PMID- 22130783
TI  - Augmented reality navigation system for laparoscopic splenectomy in children
      based on preoperative CT image using optical tracking device.
AB  - PURPOSE: In endoscopic surgery, limited views and lack of tactile sensation
      restrict the surgeon's abilities and cause stress to the surgeon. Therefore, an
      intra-operative navigation system is strongly recommended. We developed an
      augmented reality (AR) navigation system based on preoperative CT imaging. The
      purpose of this study is to evaluate the usefulness, feasibility, and accuracy of
      this system using laparoscopic splenectomy in children. METHODS: Volume images
      were reconstructed by three-dimensional (3D) viewer application. We used an
      optical tracking system for registration between volume image and body surface
      markers. The AR visualization was superimposed preoperative 3D CT images onto
      captured laparoscopic live images. This system was applied to six cases of
      laparoscopic splenectomy in children. To evaluate registration accuracy,
      distances from the marker position to the volume data were calculated. RESULTS:
      The operator recognized the hidden vascular variation of the splenic artery and
      vein, accessory spleen, and pancreatic tail by overlaying an image onto a
      laparoscopic live image. The registration accuracy of six cases was 5.30 +/-
      0.08, 5.71 +/- 1.70, 10.1 +/- 0.60, 18.8 +/- 3.56, 4.06 +/- 1.71, and 7.05 +/-
      4.71. CONCLUSION: This navigation system provides real-time anatomical
      information, which cannot be otherwise visualized without navigation. The
      registration accuracy was acceptable in clinical operation.

PMID- 22130784
TI  - Validation of a patient satisfaction questionnaire for services provided in
      Spanish community pharmacies.
AB  - BACKGROUND: The concept of Pharmaceutical Care (PC) is being gradually developed,
      and it's impact in health care should be measured using a quality tool.
      OBJECTIVE: The aim of this study was to describe and assess the psychometric
      properties of a patient satisfaction questionnaire (PSQ) for PC services in
      community pharmacies in Seville, Spain. It was based on a previous questionnaire
      in Spanish. METHODS: The face and content validity were assessed using the items
      of a validated questionnaire developed by Traverso et al. and adapted to the
      Seville pharmacy patient population. The PSQ was designed for use in the
      community pharmacy setting by a panel of seven pharmacists with expertise in both
      PC and questionnaire design. The result, was a 'draft PSQ' which comprised of 27
      multidimensional items, with responses recorded on a five-point 'Likert-type
      scale'. The validity and reliability of the 'final PSQ' was carried out using a
      cross-sectional and analytical study. Eighteen community pharmacies agreed to
      participate in the study. The draft PSQ was a self completion questionnaire
      distributed to patients by pharmacists following selection criteria. The survey
      response rate was assessed. The validity was determined by establishing the
      distribution of the PSQ's items and dimensions of the PSQ through factor
      analysis, and the reliability was evaluated with Cronbach's alpha coefficient
      (alpha). RESULTS: Two-hundred and twenty-three patients took part in the
      study.The factor analysis with varimax rotation established a 'final PSQ' with 24
      items over two dimensions: Medication Therapy Management (MTM) and General
      satisfaction with the pharmacy/staff and services (GSP/SS) which extracted 63.5%
      of the variance. The internal consistency by alpha was 0.964 for the PSQ and
      0.959 and 0.916 for the two dimensions, respectively. The median (mode) score for
      GSP/SS was 5.0 (5.0) and 4.0 (5.0) for MTM. The Wilcoxon-test indicated that the
      difference between these scores was statistically significant (P < 0.001).
      CONCLUSION: Our results suggest that the PSQ is a two dimensional instrument with
      psychometric properties able to assess patient satisfaction in community
      pharmacies. However, its validity and reliability need to be further confirmed in
      different PC settings and its sensitivity to measure changes in satisfaction over
      time also needs to be established.

PMID- 22130786
TI  - Alfacalcidol-supplemented raloxifene therapy has greater bone-sparing effect than
      raloxifene-alone therapy in postmenopausal Japanese women with osteoporosis or
      osteopenia.
AB  - Vitamin D insufficiency is prevalent in osteopenic and osteoporotic
      postmenopausal women. The persistent increase in circulating parathyroid hormone
      (PTH) caused by vitamin D insufficiency reduces bone density response to
      antiresorptive agents in these postmenopausal women. It is not well known whether
      administration of raloxifene might increase serum PTH secondary to the
      suppression of serum calcium in postmenopausal women with osteopenia or
      osteoporosis. We tried to assess whether raloxifene might affect serum PTH and
      whether the addition of alfacalcidol to raloxifene therapy could have favorable
      effects on bone mineral density (BMD) and bone turnover as compared to raloxifene
      alone therapy in postmenopausal Japanese women with osteoporosis or osteopenia
      (<=2.0 SD based on young Japanese women). A total of 169 subjects were randomly
      assigned to groups receiving 60 mg raloxifene (R), or 1 MUg alfacalcidol (D), or
      a combination of both (R + D) for 2 years. Serum levels of 25-hydroxyvitamin D
      [25(OH)D] were measured at randomization. The modified 'intention to treat'
      method was used. We compared the groups using a Tukey-Kramer test for changes in
      L- and TH-BMD and calcium metabolism when significant differences were found
      using one-way ANOVA. The parameters in each group during the experimental period
      were analyzed by means of paired t tests. Baseline 25(OH)D and i-PTH were 23.7
      ng/ml and 38.4 pg/ml, respectively. At 6 months, i-PTH demonstrated a significant
      increase (+21.0%) in the R-group whereas significant decreases in i-PTH were
      observed in the D-group and combination-group (-15.9 and -8.9%, respectively).
      There were significant increases in L-BMD in the R + D-group (+4.1% at 1 year and
      +4.7% at 2 years, P < 0.0001) and in the R-group (+2.9% at 1 year and +2.8% at 2
      years, P < 0.001), but the difference between the groups did not reach a
      significant level. Vitamin D status at randomization did not affect the
      subsequent BMD response in coadministration of alfacalcidol with raloxifene.
      Supplementation with alfacalcidol to raloxifene therapy demonstrates a greater
      bone-sparing effect by suppressing the secondary increment of serum PTH than when
      raloxifene is used alone.

PMID- 22130788
TI  - Predicting the cognitive states of the subjects in functional magnetic resonance
      imaging signals using the combination of feature selection strategies.
AB  - The functional magnetic resonance imaging (fMRI) provides very useful information
      about the activities from different brain areas during a task. This information
      can be used to train a classifier and predict the sensory and motor functions and
      also different mental states of the subject's brain in a particular task. Using a
      high resolution fMRI, normally the activities from many voxels are obtained with
      respect to time and not all of these voxels involve actively in a particular
      task. Here we propose a combination of feature selection strategies using an
      evolutionary computation algorithm and the support vector machines to find out
      those feature dimensions that are actively involved in representing the brain
      activities in a particular task. We show that using this lower dimensional space
      we can predict the cognitive state of the subjects in a particular task more
      accurately.

PMID- 22130787
TI  - Application of ex vivo micro-computed tomography for assessment of in vivo
      fluorescence and plain radiographic imaging for monitoring bone metastases and
      osteolytic lesions.
AB  - The intracardiac injection model is a commonly used in vivo model to test
      therapeutic response in bone metastases. However, few studies have critically
      compared the performance of different imaging methods in terms of sensitivity and
      quantitative assessment of osteolytic lesions. We performed in vivo optical and
      plain radiographic imaging of bone metastases followed by high-sensitivity ex
      vivo micro-computed tomography (micro-CT) imaging. This approach allowed for
      quantitative assessment of in vivo imaging techniques using fluorescence and
      plain radiography. Comparison of lesions detected in vivo by fluorescent optical
      imaging with ex vivo micro-CT revealed that the limited spatial resolution of
      fluorescent optical imaging may underestimate the number of bone metastases.
      Radiography was compared with micro-CT for the detection of osteolytic lesions.
      When using dichotomous yes/no grading, there was a 64% agreement in detection of
      osteolytic lesions. When subjective semiquantitative grading methods were used to
      assess the extent of osteolytic lesions, a positive association between the micro
      CT grades and the square root of the radiography-based grades was observed (p <
      0.05). Micro-CT also showed a significant association with fluorescent optical
      values; however, no such association was observed between lesion scores based on
      radiographs and those based on fluorescent imaging. The findings reveal an
      approximate two-fold sensitivity for micro-CT compared to plain radiography in
      the detection of osteolytic lesions. Significant associations between micro-CT
      based osteolytic lesion grade and tumor growth characterized by increased
      fluorescent area document the value of these two techniques for the assessment of
      osteolytic bone metastases.

PMID- 22130789
TI  - Influence of some formulation variables on the optimization of pH-dependent,
      colon-targeted, sustained-release mesalamine microspheres.
AB  - The aim of this work was to understand the influence of different formulation
      variables on the optimization of pH-dependent, colon-targeted, sustained-release
      mesalamine microspheres prepared by O/O emulsion solvent evaporation method,
      employing pH-dependent Eudragit S and hydrophobic pH-independent ethylcellulose
      polymers. Formulation variables studied included concentration of Eudragit S in
      the internal phase and the ratios between; internal to external phase, drug to
      Eudragit S and Eudragit S to ethylcellulose to mesalamine. Prepared microspheres
      were evaluated by carrying out in vitro release studies and determination of
      particle size, production yield, and encapsulation efficiency. In addition,
      morphology of microspheres was examined using optical and scanning electron
      microscopy. Emulsion solvent evaporation method was found to be sensitive to the
      studied formulation variables. Particle size and encapsulation efficiency
      increased by increasing Eudragit S concentration in the internal phase, ratio of
      internal to external phase, and ratio of Eudragit S to the drug. Employing
      Eudragit S alone in preparation of the microspheres is only successful in forming
      acid-resistant microspheres with pulsatile release pattern at high pH. Eudragit S
      and ethylcellulose blend microspheres were able to control release under acidic
      condition and to extend drug release at high pH. The stability studies carried
      out at 40 degrees C/75% RH for 6 months proved the stability of the optimized
      formulation. From the results of this investigation, microencapsulation of
      mesalamine in microspheres using blend of Eudragit S and ethylcellulose could
      constitute a promising approach for site-specific and controlled delivery of drug
      in colon.

PMID- 22130791
TI  - Total synthesis of the monoterpenoid alkaloid (+/-)-tangutorine.
AB  - A novel approach to a formal total synthesis of the monoterpenoid indole alkaloid
      (+/-)-tangutorine has been developed starting from an alpha,beta-unsaturated
      cyclic dehydroamino ester. Synthesis of the rather unusual trans-substituted 2,3
      indoloquinolizidine substructure was accomplished via Cu(II)-mediated conjugate
      addition and organozinc/copper coupling as the key steps, thereby setting the
      stage for ring-closing metathesis to produce the quinolone substructure. Finally,
      Bischler-Napieralski cyclization gave rise to the pentacyclic system of (+/-)
      tangutorine thereby realizing a formal synthesis in an overall yield of 5.2% in
      eight consecutive steps.

PMID- 22130790
TI  - Preparation and evaluation of dermal delivery system of griseofulvin containing
      vitamin E-TPGS as penetration enhancer.
AB  - Griseofulvin, an antifungal agent, is a BCS class II drug slowly, erratically,
      and incompletely absorbed from the gastrointestinal tract in humans. The clinical
      failure of the conventional oral therapy of griseofulvin is most likely
      attributed to its poor solubility and appreciable inter- and intra-subject
      variation in bioavailability from different commercial products. Moreover, the
      conventional oral therapy is associated with numerous adverse effects and
      interactions with other drugs. The purpose of the study was to formulate a
      topical application of griseofulvin which would deliver the drug locally in a
      therapeutically effective concentration. Griseofulvin was solubilized in ethanol,
      D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), and combinations of
      ethanol with varying amounts of TPGS; then, it was incorporated in the Carbopol
      (980 NF) base. The formulations were characterized and evaluated ex vivo using
      Laca mice skin, microbiologically against Microsporum gypseum and Microsporum
      canis and clinically in a small group of patients. The current study suggested
      that TPGS and ethanol synergistically enhanced the drug permeation and drug
      retention in the skin. The selected formulation F VII was found to be effective
      against M. gypseum and M. canis, non-sensitizing, histopathologically safe,
      stable at 4 degrees C, 25 degrees C, and 40 degrees C with respect to percent
      drug content, permeation characteristics, pH, transparency, feel, viscosity, and
      clinically effective in a small group of subjects. The proposed topical
      formulation of griseofulvin may be an effective and convenient alternative to the
      currently available oral therapy for the treatment of superficial fungal
      infections.

PMID- 22130792
TI  - Treatment of amiodarone-induced thyrotoxicosis type 2: a randomized clinical
      trial.
AB  - CONTEXT: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in
      nature, but most physicians are reluctant to continue amiodarone. When prednisone
      fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2,
      perchlorate (ClO(4)) might be useful because ClO(4) reduces the cytotoxic effect
      of amiodarone on thyrocytes. OBJECTIVES: Our objectives were to demonstrate the
      feasibility of continuation of amiodarone in AIT type 2 and to evaluate the
      usefulness of ClO(4) (given alone or in combination with prednisone) in AIT type
      2. DESIGN AND SETTING: A randomized multicenter study was conducted in 10 Dutch
      hospitals. METHODS: Patients with AIT type 2 were randomized to receive
      prednisone 30 mg/d (group A, n = 12), sodium perchlorate 500 mg twice daily
      (group B, n = 14), or prednisone plus perchlorate (group C, n = 10); all patients
      continued amiodarone and were also treated with methimazole 30 mg/d. Follow-up
      was 2 yr. MAIN OUTCOME MEASURES: Treatment efficacy (defined as TSH values >= 0.4
      mU/liter under continuation of amiodarone) and recurrent thyrotoxicosis were
      evaluated. RESULTS: Initial therapy was efficacious in 100, 71, and 100% of
      groups A, B, and C, respectively (P = 0.03). The 29% failures in group B became
      euthyroid after addition of prednisone. Neither the time to reach TSH of 0.4
      mU/liter or higher [8 wk (4-20), 14 wk (4-32), and 12 wk (4-28) in groups A, B,
      and C respectively] nor the time to reach free T(4) of 25 pmol/liter or below [4
      wk (4-20), 12 wk (4-20), and 8 wk (4-20) in groups A, B, and C) were
      significantly different between groups (values as median with range). Recurrent
      thyrotoxicosis occurred in 8.3%. CONCLUSION: Euthyroidism was reached despite
      continuation of amiodarone in all patients. Prednisone remains the preferred
      treatment modality of AIT type 2, because perchlorate given alone or in
      combination with prednisone had no better outcomes.

PMID- 22130793
TI  - Severe short stature caused by novel compound heterozygous mutations of the
      insulin-like growth factor 1 receptor (IGF1R).
AB  - CONTEXT: IGF-I, essential for normal human growth in utero and postnatally,
      mediates its effects through the IGF-I receptor (IGF1R). More than nine
      heterozygous mutations, including one compound heterozygous mutation, of the
      IGF1R gene have been reported in patients with varying degrees of intrauterine
      and postnatal growth retardation. OBJECTIVE: The objective of the study was the
      analysis of the IGF1R gene in a short-statured patient. PATIENT: The male
      patient, with a height of -5.91 sd score (aged 20.3 yr), had consistently
      elevated circulating serum concentrations of IGF-I. A diagnosis of antibody
      negative insulin-requiring diabetes was made at age 14 yr. His deceased sister
      was also severely short statured (-3.75 sd score). RESULTS: The patient and his
      sister carried novel, compound heterozygous IGF1R missense mutations, E121K (exon
      2) and E234K (exon 3), inherited from the mother and father, respectively. In
      vitro reconstitution studies demonstrated that neither the E121K nor E234K
      mutation affected IGF1R prepeptide expression, but levels of the proteolytically
      cleaved alpha- and beta-subunit were consistently low. As a consequence, each
      IGF1R variant exhibited significantly reduced IGF-I-induced signal transduction.
      Correlating to these studies, expression of functional IGF1R and the IGF-I
      induced activation of the IGF1R pathway were markedly reduced in the primary
      dermal fibroblasts established from the patient. CONCLUSIONS: Only the second
      compound heterozygous IGF1R mutations to be identified, the p.E121K/E234K variant
      is the cause of intrauterine growth retardation and the most severe postnatal
      growth failure described to date in a patient with IGF1R defects. Whether the
      mutant IGF1R also contributes to the diabetic phenotype, however, remains to be
      determined.

PMID- 22130794
TI  - Localization and retention of p90 ribosomal S6 kinase 1 in the nucleus:
      implications for its function.
AB  - Ribosomal S6 kinase 1 (RSK1) belongs to a family of proteins with two kinase
      domains. Following activation in the cytoplasm by extracellular signal-regulated
      kinases (ERK1/2), it mediates the cell-proliferative, cell-growth, and survival
      promoting actions of a number of growth factors and other agonists. These diverse
      biological actions of RSK1 involve regulation of both cytoplasmic and nuclear
      events. However, the mechanisms that permit nuclear accumulation of RSK1 remain
      unknown. Here, we show that phosphorylation of RSK1 on S221 is important for its
      dissociation from the type Ialpha regulatory subunit of protein kinase A (PKA) in
      the cytoplasm and that RSK1 contains a bipartite nuclear localization sequence
      that is necessary for its nuclear entry. Once inside, the active RSK1 is retained
      in the nucleus via its interactions with PKA catalytic subunit and AKAP95.
      Mutations of RSK1 that do not affect its activity but disrupt its entry into the
      nucleus or expression of AKAP95 forms that do not enter the nucleus inhibit the
      ability of active RSK1 to stimulate DNA synthesis. Our findings identify novel
      mechanisms by which active RSK1 accumulates in the nucleus and also provide new
      insights into how AKAP95 orchestrates cell cycle progression.

PMID- 22130795
TI  - Subtelomere-binding protein Tbf1 and telomere-binding protein Rap1 collaborate to
      inhibit localization of the Mre11 complex to DNA ends in budding yeast.
AB  - Chromosome ends, known as telomeres, have to be distinguished from DNA double
      strand breaks that activate DNA damage checkpoints. In budding yeast, the Mre11
      Rad50-Xrs2 (MRX) complex associates with DNA ends and promotes checkpoint
      activation. Rap1 binds to double-stranded telomeric regions and recruits Rif1 and
      Rif2 to telomeres. Rap1 collaborates with Rif1 and Rif2 and inhibits MRX
      localization to DNA ends. This Rap1-Rif1-Rif2 function becomes attenuated at
      shortened telomeres. Here we show that Rap1 acts together with the subtelomere
      binding protein Tbf1 and inhibits MRX localization to DNA ends. The placement of
      a subtelomeric sequence or TTAGGG repeats together with a short telomeric TG
      repeat sequence inhibits MRX accumulation at nearby DNA ends in a Tbf1-dependent
      manner. Moreover, tethering of both Tbf1 and Rap1 proteins decreases MRX and Tel1
      accumulation at nearby DNA ends. This Tbf1- and Rap1-dependent pathway operates
      independently of Rif1 or Rif2 function. Depletion of Tbf1 protein stimulates
      checkpoint activation in cells containing short telomeres but not in cells
      containing normal-length telomeres. These data support a model in which Tbf1 and
      Rap1 collaborate to maintain genomic stability of short telomeres.

PMID- 22130796
TI  - Timing of centrosome separation is important for accurate chromosome segregation.
AB  - Spindle assembly, establishment of kinetochore attachment, and sister chromatid
      separation must occur during mitosis in a highly coordinated fashion to ensure
      accurate chromosome segregation. In most vertebrate cells, the nuclear envelope
      must break down to allow interaction between microtubules of the mitotic spindle
      and the kinetochores. It was previously shown that nuclear envelope breakdown
      (NEB) is not coordinated with centrosome separation and that centrosome
      separation can be either complete at the time of NEB or can be completed after
      NEB. In this study, we investigated whether the timing of centrosome separation
      affects subsequent mitotic events such as establishment of kinetochore attachment
      or chromosome segregation. We used a combination of experimental and
      computational approaches to investigate kinetochore attachment and chromosome
      segregation in cells with complete versus incomplete spindle pole separation at
      NEB. We found that cells with incomplete spindle pole separation exhibit higher
      rates of kinetochore misattachments and chromosome missegregation than cells that
      complete centrosome separation before NEB. Moreover, our mathematical model
      showed that two spindle poles in close proximity do not "search" the entire
      cellular space, leading to formation of large numbers of syntelic attachments,
      which can be an intermediate stage in the formation of merotelic kinetochores.

PMID- 22130797
TI  - Punctuated cyclin synthesis drives early embryonic cell cycle oscillations.
AB  - Cyclin B activates cyclin-dependent kinase 1 (CDK1) at mitosis, but conflicting
      views have emerged on the dynamics of its synthesis during embryonic cycles,
      ranging from continuous translation to rapid synthesis during mitosis. Here we
      show that a CDK1-mediated negative-feedback loop attenuates cyclin production
      before mitosis. Cyclin B plateaus before peak CDK1 activation, and proteasome
      inhibition caused minimal accumulation during mitosis. Inhibiting CDK1 permitted
      continual cyclin B synthesis, whereas adding nondegradable cyclin stalled it.
      Cycloheximide treatment before mitosis affected neither cyclin levels nor mitotic
      entry, corroborating this repression. Attenuated cyclin production collaborates
      with its destruction, since excess cyclin B1 mRNA accelerated cyclin synthesis
      and caused incomplete proteolysis and mitotic arrest. This repression involved
      neither adenylation nor the 3' untranslated region, but it corresponded with a
      shift in cyclin B1 mRNA from polysome to nonpolysome fractions. A pulse-driven
      CDK1-anaphase-promoting complex (APC) model corroborated these results, revealing
      reduced cyclin levels during an oscillation and permitting more effective
      removal. This design also increased the robustness of the oscillator, with
      lessened sensitivity to changes in cyclin synthesis rate. Taken together, the
      results of this study underscore that attenuating cyclin synthesis late in
      interphase improves both the efficiency and robustness of the CDK1-APC
      oscillator.

PMID- 22130798
TI  - Trisomy 12 and elevated GLI1 and PTCH1 transcript levels are biomarkers for
      Hedgehog-inhibitor responsiveness in CLL.
AB  - Hedgehog (HH) signaling is activated in various lymphoid malignancies, but
      conflicting results exist about its role in chronic lymphocytic leukemia (CLL).
      Here, we demonstrate that the expression of essential HH pathway components like
      GLI1, PTCH1, and the HH ligands is highly diverse in CLL. A subset of 36.7% of 60
      tested CLL samples responded to all 3 SMOOTHENED (SMO) inhibitors, whereas 40%
      were completely resistant. Responsiveness correlated with elevated GLI1 and PTCH1
      transcript levels and the presence of trisomy 12, whereas no other karyotype
      correlated with responsiveness. All trisomy 12 CLLs displayed constitutive HH
      pathway activation driven by autocrine DESERT HH (DHH) ligand secretion, which
      could be blocked by the HH-blocking Ab 5E1. Cocultures with DHH-expressing BM
      stromal cells reduced sensitivity of CLLs to SMO-inhibitor treatment by
      activation of noncanonical ERK phosphorylation directly downstream of the PTCH1
      receptor without involvement of SMO and could be overcome by the HH-blocking Ab
      5E1 or a combination of SMO and ERK inhibitors. Our results demonstrate that the
      HH-signaling pathway is an interesting therapeutic target for a subset of
      patients with CLL, characterized by high GLI1 and PTCH1 transcript levels, and
      all patients with trisomy 12 and indicate HH-blocking Abs to be favorable over
      SMO inhibitors in overcoming stroma-mediated protective effects.

PMID- 22130799
TI  - IFN-gamma and indoleamine 2,3-dioxygenase signaling between donor dendritic cells
      and T cells regulates graft versus host and graft versus leukemia activity.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) can eradicate
      chemorefractory leukemia through the graft-versus-leukemia (GVL) activity of
      donor T cells. However, the clinical success of allo-HSCT is limited by the graft
      versus-host disease (GVHD) activity of donor T cells. We have reported previously
      that donor bone marrow precursors of plasmacytoid dendritic cells (pre-pDCs) can
      activate donor T cells toward T-helper 1 immune polarization in murine allogeneic
      HSCT. To optimize the GVL activity of these activated donor T cells and limit
      their graft versus host activity, we engineered the cellular constituents of an
      allogeneic hematopoietic stem cell graft with highly purified hematopoietic stem
      cells, T cells, and pre-pDCs and studied their GVL and GVHD activities in a
      murine model of allogeneic HSCT. Transplanted donor pre-pDCs expanded in vivo for
      2 weeks after transplant, and they markedly augmented the activation and GVL
      activity of donor T cells while attenuating their GVHD activity, leading to an
      improved therapeutic index. Bidirectional signaling between donor T cells and
      donor pDCs with IFN-gamma synthesis by donor T cells inducing indoleamine 2,3
      dioxygenase synthesis by donor pDCs limited GVHD by altering the balance between
      donor T-reg and inflammatory T cells. Manipulating the content of donor DC
      precursors in allogeneic HSCT is a novel method to optimize the balance between
      GVL and GVHD.

PMID- 22130800
TI  - Vitamin K antagonists in children with heart disease: height and VKORC1 genotype
      are the main determinants of the warfarin dose requirement.
AB  - Managing vitamin K antagonist (VKA) therapy is challenging in children because of
      a narrow therapeutic range and wide inter- and intra-individual variability in
      dose response. Only a few small studies have investigated the effect of
      nongenetic and genetic factors on the dose response to VKAs in children. In a
      cohort study including 118 children (median age 9 years; range, 3 months-18
      years) mostly with cardiac disease, we evaluated by multivariate analysis the
      relative contribution of nongenetic factors and VKORC1/CYP2C9/CYP4F2 genotypes on
      warfarin (n = 83) or fluindione (n = 35) maintenance dose and the influence of
      these factors on the time spent within/above/below the range. The results showed
      that height, target international normalized ratio and VKORC1 and CYP2C9
      genotypes were the main determinants of warfarin dose requirement, accounting for
      48.1%, 4.4%, 18.2%, and 2.0% of variability, respectively, and explaining 69.7%
      of the variability. Our model predicted the warfarin dose within 7 mg/wk in 86.7%
      of patients. None of the covariates was associated with the time spent above or
      below the international normalized ratio range. Whether this model predicts
      accurately the effective maintenance dose is currently being investigated.

PMID- 22130801
TI  - Regulation of hepcidin expression at high altitude.
AB  - Enhanced erythropoietic drive and iron deficiency both influence iron homeostasis
      through the suppression of the iron regulatory hormone hepcidin. Hypoxia also
      suppresses hepcidin through a mechanism that is unknown. We measured iron indices
      and plasma hepcidin levels in healthy volunteers during a 7-day sojourn to high
      altitude (4340 m above sea level), with and without prior intravenous iron
      loading. Without prior iron loading, a rapid reduction in plasma hepcidin was
      observed that was almost complete by the second day at altitude. This occurred
      before any index of iron availability had changed. Prior iron loading delayed the
      decrease in hepcidin until after the transferrin saturation, but not the ferritin
      concentration, had normalized. We conclude that hepcidin suppression by the
      hypoxia of high altitude is not driven by a reduction in iron stores.

PMID- 22130802
TI  - Neonatal screening for severe primary immunodeficiency diseases using high
      throughput triplex real-time PCR.
AB  - Severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) are
      inborn errors of immune function that require prompt diagnosis and treatment to
      prevent life-threatening infections. The lack of functional T or B lymphocytes in
      these diseases serves as a diagnostic criterion and can be applied to neonatal
      screening. A robust triplex PCR method for quantitation of T-cell receptor
      excision circles (TRECs) and kappa-deleting recombination excision circles
      (KRECs), using a single Guthrie card punch, was developed and validated in a
      cohort of 2560 anonymized newborn screening cards and in 49 original stored
      Guthrie cards from patients diagnosed with SCID, XLA, ataxia-telangiectasia,
      Nijmegen-breakage-syndrome, common variable immunodeficiency, immunoglobulin A
      deficiency, or X-linked hyper-IgM syndrome. Simultaneous measurement of TREC and
      KREC copy numbers in Guthrie card samples readily identified patients with SCID,
      XLA, ataxia-telangiectasia and Nijmegen-breakage-syndrome and thus facilitates
      effective newborn screening for severe immunodeficiency syndromes characterized
      by the absence of T or B cells.

PMID- 22130803
TI  - Expansion of functionally defined mouse hematopoietic stem and progenitor cells
      by a short isoform of RUNX1/AML1.
AB  - Self-renewal activity is essential for the maintenance and regeneration of the
      hematopoietic system. The search for molecules capable of promoting self-renewal
      and expanding hematopoietic stem cells (HSCs) has met with limited success. Here,
      we show that a short isoform (AML1a) of RUNX1/AML1 has such activities. Enforced
      AML1a expression expanded functionally defined HSCs, with an efficiency that was
      at least 20 times greater than that of the control in vivo and by 18-fold within
      7 days ex vivo. The ex vivo-expanded HSCs could repopulate hosts after secondary
      transplantations. Moreover, AML1a expression resulted in vigorous and long-term
      (> 10(6)-fold at 4 weeks) ex vivo expansion of progenitor cell populations
      capable of differentiating into multilineages. Gene expression analysis revealed
      that AML1a expression was associated with up-regulation of genes, including
      Hoxa9, Meis1, Stat1, and Ski. shRNA-mediated silencing of these genes attenuated
      AML1a-mediated activities. Overall, these findings establish AML1a as an isoform
      specific molecule that can influence several transcriptional regulators
      associated with HSCs, leading to enhanced self-renewal activity and hematopoietic
      stem/progenitor cell expansion ex vivo and in vivo. Therefore, the abilities of
      AML1a may have implications for HSC transplantation and transfusion medicine,
      given that the effects also can be obtained by cell-penetrating AML1a protein.

PMID- 22130805
TI  - Osteoarthritis as an autoinflammatory disease caused by chondrocyte-mediated
      inflammatory responses.

PMID- 22130804
TI  - Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the
      progression of pneumococcal disease by down-modulating E-selectin.
AB  - Sickle cell anemia is characterized by chronic hemolysis coupled with extensive
      vascular inflammation. This inflammatory state also mechanistically promotes a
      high risk of lethal, invasive pneumococcal infection. Current treatments to
      reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce
      fetal hemoglobin. Because hydroxyurea also reduces leukocytosis, an understanding
      of the impact of this treatment on pneumococcal pathogenesis is needed. Using a
      sickle cell mouse model of pneumococcal pneumonia and sepsis, administration of
      hydroxyurea was found to significantly improve survival. Hydroxyurea treatment
      decreased neutrophil extravasation into the infected lung coincident with
      significantly reduced levels of E-selectin in serum and on pulmonary epithelia.
      The protective effect of hydroxyurea was abrogated in mice deficient in E
      selectin. The decrease in E-selectin levels was also evident in human sickle cell
      patients receiving hydroxyurea therapy. These data indicate that in addition to
      induction of fetal hemoglobin, hydroxyurea attenuates leukocyte-endothelial
      interactions in sickle cell anemia, resulting in protection against lethal
      pneumococcal sepsis.

PMID- 22130806
TI  - Does venous insufficiency impair the exercise-induced rise in arterial leg blood
      flow? And what does it mean for clinical phlebology?

PMID- 22130807
TI  - Designing a research study.

PMID- 22130808
TI  - Intraoperative ultrasound.

PMID- 22130810
TI  - Letter regarding 'The role of perforators in chronic venous insufficiency' by T F
      O'Donnell. Phlebology 2010;25:3-10.

PMID- 22130812
TI  - A decade of achievement in pulmonary hypertension.

PMID- 22130813
TI  - Systemic lupus erythematosus-associated PAH: is targeting inflammation the key to
      success?

PMID- 22130814
TI  - A tribute: Abel Ayerza and pulmonary hypertension.

PMID- 22130815
TI  - The value of tools to assess pulmonary arterial hypertension.
AB  - Pulmonary hypertension is a common but complex clinical problem. When suspected
      in an appropriate clinical setting or detected incidetally, an array of
      investigative tools are employed with an intent to confirm the diagnosis, define
      aetiology, evaluate the functional and haemodynamic impairment, define treatment
      options, monitor the therapy, and establish long-term prognosis. However, no
      single tool provides comprehensive information that encompasses the
      aforementioned aims. Therefore, judicious use of these tools is of paramount
      importance, in order to maximise outcome and cost-effectiveness, while minimising
      risks and redundancies. Furthermore, a number of promising tools and techniques
      are emerging rapidly in the arena of pulmonary hypertension. These tools augment
      our understanding of pathophysiology and natural history of pulmonary
      hypertension. There is, therefore, increasing need for validating these emerging
      paradigms in multicentre trials. In this review, we focus on the tools commonly
      used to evaluate pulmonary arterial hyertension and also define some of the new
      approaches to pulmonary arterial hypertension.

PMID- 22130816
TI  - Prognostic factors in pulmonary arterial hypertension: assessing the course of
      the disease.
AB  - The practical management of pulmonary arterial hypertension (PAH) requires an
      accurate assessment of disease severity and prognosis. A number of prognostic
      indicators are known to be associated with patient outcome, and recent treatment
      guidelines advocate using such parameters to guide management decisions. Although
      PAH is characterised by the presence of pulmonary vasculopathy, it is the
      response of the right ventricle to an increased afterload that is the greatest
      determinant of a patient's symptoms and survival; thus, measurements that capture
      right ventricular function provide the best potential to assess PAH severity. One
      challenge is to understand how the tests we use in everyday clinical practice
      relate to right heart function in PAH patients, and how current measures can be
      improved and developed to optimise assessment of disease status and progress.
      Future research in the field of PAH should focus on how best to assess right
      heart function, and which measures or combination of measures provide the most
      relevant information for the individual patient.

PMID- 22130817
TI  - The role of the right ventricle in pulmonary arterial hypertension.
AB  - Although changes in the pulmonary vasculature are the primary cause of pulmonary
      arterial hypertension (PAH), severity of symptoms and survival are strongly
      associated with right ventricular function, and right heart failure is the main
      cause of death in patients with PAH. Echocardiography and cardiac magnetic
      resonance imaging allow noninvasive evaluation of right ventricular function and
      structure, and a number of indices have been shown to have potential prognostic
      value in PAH. Given the importance of the right ventricle in PAH, preservation
      and improvement of its function should be important aspects of therapy; however,
      there are currently few data specifically related to this aspect of treatment
      response. Simple, reproducible, noninvasive measures of right ventricular
      function would help to improve the management of patients with PAH, and to
      provide tools with which to help establish the optimal therapeutic approach to
      manage not only the effects of the disease on the pulmonary vasculature, but also
      to support and improve right ventricular function.

PMID- 22130818
TI  - Optimal management of severe pulmonary arterial hypertension.
AB  - Over the past decade, awareness among the medical profession of pulmonary
      arterial hypertension (PAH) being a treatable disease has increased. Despite
      this, approximately one-fifth of newly diagnosed patients are classified as being
      in the most severely compromised functional class (i.e. New York Health
      Association/World Health Organization functional class (NYHA/WHO FC) IV). The
      prognosis for patients in NYHA/WHO FC IV is poor, with 3-yr survival being around
      40%, even with treatment. Poor prognosis coupled with severe functional
      impairment means it is vital that these patients receive optimal treatment. There
      are also subgroups of patients, who, although classified as NYHA/WHO FC III, may
      actually be severely haemodynamically compromised and at risk of rapid
      deterioration. Such subgroups include patients with PAH associated with systemic
      sclerosis or certain heritable mutations. These patients should be considered as
      being at the more severe end of the disease spectrum. In this article we will
      discuss the optimal management of patients with severe PAH. This includes newly
      emerging evidence from small-scale, open-label studies that use upfront
      combination therapy with intravenous epoprostenol plus oral PAH-specific drugs.
      We also review treatment strategies that may offer clinical benefits to patients
      with more severe PAH.

PMID- 22130819
TI  - Looking to the future: a new decade of pulmonary arterial hypertension therapy.
AB  - Pulmonary arterial hypertension (PAH) is a severe and debilitating disease
      characterised by vascular proliferation and remodelling of the small pulmonary
      arteries, leading to a progressive increase in pulmonary vascular resistance,
      increased afterload on the right ventricle and, ultimately, right heart failure.
      Although there is no "cure" for PAH, the availability of targeted therapies over
      the past decade has led to major advances in the management of PAH, reflected in
      improvements in survival in the modern treatment era. However, despite this,
      disease progression is inevitable in the majority of patients with PAH and
      overall the long-term prognosis, although improved, remains poor. There is a
      clear and urgent need for new therapeutic options, either through the development
      of improved drugs that act on targets established by existing PAH-specific
      therapies, or of agents targeting novel pathogenic pathways not addressed by
      currently available therapies. A number of such new agents that have shown
      promise in experimental models and preliminary human studies are discussed in
      this article.

PMID- 22130820
TI  - Risk factors associated with pulmonary arterial hypertension in patients with
      systemic sclerosis and implications for screening.
AB  - Pulmonary arterial hypertension (PAH) is a relatively common complication of
      systemic sclerosis (SSc) affecting 5-12% of patients, and its development is
      associated with significant morbidity and a particularly poor prognosis. Deaths
      associated with other complications of SSc, such as renal crisis, have fallen
      significantly in recent years in line with improvements in their treatment and
      management. However, mortality due to PAH in this population, although improved,
      has shown a less dramatic decline. The early diagnosis of PAH in SSc would allow
      for earlier treatment, before functional and haemodynamic impairment becomes
      severe; this may further improve outcome, and evidence suggests that screening of
      SSc patients for PAH is associated with improved survival. In addition, patients
      with PAH associated with SSc are not a homogeneous population and they differ in
      terms of disease haemodynamic severity, functional capacity and rate of disease
      progression. Likewise, management strategies may differ, and the ability to
      stratify patients may help optimise screening and treatment. A number of patient
      , clinical- and disease-specific risk factors associated with the development and
      prognosis of PAH in SSc have been identified, but their optimal use, alone or in
      combination, in screening and stratification of patients remains to be
      established.

PMID- 22130821
TI  - Pulmonary hypertension in systemic sclerosis and systemic lupus erythematosus.
AB  - Pulmonary arterial hypertension (PAH) is a severe manifestation of systemic
      sclerosis (SSc) and systemic lupus erythematosus (SLE). Due to improvements in
      the understanding of the pathogenesis of these diseases, improved methodological
      rigour in the conduct of epidemiological studies and the advent of successful
      therapies, our understanding of SSc-PAH and SLE-PAH has evolved considerably. In
      this review we will review the current evidence regarding the prevalence,
      prognostic factors and survival estimates for SSc-PAH and SLE-PAH. In doing so,
      we will compare and contrast these two diseases, highlight clinically useful
      features, discuss methodological limitations of existing data, and draw attention
      to areas where research is needed.

PMID- 22130822
TI  - Asthma and suicide-related adverse events: a review of observational studies.
AB  - Suicide is a major public health concern. There are several risk factors
      associated with suicide. Chronic illnesses, such as asthma, have been linked to
      an increased risk of suicide-related events. This study reviews the evidence of
      an association between asthma and suicide using published epidemiological
      observational studies. An electronic search using PubMed and EMBASE was
      performed. Studies that investigated the association of asthma with suicide
      related behaviour were selected. Studies were examined to form a descriptive
      analysis. Six observational studies met the selection criteria, of which at least
      one suicide-related adverse event was studied. Three studies investigated
      completed suicide, two suicide attempts and four suicide ideation. Two of the
      studies focused on individuals aged <18 yrs. Evidence from observational data
      support the hypothesis of an association between asthma and suicide-related
      behaviour (ideation, attempts and completion); however, epidemiological studies,
      with more objective measures and larger sample sizes, adjusting for a wider scope
      of suicide-related confounding factors (e.g. comorbidities), and with a
      longitudinal design, are needed for a more conclusive answer.

PMID- 22130823
TI  - The management of Eisenmenger syndrome in the modern treatment era: a case
      report.

PMID- 22130824
TI  - "Treat-to-target" in pulmonary arterial hypertension and the use of
      extracorporeal membrane oxygenation as a bridge to transplantation.

PMID- 22130825
TI  - Drug-induced eosinophilic pleural effusion.

PMID- 22130826
TI  - A double-blind placebo-controlled trial to study therapeutic effects of probiotic
      Escherichia coli Nissle 1917 in subgroups of patients with irritable bowel
      syndrome.
AB  - PURPOSE: To study the therapeutic effects of probiotic Escherichia coli Nissle
      1917 (EcN) in irritable bowel syndrome (IBS) and identify subgroups benefiting
      most. BACKGROUND: Some trials investigating therapeutic effects in irritable
      bowel syndrome have shown benefits in IBS subgroups only. Probiotic treatment
      seems to be promising. METHODS: Patients with irritable bowel syndrome (120; Rome
      II) were recruited to a prospective double-blind study and randomized to either
      EcN (n = 60) or placebo (n = 60) given for 12 weeks. Objectives were to describe
      efficacy and safety of EcN in different groups of irritable bowel syndrome.
      Outcome was assessed by 'Integrative Medicine Patient Satisfaction Scale'.
      RESULTS: Altogether, the responder rate was higher in the EcN than in the placebo
      group. However, only after 10 and 11 weeks, the differences were significant
      (Delta 20.0% points [95% CI 2.6; 37.4], p = 0.01 and Delta 18.3% points [95% CI
      1.0; 35.7], p = 0.02, respectively). The best response was observed in the
      subgroup of patients with gastroenteritis or antibiotics prior to irritable bowel
      syndrome onset (Delta 45.7% points, p = 0.029). No significant differences were
      observed in any other subgroup. Both treatment groups showed similar adverse
      events and tolerance. CONCLUSIONS: Probiotic EcN shows effects in irritable bowel
      syndrome, especially in patients with altered enteric microflora, e.g. after
      gastroenterocolitis or administration of antibiotics.

PMID- 22130827
TI  - Percutaneous gastrostomy tubes in children with Pierre Robin sequence: efficacy,
      maintenance and complications.
AB  - BACKGROUND: Children with Pierre Robin sequence (PRS) have significant
      oropharyngeal abnormalities, with respiratory and feeding difficulties.
      Gastrostomy tubes (G-tube) provide a means for nutrition. OBJECTIVE: To evaluate
      the safety and efficacy of percutaneous G-tube insertion in children with PRS.
      MATERIALS AND METHODS: Of 120 children with PRS (1996-2009), 40 were referred for
      G-tube insertion; clinical details were reviewed in 37/40 children (18M, 19F) at
      three time periods: (1) pre-G-tube insertion, (2) at G-tube insertion, (3) at G
      tube removal. RESULTS: Pre-G-tube: 32/37 were term infants; 5 were preterm; 16/37
      children were <= 10th weight percentile. At G-tube insertion, mean age was 66
      days, mean weight 4.4 kg (1.1-7.0 kg); 19 dropped >=10 weight percentiles; 12
      tolerated nil by mouth; 2/37 were intubated for the procedure. All G-tubes were
      successfully placed, with five minor technical issues. Early postprocedure, there
      were eight minor complications and two dislodgements (classified as major). At G
      tube removal mean G-tube dwell time was 2 years, with an average of 3.6
      maintenance procedures per child, approximately 3 tube changes/1,000 tube days.
      At G-tube removal, 76% had maintained or increased weight centiles. CONCLUSION: G
      tubes in PRS provide a safe method for nutrition until children feed adequately
      by mouth.

PMID- 22130828
TI  - Isolation and characterization of human fetal myoblasts.
AB  - Dissociated human fetal skeletal muscle contains myogenic cells, as well as non
      myogenic cells such as adipocytes, fibroblasts, and lymphocytes. It is therefore
      important to determine an efficient and reliable isolation method to obtain a
      purer population of myoblasts. Toward this end, fluorescence-activated cell
      sorting in conjunction with robust myogenic cell surface markers can be utilized
      to enrich for myoblasts in dissociated muscle. In this chapter, we describe a
      method to significantly enrich for myoblasts using -melanoma cell adhesion
      molecule (MCAM), which we have determined to be an excellent marker of human
      fetal myoblasts. The myoblasts resulting from this isolation method can then be
      expanded in vitro and still retain significant myogenic activity as shown by an
      in vitro fusion assay. The ability to isolate a highly myogenic population from
      dissociated muscle facilitates the in vitro study of skeletal muscle development
      and muscle diseases. Furthermore, robust expansion of these cells will lead to
      new insights in the development of cell-based therapies for human muscle
      disorders.

PMID- 22130830
TI  - Isolation of muscle stem cells by fluorescence activated cell sorting cytometry.
AB  - Satellite cells are a heterogeneous population of muscle progenitors with stem
      cell properties responsible for the regeneration of adult skeletal muscle.
      Increasing interest in the therapeutic potential of satellite cells has
      challenged researchers with the need to purify a homogenous population of muscle
      progenitors. Here we provide a detailed protocol for the isolation of a pure
      population of satellite cells using fluorescence activated cell sorting. We give
      specific guidelines to ameliorate the reproducibility of the satellite cell
      isolation protocol with the goal to standardize procedures across labs. This
      protocol identifies satellite cells within adult skeletal muscle as an enriched
      population of Integrin alpha7(+)/CD34(+) double positive cells and CD45, CD31,
      CD11b, and Sca1 negative (Lin(-)) cells (Integrin alpha7(+)/CD34(+)/Lin(-)).
      Functional assay shows that Integrin alpha7(+)/CD34(+)/Lin(-) satellite cells
      possess high myogenic potential and ability to regenerate muscle depleted
      satellite cells upon transplantation.

PMID- 22130829
TI  - Skeletal muscle satellite cells: background and methods for isolation and
      analysis in a primary culture system.
AB  - Repair of adult skeletal muscle depends on satellite cells, myogenic stem cells
      located between the basal lamina and the plasmalemma of the myofiber.
      Standardized protocols for the isolation and culture of satellite cells are key
      tools for understanding cell autonomous and extrinsic factors that regulate their
      performance. Knowledge gained from such studies can contribute important insights
      to developing strategies for the improvement of muscle repair following trauma
      and in muscle wasting disorders. This chapter provides an introduction to
      satellite cell biology and further describes the basic protocol used in our
      laboratory to isolate and culture satellite cells from adult skeletal muscle. The
      cell culture conditions detailed herein support proliferation and differentiation
      of satellite cell progeny and the development of reserve cells, which are thought
      to reflect the in vivo self-renewal ability of satellite cells. Additionally,
      this chapter describes our standard immunostaining protocol that allows the
      characterization of satellite cell progeny by the temporal expression of
      characteristic transcription factors and structural proteins associated with
      different stages of myogenic progression. Although emphasis is given here to the
      isolation and characterization of satellite cells from mouse hindlimb muscles,
      the protocols are suitable for other muscle types (such as diaphragm and
      extraocular muscles) and for muscles from other species, including chicken and
      rat. Altogether, the basic protocols described are straightforward and facilitate
      the study of diverse aspects of skeletal muscle stem cells.

PMID- 22130831
TI  - Mouse and human mesoangioblasts: isolation and characterization from adult
      skeletal muscles.
AB  - Mesoangioblasts (MABs) are mesoderm-derived stem cells, associated with small
      vessels and originally described in the mouse embryonic dorsal aorta. Similar
      though not identical cells have been later identified and characterized from
      postnatal small vessels of skeletal muscle and heart. They have in common the
      expression of pericyte markers, the anatomical location, the ability to self
      renew in culture, and to differentiate into various types of mesodermal lineages
      upon proper culture conditions. Currently, the developmental origin of MABs and
      the relationship with other muscle stem cells are not understood in detail and
      are the subject of active research. This chapter provides an outline of the
      latest techniques for isolation and characterization of adult MABs from human and
      mouse skeletal muscles.

PMID- 22130832
TI  - Direct electrical stimulation of myogenic cultures for analysis of muscle fiber
      type control.
AB  - Secondary skeletal muscle fiber phenotype is dependent upon depolarization from
      motor neuron innervation. To study the effects of depolarization on muscle fiber
      type development, several in vivo and in vitro model systems exist. We have
      developed a relatively simple-to-use in vitro model system in which
      differentiated muscle cells are directly electrically stimulated at precise
      frequencies. This allows for single cell analysis as well as biochemical and
      molecular analyses of the mechanisms that control skeletal muscle phenotype.

PMID- 22130833
TI  - Single muscle-fiber isolation and culture for cellular, molecular,
      pharmacological, and evolutionary studies.
AB  - The technique of single muscle-fiber cultures has already proven valuable in
      extending knowledge of myogenesis, stem cell heterogeneity, the stem cell niche
      in skeletal muscle, and satellite cell activation. This report reviews the
      background of the model and applications, and details the procedures of muscle
      dissection, fiber digestion and isolation, cleaning the fiber preparation,
      plating fibers, and extensions of the technique for studying activation from
      stable quiescence of satellite cells, mRNA expression by in situ hybridization
      and regulation of satellite cell activation in zebrafish muscle by nitric oxide,
      hepatocyte growth factor.

PMID- 22130834
TI  - Somite unit chronometry to analyze teratogen phase specificity in the paraxial
      mesoderm.
AB  - Phase specificity, the temporal and tissue restriction of teratogen-induced
      defects during embryonic -development, is a poorly understood but common property
      of teratogens, an important source of human birth defects. Somite counting and
      somite units are novel chronometric tools used here to identify stages of
      paraxial mesoderm development that are sensitive to pulse-chase exposure (2 to
      >16 h) to 5-bromodeoxyuridine (BrdU). In all cases, it was the presomitic
      mesoderm (PSM) that was sensitive to BrdU induced segmentation anomalies. At high
      concentration (1.0 * 10(-2) M BrdU), PSM presegment stages ss-IV and earlier were
      irreversibly inhibited from completing segmentation. At low concentration (2.6 *
      10(-6) M), BrdU induced periodic focal defects that predominantly trace back to
      PSM presegments between ss-V and ss-IX. Phase specificity is characteristic of
      both types of segmentation anomalies. Focal segmentation defects are phase
      specific because they result from disruption of 2-3 presegments in the PSM while
      adjacent -rostral and caudal presegments are (apparently) unaffected.
      Irreversible inhibition of segmentation is also phase-specific because only PSM
      presegments ss-IV or earlier were affected while older segments (ss-III to ss-I)
      were able to complete segmentation. The presegments predominantly affected have
      not yet passed the determination front, the point at which the segmentation clock
      establishes somite rostro-caudal -polarity. Somite unit chronometry provides a
      means to identify specific PSM presegment stages that are susceptible to induced
      segmentation defects and the biological processes that underlie that
      vulnerability.

PMID- 22130835
TI  - Analysis of skeletal muscle development in Drosophila.
AB  - The Drosophila system has been invaluable in providing important insights into
      mesoderm specification, muscle specification, myoblast fusion, muscle
      differentiation, and myofibril assembly. Here, we present a series of Drosophila
      protocols that enable the researcher to visualize muscle precursors and
      differentiated muscles, at all stages of development. In doing so, we also
      highlight the variety of techniques that are used to create these findings. These
      protocols are directly used for the Drosophila system, and are provided with
      explanatory detail to enable the researcher to apply them to other systems.

PMID- 22130836
TI  - Immunocytochemistry to study myogenesis in zebrafish.
AB  - During myogenesis, cells gradually transition from mesodermal precursors to
      myoblasts, myocytes, and then to muscle fibers. The molecular characterization of
      this process requires the ability to identify each of these cell types and the
      factors that regulate the transitions between them. The most versatile technique
      for assaying cell identities in situ is immunocytochemistry, because multiple
      independent molecular markers of differentiation can be assayed simultaneously.
      The zebrafish has developed into a popular model for the study of myogenesis, and
      immunocytochemical techniques have been critical. We have adapted existing
      protocols to optimize immunocytochemistry in zebrafish, and have tested many
      antibodies developed against mouse, chick, and frog muscle antigens for their
      cross-reactivity in zebrafish. Here, we present protocols for whole mount
      immunocytochemistry on both formaldehyde and Carnoy's fixed embryos as well as on
      sectioned zebrafish tissue. We include a table of antibodies useful for
      experiments on the molecular biology of myogenesis in zebrafish.

PMID- 22130837
TI  - Immunofluorescent localization of proteins in Caenorhabditis elegans muscle.
AB  - Caenorhabditis elegans is a premier model genetic system for discovering new
      information about the assembly and maintenance of striated muscle. The
      localization of a protein within a nematode muscle cell can reveal important
      clues to its function. In C. elegans, proteins can be localized by two different
      methods at the light microscopy level: GFP tagged proteins and indirect
      immunofluorescence. Although there are advantages and disadvantages of each
      method, antibodies can be used to localize proteins expressed at endogenous
      levels and without tags that might interfere with function. Immunolocalization
      requires efficient and effective methods of fixation. Here, we describe in detail
      two different methods for fixation of adult worms, the Nonet method and the
      Constant Spring method. We also discuss the advantages and the disadvantages of
      each, and how to choose between them. These methods are also useful for
      localizing proteins expressed in other cell types.

PMID- 22130838
TI  - Resistance loading and signaling assays for oxidative stress in rodent skeletal
      muscle.
AB  - Resistance loading provides an important tool for understanding skeletal muscle
      responses and adaptations to various perturbations. A model using anesthetized
      rodents provides the means to control the input parameters carefully, and to
      measure the output parameters of each muscle contraction. Unilateral models of
      anesthetized loading also provide the advantage of comparing an unloaded and
      loaded muscle from the same animal. Voluntary models for resistance loading
      arguably provide a more "physiological response" but it also introduces more
      variability in the input parameters, which can be affected by the stimulus used
      to motivate the animal to exercise. After either acute or chronic periods of
      muscle loading, the loaded muscles can be removed and various signaling proteins
      can be determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis
      (SDS-PAGE) or enzyme assays. Several assays are described, which provide an
      indication of downstream markers for oxidative stress.

PMID- 22130839
TI  - Analysis of skeletal muscle hypertrophy in models of increased loading.
AB  - Skeletal muscle is a highly adaptive tissue that modifies its size in response to
      a variety of external stimuli. In adult mammals, skeletal muscle hypertrophy
      occurs primarily as a response to increases in external loading. Here, we
      describe the methods that should be used for a comprehensive assessment of muscle
      hypertrophy in animal models. The methods include the measurement of muscle mass,
      fiber cross-sectional area, contractile function, and protein concentration.

PMID- 22130840
TI  - Protein overexpression in skeletal muscle using plasmid-based gene transfer to
      elucidate mechanisms controlling fiber size.
AB  - Plasmid DNA electrotransfer is a direct method of gene delivery to skeletal
      muscle commonly used to identify endogenous signaling pathways that mediate
      muscle remodeling or pathological states in adult rodents. When plasmids encoding
      a protein to be overexpressed are fused to a fluorescent protein or an epitope
      tag, plasmid electrotransfer permits visualization of the expressed protein in
      muscle fibers. Here, we demonstrate the use of electrotransfer of plasmids
      encoding mutant or wild type proteins to identify the role of the endogenous
      protein in regulating muscle fiber atrophy. The plasmids used encode a dominant
      negative form of the inhibitor of kappaB kinase beta (IKKbeta) fused to green
      fluorescent protein (GFP), a constitutively active form of IKKalpha fused to GFP,
      and a wild type IKKbeta fused to an HA tag. We show the effects of overexpression
      of these proteins on rat or mouse fiber size either with disuse atrophy or in
      normal weight bearing muscle. The effects of overexpressed proteins on myofiber
      size are assessed by comparing cross-sectional area of the transfected,
      fluorescent myofibers to the nontransfected, nonfluorescent myofibers. Using
      optimized intramuscular plasmid DNA injection and electroporation, we illustrate
      high transfection efficiency with no overt muscle damage using medium sized
      fusion proteins (105 kDa).

PMID- 22130841
TI  - In vivo measurement of muscle protein synthesis rate using the flooding dose
      technique.
AB  - Skeletal muscle mass is determined by the balance between rates of protein
      synthesis and degradation. Protein synthesis rates can be measured in vivo by
      administering an amino acid as a tracer that is labeled with an isotope
      (radioactive or stable) of C, H, or N. The rate at which the labeled amino acid
      is incorporated into muscle protein, as a function of the amount of labeled amino
      acid in the precursor pool at the site of translation, reflects the rate of
      protein synthesis. There are a number of approaches for performing this
      measurement depending on the question being addressed and the experimental system
      being studied. In this chapter, we describe the "flooding dose" approach using L
      [(3)H]-phenylalanine as the tracer and that is suitable for determining the rate
      of skeletal muscle protein synthesis (total and myofibrillar proteins) over an
      acute period (ideally less than 30 min) in any size animal; details for working
      with mice are presented. The method describes how to administer the tracer
      without anesthesia, the tissue collection, and the preparation of muscle and
      blood samples for analysis of the tracer and tracee amino acids in the precursor
      pool and in muscle proteins.

PMID- 22130843
TI  - Generation of lentiviral vectors for use in skeletal muscle research.
AB  - Gene therapy is a promising approach for the treatment of a variety of disorders
      including genetic diseases and cancer. Among the viral vectors used in gene
      therapy, the lentiviral vector, based on HIV-1, is the only integrative vector
      able to transduce nondividing cells. The first generation of lentiviral vector
      was -established in 1996. Since then, other generations of lentiviral vector
      packaging systems were developed to improve this first vector. In this chapter,
      we describe these different packaging systems, the generation of lentiviral
      vector from productive cells, the 293T cell line, and the transduction of
      myogenic cells with a lentiviral vector as well.

PMID- 22130842
TI  - Recombinant adeno-associated viral vector production and purification.
AB  - Gene delivery vectors based on recombinant adeno-associated virus (AAV) are
      powerful tools for studying myogenesis in normal and diseased conditions.
      Strategies have been developed to use AAV to increase, down-regulate, or modify
      expression of a particular muscle gene in a specific muscle, muscle group(s), or
      all muscles in the body. AAV-based muscle gene therapy has been shown to cure
      several inherited muscle diseases in animal models. Early clinical trials have
      also yielded promising results. In general, AAV vectors lead to robust, long-term
      in vivo transduction in rodents, dogs, and non-human primates. To meet specific
      research needs, investigators have developed numerous AAV variants by engineering
      viral capsid and/or genome. Here we outline a generic AAV production and
      purification protocol. Techniques described here are applicable to any AAV
      variant.

PMID- 22130844
TI  - Generating tamoxifen-inducible Cre alleles to investigate myogenesis in mice.
AB  - Gene inactivation has become the gold standard for determining gene function in
      the mouse. Many genes inactivated in the germ line cause early lethality that
      precludes phenotypic assessment at a later time point. Conditional gene
      inactivation using Cre recombinase expressed via a tissue specific
      promoter/enhancer allows phenotypic analyses of selected tissues, but lacks
      temporal control. Recent development of the tamoxifen-inducible Cre-ER (T2)
      offers both cell type-specific and temporal control of conditional gene
      inactivation. As an example, we describe the design and step-wise construction of
      a Cre-ER (T2) knock-in allele at the Pax7 locus using the recombineering method -
      Pax7 is selectively expressed in embryonic muscle progenitors and adult muscle
      stem cells. The resulting Pax7-Cre- ER (T2) (Pax7 (CE)) allele has been
      successfully applied to embryos and adults for tamoxifen-regulated myogenic
      lineage tracing and gene inactivation (Nature 460:627-631, 2009; Genesis 48:424
      436, 2010).

PMID- 22130845
TI  - Gene profiling studies in skeletal muscle by quantitative real-time polymerase
      chain reaction assay.
AB  - Gene profiling is an excellent tool to identify the genetic mechanisms, networks,
      and molecular pathways involved in skeletal muscle development and muscular
      disorders. Oligonucleotide or cDNA microarray can be the first step to identify
      the global gene expression in the study of interest. As microarray techniques
      provide a large set of differentially expressed genes in a given comparison, the
      expression profile can be narrowed down by taking various parameters into
      consideration such as fold values, p-values, and their relevance to the study.
      Every technique has its own limitations. Therefore, further validation of the
      results with a different technique is always necessary. Quantitative real-time
      reverse-transcriptase polymerase chain reaction (qRT-PCR) is the most common
      technique to validate microarray data and to study the relative expression of
      specific genes in any experimental set-up. Here, we describe, the qRT-PCR
      technique, in detail, for -successful gene expression studies in skeletal muscle
      cells and tissues.

PMID- 22130846
TI  - Analysis of lipid profiles in skeletal muscles.
AB  - The lipidome of skeletal muscles is a worthwhile target of research, as it
      affects a multitude of biological functions, and is, in turn, affected by factors
      such as diet, physical activity, and development. We present two methods for the
      analysis of the main lipid classes in skeletal muscles of humans and other
      animals, that is, triacylglycerols and phospholipids. The methods differ in that
      the former concerns total phospholipids, while the latter concerns individual
      phospholipids. In both methods, lipids are extracted from muscle after the
      addition of internal standards, and they are separated by one-dimensional (1D)
      thin-layer chromatography (TLC). This is sufficient for the separation of
      triacylglycerols and total phospholipids. In the first method, the two classes
      are subsequently subjected to methanolysis to produce methyl esters of fatty
      acids (and, to a lesser extent, dimethyl acetals of fatty aldehydes derived from
      plasmalogens), which are analyzed by gas chromatography (GC). Quantitation is
      achieved on the basis of the internal standards. In the second method, 1D TLC is
      used for the analysis of triacylglycerols only, whereas individual phospholipids
      are separated by two-dimensional TLC. This results in the isolation of
      phosphatidyl choline, lysophosphatidyl choline, phosphatidyl ethanolamine,
      phosphatidyl serine, phosphatidyl inositol, cardiolipin, and sphingomyelin.
      Methanolysis and subsequent analysis by GC results in the determination of the
      fatty acid and aldehyde profiles of the individual muscle phospholipids.

PMID- 22130847
TI  - Proteomic analysis of dystrophic muscle.
AB  - Mass spectrometry-based proteomics had a major impact on the global
      characterization of skeletal muscles and has decisively enhanced the field of
      neuromuscular pathology. Proteomic profiling of x-linked muscular dystrophy has
      identified a large number of new signature molecules involved in fiber
      degeneration. Here, we describe the difference in-gel electrophoretic analysis of
      the dystrophic diaphragm muscle from the MDX mouse model of Duchenne muscular
      dystrophy. This chapter summarizes the various experimental steps involved in
      muscle proteomics, such as sample preparation, fluorescence labeling, isoelectric
      focusing, second-dimension slab gel electrophoresis, image analysis, in-gel
      digestion and electrospray ionization mass spectrometry.

PMID- 22130848
TI  - Detection of calcium release via ryanodine receptors.
AB  - The ryanodine receptor ion channels (RyRs) release Ca(2+) from the
      endo/sarcoplasmic reticulum in a variety of nonvertebrate and vertebrate species
      including flies, crustaceans, birds, fish, and amphibians. They are most abundant
      in skeletal and cardiac muscle, where in response to an action potential, the
      release of Ca(2+) ions from the sarcoplasmic reticulum through the RyRs into the
      cytoplasm leads to muscle contraction (i.e., excitation-contraction coupling).
      Here, we describe how to determine their cellular location using isoform-specific
      antibodies, their protein levels using an in vitro ((3)H)ryanodine-binding assay,
      and their cellular release of Ca(2+) using RyR-specific channel agonists and
      inhibitors.

PMID- 22130849
TI  - Measurement of calcium release due to inositol trisphosphate receptors in
      skeletal muscle.
AB  - Calcium transients elicited by IP(3) receptors upon electrical stimulation of
      skeletal muscle cells (slow calcium signals) are often hard to visualize due to
      their relatively small amplitude compared to the large transient originated from
      ryanodine receptors associated to excitation-contraction coupling. The study of
      slow calcium transients, however, is relevant due to their function in regulation
      of muscle gene expression and in the process of excitation-transcription
      coupling. Discussed here are the procedures used to record slow calcium signals
      from both cultured mouse myotubes and from cultured adult skeletal muscle fibers.

PMID- 22130850
TI  - Detection of calcium sparks in intact and permeabilized skeletal muscle fibers.
AB  - Ca(2+) sparks are the elementary units of Ca(2+) signaling in striated muscle
      fibers that appear as highly localized Ca(2+) release events through ryanodine
      receptor (RyR) Ca(2+) release channels in the sarcoplasmic reticulum (SR). While
      these events are commonly observed in resting cardiac myocytes, they are rarely
      seen in resting skeletal muscle fibers. Since Ca(2+) spark analysis can provide
      extensive data on the Ca(2+) handling characteritsics of normal and diseased
      striated muscle, there has been interest in developing methods for observing
      Ca(2+) sparks in skeletal muscle. Previously, we discovered that stress generated
      by osmotic pressure changes induces a robust Ca(2+) spark response confined in
      close spatial proximity to the sarcolemmal membrane in wild-type intact mammalian
      muscles. Our studies showed these peripheral Ca(2+) sparks (PCS) were altered in
      dystrophic or aged skeletal muscles. Other methods to induce Ca(2+) sparks
      include permeabilization of the sarcolemmal membrane with detergents, such as
      saponin. In this chapter, we will discuss the methods for isolation of muscle
      fibers, the techniques for inducing Ca(2+) sparks in these isolated fibers, and
      provide guidance on the analysis of data from these experiments.

PMID- 22130851
TI  - Analysis of calcium transients in cardiac myocytes and assessment of the
      sarcoplasmic reticulum Ca2+-ATPase contribution.
AB  - Ca(2+) signaling plays an essential role in several functions of cardiac
      myocytes. Transient rises and reductions of cytosolic Ca(2+), permitted by the
      sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) and other proteins, control each
      cycle of contraction and relaxation. Here we provide a practical method for
      isolation of neonatal rat cardiac myocytes and measurement of Ca(2+) transients
      in cultured cardiac myocytes, yielding information on kinetic resolution of the
      transients, variations of cytosolic Ca(2+) concentrations, and adequacy of
      intracellular Ca(2+) stores. We also provide examples of experimental
      perturbations that can be used to assess the contribution of SERCA2 to Ca(2+)
      signaling.

PMID- 22130852
TI  - Analysis of muscle gene transcription in cultured skeletal muscle cells.
AB  - The mechanisms by which muscle gene expression is initiated and maintained are
      not fully understood. Muscle genes are regulated by combinatorial interactions
      between numerous transcription factors bound to enhancers and promoters, and
      their associated protein complexes. Among the most important are the MyoD and
      MEF2 transcription factor families, but dozens of other factors play important
      regulatory roles, and many additional transcription factors are certain to be
      involved. Expression of muscle-specific genes varies among different anatomical
      muscles and in fast- vs. slow-twitch fiber types, suggesting different mechanisms
      of regulation in response to diverse physiological cues. Thus, identifying novel
      transcriptional regulators and interactions is key to understanding how different
      cells establish the muscle phenotype; it is also critical for developing methods
      to combat diseases such as muscular dystrophy. Using Muscle creatine kinase as a
      model, we outline the key steps involved in identifying muscle gene control
      elements, their binding factors, and mechanisms of transcriptional activation and
      repression. The basic principles described here can also be applied to the
      transcriptional analysis of other cell-type specific genes.

PMID- 22130853
TI  - Analysis of fiber-type differences in reporter gene expression of beta-gal
      transgenic muscle.
AB  - beta-galactosidase (beta-gal) is among the most frequently used markers for
      studying a wide variety of biological mechanisms, e.g., gene expression, cell
      migration, stem cell conversion to different cell types, and gene silencing. Many
      of these studies require the histochemical detection of relative beta-gal levels
      in tissue cross-sections mounted onto glass slides and visualized by microscopy.
      This is particularly useful for the analysis of promoter activity in skeletal
      muscle tissue since the beta-gal levels can vary dramatically between different
      anatomical muscles and myofiber types. The differences in promoter activity can
      be due to a myofiber's developmental history, innervation, response to normal or
      experimental physiological signals, and its disease state. It is thus important
      to identify the individual fiber types within muscle cross-sections and to
      correlate these with transgene expression signals. Here, we provide a detailed
      description of how to process and analyze muscle tissues to determine the fiber
      type composition and beta-gal transgene expression within cryosections.

PMID- 22130854
TI  - Determination of gene promoter activity in skeletal muscles in vivo.
AB  - The use of nonviral (plasmid DNA) gene delivery into skeletal muscle has
      increased significantly in recent years. The procedure is used to overexpress
      wild-type proteins, express mutant proteins, or knock down endogenous proteins.
      These manipulations can identify the role of a specific protein in muscle cell
      biology and physiology. The same procedure of plasmid DNA gene delivery can be
      used to introduce a gene promoter reporter construct. Such constructs contain a
      defined sequence of a gene promoter that regulates the expression of a
      "reporter." This reporter is easily measured and reflects the in vivo
      transcriptional activity of the gene promoter sequence under study. The gene
      promoter can be mutated at known transcription factor-binding sites, truncated to
      identify specific regions of the gene promoter that are required for
      transcription, or introduced into skeletal muscle with an expression plasmid for
      a protein believed to regulate the gene's transcription. Therefore, the use of
      such gene promoter reporters allows for an in-depth physiological assessment of
      the gene's transcriptional regulation.

PMID- 22130855
TI  - Determination of miRNA targets in skeletal muscle cells.
AB  - MicroRNAs (miRNAs) are a class of small ~22 nucleotide noncoding RNAs which
      regulate gene expression at the posttranscriptional level by either destabilizing
      and consequently degrading their targeted mRNAs or by repressing their
      translation. Emerging evidence has demonstrated that miRNAs are essential for
      normal mammalian development, homeostasis, and many other functions. In addition,
      deleterious changes in miRNA expression were associated with human diseases.
      Several muscle-specific miRNAs, including miR-1, miR-133, miR-206, and miR-208,
      have been shown to be important for normal myoblast differentiation,
      proliferation, and muscle remodeling in response to stress. They have also been
      implicated in various cardiac and skeletal muscular diseases. miRNA-based gene
      therapies hold great potential for the treatment of cardiac and skeletal muscle
      diseases. Herein, we describe methods commonly applied to study the biological
      role of miRNAs, as well as techniques utilized to manipulate miRNA expression and
      to investigate their target regulation.

PMID- 22130856
TI  - shRNA-mediated gene knockdown in skeletal muscle.
AB  - RNA interference appears as a promising tool for therapeutic gene silencing to
      block protein expression. A long-lived silencing is obtained through the in situ
      expression of shRNA. A safe approach is to use a physical method such as in vivo
      electropulsation with plate electrodes. This is presently validated in muscles by
      the in vivo coelectrotransfer of plasmids specifically coding for expression and
      silencing of a fluorescent protein. No long-lived tissue damage is observed by
      the proper choice of the electric pulsing parameters and the amount of injected
      plasmids. Using a noninvasive fluorescence imaging assay, electrodelivery in
      mouse muscles is observed to induce complete silencing over more than 2 months in
      a specific way. The proper choices of the plasmids (sequence, promoter, and
      relative amounts) appear as key parameters in the successful long-term silencing.

PMID- 22130857
TI  - Detection of NF-kappaB activity in skeletal muscle cells by electrophoretic
      mobility shift analysis.
AB  - An electrophoretic mobility shift assay (EMSA) is a common and invaluable
      technique which can be utilized to study the affinity of proteins to a specific
      DNA or RNA sequence. These assays are performed in vitro with protein extracts
      isolated from either cultured cells or isolated tissues. Here, we describe the
      methodology used to isolate the cytoplasmic and nuclear protein extracts from
      both cultured cells and tissues and utilize the nuclear protein fraction to
      assess NF-kappaB DNA-binding activity by EMSA analysis.

PMID- 22130858
TI  - Isolation of nuclei from skeletal muscle satellite cells and myofibers for use in
      chromatin immunoprecipitation assays.
AB  - Studies investigating mechanisms controlling gene regulation frequently examine
      specific DNA sequences using chromatin immunoprecipitation (ChIP) assays to
      determine whether specific regulatory factors or modified histones are present.
      While use of primary cells or cell line models for differentiating or
      differentiated tissue is widespread, the ability to assess factor binding and
      histone modification in tissue defines the events that occur in vivo and provides
      corroboration for studies in cultured cells. Many tissues can be analyzed with
      minimal modification to existing ChIP protocols that are designed for cultured
      cells; however, some tissues, such as skeletal muscle, are problematic in that
      accessibility of the cross-linking agent is limited. We describe a method to
      isolate skeletal muscle tissue nuclei suitable for use in ChIP protocols.
      Furthermore, we utilize a simple fractionation of digested skeletal muscle tissue
      that can separate mature myofibers from satellite cells, which are responsible
      for postnatal skeletal muscle regeneration, thereby allowing simultaneous
      preparation of nuclei from both cell types.

PMID- 22130859
TI  - An improved restriction enzyme accessibility assay for analyzing changes in
      chromatin structure in samples of limited cell number.
AB  - Studies investigating mechanisms that control gene regulation frequently examine
      the accessibility of specific DNA sequences to nuclease cleavage. In general,
      sequences that are sensitive to nuclease cleavage are considered to be in an
      "open" chromatin conformation that is associated with regulatory factor binding,
      while sequences resistant to nuclease cleavage are considered to be in a "closed"
      conformation commonly associated with chromatin that is neither poised for
      transcription nor being actively transcribed. Changes in nuclease accessibility
      at specific genomic sequences reflect changes in the local chromatin structure
      that can occur as a result of signaling cues in the extracellular environment.
      These changes in chromatin structure usually precede or are coincident with
      changes in gene expression patterns and are therefore a useful marker of
      regulatory events controlling transcription. We describe a method to perform
      restriction enzyme accessibility assays (REAA) that utilizes ligation-mediated
      polymerase chain reaction (LM-PCR) technology and that permits assessment of
      samples from any source containing as few as 1,000 cells. Use of this modified
      REAA protocol will enhance analysis of chromatin structural changes at specific
      DNA sequences of interest by making it possible to analyze samples where
      unrestricted amounts of sample are not readily available.

PMID- 22130860
TI  - ChIP-enriched in silico targets (ChEST), a ChIP-on-chip approach applied to
      analyzing skeletal muscle genes.
AB  - Mapping the cis-regulatory modules (CRMs) to which bind myogenic transcription
      factors is an -obligatory step towards understanding gene regulatory networks
      governing muscle development and function. This can be achieved in silico or by
      chromatin immunoprecipitation (ChIP) approaches. We have developed a ChIP
      enriched in silico targets (ChEST) strategy designed for mapping the CRMs by
      combining in silico and ChIP methods. ChEST involves a software-assisted
      prediction of transcription factor (TF) - specific CRMs, which are spotted to
      produce a computed genomic CRM microarray. In parallel, the in vivo pool of
      targets of a given TF is isolated by ChIP and used as a probe for hybridization
      with the array generated. Here we describe ChEST strategy applied to identify
      direct targets of Myogenic Enhancer Factor, Dmef2 in Drosophila embryos.

PMID- 22130862
TI  - Retraction. Chewing ability in an adult Chinese population.

PMID- 22130861
TI  - An ethylene response factor OsWR1 responsive to drought stress transcriptionally
      activates wax synthesis related genes and increases wax production in rice.
AB  - Increasing evidence has revealed the major enzymes-involved in Arabidopsis and
      maize wax/cutin synthesis; however, there is limited information about the genes
      associated with wax/cutin synthesis in rice. Here we report the characterization
      of an ethylene response factor gene in rice. This rice wax synthesis regulatory
      gene 1 (OsWR1) is a homolog of Arabidopsis wax/cutin synthesis regulatory gene
      WIN1/SHN1. Transcript analysis showed that OsWR1 is induced by drought, abscisic
      acid and salt, and is predominantly expressed in leaves. Functional analyses
      indicated that overexpressing OsWR1 (Ox-WR1) improved while RNA interference
      OsWR1 rice (RI-WR1) decreased drought tolerance, consistent with water loss and
      cuticular permeability, suggesting that OsWR1-triggered drought response might be
      associated with cuticular characteristics. In addition, OsWR1 activated the
      expression of the genes-related to oxidative stress response and membrane
      stability. Gas chromatograph-mass spectrometry analysis further showed that OsWR1
      modulated the wax synthesis through alteration of long chain fatty acids and
      alkanes, evidencing the regulation of OsWR1 in wax synthesis. Detection with real
      time PCR amplification indicated that Ox-WR1 enhanced while RI-WR1 decreased the
      expression of wax/cutin synthesis related genes. Furthermore, OsWR1 physically
      interacted with the DRE and GCC box in the promoters of wax related genes OsLACS2
      and OsFAE1'-L, indicating that OsWR1 at least directly modulates the expression
      of these genes. Thus our results indicate that OsWR1 is a positive regulator of
      wax synthesis related genes in rice, and this regulation, distinct from its
      homology regulator of WIN1/SHN1 in cutin synthesis, subsequently contributes to
      reduced water loss and enhanced drought tolerance.

PMID- 22130863
TI  - Assessment of lipopolysaccharide microleakage at conical implant-abutment
      connections.
AB  - OBJECTIVE: The aim of this in vitro study was to assess lipopolysaccharide
      microleakage at conical implant-abutment connections of two-piece dental implants
      in terms of the expression levels of genes involved in lipopolysaccharide
      mediated proinflammatory cytokine production. MATERIALS AND METHODS: Two implant
      systems with conical implant-abutment connections were inoculated with
      lipopolysaccharide and submerged in human whole blood. Positive-control blood
      samples (without implants) were stimulated with 4 MUg/ml, 2 MUg/ml, 200 ng/ml,
      and 20 ng/ml lipopolysaccharide. Sampling was performed after 1, 8, and 24 h of
      incubation. Changes of gene expression levels of Toll-like receptor 9, tumor
      necrosis factor-alpha, nuclear factor kappa light chain enhancer of activated B
      cells, interleukin-1beta, and interferon-gamma were assessed by real-time
      quantitative PCR. In addition, protein expression levels of interleukin-6, tumor
      necrosis factor-alpha, interleukin-1beta, and interferon-gamma were determined by
      immunoassay. RESULTS: Changes in cytokine expression at the genomic and proteomic
      levels indicated lipopolysaccharide leakage at the interfaces of both tested
      implant systems, although some implants showed no sign of microleakage. Any
      tested concentration of lipopolysaccharide stimulated similar gene expression.
      CONCLUSIONS: Conical implant-abutment connections of two-piece dental implants do
      not prevent microleakage on a molecular level. Changes in lipopolysaccharide
      induced proinflammatory cytokine gene expression facilitate the detection of
      lipopolysaccharide microleakage at implant-abutment interfaces. CLINICAL
      RELEVANCE: Small amounts of lipopolysaccharide released from intra-implant
      cavities can stimulate a detectable immunological response in human whole blood
      and may induce alveolar bone resorption via the osteoclast-activating pathway.

PMID- 22130864
TI  - Luck.

PMID- 22130867
TI  - Vitamin D intake, vitamin D receptor polymorphisms, and breast cancer risk among
      women living in the southwestern U.S.
AB  - No studies of dietary vitamin D intake and vitamin D receptor (VDR) have been
      conducted comparing breast risk among Hispanic women and non-Hispanic white (NHW)
      women. We investigated the association between vitamin D intake and breast cancer
      in a population-based case-control study of 1,527 NHW and 791 Hispanic breast
      cancer cases diagnosed in 1999-2004 in Arizona, New Mexico, Utah, and Colorado,
      and 1,599 NHW and 922 Hispanic age-matched controls. Vitamin D intake was
      assessed using food frequency questionnaires, and associations with breast cancer
      were adjusted for age, ethnicity, state, education, body mass index, smoking, age
      at menarche, age at first birth, parity, hormone exposure, height, and physical
      activity using logistic regression. BsmI, Poly A and FokI vitamin D receptor
      (VDR) genotypes were also measured. Dietary vitamin D intake was positively
      associated with breast cancer (highest vs. lowest quartile (Q (4) vs. Q (1)):
      odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.15-1.60; P (trend) =
      0.003), whereas vitamin D supplement use was inversely associated with breast
      cancer (10+ MUg/day vs. none: OR = 0.79, 95% CI = 0.65-0.96, P (trend) = 0.01).
      Similar patterns in risk were observed by ethnicity and menopausal status.
      Positive associations with dietary vitamin D intake and inverse associations with
      supplement use were observed for ER+/PR+ and ER-/PR- breast cancers, but not for
      ER+/PR- disease. BsmI genotype significantly modified the association between
      dietary vitamin D and breast cancer overall. Future research is needed to better
      understand potential differences in breast cancer risk by vitamin D source and
      hormone receptor status.

PMID- 22130868
TI  - Syntheses of furo[3,4-c]coumarins and related furyl coumarin derivatives via
      intramolecular Wittig reactions.
AB  - A new and general strategy for highly functional furo[3,4-c]coumarins and related
      furyl coumarin derivatives has been developed, which is based on an
      extraordinarily facile intramolecular Wittig reaction, starting from alpha,beta
      unsaturated ketones, tributylphosphine, and acyl chlorides. The phosphorus ylides
      were proposed to be the key intermediates for constructing the crucial furan
      ring, leading to a wide variety of substituted furyl coumarins in one step.

PMID- 22130869
TI  - Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine
      on psychomotor function and histamine-induced wheal- and flare-responses: a
      randomized double-blind, placebo-controlled study in healthy volunteers.
AB  - Since most first-generation antihistamines have undesirable sedative effects on
      the central nervous systems (CNS), newer (second-generation) antihistamines have
      been developed to improve patients' quality of life. However, there are few
      reports that directly compare the antihistaminic efficacy and impairment of
      psychomotor functions. We designed a double-blind, placebo controlled, crossover
      study to concurrently compare the clinical effectiveness of promethazine, a first
      generation antihistamine, and fexofenadine and olopatadine, second-generation
      antihistamines, by measuring their potency as peripheral inhibitors of histamine
      induced wheal and flare. Further, we investigated their sedative effects on the
      CNS using a battery of psychomotor tests. When single therapeutic doses of
      fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a
      double-blind manner to 24 healthy volunteers, all antihistamines produced a
      significant reduction in the wheal and flare responses induced by histamine. In
      the comparison among antihistamines, olopatadine showed a rapid inhibitory effect
      compared with fexofenadine and promethazine, and had a potent effect compared
      with promethazine. In a battery of psychomotor assessments using critical flicker
      fusion, choice reaction time, compensatory tracking, rapid visual information
      processing and a line analogue rating scale as a subjective assessment of
      sedation, promethazine significantly impaired psychomotor function. Fexofenadine
      and olopatadine had no significant effect in any of the psychomotor tests.
      Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as
      measured by wrist actigraphy. These results suggest that olopatadine at a
      therapeutic dose has greater antihistaminergic activity than promethazine, and
      olopatadine and fexofenadine did not cause cognitive or psychomotor impairment.

PMID- 22130870
TI  - A primer on the current state of microarray technologies.
AB  - DNA microarray technology has been used for genome-wide gene expression studies
      that incorporate molecular genetics and computer science analyses on massive
      levels. The availability of microarrays permit the simultaneous analysis of tens
      of thousands of genes for the purposes of gene discovery, disease diagnosis,
      improved drug development, and therapeutics tailored to specific disease
      processes. In this chapter, we provide an overview on the current state of common
      microarray technologies and platforms. Since many genes contribute to normal
      functioning, research efforts are moving from the search for a disease-specific
      gene to the understanding of the biochemical and molecular functioning of a
      variety of genes whose disrupted interaction in complicated networks can lead to
      a disease state. The field of microarrays has evolved over the past decade and is
      now standardized with a high level of quality control, while providing a
      relatively inexpensive and reliable alternative to studying various aspects of
      gene expression.

PMID- 22130871
TI  - The KEGG databases and tools facilitating omics analysis: latest developments
      involving human diseases and pharmaceuticals.
AB  - In this chapter, we demonstrate the usability of the KEGG (Kyoto encyclopedia of
      genes and genomes) databases and tools, especially focusing on the visualization
      of the omics data. The desktop application KegArray and many Web-based tools are
      tightly integrated with the KEGG knowledgebase, which helps visualize and
      interpret large amount of data derived from high-throughput measurement
      techniques including microarray, metagenome, and metabolome analyses. Recently
      developed resources for human disease, drug, and plant research are also
      mentioned.

PMID- 22130872
TI  - Strategies to explore functional genomics data sets in NCBI's GEO database.
AB  - The Gene Expression Omnibus (GEO) database is a major repository that stores high
      throughput functional genomics data sets that are generated using both microarray
      based and sequence-based technologies. Data sets are submitted to GEO primarily
      by researchers who are publishing their results in journals that require original
      data to be made freely available for review and analysis. In addition to serving
      as a public archive for these data, GEO has a suite of tools that allow users to
      identify, analyze, and visualize data relevant to their specific interests. These
      tools include sample comparison applications, gene expression profile charts,
      data set clusters, genome browser tracks, and a powerful search engine that
      enables users to construct complex queries.

PMID- 22130873
TI  - Analyzing cancer samples with SNP arrays.
AB  - Single nucleotide polymorphism (SNP) arrays are powerful tools to delineate
      genomic aberrations in cancer genomes. However, the analysis of these SNP array
      data of cancer samples is complicated by three phenomena: (a) aneuploidy: due to
      massive aberrations, the total DNA content of a cancer cell can differ
      significantly from its normal two copies; (b) nonaberrant cell admixture: samples
      from solid tumors do not exclusively contain aberrant tumor cells, but always
      contain some portion of nonaberrant cells; (c) intratumor heterogeneity:
      different cells in the tumor sample may have different aberrations. We describe
      here how these phenomena impact the SNP array profile, and how these can be
      accounted for in the analysis. In an extended practical example, we apply our
      recently developed and further improved ASCAT (allele-specific copy number
      analysis of tumors) suite of tools to analyze SNP array data using data from a
      series of breast carcinomas as an example. We first describe the structure of the
      data, how it can be plotted and interpreted, and how it can be segmented. The
      core ASCAT algorithm next determines the fraction of nonaberrant cells and the
      tumor ploidy (the average number of DNA copies), and calculates an ASCAT profile.
      We describe how these ASCAT profiles visualize both copy number aberrations as
      well as copy-number-neutral events. Finally, we touch upon regions showing
      intratumor heterogeneity, and how they can be detected in ASCAT profiles. All
      source code and data described here can be found at our ASCAT Web site (
      http://www.ifi.uio.no/forskning/grupper/bioinf/Projects/ASCAT/).

PMID- 22130874
TI  - Classification approaches for microarray gene expression data analysis.
AB  - Classification approaches have been developed, adopted, and applied to
      distinguish disease classes at the molecular level using microarray data.
      Recently, a novel class of hierarchical probabilistic models based on a kernel
      imbedding technique has become one of the best classification tools for
      microarray data analysis. These models were first developed as kernel-imbedded
      Gaussian processes (KIGPs) for binary class classification problems using
      microarray gene expression data, then they were further improved for multiclass
      classification problems under a unifying Bayesian framework. Specifically, an
      adaptive algorithm with a cascading structure was designed to find appropriate
      featuring kernels, to discover potentially significant genes, and to make optimal
      disease (e.g., tumor/cancer) class predictions with associated Bayesian posterior
      probabilities. Simulation studies and applications to publish real data showed
      that KIGPs performed very close to the Bayesian bound and consistently
      outperformed or performed among the best of a lot of state-of-the-art methods.
      The most unique advantage of the KIGP approach is its ability to explore both the
      linear and the nonlinear underlying relationships between the target features of
      a given disease classification problem and the involved explanatory gene
      expression data. This line of research has shed light on the broader usability of
      the KIGP approach for the analysis of other high-throughput omics data and omics
      data collected in time series fashion, especially when linear model based methods
      fail to work.

PMID- 22130875
TI  - Biclustering of time series microarray data.
AB  - Clustering is a popular data exploration technique widely used in microarray data
      analysis. In this chapter, we review ideas and algorithms of bicluster and its
      applications in time series microarray analysis. We introduce first the concept
      and importance of biclustering and its different variations. We then focus our
      discussion on the popular iterative signature algorithm (ISA) for searching
      biclusters in microarray dataset. Next, we discuss in detail the enrichment
      constraint time-dependent ISA (ECTDISA) for identifying biologically meaningful
      temporal transcription modules from time series microarray dataset. In the end,
      we provide an example of ECTDISA application to time series microarray data of
      Kaposi's Sarcoma-associated Herpesvirus (KSHV) infection.

PMID- 22130876
TI  - Using the bioconductor GeneAnswers package to interpret gene lists.
AB  - Use of microarray data to generate expression profiles of genes associated with
      disease can aid in identification of markers of disease and potential therapeutic
      targets. Pathway analysis methods further extend expression profiling by creating
      inferred networks that provide an interpretable structure of the gene list and
      visualize gene interactions. This chapter describes GeneAnswers, a novel gene
      concept network analysis tool available as an open source Bioconductor package.
      GeneAnswers creates a gene-concept network and also can be used to build protein
      protein interaction networks. The package includes an example multiple myeloma
      cell line dataset and tutorial. Several network analysis methods are included in
      GeneAnswers, and the tutorial highlights the conditions under which each type of
      analysis is most beneficial and provides sample code.

PMID- 22130877
TI  - Analysis of isoform expression from splicing array using multiple comparisons.
AB  - There is a high prevalence of alternatively spliced genes (isoforms) in the human
      genome. Studies toward understanding aberrantly spliced genes and their
      association with diseases have lead researchers to profile the expression of
      alternatively spliced products. High-throughput profiling of isoforms has been
      done using microarray technology. Expression of isoforms reflects regulation both
      at transcriptional and posttranscriptional levels. This chapter details the
      methods to perform exhaustive comparison of isoforms using the R statistical
      framework.

PMID- 22130878
TI  - Functional comparison of microarray data across multiple platforms using the
      method of percentage of overlapping functions.
AB  - Functional comparison across microarray platforms is used to assess the
      comparability or similarity of the biological relevance associated with the gene
      expression data generated by multiple microarray platforms. Comparisons at the
      functional level are very important considering that the ultimate purpose of
      microarray technology is to determine the biological meaning behind the gene
      expression changes under a specific condition, not just to generate a list of
      genes. Herein, we present a method named percentage of overlapping functions
      (POF) and illustrate how it is used to perform the functional comparison of
      microarray data generated across multiple platforms. This method facilitates the
      determination of functional differences or similarities in microarray data
      generated from multiple array platforms across all the functions that are
      presented on these platforms. This method can also be used to compare the
      functional differences or similarities between experiments, projects, or
      laboratories.

PMID- 22130879
TI  - Performance comparison of multiple microarray platforms for gene expression
      profiling.
AB  - With genome-wide gene expression microarrays being increasingly applied in
      various areas of biomedical research, the diversity of platforms and analytical
      methods has made comparison of data from multiple platforms very challenging. In
      this chapter, we describe a generalized framework for systematic comparisons
      across gene expression profiling platforms, which could accommodate both the
      available commercial arrays and "in-house" platforms, with both one-dye and two
      dye platforms. It includes experimental design, data preprocessing protocols,
      cross-platform gene matching approaches, measures of data consistency
      comparisons, and considerations in biological validation. In the design of this
      framework, we considered the variety of platforms available, the need for uniform
      quality control procedures, real-world practical limitations, statistical
      validity, and the need for flexibility and extensibility of the framework. Using
      this framework, we studied ten diverse microarray platforms, and we conclude that
      using probe sequences matched at the exon level is important to improve cross
      platform data consistency compared to annotation-based matches. Generally,
      consistency was good for highly expressed genes, and variable for genes with
      lower expression values, as confirmed by QRT-PCR. After stringent preprocessing,
      commercial arrays were more consistent than "in-house" arrays, and by most
      measures, one-dye platforms were more consistent than two-dye platforms.

PMID- 22130880
TI  - Integrative approaches for microarray data analysis.
AB  - Microarrays were one of the first technologies of the genomic revolution to gain
      widespread adoption, rapidly expanding from a cottage industry to the source of
      thousands of experimental results. They were one of the first assays for which
      data repositories and metadata were standardized and researchers were required by
      many journals to make published data publicly available. Microarrays provide high
      throughput insights into the biological functions of genes and gene products;
      however, they also present a "curse of dimensionality," whereby the availability
      of many gene expression measurements in few samples make it challenging to
      distinguish noise from true biological signal. All of these factors argue for
      integrative approaches to microarray data analysis, which combine data from
      multiple experiments to increase sample size, avoid laboratory-specific bias, and
      enable new biological insights not possible from a single experiment. Here, we
      discuss several approaches to integrative microarray analysis for a diverse range
      of applications, including biomarker discovery, gene function and interaction
      prediction, and regulatory network inference. We also show how, by integrating
      large microarray compendia with diverse genomic data types, more nuanced
      biological hypotheses can be explored computationally. This chapter provides
      overviews and brief descriptions of each of these approaches to microarray
      integration.

PMID- 22130881
TI  - Modeling gene regulation networks using ordinary differential equations.
AB  - Gene regulation networks are composed of transcription factors, their
      interactions, and targets. It is of great interest to reconstruct and study these
      regulatory networks from genomics data. Ordinary differential equations (ODEs)
      are popular tools to model the dynamic system of gene regulation networks.
      Although the form of ODEs is often provided based on expert knowledge, the values
      for ODE parameters are seldom known. It is a challenging problem to infer ODE
      parameters from gene expression data, because the ODEs do not have analytic
      solutions and the time-course gene expression data are usually sparse and
      associated with large noise. In this chapter, we review how the generalized
      profiling method can be applied to obtain estimates for ODE parameters from the
      time-course gene expression data. We also summarize the consistency and
      asymptotic normality results for the generalized profiling estimates.

PMID- 22130882
TI  - Nonhomogeneous dynamic Bayesian networks in systems biology.
AB  - Dynamic Bayesian networks (DBNs) have received increasing attention from the
      computational biology community as models of gene regulatory networks. However,
      conventional DBNs are based on the homogeneous Markov assumption and cannot deal
      with inhomogeneity and nonstationarity in temporal processes. The present chapter
      provides a detailed discussion of how the homogeneity assumption can be relaxed.
      The improved method is evaluated on simulated data, where the network structure
      is allowed to change with time, and on gene expression time series during
      morphogenesis in Drosophila melanogaster.

PMID- 22130883
TI  - Inference of regulatory networks from microarray data with R and the bioconductor
      package qpgraph.
AB  - Regulatory networks inferred from microarray data sets provide an estimated
      blueprint of the functional interactions taking place under the assayed
      experimental conditions. In each of these experiments, the gene expression
      pathway exerts a finely tuned control simultaneously over all genes relevant to
      the cellular state. This renders most pairs of those genes significantly
      correlated, and therefore, the challenge faced by every method that aims at
      inferring a molecular regulatory network from microarray data, lies in
      distinguishing direct from indirect interactions. A straightforward solution to
      this problem would be to move directly from bivariate to multivariate statistical
      approaches. However, the daunting dimension of typical microarray data sets, with
      a number of genes p several orders of magnitude larger than the number of samples
      n, precludes the application of standard multivariate techniques and confronts
      the biologist with sophisticated procedures that address this situation. We have
      introduced a new way to approach this problem in an intuitive manner, based on
      limited-order partial correlations, and in this chapter we illustrate this method
      through the R package qpgraph, which forms part of the Bioconductor project and
      is available at its Web site.

PMID- 22130884
TI  - Effective non-linear methods for inferring genetic regulation from time-series
      microarray gene expression data.
AB  - Owing to the quick development of high-throughput techniques and the generation
      of various "omics" datasets, it creates a prospect of performing the study of
      genome-wide genetic regulatory networks. Here, we present a sophisticated
      modelling framework together with the corresponding inference methods for
      accurately estimating genetic regulation from time-series microarray data. By
      applying our non-linear model on human p53 microarray expression data, we
      successfully estimated the activities of transcription factor (TF) p53 as well as
      identified the activation/inhibition status of p53 to its target genes. The
      predicted top 317 putative p53 target genes were supported by DNA sequence
      analysis. Our quantitative model can not only be used to infer the regulatory
      relationship between TF and its downstream genes but also be applied to estimate
      the protein activities of TF from the expression levels of its target genes.

PMID- 22130885
TI  - An overview of the analysis of next generation sequencing data.
AB  - Next generation sequencing is a common and versatile tool for biological and
      medical research. We describe the basic steps for analyzing next generation
      sequencing data, including quality checking and mapping to a reference genome. We
      also explain the further data analysis for three common applications of next
      generation sequencing: variant detection, RNA-seq, and ChIP-seq.

PMID- 22130886
TI  - How to analyze gene expression using RNA-sequencing data.
AB  - RNA-Seq is arising as a powerful method for transcriptome analyses that will
      eventually make microarrays obsolete for gene expression analyses. Improvements
      in high-throughput sequencing and efficient sample barcoding are now enabling
      tens of samples to be run in a cost-effective manner, competing with microarrays
      in price, excelling in performance. Still, most studies use microarrays, partly
      due to the ease of data analyses using programs and modules that quickly turn raw
      microarray data into spreadsheets of gene expression values and significant
      differentially expressed genes. Instead RNA-Seq data analyses are still in its
      infancy and the researchers are facing new challenges and have to combine
      different tools to carry out an analysis. In this chapter, we provide a tutorial
      on RNA-Seq data analysis to enable researchers to quantify gene expression,
      identify splice junctions, and find novel transcripts using publicly available
      software. We focus on the analyses performed in organisms where a reference
      genome is available and discuss issues with current methodology that have to be
      solved before RNA-Seq data can utilize its full potential.

PMID- 22130887
TI  - Analyzing ChIP-seq data: preprocessing, normalization, differential
      identification, and binding pattern characterization.
AB  - Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a high
      throughput antibody-based method to study genome-wide protein-DNA binding
      interactions. ChIP-seq technology allows scientist to obtain more accurate data
      providing genome-wide coverage with less starting material and in shorter time
      compared to older ChIP-chip experiments. Herein we describe a step-by-step
      guideline in analyzing ChIP-seq data including data preprocessing, nonlinear
      normalization to enable comparison between different samples and experiments,
      statistical-based method to identify differential binding sites using mixture
      modeling and local false discovery rates (fdrs), and binding pattern
      characterization. In addition, we provide a sample analysis of ChIP-seq data
      using the steps provided in the guideline.

PMID- 22130888
TI  - Identifying differential histone modification sites from ChIP-seq data.
AB  - Epigenetic modifications are critical to gene regulations and genome functions.
      Among different epigenetic modifications, it is of great interest to study the
      differential histone modification sites (DHMSs), which contribute to the
      epigenetic dynamics and the gene regulations among various cell-types or
      environmental responses. ChIP-seq is a robust and comprehensive approach to
      capture the histone modifications at the whole genome scale. By comparing two
      histone modification ChIP-seq libraries, the DHMSs are potentially identifiable.
      With this aim, we proposed an approach called ChIPDiff for the genome-wide
      comparison of histone modification sites identified by ChIP-seq (Xu, Wei, Lin et
      al., Bioinformatics 24:2344-2349, 2008). The approach employs a hidden Markov
      model (HMM) to infer the states of histone modification changes at each genomic
      location. We evaluated the performance of ChIPDiff by comparing the H3K27me3
      modification sites between mouse embryonic stem cell (ESC) and neural progenitor
      cell (NPC). We demonstrated that the H3K27me3 DHMSs identified by our approach
      are of high sensitivity, specificity, and technical reproducibility. ChIPDiff was
      further applied to uncover the differential H3K4me3 and H3K36me3 sites between
      different cell states. The result showed significant correlation between the
      histone modification states and the gene expression levels.

PMID- 22130889
TI  - ChIP-Seq data analysis: identification of protein-DNA binding sites with SISSRs
      peak-finder.
AB  - Protein-DNA interactions play key roles in determining gene-expression programs
      during cellular development and differentiation. Chromatin immunoprecipitation
      (ChIP) is the most widely used assay for probing such interactions. With recent
      advances in sequencing technology, ChIP-Seq, an approach that combines ChIP and
      next-generation parallel sequencing is fast becoming the method of choice for
      mapping protein-DNA interactions on a genome-wide scale. Here, we briefly review
      the ChIP-Seq approach for mapping protein-DNA interactions and describe the use
      of the SISSRs peak-finder, a software tool for precise identification of protein
      DNA binding sites from sequencing data generated using ChIP-Seq.

PMID- 22130890
TI  - Using ChIPMotifs for de novo motif discovery of OCT4 and ZNF263 based on ChIP
      based high-throughput experiments.
AB  - DNA motifs are short sequences varying from 6 to 25 bp and can be highly variable
      and degenerated. One major approach for predicting transcription factor (TF)
      binding is using position weight matrix (PWM) to represent information content of
      regulatory sites; however, when used as the sole means of identifying binding
      sites suffers from the limited amount of training data available and a high rate
      of false-positive predictions. ChIPMotifs program is a de novo motif finding tool
      developed for ChIP-based high-throughput data, and W-ChIPMotifs is a Web
      application tool for ChIPMotifs. It composes various ab initio motif discovery
      tools such as MEME, MaMF, Weeder and optimizes the significance of the detected
      motifs by using bootstrap re-sampling error estimation and a Fisher test. Using
      these techniques, we determined a PWM for OCT4 which is similar to canonical OCT4
      consensus sequence. In a separate study, we also use de novo motif discovery to
      suggest that ZNF263 binds to a 24-nt site that differs from the motif predicted
      by the zinc finger code in several positions.

PMID- 22130891
TI  - Hidden Markov models for controlling false discovery rate in genome-wide
      association analysis.
AB  - Genome-wide association studies (GWAS) have shown notable success in identifying
      susceptibility genetic variants of common and complex diseases. To date, the
      analytical methods of published GWAS have largely been limited to single single
      nucleotide polymorphism (SNP) or SNP-SNP pair analysis, coupled with multiplicity
      control using the Bonferroni procedure to control family wise error rate (FWER).
      However, since SNPs in typical GWAS are in linkage disequilibrium, simple
      Bonferonni correction is usually over conservative and therefore leads to a loss
      of efficiency. In addition, controlling FWER may be too stringent for GWAS where
      the number of SNPs to be tested is enormous. It is more desirable to control the
      false discovery rate (FDR). We introduce here a hidden Markov model (HMM)-based
      PLIS testing procedure for GWAS. It captures SNP dependency by an HMM, and based
      which, provides precise FDR control for identifying susceptibility loci.

PMID- 22130892
TI  - Employing gene set top scoring pairs to identify deregulated pathway-signatures
      in dilated cardiomyopathy from integrated microarray gene expression data.
AB  - It is well accepted that a set of genes must act in concert to drive various
      cellular processes. However, under different biological phenotypes, not all the
      members of a gene set will participate in a biological process. Hence, it is
      useful to construct a discriminative classifier by focusing on the core members
      (subset) of a highly informative gene set. Such analyses can reveal which of
      those subsets from the same gene set correspond to different biological
      phenotypes. In this study, we propose Gene Set Top Scoring Pairs (GSTSP) approach
      that exploits the simple yet powerful relative expression reversal concept at the
      gene set levels to achieve these goals. To illustrate the usefulness of GSTSP, we
      applied this method to five different human heart failure gene expression data
      sets. We take advantage of the direct data integration feature in the GSTSP
      approach to combine two data sets, identify a discriminative gene set from >190
      predefined gene sets, and evaluate the predictive power of the GSTSP classifier
      derived from this informative gene set on three independent test sets (79.31% in
      test accuracy). The discriminative gene pairs identified in this study may
      provide new biological understanding on the disturbed pathways that are involved
      in the development of heart failure. GSTSP methodology is general in purpose and
      is applicable to a variety of phenotypic classification problems using gene
      expression data.

PMID- 22130893
TI  - JAMIE: A software tool for jointly analyzing multiple ChIP-chip experiments.
AB  - Chromatin immunoprecipitation followed by genome tiling array hybridization (ChIP
      chip) is a powerful approach to map transcription factor binding sites (TFBSs).
      Similar to other high-throughput genomic technologies, ChIP-chip often produces
      noisy data. Distinguishing signals from noise in these data is challenging. ChIP
      chip data in public databases are rapidly growing. It is becoming more and more
      common that scientists can find multiple data sets for the same transcription
      factor in different biological contexts or data for different transcription
      factors in the same biological context. When these related experiments are
      analyzed together, binding site detection can be improved by borrowing
      information across data sets. This chapter introduces a computational tool JAMIE
      for Jointly Analyzing Multiple ChIP-chip Experiments. JAMIE is based on a
      hierarchical mixture model, and it is implemented as an R package. Simulation and
      real data studies have shown that it can significantly increase sensitivity and
      specificity of TFBS detection compared to existing algorithms. The purpose of
      this chapter is to describe how the JAMIE package can be used to perform the
      integrative data analysis.

PMID- 22130894
TI  - Epigenetic analysis: ChIP-chip and ChIP-seq.
AB  - The access of transcription factors and the replication machinery to DNA is
      regulated by the epigenetic state of chromatin. In eukaryotes, this complex layer
      of regulatory processes includes the direct methylation of DNA, as well as
      covalent modifications to histones. Using next-generation sequencers, it is now
      possible to obtain profiles of epigenetic modifications across a genome using
      chromatin immunoprecipitation followed by sequencing (ChIP-seq). This technique
      permits the detection of the binding of proteins to specific regions of the
      genome with high resolution. It can be used to determine the target sequences of
      transcription factors, as well as the positions of histones with specific
      modification of their N-terminal tails. Antibodies that selectively bind
      methylated DNA may also be used to determine the position of methylated
      cytosines. Here, we present a data analysis pipeline for processing ChIP-seq
      data, and discuss the limitations and idiosyncrasies of these approaches.

PMID- 22130895
TI  - BiNGS!SL-seq: a bioinformatics pipeline for the analysis and interpretation of
      deep sequencing genome-wide synthetic lethal screen.
AB  - While targeted therapies have shown clinical promise, these therapies are rarely
      curative for advanced cancers. The discovery of pathways for drug compounds can
      help to reveal novel therapeutic targets as rational combination therapy in
      cancer treatment. With a genome-wide shRNA screen using high-throughput genomic
      sequencing technology, we have identified gene products whose inhibition
      synergizes with their target drug to eliminate lung cancer cells. In this
      chapter, we described BiNGS!SL-seq, an efficient bioinformatics workflow to
      manage, analyze, and interpret the massive synthetic lethal screen data for
      finding statistically significant gene products. With our pipeline, we identified
      a number of druggable gene products and potential pathways for the screen in an
      example of lung cancer cells.

PMID- 22130896
TI  - Folding of an all-helical Greek-key protein monitored by quenched-flow hydrogen
      deuterium exchange and NMR spectroscopy.
AB  - To advance our understanding of the protein folding process, we use stopped-flow
      far-ultraviolet (far-UV) circular dichroism and quenched-flow hydrogen-deuterium
      exchange coupled with nuclear magnetic resonance (NMR) spectroscopy to monitor
      the formation of hydrogen-bonded secondary structure in the C-terminal domain of
      the Fas-associated death domain (Fadd-DD). The death domain superfamily fold
      consists of six alpha-helices arranged in a Greek-key topology, which is shared
      by the all-beta-sheet immunoglobulin and mixed alpha/beta-plait superfamilies.
      Fadd-DD is selected as our model death domain protein system because the
      structure of this protein has been solved by NMR spectroscopy, and both
      thermodynamic and kinetic analysis indicate it to be a stable, monomeric protein
      with a rapidly formed hydrophobic core. Stopped-flow far-UV circular dichroism
      spectroscopy revealed that the folding process was monophasic and the rate is
      23.4 s(-1). Twenty-two amide hydrogens in the backbone of the helices and two in
      the backbone of the loops were monitored, and the folding of all six helices was
      determined to be monophasic with rate constants between 19 and 22 s(-1). These
      results indicate that the formation of secondary structure is largely cooperative
      and concomitant with the hydrophobic collapse. This study also provides
      unprecedented insight into the formation of secondary structure within the highly
      populated Greek-key fold more generally. Additional insights are gained by
      calculating the exchange rates of 23 residues from equilibrium hydrogen-deuterium
      exchange experiments. The majority of protected amide protons are found on
      helices 2, 4, and 5, which make up core structural elements of the Greek-key
      topology.

PMID- 22130898
TI  - Methods of suicide used by children and adolescents.
AB  - Although relatively rare, suicide is a leading cause of death in children and
      adolescents in the Western world. This study examined whether children and
      adolescents are drawn to other methods of suicide than adults. Swiss suicides
      from 1998 to 2007 were examined. The main methods of suicide were analysed with
      respect to age and gender. Of the 12,226 suicides which took place in this 10
      year period, 333 were committed by children and adolescents (226 males, 107
      females). The most prevalent methods of suicide in children and adolescents 0-19
      years were hanging, jumping from heights and railway-suicides (both genders),
      intoxication (females) and firearms (males). Compared to adults, railway-suicides
      were over-represented in young males and females (both P < .001). Jumping from
      heights was over-represented in young males (P < .001). Thus, availability has an
      important effect on methods of suicide chosen by children and adolescents.
      Restricting access to most favoured methods of suicide might be an important
      strategy in suicide prevention.

PMID- 22130899
TI  - Left atrial speckle tracking analysis in patients with mitral insufficiency and
      history of paroxysmal atrial fibrillation.
AB  - The occurrence of atrial fibrillation (AF), especially in patients with mitral
      regurgitation (MR), is related to the degree of left atrial (LA) myopathy,
      remodeling and fibrosis, that are responsible of LA electrical inhomogeneity and
      abnormal conduction velocities. Speckle tracking echocardiography (STE) has
      recently enabled the quantification of longitudinal myocardial LA deformation
      dynamics. Our aim was to investigate by STE the effects of the occurrence of
      paroxysmal AF on LA myocardial deformation, in a population of patients with
      asymptomatic chronic MR. We compared two groups of a total of 197 patients with
      MR: 54 with history of paroxysmal AF and 143 with MR alone. Subgroups were
      created according to MR degree. Peak atrial longitudinal strain (PALS) was
      measured in all subjects. Values were obtained by averaging all segments (global
      PALS), measured in the 4-chamber and 2-chamber views. Compared to the mild MR
      group (46.1 +/- 4.9%), global PALS was lower in moderate MR group (22.1 +/- 5.8%)
      and further reduced in the severe MR group (13.9 +/- 4.2%; overall P < 0.0001 by
      ANOVA, P < 0.05 for all pair-wise comparisons). Besides, in each MR group,
      patients with history of paroxysmal AF presented a global PALS significantly
      reduced (overall P < 0.0001 by ANOVA). After multivariate analysis, global PALS
      was significantly and independently associated with paroxysmal AF. STE enables
      noninvasive quantification of LA dysfunction due to MR and paroxysmal AF. MR have
      a major negative impact on LA function. In patients with MR, the history of
      paroxysmal AF is associated to a further impair of LA myocardial reservoir
      function.

PMID- 22130900
TI  - Animal models of dyssynchrony.
AB  - Cardiac resynchronization therapy (CRT) is an important therapy for patients with
      heart failure and conduction pathology, but the benefits are heterogeneous
      between patients and approximately a third of patients do not show signs of
      clinical or echocardiographic response. This calls for a better understanding of
      the underlying conduction disease and resynchronization. In this review, we
      discuss to what extent established and novel animal models can help to better
      understand the pathophysiology of dyssynchrony and the benefits of CRT.

PMID- 22130901
TI  - Designing hybrid foldamers: the effect on the peptide conformational bias of beta
      versus alpha- and gamma-linear residues in alternation with (1R,2S)-2
      aminocyclobutane-1-carboxylic acid.
AB  - Several oligomers constructed with (1R,2S)-2-aminocyclobutane-1-carboxylic acid
      and glycine, beta-alanine, and gamma-amino butyric acid (GABA), respectively,
      joined in alternation have been synthesized and studied by means of NMR and CD
      experiments as well as with computational calculations. Results account for the
      spacer length effect on folding and show that conformational preference for these
      hybrid peptides can be tuned from beta-sheet-like folding for those containing a
      C(2) or C(4) linear segment to a helical folding for those with a C(3) spacer
      between cyclobutane residues. The introduction of cyclic spacers between these
      residues does not modify the extended ribbon-type structure previously manifested
      in poly(cis-cyclobutane) beta-oligomers.

PMID- 22130902
TI  - Effect of EpCAM, CD44, CD133 and CD166 expression on patient survival in tumours
      of the ampulla of Vater.
AB  - BACKGROUND: Carcinomas of the Vaterian system are rare and presumably arise from
      pre-existing adenomas. According to the cancer stem cell (CSC) hypothesis, only a
      small subset of tumor cells has the ability to initiate and develop tumor growth.
      In colorectal cancer, CD44, CD133, CD166 and EpCAM have been proposed to
      represent CSC marker proteins and their expression has been shown to correlate
      with patient survival. AIMS: To evaluate a potential role of these CSC proteins
      in tumors of the ampulla of Vater, we investigated their expression in 175
      carcinoma, 111 adenoma and 152 normal mucosa specimens arranged in a Tissue
      Microarray format. MATERIALS AND METHODS: Membranous immunoreactivity for each
      protein marker was scored semi-quantitatively by evaluating the number of
      positive tumor cells over the total number of tumor cells. Median protein
      expression levels were used as cut-off scores to define protein marker
      positivity. Clinical data including survival time were obtained by retrospective
      analysis of medical records, tumor registries or direct contact. RESULTS: The
      expression of all evaluated marker proteins differed significantly between normal
      mucosa, adenoma and carcinoma samples. In all markers, we found a tendency
      towards more constant expression from normal to neoplastic tissue. EpCAM
      expression was significantly correlated with better patient survival. The
      increased expression of CD44s, CD166 and CD133 from normal mucosa samples to
      adenoma and carcinoma was linked to tumor progression. However, there was no
      statistically significant correlation with survival. CONCLUSION: Our findings
      indicate, that in ampullary carcinomas, loss of expression of EpCAM may be linked
      to a more aggressive tumor phenotype.

PMID- 22130903
TI  - Standardisation of EGFR FISH in colorectal cancer: results of an international
      interlaboratory reproducibility ring study.
AB  - AIMS: Epidermal growth factor receptor (EGFR) gene copy number evaluated by
      fluorescence in situ hybridisation (FISH) can discriminate among KRAS wild-type
      patients those with better outcome to EGFR-targeted therapy in metastatic
      colorectal cancer, further enhancing selection of patients. Nevertheless,
      enumeration of gene copies is challenging and the lack of analytical
      standardisation has limited incorporation of the test into the clinical practice.
      We therefore assessed EGFR FISH interlaboratory consensus among five molecular
      diagnostic reference centres. METHODS: A set of 12 colorectal cancer samples
      circulated among laboratories, and samples were scored according to commonly
      agreed guidelines. Reproducibility was quantified using the standard error of
      measurement (SEM). RESULTS: A SEM of 0.865 and a within-subject coefficient of
      variation (WSCV) of 26.8% for mean EGFR gene/nuclei and a SEM of 0.235 and a WSCV
      of 19.4% for the mean EGFR gene/CEP7 ratio were observed. Measurement of the
      fraction of cells displaying chromosome 7 polysomy showed WSCV of 46.6%, 34.0%
      and 51.0% for percentage of cells displaying <=2, >=3 and >=4 EGFR signals,
      respectively. Among different slides of the same specimen, the WSCV was 6.1% for
      mean EGFR gene/nuclei and 3.9% for mean of EGFR gene/CEP7 ratios. CONCLUSIONS:
      Molecular diagnosis of EGFR gene copy number by FISH varied largely among
      pathology centres, with fluctuations covering the whole range of proposed cut
      offs of predictive usefulness from literature. Definition of a detailed scoring
      system and implementation of comprehensive training programmes for laboratories
      are therefore necessary before including the test into clinical practice.

PMID- 22130904
TI  - Mobile assessment in schizophrenia: a data-driven momentary approach.
AB  - In this article, a data-driven approach was adopted to demonstrate how real-life
      diary techniques [ie, the experience sampling method (ESM)] could be deployed for
      assessment purposes in patients with psychotic disorder, delivering
      individualized and clinically relevant information. The dataset included patients
      in an acute phase of psychosis and the focus was on paranoia as one of the main
      psychotic symptoms (30 patients with high levels of paranoia and 34 with low
      levels of paranoia). Based on individual cases, it was demonstrated how (1)
      symptom and mood patterns, (2) patterns of social interactions or activities, (3)
      contextual risk profiles (eg, is being among strangers, as opposed to family,
      associated with higher paranoia severity?), and (4) temporal dynamics between
      mood states and paranoia (eg, does anxiety precipitate or follow the onset of
      increased paranoia severity?) substantially differ within individual patients and
      across the high vs low paranoid patient group. Most striking, it was shown that
      individual findings are different from what is found on overall group levels.
      Some people stay anxious after a paranoid thought came to mind. For others,
      paranoia is followed by a state of relaxation. It is discussed how ESM, surfacing
      the patient's implicit knowledge about symptom patterns, may provide an excellent
      starting point for person-tailored psychoeducation and for choosing the most
      applicable therapeutic intervention.

PMID- 22130905
TI  - A randomized controlled trial of relapse prevention therapy for first-episode
      psychosis patients: outcome at 30-month follow-up.
AB  - The effectiveness of a novel 7-month psychosocial treatment designed to prevent
      the second episode of psychosis was evaluated in a randomized controlled trial at
      2 specialist first-episode psychosis (FEP) programs. An individual and family
      cognitive behavior therapy for relapse prevention was compared with specialist
      FEP care. Forty-one FEP patients were randomized to the relapse prevention
      therapy (RPT) and 40 to specialist FEP care. Participants were assessed on an
      array of measures at baseline, 7- (end of therapy), 12-, 18-, 24-, and 30-month
      follow-up. At 12-month follow-up, the relapse rate was significantly lower in the
      therapy condition compared with specialized treatment alone (P = .039), and time
      to relapse was significantly delayed for those in the relapse therapy condition
      (P = .038); however, such differences were not maintained. Unexpectedly,
      psychosocial functioning deteriorated over time in the experimental but not in
      the control group; these differences were no longer statistically significant
      when between-group differences in medication adherence were included in the
      model. Further research is required to ascertain if the initial treatment effect
      of the RPT can be sustained. Further research is needed to investigate if
      medication adherence contributes to negative outcomes in functioning in FEP
      patients who have reached remission, or, alternatively, if a component of RPT is
      detrimental.

PMID- 22130906
TI  - Osteoporotic vertebral fractures: current concepts of conservative care.
AB  - INTRODUCTION: Osteoporotic vertebral compression fractures (VCFs) are a growing
      public health problem with important socio-economic effects in western countries.
      In the USA, 10 million people over 50 suffer from osteoporosis. In these
      patients, 1.5 million annual fractures have been registered, and 50% of these are
      vertebral compression. SOURCES OF DATA: We performed a comprehensive search of
      PubMed, Medline, Cochrane, CINAHL and Embase databases using various combinations
      of the keywords 'osteoporosis', 'vertebral compression fractures', 'brace',
      'bracing', 'orthosis', 'conservative management' and 'rehabilitation' over the
      years 1966-2011. All articles relevant to the subject were retrieved, and their
      bibliographies were hand searched for further references in the context of
      conservative management of osteoporotic vertebral fractures. AREAS OF AGREEMENT:
      Conservative management for patients with osteoporotic vertebral fractures
      includes bed rest, pain medication, physiotherapy and bracing. AREAS OF
      CONTROVERSY: A conservative management for patients with osteoporotic VCFs s has
      not been standardized. The utility of vertebral augmentation techniques has been
      questioned by recent randomized controlled trials. GROWING POINTS: Randomized
      controlled trials are being performed worldwide on vertebral augmentation
      techniques. AREAS TIMELY FOR DEVELOPING RESEARCH: Although spinal orthoses are
      commonly used for the management of patients with osteoporotic vertebral
      fractures, in the literature there is only one randomized controlled trial on
      bracing for this condition. While the best conservative management for subjects
      with osteoporotic VCFs s is not defined and standardized, no conclusions on the
      superiority of vertebral augmentation techniques over conservative management can
      be drawn.

PMID- 22130907
TI  - Postnatal depression and its effects on child development: a review of evidence
      from low- and middle-income countries.
AB  - INTRODUCTION OR BACKGROUND: It is well established that postnatal depression
      (PND) is prevalent in high-income countries and is associated with negative
      personal, family and child developmental outcomes. SOURCES OF DATA: Here, studies
      on the prevalence of maternal PND in low- and middle-income countries are
      reviewed and a geographical prevalence map is presented. The impact of PND upon
      child outcomes is also reviewed. AREAS OF AGREEMENT: The available evidence
      suggests that rates of PND are substantial, and in many regions, are higher than
      those reported for high-income countries. An association between PND and adverse
      child developmental outcomes was identified in many of the countries examined.
      AREAS OF CONTROVERSY: Significant heterogeneity in prevalence rates and impact on
      child outcomes across studies means that the true extent of the disease burden is
      still unclear. AREAS TIMELY FOR DEVELOPING RESEARCH: Nonetheless, there is a
      compelling case for the implementation of interventions to reduce the impact of
      PND on the quality of the mother-infant relationship and improve child outcomes.

PMID- 22130908
TI  - Immunologic characteristics of intrarenal T cells: trafficking of expanded CD8+ T
      cell beta-chain clonotypes in progressive lupus nephritis.
AB  - OBJECTIVE: To better define the immunologic character of the T cell infiltrate in
      lupus nephritis. METHODS: We performed double immunohistochemical staining and
      clonotypic T cell receptor (TCR) beta-chain sequencing in multiple anatomic
      regions isolated by laser-capture microdissection from renal biopsy samples.
      RESULTS: Systemic lupus erythematosus (SLE) kidneys have a variably patterned and
      often extensive infiltrate of predominantly clonally expanded T cells of CD4 and
      CD8 lineages. CD4+ T cells were prominent in nearly two-thirds of SLE biopsy
      samples and were distributed as broad periglomerular aggregates or intermixed
      with CD8+ T cells forming periglomerular caps. Sequencing of the TCR from
      periglomerular regions showed a predominance of clonally expanded T cells. The
      CD8+ T cells, which were present in all biopsy samples, often adhered to Bowman's
      capsule and infiltrated the tubular epithelium. They exhibited features that
      suggest participation in an adaptive immune response: differentiation into
      CD28(null)  memory-effector phenotype, trafficking of the same expanded clonotype
      to different regions of the kidney and to the peripheral blood, and clonal
      persistence for years in repeat biopsy samples. CD8+ T cell tubulitis was
      especially associated with progressive changes. CONCLUSION: The immunologic
      characteristics of the infiltrating CD4+ and CD8+ T cells in the lupus kidney
      indicate that they have the potential to mediate injury, which may be relevant to
      development of progressive renal failure. Whereas the oligoclonality of the CD4+
      T cell infiltrate is consistent with the paradigm of SLE as a class II major
      histocompatibility complex-associated autoimmune disease, the finding of CD8+ T
      cell clonality and trafficking implies participation in a distinct systemic
      adaptive immune response.

PMID- 22130909
TI  - Kinematic and electromyographic studies on unaided, unilateral and bilateral
      crutch walking in adolescents with spastic diplegia.
AB  - BACKGROUND: Back pain and ambulation deterioration among ambulatory individuals
      with cerebral palsy (CP) are common as they grow older and walking aids are often
      prescribed to improve stability and promote maximal weight-bear on lower limbs
      during gait. OBJECTIVE: To investigate the effects of walking aids on back muscle
      activity and whole body kinematics among adolescents with spastic diplegia. STUDY
      DESIGN: A repeated-measures design was adopted with participants tested under
      different walking conditions. METHODS: Ten participants were recruited and
      Lofstrand forearm crutches were selected. Both the activity of lumbar erector
      spinae and the kinematics of head, trunk, pelvis and lower limbs during walking
      were monitored using telemetric electromyography and motion analysis system
      respectively. RESULTS: Comparisons between walking unaided and walking with
      unilateral and bilateral crutch(es) were made. Significant decreases in speed,
      cadence, erector spinae activity and lower trunk extension were observed during
      crutch walking together with significantly increased stride time and anterior
      pelvic tilt. CONCLUSIONS: These findings suggested that Lofstrand crutch(es)
      reduced muscular demands and lumbar lordosis with increased lower back mobility.
      The results shed light on the prescription of walking aid in the management and
      prevention of chronic back pain for ambulatory individuals with CP from a life
      span perspective.

PMID- 22130910
TI  - The effect of floor reaction ankle foot orthosis on postural control in children
      with spastic cerebral palsy.
AB  - BACKGROUND: Children with cerebral palsy (CP) often demonstrate postural control
      difficulties. Orthotic management may assist in improving postural control in
      these children. OBJECTIVE: The purpose of this investigation was to examine the
      influence of floor reaction ankle foot orthosis (FRAFO) on postural flexion
      called the crouch position in children with CP. STUDY DESIGN: Quasi-experimental.
      METHODS: Eight children with spastic diplegic CP and eight matched typically
      developing children participated in this study. Postural control of children with
      CP was assessed in a static standing position on a force platform with/without a
      FRAFO. The parameters used were centre of pressure (CoP) measures, calculated
      from force platform signals including the standard deviation (SD) of excursion;
      phase plate portrait and SD of velocity in anteroposterior (AP) and mediolateral
      (ML) directions. RESULTS: The maximum knee extension was statistically
      significant in children with CP when barefoot compared to wearing braced footwear
      (p < 0.05, t = 10.01). AP and ML displacement, AP velocity and AP phase plate
      portrait of CoP were not statistically significant between children with CP
      with/without a FRAFO (p < 0.05). CONCLUSION: FRAFO can improve the alignment of
      the knee, but may not be helpful in improving postural control in children with
      CP in a short time period.

PMID- 22130911
TI  - Effect of insole material on lower limb kinematics and plantar pressures during
      treadmill walking.
AB  - BACKGROUND: Currently there is a paucity of research providing recommendations on
      the type of orthotic or material used in its construction for different patient
      requirements. OBJECTIVES: To gain a greater understanding of the characteristics
      of orthotic materials and how they affect gait so to enhance the clinical
      decision-making process. STUDY DESIGN: Repeated measures. METHODS: Plantar
      pressures and kinematics were evaluated for 10 participants while walking on a
      treadmill under various conditions which included, shoes only and shoes with four
      different flat insoles and custom devices created in each of two densities of two
      materials. RESULTS: For the flat insoles, medium density ethyl vinyl acetate was
      found to produce greater peak pressures than at least one of the other material
      conditions and low and medium density polyurethane were most effective at
      increasing average contact area and at reducing pressure time integral. For the
      custom devices, while no significant differences were evident, when compared to
      the shoe only condition, medium density polyurethane increased average contact
      area by a greater percentage than the other materials. CONCLUSIONS: Results for
      medium density polyurethane suggest a possible difference in loading
      characteristics, indicating a potential material suitability for patients with a
      compromised ability to deal with pressure.

PMID- 22130912
TI  - Treatment for chemotherapy-induced alopecia in mice using parathyroid hormone
      agonists and antagonists linked to a collagen binding domain.
AB  - Parathyroid hormone (PTH) agonists and antagonists have been shown to improve
      hair growth after chemotherapy; however, rapid clearance and systemic side
      effects complicate their usage. To facilitate delivery and retention to skin, we
      fused PTH agonists and antagonists to the collagen binding domain (CBD) of
      Clostridium histolyticum collagenase. in-vitro studies showed that the agonist
      fusion protein, PTH-CBD, bound collagen and activated the PTH/parathyroid hormone
      related peptide receptor in SaOS-2 cells. The antagonist fusion proteins, PTH(7
      33)-CBD and PTH([-1]-33)-CBD, also bound collagen and antagonized PTH(1-34)
      effect in SaOS-2 cells; however, PTH(7-33)-CBD had lower intrinsic activity.
      Distribution studies confirmed uptake of PTH-CBD to the skin at 1 and 12 hr after
      subcutaneous injection. We assessed in vivo efficacy of PTH-CBD and PTH(7-33)-CBD
      in C57BL/6J mice. Animals were depilated to synchronize the hair follicles;
      treated on Day 7 with agonist, antagonist, or vehicle; treated on Day 9 with
      cyclophosphamide (150 mg/kg i.p.) or vehicle; and sacrificed on Day 39. Normal
      mice (no chemo and no treatment) showed rapid regrowth of hair and normal
      histology. Chemo+Vehicle mice showed reduced hair regrowth and decreased
      pigmentation; histology revealed reduced number and dystrophic anagen/catagen
      follicles. Chemo+Antagonist mice were grossly and histologically
      indistinguishable from Chemo+Vehicle mice. Chemo+Agonist mice showed more rapid
      regrowth and repigmentation of hair; histologically, there was a normal number of
      hair follicles, most of which were in the anagen phase. Overall, the agonist PTH
      CBD had prominent effects in reducing chemotherapy-induced damage of hair
      follicles and may show promise as a therapy for chemotherapy-induced alopecia.

PMID- 22130913
TI  - Supracricoid laryngectomy with cricohyoidopexy: oncological results.
AB  - This study assessed the oncological results in patients undergoing supracricoid
      laryngectomy with cricohyoidopexy. A cohort of 44 patients surgically treated
      using supracricoid laryngectomy with cricohyoidopexy between June 2001 and
      December 2009 was retrospectively analyzed. The mean follow-up period was 53.2
      (+/-24.7) months. The Kaplan-Meier method was used to analyze overall survival
      and disease-specific survival, as well as survival according to T2 and T3
      subgroups. Overall survival rates at 3 and 5 years were 90.5 and 84.1%,
      respectively. The 3- and 5-year disease-specific survival rates were 95.4 and
      92.5%, respectively. Overall survival for patients with T2 disease was 87.5% at 3
      years and 80.8% at 5 years. For T3, the corresponding rates were 91.8 and 87.0%.
      Disease-specific survival for patients with T2 disease was 93.3% at 3 years and
      the same at 5 years; the corresponding rates for T3 were 96.4 and 91.4%. The
      differences between T2 and T3 patients at 3 and 5 years with respect to overall
      and disease-specific survival were not statistically significant (P = 0.903 and P
      = 0.863, respectively). Recurrence was local in one patient (2.2%) and regional
      in three (6.8%). There were three distant metastases (6.8%) and one second
      primary carcinoma (2.2%). These findings support the use of supracricoid
      laryngectomy with cricohyoidopexy as an oncologically safe technique in properly
      selected patients with laryngeal carcinoma.

PMID- 22130914
TI  - Bicanalicular double silicone stenting in endoscopic dacryocystorhinostomy with
      lacrimal trephination in distal or common canalicular obstruction.
AB  - The purpose of the study was to evaluate the clinical effects of bicanalicular
      double silicone stents in endoscopic transnasal dacryocystorhinostomy with
      lacrimal trephinized canaliculoplasty for monocanalicular and common canalicular
      obstruction. Bicanalicular double silicone intubation in endoscopic transnasal
      dacryocystorhinostomy with lacrimal trephination was performed in 58 eyes of 54
      patients (5 men, 49 women; mean age: 55.9 +/- 14.9 years) with epiphora due to
      monocanalicular and common canalicular obstruction between November 2007 and
      August 2010. We reviewed the records of subjects who had undergone the same
      surgery with a bicanalicular single intubation for same disease between March
      2004 and October 2007 as controls (56 eyes of 50 patients). We evaluated age,
      gender, the operative side, the site of canalicular obstruction, and the effects
      of double silicone intubation. Complications relating to the silicone tube were
      also investigated. The double-stent group showed higher anatomical success rates
      (91.4%) and functional success rates (82.8%) than the single-stent group (75.0
      and 69.6%, respectively) (p = 0.034 and p = 0.103, respectively). Bicanalicular
      double silicone stenting in endoscopic transnasal dacryocystorhinostomy with
      lacrimal trephinized canaliculoplasty may be an effective treatment for
      monocanalicular and common canalicular obstructions. This may also reduce more
      invasive surgery including Jones tube insertion (p = 0.038).

PMID- 22130915
TI  - Postoperative pain assessment after septorhinoplasty.
AB  - Postoperative pain after septorhinoplasty and its optimal management has not been
      described in detail. Fifty-two adult septorhinoplasty patients were included in a
      prospective cohort single center study. Patients' and surgical characteristics
      were evaluated. Outcome and process parameters were analyzed using the
      questionnaires of the German-wide project Quality Improvement in Postoperative
      Pain Management (QUIPS) on the first postoperative day. Pain during the first
      operative day after septorhinoplasty was moderate. Pain management predominately
      consisted of remifentanil intraoperatively, metamizole in the recovery room, in
      combination with piritramide in one-third of the patients, and metamizole on
      ward. Patients younger than 31 years were less satisfied with pain management (P
      = 0.018). Open rhinoplasty was associated with less satisfaction with pain
      management (P = 0.007). Use of rib grafts led to more mobility, breathing,
      sleeping and mood disturbances (P = 0.003, 0.047; 0.047; 0.022, respectively).
      Preoperative pain counseling was followed by higher satisfaction, less breathing
      and mood disturbances after surgery (P = 0.021; 0.004; 0.046, respectively).
      Opioids in the recovery room in addition to non-opioids and treatment with non
      opioids on ward led to less maximal pain (P = 0.027 and 0.040, respectively). We
      conclude that QUIPS is an easy tool to evaluate the quality of postoperative pain
      management following rhinoplasty. Preoperative pain counseling, specific care for
      patients with rib grafts, consequent use of opioids in the recovery room in
      addition to non-opioids, and use of non-opioids on ward seem to be effective to
      improve pain management after septorhinoplasty.

PMID- 22130916
TI  - Impact of ozone exposure on prostaglandin release in nasal polyps.
AB  - A dysregulation of the cyclooxygenases and a leukotriene/prostaglandin imbalance
      are assumed to be part of the pathogenesis of the aspirin (ASA) intolerance
      syndrome. Ozone is an air pollutant with known proinflammatory effects on exposed
      epithelia, however, its impact on the expression of the cyclooxygenases 1 and 2
      (cox1/2) and prostaglandin E(2) (PGE(2)) in the nasal mucosa is not well known.
      Therefore, we analyzed cox expression and PGE(2) levels after ozone exposure in
      nasal mucosa and in nasal polyps considering ASA intolerance. Isolated epithelial
      nasal cells from control subjects without chronic rhinosinusitis (CRS), and those
      from patients with nasal polyps with and without ASA intolerance were cultured
      and exposed in vitro to ozone. Cox1/2 expression levels were analyzed by
      immunohistochemistry and PGE(2) release by ELISA. After ozone exposure cox1/2
      expression remained unchanged in all the three groups. PGE(2) release was lowered
      in cell cultures from controls and from polyps of ASA tolerant but not in those
      of ASA intolerant patients after ozone exposure. In the latter, PGE(2) expression
      remained unchanged. Our in vitro data suggest that aspirin tolerant patients with
      polyps might be more affected by ozone compared to aspirin intolerant ones. The
      potential clinical impact of impaired PGE(2) expression caused by ozone on the
      functions of respiratory epithelia remains to be clarified.

PMID- 22130917
TI  - No evidence for disturbed COL1A1 and A2 expression in otosclerosis.
AB  - Otosclerosis is a complex bone remodeling disorder of the human otic capsule that
      might be associated with various mutations of A1 and A2 alleles of type-I
      collagen. The study herein presented, investigates the possibilty of the genetic
      involvement of type-I collagen in the pathogenesis of histologically confirmed
      otosclerosis. A total of 55 ankylotic stapes footplates were analyzed. Cortical
      bone fragments (n = 30), incus (n = 3) and malleus (n = 2) specimens were
      employed as negative controls. Specimens were divided into two groups. The first
      group was processed using conventional H.E. hematoxylin-eosin (H.E.) staining and
      type-I collagen-specific immunofluorescent assay (IFA), while the second group
      was examined by COL1A1 and A2-specific RT-PCR. Otosclerotic- (n = 31) and non
      otosclerotic stapes footplates (n = 9) as well as cortical bones (n = 20), incus
      (n = 2) and malleus specimens (n = 1) showed normal and quite similar A1 and A2
      allele expression confirmed by IFA. RT-PCR analysis revealed normal and
      consistent mRNA expression of both alleles in each specimen. Expression levels
      and patterns of COL1A1/A2 alleles did not show significant correlation with the
      histological diagnosis of otosclerosis. Type-I collagen is a highly conserved
      structure protein, which plays a fundamental role in the integritiy of various
      connective tissues. Mutations of A1 and A2 alleles result in serious systemic
      disorders of the skeleton, tendons and skin. Since otosclerosis is an organ
      specific disease, it is difficult to explain its genetic association with type-I
      collagen. In conclusion, we found no evidence supporting the putative link of
      COL1A1 and COL1A2 alleles with otosclerosis.

PMID- 22130918
TI  - Primary human osteoblast cultures.
AB  - Osteoblast cultures can be used to investigate the mechanisms of bone formation,
      to probe the cellular and molecular basis of bone disease, and to screen for
      potential therapeutic agents that affect bone formation. Here, we describe the
      methods for establishing and characterising primary human osteoblast cultures.

PMID- 22130919
TI  - Osteoblast isolation from murine calvaria and long bones.
AB  - This chapter describes the isolation of primary mouse osteoblasts from adult
      mouse calvaria and long bones, as well as the process of isolation of bone cells
      from neonatal mouse calvaria. Osteoblasts from adult mouse bone are obtained as
      outgrowth from collagenase-treated bone pieces. Isolation of osteoblasts from
      neonatal calvaria is achieved by sequential enzymatic digestion of the bone
      matrix. Because of differences in origin and isolation method, each of the
      primary bone cell cultures described will have their own characteristics.

PMID- 22130920
TI  - Rat osteoblast cultures.
AB  - This chapter describes the isolation, culture and staining of primary osteoblasts
      from the calvaria and long bones of neonatal rats. The key advantages of this
      assay are that it allows direct measurement of bone matrix deposition and
      mineralisation, as well as yielding good quantities of osteoblasts at defined
      stages of differentiation for molecular and histological analysis. A special
      focus of this chapter is on the role of beta-glycerophosphate in cell-mediated
      mineralisation in these cultures.

PMID- 22130921
TI  - Isolation of primary avian osteocytes.
AB  - Osteocytes can be isolated from chicken calvaria using mild EDTA treatment
      alternating with collagenase treatment. The cell population obtained contains
      both osteoblasts and osteocytes. A pure population of osteocytes is obtained
      following immunomagnetic separation with the osteocyte-specific monoclonal
      antibody MAb OB7.3.

PMID- 22130922
TI  - Isolation of mouse osteocytes using cell fractionation for gene expression
      analysis.
AB  - Osteocytes are the terminally differentiated cells of the osteoblastic lineage
      embedded within the mineralized bone matrix. T: hey have been identified as key
      players in mechanotransduction and in mineral and phosphate homeostasis. In
      addition, they appear to have a role in mediating bone formation, since they
      secrete the bone formation inhibitor sclerostin. In contrast to osteoblasts and
      osteoclasts, which reside on the bone surface, it has been difficult to isolate
      and analyze cellular and molecular properties of osteocytes due to their specific
      location inside the "hard" mineralized bone compartment. This chapter describes a
      method to isolate osteocytes from newborn mouse calvaria and adult mouse long
      bone, followed by immediate total RNA extraction allowing to selectively study
      osteocytic versus osteoblastic gene expression by quantitative real-time
      polymerase chain reaction (qPCR). The osteocyte-enriched cell fraction isolated
      by this method can further be purified by FACS and selectively expresses
      osteocytic marker genes, such as Dmp1 and Sost.

PMID- 22130923
TI  - Studying osteocyte function using the cell lines MLO-Y4 and MLO-A5.
AB  - We describe the culture and use of MLO-Y4 cells in studies of gene expression,
      response to fluid flow, and dendrite growth. We also describe how to use the MLO
      A5 cells as a model of osteoblast to osteocyte -differentiation and how to study
      their mineralization. These studies serve as a beginning point to study osteocyte
      functions and molecular mechanisms responsible for these functions.

PMID- 22130924
TI  - Isolation, differentiation, and characterisation of skeletal stem cells from
      human bone marrow in vitro and in vivo.
AB  - In this chapter, we describe techniques for the isolation and characterization of
      skeletal stem cells from human bone marrow. The methods for enrichment of STRO-1
      positive cells using magnetic activated cell sorting are described and we also
      cover techniques for establishing and characterising osteogenic, adipogenic, and
      chondrogenic cultures from these cells. Finally, we present methods for studying
      the ability of these cells to produce bone in vivo using diffusion chambers which
      have been implanted subcutaneously in mice.

PMID- 22130925
TI  - Rodent osteoclast cultures.
AB  - This chapter describes quantitative methods for isolating and culturing rodent
      osteoclasts on dentine, a bone-like, resorbable substrate. These techniques
      generate relatively large numbers of osteoclasts and allow the key processes of
      osteoclast formation and activation to be studied independently. A special focus
      will be on the role of extracellular pH, a critical factor in the control of
      osteoclast function.

PMID- 22130926
TI  - Isolation and culture of primary chicken osteoclasts.
AB  - Osteoclasts originate from hematopoietic myeloid progenitors that differentiate
      into specialized multinucleated cells uniquely capable of resorbing bone in both
      physiological and pathological conditions. Osteoclast numbers and degradative
      activities increase in various inflammatory disorders of bone and certain bone
      oncologies, thereby causing bone loss that may weaken the skeleton, increase
      fracture incidence, and disturb marrow function. Many valuable insights have been
      obtained through the use of osteoclasts directly isolated from the bones of
      chickens fed a low calcium diet to enhance osteoclastogenesis and bone
      resorption. Particular advantages of this system include the abundance and highly
      resorptive nature of isolated chicken osteoclasts compared with those directly
      obtained from other species. After enzymatic release from the harvested bones,
      osteoclasts may be partially purified by density gradient sedimentation, bone
      substrate attachment, and/or immunomagnetic capture. Thereafter, osteoclast
      preparations may be analyzed, either directly or following some period of
      culture, to investigate their properties (biochemical, immunological, molecular,
      cell biological), resorptive function, and modulatory responses to various
      stimuli. Here, we present common procedures for the isolation, culture, and
      general study of chicken osteoclasts.

PMID- 22130927
TI  - Isolation and purification of rabbit osteoclasts.
AB  - Newborn rabbits provide a useful and readily available source of authentic mature
      osteoclasts, which can be easily isolated directly from the long bones in
      relatively large numbers, compared to other rodents. Primary cultures of
      authentic rabbit osteoclasts on resorbable substrates in vitro are an ideal model
      of osteoclast behaviour in vivo, and for some studies may be preferable to
      osteoclast-like cells generated in vitro from bone marrow cultures or from human
      peripheral blood, for example in assessing osteoclast-mediated bone resorption
      independently of effects on osteoclast formation. Rabbits also provide a
      particularly useful model for determining the effects of pharmacological agents
      on osteoclasts in vivo, by isolating osteoclasts using immunomagnetic bead
      separation (with an antibody to alpha(V)beta(3)) at the desired time following in
      vivo administration of the drug. Since osteoclasts are abundant in newborn
      rabbits, sufficient numbers of osteoclasts can be retrieved using this method for
      molecular and biochemical analyses.

PMID- 22130928
TI  - Generation of human osteoclasts from peripheral blood.
AB  - Osteoclasts are multi-nucleated cells that have the unique ability to resorb
      calcified bone matrix. They derive from haematopoietic precursor cells, and can
      be generated in vitro by stimulation of peripheral blood mononuclear cells with
      the cytokines M-CSF and RANKL. In this chapter, we describe the method for
      generating human osteoclast from peripheral blood or buffy coats, as well as
      methods for studying both the differentiation and resorbing activity of these
      cells.

PMID- 22130929
TI  - Osteoclast formation in mouse co-cultures.
AB  - The murine co-culture assay is used to generate mature osteoclasts from bone
      marrow precursors by culturing them with osteoblasts that are stimulated with
      1,25-dihydroxy vitamin D(3) and prostaglandin E(2). This assay is used
      particularly to analyse osteoblast-osteoclast interactions and to determine the
      cell type affected in knock-out or transgenic mice. This chapter describes also
      the isolation of bone marrow cells from mice and the methods to purify and
      replate mature osteoclasts.

PMID- 22130930
TI  - RANKL-mediated osteoclast formation from murine RAW 264.7 cells.
AB  - Extensive research efforts over the years have provided us with great insights
      into how bone-resorbing osteoclasts (OCs) develop and function and, based on such
      work, valuable antiresorptive therapies have been developed to help combat the
      excessive bone loss that occurs in numerous skeletal disorders. The RAW 264.7
      murine cell line has proven to be an important tool for in vitro studies of OC
      formation and function, having particular advantages over the use of OCs
      generated from primary bone marrow cell populations or directly isolated from
      murine bones. These include their ready access and availability, simple culture
      for this pure macrophage/pre-OC population, sensitive and rapid development into
      highly bone-resorptive OCs expressing hallmark OC characteristics following their
      RANKL stimulation, abundance of RAW cell-derived OCs that can be generated to
      provide large amounts of study material, relative ease of transfection for
      genetic and regulatory manipulation, and close correlation in characteristics,
      gene expression, signaling, and developmental or functional processes between RAW
      cell-derived OCs and OCs either directly isolated from murine bones or formed in
      vitro from primary bone marrow precursor cells. Here, we describe methods for the
      culture and RANKL-mediated differentiation of RAW cells into bone-resorptive OCs
      as well as procedures for their enrichment, characterization, and general use in
      diverse analytical assays.

PMID- 22130931
TI  - Transfection of osteoclasts and osteoclast precursors.
AB  - Osteoclasts and their precursors have traditionally been considered difficult
      cells to transfect using standard approaches. Here, we describe several methods
      for transfection of mature osteoclasts and their precursors using the AmaxaTM
      Nucleofector system, lentiviruses, and adenoviruses.

PMID- 22130932
TI  - Analysis of signalling pathways by western blotting and immunoprecipitation.
AB  - This chapter describes the analysis of signalling pathways in bone cells by the
      use of western blotting and immunoprecipitation, including a step by step guide
      to cell culture techniques, protein isolation, purification, measurement,
      electrophoretic transfer, and detection.

PMID- 22130933
TI  - Analysis of transcriptional regulation in bone cells.
AB  - Transcription is the process by which the rate of RNA synthesis is regulated.
      Here, we describe the techniques for carrying out promoter-reporter assays,
      electrophoretic mobility shift assays, and chromatin immunoprecipitation assays,
      three commonly used methods for studying gene transcription.

PMID- 22130934
TI  - Extraction of nucleic acids from bone.
AB  - Here, we present methods for extracting DNA and RNA from samples of whole bone
      tissue and culture bone cells and describe methods quantitative and qualitative
      measurement of the extracted nucleic acids. These protocols described provide
      high-quality nucleic acids suitable for downstream applications such as
      quantitative PCR and microarrays.

PMID- 22130935
TI  - Analysis of gene expression in bone by quantitative RT/PCR.
AB  - This chapter describes methods for quantitation of gene expression in bone cells
      and bone tissues using the technique of quantitative reverse transcription
      polymerase chain reaction.

PMID- 22130936
TI  - Histomorphometry in rodents.
AB  - Bone histomorphometry remains an important tool to study the pathophysiology of
      bone disease and the cellular mechanism by which treatments work. Here, we review
      the methods for embedding, sectioning, staining, and analysis of bone sections in
      rodents.

PMID- 22130937
TI  - Studying gene expression in bone by in situ hybridization.
AB  - Here, we described a method for carrying out nonradioactive in situ hybridization
      to detect mRNA transcripts in cryostat sections of mouse bone using the
      CryoJane((r)) Tape-Transfer System and digoxigenin (DIG)-labeled riboprobes.

PMID- 22130938
TI  - Immunostaining of skeletal tissues.
AB  - Immunohistochemistry (IHC) is a routinely used technique in clinical diagnosis of
      pathological conditions and in basic research. It combines anatomical,
      immunological, and biochemical methods and relies on the specific binding of an
      antibody to an antigen. Using the technique with mineralised tissues is more
      complicated than with soft tissues. This can in most cases be overcome by
      demineralising the samples, which allows embedding in paraffin wax and a simpler
      work-up than for resin-embedded, or for frozen samples. This chapter describes
      methods for IHC on paraffin-embedded formaldehyde fixed sections to detect
      antigens in the musculoskeletal tissues.

PMID- 22130939
TI  - Techniques for the study of apoptosis in bone.
AB  - There has been great interest in the identifying the mechanisms by which
      apoptosis is regulated in bone over recent years and in the biological role that
      this process plays in bone metabolism and bone disease. Here, we describe several
      methods for the detection of apoptosis in bone sections and in bone cell
      cultures.

PMID- 22130940
TI  - Transmission electron microscopy of bone.
AB  - This chapter describes procedures to process mineralized tissues obtained from
      different sources for transmission electron microscopy (TEM). Methods for
      fixation, resin embedding, staining of semi-thin sections and ultrathin sections
      are presented. In addition, attention will be paid to processing of cultured bone
      explants for TEM analysis.

PMID- 22130941
TI  - Scanning electron microscopy of bone.
AB  - This chapter described methods for Scanning Electron Microscopical imaging of
      bone and bone cells. Backscattered electron (BSE) imaging is by far the most
      useful in the bone field, followed by secondary electrons (SE) and the energy
      dispersive X-ray (EDX) analytical modes. This chapter considers preparing and
      imaging samples of unembedded bone having 3D detail in a 3D surface, topography
      free, polished or micromilled, resin-embedded block surfaces, and resin casts of
      space in bone matrix. The chapter considers methods for fixation, drying, looking
      at undersides of bone cells, and coating. Maceration with alkaline bacterial
      pronase, hypochlorite, hydrogen peroxide, and sodium or potassium hydroxide to
      remove cells and unmineralised matrix is described in detail. Attention is given
      especially to methods for 3D BSE SEM imaging of bone samples and recommendations
      for the types of resin embedding of bone for BSE imaging are given. Correlated
      confocal and SEM imaging of PMMA-embedded bone requires the use of glycerol to
      coverslip. Cathodoluminescence (CL) mode SEM imaging is an alternative for
      visualising fluorescent mineralising front labels such as calcein and
      tetracyclines. Making spatial casts from PMMA or other resin embedded samples is
      an important use of this material. Correlation with other imaging means,
      including microradiography and microtomography is important. Shipping wet bone
      samples between labs is best done in glycerol. Environmental SEM (ESEM,
      controlled vacuum mode) is valuable in eliminating -"charging" problems which are
      common with complex, cancellous bone samples.

PMID- 22130942
TI  - Fluorescence imaging of osteoclasts using confocal microscopy.
AB  - In order to understand osteoclast cell biology, it is necessary to culture these
      cells on a physiological -substrate that they can resorb in vitro, such as bone
      or dentine. However, this creates problems for analysis by fluorescence
      microscopy, due to the depth of the sample under investigation. By virtue of its
      optical sectioning capabilities, confocal microscopy is ideal for analysis of
      such samples, enabling precise intracellular localisation of proteins in
      resorbing osteoclasts to be determined. Moreover, by taking a series of images in
      the axial dimension, it is possible to create axial section views and to
      reconstruct 3D images of the osteoclasts, enabling the spatial organisation of
      the structures of interest to be more easily discerned.

PMID- 22130943
TI  - Live imaging of bone cell and organ cultures.
AB  - Over the past two decades there have been unprecedented advances in the
      capabilities for live cell imaging using light and confocal microscopy. Together
      with the discovery of green fluorescent protein and its derivatives and the
      development of a vast array of fluorescent imaging probes and conjugates, it is
      now possible to image virtually any intracellular or extracellular protein or
      structure. Traditional static imaging of fixed bone cells and tissues takes a
      snapshot view of events at a specific time point, but can often miss the dynamic
      aspects of the events being investigated. This chapter provides an overview of
      the application of live cell imaging approaches for the study of bone cells and
      bone organ cultures. Rather than emphasizing technical aspects of the imaging
      equipment, we have focused on what we consider to be the important principles
      that are of most practical use for an investigator setting up these techniques in
      their own laboratory, together with detailed protocols that our laboratory has
      used for live imaging of bone cell and organ cultures.

PMID- 22130944
TI  - Analysis of bone architecture in rodents using microcomputed tomography.
AB  - This chapter describes the use of microcomputed tomography scanning for analysing
      bone structure, focussing on rodent bone. It also discusses sample preparation,
      the correct set-up of the scanner, and the impact of some of the important
      scanner settings.

PMID- 22130945
TI  - Bone measurements by peripheral quantitative computed tomography in rodents.
AB  - This chapter provides information for the use of peripheral quantitative computed
      tomography in small animals, including suggestions for study design, instrument
      setting, and data interpretation.

PMID- 22130946
TI  - Quantitative X-ray imaging of rodent bone by Faxitron.
AB  - This chapter describes the use of digital micro-radiography with the Faxitron
      machine as a means of imaging and quantitating bone mineral content in mice and
      rats.

PMID- 22130947
TI  - Bioluminescence imaging of bone metastasis in rodents.
AB  - Optical imaging is a valuable technique for visualizing and quantifying
      biological processes in living -organisms. Optical imaging can be divided into
      two main imaging modalities: bioluminescence imaging and fluorescence imaging.
      This chapter describes the use of these imaging techniques to image tumour cells
      in mouse models of cancer and to detect early bone metastasis.

PMID- 22130948
TI  - Fourier transform infrared imaging of bone.
AB  - Fourier transform infrared imaging (FTIRI) is a technique that can be used to
      analyze the material properties of bone using tissue sections. In this chapter I
      describe the basic principles of FTIR and the methods for capturing and analyzing
      FTIR images in bone sections.

PMID- 22130949
TI  - Raman microscopy of bone.
AB  - Raman microscopy is a non-destructive technique requiring minimal sample
      preparation that can be used to measure the chemical properties of the mineral
      and collagen parts of bone simultaneously. Modern Raman instruments contain the
      necessary components and software to acquire the standard information required in
      most bone studies. The spatial resolution of the technique is about a micron. As
      it is non-destructive and small samples can be used, it forms a useful part of a
      bone characterisation toolbox.

PMID- 22130950
TI  - The calvarial injection assay.
AB  - This chapter describes the calvarial injection method, whereby the effect of a
      substance on bone is tested by subcutaneous injection over the calvarium of a
      mouse. This assay allows testing of the effect of substances on both bone
      resorption and bone formation in a relatively simple in vivo model. The analysis
      is carried out by histological means, usually in glycolmethacrylate-embedded
      tissue, allowing for histochemical analysis and for a variety of different
      histological staining methods which are also described in detail.

PMID- 22130951
TI  - Ovariectomy/orchidectomy in rodents.
AB  - This chapter describes the surgical procedures for ovariectomy and orchidectomy
      in mice and rats. In -addition to providing technical details of the surgical
      techniques, details of anaesthesia and perioperative care are also included.

PMID- 22130952
TI  - Mechanical properties of bone ex vivo.
AB  - The primary functions of bone are to do with support and protection - mechanical
      functions. The aim of this chapter is to set out some of the methods that can be
      used to measure these properties in cortical and cancelleous bone from large
      (e.g. human or bovine) and small (e.g. mouse) animals. The difference between
      properties of the sample (intrinsic properties) and properties of the material
      (extrinsic properties) is introduced and techniques for measuring them suggested.
      The addition of other tests to give a complete characterisation of a bone sample
      is presented.

PMID- 22130953
TI  - Mechanical stimulation of bone cells using fluid flow.
AB  - This chapter describes several methods suitable for mechanically stimulating
      monolayers of bone cells by fluid shear stress (FSS) in vitro. Fluid flow is
      generated by pumping culture medium through two parallel plates, one of which
      contains a monolayer of cells. Methods for measuring nitric oxide production by
      bone cells in response to FSS are also described.

PMID- 22130954
TI  - Using cell and organ culture models to analyze responses of bone cells to
      mechanical stimulation.
AB  - Bone cells of the osteoblastic lineage are responsive to the local mechanical
      environment. Through integration of a number of possible loading-induced
      regulatory stimuli, osteocyte, osteoblast, and osteoclast behaviour is organized
      to fashion a skeletal element of sufficient strength and toughness to resist
      fracture and crack propagation. Early pre-osteogenic responses had been
      determined in vivo and this led to the development of bone organ culture models
      to elucidate other pre-osteogenic responses where osteocytes and osteoblasts
      retain the natural orientation, connections and attachments to their native
      extracellular matrix. The application of physiological mechanical loads to bone
      in these organ culture models generates the regulatory stimuli. As a consequence,
      these experiments can be used to illustrate the distinctive mechanisms by which
      osteocytes and osteoblasts respond to mechanical loads and also differences in
      these responses, suggesting co-ordinated and cooperatively between cell
      populations. Organ explant cultures are awkward to maintain, and have a limited
      life, but length of culture times are improving. Monolayer cultures are much
      easier to maintain and permit the application of a particular mechanical
      stimulation to be studied in isolation; mainly direct mechanical strain or fluid
      shear strains. These allow for the response of a single cell type to the applied
      mechanical stimulation to be monitored precisely.The techniques that can be used
      to apply mechanical strain to bone and bone cells have not advanced greatly since
      the first edition. The output from such experiments has, however, increased
      substantially and their importance is now more broadly accepted. This suggests a
      growing use of these approaches and an increasing awareness of the importance of
      the mechanical environment in controlling normal bone cell behaviour. We expand
      the text to include additions and modifications made to the straining apparatus
      and update the research cited to support this growing role of cell and organ
      culture models to analyze responses of bone cells to mechanical stimulation.

PMID- 22130955
TI  - In vivo mechanical loading.
AB  - The skeleton fulfils its mechanical functions through structural organisation and
      material properties of individual bones. Both cortical and trabecular morphology
      and mass can be (re)modelled in response to changes in mechanical strains
      engendered by load-bearing. To address this, animal models that enable the
      application of specific loads to individual bones have been developed. These are
      useful in defining how loading modulates (re)modelling and allow examination of
      the mechanisms that coordinate these events. This chapter describes how to apply
      mechanical loading to murine bones through points of articulation, which allows
      changes in endosteal, periosteal as well as trabecular bone to be revealed by
      double fluorochrome labelling and computed tomography, respectively.

PMID- 22130958
TI  - Association of serum calcitonin with coronary artery disease in individuals with
      and without chronic kidney disease.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death in patients with
      chronic kidney disease (CKD). Recent data implicate disordered bone and mineral
      metabolism, including changes in serum levels of calcium, phosphate, parathyroid
      hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and fetuin A, as
      novel risk factors for arterial calcification. The potential role of calcitonin,
      another hormonal regulator of mineral and bone metabolism, has not been studied
      in detail. MATERIALS AND METHODS: We investigated the link between serum
      calcitonin and the total burden of coronary artery disease (CAD) using the
      validated Gensini score, in a cross-sectional study of 88 patients with estimated
      GFR (eGFR) between 46 and 87 ml/min/1.73 m2 who underwent coronary angiography.
      We evaluated the associations between serum calcitonin, minerals (calcium,
      phosphate), calcium * phosphate product, and other factors that regulate mineral
      metabolism (intact PTH, 25-OH-vitamin D, FGF-23, and fetuin A) and the severity
      of CAD. RESULTS: The mean serum calcitonin was 11.5 +/- 7.8 pg/ml. In univariate
      analysis, the Gensini CAD severity score correlated significantly with male
      gender, eGFR, and serum levels of 25-OH-vitamin D, iPTH, FGF-23, fetuin A, and
      calcitonin (R = 0.474, P = 0.001 for the latter). In multivariate analysis
      adjusted for calcium, phosphate, 25-OH-vitamin D, iPTH, FGF 23, fetuin A, and
      calcitonin, only calcitonin (beta = 0.20; P = 0.03), FGF-23, fetuin A, and 25-OH
      vitamin D emerged as independent predictors of Gensini score. In the second step,
      we adjusted for the presence of traditional risk factors, proteinuria, and GFR.
      After these adjustments, the FGF-23 and fetuin A remained statistically
      significant predictors of the Gensini score, while calcitonin did not.
      CONCLUSIONS: Our study suggests that, in addition to other well-known components
      of mineral metabolism, increased calcitonin levels are associated with greater
      severity of CAD. However, this relation was not independent of traditional and
      nontraditional cardiovascular risk factors. Longitudinal studies in larger
      populations including patients with more advanced CKD are needed.

PMID- 22130959
TI  - Is hemojuvelin a possible new player in iron metabolism in hemodialysis patients?
AB  - INTRODUCTION: Hemojuvelin (HJV) is highly expressed in the liver, skeletal
      muscles, and heart, seems to play a role in iron absorption and release from
      cells, and has anti-inflammatory properties. Moreover, HJV plays an essential
      role in the regulation of hepcidin expression, specifically in the iron-sensing
      pathway. Hepcidin has emerged as a key regulator of iron homeostasis. In this
      study we tested for the first time the hypothesis that HJV is related to iron
      metabolism in hemodialysis (HD) patients. METHODS: Iron status, complete blood
      count, and serum creatinine, albumin, and lipids were assessed, using standard
      laboratory methods. Serum levels of soluble transferrin receptor (sTFR), high
      sensitivity CRP, IL-6, hepcidin, and HJV were measured using commercially
      available kits. RESULTS: Serum HJV, hepcidin, ferritin, IL-6, hsCRP, and serum
      creatinine were significantly higher (all P<0.001), whereas serum iron, sTFR,
      transferrin, hemoglobin, and erythrocyte count were significantly lower in HD
      patients, compared to healthy volunteers (all P<0.001). In univariate analysis,
      HJV was strongly correlated (P<0.001) with ferritin, transferrin saturation, and
      TIBC, as well as with hsCRP, hepcidin, Kt/V (P<0.01) and residual renal function,
      the presence of diabetes, APKD, and coronary heart disease. Predictors of HJV
      level in multiple regression analysis were ferritin (beta value was 0.50,
      P=0.00004) and transferrin saturation (beta value was 0.47, P=0.0002), explaining
      81% of the HJV variations. CONCLUSIONS: Serum HJV is elevated in HD patients and
      related predominantly to kidney function and iron metabolism. However, HJV is
      probably not correlated to inflammation. HJV appears to be a new player in iron
      metabolism in these patients.

PMID- 22130960
TI  - Long-term safety, tolerability, and efficacy of alpha1-adrenergic blocker in
      young men with primary bladder neck obstruction: results from a single centre in
      China.
AB  - OBJECTIVE: Primary bladder neck obstruction (PBNO) is a nonneurogenic voiding
      disorder and frequently overlooked in young men. Prior studies have reported the
      efficacy of alpha-blockers only in the short-term for male patients with PBNO. We
      hereby report our long-term results using alpha1-blocker therapy in young men
      with PBNO. METHODS: Between January 2005 and December 2009, PBNO was diagnosed in
      30 young men (mean age 27.3 years, range 18-35) at our institution. Doxazosin 4
      mg once daily was administered for at least 12 months. Safety and tolerability
      were assessed, and efficacy was evaluated from International Prostate Symptom
      Score (I-PSS), Quality of Life (QOL), uroflowmetry, and post-void residual
      following 3- and 12-month treatment. Successful treatment was defined as at least
      3 ml per second increase in the maximum flow rate and more than a 40% decrease in
      I-PSS. RESULTS: In all 30 patients, Mean symptom duration was 26.4 (3-65) months.
      The most common symptoms were hesitancy (93.3%), weak stream (76.7%), and
      frequency (66.7%). A total of 24 patients (80%, 24/30) successfully completed the
      12 month of treatment. The medication period was 15.2 months, and follow-up
      duration was 16.3 months. Doxazosin was safe and well tolerated. The efficacy of
      doxazosin was maintained over the 12-month treatment period. Relative to
      baseline, there were reductions in the number of mean I-PSS (from 17.7 +/- 4.2 to
      10.4 +/- 4.8), mean QOL (from 4.2 +/- 1.1 to 2.4 +/- 1.3), and mean post-void
      residual urine (from 79.3 +/- 33.4 to 47.1 +/- 21.3), and an increase in mean
      maximum flow rate (from 11.4 +/- 2.9 to 15.1 +/- 3.2 ml) after 12-month
      treatment. Treatment was successful in 16 patients (66.7%, 16/24) according to
      the improvement in both symptoms and maximum urine flow. CONCLUSIONS: alpha1
      blocker therapy displayed a favorable safety, tolerability, and efficacy profile
      during 12-month treatment in young male patients with PBNO.

PMID- 22130961
TI  - The induction of apoptosis by Shiga toxins and ricin.
AB  - Shiga toxins and ricin are ribosome-inactivating proteins which share the
      property of inhibiting protein synthesis by catalytic inactivation of eukaryotic
      ribosomes. There is now abundant evidence that Shiga toxins and ricin induce
      apoptosis in epithelial, endothelial, lymphoid and myeloid cells in vitro, and in
      multiple organs in animals when administered these toxins. Many studies suggest
      that protein synthesis inhibition and apoptosis induction mediated by Shiga
      toxins and ricin may be dissociated. In some cells, non-enzymatic toxin
      components (Shiga toxin B-subunits, ricin B-chain) appear capable of inducing
      apoptosis. The toxins appear capable of activating components of both the
      extrinsic or death receptor-mediated and intrinsic or mitochondrial-mediated
      pathways of apoptosis induction. Although the toxins have been shown to be
      capable of activating several cell stress response pathways, the precise
      signaling mechanisms by which Shiga toxins and ricin induce apoptosis remain to
      be fully characterized. This chapter provides an overview of studies describing
      Shiga toxin- and ricin-induced apoptosis and reviews evidence that signaling
      through the ribotoxic stress response and the unfolded protein response may be
      involved in apoptosis induction in some cell types.

PMID- 22130962
TI  - Impact of the SRC inhibitor dasatinib on the metastatic phenotype of human
      prostate cancer cells.
AB  - SRC, a non-receptor tyrosine kinase, is frequently over-expressed and highly
      activated in blood as well as solid tumors in various organs, including prostate,
      and has been associated with aggressive disease and a poor patient prognosis.
      Prostate cancer patients with a high risk of developing metastases have few
      treatment options, none of which can result in a durable cure. Therefore, the aim
      of the present study was to examine the impact of a SRC inhibitor, dasatinib, on
      the ability of human prostate cancer cell to complete key steps in the metastatic
      process, including invasion and angiogenesis. Dasatinib treatment impaired the
      metastatic phenotypes of the human prostate cancer cell lines, PC-3, DU-145, and
      LNCaP, by significantly reducing migration and invasion in modified Boyden
      chambers. Inhibition of phosphorylation, and therefore enhanced activation, of
      SRC and key downstream signaling pathway elements, including FAK, STAT3,
      Paxillin, and Akt, as determined by Western blotting, also was observed. This
      suggests that dasatinib interferes with critical cell functions associated with
      the metastatic cascade. Dasatinib also had direct effects on the ability of
      microvascular endothelial cells to form tubes in vitro and impaired the ability
      of PC-3 cells to induce angiogenesis in vivo. In conclusion, the present findings
      suggest that SRC inhibition by dasatinib may have utility in reducing the
      metastatic spread of prostate cancer cells.

PMID- 22130963
TI  - Alteration of bone sialoprotein expression in osseous metastasized renal cell
      carcinomas and the tumor surrounding tissue.
AB  - Bone sialoprotein (BSP) regulates bone metabolism by directly influencing the
      activity of osteoblasts and osteoclasts. A significant correlation between the
      tissue expression of BSP in tumors and the occurrence of bone metastases was
      found in different cancers. Aim of this study was to identify the BSP expression
      in renal cell carcinomas (RCC) according to their stage of metastatic disease.
      Tissue samples of patients with RCC who underwent partial resection or
      nephrectomy were separated into three groups, each with 10 patients showing
      either no metastases (group I), only soft tissue metastases (group II) or bone
      metastases (group III) at date of surgery. Immunohistochemical analysis of BSP
      expression in tumor tissue and corresponding renal parenchyma was performed and
      evaluated with an established semiquantitative scoring system. BSP expression was
      detected both in tumor tissue and renal parenchyma. Concerning the expression in
      malignant tissue, no significant difference could be found between the three
      groups whereas the corresponding renal parenchyma showed a staining score of 164,
      198 and 224 for group I, II and III (P = 0.07). RCC staged T3 showed only a
      little higher BSP expression than those staged T1/2 (P < 0.21), while the
      corresponding parenchyma of T3 tumors showed significantly higher expressions (P
      = 0.02). This pilot study revealed a correlation between expression of BSP and
      tumor staging and type of metastases, especially for osseous metastases in RCC.
      Alternation of BSP expression could be detected particularly in renal parenchyma
      and linked to the type of metastases.

PMID- 22130964
TI  - Selective adenosine agonists and myocardial perfusion imaging.
AB  - Selective adenosine receptor agonists have several advantages for use as stress
      agents in conjunction with myocardial perfusion imaging compared to the non
      selective agents such as adenosine and dipyridamole. This review will summarize
      the pre-clinical and clinical data on the selective adenosine agonist stress
      agents regadenoson (Lexiscan((r))), binodenoson (CorVueTM) and apadenoson
      (StedivazeTM) that have been studied so far with focus on regadenoson that has
      the most clinical data published so far. The article will review the adenosine
      receptor types and properties. It will also review the various attributes of the
      selective adenosine agonists including their pharmacology, pharmacokinetics and
      pharmacodynamics, their coronary vasodilatory and hemodynamic effects, their
      safety and side effects, their interactions with other drugs and their use with
      myocardial perfusion imaging. The landmark trials of the selective adenosine
      agonists will be reviewed as well as their use in special patient populations
      undergoing stress myocardial perfusion imaging.

PMID- 22130966
TI  - Does location matter? Prognostic value of single-photon emission computed
      tomography myocardial perfusion imaging by vascular territory.
AB  - BACKGROUND: The location of a myocardial perfusion abnormality frequently affects
      clinical decision making, especially if the left anterior descending artery (LAD)
      territory is involved. The purpose of this study was to determine whether the
      location of abnormalities on single-photon emission computed tomography (SPECT)
      imaging affects outcomes. METHODS: We retrospectively analyzed 21,294 consecutive
      patients with known or suspected coronary artery disease who underwent exercise
      or pharmacological stress SPECT over a 10-year period. Using the ASNC 17-segment
      model, 2 observers interpreted images with regards to defect severity, size, and
      reversibility. The summed stress score (SSS) was used in relation to vascular
      territories [LAD, right coronary artery (RCA), and left circumflex artery (LCx)].
      All patients were followed over a mean period of 2.5 +/- 2 years for cardiac
      events (cardiac death or non-fatal myocardial infarction). RESULTS: Of the
      enrolled patients, 5,676 had single-vessel territory defects with a mean SSS of
      4.3 +/- 2.8. Cardiac event-free survival curves revealed no significant
      difference between the 3 locations (LAD, RCA, and LCx) (P = .235). When compared
      by mild (2-3), moderate (4-8), or severe (>8) SSS, outcomes between the 3 groups
      were again similar. There were 2,907 patients with two-vessel territory defects
      with a mean SSS of 10.8. Outcomes were similar between the following 2 groups:
      two-vessel with LAD involvement and two-vessel without LAD involvement (P =
      .558). CONCLUSION: In patients with single- or two-vessel territory perfusion
      abnormalities with similar size and severity of perfusion defects, the location
      of defect did not impact future cardiac events. Location of myocardial perfusion
      defect on SPECT imaging may not be helpful in clinical decision making.

PMID- 22130965
TI  - Use of cardiac radionuclide imaging to identify patients at risk for arrhythmic
      sudden cardiac death.
AB  - Sudden cardiac death (SCD) accounts for about 1/2 of all cardiovascular deaths,
      in most cases the result of a lethal ventricular arrhythmia. Patients considered
      at risk are often treated with an implantable cardiac defibrillator (ICD), but
      current criteria for device use, based largely on left ventricular ejection
      fraction (LVEF), leads to many patients receiving ICDs that they do not use, and
      many others not receiving ICDs but who suffer SCD. Thus, better methods of
      identifying patients at risk for SCD are needed, and radionuclide imaging offers
      much potential. Recent work has focused on imaging of cardiac autonomic
      innervation. (123)I-mIBG, a norepinephrine analog, is the tracer most studied,
      and a variety of positron emission tomographic tracers are also under
      investigation. Radionuclide autonomic imaging may identify at-risk patients with
      ischemic coronary artery disease, particularly following myocardial infarction
      and in the setting of hibernating myocardium. Most studies have been done in the
      setting of congestive heart failure (CHF), with a recent large multicenter study
      of patients with advanced disease, typically at high risk of SCD, showing that
      (123)I-mIBG can identify a low risk subgroup with an extremely low incidence of
      lethal ventricular arrhythmias and cardiac death, therefore, perhaps not
      requiring an ICD. Cardiac neuronal imaging has been shown to be better predictive
      of lethal arrhythmias/cardiac death than LVEF and New York Heart Association
      class, as well as various ECG parameters. Autonomic imaging will likely play an
      important role in the advancement of cardiac molecular imaging.

PMID- 22130967
TI  - Fast and efficient MCR-based synthesis of clickable rhodamine tags for protein
      profiling.
AB  - Protein profiling probes are important tools for studying the composition of the
      proteome and as such have contributed greatly to the understanding of various
      complex biological processes in higher organisms. For this purpose the
      application of fluorescently labeled activity or affinity probes is highly
      desirable. Especially for in vivo detection of low abundant target proteins,
      otherwise difficult to analyse by standard blotting techniques, fluorescently
      labeled profiling probes are of high value. Here, a one-pot protocol for the
      synthesis of activated fluorescent labels (i.e. azide, alkynyl or NHS), based on
      the Ugi-4-component reaction (Ugi-4CR), is presented. As a result of the
      peptoidic structure formed, the fluorescent properties of the products are pH
      insensitive. Moreover, the applicability of these probes, as exemplified by the
      labeling of model protein BSA, will be discussed.

PMID- 22130968
TI  - Large-scale analysis of plasmid relationships through gene-sharing networks.
AB  - Plasmids are vessels of genetic exchange in microbial communities. They are known
      to transfer between different host organisms and acquire diverse genetic elements
      from chromosomes and/or other plasmids. Therefore, they constitute an important
      element in microbial evolution by rapidly disseminating various genetic
      properties among different communities. A paradigmatic example of this is the
      dissemination of antibiotic resistance (AR) genes that has resulted in the
      emergence of multiresistant pathogenic bacterial strains. To globally analyze the
      evolutionary dynamics of plasmids, we built a large graph in which 2,343 plasmids
      (nodes) are connected according to the proteins shared by each other. The
      analysis of this gene-sharing network revealed an overall coherence between
      network clustering and the phylogenetic classes of the corresponding
      microorganisms, likely resulting from genetic barriers to horizontal gene
      transfer between distant phylogenetic groups. Habitat was not a crucial factor in
      clustering as plasmids from organisms inhabiting different environments were
      often found embedded in the same cluster. Analyses of network metrics revealed a
      statistically significant correlation between plasmid mobility and their
      centrality within the network, providing support to the observation that mobile
      plasmids are particularly important in spreading genes in microbial communities.
      Finally, our study reveals an extensive (and previously undescribed) sharing of
      AR genes between Actinobacteria and Gammaproteobacteria, suggesting that the
      former might represent an important reservoir of AR genes for the latter.

PMID- 22130969
TI  - Evolution of functionally diverse alleles associated with PTC bitter taste
      sensitivity in Africa.
AB  - Although human bitter taste perception is hypothesized to be a dietary
      adaptation, little is known about genetic signatures of selection and patterns of
      bitter taste perception variability in ethnically diverse populations with
      different diets, particularly from Africa. To better understand the genetic basis
      and evolutionary history of bitter taste sensitivity, we sequenced a 2,975 bp
      region encompassing TAS2R38, a bitter taste receptor gene, in 611 Africans from
      57 populations in West Central and East Africa with diverse subsistence patterns,
      as well as in a comparative sample of 132 non-Africans. We also examined the
      association between genetic variability at this locus and threshold levels of
      phenylthiocarbamide (PTC) bitterness in 463 Africans from the above populations
      to determine how variation influences bitter taste perception. Here, we report
      striking patterns of variation at TAS2R38, including a significant excess of
      novel rare nonsynonymous polymorphisms that recently arose only in Africa, high
      frequencies of haplotypes in Africa associated with intermediate bitter taste
      sensitivity, a remarkably similar frequency of common haplotypes across
      genetically and culturally distinct Africans, and an ancient coalescence time of
      common variation in global populations. Additionally, several of the rare
      nonsynonymous substitutions significantly modified levels of PTC bitter taste
      sensitivity in diverse Africans. While ancient balancing selection likely
      maintained common haplotype variation across global populations, we suggest that
      recent selection pressures may have also resulted in the unusually high level of
      rare nonsynonymous variants in Africa, implying a complex model of selection at
      the TAS2R38 locus in African populations. Furthermore, the distribution of common
      haplotypes in Africa is not correlated with diet, raising the possibility that
      common variation may be under selection due to their role in nondietary
      biological processes. In addition, our data indicate that novel rare mutations
      contribute to the phenotypic variance of PTC sensitivity, illustrating the
      influence of rare variation on a common trait, as well as the relatively recent
      evolution of functionally diverse alleles at this locus.

PMID- 22130970
TI  - High resolution mapping of candidate alleles for desiccation resistance in
      Drosophila melanogaster under selection.
AB  - The ability to counter periods of low humidity is an important determinant of
      distribution range in Drosophila. Climate specialists with low physiological
      tolerance to desiccation stress are restricted to the tropics and may lack the
      ability to further increase resistance through evolution. Although the
      physiological adaptations to desiccation stress are well studied in Drosophila
      and other ectotherms, factors underlying evolutionary responses remain unknown
      because of a paucity of genetic data. We address this issue by mapping
      evolutionary shifts in D. melanogaster under selection for desiccation
      resistance. Genomic DNA from five independent replicate selected, and control
      lines were hybridized to high density Affymetrix Drosophila tiling arrays
      resulting in the detection of 691 single feature polymorphisms (SFPs) differing
      between the treatments. While randomly distributed throughout the genome, the
      SFPs formed specific clusters according to gene ontology. These included genes
      involved in ion transport and respiratory system development that provide
      candidates for evolutionary changes involving excretory and respiratory water
      balance. Changes to genes related to neuronal control of cell signaling,
      development, and gene regulation provide candidates to explore novel biological
      processes in stress resistance. Sequencing revealed the nucleotide shifts in a
      subset of the SFPs and highlighted larger regions of genomic diversity
      surrounding SFPs. The association between natural desiccation resistance and a
      463-bp region of the 5' promoter region of the Dys gene undergoing allele
      frequency changes in response to selection in the experimental evolution lines
      was tested in an independent population from Coffs Harbour, Australia. The allele
      frequencies of 23 SNPs common to the two populations were inferred from the
      parents of the 10% most and 10% least resistant Coffs Harbour flies. The
      frequencies of the selected alleles were higher at all sites, with three sites
      significantly associated with the resistant Coffs Harbour flies. This study
      illustrates how rapid mapping can be used for discovering natural molecular
      variants associated with survival to low humidity and provides a wealth of
      candidate alleles to explore the genetic basis of physiological differences among
      resistant and susceptible Drosophila populations and species.

PMID- 22130971
TI  - Deciphering the signature of selective constraints on cancerous mitochondrial
      genome.
AB  - In accordance with the hypothesis that cancer formation is a process of somatic
      evolution driven by natural selection, signature of positive selection has been
      detected on a number of cancer-related nuclear genes. It remains, however,
      controversial whether a similar selective pressure has also acted on
      mitochondrial DNA (mtDNA), a small molecule in mitochondrion that may play an
      important role in tumorigenesis by altering oxidative phosphorylation. To better
      understand the mutational pattern on cancerous mtDNA and decipher the genetic
      signature left by natural selection, a total of 186 entire mitochondrial genomes
      of cancerous and adjacent normal tissues from 93 esophageal cancer patients were
      obtained and extensively studied. Our results revealed that the observed
      mutational pattern on the cancerous mtDNAs might be best explained as relaxation
      of negative selection. Taking into account an additional 1,235 cancerous (nearly)
      complete mtDNA sequences retrieved from the literature, our results suggested
      that the relaxed selective pressure was the most likely explanation for the
      accumulation of mtDNA variation in different types of cancer. This notion is in
      good agreement with the observation that aerobic glycolysis, instead of
      mitochondrial respiration, plays the key role in generating energy in cancer
      cells. Furthermore, our study provided solid evidence demonstrating that problems
      in some of the published cancerous mtDNA data adequately explained the previously
      contradictory conclusions about the selective pressure on cancer mtDNA, thus
      serving as a paradigm emphasizing the importance of data quality in affecting our
      understanding on the role of mtDNA in tumorigenesis.

PMID- 22130972
TI  - Contrasting maternal and paternal histories in the linguistic context of Burkina
      Faso.
AB  - Burkina Faso is located in the heart of West Africa and is a representative of
      the local structured patterns of human variability. Here, different cultures and
      languages are found in a geographic contiguity, as a result of several waves of
      migration and the succession of long- and short-term empires. However, historical
      documentation for this area is only partial, focusing predominantly on the recent
      empires, and linguistic surveys lack the power to fully elucidate the social
      context of the contact-induced changes. In this paper, we report Y-chromosomal
      data and complete mtDNA genome sequences for ten populations from Burkina Faso
      whose languages belong to two very distantly related branches of the Niger-Congo
      phylum, the Gur and Mande language families. In addition, two further
      populations, the Mande-speaking Mandenka from Senegal and the Yoruba from
      Nigeria, were included for regional comparison. We focus on the different
      historical trajectories undergone by the maternal and paternal lineages. Our
      results reveal a striking structure in the paternal line, which matches the
      linguistic affiliation of the ethnolinguistic groups, in contrast to the near
      complete homogeneity of the populations in the maternal line. However, while the
      ancient structure along the linguistic lines is apparent in the Y-chromosomal
      haplogroup affiliation, this has clearly been overlain by more recent migrations,
      as shown by significant correlations between the genetic distances based on Y
      chromosome short tandem repeats and geographic distances between the populations,
      as well as by the patterns of shared haplotypes. Using the complete mtDNA
      sequences, we are able to reconstruct population size variation in the past,
      showing a strong sign of expansion in the concomitance with the Holocene Climate
      Optimum approximately 12,000-10,000 years ago, which has been suggested as the
      cause of the spread of the Niger-Congo phylum in the area. However, subsequent
      climatic fluctuations do not appear to have had an impact on the demography of
      the inhabitants of West Africa, probably reflecting the adaptive advantages of
      cultural innovations, such as pastoralism and agriculture.

PMID- 22130973
TI  - Preclinical evaluation of Mab CC188 for ovarian cancer imaging.
AB  - Cancer stem cells (CSCs) have been successfully isolated from solid tumors and
      are believed to be initiating cells of primary, metastatic and recurrent tumors.
      Imaging and therapeutic reagents targeted to CSCs have potential to detect
      subclinical tumors and completely eradicate the disease. Previously, we have
      demonstrated that Mab CC188 binds to colon cancer CD133- and CD133+ (CSCs) cells.
      In this study, we examined the reactivity of Mab CC188 to ovarian cancer cells
      including CD133+ cells and primary tumor tissues using immunofluorescence
      staining methods and tissue microarray technique. We also explored the
      feasibility of using NIR dye-labeled Mab CC188 probe to image ovarian tumors in
      vivo. Mab CC188 stains both CD133- and CD133+ cells of ovarian cancer. Tissue
      microarray analysis reveals that 75% (92/123) of ovarian cancer cases are
      positively stained with Mab CC188. Weak positive (+/-), positive (+), strong
      positive (++) and very strong positive (+++) stains are 14.8, 3.7, 11 and 24.4%,
      respectively. In contrast, Mab CC188 staining is low in normal cells and tissues.
      In vivo study show that significant amounts of the probe accumulates in the
      excretion organs in the early period postinjection. At 24 hr, the imaging probes
      have largely accumulates in the tumor, while the intensity of the imaging probe
      decreases in the liver. The tumor uptake was still evident at 120-hr
      postinjection. Our work suggests that Mab CC188-based imaging and therapeutic
      reagents are capable of detecting early stage ovarian tumors and effectively
      treating the tumor.

PMID- 22130974
TI  - Avidity maturation of anti-citrullinated protein antibodies in rheumatoid
      arthritis.
AB  - OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) are highly specific for
      rheumatoid arthritis (RA) and are present years before the onset of symptoms. The
      avidity of autoantibodies can have a strong impact on their effector potency.
      This study was undertaken to analyze the avidity of ACPAs in serum samples
      obtained from ACPA-positive healthy individuals (predisease), patients with early
      disease, and patients with established RA as well as the avidity maturation over
      time in samples from healthy subjects who later developed RA. METHODS: We
      measured ACPA avidity in serum samples from ACPA-positive healthy individuals,
      symptomatic individuals, and patients with established RA in 5 collections from
      The Netherlands, Canada, and Austria. We determined the dynamics of avidity
      maturation of ACPAs from the predisease stage to established disease in 1 case
      from the native North American population and in 10 cases from a Dutch blood
      donor cohort. RESULTS: The overall ACPA response was characterized by low-avidity
      antibodies. Higher-avidity ACPAs were observed in symptomatic patients only,
      while low-avidity ACPAs were observed in both healthy subjects and patients. In
      longitudinal samples obtained from subjects prior to disease onset, ACPA avidity
      increased over time until disease onset. No further avidity maturation was
      observed after disease onset. CONCLUSION: Our findings indicate that avidity
      maturation of the ACPA response takes place prior to disease onset.

PMID- 22130975
TI  - Assessment of Chlamydia trachomatis infection among Eastern European and West
      African women immigrants in South Italy.

PMID- 22130976
TI  - Element interactions and soil properties affecting the soil-to-plant transfer of
      six elements relevant to radioactive waste in boreal forest.
AB  - Cobalt (Co), lead (Pb), molybdenum (Mo), nickel (Ni), uranium (U), and zinc (Zn)
      are among the elements that have radioactive isotopes in radioactive waste. Soil
      to-plant transfer is a key process for possible adverse effects if these
      radionuclides are accidentally released into the environment. The present study
      aimed at investigating factors affecting such transfer in boreal forest. The
      plant species studied were blueberry (Vaccinium myrtillus), May lily (Maianthemum
      bifolium), narrow buckler fern (Dryopteris carthusiana), rowan (Sorbus aucuparia)
      and Norway spruce (Picea abies). Regression analyses were carried out to
      investigate the effects of the chemical composition and physical properties of
      soil on the soil-to-leaf/needle concentration ratios of Co, Mo, Ni, Pb, U and Zn.
      Soil potassium (K), magnesium (Mg), manganese (Mn), phosphorus (P) and sulphur
      (S) concentrations were the most important factors affecting the soil-to-plant
      transfer of the elements studied. Soil clay and organic matter contents were
      found to significantly affect plant uptake of Mo, Pb and U. Knowledge of the
      effects of these factors is helpful for interpretation of the predictions of
      radioecological models describing soil-to-plant transfer and for improving such
      models.

PMID- 22130979
TI  - Prediction of protein tertiary structures using MUFOLD.
AB  - There have been steady improvements in protein structure prediction during the
      past two decades. However, current methods are still far from consistently
      predicting structural models accurately with computing power accessible to common
      users. To address this challenge, we developed MUFOLD, a hybrid method of using
      whole and partial template information along with new computational techniques
      for protein tertiary structure prediction. MUFOLD covers both template-based and
      ab initio predictions using the same framework and aims to achieve high accuracy
      and fast computing. Two major novel contributions of MUFOLD are graph-based model
      generation and molecular dynamics ranking (MDR). By formulating a prediction as a
      graph realization problem, we apply an efficient optimization approach of
      Multidimensional Scaling (MDS) to speed up the prediction dramatically. In
      addition, under this framework, we enhance the predictions consistently by
      iteratively using the information from generated models. MDR, in contrast to
      widely used static scoring functions, exploits dynamics properties of structures
      to evaluate their qualities, which can often identify best structures from a pool
      more effectively.

PMID- 22130980
TI  - Prediction of protein functions.
AB  - The recent explosion in the number and diversity of novel proteins identified by
      the large-scale "omics" technologies poses new and important questions to the
      blossoming field of systems biology--what are all these proteins, how did they
      come about, and most importantly, what do they do? From a comparatively small
      number of protein structural domains a staggering array of structural variants
      has evolved, which has in turn facilitated an expanse of functional derivatives.
      This review considers the primary mechanisms that have contributed to the
      vastness of our existing, and expanding, protein repertoires, while also
      outlining the protocols available for elucidating their true biological function.
      The various function prediction programs available, both sequence and structure
      based, are discussed and their associated strengths and weaknesses outlined.

PMID- 22130981
TI  - Genome-wide screens for expressed hypothetical proteins.
AB  - A hypothetical protein (HP) is defined as a protein that is predicted to be
      expressed from an open reading frame, but for which there is no experimental
      evidence of translation. HPs constitute a substantial fraction of proteomes of
      human as well as of other organisms. With the general belief that the majority of
      HPs are the product of pseudogenes, it is essential to have a tool with the
      ability of pinpointing the minority of HPs with a high probability of being
      expressed.

PMID- 22130982
TI  - Self-custom-made SFP arrays for nonmodel organisms.
AB  - Successful genetic mapping is dependent upon a high-density set of markers.
      Therefore, tools for high-throughput discovery of genetic variation are
      essential. The most abundant genetic marker is the single-nucleotide polymorphism
      (SNP). However, except for model organisms, genomic information is still limited.
      Although high-throughput genomic sequencing technologies are becoming relatively
      inexpensive, only low-throughput genetic markers are accessible (e.g., simple
      sequence repeats). The use of sequencing for the discovery and screening of high
      density genetic variation in whole populations is still expensive. Alternatively,
      hybridization of genomic DNA (gDNA) on a reference (either genome or
      transcriptome) is an efficient approach for genetic screening without knowing the
      alleles in advance (Borevitz et al. Proc Natl Acad Sci USA 104:12057-12062). We
      describe a protocol for the design of probes for a high-throughput genetic-marker
      discovery microarray, termed single feature polymorphism (SFP) array. Starting
      with consensus cDNA sequences (UniGenes), we use OligoWiz to design T (m)
      optimized 50-bp long oligonucleotide probes (Ophir et al. BMC Genomics 11:269,
      2010). This design is similar to expression arrays and we point out the
      differences.

PMID- 22130983
TI  - Construction and analysis of full-length and normalized cDNA libraries from
      citrus.
AB  - We have developed an integrated method to generate a normalized cDNA collection
      enriched in full-length and rare transcripts from citrus, using different species
      and multiple tissues and developmental stages. Interpretation of ever-increasing
      raw sequence information generated by modern genome sequencing technologies faces
      multiple challenges, such as gene function analysis and genome annotation. In
      this regard, the availability of full-length cDNA clones facilitates functional
      analysis of the corresponding genes enabling manipulation of their expression and
      the generation of a variety of tagged versions of the native protein. The
      development of full-length cDNA sequences has the power to improve the quality of
      genome annotation, as well as provide tools for functional characterization of
      genes.

PMID- 22130984
TI  - Assembling linear DNA templates for in vitro transcription and translation.
AB  - Cell-free expression systems provide straightforward access from genes to the
      corresponding proteins, involving fewer handling steps than in vivo procedures. A
      quick procedure to assemble a gene of interest into a linear DNA template
      together with 3'- and 5'-untranslated regions using a coupled uracil-excision
      ligation strategy based on USER Enzyme and T4 DNA ligase. This methodology will
      be useful for repeated cycles of expression and in vitro selection, in which gene
      libraries are repeatedly assembled and their products and templates regenerated.

PMID- 22130985
TI  - Automated computational analysis of genome-wide DNA methylation profiling data
      from HELP-tagging assays.
AB  - A novel DNA methylation assay, HELP-tagging, has been recently described to use
      massively parallel sequencing technology for genome-wide methylation profiling.
      Massively parallel sequencing-based assays such as this produce substantial
      amounts of data, which complicate analysis and necessitate the use of significant
      computational resources. To simplify the processing and analysis of HELP-tagging
      data, a bioinformatic analytical pipeline was developed. Quality checks are
      performed on the data at various stages, as they are processed by the pipeline to
      ensure the accuracy of the results. A quantitative methylation score is provided
      for each locus, along with a confidence score based on the amount of information
      available for determining the quantification. HELP-tagging analysis results are
      supplied in standard file formats (BED and WIG) that can be readily examined on
      the UCSC genome browser.

PMID- 22130986
TI  - Detection of RNA editing events in human cells using high-throughput sequencing.
AB  - RNA editing can lead to amino acid substitutions in protein sequences,
      alternative pre-mRNA splicing, and changes in gene expression levels. The exact
      in vivo modes of interaction of the RNA editing enzymes with their targets are
      not well understood. Alterations in RNA editing have been linked to various human
      disorders and the improved understanding of the editing mechanism and specificity
      can explain the phenotypes that result from misregulation of RNA editing.
      Unbiased high-throughput methods of detection of RNA editing events genome-wide
      in human cells are necessary for the task of deciphering the RNA editing
      regulatory code. With the rapidly falling cost of genome resequencing, the future
      method of choice for the detection of RNA editing events will be whole-genome
      gDNA and cDNA sequencing. We describe a detailed procedure for the computational
      identification of RNA editing targets using the data from the deep sequencing of
      DNA and RNA from the peripheral blood mononuclear cells of a human individual
      with severe hemophilia A who is resistant to HIV infection. Interestingly, we
      find that mRNAs of the cyclin-dependent kinase CDK13 and the DNA repair enzyme
      NEIL1 undergo extensive A -> I RNA editing that leads to amino acid substitutions
      in protein sequences.

PMID- 22130987
TI  - Comparative study of differential gene expression in closely related bacterial
      species by comparative hybridization.
AB  - The ability to profile bacterial gene expression has markedly advanced the
      capacity to understand the molecular mechanisms of pathogenesis, epidemiology,
      and therapeutics. This advance has been coupled with the development of
      techniques that enable investigators to identify bacterial specifically expressed
      genes and promise to open new avenues of functional genomics by allowing
      researchers to focus on the identified differentially expressed genes. During the
      past two decades, a number of approaches have been developed to investigate
      bacterial genes differentially expressed in response to the changing environment,
      particularly during interaction with their hosts. The most commonly used
      techniques include in vivo expression technology, signature-tagged mutagenesis,
      differential fluorescence induction, and cDNA microarrays, which fall into two
      broad classes: mutagenesis-based technologies and hybridization-based
      technologies. Selective capture of transcribed sequences, a recently emerging
      method, is a hybridization-based technique. This technique is powerful in
      analyzing differential gene expression of the bacteria, with the superb ability
      to investigate the bacterial species with unknown genomic information. Herein, we
      describe the application of this technique in a comparative study of the gene
      expression between two closely related bacteria induced or repressed under a
      variety of conditions.

PMID- 22130988
TI  - Whole-genome RT-qPCR microRNA expression profiling.
AB  - MicroRNAs (miRNAs) are small noncoding RNA molecules that function as negative
      regulators of gene expression. They are essential components of virtually every
      biological process and deregulated miRNA expression has been reported in a
      multitude of human diseases including cancer. Owing to their small size (20-22
      nucleotides), accurate quantification of miRNA expression is particularly
      challenging. In this chapter, we present different RT-qPCR technologies that
      enable whole genome miRNA expression quantification.

PMID- 22130989
TI  - Using quantitative real-time reverse transcriptase polymerase chain reaction to
      validate gene regulation by PTTG.
AB  - Pituitary tumor transforming gene is an important gene which is involved in many
      cellular functions including cell division, DNA repair, organ development,
      expression, and secretion of various angiogenic and metastatic factors.
      Overexpression of this gene has also been reported in many cancers. Understanding
      the molecular pathways induced by this oncogene is therefore important not only
      to understand the development of the disease but also for proper diagnosis and
      treatment. Gene profiling is an excellent tool to identify the genetic
      mechanisms, networks, and pathways associated with a particular disease. Oligo
      nucleotide microarrays can be everybody's choice as a first step to identify the
      global expression of genes involved in the study of interest. Each technique has
      its own limitation. Therefore, further confirmation of the results with a
      different technique is always necessary. Quantitative real-time reverse
      transcriptase polymerase chain reaction (qRT-PCR) is one of the widely used and
      best described techniques to confirm the microarray data. Here, we describe the
      qRT-PCR techniques for gene profiling studies and the methods used for the
      analysis of the output data for further studies.

PMID- 22130990
TI  - FRET-based real-time DNA microarrays.
AB  - We present a quantification method for affinity-based DNA microarrays which is
      based on the real-time measurements of hybridization kinetics. This method, i.e.,
      real-time DNA microarrays, enhances the detection dynamic range of conventional
      systems by being impervious to probe saturation, washing artifacts, microarray
      spot-to-spot variations, and other intensity-affecting impediments. We
      demonstrate in both theory and practice that the time-constant of target
      capturing is inversely proportional to the concentration of the target analyte,
      which we take advantage of as the fundamental parameter to estimate the
      concentration of the analytes. Furthermore, to experimentally validate the
      capabilities of this method in practical applications, we present a FRET-based
      assay which enables the real-time detection in gene expression DNA microarrays.

PMID- 22130991
TI  - 2-D gel electrophoresis: constructing 2D-gel proteome reference maps.
AB  - Two-dimensional gel electrophoresis (2-DE) is the most popular and versatile
      method of protein separation among a rapidly growing array of proteomic
      technologies. Based on two independent biochemical characteristics of proteins,
      it combines isoelectric focusing, which separates proteins according to their
      isoelectric point (pI), and SDS-PAGE, which separates them further according to
      their molecular mass. An evolution of conventional 2-DE is represented by the 2D
      Difference in Gel Electrophoresis (2D-DIGE) that allows sample multiplexing and
      achieving more accurate and sensitive quantitative proteomic determinations. The
      2-DE separation permits the generation of protein maps of different cells or
      tissues and the study, by differential proteomics, of protein expression changes
      associated to the different states of a biological system. In order to identify
      the molecular bases of pathological processes, it is also useful to characterize
      the physiological protein homeostasis in healthy cells or tissues. On these
      grounds, the availability of detailed 2D reference maps could be very useful for
      proteomic studies. The protocol described in this chapter is based on the 2D-DIGE
      technology and has been applied to obtain the first 2-DE reference map of the
      human small intestine.

PMID- 22130992
TI  - The use of antigen microarrays in antibody profiling.
AB  - Technological advances in the field of microarray production and analysis lead to
      the development of protein microarrays. Of these, antigen microarrays are one
      particular format that allows the study of antigen-antibody interactions in a
      miniaturized and highly multiplexed fashion. Here, we describe the parallel
      detection of antibodies with different specificities in human serum, a procedure
      also called antibody profiling. Autoantigens printed on microarray slides are
      reacted with test sera and the bound antibodies are identified by fluorescently
      labeled secondary reagents. Reactivity patterns generated this way characterize
      individuals and can help design novel diagnostic tools.

PMID- 22130993
TI  - Limited proteolysis in proteomics using protease-immobilized microreactors.
AB  - Proteolysis is the key step for proteomic studies integrated with MS analysis.
      Compared with the conventional method of in-solution digestion, proteolysis by a
      protease-immobilized microreactor has a number of advantages for proteomic
      analysis; i.e., rapid and efficient digestion, elimination of a purification step
      of the digests prior to MS, and high stability against a chemical or thermal
      denaturant. This chapter describes the preparation of the protease-immobilized
      microreactors and proteolysis performance of these microreactors. Immobilization
      of proteases by the formation of a polymeric membrane consisting solely of
      protease-proteins on the inner wall of the microchannel is performed. This was
      realized either by a cross-linking reaction in a laminar flow between lysine
      residues sufficiently present on the protein surfaces themselves or in the case
      of acidic proteins by mixing them with poly-lysine prior to the crosslink
      reaction. The present procedure is simple and widely useful not only for
      proteases but also for several other enzymes.

PMID- 22130994
TI  - Mass spectrometry for protein quantification in biomarker discovery.
AB  - Major technological advances have made proteomics an extremely active field for
      biomarker discovery in recent years due primarily to the development of newer
      mass spectrometric technologies and the explosion in genomic and protein
      bioinformatics. This leads to an increased emphasis on larger scale, faster, and
      more efficient methods for detecting protein biomarkers in human tissues, cells,
      and biofluids. Most current proteomic methodologies for biomarker discovery,
      however, are not highly automated and are generally labor-intensive and
      expensive. More automation and improved software programs capable of handling a
      large amount of data are essential to reduce the cost of discovery and to
      increase throughput. In this chapter, we discuss and describe mass spectrometry
      based proteomic methods for quantitative protein analysis.

PMID- 22130995
TI  - High-throughput microtitre plate-based assay for DNA topoisomerases.
AB  - We have developed a rapid, high-throughput assay for measuring the catalytic
      activity (DNA supercoiling or relaxation) of DNA topoisomerases. The assay
      utilizes intermolecular triplex formation between an immobilized triplex-forming
      oligo (TFO) and a triplex-forming region inserted into the plasmid substrate
      (pNO1), and capitalizes on the observation that supercoiled DNA forms triplexes
      more readily than relaxed DNA. Thus, supercoiled DNA is preferentially retained
      by the TFO under triplex-forming conditions while relaxed DNA can be washed away.
      Due to its high speed of sample analysis and reduced sample handling over
      conventional gel-based techniques, this assay can be used to screen chemical
      libraries for novel inhibitors of topoisomerases.

PMID- 22130996
TI  - Microscale thermophoresis as a sensitive method to quantify protein: nucleic acid
      interactions in solution.
AB  - Microscale thermophoresis (MST) is a new method that enables the quantitative
      analysis of molecular interactions in solution at the microliter scale. The
      technique is based on the thermophoresis of molecules, which provides information
      about molecule size, charge, and hydration shell. Since at least one of these
      parameters is typically affected upon binding, the method can be used for the
      analysis of each kind of biomolecular interaction or modification of proteins or
      DNA. Quantitative binding parameters are obtained by using a serial dilution of
      the binding substrate. This section provides a detailed protocol describing the
      analysis of DNA-protein interactions, using the AT-hook peptides as a model
      system that bind to short double-stranded DNA.

PMID- 22130997
TI  - Bioluminescence resonance energy transfer: an emerging tool for the detection of
      protein-protein interaction in living cells.
AB  - In the field of proteomics, numerous advanced technologies have evolved that aim
      to provide the molecular data necessary for an in-depth understanding of
      biological processes. Protein-protein interactions (PPI) are at the heart of
      cellular function and a milestone yet to be achieved is the mapping of a complete
      human interactome. Bioluminescence resonance energy transfer (BRET) has become a
      popular technique to investigate PPI. As BRET enables the detection of PPI in
      living cells, problems associated with in vitro biochemical assays can be
      circumvented, thus making BRET a powerful tool for monitoring interactions of
      virtually all kinds of protein species.

PMID- 22130998
TI  - LuMPIS: luciferase-based MBP-pull-down protein interaction screening system.
AB  - Analyzing the putative interaction partners of an individual protein is one
      approach to elucidate its function. In the LuMPIS protocol, bait and prey
      proteins are expressed with N-terminal maltose binding protein (MBP)- and eGFP
      luciferase (eGFP-luc) tags, respectively. Positive protein-protein interactions
      (PPIs) can be detected after pull-down of the MBP-tagged prey protein using
      amylose beads followed by the bioluminescence detection of the bound eGFP-luc
      tagged bait protein. The LuMPIS technology offers the following advantages: the
      PPIs are detected in the mammalian cell context, the use of two long protein tags
      (i.e., MBP and eGFP-luc) increases the expression levels of genes whose gene
      expression levels are known to be frequently impaired, the use of amylose beads
      for pull-down is much more economic as compared to sepharose beads in combination
      with monoclonal antibodies and finally, the use of an eGFP-luc-tag enables the
      qualitative control of transfection efficiencies by fluorescence microscopy prior
      to starting the assay.

PMID- 22130999
TI  - Yeast two-hybrid screens: improvement of array-based screening results by N- and
      C-terminally tagged fusion proteins.
AB  - Matrix-based yeast two-hybrid screens are an alternative to library-based
      screens. Recent improvements of matrix screens (also called array screens), use
      various pooling strategies as well as novel vectors that increase its efficiency
      while decreasing the false-negative rate, thus increasing reliability. In this
      chapter, we describe a screening strategy that systematically combines N- and C
      terminal fusion proteins using a recently developed vector system.

PMID- 22131000
TI  - Inducible microRNA-mediated knockdown of the endogenous human lamin A/C gene.
AB  - RNA interference (RNAi) enables the suppression, and hence the functional
      analysis, of individual genes. The use of the tetracycline (tet)-controlled
      transcription activation system for RNAi has become a valuable tool for
      conditional gene inactivation both in vitro and in vivo. Here, the generation of
      a conditional RNAi cell line for microRNA (miRNA)-mediated downregulation of the
      endogenous lamin A/C gene is described. A tet-responsive transcription unit,
      encoding a designed miRNA against human lamin A/C, is directly placed into a
      predefined genomic site of our previously developed cell line HeLa-EM2-11ht. This
      chromosomal locus permits the stringent control of miRNA expression, which
      results in the precise adjustment of lamin A/C protein concentrations. The
      utilization of this conditional RNAi system for the controlled inactivation of
      any gene of interest may significantly contribute to the study of gene functions
      under highly defined conditions.

PMID- 22131001
TI  - Multiple-gene silencing using antisense RNAs in Escherichia coli.
AB  - We have developed four expression vectors to express antisense RNAs (asRNAs) by
      which genes of interest are silenced in Escherichia coli. The vectors are all
      IPTG-inducible and co-transformable in any combination and target genes are
      silenced conditionally and concurrently. Furthermore, in order to improve
      silencing efficacy, the vectors are designed to express uniquely shaped antisense
      RNAs, named paired termini antisense RNAs (PTasRNAs). The vectors are useful for
      comprehensive investigation of gene function and are applicable even if the
      target genes are essential for cell growth. Here, we describe methods to
      construct PTasRNA-expressing vectors and to evaluate silencing efficacy.

PMID- 22131002
TI  - Functional screen of zebrafish deubiquitylating enzymes by morpholino knockdown
      and in situ hybridization.
AB  - In order to unfold the function of genes, solely performing mRNA over-expression
      is not enough nowadays. Traditional protein expression experiments, such as
      Western blotting and immunohistochemical staining, could only provide researchers
      the changes of expression levels and/or location of their targets. To make a more
      strong and convincing statement about gene function, it is necessary to perform
      both "gain-of-function" and "loss-of-function" studies. Both assays can be
      performed easily by transfecting DNA plasmid and siRNA in cell culture system;
      while in zebrafish, mRNA and morpholino (MO) microinjection can serve similar
      purposes. It is common for the zebrafish community to carry out microinjection
      experiments to explore a gene function. Instead of making a single knockdown/over
      expression of a gene, we foresee that more and more large-scale screens on
      certain protein families will be performed in the future. Here, based on our
      previous experience in zebrafish "loss-of-function" screening on deubiquitylating
      enzymes, we describe a general work flow, from morpholino designation, in situ
      hybridization, to data analysis, as a reference for researchers who may be
      interested in a similar screen.

PMID- 22131003
TI  - Silencing of gene expression by gymnotic delivery of antisense oligonucleotides.
AB  - Antisense oligodeoxyribonucleotides have been used for decades to achieve
      sequence-specific silencing of gene expression. However, all early generation
      oligonucleotides (e.g., those with no other modifications than the
      phosphorothioate backbone) are inactive in vitro unless administered using a
      delivery vehicle. These delivery vehicles are usually lipidic but can also be
      polyamines or some other particulate reagent. We have found that by employing
      locked nucleic acid (LNA) phosphorothioate gap-mer nucleic acids of 16 mer or
      less in length, and by carefully controlling the plating conditions of the target
      cells and duration of the experiment, sequence-specific gene silencing can be
      achieved at low micromolar concentrations in vitro in the absence of any delivery
      vehicle. This process of naked oligonucleotide delivery to achieve gene silencing
      in vivo, which we have termed gymnosis, has been observed in many both adherent
      and nonadherent cell lines against several different targets genes.

PMID- 22131004
TI  - Polycistronic expression of interfering RNAs from RNA polymerase III promoters.
AB  - In many RNA silencing applications, there is a benefit to expressing multiple
      interfering RNAs simultaneously. This can be achieved by using a single RNA
      polymerase II promoter to express multiple micro(mi)RNA-formatted interfering
      RNAs that are arranged in a polycistronic cluster, mimicking the organization of
      naturally clustered, endogenous miRNAs. While RNA pol III promoters are often
      used to express individual short hairpin (sh) RNAs, we have recently shown that
      pol III promoters can also be used to drive polycistronic expression of miRNA
      formatted interfering RNAs. Here, we present methods for the assembly of
      polycistronic miRNA expression vectors that use pol III promoters. In addition,
      we present methods for testing the potency and the level of expression of each of
      the individual miRNAs encoded in the construct.

PMID- 22131005
TI  - Metabolite analysis of Cannabis sativa L. by NMR spectroscopy.
AB  - NMR-based metabolomics is an analytical platform, which has been used to classify
      and analyze Cannabis sativa L. cell suspension cultures and plants. Diverse
      groups of primary and secondary metabolites were identified by comparing NMR data
      with reference compounds and/or by structure elucidation using 1H-NMR, J
      resolved, 1H-1H COSY, and 1H-13C HMBC spectroscopy. The direct extraction and the
      extraction by indirect fractionation are two suitable methods for the C. sativa
      sample preparation. Quantitative analyses could be performed without requiring
      fractionation or isolation procedures.

PMID- 22131006
TI  - Metabolome analysis of gram-positive bacteria such as Staphylococcus aureus by GC
      MS and LC-MS.
AB  - The field of metabolomics has become increasingly important in the context of
      functional genomics. Together with other "omics" data, the investigation of the
      metabolome is an essential part of systems biology. Beside the analysis of human
      and animal biofluids, the investigation of the microbial physiology by methods of
      metabolomics has gained increased attention. For example, the analysis of
      metabolic processes during growth or virulence factor expression is crucially
      important to understand pathogenesis of bacteria. Common bioanalytical techniques
      for metabolome analysis include liquid and gas chromatographic methods coupled to
      mass spectrometry (LC-MS and GC-MS) and spectroscopic approaches such as NMR. In
      order to achieve metabolome data representing the physiological status of a
      microorganism, well-verified protocols for sampling and analysis are necessary.
      This chapter presents a detailed protocol for metabolome analysis of the Gram
      positive bacterium Staphylococcus aureus. A detailed manual for cell sampling and
      metabolite extraction is given, followed by the description of the analytical
      procedures GC-MS and LC-MS. The advantages and limitations of each experimental
      setup are discussed. Here, a guideline specified for S. aureus metabolomics and
      information for important protocol steps are presented, to avoid common pitfalls
      in microbial metabolome analysis.

PMID- 22131007
TI  - Metabolic fingerprinting using comprehensive two-dimensional gas chromatography
      time-of-flight mass spectrometry.
AB  - Comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry
      (GC * GC-TOF-MS) is applied to the comparative metabolic fingerprinting of
      physiological fluids. Stable isotope-labeled internal standards plus norvaline
      serve as extraction standards and are added to the blanks, controls and patient
      samples prior to protein precipitation with methanol. The extracts are evaporated
      to complete dryness and derivatized in two steps using methoximation with
      methoxylamine hydrochloride (MeOx) and silylation with N-methyl-N-trimethylsily
      trifluoroacetamide (MSTFA). Between derivatization steps a second internal
      standard containing odd-numbered, saturated straight chain fatty acids is added
      for quality control and to normalize retention time shifts. After GC * GC-TOF-MS
      analysis raw data are processed, aligned, and combined in one data matrix for
      subsequent statistical evaluation. Both a custom-made and the NIST 05 library are
      used to preliminarily identify significant metabolites. For verification
      purposes, commercial standards are run individually. Absolute quantification of
      selected metabolites is achieved by using a multi-point calibration curve and
      isotope-labeled internal standards.

PMID- 22131008
TI  - The transrectus sheath preperitoneal mesh repair for inguinal hernia: technique,
      rationale, and results of the first 50 cases.
AB  - INTRODUCTION: Laparoscopic and endoscopic hernia repair popularized the
      preperitoneal mesh position due to promising results concerning less chronic
      pain. However, considerable proportions of severe adverse events, learning
      curves, or added costs have to be taken into account. Therefore, open
      preperitoneal mesh techniques may have more advantages. The open approach to the
      preperitoneal space (PPS) according to transrectus sheath preperitoneal (TREPP)
      mesh repair is through the sheath of the rectus abdominus muscle. This technique
      provides an excellent view of the PPS and facilitates elective or acute hernia
      reduction and mesh positioning under direct vision. In concordance with the
      promising transinguinal preperitoneal inguinal hernia repair experiences in the
      literature, we investigated the feasibility of TREPP. METHODS: A rationale
      description of the surgical technique, available level of evidence for thoughts
      behind technical considerations. Furthermore, a descriptive report of the
      clinical outcomes of our pilot case series including 50 patients undergoing the
      TREPP mesh repair. RESULTS: A consecutive group of our first 50 patients were
      operated with the TREPP technique. No technical problems were experienced during
      the development of this technique. No conversions to Lichtenstein repair were
      necessary. No recurrences and no chronic pain after a mean follow-up of 2 years
      were notable findings. CONCLUSION: This description of the technique shows that
      the TREPP mesh repair might be a promising method because of the complete
      preperitoneal view, the short learning curve, and the stay-away-from-the-nerves
      principle. The rationale of the TREPP repair is discussed in detail.

PMID- 22131009
TI  - Use of the LION procedure on the sensitive branches of the lumbar plexus for the
      treatment of intractable postherniorrhaphy neuropathic inguinodynia.
AB  - PURPOSE: To report on the use of the laparoscopic implantation of neuroprosthesis
      (LION) procedure on the sensitive branches of the lumbar plexus for the treatment
      of refractory postherniorrhaphy neuropathic inguinodynia. METHODS: Laparoscopic
      exposure and implantation of an electrode to the different nerves is undertaken
      by the transumbilical transperitoneal approach. The genitofemoral nerve is
      identified on the anterior surface of the psoas major muscle, the ilioinguinal,
      iliohypogastric, and of the lateral femoral cutaneous nerves on the anterior
      surface of the quadratus lumborum muscle behind the kidney and colon. A
      quadripolar electrode is placed laparoscopically in direct contact with the
      injured nerve(s). RESULTS: All patients included in this series had reported
      failure of all previous treatments. Twenty-three consecutive patients were
      included in this series. Success, defined as visual analog scale (VAS) reduction
      >50%, was obtained in 19 patients. To date (mean follow-up 28.61 months [+/-
      16.2; min. 6 months to max. 68 months]), 11 patients report a reduction of the
      mean VAS of more than 80% and eight report a reduction of between 50 and 80%; the
      mean VAS score could be reduced, so far, from 8.1 (+/- 8.1; range 6-10)
      preoperatively to 3.1 (+/- 2.8; range 0-5) postoperatively (P < 0.001).
      CONCLUSIONS: The presented technique of laparoscopic implantation permits a
      selective implantation and neuromodulation of all sensitive branches of the
      lumbar plexus. These preliminary results suggest that the technique described is
      effective, safe, minimally invasive, and must be indicated in patients after
      failure of all other treatments.

PMID- 22131011
TI  - New strapped porphyrins as hosts for fullerenes: synthesis and complexation
      study.
AB  - New strapped porphyrin-based hosts with different pi-conjugated moieties and
      linkers have been prepared and their ability to bind with fullerenes was studied
      in dilute solution. We found that the ability of these hosts to bind with
      fullerenes strongly depends on their chemical nature and more precisely on the
      substitution pattern of the porphyrin deck. As expected, the more electron-rich
      hosts containing either an exTTF or a porphyrin unit as the strap bind fullerenes
      more efficiently with association constants of up to 3.9 * 10(5) M(-1). The
      results clearly demonstrate the potential of such hosts as a supramolecular
      scaffold for surface immobilization of pristine fullerenes.

PMID- 22131012
TI  - Spatiotemporal variation of macroinvertebrates in relation to canopy cover and
      other environmental factors in Eriora River, Niger Delta, Nigeria.
AB  - Canopy cover is well known to influence the distribution of macroinvertebrates in
      temperate streams. Very little is known about how this factor influences stream
      communities in Afrotropical streams. The effects and possible interactions of
      environmental factors and canopy cover on macroinvertebrate community structure
      (abundance, richness, and diversity) were examined in four stations in Eriora
      River, southern Nigeria bimonthly from May to November 2010. The river supported
      diverse macroinvertebrates in which the upstream sampling stations with dense
      canopy cover were dominated by Decapoda, Ephemeroptera, Odonata, Gastropoda,
      Trichoptera, and Coleoptera while Diptera and Coleoptera were the benthic
      organisms found predominant at downstream stations with less canopy cover. Some
      caddisfly species such as Agapetus agilis, Trichosetodes species and the stonefly
      Neoperla species were present upstream and were found to be potential
      bioindicators for a clean ecosystem. The blood worm Chironomus species and
      Tabanus sp. were abundant at the downstream of the river and are considered
      potential bioindicators for an organically degrading ecosystem. Some
      environmental factors varied temporally with significantly higher
      macroinvertebrate abundance and richness in May. We found out that canopy cover
      and environmental factors affected macroinvertebrates abundance, diversity, and
      richness and that the individual taxon had varying responses to these factors.
      These results help identify the mechanisms underlying the effects of canopy cover
      and other environmental factors on Afrotropical stream invertebrate communities.

PMID- 22131013
TI  - Bio-control of waterborne pathogens using Lactobacillus spp.
AB  - Bacteria play a significant role in water contamination. Chemicals are mostly
      used for the treatment of bacteriologically contaminated water. The use of
      bacterial interactions is a new approach to limit the pathogens' growth.
      Detection of antimicrobial substances produced by lactic acid bacteria against
      the waterborne pathogens is the objective of this work. Microbiological and
      biochemical methods were used to identify lactic acid bacteria having an
      antimicrobial activity. Evaluation of antimicrobial activity with growth kinetic
      measurements was performed. Four isolates of lactic acid bacteria obtained from
      whey and curd were identified. The predominant species belonging to the
      Lactobacillus genera are: Lactobacillus rhamnosus, Lactobacillus sakei,
      Lactobacillus paracasei, and Lactobacillus paraplantarum. The present study
      revealed that the Lactobacillus consortium is able to inhibit Staphylococcus
      aureus's growth along with Escherichia coli and Vibrio species. In mixed culture,
      after 24 h, the Lactobacillus consortium reduces the growth of S. aureus by 2.03
      log; moreover, the growth of the latter bacteria totally ceased after 72 h of
      incubation. The protein produced by the Lactobacillus consortium was responsible
      for arresting the growth of S. aureus.

PMID- 22131014
TI  - Heavy metal accumulation in vegetables grown in a long-term wastewater-irrigated
      agricultural land of tropical India.
AB  - In the present study, the magnitude of contamination of vegetables with heavy
      metals (Pb, Zn, Cd, Cr, Cu and Zn) was determined in a long-term wastewater
      irrigated agricultural land. Heavy metal concentrations in vegetables were
      several folds higher in wastewater-irrigated site compared to clean water
      irrigated area. The wastewater-irrigated crops analysed in this study are heavily
      contaminated with heavy metals. Concentrations of Pb, Zn, Cd and Cr in all the
      sewage-fed vegetables were beyond the safe limit of FAO/WHO and Indian standard.
      Contamination is at its highest level in radish and spinach. Daily intake values
      of Pb, Cd and Ni through consumption of sewage-fed vegetables exceeded the
      recommended oral dose of metal for both adult and children. The study concludes
      that wastewater irrigation led to accumulation of heavy metals in vegetables
      causing potential health risk to consumers.

PMID- 22131015
TI  - Mercury concentration in lichen, moss and soil samples collected from the forest
      areas of Praded and Glacensis Euroregions (Poland and Czech Republic).
AB  - The concentration of mercury was determined in samples of the lichen Hypogymnia
      physodes, the moss Pleurozium schreberi, and the soil humus collected in Polish
      and Czech Euroregions Praded and Glacensis. The sampling sites were located in
      Bory Stobrawskie, Bory Niemodlinskie and Kotlina Klodzka in Poland, and in
      Jeseniki and Gory Orlickie in the Czech Republic. The mean concentrations of
      mercury accumulated in the lichen (0.129 mg g(-1)), in the moss (0.094 mg g(-1))
      and in soil (0.286 mg g(-1)) were fairly close to the corresponding
      concentrations in other low-industrialized regions. The highest concentrations of
      mercury were observed in the lichen and the moss samples from Kotlina Klodzka.
      The primary deposition of mercury was evaluated using the comparison factor,
      defined as the ratio of a difference between the concentrations of a bioavailable
      analyte in lichens and in mosses, to the arithmetic mean of these concentrations.

PMID- 22131017
TI  - Use of remote monitoring in the management of system-related complications in
      implantable defibrillator patients.
AB  - Remote monitoring of implantable defibrillators (ICDs) is designed to minimise
      regular follow-up visits and to facilitate early detection of adverse events.
      With the increased rate of ICD implantations in today's clinical setting and
      multiple device advisories, which pose management challenges, this approach
      becomes very attractive. The aim of this article is to present the role of remote
      monitoring in the detection of system-related complications, its potential
      benefits and its barriers in the outpatient management of ICD patients.

PMID- 22131016
TI  - Oxidative stress response in zebrafish (Danio rerio) gill experimentally exposed
      to subchronic microcystin-LR.
AB  - The worldwide occurrence of cyanobacterial blooms makes it necessary to perform
      environmental risk assessment procedures to monitor the effects of microcytins on
      fish. Oxidative stress biomarkers are valuable tools in this regard. Considering
      that zebrafish (Danio rerio) is a common model species in fish toxicology and the
      zebrafish gill is potentially useful in screening waterborne pollutants, this
      study investigated the oxidative stress response in zebrafish gill exposed to
      subchronic microcystin-LR (MCLR) concentrations (2 or 20 MUg/l) via measurement
      of toxin accumulation, protein phosphatase (PP) activity, and the antioxidant
      parameters (glutathione-S-transferase-GST; glutathione-GSH; superoxide dismutase
      SOD; catalase-CAT; glutathione peroxide-GPx; glutathione reductase-GR), as well
      as levels of hydroxyl radical (OH) and lipid peroxidation (LPO). The results
      showed that after 30 days exposure, MCLR accumulated in zebrafish gill and MCLR
      exposure induced PP activity in gill. A linear inhibition of GST activity and GSH
      content was observed in the gills, revealing that they were involved in the first
      step of MCLR detoxification. The 2 MUg/l MCLR treatment neglectably affected OH
      content and the antioxidant enzymes (SOD, CAT, GPx, and GR), however oxidative
      stress was induced under the 20 MUg/l MCLR treatment in which an enhanced OH
      content and alterations of the antioxidant enzymes were observed in the treated
      gills, although both treatments exerted little effect on LPO level. The principal
      component analysis results indicated that the most sensitive biomarkers of MCLR
      exposure were GST and GSH in zebrafish gill. So, D. rerio could be regarded as a
      suitable bioindicator of MCLR exposure by measuring CAT, GR, GST, and GSH as
      biomarkers.

PMID- 22131018
TI  - Phosphatase of regenerating liver-3 promotes migration and invasion by
      upregulating matrix metalloproteinases-7 in human colorectal cancer cells.
AB  - Phosphatase of regenerating liver (PRL)-3, a member of a subgroup of protein
      tyrosine phosphatases that can stimulate the degradation of the extracellular
      matrix, is over-expressed in metastatic colorectal cancer (CRC) relative to
      primary tumors. To determine whether PRL-3-induced enhancement of migration and
      invasion is dependent on the expression of matrix metalloproteinases (MMPs), PRL
      3 was expressed in DLD-1 human CRC cells. The motility, migration and invasion
      characteristics of the cells were examined, and metastasis to the lung was
      confirmed in a nude mouse using PRL-3-overexpressing DLD-1 cells [DLD-1 (PRL-3)].
      Migration and invasion of the cells were inhibited by phosphatase and
      farnesyltransferase inhibitors. Expression of MMPs was enhanced 3- to 10-fold in
      comparison to control cells, and migration and invasion were partially inhibited
      by small interfering RNA (siRNA) knockdown of MMP-2, -13 or -14. Importantly,
      siRNA knockdown of MMP-7 completely inhibited the migration and invasion of DLD-1
      (PRL-3) cells, whereas overexpression of MMP-7 increased migration. The
      expression of MMP-7 was also downregulated by phosphatase and farnesyltransferase
      inhibitors. It was found that PRL-3 induced MMP-7 through oncogenic pathways
      including PI3K/AKT and ERK and that there is a relationship between the
      expression of PRL-3 and MMP-7 in human tumor cell lines. The expression of MMP-13
      and -14 was very sensitive to the inhibition of farnesyltransferase; however, the
      migration and invasion of DLD-1 (PRL-3) cells did not strongly depend on the
      expression of MMP-13 or -14. These results suggest that the migration and
      invasion of PRL-3-expressing CRC cells depends primarily on the expression of MMP
      7.

PMID- 22131020
TI  - Commentary on "Late gastrointestinal complications of inferior vena cava filter
      placement: case report and literature review".

PMID- 22131019
TI  - Association of cartilage-specific deletion of peroxisome proliferator-activated
      receptor gamma with abnormal endochondral ossification and impaired cartilage
      growth and development in a murine model.
AB  - OBJECTIVE: Long bones develop through the strictly regulated process of
      endochondral ossification within the growth plate, resulting in the replacement
      of cartilage by bone. Defects in this process can result in skeletal
      abnormalities and a predisposition to degenerative joint diseases such as
      osteoarthritis (OA). Studies suggest that activation of the transcription factor
      peroxisome proliferator-activated receptor gamma (PPARgamma) is an important
      therapeutic target in OA. To devise PPARgamma-related therapies in OA, it is
      critical to identify the role of this transcription factor in cartilage biology.
      Therefore, this study sought to determine the in vivo role of PPARgamma in
      endochondral ossification and cartilage development, using cartilage-specific
      PPARgamma-knockout (KO) mice. METHODS: Cartilage-specific PPARgamma-KO mice were
      generated using the Cre/loxP system. Histomorphometric and immunohistochemical
      analyses were performed to assess the patterns of ossification, proliferation,
      differentiation, and hypertrophy of chondrocytes, skeletal organization, bone
      density, and calcium deposition in the KO mice. RESULTS: PPARgamma-KO mice
      exhibited reductions in body length, body weight, length of the long bones,
      skeletal growth, cellularity, bone density, calcium deposition, and trabecular
      bone thickness, abnormal organization of the growth plate, loss of columnar
      organization, shorter hypertrophic zones, and delayed primary and secondary
      ossification. Immunohistochemical analyses for Sox9, 5-bromo-2'-deoxyuridine,
      p57, type X collagen, and platelet endothelial cell adhesion molecule 1 revealed
      reductions in the differentiation, proliferation, and hypertrophy of chondrocytes
      and in vascularization of the growth plate in mutant mice. Isolated chondrocytes
      and cartilage explants from mutant mice showed aberrant expression of Sox9 and
      extracellular matrix markers, including aggrecan, type II collagen, and matrix
      metalloproteinase 13. In addition, chondrocytes from mutant mice exhibited
      enhanced phosphorylation of p38 and decreased expression of Indian hedgehog.
      CONCLUSION: The presence of PPARgamma is required for normal endochondral
      ossification and cartilage development in vivo.

PMID- 22131021
TI  - Update on endovenous laser ablation: 2011.
AB  - In 2001, the use of endovenous laser ablation (EVLA) was introduced to the United
      States to treat superficial venous insufficiency. EVLA has subsequently undergone
      a rapid rise in popularity and usage with a concomitant decrease in traditional
      operative saphenectomy. Since its inception, the use of EVLA to treat superficial
      venous insufficiency has advanced significantly. The efficacy of treatment has
      been validated using both hemoglobin-specific laser wavelength and water-specific
      laser wavelength lasers. Currently, laser optimization is focusing on reducing
      postprocedural sequelae. The clinical parameters that correlate best with
      improved postoperative recovery use lower power/energy settings, water-specific
      laser wavelength lasers, and jacket or radial-emitting tips. Future study is
      still required to assess the durability of treatment at lower power and energy
      settings coupled with jacket or radial-emitting tip fibers. Long-term follow-up
      using duplex imaging is recommended to ensure persistent treatment success.

PMID- 22131022
TI  - A tale of two interferon bioassays: how frustration with discrepant results from
      slightly dissimilar methods can engender discovery.
AB  - This introductory article describes an episode that took place in the mid-1980s
      when the first wave of cytokine discoveries took place. During studies aimed at
      complete purification of human interferon-gamma from crude mitogen-stimulated
      lymphokine preparations, the use of two different antiviral bioassays for the
      cytokine yielded disparate results. Analysis revealed the presence of a
      "contaminant" IFN-like cytokine that was detectable with only one of the two
      assays. Superficially, the contaminant resembled IFN-beta. However, further
      analysis showed that it was not an IFN at all but an IFN-inducing cytokine
      identifiable as interleukin-1.

PMID- 22131023
TI  - The use of real-time quantitative PCR for the analysis of cytokine mRNA levels.
AB  - Over the last decade, real-time-quantitative PCR (RT-qPCR) analysis has become
      the method of choice not only for quantitative and accurate measurement of mRNA
      expression levels, but also for sensitive detection of rare or mutated DNA
      species in diagnostic research. RT-qPCR is based on the standard principles of
      PCR amplification in addition to the use of specific probes or intercalating
      fluorescence dyes. At the end of every cycle, the intercalating dye binds to all
      double-stranded DNA. There is a quantitative relationship between the amount of
      starting DNA and the amount of amplification product during the exponential
      phase. However, to obtain meaningful RT-qPCR data, the quality of the starting
      material (RNA, DNA) and the analysis method of choice are of crucial importance.
      In this chapter, we focus on the details of RNA isolation and cDNA synthesis
      methods, on the application of RT-qPCR for measurements of cytokine mRNA levels
      using Sybr-Green I as detection chemistry, and finally, we discuss the pros and
      contras of the absolute quantification versus relative quantification analysis.
      RT-qPCR is a powerful tool, but it should be "handled" with care.

PMID- 22131024
TI  - Interleukin-27 induces interferon-inducible genes: analysis of gene expression
      profiles using Affymetrix microarray and DAVID.
AB  - We have previously demonstrated that IL-27 is a novel anti-HIV cytokine, which
      inhibits HIV replication in CD4 T cells and macrophages as interferon (IFN)-alpha
      does. To further understand the mechanism of the antiviral effect, we performed
      Affymetrix DNA microarray and gene functional annotation analysis using DAVID
      (the Database for Annotation, Visualization, and Integrated Discovery). DAVID is
      a web-based bioinformatics application that systematically identifies enriched
      biology associated with large gene list(s) derived from high-throughput genomic
      experiments, such as microarray. The enriched annotation terms identified by
      DAVID will give important insights into understanding the biological themes under
      study. Having used the DAVID bioinformatics tools, we have shown that IL-27
      differentially regulates the gene expression between T cells and macrophages. IL
      27 significantly induces IFN-inducible genes including antiviral genes in
      macrophages as does IFN-alpha, suggesting that IL-27 inhibits HIV replication in
      macrophages via a mechanism similar to that of IFN-alpha.

PMID- 22131025
TI  - Quantitative analysis of miRNA expression in epithelial cells and tissues.
AB  - Reliable detection of the microRNA (miRNA) precursor and mature form expression
      levels is a fundamental starting block for more focused studies of the biogenesis
      and functional roles of these important post-transcriptional modulators of gene
      expression. Building on our expertise with miRNA expression programs downstream
      of TGF-beta/Smad signaling in homeostasis as well as in pathological conditions
      associated with epithelial tissues, we present a series of detailed and broadly
      applicable protocols for expression profiling of the mature miRNA forms using
      quantitative real-time PCR TaqMan, both single assays or low-density arrays. We
      next highlight key steps necessary for the detection of primary precursors of
      miRNAs (-pri-miRNAs) to address the initial steps of miRNA biogenesis, and we
      finally review some most widely used computational algorithms for miRNA target
      prediction used to complement experimental identification of the target mRNAs and
      proteins.

PMID- 22131026
TI  - Evaluating posttranscriptional regulation of cytokine genes.
AB  - A wide variety of cytokines are necessary for cell-cell communication in
      multicellular organisms, and cytokine dysregulation has detrimental effects,
      leading to disease states. Thus, it is a necessity that the expression of
      cytokines is tightly controlled. Regulation of cytokine gene expression takes
      place at different levels, including transcriptional and posttranscriptional
      levels. Ultimately, the steady-state levels of cytokine transcripts are
      determined by the equilibrium of transcription and degradation of this mRNA.
      Degradation rates of cytokine mRNAs can be measured in cells by blocking
      transcription with actinomycin D, harvesting RNA after different time points, and
      evaluating mRNA levels over time by northern blot. Cis-acting elements that
      mediate the rapid decay of numerous cytokine transcripts, including AU-rich
      elements (AREs), are found in the 3' untranslated region (UTR) of these
      transcripts. Putative regulatory cis-elements can be cloned into the 3' UTR of a
      reporter transcript in order to assess their function in regulating mRNA decay.
      Cis-elements, such as AREs, regulate cytokine mRNA decay by binding to trans
      acting proteins, such as tristetraprolin or HuR. These RNA-binding proteins can
      be visualized using electromobility shift assays or UV crosslinking assays based
      on their binding to radioactively labeled RNA sequences. RNA-binding proteins
      that regulate cytokine mRNA decay can be purified using an RNA affinity method,
      using their target RNA sequence as the bait. In this chapter, we review the
      methods for measuring cytokine mRNA decay and methods for characterizing the cis
      acting elements and trans-acting factors that regulate cytokine mRNA decay.

PMID- 22131027
TI  - Cloning of cytokine 3' untranslated regions and posttranscriptional assessment
      using cell-based GFP assay.
AB  - Cytokine biosynthesis is tightly regulated by a number of processes, including
      gene expression control. Posttranscriptional control of cytokine gene expression
      offers a fine-tuning mechanism that contributes not only to transient
      biosynthesis of cytokines, but also helps in rapid and early initiation of the
      cytokine response. Deregulation of cytokine biosynthesis has been associated with
      a number of disease conditions, including autoimmune diseases, cancer, and
      others. Thus, there is a need for accurate measurement of posttranscriptional
      gene expression events in cytokine research. The method described here is a cell
      based GFP assay that quantitatively measures posttranscriptional effects. This
      method is used for assessing the effects of modulators and conditions that lead
      to changes in posttranscriptional gene expression during cytokine production or
      for assessment of cytokine action on posttranscriptional events of gene
      expression.

PMID- 22131028
TI  - Integrin-targeted stabilized nanoparticles for an efficient delivery of siRNAs in
      vitro and in vivo.
AB  - Utilizing small interfering RNAs (siRNAs) to silence disease-associated genes
      holds promise as a potential therapeutic strategy. However, the greatest
      challenge for RNAi remains the delivery of siRNA to target tissues or cells.
      Specifically lymphocytes are difficult to transduce by conventional methods but
      represent good targets for anti-inflammatory therapeutics. Integrins are an
      important class of cell adhesion receptors on leukocytes. Antibodies to integrins
      have been used to inhibit inflammatory reactions in patients. Here, we describe a
      strategy to deliver the siRNA cargo to leukocytes by stabilized nanoparticles
      surface-decorated with antibodies to integrin as targeting moieties. A detailed
      methodology for preparation of the integrin-targeted stabilized nanoparticles (I
      tsNPs) and their delivery in vitro and in vivo is discussed.

PMID- 22131029
TI  - Hammerhead ribozyme-mediated knockdown of mRNA for fibrotic growth factors:
      transforming growth factor-beta 1 and connective tissue growth factor.
AB  - Excessive scarring (fibrosis) is a major cause of pathologies in multiple
      tissues, including lung, liver, kidney, heart, cornea, and skin. The transforming
      growth factor-beta (TGF-beta) system has been shown to play a key role in
      regulating the formation of scar tissue throughout the body. Furthermore,
      connective tissue growth factor (CTGF) has been shown to mediate most of the
      fibrotic actions of TGF-beta, including stimulation of synthesis of extracellular
      matrix and differentiation of fibroblasts into myofibroblasts. Currently, no
      approved drugs selectively and specifically regulate scar formation. Thus, there
      is a need for a drug that selectively targets the TGF-beta cascade at the
      molecular level and has minimal off-target side effects. This chapter focuses on
      the design of hammerhead ribozymes, measurement of kinetic activity, and
      assessment of knockdown mRNAs of TGF-beta and CTGF in cell cultures.

PMID- 22131030
TI  - Control of the interferon response in RNAi experiments.
AB  - The RNA interference (RNAi) and interferons have been an uneasy marriage. Ever
      since the discovery of RNAi in mammals, the interferon response has been a feared
      problem. While RNAi became an efficient and widespread method for gene silencing
      in mammals, numerous studies recognized several obstacles, including undesirable
      activation of the interferon response, which need to be overcome to achieve a
      specific and robust RNAi effect. The aim of this text is to provide theoretical
      and practical information for scientists who want to control interferon response
      and other adverse effects in their RNAi experiments.

PMID- 22131031
TI  - shRNA-induced interferon-stimulated gene analysis.
AB  - RNA interference (RNAi) is a cellular mechanism to inhibit the expression of gene
      products in a highly specific manner. In recent years, RNAi has become the
      cornerstone of gene function studies, shortening the otherwise long process of
      target identification and validation. In addition, small interfering RNA (siRNA)
      and short-hairpin RNA (shRNA) therapies are being developed for the treatment of
      a variety of human diseases. Despite its huge potential for gene silencing, a
      hurdle to safe and effective RNAi is the activation of innate immune responses.
      Induction of innate immunity is dose- and sequence-dependent, and is also
      influenced by target tissue and delivery vehicle. Research on the molecular
      mechanisms mediating this response is helping to improve the design of the RNAi
      molecules. Nevertheless, appropriate testing for the presence of this undesired
      effect is needed prior to making conclusions on the outcome of the silencing
      treatment.

PMID- 22131032
TI  - Use of RNA interference to investigate cytokine signal transduction in pancreatic
      beta cells.
AB  - Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by immune
      infiltration of the pancreatic islets resulting in an inflammatory reaction named
      insulitis and subsequent beta cell apoptosis. During the course of insulitis beta
      cell death is probably caused by direct contact with activated macrophages and T
      cells, and/or exposure to soluble mediators secreted by these cells, including
      cytokines, nitric oxide, and free oxygen radicals. In vitro exposure of beta
      cells to the cytokines interleukin(IL)-1beta + interferon(IFN)-gamma or to tumor
      necrosis factor(TNF)-alpha + IFN-gamma induces beta cell dysfunction and
      ultimately apoptosis. The transcription factors NF-kappaB and STAT1 are key
      regulators of cytokine-induced beta cell death. However, little is known about
      the gene networks regulated by these (or other) transcription factors that
      trigger beta cell apoptosis. The recent development of RNA interference (RNAi)
      technology offers a unique opportunity to decipher the cytokine-activated
      molecular pathways responsible for beta cell death. Use of RNAi has been hampered
      by technical difficulties in transfecting primary beta cells, but in recent years
      we have succeeded in developing reliable and reproducible protocols for RNAi in
      beta cells. This chapter details the methods and settings used to achieve
      efficient and nontoxic transfection of small interfering RNA in immortal and
      primary beta cells.

PMID- 22131033
TI  - Ligand affinity chromatography, an indispensable method for the purification of
      soluble cytokine receptors and binding proteins.
AB  - Ligand affinity chromatography separation is based on unique interaction between
      the target analyte and a ligand, which is coupled covalently to a resin. It is a
      simple, rapid, selective, and efficient purification procedure of proteins
      providing tens of thousands fold purification in one step. The biological
      activity of the isolated proteins is retained in most cases thus function is
      revealed concomitantly with the isolation. Prior to the completion of the genome
      project this method facilitated rapid and reliable cloning of the corresponding
      gene. Upon completion of this project, a partial protein sequence is enough for
      retrieving its complete mRNA and hence its complete protein sequence. This method
      is indispensable for the isolation of both expected (e.g. receptors) but mainly
      unexpected, unpredicted and very much surprising binding proteins. No other
      approach would yield the latter. This chapter provides examples for both the
      expected target proteins, isolated from rich sources of human proteins, as well
      as the unexpected binding proteins, found by serendipity.

PMID- 22131034
TI  - In vitro stimulation and detection of IFNalpha production in human plasmacytoid
      dendritic cells.
AB  - Type-1 interferons (IFNs), including IFNalpha/beta, are a family of cytokines
      produced rapidly upon pathogen encounter and crucial for bridging innate and
      adaptive immunity. IFNalpha has been widely appreciated as a multifunctional
      cytokine involved particularly in early immune responses against viral,
      bacterial, and parasitic infections. Although most cells may be competent to
      produce IFNalpha during specific conditions, plasmacytoid dendritic cells (PDCs)
      are unique in their capacity to produce rapid and robust levels in response to
      various pathogens. PDCs to a great extent utilize toll-like receptor (TLR) 7 and
      9, localized in early endosomes, to sense pathogen-associated nucleic acids, and
      initiate the signaling cascade leading to induction of IFNalpha. Here, we provide
      basic protocols for the detection of IFNalpha in individual immune cells,
      particularly PDCs, using flow cytometry. We discuss the key elements for
      successful isolation of PDCs, stimulation, immunostaining, and identification of
      IFNalpha producing cells.

PMID- 22131035
TI  - A sensitive and versatile cytokine bioassay based on type I interferon signaling
      in 2fTGH cells.
AB  - We have designed a sensitive and versatile bioassay for quantification of series
      of cytokines. The assay makes use of chimeric receptors composed of the
      extracellular, ligand-binding part of the cognate cytokine receptor and the
      transmembrane and cytosolic part of the type I interferon receptor. Receptors can
      be homo- (e.g. erythropoietin), di- (e.g. interleukin-5), or even trimeric (e.g.
      interleukin-2). Stable expression of these chimeras in the 2fTGH cell line allows
      an interferon-type signaling, which makes a positive selection in conditioned
      medium possible or a negative selection using a toxic guanine analog. The
      cytokine of interest is quantified by the extent of cell survival or cell
      toxicity respectively, which can be measured by easy and cheap crystal violet
      staining. This bioassay is sensitive in the lower picogram per milliliter range
      and, in contrast to ELISA methods, only measures the concentration of
      biologically active cytokines. Using this approach, hypersensitive 2fTGH cell
      lines have been developed for type I and II interferons, erythropoietin,
      interleukin-2, and interleukin-5.

PMID- 22131037
TI  - Consensus and pool profiles to assist in the analysis and interpretation of
      complex low template DNA mixtures.
AB  - Forensic analysis of low template (LT) DNA mixtures is particularly complicated
      when (1) LT components concur with high template components, (2) more than three
      contributors are present, or (3) contributors are related. In this study, we
      generated a set of such complex LT mixtures and examined two methods to assist in
      DNA profile analysis and interpretation: the "n/2" consensus method (Benschop et
      al. 2011) and the pool profile approach. N/2 consensus profiles include alleles
      that are reproducibly amplified in at least half of the replications. Pool
      profiles are generated by injecting a blend of independently amplified PCR
      products on a capillary electrophoresis instrument. Both approaches resulted in a
      similar increase in the percentage of detected alleles compared to individual
      profiles, and both rarely included drop-in alleles in case mixtures of pristine
      DNAs were used. Interestingly, the consensus and the pool profiles often showed
      differences for the actual alleles detected for the LT component(s). We estimated
      the number of contributors using different methods. Better approximations were
      obtained with data in the consensus and pool profiles compared to the data of the
      individual profiles. Consensus profiles contain allele calls only, while pool
      profiles consist of both allele calls and peak height information, which can be
      of use in (statistical) profile analysis. All advantages and limitations of the
      various types of profiles were assessed, and based on the results we infer that
      both consensus and pool profiles (or a combination thereof) are helpful in the
      interpretation of complex LT DNA mixtures.

PMID- 22131038
TI  - Persistent vegetative state: an ethical reappraisal.
AB  - New knowledge from scientific research on vegetative state (VS) and its
      consequences in clinical practice are reviewed. The ambiguity of the concept of
      consciousness and the difficult issue of its moral significance are then
      examined. The Authors stress the need for longitudinal prognostic studies, the
      promotion of an expert widespread use of standardized behavioural scales, and
      recommend that the ethical debate about VS rely upon the widest consensus of the
      scientific community.

PMID- 22131039
TI  - Vulnerability of an epileptic case to psychosis: sodium valproate with
      lamotrigine, forced normalization, postictal psychosis or all?
AB  - Patients with epilepsy can be considered to be at high risk for developing
      psychotic disorders. Furthermore, there is association between seizure freedom or
      the disappearance of the interictal epileptiform events from the EEG record and
      the occurrence of psychotic symptoms. Also, several newer antiepileptic drugs
      have been reported to induce psychotic symptoms. We present a patient with
      epilepsy who developed psychotic symptoms under the treatment of valproic acid
      (VPA) and lamotrigine (LTG) combination. The mechanism underlying the association
      between LTG, seizure control and development of psychosis are discussed in the
      light of the literature.

PMID- 22131040
TI  - Asymmetric synthesis of ethano-Troger bases using CuTC-catalyzed diazo
      decomposition reactions.
AB  - Nonracemic ethano-bridged Troger bases are prepared using CuTC-catalyzed
      decompositions of diazo compounds. Excellent levels of diastereo- and enantio
      control (dr and ee up to 12:1 and 95% respectively) are now obtained with aryl
      diazoketone precursors.

PMID- 22131041
TI  - Improved outcome of percutaneous radiofrequency ablation in renal cell carcinoma:
      a retrospective study of intraoperative contrast-enhanced ultrasonography in 73
      patients.
AB  - OBJECTIVES: To evaluate the impact of contrast-enhanced ultrasonography (CEUS)
      during percutaneous radiofrequency ablation (PRFA) procedure in renal cell
      carcinoma (RCC). METHODS: From January 2008 to July 2010, 73 patients with
      sporadic unilateral RCC were enrolled to our study (57 men and 16 women, age
      range: 37-78 years, mean age 57.9 years). The diameter of the tumor was 1.7-5.8,
      3.4 cm on average. The patients were divided into two groups depending on the
      intraoperative ultrasonography type: CEUS group and conventional ultrasound
      group. Patients in CEUS group received CEUS before insertion of the electrode,
      and the second CEUS was performed right after the initial ablation to dynamically
      evaluate the images. If there was highly suspicious residue, additional ablation
      and repeated CEUS were applied. Patients in the conventional ultrasound group
      received PRFA guided by gray-scale ultrasound. All of these patients received
      contrast-enhanced computed tomography (CT) examination 7 days after the procedure
      (patients in CEUS group received CEUS conducted with each CT scan), with
      subsequent CT and CEUS assessment at 3, 6, and every 6 months thereafter.
      RESULTS: The mean follow-up period was 22 months (range: 12-42 months). All
      tumors were biopsied before RFA. The local tumor control rate was 94.6% (35/37)
      in the CEUS group and 86.1% (31/36) in the conventional ultrasound group (P <
      0.05); the cancer-specific survival rate and the overall survival rate were 100%.
      The post-RFA (12 months) mean GFR levels were 84.7 +/- 27.5 mL/min/1.73 m(2) (P >
      0.05, compared with pre-GFR: 86.4 +/- 26.2 mL/min/1.73 m(2)) in the CEUS group
      and 81.9 +/- 22.8 mL/min/1.73 m(2) (P > 0.05, compared with pre-GFR: 83.5 +/-
      23.7 mL/min/1.73 m(2)) in the conventional ultrasound group. CONCLUSION:
      Intraoperative CEUS can "real-time" monitor the ablated area during PRFA
      procedure. This technique can help to achieve a higher success rate compared with
      conventional ultrasound. No impact of intraoperative CEUS has been found on GFR
      level.

PMID- 22131042
TI  - Body plan of turtles: an anatomical, developmental and evolutionary perspective.
AB  - The evolution of the turtle shell has long been one of the central debates in
      comparative anatomy. The turtle shell consists of dorsal and ventral parts: the
      carapace and plastron, respectively. The basic structure of the carapace
      comprises vertebrae and ribs. The pectoral girdle of turtles sits inside the
      carapace or the rib cage, in striking contrast to the body plan of other
      tetrapods. Due to this topological change in the arrangement of skeletal
      elements, the carapace has been regarded as an example of evolutionary novelty
      that violates the ancestral body plan of tetrapods. Comparing the spatial
      relationships of anatomical structures in the embryos of turtles and other
      amniotes, we have shown that the topology of the musculoskeletal system is
      largely conserved even in turtles. The positional changes seen in the ribs and
      pectoral girdle can be ascribed to turtle-specific folding of the lateral body
      wall in the late developmental stages. Whereas the ribs of other amniotes grow
      from the axial domain to the lateral body wall, turtle ribs remain arrested
      axially. Marginal growth of the axial domain in turtle embryos brings the
      morphologically short ribs in to cover the scapula dorsocaudally. This concentric
      growth appears to be induced by the margin of the carapace, which involves an
      ancestral gene expression cascade in a new location. These comparative
      developmental data allow us to hypothesize the gradual evolution of turtles,
      which is consistent with the recent finding of a transitional fossil animal,
      Odontochelys, which did not have the carapace but already possessed the plastron.

PMID- 22131043
TI  - The effect of breech presentation on the accuracy of estimated fetal weight.
AB  - To determine whether fetal presentation affects the accuracy of ultrasonographic
      estimated fetal weight (EFW). This is a retrospective cohort study of singleton
      pregnancies that underwent ultrasonographic EFW within 3 weeks of delivery at a
      single institution from 1993 to 2008. Breech presenting fetuses were compared
      with those presenting cephalic. EFW using the Hadlock formula was compared with
      actual birth weight (ABW) and reported as mean difference and mean percentage
      difference. Differences were also considered categorically. Subgroup analyses
      were performed of women who delivered within 4 days of scan and excluding women
      with comorbidities. Ability to detect small and large for gestational age infants
      was compared. Evaluation of 3770 patients, 183 (4.9%) breech presenting and 3587
      (95.1%) cephalic presenting revealed no difference in mean gram difference (
      222.1 g +/- 312.6 vs. -210.7 g +/- 793.2, p = 0.084), respectively, or ability to
      accurately predict within 10% of ABW (adjusted odds ratio [AOR] 1.23; 95% CI,
      0.89,1.69; p = 0.208). Subgroup analyses revealed similar results. There was no
      difference in the ability to detect small and large for gestational age infants.
      Presentation does not demonstrably affect the accuracy of ultrasonographic EFW
      when utilizing the Hadlock formula.

PMID- 22131044
TI  - Ovarian tumors in pregnancy: diagnosis and management.
AB  - Ovarian tumors first diagnosed during pregnancy often present a challenge for
      both the obstetrician and gynecologists providing pregnancy care and for the
      consulting subspecialists. Although the vast majority of these tumors is benign,
      on rare occasions, patients present with tumors that turn out to be malignant
      requiring more comprehensive and extensive surgical procedures that are more
      likely to lead to pregnancy loss. Hence accurate knowledge of tumor
      characteristics, especially the ultrasound appearance and gestational age at
      diagnosis, are key prerequisite for establishing the most effective management
      plan not just for the index but also for future pregnancies. The primary
      objective of the current review is to provide practical guidelines for the
      evaluation and management of ovarian tumors first diagnosed during pregnancy.

PMID- 22131045
TI  - Predictors of successful discontinuation of supplemental oxygen in very low-birth
      weight infants with bronchopulmonary dysplasia approaching neonatal intensive
      care unit discharge.
AB  - We sought to identify factors associated with readiness to discontinue
      supplemental oxygen and to gain weight in very low-birth-weight (VLBW) infants
      with bronchopulmonary dysplasia (BPD) approaching neonatal intensive care unit
      (NICU) discharge. From 2004 to 2009, VLBW infants >=34 weeks' postmenstrual age
      (PMA) on nasal cannula supplemental oxygen were challenged with room air at rest,
      during activity, and feeding as routine care. Outcome and clinical data were
      collected retrospectively. Challenges were divided into derivation and validation
      cohorts. We performed comparative and hierarchical logistic regression analyses,
      constructing a predictive model with passed challenge as outcome. Of 233 infants
      (birth weight 901 +/- 245 g, gestational age 26(6)/(7) +/- 2 weeks), 988 had
      challenges at 38(2)/(7) +/- 3 weeks' PMA. Weight gain was 12.4 +/- 5 g/kg/d in
      the week following passed challenges and 11.2 +/- 5.3 g/kg/d following failed
      challenges (p = 0.08). Increasing weight at time of challenge was associated with
      increased adjusted odds of passing. Increasing capillary pco(2), cannula flow
      rate, pulmonary acuity score, and history of patent ductus arteriosus (PDA)
      ligation decreased odds of passing. Receiver operating characteristic curve area
      was 0.82 in the validation cohort. The model performed well within pco(2) and
      pulmonary acuity score subgroups. Weight, pco(2), cannula flow rate, pulmonary
      acuity score, and history of PDA ligation identify infants with BPD ready to
      maintain saturation and gain weight without supplemental oxygen.

PMID- 22131046
TI  - Catheter-related infection and pathogens of umbilical venous catheterization in a
      neonatal intensive care unit in China.
AB  - We studied the incidence of umbilical venous catheterization (UVC)-related
      infection and pathogens in a neonatal intensive care unit (NICU) in China.
      Patients were grouped into <2000-g UVC or <2000-g non-UVC groups or >=2001-g UVC
      or >=2001-g non-UVC groups. Blood culture and umbilical root skin swab culture
      were taken following UVC insertion and extraction. UVCs were removed after 7 days
      and cultures of UVC tips were performed then. A total of 516 patients were
      enrolled. The incidence of UVC-related septicemia was 9.5%. The incidence of UVC
      related septicemia per 1000 UVC days was 13.6. No significant difference was
      noted between <2000-g UVC and <2000-g non-UVC groups and between >=2001-g UVC
      group and >=2001-g non-UVC groups, in the number of positive blood cultures and
      skin cultures, the percentage of catheter-related septicemia, the incidence of
      catheter-related septicemia per 1000 catheter days, and the increase in the
      number of positive cultures between two skin cultures following UVC insertion and
      extraction. The predominant pathogen in all cultures was gram-positive pathogens.
      Coagulase-negative Staphylococcus was the most frequently noted pathogen. UVC did
      not increase the incidence of catheter-related infection in the NICU. It is
      necessary to consider local pathogen spectrum when choosing antibiotic therapy
      before specific culture results become available.

PMID- 22131047
TI  - Neonatal outcomes of small for gestational age preterm infants in Canada.
AB  - To compare the effect of small for gestational age (SGA) on mortality, major
      morbidity and resource utilization among singleton very preterm infants (<33
      weeks gestation) admitted to neonatal intensive care units (NICUs) across Canada.
      Infants admitted to participating NICUs from 2003 to 2008 were divided into SGA
      (defined as birth weight <10th percentile for gestational age and sex) and non
      small gestational age (non-SGA) groups. The risk-adjusted effects of SGA on
      neonatal outcomes and resource utilization were examined using multivariable
      analyses. SGA infants (n = 1249 from a cohort of 11,909) had a higher odds of
      mortality (adjusted odds ratio [AOR] 2.46; 95% confidence interval [CI], 1.93
      3.14), necrotizing enterocolitis (AOR 1.57; 95% CI, 1.22-2.03), bronchopulmonary
      dysplasia (AOR 1.78; 95% CI, 1.48-2.13), and severe retinopathy of prematurity
      (AOR 2.34; 95% CI, 1.71-3.19). These infants also had lower odds of survival free
      of major morbidity (AOR 0.50; 95% CI, 0.43-0.58) and respiratory distress
      syndrome (AOR 0.79; 95% CI, 0.68-0.93). In addition, SGA infants had a more
      prolonged stay in the NICU, and longer use of ventilation continuous positive
      airway pressure, and supplemental oxygen (p < 0.01 for all). SGA infants had a
      higher risk of mortality, major morbidities, and higher resource utilization
      compared with non-SGA infants.

PMID- 22131049
TI  - Metrologic properties of ultrasound versus clinical evaluation of synovitis in
      rheumatoid arthritis: results of a multicenter, randomized study.
AB  - OBJECTIVE: To evaluate the intraobserver reliability, face validity, and
      discriminant capacity of different global ultrasound (US) scoring systems for
      measuring synovitis in rheumatoid arthritis (RA). METHODS: This study was
      ancillary to a 52-week, multicenter, prospective, randomized, open-label,
      parallel-group outpatient study conducted in patients with moderate RA who were
      randomized to receive either etanercept combined with methotrexate or various
      disease-modifying antirheumatic drugs. A total of 66 different synovitis scoring
      systems were constructed and evaluated, including 11 different joint
      combinations; data derived from clinical findings, gray-scale US, and power
      Doppler US (PDUS); and both binary counts and semiquantitative scores. RESULTS:
      Due to discontinuation of the trial, only 62 patients, a subset of the initially
      planned number of patients, were included in this study. Reliability was found to
      be better for gray-scale US and PDUS than for clinical evaluation of synovitis in
      patients with stable disease between the screening and baseline visits (range for
      intraclass correlation coefficient 0.6, 0.95 for gray-scale US and 0.56, 0.93 for
      PDUS versus 0.31, 0.75 for clinical indices). The median (range) difference in
      the discriminant capacities of clinical indices versus gray-scale US and versus
      PDUS was 0.25 (-0.64, 0.96) and -0.025 (-0.59, 0.53), respectively, in the period
      from baseline to 12 weeks. No relevant differences in metrologic properties were
      observed regarding the number and composition of joints between the different
      scoring systems. Our findings suggested that a simplified scoring system
      referring to gray-scale US and PDUS findings might be sufficient. CONCLUSION: Our
      findings indicate that gray-scale US and PDUS have better reliability than
      generally used clinical indices for evaluating synovitis in RA. PDUS has at least
      as good discriminant capacity as clinical assessment of synovitis for
      distinguishing between treatment arms.

PMID- 22131048
TI  - Body mass index change in adulthood and lung and upper aerodigestive tract
      cancers.
AB  - Body mass index (BMI) has been inversely associated with lung and upper
      aerodigestive tract (UADT) cancers. However, only a few studies have assessed BMI
      change in adulthood in relation to cancer. To understand the relationship between
      BMI change and these cancers in both men and women, we analyzed data from a
      population-based case-control study conducted in Los Angeles County. Adulthood
      BMI change was measured as the proportional change in BMI between age 21 and 1
      year before interview or diagnosis. Five categories of BMI change were included,
      and individuals with no more than a 5% loss or gain were defined as having a
      stable BMI (reference group). Adjusted odds ratios (ORs) and their 95% confidence
      intervals (CIs) were estimated using logistic regression models. Potential
      confounders included age, gender, ethnicity, education, tobacco smoking and
      energy intake. For UADT cancers, we also adjusted for alcohol drinking status and
      frequency. A BMI gain of 25% or higher in adulthood was inversely associated with
      lung cancer (OR 0.53, 95% CI 0.33-0.84) and UADT cancers (OR 0.44, 95% CI 0.27
      0.71). In subgroup analyses, a BMI gain of >=25% was inversely associated with
      lung and UADT cancers among current and former smokers, as well as among current
      and former alcohol drinkers. The inverse association persisted among moderate and
      heavy smokers (>=20 pack-years). The observed inverse associations between
      adulthood BMI gain and lung and UADT cancers indicate a potential role for body
      weight-related biological pathways in the development of lung and UADT cancers.

PMID- 22131050
TI  - SD3, an Arabidopsis thaliana homolog of TIM21, affects intracellular ATP levels
      and seedling development.
AB  - It is poorly understood how plants control their growth by cell division,
      elongation, and differentiation. We have characterized a seedling-lethal mutant
      segregation distortion 3 (sd3) that showed a very dwarf phenotype when grown in
      the light and, in the dark, had short hypocotyls with reduced ploidy levels. The
      corresponding gene of SD3 encodes a protein with high similarity to yeast
      translocase on the inner mitochondrial membrane 21 (TIM21), which is a component
      of the TIM23 complex. Indeed, SD3 protein fused to GFP localized in the
      mitochondria. SD3 overexpression increased cotyledon size in the light and
      hypocotyl thickness in the dark. The expression of genes for several subunits of
      the respiratory-chain complexes III and IV was up-regulated in SD3-overexpressing
      plants. Furthermore, these plants showed high levels of ATP whereas those of sd3
      were low. These results suggested that SD3 induced an increase in cell size by
      raising the expression of the respiratory-chain subunit genes and hence increased
      the intracellular ATP levels. We propose that intracellular ATP levels regulated
      by mitochondria control plant organ size.

PMID- 22131051
TI  - Dual targeting of a processing peptidase into both endosymbiotic organelles
      mediated by a transport signal of unusual architecture.
AB  - As a result of the endosymbiotic gene transfer, the majority of proteins of
      mitochondria and chloroplasts are encoded in the nucleus and synthesized in the
      cytosol as precursor proteins carrying N-terminal transport signals for the 're
      import' into the respective target organelle. Most of these transport signals are
      monospecific, although some of them have dual targeting properties, that is, they
      are recognized both by mitochondria and by chloroplasts as target organelles. We
      have identified alpha-MPP2, one of the two isoforms of the substrate binding
      subunit of mitochondrial processing peptidase of Arabidopsis thaliana, as a novel
      member of this class of nuclear-encoded organelle proteins. As demonstrated by in
      organello transport experiments with isolated organelles and by in vivo
      localization studies employing fluorescent chimeric reporter proteins, the N
      terminal region of the alpha-MPP2 precursor comprises transport signals for the
      import into mitochondria as well as into chloroplasts. Both signals are found
      within the N-terminal 79 residues of the precursor protein, where they occupy
      partly separated and partly overlapping regions. Deletion mapping combined with
      in organello and in vivo protein transport studies demonstrate an unusual
      architecture of this transport signal, suggesting a composition of three
      functionally separated domains.

PMID- 22131052
TI  - RPL1, a gene involved in epigenetic processes regulates phenotypic plasticity in
      rice.
AB  - Organisms can adjust their phenotype in response to changing environmental
      conditions. This phenomenon is termed phenotypic plasticity. Despite its
      ubiquitous occurrence, there has been very little study on the molecular
      mechanism of phenotypic plasticity. In this study, we isolated a rice (Oryza
      sativa L.) mutant, rice plasticity 1 (rpl1), that displayed increased environment
      dependent phenotypic variations. RPL1 was expressed in all tissues examined. The
      protein was localized in the nucleus and its distribution in the nucleus
      overlapped with heterochromatin. The rpl1 mutation led to an increase in DNA
      methylation on repetitive sequences and a decrease in overall histone
      acetylation. In addition, the mutation affected responses of the rice plant to
      phytohormones such as brassinosteroid, gibberellin, and cytokinin. Analysis of
      the putative rice brassinosteroid receptor OsBRI1, a key hormone signaling gene,
      indicated that RPL1 may be involved in the regulation of epigenomic modification
      of the gene. These data suggest that RPL1 regulated phenotypic plasticity likely
      through its involvement in epigenetic processes affecting responses of the plant
      to phytohormones.

PMID- 22131053
TI  - Management of duodenal adenomatosis in FAP: single centre experience.
AB  - Duodenal and ampullary carcinoma in familial adenomatosis (FAP) is the third
      leading cause of FAP related deaths. Management of this condition is a
      challenging. The aim of this study was to evaluate the role of multiple targeted
      endoscopic biopsies and macroscopic appearance as the major determinants for
      surgical intervention. A secondary aim was to assess histological heterogeneity
      through comparing endoscopic biopsies and describe the clinical outcomes of our
      cohort after intervention. We reviewed our FAP surveillance database of 67
      patients, between January 1999--June 2011 undergoing upper GI surveillance and
      where indicated, subsequent surgical intervention. Among 67 patients, 11
      underwent surgical resection. Pancreas-preserving duodenectomy was performed in
      four patients (five procedures), and Whipple's operation in seven patients. The
      average size of polyps was 43 mm (range 17-65 mm), and the average number of
      targeted endoscopic biopsies per lesion was 7.5 (range 5-10). Two cases of high
      grade (severe) dysplasia were diagnosed on endoscopic biopsies each understaged
      compared with the subsequent surgical specimen. All carcinomas identified have
      been resectable with no evidence of local spread or distant metastasis. There was
      one postoperative death, but no cancer related deaths. We identified both cancers
      at an early stage and there were no missed or late diagnoses. There have been no
      recurrences of carcinoma in a more than 7 years follow-up. Due to the
      heterogeneous nature of these lesions, comprehensive macroscopic assessment
      should be complemented with multiple targeted biopsies to improve the chance of
      early detection of advanced lesions.

PMID- 22131055
TI  - Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]
      pyridine.
AB  - Heterocyclic amines (HCAs) are naturally produced during common cooking processes
      for meats and fish. HCAs are metabolized by various enzymes, including
      cytochromes P450, N-acetyl transferases, and sulfotransferases, and their
      bioactivated metabolites are considered to bind to DNA or protein to show
      carcinogenic effects. More than 20 HCAs have been identified, of which 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as 'reasonably
      anticipated to be a human carcinogen' to develop cancers in breast, colon and
      prostate. The purpose of this study was to evaluate human exposure levels of PhIP
      and to understand the role of genetic polymorphisms of enzymes on PhIP
      metabolism. Urine samples were collected from subjects (n = 100) before 3-day
      meat-restricted diets. Subjects consumed grilled chicken, and their blood and
      urine were collected before and after the administration of the chickens to
      investigate genetic polymorphisms and PhIP levels. The mean PhIP levels were 4.22
      +/- 0.12, 0.61 +/- 0.19 and 22.64 +/- 1.00 pg ml(-1) in urine under normal
      conditions and before and after chicken administration, respectively. Among 21
      Single-nucleotide polymorphisms (SNP) of CYP1A1, CYP1A2, NATs and UGTs
      investigated in this study, genotypic groups of CYP1A1/T6235C (MSP I) and CYP1A2/
      2467delT showed significant differences in PhIP excretion (P < 0.05). These
      results suggest that genetic polymorphisms might affect PhIP metabolism, which
      could improve understanding of populations subject to PhIP-derived health risk.

PMID- 22131056
TI  - Musculoskeletal: what's different in children? Dancing, falls: goes for a week
      but pain in the wrist persists.

PMID- 22131057
TI  - MDCT for suspected appendicitis in the elderly: diagnostic performance and
      patient outcome.
AB  - Elderly adults are at increased risk for complications related to both delayed
      diagnosis of appendicitis and to unnecessary appendectomy. We assessed the
      diagnostic performance of computed tomography (CT) in a consecutive elderly
      cohort with clinically suspected appendicitis. CT findings and clinical outcomes
      were analyzed for 262 consecutive adult patients age 65 and older (mean 75.6 +/-
      7.5 years; range 65-94; M/F 111:151) referred for clinically suspected
      appendicitis at a single medical center between January 2000 and December 2009.
      The overall prevalence of proven acute appendicitis in this elderly cohort with
      clinically suspected appendicitis was 16.8% (44/262). CT sensitivity,
      specificity, PPV, and NPV for acute appendicitis were 100% (44/44), 99.1%
      (216/218), 95.7% (44/46), and 100.0% (216/216), respectively. The negative
      appendectomy rate was 2.3% (1/43). The perforation rate was 40.9% (18/44). There
      were no false-negative and two false-positive CT interpretations. All patients
      with appendicitis suspected on CT were hospitalized (44/44), with an average stay
      of 5.7 +/- 3.2 days, and 93.5% (43/46) underwent appendectomy. Overall surgical
      complication rate was 34.9% (15/43). Compared with younger adults over the same
      period, elderly patients had higher rates of perforation and surgical
      complications, and longer hospital stays (p < 0.003). CT is highly accurate for
      the evaluation of clinically suspected appendicitis in elderly patients. Prompt
      diagnosis is important given the higher rates perforation and surgical
      complications relative to younger adults.

PMID- 22131058
TI  - Immunodetection of cyclooxygenase-2 (COX-2) is restricted to tissue macrophages
      in normal rat liver and to recruited mononuclear phagocytes in liver injury and
      cholangiocarcinoma.
AB  - It has been suggested that cyclooxygenase-2 (COX-2)-mediated prostaglandin
      synthesis is associated with liver inflammation and carcinogenesis. The aim of
      this study is to identify the cellular source of COX-2 expression in different
      stages, from acute liver injury through liver fibrosis to cholangiocarcinoma
      (CC). We induced in rats acute and "chronic" liver injury (thioacetamide (TAA) or
      carbon tetrachloride (CCl(4))) and CC development (TAA) and assessed COX-2 gene
      expression in normal and damaged liver tissue by RT-PCR of total RNA. The
      cellular localization of COX-2 protein in liver tissue was analyzed by
      immunohistochemistry as well as in isolated rat liver cells by Western blotting.
      The findings were compared with those obtained in human cirrhotic liver tissue.
      The specificity of the antibodies was tested by 2-DE Western blot and mass
      spectrometric identification of the positive protein spots. RT-PCR analysis of
      total RNA revealed an increase of hepatic COX-2 gene expression in acutely as
      well as "chronically" damaged liver. COX-2-protein was detected in those
      ED1(+)/ED2(+) cells located in the non-damaged tissue (resident tissue
      macrophages). In addition COX-2 positivity in inflammatory mononuclear phagocytes
      (ED1(+)/ED2(-)), which were also present within the tumoral tissue was detected.
      COX-2 protein was clearly detectable in isolated Kupffer cells as well as (at
      lower level) in isolated "inflammatory" macrophages. Similar results were
      obtained in human cirrhotic liver. COX-2 protein is constitutively detectable in
      liver tissue macrophages. Inflammatory mononuclear phagocytes contribute to the
      increase of COX-2 gene expression in acute and chronic liver damage induced by
      different toxins and in the CC microenvironment.

PMID- 22131059
TI  - Bisphenol A exposure modifies methylation of imprinted genes in mouse oocytes via
      the estrogen receptor signaling pathway.
AB  - Bisphenol A (BPA), a synthetic additive used to harden polycarbonate plastics and
      epoxy resin, is ubiquitous in our everyday environment. Many studies have
      indicated detrimental effects of BPA on the mammalian reproductive abilities.
      This study is aimed to test the potential effects of BPA on methylation of
      imprinted genes during oocyte growth and meiotic maturation in CD-1 mice. Our
      results demonstrated that BPA exposure resulted in hypomethylation of imprinted
      gene Igf2r and Peg3 during oocyte growth, and enhanced estrogen receptor (ER)
      expression at the levels of mRNA and protein. The relationship between ER
      expression and imprinted gene hypomethylation was substantiated using an ER
      inhibitor, ICI182780. In addition, BPA promoted the primordial to primary
      follicle transition, thereby speeding up the depletion of the primordial follicle
      pool, and suppressed the meiotic maturation of oocytes because of abnormal
      spindle assembling in meiosis I. In conclusion, neonatal exposure to BPA inhibits
      methylation of imprinted genes during oogenesis via the ER signaling pathway in
      CD-1 mice.

PMID- 22131060
TI  - Back to school: review of school based interventions: comment on Rolfsness and
      Idsoe (2011).
AB  - We comment on a recently published article in the Journal of Traumatic Stress
      that reviewed school-based interventions related to trauma. We point out the
      recent book published by Guilford Press on the International Society for
      Traumatic Stress Studies Practice Guildelines (2009), which also provides a
      thorough review of this literature, and discuss reasons why this review may have
      been missed.

PMID- 22131061
TI  - Firefly flashing under strong static magnetic field.
AB  - Firefly flashing has been the subject of numerous scientific investigations. Here
      we present in vivo flashes from male specimens of three species of fireflies-two
      Japanese species Luciola cruciata, Luciola lateralis and one Indian species
      Luciola praeusta-positioned under a superconducting magnet. When the OFF state of
      the firefly becomes long after flashing in an immobile state under the strong
      static magnetic field of strength 10 Tesla for a long time, which varies widely
      from species to species as well as from specimen to specimen, the effect of the
      field becomes noticeable. The flashes in general are more rapid, and occasionally
      overlap to produce broad compound flashes. We present the broadest flashes
      recorded to date, and propose that the strong static magnetic field affects the
      neural activities of fireflies, especially those in the spent up or 'exhausted'
      condition.

PMID- 22131062
TI  - Muscle CARs and TcRs: turbo-charged technologies for the (T cell) masses.
AB  - A central role for T cells in the control of cancer has been supported by both
      animal models and clinical observations. Accordingly, the development of potent
      anti-tumor T cell immunity has been a long-standing objective of immunotherapy.
      Emerging data from clinical trials that test T cell immune-modulatory agents and
      genetically engineered and re-targeted T cells have begun to realize the profound
      potential of T cell immunotherapy to target cancer. This review will focus on a
      description of recent conceptual and technological advances for the genetic
      engineering of T cells to enhance anti-tumor T cell immunity through the
      introduction of tumor-specific receptors, both Chimeric Antigen Receptors (CAR)
      and T cell receptors (TcR), as well as an overview of emerging data from ongoing
      clinical trials that highlight the potential of these approaches to effect
      dramatic and potent anti-tumor immunity.

PMID- 22131063
TI  - Preferences for genetic testing to identify hereditary colorectal cancer:
      perspectives of high-risk patients, community members, and clinicians.
AB  - The aim of this study was to establish key characteristics that patients,
      consumers, and health professionals value regarding genetic testing (GT) and
      personalized medicine using the example of GT for hereditary Lynch syndrome. We
      conducted a series of focus groups with individuals recruited from a clinic that
      follows those at high risk for hereditary cancer, individuals recruited from the
      community, physicians, and genetic counselors. Participants were presented with
      clinical scenarios about Lynch syndrome testing and asked to identify
      characteristics that they perceived as important in making decisions about GT.
      Forty-two participants (19 community members, 8 high-risk and cancer patients, 3
      genetic counselors, and 8 physicians) participated. Among community members and
      patients, the most frequently discussed considerations were the personal impact
      of GT and family impact, respectively. Among physicians, the most frequently
      discussed topic was the characteristics of genomic services (e.g., test
      invasiveness); among genetic counselors, the most frequently discussed topic was
      evidence and recommendations. A variety of test characteristics were important in
      decision making about GT. High-risk patients, community members, and health care
      providers had different priorities. Health care professionals should be aware of
      differences between their own considerations about GT and those that are
      important to patients.

PMID- 22131064
TI  - Assessment of cancer education seminars for Appalachian populations.
AB  - Cancer education seminars for Appalachian populations were conducted to: (1)
      increase knowledge of existing cancer disparities, (2) disseminate findings from
      Appalachian community-based participatory research (CBPR) projects, and (3)
      foster CBPR capacity building among community members by promoting social
      networking. Evaluation of the seminars was completed by: (1) using pre-post
      surveys to assess changes in knowledge and attitudes at three regional and one
      national seminar and (2) measuring a change in the social network patterns of
      participants at a national seminar by analyzing the names of individuals known at
      the beginning and at the end of the seminar by each participant. Among
      participants, there was a significant increase in knowledge of Appalachian cancer
      disparities at two seminars [national, t(145) = 3.41, p = 0.001; Pennsylvania,
      t(189) = 3.00, p = 0.003] and a change in attitudes about Appalachia at one
      seminar [Ohio t(193) = -2.80, p = 0.006]. Social network analysis, operationally
      defined for this study as familiarity with individuals attending the conference,
      showed participation in the national seminar fostered capacity building for
      future CBPR by the development of new network ties. Findings indicate that short
      term outcomes of the seminars were accomplished. Future educational seminars
      should consider using social network analysis as a new evaluation methodology.

PMID- 22131065
TI  - An increase in HPV-related knowledge and vaccination intent among parental and
      non-parental caregivers of adolescent girls, age 9-17 years, in Appalachian
      Pennsylvania.
AB  - A theory and community-based educational intervention was designed to increase
      HPV-related knowledge and intent to vaccinate adolescent girls, against human
      papillomavirus (HPV) in Appalachia, a region with high cervical cancer incidence
      and mortality. An HPV educational session was conducted with immediate pre-/post
      test questionnaires and 1-month follow-up telephone interview. McNemar tests and
      paired t tests evaluated change in individual knowledge variables and change in
      overall knowledge and intent to vaccinate against HPV, respectively. Of 117
      attendees, 38 (32.5%) were parents of vaccine-eligible daughters and 79 (67.5%)
      non-parental caregivers. HPV-related knowledge increased for all participants (p
      < 0.0001) and among parents (p < 0.0001). Intent to vaccinate daughters within 1
      month increased among parents (p = 0.002). Of nine (23.7%) parents who completed
      the follow-up interview, 100% reported the intervention as helpful and 44.4%
      reported that they started vaccination. Our education intervention was associated
      with increased HPV-related knowledge and intent to vaccinate girls in Appalachia
      against HPV.

PMID- 22131066
TI  - Outcomes of a cancer clinical trial matching service.
AB  - The American Cancer Society (ACS) and Coalition of Cancer Cooperative Groups
      (CCCG) provide a clinical trial (CT) information/matching/eligibility service
      (Clinical Trials Matching Service [CTMS]). Patients' demographic and clinical
      data, enrollment status, and self-reported barriers to CT participation were
      analyzed to assess enrollment rates and determinants of enrollment. During 3
      years beginning October 1, 2007, the CTMS served 6,903 patients via the ACS call
      center. Among the 1,987 patients with follow-up information on enrollment, 219
      (11.0%) enrolled in a CT; 48 of these 219 enrollees chose a CT they found via the
      CTMS. Patients were less likely to enroll if they had poor ECOG performance
      status (P = 0.032); were African American (P = 0.0003), were uninsured or had
      Medicaid coverage (P = 0.024), or had lower stage disease (P = 0.018). Enrollment
      varied by trial type/cancer site/system (P = .026). Several barriers
      significantly predicted nonenrollment. Broader availability of a CTMS might help
      improve patient participation in cancer clinical trials.

PMID- 22131068
TI  - Novel mesoporous NiO/HTiNbO5 nanohybrids with high visible-light photocatalytic
      activity and good biocompatibility.
AB  - Mesoporous nanohybrids of NiO nanoparticles and HTiNbO(5) nanosheets have been
      successfully synthesized by first exfoliating layered HTiNbO(5) in
      tetrabutylammonium hydroxide (TBAOH) to obtain HTiNbO(5) nanosheets, then
      reassembling with a nickel precursor and finally heating with urea. The resulting
      samples were characterized by X-ray diffraction (XRD), high resolution
      transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), X
      ray photoelectron spectroscopy (XPS), UV-vis spectroscopy, photoluminescence
      spectroscopy (PL) and N(2) adsorption-desorption measurements. It was found that
      the as-prepared nanohybrids had a relatively large interlayer spacing of 1.05 nm.
      After calcination, the titanoniobate nanosheet was still retained and the pore
      size of the resulting nanohybrids became larger. Compared with the original
      HTiNbO(5), the obtained nanohybrids were mesoporous with a greatly expanded
      surface area (~75-115 m(2) g(-1)), a much strengthened absorption in the UV light
      region and a visible-light response. Nickel atoms were present in the form of Ni
      O in the nanohybrid, and NiO nanoparticles were homogeneously distributed with an
      average particle size of 2-3 nm, giving rise to the visible light response. The
      catalytic activities of the obtained samples were evaluated by the
      photodegradation of RhB solution under visible light irradiation. The
      introduction of urea during the calcination process not only increased the
      thermal stability and surface area, but also decreased the rate of recombination
      of photogenerated holes and electrons, leading to a greatly enhanced
      photocatalytic activity of the resulting nanohybrids. The dye molecules were
      mainly degraded to aliphatic organic compounds and partially mineralized to CO(2)
      and/or CO, rather than being simply decolorized. In addition, cell viability
      results for HepG2 cells show that the as-prepared sample have good
      biocompatibility.

PMID- 22131069
TI  - Epirubicin potentiates recombinant adeno-associated virus type 2/5-mediated TRAIL
      expression in fibroblast-like synoviocytes and augments the antiarthritic effects
      of rAAV2/5-TRAIL.
AB  - OBJECTIVE: Synovial cells in rheumatoid synovium display abnormal proliferation,
      which leads to joint destruction. TRAIL has been described as a proapoptotic
      factor in fibroblast-like synoviocytes (FLS). This study was undertaken to
      investigate the functions of rAAV2/5-TRAIL in human FLS and in arthritic mice.
      METHODS: Primary human FLS were infected with rAAV2/5-TRAIL in the presence or
      absence of epirubicin. Transgene expression was monitored by both enzyme-linked
      immunosorbent assay and flow cytometry. The disease-modulating activity of
      epirubicin plus rAAV2/5-TRAIL was investigated in mice with collagen-induced
      arthritis (CIA). RESULTS: Subtoxic doses of epirubicin potentiated rAAV2/5
      mediated TRAIL expression in FLS and simultaneously enhanced the sensitivity of
      FLS to TRAIL. Epirubicin treatment up-regulated death receptor 4 (DR-4) and DR-5
      expression and down-regulated FLIP expression, thereby enhancing the activation
      of procaspase 3, procaspase 8, and procaspase 9. An in vivo study showed that the
      combination of rAAV2/5-TRAIL gene therapy and epirubicin chemotherapy provided
      augmented antiarthritic effects in a mouse model of CIA. The intraarticular
      injection of rAAV2/5-TRAIL combined with epirubicin treatment significantly
      reduced the severity and incidence of CIA and joint swelling in the animals.
      Histologic evaluations revealed that inflammatory cell infiltration, cartilage
      destruction, and bone erosion were significantly reduced in the joints of the
      mice receiving the synthetic treatment. Results of a viral genome copy number
      assay indicated that epirubicin dramatically augmented the expression of rAAV2/5
      TRAIL without altering its tissue distribution. CONCLUSION: These results suggest
      that epirubicin enhances the antiarthritic effect of rAAV2/5-TRAIL and that
      combination treatment might be an important therapeutic alternative, with
      practical significance for rheumatoid arthritis.

PMID- 22131070
TI  - Resistance versus aerobic exercise training in chronic heart failure.
AB  - It is now accepted that exercise training is a safe and effective therapeutic
      intervention to improve clinical status, functional capacity, and quality of life
      in people with chronic heart failure (CHF). Nevertheless, this therapeutic
      modality remains underprescribed and underutilized. Both aerobic and resistance
      training improve exercise capacity and may partially reverse some of the cardiac,
      vascular, and skeletal muscle abnormalities in individuals with CHF. Aerobic
      training has more beneficial effects on aerobic power (peak oxygen consumption)
      and cardiac structure and function than resistance exercise training, while the
      latter is more effective for increasing muscle strength and endurance and
      promoting favorable arterial remodeling. Combined aerobic and resistance training
      is the preferred exercise intervention to reverse or attenuate the loss of muscle
      mass and improve exercise and functional capacity, muscle strength, and quality
      of life in individuals with CHF. The challenge now is to translate these research
      findings into clinical practice.

PMID- 22131071
TI  - Stress and expression of cyclooxygenases (cox1, cox2a, cox2b) and intestinal
      eicosanoids, in Atlantic salmon, Salmo salar L.
AB  - Prostaglandin H synthetases (cyclooxygenases) catalyze the initial reactions
      leading to prostanoids in animals. They form interesting links between diet and
      fish physiology as the type and nature of eicosanoids are affected by dietary
      lipid sources. Their expression is likely to be affected by tissues and
      environmental conditions leading to altered amount and ratio of eicosanoids.
      These mechanisms are, however, poorly understood in fish. In the present study,
      Atlantic salmon Salmo salar L. (1,000 g, 10 degrees C, seawater) were subjected
      to acute chasing stress. Liver, kidney, spleen, gill, muscle, midgut and hindgut
      were extracted before and 1 h post-stress and analyzed for mRNA expression of
      cox1, cox2a and cox2b. Intestinal samples were further sampled over 24 h for both
      cox expression and analysis of 15 eicosanoids and isoprostanes of the n-3 and n-6
      series. Results show a highly variable but consecutively expression of cox1,
      cox2a and cox2b in most of the tissues analyzed. Low levels were only found for
      cox2a in liver and cox2b in liver and kidney. The study reveals the general trend
      that cox1 is about 10 times the level of cox2b, which again is about 10 times the
      level of cox2a. Cox2b shows the highest level of expression in the gills
      indicating a possible higher requirement for this protein in gills. Imposing
      stress to the fish induces a temporal increase in the expression of cox2a in the
      midgut, while the gene expression of the other genes is not affected in any of
      the tissues analyzed. There is, however, a general tendency to increased
      expression of both cox2 genes that merits further studies. Stress had a profound
      effect on the intestinal eicosanoid content which showed a general decrease in
      midgut sections after stress that persisted for at least 24 h.

PMID- 22131073
TI  - [The manual "Problematic use and dependence of prescipted drugs" in daily routine
      care -  a study among participants in a training to qualify in "primary addiction
      treatment"].
AB  - BACKGROUND: To strengthen the position of physicians regarding problematic use
      and dependence of prescripted drugs a manual was issued by the German Medical
      Association in 2007.  A study among participants in a training to qualify in
      "primary addiction treatment" was conducted. The utilisation of the manual, its
      relevance for routine care and self-estimated changes in drug prescription were
      examined. METHODS: All 542 participants in training courses between 1.9.2008 and
      31.12.2009 were asked about participation in a survey 12 weeks later. A number of
      267 took part in this investigation. RESULTS: A proportion of 60,7 % among GPs
      that received the manual dealt with them beyond the training course. From 178
      physicians, who confirmed the provision of drug prescription, a number of 56
      stated changes in their drug prescription. A higher probabilty for changes in
      drug prescription was given in case of a high percentage of new informations that
      could be culled from the manual. CONCLUSION: The interest for the manual beyond
      the training course and the amount of self-estimated changes in drug prescription
      should encourage to use this within training measures in a systematic way.

PMID- 22131072
TI  - Androgens regulate Hedgehog signalling and proliferation in androgen-dependent
      prostate cells.
AB  - Prostate cancer (PCa) is androgen sensitive in its development and progression to
      metastatic disease. Hedgehog (Hh) pathway activation is important in the
      initiation and growth of various carcinomas including PCa. We and others have
      observed aberrations of Hh pathway during the progression of PCa to the
      castration-resistant state. The involvement of androgen signalling in Hh pathway
      activation, however, remains largely elusive. Here we investigate the direct role
      of androgen signalling on Hh pathway. We examined the effect of Dihydrosterone
      (DHT), antiandrogen, bicalutamide, and Hh pathway inhibitor, KAAD-cyclopamine in
      four human prostate cell lines (two cancerous: LNCaP, VCaP, and two normal: PNT2
      and PNT2-ARm which harbours a mutant version of androgen receptor (AR) that is
      commonly found in LNCaP). Cell proliferation as well as Hh pathway members (SHH,
      IHH, DHH, GLI, PTCH) mRNA expression levels were assessed. We showed that KAAD
      cyclopamine decreased cell proliferation of DHT-stimulated LNCaP, VCaP and PNT2
      ARm cells. SHH expression was found to be downregulated by DHT in all AR
      posititve cells. The negative effect of DHT on SHH expression was counteracted
      when cells were treated by bicalutamide. Importantly, KAAD-cyclopamine treatment
      seemed to inhibit AR activity. Moreover, bicalutamide as well as KAAD-cyclopamine
      treatments induced GLI and PTCH expression in VCaP and PNT2-ARm. Our results
      suggest that Hh pathway activity can be regulated by androgen signalling.
      Specifically, we show that the DHT-induced inhibition of Hh pathway is AR
      dependent. The mutual interaction between these two pathways might be important
      in the regulation of cell proliferation in PCa.

PMID- 22131074
TI  - [Recurrent hypoglycemia and a large intraabdominal tumor  in a 61-year-old
      woman].
AB  - HISTORY AND ADMISSION FINDINGS: A 61-year-old woman was found unconscious by her
      husband. The emergency doctor detected hypoglycemia (blood glucose 1.7 mmol/l).
      This was the first such event, the patient had not been known to have diabetes
      mellitus. At admission the physical examination and the laboratory findings
      revealed no abnormalities. INVESTIGATIONS: A fasting test was aborted shortly
      after the start because of the onset of neurological symptoms. An insulinoma was
      excluded by detecting suppressed levels of insulin and C-peptide. Computed
      tomography of the abdomen revealed a mesenteric tumour of 9 cm in diameter, which
      was identified immunhistologically as a grade 1 follicular lymphoma (FL).  After
      exclusion of endocrinological causes the recurrent hypoglycaemia was diagnozed as
      part of a paraneoplastic syndrome associated with a non-islet cell tumour
      hypoglycaemia (NICTH) with a newly diagnosed FL. TREATMENT AND COURSE: Specific
      medication with the CD20 antibody rituximab (375 mg/m2, once per week for a total
      of four cycles) was initiated. There were no further episodes of hypoglycaemia.
      After one year the patient remains free of any symptoms. CONCLUSIONS: After
      exclusion of any endocrinological reasons for hypoglycemia, differential
      diagnosis should include NICTH as paraneoplastic syndrome. In rare cases a
      hematological malignancy may be the underlying disease. The specific treatment of
      this disease likewise represents the causal treatment of NICTH.

PMID- 22131075
TI  - [29-year-old patient with chronic persistent cough. Tracheal bronchus].

PMID- 22131076
TI  - [Geriatrics: an introduction from a gerontological point of view].
AB  - Geriatrics is in comparison to the other medical professions a relatively new
      discipline. The calendarical age is not suitable for the characterization of its
      patient population, the multimorbid old patients. The biofunctional age in terms
      of the ICF is a better choice. It is characterized in part by physical,
      psychical, and social context-factors, which can be analysed by geriatric
      assessments. A better cooperation between basic science orientated gerontological
      disciplines with the geriatrics will be, beside the implementation into the
      university medicine and the standardized uniform professional training, of
      essential importance for the further development of geriatric medicine.

PMID- 22131077
TI  - [Conversion from a calcineurin inhibitor to a sirolimus-based therapy after renal
      transplantation - An update of existing recommendations].

PMID- 22131078
TI  - [Who protects physicians and patients from guidelines?].

PMID- 22131079
TI  - [Pneumococcal sepsis in aged patients - implications for the vaccination of
      seniors against pneumococci].
AB  - In the years 2005-2010 pneumococci were isolated in the Limbach
      laboratory/Heidelberg from blood cultures of 1,085 patients. Obviously, older
      patients are more prone to these bacteria, since 66 % of the patients were older
      than 60 years. All isolates were susceptible to cefotaxime; 3 % of isolates were
      resistant to penicillin, 2 % were resistant to levofloxacin and 15 % were
      resistant to erythromycin. From 457 out of the isolates serotyping was achieved:
      more than 80 % of the isolates were covered by the 23-valent vaccine. This means
      that particularly old people should be vaccinated against pneumococci, because
      they will profit probably most from such preventive measurements.

PMID- 22131080
TI  - Fungemia due to Rhodotorula mucilaginosa in an immunocompetent, critically ill
      patient.
AB  - Infections due to the yeast Rhodotorula are rare in humans. R. mucilaginosa is
      responsible for the majority of human cases, and immunocompromised individuals
      with central venous catheters are at greatest risk. There are few reports of
      bloodstream infections due to R. mucilaginosa in immunocompetent patients. We
      present a case report of fungemia due to R. mucilaginosa in an immunocompetent,
      critically ill patient, with good evolution with catheter removal and fluconazole
      therapy. We briefly review the spectrum of infections due to R. mucilaginosa and
      the management of bloodstream infections due to this yeast.

PMID- 22131081
TI  - A new staphylococcal cassette chromosome mec IV encoding a novel cell-wall
      anchored surface protein in a major ST8 community-acquired methicillin-resistant
      Staphylococcus aureus clone in Japan.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), which
      has staphylococcal cassette chromosome mec (SCCmec) type IV or V, has become a
      major concern worldwide. However, the involvement of SCCmecIV (or V) in community
      spread is still not fully understood. In this study, we searched for a possible
      adhesin gene in SCCmecIV, which could contribute to community colonization and
      spread. For this, we determined the entire SCCmecIV sequence of CA-MRSA in Japan,
      which was previously characterized as multilocus sequence type (ST) 8/SCCmecIVx
      (type IV with unknown subtypes). The SCCmecIV was 25,555 bp in size and flanked
      by 15-bp att sequences. The 8.2-kb J1 region was unique (through recombination)
      and contained a 4.8-kb orf (named spj), encoding for a novel 1,604-amino acid
      cell-wall-anchored surface protein (CWASP/J) with the LPXTG motif. The spj gene
      had no homology with any sequence submitted to GenBank, indicating a novel gene
      sequence. The new SCCmec IV was tentatively designated SCCmecIVl. A PCR assay
      specific to the spj gene was developed. Two steps of PCR for detection of the spj
      gene and SCCmecIV showed that ST8/SCCmecIVl MRSA is spreading widely in the
      community. This study demonstrates a new SCCmecIV encoding a novel CWASP, which
      could contribute to community spread as a potential colonization factor. Because
      ST8 CA-MRSA with SCCmecIVl causes skin and soft tissue infections and
      occasionally invasive infections, surveillance is needed.

PMID- 22131084
TI  - Expression of concern.

PMID- 22131085
TI  - Discovery of common urinary biomarkers for hepatotoxicity induced by carbon
      tetrachloride, acetaminophen and methotrexate by mass spectrometry-based
      metabolomics.
AB  - Liver toxicity represents an important healthcare issue because it causes
      significant morbidity and mortality and can be difficult to predict before
      symptoms appear owing to drug therapy or exposure to toxicants. Using metabolomic
      techniques, we discovered common biomarkers for the prediction of hepatotoxicity
      in rat urine using mass spectrometry. For this purpose, liver toxicity was
      induced by 5 days of oral administration of carbon tetrachloride (1 ml kg(-1) per
      day), acetaminophen (1000 mg kg(-1) per day) and methotrexate (50 mg kg(-1) per
      day). Serum levels of alkaline phosphatase aspartate aminotransferase, alanine
      aminotransferase and histopathology in liver tissue were then checked to
      demonstrate liver toxicity. Global metabolic profiling with UPLC-TOF-MS
      (ultraperformance liquid chromatography-mass spectrometry), multivariate analysis
      (partial least square-discriminant analysis, hierarchical analysis) and database
      searching were performed to discover common biomarkers for liver toxicity induced
      by these three compounds. Urinary concentrations of the newly discovered
      biomarkers were then quantified to confirm them as biomarkers of hepatotoxicity
      with targeted metabolic profiling using GC (gas chromatography)-MS and CE
      (capillary electrophoresis)-MS. In the results, steroids, amino acids and bile
      acids were metabolically changed between the control and drug-treated groups in
      global metabolic profiling; 11beta-hydroxyandrosterone, epiandrosterone, estrone,
      11-dehydrocorticosterone, glycine, alanine, valine, leucine, dl-ornithine, 3
      methylhistidine, cholic acid and lithocholic acid were selected as liver toxicity
      biomarkers after performing targeted metabolic profiling. In conclusion, we
      discovered metabolite biomarkers belonging to three different metabolic pathways
      to check for liver toxicity with mass spectrometry from a metabolomics study that
      could be used to evaluate hepatotoxicity induced by drugs or other toxic
      compounds.

PMID- 22131086
TI  - Effects of plyometric training on passive stiffness of gastrocnemii muscles and
      Achilles tendon.
AB  - Plyometric training is commonly used to improve athletic performance; however, it
      is unclear how each component of the muscle-tendon complex (MTC) is affected by
      this intervention. The effects of 14 weeks of plyometric training on the passive
      stiffness of the gastrocnemii muscles and Achilles tendon was determined
      simultaneously to assess possible local adaptations of elastic properties. The
      passive force-length relationship of the gastrocnemii MTC and elongation of the
      gastrocnemii muscles were determined using ultrasonography during passive cyclic
      stretching in 19 subjects divided into trained (n = 9) and control (n = 10)
      groups. An upward trend in stiffness of the gastrocnemii MTC (P = 0.09) and a
      significant increase in the intrinsic gastrocnemii muscle stiffness were found (P
      < 0.05). In contrast, no significant change in gastrocnemii tendon stiffness, or
      in muscle and tendon geometry, was determined (P > 0.05). Considering the lack of
      change in gastrocnemii muscle geometry, the change in the gastrocnemii muscle
      stiffness may be mainly due to a change in the intrinsic mechanical properties of
      the muscular tissues.

PMID- 22131087
TI  - Climbing-specific finger flexor performance and forearm muscle oxygenation in
      elite male and female sport climbers.
AB  - Climbing performance relies to a great extent on the performance of the finger
      flexor muscles. Only a few studies investigated this performance in top class
      climbers and only one study compared gender-specific differences. This study
      investigated the climbing-specific finger flexor strength and endurance and
      related muscular oxygenation in 12 elite female and male climbers and 12 non
      climbers. After the assessment of maximum voluntary finger flexor contraction
      (MVC), two isometric finger flexor endurance tests were performed at 40% MVC
      until exhaustion. A continuous isometric test was followed by an intermittent
      isometric test (10 s contraction, 3 s rest). Changes in oxygenation of finger
      flexor muscles were recorded using near infrared spectroscopy. MVC and strength
      to-weight ratio were greater in climbers than non-climbers (P = 0.003; P < 0.001)
      and greater in men than women (P < 0.001; P = 0.002). Time to task failure for
      the intermittent test and the force-time integrals for the continuous and the
      intermittent test were also significantly greater in climbers (P = 0.030; P =
      0.027; P = 0.005). During the intermittent test, re-oxygenation of the working
      muscles was faster in climbers (P < 0.05) without gender-specific differences.
      Close correlations were demonstrated between the best on-sight climbing
      performance and strength-to-weight ratio (r (2) = 0.946, P < 0.001) only in
      female climbers. The superior intermittent finger flexor endurance of climbers
      over non-climbers may be explained by the faster re-oxygenation of the finger
      flexor muscles during the short rest phases.

PMID- 22131088
TI  - Novel integrated robotic approach for suprapancreatic D2 nodal dissection for
      treating gastric cancer: technique and initial experience.
AB  - BACKGROUND: Robotic surgery for the treatment of gastric cancer has been
      reported, but the technique is not yet established. The objective of this study
      was to assess the feasibility and safety of our novel integrated procedure for
      robotic suprapancreatic D2 nodal dissection during distal gastrectomy. METHODS:
      At our hospital from January 2009 to December 2010, a total of 25 consecutive
      cases of gastric cancer were treated by robotic distal gastrectomy with
      intracorporeal Billroth I reconstruction. These patients were enrolled in a
      prospective study to assess the safety and feasibility of robotic distal
      gastrectomy with nodal dissection by our novel integrated approach, which
      consists of three elements: arm formation, the surgical approach, a cutting
      device. To evaluate the learning curves involved in this approach,
      clinicopathologic features and surgical outcomes were compared between the
      initial (n = 12) and late (n = 13) phases. RESULTS: All operations were completed
      without the need for open or conventional laparoscopic surgery. The mean
      operating time was 361 +/- 58.1 min (range 258-419 min), and blood loss recorded
      was 51.8 +/- 38.2 ml (range 4-123 ml). The median number of retrieved lymph nodes
      was 44.3 +/- 18.4 (range 26-95). R0 resection was accomplished in all cases.
      There were no deaths or complications related to pancreatic damage. Operating
      time and surgeon console time for the late phase were significantly shorter than
      those for the initial phase. CONCLUSIONS: Our novel robotic approach for D2 nodal
      dissection in gastric cancer is feasible and safe.

PMID- 22131089
TI  - An elixir for the troubled future of general surgery in South Africa.

PMID- 22131090
TI  - Adverse outcomes in patients with postoperative ascites after liver resection for
      hepatocellular carcinoma.
AB  - BACKGROUND: Postoperative ascites (POA) is a common complication after liver
      resection (LR). The aim of the present study was to identify the risk factors for
      developing POA and to evaluate its clinical significance in the prognosis of
      patients with hepatocellular carcinoma (HCC). METHODS: We performed a
      retrospective analysis of data obtained from 651 patients who underwent LR for
      the treatment of HCC between January 2001 and July 2005. The patients selected
      for the study were categorized and analyzed on the basis of the presence or
      absence of POA. RESULTS: Overall, 166 (25.5%) patients developed POA. A
      multivariate logistic regression analysis identified that five significant
      factors--cirrhotic liver, high indocyanine green retention, portal hypertension,
      hypoalbuminemia, and extent of LR--were associated with the development of POA.
      The recurrence-free survival and overall survival of patients with POA were
      significantly lower than those of patients without POA. The 5-year recurrence
      free survival rates of patients with intractable POA over those of patients
      without POA were 31.7% versus 36.1%, and the corresponding 5-year overall
      survival rates were 17.4% versus 57.0%. The relative risk of mortality within 1
      year in patients with POA was 2.4 times (95% confidence interval, 1.76-3.27; p <
      0.001) higher than that in patients without POA. CONCLUSIONS: A nomogram for
      predicting the probability of POA after LR for HCC was constructed on the basis
      of the identified risk factors, which may be used for risk-stratifying patients
      who may or may not benefit from surgical resection. Because patients with POA
      after LR show a high incidence of HCC recurrence and mortality risk, those with
      intractable ascites should be considered for prompt liver transplantation.

PMID- 22131091
TI  - Should surgeons work in rural district hospitals in Africa?

PMID- 22131092
TI  - Re: Noninvasive positive pressure ventilation in the management of post
      thyroidectomy tracheomalacia.

PMID- 22131094
TI  - Preoperative 18F-FDG uptake is strongly correlated with malignancy, Weiss score,
      and molecular markers of aggressiveness in adrenal cortical tumors.
AB  - BACKGROUND: Adrenal incidentaloma are frequent in the general population. It can
      be difficult to diagnose adrenocortical carcinomas among them, even with the
      progress of imaging techniques. We studied the results of PET-FDG in the
      diagnosis of such tumours. METHODS: We studied patients referred to the
      Department of Endocrine Surgery at La Timone Hospital, Marseilles, France,
      between June 2006 and October 2010 for adrenal tumours. All patients underwent a
      complete work-up (biological tests and imagery), completed with PET-FDG. We
      compared the results of PET-FDG and molecular analysis with Weiss score and
      clinical follow-up. We calculated correlations with the Pearson test. RESULTS: A
      total of 51 patients were studied. We found that PET-FDG had a sensitivity of 95%
      and specificity of 97% for the diagnosis of adrenocortical carcinoma. The
      correlation between PET-FDG and Weiss score was 77% (P <= 0.0001). Molecular
      analyses were correlated as well with Weiss score and malignancy (P < 0.05).
      CONCLUSIONS: The nature of atypical adrenal masses can be difficult to define
      during preoperative investigations. For undetermined tumours smaller than 6 cm,
      characterization with PET-FDG can be one more diagnostic argument pointing to
      malignancy. It could potentially change the therapeutic strategy and surgical
      management. In our experience, molecular analyses are available after surgery and
      have less impact on the therapeutic strategy than PET-FDG. Preoperative PET-FDG
      can be an asset in the management of adrenal incidentaloma and adrenocortical
      carcinoma.

PMID- 22131095
TI  - Respiration-rate estimation of a moving target using impulse-based ultra wideband
      radars.
AB  - Recently, Ultra-wide band signals have become attractive for their particular
      advantage of having high spatial resolution and good penetration ability which
      makes them suitable in medical applications. One of these applications is
      wireless detection of heart rate and respiration rate. Two hypothesis of static
      environment and fixed patient are considered in the method presented in previous
      literatures which are not valid for long term monitoring of ambulant patients. In
      this article, a new method to detect the respiration rate of a moving target is
      presented. The first algorithm is applied to the simulated and experimental data
      for detecting respiration rate of a fixed target. Then, the second algorithm is
      developed to detect respiration rate of a moving target. The proposed algorithm
      uses correlation for body movement cancellation, and then detects the respiration
      rate based on energy in frequency domain. The results of algorithm prove an
      accuracy of 98.4 and 97% in simulated and experimental data, respectively.

PMID- 22131096
TI  - Mifepristone-inducible caspase-1 expression in mouse embryonic stem cells
      eliminates tumor formation but spares differentiated cells in vitro and in vivo.
AB  - Embryonic stem cell (ESC)-based therapy is a promising treatment for
      neurodegenerative diseases. But there is always a risk of tumor formation that is
      due to contamination of undifferentiated ESCs. To reduce the risk and improve ESC
      based therapy, we have established a novel strategy by which we can selectively
      eliminate tumor cells derived from undifferentiated ESCs but spare differentiated
      cells. In this study, we generated a caspase-1-ESC line transfected with a
      mifepristone-regulated caspase-1 expression system. Mifepristone induced caspase
      1 overexpression both in differentiated and undifferentiated caspase-1-ESCs. All
      the undifferentiated caspase-1-ESCs were induced to death after mifepristone
      treatment. Tumors derived from undifferentiated caspase-1-ESCs were eliminated
      following 3 weeks of mifepristone treatment in vivo. However, differentiated
      caspase-1-ESCs survived well under the condition of mifepristone-induced caspase
      1 overexpression. To examine in vivo the impact of mifepristone-induced caspase-1
      activation on grafted cells, we transplanted wild-type ESCs or caspase-1-ESCs
      into nude mice brains. After 8 weeks of mifepristone treatment, we could not
      detect any tumor cells in the caspase-1-ESC grafts in the brains of mice.
      However, we found that donor dopamine neurons survived in the recipient brains.
      These data demonstrate that mifepristone-induced caspase-1 overexpression in ESCs
      can eliminate the potential tumor formation meanwhile spares the differentiated
      cells in the host brains. These results suggest that this novel ESC-based therapy
      can be used in Parkinson's disease and other related disorders without the risk
      of tumor formation.

PMID- 22131101
TI  - Pharmacokinetics, tolerability, and preliminary efficacy of paquinimod (ABR
      215757), a new quinoline-3-carboxamide derivative: studies in lupus-prone mice
      and a multicenter, randomized, double-blind, placebo-controlled, repeat-dose,
      dose-ranging study in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To assess the efficacy of paquinimod, a new immunomodulatory small
      molecule, in a murine lupus model, and to evaluate its pharmacokinetics and
      tolerability in systemic lupus erythematosus (SLE) patients at doses predicted to
      be efficacious and safe and determine the maximum tolerated dose. METHODS: The
      efficacy of paquinimod was studied in lupus-prone MRL-lpr/lpr mice and compared
      with that of established SLE treatments. Dose-response data and pharmacokinetic
      data were used to calculate effective and safe clinical doses of paquinimod. The
      pharmacokinetics and tolerability of paquinimod were evaluated in a phase Ib
      double-blind, placebo controlled, dose-ranging study in which cohorts of SLE
      patients received daily oral treatment for 12 weeks. RESULTS: Paquinimod
      treatment resulted in disease inhibition in MRL-lpr/lpr mice, comparable to that
      obtained with prednisolone and mycophenolate mofetil; prominent effects on
      disease manifestations and serologic markers and a steroid-sparing effect were
      observed. In patients with SLE, the pharmacokinetic properties of paquinimod were
      linear and well suitable for once-daily oral treatment. The majority of the
      adverse events (AEs) were mild or moderate, and transient. The most frequent AEs
      were arthralgia and myalgia, reported with the highest dose levels of paquinimod
      (4.5 mg/day and 6.0 mg/day). At the 4.5 mg/day dose level and higher, some AEs of
      severe intensity and serious adverse events were reported. CONCLUSION: Paquinimod
      effectively inhibited disease and had a steroid-sparing effect in experimental
      lupus. Results from preclinical models together with pharmacokinetic data were
      successfully translated into a safe clinical dose range, and doses of up to 3.0
      mg/day were well tolerated in the SLE patients. Taken together, the promising
      combined data from a murine model and human SLE support the future clinical
      development of paquinimod.

PMID- 22131102
TI  - Structure and dynamics of triazole-linked DNA: biocompatibility explained.

PMID- 22131103
TI  - Scleroderma mimics.
AB  - Scleroderma is a rare systemic autoimmune disease with multiple organ
      manifestations, including skin fibrosis. The groups of disorders classified as
      scleroderma mimics share the common thread of skin thickening but are otherwise
      quite incongruous in terms of underlying disease process and other organ
      involvement. This article reviews the clinical presentation, etiology, and
      treatment options available for scleroderma mimics, including morphea,
      scleredema, diabetic cheiroarthropathy, scleromyxedema, nephrogenic systemic
      fibrosis, and eosinophilic fasciitis. Through greater understanding of these
      diseases and the associated extradermal implications, we hope to facilitate
      recognition of scleroderma and its mimics.

PMID- 22131104
TI  - Ethanol production from alkali-treated rice straw via simultaneous
      saccharification and fermentation using newly isolated thermotolerant Pichia
      kudriavzevii HOP-1.
AB  - In this study, simultaneous saccharification and fermentation (SSF) was employed
      to produce ethanol from 1% sodium hydroxide-treated rice straw in a
      thermostatically controlled glass reactor using 20 FPU gds-1 cellulase, 50 IU gds
      1 beta-glucosidase, 15 IU gds-1 pectinase and a newly isolated thermotolerant
      Pichia kudriavzevii HOP-1 strain. Scanning electron micrograph images showed that
      the size of the P. kudriavzevii cells ranged from 2.48 to 6.93 MUm in diameter
      while the shape of the cells varied from oval, ellipsoidal to elongate. Pichia
      kudriavzevii cells showed extensive pseudohyphae formation after 5 days of growth
      and could assimilate sugars like glucose, sucrose, galactose, fructose, and
      mannose but the cells could not assimilate xylose, arabinose, cellobiose,
      raffinose, or trehalose. In addition, the yeast cells could tolerate up to 40%
      glucose and 5% NaCl concentrations but their growth was inhibited at 1% acetic
      acid and 0.01% cyclohexamide concentrations. Pichia kudriavzevii produced about
      35 and 200% more ethanol than the conventional Saccharomyces cerevisiae cells at
      40 and 45 degrees C, respectively. About 94% glucan in alkali-treated rice straw
      was converted to glucose through enzymatic hydrolysis within 36 h. Ethanol
      concentration of 24.25 g l-1 corresponding to 82% theoretical yield on glucan
      basis and ethanol productivity of 1.10 g l-1 h-1 achieved using P. kudriavzevii
      during SSF hold promise for scale-up studies. An insignificant amount of glycerol
      and no xylitol was produced during SSF. To the best of our knowledge, this is the
      first study reporting ethanol production from any lignocellulosic biomass using
      P. kudriavzevii.

PMID- 22131105
TI  - Beliefs and personality disorders: an overview of the personality beliefs
      questionnaire.
AB  - OBJECTIVE: This article presents an overview of the Personality Beliefs
      Questionnaire (PBQ)--a 126-item self-report measure of beliefs associated with 10
      personality disorders. DESIGN: It consolidates the literature on the PBQ over the
      last 20 years to provide a summary of the psychometric status, revisions and
      applications of the PBQ scales. RESULTS: The PBQ scales are psychometrically
      reliable (alpha = 77-94, test-retest stability r=.57-.93) and discriminate
      between individuals with and without a specific personality disorder. Two
      revisions have been made to the measure: A 14-item subscale measuring beliefs
      central to borderline personality disorder has been identified, and a short form
      version of the PBQ has been validated. The PBQ has been used to measure cognitive
      mechanisms of treatment outcomes, and has been found to be sensitive to changes
      in beliefs. CONCLUSIONS: Given the proposed shift in the Diagnostic and
      Statistical Manual of Mental Disorders Fifth Edition (DSM-5) to a dimensional
      conceptualization of psychological components of personality dysfunction, the PBQ
      is likely to remain relevant and useful for identifying such components in
      individuals with personality disorders.

PMID- 22131106
TI  - Near infrared spectroscopy for monitoring flap viability following breast
      reconstruction.
AB  - Free flap monitoring is essential to the early detection of compromise thereby
      increasing the chance of successful salvage surgery. Many alternatives to
      classical clinical monitoring have been proposed. This study seeks to investigate
      a relatively new monitoring technology: near infrared spectroscopy (NIRS).
      Patients were recruited prospectively to the study from a single center. During
      the research period, 10 patients underwent reconstruction with a free deep
      inferior epigastric perforator flap (DIEP). Measurements of flap perfusion were
      taken using NIRS in the preoperative and intraoperative phases and
      postoperatively for 72 hours. NIRS showed characteristic changes in all cases
      which returned to theater for pedicle compromise. In these cases, NIRS identified
      pedicle compromise prior to clinical identification. There were no false
      positives. NIRS accurately identified all compromised flaps in our study. In most
      cases, there was an evidence of changes in oxygen saturation on NIRS prior to
      clinical observation. Further research, ideally double blind randomized control
      trials with large sample groups would be required to definitively establish NIRS
      as an ideal flap monitoring modality.

PMID- 22131107
TI  - A successful reconstruction using a frozen autograft and a pedicled latissimus
      dorsi flap after a S12345B shoulder girdle resection in a patient with
      osteosarcoma.
AB  - We present a case of high-grade osteosarcoma in the proximal humerus in an 8-year
      old boy. Massive tumor expansion required a S12345B shoulder girdle resection
      according to the system of the Musculoskeletal Tumor Society. After wide
      resection, only a small portion of the distal humerus and none of the rotator
      cuff muscles would be spared. Because the humeral portion would be too short to
      support the stem and the soft tissue would be insufficient to cover prosthetic
      components, we designed a composite reconstruction using a frozen autograft and a
      pedicled muscle flap. At 2 years postoperatively, our patient exhibited good
      adaptation and had acquired fine dexterity of the upper limb. To our knowledge,
      this is the first report regarding a successful composite reconstruction after a
      S12345B shoulder girdle resection.

PMID- 22131108
TI  - Tesaglitazar, a dual PPAR-alpha/gamma agonist, hamster carcinogenicity,
      investigative animal and clinical studies.
AB  - Tesaglitazar was developed as a dual peroxisome proliferator-activated receptor
      (PPARalpha/gamma). To support the clinical program, a hamster carcinogenicity
      study was performed. The only neoplastic findings possibly related to treatment
      with tesaglitazar were low incidences of hemangioma and hemangiosarcoma in the
      liver of male animals. A high-power, two-year investigative study with interim
      necropsies was performed to further elucidate these findings. Treatment with
      tesaglitazar resulted in changes typical for exaggerated PPARalpha pharmacology
      in rodents, such as hepatocellular hypertrophy and hepatocellular carcinoma, but
      not an increased frequency of hemangiosarcomas. At the highest dose level, there
      was an increased incidence of sinusoidal dilatation and hemangiomas. No increased
      endothelial cell (EC) proliferation was detected in vivo, which was confirmed by
      in vitro administration to ECs. Immunohistochemistry and gene expression analyses
      indicated increased cellular stress and vascular endothelial growth factor (VEGF)
      expression in the liver, which may have contributed to the sinusoidal dilatation.
      A two-fold increase in the level of circulating VEGF was detected in the hamster
      at all dose levels, whereas no effect on VEGF was observed in patients treated
      with tesaglitazar. In conclusion, investigations have demonstrated that
      tesaglitazar does not produce hemangiosarcomas in hamster despite a slight effect
      on vascular morphology in the liver.

PMID- 22131109
TI  - Embryotoxicity assessment of developmental neurotoxicants using a neuronal
      endpoint in the embryonic stem cell test.
AB  - The embryonic stem cell test (EST) is a validated in vitro embryotoxicity test;
      however, as the inhibition of cardiac differentiation alone is used as a
      differentiation endpoint in the EST, it may not be a useful test to screen
      embryotoxic chemicals that affect the differentiation of noncardiac tissues.
      Previously, methylmercury (MeHg), cadmium and arsenic compounds, which are heavy
      metals that induce developmental neurotoxicity in vivo, were misclassified as
      nonembryotoxic with the EST. The aim of this study was to improve the EST to
      correctly screen such developmental neurotoxicants. We developed a neuronal
      endpoint (Tuj-1 ID50) using flow cytometry analysis of Tuj-1-positive cells to
      screen developmental neurotoxicants (MeHg, valproic acid, sodium arsenate and
      sodium arsenite) correctly using an adherent monoculture differentiation method.
      Using Tuj-1 ID50 in the EST instead of cardiac ID50, all of the tested chemicals
      were classified as embryotoxic, while the negative controls were correctly
      classified as nonembryotoxic. To support the validity of Tuj-1 ID50) , we
      compared the results from two experimenters who independently tested MeHg using
      our modified EST. An additional neuronal endpoint (MAP2 ID50), obtained by
      analyzing the relative quantity of MAP2 mRNA, was used to classify the same
      chemicals. There were no significant differences in the three endpoint values of
      the two experimenters or in the classification results, except for isoniazid. In
      conclusion, our results indicate that Tuj-1 ID50 can be used as a surrogate
      endpoint of the traditional EST to screen developmental neurotoxicants correctly
      and it can also be applied to other chemicals.

PMID- 22131110
TI  - Review of 20 years of HPV research in Slovenia.
AB  - BACKGROUND: Human papillomaviruses (HPV), remarkably diverse DNA viruses
      etiologically linked with various benign and malignant neoplastic lesions of
      mucosal and skin epithelium have been the subject of intensive research for the
      last 30 years worldwide. OBJECTIVE: Briefly to review 20 years of HPV research in
      Slovenia by analyzing the articles published in journals indexed in peer-reviewed
      databases Medline/Pubmed, Science Citation Index/Web of Science, Embase and
      PsycINFO. METHODS AND RESULTS: Up until October 2011, Slovenian researchers
      published 73 articles in journals indexed in peer-reviewed databases, which can
      be divided into 15 categories: detection of HPV in archival clinical specimens,
      development of novel HPV tests, evaluation of various commercial tests for the
      detection of high- and low-risk alpha-HPV, HPV and anogenital tumours, HPV
      testing in routine gynecological practice, HPV and laryngeal benign tumours, HPV
      and laryngeal epithelial hyperplastic lesions and laryngeal cancer, HPV and
      tumors in oral cavity, HPV and esophageal benign and malignant tumors, HPV and
      inverted papillomas, genomic diversity of selected HPV types, hair follicles as
      an important endogenous reservoir of HPV, identification and characterization of
      novel HPV types, HPV vaccination and HPV basic research. Until October 2011,
      Slovenian HPV papers received 473 citations (self-citation excluded) and their
      Hirsch index is currently h=13. CONCLUSION: In the last 20 years, Slovenian HPV
      researchers have been actively and successfully incorporated in the international
      HPV community and have contributed small but significant achievements in the
      field.

PMID- 22131112
TI  - Histopathology of cervical precursor lesions and cancer.
AB  - The most frequent types of cervical cancer are squamous-cell carcinoma and
      adenocarcinoma, which develop from the distinctive precursor lesions cervical
      intraepithelial neoplasia (CIN) / squamous intraepithelial lesion (SIL), and
      adenocarcinoma in situ (AIS), respectively. Their tumorigenesis is HPV-related.
      High-risk HPV (e.g., types 16 and 18) is integrated into the genome and leads to
      tumor progression. Cytological screening leads to detection of precursors and
      their mimics. P16 and Ki-67 immunohistochemistry assists in the histological
      differential diagnosis of precursors to reactive and metaplastic epithelium. For
      invasive cervical carcinoma, stage is the strongest prognostic factor. Per
      definition, microinvasive (pT1a1 / pT1a2) carcinoma is diagnosed histologically
      on cone biopsies and treated less radically. The distinction between
      adenocarcinomas of the cervix and endometrial adenocarcinomas is important and
      can be supported by immunohistochemistry (e.g., ER, p16, CEA, and vimentin) and
      HPV in-situ hybridization. The rarer adenoid-basal and neuroendocrine carcinomas
      are less frequently HPV-related.

PMID- 22131111
TI  - Classification and nomenclature system for human Alphapapillomavirus variants:
      general features, nucleotide landmarks and assignment of HPV6 and HPV11 isolates
      to variant lineages.
AB  - BACKGROUND: Papillomaviruses constitute a family of viruses that can be
      classified into genera, species and types based on their viral genome
      heterogeneity. Currently circulating infectious human Alphapapillomaviruses
      (alpha-PVs) constitute a set of viral genomes that have evolved from archaic
      times and display features of host co-speciation. Viral variants are more
      recently evolved genomes that require a standardized classification and
      nomenclature. OBJECTIVES: To describe a system for the classification and
      nomenclature of HPV viral variants and provide landmarks for the numbering of
      nucleotide positions. METHODS: The complete 8 kb genomes of the alpha-9 species
      group and HPV6 and 11 types, collected from isolates throughout the world were
      obtained from published reports and GenBank. Complete genomes for each HPV type
      were aligned using the E1 start codon and sequence divergence was calculated by
      global and pairwise alignments using the MUSCLE program. Phylogenetic trees were
      constructed from the aligned sequences using a maximum likelihood method (RAxML).
      RESULTS: Pairwise comparisons of nucleotide differences between complete genomes
      of each type from alpha-9 HPV isolates (HPV16, 31, 33, 35, 52, 58 and 67)
      revealed a trimodal distribution. Maximum heterogeneity for variants within a
      type varied from 0.6%-2.3%. Nucleotide differences of approximately 1.0%-10.0%
      and 0.5%-1.0% of the complete genomes were used to define variant lineages and
      sublineages, respectively. Analysis of 43 HPV6 complete genomes indicated the
      presence of 2 variant lineages, whereas 32 HPV11 isolates were highly similar and
      clustered into 2 sublineages. A table was constructed of the human alpha-PV
      landmark nucleotide sequences for future reference and alignments. CONCLUSIONS: A
      proposed nomenclature system for viral variants and coordination of nucleotide
      positions will facilitate the comparison of variants across geographic regions
      and amongst different populations. In addition, this system will facilitate study
      of pathogenic, tissue tropism and functional differences amongst variant lineages
      of and polymorphisms within HPV variants.

PMID- 22131113
TI  - Prevalence of HPV 16 genomic variant carrying a 63 bp duplicated sequence within
      the E1 gene in Slovenian women.
AB  - High-risk HPV, particularly HPV-16, is etiologically associated with the
      development of cervical cancer and its precursor lesions - cervical
      intraepithelial neoplasia (CIN). However, most precancerous lesions will not
      progress to cancer. Numerous studies have shown that HPV-16 consists of several
      genomic variants, which differ in their association with cervical cancer, viral
      persistence and the frequency of recurrence of cervical disease. Recently, a
      novel, presumably less pathogenic, HPV-16 E6-T350G genomic variant has been
      identified, carrying a 63-bp in-frame insertion in the E1 gene. No data from
      Slovenian patients have so far been reported for this specific HPV-16 variant. In
      the present study, therefore, a total of 390 HPV-16 positive samples obtained
      from the same number of women with normal cytology, CIN I, CIN II, CIN III or
      cervical cancer, were analyzed. The HPV-16 E1 insert variant was detected using
      real-time PCR-amplification of a 146-210-bp fragment of the E1 gene and PCR
      sequencing of a 169-bp fragment of the E6 gene. The HPV-16 E1 insert variant was
      identified in 7/48 (14.6%), 1/21 (4.8%), 2/20 (10.0%), 9/131 (6.9%) and 12/170
      (7.1%) of women with normal cytology, CIN I, CIN II, CIN III and cervical cancer,
      respectively. All HPV-16 E1 insert variants with an amplifiable E6 gene belonged
      to the European HPV-16 E6-350G variant group. No statistically significant
      differences in the prevalence of HPV-16 E1 insert genomic variant in women
      presenting with normal cytology and those with the different stages of HPV-16
      induced disease were found.

PMID- 22131114
TI  - Distribution of HPV genotypes in Slovenian patients with anal carcinoma:
      preliminary results.
AB  - The aim of the present study was to obtain first data on the distribution of
      human papillomavirus (HPV) genotypes in patients with anal cancer (AC) in
      Slovenia. A total of 21 samples of AC (16 archival FFPE samples and 5 fresh
      frozen tissue samples) collected from the same number of patients were analysed.
      All samples were tested for the presence of HPV DNA using a consensus GP5+/ GP6+
      PCR and HPV genotypes determined by the INNO LiPA HPV Genotyping Extra test,
      capable of recognizing 28 different alfa-HPV genotypes. All 21 AC samples were
      HPV DNA positive. The most frequent HPV genotype, found in 19/21 AC samples, was
      HPV-16. Only low-risk HPV-6 was detected in one sample and infection with high
      risk HPV-52 and low-risk HPV-61 was identified in one sample. Prophylactic HPV
      vaccination with currently available vaccines could potentially prevent the great
      majority of anal cancers in Slovenia.

PMID- 22131115
TI  - Cutaneous manifestations of human papillomaviruses: a review.
AB  - Human papillomaviruses (HPVs) are small DNA viruses of the papovavirus family,
      with more than 100 types already described. Their importance in human disease
      cannot be overemphasized because these agents are among the most common pathogens
      in cutaneous infectious diseases and are very important in a subset of
      predominantly, but not exclusively, genital squamous-cell carcinomas. HPVs can be
      associated with a variety of cutaneous as well as mucosal manifestations. Some
      types of HPVs are associated with increased risk of epithelial malignancies;
      these have been divided into low-risk and high-risk types based on their
      oncogenic potential. Clinical and histological features of HPV infection vary
      according to individual susceptibility (e.g., immunosuppressed patients), site of
      involvement, and type of HPV implicated. The histological features of HPV
      infection are very easy to identify on sections stained with hematoxylin and
      eosin. However, many findings usually associated with HPV infection are entirely
      non-specific. Additional current diagnostic methods for identification of HPV in
      tissues include techniques based on the detection of viral DNA; namely, in-situ
      hybridization and polymerase chain reaction (PCR). This article reviews the main
      clinical and histopathological cutaneous manifestations of HPV infection,
      including common warts, plantar warts, plane warts, condyloma acuminatum,
      Bowenoid papulosis, and epidermodysplasia verruciformis. Emphasis is placed on
      the clinical and histological features of these various manifestations, including
      a brief discussion about the routinely used laboratory methods for detecting HPV
      in tissues.

PMID- 22131116
TI  - Genomic distribution of beta papillomaviruses in single eyebrow hair samples and
      pools of eyebrow hair samples.
AB  - Human beta papillomaviruses (beta-HPVs) are frequently detected in hairs and the
      majority of people are infected with multiple beta-HPV genotypes. This study was
      conducted to investigate for the first time the distribution of beta-HPV
      genotypes in single hair specimens and to estimate the contribution of a single
      hair to the beta-HPV profile obtained from a specimen made of multiple hairs
      pooled together. A total of 85 eyebrow hair specimens, representing 64 single
      hairs and 21 pools of hairs, obtained from 21 immunocompetent individuals, were
      tested using a reverse-line blot-based beta-HPV genotyping assay that allows
      identification of 25 different beta-HPVs. Overall, beta-HPV DNA was detected in
      82/84 (97.6%) samples. The great majority of hair pools (19/21; 90.5%) contained
      multiple beta-HPVs, the mean number of identified beta-HPV genotypes per hair
      pool was 5.2 (ranging from 1 to 12). In individual hairs, the great majority of
      individual hairs (43/63; 68.3%) contained multiple beta-HPVs, the mean number of
      identified beta-HPV genotypes was 4 (ranging from 1 to 12). Overall, HPV-23 was
      the most prevalent genotype, followed by HPV-24 and HPV-38. A comparison of beta
      HPV genotype distribution in pooled hair specimens and in at least one individual
      hair within a single patient revealed that 5/20 patients had a complete match
      between the number and profile of identified genotypes, 2/20 patients had the
      same/similar number of HPV genotypes but different genotype profile, 9/20
      patients had more HPV genotypes identified in pools than in the majority of
      individual hairs and 4/20 patients had at least one individual hair with more HPV
      genotypes identified than in the corresponding pool. Our results suggest that
      beta-HPVs are unevenly distributed over the eyebrows and even pools made of
      several hairs do not necessarily provide information on the whole spectrum of HPV
      genotypes present in eyebrows.

PMID- 22131117
TI  - Carcinoma of the head and neck in the HPV era.
AB  - This review encompasses the most salient advances in the understanding of the
      biopathology of head and neck squamous-cell carcinoma (HNSCC) accomplished over
      the last decade, emphasizing the significant role played by high-risk HPV
      genotypes. This has led to a new and meaningful subdivision of conventional HNSCC
      in two main prognostic and therapeutic groups: 1) keratinizing HNSCC, mainly
      occurring in elderly men that are heavy smokers and drinkers, TP53 mutated and/or
      p53-positive, HPV16-negative, being associated with an aggressive course; and 2)
      non-keratinizing HNSCC, occurring in younger men between 40 and 60 years that are
      non-smokers and non-drinkers, HPV16- positive, p16-positive, and p53- negative,
      being associated with improved prognosis. The main risk factors are number of
      sexual partners, oral-genital sex, oral-anal sex, and marijuana use. Among the
      unusual variants of HNSCC, papillary and lymphoepithelial-like are mostly related
      to HPV-16 infection, whereas the spindle and acantholytic types are mainly
      associated with tobacco and alcohol. The basaloid, adenosquamous, and verrucous
      variants may be related to both types of risk factors. Spindle cell carcinoma has
      been shown to be a prototype of epithelial mesenchymal transition. The hallmark
      of the novel and aggressive entity "undifferentiated midline carcinoma" is the
      rearrangement of the Nuclear Protein in Testis (NUT) gene at t[15; 19]. In the
      HPV era we are proposing the Ljubljana Classification (LC) as the recommended
      system for grading precursor lesions in heavy cigarette smokers and alcohol
      drinkers and the dysplasia and SIN systems for grading intraepithelial precursor
      lesions related to the increasingly detected epidemic of HNSCC associated with
      high-risk HPV infections.

PMID- 22131118
TI  - Adjuvant therapy for laryngeal papillomatosis.
AB  - Respiratory papillomatosis affects the larynx in most cases. It is a relatively
      rare disease, with potentially devastating consequences for the patient. Many
      studies have proven the viral etiology of the disease. Surgery is the most
      successful mode of treatment. Adjuvant therapy is used in cases of aggressive
      disease. The most successful adjuvant drugs are interferon, various virostatics
      (e.g., acyclovir, valacyclovir, and cidofovir) and indole-3-carbinol. Vaccination
      with a quadrivalent vaccine against HPV will probably decrease the incidence of
      respiratory papillomatosis or help in the treatment of the disease in the future.
      The results of adjuvant therapy of laryngeal papillomatosis at the University
      Department of ORL & HNS in Ljubljana are comparable to the results in other
      centers around the world.

PMID- 22131119
TI  - Reduction of cerebellar grey matter in Crus I and II in schizophrenia.
AB  - Structural deficiencies within the cerebellum have been associated with
      schizophrenia. Whereas several region-of-interest-based studies have shown
      deviations in cerebellar volume, meta-analyses on conventional whole-brain voxel
      based morphometry (VBM) studies do not implicate abnormalities in the cerebellum.
      Since this discrepancy could be due to methodological problems of VBM, we used a
      cerebellum-optimized VBM procedure. We acquired high-resolution MRI scans from 29
      schizophrenia patients and 45 healthy controls and used a VBM approach utilizing
      the Spatially Unbiased Infratentorial toolbox (Diedrichsen in Neuroimage 33:127
      138, 2006). Relative to healthy controls, schizophrenia patients showed
      reductions of grey matter volume in the left cerebellum Crus I/II that were
      correlated with thought disorder (p < 0.05; one-sided) and performance in the
      Trail-making test B (p < 0.01). No cerebellar group differences were detected
      employing conventional whole-brain VBM. The results derived from the cerebellum
      analysis provide evidence for distinct grey matter deficits in schizophrenia
      located in Crus I/II. The association of this area with thought disorder and
      Trail-making performance supports the previously suggested role of the cerebellum
      in coordination of mental processes including disordered thought in
      schizophrenia. The failure of conventional VBM to detect such effects suggests
      that previous studies might have underestimated the importance of cerebellar
      structural deficits in schizophrenia.

PMID- 22131120
TI  - The "SAFARI" technique using retrograde access via peroneal artery access.
AB  - The "SAFARI" technique or subintimal arterial flossing with antegrade-retrograde
      intervention is a method for recanalisation of chronic total occlusions (CTOs)
      when subintimal angioplasty fails. Retrograde access is usually obtained via the
      popliteal, distal anterior tibial artery (ATA)/dorsalis pedis (DP), or distal
      posterior tibial artery (PTA). Distal access via the peroneal artery has not been
      described and has a risk of continued bleeding, leading to compartment syndrome
      due to its deep location. We describe our experience in two patients with
      retrograde access via the peroneal artery and the use of balloon-assisted
      hemostasis for these retrograde punctures. This approach may potentially give
      more options for endovascular interventions in lower limb CTOs.

PMID- 22131121
TI  - Endovascular treatment of a renal arteriovenous malformation with Onyx.

PMID- 22131122
TI  - Percutaneous CT-guided treatment of osteochondritis dissecans of the sacroiliac
      joint.
AB  - Osteochondritis dissecans (OCD) is a joint disorder that affects the articular
      cartilage and subchondral bone, most commonly at the knee. OCD of the sacroiliac
      joint is extremely rare. Management of OCD remains controversial, and surgery is
      often needed, especially when conservative treatment fails. We present a rare
      case of OCD involving the left sacroiliac joint successfully treated by
      percutaneous computed tomography-guided retrograde drilling and debridement.

PMID- 22131123
TI  - Impact of heterozygous c.657-661del, p.I171V and p.R215W mutations in NBN on
      nibrin functions.
AB  - Nibrin, product of the NBN gene, together with MRE11 and RAD50 is involved in DNA
      double-strand breaks (DSBs) sensing and repair, induction of apoptosis and cell
      cycle control. Biallelic NBN mutations cause the Nijmegen breakage syndrome, a
      chromosomal instability disorder characterised by, among other things,
      radiosensitivity, immunodeficiency and an increased cancer risk. Several studies
      have shown an association of heterozygous c.657-661del, p.I171V and p.R215W
      mutations in the NBN gene with a variety of malignancies but the data are
      controversial. Little is known, however, whether and to what extent do these
      mutations in heterozygous state affect nibrin functions. We examined frequency of
      chromatid breaks, DSB repair, defects in S-phase checkpoint and radiosensitivity
      in X-ray-irradiated cells from control individuals, NBS patients and heterozygous
      carriers of the c.657-661del, p.I171V and p.R215W mutations. While cells
      homozygous for c.657-661del displayed a significantly increased number of
      chromatid breaks and residual gamma-H2AX foci, as well as abrogation of the intra
      S-phase checkpoint following irradiation, which resulted in increased
      radiosensitivity, cells with heterozygous c.657-661del, p.I171V and p.R215W
      mutations behaved similarly to control cells. Significant differences in the
      frequency of spontaneous and ionising radiation-induced chromatid breaks and the
      level of persistent gamma-H2AX foci were observed when comparing control and
      mutant cells heterozygous for c.657-661del. However, it is still possible that
      heterozygous NBN mutations may contribute to cancer development.

PMID- 22131124
TI  - Chromosome 11q13.3 variant modifies renal cell cancer risk in a Chinese
      population.
AB  - A recent genome-wide association study of renal cell carcinoma (RCC) in European
      population has identified genetic variants in the regions of 2p21 (rs7579899),
      11q13.3 (rs7105934) and 12q24.31 (rs4765623) conferred susceptibility to RCC. In
      our study, we assessed whether these polymorphisms are also associated with RCC
      risk in a Chinese population. We genotyped these polymorphisms using TaqMan
      method and assessed their associations with RCC risk in a case-control study of
      710 patients with histologically confirmed RCC and 760 cancer-free controls.
      Normal renal tissues adjacent to tumors were used to evaluate the functional
      consequences of these polymorphisms. We found that rs7105934 was significantly
      associated with reduced RCC risk [adjusted odds ratio (OR) = 0.67, 95% confidence
      intervals (CIs) = 0.47-0.95, GA+AA versus GG], particularly among subgroups of
      normal-weight individuals (OR = 0.51, 95%CI = 0.29-0.88), never-smokers (OR =
      0.53, 95%CI = 0.33-0.85) and non-drinkers (OR = 0.57, 95%CI = 0.370.87).
      Furthermore, the rs7105934 GA genotype was associated with lower levels of CCND1
      mRNA compared with GG genotype, although this association was only marginally
      significant (P = 0.055). No significant association between rs7579899 or
      rs7105934 and RCC risk was observed. Our results suggest that rs7105934 on
      11q13.3 may confer susceptibility to RCC in our population. Large population
      based prospective and functional studies are required to validate the
      associations between these loci and RCC risk.

PMID- 22131125
TI  - Aldehyde dehydrogenase activity is a biomarker of primitive normal human mammary
      luminal cells.
AB  - Elevated aldehyde dehydrogenase (ALDH) expression/activity has been identified as
      an important biomarker of primitive cells in various normal and malignant human
      tissues. Here we examined the level and type of ALDH expression and activity in
      different subsets of phenotypically and functionally defined normal human mammary
      cells. We find that the most primitive human mammary stem and progenitor cell
      types with bilineage differentiation potential show low ALDH activity but undergo
      a marked, selective, and transient upregulation of ALDH activity at the point of
      commitment to the luminal lineage. This mirrors a corresponding change in
      transcripts and protein levels of ALDH1A3, an enzyme involved in retinoic acid
      synthesis and the most highly expressed ALDH gene in normal human mammary tissue.
      In contrast, ALDH1A1 is expressed at low levels in all mammary epithelial cells.
      These findings raise interesting questions about the reported association of ALDH
      activity with breast cancer stem cells and breast cancer prognosis.

PMID- 22131126
TI  - Does age or bilateral disease influence the value of hip arthroplasty?
AB  - BACKGROUND: Measuring value in medicine is an increasingly important issue as
      healthcare spending continues to rise and cost containment becomes even more
      important. However, value assessments can be affected by patient factors and
      comorbidities. QUESTIONS/PURPOSES: We therefore quantified the approximate value
      of total hip arthroplasty and determined if patient age and Charnley
      classification affected the EuroQol5D (EQ5D) after hip arthroplasty. METHODS:
      Using charge data and an institutional joint registry, we evaluated 1442 patients
      after hip arthroplasty. Using the Charnley case-mix index to define bilateral
      disease and age of 65 years to distinguish between elderly and young patients,
      statistical comparisons were made among all groups. We obtained subspecialty
      physician charges and hospital charges. RESULTS: Patients with both unilateral
      and bilateral disease in both age groups had improved EQ5D scores after total hip
      arthroplasty, and the average change in scores was 0.27. There was no difference
      in the change in utility scores when patients older than 65 years of age were
      compared with patients younger than 65 years or when patients with unilateral
      disease were compared with those with bilateral disease. The average cost per
      quality-adjusted life-year (QALY) gained was $9773/QALY. CONCLUSIONS: Our data
      suggest the value of total hip arthroplasty compares favorably with other medical
      and surgical interventions for other patient groups. No adjustments for patient
      age or disease status of the contralateral limb are necessary when reporting the
      value of total hip arthroplasty. LEVEL OF EVIDENCE: Level IV, economic and
      decision analyses study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 22131127
TI  - Is monocyte chemotactic protein 1 elevated in aseptic loosening of TKA? A pilot
      study.
AB  - BACKGROUND: Failure of TKA from aseptic loosening is a growing concern, as TKA is
      performed with increasing frequency. Loosening is multifactorial and may be
      associated with elevated inflammatory cytokines in addition to biomechanical
      failure. QUESTIONS/PURPOSES: We asked whether proinflammatory cytokines and
      chemokines are elevated in synovial fluid from patients undergoing revision
      surgery as compared to those with osteoarthritis (OA) or rheumatoid arthritis
      (RA). METHODS: We obtained synovial fluid samples from 20 patients: six with
      aseptic loosening of TKA (all with bone loss), 10 with primary OA, and four with
      RA. A panel of cytokines/chemokines was screened using a SearchLight((r)) Array
      (Pierce Biotechnology, Rockford, IL, USA) in one revision sample. Using these
      data, we assayed the synovial fluids for monocyte chemotactic protein 1 (MCP-1)
      by ELISA. RESULTS: We observed an increase in synovial MCP-1 levels in samples
      from patients planned for TKA revision compared to those with OA or RA. In
      patients undergoing revision arthroplasty, the mean (+/- SD) MCP-1 concentration
      was 21,233 +/- 18,966 pg/mL (range, 1550-50,657 pg/mL; n = 6). In patients with
      OA, the mean MCP-1 level was 3012 +/- 3321 pg/mL. In patients with RA, the mean
      MCP-1 concentration was 690 +/- 561 pg/mL. CONCLUSIONS: All patients undergoing
      revision TKA showed elevated concentrations of MCP-1 compared to patients with OA
      and RA, suggesting MCP-1 may serve as a potential marker or predictor of bone
      loss in patients undergoing revision surgery. CLINICAL RELEVANCE: MCP-1 may be a
      novel biomarker in patients showing early symptoms of aseptic loosening of TKA.

PMID- 22131128
TI  - Reduced bioavailability of tamoxifen and its metabolite 4-hydroxytamoxifen after
      oral administration with biochanin A (an isoflavone) in rats.
AB  - The aim of this study was to investigate the effect of biochanin A (BCA) on the
      pharmacokinetics of tamoxifen, a substrate of P-glycoprotein (P-gp) and
      cytochrome 3A (CYP3A), in female rats. The tamoxifen was administered orally (10
      mg/kg) without or with oral BCA (100 mg/kg) in female rats. As BCA is an
      inhibitor of CYP 3A and P-gp it was expected to increase the bioavailability of
      tamoxifen, a known substrate of CYP3A4/Pgp. Surprisingly, compared with the
      control group (treated with tamoxifen alone), BCA pretreated animals showed
      significantly (p < 0.05) decreased area under the plasma concentration-time curve
      from time zero to time infinity (AUC(0-infinity)) and peak tamoxifen
      concentrations (C(max)). Consequently, the relative bioavailability (RB%) of
      tamoxifen co-administered with BCA was remarkably decreased compared with the
      control group. The AUC(0-infinity) and C(max) of 4-hydroxytamoxifen in BCA
      pretreated rats were also significantly (p < 0.05) lower than those from the
      control group. However, there were no apparent changes in the metabolite ratio
      (MR; AUC(0-infinity) of 4-hydroxytamoxifen to tamoxifen) by co-administration of
      BCA. If the results of this study are further confirmed by clinical trials,
      tamoxifen dosages should be adjusted to avoid potential drug interaction when
      tamoxifen is used clinically in combination with BCA and BCA-containing dietary
      supplements.

PMID- 22131130
TI  - Association of coronary heart disease mortality with risk factors according to
      length of follow-up and serum cholesterol level in men: the Oslo Study cohort.
AB  - AIM: We aimed to clarify the strength of the association between conventional and
      metabolic risk factors to coronary heart disease (CHD) mortality across short,
      intermediate, and long periods of follow-up and whether the effects of risk
      factors are heterogeneous across serum cholesterol levels. METHODS: The Oslo
      Study prospective cohort of 14,846 men aged 40-49 years was followed from
      screening in 1972-73 until 2006, during which time 1655 subjects died of CHD.
      Multivariate-adjusted Cox proportional models compared hazard ratios (HRs) and
      95% confidence intervals (CIs) for CHD mortality across 0-12, 12-24, and 24-33
      years of follow-up. Interactions between risk factors and quartile level of total
      serum cholesterol were assessed. RESULTS: Total cholesterol, blood pressure, and
      cigarette smoking were associated with CHD mortality in multivariate analyses
      across all follow-up periods. Nonfasting triglyceride levels were associated with
      CHD in multivariate analyses (0-12 years, HR 1.12, 95% CI 1.00-1.25; 12-24 years,
      HR 1.13, 95% CI 1.04-1.23; 24-33 years, HR 1.09, 95% CI 1.00-1.19; 0-33 years, HR
      1.10, 95% CI 1.05-1.16). A metabolic risk factor score (based on blood pressure,
      triglycerides, body mass index, and glucose) retained predictivity across all
      periods. The relations between systolic blood pressure, triglycerides, and
      metabolic risk factor score to CHD were stronger in the lower than the upper
      quartiles of serum cholesterol (p < 0.001). CONCLUSIONS: Conventional risk
      factors and nonfasting triglycerides increased CHD mortality across all periods
      of follow-up. The association with metabolic variables was strongest in men with
      low total cholesterol levels supporting the idea that lowering cholesterol should
      be the primary target of primary prevention.

PMID- 22131129
TI  - Microswitch technology and contingent stimulation to promote adaptive engagement
      in persons with minimally conscious state: a case evaluation.
AB  - This study assessed whether a post-coma woman functioning at the lower end of the
      minimally conscious state would (a) develop adaptive responding through the use
      of microswitch technology and contingent stimulation, (b) consolidate and
      maintain her responding over time, and (c) show evidence of response-consequences
      awareness (learning and discrimination). The study involved an ABABB1CB1 sequence
      in which the A represented baseline phases, the B and B1 intervention phases, and
      the C a control phase with continuous stimulation. Results indicated that the
      woman developed adaptive responding and consolidated it over the intervention
      phases of the study. The woman also showed evidence of being aware of response
      consequences links. Potential implications and limitations of these findings are
      discussed.

PMID- 22131131
TI  - Trends in incidence and outcome of out-of-hospital cardiac arrest among people
      with validated myocardial infarction.
AB  - AIMS: To describe trends in incidence, outcome, and background characteristics
      among people who suffered an out-of-hospital cardiac arrest with validated
      myocardial infarction aetiology (OHCA-V). METHODS AND RESULTS: People from the
      northern Sweden MONICA myocardial registry (1989-2007) with OHCA-V (n = 2977)
      were divided in two age groups (25-64 and 65-74 years). Both those who were
      resuscitated outside hospital and those who died before resuscitation was started
      were included in the study. The younger age group was studied during 1989-2007
      and the older group during 2000-2007. The incidence of OHCA-V decreased in both
      the younger group (men p < 0.0001, women p = 0.04) and the older group (men p <
      0.0001, women p < 0.0007, respectively). The proportion with a history of
      ischaemic heart disease prior to the event decreased (p < 0.0001). The proportion
      of previous myocardial infarction decreased (p < 0.0001), diabetes mellitus
      increased (p = 0.001), coronary interventions increased (p < 0.0001), and
      survival after OHCA-V increased (p < 0.0001) in the younger group but not in the
      older group. Long-term survival after OHCA-V was better in the younger than in
      the older group (p = 0.026). CONCLUSION: The incidence of OHCA-V decreased in
      both sexes. The proportion surviving after OHCA-V was small but increased, and
      long-term survival (>= 28 days) was better in the younger age group. Primary
      preventive measures may explain most of the improvements. However, the effects of
      secondary preventive measures cannot be excluded.

PMID- 22131133
TI  - Network bursting using experimentally constrained single compartment CA3
      hippocampal neuron models with adaptation.
AB  - The hippocampus is a brain structure critical for memory functioning. Its network
      dynamics include several patterns such as sharp waves that are generated in the
      CA3 region. To understand how population outputs are generated, models need to
      consider aspects of network size, cellular and synaptic characteristics and
      context, which are necessarily 'balanced' in appropriate ways to produce
      particular outputs. Thick slice hippocampal preparations spontaneously produce
      sharp waves that are initiated in CA3 regions and depend on the right balance of
      glutamatergic activities. As a step toward developing network models that can
      explain important balances in the generation of hippocampal output, we develop
      models of CA3 pyramidal cells. Our models are single compartment in nature, use
      an Izhikevich-type structure and involve parameter values that are specifically
      designed to encompass CA3 intrinsic properties. Importantly, they incorporate
      spike frequency adaptation characteristics that are directly comparable to those
      measured experimentally. Excitatory networks using these model cells are able to
      produce bursting suggesting that the amount of spike frequency adaptation
      expressed in the biological cells is an essential contributor to network
      bursting, and as such, may be important for sharp wave generation. The network
      bursting mechanism is numerically dissected showing the critical balance between
      adaptation and excitatory drive. The compact nature of our models allows large
      network simulations to be efficiently computed. This, together with the linkage
      of our models to cellular characteristics, will allow us to develop an
      understanding of population output of CA3 hippocampus with direct biological
      comparisons.

PMID- 22131134
TI  - Chronic inhalation of biomass smoke is associated with DNA damage in airway
      cells: involvement of particulate pollutants and benzene.
AB  - This study examined whether indoor air pollution from biomass fuel burning
      induces DNA damage in airway cells. For this, sputum cells were collected from 56
      premenopausal rural women who cooked with biomass (wood, dung, crop residues) and
      49 age-matched controls who cooked with cleaner liquefied petroleum gas. The
      levels of particulate matters with diameters of less than 10 and 2.5 um (PM(10)
      and PM(2.5)) in indoor air were measured using a real-time aerosol monitor.
      Benzene exposure was monitored by measuring trans,trans-muconic acid (t,t-MA) in
      urine by HPLC-UV. DNA damage was examined by alkaline comet assay in sputum
      cells. Generation of reactive oxygen species (ROS) and level of superoxide
      dismutase (SOD) in sputum cells were measured by flow cytometry and
      spectrophotometry, respectively. Compared with controls, biomass users had 4
      times higher tail percentage DNA, 37% more comet tail length and 5 times more
      Olive tail moment (p < 0.001) in inflammatory and epithelial cells in sputum,
      suggesting extensive DNA damage. In addition, women who cooked with biomass had 6
      times higher levels of urinary t,t-MA and 2-fold higher levels of ROS generation
      concomitant with 28% depletion of SOD. Indoor air of biomass-using households had
      2-4 times more PM(10) and PM(2.5) than that of controls. After controlling
      potential confounders, positive association was found between DNA damage
      parameters, particulate pollution, urinary t,t-MA and ROS. Thus, long-term
      exposure to biomass smoke induces DNA damage in airway cells and the effect was
      probably mediated, at least in part, by oxidative stress generated by inhaled
      particulate matter and benzene.

PMID- 22131136
TI  - TRIM family: Pleiotropy and diversification through homomultimer and
      heteromultimer formation.
AB  - The TRIM family is composed of multidomain ubiquitin E3 ligases characterized by
      the presence of the N-terminal tripartite motif (RING, B-boxes, and coiled coil).
      TRIM proteins transfer the ubiquitin moiety to specific substrates but are also
      involved in ubiquitin-like modifications, in particular SUMOylation and
      ISGylation. The TRIM family members are involved in a plethora of biological and
      physiological processes and, when altered, are implicated in many pathological
      conditions. Growing evidence indicates the pleiotropic effect of several TRIM
      genes, each of which might be connected to very diverse cellular processes. As a
      way to reconcile a single family member with several functions, we propose that
      structural features, that is, their ability to homo- and hetero-di(multi)merize,
      can increase and diversify TRIM ubiquitin E3 ligase capability.

PMID- 22131135
TI  - MicroRNA-9 up-regulates E-cadherin through inhibition of NF-kappaB1-Snail1
      pathway in melanoma.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs that post-transcriptionally regulate
      gene expression. Hsa-miR-9 has been shown to have opposite functions in different
      tumour types; however, the underlying mechanism is unclear. Here we show that hsa
      miR-9 is down-regulated in metastatic melanomas compared to primary melanomas.
      Overexpression of miR-9 in melanoma cells resulted in significantly decreased
      cell proliferation and migratory capacity with decreased F-actin polymerization
      and down-regulation of multiple GTPases involved in cytoskeleton remodelling. miR
      9 overexpression induced significant down-regulation of Snail1 with a concomitant
      increase in E-cadherin expression. In contrast, knockdown of miR-9 increased
      Snail1 expression as well as melanoma cell proliferation and migration capacity.
      Mechanistically, miR-9 expression down-regulated NF-kappaB1 in melanoma and the
      effect was abolished by mutations in the putative miR-9 binding sites within the
      3'-untranslated region (UTR) of NF-kappaB1. Anti-miR-9 miRNA inhibitor also
      increased the expression of NF-kappaB1. The effects of miR-9 on Snail1 expression
      and melanoma cell proliferation and migration were rescued by overexpression of
      NF-kappaB1 in these cells. Furthermore, miR-9 overexpression resulted in
      significantly decreased melanoma growth and metastasis in vivo. In summary, miR-9
      inhibits melanoma proliferation and metastasis through down-regulation of the NF
      kappaB1-Snail1 pathway. This study finds a new mechanism that miR-9 utilizes to
      decrease E-cadherin expression and inhibit melanoma progression. The results
      suggest that function of microRNAs is context and tumour type-specific.

PMID- 22131151
TI  - Inability of human induced pluripotent stem cell-hematopoietic derivatives to
      downregulate microRNAs in vivo reveals a block in xenograft hematopoietic
      regeneration.
AB  - Hematopoietic stem cells (HSCs) can regenerate the entire hematopoietic system in
      vivo, providing the most relevant criteria to measure candidate HSCs derived from
      human embryonic stem cell (hESC) or induced pluripotent stem cell (hiPSC)
      sources. Here we show that, unlike primitive hematopoietic cells derived from
      hESCs, phenotypically identical cells derived from hiPSC are more permissive to
      graft the bone marrow of xenotransplantation recipients. Despite establishment of
      bone marrow graft, hiPSC-derived cells fail to demonstrate hematopoietic
      differentiation in vivo. However, once removed from recipient bone marrow, hiPSC
      derived grafts were capable of in vitro multilineage hematopoietic
      differentiation, indicating that xenograft imparts a restriction to in vivo
      hematopoietic progression. This failure to regenerate multilineage hematopoiesis
      in vivo was attributed to the inability to downregulate key microRNAs involved in
      hematopoiesis. Based on these analyses, our study indicates that hiPSCs provide a
      beneficial source of pluripotent stem cell-derived hematopoietic cells for
      transplantation compared with hESCs. Since use of the human-mouse xenograft
      models prevents detection of putative hiPSC-derived HSCs, we suggest that new
      preclinical models should be explored to fully evaluate cells generated from
      hiPSC sources.

PMID- 22131152
TI  - Histone deacetylase inhibitor potentiates chemotherapy-induced apoptosis through
      Bim upregulation in Burkitt's lymphoma cells.
AB  - PURPOSE: Although polychemotherapy regiments have improved clinical outcome for
      Burkitt's lymphoma (BL) patients, salvage treatment of patients with refractory
      disease remains very poor. Combined therapies protocols have been emerging to
      improve treatment strategies to circumvent responseless BL patients. We evaluate
      the cell death effect of histone deacetylase inhibitor (HDACI) combined with
      etoposide (VP-16) and cisplatin (CDDP) on BL cell lines. METHODS: 3-(4,5-Dimethyl
      thiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay was performed to assess
      drug toxicity. To establish the concentrations and time of incubation for the
      combined treatment, a kinetic analysis was performed for each drug on BL41 and
      Raji BL cell lines for 24, 48 and 72 h. Apoptosis was assessed by flow cytometry
      using Annexin V/propidium iodide (PI) and cleaved caspase 3 labeling assays.
      Caspase 9 activation and levels of Bcl-2 family proteins were analyzed by Western
      blot. RESULTS: The doses of NaB (1.0 mM), CDDP (1.0 and 2.5 MUM), and VP-16 (0.1
      and 0.3 MUM) after 24 h of incubation were chosen for the evaluation of combined
      therapy. The apoptotic effects on BL cell lines of NaB/VP-16 and NaB/CDDP were
      followed by upregulation of Bim protein (P < 0.05), activation of caspase-3 and
      caspase-9, followed by Mcl-1 downregulation (P < 0.05). However, Bim
      overexpression was not correlated with Bcl-2 inhibition (P > 0.05) and was
      accompanied by increase in Bax expression (P < 0.05). The combination effects of
      NaB/VP-16 and NaB/CDDP were found to be synergistic and additive, respectively,
      in both the cell lines. CONCLUSIONS: The study provides strong evidence for the
      synergistic effects of the association with HDCI and chemotherapy in BL cells.

PMID- 22131154
TI  - Lignans with anti-hepatitis B virus activities from Phyllanthus niruri L.
AB  - One new lignan, nirtetralin B, along with its two known stereoisomers were
      isolated from Phyllanthus niruri L. The structure of the new compound was
      determined by spectroscopy experiments and x-ray diffraction analysis. These
      lignans were assayed for anti-hepatitis B virus activities in vitro. Nirtetralin
      and nirtetralin A, B effectively suppressed the secretion of the HBV antigens in
      a dose-dependent manner with IC50 values for HBsAg of 9.5 uM (nirtetralin A),
      16.7 uM (nirtetralin B) and 97.2 uM (nirtetralin), IC50 values for HBeAg of 17.4
      uM (nirtetralin A), 69.3 uM (nirtetralin B) and 232.0 uM (nirtetralin),
      respectively.

PMID- 22131153
TI  - Regulatory T cells essential to prevent the loss of self-tolerance in murine
      models of erythrocyte-specific autoantibody responses.
AB  - The spontaneous appearance of anti-erythrocyte autoantibodies resulting in
      autoimmune hemolytic anemia described in NZB mice more than 40 years ago provided
      a model for the study of mechanisms behind the loss of self-tolerance. We
      developed an in vitro model of this anti-MRBC response in which CD8(+) suppressor
      T cells were shown to be a controlling element. CD8(+) T cells from young NZB
      mice co-cultured with spleen cells from old, actively autoimmune NZB mice
      suppressed the anti-MRBC responses of the old mice. Eliminating the CD8(+) cells
      from young NZB spleen cells or even from non-autoimmune BALB/c spleen cells prior
      to culture removed the controlling influence of these CD8(+) cells and allowed
      the development of anti-MRBC-secreting cells. This review will consider the role
      of the CD8(+) suppressive cells in the anti-self-erythrocyte model in light of
      insights provided by current 'regulatory T cell' literature.

PMID- 22131155
TI  - [Diagnosis and therapy of obstructive sleep apnea syndrome in children with
      premature craniosynostosis syndromes].
AB  - Sleep related breathing disorders are a common symptom in children with
      craniosynostosis syndromes, as upper airways may be narrowed by midfacial
      hypoplasia.To better characterize the sleep related apneas, 24 children with
      syndromal craniofacial dysplasia underwent 68 poly-somnographies. 9 patients had
      reexaminations after therapeutic procedures. 4 patients had severe obstructive
      sleep apnea syndrom (OSAS), 8 patients had moderate and 11 patients mild
      obstructive sleep apnea respectivly. Only one child had no obstructive sleep
      apnea. Children with Morbus Crouzon tended to have moderate to severe breathing
      disorders (9/14) whereas Apert patients mostly had no or light breathing
      disorders (6/7). Number of central apneas was increased as well. Sleep
      architecture was not significantly impaired. Apneas were more frequent during REM
      sleep. Nasal CPAP, BiPAP and adenotonsillectomy improved respiratory
      parameters.Pulse oxymetry can be used as a screening method because of the good
      correla-tion of oxygen desaturation index with severity of OSAS. Frequent
      examinations and, if necessary, adaptation of therapy is indicated as OSAS in 
      these children may be rapidly changing. We suggest a guideline for diagnostics
      and therapy.

PMID- 22131156
TI  - The impact of impaired mitochondrial function on retrograde signalling: a meta
      analysis of transcriptomic responses.
AB  - Mitochondria occupy a central position in cellular metabolism. Their protein
      complement must therefore be dynamically adjusted to the metabolic demands of the
      cell. As >95% of mitochondrial proteins are encoded by nuclear DNA, regulation of
      the mitochondrial proteome requires signals that sense the status of the
      organelle and communicate it back to the nucleus. This is referred to as
      retrograde signalling. Mitochondria are tightly integrated into the network of
      cellular processes, and the output of mitochondrial retrograde signalling
      therefore not only feeds back to the mitochondrion, but also regulates functions
      across the cell. A number of transcriptomic studies have assessed the role of
      retrograde signalling in plants. However, single studies of a specific
      mitochondrial dysfunction may also measure secondary effects in addition to the
      specific transcriptomic output of mitochondrial signals. To gain an improved
      understanding of the output and role of mitochondrial retrograde signalling, a
      meta-analysis of 11 transcriptomic data sets from different models of plant
      mitochondrial dysfunction was performed. Comparing microarray data from stable
      mutants and short-term chemical treatments revealed unique features and
      commonalities in the responses that are under mitochondrial retrograde control.
      In particular, a common regulation of transcripts of the following functional
      categories was observed: plant-pathogen interactions, protein biosynthesis, and
      light reactions of photosynthesis. The possibility of a novel mode of
      interorganellar signalling, in which the mitochondrion influences processes in
      the plastid and other parts of the cell, is discussed.

PMID- 22131157
TI  - Elevated cytokinin content in ipt transgenic creeping bentgrass promotes drought
      tolerance through regulating metabolite accumulation.
AB  - Increased endogenous plant cytokinin (CK) content through transformation with an
      adenine isopentyl transferase (ipt) gene has been associated with improved plant
      drought tolerance. The objective of this study is to determine metabolic changes
      associated with elevated CK production in ipt transgenic creeping bentgrass
      (Agrostis stolonifera L.) with improved drought tolerance. Null transformants
      (NTs) and plants transformed with ipt controlled by a stress- or senescence
      activated promoter (SAG12-ipt) were exposed to well-watered conditions or drought
      stress by withholding irrigation in an environmental growth chamber.
      Physiological analysis confirmed that the SAG12-ipt line (S41) had improved
      drought tolerance compared with the NT plants. Specific metabolite changes over
      the course of drought stress and differential accumulation of metabolites in
      SAG12-ipt plants compared with NT plants at the same level of leaf relative water
      content (47% RWC) were identified using gas chromatography-mass spectroscopy. The
      metabolite profiling analysis detected 45 metabolites differentially accumulated
      in response to ipt expression or drought stress, which included amino acids,
      carbohydrates, organic acids, and organic alcohols. The enhanced drought
      tolerance of SAG12-ipt plants was associated with the maintenance of accumulation
      of several metabolites, particularly amino acids (proline, gamma-aminobutyric
      acid, alanine, and glycine) carbohydrates (sucrose, fructose, maltose, and
      ribose), and organic acids that are mainly involved in the citric acid cycle. The
      accumulation of these metabolites could contribute to improved drought tolerance
      due to their roles in the stress response pathways such as stress signalling,
      osmotic adjustment, and respiration for energy production.

PMID- 22131158
TI  - The potential for underutilized crops to improve security of food production.
AB  - Staple crops face major challenges in the near future and a diversification away
      from over-reliance on staples will be important as part of the progress towards
      the goal of achieving security of food production. Underutilized or neglected
      crops species are often indigenous ancient crop species which are still used at
      some level within the local, national or even international communities, but have
      the potential to contribute further to the mix of food sources than they
      currently do. The most cost-effective and easily disseminated changes that can be
      made to a crop are changes to the genetics, as these are contained within the
      seed itself and, for many species, the seed is a pure breeding, self-replicating,
      resource. This article focuses on the potential of underutilized crops to
      contribute to food security and, in particular, whether genetics and breeding can
      overcome some of the constraints to the enhanced uptake of these species in the
      future. The focus here is on overview rather than detail and subsequent articles
      will examine the current evidence base.

PMID- 22131160
TI  - Evidence for functional interaction between brassinosteroids and cadmium response
      in Arabidopsis thaliana.
AB  - Plant hormones, in addition to regulating growth and development, are involved in
      biotic and abiotic stress responses. To investigate whether a hormone signalling
      pathway plays a role in the plant response to the heavy metal cadmium (Cd), gene
      expression data in response to eight hormone treatments were retrieved from the
      Genevestigator Arabidopsis thaliana database and compared with published
      microarray analysis performed on plants challenged with Cd. Across more than 3000
      Cd-regulated genes, statistical approaches and cluster analyses highlighted that
      gene expression in response to Cd and brassinosteroids (BR) showed a significant
      similarity. Of note, over 75% of the genes showing consistent (e.g. opposite)
      regulation upon BR and Brz (BR biosynthesis inhibitor) exposure exhibited a BR
      like response upon Cd exposure. This phenomenon was confirmed by qPCR analysis of
      the expression level of 10 BR-regulated genes in roots of Cd-treated wild-type
      (WT) plants. Although no change in BR content was observed in response to Cd in
      our experimental conditions, adding epibrassinolide (eBL, a synthetic
      brassinosteroid) to WT plants significantly enhanced Cd-induced root growth
      inhibition, highlighting a synergistic response between eBL and the metal. This
      effect was specific to this hormone treatment. On the other hand, dwarf1
      seedlings, showing a reduced BR level, exhibited decreased root growth inhibition
      in response to Cd compared with WT, reversed by the addition of eBL. Similar
      results were obtained on Brz-treated WT plants. These results argue in favour of
      an interaction between Cd and BR signalling that modulates plant sensitivity, and
      opens new perspectives to understand the plant response to Cd.

PMID- 22131161
TI  - Vipp1: a very important protein in plastids?!
AB  - As a key feature in oxygenic photosynthesis, thylakoid membranes play an
      essential role in the physiology of plants, algae, and cyanobacteria. Despite
      their importance in the process of oxygenic photosynthesis, their biogenesis has
      remained a mystery to the present day. A decade ago, vesicle-inducing protein in
      plastids 1 (Vipp1) was described to be involved in thylakoid membrane formation
      in chloroplasts and cyanobacteria. Most follow-up studies clearly linked Vipp1 to
      membranes and Vipp1 interactions as well as the defects observed after Vipp1
      depletion in chloroplasts and cyanobacteria indicate that Vipp1 directly binds to
      membranes, locally stabilizes bilayer structures, and thereby retains membrane
      integrity. Here current knowledge about the structure and function of Vipp1 is
      summarized with a special focus on its relationship to the bacterial phage shock
      protein A (PspA), as both proteins share a common origin and appear to have
      retained many similarities in structure and function.

PMID- 22131159
TI  - Efficient acclimation of the chloroplast antioxidant defence of Arabidopsis
      thaliana leaves in response to a 10- or 100-fold light increment and the possible
      involvement of retrograde signals.
AB  - Chloroplasts are equipped with a nuclear-encoded antioxidant defence system the
      components of which are usually expressed at high transcript and activity levels.
      To significantly challenge the chloroplast antioxidant system, Arabidopsis
      thaliana plants, acclimated to extremely low light slightly above the light
      compensation point or to normal growth chamber light, were moved to high light
      corresponding to a 100- and 10-fold light jump, for 6 h and 24 h in order to
      observe the responses of the water-water cycle at the transcript, protein, enzyme
      activity, and metabolite levels. The plants coped efficiently with the high light
      regime and the photoinhibition was fully reversible. Reactive oxygen species
      (ROS), glutathione and ascorbate levels as well as redox states, respectively,
      revealed no particular oxidative stress in low-light-acclimated plants
      transferred to 100-fold excess light. Strong regulation of the water-water cycle
      enzymes at the transcript level was only partly reflected at the protein and
      activity levels. In general, low light plants had higher stromal (sAPX) and
      thylakoid ascorbate peroxidase (tAPX), dehydroascorbate reductase (DHAR), and
      CuZn superoxide dismutase (CuZnSOD) protein contents than normal light-grown
      plants. Mutants defective in components relevant for retrograde signalling,
      namely stn7, ex1, tpt1, and a mutant expressing E .coli catalase in the
      chloroplast showed unaltered transcriptional responses of water-water cycle
      enzymes. These findings, together with the response of marker transcripts,
      indicate that abscisic acid is not involved and that the plastoquinone redox
      state and reactive oxygen species do not play a major role in regulating the
      transcriptional response at t=6 h, while other marker transcripts suggest a major
      role for reductive power, metabolites, and lipids as signals for the response of
      the water-water cycle.

PMID- 22131162
TI  - Pyrabactin, an ABA agonist, induced stomatal closure and changes in signalling
      components of guard cells in abaxial epidermis of Pisum sativum.
AB  - Pyrabactin, a synthetic agonist of abscisic acid (ABA), inhibits seed germination
      and hypocotyl growth and stimulates gene expression in a very similar way to ABA,
      implying the possible modulation of stomatal function by pyrabactin as well. The
      effect of pyrabactin on stomatal closure and secondary messengers was therefore
      studied in guard cells of Pisum sativum abaxial epidermis. Pyrabactin caused
      marked stomatal closure in a pattern similar to ABA. In addition, pyrabactin
      elevated the levels of reactive oxygen species (ROS), nitric oxide (NO), and
      cytoplasmic pH levels in guard cells, as indicated by the respective
      fluorophores. However, apyrabactin, an inactive analogue of ABA, did not affect
      either stomatal closure or the signalling components of guard cells. The effects
      of pyrabactin-induced changes were reversed by pharmalogical compounds that
      modulate ROS, NO or cytoplasmic pH levels, quite similar to ABA effects.
      Fusicoccin, a fungal toxin, could reverse the stomatal closure caused by
      pyrabactin, as well as that caused by ABA. Experiments on stomatal closure by
      varying concentrations of ABA, in the presence of fixed concentration of
      pyrabactin, and vice versa, revealed that the actions of ABA and pyrabactin were
      additive. Further kinetic analysis of data revealed that the apparent K(D) of ABA
      was increased almost 4-fold in the presence of ABA, suggesting that pyrabactin
      and ABA were competing with each other either at the same site or close to the
      active site. It is proposed that pyrabactin could be used to examine the ABA
      related signal-transduction components in stomatal guard cells as well as in
      other plant tissues. It is also suggested that pyrabactin can be used as an
      antitranspirant or as a priming agent for improving the drought tolerance of crop
      plants.

PMID- 22131163
TI  - FIA functions as an early signal component of abscisic acid signal cascade in
      Vicia faba guard cells.
AB  - An abscisic acid (ABA)-insensitive Vicia faba mutant, fia (fava bean impaired in
      ABA-induced stomatal closure) had previously been isolated. In this study, it was
      investigated how FIA functions in ABA signalling in guard cells of Vicia faba.
      Unlike ABA, methyl jasmonate (MeJA), H(2)O(2), and nitric oxide (NO) induced
      stomatal closure in the fia mutant. ABA did not induce production of either
      reactive oxygen species or NO in the mutant. Moreover, ABA did not suppress
      inward-rectifying K(+) (K(in)) currents or activate ABA-activated protein kinase
      (AAPK) in mutant guard cells. These results suggest that FIA functions as an
      early signal component upstream of AAPK activation in ABA signalling but does not
      function in MeJA signalling in guard cells of Vicia faba.

PMID- 22131164
TI  - Social stability and health: exploring multidimensional social disadvantage.
AB  - Social stability is an understudied construct in public health that offers a
      useful framework for understanding social disadvantage across multiple domains.
      This study investigated prevalence and patterns of cooccurrence among a
      hypothesized set of social stability characteristics (housing, residential
      transition, employment, income, incarceration, and partner relationship),
      evaluated the possibility of underlying subgroups of social stability, and
      investigated the association between social stability and health outcomes. Data
      were from comprehensive interviews with primarily African-American low income
      urban women and their female social network members (n = 635) in Baltimore.
      Analysis included exploratory statistics, latent class analysis, and latent class
      regression accounting for clustered data using Stata and Mplus software. Social
      stability characteristics cooccurred in predictable directions, but with
      heterogeneity. Respondents had an average of three stability characteristics
      (S.D.: 1.4). Latent class analysis identified two classes of social stability:
      low (25%) and high (75%), with the higher class less likely to experience each of
      the included indicators. In controlled models, higher social stability was
      significantly correlated with social network characteristics and neighborhood
      integration. Higher social stability was independently associated with reduced
      risk of chronic illness (AOR: 0.54, 95% C.I.: 0.31, 0.94), mental illness history
      (AOR: 0.24, 95% CI: 0.15, 0.39), and current depressive symptoms (AOR: 0.35, 95%
      C.I.: 0.22, 0.57). The current set of social stability characteristics appears to
      represent a single construct with identifiable underlying subgroups and
      associated health disparities. Findings suggest a need for comprehensive policies
      and programs that address structural determinants of cooccurring social
      disadvantage and help to mitigate the likely spiral effect of instability
      experiences.

PMID- 22131165
TI  - Conformational analysis by quantitative NOE measurements of the beta-proton pairs
      across individual disulfide bonds in proteins.
AB  - NOEs between the beta-protons of cysteine residues across disulfide bonds in
      proteins provide direct information on the connectivities and conformations of
      these important cross-links, which are otherwise difficult to investigate. With
      conventional [U-(13)C, (15)N]-proteins, however, fast spin diffusion processes
      mediated by strong dipolar interactions between geminal beta-protons prohibit the
      quantitative measurements and thus the analyses of long-range NOEs across
      disulfide bonds. We describe a robust approach for alleviating such difficulties,
      by using proteins selectively labeled with an equimolar mixture of (2R, 3S)-[beta
      (13)C; alpha,beta-(2)H(2)] Cys and (2R, 3R)-[beta-(13)C; alpha,beta-(2)H(2)] Cys,
      but otherwise fully deuterated. Since either one of the prochiral methylene
      protons, namely beta2 (proS) or beta3 (proR), is always replaced with a deuteron
      and no other protons remain in proteins prepared by this labeling scheme, all
      four of the expected NOEs for the beta-protons across disulfide bonds could be
      measured without any spin diffusion interference, even with long mixing times.
      Therefore, the NOEs for the beta2 and beta3 pairs across each of the disulfide
      bonds could be observed at high sensitivity, even though they are 25% of the
      theoretical maximum for each pair. With the NOE information, the disulfide bond
      connectivities can be unambiguously established for proteins with multiple
      disulfide bonds. In addition, the conformations around disulfide bonds, namely
      chi(2) and chi(3), can be determined based on the precise proton distances of the
      four beta-proton pairs, by quantitative measurements of the NOEs across the
      disulfide bonds. The feasibility of this method is demonstrated for bovine
      pancreatic trypsin inhibitor, which has three disulfide bonds.

PMID- 22131166
TI  - No jacket required--new fungal lineage defies dress code: recently described
      zoosporic fungi lack a cell wall during trophic phase.
AB  - Analyses of environmental DNAs have provided tantalizing evidence for "rozellida"
      or "cryptomycota", a clade of mostly undescribed and deeply diverging aquatic
      fungi. Here, we put cryptomycota into perspective through consideration of
      Rozella, the only clade member growing in culture. This is timely on account of
      the publication in Nature of the first images of uncultured cryptomycota from
      environmental filtrates, where molecular probes revealed non-motile cyst-like
      structures and motile spores, all lacking typical fungal chitinous cell walls.
      Current studies of Rozella can complement these fragmentary observations from
      environmental samples. Rozella has a fungal-specific chitin synthase and its
      resting sporangia have walls that appear to contain chitin. Cryptomycota,
      including Rozella, lack a cell wall when absorbing food but like some other
      fungi, they may have lost their "dinner jacket" through convergence. Rather than
      evolutionary intermediates, the cryptomycota may be strange, divergent fungi that
      evolved from an ancestor with a nearly complete suite of classical fungal
      specific characters.

PMID- 22131167
TI  - Role of oxidative stress in the pathogenesis of sickle cell disease.
AB  - Sickle cell disease (SCD) is a class of hemoglobinopathy in humans, which causes
      a disruption of the normal activities in different systems. Although this disease
      begins with the polymerization of red blood cells during its deoxygenating phase,
      it can erupt into a cascade of debilitating conditions such as ischemia
      reperfusion injury, inflammation, and painful vaso-occlusion crises. The purpose
      of this review is to discuss how these phenomena can result in the formation of
      oxidative stress as well as limit nitric oxide (NO) bioavailability and decrease
      antioxidant status. The cumulative effects of these traits cause an increase in
      other forms of reactive oxygen species (ROS), which in turn intensify the
      symptoms of SCD and generate a vicious circle. Finally, we will discuss
      antioxidant therapeutic strategies that limit ROS generation and subsequently
      increase NO bioavailability with respect to endothelial protection in SCD.

PMID- 22131168
TI  - Tanning behaviors and determinants of solarium use among indoor office workers in
      Queensland, Australia.
AB  - Using cross-sectional survey data from Brisbane, Australia, this study identifies
      prevalence and factors associated with indoor tanning in office workers. Over 12
      months, 72/2867 (2.5%) survey participants used solaria. Twenty-eight sunbed
      users (39%) tanned outdoors and used spray-tans and 42 (58%) reported burns after
      indoor tanning. Results from regression modelling suggests the strongest
      predictors of sunbed use were beliefs that tanning was safer indoors than
      outdoors (OR 6.1, 95%CI: 2.6-14.0) and engaging in outdoor tanning (OR 4.1,
      95%CI: 1.8-9.0). We recommend that health authorities promote health gains by
      reducing ultraviolet radiation exposure or substituting indoor tanning with a
      spray-on tan.

PMID- 22131169
TI  - Connexin 43 reverses malignant phenotypes of glioma stem cells by modulating E
      cadherin.
AB  - Malfunctioned gap junctional intercellular communication (GJIC) has been thought
      associated with malignant transformation of normal cells. However, the role of
      GJIC-related proteins such as connexins in sustaining the malignant behavior of
      cancer stem cells remains unclear. In this study, we obtained tumorspheres formed
      by glioma stem cells (GSCs) and adherent GSCs and then examined their GJIC. All
      GSCs showed reduced GJIC, and differentiated glioma cells had more gap junction
      like structures than GSCs. GSCs expressed very low level of connexins, Cx43 in
      particular, which are key components of gap junction. We observed
      hypermethylation in the promoter of gap junction protein alpha1, which encodes
      Cx43 in GSCs. Reconstitution of Cx43 in GSCs inhibited their capacity of self
      renewal, invasiveness, and tumorigenicity via influencing E-cadherin and its
      coding protein, which leads to changes in the expression of Wnt/beta-catenin
      targeting genes. Our results suggest that GSCs require the low expression of Cx43
      for maintaining their malignant phenotype, and upregulation of Cx43 might be a
      potential strategy for treatment of malignant glioma.

PMID- 22131170
TI  - Transient locked-in syndrome and basilar artery vasospasm.
AB  - BACKGROUND: Cerebral vasospasm is the main cause of neurological mortality and
      morbidity following subarachnoid hemorrhage. Basilar artery vasospasm (BAVS) is
      associated with a high morbidity and may have multiple clinical presentations.
      METHODS: We report the case of a 43 years-old man with BAVS presenting as a
      reversible locked-in syndrome (LIS) after stopping sedation. RESULTS: The
      symptoms were successfully managed by intra-arterial infusion of vasodilators and
      balloon angioplasty. Magnetic resonance imaging did not reveal any brainstem
      lesion 48 h after the complication, demonstrating a hemodynamic mechanism.
      CONCLUSION: LIS can reveal BAVS. Its diagnosis relies on clinical examination. In
      this case, rapid neuro-interventional treatment permitted reversal of symptoms.
      This could not have been possible under sedation.

PMID- 22131171
TI  - Protective effects of paeoniflorin against corticosterone-induced neurotoxicity
      in PC12 cells.
AB  - Neuroprotection has been proposed as one of the acting mechanisms of
      antidepressants. Paeoniflorin, a monoterpene glycoside, has been reported to
      display antidepressant-like effects in animal models of behavioural despair. The
      present study aimed to examine the protective effect of paeoniflorin treatment on
      corticosterone-induced neurotoxicity in cultured rat pheochromocytoma (PC12)
      cells. Paeoniflorin was shown to elevate cell viability, decrease levels of
      intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) in
      corticosterone-treated PC12 cells. Paeoniflorin also reversed the reduced nerve
      growth factor (NGF) mRNA level caused by corticosterone in PC12 cells. The
      results suggest that paeoniflorin exerts a neuroprotective effect on
      corticosterone-induced neurotoxicity in PC12 cells, at least in part, via the
      inhibition of oxidative stress and the up-regulation of NGF expression. This
      neuroprotective effect may be one of the action pathways that accounts for the in
      vivo antidepressant activity of paeoniflorin.

PMID- 22131172
TI  - [Ultrasound of foreign bodies in the head and neck. Cases compared with an in
      vitro model].
AB  - BACKGROUND: High resolution ultrasound is an accepted method in identification
      and classification of various head and neck alterations. Foreign bodies are a
      seldom encountered entity and are supposed to have a characteristic echogenicity.
      In literature there are numerous publications describing diagnosing foreign
      bodies in other specialities like gynaecology or surgery with ultrasound. The aim
      of the study was to examine these findings and to reproduce them in the head and
      neck area. MATERIALS AND METHODS: The study includes the retrospective analysis
      of 6 cases. 3 cases have been reconstructed in a cadaver dissection model and a
      selfmade gel model. The findings were compared to the clinical cases and
      interpreted. RESULTS: In ultrasound foreign bodies have characteristic reflexions
      and artefacts. The diagnosis foreign body could be made in every case. The
      foreign body could not only be identified but also precisely localized. The
      findings were reproducable in both the cadaver and gel model. CONCLUSION: High
      resolution ultrasound is a dynamic, 3-dimentional, inexpensive, portable and
      readily available imaging method, facilitating the identification of lesions in
      the superficial soft tissues. In the hands of an experienced operator ultrasound
      may be the first imaging modality to be used for detection of radiolucent foreign
      bodies in head and neck area.

PMID- 22131173
TI  - [Recurrent Infl ammation of the cheek and in the external auditory canal].

PMID- 22131174
TI  - [Epithesis for neck area - an adjuvant for the healing process?!].

PMID- 22131175
TI  - [The vocal rehabilitation with ESKA-Herrmann voice prosthesis. a report of a 10
      years' experience].
AB  - ESKA-Herrmann voice prosthesis are available for almost 30 years and are used for
      the vocal rehabilitation of laryngectomees. Nevertheless there are no studies
      about this voice prosthesis. Especially because of the smaller external diameter
      of 5.5 mm differents to other voice prostheses may be expected.We analyzed the 10
      year patient documentation in retrospect.67 patients (63 m/4f) got the ESKA
      Herrmann voice prosthesis, which could be used with a mean lifetime of 131.4
      days. The main reason of changing the prostheses were dislocation (34/119), loss
      by coughing (34/119) and the leakage around the prostheses. In total a good voice
      was documented in 83.9% of the prostheses.ESKA-Herrmann voice prostheses are an
      alternative to other prostheses. Because of the smaller external diameter the
      dislocation and loss of the prosthesis occur more often than other models. But
      it's the only model that allows a designated spontaneous closure of the trachea
      esophageal fistula after prosthesis removal.

PMID- 22131185
TI  - Persistence in a single species CSTR model with suspended flocs and wall attached
      biofilms.
AB  - We consider a mathematical model for a bacterial population in a continuously
      stirred tank reactor (CSTR) with wall attachment. This is a modification of the
      Freter model, in which we model the sessile bacteria as a microbial biofilm. Our
      analysis indicates that the results of the algebraically simpler original Freter
      model largely carry over. In a computational simulation study, we find that the
      vast majority of bacteria in the reactor will eventually be sessile. However, we
      also find that suspended biomass is relatively more efficient in removing
      substrate from the reactor than biofilm bacteria.

PMID- 22131187
TI  - Effects of industrial tomato paste processing on ascorbic acid, flavonoids and
      carotenoids and their stability over one-year storage.
AB  - BACKGROUND: The effects of industrial tomato paste processing and long-term (12
      months) ambient storage on the content and stability of quercetin, kaempferol,
      ascorbic acid (AA), dehydroascorbic acid (DHAA), beta-carotene and lycopene were
      evaluated in a commercially produced tomato paste. RESULTS: The initial thermal
      treatment (hot break; 93  degrees C for 5 min) resulted in significant reductions
      in quercetin (54%), kaempferol (61%), AA (63%) and beta-carotene (30%), whereas
      subsequent processing steps (e.g. evaporation and sterilization) did not result
      in marked changes in these compounds. Lycopene was stable during hot break but
      decreased by 20% through evaporation and sterilization. The ratio of DHAA:vitamin
      C increased during hot break to 23%, whereas the ratio of DHAA:vitamin C remained
      relatively low in subsequent processing steps, indicating that AA was not
      oxidized. AA decreased with prolonged storage, with only 13% remaining at 12
      months. The carotenoids and quercetin remained stable through 12 months of
      ambient storage. CONCLUSIONS: Tomato pomace contained significant amounts of
      carotenoids and flavonoids, indicating that it may be an underutilized processing
      byproduct.

PMID- 22131188
TI  - Neuroprotective and neuroregenerative properties of metallothioneins.
AB  - Metallothioneins (MTs) are low-molecular weight cysteine- and metal-rich proteins
      with unquestionable metal binding capacity, antioxidant and anti-inflammatory
      properties, and a clear involvement in diverse physiological actions as
      inhibition of proapoptotic mechanisms, enhancement of cell survival, and tissue
      regeneration. Concurrent with this wide array of functions, MT-1/2 have been
      implicated in neuroprotection and neuroregeneration. The zinc binding capacity
      and antioxidant properties of MTs may account for most of their physiological
      features in the brain. However, some receptor-mediated actions of MT-1/2 have
      also been reported recently, a subject to be fully elucidated. This review
      analyses and updates the current knowledge on the actions of MTs related to
      neuroprotection and neuroregeneration in an effort to distinguish receptor
      mediated actions of MTs from those arising from its zinc binding capacity and its
      antioxidant properties.

PMID- 22131189
TI  - Pharmacological modulation of human mesenchymal stem cell chondrogenesis by a
      chemically oversulfated polysaccharide of marine origin: potential application to
      cartilage regenerative medicine.
AB  - Mesenchymal stem cells (MSCs) are considered as an attractive source of cells for
      cartilage engineering due to their availability and capacity for expansion and
      multipotency. Differentiation of MSC into chondrocytes is crucial to successful
      cartilage regeneration and can be induced by various biological agents, including
      polysaccharides that participate in many biological processes through
      interactions with growth factors. Here, we hypothesize that growth factor-induced
      differentiation of MSC can be increased by chemically oversulfated marine
      polysaccharides. To test our hypothesis, human adipose tissue-derived MSCs
      (hATSCs) were cultured in pellets with transforming growth factor (TGF)-beta1
      supplemented chondrogenic medium containing either the polysaccharide GY785 DR or
      its oversulfated isoform GY785 DRS. Chondrogenesis was monitored by the
      measurement of pellet volume, quantification of DNA, collagens,
      glycosaminoglycans (GAGs), and immunohistological staining. Our data revealed an
      increase in pellet volume, total collagens, and GAG production with GY785 DRS and
      chondrogenic medium. The enhanced chondrogenic differentiation of hATSC was
      further demonstrated by the increased expression of several chondrogenic markers
      by real-time reverse transcription-polymerase chain reaction. In addition,
      surface plasmon resonance analyses revealed that TGF-beta1 bound GY785 DRS with
      higher affinity compared to GY785 DR. In association with TGF-beta1, GY785 DRS
      was found to upregulate the phosphorylation of extracellular signal-regulated
      kinase 1/2, indicating that oversulfated polysaccharide affects the mitogen
      activated protein kinase signaling activity. These results demonstrate the
      upregulation of TGF-beta1-dependent stem cell chondrogenesis by a chemically
      oversulfated marine polysaccharide. This polysaccharide of marine origin is
      easily producible and therefore could be considered a promising additive to drive
      efficient and reliable MSC chondrogenesis for cartilage tissue engineering.

PMID- 22131191
TI  - Tracking and risk of abdominal obesity in the adolescence period in children aged
      7-15. The Cracow Longitudinal Growth Study.
AB  - OBJECTIVES: To examine the tracking of abdominal fat distribution from the age of
      7 to 15 years and to estimate the risk of abdominal obesity at 15 based on the
      occurrence of abdominal obesity at the ages 7-14 years in boys and girls.
      METHODS: The analysis was performed on 8-year longitudinal measurements of 315
      boys and 198 girls from Cracow, Poland. The stability of waist circumference (WC)
      and waist-to-height ratio (WHtR) got assessed by inter-age correlations. The
      degree of abdominal fatness continuation level was evaluated applying contingency
      tables with the chi2 test based on quartiles of WC and WHtR distribution. The
      risk of abdominal obesity at 15 was estimated using odds ratio (OR) and 95%
      confidence interval. RESULTS: Inter-age correlations between the 7(th) and 15(th)
      years were 0.73 and 0.67 in boys and 0.48 and 0.48 in girls for WC and WHtR,
      respectively. More than 51% girls and 62% boys with abdominal fat distribution at
      7 remained in the same category in adolescence period, while only 2% of them
      moved to the thin category at 15. The risk of abdominal obesity (WHtR) was
      highest in boys and girls with abdominal obesity at 7 (OR = 5.46 and OR = 6.19,
      respectively) and, additionally, in girls at 12 (OR = 5.59). CONCLUSION: The risk
      of abdominal obesity was indicated already at 7 in boys and girls. Continuation
      of the abdominal fat distribution confirmed in about 60% acknowledges that the
      type of fat distribution seems to be determined as early as in the 7-year-olds.

PMID- 22131192
TI  - Neuroradiological and neurofunctional examinations for patients with 22q11.2
      deletion.
AB  - Since the neuroradiological features of patients with 22q11.2 deletion syndrome
      are not well-understood, examinations using functional imaging were performed in
      this study. Brain magnetic resonance imaging (MRI) and 1H-magnetic resonance
      spectroscopy (MRS) were performed using a clinical 3-Tesla MR imager in 4
      patients with 22q11.2 deletion syndrome (2 boys and 2 girls; aged 2-6 years.) and
      20 age- and sex-matched healthy control subjects. Furthermore, interictal 123I
      iomazenil (IMZ) single photon emission computed tomography (SPECT) was examined
      in 2 of the 4 patients. Among the 4 patients with 22q11.2 deletion syndrome, 2
      patients showed polymicrogyria and 1 patient showed agyria. Those patients with
      brain malformations also showed abnormal brain artery patterns and decreased
      accumulation of IMZ in 123I-IMZ SPECT. Although all 4 patients showed epileptic
      discharges in their electroencephalograms (EEG), one patient with polymicrogyria
      had no seizure episodes. Decreases in gamma-aminobutyric acid (GABA)
      corresponding to the areas of polymicrogyria and/or epileptic discharges in EEG
      were shown in all patients except for the patient with agyria. Although
      consistent evidence was not seen in patients with 22q11.2 deletion syndrome in
      this study, brain malformations and disturbances of the GABAergic nervous system
      would be underlying mechanisms of the neurodevelopmental abnormalities in this
      syndrome.

PMID- 22131194
TI  - Electrochemistry of titanium dioxide: some aspects and highlights.
AB  - Selected problems of electrochemical synthesis, characterization and applications
      of titanium dioxide are reviewed. These issues have attracted considerable
      attention from addressing purely academic questions up to promising applications
      in devices for energy storage and energy conversion.

PMID- 22131195
TI  - Anti-inflammatory activities of aqueous extract of Mesona procumbens in
      experimental mice.
AB  - BACKGROUND: Mesona procumbens is consumed as a herbal drink and jelly-type
      dessert in Taiwan. The aim of this study was to determine the mechanism of anti
      inflammatory activities of the aqueous extract of M. procumbens (AMP) using the
      lambda-carrageenin (Carr)-induced mouse paw oedema model. The fingerprint
      chromatogram of AMP was obtained by high-performance liquid chromatography (HPLC)
      analysis. To investigate the anti-inflammatory mechanism of AMP, the activities
      of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)
      and the level of malondialdehyde (MDA) in paw oedema were monitored. Serum nitric
      oxide (NO), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) were also evaluated. RESULTS: The fingerprint chromatogram from HPLC
      indicated that AMP contained protocatechuic acid, chlorogenic acid, vanillic acid
      and caffeic acid. In the anti-inflammatory test, AMP decreased paw oedema after
      Carr administration and increased the CAT, SOD and GPx activities and decreased
      the MDA level in paw oedema at 5 h after Carr injection. AMP also affected the
      serum NO, TNF-alpha and IL-1beta levels at 5 h after Carr injection. Western
      blotting revealed that AMP decreased the expression of Carr-induced inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). CONCLUSION: Mesona
      procumbens has the potential to provide a therapeutic approach to inflammation
      associated disorders.

PMID- 22131196
TI  - Allyl isothiocyanate as a potential inducer of paraoxonase-1--studies in cultured
      hepatocytes and in mice.
AB  - In this study, we tested the ability of structure-related isothiocyanates to
      induce the antiatherogenic enzyme paraoxonase-1 (PON1) in cultured hepatocytes.
      Allyl isothiocyanate (AITC), phenylethyl isothiocyanate (PEITC), and sulforaphane
      (SFN), but not butyl isothiocyanate (BITC) resulted in dose-dependent induction
      of PON1 transactivation in Huh7 cells in vitro. Induction of PON1 due to AITC was
      inhibited by the selective peroxisome proliferator-activated receptor gamma
      antagonist T0070907. AITC was used in a subsequent in vivo study in mice (n = 10
      per group, Western-type diet) to test its PON1 inducing activity. Unlike in
      cultured hepatocytes, AITC supplementation (15 mg/kg body weight) did not
      increase hepatic PON1 mRNA and protein levels in mice. Thus, it is suggested that
      AITC may be a potent inducer of PON1 in vitro, but not in mouse liver in vivo.

PMID- 22131197
TI  - Attachment and hikikomori: a psychosocial developmental model.
AB  - BACKGROUND: Hikikomori (acute social withdrawal) is a social issue in Japan that
      affects both the society and the lives of the individual sufferers. AIMS: This
      study aims to connect attachment theory and hikikomori by using a culturally
      sensitive psychosocial developmental model that outlines the various stages of
      attachment throughout the developmental years. METHOD: Twenty-four hikikomori
      sufferers and 60 comparison group participants were given questionnaires
      assessing parent and peer relationships, temperament and school experiences.
      RESULTS: We found the hikikomori participants had a higher incidence of
      ambivalent attachment, reported more parental and peer rejection and bullying,
      and expressed greater temperamental shyness. Path analysis supported our
      developmental model. We found that shy temperament and parental rejection
      predicted ambivalent attachment, which when coupled with peer rejection predicted
      hikikomori. Our model implies that treatment and prevention may require attention
      to attachment insecurities in early childhood, peer rejection in middle childhood
      and/or early adolescence. CONCLUSION: We believe it is helpful in understanding
      hikikomori to first understand how the attachment system balances security with
      exploration and the anxiety associated with novelty and challenge. Finally, we
      examine implications of the model for intervention, treatment and future
      research.

PMID- 22131198
TI  - Stigmatization of people with mental illness among inhabitants of a rural
      community in northern Nigeria.
AB  - BACKGROUND: Despite the fact that mental illness is a common problem in society,
      people's perception of the mentally ill and community attitude towards them is
      still rather poor, making their rehabilitation and reintegration into society an
      uphill task. AIMS: To examine the stigmatization of people with mental illness
      within a rural community and identify the socio-demographic variables involved.
      METHOD: A cross-sectional descriptive study using a multi-stage random sampling
      technique to obtain data through an interviewer-administered questionnaire to 325
      adult inhabitants of a rural community in Nigeria. RESULTS: The results showed
      widespread ignorance about causation, mode of transmission and remedies available
      for mental illness, with only 0.9% of respondents attributing mental illness to
      brain disease. The others attributed it to spiritual attack, punishment for evil
      doing and illicit psychoactive substance use, among other things. Negative views
      about the mentally ill were also widely expressed resulting in discriminatory
      practices. CONCLUSION: Stigmatization of people with mental illness is still
      rampant in our community. There is a need for adequate public education about the
      causes and mode of transmission of mental illness and the treatment options
      available in the community.

PMID- 22131199
TI  - Endoglin in liver fibrosis.
AB  - Liver fibrosis occurs in most types of chronic liver diseases and is
      characterized by excessive accumulation of extracellular matrix proteins, leading
      to disruption of tissue function and eventually organ failure. Transforming
      growth factor (TGF)-beta represents an important pro-fibrogenic factor and
      aberrant TGF-beta action has been implicated in many disease processes of the
      liver. Endoglin is a TGF-beta co-receptor expressed mainly in endothelial cells
      that has been shown to differentially regulates TGF-beta signal transduction by
      inhibiting ALK5-Smad2/3 signalling and augmenting ALK1-Smad1/5 signalling. Recent
      reports demonstrating upregulation of endoglin expression in pro-fibrogenic cell
      types such as scleroderma fibroblasts and hepatic stellate cells have led to
      studies exploring the potential involvement of this TGF-beta co-receptor in organ
      fibrosis. A recent article by Meurer and colleagues now shows that endoglin
      expression is increased in transdifferentiating hepatic stellate cells in vitro
      and in two different models (carbon tetrachloride intoxication and bile duct
      ligation) of liver fibrosis in vivo. Moreover, they show that endoglin
      overexpression in hepatic stellate cells is associated with enhanced TGF-beta
      driven Smad1/5 phosphorylation and alpha-smooth muscle actin production without
      altering Smad2/3 signaling. These findings suggest that endoglin may play an
      important role in hepatic fibrosis by altering the balance of TGF-beta signaling
      via the ALK1-Smad1/5 and ALK-Smad2/3 pathways and raise the possibility that
      targeting endoglin expression in transdifferentiating hepatic stellate cells may
      represent a novel therapeutic strategy for the treatment of liver fibrosis.

PMID- 22131200
TI  - MEK/ERK inhibitors: proof-of-concept studies in lung fibrosis.
AB  - There is no therapy for chronic fibroproliferative diseases, in spite of the fact
      that current health statistics suggest that these (which include cardiovascular
      disease, pulmonary fibrosis, diabetic nephropathy, liver cirrhosis and systemic
      sclerosis) have been estimated to cause approximately 45% of the deaths in the
      developed world. Recently, many studies have shown that mitogen activated protein
      kinases (MAPKs) are activated in response to fibrogenic agents and contribute to
      the formation and function of the myofibroblast, the critical cell type
      responsible for excessive scarring. A recent report by Madala and colleagues (Am
      J Respir Cell Mol Biol, 2011) has provided a proof-of-concept study showing that
      the specific MEK inhibitor ARRY-142886 (ARRY) can both suppress the progression
      of fibrosis and reverse an animal model of lung fibrosis. Thus MEK inhibition
      could be a valuable method to treat lung fibrosis.

PMID- 22131201
TI  - Limbal epithelial stem cells: role of the niche microenvironment.
AB  - The cornea contains a reservoir of self-regenerating epithelial cells that are
      essential for maintaining its transparency and good vision. The study of stem
      cells in this functionally important organ has grown over the past four decades,
      partly due to the ease with which this tissue is visualized, its accessibility
      with minimally invasive instruments, and the fact that its stem cells are
      segregated within a transitional zone between two functionally diverse epithelia.
      While human, animal, and ex vivo models have been instrumental in progressing the
      corneal stem cell field, there is still much to be discovered about this
      exquisitely sensitive window for sight. This review will provide an overview of
      the human cornea, where its stem cells reside and how components of the
      microenvironment including extracellular matrix proteins and their integrin
      receptors are thought to govern corneal stem cell homeostasis.

PMID- 22131203
TI  - Ergolytic/ergogenic effects of creatine on aerobic power.
AB  - This study evaluated the effects of creatine (Cr) loading and sex differences on
      aerobic running performance. 27 men (mean+/-SD; age: 22.2+/-3.1 years, ht:
      179.5+/-8.7 cm, wt: 78.0+/-9.8 kg) and 28 women (age: 21.2+/-2.1 years, ht:
      166.0+/-5.8 cm, wt: 63.4+/-8.9 kg) were randomly assigned to either creatine (Cr,
      di-creatine citrate; n=27) or a placebo (PL; n=28) group, ingesting 1 packet 4
      times daily (total of 20 g/day) for 5 days. Aerobic power (maximal oxygen
      consumption: VO2max) was assessed before and after supplementation using open
      circuit spirometry (Parvo-Medics) during graded exercise tests on a treadmill. 4
      high-speed runs to exhaustion were conducted at 110, 105, 100, and 90% of peak
      velocity to determine critical velocity (CV). Distances achieved were plotted
      over times-to-exhaustion and linear regression was used to determine the slopes
      (critical velocity, CV) assessing aerobic performance. The results indicated that
      Cr loading did not positively or negatively influence VO2max, CV, time to
      exhaustion or body mass (p>0.05). These results suggest Cr supplementation may be
      used in aerobic running activities without detriments to performance.

PMID- 22131202
TI  - Evaluation of qualitative methods for phenotyping brachymesophalangia-V from
      radiographs of children.
AB  - OBJECTIVE: Brachymesophalangia-V (BMP-V), the general term for a short and broad
      middle phalanx of the 5th digit, presents both alone and in a large number of
      complex brachydactylies and developmental disorders. Past anthropological and
      epidemiological studies of growth and development have examined the prevalence of
      BMP-V because small developmental disorders may signal more complex disruptions
      of skeletal growth and development. Historically, however, consensus on
      qualitative phenotype methodology has not been established. In large-scale, non
      clinical studies such as the Fels Longitudinal Study and the Jiri Growth Study,
      quantitative assessment of the hand is not always the most efficient manner of
      screening for skeletal dysmorphologies. The current study evaluates qualitative
      phenotyping techniques for BMP-V used in past anthropological studies of growth
      and development to establish a useful and reliable screening method for large
      study samples. METHODS: A total of 1,360 radiographs from Jiri Growth Study
      participants aged 3-18 years were evaluated. BMP-V was assessed using three
      methods: (1) subjective evaluation of length and width of the bone; (2)
      comparison with skeletal age-matched radiographs; and (3) subjective evaluation
      of the length of the middle 4th and 5th phalanges. RESULTS: We found that the
      method that uses skeletal age-matched reference radiographs is the better tool
      for assessing BMP-V because it considers the shape, rather than solely the length
      and width of the bone, which can be difficult to judge accurately without
      measurement. This study highlights the complexity of phenotypic assessment of BMP
      V and by extension other brachydactylies.

PMID- 22131204
TI  - Diet and exercise improve neutrophil to lymphocyte ratio in overweight
      adolescents.
AB  - Neutrophil to lymphocyte ratio and levels of pro-inflammatory cytokines were
      evaluated in overweight, male Chinese adolescents upon completing a 4-week diet
      and physical exercise intervention. 43 recruited, non-randomized adolescents
      (body mass index >25 kg/m2) completed the controlled study. Anthropometric and
      biologic parameters were measured pre- and post-intervention. After the 4-week
      intervention, participants exhibited a significant decrease in body mass, body
      mass index, percentage body fat, basal heart rate, diastolic blood pressure, and
      all body shape indices tested. A significant decrease in serum lipids (except
      high-density lipoprotein cholesterol) and insulin levels was observed post
      intervention. The neutrophil to lymphocyte ratio was significantly lower post
      intervention. Bivariate correlation analyses showed that decrement in
      Deltaneutrophil to lymphocyte ratio significantly correlated with decrement in
      Deltainterleukin-6 and Deltawhite blood cell count. Thus, a 4-week diet and
      physical exercise intervention significantly reduces the neutrophil to lymphocyte
      ratio in a population of overweight, male adolescents. Weight loss caused by the
      intervention was associated with a significant decrease of pro-inflammatory
      cytokine levels.

PMID- 22131205
TI  - Secularism needs a distinctive medical voice.

PMID- 22131206
TI  - Poor care for elderly people has been made worse by lack of training.

PMID- 22131207
TI  - Let someone else sign off sick notes.

PMID- 22131208
TI  - The gender agenda.

PMID- 22131209
TI  - Middle income countries need to "share the burden" of the fight against HIV and
      AIDS.

PMID- 22131210
TI  - Why shouldn't private companies run failing hospitals?

PMID- 22131211
TI  - Warts and all at last: HPV vaccination.

PMID- 22131212
TI  - Higher death rate among hospital patients admitted at weekends has several
      causes, report finds.

PMID- 22131213
TI  - UK government signals its support for telemedicine.

PMID- 22131214
TI  - Barnardo's misleading survey: publicity at what cost?

PMID- 22131215
TI  - Whistleblowers say there was a "bullying culture" at England's care services
      watchdog.

PMID- 22131218
TI  - Draft genome sequence of Penicillium marneffei strain PM1.
AB  - Penicillium marneffei is the most important thermal dimorphic, pathogenic fungus
      endemic in China and Southeast Asia and is particularly important in HIV-positive
      patients. We report the 28,887,485-bp draft genome sequence of P. marneffei,
      which contains its complete mitochondrial genome, sexual cycle genes, a high
      diversity of Mp1p homologues, and polyketide synthase genes.

PMID- 22131219
TI  - The rise of self-assembled monolayers for fabricating electrochemical biosensors-
      an interfacial perspective.
AB  - Electrochemical biosensors have witnessed a tremendous growth in nanotechnology
      and in depth characterisation over the last two decades. In particular,
      modification of surfaces with self-assembled monolayers (SAMs) has provided a
      molecular control of the interfaces, which has paved the way to fabricate
      improved biosensing devices. Here we focus on the important advances of using
      SAMs in enzyme electrodes and affinity biosensors such as for peptides, DNA and
      antibodies.

PMID- 22131220
TI  - Characterisation of grain quality in diverse sorghum germplasm using a Rapid
      Visco-Analyzer and near infrared reflectance spectroscopy.
AB  - BACKGROUND: Twenty-two diverse sorghum landraces, classified as normal and opaque
      types obtained from Ethiopia, were characterised for grain quality parameters
      using near infra-red spectroscopy (NIRS), chemical and Rapid Visco-Analyzer (RVA)
      characteristics. RESULTS: Protein content ranged from 77 to 182 g kg(-1), and
      starch content from 514 to 745 g kg(-1). The NIRS analysis indicated the pig
      faecal digestible energy range from 14.6 to 15.7 MJ kg(-1) as fed, and the ileal
      digestible energy range from 11.3 to 13.9 MJ kg(-1) as fed. The normal sorghums
      had higher digestible energy than the opaque sorghums, which exhibited lower RVA
      viscosities, and higher pasting temperatures and setback ratios. The RVA
      parameters were positively correlated with the starch content and negatively
      correlated with the protein content. The normal and opaque types formed two
      distinct groups based on principal component and cluster analyses. CONCLUSION:
      The landraces were different for the various grain quality parameters with some
      landraces displaying unique RVA and NIRS profiles. This study will guide
      utilisation of the sorghum landraces in plant improvement programs, and provides
      a basis for further studies into how starch and other constituents behave in and
      affect the properties of these landraces.

PMID- 22131221
TI  - Protein monoubiquitination and polyubiquitination generate structural diversity
      to control distinct biological processes.
AB  - Ubiquitination involves the attachment of ubiquitin (Ub) to lysine residues on
      substrate proteins or itself, which can result in protein monoubiquitination or
      polyubiquitination. Polyubiquitination through different lysines (seven) or the N
      terminus of Ub can generate different protein-Ub structures. These include
      monoubiquitinated proteins, polyubiqutinated proteins with homotypic chains
      through a particular lysine on Ub or mixed polyubiquitin chains generated by
      polymerization through different Ub lysines. The ability of the ubiquitination
      pathway to generate different protein-Ub structures provides versatility of this
      pathway to target proteins to different fates. Protein ubiquitination is
      catalyzed by Ub-conjugating and Ub-ligase enzymes, with different combinations of
      these enzymes specifying the type of Ub modification on protein substrates. How
      Ub-conjugating and Ub-ligase enzymes generate this structural diversity is not
      clearly understood. In the current review, we discuss mechanisms utilized by the
      Ub-conjugating and Ub-ligase enzymes to generate structural diversity during
      protein ubiquitination, with a focus on recent mechanistic insights into protein
      monoubiquitination and polyubiquitination.

PMID- 22131222
TI  - ECS-3: a crystalline hybrid organic-inorganic aluminosilicate with open porosity.

PMID- 22131223
TI  - T-one insensitive steady state imaging: a framework for purely T2-weighted
      TrueFISP.
AB  - A new conceptual framework called T-one insensitive steady state imaging is
      proposed for fast generation of MR images with pure T(2) contrast. This is
      accomplished by imaging between nonequally spaced inversion pulses, with the
      magnetization vector alternatively residing in states parallel and antiparallel
      to B(0) for durations TP(i) and TA(i), respectively. With TP(i) and TA(i)
      adequately chosen, identical signal time evolution can be obtained for different
      T(1) values, i.e., T(1) contrast can efficiently be removed from resultant
      images. As a specific realization of this principle, T-one insensitive steady
      state imaging sequences are presented which use True free induction steady
      precession readout blocks between the inversion pulses. While the conventional
      True free induction steady precession signal time course would be determined by
      both T(2) and T(1), a pure T(2) dependence is realized with successfully
      suppressed influence of longitudinal relaxation, and images with essentially T(2)
      contrast alone are obtained. Analytical expressions are provided for the
      description of the ideal signal behavior, which help in creating pathways for
      sequence parameter optimization. The performance of the technique is analyzed
      with Bloch equation simulations. In vivo results obtained in healthy volunteers
      and brain tumor patients are presented.

PMID- 22131224
TI  - Aerobic exercise intensity influences hypotension following concurrent exercise
      sessions.
AB  - The study investigated whether resistance and aerobic concurrent exercise (CE)
      with different intensities influenced postexercise hypotension (PEH). 21 healthy
      men (20.7+/-0.7 yr) performed 4 sessions: control [CTL 60 min of rest], and CE1,
      CE2, and CE3 consisting respectively of 2 sets of 6 exercises at 80% 1RM followed
      by 30 min of cycle ergometer exercise at 50%, 65%, and 80% of peak oxygen
      consumption (VO2peak). All sessions lasted approximately 60 min and began with
      resistance prior to aerobic sessions. Systolic (SBP) and diastolic (DBP) blood
      pressure (BP) were assessed at baseline and every 10 min during 120-min recovery.
      The magnitude of SBP decrease was similar after all CE sessions [CE1: 4.2+/-2.5
      mmHg; CE2: 4.8+/-2.7 mmHg; CE3: 6.0+/-2.0 mmHg; p=0.06], but the PEH lasted
      approximately 1 h longer following CE2 and CE3 [120 min] compared to CE1 [60-70
      min] (P<0.05). The magnitude of DBP decrease was slightly greater after CE3 and
      CE2 [2 mmHg] than after CE1 [1 mmHg] (P<0.05), being longer following CE3 [60
      min] compared to CE2 and CE1 [40 min] (P<0.05). In conclusion, CE sessions
      combining resistance and aerobic sessions elicited PEH, especially when the
      intensity of the aerobic exercise was higher than 65% VO2peak.

PMID- 22131225
TI  - Compelling advantages of negative ion mode detection in high-mass MALDI-MS for
      homomeric protein complexes.
AB  - Chemical cross-linking in combination with high-mass MALDI mass spectrometry
      allows for the rapid identification of interactions and determination of the
      complex stoichiometry of noncovalent protein-protein interactions. As the
      molecular weight of these complexes increases, the fraction of multiply charged
      species typically increases. In the case of homomeric complexes, signals from
      multiply charged multimers overlap with singly charged subunits. Remarkably,
      spectra recorded in negative ion mode show lower abundances of multiply charged
      species, lower background, higher reproducibility, and, thus, overall cleaner
      spectra compared with positive ion mode spectra. In this work, a dedicated high
      mass detector was applied for measuring high-mass proteins (up to 200 kDa) by
      negative ion mode MALDI-MS. The influences of sample preparation and instrumental
      parameters were carefully investigated. Relative signal integrals of multiply
      charged anions were relatively independent of any of the examined parameters and
      could thus be approximated easily for the spectra of cross-linked complexes. For
      example, the fraction of doubly charged anions signals overlapping with the
      signals of singly charged subunits could be more precisely estimated than in
      positive ion mode. Sinapinic acid was found to be an excellent matrix for the
      analysis of proteins and cross-linked protein complexes in both ion modes. Our
      results suggest that negative ion mode data of chemically cross-linked protein
      complexes are complementary to positive ion mode data and can in some cases
      represent the solution phase situation better than positive ion mode.

PMID- 22131226
TI  - Statistical analysis of ion mobility spectrometry. I. Unbiased and guided replica
      exchange molecular dynamics.
AB  - Achieving (bio)macromolecular structural assignment from the interpretation of
      ion mobility spectrometry (IMS) experiments requires successful comparison with
      computer modeling. Replica-exchange molecular dynamics simulations with suitable
      force fields not only offer a convenient framework to locate relevant
      conformations, especially in the case of multiple-funnel energy landscapes, but
      they are also well suited to statistical analyses. In the present paper, we
      discuss two extensions of the method used to improve its efficiency in the
      context of IMS. Two doubly-protonated polyalanines [RA(4)XA(4)K + 2H](2+) with
      X=V and D appear as favorable cases for which the calculated collision cross
      section distributions naturally agree with the measurements, providing reliable
      candidate structures. For these compounds, a careful consideration of other order
      parameters based on the weighted histogram method resolves several otherwise
      hidden underlying conformational families. In the case of a much larger peptide
      exhibiting bistability, assignment is more difficult but could be achieved by
      guiding the sampling with an umbrella potential using the square gyration radius
      as the biasing coordinate. Applied to triply protonated bradykinine, the two
      presented methods indicate that different conformations compatible with the
      measurements are very close in energy.

PMID- 22131227
TI  - Quaternary diamines as mass spectrometry cleavable crosslinkers for protein
      interactions.
AB  - Mapping protein interactions and their dynamics is crucial to defining
      physiologic states, building effective models for understanding cell function,
      and to allow more effective targeting of new drugs. Crosslinking studies can
      estimate the proximity of proteins, determine sites of protein-protein
      interactions, and have the potential to provide a snapshot of dynamic
      interactions by covalently locking them in place for analysis. Several major
      challenges are associated with the use of crosslinkers in mass spectrometry,
      particularly in complex mixtures. We describe the synthesis and characterization
      of a MS-cleavable crosslinker containing cyclic amines, which address some of
      these challenges. The DC4 crosslinker contains two intrinsic positive charges,
      which allow crosslinked peptides to fragment into their component peptides by
      collision-induced dissociation (CID) or in-source decay. Initial fragmentation
      events result in cleavage on either side of the positive charges so crosslinked
      peptides are identified as pairs of ions separated by defined masses. The
      structures of the component peptides can then be robustly determined by MS(3)
      because their fragmentation products rearrange to generate a mobile proton. The
      DC4 crosslinking reagent is stable to storage, highly reactive, highly soluble (1
      M solutions), quite labile to CID, and MS(3) results in productive backbone
      fragmentation.

PMID- 22131229
TI  - Simulation of ion motion at atmospheric pressure: particle tracing versus
      electrokinetic flow.
AB  - Results obtained with two computational approaches for the simulation of ion
      motion at elevated pressure are compared with experimentally derived ion current
      data. The computational approaches used are charged particle tracings with the
      software package SIMION ver. 8 and finite element based calculations using the
      software package Comsol Multiphysics ver. 4.0/4.0a. The experimental setup
      consisted of a tubular corona discharge ion source coupled to a cylindrical
      measurement chamber held at atmospheric pressure. Generated ions are flown into
      the chamber at essentially subsonic laminar isothermal conditions. In the
      simulations, strictly stationary conditions were assumed. The results show very
      good agreement between the SIMION/SDS model and experimental data. For the Comsol
      model, only qualitative agreement is observed.

PMID- 22131228
TI  - Noncovalent complexation of monoamine neurotransmitters and related ammonium ions
      by tetramethoxy tetraglucosylcalix[4]arene.
AB  - The noncovalent complexation of monoamine neurotransmitters and related ammonium
      and quaternary ammonium ions by a conformationally flexible tetramethoxy
      glucosylcalix[4]arene was studied by electrospray ionization Fourier transform
      ion cyclotron resonance (ESI-FTICR) mass spectrometry. The glucosylcalixarene
      exhibited highest binding affinity towards serotonin, norepinephrine,
      epinephrine, and dopamine. Structural properties of the guests, such as the
      number, location, and type of hydrogen bonding groups, length of the alkyl spacer
      between the ammonium head-group and the aromatic ring structure, and the degree
      of nitrogen substitution affected the complexation. Competition experiments and
      guest-exchange reactions indicated that the hydroxyl groups of guests participate
      in intermolecular hydrogen bonding with the glucocalixarene.

PMID- 22131230
TI  - Automated hydrogen/deuterium exchange electron transfer dissociation high
      resolution mass spectrometry measured at single-amide resolution.
AB  - Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a well established
      method for the measurement of solution-phase deuterium incorporation into
      proteins, which can provide insight into protein conformational mobility.
      However, most HDX measurements are constrained to regions of the protein where
      pepsin proteolysis allows detection at peptide resolution. Recently, single-amide
      resolution deuterium incorporation has been achieved by limiting gas-phase
      scrambling in the mass spectrometer. This was accomplished by employing a
      combination of soft ionization and desolvation conditions coupled with the
      radical-driven fragmentation technique electron transfer dissociation (ETD).
      Here, a hybrid LTQ-Orbitrap XL is systematically evaluated for its utility in
      providing single-amide deuterium incorporation for differential HDX analysis of a
      nuclear receptor upon binding small molecule ligands. We are able to show that
      instrumental parameters can be optimized to minimize scrambling and can be
      incorporated into an established and fully automated HDX platform making
      differential single-amide HDX possible for bottom-up analysis of complex systems.
      We have applied this system to determine differential single amide resolution HDX
      data for the peroxizome proliferator activated receptor bound with two ligands of
      interest.

PMID- 22131232
TI  - Asymmetric dimethylarginine may mediate increased heat pain threshold in
      experimental chronic kidney disease.
AB  - BACKGROUND: Thermal sensitivity in uraemia is decreased. Non-selective synthetic
      nitric oxide synthase (NOS) inhibitors significantly attenuate thermal
      hyperalgesia in preclinical models. The aim of our study was to evaluate the
      effect of experimental uraemia, which is associated with an increase of the
      endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), on thermal
      sensitivity in rats. Furthermore, we intended to study the effect of chronic ADMA
      infusion alone on thermal sensitivity. METHODS: Male Sprague-Dawley rats (n =
      54), 10 weeks old, weight 370-430 g, were randomly assigned to three groups
      receiving either (i) isotonic saline or (ii) ADMA via osmotic mini pumps or (iii)
      underwent 5/6 nephrectomy (Nx). After 14 days, 50% of all animals from all groups
      underwent thermal sensitivity testing and terminal blood draw. After 28 days, the
      remaining animals underwent the same procedures. Thermal sensitivity examination
      was performed by the hot-plate test, measuring time from heat exposition to first
      paw licking or jumping of the animal. RESULTS: While the median [interquartile
      range] latency time between heat exposition to first paw licking or jumping of
      the animal in the NaCl infusion group remained unchanged between Day 14 (8.4
      [6.75-11.50] s) and Day 28 (7.35 [6.10-7.90] s) both, ADMA infusion and 5/6
      nephrectomy tended to increase the thermal pain threshold at Day 14 (9.25 [6.55
      12.18] s) and (9.50 [5.8 +/- 11.0] s), respectively, compared to NaCl on Day 14
      (8.4 [6.75-11.50] s). This difference became statistical significant at Day 28
      where the median latency time in the ADMA group (13.10 [11.85-15.95] s) and in
      the 5/6 Nx group (13.50 [10.85-17.55] s) were significantly higher than in the
      NaCl group (7.35 [6.10-7.90] s). CONCLUSIONS: Induction of progressive renal
      failure in rats by 5/6 nephrectomy, which is accompanied by a marked increase of
      the serum levels of the endogenous NOS inhibitor ADMA, leads to a significantly
      increased heat pain threshold at 28 days. The sole infusion of ADMA into healthy
      rats leads to the same increase in heat pain threshold.

PMID- 22131231
TI  - Ikappab-zeta plays an important role in the ERK-dependent dysregulation of
      malaria parasite GPI-induced IL-12 expression.
AB  - Plasmodium falciparum glycosylphosphatidylinositols (GPIs) have been proposed as
      malaria pathogenic factors based on their ability to induce proinflammatory
      responses in macrophages and malaria-like symptoms in mice. Parasite GPIs induce
      the production of inflammatory cytokines by activating the mitogen-activated
      protein kinase (MAPK) and NF-kappaB signaling pathways. Importantly, inhibition
      of the extracellular-signal-regulated kinase (ERK) pathway upregulates a subset
      of cytokines, including IL-12. We investigated the role of nuclear transcription
      factor, IkappaB-zeta, in the GPI-induced dysregulated expression of IL-12 on
      inhibition of the ERK pathway. GPIs efficiently induced the expression of IkappaB
      zeta in macrophages regardless of whether cells were pretreated or untreated with
      ERK inhibitors, indicating that ERK has no role in IkappaB-zeta expression.
      However, on ERK inhibition followed by stimulation with GPIs, NF-kappaB binding
      to Il12b promoter kappaB site was markedly increased, suggesting that the ERK
      pathway regulates Il12b transcription. Knockdown of IkappaB-zeta using siRNA
      markedly reduced the GPI-induced IL-12 production and abrogated the dysregulated
      IL-12 production in ERK inhibited cells. Together these results demonstrate that
      ERK modulates IL-12 expression by regulating IkappaB-zeta-dependent binding of NF
      kappaB transcription factors to Il12b gene promoter. Additionally, our finding
      that IkappaB-zeta can be knocked down efficiently in primary macrophages is
      valuable for studies aimed at gaining further insights into IkappaB-zeta
      function.

PMID- 22131233
TI  - Disintegration of colonic epithelial tight junction in uremia: a likely cause of
      CKD-associated inflammation.
AB  - BACKGROUND: Inflammation is a constant feature and a major mediator of the
      progression of chronic kidney disease (CKD) and its numerous complications. There
      is increasing evidence pointing to the impairment of intestinal barrier function
      and its contribution to the prevailing inflammation in advanced CKD. Under normal
      condition, the intestinal epithelium and its apical tight junction prevent entry
      of the luminal microorganisms, harmful microbial by-products and other noxious
      contents in the host's internal milieu. This study was designed to test the
      hypothesis that impaired intestinal barrier function in uremia must be due to
      disruption of the intestinal tight junction complex. METHODS: Sprague-Dawley (SD)
      rats were randomized to undergo 5/6 nephrectomy (CKD) or sham-operation (control)
      and observed for 8 weeks. In a separate experiment, SD rats were rendered uremic
      by addition of 0.7% adenine to their food for 2 weeks and observed for an
      additional 2 weeks. Rats consuming a regular diet served as controls. The animals
      were then euthanized and their colons were removed and processed for expression
      of the key constituents of the tight junction complex using real-time polymerase
      chain reaction, western blot analysis and immunohistological examinations.
      RESULTS: The CKD groups showed elevated plasma urea and creatinine, reduced
      creatinine clearance, thickened colonic wall and heavy infiltration of
      mononuclear leukocytes in the lamina propria. This was associated with marked
      reductions in protein expressions of claudin-1 (70-90%), occludin (50-70%) and ZO
      1 (80-90%) in the colonic mucosa in both CKD models compared with the
      corresponding controls. The reduction in the abundance of the given proteins was
      confirmed by immunohistological examinations. In contrast, messenger RNA
      abundance of occludin, claudin-1 and ZO-1 was either unchanged or elevated
      pointing to the post-transcriptional/post-translational modification as a cause
      of the observed depletion of the tight junction proteins. CONCLUSION: The study
      revealed, for the first time, that uremia results in depletion of the key protein
      constituents of the colonic tight junction, a phenomenon which can account for
      the impaired intestinal barrier function and contribute to the systemic
      inflammation in CKD.

PMID- 22131234
TI  - Non-IgA mesangioproliferative glomerulonephritis: a benign entity?
AB  - BACKGROUND: Non-IgA mesangioproliferative glomerulonephritis is a well recognized
      but less studied entity. The clinical manifestations, treatment response and long
      term outcome have not been clearly defined. METHODS: This single-centre study
      included patients with biopsy-proven non-IgA mesangioproliferative
      glomerulonephritis who had been on regular follow-up for >3 years. Their clinical
      features at presentation, response to therapy and long-term renal outcome are
      addressed in this study. RESULTS: Nephrotic syndrome developed in 51 of 57
      patients (89.4%). The majority of them--34 of 51(80%)--were steroid sensitive and
      had either infrequent or no relapse. However, steroid-dependent nephrotic
      syndrome occurred in eight patients (15.6%), while steroid resistance occurred in
      nine patients (17.6 %). Thirteen patients developed chronic kidney disease (CKD)
      with three progressing to end-stage renal disease, three to CKD Stage 4 and seven
      to CKD Stage 3. CONCLUSIONS: Non-IgA mesangioproliferative glomerulonephritis is
      a disease, which is not benign, and is associated with significant treatment
      related morbidity.

PMID- 22131235
TI  - Search for genetic association between IgA nephropathy and candidate genes
      selected by function or by gene mapping at loci IGAN2 and IGAN3.
AB  - BACKGROUND: IgA nephropathy (IgAN) is not generally considered a hereditary
      disease, even though extensive evidence suggests an undefined genetic influence.
      Linkage analysis identified a number of genome regions that could contain
      variations linked to IgAN. METHODS: In this case-control association study, genes
      possibly involved in the development of IgAN were investigated. DNA samples from
      460 North Italian patients with IgAN and 444 controls were collected. Candidate
      genes were selected based on their possible functional involvement (6 genes) or
      because of their location within linkage-identified genomic regions IGAN2 and
      IGAN3 (5 and 13 genes within chromosome 4q26-31 and 17q12-22, respectively). One
      hundred and ninety-two tag and functional single-nucleotide polymorphisms (SNPs)
      were typed with Veracode GoldenGate technology (Illumina). RESULTS: C1GALT1
      showed an association with IgAN (rs1008898: P = 0.0019 and rs7790522: P =
      0.0049). Associations were found when the population was stratified by gender
      (C1GALT1, CD300LG, GRN, ITGA2B, ITGB3 in males and C1GALT1, TRPC3, B4GALNT2 in
      females) and by age (TLR4, ITGB3 in patients aged <27 years). Furthermore,
      rs7873784 in TLR4 showed an association with proteinuria (G allele: P = 0.0091;
      GG genotype: P = 0.0077). CONCLUSIONS: Age and gender are likely to evidence
      distinct immunological and inflammatory reactions leading to individual
      susceptibility to IgAN. Overall, a genetic predisposition to sporadic IgAN was
      found. We might hypothesize that C1GALT1 and TLR4 polymorphisms influence the
      risk to develop IgAN and proteinuria, respectively.

PMID- 22131236
TI  - Single shot concentric shells trajectories for ultra fast fMRI.
AB  - MR-encephalography is a technique that allows real-time observation of functional
      changes in the brain with a time-resolution of 100 ms. The high sampling rate is
      enabled by the use of undersampled image acquisition with regularized
      reconstruction. The article describes a novel imaging method for fast three
      dimensional-MR-encephalography whole brain coverage based on undersampled, single
      shot concentric shells trajectories and the use of multiple small receiver coils.
      The technique allows the observation of changes in blood oxygenation level
      dependent signal as a measure of brain physiology at very high temporal
      resolution.

PMID- 22131237
TI  - Chemical synthesis of ubiquitinated peptides with varying lengths and types of
      ubiquitin chains to explore the activity of deubiquitinases.

PMID- 22131238
TI  - Comparison of the efficacy of nifedipine and hydralazine in hypertensive crisis
      in pregnancy.
AB  - Intravenous hydralazine is a commonly administered arteriolar vasodilator that is
      effective for hypertensive emergencies associated with pregnancy. Oral nifedipine
      is an alternative in management of these patients. In this study the efficacy of
      nifedipine and hydralazine in pregnancy was compared in a group of Iranian
      patients. Fifty hypertensive pregnant women were enrolled in the study. A
      randomized clinical trial was performed, in which patients in two groups received
      intravenus hydralazine or oral nifedipine to achieve target blood pressure
      reduction. The primary outcomes measured were the time and doses required for
      desired blood pressure achievement. Secondary measures included urinary output
      and maternal and neonatal side effects. The time required for reduction in
      systolic and diastolic blood pressure was shorter for oral nifedipine group (24.0
      +/- 10.0 min) than intravenus Hydralazine group (34.8 +/- 18.8 min) (P <= 0.016).
      Less frequent doses were required with oral nifedipine (1.2 +/- 0.5) compared to
      intravenus hydralazine (2.1 +/- 1.0) (P <= 0.0005). There were no episodes of
      hypotension after hydralazine and one after nifedipine. Nifedipine and
      hydralazine are safe and effective antihypertensive drugs, showing a controlled
      and comparable blood pressure reduction in women with hypertensive emergencies in
      pregnancy. Both drugs reduce episodes of persistent severe hypertension.
      Considering pharmacokinetic properties of nifedipine such as rapid onset and long
      duration of action, the good oral bioavailability and less frequent side effects,
      it looks more preferable in hypertension emergencies of pregnancy than
      hydralazine.

PMID- 22131240
TI  - Anti-mullerian hormone as a predictive factor in assisted reproductive technique
      of polycystic ovary syndrome patients.
AB  - This study aimed to assess the relationship between the serum levels of anti
      mullerian hormone (AMH) and other hormonal markers and results of assisted
      reproductive techniques (ART) in polycystic ovary syndrome (PCOS) patients. This
      cohort study was conducted on 60 PCOS patients who were candidates for assisted
      reproductive techniques. In all patients the serum levels of AMH, follicle
      stimulating hormone (FSH) and luteinizing hormone (LH), estradiol (E2), free
      testosterone (fT), testosterone (T) and inhibin B were measured in the 3(rd) day
      of menstrual cycle. The relationship between serum level of measured hormonal
      markers with retrieved oocytes, mature oocytes, the number of transferred fetus
      and pregnancy rate were assessed. The cut-off value for the serum level of AMH
      and retrieved oocytes were determined. There was a significant direct correlation
      between the serum mullerian inhibiting substance (MIS) level with number of total
      picked up oocytes (r = 0.412), mature oocytes (r = 0.472) and embryo transfer (r
      = 0.291). There was a linear and significant correlation between inhibin B and
      fertilization (r = 0.283) Cut-off point for AMH level according to presence or
      absence of pregnancy was 4.8 ng/ml and it was not statistically significant (P =
      0.655). Area under curve (AUC) was 0.543. Cut-off point for MIS according to
      picked up oocytes was 2.7 ng/ml with area under the curve (ROC curve) of 0.724
      (CI = 0.591-0.831) (P = 0.002). Patients with PCOS who had AMH more than 2.7
      ng/ml, the number of retrieved oocytes (6 or more) was higher than MIS/AMH <2.7
      ng/ml (P = 0.002). As a marker of ovarian responsiveness to controlled ovarian
      hyperstimulation (COH) and despite a small sample size of our study, it is
      revealed that pretreatment MIS/AMH is highly associated with the number of mature
      oocytes retrieved during COH in PCOS women.

PMID- 22131239
TI  - Detection of human papillomavirus in squamous cell carcinoma of conjunctiva by
      nested PCR: a case control study in Iran.
AB  - Squamous-cell carcinoma (SCC) of the eye conjunctiva is a rare tumor. Its link
      with immune impairment suggests that infectious agents such as human
      papillomavirus (HPV) may be involved in the etiology of SCC. We conducted a case
      control study on 50 SCC cases (mean age: 65.2) and 50 age frequency-matched
      control patients with lesion-free, normal conjunctival biopsies (mean age: 63.8)
      obtained from the cancer registry archive at Pathology Department of Farabi Eye
      Hospital, Tehran University of Medical Sciences, Tehran, Iran, where SCC has
      become the most common conjunctival malignancy. MY/GP nested PCR was performed
      for HPV detection and E6/E7 consensus primers in combination of type specific
      primers were used in another nested PCR series for HPV typing. HPV DNA was
      detected in 46 of 50 samples of squamous cell carcinoma and none of the normal
      biopsies by nested PCR using primer sets of the HPV consensus L1 region (MY/GP).
      Subsequently, specimens from the 46 positive cases were subjected to specific
      PCR. Although 630bp amplicon was produced in 44 of 46 samples (E6/E7 primers),
      none of the specific HPV PCR reactions for HPV DNA type 16, 18, 31 or 33 resulted
      in the detection of HPV DNA in the 44 SCC specimens of the conjunctiva. Current
      results confirm the role of HPV in the etiology of conjunctival SCC. The absence
      of HPV 16, 18, 31 and 33 in conjunctival SCC in this study raise doubts about the
      role of genital types of HPV in conjunctival carcinomas.

PMID- 22131241
TI  - Relationship between Helicobacter pylori infection and chronic obstructive
      pulmonary disease.
AB  - There is some evidence indicating the role of Helicobacter pylori infection in
      pathogenesis of extragastrointestinal diseases including skin, vascular, and
      autoimmune disorders, as well as some respiratory diseases. The aim of this study
      was to investigate the association between H. pylori and chronic obstructive
      pulmonary disease (COPD). In a case-control study, 90 patients with COPD and 90
      age- and sex- matched control subjects were included. Serum samples were tested
      for anti-H. pylori and anti-CagA IgG by ELISA. A physician completed a
      questionnaire including demographic characteristics, habitual history, and
      spirometric findings for each patient. Of 90 patients with COPD 66 (51%) had
      mild, 31 (34.4%) moderate, and 13 (14.4%) sever disease. There was no significant
      association between H. pylori IgG seropositivity and COPD. Serum levels of anti
      CagA IgG were significantly higher in patients with COPD than in the control
      subjects (P < 0.001). No association was observed between H. pylori infection and
      severity of COPD. The results suggest that there is an association between CagA
      positive H. pylori infections and COPD. Further studies should be planned to
      investigate the potential pathogenic mechanisms that might underlie these
      associations.

PMID- 22131242
TI  - Relationship between exposure to industrial noise and serum lipid profile.
AB  - Aim of our study was to investigate the effects of exposure to industrial noise
      on serum lipid profile among workers who are exposed to noise at work. In a
      historical cohort study, we recruited 154 and 146 male workers as high and low
      level noise exposure groups respectively. We defined workers with at least one
      year exposure to noise level more than 90 dB as high exposure group, and those
      with exposure to less than 80 dB as low exposure group. Afterwards, in the
      fasting blood specimens of participants we measured serum Triglyceride (TG),
      total Cholesterol (TC), high and low density lipoprotein (HDL and LDL). Mean of
      TG, TC, HDL and LDL for low exposure group were 148, 189, 38 and 103 mg/dl and
      for high exposure group were 237, 189, 37 and 104 mg/dl respectively. Mean serum
      TG between two groups was different. Even after adjustment for age, BMI, smoking
      and work hours per week, serum TG among high exposure group was 89 mg/dl higher
      than low exposure group and this difference was statistically significant (P =
      0.00). There was no significant difference between two groups in TC, LDL and HDL
      levels. This study did not find a statistically significant relationship between
      exposure to noise and serum TC, LDL and HDL, but TG in two groups was different
      and this difference was statistically significant.

PMID- 22131243
TI  - Relationship between the pattern of coronary artery disease risk factors and
      lipid ratios with five groups of body mass index in 28566 healthy adults.
AB  - Pattern of the coronary artery disease (CAD) risk factors across body mass index
      (BMI) categories remains uncertain. There is a different threshold of obesity for
      increasing cardiovascular hazard across populations, accordingly recognition and
      management of obesity and overweight can guide better control of CAD epidemic in
      the national level. To determine the discrepancy in the prevalence of CAD risk
      factors across five BMI categories. A population based survey of 28566
      participants recruited to medical screening of taxi drivres in Tehran (MSTDT) was
      designed. According to a standardized protocol data on CAD risk factors were
      obtained by taking medical history, examination and laboratory tests. After
      adjustment for age, sex, literacy, smoking, systolic blood pressure (SBP),
      fasting blood sugar (FBS), and LDL-C/HDL-C ratio, these CAD risk factors of
      diastolic blood pressure (DBP)>90 mmHg, hypertriglyceridemia, high triglyceride/
      HDL-C ratio, hypercholesterolemia, and high cholesterol/HDL-C ratio were
      increased significantly across five incremental categories of BMI. Prevalence of
      DBP> 90 mmHg, hypertriglyceridemia, hyper cholesterolemia and ratios of
      cholesterol/ HDL-C and TG/HDL-C increased considerably across five groups of BMI.
      This pattern is different from previous research and our results endorsed more
      features of pattern of CAD risk factors across BMI categories.

PMID- 22131244
TI  - Relationship between arterial blood pressure and body mass index of school age
      children of southern region of Iran.
AB  - Despite an increasing prevalence of obesity and hypertension in young age, there
      is limited information on the contribution of body mass index (BMI) to blood
      pressure (BP) in these populations, especially in developing countries. This
      study examines the association between BMI and BP in four populations of school
      age children across southern region of Islamic republic of Iran.

PMID- 22131245
TI  - The evaluation of the relationship between serum calcium level and stylohyoid
      length in adults.
AB  - Elongation and calcification of the stylohyoid apparatus is probably related to
      Eagle's syndrome and may cause such symptoms as facial pain and dysphagia in
      patients. In the present study, the relationship between serum calcium level and
      stylohyoid apparatus length was studied in adults referring to the dental college
      of Yazd. This was a cross-sectional descriptive study on 50 adult patients above
      20 years old (28 men, and 22 women) referring to the radiology ward of the dental
      college. The stylohyoid ligaments were measured from the base of the skull to the
      bony tip of each appendix by panoramic radiograph. Mineralization of the
      ligaments more than 30 mm on the panoramic radiographs was considered abnormal.
      The serum calcium level of all patients was then measured. Data were analyzed by
      t-test and Pearson's correlation analysis. Mean length of the stylohyoid
      apparatus was 27.36 +/- 9.10 mm and was not related to age and sex. An elongation
      rate of 26% was obtained. The mean serum calcium level was 9.39 +/- 0.57 mg/dl
      and there was not a statistically significant difference in serum calcium level
      between various age groups and genders. There was no relationship between the
      length of the stylohyoid apparatus of each side and serum calcium concentrations
      in different age groups. It appears that the length of the stylohyoid apparatus
      is not related to serum calcium level within our patient population.

PMID- 22131246
TI  - Urinary beta2 microglobulin in workers exposed to arc welding fumes.
AB  - Welding is a process in which two or more metals are attached by the use of heat
      and, in some cases, pressure. Direct exposure and inhalation of welding fumes
      causes acute and chronic side effects in humans. Kidney damage is one of these
      important side effects. beta(2) microglobulin is an 11.8 kilodalton protein and
      levels increase in the case of some inflammatory and viral diseases, or kidney
      malfunction and autoimmune diseases. In this study measurements of beta(2)
      microglobulin were used as a criterion for assessing effects on the kidneys of
      workers exposed to welding fumes. The study population were electric arc welders
      in an industrial plant in Tehran, Iran. For control we selected workers who did
      not have any exposure to welding fumes. Both groups were selected on the basis of
      a questionnaire and the consideration of criteria for inclusion and exclusion. In
      the end 50 cases and 50 controls were chosen. A urine sample was collected from
      all participants and urinary pH was set to between 6-8 using NaOH (1M). Sample
      transportation to the laboratory complied with the related standards. The samples
      were assessed using the ORG 5BM kit. For quantitative assessment of beta(2)
      microglobulin we used the Enzyme-linked Immunosorbent Assay (ELISA) method. The
      ages of the welders ranged from 21 to 48 years (mean=30.5 +/- 5.9 yrs) and of
      controls from 23 to 56 years (mean=31.8 +/- 5.9 yrs). Mean employment duration
      was 7.86 +/- 5.01 years (range 2 to 27 years) for welders. Mean beta(2)
      microglobulin level was 0.10 +/- 0.096 MUg/ml in welders and 0.11 +/- 0.06 in
      controls. This difference was not statistically significant (P=0.381). In
      conclusion we don't find that exposure to electric arc welding fumes cause a
      significant change in urinary beta(2) microglobulin compared to the control
      group.

PMID- 22131247
TI  - Medical students' viewpoint regarding the integrated module of basal ganglia.
AB  - Integration is an important educational strategy in medical education.
      Considering this idea, the goal of the present study was to design and
      implementation of longitudinal and vertical integrated education of anatomy,
      physiology, pharmacology, neurology and neuropsychiatry subjects of brain's basal
      ganglia by a multidisciplinary team. Kern's approach to curriculum development
      was used. Participants were 20 medical students at basic science level who
      contribute in a 10 stations of pre-test exam at Medical School's Skill Lab. After
      the implementation of the module by a multidisciplinary team, post-test were
      done. A structured questionnaire was designed to assess student opinions about
      adequacy, usefulness of the module using a Likert scale with 5 categories ranging
      from "completely agreement" to "completely disagreement". The result of pre and
      post-test were also compared. Twenty questionnaires were completed, giving a
      77.63% satisfaction rate. Seventy-five percent of students found it useful and
      appropriate at basic science level. About fifty percent of students suggested the
      implementation of this module for other medical students. The score of post-test
      was significantly (14.52 +/- 0.47 vs 6.32 +/- 0.62, P < 0.05) higher than pre
      test results. The viewpoints of medical students were positive and they value the
      module highly. Since it is not easy to change the style we teach, these results
      suggest necessitate of supporting the faculty member's participation in these
      modules.

PMID- 22131248
TI  - Esophageal squamous cell carcinoma with pancreatic metastasis: a case report.
AB  - Malignant tumors of pancreas are usually primary neoplasms and pancreatic
      metastases are rare findings. We are reporting a case of squamous cell carcinoma
      (SCC) of the esophagus with pancreatic metastasis. A 59-year old woman was
      admitted with chief complaint of abdominal pain and mass. She was a known case of
      esophageal SCC since 4 years before when she had undergone transthoracic
      esophagectomy and cervical esophago-gastrostomy. In order to evaluate recent
      abdominal mass, CT scan was done which revealed septated cystic lesion in the
      body and the tail of the pancreas. Palliative resection of the tumor was
      performed and its histological study showed SCC compatible with her previously
      diagnosed esophageal cancer.

PMID- 22131249
TI  - A case report of cyclic neutropenia associated with pyoderma gangrenosum.
AB  - We present a 24-year-old female referred with non-healing wound of a few days
      duration on anterior aspect of her right foreleg. Biopsy of the wound was
      reported to be pyoderma gangrenosum on pathologic report. Further work up of the
      patient for high grade fever and occasional leukopenias revealed the diagnosis of
      cyclic neutropenia. Treatment with granulocyte colony-stimulating factor (G-CSF)
      resulted in patient's neutrophil counts correction and dramatic improvement in
      healing of her lower extremity wound.

PMID- 22131250
TI  - Superior mesenteric artery aneurysm in a patient with chronic abdominal pain.
AB  - Superior mesenteric artery (SMA) aneurysm is a rare disease. In this case report,
      we present a 32 years old woman who was admitted to our hospital with chronic
      abdominal pain. SMA aneurysm was diagnosed after radiological evaluation. The
      patient underwent ligation of the superior mesenteric artery aneurysm and
      remained well 12 months after the surgery.

PMID- 22131251
TI  - Reading aloud pseudohomophones in Italian: always an advantage.
AB  - In the present article, the lexical contribution to nonword reading was evaluated
      using Italian pseudohomophones that contained atypical letters or letter
      sequences. Pseudohomophones were read faster than orthographically matched
      nonwords in both mixed (Experiment 1) and pure (Experiment 2) lists; in addition,
      a base-word frequency effect was obtained in both conditions. The same
      pseudohomophone advantage was observed when nonwords without atypical letter
      sequences were mixed in the experimental list (Experiment 3 ), and it disappeared
      only in lexical decision, in which pseudohomophones were rejected as quickly as
      control nonwords. The pattern of results was explained by assuming that, due to
      their orthographic properties, the Italian pseudohomophones did not benefit from
      an orthographic lexical contribution and were mainly processed through the
      interaction system between the sublexical mechanisms and the phonological output
      lexicon.

PMID- 22131252
TI  - Contactless conductivity detection for electrophoretic microseparation
      techniques.
AB  - The technique of capacitively coupled contactless conductivity detection for
      electrophoretic separations is discussed. The position of the combination of the
      two techniques, which both rely on the control of the movement of ions in the
      electric field, is highlighted. A brief historical overview and an introduction
      into the fundamental mechanisms is also given, but this exploration focuses
      mainly on the unique aspects of the intimate interfacing between ionic conduction
      in the measuring cell and the electronic conduction in the electronic detector
      circuitry. The general scope of application of the method is discussed as well as
      the recently introduced use of hydrodynamic pumping, which is a special feature
      of capillary electrophoresis with contactless conductivity, not possible with the
      standard UV-detection method.

PMID- 22131253
TI  - Enhancing agricultural productivity and rural incomes through sustainable use of
      natural resources in the semi arid tropics.
AB  - BACKGROUND: A participatory watershed management approach is one of the tested,
      sustainable and eco-friendly options to upgrade rain-fed agriculture to meet
      growing food demand along with additional multiple benefits in terms of improving
      livelihoods, addressing equity issues and biodiversity concerns. RESULTS:
      Watershed interventions at study sites in Thailand (Tad Fa and Wang Chai) and
      India (Kothapally) effectively reduced runoff and the associated soil loss. Such
      interventions at Xiaoxincun (China) and Wang Chai improved groundwater recharging
      and availability. Enhanced productive transpiration increased rainwater use
      efficiency for crop production by 13-29% at Xiaoxincun; 13-160% at Lucheba
      (China), 32-37% at Tad Fa and 23-46% at Wang Chai and by two to five times at
      Kothapally. Watershed interventions increased significantly the additional net
      returns from crop production as compared with the pre-watershed intervention
      period. Increased water availability opened up options for crop diversification
      with high-value crops, including increased forage production and boosted
      livestock-based livelihoods. CONCLUSION: In dryland tropics, integrated watershed
      management approach enabled farmers to diversify the systems along with
      increasing agricultural productivity through increased water availability, while
      conserving the natural resource base. Household incomes increased substantially,
      leading to improved living and building the resilience of the community and
      natural resources.

PMID- 22131254
TI  - Computer-aided detection scheme for identification of hypoattenuation of acute
      stroke in unenhanced CT.
AB  - Our purpose in this study was to develop a computer-aided detection scheme for
      identification of hypoattenuation of acute stroke on unenhanced CT images to
      select patients for thrombolysis of acute stroke. This method is based on a z
      score mapping method. The algorithm of the developed method consisted of five
      main steps: anatomic standardization, calculation of the z-score with a normal
      reference database, extraction of candidate voxels for hypoattenuation, feature
      extraction, and classification. The territory of the middle cerebral artery was
      divided into ten specified regions, according to a visually quantitative CT
      scoring system, the Alberta Stroke Programme Early CT Score (ASPECTS) method.
      Each of the ASPECTS-defined regions was classified as hypoattenuation or
      normality by linear discriminate analysis. The method was applied to 26 patients
      who had hypoattenuation areas (<6 h). The performance of this scheme for
      classification of hypoattenuation was evaluated using a leave-one-case-out
      method. As a result, an average sensitivity of 89.7% and an average specificity
      of 85.2% for automatically classifying hypoattenuation regions in the lentiform
      nucleus and the insular regions were obtained, and the average accuracy for the
      classification of hypoattenuation per patient was 84.6% (range 55.6-100%). The
      newly developed method has the potential accurately to identify hypoattenuation
      of acute stroke in the ASPECTS-defined regions.

PMID- 22131255
TI  - Amplatzer Septal Occluder to treat iatrogenic cardiac perforations.
AB  - BACKGROUND: Iatrogenic free wall cardiac perforation is a rare but serious
      complication encountered during percutaneous cardiac procedures, which usually
      leads to tamponade and death. Septal occluder devices have been developed for
      sealing intracardiac shunts but may be also used in this emergency setting.
      METHODS AND RESULTS: We report a small series of five consecutive cases of
      iatrogenic heart perforations that were treated with implantation of Amplatzer
      Septal Occluders (ASO). In the first case, iatrogenic left ventricle (LV)
      perforation occurred during LV biopsy and could be closed up with a 4 mm ASO. In
      the second case, a 4 mm ASO was used for sealing of a right atrial perforation
      allocated to Port-a-Cath dislodgment. The third case happened during transseptal
      puncture for implantation of a TandemHeart bVAD device in a patient suffering
      cardiogenic shock and was treated by implantation of a 5 mm ASO. The fourth
      patient was transferred to our facilities for percutaneous closure of an acute
      post-infarct VSD after anteroseptal myocardial infarction. This procedure was
      complicated by perforation of the posterolateral free wall and led to the
      deployment of 12 mm ASO. The last patient suffered from free LV wall perforation
      during investigation of a severe aortic stenosis and was treated by implantation
      of 4 mm ASO. All patients were alive after 24 hrs but the last patient died
      during the in-hospital stay of a right ventricular infarction complicated by
      multiple organ failure. CONCLUSIONS: Percutaneous device occlusion of iatrogenic
      heart perforation seems to be a safe and efficient method to treat iatrogenic
      heart perforation. In order to perform this elegant method, it is however
      imperative not to prematurely withdraw the perforating catheter to maintain
      access to the hole for closure.

PMID- 22131256
TI  - SAR-reduced spin-echo-based Bloch-Siegert B(1)(+) mapping: BS-SE-BURST.
AB  - Fast and accurate B(1)(+) mapping is possible using phase-based Bloch-Siegert
      (BS) methods. Importantly, the off-resonant pulses needed for BS B(1)(+) mapping
      methods can easily be implemented in multiple MR sequences. BS-based B(1)(+)
      mapping has thus been introduced for gradient echo (BS-FLASH), spin-echo (BS-SE),
      and Carr, Purcell, Meiboom, Gill (CPMG)-based multi-SE and turbo-SE sequences.
      When using SE and multi-SE/turbo-SE-based BS sequences, however, the high
      intrinsic specific absorption rates must be considered in clinical situations.
      This study introduces a fast BS B(1)(+) mapping method based on a SE-BURST
      sequence (BS-SE-BURST). With SE-BURST sequences, multiple low-magnitude
      excitation pulses are applied prior to the refocusing pulse. Thus, multiple and
      different phase-encoded echoes can be acquired per excitation cycle. Compared
      with a SE sequence, this excitation strategy results in a similar signal-to-noise
      ratio (SNR) per unit time but with reduced specific absorption rate. The proposed
      BS-SE-BURST sequence was implemented on a conventional 3 T whole body MRI scanner
      and applied successfully.

PMID- 22131258
TI  - Functional analyses of RET mutations in Chinese Hirschsprung disease patients.
AB  - BACKGROUND: Hirschsprung disease (HSCR) is a congenital disease characterized by
      the absence of ganglion cells in various length of distal digestive tract. The
      rearranged during transfection gene (RET) is considered the major gene in HSCR.
      Although an increasing number of HSCR-associated RET coding sequence (CDS)
      mutations have been identified in recent years, not many have been investigated
      for functional consequence on the RET protein. METHODS AND RESULTS: We examined
      the functional implications of the de novo RET-CDS mutations V145G, Y483X,
      V636fsX1, and F961L that we first identified in sporadic Chinese patients with
      HSCR. The V145G disrupted RET glycosylation and F961L RET phosphorylation.
      Presumably, the truncation mutations would affect the translocation or the
      anchoring of the RET protein onto the cellular membrane. CONCLUSION: The study of
      RET-CDS mutations that appear de novo is essential not only for understanding the
      mechanistic of the disease but also for penetrance and recurrence risk
      estimations, being the ultimate goal for the improvement in disease management
      and counseling.

PMID- 22131260
TI  - Recent trends of nitrogen flow of typical agro-ecosystems in China--major
      problems and potential solutions.
AB  - BACKGROUND: To diagnose problems that threaten regional sustainability and to
      devise appropriate treatment measures in China's agro-ecosystems, a study was
      carried out to quantify the nitrogen (N) flow in China's typical agro-ecosystems
      and develop potential solutions to the increasing environmental N load. RESULTS:
      The analysis showed that owing to human activity in the agro-ecosystems of
      Changjiang River Basin the mean total input of anthropogenic reactive N (i.e.
      chemical fertiliser, atmospheric deposition and bio-N fixation) increased from
      4.41 * 10(9) kg-N in 1980 to 7.61 * 10(9) kg-N in 1990 and then to 1.43 * 10(10)
      kg-N in 2000, with chemical fertiliser N being the largest contributor to N load.
      Field investigation further showed that changes in human behaviour and rural
      urbanisation have caused rural communities to become more dependent on chemical
      fertilisers. In rural regions, around 4.17 kg-N of per capita annual potential N
      load as excrement was returned to farmlands and 1.38 kg-N directly discharged
      into river systems, while in urbanised regions, around 1.00 kg-N of per capita
      annual potential N load as excrement was returned to farmlands and 5.62 kg-N
      discharged into river systems in urban areas. CONCLUSION: The findings of the
      study suggest that human activities have significantly altered the N cycle in
      agro-ecosystems of China. With high population density and scarce per capita
      water resources, non-point source pollution from agro-ecosystems continues to put
      pressure on aquatic ecosystems. Increasing the rate of organic matter recycling
      and fertiliser efficiency with limited reliance on chemical fertilisers might
      yield tremendous environmental benefits.

PMID- 22131261
TI  - How attractive is the NHS to private providers?

PMID- 22131262
TI  - Unsafe surgery: make it zero.

PMID- 22131263
TI  - Public health experts predict NHS reforms could lead to "chaos".

PMID- 22131264
TI  - Resolution enhanced T1-insensitive steady-state imaging.
AB  - Resolution enhanced T(1)-insensitive steady-state imaging (RE-TOSSI) is a new MRI
      pulse sequence for the generation of rapid T(2) contrast with high spatial
      resolution. TOSSI provides T(2) contrast by using nonequally spaced inversion
      pulses throughout a balanced steady-state free precession (SSFP) acquisition. In
      RE-TOSSI, these energy and time intensive adiabatic inversion pulses and
      associated magnetization preparation are removed from TOSSI after acquisition of
      the data around the center of k-space. Magnetization evolution simulations
      demonstrate T(2) contrast in TOSSI as well as reduction in the widening of the
      point spread function width (by up to a factor of 4) to a near ideal case for RE
      TOSSI. Phantom experimentation is used to characterize and compare the contrast
      and spatial resolution properties of TOSSI, RE-TOSSI, balanced SSFP, Half-Fourier
      Acquisition Single-Shot Turbo Spin Echo (HASTE), and turbo spin echo and to
      optimize the fraction of k-space acquired using TOSSI. Comparison images in the
      abdomen and brain demonstrate similar contrast and improved spatial resolution in
      RE-TOSSI compared with TOSSI; comparison balanced SSFP, HASTE, and turbo spin
      echo images are provided. RE-TOSSI is capable of providing high spatial
      resolution T(2)-weighted images in 1 s or less per image.

PMID- 22131265
TI  - Ultrastructural changes in the ovary cells of engorged Rhipicephalus sanguineus
      female ticks treated with esters of ricinoleic acid from castor oil (Ricinus
      communis).
AB  - Rhipicephalus sanguineus is a widely distributed tick species that has adapted to
      the urban environment, and the dog is its main host. This species is also known
      as a vector and reservoir of diseases caused by bacteria, protozoa, and viruses.
      Currently, acaricides of synthetic chemical origin have been widely and
      indiscriminately used, leading to the development of resistance to these products
      by ticks and causing damage to the environment. Thus, these issues have made it
      necessary to seek other forms of controlling these ectoparasites. R. sanguineus
      was artificially infested in host New Zealand White rabbits, which were divided
      into four treatment groups: control (CG1 and CG2) and treatment (TG1 and TG2)
      groups. TG1 and TG2 hosts were provided with feed supplemented with esters of
      ricinoleic acid from castor oil at a concentration of 5 g/kg of feed for 7 and 15
      days. Afterward, the ovaries of the female ticks were removed for analysis by
      transmission electron microscopy. The results showed ultrastructural changes in
      the somatic and germ cells of ovaries from TG1 and TG2 females, particularly with
      respect to chorion deposition, a protective membrane of the oocyte, as well as in
      the transport process of vitellogenic materials via the hemolymph and pedicel
      cells. Moreover, the mitochondria were less electron-dense and had cristae that
      were more disorganized than the mitochondria from CG1 and CG2 individuals. Thus,
      this study demonstrated the action of esters on the ovaries of R. sanguineus,
      signaling the prospect of a way to control this ectoparasite without affecting
      nontarget organisms or the environment.

PMID- 22131266
TI  - Macrocyclic restriction with flexible alkylene linkers: a simple strategy to
      control the solid-state properties of pi-conjugated systems.

PMID- 22131267
TI  - Ochratoxigenic moulds and effectiveness of grape field antifungals in a climatic
      change scenario.
AB  - BACKGROUND: The presence of ochratoxin A (OTA) in grapes and grape derivatives
      has been reported mainly in the Mediterranean area. Consequently, great efforts
      are being made to prevent the growth of Aspergillus on grapes. However, the
      European Commission suggests that climate change may result in increased
      temperatures and longer drought periods in southern Europe. Therefore the aim of
      this study was to investigate how ochratoxigenic fungal growth and the efficiency
      of fungicides used at present might be affected by environmental conditions
      predicted with climate change. RESULTS: The effectiveness of grape field
      antifungals (Switch, Flint Max and Equisetum arvense extract) under two
      alternating temperature, photoperiod and relative humidity (RH) scenarios
      (current: 20/30  degrees C, 16 h light/8 h darkness, 80% RH; predicted: 25/37 
      degrees C, 16 h light/8 h darkness, 75% RH) on the growth and OTA production of
      two Aspergillus carbonarius isolates and one Aspergillus ochraceus isolate on
      grapes was investigated. CONCLUSION: Predicted conditions reduced A. carbonarius
      and limited A. ochraceus growth. Antifungals reduced fungal infection (by 40
      84%), although no correlation between climatic conditions and effectiveness of
      the antifungals was found. However, Switch always showed the greatest reduction
      and E. arvense (0.02 g mL(-1) extract) the least. Higher temperatures affected
      OTA production by the isolates in different ways. In general, Switch and Flint
      Max reduced OTA production, while E. arvense stimulated it.

PMID- 22131268
TI  - Mice expressing T4826I-RYR1 are viable but exhibit sex- and genotype-dependent
      susceptibility to malignant hyperthermia and muscle damage.
AB  - Mutation T4825I in the type 1 ryanodine receptor (RYR1(T4825I/+)) confers human
      malignant hyperthermia susceptibility (MHS). We report a knock-in mouse line that
      expresses the isogenetic mutation T4826I. Heterozygous RYR1(T4826I/+) (Het) or
      homozygous RYR1(T4826I/T4826I) (Hom) mice are fully viable under typical rearing
      conditions but exhibit genotype- and sex-dependent susceptibility to
      environmental conditions that trigger MH. Hom mice maintain higher core
      temperatures than WT in the home cage, have chronically elevated
      myoplasmic[Ca(2+)](rest), and present muscle damage in soleus with a strong sex
      bias. Mice subjected to heat stress in an enclosed 37 degrees C chamber fail to
      trigger MH regardless of genotype, whereas heat stress at 41 degrees C invariably
      triggers fulminant MH in Hom, but not Het, mice within 20 min. WT and Het female
      mice fail to maintain euthermic body temperature when placed atop a bed whose
      surface is 37 degrees C during halothane anesthesia (1.75%) and have no
      hyperthermic response, whereas 100% Hom mice of either sex and 17% of the Het
      males develop fulminant MH. WT mice placed on a 41 degrees C bed maintain body
      temperature while being administered halothane, and 40% of the Het females and
      100% of the Het males develop fulminant MH within 40 min. Myopathic alterations
      in soleus were apparent by 12 mo, including abnormally distributed and enlarged
      mitochondria, deeply infolded sarcolemma, and frequent Z-line streaming regions,
      which were more severe in males. These data demonstrate that an MHS mutation
      within the S4-S5 cytoplasmic linker of RYR1 confers genotype- and sex-dependent
      susceptibility to pharmacological and environmental stressors that trigger
      fulminant MH and promote myopathy.

PMID- 22131269
TI  - Inhibition of fetal bone development through epigenetic down-regulation of HoxA10
      in obese rats fed high-fat diet.
AB  - Epidemiological studies show that maternal obesity during intrauterine and early
      postnatal life increases the risk of low bone mass and fracture later in life.
      Here, we show that bone development is inhibited in gestational embryonic day
      18.5 (E18.5) embryos from rat dams made obese by feeding a high-fat diet (HFD).
      Moreover, fetal rat osteogenic calvarial cells (FOCCs) from these obese dams have
      significantly less potential to develop into mature osteoblasts compared to cells
      from AIN-93G diet-fed controls. Profiling of transcriptional genes for
      osteogenesis revealed a profound decrease in the homeodomain-containing factor
      A10 (HoxA10) in FOCCs from fetuses of HFD-induced obese dams. Significant
      methylation of the HoxA10 promoter was found in those FOCCs, as well as in mouse
      ST2 cells treated with a mixture of free fatty acids similar to that found in
      serum from HFD-induced obese rats. This was accompanied by lower expression of
      osteogenic markers, but higher levels of PPARgamma. Control FOCCs depleted of the
      HoxA10 gene (shRNA) ex vivo behave similarly to cells from fetuses of obese dams;
      conversely, overexpression of HoxA10 gene in FOCCs from HFD rats exhibit the same
      phenotype as controls. Treatment of FOCCs from control rats or of ST2 cells with
      an artificial mixture of free fatty acids significantly down-regulated HoxA10
      protein expression, and cells exhibited adipocyte-like properties. These results
      suggest that maternal obesity impairs fetal skeletal development through down
      regulation of the HoxA10 gene, which may lead to an increase in the prevalence of
      low bone mass in the offspring later in life.

PMID- 22131270
TI  - Transcriptional regulation of the human FPR2/ALX gene: evidence of a heritable
      genetic variant that impairs promoter activity.
AB  - Lipoxin (LX) A(4,) a main endogenous stop-signal of inflammation, activates the G
      protein-coupled receptor FPR2/ALX, which triggers potent anti-inflammatory
      signaling in vivo. Thus, the regulation of FPR2/ALX expression may have
      pathophysiological and therapeutic relevance. Here, we mapped a nucleotide
      sequence with strong FPR2/ALX promoter activity. Chromatin immunoprecipitation
      revealed specificity protein 1 (Sp1) binding to the core promoter. Site-directed
      mutagenesis of the Sp1 cis-acting element and Sp1 overexpression established that
      this transcription factor is key for maximal promoter activity, which is instead
      suppressed by DNA methylation. LXA(4) enhanced FPR2/ALX promoter activity (+74%)
      and mRNA expression (+87.5%) in MDA-MB231 cells. A single nucleotide mutation
      (A/G) was detected in the core promoter of one subject with history of
      cardiovascular disease and of his two daughters. This mutation reduced by ~35-90%
      the promoter activity in vitro. Moreover, neutrophils from individuals carrying
      the A/G variant displayed ~10- and 3-fold reduction in FPR2/ALX mRNA and protein,
      respectively, compared with cells from their relatives or healthy volunteers
      expressing the wild-type allele. These results uncover FPR2/ALX transcriptional
      regulation and provide the first evidence of mutations that affect FPR2/ALX
      transcription, thus opening new opportunities for the understanding of the LXA(4)
      FPR2/ALX axis in human disease.

PMID- 22131271
TI  - The cysteinyl leukotriene 2 receptor mediates retinal edema and pathological
      neovascularization in a murine model of oxygen-induced retinopathy.
AB  - Leukotrienes have been implicated in the pathogenesis of degenerative diabetic
      retinopathy, with research focusing primarily on leukotriene B(4), with little
      attention devoted to the cysteinyl leukotrienes (cysLTs), which act through cysLT
      receptors (CysLT(1)R and CysLT(2)R). We demonstrate here the presence of
      CysLT(2)R in pericytes and endothelial cells of superficial retinal vasculature
      using an indirect assay by assessment of beta-galactosidase expression in
      CysLT(2)R-knockout (KO) mice. Retinal damage was induced in KO and wild-type (WT)
      mice using an established oxygen-induced retinopathy (OIR) model. CysLT(2)R
      expression following OIR was intensely up-regulated compared to sham-treated
      controls. Staining with Griffonia simplicifolia lectin revealed enhanced tissue
      damage (as assessed by vasoobliteration/vasoproliferation) in KO mice compared to
      WT controls, yet the opposite was true with respect to retinal edema. However,
      vascular endothelial growth factor receptor 1 (VEGFR1) transcripts were increased
      by OIR similarly with respect to genotype. Intravitreal application of exogenous
      cysLTs elicited greater vasculature leakage (assessed ex vivo) in eyes from WT
      mice compared to KO mice. While mRNA encoding enzymes for various components of
      the leukotriene cascade were detected in sham- and OIR-treated retinas, only
      prostaglandins and hydroxyeicosatetraenoic acids, but not leukotrienes, were
      detected in A23187-treated retina preparations. Together, these results implicate
      the CysLT(2)R in the progression of ischemic retinopathy.

PMID- 22131272
TI  - Fibrodysplasia ossificans progressiva: middle-age onset of heterotopic
      ossification from a unique missense mutation (c.974G>C, p.G325A) in ACVR1.
AB  - Fibrodysplasia ossificans progressiva (FOP) is the rare mendelian disease
      characterized by congenital malformation of the great toes preceding heterotopic
      ossification (HO) and caused by heterozygous activating mutation of the ACVR1
      gene, which encodes the ALK2 receptor for bone morphogenetic proteins. Early
      adult life is the latest reported presentation for the HO of FOP. The patient of
      our report first developed HO from FOP at 47 years of age. She had congenital
      hallux valgus deformity but despite various traumas was previously well. HO began
      several months after a brief, seemingly viral, illness. Sudden and progressive
      pain, redness, warmth, and swelling appeared over a scapula. Computed tomography
      was remarkable for asymmetrical thickening of muscles and fascial planes. At
      first, the significance of the great toe abnormalities went unrecognized
      elsewhere, and biopsy for suspected inflammatory fasciitis revealed proliferating
      fibroblasts with scattered inflammatory cells. Prednisone improved her symptoms
      but, when tapered, swellings developed on her chest, posterior thorax, and flank,
      and FOP was diagnosed. Methylprednisolone, methotrexate, and alendronate seemed
      to help her symptoms, but the lesions worsened and HO appeared and rapidly
      progressed. Mutation analysis of the ACVR1 gene revealed heterozygosity for a
      unique missense defect (c.974G>C, p.G325A) that predicted a conservative (mild)
      amino acid change within the kinase domain of ALK2. Hence, HO in FOP can be
      delayed until middle-age, and perhaps provoked by a viral illness. Nevertheless,
      progression of HO can then be rapid despite bisphosphonate and high-dose
      immunosuppressive therapy. Possibly, our patient's late-onset HO reflects her
      mild alteration of ALK2 or some protective and therapeutically useful genetic,
      epigenetic, or nongenetic factor. Recognition of presymptomatic individuals or
      late-onset HO in FOP should have these patients avoid traumas, treatments, and
      maybe viral illnesses that can initiate or exacerbate the HO. If the diagnosis of
      FOP is unclear, ACVR1 mutation analysis is available at certified laboratories.

PMID- 22131274
TI  - Erosion effects on chemical composition and morphology of dental materials and
      root dentin.
AB  - PURPOSE: This work aims to study the erosion on restorative materials and on
      surrounding dentin. Fifty root dentin samples were obtained from bovine incisors.
      METHODS: Twenty samples were not restored and thirty received cavity
      preparations. Samples were assigned to five groups: G1, G2: sound dentin (D); G3:
      composite resin (CR); G4: resin-modified glass-ionomer cement (RMGIC); G5: glass
      ionomer cement (GIC). The samples of groups 2-5 were submitted to six cycles
      (demineralization-remineralization). Samples were analyzed by micro energy
      dispersive X-ray fluorescence spectrometry (MU-EDXRF) and by scanning electron
      microscopy (SEM). RESULTS: Mineral loss was greater in G2 samples than in RMGI >
      CR > GIC > D (control). SEM images showed pronounced dentin demineralization in
      groups 2 and 4. The acid erosion has a significant effect on mineral loss (Ca and
      P) of root dentin without restoration. CONCLUSIONS: Composite resin had the best
      chemical resistance to erosion among all the materials. Fluoride contained in GIC
      seemed to cause some protection, however, with material degradation. Chemical
      interaction of tooth-colored dental materials with root dentin could be assessed
      by MU-EDXRF.

PMID- 22131273
TI  - The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter
      disease.
AB  - Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with
      potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22
      myotonic dystrophy type 2 clinically and neuropsychologically well-characterized
      patients and a corresponding healthy control group using structural brain
      magnetic resonance imaging at 3 T (T(1)/T(2)/diffusion-weighted). Voxel-based
      morphometry and diffusion tensor imaging with tract-based spatial statistics were
      applied for voxel-wise analysis of cerebral grey and white matter affection
      (P(corrected) < 0.05). We further examined the association of structural brain
      changes with clinical and neuropsychological data. White matter lesions rated
      visually were more prevalent and severe in myotonic dystrophy type 1 compared
      with controls, with frontal white matter most prominently affected in both
      disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel
      based morphometry analyses demonstrated extensive white matter involvement in all
      cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and
      2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted
      to myotonic dystrophy type 1. Accordingly, we found more prominent white matter
      affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by
      diffusion tensor imaging. Association fibres throughout the whole brain, limbic
      system fibre tracts, the callosal body and projection fibres (e.g.
      internal/external capsules) were affected in myotonic dystrophy types 1 and 2.
      Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We
      found mild executive and attentional deficits in our patients when
      neuropsychological tests were corrected for manual motor dysfunctioning.
      Regression analyses revealed associations of white matter affection with several
      clinical parameters in both disease entities, but not with neuropsychological
      performance. We showed that depressed mood and fatigue were more prominent in
      patients with myotonic dystrophy type 1 with less white matter affection (early
      disease stages), contrary to patients with myotonic dystrophy type 2. Thus,
      depression in myotonic dystrophies might be a reactive adjustment disorder rather
      than a direct consequence of structural brain damage. Associations of white
      matter affection with age/disease duration as well as patterns of cerebral water
      diffusion parameters pointed towards an ongoing process of myelin destruction
      and/or axonal loss in our cross-sectional study design. Our data suggest that
      both myotonic dystrophy types 1 and 2 are serious white matter diseases with
      prominent callosal body and limbic system affection. White matter changes
      dominated the extent of grey matter changes, which might argue against Wallerian
      degeneration as the major cause of white matter affection in myotonic
      dystrophies.

PMID- 22131275
TI  - Octahedral Pd2+ coordination and ferromagnetic ordering in Pd(S2O7).

PMID- 22131276
TI  - gamma-Oryzanol, tocol and mineral compositions in different grain fractions of
      giant embryo rice mutants.
AB  - BACKGROUND: Rice embryo is concentrated with lipid, protein and some bioactive
      chemicals. Two rice mutants IR64-GE and TNG71-GE (M7 generation) were
      characterised by an enlarged embryo compared with their wild types. In the
      present study, distributions of protein, lipid, total phenolics, gamma-oryzanol,
      tocols and some essential minerals in these two giant embryo mutants and their
      respective normal embryo wild types IR64 and TNG71 were compared. RESULTS: The
      embryo dry weights of giant embryo mutants IR64-GE and TNG71-GE were 0.92 and
      1.32 mg per seed respectively. These values were higher than those of their
      respective normal embryo genotypes (0.50 and 0.62 mg per seed). Large variations
      in protein, lipid, phenolic, gamma-oryzanol, tocol and minerals levels were found
      between mutant and wild-type pairs. The brown rice of TNG71-GE had higher total
      gamma-oryzanol (average of 24% increase) and total tocol (average of 75%
      increase) levels than TNG71, IR64 and IR64-GE. CONCLUSION: The embryo and bran
      parts of giant embryo mutant TNG71-GE were found to be good sources of vitamin E
      and gamma-oryzanol. Therefore it could be used to produce high-value by-products
      from milled embryo and bran parts and as a genetic resource for rice improvement
      programmes. TNG71-GE can also be used as a nutrient-fortified rice cultivar.

PMID- 22131279
TI  - Preparation of high-quality ultrathin transmission electron microscopy specimens
      of a nanocrystalline metallic powder.
AB  - This article explores the achievable transmission electron microscopy specimen
      thickness and quality by using three different preparation methods in the case of
      a high-strength nanocrystalline Cu-Nb powder alloy. Low specimen thickness is
      essential for spatially resolved analyses of the grains in nanocrystalline
      materials. We have found that single-sided as well as double-sided low-angle Ar
      ion milling of the Cu-Nb powders embedded into epoxy resin produced wedge-shaped
      particles of very low thickness (<10 nm) near the edge. By means of a modified
      focused ion beam lift-out technique generating holes in the lamella interior
      large micrometer-sized electron-transparent regions were obtained. However, this
      lamella displayed a higher thickness at the rim of >=30 nm. Limiting factors for
      the observed thicknesses are discussed including ion damage depths,
      backscattering, and surface roughness, which depend on ion type, energy, current
      density, and specimen motion. Finally, sections cut by ultramicrotomy at low
      stroke rate and low set thickness offered vast, several tens of square
      micrometers uniformly thin regions of ~10-nm minimum thickness. As major
      drawbacks, we have detected a thin coating on the sections consisting of epoxy
      deployed as the embedding material and considerable nanoscale thickness
      variations.

PMID- 22131280
TI  - Cyclization by catalytic ruthenium carbene insertion into C(sp3)-H bonds.

PMID- 22131283
TI  - Thermal breakdown of ZnTe nanowires.
AB  - As the applications for inorganic nanowires continuously grow, studies on the
      stability of these structures under high electrical/thermal stress conditions are
      needed. ZnTe nanowires are grown by the vapor-liquid-solid technique and their
      breakdown under Joule heating is studied through in situ monitoring in a
      transmission electron microscope (TEM). The experimental setup, consisting of a
      scanning tunneling microscope (STM) and a movable piezotube inside the TEM,
      allows the manipulation of a single nanowire. A voltage applied to the STM tip in
      contact with a ZnTe nanowire leads to the breakdown of the nanowire into Zn and
      Te particles or balls which is observed in real time. These balls grow by Ostwald
      ripening, rendering the surface morphology of the ZnTe nanowire progressively
      rough. Diffraction patterns along the stem of the wire after the partial
      breakdown showed substantially smaller lattice spacing compared to 0.35 nm for
      pristine ZnTe nanowires.

PMID- 22131281
TI  - Deletion of aquaporin-4 changes the perivascular glial protein scaffold without
      disrupting the brain endothelial barrier.
AB  - Expression of the water channel aquaporin-4 (AQP4) at the blood-brain interface
      is dependent upon the dystrophin associated protein complex. Here we investigated
      whether deletion of the Aqp4 gene affects the molecular composition of this
      protein scaffold and the integrity of the blood-brain barrier. High-resolution
      immunogold cytochemistry revealed that perivascular expression of alpha
      syntrophin was reduced by 60% in Aqp4(-/-) mice. Additionally, perivascular AQP4
      expression was reduced by 88% in alpha-syn(-/-) mice, in accordance with earlier
      reports. Immunofluorescence showed that Aqp4 deletion also caused a modest
      reduction in perivascular dystrophin, whereas beta-dystroglycan labeling was
      unaltered. Perivascular microglia were devoid of AQP4 immunoreactivity. Deletion
      of Aqp4 did not alter the ultrastructure of capillary endothelial cells, the
      expression of tight junction proteins (claudin-5, occludin, and zonula occludens
      1), or the vascular permeability to horseradish peroxidase and Evans blue albumin
      dye. We conclude that Aqp4 deletion reduces the expression of perivascular glial
      scaffolding proteins without affecting the endothelial barrier. Our data also
      indicate that AQP4 and alpha-syntrophin are mutually dependent upon each other
      for proper perivascular expression.

PMID- 22131284
TI  - Residual woody biomass torrefaction: challenges and opportunities for the waste
      management sector.

PMID- 22131285
TI  - Morphology and morphometry of the reproductive system of female Saguinus midas
      (Linnaeus, 1758).
AB  - In this article, the reproductive system's morphology of three young animals of
      the species Saguinus midas, from the bauxite mine in Paragominas, is described.
      The specimens were fixed and preserved in a solution of 10% aqueous formaldehyde,
      followed by dissection, measurement of the genital organs (uterus, vagina,
      ovaries, and uterine tubes), and histological processing. The vulva is delimited
      by the labia, with a clitoris. It is lined by keratinized stratified squamous
      epithelium with sebaceous glands of holocrine secretion. The vagina is an
      elongated tube with an average length of 26 mm and diameter of 1 mm, presenting a
      non-keratinized squamous epithelium, disposed between the vestibule of the vagina
      and cervix, the latter being relatively short. The uterus is simple, has globular
      shape and is located in the caudal portion of the abdominal cavity, with an
      average length of 14 mm and average width of 7 mm. It is formed by vascular and
      serous layers of muscles, and undergoes a bifurcation to form two structures on
      the bottom of blind sac. The uterine tubes are long and convoluted with an
      average length of 35 mm (right) and 36 mm (left), consisting of loose connective
      tissue and muscle layer lined by simple ciliated columnar epithelium. The ovaries
      are large and ellipsoid with smooth surface. Histologically, one animal showed
      ovulation fosse.

PMID- 22131286
TI  - Connexin 32 is involved in mitosis.
AB  - The X-linked form of Charcot-Marie-Tooth disorder (CMTX) is the second most
      frequent type (15% of CMT forms). It involves the GJB1 gene coding for connexin
      32, a protein involved in gap junction formation and function. There is no
      curative treatment for CMTX. We present data on transgenic lines that was
      accomplished by inserting a human BAC carrying the GJB1 gene, in which two
      different mutations in connexin 32 (Cx32) observed in patients were introduced.
      Investigation of these models implicated Cx32 in the control of mitotic
      stability. The model in which Gjb1 has been invalidated had the same phenotype.
      This new function for Cx32 was recently confirmed by results from the Mitocheck
      program. Locomotor impediment was seen in the behavior of these animals, the
      severity of which correlated with transgene copy number and RNA expression.

PMID- 22131287
TI  - On the use of big-bang method to generate low-energy structures of atomic
      clusters modeled with pair potentials of different ranges.
AB  - The efficiency of the so-called big-bang method for the optimization of atomic
      clusters is analysed in detail for Morse pair potentials with different ranges;
      here, we have used Morse potentials with four different ranges, from long- rho =
      3) to short-ranged rho = 14) interactions. Specifically, we study the efficacy of
      the method in discovering low-energy structures, including the putative global
      minimum, as a function of the potential range and the cluster size. A new global
      minimum structure for long-ranged rho = 3) Morse potential at the cluster size of
      n= 240 is reported. The present results are useful to assess the maximum cluster
      size for each type of interaction where the global minimum can be discovered with
      a limited number of big-bang trials.

PMID- 22131288
TI  - Composite of TiN nanoparticles and few-walled carbon nanotubes and its
      application to the electrocatalytic oxygen reduction reaction.

PMID- 22131289
TI  - Morphological characterization of the progenitor blood cells in canine and feline
      umbilical cord.
AB  - The umbilical cord blood (UCB) is an important source of hematopoietic stem cells
      with great deal of interest in regenerative medicine. The UCB cells have been
      extensively studied as an alternative to the bone marrow transplants. The
      challenge is to define specific methods to purify and characterize these cells in
      different animal species. This study is aimed at morphological characterization
      of progenitor cells derived from UCB highlighting relevant differences with
      peripheral blood of adult in dog and cats. Therefore, blood was collected from 18
      dogs and 5 cats' umbilical cords from fetus in various developmental stages. The
      mononuclear cells were separated using the gradient of density Histopaque-1077.
      Characterization of CD34+ cells was performed by flow cytometric analysis and
      transmission electron microscopy. Granulocytes (ancestry of the basophiles,
      eosinophiles, and neutrophiles) and agranulocytes (represented by immature
      lymphocytes) were identified. We showed for the first time the ultrastructural
      features of cat UCB cells.

PMID- 22131290
TI  - Nocturnal temperature controlled laminar airflow for treating atopic asthma: a
      randomised controlled trial.
AB  - OBJECTIVE: To determine whether environmental control using nocturnal temperature
      controlled laminar airflow (TLA) treatment could improve the quality of life of
      patients with persistent atopic asthma. DESIGN: Randomised, double-blind, placebo
      controlled, parallel-group trial. Setting Nineteen European asthma clinics.
      PARTICIPANTS: 312 patients aged 7-70 with inadequately controlled persistent
      atopic asthma. MAIN OUTCOME MEASURE: Proportion of patients with an increase of
      >=0.5 points in asthma quality of life score after 1 year of treatment. RESULTS:
      TLA devices were successfully installed in the bedrooms of 282 (90%) patients
      included in the primary efficacy analysis. There was a difference in treatment
      response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%)
      groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02).3 In patients aged >=12, on
      whom the study was powered, the difference in response rate was similar-active
      106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7,
      p=0.059). There was a difference between groups in fractional exhaled nitric
      oxide change of -7.1 ppb (-13.6 to -0.7, p=0.03). Active treatment was associated
      with less increase in cat-specific IgE than placebo. There was no difference in
      adverse event rates between treatment groups. CONCLUSION: Inhalant exposure
      reduction with TLA improves quality of life, airway inflammation and systemic
      allergy in patients with persistent atopic asthma. TLA may be a treatment option
      for patients with inadequately controlled persistent atopic asthma. Trial
      registration number Clinical Trials NCT00986323.

PMID- 22131291
TI  - Disengagement coping as a mediator between trauma-related guilt and PTSD
      severity.
AB  - This study examined disengagement coping as a partial mediator between trauma
      related guilt and severity of posttraumatic stress disorder (PTSD) in a sample of
      veterans (N = 175) entering residential PTSD treatment with either PTSD or
      subthreshold PTSD. Disengagement coping partially mediated the relationship
      between guilt and self-reported PTSD severity (b = .07; 95% CI = [-.003, .13]; p
      = .06), but did not mediate the relationship when PTSD severity was based on
      clinicians' ratings. These findings bolster Street, Gibson, and Holohan's (2005)
      contention that higher guilt-related cognitions are related to increases in the
      use of disengagement coping strategies, which can interfere with PTSD recovery.
      The findings support the importance of PTSD treatments that target reductions in
      guilt-related cognitions and disengagement coping strategies.

PMID- 22131293
TI  - Feedback regulation of the alpha2(1) collagen gene via the Mek-Erk signaling
      pathway.
AB  - The extracellular matrix (ECM) provides the microenvironment that is pivotal for
      cell growth, motility, attachment, and differentiation. Advances in cell culture
      techniques have led to the development of cell-derived ECM model systems that are
      more reflective of the in vivo architecture of the ECM in tissue. In this study,
      a fibroblast-derived ECM (fd-ECM) was used to study the feedback regulation of
      type I collagen synthesis in fibroblasts. Fibroblasts plated on a preformed fd
      ECM showed a significant decrease in the production of type I collagen and pro
      alpha2(1) collagen mRNA compared to cells grown in the absence of a matrix.
      Function-blocking antibodies showed that this downregulation of type I collagen
      gene expression is mediated via alpha2beta1 integrin. The use of several kinase
      inhibitors and a dominant negative ras construct (N17Ras) showed that the matrix
      mediated downregulation of COL1A2 occurs via Ras-dependent activation of the
      MEK/ERK signaling pathway. Deletion analysis of the COL1A2 promoter implicated
      the region between -375 and -107 as containing a potential matrix responsive
      element. The use of Sp1 siRNA demonstrated that Sp1 is an important mediator of
      this feedback inhibition. This study provides some new insights into the feedback
      regulation of COL1A2 gene expression.

PMID- 22131292
TI  - Beyond DNA origami: the unfolding prospects of nucleic acid nanotechnology.
AB  - Nucleic acid nanotechnology exploits the programmable molecular recognition
      properties of natural and synthetic nucleic acids to assemble structures with
      nanometer-scale precision. In 2006, DNA origami transformed the field by
      providing a versatile platform for self-assembly of arbitrary shapes from one
      long DNA strand held in place by hundreds of short, site-specific (spatially
      addressable) DNA 'staples'. This revolutionary approach has led to the creation
      of a multitude of two-dimensional and three-dimensional scaffolds that form the
      basis for functional nanodevices. Not limited to nucleic acids, these nanodevices
      can incorporate other structural and functional materials, such as proteins and
      nanoparticles, making them broadly useful for current and future applications in
      emerging fields such as nanomedicine, nanoelectronics, and alternative energy.

PMID- 22131294
TI  - Debris and smear removal in flattened root canals after use of different irrigant
      agitation protocols.
AB  - Scanning electron microscopy (SEM) can be used to analyze the presence of debris
      and smear layer on the internal walls of root canal. This study evaluated the
      debris and smear removal in flattened root canals using SEM after use of
      different irrigant agitation protocols. Fifty mandibular incisors were
      distributed into five groups (n = 10) according to the irrigant agitation
      protocol used during chemomechanical preparation: conventional syringe irrigation
      with NaviTip needle (no activation), active scrubbing of irrigant with brush
      covered NaviTip FX needle, manual dynamic irrigation, continuous passive
      ultrasonic irrigation, and apical negative pressure irrigation (EndoVac system).
      Canals were irrigated with 5 mL of 2.5% NaOCl at each change of instrument and
      received a final flush with 17% EDTA for 1 min. After instrumentation, the roots
      were split longitudinally and SEM micrographs at *100 and *1,000 were taken to
      evaluate the amount of debris and smear layer, respectively, in each third. Data
      were analyzed by Kruskal-Wallis and Dunn's post-hoc tests (alpha = 5%). Manual
      dynamic activation left significantly (p < 0.05) more debris inside the canals
      than the other protocols, while ultrasonic irrigation and EndoVac were the most
      effective (p < 0.05) for debris removal. Regarding the removal of smear layer,
      there was no statistically significant difference (p > 0.05) either among the
      irrigant agitation protocols or between the protocol-canal third interactions.
      Although none of the irrigant agitation protocols completely removed debris and
      smear layer from flattened root canals, the machine-assisted agitation systems
      (ultrasound and EndoVac) removed more debris than the manual techniques.

PMID- 22131295
TI  - Health and safety implications of occupational exposure to engineered
      nanomaterials.
AB  - The rapid growth and commercialization of nanotechnology are currently outpacing
      health and safety recommendations for engineered nanomaterials. As the production
      and use of nanomaterials increase, so does the possibility that there will be
      exposure of workers and the public to these materials. This review provides a
      summary of current research and regulatory efforts related to occupational
      exposure and medical surveillance for the nanotechnology workforce, focusing on
      the most prevalent industrial nanomaterials currently moving through the
      research, development, and manufacturing pipelines. Their applications and usage
      precedes a discussion of occupational health and safety efforts, including
      exposure assessment, occupational health surveillance, and regulatory
      considerations for these nanomaterials.

PMID- 22131296
TI  - Steroid 5alpha-reductase in adult rat brain after neonatal testosterone
      administration.
AB  - Testosterone (T) plays an important role in developing brain, dictating sex
      specific behavior and physiology. 3alpha,5alpha-Reduced neurosteroids also
      regulate reproductive behavior. The key enzyme in the biosynthesis of these
      neurosteroids is 5alpha-reductase (5alpha-R), expressed as two isozymes, 5alpha
      R1 and 5alpha-R2. In this study, T and sesame oil (vehicle) were administered
      during postnatal sexual differentiation of the central nervous system (CNS) and
      mRNA levels of 5alpha-R isozymes, were measured using quantitative RT-PCR in
      prefrontal cortex of male and female rats with different androgenic status at
      adulthood. Our results indicate that T concentrations during postnatal sexual
      differentiation of the rat CNS, among other sex-dependent factors, influence
      brain levels of 5alpha-R isozymes in adulthood and the pattern of their
      regulation by androgen hormones.

PMID- 22131297
TI  - Auditory hallucinations: a review of assessment tools.
AB  - Auditory hallucinations are a common and troubling symptom in psychotic
      disorders. We aimed to identify measures that could be used by clinicians and
      researchers to assess the experience of auditory hallucinations. A literature
      review was conducted to identify auditory hallucination measures that were
      developed since the last such review in 1998. We identified 10 tools: eight self
      report measures and two clinical interviews. The scales measured diverse
      constructs and are divided into four categories for review: multidimensional
      assessment, coping strategies, rating of beliefs and acceptance or mindfulness.
      Evidence of the measures' reliability, validity and sensitivity to change are
      discussed. There has been an expansion in the range of instruments available,
      particularly in self-report questionnaires and in measures that focus on
      psychological aspects such as attitudes and beliefs regarding voices.

PMID- 22131298
TI  - Efficient Kernelized prototype based classification.
AB  - Prototype based classifiers are effective algorithms in modeling classification
      problems and have been applied in multiple domains. While many supervised
      learning algorithms have been successfully extended to kernels to improve the
      discrimination power by means of the kernel concept, prototype based classifiers
      are typically still used with Euclidean distance measures. Kernelized variants of
      prototype based classifiers are currently too complex to be applied for larger
      data sets. Here we propose an extension of Kernelized Generalized Learning Vector
      Quantization (KGLVQ) employing a sparsity and approximation technique to reduce
      the learning complexity. We provide generalization error bounds and experimental
      results on real world data, showing that the extended approach is comparable to
      SVM on different public data.

PMID- 22131299
TI  - Ranking-based kernels in applied biomedical diagnostics using a support vector
      machine.
AB  - This paper presents some essential findings and results on using ranking-based
      kernels for the analysis and utilization of high dimensional and noisy biomedical
      data in applied clinical diagnostics. We claim that presented kernels combined
      with a state-of-the-art classification technique - a Support Vector Machine (SVM)
      - could significantly improve the classification rate and predictive power of the
      wrapper method, e.g. SVM. Moreover, the advantage of such kernels could be
      potentially exploited for other kernel methods and essential computer-aided tasks
      such as novelty detection and clustering. Our experimental results and
      theoretical generalization bounds imply that ranking-based kernels outperform
      other traditionally employed SVM kernels on high dimensional biomedical and
      microarray data.

PMID- 22131300
TI  - Discovering significant evolution patterns from satellite image time series.
AB  - Satellite Image Time Series (SITS) provide us with precious information on land
      cover evolution. By studying these series of images we can both understand the
      changes of specific areas and discover global phenomena that spread over larger
      areas. Changes that can occur throughout the sensing time can spread over very
      long periods and may have different start time and end time depending on the
      location, which complicates the mining and the analysis of series of images. This
      work focuses on frequent sequential pattern mining (FSPM) methods, since this
      family of methods fits the above-mentioned issues. This family of methods
      consists of finding the most frequent evolution behaviors, and is actually able
      to extract long-term changes as well as short term ones, whenever the change may
      start and end. However, applying FSPM methods to SITS implies confronting two
      main challenges, related to the characteristics of SITS and the domain's
      constraints. First, satellite images associate multiple measures with a single
      pixel (the radiometric levels of different wavelengths corresponding to infra
      red, red, etc.), which makes the search space multi-dimensional and thus requires
      specific mining algorithms. Furthermore, the non evolving regions, which are the
      vast majority and overwhelm the evolving ones, challenge the discovery of these
      patterns. We propose a SITS mining framework that enables discovery of these
      patterns despite these constraints and characteristics. Our proposal is inspired
      from FSPM and provides a relevant visualization principle. Experiments carried
      out on 35 images sensed over 20 years show the proposed approach makes it
      possible to extract relevant evolution behaviors.

PMID- 22131301
TI  - Blood glucose level neural model for type 1 diabetes mellitus patients.
AB  - This paper deals with the blood glucose level modeling for Type 1 Diabetes
      Mellitus (T1DM) patients. The model is developed using a recurrent neural network
      trained with an extended Kalman filter based algorithm in order to develop an
      affine model, which captures the nonlinear behavior of the blood glucose
      metabolism. The goal is to derive a dynamical mathematical model for the T1DM as
      the response of a patient to meal and subcutaneous insulin infusion. Experimental
      data given by continuous glucose monitoring system is utilized for identification
      and for testing the applicability of the proposed scheme to T1DM subjects.

PMID- 22131302
TI  - The S(2)-Ensemble Fusion Algorithm.
AB  - This paper presents a novel model for performing classification and visualization
      of high-dimensional data by means of combining two enhancing techniques. The
      first is a semi-supervised learning, an extension of the supervised learning used
      to incorporate unlabeled information to the learning process. The second is an
      ensemble learning to replicate the analysis performed, followed by a fusion
      mechanism that yields as a combined result of previously performed analysis in
      order to improve the result of a single model. The proposed learning schema,
      termed S(2)-Ensemble, is applied to several unsupervised learning algorithms
      within the family of topology maps, such as the Self-Organizing Maps and the
      Neural Gas. This study also includes a thorough research of the characteristics
      of these novel schemes, by means quality measures, which allow a complete
      analysis of the resultant classifiers from the viewpoint of various perspectives
      over the different ways that these classifiers are used. The study conducts
      empirical evaluations and comparisons on various real-world datasets from the UCI
      repository, which exhibit different characteristics, so to enable an extensive
      selection of situations where the presented new algorithms can be applied.

PMID- 22131303
TI  - The monocarboxylate transporter family--Structure and functional
      characterization.
AB  - Monocarboxylate transporters (MCTs) catalyze the proton-linked transport of
      monocarboxylates such as L-lactate, pyruvate, and the ketone bodies across the
      plasma membrane. There are four isoforms, MCTs 1-4, which are known to perform
      this function in mammals, each with distinct substrate and inhibitor affinities.
      They are part of the larger SLC16 family of solute carriers, also known as the
      MCT family, which has 14 members in total, all sharing conserved sequence motifs.
      The family includes a high-affinity thyroid hormone transporter (MCT8), an
      aromatic amino acid transporter (T-type amino acid transporter 1/MCT10), and
      eight orphan members yet to be characterized. MCTs were predicted to have 12
      transmembrane helices (TMs) with intracellular C- and N-termini and a large
      intracellular loop between TMs 6 and 7, and this was confirmed by labeling
      studies and proteolytic digestion. Site-directed mutagenesis has identified key
      residues required for catalysis and inhibitor binding and enabled the development
      of a molecular model of MCT1 in both inward and outward facing conformations.
      This suggests a likely mechanism for the translocation cycle. Although MCT family
      members are not themselves glycosylated, MCTs1-4 require association with a
      glycosylated ancillary protein, either basigin or embigin, for their correct
      translocation to the plasma membrane. These ancillary proteins have a single
      transmembrane domain and two to three extracellular immunoglobulin domains. They
      must remain closely associated with MCTs1-4 to maintain transporter activity.
      MCT1, MCT3, and MCT4 bind preferentially to basigin and MCT2 to embigin. The
      choice of binding partner does not affect substrate specificity or kinetics but
      can influence inhibitor specificity.

PMID- 22131304
TI  - Localization of pain-related brain activation: a meta-analysis of neuroimaging
      data.
AB  - A meta-analysis of 140 neuroimaging studies was performed using the activation
      likelihood-estimate (ALE) method to explore the location and extent of activation
      in the brain in response to noxious stimuli in healthy volunteers. The first
      analysis involved the creation of a likelihood map illustrating brain activation
      common across studies using noxious stimuli. The left thalamus, right anterior
      cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior
      insula had the highest likelihood of being activated. The second analysis
      contrasted noxious cold with noxious heat stimulation and revealed higher
      likelihood of activation to noxious cold in the subgenual ACC and the amygdala.
      The third analysis assessed the implications of using either a warm stimulus or a
      resting baseline as the control condition to reveal activation attributed to
      noxious heat. Comparing noxious heat to warm stimulation led to peak ALE values
      that were restricted to cortical regions with known nociceptive input. The fourth
      analysis tested for a hemispheric dominance in pain processing and showed the
      importance of the right hemisphere, with the strongest ALE peaks and clusters
      found in the right insula and ACC. The fifth analysis compared noxious muscle
      with cutaneous stimuli and the former type was more likely to evoke activation in
      the posterior and anterior cingulate cortices, precuneus, dorsolateral prefrontal
      cortex, and cerebellum. In general, results indicate that some brain regions such
      as the thalamus, insula and ACC have a significant likelihood of activation
      regardless of the type of noxious stimuli, while other brain regions show a
      stimulus-specific likelihood of being activated.

PMID- 22131306
TI  - Hyperkinetic impulse disorder in children's behavior problems.

PMID- 22131307
TI  - Commentary on hyperkinetic impulse disorder.

PMID- 22131309
TI  - The many faces of the hairpin ribozyme: structural and functional variants of a
      small catalytic RNA.
AB  - The hairpin ribozyme is a small catalytic RNA that has been reengineered
      resulting in a number of variants with extended or even new functions. Thus,
      manipulation of the hairpin ribozyme structure has allowed for activity control
      by external effectors, namely oligonucleotides, flavine mononucleotide, and
      adenine. Hairpin ribozyme-derived twin ribozymes that mediate RNA fragment
      exchange reactions as well as self-processing hairpin ribozymes were designed.
      Furthermore, several hairpin ribozyme variants have been engineered for knock
      down of specific RNA substrates by adapting the substrate-binding domain to the
      specific target sequence. This review will focus on hairpin ribozymes possessing
      structural extensions/variations and thus functionally differing from the parent
      hairpin ribozyme.

PMID- 22131310
TI  - Generation and genetic stability of tick-borne encephalitis virus mutants
      dependent on processing by the foot-and-mouth disease virus 3C protease.
AB  - Mature protein C of tick-borne encephalitis virus (TBEV) is cleaved from the
      polyprotein precursor by the viral NS2B/3 protease (NS2B/3(pro)). We showed
      previously that replacement of the NS2B/3(pro) cleavage site at the C terminus of
      protein C by the foot-and-mouth disease virus (FMDV) 2A StopGo sequence leads to
      the production of infectious virions. Here, we show that infectious virions can
      also be produced from a TBEV mutant bearing an inactivated 2A sequence through
      the expression of the FMDV 3C protease (3C(pro)) either in cis or in trans (from
      a TBEV replicon). Cleavage at the C terminus of protein C depended on the
      catalytic activity of 3C(pro) as well as on the presence of an optimized 3C(pro)
      cleavage site. Passage of the TBEV mutants bearing a 3C(pro) cleavage site either
      in the absence of 3C(pro) or in the presence of a catalytically inactive 3C(pro)
      led to the appearance of revertants in which protein C cleavage by NS2B/3(pro)
      had been regained. In three different revertants, a cleavage site for
      NS2B/3(pro), namely RR*C, was now present, leading to an elongated protein C.
      Furthermore, two revertants acquired additional mutations in the C terminus of
      protein C, eliminating two basic residues. Although these latter mutants showed
      wild-type levels of early RNA synthesis, their foci were smaller and an
      accumulation of protein C in the cytoplasm was observed. These findings suggest a
      role of the positive charge of the C terminus of protein C for budding of the
      nucleocapsid and further support the notion that TBEV protein C is a
      multifunctional protein.

PMID- 22131311
TI  - A novel reassortant canine H3N1 influenza virus between pandemic H1N1 and canine
      H3N2 influenza viruses in Korea.
AB  - During recent canine influenza surveillance in South Korea, a novel H3N1 canine
      influenza virus (CIV) that is a putative reassortant between pandemic H1N1 2009
      and H3N2 CIVs was isolated. Genetic analysis of eight genes of the influenza
      virus revealed that the novel H3N1 isolate presented high similarities (99.1-99.9
      %) to pandemic influenza H1N1, except for in the haemagglutinin (HA) gene. The HA
      gene nucleotide sequence of the novel CIV H3N1 was similar (99.6 %) to that of
      CIV H3N2 isolated in Korea and China. Dogs infected with the novel H3N1 CIV did
      not show any notable symptoms, in contrast to dogs infected with H3N2 CIV.
      Despite no visible clinical signs of disease, nasal shedding of virus was
      detected and the infected dogs presented mild histopathological changes.

PMID- 22131312
TI  - Canine ASCT1 and ASCT2 are functional receptors for RD-114 virus in dogs.
AB  - All domestic cats carry an infectious endogenous retrovirus termed RD-114 virus.
      Recently, we and others found that several live-attenuated vaccines for dogs were
      contaminated with infectious RD-114 virus. In this study, we confirmed that the
      RD-114 virus efficiently infected and proliferated well in canine primary kidney
      cells, as well as three tested canine cell lines. Further, we identified canine
      ASCT1 and ASCT2, sodium-dependent neutral amino acid transporters, as RD-114
      virus receptors. Canine ASCT2 also acts as a functional receptor for simian
      retrovirus 2, a pathogenic retrovirus that induces immunodeficiency in rhesus
      macaques. Identification of the canine receptor for RD-114 virus will help in
      evaluating the risk from vaccines contaminated by the virus.

PMID- 22131313
TI  - The human submandibular gland: immunohistochemical analysis of SNAREs and
      cytoskeletal proteins.
AB  - Submandibular acinar glands secrete numerous proteins such as digestive enzymes
      and defense proteins on the basis of the exocrine secretion mode. Exocytosis is a
      complex process, including a soluble NSF attachment protein receptor (SNARE)
      mediated membrane fusion of vesicles and target membrane and the additional
      activation of cytoskeletal proteins. Relevant data are available predominantly
      for animal salivary glands, especially of the rat parotid acinar cells. The
      authors investigated the secretory molecular machinery of acinar (serous) cells
      in the human submandibular gland by immunohistochemistry and immunofluorescence
      and found diverse proteins associated with exocytosis for the first time. SNAP
      23, syntaxin-2, syntaxin-4, and VAMP-2 were localized at the luminal plasma
      membrane; syntaxin-2 and septin-2 were expressed in vesicles in the cytoplasm.
      Double staining of syntaxin-2 and septin-2 revealed a colocalization on the same
      vesicles. Lactoferrin and alpha-amylase served as a marker for secretory vesicles
      and were labeled positively together with syntaxin-2 and septin-2 in double
      staining procedures. Cytoskeletal components such as actin, myosin II, cofilin,
      and profilin are concentrated at the apical plasma membrane of acinar
      submandibular glands. These observations complement the understanding of the
      complex exocytosis mechanisms.

PMID- 22131314
TI  - The role of PPAR in myocardial response to ischemia in normal and diseased heart.
AB  - Peroxisome proliferator-activated receptors (PPAR), ligand-activated
      transcription factors, belong to the nuclear hormone receptor superfamily
      regulating expression of genes involved in different aspects of lipid metabolism,
      inflammation and cardiac energy production. Activation of PPAR-alpha isoform by
      its natural ligands, fatty acids (FA) and eicosanoids, promotes mitochondrial FA
      oxidation as the primary ATP-generating pathway. On the other hand, PPAR-gamma
      regulates lipid anabolism or storage, while, until recently, the function of PPAR
      beta/delta has been less explored. Under conditions associated with acute or
      chronic oxygen deprivation, PPAR-alpha modulates expression of genes that
      determine substrate switch (FA vs. glucose) aimed at maintenance of basic cardiac
      function. Although PPAR-alpha and PPAR-gamma synthetic agonists, hypolipidemic
      and antidiabetic drugs, have been reported to protect the heart against
      ischemia/reperfusion injury, it is still a matter of debate whether PPAR
      activation plays a beneficial or detrimental role in myocardial response to
      ischemia, in particular, in pathological conditions. This article reviews some
      findings demonstrating the impact of PPAR activation on cardiac resistance to
      ischemia in normal and pathologically altered heart. Specifically, it addresses
      the issue of susceptibility to ischemia in the diabetic myocardium, with
      particular regards to the role of PPAR. Finally, involvement of PPAR in the
      mechanisms of lipid-independent cardioprotective effects of some hypolipidemic
      drugs is also discussed.

PMID- 22131315
TI  - Substituted derivatives of indole acetic acid as aldose reductase inhibitors with
      antioxidant activity: structure-activity relationship.
AB  - Although multiple biochemical pathways are likely to be responsible for the
      pathogenesis of diabetic complications, substantial evidence suggests a key role
      for the polyol pathway and oxidative stress initiated by hyperglycemia. Thus
      aldose reductase, the first enzyme of the polyol pathway, has been identified as
      a potential target of pharmacological intervention to prevent diabetic
      complications. Aldose reductase inhibitors endowed with antioxidant activity
      would be dually beneficial. The aim of the study was to evaluate the structure
      activity relationship of commercially available indole derivatives supported by
      the molecular modeling of their interaction with the enzyme aldose reductase from
      the viewpoint of the inhibitory effect on the enzyme and their antioxidant
      activity. The partially purified aldose reductase was prepared from rabbit eye
      lenses. In vitro inhibiton of the aldose reductase was determined by a
      conventional method. Antioxidant action of the compounds was documented in a DPPH
      test. Marked differences were recorded in the aldose reductase inhibition
      activities of 1- and 3-indole acetic acid derivatives. The interaction energies
      of the inhibitor vs. enzyme-NADP(+) complexes, calculated by computer aided
      molecular modeling, were in agreement with the higher inhibitory efficacy of 1
      indole acetic acid in contrast with 3-indole acetic acid. The more efficient 1
      indole acetic acid was proved to create stronger electrostatic interaction with
      NADP(+). However, the order of the antioxidant activities of the compounds
      studied was not in agreement with that of the inhibitory efficacies.

PMID- 22131316
TI  - Nicotine reduces mortality of developing rats exposed to high-altitude hypoxia
      and partially suppresses the duration of cortical epileptic afterdischarges.
AB  - Nicotine has been repeatedly reported as substance possessing neuroprotective
      properties. This study focused on the possible beneficial effects of nicotine
      against the high-altitude hypoxia (9000 m for one hour). 15 min prior to hypoxia
      exposition rats (12- and 35-day-old) were treated with nicotine. Next day
      electrodes have been implanted and the effects of nicotine and hypoxia (or both
      factors) on duration of afterdischarges (ADs) were tested. Administration of
      nicotine declined the hypoxia-induced mortality in 35-day-old animals. Nicotine
      pretreatment had no effect on ADs duration in 12-day-old pups, therefore brought
      about suppression of ADs in 35-day-old animals. Taken together, our data show
      that nicotine exhibits an anticonvulsant effect that is age-dependent. The
      mechanisms of nicotine neuroprotective properties include probably the influence
      of calcium homeostasis, increase synthesis of variety of growth factors,
      inhibition of the caspase cascades and antioxidant capability of nicotine.

PMID- 22131317
TI  - Evaluation of trace elements and oxidative stress levels in the liver and kidney
      of streptozotocin-induced experimental diabetic rat model.
AB  - In this study, we aimed to investigate the relationship among trace elements (Cu,
      Fe, Zn and Mg) on oxidative and anti-oxidative substances in liver and kidneys
      tissues in streptozotocin (STZ) diabetic rat model. The mean levels of Fe and Cu
      were found significantly higher in the liver and kidneys of the diabetic rats, in
      comparison to the control rats. On the other hand, the mean levels of Zn and Mg
      in the liver and kidneys of the diabetic rats were significantly lower than in
      the control rats. The liver and kidneys malonaldehyde (MDA) levels of the
      experimental group were found to be higher than in the control group (p < 0.001;
      p < 0.01, respectively) after 4 weeks of the experimental period. Superoxide
      dismutase (SOD) activities and glutathione (GSH) levels in the liver tissue of
      STZ-induced diabetic rats were found to be lower in the experimental group than
      in the control group (p < 0.01). SOD activity and GSH concentration in kidneys of
      the diabetic rats were significantly diminished with respect to the control group
      (p < 0.01). In conclusion, the present results indicate that the increase of Fe
      and Cu together with decreas of Zn and Mg concentration in liver and kidney of
      STZ-induced diabetic rats may be involved in disturbances of oxidative balance in
      both the tissues. Therefore, these findings may contribute to explain the role of
      impaired ion metabolism of some elements in the progression of diabetic oxidative
      complications.

PMID- 22131318
TI  - Age-dependent ultrastructural changes of coronary artery in spontaneously
      hypertensive rats.
AB  - The age-dependent differences in basic cardiovascular parameters, geometry and
      structure of coronary arteries between Wistar and spontaneously hypertensive rats
      (SHR) were evaluated. SHR of the age 3-, 9-, 17-, and 52-week and age-matched
      Wistar rats were used. Blood pressure (BP) was measured by the plethysmographic
      method. Animals were perfused with a glutaraldehyde fixative under pressure of 90
      mmHg (3-week-old) and 120 mmHg (9-, 17-, 52-week-old). Coronary arteries were
      processed for electron microscopy. The proportions and cross sectional areas
      (CSA) of extracellular matrix in intima and media, endothelial and muscle cells
      were determined by point counting method. Cardiac hypertrophy and except of 3
      week-old rats also BP increase and coronary wall hypertrophy was found in all
      ontogenic periods in SHR compared to Wistar rats. Arterial wall hypertrophy was
      evoked by increase of CSA of medial extracellular matrix and smooth muscle cells.
      In 52-week-old SHR, CSA of muscle cells did not differ from that in 17-week-old
      SHR but the CSA of intimal and medial extracellular matrix significantly
      increased. The CSA of endothelial cells and CSA of intimal extracellular matrix
      were increased only in 52-week-old SHR. The independency between BP and
      trophicity of individual components of the coronary wall during ontogeny of SHR
      was documented.

PMID- 22131319
TI  - Study of the effect of DNA polymorphisms in the mannose-binding lectin gene
      (MBL2) on disease severity in Slovak cystic fibrosis patients.
AB  - Lung infections are the leading cause of morbidity and mortality in cystic
      fibrosis (CF). Mannose-binding lectin (MBL) is a key factor in innate immunity.
      We therefore investigated whether MBL2 gene variants are associated with
      pulmonary function or susceptibility to Pseudomonas aeruginosa and Burkholderia
      cepacia infection in Slovak patients affected with CF. DNA polymorphisms in exon
      1 and the promoter region were typed by single base primer extension assay in 91
      patients and 100 healthy controls. The concentrations of MBL protein were
      determined in 34 patients by a sandwich enzyme-linked immunosorbent assay, and
      spirometric and microbiological data were collected from medical records. In this
      study we found that MBL2 genotypes were associated neither with earlier
      acquisition of P. aeruginosa or B. cepacia nor with reduced pulmonary function
      among patients. Although MBL2 genotypes were associated with the MBL2 protein
      serum level, results were statistically significant only for polymorphisms in
      exon 1, with p = 0.0008. The role of the MBL2 gene in lung disease severity in CF
      patients represents a very complex phenomenon where both genetic and
      environmental factors play an important role in addition to that of the MBL2
      gene. Understanding this complexity requires further studies based on a broader
      scale of genetic factors involving both a whole-genome approach and a larger
      patient cohort.

PMID- 22131320
TI  - Mutation analysis of PMP22 in Slovak patients with Charcot-Marie-Tooth disease
      and hereditary neuropathy with liability to pressure palsies.
AB  - Charcot-Marie-Tooth disease (CMT) and related peripheral neuropathies are the
      most commonly inherited neurological disorders in humans, characterized by
      clinical and genetic heterogeneity. The most prevalent clinical entities
      belonging to this group of disorders are CMT type 1A (CMT1A) and hereditary
      neuropathy with liability to pressure palsies (HNPP). CMT1A and HNPP are
      predominantly caused by a 1.5 Mb duplication and deletion in the chromosomal
      region 17p11.2, respectively, and less frequently by other mutations in the
      peripheral myelin protein 22 (PMP22) gene. Despite being relatively common
      diseases, they haven't been previously studied in the Slovak population.
      Therefore, the aim of this study was to identify the spectrum and frequency of
      PMP22 mutations in the Slovak population by screening 119 families with CMT and 2
      families with HNPP for causative mutations in this gene. The copy number
      determination of PMP22 resulted in the detection of CMT1A duplication in 40
      families and the detection of HNPP deletion in 7 families, 6 of which were
      originally diagnosed as CMT. Consequent mutation screening of families without
      duplication or deletion using dHPLC and sequencing identified 6 single base
      changes (3 unpublished to date), from which only c.327C>A (Cys109X) present in
      one family was provably causative. These results confirm the leading role of
      PMP22 mutation analysis in the differential diagnosis of CMT and show that the
      spectrum and frequency of PMP22 mutations in the Slovak population is comparable
      to that seen in the global population.

PMID- 22131321
TI  - The effects of chronic long-term intermittent hypobaric hypoxia on blood rheology
      parameters.
AB  - The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on blood
      rheology is not completely investigated. We designed this study to determine the
      effect of CLTIHH on blood rheology parameters. Present study was performed in 16
      male Spraque-Dawley rats that divided into CLTIHH and Control groups. To obtain
      CLTIHH, rats were placed in a hypobaric chamber (430 mmHg; 5 hours/day, 5
      days/week, 5 weeks). The control rats stayed in the same environment as the
      CLTIHH rats but they breathed room air. In the blood samples aspirated from the
      heart, hematocrit, whole blood viscosity, plasma viscosity, plasma fibrinogen
      concentration, erythrocyte rigidity index and oxygen delivery index were
      determined. The whole blood viscosity, plasma viscosity, hematocrit and
      fibrinogen concentration values in the CLTIHH group were found to be higher than
      those of the control group. However, no significant difference was found in
      erythrocyte rigidity index and oxygen delivery index between the groups. Our
      results suggested that CLTIHH elevated whole blood viscosity by increasing plasma
      viscosity, fibrinogen concentration and hematocrit value without effecting the
      erythrocyte deformability. Hence, CLTIHH that may occur in intermittent high
      altitude exposure and some severe obstructive sleep apnea (OSA) patients may be
      responsible for hemorheologic changes in those subjects.

PMID- 22131322
TI  - The aqueous garlic, onion and leek extracts release nitric oxide from S
      nitrosoglutathione and prolong relaxation of aortic rings.
AB  - Garlic, onion and leek have beneficial effects in treatment of numerous health
      disorders. The aim of the present study was to investigate underlying molecular
      mechanisms. To test the potency of the aqueous garlic, onion and leek extracts to
      release NO from GSNO we have measured NO oxidation product, NO(2)-, by the Griess
      reagent method. Further, we studied the ability of garlic extract to relax
      noradrenaline-precontracted rat aortic rings in the presence of GSNO and effects
      of garlic extract on electrical properties of rat heart intracellular chloride
      channels. We have observed that: i) garlic, onion and leek extracts released NO
      from GSNO in the order: garlic > onion > leek; ii) the ability of garlic extract
      to release NO was pH-dependent (8.0 > 7.4 > 6.0) and potentiated by thiols (Cys
      >> GSH = N-acetyl-cysteine > oxidized glutathione) at concentration 100 umol/l;
      iii) the garlic extract (0.045 mg/ml) prolonged relaxation time of aortic rings
      induced by GSNO (50 nmol/l) and inhibited intracellular chloride channels. We
      suggest that NO-releasing properties of the garlic, onion and leek extracts and
      their interaction with Cys and GSH are involved in NO-signalling pathway which
      contributes to some of its numerous beneficial biological effects.

PMID- 22131323
TI  - T-type calcium channel blockers - new and notable.
AB  - Since cloning of the T-type or Ca(V)3.n calcium channel family in 1998-1999 much
      progress was made in investigation of their regulation. Most effective metal
      Ca(V)3 channel blockers are trivalent cations from lanthanide group together with
      transition metals La(3+) and Y(3+). Divalent cations Zn(2+), Cu(2+) and Ni(2+)
      inhibit Ca(V)3.2 channels more efficiently than Ca(V)3.1 and Ca(V)3.3 channels
      via second high-affinity binding site including histidine H191 specific for the
      Ca(V)3.2 channel. Dihydropyridines and phenylalkylamines in addition to block of
      L-type calcium channel can inhibit Ca(V)3 channels in clinically relevant
      concentration.

PMID- 22131324
TI  - Investigation of a weak magnetic field effect on the in vitro catalytic activity
      of adenosine deaminase and xanthine oxidase.
AB  - The effect of a weak magnetic field (MF) on adenosine deaminase (ADA) and
      xanthine oxidase (XOD) activities have been investigated. A 50 Hz uniform MF was
      generated, and the magnitude of the field was kept constant at 5.8 mT. The
      changes in ADA activity over time were significantly different in and out of the
      MF; MF caused a steeper decline in ADA activity compared to the situation when no
      MF is present. In addition, MF caused a significant increase in XOD activity.
      There were no significant time-related changes for either enzyme in the absence
      of the MF. We suggest that a weak MF affects enzymatic systems.

PMID- 22131325
TI  - Extremely low frequency magnetic field induces oxidative stress in mouse
      cerebellum.
AB  - We have investigated whether extremely low frequency magnetic field (ELF-MF)
      induces lipid peroxidation and reactive oxygen species in mouse cerebellum. After
      exposure to 60 Hz ELF-MF at 2.3 mT intensity for 3 hours, there was a significant
      increase in malondialdehyde level and hydroxyl radical. ELF-MF significantly
      induced concomitant increase in superoxide dismutase without alteration in
      glutathione peroxidase activity. While glutathione contents were not altered,
      ascorbic acid levels were significantly decreased by ELF-MF exposure. These
      results indicate that ELF-MF may induce oxidative stress in mouse cerebellum.
      However, the mechanism remains further to be characterized.

PMID- 22131326
TI  - Obtaining maximum exsanguination of the hand, preserving sterility, and avoiding
      trauma to the digits: a simple technique.

PMID- 22131327
TI  - Protection from secondary dengue virus infection in a mouse model reveals the
      role of serotype cross-reactive B and T cells.
AB  - The four dengue virus (DENV) serotypes cause dengue fever and dengue hemorrhagic
      fever/dengue shock syndrome. Although severe disease has been associated with
      heterotypic secondary DENV infection, most secondary DENV infections are
      asymptomatic or result in classic DF. The role of cross-reactive immunity in
      mediating cross-protection against secondary heterotypic DENV infection is not
      well understood. DENV infection of IFN-alpha/beta and IFN-gamma receptor
      deficient (AG129) mice reproduces key features of human disease. We previously
      demonstrated a role in cross-protection for pre-existing cross-reactive Abs,
      maintained by long-lived plasma cells. In this study, we use a sequential
      infection model, infecting AG129 mice with DENV-1, followed by DENV-2 6-8 wk
      later. We find that increased DENV-specific avidity during acute secondary
      heterotypic infection is mediated by cross-reactive memory B cells, as evidenced
      by increased numbers of DENV-1-specific cells by ELISPOT and higher avidity
      against DENV-1 of supernatants from polyclonally stimulated splenocytes isolated
      from mice experiencing secondary DENV-2 infection. However, increased DENV
      specific avidity is not associated with increased DENV-specific neutralization,
      which appears to be mediated by naive B cells. Adoptive transfer of DENV-1-immune
      B and T cells into naive mice prior to secondary DENV-2 infection delayed
      mortality. Mice depleted of T cells developed signs of disease, but recovered
      after secondary DENV infection. Overall, we found that protective cross-reactive
      Abs are secreted by both long-lived plasma cells and memory B cells and that both
      cross-reactive B cells and T cells provide protection against a secondary
      heterotypic DENV infection. Understanding the protective immunity that develops
      naturally against DENV infection may help design future vaccines.

PMID- 22131329
TI  - Amelioration of collagen-induced arthritis by a novel S1P1 antagonist with
      immunomodulatory activities.
AB  - Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking through the type 1
      sphingosine 1-phosphate receptor (S1P(1)) and participates in many pathological
      conditions, including autoimmune diseases. We developed a novel S1P(1)-selective
      antagonist, TASP0277308, which is structurally unrelated to S1P. This antagonist
      competitively inhibited S1P-induced cellular responses, such as chemotaxis and
      receptor internalization. Furthermore, differing from previously reported S1P(1)
      antagonists, TASP0277308 demonstrated in vivo activities to induce lymphopenia, a
      block in T cell egress from the thymus, displacement of marginal zone B cells,
      and upregulation of CD69 expression on both T and B cells, all of which
      recapitulate phenotypes of S1P(1)-deficient lymphocytes. In a mouse collagen
      induced arthritis model, TASP0277308 significantly suppressed the development of
      arthritis, even after the onset of disease. These findings provide the first
      chemical evidence to our knowledge that S1P(1) antagonism is responsible for
      immunosuppression in the treatment of autoimmune diseases and also resolve the
      discrepancies between genetic and chemical studies on the functions of S1P(1) in
      lymphocytes.

PMID- 22131328
TI  - Eosinophils preserve parasitic nematode larvae by regulating local immunity.
AB  - Eosinophils play important roles in regulation of cellular responses under
      conditions of homeostasis or infection. Intestinal infection with the parasitic
      nematode, Trichinella spiralis, induces a pronounced eosinophilia that coincides
      with establishment of larval stages in skeletal muscle. We have shown previously
      that in mouse strains in which the eosinophil lineage is ablated, large numbers
      of T. spiralis larvae are killed by NO, implicating the eosinophil as an immune
      regulator. In this report, we show that parasite death in eosinophil-ablated mice
      correlates with reduced recruitment of IL-4(+) T cells and enhanced recruitment
      of inducible NO synthase (iNOS)-producing neutrophils to infected muscle, as well
      as increased iNOS in local F4/80(+)CD11b(+)Ly6C(+) macrophages. Actively growing
      T. spiralis larvae were susceptible to killing by NO in vitro, whereas mature
      larvae were highly resistant. Growth of larvae was impaired in eosinophil-ablated
      mice, potentially extending the period of susceptibility to the effects of NO and
      enhancing parasite clearance. Transfer of eosinophils into eosinophil-ablated
      DeltadblGATA mice restored larval growth and survival. Regulation of immunity was
      not dependent upon eosinophil peroxidase or major basic protein 1 and did not
      correlate with activity of the IDO pathway. Our results suggest that eosinophils
      support parasite growth and survival by promoting accumulation of Th2 cells and
      preventing induction of iNOS in macrophages and neutrophils. These findings begin
      to define the cellular interactions that occur at an extraintestinal site of
      nematode infection in which the eosinophil functions as a pivotal regulator of
      immunity.

PMID- 22131330
TI  - Pseudomonas aeruginosa alkaline protease blocks complement activation via the
      classical and lectin pathways.
AB  - The complement system rapidly detects and kills Gram-negative bacteria and
      supports bacterial killing by phagocytes. However, bacterial pathogens exploit
      several strategies to evade detection by the complement system. The alkaline
      protease (AprA) of Pseudomonas aeruginosa has been associated with bacterial
      virulence and is known to interfere with complement-mediated lysis of
      erythrocytes, but its exact role in bacterial complement escape is unknown. In
      this study, we analyzed how AprA interferes with complement activation and
      whether it could block complement-dependent neutrophil functions. We found that
      AprA potently blocked phagocytosis and killing of Pseudomonas by human
      neutrophils. Furthermore, AprA inhibited opsonization of bacteria with C3b and
      the formation of the chemotactic agent C5a. AprA specifically blocked C3b
      deposition via the classical and lectin pathways, whereas the alternative pathway
      was not affected. Serum degradation assays revealed that AprA degrades both human
      C1s and C2. However, repletion assays demonstrated that the mechanism of action
      for complement inhibition is cleavage of C2. In summary, we showed that P.
      aeruginosa AprA interferes with classical and lectin pathway-mediated complement
      activation via cleavage of C2.

PMID- 22131331
TI  - Direct reduction of antigen receptor expression in polyclonal B cell populations
      developing in vivo results in light chain receptor editing.
AB  - Secondary Ab V region gene segment rearrangement, termed receptor editing, is a
      major mechanism contributing to B lymphocyte self-tolerance. However, the
      parameters that determine whether a B cell undergoes editing are a current
      subject of debate. We tested the role that the level of BCR expression plays in
      the regulation of receptor editing in a polyclonal population of B cells
      differentiating in vivo. Expression of a short hairpin RNA for kappa L chain RNA
      in B cells resulted in reduction in levels of this RNA and surface BCRs.
      Strikingly, fully mature and functional B cells that developed in vivo and
      efficiently expressed the short hairpin RNA predominantly expressed BCRs
      containing lambda light chains. This shift in L chain repertoire was accompanied
      by inhibition of development, increased Rag gene expression, and increased lambda
      V gene segment-cleavage events at the immature B cell stage. These data
      demonstrated that reducing the translation of BCRs that are members of the
      natural repertoire at the immature B cell stage is sufficient to promote editing.

PMID- 22131332
TI  - A structural basis for antigen presentation by the MHC class Ib molecule, Qa-1b.
AB  - The primary function of the monomorphic MHC class Ib molecule Qa-1(b) is to
      present peptides derived from the leader sequences of other MHC class I molecules
      for recognition by the CD94-NKG2 receptors expressed by NK and T cells. Whereas
      the mode of peptide presentation by its ortholog HLA-E, and subsequent
      recognition by CD94-NKG2A, is known, the molecular basis of Qa-1(b) function is
      unclear. We have assessed the interaction between Qa-1(b) and CD94-NKG2A and
      shown that they interact with an affinity of 17 MUM. Furthermore, we have
      determined the structure of Qa-1(b) bound to the leader sequence peptide, Qdm
      (AMAPRTLLL), to a resolution of 1.9 A and compared it with that of HLA-E. The
      crystal structure provided a basis for understanding the restricted peptide
      repertoire of Qa-1(b). Whereas the Qa-1(b-AMAPRTLLL) complex was similar to that
      of HLA-E, significant sequence and structural differences were observed between
      the respective Ag-binding clefts. However, the conformation of the Qdm peptide
      bound by Qa-1(b) was very similar to that of peptide bound to HLA-E. Although a
      number of conserved innate receptors can recognize heterologous ligands from
      other species, the structural differences between Qa-1(b) and HLA-E manifested in
      CD94-NKG2A ligand recognition being species specific despite similarities in
      peptide sequence and conformation. Collectively, our data illustrate the
      structural homology between Qa-1(b) and HLA-E and provide a structural basis for
      understanding peptide repertoire selection and the specificity of the interaction
      of Qa-1(b) with CD94-NKG2 receptors.

PMID- 22131333
TI  - Akt induces osteoclast differentiation through regulating the GSK3beta/NFATc1
      signaling cascade.
AB  - SHIP is an SH2-containing inositol-5-phosphatase expressed in hematopoietic
      cells. It hydrolyzes the PI3K product PI(3,4,5)P(3) and blunts the PI3K-initiated
      signaling pathway. Although the PI3K/Akt pathway has been shown to be important
      for osteoclastogenesis, the molecular events involved in osteoclast
      differentiation have not been revealed. We demonstrate that Akt induces
      osteoclast differentiation through regulating the GSK3beta/NFATc1 signaling
      cascade. Inhibition of the PI3K by LY294002 reduces formation of osteoclasts and
      attenuates the expression of NFATc1, but not that of c-Fos. Conversely,
      overexpression of Akt in bone marrow-derived macrophages (BMMs) strongly induced
      NFATc1 expression without affecting c-Fos expression, suggesting that PI3K/Akt
      mediated NFATc1 induction is independent of c-Fos during RANKL-induced
      osteoclastogenesis. In addition, we found that overexpression of Akt enhances
      formation of an inactive form of GSK3beta (phospho-GSK3beta) and nuclear
      localization of NFATc1, and that overexpression of a constitutively active form
      of GSK3beta attenuates osteoclast formation through downregulation of NFATc1.
      Furthermore, BMMs from SHIP knockout mice show the increased expression levels of
      phospho-Akt and phospho-GSK3beta, as well as the enhanced osteoclastogenesis,
      compared with wild type. However, overexpression of a constitutively active form
      of GSK3beta attenuates RANKL-induced osteoclast differentiation from SHIP
      deficient BMMs. Our data suggest that the PI3K/Akt/GSK3beta/NFATc1 signaling axis
      plays an important role in RANKL-induced osteoclastogenesis.

PMID- 22131334
TI  - IDO and regulatory T cell support are critical for cytotoxic T lymphocyte
      associated Ag-4 Ig-mediated long-term solid organ allograft survival.
AB  - Costimulatory blockade of CD28-B7 interaction with CTLA4Ig is a well-established
      strategy to induce transplantation tolerance. Although previous in vitro studies
      suggest that CTLA4Ig upregulates expression of the immunoregulatory enzyme IDO in
      dendritic cells, the relationship of CTLA4Ig and IDO in in vivo organ
      transplantation remains unclear. In this study, we studied whether concerted
      immunomodulation in vivo by CTLA4Ig depends on IDO. C57BL/6 recipients receiving
      a fully MHC-mismatched BALB/c heart graft treated with CTLA4Ig + donor-specific
      transfusion showed indefinite graft survival (>100 d) without signs of chronic
      rejection or donor specific Ab formation. Recipients with long-term surviving
      grafts had significantly higher systemic IDO activity as compared with rejectors,
      which markedly correlated with intragraft IDO and Foxp3 levels. IDO inhibition
      with 1-methyl-dl-tryptophan, either at transplant or at postoperative day 50,
      abrogated CTLA4Ig + DST-induced long-term graft survival. Importantly, IDO1
      knockout recipients experienced acute rejection and graft survival comparable to
      controls. In addition, alphaCD25 mAb-mediated depletion of regulatory T cells
      (Tregs) resulted in decreased IDO activity and again prevented CTLA4Ig + DST
      induced indefinite graft survival. Our results suggest that CTLA4Ig-induced
      tolerance to murine cardiac allografts is critically dependent on synergistic
      cross-linked interplay of IDO and Tregs. These results have important
      implications for the clinical development of this costimulatory blocker.

PMID- 22131336
TI  - Fundamental characteristics of the immunoglobulin VH repertoire of chickens in
      comparison with those of humans, mice, and camelids.
AB  - Examination of 1269 unique naive chicken V(H) sequences showed that the majority
      of positions in the framework (FW) regions were maintained as germline, with high
      mutation rates observed in the CDRs. Many FW mutations could be clearly related
      to the modulation of CDR structure or the V(H)-V(L) interface. CDRs 1 and 2 of
      the V(H) exhibited frequent mutation in solvent-exposed positions, but
      conservation of common structural residues also found in human CDRs at the same
      positions. In comparison with humans and mice, the chicken CDR3 repertoire was
      skewed toward longer sequences, was dominated by small amino acids (G/S/A/C/T),
      and had higher cysteine (chicken, 9.4%; human, 1.6%; and mouse, 0.25%) but lower
      tyrosine content (chicken, 9.2%; human, 16.8%; and mouse 26.4%). A strong
      correlation (R(2) = 0.97) was observed between increasing CDR3 length and higher
      cysteine content. This suggests that noncanonical disulfides are strongly favored
      in chickens, potentially increasing CDR stability and complexity in the topology
      of the combining site. The probable formation of disulfide bonds between CDR3 and
      CDR1, FW2, or CDR2 was also observed, as described in camelids. All features of
      the naive repertoire were fully replicated in the target-selected, phage
      displayed repertoire. The isolation of a chicken Fab with four noncanonical
      cysteines in the V(H) that exhibits 64 nM (K(D)) binding affinity for its target
      proved these constituents to be part of the humoral response, not artifacts. This
      study supports the hypothesis that disulfide bond-constrained CDR3s are a
      structural diversification strategy in the restricted germline v-gene repertoire
      of chickens.

PMID- 22131335
TI  - IL-22 is required for imiquimod-induced psoriasiform skin inflammation in mice.
AB  - Psoriasis is a common chronic autoimmune skin disease of unknown cause that
      involves dysregulated interplay between immune cells and keratinocytes. IL-22 is
      a cytokine produced by the TH1, TH17, and TH22 subsets that are functionally
      implicated in the psoriatic pathology. We assessed the role of IL-22 in a mouse
      model where psoriasiform skin inflammation is triggered by topical application of
      the TLR7/8 agonist imiquimod. At the macroscopic level, scaly skin lesions
      induced by daily applications of imiquimod in wild-type mice were almost totally
      absent in IL-22-deficient mice or in mice treated with a blocking anti-IL-22 Ab.
      At the microscopic level, IL-22-deficient mice showed a dramatic decrease in the
      development of pustules and a partial decrease in acanthosis. At the molecular
      level, the absence or inhibition of IL-22 strongly decreased the expression of
      chemotactic factors such as CCL3 and CXCL3 and of biomarkers such as S100A8,
      S100A7, and keratin 14, which reflect the antimicrobial and hyperproliferative
      responses of keratinocytes. IL-22 also played a major role in neutrophil
      infiltration after imiquimod treatment. IL-23 was required for IL-22 production,
      and gammadelta TCR lymphocytes represented the major source of IL-22 in lymph
      nodes from imiquimod-treated mice. However, T cells were not absolutely required
      for IL-22 production because imiquimod-induced IL-22 expression in the skin is
      still preserved in Rag2(-/-) mice. Taken together, our data show that IL-22 is
      required for psoriasis-like lesions in the mouse imiquimod model and is produced
      by both T cells and innate immune cells.

PMID- 22131337
TI  - UXT-V1 facilitates the formation of MAVS antiviral signalosome on mitochondria.
AB  - Virus infection induces the MAVS-TNFR-associated factor (TRAF) 3 signaling axis
      on mitochondria. It remains to elucidate the corresponding regulatory processes.
      In this study, we identify UXT-V1 as a novel TRAF3-binding protein. UXT-V1 is
      critical for the virus-induced activation of NF-kappaB and IFN regulatory factor
      3. Reduction of UXT-V1 impairs the induction of IFN-beta and attenuates the host
      antiviral responses. The N-terminal TRAF-binding motif of UXT-V1 binds to the C
      terminal TRAF domain of TRAF3, thus facilitating the interaction between TRAF3
      and MAVS. Notably, TRAF3 and TNFR-associated death domain protein are recruited
      onto mitochondria upon virus infection. These translocations are blocked when
      knocking down UXT-V1. Thus, UXT-V1 represents a novel integral component of the
      MAVS signalosome on mitochondria, mediating the innate antiviral signal
      transduction.

PMID- 22131338
TI  - Use of a human influenza challenge model to assess person-to-person transmission:
      proof-of-concept study.
AB  - BACKGROUND: Influenza transmission in humans remains poorly understood. In
      particular, the relative contribution of contact, large droplet, and aerosol
      transmission is unknown. The aims of this proof-of-concept study were to
      determine whether an experimentally induced influenza infection is transmissible
      between humans and whether this would form a viable platform for future studies.
      METHODS: In a quarantine facility, healthy volunteers ("donors") were inoculated
      with A/Wisconsin/67/2005 (H3N2) influenza virus via intranasal drops. On study
      days 2 and 3 "recipient" volunteers were exposed to donors under close living
      conditions. Volunteers socialized for 30 hours during a 2-day period. Infection
      was confirmed by >=1 positive results from polymerase chain reaction, virus
      culture, or serology. RESULTS: After inoculation, 4 of 9 donors developed
      symptoms consistent an influenza-like illness (ILI) and 7 of 9 were proven to be
      influenza-infected. After exposure, 4 of 15 recipients developed symptoms of ILI
      and 3 of 15 were proven to be infected. Serum collected within 2 days of study
      initiation indicated that 1 donor and 3 recipients were seropositive at study
      initiation. After adjustment for preexposure immunity, the overall secondary
      attack rate was 25% (3 of 12). CONCLUSIONS: Experimental human exposure studies
      offer an attractive potential method for answering outstanding questions related
      to influenza transmission and the evaluation of interventions to reduce it.

PMID- 22131339
TI  - Patterns of practice in intensity-modulated radiation therapy and image-guided
      radiation therapy for prostate cancer in Japan.
AB  - BACKGROUND: The purpose of this study was to compare the prevalence of treatment
      techniques including intensity-modulated radiation therapy and image-guided
      radiation therapy in external-beam radiation therapy for prostate cancer in
      Japan. METHODS: A national survey on the current status of external-beam
      radiation therapy for prostate cancer was performed in 2010. We sent
      questionnaires to 139 major radiotherapy facilities in Japan, of which 115
      (82.7%) were returned. RESULTS: Intensity-modulated radiation therapy was
      conducted at 67 facilities (58.3%), while image-guided radiation therapy was
      conducted at 70 facilities (60.9%). Simulations and treatments were performed in
      the supine position at most facilities. In two-thirds of the facilities, a
      filling bladder was requested. Approximately 80% of the facilities inserted a
      tube or encouraged defecation when the rectum was dilated. Some kind of fixation
      method was used at 102 facilities (88.7%). Magnetic resonance imaging was
      routinely performed for treatment planning at 32 facilities (27.8%). The median
      total dose was 76 Gy with intensity-modulated radiation therapy and 70 Gy with
      three-dimensional radiation therapy. The doses were prescribed at the isocenter
      at the facilities that conducted three-dimensional radiation therapy. In
      contrast, the dose prescription varied at the facilities that conducted intensity
      modulated radiation therapy. Of the 70 facilities that could perform image-guided
      radiation therapy, 33 (47.1%) conducted bone matching, 28 (40.0%) conducted
      prostate matching and 9 (12.9%) used metal markers. Prostate or metal marker
      matching tended to produce a smaller margin than bone matching. CONCLUSIONS: The
      results of the survey identified current patterns in the treatment planning and
      delivery processes of external-beam radiation therapy for prostate cancer in
      Japan.

PMID- 22131340
TI  - Cigarette smoking and esophageal cancer risk: an evaluation based on a systematic
      review of epidemiologic evidence among the Japanese population.
AB  - OBJECTIVE: Although cigarette smoking is considered as an important risk factor
      for esophageal cancer, the magnitude of the association might be varied among
      geographic areas. Therefore, we reviewed epidemiologic studies on the association
      between cigarette smoking and esophageal cancer among the Japanese population.
      METHODS: Original articles were obtained from MEDLINE searched using PubMed or
      from searches of the Ichushi database, complemented by manual searches.
      Evaluation of associations was based on the strength of evidence ('convincing',
      'probable', 'possible' or 'insufficient') and the magnitude of association
      ('strong', 'moderate', 'weak' or 'no association'), together with biological
      plausibility as previously evaluated by the International Agency for Research on
      Cancer. RESULTS: We identified four cohort studies and 11 case-control studies.
      All cohort studies and eight case-control studies showed strong positive
      associations between esophageal cancer and cigarette smoking. All cohort studies
      and five case-control studies showed that cigarette smoking had dose-response
      relationships with esophageal cancer. Meta-analysis of 12 studies indicated that
      the summary estimate for ever smokers relative to never smokers was 3.01 (95%
      confidence interval: 2.30-3.94). Summary relative risk for current and former
      smokers relative to never smokers was 3.73 (2.16-6.43) and 2.21 (1.60-3.06),
      respectively. CONCLUSIONS: We conclude that there is convincing evidence that
      cigarette smoking strongly increases the risk of esophageal cancer in the
      Japanese population.

PMID- 22131341
TI  - Interferon-alpha-based immunotherapy in metastatic renal cell carcinoma patients
      with the primary tumor in situ.
AB  - OBJECTIVE: We reviewed the outcomes of metastatic renal cell carcinoma patients
      with the primary tumor in situ who initially underwent interferon-alpha-based
      immunotherapy to evaluate the effect of this therapy on metastatic sites as well
      as primary kidney tumor and survival. METHODS: Thirty-one patients, for whom
      upfront cytoreductive nephrectomy was considered to be inappropriate because of
      poor performance status and far-advanced disease, were the subject of the present
      study. Tumor response and reduction in the size of metastatic sites and primary
      kidney tumor were assessed. Overall survival distributions were estimated using
      the Kaplan-Meier method with the significance determined using the log-rank test.
      RESULTS: Partial response was observed in 11 patients, yielding an overall
      response rate of 35%. Seventeen patients had regression or stabilization of
      metastatic sites, while progression of metastatic sites was observed in the
      remaining 14 patients. Regarding the maximum response of primary kidney tumor, a
      reduction in kidney primary tumor size was observed in 42% of the patients and
      the mean reduction rate in these patients was 18.2% (range: 3-36%). Furthermore,
      the reduction in the size of metastatic sites was significantly associated with
      that in the size of primary kidney tumor (R(2)= 0.432, P< 0.0001). The median
      survival for the 31 patients was 17 months. The median survival was 42 months in
      patients with regression or stabilization of metastatic sites and 7 months in
      those without (P< 0.001). CONCLUSIONS: The present study suggests that metastatic
      sites as well as primary kidney tumor respond to interferon-alpha-based
      immunotherapy in metastatic renal cell carcinoma patients with primary tumor in
      situ.

PMID- 22131342
TI  - Availability of psychiatric consultation-liaison services as an integral
      component of palliative care programs at Japanese cancer hospitals.
AB  - OBJECTIVE: Collaboration between psychiatry and palliative medicine has the
      potential to enhance the quality of medical practice. The integration between
      palliative care and psychiatry has been attempted only in discrete medical
      settings and is not yet firmly established as an institution. Our objective was
      to determine the availability and degree of integration between psychiatric
      consultation-liaison services and palliative care in Japan. METHODS: A survey
      questionnaire was mailed to consultation-liaison psychiatrists at 375 government
      designated cancer hospitals regarding their consultation-liaison services.
      RESULTS: A total of 375 survey questionnaires were sent to consultation-liaison
      psychiatrists, with a response rate of 64.8%. Designated cancer hospitals with
      approved palliative care teams were significantly more likely to have a
      consultation-liaison psychiatrist in the palliative care team than those in non
      approved palliative care teams [80/80 (100%) versus 110/153 (73%); P= 0.008].
      Approved palliative care teams had double the number of referrals, conducted
      rounds more frequently and held conferences more frequently. Psychiatrists of the
      approved palliative care teams spent more of their time on palliative care
      consultations, adhered more closely to consultation processes and contributed
      more actively to the integration of developmental perspectives in treatment
      plans. CONCLUSIONS: In Japan, most designated cancer hospitals with approved
      palliative care teams were more likely to integrate psychiatric consultation
      liaison services into their palliative care programs. Systematic strategies for
      integration between palliative care and consultation-liaison psychiatry would
      contribute to the provision of appropriate psychosocial care for cancer patients
      and families at all stages.

PMID- 22131343
TI  - Stimulation of Ly-6G on neutrophils in LPS-primed mice induces platelet
      activating factor (PAF)-mediated anaphylaxis-like shock.
AB  - Previously, two anti-Ly-6G mAb-RB6-8C5 and 1A8-have been used to deplete
      neutrophils in mice and to clarify their involvement in immune responses. During
      the course of experiments on neutrophil depletion, we noticed that i.v. injection
      of RB6-8C5 or 1A8 induced anaphylaxis-like shock in mice pretreated i.v. with
      LPS. Signs of shock, such as hypothermia, appeared within a few minutes, and the
      mice died of shock within 20 min of the antibody injection. In vivo experiments,
      including depletion of various cell types, indicated that neutrophils and
      macrophages (but not platelets, basophils, or mast cells) are involved in the
      shock. Experiments using various drugs and gene-targeted mice demonstrated that
      PAF is the central mediator of the shock. Optimal LPS priming required at least 1
      h, and the priming was associated with neutrophil accumulation within pulmonary
      and hepatic blood vessels. Consistently, following 1A8 injection into LPS
      pretreated mice, the mRNA for LysoPAFAT (a PAF biosynthetic enzyme) was markedly
      up-regulated in neutrophils accumulated in the lung but not in macrophages. These
      results suggest that (1) stimulation of Ly-6G on LPS-primed neutrophils induces
      PAF-mediated anaphylaxis-like shock in mice, (2) neutrophils are primed by LPS
      during and/or after their accumulation in lung and liver to rapidly induce
      LysoPAFAT, and (3) macrophages may play a pivotal role in the priming phase
      and/or in the challenge phase by unknown mechanisms. These findings may be
      related to adult respiratory distress syndrome, although the natural ligand for
      Ly-6G remains to be identified.

PMID- 22131344
TI  - Azithromycin drives in vitro GM-CSF/IL-4-induced differentiation of human blood
      monocytes toward dendritic-like cells with regulatory properties.
AB  - Azithromycin, a macrolide antibacterial, has been shown to modify the phenotype
      of macrophages. We have investigated whether azithromycin in vitro is able to
      modulate the differentiation of human blood monocytes to DCs. iA-DCs appear to
      have a unique phenotype, characterized by increased granularity, adherence, and a
      surface molecule expression profile similar to that of MDCs, namely, CD1a-CD14
      CD71+CD209(high), as well as high CD86 and HLA-DR expression. The iA-DC phenotype
      is associated with increased IL-6 and IL-10 release, increased CCL2 and CCL18
      expression and release, and M-CSF expression, as well as reduced CCL17 expression
      and release. Upon maturation with LPS, A-DCs and MDCs exhibit decreased
      expression of HLA-DR and costimulatory molecules, CD40 and CD83, as well as an
      increase in IL-10 and a decrease in CCL17 and CXCL11 secretion. These modulated
      responses of iA-DCs were associated with the ability to reduce a MLR, together
      with enhanced phagocytic and efferocytotic properties. Azithromycin, added 2 h
      before activation of iDCs with LPS, enhanced IL-10 release and inhibited IL-6, IL
      12p40, CXCL10, CXCL11, and CCL22 release. In conclusion, azithromycin modulates
      the differentiation of blood monocyte-derived DCs to form iA-DCs with a distinct
      phenotype similar to that of iMDCs, accompanied by enhanced phagocytic and
      efferocytic capabilities. It also modifies LPS-induced DC maturation by
      decreasing surface molecule expression required for T cell activation, increasing
      IL-10 production, and inducing MLR-reducing properties.

PMID- 22131345
TI  - Myeloperoxidase associated with neutrophil extracellular traps is active and
      mediates bacterial killing in the presence of hydrogen peroxide.
AB  - A variety of inflammatory stimuli induces NETs. These structures consist of a
      network of chromatin strands associated with predominately granule proteins,
      including MPO. NETs exhibit antimicrobial activity, which is proposed to augment
      the more-established mechanism of phagosomal killing. They may also be
      detrimental to the host in situations such as chronic inflammation or severe
      sepsis. The objective of this study was to establish whether MPO associated with
      NETs is active and able to kill bacteria. Neutrophils were stimulated with PMA to
      release NETs. Peroxidase activity measurements were performed and showed that
      enzymatically active MPO was released from the neutrophils, 2-4 h after
      stimulation, concomitant with NET formation. Approximately 30% of the total
      cellular MPO was released, with the majority bound to the NETs. The bound enzyme
      retained its activity. Staphylococcus aureus were not killed when added to
      preformed NETs under our assay conditions. However, addition of H(2)O(2) to the
      bacteria in the presence of NETs resulted in MPO-dependent killing, which was
      observed with NETs in situ and with NETs when they were removed from the
      neutrophils by limited DNase digestion. Our results show that the enzymatic
      activity of MPO on NETs could contribute to antimicrobial activity or tissue
      injury when NETs are released from neutrophils at sites of infection or
      inflammation.

PMID- 22131346
TI  - Mechanisms of sex disparities in influenza pathogenesis.
AB  - Epidemiological evidence from influenza outbreaks and pandemics reveals that
      morbidity and mortality are often higher for women than men. Sex differences in
      the outcome of influenza are age-dependent, often being most pronounced among
      adults of reproductive ages (18-49 years of age) and sometimes reflecting the
      unique state of pregnancy in females, which is a risk factor for severe disease.
      Small animal models of influenza virus infection illustrate that inflammatory
      immune responses also differ between the sexes and impact the outcome of
      infection, with females generating higher proinflammatory cytokine and chemokine
      responses and experiencing greater morbidity and mortality than males. Males and
      females also respond differently to influenza vaccines, with women initiating
      higher humoral immune responses but experiencing more adverse reactions to
      seasonal influenza vaccines than men. Small animal models further show that
      elevated immunity following vaccination in females leads to greater cross
      protection against novel influenza viruses in females compared with males. Sex
      steroid hormones, including estradiol and testosterone, as well as genetic
      differences between the sexes may play roles in modulating sex differences in
      immune responses to influenza virus infection and vaccination. Future studies
      must elucidate the pathways and cellular responses that differ between the sexes
      and determine how best to use this knowledge to inform public health policy
      makers about prophylaxis and therapeutic treatments of influenza virus infections
      to ensure adequate protection in both males and females.

PMID- 22131348
TI  - Resistance to BRAF inhibitors: unraveling mechanisms and future treatment
      options.
AB  - The mitogen-activated protein kinase (MAPK) pathway has emerged as a central
      target for melanoma therapy due to its persistent activation in the majority of
      tumors. Several BRAF inhibitors aimed at curbing MAPK pathway activity are
      currently in advanced stages of clinical investigation. However, their
      therapeutic success is limited by the emergence of drug resistance, as responses
      are transient and tumors eventually recur. To develop effective and long-lasting
      therapies for melanoma patients, it is essential to understand the mechanisms
      underlying resistance to BRAF inhibitors. Here, we briefly review recent
      preclinical studies that have provided insight into the molecular mechanisms of
      resistance to BRAF inhibitors and discuss potential strategies to treat drug
      resistant melanomas.

PMID- 22131350
TI  - The principal urinary metabolite of allyl isothiocyanate, N-acetyl-S-(N
      allylthiocarbamoyl)cysteine, inhibits the growth and muscle invasion of bladder
      cancer.
AB  - Naturally occurring allyl isothiocyanate (AITC) was recently shown to be
      selectively delivered to bladder cancer tissue via urinary excretion and to
      inhibit bladder cancer growth and muscle invasion in an animal model. AITC is
      excreted in urine mainly as N-acetyl-S-(N-allylthiocarbamoyl)cysteine, more
      commonly known as the N-acetylcysteine conjugate (NAC-AITC). We show here that
      treatment of human bladder cancer UM-UC-3 cells or rat bladder cancer AY-27 cells
      with NAC-AITC at 15 MUM results in significant inhibition of cell growth and
      proliferation, together with cell cycle arrest and apoptosis. We also show that
      NAC-AITC administered orally at 10 MUmol/kg body wt inhibits cancer growth by 40%
      and muscle invasion by 49% in an orthotopic rat bladder cancer model.
      Furthermore, the anticancer activity of NAC-AITC is associated with the
      modulation of several important molecular targets, including downregulation of
      both alpha-tubulin and beta-tubulin, activation of caspase-3 and downregulation
      of vascular endothelial growth factor. These results are similar to those shown
      previously for AITC and are consistent with the understanding that NAC-AITC is a
      carrier of AITC. Furthermore, comparison of the pharmacokinetic and physical
      properties of NAC-AITC with those of AITC suggests that NAC-AITC is superior to
      AITC for potential use for prevention and therapy of bladder cancer.

PMID- 22131351
TI  - Mutations of ventricular essential myosin light chain disturb myosin binding and
      sarcomeric sorting.
AB  - AIMS: We tested the hypothesis that mutations in the human ventricular essential
      myosin light chain (hVLC-1) that are associated with hypertrophic cardiomyopathy
      (HCM) affect protein structure, binding to the IQ1 motif of cardiac myosin heavy
      chain (MYH) and sarcomeric sorting in neonatal cardiomyocytes. METHODS AND
      RESULTS: We employed circular dichroism and surface plasmon resonance
      spectroscopy to investigate structural properties and protein-protein
      interactions of a recombinant head-rod fragment of rat cardiac beta-MYH (amino
      acids 664-915) with alanine-mutated IQ2 domain (rbeta-MYH(664-915)IQ2(ala4)) and
      normal or five mutated (M149V, E143K, A57G, E56G, R154H) hVLC-1 forms. Double
      epitope-tagging competition was used to monitor the intracellular localization of
      exogenously introduced normal and E56G-mutated (hVLC-1(E56G)) hVLC-1 constructs
      in neonatal rat cardiomyocytes. Fluorescence lifetime imaging microscopy was
      applied to map the microenvironment of normal and E56G-mutated hVLC-1 in
      permeabilized muscle fibres. Affinity of M149V, E143K, A57G, and R154H mutated
      hVLC-1/rbeta-MYH(664-915)IQ2(ala4) complexes was significantly lower compared
      with the normal hVLC-1/rbeta-MYH(664-915)IQ2(ala4) complex interaction. In
      particular, the E56G mutation induced an ~30-fold lower MYH affinity. Sorting
      specificity of E56G-mutated hVLC-1 was negligible compared with normal hVLC-1.
      Fluorescence lifetime of fibres replaced with hVLC-1(E56G) increased
      significantly compared with hVLC-1-replaced fibres. CONCLUSION: Disturbed myosin
      binding of mutated hVLC-1 may provide a pathomechanism for the development of
      HCM.

PMID- 22131352
TI  - Knockdown of natriuretic peptide receptor-A enhances receptor C expression and
      signalling in vascular smooth muscle cells.
AB  - AIMS: Natriuretic peptide receptor-A (NPR-A) knockout mice exhibited an increased
      blood pressure that may also be attributed to the up-regulation of NPR-C and
      associated signalling; however, the interaction between the two receptors has not
      been investigated. In the present study, we investigated the effect of knockdown
      of NPR-A using NPR-A antisense (AS) on the expression of NPR-C and adenylyl
      cyclase (AC) signalling in A10 vascular smooth muscle cells (VSMC). METHODS AND
      RESULTS: The receptor and G protein expression was determined by western
      blotting, and AC activity was determined by measuring [(32)P]cAMP formation from
      [alpha-(32)P]ATP. Treatment of A10 VSMC with NPR-A AS decreased NPR-A and
      enhanced NPR-C expression without altering the levels of angiotensin II AT1 and
      muscarinic M2 receptors. In addition, siRNA-NPR-A also resulted in the up
      regulation of NPR-C. The re-expression of NPR-A in AS-treated cells reversed the
      enhanced expression of NPR-C to control levels. In addition, NPR-C-, AT1, and M2
      receptor-mediated inhibition of AC and Gialpha protein expression was enhanced in
      AS-treated cells, whereas NPR-A-mediated cyclic GMP (cGMP) formation and Gsalpha
      mediated stimulation of AC were significantly reduced. Pertussis toxin treatment
      attenuated the AS-induced enhanced inhibition of AC to control levels.
      Furthermore, the enhanced levels of NPR-C and Gialpha proteins were reversed to
      control levels by 8-bromo-cGMP (8Br-cGMP) and PD98059, an MEK inhibitor. In
      addition, 8Br-cGMP also attenuated AS-induced enhanced ERK1/2 phosphorylation to
      control levels. CONCLUSION: These results demonstrate that knockdown of NPR-A up
      regulates the expression of NPR-C, Gialpha proteins, and NPR-C-linked AC
      signalling and suggests a cross-talk between NPR-A and NPR-C.

PMID- 22131353
TI  - Myocardial protection with mild hypothermia.
AB  - Mild hypothermia, 32-35 degrees  C, is very potent at reducing myocardial infarct
      size in rabbits, dogs, sheep, pigs, and rats. The benefit is directly related to
      reduction in normothermic ischaemic time, supporting the relevance of early and
      rapid cooling. The cardioprotective effect of mild hypothermia is not limited to
      its recognized reduction of infarct size, but also results in conservation of
      post-ischaemic contractile function, prevention of no-reflow or microvascular
      obstruction, and ultimately attenuation of left ventricular remodelling. The
      mechanism of the anti-infarct effect does not appear to be related to diminished
      energy utilization and metabolic preservation, but rather to survival signalling
      that involves either the extracellular signal-regulated kinases and/or the
      Akt/phosphoinositide 3-kinase/mammalian target of rapamycin pathways. Initial
      clinical trials of hypothermia in patients with ST-segment elevation myocardial
      infarction were disappointing, probably because cooling was too slow to shorten
      normothermic ischaemic time appreciably. New approaches to more rapid cooling
      have recently been described and may soon be available for clinical use.
      Alternatively, it may be possible to pharmacologically mimic the protection
      provided by cooling soon after the onset of ischaemia with an activator of mild
      hypothermia signalling, e.g. extracellular signal-regulated kinase activator,
      that could be given by emergency medical personnel. Finally, the protection
      afforded by cooling can be added to that of pre- and post-conditioning because
      their mechanisms differ. Thus, myocardial salvage might be greatly increased by
      rapidly cooling patients as soon as possible and then giving a pharmacological
      post-conditioning agent immediately prior to reperfusion.

PMID- 22131354
TI  - Functional analysis of a novel antagonistic antibody against the short epitope of
      the alpha1A-adrenergic receptor.
AB  - AIMS: The alpha1A-adrenergic receptor (alpha1A-AR) regulates various vascular
      functions and participates in the pathogenesis of primary hypertension. However,
      highly specific and subtype-selective antagonists of alpha1A-AR have not been
      developed. METHODS AND RESULTS: Two novel antibodies against the short peptides
      CP-7, which is located in the second extracellular loop of alpha1A-AR, and CPE-8,
      which is located in the third extracellular loop of alpha1A-AR, were prepared.
      The two antibodies specifically bound to alpha1A-AR. However, neither antibody
      prevented [(3)H]-epinephrine or [(3)H]-prazosin from binding to the receptor. In
      vitro, the anti-CP-7 antibody inhibited Ca(2+)-dependent signal transduction
      processes including protein kinase C translocation and extracellular signal
      regulated kinase (ERK1/2) phosphorylation induced by phenylephrine (PHE). The
      anti-CP-7 antibody decreased the beating rates of neonatal rat cardiomyocytes
      with or without PHE stimulation and reduced the blood pressure of spontaneously
      hypertensive rats that were immunized with CP-7-keyhole limpet haemocyanin.
      CONCLUSION: The anti-CP-7 antibody specifically inhibited the activation of
      alpha1A-AR both in vitro and in vivo. No competition binding was found between
      anti-CP-7 and [(3)H]-epinephrine or [(3)H]-prazosin. An antibody that
      specifically inhibits a receptor could be useful in research on G-protein-coupled
      receptors that lack specific antagonists. The antibody against the epitope CP-7
      might have potential in a therapeutic application for treating primary
      hypertension.

PMID- 22131356
TI  - Prospective evaluation of an Australian pertussis toxin IgG and IgA enzyme
      immunoassay.
AB  - Serological diagnosis of recent pertussis infection is an important part of both
      clinical assessment and epidemiological documentation of this disease.
      Standardization of serological testing and interpretation remains challenging
      despite international efforts to improve it. Currently, determining the anti
      pertussis toxin (PT) IgG titer is recommended as the most accurate serological
      test in Europe and the United States, while Australia relies predominantly on
      measurement of Bordetella pertussis IgA antibody responses. Using B. pertussis
      PCR and the WHO clinical case definition as reference standards, the diagnostic
      utility of in-house anti-PT IgG and anti-PT IgA assays was evaluated
      prospectively in an Australian community-based cohort (n = 327). Patients
      provided up to four consecutive serum samples to document the kinetics of
      antibody response and decay. Previously validated cutoffs for positivity were
      converted to international units by using WHO-approved reference sera. At
      currently used cutoffs, both anti-PT IgG (>94 IU/ml) and anti-PT IgA (>20 IU/ml)
      assays had good specificity (80% [95% confidence interval {95% CI}, 68 to 88%]
      and 87% [95% CI, 77 to 94%]), but anti-PT IgG assay was consistently more
      sensitive than anti-PT IgA assay across a range of cutoffs (60 to 79% [95% CI, 53
      to 84%] versus 41 to 62% [95% CI, 34 to 69%]). The combination of anti-PT IgG and
      anti-PT IgA assays performed no better than anti-PT IgG assay alone. The anti-PT
      IgA response in children under 12 years of age was poor. The accuracy of serology
      was optimal between 2 and 8 weeks after symptom onset. Cutoffs of >94 IU/ml for
      anti-PT IgG and >20 IU/ml for anti-PT IgA correlated well with recent pertussis
      infection and were consistent with recent recommendations from the EU Pertstrain
      group. Anti-PT IgG assay was superior to anti-PT IgA assay as the test of choice
      for the diagnosis of pertussis from a single sample.

PMID- 22131355
TI  - Mucosal and systemic immune responses induced by recombinant Lactobacillus spp.
      expressing the hemagglutinin of the avian influenza virus H5N1.
AB  - To develop a safe, effective, and convenient vaccine for the prevention of highly
      pathogenic avian influenza (HPAI), we have successfully constructed two
      recombinant lactobacillus strains (LA4356-pH and DLD17-pH) that express the
      foreign HPAI virus protein hemagglutinin 1 (HA(1)). The mucosal and systemic
      immune responses triggered by these two recombinant lactobacilli following oral
      administration to BALB/c mice were evaluated. The results showed that both LA4356
      pH and DLD17-pH could significantly increase the specific anti-HA(1) IgA antibody
      level in the mucosa and the anti-HA(1) IgG level in serum, as well as stimulating
      the splenic lymphocyte proliferative reaction through increased expression of
      interleukin-4 (IL-4). Compared with LA4356-pH, DLD17-pH was more effective at
      inducing systemic and mucosal immune responses, with higher anti-HA(1)-specific
      IgA and IgG levels. Therefore, DLD17-pH could be a promising oral vaccine
      candidate against HPAI.

PMID- 22131357
TI  - Pulmonary capillary wedge pressure augments right ventricular pulsatile loading.
AB  - BACKGROUND: Right ventricular failure from increased pulmonary vascular loading
      is a major cause of morbidity and mortality, yet its modulation by disease
      remains poorly understood. We tested the hypotheses that, unlike the systemic
      circulation, pulmonary vascular resistance (R(PA)) and compliance (C(PA)) are
      consistently and inversely related regardless of age, pulmonary hypertension, or
      interstitial fibrosis and that this relation may be changed by elevated pulmonary
      capillary wedge pressure, augmenting right ventricular pulsatile load. METHODS
      AND RESULTS: Several large clinical databases with right heart/pulmonary
      catheterization data were analyzed to determine the R(PA)-C(PA) relationship with
      pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary
      capillary wedge pressure. Patients with suspected or documented pulmonary
      hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a
      consistent R(PA)-C(PA) hyperbolic (inverse) dependence,
      C(PA)=0.564/(0.047+R(PA)), with a near-constant resistance-compliance product
      (0.48+/-0.17 seconds). In the same patients, the systemic resistance-compliance
      product was highly variable. Severe pulmonary fibrosis (n=89) did not change the
      R(PA)-C(PA) relation. Increasing patient age led to a very small but
      statistically significant change in the relation. However, elevation of the
      pulmonary capillary wedge pressure (n=8142) had a larger impact, significantly
      lowering C(PA) for any R(PA) and negatively correlating with the resistance
      compliance product (P<0.0001). CONCLUSIONS: Pulmonary hypertension and pulmonary
      fibrosis do not significantly change the hyperbolic dependence between R(PA) and
      C(PA), and patient age has only minimal effects. This fixed relationship helps
      explain the difficulty of reducing total right ventricular afterload by therapies
      that have a modest impact on mean R(PA). Higher pulmonary capillary wedge
      pressure appears to enhance net right ventricular afterload by elevating
      pulsatile, relative to resistive, load and may contribute to right ventricular
      dysfunction.

PMID- 22131358
TI  - Editorial: an apple a day keeps colitis away.

PMID- 22131359
TI  - Editorial: will the real neutrophil please stand up?

PMID- 22131360
TI  - Two-step generation of induced pluripotent stem cells from mouse fibroblasts
      using Id3 and Oct4.

PMID- 22131361
TI  - Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal
      kinesigenic choreoathetosis.
AB  - BACKGROUND: Paroxysmal kinesigenic choreoathetosis (PKC) is characterised by
      recurrent and brief attacks of involuntary movement, inherited as an autosomal
      dominant trait with incomplete penetrance. A PKC locus has been previously mapped
      to the pericentromeric region of chromosome 16 (16p11.2-q12.1), but the causative
      gene remains unidentified. METHODS/RESULTS: Deep sequencing of this 30 Mb region
      enriched with array capture in five affected individuals from four Chinese PKC
      families detected two heterozygous PRRT2 insertions (c.369dupG and c.649dupC),
      producing frameshifts and premature stop codons (p.S124VfsX10 and p.R217PfsX8,
      respectively) in two different families. Sanger sequencing confirmed these two
      mutations and revealed a missense PRRT2 mutation (c.859G->A, p.A287T) in one of
      the two remaining families. This study also sequenced PRRT2 in 29 sporadic cases
      affected with PKC and identified mutations in 10 cases, including six with the
      c.649dupC mutation. Most variants were truncating mutations, consistent with loss
      of-function and haploinsufficiency. CONCLUSION: The present study identifies
      PRRT2 as the gene mutated in a subset of PKC, and suggests that PKC is
      genetically heterogeneous.

PMID- 22131362
TI  - Inflammatory gout: observations over a half-century.
AB  - This is a discussion of acute gouty arthritis, seen for over 50 years of
      engagement. It addresses the evolution of our current understanding of the
      interaction between urate crystals and key cellular components of the gouty
      inflammatory paroxysm, with new material on pathogenesis.

PMID- 22131364
TI  - The pain of chronic Lyme disease: moving the discourse backward?

PMID- 22131365
TI  - Age differences in the effort and costs associated with cognitive activity.
AB  - OBJECTIVES: We tested the hypothesis that aging is associated with an increase in
      the effort and costs associated with cognitive activity using systolic blood
      pressure (SBP) as a measure of effort. METHOD: Younger and older adults engaged
      in an initial task (Phase 1) for 5 min that was relatively low (adding single
      digits) or high (subtracting by 3 s) in cognitive demands. They then solved a
      series of multiplication problems for 3 min (Phase 2). Cardiovascular measures
      were collected throughout, and reactivity was examined as a function of age,
      initial task difficulty, and test phase. RESULTS: Older adults exhibited higher
      levels of reactivity than younger adults to cognitive engagement, with reactivity
      increasing with task difficulty. Difficulty of the initial task was also
      associated with greater effort and lower performance on the subsequent
      multiplication task, suggestive of fatigue or depletion. These fatigue effects
      were stronger for older adults. DISCUSSION: The results were consistent with
      expectations and provided support for the utility of SBP reactivity as a measure
      of cognitive effort in studies of aging.

PMID- 22131366
TI  - Now departed from the Centers for Medicare and Medicaid Services, Berwick
      receives high marks for his tenure at agency.

PMID- 22131367
TI  - Existing health inequalities in India: informing preparedness planning for an
      influenza pandemic.
AB  - On 11 June 2009, the World Health Organization (WHO) declared that the world was
      in phase 6 of an influenza pandemic. In India, the first case of 2009 H1N1
      influenza was reported on 16 May 2009 and by August 2010 (when the pandemic was
      declared over), 38730 cases of 2009 H1N1 had been confirmed of which there were
      2024 deaths. Here, we propose a conceptual model of the sources of health
      disparities in an influenza pandemic in India. Guided by a published model of the
      plausible sources of such disparities in the United States, we reviewed the
      literature for the determinants of the plausible sources of health disparities
      during a pandemic in India. We find that factors at multiple social levels could
      determine inequalities in the risk of exposure and susceptibility to influenza,
      as well as access to treatment once infected: (1) religion, caste and indigenous
      identity, as well as education and gender at the individual level; (2) wealth at
      the household level; and (3) the type of location, ratio of health care
      practitioners to population served, access to transportation and public spending
      on health care in the geographic area of residence. Such inequalities could lead
      to unequal levels of disease and death. Whereas causal factors can only be
      determined by testing the model when incidence and mortality data, collected in
      conjunction with socio-economic and geographic factors, become available, we put
      forth recommendations that policy makers can undertake to ensure that the
      pandemic preparedness plan includes a focus on social inequalities in India in
      order to prevent their exacerbation in a pandemic.

PMID- 22131368
TI  - Replication of loci influencing ages at menarche and menopause in Hispanic women:
      the Women's Health Initiative SHARe Study.
AB  - Several genome-wide studies have identified loci associated with reproductive
      traits, such as ages of menarche and menopause, in women of European ancestry. In
      this study, we investigated the relevance of these loci in minority US Hispanic
      women. We utilized data from 3468 women who were genotyped as a part of the
      Women's Health Initiative SNP Health Association Resource. We replicated
      associations of eight loci (LRP18, LIN28B, CENPW, INHBA, TMEM38B, ZNF483, NFAT5
      and OLFM2) with age at menarche, and of two loci (MCM8 and BRSK1/TMEM150B) with
      age at menopause. The MCM8 locus was also associated with early menopause risk.
      Three loci (CENPW, MCM8 and BRSK1/TMEM150B) were associated with the length of
      reproductive lifespan. We provide evidence that genetic variants influencing
      reproductive traits identified in European populations are also important in
      minority US Hispanic women.

PMID- 22131370
TI  - Mechanisms underlying rule learning-induced enhancement of excitatory and
      inhibitory synaptic transmission.
AB  - Training rats to perform rapidly and efficiently in an olfactory discrimination
      task results in robust enhancement of excitatory and inhibitory synaptic
      connectivity in the rat piriform cortex, which is maintained for days after
      training. To explore the mechanisms by which such synaptic enhancement occurs, we
      recorded spontaneous miniature excitatory and inhibitory synaptic events in
      identified piriform cortex neurons from odor-trained, pseudo-trained, and naive
      rats. We show that olfactory discrimination learning induces profound enhancement
      in the averaged amplitude of AMPA receptor-mediated miniature synaptic events in
      piriform cortex pyramidal neurons. Such physiological modifications are apparent
      at least 4 days after learning completion and outlast learning-induced
      modifications in the number of spines on these neurons. Also, the averaged
      amplitude of GABA(A) receptor-mediated miniature inhibitory synaptic events was
      significantly enhanced following odor discrimination training. For both
      excitatory and inhibitory transmission, an increase in miniature postsynaptic
      current amplitude was evident in most of the recorded neurons; however, some
      neurons showed an exceptionally great increase in the amplitude of miniature
      events. For both excitatory and inhibitory transmission, the frequency of
      spontaneous synaptic events was not modified after learning. These results
      suggest that olfactory discrimination learning-induced enhancement of synaptic
      transmission in cortical neurons is mediated by postsynaptic modulation of AMPA
      receptor-dependent currents and balanced by long-lasting modulation of
      postsynaptic GABA(A) receptor-mediated currents.

PMID- 22131369
TI  - VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium
      homeostasis.
AB  - A proline to serine substitution at position 56 in the gene encoding vesicle
      associated membrane protein-associated protein B (VAPB) causes some dominantly
      inherited familial forms of motor neuron disease including amyotrophic lateral
      sclerosis (ALS) type-8. VAPB is an integral endoplasmic reticulum (ER) protein
      whose amino-terminus projects into the cytosol. Overexpression of ALS mutant
      VAPBP56S disrupts ER structure but the mechanisms by which it induces disease are
      not properly understood. Here we show that VAPB interacts with the outer
      mitochondrial membrane protein, protein tyrosine phosphatase-interacting protein
      51 (PTPIP51). ER and mitochondria are both stores for intracellular calcium
      (Ca(2+)) and Ca(2+) exchange between these organelles occurs at regions of ER
      that are closely apposed to mitochondria. These are termed mitochondria
      associated membranes (MAM). We demonstrate that VAPB is a MAM protein and that
      loss of either VAPB or PTPIP51 perturbs uptake of Ca(2+) by mitochondria
      following release from ER stores. Finally, we demonstrate that VAPBP56S has
      altered binding to PTPIP51 and increases Ca(2+) uptake by mitochondria following
      release from ER stores. Damage to ER, mitochondria and Ca(2+) homeostasis are all
      seen in ALS and we discuss the implications of our findings in this context.

PMID- 22131371
TI  - Late postnatal development of intrinsic and synaptic properties promotes fast and
      precise signaling in the dorsal nucleus of the lateral lemniscus.
AB  - The dorsal nucleus of the lateral lemniscus (DNLL) is an auditory brain stem
      structure that generates a long-lasting GABAergic output, which is important for
      binaural processing. Despite its importance in binaural processing, little is
      known about the cellular physiology and the synaptic input kinetics of DNLL
      neurons. To assess the relevant physiological parameters of DNLL neurons, their
      late postnatal developmental profile was analyzed in acute brain slices of 9- to
      26-day-old Mongolian gerbils. The observed developmental changes in passive
      membrane and action potential (AP) properties all point toward an improvement of
      fast and precise signal integration in these neurons. Accordingly, synaptic
      glutamatergic and GABAergic current kinetics accelerate with age. The changes in
      intrinsic and synaptic properties contribute nearly equally to reduce the latency
      and jitter in AP generation and thus enhance the temporal precision of DNLL
      neurons. Furthermore, the size of the synaptic NMDA current is developmentally
      downregulated. Despite this developmental reduction, DNLL neurons display an NMDA
      dependent postsynaptic amplification of AP generation, known to support high
      firing rates, throughout this developmental period. Taken together, our findings
      indicate that during late postnatal development DNLL neurons are optimized for
      high firing rates with high temporal precision.

PMID- 22131373
TI  - Interhemispheric connectivity between distinct motor regions as a window into
      bimanual coordination.
AB  - Performing coordinated bimanual movement is a fundamental feature of the human
      motor system, with imaging techniques revealing the involvement of an extensive
      network of motor regions in both hemispheres. Using transcranial magnetic
      stimulation, Liuzzi et al. (J Neurosci 31: 9111-9117, 2011) recently extended our
      understanding of the neural correlates of motor actions by showing that the
      nature of the interhemispheric connectivity between primary and premotor regions
      may influence motor performance during a bimanual tapping task.

PMID- 22131372
TI  - Sound-identity processing in early areas of the auditory ventral stream in the
      macaque.
AB  - Auditory cortical processing is thought to be accomplished along two processing
      streams. The existence of a posterior/dorsal stream dealing, among others, with
      the processing of spatial aspects of sound has been corroborated by numerous
      studies in several species. An anterior/ventral stream for the processing of
      nonspatial sound qualities, including the identification of sounds such as
      species-specific vocalizations, has also received much support. Originally
      discovered in anterolateral belt cortex, most recent work on the anterior/ventral
      pathway has been performed on far anterior superior temporal (ST) areas and on
      ventrolateral prefrontal cortex (VLPFC). Regions of the anterior/ventral stream
      near its origin in early auditory areas have been less explored. In the present
      study, we examined three early auditory regions with different anteroposterior
      locations (caudal, middle, and rostral) in awake rhesus macaques. We analyzed how
      well classification based on sound-evoked activity patterns of neuronal
      populations replicates the original stimulus categories. Of the three regions,
      the rostral region (rR), which included core area R and medial belt area RM,
      yielded the greatest classification success across all stimulus classes or
      between classes of natural sounds. Starting from ~80 ms past stimulus onset,
      clustering based on the population response in rR became clearly more successful
      than clustering based on responses from any other region. Our study demonstrates
      that specialization for sound-identity processing can be found very early in the
      auditory ventral stream. Furthermore, the fact that this processing develops over
      time can shed light on underlying mechanisms. Finally, we show that population
      analysis is a more sensitive method for revealing functional specialization than
      conventional types of analysis.

PMID- 22131374
TI  - P2Y1 receptor modulation of Ca2+-activated K+ currents in medium-sized neurons
      from neonatal rat striatal slices.
AB  - ATP signaling to neurons and glia in the nervous system occurs via activation of
      both P2Y and P2X receptors. Here, we investigated the effects of P2Y(1) receptor
      stimulation in developing striatal medium-sized neurons using patch-clamp
      recordings from acute brain slices of 7- and 28-day-old rats. Application of the
      selective P2Y(1) receptor agonist 2-(Methylthio) ADP trisodium salt (2-MeSADP;
      250 nM) increased outward K(+) currents evoked by a ramp depolarization protocol
      in voltage-clamp recordings. This effect was observed in 59 out of 82 cells (72%)
      and was blocked completely by the P2Y(1) antagonist, 2'-deoxy-N(6)-methyl
      adenosine 3',5'-diphosphate. The averaged 2-MeSADP-sensitive conductance was
      fitted by the sum of a linear conductance and a Boltzmann relation, giving one
      half activation voltage of -14.2 mV and an equivalent charge of 2.91. The 2MeSADP
      mediated effect was sensitive to submillimolar concentrations of
      tetraethylammonium (TEA; 200 MUM), to 200 nM iberiotoxin and to 100 nM apamin,
      suggesting the involvement of both big and small potassium (BK and SK,
      respectively) calcium-activated channels. In current-clamp experiments, 2-MeSADP
      decreased depolarization-evoked action potential (AP) firing in all 26 cells
      investigated, and this effect was reversed by TEA and by apamin but not by
      iberiotoxin. We conclude that the stimulation of P2Y(1) receptors in developing
      striatal neurons leads to activation of calcium-activated potassium channels
      [I(K(Ca))] of both BK and SK subtypes, the latter responsible for decreasing the
      frequency of AP firing in response to current injection. Therefore, P2Y(1)
      signaling leading to activation of I(K(Ca)) may be important in regulating the
      activity of medium-sized neurons in the striatum.

PMID- 22131376
TI  - Physical model of coherent potentials measured with different electrode recording
      site sizes.
AB  - A question that still complicates interpretation of local field potentials (LFPs)
      is how electrode properties like impedance, size, and shape affect recorded LFPs.
      In addition, how any such effects should be considered when comparing LFP,
      electroencephalogram (EEG), or electrocorticogram (ECoG) data has not been
      clearly described. A generally accepted concrete physical model describes that an
      electrode records the spatial average of the voltage across its uninsulated tip,
      yet the effects of this spatial averaging on recorded coherence have never been
      modeled. Using simulations based on this physical model, we show here that for
      any effects to occur, a spatial voltage gradient on a scale smaller than an
      electrode's recording site must exist over the site's surface. When this occurs,
      larger electrodes on average report higher coherence between locations, with the
      effect continuously increasing as the voltage profile over the extent of the
      recording site is increasingly nonuniform. We quantitatively compared published
      coherence estimates of LFP, ECoG, and EEG data across a range of studies and
      found a possible modest effect of electrode size in published ECoG data only. We
      used the model to quantify the expected coherence for any electrode size in
      relation to any given spatial frequency of a voltage profile. From this and
      existing estimates of the spread of voltages underlying each of these data types,
      our simulations quantitatively agree with the published data and importantly
      suggest that LFP coherence will be independent of recording site size within the
      range of microelectrodes typically used for extracellular recordings.

PMID- 22131375
TI  - Reorganization in processing of spectral and temporal input in the rat posterior
      auditory field induced by environmental enrichment.
AB  - Environmental enrichment induces powerful changes in the adult cerebral cortex.
      Studies in primary sensory cortex have observed that environmental enrichment
      modulates neuronal response strength, selectivity, speed of response, and
      synchronization to rapid sensory input. Other reports suggest that nonprimary
      sensory fields are more plastic than primary sensory cortex. The consequences of
      environmental enrichment on information processing in nonprimary sensory cortex
      have yet to be studied. Here we examine physiological effects of enrichment in
      the posterior auditory field (PAF), a field distinguished from primary auditory
      cortex (A1) by wider receptive fields, slower response times, and a greater
      preference for slowly modulated sounds. Environmental enrichment induced a
      significant increase in spectral and temporal selectivity in PAF. PAF neurons
      exhibited narrower receptive fields and responded significantly faster and for a
      briefer period to sounds after enrichment. Enrichment increased time-locking to
      rapidly successive sensory input in PAF neurons. Compared with previous
      enrichment studies in A1, we observe a greater magnitude of reorganization in PAF
      after environmental enrichment. Along with other reports observing greater
      reorganization in nonprimary sensory cortex, our results in PAF suggest that
      nonprimary fields might have a greater capacity for reorganization compared with
      primary fields.

PMID- 22131378
TI  - Stiffness, not inertial coupling, determines path curvature of wrist motions.
AB  - When humans rotate their wrist in flexion-extension, radial-ulnar deviation, and
      combinations, the resulting paths (like the path of a laser pointer on a screen)
      exhibit a distinctive pattern of curvature. In this report we show that the
      passive stiffness of the wrist is sufficient to account for this pattern.
      Simulating the dynamics of wrist rotations using a demonstrably realistic model
      under a variety of conditions, we show that wrist stiffness can explain all
      characteristics of the observed pattern of curvature. We also provide evidence
      against other possible causes. We further demonstrate that the phenomenon is
      robust against variations in human wrist parameters (inertia, damping, and
      stiffness) and choice of model inputs. Our findings explain two previously
      observed phenomena: why faster wrist rotations exhibit more curvature and why
      path curvature rotates with pronation-supination of the forearm. Our results
      imply that, as in reaching, path straightness is a goal in the planning and
      control of wrist rotations. This requires humans to predict and compensate for
      wrist dynamics, but, unlike reaching, nonlinear inertial coupling (e.g., Coriolis
      acceleration) is insignificant. The dominant term to be compensated is wrist
      stiffness.

PMID- 22131377
TI  - Human inferior colliculus activity relates to individual differences in spoken
      language learning.
AB  - A challenge to learning words of a foreign language is encoding nonnative
      phonemes, a process typically attributed to cortical circuitry. Using multimodal
      imaging methods [functional magnetic resonance imaging-adaptation (fMRI-A) and
      auditory brain stem responses (ABR)], we examined the extent to which pretraining
      pitch encoding in the inferior colliculus (IC), a primary midbrain structure,
      related to individual variability in learning to successfully use nonnative pitch
      patterns to distinguish words in American English-speaking adults. fMRI-A indexed
      the efficiency of pitch representation localized to the IC, whereas ABR
      quantified midbrain pitch-related activity with millisecond precision. In line
      with neural "sharpening" models, we found that efficient IC pitch pattern
      representation (indexed by fMRI) related to superior neural representation of
      pitch patterns (indexed by ABR), and consequently more successful word learning
      following sound-to-meaning training. Our results establish a critical role for
      the IC in speech-sound representation, consistent with the established role for
      the IC in the representation of communication signals in other animal models.

PMID- 22131379
TI  - Closely overlapping responses to tools and hands in left lateral occipitotemporal
      cortex.
AB  - The perception of object-directed actions performed by either hands or tools
      recruits regions in left fronto-parietal cortex. Here, using functional MRI
      (fMRI), we tested whether the common role of hands and tools in object
      manipulation is also reflected in the distribution of response patterns to these
      categories in visual cortex. In two experiments we found that static pictures of
      hands and tools activated closely overlapping regions in left lateral
      occipitotemporal cortex (LOTC). Left LOTC responses to tools selectively
      overlapped with responses to hands but not with responses to whole bodies,
      nonhand body parts, other objects, or visual motion. Multivoxel pattern analysis
      in left LOTC indicated a high degree of similarity between response patterns to
      hands and tools but not between hands or tools and other body parts. Finally,
      functional connectivity analysis showed that the left LOTC hand/tool region was
      selectively connected, relative to neighboring body-, motion-, and object
      responsive regions, with regions in left intraparietal sulcus and left premotor
      cortex that have previously been implicated in hand/tool action-related
      processing. Taken together, these results suggest that action-related object
      properties shared by hands and tools are reflected in the organization of high
      order visual cortex. We propose that the functional organization of high-order
      visual cortex partly reflects the organization of downstream functional networks,
      such as the fronto-parietal action network, due to differences within visual
      cortex in the connectivity to these networks.

PMID- 22131380
TI  - Attentional control of sensory tuning in human visual perception.
AB  - Attention is known to affect the response properties of sensory neurons in visual
      cortex. These effects have been traditionally classified into two categories: 1)
      changes in the gain (overall amplitude) of the response; and 2) changes in the
      tuning (selectivity) of the response. We performed an extensive series of
      behavioral measurements using psychophysical reverse correlation to understand
      whether/how these neuronal changes are reflected at the level of our perceptual
      experience. This question has been addressed before, but by different
      laboratories using different attentional manipulations and stimuli/tasks that are
      not directly comparable, making it difficult to extract a comprehensive and
      coherent picture from existing literature. Our results demonstrate that the
      effect of attention on response gain (not necessarily associated with tuning
      change) is relatively aspecific: it occurred across all the conditions we tested,
      including attention directed to a feature orthogonal to the primary feature for
      the assigned task. Sensory tuning, however, was affected primarily by feature
      based attention and only to a limited extent by spatially directed attention, in
      line with existing evidence from the electrophysiological and behavioral
      literature.

PMID- 22131381
TI  - Synaptic release and extracellular actions of Zn2+ limit propagation of spreading
      depression and related events in vitro and in vivo.
AB  - Cortical spreading depression (CSD) is a consequence of a slowly propagating wave
      of neuronal and glial depolarization (spreading depolarization; SD). Massive
      release of glutamate contributes to SD propagation, and it was recently shown
      that Zn(2+) is also released from synaptic vesicles during SD. The present study
      examined consequences of extracellular Zn(2+) accumulation on the propagation of
      SD. SD mechanisms were studied first in murine brain slices, using focal KCl
      applications as stimuli and making electrical and optical recordings in
      hippocampal area CA1. Elevating extracellular Zn(2+) concentrations with
      exogenous ZnCl(2) reduced SD propagation rates. Selective chelation of endogenous
      Zn(2+) (using TPEN or CaEDTA) increased SD propagation rates, and these effects
      appeared due to chelation of Zn(2+) derived from synaptic vesicles. Thus, in
      tissues where synaptic Zn(2+) release was absent [knockout (KO) of vesicular
      Zn(2+) transporter ZnT-3], SD propagation rates were increased, and no additional
      increase was observed following chelation of endogenous Zn(2+) in these tissues.
      The role of synaptic Zn(2+) was then examined on CSD in vivo. ZnT-3 KO animals
      had higher susceptibility to CSD than wild-type controls as evidenced by
      significantly higher propagation rates and frequencies. Studies of candidate
      mechanisms excluded changes in neuronal excitability, presynaptic release, and
      GABA receptors but left open a possible contribution of N-methyl-d-aspartate
      (NMDA) receptor inhibition. These results suggest the extracellular accumulation
      of synaptically released Zn(2+) can serve as an intrinsic inhibitor to limit SD
      events. The inhibitory action of extracellular Zn(2+) on SD may counteract to
      some extent the neurotoxic effects of intracellular Zn(2+) accumulation in acute
      brain injury models.

PMID- 22131383
TI  - Functional localization of neurotransmitter receptors and synaptic inputs to
      mature neurons of the medial superior olive.
AB  - Neurons of the medial superior olive (MSO) code for the azimuthal location of low
      frequency sound sources via a binaural coincidence detection system operating on
      microsecond time scales. These neurons are morphologically simple and
      stereotyped, and anatomical studies have indicated a functional segregation of
      excitatory and inhibitory inputs between cellular compartments. It is thought
      that this morphological arrangement holds important implications for the
      computational task of these cells. To date, however, there has been no functional
      investigation into synaptic input sites or functional receptor distributions on
      mature neurons of the MSO. Here, functional neurotransmitter receptor maps for
      amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA), N-methyl-D-aspartate
      (NMDA), glycine (Gly), and ionotropic gamma-aminobutyric acid (GABA(A)) receptors
      (Rs) were compared and complemented by their corresponding synaptic input map. We
      find in MSO neurons from postnatal day 20-35 gerbils that AMPARs and their
      excitatory inputs target the soma and dendrites. Functional GlyRs and their
      inhibitory inputs are predominantly refined to the somata, although a pool of
      functional GlyRs is present extrasynaptically on MSO dendrites. GABA(A)R
      responses are present throughout the cell but lack direct synaptic contact
      indicating an involvement in volume transmission. NMDARs are present both
      synaptically and extrasynaptically with an overall distribution similar to GlyRs.
      Interestingly, even at physiological temperatures these functional NMDARs can be
      potentiated by synaptically released Gly. The functional receptor and synaptic
      input maps produced here led to the identification of a cross talk between
      transmitter systems and raises the possibility that extrasynaptic receptors could
      be modulating leak conductances as a homeostatic mechanism.

PMID- 22131382
TI  - Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and
      Parkinsonian monkeys.
AB  - According to traditional models of the basal ganglia-thalamocortical network of
      connections, dopamine exerts D2-like receptor (D2LR)-mediated effects through
      actions on striatal neurons that give rise to the "indirect" pathway, secondarily
      affecting the activity in the internal and external pallidal segments (GPi and
      GPe, respectively) and the substantia nigra pars reticulata (SNr). However,
      accumulating evidence from the rodent literature suggests that D2LR activation
      also directly influences synaptic transmission in these nuclei. To further
      examine this issue in primates, we combined in vivo electrophysiological
      recordings and local intracerebral microinjections of drugs with electron
      microscopic immunocytochemistry to study D2LR-mediated modulation of neuronal
      activities in GPe, GPi, and SNr of normal and MPTP-treated (parkinsonian)
      monkeys. D2LR activation with quinpirole increased firing in most GPe neurons,
      likely due to a reduction of striatopallidal GABAergic inputs. In contrast, local
      application of quinpirole reduced firing in GPi and SNr, possibly through D2LR
      mediated effects on glutamatergic inputs. Injections of the D2LR antagonist
      sulpiride resulted in effects opposite to those of quinpirole in GPe and GPi. D2
      receptor immunoreactivity was most prevalent in putative striatal-like GABAergic
      terminals and unmyelinated axons in GPe, GPi, and SNr, but a significant
      proportion of immunoreactive boutons also displayed ultrastructural features of
      glutamatergic terminals. Postsynaptic labeling was minimal in all nuclei. The
      D2LR-mediated effects and pattern of distribution of D2 receptor immunoreactivity
      were maintained in the parkinsonian state. Thus, in addition to their
      preferential effects on indirect pathway striatal neurons, extrastriatal D2LR
      activation in GPi and SNr also influences direct pathway elements in the primate
      basal ganglia under normal and parkinsonian conditions.

PMID- 22131384
TI  - mGluR6 deletion renders the TRPM1 channel in retina inactive.
AB  - In darkness, glutamate released from photoreceptors activates the metabotropic
      glutamate receptor 6 (mGluR6) on retinal ON bipolar cells. This activates the G
      protein G(o), which then closes transient receptor potential melastatin 1 (TRPM1)
      channels, leading to cells' hyperpolarization. It has been generally assumed that
      deleting mGluR6 would render the cascade inactive and the ON bipolar cells
      constitutively depolarized. Here we show that the rod bipolar cells in mGluR6
      null mice were hyperpolarized. The slope conductance of the current-voltage
      curves and the current noise were smaller than in wild type. Furthermore, while
      in wild-type rod bipolar cells, TRPM1 could be activated by local application of
      capsaicin; in null cells, it did not. These results suggest that the TRPM1
      channel in mGluR6-null rod bipolar cells is inactive. To explore the reason for
      this lack of activity, we tested if mGluR6 deletion affected expression of
      cascade components. Immunostaining for G protein subunit candidates Galpha(o),
      Gbeta(3), and Ggamma(13) showed no significant changes in their expression or
      distribution. Immunostaining for TRPM1 in the dendritic tips was greatly reduced,
      but the channel was still present in the soma and primary dendrites of mGluR6
      null bipolar cells, where a certain fraction of TRPM1 appears to localize to the
      plasma membrane. Consequently, the lack of TRPM1 activity in the null retina is
      unlikely to be due to failure of the channels to localize to the plasma membrane.
      We speculate that, to be constitutively active, TRPM1 channels in ON bipolar
      cells have to be in a complex, or perhaps require an unidentified factor.

PMID- 22131385
TI  - Facilitation of learning induced by both random and gradual visuomotor task
      variation.
AB  - Motor task variation has been shown to be a key ingredient in skill transfer,
      retention, and structural learning. However, many studies only compare training
      of randomly varying tasks to either blocked or null training, and it is not clear
      how experiencing different nonrandom temporal orderings of tasks might affect the
      learning process. Here we study learning in human subjects who experience the
      same set of visuomotor rotations, evenly spaced between -60 degrees  and +60
      degrees , either in a random order or in an order in which the rotation angle
      changed gradually. We compared subsequent learning of three test blocks of +30
      degrees ->-30 degrees ->+30 degrees  rotations. The groups that underwent either
      random or gradual training showed significant (P < 0.01) facilitation of learning
      in the test blocks compared with a control group who had not experienced any
      visuomotor rotations before. We also found that movement initiation times in the
      random group during the test blocks were significantly (P < 0.05) lower than for
      the gradual or the control group. When we fit a state-space model with fast and
      slow learning processes to our data, we found that the differences in performance
      in the test block were consistent with the gradual or random task variation
      changing the learning and retention rates of only the fast learning process. Such
      adaptation of learning rates may be a key feature of ongoing meta-learning
      processes. Our results therefore suggest that both gradual and random task
      variation can induce meta-learning and that random learning has an advantage in
      terms of shorter initiation times, suggesting less reliance on cognitive
      processes.

PMID- 22131386
TI  - Nitric oxide activates hypoglossal motoneurons by cGMP-dependent inhibition of
      TASK channels and cGMP-independent activation of HCN channels.
AB  - Nitric oxide (NO) is an important signaling molecule that regulates numerous
      physiological processes, including activity of respiratory motoneurons. However,
      molecular mechanism(s) underlying NO modulation of motoneurons remain obscure.
      Here, we used a combination of in vivo and in vitro recording techniques to
      examine NO modulation of motoneurons in the hypoglossal motor nucleus (HMN).
      Microperfusion of diethylamine (DEA; an NO donor) into the HMN of anesthetized
      adult rats increased genioglossus muscle activity. In the brain slice, whole cell
      current-clamp recordings from hypoglossal motoneurons showed that exposure to DEA
      depolarized membrane potential and increased responsiveness to depolarizing
      current injections. Under voltage-clamp conditions, we found that NO inhibited a
      Ba(2+)-sensitive background K(+) conductance and activated a Cs(+)-sensitive
      hyperpolarization-activated inward current (I(h)). When I(h) was blocked with
      Cs(+) or ZD-7288, the NO-sensitive K(+) conductance exhibited properties similar
      to TWIK-related acid-sensitive K(+) (TASK) channels, i.e., voltage independent,
      resistant to tetraethylammonium and 4-aminopyridine but inhibited by
      methanandamide. The soluble guanylyl cyclase blocker 1H-(1,2,4)oxadiazole(4,3
      a)quinoxaline-1-one (ODQ) and the PKG blocker KT-5823 both decreased NO
      modulation of this TASK-like conductance. To characterize modulation of I(h) in
      relative isolation, we tested effects of NO in the presence of Ba(2+) to block
      TASK channels. Under these conditions, NO activated both the instantaneous
      (I(inst)) and time-dependent (I(ss)) components of I(h). Interestingly, at more
      hyperpolarized potentials NO preferentially increased I(inst). The effects of NO
      on I(h) were retained in the presence of ODQ and blocked by the cysteine-specific
      oxidant N-ethylmaleimide. These results suggest that NO activates hypoglossal
      motoneurons by cGMP-dependent inhibition of a TASK-like current and S
      nitrosylation-dependent activation of I(h).

PMID- 22131387
TI  - Subfertility and risk of later life maternal cardiovascular disease.
AB  - BACKGROUND: Subfertility shares common pathways with cardiovascular disease
      (CVD), including polycystic ovarian syndrome, obesity and thyroid disorders.
      Women with prior 0-1 pregnancies are at an increased risk of incident CVD when
      compared with women with two pregnancies. It is uncertain whether history of
      subfertility among women eventually giving birth is a risk factor for CVD.
      METHODS: Among Swedish women with self-reported data on subfertility in the
      Swedish Medical Birth Register (n = 863 324), we used Cox proportional hazards
      models to relate a history of subfertility to CVD risk after adjustment for age,
      birth year, highest income, education, birth country, hypertension, diabetes,
      preterm birth, small for gestational age (SGA), smoking and for BMI in separate
      models. In additional analyses, we excluded women with: (i) pregnancy-related or
      non-pregnancy-related hypertension and/or diabetes; and (ii) preterm births
      and/or SGA babies. RESULTS: Among nulliparous women eventually having a
      childbirth (between 1983 and 2005, the median follow-up time 11.9; 0-23 years and
      9 906 621 person-years of follow-up), there was an increased risk of CVD among
      women reporting >= 5 years of subfertility versus 0 years (hazard ratio 1.19, 95%
      confidence interval 1.02-1.39). There were not significantly elevated CVD risks
      for women with 1-2 or 3-4 years of subfertility versus 0 years. Accounting for
      BMI did not change results. Excluding women with hypertension and/or diabetes
      attenuated associations, whereas exclusion of women with preterm and/or SGA
      births did not change findings. CONCLUSIONS Subfertility among women eventually
      having a childbirth is a risk factor for CVD even upon accounting for
      cardiovascular risk factors and adverse pregnancy outcomes. Future studies should
      explore the mechanisms underlying this association.

PMID- 22131388
TI  - The decline of fertility in male uremic patients is correlated with low
      expression of the cystic fibrosis transmembrane conductance regulator protein
      (CFTR) in human sperm.
AB  - BACKGROUND: The present study was designed to investigate the possible
      association between infertility of male uremic patients and expression of the
      cystic fibrosis transmembrane conductance regulator (CFTR) protein in their
      sperm. METHODS: Semen was collected and analyzed. Serum levels of FSH, LH and
      testosterone were measured by radioimmunoassay. The sperm CFTR expressions of 21
      uremic patients and 15 renal transplant patients were measured and compared with
      those of 32 healthy and 33 infertile men. RESULTS: Only 9 +/- 5.9% of sperm from
      uremic patients expressed CFTR, significantly less than those of the renal
      transplant patients (29 +/- 14.3%, P< 0.001), the infertile men (42 +/- 20.7%, P<
      0.001) and the healthy men (51 +/- 20.5%, P< 0.001). Furthermore, significantly
      fewer sperm from renal transplant patients expressed CFTR than those of the
      infertile men (P< 0.05) and the healthy men (P< 0.01). LH levels in uremic
      patients were significantly higher than in all other groups, whereas FSH levels
      in uremic patients were only significantly higher than in infertile and healthy
      men. There was no significant difference in testosterone level among the four
      categories. CONCLUSIONS: Sperm CFTR expression is depressed in uremic patients
      but recovers to some degree after renal transplant along with some improvement in
      fertility, indicating a 'reversible' change. These results suggest that the CFTR
      expression rate in sperm is correlated with the decline of uremic patients'
      fertility, and may be considered as a potential marker to assess the fertility of
      male uremic patients.

PMID- 22131389
TI  - Monitoring of ovarian activity by measurement of urinary excretion rates of
      estrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part
      II: reliability of home testing.
AB  - BACKGROUND: The UNDP/WHO/World Bank/Special Programme of Research, Development
      and Research Training in Human Reproduction (Geneva) set up a study to determine
      whether it is feasible for women to monitor their ovarian activity reliably by
      home testing. Daily self-monitoring of urinary hormone metabolites for menstrual
      cycle assessment was evaluated by comparison of results obtained with the Home
      Ovarian Monitor by untrained users both at home and in study centres. METHODS:
      Women collected daily data for urinary estrone glucuronide (E1G) and pregnanediol
      glucuronide (PdG) for two cycles, then the procedure was repeated in the women's
      local centre (in Chile, Australia or New Zealand) giving a total of 113 duplicate
      cycles. The tests were performed without the benefit of replicates or quality
      controls. The home and centre cycles were normalized and compared to identify
      assay errors, and the resulting home and centre menstrual cycle profiles were
      averaged. RESULTS: Reliable mean cycle profiles were obtained with the home and
      centre excretion rates agreeing to within 36 +/- 21 nmol/24 h for E1G and 0.77 +/
      0.28 umol/24 h for baseline PdG values (1-5 umol/24 h). The cycles had a mean
      length of 28.1 +/- 3.1 days (n = 112; 5th and 95th percentiles: 24 and 35 days,
      respectively), a mean follicular phase of 14.8 +/- 3.1 days (n = 107; 5th and
      95th percentiles: 11 and 21 days) and a mean luteal phase length of 13.3 +/- 1.5
      days (n = 106; 5th and 95th percentiles: 11 and 17 days), calculated from the day
      of the LH peak. CONCLUSIONS: The study confirmed that the Ovarian Monitor pre
      coated assay tubes worked well even in the hands of lay users, without standard
      curves, quality controls or replicates. Point-of-care monitoring to give reliable
      fertility data is feasible.

PMID- 22131390
TI  - Investigation of systemic inflammatory response in first trimester pregnancy
      failure.
AB  - BACKGROUND: The contribution of local and systemic inflammation to the
      pathophysiology of sporadic first trimester miscarriages remains unclear. The
      objective of this study was to investigate the inflammatory response in the
      circulation of women presenting with first trimester miscarriage. METHODS: Levels
      of tumour necrosis factor alpha (TNFalpha), TNF receptors 1 and 2, interferon
      gamma (IFNgamma), interleukin (IL)-6 and IL-10 were assayed using cytometric bead
      arrays in plasma samples from 29 euploid and 21 aneuploid missed miscarriages, 35
      normal pregnant controls and 31 non-pregnant women (NPW). Whole blood flow
      cytometry was carried out with samples from 17 euploid and 16 aneuploid
      miscarriages, 18 pregnant controls and 13 NPW. RESULTS: The plasma of women with
      euploid miscarriage contained significantly higher circulating levels of TNFalpha
      (P < 0.005), IFNgamma (P < 0.005), IL-6 (P < 0.005) and IL-10 (P < 0.01) than
      that of pregnant controls, irrespective of gestational age. Significantly (P <
      0.05) higher TNF-R1 levels at 6-9 weeks, and significantly higher TNFalpha/IL-6
      (P < 0.001) and significantly lower TNFalpha/IL-10 (P < 0.001) and IFNgamma/IL-10
      (P < 0.001) ratios at 10-14 weeks, were also found in euploid miscarriage cases
      compared with pregnant controls. TNFalpha/IL-10 ratio in plasma was significantly
      (P < 0.05) lower in miscarriages with an abnormal karyotype than those with
      normal karyotype. Normal pregnant women had a significantly higher plasma level
      of IFNgamma (P < 0.01) and IFNgamma/IL-10 ratio (P < 0.005), a significantly (P <
      0.005) lower TNF-R1 level, and a significant (P < 0.05) increase in stimulated
      TNFalpha in monocytes, compared with NPW. CONCLUSIONS: Our data confirm that
      there is an inflammatory reaction in normal pregnancy compared with the non
      pregnant state, which may be disrupted during miscarriage.

PMID- 22131392
TI  - Experimental endoscopic endovascular cannulation: a novel approach to
      thrombolysis in retinal vessel occlusion.
AB  - PURPOSE: Recent studies suggest that the cannulation of retinal vessels may
      provide a potential access route for the administration of thrombolytic agents in
      retinal vessel occlusion. However, the major problem with available techniques is
      the limited visualization of retinal vessels with conventional surgical
      microscopes, making it difficult to effectively control the targeted injection of
      drugs. METHODS: The authors developed a novel single-piece catheter system for
      the endoscopically guided puncture of microvessels. Experimental punctures of
      retinal vessels with injection of fluid were performed in porcine cadaver eyes
      using a standard high-resolution gradient index microendoscope introduced through
      the pars plana. RESULTS: Endoscopically guided punctures were successfully
      performed in porcine branch retinal veins at various distances from the optic
      disc. Injection of recombinant tissue plasminogen activator (rt-PA), hypertonic
      solution (hyper HES), or normal saline solution into the vessel lumen was
      accomplished under direct endoscopic view in a safe and reliable manner.
      CONCLUSIONS: Endoscopically guided puncture of retinal microvessels is feasible
      and can be performed through a pars plana entry without additional
      micromanipulation devices. This novel technique may be a safe and effective
      approach to catheter-directed endovascular thrombolysis in retinal vascular
      occlusive diseases.

PMID- 22131391
TI  - Differences in human meibum lipid composition with meibomian gland dysfunction
      using NMR and principal component analysis.
AB  - PURPOSE: Nuclear magnetic resonance (NMR) spectroscopy has been used to quantify
      lipid wax, cholesterol ester terpenoid and glyceride composition, saturation,
      oxidation, and CH2 and CH3 moiety distribution. This tool was used to measure
      changes in human meibum composition with meibomian gland dysfunction (MGD).
      METHODS: (1)H-NMR spectra of meibum from 39 donors with meibomian gland
      dysfunction (Md) were compared to meibum from 33 normal donors (Mn). RESULTS:
      Principal component analysis (PCA) was applied to the CH2/CH3 regions of a set of
      training NMR spectra of human meibum. PCA discriminated between Mn and Md with an
      accuracy of 86%. There was a bias toward more accurately predicting normal
      samples (92%) compared with predicting MGD samples (78%). When the NMR spectra of
      Md were compared with those of Mn, three statistically significant decreases were
      observed in the relative amounts of CH3 moieties at 1.26 ppm, the products of
      lipid oxidation above 7 ppm, and the =CH moieties at 5.2 ppm associated with
      terpenoids. CONCLUSIONS: Loss of the terpenoids could be deleterious to meibum
      since they exhibit a plethora of mostly positive biological functions and could
      account for the lower level of cholesterol esters observed in Md compared with
      Mn. All three changes could account for the higher degree of lipid order of Md
      compared with age-matched Mn. In addition to the power of NMR spectroscopy to
      detect differences in the composition of meibum, it is promising that NMR can be
      used as a diagnostic tool.

PMID- 22131393
TI  - An optical coherence tomography study on degeneration of retinal nerve fiber
      layer in rats with autoimmune optic neuritis.
AB  - PURPOSE: The aim of the present study was to evaluate the ability and accuracy of
      spectral domain optical coherence tomography (OCT) for in vivo monitoring of
      retinal ganglion cell degeneration in a rat model of myelin oligodendrocyte
      glycoprotein-induced optic neuritis. METHODS: First, OCT imaging was established
      for imaging of all retinal layers in Brown Norway rats. Second, thickness
      measurements of retinal nerve fiber layer (RNFL) were performed by periodically
      imaging during the development and progression of autoimmune optic neuritis.
      Third, the reproducibility of OCT measurements was determined by comparing RNFL
      measurements of two independent investigators. Fourth, OCT data were correlated
      with histopathology obtained ex vivo after the final imaging session. RESULTS:
      Results showed that RNFL thickness declined significantly before clinical
      manifestation of the disease and decline progresses continuously during the
      disease course. RNFL thickness measured by OCT had good repeatability and also
      corresponded with histomorphometric measurements. The reproducibility was limited
      because of the post-processing analyses performed by manual measurements.
      CONCLUSIONS: In summary, it is shown here for the first time that OCT can
      reliably monitor neurodegeneration in an experimental model of autoimmune optic
      neuritis in rodents. Moreover, in comparing RNFL thickness decline with
      histopathological analyses of the optic nerve, these results suggest an early,
      and in part, inflammation-independent process of RNFL degeneration in autoimmune
      optic neuritis.

PMID- 22131394
TI  - A single-base substitution in the seed region of miR-184 causes EDICT syndrome.
AB  - PURPOSE: To investigate the cause of the syndrome characterized by endothelial
      dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT).
      METHODS: Previously a multigenerational family was reported that comprised 10
      individuals affected by syndromal anterior segment dysgenesis. Blood samples were
      re-collected from eight affected and two unaffected individuals, and genomic DNA
      was extracted. A total of 24 candidate genes and 4 microRNAs residing within the
      critical interval were sequenced bidirectionally. In silico analyses were
      performed to examine the effect of the causal variant on the stability of the pre
      microRNA structure. RESULTS: Bidirectional sequencing identified the single-base
      substitution +57C>T in miR-184. This variation segregated with the disease
      phenotype and was absent in the 1000 Genomes project, 1130 control chromosomes,
      and 28 nonhuman vertebrates. CONCLUSIONS: The single-base-pair substitution in
      the seed region of miR-184 is responsible for the disease phenotype observed in
      EDICT syndrome.

PMID- 22131395
TI  - Recessive loss-of-function mutation in the pacemaker HCN2 channel causing
      increased neuronal excitability in a patient with idiopathic generalized
      epilepsy.
AB  - The hyperpolarization-activated I(h) current, coded for by hyperpolarization
      activated, cyclic nucleotide-gated (HCN) channels, controls synaptic integration
      and intrinsic excitability in many brain areas. Because of their role in
      pacemaker function, defective HCN channels are natural candidates for
      contributing to epileptogenesis. Indeed, I(h) is pathologically altered after
      experimentally induced seizures, and several independent data indicate a link
      between dysfunctional HCN channels and different forms of epilepsy. However,
      direct evidence for functional changes of defective HCN channels correlating with
      the disease in human patients is still elusive. By screening families with
      epilepsy for mutations in Hcn1 and Hcn2 genes, we found a recessive loss-of
      function point mutation in the gene coding for the HCN2 channel in a patient with
      sporadic idiopathic generalized epilepsy. Of 17 screened members of the same
      family, the proband was the only one affected and homozygous for the mutation.
      The mutation (E515K) is located in the C-linker, a region known to affect channel
      gating. Functional analysis revealed that homomeric mutant, but not heteromeric
      wild-type/mutant channels, have a strongly inhibited function caused by a large
      negative shift of activation range and slowed activation kinetics, effectively
      abolishing the HCN2 contribution to activity. After transfection into acutely
      isolated newborn rat cortical neurons, homomeric mutant, but not heteromeric wild
      type/mutant channels, lowered the threshold of action potential firing and
      strongly increased cell excitability and firing frequency when compared with wild
      type channels. This is the first evidence in humans for a single-point,
      homozygous loss-of-function mutation in HCN2 potentially associated with
      generalized epilepsy with recessive inheritance.

PMID- 22131396
TI  - Dystrobrevin controls neurotransmitter release and muscle Ca(2+) transients by
      localizing BK channels in Caenorhabditis elegans.
AB  - Dystrobrevin is a major component of a dystrophin-associated protein complex. It
      is widely expressed in mammalian tissues, including the nervous system, in which
      it is localized to the presynaptic nerve terminal with unknown function. In a
      genetic screen for suppressors of a lethargic phenotype caused by a gain-of
      function isoform of SLO-1 in Caenorhabditis elegans, we isolated multiple loss-of
      function (lf) mutants of the dystrobrevin gene dyb-1.dyb-1(lf) phenocopied slo
      1(lf), causing increased neurotransmitter release at the neuromuscular junction,
      increased frequency of Ca(2+) transients in body-wall muscle, and abnormal
      locomotion behavior. Neuron- and muscle-specific rescue experiments suggest that
      DYB-1 is required for SLO-1 function in both neurons and muscle cells. DYB-1
      colocalized with SLO-1 at presynaptic sites in neurons and dense body regions in
      muscle cells, and dyb-1(lf) caused SLO-1 mislocalization in both types of cells
      without altering SLO-1 protein level. The neuronal phenotypes of dyb-1(lf) were
      partially rescued by mouse alpha-dystrobrevin-1. These observations revealed
      novel functions of the BK channel in regulating muscle Ca(2+) transients and of
      dystrobrevin in controlling neurotransmitter release and muscle Ca(2+) transients
      by localizing the BK channel.

PMID- 22131397
TI  - Reduced prefrontal connectivity in psychopathy.
AB  - Linking psychopathy to a specific brain abnormality could have significant
      clinical, legal, and scientific implications. Theories on the neurobiological
      basis of the disorder typically propose dysfunction in a circuit involving
      ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain
      imaging data to directly test whether psychopathy may indeed be associated with
      any structural or functional abnormality within this brain area. In this study,
      we employ two complementary imaging techniques to assess the structural and
      functional connectivity of vmPFC in psychopathic and non-psychopathic criminals.
      Using diffusion tensor imaging, we show that psychopathy is associated with
      reduced structural integrity in the right uncinate fasciculus, the primary white
      matter connection between vmPFC and anterior temporal lobe. Using functional
      magnetic resonance imaging, we show that psychopathy is associated with reduced
      functional connectivity between vmPFC and amygdala as well as between vmPFC and
      medial parietal cortex. Together, these data converge to implicate diminished
      vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

PMID- 22131398
TI  - MicroRNAs modulate Schwann cell response to nerve injury by reinforcing
      transcriptional silencing of dedifferentiation-related genes.
AB  - In the peripheral nervous system, Schwann cells (SCs) surrounding damaged axons
      undergo an injury response that is driven by an intricate transcriptional program
      and is critical for nerve regeneration. To examine whether these injury-induced
      changes in SCs are also regulated posttranscriptionally by miRNAs, we performed
      miRNA expression profiling of mouse sciatic nerve distal segment after crush
      injury. We also characterized the SC injury response in mice containing SCs with
      disrupted miRNA processing due to loss of Dicer. We identified 87 miRNAs that
      were expressed in mouse adult peripheral nerve, 48 of which were dynamically
      regulated after nerve injury. Most of these injury-regulated SC miRNAs were
      computationally predicted to inhibit drivers of SC
      dedifferentiation/proliferation and thereby re-enforce the transcriptional
      program driving SC remyelination. SCs deficient in miRNAs manifested a delay in
      the transition between the distinct differentiation states required to support
      peripheral nerve regeneration. Among the miRNAs expressed in adult mouse SCs, miR
      34a and miR-140 were identified as functional regulators of SC
      dedifferentiation/proliferation and remyelination, respectively. We found that
      miR-34a interacted with positive regulators of dedifferentiation and
      proliferation such as Notch1 and Ccnd1 to control cell cycle dynamics in SCs. miR
      140 targeted the transcription factor Egr2, a master regulator of myelination,
      and modulated myelination in DRG/SC cocultures. Together, these results
      demonstrate that SC miRNAs are important modulators of the SC regenerative
      response after nerve damage.

PMID- 22131399
TI  - Microglial Ca(2+)-activated K(+) channels are possible molecular targets for the
      analgesic effects of S-ketamine on neuropathic pain.
AB  - Ketamine is an important analgesia clinically used for both acute and chronic
      pain. The acute analgesic effects of ketamine are generally believed to be
      mediated by the inhibition of NMDA receptors in nociceptive neurons. However, the
      inhibition of neuronal NMDA receptors cannot fully account for its potent
      analgesic effects on chronic pain because there is a significant discrepancy
      between their potencies. The possible effect of ketamine on spinal microglia was
      first examined because hyperactivation of spinal microglia after nerve injury
      contributes to neuropathic pain. Optically pure S-ketamine preferentially
      suppressed the nerve injury-induced development of tactile allodynia and
      hyperactivation of spinal microglia. S-Ketamine also preferentially inhibited
      hyperactivation of cultured microglia after treatment with lipopolysaccharide,
      ATP, or lysophosphatidic acid. We next focused our attention on the Ca(2+)
      activated K(+) (K(Ca)) currents in microglia, which are known to induce their
      hyperactivation and migration. S-Ketamine suppressed both nerve injury-induced
      large-conductance K(Ca) (BK) currents and 1,3-dihydro-1-[2-hydroxy-5
      (trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS1619)
      induced BK currents in spinal microglia. Furthermore, the intrathecal
      administration of charybdotoxin, a K(Ca) channel blocker, significantly inhibited
      the nerve injury-induced tactile allodynia, the expression of P2X(4) receptors,
      and the synthesis of brain-derived neurotrophic factor in spinal microglia. In
      contrast, NS1619-induced tactile allodynia was completely inhibited by S
      ketamine. These observations strongly suggest that S-ketamine preferentially
      suppresses the nerve injury-induced hyperactivation and migration of spinal
      microglia through the blockade of BK channels. Therefore, the preferential
      inhibition of microglial BK channels in addition to neuronal NMDA receptors may
      account for the preferential and potent analgesic effects of S-ketamine on
      neuropathic pain.

PMID- 22131400
TI  - Heterosynaptic long-term potentiation at GABAergic synapses of spinal lamina I
      neurons.
AB  - Neurons in spinal dorsal horn lamina I play a pivotal role for nociception that
      critically depends on a proper balance between excitatory and inhibitory inputs.
      Any modification in synaptic strength may challenge this delicate balance. Long
      term potentiation (LTP) at glutamatergic synapses between nociceptive C-fibers
      and lamina I neurons is an intensively studied cellular model of pain
      amplification. In contrast, nothing is presently known about long-term changes of
      synaptic strength at inhibitory synapses in the spinal dorsal horn. Using a
      spinal cord-dorsal root slice preparation from rats, we show that conditioning
      stimulation of primary afferent fibers with a stimulating protocol that induces
      LTP at C-fiber synapses also triggered LTP at GABAergic synapses (LTP(GABA)).
      This LTP(GABA) was heterosynaptic in nature and was mediated by activation of
      group I metabotropic glutamate receptors. Opening of ionotropic glutamate
      receptor channels of the AMPA/KA or NMDA subtype was not required for LTP(GABA).
      Paired-pulse ratio, coefficient of variation, and miniature IPSCs analysis
      revealed that LTP(GABA) was expressed presynaptically. Nitric oxide as a
      retrograde messenger signal mediated this increase of GABA release at spinal
      inhibitory synapses. This novel form of synaptic plasticity in spinal nociceptive
      circuits may be an essential mechanism to maintain the relative balance between
      excitation and inhibition and to improve the signal-to-noise ratio in nociceptive
      pathways.

PMID- 22131401
TI  - A computational model for the influence of corollary discharge and proprioception
      on the perisaccadic mislocalization of briefly presented stimuli in complete
      darkness.
AB  - Spatial perception, the localization of stimuli in space, can rely on visual
      reference stimuli or on egocentric factors such as a stimulus position relative
      to eye gaze. In total darkness, only an egocentric reference frame provides
      sufficient information. When stimuli are briefly flashed around saccades, the
      localization error reveals potential mechanisms of updating such reference frames
      as described in several theories and computational models. Recent novel
      experimental evidence, however, showed that the maximum amount of mislocalization
      does not scale linearly with saccade amplitude but rather stays below 13 degrees 
      even for long saccades, which is different from predicted by present models. We
      propose a new model of perisaccadic mislocalization in complete darkness to
      account for this observation. According to this model, mislocalization arises not
      on the motor side by comparing a retinal position signal with an extraretinal eye
      position related signal but by updating stimulus position in visual areas through
      a combination of proprioceptive eye position and corollary discharge. Simulations
      with realistic input signals and temporal dynamics show that both signals
      together are used for spatial updating and in turn bring about perisaccadic
      mislocalization.

PMID- 22131402
TI  - Identifying specific light inputs for each subgroup of brain clock neurons in
      Drosophila larvae.
AB  - In Drosophila, opsin visual photopigments as well as blue-light-sensitive
      cryptochrome (CRY) contribute to the synchronization of circadian clocks. We
      focused on the relatively simple larval brain, with nine clock neurons per
      hemisphere: five lateral neurons (LNs), four of which express the pigment
      dispersing factor (PDF) neuropeptide, and two pairs of dorsal neurons (DN1s and
      DN2s). CRY is present only in the PDF-expressing LNs and the DN1s. The larval
      visual organ expresses only two rhodopsins (RH5 and RH6) and projects onto the
      LNs. We recently showed that PDF signaling is required for light to synchronize
      the CRY(-) larval DN2s. We now show that, in the absence of functional CRY,
      synchronization of the DN1s also requires PDF, suggesting that these neurons have
      no direct connection with the visual system. In contrast, the fifth (PDF(-)) LN
      does not require the PDF-expressing cells to receive visual system inputs. All
      clock neurons are light-entrained by light-dark cycles in the rh5(2);cry(b),
      rh6(1) cry(b), and rh5(2);rh6(1) double mutants, whereas the triple mutant is
      circadianly blind. Thus, any one of the three photosensitive molecules is
      sufficient, and there is no other light input for the larval clock. Finally, we
      show that constant activation of the visual system can suppress molecular
      oscillations in the four PDF-expressing LNs, whereas, in the adult, this effect
      of constant light requires CRY. A surprising diversity and specificity of light
      input combinations thus exists even for this simple clock network.

PMID- 22131403
TI  - An anxiolytic role for CRF receptor type 1 in the globus pallidus.
AB  - Corticotropin-releasing factor receptor type 1 (CRFR1) plays a major role in the
      regulation of neuroendocrine and behavioral responses to stress and is considered
      a key mediator of anxiety behavior. The globus pallidus external (GPe), a main
      relay center within the basal ganglia that is primarily associated with motor and
      associative functions, is one of the brain nuclei with the highest levels of
      CRFR1 expression in the rodent brain. However, the role of CRFR1 in the GPe is
      yet unknown. In the present study, we used a lentiviral-based system of RNA
      interference to show that knockdown of CRFR1 mRNA expression in the GPe of adult
      mice induces a significant increase in anxiety-like behavior, as revealed by the
      light-dark transfer, open-field, and elevated plus-maze tests. This effect was
      further confirmed by pharmacological administration of the selective CRFR1
      antagonist NBI 30775 (1.75 MUg/side) directly into the GPe. In the marble-burying
      test, blockade of CRFR1 in the GPe increased the percentage of marbles buried and
      the duration of burying behavior. Additionally, we present evidence suggesting
      that the enkephalin system is involved in the effect of GPe-CRFR1 on anxiety-like
      behavior. In contrast to the well established anxiogenic role of CRFR1 in the
      extended amygdala, our data reveal a novel anxiolytic role for CRFR1 in the GPe.

PMID- 22131404
TI  - SIRT1 modulates aggregation and toxicity through deacetylation of the androgen
      receptor in cell models of SBMA.
AB  - Posttranslational protein modifications can play a major role in disease
      pathogenesis; phosphorylation, sumoylation, and acetylation modulate the toxicity
      of a variety of proteotoxic proteins. The androgen receptor (AR) is substantially
      modified, in response to hormone binding, by phosphorylation, sumoylation, and
      acetylation; these modifications might thus contribute to DHT-dependent
      polyglutamine (polyQ)-expanded AR proteotoxicity in spinal and bulbar muscular
      atrophy (SBMA). SIRT1, a nuclear protein and deacetylase of the AR, is
      neuroprotective in many neurodegenerative disease models. Our studies reveal that
      SIRT1 also offers protection against polyQ-expanded AR by deacetylating the AR at
      lysines 630/632/633. This finding suggested that nuclear AR acetylation plays a
      role in the aberrant metabolism and toxicity of polyQ-expanded AR. Subsequent
      studies revealed that the polyQ-expanded AR is hyperacetylated and that
      pharmacologic reduction of acetylation reduces mutant AR aggregation. Moreover,
      genetic mutation to inhibit polyQ-expanded AR acetylation of lysines 630/632/633
      substantially decreased its aggregation and completely abrogated its toxicity in
      cell lines and motor neurons. Our studies also reveal one means by which the AR
      acetylation state likely modifies polyQ-expanded AR metabolism and toxicity,
      through its effect on DHT-dependent AR stabilization. Overall, our findings
      reveal a neuroprotective function of SIRT1 that operates through its
      deacetylation of polyQ-expanded AR and highlight the potential of both SIRT1 and
      AR acetylation as powerful therapeutic targets in SBMA.

PMID- 22131405
TI  - Morphologically distinct classes of relay cells exhibit regional preferences in
      the dorsal lateral geniculate nucleus of the mouse.
AB  - A fundamental feature of the mammalian visual system is the presence of separate
      channels that work in parallel to efficiently extract and analyze specific
      elements of a visual scene. Despite the extensive use of the mouse as a model
      system, it is not clear whether such parallel organization extends beyond the
      retina to subcortical structures, such as the dorsal lateral geniculate (dLGN) of
      thalamus. To begin to address this, we examined the morphology of biocytin-filled
      relay cells recorded in dLGN of mice. Based on a quantitative assessment of their
      dendritic architecture, we found that even at early postnatal ages relay cells
      could be readily classified as X-like (biconical), Y-like (symmetrical), or W
      like (hemispheric) and that each cell type was regionally specified in dLGN. X
      like cells were confined primarily to the monocular ventral region of dLGN. Y
      like cells occupied a central core that also contained ipsilateral eye
      projections, whereas W-like cells were found along the perimeter of dLGN. Similar
      to cat, Y-like cells were more prevalent than X- and W-like cells, and X-like
      cells tended to be smaller than other cell types. However, the dendritic fields
      of X- and W-like cells did not exhibit an orientation bias with respect to optic
      tract or boundaries of dLGN. Although we found clear morphological differences
      among relay cells, an analysis of their electrophysiological properties did not
      reveal any additional distinguishing characteristics. Overall, these data coupled
      with recent observations in the retina suggest that the mouse has many of the
      hallmark features of a system-wide parallel organization.

PMID- 22131406
TI  - Mechanism of accelerated current decay caused by an episodic ataxia type-1
      associated mutant in a potassium channel pore.
AB  - In Kv1.1, single point mutants found below the channel activation gate at residue
      V408 are associated with human episodic ataxia type-1, and impair channel
      function by accelerating decay of outward current during periods of membrane
      depolarization and channel opening. This decay is usually attributed to C-type
      inactivation, but here we provide evidence that this is not the case. Using
      voltage-clamp fluorimetry in Xenopus oocytes, and single-channel patch clamp in
      mouse ltk- cells, of the homologous Shaker channel (with the equivalent mutation
      V478A), we have determined that the mutation may cause current decay through a
      local effect at the activation gate, by destabilizing channel opening. We
      demonstrate that the effect of the mutant is similar to that of trapped 4
      aminopyridine in antagonizing channel opening, as the mutation and 10 mm 4-AP had
      similar, nonadditive effects on fluorescence recorded from the voltage-sensitive
      S4 helix. We propose a model where the Kv1.1 activation gate fails to enter a
      stabilized open conformation, from which the channel would normally C-type
      inactivate. Instead, the lower pore lining helix is able to enter an activated
      not-open conformation during depolarization. These results provide an
      understanding of the molecular etiology underlying episodic ataxia type-1 due to
      V408A, as well as biophysical insights into the links between the potassium
      channel activation gate, the voltage sensor and the selectivity filter.

PMID- 22131407
TI  - Dopaminergic modulation of risky decision-making.
AB  - Many psychiatric disorders are characterized by abnormal risky decision-making
      and dysregulated dopamine receptor expression. The current study was designed to
      determine how different dopamine receptor subtypes modulate risk-taking in young
      adult rats, using a "Risky Decision-making Task" that involves choices between
      small "safe" rewards and large "risky" rewards accompanied by adverse
      consequences. Rats showed considerable, stable individual differences in risk
      preference in the task, which were not related to multiple measures of reward
      motivation, anxiety, or pain sensitivity. Systemic activation of D2-like
      receptors robustly attenuated risk-taking, whereas drugs acting on D1-like
      receptors had no effect. Systemic amphetamine also reduced risk-taking, an effect
      which was attenuated by D2-like (but not D1-like) receptor blockade. Dopamine
      receptor mRNA expression was evaluated in a separate cohort of drug-naive rats
      characterized in the task. D1 mRNA expression in both nucleus accumbens shell and
      insular cortex was positively associated with risk-taking, while D2 mRNA
      expression in orbitofrontal and medial prefrontal cortex predicted risk
      preference in opposing nonlinear patterns. Additionally, lower levels of D2 mRNA
      in dorsal striatum were associated with greater risk-taking. These data strongly
      implicate dopamine signaling in prefrontal cortical-striatal circuitry in
      modulating decision-making processes involving integration of reward information
      with risks of adverse consequences.

PMID- 22131409
TI  - Getting drowsy? Alert/nonalert transitions and visual thalamocortical network
      dynamics.
AB  - The effects of different EEG brain states on spontaneous firing of cortical
      populations are not well understood. Such state shifts may occur frequently under
      natural conditions, and baseline firing patterns can impact neural coding (e.g.,
      signal-to-noise ratios, sparseness of coding). Here, we examine the effects of
      spontaneous transitions from alert to nonalert awake EEG states in the rabbit
      visual cortex (5 s before and after the state-shifts). In layer 4, we examined
      putative spiny neurons and fast-spike GABAergic interneurons; in layer 5, we
      examined corticotectal neurons. We also examined the behavior of retinotopically
      aligned dorsal lateral geniculate nucleus (LGNd) neurons, usually recorded
      simultaneously with the above cortical populations. Despite markedly reduced
      firing and sharply increased bursting in the LGNd neurons following the
      transition to the nonalert state, little change occurred in the spiny neurons of
      layer 4. However, fast-spike neurons of layer 4 showed a paradoxical increase in
      firing rates as thalamic drive decreased in the nonalert state, even though some
      of these cells received potent monosynaptic input from the same LGNd neurons
      whose rates were reduced. The firing rates of corticotectal neurons of layer 5,
      similarly to spiny cells of layer 4, were not state-dependent, but these cells
      did become more bursty in the nonalert state, as did the fast-spike cells. These
      results show that spontaneous firing rates of midlayer spiny populations are
      remarkably conserved following the shift from alert to nonalert states, despite
      marked reductions in excitatory thalamic drive and increased activity in local
      fast-spike inhibitory interneurons.

PMID- 22131408
TI  - Faster thalamocortical processing for dark than light visual targets.
AB  - ON and OFF visual pathways originate in the retina at the synapse between
      photoreceptor and bipolar cells. OFF bipolar cells are shorter in length and use
      receptors with faster kinetics than ON bipolar cells and, therefore, process
      information faster. Here, we demonstrate that this temporal advantage is
      maintained through thalamocortical processing, with OFF visual responses reaching
      cortex ~3-6 ms before ON visual responses. Faster OFF visual responses could be
      demonstrated in recordings from large populations of cat thalamic neurons
      representing the center of vision (both X and Y) and from subpopulations making
      connection with the same cortical orientation column. While the OFF temporal
      advantage diminished as visual responses reached their peak, the integral of the
      impulse response was greater in OFF than ON neurons. Given the stimulus
      preferences from OFF and ON channels, our results indicate that darks are
      processed faster than lights in the thalamocortical pathway.

PMID- 22131410
TI  - Neural correlates of trial-to-trial fluctuations in response caution.
AB  - Trial-to-trial variability in decision making can be caused by variability in
      information processing as well as by variability in response caution. In this
      paper, we study which neural components code for trial-to-trial adjustments in
      response caution using a new computational approach that quantifies response
      caution on a single-trial level. We found that the frontostriatal network updates
      the amount of response caution. In particular, when human participants were
      required to respond quickly, we found a positive correlation between trial-to
      trial fluctuations in response caution and the hemodynamic response in the
      presupplementary motor area and dorsal anterior cingulate. In contrast, on trials
      that required a change from a speeded response mode to a more accurate response
      mode or vice versa, we found a positive correlation between response caution and
      hemodynamic response in the anterior cingulate proper. These results indicate
      that for each decision, response caution is set through corticobasal ganglia
      functioning, but that individual choices differ according to the mechanisms that
      trigger changes in response caution.

PMID- 22131411
TI  - Influence of static eye and head position on tone-evoked gaze shifts.
AB  - The auditory system represents sound-source directions initially in head-centered
      coordinates. To program eye-head gaze shifts to sounds, the orientation of eyes
      and head should be incorporated to specify the target relative to the eyes. Here
      we test (1) whether this transformation involves a stage in which sounds are
      represented in a world- or a head-centered reference frame, and (2) whether
      acoustic spatial updating occurs at a topographically organized motor level
      representing gaze shifts, or within the tonotopically organized auditory system.
      Human listeners generated head-unrestrained gaze shifts from a large range of
      initial eye and head positions toward brief broadband sound bursts, and to tones
      at different center frequencies, presented in the midsagittal plane. Tones were
      heard at a fixed illusory elevation, regardless of their actual location, that
      depended in an idiosyncratic way on initial head and eye position, as well as on
      the tone's frequency. Gaze shifts to broadband sounds were accurate, fully
      incorporating initial eye and head positions. The results support the hypothesis
      that the auditory system represents sounds in a supramodal reference frame, and
      that signals about eye and head orientation are incorporated at a tonotopic
      stage.

PMID- 22131412
TI  - Ubiquitin homeostasis is critical for synaptic development and function.
AB  - The ubiquitin-proteasome system (UPS) controls protein abundance and is essential
      for many aspects of neuronal function. In ataxia (ax(J)) mice, profound
      neurological and synaptic defects result from a loss-of-function mutation in the
      proteasome-associated deubiquitinating enzyme Usp14, which is required for
      recycling ubiquitin from proteasomal substrates. Here, we show that transgenic
      complementation of ax(J) mice with neuronally expressed ubiquitin prevents early
      postnatal lethality, restores muscle mass, and corrects developmental and
      functional deficits resulting from the loss of Usp14, demonstrating that
      ubiquitin deficiency is a major cause of the neurological defects observed in the
      ax(J) mice. We also show that proteasome components are normally induced during
      the first 2 weeks of postnatal development, which coincides with dramatic
      alterations in polyubiquitin chain formation. These data demonstrate a critical
      role for ubiquitin homeostasis in synaptic development and function, and show
      that ubiquitin deficiency may contribute to diseases characterized by synaptic
      dysfunction.

PMID- 22131413
TI  - Higher-order interactions characterized in cortical activity.
AB  - In the cortex, the interactions among neurons give rise to transient coherent
      activity patterns that underlie perception, cognition, and action. Recently, it
      was actively debated whether the most basic interactions, i.e., the pairwise
      correlations between neurons or groups of neurons, suffice to explain those
      observed activity patterns. So far, the evidence reported is controversial.
      Importantly, the overall organization of neuronal interactions and the mechanisms
      underlying their generation, especially those of high-order interactions, have
      remained elusive. Here we show that higher-order interactions are required to
      properly account for cortical dynamics such as ongoing neuronal avalanches in the
      alert monkey and evoked visual responses in the anesthetized cat. A Gaussian
      interaction model that utilizes the observed pairwise correlations and event
      rates and that applies intrinsic thresholding identifies those higher-order
      interactions correctly, both in cortical local field potentials and spiking
      activities. This allows for accurate prediction of large neuronal population
      activities as required, e.g., in brain-machine interface paradigms. Our results
      demonstrate that higher-order interactions are inherent properties of cortical
      dynamics and suggest a simple solution to overcome the apparent formidable
      complexity previously thought to be intrinsic to those interactions.

PMID- 22131414
TI  - Chronic morphine treatment switches the effect of dopamine on excitatory synaptic
      transmission from inhibition to excitation in pyramidal cells of the basolateral
      amygdala.
AB  - Dopaminergic signaling in the basolateral amygdala (BLA) is important for drug
      stimulus learning that triggers relapse to drug-seeking behavior. However, little
      is known about adaptive changes in this signaling pathway upon chronic morphine
      treatment. In this paper, we observed the influence of chronic morphine treatment
      on the effect of dopamine (DA) on the excitatory transmission in the pyramidal
      cells of BLA in slices with the whole-cell patch-clamp method. We also studied
      its mechanism and significance with pharmacological approaches combined with
      biochemical and behavioral techniques. The results showed that chronic morphine
      exposure switched the effect of DA on the excitatory synaptic transmission from
      inhibition to excitation; the chronic morphine-induced switching action on the
      effect of DA was due to its influence on D1 receptors; the site of the effect of
      chronic morphine treatment on D1 receptors was at presynaptic locus; chronic
      morphine treatment induced a significant increase in the amount of D1 receptor
      expression in the synaptosomes and synaptosomal membrane fraction from BLA; the
      enhancement of presynaptic glutamate release by D1 receptor agonist upon chronic
      morphine treatment was dependent on the activation of cAMP-dependent protein
      kinase; and the intra-BLA injection of D1 receptor antagonist canceled the
      conditioned place aversion (CPA) in morphine-dependent rats. In conclusion,
      chronic morphine treatment switches the effect of DA on the excitatory synaptic
      transmission from inhibition to excitation by the presynaptic D1 receptor amount
      increase-mediated glutamate release in the pyramidal cells of BLA and the
      blockade of D1 receptors in BLA cancels CPA in morphine-dependent rats.

PMID- 22131415
TI  - Synaptic stimulation of mTOR is mediated by Wnt signaling and regulation of
      glycogen synthetase kinase-3.
AB  - The persistent or "late" phase of long-term potentiation (L-LTP), which requires
      protein synthesis, can be induced by relatively intense synaptic activity. The
      ability of such strong synaptic protocols to engage the translational machinery
      and produce plasticity-related proteins, while weaker protocols activate only
      posttranslational processes and transient potentiation (early LTP; E-LTP), is not
      understood. Among the major translation control pathways in neurons, the
      stimulation of mammalian target of rapamycin (mTOR) is a key event in the
      induction of L-LTP. We report that mTOR is tonically suppressed in rat
      hippocampus under resting conditions, a consequence of the basal activity of
      glycogen synthetase kinase 3 (GSK3). This suppression could be overcome by weak
      synaptic stimulation in the presence of the beta-adrenergic agonist
      isoproterenol, a combination that induced L-LTP, and activation of mTOR coincided
      with the Akt-mediated phosphorylation of GSK3. Surprisingly, while isoproterenol
      alone elevated Akt activity, it failed to increase GSK3 phosphorylation or mTOR
      signaling, showing that Akt was uncoupled from these effectors in the absence of
      synaptic stimulation. With the addition of weak stimulation, Akt signaled to GSK3
      and mTOR, a gating effect that was mediated by voltage-dependent Ca(2+) channels
      and the Wnt pathway. mTOR could be stimulated by pharmacological inhibition,
      enabling weak HFS to induce L-LTP. These results establish GSK3 as an integrator
      of Akt and Wnt signals and suggest that overcoming GSK3-mediated suppression of
      mTOR is a key event in the induction of L-LTP by synaptic activity.

PMID- 22131416
TI  - Event-related repetitive transcranial magnetic stimulation of posterior superior
      temporal sulcus improves the detection of threatening postural changes in human
      bodies.
AB  - Perceiving others' emotions through their body movements and postures is crucial
      for successful social interaction. While imaging studies indicate that perceiving
      body emotions relies upon a wide network of subcortico-cortical neural regions,
      little is known on the causative role of different nodes of this network. We
      applied event-related repetitive transcranial magnetic stimulation (rTMS) over
      nonfacial, body- and action-related extrastriate (EBA), temporal (pSTS), and
      premotor (vPM) cortices to test their active contribution in perceiving changes
      between two successive images of either threatening or neutral human body or
      animal postures. While stimulation of EBA and vPM showed no selective effect on
      threatening stimuli with respect to neutral ones, rTMS over pSTS selectively
      impaired neutral posture detection and increased the accuracy in detecting
      changes of threatening human postures with respect to all other experimental
      conditions. No such effect was found for animal stimuli. These results support
      the notion that pSTS is crucially devoted to the detection of socially relevant
      information concerning others' actions, fostering the notion that amygdalo
      temporo-cortical modulatory connections mediate perception of emotionally salient
      body postures.

PMID- 22131417
TI  - Patterns of presynaptic activity and synaptic strength interact to produce motor
      output.
AB  - Motor neuron activity is coordinated by premotor networks into a functional motor
      pattern by complex patterns of synaptic drive. These patterns combine both the
      temporal pattern of spikes of the premotor network and the profiles of synaptic
      strengths (i.e., conductances). Given the complexity of premotor networks in
      vertebrates, it has been difficult to ascertain the relative contributions of
      temporal patterns and synaptic strength profiles to the motor patterns observed
      in these animals. Here, we use the leech (Hirudo sp.) heartbeat central pattern
      generator (CPG), in which we can measure both the temporal pattern and the
      synaptic strength profiles of the entire premotor network and the motor outflow
      in individual animals. In this system, a series of motor neurons all receive
      input from the same premotor interneurons of the CPG but must be coordinated
      differentially to produce a functional pattern. These properties allow a
      theoretical and experimental dissection of the rules that govern how temporal
      patterns and synaptic strength profiles are combined in motor neurons so that
      functional motor patterns emerge, including an analysis of the impact of animal
      to-animal variation in input to such variation in output. In the leech, segmental
      heart motor neurons are coordinated alternately in a synchronous and peristaltic
      pattern. We show that synchronous motor patterns result from a nearly synchronous
      premotor temporal pattern produced by the leech heartbeat CPG. For peristaltic
      motor patterns, the staggered premotor temporal pattern determines the phase
      range over which segmental motor neurons can fire while synaptic strength
      profiles define the intersegmental motor phase progression realized.

PMID- 22131418
TI  - Parietal cortex and insula relate to evidence seeking relevant to reward-related
      decisions.
AB  - Decisions are most effective after collecting sufficient evidence to accurately
      predict rewarding outcomes. We investigated whether human participants optimally
      seek evidence and we characterized the brain areas associated with their evidence
      seeking. Participants viewed sequences of bead colors drawn from hidden urns and
      attempted to infer the majority bead color in each urn. When viewing each bead
      color, participants chose either to seek more evidence about the urn by drawing
      another bead (draw choices) or to infer the urn contents (urn choices). We then
      compared their evidence seeking against that predicted by a Bayesian ideal
      observer model. By this standard, participants sampled less evidence than
      optimal. Also, when faced with urns that had bead color splits closer to chance
      (60/40 versus 80/20) or potential monetary losses, participants increased their
      evidence seeking, but they showed less increase than predicted by the ideal
      observer model. Functional magnetic resonance imaging showed that urn choices
      evoked larger hemodynamic responses than draw choices in the insula, striatum,
      anterior cingulate, and parietal cortex. These parietal responses were greater
      for participants who sought more evidence on average and for participants who
      increased more their evidence seeking when draws came from 60/40 urns. The
      parietal cortex and insula were associated with potential monetary loss. Insula
      responses also showed modulation with estimates of the expected gains of urn
      choices. Our findings show that participants sought less evidence than predicted
      by an ideal observer model and their evidence-seeking behavior may relate to
      responses in the insula and parietal cortex.

PMID- 22131420
TI  - Syntaxin1A lateral diffusion reveals transient and local SNARE interactions.
AB  - At the synapse, vesicles stably dock at the active zone. However, in cellular
      membranes, proteins undergo a diffusive motion. It is not known how the motion of
      membrane proteins involved in vesicle exocytosis is compatible with both vesicle
      docking and the dynamic remodeling of the plasma membrane imposed by cycles of
      exocytosis and endocytosis. To address this question, we studied the motion of
      the presynaptic membrane protein syntaxin1A at both the population and single
      molecule levels in primary cultures of rat spinal cord neurons. Syntaxin1A was
      rapidly exchanged between synaptic and extrasynaptic regions. Changes in
      syntaxin1A mobility were associated with interactions related to the formation of
      the exocytotic complex. Finally, we propose a reaction-diffusion model
      reconciling the observed diffusive properties of syntaxin at the population level
      and at the molecular level. This work allows us to describe the diffusive
      behavior and kinetics of interactions between syntaxin1A and its partners that
      lead to its transient stabilization at the synapse.

PMID- 22131419
TI  - Membrane-initiated estradiol signaling induces spinogenesis required for female
      sexual receptivity.
AB  - Estrogens have profound actions on the structure of the nervous system during
      development and in adulthood. One of the signature actions of estradiol is to
      alter the morphology of neural processes. In the hippocampus, estradiol modulates
      spines and cellular excitability that affect cognitive behaviors. In the
      hypothalamus, estradiol increases spine density in mediobasal hypothalamic nuclei
      that regulate reproduction. The hypothalamic arcuate nucleus (ARH), an important
      site for modulation of female sexual receptivity, has a sexual dimorphism in
      dendritic spine density that favors females. In the present study, we used both
      beta-actin immunostaining and Golgi staining to visualize estradiol-induced
      changes in spine density in Long-Evans rats. Golgi impregnation was used to
      visualize spine shape, and then beta-actin immunoreactivity was used as a
      semiquantitative measure of spine plasticity since actin forms the core of
      dendritic spines. At 4 h after estradiol treatment, both beta-actin
      immunofluorescence and filopodial spines were increased (from 70.57 +/- 1.09% to
      78.01 +/- 1.05%, p < 0.05). Disruption of estradiol-induced beta-actin
      polymerization with cytochalasin D attenuated lordosis behavior, indicating the
      importance of estradiol-mediated spinogenesis for female sexual receptivity
      (81.43 +/- 7.05 to 35.00 +/- 11.76, p < 0.05). Deactivation of cofilin, an actin
      depolymerizing factor is required for spinogenesis. Membrane-initiated estradiol
      signaling involving the metabotropic glutamate receptor 1a was responsible for
      the phosphorylation and thereby deactivation of cofilin. These data demonstrate
      that estradiol-induced spinogenesis in the ARH is an important cellular mechanism
      for the regulation of female sexual behavior.

PMID- 22131421
TI  - Perceptual constancy of texture roughness in the tactile system.
AB  - Our tactual perception of roughness is independent of the manner in which we
      touch the surface. A brick surface feels rough no matter how slowly or how
      rapidly we move our fingers, despite the fluctuating sensory inputs that are
      transmitted to the finger. Current theories of roughness perception rely solely
      on inputs from the cutaneous afferents, which are highly affected by scan
      velocity and force. The question then is: how is roughness constancy achieved? To
      this end, we characterized the subject's perceived roughness in six scanning
      conditions. These included two modes of touch: direct touch, where the finger is
      in contact with the surface, and indirect touch, where the surface is scanned
      with a hand-held probe; and three scanning modes: active (moving the hand across
      a stationary surface), passive (moving the surface across a stationary hand), and
      pseudo-passive (subject's hand is moved by the experimenter across a stationary
      surface). Here, we show that roughness constancy is preserved during active but
      not passive scanning, indicating that the hand movement is necessary for
      roughness constancy in both direct and indirect touch. Roughness constancy is
      also preserved during pseudo-passive scanning, which stresses the importance of
      proprioceptive input. The results show that cutaneous input provides the signals
      necessary for roughness perception and that proprioceptive input resulting from
      hand movement-rather than a motor efference copy-is necessary to achieve
      roughness constancy. These findings have important implications in providing
      realistic sensory feedback for prosthetic-hand users.

PMID- 22131422
TI  - CCAAT/enhancer binding protein-delta expression by dendritic cells regulates CNS
      autoimmune inflammatory disease.
AB  - CCAAT enhancer binding protein-delta (C/EBPdelta) is a transcription factor that
      regulates inflammatory processes mediating bystander neuronal injury and CNS
      autoimmune inflammatory disease. The mechanism of the involvement of C/EBPdelta
      in these processes remains to be determined. Here, we examined the cellular
      source(s) and mechanisms by which C/EBPdelta may be involved in an animal model
      of multiple sclerosis. Mice deficient in C/EBPdelta expression exhibited less
      severe clinical disease than wild-type littermates in response to induction of
      experimental autoimmune encephalomyelitis (EAE) by vaccination with a myelin
      oligodendrocyte glycoprotein (MOG) fragment. This reduction in EAE severity was
      associated with a significant alteration in the complement of major CNS T-helper
      (Th) cell subtypes throughout disease, manifest as reduced ratios of Th17 cells
      to regulatory T-cells (Tregs). Studies in bone marrow chimeric mice indicated
      that C/EBPdelta expression by peripherally derived immune cells mediates
      C/EBPdelta involvement in EAE. Follow up in vitro and in vivo examination of
      dendritic cell (DC) mediated Th-cell development suggests that C/EBPdelta
      suppresses DC expression of interleukin-10 (IL-10), favoring Th17 over Treg
      development. In vitro and in vivo blockade of IL-10 signaling attenuated the
      effect of reduced C/EBPdelta expression by DCs on Th17:Treg ratios. These
      findings identify C/EBPdelta as an important DC transcription factor in CNS
      autoimmune inflammatory disease by virtue of its capacity to alter the Th17:Treg
      balance in an IL-10 dependent fashion.

PMID- 22131423
TI  - Attentional modulation of neuromagnetic evoked responses in early human visual
      cortex and parietal lobe following a rank-order rule.
AB  - Top-down voluntary attention modulates the amplitude of magnetic evoked fields in
      the human visual cortex. Whether such modulation is flexible enough to adapt to
      the demands of complex tasks in which abstract rules must be applied to select a
      target in the presence of distracters remains unclear. We recorded brain
      neuromagnetic activity using whole-head magnetoencephalography in 14 human
      subjects during a rule-guided target selection task, and applied event-related
      Synthetic Aperture Magnetometry to image instantaneous changes in neuromagnetic
      source activity throughout the brain. During the task subjects selected one of
      two stimuli (the target) and ignored the other (the distracter) based on a color
      rank rule (color 1 > color 2 > color 3). Our results revealed that in early
      visual color-sensitive areas and the parietal cortex visual stimuli evoke
      activity that scaled following the rank-order rule. This effect was stronger and
      occurred later in the parietal lobe (~200 ms after target/distracter onset)
      relative to early visual areas (~180 ms). Moreover, we found that transient
      changes in the target's motion direction evoked stronger responses relative to
      similar changes in the distracter at ~180 ms from change onset in contralateral
      areas hMT+/V5. These results suggest that during target selection and allocation
      of attention to a stimulus, top-down signals adjust their intensity following
      complex selection rules according to the organism's priorities, thereby
      differentially modulating neuromagnetic activity across visual cortical areas.

PMID- 22131424
TI  - Alterations in intrinsic membrane properties and the axon initial segment in a
      mouse model of Angelman syndrome.
AB  - The axon initial segment (AIS) is the site of action potential initiation in
      neurons. Recent studies have demonstrated activity-dependent regulation of the
      AIS, including homeostatic changes in AIS length, membrane excitability, and the
      localization of voltage-gated Na(+) channels. The neurodevelopmental disorder
      Angelman syndrome (AS) is usually caused by the deletion of small portions of the
      maternal copy of chromosome 15, which includes the UBE3A gene. A mouse model of
      AS has been generated and these mice exhibit multiple neurological abnormalities
      similar to those observed in humans. We examined intrinsic properties of
      pyramidal neurons in hippocampal area CA1 from AS model mice and observed
      alterations in resting membrane potential, threshold potential, and action
      potential amplitude. The altered intrinsic properties in the AS mice were
      correlated with significant increases in the expression of the alpha1 subunit of
      Na/K-ATPase (alpha1-NaKA), the Na(+) channel NaV1.6, and the AIS anchoring
      protein ankyrin-G, as well as an increase in length of the AIS. These findings
      are the first evidence for pathology of intrinsic membrane properties and AIS
      specific changes in AS, a neurodevelopmental disorder associated with autism.

PMID- 22131425
TI  - Striatal dysfunctions associated with mitochondrial DNA damage in dopaminergic
      neurons in a mouse model of Parkinson's disease.
AB  - Parkinson's disease (PD) is one of the most common progressive neurodegenerative
      disorders, characterized by resting tremor, rigidity, bradykinesia, and postural
      instability. These symptoms are associated with massive loss of tyrosine
      hydroxylase-positive neurons in the substantia nigra (SN) causing an estimated 70
      80% depletion of dopamine (DA) in the striatum, where their projections are
      located. Although the etiology of PD is unknown, mitochondrial dysfunctions have
      been associated with the disease pathophysiology. We used a mouse model
      expressing a mitochondria-targeted restriction enzyme, PstI or mito-PstI, to
      damage mitochondrial DNA (mtDNA) in dopaminergic neurons. The expression of mito
      PstI induces double-strand breaks in the mtDNA, leading to an oxidative
      phosphorylation deficiency, mostly due to mtDNA depletion. Taking advantage of a
      dopamine transporter (DAT) promoter-driven tetracycline transactivator protein
      (tTA), we expressed mito-PstI exclusively in dopaminergic neurons, creating a
      novel PD transgenic mouse model (PD-mito-PstI mouse). These mice recapitulate
      most of the major features of PD: they have a motor phenotype that is reversible
      with l-DOPA treatment, a progressive neurodegeneration of the SN dopaminergic
      population, and striatal DA depletion. Our results also showed that behavioral
      phenotypes in PD-mito-PstI mice were associated with striatal dysfunctions
      preceding SN loss of tyrosine hydroxylase-positive neurons and that other
      neurotransmitter systems [noradrenaline (NE) and serotonin (5-HT)] were increased
      after the disruption of DA neurons, potentially as a compensatory mechanism. This
      transgenic mouse model provides a novel model to study the role of mitochondrial
      defects in the axonal projections of the striatum in the pathophysiology of PD.

PMID- 22131426
TI  - Visual pathway for the optokinetic reflex in infant macaque monkeys.
AB  - The horizontal optokinetic nystagmus (hOKN) in primates is immature at birth. To
      elucidate the early functional state of the visual pathway for hOKN, retinal slip
      neurons were recorded in the nucleus of the optic tract and dorsal terminal
      nucleus (NOT-DTN) of 4 anesthetized infant macaques. These neurons were direction
      selective for ipsiversive stimulus movement shortly after birth [postnatal day 9
      (P9)], although at a lower direction selectivity index (DSI). The DSI in the
      older infants (P12, P14, P60) was not different from adults. A total of 96% of
      NOT-DTN neurons in P9, P12, and P14 were binocular, however, significantly more
      often dominated by the contralateral eye than in adults. Already in the youngest
      animals, NOT-DTN neurons were well tuned to different stimulus velocities;
      however, tuning was truncated toward lower stimulus velocities when compared with
      adults. As early as at P12, electrical stimulation in V1 elicited orthodromic
      responses in the NOT-DTN. However, the incidence of activated neurons was much
      lower in infants (40-60% of the tested NOT-DTN neurons) than in adults (97%).
      Orthodromic latencies from V1 were significantly longer in P12-P14 (x = 12.2 +/-
      8.9 ms) than in adults (x = 3.51 +/- 0.81 ms). At the same age, electrical
      stimulation in motion-sensitive area MT was more efficient in activating NOT-DTN
      neurons (80% of the tested cells) and yielded shorter latencies than in V1 (x =
      7.8 +/- 3.02 ms; adult x = 2.99 +/- 0.85 ms). The differences in discharge rate
      between neurons in the NOT-DTN contra- and ipsilateral to the stimulated eye are
      equivalent to the gain asymmetry between monocularly elicited OKN in temporonasal
      and nasotemporal direction at the various ages.

PMID- 22131427
TI  - Noninvasive associative plasticity induction in a corticocortical pathway of the
      human brain.
AB  - Coincident pairing of presynaptic and postsynaptic activity selectively
      strengthens synaptic connections, a key mechanism underlying cortical plasticity.
      Using paired associative transcranial magnetic stimulation (TMS), we demonstrate
      selective potentiation of physiological connectivity between two human brain
      regions, ventral premotor cortex (PMv) and primary motor cortex (M1) after
      repeated paired-pulse TMS of PMv and M1. The effect was anatomically specific:
      paired stimulation of the presupplementary motor area and M1 did not induce
      changes in PMv-M1 pathway connectivity. The effect was dependent on stimulation
      order: repeated stimulation of PMv before M1 led to strengthening of the PMv-M1
      pathway, while repeated stimulation of M1 before PMv diminished the strength of
      the PMv-M1 pathway. The expression of the change in the pathway depended on the
      cognitive state of the subject at the time of testing: when the subject was
      tested at rest, paired PMv-M1 stimulation led to an increased inhibitory
      influence of PMv over M1, but when the subject was tested while engaged in a
      visuomotor task, PMv-M1 stimulation led to an increased facilitatory influence of
      PMv over M1. Plasticity evolved rapidly, lasted for at least 1 h, and began to
      reverse 3 h after intervention.

PMID- 22131428
TI  - Hippocampal hyperactivation associated with cortical thinning in Alzheimer's
      disease signature regions in non-demented elderly adults.
AB  - Alzheimer's disease (AD) is associated with functional and structural alterations
      in a distributed network of brain regions supporting memory and other cognitive
      domains. Functional abnormalities are present in mild cognitive impairment (MCI)
      with evidence of early hyperactivity in medial temporal lobe regions, followed by
      failure of hippocampal activation as dementia develops. Atrophy in a consistent
      set of cortical regions, the "cortical signature of AD," has been reported at the
      stage of dementia, MCI, and even in clinically normal (CN) older individuals
      predicted to develop AD. Despite multiple lines of evidence for each of these
      findings, the relationship between this structural marker of AD-related
      neurodegeneration and this functional marker of the integrity of the episodic
      memory system has not yet been elucidated. We investigated this relationship in
      34 nondemented older humans (CN, N = 18; MCI, N = 16). Consistent with previous
      studies, we found evidence of hippocampal hyperactivation in MCI compared with
      CN. Additionally, within this MCI group, increased hippocampal activation
      correlated with cortical thinning in AD-signature regions. Even within the CN
      group, increased hippocampal activity was negatively correlated with cortical
      thinning in a subset of regions, including the superior parietal lobule (r = 
      0.66; p < 0.01). These findings, across a continuum of nondemented and mildly
      impaired older adults, support the hypothesis that paradoxically increased
      hippocampal activity may be an early indicator of AD-related neurodegeneration in
      a distributed network.

PMID- 22131429
TI  - Highwire regulates guidance of sister axons in the Drosophila mushroom body.
AB  - Axons often form synaptic contacts with multiple targets by extending branches
      along different paths. PHR (Pam/Highwire/RPM-1) family ubiquitin ligases are
      important regulators of axon development, with roles in axon outgrowth, target
      selection, and synapse formation. Here we report the function of Highwire, the
      Drosophila member of the PHR family, in promoting the segregation of sister axons
      during mushroom body (MB) formation. Loss of highwire results in abnormal
      development of the axonal lobes in the MB, leading to thinned and shortened
      lobes. The highwire defect is attributable to guidance errors after axon
      branching, in which sister axons that should target different lobes instead
      extend together into the same lobe. The highwire mutant MB displays elevation in
      the level of the MAPKKK Wallenda/DLK (dual leucine zipper kinase), a previously
      identified substrate of Highwire, and genetic suppression studies show that
      Wallenda/DLK is required for the highwire MB phenotype. The highwire lobe defect
      is limited to alpha/beta lobe axons, but transgenic expression of highwire in the
      pioneering alpha'/beta' neurons rescues the phenotype. Mosaic analysis further
      shows that alpha/beta axons of highwire mutant clones develop normally,
      demonstrating a non-cell-autonomous role of Highwire for axon guidance. Genetic
      interaction studies suggest that Highwire and Plexin A signals may interact to
      regulate normal morphogenesis of alpha/beta axons.

PMID- 22131430
TI  - Homeostatic strengthening of inhibitory synapses is mediated by the accumulation
      of GABA(A) receptors.
AB  - Mechanisms of homeostatic plasticity scale synaptic strength according to changes
      in overall activity to maintain stability in neuronal network function. This
      study investigated mechanisms of GABAergic homeostatic plasticity. Cultured
      neurons exposed to depolarizing conditions reacted with an increased firing rate
      (high activity, HA) that normalized to control levels after 48 h of treatment. HA
      treated hippocampal neurons displayed an attenuated response to further changes
      in depolarization, and the firing rate in HA-treated neurons increased above
      normalized levels when inhibition was partially reduced back to the level of
      control neurons. The amplitude and frequency of mIPSCs in hippocampal neurons
      increased after 48 h of HA, and increases in the size of GABA(A) receptor gamma2
      subunit clusters and presynaptic GAD-65 puncta were observed. Investigation of
      the time course of inhibitory homeostasis suggested that accumulation of GABA(A)
      receptors preceded presynaptic increases in GAD-65 puncta size. Interestingly,
      the size of GABA(A) receptor gamma2 subunit clusters that colocalized with GAD-65
      were larger at 12 h, coinciding in time with the increase found in mIPSC
      amplitude. The rate of internalization of GABA(A) receptors, a process involved
      in regulating the surface expression of inhibitory receptors, was slower in HA
      treated neurons. These data also suggest that increased receptor expression was
      consolidated with presynaptic changes. HA induced an increase in postsynaptic
      GABA(A) receptors through a decrease in the rate of internalization, leading to
      larger synaptically localized receptor clusters that increased GABAergic synaptic
      strength and contributed to the homeostatic stabilization of neuronal firing
      rate.

PMID- 22131431
TI  - Perceiving the tree in the woods: segregating brain responses to stimuli
      constituting natural scenes.
AB  - Conventional neuroscientific methods are inadequate for separating the brain
      responses related to the simultaneous processing of different parts of a natural
      scene. In the present human electroencephalogram (EEG) study, we overcame this
      limitation by tagging concurrently presented backgrounds and objects with
      different presentation frequencies. As a result, background and object elicited
      different steady-state visual evoked potentials (SSVEPs), which were separately
      quantified in the frequency domain. We analyzed the effects of semantic
      consistency and inconsistency between background and object on SSVEP amplitudes,
      topography, and tomography [variable resolution electromagnetic tomography
      (VARETA)]. The results revealed that SSVEPs related to background processing
      showed higher amplitudes in the consistent as opposed to the inconsistent
      condition, whereas object-related SSVEPs showed the reversed pattern of effects.
      Given the SSVEPs' sensitivity to visual attention, the results indicate that
      semantic inconsistency leads to greater attention focused on the object. If all
      image parts are semantically related, attention is rather directed to the
      background. The attentional advantage to inconsistent objects in a scene is
      likely the result of a mismatch between background-based expectations and
      semantic object information. A clear lateralization of the consistency effect in
      the anterior temporal lobes indicates functional hemispheric asymmetries in
      processing background- and object-related semantic information. In summary, the
      present study is the first to demonstrate the feasibility of SSVEPs to unravel
      the respective contributions of concurrent neuronal processes involved in the
      perception of background and object.

PMID- 22131432
TI  - On the dynamic nature of the engram: evidence for circuit-level reorganization of
      object memory traces following reactivation.
AB  - Research has implicated the perirhinal cortex (PRh) in several aspects of object
      recognition memory. The specific role of the hippocampus (HPC) remains
      controversial, but its involvement in object recognition may pertain to
      processing contextual information in relation to objects rather than object
      representation per se. Here we investigated the roles of the PRh and HPC in
      object memory reconsolidation using the spontaneous object recognition task for
      rats. Intra-PRh infusions of the protein synthesis inhibitor anisomycin
      immediately following memory reactivation prevented object memory
      reconsolidation. Similar deficits were observed when a novel object or a salient
      contextual change was introduced during the reactivation phase. Intra-HPC
      infusions of anisomycin, however, blocked object memory reconsolidation only when
      a contextual change was introduced during reactivation. Moreover, disrupting
      functional interaction between the HPC and PRh by infusing anisomycin
      unilaterally into each structure in opposite hemispheres also impaired
      reconsolidation when reactivation was done in an altered context. These results
      show for the first time that the PRh is critical for reconsolidation of object
      memory traces and provide insight into the dynamic process of object memory
      storage; the selective requirement for hippocampal involvement following
      reactivation in an altered context suggests a substantial circuit level object
      trace reorganization whereby an initially PRh-dependent object memory becomes
      reliant on both the HPC and PRh and their interaction. Such trace reorganization
      may play a central role in reconsolidation-mediated memory updating and could
      represent an important aspect of lingering consolidation processes proposed to
      underlie long-term memory modulation and stabilization.

PMID- 22131433
TI  - Opioid-sensitive GABA inputs from rostromedial tegmental nucleus synapse onto
      midbrain dopamine neurons.
AB  - Opioids increase dopamine release in the brain through inhibition of GABA-A IPSCs
      onto dopamine cells. Immunolabeling indicates that GABA neurons in the
      rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral
      tegmental area, send a dense projection to midbrain dopamine neurons stain for MU
      opioid receptors. There is however, little functional evidence that these neurons
      play a role in the opioid-dependent increase in dopamine neuron activity. The
      present study used retrograde tracers injected into the ventral tegmental area
      and substantia nigra (VTA/SN) to identify RMTg neurons that project to the
      VTA/SN. Whole-cell current-clamp and cell-attached recordings from labeled RMTg
      neurons were performed in sagittal slices from rat. The rhythmic spontaneous
      firing rate of RMTg neurons was decreased and the membrane potential was
      hyperpolarized in response to application of MU-opioid agonist DAMGO. Agonists
      that act at kappa- and delta-opioid receptors (U69593 and DPDPE) failed to
      hyperpolarize RMTg neurons. Whole-cell recordings made in dopamine neurons
      revealed rhythmic, large amplitude spontaneous IPSCs that had a similar
      frequency, pattern and opioid sensitivity to the firing of RMTg neurons. In
      addition, electrical and channelrhodopsin-2 stimulation within the RMTg evoked
      GABA-A IPSCs in dopamine neurons that were inhibited by MU-opioid agonists DAMGO,
      but not kappa- and delta-opioid agonists. Thus, this study demonstrates
      functional connection from the RMTg to the VTA/SN mediated by a dense, opioid
      sensitive GABA innervation, and that the RMTg is a key structure in the MU-opioid
      receptor-dependent regulation of dopamine neurons.

PMID- 22131435
TI  - Direct puncture of the highest cervical segment of the internal carotid artery
      for treatment of an iatrogenic carotid cavernous fistula in a patient with Ehlers
      Danlos syndrome.
AB  - A case of an iatrogenic direct carotid cavernous fistula in a patient with a
      history of Ehlers-Danlos syndrome and multiple aneurysms is reported. The fistula
      developed after unsuccessful surgical thrombectomy and revision of an occluded
      interposition graft inserted to treat a right internal carotid artery aneurysm.
      Direct puncture of the right internal carotid artery at the level of the skull
      base was performed to close the fistula. This case shows that direct puncture at
      the highest cervical segment of the internal carotid artery is another option for
      treatment of a direct carotid cavernous fistula when a standard transarterial or
      transvenous approach is not feasible.

PMID- 22131434
TI  - Congenital CNS hypomyelination in the Fig4 null mouse is rescued by neuronal
      expression of the PI(3,5)P(2) phosphatase Fig4.
AB  - The plt (pale tremor) mouse carries a null mutation in the Fig4(Sac3) gene that
      results in tremor, hypopigmentation, spongiform degeneration of the brain, and
      juvenile lethality. FIG4 is a ubiquitously expressed phosphatidylinositol 3,5
      bisphosphate phosphatase that regulates intracellular vesicle trafficking along
      the endosomal-lysosomal pathway. In humans, the missense mutation FIG4(I41T)
      combined with a FIG4 null allele causes Charcot-Marie-Tooth 4J disease, a severe
      form of peripheral neuropathy. Here we show that Fig4 null mice exhibit a
      dramatic reduction of myelin in the brain and spinal cord. In the optic nerve,
      smaller-caliber axons lack myelin sheaths entirely, whereas many large- and
      intermediate-caliber axons are myelinated but show structural defects at nodes of
      Ranvier, leading to delayed propagation of action potentials. In the Fig4 null
      brain and optic nerve, oligodendrocyte (OL) progenitor cells are present at
      normal abundance and distribution, but the number of myelinating OLs is greatly
      compromised. The total number of axons in the Fig4 null optic nerve is not
      reduced. Developmental studies reveal incomplete myelination rather than elevated
      cell death in the OL linage. Strikingly, there is rescue of CNS myelination and
      tremor in transgenic mice with neuron-specific expression of Fig4, demonstrating
      a non-cell-autonomous function of Fig4 in OL maturation and myelin development.
      In transgenic mice with global overexpression of the human pathogenic FIG4
      variant I41T, there is rescue of the myelination defect, suggesting that the CNS
      of CMT4J patients may be protected from myelin deficiency by expression of the
      FIG4(I41T) mutant protein.

PMID- 22131436
TI  - Factors associated with rapid neurological improvement 24 h following intra
      arterial thrombolytic treatment for acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Significant 24 h improvement is the strongest indicator
      of functional recovery following thrombolytic treatment for acute ischemic
      stroke. This study sought to analyze factors contributing to rapid neurological
      improvement (RNI) following intra-arterial thrombolytic treatment (IATT).
      METHODS: Angiograms and clinical information derived from consecutive patients
      receiving treatment initiated within 6 h of stroke onset were retrospectively
      reviewed. RNI was defined as at least 50% 24 h improvement on the National
      Institutes of Health Stroke Scale score. Logistic regression analysis identified
      factors associated with RNI. Variables tested included: age, gender, serum
      glucose, platelet count, pial collateral formation, presenting National
      Institutes of Health Stroke Scale score, time to treatment, extent of
      reperfusion, site and location of occlusion, treatment agent and systolic blood
      pressure. RESULTS: Greater than 50% reperfusion of the involved territory, time
      to treatment within 270 min and good pial collateral formation (large penumbra
      zone) significantly predicted RNI. RNI occurred in 31% of the 112 patients
      studied. RNI occurred in 21/26 (80.8%) patients exhibiting all three favorable
      variables whereas patients with only one favorable variable had a 6.5% chance of
      RNI. 94% of patients displaying RNI had a modified Rankin Scale score of 2 or
      less at 3 months compared with 28.6% without RNI. CONCLUSIONS: RNI following IATT
      for stroke is more likely when at least two of the following are present: good
      reperfusion, good pial collateral formation and treatment within 4.5 h of symptom
      onset, and is strongly predictive of 3 month outcomes. Important to clinical
      management, IATT may need to be reconsidered in patients with poor pial
      collateral formation if time to treatment exceeds 4.5 h.

PMID- 22131437
TI  - Current endovascular treatment options of dural venous sinus thrombosis: a review
      of the literature.
AB  - Dural venous sinus thrombosis, although relatively rare, has the propensity to
      cause potentially fatal conditions, such as stroke. This review presents the
      current endovascular treatment and management options for dural venous sinus
      thrombosis and provides current recommendations. Select databases were utilized
      for an exhaustive literature search with key search terms in efforts to obtain
      all relevant cases to endovascular treatment of dural venous sinus thrombosis.
      Recommendations for management options include initially the use of
      anticoagulation. For patients with a poor prognosis, local thrombolysis with
      urokinase or recombinant tissue plasminogen activator should be initiated.
      Ultimately, if the patient is not a good candidate for local or systemic
      thrombolysis, treatment via rheolytic thrombectomy should be employed.

PMID- 22131439
TI  - Stent retriever technology: concept, application and initial results.
AB  - Stent retrievers are increasingly used for flow restoration and thrombectomy in
      acute embolic stroke. First clinical results support the potential of these new
      devices, in particular the ability to rapidly restore flow and effectively
      retrieve clots from large intracranial arteries, with favorable clinical results
      in preliminary patient series. This article reviews the concept and technical
      aspects of this new technique of endovascular stroke treatment and summarizes the
      first clinical results.

PMID- 22131438
TI  - Occlusive concomitant dissections of the carotid and coronary arteries treated
      with stent placement.
AB  - Spontaneous coronary artery dissection is rare and previously was associated with
      a high mortality rate. Spontaneous dissection of the internal carotid artery is a
      cause of ischemic stroke, especially in young patients. Medical therapy allows
      healing of the carotid dissection in most patients, although endovascular stent
      placement has been reported for the treatment of selected cases. A case is
      reported of a patient in their late 30s who presented with a symptomatic
      occlusive cervical carotid artery dissection and, 7 days later, developed an
      acute coronary syndrome due to an occlusive dissection of the intermediate
      artery. Both lesions were treated with stent placement.

PMID- 22131440
TI  - Reporting standards for angiographic evaluation and endovascular treatment of
      cerebral arteriovenous malformations.
AB  - These guidelines were developed by consensus of a multidisciplinary panel of
      specialists interested in the evaluation and treatment of patients with
      arteriovenous malformations (AVMs) of the CNS. The reporting criteria described
      will serve as a template for trial design and for clinical investigators who wish
      to report on endovascular therapy of cerebral AVMs. Direct comparison of various
      treatment paradigms is important to standardization of care, maximization of good
      treatment outcomes, assessment of new methods and technologies.

PMID- 22131441
TI  - beta-Cell-protective effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid
      as a glutamate dehydrogenase activator in db/db mice.
AB  - 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) is an activator of
      glutamate dehydrogenase (GDH), which is a mitochondrial enzyme with an important
      role in insulin secretion. We investigated the effect of BCH on the high-glucose
      (HG)-induced reduction in glucose-stimulated insulin secretion (GSIS), the
      HG/palmitate (PA)-induced reduction in insulin gene expression, and HG/PA-induced
      beta-cell death. We also studied whether long-term treatment with BCH lowers
      blood glucose and improves beta-cell integrity in db/db mice. We evaluated GSIS,
      insulin gene expression, and DNA fragmentation in INS-1 cells exposed to HG or
      HG/PA in the presence or absence of BCH. An in vivo study was performed in which
      7-week-old diabetic db/db mice were treated with BCH (0.7  g/kg, n = 10) and
      placebo (n = 10) every other day for 6 weeks. After treatment, an intraperitoneal
      glucose tolerance test and immunohistological examinations were performed.
      Treatment with BCH blocked HG-induced GSIS inhibition and the HG/PA-induced
      reduction in insulin gene expression in INS-1 cells. In addition, BCH
      significantly reduced HG/PA-induced INS-1 cell death and phospho-JNK level. BCH
      treatment improved glucose tolerance and insulin secretion in db/db mice. BCH
      treatment also increased the ratio of insulin-positive beta-cells to total islet
      area (P < 0.05) and reduced the percentage of beta-cells expressing cleaved
      caspase 3 (P < 0.05). In conclusion, the GDH activator BCH improved glycemic
      control in db/db mice. This anti-diabetic effect may be associated with improved
      insulin secretion, preserved islet architecture, and reduced beta-cell apoptosis.

PMID- 22131442
TI  - A sphenoid wing meningioma presenting with intraparenchymal and intraventricular
      hemorrhage treated with endovascular embolization alone: case report and
      radiologic follow-up.
AB  - Haemorrhagic presentation of intracranial meningioma is rare, and meningiomas
      with both intraparenchymal hemorrhage and intraventricular extension have not
      been reported. An unusual case of a sphenoid wing meningioma that was treated
      with endovascular embolization alone is presented.

PMID- 22131443
TI  - Acute stent occlusion due to heparin induced thrombocytopenia and thrombosis
      during carotid artery stenting.
AB  - Heparin induced thrombocytopenia and thrombosis is a potential complication of
      any procedure following previous heparin exposure. A case is described of acute
      in-stent occlusion during carotid stenting due to heparin induced
      thrombocytopenia and thrombosis. Management options are also discussed.

PMID- 22131444
TI  - Contribution of the crystalline lens gradient refractive index to the
      accommodation amplitude in non-human primates: in vitro studies.
AB  - The purpose of this study was to determine the contribution of the gradient
      refractive index to the change in lens power in hamadryas baboon and cynomolgus
      monkey lenses during simulated accommodation in a lens stretcher. Thirty-six
      monkey lenses (1.4-14.1 years) and twenty-five baboon lenses (1.8-28.0 years)
      were stretched in discrete steps. At each stretching step, the lens back vertex
      power was measured and the lens cross-section was imaged with optical coherence
      tomography. The radii of curvature for the lens anterior and posterior surfaces
      were calculated for each step. The power of each lens surface was determined
      using refractive indices of 1.365 for the outer cortex and 1.336 for the aqueous.
      The gradient contribution was calculated by subtracting the power of the surfaces
      from the measured lens power. In all lenses, the contribution of the surfaces and
      gradient increased linearly with the amplitude of accommodation. The gradient
      contributes on average 65 +/- 3% for monkeys and 66 +/- 3% for baboons to the
      total power change during accommodation. When expressed in percent of the total
      power change, the relative contribution of the gradient remains constant with
      accommodation and age in both species. These findings are consistent with
      Gullstrand's intracapsular theory of accommodation.

PMID- 22131445
TI  - The resolution of facial expressions of emotion.
AB  - Much is known on how facial expressions of emotion are produced, including which
      individual muscles are most active in each expression. Yet, little is known on
      how this information is interpreted by the human visual system. This paper
      presents a systematic study of the image dimensionality of facial expressions of
      emotion. In particular, we investigate how recognition degrades when the
      resolution of the image (i.e., number of pixels when seen as a 5.3 by 8 degree
      stimulus) is reduced. We show that recognition is only impaired in practice when
      the image resolution goes below 20 * 30 pixels. A study of the confusion tables
      demonstrates that each expression of emotion is consistently confused by a small
      set of alternatives and that the confusion is not symmetric, i.e., misclassifying
      emotion a as b does not imply we will mistake b for a. This asymmetric pattern is
      consistent over the different image resolutions and cannot be explained by the
      similarity of muscle activation. Furthermore, although women are generally better
      at recognizing expressions of emotion at all resolutions, the asymmetry patterns
      are the same. We discuss the implications of these results for current models of
      face perception.

PMID- 22131446
TI  - Covert visual search: prior beliefs are optimally combined with sensory evidence.
AB  - Has evolution optimized visual selective attention to make the best possible use
      of all information available? If so, then Bayesian optimal performance in a
      localization task is achieved by optimally weighting the visual evidence with
      one's prior spatial expectations. In 2 psychophysical experiments, participants
      conducted covert target localization where both visual cues and prior
      expectations were available. The amount of information conveyed by the visual
      evidence was held constant, while the degree of belief was manipulated via
      peripheral cuing (Experiment 1) and spatial probabilities (Experiment 2). A
      number of findings result: (1) People appear to optimally combine slightly biased
      prior beliefs with sensory evidence. (2) These biases are directly comparable to
      those descriptively accounted for by the Prospect Theory. (3) Probabilistic
      information about a target's upcoming location is integrated identically,
      irrespective of whether endogenous or exogenous cuing is used. (4) In
      localization tasks, spatial attention can be understood and quantitatively
      modeled as a set of prior expectations over space that modulate incoming noisy
      sensory evidence.

PMID- 22131447
TI  - Viewing behavior and the impact of low-level image properties across repeated
      presentations of complex scenes.
AB  - Studies on bottom-up mechanisms in human overt attention support the significance
      of basic image features for fixation behavior on visual scenes. In this context,
      a decisive question has been neglected so far: How stable is the impact of basic
      image features on overt attention across repeated image observation? To answer
      this question, two eye-tracking studies were conducted in which 79 subjects were
      repeatedly exposed to several types of visual scenes differing in gist and
      complexity. Upon repeated presentations, viewing behavior changed significantly.
      Subjects neither performed independent scanning eye movements nor scrutinized
      complementary image regions but tended to view largely overlapping image regions,
      but this overlap significantly decreased over time. Importantly, subjects did not
      uncouple their scanning pathways substantially from basic image features. In
      contrast, the effect of image type on feature-fixation correlations was much
      bigger than the effect of memory-mediated scene familiarity. Moreover, feature
      fixation correlations were moderated by actual saccade length, and this
      phenomenon remained constant across repeated viewings. We also demonstrated that
      this saccade length effect was not an exclusive within-subject phenomenon. We
      conclude that the present results bridge a substantial gap in attention research
      and are important for future research and modeling processes of human overt
      attention. Additionally, we advise considering interindividual differences in
      viewing behavior.

PMID- 22131448
TI  - Three-dimensional information in face recognition: an eye-tracking study.
AB  - One unresolved question about face perception is: what is the role of three
      dimensional information in face recognition? In this study, recognition
      performance was compared across changes in viewpoint in different depth
      conditions: a 2D condition without stereo information and a 3D condition where
      stereo information was present (by viewing the same face images as anaglyphs
      through 3D glasses). Subjects' eye movements were recorded during both 3D and 2D
      sessions. The findings revealed that participants were more accurate in the 3D
      condition. Moreover, individual differences in interpupillary distance predicted
      recognition performance in the 3D but not in the 2D condition. A "region of
      interest" analysis of gaze data showed that rich volumetric properties provided
      by certain facial features (e.g., the nose and the cheeks) were attended more in
      the 3D condition compared to the 2D condition. Taken together, these findings
      support the conclusion that face recognition across viewpoint transformation is
      facilitated by the addition of stereoscopic depth cues.

PMID- 22131540
TI  - Computerized visual field defects in posterior cortical atrophy.
AB  - BACKGROUND AND OBJECTIVE: Posterior cortical atrophy (PCA) is a progressive
      neurodegenerative syndrome that presents with cortical visual dysfunction and
      relatively preserved memory. Although higher cortical visual syndromes are well
      known in PCA, visual field defects detected by computerized visual field (CVF)
      perimetry have not been systematically described. The objective of this study was
      to describe CVF defects measured by threshold perimetry in PCA. METHODS: This was
      a retrospective case series of patients meeting proposed PCA diagnostic criteria
      seen in the Neuro-ophthalmology and Neurobehavior Clinics at the University of
      Colorado during 2002 to 2006. History, examination, neuroimaging, autopsy, and
      CVF studies were analyzed. RESULTS: Nine of 11 patients who met the criteria for
      PCA and had CVF testing were included. Seven of the 9 patients had homonymous
      hemianopia or quadrantanopia, and 2 had bilateral constriction. All patients
      progressed to dementia. Criteria were met for probable Alzheimer disease (AD) in
      7, definite AD in 1, and definite dementia with Lewy bodies associated with AD
      pathology in 1. Seven of 9 patients had early and prominent complaints of
      difficulty driving. CONCLUSIONS: CVF defects were characterized by homonymous
      visual field defects or bilateral constriction. Eight of 9 patients progressed to
      probable or definite AD, but the CVF defects were distinctly different from those
      in typical AD. This observation probably reflects a posterior shift of cortical
      pathology to the primary and early secondary visual cortices in PCA. CVF testing
      should be considered in older patients with unexplained visual complaints,
      particularly when associated with difficulty driving, which may indicate the
      possibility of PCA and prompt early neurobehavioral evaluation.

PMID- 22131541
TI  - Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD.
AB  - OBJECTIVE: To compare the diagnostic performance of PET with the amyloid ligand
      Pittsburgh compound B (PiB-PET) to fluorodeoxyglucose (FDG-PET) in discriminating
      between Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD).
      METHODS: Patients meeting clinical criteria for AD (n = 62) and FTLD (n = 45)
      underwent PiB and FDG-PET. PiB scans were classified as positive or negative by 2
      visual raters blinded to clinical diagnosis, and using a quantitative threshold
      derived from controls (n = 25). FDG scans were visually rated as consistent with
      AD or FTLD, and quantitatively classified based on the region of lowest
      metabolism relative to controls. RESULTS: PiB visual reads had a higher
      sensitivity for AD (89.5% average between raters) than FDG visual reads (77.5%)
      with similar specificity (PiB 83%, FDG 84%). When scans were classified
      quantitatively, PiB had higher sensitivity (89% vs 73%) while FDG had higher
      specificity (83% vs 98%). On receiver operating characteristic analysis, areas
      under the curve for PiB (0.888) and FDG (0.910) were similar. Interrater
      agreement was higher for PiB (kappa = 0.96) than FDG (kappa = 0.72), as was
      agreement between visual and quantitative classification (PiB kappa = 0.88-0.92;
      FDG kappa = 0.64-0.68). In patients with known histopathology, overall
      classification accuracy (2 visual and 1 quantitative classification per patient)
      was 97% for PiB (n = 12 patients) and 87% for FDG (n = 10). CONCLUSIONS: PiB and
      FDG showed similar accuracy in discriminating AD and FTLD. PiB was more sensitive
      when interpreted qualitatively or quantitatively. FDG was more specific, but only
      when scans were classified quantitatively. PiB slightly outperformed FDG in
      patients with known histopathology.

PMID- 22131542
TI  - Distal myopathy with upper limb predominance caused by filamin C
      haploinsufficiency.
AB  - OBJECTIVE: In this study, we investigated the detailed clinical findings and
      underlying genetic defect in 3 presumably related Bulgarian families displaying
      dominantly transmitted adult onset distal myopathy with upper limb predominance.
      METHODS: We performed neurologic, electrophysiologic, radiologic, and
      histopathologic analyses of 13 patients and 13 at-risk but asymptomatic
      individuals from 3 generations. Genome-wide parametric linkage analysis was
      followed by bidirectional sequencing of the filamin C (FLNC) gene. We
      characterized the identified nonsense mutation at cDNA and protein level.
      RESULTS: Based on clinical findings, no known myopathy subtype was implicated in
      our distal myopathy patients. Light microscopic analysis of affected muscle
      tissue showed no specific hallmarks; however, the electron microscopy revealed
      changes compatible with myofibrillar myopathy. Linkage studies delineated a 9.76
      Mb region on chromosome 7q22.1-q35 containing filamin C (FLNC), a gene previously
      associated with myofibrillar myopathy. Mutation analysis revealed a novel
      c.5160delC frameshift deletion in all patients of the 3 families. The mutation
      results in a premature stop codon (p.Phe1720LeufsX63) that triggers nonsense
      mediated mRNA decay. FLNC transcript levels were reduced in muscle and
      lymphoblast cells from affected subjects and partial loss of FLNC in muscle
      tissue was confirmed by protein analysis. CONCLUSIONS: The FLNC mutation that we
      identified is distinct in terms of the associated phenotype, muscle morphology,
      and underlying molecular mechanism, thus extending the currently recognized
      clinical and genetic spectrum of filaminopathies. We conclude that filamin C is a
      dosage-sensitive gene and that FLNC haploinsufficiency can cause a specific type
      of myopathy in humans.

PMID- 22131543
TI  - A practical approach to incidental findings in neuroimaging research.
AB  - OBJECTIVE: We describe the systematic approach to incidental findings (IFs) used
      at the Mind Research Network (MRN) where all MRI scans receive neuroradiologist
      interpretation and participants are provided results. METHODS: From 2004 to 2011,
      8,545 MRI scans were acquired by 45 researchers. As mandated by MRN's external
      institutional review board, all structural sequences were evaluated by a clinical
      neuroradiologist who generated a report that included recommendations for
      referral if indicated. Investigators received a copy of their participants'
      reports, which were also mailed to participants unless they specifically
      declined. To better understand the impact of the radiology review process, a
      financial analysis was completed in addition to a follow-up phone survey to
      characterize participant perceptions regarding receiving their MRI scan results.
      RESULTS: The radiologist identified IFs in 34% of the 4,447 participants. Of
      those with IFs (n = 1,518), the radiologist recommended urgent or immediate
      referral for 2.5% and routine referral for 17%. For 80.5%, no referral was
      recommended. Estimated annual cost for this approach including support for the
      neuroradiologist, medical director, and ancillary staff is approximately $60,000
      or $24/scan. The results of the retrospective phone survey showed that 92% of
      participants appreciated receiving their MRI report, and the majority stated it
      increased their likelihood of volunteering for future studies. CONCLUSIONS:
      Addressing IFs in a cost-effective and consistent manner is possible by adopting
      a policy that provides neuroradiology interpretation and offers participant
      assistance with clinical follow-up when necessary. Our experience suggests that
      an ethical, institution-wide approach to IFs can be implemented with minimal
      investigator burden.

PMID- 22131545
TI  - A tale of two tracers: the age of wisdom for dementia diagnosis?

PMID- 22131544
TI  - Muscle cramp in pediatric Charcot-Marie-Tooth disease type 1A: prevalence and
      predictors.
AB  - OBJECTIVES: To identify correlates of calf cramp in children with Charcot-Marie
      Tooth disease type 1A (CMT1A). METHODS: Throughout Australia, 81 children aged 2
      16 years with CMT1A were recruited. Measures of strength, ankle range, foot
      posture, balance, agility, endurance, gait, and neurophysiology were collected.
      Post hoc logistic regression analyses were performed to identify independent
      predictors of calf cramp. RESULTS: Of the 81 children, 26 (32%) reported calf
      cramp, and 1 child each reported toe, quadriceps, or arm cramp. Calf cramp was
      associated (p < 0.05) with older age; the presence of hand tremor; stronger foot
      inversion, eversion, dorsiflexion, and plantarflexion; and better performance in
      long-jump and 9-hole peg tests. Logistic regression analysis revealed only
      increasing age (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.11-1.58; p =
      0.002) and the presence of hand tremor (OR 3.81, 95% CI 1.18-12.56; p = 0.028) as
      independent predictors of calf cramp. CONCLUSION: Calf cramps are common in
      children with CMT1A and worsen with age. This study revealed a previously
      unrecognized link between cramp and hand tremor in children with CMT1A. Further
      investigation of proposed mechanisms and risk factors common to both cramp and
      tremor will contribute to our understanding of these common complications of
      CMT1A.

PMID- 22131546
TI  - The fraction of alpha-linolenic acid present in the sn-2 position of structured
      triacylglycerols decreases in lymph chylomicrons and plasma triacylglycerols
      during the course of lipid absorption in rats.
AB  - Little is known about the ability of alpha-linolenic acid (Ln) to remain in the
      sn-2 position of TG during the absorption process. The goal of this study was to
      determine the Ln distribution in the lymph (Study 1) and plasma (Study 2) TG of
      rats fed a single i.g. load of structured TG [300 mg/rat of either oleic acid
      (O)/Ln/O TG (OLnO) or Ln/O/O TG (LnOO), n = 7 rats]. In an early fraction (3-4 h)
      of lymph (OLnO group; 100% Ln in the sn-2 position), 46 +/- 2% Ln was maintained
      in this position in lymph TG. There was even less (29 +/- 6%) in the last
      fraction (7-24 h) (P < 0.05). Ln was also found (9 +/- 3%) in the sn-2 position
      of lymph TG in the LnOO group. The Ln content in lymph phospholipids was twice as
      high in rats when they were fed LnOO (4.2 +/- 0.1%) than OLnO (2.3 +/- 0.2%) (P <
      0.005). Six hours postprandially (Study 2), 21 +/- 3% of the Ln incorporated into
      plasma TG was located in the sn-2 position in the OLnO group compared to 13 +/-
      2% in the LnOO group (P < 0.001). Overall, these results indicate that the amount
      of Ln that moved from the sn-2 position of structured TG to the sn-1(3) position
      of lymph TG increased during absorption. This may account for a substantial
      hydrolysis of the 2-monolinolenylglycerols in enterocytes, leading to the
      intramolecular redistribution of Ln in lymph TG and, consequently, in plasma TG.

PMID- 22131547
TI  - Program experience with micronutrient powders and current evidence.
AB  - The efficacy of micronutrient powders (MNP) in the treatment of anemia in
      moderately anemic children aged 6-24 mo has been clearly demonstrated. The
      evidence of the effectiveness of MNP in large-scale programs, however, is scarce.
      This article describes the program experience and findings of large-scale MNP
      distribution in refugee camps and in an emergency context in Bangladesh, Nepal,
      and Kenya. The MNP contained 15-16 micronutrients as per the WHO/World Food
      Programme/UNICEF joint statement, whereas the iron content was reduced to 2.5 mg
      from NaFeEDTA in a malaria-endemic area in Kenya. Hundreds of thousands of
      children aged 6-59 mo and pregnant and lactating women were targeted to consume
      MNP either daily or every other day over an extended period of time. Extensive
      social marketing campaigns were undertaken to promote regular use of the product.
      A number of studies were embedded in the programs to assess the impact of MNP on
      the nutritional status of target beneficiaries. Some improvements in anemia
      prevalence estimates were observed in particular subgroups, but other results did
      not show significant improvements. A significant decrease in the prevalence of
      stunting was observed in Nepal and Kenya but not in Bangladesh. Diarrhea episodes
      decreased significantly among children receiving MNP in Nepal. A key challenge is
      to ensure high MNP acceptance and adherence among beneficiaries. Investigation of
      non-nutritional causes of anemia is warranted in settings with high compliance
      but no improvement in hemoglobin status. Further investigation into the most
      appropriate manner to use MNP in malaria endemic settings is warranted.

PMID- 22131548
TI  - Identifying potential programs and platforms to deliver multiple micronutrient
      interventions.
AB  - This article reviews the potential of four broad types of platforms, health,
      agriculture, market-based, and social protection programs, to deliver multiple
      micronutrient (MMN) interventions (supplementation, fortification, and dietary
      modification). We assessed the platforms' potential based on seven performance
      criteria related to programs within these platforms: 1) targeting, 2) efficacy of
      interventions, 3) quality of implementation, 4) utilization, 5) impact, 6)
      coverage, and 7) sustainability. We highlight one type of program per platform to
      illustrate strengths and weaknesses for delivering MMN interventions, identify
      critical knowledge gaps, and highlight what is needed to increase effectiveness
      for delivering MMN interventions. We found that all four platforms have the
      potential to effectively deliver MMN interventions if the following key program
      elements are addressed: 1) strong behavior change communication strategies to
      increase demand and proper utilization of services/products; 2) supply side
      interventions to ensure consistent availability of high quality interventions,
      products, and well-trained staff; 3) rigorous evaluations of effectiveness,
      quality of delivery, and impact pathways to generate best practices for
      replication and scale-up; and 4) timely dissemination of evaluation results to
      ensure use by program implementers and policy makers. The diversification of
      delivery platforms, which simultaneously addresses multiple determinants of MMN
      deficiencies and expands coverage, is needed to accelerate progress in reducing
      MMN deficiencies.

PMID- 22131550
TI  - Breast milk vitamin B-12 concentrations in Guatemalan women are correlated with
      maternal but not infant vitamin B-12 status at 12 months postpartum.
AB  - In our previous studies, one-third of lactating Guatemalan women, infants, and
      children had deficient or marginal serum vitamin B-12 concentrations.
      Relationships among maternal and infant status and breast milk vitamin B-12,
      however, have not, to our knowledge, been investigated in such populations. Our
      purpose was to measure breast milk vitamin B-12 in Guatemalan women with a range
      of serum vitamin B-12 concentrations and explore associations between milk
      vitamin B-12 concentrations and maternal and infant vitamin B-12 intake and
      status. Participants were 183 mother-infant pairs breastfeeding at 12 mo
      postpartum. Exclusion criteria included mother <17 y, infant <11.5 or >12.5 mo,
      multiple birth, reported health problems in mother or infant, and mother pregnant
      >3 mo. Data collected on mothers and infants included anthropometry, serum and
      breast milk vitamin B-12, and dietary vitamin B-12. Serum vitamin B-12
      concentrations indicated deficiency (<150 pmol/L) in 35% of mothers and 27% of
      infants and marginal status (150-220 pmol/L) in 35% of mothers and 17% of
      infants. In a multiple regression analysis, breast milk vitamin B-12
      concentration was associated (P < 0.05) with both maternal vitamin B-12 intake (r
      = 0.26) and maternal serum vitamin B-12 (r = 0.30). Controlling for the number of
      breastfeeds per day and vitamin B-12 intake from complementary foods, infant
      serum vitamin B-12 was associated with maternal serum vitamin B-12 (r = 0.31; P <
      0.001) but not breast milk vitamin B-12, implicating a long-term effect of
      pregnancy status on infant vitamin B-12 status at 12 mo postpartum.

PMID- 22131549
TI  - Th17 cell accumulation is decreased during chronic experimental colitis by (n-3)
      PUFA in Fat-1 mice.
AB  - During colon inflammation, Th17 cells and immunosuppressive regulatory T cells
      (Treg) are thought to play promotive and preventative roles, respectively.
      Dietary (n-3) PUFA favorably modulate intestinal inflammation in part by
      downregulating T-cell activation and functionality. We used the Fat-1 mouse, a
      genetic model that synthesizes long-chain (n-3) PUFA de novo, to test the
      hypothesis that (n-3) PUFA protect against colonic inflammation by modulating the
      polarization of Treg and Th17 cells during colitis. Male and female wild-type
      (WT) and Fat-1 mice were administered dextran sodium sulfate (DSS) in the
      drinking water (2.5%) to induce acute (5 d DSS) or chronic (3 cycles DSS) colitis
      and the percentage of Treg and Th17 cells residing locally [colonic lamina
      propria (cLP)] and systemically (spleen) was determined by flow cytometry. The
      percentage of Treg in either tissue site was unaffected by genotype (P > 0.05);
      however, during chronic colitis, the percentage of Th17 cells residing in both
      the spleen and cLP was lower in Fat-1 mice compared to WT mice (P < 0.05).
      Colonic mucosal mRNA expression of critical Th17 cell cytokines and chemokine
      receptors (IL-17F, IL-21, and CCR6) were lower, whereas expression of the Th17
      cell suppressive cytokine, IL-27, was greater in Fat-1 mice compared to WT mice
      during chronic colitis (P < 0.05). Moreover, colon histological scores were
      improved in Fat-1 mice (P < 0.05). Collectively, these results demonstrate for
      the first time, to our knowledge, that (n-3) PUFA can modulate the colonic
      mucosal microenvironment to suppress Th17 cell accumulation and inflammatory
      damage following the induction of chronic colitis.

PMID- 22131551
TI  - Identifying nutritional need for multiple micronutrient interventions.
AB  - Micronutrient deficiency remains a major public health problem in many countries
      worldwide with important consequences for the health of the population and child
      growth and development. The objective of this article is to review information
      that should be taken into consideration in identifying the need for and in
      designing micronutrient programs. We review information that could be used to
      identify nutritional need, including the prevalence of deficiency and evidence of
      inadequate dietary intake as well as potential data sources and some strengths
      and weakness of such data for program decision-making. We also review factors
      that might modify the potential impact of programs and that should therefore be
      taken into consideration in their design. For example, such factors may include
      access to formal and informal health systems, quality of health provider
      training, and behavior change communication and complementary or overlapping
      interventions. Nationally representative data on micronutrient deficiencies and
      dietary intake are most useful for identifying unmet needs. Although the burden
      of micronutrient deficiencies lies in low-income countries, few have detailed
      information on specific deficiencies beyond anemia, and nationally representative
      dietary intake data are scarce. Nationally representative data may still mask
      considerable within-country variability by geographic, economic, or ethnic group.
      Some efforts designed to promote coordination in nutrition programming within
      countries utilizing information on prevalence, intake, and program coverage and
      utilization are also reviewed. Improving the quality of such data and ensuring
      continual updates are vital to guide decision making and to ensure that programs
      can appropriately respond to needs.

PMID- 22131552
TI  - Use of nutritional biomarkers in program evaluation in the context of developing
      countries.
AB  - The Lancet series on maternal and child undernutrition emphasized the need for
      accurate and reliable biomarkers that reflect nutrient status and measure the
      impact of interventions. An initiative called Biomarkers of Nutrition for
      Development (BOND) by the Eunice Kennedy Shriver National Institute of Child
      Health and Human Development aims to provide guidance for the selection and
      interpretation of biomarkers that meet a range of interests, including research,
      clinical policy, and program development. This article summarizes the activities
      of the program working group of the BOND initiative. The working group specified
      biomarkers according to program objectives such as assessing the nutritional
      situation or status of target populations/areas; monitoring progress of
      intervention; and evaluating program impact. In addition, the biomarkers
      developed were required to be feasible in the field settings. Based on these
      considerations, population-based biomarkers for programs are proposed for case
      examples of vitamin A, folate, vitamin B-12, iron, and zinc. Biomarkers of
      underlying infection/inflammation, anthropometric measures of growth, and dietary
      intake are recommended to be included. A program manager guide and future
      research to develop biomarkers for program context are recommended.

PMID- 22131553
TI  - Susceptibility to overeating affects the impact of savory or sweet drinks on
      satiation, reward, and food intake in nonobese women.
AB  - Taste is involved in food preference and choice, and it is thought that it can
      modulate appetite and food intake. The present study investigated the effect of
      savory or sweet taste on satiation, reward, and food intake and according to
      individual differences in eating behavior traits underlying susceptibility to
      overeating. In a crossover design, 30 women (BMI = 22.7 +/- 2.3; age = 21.9 +/-
      2.6 y) consumed a fixed energy preload (360 kJ/g) with a savory, sweet, or bland
      taste before selecting and consuming items from a test meal ad libitum.
      Sensations of hunger were used to calculate the satiating efficiency of the
      preloads. A computerized task was used to examine effects on food reward
      (explicit liking and implicit wanting). The Three Factor Eating Questionnaire was
      used to compare individual differences in eating behavior traits. Satiation and
      total food intake did not differ according to preload taste, but there was an
      effect on explicit liking and food selection. The savory preload reduced liking
      and intake of high-fat savory foods compared to sweet or bland preloads. The
      eating behavior trait disinhibition interacted with preload taste to determine
      test meal intake. Higher scores were associated with increased food intake after
      the sweet preload compared to the savory preload. Independent of preload taste,
      disinhibition was associated with lower satiating efficiency of the preloads and
      enhanced implicit wanting for high-fat sweet food. Savory taste has a stronger
      modulating effect on food preference than sweet or bland taste and may help to
      preserve normal appetite regulation in people who are susceptible to overeating.

PMID- 22131554
TI  - Exposure to metal-working fluids in the automobile industry and the risk of male
      germ cell tumours.
AB  - INTRODUCTION: In a previous analysis of a case-control study of testicular cancer
      nested in a cohort of automobile workers, we observed an increased risk for
      testicular cancer among workers who had ever been involved in occupational metal
      cutting tasks. We investigated whether this risk increase was due to exposure to
      metal-working fluids (MWF). METHODS: Occupational exposure to MWF was assessed in
      detail using a job-specific questionnaire for metal-cutting work. We calculated
      ORs and associated 95% CIs individually matched for age (+/-2 years) and adjusted
      for a history of cryptorchidism by conditional logistic regression. RESULTS: The
      prevalence of exposure to MWF was 39.8% among cases and 40.1% among controls. For
      total germ cell tumours and seminomas we did not observe risk increases for metal
      cutting tasks or occupational exposure to MWF (OR 0.95; 95% CI 0.69 to 1.32 and
      OR 0.88; 95% CI 0.58 to 1.35, respectively). However, dermal exposure to oil
      based MWF was associated with an increased risk for non-seminomatous testicular
      cancer. Dermal exposure to oil-based MWF for more than 5000 h showed particularly
      high risk estimates (OR 4.72; 95% CI 1.48 to 15.09). DISCUSSION: Long-term dermal
      exposure to oil-based MWF was a risk factor for the development of non
      seminomatous testicular germ cell cancer. Possible measures to reduce exposure
      include the introduction of engineering control measures such as venting or
      enclosing of machines, and enforcing the use of personal protective equipment
      during metal cutting.

PMID- 22131555
TI  - Oxidative Stability of Polyunsaturated Edible Oils Mixed With Microcrystalline
      Cellulose.
AB  - The oxidative stability of mixtures of edible oils containing polyunsaturated
      fatty acids (PUFA) and microcrystalline cellulose (MCC) was investigated. The
      mixtures studied consisted of oils of either camelina (CAM), cod liver (CLO), or
      salmon (SO) mixed with either colloidal or powdered MCC. A 50:50 (w/w) ratio of
      oil:MCC resulted in an applicable mixture containing high levels of PUFA edible
      oil and dietary fiber. The oxidative stability of the formulated mixtures and the
      pure oils was investigated over a period of 28 days. The peroxide value (PV) was
      assessed as a parameter for primary oxidation products and dynamic headspace gas
      chromatography mass spectrometry (GC/MS) was used to analyze secondary volatile
      organic compounds (VOC). CAM and the respective mixtures were oxidatively stable
      at both 4 and 22  degrees C during the storage period. The marine oils and the
      respective mixtures were stable at 4  degrees C. At 22  degrees C, an increase in
      hydroperoxides was found, but no increase in VOC was detected during the time
      frame investigated. At 42  degrees C, prominent increases in PV and VOC were
      found for all oils and mixtures. Hexanal, a common marker for the degradation of
      n-6 fatty acids, propanal and 2,4-heptadienal (E,E), common indicators for the
      degradation of n-3 fatty acids, were among the volatiles detected in the
      headspace of oils and mixtures. This study showed that a mixture containing a
      50:50 ratio of oil:MCC can be obtained by a low-tech procedure that does not
      induce oxidation when stored at low temperatures during a period of 1 month.

PMID- 22131556
TI  - Sociology and American Studies: A Case Study in the Limits of
      Interdisciplinarity.
AB  - American Studies is an academic discipline whose object of study is the United
      States of America and everything associated with it, and American sociologists
      largely ignore it. American Studies largely ignores American sociology. What
      causes this mutual exclusion? An outline of the disciplinary history of American
      Studies and journal article citation data show that the relationship between
      sociology and American Studies is weak and asymmetrical; American Studies cites
      sociology more often, but very little and not by much. I argue that mutual
      exclusion is due to mutual distrust in methods: sociology sees itself as a
      science, while American Studies, with roots in history and literature, does not.
      This article serves as a case study in the limits of interdisciplinarity.

PMID- 22131557
TI  - Kent Stuber DC, MSc.

PMID- 22131558
TI  - Dr. Mana Rezai DC, PhD Candidate.

PMID- 22131559
TI  - Dr. Maja Stupar DC, PhD Candidate.

PMID- 22131560
TI  - Treatment of post-traumatic myositis ossificans of the anterior thigh with
      extracorporeal shock wave therapy.
AB  - OBJECTIVE: This case study demonstrates the effectiveness of a novel approach to
      the treatment of post-traumatic myositis ossificans with extracorporeal shockwave
      therapy in an elite athlete. CLINICAL FEATURES: A 20 year-old male semi
      professional rugby player presented with progressive pain and loss of range of
      motion after sustaining a severe, right quadriceps contusion nine weeks earlier.
      The differential diagnosis of myositis ossificans was suspected and confirmed on
      radiographic examination. INTERVENTION AND OUTCOME: A two week treatment protocol
      was undertaken consisting of three sessions of extracorporeal shockwave therapy
      and an unsupervised exercise program consisting of active and passive range of
      motion, gradual strengthening and balance exercises. The patient experienced
      appreciable improvements in pain and range of motion in two weeks and was able to
      participate in sport specific activity four weeks after presentation. SUMMARY:
      This case illustrates the successful conservative management of post-traumatic
      myositis ossificans of the anterior thigh with extracorporeal shockwave therapy
      and a primarily unsupervised graded exercise program within a condensed treatment
      time frame of 2 weeks.

PMID- 22131561
TI  - Avulsion fractures of the pelvis - a qualitative systematic review of the
      literature.
AB  - OBJECTIVE: To assess a causal relationship between physical activity or boney
      surgical intervention and the occurrence of avulsion fracture in the pelvis.
      Secondarily to assess the average age at which avulsion fracture occurs in cases
      associated with physical activity or boney surgery. METHOD: A literature search
      was performed on a variety of databases using text words and MeSH terms. Results
      were limited to English language. Cases involving trauma or pathological disease
      were excluded. Causation Criteria scores were calculated for each paper to
      establish a link between the suspected mechanism of injury and avulsion fracture.
      RESULTS: 48 papers were retrieved encompassing 66 cases of avulsion fracture. 88%
      of cases were associated with physical activity while 12% were associated with a
      history of surgery. Average age in the physical activity cases was 16.8(range 13
      43) and 56.4(range 31-74) in the surgery related cases. Causation Criteria scores
      were definite in 76% of activity related cases and probable in 60% of boney
      surgery related cases. CONCLUSIONS: Avulsion fractures of the pelvis represent a
      highly prevalent pathology among the adolescent athletic population. A population
      of skeletally mature patients with history of boney surgical intervention are
      also at risk.

PMID- 22131562
TI  - The effects of aerobic physical activity on adiposity in school-aged children and
      youth: a systematic review of randomized controlled trials.
AB  - CONTEXT: The role of aerobic physical activity as a standalone treatment in
      decreasing adiposity in school-aged children and youth has not been well
      established. OBJECTIVE: To systematically search and assess the quality of the
      literature on the efficacy of aerobic physical activity to decrease adiposity in
      school-aged children and youth. METHODS: An electronic search strategy was
      conducted in EBSCO databases, including MEDLINE and CINAHL. Retrieved articles
      that met the eligibility criteria were rated for methodological quality by using
      the Downs and Black checklist. RESULTS: 10 articles met the inclusion criteria in
      the form of RCTs. Results indicate that five articles had positive results in
      decreasing adiposity compared to controls and five articles had no change in
      adiposity compared to controls. CONCLUSION: There is a paucity of evidence to
      support aerobic physical activity as a successful standalone treatment for
      decreasing adiposity. Despite the heterogeneity of the methods there is some
      evidence to support that school-aged children and youth benefit from aerobic
      physical activity to decrease adiposity and to limit weight gain.

PMID- 22131563
TI  - Chronic Achilles tendinopathy: a case study of treatment incorporating active and
      passive tissue warm-up, Graston Technique, ART, eccentric exercise, and
      cryotherapy.
AB  - OBJECTIVE: To describe the subjective pain and functional improvements of a
      patient with chronic Achilles tendinopathy following a treatment plan
      incorporating active and passive tissue warm-up, followed respectively by soft
      tissue mobilization utilizing both Graston Technique((r)) and Active Release
      Techniques((r)), eccentric exercise, and static stretching in combination with
      cryotherapy. BACKGROUND: The primary characterization of chronic Achilles
      tendinopathy is gradual onset of pain and dysfunction focused in one or both
      Achilles tendons arising secondary to a history of repetitive use or excessive
      overload. INTERVENTION AND OUTCOME: Conservative treatment is commonly the
      initial strategy for patient management. Tissue heating, soft tissue
      mobilization, eccentric training, and static stretching with cryotherapy were
      implemented to reduce pain and improve function. SUMMARY: A specific protocol of
      heat, soft tissue mobilization, eccentric exercise, stretching, and cryotherapy
      appeared to facilitate a rapid and complete recovery from chronic Achilles
      tendinopathy.

PMID- 22131564
TI  - Utilization of Vascular Restriction Training in post-surgical knee
      rehabilitation: a case report and introduction to an under-reported training
      technique.
AB  - INTRODUCTION: The objective of this paper is to introduce a new and reportedly
      safe training technique, utilizing a vascular restriction stimulus during low
      intensity rehabilitative exercise and provide a case example within a post
      surgical rehabilitation scenario. A brief review of the most commonly reported
      mechanisms of action behind the purported success of the training stimulus is
      included. METHODS: 19-year-old athlete presented for an accelerated post
      operative knee rehabilitation program. She received a commonly utilized
      rehabilitation program that was supplemented with vascular restriction stimulus.
      RESULTS: The patient maintained muscle cross-sectional area and had improved
      function at a 12-week follow-up. CONCLUSION: Low intensity exercise supplemented
      with vascular restriction may prove to be an efficient and effective means of
      maintaining post-surgical muscle size and subjective knee function.

PMID- 22131565
TI  - Heel pain due to psoriatic arthritis in a 50 year old recreational male athlete:
      case report.
AB  - Heel pain is a common presentation in a sports injury practice, with a list of
      common differentials including achilles tendinopathy and retrocalcaneal bursitis.
      However, seronegative arthritis can also cause enthesopathies that produce heel
      pain and should be considered in a differential diagnosis list. In this case, a
      50 year old recreationally active male presented with non-traumatic insidious
      heel pain and without history of any skin conditions or any other symptoms of
      seronegative spondyloarthritis. Clinical suspicion led to laboratory testing and
      radiographs/bone scan which yielded the diagnosis of psoriatic arthritis.

PMID- 22131566
TI  - Intraosseous ganglion cyst of the humeral head in a competitive flat water
      paddler: case report.
AB  - OBJECTIVE: To present the diagnostic and clinical features of an intraosseous
      ganglion cyst of the humeral head of a female flat water canoe athlete. CLINICAL
      FEATURES: An 18-year old female flat water canoeist complaining of right shoulder
      pain following a strenuous paddling training camp. INTERVENTION AND OUTCOME: A
      trial of passive care was conducted, including soft tissue therapy, spinal
      manipulative therapy, acupuncture, and rehabilitation. The patient seemed to be
      responding with treatment, but pain would always resume with paddling. A
      diagnostic ultrasound displayed mild thickening and effusion in the
      subacromial/subdeltoid bursae. Continued passive care was not able to resolve the
      symptoms and she underwent an MRI which revealed an intraosseus ganglion cyst
      subjacent to the lesser tuberosity and floor of the intertubercular groove. A
      subsequent MRA was ordered to assess the labrum, which was intact, but the cyst
      had progressed in size. She was referred to an orthopedic surgeon who performed
      surgery. CONCLUSION: An IOG cyst within the humeral head is a rare, potentially
      painful condition that can mimic other pathologies including impingement and
      labral tear. It is important to be aware of the clinical features to obtain a
      prompt diagnosis and appropriate treatment of this condition.

PMID- 22131567
TI  - Acute compartment syndrome of the foot in a soccer player: a case report.
AB  - OBJECTIVE: To present the diagnostic and clinical features including management
      of acute compartment syndrome (ACS) of the foot and to create a sense of
      emergency amongst clinicians of this rare and dangerous condition. CLINICAL
      FEATURES: A 28-year old male soccer player on acetylsalicylic acid (ASA) and
      verapamil presented with severe swelling, paresthesia, and pain in the left ankle
      after an acute grade three-inversion ankle sprain. A diagnosis of foot
      compartment syndrome was made. INTERVENTION AND OUTCOME: A fasciotomy was not
      performed and subsequent neurological sequelae occurred. We hypothesize that the
      edema caused by the ankle sprain was excessive due to the use of ASA and
      verapamil, resulting in increased compartmental pressure and neurological signs
      in the foot. SUMMARY: Although rare, it is extremely important to be aware of the
      clinical features of ACS of the foot to obtain an appropriate diagnosis and
      manage this medical emergency promptly.

PMID- 22131568
TI  - Growth Restart/Recovery Lines involving the vertebral body: a rare, incidental
      finding and diagnostic challenge in two patients.
AB  - OBJECTIVE: To present the phenomenon of growth restart lines and create awareness
      of the possible differential diagnoses. CLINICAL FEATURES: Two case reports
      outlining the presentation of growth restart lines found in the vertebrae of
      trampolinists. Emphasis in each case is placed on correlating the patient history
      with radiographic findings. INTERVENTION AND OUTCOME: In both cases a
      conservative chiropractic treatment plan was initiated once the differential
      diagnoses could be ruled out. CONCLUSION: Although the range of etiologies of
      growth restart lines is extensive, these case reports illustrate the importance
      of a comprehensive case history when presented with the radiographic finding of
      growth restart lines.

PMID- 22131569
TI  - Weight cycling in adolescent Taekwondo athletes.
AB  - BACKGROUND: Weight reduction cycles are used by weight classed athletes in
      Taekwondo to make a weight category. Tension, dizziness, headaches, and confusion
      have been associated with rapid weight loss (RWL). There is a lack of research in
      weight cycling and its benefits among Taekwondo athletes. PURPOSE: To investigate
      the rate of weight cycling in Junior Taekwondo athletes and its effect on
      performance. METHODS: Athletes were weighed prior to competition, then again
      before their first match. Body mass difference in relation to winning was
      compared. RESULTS: A significant increase from weigh-in to pre-match measurements
      was consistently found in both genders with no significant difference between
      them. Winners had a mean body mass gain (1.02 kg) which was non-significantly
      less than the non-winners (1.09 kg). CONCLUSIONS: RWL practices do not define
      which athlete will perform better. Negative effects of weight cycling coupled
      with RWL has unclear performance benefits which indicates a need for further
      research.

PMID- 22131570
TI  - Lateral epicondylosis and calcific tendonitis in a golfer: a case report and
      literature review.
AB  - OBJECTIVE: To detail the progress of a young female amateur golfer who developed
      chronic left arm pain while playing golf 8 months prior to her first treatment
      visit. CLINICAL FEATURES: Findings included pain slightly distal to the lateral
      epicondyle of the elbow, decreased grip strength, and positive orthopedic
      testing. Diagnostic ultrasound showed thickening of the common extensor tendon
      origin indicating lateral epicondylosis. Radiographs revealed an oval shaped
      calcified density in the soft tissue adjacent to the lateral humeral epicondyle,
      indicating calcific tendonitis of the common extensor tendon origin. INTERVENTION
      AND OUTCOME: Conventional care was aimed at decreasing the repetitive load on the
      common extensor tendon, specifically the extensor carpi radialis brevis. Soft
      tissue techniques, exercises and stretches, and an elbow brace helped to reduce
      repetitive strain. Outcome measures included subjective pain ratings, and follow
      up imaging 10 weeks after treatment began. CONCLUSION: A young female amateur
      golfer with chronic arm pain diagnosed as lateral epicondylosis and calcific
      tendonitis was relieved of her pain after 7 treatments over 10 weeks of soft
      tissue and physical therapy focusing specifically on optimal healing and
      decreasing the repetitive load on the extensor carpi radialis brevis.

PMID- 22131571
TI  - Coumatetralyl rodenticide induced pericardial effusion - a comment.

PMID- 22131573
TI  - Advanced dental local nerve block anesthesia - a comment.

PMID- 22131574
TI  - CVJ readership survey.

PMID- 22131575
TI  - An ethicist's commentary on the credibility of animal care and use committees.

PMID- 22131576
TI  - Using foresight to prepare animal health today for tomorrow's challenges.
AB  - Foresight has been introduced in Canada in the area of animal health as a process
      to broaden thinking about the future and inform policy development. Its initial
      use and evolution through projects and studies over the past decade are
      described, demonstrating real action in animal health. Despite positive,
      continuing, and exciting results in animal health policy development, foresight's
      widespread acceptance and use thus far have been limited. Critical components for
      success, drawn from the Canadian experience, are described, and recommendations
      are offered for further action in animal health.

PMID- 22131577
TI  - Leptospirosis in beef herds from western Canada: serum antibody titers and
      vaccination practices.
AB  - One study described the frequency of pre-breeding vaccination for leptospirosis
      in 205 cow-calf herds from across western Canada and the prevalence of positive
      Leptospira antibody titers in unvaccinated, weaned calves from 61 of these herds.
      The percentages of herds vaccinated for leptospirosis were 13.7% in 2001 and 8.4%
      in 2002. Of 1539 calves examined, 13 (0.8%) had a positive antibody titer for a
      Leptospira serovar; the most common serovar detected was hardjo. A second study
      examined the prevalence of positive Leptospira antibody titers during the summer
      grazing season in 313 vaccinated and 478 unvaccinated cows from 40 cow-calf herds
      in southern Saskatchewan. Antibody titers for 7 Leptospira serovars were measured
      during the grazing season. Of the non-vaccinated cows, 9.6% were positive in the
      spring for serovar pomona, 6.7% for serovar grippotyphosa, and 6.1% for serovar
      icterohaemorrhagiae; the corresponding percentages for the fall were 5.5%, 3.0%,
      and 1.3%, respectively. Of 781 vaccinated and unvaccinated cows that were sampled
      twice, 11.3% of vaccinated cows and 2.3% of unvaccinated cows had increases in
      Leptospira antibody titers during the grazing season.

PMID- 22131578
TI  - Clinical investigation of local implantation of gentamicin-impregnated collagen
      sponges in dogs.
AB  - The purpose of this study was to evaluate the effects on health and kidney
      function of local implantation of commercial gentamicin-impregnated collagen
      sponges. Four healthy dogs were submitted to local surgical implantation of
      collagen impregnated sponges. Follow-up with serial physical examinations and
      measurements of serum creatinine, urea nitrogen, and gentamicin were performed
      for 7 d. There were no adverse reactions, or changes in measurements of kidney
      function.

PMID- 22131579
TI  - Middle ear cholesteatoma in 11 dogs.
AB  - Middle ear cholesteatoma is a rare condition in dogs with chronic otitis.
      Otorrhea, otodinia, and pain on temporomandibular joint palpation are the most
      common clinical signs. Neurological abnormalities are often detectable. Computed
      tomography reveals the presence of an expansive and invasive unvascularized
      lesion involving the tympanic cavity and the bulla, with little or no contrast
      enhancement after administration of contrast mediu. Video-otoscopy may detect
      pearly growth or white/yellowish scales in the middle ear cavity. Surgery is the
      only therapy but is associated with a high risk of recurrence.

PMID- 22131580
TI  - Ovariohysterectomy in a dog by a hybrid NOTES technique.
AB  - This report demonstrates the feasibility of an elective
      ovariosalpingohysterectomy by natural transluminal endoscopic surgery (NOTES)
      hybrid technique in a dog. A 5-mm abdominal cannula was used in combination with
      a 10-mm cannula (vaginal access). The patient's quick recovery and the absence of
      complications are indicative of the effectiveness of this surgery.

PMID- 22131581
TI  - An unusual clinical presentation of a dog with gastrinoma.
AB  - Gastrinoma is a rare malignant neuroendocrine neoplasia that results in
      autonomous gastrin secretion that stimulates hypersecretion of gastric acid,
      resulting in severe gastric and proximal small intestinal ulcerations. The
      principal clinical manifestation of gastrinoma is persistent vomiting. This
      report describes an uncommon manifestation of pancreatic gastrinoma in a dog.

PMID- 22131582
TI  - Multicystic dysplastic kidney disease in a dog.
AB  - A 1-year-old female mongrel dog was evaluated for anorexia and vomiting of 4 days
      duration. Abdominal ultrasonographic findings revealed small kidneys with
      multiple anechoic cysts. The dog was euthanized due to poor prognosis. A full
      necropsy was performed, and the histopathologic findings were consistent with
      multicystic dysplastic kidney disease.

PMID- 22131583
TI  - Transtumoral plating as a novel method for palliative limb spare and
      thromboembolism in a dog with a distal radial primary bone tumor.
AB  - A 7-year-old, spayed, female great Pyrenees with a primary tumor of the distal
      radius was treated with placement of a bone plate that spanned the tumor. The
      goals were palliation and prevention of pathologic fracture. This is an option
      for select patients with osteosarcoma.

PMID- 22131584
TI  - Tussive syncope in a pug with lung-lobe torsion.
AB  - The most common presenting clinical signs of lung-lobe torsion include dyspnea,
      tachypnea, lethargy, and anorexia. Tussive syncope secondary to lung-lobe torsion
      has not been documented. This article describes the presentation, diagnosis,
      management, and outcome of a pug with tussive syncope secondary to lung-lobe
      torsion.

PMID- 22131585
TI  - Repeated pericardiocentesis as palliative treatment for tamponade associated with
      cardiac lymphoma in a Holstein cow.
AB  - Maintaining a good quality of life for cows with cardiac manifestation of
      lymphoma may be valuable, especially in high-producing cows. This report
      describes the medical management of cardiac lymphoma in a cow by means of
      repeated pericardiocentesis. The cow survived for 34 days and was productive.

PMID- 22131586
TI  - Long-term survival of a cow with cervical ectopia cordis.
AB  - This study investigated the long-term survival of a calf with cervical ectopia
      cordis that grew normally, became pregnant, and calved normally. The cow showed
      normal cardiac function and absence of peripheral circulation abnormalities. This
      paper documents antemortem characteristics of the affected cow.

PMID- 22131588
TI  - Transitional cell carcinoma of the urinary bladder in a 14-year-old dog.
AB  - A 14-year-old spayed female poodle-pekinese dog with a history of hematuria was
      tentatively diagnosed with non-radiopaque uroliths or urinary bladder neoplasia
      following temporary resolution of clinical signs after several rounds of
      antibiotic treatments, normal abdominal radiographs and no growth on urine
      culture. Abdominal ultrasound revealed a mass in the trigone area of the urinary
      bladder which was confirmed to be an invasive transitional cell carcinoma by
      histopathology following euthanasia.

PMID- 22131587
TI  - Disorder of sex development (XX male, SRY negative) in a French bulldog.
AB  - A female French bulldog was presented with an enlarged clitoris. Abdominal
      surgery revealed a normal uterus and gonads resembling testes. Histologically,
      the gonads contained seminiferous tubules. The karyotype was XX, and the SRY gene
      was not detected. A diagnosis of XX male, SRY negative disorder of sexual
      development was made.

PMID- 22131589
TI  - The art of private veterinary practice: seeing both sides of the problem.

PMID- 22131590
TI  - Denominational Research Report: Attitudes of Taiwan Catholics Toward Sexual
      Ethics.

PMID- 22131591
TI  - Use of Lichen and Moss in Assessment of Forest Contamination with Heavy Metals in
      Praded and Glacensis Euroregions (Poland and Czech Republic).
AB  - The concentrations of selected metals-Cr, Ni, Cu, Zn, Cd, and Pb-were determined
      in the samples of Hypogymnia physodes lichen and Pleurozium schreberi moss
      collected in Polish and Czech Euroregions Praded and Glacensis. More
      specifically, the samples were collected in Bory Stobrawskie, Bory Niemodlinskie,
      and Kotlina Klodzka (Poland) and in Jeseniki (Czech Republic). The concentration
      of metals in the samples was measured using the atomic absorption spectrometry
      (flame AAS technique and electrothermal atomization AAS technique). The results
      were used to calculate the comparison factor (CF) that quantifies the difference
      in concentration of a given bioavailable analyte * accumulated in lichens and
      mosses: CF = 2 (c(x,lichen) - c(x,moss)) (c(x,lichen) + c(x,moss))(-1). The
      values of CF greater than 0.62 indicate the most probable location of heavy
      metals deposited in the considered area. In this work, the method was used to
      show a significant contribution of urban emissions to the deposition of heavy
      metals in the area of Bory Stobrawskie and in the vicinity of Klodzko City.

PMID- 22131592
TI  - Effects of Seven Fungicides on Non-Target Aquatic Fungi.
AB  - Aquatic risk assessments for fungicides are carried out without information on
      their toxicity to non-target aquatic fungi. This might cause an underestimation
      of the toxic effects to the aquatic fungal community. This study focuses on the
      question whether recently derived concentrations limits for fungicides considered
      to protect populations of primary producers and (in)vertebrates also do protect
      the aquatic fungi. A panel of fungal species and Oomycetes was isolated and
      identified from unpolluted surface waters in the Netherlands. Toxicity tests were
      used to determine effects of seven fungicides with different modes of actions.
      For the triazoles epoxiconazole and tebuconazole, the chronic lowest observable
      effect concentration was lower than the regulatory acceptable concentration based
      on acute HC5 values.

PMID- 22131593
TI  - The future of sleep medicine.

PMID- 22131594
TI  - The lesser of two evils.

PMID- 22131595
TI  - Arterial stiffness: a long sleeper issue?

PMID- 22131596
TI  - Every cloud has a silver lining--treatment of complicated breathing patterns
      during sleep.

PMID- 22131597
TI  - Rehabilitating sleep.

PMID- 22131598
TI  - Bad light affects sleep: "Time and latitude of birth" as determinants of
      children's differential sleep duration across Europe?

PMID- 22131600
TI  - Heritability of insomnia symptoms in youth and their relationship to depression
      and anxiety.
AB  - STUDY OBJECTIVES: Insomnia is a highly prevalent sleep disorder yet little is
      known about the role of genetic factors in its pathophysiology. The aim of this
      study was to examine the relative contributions of genetic and environmental
      factors in explaining variability in insomnia symptoms. DESIGN: Traditional twin
      design. SETTING: Academic medical center. PARTICIPANTS: 1412 twin pairs aged 8-16
      years (48.8% MZ, 47.2% DZ, 4.0% indeterminate). INTERVENTIONS: None. MEASUREMENTS
      AND RESULTS: Ratings of insomnia symptoms, depression, and overanxious disorder
      were made by trained interviewers based on DSM-III-R criteria. ACE models were
      conducted using Mx statistical software. Insomnia symptoms were prevalent in this
      sample based both on parental (6.6%) and youth (19.5%) reports. The overall
      heritability of insomnia symptoms was modest (30.7%), with the remaining variance
      attributed to unique environmental effects. There was no evidence of sex
      differences in the prevalence of insomnia symptoms or in the contribution of
      genetic and environmental effects. In multivariate models, there was support for
      insomnia-specific unique environmental effects over and above overlapping effects
      with depression and overanxious disorder, but no evidence for insomnia-specific
      genetic effects. CONCLUSIONS: Genetic factors play a modest role in the etiology
      of insomnia symptoms in 8-16 year-olds. These effects overlap with the genetics
      of depression and overanxious disorder. Further work is needed to determine which
      genes confer risk for all three disorders.

PMID- 22131599
TI  - The effect of exercise training on obstructive sleep apnea and sleep quality: a
      randomized controlled trial.
AB  - STUDY OBJECTIVES: To evaluate the efficacy of a 12-week exercise training program
      for reducing obstructive sleep apnea (OSA) severity and improving sleep quality,
      and to explore possible mechanisms by which exercise may reduce OSA severity.
      DESIGN: Randomized controlled trial. SETTING: Clinical exercise physiology
      center, sleep laboratory. PARTICIPANTS: Forty-three sedentary and
      overweight/obese adults aged 18-55 years with at least moderate-severity
      untreated OSA (screening apnea-hypopnea index [AHI] >= 15). INTERVENTIONS:
      Participants randomized to exercise training (n = 27) met 4 times/week for 12
      weeks and performed 150 min/week of moderate-intensity aerobic activity, followed
      by resistance training twice/week. Participants randomized to a stretching
      control (n = 16) met twice weekly for 12 weeks to perform low-intensity exercises
      designed to increase whole-body flexibility. MEASUREMENTS AND RESULTS: OSA
      severity was assessed with one night of laboratory polysomnography (PSG) before
      and following the 12-week intervention. Measures of sleep quality included PSG,
      actigraphy (7-10 days), and the Pittsburgh Sleep Quality Index. Compared with
      stretching, exercise resulted in a significant AHI reduction (exercise: 32.2 +/-
      5.6 to 24.6 +/- 4.4, stretching: 24.4 +/- 5.6 to 28.9 +/- 6.4; P < 0.01) as well
      as significant changes in oxygen desaturation index (ODI; P = 0.03) and stage N3
      sleep (P = 0.03). Reductions in AHI and ODI were achieved without a significant
      decrease in body weight. Improvements in actigraphic sleep and subjective sleep
      quality were also noted following exercise compared with stretching. CONCLUSIONS:
      Exercise training had moderate treatment efficacy for the reduction of AHI in
      sedentary overweight/obese adults, which suggests that exercise may be beneficial
      for the management of OSA beyond simply facilitating weight loss. TRIAL
      REGISTRATION: Clinicaltrials.gov identification number NCT00956423.

PMID- 22131601
TI  - MSLT in primary insomnia: stability and relation to nocturnal sleep.
AB  - STUDY OBJECTIVES: To assess the stability of the multiple sleep latency test
      (MSLT) in primary insomnia and its relation to total sleep time. DESIGN:
      Randomized, double-blind, placebo controlled, clinical trial. SETTING: Outpatient
      with sleep laboratory assessments in months 1 and 8 of treatment. PARTICIPANTS:
      Ninety-five primary insomniacs, 32-64 years old and 55 age- and sex-matched
      general population-based, representative controls. INTERVENTIONS: After a
      screening nocturnal polysomnograms (NPSG) and MSLT the following day,
      participants with primary insomnia were randomized to take zolpidem 10 mg (n =
      50) or placebo (n = 45) nightly for 12 months. During months 1 and 8, while
      taking their prescribed treatments, NPSGs and MSLTs the following day were
      conducted. A population-based sample served as controls and received a single
      NPSG followed by MSLT. RESULTS: Mean daily sleep latency on the screening MSLT of
      insomniacs was normally distributed across the full range of MSLT scores and
      significantly higher than those of a population-based representative control
      sample (P < 0.006). The insomniacs with the highest screening MSLTs had the
      shortest screening total sleep times (P < 0.05). The MSLTs of insomniacs during
      treatment in study month 1 were correlated (r = 0.44, P < 0.001) with their month
      8 MSLT. The mean MSLT score of the zolpidem group did not differ from that of the
      placebo group, and the stability within treatment groups also did not differ.
      CONCLUSIONS: These data support the hypothesis that some insomniacs show a
      reliable disorder of hyperarousal with increased wake drive both at night and
      during the day.

PMID- 22131602
TI  - Race and residential socioeconomics as predictors of CPAP adherence.
AB  - STUDY OBJECTIVES: There are few established predictors of CPAP adherence; poor
      adherence limits its effectiveness. We investigated whether race, education
      level, and residential economic status predict CPAP adherence in participants
      enrolled in a trial with standard access to treatment. DESIGN: A multi-center
      randomized trial of home vs. lab-based evaluation and treatment of OSA assessing
      adherence to CPAP at 1 and 3 months. SETTING: Seven AASM-accredited sleep centers
      in 5 U.S. cities. PARTICIPANTS: Subjects with moderate to severe OSA (AHI >= 15
      and Epworth Sleepiness Scale score > 12) who completed follow-up at 1 and/or 3
      months (n = 135). MEASUREMENTS AND RESULTS: Subjects' demographic data were
      collected upon enrollment; CPAP use at 1 and 3 months was assessed at clinic
      follow-up. In unadjusted analyses, CPAP adherence (average minutes per night of
      CPAP use) at 3 months was lower in black subjects and in subjects from lower
      socioeconomic status ZIP codes. In adjusted analyses using multivariate linear
      regression, black race was predictive of CPAP adherence at one month (P = 0.03).
      At 3 months, black race was predictive in analyses only when ZIP code SES was not
      adjusted for. CONCLUSION: Black race and lower socioeconomic residential areas
      are associated with poorer adherence to CPAP in subjects with standardized access
      to care and treatment. Disparities remain despite provision of standardized care
      in a clinical trial setting. Future research is needed to identify barriers to
      adherence and to develop interventions tailored to improve CPAP adherence in at
      risk populations. Portable Monitoring for Diagnosis and Management of Sleep Apnea
      (HomePAP) CLINICAL TRIAL INFORMATION: NIH CLINICAL TRIALS REGISTRY NUMBER:
      NCT00642486. URL: http://clinicaltrials.gov/show/NCT00642486.

PMID- 22131603
TI  - Habitual short sleep impacts frontal switch mechanism in attention to novelty.
AB  - STUDY OBJECTIVES: Reduced time in bed relative to biological sleep need is
      common. The impact of habitual short sleep on auditory attention has not been
      studied to date. In the current study, we utilized novelty oddball tasks to
      evaluate the effect of habitual short sleep on brain function underlying
      attention control processes measured by the mismatch negativity (MMN, index of
      pre-attentive stage), P3a (attention-dependent), and P3b (memory-dependent) event
      related brain potentials (ERPs). An extended time in bed in a separate study was
      used to evaluate the possible reversal of the impairments of these processes in
      habitual short sleepers. METHODS: Ten self-defined short sleepers (total sleep
      time [TST] <= 6 h) and 9 normal-sleeping subjects with TST 7-8 h, participated.
      ERPs were recorded via a 64-channel EEG system. Two test conditions: "ignore" and
      "attend" were implemented. The ERPs were analyzed and compared between groups on
      the 2 task conditions and frontal/central/parietal electrodes by 3-factor ANOVA.
      Sleep diary data were compared between groups by t-test. Sleep was recorded by
      the Zeo sleep monitoring system for a week in both habitual and extended sleep
      conditions at home. RESULTS: The main findings of the present study show that
      short sleeping individuals had deficiency in activity of the MMN and P3a brain
      responses over frontal areas compared to normal-sleeping subjects. The P3b
      amplitude was increased over frontal areas and decreased over parietal with
      respect to the control group. Extension of time in bed for one week increased TST
      (from 5.7 h to 7.4 h), and concomitantly MMN amplitude increased from -0.1 MUV up
      to -1.25 MUV over frontal areas. CONCLUSIONS: Reduced time in bed is associated
      with deficiency of the neuronal process associated with change detection, which
      may recover after one week of sleep extension, whereas attention-dependent neural
      processes do not normalize after this period of time in habitually short sleeping
      individuals and may require longer recovery periods.

PMID- 22131604
TI  - A randomized controlled trial of cognitive-behavior therapy plus bright light
      therapy for adolescent delayed sleep phase disorder.
AB  - OBJECTIVE: To evaluate cognitive-behavior therapy plus bright light therapy (CBT
      plus BLT) for adolescents diagnosed with delayed sleep phase disorder (DSPD).
      DESIGN: Randomized controlled trial of CBT plus BLT vs. waitlist (WL) control
      with comparisons at pre- and post-treatment. There was 6-month follow-up for the
      CBT plus BLT group only. SETTING: Flinders University Child & Adolescent Sleep
      Clinic, Adelaide, South Australia. PATIENTS: 49 adolescents (mean age 14.6 +/-
      1.0 y, 53% males) diagnosed with DSPD; mean chronicity 4 y 8 months; 16% not
      attending school. Eighteen percent of adolescents dropped out of the study (CBT
      plus BLT: N = 23 vs. WL: N = 17). INTERVENTIONS: CBT plus BLT consisted of 6
      individual sessions, including morning bright light therapy to advance
      adolescents' circadian rhythms, and cognitive restructuring and sleep education
      to target associated insomnia and sleep hygiene. MEASUREMENTS AND RESULTS: DSPD
      diagnosis was performed via a clinical interview and 7-day sleep diary.
      Measurements at each time-point included online sleep diaries and scales
      measuring sleepiness, fatigue, and depression symptoms. Compared to WL, moderate
      to-large improvements (d = 0.65-1.24) were found at post-treatment for CBT plus
      BLT adolescents, including reduced sleep latency, earlier sleep onset and rise
      times, total sleep time (school nights), wake after sleep onset, sleepiness, and
      fatigue. At 6-month follow-up (N = 15), small-to-large improvements (d = 0.24
      1.53) continued for CBT plus BLT adolescents, with effects found for all
      measures. Significantly fewer adolescents receiving CBT plus BLT met DPSD
      criteria at post-treatment (WL = 82% vs. CBT plus BLT = 13%, P < 0.0001), yet 13%
      still met DSPD criteria at the 6-month follow-up. CONCLUSIONS: CBT plus BLT for
      adolescent DSPD is effective for improving multiple sleep and daytime impairments
      in the immediate and long-term. Studies evaluating the treatment effectiveness of
      each treatment component are needed. CLINICAL TRIAL INFORMATION: Australia-New
      Zealand Trials Registry Number: ACTRN12610001041044.

PMID- 22131605
TI  - Relation between self-reported sleep duration and arterial stiffness: a cross
      sectional study of middle-aged Japanese civil servants.
AB  - OBJECTIVES: The aim of this study is to examine the relationship between self
      reported sleep duration and arterial stiffness in a large-scale Japanese study.
      DESIGN: Cross-sectional study. SETTING: Sapporo City, Hokkaido, Japan.
      PARTICIPANTS: Local government employees aged 35-62 years, who underwent annual
      health checkups from April 2003 to March 2004. After excluding those with
      incomplete data, data from 4,268 employees (males: 3,410) participants were
      analyzed. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Brachial-ankle pulse-wave
      velocity (baPWV) was investigated as an indicator of arterial stiffness. We used
      a self-administered questionnaire, which included items on daily sleep duration,
      lifestyle factors, and occupational factors. Sleep duration was classified into 5
      categories; " <= 5 h," "6 h," "7 h," "8 h," and " >= 9 h." Results of multiple
      linear regression analysis after fully adjusting the model revealed that subjects
      with >= 9 h of daily sleep had significantly elevated baPWV values compared with
      the reference group with 7 h of sleep. Stratified analyses by sex showed that
      there was a significant association among male subjects only. CONCLUSIONS: Daily
      sleep duration >= 9 h was found to be associated with elevated values of baPWV.
      This suggests that there is an association between long sleep duration and
      arterial stiffness.

PMID- 22131606
TI  - Continuous positive airway pressure in severe obstructive sleep apnea reduces
      pain sensitivity.
AB  - STUDY OBJECTIVE: To evaluate effects of CPAP on pain sensitivity in severe OSA
      patients. DESIGN: Within-subject treatment study. SETTING: Hospital-based sleep
      disorders center. PATIENTS: Twelve severe OSA patients (7 men, 5 women), 50.2 +/-
      12.5 years, with no pain. INTERVENTIONS: The morning after a diagnostic nocturnal
      polysomnogram (NPSG), patients underwent a training session of finger withdrawal
      latency (FWL) testing to a radiant heat stimulus, a validated human behavioral
      model of thermal nociception. Baseline FWL in seconds was obtained after the
      training session. CPAP pressure was titrated on a second night in the laboratory.
      Two nights after titration, patients returned to sleep in the laboratory on CPAP.
      FWL was tested in the morning after awakening, after 6-8 wks of CPAP use, and
      finally (within 6-8 weeks) after 2 nights of discontinuation of CPAP. Mean FWL in
      seconds (sec) was compared using MANOVAs with nights as the within subject
      variable. RESULTS: Apnea-hypopnea index (AHI) decreased from 50.9 +/- 14.5 to 1.4
      +/- 1.0 with CPAP, and sleep continuity improved. In parallel, FWL increased
      significantly from a mean baseline of 9.8 +/- 1.3 sec to 13.7 +/- 5.1 sec (P =
      0.01) and with continued CPAP use (5.1 +/- 2.3 h nightly) for 6-8 weeks FWL
      remained elevated (21.1 +/- 16.2 sec). After the 2-night CPAP discontinuation,
      apnea/hypopneas returned and sleep was fragmented (AHI = 32.6 +/- 19.8). FWL
      decreased to 11.6 +/- 5.9 sec relative to intermediate-term CPAP use (P = 0.03).
      CONCLUSION: CPAP treatment reduces pain sensitivity in OSA patients. Future
      studies will focus on patients with OSA and chronic pain and identify mediating
      mechanisms.

PMID- 22131607
TI  - The performance of two automatic servo-ventilation devices in the treatment of
      central sleep apnea.
AB  - INTRODUCTION: This study was conducted to evaluate the therapeutic performance of
      a new auto Servo Ventilation device (Philips Respironics autoSV Advanced) for the
      treatment of complex central sleep apnea (CompSA). The features of autoSV
      Advanced include an automatic expiratory pressure (EPAP) adjustment, an advanced
      algorithm for distinguishing open versus obstructed airway apnea, a modified auto
      backup rate which is proportional to subject's baseline breathing rate, and a
      variable inspiratory support. Our primary aim was to compare the performance of
      the advanced servo-ventilator (BiPAP autoSV Advanced) with conventional servo
      ventilator (BiPAP autoSV) in treating central sleep apnea (CSA). STUDY DESIGN: A
      prospective, multicenter, randomized, controlled trial. SETTING: Five sleep
      laboratories in the United States. PARTICIPANTS: Thirty-seven participants were
      included. MEASUREMENTS AND RESULTS: All subjects had full night polysomnography
      (PSG) followed by a second night continuous positive airway pressure (CPAP)
      titration. All had a central apnea index >= 5 per hour of sleep on CPAP. Subjects
      were randomly assigned to 2 full-night PSGs while treated with either the
      previously marketed autoSV, or the new autoSV Advanced device. The 2 randomized
      sleep studies were blindly scored centrally. Across the 4 nights (PSG, CPAP,
      autoSV, and autoSV Advanced), the mean +/- 1 SD apnea hypopnea indices were 53 +/
      23, 35 +/- 20, 10 +/- 10, and 6 +/- 6, respectively; indices for CSA were 16 +/-
      19, 19 +/- 18, 3 +/- 4, and 0.6 +/- 1. AutoSV Advanced was more effective than
      other modes in correcting sleep related breathing disorders. CONCLUSIONS: BiPAP
      autoSV Advanced was more effective than conventional BiPAP autoSV in the
      treatment of sleep disordered breathing in patients with CSA.

PMID- 22131608
TI  - Higher frontal EEG synchronization in young women with major depression: a marker
      for increased homeostatic sleep pressure?
AB  - STUDY OBJECTIVES: Major depressive disorder (MDD) is often associated with
      disturbances in circadian and/or sleep-wake dependent processes, which both
      regulate daytime energy and sleepiness levels. DESIGN: Analysis of continuous
      electroencephalographic (EEG) recordings during 40 h of extended wakefulness
      under constant routine conditions. Artifact-free EEG samples derived from 12
      locations were subjected to spectral analysis. Additionally, half-hourly ratings
      of subjective tension and sleepiness levels and salivary melatonin measurements
      were collected. SETTING: Centre for Chronobiology, Psychiatric Hospitals of the
      University of Basel, Switzerland. PARTICIPANTS: Eight young healthy women and 8
      young untreated women with MDD. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: MDD
      women exhibited higher frontal low-frequency (FLA) EEG activity (0.5-5.0 Hz)
      during extended wakefulness than controls, particularly during the night.
      Enhanced FLA was paralleled by higher levels of subjective sleepiness and
      tension. In MDD women, overall FLA levels correlated positively with depression
      scores. The timing of melatonin onset did not significantly differ between the
      two groups, but the nocturnal secretion of salivary melatonin was significantly
      attenuated in MDD women. CONCLUSIONS: Our data imply that young women with MDD
      live on a higher homeostatic sleep pressure level, as indexed by enhanced FLA
      during wakefulness. Its positive correlation with depression scores indicates a
      possible functional relationship. High FLA could reflect a use-dependent
      phenomenon in depression (enhanced cognitive rumination or tension) and/or an
      attenuated circadian arousal signal.

PMID- 22131609
TI  - Correlating subjective and objective sleepiness: revisiting the association using
      survival analysis.
AB  - STUDY OBJECTIVES: The Epworth Sleepiness Scale (ESS) and multiple sleep latency
      test (MSLT) are the most commonly used measures of subjective and objective
      sleepiness, respectively. The strength of the association between these measures
      as well as the optimal ESS threshold that indicates objective sleepiness remains
      a topic of significant interest in the clinical and research arenas. The current
      investigation sought to: (a) examine the association between the ESS and the
      average sleep latency from the MSLT using the techniques of survival analysis;
      (b) determine whether specific patient factors influence the association; (c)
      examine the utility of each ESS question; and (d) identify the optimal ESS
      threshold that indicates objective sleepiness. DESIGN: Cross-sectional study.
      PATIENTS AND SETTINGS: Patients (N = 675) referred for polysomnography and MSLT.
      MEASUREMENTS AND RESULTS: Using techniques of survival analysis, a significant
      association was noted between the ESS score and the average sleep latency. The
      adjusted hazard ratios for sleep onset during the MSLT for the ESS quartiles were
      1.00 (ESS < 9), 1.32 (ESS: 10-13), 1.85 (ESS: 14-17), and 2.53 (ESS >= 18),
      respectively. The association was independent of several patient factors and was
      distinct for the 4 naps. Furthermore, most of the ESS questions were individually
      predictive of the average sleep latency except the tendency to doze off when
      lying down to rest in the afternoon, which was only predictive in patients with
      less than a college education. Finally, an ESS score >= 13 optimally predicted an
      average sleep latency < 8 minutes. CONCLUSIONS: In contrast to previous reports,
      the association between the ESS and the average sleep latency is clearly apparent
      when the data are analyzed by survival analysis, and most of the ESS questions
      are predictive of objective sleepiness. An ESS score >= 13 most effectively
      predicts objective sleepiness, which is higher than what has typically been used
      in clinical practice. Given the ease of administering the ESS, it represents a
      relatively simple and cost-effective method for identifying individuals at risk
      for daytime sleepiness.

PMID- 22131610
TI  - Poor self-reported sleep quality predicts mortality within one year of inpatient
      post-acute rehabilitation among older adults.
AB  - STUDY OBJECTIVE: To evaluate the association between self-reported sleep quality
      among older adults during inpatient post-acute rehabilitation and one-year
      survival. DESIGN: Prospective, observational cohort study. SETTING: Two inpatient
      post-acute rehabilitation sites (one community and one Veterans Administration).
      PARTICIPANTS: Older patients (aged >= 65 years, n = 245) admitted for inpatient
      post-acute rehabilitation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Within
      one year of post-acute rehabilitation, 57 participants (23%) were deceased. Cox
      proportional hazards models showed that worse Pittsburgh Sleep Quality Index
      (PSQI) total scores during the post-acute care stay were associated with
      increased mortality risk when controlling for amount of rehabilitation therapy
      received, comorbidities, and cognitive functioning (Hazard ratio [95% CI] = 1.11
      [1.02-1.20]). Actigraphically estimated sleep was unrelated to mortality risk.
      CONCLUSIONS: Poorer self-reported sleep quality, but not objectively estimated
      sleep parameters, during post-acute rehabilitation was associated with shorter
      survival among older adults. This suggests self-reported poor sleep may be an
      important and potentially modifiable risk factor for negative outcomes in these
      vulnerable older adults. Studies of interventions to improve sleep quality during
      inpatient rehabilitation should therefore be undertaken, and the long-term health
      benefits of improved sleep should be explored.

PMID- 22131611
TI  - The association of fatigue with depression and insomnia in HIV-seropositive
      patients: a pilot study.
AB  - OBJECTIVE: Fatigue is a pervasive symptom associated with HIV, resulting in
      significant functioning impairment; but little is known about its etiology or
      treatment. In patients with primary insomnia, data have shown improvement in
      fatigue following successful treatment of insomnia. However, little is known
      about the role of insomnia in patients with fatigue in HIV. This manuscript seeks
      to test the hypothesis that insomnia severity is correlated with increased
      fatigue in HIV-seropositive patients. METHODS: Fifty-seven ambulatory HIV
      seropositive patients, aged 18-60 years, with a DSM-IV-TR diagnosis of insomnia,
      were administered the Insomnia Severity Index (ISI), Piper Fatigue Scale (PFS),
      Hospital Anxiety and Depression scale, and Hamilton Depression Rating Scale (HAM
      D). Their most recent CD4 count and time since diagnosis of HIV were recorded.
      Regression analysis was carried out with PFS as the dependent variable. RESULTS:
      A higher ISI score correlated with higher PFS score, (R2 = 0.1713, P = 0.0042).
      Overall depression severity was not significantly correlated with PFS score,
      except in the most severely depressed subgroup, in which the HADS depression
      score was the strongest predictor of PFS (R2 = 0.182, P = 0.0009). In
      participants without depression, ISI accounted for most of the variance in
      fatigue (R2 = 0.6035, P = 0.0011). CONCLUSIONS: Greater insomnia severity is
      associated with greater fatigue severity in HIV seropositive patients. Depression
      may contribute to both fatigue and insomnia. In the absence of depression, the
      treatment of insomnia may emerge as a treatment strategy to help alleviate
      fatigue. Further studies are needed to confirm these data. CLINICAL TRIAL
      INFORMATION: Clinical Trials.Gov: The Treatment of Insomnia in Patients with HIV
      Disease. Registry Number: NCT00465972. URL:
      http://www.clinicaltrials.gov/ct2/show/NCT00465972?term = HIV+insomnia&rank = 1.

PMID- 22131612
TI  - Stimulus-induced, sleep-bound, focal seizures: a case report.
AB  - STUDY OBJECTIVES: In nocturnal frontal lobe epilepsy (NFLE), seizures occur
      almost exclusively during NREM sleep. Why precisely these seizures are sleep
      bound remains unknown. Studies of patients with nonlesional familial forms of
      NFLE have suggested the arousal system may play a major role in their
      pathogenesis. We report the case of a patient with pharmaco-resistant, probably
      cryptogenic form of non-familial NFLE and strictly sleep-bound seizures that
      could be elicited by alerting stimuli and were associated with ictal bilateral
      thalamic and right orbital-insular hyperperfusion on SPECT imaging. DESIGN: Case
      report. SETTING: University Hospital Zurich. PATIENTS OR PARTICIPANTS: One
      patient with pharmaco-resistant epilepsy. CONCLUSION: This case shows that the
      arousal system plays a fundamental role also in cryptogenic non-familial forms of
      NFLE.

PMID- 22131614
TI  - Gender Role Traits Among Individuals with Social Anxiety Disorder.
AB  - The present study investigated differences between individuals with and without
      social anxiety disorder (SAD) in instrumentality and expressiveness, personality
      traits traditionally linked to the male and female gender roles, respectively.
      Based on evolutionary and self-discrepancy theories, it was hypothesized that
      individuals with SAD would score lower on instrumentality and report a
      discrepancy between their perceived and ideal level of instrumentality compared
      to control participants. Sixty-four patients with SAD and 31 non-anxious control
      participants completed a battery of questionnaires, including ratings of their
      perceived and ideal gender role attributes and current psychosocial distress.
      Results supported the hypotheses, and provided initial evidence that a
      discrepancy between perceived and ideal instrumentality may be linked to social
      anxiety severity, depression and lower quality of life. No differences were
      detected between groups in expressiveness. The present findings suggest that
      individuals with SAD perceive themselves to be deficient in instrumentality. They
      also suggest that increasing instrumentality among individuals with SAD may be
      beneficial for treatment.

PMID- 22131613
TI  - The Impact of Subjective Work Control, Job Strain and Work-Family Conflict on
      Fertility Intentions: a European Comparison.
AB  - The link between employment and fertility is often only examined by focussing on
      women's labour market status or the impact of part- versus full-time employment.
      This study introduces a new explanation by extending research to examine how
      women's subjective perceptions of control or autonomy over work, job strain and
      work-family conflict influence fertility intentions. National-level measures of
      childcare enrolment under the age of three and the occurrence of part-time work
      are also included to examine their relation to fertility intentions and their
      interplay with perceptions of work. Using data from 23 countries from the 2004/5
      European Social Survey (ESS), multilevel logistic regression models of fertility
      intentions are estimated separately for women without children and women with one
      child. Women with higher levels of work control are significantly more likely to
      intend to have a second child. Higher levels of job strain (time pressure)
      significantly lower fertility intentions for mothers in contexts where childcare
      availability is low. The prevalence of part-time work amongst the female work
      force significantly predicts the intention to become a mother but has different
      effects for women who work part-time themselves compared with full-time
      employees.

PMID- 22131615
TI  - Substitute of Animals in Drug Research: An Approach Towards Fulfillment of 4R's.
AB  - The preclinical studies for drug screening involve the use of animals which is
      very time consuming and expensive and at times leads to suffering of the used
      organism. Animal right activists around the world are increasingly opposing the
      use of animals. This has forced the researchers to find ways to not only decrease
      the time involved in drug screening procedures but also decrease the number of
      animals used and also increase the humane care of animals. To fulfill this goal a
      number of new in vitro techniques have been devised which are called
      'Alternatives' or 'Substitutes' for use of animals in research involving drugs.
      These 'Alternatives' are defined as the adjuncts which help to decrease the use
      as well as the number of animals in biomedical research. Russell and Burch have
      defined these alternatives by three R's - Reduction, Refinement and Replacement.
      These alternative strategies include physico-chemical methods and techniques
      utilizing tissue culture, microbiological system, stem cells, DNA chips, micro
      fluidics, computer analysis models, epidemiological surveys and plant-tissue
      based materials. The advantages of these alternatives include the decrease in the
      number of animals used, ability to obtain the results quickly, reduction in the
      costs and flexibility to control the variables of the experiment. However these
      techniques are not glittering gold and have their own shortcomings. The
      disadvantages include the lack of an appropriate alternative to study the whole
      animal's metabolic response, inability to study transplant models and
      idiosyncratic responses and inability to study the body's handling of drugs and
      its subsequent metabolites. None-the-less these aalternative methods to certain
      extent help to reduce the number of animals required for research. But such
      alternatives cannot eliminate the need for animals in research completely. Even
      though no animal model is a complete set of replica for a process within a human
      body, the intact animal does provide a better model of the complex interaction of
      the physiological processes.

PMID- 22131617
TI  - Introduction to fiber optics: Sensors for biomedical applications.
AB  - The paper focuses on the introduction of fiber optics, a fusion of science and
      engineering and describes the materials generally used for its construction along
      with the procedure used to design the fibers. It gives an idea of the materials
      used for the construction along with the pros and cons associated with them and
      various factors governing the emission of ultraviolet, infrared or visible
      radiations. The central core revolves around the applications of optical fibers
      in the medical and biomedical field and extending the use of the same in
      pharmaceutical industry as probes in quality control and dosage form analysis.

PMID- 22131616
TI  - Von Willebrand disease: an overview.
AB  - Most commonly inherited bleeding disorder, first described in Aland Islands by
      Erik von Willebrand. It occurs as a result of decrease in plasma levels or defect
      in von Willebrand factor which is a large multimeric glycoprotein. Monomers of
      this glycoprotein undergo N-glycosylation to form dimers which get arranged to
      give multimers. Binding with plasma proteins (especially factor VIII) is the main
      function of von Willebrand factor. The disease is of two forms: Inherited and
      acquired forms. Inherited forms are of three major types. They are type 1, type
      2, and type 3; in which type 2 is sub-divided into 2A, 2B, 2M, 2N. Type 1 is more
      prevalent than all other types. Mucocutaneous bleeding is mild in type 1 whereas
      it is mild to moderate in types 2A, 2B, and 2M. Type 2N has similar symptoms of
      haemophilia. The pathophysiology of each type depends on the qualitative or
      quantitative defects in von Willebrand factor. The diagnosis is based on von
      Willebrand factor antigen, von Willebrand factor activity assay, FVIII coagulant
      activity and some other additional tests. Results should be analyzed within the
      context of blood group. von Willebrand factor multimer analysis is essential for
      typing and sub typing the disease. The management of the disease involves
      replacement therapy, non-replacement therapy and other therapies that include
      antifibrinolytics and topical agents.

PMID- 22131618
TI  - Development and Validation of a Reversed-phase HPLC Method for Simultaneous
      Determination of Aspirin, Atorvastatin Calcium and Clopidogrel Bisulphate in
      Capsules.
AB  - A simple, accurate, rapid and precise isocratic reversed-phase high-performance
      liquid chromatographic method has been developed and validated for simultaneous
      determination of aspirin, atorvastatin calcium and clopidogrel bisulphate in
      capsules. The chromatographic separation was carried out on an Inertsil ODS
      analytical column (150*4.6 mm; 5 MUm) with a mixture of acetonitrile:phosphate
      buffer pH 3.0 adjusted with o-phosphoric acid (50:50, v/v) as mobile phase; at a
      flow rate of 1.2 ml/min. UV detection was performed at 235 nm. The retention
      times were 1.89, 6.6 and 19.8 min. for aspirin, atorvastatin calcium and
      clopidogrel bisulphate, respectively. Calibration plots were linear (r(2)>0.998)
      over the concentration range 5-30 MUg/ml for atorvastatin calcium and 30-105
      MUg/ml for aspirin and clopidogrel bisulphate. The method was validated for
      accuracy, precision, specificity, linearity, and sensitivity. The proposed method
      was successfully used for quantitative analysis of capsules. No interference from
      any component of pharmaceutical dosage form was observed. Validation studies
      revealed that method is specific, rapid, reliable, and reproducible. The high
      recovery and low relative standard deviation confirm the suitability of the
      method for routine determination of aspirin, atorvastatin calcium and clopidogrel
      bisulphate in bulk drug and capsule dosage form.

PMID- 22131619
TI  - Preparation and In Vitro Evaluation of a Stomach Specific Drug Delivery System
      based on Superporous Hydrogel Composite.
AB  - This study discusses efforts made to design drug-delivery system based on
      superporous hydrogel composite for sustained delivery of ranitidine
      hydrochloride. The characterization studies involve measurement of apparent
      density, porosity, swelling studies, mechanical strength studies, and scanning
      electron microscopy. Scanning electron microscopic images clearly showed the
      formation of interconnected pores, capillary channels, and the cross-linked
      sodium carboxymethylcellulose molecules around the peripheries of pores. The
      prepared system floated and delivered the ranitidine hydrochloride for about 17
      h. The release profile of ranitidine hydrochloride was studies by changing the
      retardant polymer in the system. To ascertain the drug release kinetics, the
      dissolution profiles were fitted to different mathematical models that include
      zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas, Weibull, and
      Hopfenberg models. The in vitro dissolution from system was explained by
      Korsmeyer-Peppas model. The diffusion exponent values in Korsmeyer-Peppas model
      range between 0.48+/-0.01 and 0.70+/-0.01, which appears to indicate an anomalous
      non-Fickian transport. It is concluded that the proposed mechanically stable
      floating drug-delivery system based on superporous hydrogel composite containing
      sodium carboxymethylcellulose as a composite material is promising for stomach
      specific delivery of ranitidine hydrochloride.

PMID- 22131620
TI  - Prediction of Malnutrition Using Modified Subjective Global Assessment-dialysis
      Malnutrition Score in Patients on Hemodialysis.
AB  - Malnutrition is widely prevalent among patients on hemodialysis. Malnutrition can
      be estimated using a fully quantitative scoring system Subjective Global
      Assessment-Dialysis Malnutrition Score which is simple, reliable and dynamic. The
      primary objective of the study was to assess the severity of malnutrition in
      patients with end stage renal disease and undergoing hemodialysis in a tertiary
      care teaching hospital in Chennai, using Subjective Global Asses sment-Dialysis
      Malnutrition Score and correlate it with standard indicators of malnutrition like
      anthropometric and biochemical parameters of the study population by Pearson's
      correlation. Anthropometric assessment included height, body weight, triceps skin
      fold thickness, mid arm circumference, mid arm muscle circumference % and
      biochemical parameters included serum albumin, transferrin, ferritin, total
      protein, total cholesterol, blood urea nitrogen and creatinine. Based on the
      scores, of the 66 patients, 91% were moderately malnourished. There was a
      significant negative correlation between modified Subjective Global Assessment
      Dialysis Malnutrition Score and anthropometric measures such as triceps skin fold
      thickness, mid arm circumference, mid arm muscle circumference; biochemical
      markers such as albumin, transferrin and ferritin. The data obtained from this
      study confirm that a high degree of malnutrition was prevalent in patients on
      hemodialysis, as shown by anthropometric assessment, biochemical markers of
      malnutrition and Subjective Global Assessment-Dialysis Malnutrition Score.
      Nutritional status as determined by Subjective Global Assessment-Dialysis
      Malnutrition Score is a useful and reliable index for identifying patients at
      risk for malnutrition and it correlates well with anthropometric and biochemical
      assessment. may be integrated in regular assessment of malnutrition in patients
      on maintenance hemodialysis.

PMID- 22131621
TI  - Stability-indicating HPLC Method for Simultaneous Determination of Terbutaline
      Sulphate, Bromhexine Hydrochloride and Guaifenesin.
AB  - The aim of the present study was the development and subsequent validation of a
      simple, precise and stability-indicating reversed phase HPLC method for the
      simultaneous determination of guaifenesin, terbutaline sulphate and bromhexine
      hydrochloride in the presence of their potential impurities in a single run. The
      photolytic as well as hydrolytic impurities were detected as 3,5-dihydroxybenzoic
      acid, 3,5-dihydroxybenzaldehyde, 1-(3,5-dihydroxyphenyl)-2-[(1,1-dimethylethyl)
      amino]-ethanone from terbutaline, 2-methoxyphenol and an unknown impurity
      identified as (2RS)-3-(2-hydroxyphenoxy)-propane-1,2-diol from guaifenesin. The
      chromatographic separation of all the three active components and their
      impurities was achieved on Wakosil II column, using phosphate buffer (pH 3.0) and
      acetonitrile as mobile phase which was delivered initially in the ratio of 80:20
      (v/v) for 18 min, then changed to 60:40 (v/v) for next 12 min, and finally
      equilibrated back to 80:20 (v/v) for 10 min. Other HPLC parameters were: Flow
      rate at 1.0 ml/min, detection wavelengths 248 and 280 nm, injection volume 10
      MUl. The calibration graphs plotted with five concentrations of each component
      were linear with a regression coefficient R(2) >0.9999. The limit of detection
      and limit of quantitation were estimated for all the five impurities. The
      established method was then validated for linearity, precision, accuracy, and
      specificity and demonstrated to be applicable to the determination of the active
      ingredients in commercial and model cough syrup. No interference from the
      formulation excipients was observed. These results suggest that this LC method
      can be used for the determination of multiple active ingredients and their
      impurities in a cough and cold syrup.

PMID- 22131622
TI  - Formulation and Evaluation of Long Circulating Liposomal Amphotericin B: A Scinti
      kinetic Study using Tc in BALB/C Mice.
AB  - In the present study, we formulated long circulating liposomes for amphotericin B
      and characterized them. The formulation was optimized using 2(3) factorial
      designs. Pegylated liposomal formulation showed favorable results with reference
      to particle size (247.33+/-9.60 nm), percent entrapment efficiency (94.55+/
      3.34%). TEM studies revealed that the liposomes were essentially spherical,
      hollow, and appeared like powder puff structures. From DSC study it was concluded
      that the pegylated formulation containing Amp B showed better stability and
      membrane integrity of the formulation. During the stability studies the
      formulation was found to be stable. When subjected to gamma scintigraphy kinetic
      tracer studies the formulation showed longer residence time in the blood in
      BALB/C mice.

PMID- 22131623
TI  - Standardization of sulaharan yoga: an ayurvedic tablet formulation.
AB  - Quality assurance of herbal products may be ensured by proper quality control of
      the herbal ingredients and by means of good manufacturing practice. We have
      developed a simple scheme for the standardization and authentication of Sulaharan
      Yoga a poly herbal formulation. Sulaharan Yoga was prepared as per Ayurvedic
      Formulary of India. In-house and marketed preparation has been standardized on
      the basis of organoleptic characters, physical characteristics and physico
      chemical properties. The set parameters were found to be sufficient to
      standardize the Sulaharan Yoga and can be used as reference standards for the
      quality control/ quality assurance study.

PMID- 22131624
TI  - Simultaneous spectrophotometric estimation of nitazoxanide and ofloxacin in
      tablets.
AB  - Two simple, accurate and precise spectrophotometric methods have been developed
      for simultaneous determination of nitazoxanide and ofloxacin in tablets. Method I
      is Q-absorbance ratio method which involves Q-absorbance at isobestic point
      (306.25 nm) and max (347.5 nm) of nitazoxanide, while method II is two wavelength
      method, where 244.6 nm and 273.0 nm were selected as 1 and 2 for determination of
      nitazoxanide and 294.3 nm and 388.1 nm were selected as 3 and 4 for determination
      of ofloxacin. Both drugs obeyed the Beer's law in the concentration range 2-30
      MUg/ml,correlation coefficient (r(2)<1). Both methods were validated
      statistically and recovery studies were carried out to confirm the accuracy.
      Commercial tablet formulation was successfully analyzed using the developed
      methods.

PMID- 22131625
TI  - Visible spectrophotometric method for the determination of aripiprazole in
      tablets.
AB  - A simple, accurate and economic spectrophotometric method for the determination
      of aripiprazole in tablet formulation is proposed. In the present method acidic
      solution of the aripiprazole formed colored ion-association complexes with
      bromocresol green, soluble in chloroform. Yellowish orange chromogen showed
      lambda(max) at 414 nm and obeyed Beer's law in the concentration range of 10-60
      MUg/ml. Statistical analysis and recovery studies validated the method. The
      proposed method is rapid, precise and accurate and can be applied for the routine
      estimation of aripiprazole in the laboratory.

PMID- 22131626
TI  - Leucocyte variation, an insight of host defenses during hymenolepiasis and
      restoration with praziquantel.
AB  - Haematological studies in helminthiasis reveal drastic alterations in the white
      blood cells (leucocytes), and its various components like neutrophils,
      lymphocytes, monocytes and eosinophils. The use of proper anthelmintic agent,
      restores normalcy in the infected host. These variations during helminth
      infections reflect the host defense status in combating the parasitic attack. The
      present study involves the evaluation of these total and differential
      haematological alterations, induced in the laboratory mouse Mus musculus,
      infested with the intestinal helminth, Hymenolepis nana (dwarf tapeworm), and
      treated with the praziquantel, using an automatic Coulter Counter.

PMID- 22131627
TI  - Isolation and characterization of impurities present in 8-chlorotheophylline.
AB  - A simple isocratic reversed phase high performance liquid chromatography was used
      to separate three impurities present in the sample of 8-chlorotheophylline. LC-MS
      was used for the characterization of impurities. Based on mass spectral data, the
      structures of these impurities were characterized as 3,7-dihydro-1,3-dimethyl-1H
      purine-2,6-dione (impurity I), 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
      (impurity II) and isomer of 8-chloro-1,3-dimethyl-2,6(3H,1H)-purinedione
      (impurity III).

PMID- 22131628
TI  - RP-HPLC Method for Simultaneous Estimation of Nitazoxanide and Ofloxacin in
      Tablets.
AB  - A reverse phase high performance liquid chromatography method was developed for
      simultaneous estimation of nitazoxanide and ofloxacin in tablet formulation. The
      separation and quantification was achieved by Hiq Sil C(18)V Size 4.6 mm O (*)250
      mm column in isocratic mode, with mobile phase consisting of acetonitrile
      methanol-0.4 M citric acid, (60:30:10, v/v/v). Citric acid used to stabilize
      nitazoxanide and ofloxacin in mobile phase. The mobile phase was pumped at a rate
      of 0.6 ml/min and the detection was carried out at 304 nm. The retention time of
      ofloxacin and nitazoxanide was found to be 3.122 and 5.902 min, respectively. The
      method was validated for linearity, accuracy, and precision. Linearity for
      ofloxacin and nitazoxanide were in the range 2-36 MUg/ml and 5-90 MUg/ml,
      respectively. The developed method was found to be accurate, precise and
      selective for simultaneous estimation of ofloxacin and nitazoxanide in tablets.

PMID- 22131629
TI  - Computer Aided Prediction of Biological Activity Spectra: Study of Correlation
      between Predicted and Observed Activities for Coumarin-4-Acetic Acids.
AB  - Coumarin-4-acetic acids have been synthesized from various phenols and citric
      acid under Pechmann cyclisation conditions. All the compounds have been evaluated
      for antiinflammatory and analgesic activity in acute models. Compounds have also
      been evaluated for their ulcerogenic potential. Using the computer program,
      prediction of activity spectra for substances, prediction results and their
      Pharma Expert software, we have found a correlation between the observed and
      predicted antiinflammatory activity.

PMID- 22131630
TI  - Antimicrobial Activity of Medicated Soaps Commonly Used By Dar es Salaam
      Residents in Tanzania.
AB  - An in vitro evaluation of the anti-microbial activity of medicated soaps was
      conducted using ditch-plate and hand washing techniques. Strains of reference
      microbes namely Candida albicans (ATCC90028), Staphylococcus aureus (ATCC25923),
      Pseudomonas aureginosa (ATCC27853) and Escherichia coli (ATCC25922) were tested
      at three different soaps' concentrations (1.0, 4.0 and 8.0 mg/ml). A total of 16
      medicated soaps were assayed for their antimicrobial efficacy. Of these, 13 were
      medicated and 3 non-medicated soaps, which served as control. Ciprofloxacin and
      ketaconazole were employed as positive controls. Label disclosure for the soaps'
      ingredients and other relevant information were absorbed. The most common
      antimicrobial active ingredients were triclosan, trichloroxylenol and
      trichlorocarbanilide. ANOVA for means of zones of inhibition revealed variability
      of antimicrobial activity among the medicated soaps. Positive correlation
      (r=0.318; P<0.01) between zones of inhibition and soaps' concentrations was
      evidenced. Hand washing frequencies positively correlated with microbial counts.
      Roberts((r)) soap exhibited the largest zone of inhibition (34 mm) on S. aureus.
      Candida albicans was the least susceptible microbe. Regency((r)) and Dalan((r))
      exhibited the least zone of inhibition on the tested bacteria. Protex((r)),
      Roberts((r)), Family((r)) and Protector((r)) were equally effective (P<0.01)
      against S. aureus. In conclusion, majority of the assayed medicated soaps have
      satisfactory antibacterial activity; though lack antifungal effect with exception
      of Linda((r)) liquid soap. The hand washing technique has proved to be
      inappropriate for evaluation of soaps' antimicrobial efficacy due to presence of
      the skin microflora.

PMID- 22131631
TI  - A comparative study of the anthelmintic potential of cleome viscosa L. And cleome
      burmanni w. And a.
AB  - Methanol, aqueous and chloroform extracts of Cleome viscosa and Cleome burmanni
      were tested for anthelmintic potential against the Indian earthworm Pheritima
      posthuma. Different concentrations of the extracts ranging from 50-2000 MUg/ml
      were tested and results expressed as time required for paralysis and death of the
      worms. Piperazine citrate was used as a reference standard and DMSO (1%) as the
      negative control. The methanol extracts of Cleome viscosa and Cleome burmanni
      exhibited significant anthelmintic activity. Methanol extract of Cleome viscosa
      at a concentration of 2000 MUg/ml was detected to be the most effective treatment
      dose. Thin layer chromatography of methanol extracts of both plants revealed the
      presence of terpenoids.

PMID- 22131632
TI  - Synthesis, Antiinflammatory and Antimicrobial Activity of Some New 1-(3-Phenyl
      3,4-Dihydro-2H-1,3-Benzoxazin-6-yl)-Ethanone Derivatives.
AB  - Synthesis of title compounds (4a-j) was carried out by following aminomethylation
      Mannich reaction. Test compounds were effective in inhibiting edema induced by
      carrageenan. The percent inhibition obseved was in the range of 25-83.3%.
      Compound (4c, e, h and j) were also tested for analgesic effect and showed
      percent protection ranging between 57-65%. All the synthesized compounds were
      active against E. coli and S. aureus but only compounds (4 b, c, e, i and j) were
      active against B. subtilis. All these compound were also found active against A.
      niger. Compound 4j was the most active compound with 83.3% inhibition of edema,
      65.35% percent protection and inhibited all the three bacterial strains.

PMID- 22131633
TI  - Determination of anthelmintic activity of the leaf and bark extract of tamarindus
      indica linn.
AB  - The aim of the present study was to evaluate the anthelmintic activity of
      ethanolic and aqueous extract of leaves and bark of Tamarindus indica Linn using
      Pheretima posthuma and Tubifex tubifex as test worms. The time of paralysis and
      time of death were studied and the activity was compared with piperazine citrate
      as reference standard. The alcohol and aqueous extract of bark of Tamarindus
      indica exhibited significant anthelmintic activity as evidenced by decreased
      paralyzing time and death time. The results thus support the use of Tamarindus
      indica as an anthelmintic agent.

PMID- 22131634
TI  - Determination of Alkyl Methanesulfonates in Doxazosin Mesylate by Gas
      Chromatography-mass Spectrometer.
AB  - High sensitive rapid gas chromatography-mass spectrometry method for the
      determination of four carcinogenic alkyl methanesulfonates viz. methyl
      methanesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate and n-butyl
      methanesulfonate in doxazosin mesylate has been presented by using selective ion
      monitoring mode. The optimum separation was achieved between methyl
      methanesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate and n-butyl
      methanesulfonate on a DB-5 (30 m*0.32 mm*1.0 MUm) capillary column under
      programming temperature. Acetonitrile, water and ammonia (90:9:1 v/v/v) mixture
      was used as diluent. Various factors involved in the gas chromatography-mass
      spectrometry method development are also presented. This method was validated as
      per International Conference on Harmonization guidelines. The limit of
      quantitation of methyl methanesulfonate, ethyl methanesulfonate, isopropyl
      methanesulfonate and n-butyl methanesulfonate is 6 ppm with respect to 30 mg/ml
      of doxazosin mesylate.

PMID- 22131635
TI  - Study on the antibacterial potential of physalis minima linn.
AB  - Physalis minima is an important medicinal plant of Indian System of Medicine.
      This plant is reported for its diuretic, laxative and antiinflammatory
      activities. However, the plant is not well scrutinized for its antimicrobial
      potential. The major chemical constituents reported from the plant are phenolics
      and alkaloids, which suggest that the plant may turn out to be a potent
      antiinfective agent. The aim of the study was to find out the antibacterial
      potential of mature berries of P. minima using streak plate, well diffusion,
      determination of minimum inhibitory concentration and bioautographic methods
      against a battery of Gram positive and Gram negative bacterial strains. Results
      of the study showed that methanol and chloroform extracts of P. minima exhibited
      potent inhibitory activity against all the bacterial strains tested. Minimum
      inhibitory concentration found out was 100 MUg in both the extracts.
      Bioautography assay showed polar compounds present in the crude extract are
      responsible for the antimicrobial action.

PMID- 22131636
TI  - Synthesis and pharmacological activities of some new 3-substituted-4-amino-5
      mercapto-1,2,4-triazoles.
AB  - In this study, various 3-beta-[(N-benzenesulphonyl/tosyl)-4-(un) substituted
      anilino]ethyl-4-amino-5-mercapto-4(H)-1,2,4-triazoles (5a-f), with biologically
      active 'sulphonamide' moiety as the side chain have been prepared. The structures
      of the newly synthesised compounds have been established on the basis of their
      spectral data and elemental analysis. All the compounds were evaluated for
      antimicrobial activities against Escherichia coli, Bacillus cirroflagellosus,
      Aspergillus niger and Colletotrichum capsici. Most of the compounds investigated
      exhibited significant antifungal activity against Colletotrichum capsici, even
      greater than fluconazole, the standard used. Only two compounds 3f (59%) and 5e
      (67%), have shown moderate antituberculosis activity. All the triazoles exhibited
      moderate degree of antiinflammatory activity and least ulcerogenecity. Most of
      the compounds have shown significant analgesic activity (81.02-120.72%) in
      comparison with aspirin (49.39%). In the MES method, only compound 3e exhibited a
      protection of 66.66%, whereas others exhibited minimum protection of (33.33%).

PMID- 22131637
TI  - Determination of Doxazosin Mesylate in Tablets by RP-HPLC.
AB  - A simple, precise and rapid RP-HPLC method was developed for the determination of
      doxazosin mesylate in pharmaceutical formulations. The method was carried out on
      a Chromolith RP-C(18) column using a mixture of potassium phosphate buffer and
      methanol (40:60 v/v) and detection was done at 251 nm. The linearity range was 1
      5 MUg/ml. The retention time of the drug was 3.8 min. The LOD and LOQ were found
      to be 0.1 MUg/ml and 0.5 MUg/ml, respectively.

PMID- 22131638
TI  - Treatment of word-finding deficits in fluent aphasia through the manipulation of
      spatial attention: Preliminary findings.
AB  - BACKGROUND: Attention, the processing of one source of information to the
      exclusion of others, is important for most cognitive processes, including
      language. Evidence suggests not only that dysfunctional attention mechanisms
      contribute to language deficits after stroke, but also that orienting attention
      to a patient's ipsilesional hemispace recruits attention mechanisms in the intact
      hemisphere and improves language functions in some persons with aphasia.  AIMS:
      The aim of the current research was to offer proof of concept for the strategy of
      improving picture-naming performance in fluent aphasia by moving stimuli into the
      left hemispace. It was hypothesised that repeated orientation of attention to the
      ipsilesional hemispace during picture naming would lead to improved naming
      accuracy for participants with fluent aphasia.  METHODS #ENTITYSTARTX00026;
      PROCEDURES: Three participants with stable fluent aphasia received daily
      treatment sessions that consisted of naming simple line drawings presented 45
      degrees to the left of body midline on a computer monitor. Naming probes were
      administered before initiation of the treatment protocol to establish a baseline,
      and before each treatment session to measure change during treatment. The C
      statistic was used to establish the stability of baseline performance and to
      determine whether the slope of the treatment phases differed significantly from
      the slope of the baseline.  OUTCOMES #ENTITYSTARTX00026; RESULTS: Two of the
      three participants showed significant improvement over baseline performance in
      the percent correct of naming probes. One participant showed no improvement over
      baseline accuracy.  CONCLUSIONS: Results suggest that engaging right-hemisphere
      attention mechanisms may improve naming accuracy in some people with fluent
      aphasia. Findings justify further investigation of this treatment in a larger
      controlled study.

PMID- 22131639
TI  - Comparison of phase structures and surface free energy values for the coatings
      synthesised from linear polyurethanes and from waterborne polyurethane
      cationomers.
AB  - WAXS, DSC and AFM methods were employed to compare phase structures of the
      coatings obtained from waterborne polyurethane cationomers which had been
      synthesised in the reaction of some diisocyanates (MDI, IPDI, TDI and HDI) with
      polyoxyethylene glycols (M = 600 and 2,000) and butane1,4-diol or N-methyl- or N
      butyldiethanolamine and 2,2,3,3-tetrafluoro-1,4-butanediol. The structures were
      also analysed of the coatings derived from linear polyurethanes which had been
      synthesised on the basis of similar raw materials. Better rigidity was found for
      generally amorphous cationomer coats. Changes were discussed in the surface free
      energy (SFE) values and in their components, as calculated independently with the
      use of the van Oss-Good and Owens-Wendt methods. Polyurethane coats turned out
      more hydrophobic as compared to cationomer ones. In both coat types, fluorine
      incorporated into cationomers contributed to lower SFE values: from 50 down to
      about 30 mJ/m(2).

PMID- 22131640
TI  - Microanatomy of the trophosome region of Paracatenula cf. polyhymnia (Catenulida,
      Platyhelminthes) and its intracellular symbionts.
AB  - Marine catenulid platyhelminths of the genus Paracatenula lack mouth, pharynx and
      gut. They live in a symbiosis with intracellular bacteria which are restricted to
      the body region posterior to the brain. The symbiont-housing cells
      (bacteriocytes) collectively form the trophosome tissue, which functionally
      replaces the digestive tract. It constitutes the largest part of the body and is
      the most important synapomorphy of this group. While some other features of the
      Paracatenula anatomy have already been analyzed, an in-depth analysis of the
      trophosome region was missing. Here, we identify and characterize the composition
      of the trophosome and its surrounding tissue by analyzing series of ultra-thin
      cross-sections of the species Paracatenula cf. polyhymnia. For the first time, a
      protonephridium is detected in a Paracatenula species, but it is morphologically
      reduced and most likely not functional. Cells containing needle-like inclusions
      in the reference species Paracatenula polyhymnia Sterrer and Rieger, 1974 were
      thought to be sperm, and the inclusions interpreted as the sperm nucleus. Our
      analysis of similar cells and their inclusions by EDX and Raman microspectroscopy
      documents an inorganic spicule consisting of a unique magnesium-phosphate
      compound. Furthermore, we identify the neoblast stem cells located underneath the
      epidermis. Except for the modifications due to the symbiotic lifestyle and the
      enigmatic spicule cells, the organization of Paracatenula cf. polyhymnia conforms
      to that of the Catenulida in all studied aspects. Therefore, this species
      represents an excellent model system for further studies of host adaptation to an
      obligate symbiotic lifestyle. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s00435-011-0135-y) contains supplementary
      material, which is available to authorized users.

PMID- 22131641
TI  - Dextral and sinistral Amphidromus inversus (Gastropoda: Pulmonata: Camaenidae)
      produce dextral sperm.
AB  - Coiling direction in pulmonate gastropods is determined by a single gene via a
      maternal effect, which causes cytoskeletal dynamics in the early embryo of
      dextral gastropods to be the mirror image of the same in sinistral ones. We note
      that pulmonate gastropod spermatids also go through a helical twisting during
      their maturation. Moreover, we suspect that the coiling direction of the helical
      elements of the spermatozoa may affect their behaviour in the female reproductive
      tract, giving rise to the possibility that sperm chirality plays a role in the
      maintenance of whole-body chiral dimorphism in the tropical arboreal gastropod
      Amphidromus inversus (Muller, 1774). For these reasons, we investigated whether
      there is a relationship between a gastropod's body chirality and the chirality of
      the spermatozoa it produces. We found that spermatozoa in A. inversus are always
      dextrally coiled, regardless of the coiling direction of the animal itself.
      However, a partial review of the literature on sperm morphology in the Pulmonata
      revealed that chiral dimorphism does exist in certain species, apparently without
      any relationship with the coiling direction of the body. Though our study shows
      that body and sperm chirality follows independent developmental pathways, it
      gives rise to several questions that may be relevant to the understanding of the
      chirality of spermatid ultrastructure and spermatozoan motility and sexual
      selection.

PMID- 22131642
TI  - Comparative morphology of the male genitalia of Aphididae (Insecta, Hemiptera):
      part 1.
AB  - The present study provides new data concerning the morphology of the male
      genitalia of Aphididae and unifies their nomenclature. The structure of the male
      genitalia of 31 species from 26 genera of Aphididae was studied with light and
      scanning electron microscopy. In the studied species, the genitalia of males
      consist of a phallus composed of the sclerotized basal part with its articulation
      and a membranous apical part-an aedeagus. Laterally of the phallus, there is a
      pair of setose parameres. The shape of the aedeagus, the shape and length of the
      sclerotized basal part and its articulation as well as the variability of
      parameres in their form and the number of setae are recognized as important
      systematic signs of the genitalia. These characters are considered in conjunction
      with the phylogenetic relationships among the studied taxa.

PMID- 22131643
TI  - Rural-Urban Migration and Experience of Childhood Abuse in the Young Thai
      Population.
AB  - Evidence suggests that certain migrant populations are at increased risk of
      abusive behaviors. It is unclear whether this may also apply to Thai rural-urban
      migrants, who may experience higher levels of psychosocial adversities than the
      population at large. The study aims to examine the association between migration
      status and the history of childhood sexual, physical, and emotional abuse among
      young Thai people in an urban community. A population-based cross-sectional
      survey was conducted in Northern Bangkok on a representative sample of 1052 young
      residents, aged 16-25 years. Data were obtained concerning: 1) exposures
      migration (defined as an occasion when a young person, born in a more rural area
      moves for the first time into Greater Bangkok) and age at migration. 2) outcomes
      child abuse experiences were assessed with an anonymous self report adapted from
      the Conflict Tactics Scales (CTS). There were 8.4%. 16.6% and 56.0% reporting
      sexual, physical, and emotional abuse, respectively. Forty six percent of
      adolescents had migrated from rural areas to Bangkok, mostly independently at the
      age of 15 or after to seek work. Although there were trends towards higher
      prevalences of the three categories of abuse among early migrants, who moved to
      Bangkok before the age of 15, being early migrants was independently associated
      with experiences of physical abuse (OR 1.9 95%CI 1.1-3.2) and emotional abuse (OR
      2.0, 95%CI 1.3-3.0) only. Our results suggest that rural-urban migration at an
      early age may place children at higher risk of physical and emotional abuse. This
      may have policy implications for the prevention of childhood abuse particularly
      among young people on the move.

PMID- 22131644
TI  - Light respiration in Chlorella sorokiniana.
AB  - Respiration and photosynthesis are two important processes in microalgal growth
      that occur simultaneously in the light. To know the rates of both processes, at
      least one of them has to be measured. To be able to measure the rate of light
      respiration of Chlorella sorokiniana, the measurement of oxygen uptake must be
      fast, preferably in the order of minutes. We measured the immediate post
      illumination respiratory O(2) uptake rate (OUR) in situ, using fiber-optic oxygen
      microsensors, and a small and simple extension of the cultivation system. This
      method enables rapid and frequent measurements without disturbing the cultivation
      and growth of the microalgae. Two batch experiments were performed with C.
      sorokiniana in a short light-path photobioreactor, and the OUR was measured at
      different time points. The net oxygen production rate (net OPR) was measured
      online. Adding the OUR and net OPR gives the gross oxygen production rate (gross
      OPR), which is a measure for the oxygen evolution by photosynthesis. The gross
      OPR was 35-40% higher than the net OPR for both experiments. The respiration rate
      is known to be related to the growth rate, and it is suggested that faster algal
      growth leads to a higher energy (ATP) requirement, and as such, respiratory
      activity increases. This hypothesis is supported by our results, as the specific
      OUR is highest in the beginning of the batch culture when the specific growth
      rate is highest. In addition, the specific OUR decreases toward the end of the
      experiments until it reaches a stable value of around 0.3 mmol O(2) h(-1) g(-1).
      This value for the specific OUR is equal to the maintenance requirement of C.
      sorokiniana as determined in an independent study of (Zijffers et al. 2010 (in
      press)). This suggests that respiration could fulfill the maintenance
      requirements of the microalgal cells.

PMID- 22131645
TI  - Phase toxicity of dodecane on the microalga Dunaliella salina.
AB  - In the so-called milking process of Dunaliella salina carotenoids are extracted
      and simultaneously produced by the culture, whilst the biomass concentration
      remains constant. Different theories exist about the extraction mechanisms
      although none have been proven yet. In this research, direct contact between
      dodecane and cells during the extraction process was studied microscopically and
      effects of direct contact were determined during in situ extraction experiments.
      Our results showed that water-solvent interphase contact resulted in cell death.
      This cell death and consequent cell rupture resulted in the release and
      concomitant extraction of the carotenoids. Furthermore, it has been suggested to
      add a small amount of dichloromethane to the biocompatible dodecane to create an
      organic phase with more extraction capacity. Our results showed that the addition
      of dichloromethane resulted in increased cell death and consequently the
      extraction rate increased. The improved solubility of carotenoids in an organic
      phase with dichloromethane did not significantly increase the extraction rate.

PMID- 22131646
TI  - Role of oxidants in interstitial lung diseases: pneumoconioses, constrictive
      bronchiolitis, and chronic tropical pulmonary eosinophilia.
AB  - Oxidants such as superoxide anion, hydrogen peroxide, and myeloperoxidase from
      activated inflammatory cells in the lower respiratory tract contribute to
      inflammation and injury. Etiologic agents include inorganic particulates such as
      asbestos, silica, or coal mine dust or mixtures of inorganic dust and combustion
      materials found in World Trade Center dust and smoke. These etiologic agents are
      phagocytosed by alveolar macrophages or bronchial epithelial cells and release
      chemotactic factors that recruit inflammatory cells to the lung. Chemotactic
      factors attract and activate neutrophils, eosinophils, mast cells, and
      lymphocytes and further activate macrophages to release more oxidants. Inorganic
      dusts target alveolar macrophages, World Trade Center dust targets bronchial
      epithelial cells, and eosinophils characterize tropical pulmonary eosinophilia
      (TPE) caused by filarial organisms. The technique of bronchoalveolar lavage in
      humans has recovered alveolar macrophages (AMs) in dust diseases and eosinophils
      in TPE that release increased amounts of oxidants in vitro. Interestingly, TPE
      has massively increased eosinophils in the acute form and after treatment can
      still have ongoing eosinophilic inflammation. A course of prednisone for one week
      can reduce the oxidant burden and attendant inflammation and may be a strategy to
      prevent chronic TPE and interstitial lung disease.

PMID- 22131648
TI  - Editorial: "ten commandments" of safe and optimum thyroid surgery.

PMID- 22131647
TI  - Emerging role of PPAR-beta/delta in inflammatory process associated to
      experimental periodontitis.
AB  - The aim of the present study was to evaluate the contribution of peroxisome
      proliferator-activated receptor (PPAR-beta/delta) in animal model of
      periodontitis. Male Sprague-Dawley rats were lightly anaesthetized with
      pentobarbitone (35 mg/kg). Sterile, 2-0 black braided silk thread was placed
      around the cervix of the lower left first molar and knotted medially. Animals
      received GW0742 (0.3 mg/kg, 10% DMSO, i.p. after the ligature placement and daily
      for eight days). At day 8, the gingivomucosal tissue encircling the mandibular
      first molar was removed. One the eighth day after placement of the ligature, we
      evaluated (1) NF-kappaB expression, (2) cytokines expression, (3) iNOS
      expression, (5) the nitration of tyrosine, (6) apoptosis, and (8) the degree of
      gingivomucosal tissues injury. Administration of GW0742 significantly decreased
      all of the parameters of inflammation as described above. Taken together, these
      results demonstrate that GW0742 exerts an anti-inflammatory role during
      experimental periodontitis and is able to ameliorate the tissue damage.

PMID- 22131649
TI  - Lymphoepithelial cyst of the pancreas: a rare case report and review of
      literature.
AB  - Lymphoepithelial cysts are rare pancreatic lesions of undetermined pathogenesis.
      The literature on this entity is limited to case reports or small series. We
      describe a case of 66 year male, incidentally diagnosed as lymphoepithelial cyst
      of pancreas that was managed by enucleation. This is the first case report of
      lymphoepithelial cyst from India. An extensive Medline search was carried out for
      lymphoepithelial cyst of pancreas. Till date less than 100 cases were identified
      in available literature. All these cases (including our case) were analyzed. This
      entity has uniform and distinctive clinicopathological features. About half of
      the reported cases were asymptomatic with most of the lesions diagnosed
      incidentally. Majority of patients presents with non-specific symptoms making
      preoperative diagnosis difficult. Lymphoepithelial cyst of the pancreas is a rare
      benign lesion, which is difficult to diagnose preoperatively. High index of
      suspicion and preoperative fine needle aspiration cytology may help in making
      diagnosis and avoiding surgery in asymptomatic patients. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s12262-010-0152-y)
      contains supplementary material, which is available to authorized users.

PMID- 22131650
TI  - Breast tuberculosis- clinical spectrum and management.
AB  - Objective of the study was to report the clinical spectrum, investigative profile
      and management of breast tuberculosis patients attending a tertiary care
      hospital. Breast tuberculosis is an uncommon form of tuberculosis. Knowledge of
      its varied clinical presentation and diagnostic modalities help in diagnosing
      this easily treatable disease. Retrospective data of 63 consecutive patients with
      breast tuberculosis was analyzed and information regarding demographic details,
      clinical presentation, cytology, histopathology and management was noted. Breast
      tuberculosis is essentially a disease of females (98.41%). 49.20% patients were
      below 30 years of age and 68.25% were from rural areas. Incidence of tubercular
      mastitis increases with parity (71.42% with p > 2). Commonest presentation was
      with painless lump (73%). Nodulocaseous tubercular disease was found in 74.60%
      patients whereas, 6.3% were of disseminated variety. Primary focus was detected
      in lungs in 11.1% patients, while 46.03% presented with loco-regional lymph
      nodes. FNAC was found to be a sensitive tool of diagnosis in 74.60% patients;
      however 25.39% cases were diagnosed with biopsy. ATT remained mainstay of
      treatment with surgical intervention as and when required. Breast tuberculosis
      despite being uncommon is not rare. Although diagnosis is not difficult but one
      should know where to suspect. Once confirmed treatment outcome is often
      rewarding.

PMID- 22131651
TI  - Diagnosis and management of atypical mycobacterial infection after laparoscopic
      surgery.
AB  - Atypical mycobacterial infections at the laparoscopic port site are a frequent
      problem encountered in patients undergoing laparoscopic surgery. In this study we
      concentrate on the clinical diagnosis, management and prevention of this problem.
      In this series we assess 19 patients presenting with port hole infections after
      laparoscopic surgery and were treated with a combination of oral clarithromycin
      and ciprofloxacin. Seven patients who had persistent nodules were given
      injections of amikacin directly into the infection foci along with standard oral
      therapy. Most of the patients treated with standard oral therapy for 28 days
      showed recovery. The patients with persistent nodules 4 weeks after completion of
      therapy were treated with injections of amikacin directly into the nodule which
      lead to resolution of symptoms. For prevention of infection, proper sterilization
      and storage of instruments is recommended. Laparoscopic port hole infections is a
      preventable problem and can also be treated by nonsurgical method.

PMID- 22131652
TI  - Complete rectal prolapse in adults: clinical and functional results of delorme
      procedure combined with postanal repair.
AB  - This study has been performed at the Department of General Surgery, Zagazig
      University Hospital and King Saud Hospital, Oniza, KSAduring the period from
      November 1998 to September 2008.Twentyadult patients (6 males and 14 females with
      a mean age of 55 years) with complete rectal prolapse were eligible for the
      study, Where Delorme's procedure and postanal repairwere combined. All patients
      presented with complete rectal prolapse at least 5 cm in length. The associated
      disorders included constipation (4 patients, 20%), variable degrees of
      incontinence (15 patients, 75%). Only one patient had no associated functional
      problems. The median follow up period was 65 months. There was no mortality and
      immediate postoperative complications developed in 4 patients (20%). Recurrence
      of the prolapse occurred in two patient. Eleven patients (73.3%) (11/17) with
      faecal incontinence showed postoperative improvement and 4 patients failed to
      improve. The 4 patients presented with constipation were all improved
      postoperatively. We conclude that the combination of Delorme's procedure and
      postanal repair in the treatment of complete rectal prolapse in adults is a safe
      procedure that corrects the anatomical defects and improves the functional
      outcome. We recommend use of this method in the treatment of complete rectal
      prolapse especially in the elderly who are complaining of faecal incontinence.

PMID- 22131653
TI  - Study of the Radical vs. Conservative Surgical Treatment of the Hepatic Hydatid
      Cyst: A 10-Year Experience.
AB  - The hepatic hydatid cyst is a major health problem in endemic areas. Surgery is
      still the best choice for the treatment of hydatid cyst of the liver. There is
      controversy regarding efficacy of radical versus conservative surgical
      approaches. In this study, we aimed to evaluate the two surgical methods in
      patients treated for the hepatic hydatid cyst. This is a retrospective review of
      the medical records of 135 patients who underwent surgery for the hepatic hydatid
      cyst from 1993 to 2003. Surgery comprised conservative methods (evacuation of the
      cyst content and excision of the inner cyst layers) and radical methods (total
      excision of the cyst and removal of its outer layer). One hundred thirty five
      patients underwent liver surgery. Conservative surgery was performed for 71
      (53%), whereas, the remaining 64 patients (47%) underwent radical surgery. Local
      recurrence rate of the cysts was lower in the radical versus conservative surgery
      group and the mean length of hospital stay was shorter in the radical surgery
      group. Radical surgery of the hepatic hydatid cyst may be the preferred treatment
      because of its low rate of local recurrence, as well as short hospital stay.

PMID- 22131654
TI  - Nutritional assessment of patients after pylorus-preserving gastrectomy for early
      gastric cancer.
AB  - The aim of this study was to evaluate the nutritional advantages of pylorus
      preserving gastrectomy (PPG) in comparison with distal gastrectomy with Billroth
      I anastomosis (DG) in early gastric cancer (EGC). Between 2005 and 2007, 24
      patients underwent PPG and 30 underwent DG. Subjective global assessment,
      objective data assessment, and endoscopic findings of the remnant stomach were
      compared between the two groups. Two years after surgery, the patients' body
      weights recovered to 97% in PPG, but they continued to decrease in DG.
      Postoperative blood lymphocyte counts remained low in DG, but recovered to
      preoperative levels 6 months after surgery in PPG. Food residue in the gastric
      remnant was frequently observed in PPG (71.4%) than in DG (15.8%, P = 0.001). In
      nutritional aspect, PPG may be a more ideal operation than DG. However, food
      residue in the gastric remnant should be considered in PPG. ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12262
      010-0167-4) contains supplementary material, which is available to authorized
      users.

PMID- 22131655
TI  - Endovenous ablation of saphenofemoral insufficiency: analysis of 100 patients
      using RF closure fast technique.
AB  - Chronic venous insufficiency is a common problem leading to varicose veins of
      lower limbs which was traditionally being treated with ligation and stripping.
      Endovenous ablation is an attractive alternative minimally invasive technique to
      treat such patients. We analysed the results of 100 consecutive patients treated
      with Radiofrequency based endovenous ablation using Closure Fast Catheter.
      Retrospective analysis of 100 consecutive patients with chronic venous
      insufficiency treated at our institution was done. All patients were classified
      pre and post procedure based on clinical, etiologic, anatomic and
      pathophyslogical classification, Venous clinical severity and Venous disablitity
      scores alongwith color doppler examination with follow up done at 2 weeks, 3
      months and one year for any disease recurrence or residual symptoms. 97 of the
      100 patients treated at 3 months and at 1 year showed good reduction of venous
      clinical severity and Venous disability scores to 0. Doppler showed complete
      closure of saphenofemoral junction and long saphenous vein at 2 weeks with no
      recanalisation at one year. No thrombus formation was observed. Minor
      complications like ecchymosis was seen in 9 patients and thrombophlebitis in 4
      patients. Endovenous ablation using radiofrequency with Closure Fast technique
      showed improved short and long term results in patients with venous insufficiency
      with 100% closure seen on doppler studies along with lesser complications and no
      thrombus formation due shortened procedure time and improved catheter design.

PMID- 22131656
TI  - A novel morbidity prediction model for head and neck oncosurgery.
AB  - The purpose of the study was to construct and validate a risk model to predict
      morbidity in head and neck oncosurgeries. Potential risk factors of 300
      surgically treated head and neck cancer patients like age, sex, tumor site, TNM
      stage, duration of surgery, adjunctive treatment, comorbidities and alcohol and
      tobacco usage were analyzed. Postoperative complications were noted. We developed
      a logistic model to predict the probability of patients developing morbidity
      based on the statistically significant variables-duration of surgery,
      preoperative radiation and hypertension. The validity of the test was assessed by
      the c-index which were 0.79 (95% C.I 0.71-0.87) for the study set (250 patients)
      and 0.86(95% C.I 0.73-0.90) for the test set (50 patients). The correlation of
      observed to expected morbidity was 0.709 (P < 0.0001). We validated a risk model
      and constructed a simple chart that provides us an assessment of the risk of a
      patient of developing morbidity.

PMID- 22131657
TI  - Skin glue improves outcome after excision and primary closure of sacrococcygeal
      pilonidal disease.
AB  - Evaluating the effect of Histoacryl on the outcome and recurrence rate after
      excision and primary closure of sacrococcygeal pilonidal disease. Forty patients
      with sacrococcygeal pilonidal sinus were randomly divided into 2 equal groups
      through computer randomization program. Group I was operated by complete excision
      of sinus with wound closure using Histoacryl. Group II was operated with primary
      wound closure by interrupted inverting sutures. Mean operative time was 31.5 +/-
      5.6 minutes in group I and 35.9 +/- 5.1 minutes in group II. Mean healing time
      was 13.4 +/- 2.7 days in group I and 18.0 +/- 8.9 days in group II. Wound
      infection occurred in 2 patients (10%) in Group II. Delayed wound healing
      occurred in 3 patients (15%) in group I and 4 patients (20%) in group II.
      Recurrence occurred in 1 patient (5%) in group I and 3 patients (15%) in group
      II. Histoacryl improves outcome (significantly decreases operative and healing
      times and increases patient satisfaction score, insignificantly decreases rates
      of complications and recurrence) after excision and primary closure of
      sacrococcygeal pilonidal disease.

PMID- 22131658
TI  - Comparative evaluation of adhesions to intraperitoneally placed fixation
      materials: a laparoscopic study in rats: adhesions to fixation materials.
AB  - After laparoscopic ventral hernia repair, the nature of the adhesions to fixation
      materials or to mesh had not been clarified. We examined adhesion formation
      specific to the fixation material in rats. We designed an experimental
      laparoscopy setup, and placed four intraperitoneal fixation materials on the
      peritoneum of rats without a mesh graft. Another group of researchers documented
      the incidence and intensity of postoperative adhesion formation. The adhesion
      scores for the nickel-titanium anchor were significantly greater than those for
      polylactic acid (p = 0.004), a titanium tacker (p < 0.0001), and fibrin glue (p <
      0.0001). No adhesions occurred in the fibrin glue group. Fibrin glue is the
      preferred fixation material because it produced no postoperative adhesions. The
      nickel-titanium anchor produced heavy adhesions but may be applicable for
      recurrent hernia cases and in patients with thin abdominal walls.

PMID- 22131659
TI  - Two rare cases of intrahepatic subcapsular hematoma after laparoscopic
      cholecystectomy.
AB  - The appearance of subcapsular liver hematoma after a laparoscopic cholecystectomy
      (LC) is an infrequent complication and seldom studied. Some cases have been
      connected to ketorolac given during surgery and after surgery. Other described
      causes are : hemangiomas or small iatrogenic lesions that could be aggravated by
      administration of ketorolac. Coagulation dysfunction like circulating heparin as
      seen in hemathological diseases is cause of bleeding after aggressive procedures.
      We describe two cases of subcapsular liver hematoma after LC, both of them have
      been given intravenous ketorolac and one of them had multiple myeloma. We discuss
      the causes and treatment of it.

PMID- 22131660
TI  - Thoracic outlet syndrome caused by hydatid cyst of the first rib-rare but
      important.
AB  - Hydatid cysts are usually located in the liver and lungs. Skeletal echinococcosis
      is relatively rare and that of the rib is exceptional. Less than 50 cases of
      costal echinococcosis have been reported in the literature so far. To our
      knowledge, only one case report of thoracic outlet syndrome due to echinococcal
      cyst in the first rib was described in 1995. Accurate pre-operative diagnosis is
      important but may be challenging in some cases. Reported here is a case of
      echinococcosis of the first rib in a young adult who was presented with thoracic
      outlet syndrome. Plain chest radiograph, CT scan and MRI were performed. The
      imaging features were suggestive of a solitary aneurysmal bone cyst and the
      differential diagnosis included echinococcosis of the first rib. The lesion was
      completely resected and the histopathological examination confirmed the diagnosis
      of echinococcosis.

PMID- 22131661
TI  - Preoperative prediction difficult laparoscopic cholecystectomy.

PMID- 22131662
TI  - Speech therapy with obturator.
AB  - Rehabilitation of speech is tantamount to closure of defect in cases with
      velopharyngeal insufficiency. Often the importance of speech therapy is sidelined
      during the fabrication of obturators. Usually the speech part is taken up only at
      a later stage and is relegated entirely to a speech therapist without the active
      involvement of the prosthodontist. The article suggests a protocol for speech
      therapy in such cases to be done in unison with a prosthodontist.

PMID- 22131663
TI  - Survey on Bolton's Tooth Size Analysis as Applied to Artificial Teeth.
AB  - The presence of proportionate teeth size in either arch is a must to obtain an
      ideal occlusion with good alignment, ideal overjet, ideal overbite and Class I
      molar relationship. The above facts made us think and to know if this proportion
      between maxillary and mandibular teeth existed in artificial teeth also? Hence, a
      survey is undertaken to study the tooth size relation in commercially available
      artificial teeth. From the results of the present study it was concluded that the
      anterior and the overall ratios are slightly varied when compared to the standard
      Bolton's ratios. On comparison the difference between the study ratios and the
      standard Bolton's ratios were not statistically significant.

PMID- 22131664
TI  - A cephalometric study to determine the plane of occlusion in completely
      edentulous patients: part I.
AB  - To determine the relationship between the plane of occlusion and the Camper's
      line (ala-tragus line). Lateral cephalograms of 105 dentulous subjects were
      obtained after outlining the tragus and the base of the ala of the nose with
      radiopaque markers. Tracings of the cephalograms were done and the relationship
      between the plane of occlusion and the Camper's line (ala-tragus line) was noted.
      The most common tragal reference as a posterior landmark for determination of
      plane of occlusion was found to be below inferior (in 30.48% of subjects), and
      inferior (in 24.76% of subjects). The least common tragal reference was found to
      be above superior (in 3.82% of subjects) followed by superior of tragus and the
      point between superior and middle of the tragus (in 6.66% of subjects). The
      tragal reference in this study population was more towards the inferior of the
      tragus, with most of the times being below the inferior border. Therefore, the
      orientation of the plane of occlusion using the superior of tragus as a posterior
      landmark (according to the widely accepted definition of Camper's line) may be
      considered to be questionable. Further, the use of the tragus as a posterior
      landmark for the orientation of the plane of occlusion may be questioned on the
      basis of the findings of this study.

PMID- 22131665
TI  - Effect of surface treatment on the flexural strength of denture base resin and
      tensile strength of autopolymerizing silicone based denture liner bonded to
      denture base resin: an in vitro study.
AB  - Silicone based denture liners are superior to acrylic based denture liners but it
      has a problem of failure of adhesion with the denture base. To evaluate the
      effect on the tensile bond strength of silicone based liner and flexural strength
      of denture base resin when the latter is treated with different chemical etchants
      prior to the application of the resilient liner. Rectangular specimens of heat
      cured PMMA (65 * 10 * 3.3 mm(3)) for flexural strength and (10 * 10 * 40 mm(3))
      for tensile strength were fabricated and divided into four subgroups each. One
      subgroup of each type acted as a control and the rest were subjected to surface
      treatment with acetone for 30 s, MMA monomer for 180 s, methylene chloride for 15
      s, respectively. Silicone based denture liner was processed between 2 PMMA
      specimens (10 * 10 * 40 mm(3)) in the space provided by a spacer, thermocycled
      (5(-)55 degrees C) for 500 cycles and then their tensile strength measurements
      and flexural strength measurements were done. 180 s of MMA monomer treatment was
      found to be most effective in improving the bonding between the liner and denture
      base resin as well as producing the lowest decrease in flexural strength of
      denture base resin. Chemical treatment of denture base resin improves the bond
      strength of denture liner but it also decreases the flexural strength of denture
      base. So careful selection of chemical etchant should be done so as to produce
      minimum decrease in flexural strength of denture base resin.

PMID- 22131666
TI  - An Evaluation of Fracture Strength of Zirconium Oxide Posts Fabricated Using CAD
      CAM Technology Compared with Prefabricated Glass Fibre Posts.
AB  - Post and core therapy is regarded as the treatment of choice for restoring
      severely damaged endodontically treated teeth. Critical control of endodontic
      materials in the coronal third of the canal and pulp chamber is essential in
      order to maintain its colour and translucency. In addition to this, the
      duplication of the optical characteristics of an intact tooth, including shade
      translucency and fluorescence is often made difficult by the use of metal
      infrastructures. As a result of this tooth colored posts have gained popularity
      especially in aesthetic areas. Besides aesthetics, the post is also responsible
      for transmitting the occlusal forces to the remaining tooth structure making the
      mechanical properties of the post critical. However, there is no clear consensus
      regarding an ideal system as far as strength of the post is concerned. Hence this
      study aims to analyses and compares the fracture strength of traditional
      prefabricated glass fibre posts with zirconium oxide posts constructed using CAD
      CAM technology.

PMID- 22131667
TI  - A Functional Stress Analysis in the Maxillary Complete Denture Influenced by the
      Position of Artificial Teeth and Load Levels: an In-vitro Study.
AB  - The fracture of complete dentures fabricated using Polymethyl methacrylate resin
      constitutes a challenge to the clinician and remains an unresolved problem. To
      determine whether gradual increase in load or different posterior teeth positions
      in maxillary denture would influence the pattern of stress. Two groups of
      maxillary dentures were fabricated with different posterior teeth positions
      (Group I with teeth on the crest of the ridge; Group II with buccal to the crest
      of the ridge.) using casts prepared from prefabricated edentulous molds, with 5
      dentures in each group. Two strain gauges were cemented on to the midline of each
      denture, one on the anterior palatal area and other on the posterior palatal
      area. The dentures were loaded from 0 to 110 N in steps of 10 N, and the strains
      induced were measured. Differences of the stress magnitudes between the 2 groups
      were statistically analyzed using Mann-Whitney U test. The anterior palatal area
      of the maxillary denture was dominated by a tensile stress, which was greater in
      the group II than in group I. The posterior palatal area was dominated by
      compressive stress but the outer placement of the maxillary teeth caused a
      significant decrease in the compressive stress. The high anterior tensile stress
      with compressive stress in the posterior palatal area during loading may be
      responsible for denture base fractures that initiate from the anterior palatal
      area. The buccal placement of posterior teeth may play a role in the fatigue
      fracture of the maxillary denture.

PMID- 22131668
TI  - An impression technique for preserving interdental papillae.
AB  - An esthetic revolution is occurring in dental profession. The esthetic treatment
      enhances appearance, improve smiles, restore function and raise self esteem. This
      is now well known that both teeth and gums make good smile and good facial
      esthetic. Sometimes while doing treatment in esthetic zone, impression procedure
      can cause strangulation of interdental papilla, causing loss of papillae. This
      article therefore describes a new impression technique that involves the matrix
      impression system and "every other tooth" technique.

PMID- 22131669
TI  - Telescopic overdenture supported by a combination of tooth and an implant: a
      clinical report.
AB  - The conventional modality of treatment of partial edentulousness with reduced
      number of teeth was to render them complete edentulous and provide them complete
      denture or an overdenture with support of few remaining teeth. The goal of
      maintenance of roots are to prevent alveolar bone resorption, provide better load
      transmission, maintain sensory feedback and achieve better stability of denture
      with emphasis on psychological aspect of not being completely edentulous. Over
      the recent past titanium dental implants have been successfully used as tooth
      replacement with predictable results. A combination of tooth and implant support
      is well documented for fixed partial dentures but rarely for overdentures. This
      clinical report aims at evaluation of tooth root and implant supported mandibular
      overdenture treatment with telescopic coping.

PMID- 22131670
TI  - Use of diagnostic and surgical stent: a simplified approach for implant
      placement.
AB  - Dental implantology has emerged as a practical alternative to traditional
      prosthodontics. Since the beginning, placement of implant in the bone to achieve
      a prosthetic solution that fulfils biologic, aesthetic and biomechanical
      requirements has been a challenge. In the past, implant site and inclination were
      dictated by residual bone quality. The desire for predictable prosthesis led to
      the development of prosthetically guided implantology. This concept establishes
      the correct implant position during the diagnostic stage according to planned
      definitive restoration. In prosthetically guided implantology where ideal
      placement of implant is determined by the definitive restoration, use of
      radiographic and surgical stent in conjunction with dental CT scan can play an
      important role. A stent is an appliance used for radiographic evaluation during
      treatment planning for implant placement and during surgical procedures to locate
      optimal implant placement site. The stent with dental CT scan enables the dental
      team to identify specific sites of prospective implant surgery and hence
      determines the optimal position and angulation of implant relative to occlusal
      load. Aided by stent the surgeon can avoid undesirable implant site preparation
      and minimize unnecessary osteotomy, resulting in favorable design of prosthesis,
      reduced surgical trauma, reduced surgical time and increased patient comfort.
      This case report is an insight into the method of fabrication of simple and cost
      effective stent for implant placement and its advantages over the other
      techniques of stent fabrication.

PMID- 22131671
TI  - Oral rehabilitation of a young adult with amelogenesis imperfecta: a clinical
      report.
AB  - This clinical report describes a multidisciplinary approach for the oral
      rehabilitation of a young adult patient diagnosed with hypoplastic amelogenesis
      imperfecta with a skeletal Class III malocclusion. The specific objectives of
      this treatment were to eliminate tooth sensitivity while enhancing esthetics and
      restoring masticatory function. The reverse horizontal overlap of posterior teeth
      was maintained. Treatment included removal of few teeth, lengthening of the
      maxillary and mandibular clinical crowns, and placement of anterior and posterior
      metal-ceramic fixed partial dentures. The third month recall examination revealed
      no pathology associated with the rehabilitation, and the patient's esthetic and
      functional expectations were satisfied.

PMID- 22131672
TI  - Two-piece denture-obturator prosthesis for a patient with severe trismus: a new
      approach.
AB  - Prosthetic intervention with maxillary obturator prosthesis is necessary to
      restore the contours of resected palate and to recreate the functional separation
      of the oral cavity and sinus and nasal cavity. Trismus occurs most frequently in
      maxillectomy patient following surgical procedure. Absence of graft placement and
      healing by secondary intention always results in healing contracture and trismus.
      Trismus could also be a result of post radiation sclerosis and scarring of
      muscles. Two-piece denture-obturator prosthesis is an alternative management to
      conventional acrylic resin obturator prosthesis for the patient with severe
      trismus as patient could not insert a large prosthesis in the mouth. The use of
      flexible or resilient material affords the opportunity to engage in undercut
      areas, needed to help in the retention of the prosthesis, without causing trauma
      to the soft, often sensitive, and easily irritable tissues.

PMID- 22131673
TI  - Prosthodontic Rehabilitation in Sjogren's Syndrome with a Simplified Palatal
      Reservoir: Two Year Follow Up.
AB  - Sjogren's syndrome is a distinct clinical condition which includes xerostomia,
      ocular dryness, rheumatoid arthritis and other connective tissue disorders. Major
      oral problems reported by such patients include high caries rate, burning of oral
      mucosa, early tooth loss, increased tooth wear, poor tolerance for dentures and
      repeated failure of dental restorations. Prosthodontic therapy for this unique
      patient group is challenging and neglected due to the limited number of
      abutments, loss of vertical dimension and poor occlusion. Two year follow up of a
      patient of Sjogren's syndrome, rehabilitated by a combination of fixed and
      removable prostheses with a simplified palatal salivary reservoir is presented.
      Though the patient felt an improvement in quality of life due to the prosthesis,
      slurred speech and frequent reservoir refilling remained problems.

PMID- 22131674
TI  - Hybrid maxillofacial prosthesis: a case report.
AB  - The role of a prosthodontist in the management of cleft lip & palate patients is
      pertinent involving restoration of mastication, facial harmony, dental harmony
      and phonation. This article presents the prosthodontic rehabilitation of a
      congenitally bilateral cleft lip and palate patient with a unique method which
      fulfilled the patient's needs, esthetics and psychological well being.

PMID- 22131675
TI  - Study of Preparation and Standardization of 'Maadhutailika Basti' with special
      reference to Emulsion Stability.
AB  - 'Basti' is compared with conventional enema due to its similarity in procedure of
      administration. But in effect enema is a simple evacuation technique, whereas
      'Basti' is a therapeutic measure considered as 'Ardha Chikitsa' i.e half therapy
      in the disease management. Constitution of 'Basti dravya' formulation
      specifically 'Aasthaapana Basti' has a direct impact on the end result of 'Basti'
      therapy. A systematic stepwise procedure of preparation of 'Aasthaapana Basti' is
      described in Ayurvedic Classics. The present study evaluates the significance of
      this procedure through standardization of 'Maadhutailika Basti', a type and
      standard of 'Aasthaapana Basti'. Four samples of 'Aasthaapana Basti' including
      the classical one were prepared for this study by replacement, exclusion and
      supplementation of honey in the formulation. A comparative study of physico
      chemical characteristics of these samples was carried out. The stability of the
      constitution of 'Maadhutailika Basti' was also studied to assess the role of
      honey as a natural emulsifying agent. The study underlines the significance of
      the procedure described in the classics emphasizing the role of honey as a
      natural emulsifying agent in standardization of 'Maadhutailika Basti'.

PMID- 22131676
TI  - Process standardization of rasamanikya.
AB  - Rasamanikya is a famous drug, frequently used by Ayurvedic physicians for Vata
      Kaphaja diseases like Shwasa, Kasa and Kushtha (Skin disorders). Various methods
      of preparation have been found described in Rasa classics. Generally it is
      prepared by Shuddha Haratala which is kept between two thin transparent Abharaka
      Patra (mica sheets) in small scale and in sharava for large scale, heated up to
      desired level. There are so many methods and different liquid media have been
      found described for Shodhana of Haratala. Therefore the methods of preparation of
      Rasamanikya and Shodhana process of Haratala have been validated through various
      experiments. Tankana-treated Haratala (T. Treated) is found best for Shodhana
      process and final product too i.e. Rasamanikya in terms of pharmaceutical
      standards i.e. Ruby in colour, along with reproducibility of fixed quality.

PMID- 22131677
TI  - Random Estimate the values of seed oil of Cucurbita maxima by refractive index
      method.
AB  - The crude oil having lower iodine and free fatty acids values has Aamdosha
      properties. These properties are present due to toxic and anti-toxic compounds.
      These compounds can be harmful for the special diseases and may be unsaturated,
      saturated, open chain etc. The adulteration can take part as catalytic action for
      the toxic effect for the special diseases. Toxic properties of oils are removed
      by different ingrediants and methods. C. maxima seed tail (mst) is used with food
      and medicine. The present paper deals with the study of oil by refractive index
      and equations.

PMID- 22131678
TI  - Role of different media in Karpanpatru Taila preparation.
AB  - Total six samples of Karpanpatru Taila were prepared with Murchchhita and
      Amurchchhita Sarshapa Taila (mustard oil) by using three different liquid media
      i.e. Gomutra, Takra and Kanji by following classical method and analyzed. The
      pharmaceutical analysis revealed that the Karpanpatru Taila prepared with
      Murchchhita Sarshapa taila by using Kanji, Gomutra, Takra as a liquid media
      showed minimum loss i.e. 4.00%, 8,33% & 8.66 respectively in comparison to
      Amurchchhita Sarshapa Taila by using Kanji, Gomutra, Takra i.e. 5.5%, 10.68%, 12%
      respectively. Pharmaceutical drawbacks like excessive frothing and burning of
      eyes & nose were absent during the preparation of Karpanpatru Taila with Takra
      and Kanji while present in batch of Gomutra. Analytical study reveals that Acid
      value was negligible increased after even 6 month in the samples of Murchchhita
      Karpanpatru Taila while significant increased in the samples of Amurchchhita
      Karpanpatru Taila. Saponification value was decreased in the samples of Murchhita
      Karpanpatru Taila while increased in the samples Amurchchhita Karpanpatru taila.
      Microbial growth was found absent in all the samples of Karpanpatru Taila even
      after 6 months.

PMID- 22131679
TI  - Evaluation of Dhatri Avaleha as adjuvant therapy in Thalassemia (Anukta Vyadhi in
      Ayurveda).
AB  - Thalassemia is the commonest single gene disorder in India. About 10,000 infants
      with Thalassemia major are born every year. The present study was under taken
      with a hope to prevail better quality of life to the Thalassemic patients. Pallor
      being the chief complaint, a randomized controlled trial was undertaken with
      Dhatri Avaleha as it is specially mentioned for Pandu, Kamala & Haleemaka Roga.
      Children between age group of 1 to 15 years were randomly divided in two groups:
      Drug treated group (Group A) and Control group (Group B). Assessment was done on
      subjective and objective parameters after 30 and 60 days of treatment with follow
      up of two month. Statistically significant (P<0.01) result was obtained in Blood
      transfusion interval in group 'A' in comparison to group 'B'. Dhatri Avaleha may
      have a potential to increase blood transfusion interval and decrease secondary
      infection and thus it can be used as supportive therapy with modern medical
      management.

PMID- 22131680
TI  - Clinical efficacy of Ayurveda treatment regimen on Subfertility with Poly Cystic
      Ovarian Syndrome (PCOS).
AB  - Poly Cystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of
      reproductive age, resulting from insulin resistance and the compensatory
      hyperinsulinemia. This results in adverse effect on multiple organ systems and
      may result in alteration in serum lipids, anovulation, abnormal uterine bleeding
      and infertility. According to Ayurvedic view PCOS can be correlated with Aarthava
      Kshaya. It was revealed that most of subfertility patients who were presented
      Osuki Ayurveda Centre suffered from the PCOS. Therefore the present study was
      carried out for the clinical evaluation of the efficacy of Ayurveda treatment
      regimen on subfertility with PCOS. Total 40 patients were selected by using
      purposive sampling method. According to the Ayurveda theories of Shodhana,
      Shamana and Tarpana, the treatment was conducted in 3 stages for the duration of
      6 months. The response to the treatment was recorded and therapeutic effects were
      evaluated by symptomatic relief and through Trans Vaginal Scan and LH, FSH
      hormone levels. The results revealed that, subfertility due to PCOS can be cured
      successfully by using this Ayurveda treatment regimen.

PMID- 22131681
TI  - Clinical Evaluation of Shilajatu Rasayana in patients with HIV Infection.
AB  - AIDS is one of the serious global health concerns caused by Human Immuno
      Deficiency(HIV) virus and is predominantly a sexually transmitted disease.
      Currently there is no vaccine or cure for AIDS still Anti Retroviral Therapy
      (ART) is successful. It reduces both the mortality and the morbidity of HIV
      infection, but is expensive and inaccessible in many countries. However intense
      the therapy may be, HIV virus is rarely eliminated, and drug resistance is a
      major setback during long-term therapy. The development of new drugs and
      strategies and exploring alternative systems of medicine for antiviral herbs or
      drugs is the need of the age to improve treatment outcomes. Ayurveda describes
      many diseases which incorporate HIV like illness e.g. Rajayakshma, Ojo Kshaya,
      Sannipata jwara etc. HIV infection affects multisystems, chiefly the Immune
      System which can be correlated to Ojo Kshaya. Rasayana Chikitsa is the frontline
      therapy employed to treat Ojus disorders. Therefore Shilajatu (Mineral pitch),
      Centella asiatica (Mandukaparni), Tinospora cordifolia (Guduchi) and Emblica
      officinalis (Amalaki), well known for their Immuno-modulator and antioxidant
      properties were selected to evaluate their role on immune system. The study was
      carried on 20 patients from OPD and IPD of Kayachikitsa, S.S.Hospital, IMS, BHU
      and was randomly allocated into Treated group (Shilajatu+ART) and Control group
      (ART). Treated Group responded better to ART both clinically and biochemically.
      The results show that Shilajatu decreases the recurrent resistance of HIV virus
      to ART and improves the outcome of the therapy.

PMID- 22131682
TI  - Role of rasayana in cure and prevention of recurrence of vicharchika (eczema).
AB  - Generally, skin diseases run a chronic course and the recurrence is very common.
      Mandip and Chandola (2009) reported that Shirishadi Decoction administered orally
      and simultaneously Snuhyadi Lepa applied externally to the patients of
      Vicharchika (Eczema) provided complete remission to 18.2% patients, marked
      improvement to 42.4% patients and moderate improvement to 36.4% patients but the
      recurrence rate was very high i.e. 80%. Charaka, in the context of the treatment
      of Apasmara mentions that in all the chronic diseases, Rasayana drugs should be
      prescribed. As eczema is a chronic disease and its recurrences are very common,
      therefore, it was thought desirable to evaluate the role of the Rasayana drugs in
      the cure and prevention of the recurrence of Vicharchika (Eczema). In this study,
      total 38 patients of Vicharchika (Eczema) were registered, among which 31
      patients completed the full course of treatment. These patients were first
      subjected to Koshtha Shuddhi done with Aragvadha (Cassia fistula) Hima
      administered orally at bedtime for initial eight days. Thereafter 30 ml of
      Shirishadi Decoction and 6 gm of Guduchi (Tinospora cardifolia) and Bhringaraja
      (Eclipta alba) powder was given with Ghrita. Both the drugs were given twice
      daily after meals orally. Simultaneously, Snuhyadi Lepa was applied on the
      eczematous lesions. Results of the study showed that addition of Rasayana drugs
      provided complete remission to 22.6% and checked the recurrence of the disease in
      the 89.5% patients of Vicharchika (Eczema).

PMID- 22131683
TI  - Evaluation of Insomrid Tablet and Shirodhara in the management of Anidra
      (Insomnia).
AB  - The study was conducted in 30 clinically diagnosed patients of Anidra (Insomnia)
      with an objective of clinical evaluation of the efficacy of Shirodhara and Tab.
      Insomrid (proposed herbal formulation) in the management of Anidra (Insomnia).
      These patients were randomly divided into three groups of 10 patients each. In
      was observed that the patients of Group III treated with Tab. Insomrid and
      Shirodhara with milk showed highly significant improvements, whereas the Group II
      treated with Shirodhara and Group I treated with Tab. Insomrid also showed
      significant improvements. No adverse effects were noted in any of the patients
      during the trial period.

PMID- 22131684
TI  - Efficacy of Vasadi Syrup and Shwasaghna Dhuma in the patients of COPD (Shwasa
      Roga).
AB  - Chronic Obstructive Pulmonary Disease (COPD) threatens as emerging public health
      crisis. The two major drivers for this are the ageing of the world's population
      and the impressive, if deplorable, success of the multinational tobacco companies
      at forcing open world markets. One of the most striking aspect of COPD is that it
      is heterogenous. There are many different presentations with differing
      intensities of symptoms and even differing responses to the medication. Sorting
      out, what accounts for this phenomenon and how treatments can be best
      individualised, is of concern to both basic and clinical scientists. COPD is a
      leading cause of morbidity and mortality worldwide and results in a substantial
      economic and social burden to society. It is the sixth most common cause of death
      worldwide and expected to rise to third position by 2020. Several national and
      international agencies like WHO, GOLD, ATS, ERS etc. are working in a direction
      of finding some solution of this wicked problem. In Ayurvedic texts Shwasa Roga
      has been described having symptomatology close to COPD. A study was carried out
      in P.G.Deptt. of Kayachikitsa in R.G.G.P.G.Ayu.College Paprola, H. P. where the
      role and efficacy of two Ayurvedic formulations -Vasadi Syrup and Shwasaghna
      Dhuma was evaluated on 30 patients of COPD selected on the basis of fixed
      inclusion and exclusion criteria in two different groups. In both the groups
      drugs provided significant results based on subjective symptomatological criteria
      and objective spirometric criteria.

PMID- 22131685
TI  - Clinical study on Sandhigata Vata w.s.r. to Osteoarthritis and its management by
      Panchatikta Ghrita Guggulu.
AB  - Sandhigata Vata is the commonest form of articular disorder. It is a type of
      Vatavyadhi which mainly occurs in Vriddhavastha due to Dhatukshaya, which limits
      everyday activities such as walking, dressing, bathing etc. thus making patient
      disabled / handicapped. It being a Vatavyadhi, located in Marmasthisandhi and its
      occurrence in old age makes it Kashtasadhya. Vata Dosha plays main role in the
      disease. Shula Pradhana Vedana is the cardinal feature of the disease associated
      with Sandhishotha with Vata Purna Druti Sparsha, lack of movements of the joints
      or painful movement of the joints. In this study total 49 patients having the
      complaints of Osteoarthritis were randomly divided into 2 groups. In Group A,
      patients were treated with Panchatikta Ghrita Guggulu Vati along with Abhyanga
      and Nadi Swedana and in group B patients were treated with only Abhyanga and Nadi
      Swedana. The data shows that Panchatikta Ghrita Guggulu along with local Abhyanga
      and Nadi Swedana i.e. group A has provided better relief in the disease
      Sandhigata Vata.

PMID- 22131686
TI  - Efficacy of Sri Lankan Traditional Decoction of Katuwelbatu Deduru Katukadi in
      treatment of Kaphaja Shira Shula (Chronic Sinusitis).
AB  - Kaphaja Shira Shula is one of the Shiro Roga. Chronic sinusitis is inflammation
      of the sinuses behind the forehead, cheeks, and eyes, which continues for a long
      time or keeps recurring. Kaphaja Shira Shula can be correlated with Chronic
      Sinusitis. The decoction of Katuwelbatu Deduru Katuka is mentioned in Watika
      Prakaranaya, a book on Sri Lankan Traditional Medicine. The ingredients of this
      decoction are Solanum xanthocarpum, Cuminum cyminum, Nigella sativa, Picroihiza
      kurrota and Clerodendrum serratum. But in this study Saussurea lappa is used
      instead of C. serratum with the experience of traditional physician, Weerasinghe.
      Aim of this study was to scientifically evaluate the efficacy of this decoction
      in Kaphaja Shira Shula. Eighty patients suffering from Chronic sinusitis were
      selected from Ayurveda Teaching Hospital, Borella, Sri Lanka and randomly divided
      into two groups. X-ray of Para nasal sinuses and total white cell count before
      treatment and after treatment were recorded. Group one was treated with 120 ml of
      decoction of Katuwelbatu Deduru Katuka and Group two with 120 ml of placebo twice
      a day for twenty one days. Partial and complete symptomatic relief and reduction
      in esinophil count in the blood were observed in the treated group. It is
      observed that decoction of Katuwelbatu Deduru Katukadiya can be used in treatment
      of Kaphaja Shira Shula (Chronic sinusitis) effectively.

PMID- 22131687
TI  - A clinical study on Adhimantha and it's management with Nayanamrita Lauha and
      Triphaladi Varti.
AB  - Adhimantha is a disease which has been mentioned by Sushruta as an intense
      feeling of the eye, wherein eye seems to be being extracted out and churned up
      alongwith the involvement of the half of the head in association with specific
      features of the particular Dosha involved. Glaucoma is a disease which is
      characterized by raised intra-ocular pressure, optic disc cupping and visual
      field defect. The clinical study was done on 79 patients of Kaphaja Adhimantha in
      4 different groups. Group A was treated with Triphaladi Varti. Group B was
      treated with Nayanamrita Lauha. Group C was combined group wherein both
      Nayanamrita Lauha and Triphaladi Varti were given. Group D was treated with
      placebo eye drop (Saurastra Netra Bindu). After the enrolment of the patients for
      this study, signs and symptoms such as dimness of vision, heaviness in head,
      coloured haloes, optic disc changes, IOP and visual field changes were studied
      before, during and after the treatment. The study indicates that combined group
      showed better results as compared to other groups.

PMID- 22131688
TI  - Clinical Study of An Ayurvedic Compound (Divyadi Yoga) in the Management of
      Shayyamutrata (enuresis).
AB  - Child health has assumed great significance in all over world. Its importance is
      being realized more and more by pediatricians and general public in developing as
      well as developed countries. Enuresis is defined as the voluntary or involuntary
      repeated discharge of urine into clothes or bed after a developmental age when
      bladder control should be established. The present clinical study was planned to
      evaluate the effect of Divyadi Yoga along with counseling in the management of
      Shayyamutra. Total 40 selected cases were divided into two groups, i.e. 20 in
      each group. One group of children were given the trial drug Divyadi Yoga (D(1))
      with counseling and other group of children were given placebo Divyadi Yoga
      (D(2)) with counseling. Divyadi Yoga was given in the dose of 3-6 gms. twice a
      day with luke warm water. The result of the study showed that groups provided a
      highly significant.

PMID- 22131689
TI  - Role of 'krishna tila' and 'arkapushpa taila' uttarbasti in the management of
      artavakshaya.
AB  - Ayurvedic classics give importance to Shuddha Artava and mention that
      Artavadushti is one of the causative factors for infertility. Artavakshaya is not
      separately described as disease any where in Ayurvedic classics, of course, this
      doesn't desecrate Artavakshaya. Because, Acharya Charaka has quoted in Charaka
      Nidana Sthana, first chapter, that symptoms of a disease themselves also
      constitute as a disease. But sometime, because of their subordinate nature they
      are only symptoms and not disease. This quotation substantiates the stand of
      taking 'Artavakshaya' as disease in the present studies. There are many processes
      and methods available in Ayurvedic classics to alleviate Artavakshya. But it is
      yet, the on going research to find out a method of treatment, which is nearer to
      procurance of permanent cure without side effects. It is well known that
      Ayurvedic classics emphasize on both Shodhana and Shamana therapy. Since Vata
      plays key role in Yoniroga, Uttarbasti, being Vata shamana, is a specific
      treatment in diseased condition of Yoni. As Shamana therapy Kwatha preparation
      choose to evaluate its efficacy. In the present study total 37 patients were
      registered, out of them 6 patients were discontinued. One group of patients was
      administered Arkapushpa Taila Uttarbasti and Krishna Tila Kwatha simultaneously.
      It gave more significant result. Krishna Tila Kwatha was administered orally in
      other group. Placebo wheat powder was administered orally in third group.
      Uttarbasti and Kwatha were found highly effective when administered
      simultaneously.

PMID- 22131690
TI  - Clinical study on Laksha Guggulu, Snehana, Swedana & Traction in Osteoarthritis
      (Knee joint).
AB  - The objective of the present research was to study the efficacy of Laksha
      Guggulu, Snehana, Swedana & Traction in the management of Osteoarthritis (Knee
      joint). For the present work, 30 clinically diagnosed patients were selected and
      randomly divided into three groups. Group A treated with Laksha Guggulu orally,
      Group B treated with snehana & swedana traction, Group C treated with Laksha
      Guggulu, Snehana, Swedana & Knee Joint Traction. The various criteria worked upon
      were joint pain, oedema, tenderness, restriction of joint movement, stiffness,
      local crepitation, walking distance. Significant results were obtained on pain in
      joint movement, restriction in joint movement, joint stiffness , local
      crepitation nearly in all the groups with best result in combined group or group
      C.

PMID- 22131691
TI  - Evaluation of adaptogenic and anti-stress effects of Ranahamsa Rasayanaya-A Sri
      Lankan classical Rasayana drug on experimental animals.
AB  - Various types of stress not only harm the mental function, but also cause
      diseases by weakening body defenses. Rasayana therapy has an advantage over the
      conventional Kayachikitsa treatment in such conditions, as it is capable of
      counteracting the stress, promote the adaptogenic abilities of the body, enhance
      mental endurance, etc. These are the some of parameters for evaluation the
      rasayana effect of a drug, therefore the same have been studied to assess the
      rasayana effect of Ranahamsa Rasayanaya (RR). Experimental models such as forced
      swimming induced hypothermia and stress induced gastric ulcer formation have been
      carried out befitting on Charles Foster strain albino rats to determine the
      rasayana effect of RR. Statistically highly significant decrease in forced
      swimming induced hypothermia and non-significant decrease in gastric ulcer
      formation were observed in the treatment groups, when compared to the stress
      control group. These results show the probable adaptogenic and anti-stress
      activities of the test drug. The study results support the claims made by the Sri
      Lankan traditional practitioners that, the test drug is a potent rasayana
      formulation.

PMID- 22131692
TI  - A comprehensive review of Cataract (Kaphaja Linganasha) and its Surgical
      Treatment in Ayurvedic Literature.
AB  - Ayurveda the science of life, since its origin is serving the mankind throughout
      in health & disease state of life. Shalakyatantra, one of its specialized branch
      deals with the science of Ophthalmology, Otorhinolaryngology, Orodental surgery &
      Head; was contributed and developed by Rajrishi Nimi, the King of Videha, who was
      a colleague of Atreya, Punarvasu, Dhanwantri, Bharadwaja, Kashyapa etc. The
      available literature related to this speciality is reproduced from original text
      of Nimitantra in Uttartantra of Sushruta samhita. So Rajrishi Nimi deserves all
      the credit and regards for Shalakyatantra and for being the first eye surgeon on
      this earth. The fact regarding the technique of cataract surgery adopted by
      ancient surgeons is still a matter of debate. Most of the medical fraternity
      accepts cataract surgery of ancient surgeons as couching procedure but after
      going through forth coming pages, the prevailing concept will prove to be a myth.
      It started with extra capsular extraction through small incision during the
      period of Sushruta Samhita but later shifted to couching like technique by
      Acharya Vagbhatta. Secondly, the objective of this literary research paper is to
      find proper co-relation of the disease cataract to those mentioned in Ancient
      Ayurvedic classic. Linganasha has been inadvertently taken as cataract but this
      is neither logical nor in accordance with classics. We find detailed description
      of cataract's differential diagnosis, indications, contra- indications,
      pre/intra/post operative procedures and complication in ancient texts of
      Ayurveda. Not only this, vivid description of treatment of various complications
      of cataract surgery are also given. Needless to say, no other surgically
      treatable diseases & its complications except Kaphaja Linganasha are given this
      much attention.

PMID- 22131693
TI  - Concept of Ahara in relation to Matra, Desha, Kala and their effect on Health.
AB  - For evaluation of the effect of Ahara on Health in relation to Matra, Desha and
      Kala, an interview based survey study was carried out by simple randomized
      selection of healthy and unhealthy individuals. It was found that consideraton of
      Matra, Desha and Kala in aspect of Ahara taking were found beneficial for health.

PMID- 22131694
TI  - Therapeutic uses of Swarnamakshika Bhasma (A Critical Review).
AB  - Mineral drugs play an important role in Ayurvedic therapeutics. Looking to the
      superiority of the metals and minerals to that of herbal and animal drugs, the
      Rasavaidyas went on experimenting clinical trials over lot of metals and minerals
      and systematically separated some of them which were exclusively active
      therapeutically. Swarnamakshika is one such mineral which after proper
      purification and incineration become highly potent and utilised for diseases like
      Jwara, Pandu, Prameha, Shwasa, Kasa, Kushtha, Anidra, Apasmar etc.

PMID- 22131695
TI  - Prevalence of touch sensation (sparshanendriya-vyapaktva).
AB  - There are much more topics in our Ayurvedic classics about which we have limited
      knowledge. Like this an another topic is Indriya. We don't know what is indriya
      or what are their sites. Are the organs by which we perceive sensation called
      Indriya or different from them? Acharya Charaka has told five types of Indriyas,
      Sparshanendriya, Chakshurendriya, Ghranendriya, Rasanendriya & Shravanendriya. He
      also described their sites, functions, composition, and their properties. But he
      also told that Sparshanendriya is the main Indriya and it is present in all
      Indriyas. Why Charaka told that Sparshanendriya is Vyapak in all Indriyas. Is
      this concept wrong or right? The answer is right & this concept can be proved by
      following means as described in this paper.

PMID- 22131696
TI  - Micro-organisms in Vedas.
AB  - The word krimi is used in Veda for different macroscopic & microscopic creatures.
      Right from bacteria, various insects like kita, patanga were nominated as krimi.
      Two types of krimi viz. Drishta (Visible/Macroscopic) & Adrishta (Invisible /
      Microscopic) were described in veda. These two categories encompases nearly all
      krimi (Microbes / pathogens). According to their origin & Habitat they were
      categorized as pranyashrayee & Anyasthanashrayee. Different sharirika, manasika &
      adhyatmic vyadhis were thought to be originated from these Krimis. These harmful
      & debilitates (Pushtinashaka) organisms were recognized by various names based on
      troubles/sufferings they produce. Sun & Agni (fire) were described as internal
      source of krimichikitsa. Today science also confirms this fact. That early
      morning ultraviolet light rays emanating from sun can be used for various
      krimijanya-vyadhis. Apart from this various treatment modalities by using various
      natural resources, vegetable drugs. mineral drugs, fumigation, cleansing (Marjan
      prokshana) & hymns were described for krimi & diseases caused by them.

PMID- 22131697
TI  - Prajwalito dnyanamayah pradeepah....

PMID- 22131698
TI  - From the desk of the Editor.

PMID- 22131699
TI  - Editorial.

PMID- 22131700
TI  - The effect of ghee (clarified butter) on serum lipid levels and microsomal lipid
      peroxidation.
AB  - Ghee, also known as clarified butter, has been utilized for thousands of years in
      Ayurveda as a therapeutic agent. In ancient India, ghee was the preferred cooking
      oil. In the last several decades, ghee has been implicated in the increased
      prevalence of coronary artery disease (CAD) in Asian Indians due to its content
      of saturated fatty acids and cholesterol and, in heated ghee, cholesterol
      oxidation products. Our previous research on Sprague-Dawley outbred rats, which
      serve as a model for the general population, showed no effect of 5 and 10% ghee
      supplemented diets on serum cholesterol and triglycerides. However, in Fischer
      inbred rats, which serve as a model for genetic predisposition to diseases,
      results of our previous research showed an increase in serum total cholesterol
      and triglyceride levels when fed a 10% ghee-supplemented diet. In the present
      study, we investigated the effect of 10% dietary ghee on microsomal lipid
      peroxidation, as well as serum lipid levels in Fischer inbred rats to assess the
      effect of ghee on free radical mediated processes that are implicated in many
      chronic diseases including cardiovascular disease. Results showed that 10%
      dietary ghee fed for 4 weeks did not have any significant effect on levels of
      serum total cholesterol, but did increase triglyceride levels in Fischer inbred
      rats. Ghee at a level of 10% in the diet did not increase liver microsomal lipid
      peroxidation or liver microsomal lipid peroxide levels. Animal studies have
      demonstrated many beneficial effects of ghee, including dose-dependent decreases
      in serum total cholesterol, low density lipoprotein (LDL), very low density
      lipoprotein (VLDL), and triglycerides; decreased liver total cholesterol,
      triglycerides, and cholesterol esters; and a lower level of nonenzymatic-induced
      lipid peroxidation in liver homogenate. Similar results were seen with heated
      (oxidized) ghee which contains cholesterol oxidation products. A preliminary
      clinical study showed that high doses of medicated ghee decreased serum
      cholesterol, triglycerides, phospholipids, and cholesterol esters in psoriasis
      patients. A study on a rural population in India revealed a significantly lower
      prevalence of coronary heart disease in men who consumed higher amounts of ghee.
      Research on Maharishi Amrit Kalash-4 (MAK-4), an Ayurvedic herbal mixture
      containing ghee, showed no effect on levels of serum cholesterol, high density
      lipoprotein (HDL), LDL, or triglycerides in hyperlipidemic patients who ingested
      MAK-4 for 18 weeks. MAK-4 inhibited the oxidation of LDL in these patients. The
      data available in the literature do not support a conclusion of harmful effects
      of the moderate consumption of ghee in the general population. Factors that may
      be involved in the rise of CAD in Asian Indians include the increased use of
      vanaspati (vegetable ghee) which contains 40% trans fatty acids, psychosocial
      stress, insulin resistance, and altered dietary patterns. Research findings in
      the literature support the beneficial effects of ghee outlined in the ancient
      Ayurvedic texts and the therapeutic use of ghee for thousands of years in the
      Ayurvedic system of medicine.

PMID- 22131701
TI  - Studies on the physicochemical characteristics of heated honey, honey mixed with
      ghee and their food consumption pattern by rats.
AB  - Honey and ghee are the two food substances used widely in our diet. In Ayurveda,
      it is quoted that heated honey and honey mixed with equal amount of ghee produce
      deleterious effects. Hence, it was of our interest to study the physicochemical
      characteristics and chemical constituents of heated honey and honey mixed with
      ghee, and their effect on daily food intake and organ weights of rats. The
      specific gravity of samples showed a significant decrease in honey and ghee
      samples heated to 140 degrees C. The pH of honey heated to 140 degrees C was
      elevated with a reduction in the specific gravity. There was a significant rise
      in hydroxymethyl furfuraldehyde (HMF) in 60o and 140 degrees C heated honey
      samples. The browning and total antioxidant of honey mixed ghee samples was
      significantly higher when compared to ghee samples. Further, the authors have
      also evaluated the effects of consumption of heated honey, ghee, honey mixed with
      equal amount of ghee and heated honey mixed with heated ghee in rats. The feeding
      of heated honey and honey mixed with ghee for 6 weeks showed no significant
      change in the food intake, weight gain and relative organ weights. The study
      revealed that the heated honey mixed with ghee produces HMF which may cause
      deleterious effects.

PMID- 22131702
TI  - Evaluation of some objective parameters for Ushna and Sheeta Gunas based on
      pharmacological study.
AB  - In the formation of a principle, the experimental study plays a pivotal role.
      After repeated experiments under the same conditions, if one finds the same
      results, then a principle is formed. Ayurvedic principles which were formulated
      on the basis of keen observations and through special senses need to be
      reassessed through contemporary scientific tools. The principles of Ushna (hot)
      and Sheeta (cold) Gunas (properties) need to be assessed and evaluated through
      various animal experiments so as to suggest parameters which can be suitable for
      the evolution of these Gunas. The present study is an attempt to find out the
      possibility of employing simple experimental parameters to assess these Gunas in
      selected drug substances and the data generated through this study were analyzed.
      The obtained results are encouraging to develop the same. All details are
      presented in this paper.

PMID- 22131703
TI  - Experimental evaluation of antidepressant effect of Vacha (Acorus calamus) in
      animal models of depression.
AB  - Depression is a common diagnosis throughout India. It is one of the major
      sequelae of modern lifestyle which is full of stress. Several drugs and therapies
      have been tried but a safe and effective treatment of depressive illness is yet
      not fully established. The main objective of this experimental study on animal
      models is to evaluate the antidepressant action of plant drug Vacha (Acorus
      calamus). The behavioral study was conducted and at the same time 5-HT receptor
      involvement was evaluated. The experimental study was done in rats to evaluate
      their Open Field Behavior (OFB), High Plus Maze (HPM) activity and 5
      hydroxytryptamine (5-HT) receptor syndrome, before and after feeding Vacha.
      Concurrent Vacha administration in the depression model prevented the development
      of behavioral deficit in ambulation and rearing due to stress. Similarly, in High
      Plus Maze Test (HPMT), exploratory activity of rat was restored with Vacha
      administration. In adopted model of depression, when the animal was subjected to
      Vacha administration, the behavioural deficit was prevented very well as compared
      to stressed group. While eliciting the 5-HT syndrome, only two components out of
      five were influenced by Vacha, indicating that Vacha does not sensitize
      postsynaptic 5-HT1A receptors, which explains the behavioral deficit prevention
      in stressed rat group. Vacha definitely has antidepressant effects in animal
      model of depression.

PMID- 22131704
TI  - Infertility caused by tubal blockage: An ayurvedic appraisal.
AB  - Tubal blockage is one of the most important factors for female infertility. This
      condition is not described in Ayurvedic classics, as the fallopian tube itself is
      not mentioned directly there. The present study is an effort to understand the
      disease according to Ayurvedic principles. Correlating fallopian tubes with the
      Artavavaha (Artava-bija-vaha) Srotas, its block is compared with the Sanga
      Srotodushti of this Srotas. Charak's opinion that the diseases are innumerable
      and newly discovered ones should be understood in terms of Prakriti, Adhishthana,
      Linga, and Aayatana, is followed, to describe this disease. An effort has been
      made to evaluate the role of all the three Doshas in producing blockage, with
      classification of the disease done as per the Dasha Roganika.

PMID- 22131705
TI  - Critical analysis of herbs acting on Mutravaha srotas.
AB  - Ayurveda has given prime importance to Mutravaha srotas (urinary system) and
      Srotogata Vikaras (urinary disorders). Being a system responsible for homeostasis
      of fluids in the body it also detoxifies the body by eliminating certain waste
      products through urine. When diseased, people produce symptoms such as, increased
      or decreased urine production, painful maturition, formation of stones, and
      thereby obstructed micturition, increased frequency of micturition, and so on.
      There are many herbs with varied actions specifically aimed at mitigating urinary
      system disorders. Drugs such as Jambu, Amrasthi, and the like, reduce the
      increased flow of urine, and hence, are considered as Mutrasangrahaneeya,
      whereas, drugs like Ikshu, Kustha, and so on, increase the flow of urine, and
      hence, are considered as Mutravirechaneeya. There are drugs like Padma, Utpala,
      and so on, which impart normal color to the urine and are known as
      Mutravirajaneeya dravyas. Asmarighna dravyas break down the calculi and remove
      them through the urine. These dravyas, when used under proper direction, help in
      relieving the pain and apathy caused by the disease.

PMID- 22131706
TI  - 'Swapna' in the Indian classics: Mythology or science?
AB  - There are many concepts in Ayurveda as well as the ancient sciences that are
      untouched or unexplored. One such concept is that of the Swapna (dreams). Being
      an abstract phenomenon it makes it difficult to be explained and understood;
      probably because of this the descriptions related to Swapna in the Indian
      classics are supported by mythology, to make them acceptable. Variations in these
      explanations are seen according to the objective of the school of thought; that
      is, in the ancient texts where dreams are used to delve into the knowledge of the
      Atman and are related to spirituality, its description in the Ayurvedic texts
      evolves around the Sharira and Manas. Although all these explanations seem to be
      shrouded in uncertainty and mythology; there definitely seems to be a logical and
      rational science behind these quotations. They only need research, investigation,
      and explanation on the basis of logic, and a laboratory.

PMID- 22131707
TI  - Shad Garbhakara Bhavas vis-a-vis congenital and genetic disorders.
AB  - Despite the advancements in diagnostic techniques and therapeutic interventions,
      medical science has failed to keep the incidence of congenital malformations
      under control. Ayurveda, the ancient Indian medical system has given due emphasis
      on this and postulated various measures to minimize the risks. These measures
      start well before conception. According to Ayurvedic principles, proper
      preparation of the parents is an essential prerequisite for a healthy progeny.
      Pre-conception care is a set of interventions that identifies biomedical
      behavioral and social risks to the health of the mother and the baby. It includes
      both-prevention and management, emphasizing health issues that require action
      before conception, very early in pregnancy, for maximal impact. For meeting the
      objective of healthy progeny, Ayurveda scholars felt the importance of six
      procreative factors (Shadgarbhkarabhavas) such as Matrija, Pitrija, Aatmaja,
      Rasaja, Satmyaja, and Sattvaja. The conglomeration of these procreative factors
      is must for healthy progeny. The physical, mental, social, and spiritual well
      being of the person, proper nutrition of the mother during pregnancy, and
      practice of a wholesome regimen, play a prime role in achieving a healthy
      offspring, thus structuring a healthy family, society, and nation. Negligence
      toward any of these factors becomes a cause for unhealthy and defective child
      birth. The present literary / conceptual study, thus focuses mainly on
      interpreting these observations, on the basis of modern scientific knowledge.

PMID- 22131708
TI  - A clinical comparative study of the management of chronic renal failure with
      Punarnavadi compound.
AB  - India like any other country is facing a silent epidemic of chronic renal failure
      (CRF)- a facet of the health transition associated with industrialization partly
      fuelled by increase in sedentary lifestyle, low birth weight and malnutrition.
      Increasing figures by many folds seen is posing a difficult situation to overcome
      with respect to economy and health of the working and earning population of the
      nation. There is an urgent need to explore, highlight new interventions and
      modify modifiable risk factors as a basis for treatment strategies to prevent the
      development and progression of CRF. The present study was taken up to evaluate
      the role of trial formulation tab. Punarnavadi compound in the management of
      chronic renal failure. This was an open clinical comparative study in controlled
      circumstances wherein 67 patients were studied for two months in three groups-
      Group A (allopathic control), Group B (ayurvedic control) and Group C (ayurvedic
      test). It was a multi-centric study; patients were registered from Anandababa
      charitable dialysis centre, Jamnagar, Kayachikitsa O.P.D. of I.P.G.T. and R.A.
      Jamnagar and P. D. Patel Ayurveda hospital, Nadiad. Results were assessed on 15
      parameters using Students (paired) 't' test. Group A patients showed
      comparatively better results in eight parameters- weight, platelet count, serum
      urea, serum uric acid, serum sodium, potassium, chloride and total proteins.
      Parameter Hemoglobin% showed better results in Group B patients and in Group C
      patients comparatively better results in six parameters viz.- quality of life
      (breathlessness, weakness, general functional capacity), total count, serum
      creatinine and serum calcium - were observed. Throughout the study, trial drug
      tab. Punarnavadi compound did not show any adverse drug reaction. The results of
      this study will help in developing a cheap and safe treatment for the management
      of CRF.

PMID- 22131709
TI  - A clinical trial of Sri Lankan traditional decoction of Pitawakka Navaya in
      treatment of Kaphaja Shirsha Shoola (chronic sinusitis).
AB  - Authentic Ayurvedic texts mention eleven types of Shiro Roga (diseases in head).
      Kaphaja Shirsha Shoola, which occurs due to vitiation of Kapha and Vata Dosha, is
      one of them. Chronic sinusitis is a chronic inflammation of sinuses. It can be
      correlated with Kaphaja Shirsha Shoola. Decoction of Pitawakka Navaya consists of
      nine ingredients. They are Bhoomyamalaka, Haritaki, Bharangi, Chavya, Pippali,
      Salarka, Guduchi, Shunti and Maricha. These herbs, which pacify vitiated Vata
      Dosha and Kapha Dosha, are used by traditional physicians in Sri Lanka to treat
      Kaphaja Shirsha Shoola (chronic sinusitis). However, no scientific studies have
      been conducted to evaluate the efficacy of Pitawakka Navaya in treatment of
      Kaphaja Shirsha Shoola. Hence, this clinical study has been conducted to evaluate
      its efficacy.. Sixty patients suffering from Kaphaja Shirsha Shoola were selected
      and examined. These patients were randomly divided into two groups of thirty
      patients each. First group was treated with 120 ml of decoction of Pitawakka
      Navaya twice a day for fourteen days. The second group was treated with 120 ml of
      placebo twice a day for fourteen days. After treatment, most of the patients'
      symptoms were completely or partially relieved. In less than 10% of patients,
      some symptoms were unchanged or aggravated. It is observed that traditional
      decoction Pitawakka Navaya is beneficial for Kaphaja Shirsha Shoola (chronic
      sinusitis).

PMID- 22131710
TI  - A short-term intervention trial on HIV positive patients using a Sri Lankan
      classical rasayana drug - Ranahamsa Rasayanaya.
AB  - Rational use of Rasayana therapy, in the management of HIV infected individuals,
      could potentially stabilize the destructive control mechanisms, by modulating the
      psycho-neuro-endocrine-immune axis. The objective of the present study has been
      to determine the short-term effects of Ranahamsa Rasayanaya (RR) in HIV infected
      patients. A total of 27 patients with documented HIV infection were randomly
      assigned to two groups, Group A - 5 g of RR twice daily with cow's milk and
      sugar. Group B - Only routine modern therapy was continued, if any they were
      taking, including highly active anti-retroviral therapy (HAART). Absolute CD4(+)
      T-cell and total lymphocyte counts were measured in these patients, registered
      under Group A. Only 21 participants completed the study protocol (In Group A, 15
      patients and in Group B, 6 patients). Initial mean CD4(+) T-cell count was 304.50
      +/- 43.36 cells/microliter, which increased to 430.44 +/- 66.01 cells/microliter
      by 41.36% (P<0.05), measured among 9 patients out of 15, who received RR in Group
      A. The RR seemed to be a safer adjuvant in people with HIV infection with respect
      to absolute CD4(+) T-cell count over a 90 days treatment.

PMID- 22131711
TI  - A Comparative clinical trial on the role of Panchakarma therapy and Unmada
      Gajankusha Rasa in the cases of major depressive disorder vis-a-vis kaphaja
      Unmada.
AB  - Depression is a common but serious mood disorder which exerts wide range of
      physical, physiological and psychological impact. On the basis of the severity of
      disease, depression is classified under various categories. Of all the types of
      depression, major depressive disorder resembles the features of kaphaja Unmada.
      The patients of Kaphaja Unmada are dirty in appearance, their speech and
      activities are retarded and they prefer to remain in solitude and lonely places.
      The presentstudy has been conducted in eighty patients of major depressive
      disorder dividing them into four groups, A, B, C and D using Vamana therapy and
      Unmada Gajankusha Rasa in the dose of 250 mg twice daily with water. The results
      were assessed on scoring of clinical symptoms and signs and by using Hamilton
      depression rating scale (HDRS).The results reveal the mild to moderate degree of
      response over various parameters which has been presented in detail in the
      article.

PMID- 22131712
TI  - A Clinical study of Matra Vasti and an ayurvedic indigenous compound drug in the
      management of Sandhigatavata (Osteoarthritis).
AB  - Sandhigatavata is described under vatavyadhi in all ayurvedic classical texts.
      Osteoarthritis is the most common articular disorder which begins
      asymptomatically in the second and third decades and is extremely common by age
      70. Here Matra Vasti (therapeutic enema) was given with Bala taila as Vasti is
      the best treatment for vatavyadhies. It has vatashamaka and rasayana properties.
      Indigenous compound drug containing Guggulu, Shallaki, Yastimadhu, Pippali,
      Guduchi, Nirgundi, Kupilu and Godanti was given in one group along with Matra
      Vasti. In this study, 33 patients of Sandhigatavata completed the treatment.
      Patients were randomly divided into two groups. Sixteen patients in Group-A
      (sarvanga Abhyanga-swedana + matravasti) and 17 patients in Group-B (sarvanga
      Abhyanga-swedana+ matravasti + indigenous compound drug). The results of the
      study indicate that the patients of both the groups obtained highly significant
      relief in almost all the signs and symptoms of Sandhigatavata.

PMID- 22131713
TI  - Clinical observation on Greeva Stambha (cervical spondylosis) Chikitsa.
AB  - Greeva Stambha (A Vataja Disorder) simulates cervical spondylosis, which is a
      chronic degenerative condition of the cervical spine. Keeping in view the
      increasing incidence of this problem in modern society with more of desk-
      workers; an observational study was conducted on 22 patients of Greeva stambha
      vis-a-vis cervical spondylosis selected from OPD/IPD of CRIA, Punjabi-Bagh, New
      Delhi, satisfying the inclusion criteria. The Vatahara treatment viz. Maha
      Yogaraj Guggulu 500 mg BD, Panchguna tail for local use and Nadi sweda (Local
      steam with Dashmoola Kwatha) were given for seven days. The results were assessed
      on the basis of symptomatic improvement using visual analog scale.

PMID- 22131714
TI  - A clinical study on Krimidanta with reference to dental caries and its management
      with Jatipatradi Gutika and Yavanadi Churna.
AB  - Dental caries is progressive destruction of enamel, dentine and cementum,
      initiated by microbial activity at the tooth surface. It is one of the major
      problems in dentistry. On the basis of clinical features, it can be compared with
      Krimidanta which is one among the eight diseases of tooth. In the management of
      Krimidanta, Krimighna, Vataghna and Ushna Veerya dravyas are to be used which can
      relieve the toothache and discoloration. In this study, the trial drugs used were
      Jatipatradi Gutika for Pratisarana and Yavanadi Churna for oral administration.
      In this study, the patients of Krimidanta (dental caries) were selected from OPD
      of Shalakya Department and allotted randomly in different groups. In Group A, the
      patients were treated with Jatipatradi Gutika for Pratisarana for 30 days. In
      Group B, the patients were treated with Yavanadi Churna orally and Group C
      patients were treated with combined therapy for 30 days. The clinical study has
      shown that combined therapy gives better results than individual therapies.

PMID- 22131715
TI  - Role of Uttara Vasti with Trivrit and Lasuna oil in the management of primary
      dysmenorrhea.
AB  - Dysmenorrhea is one of the most common clinical entities encountered in regular
      practice by the gynecologists. Dysmenorrhea means painful menstruation. Fifty
      percent of the women suffer from dysmenorrhea. Primary dysmenorrhea is correlated
      with Udavartini yonivyapad in Ayurveda. No successful advances have been made in
      the line of management till today by western medicine. Therefore, a complete,
      comprehensive and holistic approach toward its understanding and treatment is the
      need of the age. In this series, Uttar Vasti, a unique panchakarma procedure, is
      studied for its role in yonivyapads. A research study was conductedto evaluate
      the efficacy of Uttar Vasti with Trivrit and Lasuna oil in Primary dysmenorrhea.
      Thirty-six diagnosed cases of Udavartini Yonivyapad, viz., primary (spasmodic)
      dysmenorrhea, were selected and randomly allocated into two groups. The effect of
      Uttar Vasti was compared with the commonly used non steroidal anti inflammatory
      drug (control group). Uttar Vasti with Operculina turpethum (Trivrit) and Allium
      sativum (Lasuna) oil has shown encouraging results in Udavartini yonivyapad.
      Statistically significant relief was seen in the intensity of pain and the
      successive cycles were less painful in the treated group as compared to control
      group. The mode of action can be attributed to anti-inflammatory (vatahara),
      vasodilatory (ushna virya) antispasmodic and laxative (anulomana) properties of
      the trial drugs. The present study shows Uttar Vasti as a safe and easy technique
      to treat dysmenorrhea like conditions without any side effects.

PMID- 22131716
TI  - The role of Apamarga Kshara in the treatment of Arsha.
AB  - As per the available treatment modalities of Arsha, the Kshara karma modality is
      the best one, taking into the consideration its convenience, easy adoptability,
      cost-effectiveness and curative results. Under this parasurgical procedure,
      various forms of external kshara application are used in treating the Arsha.
      These are Ksharasutra Ligation (KSL), ksharpatan, etc. KSL is a surgical
      procedure, while ksharapatan vidhi is local application and seems to be effective
      with an easy procedure. Several studies of ksharapatan had been conducted; so the
      time has come to specify the study of ksharapatan, e.g., according to degree of
      pile mass and different symptoms and signs. In this present study, apamarga
      (Achyranthus aspera Linn.) kshara, one among the best qualitative ksharas, was
      locally applied directly on the different sizes, shapes and degrees of Arsha, to
      find out its effectiveness with or without any untoward effect. A total of 30
      patients were treated by local application of Apamarga kshara. The ksharapatan
      was done every day, for 7 days in 3 g dose, and the result was assessed
      thoroughly on the basis of observation according to the specially designed
      proforma. Apamarga kshara was prepared as per the standard method described in
      Ayurvedic texts. Patients suffering from Arsha were selected by simple random
      sampling method, with the complaints of bleeding per rectum, Vedana, Srava, kandu
      and prolapse. Lastly, it was concluded that ksharapatan had shown significant
      improvement in 1st and 2nd degree of pile masses without any side effect.

PMID- 22131717
TI  - A clinical study on "Computer vision syndrome" and its management with Triphala
      eye drops and Saptamrita Lauha.
AB  - American Optometric Association (AOA) defines computer vision syndrome (CVS) as
      "Complex of eye and vision problems related to near work, which are experienced
      during or related to computer use". Most studies indicate that Video Display
      Terminal (VDT) operators report more eye related problems than non-VDT office
      workers. The causes for the inefficiencies and the visual symptoms are a
      combination of individual visual problems and poor office ergonomics. In this
      clinical study on "CVS", 151 patients were registered, out of whom 141 completed
      the treatment. In Group A, 45 patients had been prescribed Triphala eye drops; in
      Group B, 53 patients had been prescribed the Triphala eye drops and
      SaptamritaLauha tablets internally, and in Group C, 43 patients had been
      prescribed the placebo eye drops and placebo tablets. In total, marked
      improvement was observed in 48.89, 54.71 and 06.98% patients in groups A, B and
      C, respectively.

PMID- 22131718
TI  - A comparative study of Agni karma with Lauha, Tamra and PanchadhatuShalakas in
      Gridhrasi (Sciatica).
AB  - Sushruta has mentioned different methods of management of diseases, such as
      Bheshaja karma, Kshara Karma, Agni karma, Shastrakarma and Raktamokshana. The
      approach of Agni karma has been mentioned in the context of diseases like Arsha,
      Arbuda, Bhagandar, Sira, Snayu, Asthi, Sandhigata Vata Vikaras and Gridhrasi.
      Gridhrasi is seen as a panic condition in the society as it is one of the burning
      problems, especially in the life of daily laborers. It is characterized by
      distinct pain starting from Sphik Pradesha (gluteal region) and goes down toward
      the Parshni Pratyanguli (foot region) of the affected side of leg. On the basis
      of symptomatology, Gridhrasi may be simulated with the disease sciatica in modern
      parlance. In modern medicine, the disease sciatica is managed only with potent
      analgesics or some sort of surgical interventions which have their own
      limitations and adverse effects, whereas in Ayurveda, various treatment
      modalities like Siravedha, Agni karma, Basti Chikitsa and palliative medicines
      are used successfully. Among these, Agni karma procedure seems to be more
      effective by providing timely relief. Shalakas for Agni karma, made up of
      different Dhatus like gold, silver, copper, iron, etc. for different stages of
      the disease conditions, have been proposed. In the present work, a comparative
      study of Agni karma by using iron, copper and previously studied Panchadhatu
      Shalaka in Gridhrashi has been conducted. A total of 22 patients were treated in
      three groups. Result of the entire study showed that Agni karma by Panchadhatu
      Shalaka provided better result in combating the symptoms, especially Ruka and
      Tandra, while Lauhadhatu Shalaka gave better results in combating symptoms of
      Spanadana and Gaurava. In the meantime, Tamradhatu Shalaka provided better effect
      in controlling symptoms like Toda, Stambha and Aruchi. Fifty percent patients in
      Panchadhatu Shalaka (Group A) were completely relieved. In Lauhadhatu Shalaka
      (Group B), the success rate was 00.00%, and in Tamradhatu Shalaka (Group C), the
      percentage of success rate was 14.28%. After analyzing the data, Tamradhatu
      Shalaka was found to be more effective than Lauha and Panchadhatu Shalakas.

PMID- 22131719
TI  - Clinical evaluation of selected Yogic procedures in individuals with low back
      pain.
AB  - The present study has been conducted to evaluate selected yogic procedures on
      individuals with low back pain. The understanding of back pain as one of the
      commonest clinical presentations during clinical practice made the path to the
      present study. It has also been calculated that more than three-quarters of the
      world's population experience back pain at some time in their lives. Twelve
      patients were selected and randomly divided into two groups, viz., group A yogic
      group and group B control group. Advice for life style and diet was given for all
      the patients. The effect of the therapy was assessed subjectively and
      objectively. Particular scores drawn for yogic group and control group were
      individually analyzed before and after treatment and the values were compared
      using standard statistical protocols. Yogic intervention revealed 79% relief in
      both subjective and objective parameters (i.e., 7 out of 14 parameters showed
      statistically highly significant P < 0.01 results, while 4 showed significant
      results P < 0.05). Comparative effect of yogic group and control group showed 79%
      relief in both subjective and objective parameters. (i.e., total 6 out of 14
      parameters showed statistically highly significant (P < 0.01) results, while 5
      showed significant results (P < 0.05).

PMID- 22131720
TI  - Analytical study of Kuberaksha/Kantaki Karanja Patra Churna [Caesalpinia Bonduc
      (L.) Roxb. leaf powder].
AB  - Caesalpinia bonduc (L.) Roxb. (Kuberaksha) is an Ayurvedic herb used in the
      management of malaria, liver disorders, worms, edematous conditions, etc. Based
      on classical Ayurvedic textual indications and recent pharmacological studies,
      its leaf powder was selected for studying its effect clinically on filaria.
      Before conducting the clinical trails, this leaf powder was subjected to certain
      chemical studies to find the pH, ash value, extractive values, High Performance
      Thin Layer Chromatography (HPTLC), etc. for standardization of the drug.

PMID- 22131721
TI  - Standard manufacturing procedure for syrup and tablet forms of Jwarahara
      Dashemani.
AB  - Jwarahara Dashemani (JHD) is mentioned by Acharya Charaka under the different
      categories of Mahakashayas (groups of drugs having similar pharmacological
      actions). For the present study, syrup and tablet forms of JHDs were prepared and
      analyzed. The formulations were prepared in various batches by following the
      standard manufacturing procedure (SMP). JHD Kwatha (2200 ml) and 1430 g sugar
      candy powder were heated (80-90 degrees C) together for 3.10 hours and 2200 ml
      syrup was obtained, whereas an average of 446 g of tablet was obtained from the
      mixture of 285 g Ghana and powder of sugar candy (125 g), JHD Dravyas (55 g) and
      talc (18 g). These formulations were subjected to various analytical parameters
      and the results were observed on the basis of preparation.

PMID- 22131722
TI  - Evaluation of antimicrobial activity of Rasaka Bhasma.
AB  - Rasaka, one among the Maharasas, has been indicated in various diseases like
      Netrarogas, Prameha, etc. Lately, the use of Rasaka bhasma has been declined as
      an identification of Rasaka. The present study aims to prepare Rasaka bhasma from
      two different samples of Rasaka and undertake comparative antimicrobial activity
      study against Gram-positive and Gram-negative organisms by agar disk diffusion
      method.

PMID- 22131723
TI  - A comparative study on growth pattern of Langali (Gloriosa superba Linn.) under
      wild and cultivated conditions.
AB  - Langali (Gloriosa superba Linn.), obtained from wild habitat and by experimental
      cultivation under three groups, viz., control, cultivated as per the modern
      agricultural guidelines and as per the norms of Vriksha-ayurveda was compared and
      analyzed. Methods of Vriksha-ayurveda give good result in the case of Langali in
      terms of yield. Failure of control groups both in seed and tuber batches denotes
      that this plant needs some treatment for vegetative propagation under artificial
      conditions. Ayurveda group may be considered as a better one in the assessment of
      reproduction capacity in terms of yield of seeds.

PMID- 22131724
TI  - Editorial.

PMID- 22131725
TI  - A clinical trial of Sri Lankan traditional decoction of Pitawakka Navaya in the
      treatment of Kaphaja Shirsha Shoola.
AB  - Authentic Ayurvedic texts mention 11 types of Shiro Roga (diseases in the head).
      Kaphaja Shirsha Shoola, which occurs due to vitiation of Kapha and Vata Dosha, is
      one of them. Chronic sinusitis is a chronic inflammation of the sinuses. It can
      be correlated with Kaphaja Shirsha Shoola. Decoction of Pitawakka Navaya consists
      of nine ingredients; these are: Bhoomyamalaka, Haritaki, Barangi, Chavya,
      Pippali, Salarka, Guduchi, Shunthi and Maricha. These herbs, which pacify
      vitiated Vata Dosha and Kapha Dosha, are used by traditional physicians in Sri
      Lanka to treat Kaphaja Shirsha Shoola (chronic sinusitis). However, no scientific
      studies have been conducted to evaluate the efficacy of Pitawakka Navaya in the
      treatment of Kaphaja Shirsha Shoola. Hence, this clinical study was conducted to
      evaluate the efficacy of the decoction of Pitawakka Navaya in the treatment of
      Kaphaja Shirsha Shoola. Sixty patients suffering from Kaphaja Shirsha Shoola were
      selected and examined. These patients were randomly divided into two groups of 30
      patients each. The first group was treated with 120 ml of decoction of Pitawakka
      Navaya twice a day for 14 days. The second group was treated with 120 ml of
      placebo twice a day for 14 days. After treatment, most of the patients' symptoms
      were completely or partially relieved. In <10% of the patients, some symptoms
      were unchanged or aggravated. It is observed that the traditional decoction
      Pitawakka Navaya is beneficial for Kaphaja Shirsha Shoola (chronic sinusitis).

PMID- 22131726
TI  - Clinical study on erectile dysfunction in diabetic and non-diabetic subjects and
      its management with Ficus relegiosa Linn.
AB  - Healthy sexual functioning plays an essential role in maintaining the harmony and
      happiness in marital life. It provides a media to express love, which is the base
      for all sorts of creative activities. The absence of this function hampers the
      marital relationship, leading to frustration and, sometimes, ending in divorce,
      and causes inadequacy in performing the routine duties. In this study, 53
      patients having diabetes mellitus were surveyed to find out the incidence of
      erectile dysfunction (ED). Considering the high prevalence of the disease and the
      need to look for alternative medicine, a clinical trial on 44 patients of ED was
      carried out. These patients were divided into two main groups: diabetic and non
      diabetic, and were further divided into two subgroups as trial group and placebo
      group. In the trial group, Ashvattha Kshirpaka prepared with 10 g powder of its
      root bark, stem bark, fruit and tender leaf buds was given twice a day. In both
      the diabetic and the non-diabetic subjects, Ashvattha provided encouraging
      results on ED as well as on seminal parameters in comparison to the placebo.

PMID- 22131727
TI  - Clinical efficacy of Rasona Pinda in the management of Amavata (rheumatoid
      arthritis).
AB  - In the present clinical study, 63 patients of Amavata were registered from the
      Kayachikitsa out patient department/indoor patient department (OPD/IPD) of Sir
      Sunder Lal Hospital (Indian Medicine Wing), IMS, BHU, Varanasi-5. In group I
      (Rasona Pinda), 27 patients completed the study of a total of 33patients
      registered in the group (six patients dropped out mid-therapy). In group II
      (control group), 23 patients completed all three follow-ups out of 30 patients
      (there were seven dropouts in mid-therapy). In group I, complete remission in
      29.6%, major improvement in 59.3% and minor improvement in change font so as to
      appear 11.1% were observed. In group II, complete remission in 13%, major
      improvement in 21.7%, minor improvement in 39.1% and unchanged in 26.9% of the
      patients were observed.

PMID- 22131728
TI  - Randomized placebo-controlled trial of Mustadi Ghanavati in hyperlipidemia.
AB  - Hyperlipidemia is one of the major lifestyle disorders. Its role has been
      appreciated in the manifestation of serious diseases like ischemic heart disease,
      diabetes, stroke etc. These lifestyle diseases are a result of lifestyle factors
      such as overnutrition etc., which have been referred to as the Santarpanjanya
      Vyadhis in the classical texts. Mustadi Ghanavti is a modified form of the
      classical formulation Mustadi Kwath that has been advocated by Acharya Charaka
      for the management of Santarpanjanya Vikaras. This placebo-controlled randomized
      trial of Mustadi Ghanavati was carried out on 61 patients suffering from
      hyperlipidemia; of the 61 patients, 50 completed the entire course of treatment.
      The results of the study revealed that Mustadi Ghanavati decreased serum
      cholesterol by 22.4%, serum triglycerides by 19.6%, serum LDL by 18.2%, and serum
      VLDL by 4.2%; serum HDL increased by 5.6%. Thus Mustadi Ghanavati was able to
      effect a total improvement of 58.8% in the lipid profile. It brought about mild
      improvement in 42.86% of patients and moderate improvement in 14.28% of patients.
      Mustadi Ghanavati was also found to have a significant effect on other subjective
      as well as objective parameters considered for the study.

PMID- 22131729
TI  - Evaluation of the role of Nithyavirechana and Nayopayam kashaya in Tamaka Shwasa.
AB  - Man has been in steady attempt to find the solutions for the life-threatening and
      distressing disorders, which afflict the human race. One of such condition is
      "Tamaka Shwasa," which is recognized by the name bronchial asthma in contemporary
      discipline, wherein episodic attacks are the characteristic features, leaving the
      patient in pathetic situation. Therefore management of this acute respiratory
      condition is the long mission in the medical society of all types. There is
      abundance of medicines explained for Tamaka Shwasa in Ayurveda, and it is
      mentioned that combined Shodhana and Shamana therapy is more effective. Hence the
      present study is designed to evaluate the role of Nithyavirechana followed by
      Shamana in the form of Nayopayam kashaya in patients of Tamaka Shwasa. This was a
      single blind clinical study with pre-test and post-test design where in 20
      patients suffering from Tamaka Shwasa of either sex between the age group of 16
      and 60 years were subjected to the trial. These patients were treated with
      Nithyavirechana with Eranda thaila (castor oil) followed by oral administration
      of Nayopayam kashaya in a dose of 50 ml twice a day. The therapeutic effect of
      the treatment was assessed based on specific subjective and objective parameters.
      Results obtained were analyzed for the statistical significance by adapting
      paired 't' test. Statistical analysis established that Eranda thaila and
      Nayopayam kashaya are highly effective in counteracting the symptoms of Tamaka
      Shwasa.

PMID- 22131730
TI  - A comparative clinical study of Nyagrodhadi Ghanavati and Virechana Karma in the
      management of Madhumeha.
AB  - Diabetes mellitus is a common chronic metabolic disorder prevalent all over the
      world. Virechana is the Shodhana procedure that is specific for the elimination
      of vitiated Pitta and Kapha doshas. Thus, in the present study, the Virechana
      process has been selected prior to the administration of Shamana drug.
      Nyagrodhadi churna is mentioned in Chakradatta, which is modified into Ghana form
      for easy administration and dose maintenance. The present study was conducted in
      two groups: Group A, Nyogrodhadi Ghana vati (Shamana therapy) and Group B,
      Virechana and Nyogrodhadi Ghana vati (combined therapy). A total of 42 patients
      were registered for the present study, in which 34 patients completed the and
      eight patients were dropouts. After evaluating the total effect of the therapies,
      it was observed that the Virechana and Nyagrodhadi Ghanavati (combined therapy)
      provided better relief in the patients of Madhumeha in comparison with
      Nyagrodhadi Ghanavati (Shamana therapy) alone.

PMID- 22131731
TI  - A comparative study of Dashamoola Taila Matra Basti and Tila Taila Matra Basti in
      Kashtartava (dysmenorrhea).
AB  - Kashtartava is a broad term which covers all the problems and ailments that a
      woman may suffer from during or around menstruation. It includes both primary and
      secondary types of dysmenorrhea. For this study, however, we considered only
      primary dysmenorrhea under the term Kashtartava to cover a larger population and
      to make a pin-pointed assessment criteria. Thus, 40 patients in the age-group of
      15-25 years suffering from primary dysmenorrhea were registered for the study. Of
      these patients, 35 completed the course of treatment. The selected patients were
      randomly allotted into two groups. Group A received Dashamoola Taila Matra Basti
      and group B received Tila Taila Matra Basti. These treatments were selected for
      the Vatashamaka, Yonishula Prashaman, and Shothahara properties of the drugs. The
      dose was 60 ml per day and the duration of treatment was for 7 days each cycle
      for two consecutive cycles. Results were assessed according to a specially
      prepared grading system for pain, Alpartava, Yatochitkaladarshana, Praseka,
      Chhardi, Vibandha, Shrama, Atisara, Vankshana, Kati, Janu Shula, Shiroshula,
      Swedadhikya, and Tamodarshana. Significant improvement was seen in symptoms in
      both groups, and on comparing the results in the two groups we found that the
      results were almost equivalent. There was complete remission of symptoms in
      38.89% in group A and in 35.39% in group B, while there was marked improvement in
      50% in group A and 47.65% in group B. However, there was a marked difference
      between the two groups with regard to recurrence of symptoms during the follow-up
      period of 2 months, with recurrence being significantly more in group B. The
      study suggests that Matra Basti can be a reliable treatment for relieving the
      symptoms of primary dysmenorrhea. We recommend that more research be done to
      confirm the findings of this study.

PMID- 22131732
TI  - An assessment of Manasika Bhavas in menopausal syndrome and its management.
AB  - The present clinical trial was conducted to evaluate the efficacy of Shirodhara
      and Saraswatarishta as compared to hormone replacement therapy (HRT) in the
      management of menopausal syndrome, along with the assessment of Manasika Bhavas.
      The subjects were randomly divided into three groups. A total 48 patients were
      selected for the study, out of which 43 patients completed the study. Specialized
      Ayurvedic rating scales like Manasa Pariksha Bhavas as well as the Hamilton
      Anxiety Rating Scale, Hamilton Depression Rating scale, and Menopause Rating
      Scale were adopted to assess the effect of therapy. The effects were examined on
      the chief complaints as well as the associated complaints. Patients undergoing
      Shirodhara had better relief of the disturbances of Manasa Bhavas and psychic
      symptoms of menopause as compared to the other two groups. Saraswatarishta also
      showed encouraging results in managing the associated somatic symptoms and the
      psychic symptoms. Hence, we conclude that it can be used as an alternative
      therapy to HRT.

PMID- 22131733
TI  - Effect of Vasantic Vaman and other Panchakarma procedures on disorders of various
      systems.
AB  - Kapha is dominant and vitiated in Vasant ritu as it is described in Ayurveda.
      Acharya Chakrapani has said in chapter six, that not only Vaman, but all the five
      biopurification methods of the Panchakarma should be practiced in Vasant ritu.
      Out of the two best seasons in a year for purification, Vasant is better one.
      This pilot research study was carried out to see the effect of this
      biopurification process on different disorders. The results were marvelous, as
      symptomatically 58% relief was achieved.

PMID- 22131734
TI  - Role of Pradhamana Nasya and Trayodashanga Kwatha in the management of Dushta
      Pratishyaya with special reference to chronic sinusitis.
AB  - Dushta Pratishyaya is the chronic stage of Pratishyaya, which occurs due to
      neglect or improper management of the disease Pratishyaya. In modern science,
      chronic sinusitis can be correlated with Dushta Pratishyaya on the basis of the
      signs, symptoms, complications, and prognosis. Changing lifestyles, rapid
      urbanization, and the increase in cases of antibiotic resistance are responsible
      for the rise in the prevalence of sinusitis. In the present clinical study, 37
      patients were registered and were randomly divided into three groups: A, B, and
      C; of the 37 patients, 31 completed the full course of treatment. In group A,
      Trayodashanga Kwatha with Madhu was given orally; in group B, Pradhamana Nasya
      with Trikatu + Triphala Churna was administered; and in group C (combined group),
      Pradhamana Nasya was administered initially, followed by oral Trayodashanga
      Kwatha with Madhu. In group A, complete relief was observed in 10% of the
      patients; in group B, marked improvement was observed in 81.82% of patients; and
      in group C, marked relief was observed in 60% of patients. In comparison to other
      groups (Group A and Group B), Group C showed percentage wise better results in
      most of the symptoms.

PMID- 22131735
TI  - Effect of Mahayavanala Roma Kshara and Dhanyaka Gokshura Ghrita in benign
      prostatic hyperplasia.
AB  - Vatastheela is a disease of Mutravahasrotasa, one among the 12 types of
      Mutraghata disorders elaborated by Sushruta in his seminal work, the Sushruta
      Samhita. Vatastheela, as described in Ayurveda, closely resembles benign
      prostatic hyperplasia (BPH) of modern medicine in its signs and symptoms. It is a
      senile disorder and chiefly affects individuals above the age of 40 years. The
      symptoms are those of bladder outflow obstruction, with increased frequency of
      micturition, dribbling, hesitancy, and the features of chronic urinary retention.
      Surgical management has been accepted as the standard management but is
      associated with many disadvantages as well as complications, which may not be
      acceptable at this age. Conservative management with modern medicines is also not
      free from side effects. So, in this age-group, there is a need for much safer
      alternative method of management. In this regard, many works have been carried
      out and shown that the Ayurvedic approach, using natural medicines, is a far
      better approach. We carried out a comparative study of Mahayavanala Roma Kshara
      (MRK) and Dhanyaka Gokshura Ghrita (DGG), which are the compounds prescribed for
      Mutraghata in Ayurvedic literature. The patients were randomly selected from the
      OPD and IPD of IPGT and RA hospital, Jamnagar, Gujarat, and divided into two
      groups. In first group, one (500 mg) capsule of MRK was given twice a day with
      lukewarm water for 45 days; in second group, 10 gm of DGG was given orally twice
      a day with lukewarm water for 45 days. DGG showed significantly greater relief in
      the subjective parameters as per International Prostate Symptoms Score (IPSS)
      than MRK. However, reduction in the size of the prostate and in the volume of the
      post-void residual urine was found much better in the MRK group.

PMID- 22131736
TI  - Ayurvedic approach for improving reaction time of attention deficit hyperactivity
      disorder affected children.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a behavioral disorder of
      children. It is the most common neurological disorder of childhood. The present
      study was conducted to examine the increase in attention span in 43 ADHD-affected
      children treated with different approaches. The reaction time was measured using
      a Vernier chronoscope (electronic). Selected children of both sexes in the age
      group of 6-16 years were divided into three groups. In group A, 17 patients
      received syrup Ayurvedic compound I; in group B, 14 patients were treated with
      syrup Ayurvedic compound I + Shirodhara with milk; and in group C, 12 patients
      received syrup Ayurvedic compound II (placebo). The dose of the drug was 1.0
      ml/kg body weight and the duration of treatment was 3 months. Group B showed
      highly significant (P<.001) improvement in total reaction time, while in group C
      the change was statistically nonsignificant P > 0.10. It was found that while the
      drug and Shirodhara were both effective in improving the reaction time of ADHD
      affected children, the drug combined with Shirodhara was superior to the drug
      used alone.

PMID- 22131737
TI  - Clinical effect of Matra Basti and Vatari Guggulu in the management of Amavata
      (rheumatoid arthritis).
AB  - Amavata is the most crippling of the joint diseases. It occurs throughout the
      world in all climates and all ethnic groups. Though all the Doshas take part in
      the causation of this disease, Ama and vitiated Vata play the dominant role. The
      clinical features of rheumatoid arthritis, such as pain, swelling, stiffness,
      fever, and general debility, are almost identical to that of Amavata. Treatment
      provides symptomatic relief, but the underlying pathology remains unchecked
      because of the absence of effective drugs. In the management of Amavata all the
      acharyas have described the sequential employment of Dipana, Amapachan, Shodhan,
      and Shaman therapies. For this study, 118 patients of Amavata were randomly
      divided into two groups. The patients in group A (50 patients) were given Matra
      Basti with Brihat Saindhavadi Taila along with Vatari Guggulu; the patients in
      group B (53 patients) were given only Vatari Guggulu. All the patients responded
      favorably to the treatment in both the groups; however, patients treated with
      Matra Basti had better relief in most of the cardinal signs and symptoms of the
      disease.

PMID- 22131738
TI  - Comparative study of Upavasa and Upavasa with Pachana in the management of
      Agnisada.
AB  - Ayurvedic management is not only concerned with the cure of the diseased person,
      but is also meant to maintain the health of the healthy person because it is used
      for Dhatusamya. Langhana is the prime tool in the process of Dhatusamya. In this
      research study, Upavasa plus Pachana and Upavasa (among ten types of Langhanas)
      are applied in two different groups, using the random sampling method. Upavasa is
      taken as Hina Matra Bhojana - that is, gradually increasing the dose of Ahara (by
      Padanshika Krama) was applied on the basis of the Ahara Shakti of the Atura and
      status of the Agnisada. Furthermore, for the Pachana, Shunthi (Zingiber
      officinale) was selected. The subjects for the study were patients who had signs
      and symptoms of Agnisada and were between the age group of 20 and 60 years. In
      Group A (Upavasa plus Pachana) 83.77% and in Group B (Upavasa) 72.97% improvement
      was found, which was statistically highly significant (< 0.001). Upavasa plus
      Pachana and Upavasa were both found beneficial in promoting the Agni in patients
      with Agnisada. However, in the percentage-wise comparison Group A showed better
      result than Group B.

PMID- 22131739
TI  - A clinical study of Ashwagandha ghrita and Ashwagandha granules for its Brumhana
      and Balya effect.
AB  - Good nutrition is the cornerstone of long life, good health, and proper
      development. Well-nourished children perform well in school, grow into healthy
      adults and, in turn, give their children a better start in life. Malnutrition,
      however, continues to be a significant problem, especially among children who can
      not fend adequately for themselves. Either due to various diseases or due to
      excessive indulgence in Karshyakara Nidanas pathological changes occur in the
      body, leading to manifestation of Karshya; in such situations, Brumhana therapy
      is indicated. This study was planned to evaluate the drug Ashwagandha for its
      Brumhana effect in children. A total 121 children were enrolled in the study, of
      which 111 completed the full course of treatment. The children were randomly
      separated into three groups;, groups A (Ashwagandha ghrita), B (Ashwagandha
      granules), and C (Placebo). The improvement was maximum in group A, i.e., the
      subjects receiving Ashwagandha Ghrita. However, childhood is a period of growth
      and therefore all the children responded to the therapy to some extent. There was
      good relief of the chief complaints and a trend for improvement was seen in
      supplementary parameters also.

PMID- 22131740
TI  - Urolithic property of Varuna (Crataeva nurvala): An experimental study.
AB  - Despite modern techniques, the recurrence rate of Urolithiasis is approximately
      50% within 5 years. Thus, there must be some drug that corrects the metabolic
      errors and prevents the formation of stone. In Ayurveda, a detailed description
      of urolithiasis is mentioned under the heading of Ashmari. A group of Ayurvedic
      drugs are described for the management of Urolithiasis, like Pashanbheda
      (Bergenia ligulata), Varuna (Crataeva nurvala), Kullattha (Dolichos biflorus),
      Gokshur (Tribulus terrestris), etc. in our ancient texts. The present work was
      designed to study the effect of Varuna (Crataeva nurvala) on the experimental
      model of urolithiasis (albino rats). The study was categorized into two groups:
      Group I, treated and Group II, control. In all albino rats, stone was surgically
      implanted into the urinary bladder. Estimation of the urinary and serum
      electrolyte done periodically and x-rays were exposed at a regular interval. This
      study suggests the decoction of Varuna (Crataeva nurvala) is effective in the
      management of urolithiasis.

PMID- 22131741
TI  - Antipyretic activity of Guduchi Ghrita formulations in albino rats.
AB  - The present pharmacological investigation was undertaken to study the anti
      pyretic activity of Guduchi ghrita formulations in albino rats against yeast
      induced pyrexia. Seven groups of six animals were used for the experiment. The
      yeast induced pyrexia method was standardized first by injecting 12.5% yeast
      suspension (s.c) followed by recording the rectal temperature at regular
      intervals. Then the evaluation of anti-pyretic activity of Guduchi ghrita
      formulations was carried out by using this standard procedure. Both the Guduchi
      ghrita samples including vehicle significantly attenuated the raise in
      temperature after three hours of yeast injection. After 6 and 9 hours of yeast
      injection also both the Guduchi ghrita samples attenuated the raise in
      temperature in a highly significant manner in comparison to both yeast control
      and vehicle control groups. The data generated during study shows that both the
      Guduchi ghrita formulations having significant anti-pyretic activity.

PMID- 22131742
TI  - Analgesic effect of Lepidium sativum Linn. (Chandrashura) in experimental
      animals.
AB  - Lepidium sativum Linn, which is known as "Aselio" locally, is frequently used by
      the villagers for the treatment of Sandhivata (osteoarthritis), with good
      therapeutic relief. Here, we have to observe the analgesic activity of the seed
      of Lepidium sativum Linn in albino rats and Swiss albino mice with different
      parameters. The analgesic study was performed with acetic acid-induced writhing
      response in mice, formaldehyde-induced paw licking response in rats and tail
      flick response in mice. Experiments were carried out in two groups - therapeutic
      dose group and double dose group - with comparison with the control group. In the
      acetic acid-induced writhing syndrome, latency of onset was highly significantly
      increased in the therapeutic dose group and significant increase was found in the
      double dose group. In the formaldehyde-induced paw licking response, the test
      drug produced significant inhibition of neurogenic pain in the double dose group
      and significant inhibition of inflammatory pain in the therapeutic dose group. In
      the tail flick response, the test drug produced a mild to moderate effect in the
      therapeutic dose group and also in the double dose group.

PMID- 22131743
TI  - Botany, Taxonomy and Cytology of Crocus sativus series.
AB  - Saffron is produced from the dried styles of Crocus sativus L. (Iridaceae) which
      is unknown as wild plant, representing a sterile triploid. These belong to
      subgenus Crocus series Crocus sativus - series are closely related species; and
      are difficult to be separated taxonomically and have a complex cytology. Botany
      of C. sativus - series, taxonomy of their species and their infraspecific taxa
      are presented, and their distribution, ecology and phenology; full description
      and chromosome counts are provided with key to their identification.

PMID- 22131744
TI  - Impact of Bhavana Samskara on physico-chemical parameters with special reference
      to Gandhaka Rasayana prepared by different media and methods.
AB  - Gandhaka Rasayana is frequently used in the management of different skin
      disorders (Kushtha). It is a herbo-mineral preparation prepared by Shuddha
      Gandhaka Bhavit with 11 herbal drugs in a serial manner for eight times each.
      Therefore, it was used as a model drug and four samples were prepared by adopting
      different methods and media. The physicochemical parameters were evaluated. The
      effect of increasing the number of Bhavana (lavigation) on particle size of the
      drug was examined. Similarly, an attempt was also made to differntiate the
      structure (surface anatomy) of the drug with Bhavana and without Bhavana by using
      a very sophisticated x-ray photo electron spectrometer (XPS) study. Overall, a
      remarkable difference was observed in the samples with Bhavana and without
      Bhavana.

PMID- 22131745
TI  - Pharmaceutical study of Lauha Bhasma.
AB  - In the present research paper, the work done on pharmaceutical study of Lauha
      Bhasma conducted in the Department of Rasa Shastra under the postgraduate
      research programme is being presented. The pharmaceutical processing of Lauha
      Bhasma was performed by following samanya shodhana, vishesha shodhana and marana
      of Lauha. Under the process of marana, three specific pharmaceutical techniques
      were followed, viz. bhanupaka, sthalipaka and putapaka. During the putapaka
      process, an electric muffle furnace (EMF) was used. The temperature of puta was
      studied in two batches, viz. in Batch I, a temperature of 800 degrees C was
      maintained whereas in Batch II, a temperature of 600 degrees C was maintained.
      The purpose behind selecting two temperatures was to validate the process of
      marana of Lauha and to determine an ideal temperature for the preparation of
      Lauha Bhasma in EMF. It is found that after 20 puta at a temperature of 600
      degrees C, the Lauha Bhasma was prepared properly. The entire characteristic of
      Lauha Bhasma, like "pakwa jambu phala varna," varitar, etc. was attained at 600
      degrees . At a temperature of 800 degrees C, the process could not be carried out
      smoothly. The pellets turned very hard and brassy yellow in color. The desired
      color was attained only after decreasing the temperature in further puta.

PMID- 22131746
TI  - Role of media in the preparation of Apamarga Ksharataila.
AB  - Generally, Tailas and Ghritas have been prepared by using Kalka (paste) and Drava
      dravya (liquid media usually SwaRasa or Kwatha). However, Apamarga Kshara taila
      is prepared by using Apamarga Kshara drava (the alkali is obtained after
      dissolving it in water, after obtaining it by burning, dissolving, and filtration
      of the same plant). Therefore, to evaluate the role of the media during the
      preparation, the Taila was prepared in different samples by using the fresh and
      dry paste of Apamarga along with SwaRasa and Kwatha of Apamarga. All the samples
      were tested through various analytical parameters, that is, pH, acid value,
      iodine value, saponification value, and soon. Finally, it was found that Apamarga
      Kshara taila prepared by using fresh Kalka and Ksharajala was better and it was
      also an easy pharmaceutical procedure.

PMID- 22131747
TI  - Physiological aspects of Agni.
AB  - Agni is the invariable agent in the process of Paka (digestion, transformation).
      Ingested food is to be digested, absorbed and assimilated, which is unavoidable
      for the maintenance of life, and is performed by the Agni. Different examples are
      available in our classics to indicate that Pitta is the same as Agni, but some
      doubt arises behind this concept, that Pitta is Agni. Agni is innumerable because
      of its presence in each and every paramanu of the body. But, the enumeration of
      the number of Agni varies in various classical Ayurvedic texts. According to the
      functions and site of action, Agni has been divided into 13 types, i.e. one
      Jatharagni, five Bhutagni and seven Dhatvagni. Jatharagni is the most important
      one, which digests four types of food and transforms it into Rasa and Mala. The
      five Bhutagnis act on the respective bhutika portion of the food and thereby
      nourish the Bhutas in the body. The seven Dhatvagni act on the respective dhatus
      by which each Dhatu is broken into three parts. In this way, the entire process
      of transformation consists of two types of products - PRasad (essence) and Kitta
      (excrete). The former is taken for nourishment while the latter one is thrown
      out, which otherwise defiles the body if it stays longer.

PMID- 22131748
TI  - Thirst areas of research in Ayurveda.

PMID- 22131750
TI  - AYU: The unique platform for Ayurvedists.

PMID- 22131749
TI  - Need of new research methodology for Ayurveda.

PMID- 22131751
TI  - Symbiohealth - Need of the hour.
AB  - A SYMBIOTIC RELATIONSHIP BETWEEN ALLOPATHY (MODERN MEDICINE) AND AYURVEDA IS
      FUNDAMENTAL IN CREATING A HEALTH CARE SYSTEM THAT IS : (a) more effective than
      either system used alone, (b) less expensive, (c) less toxic and (d) more likely
      to create a healthier society. The fundamental basis of Allopathy is "offense
      thinking," corresponding to Newton's physics, which makes it an excellent disease
      management system; on the other hand, Ayurveda is based upon "defense thinking"
      and corresponds to Quantum physics, and is an excellent system for prevention of
      disease and for protection and rejuvenation of health. A judicious use of the two
      systems in group practice will provide better care to the masses.

PMID- 22131752
TI  - Understanding personality from Ayurvedic perspective for psychological
      assessment: A case.
AB  - The study of personality has fascinated psychologists since a long time.
      Personality as an area of study has grown so much that a wealth of literature is
      available. On the other hand, the socio-ethnic dynamics of human race in the
      emerging global village context provoking psychologists to develop a personality
      theory which can treat certain basic components of personality as invariants, so
      that irrespective of culture, race, and nativity could still be able to study
      personality which will have universal applicability and relevance, is still far
      away. In the above emerging backdrop, "Ayurveda" has perhaps an important role to
      play as it can enable providing a theoretical and empirical base of personality
      traits and types. These Ayurvedic concepts are applicable to all human beings
      irrespective of caste, color, sex or race. Therefore, it is interesting to build
      on the Ayurvedic knowledge which has already given us so much since time
      immemorial, and validate some of these issues related to personality from
      psychological perspective. There are already certain efforts in understanding
      Sattva, Rajas, and Tamas Gunas. It can be furthered so that a comprehensive
      personality picture can be generated, which can have implications for health,
      career, education and many other dimensions of life. The present paper is a
      theoretical attempt in developing such a personality proposition which can be
      validated. Thus, the present paper only builds a theoretical framework for their
      possible empirical validity.

PMID- 22131753
TI  - A review on role of prakriti in aging.
AB  - Ayurveda is an eternal science with absolute principles, and prakriti is one of
      these. It plays an important role in the selection and establishment of every
      factor for which a person is going to interact from conception till death, e.g.
      lifestyle, diet planning, etc. Prakriti stands for nature of the body in terms of
      dosha and is decided at the time of conception according to the predominance of
      dosha. It does not change during the whole life and is responsible for the
      physical and mental characteristics of an individual. This prakriti is of seven
      types according to tridosha. The individuals of specific prakriti exhibit
      biological variations in terms of structure, function, behavior, individual
      response to internal and external environmental stimuli, susceptibility to
      different diseases, etc. Aging is a process of decaying and included in natural
      diseases. In our body, Pitta or Agni is responsible for the various types of
      pathological conditions. Although aging is a natural pathological condition,
      Pitta plays an important role in its causation like other pathological
      conditions. It is clearly indicated in Charak samhita that persons having Pitta
      predominance personality tend to suffer early with decaying process and other
      changes of aging. Through this article, we have made an attempt to reevaluate the
      interrelationships between prakriti and aging.

PMID- 22131754
TI  - Clinical study on the efficacy of Chandra Kalka with Mahadalu Anupanaya in the
      management of Pakshaghata (Hemiplegia).
AB  - Hemiplegia is a highly prevalent disease and can be correlated with Pakshaghata,
      a disease described in Ayurveda. In Sri-Lankan traditional system of medicine,
      Chandra Kalka with Mahadalu Anupanaya are used successfully in the management of
      early stage of Pakshaghata and mentioned in Vatika Prakaranaya, a book on
      traditional medicine. So far, no scientific studies have been performed to
      evaluate the efficacy of Chandra Kalka with Mahadalu Anupanaya. This study was
      conducted at Kurunegala Ayurvedic Base Hospital, Sri-Lanka. Thirty patients were
      selected and randomly divided into two groups. The first group consisted of
      twenty five patients and treated with one pill of (250 mg) Chandra Kalka with 40
      ml of Mahadalu Anupanaya three times a day for fourteen days as an internal
      therapy. Second group consisted of five patients who were treated with placebo in
      single blind method. The response to the treatment was recorded and therapeutic
      effect was evaluated through symptomatic relief of the patients. In the group of
      patients treated with the above drugs, statistically significant reduction was
      observed in symptoms such as slurring of speech, swallowing difficulties,
      fasciculation of tongue, and mouth deviation. In view of this observation and
      results obtained in this study, it is concluded that the above drug is a very
      effective traditional preparation that could be used in early stage of management
      of Pakshaghata, providing speedily and positive effects with a powerful action in
      controlling symptoms of Pakshaghata.

PMID- 22131755
TI  - Clinical efficacy of Mehamudgara vati in type 2 diabetes mellitus.
AB  - In type 2 diabetes, insulin resistance is the main problem that is associated
      with a cluster of conditions such as obesity and hyperlipidemia. The present
      study was designed with the objective to evaluate the role of Mehamudgara vati
      (MMV), which was expected to work at the level of Medodhatwagni due to its
      Medohara properties, to have an effective control on type 2 diabetes. To fulfill
      the objective, known patients of type 2 diabetes attending the OPD and IPD of
      Kayachikitsa Department, IPGT and RA, were selected and were divided in two
      groups. In Group A, MMV was given 3 tab. thrice a day with lukewarm water for 3
      months and in Group B, the patients who were already taking modern antidiabetic
      treatment, although their blood sugar level was not well under control, were
      additionally given MMV in the same manner. The formulation has shown a highly
      significant decrease in the fasting and post-prandial blood sugar level. The
      formulation has also shown a synergistic action when combined with the modern
      antidiabetic drugs due to its known hypolipidemic, hypocholesterolemic,
      hepatoprotective, antihyperglycemic, antistress, antioxidant and immunomodulatory
      activities.

PMID- 22131756
TI  - Observations on Vamana procedure in healthy volunteers.
AB  - Vamana Karma is one of the five Pradhana Karmas of Panchakarma which is
      successfully used in treating Kaphaj disorders. Panchakarma is also indicated in
      healthy states. (C.Su. 16/13-16) for Shodhana. Textual references are available
      in Ayurvedic classics, but the procedure needs to be validated in the modern
      times when Ahara Shakti, Bala and Agni of the individuals have decreased
      considerably. So the effect of procedure was observed in 30 healthy volunteers of
      age group 18 to 60 years. Lakshanik, Vaigiki, Maniki and Antiki Shuddhi were
      observed and vomitus was analyzed macroscopically, microscopically and
      chemically.

PMID- 22131757
TI  - A comparative study of Rasona Rasnadi Ghanavati and Simhanada Guggulu on Amavata
      with special reference to Rheumatoid arthritis.
AB  - The present study was aimed to assess the clinical effectiveness of Rasona
      Rasnadi Ghanavati and Simhanada Guggulu along with Rasona Rasnadi Lepa in
      Amavata, and to compare the effect of these two therapies in the treatment. Total
      101 patients of Amavata were registered for the present study and were randomly
      divided into two groups. In group A- Rasona Rasnadi Ghanavati 2 Vati thrice/day
      was given for 3 months, while in group B- Simhanada Guggulu 2 Vati thrice a day
      for 3 months was adminstered. Along with this, Rasona Rasnadi Lepa was applied
      locally over affected joints twice daily in both groups. The effects of therapy
      in both groups were assessed by a specially prepared proforma. The results of the
      study showed that both the groups showed significant relief in symptoms; however,
      compared to Simhanada Guggulu, Rasona Rasnadi Ghanavati showed better result in
      the management of Amavata. Simhanada Guggulu or Rasona Rasnadi Ghanavati along
      with Rasona Rasnadi Lepa can be used as an effective ayurvedic intervention in
      the treatment for rheumatoid arthritis.

PMID- 22131758
TI  - Effect of Ayurvedic management in 130 patients of diabetic nephropathy.
AB  - Diabetic nephropathy is a specific form of renal disease. It is a major cause of
      renal insufficiency and ultimately of death. The present study has been carried
      out to prove the efficacy of Ayurvedic drugs in the management of diabetic
      nephropathy, which can be helpful in reducing the need of dialysis and avoiding
      or delaying renal transplantation. A total of 130 patients of this disease were
      treated in IPD (Group A) and OPD (Group B). Ayurvedic formulations including
      Gokshuradi Guggulu, Bhumyamalaki, Vasa and Shilajatvadi Vati were given to all
      the patients for 2 months. Group A patients were given special planned food.
      Results were analyzed statistically using "t" test. In group A patients, highly
      significant reduction was found in the values of serum creatinine, blood urea and
      urinary excretion of albumin. Marked improvement was found in the patients'
      general physical well-being, together with reduction in symptoms, in group A
      patients. This shows the importance of Pathyapathya in Ayurvedic management of
      the disease. This management may bring some new hope to the patients of diabetic
      nephropathy, which usually terminates to chronic renal failure and ultimately to
      death. Further studies are being carried out in this regard.

PMID- 22131759
TI  - Clinical efficacy of Coleus forskohlii (Willd.) Briq. (Makandi) in hypertension
      of geriatric population.
AB  - Hypertension is the most common psychosomatic disorder affecting 972 million
      people worldwide. The present clinical study deals with the effect of Makandi
      (Coleus forskohlii (Willd.) Briq.) Ghana vati and tablets of its powder in
      hypertension found in the geriatric age group (50-80 years). A total of 49
      hypertensive patients fulfilling the diagnostic criteria were registered in two
      groups-Group I (Ghana vati) and Group II (Churna tablet). Out of 27 enrolled
      patients of group I, 21 patients completed the treatment. In Group II, out of 22
      registered patients, a total of 20 patients completed the treatment. The effect
      of the therapy was assessed on the basis of changes in the systolic and diastolic
      blood pressures, in both sitting and supine positions; with Manasa Bhava
      Pariksha, Manasa Vibhrama Pariksha, symptomatology, geriatric signs and symptoms,
      and a brief psychiatric rating scale. Analysis of the results showed that the
      treatment in both the groups had been found to be good. It can be stated that
      Makandi, either in Ghana vati form or in churna tablet form, is an effective
      remedy for the treatment of hypertension. On analyzing the overall effect, 76.19%
      patients in Group I and 75.00% patients in Group II were mildly improved.
      Comparatively the overall treatment with group I was found to be better.

PMID- 22131760
TI  - Clinical evaluation of the efficacy of Shvitrahara kashaya and lepa in vitiligo.
AB  - Vitiligo is a progressive, idiopathic, pigmentation disorder of the skin,
      characterized by hypopigmented white lesions. PUVA therapy is the treatment of
      choice in the modern system of medicine. In Ayurveda, Shvitra or Kilasa is the
      term employed to describe hypopigmentation disorders of the skin. Shvitra is
      caused by various dietic and behavioral factors which aggravate the tridoshas,
      especially the Kapha dosha vitiating the Meda dhatu. Many Ayurvedic drugs are
      well known for the regeneration of melanocytes, among which Bakuchi is one. The
      present study was planned to study its efficacy in the regeneration of
      melanocytes. The outcome of treatment in 50 cases of Shvitra vis-a-vis vitiligo
      receiving Shvitrahara kashaya and Shvitrahara lepa was analyzed and compared.
      Group I (n = 25) patients were treated with Shvitrahara kashaya and Shvitrahara
      lepa; Group II (n = 15) patients received Shvitrahara lepa only; and the
      remaining 10 patients of Group III used both (Western medicine) oral psoralens
      and UV-A therapy. Assessment was done after 6 months with bi-monthly follow-ups.
      Out of 25 cases in Group I, 17 showed 80% improvement (t = 7.65; P < 0.01) in the
      surface area, number of lesions, pigmentation and associated symptoms like
      itching; out of 15 patients in Group II, 10 showed partial repigmentation, i.e.
      50% (t = 5.72; P < 0.01) response was observed. In Group III, 90% response (t =
      6.14; P < 0.001) in repigmentation and number of lesions as well was noted but
      eight patients developed adverse effects like sunburn, severe itching and gastric
      upset on taking oral psoralen. On the basis of results and observations, it can
      be concluded that Ayurvedic formulation containing Bakuchi is efficacious and has
      no untoward effects when compared to oral psoralens and UV-A therapy.

PMID- 22131761
TI  - A clinical study of Panchakola Siddha Yavagu in the management of Agnimandya.
AB  - This research is carried out with the aim to study Agnidipana effect of
      Panchakola Siddha Yavagu which comprises Pippali (Piper longum), Pippalimula
      (root of Piper longum), Chavya (Piper chaba Hunter), Chitraka (Plumbago zelynica)
      and Nagara (Zingiber officinale) which are all in equal proportion processed in
      six times of water. A randomized open clinical trial on 47 patients of Agnimandya
      has been screened on the basis of clinical findings and the patients were
      allocated to two groups. Group A having 29 cases received the trial drug
      (Panchakola Siddha Yavagu) and 18 cases in Group B received simple Yavagu with
      roasted rice powder as the control group. Special scoring pattern was done for
      the assessment of Agnimandya state. Complete cure of the patient was found in
      17.24% of the patients, 34.48% patients were improved moderately as well as
      markedly, whereas mild improvement was observed in 13.80% patients by treatment
      with Panchakola Yavagu.

PMID- 22131762
TI  - A study on Tailabindu pariksha - An ancient Ayurvedic method of urine examination
      as a diagnostic and prognostic tool.
AB  - Indian traditional medicine, Ayurveda has a great history. Researchers in India
      have tried to corroborate ancient wisdom with the modern scientific practices.
      Tailabindu pariksha is a diagnostic tool of urine examination developed by the
      medieval Ayurvedic scholars, and also throws a light on the prognosis of the
      disease condition. This study aims at using this ancient wisdom to diagnose the
      medical conditions and to study about their prognosis, and studying about how it
      can be applied to modern medical practice and its limitations. For the purpose of
      the study, 30 volunteers were divided into 3 groups. Group I consisting of
      healthy volunteers, group II of those patients who suffer from curable conditions
      and group III consisting of patients suffering from chronic diseases which can be
      regarded as incurable. The urine collection, oil drop instillation and
      evaluation, were all done according to the guidelines laid down in Ayurvedic
      practices. Upon the evaluation of the color, appearance, consistency and pattern
      of oil drop spreading in different patients of different groups, it could be seen
      that the data could be correlated to what has been provided in the literature in
      majority of the cases. In today's modern medical practices, there is a plethora
      of urine diagnostic examinations available. These act as an added financial
      burden to the patients. In the midst of this, making use of Tailabindu pariksha
      for urine examination, will not only prove economical, but also is a time-tested
      and scientifically proven method. More in-depth studies on larger groups of
      patients, suffering from various diseases need to be done to standardize the
      procedure and make it scientifically more acceptable.

PMID- 22131763
TI  - A comparative study on efficacy of Bharangyadi Avaleha and Vasa Avaleha in the
      management of Tamaka Shwasa with reference to childhood asthma.
AB  - Ayurvedic concept is of the opinion that Tamaka Shwasa (Bronchial Asthma) is a
      Yapya Vyadhi. The etiopathogenesis, signs, and symptoms of Tamaka Shwasa may be
      correlated with Bronchial Asthma. Each child reacts differently to the factors
      that trigger asthma and treated symptomatically. Asthma is the most common
      chronic allergic disorder in childhood and third leading cause of hospitalization
      under the age of 15 years. As it is a Kapha-Vata predominant disorder, Ayurvedic
      medicine may help to decrease the recurrence, improve immunity, and check
      symptoms naturally. With this aim, a clinical study was undertaken on two groups
      for duration of 6 weeks. The drugs Bharangyadi Avaleha and Vasa Avaleha were
      given orally, separately in both the groups. All the patients were kept under
      strict dietary control during the treatment. The observation on effect of therapy
      was encouraging and showed less recurrence.

PMID- 22131764
TI  - Clinical efficacy of Panchamuladi Kaala Basti (enema) in the management of
      Amavata (Rheumatoid Arthritis).
AB  - Amavata (Rheumatoid Arthritis) has been a challenging problem to the medical
      field. Various treatment protocols are applied in this disease with partial
      success. In present clinical study, 12 patients of clinically proven Amavata
      (Rheumatoid Arthritis) were treated with Panchamuladi Kaala Basti to evaluate its
      efficacy. All clinical Ayurvediya nidanadi parameters and American Rheumatism
      Association guidelines for Rheumatoid Arthritis were followed. Before treatment
      and after treatment, analysis was done and results were calculated statistically
      using paired 't' test. Results obtained are encouraging and indicate the efficacy
      of Panchamuladi Kaala Basti over Amavata (Rheumatoid arthritis), exploring many
      aspects of this clinical entity.

PMID- 22131765
TI  - Clinical study of Manjishthadi Ghrita in vrana ropana.
AB  - Healing of vrana (wound) is either primary or secondary by nature. Secondary
      healing requires more attention than primary healing. Basically, two things,
      shodhana (making free from undesirable healing factors) and ropana (closure of
      wound), are desirable for proper healing. Many drugs have been described in
      classics for healing, but none of them is capable of healing the wound
      individually. Hence, to fulfill the aim, manjishthadi ghrita was prepared with
      the help of 7 drugs having vrana ropana effects and was evaluated clinically for
      its healing properties in this study. It was used topically in postoperative
      wounds, mostly of ano-rectal cases, twice a day, for 21 days. The follow-up
      period was 1 month to observe the healing as well as vaikritapaham (reduced
      deformity) properties and any untoward effects of the drug. A randomized control
      clinical trial was done. Out of 45 patients, 24 patients in group A were treated
      with "Manjishthadi Ghrita" (treated group), while 21 patients in group B
      (standard group) treated with povidine iodine ointment. Better result was
      observed in the treated group in comparison to the standard group. No adverse
      effect was observed in any patient. Manjishthadi ghrita can be prescribed as a
      local healing agent for common wound.

PMID- 22131766
TI  - A review on management of warts in Ayurveda.
AB  - Human papilloma virus (HPV) is one of the common causes for the warts and most
      people will experience with this infection at some point in their life. In
      Ayurveda, warts can be compared with Charmakeela. The diagnosis is based on
      clinical examination and usually straight forward by visual inspection. The
      treatment of warts has to be done with endurance and careful selection of
      procedure according to the type and site of the disease; otherwise, it may lead
      to cosmetic derangement or recurrence of the ailment. Indications for treatment
      include pain, interference with function, cosmetic embarrassment, and risk of
      malignancy. Regarding the management of this disease, different types of
      treatment procedures are explained in contemporary science. In Ayurveda also,
      various treatment principles explained like administration of drugs internally,
      external application of drugs and parasurgical procedures [i.e. Raktamokshana
      (blood letting), Ksharakarma (chemical cauterization) and Agnikarma (thermal
      cauterization)]. These indigenous treatment methods are minimal invasive
      procedures which do not cause the scar formation, no recurrence and found to be
      more beneficial in the treatment of warts.

PMID- 22131767
TI  - A comparative review study of Sneha Kalpana (Paka) vis-a-vis liposome.
AB  - Ayurvedic dosage forms are very exclusive in its pharmaceutics and therapeutics.
      Sneha Kalpana is a group of products of medicated taila and ghee, these drugs are
      treating very wide range of diseases among patients of all age groups. Liposomal
      system of drug delivery is a new invention in conventional system of medicine.
      This system is also covering a high degree of objective of therapeutics at
      different targets successfully. Probably, here is very distinctive similarity
      between these two on account of their aqueous and oleaginous origin. Most likely,
      these are two faces of same coin. A brief survey of literature is done here to
      explore possibilities of further investigation in benefit of mankind by applying
      wisdom of both fields together. In fact, this is a review paper based on certain
      hypothesis which may be established or rejected factually by further researches.

PMID- 22131768
TI  - Standard manufacturing process of Makaradhwaja prepared by Swarna Patra - Varkha
      and Bhasma.
AB  - Makaradhwaja is an important Kupipakwa Rasayana. It is prepared by using Swarna
      (gold), Parada (mercury) and Gandhaka (sulfur) in different ratios, i.e. 1:8:16,
      1:8:24 and 1:2:4, respectively. The amount of Gandhaka in the Jarana process is
      directly proportional to the increase in therapeutic efficacy and reduces the
      toxicity of the product. Specific temperature pattern for the preparation of
      Makaradhwaja has been followed. In the present study Swarna, Parada and Gandhaka
      were taken in the ratio 1:8:24, respectively, and 12 h of heating for a specified
      amount of Kajjali (i.e., 400 g) in a Kacha Kupi 1/3(rd) of its capacity. There
      are some controversies regarding the form of Swarna (i.e., Swarna Patra Swarna
      Varkha or Swarna Bhasma) used in the preparation of Makaradhwaja. Therefore, in
      the present study, the samples of Makaradhwaja were prepared by Swarna Patra,
      Varkha and Bhasma in different batches. It was found that the use of Varkha
      produced a good-quality product along with the maximum amount of gold, i.e. 268
      ppm, in comparison with Patra, i.e. 131 ppm, and Bhasma, i.e. 19 ppm,
      respectively.

PMID- 22131769
TI  - Pharmacognostic study of Lepidium sativum Linn (Chandrashura).
AB  - Pharmacognosy is the study of naturally occurring biological substances,
      principally those derived from plants that find use in medicine. The word
      "Pharmacognosy" is derived from the Greek "Pharmacon," "a drug" and "gignosco,"
      to acquire knowledge of. It is closely related to both botany and plant chemistry
      and both originated from the earlier scientific studies on medicinal plant. The
      plant kingdom still holds many species of plants containing substances of
      medicinal value which have yet to be discovered large number of plants constantly
      being screened for their possible pharmacological value. The plant Chandrashura
      is being used for the treatment of Amavata, Sandhivata, and Katishula
      successfully. Here, an attempt is made to study the plant pharmacognostically;
      the part taken for study is the seed. Diagnostic features of seed and seed powder
      were also worked out and the details were presented.

PMID- 22131770
TI  - Chronic toxicity study of Butea monosperma (Linn.) Kuntze seeds in albino rats.
AB  - In the present study, toxic effects of powder of seeds of Butea monosperma
      (Linn.) Kuntze were evaluated for a period of 3 months in albino rats. Control
      group received distilled water. The powder suspension was orally given to the
      treated group at a dose of 800 mg/kg/day for 90 days. Parameters like body
      weight, weight of important organs, biochemical, hematological parameters, bone
      marrow cytology and histopathology of vital organs were studied. Test drug
      administration did not affect the body weight, organ weight and bone marrow
      cytology to a significant extent. Among the 18 hematological parameters studied,
      significant changes were observed in three parameters, namely, significant
      decrease in hemoglobin content, red blood cell count and hematocrit. Of 16
      biochemical parameters studied, significant changes were observed in 5
      parameters, namely, decrease in total protein, albumin, bilirubin and significant
      increase in very low density lipoprotein and triglyceride. The histopathology of
      18 organs revealed changes such as fatty changes, glomerular congestion and
      tubular hemorrhage in the kidneys, decrease in the cellularity of the spleen,
      epithelial disruption in jejunum, decrease in spermatogenesis in the testis,
      epithelial proliferation in ventral prostate and decrease in epithelial
      proliferation in the uterus. Thus, toxicity profile obtained from the present
      study shows that B. monosperma seeds are likely to produce toxic effect when
      administered in a powder form.

PMID- 22131771
TI  - Description of Seasonal regimen in Atreya Virachita Sara sangraha.
AB  - In Atreya Virachita Sara sangraha written by Atreya 6 Datta (seasons) Viz.
      Hemanta, Shishira (winter), Vasanta (spring), Grishma (Summer), Varsha (Rainy)
      and Sharada (Autumn) were described in a realistic way. Along with this, there is
      elutriations of specific Roga-Doshas which occur in a particular season and their
      treatment for maintenance of health along with this pathya-apathya (wholesome
      diet-behaviour) and vyayama is indicated. Emphasizing the Ritucharya, greater
      importance is given to Ahara and vihara according to particular Ritu, time of
      vitiation of Doshas as per season & time of pacification of Doshas are also
      described. Along with this importance daily regimen for a particular season is
      also described.

PMID- 22131772
TI  - Cyclosporine 0.05% ophthalmic emulsion for dry eye in Korea: a prospective,
      multicenter, open-label, surveillance study.
AB  - PURPOSE: To assess the effectiveness and tolerability of cyclosporine ophthalmic
      emulsion (CsA) 0.05% in patients with moderate to severe dry eye disease in
      Korea. METHODS: This was a prospective, multicenter, open-label, surveillance
      study of 392 Korean patients with moderate to severe dry eye disease who were
      treated with CsA 0.05% for three months. An assessment of effectiveness was
      performed at baseline, and after 1, 2, and 3 months. The primary effectiveness
      outcomes were changes in ocular symptoms and Schirmer score. The secondary
      effectiveness outcomes were a change in conjunctival staining, use of artificial
      tears, global evaluation of treatment, and patient satisfaction. The primary
      safety outcome was the incidence and nature of adverse events. RESULTS: A total
      of 362 patients completed the study. After three months, all ocular symptom
      scores were significantly reduced compared to the baseline values, while the
      Schirmer scores were significantly increased relative to baseline (p < 0.0001).
      After three months, there were significant reductions from baseline in
      conjunctival staining (p < 0.01) and use of artificial tears (p < 0.0001).
      According to clinicians' global evaluations, most patients (>50%) experienced at
      least a 25% to 50% improvement in symptoms from baseline at each follow-up visit.
      The majority of patients (72.0%) were satisfied with the treatment results, and
      57.2% reported having no or mild symptoms after treatment. The most common
      adverse events were ocular pain (11.0%). CONCLUSIONS: Our findings indicate that
      CsA 0.05% is an effective and tolerable treatment for dry eye disease in Korean
      clinical practice.

PMID- 22131773
TI  - Accuracy of intraocular lens power calculation formulas in primary angle closure
      glaucoma.
AB  - PURPOSE: To compare the accuracy of intraocular lens (IOL) power calculation
      formulas in eyes with primary angle closure glaucoma (ACG). METHODS: This
      retrospective study compared the refractive outcomes of 63 eyes with primary ACG
      with the results of 93 eyes with normal open angles undergoing uneventful
      cataract surgery. Anterior segment biometry including anterior chamber depth,
      axial length, and anterior chamber depth to axial length ratio were compared by
      the IOL Master. Third generation formulas (Hoffer Q and SRK/T) and a fourth
      generation formula (Haigis) were used to predict IOL powers in both groups. The
      predictive accuracy of the formulas was analyzed by comparison of the mean error
      and the mean absolute error (MAE). RESULTS: In ACG patients, anterior chamber
      depth and the anterior chamber depth to axial length ratio were smaller than
      normal controls (all p < 0.05). The MAEs from the ACG group were larger than that
      from the control group in the Haigis formula. The mean absolute error from the
      Haigis formula was the largest and the mean absolute error from the Hoffer Q
      formula was the smallest. CONCLUSIONS: IOL power prediction may be inaccurate in
      ACG patients. The Haigis formula produced more inaccurate results in ACG
      patients, and it is more appropriate to use the Hoffer Q formula to predict IOL
      powers in eyes with primary ACG.

PMID- 22131774
TI  - Photoreceptor disruption related to persistent submacular fluid after successful
      scleral buckle surgery.
AB  - PURPOSE: To investigate serial changes in photoreceptor status and associated
      visual outcome in patients with persistent submacular fluid after successful
      scleral buckle surgery for macula-off rhegmatogenous retinal detachment. METHODS:
      This was a prospective observational case series including 76 consecutive
      patients who underwent successful scleral buckle surgery for macula-off
      rhegmatogenous retinal detachment with symptom duration <=90 days at a single
      tertiary hospital. Optical coherence tomography (OCT) and visual acuity
      examination were performed at one month and three months postoperatively and at
      three-month intervals until the submacular fluid disappeared. Main outcome
      measures were postoperative photoreceptor status on OCT and visual acuity.
      RESULTS: Forty-two patients (55.3%) showed persistent submacular fluid at
      postoperative one month. Of 42 patients with persistent submacular fluid, three
      (7.1%) showed photoreceptor disruption on OCT. None of the 34 patients without
      persistent submacular fluid showed photoreceptor disruption. Two patients (4.8%)
      had progressive photoreceptor disruption, and one patient (2.4%) had early
      photoreceptor disruption. All three patients showed photoreceptor reappearance
      and limited visual restoration after absorption of submacular fluid. Final visual
      acuities were significantly worse in these three patients (20 / 1000, 20 / 133,
      and 20 / 133) compared to those of the other patients (mean, 20 / 30) with
      persistent submacular fluid and intact photoreceptors. CONCLUSIONS: Even after
      successful scleral buckle surgery for rhegmatogenous retinal detachment,
      photoreceptor disruption can occur related to persistent submacular fluid and may
      be a cause of poor visual outcome.

PMID- 22131775
TI  - The clinical outcomes of proton beam radiation therapy for retinoblastomas that
      were resistant to chemotherapy and focal treatment.
AB  - PURPOSE: To evaluate the clinical results of proton beam radiation therapy (PBRT)
      for treatment of retinoblastoma. METHODS: Children with retinoblastoma who were
      treated with chemotherapy and focal treatment such as brachytherapy and
      thermotherapy but showed no response or developed recurrences later received
      PBRT. The PBRT strategy was designed to concentrate the radiation energy to the
      retinoblastoma and spare the surrounding healthy tissue or organs. RESULTS: There
      were three patients who received PBRT. The first patient received PBRT because of
      an initial lack of tumor regression with chemotherapy and brachytherapy. This
      patient showed regression after PBRT. The second patient who developed recurrence
      of retinoblastoma as diffuse infiltrating subretinal seeding was taken PBRT.
      After complete regression, there was recurrence of tumor and the eye was
      enucleated. The third patient had unilateral extensively advanced retinoblastoma.
      Initial chemotherapy failed and tumor recurred. The tumor responded to PBRT and
      regressed significantly. However, the eye developed sudden multiple recurrences,
      so we had to perform enucleation. CONCLUSIONS: PBRT for retinoblastoma was
      effective in cases of showing no response to other treatment modalities. However,
      it should be carefully applied when there was recurrence of diffuse infiltrating
      subretinal seeding or extensively advanced retinoblastoma initially.

PMID- 22131776
TI  - Surgical outcomes for primary rhegmatogenous retinal detachments in patients with
      pseudophakia after phacoemulsification.
AB  - PURPOSE: To evaluate the clinical features and surgical outcomes for primary
      rhegmatogenous retinal detachments (RDs) in patients with pseudophakia after
      phacoemulsification. METHODS: The medical records of patients with pseudophakia
      after phacoemulsification and intraocular lens implantation who had undergone
      surgery for primary rhegmatogenous RDs with a minimum duration of follow-up of 12
      months were reviewed retrospectively. RESULTS: A total of 104 patients were
      enrolled in this study and 106 eyes were analyzed. Post-operative retinal
      attachment was achieved in 87 of the eyes (82.1%) and the final visual acuities
      (logarithm of the minimum angle of resolution) were improved to 0.65 +/- 0.49
      from the baseline measurement of 1.51 +/- 1.14 (p < 0.001). Re-operations were
      performed in 24 of the eyes (22.6%) and there were no visible retinal breaks in
      30 of the eyes (28.3%). The failure to identify a retinal break during surgery
      was associated with a lower rate of retinal reattachment, worse final visual
      acuity, and a higher rate of re-operation (p = 0.002, p = 0.02, and p = 0.002,
      respectively). The location of the identified retinal break was more common in
      the superotemporal quadrant than in the other quadrants. CONCLUSIONS: The
      inability to identify a retinal break during surgery was associated with a poor
      final outcome. Other factors were less important for the functional and anatomic
      success in patients with pseudophakic RDs.

PMID- 22131777
TI  - Comparison of the outcome of repeat trabeculectomy with adjunctive mitomycin C
      and initial trabeculectomy.
AB  - PURPOSE: To compare the efficacy and safety of repeat and initial trabeculectomy
      with mitomycine C (MMC). METHODS: Eighty seven patients, who had underwent repeat
      (repeat group) or initial (initial group) trabeculectomy with MMC, were enrolled
      in this prospective trial. Postoperative outcome measures included the amount of
      decrease in intraocular pressure (IOP), the number of anti-glaucoma medications,
      and the complications. The success of trabeculectomy was defined on the basis of
      three definitions which were: IOP <=18 mmHg (definition 1), IOP <=21 mmHg
      (definition 2), and the amount of decrease in IOP from baseline >=30% (definition
      3). Success was further defined as "complete" when these criteria were obtained
      without any anti-glaucoma medications and "qualified" with or without medical
      therapy and no further surgical procedures. RESULTS: Fifty nine eyes underwent
      initial and 28 eyes underwent repeat trabeculectomy. The mean follow-up period
      was 19.1 +/- 5.9 months. Complete success rates were significantly greater in the
      initial trabeculectomy group (p = 0.02 for definition 1, p = 0.038 for definition
      2, p = 0.003 for definition 3). A higher proportion of eyes in the initial group
      achieved qualified success relative to the group A eyes, but the differences were
      not statistically significant (p = 0.33 for definition 1, p = 0.99 for definition
      2, p = 0.24 for definition 3). The mean number of antiglaucomatous medications at
      the last examination was 1.2 +/- 1.2 in repeat group and 0.7 +/- 1.1 in initial
      group (p = 0.01). The number of complications during the follow up period did not
      differ significantly between the two groups (p = 0.65). CONCLUSIONS: Repeat
      trabeculectomy with MMC has high success and low complication rates in patients
      with previously failed trabeculectomy in spite of the need of higher number of
      anti-glaucoma medications.

PMID- 22131778
TI  - A study of eccentric viewing training for low vision rehabilitation.
AB  - PURPOSE: The definition of eccentric viewing (EV) is using non-foveal preferred
      retinal loci (PRL) for viewing. The purpose of the present study was to
      investigate the clinical effect of EV training for low vision rehabilitation in
      patients with central scotomas. METHODS: The direction of EV was monitored in 30
      low vision patients with central scotomas by moving the patient's view. The PRL
      was found by using a direct ophthalmoscope and retinal camera; the preserved
      visual field was identified using a kinetic visual field analyzer. The
      relationships between EV, PRL, and visual field were evaluated. The patients and
      their guardians were educated regarding EV. After 2 weeks of self-training,
      maintenance of EV was checked and changes in best-corrected visual acuity (BCVA),
      reading speed, and satisfaction questionnaire were evaluated. RESULTS: A
      relationship between EV, PRL, and visual field was in accordance in half of the
      patients. There were no significant differences in demographics and basic visual
      characteristics in patients where the relationship was not in accordance. EV was
      maintained in two-thirds of the patients, but there were no significant
      differences in demographics and basic visual characteristics in patients who
      discontinued EV. There were no significant improvements in BCVA; however, reading
      speed and the satisfaction scores increased significantly with EV. CONCLUSIONS:
      The direction of EV was effectively detected by convenient access using an
      inexpensive method. Functional vision and satisfaction significantly improved
      following EV training. EV training can be used as an effective method for low
      vision rehabilitation in patients with central scotomas.

PMID- 22131779
TI  - Attempts to reduce the progression of myopia and spectacle prescriptions during
      childhood: a survey of eye specialists.
AB  - PURPOSE: To determine methods tried in clinical trials to reduce the progression
      of myopia in children, and spectacle prescribing patterns of hospital
      ophthalmologists. METHODS: A multi-sectioned survey composed of Likert items
      relating to the methods of reducing myopia progression (orthokeratology lenses [O
      K lenses], undercorrected glasses, and topical atropine) and the patterns of
      prescribing spectacles for children (including two cases involving a 5-year-old
      girl and an 8-year-old boy) were distributed to members of the Korean
      Ophthalmological Society, and the collected data was statistically analyzed.
      RESULTS: A total of 78 out of 130 ophthalmologists returned the survey. On a
      scale of 1 to 5, the mean rates of whether the ophthalmologists think O-K lenses
      arrest myopia progression, and whether they recommend their patients to wear O-K
      lenses if indicative, were 3.06 and 2.75, respectively. Moreover, the mean rates
      of whether they consider that wearing glasses which are undercorrected would slow
      down the progression of the myopia, or if they think topical atropine helps in
      arresting myopia progression in children, were 2.34 and 1.27, respectively. In
      response to the case studies, the majority of practitioners preferred to
      prescribe the full amount found in cycloplegic refraction to pediatric patients
      with myopia. CONCLUSIONS: Ophthalmologists in clinical practice encouraged
      children to wear O-K lenses more than undercorrected glasses as a way to retard
      myopia progression. However, the application of atropine is rarely tried in
      clinical trials. In managing pediatric patients with myopia (case specific), the
      majority of the practitioners chose to prescribe glasses with full cycloplegic
      correction.

PMID- 22131781
TI  - c-Fos immunoreactivity in the neurons of the lateral geniculate nucleus in albino
      rats by light exposure after dark rearing.
AB  - PURPOSE: To investigate the effect of dark rearing immediately after birth on the
      maturation of the visual relay neurons in the lateral geniculate nucleus.
      METHODS: Fifty neonatal rats were used. Neonates of the control groups were
      raised under a normal light/dark cycle. Neonates of the experiment groups were
      dark reared and isolated from light during the entire experimental period, then
      exposed to the sun light for 1 hour before sacrifice. RESULTS: In the control
      groups, the neurons in the dorsal lateral geniculate nucleus developed normally
      at each age tested. In the experiment groups, the cytoplasm of the large neurons
      in the dorsal lateral geniculate nucleus of 2-week-old rats contained small
      vesicles, and the cytoplasm of the large neurons of 4-week-old rats was converted
      into a vacuole-like space. Moreover, c-Fos immunoreactivity of the large neurons
      in the dorsal lateral geniculate nucleus in the experiment groups was
      significantly increased compared to that of the control groups. CONCLUSIONS: We
      suppose that the maturation of the neurons in the lateral geniculate nucleus
      might be influenced by light stimulation during the critical period. Furthermore,
      c-Fos could be a marker of the functional activity of the visual relay neurons of
      the lateral geniculate nucleus in albino rats.

PMID- 22131780
TI  - Prevalence of eye diseases in South Korea: data from the Korea National Health
      and Nutrition Examination Survey 2008-2009.
AB  - PURPOSE: The aim of this study is to report on preliminary data regarding the
      prevalence of major eye diseases in Korea. METHODS: We obtained data from the
      Korea National Health and Nutrition Examination Survey, a nation-wide cross
      sectional survey and examinations of the non-institutionalized civilian
      population in South Korea (n = 14,606), conducted from July 2008 to December
      2009. Field survey teams included an ophthalmologist, nurses, and interviewers,
      traveled with a mobile examination unit and performed interviews and
      ophthalmologic examinations. RESULTS: The prevalence of visual impairment,
      myopia, hyperopia and astigmatism in participants over 5 years of age was 0.4 +/-
      0.1%, 53.7 +/- 0.6%, 10.7 +/- 0.4%, and 58.0 +/- 0.6%, respectively. The
      prevalence of strabismus and blepharoptosis in participants over 3 years of age
      was 1.5 +/- 0.1% and 11.0 +/- 0.8%, respectively. In participants over 40 years
      of age, the prevalence of cataract, pterygium, early and late age-related macular
      degeneration, diabetic retinopathy and glaucoma was 40.2 +/- 1.3%, 8.9 +/- 0.5%,
      5.1 +/- 0.3%, 0.5 +/- 0.1%, 13.4 +/- 1.5%, and 2.1 +/- 0.2%, respectively.
      CONCLUSIONS: This is the first nation-wide epidemiologic study conducted in South
      Korea for assessment of the prevalence of eye diseases by both the Korean
      Ophthalmologic Society and the Korea Center for Disease Control and Prevention.
      This study will provide preliminary information for use in further investigation,
      prevention, and management of eye diseases in Korea.

PMID- 22131782
TI  - Calcinosis cutis at the tarsus of the upper eyelid.
AB  - Calcinosis cutis involves the inappropriate deposition of calcium within the
      dermis layer of the skin, and is often associated with rheumatoid disease. A 42
      year-old woman presented for evaluation of a hard palpable mass on the left upper
      eyelid. After everting the eyelid, a large papillomatous mass with a broad base
      was identified on the superior area of the tarsus. The lesion was partially
      excised posteriorly under local anesthesia, and pathologists identified the mass
      as calcinosis cutis. The patient had no systemic or trauma history, and the serum
      levels of calcium and phosphorous were normal. Idiopathic calcinosis cutis should
      be included in the differential diagnosis for a protruding papillomatous mass of
      the tarsal plate, and surgical debulking could be a viable option for large
      protruding lesions, although more follow-up is necessary to monitor regrowth.

PMID- 22131783
TI  - Development of EKC after eximer laser photorefractive surgery and subsequent
      recurrence of EKC-like keratitis.
AB  - This research focuses on four cases of patients having undergone eximer laser
      photorefractive surgery who were diagnosed with adenoviral keratoconjunctivitis
      during the postoperative period and who later developed epidemic
      keratoconjunctivitis (EKC)-like keratitis. Two of the patients had undergone
      laser-assisted subepithelial keratectomy (LASEK), one had undergone laser in situ
      keratomileusis and one had photorefractive keratectomy. After the surgery
      adenoviral keratoconjunctivitis and recurrent late-developing EKC-like keratitis
      were observed in the patients. Recurrent late-developing EKC-like keratitis
      occurred in one of the patients, who had received LASEK as many as three times.
      The others had only one or two episodes.The corneal infiltrates of keratitis
      mainly occurred in the central cornea. Successful resolution of recurrent late
      developing EKC-like keratitis was achieved through the use of topical steroids
      without sequelae and the final best-corrected visual acuity was as good as the
      base line. These keratitis infiltrates have been presumed to represent an immune
      response to the suspected adenoviral antigens deposited in corneal stroma during
      the primary adenoviral infection. Previous reports argued that patients with a
      history of adenoviral ketatoconjunctivitis were succeptible to adenoviral
      keratoconjunctivitis becoming reactivated; however, in our research, our patients
      had their first adenoviral infections after the eximer laser photorefractive
      surgery and reactivation was confirmed. We recommend that attention be paid to
      adenoviral infection after laser refractive operations, because these patients
      seem to have more frequent recurrences.

PMID- 22131784
TI  - Superimposed fungal ulcer after fibrin glue sealant in infectious corneal ulcer.
AB  - A healthy 27-year-old woman with a corneal ulcer underwent fibrin gluing with a
      bandage contact lens twice, due to an impending perforation. The ulcer lesion
      slowly progressed, unresponsive to topical antibiotics and amphotericin B. We
      removed the gluing patch and performed a corneal or scraping or biopsy with
      multiple amniotic membrane grafts to seal the thinned or perforated cornea. Three
      days after the surgery, the corneal cultures grew Fusarium, as well as
      Enterococcus faecalis. Three weeks after surgery, the outermost layer of amniotic
      membranes, serving as a temporary patch, was removed. The anterior chamber was
      clear without cells. The signs of infection clinically and symptomatically
      cleared up four weeks later. Two months after surgery, the lesion became enhanced
      by amniotic membranes. The use of fibrin glue in infectious keratitis should be
      avoided, because it not only masks the underlying lesion, but it also interferes
      with drug penetration into the underlying lesion.

PMID- 22131785
TI  - Presumed necrotizing viral retinitis after intravitreal triamcinolone injection:
      case report.
AB  - A 56-year-old man presented with anterior chamber inflammation, increased
      intraocular pressure, peripheral retinal infiltration, and generalized retinal
      arterial obstruction suggesting acute retinal necrosis five months after
      intravitreal triamcinolone acetonide injection (IVTA). He was treated with
      intravenous antiviral agents and aspirin. Shortly after treatment, retinal
      infiltrations were resolved, and partial recanalization of the obstructed vessel
      was observed. Viral retinitis may occur as an opportunistic infection following
      IVTA due to the local immune modulatory effect of the steroid; hence, close
      observation following IVTA is necessary.

PMID- 22131786
TI  - Optic disc pit with peripapillary retinoschisis presenting as a localized retinal
      nerve fiber layer defect.
AB  - A 59-year-old woman was referred to our clinic for a glaucoma evaluation. The
      visual acuity and intraocular pressure were normal in both eyes. However, red
      free fundus photography in the left eye showed a superotemporal wedge-shaped
      retinal nerve fiber layer defect, and visual field testing showed a corresponding
      partial arcuate scotoma. In an optical coherence tomography examination, the
      macula was flat, but an arcuate-shaped peripapillary retinoschisis was found.
      Further, the retinoschisis seemed to be connected with a superotemporal optic pit
      shown in a disc photograph. After 3 months of a topical prostaglandin analogue
      medication, the intraocular pressure in the retinoschisis eye was lowered from 14
      to 10 mmHg and the peripapillary retinoschisis was almost resolved. We report a
      rare case of an optic disc pit with peripapillary retinoschisis presenting as a
      localized retinal nerve fiber layer defect.

PMID- 22131787
TI  - Horner's syndrome with abducens nerve palsy.
AB  - A 68-year-old male patient presented with a week of sudden diplopia. He had been
      diagnosed with nasopharyngeal cancer 8 months prior and had undergone
      chemotherapy with radiotherapy. Eight-prism diopter right esotropia in the
      primary position and a remarkable limitation in abduction in his right eye were
      observed. Other pupillary disorders and lid drooping were not found. After three
      weeks, the marginal reflex distance 1 was 3 mm in the right eye and 5 mm in the
      left eye. The pupil diameter was 2.5 mm in the right eye, and 3 mm in the left
      eye under room illumination. Under darkened conditions, the pupil diameter was
      3.5 mm in the right eye, and 5 mm in the left eye. After topical application of
      0.5% apraclonidine, improvement in the right ptosis and reversal pupillary
      dilatation were observed. On brain magnetic resonance imaging, enhanced lesions
      on the right cavernous sinus, both sphenoidal sinuses, and skull base suggested
      the invasion of nasopharyngeal cancer. Lesions on the cavernous sinus need to be
      considered in cases of abducens nerve palsy and ipsilateral Horner's syndrome.

PMID- 22131789
TI  - Journal of Manual & Manipulative Therapy announces John Medeiros Award winner.

PMID- 22131788
TI  - A case of optic nerve atrophy with severe disc cupping after methanol poisoning.

PMID- 22131790
TI  - Clustered clinical findings for diagnosis of cervical spine myelopathy.
AB  - Cervical spine myelopathy (CSM) is a clinical diagnosis made with imaging
      confirmation. At present, most clinical tests used to identify CSM are specific
      and no clusters of tests have proven more beneficial than stand alone tests in
      guiding treatment decision making. This study endeavored to produce a cluster of
      predictive clinical findings for a sample of patients using a clinical
      diagnosis/imaging confirmation as the reference standard for cervical spine
      myelopathy. Data from 249 patients with various conditions associated with
      cervical spine dysfunction were analyzed to determine which clinical tests and
      measures, when clustered together, were most diagnostic for CSM. Using
      multivariate regression analyses and calculations for sensitivity, specificity,
      and positive and negative likelihood ratios, a definitive cluster was identified.
      Thirteen clinical findings were investigated for capacity to diagnosis CSM. Five
      clinical: (1) gait deviation; (2) +Hoffmann's test; (3) inverted supinator sign;
      (4) +Babinski test; and (5) age >45 years, were demonstrated the capacity when
      clustered into one of five positive tests to rule out CSM (negative likelihood
      ratio = 0.18; 95% CI = 0.12-0.42), and when clustered into three of five positive
      findings to rule in CSM (positive likelihood ratio = 30.9; 95% CI = 5.5-181.8).
      This study found clustered combinations of clinical findings that could rule in
      and rule out CSM. These clusters may be useful in identifying patients with this
      complex diagnosis in similar patient populations.

PMID- 22131791
TI  - Immediate effects of a thoracic spine thrust manipulation on the autonomic
      nervous system: a randomized clinical trial.
AB  - Thoracic spine manipulation has been shown to be effective for the management of
      neck pain. The purpose of this study was to investigate the immediate effect of a
      T3-T4 spinal thrust manipulation on autonomic nervous system activity in subjects
      with chronic cervical pain. An additional aim was to determine if the
      manipulation resulted in an immediate pain relief in patients with chronic neck
      pain when compared to a placebo intervention. One hundred subjects with chronic
      neck pain were randomly assigned to receive either a thoracic thrust manipulation
      or a placebo intervention. The Friedman's test was used to evaluate the change in
      pupil diameter within both groups. The Wilcoxen signed-ranks test was used to
      explore pupil changes over time and to make paired comparisons of the pupil
      change between the groups. The Mann-Whitney U test was used to compare the change
      in pain perception for the chronic cervical pain group subjects receiving either
      the thrust manipulation or the placebo intervention. The results demonstrated
      that manipulation did not result in a change in sympathetic activity.
      Additionally, there was no significant difference in the subject's pain
      perception (P = 0.961) when comparing the effects of the thrust manipulation to
      the placebo intervention within this group of subjects with chronic neck pain.
      The clinical impression of this study is that manipulation of the thoracic spine
      may not be effective in immediately reducing pain in patients with chronic neck
      pain.

PMID- 22131792
TI  - Differential diagnosis of shoulder and cervical pain: a case report.
AB  - Patients are frequently referred to physical therapy with the diagnosis of
      shoulder and arm pain. During examination and evaluation of the patient, the
      physical therapist must consider all potential causes of the patient's symptoms.
      Three questions are used as the conceptual basis for a diagnosis-based clinical
      decision rule in the management of mechanical and non-mechanical musculoskeletal
      pain when addressing the differential diagnosis of a patient's condition. This
      single patient case report describes the use of these three questions in the
      differential diagnosis of shoulder and arm pain. A 44-year-old male was referred
      with a diagnosis of shoulder impingement syndrome. Each of the three questions
      for differential diagnosis was addressed, and clinical tests and examination
      findings were used to differentiate the origin of the patient's symptoms. The
      intervention provided is outlined along with the patient's response to the
      different treatment strategies provided. This case identifies the need for a
      systematic method of differential diagnosis so that patients are appropriately
      managed.

PMID- 22131794
TI  - Disentangling classification systems from their individual categories and the
      category-specific criteria: an essential consideration to evaluate clinical
      utility.

PMID- 22131793
TI  - Prevalence of classification methods for patients with lumbar impairments using
      the McKenzie syndromes, pain pattern, manipulation, and stabilization clinical
      prediction rules.
AB  - OBJECTIVES: Aims were (1) to determine the proportion of patients with lumbar
      impairments who could be classified at intake by McKenzie syndromes (McK) and
      pain pattern classification (PPCs) using Mechanical Diagnosis and Therapy (MDT)
      assessment methods, manipulation, and stabilization clinical prediction rules
      (CPRs) and (2) for each Man CPR or Stab CPR category, determine classification
      prevalence rates using McK and PPC. METHODS: Eight physical therapists practicing
      in eight diverse clinical settings classified patients typically referred to
      rehabilitation by McKenzie syndromes (i.e. derangement, dysfunction, posture, or
      other), pain pattern classification [i.e. centralization (CEN), not
      centralization (Non CEN), and not classified (NC)], Manipulation CPR (positive,
      negative), and stabilization CPR (positive, negative). Prevalence rates with 95%
      confidence intervals (CI) were calculated for each classification category by
      McK, PPC, and manipulation and stabilization CPRs. Prevalence rates (95% CIs) for
      McK and PPC were calculated for each CPR category separately. RESULTS: Data from
      628 adults [mean age: 52+/-17 years, 56% female] were analyzed. Prevalence rates
      were: McK - derangement 67%, dysfunction 5%, posture 0%, other 28%; PPC - CEN
      43%, Non CEN 39%, NC 18%; manipulation CPR - positive 13%; Stab CPR - positive
      7%. For patients positive for manipulation CPR (n = 79), prevalence rates for
      derangement were 89% and CEN 68%. For patients positive for stabilization CPR (n
      = 41), prevalence rates for derangement were 83% and CEN 80%. DISCUSSION: The
      majority of patients classified based on initial clinical presentation by
      manipulation and stabilization CPRs were also classified as derangements whose
      symptoms centralized. Manipulation and stabilization CPRs may not represent a
      mutually exclusive treatment subgroup but may include patients who can be
      initially treated using a different classification method.

PMID- 22131795
TI  - Authors' response.

PMID- 22131796
TI  - Platform presentations - accepted abstracts - AAOMPT 2010.

PMID- 22131797
TI  - Poster presentations - accepted abstracts - AAOMPT 2010.

PMID- 22131799
TI  - Improvement of physicochemical characteristics of monoepoxide linoleic acid ring
      opening for biolubricant base oil.
AB  - For environmental reasons, a new class of environmentally acceptable and
      renewable biolubricant based on vegetable oils is available. In this study,
      oxirane ring opening reaction of monoepoxide linoleic acid (MEOA) was done by
      nucleophilic addition of oleic acid (OA) with using p-toluene sulfonic acid
      (PTSA) as a catalyst for synthesis of 9(12)-hydroxy-10(13)-oleoxy-12(9)
      octadecanoic acid (HYOOA) and the physicochemical properties of the resulted
      HYOOA are reported to be used as biolubricant base oils. Optimum conditions of
      the experiment using D-optimal design to obtain high yield% of HYOOA and lowest
      OOC% were predicted at OA/MEOA ratio of 0.30 : 1 (w/w), PTSA/MEOA ratio of 0.50 :
      1 (w/w), reaction temperature at 110 degrees C, and reaction time at 4.5 h. The
      results showed that an increase in the chain length of the midchain ester
      resulted in the decrease of pour point (PP) -51 degrees C, increase of viscosity
      index (VI) up to 153, and improvement in oxidative stability (OT) to 180.94
      degrees C.

PMID- 22131801
TI  - Contractile strength during variable heart duration is species and preload
      dependent.
AB  - We investigate the effect of beat-to-beat variability on cardiac contractility.
      Cardiac trabeculae were isolated from the right ventricle of rabbits and beagle
      dogs and stimulated to isometrically contract, alternating between fixed steady
      state versus variable interbeat intervals. Trabeculae were stimulated at
      physiologically relevant frequencies for each species (dog 1 and 4 Hz; rabbit 2
      and 4 Hz) intercalating fixed periods with 40% variability. A subset of the
      trabeculae (at 90% of optimal length) was stretched prior to stimulation between
      5 and 13% and stimulated at the same frequencies with a fixed versus 40%
      variation. Fixed rate response at the same base frequency was measured before and
      after each variable period and the average force reported. In canine preparations
      no change in force was observed as a result of the imposed variability in beat-to
      beat duration. In the rabbit, we observed a nonsignificant decrease in force
      between fixed and variable pacing at both 2 and 4 Hz (n = 8) when 40% variability
      was introduced. When a 5% and 13% stretch was applied, the correlation
      coefficient sharply increased, indicating a more prominent impact of the prebeat
      duration on the following cycle with higher preload.

PMID- 22131800
TI  - Schistosome: its benefit and harm in patients suffering from concomitant
      diseases.
AB  - Schistosomiasis is an important tropical disease affecting approximately 200
      million people worldwide. Because of its chronicity and robust immunomodulatory
      activity, the effects of schistosomes on other diseases, such as allergies,
      autoimmunity, and infectious diseases, have been studied extensively in both
      epidemiological and experimental settings. In this paper, we summarize the
      beneficial and harmful effects of schistosomes. The importance of controlling
      schistosomiasis is also discussed.

PMID- 22131802
TI  - Optical biosensors: a revolution towards quantum nanoscale electronics device
      fabrication.
AB  - The dimension of biomolecules is of few nanometers, so the biomolecular devices
      ought to be of that range so a better understanding about the performance of the
      electronic biomolecular devices can be obtained at nanoscale. Development of
      optical biomolecular device is a new move towards revolution of nano
      bioelectronics. Optical biosensor is one of such nano-biomolecular devices that
      has a potential to pave a new dimension of research and device fabrication in the
      field of optical and biomedical fields. This paper is a very small report about
      optical biosensor and its development and importance in various fields.

PMID- 22131798
TI  - Ion transport by pulmonary epithelia.
AB  - The lung surface of air-breathing vertebrates is formed by a continuous
      epithelium that is covered by a fluid layer. In the airways, this epithelium is
      largely pseudostratified consisting of diverse cell types such as ciliated cells,
      goblet cells, and undifferentiated basal cells, whereas the alveolar epithelium
      consists of alveolar type I and alveolar type II cells. Regulation and
      maintenance of the volume and viscosity of the fluid layer covering the
      epithelium is one of the most important functions of the epithelial barrier that
      forms the outer surface area of the lungs. Therefore, the epithelial cells are
      equipped with a wide variety of ion transport proteins, among which Na+, Cl-, and
      K+ channels have been identified to play a role in the regulation of the fluid
      layer. Malfunctions of pulmonary epithelial ion transport processes and, thus,
      impairment of the liquid balance in our lungs is associated with severe diseases,
      such as cystic fibrosis and pulmonary oedema. Due to the important role of
      pulmonary epithelial ion transport processes for proper lung function, the
      present paper summarizes the recent findings about composition, function, and ion
      transport properties of the airway epithelium as well as of the alveolar
      epithelium.

PMID- 22131803
TI  - Unraveling plant responses to bacterial pathogens through proteomics.
AB  - Plant pathogenic bacteria cause diseases in important crops and seriously and
      negatively impact agricultural production. Therefore, an understanding of the
      mechanisms by which plants resist bacterial infection at the stage of the basal
      immune response or mount a successful specific R-dependent defense response is
      crucial since a better understanding of the biochemical and cellular mechanisms
      underlying these interactions will enable molecular and transgenic approaches to
      crops with increased biotic resistance. In recent years, proteomics has been used
      to gain in-depth understanding of many aspects of the host defense against
      pathogens and has allowed monitoring differences in abundance of proteins as well
      as posttranscriptional and posttranslational processes, protein
      activation/inactivation, and turnover. Proteomics also offers a window to study
      protein trafficking and routes of communication between organelles. Here, we
      summarize and discuss current progress in proteomics of the basal and specific
      host defense responses elicited by bacterial pathogens.

PMID- 22131804
TI  - Dynamic changes in sarcoplasmic reticulum structure in ventricular myocytes.
AB  - The fidelity of excitation-contraction (EC) coupling in ventricular myocytes is
      remarkable, with each action potential evoking a [Ca2+](i) transient. The
      prevalent model is that the consistency in EC coupling in ventricular myocytes is
      due to the formation of fixed, tight junctions between the sarcoplasmic reticulum
      (SR) and the sarcolemma where Ca2+ release is activated. Here, we tested the
      hypothesis that the SR is a structurally inert organelle in ventricular myocytes.
      Our data suggest that rather than being static, the SR undergoes frequent dynamic
      structural changes. SR boutons expressing functional ryanodine receptors moved
      throughout the cell, approaching or moving away from the sarcolemma of
      ventricular myocytes. These changes in SR structure occurred in the absence of
      changes in [Ca2+](i) during EC coupling. Microtubules and the molecular motors
      dynein and kinesin 1(Kif5b) were important regulators of SR motility. These
      findings support a model in which the SR is a motile organelle capable of
      molecular motor protein-driven structural changes.

PMID- 22131805
TI  - T cells as vehicles for cancer vaccination.
AB  - The success of cancer vaccines is dependent on the delivery of tumor-associated
      antigens (TAAs) within lymphoid tissue in the context of costimulatory molecules
      and immune stimulatory cytokines. Dendritic cells (DCs) are commonly utilized to
      elicit antitumor immune responses due to their attractive costimulatory molecule
      and cytokine expression profile. However, the efficacy of DC-based vaccines is
      limited by the poor viability and lymph-node migration of exogenously generated
      DCs in vivo. Alternatively, adoptively transferred T cells persist for long
      periods of time in vivo and readily migrate between the lymphoid and vascular
      compartments. In addition, T cells may be genetically modified to express both
      TAA and DC-activating molecules, suggesting that T cells may be ideal candidates
      to serve as cellular vehicles for antigen delivery to lymph node-resident DCs in
      vivo. This paper discusses the concept of using T cells to induce tumor-specific
      immunity for vaccination against cancer.

PMID- 22131806
TI  - Emerging functions of transcription factors in malaria parasite.
AB  - Transcription is a process by which the genetic information stored in DNA is
      converted into mRNA by enzymes known as RNA polymerase. Bacteria use only one RNA
      polymerase to transcribe all of its genes while eukaryotes contain three RNA
      polymerases to transcribe the variety of eukaryotic genes. RNA polymerase also
      requires other factors/proteins to produce the transcript. These factors
      generally termed as transcription factors (TFs) are either associated directly
      with RNA polymerase or add in building the actual transcription apparatus. TFs
      are the most common tools that our cells use to control gene expression.
      Plasmodium falciparum is responsible for causing the most lethal form of malaria
      in humans. It shows most of its characteristics common to eukaryotic
      transcription but it is assumed that mechanisms of transcriptional control in P.
      falciparum somehow differ from those of other eukaryotes. In this article we
      describe the studies on the main TFs such as myb protein, high mobility group
      protein and ApiA2 family proteins from malaria parasite. These studies show that
      these TFs are slowly emerging to have defined roles in the regulation of gene
      expression in the parasite.

PMID- 22131807
TI  - Thin filament-reconstituted skinned muscle fibers for the study of muscle
      physiology.
AB  - We review the use of thin filament-reconstituted muscle fibers in the study of
      muscle physiology. Thin filament extraction and reconstitution protocol is a
      powerful technique to study the role of each component of the thin filament. It
      is also useful for studying the properties of genetically modified molecules such
      as actin and tropomyosin. We also review the combination of this protocol with
      sinusoidal analysis, which will provide a solid technique for determining the
      effect of regulatory proteins on actomyosin interaction and concomitant cross
      bridge kinetics. We suggest that thin filament-reconstituted muscle fibers are an
      ideal system for studying muscle physiology especially when gene modifications of
      actin or tropomyosin are involved.

PMID- 22131808
TI  - Immunodiagnosis of neurocysticercosis: ways to focus on the challenge.
AB  - Neurocysticercosis (NCC) is a disease of the central nervous system that is
      considered a public health problem in endemic areas. The definitive diagnosis of
      this disease is made using a combination of tools that include imaging of the
      brain and immunodiagnostic tests, but the facilities for performing them are
      usually not available in endemic areas. The immunodiagnosis of NCC is a useful
      tool that can provide important information on whether a patient is infected or
      not, but it presents many drawbacks as not all infected patients can be detected.
      These tests rely on purified or semipurified antigens that are sometimes
      difficult to prepare. Recent efforts have focused on the production of
      recombinant or synthetic antigens for the immunodiagnosis of NCC and interesting
      studies propose the use of new elements as nanobodies for diagnostic purposes.
      However, an immunodiagnostic test that can be considered as "gold standard" has
      not been developed so far. The complex nature of cysticercotic disease and the
      simplicity of common immunological assumptions involved explain the low scores
      and reproducibility of immunotests in the diagnosis of NCC. Here, the most
      important efforts for developing an immunodiagnostic test of NCC are listed and
      discussed. A more punctilious strategy based on the design of panels of confirmed
      positive and negative samples, the use of blind tests, and a worldwide effort is
      proposed in order to develop an immunodiagnostic test that can provide comparable
      results. The identification of a set of specific and representative antigens of
      T. solium and a thorough compilation of the many forms of antibody response of
      humans to the many forms of T. solium disease are also stressed as necessary.

PMID- 22131809
TI  - Creep behavior of passive bovine extraocular muscle.
AB  - This paper characterized bovine extraocular muscles (EOMs) using creep, which
      represents long-term stretching induced by a constant force. After preliminary
      optimization of testing conditions, 20 fresh EOM samples were subjected to four
      different loading rates of 1.67, 3.33, 8.33, and 16.67%/s, after which creep was
      observed for 1,500 s. A published quasilinear viscoelastic (QLV) relaxation
      function was transformed to a creep function that was compared with data.
      Repeatable creep was observed for each loading rate and was similar among all six
      anatomical EOMs. The mean creep coefficient after 1,500 seconds for a wide range
      of initial loading rates was at 1.37 +/- 0.03 (standard deviation, SD). The creep
      function derived from the relaxation-based QLV model agreed with observed creep
      to within 2.7% following 16.67%/s ramp loading. Measured creep agrees closely
      with a derived QLV model of EOM relaxation, validating a previous QLV model for
      characterization of EOM biomechanics.

PMID- 22131810
TI  - Colocalization of serum amyloid a with microtubules in human coronary artery
      endothelial cells.
AB  - Serum amyloid A (SAA) acts as a major acute phase protein and represents a
      sensitive and accurate marker of inflammation. Besides its hepatic origin, as the
      main source of serum SAA, this protein is also produced extrahepatically. The
      mRNA levels of SAA become significantly elevated following proinflammatory
      stimuli, as well as, are induced through their own positive feedback in human
      primary coronary artery endothelial cells. However, the intracellular functions
      of SAA are so far unknown. Colocalization of SAA with cytoskeletal filaments has
      previously been proposed, so we analyzed the colocalization of SAA with all three
      cytoskeletal elements: actin filaments, vimentin filaments, and microtubules.
      Immunofluorescent double-labeling analyses confirmed by PLA method revealed a
      strict colocalization of SAA with microtubules and a very infrequent attachment
      to vimentin while the distribution of actin filaments appeared clearly separated
      from SAA staining. Also, no significant colocalization was found between SAA and
      endomembranes labeled with the fluorescent lipid stain DiO6. However, SAA appears
      to be located also unbound in the cytosol, as well as inside the nucleus and
      within nanotubes extending from the cells or bridging neighboring cells. These
      different locations of SAA in endothelial cells strongly indicate multiple
      potential functions of this protein.

PMID- 22131811
TI  - Survival of exfoliated epithelial cells: a delicate balance between anoikis and
      apoptosis.
AB  - The recovery of exfoliated cells from biological fluids is a noninvasive
      technology which is in high demand in the field of translational research.
      Exfoliated epithelial cells can be isolated from several body fluids (i.e.,
      breast milk, urines, and digestives fluids) as a cellular mixture (senescent,
      apoptotic, proliferative, or quiescent cells). The most intriguing are quiescent
      cells which can be used to derive primary cultures indicating that some
      phenotypes retain clonogenic potentials. Such exfoliated cells are believed to
      enter rapidly in anoikis after exfoliation. Anoikis can be considered as an
      autophagic state promoting epithelial cell survival after a timely loss of
      contact with extracellular matrix and cell neighbors. This paper presents current
      understanding of exfoliation along with the influence of methodology on the type
      of gastrointestinal epithelial cells isolated and, finally, speculates on the
      balance between anoikis and apoptosis to explain the survival of gastrointestinal
      epithelial cells in the environment.

PMID- 22131812
TI  - Alpha 1,3-galactosyltransferase deficiency in pigs increases sialyltransferase
      activities that potentially raise non-gal xenoantigenicity.
AB  - We examined whether deficiency of the GGTA1 gene in pigs altered the expression
      of several glycosyltransferase genes. Real-time RT-PCR and glycosyltransferase
      activity showed that 2 sialyltransferases [alpha2,3-sialyltransferase
      (alpha2,3ST) and alpha2,6-sialyltransferase (alpha2,6ST)] in the heterozygote
      GalT KO liver have higher expression levels and activities compared to controls.
      Enzyme-linked lectin assays indicated that there were also more sialic acid
      containing glycoconjugate epitopes in GalT KO livers than in controls. The
      elevated level of sialic-acid-containing glycoconjugate epitopes was due to the
      low level of alpha-Gal in heterozygote GalT KO livers. Furthermore, proteomics
      analysis showed that heterozygote GalT KO pigs had a higher expression of NAD+
      isocitrate dehydrogenase (IDH), which is related to the CMP-N-acetylneuraminic
      acid hydroxylase (CMAH) enzyme reaction. These findings suggest the deficiency of
      GGTA1 gene in pigs results in increased production of N-glycolylneuraminic acid
      (Neu5Gc) due to an increase of alpha2,6-sialyltransferase and a CMAH cofactor,
      NAD+-IDH. This indicates that Neu5Gc may be a critical xenoantigen. The deletion
      of the CMAH gene in the GalT KO background is expected to further prolong
      xenograft survival.

PMID- 22131813
TI  - Cytotoxic effects of native and recombinant frutalin, a plant galactose-binding
      lectin, on HeLa cervical cancer cells.
AB  - Frutalin is the alpha-D-galactose-binding lectin isolated from breadfruit seeds.
      Frutalin was obtained from two different sources: native frutalin was purified
      from its natural origin, and recombinant frutalin was produced and purified from
      Pichia pastoris. This work aimed to study and compare the effect of native and
      recombinant frutalin on HeLa cervical cancer cells proliferation and apoptosis.
      Furthermore, the interaction between frutalin and the HeLa cells was investigated
      by confocal microscopy. Despite having different carbohydrate-binding affinities,
      native and recombinant frutalin showed an identical magnitude of cytotoxicity on
      HeLa cells growth (IC50~100 MUg/mL) and equally induced cell apoptosis. The
      interaction studies showed that both lectins were rapidly internalised and
      targeted to HeLa cell's nucleus. Altogether, these results indicate that frutalin
      action is not dependent on its sugar-binding properties. This study provides
      important information about the bioactivity of frutalin and contributes to the
      understanding of the plant lectins cytotoxic activity.

PMID- 22131814
TI  - Exact and approximate stochastic simulation of intracellular calcium dynamics.
AB  - In simulations of chemical systems, the main task is to find an exact or
      approximate solution of the chemical master equation (CME) that satisfies certain
      constraints with respect to computation time and accuracy. While Brownian motion
      simulations of single molecules are often too time consuming to represent the
      mesoscopic level, the classical Gillespie algorithm is a stochastically exact
      algorithm that provides satisfying results in the representation of calcium
      microdomains. Gillespie's algorithm can be approximated via the tau-leap method
      and the chemical Langevin equation (CLE). Both methods lead to a substantial
      acceleration in computation time and a relatively small decrease in accuracy.
      Elimination of the noise terms leads to the classical, deterministic reaction
      rate equations (RRE). For complex multiscale systems, hybrid simulations are
      increasingly proposed to combine the advantages of stochastic and deterministic
      algorithms. An often used exemplary cell type in this context are striated muscle
      cells (e.g., cardiac and skeletal muscle cells). The properties of these cells
      are well described and they express many common calcium-dependent signaling
      pathways. The purpose of the present paper is to provide an overview of the
      aforementioned simulation approaches and their mutual relationships in the
      spectrum ranging from stochastic to deterministic algorithms.

PMID- 22131815
TI  - Planar cell polarity signaling pathway in congenital heart diseases.
AB  - Congenital heart disease (CHD) is a common cardiac disorder in humans. Despite
      many advances in the understanding of CHD and the identification of many
      associated genes, the fundamental etiology for the majority of cases remains
      unclear. The planar cell polarity (PCP) signaling pathway, responsible for tissue
      polarity in Drosophila and gastrulation movements and cardiogenesis in
      vertebrates, has been shown to play multiple roles during cardiac differentiation
      and development. The disrupted function of PCP signaling is connected to some
      CHDs. Here, we summarize our current understanding of how PCP factors affect the
      pathogenesis of CHD.

PMID- 22131816
TI  - Safety and clinical usage of newcastle disease virus in cancer therapy.
AB  - Newcastle disease virus (NDV) is an avian virus that causes deadly infection to
      over 250 species of birds, including domestic and wild-type, thus resulting in
      substantial losses to the poultry industry worldwide. Many reports have
      demonstrated the oncolytic effect of NDV towards human tumor cells. The
      interesting aspect of NDV is its ability to selectively replicate in cancer
      cells. Some of the studies have undergone human clinical trials, and favorable
      results were obtained. Therefore, NDV strains can be the potential therapeutic
      agent in cancer therapy. However, investigation on the therapeutic perspectives
      of NDV, especially human immunological effects, is still ongoing. This paper
      provides an overview of the current studies on the cytotoxic and anticancer
      effect of NDV via direct oncolysis effects or immune stimulation. Safety of NDV
      strains applied for cancer immunotherapy is also discussed in this paper.

PMID- 22131817
TI  - Proteomics in molecular diagnosis: typing of amyloidosis.
AB  - Amyloidosis is a group of disorders caused by deposition of misfolded proteins as
      aggregates in the extracellular tissues of the body, leading to impairment of
      organ function. Correct identification of the causal amyloid protein is
      absolutely crucial for clinical management in order to avoid misdiagnosis and
      inappropriate, potentially harmful treatment, to assess prognosis and to offer
      genetic counselling if relevant. Current diagnostic methods, including antibody
      based amyloid typing, have limited ability to detect the full range of amyloid
      forming proteins. Recent investigations into proteomic identification of amyloid
      protein have shown promise. This paper will review the current state of the art
      in proteomic analysis of amyloidosis, discuss the suitability of techniques based
      on the properties of amyloidosis, and further suggest potential areas of
      development. Establishment of mass spectrometry aided amyloid typing procedures
      in the pathology laboratory will allow accurate amyloidosis diagnosis in a timely
      manner and greatly facilitate clinical management of the disease.

PMID- 22131818
TI  - Osteopontin alleles are associated with clinical characteristics in systemic
      lupus erythematosus.
AB  - Variants of the osteopontin (OPN) gene have been associated with systemic lupus
      erythematosus (SLE) susceptibility and cytokine profiles in SLE patients. It is
      not known whether these alleles are associated with specific clinical phenotypes
      in SLE. We studied 252 well-characterized SLE patients from a multiethnic cohort,
      genotyping the rs11730582, rs28357094, rs6532040, and rs9138 SNPs in the OPN
      gene. Ancestry informative markers were used to control for genetic ancestry. The
      SLE-risk allele rs9138C in the 3' UTR region was associated with photosensitivity
      in lupus patients across all ancestral backgrounds (meta-analysis OR = 3.2, 95%
      CI = 1.6-6.5, P = 1.0 * 10-3). Additionally, the promoter variant rs11730582C
      demonstrated suggestive evidence for association with two hematologic traits:
      thrombocytopenia (OR = 2.1, P = 0.023) and hemolytic anemia (OR = 2.6, P =
      0.036). These clinical associations with SNPs in the promoter and 3' UTR regions
      align with previously reported SLE-susceptibility SNPs in OPN and suggest
      potential roles for these variants in antibody-mediated cytopenias and skin
      inflammation in SLE.

PMID- 22131819
TI  - Role of positive selection in functional divergence of mammalian neuronal
      apoptosis inhibitor proteins during evolution.
AB  - Neuronal apoptosis inhibitor proteins (NAIPs) are members of Nod-like receptor
      (NLR) protein family. Recent research demostrated that some NAIP genes were
      strongly associated with both innate immunity and many inflammatory diseases in
      humans. However, no similar phenomena have been reported in other mammals.
      Furthermore, some NAIP genes have undergone pseudogenization or have been lost
      during the evolution of some higher mammals. We therefore aimed to determine if
      functional divergence had occurred, and if natural selection had played an
      important role in the evolution of these genes. The results showed that NAIP
      genes have undergone pseudogenization and functional divergence, driven by
      positive selection. Positive selection has also influenced NAIP protein
      structure, resulting in further functional divergence.

PMID- 22131820
TI  - Effects of theophylline on anesthetized malignant hyperthermia-susceptible pigs.
AB  - BACKGROUND: Theophylline was shown to induce contracture development in porcine
      malignant hyperthermia (MH) susceptible (MHS) skeletal muscles in vitro. The
      purpose of the current study was to investigate the in vivo effects of
      theophylline in MHS and MH normal (MHN) swine. METHODS: MH-trigger-free general
      anesthesia was performed in MHS and MHN swine. Theophylline was administered
      intravenously in cumulative doses up to 93.5 mg.kg-1. The clinical occurrence of
      MH was defined by changes of central-venous pCO2, central-venous pH, and body
      core temperature. RESULTS: Theophylline induced comparable clinical alterations
      in the anesthetized MHS and MHN swine, especially in regard to hemodynamic data.
      No pig developed hypermetabolism and/or MH according to defined criteria. All
      animals died with tachycardia followed by ventricular fibrillation. CONCLUSIONS:
      The cumulative theophylline doses used in this study were much higher than doses
      used therapeutically in humans, as demonstrated by measured blood concentrations.
      Theophylline is thus not a trigger of MH in genetically determined swine.

PMID- 22131821
TI  - Cervicovaginal safety of the formulated, biguanide-based human immunodeficiency
      virus type 1 (HIV-1) inhibitor NB325 in a murine model.
AB  - Vaginal microbicides that reduce or eliminate the risk of HIV-1 sexual
      transmission must do so safely without adversely affecting the integrity of the
      cervicovaginal epithelium. The present studies were performed to assess the
      safety of the biguanide-based antiviral compound NB325 in a formulation suitable
      for topical application. Experiments were performed using a mouse model of
      cervicovaginal microbicide application, which was previously shown to be
      predictive of topical agent toxicity revealed in microbicide clinical trials.
      Mice were exposed vaginally to unformulated NB325 or NB325 formulated in the
      hydroxyethyl cellulose "universal placebo." Following exposures to formulated 1%
      NB325 for 10 min to 24 h, the vaginal and cervical epithelia were generally
      intact, although some areas of minimal vaginal epithelial damage were noted.
      Although formulated NB325 appeared generally safe for application in these
      studies, the low but observable level of toxicity suggests the need for
      improvements in the compound and/or formulation.

PMID- 22131822
TI  - Plasma cell cerebrospinal fluid pleocytosis does not predict West Nile virus
      infection.
AB  - PURPOSE: Diagnosis of WNV (WNV) relies upon serologic testing which may take
      several days after the onset of clinical symptoms to turn positive. Anecdotal
      reports suggest the presence of plasma cells or plasmacytoid lymphocytes in the
      cerebrospinal fluid (CSF) may be an early indicator of WNV infection. METHODS:
      The CSFs of 89 patients (12 with WNV, 12 with other viral illness {OVI}, and 65
      with nonviral illness{NVI}) were compared for the presence of either plasma cells
      or plasmacytoid lymphocytes. RESULTS: Plasma cells were rarely seen in any of the
      patients. Plasmacytoid lymphocytes were more commonly seen in WNV (58%) and OVI
      (50%) than NVI (11%). The differences were significant for WNV versus NVI, but
      not WNV versus OVI (P < 0.001 and P = 0.58, resp.). CONCLUSIONS: A CSF
      pleocytosis with plasma cells or plasmacytoid lymphocytes was neither sensitive
      nor specific for the diagnosis of WNV infection.

PMID- 22131824
TI  - The effect of Tinospora crispa on serum glucose and insulin levels in patients
      with type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine the effects of Tinospora crispa on serum glucose and
      insulin levels in healthy subjects and patients with type 2 diabetes mellitus.
      METHOD: Serum from 10 healthy subjects and 10 diabetic participants, who had
      fasted overnight, were obtained every 30-60 minutes during the 3 hours of
      continued fasting and during the 3 hours after ingestion of 75 g of glucose with
      or without ingestion of 125 or 250 g of Tinospora crispa dry powder capsule.
      Glucose and Insulin levels were analyzed and the areas under the curve for mean
      serum glucose and insulin levels were calculated. RESULT: The areas under the
      curve of mean serum glucose and insulin levels in both healthy and diabetic
      participants were not significantly different between with or without Tinospora
      crispa dry powder capsule. In diabetic participants the area under the curve of
      glucose was slightly lesser when 250 mg of Tinospora crispa was ingested, but not
      reaching statistical significance (478 and 444 mg min/ml, resp., P = 0.57).
      CONCLUSION: The results suggest that Tinospora crispa ingestion cannot affect
      serum glucose and insulin levels in healthy subjects or patients with type 2
      diabetes mellitus.

PMID- 22131823
TI  - Applications of the phytomedicine Echinacea purpurea (Purple Coneflower) in
      infectious diseases.
AB  - Extracts of Echinacea purpurea (EP, purple coneflower) have been used
      traditionally in North America for the treatment of various types of infections
      and wounds, and they have become very popular herbal medicines globally. Recent
      studies have revealed that certain standardized preparations contain potent and
      selective antiviral and antimicrobial activities. In addition, they display
      multiple immune-modulatory activities, comprising stimulation of certain immune
      functions such as phagocytic activity of macrophages and suppression of the
      proinflammatory responses of epithelial cells to viruses and bacteria, which are
      manifested as alterations in secretion of various cytokines and chemokines. These
      immune modulations result from upregulation or downregulation of the relevant
      genes and their transcription factors. All these bioactivities can be
      demonstrated at noncytotoxic concentrations of extract and appear to be due to
      multiple components rather than the individual chemical compounds that
      characterize Echinacea extracts. Potential applications of the bioactive extracts
      may go beyond their traditional uses.

PMID- 22131825
TI  - Treatment of oral squamous cell carcinoma using anti-HER2 immunonanoshells.
AB  - BACKGROUND: Worldwide, oral squamous cell carcinoma (potentially mediated by
      HER2) is recognized as the most commonly occurring malignant neoplasm of the oral
      cavity. Anti-HER2 nanobodies conjugated to gold-silica nanoshells and used as
      photothermal treatment for oral squamous cell carcinoma may provide a novel
      therapeutic alternative to current treatment for this disease. METHODS: KB
      epithelial or HeLaS3 cell cultures (controls) were exposed to these
      immunonanoshells, and plasmon resonance electron initiation specific to gold was
      employed to burn the tumor cells. RESULTS: Following this treatment, significant
      cell death occurred in the KB tumor cell cultures while there was no evidence of
      cellular damage or death in the HeLaS3 cell cultures. CONCLUSION: These findings
      suggest that photothermal treatment of oral squamous cell carcinoma has
      considerable advantages.

PMID- 22131826
TI  - The changing face of dentistry: nanotechnology.
AB  - The human body comprises molecules; hence, the availability of molecular
      nanotechnology will permit dramatic progress to address medical problems and will
      use molecular knowledge to maintain and improve human health at the molecular
      scale. Nanomedicine could develop devices that are able to work inside the human
      body in order to identify the early presence of a disease, and to identify and
      quantify toxic molecules and tumor cells, for example. Nanodentistry will make
      possible the maintenance of comprehensive oral health by employing nanomaterials,
      including tissue engineering and, ultimately, dental nanorobots. This review is
      an attempt to highlight the possible applications of nanotechnology and the use
      of nanomaterials in dentistry.

PMID- 22131827
TI  - Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in
      vivo.
AB  - PURPOSE: This research was conducted to assess the biocompatibility of the core
      shell Fe(3)O(4)@ Au composite magnetic nanoparticles (MNPs), which have potential
      application in tumor hyperthermia. METHODS: Fe(3)O(4)@Au composite MNPs with core
      shell structure were synthesized by reduction of Au(3+) in the presence of
      Fe(3)O(4)-MNPs prepared by improved co-precipitation. Cytotoxicity assay,
      hemolysis test, micronucleus (MN) assay, and detection of acute toxicity in mice
      and beagle dogs were then carried out. RESULTS: The result of cytotoxicity assay
      showed that the toxicity grade of this material on mouse fibroblast cell line (L
      929) was classified as grade 1, which belongs to no cytotoxicity. Hemolysis rates
      showed 0.278%, 0.232%, and 0.197%, far less than 5%, after treatment with
      different concentrations of Fe(3)O(4)@Au composite MNPs. In the MN assay, there
      was no significant difference in MN formation rates between the experimental
      groups and negative control (P > 0.05), but there was a significant difference
      between the experimental groups and the positive control (P < 0.05). The median
      lethal dose of the Fe(3)O(4)@Au composite MNPs after intraperitoneal
      administration in mice was 8.39 g/kg, and the 95% confidence interval was 6.58
      10.72 g/kg, suggesting that these nanoparticles have a wide safety margin. Acute
      toxicity testing in beagle dogs also showed no significant difference in body
      weight between the treatment groups at 1, 2, 3, and 4 weeks after liver injection
      and no behavioral changes. Furthermore, blood parameters, autopsy, and
      histopathological studies in the experimental group showed no significant
      difference compared with the control group. CONCLUSION: The results indicate that
      Fe(3)O(4)@Au composite MNPs appear to be highly biocompatible and safe
      nanoparticles that are suitable for further application in tumor hyperthermia.

PMID- 22131828
TI  - Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in
      human endothelial cells: inflammatory and cytotoxic effects.
AB  - BACKGROUND: The purpose of this study was to investigate the mechanism of noxious
      effects of amorphous silica nanoparticles on human endothelial cells. METHODS:
      Nanoparticle uptake was examined by transmission electron microscopy.
      Electrochemical nanosensors were used to measure the nitric oxide (NO) and
      peroxynitrite (ONOO(-)) released by a single cell upon nanoparticle stimulation.
      The downstream inflammatory effects were measured by an enzyme-linked
      immunosorbent assay, real-time quantitative polymerase chain reaction, and flow
      cytometry, and cytotoxicity was measured by lactate dehydrogenase assay. RESULTS:
      We found that the silica nanoparticles penetrated the plasma membrane and rapidly
      stimulated release of cytoprotective NO and, to a greater extent, production of
      cytotoxic ONOO(-). The low [NO]/[ONOO(-)] ratio indicated increased
      nitroxidative/oxidative stress and correlated closely with endothelial
      inflammation and necrosis. This imbalance was associated with nuclear factor
      kappaB activation, upregulation of key inflammatory factors, and cell death.
      These effects were observed in a nanoparticle size-dependent and concentration
      dependent manner. CONCLUSION: The [NO]/[ONOO(-)] imbalance induced by amorphous
      silica nanoparticles indicates a potentially deleterious effect of silica
      nanoparticles on vascular endothelium.

PMID- 22131829
TI  - Effect of poly-alpha, gamma, L-glutamic acid as a capping agent on morphology and
      oxidative stress-dependent toxicity of silver nanoparticles.
AB  - Highly stable dispersions of nanosized silver particles were synthesized using a
      straightforward, cost-effective, and ecofriendly method. Nontoxic glucose was
      utilized as a reducing agent and poly-alpha, gamma, L-glutamic acid (PGA), a
      naturally occurring anionic polymer, was used as a capping agent to protect the
      silver nanoparticles from agglomeration and render them biocompatible. Use of
      ammonia during synthesis was avoided. Our study clearly demonstrates how the
      concentration of the capping agent plays a major role in determining the
      dimensions, morphology, and stability, as well as toxicity of a silver colloidal
      solution. Hence, proper optimization is necessary to develop silver colloids of
      narrow size distribution. The samples were characterized by Fourier transform
      infrared spectroscopy, ultraviolet-visible spectroscopy, field-emission scanning
      electron microscopy, transmission electron microscopy, and zeta potential
      measurement. MTT assay results indicated good biocompatibility of the PGA-capped
      silver nanoparticles. Formation of intracellular reactive oxygen species was
      measured spectrophotometrically using 2,7-dichlorofluorescein diacetate as a
      fluorescent probe, and it was shown that the PGA-capped silver nanoparticles did
      not induce intracellular formation of reactive oxygen species.

PMID- 22131830
TI  - Translocation of PEGylated quantum dots across rat alveolar epithelial cell
      monolayers.
AB  - BACKGROUND: In this study, primary rat alveolar epithelial cell monolayers
      (RAECM) were used to investigate transalveolar epithelial quantum dot trafficking
      rates and underlying transport mechanisms. METHODS: Trafficking rates of quantum
      dots (PEGylated CdSe/ZnS, core size 5.3 nm, hydrodynamic size 25 nm) in the
      apical-to-basolateral direction across RAECM were determined. Changes in
      bioelectric properties (ie, transmonolayer resistance and equivalent active ion
      transport rate) of RAECM in the presence or absence of quantum dots were
      measured. Involvement of endocytic pathways in quantum dot trafficking across
      RAECM was assessed using specific inhibitors (eg, methyl-beta-cyclodextrin,
      chlorpromazine, and dynasore for caveolin-, clathrin-, and dynamin-mediated
      endocytosis, respectively). The effects of lowering tight junctional resistance
      on quantum dot trafficking were determined by depleting Ca(2+) in apical and
      basolateral bathing fluids of RAECM using 2 mM EGTA. Effects of temperature on
      quantum dot trafficking were studied by lowering temperature from 37 degrees C to
      4 degrees C. RESULTS: Apical exposure of RAECM to quantum dots did not elicit
      changes in transmonolayer resistance or ion transport rate for up to 24 hours;
      quantum dot trafficking rates were not surface charge-dependent; methyl-beta
      cyclodextrin, chlorpromazine, and dynasore did not decrease quantum dot
      trafficking rates; lowering of temperature decreased transmonolayer resistance by
      approximately 90% with a concomitant increase in quantum dot trafficking by about
      80%; and 24 hours of treatment of RAECM with EGTA decreased transmonolayer
      resistance by about 95%, with increased quantum dot trafficking of up to
      approximately 130%. CONCLUSION: These data indicate that quantum dots do not
      injure RAECM and that quantum dot trafficking does not appear to take place via
      endocytic pathways involving caveolin, clathrin, or dynamin. We conclude that
      quantum dot translocation across RAECM takes place via both transcellular and
      paracellular pathways and, based on comparison with our prior studies,
      interactions of nanoparticles with RAECM are strongly dependent on nanoparticle
      composition and surface properties.

PMID- 22131831
TI  - Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo
      study.
AB  - In recent years, advances in molecular biology and cancer research have led to
      the identification of sensitive and specific biomarkers that associate with
      various types of cancer. However, in vivo cancer detection methods with computed
      tomography, based on tracing and detection of these molecular cancer markers, are
      unavailable today. This paper demonstrates in vivo the feasibility of cancer
      diagnosis based on molecular markers rather than on anatomical structures, using
      clinical computed tomography. Anti-epidermal growth factor receptor conjugated
      gold nanoparticles (30 nm) were intravenously injected into nude mice implanted
      with human squamous cell carcinoma head and neck cancer. The results clearly
      demonstrate that a small tumor, which is currently undetectable through
      anatomical computed tomography, is enhanced and becomes clearly visible by the
      molecularly-targeted gold nanoparticles. It is further shown that active tumor
      targeting is more efficient and specific than passive targeting. This noninvasive
      and nonionizing molecular cancer imaging tool can facilitate early cancer
      detection and can provide researchers with a new technique to investigate in vivo
      the expression and activity of cancer-related biomarkers and molecular processes.

PMID- 22131832
TI  - Long-circulating delivery of bioactive polysaccharide from radix ophiopogonis by
      PEGylation.
AB  - BACKGROUND: Radix ophiopogonis polysaccharide (ROP) has been found to be
      effective against myocardial ischemia. One of main problems with its use is its
      short in-vivo half-life, which makes the development of an effective delivery
      system necessary. To achieve better therapeutic effects and patient compliance by
      prolonging its retention in plasma and increasing its distribution in targets,
      ROP was PEGylated (PEG, polyethylene glycol) in this study. METHODS: Through a
      moderate coupling reaction between hydroxyl-activated ROP and amino-terminated
      methoxy-PEG (mPEG) (30 or 40 kDa), together with a greater than 1 molar ratio of
      ROP to mPEG in reaction, long-circulating and potentially bioactive PEGylated
      ROPs, with PEG grafting number of ~1.0, were prepared, characterized, and the
      pharmacokinetics evaluated. RESULTS: Relative to ROP, whose half-life was
      approximately 0.7 hours, the two conjugates prepared, following intravenous
      administration, showed markedly prolonged retention in systemic circulation with
      half-lives in blood of 78.4 and 88.3 hours, respectively. When given
      subcutaneously, their in-vivo mean residence times were further markedly
      prolonged by the slow absorption phase. They were found to be well absorbed after
      subcutaneous administration, with absolute bioavailability being 75.4% and 43.9%,
      respectively. CONCLUSION: With apparent molecular masses not exceeding 43 kDa,
      the conjugates prepared have been and will be demonstrated to have prominent
      advantages for ROP delivery, such as: the good absorption following subcutaneous,
      intramuscular, or other ways of administration; the effective utilization of the
      enhanced permeability and retention effect caused by ischemia; and the rapid
      diffusion within target tissues.

PMID- 22131833
TI  - Antimicrobial activity and the mechanism of silver nanoparticle thermosensitive
      gel.
AB  - PURPOSE: The purpose of the present study was to elucidate the antimicrobial
      activity and mechanism of silver nanoparticles incorporated into thermosensitive
      gel (S-T-Gel) on Staphylococcus aureus, Escherichia coli, and Pseudomonas
      aeruginosa. PATIENTS AND METHODS: This study investigated the growth,
      permeability, and morphology of Staphylococcus aureus, Escherichia coli, and
      Pseudomonas aeruginosa cells in order to observe the action of S-T-Gel on the
      membrane structure of these three bacteria. The cell morphology of normal and
      treated bacteria cells was assessed by transmission electron microscopy (TEM),
      and the effects of S-T-Gel on genome DNA of bacterial cells were evaluated by
      agarose gel electrophoresis. RESULTS: S-T-Gel showed promising activity against
      Staphylococcus aureus and moderate activity against Escherichia coli and
      Pseudomonas aeruginosa. The observation with TEM suggested that S-T-Gel may
      destroy the structure of bacterial cell membranes in order to enter the bacterial
      cell. S-T-Gel then condensed DNA and combined and coagulated with the cytoplasm
      of the damaged bacteria, resulting in the leakage of the cytoplasmic component
      and the eventual death of these three bacteria. In addition, the analysis of
      agarose gel electrophoresis demonstrated that S-T-Gel could increase the
      decomposability of genome DNA. CONCLUSION: These results about promising
      antimicrobial activity and mechanism of S-T-Gel may be useful for further
      research and development in in-vivo studies.

PMID- 22131834
TI  - Hair dye-incorporated poly-gamma-glutamic acid/glycol chitosan nanoparticles
      based on ion-complex formation.
AB  - BACKGROUND: p-Phenylenediamine (PDA) or its related chemicals are used more
      extensively than oxidative hair dyes. However, permanent hair dyes such as PDA
      are known to have potent contact allergy reactions in humans, and severe allergic
      reactions are problematic. METHODS: PDA-incorporated nanoparticles were prepared
      based on ion-complex formation between the cationic groups of PDA and the anionic
      groups of poly(gamma-glutamic acid) (PGA). To reinforce PDA/PGA ion complexes,
      glycol chitosan (GC) was added. PDA-incorporated nanoparticles were characterized
      using field-emission scanning electron microscopy, Fourier- transform infrared
      (FT-IR) spectroscopy, dynamic light scattering, and powder X-ray diffractometry
      (XRD). RESULTS: Nanoparticles were formed by ion-complex formation between the
      amine groups of PDA and the carboxyl groups of PGA. PDA-incorporated
      nanoparticles are small in size (<100 nm), and morphological observations showed
      spherical shapes. FT-IR spectra results showed that the carboxylic acid peak of
      PGA decreased with increasing PDA content, indicating that the ion complexes were
      formed between the carboxyl groups of PGA and the amine groups of PDA.
      Furthermore, the intrinsic peak of the carboxyl groups of PGA was also decreased
      by the addition of GC. Intrinsic crystalline peaks of PDA were observed by XRD.
      This crystalline peak of PDA was completely nonexistent when nanoparticles were
      formed by ion complex between PDA, PGA, and GC, indicating that PDA was complexed
      with PGA and no free drug existed in the formulation. During the drug-release
      experiment, an initial burst release of PDA was observed, and then PDA was
      continuously released over 1 week. Cytotoxicity testing against HaCaT human skin
      keratinocyte cells showed PDA-incorporated nanoparticles had lower toxicity than
      PDA itself. Furthermore, PDA-incorporated nanoparticles showed reduced apoptosis
      and necrosis reaction at HaCaT cells. CONCLUSION: The authors suggest that these
      microparticles are ideal candidates for a vehicle for decreasing side effects of
      hair dye.

PMID- 22131835
TI  - Development and evaluation of pH-responsive single-walled carbon nanotube
      doxorubicin complexes in cancer cells.
AB  - Single-walled carbon nanotubes (SWNTs) have been identified as an efficient drug
      carrier. Here a controlled drug-delivery system based on SWNTs coated with
      doxorubicin (DOX) through hydrazone bonds was developed, because the hydrazone
      bond is more sensitive to tumor microenvironments than other covalent linkers.
      The SWNTs were firstly stabilized with polyethylene glycol (H(2)N-PEG-NH(2)).
      Hydrazinobenzoic acid (HBA) was then covalently attached on SWNTs via
      carbodiimide-activated coupling reaction to form hydrazine-modified SWNTs. The
      anticancer drug DOX was conjugated to the HBA segments of SWNT using hydrazine as
      the linker. The resulting hydrazone bonds formed between the DOX molecules and
      the HBA segments of SWNTs are acid cleavable, thereby providing a strong pH
      responsive drug release, which may facilitate effective DOX release near the
      acidic tumor microenvironment and thus reduce its overall systemic toxicity. The
      DOX-loaded SWNTs were efficiently taken up by HepG2 tumor cells, and DOX was
      released intracellularly, as revealed by MTT assay and confocal microscope
      observations. Compared with SWNT-DOX conjugate formed by supramolecular
      interaction, the SWNT-HBA-DOX featured high weight loading and prolonged release
      of DOX, and thus improved its cytotoxicity against cancer cells. This study
      suggests that while SWNTs have great potential as a drug carrier, the efficient
      formulation strategy requires further study.

PMID- 22131836
TI  - A dynamic magnetic shift method to increase nanoparticle concentration in cancer
      metastases: a feasibility study using simulations on autopsy specimens.
AB  - A nanoparticle delivery system termed dynamic magnetic shift (DMS) has the
      potential to more effectively treat metastatic cancer by equilibrating
      therapeutic magnetic nanoparticles throughout tumors. To evaluate the feasibility
      of DMS, histological liver sections from autopsy cases of women who died from
      breast neoplasms were studied to measure vessel number, size, and spatial
      distribution in both metastatic tumors and normal tissue. Consistent with prior
      studies, normal tissue had a higher vascular density with a vessel-to-nuclei
      ratio of 0.48 +/- 0.14 (n = 1000), whereas tumor tissue had a ratio of 0.13 +/-
      0.07 (n = 1000). For tumors, distances from cells to their nearest blood vessel
      were larger (average 43.8 MUm, maximum 287 MUm, n ~ 5500) than normal cells
      (average 5.3 MUm, maximum 67.8 MUm, n ~ 5500), implying that systemically
      delivered nanoparticles diffusing from vessels into surrounding tissue would
      preferentially dose healthy instead of cancerous cells. Numerical simulations of
      magnetically driven particle transport based on the autopsy data indicate that
      DMS would correct the problem by increasing nanoparticle levels in hypovascular
      regions of metastases to that of normal tissue, elevating the time-averaged
      concentration delivered to the tumor for magnetic actuation versus diffusion
      alone by 1.86-fold, and increasing the maximum concentration over time by 1.89
      fold. Thus, DMS may prove useful in facilitating therapeutic nanoparticles to
      reach poorly vascularized regions of metastatic tumors that are not accessed by
      diffusion alone.

PMID- 22131838
TI  - Things I wish I had been taught about rhinoplasty.

PMID- 22131837
TI  - Embedded nanomicro syringe on chip for molecular therapy.
AB  - BACKGROUND: A novel nanomicro syringe system was proposed for drug storage and
      delivery using a PANDA ring resonator and atomic buffer. A PANDA ring is a
      modified optical add/drop filter, named after the well known Chinese bear. In
      principle, the molecule/drug is trapped by the force generated by different
      combinations of gradient fields and scattering photons within the PANDA ring. A
      nanomicro needle system can be formed by optical vortices in the liquid core
      waveguide which can be embedded on a chip, and can be used for long-term
      treatment. By using intense optical vortices, the required genes/molecules can be
      trapped and transported dynamically to the intended destinations via the
      nanomicro syringe, which is available for drug delivery to target tissues, in
      particular tumors. The advantage of the proposed system is that by confining the
      treatment area, the effect can be decreased. The use of different optical
      vortices for therapeutic efficiency is also discussed.

PMID- 22131840
TI  - Adenoid involvement in velopharyngeal closure in children with cleft palate.
AB  - OBJECTIVE: To assess the role of the adenoid pad in velopharyngeal (VP) closure.
      DESIGN: A retrospective review of patients with cleft palate (CP) who underwent
      nasendoscopy and multiview videofluoroscopy during evaluation for VP
      insufficiency (VPI) from January 2006 to March 2008. PATIENTS: Thirty-two
      consecutive patients were identified. None of the patients were lost to follow
      up. Five patients were excluded: two for advanced age, two due to mental
      disabilities and one with a submucous cleft. INTERVENTION: Video nasendoscopy and
      multiview videofluoroscopy were performed for evaluation of VPI. OUTCOME
      MEASURES: Adenoid size based on nasendoscopy studies, and adenoid involvement in
      VP closure based on videofluoroscopy were recorded. RESULTS: The average patient
      age was 6.6 years (range three to 13 years). Seventy-eight per cent of patients
      had small adenoid volumes (less than 50% obstruction of the choanae), and six
      patients (two unilateral cleft lip and palate patients, one bilateral cleft lip
      and palate patient, two isolated CP patients and one cleft of secondary palate
      patient) had large adenoid volumes (50% or greater obstruction of the choanae);
      the adenoid pads of these patients were almost always (five of six patients)
      involved in their VP closure patterns. Videofluoroscopy showed that 26% (95% CI
      9% to 40%) of patients did not significantly use their adenoid pad in VP closure.
      Forty-three per cent of those not using their adenoids attempted contact with a
      Passavant's ridge. CONCLUSIONS: In general, the adenoid pad should be maintained
      in CP patients. However, not all CP patients in the present study used their
      adenoid pad in attempted VP closure. If adenoidectomy is medically indicated, a
      percentage of these patents might be considered to be at lower risk for the
      development of postadenoidectomy VPI.

PMID- 22131839
TI  - Keyhole pattern for preoperative marking for reduction mammaplasty.
AB  - BACKGROUND: There are many techniques used for reduction mammaplasty; however,
      the most frequently performed procedures result in an inverted T scar.
      Preoperative marking is an important step for the success of the procedure,
      especially for surgeons at the initial learning stage. However, there is no
      consensus regarding the best method. In 1981, Strombeck designed a pattern for
      preoperative marking for reduction mammaplasty. This pattern provides stable
      parameters that promotes an acceptable symmetry marking. OBJECTIVE: To evaluate
      the use of the Strombeck pattern for preoperative marking for reduction
      mammaplasty. METHODS: Fifty-seven patients who underwent reduction mammaplasty
      between April 2006 and April 2007 were prospectively evaluated. Patient ages
      ranged from 17 to 61 years; the mean body mass index was 22.2 kg/m(2). After
      defining the standard landmarks of the breast, preoperative markings were made
      using the Strombeck pattern. Breast reduction surgery was performed under local
      anesthesia with sedation. Postoperative results were evaluated according to a
      numerical visual analogue scale, at the seven-, 15- and 30-day follow-up periods.
      The Student's t test and the Kruskal-Wallis test were used for statistical
      analysis (P<0.05). RESULTS: The mean weight of resected breast tissue was 317.5 g
      for the right breast and 305.8 g for the left breast (P=0.17). Scores obtained
      using a visual analogue scale showed a progressive increase in the scores during
      the postoperative follow-up period (P<0.0001). CONCLUSION: The use of the
      Strombeck pattern enabled surgeons to perform reduction mammaplasty with good
      postoperative results as seen in the follow-up periods.

PMID- 22131841
TI  - Vacuum-assisted closure as a surgical assistant in life-threatening necrotizing
      fasciitis in children.
AB  - Necrotizing fasciitis is a severe soft tissue infection that can involve skin,
      subcutaneous fat, fascia and muscle. It can result in devastating sequelae
      including tissue necrosis, sepsis, toxic shock syndrome, cardiopulmonary collapse
      and death. To control rapidly spreading necrosis, early diagnosis and aggressive
      surgical treatment with extensive radical debridement of the affected areas is
      necessary, as well as systemic administration of broad-spectrum antimicrobials
      and, very often, intensive care support.The subatmospheric negative pressure
      dressing has been previously used in acute and complex wounds management. The
      concept of using vacuum-assisted closure dressing as another management component
      is presented in the current article.

PMID- 22131842
TI  - Reconstruction of a congenitally absent flexor pollicis longus in an adult.
AB  - Congenital absence of the flexor pollicis longus (FPL) is an unusual finding that
      is frequently associated with thumb hypoplasia. Isolated FPL absence is the
      rarest of the congenital thumb anomalies. The present article describes a patient
      with a congenitally absent FPL, and discusses the chosen method of
      reconstruction.

PMID- 22131843
TI  - Bilateral and multifocal phyllodes tumours of the breast: A case report.
AB  - Phyllodes tumours are rare breast neoplasms that present as painless breast
      masses. They are classified as benign, malignant and borderline. More rare
      presentations of these tumours include bilateral asynchronous disease and
      unilateral multifocal disease. Surgical excision with clear margins remains the
      treatment of choice for these tumours. The present case report is the first to be
      discussed in the literature. It describes a patient presenting with synchronous
      bilateral, multifocal breast phyllodes tumours who underwent immediate
      reconstruction with tissue expanders at the time of her mastectomies.

PMID- 22131844
TI  - Umbilical endometriosis: A rare diagnosis in plastic and reconstructive surgery.
AB  - Umbilical endometriosis infrequently presents to the plastic surgeon. As such,
      the diagnosis is difficult to make because it is often overlooked. The current
      report presents a 35-year-old nulligravid woman with a six-month history of a
      firm, cyclically swelling lesion in her umbilical region. None of the signs
      characteristic of pelvic endometriosis except dysmenorrhea and a one-year history
      of infertility were present. Biopsy of the lesion revealed umbilical
      endometriosis (grade IV), and laparoscopy uncovered extensive disease. Monopolar
      cautery with coagulating current umbilical excision and reconstruction with a
      purse-string suture was used. The results underscore the importance of a broad
      differential diagnosis for an umbilical lesion in a middle-age woman. They also
      highlight the importance of early recognition and appropriate surgical
      intervention to minimize morbidity and mortality associated with umbilical
      endometriosis.

PMID- 22131845
TI  - Reconstruction of a full-thickness alar wound using an auricular conchal
      composite graft.
AB  - Nasogastric intubation has become a frequently used method for alleviating
      gastrointestinal symptoms. Necrosis from alar pressure during prolonged
      nasogastric and nasotracheal intubation is common, and can result in considerable
      deformity if it is unrecognized. The reconstruction of full-thickness alar wounds
      often requires multiple challenging surgical procedures. Difficult full-thickness
      alar defects often require nasal mucosal replacement for lining, cartilage batten
      graft support for the preservation of nasal function, and skin coverage for the
      restoration of an aesthetically correct appearance. Free composite conchal
      grafting can offer a single-staged, one-step repair of difficult full-thickness
      alar wounds that are no larger than 1.5 cm in size. A thorough explanation of the
      graft design and execution is presented, as well as a case report and literature
      review. Free composite conchal grafting can produce aesthetic and functional
      results that rival the most sophisticated flap reconstructions of the lateral
      ala.

PMID- 22131846
TI  - Breast augmentation: A geographical comparison.
AB  - OBJECTIVE: To describe and compare physical characteristics and implant details
      of women undergoing primary cosmetic breast augmentation in different
      geographical locations. METHODS: Three cohorts of 100 consecutive breast
      augmentation cases in university settings were retrospectively reviewed for
      patient demographic and implant information in Kelowna (British Columbia), Loma
      Linda (California, USA) and Temple (Texas, USA). Statistical analysis was
      performed with a Kruskal-Wallis test without normality assumption (P<0.05 was
      considered to be significant). Pearson correlation coefficients were also
      determined for body mass index (BMI) versus implant volume at each of the sites.
      RESULTS: The three group medians were significantly different for weight, BMI and
      implant volume. Kelowna's average patient was 33 years of age, had a BMI of 20.8
      kg/m(2) and an implant volume of 389 mL. Loma Linda's average patient was 32
      years of age, had a BMI of 21.6 kg/m(2) and an implant volume of 385 mL. Temple's
      average patient was 36 years of age, had a BMI of 22.6 kg/m(2) and an implant
      volume of 335 mL. Pearson correlations for BMI versus implant volume were
      statistically significant in the Loma Linda and Temple groups. CONCLUSION:
      Patients from different geographical locations undergoing breast augmentation
      were similar in age, height and parity, but varied in weight, BMI and implant
      volume. A positive linear correlation between BMI and implant volume was found in
      the American cohorts.

PMID- 22131847
TI  - Making the V-Y advancement flap safer in fingertip amputations.
AB  - Amputation of the fingertip is a common injury of the upper extremity. Over the
      years, a variety of reconstructive techniques have been described. For dorsal
      oblique and transverse amputations, the Atasoy V-Y advancement flap is a popular
      choice because it preserves finger length, sensation and function. However,
      closure under tension remains a problem, putting the flap at risk of partial or
      full necrosis. To avoid this untoward complication, the classic V-Y advancement
      technique has been modified to allow for a tension-free closure.

PMID- 22131848
TI  - Bilateral pulmonary emboli after bilateral mastectomy in a 15-year-old boy with
      hypogonadism: A case report.
AB  - Pulmonary emboli are rare, yet serious, complications of body contouring surgery.
      When they occur, they more often follow as complications of long, invasive
      procedures in adults. The present report details a case of bilateral pulmonary
      emboli in an obese 15-year-old boy with hypogonadism undergoing bilateral
      mastectomy for gynecomastia. The diagnosis of bilateral pulmonary emboli was made
      on the basis of clinical presentation and positive ventilation/perfusion scan.
      The patient responded well to heparin anticoagulation treatment. The relevance of
      pediatric obesity, pediatric body contouring surgery and the risk of
      thromboembolic events in pediatric patients are discussed.

PMID- 22131850
TI  - A tribute to Dr Pawan K Singal on his 65th birthday.

PMID- 22131849
TI  - A case of autologous microfat grafting in lip reconstruction of a whistle
      deformity following cancer treatment.
AB  - A whistle deformity is defined as a deficiency in the vertical length of the lip
      so that the free margins of the upper and lower lips do not meet normally, giving
      the appearance of whistling. This is a common secondary deformity of the
      vermilion in patients with cleft lip. A case involving a 61-year-old man who
      developed a whistle deformity as a result of two wedge resections and
      postoperative radiotherapy for treatment of squamous cell carcinoma of the lower
      lip is presented. Hyaluronic acid-based tissue filler and autologous microfat
      transplantation to the lower lip were used for definitive management of the
      patient's whistle deformity. After one year of follow-up, the patient was pleased
      with the overall result and noted marked improvement of his oral competence and
      overall appearance of the lip. The present case demonstrates that microfat
      transplantation is a viable option for correcting a whistle deformity, not only
      after surgery, but also following adjuvant radiotherapy - both of which
      potentially reduce graft viability secondary to decreased vascularity of the
      recipient site.

PMID- 22131852
TI  - Intracellular calcium overloading and oxidative stress in cardiomyocyte necrosis
      via a mitochondriocentric signal-transducer-effector pathway.
AB  - Congestive heart failure (CHF), a common clinical syndrome, has reached epidemic
      proportions. Its disabling symptoms account for frequent hospitalizations and
      readmissions. Pathophysiological mechanisms that lead to CHF and account for its
      progressive nature are of considerable interest. Important scientific
      observations obtained from Dr Pawan K Singal's laboratory in Winnipeg, Manitoba,
      have provided crucial insights to our understanding of the pathophysiological
      factors that contribute to cardiomyocyte necrosis (the heart is a postmitotic
      organ incapable of tolerating an ongoing loss of these cells without adverse
      functional consequences). This increment in knowledge and the mechanistic
      insights afforded by Dr Singal and his colleagues have highlighted the role of
      excessive intracellular calcium accumulation and the appearance of oxidative
      stress in CHF, in which the rate of reactive oxygen species generation overwhelms
      their rate of detoxification by antioxidant defenses. They have shown that this
      common pathophysiological scenario applies to diverse entities such as
      ischemia/reperfusion and hypoxia/reoxygenation forms of injury, myocardial
      infarction and the cardiomyopathies that accompany diabetes and excess levels of
      catecholamines and adriamycin. The authors are honoured to be invited to
      contribute to the present focus issue of Experimental & Clinical Cardiology in
      recognizing Dr Singal's numerous scholarly accomplishments. The present article
      reviews the authors' recent work on a mitochondriocentric signal-transducer
      effector pathway to cardiomyocyte necrosis found in rats with either an acute
      stressor state that accompanies isoproterenol administration or a chronic
      stressor state manifested after four weeks of aldosterone/salt treatment.

PMID- 22131851
TI  - Cell death signalling mechanisms in heart failure.
AB  - Cardiac disease is a global epidemic that is on the rise, despite the recent
      advances in cardiovascular research. Once the myocardium is injured, it has a
      limited capacity to activate reparative mechanisms to restore proper cardiac
      function, leading to the development of systemic heart failure. Autophagy, under
      certain conditions, may result in cell death, further emphasizing the
      controversial issues regarding the autophagic process as an adaptive or
      maladaptive biological response. Although significant progress in understanding
      the signalling mechanisms of cell death in myocytes has been made, the role of
      apoptotic cell death and programmed necrosis during heart failure is not
      completely understood. Insight to how myocytes determine whether to activate
      apoptotic or programmed necrosis signalling machinery remains under current
      investigation because it is a major problem for both scientists and clinicians in
      treating heart failure patients. Herein, the different modes of cell death
      implicated in heart failure are highlighted, as well as the role of B-cell
      lymphoma-2 family members and how mitochondria act as central organelles in
      directing such cell death mechanisms.

PMID- 22131853
TI  - Alterations of the intercellular coupling protein, connexin-43, during
      ventricular fibrillation and sinus rhythm restoration demonstrated in male and
      female rat hearts: A pilot study.
AB  - Ventricular fibrillation (VF) is a life-threatening arrhythmia, whose occurrence
      precedes the development of myocardial arrhythmogenic substrate resulting from
      either chronic or acute pathophysiological conditions. The authors' previous and
      current studies suggest that downregulated and/or heterogeneously distributed
      cell-to-cell coupling protein - connexin-43 (Cx43) - facilitates the development
      of malignant arrhythmias. It was hypothesized that VF itself deteriorates Cx43,
      and may hamper cardioversion into sinus rhythm. The purpose of the present study
      was to examine whether myocardial expression and the phosphorylated status of
      Cx43 is altered due to VF and during sinus rhythm restoration. Experiments were
      performed using 10-month-old male and female Wistar rats. Isolated Langendorff
      mode-perfused rat hearts were subjected to the following events: basal condition,
      electrically induced VF lasting 2 min, electrically induced VF lasting 10 min,
      and sustained VF followed by spontaneous sinus rhythm restoration due to
      transient stop perfusion. The hearts were snap frozen at each event; ventricular
      tissue was sent for Cx43 immunoblotting using rabbit antiCx43 polyclonal antibody
      to detect phosphorylated (P-Cx43) as well as unphosphorylated (noP-Cx43) forms of
      Cx43, and mouse antiCx43 monoclonal antibody to detect noP-Cx43 only. Compared
      with basal conditions, total Cx43 expression did not change during experiments in
      either male or female rat hearts. However, P-Cx43 and the ratio of P-Cx43 to
      total Cx43 decreased significantly due to VF lasting 2 min and 10 min in male rat
      hearts only. In parallel, there was a significant increase in noP-Cx43 due to VF
      lasting 2 min and 10 min in male rat hearts only. Surprisingly, an enhancement of
      noP-Cx43 linked with suppression of P-Cx43 was detected during stop perfusion
      induced termination of VF lasting 2 min, followed by sinus rhythm restoration in
      both male and female rat hearts. Sinus rhythm was not restored after 10 min of
      VF, which caused pronounced Cx43 dephosphorylation. In conclusion, there is a
      downregulation of Cx43 due to sustaining of VF, and it occurs earlier in male rat
      hearts compared with female rat hearts. It appears that transient no-flow-related
      inhibition of cell-to-cell coupling, as indicated by an increase in nonP-Cx43,
      can terminate VF followed by sinus rhythm restoration depending on the degree of
      previous Cx43 downregulation.

PMID- 22131854
TI  - Loss of neutral endopeptidase activity contributes to neutrophil activation and
      cardiac dysfunction during chronic hypomagnesemia: Protection by substance P
      receptor blockade.
AB  - BACKGROUND/OBJECTIVE: Hypomagnesemia (Hypo-Mg) in rodents leads to neurogenic
      inflammation associated with substance P (SP) elevations; neutral endopeptidase
      (NEP) is a principle cell surface proteolytic enzyme, which degrades SP. The
      effects of chronic Hypo-Mg on neutrophil NEP activity, cell activation and the
      associated cardiac dysfunction were examined. METHODS/RESULTS: Male Sprague
      Dawley rats (180 g) were fed Mg-sufficient or Mg-deficient (Hypo-Mg) diets for
      five weeks. Enriched blood neutrophils were isolated at the end of one, three and
      five weeks by step gradient centrifugation. NEP enzymatic activity decreased by
      20% (P value was nonsignificant), 50% (P<0.025) and 57% (P<0.01), respectively,
      for week 1, 3 and 5 Hypo-Mg rats. In association, neutrophil basal superoxide
      (*O(2) (-))-generating activities were elevated: 30% at week 1 (P value was
      nonsignificant), and fourfold to sevenfold for weeks 3 to 5 (P<0.01). Maximal
      phorbol myristate acetate-stimulated *O(2) (-) production by Hypo-Mg neutrophils
      increased twofold at week 5. Also, plasma 8-isoprostane levels were elevated
      twofold to threefold, and red blood cell glutathione decreased by 50% (P<0.01)
      after three to five weeks of chronic Hypo-Mg. When Hypo-Mg rats were treated with
      the SP receptor blocker (L-703,606), neutrophil NEP activities were retained at
      75% (week 3) and 77% (week 5) (P<0.05); activation of neutrophil *O(2) (-) and
      other oxidative indexes were also significantly (P<0.05) attenuated. After five
      weeks, histochemical (hematoxylin and eosin) staining of Hypo-Mg-treated rat
      ventricles revealed significant white blood cell infiltration, which was
      substantially reduced by L-703,606. Echocardiography after three weeks of Hypo-Mg
      only showed modest diastolic impairment, but five weeks resulted in significant
      (P<0.05) depression in both left ventricular systolic and diastolic functions;
      changes in these functional parameters were attenuated by L-703,606. CONCLUSION:
      NEP activity regulates neutrophil *O(2) (-) formation by controlling SP
      bioavailability. When oxidative inactivation of NEP is prevented by SP receptor
      blockade, partial protection is afforded against cardiac contractile dysfunction.

PMID- 22131855
TI  - Role of mitochondrial permeability transition in taurine deficiency-induced
      apoptosis.
AB  - It has recently been shown that taurine deficiency leads to impaired respiratory
      chain function, resulting in reduced ATP generation and enhanced oxidative
      stress. Because cardiomyopathy develops in taurine-deficient animals, the
      hypothesis that mitochondrial oxidative stress may contribute to the development
      of cardiomyocyte dysfunction and cell death was tested. Isolated neonatal
      cardiomyocytes incubated in medium containing the taurine transport inhibitor,
      beta-alanine, lost nearly one-half of their cellular taurine content after 48 h.
      Accompanying the loss of taurine was a time-dependent increase in apoptosis,
      which was prevented by the mitochondrial permeability transition inhibitor,
      cyclosporin A. Two taurine-dependent factors, oxidative stress and calcium
      overload, serve as important regulators of the mitochondrial permeability
      transition. Although taurine deficiency slowed the removal of calcium from the
      cytosol, it had no effect on diastolic calcium content and only modestly reduced
      systolic calcium content, suggesting that calcium overload is not the trigger for
      mitochondrial permeability transition pore formation. On the other hand, the
      glutathione redox ratio was significantly altered in the taurine-deficient
      cardiomyocyte, suggesting that oxidative stress is the primary initiator of
      mitochondrial permeability transition and apoptosis in the taurine-deficient
      cardiomyocyte.

PMID- 22131856
TI  - Emerging new uses of phosphodiesterase-5 inhibitors in cardiovascular diseases.
AB  - Phosphodiesterase type-5 (PDE-5) is an enzyme that catalyzes the hydrolytic
      degradation of cyclic GMP - an essential intracellular second messenger that
      modulates diverse biological processes in living cells. Three selective
      inhibitors of PDE-5 - sildenafil, vardenafil and tadalafil - have been
      successfully used by millions of men worldwide for the treatment of erectile
      dysfunction. Also, sildenafil and tadalafil are currently approved for the
      treatment of pulmonary hypertension. Recent powerful basic science data and
      clinical studies suggest potential nonurological applications of PDE-5
      inhibitors, including ischemia/reperfusion injury, myocardial infarction, cardiac
      hypertrophy, cardiomyopathy, heart failure, stroke, neurodegenerative diseases
      and other circulatory disorders including Raynaud's phenomenon. Future carefully
      controlled clinical trials would hopefully expedite their expanding therapeutic
      use in patients with cardiovascular disease.

PMID- 22131857
TI  - Cystathionine gamma-lyase-deficient smooth muscle cells exhibit redox imbalance
      and apoptosis under hypoxic stress conditions.
AB  - BACKGROUND: Hydrogen sulphide (H(2)S) has recently emerged as a novel and
      important gasotransmitter in the cardiovascular system, where it is generated
      mainly by cystathionine gamma-lyase (CSE). Abnormal metabolism and functions of
      the CSE/H(2)S pathway have been linked to various cardiovascular diseases
      including atherosclerosis and hypertension. An important role for H(2)S in
      regulating the balance between cellular growth and death has been demonstrated
      whereby inhibition of the endogenous CSE/H(2)S pathway results in greater
      apoptosis of vascular smooth muscle cells (SMCs). H(2)S is increasingly
      recognized as a critical regulator of vascular integrity, but its role in SMCs
      during hypoxia has not been explored in a model of CSE deficiency. METHODS: Cell
      viability, apoptosis, redox status and mitochondrial activity in hypoxia-exposed
      (12 h at 1% O(2)) SMCs derived from the mesenteric artery of CSE-knockout (CSE
      KO) mice were analyzed. These were compared with those from CSE-wild-type (CSE
      WT) mice. RESULTS: CSE-KO cells exhibited redox imbalance and aberrant
      mitochondrial activity versus CSE-WT cells, indicating an essential regulatory
      role for the endogenous CSE/H(2)S pathway on SMC function. CSE-KO cells were also
      more susceptible to hypoxia-induced cell death, indicating a critical
      contribution of endogenous CSE/H(2)S pathway to the protective hypoxia stress
      response. CONCLUSION: These findings support the concept that H(2)S is a crucial
      regulator of vascular homeostasis, the deficiency of which is associated with
      various pathologies, and provide further evidence that H(2)S is a potent
      vasculoprotectant.

PMID- 22131859
TI  - Canadian Paediatric Surveillance Program 2010 quiz.

PMID- 22131858
TI  - Letter to the editor.

PMID- 22131860
TI  - Reflections of a slow learner.

PMID- 22131861
TI  - Streptococcal pharyngitis - time to move beyond penicillins?

PMID- 22131862
TI  - Jewellery- and ornament-related injuries in children and adolescents.
AB  - BACKGROUND: Unintentional injuries are the leading cause of mortality and
      morbidity in children and teenagers in Canada. Few publications have addressed
      injuries caused by jewellery and ornaments in children. OBJECTIVES: To examine
      the mechanisms and the incidence of injuries caused by jewellery and ornaments in
      children and teenagers, to identify children at high risk for these type of
      injuries and to recommend specific injury prevention strategies. METHODS: Data
      were analyzed from a Canadian database (Canadian Hospitals Injury Reporting and
      Prevention Program) of a tertiary paediatric centre. All patients between zero
      and 18 years of age who were diagnosed in the emergency department with jewellery
      and ornament-related injuries during a 10-year period (1997 to 2006) were
      identified. Patients were categorized according to six age groups (younger than
      one year of age; one to two years of age; two to four years of age; five to nine
      years of age; 10 to 14 years of age, and 15 to 18 years of age). For each case,
      the context and the mechanism of injury were investigated. RESULTS: From a total
      of 150,771 reported injury cases, 380 (0.25%) were jewellery related. Unlike with
      most trauma, girls predominate in this kind of injury (n=288; 75.8% of cases).
      Over one-half of cases (58.1%) were reported for children four years of age or
      younger. Emergency physicians reported the presence of jewellery as a foreign
      body in a natural orifice (mouth, nose, ear or genitourinary tract) in 308 cases
      (81%). No case of intestinal obstruction, strangulation or death was reported.
      Eleven cases (2.9%) required emergency hospitalization, all for endoscopic
      evaluation of a foreign body in the airway or in the digestive tract. In the
      adolescent group, five cases of injuries secondary to piercing were reported.
      CONCLUSION: The present study demonstrates that, although jewellery-related
      injuries are relatively infrequent, some can cause severe injuries that could
      compromise patients' health. As a primary prevention strategy, doctors and health
      professionals working with children should make parents and caregivers aware of
      the possibility of trauma in children wearing or playing with jewellery,
      especially in the zero- to four-year-old group requiring closer supervision.
      Specific anticipatory guidance concerning piercing may be helpful to adolescents.

PMID- 22131863
TI  - Parents' compliance with specific medical instructions in newborn discharge
      letters.
AB  - BACKGROUND: Due to decreased hospital stay, follow-up of unresolved medical
      problems of babies with uncomplicated postpartum course is relegated to
      outpatient clinics. OBJECTIVE: To identify factors in discharge letters that
      influence parent compliance. METHODS: Telephone contact with parents three months
      after discharge queried compliance with routine and special instructions as
      written in discharge letters. Statistical analyses compared responses of
      compliant versus less compliant parents. P<0.05 was considered to be
      statistically significant. The present study was approved by the Institutional
      Ethical Review Board Committee. RESULTS: Of the 2000 discharge letters, 319 (16%)
      included special instructions. Parents of 252 infants (79%) who received
      discharge letters containing 332 special instructions were interviewed by
      telephone. Compliance was greater for noninvasive instructions (86%) relative to
      others (57.8%) (P<0.001). Initiation of follow-up visits was correlated with
      parity (P<0.001) and maternal age (P<0.001). CONCLUSION: Discharge letters should
      be read and discussed with parents before infants are discharged, and the
      relevance of specific medical instructions should be emphasized.

PMID- 22131864
TI  - Letter to the editor.

PMID- 22131865
TI  - Safe discharge of the late preterm infant.
AB  - Late preterm infants are infants who are premature, but often mature enough to be
      managed in settings and with treatment plans appropriate for term newborns. They
      are arbitrarily defined as infants born at gestational ages of 34, 35 and 36
      weeks. Late preterm infants have more problems with adaptation than term infants,
      and may require neonatal intensive care and prolonged admission. However, those
      who do not may, appropriately, be triaged to mother-baby care in a low-risk
      nursery setting. Special attention must be offered to the late preterm infant in
      ensuring adequate thermal homeostasis and the establishment of successful feeding
      before discharge. In particular, care must be taken to ensure that these babies
      do not experience severe late hyperbilirubinemia, which characteristically occurs
      in the breastfeeding late preterm infant at four to five days of age and is not
      always predictable by routine bilirubin screening before 48 h of age. Discharge
      of a late preterm infant places particular demands on the community; accessible
      facilities for retesting, re-evaluation and readmission must be made available by
      the discharging institution.

PMID- 22131866
TI  - Retinopathy of prematurity: Recommendations for screening.
AB  - Retinopathy of prematurity (ROP) is a disorder of the developing retinal blood
      vessels of the preterm infant. New recommendations for screening and treatment of
      ROP have been published in the past few years. Current evidence suggests that
      screening infants with gestational ages of 30 6/7 weeks or less (regardless of
      birth weight) and birth weights of 1250 g or less is a strategy with a very small
      likelihood that an unscreened baby would have treatable ROP. Individual centres
      may choose to extend birth weight screening criteria to 1500 g. Initial screening
      should be performed at 31 weeks' postmenstrual age in infants with gestational
      ages of 26 6/7 weeks or less at birth, and at four weeks' chronological age in
      infants with gestational ages of 27 weeks or more at birth by an ophthalmologist
      skilled in the detection of ROP. Follow-up examinations are conducted according
      to the ophthalmologist's recommendation. Infants with high-risk prethreshold ROP
      and threshold ROP are referred for retinal ablative therapy. Developing processes
      for ROP screening, documenting results and communicating results to parents as
      well as health professionals involved in the infant's care are important
      responsibilities for all nurseries providing care for preterm infants.

PMID- 22131867
TI  - Practising what we preach: A look at healthy active living policy and practice in
      Canadian paediatric hospitals.
AB  - BACKGROUND: In the past 30 years, the rate of obesity has risen considerably
      among Canadian children. Paediatric hospitals are in a unique position to model
      healthy environments to Canadian children. OBJECTIVE: To obtain an overview of
      healthy active living (HAL) policy and practice in Canadian paediatric hospitals.
      METHODS: Working in partnership with the local Canadian Paediatric Society HAL
      champions and the Canadian Association of Paediatric Health Centres liaisons, a
      nationwide survey was conducted in 2006/2007 to identify healthy eating, physical
      activity and smoking cessation practices in all 16 Canadian paediatric academic
      hospitals. RESULTS: Policies addressing healthy eating and/or physical activity
      promotion were present in 50% of hospitals with a greater focus on nutrition.
      Wellness committees were created in 50% of the hospitals, most of which were
      recently established. Healthy food options were available in cafeterias, although
      they were often more expensive. Fast food outlets were present in 75% of
      hospitals. Although inpatient meals were designed by dietitians, 50% offered less
      nutritious replacement kids meals (ie, meal substitutions) on request. Options
      for play available to inpatients and outpatients were primarily sedentary, with
      screen-based activities and crafts predominating over active play. Physical
      activity promotion for staff focused on reduced membership fees to fitness
      centres and classes. CONCLUSION: Canadian paediatric hospitals do not adequately
      promote HAL for patients and staff. The present study findings suggest further
      effort is required to create necessary healthy lifestyle modifications in these
      institutions through Canadian Paediatric Society/Canadian Association of
      Paediatric Health Centres-led policy development and implementation initiatives.
      A national-level policy framework is required to regulate interhospital
      variability in policies and practices.

PMID- 22131868
TI  - Clinics, epidemiology and genetics of retinitis pigmentosa.

PMID- 22131869
TI  - Retinitis pigmentosa: genes and disease mechanisms.
AB  - Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000
      7000 people and characterized by abnormalities of the photoreceptors (rods and
      cones) or the retinal pigment epithelium of the retina which lead to progressive
      visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or
      X-linked manner. While usually limited to the eye, RP may also occur as part of a
      syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have
      been associated with RP so far, with the majority of them expressed in either the
      photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of
      the disease makes the genetics of RP complicated, thus rendering genotype
      phenotype correlations not fully applicable yet. In addition to the multiplicity
      of mutations, in fact, different mutations in the same gene may cause different
      diseases. We will here review which genes are involved in the genesis of RP and
      how mutations can lead to retinal degeneration. In the future, a more thorough
      analysis of genetic and clinical data together with a better understanding of the
      genotype-phenotype correlation might allow to reveal important information with
      respect to the likelihood of disease development and choices of therapy.

PMID- 22131870
TI  - Clinical and Rehabilitative Management of Retinitis Pigmentosa: Up-to-Date.
AB  - The term retinitis pigmentosa (RP) indicates a heterogeneous group of genetic
      rare ocular diseases in which either rods or cones are prevalently damaged. RP
      represents the most common hereditary cause of blindness in people from 20 to 60
      years old. In general, the different RP forms consist of progressive photo
      receptorial neuro-degenerations, which are characterized by variable visual
      disabilities and considerable socio-sanitary burden. Sometimes, RP patients do
      not become visually impaired or legally blind until their 40-50 years of age
      and/or maintain a quite acceptable sight for all their life. Other individuals
      with RP become completely blind very early or in middle childhood. Although there
      is no treatment that can effectively cure RP, in some case-series the disease's
      progression seems to be reducible by specific preventive approaches. In the most
      part of RP patients, the quality of vision can be considerably increased by means
      of nanometer-controlled filters. In the present review, the main aspects of the
      routine clinical and rehabilitative managements for RP patients are described,
      particularly focusing on the importance of specific referral Centers to practice
      a real multidisciplinary governance of these dramatic diseases.

PMID- 22131871
TI  - Good epidemiologic practice in retinitis pigmentosa: from phenotyping to
      biobanking.
AB  - Inherited retinal dystrophies, such as retinitis pigmentosa (RP), include a group
      of relatively rare hereditary diseases caused by mutations in genes that code for
      proteins involved in the maintenance and function of the photoreceptor cells
      (cones and rods). The different forms of RP consist of progressive
      neurodegenerative disorders which are generally related to various and severe
      limitations of visual performances. In the course of typical RP (rod-cone
      dystrophy), the affected individuals first experience night-blindness and/or
      visual field constriction (secondary to rod dysfunctions), followed by variable
      alterations of the central vision (due to cone damages). On the other hand,
      during the atypical form of RP (cone-rod dystrophy), the cone's functionalities
      are prevalently disrupted in comparison with the rod's ones. The basic diagnosis
      of RP relies upon the documentation of unremitting loss in photoreceptor activity
      by electroretinogram and/or visual field testing. The prevalence of all RP
      typologies is variably reported in about one case for each 3000-5000 individuals,
      with a total of about two millions of affected persons worldwide. The inherited
      retinal dystrophies are sometimes the epiphenomenon of a complex framework
      (syndromic RP), but more often they represent an isolated disorder (about 85-90 %
      of cases). Although 200 causative RP mutations have been hitherto detected in
      more than 100 different genes, the molecular defect is identifiable in just about
      the 50% of the analyzed patients with RP. Not only the RP genotypes are very
      heterogeneous, but also the patients with the same mutation can be affected by
      different phenotypic manifestations. RP can be inherited as autosomal dominant,
      autosomal recessive or X-linked trait, and many sporadic forms are diagnosed in
      patients with no affected relatives. Dissecting the clinico-genetic complexity of
      RP has become an attainable objective by means of large-scale research projects,
      in which the collaboration between ophthalmologists, geneticists, and
      epidemiologists becomes a crucial aspect. In the present review, the main issues
      regarding clinical phenotyping and epidemiologic criticisms of RP are focused,
      especially highlighting the importance of both standardization of the diagnostic
      protocols and appropriateness of the disease's registration systems.

PMID- 22131872
TI  - Diagnostic challenges in retinitis pigmentosa: genotypic multiplicity and
      phenotypic variability.
AB  - Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal
      disorders. Diagnosis can be challenging as more than 40 genes are known to cause
      non-syndromic RP and phenotypic expression can differ significantly resulting in
      variations in disease severity, age of onset, rate of progression, and clinical
      findings. We describe the clinical manifestations of RP, the more commonly known
      causative gene mutations, and the genotypic-phenotypic correlation of RP.

PMID- 22131873
TI  - Therapeutic challenges to retinitis pigmentosa: from neuroprotection to gene
      therapy.
AB  - Syndromic retinitis pigmentosa (RP) is the result of several mutations expressed
      in rod photoreceptors, over 40 of which have so far been identified. Enormous
      efforts are being made to relate the advances in unraveling the patho
      physiological mechanisms to therapeutic approaches in animal models, and
      eventually in clinical trials on humans. This review summarizes briefly the
      current clinical management of RP and focuses on the new exciting treatment
      possibilities. To date, there is no approved therapy able to stop the evolution
      of RP or restore vision. The current management includes an attempt at slowing
      down the degenerative process by vitamin supplementation, trying to treat ocular
      complications and to provide psychological support to blind patients. Novel
      therapeutic may be tailored dependant on the stage of the disease and can be
      divided in three groups. In the early stages, when there are surviving
      photoreceptors, the first approach would be to try to halt the degeneration by
      correction of the underlying biochemical abnormality in the visual cycle using
      gene therapy or pharmacological treatment. A second approach aims to cope with
      photoreceptor cell death using neurotrophic growth factors or anti-apoptotic
      factors, reducing the production of retino-toxic molecules, and limiting
      oxidative damage. In advanced stages, when there are few or no functional
      photoreceptors, strategies that may benefit include retinal transplantation,
      electronic retinal implants or a newly described optogenetic technique using a
      light-activated channel to genetically resensitize remnant cone-photoreceptor
      cells.

PMID- 22131874
TI  - Keeping the balance between proliferation and differentiation: the primary
      cilium.
AB  - Primary cilia are post-mitotic cellular organelles that are present in the vast
      majority of cell types in the human body. An extensive body of data gathered in
      recent years is demonstrating a crucial role for this organelle in a number of
      cellular processes that include mechano and chemo-sensation as well as the
      transduction of signaling cascades critical for the development and maintenance
      of different tissues and organs. Consequently, cilia are currently viewed as
      cellular antennae playing a critical role at the interphase between cells and
      their environment, integrating a range of stimuli to modulate cell fate decisions
      including cell proliferation, migration and differentiation. Importantly, this
      regulatory role is not just a consequence of their participation in signal
      transduction but is also the outcome of both the tight synchronization/regulation
      of ciliogenesis with the cell cycle and the role of individual ciliary proteins
      in cilia-dependent and independent processes. Here we review the role of primary
      cilia in the regulation of cell proliferation and differentiation and illustrate
      how this knowledge has provided insight to understand the phenotypic consequences
      of ciliary dysfunction.

PMID- 22131875
TI  - Paramutation: just a curiosity or fine tuning of gene expression in the next
      generation?
AB  - Gene silencing is associated with heritable changes in gene expression which
      occur without changes in DNA sequence. In eukaryotes these phenomena are common
      and control important processes, such as development, imprinting, viral and
      transposon sequence silencing, as well as transgene silencing. Among the
      epigenetic events, paramutation occurs when a silenced allele (named
      paramutagenic) is able to silence another allele (paramutable) in trans and this
      change is heritable. The silenced paramutable allele acquires paramutagenic
      capacity in the next generations. In the 1950s, Alexander Brink described for the
      first time the phenomenon of paramutation, occurring in maize at the colored1
      (r1) gene, a complex locus (encoding myc-homologous transcription factors) that
      regulates the anthocyanin biosynthetic pathway. Since then, paramutation and
      paramutation-like interactions have been discovered in other plants and animals,
      suggesting that they may underlie important mechanisms for gene expression. The
      molecular bases of these phenomena are unknown. However in some cases, the event
      of paramutation has been correlated with changes in DNA methylation, chromatin
      structure and recently several studies suggest that RNA could play a fundamental
      role. This last consideration is greatly supported by genetic screening for
      mutants inhibiting paramutation, which allowed the identification of genes
      involved in RNA-directed transcriptional silencing, although it is possible that
      proteins are also required for paramutation.The meaning of paramutation in the
      life cycle and in evolution remains to be determined even though we might
      conjecture that this phenomenon could be involved in a fast heritability of
      favourable epigenetic states across generations in a non-Mendelian way.

PMID- 22131876
TI  - Conditional expression of oncogenic C-RAF in mouse pulmonary epithelial cells
      reveals differential tumorigenesis and induction of autophagy leading to tumor
      regression.
AB  - Here we describe a novel conditional mouse lung tumor model for investigation of
      the pathogenesis of human lung cancer. On the basis of the frequent involvement
      of the Ras-RAF-MEK-ERK signaling pathway in human non-small cell lung carcinoma
      (NSCLC), we have explored the target cell availability, reversibility, and cell
      type specificity of transformation by oncogenic C-RAF. Targeting expression to
      alveolar type II cells or to Clara cells, the two likely precursors of human
      NSCLC, revealed differential tumorigenicity between these cells. Whereas
      expression of oncogenic C-RAF in alveolar type II cells readily induced
      multifocal macroscopic lung tumors independent of the developmental state, few
      tumors with type II pneumocytes features and incomplete penetrance were found
      when targeted to Clara cells. Induced tumors did not progress and were strictly
      dependent on the initiating oncogene. Deinduction of mice resulted in tumor
      regression due to autophagy rather than apoptosis. Induction of autophagic cell
      death in regressing lung tumors suggests the use of autophagy enhancers as a
      treatment choice for patients with NSCLC.

PMID- 22131877
TI  - Detection of somatic copy number alterations in cancer using targeted exome
      capture sequencing.
AB  - The research community at large is expending considerable resources to sequence
      the coding region of the genomes of tumors and other human diseases using
      targeted exome capture (i.e., "whole exome sequencing"). The primary goal of
      targeted exome sequencing is to identify nonsynonymous mutations that potentially
      have functional consequences. Here, we demonstrate that whole-exome sequencing
      data can also be analyzed for comprehensively monitoring somatic copy number
      alterations (CNAs) by benchmarking the technique against conventional array CGH.
      A series of 17 matched tumor and normal tissues from patients with metastatic
      castrate-resistant prostate cancer was used for this assessment. We show that
      targeted exome sequencing reliably identifies CNAs that are common in advanced
      prostate cancer, such as androgen receptor (AR) gain and PTEN loss. Taken
      together, these data suggest that targeted exome sequencing data can be
      effectively leveraged for the detection of somatic CNAs in cancer.

PMID- 22131878
TI  - Disclosure of erlotinib as a multikinase inhibitor in pancreatic ductal
      adenocarcinoma.
AB  - A placebo-controlled phase 3 trial demonstrated that the epidermal growth factor
      receptor (EGFR) inhibitor erlotinib in combination with gemcitabine was
      especially efficient in a pancreatic ductal adenocarcinoma (PDAC) subgroup of
      patients developing skin toxicity. However, EGFR expression was not predictive
      for response, and markers to characterize an erlotinib-responding PDAC group are
      currently missing. In this work, we observed high erlotinib IC50 values in a
      panel of human and murine PDAC cell lines. Using EGFR small interfering RNA, we
      detected that the erlotinib response was marginally influenced by EGFR. To find
      novel EGFR targets, we used an unbiased chemical proteomics approach for target
      identification and quality-controlled target affinity determination combined with
      quantitative mass spectrometry based on stable isotope labeling by amino acids in
      cell culture. In contrast to gefitinib, we observed a broad target profile of
      erlotinib in PDAC cells by quantitative proteomics. Six protein kinases bind to
      erlotinib with similar or higher affinity (K(d) = 0.09-0.358 uM) than the EGFR
      (K(d) 0.434 uM). We provide evidence that one of the novel erlotinib targets,
      ARG, contributes in part to the erlotinib response in a PDAC cell line. Our data
      show that erlotinib is a multikinase inhibitor, which can act independent of EGFR
      in PDAC. These findings may help to monitor future erlotinib trials in the
      clinic.

PMID- 22131879
TI  - A high occurrence of acquisition and/or expansion of C-CBL mutant clones in the
      progression of high-risk myelodysplastic syndrome to acute myeloid leukemia.
AB  - The molecular pathogenesis of myelodysplastic syndrome (MDS) and its progression
      to secondary acute myeloid leukemia (sAML) remain to be explored. Somatic C-CBL
      mutations were recently described in MDS. Our study aimed to determine the role
      of C-CBL mutations in the progression of MDS to sAML and sought to correlate with
      clinicohematological features and outcome. Bone marrow samples from 51 patients
      with high-risk MDS (13 with refractory cytopenia with multilineage dysplasia, 19
      with refractory anemia with excess blast 1, and 19 with refractory anemia with
      excess blast 2) were analyzed for C-CBL mutations at both diagnosis and sAML in
      the same individuals. Mutational analysis was performed for exons 7 to 9 of C-CBL
      gene. Of the 51 paired samples, C-CBL mutations were identified in 6 patients at
      the sAML phase. One patient retained the identical C-CBL mutation (G415S) at sAML
      evolution and exhibited clonal expansion. The other five patients acquired C-CBL
      mutations (Y371S, F418S, L370_Y371 ins L, L399V, and C416W) during sAML
      evolution. Three of the six patients harboring C-CBL mutations at sAML had
      additional gene mutations including JAK2(V617F), PTPN11, or N-RAS. There was no
      significant difference in clinicohematological features and overall survival with
      respect to C-CBL mutation status. Our results show that C-CBL mutation is very
      rare (0.6%) in MDS, but acquisition and/or expansion of C-CBL mutant clones occur
      in 11.8% of patients during sAML transformation. The findings suggest that C-CBL
      mutations play a role at least in part in a subset of MDS patients during sAML
      transformation.

PMID- 22131880
TI  - A novel topoisomerase inhibitor, daurinol, suppresses growth of HCT116 cells with
      low hematological toxicity compared to etoposide.
AB  - We report that daurinol, a novel arylnaphthalene lignan, is a promising potential
      anticancer agent with adverse effects that are less severe than those of
      etoposide, a clinical anticancer agent. Despite its potent antitumor activity,
      clinical use of etoposide is limited because of its adverse effects, including
      myelosuppression and the development of secondary leukemia. Here, we
      comprehensively compared the mechanistic differences between daurinol and
      etoposide because they have similar chemical structures. Etoposide, a
      topoisomerase II poison, is known to attenuate cancer cell proliferation through
      the inhibition of DNA synthesis. Etoposide treatment induces G(2)/M arrest,
      severe DNA damage, and the formation of giant nuclei in HCT116 cells. We
      hypothesized that the induction of DNA damage and nuclear enlargement due to
      abnormal chromosomal conditions could give rise to genomic instability in both
      tumor cells and in actively dividing normal cells, resulting in the toxic adverse
      effects of etoposide. We found that daurinol is a catalytic inhibitor of human
      topoisomerase IIa, and it induces S-phase arrest through the enhanced expression
      of cyclins E and A and by activation of the ATM/Chk/Cdc25A pathway in HCT116
      cells. However, daurinol treatment did not cause DNA damage or nuclear
      enlargement in vitro. Finally, we confirmed the in vivo antitumor effects and
      adverse effects of daurinol and etoposide in nude mice xenograft models. Daurinol
      displayed potent antitumor effects without any significant loss of body weight or
      changes in hematological parameters, whereas etoposide treatment led to decreased
      body weight and white blood cell, red blood cell, and hemoglobin concentration.

PMID- 22131881
TI  - The Jak2 inhibitor, G6, alleviates Jak2-V617F-mediated myeloproliferative
      neoplasia by providing significant therapeutic efficacy to the bone marrow.
AB  - We recently developed a Janus kinase 2 (Jak2) small-molecule inhibitor called G6
      and found that it inhibits Jak2-V617F-mediated pathologic cell growth in vitro,
      ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F-mediated
      myeloproliferative neoplasia, with particular emphasis in the bone marrow, has
      not previously been examined. Here, we investigated the efficacy of G6 in a
      transgenic mouse model of Jak2-V617F-mediated myeloproliferative neoplasia. We
      found that G6 provided therapeutic benefit to the peripheral blood as determined
      by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized
      the pathologically high plasma concentrations of interleukin 6 (IL-6). In the
      liver, G6 eliminated Jak2-V617F-driven extramedullary hematopoiesis. With respect
      to the spleen, G6 significantly reduced both the splenomegaly and megakaryocytic
      hyperplasia. In the critically important bone marrow, G6 normalized the
      pathologically high levels of phospho-Jak2 and phospho-signal transducer and
      activator of transcription 5 (STAT5). It significantly reduced the megakaryocytic
      hyperplasia in the marrow and completely normalized the M/E ratio. Most
      importantly, G6 selectively reduced the mutant Jak2 burden by 67%on average, with
      virtual elimination of mutant Jak2 cells in one third of all treated mice.
      Lastly, clonogenic assays using marrow stem cells from the myeloproliferative
      neoplasm mice revealed a time-dependent elimination of the clonogenic growth
      potential of these cells by G6. Collectively, these data indicate that G6
      exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most
      importantly, in the bone marrow, thereby raising the possibility that this
      compound may alter the natural history of Jak2-V617F-mediated myeloproliferative
      neoplasia.

PMID- 22131883
TI  - Activation of the long terminal repeat of human endogenous retrovirus K by
      melanoma-specific transcription factor MITF-M.
AB  - The human and Old World primate genomes possess conserved endogenous retrovirus
      sequences that have been implicated in evolution, reproduction, and
      carcinogenesis. Human endogenous retrovirus (HERV)-K with 5'LTR-gag-pro-pol-env
      rec/np9-3'LTR sequences represents the newest retrovirus family that integrated
      into the human genome 1 to 5 million years ago. Although a high-level expression
      of HERV-K in melanomas, breast cancers, and teratocarcinomas has been
      demonstrated, the mechanism of the lineage-specific activation of the long
      terminal repeat (LTR) remains obscure. We studied chromosomal HERV-K expression
      in MeWo melanoma cells in comparison with the basal expression in human embryonic
      kidney 293 (HEK293) cells. Cloned LTR of HERV-K (HML-2.HOM) was also
      characterized by mutation and transactivation experiments. We detected multiple
      transcriptional initiator (Inr) sites in the LTR by rapid amplification of
      complementary DNA ends (5' RACE). HEK293 and MeWo showed different Inr usage. The
      most potent Inr was associated with a TATA box and three binding motifs of
      microphthalmia-associated transcription factor (MITF). Both chromosomal HERV-K
      expression and the cloned LTR function were strongly activated in HEK293 by
      transfection with MITF-M, a melanocyte/melanoma-specific isoform of MITF.
      Coexpression of MITF and the HERV-K core antigen was detected in retinal
      pigmented epithelium by an immunofluorescence analysis. Although malignant
      melanoma lines MeWo, G361, and SK-MEL-28 showed enhanced HERV-K transcription
      compared with normal melanocytes, the level of MITF-M messenger RNA persisted
      from normal to transformed melanocytes. Thus, MITF-M may be a prerequisite for
      the pigmented cell lineage-specific function of HERV-K LTR, leading to the high
      level expression in malignant melanomas.

PMID- 22131882
TI  - DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired
      platinum resistance.
AB  - Clinical resistance to chemotherapy is a frequent event in cancer treatment and
      is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is
      characterized by p53 mutation and high levels of genomic instability. Treatment
      includes platinum-based chemotherapy and initial response rates are high;
      however, resistance is frequently acquired, at which point treatment options are
      largely palliative. Recent data indicate that platinum-resistant clones exist
      within the sensitive primary tumor at presentation, implying resistant cell
      selection after treatment with platinum chemotherapy. The AKT pathway is central
      to cell survival and has been implicated in platinum resistance. Here, we show
      that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response
      in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates
      to the nucleus of resistant cells where it is phosphorylated specifically on S473
      by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin
      mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores
      platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell
      lines: we also demonstrate these effects in other tumor types. Resensitization is
      associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in
      patient-matched sensitive cells, we do not see enhanced apoptosis on combining
      cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is
      unaffected by DNA-PK inhibitor treatment, suggesting that this effect is
      restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK
      inhibition might prevent platinum-induced AKT activation without interfering with
      normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors.

PMID- 22131884
TI  - Modeling pharmacological inhibition of mast cell degranulation as a therapy for
      insulinoma.
AB  - Myc, a pleiotropic transcription factor that is deregulated and/or overexpressed
      in most human cancers, instructs multiple extracellular programs that are
      required to sustain the complex microenvironment needed for tumor maintenance,
      including remodeling of tumor stroma, angiogenesis, and inflammation. We
      previously showed in a model of pancreatic beta-cell tumorigenesis that acute Myc
      activation in vivo triggers rapid recruitment of mast cells to the tumor site and
      that this is absolutely required for angiogenesis and macroscopic tumor
      expansion. Moreover, systemic inhibition of mast cell degranulation with sodium
      cromoglycate induced death of tumor and endothelial cells in established tumors.
      Hence, mast cells are required both to establish and to maintain the tumors.
      Whereas this intimates that selective inhibition of mast cell function could be
      therapeutically efficacious, cromoglycate is not a practical drug for systemic
      delivery in humans, and no other systemic inhibitor of mast cell degranulation
      has hitherto been available. PCI-32765 is a novel inhibitor of Bruton tyrosine
      kinase (Btk) that blocks mast cell degranulation and is currently in clinical
      trial as a therapy for B-cell non-Hodgkin lymphoma. Here, we show that systemic
      treatment of insulinoma-bearing mice with PCI-32765 efficiently inhibits Btk,
      blocks mast cell degranulation, and triggers collapse of tumor vasculature and
      tumor regression. These data reinforce the notion that mast cell function is
      required for maintenance of certain tumor types and indicate that the Btk
      inhibitor PCI-32765 may be useful in treating such diseases.

PMID- 22131886
TI  - LogViewer: a software tool to visualize quality control parameters to optimize
      proteomics experiments using Orbitrap and LTQ-FT mass spectrometers.
AB  - Visualization tools that allow both optimization of instrument's parameters for
      data acquisition and specific quality control (QC) for a given sample prior to
      time-consuming database searches have been scarce until recently and are
      currently still not freely available. To address this need, we have developed the
      visualization tool LogViewer, which uses diagnostic data from the RAW files of
      the Thermo Orbitrap and linear trap quadrupole-Fourier transform (LTQ-FT) mass
      spectrometers to monitor relevant metrics. To summarize and visualize the
      performance on our test samples, log files from RawXtract are imported and
      displayed. LogViewer is a visualization tool that allows a specific and fast QC
      for a given sample without time-consuming database searches. QC metrics displayed
      include: mass spectrometry (MS) ion-injection time histograms, MS ion-injection
      time versus retention time, MS(2) ion-injection time histograms, MS(2) ion
      injection time versus retention time, dependent scan histograms, charge-state
      histograms, mass-to-charge ratio (M/Z) distributions, M/Z histograms, mass
      histograms, mass distribution, summary, repeat analyses, Raw MS, and Raw MS(2).
      Systematically optimizing all metrics allowed us to increase our protein
      identification rates from 600 proteins to routinely determine up to 1400 proteins
      in any 160-min analysis of a complex mixture (e.g., yeast lysate) at a false
      discovery rate of <1%. Visualization tools, such as LogViewer, make QC of complex
      liquid chromotography (LC)-MS and LC-MS/MS data and optimization of the
      instrument's parameters accessible to users.

PMID- 22131887
TI  - Institutional management of core facilities during challenging financial times.
AB  - The economic downturn is likely to have lasting effects on institutions of higher
      education, prioritizing proactive institutional leadership and planning. Although
      by design, core research facilities are more efficient and effective than
      supporting individual pieces of research equipment, cores can have significant
      underlying financial requirements and challenges. This paper explores several
      possible institutional approaches to managing core facilities during challenging
      financial times.

PMID- 22131888
TI  - University multi-user facility survey-2010.
AB  - Multi-user facilities serve as a resource for many universities. In 2010, a
      survey was conducted investigating possible changes and successful
      characteristics of multi-user facilities, as well as identifying problems in
      facilities. Over 300 surveys were e-mailed to persons identified from university
      websites as being involved with multi-user facilities. Complete responses were
      received from 36 facilities with an average of 20 years of operation. Facilities
      were associated with specific departments (22%), colleges (22%), and university
      research centers (8.3%) or were not affiliated with any department or college
      within the university (47%). The five most important factors to succeed as a
      multi-user facility were: 1) maintaining an experienced, professional staff in an
      open atmosphere; 2) university-level support providing partial funding; 3) broad
      client base; 4) instrument training programs; and 5) an effective leader and
      engaged strategic advisory group. The most significant problems were: 1)
      inadequate university financial support and commitment; 2) problems recovering
      full service costs from university subsidies and user fees; 3) availability of
      funds to repair and upgrade equipment; 4) inability to retain highly qualified
      staff; and 5) unqualified users dirtying/damaging equipment. Further information
      related to these issues and to fee structure was solicited. Overall, there
      appeared to be a decline in university support for facilities and more emphasis
      on securing income by serving clients outside of the institution and by obtaining
      grants from entities outside of the university.

PMID- 22131891
TI  - Feza h. Remzi, M.D.

PMID- 22131889
TI  - Uromodulin exclusion list improves urinary exosomal protein identification.
AB  - Advances in mass spectrometry (MS) have encouraged interest in its deployment in
      urine biomarker studies, but success has been limited. Urine exosomes have been
      proposed as an ideal source of biomarkers for renal disease. However, the
      abundant urinary protein, uromodulin, cofractionates with exosomes during
      isolation and represents a practical contaminant that limits MS sensitivity.
      Uromodulin depletion has been attempted but is labor- and time-intensive and may
      remove important protein biomarkers. We describe the application of an exclusion
      list (ExL) of uromodulin-related peptide ions, coupled with high-sensitivity mass
      spectrometric analysis, to increase the depth of coverage of the urinary exosomal
      proteome. Urine exosomal protein samples from healthy volunteers were subjected
      to tandem MS and abundant uromodulin peptides identified. Samples were run for a
      second time, while excluding these uromodulin peptides from fragmentation to
      allow identification of peptides from lower-abundance proteins. Uromodulin
      exclusion was performed in addition to dynamic exclusion. Results from these two
      procedures revealed 222 distinct proteins from conventional analysis, compared
      with 254 proteins after uromodulin exclusion, of which 188 were common to both
      methods. By unmasking a previously unidentified protein set, adding the ExL
      increased overall protein identifications by 29.7% to a total of 288 proteins. A
      fixed ExL, used in combination with conventional methods, effectively increases
      the depth of urinary exosomal proteins identified by MS, reducing the need for
      uromodulin depletion.

PMID- 22131892
TI  - Ulcerative colitis.

PMID- 22131894
TI  - Technical aspects of ileoanal pouch surgery in patients with ulcerative colitis.
AB  - Restorative proctocolectomy with ileal pouch-anal anastomosis is the procedure of
      choice for patients with ulcerative colitis requiring surgery. A J-pouch with a
      stapled anastomosis has been the preferred technique because it is quicker,
      safer, and associated with good functional outcomes. A diverting loop ileostomy
      is usually created at the time of ileal pouch-anal anastomosis. In patients with
      severe fulminant colitis or toxic megacolon, restorative proctocolectomy with
      ileal pouch-anal anastomosis is performed in multistages. The technical aspects
      of ileal pouch-anal anastomosis in patients with ulcerative colitis are reviewed
      in this article.

PMID- 22131893
TI  - Pros and cons of medical management of ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disease characterized by
      diffuse mucosal inflammation limited to the colon and rectum. Although a complete
      medical cure may not be possible, UC can be treated with medications that induce
      and maintain remission. The medical management of this disease continues to
      evolve with a goal to avoid colectomy and ultimately alter the natural history of
      UC. Emergence of antitumor necrosis factor-alpha (TNF-alpha) agents has expanded
      the medical armamentarium. 5-Aminosalicylates continue to be used in mild to
      moderate UC and corticosteroids are mainly used for induction of remission with
      immunomodulators (6-mercaptopurine/azathiopurine/methotrexate) being applied as
      steroid-sparing agents for maintenance therapy. Infliximab has been approved by
      the U.S. Food and Drug Administration and used in the treatment of moderate to
      severe UC; nevertheless, its use may be associated with significant adverse
      effects and have a negative impact on the postoperative course should the
      patients undergo restorative proctocolectomy. In addition, there is always a
      concern about patients' compliance to medical therapy, cost of medications, and
      risk for UC-associated dysplasia. The authors discuss the pros and cons of
      medications used in the treatment of UC.

PMID- 22131895
TI  - Laparoscopic surgery for ulcerative colitis.
AB  - Laparoscopic techniques have become increasingly used in the treatment of
      ulcerative colitis: in experienced hands, they are safe and feasible. Recovery
      advantages have not been consistently demonstrated and functional results have
      been comparable to open surgery. Other possible benefits and costs issues have
      also been inconsistent. Further investigation on the role of laparoscopic surgery
      for ulcerative colitis with larger populations and longer follow-up with a focus
      on recovery parameters, quality of life, and costs are needed.

PMID- 22131897
TI  - Ileorectal anastomosis and proctocolectomy with end ileostomy for ulcerative
      colitis.
AB  - Until the development of the ileal pouch-anal anastomosis in the early 1980s,
      proctocolectomy with end ileostomy was the only definitive surgery for ulcerative
      colitis and colectomy with ileorectal anastomosis was the procedure of choice for
      affected patients who were reluctant to have a permanent ileostomy. Currently,
      ileal pouch-anal anastomosis is the most common procedure for patients with
      ulcerative colitis requiring surgical treatment. However, there is still a role
      for ileorectal anastomosis and proctocolectomy with end ileostomy for a selected
      group of patients. In this review, the authors summarize the current indications
      for ileorectal anastomosis and proctocolectomy with end ileostomy in patients
      with ulcerative colitis.

PMID- 22131896
TI  - Diagnosis and management of postoperative ileal pouch disorders.
AB  - Although restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has
      become the surgical treatment of choice for patients with refractory ulcerative
      colitis (UC) or UC with dysplasia, surgical, inflammatory, and noninflammatory
      adverse sequelae are common. Pouchitis, representing a spectrum of disease
      phenotypes, is the most common long-term complication of IPAA. De novo Crohn
      disease (CD) of the pouch can occur in patients with a preoperative diagnosis of
      UC. Differential diagnosis between fibrostenotic or fistulizing CD and surgery
      associated strictures, sinuses, and fistulas often requires a combined assessment
      of symptom, endoscopy, histology, radiography, and examination under anesthesia.
      There is a role for endoscopic therapy for stricturing complications of IPAA.
      Chronic antibiotic-refractory pouchitis, refractory cuffitis, as well as
      fibrostenotic or fistulizing CD of the pouch are the leading late-onset causes
      for pouch failure.

PMID- 22131898
TI  - Management of acute colitis and toxic megacolon.
AB  - Severe colitis is a well-defined condition that can develop in patients afflicted
      with ulcerative colitis, but typically responds to a variety of medical
      therapies. Operative intervention is warranted when massive hemorrhage,
      perforation, or peritonitis complicates the clinical scenario or medical therapy
      fails to control the disease. Of the operative options, total/subtotal colectomy
      and end ileostomy is the usual procedure of choice especially if the operation
      can be performed through a laparoscopic approach.

PMID- 22131899
TI  - A swell in the armamentarium of antiepileptic drug targets.
AB  - Although long granted the status of immune privilege, the central nervous system
      is not completely isolated from the immune system. Increasing evidence suggests
      that this system contributes to seizures and epilepsy and that the molecular
      mediators of inflammation and immunity may serve as appropriate targets in the
      quest to develop novel antiepileptic drugs that are more efficacious and
      potentially disease modifying.

PMID- 22131900
TI  - Is it safe to use a diuretic to treat seizures early in development ?
AB  - There has been considerable interest in using bumetanide, a diuretic chloride
      importer NKCC1 antagonist, to reduce intracellular chloride ([Cl(-)](i)) in
      epileptic neurons, thereby shifting the polarity of GABA from excitatory to
      inhibitory and ameliorating the actions of GABA-acting antiepileptic drugs.
      However, a recent study raises the important issue of potential deleterious
      actions of bumetanide on immature neurons, because reduction of (Cl(-))(i) also
      alleviates a major source of excitation in developing neurons, upon which GABA
      exerts a trophic action. This review considers the importance of separating
      intrauterine from postnatal effects of bumetanide in normal versus pathologic
      neurons.

PMID- 22131901
TI  - Current Antiviral Therapy of Chronic Hepatitis B: Efficacy and Safety.
AB  - The treatment of chronic hepatitis B is in constant evolution. Interferon, the
      first agent licensed for chronic hepatitis B treatment, has been superseded by
      the growing popularity of nucleoside/nucleotide analogues (NA). However,
      resistance to these agents is a major challenge. Newer NAs, such as entecavir and
      tenofovir dipivoxil fumarate, have very low resistance rates and favorable safety
      profiles. Long-term use of these agents can effectively suppress hepatitis B
      virus DNA, leading to decrease in incidence of hepatitic flares, as well as in
      the development of cirrhosis and hepatocellular carcinoma. The efficacy and
      safety of various antiviral agents is discussed in this review.

PMID- 22131902
TI  - Deficient induction response in a Xenopus nucleocytoplasmic hybrid.
AB  - Incompatibilities between the nucleus and the cytoplasm of sufficiently distant
      species result in developmental arrest of hybrid and nucleocytoplasmic hybrid
      (cybrid) embryos. Several hypotheses have been proposed to explain their
      lethality, including problems in embryonic genome activation (EGA) and/or nucleo
      mitochondrial interactions. However, conclusive identification of the causes
      underlying developmental defects of cybrid embryos is still lacking. We show here
      that while over 80% of both Xenopus laevis and Xenopus (Silurana) tropicalis same
      species androgenetic haploids develop to the swimming tadpole stage, the
      androgenetic cybrids formed by the combination of X. laevis egg cytoplasm and X.
      tropicalis sperm nucleus invariably fail to gastrulate properly and never reach
      the swimming tadpole stage. In spite of this arrest, these cybrids show
      quantitatively normal EGA and energy levels at the stage where their initial
      gastrulation defects are manifested. The nucleocytoplasmic incompatibility
      between these two species instead results from a combination of factors,
      including a reduced emission of induction signal from the vegetal half, a
      decreased sensitivity of animal cells to induction signals, and differences in a
      key embryonic protein (Xbra) concentration between the two species, together
      leading to inefficient induction and defective convergence-extension during
      gastrulation. Indeed, increased exposure to induction signals and/or Xbra
      signalling partially rescues the induction response in animal explants and whole
      cybrid embryos. Altogether, our study demonstrates that the egg cytoplasm of one
      species may not support the development promoted by the nucleus of another
      species, even if this nucleus does not interfere with the cytoplasmic/maternal
      functions of the egg, while the egg cytoplasm is also capable of activating the
      genome of that nucleus. Instead, our results provide evidence that inefficient
      signalling and differences in the concentrations of key proteins between species
      lead to developmental defects in cybrids. Finally, they show that the
      incompatibilities of cybrids can be corrected by appropriate treatments.

PMID- 22131903
TI  - Coordinated regulation of niche and stem cell precursors by hormonal signaling.
AB  - Stem cells and their niches constitute units that act cooperatively to achieve
      adult body homeostasis. How such units form and whether stem cell and niche
      precursors might be coordinated already during organogenesis are unknown. In
      fruit flies, primordial germ cells (PGCs), the precursors of germ line stem cells
      (GSCs), and somatic niche precursors develop within the larval ovary. Together
      they form the 16-20 GSC units of the adult ovary. We show that ecdysone receptors
      are required to coordinate the development of niche and GSC precursors. At early
      third instar, ecdysone receptors repress precocious differentiation of both
      niches and PGCs. Early repression is required for correct morphogenesis of the
      ovary and for protecting future GSCs from differentiation. At mid-third instar,
      ecdysone signaling is required for niche formation. Finally, and concurrent with
      the initiation of wandering behavior, ecdysone signaling initiates PGC
      differentiation by allowing the expression of the differentiation gene bag of
      marbles in PGCs that are not protected by the newly formed niches. All the
      ovarian functions of ecdysone receptors are mediated through early repression,
      and late activation, of the ecdysone target gene broad. These results show that,
      similar to mammals, a brain-gland-gonad axis controls the initiation of oogenesis
      in insects. They further exemplify how a physiological cue coordinates the
      formation of a stem cell unit within an organ: it is required for niche
      establishment and to ensure that precursor cells to adult stem cells remain
      undifferentiated until the niches can accommodate them. Similar principles might
      govern the formation of additional stem cell units during organogenesis.

PMID- 22131905
TI  - People gather only the information they need to make decisions.

PMID- 22131904
TI  - How awareness changes the relative weights of evidence during human decision
      making.
AB  - Human decisions are based on accumulating evidence over time for different
      options. Here we ask a simple question: How is the accumulation of evidence
      affected by the level of awareness of the information? We examined the influence
      of awareness on decision-making using combined behavioral methods and magneto
      encephalography (MEG). Participants were required to make decisions by
      accumulating evidence over a series of visually presented arrow stimuli whose
      visibility was modulated by masking. Behavioral results showed that participants
      could accumulate evidence under both high and low visibility. However, a top-down
      strategic modulation of the flow of incoming evidence was only present for
      stimuli with high visibility: once enough evidence had been accrued, participants
      strategically reduced the impact of new incoming stimuli. Also, decision-making
      speed and confidence were strongly modulated by the strength of the evidence for
      high-visible but not low-visible evidence, even though direct priming effects
      were identical for both types of stimuli. Neural recordings revealed that, while
      initial perceptual processing was independent of visibility, there was stronger
      top-down amplification for stimuli with high visibility than low visibility.
      Furthermore, neural markers of evidence accumulation over occipito-parietal
      cortex showed a strategic bias only for highly visible sensory information,
      speeding up processing and reducing neural computations related to the decision
      process. Our results indicate that the level of awareness of information changes
      decision-making: while accumulation of evidence already exists under low
      visibility conditions, high visibility allows evidence to be accumulated up to a
      higher level, leading to important strategical top-down changes in decision
      making. Our results therefore suggest a potential role of awareness in deploying
      flexible strategies for biasing information acquisition in line with one's
      expectations and goals.

PMID- 22131906
TI  - Survival of the synesthesia gene: why do people hear colors and taste words?
AB  - Synesthesia is a perceptual experience in which stimuli presented through one
      modality will spontaneously evoke sensations in an unrelated modality. The
      condition occurs from increased communication between sensory regions and is
      involuntary, automatic, and stable over time. While synesthesia can occur in
      response to drugs, sensory deprivation, or brain damage, research has largely
      focused on heritable variants comprising roughly 4% of the general population.
      Genetic research on synesthesia suggests the phenomenon is heterogeneous and
      polygenetic, yet it remains unclear whether synesthesia ever provided a selective
      advantage or is merely a byproduct of some other useful selected trait. Progress
      in uncovering the genetic basis of synesthesia will help us understand why
      synesthesia has been conserved in the population.

PMID- 22131907
TI  - HIV, gender, race, sexual orientation, and sex work: a qualitative study of
      intersectional stigma experienced by HIV-positive women in Ontario, Canada.
AB  - BACKGROUND: HIV infection rates are increasing among marginalized women in
      Ontario, Canada. HIV-related stigma, a principal factor contributing to the
      global HIV epidemic, interacts with structural inequities such as racism, sexism,
      and homophobia. The study objective was to explore experiences of stigma and
      coping strategies among HIV-positive women in Ontario, Canada. METHODS AND
      FINDINGS: We conducted a community-based qualitative investigation using focus
      groups to understand experiences of stigma and discrimination and coping methods
      among HIV-positive women from marginalized communities. We conducted 15 focus
      groups with HIV-positive women in five cities across Ontario, Canada. Data were
      analyzed using thematic analysis to enhance understanding of the lived
      experiences of diverse HIV-positive women. Focus group participants (n = 104;
      mean age = 38 years; 69% ethnic minority; 23% lesbian/bisexual; 22% transgender)
      described stigma/discrimination and coping across micro (intra/interpersonal),
      meso (social/community), and macro (organizational/political) realms.
      Participants across focus groups attributed experiences of stigma and
      discrimination to: HIV-related stigma, sexism and gender discrimination, racism,
      homophobia and transphobia, and involvement in sex work. Coping strategies
      included resilience (micro), social networks and support groups (meso), and
      challenging stigma (macro). CONCLUSIONS: HIV-positive women described
      interdependent and mutually constitutive relationships between marginalized
      social identities and inequities such as HIV-related stigma, sexism, racism, and
      homo/transphobia. These overlapping, multilevel forms of stigma and
      discrimination are representative of an intersectional model of stigma and
      discrimination. The present findings also suggest that micro, meso, and macro
      level factors simultaneously present barriers to health and well being--as well
      as opportunities for coping--in HIV-positive women's lives. Understanding the
      deleterious effects of stigma and discrimination on HIV risk, mental health, and
      access to care among HIV-positive women can inform health care provision, stigma
      reduction interventions, and public health policy.

PMID- 22131909
TI  - Responsible governance for mental health research in low resource countries.

PMID- 22131908
TI  - Effect of supplementation with zinc and other micronutrients on malaria in
      Tanzanian children: a randomised trial.
AB  - BACKGROUND: It is uncertain to what extent oral supplementation with zinc can
      reduce episodes of malaria in endemic areas. Protection may depend on other
      nutrients. We measured the effect of supplementation with zinc and other
      nutrients on malaria rates. METHODS AND FINDINGS: In a 2*2 factorial trial, 612
      rural Tanzanian children aged 6-60 months in an area with intense malaria
      transmission and with height-for-age z-score<=-1.5 SD were randomized to receive
      daily oral supplementation with either zinc alone (10 mg), multi-nutrients
      without zinc, multi-nutrients with zinc, or placebo. Intervention group was
      indicated by colour code, but neither participants, researchers, nor field staff
      knew who received what intervention. Those with Plasmodium infection at baseline
      were treated with artemether-lumefantrine. The primary outcome, an episode of
      malaria, was assessed among children reported sick at a primary care clinic, and
      pre-defined as current Plasmodium infection with an inflammatory response, shown
      by axillary temperature >=37.5 degrees C or whole blood C-reactive protein
      concentration >= 8 mg/L. Nutritional indicators were assessed at baseline and at
      251 days (median; 95% reference range: 191-296 days). In the primary intention-to
      treat analysis, we adjusted for pre-specified baseline factors, using Cox
      regression models that accounted for multiple episodes per child. 592 children
      completed the study. The primary analysis included 1,572 malaria episodes during
      526 child-years of observation (median follow-up: 331 days). Malaria incidence in
      groups receiving zinc, multi-nutrients without zinc, multi-nutrients with zinc
      and placebo was 2.89/child-year, 2.95/child-year, 3.26/child-year, and 2.87/child
      year, respectively. There was no evidence that multi-nutrients influenced the
      effect of zinc (or vice versa). Neither zinc nor multi-nutrients influenced
      malaria rates (marginal analysis; adjusted HR, 95% CI: 1.04, 0.93-1.18 and 1.10,
      0.97-1.24 respectively). The prevalence of zinc deficiency (plasma zinc
      concentration <9.9 umol/L) was high at baseline (67% overall; 60% in those
      without inflammation) and strongly reduced by zinc supplementation. CONCLUSIONS:
      We found no evidence from this trial that zinc supplementation protected against
      malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00623857

PMID- 22131910
TI  - Genome majority vote improves gene predictions.
AB  - Recent studies have noted extensive inconsistencies in gene start sites among
      orthologous genes in related microbial genomes. Here we provide the first
      documented evidence that imposing gene start consistency improves the accuracy of
      gene start-site prediction. We applied an algorithm using a genome majority vote
      (GMV) scheme to increase the consistency of gene starts among orthologs. We used
      a set of validated Escherichia coli genes as a standard to quantify accuracy.
      Results showed that the GMV algorithm can correct hundreds of gene prediction
      errors in sets of five or ten genomes while introducing few errors. Using a
      conservative calculation, we project that GMV would resolve many inconsistencies
      and errors in publicly available microbial gene maps. Our simple and logical
      solution provides a notable advance toward accurate gene maps.

PMID- 22131911
TI  - CD133, Stem Cells, and Cancer Stem Cells: Myth or Reality?
AB  - CD133, a member of the prominin family, is found in a variety of tissues with at
      least three variants. The function of CD133 is not well understood, but its
      expression is subject to changes in the microenvironment cues including
      bioenergetic stress. Knockout of CD133 does not affect renewal, but mammary gland
      branching. A point mutation of CD133 (R733C) leads to retinal disorder. CD133 is
      found in embryonic stem cells, normal tissue stem cells, stem cell niches, and
      circulating endothelial progenitors as well as cancer stem cells. Maintenance of
      stemness in cancer may be attributable to asymmetric cell division in association
      with a set of embryonic expression signatures in CD133+ tumor cells. CD133 could
      enrich cancer stem cells, which are associated with chemo- and radiation
      resistance phenotype. High CD133 is associated with poor survival in a variety of
      solid tumors, including lung, colon, prostate, etc. Monitoring CD133+ cells in
      peripheral blood, and targeting CD133 in cancer, may further predict and improve
      the clinical outcomes.

PMID- 22131912
TI  - Treatment of acute scaphoid fractures: a systematic review and meta-analysis.
AB  - BACKGROUND/METHODS: The purpose of this review was to assess the current evidence
      supporting operative fixation versus casting for acute scaphoid fractures through
      a systematic review and meta-analysis of the literature. RESULTS: Our search
      yielded 59 articles that met our inclusion criteria with five studies achieving
      high, 22 moderate, and 32 low Structured Effectiveness Quality Evaluation Scale
      scores. Pooled results of the four Sackett level 1 evidence studies showed no
      significant difference between the operative (114/115, 99%) versus non-operative
      group (106/112, 95%) (p = 0.07) when the definition of nonunion was based on more
      definitive criterion versus plain radiographs that may be insufficient to assess
      bony union. Similar results were found for the Sackett level 2 and 4 articles.
      CONCLUSIONS: This systematic review reveals that significant weaknesses exist in
      the literature with respect to the level of evidence and quality of published
      studies on this topic. Currently, there is insufficient evidence to support the
      most effective treatment for acute scaphoid fractures.

PMID- 22131913
TI  - Is there Light at the End of the Tunnel? Controversies in the Diagnosis and
      Management of Carpal Tunnel Syndrome.
AB  - Carpal tunnel syndrome is a common disorder responsible for considerable patient
      suffering and cost to health services. Despite extensive research, controversies
      still exist with regards to best practice in diagnosis, treatment, and service
      provision. Current best practise would support the use of history, examination
      and electro-diagnostic studies. The role for ultrasound scanning in diagnosis of
      carpal tunnel syndrome is yet to be proven. It appears magnetic resonance image
      scanning has a role where a rare cause for carpal tunnel syndrome may be
      suspected and also in the detailed reconstruction of the anatomy to aid
      endoscopic procedures. Treatment options can be surgical or non-surgical and
      patient choice will dictate the decision. For non-surgical interventions many
      options have been trialled but until now only steroid use, acupuncture, and
      splinting have shown discernable benefits. Open surgical decompression of the
      carpal tunnel appears to be more simple and cost-effective than minimally
      invasive interventions. For those patients who reject surgery, splinting,
      acupuncture, and steroid injection can play a role. Recent work looking at
      different service delivery options has shown some positive results in terms of
      decreasing patient waiting time for definitive treatment. However, no formal cost
      effectiveness analysis has been published and concerns exist about the impact of
      a stream-lined service on surgical training. In this review, we look at the
      different diagnostic and treatment options for managing carpal tunnel syndrome.
      We then consider the different service delivery options and finally the cost
      effectiveness evidence.

PMID- 22131914
TI  - Evaluation of sleep position as a potential cause of carpal tunnel syndrome:
      preferred sleep position on the side is associated with age and gender.
AB  - PURPOSE: To test the hypothesis that an important step in a causative mechanism
      for carpal tunnel syndrome (CTS) is sleeping in a lateral position (sleeping on
      the side), we designed a cross-sectional survey to measure the association
      between sleep position, age, gender, and body mass index (BMI). METHODS AND
      FINDINGS: We surveyed 247 patients in a primary care setting. Fifty percent of
      men and 73% of women prefer to sleep on their side (p < .001; unadjusted odds
      ratio, 2.7). In addition, the proportion of women who prefer to sleep on their
      side increased with increasing age (p < .001). There was no association between
      BMI and sleeping in a lateral position. CONCLUSIONS: This study supports the
      hypothesis that sleeping on the side is an important step in a causal pathway for
      CTS.

PMID- 22131915
TI  - Fibonacci, littler, and the hand: a brief review.
AB  - In a landmark paper published in 1973, the eminent hand surgeon J. William
      Littler, MD, proposed two mathematical relationships between the anatomic and
      functional geometry of the hand. His proposal that the motion of the tips of the
      fingers follow an equiangular spiral has been experimentally supported. Studies
      have not supported his other idea that the lengths of the phalanges follow a
      Fibonacci series. This review, after providing the necessary mathematical
      background, reexamines Littler's claims, presents the associated studies, and re
      evaluates their conclusions. Our analysis shows that the functional lengths of
      the phalanges of the little finger actually do follow a Fibonacci series and that
      the functional lengths of the index, long, and ring fingers follow a mathematical
      relative of the Fibonacci series.

PMID- 22131916
TI  - The classic reprint: Why I hate the index finger by William L. White originally
      published in Orthopaedic Review 9:23-29, 1980.
AB  - In 1980, William White published a paper "Why I Hate the Index Finger". The
      National Library of Medicine never indexed it so it has been missing for almost
      30 years. It is reprinted here for the benefit of the current generation of hand
      surgeons.

PMID- 22131917
TI  - Sensory restoration by lateral antebrachial cutaneous to ulnar nerve transfer in
      children with global brachial plexus injuries.
AB  - Selective peripheral nerve transfers represent an emerging reconstructive
      strategy in the management of both pediatric and adult brachial plexus and
      peripheral nerve injuries. Transfer of the lateral antebrachial cutaneous nerve
      of the forearm into the distal ulnar nerve is a useful means to restore
      sensibility to the ulnar side of the hand when indicated. This technique is
      particularly valuable in the management of global brachial plexus birth injuries
      in children for which its application has not been previously reported. Four
      children ages 4 to 9 years who sustained brachial plexus birth injury with
      persistent absent sensibility on the unlar aspect of the hand underwent transfer
      of the lateral antebrachial cutaneous nerve to the distal ulnar nerve. In three
      patients, a direct transfer with a distal end-to-side repair through a deep
      longitudinal neurotomy was performed. In a single patient, an interposition nerve
      graft was required. Restoration of sensibility was evaluated by the "wrinkle
      test."

PMID- 22131918
TI  - Does Radial Styloid Abnormality in de Quervain's Disease Affect the Outcome of
      Management?
AB  - Radiological changes have been described in de Quervain's disease of the wrist.
      The author analyzed the clinical data of 114 patients who reported to the
      orthopedic clinic of a Regional Referral Hospital for a period of 4 years [2003
      to 2007]. Radiographs of the wrist were available for 39 cases, of which 14
      [35.89%] were found abnormal. Two patients with abnormal radiographs [14.28%]
      required surgery where as 7 out of 25 [28%] with normal radiographs were managed
      surgically. Radial styloid abnormality was not found statistically significant [p
      < 0.05], and the outcome of management was irrespective of the changes in the
      radial styloid.

PMID- 22131919
TI  - Closed Zone III Rupture of the Flexor Digitorum Profundus Tendons of the Right
      Index, Long, and Ring Fingers in a Bowler: Gutterball Syndrome.
AB  - Zone III flexor tendon injuries are relatively rare in comparison to other flexor
      tendon injuries in zones I, II, IV, and V. Often, these are open injuries
      resulting from an electrical device like a saw; however, closed injures are even
      rarer, and those mid-substance ruptures resulting from bowling with no evidence
      of underlying tendinopathy from diseases like gout are highly unusual. The
      principles underlying tendon repair remain the same regardless of the etiology.
      In this case, we delineate some of the options and stress the guiding principles
      of the various methods available in this interesting and unusual case.

PMID- 22131920
TI  - Cutaneous nerves at risk during the posterior midline approach to the elbow.
AB  - The purpose of this study was to investigate the cutaneous nerves at risk during
      the posterior midline approach to the elbow and proximal ulna. Ten fresh frozen
      cadaver upper extremities were used for this study. A posterior midline skin
      incision extending from 10 cm proximal to 15 cm distal to the olecranon tip was
      created. All superficial nerves were identified and preserved. Nerve diameters
      were measured, their distance from the olecranon tip assessed, and they were
      dissected proximally to confirm their nerve of origin. Point of nerve
      arborization to skin from the midline incision was quantified. An average of one
      confirmed nerve proximal and five distal to the olecranon tip were identified
      with an average diameter of 0.9 mm proximal and 1.3 mm distal to the olecranon.
      The largest nerves were typically located 2 cm proximal (range 7-46 mm) and 45 mm
      distal (range 9-135 mm) to the olecranon. The branches arborized into the skin an
      average of 5.2 mm lateral to the incision. All nerves joined the posterior medial
      antebrachial cutaneous nerve. The branches of the medial antebrachial cutaneous
      nerve are at risk with a straight posterior midline elbow incision, though the
      clinical significance of injury to these nerves at this location is unknown.

PMID- 22131922
TI  - Posterior interosseous artery flap for resurfacing posttraumatic soft tissue
      defects of the hand.
AB  - The need for soft tissue coverage of large defects in the hand and the wrist
      following trauma is a common problem for hand surgeons. Flap coverage of these
      defects can be either in the form of distant or regional flaps. The posterior
      interosseous artery flap recently has emerged as a front runner in these
      situations by its virtue to preserve both the major arteries to the hand. Thirty
      two posterior interosseous artery flaps were used in 32 patients with complex
      soft tissue defects of the hand. All these defects were posttraumatic. There were
      associated skeletal and soft tissue injuries in 20 patients. The donor site was
      closed either primarily or by a split skin graft depending on the size of the
      defect. All flaps healed well, and there were no incidences of flap necrosis. The
      donor site required a split skin graft in 24 patients. The flap was bulky in one
      patient and transient extensor carpi ulnaris weakness was seen in three patients.
      The posterior interosseous artery flap is a versatile flap for coverage of soft
      tissue defects of the hand. Good aesthetic results can be achieved with minimal
      donor site morbidity. Harvesting the flap requires a precise surgical technique
      and as many perforators as possible should be preserved to ensure flap viability.

PMID- 22131921
TI  - Bone discrepancy as a powerful indicator for early surgery in obstetric brachial
      plexus palsy.
AB  - OBJECTIVES: One of the unfortunate sequelae in obstetric brachial plexus palsy
      (OBPP) is upper limb length discrepancy. However, the influence of primary nerve
      reconstruction remains undetermined. In this study, the resultant discrepancy in
      children with OBPP who underwent primary reconstruction was analyzed in relation
      to the severity of the lesion, the timing of surgery, and the functional outcome
      following surgery. METHODS: Fifty-four patients that met the inclusion criteria
      were included in this study. Preoperative and postoperative bilateral scanograms
      were obtained to document the effect of reinnervation on bone growth. The length
      of the humerus, ulna, third metacarpal, third proximal phalange, and total limb
      length were measured and the percentage between the affected and normal side were
      accessed. Correlations between all the measures of limb length and measures of
      active motion (i.e., three different classification systems) were performed.
      RESULTS: Spearman's rank correlation coefficients revealed significant
      correlations between limb length discrepancies and nearly all measures of active
      upper extremity movement. The timing of surgery and the severity of the lesion
      significantly influenced the resultant limb length discrepancy. CONCLUSIONS: The
      prevention of a non-acceptable upper limb discrepancy is fundamental for both the
      patient and family. The extent of the resultant discrepancy appeared to be
      strongly related to the time between injury and surgery, degree of severity, and
      the outcome of surgery. Patients with better functional recoveries of the
      affected upper extremities showed smaller differences in limb length.

PMID- 22131923
TI  - A classification system for anomalies of the extensor pollicis longus.
AB  - INTRODUCTION: Variations of the long extensor tendon to the thumb are very rare.
      MATERIALS AND METHODS: We present three cases in which there was a supernumerary
      long extensor tendon to the thumb. In all three cases, the supernumerary tendon
      emerged from the fourth dorsal compartment and had a parallel course to the
      extensor pollicis longus. RESULTS: Details of the anomalies are described along
      with a meta-analysis of relevant literature. A classification system of these
      anomalies is also proposed.

PMID- 22131924
TI  - Complete annular and partial oblique pulley release for pediatric locked trigger
      thumb.
AB  - PURPOSE: To report the surgical treatment outcome of pediatric locked trigger
      thumb by sequential release of the annular pulley and partial release of the
      oblique pulley. MATERIALS AND METHODS: A retrospective review was undertaken on
      28 operative thumbs in 24 patients with an average follow-up of 79 months.
      Intraoperative observations focused on the pathology of the pulley system.
      Surgical technique involved complete release of the annular pulley, which alone
      was insufficient in relieving the deformity, along with release of the proximal
      50% of the oblique pulley in all patients. Postoperative parameters of
      bowstringing, resolution of Notta's node, thumb interphalangeal motion, and
      patient/parent satisfaction were assessed. RESULTS: The oblique pulley appeared
      stenotic, whereas the annular pulley was observed to be membranous and nearly
      indistinguishable from the tendon sheath. No patients had recurrence of thumb
      locking or triggering. No bowstringing was detected, and Notta's node resolved
      fully in 19 of 20 thumbs. Five thumbs had an average of 12(o) less active IP
      joint motion without flexion contracture (i.e., less flexion). All patients or
      families expressed overall satisfaction with the procedure. CONCLUSION: The
      annular pulley was attenuated in the majority of cases and the proximal half of
      the oblique pulley was stenotic in all patients. Releasing 50% of the oblique
      pulley after complete annular pulley release was necessary in all thumbs to
      achieve full FPL excursion. Mistaking the constricted proximal oblique pulley for
      an annular pulley may encourage releasing the entire oblique pulley, leading to
      an adverse result. Satisfactory outcome was achieved after surgical treatment of
      pediatric locked trigger thumbs. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22131925
TI  - A survey to determine current practice patterns in the surgical treatment of
      advanced thumb carpometacarpal osteoarthrosis.
AB  - BACKGROUND: The purpose of this study was to determine current practice patterns
      and examine the influence of recent evidence in the surgical treatment of
      advanced thumb carpometacarpal (CMC) osteoarthrosis. METHODS: A survey was sent
      to 2,536 American Society for Surgery of the Hand members. Information regarding
      specialty training, years of experience, annual cases performed, treatment of
      choice, technique, and postoperative immobilization was collected. Respondents
      were asked whether their current treatment of choice differs from what they
      performed 5 years ago and about the importance of ligament reconstruction and
      "interposition" to thumb CMC arthroplasty success. RESULTS: One thousand twenty
      four respondents completed the survey (40% response rate). Treatment of choice
      was trapeziectomy with ligament reconstruction and tendon interposition (68%),
      regardless of specialty training, years of experience, and annual cases
      performed. Over 70% favored treatment that was not different from what they
      performed 5 years ago. Less than 3% of respondents perform a trapeziectomy alone;
      only 14 surgeons have changed to this procedure in the last 5 years. Only 35% of
      the 822 respondents who perform a ligament reconstruction and 14% of the 764
      respondents who perform an interposition believe those techniques are "extremely
      important" to thumb CMC arthroplasty success. CONCLUSIONS: Despite recent
      evidence that suggests neither ligament reconstruction nor tendon interposition
      confers any additional benefit over trapeziectomy alone, few respondents have
      converted to the simpler procedure. Either the current evidence is not convincing
      enough to drastically change practice patterns, or other factors apart from this
      evidence have a greater influence on surgical decision-making for advanced thumb
      CMC osteoarthrosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s11552-010-9275-7) contains supplementary material, which is
      available to authorized users.

PMID- 22131926
TI  - Osteoid osteoma of the thumb: a case report.
AB  - Osteoid osteoma is a rare occurrence in the hand, and only a small percentage
      affects the thumb and distal phalanges. An 18-year-old right-hand-dominant man
      presented to our office with an approximately 1-year history of left thumb pain
      without any history of trauma. He had seen several doctors previously and
      undergone multiple diagnostic tests with no definitive diagnosis. Plain
      radiographs and computed tomography at our institution were consistent with the
      diagnosis of osteoid osteoma. The patient was treated with surgical excision of
      the lesion without bone grafting. The diagnosis of osteoid osteoma was confirmed
      by pathology. At 6 months follow-up, the patient showed complete resolution of
      pain and full restoration of hand function. This case demonstrates that osteoid
      osteoma should not be forgotten as a differential diagnosis in patients with
      finger pain, especially in individuals who have not yet or just recently have
      reached skeletal maturity.

PMID- 22131927
TI  - Endoscopic-assisted Fascial Decompression for Forearm Exertional Compartment
      Syndrome: A Case Report and Review of the Literature.
AB  - A case of chronic exertional compartment syndrome of the forearm treated with
      endoscopic-assisted fascial decompression is presented. The diagnosis of
      exertional compartment syndrome of the forearm was confirmed by direct
      measurement of intracompartmental pressures. Following endoscopic-assisted
      fascial decompression, the patient was able to begin rehabilitation therapy
      within 2 weeks. There were no wound-related complications. The patient reported
      no recurrence of symptoms after returning to work requiring heavy lifting, and
      morbidity associated with open decompression was avoided. Endoscopic release is
      not an option in traumatic compartment syndrome, but a minimally invasive
      approach may be considered in cases of exertional compartment syndrome. Reports
      of endoscopic-assisted fascial decompression in exertional compartment syndrome
      of the forearm are relatively scarce. Confirmation of the safety and efficacy of
      these evolving techniques in the hand surgery literature remains important.

PMID- 22131928
TI  - A qualitative evaluation of scaphoid remodeling in bone-grafted scaphoid
      nonunions.
AB  - The purpose of this case series is to identify and illustrate the phenomenon of
      scaphoid remodeling in skeletally mature subjects following bone grafting for
      scaphoid nonunion. Nine patients with scaphoid nonunions were treated with
      interpositional bone grafting (with iliac crest bone graft) and K-wire fixation.
      The mean length of follow-up was 28.6 +/- 9 months. Radiographs and CT scans were
      reviewed and assessed for degree of union and a qualitative assessment of
      scaphoid architecture. Following surgery, there was marked distortion of the
      scaphoid. Once healed, the contour of the scaphoid was still significantly
      distorted in all nine patients. Remodeling then became evident along the
      articular surfaces between 8 and 12 months. By 3 years, the scaphoid was
      completely recontoured and the normal architecture was completely restored in all
      nine patients. We conclude that the articular surface of the scaphoid remodels
      over time in skeletally mature subjects.

PMID- 22131929
TI  - Treatment of symptomatic distal interphalangeal joint arthritis with percutaneous
      arthrodesis: a novel technique in select patients.
AB  - Arthrodesis of the distal interphalangeal (DIP) joint is a reliable means of
      achieving pain relief in a symptomatic DIP joint afflicted by a variety of
      degenerative, inflammatory, or posttraumatic conditions. Successful arthrodesis
      is more reproducible when rigid compression of the joint is achieved. The
      emergence of an increasing number of commercially available headless or variable
      pitch compression screws reflects the growing trend among hand surgeons to
      utilize rigid stabilization of the DIP joint so that motion at more proximal
      levels can be initiated immediately without affecting arthrodesis rates.
      Successful closed percutaneous DIP arthrodesis can be achieved in a patient with
      hypertrophic osteoarthropathy, passively correctable deformity, and patients at
      increased risk for perioperative soft tissue complications associated with open
      arthrodesis. We present a novel percutaneous DIP fusion technique utilizing a
      cannulated headless compression screw in a select group of patients. The sagittal
      plane diameters of the distal and middle phalanges are templated. Cannulated
      headless compression screws, 2.4 and 3.0 mm, with short or long terminal threads
      at the leading end of the screw are selected based upon patient-specific anatomic
      considerations. Pain-free status and radiographic fusion were achieved in both
      patients (gout arthropathy, n = 1; posttraumatic arthritis, n = 1) at an average
      of 6 weeks postoperatively. Our current indications, along with pearls and
      pitfalls with this technique, are reviewed. In select patients, this percutaneous
      DIP joint arthrodesis is advantageous in comparison with open fusion techniques.

PMID- 22131930
TI  - Median Nerve Injury following K-wire Fixation of Bennett's Fracture-Lessons
      Learned.
AB  - Bennett's fracture is a relatively common injury. The fracture is unstable due to
      the displacing forces acting on the distal fragment and very commonly treated by
      stabilization with Kirschner wires. This would seem a relatively safe procedure,
      and injury to the median nerve has never been reported. We present this unusual
      complication following one such procedure with the evaluation of a safe approach
      utilizing the relevant surgical and radiological anatomy.

PMID- 22131931
TI  - Proximal carpal row dislocation: a case report.
AB  - Carpal dislocations commonly occur as the result of high-energy axial loading of
      the forearm with the wrist extended. There exists several variants of carpal
      dislocations with the most commonly observed being those about the lunate.
      Perilunate dislocations and fracture dislocations were first characterized by
      Mayfield in 1980 and represent a spectrum of traumatic carpal dislocation
      beginning radial and progressing to the ulnar side of the wrist (Mayfield et al.
      J Hand Surg [Am] 5:226-241, 1980). The path of energy takes a predictable pattern
      around the lunate from the scapho-lunate ligament, into the mid-carpal joint and
      then to the luno-triquetral joint. The final stage is volar dislocation of the
      lunate into the carpal canal. These complex fracture dislocations are unstable
      and require operative fixation through open reduction and with internal fixation
      (Herzberg et al. J Hand Surg [Am] 18:768-779, 1993; Adkison and Chapman Clin
      Orthop Rel Res 164:199-207, 1982). Other types of carpal dislocations have been
      described; however, these are much less frequently encountered (Green and O'Brien
      Clin Orthop Rel Res 149:55-72, 1980; Irwin et al. J Hand Surg [Br] 20B:746-749,
      1995; Rosado J Bone Joint Surg 48B:504-506, 1966). These also include mid-carpal
      instability and longitudinal (axial) instability and have been described
      extensively in the literature (Norbeck et al. J Hand Surg 12A:509-514, 1987;
      Primiano and Reef J Bone Joint Surg 56A:328-332, 1974; Garcia-Elias et al. J Hand
      Surg 14A:446-457, 1989; Taleisnik Hand Clinics 3:51-68, 1987). Carpal
      instabilities can be characterized as dissociative which disrupt joints within a
      carpal row, or as non-dissociative which have dislocations or subluxations
      between carpal rows (Dobyns and Cooney 1998). We report a case of complex carpal
      injury non-dissociative involving dislocation of the entire proximal carpal row
      volarly. To our knowledge such a variation of complex carpal dislocation has not
      been reported. This injury represents yet another possible variant encountered
      when treating high-energy injuries to the wrist.

PMID- 22131932
TI  - Low-grade fibromyxoid sarcoma of the hand: a case report.
AB  - We report a case of low-grade fibromyxoid sarcoma with giant collagen rosettes in
      the hand of a 21-year-old female. This is a clinically and radiological benign
      appearing tumor that has a high rate of recurrence and metastasis.

PMID- 22131933
TI  - Focal hand dystonia in a patient with ulnar nerve neuropathy at the elbow.
AB  - We describe a patient who presented with dystonia of her small finger secondary
      to entrapment neuropathy of the ulnar nerve at the elbow. Pre operative
      electrophysiological studies suggested that the locus of entrapment was located
      proximal to the medial epicondyle. This was confirmed intraoperatively by the
      presence of a thickened and prominent arcade of Struthers. Surgical decompression
      resulted in a rapid and dramatic improvement of the dystonic pattern as well as
      an improvement in nerve conduction. A review of literature has not revealed any
      other reports of such a clear cut association between ulnar nerve entrapment and
      non task-specific focal hand dystonia.

PMID- 22131934
TI  - The homodigital subcutaneous flap for soft tissue coverage of the dorsum of the
      finger: a case series.

PMID- 22131935
TI  - Why I hate the index finger.

PMID- 22131937
TI  - The dopaminergic system in peripheral blood lymphocytes: from physiology to
      pharmacology and potential applications to neuropsychiatric disorders.
AB  - Besides its action on the nervous system, dopamine (DA) plays a role on neural
      immune interactions. Here we review the current evidence on the dopaminergic
      system in human peripheral blood lymphocytes (PBL). PBL synthesize DA through the
      tyrosine-hydroxylase/DOPA-decarboxylase pathway, and express DA receptors and DA
      transporter (DAT) on their plasma membrane. Stimulation of DA receptors on PBL
      membrane contributes to modulate the development and initiation of immune
      responses under physiological conditions and in immune system pathologies such as
      autoimmunity or immunodeficiency.The characterization of DA system in PBL gave
      rise to a further line of research investigating the feasibility of PBL as a
      cellular model for studying DA derangement in neuropsychiatric disorders. Several
      reports showed changes of the expression of DAT and/or DA receptors in PBL from
      patients suffering from several neuropsychiatric disorders, in particular
      parkinsonian syndromes, schizophrenia and drug- or alcohol-abuse. Despite some
      methodological and theoretical limitations, these findings suggest that PBL may
      prove a cellular tool with which to identify the derangement of DA transmission
      in neuropsychiatric diseases, as well as to monitor the effects of
      pharmacological treatments.

PMID- 22131936
TI  - Function and pharmacology of spinally-projecting sympathetic pre-autonomic
      neurones in the paraventricular nucleus of the hypothalamus.
AB  - The paraventricular nucleus (PVN) of the hypothalamus has been described as the
      "autonomic master controller". It co-ordinates critical physiological responses
      through control of the hypothalamic-pituitary-adrenal (HPA)-axis, and by
      modulation of the sympathetic and parasympathetic branches of the central nervous
      system. The PVN comprises several anatomical subdivisions, including the
      parvocellular/ mediocellular subdivision, which contains neurones projecting to
      the medulla and spinal cord. Consensus indicates that output from spinally
      projecting sympathetic pre-autonomic neurones (SPANs) increases blood pressure
      and heart rate, and dysfunction of these neurones has been directly linked to
      elevated sympathetic activity during heart failure. The influence of spinally
      projecting SPANs on cardiovascular function high-lights their potential as
      targets for future therapeutic drug development. Recent studies have demonstrated
      pharmacological control of these spinally-projecting SPANs with glutamate, GABA,
      nitric oxide, neuroactive steroids and a number of neuropeptides (including
      angiotensin, substance P, and corticotrophin-releasing factor). The underlying
      mechanism of control appears to be a state of tonic inhibition by GABA, which is
      then strengthened or relieved by the action of other modulators. The
      physiological function of spinally-projecting SPANs has been subject to some
      debate, and they may be involved in physiological stress responses, blood volume
      regulation, glucose regulation, thermoregulation and/or circadian rhythms. This
      review describes the pharmacology of PVN spinally-projecting SPANs and discusses
      their likely roles in cardiovascular control.

PMID- 22131938
TI  - Schizophrenia: redox regulation and volume neurotransmission.
AB  - Here, we show that volume neurotransmission and the redox property of dopamine,
      as well as redox-regulated processes at glutamate receptors, can contribute
      significantly to our understanding of schizophrenia. Namely, volume
      neurotransmission may play a key role in the development of dysconnectivity
      between brain regions in schizophrenic patients, which can cause abnormal
      modulation of NMDA-dependent synaptic plasticity and produce local paroxysms in
      deafferented neural areas. During synaptic transmission, neuroredox regulations
      have fundamental functions, which involve the excellent antioxidant properties
      and nonsynaptic neurotransmission of dopamine. It is possible that the effect of
      redox-linked volume neurotransmission (diffusion) of dopamine is not as exact as
      communication by the classical synaptic mechanism, so approaching the study of
      complex schizophrenic mechanisms from this perspective may be beneficial.
      However, knowledge of redox signal processes, including the sources and molecular
      targets of reactive species, is essential for understanding the physiological and
      pathophysiological signal pathways in cells and the brain, as well as for
      pharmacological design of various types of new drugs.

PMID- 22131940
TI  - Neuroprotection: the emerging concept of restorative neural stem cell biology for
      the treatment of neurodegenerative diseases.
AB  - During the past decades Neural Stem Cells have been considered as an alternative
      source of cells to replace lost neurons and NSC transplantation has been
      indicated as a promising treatment for neurodegenerative disorders. Nevertheless,
      the current understanding of NSC biology suggests that, far from being mere spare
      parts for cell replacement therapies, NSCs could play a key role in the
      pharmacology of neuroprotection and become protagonists of innovative treatments
      for neurodegenerative diseases. Here, we review this new emerging concept of NSC
      biology.

PMID- 22131939
TI  - Oxidative stress in schizophrenia.
AB  - Increasing evidence indicates that oxidative damage exists in schizophrenia.
      Available literature about possible mechanisms of oxidative stress induction was
      reviewed. Furthermore, possibilities of measuring biomarkers of schizophrenia
      outside the central nervous system compartment, their specificity for different
      types of schizophrenia and potential therapeutic strategies to prevent oxidative
      injuries in schizophrenia were discussed. Data were extracted from published
      literature found in Medline, Embase, Biosis, Cochrane and Web of Science,
      together with hand search of references. Search terms were: schizophrenia,
      oxidative stress, antipsychotics, antioxidants and fatty acids. Finding a
      sensitive, specific and non invasive biomarker of schizophrenia, which could be
      measured in peripheral tissue, still stays an important task. Antioxidant
      enzymes, markers of lipid peroxidation, oxidatively modified proteins and DNA are
      most commonly used. As it considers the supplemental therapy, according to our
      meta-analysis vitamin E could potentially improve tardive dyskinesia, while for
      the effect of therapy with polyunsaturated fatty acids there is no clear
      evidence. Oxidative stress is a part of the pathology in schizophrenia and
      appears as a promising field to develop new therapeutic strategies. There is a
      need for well designed, placebo controlled trials with supplementation therapy in
      schizophrenia.

PMID- 22131942
TI  - Nuclear Factor kappaB and Adenosine Receptors: Biochemical and Behavioral
      Profiling.
AB  - Adenosine is produced primarily by the metabolism of ATP and mediates its
      physiological actions by interacting primarily with adenosine receptors (ARs) on
      the plasma membranes of different cell types in the body. Activation of these G
      protein-coupled receptors promotes activation of diverse cellular signaling
      pathways that define their tissue-specific functions. One of the major actions of
      adenosine is cytoprotection, mediated primarily via two ARs - A(1) (A(1)AR) and
      A(3) (A(3)AR). These ARs protect cells exposed to oxidative stress and are also
      regulated by oxidative stress. Stress-mediated regulation of ARs involves two
      prominent transcription factors - activator protein-1 (AP-1) and nuclear factor
      (NF)-kappaB - that mediate the induction of genes important in cell survival.
      Mice that are genetically deficient in the p50 subunit of NF-kappaB (i.e., p50
      knock-out mice) exhibit altered expression of A(1)AR and A(2A)AR and demonstrate
      distinct behavioral phenotypes under normal conditions or after drug challenges.
      These effects suggest an important role for NF-kappaB in dictating the level of
      expression of ARs in vivo, in regulating the cellular responses to stress, and in
      modifying behavior.

PMID- 22131941
TI  - Neurochemical and neuropharmacological aspects of circadian disruptions: an
      introduction to asynchronization.
AB  - Circadian disruptions are common in modern society, and there is an urgent need
      for effective treatment strategies. According to standard diagnostic criteria,
      most adolescents showing both insomnia and daytime sleepiness are diagnosed as
      having behavioral-induced sleep efficiency syndrome resulting from insomnia due
      to inadequate sleep hygiene. However, a simple intervention of adequate sleep
      hygiene often fails to treat them. As a solution to this clinical problem, the
      present review first overviews the basic neurochemical and neuropharmachological
      aspects of sleep and circadian rhythm regulation, then explains several circadian
      disruptions from similar viewpoints, and finally introduces the clinical notion
      of asynchronization. Asynchronization is designated to explain the
      pathophysiology/pathogenesis of exhibition of both insomnia and hypersomnia in
      adolescents, which comprises disturbances in various aspects of biological
      rhythms. The major triggers for asynchronization are considered to be a
      combination of light exposure during the night, which disturbs the biological
      clock and decreases melatonin secretion, as well as a lack of light exposure in
      the morning, which prohibits normal synchronization of the biological clock to
      the 24-hour cycle of the earth and decreases the activity of serotonin. In the
      chronic phase of asynchronization, involvement of both wake- and sleep-promoting
      systems is suggested. Both conventional and alternative therapeutic approaches
      for potential treatment of asynchronization are suggested.

PMID- 22131943
TI  - Medical management of Parkinson's disease: focus on neuroprotection.
AB  - Neuroprotection refers to the protection of neurons from excitotoxicity,
      oxidative stress and apoptosis as principal mechanisms of cell loss in a variety
      of diseases of the central nervous system. Our interest in Parkinson's disease
      (PD) treatment is focused on drugs with neuroprotective properties in preclinical
      experiments and evidence-based efficacy in human subjects. To this date,
      neuroprotection has never been solidly proven in clinical trials but recent
      adequate markers and/or strategies to study and promote this important goal are
      described. A myriad of compounds with protective properties in cell cultures and
      animal models yield to few treatments in clinical practice. At present, markers
      of neuronal vitality, disease modifying effects and long term clinical stability
      are the elements searched for in clinical trials. This review highlights new
      strategies to monitor patients with PD. Currently, neuroprotection in subjects
      has not been solidly achieved for selegiline and pramipexole; however, a recent
      rasagiline trial design is showing new indications of disease course modifying
      effects. In neurological practice, it is of utmost importance to take into
      account the potential neuroprotection exerted by a treatment in conjunction with
      its symptomatic efficacy.

PMID- 22131944
TI  - Human endogenous retroviruses in multiple sclerosis: potential for novel neuro
      pharmacological research.
AB  - There is growing evidence that the env genes of two or more human endogenous
      retroviruses (HERVs) of the W family are contributing to the inflammatory
      processes, and thus to the pathogenesis, of multiple sclerosis (MS). Increasing
      understanding of the human endogenous retroviral locus, ERVWE1, and the putative
      multiple sclerosis associated retrovirus, or MSRV, and in particular of the HERV
      W env sequences associated with these, offers the potential of new lines of
      pharmacological research that might assist diagnosis, prognosis and therapy of
      multiple sclerosis.

PMID- 22131945
TI  - Carbohydrate reward and psychosis: an explanation for neuroleptic induced weight
      gain and path to improved mental health?
AB  - Evidence links dopamine release in the mid-brain to the pathophysiology of
      psychosis, addiction and reward. Repeated ingestion of refined carbohydrate may
      stimulate the same mesolimbic dopaminergic pathway, rewarding such eating
      behaviour and resulting in excessive food intake along with obesity. In this
      paper, we explore the role of dopamine in reward and psychosis, and discuss how
      reward pathways may contribute to the weight gain that commonly follows
      antipsychotic drug use, in people with psychotic illness. Our theory also
      explains the frequent co-occurrence of substance abuse and psychosis. From our
      hypothesis, we discuss the use of carbohydrate modified diets as an adjunctive
      treatment for people with psychosis.

PMID- 22131948
TI  - Optimization of xylanase production by Streptomyces sp. P12-137 using response
      surface methodology and central composite design.
AB  - Response surface methodology and central composite design were used to optimize a
      biosynthesis medium for the production of xylanases by Streptomyces sp. P12-137
      in submerged fermentation culture at pH 5.0, with wheat bran as substrate. The
      three variables involved in this research were the wheat bran, potassium nitrate
      and xylose concentrations. Statistical analysis of the results showed that, in
      the range studied, xylose and potassium nitrate concentrations had a significant
      effect on xylanase production. The optimized biosynthesis medium contained (in %,
      w/v): wheat bran 1.0, KNO(3) 1.0, xylose 0.5. This medium resulted in a 3-fold
      increased level of the xylanase (27.77 UA/ml) production compared to the initial
      level (8.30 UA/ml) after 120 h of fermentation, whereas the value predicted by
      the quadratic model was 26.45 UA/ml.

PMID- 22131946
TI  - Kynurenine metabolites and migraine: experimental studies and therapeutic
      perspectives.
AB  - Migraine is one of the commonest neurological disorders. Despite intensive
      research, its exact pathomechanism is still not fully understood and effective
      therapy is not always available. One of the key molecules involved in migraine is
      glutamate, whose receptors are found on the first-, second- and third-order
      trigeminal neurones and are also present in the migraine generators, including
      the dorsal raphe nucleus, nucleus raphe magnus, locus coeruleus and
      periaqueductal grey matter. Glutamate receptors are important in cortical
      spreading depression, which may be the electrophysiological correlate of migraine
      aura. The kynurenine metabolites, endogenous tryptophan metabolites, include
      kynurenic acid (KYNA), which exerts a blocking effect on ionotropic glutamate and
      alpha7-nicotinic acetylcholine receptors. Thus, KYNA and its derivatives may act
      as modulators at various levels of the pathomechanism of migraine. They can give
      rise to antinociceptive effects at the periphery, in the trigeminal nucleus
      caudalis, and may also act on migraine generators and cortical spreading
      depression. The experimental data suggest that KYNA or its derivatives might
      offer a novel approach to migraine therapy.

PMID- 22131947
TI  - Kainic Acid-induced neurotoxicity: targeting glial responses and glia-derived
      cytokines.
AB  - Glutamate excitotoxicity contributes to a variety of disorders in the central
      nervous system, which is triggered primarily by excessive Ca(2+) influx arising
      from overstimulation of glutamate receptors, followed by disintegration of the
      endoplasmic reticulum (ER) membrane and ER stress, the generation and
      detoxification of reactive oxygen species as well as mitochondrial dysfunction,
      leading to neuronal apoptosis and necrosis. Kainic acid (KA), a potent agonist to
      the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate class
      of glutamate receptors, is 30-fold more potent in neuro-toxicity than glutamate.
      In rodents, KA injection resulted in recurrent seizures, behavioral changes and
      subsequent degeneration of selective populations of neurons in the brain, which
      has been widely used as a model to study the mechanisms of neurodegenerative
      pathways induced by excitatory neurotransmitter. Microglial activation and
      astrocytes proliferation are the other characteristics of KA-induced
      neurodegeneration. The cytokines and other inflammatory molecules secreted by
      activated glia cells can modify the outcome of disease progression. Thus, anti
      oxidant and anti-inflammatory treatment could attenuate or prevent KA-induced
      neurodegeneration. In this review, we summarized updated experimental data with
      regard to the KA-induced neurotoxicity in the brain and emphasized glial
      responses and glia-oriented cytokines, tumor necrosis factor-alpha, interleukin
      (IL)-1, IL-12 and IL-18.

PMID- 22131949
TI  - Purification and characterization of chitinase from Alcaligenes faecalis AU02 by
      utilizing marine wastes and its antioxidant activity.
AB  - Marine waste is an abundant renewable source for the recovery of several value
      added metabolites with potential industrial applications. This study describes
      the production of chitinase on marine waste, with the subsequent use of the same
      marine waste for the extraction of antioxidants. A chitinase-producing bacterium
      isolated from seafood effluent was identified as Alcaligenes faecalis AU02.
      Optimal chitinase production was obtained in culture conditions of 37 degrees C
      for 72 h in 100 ml medium containing 1% shrimp and crab shell powder (1:1) (w/v),
      0.1% K(2)HPO(4), and 0.05% MgSO(4).7H(2)O. The molecular weight of chitinase was
      determined by SDS-PAGE to be 36 kDa. The optimum pH, temperature, pH stability,
      and thermal stability of chitinase were about 8, 37 degrees C, 5-12, and 40-80
      degrees C, respectively. The antioxidant activity of A. faecalis AU02 culture
      supernatant was determined through scavenging ability on 1,1-diphenyl-2
      picrylhydrazyl (DPPH) as 84%, and the antioxidant compound was characterized by
      TLC and its FT-IR spectrum. The present study proposed that marine wastes can be
      utilized to generate a high-value-added product and that pharmacological studies
      can extend its use to the field of medicine.

PMID- 22131951
TI  - Capilloquinol: a novel farnesyl quinol from the Dongsha atoll soft coral
      Sinularia capillosa.
AB  - Capilloquinol (1), possessing an unprecedented farnesyl quinoid skeleton, was
      isolated from the Dongsha Atoll soft coral Sinularia capillosa. The structure of
      capilloquinol was elucidated by extensive analysis of spectroscopic data. The
      cytotoxicity and antiviral activity against human cytomegalovirus of 1 was
      evaluated in vitro.

PMID- 22131952
TI  - Frajunolides L-O, four new 8-Hydroxybriarane diterpenoids from the Gorgonian
      Junceella fragilis.
AB  - Four new 8-hydroxybriarane diterpenoids, frajunolides L-O (1-4), were isolated
      from the Taiwanese gorgonian Junceella fragilis. The structures of compounds 1-4
      were elucidated based on spectroscopic analysis, especially 2D NMR ((1)H-(1)H
      COSY, HSQC, HMBC and NOESY) and HRMS. Compounds 1 and 4 showed weak anti
      inflammatory activity as tested by superoxide anion generation and elastase
      release by human neutrophil in response to fMLP/CB. Compound 3 showed selective
      inhibition on elastase release in vitro.

PMID- 22131950
TI  - Production of bioactive secondary metabolites by marine vibrionaceae.
AB  - Bacteria belonging to the Vibrionaceae family are widespread in the marine
      environment. Today, 128 species of vibrios are known. Several of them are
      infamous for their pathogenicity or symbiotic relationships. Despite their
      ability to interact with eukaryotes, the vibrios are greatly underexplored for
      their ability to produce bioactive secondary metabolites and studies have been
      limited to only a few species. Most of the compounds isolated from vibrios so far
      are non-ribosomal peptides or hybrids thereof, with examples of N-containing
      compounds produced independent of nonribosomal peptide synthetases (NRPS). Though
      covering a limited chemical space, vibrios produce compounds with attractive
      biological activities, including antibacterial, anticancer, and antivirulence
      activities. This review highlights some of the most interesting structures from
      this group of bacteria. Many compounds found in vibrios have also been isolated
      from other distantly related bacteria. This cosmopolitan occurrence of
      metabolites indicates a high incidence of horizontal gene transfer, which raises
      interesting questions concerning the ecological function of some of these
      molecules. This account underlines the pending potential for exploring new
      bacterial sources of bioactive compounds and the challenges related to their
      investigation.

PMID- 22131953
TI  - Characterization of a novel serine protease inhibitor gene from a marine
      metagenome.
AB  - A novel serine protease inhibitor (serpin) gene designated as Spi1C was cloned
      via the sequenced-based screening of a metagenomic library from uncultured marine
      microorganisms. The gene had an open reading frame of 642 base pairs, and encoded
      a 214-amino acid polypeptide with a predicted molecular mass of about 28.7 kDa.
      The deduced amino acid sequence comparison and phylogenetic analysis indicated
      that Spi1C and some partial proteinase inhibitor I4 serpins were closely related.
      Functional characterization demonstrated that the recombinant Spi1C protein could
      inhibit a series of serine proteases. The Spi1C protein exhibited inhibitory
      activity against alpha-chymotrypsin and trypsin with K(i) values of around 1.79 *
      10(-8) and 1.52 * 10(-8) M, respectively. No inhibition activity was exhibited
      against elastase. Using H-d-Phe-Pip-Arg-pNA as the chromogenic substrate, the
      optimum pH and temperature of the inhibition activity against trypsin were 7.0
      8.0 and 25  degrees C, respectively. The identification of a novel serpin gene
      underscores the potential of marine metagenome screening for novel biomolecules.

PMID- 22131954
TI  - A new anthracene derivative from marine Streptomyces sp. W007 exhibiting highly
      and selectively cytotoxic activities.
AB  - A new anthracene derivative, 3-hydroxy-1-keto-3-methyl-8-methoxy-1,2,3, 4
      tetrahydro-benz[alpha]anthracene, was isolated from the marine strain
      Streptomyces sp. W007, and its structure was established by spectroscopic
      analysis including mass spectra, 1D- and 2D-NMR ((1)H-(1)H COSY, HMBC, HSQC and
      NOESY) experiments. 3-hydroxy-1-keto-3-methyl-8-methoxy-1,2,3,4-tetrahydro
      benz[alpha]anthracene showed cytotoxicity against human lung adenocarcinoma cell
      line A549.

PMID- 22131956
TI  - Menelloides C and D, new sesquiterpenoids from the Gorgonian coral Menella sp.
AB  - Two new metabolites, including a lindenane-type sesquiterpenoid, menelloide C
      (1), and a germacrane-type sesquiterpenoid, menelloide D (2), were isolated from
      a Formosan gorgonian coral identified as Menella sp. The structures of 1 and 2
      were established by spectroscopic methods and 2 displayed a weak inhibitory
      effect on the release of elastase by human neutrophils.

PMID- 22131955
TI  - Biomedical exploitation of chitin and chitosan via mechano-chemical disassembly,
      electrospinning, dissolution in imidazolium ionic liquids, and supercritical
      drying.
AB  - Recently developed technology permits to optimize simultaneously surface area,
      porosity, density, rigidity and surface morphology of chitin-derived materials of
      biomedical interest. Safe and ecofriendly disassembly of chitin has superseded
      the dangerous acid hydrolysis and provides higher yields and scaling-up
      possibilities: the chitosan nanofibrils are finding applications in reinforced
      bone scaffolds and composite dressings for dermal wounds. Electrospun chitosan
      nanofibers, in the form of biocompatible thin mats and non-wovens, are being
      actively studied: composites of gelatin + chitosan + polyurethane have been
      proposed for cardiac valves and for nerve conduits; fibers are also manufactured
      from electrospun particles that self-assemble during subsequent freeze-drying.
      Ionic liquids (salts of alkylated imidazolium) are suitable as non-aqueous
      solvents that permit desirable reactions to occur for drug delivery purposes. Gel
      drying with supercritical CO(2) leads to structures most similar to the
      extracellular matrix, even when the chitosan is crosslinked, or in combination
      with metal oxides of interest in orthopedics.

PMID- 22131957
TI  - nardosinane-type sesquiterpenoids from the formosan soft coral Paralemnalia
      thyrsoides.
AB  - Five new nardosinane-type sesquiterpenoids, paralemnolins Q-U (1-5), along with
      three known compounds (6-8), were isolated from the Formosan soft coral
      Paralemnalia thyrsoides. The structures of new metabolites were elucidated on the
      basis of extensive spectroscopic methods, and the absolute configuration of 1 was
      determined by the application of Mosher's method on 1. Among these metabolites, 1
      and 3 are rarely found nardosinane-type sesquiterpenoids, possessing novel
      polycyclic structures. Compounds 1, 3, 6 and 7 were found to possess
      neuroprotective activity.

PMID- 22131958
TI  - Synthesis and alpha-glucosidase inhibitory mechanisms of bis(2,3-dibromo-4,5
      dihydroxybenzyl) ether, a potential marine bromophenol alpha-glucosidase
      inhibitor.
AB  - Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE), derived from the marine algae,
      is a potential alpha-glucosidase inhibitor for type 2 diabetes treatment. In the
      present study, a synthetic route was established as a valid approach to obtain
      BDDE. Fluorescence spectra, circular dichroism spectra and molecular docking
      methods were employed to elucidate the inhibitory mechanisms of BDDE against
      alpha-glucosidase. The results showed that BDDE could be prepared effectively and
      efficiently with the established synthetic methods. Synthetic BDDE bound with
      alpha-glucosidase and induced minor conformational changes of the enzyme. The
      docking results indicated the interaction between BDDE and alpha-glucosidase was
      driven by both hydrophobic forces and hydrogen bonds. The docked BDDE molecule
      was completely buried in the alpha-glucosidase binding pocket with part of the
      molecule reaching the catalytic center and overlapping with the position of
      glucose, and the rest of the molecule extending towards protein surface. This
      study provides useful information for the understanding of the BDDE-alpha
      glucosidase interaction and for the development of novel alpha-glucosidase
      inhibitors.

PMID- 22131959
TI  - NMR-based metabolomic investigations on the differential responses in adductor
      muscles from two pedigrees of Manila clam Ruditapes philippinarum to Cadmium and
      Zinc.
AB  - Manila clam Ruditapes philippinarum is one of the most important economic species
      in shellfishery in China due to its wide geographic distribution and high
      tolerance to environmental changes (e.g., salinity, temperature). In addition,
      Manila clam is a good biomonitor/bioindicator in "Mussel Watch Programs" and
      marine environmental toxicology. However, there are several pedigrees of R.
      philippinarum distributed in the marine environment in China. No attention has
      been paid to the biological differences between various pedigrees of Manila
      clams, which may introduce undesirable biological variation in toxicology
      studies. In this study, we applied NMR-based metabolomics to detect the
      biological differences in two main pedigrees (White and Zebra) of R.
      philippinarum and their differential responses to heavy metal exposures (Cadmium
      and Zinc) using adductor muscle as a target tissue to define one sensitive
      pedigree of R. philippinarum as biomonitor for heavy metals. Our results
      indicated that there were significant metabolic differences in adductor muscle
      tissues between White and Zebra clams, including higher levels of alanine,
      glutamine, hypotaurine, phosphocholine and homarine in White clam muscles and
      higher levels of branched chain amino acids (valine, leucine and isoleucine),
      succinate and 4-aminobutyrate in Zebra clam muscles, respectively. Differential
      metabolic responses to heavy metals between White and Zebra clams were also
      found. Overall, we concluded that White pedigree of clam could be a preferable
      bioindicator/biomonitor in marine toxicology studies and for marine heavy metals
      based on the relatively high sensitivity to heavy metals.

PMID- 22131961
TI  - Enhancement of lutein production in Chlorella sorokiniana (Chorophyta) by
      improvement of culture conditions and random mutagenesis.
AB  - Chlorella sorokiniana has been selected for lutein production, after a screening
      of thirteen species of microalgae, since it showed both a high content in this
      carotenoid and a high growth rate. The effects of several nutritional and
      environmental factors on cell growth and lutein accumulation have been studied.
      Maximal specific growth rate and lutein content were attained at 690 MUmol
      photons m(-2) s(-1), 28  degrees C, 2 mM NaCl, 40 mM nitrate and under
      mixotrophic conditions. In general, optimal conditions for the growth of this
      strain also lead to maximal lutein productivity. High lutein yielding mutants of
      C. sorokiniana have been obtained by random mutagenesis, using N-methyl-N'-nitro
      nitrosoguanidine (MNNG) as a mutagen and selecting mutants by their resistance to
      the inhibitors of the carotenogenic pathway nicotine and norflurazon. Among the
      mutants resistant to the herbicides, those exhibiting both high content in lutein
      and high growth rate were chosen. Several mutants exhibited higher contents in
      this carotenoid than the wild type, showing, in addition, either a similar or
      higher growth rate than the latter strain. The mutant MR-16 exhibited a 2.0-fold
      higher volumetric lutein content than that of the wild type, attaining values of
      42.0 mg L(-1) and mutants DMR-5 and DMR-8 attained a lutein cellular content of
      7.0 mg g(-1) dry weight. The high lutein yield exhibited by C. sorokiniana makes
      this microalga an excellent candidate for the production of this commercially
      interesting pigment.

PMID- 22131960
TI  - Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge
      of potential relevance in cancer treatment.
AB  - Despite intense efforts to develop non-cytotoxic anticancer treatments, effective
      agents are still not available. Therefore, novel apoptosis-inducing drug leads
      that may be developed into effective targeted cancer therapies are of interest to
      the cancer research community. Targeted cancer therapies affect specific aberrant
      apoptotic pathways that characterize different cancer types and, for this reason,
      it is a more desirable type of therapy than chemotherapy or radiotherapy, as it
      is less harmful to normal cells. In this regard, marine sponge derived
      metabolites that induce apoptosis continue to be a promising source of new drug
      leads for cancer treatments. A PubMed query from 01/01/2005 to 31/01/2011
      combined with hand-curation of the retrieved articles allowed for the
      identification of 39 recently confirmed apoptosis-inducing anticancer lead
      compounds isolated from the marine sponge that are selectively discussed in this
      review.

PMID- 22131962
TI  - The relevance of marine chemical ecology to plankton and ecosystem function: an
      emerging field.
AB  - Marine chemical ecology comprises the study of the production and interaction of
      bioactive molecules affecting organism behavior and function. Here we focus on
      bioactive compounds and interactions associated with phytoplankton, particularly
      bloom-forming diatoms, prymnesiophytes and dinoflagellates. Planktonic bioactive
      metabolites are structurally and functionally diverse and some may have multiple
      simultaneous functions including roles in chemical defense (antipredator,
      allelopathic and antibacterial compounds), and/or cell-to-cell signaling (e.g.,
      polyunsaturated aldehydes (PUAs) of diatoms). Among inducible chemical defenses
      in response to grazing, there is high species-specific variability in the effects
      on grazers, ranging from severe physical incapacitation and/or death to no
      apparent physiological response, depending on predator susceptibility and
      detoxification capability. Most bioactive compounds are present in very low
      concentrations, in both the producing organism and the surrounding aqueous
      medium. Furthermore, bioactivity may be subject to synergistic interactions with
      other natural and anthropogenic environmental toxicants. Most, if not all
      phycotoxins are classic secondary metabolites, but many other bioactive
      metabolites are simple molecules derived from primary metabolism (e.g., PUAs in
      diatoms, dimethylsulfoniopropionate (DMSP) in prymnesiophytes). Producing cells
      do not seem to suffer physiological impact due to their synthesis. Functional
      genome sequence data and gene expression analysis will provide insights into
      regulatory and metabolic pathways in producer organisms, as well as
      identification of mechanisms of action in target organisms. Understanding
      chemical ecological responses to environmental triggers and chemically-mediated
      species interactions will help define crucial chemical and molecular processes
      that help maintain biodiversity and ecosystem functionality.

PMID- 22131963
TI  - Controlled release of diclofenac from matrix polymer of chitosan and oxidized
      konjac glucomannan.
AB  - The controlled release of diclofenac sodium (DFNa) from a chitosan-oxidized
      konjac glucomannan (CTS-OKG) polymer film was studied. Konjac glucomannan (KGM)
      was initially oxidized by sodium periodate and then cross-linked to CTS via imine
      bonds (-C=N-) to form the new CTS-OKG copolymer. The DFNa loaded CTS-OKG polymers
      were characterized by Fourier transformed infrared spectroscopy (FT-IR) and X-ray
      diffractometry (XRD). Finally, the release profiles of DFNa from the CTS-OKG
      polymer matrices were evaluated in a simulated gastrointestinal fluid system
      comprised of two hours in simulated gastric fluid (SGF; pH 1.2) followed by 24 h
      in simulated intestinal fluid (SIF; pH 7.4). A 1:2:1 (w/w/w) ratio of
      CTS:OKG:DFNa prepared at room temperature for 3 hours gave the highest %
      encapsulation efficiency (EE) of 95.6 +/- 0.6 and resulted in a minimal release
      of DFNa (<1% over 2 h) in SGF (pH 1.2) and a significantly improved sustained
      release in SIF (pH 7.4) with ~6% and 19% release over 8 and 24 h, respectively),
      some 15- and five-fold lower than that of the two commercial DFNa preparations,
      Diclosian and Voltaren. This formulation may be used for further study as a long
      term intestine controlled release drug model (at least 3 days).

PMID- 22131965
TI  - The neural basis of predicting the outcomes of imagined actions.
AB  - A key feature of human intelligence is the ability to predict the outcomes of
      one's own actions prior to executing them. Action values are thought to be
      represented in part in the dorsal and ventral medial prefrontal cortex (mPFC),
      yet current studies have focused on the value of executed actions rather than the
      anticipated value of a planned action. Thus, little is known about the neural
      basis of how individuals think (or fail to think) about their actions and the
      potential consequences before they act. We scanned individuals with fMRI while
      they thought about performing actions that they knew would likely be rewarded or
      unrewarded. Here we show that merely imagining an unrewarded action, as opposed
      to imagining a rewarded action, increases activity in the dorsal anterior
      cingulate cortex, independently of subsequent actions. This activity overlaps
      with regions that respond to actual unrewarded actions. The findings show a
      distinct network that signals the prospective outcomes of one's possible actions.
      A number of clinical disorders such as schizophrenia and drug abuse involve a
      failure to take the potential consequences of an action into account prior to
      acting. Our results thus suggest how dysfunctions of the mPFC may contribute to
      such failures.

PMID- 22131964
TI  - Marine polysaccharides: a source of bioactive molecules for cell therapy and
      tissue engineering.
AB  - The therapeutic potential of natural bioactive compounds such as polysaccharides,
      especially glycosaminoglycans, is now well documented, and this activity combined
      with natural biodiversity will allow the development of a new generation of
      therapeutics. Advances in our understanding of the biosynthesis, structure and
      function of complex glycans from mammalian origin have shown the crucial role of
      this class of molecules to modulate disease processes and the importance of a
      deeper knowledge of structure-activity relationships. Marine environment offers a
      tremendous biodiversity and original polysaccharides have been discovered
      presenting a great chemical diversity that is largely species specific. The study
      of the biological properties of the polysaccharides from marine eukaryotes and
      marine prokaryotes revealed that the polysaccharides from the marine environment
      could provide a valid alternative to traditional polysaccharides such as
      glycosaminoglycans. Marine polysaccharides present a real potential for natural
      product drug discovery and for the delivery of new marine derived products for
      therapeutic applications.

PMID- 22131967
TI  - Learning through the taste system.
AB  - Taste is the final arbiter of which chemicals from the environment will be
      admitted to the body. The action of swallowing a substance leads to a
      physiological consequence of which the taste system should be informed.
      Accordingly, taste neurons in the central nervous system are closely allied with
      those that receive input from the viscera so as to monitor the impact of a
      recently ingested substance. There is behavioral, anatomical,
      electrophysiological, gene expression, and neurochemical evidence that the
      consequences of ingestion influence subsequent food selection through development
      of either a conditioned taste aversion (CTA) (if illness ensues) or a conditioned
      taste preference (CTP) (if nutrition). This ongoing communication between taste
      and the viscera permits the animal to tailor its taste system to its individual
      needs over a lifetime.

PMID- 22131966
TI  - Role of GSK3 Signaling in Neuronal Morphogenesis.
AB  - Glycogen synthase kinase 3 (GSK3) is emerging as a key regulator of several
      aspects of neuronal morphogenesis including neuronal polarization, axon growth,
      and axon branching. Multiple signaling pathways have been identified that control
      neuronal polarization, including PI3K, Rho-GTPases, Par3/6, TSC-mTOR, and PKA
      LKB1. However, how these pathways are coordinated is not clear. As GSK3 signaling
      exhibits crosstalk with each of these pathways it has the potential to integrate
      these polarity signals in the control neuronal polarization. After neurons
      establish polarity, GSK3 acts as an important signaling mediator in the
      regulation of axon extension and axon branching by transducing upstream signaling
      to reorganization of the axonal cytoskeleton, especially microtubules. Here we
      review the roles of GSK3 signaling in neuronal morphogenesis and discuss the
      underlying molecular mechanisms.

PMID- 22131968
TI  - Empirical and theoretical aspects of generation and transfer of information in a
      neuromagnetic source network.
AB  - Variability in source dynamics across the sources in an activated network may be
      indicative of how the information is processed within a network. Information
      theoretic tools allow one not only to characterize local brain dynamics but also
      to describe interactions between distributed brain activity. This study follows
      such a framework and explores the relations between signal variability and
      asymmetry in mutual interdependencies in a data-driven pipeline of non-linear
      analysis of neuromagnetic sources reconstructed from human
      magnetoencephalographic (MEG) data collected as a reaction to a face recognition
      task. Asymmetry in non-linear interdependencies in the network was analyzed using
      transfer entropy, which quantifies predictive information transfer between the
      sources. Variability of the source activity was estimated using multi-scale
      entropy, quantifying the rate of which information is generated. The empirical
      results are supported by an analysis of synthetic data based on the dynamics of
      coupled systems with time delay in coupling. We found that the amount of
      information transferred from one source to another was correlated with the
      difference in variability between the dynamics of these two sources, with the
      directionality of net information transfer depending on the time scale at which
      the sample entropy was computed. The results based on synthetic data suggest that
      both time delay and strength of coupling can contribute to the relations between
      variability of brain signals and information transfer between them. Our findings
      support the previous attempts to characterize functional organization of the
      activated brain, based on a combination of non-linear dynamics and temporal
      features of brain connectivity, such as time delay.

PMID- 22131969
TI  - Ras-ERK Signaling in Behavior: Old Questions and New Perspectives.
AB  - The role of Ras-ERK signaling in behavioral plasticity is well established.
      Inhibition studies using the blood-brain barrier permeable drug SL327 have
      conclusively demonstrated that this neuronal cell signaling cascade is a crucial
      component of the synaptic machinery implicated in the formation of various forms
      of long-term memory, from spatial learning to fear and operant conditioning.
      However, abnormal Ras-ERK signaling has also been linked to a number of
      neuropsychiatric conditions, including mental retardation syndromes
      ("RASopathies"), drug addiction, and l-DOPA induced dyskinesia (LID). The work
      recently done on these brain disorders has pointed to previously underappreciated
      roles of Ras-ERK in specific subsets of neurons, like GABAergic interneurons of
      the hippocampus or the cortex, as well as in the medium spiny neurons of the
      striatum. Here we will highlight the open questions related to Ras-ERK signaling
      in these behavioral manifestations and propose crucial experiments for the
      future.

PMID- 22131971
TI  - Binocular Rivalry Stimuli are Common but Rivalry is not.

PMID- 22131970
TI  - The human likeness dimension of the "uncanny valley hypothesis": behavioral and
      functional MRI findings.
AB  - The uncanny valley hypothesis (Mori, 1970) predicts differential experience of
      negative and positive affect as a function of human likeness. Affective
      experience of humanlike robots and computer-generated characters (avatars)
      dominates "uncanny" research, but findings are inconsistent. Importantly, it is
      unknown how objects are actually perceived along the hypothesis' dimension of
      human likeness (DOH), defined in terms of human physical similarity. To examine
      whether the DOH can also be defined in terms of effects of categorical perception
      (CP), stimuli from morph continua with controlled differences in physical human
      likeness between avatar and human faces as endpoints were presented. Two
      behavioral studies found a sharp category boundary along the DOH and enhanced
      visual discrimination (i.e., CP) of fine-grained differences between pairs of
      faces at the category boundary. Discrimination was better for face pairs
      presenting category change in the human-to-avatar than avatar-to-human direction
      along the DOH. To investigate brain representation of physical change and
      category change along the DOH, an event-related functional magnetic resonance
      imaging study used the same stimuli in a pair-repetition priming paradigm.
      Bilateral mid-fusiform areas and a different right mid-fusiform area were
      sensitive to physical change within the human and avatar categories,
      respectively, whereas entirely different regions were sensitive to the human-to
      avatar (caudate head, putamen, thalamus, red nucleus) and avatar-to-human
      (hippocampus, amygdala, mid-insula) direction of category change. These findings
      show that Mori's DOH definition does not reflect subjective perception of human
      likeness and suggest that future "uncanny" studies consider CP and the DOH's
      category structure in guiding experience of non-human objects.

PMID- 22131972
TI  - The need for the emergence of mathematical neuroscience: beyond computation and
      simulation.

PMID- 22131973
TI  - Tools for Brain-Computer Interaction: A General Concept for a Hybrid BCI.
AB  - The aim of this work is to present the development of a hybrid Brain-Computer
      Interface (hBCI) which combines existing input devices with a BCI. Thereby, the
      BCI should be available if the user wishes to extend the types of inputs
      available to an assistive technology system, but the user can also choose not to
      use the BCI at all; the BCI is active in the background. The hBCI might decide on
      the one hand which input channel(s) offer the most reliable signal(s) and switch
      between input channels to improve information transfer rate, usability, or other
      factors, or on the other hand fuse various input channels. One major goal
      therefore is to bring the BCI technology to a level where it can be used in a
      maximum number of scenarios in a simple way. To achieve this, it is of great
      importance that the hBCI is able to operate reliably for long periods,
      recognizing and adapting to changes as it does so. This goal is only possible if
      many different subsystems in the hBCI can work together. Since one research
      institute alone cannot provide such different functionality, collaboration
      between institutes is necessary. To allow for such a collaboration, a new concept
      and common software framework is introduced. It consists of four interfaces
      connecting the classical BCI modules: signal acquisition, preprocessing, feature
      extraction, classification, and the application. But it provides also the concept
      of fusion and shared control. In a proof of concept, the functionality of the
      proposed system was demonstrated.

PMID- 22131975
TI  - Neurons on a chip - toward high throughput network and pharmacology
      investigations.

PMID- 22131974
TI  - Automated electrophysiology makes the pace for cardiac ion channel safety
      screening.
AB  - The field of automated patch-clamp electrophysiology has emerged from the tension
      between the pharmaceutical industry's need for high-throughput compound screening
      versus its need to be conservative due to regulatory requirements. On the one
      hand, hERG channel screening was increasingly requested for new chemical
      entities, as the correlation between blockade of the ion channel coded by hERG
      and torsades de pointes cardiac arrhythmia gained increasing attention. On the
      other hand, manual patch-clamping, typically quoted as the "gold-standard" for
      understanding ion channel function and modulation, was far too slow (and,
      consequently, too expensive) for keeping pace with the numbers of compounds
      submitted for hERG channel investigations from pharmaceutical R&D departments. In
      consequence it became more common for some pharmaceutical companies to outsource
      safety pharmacological investigations, with a focus on hERG channel interactions.
      This outsourcing has allowed those pharmaceutical companies to build up
      operational flexibility and greater independence from internal resources, and
      allowed them to obtain access to the latest technological developments that
      emerged in automated patch-clamp electrophysiology - much of which arose in
      specialized biotech companies. Assays for nearly all major cardiac ion channels
      are now available by automated patch-clamping using heterologous expression
      systems, and recently, automated action potential recordings from stem-cell
      derived cardiomyocytes have been demonstrated. Today, most of the large
      pharmaceutical companies have acquired automated electrophysiology robots and
      have established various automated cardiac ion channel safety screening assays on
      these, in addition to outsourcing parts of their needs for safety screening.

PMID- 22131976
TI  - State-of-the-Art Automated Patch Clamp Devices: Heat Activation, Action
      Potentials, and High Throughput in Ion Channel Screening.
AB  - Ion channels are essential in a wide range of cellular functions and their
      malfunction underlies many disease states making them important targets in drug
      discovery. The availability of standardized cell lines expressing ion channels of
      interest lead to the development of diverse automated patch clamp (APC) systems
      with high-throughput capabilities. These systems are now available for drug
      screening, but there are limitations in the application range. However, further
      development of existing devices and introduction of new systems widen the range
      of possible experiments and increase throughput. The addition of well controlled
      and fast solution exchange, temperature control and the availability of the
      current clamp mode are required to analyze standard cell lines and excitable
      cells such as stem cell-derived cardiomyocytes in a more physiologically relevant
      environment. Here we describe two systems with different areas of applications
      that meet the needs of drug discovery researchers and basic researchers alike.
      The here utilized medium throughput APC device is a planar patch clamp system
      capable of recording up to eight cells simultaneously. Features such as
      temperature control and recordings in the current clamp mode are described here.
      Standard cell lines and excitable cells such as stem cell-derived cardiomyocytes
      have been used in the voltage clamp and current clamp modes with the view to
      finding new drug candidates and safety testing methods in a more physiologically
      relevant environment. The high-throughput system used here is a planar patch
      clamp screening platform capable of recording from 96 cells in parallel and
      offers a throughput of 5000 data points per day. Full dose response curves can be
      acquired from individual cells reducing the cost per data point. The data
      provided reveals the suitability and relevance of both APC platforms for drug
      discovery, ion channel research, and safety testing.

PMID- 22131977
TI  - Transmural heterogeneity of myofilament function and sarcomeric protein
      phosphorylation in remodeled myocardium of pigs with a recent myocardial
      infarction.
AB  - AIM: Transmural differences in sarcomeric protein composition and function across
      the left ventricular (LV) wall have been reported. We studied in pigs sarcomeric
      function and protein phosphorylation in subepicardial (EPI) and subendocardial
      (ENDO) layers of remote LV myocardium after myocardial infarction (MI), induced
      by left circumflex coronary artery ligation. METHODS: EPI and ENDO samples were
      taken 3 weeks after sham surgery (n = 12) or induction of MI (n = 12) at baseline
      (BL) and during beta-adrenergic receptor (betaAR) stimulation with dobutamine.
      Isometric force was measured in single cardiomyocytes at various [Ca(2+)] and 2.2
      MUm sarcomere length. RESULTS: In sham hearts, no significant transmural
      differences were observed in myofilament function or protein phosphorylation.
      Myofilament Ca(2+)-sensitivity was significantly higher in both EPI and ENDO of
      MI compared to sham hearts. Maximal force was significantly reduced in MI
      compared to sham, but solely in ENDO cells. A higher passive force was observed
      in MI hearts, but only in EPI cells. The proportion of stiff N2B isoform was
      higher in EPI than in ENDO in both sham and MI hearts, and a trend toward
      increased N2B-proportion appeared in MI EPI, but not MI Endo. Analysis of
      myofilament protein phosphorylation did not reveal significant transmural
      differences in phosphorylation of myosin binding protein C, desmin, troponin T,
      troponin I (cTnI), and myosin light chain 2 (MLC-2) both at BL and during betaAR
      stimulation with dobutamine infusion. A significant increase in MLC-2
      phosphorylation was observed during dobutamine only in sham. In addition, the
      increase in cTnI phosphorylation upon dobutamine was twofold lower in MI than in
      sham. CONCLUSION: Myofilament dysfunction is present in both EPI and ENDO in post
      MI remodeled myocardium, but shows a high degree of qualitative heterogeneity
      across the LV wall. These heterogeneous transmural changes in sarcomeric
      properties likely contribute differently to systolic vs. diastolic global LV
      dysfunction after MI.

PMID- 22131978
TI  - Exposure to prenatal infection and risk of schizophrenia.
AB  - We provide a brief review of findings supporting a role for prenatal infection in
      the etiology of schizophrenia. Our group and others have conducted birth cohort
      studies to address whether in utero exposure to infectious agents, prospectively
      documented by biomarker assays of archived maternal sera, and by detailed
      obstetric records, confer an increased risk of schizophrenia in adult offspring.
      Prenatal exposure to influenza, elevated toxoplasma antibody, rubella, genital
      reproductive infections, and other infections have been associated with an
      increased risk of schizophrenia among offspring. Animal models have supported
      these epidemiologic findings by revealing that maternal immune activation causes
      phenotypes analogous to those found in patients with schizophrenia. Given that
      exposure to microbial agents are preventable or treatable, they suggest that
      interventions to diminish the incidence of infection during pregnancy have the
      potential to prevent an appreciable proportion of schizophrenia cases. Given the
      clear genetic component to schizophrenia, future studies should include
      investigations of interactions between prenatal infection and susceptibility
      genes in the pathogenesis of schizophrenia.

PMID- 22131979
TI  - Adults with attention-deficit/hyperactivity disorder - a brain magnetic resonance
      spectroscopy study.
AB  - BACKGROUND: Impaired cognitive control in individuals with attention
      deficit/hyperactivity disorder (ADHD) may be related to a prefrontal cortical
      glutamatergic deficit. We assessed the glutamate level in the left and the right
      midfrontal region including the anterior cingulate cortex in adults with ADHD and
      healthy controls. METHODS: Twenty-nine adults with ADHD and 38 healthy controls
      were included. We used Proton Magnetic Resonance Imaging with single voxel point
      resolved spectroscopy to measure the ratio of glutamate to creatine (Glu/Cre) in
      the left and the right midfrontal region in the two groups. RESULTS: The ADHD
      group showed a significant reduction of Glu/Cre in the left midfrontal region
      compared to the controls. CONCLUSION: The reduction of Glu/Cre in the left
      midfrontal region in the ADHD group may reflect a glutamatergic deficit in
      prefrontal neuronal circuitry in adults with ADHD, resulting in problems with
      cognitive control.

PMID- 22131980
TI  - Utility versus pleasure: the grand paradox.

PMID- 22131981
TI  - Bilingualism and inhibitory control influence statistical learning of novel word
      forms.
AB  - We examined the influence of bilingual experience and inhibitory control on the
      ability to learn a novel language. Using a statistical learning paradigm,
      participants learned words in two novel languages that were based on the
      International Morse Code. First, participants listened to a continuous stream of
      words in a Morse code language to test their ability to segment words from
      continuous speech. Since Morse code does not overlap in form with natural
      languages, interference from known languages was minimized. Next, participants
      listened to another Morse code language composed of new words that conflicted
      with the first Morse code language. Interference in this second language was high
      due to conflict between languages and due to the presence of two colliding cues
      (compressed pauses between words and statistical regularities) that competed to
      define word boundaries. Results suggest that bilingual experience can improve
      word learning when interference from other languages is low, while inhibitory
      control ability can improve word learning when interference from other languages
      is high. We conclude that the ability to extract novel words from continuous
      speech is a skill that is affected both by linguistic factors, such as bilingual
      experience, and by cognitive abilities, such as inhibitory control.

PMID- 22131982
TI  - Valence, arousal, and cognitive control: a voluntary task-switching study.
AB  - The present study focused on the interplay between arousal, valence, and
      cognitive control. To this end, we investigated how arousal and valence
      associated with affective stimuli influenced cognitive flexibility when switching
      between tasks voluntarily. Three hypotheses were tested. First, a valence
      hypothesis that states that the positive valence of affective stimuli will
      facilitate both global and task-switching performance because of increased
      cognitive flexibility. Second, an arousal hypothesis that states that arousal,
      and not valence, will specifically impair task-switching performance by
      strengthening the previously executed task-set. Third, an attention hypothesis
      that states that both cognitive and emotional control ask for limited attentional
      resources, and predicts that arousal will impair both global and task-switching
      performance. The results showed that arousal affected task-switching but not
      global performance, possibly by phasic modulations of the noradrenergic system
      that reinforces the previously executed task. In addition, positive valence only
      affected global performance but not task-switching performance, possibly by
      phasic modulations of dopamine that stimulates the general ability to perform in
      a multitasking environment.

PMID- 22131983
TI  - Prevention of Adiposity by the Oral Administration of beta-Cryptoxanthin.
AB  - beta-Cryptoxanthin (beta-CRX) is a carotenoid found in human blood. It is
      specifically rich in Satsuma mandarin (Citrus unshiu Marc.) but very little in
      other fruits or vegetables. Several reports indicate the health promoting
      benefits of beta-CRX. As we had reported visceral fat reduction on mildly obese
      male by the oral administration of beta-CRX, a detailed mechanism has not been
      identified. To identify the mechanism, obese model mouse, TSOD was used in the
      present study. Oral administration of beta-CRX repressed body weight, abdominal
      adipose tissue weight, and serum lipid concentrations on TSOD mice. The
      outstanding observation is the significant repression of adipocyte hypertrophy.
      DNA microarray analysis strongly indicates that the oral administration of beta
      CRX represses the inflammatory cytokine secretion and improves the lipid
      metabolism and the energy consumption. It also suggests these effects are partly
      mediated by PPAR-alpha, not only lipid metabolism and adipocyte differentiation
      control but possibly internal circadian clock modulation.

PMID- 22131984
TI  - Simultaneous parasympathetic and sympathetic activation reveals altered autonomic
      control of heart rate, vascular tension, and epinephrine release in anesthetized
      hypertensive rats.
AB  - Sympathetic hyperactivity and parasympathetic insufficiency characterize blood
      pressure (BP) control in genetic hypertension. This shift is difficult to
      investigate in anesthetized rats. Here we present a pharmacological approach to
      simultaneously provoke sympathetic and parasympathetic transmitter release, and
      identify their respective roles in the concomitant cardiovascular response. To
      stimulate transmitter release in anesthetized normotensive (WKY) and
      spontaneously hypertensive rats (SHR), we injected intravenously 4-aminopyridine
      (4-AP), a voltage-sensitive K(+) channel (K(V)) inhibitor. A femoral artery
      catheter monitored BP, an ascending aorta flow-probe recorded cardiac output and
      heart rate (HR). Total peripheral vascular resistance (TPVR) was calculated. 4-AP
      induced an immediate, atropine (muscarinic antagonist)- and hexamethonium
      (ganglion blocker)-sensitive bradycardia in WKY, and in both strains, a
      subsequent, sustained tachycardia, and norepinephrine but not epinephrine
      release. Reserpine (sympatholytic), nadolol (beta-adrenoceptor antagonist) or
      right vagal nerve stimulation eliminated the late tachycardia, adrenalectomy,
      scopolamine (central muscarinic antagonist) or hexamethonium did not. 4-AP
      increased TPVR, transiently in WKY but sustained in SHR. Yohimbine (alpha(2)
      adrenoceptor antagonist) prevented the TPVR down-regulation in WKY. Reserpine and
      prazosin (alpha(1)-adrenoceptor antagonist) eliminated the late vasoconstriction
      in SHR. Plasma epinephrine overflow increased in nadolol-treated SHR. Through
      inhibition of K(V), 4-AP activated parasympathetic ganglion transmission and
      peripheral, neuronal norepinephrine release. The sympathetic component dominated
      the 4-AP-HR-response in SHR. alpha(2)-adrenoceptor-dependent vasodilatation
      opposed norepinephrine-induced alpha(1)-adrenergic vasoconstriction in WKY, but
      not SHR. A betaAR-activated, probably vagal afferent mechanism, hampered
      epinephrine secretion in SHR. Thus, 4-AP activated the autonomic system and
      exposed mechanisms relevant to hypertensive disease.

PMID- 22131985
TI  - Recovering greater fungal diversity from pristine and diesel fuel contaminated
      sub-antarctic soil through cultivation using both a high and a low nutrient media
      approach.
AB  - Novel cultivation strategies for bacteria are widespread and well described for
      recovering greater diversity from the "hitherto" unculturable majority. While
      similar approaches have not yet been demonstrated for fungi it has been suggested
      that of the 1.5 million estimated species less than 5% have been recovered into
      pure culture. Fungi are known to be involved in many degradative processes,
      including the breakdown of petroleum hydrocarbons, and it has been speculated
      that in Polar Regions they contribute significantly to bioremediation of
      contaminated soils. Given the biotechnological potential of fungi there is a need
      to increase efforts for greater species recovery, particularly from extreme
      environments such as sub-Antarctic Macquarie Island. In this study, like the yet
      to-be cultured bacteria, high concentrations of nutrients selected for
      predominantly different fungal species to that recovered using a low nutrient
      media. By combining both media approaches to the cultivation of fungi from
      contaminated and non-contaminated soils, 91 fungal species were recovered,
      including 63 unidentified species. A preliminary biodegradation activity assay on
      a selection of isolates found that a high proportion of novel and described
      fungal species from a range of soil samples were capable of hydrocarbon
      degradation and should be characterized further.

PMID- 22131988
TI  - Measurement of redox potential in nanoecotoxicological investigations.
AB  - Redox potential has been identified by the Organisation for Economic Co-operation
      and Development (OECD) as one of the parameters that should be investigated for
      the testing of manufactured nanomaterials. There is still some ambiguity
      concerning this parameter, i.e., as to what and how to measure, particularly when
      in a nanoecotoxicological context. In this study the redox potentials of six
      nanomaterials (either zinc oxide (ZnO) or cerium oxide (CeO(2))) dispersions were
      measured using an oxidation-reduction potential (ORP) electrode probe. The
      particles under testing differed in terms of their particle size and dispersion
      stability in deionised water and in various ecotox media. The ORP values of the
      various dispersions and how they fluctuate relative to each other are discussed.
      Results show that the ORP values are mainly governed by the type of liquid media
      employed, with little contributions from the nanoparticles. Seawater was shown to
      have reduced the ORP value, which was attributed to an increase in the
      concentration of reducing agents such as sulphites or the reduction of dissolved
      oxygen concentration. The lack of redox potential value contribution from the
      particles themselves is thought to be due to insufficient interaction of the
      particles at the Pt electrode of the ORP probe.

PMID- 22131986
TI  - Biomarkers of acute kidney injury.
AB  - Acute kidney injury (AKI) is a common problem in both the inpatient and
      outpatient setting and often results from drug toxicities. Traditional methods of
      identifying AKI, through measurement of blood urea nitrogen and serum creatinine,
      are problematic in that they are slow to detect decreases in glomerular
      filtration rate (GFR) and are influenced by a variety of factors that are not
      related to GFR changes. The problems inherent in a creatinine-based diagnosis of
      AKI have impeded the development of proper therapeutics in AKI and posed problems
      in evaluating nephrotoxicity of drugs and other chemical exposures. In recent
      years, a number of new biomarkers of AKI with more favorable test characteristics
      than creatinine have been identified and studied in a variety of experimental and
      clinical settings. This review will consider the most well-established biomarkers
      and appraise the literature, with particular attention given to the use of
      biomarkers in identifying toxin-mediated AKI.

PMID- 22131987
TI  - Sulfurous gases as biological messengers and toxins: comparative genetics of
      their metabolism in model organisms.
AB  - Gasotransmitters are biologically produced gaseous signalling molecules. As gases
      with potent biological activities, they are toxic as air pollutants, and the
      sulfurous compounds are used as fumigants. Most investigations focus on medical
      aspects of gasotransmitter biology rather than toxicity toward invertebrate pests
      of agriculture. In fact, the pathways for the metabolism of sulfur containing
      gases in lower organisms have not yet been described. To address this deficit, we
      use protein sequences from Homo sapiens to query Genbank for homologous proteins
      in Caenorhabditis elegans, Drosophila melanogaster, and Saccharomyces cerevisiae.
      In C. elegans, we find genes for all mammalian pathways for synthesis and
      catabolism of the three sulfur containing gasotransmitters, H(2)S, SO(2) and COS.
      The genes for H(2)S synthesis have actually increased in number in C. elegans.
      Interestingly, D. melanogaster and Arthropoda in general, lack a gene for 3
      mercaptopyruvate sulfurtransferase, an enzym for H(2)S synthesis under reducing
      conditions.

PMID- 22131989
TI  - Effects of exposure to semiconductor nanoparticles on aquatic organisms.
AB  - Because of their unique physical, optical, and mechanical properties,
      nanomaterials hold great promise in improving on a wide variety of current
      technologies. Consequently, their use in research and consumer products is
      increasing rapidly, and contamination of the environment with various
      nanomaterials seems inevitable. Because surface waters receive pollutants and
      contaminants from many sources including nanoparticles and act as reservoirs and
      conduits for many environmental contaminants, understanding the potential impacts
      of nanoparticles on the organisms within these environments is critical to
      evaluating their potential toxicity. While there is much to be learned about
      interactions between nanomaterials and aquatic systems, there have been a number
      of recent reports of interactions of quantum dots (QDs) with aquatic environments
      and aquatic organisms. This review is focused on providing a summary of recent
      work investigating the impacts of quantum dots on aquatic organisms.

PMID- 22131990
TI  - HER-2 Evaluation in a Specific Gastric Cancer Population with the Highest Rate of
      Mortality in Spain.
AB  - Gastric cancer (GC) still represents the second cause of cancer-related death
      worldwide. Radical resection is the mainstay of early stages treatment with
      little impact on overall survival (OS) in the advanced ones. HER-2 is the most
      relevant biological factor involved. Purpose. This study aims to show the
      relationship between HER-2 positivity and survival in patients with completely
      resected GC. Methods. Retrospective study of GC patients diagnosed in 2003-2005
      at our institution. Surgical specimens underwent immunohistochemistry (IHC), and
      in cases +/++/+++ samples underwent also fluorescence in situ hybridisation
      (FISH) analyses of HER-2 and graduated according to experts' consensus. Results.
      120 cases included. Overall expression detected in 7.5%. Correlation between HER
      2 positive and female sex, advanced stages or histological grades, or intestinal
      type was detected. Early recurrences higher in HER-2 positive (66.6% versus
      35.4%, P = 0.048). The median DFS for c-erbB-2 positive was 15 months (range 2-67
      months), and OS was 25 months (range 10-67 months). In the case of patients with
      c-erbB-2, negative median DFS was 27 months (range 5-67 months) and OS for this
      sample is 47 months (range 29-67 months). Conclusions. These results emphasize
      the relevance of HER-2 positivity in GC as independent prognostic factor and
      support its current analyses in daily practice.

PMID- 22131991
TI  - Peroxisome Proliferator-Activated Receptor-gamma Ligands Alter Breast Cancer Cell
      Motility through Modulation of the Plasminogen Activator System.
AB  - We investigated peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      ligands effect on cell motility and the plasminogen activator system using normal
      MCF-10A and malignant MCF-10CA1 cell lines. Ciglitazone reduced both wound
      induced migration and chemotaxis. However, the effect was not reversed with
      pretreatment of cells with the PPAR-gamma-specific antagonist GW9662. Immunoblot
      analysis of conditioned media showed ciglitazone decreased plasminogen activator
      inhibitor-1 (PAI-1) in both cell lines; this effect was also unaltered by PPAR
      gamma antagonism. Alternatively, treatment with the omega-6 fatty acid
      arachidonic acid (ArA), but not the omega-3 fatty acid docosahexanoic acid,
      increased both MCF-10A cell migration and cell surface uPA activity. Pretreatment
      with a PPAR-gamma antagonist reversed these effects, suggesting that ArA mediates
      its effect on cell motility and uPA activity through PPAR-gamma activation.
      Collectively, the data suggest PPAR-gamma ligands have a differential effect on
      normal and malignant cell migration and the plasminogen activation system,
      resulting from PPAR-gamma-dependent and PPAR-gamma-independent effects.

PMID- 22131992
TI  - Familial papillary thyroid carcinoma: a retrospective analysis.
AB  - Background. Whether or not the familial form of papillary thyroid carcinoma is
      more aggressive than the sporadic form of the disease remains controversial.
      Methods. To explore this question and whether or not increased aggressiveness is
      more apparent in families with multiple affected members, we performed a chi
      square by trend analysis on our patients clinical and pathologic data comparing:
      first degree families with three or more affected members versus first degree
      families with two affected members versus sporadic cases of papillary thyroid
      carcinoma. Results. No statistically significant trends were seen for any
      presenting surgical pathology parameter, age at presentation, length of follow-up
      or gender distribution. The familial groups exhibited significant trends for
      higher rates of reoperation (P = 0.05) and/or requiring additional radioactive
      iodine therapy (P = 0.03), distant metastases (P = 0.003) and deaths (P = 0.01).
      These aggressive features were most apparent in certain families with three or
      more affected members. Conclusions. Using the chi square by trend analysis, a
      significant trend was seen for the familial form of papillary thyroid cancer to
      possess more aggressive features than the sporadic disease. Prompt recognition of
      the familial nature of the disease may provide earlier diagnosis and treatment in
      similarly affected family members.

PMID- 22131993
TI  - In vivo time-course imaging of tumor angiogenesis in colorectal liver metastases
      in the same living mice using two-photon laser scanning microscopy.
AB  - In vivo real-time visualization of the process of angiogenesis in secondary
      tumors in the same living animals presents a major challenge in metastasis
      research. We developed a technique for intravital imaging of colorectal liver
      metastasis development in live mice using two-photon laser scanning microscopy
      (TPLSM). We also developed time-series TPLSM in which intravital TPLSM procedures
      were performed several times over periods of days to months. Red fluorescent
      protein-expressing colorectal cancer cells were inoculated into the spleens of
      green fluorescent protein-expressing mice. First- and second-round intravital
      TPLSM allowed visualization of viable cancer cells (red) in hepatic sinusoids or
      the space of Disse. Third-round intravital TPLSM demonstrated liver metastatic
      colonies consisting of viable cancer cells and surrounding stroma with tumor
      vessels (green). In vivo time-course imaging of tumor angiogenesis in the same
      living mice using time-series TPLSM could be an ideal tool for antiangiogenic
      drug evaluation, reducing the effects of interindividual variation.

PMID- 22131994
TI  - Angiogenesis in head and neck cancer: a review of the literature.
AB  - Angiogenesis is a necessary process for tumor growth, progression and diffusion.
      In the last years many efforts have been made to understand the mechanisms
      necessary to the formation of new vessels in tumor tissue and how to integrate
      these findings in the treatment of different type of cancer. Thanks to these
      studies there are today many anti-angiogenic drugs with established activity in
      cancer and approved in clinical practice. Head and neck cancer is a common tumor
      worldwide that often has advanced stage at diagnosis and poor prognosis.
      Angiogenesis has a well recognized role in head and neck cancer progression and
      resistance to drugs and radiotherapy and many clinical trials has been conducted
      with antiangiogenic agents in this disease, even if they often showed limited
      efficacy. In this review we summarize the main trials published about
      angiogenesis in head and neck cancer with particular attention to factors
      involved in this process and the available data on the efficacy of treatment with
      anti-angiogenic agents in this disease.

PMID- 22131996
TI  - A systematic review of economic evaluations of chemoprophylaxis for tuberculosis.
AB  - Since treatment of active disease remains the priority for tuberculosis control,
      donors and governments need to be convinced that investing resources in
      chemoprophylaxis provides health benefits and is good value for money. The
      limited evidence of cost effectiveness has often been presented in a fragmentary
      and inconsistent fashion. Objective. This review is aimed at critically reviewing
      the evidence of cost effectiveness of chemoprophylaxis against tuberculosis,
      identifying the important knowledge gaps and the current issues which confront
      policy makers. Methods. A systematic search on economic evaluations for
      chemoprophylaxis against tuberculosis was carried out, and the selected studies
      were checked for quality assessment against a standard checklist. Results. The
      review provides evidence of the cost effectiveness of chemoprophylaxis for all
      age groups which suggests that current policy should be amended to include a
      focus on older adults. Seven of the eight selected studies were undertaken wholly
      in high income countries but there are considerable doubts about the
      transferability of the findings of the selected studies to low and middle income
      countries which have the greatest incidence of latent tuberculosis infection.
      Conclusion. There is a pressing need to expand the evidence base to low and
      middle income countries where the vast majority of sufferers from tuberculosis
      live.

PMID- 22131995
TI  - Biomarkers of cervical dysplasia and carcinoma.
AB  - Although cervical cytology screening has decreased the incidence of cervical
      cancer in industrialized countries, HPV-related cervical disease, including
      premalignant and malignant lesions, continues to represent a major burden on the
      health care system. Some of the problems include the potential for either under-
      or overtreatment of women due to decreased specificity of screening tests as well
      as significant interobserver variability in the diagnosis of cervical dysplastic
      lesions. Although not completely elucidated, the HPV-driven molecular mechanisms
      underlying the development of cervical lesions have provided a number of
      potential biomarkers for both diagnostic and prognostic use in the clinical
      management of these women.

PMID- 22131997
TI  - Research on Trypanosoma cruzi and Analysis of Inflammatory Infiltrate in
      Esophagus and Colon from Chronic Chagasic Patients with and without Mega.
AB  - To compare parasitism and inflammatory process in esophagus and colon from
      chronic chagasic patients, immunohistochemistry was carried out to research for
      T. cruzi and to evaluate the inflammatory infiltrate in the muscular and
      myenteric plexus in 39 esophagi (20 with and 19 without megaesophagus) and 50
      colons (25 with and 25 without megacolon). The frequency of T. cruzi in
      megaesophagus was 20%, and in megacolon it was 4%. No amastigotes were found in
      organs without mega; considering the total of esophagi (with and without mega),
      the frequency of T. cruzi would be 10% and 2% in the colon. Myositis and
      ganglionitis were more frequent and intense in organs with mega compared to those
      without mega, and in esophagus compared to colon. Qualitatively, inflammatory
      infiltration in esophagus and colon, with or without mega, was similar,
      consisting predominantly of T lymphocytes (CD3+), scarce macrophages (CD68+), and
      rare B lymphocytes (CD20+).

PMID- 22131999
TI  - A multicenter, randomized, parallel-group trial assessing compliance,
      tolerability, safety, and efficacy to treatment with grass allergy tablets in 261
      patients with grass pollen rhinoconjunctivitis.
AB  - Background. Allergen-specific sublingual immunotherapy (SLIT) is considered a
      causal treatment of respiratory allergies. Compliance to the SLIT is an important
      aspect for a positive clinical outcome. Study Aim. To evaluate if compliance with
      grass Allergy Immunotherapy Tablet (AIT) can be increased by providing an
      electronic compliance device (CED) (Memozax; a tablet-container with a
      programmable daily acoustic alarm). Patients and Methods. 261 patients with grass
      allergy were enrolled and randomized (1 : 1) to 1-year treatment with AIT
      (Grazax) using a CED (group A; n = 122) or without (Group B, n = 139). Compliance
      was measured through tablet count at each visit. Results. The 12-month
      compliance, mean (SD), in group A was 83% (21) and 83% (24) in group B. A total
      of 81% of patients reported a significant clinical improvement of symptoms after
      treatment in comparison with the previous year. No severe adverse reactions were
      observed in the study. Conclusion. Compliance to the treatment with AIT
      administered for 12 consecutive months is in general good. The use of CED is not
      associated with a greater compliance. AIT treatment was associated with a
      significant clinical improvement in >80% of patients with a good tolerability and
      safety profile.

PMID- 22132001
TI  - The accidental medical tourist.

PMID- 22132000
TI  - The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin
      Exacerbated Respiratory Disease in Mexican Population.
AB  - Aspirin exacerbated respiratory disease (AERD) is characterized by chronic
      hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity.
      The mechanisms which produce these manifestations of intolerance are not fully
      defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition,
      metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO)
      route, inducing increased synthesis of leukotrienes (LT). The biological
      plausibility of this model has led to the search for polymorphisms in genes
      responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We
      performed a genetic association study between IL8-251 (rs4073) and IL1B-511
      (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy
      control subjects. Using allelic discrimination by real-time PCR, we found
      statistically nonsignificant associations between AERD, ATA, and healthy control
      subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA
      genotype showed an increased frequency in the AERD patients versus the ATA group
      (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17-7.82). This is the
      first observation that IL1B polymorphisms are involved in AERD. Thus, future
      studies must investigate whether interleukin-1beta is released in the airways of
      AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

PMID- 22131998
TI  - Host cell signalling and leishmania mechanisms of evasion.
AB  - Leishmania parasites are able to secure their survival and propagation within
      their host by altering signalling pathways involved in the ability of macrophages
      to kill pathogens or to engage adaptive immune system. An important step in this
      immune evasion process is the activation of host protein tyrosine phosphatase SHP
      1 by Leishmania. SHP-1 has been shown to directly inactivate JAK2 and Erk1/2 and
      to play a role in the negative regulation of several transcription factors
      involved in macrophage activation. These signalling alterations contribute to the
      inactivation of critical macrophage functions (e.g., Nitric oxide, IL-12, and TNF
      alpha). Additionally, to interfere with IFN-gamma receptor signalling, Leishmania
      also alters several LPS-mediated responses. Recent findings from our laboratory
      revealed a pivotal role for SHP-1 in the inhibition of TLR-induced macrophage
      activation through binding to and inactivating IL-1-receptor-associated kinase 1
      (IRAK-1). Furthermore, we identified the binding site as an evolutionarily
      conserved ITIM-like motif, which we named kinase tyrosine-based inhibitory motif
      (KTIM). Collectively, a better understanding of the evasion mechanisms utilized
      by Leishmania parasite could help to develop more efficient antileishmanial
      therapies in the near future.

PMID- 22132002
TI  - Fever and abdominal pain in a returning traveller.

PMID- 22132003
TI  - Canadian consensus guidelines for the optimal use of maraviroc in the treatment
      of HIV-infected adults.
AB  - BACKGROUND AND OBJECTIVES: A Canadian group, consisting of six physicians and an
      HIV researcher with significant experience and knowledge in HIV management,
      reviewed the available data and developed guidelines for Canadian health care
      providers (who treat HIV infection) on the appropriate use of maraviroc (UK
      427,857) in HIV-infected adults. METHODS: Evidence from the published literature
      and conference presentations, as well as the expert opinions of the group members
      were considered and evaluated to develop the recommendations. Feedback on the
      draft recommendations was obtained from this core group, as well as from four
      other physicians across Canada with expertise in HIV treatment and experience
      with the use of maraviroc. The final recommendations represent the core group's
      consensus agreement once all feedback was considered. RESULTS/CONCLUSIONS:
      Recommendations were developed to guide physicians and other health care
      providers in the optimal use of maraviroc. The recommendations were considered in
      light of the fact that the decision to include maraviroc in an antiretroviral
      regimen depends not only on issues that concern all antiretroviral agents, such
      as efficacy, safety, resistance and drug interactions, but also on the issue of
      viral tropism, which is unique to maraviroc and other CCR5 inhibitors.

PMID- 22132004
TI  - Tuberculosis in children: New diagnostic blood tests.
AB  - The interferon-gamma-release assays were developed to overcome the pitfalls and
      logistic difficulties of the tuberculin skin test (TST) for the diagnosis of
      latent tuberculosis infection (LTBI). These blood tests measure the in vitro
      production of interferon-gamma by sensitized lymphocytes in response to
      Mycobacterium tuberculosis-specific antigens. Two interferon-gamma-release assays
      are registered for use in Canada: the QuantiFERON-TB Gold In-Tube assay
      (Cellestis Inc, Australia) and the T.SPOT-TB test (Oxford Immunotec, United
      Kingdom). Evaluation of these tests has been hampered by the lack of a gold
      standard for LTBI, and limited paediatric data on their use. It appears that they
      are more specific than the TST, and may be useful for evaluating TST-positive
      patients at low risk of true LTBI. Moreover, they may add sensitivity if used in
      addition to the TST in immunocompromised patients, very young children and close
      contacts of infectious adults. A summary of these tests, their limitations and
      their application to clinical paediatric practice are described.

PMID- 22132005
TI  - Antifungal agents for the treatment of systemic fungal infections in children.
AB  - Traditionally, the mainstay of systemic antifungal therapy has been amphotericin
      B deoxycholate (conventional amphotericin B). Newer agents have been developed to
      fulfill special niches and to compete with conventional amphotericin B by virtue
      of having more favourable toxicity profiles. Some agents have displaced
      conventional amphotericin B for the treatment of specific fungal diseases. For
      example, voriconazole has emerged as the preferred treatment for invasive
      pulmonary aspergillosis. This notwithstanding, conventional amphotericin B
      remains a useful agent for the treatment of paediatric fungal infections.
      Knowledge of the characteristics of the newer agents is important, given the
      increasing numbers of patients who are being treated with these drugs. Efforts
      need to be directed at research aimed at generating paediatric data where these
      are lacking. The antifungal agents herein described are most often used as
      monotherapy regimens because there is no uniform consensus on the value of
      combination therapy, except for specific scenarios.

PMID- 22132007
TI  - Identification and epidemiology of severe respiratory disease due to novel swine
      origin influenza A (H1N1) virus infection in Alberta.
AB  - BACKGROUND: In March 2009, global surveillance started detecting cases of
      influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were
      identified in the United States who were confirmed to be infected by a novel
      influenza A (H1N1) strain. The present article describes the first identified
      severe respiratory infection and the first death associated with pandemic H1N1
      (pH1N1) in Canada. METHODS: Enhanced public health and laboratory surveillance
      for pH1N1 was implemented throughout Alberta on April 24, 2009. Respiratory
      specimens from all patients with a respiratory illness and travel history or
      those presenting with a severe respiratory infection requiring hospitalization
      underwent screening for respiratory viruses using molecular methods. For the
      first severe case identified and the first death due to pH1N1, histocompatibility
      leukocyte antigens were compared by molecular methods. RESULTS: The first death
      (a 39-year-old woman) occurred on April 28, 2009, and on May 1, 2009, a 10-year
      old child presented with severe respiratory distress due to pH1N1. Both patients
      had no travel or contact with anyone who had travelled to Mexico; the cases were
      not linked. Histocompatibility antigen comparison of both patients did not
      identify any notable similarity. pH1N1 strains identified in Alberta did not
      differ from the Mexican strain. CONCLUSION: Rapid transmission of pH1N1 continued
      to occur in Alberta following the first death and the first severe respiratory
      infection in Canada, which were identified without any apparent connection to
      Mexico or the United States. Contact tracing follow-up suggested that oseltamivir
      may have prevented ongoing transmission of pH1N1.

PMID- 22132008
TI  - Radiographic Evaluation of Bone Formation and Density Changes after Mandibular
      Third Molar Extraction: A 6 Month Follow up.
AB  - BACKGROUND: There is a controversy about exact time of bone healing. The aim of
      this study was evaluation of bone formation and change of density after
      mandibular third molar extraction. METHODS: Radiographs were taken from 16 empty
      tooth sockets immediately after extraction of mandibular third molars and 2, 4
      and 6 months later under similar condition. The radiographs were digitized and
      the density numbers of pixels were calculated. Then, socket and neighbor regions
      were compared using Photoshop software. Three expert observers evaluated and
      compared the radiographs by the longitudinal radiographic assessment (LRA)
      method. Paired t-test and McNemar test were used to analyze the data and
      investigate the inter-observer reliability, respectively. RESULTS: Analysis of
      the quantitative digital subtraction radiography (QDSR) data indicated that the
      difference between the digital numbers of interest points and reference points
      has been decreased during the months 2, 4 and 6 but the difference between the
      month 4 and 6 was not significant. The alternative method indicated that the mean
      digital numbers in the socket within 0and 2 months period was less than 128 and
      within 4 and 6 months was more than 128. In evaluation of LRA method, lamina dura
      started to change gradually in month 2 and it might disappear completely after 6
      months. CONCLUSION: Both QDSR and LRA methods can be used in evaluation of the
      rate of bone formation in the tooth socket but the former is more precise.

PMID- 22132009
TI  - Effect of acidic agents on surface roughness of dental ceramics.
AB  - BACKGROUND: An increase in surface roughness of ceramics may decrease strength
      and affect the clinical success of ceramic restorations. However, little is known
      about the effect of acidic agents on ceramic restorations. The aim of this study
      was to evaluate the surface roughness of dental ceramics after being immersed in
      acidic agents. METHODS: Eighty-three ceramic disk specimens (12.0 mm in diameter
      and 2.0 mm in thickness) were made from four types of ceramics (VMK 95, Vitadur
      Alpha, IPS Empress Esthetic, and IPS e.max Ceram). Baseline data of surface
      roughness were recorded by profilometer. The specimens were then immersed in
      acidic agents (citrate buffer solution, pineapple juice and green mango juice)
      and deionized water (control) at 37 degrees C for 168 hours. One group was
      immersed in 4% acetic acid at 80 degrees C for 168 hours. After immersion,
      surface roughness was evaluated by a profilometer at intervals of 24, 96, and 168
      hours. Surface characteristics of specimens were studied using scanning electron
      microscopy (SEM). Data were analyzed using two-way repeated ANOVA and Tukey's
      multiple comparisons (alpha = 0.05). RESULTS: For all studied ceramics, all
      surface roughness parameters were significantly increased after 168 hours
      immersion in all acidic agents (P < 0.05). After 168 hours in 4% acetic acid,
      there were significant differences for all roughness parameters from other acidic
      agents of all evaluated ceramics. Among all studied ceramics, Vitadur Alpha
      showed significantly the greatest values of all surface roughness parameters
      after immersion in 4% acetic acid (P < 0.001). SEM photomicrographs also
      presented surface destruction of ceramics in varying degrees. CONCLUSION: Acidic
      agents used in this study negatively affected the surface of ceramic materials.
      This should be considered when restoring the eroded tooth with ceramic
      restorations in patients who have a high risk of erosive conditions.

PMID- 22132010
TI  - Effect of Postoperative Bleaching on Microleakage of Etch-and-Rinse and Self-etch
      Adhesives.
AB  - BACKGROUND: Bleaching the discoloured teeth may affect the tooth/composite
      interface. The aim of this in vitro experimental study was to evaluate the effect
      of vital tooth bleaching on microleakage of existent class V composite resin
      restorations bonded with three dental bonding agents. METHODS: Class V cavities
      were prepared on buccal surfaces of 72 intact, extracted human anterior teeth
      with gingival margins in dentin and occlusal margins in enamel, and randomly
      divided into 3 groups. Cavities in the three groups were treated with Scotch bond
      Multi-Purpose, a total etch system and Prompt L-Pop and iBond, two self-etch
      adhesives. All teeth were restored with Z250 resin composite material and thermo
      cycled. Each group was equally divided into the control and the bleached
      subgroups (n = 12). The bleached subgroups were bleached with 15% carbamide
      peroxide gel for 8 hours a day for 15 days. Microleakage scores were evaluated on
      the incisal and cervical walls. Data were analyzed using Kruskal-Wallis, Mann
      Whitney and Bonferroni post-hoc tests (alpha = 0.05). RESULTS: Bleaching with
      carbamide peroxide gel significantly increased the microleakage of composite
      restorations in Prompt L-Pop group at dentinal walls (P = 0.001). Bleaching had
      no effect on microleakage of restorations in the Scotch bond Multi-Purpose and
      iBond groups. CONCLUSION: Vital tooth bleaching with carbamide peroxide gel has
      an adverse effect on marginal seal of dentinal walls of existent composite resin
      restorations bonded with prompt L-Pop self-etch adhesive.

PMID- 22132011
TI  - Comparing the apical microleakage of lateral condensation and chloroform dip
      techniques with a new obturation method.
AB  - BACKGROUND: The final objective of root canal therapy is to create a hermetic
      seal along the length of the root canal system. For this purpose, many methods
      and materials have been introduced. The purpose of this study was to compare the
      apical microleakage in a new obturation technique (true-tug-back) with two other
      obturation techniques (lateral condensation and chloroform dip technique).
      METHODS: In this in vitro study 102 single canal teeth were selected. The crowns
      were removed, and the canals were prepared using step-back technique. The master
      apical file was K-file #40. The teeth were divided into 3 experimental groups of
      32 teeth. First group were obturated with lateral condensation technique and
      second group with chloroform dip technique and the third group with true-tug-back
      technique. Six teeth were used as control group. The teeth were placed in
      incubator at 100% humidity and 37 degrees c for three days. The roots of the
      teeth were coated with two layers of nail varnish except for the apical 2
      millimeter. Teeth were placed in Methylene blue 2% for one week. The teeth were
      sectioned vertically and the depth of maximum dye penetration for each tooth was
      recorded by stereomicroscope. Data were analyzed using ANOVA and Dunkan test.
      RESULTS: The mean liner dye penetration differences between lateral condensation
      group (6.88 +/- 4.06 mm) and chloroform dip technique group (7.16 +/- 3.37 mm)
      were not statistically significant (P = 0.719). The differences between true-tug
      back group (3.15 +/- 0.52 mm) and two other groups were statistically significant
      (P < 0.001). CONCLUSION: The results of this study showed that the true-tug-back
      technique can improve apical seal. Further studies are needed for this purpose.

PMID- 22132012
TI  - Comparative antibacterial efficacy of endemic satureja khuzistanica jamzad
      essential oil, sodium hypochlorite and chlorhexidine gluconate solutions as root
      canal irrigations.
AB  - BACKGROUND: The aim of this study was to compare the antibacterial efficacy of
      endemic Satureja Khuzistanica Jamzad (SKJ) essential oil as root canal irrigation
      versus 2.5% sodium hypochlorite and 2% chlorhexidine gluconate. METHODS: In
      current in vitro experimental study, fifty four single-rooted teeth were randomly
      divided into 6 groups of 9 samples: 2.5% sodium hypochlorite (NaOCl), 2%
      chlorhexidine gluconate (CHX), 0.31 mg/ml SKJ, 0.62 mg/ml SKJ, positive and
      negative controls. Each tooth was instrumented, sealed and autoclaved. Then, test
      groups were inoculated with E. faecalis, treated with irrigation solution and
      viable bacterial counts in intracanal dentin chips were determined. Utilizing
      SPSS 18 software, collected data were analyzed by Kruskal-Wallis one way analysis
      of variance (P = 0.05). RESULTS: 99.94 % and 99.50% reduction in bacteria load
      after 5 min treatment with NaOCl and CHX were detected, respectively. Similarly,
      99.97% and 99.96% reduction in bacterial counts were observed after 5 min
      application of 0.62 mg/ml and 0.31 mg/ml SKJ essential. No significant
      differences were detected among the four irrigation solutions (P = 0.755).
      CONCLUSION: SKJ essential oil with the minimum inhibitory concentration (MIC) of
      0.31 mg/ml could be an effective antibacterial irrigation solution.

PMID- 22132013
TI  - Comparison of Conventional and Standardized Bone Densitometry around Implants in
      Periapical Radiographs during a Three Months Period.
AB  - BACKGROUND: Comparing continuous films taken at different timescales is a way to
      study the alveolar bone changes around the implant over time. One of the
      important concerns in quantitative analysis of the alveolar bone changes over the
      time is to reduce variations in the X-ray imaging geometry and image density.
      METHODS: Using a modified XCP film holder together with the bite recording
      material, parallel periapical radiographs were taken from the implants placements
      of 16 patients in four steps. Densities of radiographs were measured in a
      conventional way using the video densitometry device. The same films were also
      scanned; sequential radiographic density of each patient was homogenised and the
      density was measured. Density changes obtained in both methods were compared. The
      data were evaluated using ANOVA, paired t-test and Pearson correlation (alpha =
      0.05). RESULTS: IN THE CONVENTIONAL METHOD OF DENSITOMETRY, THE AVERAGE DENSITIES
      WERE AS FOLLOWS: before operation 1.0044, after one week 0.9600, after one month
      0.9469 and after three months 0.9398. Also, in the standard method of
      densitometry, the average densities were as follows: before operation 111.7013,
      after one week 113.4225, after one month 119.4075 and after three months
      131.1162. Average density in conventional densitometry were not significantly
      different in various time stages (P = 0.395). But, the standard densitometry
      method showed a significant difference (P = 0.001). CONCLUSION: The average
      density obtained at different stages in the standard densitometry showed a
      gradual increase in the bone density in the entire process. Standardising the
      patient's consecutive radiographic images is essential for quantitative
      measurements over the time.

PMID- 22132014
TI  - Endo-perio dilemma: a brief review.
AB  - The actual relationship between periodontal and pulpal disease was first
      described by Simring and Goldberg in 1964. Since then, the term "perio-endo"
      lesion has been used to describe lesions due to inflammatory products found in
      varying degrees in both the periodontium and the pulpal tissues. The pulp and
      periodontium have embryonic, anatomic and functional inter-relationships. The
      simultaneous existence of pulpal problems and inflammatory periodontal disease
      can complicate diagnosis and treatment planning. A perio-endo lesion can have a
      varied pathogenesis which ranges from quite simple to relatively complex one.
      Knowledge of these disease processes is essential in coming to the correct
      diagnosis. This is achievable by careful history taking, examination and the use
      of special tests. The prognosis and treatment of each endodontic-periodontal
      disease type varies. Primary periodontal disease with secondary endodontic
      involvement and true combined endodontic-periodontal diseases require both
      endodontic and periodontal therapies. The prognosis of these cases depends on the
      severity of periodontal disease and the response to periodontal treatment. This
      enables the operator to construct a suitable treatment plan where unnecessary,
      prolonged or even detrimental treatment is avoided.

PMID- 22132015
TI  - Intraoral lipoma: report of 3 cases.
AB  - Lipoma, a benign tumor of adipose tissue is one of the most common benign
      neoplasms of the body. However, its occurrence in oral cavity is very rare. It
      accounts for 1 to 4% of benign neoplasms of mouth affecting predominantly the
      buccal mucosa, floor of mouth and tongue. We report three cases of intraoral
      lipoma, two in buccal mucosa and one in labial mucosa. An excisional biopsy was
      performed and histopathological examination revealed proliferation of mature
      adipocytes arranged in lobules and separated by fibrous septa. After 3 years
      follow up, the patients showed no signs of recurrence.

PMID- 22132006
TI  - Canadian clinical practice guidelines for invasive candidiasis in adults.
AB  - Candidemia and invasive candidiasis (C/IC) are life-threatening opportunistic
      infections that add excess morbidity, mortality and cost to the management of
      patients with a range of potentially curable underlying conditions. The
      Association of Medical Microbiology and Infectious Disease Canada developed
      evidence-based guidelines for the approach to the diagnosis and management of
      these infections in the ever-increasing population of at-risk adult patients in
      the health care system. Over the past few years, a new and broader understanding
      of the epidemiology and pathogenesis of C/IC has emerged and has been coupled
      with the availability of new antifungal agents and defined strategies for
      targeting groups at risk including, but not limited to, acute leukemia patients,
      hematopoietic stem cell transplants and solid organ transplants, and critical
      care unit patients. Accordingly, these guidelines have focused on patients at
      risk for C/IC, and on approaches of prevention, early therapy for suspected but
      unproven infection, and targeted therapy for probable and proven infection.

PMID- 22132016
TI  - Nevus of ota with buccal mucosal pigmentation: a rare case.
AB  - Nevus of Ota is a condition wherein the typical pattern of the bluish black
      pigmentation is noticed along with the cutaneous distribution of the trigeminal
      nerve. This condition is most prevalent in Japanese population but comparatively
      rare among Indians. We report a case of 23-year-old female presented with
      unilateral pigmented areas over the skin of forehead, malar area, ear and
      periorbital area. Blackish-blue pigmented areas were also noticed on the sclera.
      Brownish-black diffuse pigmented areas were also noticed on the buccal mucosa of
      the same side. The presence of pigmentation on the skin over pinna and oral
      pigmentation made our case a rare incidence. Oral pigmentations associated with
      nevus of Ota especially on the buccal mucosa have rarely been reported in the
      past.

PMID- 22132018
TI  - Solitary ring enhancing brain lesion in a patient with AIDS.
AB  - Toxoplasmosis in immune competent patients usually causes asymptomatic infection
      or mild symptoms, while in immunocompromised and AIDS patients it can be a life
      threatening condition. We report a case of cerebral toxoplasmosis in a patient
      with AIDS and review the causes of brain ring enhancing lesions.

PMID- 22132017
TI  - Oncologic Angiogenesis Imaging in the clinic---how and why.
AB  - The ability to control the growth of new blood vessels would be an extraordinary
      therapeutic tool for many disease processes. Too often, the promises of
      discoveries in the basic science arena fail to translate to clinical success.
      While several anti angiogenic therapeutics are now FDA approved, the envisioned
      clinical benefits have yet to be seen. The ability to clinically non-invasively
      image angiogenesis would potentially be used to identify patients who may benefit
      from anti-angiogenic treatments, prognostication/risk stratification and therapy
      monitoring. This article reviews the current and future prospects of implementing
      angiogenesis imaging in the clinic.

PMID- 22132019
TI  - Selenium and stereotypies in a mental health setting.
AB  - A 24-year-old man was referred with involuntary stereotypies of movement and
      thinking, of which he seemed unaware. On admission, comprehensive physical
      screening proved negative except for lowered selenium concentrations.
      Neuropsychological assessment revealed changes in performance on tests of
      attention, non-verbal reasoning and executive function consistent with his
      stereotypies. A review of his movements characterised them as possibly being
      consistent with non-paroxysmal kinesigenic dyskinesia. A low dose of sulpiride
      led to improvements in engagement and insight accompanied by modest reductions in
      movements.

PMID- 22132020
TI  - Recurrent mycobacterial infections in a patient with IL-12 deficiency.
AB  - This case of a middle aged woman with IL-12p40 deficiency and recurrent
      Mycobacterium kansasii infection demonstrates that in vitro sensitivities do not
      reliably predict the clinical response of non-tuberculous mycobacteria (NTMB),
      and emphasises the need to exercise caution when reducing treatment intensity in
      patients with type 1 cytokine defects on the basis of in vitro minimum inhibitory
      concentration (MIC) data alone.

PMID- 22132021
TI  - Diabetic ketoacidosis, respiratory distress and myocardial dysfunction.
AB  - This case report describes a patient with respiratory distress, myocardial
      dysfunction, elevated troponin level, ECG changes and pulmonary oedema secondary
      to new onset diabetic ketoacidosis (DKA). This case may be unique, but it is
      possible that less severe cases occur and are underappreciated in the paediatric
      setting. This report demonstrates the need to closely evaluate and monitor
      cardiac function in patients with DKA.

PMID- 22132022
TI  - Hypothyroidism presenting with recurrent pericardial tamponade.
AB  - We present a case of pericardial tamponade caused by hypothyroidism. A 66-year
      old man presented with acute chest pain radiating to the back. Computed
      tomography ruled out an aortic dissection but revealed a large pericardial
      effusion, which was confirmed on transthoracic echocardiography showing features
      of tamponade. The effusion was drained and subsequent thyroid function tests
      showed profound hypothyroidism. No other cause of the pericardial effusion could
      be identified. Despite the prompt initiation of levothyroxine (T4) replacement
      therapy, the effusion re-accumulated over a period of 10 days and required
      further drainage. Following that, aggressive thyroxine replacement therapy using
      liothyronine (T3) was initiated and there was no further re-accumulation.
      Hypothyroidism should be suspected in any cases of pericardial effusion where the
      cause is not obvious. We should be vigilant of re-accumulation, and T3
      replacement therapy should be considered in that situation.

PMID- 22132023
TI  - Lepromatous leprosy with erythema nodosum leprosum as immune reconstitution
      inflammatory syndrome in an HIV-1 infected patient after initiation of
      antiretroviral therapy.
AB  - We present the case of an HIV infected male patient with erythema nodosum
      leprosum and function loss of the peroneus nerve as manifestations of lepromatous
      leprosy. Since symptoms occurred after initiation of antiretroviral therapy and
      recovery of the immune system, the clinical picture is suggestive of a rare form
      of an immune reconstitution inflammatory syndrome.

PMID- 22132024
TI  - True posterior tibial artery aneurysm in a young patient: surgical or
      endovascular treatment?
AB  - Aneurysms of tibial arteries are extremely rare. Here we report a case of a true
      posterior tibial artery aneurysm in a young patient without any associated
      pathology and discuss surgical and endovascular treatment. A young Caucasian male
      was admitted to our department for painful and pulsatile swelling of the right
      calf. Colour Doppler ultrasound scan visualised an aneurysmal dilation of the
      posterior tibial artery. The patient had no trauma to the area and denied other
      history of vascular disease. Angio-CT and angio-magnetic resonance imaging showed
      a larger aneurysm compared to ultrasound scan. We performed an embolisation of
      the aneurysm because of the risk of rupture, as distal collateral circulation
      ensured foot vascularisation. Endovascular treatment of aneurysms of small
      arteries seems to be a safe therapeutic and non-invasive choice, particularly in
      young patients in whom the presence of collaterals guarantees distal
      vascularisation.

PMID- 22132025
TI  - Compartment syndrome after low molecular weight heparin following lower limb
      blunt trauma: lessons for outpatient deep vein thrombosis protocols.
AB  - A fit and well 36-year-old male presented to his general practitioner with a 10
      day history of pain and swelling in his right leg following a football injury. He
      had sustained blunt trauma to the lateral aspect of his right thigh and described
      it as a "dead leg". A clinical diagnosis of deep vein thrombosis (DVT) was made
      and the patient was advised to attend the DVT outpatient clinic. In line with
      hospital protocol, he was commenced on low molecular weight heparin (LMWH
      enoxaparin) as an outpatient pending urgent ultrasound scan. Following his second
      dose of enoxaparin, he developed worsening pain in his thigh and was admitted for
      urgent ultrasound scan which showed a large haematoma (15/5 cm) in the thigh
      (figure 1). A diagnosis of acute compartment syndrome was made and the patient
      was taken to theatre for an emergency right thigh fasciotomy and decompression of
      the haematoma.

PMID- 22132026
TI  - Retrograde popliteal approach to common femoral vein stenosis in an intravenous
      drug user with hostile groin: a case report.
AB  - Intravenous (IV) drug abuse is a common problem in our society. One complication
      of this practice is venous stenosis, endovascular management of which can be
      technically challenging especially in patients with a hostile groin. We describe
      an ipsilateral retrograde popliteal approach in a 26-year-old IV drug user
      presenting with swelling of the left leg secondary to common femoral vein
      stenosis. This approach represents the next best method following failed
      contralateral/cross-bifurcation access and is a safe, convenient alternative
      offering a "straight run" at the lesion.

PMID- 22132027
TI  - Identifying the aetiology of left ventricular hypertrophy in an athlete:
      importance of lifestyle modification.
AB  - The aetiology of left ventricular hypertrophy (LVH) in an athlete is often
      difficult to identify. We describe a 29-year-old fitness instructor who was
      referred for investigation of syncope. He gave a history of intensive weight
      lifting and anabolic steroid use at supra-therapeutic doses for the preceding 6
      years. Electrocardiography showed inferolateral repolarisation abnormalities and
      a transthoracic echocardiogram demonstrated asymmetrical LVH with reduced left
      ventricular cavity dimensions. There was no left ventricular outflow tract
      obstruction or systolic motion of the anterior mitral valve leaflet. These
      findings were confirmed on cardiac magnetic resonance imaging (CMR). The
      differential diagnosis included athlete's heart, steroid-induced cardiomyopathy
      and non-obstructive hypertrophic cardiomyopathy. The patient was advised to
      discontinue both steroid use and intensive training. After 3 years of steroid
      abstinence but continued training, the syncopal episodes and the ECG
      abnormalities completely resolved, associated with regression of LVH on
      echocardiography and CMR.

PMID- 22132028
TI  - Preliminary experience with the combined use of recombinant bone morphogenetic
      protein and bisphosphonates in the treatment of congenital pseudarthrosis of the
      tibia.
AB  - PURPOSE: Congenital pseudarthrosis of the tibia (CPT) is a rare but serious
      disorder in children. No single approach has clearly emerged as superior in terms
      of operative procedure, fixation, optimal time for surgery or adjunctive
      pharmaceutical intervention. CPT is frequently associated with neurofibromatosis
      type 1 (NF1), a condition featuring deficient bone anabolism and excessive
      catabolism. We have therefore combined the use of bone morphogenetic proteins
      (BMP) with bisphosphonates (BP) as an adjunct to surgical intervention. METHODS:
      Between 2002 and 2008 we administered BMP-7 (OP-1) at the time of surgery
      followed by BP (pamidronate or zoledronic acid) in eight Crawford type IV CPT
      cases in seven patients (six with a confirmed diagnosis of NF1) with a median age
      of 7 years (range 2 years 11 months to 12 years) at surgery. RESULTS: In six of
      eight cases, this approach led to primary healing after a mean of 5.5 months
      (range 4-7 months). One of these cases represented 17 months after primary
      healing of a proximal CPT with a new further distal fracture that required
      multiple operations to finally unite at 19 months. The two remaining cases
      ultimately reached union after multiple operations at 14 and 30 months,
      respectively, but required recent treatment for refractures. CONCLUSION: Based on
      these clinical data (primary healing in 6/8 cases) and prior pre-clinical
      findings, we propose that BP therapy may be helpful in preserving the BMP-induced
      bone formation by inhibiting the osteoclastic bone loss. Key factors to achieve
      union in CPT include sufficient fixation, meticulous resection of the dysplastic
      tissue and the establishment of a net anabolic environment for bone healing.
      Whether our biological concept of balancing the anabolic and catabolic responses
      with BMP and BP improves healing rates in the complex treatment of NF1 CPT
      remains uncertain and warrants larger prospective multicentre trials.

PMID- 22132029
TI  - Outcome of limb lengthening in fibular hemimelia and a functional foot.
AB  - BACKGROUND: The decision to recommend either reconstructive or ablative surgery
      to the parents of children with fibular hemimelia is difficult and debatable in
      the orthopaedic literature. METHODS: This is a retrospective study reporting our
      experience of the treatment of eight children (eight limbs) with fibular
      hemimelia with limb lengthening using Ilizarov or Taylor spatial frames. All of
      these children had type 1 or 2a fibular hemimelia (Achterman and Kalamchi). We
      used the number of rays present in the foot as a guide to decide on the treatment
      option. Children with more than three rays at the time of presentation were
      considered for limb reconstruction using Taylor spatial or Ilizarov frames.
      RESULTS: All patients were ambulatory and mobile with acceptable leg lengths and
      limb alignment at the time of last follow-up. All of them were satisfied with the
      outcome. Knee stiffness was a significant problem in the majority of the patients
      following lengthening. CONCLUSIONS: We conclude that limb reconstruction in
      children with less severe forms of fibular hemimelia is a good option.

PMID- 22132030
TI  - Bifid thumb type IV in children: transferring an epiphyseal segment of the
      proximal phalanx with insertion of the abductor pollicis brevis tendon.
AB  - OBJECTIVE: To evaluate the clinical and functional results of the surgical
      treatment of bifid thumb type IV in children. MATERIALS AND METHODS: A
      retrospective study was undertaken from January 1995 to December 2006. Clinical
      and radiographic evaluations were made according to Wassel's classification. The
      patients were performed by transferring an epiphyseal segment of the proximal
      phalanx with insertion of the abductor pollicis brevis tendon into the radial
      side of the epiphyseal proximal phalanx of the ulnar thumb. All patients were
      operated using one of five surgical procedures for bicephalous metacarpus,
      cartilaginous connection between the radial and ulnar proximal phalanges, the
      angular deformity of the metacarpophalangeal joint (MPJ) is >20 degrees , and
      zigzag deformities. The postoperative results of the patients were evaluated for
      both function and cosmesis according to Tien's modified Tada scoring system.
      RESULTS: One hundred and sixty-four patients (102 females, 62 males) were
      included in this study. The MPJ was stable in 170 thumbs, 15 thumbs had 10
      degrees  of radial instability, and new collateral ligaments were augmented in 27
      thumbs. The alignment was normal in 75 thumbs, with alignment of the
      interphalangeal joint (IPJ) in 101 thumbs and alignment of the MPJ in 75 thumbs.
      Postoperatively, there were zigzag deformities in four thumbs (developed zigzag
      in two thumbs, recurrent zigzag in two thumbs); there was no first web space in
      those hands. There were four of 185 thumbs with thumb stiffness. The abductor
      function of 185 thumbs was as follows: >70 degrees  in 158 thumbs (85.4%), 50
      degrees -70 degrees  in 21 thumbs (11.4%), and <50 degrees  in six thumbs (3.2%).
      At the latest follow-up evaluation, no evidence of physeal growth injury or
      growth arrest was observed in any patient. Overall, we attained good results in
      140 thumbs (75.7%), fair results in 36 thumbs (19.4%), and poor results in nine
      thumbs (4.9%). CONCLUSION: We recommend the use of an epiphyseal segment of the
      proximal phalanx with insertion of the abductor pollicis brevis tendon into the
      radial side of the epiphyseal proximal phalanx of the ulnar thumb and to restore
      anatomical insertion of the abductor pollicis brevis muscle. The technique is
      simple, safe, and effective for thumb abductor function in the treatment of bifid
      thumb type IV in children.

PMID- 22132031
TI  - Obscure pathology of pulled elbow: dynamic high-resolution ultrasound-assisted
      classification.
AB  - AIM: Pulled elbow or nursemaid's elbow is a radial head subluxation caused by a
      sudden pull on the extended pronated forearm. Children with pulled elbow usually
      respond dramatically for reduction, yet others show delayed improvement with no
      clear pathologic explanation. The aim of our study is to propose an explanation
      for the varying clinical response after the reduction of pulled elbow aided by
      ultrasound classification of the underlying pathology and its impact on
      management. PATIENTS AND METHODS: Fifty children with a mean age of 3.8 +/- 1.1
      (standard deviation [SD]) years with pulled elbow were scanned by static and
      dynamic ultrasound utilizing the other elbow as the standard. The radial annular
      ligament (RAL) was examined for integrity and interposition, with measurement of
      the radiocapitellar distance. Reduction was performed following the
      hyperpronation technique, and postreduction splinting was guided by ultrasound
      findings. Postreduction scans and 1-year follow up were performed. RESULTS: Of
      the 50 included children, 39 (78%) had intact, yet interposed annular ligament
      (classified as type I) and 11 (22%) had torn annular ligament (classified as type
      II). The latter underwent splinting for 7 days. Three out of the 50 children had
      recurrent subluxation and constituted false-negative cases for the detection of
      torn ligament and represented the reoccurrence rate of 6%. The sensitivity,
      specificity, and accuracy for the ultrasound diagnosis of torn RAL were 76.9,
      92.3, and 92%, respectively. CONCLUSION: PULLED ELBOW IS CLASSIFIED AS FOLLOWS:
      type I, with an interposed RAL, and type II, with torn ligament.

PMID- 22132032
TI  - The diagnostic value of the facial features of Marfan syndrome.
AB  - PURPOSE: We examined the prevalence of known facial features of Marfan syndrome
      (MFS)-dolicocephaly, malar hypoplasia, enophthalmos, retrognathia, and down
      slanting palpebral fissures-and the diagnostic utility (sensitivity, specificity,
      accuracy, predictive values, and likelihood ratios) of using them for screening
      and diagnosis. METHODS: Frontal and lateral photographs of 76 subjects with MFS
      (average age 18.3 years) and of 76 age- and gender-matched controls were
      obtained, randomized, and compiled into an online survey. Three physicians
      experienced with MFS rated each photograph for the presence of each feature and
      indicated whether each photograph triggered a suspicion for MFS. Eight non-expert
      orthopaedic surgeons reviewed a subset of those photographs and indicated if each
      triggered a suspicion for MFS. Half of the non-experts then received a brief
      diagnosis instructional sheet, and all non-experts were retested. The results
      were compared using Chi-square tests and t-tests with a significance level of P <
      0.05. RESULTS: Using facial features alone, the accuracy of experienced
      physicians in identifying individuals with MFS was 73%. Facial features had a 54%
      sensitivity, a 91% specificity, an 86% positive predictive value (PPV), a 67%
      negative predictive value (NPV), a 6.9% positive likelihood ratio (PLR), and a
      50% negative likelihood ratio (NLR) for MFS. There was no significant difference
      in the diagnostic accuracy between non-experts receiving and not receiving
      instructions. CONCLUSIONS: Facial features are more specific than sensitive for
      MFS. Therefore, the recognition of facial features of MFS can be used as an
      initial screening tool, but facial features do not have a high sensitivity for
      MFS.

PMID- 22132033
TI  - Preliminary evaluation of implementing the Ponseti method for correction of
      clubfoot in Vietnam.
AB  - PURPOSE: To evaluate the short-term results of the non-surgical Ponseti method
      training programs run in Ho Chinh Minh City, Vietnam. METHODS: A questionnaire
      was developed and distributed to the 57 trainees who had completed one of the 3
      day training courses. RESULTS: Of the 57 questionnaires distributed, 36 (63%)
      were completed and returned for evaluation. Most responders were continuing to
      use the Ponseti method for management of clubfoot. On average, each trainee had
      treated 16 babies with clubfoot, most of whom were less than 12 months of age,
      within 2 years of the initial training course and were achieving good clinical
      correction. The major problems identified were the inability to perform an
      Achilles tenotomy, lack of availability of the foot abduction splint, and parent
      compliance. The course materials were being used for reference and for
      dissemination of the Ponseti method to other clinical peers. CONCLUSIONS:
      Evaluation of the Ponseti method training program for management of clubfoot in
      Vietnam revealed continued use of the technique at 12-24 months post-training. A
      longer term and more objective assessment of the babies/children treated and of
      the associated gait function and foot comfort would be beneficial.

PMID- 22132034
TI  - Modified Chrisman-Snook repair for the treatment of chronic ankle ligamentous
      instability in children and adolescents.
AB  - PURPOSE: Chronic ankle ligamentous instability is not uncommonly encountered in
      children and adolescents. A number of operative procedures have been developed
      and described in the literature, including variations on the original Chrisman
      Snook (CS) repair. The purpose of this study is to describe a modification of the
      CS repair and report the outcomes of this surgery for the treatment of chronic
      ankle ligamentous instability in children and adolescents. METHODS: A
      retrospective review was conducted of 100 consecutive surgeries in 66 children
      performed by a single surgeon who modified the CS repair using a split peroneus
      brevis tendon to reinforce the anterior talofibular and calcaneofibular ligaments
      in chronic ligamentously lax patients. All charts were reviewed for
      complications. Fifty-three cases had at least a 2-year follow-up and were
      evaluated for the following outcomes: return to activity, ligamentous laxity,
      pain, and subsequent sprains. RESULTS: Of the 100 surgeries performed, no patient
      required repeat ligamentous repair. There were no deep wound infections. There
      were 10 cases of minor wound healing problems and two cases of temporary nerve
      dysfunction, one of which resolved without surgical intervention and the other is
      resolving with no plans for surgical intervention. There were two cases of sural
      nerve branch entrapment which required subsequent surgery due to neuroma
      formation. Of the 53 cases with at least a 2-year follow-up, the following
      outcomes were obtained: all patients returned to full activities of their choice;
      all but one case maintained <=45 degrees  of ankle inversion postoperatively; all
      patients were pain free or had only occasional discomfort; and 23% of the ankles
      experienced subsequent minor sprains, but all were minor and resolved without
      consequence. CONCLUSIONS: A modification of the CS repair where the split
      peroneus brevis tendon is used to create ankle stability has been routinely
      successful in 100 consecutive cases of chronic ligamentous instability in
      children and adolescents with very few complications.

PMID- 22132035
TI  - Malunion following flexible intramedullary nails for tibial and femoral fractures
      in adolescents.
AB  - PURPOSE: Flexible intramedullary nails (FIN) are increasingly used in the
      management of paediatric tibial and femoral fractures. Concerns have recently
      been raised regarding the use of FIN in older children. The aim of this study was
      to determine how effective FIN is in treating tibial and femoral fractures in
      adolescents. METHODS: Patients aged 11 years or older undergoing FIN for tibial
      and femoral fractures between 2003 and 2009 were identified. Radiographs and case
      notes were reviewed to identify complications. RESULTS: Thirty-five consecutive
      adolescent patients underwent FIN for tibial (n = 21) and femoral fractures (n =
      15), with a mean age of 12.9 years. The mean radiographic follow up was 29 weeks.
      Sixty percent (60%, n = 9) and 38% (n = 9) of femoral and tibial fractures,
      respectively, malunited. Fracture severity was associated with increased malunion
      for both tibial and femoral fractures (P = 0.046 and P = 0.044, respectively).
      Two femoral fractures took longer than 20 weeks to unite and seven tibial
      fractures took longer than 16 weeks to unite. CONCLUSION: The higher than
      expected rates of malunion and delayed union in this study suggest that other
      treatments should be considered when treating adolescents with unstable tibial or
      femoral fractures.

PMID- 22132036
TI  - Normal development of the knee angle in healthy Indian children: a clinical study
      of 215 children.
AB  - PURPOSE: Physicians should be aware of the physiological variations of the knee
      angle in the local population to avoid unnecessary intervention in normal
      children. The normal development of the knee angle in children has been studied
      in various ethnic groups. However, there is a scarcity of such literature for
      Indian children. METHODS: Using clinical methods, the tibiofemoral angles (TFAs)
      were measured in 215 healthy Indian children ranging from 2 to 15 years of age. A
      record of the intermalleolar distance (IMD) and intercondylar distance (ICD) was
      also kept of all of the subjects. RESULTS: We found that physiological varus
      rarely persists beyond 2 years of age in Indian children. A progressive increase
      in knee valgus occurs after 2 years of age, with peak knee valgus averaging
      almost 8 degrees  at around 6 years of age. Thereafter, the valgus at the knee
      decreases and, after the age of 10 years, stabilizes to around 4-5 degrees  in
      most of the children. Indian girls show, overall, more valgus alignment of the
      knees as compared to boys. CONCLUSIONS: The overall pattern of development might
      be slightly different in Indian children, especially in Indian girls, with early
      reversal of physiological varus (<2 years of age) and a late peak of maximal
      valgus at the knee (6 years of age). Varus after 3 years seems atypical for
      Indian children. We provide an elaborate set of data for the mean TFA of
      different age groups and believe that this data could be of potential benefit to
      the physicians while evaluating lower limb alignment in Indian children aged 2-15
      years.

PMID- 22132037
TI  - Improving Clinical Trial Participant Tracking Tools Using Knowledge-anchored
      Design Methodologies.
AB  - OBJECTIVE: Rigorous human-computer interaction (HCI) design methodologies have
      not traditionally been applied to the development of clinical trial participant
      tracking (CTPT) tools. Given the frequent us of iconic HCI models in CTPTs, and
      prior evidence of usability problems associated with the use of ambiguous icons
      in complex interfaces, such approaches may be problematic. Presentation Discovery
      (PD), a knowledge-anchored HCI design method, has been previously demonstrated to
      improve the design of iconic HCI models. In this study, we compare the usability
      of a CTPT HCI model designed using PD and an intuitively designed CTPT HCI model.
      METHODS: An iconic CPTP HCI model was created using PD. The PD-generated and an
      existing iconic CTPT HCI model were subjected to usability testing, with an
      emphasis on task accuracy and completion times. Study participants also completed
      a qualitative survey instrument to evaluate subjective satisfaction with the two
      models.  RESULTS: CTPT end-users reliably and reproducibly agreed on the visual
      manifestation and semantics of prototype graphics generated using PD. The
      performance of the PD-generated iconic HCI model was equivalent to an existing
      HCI model for tasks at multiple levels of complexity, and in some cases superior.
      This difference was particularly notable when tasks required an understanding of
      the semantic meanings of multiple icons.  CONCLUSION: The use of PD to design an
      iconic CTPT HCI model generated beneficial results and improved end-user
      subjective satisfaction, while reducing task completion time. Such results are
      desirable in information and time intensive domains, such as clinical trials
      management.

PMID- 22132038
TI  - Sensory evoked and event related oscillations in Alzheimer's disease: a short
      review.
AB  - Diagnosis and treatment of Alzheimer's disease (AD) depend on clinical evaluation
      and there is a strong need for an objective tool as a biomarker. Our group has
      investigated brain oscillatory responses in a small group of AD subjects. We
      found that the de novo (untreated) AD group differs from both the cholinergically
      treated AD group and aged-matched healthy controls in theta and delta responses
      over left frontal-central areas after cognitive stimulation. On the contrary, the
      difference observed in AD groups upon a sensory visual stimulation includes
      response increase over primary or secondary visual sensorial areas compared to
      controls. These findings imply at least two different neural networks, depending
      on type of stimulation (i.e. cognitive or sensory). The default mode defined as
      activity in resting state in AD seems to be affected electrophysiologically.
      Coherences are also very valuable in observing the group differences, especially
      when a cognitive stimulus is applied. In healthy controls, higher coherence
      values are elicited after a cognitive stimulus than after a sensory task. Our
      findings support the notion of disconnectivity of cortico-cortical connections in
      AD. The differences in comparison of oscillatory responses upon sensory and
      cognitive stimulations and their role as a biomarker in AD await further
      investigation in series with a greater number of subjects.

PMID- 22132040
TI  - Functional model of biological neural networks.
AB  - A functional model of biological neural networks, called temporal hierarchical
      probabilistic associative memory (THPAM), is proposed in this paper. THPAM
      comprises functional models of dendritic trees for encoding inputs to neurons, a
      first type of neuron for generating spike trains, a second type of neuron for
      generating graded signals to modulate neurons of the first type, supervised and
      unsupervised Hebbian learning mechanisms for easy learning and retrieving, an
      arrangement of dendritic trees for maximizing generalization, hardwiring for
      rotation-translation-scaling invariance, and feedback connections with different
      delay durations for neurons to make full use of present and past informations
      generated by neurons in the same and higher layers. These functional models and
      their processing operations have many functions of biological neural networks
      that have not been achieved by other models in the open literature and provide
      logically coherent answers to many long-standing neuroscientific questions.
      However, biological justifications of these functional models and their
      processing operations are required for THPAM to qualify as a macroscopic model
      (or low-order approximate) of biological neural networks.

PMID- 22132039
TI  - Spontaneous brain activity observed with functional magnetic resonance imaging as
      a potential biomarker in neuropsychiatric disorders.
AB  - As functional magnetic resonance imaging (fMRI) studies have yielded increasing
      amounts of information about the brain's spontaneous activity, they have revealed
      fMRI's potential to locate changes in brain hemodynamics that are associated with
      neuropsychiatric disorders. In this paper, we review studies that support the
      notion that changes in brain spontaneous activity observed by fMRI can be used as
      potential biomarkers for diagnosis and treatment evaluation in neuropsychiatric
      disorders. We first review the methods used to study spontaneous activity from
      the perspectives of (1) the properties of local spontaneous activity, (2) the
      spatial pattern of spontaneous activity, and (3) the topological properties of
      brain networks. We also summarize the major findings associated with major
      neuropsychiatric disorders obtained using these methods. Then we review the pilot
      studies that have used spontaneous activity to discriminate patients from normal
      controls. Finally, we discuss current challenges and potential research
      directions to further elucidate the clinical use of spontaneous brain activity in
      neuropsychiatric disorders.

PMID- 22132041
TI  - A Kalman filtering approach to the representation of kinematic quantities by the
      hippocampal-entorhinal complex.
AB  - Several regions of the brain which represent kinematic quantities are grouped
      under a single state-estimator framework. A theoretic effort is made to predict
      the activity of each cell population as a function of time using a simple state
      estimator (the Kalman filter). Three brain regions are considered in detail: the
      parietal cortex (reaching cells), the hippocampus (place cells and head-direction
      cells), and the entorhinal cortex (grid cells). For the reaching cell and place
      cell examples, we compute the perceived probability distributions of objects in
      the environment as a function of the observations. For the grid cell example, we
      show that the elastic behavior of the grids observed in experiments arises
      naturally from the Kalman filter. To our knowledge, the application of a tensor
      Kalman filter to grid cells is completely novel.

PMID- 22132042
TI  - Neural coding properties based on spike timing and pattern correlation of retinal
      ganglion cells.
AB  - Correlation between spike trains or neurons sometimes indicates certain neural
      coding rules in the visual system. In this paper, the relationship between spike
      timing correlation and pattern correlation is discussed, and their ability to
      represent stimulus features is compared to examine their coding strategies not
      only in individual neurons but also in population. Two kinds of stimuli, natural
      movies and checkerboard, are used to arouse firing activities in chicken retinal
      ganglion cells. The spike timing correlation and pattern correlation are
      calculated by cross-correlation function and Lempel-Ziv distance respectively.
      According to the correlation values, it is demonstrated that spike trains with
      similar spike patterns are not necessarily concerted in firing time. Moreover,
      spike pattern correlation values between individual neurons' responses reflect
      the difference of natural movies and checkerboard; neurons cooperate with each
      other with higher pattern correlation values which represent spatiotemporal
      correlations during response to natural movies. Spike timing does not reflect
      stimulus features as obvious as spike patterns, caused by their particular coding
      properties or physiological foundation. As a result, separating the pattern
      correlation out of traditional timing correlation concept uncover additional
      insight in neural coding.

PMID- 22132043
TI  - Robust stability analysis of delayed Takagi-Sugeno fuzzy Hopfield neural networks
      with discontinuous activation functions.
AB  - In this paper, the global robust stability problem of delayed Takagi-Sugeno fuzzy
      Hopfield neural networks with discontinuous activation functions (TSFHNNs) is
      considered. Based on Lyapunov stability theory and M-matrices theory, we derive a
      stability criterion to guarantee the global robust stability of TSFHNNs. Compared
      with the existing literature, we remove the assumptions on the neuron activations
      such as Lipschitz conditions, bounded, monotonic increasing property or the
      assumption that the right-limit value is bigger than the left one at the
      discontinuous point. Finally, two numerical examples are given to show the
      effectiveness of the proposed stability results.

PMID- 22132044
TI  - Generalized optimal spatial filtering using a kernel approach with application to
      EEG classification.
AB  - Common spatial patterns (CSP) has been widely used for finding the linear spatial
      filters which are able to extract the discriminative brain activities between two
      different mental tasks. However, the CSP is difficult to capture the nonlinearly
      clustered structure from the non-stationary EEG signals. To relax the presumption
      of strictly linear patterns in the CSP, in this paper, a generalized CSP (GCSP)
      based on generalized singular value decomposition (GSVD) and kernel method is
      proposed. Our method is able to find the nonlinear spatial filters which are
      formulated in the feature space defined by a nonlinear mapping through kernel
      functions. Furthermore, in order to overcome the overfitting problem, the
      regularized GCSP is developed by adding the regularized parameters. The
      experimental results demonstrate that our method is an effective nonlinear
      spatial filtering method.

PMID- 22132045
TI  - The modeling and simulation of visuospatial working memory.
AB  - Camperi and Wang (Comput Neurosci 5:383-405, 1998) presented a network model for
      working memory that combines intrinsic cellular bistability with the recurrent
      network architecture of the neocortex. While Fall and Rinzel (Comput Neurosci
      20:97-107, 2006) replaced this intrinsic bistability with a biological mechanism
      Ca(2+) release subsystem. In this study, we aim to further expand the above work.
      We integrate the traditional firing-rate network with Ca(2+) subsystem-induced
      bistability, amend the synaptic weights and suggest that Ca(2+) concentration
      only increase the efficacy of synaptic input but has nothing to do with the
      external input for the transient cue. We found that our network model maintained
      the persistent activity in response to a brief transient stimulus like that of
      the previous two models and the working memory performance was resistant to noise
      and distraction stimulus if Ca(2+) subsystem was tuned to be bistable.

PMID- 22132046
TI  - Short term memory bowing effect is consistent with presentation rate dependent
      decay.
AB  - I reanalyze the free recall data of Murdock, J Exp Psychol 64(5):482-488 (1962)
      and Murdock and Okada, J Verbal Learn and Verbal Behav 86:263-267 (1970) which
      show the famous bowing effect in which initial and recent items are recalled
      better than intermediate items (primacy and recency effects). Recent item recall
      probabilities follow a logarithmic decay with time of recall consistent with the
      tagging/retagging theory. The slope of the decay increases with increasing
      presentation rate. The initial items, with an effectively low presentation rate,
      decay with the slowest logarithmic slope, explaining the primacy effect. The
      finding that presentation rate limits the duration of short term memory suggests
      a basis for memory loss in busy adults, for the importance of slow music
      practice, for long term memory deficiencies for people with attention deficits
      who may be artificially increasing the presentation rates of their surroundings.
      A well-defined, quantitative measure of the primacy effect is introduced.

PMID- 22132047
TI  - There is no capacity limited buffer in the Murdock (1962) free recall data.
AB  - Theories of short term memory often include a limited capacity "buffer". Such a
      buffer contains items which do not decay at all but are overwritten by new data.
      I show that one of the experiments that fueled the buffer concept, the free
      recall experiments by Murdock (J Exp Psychol 64(5):482-488, 1962), does not
      contain such a buffer.

PMID- 22132048
TI  - Cloud brain: a postulate: Letter to the Editor.

PMID- 22132049
TI  - Building momentum for systems and synthetic biology in India.
AB  - Biological systems are inherently noisy. Predicting the outcome of a perturbation
      is extremely challenging. Traditional reductionist approach of describing
      properties of parts, vis-a-vis higher level behaviour has led to enormous
      understanding of fundamental molecular level biology. This approach typically
      consists of converting genes into junk (knock-down) and garbage (knock-out) and
      observe how a system responds. To enable broader understanding of biological
      dynamics, an integrated computational and experimental strategy was formally
      proposed in mid 1990s leading to the re-emergence of Systems Biology. However,
      soon it became clear that natural systems were far more complex than expected. A
      new strategy to address biological complexity was proposed at MIT (Massachusetts
      Institute of Technology) in June 2004, when the first meeting of synthetic
      biology was held. Though the term 'synthetic biology' was proposed during 1970s
      (Szybalski in Control of gene expression, Plenum Press, New York, 1974), the
      usage of the original concept found an experimental proof in 2000 with the
      demonstration of a three-gene circuit called repressilator (Elowitz and Leibler
      in Nature, 403:335-338, 2000). This encouraged people to think of forward
      engineering biology from a set of well described parts.

PMID- 22132050
TI  - Intellectual property rights in synthetic biology: an anti-thesis to open access
      to research?
AB  - Synthetic Biology is a surging area of contemporary life science based research
      that is rapidly evolving by virtue of its multidisciplinary composition and
      applications. Biology never before has seen such a gold rush and demonstrated
      potential for knowledge based economy. The area of synthetic biology is in a
      nascent and tender stage, however issues pertaining to open access to research
      versus the monopolistic intellectual property regime (specifically patents) have
      already started raising concerns in the emerging bio-based economy. The present
      study critically analyses the comparative benefits as well as lacunas of open
      access to research and patenting issues. It is noteworthy that both approaches
      for synthetic biology development have to co-exist in order to optimally benefit
      the society at large.

PMID- 22132051
TI  - Creating novel protein scripts beyond natural alphabets.
AB  - Natural proteins are concatenated amino acids with definite handedness or
      chirality, with their spatial orientation being preferentially left handed or L
      chiral. This paper discusses the biophysics of stereo-chemical perturbation to
      proteins using D-(alpha) amino acid and its utility as an additional design
      alphabet while scripting novel protein structures.

PMID- 22132052
TI  - Design of a novel nucleoside analog as potent inhibitor of the NAD dependent
      deacetylase, SIRT2.
AB  - Sirtuins (class III histone deacetylase) are evolutionarily conserved NAD(+)
      dependent enzymes that catalyze the deacetylation of acetyl-lysine residues of
      histones and other target proteins. Because of their associations in various
      pathophysiological conditions, the identification of small molecule modulators
      has been of significant interest. In the present study, virtual screening was
      carried out with NCI Diversity Set II using crystal structure of hSIRT2 (PDB ID:
      1J8F) as a model for the docking procedure to find potential compounds, which
      were then subjected to experimental tests for their in vitro SIRT2 inhibitory
      activity. One of the 40 compounds tested, NSC671136 (IUPAC name: 6-Acetyl-4-oxo
      1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl 2,4
      dichlorobenzoate) has structurally unique scaffold, showed strong inhibitory
      activity towards SIRT2 with IC(50) of ~8.7 MUM and to a lesser extent on SIRT1
      activity. The reported compound is substantially potent compared to the published
      SIRT2 inhibitors and serves as an excellent base for future lead development.

PMID- 22132053
TI  - Programming languages for synthetic biology.
AB  - In the backdrop of accelerated efforts for creating synthetic organisms, the
      nature and scope of an ideal programming language for scripting synthetic
      organism in-silico has been receiving increasing attention. A few programming
      languages for synthetic biology capable of defining, constructing, networking,
      editing and delivering genome scale models of cellular processes have been
      recently attempted. All these represent important points in a spectrum of
      possibilities. This paper introduces Kera, a state of the art programming
      language for synthetic biology which is arguably ahead of similar languages or
      tools such as GEC, Antimony and GenoCAD. Kera is a full-fledged object oriented
      programming language which is tempered by biopart rule library named Samhita
      which captures the knowledge regarding the interaction of genome components and
      catalytic molecules. Prominent feature of the language are demonstrated through a
      toy example and the road map for the future development of Kera is also
      presented.

PMID- 22132054
TI  - Sequence signatures of allosteric proteins towards rational design.
AB  - Allostery is the phenomenon of changes in the structure and activity of proteins
      that appear as a consequence of ligand binding at sites other than the active
      site. Studying mechanistic basis of allostery leading to protein design with
      predetermined functional endpoints is an important unmet need of synthetic
      biology. Here, we screened the amino acid sequence landscape in search of
      sequence-signatures of allostery using Recurrence Quantitative Analysis (RQA)
      method. A characteristic vector, comprised of 10 features extracted from RQA was
      defined for amino acid sequences. Using Principal Component Analysis, four
      factors were found to be important determinants of allosteric behavior. Our
      sequence-based predictor method shows 82.6% accuracy, 85.7% sensitivity and 77.9%
      specificity with the current dataset. Further, we show that Laminarity-Mean
      hydrophobicity representing repeated hydrophobic patches is the most crucial
      indicator of allostery. To our best knowledge this is the first report that
      describes sequence determinants of allostery based on hydrophobicity. As an
      outcome of these findings, we plan to explore possibility of inducing allostery
      in proteins.

PMID- 22132055
TI  - Phenotypic characterization of Corynebacterium glutamicum using elementary modes
      towards synthesis of amino acids.
AB  - Elementary flux mode (EFM) analysis is a powerful tool to represent the metabolic
      network structure and can be further utilized for flux analysis. The method
      enables characterization and quantification of feasible phenotypes in microbes.
      EFM analysis was employed to characterize the phenotype of Corynebacterium
      glutamicum to yield various amino acids. The metabolic network of C. glutamicum
      yielded 62 elementary modes by incorporating the accumulation of amino acids
      namely, lysine, alanine, valine, glutamine and glutamate. The analysis also
      allowed us to compute the maximum theoretical yield for the synthesis of various
      amino acids. These 62 elementary modes were further used to obtain optimal
      phenotypic space towards accumulation of biomass and lysine. The study indicated
      that the optimal solution space from 62 elementary modes forms a super space
      which incorporates various mutants including lysine producing strain of C.
      glutamicum. The analysis was also extended to obtain sensitivity of the network
      to variation in the stoichiometry of NADP in the definition of biomass.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11693-011-9073-8) contains supplementary material, which is
      available to authorized users.

PMID- 22132056
TI  - Structure prediction and validation of an affibody engineered for cell-specific
      nucleic acid targeting.
AB  - Cell-penetrating peptides comprising cloned epitopes that contribute to membrane
      transduction, DNA-binding and cell targeting functions are known to facilitate
      nucleic acid delivery. Using the ITASSER software, we predicted the 3-D structure
      of a well characterized and efficient transfecting cell-penetrating peptide,
      namely TAT-Mu and its derivative TAT-Mu-AF protein that harbors a targeting
      ligand, the HER2-binding affibody. Our model predicts TAT-Mu-AF fusion protein as
      primarily comprising alpha-helices. The affibody in TAT-Mu-AF is predicted as a 3
      helical domain that is distinct from the TAT-Mu domain. Its positioning in three
      dimensional structure is oriented in a manner that possibly favors interactions
      with receptor and facilitates transport to the target site. The linker region
      between TAT-Mu and the affibody is also predicted as a helix that is likely to
      stabilize the overall fold of the TAT-Mu-AF complex. Further, the evaluation of
      secondary structure of the designed TAT-Mu-AF fusion protein by circular
      dichroism is in support of our predictions.

PMID- 22132057
TI  - Modeling metabolic adjustment in Mycobacterium tuberculosis upon treatment with
      isoniazid.
AB  - Complex biological systems exhibit a property of robustness at all levels of
      organization. Through different mechanisms, the system tries to sustain stress
      such as due to starvation or drug exposure. To explore whether reconfiguration of
      the metabolic networks is used as a means to achieve robustness, we have studied
      possible metabolic adjustments in Mtb upon exposure to isoniazid (INH), a front
      line clinical drug. The redundancy in the genome of M. tuberculosis (Mtb) makes
      it an attractive system to explore if alternate routes of metabolism exist in the
      bacterium. While the mechanism of action of INH is well studied, its effect on
      the overall metabolism is not well characterized. Using flux balance analysis,
      inhibiting the fluxes flowing through the reactions catalyzed by Rv1484, the
      target of INH, significantly changes the overall flux profiles. At the pathway
      level, activation or inactivation of certain pathways distant from the target
      pathway, are seen. Metabolites such as NADPH are shown to reduce drastically,
      while fatty acids tend to accumulate. The overall biomass also decreases with
      increasing inhibition levels. Inhibition studies, pathway level clustering and
      comparison of the flux profiles with the gene expression data indicate the
      activation of folate metabolism, ubiquinone metabolism, and metabolism of certain
      amino acids. This analysis provides insights useful for target identification and
      designing strategies for combination therapy. Insights gained about the role of
      individual components of a system and their interactions will also provide a
      basis for reconstruction of whole systems through synthetic biology approaches.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11693-011-9075-6) contains supplementary material, which is
      available to authorized users.

PMID- 22132058
TI  - Protein-protein interaction networks suggest different targets have different
      propensities for triggering drug resistance.
AB  - Emergence of drug resistance is a major problem in the treatment of many diseases
      including tuberculosis. To tackle the problem from a wholistic perspective, it is
      essential to understand the molecular mechanisms by which bacteria acquire drug
      resistance using a systems approach. Availability of genome-scale data of
      expression profiles under different drug exposed conditions and protein-protein
      interactions, makes it feasible to reconstruct and analyze systems-level models.
      A number of proteins involved in different resistance mechanisms, referred to as
      the resistome are identified from literature. The interaction of the drug
      directly with the resistome is unable to explain most resistance processes
      adequately, including that of increased mutations in the target's binding site.
      We recently hypothesized that some communication might exist from the drug
      environment to the resistome to trigger emergence of drug resistance. We report
      here a network based approach to identify most plausible paths of such
      communication in Mycobacterium tuberculosis. Networks capturing both structural
      and functional linkages among various proteins were weighted based on gene
      expression profiles upon exposure to specific drugs and betweenness centrality of
      the interactions. Our analysis suggests that different drug targets and hence
      different drugs could trigger the resistome to different extents and through
      different routes. The identified paths correlate well with the mechanisms known
      through experiment. Some examples of the top ranked hubs in multiple drug
      specific networks are PolA, FadD1, CydA, a monoxygenase and GltS, which could
      serve as co-targets, that could be inhibited in order to retard resistance
      related communication in the cell.

PMID- 22132059
TI  - Re-programming DNA-binding specificity in zinc finger proteins for targeting
      unique address in a genome.
AB  - Recent studies provide a glimpse of future potential therapeutic applications of
      custom-designed zinc finger proteins in achieving highly specific genomic
      manipulation. Custom-design of zinc finger proteins with tailor-made specificity
      is currently limited by the availability of information on recognition helices
      for all possible DNA targets. However, recent advances suggest that a combination
      of design and selection method is best suited to identify custom zinc finger DNA
      binding proteins for known genome target sites. Design of functionally self
      contained zinc finger proteins can be achieved by (a) modular protein engineering
      and (b) computational prediction. Here, we explore the novel functionality
      obtained by engineered zinc finger proteins and the computational approaches for
      prediction of recognition helices of zinc finger proteins that can raise our
      ability to re-program zinc finger proteins with desired novel DNA-binding
      specificities.

PMID- 22132060
TI  - Synthesis of robust tunable oscillators using mitogen activated protein kinase
      cascades.
AB  - Mitogen activated protein kinase (MAPK) cascade is evolutionally preserved in all
      eukaryotic cells, and regulates various cellular activities such as gene
      expression, mitosis, differentiation, and apoptosis. Recently, Bashor et al. have
      shown that Ste5 scaffold protein can be used to reshape the MAPK cascade through
      engineered feedback loops, and have used heuristic tuning mechanisms to
      synthesize the feedback. A problem of interest is to determine whether
      information regarding the underlying biochemical reactions can be used to
      synthesize robust feedback that will ensure that the resultant circuit has the
      desired properties. In this paper, we consider the problem of engineering
      feedback in MAPK cascade to synthesize an oscillator of the desired frequency.
      Our approach builds on the MAPK cascade model derived by Chikarmane et al. who
      have exploited the existence of a Hopf bifurcation point in the Markevich model
      of the MAPK cascade to synthesize the exciting kinase as a function of the doubly
      phosphorylated protein. We show how the [Formula: see text]-control theory can be
      used for a robust synthesis of the oscillator and present the simulation results.

PMID- 22132061
TI  - Implications of copy number variation in people with chromosomal abnormalities:
      potential for greater variation in copy number state may contribute to
      variability of phenotype.
AB  - Copy number variation is common in the human genome with many regions,
      overlapping thousands of genes, now known to be deleted or amplified.
      Aneuploidies and other forms of chromosomal imbalance have a wide range of
      adverse phenotypes and are a common cause of birth defects resulting in
      significant morbidity and mortality. "Normal" copy number variants (CNVs)
      embedded within the regions of chromosome imbalance may affect the clinical
      outcomes by altering the local copy number of important genes or regulatory
      regions: this could alleviate or exacerbate certain phenotypes. In this way CNVs
      may contribute to the clinical variability seen in many disorders caused by
      chromosomal abnormalities, such as the congenital heart defects (CHD) seen in
      ~40% of Down's syndrome (DS) patients. Investigation of CNVs may therefore help
      to pinpoint critical genes or regulatory elements, elucidating the molecular
      mechanisms underlying these conditions, also shedding light on the aetiology of
      such phenotypes in people without major chromosome imbalances, and ultimately
      leading to their improved detection and treatment.

PMID- 22132063
TI  - Genome-wide identification and annotation of HIF-1alpha binding sites in two cell
      lines using massively parallel sequencing.
AB  - We identified 531 and 616 putative HIF-1alpha target sites by ChIP-Seq in the
      cancerous cell line DLD-1 and the non-cancerous cell line TIG-3, respectively. We
      also examined the positions and expression levels of transcriptional start sites
      (TSSs) in these cell lines using our TSS-Seq method. We observed that 121 and 48
      genes in DLD-1 and TIG-3 cells, respectively, had HIF-1alpha binding sites in
      proximal regions of the previously reported TSSs that were up-regulated at the
      transcriptional level. In addition, 193 and 123 of the HIF-1alpha target sites,
      respectively, were located in proximal regions of previously uncharacterized
      TSSs, namely, TSSs of putative alternative promoters of protein-coding genes or
      promoters of putative non-protein-coding transcripts. The hypoxic response of DLD
      1 cells was more significant than that of TIG-3 cells with respect to both the
      number of target sites and the degree of induced changes in transcript
      expression. The Nucleosome-Seq and ChIP-Seq analyses of histone modifications
      revealed that the chromatin formed an open structure in regions surrounding the
      HIF-1alpha binding sites, but this event occurred prior to the actual binding of
      HIF-1alpha. Different cellular histories may be encoded by chromatin structures
      and determine the activation of specific genes in response to hypoxic shock.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11568-011-9150-9) contains supplementary material, which is
      available to authorized users.

PMID- 22132064
TI  - The GAMY Project: young people's attitudes to genetics in the South Wales
      valleys.
AB  - This paper explores young people's attitudes to genetics. It describes a
      qualitative study involving a group of teenagers in a deprived South Wales valley
      town over a period of 18 months. The GAMY (Genetics and Merthyr Youth) Project
      involved a series of interactions with participants, including 2 interviews, 4
      group days and 4 genetics tasks through which these young people learned about,
      and then reflected upon, issues relating to genetics and health. We have gathered
      data about the informed attitudes of teenagers to genetics based on deliberative
      learning and reflection over a long period of time, and as such this paper
      provides useful insights into the underlying values that are guiding young
      people's views and the factors that are shaping their responses to new genetic
      technologies. Attitudes to genetics are complex and not easily generalisable.
      There were low levels of familiarity with, and knowledge of, genetics from the
      outset. Most young people did not have pre-existing attitudes towards genetics
      and had given little or no thought to the topic before the project began.
      However, levels of awareness and general genetic literacy increased as the
      project progressed. This study suggests that over time young people can develop
      an awareness of genetics that makes sense to them; they demonstrate that they can
      think creatively about genetics, and they are able to engage in considering
      genetic and other risk factors when thinking about health and disease.

PMID- 22132062
TI  - Current status and future potential of somatic mutation testing from circulating
      free DNA in patients with solid tumours.
AB  - Genetic alterations can determine the natural history of cancer and its treatment
      response. With further advances in DNA sequencing technology, multiple novel
      genetic alterations will be discovered which could be exploited as prognostic,
      predictive and pharmacodynamic biomarkers in the development and use of cancer
      therapeutics. As such, the importance in clinical practice of efficient and
      robust somatic mutation testing in solid tumours cannot be overemphasized in the
      current era of personalized medicine. However, significant challenges remain
      regarding the testing of genetic biomarkers in clinical practice. Reliance on
      archived formalin fixed, paraffin embedded tumour, obtained from diagnostic
      biopsies, for testing somatic genetic alterations could restrict the scientific
      community in asking relevant questions about a patient's cancer biology. Problems
      inherent with using formalin fixed, archival tissue are well recognized and
      difficult to resolve. It could be argued that to achieve rapid and efficient
      incorporation of genetic biomarkers into clinical practice, somatic mutation
      testing in cancer patients should be simpler, less invasive using a readily
      available clinical sample, whilst maintaining robustness and reproducibility. In
      this regard, use of circulating free DNA (cfDNA) from plasma or serum as an
      alternative and/or additional source of DNA to test cancer specific genetic
      alterations is an attractive proposition. In light of encouraging results from
      recent studies, this mini review will discuss the current role and future
      potential of somatic mutation testing from circulating or cell free DNA derived
      from the blood of patients with solid tumours.

PMID- 22132066
TI  - Designer lipid-like peptides: a class of detergents for studying functional
      olfactory receptors using commercial cell-free systems.
AB  - A crucial bottleneck in membrane protein studies, particularly G-protein coupled
      receptors, is the notorious difficulty of finding an optimal detergent that can
      solubilize them and maintain their stability and function. Here we report rapid
      production of 12 unique mammalian olfactory receptors using short designer lipid
      like peptides as detergents. The peptides were able to solubilize and stabilize
      each receptor. Circular dichroism showed that the purified olfactory receptors
      had alpha-helical secondary structures. Microscale thermophoresis suggested that
      the receptors were functional and bound their odorants. Blot intensity
      measurements indicated that milligram quantities of each olfactory receptor could
      be produced with at least one peptide detergent. The peptide detergents'
      capability was comparable to that of the detergent Brij-35. The ability of 10
      peptide detergents to functionally solubilize 12 olfactory receptors demonstrates
      their usefulness as a new class of detergents for olfactory receptors, and
      possibly other G-protein coupled receptors and membrane proteins.

PMID- 22132067
TI  - Additive functions in boolean models of gene regulatory network modules.
AB  - Gene-on-gene regulations are key components of every living organism. Dynamical
      abstract models of genetic regulatory networks help explain the genome's
      evolvability and robustness. These properties can be attributed to the structural
      topology of the graph formed by genes, as vertices, and regulatory interactions,
      as edges. Moreover, the actual gene interaction of each gene is believed to play
      a key role in the stability of the structure. With advances in biology, some
      effort was deployed to develop update functions in boolean models that include
      recent knowledge. We combine real-life gene interaction networks with novel
      update functions in a boolean model. We use two sub-networks of biological
      organisms, the yeast cell-cycle and the mouse embryonic stem cell, as topological
      support for our system. On these structures, we substitute the original random
      update functions by a novel threshold-based dynamic function in which the
      promoting and repressing effect of each interaction is considered. We use a third
      real-life regulatory network, along with its inferred boolean update functions to
      validate the proposed update function. Results of this validation hint to
      increased biological plausibility of the threshold-based function. To investigate
      the dynamical behavior of this new model, we visualized the phase transition
      between order and chaos into the critical regime using Derrida plots. We
      complement the qualitative nature of Derrida plots with an alternative measure,
      the criticality distance, that also allows to discriminate between regimes in a
      quantitative way. Simulation on both real-life genetic regulatory networks show
      that there exists a set of parameters that allows the systems to operate in the
      critical region. This new model includes experimentally derived biological
      information and recent discoveries, which makes it potentially useful to guide
      experimental research. The update function confers additional realism to the
      model, while reducing the complexity and solution space, thus making it easier to
      investigate.

PMID- 22132069
TI  - MetaBinG: using GPUs to accelerate metagenomic sequence classification.
AB  - Metagenomic sequence classification is a procedure to assign sequences to their
      source genomes. It is one of the important steps for metagenomic sequence data
      analysis. Although many methods exist, classification of high-throughput
      metagenomic sequence data in a limited time is still a challenge. We present here
      an ultra-fast metagenomic sequence classification system (MetaBinG) using graphic
      processing units (GPUs). The accuracy of MetaBinG is comparable to the best
      existing systems and it can classify a million of 454 reads within five minutes,
      which is more than 2 orders of magnitude faster than existing systems. MetaBinG
      is publicly available at
      http://cbb.sjtu.edu.cn/~ccwei/pub/software/MetaBinG/MetaBinG.php.

PMID- 22132068
TI  - Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis
      factor mice.
AB  - Of those individuals who are infected with M. tuberculosis, 90% do not develop
      active disease and represents a large reservoir of M. tuberculosis with the
      potential for reactivation of infection. Sustained TNF expression is required for
      containment of persistent infection and TNF neutralization leads to tuberculosis
      reactivation. In this study, we investigated the contribution of soluble TNF
      (solTNF) and transmembrane TNF (Tm-TNF) in immune responses generated against
      reactivating tuberculosis. In a chemotherapy induced tuberculosis reactivation
      model, mice were challenged by aerosol inhalation infection with low dose M.
      tuberculosis for three weeks to establish infection followed chemotherapeutic
      treatment for six weeks, after which therapy was terminated and tuberculosis
      reactivation investigated. We demonstrate that complete absence of TNF results in
      host susceptibility to M. tuberculosis reactivation in the presence of
      established mycobacteria-specific adaptive immunity with mice displaying
      unrestricted bacilli growth and diffused granuloma structures compared to WT
      control mice. Interestingly, bacterial re-emergence is contained in Tm-TNF mice
      during the initial phases of tuberculosis reactivation, indicating that Tm-TNF
      sustains immune pressure as in WT mice. However, Tm-TNF mice show susceptibility
      to long term M. tuberculosis reactivation associated with uncontrolled influx of
      leukocytes in the lungs and reduced IL-12p70, IFNgamma and IL-10, enlarged
      granuloma structures, and failure to contain mycobacterial replication relative
      to WT mice. In conclusion, we demonstrate that both solTNF and Tm-TNF are
      required for maintaining immune pressure to contain reactivating M. tuberculosis
      bacilli even after mycobacteria-specific immunity has been established.

PMID- 22132070
TI  - Cyclic AMP-dependent protein kinase A regulates the alternative splicing of
      CaMKIIdelta.
AB  - Ca(2+)/calmodulin-dependent protein kinase (CaMK) IIdelta is predominantly
      expressed in the heart. There are three isoforms of CaMKIIdelta resulting from
      the alternative splicing of exons 14, 15, and 16 of its pre-mRNA, which is
      regulated by the splicing factor SF2/ASF. Inclusion of exons 15 and 16 or of exon
      14 generates deltaA or deltaB isoform. The exclusion of all three exons gives
      rise to deltaC isoform, which is selectively increased in pressure-overload
      induced hypertrophy. Overexpression of either deltaB or deltaC induces
      hypertrophy and heart failure, suggesting their specific role in the pathogenesis
      of hypertrophy and heart failure. It is well known that the beta-adrenergic
      cyclic AMP-dependent protein kinase A (PKA) pathway is implicated in heart
      failure. To determine the role of PKA in the alternative splicing of CaMKIIdelta,
      we constructed mini-CaMKIIdelta genes and used these genes to investigate the
      regulation of the alternative splicing of CaMKIIdelta by PKA in cultured cells.
      We found that PKA promoted the exclusion of exons 14, 15, and 16 of CaMKIIdelta,
      resulting in an increase in deltaC isoform. PKA interacted with and
      phosphorylated SF2/ASF, and enhanced SF2/ASF's activity to promote the exclusion
      of exons 14, 15, and 16 of CaMKIIdelta, leading to a further increase in the
      expression of deltaC isoform. These findings suggest that abnormality in beta
      adrenergic-PKA signaling may contribute to cardiomyopathy and heart failure
      through dysregulation in the alternative splicing of CaMKIIdelta exons 14, 15,
      and 16 and up-regulation of CaMKIIdeltaC.

PMID- 22132071
TI  - Structural analysis of prolyl oligopeptidases using molecular docking and
      dynamics: insights into conformational changes and ligand binding.
AB  - Prolyl oligopeptidase (POP) is considered as an important pharmaceutical target
      for the treatment of numerous diseases. Despite enormous studies on various
      aspects of POPs structure and function still some of the questions are intriguing
      like conformational dynamics of the protein and interplay between ligand
      entry/egress. Here, we have used molecular modeling and docking based approaches
      to unravel questions like differences in ligand binding affinities in three POP
      species (porcine, human and A. thaliana). Despite high sequence and structural
      similarity, they possess different affinities for the ligands. Interestingly,
      human POP was found to be more specific, selective and incapable of binding to a
      few planar ligands which showed extrapolation of porcine POP in human context is
      more complicated. Possible routes for substrate entry and product egress were
      also investigated by detailed analyses of molecular dynamics (MD) simulations for
      the three proteins. Trajectory analysis of bound and unbound forms of three
      species showed differences in conformational dynamics, especially variations in
      beta-propeller pore size, which was found to be hidden by five lysine residues
      present on blades one and seven. During simulation, beta-propeller pore size was
      increased by ~2 A in porcine ligand-bound form which might act as a passage for
      smaller product movement as free energy barrier was reduced, while there were no
      significant changes in human and A. thaliana POPs. We also suggest that these
      differences in pore size could lead to fundamental differences in mode of product
      egress among three species. This analysis also showed some functionally important
      residues which can be used further for in vitro mutagenesis and inhibitor design.
      This study can help us in better understanding of the etiology of POPs in several
      neurodegenerative diseases.

PMID- 22132072
TI  - Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models
      neurodevelopmental psychopathology.
AB  - Psychiatric disorders such as schizophrenia and autism are characterised by
      cellular disorganisation and dysconnectivity across the brain and can be caused
      by mutations in genes that control neurodevelopmental processes. To examine how
      neurodevelopmental defects can affect brain function and behaviour, we have
      comprehensively investigated the consequences of mutation of one such gene,
      Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour
      and physiology in mice. These analyses reveal a spectrum of widespread but subtle
      anatomical defects in Sema6A mutants, notably in limbic and cortical cellular
      organisation, lamination and connectivity. These mutants display concomitant
      alterations in the electroencephalogram and hyper-exploratory behaviour, which
      are characteristic of models of psychosis and reversible by the antipsychotic
      clozapine. They also show altered social interaction and deficits in object
      recognition and working memory. Mice with mutations in Sema6A or the interacting
      genes may thus represent a highly informative model for how neurodevelopmental
      defects can lead to anatomical dysconnectivity, resulting, either directly or
      through reactive mechanisms, in dysfunction at the level of neuronal networks
      with associated behavioural phenotypes of relevance to psychiatric disorders. The
      biological data presented here also make these genes plausible candidates to
      explain human linkage findings for schizophrenia and autism.

PMID- 22132073
TI  - Association between Prostinogen (KLK15) genetic variants and prostate cancer risk
      and aggressiveness in Australia and a meta-analysis of GWAS data.
AB  - BACKGROUND: Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for
      prostate cancer susceptibility. Elevated KLK15 expression has been reported in
      prostate cancer and it has been described as an unfavorable prognostic marker for
      the disease. OBJECTIVES: We performed a comprehensive analysis of association of
      variants in the KLK15 gene with prostate cancer risk and aggressiveness by
      genotyping tagSNPs, as well as putative functional SNPs identified by extensive
      bioinformatics analysis.  METHODS AND DATA SOURCES: Twelve out of 22 SNPs,
      selected on the basis of linkage disequilibrium pattern, were analyzed in an
      Australian sample of 1,011 histologically verified prostate cancer cases and
      1,405 ethnically matched controls. Replication was sought from two existing
      genome wide association studies (GWAS): the Cancer Genetic Markers of
      Susceptibility (CGEMS) project and a UK GWAS study. RESULTS: Two KLK15 SNPs,
      rs2659053 and rs3745522, showed evidence of association (p<0.05) but were not
      present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated
      with prostate cancer aggressiveness and showed evidence of association in a
      replication cohort of 5,051 patients from the UK, Australia, and the CGEMS
      dataset of US samples. A highly significant association with Gleason score was
      observed when the data was combined from these three studies with an Odds Ratio
      (OR) of 0.85 (95% CI = 0.77-0.93; p = 2.7*10(-4)). The rs2659056 SNP is predicted
      to alter binding of the RORalpha transcription factor, which has a role in the
      control of cell growth and differentiation and has been suggested to control the
      metastatic behavior of prostate cancer cells. CONCLUSIONS: Our findings suggest a
      role for KLK15 genetic variation in the etiology of prostate cancer among men of
      European ancestry, although further studies in very large sample sets are
      necessary to confirm effect sizes.

PMID- 22132074
TI  - A metaproteomic approach to study human-microbial ecosystems at the mucosal
      luminal interface.
AB  - Aberrant interactions between the host and the intestinal bacteria are thought to
      contribute to the pathogenesis of many digestive diseases. However, studying the
      complex ecosystem at the human mucosal-luminal interface (MLI) is challenging and
      requires an integrative systems biology approach. Therefore, we developed a novel
      method integrating lavage sampling of the human mucosal surface, high-throughput
      proteomics, and a unique suite of bioinformatic and statistical analyses. Shotgun
      proteomic analysis of secreted proteins recovered from the MLI confirmed the
      presence of both human and bacterial components. To profile the MLI metaproteome,
      we collected 205 mucosal lavage samples from 38 healthy subjects, and subjected
      them to high-throughput proteomics. The spectral data were subjected to a
      rigorous data processing pipeline to optimize suitability for quantitation and
      analysis, and then were evaluated using a set of biostatistical tools. Compared
      to the mucosal transcriptome, the MLI metaproteome was enriched for extracellular
      proteins involved in response to stimulus and immune system processes. Analysis
      of the metaproteome revealed significant individual-related as well as anatomic
      region-related (biogeographic) features. Quantitative shotgun proteomics
      established the identity and confirmed the biogeographic association of 49
      proteins (including 3 functional protein networks) demarcating the proximal and
      distal colon. This robust and integrated proteomic approach is thus effective for
      identifying functional features of the human mucosal ecosystem, and a fresh
      understanding of the basic biology and disease processes at the MLI.

PMID- 22132075
TI  - Multiple cytokines are released when blood from patients with tuberculosis is
      stimulated with Mycobacterium tuberculosis antigens.
AB  - BACKGROUND: Mycobacterium tuberculosis (Mtb) infection may cause overt disease or
      remain latent. Interferon gamma release assays (IGRAs) detect Mtb infection, both
      latent infection and infection manifesting as overt disease, by measuring whole
      blood interferon gamma (IFN-gamma) responses to Mtb antigens such as early
      secreted antigenic target-6 (ESAT-6), culture filtrate protein 10 (CFP-10), and
      TB7.7. Due to a lack of adequate diagnostic standards for confirming latent Mtb
      infection, IGRA sensitivity for detecting Mtb infection has been estimated using
      patients with culture-confirmed tuberculosis (CCTB) for whom recovery of Mtb
      confirms the infection. In this study, cytokines in addition to IFN-gamma were
      assessed for potential to provide robust measures of Mtb infection. METHODS:
      Cytokine responses to ESAT-6, CFP-10, TB7.7, or combinations of these Mtb
      antigens, for patients with CCTB were compared with responses for subjects at low
      risk for Mtb infection (controls). Three different multiplexed immunoassays were
      used to measure concentrations of 9 to 20 different cytokines. Responses were
      calculated by subtracting background cytokine concentrations from cytokine
      concentrations in plasma from blood stimulated with Mtb antigens. RESULTS: Two
      assays demonstrated that ESAT-6, CFP-10, ESAT-6+CFP-10, and ESAT-6+CFP-10+TB7.7
      stimulated the release of significantly greater amounts of IFN-gamma, IL-2, IL-8,
      MCP-1 and MIP-1beta for CCTB patients than for controls. Responses to combination
      antigens were, or tended to be, greater than responses to individual antigens. A
      third assay, using whole blood stimulation with ESAT-6+CFP-10+TB7.7, revealed
      significantly greater IFN-gamma, IL-2, IL-6, IL-8, IP-10, MCP-1, MIP-1beta, and
      TNF-alpha responses among patients compared with controls. One CCTB patient with
      a falsely negative IFN-gamma response had elevated responses with other
      cytokines. CONCLUSIONS: Multiple cytokines are released when whole blood from
      patients with CCTB is stimulated with Mtb antigens. Measurement of multiple
      cytokine responses may improve diagnostic sensitivity for Mtb infection compared
      with assessment of IFN-gamma alone.

PMID- 22132076
TI  - Evaluation of high-throughput PCR and microarray-based assay in conjunction with
      automated DNA extraction instruments for diagnosis of sepsis.
AB  - BACKGROUND: High incidence of septic patients increases the pressure of faster
      and more reliable bacterial identification methods to adapt patient management
      towards focused and effective treatment options. The aim of this study was to
      assess two automated DNA extraction solutions with the PCR and microarray-based
      assay to enable rapid and reliable detection and speciation of causative agents
      in the diagnosis of sepsis. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated two
      automated DNA instruments NucliSENS(r) easyMAG(r) and NorDiag Arrow for the
      preparation of blood culture samples. A set of 91 samples flagged as positive
      during incubation was analyzed prospectively with the high-throughput generation
      of Prove-itTM Sepsis assay designed to identify over 60 gram-negative and gram
      positive bacterial species as well as methicillin resistance marker from a blood
      culture. Bacterial findings were accurately reported from 77 blood culture
      samples, whereas 14 samples were reported as negative, containing bacteria not
      belonging to the pathogen panel of the assay. No difference was observed between
      the performance of NorDiag Arrow or NucliSENS(r) easyMAG(r) with regard to the
      result reporting of Prove-itTM Sepsis. In addition, we also assessed the quality
      and quantity of DNA extracted from the clinical Escherichia coli isolate with DNA
      extraction instruments. We observed only minor differences between the two
      instruments. CONCLUSIONS: Use of automated and standardized sample preparation
      methods together with rapid, multiplex pathogen detection offers a strategy to
      speed up reliably the diagnostics of septic patients. Both tested DNA extraction
      devices were shown to be feasible for blood culture samples and the Prove-itTM
      Sepsis assay, providing an accurate identification of pathogen within 4.5 hours
      when the detected pathogen was in the repertoire of the test.

PMID- 22132077
TI  - A hierarchical bayesian approach to ecological count data: a flexible tool for
      ecologists.
AB  - Many ecological studies use the analysis of count data to arrive at biologically
      meaningful inferences. Here, we introduce a hierarchical bayesian approach to
      count data. This approach has the advantage over traditional approaches in that
      it directly estimates the parameters of interest at both the individual-level and
      population-level, appropriately models uncertainty, and allows for comparisons
      among models, including those that exceed the complexity of many traditional
      approaches, such as ANOVA or non-parametric analogs. As an example, we apply this
      method to oviposition preference data for butterflies in the genus Lycaeides.
      Using this method, we estimate the parameters that describe preference for each
      population, compare the preference hierarchies among populations, and explore
      various models that group populations that share the same preference hierarchy.

PMID- 22132078
TI  - Bird diversity, birdwatching tourism and conservation in Peru: a geographic
      analysis.
AB  - In the face of the continuing global biodiversity loss, it is important not only
      to assess the need for conservation, through e.g. gap analyses, but also to seek
      practical solutions for protecting biodiversity. Environmentally and socially
      sustainable tourism can be one such solution. We present a method to spatially
      link data on conservation needs and tourism-based economic opportunities, using
      bird-related tourism in Peru as an example. Our analysis highlighted areas in
      Peru where potential for such projects could be particularly high. Several areas
      within the central and northern Andean regions, as well as within the lowland
      Amazonian regions of Madre de Dios and Loreto emerge as promising for this type
      of activity. Mechanisms to implement conservation in these areas include e.g.
      conservation and ecotourism concessions, private conservation areas, and
      conservation easements. Some of these mechanisms also offer opportunities for
      local communities seeking to secure their traditional land ownership and use
      rights. (Spanish language abstract, Abstract S1).

PMID- 22132079
TI  - Shapes of discoid intracellular compartments with small relative volumes.
AB  - A prominent feature of many intracellular compartments is a large membrane
      surface area relative to their luminal volume, i.e., the small relative volume.
      In this study we present a theoretical analysis of discoid membrane compartments
      with a small relative volume and then compare the theoretical results to
      quantitative morphological assessment of fusiform vesicles in urinary bladder
      umbrella cells. Specifically, we employ three established extensions of the
      standard approach to lipid membrane shape calculation and determine the shapes
      that could be expected according to three scenarios of membrane shaping: membrane
      adhesion in the central discoid part, curvature driven lateral segregation of
      membrane constituents, and existence of stiffer membrane regions, e.g., support
      by protein scaffolds. The main characteristics of each scenario are analyzed. The
      results indicate that even though all three scenarios can lead to similar shapes,
      there are values of model parameters that yield qualitatively distinctive shapes.
      Consequently, a distinctive shape of an intracellular compartment may reveal its
      membrane shaping mechanism and the membrane structure. The observed shapes of
      fusiform vesicles fall into two qualitatively different classes, yet they are all
      consistent with the theoretical results and the current understanding of their
      structure and function.

PMID- 22132080
TI  - Ring-like distribution of constitutive heterochromatin in bovine senescent cells.
AB  - BACKGROUND: Cells that reach "Hayflick limit" of proliferation, known as
      senescent cells, possess a particular type of nuclear architecture. Human
      senescent cells are characterized by the presence of highly condensed senescent
      associated heterochromatin foci (SAHF) that can be detected both by
      immunostaining for histone H3 three-methylated at lysine 9 (H3K9me3) and by DAPI
      counterstaining. METHODS: We have studied nuclear architecture in bovine
      senescent cells using a combination of immunofluorescence and 3D fluorescent in
      situ hybridization (FISH). RESULTS: Analysis of heterochromatin distribution in
      bovine senescent cells using fluorescent in situ hybridization for pericentric
      chromosomal regions, immunostaining of H3K9me3, centromeric proteins CENP A/B and
      DNA methylation showed a lower level of heterochromatin condensation as compared
      to young cells. No SAHF foci were observed. Instead, we observed fibrous ring
      like or ribbon-like heterochromatin patterns that were undetectable with DAPI
      counterstaining. These heterochromatin fibers were associated with nucleoli.
      CONCLUSIONS: Constitutive heterochromatin in bovine senescent cells is organized
      in ring-like structures.

PMID- 22132081
TI  - Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?
AB  - Mutations in insulin/IGF-1 signaling pathway have been shown to lead to increased
      longevity in various invertebrate models. Therefore, the effect of the haplo
      insufficiency of the IGF-1 receptor (Igf1r(+/-)) on longevity/aging was evaluated
      in C57Bl/6 mice using rigorous criteria where lifespan and end-of-life pathology
      were measured under optimal husbandry conditions using large sample sizes.
      Igf1r(+/-) mice exhibited reductions in IGF-1 receptor levels and the activation
      of Akt by IGF-1, with no compensatory increases in serum IGF-1 or tissue IGF-1
      mRNA levels, indicating that the Igf1r(+/-) mice show reduced IGF-1 signaling.
      Aged male, but not female Igf1r(+/-) mice were glucose intolerant, and both
      genders developed insulin resistance as they aged. Female, but not male Igf1r(+/
      ) mice survived longer than wild type mice after lethal paraquat and diquat
      exposure, and female Igf1r(+/-) mice also exhibited less diquat-induced liver
      damage. However, no significant difference between the lifespans of the male
      Igf1r(+/-) and wild type mice was observed; and the mean lifespan of the Igf1r(+/
      ) females was increased only slightly (less than 5%) compared to wild type mice.
      A comprehensive pathological analysis showed no significant difference in end-of
      life pathological lesions between the Igf1r(+/-) and wild type mice. These data
      show that the Igf1r(+/-) mouse is not a model of increased longevity and delayed
      aging as predicted by invertebrate models with mutations in the insulin/IGF-1
      signaling pathway.

PMID- 22132082
TI  - Structure analysis of a new psychrophilic marine protease.
AB  - A new psychrophilic marine protease was found from a marine bacterium
      Flavobacterium YS-80 in the Chinese Yellow Sea. The protease is about 49 kD with
      an isoelectric point about 4.5. It consists of 480 amino acids and is homologous
      to a psychrophilic alkaline protease (PAP) from an Antarctic Pseudomonas species.
      The protein was purified from the natural bacterium fermented and crystallized.
      Its crystal structure (PDB ID 3U1R) was solved at 2.0 A by Molecular Replacement
      using a model based on PAP, and was refined to a crystallographic R(work) of 0.16
      and an R(free) of 0.21. The marine protease consists of a two domain structure
      with an N-terminal domain including residues 37-264 and a C-terminal domain
      including residues 265-480. Similar to PAP, the N-terminal domain is responsible
      for proteolysis and the C-terminal is for stability. His186, His190, His196 and
      Tyr226 are ligands for the Zn(2+) ion in the catalytic center. The enzyme's
      Tyr226 is closer to the Zn(2+) ion than in PAP and it shows a stronger Zn(2+)-Tyr
      OH bond. There are eight calcium ions in the marine protease molecule and they
      have significantly shorter bond distances to their ligands compared to their
      counterparts in all three crystal forms of PAP. On the other hand, the loops in
      the marine protease are more compact than in PAP. This makes the total structure
      stable and less flexible, resulting in higher thermo stability. These properties
      are consistent with the respective environments of the proteases. The structural
      analysis of this new marine protease provides new information for the study of
      psychrophilic proteases and is helpful for elucidating the structure-environment
      adaptation of these enzymes.

PMID- 22132083
TI  - Enhanced Hsp70 expression protects against acute lung injury by modulating
      apoptotic pathways.
AB  - The Acute respiratory distress syndrome (ARDS) is a highly lethal inflammatory
      lung disorder. Apoptosis plays a key role in its pathogenesis. We showed that an
      adenovirus expressing the 70 kDa heat shock protein Hsp70 (AdHSP) protected
      against sepsis-induced lung injury. In this study we tested the hypothesis that
      AdHSP attenuates apoptosis in sepsis-induced lung injury. Sepsis was induced in
      rats via cecal ligation and double puncture (2CLP). At the time of 2CLP PBS,
      AdHSP or AdGFP (an adenoviral vector expressing green fluorescent protein) were
      injected into the tracheas of septic rats. 48 hours later, lungs were isolated.
      One lung was fixed for TUNEL staining and immunohistochemistry. The other was
      homogenized to isolate cytosolic and nuclear protein. Immunoblotting, gel
      filtration and co-immunoprecipitation were performed in these extracts. In
      separate experiments MLE-12 cells were incubated with medium, AdHSP or AdGFP.
      Cells were stimulated with TNFalpha. Cytosolic and nuclear proteins were
      isolated. These were subjected to immunoblotting, co-immunoprecipitation and a
      caspase-3 activity assay. TUNEL assay demonstrated that AdHSP reduced alveolar
      cell apoptosis. This was confirmed by immunohistochemical detection of caspase 3
      abundance. In lung isolated from septic animals, immunoblotting, co
      immunoprecipitation and gel filtration studies revealed an increase in
      cytoplasmic complexes containing caspases 3, 8 and 9. AdHSP disrupted these
      complexes. We propose that Hsp70 impairs apoptotic cellular pathways via
      interactions with caspases. Disruption of large complexes resulted in
      stabilization of lower molecular weight complexes, thereby, reducing nuclear
      caspase-3. Prevention of apoptosis in lung injury may preserve alveolar cells and
      aid in recovery.

PMID- 22132084
TI  - Patchiness and co-existence of indigenous and invasive mussels at small spatial
      scales: the interaction of facilitation and competition.
AB  - Ecological theory predicts that two species with similar requirements will fail
      to show long-term co-existence in situations where shared resources are limiting,
      especially at spatial scales that are small relative to the size of the
      organisms. Two species of intertidal mussels, the indigenous Perna perna and the
      invasive Mytilus galloprovincialis, form mixed beds on the south coast of South
      Africa in a situation that has been stable for several generations of these
      species, even though these populations are often limited by the availability of
      space. We examined the spatial structure of these species where they co-exist at
      small spatial scales in the absence of apparent environmental heterogeneity at
      two sites, testing: whether conspecific aggregation of mussels can occur (using
      spatial Monte-Carlo tests); the degree of patchiness (using Korcak B patchiness
      exponent), and whether there was a relationship between percent cover and
      patchiness. We found that under certain circumstances there is non-random
      conspecific aggregation, but that in other circumstances there may be random
      distribution (i.e. the two species are mixed), so that spatial patterns are
      context-dependent. The relative cover of the species differed between sites, and
      within each site, the species with higher cover showed low Korcak B values
      (indicating low patchiness, i.e. the existence of fewer, larger patches), while
      the less abundant species showed the reverse, i.e. high patchiness. This
      relationship did not hold for either species within sites. We conclude that co
      existence between these mussels is possible, even at small spatial scales because
      each species is an ecological engineer and, while they have been shown to compete
      for space, this is preceded by initial facilitation. We suggest that a patchy
      pattern of co-existence is possible because of a balance between direct
      (competitive) and indirect (facilitative) interactions.

PMID- 22132085
TI  - Reduced coupling of oxidative phosphorylation in vivo precedes electron transport
      chain defects due to mild oxidative stress in mice.
AB  - Oxidative stress and mitochondrial function are at the core of many degenerative
      conditions. However, the interaction between oxidative stress and in vivo
      mitochondrial function is unclear. We used both pharmacological (2 week paraquat
      (PQ) treatment of wild type mice) and transgenic (mice lacking Cu, Zn-superoxide
      dismutase (SOD1(-/-))) models to test the effect of oxidative stress on in vivo
      mitochondrial function in skeletal muscle. Magnetic resonance and optical
      spectroscopy were used to measure mitochondrial ATP and oxygen fluxes and cell
      energetic state. In both models of oxidative stress, coupling of oxidative
      phosphorylation was significantly lower (lower P/O) at rest in vivo in skeletal
      muscle and was dose-dependent in the PQ model. Despite this reduction in
      efficiency, in vivo mitochondrial phosphorylation capacity (ATPmax) was
      maintained in both models, and ex vivo mitochondrial respiration in permeabilized
      muscle fibers was unchanged following PQ treatment. In association with the
      reduced P/O, PQ treatment led to a dose-dependent reduction in PCr/ATP ratio and
      increased phosphorylation of AMPK. These results indicate that oxidative stress
      uncouples oxidative phosphorylation in vivo and results in energetic stress in
      the absence of defects in the mitochondrial electron transport chain.

PMID- 22132086
TI  - Targeting of mitochondria-endoplasmic reticulum by fluorescent macrocyclic
      compounds.
AB  - BACKGROUND: Useful probes of the intracellular environment that target a specific
      organelle in order to allow direct observation of the changes in these regions is
      of high current interest. Macrocyclic ligands have already revealed themselves as
      important selective hosts in some biological applications, forming stable and
      specific complexes. Therefore, in this paper, several macrocyclic ligands are
      evaluated as potential molecular probes. METHODOLOGY: Four polyammonium
      macrocycles and one macrotricyclic bearing pyridine and phenanthroline
      chromophores have been synthesised and evaluated as molecular probes. The
      cytotoxicity of the compounds has been analyzed using human breast cancer cells
      (MCF-7), non-cancerous human dermal fibroblasts (NHDF) and human adult dermal
      skin fibroblasts from a breast cancer patient (P14). All the compounds showed low
      toxicity at concentrations ranging from 10 nM to 10 uM, except for
      [32]phen(2)N(4) which proved to be highly cytotoxic for MCF-7 cells. Flow
      cytometry studies evidenced that the percentage of apoptotic and necrotic MCF-7
      and NHDF cells induced by the compounds is considerably low. Also, flow cytometry
      analysis showed that some compounds seem to modify the mitochondrial membrane
      potential (MMP) of the cells. Fluorescence microscopy evidenced that compounds
      easily cross the plasma membrane (5 min) and accumulated into the mitochondria,
      as confirmed by co-localization with MitoTracker GreenTM. The fluorescence images
      also evidenced an intact mitochondria structure after 48 h. Moreover, reticular
      staining suggestive of endoplasmic reticulum (ER) localization, in addition to
      the mitochondrial one, has been found by confocal microscopy. CONCLUSION: Our
      study reveals that compounds Me(2)[28]py(2)N(6), cryptphen, [16]phenN(2),
      [30]phen(2)N(6), have low toxicity and localize in mitochondria and ER. The
      ability of these compounds for translocating the cellular membrane (5 min)
      without special conditioning of the cells or derivatization of the probe, the
      time-dependent localization (48 h) and the cellular viability provide a proof-of
      concept towards their use as promising probes towards biomedical studies.

PMID- 22132087
TI  - Optically mapping multiple bacterial genomes simultaneously in a single run.
AB  - Optical mapping of bacterial chromosomes provides an unambiguous low-resolution
      sequence scaffold of the entire chromosome. In comparison to some techniques,
      such as pulse field gel electrophoresis, cost and throughput limit the
      application of this technique outside of genome finishing. We have demonstrated
      the production of multiple bacterial maps using a single set of consumables; this
      significantly reduces the time and expense of map production.

PMID- 22132088
TI  - Microanatomy of adult zebrafish extraocular muscles.
AB  - Binocular vision requires intricate control of eye movement to align overlapping
      visual fields for fusion in the visual cortex, and each eye is controlled by 6
      extraocular muscles (EOMs). Disorders of EOMs are an important cause of
      symptomatic vision loss. Importantly, EOMs represent specialized skeletal muscles
      with distinct gene expression profile and susceptibility to neuromuscular
      disorders. We aim to investigate and describe the anatomy of adult zebrafish
      extraocular muscles (EOMs) to enable comparison with human EOM anatomy and
      facilitate the use of zebrafish as a model for EOM research. Using differential
      interference contrast (DIC), epifluorescence microscopy, and precise sectioning
      techniques, we evaluate the anatomy of zebrafish EOM origin, muscle course, and
      insertion on the eye. Immunofluorescence is used to identify components of
      tendons, basement membrane and neuromuscular junctions (NMJs), and to analyze
      myofiber characteristics. We find that adult zebrafish EOM insertions on the
      globe parallel the organization of human EOMs, including the close proximity of
      specific EOM insertions to one another. However, analysis of EOM origins reveals
      important differences between human and zebrafish, such as the common rostral
      origin of both oblique muscles and the caudal origin of the lateral rectus
      muscles. Thrombospondin 4 marks the EOM tendons in regions that are highly
      innervated, and laminin marks the basement membrane, enabling evaluation of
      myofiber size and distribution. The NMJs appear to include both en plaque and en
      grappe synapses, while NMJ density is much higher in EOMs than in somatic
      muscles. In conclusion, zebrafish and human EOM anatomy are generally homologous,
      supporting the use of zebrafish for studying EOM biology. However, anatomic
      differences exist, revealing divergent evolutionary pressures.

PMID- 22132089
TI  - Graduate entry medicine: selection criteria and student performance.
AB  - BACKGROUND: Graduate entry medicine raises new questions about the suitability of
      students with different backgrounds. We examine this, and the broader issue of
      effectiveness of selection and assessment procedures. METHODS: The data included
      background characteristics, academic record, interview score and performance in
      pre-clinical modular assessment for two years intake of graduate entry medical
      students. Exploratory factor analysis is a powerful method for reducing a large
      number of measures to a smaller group of underlying factors. It was used here to
      identify patterns within and between the selection and performance data.
      PRINCIPAL FINDINGS: Basic background characteristics were of little importance in
      predicting exam success. However, easily interpreted components were detected
      within variables comprising the 'selection' and 'assessment' criteria. Three
      selection components were identified ('Academic', 'GAMSAT', 'Interview') and four
      assessment components ('General Exam', 'Oncology', 'OSCE', 'Family Case Study').
      There was a striking lack of relationships between most selection and performance
      factors. Only 'General Exam' and 'Academic' showed a correlation (Pearson's r =
      0.55, p<0.001). CONCLUSIONS: This study raises questions about methods of student
      selection and their effectiveness in predicting performance and assessing
      suitability for a medical career. Admissions tests and most exams only confirmed
      previous academic achievement, while interview scores were not correlated with
      any consequent assessment.

PMID- 22132090
TI  - Strategies for metagenomic-guided whole-community proteomics of complex microbial
      environments.
AB  - Accurate protein identification in large-scale proteomics experiments relies upon
      a detailed, accurate protein catalogue, which is derived from predictions of open
      reading frames based on genome sequence data. Integration of mass spectrometry
      based proteomics data with computational proteome predictions from environmental
      metagenomic sequences has been challenging because of the variable overlap
      between proteomic datasets and corresponding short-read nucleotide sequence data.
      In this study, we have benchmarked several strategies for increasing microbial
      peptide spectral matching in metaproteomic datasets using protein predictions
      generated from matched metagenomic sequences from the same human fecal samples.
      Additionally, we investigated the impact of mass spectrometry-based filters (high
      mass accuracy, delta correlation), and de novo peptide sequencing on the number
      and robustness of peptide-spectrum assignments in these complex datasets. In
      summary, we find that high mass accuracy peptide measurements searched against
      non-assembled reads from DNA sequencing of the same samples significantly
      increased identifiable proteins without sacrificing accuracy.

PMID- 22132091
TI  - Fate of transgenic DNA from orally administered Bt MON810 maize and effects on
      immune response and growth in pigs.
AB  - We assessed the effect of short-term feeding of genetically modified (GM: Bt
      MON810) maize on immune responses and growth in weanling pigs and determined the
      fate of the transgenic DNA and protein in-vivo. Pigs were fed a diet containing
      38.9% GM or non-GM isogenic parent line maize for 31 days. We observed that IL-12
      and IFNgamma production from mitogenic stimulated peripheral blood mononuclear
      cells decreased (P<0.10) following 31 days of GM maize exposure. While Cry1Ab
      specific IgG and IgA were not detected in the plasma of GM maize-fed pigs, the
      detection of the cry1Ab gene and protein was limited to the gastrointestinal
      digesta and was not found in the kidneys, liver, spleen, muscle, heart or blood.
      Feeding GM maize to weanling pigs had no effect on growth performance or body
      weight. IL-6 and IL-4 production from isolated splenocytes were increased
      (P<0.05) in response to feeding GM maize while the proportion of CD4(+) T cells
      in the spleen decreased. In the ileum, the proportion of B cells and macrophages
      decreased while the proportion of CD4(+) T cells increased in GM maize-fed pigs.
      IL-8 and IL-4 production from isolated intraepithelial and lamina propria
      lymphocytes were also increased (P<0.05) in response to feeding GM maize. In
      conclusion, there was no evidence of cry1Ab gene or protein translocation to the
      organs and blood of weaning pigs. The growth of pigs was not affected by feeding
      GM maize. Alterations in immune responses were detected; however, their biologic
      relevance is questionable.

PMID- 22132092
TI  - Firm-level perspectives on public sector engagement with private healthcare
      providers: survey evidence from Ghana and Kenya.
AB  - BACKGROUND: Health systems in Sub-Saharan Africa (SSA) are in urgent need of
      improvement. The private health sector is a major provider of care in the region
      and it will remain a significant actor in the future. Any efforts by SSA
      governments to improve health systems performance therefore has to account for
      the private health sector. Regional and international actors increasingly
      recognize importance of effectively engaging with the private health sector, and
      initiatives to improve engagement are underway in several countries. However,
      there is little systematic analysis of private health providers' view and
      experience with engagement. METHODOLOGY/PRINCIPAL FINDINGS: In this study we
      surveyed private health facilities in Kenya and Ghana to understand the extent to
      which and how governments interact and engage with these facilities. The results
      suggest that government engagement with private health facilities is quite
      limited. The primary focus of this engagement is "command-and-control" type
      regulations to improve the quality of care. There is little attention paid to
      building the capacity of health care businesses through either technical or
      financial assistance. The vast majority of these facilities also receive no
      government assistance in meeting public health and social goals. Finally,
      government engagement with private pharmacies is often neglected and clinics
      receive a disproportionate share of government assistance.
      CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that there may be
      considerable untapped potential for greater engagement with private health
      facilities--particularly pharmacies. Improving engagement will likely help
      governments with limited resources to better take advantage of the private sector
      capacity to meet access and equity objectives and to accelerate the achievement
      of the Millennium Development Goals.

PMID- 22132093
TI  - Protein amino acid composition: a genomic signature of encephalization in
      mammals.
AB  - Large brains relative to body size represent an evolutionarily costly adaptation
      as they are metabolically expensive and demand substantial amounts of time to
      reach structural and functional maturity thereby exacerbating offspring mortality
      while delaying reproductive age. In spite of its cost and adaptive impact, no
      genomic features linked to brain evolution have been found. By conducting a
      genome-wide analysis in all 37 fully sequenced mammalian genomes, we show that
      encephalization is significantly correlated with overall protein amino acid
      composition. This correlation is not a by-product of changes in nucleotide
      content, lifespan, body size, absolute brain size or genome size; is independent
      of phylogenetic effects; and is not restricted to brain expressed genes. This is
      the first report of a relationship between this fundamental and complex trait and
      changes in protein AA usage, possibly reflecting the high selective demands
      imposed by the process of encephalization across mammalian lineages.

PMID- 22132094
TI  - Trends in health policy and systems research over the past decade: still too
      little capacity in low-income countries.
AB  - BACKGROUND: The past decade has seen several high-level events and documents
      committing to strengthening the field of health policy and systems research
      (HPSR) as a critical input to strengthening health systems. Specifically, they
      called for increased production, capacity to undertake and funding for HPSR. The
      objective of this paper is to assess the extent to which progress has been
      achieved, an important feedback for stakeholders in this field. METHODS AND
      FINDING: Two sources of data have been used. The first is a bibliometric analysis
      to assess growth in production of HPSR between 2003 and 2009. The six building
      blocks of the health system were used to define the scope of this search. The
      second is a survey of 96 research institutions undertaken in 2010 to assess the
      capacity and funding availability to undertake HPSR, compared with findings from
      the same survey undertaken in 2000 and 2008. Both analyses focus on HPSR relevant
      to low-income and middle-income countries (LMICs). Overall, we found an
      increasing trend of publications on HPSR in LMICs, although only 4% were led by
      authors from low-income countries (LICs). This is consistent with findings from
      the institutional survey, where despite improvements in infrastructure of
      research institutions, a minimal change has been seen in the level of experience
      of researchers within LIC institutions. Funding availability in LICs has
      increased notably to institutions in Sub-Saharan Africa; nonetheless, the overall
      increase has been modest in all regions. CONCLUSION: Although progress has been
      made in both the production and funding availability for HPSR, capacity to
      undertake the research locally has grown at a much slower pace, particularly in
      LICs where there is most need for this research. A firm commitment to dedicate a
      proportion of all future funding for research to building capacity may be the
      only solution to turn the tide.

PMID- 22132095
TI  - Pseudomonas syringae pv. actinidiae draft genomes comparison reveal strain
      specific features involved in adaptation and virulence to Actinidia species.
AB  - A recent re-emerging bacterial canker disease incited by Pseudomonas syringae pv.
      actinidiae (Psa) is causing severe economic losses to Actinidia chinensis and A.
      deliciosa cultivations in southern Europe, New Zealand, Chile and South Korea.
      Little is known about the genetic features of this pathovar. We generated genome
      wide Illumina sequence data from two Psa strains causing outbreaks of bacterial
      canker on the A. deliciosa cv. Hayward in Japan (J-Psa, type-strain of the
      pathovar) and in Italy (I-Psa) in 1984 and 1992, respectively as well as from a
      Psa strain (I2-Psa) isolated at the beginning of the recent epidemic on A.
      chinensis cv. Hort16A in Italy. All strains were isolated from typical leaf spot
      symptoms. The phylogenetic relationships revealed that Psa is more closely
      related to P. s. pv. theae than to P. avellanae within genomospecies 8.
      Comparative genomic analyses revealed both relevant intrapathovar variations and
      putative pathovar-specific genomic regions in Psa. The genomic sequences of J-Psa
      and I-Psa were very similar. Conversely, the I2-Psa genome encodes four
      additional effector protein genes, lacks a 50 kb plasmid and the phaseolotoxin
      gene cluster, argK-tox but has acquired a 160 kb plasmid and putative prophage
      sequences. Several lines of evidence from the analysis of the genome sequences
      support the hypothesis that this strain did not evolve from the Psa population
      that caused the epidemics in 1984-1992 in Japan and Italy but rather is the
      product of a recent independent evolution of the pathovar actinidiae for
      infecting Actinidia spp. All Psa strains share the genetic potential for copper
      resistance, antibiotic detoxification, high affinity iron acquisition and
      detoxification of nitric oxide of plant origin. Similar to other sequenced
      phytopathogenic pseudomonads associated with woody plant species, the Psa strains
      isolated from leaves also display a set of genes involved in the catabolism of
      plant-derived aromatic compounds.

PMID- 22132096
TI  - Vessel arterial-venous plasticity in adult neovascularization.
AB  - OBJECTIVE: Proper arterial and venous specification is a hallmark of functional
      vascular networks. While arterial-venous identity is genetically pre-determined
      during embryo development, it is unknown whether an analogous pre-specification
      occurs in adult neovascularization. Our goal is to determine whether vessel
      arterial-venous specification in adult neovascularization is pre-determined by
      the identity of the originating vessels. METHODS AND RESULTS: We assessed
      identity specification during neovascularization by implanting isolated
      microvessels of arterial identity from both mice and rats and assessing the
      identity outcomes of the resulting, newly formed vasculature. These microvessels
      of arterial identity spontaneously formed a stereotypical, perfused
      microcirculation comprised of the full complement of microvessel types intrinsic
      to a mature microvasculature. Changes in microvessel identity occurred during
      sprouting angiogenesis, with neovessels displaying an ambiguous arterial-venous
      phenotype associated with reduced EphrinB2 phosphorylation. CONCLUSIONS: Our
      findings indicate that microvessel arterial-venous identity in adult
      neovascularization is not necessarily pre-determined and that adult microvessels
      display a considerable level of phenotypic plasticity during neovascularization.
      In addition, we show that vessels of arterial identity also hold the potential to
      undergo sprouting angiogenesis.

PMID- 22132097
TI  - A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory
      epilepsy, choreoathetosis and learning disability.
AB  - Hydroxysteroid (17beta) dehydrogenase 10 (HSD10) is a mitochondrial
      multifunctional enzyme encoded by the HSD17B10 gene. Missense mutations in this
      gene result in HSD10 deficiency, whereas a silent mutation results in mental
      retardation, X-linked, syndromic 10 (MRXS10). Here we report a novel missense
      mutation found in the HSD17B10 gene, namely c.194T>C transition (rs104886492),
      brought about by the loss of two forked methyl groups of valine 65 in the HSD10
      active site. The affected boy, who possesses mutant HSD10 (p.V65A), has a
      neurological syndrome with metabolic derangements, choreoathetosis, refractory
      epilepsy and learning disability. He has no history of acute decompensation or
      metabolic acidosis whereas his urine organic acid profile, showing elevated
      levels of 2-methyl-3-hydroxybutyrate and tiglylglycine, is characteristic of
      HSD10 deficiency. His HSD10 activity was much lower than the normal control
      level, with normal beta-ketothiolase activity. The c.194T>C mutation in HSD17B10
      can be identified by the restriction fragment polymorphism analysis, thereby
      facilitating the screening of this novel mutation in individuals with
      intellectual disability of unknown etiology and their family members much easier.
      The patient's mother is an asymptomatic carrier, and has a mixed ancestry
      (Hawaiian, Japanese and Chinese). This demonstrates that HSD10 deficiency
      patients are not confined to a particular ethnicity although previously reported
      cases were either Spanish or German descendants.

PMID- 22132098
TI  - An open environment CT-US fusion for tissue segmentation during interventional
      guidance.
AB  - Therapeutic ultrasound (US) can be noninvasively focused to activate drugs,
      ablate tumors and deliver drugs beyond the blood brain barrier. However, well
      controlled guidance of US therapy requires fusion with a navigational modality,
      such as magnetic resonance imaging (MRI) or X-ray computed tomography (CT). Here,
      we developed and validated tissue characterization using a fusion between US and
      CT. The performance of the CT/US fusion was quantified by the calibration error,
      target registration error and fiducial registration error. Met-1 tumors in the
      fat pads of 12 female FVB mice provided a model of developing breast cancer with
      which to evaluate CT-based tissue segmentation. Hounsfield units (HU) within the
      tumor and surrounding fat pad were quantified, validated with histology and
      segmented for parametric analysis (fat: -300 to 0 HU, protein-rich: 1 to 300 HU,
      and bone: HU>300). Our open source CT/US fusion system differentiated soft
      tissue, bone and fat with a spatial accuracy of ~1 mm. Region of interest (ROI)
      analysis of the tumor and surrounding fat pad using a 1 mm(2) ROI resulted in
      mean HU of 68+/-44 within the tumor and -97+/-52 within the fat pad adjacent to
      the tumor (p<0.005). The tumor area measured by CT and histology was correlated
      (r(2) = 0.92), while the area designated as fat decreased with increasing tumor
      size (r(2) = 0.51). Analysis of CT and histology images of the tumor and
      surrounding fat pad revealed an average percentage of fat of 65.3% vs. 75.2%,
      36.5% vs. 48.4%, and 31.6% vs. 38.5% for tumors <75 mm(3), 75-150 mm(3) and >150
      mm(3), respectively. Further, CT mapped bone-soft tissue interfaces near the
      acoustic beam during real-time imaging. Combined CT/US is a feasible method for
      guiding interventions by tracking the acoustic focus within a pre-acquired CT
      image volume and characterizing tissues proximal to and surrounding the acoustic
      focus.

PMID- 22132099
TI  - The protective role of coastal marshes: a systematic review and meta-analysis.
AB  - BACKGROUND: Salt marshes lie between many human communities and the coast and
      have been presumed to protect these communities from coastal hazards by providing
      important ecosystem services. However, previous characterizations of these
      ecosystem services have typically been based on a small number of historical
      studies, and the consistency and extent to which marshes provide these services
      has not been investigated. Here, we review the current evidence for the specific
      processes of wave attenuation, shoreline stabilization and floodwater attenuation
      to determine if and under what conditions salt marshes offer these coastal
      protection services. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a thorough
      search and synthesis of the literature with reference to these processes. Seventy
      five publications met our selection criteria, and we conducted meta-analyses for
      publications with sufficient data available for quantitative analysis. We found
      that combined across all studies (n = 7), salt marsh vegetation had a significant
      positive effect on wave attenuation as measured by reductions in wave height per
      unit distance across marsh vegetation. Salt marsh vegetation also had a
      significant positive effect on shoreline stabilization as measured by accretion,
      lateral erosion reduction, and marsh surface elevation change (n = 30). Salt
      marsh characteristics that were positively correlated to both wave attenuation
      and shoreline stabilization were vegetation density, biomass production, and
      marsh size. Although we could not find studies quantitatively evaluating
      floodwater attenuation within salt marshes, there are several studies noting the
      negative effects of wetland alteration on water quantity regulation within
      coastal areas. CONCLUSIONS/SIGNIFICANCE: Our results show that salt marshes have
      value for coastal hazard mitigation and climate change adaptation. Because we do
      not yet fully understand the magnitude of this value, we propose that decision
      makers employ natural systems to maximize the benefits and ecosystem services
      provided by salt marshes and exercise caution when making decisions that erode
      these services.

PMID- 22132100
TI  - Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients
      failing first-line antiretroviral treatment: a bayesian analysis.
AB  - BACKGROUND: WHO recommends starting therapy with a non-nucleoside reverse
      transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase
      inhibitors (NRTIs), i.e. nevirapine or efavirenz, with lamivudine or
      emtricitabine, plus zidovudine or tenofovir. Few studies have compared resistance
      patterns induced by efavirenz and nevirapine in patients infected with the
      CRF01_AE Southeast Asian HIV-subtype. We compared patterns of NNRTI- and NRTI
      associated mutations in Thai adults failing first-line nevirapine- and efavirenz
      based combinations, using bayesian statistics to optimize use of data. METHODS
      AND FINDINGS: In a treatment cohort of HIV-infected adults on NNRTI-based
      regimens, 119 experienced virologic failure (>500 copies/mL), with resistance
      mutations detected by consensus sequencing. Mutations were analyzed in relation
      to demographic, clinical, and laboratory variables at time of genotyping. The
      Geno2Pheno system was used to evaluate second-line drug options. Eighty-nine
      subjects were on nevirapine and 30 on efavirenz. The NRTI backbone consisted of
      lamivudine or emtricitabine plus either zidovudine (37), stavudine (65), or
      tenofovir (19). The K103N mutation was detected in 83% of patients on efavirenz
      vs. 28% on nevirapine, whereas Y181C was detected in 56% on nevirapine vs. 20%
      efavirenz. M184V was more common with nevirapine (87%) than efavirenz (63%).
      Nevirapine favored TAM-2 resistance pathways whereas efavirenz selected both TAM
      2 and TAM-1 pathways. Emergence of TAM-2 mutations increased with the duration of
      virologic replication (OR 1.25-1.87 per month increment). In zidovudine
      containing regimens, the overall risk of resistance across all drugs was lower
      with nevirapine than with efavirenz, whereas in tenofovir-containing regimen the
      opposite was true. CONCLUSIONS: TAM-2 was the major NRTI resistance pathway for
      CRF01_AE, particularly with nevirapine; it appeared late after virological
      failure. In patients who failed, there appeared to be more second-line drug
      options when zidovudine was combined with nevirapine or tenofovir with efavirenz
      than with alternative combinations.

PMID- 22132102
TI  - Assessment of hypoxia inducible factor levels in cancer cell lines upon hypoxic
      induction using a novel reporter construct.
AB  - Hypoxia Inducible Factor (HIF) signaling pathway is important for tumor cells
      with limited oxygen supplies, as it is shown to be involved in the process of
      proliferation and angiogenesis. Given its pivotal role in cancer biology, robust
      assays for tracking changes in HIF expression are necessary for understanding its
      regulation in cancer as well as developing therapies that target HIF signaling.
      Here we report a novel HIF reporter construct containing tandem repeats of
      minimum HIF binding sites upstream of eYFP coding sequence. We show that the
      reporter construct has an excellent signal to background ratio and the reporter
      activity is HIF dependent and directly correlates with HIF protein levels. By
      utilizing this new construct, we assayed HIF activity levels in different cancer
      cell lines cultured in various degrees of hypoxia. This analysis reveals a
      surprising cancer cell line specific variation of HIF activity in the same level
      of hypoxia. We further show that in two cervical cancer cell lines, ME180 and
      HeLa, the different HIF activity levels observed correlate with the levels of
      hsp90, a cofactor that protects HIF against VHL-independent degradation. This
      novel HIF reporter construct serves as a tool to rapidly define HIF activity
      levels and therefore the therapeutic capacity of potential HIF repressors in
      individual cancers.

PMID- 22132103
TI  - Identification and localization of Myxococcus xanthus porins and lipoproteins.
AB  - Myxococcus xanthus DK1622 contains inner (IM) and outer membranes (OM) separated
      by a peptidoglycan layer. Integral membrane, beta-barrel proteins are found
      exclusively in the OM where they form pores allowing the passage of nutrients,
      waste products and signals. One porin, Oar, is required for intercellular
      communication of the C-signal. An oar mutant produces CsgA but is unable to
      ripple or stimulate csgA mutants to develop suggesting that it is the channel for
      C-signaling. Six prediction programs were evaluated for their ability to identify
      beta-barrel proteins. No program was reliable unless the predicted proteins were
      first parsed using Signal P, Lipo P and TMHMM, after which TMBETA-SVM and
      TMBETADISC-RBF identified beta-barrel proteins most accurately. 228 beta-barrel
      proteins were predicted from among 7331 protein coding regions, representing 3.1%
      of total genes. Sucrose density gradients were used to separate vegetative cell
      IM and OM fractions, and LC-MS/MS of OM proteins identified 54 beta-barrel
      proteins. Another class of membrane proteins, the lipoproteins, are anchored in
      the membrane via a lipid moiety at the N-terminus. 44 OM proteins identified by
      LC-MS/MS were predicted lipoproteins. Lipoproteins are distributed between the
      IM, OM and ECM according to an N-terminal sorting sequence that varies among
      species. Sequence analysis revealed conservation of alanine at the +7 position of
      mature ECM lipoproteins, lysine at the +2 position of IM lipoproteins, and no
      noticable conservation within the OM lipoproteins. Site directed mutagenesis and
      immuno transmission electron microscopy showed that alanine at the +7 position is
      essential for sorting of the lipoprotein FibA into the ECM. FibA appears at
      normal levels in the ECM even when a +2 lysine is added to the signal sequence.
      These results suggest that ECM proteins have a unique method of secretion. It is
      now possible to target lipoproteins to specific IM, OM and ECM locations by
      manipulating the amino acid sequence near the +1 cysteine processing site.

PMID- 22132104
TI  - Reviewing the history of HIV-1: spread of subtype B in the Americas.
AB  - The dispersal of HIV-1 subtype B (HIV-1B) is a reflection of the movement of
      human populations in response to social, political, and geographical issues. The
      initial dissemination of HIV-1B outside Africa seems to have included the passive
      involvement of human populations from the Caribbean in spreading the virus to the
      United States. However, the exact pathways taken during the establishment of the
      pandemic in the Americas remain unclear. Here, we propose a geographical scenario
      for the dissemination of HIV-1B in the Americas, based on phylogenetic and
      genetic statistical analyses of 313 available sequences of the pol gene from 27
      countries. Maximum likelihood and bayesian inference methods were used to explore
      the phylogenetic relationships between HIV-1B sequences, and molecular variance
      estimates were analyzed to infer the genetic structure of the viral population.
      We found that the initial dissemination and subsequent spread of subtype B in the
      Americas occurred via a single introduction event in the Caribbean around 1964
      (1950-1967). Phylogenetic trees present evidence of several primary outbreaks in
      countries in South America, directly seeded by the Caribbean epidemic. Cuba is an
      exception insofar as its epidemic seems to have been introduced from South
      America. One clade comprising isolates from different countries emerged in the
      most-derived branches, reflecting the intense circulation of the virus throughout
      the American continents. Statistical analysis supports the genetic
      compartmentalization of the virus among the Americas, with a close relationship
      between the South American and Caribbean epidemics. These findings reflect the
      complex establishment of the HIV-1B pandemic and contribute to our understanding
      between the migration process of human populations and virus diffusion.

PMID- 22132101
TI  - Bacteria associated with Copestylum (Diptera, Syrphidae) larvae and their cactus
      host Isolatocereus dumortieri.
AB  - We describe the gut bacterial diversity inhabiting two saprophagous syrphids and
      their breeding substrate (decayed tissues of the columnar cactus Isolatocereus
      dumortieri). We analyzed the gut microbiota of Copestylum latum (scooping larvae
      that feed on decayed cactus tissues) and Copestylum limbipenne (whose larvae can
      also feed on semiliquid tissues) using molecular techniques. DNA was extracted
      from larval guts and cactus tissues. The V1-V3 region of the 16S rRNA genes was
      amplified and sequenced. A total of 31,079 sequences were obtained. The main
      findings are: C. limbipenne is dominated by several Enterobacteriaceae, including
      putative nitrogen-fixing genera and pectinolitic species and some denitrifying
      species, whereas in C. latum unclassified Gammaproteobacteria predominate.
      Decayed tissues have a dominant lactic acid bacterial community. The bacterial
      communities were more similar between larval species than between each larva and
      its breeding substrate. The results suggest that the gut bacterial community in
      these insects is not strongly affected by diet and must be dependent on other
      factors, such as vertical transmission, evolutionary history and host innate
      immunity.

PMID- 22132105
TI  - Capacity-speed relationships in prefrontal cortex.
AB  - Working memory (WM) capacity and WM processing speed are simple cognitive
      measures that underlie human performance in complex processes such as reasoning
      and language comprehension. These cognitive measures have shown to be
      interrelated in behavioral studies, yet the neural mechanism behind this
      interdependence has not been elucidated. We have carried out two functional MRI
      studies to separately identify brain regions involved in capacity and speed.
      Experiment 1, using a block-design WM verbal task, identified increased WM
      capacity with increased activity in right prefrontal regions, and Experiment 2,
      using a single-trial WM verbal task, identified increased WM processing speed
      with increased activity in similar regions. Our results suggest that right
      prefrontal areas may be a common region interlinking these two cognitive
      measures. Moreover, an overlap analysis with regions associated with binding or
      chunking suggest that this strategic memory consolidation process may be the
      mechanism interlinking WM capacity and WM speed.

PMID- 22132106
TI  - Activation of Ras requires the ERM-dependent link of actin to the plasma
      membrane.
AB  - BACKGROUND: Receptor tyrosine kinases (RTKs) participate in a multitude of
      signaling pathways, some of them via the small G-protein Ras. An important
      component in the activation of Ras is Son of sevenless (SOS), which catalyzes the
      nucleotide exchange on Ras. PRINCIPAL FINDINGS: We can now demonstrate that the
      activation of Ras requires, in addition, the essential participation of ezrin,
      radixin and/or moesin (ERM), a family of actin-binding proteins, and of actin.
      Disrupting either the interaction of the ERM proteins with co-receptors, down
      regulation of ERM proteins by siRNA, expression of dominant-negative mutants of
      the ERM proteins or disruption of F-actin, abolishes growth factor-induced Ras
      activation. Ezrin/actin catalyzes the formation of a multiprotein complex
      consisting of RTK, co-receptor, Grb2, SOS and Ras. We also identify binding sites
      for both Ras and SOS on ezrin; mutations of these binding sites destroy the
      interactions and inhibit Ras activation. Finally, we show that the formation of
      the ezrin-dependent complex is necessary to enhance the catalytic activity of SOS
      and thereby Ras activation. CONCLUSIONS: Taking these findings together, we
      propose that the ERM proteins are novel scaffolds at the level of SOS activity
      control, which is relevant for both normal Ras function and dysfunction known to
      occur in several human cancers.

PMID- 22132107
TI  - Which compound to select in lead optimization? Prospectively validated
      proteochemometric models guide preclinical development.
AB  - In quite a few diseases, drug resistance due to target variability poses a
      serious problem in pharmacotherapy. This is certainly true for HIV, and hence, it
      is often unknown which drug is best to use or to develop against an individual
      HIV strain. In this work we applied 'proteochemometric' modeling of HIV Non
      Nucleoside Reverse Transcriptase (NNRTI) inhibitors to support preclinical
      development by predicting compound performance on multiple mutants in the lead
      selection stage. Proteochemometric models are based on both small molecule and
      target properties and can thus capture multi-target activity relationships
      simultaneously, the targets in this case being a set of 14 HIV Reverse
      Transcriptase (RT) mutants. We validated our model by experimentally confirming
      model predictions for 317 untested compound-mutant pairs, with a prediction error
      comparable with assay variability (RMSE 0.62). Furthermore, dependent on the
      similarity of a new mutant to the training set, we could predict with high
      accuracy which compound will be most effective on a sequence with a previously
      unknown genotype. Hence, our models allow the evaluation of compound performance
      on untested sequences and the selection of the most promising leads for further
      preclinical research. The modeling concept is likely to be applicable also to
      other target families with genetic variability like other viruses or bacteria, or
      with similar orthologs like GPCRs.

PMID- 22132108
TI  - Assessing the utility of photoswitchable fluorescent proteins for tracking
      intercellular protein movement in the Arabidopsis root.
AB  - One way in which cells communicate is through the direct transfer of proteins. In
      plants, many of these proteins are transcription factors, which are made by one
      cell type and traffic into another. In order to understand how this movement
      occurs and its role in development, we would like to track this movement in live,
      intact plants in real-time. Here we examine the utility of the photoconvertible
      proteins, Dendra2 and (to a lesser extent) EosFP as tags for studying
      intracellular and intercellular protein movement in the Arabidopsis root. To this
      end, we made fusions between Dendra2 and six mobile transcription factors. Our
      results show that Dendra2 is an effective tool for studying protein movement
      between plant cells. Interestingly, we found that Dendra2 could not simply be
      swapped into existing constructs that had originally contained GFP. Most of the
      fusions made in this way failed to produce a fluorescent fusion. In addition we
      found that the optimal settings for photoconversion of Dendra2 in stably
      transformed roots were different from what has been published for photoconversion
      in transient assays in plants or in animal cells. By modifying the confocal
      setting, we were able to photoconvert Dendra2 in all cell layers in the root.
      However the efficiency of photoconversion was affected by the position of the
      cell layer within the root, with more internal tissues requiring more energy. By
      examining the Dendra2 fusions, we confirmed the mobility of the SHORT-ROOT (SHR)
      and CAPRICE (CPC) transcription factors between cells and we further discovered
      that SHR movement in stele and CPC movement in the epidermis are non-directional.

PMID- 22132109
TI  - Characterization of a weak allele of zebrafish cloche mutant.
AB  - Hematopoiesis is a complicated and dynamic process about which the molecular
      mechanisms remain poorly understood. Danio rerio (zebrafish) is an excellent
      vertebrate system for studying hematopoiesis and developmental mechanisms. In the
      previous study, we isolated and identified a cloche(172) (clo(172)) mutant, a
      novel allele compared to the original cloche (clo) mutant, through using
      complementation test and initial mapping. Here, according to whole mount in-situ
      hybridization, we report that the endothelial cells in clo(172) mutant embryos,
      although initially developed, failed to form the functional vascular system
      eventually. In addition, further characterization indicates that the clo(172)
      mutant exhibited weaker defects instead of completely lost in primitive erythroid
      cells and definitive hematopoietic cells compared with the clo(s5) mutant. In
      contrast, primitive myeloid cells were totally lost in clo(172) mutant.
      Furthermore, these reappeared definitive myeloid cells were demonstrated to
      initiate from the remaining hematopoietic stem cells (HSCs) in clo(172) mutant,
      confirmed by the dramatic decrease of lyc in clo(172)runx1(w84x) double mutant.
      Collectively, the clo(172) mutant is a weak allele compared to the clo(s5)
      mutant, therefore providing a model for studying the early development of
      hematopoietic and vascular system, as well as an opportunity to further
      understand the function of the cloche gene.

PMID- 22132110
TI  - Crosstalk between integrin alphavbeta3 and estrogen receptor-alpha is involved in
      thyroid hormone-induced proliferation in human lung carcinoma cells.
AB  - A cell surface receptor for thyroid hormone that activates extracellular
      regulated kinase (ERK) 1/2 has been identified on integrin alphavbeta3. We have
      examined the actions of thyroid hormone initiated at the integrin on human NCI
      H522 non-small cell lung carcinoma and NCI-H510A small cell lung cancer cells. At
      a physiologic total hormone concentration (10(-7) M), T(4) significantly
      increased proliferating cell nuclear antigen (PCNA) abundance in these cell
      lines, as did 3, 5, 3'-triiodo-L-thyronine (T(3)) at a supraphysiologic
      concentration. Neutralizing antibody to integrin alphavbeta3 and an integrin
      binding Arg-Gly-Asp (RGD) peptide blocked thyroid hormone-induced PCNA
      expression. Tetraiodothyroacetic acid (tetrac) lacks thyroid hormone function but
      inhibits binding of T(4) and T(3) to the integrin receptor; tetrac eliminated
      thyroid hormone-induced lung cancer cell proliferation and ERK1/2 activation. In
      these estrogen receptor-alpha (ERalpha)-positive lung cancer cells, thyroid
      hormone (T(4)>T(3)) caused phosphorylation of ERalpha; the specific ERalpha
      antagonist ICI 182,780 blocked T(4)-induced, but not T(3)-induced ERK1/2
      activation, as well as ERalpha phosphorylation, proliferating-cell nuclear
      antigen (PCNA) expression and hormone-dependent thymidine uptake by tumor cells.
      Thus, in ERalpha-positive human lung cancer cells, the proliferative action of
      thyroid hormone initiated at the plasma membrane is at least in part mediated by
      ERalpha. In summary, thyroid hormone may be one of several endogenous factors
      capable of supporting proliferation of lung cancer cells. Activity as an
      inhibitor of lung cancer cell proliferation induced at the integrin receptor
      makes tetrac a novel anti-proliferative agent.

PMID- 22132111
TI  - In vitro grown sheep preantral follicles yield oocytes with normal nuclear
      epigenetic maturation.
AB  - BACKGROUND: Assisted reproductive technologies allow to utilize a limited number
      of fully grown oocytes despite the presence in the ovary of a large pool of
      meiotically incompetent gametes potentially able to produce live births. In vitro
      folliculogenesis could be useful to recruit these oocytes by promoting their
      growth and differentiation. METHODOLOGY/PRINCIPAL FINDINGS: In vitro
      folliculogenesis was performed starting from sheep preantral (PA) follicles to
      evaluate oocyte nuclear/epigenetic maturation. Chromatin configuration,
      quantification of global DNA methylation, and epigenetic remodelling enzymes were
      evaluated with immunocytochemistry, telomere elongation was assessed with the Q
      FISH technique, while the DNA methylation status at the DMRs of maternally IGF2R
      and BEGAIN, and paternally H19 methylated imprinted genes was determined by
      bisulfite sequencing and COBRA. Specifically, 70% of PA underwent early antrum
      (EA) differentiation and supported in culture oocyte global DNA methylation,
      telomere elongation, TERT and Dnmt3a redistribution thus mimicking the
      physiological events that involve the oocyte during the transition from secondary
      to tertiary follicle. Dnmt1 anticipated cytoplasmic translocation in in vitro
      grown oocytes did not impair global and single gene DNA methylation. Indeed, the
      in vitro grown oocytes acquired a methylation profile of IGF2R and BEGAIN
      compatible with the follicle/oocyte stage reached, and maintained an unmethylated
      status of H19. In addition, the percentage of oocytes displaying a condensed
      chromatin configuration resulted lower in in vitro grown oocytes, however, their
      ability to undergo meiosis and early embryo development after IVF and
      parthenogenetic activation was similar to that recorded in EA follicle in vivo
      grown oocytes. CONCLUSIONS/SIGNIFICANCE: In conclusion, the in vitro
      folliculogenesis was able to support the intracellular/nuclear mechanisms leading
      the oocytes to acquire a meiotic and developmental competence. Thus, the in vitro
      culture may increase the availability of fertilizable oocytes in sheep, and
      become an in vitro translational model to investigate the mechanisms governing
      nuclear/epigenetic oocyte maturation.

PMID- 22132112
TI  - The bacterial nanorecorder: engineering E. coli to function as a chemical
      recording device.
AB  - Synthetic biology is an emerging branch of molecular biology that uses synthetic
      genetic constructs to create man-made cells or organisms that are capable of
      performing novel and/or useful applications. Using a synthetic chemically
      sensitive genetic toggle switch to activate appropriate fluorescent protein
      indicators (GFP, RFP) and a cell division inhibitor (minC), we have created a
      novel E. coli strain that can be used as a highly specific, yet simple and
      inexpensive chemical recording device. This biological "nanorecorder" can be used
      to determine both the type and the time at which a brief chemical exposure event
      has occurred. In particular, we show that the short-term exposure (15-30 min) of
      cells harboring this synthetic genetic circuit to small molecule signals
      (anhydrotetracycline or IPTG) triggered long-term and uniform cell elongation,
      with cell length being directly proportional to the time elapsed following a
      brief chemical exposure. This work demonstrates that facile modification of an
      existing genetic toggle switch can be exploited to generate a robust,
      biologically-based "nanorecorder" that could potentially be adapted to detect,
      respond and record a wide range of chemical stimuli that may vary over time and
      space.

PMID- 22132113
TI  - Acupuncture enhances the synaptic dopamine availability to improve motor function
      in a mouse model of Parkinson's disease.
AB  - Parkinson's disease (PD) is caused by the selective loss of dopaminergic neurons
      in the substantia nigra (SN) and the depletion of striatal dopamine (DA).
      Acupuncture, as an alternative therapy for PD, has beneficial effects in both PD
      patients and PD animal models, although the underlying mechanisms therein remain
      uncertain. The present study investigated whether acupuncture treatment affected
      dopamine neurotransmission in a PD mouse model using 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). We found that acupuncture treatment at acupoint GB34
      improved motor function with accompanying dopaminergic neuron protection against
      MPTP but did not restore striatal dopamine depletion. Instead, acupuncture
      treatment increased dopamine release that in turn, may lead to the enhancement of
      dopamine availability in the synaptic cleft. Moreover, acupuncture treatment
      mitigated MPTP-induced abnormal postsynaptic changes, suggesting that acupuncture
      treatment may increase postsynaptic dopamine neurotransmission and facilitate the
      normalization of basal ganglia activity. These results suggest that the
      acupuncture-induced enhancement of synaptic dopamine availability may play a
      critical role in motor function improvement against MPTP.

PMID- 22132114
TI  - Proteomics portrait of archival lesions of chronic pancreatitis.
AB  - Chronic pancreatitis is a chronic inflammatory disorder of the pancreas. The
      etiology is multi-fold, but all lead to progressive scarring and loss of
      pancreatic function. Early diagnosis is difficult; and the understanding of the
      molecular events that underlie this progressive disease is limited. In this
      study, we investigated differential proteins associated with mild and severe
      chronic pancreatitis in comparison with normal pancreas and pancreatic cancer.
      Paraffin-embedded formalin-fixed tissues from five well-characterized specimens
      each of normal pancreas (NL), mild chronic pancreatitis (MCP), severe chronic
      pancreatitis (SCP) and pancreatic ductal adenocarcinoma (PDAC) were subjected to
      proteomic analysis using a "label-free" comparative approach. Our results show
      that the numbers of differential proteins increase substantially with the disease
      severity, from mild to severe chronic pancreatitis, while the number of
      dysregulated proteins is highest in pancreatic adenocarcinoma. Important
      functional groups and biological processes associated with chronic pancreatitis
      and cancer include acinar cell secretory proteins, pancreatic fibrosis/stellate
      cell activation, glycoproteins, and inflammatory proteins. Three differential
      proteins were selected for verification by immunohistochemistry, including
      collagen 14A1, lumican and versican. Further canonical pathway analysis revealed
      that acute phase response signal, prothrombin activation pathway, and pancreatic
      fibrosis/pancreatic stellate cell activation pathway were the most significant
      pathways involved in chronic pancreatitis, while pathways relating to metabolism
      were the most significant pathways in pancreatic adenocarcinoma. Our study
      reveals a group of differentially expressed proteins and the related pathways
      that may shed light on the pathogenesis of chronic pancreatitis and the common
      molecular events associated with chronic pancreatitis and pancreatic
      adenocarcinoma.

PMID- 22132115
TI  - Deficient spindle assembly checkpoint in multiple myeloma.
AB  - Multiple myeloma (MM) is a hematological disease characterized by an abnormal
      accumulation of plasma cells in the bone marrow. These cells have frequent
      cytogenetic abnormalities including translocations of the immunoglobulin heavy
      chain gene and chromosomal gains and losses. In fact, a singular characteristic
      differentiating MM from other hematological malignancies is the presence of a
      high degree of aneuploidies. As chromosomal abnormalities can be generated by
      alterations in the spindle assembly checkpoint (SAC), the functionality of such
      checkpoint was tested in MM. When SAC components were analyzed in MM cell lines,
      the RNA levels of most of them were conserved. Nevertheless, the protein content
      of some key constituents was very low in several cell lines, as was the case of
      MAD2 or CDC20 in RPMI-8226 or RPMI-LR5 cells. The recovery of their cellular
      content did not substantially affect cell growth, but improved their ability to
      segregate chromosomes. Finally, SAC functionality was tested by challenging cells
      with agents disrupting microtubule dynamics. Most of the cell lines analyzed
      exhibited functional defects in this checkpoint. Based on the data obtained,
      alterations both in SAC components and their functionality have been detected in
      MM, pointing to this pathway as a potential target in MM treatment.

PMID- 22132116
TI  - Inotropic action of the puberty hormone kisspeptin in rat, mouse and human:
      cardiovascular distribution and characteristics of the kisspeptin receptor.
AB  - Kisspeptins, the ligands of the kisspeptin receptor known for its roles in
      reproduction and cancer, are also vasoconstrictor peptides in atherosclerosis
      prone human aorta and coronary artery. The aim of this study was to further
      investigate the cardiovascular localisation and function of the kisspeptins and
      their receptor in human compared to rat and mouse heart. Immunohistochemistry and
      radioligand binding techniques were employed to investigate kisspeptin receptor
      localisation, density and pharmacological characteristics in cardiac tissues from
      all three species. Radioimmunoassay was used to detect kisspeptin peptide levels
      in human normal heart and to identify any pathological changes in myocardium from
      patients transplanted for cardiomyopathy or ischaemic heart disease. The cardiac
      function of kisspeptin receptor was studied in isolated human, rat and mouse
      paced atria, with a role for the receptor confirmed using mice with targeted
      disruption of Kiss1r. The data demonstrated that kisspeptin receptor-like
      immunoreactivity localised to endothelial and smooth muscle cells of
      intramyocardial blood vessels and to myocytes in human and rodent tissue.
      [(125)I]KP-14 bound saturably, with subnanomolar affinity to human and rodent
      myocardium (K(D) = 0.12 nM, human; K(D) = 0.44 nM, rat). Positive inotropic
      effects of kisspeptin were observed in rat, human and mouse. No response was
      observed in mice with targeted disruption of Kiss1r. In human heart a decrease in
      cardiac kisspeptin level was detected in ischaemic heart disease. Kisspeptin and
      its receptor are expressed in the human, rat and mouse heart and kisspeptins
      possess potent positive inotropic activity. The cardiovascular actions of the
      kisspeptins may contribute to the role of these peptides in pregnancy but the
      consequences of receptor activation must be considered if kisspeptin receptor
      agonists are developed for use in the treatment of reproductive disorders or
      cancer.

PMID- 22132118
TI  - Crowd intelligence for the classification of fractures and beyond.
AB  - BACKGROUND: Medical diagnosis, like all products of human cognition, is subject
      to error. We tested the hypothesis that errors of diagnosis in the realm of
      fracture classification can be reduced by a consensus (group) diagnosis; and that
      digital imaging and Internet access makes feasible the compilation of a
      diagnostic consensus in real time. METHODS: Twelve orthopaedic surgeons were
      asked to evaluate 20 hip radiographs demonstrating a femoral neck fracture. The
      surgeons were asked to determine if the fractures were displaced or not. Because
      no reference standard is available, the maximal accuracy of the diagnosis of
      displacement can be inferred from inter-observer reliability: if two readers
      disagree about displacement, one of them must be wrong. That method was employed
      here. Additionally, virtual reader groups of 3 and 5 individual members were
      amalgamated, with the response of those groups defined by majority vote. The
      purpose of this step was to see if increasing the number of readers would improve
      accuracy. In a second experiment, to study the feasibility of amassing a reader
      group on the Internet in real time, 40 volunteers were sent 10 periodic email
      requests to answer questions and their response times were assessed. RESULTS: The
      mean kappa coefficient for individual inter-observer reliability for the
      diagnosis of displacement was 0.69, comparable to prior published values. For 3
      member virtual reader groups, inter-observer reliability was 0.77; and for 5
      member groups, it was 0.80. In the experiment studying the feasibility of
      amassing a reader group in real time, the mean response time was 594 minutes. For
      all cases, a 9-member group (theoretically 99% accurate) was amassed in 135.8
      minutes or less. CONCLUSIONS: Consensus may improve diagnosis. Amassing a group
      for this purpose on the Internet is feasible.

PMID- 22132117
TI  - Lithium monotherapy increases ACTH and cortisol response in the DEX/CRH test in
      unipolar depressed subjects. A study with 30 treatment-naive patients.
AB  - BACKGROUND: Distorted activity of the hypothalamic-pituitary-adrenocortical (HPA)
      system is one of the most robustly documented biological abnormalities in major
      depression. Lithium is central to the treatment of affective disorders, but
      little is known about its effects on the HPA system of depressed subjects.
      OBJECTIVE: To assess the effects of lithium monotherapy on the HPA system of
      patients with major depression by means of the combined DEX/CRH test. METHOD:
      Thirty drug-naive outpatients with major depression (single episode or unipolar
      recurrent; SCID I- and II-confirmed) were treated with lithium monotherapy for
      four weeks. The DEX/CRH test was conducted directly before intake of the first
      lithium tablet and four weeks thereafter. Weekly ratings with the HDRS(21) were
      used to determine response (>=50% symptom reduction) and remission (HDRS <=7).
      RESULTS: Lithium levels within the therapeutic range were achieved rapidly.
      Tolerability was good; no patient terminated the treatment prematurely. Response
      and remission rates were 50% and 33% respectively. Compared to the DEX/CRH test
      before the start of the treatment, a considerable and significant increase in all
      CRH-stimulated ACTH and cortisol parameters could be detected in the second
      DEX/CRH test. When analysed with particular regard to responders and non
      responders, that significant increase was only present in the responders.
      CONCLUSIONS: We were able to demonstrate that lithium leads to a significant
      activation of the HPA system. This is possibly connected to stimulation of
      hypothalamic arginine vasoporessin (AVP), to direct intracellular effects of
      lithium on pituitary cells and to an induction of gene expression. TRIAL
      REGISTRATION: drks-nue.uniklinik-freiburg.de DRKS00003185.

PMID- 22132119
TI  - Abnormal notochord branching is associated with foregut malformations in the
      adriamycin treated mouse model.
AB  - Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively
      common human congenital malformations of the foregut where the oesophagus does
      not connect with the stomach and there is an abnormal connection between the
      stomach and the respiratory tract. They require immediate corrective surgery and
      have an impact on the future health of the individual. These abnormalities are
      mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin.
      The causes of OA/TOF during human development are not known, however a number of
      mouse mutants where different signalling pathways are directly affected, show
      similar abnormalities, implicating multiple and complex signalling mechanisms.
      The similarities in developmental outcome seen in human infants and in the
      adriamycin treated mouse model underline the potential of this model to unravel
      the early embryological events and further our understanding of the processes
      disturbed, leading to such abnormalities. Here we report a systematic study of
      the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8
      and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We
      describe a spectrum of 8 defects, the most common of which is ventral
      displacement and branching of the notochord (in 94% of embryos at E10) and a
      close spatial correspondence between the site of notochord branching and defects
      of the foregut. In addition gene expression analysis shows altered dorso-ventral
      foregut patterning in the vicinity of notochord branches. This study shows a
      number of features of the adriamycin mouse model not previously reported,
      implicates the notochord as a primary site of disturbance in such abnormalities
      and underlines the importance of the model to further address the mechanistic
      basis of foregut congenital abnormalities.

PMID- 22132120
TI  - Natural killer cell mediated missing-self recognition can protect mice from
      primary chronic myeloid leukemia in vivo.
AB  - BACKGROUND: Natural Killer (NK) cells are thought to protect from residual
      leukemic cells in patients receiving stem cell transplantation. However, multiple
      retrospective analyses of patient data have yielded conflicting conclusions
      regarding a putative role of NK cells and the essential NK cell recognition
      events mediating a protective effect against leukemia. Further, a NK cell
      mediated protective effect against primary leukemia in vivo has not been shown
      directly. METHODOLOGY/PRINCIPAL FINDINGS: Here we addressed whether NK cells have
      the potential to control chronic myeloid leukemia (CML) arising based on the
      transplantation of BCR-ABL1 oncogene expressing primary bone marrow precursor
      cells into lethally irradiated recipient mice. These analyses identified missing
      self recognition as the only NK cell-mediated recognition strategy, which is able
      to significantly protect from the development of CML disease in vivo. CONCLUSION:
      Our data provide a proof of principle that NK cells can control primary leukemic
      cells in vivo. Since the presence of NK cells reduced the abundance of leukemia
      propagating cancer stem cells, the data raise the possibility that NK cell
      recognition has the potential to cure CML, which may be difficult using small
      molecule BCR-ABL1 inhibitors. Finally, our findings validate approaches to treat
      leukemia using antibody-based blockade of self-specific inhibitory MHC class I
      receptors.

PMID- 22132121
TI  - Hypochlorous acid-induced heme degradation from lactoperoxidase as a novel
      mechanism of free iron release and tissue injury in inflammatory diseases.
AB  - Lactoperoxidase (LPO) is the major consumer of hydrogen peroxide (H(2)O(2)) in
      the airways through its ability to oxidize thiocyanate (SCN(-)) to produce
      hypothiocyanous acid, an antimicrobial agent. In nasal inflammatory diseases,
      such as cystic fibrosis, both LPO and myeloperoxidase (MPO), another mammalian
      peroxidase secreted by neutrophils, are known to co-localize. The aim of this
      study was to assess the interaction of LPO and hypochlorous acid (HOCl), the
      final product of MPO. Our rapid kinetic measurements revealed that HOCl binds
      rapidly and reversibly to LPO-Fe(III) to form the LPO-Fe(III)-OCl complex, which
      in turn decayed irreversibly to LPO Compound II through the formation of Compound
      I. The decay rate constant of Compound II decreased with increasing HOCl
      concentration with an inflection point at 100 uM HOCl, after which the decay rate
      increased. This point of inflection is the critical concentration of HOCl beyond
      which HOCl switches its role, from mediating destabilization of LPO Compound II
      to LPO heme destruction. Lactoperoxidase heme destruction was associated with
      protein aggregation, free iron release, and formation of a number of fluorescent
      heme degradation products. Similar results were obtained when LPO-Fe(II)-O(2),
      Compound III, was exposed to HOCl. Heme destruction can be partially or
      completely prevented in the presence of SCN(-). On the basis of the present
      results we concluded that a complex bi-directional relationship exists between
      LPO activity and HOCl levels at sites of inflammation; LPO serve as a catalytic
      sink for HOCl, while HOCl serves to modulate LPO catalytic activity,
      bioavailability, and function.

PMID- 22132123
TI  - Radioisotopes demonstrate the contrasting bioaccumulation capacities of heavy
      metals in embryonic stages of cephalopod species.
AB  - Cephalopods play a key role in many marine trophic food webs and also constitute
      alternative fishery resources in the context of the ongoing decline in finfish
      stocks. Most coastal cephalopod species of commercial importance migrate into
      shallow waters during the breeding season to lay their eggs, and are consequently
      subjected to coastal contamination. Eggs of common cuttlefish Sepia officinalis,
      European squid Loligo vulgaris, common octopus Octopus vulgaris and the sepiolid
      Rossia macrosoma were exposed during embryonic development to dissolved (110m)Ag,
      (109)Cd, (60)Co, (54)Mn and (65)Zn in order to determine their metal accumulation
      efficiencies and distribution among different egg compartments. Cuttlefish eggs,
      in which hard shells enclose the embryos, showed the lowest concentration factor
      (CF) values despite a longer duration of exposure. In contrast, octopus eggs,
      which are only protected by the chorionic membrane, accumulated the most metal.
      Uptake appears to be linked to the selective retention properties of the egg
      envelopes with respect to each element. The study also demonstrated that the
      octopus embryo accumulated (110m)Ag directly from the dissolved phase and also
      indirectly through assimilation of the contaminated yolk. These results raise
      questions regarding the potential contrasting vulnerability of early life stages
      of cephalopods to the metallic contamination of coastal waters.

PMID- 22132122
TI  - The microRNA-processing enzyme Dicer is essential for thyroid function.
AB  - Dicer is a type III ribonuclease required for the biogenesis of microRNAs
      (miRNAs), a class of small non-coding RNAs regulating gene expression at the post
      transcriptional level. To explore the functional role of miRNAs in thyroid gland
      function, we generated a thyrocyte-specific Dicer conditional knockout mouse.
      Here we show that development and early differentiation of the thyroid gland are
      not affected by the absence of Dicer, while severe hypothyroidism gradually
      develops after birth, leading to reduced body weight and shortened life span.
      Histological and molecular characterization of knockout mice reveals a dramatic
      loss of the thyroid gland follicular architecture associated with functional
      aberrations and down-regulation of several differentiation markers. The data
      presented in this study show for the first time that an intact miRNAs processing
      machinery is essential for thyroid physiology, suggesting that deregulation of
      specific miRNAs could be also involved in human thyroid dysfunctions.

PMID- 22132124
TI  - Evidence that obesity risk factor potencies are weight dependent, a phenomenon
      that may explain accelerated weight gain in western societies.
AB  - BACKGROUND: We have shown that individuals at the highest percentiles of the body
      mass index (BMI) distribution (i.e., most overweight) experience greater
      increases in body weight from sedentary lifestyle than those from the lowest
      percentiles. The purpose of the current analyses was to assess whether recent,
      accelerated increases in obesity could potentially be due to increased
      vulnerability to obesity risk factors as the population has become more
      overweight. METHODOLOGY/PRINCIPAL FINDINGS: Quantile regression was used to
      compare BMI population percentiles to obesity risk factors (lower education,
      diets characterized by high-meat/low-fruit content, parental adiposity) in two
      independent samples of men (N(1) = 3,513, N(2) = 11,365) and women (N(1) =
      15,809, N(2) = 10,159). The samples were subsets of the National Walkers' (Study
      1) and Runners' (Study 2) Health Studies whose physical activities fell short of
      nationally recommended activity levels. The data were adjusted for age, race, and
      any residual effects of physical activity. The regression slopes for BMI vs.
      education, diet, and family history became progressively stronger from the lowest
      (e.g., 5(th), 6(th)...) to the highest (e.g., ..., 94(th), 95(th)) BMI
      percentiles. Compared to the 10(th) BMI percentile, their effects on the 90(th)
      BMI percentile were: 1) 2.7- to 8.6-fold greater in women and 2.0- to 2.4-fold
      greater in men for education; 2) 3.6- to 4.8-fold greater in women and 1.7- to
      2.7-fold greater in men for diet; and 3) 2.0- to 2.6-fold greater in women and
      1.7-fold greater in men for family history. CONCLUSIONS/SIGNIFICANCE: Thus we
      propose risk factors that produce little weight gain in lean individuals may
      become more potent with increasing adiposity. This leads us to hypothesize that
      an individual's obesity is itself a major component of their obesogenic
      environment, and that, the cycle of weight gain and increased sensitivity to
      obesity risk factors may partly explain recent increases in obesity in western
      societies.

PMID- 22132125
TI  - Moving away from nasty encounters enhances cooperation in ecological prisoner's
      dilemma game.
AB  - We study the role of migration in the evolution of cooperation. Individuals
      spatially located on a square lattice play the prisoner's dilemma game.
      Dissatisfied players, who have been exploited by defectors, tend to terminate
      interaction with selfish partners by leaving the current habitats, and explore
      unknown physical niches available surrounding them. The time scale ratio of game
      interaction to natural selection governs how many game rounds occur before
      individuals experience strategy updating. Under local migration and strong
      selection, simulation results demonstrate that cooperation can be stabilized for
      a wide range of model parameters, and the slower the natural selection, the more
      favorable for the emergence of cooperation. Besides, how the selection intensity
      affects cooperators' evolutionary fate is also investigated. We find that
      increasing it weakens cooperators' viability at different speeds for different
      time scale ratios. However, cooperation is greatly improved provided that
      individuals are offered with enough chance to agglomerate, while cooperation can
      always establish under weak selection but vanishes under very strong selection
      whenever individuals have less odds to migrate. Whenever the migration range
      restriction is removed, the parameter area responsible for the emergence of
      cooperation is, albeit somewhat compressed, still remarkable, validating the
      effectiveness of collectively migrating in promoting cooperation.

PMID- 22132126
TI  - Prevalence of antidepressant prescription or use in patients with acute coronary
      syndrome: a systematic review.
AB  - BACKGROUND AND OBJECTIVES: Depression is common among acute coronary syndrome
      (ACS) patients and is associated with poor prognosis. Cardiac side effects of
      older antidepressants were well-known, but newer antidepressants are generally
      thought of as safe to use in patients with heart disease. The objective was to
      assess rates of antidepressant use or prescription to patients within a year of
      an ACS. METHODS: PubMed, PsycINFO, and CINAHL databases searched through May 29,
      2009; manual searching of 33 journals from May 2009 to September 2010. Articles
      in any language were included if they reported point or period prevalence of
      antidepressant use or prescription in the 12 months prior or subsequent to an ACS
      for >=100 patients. Two investigators independently selected studies for
      inclusion/exclusion and extracted methodological characteristics and outcomes
      from included studies (study setting, inclusion/exclusion criteria, sample size,
      prevalence of antidepressant prescription/use, method of assessing antidepressant
      prescription/use, time period of assessment). RESULTS: A total of 24 articles
      were included. The majority were from North America and Europe, and most utilized
      chart review or self-report to assess antidepressant use or prescription.
      Although there was substantial heterogeneity in results, overall, rates of
      antidepressant use or prescription increased from less than 5% prior to 1995 to
      10-15% after 2000. In general, studies from North America reported substantially
      higher rates than studies from Europe, approximately 5% higher among studies that
      used chart or self-report data. CONCLUSIONS: Antidepressant use or prescription
      has increased considerably, and by 2005 approximately 10% to 15% of ACS patients
      were prescribed or using one of these drugs.

PMID- 22132127
TI  - Chromosome isolation by flow sorting in Aegilops umbellulata and Ae. comosa and
      their allotetraploid hybrids Ae. biuncialis and Ae. geniculata.
AB  - This study evaluates the potential of flow cytometry for chromosome sorting in
      two wild diploid wheats Aegilops umbellulata and Ae. comosa and their natural
      allotetraploid hybrids Ae. biuncialis and Ae. geniculata. Flow karyotypes
      obtained after the analysis of DAPI-stained chromosomes were characterized and
      content of chromosome peaks was determined. Peaks of chromosome 1U could be
      discriminated in flow karyotypes of Ae. umbellulata and Ae. biuncialis and the
      chromosome could be sorted with purities exceeding 95%. The remaining chromosomes
      formed composite peaks and could be sorted in groups of two to four. Twenty four
      wheat SSR markers were tested for their position on chromosomes of Ae.
      umbellulata and Ae. comosa using PCR on DNA amplified from flow-sorted
      chromosomes and genomic DNA of wheat-Ae. geniculata addition lines, respectively.
      Six SSR markers were located on particular Aegilops chromosomes using sorted
      chromosomes, thus confirming the usefulness of this approach for physical
      mapping. The SSR markers are suitable for marker assisted selection of wheat
      Aegilops introgression lines. The results obtained in this work provide new
      opportunities for dissecting genomes of wild relatives of wheat with the aim to
      assist in alien gene transfer and discovery of novel genes for wheat improvement.

PMID- 22132128
TI  - Non-invasive epigenetic detection of fetal trisomy 21 in first trimester maternal
      plasma.
AB  - BACKGROUND: Down syndrome (DS) is the most common known aneuploidy, caused by an
      extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers
      have been investigated for non-invasive prenatal detection of fetal DS. The
      phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely
      methylated in blood (M-PDE9A) and unmethylated in the placenta (U-PDE9A).
      Therefore, we estimated the accuracy of non-invasive fetal DS detection during
      the first trimester of pregnancy using this tissue-specific epigenetic
      characteristic of PDE9A. METHODOLOGY/PRINCIPAL FINDINGS: A nested, case-control
      study was conducted using maternal plasma samples collected from 108 pregnant
      women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls
      according to gestational weeks at blood sampling). All pregnancies were
      singletons at or before 12 weeks of gestation between October 2008 and May 2009.
      The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative
      methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were
      obtained in all samples and did not differ between male and female fetuses. M
      PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5
      copies/mL; P = 0.928). U-PDE9A levels were significantly elevated in women with
      DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001). The
      sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non
      invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false
      positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U
      PDE9A level and UI were 46.2 [95% confidence interval: 7.8-151.6] and 63.7 [95%
      confidence interval: 23.2-206.7], respectively. CONCLUSIONS: Our findings suggest
      that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers
      for non-invasive fetal DS detection during the first trimester of pregnancy,
      regardless of fetal gender.

PMID- 22132129
TI  - Impact of meat consumption, preparation, and mutagens on aggressive prostate
      cancer.
AB  - BACKGROUND: The association between meat consumption and prostate cancer remains
      unclear, perhaps reflecting heterogeneity in the types of tumors studied and the
      method of meat preparation--which can impact the production of carcinogens.
      METHODS: We address both issues in this case-control study focused on aggressive
      prostate cancer (470 cases and 512 controls), where men reported not only their
      meat intake but also their meat preparation and doneness level on a semi
      quantitative food-frequency questionnaire. Associations between overall and
      grilled meat consumption, doneness level, ensuing carcinogens and aggressive
      prostate cancer were assessed using multivariate logistic regression. RESULTS:
      Higher consumption of any ground beef or processed meats were positively
      associated with aggressive prostate cancer, with ground beef showing the
      strongest association (OR = 2.30, 95% CI:1.39-3.81; P-trend = 0.002). This
      association primarily reflected intake of grilled or barbequed meat, with more
      well-done meat conferring a higher risk of aggressive prostate cancer. Comparing
      high and low consumptions of well/very well cooked ground beef to no consumption
      gave OR's of 2.04 (95% CI:1.41-2.96) and 1.51 (95% CI:1.06-2.14), respectively.
      In contrast, consumption of rare/medium cooked ground beef was not associated
      with aggressive prostate cancer. Looking at meat mutagens produced by cooking at
      high temperatures, we detected an increased risk with 2-amino-3,8-Dimethylimidazo
      [4,5-f]Quinolaxine (MelQx) and 2-amino-3,4,8-trimethylimidazo(4,5-f)qunioxaline
      (DiMelQx), when comparing the highest to lowest quartiles of intake: OR = 1.69
      (95% CI:1.08-2.64;P-trend = 0.02) and OR = 1.53 (95% CI:1.00-2.35; P-trend =
      0.005), respectively. DISCUSSION: Higher intake of well-done grilled or barbequed
      red meat and ensuing carcinogens could increase the risk of aggressive prostate
      cancer.

PMID- 22132130
TI  - Evaluation of an AAV2-based rapamycin-regulated glial cell line-derived
      neurotrophic factor (GDNF) expression vector system.
AB  - Effective regulation of transgene product in anatomically circumscribed brain
      tissue is dependent on the pharmacokinetics of the regulating agent, the kinetics
      of transcriptional activation and degradation of the transgene product. We
      evaluated rapamycin-regulated AAV2-GDNF expression in the rat brain (striatum).
      Regulated (a dual-component system: AAV2-FBZhGDNF + AAV2-TF1Nc) and constitutive
      (CMV-driven) expression vectors were compared. Constitutively active AAV2-GDNF
      directed stable GDNF expression in a dose-dependent manner and it increased for
      the first month, thereafter reaching a plateau that was maintained over a further
      3 months. For the AAV2-regGDNF, rapamycin was administered in a 3-days on/4-days
      off cycle. Intraperitoneal, oral, and direct brain delivery (CED) of rapamycin
      were evaluated. Two cycles of rapamycin at an intraperitoneal dose of 10 mg/kg
      gave the highest GDNF level (2.75+/-0.01 ng/mg protein). Six cycles at 3 mg/kg
      resulted in lower GDNF values (1.36+/-0.3 ng/mg protein). Interestingly, CED of
      rapamycin into the brain at a very low dose (50 ng) induced GDNF levels
      comparable to a 6-week intraperitoneal rapamycin cycle. This study demonstrates
      the effectiveness of rapamycin regulation in the CNS. However, the kinetics of
      the transgene in brain tissue, the regulator dosing amount and schedule are
      critical parameters that influence the kinetics of accumulation and zenith of the
      encoded transgene product.

PMID- 22132131
TI  - Murine pancreatic adenocarcinoma dampens SHIP-1 expression and alters MDSC
      homeostasis and function.
AB  - BACKGROUND: Pancreatic cancer is one of the most aggressive cancers, with tumor
      induced myeloid-derived suppressor cells (MDSC) contributing to its pathogenesis
      and ineffective therapies. In response to cytokine/chemokine receptor activation,
      src homology 2 domain-containing inositol 5'-phosphatase-1 (SHIP-1) influences
      phosphatidylinositol-3-kinase (PI3K) signaling events, which regulate
      immunohomeostasis. We hypothesize that factors from murine pancreatic cancer
      cells cause the down-regulation of SHIP-1 expression, which may potentially
      contribute to MDSC expansion, and the suppression of CD8(+) T cell immune
      responses. Therefore, we sought to determine the role of SHIP-1 in solid tumor
      progression, such as murine pancreatic cancer. METHODOLOGY AND PRINCIPAL
      FINDINGS: Immunocompetent C57BL/6 mice were inoculated with either murine Panc02
      cells (tumor-bearing [TB] mice) or Phosphate Buffer Saline (PBS) (control mice).
      Cytometric Bead Array (CBA) analysis of supernatants of cultured Panc02 detected
      pro-inflammatory cytokines such as IL-6, IL-10 and MCP-1. TB mice showed a
      significant increase in serum levels of pro-inflammatory factors IL-6 and MCP-1
      measured by CBA. qRT-PCR and Western blot analyses revealed the in vivo down
      regulation of SHIP-1 expression in splenocytes from TB mice. Western blot
      analyses also detected reduced SHIP-1 activity, increased AKT-1 and BAD hyper
      phosphorylation and up-regulation of BCL-2 expression in splenocytes from TB
      mice. In vitro, qRT-PCR and Western blot analyses detected reduced SHIP-1 mRNA
      and protein expression in control splenocytes co-cultured with Panc02 cells. Flow
      cytometry results showed significant expansion of MDSC in peripheral blood and
      splenocytes from TB mice. AutoMACS sorted TB MDSC exhibited hyper-phosphorylation
      of AKT-1 and over-expression of BCL-2 detected by western blot analysis. TB MDSC
      significantly suppressed antigen-specific CD8(+) T cell immune responses in
      vitro. CONCLUSION/SIGNIFICANCE: SHIP-1 may regulate immune development that
      impacts MDSC expansion and function, contributing to pancreatic tumor
      progression. Thus, SHIP-1 can be a potential therapeutic target to help restore
      immunohomeostasis and improve therapeutic responses in patients with pancreatic
      cancer.

PMID- 22132132
TI  - RAxML and FastTree: comparing two methods for large-scale maximum likelihood
      phylogeny estimation.
AB  - Statistical methods for phylogeny estimation, especially maximum likelihood (ML),
      offer high accuracy with excellent theoretical properties. However, RAxML, the
      current leading method for large-scale ML estimation, can require weeks or longer
      when used on datasets with thousands of molecular sequences. Faster methods for
      ML estimation, among them FastTree, have also been developed, but their relative
      performance to RAxML is not yet fully understood. In this study, we explore the
      performance with respect to ML score, running time, and topological accuracy, of
      FastTree and RAxML on thousands of alignments (based on both simulated and
      biological nucleotide datasets) with up to 27,634 sequences. We find that when
      RAxML and FastTree are constrained to the same running time, FastTree produces
      topologically much more accurate trees in almost all cases. We also find that
      when RAxML is allowed to run to completion, it provides an advantage over
      FastTree in terms of the ML score, but does not produce substantially more
      accurate tree topologies. Interestingly, the relative accuracy of trees computed
      using FastTree and RAxML depends in part on the accuracy of the sequence
      alignment and dataset size, so that FastTree can be more accurate than RAxML on
      large datasets with relatively inaccurate alignments. Finally, the running times
      of RAxML and FastTree are dramatically different, so that when run to completion,
      RAxML can take several orders of magnitude longer than FastTree to complete.
      Thus, our study shows that very large phylogenies can be estimated very quickly
      using FastTree, with little (and in some cases no) degradation in tree accuracy,
      as compared to RAxML.

PMID- 22132133
TI  - Sensitivity of genome-wide-association signals to phenotyping strategy: the PROP
      TAS2R38 taste association as a benchmark.
AB  - Natural genetic variation can have a pronounced influence on human taste
      perception, which in turn may influence food preference and dietary choice.
      Genome-wide association studies represent a powerful tool to understand this
      influence. To help optimize the design of future genome-wide-association studies
      on human taste perception we have used the well-known TAS2R38-PROP association as
      a tool to determine the relative power and efficiency of different phenotyping
      and data-analysis strategies. The results show that the choice of both data
      collection and data processing schemes can have a very substantial impact on the
      power to detect genotypic variation that affects chemosensory perception. Based
      on these results we provide practical guidelines for the design of future GWAS
      studies on chemosensory phenotypes. Moreover, in addition to the TAS2R38 gene
      past studies have implicated a number of other genetic loci to affect taste
      sensitivity to PROP and the related bitter compound PTC. None of these other
      locations showed genome-wide significant associations in our study. To facilitate
      further, target-gene driven, studies on PROP taste perception we provide the
      genome-wide list of p-values for all SNPs genotyped in the current study.

PMID- 22132135
TI  - Structural identifiability of systems biology models: a critical comparison of
      methods.
AB  - Analysing the properties of a biological system through in silico experimentation
      requires a satisfactory mathematical representation of the system including
      accurate values of the model parameters. Fortunately, modern experimental
      techniques allow obtaining time-series data of appropriate quality which may then
      be used to estimate unknown parameters. However, in many cases, a subset of those
      parameters may not be uniquely estimated, independently of the experimental data
      available or the numerical techniques used for estimation. This lack of
      identifiability is related to the structure of the model, i.e. the system
      dynamics plus the observation function. Despite the interest in knowing a priori
      whether there is any chance of uniquely estimating all model unknown parameters,
      the structural identifiability analysis for general non-linear dynamic models is
      still an open question. There is no method amenable to every model, thus at some
      point we have to face the selection of one of the possibilities. This work
      presents a critical comparison of the currently available techniques. To this
      end, we perform the structural identifiability analysis of a collection of
      biological models. The results reveal that the generating series approach, in
      combination with identifiability tableaus, offers the most advantageous
      compromise among range of applicability, computational complexity and information
      provided.

PMID- 22132134
TI  - Feasibility of an alcohol intervention programme for TB patients with alcohol use
      disorder (AUD)--a qualitative study from Chennai, South India.
AB  - BACKGROUND: The negative influences of alcohol on TB management with regard to
      delays in seeking care as well as non compliance for treatment has been well
      documented. This study is part of a larger study on the prevalence of AUD
      (Alcohol Use Disorder) among TB patients which revealed that almost a quarter of
      TB patients who consumed alcohol could be classified as those who had AUD.
      However there is dearth of any effective alcohol intervention programme for TB
      patients with Alcohol Use Disorder (AUD). METHODOLOGY: This qualitative study
      using the ecological system model was done to gain insights into the perceived
      effect of alcohol use on TB treatment and perceived necessity of an intervention
      programme for TB patients with AUD. We used purposive sampling to select 44 men
      from 73 TB patients with an AUDIT score >8. Focus group discussions (FGDs) and
      interviews were conducted with TB patients with AUD, their family members and
      health providers. RESULTS: TB patients with AUD report excessive alcohol intake
      as one of the reasons for their vulnerability for TB. Peer pressure has been
      reported by many as the main reason for alcohol consumption. The influences of
      alcohol use on TB treatment has been elaborated especially with regard to the
      fears around the adverse effects of alcohol on TB drugs and the fear of being
      reprimanded by health providers. The need for alcohol intervention programs was
      expressed by the TB patients, their families and health providers. Suggestions
      for the intervention programmes included individual and group sessions,
      involvement of family members, audiovisual aids and the importance of
      sensitization by health staff. CONCLUSIONS: The findings call for urgent need
      based interventions which need to be pilot tested with a randomized control trial
      to bring out a model intervention programme for TB patients with AUD.

PMID- 22132136
TI  - The catechol-O-methyltransferase (COMT) val158met polymorphism affects brain
      responses to repeated painful stimuli.
AB  - Despite the explosion of interest in the genetic underpinnings of individual
      differences in pain sensitivity, conflicting findings have emerged for most of
      the identified "pain genes". Perhaps the prime example of this inconsistency is
      represented by catechol-O-methyltransferase (COMT), as its substantial
      association to pain sensitivity has been reported in various studies, but
      rejected in several others. In line with findings from behavioral studies, we
      hypothesized that the effect of COMT on pain processing would become apparent
      only when the pain system was adequately challenged (i.e., after repeated pain
      stimulation). In the present study, we used functional Magnetic Resonance Imaging
      (fMRI) to investigate the brain response to heat pain stimuli in 54 subjects
      genotyped for the common COMT val158met polymorphism (val/val = n 22, val/met = n
      20, met/met = n 12). Met/met subjects exhibited stronger pain-related fMRI
      signals than val/val in several brain structures, including the periaqueductal
      gray matter, lingual gyrus, cerebellum, hippocampal formation and precuneus.
      These effects were observed only for high intensity pain stimuli after repeated
      administration. In spite of our relatively small sample size, our results suggest
      that COMT appears to affect pain processing. Our data demonstrate that the effect
      of COMT on pain processing can be detected in presence of 1) a sufficiently
      robust challenge to the pain system to detect a genotype effect, and/or 2) the
      recruitment of pain-dampening compensatory mechanisms by the putatively more pain
      sensitive met homozygotes. These findings may help explain the inconsistencies in
      reported findings of the impact of COMT in pain regulation.

PMID- 22132137
TI  - Neural correlates of effective learning in experienced medical decision-makers.
AB  - Accurate associative learning is often hindered by confirmation bias and success
      chasing, which together can conspire to produce or solidify false beliefs in the
      decision-maker. We performed functional magnetic resonance imaging in 35
      experienced physicians, while they learned to choose between two treatments in a
      series of virtual patient encounters. We estimated a learning model for each
      subject based on their observed behavior and this model divided clearly into high
      performers and low performers. The high performers showed small, but equal
      learning rates for both successes (positive outcomes) and failures (no response
      to the drug). In contrast, low performers showed very large and asymmetric
      learning rates, learning significantly more from successes than failures; a
      tendency that led to sub-optimal treatment choices. Consistently with these
      behavioral findings, high performers showed larger, more sustained BOLD responses
      to failed vs. successful outcomes in the dorsolateral prefrontal cortex and
      inferior parietal lobule while low performers displayed the opposite response
      profile. Furthermore, participants' learning asymmetry correlated with
      anticipatory activation in the nucleus accumbens at trial onset, well before
      outcome presentation. Subjects with anticipatory activation in the nucleus
      accumbens showed more success-chasing during learning. These results suggest that
      high performers' brains achieve better outcomes by attending to informative
      failures during training, rather than chasing the reward value of successes. The
      differential brain activations between high and low performers could potentially
      be developed into biomarkers to identify efficient learners on novel decision
      tasks, in medical or other contexts.

PMID- 22132138
TI  - Feasibility of bispectral index-guided propofol infusion for flexible
      bronchoscopy sedation: a randomized controlled trial.
AB  - OBJECTIVES: There are safety issues associated with propofol use for flexible
      bronchoscopy (FB). The bispectral index (BIS) correlates well with the level of
      consciousness. The aim of this study was to show that BIS-guided propofol
      infusion is safe and may provide better sedation, benefiting the patients and
      bronchoscopists. METHODS: After administering alfentanil bolus, 500 patients were
      randomized to either propofol infusion titrated to a BIS level of 65-75 (study
      group) or incremental midazolam bolus based on clinical judgment to achieve
      moderate sedation. The primary endpoint was safety, while the secondary endpoints
      were recovery time, patient tolerance, and cooperation. RESULTS: The proportion
      of patients with hypoxemia or hypotensive events were not different in the 2
      groups (study vs. control groups: 39.9% vs. 35.7%, p = 0.340; 7.4% vs. 4.4%, p =
      0.159, respectively). The mean lowest blood pressure was lower in the study
      group. Logistic regression revealed male gender, higher American Society of
      Anesthesiologists physical status, and electrocautery were associated with
      hypoxemia, whereas lower propofol dose for induction was associated with
      hypotension in the study group. The study group had better global tolerance
      (p<0.001), less procedural interference by movement or cough (13.6% vs. 36.1%,
      p<0.001; 30.0% vs. 44.2%, p = 0.001, respectively), and shorter time to
      orientation and ambulation (11.7+/-10.2 min vs. 29.7+/-26.8 min, p<0.001; 30.0+/
      18.2 min vs. 55.7+/-40.6 min, p<0.001, respectively) compared to the control
      group. CONCLUSIONS: BIS-guided propofol infusion combined with alfentanil for FB
      sedation provides excellent patient tolerance, with fast recovery and less
      procedure interference. TRIAL REGISTRATION: ClinicalTrials. gov NCT00789815.

PMID- 22132139
TI  - Global mapping of H3K4me1 and H3K4me3 reveals the chromatin state-based cell type
      specific gene regulation in human Treg cells.
AB  - Regulatory T cells (Treg) contribute to the crucial immunological processes of
      self-tolerance and immune homeostasis. Genomic mechanisms that regulate cell fate
      decisions leading to Treg or conventional T cells (Tconv) lineages and those
      underlying Treg function remain to be fully elucidated, especially at the histone
      modification level. We generated high-resolution genome-wide distribution maps of
      monomethylated histone H3 lysine 4 (H3K4me1) and trimethylated H3K4 (H3K4me3) in
      human CD4(+)CD25(+)FOXP3(+) Tregs and CD4(+)CD25(+)FOXP3(-) activated (a)Tconv
      cells by DNA sequencing-by-synthesis. 2115 H3K4me3 regions corresponded to
      proximal promoters; in Tregs, the genes associated with these regions included
      the master regulator FOXP3 and the chemokine (C-C motif) receptor 7 (CCR7). 41024
      Treg-specific H3K4me1 regions were identified. The majority of the H3K4me1
      regions differing between Treg and aTconv cells were located at promoter-distal
      sites, and in vitro reporter gene assays were used to evaluate and identify novel
      enhancer activity. We provide for the first time a comprehensive genome-wide
      dataset of lineage-specific H3K4me1 and H3K4me3 patterns in Treg and aTconv
      cells, which may control cell type-specific gene regulation. This basic principle
      is likely not restricted to the two closely-related T cell populations, but may
      apply generally to somatic cell lineages in adult organisms.

PMID- 22132140
TI  - Beyond the colours: discovering hidden diversity in the Nymphalidae of the
      Yucatan Peninsula in Mexico through DNA barcoding.
AB  - BACKGROUND: Recent studies have demonstrated the utility of DNA barcoding in the
      discovery of overlooked species and in the connection of immature and adult
      stages. In this study, we use DNA barcoding to examine diversity patterns in 121
      species of Nymphalidae from the Yucatan Peninsula in Mexico. Our results suggest
      the presence of cryptic species in 8 of these 121 taxa. As well, the reference
      database derived from the analysis of adult specimens allowed the identification
      of nymphalid caterpillars providing new details on host plant use.
      METHODOLOGY/PRINCIPAL FINDINGS: We gathered DNA barcode sequences from 857 adult
      Nymphalidae representing 121 different species. This total includes four species
      (Adelpha iphiclus, Adelpha malea, Hamadryas iphtime and Taygetis laches) that
      were initially overlooked because of their close morphological similarity to
      other species. The barcode results showed that each of the 121 species possessed
      a diagnostic array of barcode sequences. In addition, there was evidence of
      cryptic taxa; seven species included two barcode clusters showing more than 2%
      sequence divergence while one species included three clusters. All 71 nymphalid
      caterpillars were identified to a species level by their sequence congruence to
      adult sequences. These caterpillars represented 16 species, and included
      Hamadryas julitta, an endemic species from the Yucatan Peninsula whose larval
      stages and host plant (Dalechampia schottii, also endemic to the Yucatan
      Peninsula) were previously unknown. CONCLUSIONS/SIGNIFICANCE: This investigation
      has revealed overlooked species in a well-studied museum collection of nymphalid
      butterflies and suggests that there is a substantial incidence of cryptic species
      that await full characterization. The utility of barcoding in the rapid
      identification of caterpillars also promises to accelerate the assembly of
      information on life histories, a particularly important advance for hyperdiverse
      tropical insect assemblages.

PMID- 22132141
TI  - Longitudinal study on methicillin-resistant Staphylococcus pseudintermedius in
      households.
AB  - Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an emerging
      pathogen in dogs and has been found in Europe, Asia and North America. To date
      most studies are one-point prevalence studies and therefore little is known about
      the dynamics of MRSP in dogs and their surrounding. In this longitudinal study
      MRSP colonization in dogs and the transmission of MRSP to humans, contact animals
      and the environment was investigated. Sixteen dogs with a recent clinical MRSP
      infection were included. The index dogs, contact animals, owners and environments
      were sampled once a month for six months. Samples taken from the nose, perineum
      and infection site (if present) of the index cases and contact animals, and the
      nares of the owners were cultured using pre-enrichment. Index cases were found
      positive for prolonged periods of time, in two cases during all six samplings. In
      five of the 12 households that were sampled during six months, the index case was
      intermittently found MRSP-positive. Contact animals and the environment were also
      found MRSP-positive, most often in combination with a MRSP-positive index dog. In
      four households positive environmental samples were found while no animals or
      humans were MRSP-positive, indicating survival of MRSP in the environment for
      prolonged periods of time. Genotyping revealed that generally similar or
      indistinguishable MRSP isolates were found in patients, contact animals and
      environmental samples within the same household. Within two households, however,
      genetically distinct MRSP isolates were found. These results show that
      veterinarians should stay alert with (former) MRSP patients, even after repeated
      MRSP-negative cultures or after the disappearance of the clinical infection.
      There is a considerable risk of transmission of MRSP to animals in close contact
      with MRSP patients. Humans were rarely MRSP-positive and never tested MRSP
      positive more than once suggesting occasional contamination or rapid elimination
      of colonization of the owners.

PMID- 22132143
TI  - Fine-scale analysis reveals cryptic landscape genetic structure in desert
      tortoises.
AB  - Characterizing the effects of landscape features on genetic variation is
      essential for understanding how landscapes shape patterns of gene flow and
      spatial genetic structure of populations. Most landscape genetics studies have
      focused on patterns of gene flow at a regional scale. However, the genetic
      structure of populations at a local scale may be influenced by a unique suite of
      landscape variables that have little bearing on connectivity patterns observed at
      broader spatial scales. We investigated fine-scale spatial patterns of genetic
      variation and gene flow in relation to features of the landscape in desert
      tortoise (Gopherus agassizii), using 859 tortoises genotyped at 16 microsatellite
      loci with associated data on geographic location, sex, elevation, slope, and soil
      type, and spatial relationship to putative barriers (power lines, roads). We used
      spatially explicit and non-explicit Bayesian clustering algorithms to partition
      the sample into discrete clusters, and characterize the relationships between
      genetic distance and ecological variables to identify factors with the greatest
      influence on gene flow at a local scale. Desert tortoises exhibit weak genetic
      structure at a local scale, and we identified two subpopulations across the study
      area. Although genetic differentiation between the subpopulations was low, our
      landscape genetic analysis identified both natural (slope) and anthropogenic
      (roads) landscape variables that have significantly influenced gene flow within
      this local population. We show that desert tortoise movements at a local scale
      are influenced by features of the landscape, and that these features are
      different than those that influence gene flow at larger scales. Our findings are
      important for desert tortoise conservation and management, particularly in light
      of recent translocation efforts in the region. More generally, our results
      indicate that recent landscape changes can affect gene flow at a local scale and
      that their effects can be detected almost immediately.

PMID- 22132142
TI  - Glucocorticoid regulation of SLIT/ROBO tumour suppressor genes in the ovarian
      surface epithelium and ovarian cancer cells.
AB  - The three SLIT ligands and their four ROBO receptors have fundamental roles in
      mammalian development by promoting apoptosis and repulsing aberrant cell
      migration. SLITs and ROBOs have emerged as candidate tumour suppressor genes
      whose expression is inhibited in a variety of epithelial tumours. We demonstrated
      that their expression could be negatively regulated by cortisol in normal ovarian
      luteal cells. We hypothesised that after ovulation the locally produced cortisol
      would inhibit SLIT/ROBO expression in the ovarian surface epithelium (OSE) to
      facilitate its repair and that this regulatory pathway was still present, and
      could be manipulated, in ovarian epithelial cancer cells. Here we examined the
      expression and regulation of the SLIT/ROBO pathway in OSE, ovarian cancer
      epithelial cells and ovarian tumour cell lines. Basal SLIT2, SLIT3, ROBO1, ROBO2
      and ROBO4 expression was lower in primary cultures of ovarian cancer epithelial
      cells when compared to normal OSE (P<0.05) and in poorly differentiated SKOV-3
      cells compared to the more differentiated PEO-14 cells (P<0.05). Cortisol reduced
      the expression of certain SLITs and ROBOs in normal OSE and PEO-14 cells
      (P<0.05). Furthermore blocking SLIT/ROBO activity reduced apoptosis in both PEO
      14 and SKOV-3 tumour cells (P<0.05). Interestingly SLIT/ROBO expression could be
      increased by reducing the expression of the glucocorticoid receptor using siRNA
      (P<0.05). Overall our findings indicate that in the post-ovulatory phase one role
      of cortisol may be to temporarily inhibit SLIT/ROBO expression to facilitate
      regeneration of the OSE. Therefore this pathway may be a target to develop
      strategies to manipulate the SLIT/ROBO system in ovarian cancer.

PMID- 22132144
TI  - The phenotype-fitness map in experimental evolution of phages.
AB  - Evolutionary biologists commonly interpret adaptations of organisms by reference
      to a phenotype-fitness map, a model of how different states of a phenotype affect
      fitness. Notwithstanding the popularity of this approach, it remains difficult to
      directly test these mappings, both because the map often describes only a small
      subset of phenotypes contributing to total fitness and because direct measures of
      fitness are difficult to obtain and compare to the map. Both limitations can be
      overcome for bacterial viruses (phages) grown in the experimental condition of
      unlimited hosts. A complete accounting of fitness requires 3 easily measured
      phenotypes, and total fitness is also directly measurable for arbitrary
      genotypes. Yet despite the presumed transparency of this system, directly
      estimated fitnesses often differ from fitnesses calculated from the phenotype
      fitness map. This study attempts to resolve these discrepancies, both by
      developing a more exact analytical phenotype-fitness map and by exploring the
      empirical foundations of direct fitness estimates. We derive an equation (the
      phenotype-fitness map) for exponential phage growth that allows an arbitrary
      distribution of lysis times and burst sizes. We also show that direct estimates
      of fitness are, in many cases, plausibly in error because the population has not
      attained stable age distribution and thus violates the model underlying the
      phenotype-fitness map. In conjunction with data provided here, the new
      understanding appears to resolve a discrepancy between the reported fitness of
      phage T7 and the substantially lower value calculated from its phenotype-fitness
      map.

PMID- 22132145
TI  - Generation of immortal cell lines from the adult pituitary: role of cAMP on
      differentiation of SOX2-expressing progenitor cells to mature gonadotropes.
AB  - The pituitary is a complex endocrine tissue composed of a number of unique cell
      types distinguished by the expression and secretion of specific hormones, which
      in turn control critical components of overall physiology. The basic function of
      these cells is understood; however, the molecular events involved in their
      hormonal regulation are not yet fully defined. While previously established cell
      lines have provided much insight into these regulatory mechanisms, the
      availability of representative cell lines from each cell lineage is limited, and
      currently none are derived from adult pituitary. We have therefore used
      retroviral transfer of SV40 T-antigen to mass immortalize primary pituitary cell
      culture from an adult mouse. We have generated 19 mixed cell cultures that
      contain cells from pituitary cell lineages, as determined by RT-PCR analysis and
      immunocytochemistry for specific hormones. Some lines expressed markers
      associated with multipotent adult progenitor cells or transit-amplifying cells,
      including SOX2, nestin, S100, and SOX9. The progenitor lines were exposed to an
      adenylate cyclase activator, forskolin, over 7 days and were induced to
      differentiate to a more mature gonadotrope cell, expressing significant levels of
      alpha-subunit, LHbeta, and FSHbeta mRNAs. Additionally, clonal populations of
      differentiated gonadotropes were exposed to 30 nM gonadotropin-releasing hormone
      and responded appropriately with a significant increase in alpha-subunit and
      LHbeta transcription. Further, exposure of the lines to a pulse paradigm of GnRH,
      in combination with 17beta-estradiol and dexamethasone, significantly increased
      GnRH receptor mRNA levels. This array of adult-derived pituitary cell models will
      be valuable for both studies of progenitor cell characteristics and modulation,
      and the molecular analysis of individual pituitary cell lineages.

PMID- 22132147
TI  - BMI-1 autoantibody as a new potential biomarker for cervical carcinoma.
AB  - BMI-1 is overexpressed in a variety of cancers, which can elicit an immune
      response leading to the induction of autoantibodies. However, BMI-1 autoantibody
      as a biomarker has seldom been studied with the exception of nasopharyngeal
      carcinoma. Whether BMI-1 autoantibodies can be used as a biomarker for cervical
      carcinoma is unclear. In this study,BMI-1 proteins were isolated by screening of
      a T7 phage cDNA library from mixed cervical carcinoma tissues. We analyzed BMI-1
      autoantibody levels in serum samples from 67 patients with cervical carcinoma and
      65 controls using ELISA and immunoblot. BMI-1 mRNA or protein levels were over
      expressed in cervical carcinoma cell lines. Immunoblot results exhibited
      increased BMI-1 autoantibody levels in patient sera compared to normal sera.
      Additionally, the results for antibody affinity assay showed that there was no
      difference between cervical polyps and normal sera of BMI-1 autoantibody levels,
      but it was significantly greater in patient sera than that in normal controls
      (patient 0.827+/-0.043 and normal 0.445+/-0.023; P<0.001). What's more, the
      levels of BMI-1 autoantibody increased significantly at stage I (0.672+/-0.019)
      compared to normal sera (P<0.001), and levels of BMI-1 autoantibodies were
      increased gradually during the tumor progression (stage I 0.672+/-0.019; stage II
      0.775 +/-0.019; stage III 0.890 +/-0.027; stage IV 1.043+/-0.041), which were
      significantly correlated with disease progression of cervical cancer (P<0.001).
      Statistical analyses using logistic regression and receiver operating
      characteristics (ROC) curves indicated that the BMI-1 autoantibody level can be
      used as a biomarker for cervical carcinoma (sensitivity 0.78 and specificity
      0.76; AUC = 0.922). In conclusion, measuring BMI-1 autoantibody levels of
      patients with cervical cancer could have clinical prognostic value as well as a
      non-tissue specific biomarker for neoplasms expressing BMI-1.

PMID- 22132146
TI  - Molecular epidemiology of influenza A/H3N2 viruses circulating in Uganda.
AB  - The increasing availability of complete influenza virus genomes is deepening our
      understanding of influenza evolutionary dynamics and facilitating the selection
      of vaccine strains. However, only one complete African influenza virus sequence
      is available in the public domain. Here we present a complete genome analysis of
      59 influenza A/H3N2 viruses isolated from humans in Uganda during the 2008 and
      2009 season. Isolates were recovered from hospital-based sentinel surveillance
      for influenza-like illnesses and their whole genome sequenced. The viruses
      circulating during these two seasons clearly differed from each other
      phylogenetically. They showed a slow evolution away from the 2009/10 recommended
      vaccine strain (A/Brisbane/10/07), instead clustering with the 2010/11
      recommended vaccine strain (A/Perth/16/09) in the A/Victoria/208/09 clade, as
      observed in other global regions. All of the isolates carried the adamantane
      resistance marker S31N in the M2 gene and carried several markers of enhanced
      transmission; as expected, none carried any marker of neuraminidase inhibitor
      resistance. The hemagglutinin gene of the 2009 isolates differed from that of the
      2008 isolates in antigenic sites A, B, D, and to a lesser extent, C and E
      indicating evidence of an early phylogenetic shift from the 2008 to 2009 viruses.
      The internal genes of the 2009 isolates were similar to those of one 2008
      isolate, A/Uganda/MUWRP-050/2008. Another 2008 isolate had a truncated PB1-F2
      protein. Whole genome sequencing can enhance surveillance of future seasonal
      changes in the viral genome which is crucial to ensure that selected vaccine
      strains are protective against the strains circulating in Eastern Africa. This
      data provides an important baseline for this surveillance. Overall the influenza
      virus activity in Uganda appears to mirror that observed in other regions of the
      southern hemisphere.

PMID- 22132148
TI  - The putative endoglucanase PcGH61D from Phanerochaete chrysosporium is a metal
      dependent oxidative enzyme that cleaves cellulose.
AB  - Many fungi growing on plant biomass produce proteins currently classified as
      glycoside hydrolase family 61 (GH61), some of which are known to act
      synergistically with cellulases. In this study we show that PcGH61D, the gene
      product of an open reading frame in the genome of Phanerochaete chrysosporium, is
      an enzyme that cleaves cellulose using a metal-dependent oxidative mechanism that
      leads to generation of aldonic acids. The activity of this enzyme and its
      beneficial effect on the efficiency of classical cellulases are stimulated by the
      presence of electron donors. Experiments with reduced cellulose confirmed the
      oxidative nature of the reaction catalyzed by PcGH61D and indicated that the
      enzyme may be capable of penetrating into the substrate. Considering the
      abundance of GH61-encoding genes in fungi and genes encoding their functional
      bacterial homologues currently classified as carbohydrate binding modules family
      33 (CBM33), this enzyme activity is likely to turn out as a major determinant of
      microbial biomass-degrading efficiency.

PMID- 22132149
TI  - Molecular evolution of the transmembrane domains of G protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) are a superfamily of integral membrane
      proteins vital for signaling and are important targets for pharmaceutical
      intervention in humans. Previously, we identified a group of ten amino acid
      positions (called key positions), within the seven transmembrane domain (7TM)
      interhelical region, which had high mutual information with each other and many
      other positions in the 7TM. Here, we estimated the evolutionary selection
      pressure at those key positions. We found that the key positions of receptors for
      small molecule natural ligands were under strong negative selection. Receptors
      naturally activated by lipids had weaker negative selection in general when
      compared to small molecule-activated receptors. Selection pressure varied widely
      in peptide-activated receptors. We used this observation to predict that a
      subgroup of orphan GPCRs not under strong selection may not possess a natural
      small-molecule ligand. In the subgroup of MRGX1-type GPCRs, we identified a key
      position, along with two non-key positions, under statistically significant
      positive selection.

PMID- 22132150
TI  - Highly pathogenic avian influenza virus H5N1 infection in a long-distance migrant
      shorebird under migratory and non-migratory states.
AB  - Corticosterone regulates physiological changes preparing wild birds for
      migration. It also modulates the immune system and may lead to increased
      susceptibility to infection, with implications for the spread of pathogens,
      including highly pathogenic avian influenza virus (HPAIV) H5N1. The red knot
      (Calidris canutus islandica) displays migratory changes in captivity and was used
      as a model to assess the effect of high plasma concentration of corticosterone on
      HPAIV H5N1 infection. We inoculated knots during pre-migration (N = 6), fueling
      (N = 5), migration (N = 9) and post-migration periods (N = 6). Knots from all
      groups shed similar viral titers for up to 5 days post-inoculation (dpi), peaking
      at 1 to 3 dpi. Lesions of acute encephalitis, associated with virus replication
      in neurons, were seen in 1 to 2 knots per group, leading to neurological disease
      and death at 5 to 11 dpi. Therefore, the risk of HPAIV H5N1 infection in wild
      birds and of potential transmission between wild birds and poultry may be similar
      at different times of the year, irrespective of wild birds' migratory status.
      However, in knots inoculated during the migration period, viral shedding levels
      positively correlated with pre-inoculation plasma concentration of
      corticosterone. Of these, knots that did not become productively infected had
      lower plasma concentration of corticosterone. Conversely, elevated plasma
      concentration of corticosterone did not result in an increased probability to
      develop clinical disease. These results suggest that birds with elevated plasma
      concentration of corticosterone at the time of migration (ready to migrate) may
      be more susceptible to acquisition of infection and shed higher viral titers-
      before the onset of clinical disease--than birds with low concentration of
      corticosterone (not ready for take-off). Yet, they may not be more prone to the
      development of clinical disease. Therefore, assuming no effect of sub-clinical
      infection on the likelihood of migratory take-off, this may favor the spread of
      HPAIV H5N1 by migratory birds over long distances.

PMID- 22132151
TI  - MicroRNA alterations and associated aberrant DNA methylation patterns across
      multiple sample types in oral squamous cell carcinoma.
AB  - BACKGROUND: MicroRNA (miRNA) expression is broadly altered in cancer, but few
      studies have investigated miRNA deregulation in oral squamous cell carcinoma
      (OSCC). Epigenetic mechanisms are involved in the regulation of >30 miRNA genes
      in a range of tissues, and we aimed to investigate this further in OSCC. METHODS:
      TaqMan(r) qRT-PCR arrays and individual assays were used to profile miRNA
      expression in a panel of 25 tumors with matched adjacent tissues from patients
      with OSCC, and 8 control paired oral stroma and epithelium from healthy
      volunteers. Associated DNA methylation changes of candidate epigenetically
      deregulated miRNA genes were measured in the same samples using the MassArray(r)
      mass spectrometry platform. MiRNA expression and DNA methylation changes were
      also investigated in FACS sorted CD44(high) oral cancer stem cells from primary
      tumor samples (CSCs), and in oral rinse and saliva from 15 OSCC patients and 7
      healthy volunteers. RESULTS: MiRNA expression patterns were consistent in healthy
      oral epithelium and stroma, but broadly altered in both tumor and adjacent tissue
      from OSCC patients. MiR-375 is repressed and miR-127 activated in OSCC, and we
      confirm previous reports of miR-137 hypermethylation in oral cancer. The miR-200
      s/miR-205 were epigenetically activated in tumors vs normal tissues, but
      repressed in the absence of DNA hypermethylation specifically in CD44(high) oral
      CSCs. Aberrant miR-375 and miR-200a expression and miR-200c-141 methylation could
      be detected in and distinguish OSCC patient oral rinse and saliva from healthy
      volunteers, suggesting a potential clinical application for OSCC specific miRNA
      signatures in oral fluids. CONCLUSIONS: MiRNA expression and DNA methylation
      changes are a common event in OSCC, and we suggest miR-375, miR-127, miR-137, the
      miR-200 family and miR-205 as promising candidates for future investigations.
      Although overall activated in OSCC, miR-200/miR-205 suppression in oral CSCs
      indicate that cell specific silencing of these miRNAs may drive tumor expansion
      and progression.

PMID- 22132152
TI  - P(5A)-type ATPase Cta4p is essential for Ca2+ transport in the endoplasmic
      reticulum of Schizosaccharomyces pombe.
AB  - This study establishes the role of P(5A)-type Cta4 ATPase in Ca(2+) sequestration
      in the endoplasmic reticulum by detecting an ATP-dependent, vanadate-sensitive
      and FCCP insensitive (45)Ca(2+)-transport in fission yeast membranes isolated by
      cellular fractionation. Specifically, the Ca(2+)-ATPase transport activity was
      decreased in ER membranes isolated from cells lacking a cta4(+) gene.
      Furthermore, a disruption of cta4(+) resulted in 6-fold increase of intracellular
      Ca(2+) levels, sensitivity towards accumulation of misfolded proteins in ER and
      ER stress, stimulation of the calcineurin phosphatase activity and vacuolar
      Ca(2+) pumping. These data provide compelling biochemical evidence for a P(5A)
      type Cta4 ATPase as an essential component of Ca(2+) transport system and
      signaling network which regulate, in conjunction with calcineurin, the ER
      functionality in fission yeast.

PMID- 22132153
TI  - Cadmium-induced oxidative stress and apoptotic changes in the testis of
      freshwater crab, Sinopotamon henanense.
AB  - Cadmium (Cd), one of the most toxic environmental and industrial pollutants, is
      known to exert gonadotoxic and spermiotoxic effects. In the present study, we
      examined the toxic effect of Cd on the testis of freshwater crab, Sinopotamon
      henanense. Crabs were exposed to different Cd concentrations (from 0 to 116.00
      mg.L(-1)) for 7 d. Oxidative stress and apoptotic changes in the testes were
      detected. The activities of SOD, GPx and CAT initially increased and subsequently
      decreased with increasing Cd concentrations, which was accompanied with the
      increase in malondialdehyde (MDA) and H(2)O(2) content in a concentration
      dependent manner. Typical morphological characteristic and physiological changes
      of apoptosis were observed using a variety of methods (HE staining, AO/EB double
      fluorescent staining, Transmission Electron Microscope observation and DNA
      fragmentation analysis), and the activities of caspase-3 and caspase-9 were
      increased in a concentration-dependent manner after Cd exposure. These results
      led to the conclusion that Cd could induced oxidative damage as well as apoptosis
      in the testis, and the apoptotic processes may be mediated via mitochondria
      dependent apoptosis pathway by regulating the activities of caspase-3 and caspase
      9.

PMID- 22132154
TI  - hnRNP A1 and hnRNP F modulate the alternative splicing of exon 11 of the insulin
      receptor gene.
AB  - Exon 11 of the insulin receptor gene (INSR) is alternatively spliced in a
      developmentally and tissue-specific manner. Linker scanning mutations in a 5' GA
      rich enhancer in intron 10 identified AGGGA sequences that are important for
      enhancer function. Using RNA-affinity purification and mass spectrometry, we
      identified hnRNP F and hnRNP A1 binding to these AGGGA sites and also to similar
      motifs at the 3' end of the intron. The hnRNPs have opposite functional effects
      with hnRNP F promoting and hnRNP A1 inhibiting exon 11 inclusion, and deletion of
      the GA-rich elements eliminates both effects. We also observed specific binding
      of hnRNP A1 to the 5' splice site of intron 11. The SR protein SRSF1 (SF2/ASF) co
      purified on the GA-rich enhancer and, interestingly, also competes with hnRNP A1
      for binding to the splice site. A point mutation -3U->C decreases hnRNP A1
      binding, increases SRSF1 binding and renders the exon constitutive. Lastly, our
      data point to a functional interaction between hnRNP F and SRSF1 as a mutant that
      eliminates SRSF1 binding to exon 11, or a SRSF1 knockdown, which prevents the
      stimulatory effect of hnRNP F over expression.

PMID- 22132155
TI  - Quantitative characterization of the filiform mechanosensory hair array on the
      cricket cercus.
AB  - BACKGROUND: Crickets and other orthopteran insects sense air currents with a pair
      of abdominal appendages resembling antennae, called cerci. Each cercus in the
      common house cricket Acheta domesticus is approximately 1 cm long, and is covered
      with 500 to 750 filiform mechanosensory hairs. The distribution of the hairs on
      the cerci, as well as the global patterns of their movement vectors, have been
      characterized semi-quantitatively in studies over the last 40 years, and have
      been shown to be very stereotypical across different animals in this species.
      Although the cercal sensory system has been the focus of many studies in the
      areas of neuroethology, development, biomechanics, sensory function and neural
      coding, there has not yet been a quantitative study of the functional morphology
      of the receptor array of this important model system. METHODOLOGY/PRINCIPAL
      FINDINGS: We present a quantitative characterization of the structural
      characteristics and functional morphology of the cercal filiform hair array. We
      demonstrate that the excitatory direction along each hair's movement plane can be
      identified by features of its socket that are visible at the light-microscopic
      level, and that the length of the hair associated with each socket can also be
      estimated accurately from a structural parameter of the socket. We characterize
      the length and directionality of all hairs on the basal half of a sample of three
      cerci, and present statistical analyses of the distributions.
      CONCLUSIONS/SIGNIFICANCE: The inter-animal variation of several global
      organizational features is low, consistent with constraints imposed by functional
      effectiveness and/or developmental processes. Contrary to previous reports,
      however, we show that the filiform hairs are not re-identifiable in the strict
      sense.

PMID- 22132156
TI  - The making of a productivity hotspot in the coastal ocean.
AB  - BACKGROUND: Highly productive hotspots in the ocean often occur where complex
      physical forcing mechanisms lead to aggregation of primary and secondary
      producers. Understanding how hotspots persist, however, requires combining
      knowledge of the spatio-temporal linkages between geomorphology, physical
      forcing, and biological responses with the physiological requirements and
      movement of top predators. METHODOLOGY/PRINCIPAL FINDINGS: Here we integrate
      remotely sensed oceanography, ship surveys, and satellite telemetry to show how
      local geomorphology interacts with physical forcing to create a region with
      locally enhanced upwelling and an adjacent upwelling shadow that promotes
      retentive circulation, enhanced year-round primary production, and prey
      aggregation. These conditions provide an area within the upwelling shadow where
      physiologically optimal water temperatures can be found adjacent to a region of
      enhanced prey availability, resulting in a foraging hotspot for loggerhead sea
      turtles (Caretta caretta) off the Baja California peninsula, Mexico.
      SIGNIFICANCE/CONCLUSIONS: We have identified the set of conditions that lead to a
      persistent top predator hotspot, which increases our understanding of how highly
      migratory species exploit productive regions of the ocean. These results will aid
      in the development of spatially and environmentally explicit management
      strategies for marine species of conservation concern.

PMID- 22132157
TI  - The role of kinin receptors in preventing neuroinflammation and its clinical
      severity during experimental autoimmune encephalomyelitis in mice.
AB  - BACKGROUND: Multiple sclerosis (MS) is a demyelinating and neuroinflammatory
      disease of the human central nervous system (CNS). The expression of kinins is
      increased in MS patients, but the underlying mechanisms by which the kinin
      receptor regulates MS development have not been elucidated. METHODOLOGY/PRINCIPAL
      FINDINGS: Experimental autoimmune encephalomyelitis (EAE) was induced in female
      C57BL/6 mice by immunization with MOG(35-55) peptide emulsified in complete
      Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Here, we
      report that blockade of the B(1)R in the induction phase of EAE markedly
      suppressed its progression by interfering with the onset of the immune response.
      Furthermore, B(1)R antagonist suppressed the production/expression of antigen
      specific T(H)1 and T(H)17 cytokines and transcription factors, both in the
      periphery and in the CNS. In the chronic phase of EAE, the blockade of B(1)R
      consistently impaired the clinical progression of EAE. Conversely, administration
      of the B(1)R agonist in the acute phase of EAE suppressed disease progression and
      inhibited the increase in permeability of the blood-brain barrier (BBB) and any
      further CNS inflammation. Of note, blockade of the B(2)R only showed a moderate
      impact on all of the studied parameters of EAE progression.
      CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that kinin receptors,
      mainly the B(1)R subtype, play a dual role in EAE progression depending on the
      phase of treatment through the lymphocytes and glial cell-dependent pathways.

PMID- 22132158
TI  - miR-135A regulates preimplantation embryo development through down-regulation of
      E3 Ubiquitin Ligase Seven In Absentia Homolog 1A (SIAH1A) expression.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules capable of
      regulating transcription and translation. Previously, a cluster of miRNAs that
      are specifically expressed in mouse zygotes but not in oocytes or other
      preimplantation stages embryos are identified by multiplex real-time polymerase
      chain reaction-based miRNA profiling. The functional role of one of these zygote
      specific miRNAs, miR-135a, in preimplantation embryo development was
      investigated. METHODOLOGY/PRINCIPAL FINDINGS: Microinjection of miR-135a
      inhibitor suppressed first cell cleavage in more than 30% of the zygotes.
      Bioinformatics analysis identified E3 Ubiquitin Ligase Seven In Absentia Homolog
      1A (Siah1a) as a predicted target of miR-135a. Western blotting and 3'UTR
      luciferase functional assays demonstrated that miR-135a down-regulated the
      expression of Siah1 in HeLa cells and in mouse zygotes. Siah1a was expressed in
      preimplantation embryos and its expression pattern negatively correlated with
      that of miR-135a. Co-injection of Siah1a-specific antibody with miR-135a
      inhibitor partially nullified the effect of miR-135a inhibition. Proteasome
      inhibition by MG-132 revealed that miR-135a regulated proteasomal degradation and
      potentially controlled the expression of chemokinesin DNA binding protein (Kid).
      CONCLUSIONS/SIGNIFICANCE: The present study demonstrated for the first time that
      zygotic specific miRNA modulates the first cell cleavage through regulating
      expression of Siah1a.

PMID- 22132159
TI  - Astrocyte proliferation following stroke in the mouse depends on distance from
      the infarct.
AB  - Reactive gliosis is a hallmark of brain pathology and the injury response, yet
      the extent to which astrocytes proliferate, and whether this is central to
      astrogliosis is still controversial. We determined the fraction of mature
      astrocytes that proliferate in a mouse stroke model using unbiased stereology as
      a function of distance from the infarct edge. Cumulatively 11.1+/-1.2% of
      Aldh1l1(+) astrocytes within 400 um in the cortical penumbra incorporate BrdU in
      the first week following stroke, while the overall number of astrocytes does not
      change. The number of astrocytes proliferating fell sharply with distance with
      more than half of all proliferating astrocytes found within 100 um of the edge of
      the infarct. Despite extensive cell proliferation primarily of microglia and
      neutrophils/monocytes in the week following stroke, few mature astrocytes re
      enter cell cycle, and these are concentrated close to the infarct boundary.

PMID- 22132160
TI  - Oxidation of DJ-1 induced by 6-hydroxydopamine decreasing intracellular
      glutathione.
AB  - DJ-1, the causative gene of a familial form of Parkinson's disease (PD), has been
      reported to undergo preferential oxidation of the cysteine residue at position
      106 (Cys-106) under oxidative stress; however, details of the molecular
      mechanisms are not well known. In the present study, mechanisms of DJ-1 oxidation
      induced by 6-hydroxydopamine (6-OHDA) were investigated by using SH-SY5Y cells.
      The treatment of these cells with 6-OHDA caused an obvious acidic spot sift of DJ
      1 due to its oxidation. However, when catalase, which is an hydrogen peroxide
      (H(2)O(2))-removing enzyme, was added during the treatment, it failed to prevent
      the oxidation induced by 6-OHDA, suggesting that electrophilic p-quinone formed
      from 6-OHDA, but not H(2)O(2), was responsible for the DJ-1 oxidation.
      Benzoquinone, another electrophilic p-quinone, also induced DJ-1 oxidation. The
      intracellular glutathione (GSH) levels were significantly decreased by 6-OHDA,
      irrespective of the presence or absence of catalase. The inhibition of GSH
      synthesis by buthionine sulfoximine resulted in a decrease in GSH levels and
      enhancement of DJ-1 oxidation. The pretreatment of cells with N-acetyl-cysteine
      prevented the loss of intracellular GSH and subsequently DJ-1 oxidation induced
      by 6-OHDA. Collectively, these results suggest that electrophilic p-quinone
      formed from 6-OHDA induces DJ-1 oxidation by decreasing intracellular GSH.

PMID- 22132161
TI  - Implantation serine proteinase 1 exhibits mixed substrate specificity that
      silences signaling via proteinase-activated receptors.
AB  - Implantation S1 family serine proteinases (ISPs) are tryptases involved in embryo
      hatching and uterine implantation in the mouse. The two different ISP proteins
      (ISP1 and ISP2) have been detected in both pre- and post-implantation embryo
      tissue. To date, native ISP obtained from uterus and blastocyst tissues has been
      isolated only as an active hetero-dimer that exhibits trypsin-like substrate
      specificity. We hypothesised that in isolation, ISP1 might have a unique
      substrate specificity that could relate to its role when expressed alone in
      individual tissues. Thus, we isolated recombinant ISP1 expressed in Pichia
      pastoris and evaluated its substrate specificity. Using several chromogenic
      substrates and serine proteinase inhibitors, we demonstrate that ISP1 exhibits
      trypsin-like substrate specificity, having a preference for lysine over arginine
      at the P1 position. Phage display peptide mimetics revealed an expanded but mixed
      substrate specificity of ISP1, including chymotryptic and elastase activity.
      Based upon targets observed using phage display, we hypothesised that ISP1 might
      signal to cells by cleaving and activating proteinase-activated receptors (PARs)
      and therefore assessed PARs 1, 2 and 4 as potential ISP1 targets. We observed
      that ISP1 silenced enzyme-triggered PAR signaling by receptor-disarming. This PAR
      disarming action of ISP1 may be important for embryo development and
      implantation.

PMID- 22132162
TI  - DNA methylation profiles of primary colorectal carcinoma and matched liver
      metastasis.
AB  - BACKGROUND: The contribution of DNA methylation to the metastatic process in
      colorectal cancers (CRCs) is unclear. METHODS: We evaluated the methylation
      status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13,
      THBS1, MGMT, HPP1 and ERalpha) by bisulfite-pyrosequencing in 79 CRCs comprising
      36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16
      paired primary CRCs and liver metastasis. We also performed methylated CpG island
      amplification microarrays (MCAM) in three paired primary and metastatic cancers.
      RESULTS: Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively
      decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs.
      3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic
      tumors were compared, only MGMT methylation was significantly higher in
      metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an
      increase in methylation density rather than frequency in the majority of cases.
      MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic
      samples. The numbers of differentially hypermethylated genes in the liver
      metastases increased with increasing time between resection of the primary and
      resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12
      paired samples showed that most of these increases were not conserved, and could
      be explained by differences in methylation density rather than frequency.
      CONCLUSIONS: Most DNA methylation differences between primary CRCs and matched
      liver metastasis are due to random variation and an increase in DNA methylation
      density rather than de-novo inactivation and silencing. Thus, DNA methylation
      changes occur for the most part before progression to liver metastasis.

PMID- 22132164
TI  - Dyslexic adults can learn from repeated stimulus presentation but have
      difficulties in excluding external noise.
AB  - We examined whether the characteristic impairments of dyslexia are due to a
      deficit in excluding external noise or a deficit in taking advantage of repeated
      stimulus presentation. We compared non-impaired adults and adults with poor
      reading performance on a visual letter detection task that varied two aspects:
      the presence or absence of background visual noise, and a small or large stimulus
      set. There was no interaction between group and stimulus set size, indicating
      that the poor readers took advantage of repeated stimulus presentation as well as
      the non-impaired readers. The poor readers had higher thresholds than non
      impaired readers in the presence of high external noise, but not in the absence
      of external noise. The results support the hypothesis that an external noise
      exclusion deficit, not a perceptual anchoring deficit, impairs reading for
      adults.

PMID- 22132163
TI  - The recognition of N-glycans by the lectin ArtinM mediates cell death of a human
      myeloid leukemia cell line.
AB  - ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus (jackfruit),
      interacts with N-glycosylated receptors on the surface of several cells of
      hematopoietic origin, triggering cell migration, degranulation, and cytokine
      release. Because malignant transformation is often associated with altered
      expression of cell surface glycans, we evaluated the interaction of ArtinM with
      human myelocytic leukemia cells and investigated cellular responses to lectin
      binding. The intensity of ArtinM binding varied across 3 leukemia cell lines:
      NB4>K562>U937. The binding, which was directly related to cell growth
      suppression, was inhibited in the presence of Manalpha1-3(Manalpha1-6)Manbeta1,
      and was reverted in underglycosylated NB4 cells. ArtinM interaction with NB4
      cells induced cell death (IC(50) = 10 ug/mL), as indicated by cell surface
      exposure of phosphatidylserine and disruption of mitochondrial membrane potential
      unassociated with caspase activation or DNA fragmentation. Moreover, ArtinM
      treatment of NB4 cells strongly induced reactive oxygen species generation and
      autophagy, as indicated by the detection of acidic vesicular organelles in the
      treated cells. NB4 cell death was attributed to ArtinM recognition of the
      trimannosyl core of N-glycans containing a beta1,6-GlcNAc branch linked to
      alpha1,6-mannose. This modification correlated with higher levels of N
      acetylglucosaminyltransferase V transcripts in NB4 cells than in K562 or U937
      cells. Our results provide new insights into the potential of N-glycans
      containing a beta1,6-GlcNAc branch linked to alpha1,6-mannose as a novel target
      for anti-leukemia treatment.

PMID- 22132165
TI  - Long-term mortality in patients with tuberculous meningitis: a Danish nationwide
      cohort study.
AB  - BACKGROUND: With high short-term mortality and substantial excess morbidity among
      survivors, tuberculous meningitis (TBM) is the most severe manifestation of extra
      pulmonary tuberculosis (TB). The objective of this study was to assess the long
      term mortality and causes of death in a TBM patient population compared to the
      background population. METHODS: A nationwide cohort study was conducted enrolling
      patients notified with TBM in Denmark from 1972-2008 and alive one year after TBM
      diagnosis. Data was extracted from national registries. From the background
      population we identified a control cohort of individuals matched on gender and
      date of birth. Kaplan-Meier survival curves and Cox regression analysis were used
      to estimate mortality rate ratios (MRR) and analyse causes of death. FINDINGS: A
      total of 55 TBM patients and 550 individuals from the background population were
      included in the study. Eighteen patients (32.7%) and 107 population controls
      (19.5%) died during the observation period. The overall MRR was 1.79 (95%CI: 1.09
      2.95) for TBM patients compared to the population control cohort. TBM patients in
      the age group 31-60 years at time of diagnosis had the highest relative risk of
      death (MRR 2.68; 95%CI 1.34-5.34). The TBM patients had a higher risk of death
      due to infectious disease, but not from other causes of death. CONCLUSION: Adult
      TBM patients have an almost two-fold increased long-term mortality and the excess
      mortality stems from infectious disease related causes of death.

PMID- 22132166
TI  - QTL analysis identifies a modifier locus of aganglionosis in the rat model of
      Hirschsprung disease carrying Ednrb(sl) mutations.
AB  - Hirschsprung disease (HSCR) exhibits complex genetics with incomplete penetrance
      and variable severity thought to result as a consequence of multiple gene
      interactions that modulate the ability of enteric neural crest cells to populate
      the developing gut. As reported previously, when the same null mutation of the
      Ednrb gene, Ednrb(sl), was introgressed into the F344 strain, almost 60% of F344
      Ednrb(sl/sl) pups did not show any symptoms of aganglionosis, appearing healthy
      and normally fertile. These findings strongly suggested that the severity of HSCR
      was affected by strain-specific genetic factor (s). In this study, the genetic
      basis of such large strain differences in the severity of aganglionosis in the
      rat model was studied by whole-genome scanning for quantitative trait loci (QTLs)
      using an intercross of (AGH-Ednrb(sl)*F344-Ednrb(sl)) F(1) with the varying
      severity of aganglionosis. Genome linkage analysis identified one significant QTL
      on chromosome 2 for the severity of aganglionosis. Our QTL analyses using rat
      models of HSCR revealed that multiple genetic factors regulated the severity of
      aganglionosis. Moreover, a known HSCR susceptibility gene, Gdnf, was found in QTL
      that suggested a novel non-coding sequence mutation in GDNF that modifies the
      penetrance and severity of the aganglionosis phenotype in EDNRB-deficient rats. A
      further identification and analysis of responsible genes located on the
      identified QTL could lead to the richer understanding of the genetic basis of
      HSCR development.

PMID- 22132167
TI  - The mechanism of enhanced insulin amyloid fibril formation by NaCl is better
      explained by a conformational change model.
AB  - The high propensity of insulin to fibrillate causes severe biomedical and
      biotechnological complications. Insulin fibrillation studies attain significant
      importance considering the prevalence of diabetes and the requirement of
      functional insulin in each dose. Although studied since the early years of the
      20(th) century, elucidation of the mechanism of insulin fibrillation has not been
      understood completely. We have previously, through several studies, shown that
      insulin hexamer dissociates into monomer that undergoes partial unfolding before
      converting into mature fibrils. In this study we have established that NaCl
      enhances insulin fibrillation mainly due to subtle structural changes and is not
      a mere salt effect. We have carried out studies both in the presence and absence
      of urea and Gdn.HCl and compared the relationship between conformation of insulin
      induced by urea and Gdn.HCl with respect to NaCl at both pH 7.4 (hexamer) and pH
      2 (monomer). Fibril formation was followed with a Thioflavin T assay and
      structural changes were monitored by circular dichroism and size-exclusion
      chromatography. The results show salt-insulin interactions are difficult to
      classify as commonly accepted Debye-Huckel or Hofmeister series interactions but
      instead a strong correlation between the association states and conformational
      states of insulin and their propensity to fibrillate is evident.

PMID- 22132168
TI  - Quality of care in contraceptive services provided to young people in two Ugandan
      districts: a simulated client study.
AB  - BACKGROUND: Low and inconsistent use of contraceptives by young people
      contributes to unintended pregnancies. This study assessed quality of
      contraceptive services for young people aged 15-24 in two rural districts in
      Uganda. METHODS: Five female and two male simulated clients (SCs) interacted with
      128 providers at public, private not-for-profit (PNFP), and private for profit
      (PFP) health facilities. After consultations, SCs were interviewed using a
      structured questionnaire. Six aspects of quality of care (client's needs, choice
      of contraceptive methods, information given to users, client-provider
      interpersonal relations, constellation of services, and continuity mechanisms)
      were assessed. Descriptive statistics and factor analysis were performed.
      RESULTS: Means and categorized quality scores for all aspects of quality were low
      in both public and private facilities. The lowest quality scores were observed in
      PFP, and medium scores in PNFP facilities. The choice of contraceptive methods
      and interpersonal relations quality scores were slightly higher in public
      facilities. Needs assessment scores were highest in PNFP facilities. All
      facilities were classified as having low scores for appropriate constellation of
      services. Information given to users was suboptimal and providers promoted
      specific contraceptive methods. Minority of providers offered preferred method of
      choice and showed respect for privacy. CONCLUSIONS: The quality of contraceptive
      services provided to young people was low. Concurrent quality improvements and
      strengthening of health systems are needed.

PMID- 22132169
TI  - Morphological differentiation may mediate mate-choice between incipient species
      of Anopheles gambiae s.s.
AB  - The M and S molecular forms of Anopheles gambiae s.s. have been considered
      incipient species for more than ten years, yet the mechanism underlying
      assortative mating of these incipient species has remained elusive. The discovery
      of the importance of harmonic convergence of wing beat frequency in mosquito
      mating and its relation to wing size have laid the foundation for exploring
      phenotypic divergence in wing size of wild populations of the two forms. In this
      study, wings from field collected mosquitoes were measured for wing length and
      wing width from two parts of the sympatric distribution, which differ with
      respect to the strength of assortative mating. In Mali, where assortative mating
      is strong, as evidenced by low rates of hybridization, mean wing lengths and wing
      widths were significantly larger than those from Guinea-Bissau. In addition, mean
      wing widths in Mali were significantly different between molecular forms. In
      Guinea-Bissau, assortative mating appears comparatively reduced and wing lengths
      and widths did not differ significantly between molecular forms. The data
      presented in this study support the hypothesis that wing beat frequency may
      mediate assortative mating in the incipient species of A. gambiae and represent
      the first documentation of a morphological difference between the M and S
      molecular forms.

PMID- 22132170
TI  - Learned value magnifies salience-based attentional capture.
AB  - Visual attention is captured by physically salient stimuli (termed salience-based
      attentional capture), and by otherwise task-irrelevant stimuli that contain goal
      related features (termed contingent attentional capture). Recently, we reported
      that physically nonsalient stimuli associated with value through reward learning
      also capture attention involuntarily (Anderson, Laurent, & Yantis, PNAS, 2011).
      Although it is known that physical salience and goal-relatedness both influence
      attentional priority, it is unknown whether or how attentional capture by a
      salient stimulus is modulated by its associated value. Here we show that a
      physically salient, task-irrelevant distractor previously associated with a large
      reward slows visual search more than an equally salient distractor previously
      associated with a smaller reward. This magnification of salience-based
      attentional capture by learned value extinguishes over several hundred trials.
      These findings reveal a broad influence of learned value on involuntary
      attentional capture.

PMID- 22132171
TI  - A practical approach to T-cell receptor cloning and expression.
AB  - Although cloning and expression of T-cell Receptors (TcRs) has been performed for
      almost two decades, these procedures are still challenging. For example, the use
      of T-cell clones that have undergone limited expansion as starting material to
      limit the loss of interesting TcRs, must be weighed against the introduction of
      mutations by excess PCR cycles. The recent interest in using specific TcRs for
      cancer immunotherapy has, however, increased the demand for practical and robust
      methods to rapidly clone and express TcRs. Two main technologies for TcR cloning
      have emerged; the use of a set of primers specifically annealing to all known TcR
      variable domains, and 5'-RACE amplification. We here present an improved 5'-RACE
      protocol that represents a fast and reliable way to identify a TcR from 10(5)
      cells only, making TcR cloning feasible without a priori knowledge of the
      variable domain sequence. We further present a detailed procedure for the
      subcloning of TcRalpha and beta chains into an expression system. We show that a
      recombination-based cloning protocol facilitates simple and rapid transfer of the
      TcR transgene into different expression systems. The presented comprehensive
      method can be performed in any laboratory with standard equipment and with a
      limited amount of starting material. We finally exemplify the straightforwardness
      and reliability of our procedure by cloning and expressing several MART-1
      specific TcRs and demonstrating their functionality.

PMID- 22132172
TI  - Survival of influenza A(H1N1) on materials found in households: implications for
      infection control.
AB  - BACKGROUND: The majority of influenza transmission occurs in homes, schools and
      workplaces, where many frequently touched communal items are situated. However
      the importance of transmission via fomites is unclear since few data exist on the
      survival of virus on commonly touched surfaces. We therefore measured the
      viability over time of two H1N1 influenza strains applied to a variety of
      materials commonly found in households and workplaces. METHODOLOGY AND PRINCIPAL
      FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic
      H1N1) viruses were inoculated onto a wide range of surfaces used in home and work
      environments, then sampled at set times following incubation at stabilised
      temperature and humidity. Virus genome was measured by RT-PCR; plaque assay (for
      PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the
      survival of viable virus. CONCLUSIONS/SIGNIFICANCE: The genome of either virus
      could be detected on most surfaces 24 h after application with relatively little
      drop in copy number, with the exception of unsealed wood surfaces. In contrast,
      virus viability dropped much more rapidly. Live virus was recovered from most
      surfaces tested four hours after application and from some non-porous materials
      after nine hours, but had fallen below the level of detection from all surfaces
      at 24 h. We conclude that influenza A transmission via fomites is possible but
      unlikely to occur for long periods after surface contamination (unless re
      inoculation occurs). In situations involving a high probability of influenza
      transmission, our data suggest a hierarchy of priorities for surface
      decontamination in the multi-surface environments of home and hospitals.

PMID- 22132173
TI  - Human papillomavirus persistence in young unscreened women, a prospective cohort
      study.
AB  - OBJECTIVE: To evaluate hr-HPV persistence and associated risk factors in a
      prospective cohort of young unscreened women. Additionally, the relation between
      hr-HPV status and cytology/histology results is examined. METHODS AND PRINCIPAL
      FINDINGS: Two year follow-up of 235 out of 2065 young women (18-29 years),
      participating in a large, one year epidemiological study, with questionnaires,
      self-collected cervico-vaginal samples (Vibabrush), and SPF(10)LiPA for HPV
      detection. Only women hr-HPV positive at sample month 12 were invited for a
      second year of follow-up. After study follow-up, available cytology/histology
      data were requested from PALGA (the national network and registry of histo- and
      cytopathology in The Netherlands). These data were compared with available
      cytology/histology data of the month 12 hr-HPV negative women from the same
      cohort. 44.1% of the hr-HPV types detected at study month 12, persisted during
      follow-up. HPV types 45, 31, 16 and 18 were most likely to persist with
      percentages of 60.0%, 56.8%, 54.4%,and 50.0%, respectively. Compared to newly
      detected infections at month 12, infections present since 6 months or baseline
      had an increased risk to persist (OR 3.09 [95% CI: 1.74-5.51] and OR 4.99 [95%
      CI: 2.67-9.32], respectively). Other co-factors influencing persistence were,
      multiple HPV infections, smoking and multiple lifetime sexual partners. The
      percentage of women with a HSIL/CIN2+ (12.1%) in the persistent HPV group, was
      not significantly different (p = 0.107) from the 5.3% of the women who cleared
      the hr-HPV infection, but was significantly (p 0.000) higher than to the 1.6% of
      women in the hr-HPV negative control group. CONCLUSION: We showed that HPV
      genotype, multiple infections, smoking, and multiple lifetime sexual partners are
      co-factors that increase the risk of hr-HPV persistency. Most importantly, we
      showed that hr-HPV infections are more likely to persist the longer they have
      been present and that women with a persistent hr-HPV infection have a high risk
      of HSIL/CIN2+ development.

PMID- 22132174
TI  - A contracted DNA repeat in LHX3 intron 5 is associated with aberrant splicing and
      pituitary dwarfism in German shepherd dogs.
AB  - Dwarfism in German shepherd dogs is due to combined pituitary hormone deficiency
      of unknown genetic cause. We localized the recessively inherited defect by a
      genome wide approach to a region on chromosome 9 with a lod score of 9.8. The
      region contains LHX3, which codes for a transcription factor essential for
      pituitary development. Dwarfs have a deletion of one of six 7 bp repeats in
      intron 5 of LHX3, reducing the intron size to 68 bp. One dwarf was compound
      heterozygous for the deletion and an insertion of an asparagine residue in the
      DNA-binding homeodomain of LHX3, suggesting involvement of the gene in the
      disorder. An exon trapping assay indicated that the shortened intron is not
      spliced efficiently, probably because it is too small. We applied bisulfite
      conversion of cytosine to uracil in RNA followed by RT-PCR to analyze the
      splicing products. The aberrantly spliced RNA molecules resulted from either
      skipping of exon 5 or retention of intron 5. The same splicing defects were
      observed in cDNA derived from the pituitary of dwarfs. A survey of similarly
      mutated introns suggests that there is a minimal distance requirement between the
      splice donor and branch site of 50 nucleotides. In conclusion, a contraction of a
      DNA repeat in intron 5 of canine LHX3 leads to deficient splicing and is
      associated with pituitary dwarfism.

PMID- 22132175
TI  - Normalization of high dimensional genomics data where the distribution of the
      altered variables is skewed.
AB  - Genome-wide analysis of gene expression or protein binding patterns using
      different array or sequencing based technologies is now routinely performed to
      compare different populations, such as treatment and reference groups. It is
      often necessary to normalize the data obtained to remove technical variation
      introduced in the course of conducting experimental work, but standard
      normalization techniques are not capable of eliminating technical bias in cases
      where the distribution of the truly altered variables is skewed, i.e. when a
      large fraction of the variables are either positively or negatively affected by
      the treatment. However, several experiments are likely to generate such skewed
      distributions, including ChIP-chip experiments for the study of chromatin, gene
      expression experiments for the study of apoptosis, and SNP-studies of copy number
      variation in normal and tumour tissues. A preliminary study using spike-in array
      data established that the capacity of an experiment to identify altered variables
      and generate unbiased estimates of the fold change decreases as the fraction of
      altered variables and the skewness increases. We propose the following work-flow
      for analyzing high-dimensional experiments with regions of altered variables: (1)
      Pre-process raw data using one of the standard normalization techniques. (2)
      Investigate if the distribution of the altered variables is skewed. (3) If the
      distribution is not believed to be skewed, no additional normalization is needed.
      Otherwise, re-normalize the data using a novel HMM-assisted normalization
      procedure. (4) Perform downstream analysis. Here, ChIP-chip data and simulated
      data were used to evaluate the performance of the work-flow. It was found that
      skewed distributions can be detected by using the novel DSE-test (Detection of
      Skewed Experiments). Furthermore, applying the HMM-assisted normalization to
      experiments where the distribution of the truly altered variables is skewed
      results in considerably higher sensitivity and lower bias than can be attained
      using standard and invariant normalization methods.

PMID- 22132176
TI  - Phenotypes of non-attached Pseudomonas aeruginosa aggregates resemble surface
      attached biofilm.
AB  - For a chronic infection to be established, bacteria must be able to cope with
      hostile conditions such as low iron levels, oxidative stress, and clearance by
      the host defense, as well as antibiotic treatment. It is generally accepted that
      biofilm formation facilitates tolerance to these adverse conditions. However,
      microscopic investigations of samples isolated from sites of chronic infections
      seem to suggest that some bacteria do not need to be attached to surfaces in
      order to establish chronic infections. In this study we employed scanning
      electron microscopy, confocal laser scanning microscopy, RT-PCR as well as
      traditional culturing techniques to study the properties of Pseudomonas
      aeruginosa aggregates. We found that non-attached aggregates from stationary
      phase cultures have comparable growth rates to surface attached biofilms. The
      growth rate estimations indicated that, independently of age, both aggregates and
      flow-cell biofilm had the same slow growth rate as a stationary phase shaking
      cultures. Internal structures of the aggregates matrix components and their
      capacity to survive otherwise lethal treatments with antibiotics (referred to as
      tolerance) and resistance to phagocytes were also found to be strikingly similar
      to flow-cell biofilms. Our data indicate that the tolerance of both biofilms and
      non-attached aggregates towards antibiotics is reversible by physical disruption.
      We provide evidence that the antibiotic tolerance is likely to be dependent on
      both the physiological states of the aggregates and particular matrix components.
      Bacterial surface-attachment and subsequent biofilm formation are considered
      hallmarks of the capacity of microbes to cause persistent infections. We have
      observed non-attached aggregates in the lungs of cystic fibrosis patients; otitis
      media; soft tissue fillers and non-healing wounds, and we propose that aggregated
      cells exhibit enhanced survival in the hostile host environment, compared with
      non-aggregated bacterial populations.

PMID- 22132177
TI  - Liver enzymes: interaction analysis of smoking with alcohol consumption or BMI,
      comparing AST and ALT to gamma-GT.
AB  - BACKGROUND: A detrimental interaction between smoking and alcohol consumption
      with respect serum gamma-glutamyltransferase (gamma-GT) has recently been
      described. The underlying mechanisms remain unknown. The present work aimed to
      provide further insights by examining similar interactions pertaining to
      aspartate and alanine transaminase (AST, ALT), routine liver markers less prone
      to enzyme induction. METHODOLOGY/PRINCIPAL FINDINGS: The present cross-sectional
      analysis was based on records from routine occupational health examinations of
      15,281 male employees predominantly of the construction industry, conducted from
      1986 to 1992 in Southern Germany. Associations of smoking intensity with log
      transformed activities of gamma-GT, AST, and ALT were examined in regression
      models adjusted for potential confounders and including an interaction of smoking
      with alcohol consumption or body mass index (BMI). Statistically significant
      interactions of smoking were observed with both alcohol consumption (AST and ALT,
      each with P<0.0001) and BMI (AST only, P<0.0001). The interactions all were in
      the same directions as for gamma-GT, i.e. synergistic with alcohol and opposite
      with BMI. CONCLUSION: The patterns of interaction between smoking and alcohol
      consumption or BMI with respect to AST and ALT resembled those observed for gamma
      GT. This renders enzyme induction a less probable mechanism for these
      associations, whereas it might implicate exacerbated hepatocellular vulnerability
      and injury.

PMID- 22132178
TI  - Generation of induced pluripotent stem cells from CD34+ cells across blood drawn
      from multiple donors with non-integrating episomal vectors.
AB  - The methodology to create induced pluripotent stem cells (iPSCs) affords the
      opportunity to generate cells specific to the individual providing the host
      tissue. However, existing methods of reprogramming as well as the types of source
      tissue have significant limitations that preclude the ability to generate iPSCs
      in a scalable manner from a readily available tissue source. We present the first
      study whereby iPSCs are derived in parallel from multiple donors using episomal,
      non-integrating, oriP/EBNA1-based plasmids from freshly drawn blood.
      Specifically, successful reprogramming was demonstrated from a single vial of
      blood or less using cells expressing the early lineage marker CD34 as well as
      from unpurified peripheral blood mononuclear cells. From these experiments, we
      also show that proliferation and cell identity play a role in the number of iPSCs
      per input cell number. Resulting iPSCs were further characterized and deemed free
      of transfected DNA, integrated transgene DNA, and lack detectable gene
      rearrangements such as those within the immunoglobulin heavy chain and T cell
      receptor loci of more differentiated cell types. Furthermore, additional
      improvements were made to incorporate completely defined media and matrices in an
      effort to facilitate a scalable transition for the production of clinic-grade
      iPSCs.

PMID- 22132179
TI  - Switch of voltage-gated K+ channel expression in the plasma membrane of
      chondrogenic cells affects cytosolic Ca2+-oscillations and cartilage formation.
AB  - BACKGROUND: Understanding the key elements of signaling of chondroprogenitor
      cells at the earliest steps of differentiation may substantially improve our
      opportunities for the application of mesenchymal stem cells in cartilage tissue
      engineering, which is a promising approach of regenerative therapy of joint
      diseases. Ion channels, membrane potential and Ca(2+)-signaling are important
      regulators of cell proliferation and differentiation. Our aim was to identify
      such plasma membrane ion channels involved in signaling during chondrogenesis,
      which may serve as specific molecular targets for influencing chondrogenic
      differentiation and ultimately cartilage formation. METHODOLOGY/PRINCIPAL
      FINDINGS: Using patch-clamp, RT-PCR and Western-blot experiments, we found that
      chondrogenic cells in primary micromass cell cultures obtained from embryonic
      chicken limb buds expressed voltage-gated Na(V)1.4, K(V)1.1, K(V)1.3 and K(V)4.1
      channels, although K(V)1.3 was not detectable in the plasma membrane.
      Tetrodotoxin (TTX), the inhibitor of Na(V)1.4 channels, had no effect on
      cartilage formation. In contrast, presence of 20 mM of the K(+) channel blocker
      tetraethyl-ammonium (TEA) during the time-window of the final commitment of
      chondrogenic cells reduced K(V) currents (to 27+/-3% of control), cell
      proliferation (thymidine incorporation: to 39+/-4.4% of control), expression of
      cartilage-specific genes and consequently, cartilage formation (metachromasia: to
      18.0+/-6.4% of control) and also depolarized the membrane potential (by 9.3+/-2.1
      mV). High-frequency Ca(2+)-oscillations were also suppressed by 10 mM TEA
      (confocal microscopy: frequency to 8.5+/-2.6% of the control). Peak expression of
      TEA-sensitive K(V)1.1 in the plasma membrane overlapped with this period.
      Application of TEA to differentiated chondrocytes, mainly expressing the TEA
      insensitive K(V)4.1 did not affect cartilage formation. CONCLUSIONS/SIGNIFICANCE:
      These data demonstrate that the differentiation and proliferation of chondrogenic
      cells depend on rapid Ca(2+)-oscillations, which are modulated by K(V)-driven
      membrane potential changes. K(V)1.1 function seems especially critical during the
      final commitment period. We show the critical role of voltage-gated cation
      channels in the differentiation of non-excitable cells with potential therapeutic
      use.

PMID- 22132180
TI  - Energy restriction during childhood and early adulthood and ovarian cancer risk.
AB  - Dietary energy restriction may protect against cancer. In parts of The
      Netherlands, mostly in larger cities, periods of chronically impaired nutrition
      and even severe famine (Hunger Winter 1944-1945) existed during the 1930s and
      World War II (1940-1945). We studied the association between energy restriction
      during childhood and early adulthood on the risk of ovarian cancer later in life.
      In 1986, the Netherlands Cohort Study was initiated. A self-administered
      questionnaire on dietary habits and other cancer risk factors was completed by
      62,573 women aged 55-69 years at baseline. Follow-up for cancer was established
      by record linkage to the Netherlands Cancer Registry. After 16.3 years of follow
      up, 364 invasive epithelial ovarian cancer cases and 2220 subcohort members
      (sampled from the total cohort directly after baseline) with complete information
      confounders were available for case-cohort analyses. In multivariable analysis,
      ovarian cancer risk was lower for participants with an unemployed father during
      the 1930s (Hazard Ratio (HR), 0.70; 95% Confidence Interval (CI), 0.47-1.06)
      compared to participants with an employed father as well as for participants
      living in a city during World War II (HR, 0.69; 95% CI, 0.54-0.90) compared to
      participants living in the country-side. Residence in a Western City during the
      famine (Hunger Winter) was not associated with a decreased risk. Our results show
      a relation between proxy variables for modest energy restriction over a longer
      period of time during childhood or early adulthood and a reduced ovarian cancer
      risk.

PMID- 22132181
TI  - Lysate of probiotic Lactobacillus casei DN-114 001 ameliorates colitis by
      strengthening the gut barrier function and changing the gut microenvironment.
AB  - BACKGROUND: Probiotic bacteria can be used for the prevention and treatment of
      human inflammatory diseases including inflammatory bowel diseases (IBD). However,
      the nature of active components and exact mechanisms of this beneficial effects
      have not been fully elucidated. Our aim was to investigate if lysate of probiotic
      bacterium L. casei DN-114 001 (Lc) could decrease the severity of intestinal
      inflammation in a murine model of IBD. METHODOLOGY/PRINCIPAL FINDINGS: The
      preventive effect of oral administration of Lc significantly reduces the severity
      of acute dextran sulfate sodium (DSS) colitis in BALB/c but not in SCID mice. In
      order to analyze how this beneficial effect interferes with well-known phases of
      intestinal inflammation pathogenesis in vivo and in vitro, we evaluated
      intestinal permeability using the FITC-labeled dextran method and analysed tight
      junction proteins expression by immunofluorescence and PCR. We also measured
      CD4(+)FoxP3(+) regulatory T cells proportion by FACS analysis, microbiota
      composition by pyrosequencing, and local cytokine production by ELISA. Lc leads
      to a significant protection against increased intestinal permeability and barrier
      dysfunction shown by preserved ZO-1 expression. We found that the Lc treatment
      increases the numbers of CD4(+)FoxP3(+) regulatory T cells in mesenteric lymph
      nodes (MLN), decreases production of pro-inflammatory cytokines TNF-alpha and IFN
      gamma, and anti-inflammatory IL-10 in Peyer's patches and large intestine, and
      changes the gut microbiota composition. Moreover, Lc treatment prevents
      lipopolysaccharide-induced TNF-alpha expression in RAW 264.7 cell line by down
      regulating the NF-kappaB signaling pathway. CONCLUSION/SIGNIFICANCE: Our study
      provided evidence that even non-living probiotic bacteria can prevent the
      development of severe forms of intestinal inflammation by strengthening the
      integrity of intestinal barrier and modulation of gut microenvironment.

PMID- 22132182
TI  - Involvement of histone acetylation of Sox17 and Foxa2 promoters during mouse
      definitive endoderm differentiation revealed by microRNA profiling.
AB  - Generation of hepatocyte from embryonic stem cells (ESCs) holds great promise for
      hepatocyte replacement therapy to treat liver diseases. Achieving high efficiency
      of directed differentiation of ESCs to hepatocyte is of critical importance.
      Previously, Wnt3a has been reported to promote Activin A-induced human definitive
      endoderm (DE) differentiation, the early stage of hepatocyte differentiation.
      However, the underlying molecular mechanisms are not clear. Growing evidence
      demonstrated that microRNAs (miRNAs) are key regulators involved in various
      important biological processes including the regulation of stem cell
      differentiation. In the present study, we profiled genome wide miRNA expression
      during Wnt3a and Activin A induced mouse DE differentiation. We uncovered
      distinct miRNA expression patterns during DE differentiation with the
      identification of a subset of miRNAs whose expression is synergistically
      regulated by Wnt3a/Activin A treatment at different stages of DE differentiation.
      Forced expression of a pool of such synergistically regulated miRNAs alone could
      partially promote DE differentiation, indicating a regulatory role of them. Using
      TargetScan and GeneGO pathway analyses, the synergistically regulated miRNAs are
      predicted to regulate key pathways involved in DE differentiation; among them
      includes the regulation of histone acetylation. Consistently, Wnt3a and Activin A
      treatment increased global histone acetylation which can be partially mimicked by
      over expression of the pooled miRNAs. Chromatin IP (ChIP) experiments
      demonstrated that the promoter regions of Sox17 and Foxa2 are subjected to
      histone acetylation regulation. Administration of Hdac inhibitors greatly
      augmented DE differentiation. Our data uncovered a novel epigenetic mechanism of
      Wnt3a and Activin A induced DE differentiation, whereby the treatment of growth
      factors induced histone acetylation at least in part by the regulation of miRNA
      expression.

PMID- 22132183
TI  - Transcriptomic analyses during the transition from biomass production to lipid
      accumulation in the oleaginous yeast Yarrowia lipolytica.
AB  - We previously developed a fermentation protocol for lipid accumulation in the
      oleaginous yeast Y. lipolytica. This process was used to perform transcriptomic
      time-course analyses to explore gene expression in Y. lipolytica during the
      transition from biomass production to lipid accumulation. In this experiment, a
      biomass concentration of 54.6 g(CDW)/l, with 0.18 g/g(CDW) lipid was obtained in
      ca. 32 h, with low citric acid production. A transcriptomic profiling was
      performed on 11 samples throughout the fermentation. Through statistical
      analyses, 569 genes were highlighted as differentially expressed at one point
      during the time course of the experiment. These genes were classified into 9
      clusters, according to their expression profiles. The combination of macroscopic
      and transcriptomic profiles highlighted 4 major steps in the culture: (i) a
      growth phase, (ii) a transition phase, (iii) an early lipid accumulation phase,
      characterized by an increase in nitrogen metabolism, together with strong
      repression of protein production and activity; (iv) a late lipid accumulation
      phase, characterized by the rerouting of carbon fluxes within cells. This study
      explores the potential of Y. lipolytica as an alternative oil producer, by
      identifying, at the transcriptomic level, the genes potentially involved in the
      metabolism of oleaginous species.

PMID- 22132184
TI  - The communicability of graphical alternatives to tabular displays of statistical
      simulation studies.
AB  - Simulation studies are often used to assess the frequency properties and
      optimality of statistical methods. They are typically reported in tables, which
      may contain hundreds of figures to be contrasted over multiple dimensions. To
      assess the degree to which these tables are fit for purpose, we performed a
      randomised cross-over experiment in which statisticians were asked to extract
      information from (i) such a table sourced from the literature and (ii) a
      graphical adaptation designed by the authors, and were timed and assessed for
      accuracy. We developed hierarchical models accounting for differences between
      individuals of different experience levels (under- and post-graduate), within
      experience levels, and between different table-graph pairs. In our experiment,
      information could be extracted quicker and, for less experienced participants,
      more accurately from graphical presentations than tabular displays. We also
      performed a literature review to assess the prevalence of hard-to-interpret
      design features in tables of simulation studies in three popular statistics
      journals, finding that many are presented innumerately. We recommend simulation
      studies be presented in graphical form.

PMID- 22132185
TI  - Association between regulator of G protein signaling 9-2 and body weight.
AB  - Regulator of G protein signaling 9-2 (RGS9-2) is a protein that is highly
      enriched in the striatum, a brain region that mediates motivation, movement and
      reward responses. We identified a naturally occurring 5 nucleotide deletion
      polymorphism in the human RGS9 gene and found that the mean body mass index (BMI)
      of individuals with the deletion was significantly higher than those without. A
      splicing reporter minigene assay demonstrated that the deletion had the potential
      to significantly decrease the levels of correctly spliced RGS9 gene product. We
      measured the weights of rats after virally transduced overexpression of RGS9-2 or
      the structurally related RGS proteins, RGS7, or RGS11, in the nucleus accumbens
      (NAc) and observed a reduction in body weight after overexpression of RGS9-2 but
      not RGS7 or 11. Conversely, we found that the RGS9 knockout mice were heavier
      than their wild-type littermates and had significantly higher percentages of
      abdominal fat. The constituent adipocytes were found to have a mean cross
      sectional area that was more than double that of corresponding cells from wild
      type mice. However, food intake and locomotion were not significantly different
      between the two strains. These studies with humans, rats and mice implicate RGS9
      2 as a factor in regulating body weight.

PMID- 22132186
TI  - The heritability of amyotrophic lateral sclerosis in a clinically ascertained
      United States research registry.
AB  - BACKGROUND: The genetic basis of amyotrophic lateral sclerosis (ALS) is not
      entirely clear. While there are families with rare highly penetrant mutations in
      Cu/Zn superoxide dismutase 1 and several other genes that cause apparent
      Mendelian inheritance of the disease, most ALS occurs in families without another
      affected individual. However, twin studies suggest that all ALS has a substantial
      genetic basis. Herein, we estimate the genetic contribution to ALS in a
      clinically ascertained case series from the United States. METHODOLOGY/PRINCIPAL
      FINDINGS: We used the database of the Emory ALS Center to ascertain individuals
      with ALS along with their family histories to determine the concordance among
      parents and offspring for the disease. We found that concordance for all parent
      offspring pairs was low (<2%). With this concordance we found that ALS
      heritability, or the proportion of the disease explained by genetic factors, is
      between 40 and 45% for all likely estimates of ALS lifetime prevalence.
      CONCLUSIONS/SIGNIFICANCE: We found the lifetime risk of ALS is 1.1% in first
      degree relatives of those with ALS. Environmental and genetic factors appear
      nearly equally important for the development of ALS.

PMID- 22132187
TI  - Identification of cytotoxic drugs that selectively target tumor cells with MYC
      overexpression.
AB  - Expression of MYC is deregulated in a wide range of human cancers, and is often
      associated with aggressive disease and poorly differentiated tumor cells.
      Identification of compounds with selectivity for cells overexpressing MYC would
      hence be beneficial for the treatment of these tumors. For this purpose we used
      cell lines with conditional MYCN or c-MYC expression, to screen a library of 80
      conventional cytotoxic compounds for their ability to reduce tumor cell viability
      and/or growth in a MYC dependent way. We found that 25% of the studied compounds
      induced apoptosis and/or inhibited proliferation in a MYC-specific manner. The
      activities of the majority of these were enhanced both by c-MYC or MYCN over
      expression. Interestingly, these compounds were acting on distinct cellular
      targets, including microtubules (paclitaxel, podophyllotoxin, vinblastine) and
      topoisomerases (10-hydroxycamptothecin, camptothecin, daunorubicin, doxorubicin,
      etoposide) as well as DNA, RNA and protein synthesis and turnover (anisomycin,
      aphidicholin, gliotoxin, MG132, methotrexate, mitomycin C). Our data indicate
      that MYC overexpression sensitizes cells to disruption of specific pathways and
      that in most cases c-MYC and MYCN overexpression have similar effects on the
      responses to cytotoxic compounds. Treatment of the cells with topoisomerase I
      inhibitors led to down-regulation of MYC protein levels, while doxorubicin and
      the small molecule MYRA-A was found to disrupt MYC-Max interaction. We conclude
      that the MYC pathway is only targeted by a subset of conventional cytotoxic drugs
      currently used in the clinic. Elucidating the mechanisms underlying their
      specificity towards MYC may be of importance for optimizing treatment of tumors
      with MYC deregulation. Our data also underscores that MYC is an attractive target
      for novel therapies and that cellular screenings of chemical libraries can be a
      powerful tool for identifying compounds with a desired biological activity.

PMID- 22132189
TI  - Heterogeneous light supply affects growth and biomass allocation of the
      understory fern Diplopterygium glaucum at high patch contrast.
AB  - Spatial heterogeneity in resource supply is common and responses to heterogeneous
      resource supply have been extensively documented in clonal angiosperms but not in
      pteridophytes. To test the hypotheses that clonal integration can modify
      responses of pteridophytes to heterogeneous resource supply and the integration
      effect is larger at higher patch contrast, we conducted a field experiment with
      three homogeneous and two heterogeneous light treatments on the rhizomatous,
      understory fern Diplopterygium glaucum in an evergreen broad-leaved forest in
      East China. In homogeneous treatments, all D. glaucum ramets in 1.5 m*1.5 m units
      were subjected to 10, 40 and 100% natural light, respectively. In the
      heterogeneous treatment of low patch contrast, ramets in the central 0.5 m*0.5 m
      plots of the units were subjected to 40% natural light and their interconnected
      ramets in the surrounding area of the units to 100%; in the heterogeneous
      treatment of high patch contrast, ramets in the central plots were subjected to
      10% natural light and those in the surrounding area to 100%. In the homogeneous
      treatments, biomass and number of living ramets in the central plots decreased
      and number of dead ramets increased with decreasing light supply. At low contrast
      heterogeneous light supply did not affect performance or biomass allocation of D.
      glaucum in the central plots, but at high contrast it increased lamina biomass
      and number of living ramets older than annual and modified biomass allocation to
      lamina and rhizome. Thus, clonal integration can affect responses of understory
      ferns to heterogeneous light supply and ramets in low light patches can be
      supported by those in high light. The results also suggest that effects of clonal
      integration depend on the degree of patch contrast and a significant integration
      effect may be found only under a relatively high patch contrast.

PMID- 22132188
TI  - Modeling of human prokineticin receptors: interactions with novel small-molecule
      binders and potential off-target drugs.
AB  - BACKGROUND AND MOTIVATION: The Prokineticin receptor (PKR) 1 and 2 subtypes are
      novel members of family A GPCRs, which exhibit an unusually high degree of
      sequence similarity. Prokineticins (PKs), their cognate ligands, are small
      secreted proteins of ~80 amino acids; however, non-peptidic low-molecular weight
      antagonists have also been identified. PKs and their receptors play important
      roles under various physiological conditions such as maintaining circadian rhythm
      and pain perception, as well as regulating angiogenesis and modulating immunity.
      Identifying binding sites for known antagonists and for additional potential
      binders will facilitate studying and regulating these novel receptors. Blocking
      PKRs may serve as a therapeutic tool for various diseases, including acute pain,
      inflammation and cancer. METHODS AND RESULTS: Ligand-based pharmacophore models
      were derived from known antagonists, and virtual screening performed on the
      DrugBank dataset identified potential human PKR (hPKR) ligands with novel
      scaffolds. Interestingly, these included several HIV protease inhibitors for
      which endothelial cell dysfunction is a documented side effect. Our results
      suggest that the side effects might be due to inhibition of the PKR signaling
      pathway. Docking of known binders to a 3D homology model of hPKR1 is in agreement
      with the well-established canonical TM-bundle binding site of family A GPCRs.
      Furthermore, the docking results highlight residues that may form specific
      contacts with the ligands. These contacts provide structural explanation for the
      importance of several chemical features that were obtained from the structure
      activity analysis of known binders. With the exception of a single loop residue
      that might be perused in the future for obtaining subtype-specific regulation,
      the results suggest an identical TM-bundle binding site for hPKR1 and hPKR2. In
      addition, analysis of the intracellular regions highlights variable regions that
      may provide subtype specificity.

PMID- 22132190
TI  - Selenomethionine incorporation into amyloid sequences regulates fibrillogenesis
      and toxicity.
AB  - BACKGROUND: The capacity of a polypeptide chain to engage in an amyloid formation
      process and cause a conformational disease is contained in its sequence. Some of
      the sequences undergoing fibrillation contain critical methionine (Met) residues
      which in vivo can be synthetically substituted by selenomethionine (SeM) and
      alter their properties. METHODOLOGY/PRINCIPAL FINDINGS: Using peptide synthesis,
      biophysical techniques and cell viability determinations we have studied the
      effect of the substitution of methionine (Met) by selenomethionine (SeM) on the
      fibrillogenesis and toxic properties of Abeta40 and HuPrP(106-140). We have found
      that the effects display site-specificity and vary from inhibition of
      fibrillation and decreased toxicity ([SeM(35)]Abeta40, [SeM(129)]HuPrP(106-140)
      and [SeM(134)]HuPrP(106-140)), retarded assembly, modulation of polymer shape and
      retention of toxicity ([SeM(112)]HuPrP(106-140) to absence of effects
      ([SeM(109)]HuPrP(106-140)). CONCLUSIONS/SIGNIFICANCE: This work provides direct
      evidence that the substitution of Met by SeM in proamyloid sequences has a major
      impact on their self-assembly and toxic properties, suggesting that the SeM pool
      can play a major role in dictating the allowance and efficiency of a polypeptide
      chain to undergo toxic polymerization.

PMID- 22132191
TI  - Novel tools for conservation genomics: comparing two high-throughput approaches
      for SNP discovery in the transcriptome of the European hake.
AB  - The growing accessibility to genomic resources using next-generation sequencing
      (NGS) technologies has revolutionized the application of molecular genetic tools
      to ecology and evolutionary studies in non-model organisms. Here we present the
      case study of the European hake (Merluccius merluccius), one of the most
      important demersal resources of European fisheries. Two sequencing platforms, the
      Roche 454 FLX (454) and the Illumina Genome Analyzer (GAII), were used for Single
      Nucleotide Polymorphisms (SNPs) discovery in the hake muscle transcriptome. De
      novo transcriptome assembly into unique contigs, annotation, and in silico SNP
      detection were carried out in parallel for 454 and GAII sequence data. High
      throughput genotyping using the Illumina GoldenGate assay was performed for
      validating 1,536 putative SNPs. Validation results were analysed to compare the
      performances of 454 and GAII methods and to evaluate the role of several
      variables (e.g. sequencing depth, intron-exon structure, sequence quality and
      annotation). Despite well-known differences in sequence length and throughput,
      the two approaches showed similar assay conversion rates (approximately 43%) and
      percentages of polymorphic loci (67.5% and 63.3% for GAII and 454, respectively).
      Both NGS platforms therefore demonstrated to be suitable for large scale
      identification of SNPs in transcribed regions of non-model species, although the
      lack of a reference genome profoundly affects the genotyping success rate. The
      overall efficiency, however, can be improved using strict quality and filtering
      criteria for SNP selection (sequence quality, intron-exon structure, target
      region score).

PMID- 22132192
TI  - Genome-wide identification of microRNAs in response to low nitrate availability
      in maize leaves and roots.
AB  - BACKGROUND: Nitrate is the major source of nitrogen available for many crop
      plants and is often the limiting factor for plant growth and agricultural
      productivity especially for maize. Many studies have been done identifying the
      transcriptome changes under low nitrate conditions. However, the microRNAs
      (miRNAs) varied under nitrate limiting conditions in maize has not been reported.
      MiRNAs play important roles in abiotic stress responses and nutrient deprivation.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the SmartArrayTM and
      GeneChip(r) microarray systems to perform a genome-wide search to detect miRNAs
      responding to the chronic and transient nitrate limiting conditions in maize.
      Nine miRNA families (miR164, miR169, miR172, miR397, miR398, miR399, miR408,
      miR528, and miR827) were identified in leaves, and nine miRNA families (miR160,
      miR167, miR168, miR169, miR319, miR395, miR399, miR408, and miR528) identified in
      roots. They were verified by real time stem loop RT-PCR, and some with additional
      time points of nitrate limitation. The miRNAs identified showed overlapping or
      unique responses to chronic and transient nitrate limitation, as well as tissue
      specificity. The potential target genes of these miRNAs in maize were identified.
      The expression of some of these was examined by qRT-PCR. The potential function
      of these miRNAs in responding to nitrate limitation is described.
      CONCLUSIONS/SIGNIFICANCE: Genome-wide miRNAs responding to nitrate limiting
      conditions in maize leaves and roots were identified. This provides an insight
      into the timing and tissue specificity of the transcriptional regulation to low
      nitrate availability in maize. The knowledge gained will help understand the
      important roles miRNAs play in maize responding to a nitrogen limiting
      environment and eventually develop strategies for the improvement of maize
      genetics.

PMID- 22132193
TI  - Transcriptional repression of Cdc25B by IER5 inhibits the proliferation of
      leukemic progenitor cells through NF-YB and p300 in acute myeloid leukemia.
AB  - The immediately-early response gene 5 (IER5) has been reported to be induced by
      gamma-ray irradiation and to play a role in the induction of cell death caused by
      radiation. We previously identified IER5 as one of the 2,3,4-tribromo-3-methyl-1
      phenylphospholane 1-oxide (TMPP)-induced transcriptional responses in AML cells,
      using microarrays that encompassed the entire human genome. However, the
      biochemical pathway and mechanisms of IER5 function in regulation of the cell
      cycle remain unclear. In this study, we investigated the involvement of IER5 in
      the cell cycle and in cell proliferation of acute myeloid leukemia (AML) cells.
      We found that the over-expression of IER5 in AML cell lines and in AML-derived
      ALDH(hi) (High Aldehyde Dehydrogenase activity)/CD34(+) cells inhibited their
      proliferation compared to control cells, through induction of G2/M cell cycle
      arrest and a decrease in Cdc25B expression. Moreover, the over-expression of IER5
      reduced colony formation of AML-derived ALDH(hi)/CD34(+) cells due to a decrease
      in Cdc25B expression. In addition, over-expression of Cdc25B restored TMPP
      inhibitory effects on colony formation in IER5-suppressed AML-derived
      ALDH(hi)/CD34(+) cells. Furthermore, the IER5 reduced Cdc25B mRNA expression
      through direct binding to Cdc25B promoter and mediated its transcriptional
      attenuation through NF-YB and p300 transcriptinal factors. In summary, we found
      that transcriptional repression mediated by IER5 regulates Cdc25B expression
      levels via the release of NF-YB and p300 in AML-derived ALDH(hi)/CD34(+) cells,
      resulting in inhibition of AML progenitor cell proliferation through modulation
      of cell cycle. Thus, the induction of IER5 expression represents an attractive
      target for AML therapy.

PMID- 22132195
TI  - Programmatic evaluation of a combined antigen and antibody test for rapid HIV
      diagnosis in a community and sexual health clinic screening programme.
AB  - BACKGROUND: A substantial proportion of HIV-infected individuals in the UK are
      unaware of their status and late presentations continue, especially in low
      prevalence areas. Fourth generation antigen/antibody rapid test kits could
      facilitate earlier diagnosis of HIV in non-clinical settings but lack data on
      performance under programmatic conditions. METHODS AND FINDINGS: We evaluated the
      performance of Determine HIV-1/2 Ag/Ab Combo Test (Determine Combo), a rapid test
      with indicators for both HIV antibodies and p24 antigen, in participants
      recruited from community outreach and hospital-based sexual health clinics. HIV
      infection was confirmed using laboratory enzyme-linked immunosorbent assay (EIA),
      Line Immuno Assay (LIA) and quantitative polymerase chain reaction (PCR). In
      total, 953 people underwent HIV testing. HIV antibody (Ab) prevalence was 1.8%
      (17/953). Four false positive rapid tests were identified: two antibody and two
      p24 antigen (Ag) reactions. Of participants diagnosed as HIV Ab positive, 2/17
      (12%) were recent seroconverters based on clinical history and HIV antibody
      avidity test results. However, none of these were detected by the p24 antigen
      component of the rapid test kit. There were no other true positive p24 Ag tests.
      CONCLUSION: These data lend support to an increasing body of evidence suggesting
      that 4th generation rapid HIV tests have little additional benefit over 3rd
      generation HIV kits for routine screening in low prevalence settings and have
      high rates of false positives. In order to optimally combine community-based case
      finding among hard-to-reach groups with reliable and early diagnosis 3rd
      generation kits should be primarily used with laboratory testing of individuals
      thought to be at risk of acute HIV infection. A more reliable point of care
      diagnostic is required for the accurate detection of acute HIV infection under
      programmatic conditions.

PMID- 22132194
TI  - HIV gp120 binds to mannose receptor on vaginal epithelial cells and induces
      production of matrix metalloproteinases.
AB  - BACKGROUND: During sexual transmission of HIV in women, the virus breaches the
      multi-layered CD4 negative stratified squamous epithelial barrier of the vagina,
      to infect the sub-epithelial CD4 positive immune cells. However the mechanisms by
      which HIV gains entry into the sub-epithelial zone is hitherto unknown. We have
      previously reported human mannose receptor (hMR) as a CD4 independent receptor
      playing a role in HIV transmission on human spermatozoa. The current study was
      undertaken to investigate the expression of hMR in vaginal epithelial cells, its
      HIV gp120 binding potential, affinity constants and the induction of matrix
      metalloproteinases (MMPs) downstream of HIV gp120 binding to hMR. PRINCIPAL
      FINDINGS: Human vaginal epithelial cells and the immortalized vaginal epithelial
      cell line Vk2/E6E7 were used in this study. hMR mRNA and protein were expressed
      in vaginal epithelial cells and cell line, with a molecular weight of 155 kDa.
      HIV gp120 bound to vaginal proteins with high affinity, (Kd = 1.2+/-0.2 nM for
      vaginal cells, 1.4+/-0.2 nM for cell line) and the hMR antagonist mannan dose
      dependently inhibited this binding. Both HIV gp120 binding and hMR exhibited
      identical patterns of localization in the epithelial cells by immunofluorescence.
      HIV gp120 bound to immunopurified hMR and affinity constants were 2.9+/-0.4 nM
      and 3.2+/-0.6 nM for vaginal cells and Vk2/E6E7 cell line respectively. HIV gp120
      induced an increase in MMP-9 mRNA expression and activity by zymography, which
      could be inhibited by an anti-hMR antibody. CONCLUSION: hMR expressed by vaginal
      epithelial cells has high affinity for HIV gp120 and this binding induces
      production of MMPs. We propose that the induction of MMPs in response to HIV
      gp120 may lead to degradation of tight junction proteins and the extracellular
      matrix proteins in the vaginal epithelium and basement membrane, leading to
      weakening of the epithelial barrier; thereby facilitating transport of HIV across
      the vaginal epithelium.

PMID- 22132196
TI  - Mobility, balance and falls in persons with multiple sclerosis.
AB  - BACKGROUND: There is a lack of information concerning the relation between
      objective measures of gait and balance and fall history in persons with MS
      (PwMS). This investigation assessed the relation between demographic, clinical,
      mobility and balance metrics and falls history in persons with multiple sclerosis
      (MS). METHODS: 52 ambulatory persons with MS (PwMS) participated in the
      investigation. All persons provided demographic information including fall
      history over the last 12 months. Disease status was assessed with Expanded
      Disability Status Scale (EDSS). Walking speed, coordination, endurance and
      postural control were quantified with a multidimensional mobility battery.
      RESULTS: Over 51% of the participants fell in the previous year with 79% of these
      people being suffering recurrent falls. Overall, fallers were older, had a
      greater prevalence of assistive devices use, worse disability, decreased walking
      endurance, and greater postural sway velocity with eyes closed compared to non
      fallers. Additionally, fallers had greater impairment in cerebellar, sensory,
      pyramidal, and bladder/bowel subscales of the EDSS. CONCLUSIONS: The current
      observations suggest that PwMS who are older, more disabled, utilize an assistive
      device, have decreased walking coordination and endurance and have diminished
      balance have fallen in the previous year. This suggests that individuals who meet
      these criteria need to be carefully monitored for future falls. Future research
      is needed to determine a prospective model of falls specific to PwMS.
      Additionally, the utility of interventions aimed at reducing falls and fall risk
      in PwMS needs to be established.

PMID- 22132197
TI  - Lymphangiogenesis is required for pancreatic islet inflammation and diabetes.
AB  - Lymphangiogenesis is a common phenomenon observed during inflammation and
      engraftment of transplants, but its precise role in the immune response and
      underlying mechanisms of regulation remain poorly defined. Here we showed that in
      response to injury and autoimmunity, lymphangiogenesis occurred around islets and
      played a key role in the islet inflammation in mice. Vascular endothelial growth
      factors receptor 3 (VEGFR3) is specifically involved in lymphangiogenesis, and
      blockade of VEGFR3 potently inhibited lymphangiogenesis in both islets and the
      draining LN during multiple low-dose streptozotocin (MLDS) induced autoimmune
      insulitis, which resulted in less T cell infiltration, preservation of islets and
      prevention of the onset of diabetes. In addition to their well-known conduit
      function, lymphatic endothelial cells (LEC) also produced chemokines in response
      to inflammation. These LEC attracted two distinct CX3CR1(hi) and LYVE-1(+)
      macrophage subsets to the inflamed islets and CX3CR1(hi) cells were influenced by
      LEC to differentiate into LYVE-1(+) cells closely associated with lymphatic
      vessels. These observations indicate a linkage among lymphangiogenesis and
      myeloid cell inflammation during insulitis. Thus, inhibition of lymphangiogenesis
      holds potential for treating insulitis and autoimmune diabetes.

PMID- 22132198
TI  - Non-invasive imaging of cysteine cathepsin activity in solid tumors using a 64Cu
      labeled activity-based probe.
AB  - The papain family of cysteine cathepsins are actively involved in multiple stages
      of tumorigenesis. Because elevated cathepsin activity can be found in many types
      of human cancers, they are promising biomarkers that can be used to target
      radiological contrast agents for tumor detection. However, currently there are no
      radiological imaging agents available for these important molecular targets. We
      report here the development of positron emission tomography (PET) radionuclide
      labeled probes that target the cysteine cathepsins by formation of an enzyme
      activity-dependent bond with the active site cysteine. These probes contain an
      acyloxymethyl ketone (AOMK) functional group that irreversibly labels the active
      site cysteine of papain family proteases attached to a 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tag for labeling with
      (64)Cu for PET imaging studies. We performed biodistribution and microPET imaging
      studies in nude mice bearing subcutaneous tumors expressing various levels of
      cysteine cathepsin activity and found that the extent of probe uptake by tumors
      correlated with overall protease activity as measured by biochemical methods.
      Furthermore, probe signals could be reduced by pre-treatment with a general
      cathepsin inhibitor. We also found that inclusion of a Cy5 tag on the probe
      increased tumor uptake relative to probes lacking this fluorogenic dye. Overall,
      these results demonstrate that small molecule activity-based probes carrying
      radio-tracers can be used to image protease activity in living subjects.

PMID- 22132199
TI  - Polymorphisms in genes involved in the NF-kappaB signalling pathway are
      associated with bone mineral density, geometry and turnover in men.
AB  - INTRODUCTION: In this study, we aimed to investigate the association between
      single nucleotide polymorphisms (SNPs) within two genes involved in the NF-kappaB
      cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different
      skeletal sites, radial geometric parameters and bone turnover. METHODS: Ten
      GPR177 SNPs previously associated with BMD with genome-wide significance and
      twelve tag SNPs (r(2)>=0.8) within MAP3K14 (+/-10 kb) were genotyped in 2359 men
      aged 40-79 years recruited from 8 centres for participation in the European Male
      Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the
      serum and quantitative ultrasound (QUS) at the calcaneus were performed in all
      centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and
      peripheral quantitative computed tomography (pQCT), at the distal and midshaft
      radius, were performed in a subsample (2 centres). Linear regression was used to
      test for association between the SNPs and bone measures under an additive genetic
      model adjusting for study centre. RESULTS: We validated the associations between
      SNPs in GPR177 and BMD(a) previously reported and also observed evidence of
      pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated
      with increased total hip and LS BMD(a), increased total and cortical vBMD at the
      radius and increased cortical area, thickness and stress strain index. We also
      found evidence of association with BMD(a), vBMD, geometric parameters and CTX-I
      for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with
      calcaneal estimated BMD measured by QUS. CONCLUSION: Our findings suggest that
      SNPs in GPR177 and MAP3K14 involved in the NF-kappaB signalling pathway influence
      bone mineral density, geometry and turnover in a population-based cohort of
      middle aged and elderly men. This adds to the understanding of the role of
      genetic variation in this pathway in determining bone health.

PMID- 22132200
TI  - The MDT-15 subunit of mediator interacts with dietary restriction to modulate
      longevity and fluoranthene toxicity in Caenorhabditis elegans.
AB  - Dietary restriction (DR), the limitation of calorie intake while maintaining
      proper nutrition, has been found to extend life span and delay the onset of age
      associated disease in a wide range of species. Previous studies have suggested
      that DR can reduce the lethality of environmental toxins. To further examine the
      role of DR in toxin response, we measured life spans of the nematode
      Caenorhabditis elegans treated with the mutagenic polyaromatic hydrocarbon,
      fluoranthene (FLA). FLA is a direct byproduct of combustion, and is one of U.S.
      Environmental Protection Agency's sixteen priority environmental toxins.
      Treatment with 5 ug/ml FLA shortened the life spans of ad libitum fed nematodes,
      and DR resulted in increased sensitivity to FLA. To determine the role of
      detoxifying enzymes in the toxicity of FLA, we tested nematodes with mutations in
      the gene encoding the MDT-15 subunit of mediator, a transcriptional coactivator
      that regulates genes involved in fatty acid metabolism and detoxification.
      Mutation of mdt-15 increased the life span of FLA treated animals compared to
      wild-type animals with no difference observed between DR and ad libitum fed mdt
      15 animals. We also examined mutants with altered insulin-IGF-1-like signaling
      (IIS), which is known to modulate life span and stress resistance in C. elegans
      independently of DR. Mutation of the genes coding for the insulin-like receptor
      DAF-2 or the FOXO-family transcription factor DAF16 did not alter the animals'
      susceptibility to FLA compared to wild type. Taken together, our results suggest
      that certain compounds have increased toxicity when combined with a DR regimen
      through increased metabolic activation. This increased metabolic activation
      appears to be mediated through the MDT-15 transcription factor and is independent
      of the IIS pathway.

PMID- 22132201
TI  - The anticancer plant triterpenoid, avicin D, regulates glucocorticoid receptor
      signaling: implications for cellular metabolism.
AB  - Avicins, a family of apoptotic triterpene electrophiles, are known to regulate
      cellular metabolism and energy homeostasis, by targeting the mitochondria. Having
      evolved from "ancient hopanoids," avicins bear a structural resemblance with
      glucocorticoids (GCs), which are the endogenous regulators of metabolism and
      energy balance. These structural and functional similarities prompted us to
      compare the mode of action of avicin D with dexamethasone (Dex), a prototypical
      GC. Using cold competition assay, we show that Avicin D competes with Dex for
      binding to the GC receptor (GR), leading to its nuclear translocation. In
      contrast to Dex, avicin-induced nuclear translocation of GR does not result in
      transcriptional activation of GC-dependent genes. Instead we observe a decrease
      in the expression of GC-dependent metabolic proteins such as PEPCK and FASN.
      However, like Dex, avicin D treatment does induce a transrepressive effect on the
      pro-inflammatory transcription factor NF-kappaB. While avicin's ability to
      inhibit NF-kappaB and its downstream targets appear to be GR-dependent, its pro
      apoptotic effects were independent of GR expression. Using various deletion
      mutants of GR, we demonstrate the requirement of both the DNA and ligand binding
      domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin
      GR interaction revealed that avicin molecule binds only to the antagonist
      confirmation of GR. These findings suggest that avicin D has properties of being
      a selective GR modulator that separates transactivation from transrepression.
      Since the gene-activating properties of GR are mainly linked to its metabolic
      effects, and the negative interference with the activity of transcription factors
      to its anti-inflammatory and immune suppressive effects, the identification of
      such a dissociated GR ligand could have great potential for therapeutic use.

PMID- 22132202
TI  - Health behaviors, care needs and attitudes towards self-prescription: a cross
      sectional survey among Dutch medical students.
AB  - PURPOSE: There is a growing awareness of the potent ways in which the wellbeing
      of physicians impacts the health of their patients. The purpose of this study was
      to investigate the health behaviors, care needs and attitudes towards self
      prescription of Dutch medical students, and any differences between junior
      preclinical and senior clinically active students. METHODS: All students (n =
      2695) of a major Dutch medical school were invited for an online survey. Physical
      activity, eating habits, alcohol consumption, smoking, Body Mass Index, substance
      use and amount of sleep per night were inquired, as well as their need for
      different forms of care and their attitude towards self-prescription. RESULTS:
      Data of 902 students were used. Physical activity levels (90% sufficient) and
      smoking prevalence (94% non-smokers) were satisfying. Healthy eating habits (51%
      insufficient) and alcohol consumption (46% excessive) were worrying. Body Mass
      Indexes were acceptable (20% unhealthy). We found no significant differences in
      health behaviors between preclinical and clinically active students. Care needs
      were significantly lower among clinically active students. (p<0.05) Student
      acceptance of self-prescription was significantly higher among clinically active
      students. (p<0.001) CONCLUSIONS: Unhealthy behaviors are prevalent among medical
      students, but are no more prevalent during the clinical study phase. The need for
      specific forms of care appears lower with study progression. This could be
      worrying as the acceptance of self-care and self-prescription is higher among
      senior clinical students. Medical faculties need to address students' unhealthy
      behaviors and meet their care needs for the benefit of both the future physicians
      as well as their patients.

PMID- 22132203
TI  - Divergent biochemical fractionation, not convergent temperature, explains
      cellulose oxygen isotope enrichment across latitudes.
AB  - Recent findings based on the oxygen isotope ratios of tree trunk cellulose
      indicate that the temperature of biomass production in biomes ranging from boreal
      to subtropical forests converge to an average leaf temperature of 21.4 degrees C.
      The above conclusion has been drawn under the assumption that biochemically
      related isotopic fractionations during cellulose synthesis are not affected by
      temperature. Here we test the above assumption by heterotrophically generating
      cellulose at different temperatures and measuring the proportion of carbohydrate
      oxygen that exchange with water during cellulose synthesis and the average
      biochemical fractionation associated with this exchange. We observed no variation
      in the proportion of oxygen that exchange with different temperatures, which
      averaged 0.42 as it has been observed in other studies. On the other hand, the
      biochemical oxygen isotope fractionation during cellulose synthesis is affected
      by temperature and can be described by a 2(nd) order polynomial equation. The
      biochemical fractionation changes little between temperatures of 20 and 30
      degrees C averaging 260/00 but increases at lower temperatures to values of
      310/00. This temperature sensitive biochemical fractionation explains the pattern
      of cellulose oxygen isotope ratios of aquatic plants encompassing several
      latitudes. The observed temperature sensitive biochemical fractionation also
      indicates that divergent biochemical fractionation and not convergent leaf
      temperature explains the increase in oxygen isotope enrichment of cellulose
      across several biomes.

PMID- 22132204
TI  - Subclinical epileptiform process in patients with unipolar depression and its
      indirect psychophysiological manifestations.
AB  - BACKGROUND: According to recent clinical findings epileptiform activity in
      temporolimbic structures may cause depressive and other psychiatric symptoms that
      may occur independently of any seizure in patient's history. In addition in these
      patients subclinical seizure-like activity with indirect clinical manifestations
      likely may occur in a form of various forms of cognitive, affective, memory,
      sensory, behavioral and somatic symptoms (the so-called complex partial seizure
      like symptoms). A typical characteristic of epileptiform changes is increased
      neural synchrony related to spreading of epileptiform activity between
      hemispheres even in subclinical conditions i.e. without seizures. These findings
      suggest a hypothesis that measures reflecting a level of synchronization and
      information transfer between hemispheres could reflect spreading of epileptiform
      activity and might be related to complex partial seizure-like symptoms. METHODS
      AND FINDINGS: Suitable data for such analysis may provide various physiological
      signals reflecting brain laterality, as for example bilateral electrodermal
      activity (EDA) that is closely related to limbic modulation influences. With this
      purpose we have performed measurement and analysis of bilateral EDA and compared
      the results with psychometric measures of complex partial seizure-like symptoms,
      depression and actually experienced stress in 44 patients with unipolar
      depression and 35 healthy controls. The results in unipolar depressive patients
      show that during rest conditions the patients with higher level of complex
      partial seizure like symptoms (CPSI) display increased level of EDA
      transinformation (PTI) calculated between left and right EDA records (Spearman
      correlation between CPSI and PTI is r = 0.43, p = 0.004). CONCLUSIONS: The result
      may present potentially useful clinical finding suggesting that increased EDA
      transinformation (PTI) could indirectly indicate increased neural synchrony as a
      possible indicator of epileptiform activity in unipolar depressive patients
      treated by serotoninergic antidepresants.

PMID- 22132205
TI  - Persistence of the 2009 pandemic influenza A (H1N1) virus in water and on non
      porous surface.
AB  - Knowledge of influenza A virus survival in different environmental conditions is
      a key element for the implementation of hygiene and personal protection measures
      by health authorities. As it is dependent on virus isolates even within the same
      subtype, we studied the survival of the 2009 H1N1 pandemic (H1N1pdm) virus in
      water and on non-porous surface. The H1N1pdm virus was subjected to various
      environmental parameters over time and tested for infectivity. In water, at low
      and medium salinity levels and 4 degrees C, virus survived at least 200 days.
      Increasing temperature and salinity had a strong negative effect on the survival
      of the virus which remained infectious no more than 1 day at 35 degrees C and 270
      parts per thousand (ppt) of salt. Based on modeled data, the H1N1pdm virus
      retained its infectivity on smooth non-porous surface for at least 7 days at 35
      degrees C and up to 66 days at 4 degrees C. The H1N1pdm virus has thus the
      ability to persist in water and on glass surface for extended periods of time,
      even at 35 degrees C. Additional experiments suggest that external viral
      structures in direct contact with the environment are mostly involved in loss of
      virus infectivity.

PMID- 22132206
TI  - Impaired structural connectivity of socio-emotional circuits in autism spectrum
      disorders: a diffusion tensor imaging study.
AB  - BACKGROUND: Abnormal white matter development may disrupt integration within
      neural circuits, causing particular impairments in higher-order behaviours. In
      autism spectrum disorders (ASDs), white matter alterations may contribute to
      characteristic deficits in complex socio-emotional and communication domains.
      Here, we used diffusion tensor imaging (DTI) and tract based spatial statistics
      (TBSS) to evaluate white matter microstructure in ASD. METHODS/PRINCIPAL
      FINDINGS: DTI scans were acquired for 19 children and adolescents with ASD (~8-18
      years; mean 12.4+/-3.1) and 16 age and IQ matched controls (~8-18 years; mean
      12.3+/-3.6) on a 3T MRI system. DTI values for fractional anisotropy, mean
      diffusivity, radial diffusivity and axial diffusivity, were measured. Age by
      group interactions for global and voxel-wise white matter indices were examined.
      Voxel-wise analyses comparing ASD with controls in: (i) the full cohort (ii),
      children only (<=12 yrs.), and (iii) adolescents only (>12 yrs.) were performed,
      followed by tract-specific comparisons. Significant age-by-group interactions on
      global DTI indices were found for all three diffusivity measures, but not for
      fractional anisotropy. Voxel-wise analyses revealed prominent diffusion measure
      differences in ASD children but not adolescents, when compared to healthy
      controls. Widespread increases in mean and radial diffusivity in ASD children
      were prominent in frontal white matter voxels. Follow-up tract-specific analyses
      highlighted disruption to pathways integrating frontal, temporal, and occipital
      structures involved in socio-emotional processing. CONCLUSIONS/SIGNIFICANCE: Our
      findings highlight disruption of neural circuitry in ASD, particularly in those
      white matter tracts that integrate the complex socio-emotional processing that is
      impaired in this disorder.

PMID- 22132207
TI  - The nature of the dietary protein impacts the tissue-to-diet 15N discrimination
      factors in laboratory rats.
AB  - Due to the existence of isotope effects on some metabolic pathways of amino acid
      and protein metabolism, animal tissues are (15)N-enriched relative to their
      dietary nitrogen sources and this (15)N enrichment varies among different tissues
      and metabolic pools. The magnitude of the tissue-to-diet discrimination
      (Delta(15)N) has also been shown to depend on dietary factors. Since dietary
      protein sources affect amino acid and protein metabolism, we hypothesized that
      they would impact this discrimination factor, with selective effects at the
      tissue level. To test this hypothesis, we investigated in rats the influence of a
      milk or soy protein-based diet on Delta(15)N in various nitrogen fractions (urea,
      protein and non-protein fractions) of blood and tissues, focusing on visceral
      tissues. Regardless of the diet, the different protein fractions of blood and
      tissues were generally (15)N-enriched relative to their non-protein fraction and
      to the diet (Delta(15)N>0), with large variations in the Delta(15)N between
      tissue proteins. Delta(15)N values were markedly lower in tissue proteins of rats
      fed milk proteins compared to those fed soy proteins, in all sampled tissues
      except in the intestine, and the amplitude of Delta(15)N differences between
      diets differed between tissues. Both between-tissue and between-diet Delta(15)N
      differences are probably related to modulations of the relative orientation of
      dietary and endogenous amino acids in the different metabolic pathways. More
      specifically, the smaller Delta(15)N values observed in tissue proteins with milk
      than soy dietary protein may be due to a slightly more direct channeling of
      dietary amino acids for tissue protein renewal and to a lower recycling of amino
      acids through fractionating pathways. In conclusion, the present data indicate
      that natural Delta(15)N of tissue are sensitive markers of the specific subtle
      regional modifications of the protein and amino acid metabolism induced by the
      protein dietary source.

PMID- 22132208
TI  - Transcriptional downregulation of rice rpL32 gene under abiotic stress is
      associated with removal of transcription factors within the promoter region.
AB  - BACKGROUND: The regulation of ribosomal proteins in plants under stress
      conditions has not been well studied. Although a few reports have shown stress
      specific post-transcriptional and translational mechanisms involved in
      downregulation of ribosomal proteins yet stress-responsive transcriptional
      regulation of ribosomal proteins is largely unknown in plants.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present work, transcriptional regulation
      of genes encoding rice 60S ribosomal protein L32 (rpL32) in response to salt
      stress has been studied. Northern and RT-PCR analyses showed a significant
      downregulation of rpL32 transcripts under abiotic stress conditions in rice. Of
      the four rpL32 genes in rice genome, the gene on chromosome 8 (rpL32_8.1) showed
      a higher degree of stress-responsive downregulation in salt sensitive rice
      variety than in tolerant one and its expression reverted to its original level
      upon withdrawal of stress. The nuclear run-on and promoter:reporter assays
      revealed that the downregulation of this gene is transcriptional and originates
      within the promoter region. Using in vivo footprinting and electrophoretic
      mobility shift assay (EMSA), cis-elements in the promoter of rpL32_8.1 showing
      reduced binding to proteins in shoots of salt stressed rice seedlings were
      identified. CONCLUSIONS: The present work is one of the few reports on study of
      stress downregulated genes. The data revealed that rpL32 gene is
      transcriptionally downregulated under abiotic stress in rice and that this
      transcriptional downregulation is associated with the removal of transcription
      factors from specific promoter elements.

PMID- 22132209
TI  - Biochemical trade-offs: evidence for ecologically linked secondary metabolism of
      the sponge Oscarella balibaloi.
AB  - Secondary metabolite production is assumed to be costly and therefore the
      resource allocation to their production should be optimized with respect to
      primary biological functions such as growth or reproduction. Sponges are known to
      produce a great diversity of secondary metabolites with powerful biological
      activities that may explain their domination in some hard substrate communities
      both in terms of diversity and biomass. Oscarella balibaloi (Homoscleromorpha) is
      a recently described, highly dynamic species, which often overgrows other sessile
      marine invertebrates. Bioactivity measurements (standardized Microtox assay) and
      metabolic fingerprints were used as indicators of the baseline variations of the
      O. balibaloi secondary metabolism, and related to the sponge reproductive effort
      over two years. The bioactivity showed a significant seasonal variation with the
      lowest values at the end of spring and in early summer followed by the highest
      bioactivity in the late summer and autumn. An effect of the seawater temperature
      was detected, with a significantly higher bioactivity in warm conditions. There
      was also a tendency of a higher bioactivity when O. balibaloi was found
      overgrowing other sponge species. Metabolic fingerprints revealed the existence
      of three principal metabolic phenotypes: phenotype 1 exhibited by a majority of
      low bioactive, female individuals, whereas phenotypes 2 and 3 correspond to a
      majority of highly bioactive, non-reproductive individuals. The bioactivity was
      negatively correlated to the reproductive effort, minimal bioactivities
      coinciding with the period of embryogenesis and larval development. Our results
      fit the Optimal Defense Theory with an investment in the reproduction mainly
      shaping the secondary metabolism variability, and a less pronounced influence of
      other biotic (species interaction) and abiotic (temperature) factors.

PMID- 22132210
TI  - Risk adjustment for inter-hospital comparison of caesarean delivery rates in low
      risk deliveries.
AB  - BACKGROUND: Caesarean delivery (CD) rates have been frequently used as quality
      measures for maternity service comparisons. More recently, primary CD rates (CD
      in women without previous CD) or CD rates within selected categories such as
      nulliparous, term, cephalic singleton deliveries (NTCS) have been used. The
      objective of this study is to determine the extent to which risk adjustment for
      clinical and socio-demographic variables is needed for inter-hospital comparisons
      of CD rates in women without previous CD and in NTCS deliveries. METHODS:
      Hospital discharge records of women who delivered in Emilia-Romagna Region
      (Italy) from January, 2007 to June 2009 and in Tuscany Region for year 2009 were
      linked with birth certificates. Adjusted RRs of CD in women without a previous
      Caesarean and NTCS were estimated using Poisson regression. Percentage
      differences in RR before and after adjustment were calculated and hospital
      rankings, based on crude and adjusted RRs, were examined. RESULTS: Adjusted RR
      differed substantially from crude RR in women without a previous Caesarean and
      only marginally in NTCS group. Hospital ranking was markedly affected by
      adjustment in women without a previous CD, but less in NTCS. CONCLUSION: Risk
      adjustment is warranted for inter-hospital comparisons of primary CD rates but
      not for NTCS CD rates. Crude NTCS CD rates are a reliable estimate of adjusted
      NTCS CD.

PMID- 22132211
TI  - The ubiquity of intraguild predation among predatory arthropods.
AB  - Intraguild predation (IGP) occurs when one predator species attacks another
      predator species with which it competes for a shared prey species. Despite the
      apparent omnipresence of intraguild interactions in natural and managed
      ecosystems, very few studies have quantified rates of IGP in various taxa under
      field conditions. We used molecular analyses of gut contents to assess the nature
      and incidence of IGP among four species of coccinellid predators in soybean
      fields. Over half of the 368 predator individuals collected in soybean contained
      the DNA of other coccinellid species indicating that IGP was very common at our
      field site. Furthermore, 13.2% of the sampled individuals contained two and even
      three other coccinellid species in their gut. The interaction was reciprocal, as
      each of the four coccinellid species has the capacity to feed on the others. To
      our knowledge, this study represents the most convincing field evidence of a high
      prevalence of IGP among predatory arthropods. The finding has important
      implications for conservation biology and biological control.

PMID- 22132212
TI  - Humoral and cell-mediated immunity to pandemic H1N1 influenza in a Canadian
      cohort one year post-pandemic: implications for vaccination.
AB  - We evaluated a cohort of Canadian donors for T cell and antibody responses
      against influenza A/California/7/2009 (pH1N1) at 8-10 months after the 2nd
      pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell
      responses to pH1N1 were detectable in 58% (61/105) of donors. These responses
      were largely due to cross-reactive CD8 T cell epitopes as, for those donors
      tested, similar recall responses were obtained to A/California 2009 and A/PR8
      1934 H1N1 Hviruses. Longitudinal analysis of a single infected individual showed
      only a small and transient increase in neutralizing antibody levels, but a robust
      CD8 T cell response that rose rapidly post symptom onset, peaking at 3 weeks,
      followed by a gradual decline to the baseline levels seen in a seroprevalence
      cohort post-pandemic. The magnitude of the influenza-specific CD8 T cell memory
      response at one year post-pandemic was similar in cases and controls as well as
      in vaccinated and unvaccinated donors, suggesting that any T cell boosting from
      infection was transient. Pandemic H1-specific antibodies were only detectable in
      approximately half of vaccinated donors. However, those who were vaccinated
      within a few months following infection had the highest persisting antibody
      titers, suggesting that vaccination shortly after influenza infection can boost
      or sustain antibody levels. For the most part the circulating influenza-specific
      T cell and serum antibody levels in the population at one year post-pandemic were
      not different between cases and controls, suggesting that natural infection does
      not lead to higher long term T cell and antibody responses in donors with pre
      existing immunity to influenza. However, based on the responses of one
      longitudinal donor, it is possible for a small population of pre-existing cross
      reactive memory CD8 T cells to expand rapidly following infection and this
      response may aid in viral clearance and contribute to a lessening of disease
      severity.

PMID- 22132213
TI  - Insulin receptor-mediated signaling via phospholipase C-gamma regulates growth
      and differentiation in Drosophila.
AB  - Coordination between growth and patterning/differentiation is critical if
      appropriate final organ structure and size is to be achieved. Understanding how
      these two processes are regulated is therefore a fundamental and as yet
      incompletely answered question. Here we show through genetic analysis that the
      phospholipase C-gamma (PLC-gamma) encoded by small wing (sl) acts as such a link
      between growth and patterning/differentiation by modulating some MAPK outputs
      once activated by the insulin pathway; particularly, sl promotes growth and
      suppresses ectopic differentiation in the developing eye and wing, allowing cells
      to attain a normal size and differentiate properly. sl mutants have previously
      been shown to have a combination of both growth and patterning/differentiation
      phenotypes: small wings, ectopic wing veins, and extra R7 photoreceptor cells. We
      show here that PLC-gamma activated by the insulin pathway participates broadly
      and positively during cell growth modulating EGF pathway activity, whereas in
      cell differentiation PLC-gamma activated by the insulin receptor negatively
      regulates the EGF pathway. These roles require different SH2 domains of PLC
      gamma, and act via classic PLC-gamma signaling and EGF ligand processing. By
      means of PLC-gamma, the insulin receptor therefore modulates differentiation as
      well as growth. Overall, our results provide evidence that PLC-gamma acts during
      development at a time when growth ends and differentiation begins, and is
      important for proper coordination of these two processes.

PMID- 22132214
TI  - Metformin represses self-renewal of the human breast carcinoma stem cells via
      inhibition of estrogen receptor-mediated OCT4 expression.
AB  - Metformin, a Type II diabetic treatment drug, which inhibits transcription of
      gluconeogenesis genes, has recently been shown to lower the risk of some diabetes
      related tumors, including breast cancer. Recently, "cancer stem cells" have been
      demonstrated to sustain the growth of tumors and are resistant to therapy. To
      test the hypothesis that metformin might be reducing the risk to breast cancers,
      the human breast carcinoma cell line, MCF-7, grown in 3-dimensional mammospheres
      which represent human breast cancer stem cell population, were treated with
      various known and suspected breast cancer chemicals with and without non
      cytotoxic concentrations of metformin. Using OCT4 expression as a marker for the
      cancer stem cells, the number and size were measured in these cells. Results
      demonstrated that TCDD (100 nM) and bisphenol A (10 uM) increased the number and
      size of the mammospheres, as did estrogen (10 nM E2). By monitoring a cancer stem
      cell marker, OCT4, the stimulation by these chemicals was correlated with the
      increased expression of OCT4. On the other hand, metformin at 1 and 10 mM
      concentration dramatically reduced the size and number of mammospheres. Results
      also demonstrated the metformin reduced the expression of OCT4 in E2 & TCDD
      mammospheres but not in the bisphenol A mammospheres, suggesting different
      mechanisms of action of the bisphenol A on human breast carcinoma cells. In
      addition, these results support the use of 3-dimensional human breast cancer stem
      cells as a means to screen for potential human breast tumor promoters and breast
      chemopreventive and chemotherapeutic agents.

PMID- 22132215
TI  - The role of the novel exopolyphosphatase MT0516 in Mycobacterium tuberculosis
      drug tolerance and persistence.
AB  - Inorganic polyphosphate (poly P) has been postulated to play a regulatory role in
      the transition to bacterial persistence. In bacteria, poly P balance in the cell
      is maintained by the hydrolysis activity of the exopolyphosphatase PPX. However,
      the Mycobacterium tuberculosis PPX has not been characterized previously. Here we
      show that recombinant MT0516 hydrolyzes poly P, and an MT0516-deficient M.
      tuberculosis mutant exhibits elevated intracellular levels of poly P and
      increased expression of the genes mprB, sigE, and rel relative to the isogenic
      wild-type strain, indicating poly P-mediated signaling. Deficiency of MT0516
      resulted in decelerated growth during logarithmic-phase in axenic cultures, and
      tolerance to the cell wall-active drug isoniazid. The MT0516-deficient mutant
      showed a significant survival defect in activated human macrophages and reduced
      persistence in the lungs of guinea pigs. We conclude that exopolyphosphatase is
      required for long-term survival of M. tuberculosis in necrotic lung lesions.

PMID- 22132216
TI  - A RCT of a transdiagnostic internet-delivered treatment for three anxiety
      disorders: examination of support roles and disorder-specific outcomes.
AB  - BACKGROUND: Anxiety disorders share common vulnerabilities and symptoms. Disorder
      specific treatment is efficacious, but few access evidence-based care.
      Administering transdiagnostic cognitive-behavioral therapy via the internet
      (iCBT) may increase access to evidence-based treatment, with a recent randomized
      controlled trial (RCT) providing preliminary support for this approach. This
      study extends those findings and aims to answer three questions: Is a
      transdiagnostic iCBT program for anxiety disorders efficacious and acceptable?
      Does it result in change for specific disorders? Can good clinical outcomes be
      obtained when guidance is provided via a Coach rather than a Clinician? METHOD:
      RCT (N = 131) comparing three groups: Clinician-supported (CL) vs. Coach
      supported (CO) vs. waitlist control (Control). Individuals met DSM-IV criteria
      for a principal diagnosis of generalized anxiety disorder (GAD), social phobia
      (SP) or panic disorder with or without agoraphobia (Pan/Ag). Treatment consisted
      of an 8-lesson/10 week iCBT program with weekly contact from a Clinician or
      Coach, and follow-up at 3-months post-treatment. RESULTS: Outcomes for the pooled
      treatment groups (CL+CO) were superior to the Control group on measures of
      anxiety, depression and disability, were associated with medium to large effect
      sizes (Cohen's d = .76-1.44) (response rate = 89-100%), and were maintained at
      follow-up. Significant reductions were found on disorder-specific outcomes for
      each of the target diagnoses, and were associated with large effect sizes. CO
      participants achieved similar outcomes to CL participants at post-treatment, yet
      had significantly lower symptom severity scores on general anxiety, panic
      disorder, depression and disability at follow-up (d = .45-.46). Seventy-four
      percent of CO and 76% of CL participants completed the program. Less than 70
      minutes of Clinician or Coach time was required per participant during the
      program. DISCUSSION: This transdiagnostic iCBT course for anxiety appears to be
      efficacious, associated with significant change for three target disorders, and
      is efficacious when guided by either a Clinician or Coach. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry ACTRN12610000242022.

PMID- 22132217
TI  - Magnetoencephalography study of right parietal lobe dysfunction of the evoked
      mirror neuron system in antipsychotic-free schizophrenia.
AB  - INTRODUCTION: Patients with schizophrenia commonly exhibit deficits of non-verbal
      communication in social contexts, which may be related to cognitive dysfunction
      that impairs recognition of biological motion. Although perception of biological
      motion is known to be mediated by the mirror neuron system, there have been few
      empirical studies of this system in patients with schizophrenia. METHODS: Using
      magnetoencephalography, we examined whether antipsychotic-free schizophrenia
      patients displayed mirror neuron system dysfunction during observation of
      biological motion (jaw movement of another individual). RESULTS: Compared with
      normal controls, the patients with schizophrenia had fewer components of both the
      waveform and equivalent current dipole, suggesting aberrant brain activity
      resulting from dysfunction of the right inferior parietal cortex. They also
      lacked the changes of alpha band and gamma band oscillation seen in normal
      controls, and had weaker phase-locking factors and gamma-synchronization
      predominantly in right parietal cortex. CONCLUSIONS: Our findings demonstrate
      that untreated patients with schizophrenia exhibit aberrant mirror neuron system
      function based on the right inferior parietal cortex, which is characterized by
      dysfunction of gamma-synchronization in the right parietal lobe during
      observation of biological motion.

PMID- 22132218
TI  - Comparing the bacterial diversity of acute and chronic dental root canal
      infections.
AB  - This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument
      to compare the microbiota of dental root canal infections associated with acute
      (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples
      from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene
      sequences that were taxonomically classified into 916 bacterial species-level
      operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and
      13 phyla. The most abundant phyla in acute infections were Firmicutes (52%),
      Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the
      dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%).
      Members of Fusobacteria were much more prevalent in acute (89%) than in chronic
      cases (50%). The most abundant/prevalent genera in acute infections were
      Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute
      infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3%
      divergence were shared by acute and chronic infections. Diversity and richness
      estimators revealed that acute infections were significantly more diverse than
      chronic infections. Although a high interindividual variation in bacterial
      communities was observed, many samples tended to group together according to the
      type of infection (acute or chronic). This study is one of the most comprehensive
      in-deep comparisons of the microbiota associated with acute and chronic dental
      root canal infections and highlights the role of diverse polymicrobial
      communities as the unit of pathogenicity in acute infections. The overall
      diversity of endodontic infections as revealed by the pyrosequencing technique
      was much higher than previously reported for endodontic infections.

PMID- 22132219
TI  - Competitive performance of transgenic wheat resistant to powdery mildew.
AB  - Genetically modified (GM) plants offer an ideal model system to study the
      influence of single genes that confer constitutive resistance to pathogens on the
      ecological behaviour of plants. We used phytometers to study competitive
      interactions between GM lines of spring wheat Triticum aestivum carrying such
      genes and control lines. We hypothesized that competitive performance of GM lines
      would be reduced due to enhanced transgene expression under pathogen levels
      typically encountered in the field. The transgenes pm3b from wheat (resistance
      against powdery mildew Blumeria graminis) or chitinase and glucanase genes from
      barley (resistance against fungi in general) were introduced with the ubiquitin
      promoter from maize (pm3b and chitinase genes) or the actin promoter from rice
      (glucanase gene). Phytometers of 15 transgenic and non-transgenic wheat lines
      were transplanted as seedlings into plots sown with the same 15 lines as
      competitive environments and subject to two soil nutrient levels. Pm3b lines had
      reduced mildew incidence compared with control lines. Chitinase and
      chitinase/glucanase lines showed the same high resistance to mildew as their
      control in low-nutrient treatment and slightly lower mildew rates than the
      control in high-nutrient environment. Pm3b lines were weaker competitors than
      control lines. This resulted in reduced yield and seed number. The Pm3b line with
      the highest transgene expression had 53.2% lower yield than the control whereas
      the Pm3b line which segregated in resistance and had higher mildew rates showed
      only minor costs under competition. The line expressing both chitinase and
      glucanase genes also showed reduced yield and seed number under competition
      compared with its control. Our results suggest that single transgenes conferring
      constitutive resistance to pathogens can have ecological costs and can weaken
      plant competitiveness even in the presence of the pathogen. The magnitude of
      these costs appears related to the degree of expression of the transgenes.

PMID- 22132220
TI  - Mutations in the catalytic loop HRD motif alter the activity and function of
      Drosophila Src64.
AB  - The catalytic loop HRD motif is found in most protein kinases and these amino
      acids are predicted to perform functions in catalysis, transition to, and
      stabilization of the active conformation of the kinase domain. We have identified
      mutations in a Drosophila src gene, src64, that alter the three HRD amino acids.
      We have analyzed the mutants for both biochemical activity and biological
      function during development. Mutation of the aspartate to asparagine eliminates
      biological function in cytoskeletal processes and severely reduces fertility,
      supporting the amino acid's critical role in enzymatic activity. The arginine to
      cysteine mutation has little to no effect on kinase activity or cytoskeletal
      reorganization, suggesting that the HRD arginine may not be critical for
      coordinating phosphotyrosine in the active conformation. The histidine to leucine
      mutant retains some kinase activity and biological function, suggesting that this
      amino acid may have a biochemical function in the active kinase that is
      independent of its side chain hydrogen bonding interactions in the active site.
      We also describe the phenotypic effects of other mutations in the SH2 and
      tyrosine kinase domains of src64, and we compare them to the phenotypic effects
      of the src64 null allele.

PMID- 22132221
TI  - Aberrant regulation of HDAC2 mediates proliferation of hepatocellular carcinoma
      cells by deregulating expression of G1/S cell cycle proteins.
AB  - Histone deacetylase 2 (HDAC2) is crucial for embryonic development, affects
      cytokine signaling relevant for immune responses and is often significantly
      overexpressed in solid tumors; but little is known about its role in human
      hepatocellular carcinoma (HCC). In this study, we showed that targeted-disruption
      of HDAC2 resulted in reduction of both tumor cell growth and de novo DNA
      synthesis in Hep3B cells. We then demonstrated that HDAC2 regulated cell cycle
      and that disruption of HDAC2 caused G1/S arrest in cell cycle. In G1/S
      transition, targeted-disruption of HDAC2 selectively induced the expression of
      p16(INK4A) and p21(WAF1/Cip1), and simultaneously suppressed the expression of
      cyclin D1, CDK4 and CDK2. Consequently, HDAC2 inhibition led to the down
      regulation of E2F/DP1 target genes through a reduction in phosphorylation status
      of pRb protein. In addition, sustained suppression of HDAC2 attenuated in vitro
      colony formation and in vivo tumor growth in a mouse xenograft model. Further, we
      found that HDAC2 suppresses p21(WAF1/Cip1) transcriptional activity via Sp1
      binding site enriched proximal region of p21(WAF1/Cip1) promoter. In conclusion,
      we suggest that the aberrant regulation of HDAC2 may play a pivotal role in the
      development of HCC through its regulation of cell cycle components at the
      transcription level providing HDAC2 as a relevant target in liver cancer therapy.

PMID- 22132222
TI  - beta Subunit M2-M3 loop conformational changes are uncoupled from alpha1 beta
      glycine receptor channel gating: implications for human hereditary hyperekplexia.
AB  - Hereditary hyperekplexia, or startle disease, is a neuromotor disorder caused
      mainly by mutations that either prevent the surface expression of, or modify the
      function of, the human heteromeric alpha1 beta glycine receptor (GlyR) chloride
      channel. There is as yet no explanation as to why hyperekplexia mutations that
      modify channel function are almost exclusively located in the alpha1 to the
      exclusion of beta subunit. The majority of these mutations are identified in the
      M2-M3 loop of the alpha1 subunit. Here we demonstrate that alpha1 beta GlyR
      channel function is less sensitive to hyperekplexia-mimicking mutations
      introduced into the M2-M3 loop of the beta than into the alpha1 subunit. This
      suggests that the M2-M3 loop of the alpha subunit dominates the beta subunit in
      gating the alpha1 beta GlyR channel. A further attempt to determine the possible
      mechanism underlying this phenomenon by using the voltage-clamp fluorometry
      technique revealed that agonist-induced conformational changes in the beta
      subunit M2-M3 loop were uncoupled from alpha1 beta GlyR channel gating. This is
      in contrast to the alpha subunit, where the M2-M3 loop conformational changes
      were shown to be directly coupled to alpha1 beta GlyR channel gating. Finally,
      based on analysis of alpha1 beta chimeric receptors, we demonstrate that the
      structural components responsible for this are distributed throughout the beta
      subunit, implying that the beta subunit has evolved without the functional
      constraint of a normal gating pathway within it. Our study provides a possible
      explanation of why hereditary hyperekplexia-causing mutations that modify alpha1
      beta GlyR channel function are almost exclusively located in the alpha1 to the
      exclusion of the beta subunit.

PMID- 22132223
TI  - The glucuronyltransferase GlcAT-P is required for stretch growth of peripheral
      nerves in Drosophila.
AB  - During development, the growth of the animal body is accompanied by a concomitant
      elongation of the peripheral nerves, which requires the elongation of integrated
      nerve fibers and the axons projecting therein. Although this process is of
      fundamental importance to almost all organisms of the animal kingdom, very little
      is known about the mechanisms regulating this process. Here, we describe the
      identification and characterization of novel mutant alleles of GlcAT-P, the
      Drosophila ortholog of the mammalian glucuronyltransferase b3gat1. GlcAT-P
      mutants reveal shorter larval peripheral nerves and an elongated ventral nerve
      cord (VNC). We show that GlcAT-P is expressed in a subset of neurons in the
      central brain hemispheres, in some motoneurons of the ventral nerve cord as well
      as in central and peripheral nerve glia. We demonstrate that in GlcAT-P mutants
      the VNC is under tension of shorter peripheral nerves suggesting that the VNC
      elongates as a consequence of tension imparted by retarded peripheral nerve
      growth during larval development. We also provide evidence that for growth of
      peripheral nerve fibers GlcAT-P is critically required in hemocytes; however,
      glial cells are also important in this process. The glial specific repo gene acts
      as a modifier of GlcAT-P and loss or reduction of repo function in a GlcAT-P
      mutant background enhances VNC elongation. We propose a model in which hemocytes
      are required for aspects of glial cell biology which in turn affects the
      elongation of peripheral nerves during larval development. Our data also
      identifies GlcAT-P as a first candidate gene involved in growth of integrated
      peripheral nerves and therefore establishes Drosophila as an amenable in-vivo
      model system to study this process at the cellular and molecular level in more
      detail.

PMID- 22132224
TI  - Gift card incentives and non-response bias in a survey of vaccine providers: the
      role of geographic and demographic factors.
AB  - This study investigates the effects of non-response bias in a 2010 postal survey
      assessing experiences with H1N1 influenza vaccine administration among a diverse
      sample of providers (N = 765) in Washington state. Though we garnered a high
      response rate (80.9%) by using evidence-based survey design elements, including
      intensive follow-up and a gift card incentive from Target, non-response bias
      could exist if there were differences between respondents and non-respondents. We
      investigated differences between the two groups for seven variables: road
      distance to the nearest Target store, practice type, previous administration of
      vaccines, region, urbanicity, size of practice, and Vaccines for Children (VFC)
      program enrollment. We also examined the effect of non-response bias on survey
      estimates. Statistically significant differences between respondents and non
      respondents were found for four variables: miles to the nearest Target store,
      type of medical practice, whether the practice routinely administered additional
      vaccines besides H1N1, and urbanicity. Practices were more likely to respond if
      they were from a small town or rural area (OR = 7.68, 95% CI = 1.44-40.88), were
      a non-traditional vaccine provider type (OR = 2.08, 95% CI = 1.06-4.08) or a
      pediatric provider type (OR = 4.03, 95% CI = 1.36-11.96), or administered
      additional vaccines besides H1N1 (OR = 1.80, 95% CI = 1.03-3.15). Of particular
      interest, for each ten mile increase in road distance from the nearest Target
      store, the likelihood of provider response decreased (OR = 0.73, 95% CI = 0.60
      0.89). Of those variables associated with response, only small town or rural
      practice location was associated with a survey estimate of interest, suggesting
      that non-response bias had a minimal effect on survey estimates. These findings
      show that gift card incentives alongside survey design elements and follow-up can
      achieve high response rates. However, there is evidence that practices farther
      from the nearest place to redeem gift cards may be less likely to respond to the
      survey.

PMID- 22132226
TI  - Toxicity associated with stavudine dose reduction from 40 to 30 mg in first-line
      antiretroviral therapy.
AB  - BACKGROUND: To compare the incidence and timing of toxicity associated with the
      use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral
      therapy (ART) for HIV treatment and to investigate associated risk factors.
      METHODS: Multicohort study including 23 HIV programs in resource-limited
      countries. Adults enrolled between January 2005 and December 2009. Four-year
      rates of all-cause and stavudine-specific toxicity were estimated. Multilevel
      mixed-effect Poisson and accelerated failure models were used to investigate
      factors associated with toxicity and timing of diagnosis. FINDINGS: A total of
      48,785 patients contributed 62,505 person-years of follow-up. Rate of all-cause
      toxicity was 7.80 (95%CI 7.59-8.03) per 100 person-years, but varied greatly
      across sites (range 0.41-21.76). Patients treated with stavudine 40 mg had higher
      rates of toxicity (adjusted rate ratio [aRR] 1.18, 95%CI 1.06-1.30 during the
      first year of ART; and 1.51, 95%CI 1.32-1.71 during the second year). Women,
      older age, initial advanced clinical stage, and low CD4 count were associated
      with increased toxicity rate ratios. Timing of lipodystrophy and peripheral
      neuropathy diagnosis were 12% and 13% shorter, respectively, in patients treated
      with stavudine 40 mg than in those receiving 30 mg stavudine dose (P = 0.03 and
      0.07, respectively).  INSTERPRETATION: Higher rates of drug-related toxicity were
      reported in patients receiving stavudine 40 mg compared with 30 mg, and the time
      to toxicity diagnosis was shorter in patients treated with the higher dose.
      Higher rates of toxicity were observed during the first two years of ART.

PMID- 22132225
TI  - Microarray-based transcriptomic analysis of differences between long-term
      gregarious and solitarious desert locusts.
AB  - Desert locusts (Schistocerca gregaria) show an extreme form of phenotypic
      plasticity and can transform between a cryptic solitarious phase and a swarming
      gregarious phase. The two phases differ extensively in behavior, morphology and
      physiology but very little is known about the molecular basis of these
      differences. We used our recently generated Expressed Sequence Tag (EST) database
      derived from S. gregaria central nervous system (CNS) to design oligonucleotide
      microarrays and compare the expression of thousands of genes in the CNS of long
      term gregarious and solitarious adult desert locusts. This identified 214
      differentially expressed genes, of which 40% have been annotated to date. These
      include genes encoding proteins that are associated with CNS development and
      modeling, sensory perception, stress response and resistance, and fundamental
      cellular processes. Our microarray analysis has identified genes whose altered
      expression may enable locusts of either phase to deal with the different
      challenges they face. Genes for heat shock proteins and proteins which confer
      protection from infection were upregulated in gregarious locusts, which may allow
      them to respond to acute physiological challenges. By contrast the longer-lived
      solitarious locusts appear to be more strongly protected from the slowly
      accumulating effects of ageing by an upregulation of genes related to anti
      oxidant systems, detoxification and anabolic renewal. Gregarious locusts also had
      a greater abundance of transcripts for proteins involved in sensory processing
      and in nervous system development and plasticity. Gregarious locusts live in a
      more complex sensory environment than solitarious locusts and may require a
      greater turnover of proteins involved in sensory transduction, and possibly
      greater neuronal plasticity.

PMID- 22132227
TI  - Design and analysis of rhesus cytomegalovirus IL-10 mutants as a model for novel
      vaccines against human cytomegalovirus.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) expresses a viral ortholog (CMVIL-10) of
      human cellular interleukin-10 (cIL-10). Despite only ~26% amino acid sequence
      identity, CMVIL-10 exhibits comparable immunosuppressive activity with cIL-10,
      attenuates HCMV antiviral immune responses, and contributes to lifelong
      persistence within infected hosts. The low sequence identity between CMVIL-10 and
      cIL-10 suggests vaccination with CMVIL-10 may generate antibodies that
      specifically neutralize CMVIL-10 biological activity, but not the cellular
      cytokine, cIL-10. However, immunization with functional CMVIL-10 might be
      detrimental to the host because of its immunosuppressive properties. METHODS AND
      FINDINGS: Structural biology was used to engineer biologically inactive mutants
      of CMVIL-10 that would, upon vaccination, elicit a potent immune response to the
      wild-type viral cytokine. To test the designed proteins, the mutations were
      incorporated into the rhesus cytomegalovirus (RhCMV) ortholog of CMVIL-10
      (RhCMVIL-10) and used to vaccinate RhCMV-infected rhesus macaques. Immunization
      with the inactive RhCMVIL-10 mutants stimulated antibodies against wild-type
      RhCMVIL-10 that neutralized its biological activity, but did not cross-react with
      rhesus cellular IL-10. CONCLUSION: This study demonstrates an immunization
      strategy to neutralize RhCMVIL-10 biological activity using non-functional
      RhCMVIL-10 antigens. The results provide the methodology for targeting CMVIL-10
      in vaccine, and therapeutic strategies, to nullify HCMV's ability to (1) skew
      innate and adaptive immunity, (2) disseminate from the site of primary mucosal
      infection, and (3) establish a lifelong persistent infection.

PMID- 22132229
TI  - Microbial biogeography of public restroom surfaces.
AB  - We spend the majority of our lives indoors where we are constantly exposed to
      bacteria residing on surfaces. However, the diversity of these surface-associated
      communities is largely unknown. We explored the biogeographical patterns
      exhibited by bacteria across ten surfaces within each of twelve public restrooms.
      Using high-throughput barcoded pyrosequencing of the 16 S rRNA gene, we
      identified 19 bacterial phyla across all surfaces. Most sequences belonged to
      four phyla: Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria. The
      communities clustered into three general categories: those found on surfaces
      associated with toilets, those on the restroom floor, and those found on surfaces
      routinely touched with hands. On toilet surfaces, gut-associated taxa were more
      prevalent, suggesting fecal contamination of these surfaces. Floor surfaces were
      the most diverse of all communities and contained several taxa commonly found in
      soils. Skin-associated bacteria, especially the Propionibacteriaceae, dominated
      surfaces routinely touched with our hands. Certain taxa were more common in
      female than in male restrooms as vagina-associated Lactobacillaceae were widely
      distributed in female restrooms, likely from urine contamination. Use of the
      SourceTracker algorithm confirmed many of our taxonomic observations as human
      skin was the primary source of bacteria on restroom surfaces. Overall, these
      results demonstrate that restroom surfaces host relatively diverse microbial
      communities dominated by human-associated bacteria with clear linkages between
      communities on or in different body sites and those communities found on restroom
      surfaces. More generally, this work is relevant to the public health field as we
      show that human-associated microbes are commonly found on restroom surfaces
      suggesting that bacterial pathogens could readily be transmitted between
      individuals by the touching of surfaces. Furthermore, we demonstrate that we can
      use high-throughput analyses of bacterial communities to determine sources of
      bacteria on indoor surfaces, an approach which could be used to track pathogen
      transmission and test the efficacy of hygiene practices.

PMID- 22132228
TI  - Chronic stress induces sex-specific alterations in methylation and expression of
      corticotropin-releasing factor gene in the rat.
AB  - BACKGROUND: Although the higher prevalence of depression in women than in men is
      well known, the neuronal basis of this sex difference is largely elusive.
      METHODS: Male and female rats were exposed to chronic variable mild stress (CVMS)
      after which immediate early gene products, corticotropin-releasing factor (CRF)
      mRNA and peptide, various epigenetic-associated enzymes and DNA methylation of
      the Crf gene were determined in the hypothalamic paraventricular nucleus (PVN),
      oval (BSTov) and fusiform (BSTfu) parts of the bed nucleus of the stria
      terminalis, and central amygdala (CeA). RESULTS: CVMS induced site-specific
      changes in Crf gene methylation in all brain centers studied in female rats and
      in the male BST and CeA, whereas the histone acetyltransferase, CREB-binding
      protein was increased in the female BST and the histone-deacetylase-5 decreased
      in the male CeA. These changes were accompanied by an increased amount of c-Fos
      in the PVN, BSTfu and CeA in males, and of FosB in the PVN of both sexes and in
      the male BSTov and BSTfu. In the PVN, CVMS increased CRF mRNA in males and CRF
      peptide decreased in females. CONCLUSIONS: The data confirm our hypothesis that
      chronic stress affects gene expression and CRF transcriptional, translational and
      secretory activities in the PVN, BSTov, BSTfu and CeA, in a brain center-specific
      and sex-specific manner. Brain region-specific and sex-specific changes in
      epigenetic activity and neuronal activation may play, too, an important role in
      the sex specificity of the stress response and the susceptibility to depression.

PMID- 22132230
TI  - In vitro effects of pirfenidone on cardiac fibroblasts: proliferation,
      myofibroblast differentiation, migration and cytokine secretion.
AB  - Cardiac fibroblasts (CFs) are the primary cell type responsible for cardiac
      fibrosis during pathological myocardial remodeling. Several studies have
      illustrated that pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) attenuates
      cardiac fibrosis in different animal models. However, the effects of pirfenidone
      on cardiac fibroblast behavior have not been examined. In this study, we
      investigated whether pirfenidone directly modulates cardiac fibroblast behavior
      that is important in myocardial remodeling such as proliferation, myofibroblast
      differentiation, migration and cytokine secretion. Fibroblasts were isolated from
      neonatal rat hearts and bioassays were performed to determine the effects of
      pirfenidone on fibroblast function. We demonstrated that treatment of CFs with
      pirfenidone resulted in decreased proliferation, and attenuated fibroblast alpha
      smooth muscle actin expression and collagen contractility. Boyden chamber assay
      illustrated that pirfenidone inhibited fibroblast migration ability, probably by
      decreasing the ratio of matrix metalloproteinase-9 to tissue inhibitor of
      metalloproteinase-1. Furthermore, pirfenidone attenuated the synthesis and
      secretion of transforming growth factor-beta1 but elevated that of interleukin
      10. These direct and pleiotropic effects of pirfenidone on cardiac fibroblasts
      point to its potential use in the treatment of adverse myocardial remodeling.

PMID- 22132231
TI  - Dietary deficiency of essential amino acids rapidly induces cessation of the rat
      estrous cycle.
AB  - Reproductive functions are regulated by the sophisticated coordination between
      the neuronal and endocrine systems and are sustained by a proper nutritional
      environment. Female reproductive function is vulnerable to effects from dietary
      restrictions, suggesting a transient adaptation that prioritizes individual
      survival over reproduction until a possible future opportunity for satiation.
      This adaptation could also partially explain the existence of amenorrhea in women
      with anorexia nervosa. Because amino acid nutritional conditions other than
      caloric restriction uniquely alters amino acid metabolism and affect the hormonal
      levels of organisms, we hypothesized that the supply of essential amino acids in
      the diet plays a pivotal role in the maintenance of the female reproductive
      system. To test this hypothesis, we examined ovulatory cyclicity in female rats
      under diets that were deficient in threonine, lysine, tryptophan, methionine or
      valine. Ovulatory cyclicity was monitored by daily cytological evaluations of
      vaginal smears. After continuous feeding of the deficient diet, a persistent
      diestrus or anovulatory state was induced most quickly by the valine-deficient
      diet and most slowly by the lysine-deficient diet. A decline in the systemic
      insulin-like growth factor 1 level was associated with a dietary amino acid
      deficiency. Furthermore, a paired group of rats that were fed an isocaloric diet
      with balanced amino acids maintained normal estrous cyclicity. These disturbances
      of the estrous cycle by amino acid deficiency were quickly reversed by the
      consumption of a normal diet. The continuous anovulatory state in this study is
      not attributable to a decrease in caloric intake but to an imbalance in the
      dietary amino acid composition. With a shortage of well-balanced amino acid
      sources, reproduction becomes risky for both the mother and the fetus. It could
      be viewed as an adaptation to the diet, diverting resources away from
      reproduction and reallocating them to survival until well-balanced amino acid
      sources are found.

PMID- 22132232
TI  - Synergy analysis reveals association between insulin signaling and desmoplakin
      expression in palmitate treated HepG2 cells.
AB  - The regulation of complex cellular activities in palmitate treated HepG2 cells,
      and the ensuing cytotoxic phenotype, involves cooperative interactions between
      genes. While previous approaches have largely focused on identifying individual
      target genes, elucidating interacting genes has thus far remained elusive. We
      applied the concept of information synergy to reconstruct a "gene-cooperativity"
      network for palmititate-induced cytotoxicity in liver cells. Our approach
      integrated gene expression data with metabolic profiles to select a subset of
      genes for network reconstruction. Subsequent analysis of the network revealed
      insulin signaling as the most significantly enriched pathway, and desmoplakin
      (DSP) as its top neighbor. We determined that palmitate significantly reduces DSP
      expression, and treatment with insulin restores the lost expression of DSP.
      Insulin resistance is a common pathological feature of fatty liver and related
      ailments, whereas loss of DSP has been noted in liver carcinoma. Reduced DSP
      expression can lead to loss of cell-cell adhesion via desmosomes, and disrupt the
      keratin intermediate filament network. Our findings suggest that DSP expression
      may be perturbed by palmitate and, along with insulin resistance, may play a role
      in palmitate induced cytotoxicity, and serve as potential targets for further
      studies on non-alcoholic fatty liver disease (NAFLD).

PMID- 22132233
TI  - Protoplast transformation of recalcitrant alkaliphilic Bacillus sp. with
      methylated plasmid DNA and a developed hard agar regeneration medium.
AB  - Among the diverse alkaliphilic Bacillus strains, only a little have been reported
      to be genetically transformed. In this study, an efficient protoplast
      transformation procedure was developed for recalcitrant alkaliphilic Bacillus sp.
      N16-5. The procedure involved polyethylene glycol-induced DNA uptake by the
      protoplasts and subsequent protoplast regeneration with a developed hard agar
      regeneration medium. An in vivo methylation strategy was introduced to methylate
      the exogenous plasmid DNA for improving the transformation efficiency. The
      transformation efficiency reached to 1.1*10(5) transformants per ug plasmid DNA
      with methylated plasmid pHCMC04 and the developed hard agar regeneration medium.
      This procedure might also be applicable to the genetic transformation of other
      Bacillus strains.

PMID- 22132234
TI  - Self-organizing circuit assembly through spatiotemporally coordinated neuronal
      migration within geometric constraints.
AB  - BACKGROUND: Neurons are dynamically coupled with each other through neurite
      mediated adhesion during development. Understanding the collective behavior of
      neurons in circuits is important for understanding neural development. While a
      number of genetic and activity-dependent factors regulating neuronal migration
      have been discovered on single cell level, systematic study of collective
      neuronal migration has been lacking. Various biological systems are shown to be
      self-organized, and it is not known if neural circuit assembly is self-organized.
      Besides, many of the molecular factors take effect through spatial patterns, and
      coupled biological systems exhibit emergent property in response to geometric
      constraints. How geometric constraints of the patterns regulate neuronal
      migration and circuit assembly of neurons within the patterns remains unexplored.
      METHODOLOGY/PRINCIPAL FINDINGS: We established a two-dimensional model for
      studying collective neuronal migration of a circuit, with hippocampal neurons
      from embryonic rats on Matrigel-coated self-assembled monolayers (SAMs). When the
      neural circuit is subject to geometric constraints of a critical scale, we found
      that the collective behavior of neuronal migration is spatiotemporally
      coordinated. Neuronal somata that are evenly distributed upon adhesion tend to
      aggregate at the geometric center of the circuit, forming mono-clusters.
      Clustering formation is geometry-dependent, within a critical scale from 200 um
      to approximately 500 um. Finally, somata clustering is neuron-type specific, and
      glutamatergic and GABAergic neurons tend to aggregate homo-philically.
      CONCLUSIONS/SIGNIFICANCE: We demonstrate self-organization of neural circuits in
      response to geometric constraints through spatiotemporally coordinated neuronal
      migration, possibly via mechanical coupling. We found that such collective
      neuronal migration leads to somata clustering, and mono-cluster appears when the
      geometric constraints fall within a critical scale. The discovery of geometry
      dependent collective neuronal migration and the formation of somata clustering in
      vitro shed light on neural development in vivo.

PMID- 22132236
TI  - Severely impaired learning and altered neuronal morphology in mice lacking NMDA
      receptors in medium spiny neurons.
AB  - The striatum is composed predominantly of medium spiny neurons (MSNs) that
      integrate excitatory, glutamatergic inputs from the cortex and thalamus, and
      modulatory dopaminergic inputs from the ventral midbrain to influence behavior.
      Glutamatergic activation of AMPA, NMDA, and metabotropic receptors on MSNs is
      important for striatal development and function, but the roles of each of these
      receptor classes remain incompletely understood. Signaling through NMDA-type
      glutamate receptors (NMDARs) in the striatum has been implicated in various motor
      and appetitive learning paradigms. In addition, signaling through NMDARs
      influences neuronal morphology, which could underlie their role in mediating
      learned behaviors. To study the role of NMDARs on MSNs in learning and in
      morphological development, we generated mice lacking the essential NR1 subunit,
      encoded by the Grin1 gene, selectively in MSNs. Although these knockout mice
      appear normal and display normal 24-hour locomotion, they have severe deficits in
      motor learning, operant conditioning and active avoidance. In addition, the MSNs
      from these knockout mice have smaller cell bodies and decreased dendritic length
      compared to littermate controls. We conclude that NMDAR signaling in MSNs is
      critical for normal MSN morphology and many forms of learning.

PMID- 22132235
TI  - Genomic sequence analysis of granulovirus isolated from the tobacco cutworm,
      Spodoptera litura.
AB  - BACKGROUND: Spodoptera litura is a noctuid moth that is considered an
      agricultural pest. The larvae feed on a wide range of plants and have been
      recorded on plants from 40 plant families (mostly dicotyledons). It is a major
      pest of many crops. To better understand Spodoptera litura granulovirus (SpliGV),
      the nucleotide sequence of the SpliGV DNA genome was determined and analyzed.
      METHODOLOGY/PRINCIPAL FINDINGS: The genome of the SpliGV was completely
      sequenced. The nucleotide sequence of the SpliGV genome was 124,121 bp long with
      61.2% A+T content and contained 133 putative open reading frames (ORFs) of 150 or
      more nucleotides. The 133 putative ORFs covered 86.3% of the genome. Among these,
      31 ORFs were conserved in most completely sequenced baculovirus genomes, 38 were
      granulovirus (GV)-specific, and 64 were present in some nucleopolyhedroviruses
      (NPVs) and/or GVs. We proved that 9 of the ORFs were SpliGV specific.
      CONCLUSIONS/SIGNIFICANCE: The genome of SpliGV is 124,121 bp in size. One hundred
      thirty-three ORFs that putatively encode proteins of 50 or more amino acid
      residues with minimal overlap were determined. No chitinase or cathepsin genes,
      which are involved in the liquefaction of the infected host, were found in the
      SpliGV genome, explaining why SpliGV-infected insects do not degrade in a typical
      manner. The DNA photolyase gene was first found in the genus Granulovirus. When
      phylogenic relationships were analyzed, the SpliGV was most closely related to
      Trichoplusia ni granulovirus (TnGV) and Xestia c-nigrum granulovirus (XecnGV),
      which belong to the Type I-granuloviruses (Type I-GV).

PMID- 22132238
TI  - Phylogenomics of Reichenowia parasitica, an alphaproteobacterial endosymbiont of
      the freshwater leech Placobdella parasitica.
AB  - Although several commensal alphaproteobacteria form close relationships with
      plant hosts where they aid in (e.g.,) nitrogen fixation and nodulation, only a
      few inhabit animal hosts. Among these, Reichenowia picta, R. ornata and R.
      parasitica, are currently the only known mutualistic, alphaproteobacterial
      endosymbionts to inhabit leeches. These bacteria are harbored in the epithelial
      cells of the mycetomal structures of their freshwater leech hosts, Placobdella
      spp., and these structures have no other obvious function than housing bacterial
      symbionts. However, the function of the bacterial symbionts has remained unclear.
      Here, we focused both on exploring the genomic makeup of R. parasitica and on
      performing a robust phylogenetic analysis, based on more data than previous
      hypotheses, to test its position among related bacteria. We sequenced a combined
      pool of host and symbiont DNA from 36 pairs of mycetomes and performed an in
      silico separation of the different DNA pools through subtractive scaffolding. The
      bacterial contigs were compared to 50 annotated bacterial genomes and the genome
      of the freshwater leech Helobdella robusta using a BLASTn protocol. Further,
      amino acid sequences inferred from the contigs were used as queries against the
      50 bacterial genomes to establish orthology. A total of 358 orthologous genes
      were used for the phylogenetic analyses. In part, results suggest that R.
      parasitica possesses genes coding for proteins related to nitrogen fixation,
      iron/vitamin B translocation and plasmid survival. Our results also indicate that
      R. parasitica interacts with its host in part by transmembrane signaling and that
      several of its genes show orthology across Rhizobiaceae. The phylogenetic
      analyses support the nesting of R. parasitica within the Rhizobiaceae, as sister
      to a group containing Agrobacterium and Rhizobium species.

PMID- 22132237
TI  - Optimization of a low cost and broadly sensitive genotyping assay for HIV-1 drug
      resistance surveillance and monitoring in resource-limited settings.
AB  - Commercially available HIV-1 drug resistance (HIVDR) genotyping assays are
      expensive and have limitations in detecting non-B subtypes and circulating
      recombinant forms that are co-circulating in resource-limited settings (RLS).
      This study aimed to optimize a low cost and broadly sensitive in-house assay in
      detecting HIVDR mutations in the protease (PR) and reverse transcriptase (RT)
      regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N =
      96). Compared to the original in-house assay and two commercially available
      genotyping systems, TRUGENE(r) and ViroSeq(r), the optimized in-house assay
      showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively.
      The optimized in-house assay was more sensitive in detecting mixture bases than
      the original in-house (N = 87, P<0.001) and TRUGENE(r) and ViroSeq(r) assays.
      When the optimized in-house assay was applied to genotype samples collected for
      HIVDR surveys (N = 230), all 72 (100%) plasma and 69 (95.8%) of the matched dried
      blood spots (DBS) in the Vietnam transmitted HIVDR survey were genotyped and
      nucleotide sequence concordance was 98.8%; Testing of treatment-experienced
      patient plasmas with viral load (VL) >= and <3 log10 copies/ml from the Nigeria
      and Malawi surveys yielded 100% (N = 46) and 78.6% (N = 14) genotyping rates,
      respectively. Furthermore, all 18 matched DBS stored at room temperature from the
      Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences
      revealed that 43.6% were CRF01_AE, 25.9% subtype C, 13.1% CRF02_AG, 5.1% subtype
      G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4%
      each CRF06_CPX, CRF07_BC and CRF09_CPX. CONCLUSIONS: The optimized in-house assay
      is broadly sensitive in genotyping HIV-1 group M viral strains and more sensitive
      than the original in-house, TRUGENE(r) and ViroSeq(r) in detecting mixed viral
      populations. The broad sensitivity and substantial reagent cost saving make this
      assay more accessible for RLS where HIVDR surveillance is recommended to minimize
      the development and transmission of HIVDR.

PMID- 22132239
TI  - Characterization of organics consistent with beta-chitin preserved in the Late
      Eocene cuttlefish Mississaepia mississippiensis.
AB  - BACKGROUND: Preservation of original organic components in fossils across
      geological time is controversial, but the potential such molecules have for
      elucidating evolutionary processes and phylogenetic relationships is invaluable.
      Chitin is one such molecule. Ancient chitin has been recovered from both
      terrestrial and marine arthropods, but prior to this study had not been recovered
      from fossil marine mollusks. METHODOLOGY/PRINCIPAL FINDINGS: Organics consistent
      with beta-chitin are recovered in cuttlebones of Mississaepia mississippiensis
      from the Late Eocene (34.36 million years ago) marine clays of Hinds County,
      Mississippi, USA. These organics were determined and characterized through
      comparisons with extant taxa using Scanning Electron Microscopy/Energy Dispersive
      Spectrometry (SEM/EDS), Field Emission Scanning Electron Microscopy (Hyperprobe),
      Fourier Transmission Infrared Spectroscopy (FTIR) and Immunohistochemistry (IHC).
      CONCLUSIONS/SIGNIFICANCE: Our study presents the first evidence for organics
      consistent with chitin from an ancient marine mollusk and discusses how these
      organics have been degraded over time. As mechanisms for their preservation, we
      propose that the inorganic/organic lamination of the cuttlebone, combined with a
      suboxic depositional environment with available free Fe(2+) ions, inhibited
      microbial or enzymatic degradation.

PMID- 22132241
TI  - The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and
      TLR9 up-regulation and confers increased B-cell proliferation.
AB  - In humans, allelic variants in Toll-like receptors (TLRs) associate with several
      pathologies. However, the underlying cellular and molecular mechanisms of this
      association remain largely unknown. Analysis of the human TLR9 promoter revealed
      that the C allele of the rs5743836 polymorphism generates several regulatory
      sites, including an IL-6-responding element. Here, we show that, in mononuclear
      cells carrying the TC genotype of rs5743836, IL-6 up-regulates TLR9 expression,
      leading to exacerbated cellular responses to CpG, including IL-6 production and B
      cell proliferation. Our study uncovers a role for the rs5743836 polymorphism in B
      cell biology with implications on TLR9-mediated diseases and on the therapeutic
      usage of TLR9 agonists/antagonists.

PMID- 22132240
TI  - Activation of epidermal growth factor receptor is required for NTHi-induced NF
      kappaB-dependent inflammation.
AB  - BACKGROUND: Inflammation is a hallmark of many serious human diseases.
      Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen causing
      respiratory tract infections in both adults and children. NTHi infections are
      characterized by inflammation, which is mainly mediated by nuclear transcription
      factor-kappa B (NF-kappaB)-dependent production of proinflammatory mediators.
      Epidermal growth factor receptor (EGFR) has been shown to play important roles in
      regulating diverse biological processes, including cell growth, differentiation,
      apoptosis, adhesion, and migration. Its role in regulating NF-kappaB activation
      and inflammation, however, remains largely unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: In the present study, we demonstrate that EGFR plays a vital role in
      NTHi-induced NF-kappaB activation and the subsequent induction of proinflammatory
      mediators in human middle ear epithelial cells and other cell types. Importantly,
      we found that AG1478, a specific tyrosine kinase inhibitor of EGFR potently
      inhibited NTHi-induced inflammatory responses in the middle ears and lungs of
      mice in vivo. Moreover, we found that MKK3/6-p38 and PI3K/Akt signaling pathways
      are required for mediating EGFR-dependent NF-kappaB activation and inflammatory
      responses by NTHi. CONCLUSIONS/SIGNIFICANCE: Here, we provide direct evidence
      that EGFR plays a critical role in mediating NTHi-induced NF-kappaB activation
      and inflammation in vitro and in vivo. Given that EGFR inhibitors have been
      approved in clinical use for the treatment of cancers, current studies will not
      only provide novel insights into the molecular mechanisms underlying the
      regulation of inflammation, but may also lead to the development of novel
      therapeutic strategies for the treatment of respiratory inflammatory diseases and
      other inflammatory diseases.

PMID- 22132242
TI  - Solid-State P and H NMR Investigations of Amorphous and Crystalline Calcium
      Phosphates Grown Biomimetically From a Mesoporous Bioactive Glass.
AB  - By exploiting (1)H and (31)P magic-angle spinning nuclear magnetic resonance
      (NMR) spectroscopy, we explore the proton and orthophosphate environments in
      biomimetic amorphous calcium phosphate (ACP) and hydroxy-apatite (HA), as grown
      in vitro at the surface of a 10CaO-85SiO(2)-5P(2)O(5) mesoporous bioactive glass
      (MBG) in either a simulated body fluid or buffered water. Transmission electron
      microscopy confirmed the presence of a calcium phosphate layer comprising
      nanocrystalline HA. Two-dimensional (1)H-(31)P heteronuclear correlation NMR
      established predominantly (1)H(2)O<->(31)PO(4) (3-) and O(1)H<->(31)PO(4) (3-)
      contacts in the amorphous and crystalline component, respectively, of the MBG
      surface-layer; these two pairs exhibit distinctly different (1)H->(31)P cross
      polarization dynamics, revealing a twice as large squared effective (1)H-(31)P
      dipolar coupling constant in ACP compared with HA. These respective observations
      are mirrored in synthetic (well-crystalline) HA, and the amorphous calcium
      orthophosphate (CaP) clusters that are present in the pristine MBG pore walls:
      besides highlighting very similar local (1)H and (31)P environments in synthetic
      and biomimetic HA, our findings evidence closely related NMR characteristics, and
      thereby similar local structures, of the CaP clusters in the pristine MBG
      relative to biomimetic ACP.

PMID- 22132243
TI  - Larval development of Aedes aegypti and Aedes albopictus in peri-urban brackish
      water and its implications for transmission of arboviral diseases.
AB  - Aedes aegypti (Linnaeus) and Aedes albopictus Skuse mosquitoes transmit serious
      human arboviral diseases including yellow fever, dengue and chikungunya in many
      tropical and sub-tropical countries. Females of the two species have adapted to
      undergo preimaginal development in natural or artificial collections of
      freshwater near human habitations and feed on human blood. While there is an
      effective vaccine against yellow fever, the control of dengue and chikungunya is
      mainly dependent on reducing freshwater preimaginal development habitats of the
      two vectors. We show here that Ae. aegypti and Ae. albopictus lay eggs and their
      larvae survive to emerge as adults in brackish water (water with <0.5 ppt or
      parts per thousand, 0.5-30 ppt and >30 ppt salt are termed fresh, brackish and
      saline respectively). Brackish water with salinity of 2 to 15 ppt in discarded
      plastic and glass containers, abandoned fishing boats and unused wells in coastal
      peri-urban environment were found to contain Ae. aegypti and Ae. albopictus
      larvae. Relatively high incidence of dengue in Jaffna city, Sri Lanka was
      observed in the vicinity of brackish water habitats containing Ae. aegypti
      larvae. These observations raise the possibility that brackish water-adapted Ae.
      aegypti and Ae. albopictus may play a hitherto unrecognized role in transmitting
      dengue, chikungunya and yellow fever in coastal urban areas. National and
      international health authorities therefore need to take the findings into
      consideration and extend their vector control efforts, which are presently
      focused on urban freshwater habitats, to include brackish water larval
      development habitats.

PMID- 22132245
TI  - Detection of Echinococcus multilocularis in carnivores in Razavi Khorasan
      province, Iran using mitochondrial DNA.
AB  - BACKGROUND: Echinococcus multilocularis is the source of alveolar echinococcosis,
      a potentially fatal zoonotic disease. This investigation assessed the presence of
      E. multilocularis infection in definitive hosts in the Chenaran region of Razavi
      Khorasan Province, northeastern Iran. METHODOLOGY/PRINCIPAL FINDINGS: Fecal
      samples from 77 domestic and stray dogs and 14 wild carnivores were examined
      using the flotation/sieving method followed by multiplex PCR of mitochondrial
      genes. The intestinal scraping technique (IST) and the sedimentation and counting
      technique (SCT) revealed adult Echinococcus in the intestines of five of 10
      jackals and of the single wolf examined. Three jackals were infected only with E.
      multilocularis but two, and the wolf, were infected with both E. multilocularis
      and E. granulosus. Multiplex PCR revealed E. multilocularis, E. granulosus, and
      Taenia spp. in 19, 24, and 28 fecal samples, respectively. Echinococcus
      multilocularis infection was detected in the feces of all wild carnivores sampled
      including nine jackals, three foxes, one wolf, one hyena, and five dogs (6.5%).
      Echinococcus granulosus was found in the fecal samples of 16.9% of dogs, 66.7% of
      jackals, and all of the foxes, the wolf, and the hyena. The feces of 16 (21.8%)
      dogs, 7 of 9 (77.8%) jackals, and all three foxes, one wolf and one hyena were
      infected with Taenia spp. CONCLUSIONS/SIGNIFICANCE: The prevalence of E.
      multilocularis in wild carnivores of rural areas of the Chenaran region is high,
      indicating that the life cycle is being maintained in northeastern Iran with the
      red fox, jackal, wolf, hyena, and dog as definitive hosts.

PMID- 22132244
TI  - The salivary secretome of the tsetse fly Glossina pallidipes (Diptera:
      Glossinidae) infected by salivary gland hypertrophy virus.
AB  - BACKGROUND: The competence of the tsetse fly Glossina pallidipes (Diptera;
      Glossinidae) to acquire salivary gland hypertrophy virus (SGHV), to support virus
      replication and successfully transmit the virus depends on complex interactions
      between Glossina and SGHV macromolecules. Critical requisites to SGHV
      transmission are its replication and secretion of mature virions into the fly's
      salivary gland (SG) lumen. However, secretion of host proteins is of equal
      importance for successful transmission and requires cataloging of G. pallidipes
      secretome proteins from hypertrophied and non-hypertrophied SGs.
      METHODOLOGY/PRINCIPAL FINDINGS: After electrophoretic profiling and in-gel
      trypsin digestion, saliva proteins were analyzed by nano-LC-MS/MS.
      MaxQuant/Andromeda search of the MS data against the non-redundant (nr) GenBank
      database and a G. morsitans morsitans SG EST database, yielded a total of 521
      hits, 31 of which were SGHV-encoded. On a false discovery rate limit of 1% and
      detection threshold of least 2 unique peptides per protein, the analysis resulted
      in 292 Glossina and 25 SGHV MS-supported proteins. When annotated by the Blast2GO
      suite, at least one gene ontology (GO) term could be assigned to 89.9% (285/317)
      of the detected proteins. Five (~1.8%) Glossina and three (~12%) SGHV proteins
      remained without a predicted function after blast searches against the nr
      database. Sixty-five of the 292 detected Glossina proteins contained an N
      terminal signal/secretion peptide sequence. Eight of the SGHV proteins were
      predicted to be non-structural (NS), and fourteen are known structural (VP)
      proteins. CONCLUSIONS/SIGNIFICANCE: SGHV alters the protein expression pattern in
      Glossina. The G. pallidipes SG secretome encompasses a spectrum of proteins that
      may be required during the SGHV infection cycle. These detected proteins have
      putative interactions with at least 21 of the 25 SGHV-encoded proteins. Our
      findings opens venues for developing novel SGHV mitigation strategies to block
      SGHV infections in tsetse production facilities such as using SGHV-specific
      antibodies and phage display-selected gut epithelia-binding peptides.

PMID- 22132246
TI  - Accuracy of urine circulating cathodic antigen (CCA) test for Schistosoma mansoni
      diagnosis in different settings of Cote d'Ivoire.
AB  - BACKGROUND: Promising results have been reported for a urine circulating cathodic
      antigen (CCA) test for the diagnosis of Schistosoma mansoni. We assessed the
      accuracy of a commercially available CCA cassette test (designated CCA-A) and an
      experimental formulation (CCA-B) for S. mansoni diagnosis. METHODOLOGY: We
      conducted a cross-sectional survey in three settings of Cote d'Ivoire: settings A
      and B are endemic for S. mansoni, whereas S. haematobium co-exists in setting C.
      Overall, 446 children, aged 8-12 years, submitted multiple stool and urine
      samples. For S. mansoni diagnosis, stool samples were examined with triplicate
      Kato-Katz, whereas urine samples were tested with CCA-A. The first stool and
      urine samples were additionally subjected to an ether-concentration technique and
      CCA-B, respectively. Urine samples were examined for S. haematobium using a
      filtration method, and for microhematuria using Hemastix dipsticks. PRINCIPAL
      FINDINGS: Considering nine Kato-Katz as diagnostic 'gold' standard, the
      prevalence of S. mansoni in setting A, B and C was 32.9%, 53.1% and 91.8%,
      respectively. The sensitivity of triplicate Kato-Katz from the first stool and a
      single CCA-A test was 47.9% and 56.3% (setting A), 73.9% and 69.6% (setting B),
      and 94.2% and 89.6% (setting C). The respective sensitivity of a single CCA-B was
      10.4%, 29.9% and 75.0%. The ether-concentration technique showed a low
      sensitivity for S. mansoni diagnosis (8.3-41.0%). The specificity of CCA-A was
      moderate (76.9-84.2%); CCA-B was high (96.7-100%). The likelihood of a CCA-A
      color reaction increased with higher S. mansoni fecal egg counts (odds ratio:
      1.07, p<0.001). A concurrent S. haematobium infection or the presence of
      microhematuria did not influence the CCA-A test results for S. mansoni diagnosis.
      CONCLUSION/SIGNIFICANCE: CCA-A showed similar sensitivity than triplicate Kato
      Katz for S. mansoni diagnosis with no cross-reactivity to S. haematobium and
      microhematuria. The low sensitivity of CCA-B in our study area precludes its use
      for S. mansoni diagnosis.

PMID- 22132247
TI  - Dog bites in humans and estimating human rabies mortality in rabies endemic areas
      of Bhutan.
AB  - BACKGROUND: Dog bites in humans are a public health problem worldwide. The issues
      of increasing stray dog populations, rabies outbreaks, and the risk of dogs
      biting humans have been frequently reported by the media in Bhutan. This study
      aimed to estimate the bite incidence and identify the risk factors for dog bites
      in humans, and to estimate human deaths from rabies in rabies endemic south
      Bhutan. METHODS: A hospital-based questionnaire survey was conducted during 2009
      2010 among dog bites victims who visited three hospitals in Bhutan for anti
      rabies vaccine injection. Decision tree modeling was used to estimate human
      deaths from rabies following dog bite injuries in two rabies endemic areas of
      south Bhutan. RESULTS: Three hundred and twenty four dog bite victims were
      interviewed. The annual incidence of dog bites differed between the hospital
      catchment areas: 869.8 (95% CI: 722.8-1022.5), 293.8 (240-358.2) and 284.8 (251.2
      323) per 100,000 people in Gelephu, Phuentsholing and Thimphu, respectively.
      Males (62%) were more at risk than females (P<0.001). Children aged 5-9 years
      were bitten more than other age groups. The majority of victims (71%) were bitten
      by stray dogs. No direct fatal injury was reported. In two hospital areas
      (Gelephu and Phuentsholing) in south Bhutan the annual incidence of death from
      rabies was 3.14 (95% CI: 1.57-6.29) per 100,000 population. The decision tree
      model predicted an equivalent annual incidence of 4.67 (95% CI: 2.53-7.53)
      deaths/100,000 population at risk. In the absence of post exposure prophylaxis,
      the model predicted 19.24 (95% CI: 13.69-25.14) deaths/year in these two areas.
      CONCLUSIONS: Increased educational awareness of people about the risk of dog
      bites and rabies is necessary, particularly for children in rabies endemic areas
      of Bhutan.

PMID- 22132249
TI  - Management of extensive maxillofacial trauma with bony foreign body within the
      orbit from a chainsaw injury.
AB  - OBJECTIVE: The goal of this case report is to characterize injury patterns
      typical for chainsaw injuries to the face. We describe our approach to the soft
      tissue and skeletal injury patterns seen in these injuries. METHODS: We present a
      case report of a traumatic chainsaw injury to the face. RESULTS: A literature
      review of the typical injury patterns seen in chainsaw injuries to the face is
      discussed. Fractures to the bony orbit are on of the most common findings.
      Traumatic orbital fractures are often associated with other facial fractures,
      including those of the maxillary sinus and naso-orbital-ethmoid (NOE) region.
      There is a reported 47% incidence of lacrimal obstruction after NOE fractures,
      most caused by bone malposition or damage to the lacrimal sac or duct.
      Misdiagnosis of this injury pattern can lead to chronic patient morbidity.
      CONCLUSION: We present a case of traumatic orbital fracture with subsequent bony
      intrusion into the orbit, necessitating urgent exploration. The compound soft
      tissue and skeletal injury in this patient is typical for patients with
      associated lacrimal injury. Awareness of the injury patterns and treatment
      algorithms of these cases allows for appropriate assessment and intervention.

PMID- 22132248
TI  - A lipopeptide facilitate induction of Mycobacterium leprae killing in host cells.
AB  - Little is known of the direct microbicidal activity of T cells in leprosy, so a
      lipopeptide consisting of the N-terminal 13 amino acids lipopeptide (LipoK) of a
      33-kD lipoprotein of Mycobacterium leprae, was synthesized. LipoK activated M.
      leprae infected human dendritic cells (DCs) to induce the production of IL-12.
      These activated DCs stimulated autologous CD4+ or CD8+ T cells towards type 1
      immune response by inducing interferon-gamma secretion. T cell proliferation was
      also evident from the CFSE labeling of target CD4+ or CD8+ T cells. The direct
      microbicidal activity of T cells in the control of M. leprae multiplication is
      not well understood. The present study showed significant production of
      granulysin, granzyme B and perforin from these activated CD4+ and CD8+ T cells
      when stimulated with LipoK activated, M. leprae infected DCs. Assessment of the
      viability of M. leprae in DCs indicated LipoK mediated T cell-dependent killing
      of M. leprae. Remarkably, granulysin as well as granzyme B could directly kill M.
      leprae in vitro. Our results provide evidence that LipoK could facilitate M.
      leprae killing through the production of effector molecules granulysin and
      granzyme B in T cells.

PMID- 22132250
TI  - Arthrodesis using pedicled fibular flap after failed infected knee arthroplasty.
AB  - OBJECTIVE: Severe bone loss associated with failed revision total knee
      arthroplasty is a challenging scenario. The pedicled fibular flap is a method to
      obtain vascularized bone for use in knee arthrodesis after failure of a total
      knee arthroplasty, with substantial loss of bone. METHODS: We report 2 successful
      knee arthrodeses using this method in patients with infected, failed multiply
      revised total knee arthroplasties. The failed prosthesis was removed, and the
      bones were aligned and stabilized. The fibular flap was then harvested, fed
      through a subcutaneous tunnel, and placed within the medullary canal at the
      arthrodesis site. The soft tissue was closed over the grafts and flaps. RESULTS:
      Two elderly women presented with pain and drainage from previous total knee
      arthroplasties after multiple revisions. Arthrodeses were performed as described,
      and both patients were pain-free with the knee fused at 1 year. CONCLUSIONS:
      Thus, pedicled vascularized flaps are a viable alternative in the treatment of
      failed revision arthroplasty with large segmental bone loss.

PMID- 22132251
TI  - Chest wall reconstruction with strattice in an immunosuppressed patient.
AB  - We report successful reconstruction of a challenging composite chest wall defect
      in an immunocompromised patient using a biologic mesh. Infection results in
      significant morbidity and mortality in immunocompromised patients. Thus,
      reconstruction in this population requires careful selection of appropriate
      materials to repair the defect. A 26-year-old woman with a cardiac paraganglioma
      required resection of the heart, portions of the great vessels, several ribs, and
      a large portion of the sternum, with subsequent orthotopic cardiac
      transplantation. Titanium plates were used to restore sternal continuity and
      Strattice was used for chest wall reconstruction. Strattice was selected due to
      its ability to become incorporated and resist wound infection, to provide
      stability to the rib cage, and to protect the newly transplanted heart. In our
      experience, Strattice provides a viable alternative to other biologics and is a
      safer alternative to synthetic mesh for chest wall reconstruction in
      immunocompromised patients.

PMID- 22132252
TI  - Bioterrorism: preparing the plastic surgeon.
AB  - INTRODUCTION: Many medical disciplines, such as emergency medicine, trauma
      surgery, dermatology, psychiatry, family practice, and dentistry have documented
      attempts at assessing the level of bioterrorism preparedness in their
      communities. Currently, there is neither such an assessment nor an existing
      review of potential bioterrorism agents as they relate to plastic surgery.
      Therefore, the purpose of this article is to present plastic surgeons with a
      review of potential bioterrorism agents. METHODS: A review of the literature on
      bioterrorism agents and online resources of the Centers for Disease Control and
      Prevention was conducted. Category A agents were identified and specific
      attention was paid to the management issues that plastic surgeons might face in
      the event that these agents are used in an attack. RESULTS: Disease entities
      reviewed were smallpox, anthrax, plague, viral hemorrhagic fever, tularemia, and
      botulism. For each agent, we presented the microbiology, pathophysiology,
      clinical presentation, potential for weaponization, medical management, and
      surgical issues related to the plastic surgeon. CONCLUSION: This article is the
      first attempt at addressing preparedness for bioterrorism in the plastic surgery
      community. Many other fields have already started a similar process. This article
      represents a first step in developing evidence-based consensus guidelines and
      recommendations for the management of biological terrorism for plastic surgeons.

PMID- 22132253
TI  - Real data examples in statistical methods papers: Tremendously valuable, and also
      tremendously misvalued.
AB  - When a statistical methods paper is submitted to a journal for publication,
      examples in which the method is applied to real data are highly encouraged by
      many journals and in some cases are explicitly demanded. In this commentary, we
      argue that real data examples serve several useful purposes. However, we also
      argue that in many cases, particularly in the fields of genetics and genomics,
      there is an implicit or explicit expectation for examples to support purposes for
      which they are ill-suited and furthermore that these inappropriate expectations
      have negative consequences for the field. We conclude by noting that real data
      examples can be tremendously valuable and should continue to be used where
      appropriate, but that the demands for, expectations of, and conclusions drawn
      from them need to be scaled back.

PMID- 22132254
TI  - Clinical pearl: comedone extraction for persistent macrocomedones while on
      isotretinoin therapy.
AB  - In the past, the safety of performing procedures while patients are on
      isotretinoin has been questioned. Macrocomedones are traditionally resistant to
      treatment with isotretinoin alone. The authors present a technique that is safe
      to employ while patients are on isotretinoin to effectively eliminate
      macrocomedones without complication.

PMID- 22132255
TI  - Teeth in the line of fracture: to retain or remove?
AB  - The purpose of this study was to analyze mandibular fracture site, relationship
      of the fracture line to the periodontium, vitality of teeth, displacement of the
      fracture segments and their implications, and determine whether to retain or
      remove the teeth in the fracture line. Fifty patients with 62 fractures were
      involved in this study. An electric pulp tester was used to measure the pulpal
      response. The degree of fracture displacement and the relationship of the
      fracture line to the periodontium were evaluated using panoramic radiographs.
      Fractures of the parasymphysis region constituted a majority of 60.87% in the
      gross displacement category. Four of 50 patients showed no response presurgically
      and minimal response postoperatively on pulp vitality testing. Patients with
      teeth in the fracture line showing no response on pulp vitality testing should be
      advised extraction to avoid further complications.

PMID- 22132256
TI  - Isolated bilateral zygomatic complex and arch fracture: a rare case report.
AB  - This is an unusual case of isolated bilateral zygomatic complex and arch
      fracture, which is extremely rare. The literature has no such report of a case.

PMID- 22132258
TI  - Experience with the use of prebent plates for the reconstruction of mandibular
      defects.
AB  - Bending of large titanium plates for mandibular reconstruction is a tedious task.
      This is usually done by trial and error over an intraoperatively bent template.
      By means of rapid prototype technology, accurate three-dimensional models can be
      obtained. Using these models, it is possible to design, obtain, and adapt custom
      hardware for individual surgical cases. Reductions of operating room time when
      using this technology have been reported from 17% to 60%, with an average of 20%.
      This translates to reduction of cost and risks, improving the overall surgical
      outcome. The purpose of this article is to establish the indications and
      contraindication for the use three-dimensional models and prebent plates. We
      present our experience with five cases in which prebent reconstruction plates
      were used for mandibular reconstruction. No significant complications occurred,
      and satisfactory results were achieved in all cases. We found that the models
      required to obtain the hardware are extremely accurate, have multiple reported
      applications, and represent a valuable surgical tool in the planning and
      execution of reconstructive surgery.

PMID- 22132259
TI  - Mydriasis during Orbital Floor Fracture Reconstruction: A Novel Diagnostic and
      Treatment Algorithm.
AB  - Orbital floor fractures are the most commonly encountered traumatic fractures in
      the facial skeleton. Mydriasis that is detected during orbital floor fracture
      reconstruction may cause significant distress to surgeons, as it may be
      associated with sinister events such as visual loss. It is not an uncommon
      problem; previous studies have shown the incidence of mydriasis to be 2.1%. The
      combination of careful preoperative evaluation and planning, as well as specific
      intraoperative investigations when mydriasis is encountered, can be immensely
      valuable in allaying surgeons' anxiety during orbital floor fracture
      reconstruction. In this review article, the authors discuss the common causes of
      mydriasis and present a novel systematic approach to its diagnostic evaluation
      devised by our unit that has been successfully implemented since 2008.

PMID- 22132257
TI  - Postoperative care of the facial laceration.
AB  - The purpose of this investigation is to examine factors involved in the
      postoperative care of traumatic lacerations. An evidence-based comprehensive
      literature review was conducted. There are a limited number of scientifically
      proven studies that guide surgeons and emergency room physicians on postoperative
      care. Randomized controlled trials must be conducted to further standardize the
      postoperative protocol for simple facial lacerations.

PMID- 22132260
TI  - Repair of orbital floor fractures: our experience and new technical findings.
AB  - We report our experience with the repair of the orbital floor fractures and
      present new technical findings. We evaluated 30 subjects with pure blowout
      fractures treated at the Department of Maxillofacial Surgery of the Federico II
      University of Naples, Italy, between 2005 and 2007. A preoperative examination by
      computed tomography scans provided classification of the orbital floor fractures
      into small and large fractures by measurement of the bone defect to choose the
      appropriate reconstructive implant materials, resorbable or nonresorbable. The
      clinical follow-up has been performed at 1 week, 1 month, 3 months, and 6 months.
      We observed a resolution of preoperative symptoms. The scar was not evident, and
      there was an absence of postoperative complications. We concluded that the use of
      resorbable materials for small orbital floor fractures and nonresorbable
      materials for large orbital floor fractures offers satisfactory results in both
      functional and aesthetic considerations. Furthermore, the new technical findings
      allow standardization of the surgical technique to be more accurate, also
      reducing the economic costs.

PMID- 22132261
TI  - Treatment of Palatal Fractures by Osteosynthesis with 2.0-mm Locking Plates as
      External Fixator.
AB  - Treatment options for palatal fractures range from orthodontic braces, acrylic
      bars, and arch bars for maxillomandibular fixation to internal fixation, with
      plates and screws placed under the palate mucosa and periosteum, together with
      pyriform aperture or alveolar plating plus buttress reconstruction. Forty-five
      patients, ages 4 to 56, were treated using medium- or high-profile locking plates
      placed over the palatal mucosa as an external fixator for palatal fractures,
      together with treatment for other associated facial fractures. In open fractures,
      plates were placed after approximating the edges of the mucosal wounds. Plates
      and screws for palate fixation were removed at 12 weeks, when computed tomography
      scans provided evidence of fracture healing. All palatal fractures healed by 12
      weeks, with no cases of mucosal necrosis, bone exposure, fistulae, or infections.
      This approach achieves adequate stability, reduces the risk of bone and mucosal
      necrosis, and promotes healing of mucosal wounds in case of open fractures.

PMID- 22132262
TI  - Subcranial approach in pediatric craniofacial surgery.
AB  - We report our experience with the subcranial approach, developed at the Plastic
      Surgery Unit of Hospital "Ricardo Gutierrez," for the treatment of injuries in
      the frontoethmoidal orbital region in pediatric patients. The subcranial approach
      was described by Raveh et al for the treatment of fractures in the
      frontoethmoidal area. The subcranial approach was used later for surgery of
      tumors and deformities of the frontoethmoidal region. We have used this approach
      in nine cases of nontraumatic injuries (one meningioma, one orbital bone fibrous
      dysplasia, one vascular malformation, five nasal dermoid cysts, and one fronto
      orbital mucocele). One patient with vascular malformation died of a stroke 10
      days after surgery. The patient with the meningioma had a recurrence. Another
      patient developed an infection that needed surgical resolution and hardware
      removal. A third patient suffered a mild infection that receded with medication.
      No other complications were registered. The surgical exposure obtained through
      this approach was always excellent and left no cosmetic defects. There was no
      evidence of facial growth disturbance in this group of patients, except in one
      patient who received radiotherapy after surgery. Operative time and
      hospitalization were lower in this group than in patients with conventional
      frontal craniotomy.

PMID- 22132263
TI  - Ten Things You Didn't Know About the Journal of Graduate Medical Education.

PMID- 22132264
TI  - Publishing your education work in the journal of graduate medical education.

PMID- 22132265
TI  - Heightening residents' awareness of hand hygiene guidelines.

PMID- 22132266
TI  - First do no harm: preserving patient safety without sacrificing procedural
      education.

PMID- 22132267
TI  - Leadership development for program directors.
AB  - BACKGROUND: Residency program directors have increasingly challenging roles, but
      they may not be receiving adequate leadership development. OBJECTIVE: To assess
      and facilitate program directors' leadership self-awareness and development at a
      workshop retreat. METHODS: At our annual program director retreat, program
      directors and associate program directors from a variety of specialties completed
      the Thomas-Kilmann Conflict Mode Instrument (TKI), which evaluates an
      individual's behavior in conflict situations, and the Hersey-Blanchard
      Situational Leadership (HBSL) model, which measures individuals' preferred
      leadership style in working with followers. Participants received their results
      during the retreat and discussed their leadership style results in the context of
      conflict situations experienced in the past. An online survey was distributed 3
      weeks after the retreat to assess participant satisfaction and to determine
      whether participants would make changes to their leadership styles. RESULTS:
      Seventeen program directors attended the retreat and completed the tools. On the
      TKI, 47% preferred the Compromising mode for handling conflict, while 18%
      preferred either the Avoiding or Accommodating modes. On the HBSL, 71% of program
      directors preferred a Coaching leadership style. Ninety-one percent of
      postretreat-survey respondents found the leadership tools helpful and also
      thought they had a better awareness of their conflict mode and leadership style
      preferences. Eighty-two percent committed to a change in their leadership
      behaviors in the 6 months following the retreat. CONCLUSIONS: Leadership tools
      may be beneficial for promoting the professional development of program
      directors. The TKI and HBSL can be used within a local retreat or workshop as we
      describe to facilitate positive leadership-behavior changes.

PMID- 22132268
TI  - The morbidity and mortality conference: a unique opportunity for teaching
      empathic communication.
AB  - BACKGROUND: The morbidity and mortality conference is an educational tradition in
      American medicine that dates to the early 20th century. Traditionally, this
      conference has focused entirely on issues of diagnosis and treatment, in the
      context of a disappointing clinical outcome. INTERVENTION: We report on a new
      method for teaching empathic doctor-patient communication skills at an obstetrics
      and gynecology morbidity and mortality conference. For each case presented, we
      identified the communications challenges and allowed faculty and residents to
      "practice" the discussion they would have with the patient and the patient's
      family in that situation. In some sessions, actors assumed the role of the
      patient. Following the discussion of the case, we offered didactic presentations
      on how we communicate with patients and their families. These focused on
      techniques for being patient centered and included the use of body language, open
      ended questioning, reflective listening before offering to explain, and the
      importance of naming and validating emotions. RESULTS: The majority of
      participants felt the sessions to be helpful, and after one month many were able
      to identify a positive change in their interactions with patients. CONCLUSIONS:
      We believe that this unique teaching format allows learners to refine their
      communication skills in the context of situations that they know to be both
      realistic and important.

PMID- 22132269
TI  - Emotional Intelligence and the ACGME Competencies.
AB  - BACKGROUND: Residency programs desire assessment tools for teaching and measuring
      resident attainment of the Accreditation Council for Graduate Medical Education
      competencies, including interpersonal and communication skills. OBJECTIVE: We
      sought to evaluate the use of emotional intelligence (EI) assessment and training
      tools in assessing and enhancing interpersonal and communication skills. METHODS:
      We used a quasi-experimental design, with an intervention and control group
      composed of 1 class each of family medicine residents. The intervention was EI
      coaching. The assessment used the Emotional and Social Competence Inventory, a
      360-degree EI survey consisting of self and other (colleague) ratings for 12 EI
      competencies. RESULTS: There were 21 participants in each of the 3 assessments
      (test, posttest, and control). Our EI coaching intervention had very limited
      participation due to a lack of protected time for EI coaching and residents'
      competing obligations. Return rates for self surveys were 86% to 91% and 66% to
      68% for others. On all 3 trials, ratings by others were significantly higher than
      self ratings for every competence (range, P < .001-.045). None of the self
      ratings by the intervention group increased significantly for any of the
      competencies. None of the intervention group self ratings increased significantly
      on posttesting, whereas ratings by others increased significantly for
      coach/mentor (P < .001). The teamwork rating decreased significantly on both self
      and other ratings (P < .001). Achievement orientation was the highest
      intervention group posttest rating, and teamwork was the lowest. CONCLUSIONS: EI
      is a necessary skill in today's health care environment, and our study found that
      a tool from another sector was useful in assessing resident EI skills. Because
      our EI coaching intervention was unsuccessful, the effects of coaching on
      interpersonal and communication skills could not be assessed.

PMID- 22132270
TI  - Procedural readiness of pediatric interns: defining novice performance through
      simulation.
AB  - BACKGROUND: Pediatric lumbar puncture (LP) is a common invasive procedure
      performed by physicians in training. The Association of American Medical Colleges
      and the Accreditation Council for Graduate Medical Education recognize simulation
      as a tool for deliberate practice and standardized assessment of procedural
      performance. OBJECTIVE: We sought to perform a detailed review of simulated LP
      performance to elucidate reasons for pediatric residents' reported 26% failure
      rate. METHODS: Participants were enrolled in a single 30-minute session between
      July 2008 and January 2009. Data collected included former experience and
      training via questionnaire and video review of intern performance of a simulated
      LP on an infant model. Intern performance was assessed against a list of 10
      procedural elements. Acquisition of cerebrospinal fluid (CSF), the number of
      elements performed on the first 2 attempts, and specific types of
      training/experience were analyzed for associations. RESULTS: All 32 enrolled
      interns endorsed receiving some previous LP training. Training on a model was
      infrequent (38%). Interns reported performing a median of 2 LPs prior to
      enrollment (interquartile range, 2-4). Seven of 31 interns (22%) had yet to
      perform a live LP. Eleven of 32 interns (34%; 95% confidence interval [CI], 18%
      51%) acquired CSF during the first 2 simulated attempts. No specific type of
      prior training or experience was statistically associated with either the number
      of procedural elements or successful CSF acquisition (all P > .05). Interns
      performed a median of 7 of 10 procedural elements (interquartile range, 5.5-8).
      Early stylet removal was never performed. Complete removal of the stylet with all
      CSF checks was significantly associated with CSF acquisition (odds ratio, 9; 95%
      CI 0.98, 84.2). Avoidance of a spinous process upon skin entry was associated
      with a trend toward increased CSF acquisition (odds ratio, 3.5; 95% CI 0.76,
      16.1). CONCLUSION: Despite performing many common procedural elements, pediatric
      interns generally lack the ability to successfully acquire CSF during a simulated
      infant LP. Expert performance of an infant LP likely requires complete stylet
      removal with each check for CSF and early spinous process avoidance. A simulated
      infant LP allowed assessment of intern procedural performance as well as
      description of elements critical to successful CSF acquisition.

PMID- 22132271
TI  - Resident career planning needs in internal medicine: a qualitative assessment.
AB  - BACKGROUND: Few residency programs have centralized resources for career
      planning. As a consequence, little is known about residents' informational needs
      regarding career planning. OBJECTIVE: To examine career preparation stressors,
      practical needs, and information that residents wished they were privy to when
      applying. METHODS: In 2007 and 2008, we surveyed 163 recent graduates or
      graduating residents from 10 Yale-based and Yale-affiliated hospitals' internal
      medicine programs regarding their experiences with applying for positions after
      residency. We included questions about demographics, mentorship, stress of
      finding a job or fellowship, and open-ended questions to assess barriers and
      frustrations. Qualitative data were coded independently and a classification
      scheme was negotiated by consensus. RESULTS: A total of 89 residents or recent
      graduates responded, and 75% of them found career planning during residency
      training at least somewhat stressful. Themes regarding the application process
      included (1) knowledge about the process, (2) knowledge about career paths and
      opportunities, (3) time factors, (4) importance of adequate personal guidance and
      mentorship, and (5) self-knowledge regarding priorities and the desired outcome.
      Residents identified the following advice as most important: (1) start the
      process as early as possible and with a clear knowledge of the process timeline,
      (2) be clear about personal goals and priorities, and (3) be well-informed about
      a prospective employer and what that employer is looking for. Most residents felt
      career planning should be structured into the curriculum and should occur in the
      first year or throughout residency. CONCLUSIONS: This study highlights residents'
      desire for structured dissemination of information and counseling with regard to
      career planning during residency. Our data suggest that exposure to such
      resources may be beneficial as early as the first year of training.

PMID- 22132272
TI  - Rubric evaluation of pediatric emergency medicine fellows.
AB  - OBJECTIVES: To develop and validate a rubric assessment instrument for use by
      pediatric emergency medicine (PEM) faculty to evaluate PEM fellows and for
      fellows to use to self-assess. METHODS: This is a prospective study at a PEM
      fellowship program. The assessment instrument was developed through a multistep
      process: (1) development of rubric format items, scaled on the modified Dreyfus
      model proficiency levels, corresponding to the 6 Accreditation Council for
      Graduate Medical Education core competencies; (2) determination of content and
      construct validity of the items through structured input and item refinement by
      subject matter experts and focus group review; (3) collection of data using a 61
      item form; (4) evaluation of psychometrics; (5) selection of items for use in the
      final instrument. RESULTS: A total of 261 evaluations were collected from 2006 to
      2007; exploratory factor analysis yielded 5 factors with Eigenvalues >1.0; each
      contained >=4 items, with factor loadings >0.4 corresponding with the following
      competencies: (1) medical knowledge and practice-based learning and improvement,
      (2) patient care and systems-based practice, (3) interpersonal skills, (4)
      communication skills, and (5) professionalism. Cronbach alpha for the final 53
      item instrument was 0.989. There was also significant responsiveness of the tool
      to the year of training. CONCLUSION: A substantively and statistically validated
      rubric evaluation of PEM fellows is a reliable tool for formative and summative
      evaluation.

PMID- 22132273
TI  - Duty hour restrictions, ambulatory experience, and surgical procedural volume in
      obstetrics and gynecology.
AB  - BACKGROUND: Prior studies of resident experience in gynecology looked only at the
      year before and after adoption of ACGME duty hour standards. This study sought to
      determine whether procedure volume differed after completion of a 4-year
      residency training program, before and after work hour reform. METHOD: Inpatient
      and outpatient procedures performed by MetroHealth Medical Center/Cleveland
      Clinic program residents from 1998 to 2006 were obtained from Annual Reports of
      Institutional and Resident Experience. Four-year experience before and after duty
      hour restrictions were compared: hours worked were collected from resident
      schedules, ambulatory hours and procedures were compared directly, surgical
      procedures and deliveries were compared using a 2-tailed t test. Data were also
      obtained for institutional volume changes, and a corrected value, based on the
      rates of resident cases per available cases, was analyzed. RESULTS: Ambulatory
      hours worked per resident decreased after implementing work hour reform from 674
      to 366 hours. The types of ambulatory and surgical procedures performed varied
      over time. Overall, basic surgical and obstetrical volume per resident did not
      change before and after work hour reform (mean before reform, 723 +/- 117, mean
      after reform, 781 +/- 200, P  =  .58 for gynecologic procedures; mean before
      reform, 611 +/- 107, mean after reform, 535 +/- 73, P  =  .18 for basic
      obstetrics and vaginal and cesarean deliveries). Institutional volume did not
      change significantly, although the percentage of the institutions' cases
      performed by residents did decrease for some procedures. CONCLUSION: The ACGME
      duty hour restrictions do not limit the overall ambulatory or surgical procedural
      volume in an obstetrics and gynecology residency-training period.

PMID- 22132274
TI  - Incoming interns' perspectives on the institute of medicine recommendations for
      residents' duty hours.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) has
      announced revisions to the resident duty hour standards in light of a 2008
      Institute of Medicine report that recommended further limits. Soliciting resident
      input regarding the future of duty hours is critical to ensure trainee buy-in.
      PURPOSE: To assess incoming intern perceptions of duty hour restrictions at 3
      teaching hospitals. METHODS: We administered an anonymous survey to incoming
      interns during orientation at 3 teaching hospitals affiliated with 2 Midwestern
      medical schools in 2009. Survey questions assessed interns' perceptions of
      maximum shift length, days off, ACGME oversight, and preferences for a "fatigued
      post-call intern who admitted patient" versus "well-rested covering intern who
      just picked up patient" for various clinical scenarios. RESULTS: Eighty-six
      percent (299/346) of interns responded. Although 59% agreed that residents should
      not work over 16 hours without a break, 50% of interns favored the current
      limits. The majority (78%) of interns desired ability to exceed shift limit for
      rare cases or clinical opportunities. Most interns (90%) favored oversight by the
      ACGME, and 97% preferred a well-rested intern for performing a procedure.
      Meanwhile, only 48% of interns preferred a well-rested intern for discharging a
      patient or having an end of life discussion. Interns who favored 16-hour limits
      were less concerned with negative consequences of duty hour restrictions
      (handoffs, reduced clinical experience) and more likely to choose the well-rested
      intern for certain scenarios (odds ratio 2.33, 95% confidence interval 1.42-3.85,
      P  =  .001). CONCLUSIONS: Incoming intern perceptions on limiting duty hours
      vary. Many interns desire flexibility to exceed limits for interesting clinical
      opportunities and favor ACGME oversight. Clinical context matters when interns
      consider the tradeoffs between fatigue and discontinuity.

PMID- 22132275
TI  - The 4?1 schedule: a novel template for internal medicine residencies.
AB  - BACKGROUND: It is widely acknowledged that there is need for redesign of internal
      medicine training. Duty hour restrictions, an increasing focus on patient safety,
      the possibility of inadequate training in ambulatory care, and a growing shortage
      of primary care physicians are some factors that fuel this redesign movement.
      INTERVENTION: We implemented a 4?1 scheduling template that alternates
      traditional 4-week rotations with week-long ambulatory blocks. Annually, this
      provides 10 blocks of traditional rotations without continuity clinic sessions
      and 10 weeks of ambulatory experience without inpatient responsibilities. To
      ensure continuous resident presence in all areas, residents are divided into 5
      groups, each staggered by 1 week. EVALUATION: We surveyed residents and faculty
      before and after the intervention, with questions focused on attitudes toward
      ambulatory medicine and training. We also conducted focus groups with independent
      groups of residents and faculty, designed to assess the benefits and drawbacks of
      the new scheduling template and to identify areas for future improvement.
      RESULTS: Overall, the scheduling template minimized the conflicts between
      inpatient and outpatient training, promoted a stronger emphasis on ambulatory
      education, allowed for focused practice during traditional rotations, and
      enhanced perceptions of team development. By creating an immersion experience in
      ambulatory training, the template allowed up to 180 continuity clinic sessions
      during 3 years of training and provided improved educational continuity and
      continuity of patient care. CONCLUSION: Separating inpatient and ambulatory
      education allows for enhanced modeling of the evolving practice of internists and
      removes some of the conflict inherent in the present system.

PMID- 22132276
TI  - Improving residents' knowledge of arterial and central line placement with a web
      based curriculum.
AB  - BACKGROUND: Procedural skill is predicated on knowledge. We used a previously
      validated test to evaluate the impact of a web-based education program on medical
      residents' knowledge of 2 advanced medical procedures. METHODS: We enrolled 210
      internal medicine residents at 3 residency programs in a randomized, controlled,
      educational trial. Study participants completed a 20-item, validated online test
      of their knowledge of central venous and arterial line (CVL and AL, respectively)
      placement at baseline and after performing their next 2 procedures (test 1 and
      test 2). Between test 1 and test 2, participants were randomized to online
      educational material for CVL insertion, AL insertion, both, or neither. The
      primary outcome of the study was the difference in test scores between test 1 and
      test 2 by randomization group. RESULTS: Though residents in the baseline cohort
      were confident about their knowledge of procedural technique, their mean test
      scores were low (62% and 58% in the CVL and AL tests, respectively). Baseline
      test score correlated with the number of prior procedures performed. Sixty-five
      residents completed all 3 CVL tests, and 85 residents completed all 3 AL tests.
      Access to the web-based procedure education was associated with a significant
      improvement in scores for both the CVL test (effect size, d  =  0.25, P  =  .01)
      and AL test (d  =  0.52, P < .001). CONCLUSIONS: Web-based procedure training
      improves knowledge of procedures to a significantly greater extent than
      performing the procedure alone. Web-based curricula can effectively supplement
      other methods of skill development.

PMID- 22132277
TI  - Critical care education during internal medicine residency: a national survey.
AB  - BACKGROUND: Current training practices and teaching methods for critical care
      medicine education during internal medicine residency have not been well
      described. This study explored critical care medicine education practices and
      environments for internal medicine residents in the United States. METHODS: A web
      based survey recruited Pulmonary and Critical Care Medicine fellowship program
      directors involved with internal medicine residency programs at academic
      institutions in the United States. RESULTS: Of 127 accredited Pulmonary and
      Critical Care Medicine programs in 2007, 63 (50%) responded. Demographics of the
      intensive care units varied widely in size (7-52 beds), monthly admissions (25
      300 patients), and presence of a "night float" (22%) or an admissions "cap"
      (34%). All programs used bedside teaching, and the majority used informal
      sessions (91%) or didactic lectures (75%). More time was spent on resident
      teaching in larger (>=20 bed) medical intensive care units, on weekdays, in
      programs with a night-float system, and in programs that suspended residents'
      primary care clinic duties during their intensive care unit rotation.
      CONCLUSIONS: Although similar teaching methods were used within a wide range of
      training environments, there is no standardized approach to critical care
      medicine education for internal medicine residents. Some survey responses
      indicated a correlation with additional teaching time.

PMID- 22132278
TI  - An "education for life" requirement to promote lifelong learning in an internal
      medicine residency program.
AB  - BACKGROUND: Lifelong learning is an integral component of practice-based learning
      and improvement. Physicians need to be lifelong learners to provide timely,
      efficient, and state-of-the-art patient care in an environment where knowledge,
      technology, and social requirements are rapidly changing. OBJECTIVES: To assess
      graduates' self-reported perception of the usefulness of a residency program
      requirement to submit a narrative report describing their planned educational
      modalities for their future continued medical learning ("Education for Life"
      requirement), and to compare the modalities residents intended to use with their
      reported educational activities. MATERIALS AND METHODS: Data was compiled from
      the Education for Life reports submitted by internal medicine residents at the
      University of Tennessee College of Medicine Chattanooga from 1998 to 2000, and
      from a survey sent to the same 27 graduates 2 to 4 years later from 2000 to 2004.
      RESULTS: Twenty-four surveys (89%) were returned. Of the responding graduates,
      58% (14/24) found the Education for Life requirement useful for their future
      continued medical learning. Graduates intended to keep up with a mean of 3.4
      educational modalities, and they reported keeping up with 4.2. In a multivariable
      analysis, the number of modalities graduates used was significantly associated
      with the number they had planned to use before graduation (P  =  .04) but not
      with their career choice of subspecialization. CONCLUSION: The majority of
      residents found the Education for Life requirement useful for their future
      continued medical learning. Graduates, regardless of specialty, reported using
      more modalities for continuing their medical education than they thought they
      would as residents. Considering lifelong learning early in training and then
      requiring residents to identify ways to practice lifelong learning as a
      requirement for graduation may be dispositive.

PMID- 22132279
TI  - Automated data mining: an innovative and efficient web-based approach to
      maintaining resident case logs.
AB  - BACKGROUND: Use of resident case logs has been considered by the Residency Review
      Committee for Neurology of the Accreditation Council for Graduate Medical
      Education (ACGME). OBJECTIVE: This study explores the effectiveness of a data
      mining program for creating resident logs and compares the results to a manual
      data-entry system. Other potential applications of data mining to enhancing
      resident education are also explored. DESIGN/METHODS: Patient notes dictated by
      residents were extracted from the Hospital Information System and analyzed using
      an unstructured mining program. History, examination and ICD codes were obtained
      and compared to the existing manual log. The automated data History, examination,
      and ICD codes were gathered for a 30-day period and compared to manual case logs.
      RESULTS: The automated method extracted all resident dictations with the dates of
      encounter and transcription. The automated data-miner processed information from
      all 19 residents, while only 4 residents logged manually. The manual method
      identified only broad categories of diseases; the major categories were stroke or
      vascular disorder 53 (27.6%), epilepsy 28 (14.7%), and pain syndromes 26 (13.5%).
      In the automated method, epilepsy 114 (21.1%), cerebral atherosclerosis 114
      (21.1%), and headache 105 (19.4%) were the most frequent primary diagnoses, and
      headache 89 (16.5%), seizures 94 (17.4%), and low back pain 47 (9%) were the most
      common chief complaints. More detailed patient information such as tobacco use
      227 (42%), alcohol use 205 (38%), and drug use 38 (7%) were extracted by the data
      mining method. CONCLUSIONS: Manual case logs are time-consuming, provide limited
      information, and may be unpopular with residents. Data mining is a time-effective
      tool that may aid in the assessment of resident experience or the ACGME core
      competencies or in resident clinical research. More study of this method in
      larger numbers of residency programs is needed.

PMID- 22132280
TI  - Pediatric emergency medicine residency experience: requirements versus reality.
AB  - BACKGROUND: An important expectation of pediatric education is assessing,
      resuscitating, and stabilizing ill or injured children. OBJECTIVE: To determine
      whether the Accreditation Council for Graduate Medical Education (ACGME) minimum
      time requirement for emergency and acute illness experience is adequate to
      achieve the educational objectives set forth for categorical pediatric residents.
      We hypothesized that despite residents working five 1-month block rotations in a
      high-volume (95 000 pediatric visits per year) pediatric emergency department
      (ED), the comprehensive experience outlined by the ACGME would not be satisfied
      through clinical exposure. STUDY DESIGN: This was a retrospective, descriptive
      study comparing actual resident experience to the standard defined by the ACGME.
      The emergency medicine experience of 35 categorical pediatric residents was
      tracked including number of patients evaluated during training and patient
      discharge diagnoses. The achievability of the ACGME requirement was determined by
      reporting the percentage of pediatric residents that cared for at least 1 patient
      from each of the ACGME-required disorder categories. RESULTS: A total of 11.4% of
      residents met the ACGME requirement for emergency and acute illness experience in
      the ED. The median number of patients evaluated by residents during training in
      the ED was 941. Disorder categories evaluated least frequently included shock,
      sepsis, diabetic ketoacidosis, coma/altered mental status, cardiopulmonary
      arrest, burns, and bowel obstruction. CONCLUSION: Pediatric residents working in
      one of the busiest pediatric EDs in the country and working 1 month more than the
      ACGME-recommended minimum did not achieve the ACGME requirement for emergency and
      acute illness experience through direct patient care.

PMID- 22132282
TI  - Training intensivists and clinician-scientists for the 21st century: the Oregon
      scholars program.
AB  - BACKGROUND: Innovation is important for the development and advancement of any
      medical specialty. Leaders in anesthesiology have emphasized the need for more
      training in critical care and additional research to advance our specialty.
      INTERVENTION: To help address this need, Oregon Health & Science University
      (OHSU) developed an innovative training program that combines a critical care
      medicine (CCM) or research fellowship with traditional clinical anesthesia
      training. This article outlines the program structure, challenges, and successes
      of this innovative approach to training anesthesiology clinicians and scientists.
      FINDINGS: Since the program began in 2006, we have filled all available positions
      and currently have 9 scholars in the anesthesiology/CCM track and 3 in the
      anesthesiology/research track at the postgraduate year-2 to postgraduate year-5
      levels. Our first class of scholars graduated in the summer of 2010. The Oregon
      Scholars Program (OSP) scholars and faculty have confronted challenges, including
      the transition from resident in the operating rooms to fellow in the critical
      care units. In 2007, our residents acknowledged the OSP/CCM scholars' expertise
      in CCM and have looked to them as teachers and advocates for their education
      during their CCM rotations. In July 2007, OHSU received a National Institutes of
      Health T32 training grant to support the research component of the OSP. OSP
      scholars' research productivity has resulted in 11 publications, 3 abstracts, 3
      presentations, 3 research grants, and 1 resident research award. Several other
      anesthesiology programs have recently instituted similar programs to address the
      need for anesthesiologists trained as intensivists and clinician-scientists.

PMID- 22132281
TI  - Pediatrics milestone project: next steps toward meaningful outcomes assessment.
AB  - In the September 2010 issue of JGME, the Pediatric Milestones Working Group
      published "The Pediatrics Milestones: Conceptual Framework, Guiding Principles,
      and Approach to Development", a document that describes the construction of the
      first iteration of the Pediatric Milestones. These Milestones were developed by
      the Working Group as a group of practical behavioral expectations for each of the
      52 sub-competencies. In constructing these Milestones, the authors were cognizant
      of the need to ground the Milestones themselves in evidence, theories or other
      conceptual frameworks that would provide the basis for the ontogeny of
      development for each sub-competency. During this next phase of the Milestones
      development, the process will continue with consultation with content experts and
      consideration of assessment of Milestones. We have described possible measurement
      tools, explored threats to validity, establishment of benchmarks, and possible
      approaches to reporting of performance. The vision of the Pediatrics Milestone
      Project is to understand the development of a pediatrician from entry into
      medical school through the twilight of a physician's career, and the work will
      require a collaborative effort of the undergraduate and graduate medical
      education communities, and the accrediting and certifying bodies.

PMID- 22132283
TI  - Teaching Risk Management: Addressing ACGME Core Competencies.
AB  - BACKGROUND: Risk management is an important aspect of education for all
      residents. Unfortunately, few curricula currently exist to fulfill this
      educational need. OBJECTIVE: We developed a curriculum that teaches residents
      basic principles of risk management with the goals of (1) educating residents
      about the medical-legal environment in which they operate, (2) helping residents
      identify common malpractice exposures, and (3) teaching practical risk
      management/patient safety interventions that can be implemented in their practice
      that could reduce malpractice exposure and improve patient safety. METHODS: The
      curriculum was developed by Medical Risk Management, LLC, a Connecticut-based
      risk management firm, in conjunction with academic leadership at the University
      of Connecticut. The program uses 3 learning modalities: live lectures, web-based
      video modules, and e-mailed learning publications. Gains in resident knowledge
      through participation in the curriculum were measured using pretests and
      posttests. Learner satisfaction with the curriculum was measured through web
      based surveys. RESULTS: We found a significant improvement in knowledge in
      residents who took the pretest and posttest (P < .001). Of the survey
      respondents, 97% said the content was relevant to their specialty practice and
      95% responded that these sessions should be held annually. Most respondents
      indicated they would change their practice as a result of what they learned from
      the live lectures. CONCLUSION: This risk management curriculum has been
      successful in providing our residents with learning activities in risk
      management, improving their knowledge of risk management principles, and changing
      their attitudes and behaviors. These improvements may lead to fewer malpractice
      claims against them and the hospitals they train in.

PMID- 22132284
TI  - Medico-legal education: a pilot curriculum to fill the identified knowledge gap.
AB  - PURPOSE: We sought to determine if a medico-legal educational curriculum designed
      to increase physicians' familiarity with the legal system in a nonthreatening
      environment-a didactic and interactive educational seminar-would positively
      influence learners' knowledge base and self-awareness. METHODS: Because neither
      the Accreditation Council for Graduate Medical Education nor its Residency Review
      Committees specifically addresses medico-legal liability education, we designed a
      2-day intensive medico-legal educational curriculum and piloted it in 2007 and
      2008 at a large academic tertiary-referral medical center. Postcurriculum
      evaluations and precurriculum and postcurriculum testing were used to identify
      areas of common and/or persisting knowledge deficit. RESULTS: A total of 50
      graduating residents, fellows, and community practitioners participated in the
      course. Common areas of knowledge deficit were "privilege," "discovery," statutes
      of limitations, and basic legal procedure. Discordance in physician
      interpretation of patient perspective and misunderstanding among physicians of
      the impact of the legal suit were evident. CONCLUSIONS: Concentrated legal
      education at selected times during medical training may support physicians'
      motivations to improve the assurance of quality and continuity of care. We
      continue to revise the curriculum to address issues of lecturer style, lecture
      content, and overall attitudinal values related to clinical practice, legal
      education, long-term impact on practice patterns, job satisfaction and its effect
      on attention to quality and continuity-of-care issues, and health care provider
      attitudes about the provider's role within the legal system and the community. We
      plan to conduct follow-up of participants to assess retention and subsequent use
      of this knowledge.

PMID- 22132285
TI  - Relationship express: a pilot program to teach anesthesiology residents
      communication skills.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education requires
      residency programs to teach 6 core competencies and to provide evidence of
      effective standardized training through objective measures. George Washington
      University's Department of Anesthesiology and Critical Care Medicine implemented
      a pilot program to address the interpersonal and communication skill competency.
      In this program, we aimed to pilot the Relationship Express model, a series of
      exercises in experiential learning to teach anesthesiology residents to build
      effective relationships with patients in time-limited circumstances. The purpose
      of this paper is to describe the application of this model for anesthesiology
      training. METHODS: A total of 7 first-year clinical anesthesiology residents
      participated in this pilot study, and 4 residents completed the entire program
      for analysis purposes. Relationship Express was presented in three 1.5-hour
      sessions: (1) introduction followed by 2-case, standardized patient pretest with
      feedback to residents from faculty observers; (2) interpersonal and communication
      skills didactic workshop with video behavior modeling; and (3) review discussion
      followed by 2-case, standardized patient posttest and evaluation. RESULTS:
      MODIFIED BROOKFIELD COMMENTS REVEALED THE FOLLOWING THEMES: (1) time constraints
      were realistic compared with clinical practice; (2) admitting errors with
      patients was difficult; (3) patients were more aware of body language than
      anticipated; (4) residents liked the group discussions and the video interview;
      (5) standardized patients were convincing; and (6) residents found the feedback
      from faculty and standardized patients helpful. CONCLUSIONS: Resident
      retrospective self-assessment and learning comments confirm the potential value
      of the Relationship Express model. This program will require further assessment
      and refinement with a larger number of residents.

PMID- 22132286
TI  - Internal reviews benefit programs of the review team members and the program
      under review.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      mandates that sponsoring institutions conduct internal reviews. In 1998, the
      ACGME Institutional Review Committee gave Duke University Hospital a citation for
      an inadequate internal review (IR) process. Since then, we have instituted
      several iterative changes. We describe the evolution of Duke University
      Hospital's current internal review process. INTERVENTION: We implemented a new
      review team composition, template report, use of the program information form,
      and centralization of documentation to improve our internal review process. In
      2007, a more formal evaluation of the outcome and impact of these changes was
      instituted. This included a yearly survey of all participants and review team
      members, a review of programs, and a tracking process for the decisions of our
      Graduate Medical Education Committee (GMEC) on the status of reviewed programs.
      RESULTS: Participants from both the program under review and the review team
      evaluated the process favorably. Review teams reported they learned from the best
      practices of the program being reviewed. Program directors from the reviewed
      programs reported the process improved their documentation. Both groups reported
      the process better prepared them for their next ACGME Review Committee site
      visit. The GMEC has recommended "probationary sponsorship" for fewer programs
      since the IR process changes have been implemented. The IR process was recognized
      as a best practice in Duke University Hospital's 2004 ACGME institutional review.
      CONCLUSION: We believe our IR process, review-team composition, template report,
      program information form, and centralized documentation now fully meets
      accreditation standards. Participants are reasonably satisfied and report value
      from the process. More programs are judged to be within substantial compliance by
      the GMEC.

PMID- 22132287
TI  - No time to think: making room for reflection in obstetrics and gynecology
      residency.
AB  - BACKGROUND: Reflective practice may help physicians identify and connect with
      what they value and find meaningful in their work. There are many practical
      obstacles in teaching narrative skills and reflection to residents in surgical
      subspecialties. We aimed to assess the feasibility of designing and implementing
      a writing workshop series within an obstetrics and gynecology curriculum.
      MATERIALS AND METHODS: Between 2008 and 2009, a reflective writing workshop
      series was introduced into the didactic curriculum of an obstetrics and
      gynecology residency program. The course included reading fiction and creative
      writing. Workshops focused on topics residents identified. Residents answered a
      subjective questionnaire and also completed the Maslach Burnout Inventory and
      Interpersonal Reactivity Index to assess burnout and empathy. RESULTS: Six 1-hour
      reflective writing workshops took place within the dedicated didactic time for
      residents. Of the 20 residents in the program, 10 junior residents and 8 senior
      residents evaluated the workshops. Ten residents participated in more than one
      workshop, an average of 3.6 workshops. Residents felt that the workshops were
      enjoyable, and some felt that they influenced their experience of residency, but
      few felt that it affected their work with patients. Trends in Maslach Burnout
      Inventory and Interpersonal Reactivity Index scores did not show statistical
      significance. CONCLUSION: A practical curriculum for introducing reflective
      practice to obstetrics and gynecology residents is described. This model may be
      useful to educators looking to incorporate reflective practice into residency
      curricula and lead to collaborative work that may assess the impact of this work
      on the experience of residents and their patients.

PMID- 22132288
TI  - Tracking Residents Through Multiple Residency Programs: A Different Approach for
      Measuring Residents' Rates of Continuing Graduate Medical Education in ACGME
      Accredited Programs.
AB  - BACKGROUND: Increased focus on the number and type of physicians delivering
      health care in the United States necessitates a better understanding of changes
      in graduate medical education (GME). Data collected by the Accreditation Council
      for Graduate Medical Education (ACGME) allow longitudinal tracking of residents,
      revealing the number and type of residents who continue GME following completion
      of an initial residency. We examined trends in the percent of graduates pursuing
      additional clinical education following graduation from ACGME-accredited pipeline
      specialty programs (specialties leading to initial board certification). METHODS:
      Using data collected annually by the ACGME, we tracked residents graduating from
      ACGME-accredited pipeline specialty programs between academic year (AY) 2002-2003
      and AY 2006-2007 and those pursuing additional ACGME-accredited training within 2
      years. We examined changes in the number of graduates and the percent of
      graduates continuing GME by specialty, by type of medical school, and overall.
      RESULTS: The number of pipeline specialty graduates increased by 1171 (5.3%)
      between AY 2002-2003 and AY 2006-2007. During the same period, the number of
      graduates pursuing additional GME increased by 1059 (16.7%). The overall rate of
      continuing GME increased each year, from 28.5% (6331/22229) in AY 2002-2003 to
      31.6% (7390/23400) in AY 2006-2007. Rates differed by specialty and for US
      medical school graduates (26.4% [3896/14752] in AY 2002-2003 to 31.6%
      [4718/14941] in AY 2006-2007) versus international medical graduates (35.2%
      [2118/6023] to 33.8% [2246/6647]). CONCLUSION: The number of graduates and the
      rate of continuing GME increased from AY 2002-2003 to AY 2006-2007. Our findings
      show a recent increase in the rate of continued training for US medical school
      graduates compared to international medical graduates. Our results differ from
      previously reported rates of subspecialization in the literature. Tracking
      individual residents through residency and fellowship programs provides a better
      understanding of residents' pathways to practice.

PMID- 22132289
TI  - Curriculum providing cognitive knowledge and problem-solving skills for
      anesthesia systems-based practice.
AB  - BACKGROUND: Residency programs accredited by the ACGME are required to teach core
      competencies, including systems-based practice (SBP). Projects are important for
      satisfying this competency, but the level of knowledge and problem-solving skills
      required presupposes a basic understanding of the field. The responsibilities of
      anesthesiologists include the coordination of patient flow in the surgical suite.
      Familiarity with this topic is crucial for many improvement projects.
      INTERVENTION: A course in operations research for surgical services was
      originally developed for hospital administration students. It satisfies 2 of the
      Institute of Medicine's core competencies for health professionals: evidence
      based practice and work in interdisciplinary teams. The course lasts 3.5 days
      (eg, 2 weekends) and consists of 45 cognitive objectives taught using 7 published
      articles, 10 lectures, and 156 computer-assisted problem-solving exercises based
      on 17 case studies. We tested the hypothesis that the cognitive objectives of the
      curriculum provide the knowledge and problem-solving skills necessary to perform
      projects that satisfy the SBP competency. Standardized terminology was used to
      define each component of the SBP competency for the minimum level of knowledge
      needed. The 8 components of the competency were examined independently. FINDINGS:
      Most cognitive objectives contributed to at least 4 of the 8 core components of
      the SBP competency. Each component of SBP is addressed at the minimum requirement
      level of exemplify by at least 6 objectives. There is at least 1 cognitive
      objective at the level of summarize for each SBP component. CONCLUSIONS: A
      curriculum in operating room management can provide the knowledge and problem
      solving skills anesthesiologists need for participation in projects that satisfy
      the SBP competency.

PMID- 22132290
TI  - Practice-based learning and improvement for institutions: a case report.
AB  - BACKGROUND: In 2006, the University of Virginia became one of the first academic
      medical institutions to be placed on probation, after the Accreditation Council
      for Graduate Medical Education (ACGME) Institutional Review Committee implemented
      a new classification system for institutional reviews. INTERVENTION: After
      University of Virginia reviewed its practices and implemented needed changes, the
      institution was able to have probation removed and full accreditation restored.
      Whereas graduate medical education committees and designated institutional
      officials are required to conduct internal reviews of each ACGME-accredited
      program midway through its accreditation cycle, no similar requirement exists for
      institutions. LEARNING: As we designed corrective measures at the University of
      Virginia, we realized that regularly scheduled audits of the entire institution
      would have prevented the accumulation of deficiencies. We suggest that
      institutional internal reviews be implemented to ensure that the ACGME
      institutional requirements for graduate medical education are met. This process
      represents practice-based learning and improvement at the institutional level and
      may prevent other institutions from receiving unfavorable accreditation
      decisions.

PMID- 22132292
TI  - Expertise, Diversity, and Perspective: Introducing the JGME Editorial Board.

PMID- 22132293
TI  - Residency as Identity Transformation: The Life Stages of the Homo medicalis.

PMID- 22132291
TI  - Evaluating practice-based learning and improvement: efforts to improve acceptance
      of portfolios.
AB  - INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME)
      recommends resident portfolios as 1 method for assessing competence in practice
      based learning and improvement. In July 2005, when anesthesiology residents in
      our department were required to start a portfolio, the residents and their
      faculty advisors did not readily accept this new requirement. Intensive education
      efforts addressing the goals and importance of portfolios were undertaken. We
      hypothesized that these educational efforts improved acceptance of the portfolio
      and retrospectively audited the portfolio evaluation forms completed by faculty
      advisors. METHODS: Intensive education about the goals and importance of
      portfolios began in January 2006, including presentations at departmental
      conferences and one-on-one education sessions. Faculty advisors were instructed
      to evaluate each resident's portfolio and complete a review form. We
      retrospectively collected data to determine the percentage of review forms
      completed by faculty. The portfolio reviews also assessed the percentage of 10
      required portfolio components residents had completed. RESULTS: Portfolio review
      forms were completed by faculty advisors for 13% (5/38) of residents during the
      first advisor-advisee meeting in December 2005. Initiation of intensive education
      efforts significantly improved compliance, with review forms completed for 68%
      (26/38) of residents in May 2006 (P < .0001) and 95% (36/38) in December 2006 (P
      < .0001). Residents also significantly improved the completeness of portfolios
      between May and December of 2006. DISCUSSION: Portfolios are considered a best
      methods technique by the ACGME for evaluation of practice-based learning and
      improvment. We have found that intensive education about the goals and importance
      of portfolios can enhance acceptance of this evaluation tool, resulting in
      improved compliance in completion and evaluation of portfolios.

PMID- 22132294
TI  - Residency Programs' Evaluations of the Competencies: Data Provided to the ACGME
      About Types of Assessments Used by Programs.
AB  - BACKGROUND: In 1999, the Accreditation Council for Graduate Medical Education
      (ACGME) Outcome Project began to focus on resident performance in the 6
      competencies of patient care, medical knowledge, professionalism, practice-based
      learning and improvement, interpersonal communication skills, and
      professionalism. Beginning in 2007, the ACGME began collecting information on how
      programs assess these competencies. This report provides information on the
      nature and extent of those assessments. METHODS: Using data collected by the
      ACGME for site visits, we use descriptive statistics and percentages to describe
      the number and type of methods and assessors accredited programs (n  =  4417)
      report using to assess the competencies. Observed differences among specialties,
      methodologies, and assessors are tested with analysis of variance procedures.
      RESULTS: Almost all (>97%) of programs report assessing all of the competencies
      and using multiple methods and multiple assessors. Similar assessment methods and
      evaluator types were consistently used across the 6 competencies. However, there
      were some differences in the use of patient and family as assessors: Primary care
      and ambulatory specialties used these to a greater extent than other specialties.
      CONCLUSION: Residency programs are emphasizing the competencies in their
      evaluation of residents. Understanding the scope of evaluation methodologies that
      programs use in resident assessment is important for both the profession and the
      public, so that together we may monitor continuing improvement in US graduate
      medical education.

PMID- 22132295
TI  - Changes in resident work and sleep hours 1999 to 2009: results from a survey of 4
      specialties.

PMID- 22132296
TI  - Current status of low dose multi-detector CT in the urinary tract.
AB  - Over the past several years, advances in the technical domain of computed
      tomography (CT) have influenced the trend of imaging modalities used in the
      clinical evaluation of the urinary system. Renal collecting systems can be
      illustrated more precisely with the advent of multi-detector row CT through
      thinner slices, high speed acquisitions, and enhanced longitudinal spatial
      resolution resulting in improved reformatted coronal images. On the other hand, a
      significant increase in exposure to ionizing radiation, especially in the
      radiosensitive organs, such as the gonads, is a concern with the increased
      utilization of urinary tract CT. In this article, we discuss the strategies and
      techniques available for reducing radiation dose for a variety of urinary tract
      CT protocols with metabolic clinical examples. We also reviewed CT for hematuria
      evaluation and related scan parameter optimization such as, reducing the number
      of acquisition phases, CT angiography of renal donors and lowering tube
      potential, when possible.

PMID- 22132297
TI  - Magnetic resonance imaging appearance and changes on intracavitary Gliadel wafer
      placement: A pilot study.
AB  - AIM: To investigate changes on magnetic resonance imaging (MRI) which occur with
      intracavitary Gliadel wafer placement in patients with glioblastoma multiforme
      (GBM). METHODS: This retrospective Health Insurance Portability and
      Accountability Act-compliant study was approved by the institutional review
      board, with a waiver of informed consent. A total of eight patients aged 29-67
      years with GBM underwent Gliadel wafer placement. T2-weighted/FLAIR images and
      post-contrast T1-weighted images both before and after wafer placement were
      retrospectively reviewed in consensus to determine changes in the following
      parameters: appearance of the pericavitary tissue, pattern of tumor recurrence or
      progression and appearance of the Gliadel wafer itself. RESULTS: Five out of the
      eight patients had a progressive increase in enhancement and pericavitary T2/
      FLAIR hyperintensity within the first 2 mo and a subsequent decrease in these MRI
      findings. None of these patients had tumor recurrence within the first 6 mo.
      Three out of the eight patients demonstrated a progressive increase in
      enhancement and pericavitary T2 hyperintensity, which continued after the first 6
      mo, and were subsequently diagnosed with true tumor progression. There was no
      increase in distant/nonlocal tumor recurrence. The Gliadel wafer appearance
      changed over time. CONCLUSION: Pseudoprogression is common after intracavitary
      Gliadel wafer placement and thus care should be taken before diagnosing tumor
      progression or recurrence within the first 2 mo.

PMID- 22132299
TI  - Ordered arrays of multiferroic epitaxial nanostructures.
AB  - Epitaxial heterostructures combining ferroelectric (FE) and ferromagnetic (FiM)
      oxides are a possible route to explore coupling mechanisms between the two
      independent order parameters, polarization and magnetization of the component
      phases. We report on the fabrication and properties of arrays of hybrid epitaxial
      nanostructures of FiM NiFe(2)O(4) (NFO) and FE PbZr(0.52)Ti(0.48)O(3) or
      PbZr(0.2)Ti(0.8)O(3), with large range order and lateral dimensions from 200 nm
      to 1 micron. METHODS: The structures were fabricated by pulsed-laser deposition.
      High resolution transmission electron microscopy and high angle annular dark
      field scanning transmission electron microscopy were employed to investigate the
      microstructure and the epitaxial growth of the structures. Room temperature
      ferroelectric and ferrimagnetic domains of the heterostructures were imaged by
      piezoresponse force microscopy (PFM) and magnetic force microscopy (MFM),
      respectively. RESULTS: PFM and MFM investigations proved that the hybrid
      epitaxial nanostructures show ferroelectric and magnetic order at room
      temperature. Dielectric effects occurring after repeated switching of the
      polarization in large planar capacitors, comprising ferrimagnetic NiFe2O4 dots
      embedded in ferroelectric PbZr0.52Ti0.48O3 matrix, were studied. CONCLUSION:
      These hybrid multiferroic structures with clean and well defined epitaxial
      interfaces hold promise for reliable investigations of magnetoelectric coupling
      between the ferrimagnetic / magnetostrictive and ferroelectric / piezoelectric
      phases.

PMID- 22132298
TI  - Digital radiography of crush thoracic trauma in the Sichuan earthquake.
AB  - AIM: To investigate the features of crush thoracic trauma in Sichuan earthquake
      victims using chest digital radiography (CDR). METHODS: We retrospectively
      reviewed 772 CDR of 417 females and 355 males who had suffered crush thoracic
      trauma in the Sichuan earthquake. Patient age ranged from 0.5 to 103 years. CDR
      was performed between May 12, 2008 and June 7, 2008. We looked for injury to the
      thoracic cage, pulmonary parenchyma and the pleura. RESULTS: Antero-posterior
      (AP) and lateral CDR were obtained in 349 patients, the remaining 423 patients
      underwent only AP CDR. Thoracic cage fractures, pulmonary contusion and pleural
      injuries were noted in 331 (42.9%; 95% CI: 39.4%-46.4%), 67 and 135 patients,
      respectively. Of the 256 patients with rib fractures, the mean number of
      fractured ribs per patient was 3. Rib fractures were mostly distributed from the
      3rd through to the 8th ribs and the vast majority involved posterior and lateral
      locations along the rib. Rib fractures had a significant positive association
      with non-rib thoracic fractures, pulmonary contusion and pleural injuries (P <
      0.001). The number of rib fractures and pulmonary contusions were significant
      factors associated with patient death. CONCLUSION: Earthquake-related crush
      thoracic trauma has the potential for multiple fractures. The high number of
      fractured ribs and pulmonary contusions were significant factors which needed
      appropriate medical treatment.

PMID- 22132300
TI  - Single-molecule photochemical reactions of Auger-ionized quantum dots.
AB  - Photoinduced electron transfer in donor-acceptor systems composed of quantum dots
      (QDs) and electron donors or acceptors is a subject of considerable recent
      research interest due to the potential applications of such systems in both solar
      energy harvesting and degradation of organic pollutants. Herein, we employed
      single-molecule imaging and spectroscopy techniques for the detection of
      photochemical reactions between 1,4-diaminobutane (DAB) and CdSe/ZnS single QDs.
      We investigated the reactions by analyzing photoluminescence (PL) intensity and
      lifetime of QDs at ensemble and single-molecule levels. While DAB was applied to
      single QDs tethered on a cover slip or QDs dispersed in a solution, PL intensity
      of QD continuously decreased with a concomitant increase in the PL lifetime.
      Interestingly, these changes in the PL properties of QD were predominant under
      high-intensity photoactivation. We hypothesize that the above changes in the PL
      properties surface due to the transfer of an electron from DAB to Auger-ionized
      QD followed by elimination of a proton from DAB and the formation of a QD-DAB
      adduct. Thus, a continuous decrease in the PL intensity of QDs under high
      intensity photoactivation is attributed to continuous photochemical reactions of
      DAB with single QDs and the formation of QD-(DAB)(n) adducts. We believe that
      detection and analysis of such photochemical reactions of single QDs with amines
      will be of considerable broad interest due to the significant impact of
      photoinduced electron transfer reactions in energy management and environmental
      remediation.

PMID- 22132301
TI  - Improving islet engraftment by gene therapy.
AB  - Islet cell transplantation is currently the only feasible long-term treatment
      option for patients with type 1 diabetes. However, the majority of transplanted
      islets experience damage and apoptosis during the isolation process, a blood
      mediated inflammatory microenvironment in the portal vein upon islet infusion,
      hypoxia induced by the low oxygenated milieu, and poor-revascularization-mediated
      lack of nutrients, and impaired hormone modulation in the local transplanted
      site. Strategies using genetic modification methods through overexpression or
      silencing of those proteins involved in promoting new formation of blood vessels
      or inhibition of apoptosis may overcome these hurdles and improve islet
      engraftment outcomes.

PMID- 22132303
TI  - Estimation of Abbreviated Cyclosporine A Area under the Concentration-Time Curve
      in Allogenic Stem Cell Transplantation after Oral Administration.
AB  - Measurements of Cyclosporine (CsA) systemic exposure permit its dose adjustment
      in allogenic stem cell transplantation recipients to prevent graft-versus-host
      disease. CsA LSSs were developed and validated from 60 ASCT patients via multiple
      linear regressions. All whole-blood samples were analyzed by fluorescence
      polarization immunoassay (FPIA-Axym). The 10 models that have used CsA
      concentrations at a single time point did not have a good fit with AUC(0-12)
      (R(2) < 0.90). C(2) and C(4) were the time points that correlated best with AUC(0
      12 h), R(2) were respectively 0.848, and 0.897. The LSS equation with the best
      predictive performance (bias, precision and number of samples) utilized three
      sampling concentrations was AUC(0-12 h) = 0.607 + 1.569 * C(0.5) + 2.098 * C(2) +
      3.603 * C(4) (R(2) = 0.943). Optimal LSSs equations which limited to those
      utilizing three timed concentrations taken within 4 hours post-dose developed
      from ASCT recipient's patients yielded a low bias <5% ranged from 1.27% to 2.68%
      and good precision <15% ranged from 9.60% and 11.02%. We propose an LSS model
      with equation AUC(0-12 h) = 0.82 + 2.766 * C(2) + 3.409 * C(4) for a practical
      reason. Bias and precision for this model are respectively 2.68% and 11.02%.

PMID- 22132302
TI  - Use of cyclosporine in uterine transplantation.
AB  - Uterine transplantation has been proposed as a possible solution to absolute
      uterine factor infertility untreatable by any other option. Since the first human
      attempt in 2000, various teams have tried to clarify which immunosuppressant
      would be most suitable for protecting the allogeneic uterine graft while posing a
      minimal risk to the fetus. Cyclosporine A (CsA) is an immunosuppressant widely
      used by transplant recipients. It is currently being tested as a potential
      immunosuppressant to be used during UTn. Its effect on the mother and fetus and
      its influence upon the graft during pregnancy have been of major concern. We
      review the role of CsA in UTn and its effect on pregnant transplant recipients
      and their offspring.

PMID- 22132304
TI  - Molecular Identification of Enterocytozoon bieneusi Isolates from Nigerian
      Children.
AB  - A study was conducted to detect and identify enteric microsporidian species in 43
      children from Oyo state, Nigeria. Using nested polymerase chain reaction, 9.3% of
      the children were identified as positive for Enterocytozoon bieneusi. DNA
      sequencing of the PCR products showed the presence of three known genotypes (two
      isolates of genotype D and one of genotype K) and one new genotype. This study
      suggests that either human or animal (or both) could be the infection source for
      the children, since identified genotypes D and K have been previously detected in
      both immunocompromised and immunocompetent patients and domestic animals. The
      identification of high diversity also suggests intensive transmission of
      microsporidiosis in the studied area.

PMID- 22132305
TI  - Studies on Fungal Cultural Filtrates against Adult Culex quinquefasciatus
      (Diptera: Culicidae) a Vector of Filariasis.
AB  - Entomopathogenic fungi have significant potential to control mosquito population.
      The culture filtrates of Fusarium oxysporum, Lagenidium giganteum, Trichophyton
      ajelloi, and Culicinomyces clavisporus were evaluated against adults of Cx.
      quinquefasciatus. The culture filtrates were obtained by filtering the broth
      through Whatman-1 filter paper. These culture filtrates of C. clavisporus have
      been found significantly pathogenic with LC(50)-2.5, LC(90)-7.24, and LC(99)-8.7
      ML, respectively, after exposure of 24 h. However, the culture filtrates when
      were combined, in ratios 1 : 1 : 1 of Fusarium oxysporum, Lagenidium giganteum,
      Trichophyton ajelloi the mortalities were significantly increased. The LC(50)
      3.71, LC(90)-8.12, and LC(99)-11.48 were significantly recorded after exposure of
      10 hrs. Similarly, the culture filtrates of T. ajelloi, Culicinomyces
      clavisporus, and L. giganteum have been combined in ratios 1 : 1 : 1. Similarly
      the LC(50)-1.94, LC(90)-4, and LC(99)-6.16 ML Were recorded after exposure of 10
      hrs. The results of present study show promise for the use of selected fungal
      metabolites for control of Cx. quinquefasciatus in the Laboratory.

PMID- 22132306
TI  - Fascioliasis control: in vivo and in vitro phytotherapy of vector snail to kill
      fasciola larva.
AB  - Snail is one of the important components of an aquatic ecosystem, it acts as
      intermediate host of Fasciola species. Control of snail population below a
      certain threshold level is one of the important methods in the campaign to reduce
      the incidence of fascioliasis. Life cycle of the parasite can be interrupted by
      killing the snail or Fasciola larva redia and cercaria in the snail body. In vivo
      and in vitro toxicity of the plant products and their active component such as
      citral, ferulic acid, umbelliferone, azadirachtin, and allicin against larva of
      Fasciola in infected snail Lymnaea acuminata were tested. Mortality of larvae
      were observed at 2 h, 4 h, 6 h, and 8 h, of treatment. In in vivo treatment,
      azadirachtin caused highest mortality in redia and cercaria larva (8 h, LC(50)
      0.11, and 0.05 mg/L) whereas in in vitro condition allicin was highly toxic
      against redia and cercaria (8 h, LC(50) 0.01, and 0.009 mg/L). Toxicity of citral
      was lowest against redia and cercaria larva.

PMID- 22132307
TI  - Indian schistosomes: a need for further investigations.
AB  - India is uniquely positioned with regard to schistosomes and schistosomiasis
      discovering seven new mammalian species with the existence of three more
      schistosome species: Orientobilharzia turkestanicum, O. harinasutai, and
      Schistosoma haematobium(?). An endemic focus of urinary schistosomiasis was
      reported from Gimvi village of Ratnagiri, Maharashtra with infrequent occurrence
      of schistosome eggs in human stools. Cercarial dermatitis has been reported to be
      more abundant in rural population using ponds, tanks, and so forth, for their
      domestic purposes. Few dermatitis cases were tested positive by CHR. Schistosome
      antigen was also detected in urine of five cases suggesting existence of active
      schistosomiasis in India. Nevertheless, human kind does not appear to be the
      usual host for Indian schistosomes in contrast to S. haematobium, S. mansoni, or
      S. japonicum. Various reasons for this phenomenon are discussed including
      evolution of Indian schistosomes, immune mechanisms, and environmental
      conditions. These and other aspects such as seasonal effect on the prevalence,
      snail infectivity, heterologous mating, existence of hybrids, and number of
      schistosomes in heterologous infections need further investigations with
      application of molecular techniques. Joint efforts by the national as well as
      international scientific community would be much more rewarding for better
      understanding of the parasite and the infection.

PMID- 22132308
TI  - Short communication: evaluation of a new rapid diagnostic test for quality
      assurance by kala azar elimination programme in bangladesh.
AB  - In Bangladesh, serological tests have been widely used for the primary screening
      of visceral leishmaniasis (VL). Several serologic tests are available for the
      diagnosis of VL. Selection of the best test is important to permit diagnostic
      differentiation between symptomatic and asymptomatic patients and to reduce cross
      reactivity. We evaluated the effectiveness of a new serological test "Onsite
      Leishmania Ab Rapid Test" as a part of "quality assurance" activities for the
      kala azar elimination programme of the Government of Bangladesh. Plasma samples
      of 100 parasitologically confirmed cases of VL along with 101 healthy controls
      were tested, and "Onsite Leishmania Ab Rapid Test" strip tests were positive in
      94 out of 100 confirmed VL cases, whereas four out of 51 healthy subjects from
      the VL endemic areas also tested positive. All the 50 healthy volunteers tested
      negative. Thus, the sensitivity and specificity of "Onsite Leishmania Ab Rapid
      Test" strip test were found to be 94% (95% CI: 87-98) and 96% (95% CI: 90-99),
      respectively. This study showed that the performance of the "Onsite Leishmania Ab
      Rapid Test" strip tests was up to the recommended level.

PMID- 22132310
TI  - Minimizing surgically induced astigmatism at the time of cataract surgery using a
      square posterior limbal incision.
AB  - Purpose. To compare the surgically induced astigmatism from clear corneal and
      square posterior limbal incisions at the time of cataract surgery. Methods.
      Surgically induced astigmatism was calculated for a set of eyes after cataract
      surgery using a temporal 2.2 mm square posterior limbal incision. Results were
      compared to similar available data from surgeons using clear corneal incisions of
      similar size. Results. Preoperative corneal astigmatism averaged 1.0 D and was
      not significantly different between the incision types. Surgically induced
      astigmatism with the 2.2 mm posterior limbal incision averaged 0.25 +/- 0.14 D,
      significantly lower in magnitude than the aggregate surgically induced
      astigmatism produced by the 2.2 mm clear corneal incision (0.68 +/- 0.49 D).
      Conclusion. The 2.2 mm square posterior limbal incision induced significantly
      less, and significantly less variable, surgically induced astigmatism relative to
      a similar-sized clear corneal incision. This is likely to improve refractive
      outcomes, particularly important with regard to premium intraocular lenses.

PMID- 22132309
TI  - Lysophosphatidylcholine: A Novel Modulator of Trypanosoma cruzi Transmission.
AB  - Lysophosphatidylcholine is a bioactive lipid that regulates a large number of
      cellular processes and is especially present during the deposition and
      infiltration of inflammatory cells and deposition of atheromatous plaque. Such
      molecule is also present in saliva and feces of the hematophagous organism
      Rhodnius prolixus, a triatominae bug vector of Chagas disease. We have recently
      demonstrated that LPC is a modulator of Trypanosoma cruzi transmission. It acts
      as a powerful chemoattractant for inflammatory cells at the site of the insect
      bite, which will provide a concentrated population of cells available for
      parasite infection. Also, LPC increases macrophage intracellular calcium
      concentrations that ultimately enhance parasite invasion. Finally, LPC inhibits
      NO production by macrophages stimulated by live T. cruzi, and thus interferes
      with the immune system of the vertebrate host. In the present paper, we discuss
      the main signaling mechanisms that are likely used by such molecule and their
      eventual use as targets to block parasite transmission and the pathogenesis of
      Chagas disease.

PMID- 22132312
TI  - Retrobulbar hemodynamic effects of nipradilol in normal and normal-tension
      glaucoma eyes.
AB  - Purpose. To investigate the effects of nipradilol on retrobulbar hemodynamics.
      Methods. We investigated normal and normal-tension glaucoma (NTG) eyes. Topical
      nipradilol (one eye) and placebo eye drops (fellow eye) were instilled for 1 week
      in volunteers. Nipradilol was also instilled in NTG patients. Ultrasound color
      Doppler imaging for the posterior vessels was performed before, 2 hr, 1 week (for
      normal), and at 4 weeks (for NTG). Results. In normal eyes, there were
      significant decreases in the resistance index (RI) for the temporal short
      posterior ciliary arteries (PCA) at 2 hr and for the ophthalmic arteries at 1
      week. There were no significant changes in the placebo-treated eyes. In the NTG
      eyes, there was a significant decrease in the RI for the central retinal artery,
      nasal, and temporal PCA at 2 hr and 4 weeks. Conclusion. Short-term observations
      found that nipradilol increased the ocular blood flow in normal and NTG eyes.

PMID- 22132313
TI  - Simultaneous confocal scanning laser ophthalmoscopy combined with high-resolution
      spectral-domain optical coherence tomography: a review.
AB  - We aimed to evaluate technical aspects and the clinical relevance of a
      simultaneous confocal scanning laser ophthalmoscope and a high-speed, high
      resolution, spectral-domain optical coherence tomography (SDOCT) device for
      retinal imaging. The principle of confocal scanning laser imaging provides a high
      resolution of retinal and choroidal vasculature with low light exposure. Enhanced
      contrast, details, and image sharpness are generated using confocality. The real
      time SDOCT provides a new level of accuracy for assessment of the angiographic
      and morphological correlation. The combined system allows for simultaneous
      recordings of topographic and tomographic images with accurate correlation
      between them. Also it can provide simultaneous multimodal imaging of retinal
      pathologies, such as fluorescein and indocyanine green angiographies, infrared
      and blue reflectance (red-free) images, fundus autofluorescence images, and OCT
      scans (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). The
      combination of various macular diagnostic tools can lead to a better
      understanding and improved knowledge of macular diseases.

PMID- 22132314
TI  - Retinal degenerations: genetics, mechanisms, and therapies.

PMID- 22132311
TI  - Potential Therapeutic Roles for Inhibition of the PI3K/Akt/mTOR Pathway in the
      Pathophysiology of Diabetic Retinopathy.
AB  - Novel therapeutics such as inhibitors of PI3K/Akt/mTOR pathway presents a unique
      opportunity for the management of diabetic retinopathy (DR). Second generation
      mTOR inhibitors have the prospect to be efficacious in managing various stages of
      disease progression in DR. During early stages, the mTOR inhibitors suppress HIF
      1alpha, VEGF, leakage, and breakdown of the blood-retinal barrier. These mTOR
      inhibitors impart a pronounced inhibitory effect on inflammation, an early
      component with diverse ramifications influencing the progression of DR. These
      inhibitors suppress IKK and NF-kappaB along with downstream inflammatory
      cytokines, chemokines, and adhesion molecules. In proliferative DR, mTOR
      inhibitors suppress several growth factors that play pivotal roles in the
      induction of pathological angiogenesis. Lead mTOR inhibitors in clinical trials
      for ocular indications present an attractive treatment option for chronic use in
      DR with favorable safety profile and sustained ocular pharmacokinetics following
      single dose. Thereby, reducing dosing frequency and risk associated with chronic
      drug administration.

PMID- 22132315
TI  - Leukocyte adhesion molecules in diabetic retinopathy.
AB  - Diabetes is a systemic disease that causes a number of metabolic and physiologic
      abnormalities. One of the major microvascular complications of diabetes is
      diabetic retinopathy (DR), a leading cause of blindness in people over age 50.
      The mechanisms underlying the development of DR are not fully understood;
      however, extensive studies have recently implicated chronic, low-grade
      inflammation in the pathophysiology of DR. During inflammation leukocytes undergo
      sequential adhesive interactions with endothelial cells to migrate into the
      inflamed tissues, a process known as the "leukocyte recruitment cascade" which is
      orchestrated by precise adhesion molecule expression on the cell surface of
      leukocytes and the endothelium. This paper summarizes the recent clinical and
      preclinical works on the roles of leukocyte adhesion molecules in DR.

PMID- 22132317
TI  - Synthesis and application of functional nucleic acids.

PMID- 22132316
TI  - Anti-VEGF Agents for Ocular Angiogenesis and Vascular Permeability.
AB  - We review articles describing intravitreal injection of anti-VEGF drug trials,
      while discussing the mechanisms of the action of anti-VEGF antibodies, and also
      evaluating their outcomes. Intraocular injections of anti-VEGF drug are
      considered to be an effective treatment for macular edema after retinal vein
      occlusion, however, recurrent/persistent edema is common. The recent reports may
      lead to a shift in treatment paradigm for DME, from laser photocoagulation, to
      newer approaches using anti-VEGF drugs. There have been several well-publicized
      prospective, randomized studies that demonstrated the efficacy of intravitreal
      injection of anti-VEGF drugs for patients with AMD. Adjuvant bevacizumab for
      neovascular glaucoma may prevent further PAS formation, and it is likely to open
      up a therapeutic window for a panretinal photocoagulation and trabeculectomy.
      Intravitreal injection of bevacizumab (IVB) results in a substantial decrease in
      bleeding from the retinal vessels or new vessels during a standard vitrectomy.
      IVB has also been reported to be effective for inducing the regression of new
      vessels in proliferative diabetic retinopathy. The use of bevacizumab in stage 4
      or 5 retinopahty of permaturity (ROP) is to reduce the plus sign to help reduce
      hemorrhage during the subsequent vitrectomy. Some authors reported cases of
      resolution of stage 4 A ROP after bevacizumab injection.

PMID- 22132318
TI  - Splicing programs and cancer.
AB  - Numerous studies report splicing alterations in a multitude of cancers by using
      gene-by-gene analysis. However, understanding of the role of alternative splicing
      in cancer is now reaching a new level, thanks to the use of novel technologies
      allowing the analysis of splicing at a large-scale level. Genome-wide analyses of
      alternative splicing indicate that splicing alterations can affect the products
      of gene networks involved in key cellular programs. In addition, many splicing
      variants identified as being misregulated in cancer are expressed in normal
      tissues. These observations suggest that splicing programs contribute to specific
      cellular programs that are altered during cancer initiation and progression.
      Supporting this model, recent studies have identified splicing factors
      controlling cancer-associated splicing programs. The characterization of splicing
      programs and their regulation by splicing factors will allow a better
      understanding of the genetic mechanisms involved in cancer initiation and
      progression and the development of new therapeutic targets.

PMID- 22132319
TI  - Self-reported disability in adults with severe obesity.
AB  - Self-reported disability in performing daily life activities was assessed in
      adults with severe obesity (BMI >= 35 kg/m(2)) using the Health Assessment
      Questionnaire (HAQ). 262 participants were recruited into three BMI groups: Group
      I: 35-39.99 kg/m(2); Group II: 40-44.99 kg/m(2); Group III: >=45.0 kg/m(2).
      Progressively increasing HAQ scores were documented with higher BMI; Group I HAQ
      score: 0.125 (median) (range: 0-1.75); Group II HAQ score: 0.375 (0-2.5); Group
      III HAQ score: 0.75 (0-2.65) (Group III versus II P < 0.001; Group III versus I P
      < 0.001; Group II versus I P = 0.004). HAQ score strongly correlated with BMI and
      age. Nearly three-fourths of the study participants reported some degree of
      disability (HAQ score > 0). The prevalence of this degree of disability increased
      with increasing BMI and age. It also correlated to type 2 diabetes, metabolic
      syndrome, and clinical depression, but not to gender. Our data suggest that
      severe obesity is associated with self-reported disability in performing common
      daily life activities, with increasing degree of disability as BMI increases over
      35 kg/m(2). Functional assessment is crucial in obesity management, and
      establishing the disability profiles of obese patients is integral to both meet
      the specific healthcare needs of individuals and develop evidence-based public
      health programs, interventions, and priorities.

PMID- 22132320
TI  - Cardiomyocyte triglyceride accumulation and reduced ventricular function in mice
      with obesity reflect increased long chain Fatty Acid uptake and de novo Fatty
      Acid synthesis.
AB  - A nonarteriosclerotic cardiomyopathy is increasingly seen in obese patients.
      Seeking a rodent model, we studied cardiac histology, function, cardiomyocyte
      fatty acid uptake, and transporter gene expression in male C57BL/6J control mice
      and three obesity groups: similar mice fed a high-fat diet (HFD) and db/db and
      ob/ob mice. At sacrifice, all obesity groups had increased body and heart weights
      and fatty livers. By echocardiography, ejection fraction (EF) and fractional
      shortening (FS) of left ventricular diameter during systole were significantly
      reduced. The V(max) for saturable fatty acid uptake was increased and
      significantly correlated with cardiac triglycerides and insulin concentrations.
      V(max) also correlated with expression of genes for the cardiac fatty acid
      transporters Cd36 and Slc27a1. Genes for de novo fatty acid synthesis (Fasn,
      Scd1) were also upregulated. Ten oxidative phosphorylation pathway genes were
      downregulated, suggesting that a decrease in cardiomyocyte ATP synthesis might
      explain the decreased contractile function in obese hearts.

PMID- 22132321
TI  - Intervening to Reduce Sedentary Behaviors and Childhood Obesity among School-Age
      Youth: A Systematic Review of Randomized Trials.
AB  - Objective. To assess the effectiveness of interventions that focus on reducing
      sedentary behavior (SB) among school-age youth and to identify elements
      associated with interventions' potential for translation into practice settings.
      Methods. A comprehensive literature search was conducted using 4 databases for
      peer-reviewed studies published between 1980 and April 2011. Randomized trials,
      which lasted at least 12 weeks, aimed at decreasing SB among children aged 6 to
      19 years were identified. Results. Twelve studies were included; 3 focused only
      on SB, 1 focused on physical activity (PA), 6 were combined SB and PA
      interventions, and 2 studies targeted SB, PA, and diet. The majority of the
      studies were conducted in a school setting, while others were conducted in such
      settings as clinics, community centers, and libraries. Conclusions. Overall,
      interventions that focused on decreasing SB were associated with reduction in
      time spent on SB and/or improvements in anthropometric measurements related to
      childhood obesity. Several of the studies did consider elements related to the
      intervention's potential for translation into practice settings.

PMID- 22132322
TI  - Relationship between Processing Method and the Glycemic Indices of Ten Sweet
      Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica.
AB  - This study investigated the effect of different traditional cooking methods on
      glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas)
      cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting,
      baking, frying, or boiling then immediately consumed by the ten nondiabetic test
      subjects (5 males and 5 females; mean age of 27 +/- 2 years). The GI varied
      between 41 +/- 5-93 +/- 5 for the tubers studied. Samples prepared by boiling had
      the lowest GI (41 +/- 5-50 +/- 3), while those processed by baking (82 +/- 3-94
      +/- 3) and roasting (79 +/- 4-93 +/- 2) had the highest GI values. The study
      indicates that the glycemic index of Jamaican sweet potatoes varies significantly
      with the method of preparation and to a lesser extent on intravarietal
      differences. Consumption of boiled sweet potatoes could minimize postprandial
      blood glucose spikes and therefore, may prove to be more efficacious in the
      management of type 2 diabetes mellitus.

PMID- 22132324
TI  - Whole grains, legumes, and the subsequent meal effect: implications for blood
      glucose control and the role of fermentation.
AB  - Whole grains and legumes are known to reduce postprandial glycemia and, in some
      instances, insulinemia. However, the subsequent meal effect of ingesting whole
      grains and legumes is less well known. That is, inclusion of whole grains or
      legumes at breakfast decreases postprandial glycemia at lunch and/or dinner on
      the same day whereas consumption of a whole grain or lentil dinner reduces
      glycemia at breakfast the following morning. This effect is lost upon milling,
      processing, and cooking at high temperatures. The subsequent meal effect has
      important implications for the control of day-long blood glucose, and may be
      partly responsible for the reduction in diabetes incidence associated with
      increased whole grain and legume intake. This paper describes the subsequent meal
      effect and explores the role of acute glycemia, presence of resistant starch, and
      fermentation of indigestible carbohydrate as the mechanisms responsible for this
      effect.

PMID- 22132323
TI  - T2DM: Why Epigenetics?
AB  - Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder influenced by
      interactions between genetic and environmental factors. Epigenetics conveys
      specific environmental influences into phenotypic traits through a variety of
      mechanisms that are often installed in early life, then persist in differentiated
      tissues with the power to modulate the expression of many genes, although
      undergoing time-dependent alterations. There is still no evidence that
      epigenetics contributes significantly to the causes or transmission of T2DM from
      one generation to another, thus, to the current environment-driven epidemics, but
      it has become so likely, as pointed out in this paper, that one can expect an
      efflorescence of epigenetic knowledge about T2DM in times to come.

PMID- 22132325
TI  - Regulation of suppressors of cytokine signaling as a therapeutic approach in
      autoimmune diseases, with an emphasis on multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating, presumably autoimmune
      disease of the central nervous system (CNS). Among the available MS therapies,
      interferon (IFN)beta and the recently introduced statins have been reported to
      exert their immunomodulatory effects through the induction of SOCS1 and SOCS3 in
      various inflammatory cell subsets. The SOCS proteins negatively regulate cytokine
      and Toll-like receptors- (TLR-) induced signaling in the inflammatory cells.
      SOCS1 and SOCS3 have been reported to play an important role in the regulation of
      Th17-cell differentiation through their effects on the cells of the innate and
      adaptive immune systems. IFNbeta and statins inhibit Th17-cell differentiation
      directly and indirectly via induction of SOCS1 and SOCS3 expression in monocytes,
      dendritic cells (DCs), and B-cells. Due to their rapid induction and degradation,
      and SOCS-mediated regulation of multiple cytokine-signaling pathways, they
      represent an attractive therapeutic target in the autoimmune diseases, and
      particularly relapsing remitting (RR) MS.

PMID- 22132326
TI  - Molecular Characterization and SNP Detection of CD14 Gene of Crossbred Cattle.
AB  - CD14 is an important molecule for innate immunity that can act against a wide
      range of pathogens. The present paper has characterized CD14 gene of crossbred
      (CB) cattle (Bos indicus*Bos taurus). Cloning and sequence analysis of CD14 cDNA
      revealed 1119 nucleotide long open reading frame encoding 373 amino acids protein
      and 20 amino acids signal peptide. CB cattle CD14 gene exhibited a high
      percentage of nucleotide identity (59.3-98.1%) with the corresponding mammalian
      homologs. Cattle and buffalo appear to have diverged from a common ancestor in
      phylogenetic analysis. 25 SNPs with 17 amino acid changes were newly reported and
      the site for mutational hot-spot was detected in CB cattle CD14 gene. Non
      synonymous substitutions exceeding synonymous substitutions indicate the
      evolution of this protein through positive selection among domestic animals.
      Predicted protein structures obtained from deduced amino acid sequence indicated
      CB cattle CD14 molecule to be a receptor with horse shoe-shaped structure. The
      sites for LPS binding, LPS signalling, leucine-rich repeats, putative N-linked
      glycosylation, O-linked glycosylation, glycosyl phosphatidyl inositol anchor,
      disulphide bridges, alpha helix, beta strand, leucine rich nuclear export signal,
      leucine zipper and domain linker were predicted. Most of leucine and cysteine
      residues remain conserved across the species.

PMID- 22132327
TI  - A population where men live as long as women: villagrande strisaili, sardinia.
AB  - Usually women live longer than men and female centenarians largely outnumber male
      centenarians. The findings of previous studies identifying a population with a
      femininity ratio close to 1.0 among centenarians in the mountainous region of
      Sardinia was the starting point of an in-depth investigation in order to compare
      mortality trajectories between men and women in that population. The exceptional
      survival of men compared to women emerges from the comparison with similar
      Italian data. Age exaggeration for men has been strictly excluded as a result of
      the age validation procedure. The discussion suggests that besides
      biological/genetic factors, the behavioral factors including life style,
      demographic behavior, family support, and community characteristics may play an
      important role. No single explanation is likely to account for such an
      exceptional situation and a fully integrated multidisciplinary approach is
      urgently needed.

PMID- 22132328
TI  - Practice-oriented retest learning as the basic form of cognitive plasticity of
      the aging brain.
AB  - It has been well documented that aging is associated with declines in a variety
      of cognitive functions. A growing body of research shows that the age-related
      cognitive declines are reversible through cognitive training programs, suggesting
      maintained cognitive plasticity of the aging brain. Retest learning represents a
      basic form of cognitive plasticity. It has been consistently demonstrated for
      adults in young-old and old-old ages. Accumulated research indicates that retest
      learning is effective, robust, endurable and could occur at a more conceptual
      level beyond item-specific memorization. Recent studies also demonstrate
      promisingly broader transfer effects from retest practice of activities involving
      complex executive functioning to other untrained tasks. The results shed light on
      the development of self-guided mental exercise programs to improve cognitive
      performance and efficiency of the aging brain. The relevant studies were
      reviewed, and the findings were discussed in light of their limitations,
      implications, and future directions.

PMID- 22132329
TI  - Diffusion Tensor Imaging Evaluation of Corticospinal Tract Hyperintensity in
      Upper Motor Neuron-Predominant ALS Patients.
AB  - Amyotrophic lateral sclerosis (ALS) patients with predominant upper motor neuron
      (UMN) signs occasionally have hyperintensity of corticospinal tract (CST) on T2-
      and proton-density-(PD-) weighted brain images. Diffusion tensor imaging (DTI)
      was used to assess whether diffusion parameters along intracranial CST differ in
      presence or absence of hyperintensity and correspond to UMN dysfunction. DTI
      brain scans were acquired in 47 UMN-predominant ALS patients with (n = 21) or
      without (n = 26) CST hyperintensity and in 10 control subjects. Fractional
      anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial
      diffusivity (RD) were measured in four regions of interests (ROIs) along CST.
      Abnormalities (P < 0.05) were observed in FA, AD, or RD in CST primarily at
      internal capsule (IC) level in ALS patients, especially those with CST
      hyperintensity. Clinical measures corresponded well with DTI changes at IC level.
      The IC abnormalities suggest a prominent axonopathy in UMN-predominant ALS and
      that tissue changes underlying CST hyperintensity have specific DTI changes,
      suggestive of unique axonal pathology.

PMID- 22132331
TI  - Lessons from a mouse model characterizing features of vascular cognitive
      impairment with white matter changes.
AB  - With the demographic shift in age in advanced countries inexorably set to
      progress in the 21st century, dementia will become one of the most important
      health problems worldwide. Vascular cognitive impairment is the second most
      common type of dementia after Alzheimer's disease and is frequently responsible
      for the cognitive decline of the elderly. It is characterized by cerebrovascular
      white matter changes; thus, in order to investigate the underlying mechanisms
      involved in white matter changes, a mouse model of chronic cerebral hypoperfusion
      has been developed, which involves the narrowing of the bilateral common carotid
      arteries with newly designed microcoils. The purpose of this paper is to provide
      a comprehensive summary of the achievements made with the model that shows good
      reproducibility of the white matter changes characterized by blood-brain barrier
      disruption, glial activation, oxidative stress, and oligodendrocyte loss
      following chronic cerebral hypoperfusion. Detailed characterization of this model
      may help to decipher the substrates associated with impaired memory and move
      toward a more integrated therapy of vascular cognitive impairment.

PMID- 22132330
TI  - Neuroinflammation and cerebrovascular disease in old age: a translational
      medicine perspective.
AB  - The incidence of cerebrovascular disease is highest in the elderly population.
      However, the pathophysiological mechanisms of brain response to cerebral ischemia
      in old age are currently poorly understood. Ischemic changes in the commonly used
      young animal stroke models do not reflect the molecular changes associated with
      the aged brain. Neuroinflammation and oxidative stress are important pathogenic
      processes occurring during the acute phase of cerebral ischemia. Free radical
      generation is also implicated in the aging process, and the combination of these
      effects in elderly stroke patients could explain the higher risk of morbidity and
      mortality. A better understanding of stroke pathophysiology in the elderly
      patient would assist in the development of new therapeutic strategies for this
      vulnerable age group. With the increasing use of reperfusion therapies,
      inflammatory pathways and oxidative stress remain attractive therapeutic targets
      for the development of adjuvant neuroprotective agents. This paper will discuss
      these molecular aspects of acute stroke and senescence from a bench-to-bedside
      research perspective.

PMID- 22132332
TI  - Dementia home care resources: how are we managing?
AB  - With the number of people living with dementia expected to more than double
      within the next 25 years, the demand for dementia home care services will
      increase. In this critical ethnographic study, we drew upon interview and
      participant data with persons with dementia, family caregivers, in-home
      providers, and case managers in nine dementia care networks to examine the
      management of dementia home care resources. Three interrelated, dialectical
      themes were identified: (1) finite formal care-inexhaustible familial care, (2)
      accessible resources rhetoric-Iinaccessible resources reality, and (3)
      diminishing care resources-increasing care needs. The development of policies and
      practices that provide available, accessible, and appropriate resources, ensuring
      equitable, not necessarily equal, distribution of dementia care resources is
      required if we are to meet the goal of aging in place now and in the future.

PMID- 22132333
TI  - Epitope analysis of cerebrospinal fluid IgG in Japanese multiple sclerosis
      patients using phage display method.
AB  - To investigate the antigen recognized by cerebrospinal fluid (CSF) high affinity
      IgG in patients with multiple sclerosis (MS), the phage display method was
      applied to the CSF from 15 MS and 10 control patients. Peptide sequences
      recognized by MS and control CSF IgG were individual specific, and no common
      motif was found. Peptide sequences frequently showed homology to various kinds of
      amino acid sequences of ubiquitous viruses such as epstein barr virus (EBV) and
      herpes simplex virus (HSV), although the frequency was not specific to MS
      patients. MS CSF IgG may recognize various types of ubiquitous viral antigen and
      may be increased by a bystander response.

PMID- 22132334
TI  - Relationship between periodontal diseases and preterm birth: recent
      epidemiological and biological data.
AB  - For ten years, the incidence of preterm birth does not decrease in developed
      countries despite the promotion of public health programs. Many risk factors have
      been identified including ethnicity, age, tobacco, and infection. However, almost
      50% of preterm birth causes remain unknown. The periodontal diseases are highly
      prevalent inflammatory and infectious diseases of tooth supporting tissues
      leading to an oral disability. They influence negatively general health worsening
      cardiovascular diseases and diabetes. Periodontal diseases have been also
      suspected to increase the rate of preterm birth, but data remain contradictory.
      The objective of this review is to present the principal results of
      epidemiological, biological, and interventional studies on the link between
      periodontal diseases and preterm birth. The conclusions of this work underline
      the importance for the physician/obstetrician to identify women at risk for
      preterm birth and to address these patients to dentist for periodontal
      examination and treatment in order to limit adverse pregnancy outcomes.

PMID- 22132335
TI  - An obesity-related FTO variant and the risk of preeclampsia in a Finnish study
      population.
AB  - Previous studies have demonstrated a common variant of the obesity and fat mass
      related FTO gene, rs9939609, to be associated with obesity, type 2 diabetes, and
      elevated blood pressure. We investigated whether the FTO SNP rs9939609 is
      associated with the risk of preeclampsia (PE) in a Finnish study population. 485
      women with prior PE and 449 women who had given birth after a normotensive
      pregnancy were genotyped (TaqMan) for the SNP rs9939609. The prevalences of
      genotypes AA, AT, and TT were 15%, 53%, and 32%, respectively, among the PE
      cases, and 16%, 47%, and 37%, respectively, among the controls (P = 0.199). We
      found no evidence of an association between the FTO SNP rs9939609 and PE.
      However, our cases were dominated by severe, early-onset PE. Thus, we are unable
      to exclude an association with the milder, later-onset form of the disease in
      which the role of maternal metabolic predisposition could be more significant.

PMID- 22132336
TI  - Prelabour caesarean section following IVF/ICSI in older-term nulliparous women:
      too precious to push?
AB  - OBJECTIVE: To compare prelabour caesarean section (CS) rates in older nulliparous
      women with a term singleton baby in cephalic presentation conceiving
      spontaneously and through IVF/ICSI. When the latter women would ask for CS, how
      willing are gynaecologists to comply with that request? METHODS: A population
      based retrospective (1995-2009) cohort study, conducted in Northern Belgium. A
      comparison of 1,866 nulliparous women pregnant after IVF/ICSI and 15,228 controls
      is made. An anonymous postal questionnaire is sent to all Belgian gynaecologists.
      RESULT: Both groups are comparable with respect to maternal age, gestational age,
      and birth weight. Prelabour CS is more often performed in women who conceived
      through IVF/ICSI compared to those who conceived spontaneously (9.2% versus 6.3%,
      P < 0.001). One in five gynaecologists agrees with the maternal request.
      CONCLUSION: IVF/ICSI pregnancies in older nulliparous women more often end in a
      prelabour CS and a substantial number of gynaecologists go along with a
      nonmedical reason for CS.

PMID- 22132337
TI  - Comparison of naturally conceived and IVF-DZ twins in the Netherlands Twin
      Registry: a developmental study.
AB  - In a large set of twin pairs, we compared twins born after IVF to naturally
      conceived twins with respect to birth characteristics, growth, attainment of
      motor milestones, and emotional and behavioral problems. Twin families were
      registered with the Netherlands Twin Register. We included 1534 dizygotic (DZ)
      twins born after IVF, 5315 naturally conceived (NC) DZ twins, and 1504 control NC
      DZ twins who were matched to the IVF twins based on maternal age, maternal
      educational level, smoking during pregnancy, gestational age, and offspring sex.
      Data were obtained by longitudinal surveys sent to fathers, mothers, and teachers
      at ages 1, 2, 3, 7, 10, and 12 years. Results showed no differences in growth, in
      attainment of motor milestones, and in behavioral development between IVF and
      matched NC twins. It can be concluded that for nearly all aspects, development in
      IVF and NC children is similar.

PMID- 22132338
TI  - Effect of angiotensin II on the left ventricular function in a near-term fetal
      sheep with metabolic acidemia.
AB  - We tested the hypothesis that, in acute metabolic acidemia, the fetal left
      ventricle (LV) has the capacity to increase its contractility in response to
      angiotensin II infusion. Eleven ewes and their fetuses were instrumented at 127
      138/145 days of gestation. The effect of angiotensin II on fetal LV function was
      assessed using intraventricular pressure catheter and tissue Doppler imaging
      (TDI). Angiotensin II increased fetal arterial blood pressure, whereas pH and
      pO(2) decreased. The heart rate and systemic venous pressure were not affected
      significantly. The LV end-diastolic and end-systolic pressures, as well as
      dP/dt(max), increased. The TDI-derived LV longitudinal myocardial isovolumic
      contraction velocity and its acceleration and velocity during early filling were
      higher than those at baseline. The incidence of absent isovolumic relaxation
      velocity was greater during angiotensin II infusion. In summary, during acute
      metabolic acidemia, the fetal left ventricle could increase its contractility in
      response to inotropic stimulus even in the presence of increased afterload. The
      diastolic LV function parameters were altered by angiotensin II.

PMID- 22132339
TI  - Tuberculosis in pregnancy: a review.
AB  - Tuberculosis (TB) was declared a public health emergency by WHO in 2005. The
      disease is a significant contributor to maternal mortality and is among the three
      leading causes of death among women aged 15-45 years in high burden areas. The
      exact incidence of tuberculosis in pregnancy, though not readily available, is
      expected to be as high as in the general population. Diagnosis of tuberculosis in
      pregnancy may be challenging, as the symptoms may initially be ascribed to the
      pregnancy, and the normal weight gain in pregnancy may temporarily mask the
      associated weight loss. Obstetric complications of TB include spontaneous
      abortion, small for date uterus, preterm labour, low birth weight, and increased
      neonatal mortality. Congenital TB though rare, is associated with high perinatal
      mortality. Rifampicin, INH and Ethambutol are the first line drugs while
      Pyrazinamide use in pregnancy is gaining popularity. Isoniazid preventive therapy
      is a WHO innovation aimed at reducing the infection in HIV positive pregnant
      women. Babies born to this mother should be commenced on INH prophylaxis for six
      months, after which they are vaccinated with BCG if they test negative.
      Successful control of TB demands improved living conditions, public
      enlightenment, primary prevention of HIV/AIDS and BCG vaccination.

PMID- 22132340
TI  - Ulcerative granular cell tumor: a clinicopathological and immunohistochemical
      study.
AB  - Granular cell tumor (GCT) is uncommonly presented with cutaneous ulcer. We
      examined the clinicopathological and immunohistochemical features of this
      ulcerative form in fourteen cases that may raise the awareness of this variant.
      The study included 11 males and 3 females with a mean age 31.5 +/- 7.42 years.
      All cases were presented with large solitary ulcer with indurated base, elevated
      border, skin colored margin, and necrotic floor. Twelve lesions were located on
      the extremities and two lesions on the genital region. Histologically, the
      lesions showed dermal infiltrate composed of large polygonal cells with granular
      cytoplasm and characteristic infiltration of the dermal muscles in all cases.
      Immunostaining showed positive reaction for S100 (14/14), NSE (14/14), CD68
      (5/14), and Vimentin (7/14) while HMB45, CK, EMA, and Desmin were negative. We
      hope that this paper increases the awareness of ulcerative GCT and consider it in
      the differential diagnosis of ulcerative lesions.

PMID- 22132341
TI  - Nanotechnology in advanced drug delivery.

PMID- 22132344
TI  - Age-related changes in bone remodelling and structure in men: histomorphometric
      studies.
AB  - Histomorphometric studies of the age-related changes in bone remodelling and
      structure in men are relatively sparse and mainly limited to the iliac crest. The
      available data indicate that loss of trabecular bone is predominantly due to
      decreased formation at the level of individual bone remodelling units and that an
      increase in remodelling rate does not play a major role. The main structural
      consequence of the changes in bone remodelling is trabecular thinning. In
      cortical bone, an age-related reduction in cortical width and increase in
      porosity have been demonstrated at several skeletal sites. However, the
      alterations in bone remodelling responsible for these changes remain to be
      established.

PMID- 22132343
TI  - Molecular Mechanisms Underlying the Link between Nuclear Receptor Function and
      Cholesterol Gallstone Formation.
AB  - Cholesterol gallstone disease is highly prevalent in western countries,
      particularly in women and some specific ethnic groups. The formation of water
      insoluble cholesterol crystals is due to a misbalance between the three major
      lipids present in the bile: cholesterol, bile salts, and phospholipids. Many
      proteins implicated in biliary lipid secretion in the liver are regulated by
      several transcription factors, including nuclear receptors LXR and FXR. Human and
      murine genetic, physiological, pathophysiological, and pharmacological evidence
      is consistent with the relevance of these nuclear receptors in gallstone
      formation. In addition, there is emerging data that also suggests a role for
      estrogen receptor ESR1 in abnormal cholesterol metabolism leading to gallstone
      disease. A better comprehension of the role of nuclear receptor function in
      gallstone formation may help to design new and more effective therapeutic
      strategies for this highly prevalent disease condition.

PMID- 22132342
TI  - Ezetimibe: its novel effects on the prevention and the treatment of cholesterol
      gallstones and nonalcoholic Fatty liver disease.
AB  - The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma
      cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein
      (NPC1L1), an intestinal sterol influx transporter that can actively facilitate
      the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe
      treatment also induces a complete resistance to cholesterol gallstone formation
      and nonalcoholic fatty liver disease (NAFLD) in addition to preventing
      hypercholesterolemia in mice on a Western diet. Because chylomicrons are the
      vehicles with which the enterocytes transport cholesterol and fatty acids into
      the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases
      possibly through the regulation of chylomicron-derived cholesterol and fatty acid
      metabolism in the liver. It is highly likely that there is an intestinal and
      hepatic cross-talk through the chylomicron pathway. Therefore, understanding the
      molecular mechanisms whereby cholesterol and fatty acids are absorbed from the
      intestine could offer an efficacious novel approach to the prevention and the
      treatment of cholesterol gallstones and NAFLD.

PMID- 22132345
TI  - Therapy of osteoporosis in men with teriparatide.
AB  - Osteoanabolic therapy is an attractive therapeutic option for men with
      osteoporosis because it directly stimulates bone formation, an action not shared
      by any antiresorptive drug. Teriparatide (recombinant human PTH(1-34)) and PTH(1
      84) are available in many countries but PTH(1-84) is not available in the United
      States. Only teriparatide is approved for the treatment of osteoporosis in men.
      It is also indicated in glucocorticoid-induced osteoporosis. Teriparatide is
      associated with major gains in bone density at the lumbar spine and, to a lesser
      extent, in the hip regions. Vertebral and nonvertebral fractures are reduced in
      postmenopausal women treated with teriparatide. Fracture reduction data in men
      are less secure because the number of study subjects is small and the studies
      have not been powered to document this endpoint. Nevertheless, observational data
      in men suggest a reduction in vertebral fractures with teriparatide. Attempts to
      show further beneficial effects of teriparatide in combination with
      antiresorptive agents have not been demonstrated yet to be superior to
      monotherapy with teriparatide alone. The duration of therapy with teriparatide is
      limited to 2 years. Thereafter, it is necessary to treat with an antiresorptive
      drug to maintain, and perhaps increase, densitometric gains. Teriparatide is well
      tolerated with a good safety profile.

PMID- 22132346
TI  - Maternal Thyroid Function during the Second Half of Pregnancy and Child
      Neurodevelopment at 6, 12, 24, and 60 Months of Age.
AB  - Although evidence suggests that maternal hypothyroidism and mild hypothyroxinemia
      during the first half of pregnancy alters fetal neurodevelopment among euthyroid
      offspring, little data are available from later in gestation. In this study, we
      measured free T4 using direct equilibrium dialysis, as well as total T4 and TSH
      in 287 pregnant women at 27 weeks' gestation. We also assessed cognition, memory,
      language, motor functioning, and behavior in their children at 6, 12, 24, and 60
      months of age. Increasing maternal TSH was related to better performance on tests
      of cognition and language at 12 months but not at later ages. At 60 months, there
      was inconsistent evidence that higher TSH was related to improved attention. We
      found no convincing evidence that maternal TH during the second half of pregnancy
      was related to impaired child neurodevelopment.

PMID- 22132348
TI  - Transient ischemic attack associated with trazodone therapy: a case report.

PMID- 22132347
TI  - Atypical clinical manifestations of graves' disease: an analysis in depth.
AB  - Over the past few decades, there has been an increase in the number of reports
      about newly recognized (atypical or unusual) manifestations of Graves' disease
      (GD), that are related to various body systems. One of these manifestations is
      sometimes the main presenting feature of GD. Some of the atypical manifestations
      are specifically related to GD, while others are also similarly seen in patients
      with other forms of hyperthyroidism. Lack of knowledge of the association between
      these findings and GD may lead to delay in diagnosis, misdiagnosis, or
      unnecessary investigations. The atypical clinical presentations of GD include
      anemia, vomiting, jaundice, and right heart failure. There is one type of anemia
      that is not explained by any of the known etiological factors and responds well
      to hyperthyroidism treatment. This type of anemia resembles anemia of chronic
      disease and may be termed GD anemia. Other forms of anemia that are associated
      with GD include pernicious anemia, iron deficiency anemia of celiac disease, and
      autoimmune hemolytic anemia. Vomiting has been reported as a presenting feature
      of Graves' disease. Some cases had the typical findings of hyperthyroidism
      initially masked, and the vomiting did not improve until hyperthyroidism has been
      detected and treated. Hyperthyroidism may present with jaundice, and on the other
      hand, deep jaundice may develop with the onset of overt hyperthyroidism in
      previously compensated chronic liver disease patients. Pulmonary hypertension is
      reported to be associated with GD and to respond to its treatment. GD-related
      pulmonary hypertension may be so severe to produce isolated right-sided heart
      failure that is occasionally found as the presenting manifestation of GD.

PMID- 22132349
TI  - Medically self-sabotaging behavior and multiple symptoms on the review of
      systems.

PMID- 22132350
TI  - Satisfaction with medication is correlated with outcome but not persistence in
      patients treated with placebo, escitalopram, or serotonin-norepinephrine reuptake
      inhibitors: a post hoc analysis.
AB  - OBJECTIVE: To test whether satisfaction with taking medication, assessed using
      item 15 of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES
      Q), is associated with clinical outcome and persistence with treatment. METHOD:
      In this post hoc analysis, data were analyzed from 4 randomized placebo
      controlled studies of patients with major depressive disorder treated with
      escitalopram (650 patients taking escitalopram and 534 taking placebo), together
      with data from 2 randomized trials of escitalopram versus venlafaxine or
      duloxetine (235 patients taking escitalopram and 233 taking a serotonin
      norepinephrine reuptake inhibitor). The studies were published between 2002 and
      2007. Instruments included the Q-LES-Q, which was assessed at baseline and week
      8, and the Montgomery-Asberg Depression Rating Scale (MADRS), which was assessed
      at baseline and weeks 1, 2, 4, 6, and 8. RESULTS: At baseline, the mean +/- SD
      MADRS total score was 30.0 +/- 4.6, and the mean Q-LES-Q item 15 score was 2.9 +/
      0.9. At week 8, the MADRS response rates of placebo-treated patients with a low,
      moderate, or high satisfaction with medication at baseline were 30%, 37%, and
      46%, respectively (mixed model repeated measures [MMRM]). The corresponding MADRS
      response rates for escitalopram-treated patients with a low, moderate, or high
      satisfaction at baseline were 56%, 60%, and 67%, respectively (MMRM). Baseline
      satisfaction with medication was not significantly correlated with time to
      withdrawal (all reasons). The change in satisfaction with medication from
      baseline to endpoint was significantly correlated with symptomatic improvement on
      the MADRS (P < .001). CONCLUSIONS: Baseline satisfaction with medication after 1
      week of placebo run-in is a moderator of treatment outcome but not of persistence
      of treatment in the acute treatment phase of depressed outpatients. Patient
      attitude toward medication should be taken into account before treatment is
      initiated.

PMID- 22132351
TI  - Clinical effectiveness of using an integrated model to treat depressive symptoms
      in veterans affairs primary care clinics and its impact on health care
      utilization.
AB  - OBJECTIVE: To determine if veterans treated in an integrated mental health
      program within a Veterans Affairs (VA) primary care clinic sustained long-term
      improvement in depressive symptoms and changed their use of health care. METHOD:
      In this pilot program, 72 veterans were offered short-term treatment for
      depressive symptoms by a colocated psychiatrist who was integrated into a VA
      primary care team (October 1, 1997, through September 30, 1999). Patients were
      assessed initially and at their final session using the Hamilton Depression
      Rating Scale. Veterans who completed treatment were referred back to their
      primary care provider or to specialty mental health services. Patients were
      contacted and invited to be reevaluated 3 to 5 years later using the same measure
      (December 1, 2001, through November 30, 2002). Health care utilization data were
      collected for 1 year preintervention and 2 years postintervention. Outcomes for
      treatment completers were compared to outcomes for those who declined or dropped
      out of treatment. RESULTS: Of 48 patients who agreed to participate in the study,
      27 completed treatment and showed a significant decline in symptoms from
      pretreatment to follow-up (P = .008) compared to 16 noncompleters, as well as a
      moderate-to-large between-group effect size (d = 0.78) and trends for higher
      remission and response rates. Completers ranked significantly higher in the
      number of antidepressant prescriptions filled before (P = .002) and after
      treatment (P = .001) and in the number of medical visits postintervention (year
      1: P = .021; year 2: P = .023), without an associated cost increase. CONCLUSIONS:
      Colocated mental health care integrated into VA primary care is associated with
      sustained improvement of depressive symptoms in a heterogeneous patient
      population with a high incidence of psychiatric comorbidities. This finding
      compares favorably with the results of earlier controlled clinical trials and
      suggests a potential effect on health care utilization.

PMID- 22132352
TI  - Psychoeducation for patients with a psychotic disorder: effects on knowledge and
      coping.
AB  - OBJECTIVE: Psychoeducation is an essential and promising element in the
      nonpharmacologic treatment of patients with a psychotic disorder. This study
      examined the effects of patient-directed psychoeducation on knowledge and coping.
      METHOD: This study included 99 primary care patients with a psychotic disorder
      according to DSM-IV-TR criteria who completed a knowledge questionnaire before
      and a knowledge and coping questionnaire halfway through, immediately after, and
      6 months after a 20-session group psychoeducation program. The first time the
      program was given was between April and October 2007, and the final time the
      program was given was between October 2009 and April 2010. Results were analyzed
      with multilevel analysis. RESULTS: Knowledge increased significantly from the
      beginning of the program to halfway through the program (P < .001), even after
      correction for baseline scores, but not any further thereafter. Coping improved
      from halfway through the program to the end of the program (P = .02), also after
      correction for baseline scores, but not thereafter. Only at 6 months after the
      program was knowledge related to coping (P = .01). There were no differences in
      knowledge and coping between male and female patients. Halfway through (P = .001)
      and at the end of the program (P = .02), the increase in knowledge was
      significantly lower for patients taking atypical antipsychotic medication than
      for patients taking typical antipsychotic medication. CONCLUSIONS: In patients
      with a psychotic disorder, psychoeducation results in more knowledge immediately
      and several months after the program and contributes to better coping only
      immediately after the program. Patients with more knowledge several months after
      psychoeducation may also be patients who then cope better with the disorder.

PMID- 22132353
TI  - Effectiveness of yoga therapy as a complementary treatment for major psychiatric
      disorders: a meta-analysis.
AB  - OBJECTIVE: To examine the efficacy of yoga therapy as a complementary treatment
      for psychiatric disorders such as schizophrenia, depression, anxiety, and
      posttraumatic stress disorder (PTSD). DATA SOURCES: Eligible trials were
      identified by a literature search of PubMed/MEDLINE, Cochrane Control Trials
      Register, Google Scholar, and EBSCO on the basis of criteria of acceptable
      quality and relevance. The search was performed using the following terms: yoga
      for schizophrenia, yoga for depression, yoga for anxiety, yoga for PTSD, yoga
      therapy, yoga for psychiatric disorders, complementary treatment, and efficacy of
      yoga therapy. Trials both unpublished and published with no limitation placed on
      year of publication were included; however, the oldest article included in the
      final meta-analysis was published in 2000. STUDY SELECTION: All available
      randomized, controlled trials of yoga for the treatment of mental illness were
      reviewed, and 10 studies were eligible for inclusion. As very few randomized,
      controlled studies have examined yoga for mental illness, this meta-analysis
      includes studies with participants who were diagnosed with mental illness, as
      well as studies with participants who were not diagnosed with mental illness but
      reported symptoms of mental illness. Trials were excluded due to the following:
      (1) insufficient information, (2) inadequate statistical analysis, (3) yoga was
      not the central component of the intervention, (4) subjects were not diagnosed
      with or did not report experiencing symptoms of one of the psychiatric disorders
      of interest (ie, schizophrenia, depression, anxiety, and PTSD), (5) study was not
      reported in English, and (6) study did not include a control group. DATA
      EXTRACTION: Data were extracted on participant diagnosis, inclusion criteria,
      treatment and control groups, duration of intervention, and results (pre-post
      mean and standard deviations, t values, and f values). Number, age, and sex ratio
      of participants were also obtained when available. DATA SYNTHESIS: The combined
      analysis of all 10 studies provided a pooled effect size of -3.25 (95% CI, -5.36
      to -1.14; P = .002), indicating that yoga-based interventions have a
      statistically significant effect as an adjunct treatment for major psychiatric
      disorders. Findings in support of alternative and complementary interventions may
      especially be an aid in the treatment of disorders for which current treatments
      are found to be inadequate or to carry severe liabilities. CONCLUSIONS: As
      current psychopharmacologic interventions for severe mental illness are
      associated with increased risk of weight gain as well as other metabolic side
      effects that increase patients' risk for cardiovascular disease, yoga may be an
      effective, far less toxic adjunct treatment option for severe mental illness.

PMID- 22132354
TI  - The clinical management of bipolar disorder: a review of evidence-based
      guidelines.
AB  - OBJECTIVE: To discuss the criteria used to diagnose the mood episodes that
      constitute bipolar disorder, the approach to the differential diagnosis of these
      presentations, and the evidence-based treatments that are currently available.
      DATA SOURCES: A search for evidence-based guidelines for the diagnosis and
      treatment of adults with bipolar disorder was performed on May 5, 2010, using the
      National Guideline Clearinghouse database, the Agency for Healthcare Research and
      Quality Evidence Reports database, and the Cochrane Database of Systematic
      Reviews. In addition, a clinical query of the PubMed database (completed March 1,
      2010) and searches of drug manufacturers' Web sites (for unpublished trials) were
      performed to identify randomized, controlled trials and meta-analyses evaluating
      strategies to treat resistant depression. STUDY SELECTION: Guidelines were
      selected based on data from randomized, controlled trials; meta-analyses; and
      well-conducted naturalistic trials that were published since 2005. DATA
      EXTRACTION: Four evidence-based treatment guidelines for bipolar disorder were
      included. Three were published in 2009: those put forth as part of an Australian
      project, those of the British Association for Psychopharmacology, and those
      produced by the International Society for Bipolar Disorders and the Canadian
      Network for Mood and Anxiety Treatments. The most recent US guidelines are that
      of the Texas Implementation of Medication Algorithms project, last updated in
      2005. DATA SYNTHESIS: Recommendations from all 4 guidelines were reviewed and are
      presented with a focus on using them to improve clinical care. The
      recommendations with the most agreement and highest level of clinical evidence
      were as follows: (1) mania should be treated first-line with lithium, divalproex,
      or an atypical antipsychotic medication; (2) mixed episodes should be treated
      first-line with divalproex or an atypical antipsychotic; (3) bipolar depression
      should be treated with quetiapine, olanzapine/fluoxetine combination, or
      lamotrigine; and (4) all patients should be offered group or individual
      psychoeducation. Additionally, recommendations for therapeutic drug monitoring
      are presented due to their importance for patient safety, particularly for the
      primary care physician, although these are based on consensus guidelines.
      CONCLUSIONS: Bipolar disorder is a lifelong illness that is complicated by high
      comorbidity and risk of poor health outcomes, making the primary care physician's
      role vital in improving patient quality of life. The management of acute mood
      episodes should focus first on safety, should include psychiatric consultation as
      soon as possible, and should begin with an evidence-based treatment that may be
      continued into the maintenance phase. Long-term management focuses on maintenance
      of euthymia, requires ongoing medication, and may benefit from adjunctive
      psychotherapy.

PMID- 22132355
TI  - Mild cognitive impairment: diagnosis and treatment dilemmas.

PMID- 22132356
TI  - Fainting, swooning, and syncope.

PMID- 22132357
TI  - Befriending.

PMID- 22132358
TI  - Diabetes insipidus secondary to combination atypical antipsychotic and lithium
      use in a bipolar disorder patient: a case report.

PMID- 22132359
TI  - The horse with stripes: a case of anti-NMDA receptor encephalitis.

PMID- 22132360
TI  - Hair loss associated with escitalopram but not with venlafaxine: a case report.

PMID- 22132361
TI  - Sertraline and low-dose doxepin treatment in severe agitated-anxious depression
      with significant gastrointestinal complaints:two case reports.

PMID- 22132362
TI  - Prolactin-a biomarker for antipsychotic treatment response?

PMID- 22132363
TI  - Open trial of brief behavioral activation psychotherapy for depression in an
      integrated veterans affairs primary care setting.
AB  - OBJECTIVE: Major depressive disorder (MDD) is highly prevalent and impairing and
      highly likely to present in primary care settings. Recent efforts by the
      Department of Veterans Affairs (VA) have sought to integrate mental health
      services into primary care settings, leading to new specialty pharmacotherapy and
      psychotherapy treatment options for primary care patients. However, little is
      known about the effectiveness of these new services in primary care patients with
      MDD. The present study investigated the effectiveness of a brief, easy-to
      administer, evidence-based psychotherapy behavioral activation in an integrated
      mental health/primary care setting in a southeastern VA medical center during the
      first year of the program. METHOD: Thirty-five veterans with MDD (DSM-IV
      criteria) completed an initial clinical intake, were given the Mini International
      Neuropsychiatric Interview, and began a 4-week behavioral activation program.
      Patients also completed the Hospital Anxiety and Depression Scale (HADS) at
      intake, posttreatment, and at 1-month follow-up. The study was conducted from
      November 2009 to November 2010. RESULTS: Sixty percent (n = 21) of patients
      completed the brief behavioral activation. Treatment completers demonstrated
      significant reductions in symptoms of both anxiety and depression on the HADS at
      posttreatment (t values > 5.2, P values < .001, d values > 1.16, g values > 1.02)
      and follow-up (t values > 4.0, P values < .01, d values > 1.74, g values > 1.67)
      when compared to pretreatment levels. CONCLUSIONS: The present findings support
      the use of behavioral activation as an effective treatment for patients with MDD
      in a primary care setting. These findings suggest that new integrated primary
      care settings should incorporate behavioral activation to offer brief, evidence
      based treatments that provide reliable symptom reductions in addition to possible
      reductions in treatment needs and better management of related physical health
      conditions.

PMID- 22132364
TI  - Aggressive patient behaviors related to medical care: a cross-sectional self
      report survey.
AB  - OBJECTIVE: To examine the self-reported prevalence of aggressive and/or
      disruptive behaviors by patients as related to their medical care. METHOD: In a
      cross-sectional, consecutive sample of internal medicine outpatients (N = 397),
      respondents reported on 17 aggressive and/or disruptive behaviors related to
      their medical care. Data were collected during November 2010. RESULTS: In this
      sample, 48.9% of respondents endorsed at least 1 of the proposed aggressive
      behaviors; 9.1% endorsed 1 behavior, 20.4% endorsed 2 behaviors, 10.3% endorsed 3
      behaviors, 5.5% endorsed 4 behaviors, and 3.5% endorsed 5 or more behaviors (the
      maximum being 11). The most commonly reported behaviors were talking negatively
      about medical personnel to family (41.3%) and friends (39.5%), threatening to hit
      or strike medical personnel (7.1%), and refusing to pay a bill because of
      dissatisfaction or anger (6.8%). No participant reported being escorted off
      premises by security or being charged with assault in a medical setting. For
      those who reported 1 or more aggressive behaviors, there were no gender
      differences, but younger and better educated patients were more likely to report
      such behaviors. CONCLUSIONS: While the majority of patients do not evidence
      aggressive behaviors related to their medical care, a small minority do report
      such behavior, some of which can be disruptive as well as dangerous.

PMID- 22132365
TI  - Managing bipolar disorder in the primary care setting: a perspective for mental
      health professionals.
AB  - Bipolar disorder affects between 1.3 percent and 1.6 percent of the general
      population. According to available evidence, prevalence rates appear to be even
      higher in primary care settings. The diagnosis and management of patients with
      bipolar disorder are potentially complicated by a number of factors, including
      underdiagnosis due to the predominance of depressive symptoms; high levels of
      psychiatric comorbidity; a comparatively high suicide rate; continuing
      controversies in the pharmacological management of the disorder; and a
      potentially elevated cost-of-care contributed by the prescription of brand-name
      medications as well as laboratory monitoring at baseline and intermittently for
      lithium and atypical antipsychotics and serum levels for lithium and some
      anticonvulsants. All of these factors seem to result in an understandable
      hesitancy on the behalf of primary care clinicians to diagnose and assume care
      for these complex patients. Mental health professionals need to remain mindful of
      these issues when arranging dispositions for patients.

PMID- 22132366
TI  - Mood symptoms, cognition, and everyday functioning: in major depression, bipolar
      disorder, and schizophrenia.
AB  - People with depression, bipolar disorder, and schizophrenia manifest considerable
      cognitive deficits and impairments in everyday functional outcomes. The severity
      of current mood symptoms is associated with the severity of cognitive deficits in
      people with unipolar and bipolar disorder, but impairments are clearly still
      present in cases with minimal current mood symptoms. In people with
      schizophrenia, depression is less strongly associated with cognitive deficits on
      a cross-sectional basis, and some evidence suggests that depression and cognitive
      impairments are inversely related. Furthermore, in schizophrenia, mood symptoms
      seem to affect everyday functioning in a way that is unassociated with the
      severity of deficits in cognition and functional capacity. In contrast, in
      bipolar disorder, mood symptoms seem to affect real-world functioning through an
      adverse effect on the ability to perform critical functional skills. In both mood
      disorders and schizophrenia, depression appears to impact the motivation to
      perform potentially reinforcing acts, possibly through the induction of
      anhedonia. Clearly, depression has a major adverse impact on everyday functioning
      in all variants of severe mental illness, and improving its recognition (in the
      case of schizophrenia) and management has the potential to reduce the adverse
      impact of severe mental illness on everyday functioning. Reducing disability has
      the potential to have positive impacts in multiple objective and subjective
      aspects of functioning in severe mental illness.

PMID- 22132367
TI  - Use of a relapse monitoring board: an independent assessment for determining
      relapse in clinical trials for bipolar disorder.
AB  - OBJECTIVE: Independent review boards can provide an objective appraisal of
      investigators' decisions and may be useful for determining complex primary
      outcomes, such as bipolar disorder relapse, in crossnational studies. This
      article describes the use of an independent, blinded relapse monitoring board to
      assess the primary outcome (relapse) in an international clinical trial of
      risperidone long-acting therapy adjunctive to standard-care pharmacotherapy for
      patients with bipolar disorder. DESIGN: The fully autonomous relapse monitoring
      board was composed of a chair and two additional members-all psychiatrists and
      experts in the diagnostic, clinical, and therapeutic management of bipolar
      disorder. The relapse monitoring board met six times during the study to review
      patient relapse data and was charged with the responsibility of determining if
      the events described by investigators qualified as relapses. Additionally, the
      relapse monitoring board reviewed data for all randomized patients to identify
      any relapse events not recognized by investigators. RESULTS: Primary efficacy
      results were similar and significant for investigator- and relapse monitoring
      board-determined relapses. Ten discrepancies were noted: two of the 42
      investigator-determined relapses did not meet the intended clinical relapse
      threshold as determined by the relapse monitoring board; conversely, the relapse
      monitoring board confirmed eight relapse events not identified by investigators.
      The relapse monitoring board had no direct interactions with patients and had to
      rely on the accuracy of investigator assessments. Also, once an investigator
      determined a relapse and the patients discontinued the study, less information
      was available to the relapse monitoring board for relapse assessment.
      CONCLUSIONS: Use of the relapse monitoring board supported the validity of the
      study by incorporating a level of standardization to mitigate the risk that local
      practice in different cultures and medical systems at the sites would confound
      study results.

PMID- 22132368
TI  - Insight into delirium.
AB  - Delirium is a common and serious disorder with high morbidity and mortality. It
      occurs in 35 to 80 percent of critically ill, hospitalized patients. It may lead
      to mortality if not detected early. Studies show that delirium causes death in as
      many as 22 to 76 percent of patients who are hospitalized with delirium. It is
      often unrecognized and inadequately treated, and this may lead to poor outcome,
      including long-term care, longer length of stay in hospital, and high impact on
      health and social expenditure. There may be many reasons that delirium goes
      undetected, such as not understanding full pathophysiology and not having enough
      diagnostic tools to detect delirium in the early phase. A clear understanding of
      neurochemical equilibrium and pathways of the brain will help the clinician to
      understand the signs and symptoms of delirium. Pathophysiology of delirium is
      complex, and multiple theories have been proposed to explain its exact
      pathophysiology, but none of these mechanisms have been fully understood. Early
      detection of delirium and reduction of modifiable risk factors, along with better
      management, can result in better outcomes. This article discusses the
      pathophysiology and parts of brain involved in delirium as well as mood and
      psychotic symptoms of delirium.

PMID- 22132369
TI  - Kleptomania and potential exacerbating factors: a review and case report.
AB  - Kleptomania is an impulse control disorder that can cause significant impairment
      and serious consequences. Often, the condition is kept secret by the patient, and
      usually help is sought only when confronted by the legal consequences of the
      impulsive behaviors. Historically, kleptomania has been viewed from a
      psychodynamic perspective, and the mainstay of treatment has been psychotherapy.
      Recently, attempts to explain kleptomania within a neuropsychiatric paradigm have
      highlighted the possible links between mood disorders, addictive behaviors, and
      brain injury with kleptomania. These associations with kleptomania can be
      extrapolated to pharmacological strategies that can potentially help in treating
      kleptomania. A case of kleptomania, which was potentially exacerbated by multiple
      factors, will be reviewed. Treatment modalities used in this case, including the
      use of the Yale-Brown Obsessive Compulsive Scale as a surrogate marker to gauge
      response to treatment, will be discussed.

PMID- 22132370
TI  - Fatigue as a residual symptom of depression.

PMID- 22132372
TI  - Purification and characterization of a heteromultimeric glycoprotein from
      Artocarpus heterophyllus latex with an inhibitory effect on human blood
      coagulation.
AB  - Plant latex has many health benefits and has been used in folk medicine. In this
      study, the biological effect of Artocarpus heterophyllus (jackfruit) latex on
      human blood coagulation was investigated. By a combination of heat precipitation
      and ion-exchange chromatography, a heat stable heteromultimeric glycoprotein
      (HSGPL1) was purified from jackfruit milky latex. The apparent molecular masses
      of the monomeric proteins on SDS/PAGE were 33, 31 and 29 kDa. The isoelectric
      points (pIs) of the monomers were 6.63, 6.63 and 6.93, respectively.
      Glycosylation and deglycosylation tests confirmed that each subunit of HSGPL1
      formed the native multimer by sugar-based interaction. Moreover, the multimer of
      HSGPL1 also resisted 2-mercaptoethanol action. Peptide mass fingerprint analysis
      indicated that HSGPL1 was a complex protein related to Hsps/chaperones. HSGPL1
      has an effect on intrinsic pathways of the human blood coagulation system by
      significantly prolonging the activated partial thrombin time (APTT). In contrast,
      it has no effect on the human extrinsic blood coagulation system using the
      prothrombin time (PT) test. The prolonged APTT resulted from the serine protease
      inhibitor property of HSGPL1, since it reduced activity of human blood
      coagulation factors XI(a) and alpha-XII(a).

PMID- 22132371
TI  - Secretion of proinflammatory cytokines by normal human melanocytes in response to
      lipopolysaccharide.
AB  - A large body of evidence suggests that epidermal melanocytes are an integral part
      of the skin immune system and can be considered immunocompetent cells. Recently,
      it has been reported that human melanocytes constitutively express Toll-like
      receptors and may be involved in the induction of several inflammatory cytokines.
      In the study the secretion of IL-1beta, IL-6 and TNF-alpha by cultured normal
      melanocytes was investigated after stimulation with lipopolysaccharide. LPS
      increased the secretion of IL-1beta in a dose-dependent manner. IL-1beta
      stimulated release of IL-6 and TNF-alpha by melanocytes, whereas LPS activated
      production of TNF-alpha, but not of IL-6. These observations indicate that LPS
      can participate in the regulation of cytokine activity in normal human
      melanocytes and suggest that cytokines released by melanocytes could affect
      melanocytes themselves or/and other cells of the epidermis.

PMID- 22132373
TI  - Differences in glutathione S-transferase pi expression in transgenic mice with
      symptoms of neurodegeneration.
AB  - Glutathione S-transferase pi (GST pi) is an enzyme involved in cell protection
      against toxic electrophiles and products of oxidative stress. GST pi expression
      was studied in transgenic mice hybrids (B6-C3H) with symptoms of
      neurodegeneration harboring SOD1G93A (SOD1/+), Dync1h1 (Cra1/+) and double
      (Cra1/SOD1) mutations, at presymptomatic and symptomatic stages (age 70, 140, 365
      days) using RT-PCR and Western blotting. The main changes in GST pi expression
      were observed in mice with the SODG93A mutation. In SOD1/+ and Cra1/SOD1
      transgenics, with the exception of cerebellum, the changes in GST pi-mRNA
      accompanied those in GST pi protein. In brain cortex of both groups the
      expression was unchanged at the presymptomatic (age 70 days) but was lower at the
      symptomatic stage (age 140 days) and at both stages in hippocampus and spinal
      cord of SOD1/+ but not of Cra1/SOD1 mice compared to age-matched wild-type
      controls. In cerebellum of the presymptomatic and the symptomatic SOD1/+ mice and
      presymptomatic Cra1/SOD1 mice, the GST pi-mRNA was drastically elevated but the
      protein level remained unchanged. In Cra1/+ transgenics there were no changes in
      GST pi expression in any CNS region both on the mRNA and on the protein level. It
      can be concluded that the SOD1G93A but not the Dync1h1 mutation significantly
      decreases detoxification efficiency of GST pi in CNS, however the Dync1h1
      mutation reduces the effects caused by the SOD1G93A mutation. Despite
      similarities in neurological symptoms, the differences in GST pi expression
      between SOD1/+ and Cra1/+ transgenics indicate a distinct pathogenic entity of
      these two conditions.

PMID- 22132374
TI  - Different statins produce highly divergent changes in gene expression profiles of
      human hepatoma cells: a pilot study.
AB  - Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the
      key enzyme of the sterol biosynthesis pathway. Statin therapy is commonly
      regarded as well tolerated. However, serious adverse effects have also been
      reported, especially during high-dose statin therapy. The aim of our study was to
      investigate the effect of statins on gene expression profiles in human hepatoma
      HepG2 cells using Affymetrix Human Genome U133 Plus 2.0 arrays. Expression of
      102, 857 and 1091 genes was changed substantially in HepG2 cells treated with
      simvastatin, fluvastatin and atorvastatin, respectively. Pathway and gene
      ontology analysis showed that many of the genes with changed expression levels
      were involved in a broad range of metabolic processes. The presented data clearly
      indicate substantial differences between the tested statins.

PMID- 22132375
TI  - An eclectic issue.

PMID- 22132376
TI  - Understanding the prevalence of long-term conditions.

PMID- 22132377
TI  - I suggest you take up some exercise like running.

PMID- 22132378
TI  - Can the prevalence of diagnosed diabetes be estimated from linked national health
      records? The validity of a method applied in New Zealand.
AB  - INTRODUCTION: With projected global increases in the prevalence of Type 2
      diabetes, the health sector requires timely assessments of the prevalence of this
      disease to monitor trends, plan services, and measure the efficacy of prevention
      programmes. AIM: To assess the validity of a method to estimate the prevalence of
      diagnosed diabetes from linked national health records. METHODS: We measured the
      agreement between a diabetes diagnosis (using combined national lists of drug
      dispensing, outpatient attendance, laboratory tests (HbA1c) and hospital
      diagnoses) and a primary care diabetes diagnosis in a (PREDICTTM) cohort of
      53,911 adult New Zealanders. The completeness of the diagnosis of diabetes in the
      cohort was estimated using capture-recapture methods. RESULTS: The primary care
      cohort had a high prevalence of recorded diabetes (20.9%, 11,266/53,911), similar
      to our derived prevalence of 20.1%. Of the participants with a diagnosis of
      diabetes, 89% (10,182/11,266) had a similar derived diagnosis, indicating that
      only about one in 10 people with a primary care diagnosis had not been either
      admitted to hospital, seen at outpatient clinics, prescribed diabetes drugs or
      undertaken regular HbA1c tests. The capture-recapture prevalence of diagnosed
      diabetes in this cohort was 23.7% indicating that primary care diagnoses in the
      cohort were about 90% complete. DISCUSSION: A method for estimating the
      prevalence of diagnosed diabetes from national health data shows high-level
      agreement with primary care records. Linked health data can provide an efficient
      method for estimating the prevalence of diagnosed diabetes in regions where such
      records are individually linked.

PMID- 22132379
TI  - Randomised controlled trial of informal team sports for cardiorespiratory fitness
      and health benefit in Pacific adults.
AB  - INTRODUCTION: Rates of obesity, Type 2 diabetes and cardiovascular disease are
      high among Pacific people in New Zealand. Physical activity is recommended in the
      prevention and management of these conditions. Community-based, 'small-sided
      game' group activities may be an effective and culturally appropriate way to
      promote physical activity within Pacific communities. AIM: To assess the
      effectiveness of small-sided games-based exercise on fitness and health
      parameters among Pacific adults over four weeks. METHODS: Twenty untrained (13
      female) Pacific adults were randomised to intervention or control. Intervention
      participants were offered 45 minutes of small-sided games three times per week
      for four weeks. Control participants were offered one-month gym membership after
      the trial. Primary outcomes included cardiorespiratory fitness (VO2peak) and leg
      strength (maximal concentric force of quadriceps at 60 degrees /second) measured
      at baseline and four weeks. Secondary outcomes included glycaemia, lipid profile,
      blood pressure (BP), and inflammatory markers. Multivariable regression models
      were used to assess differences between groups, adjusting for baseline values,
      age and gender. RESULTS: At baseline, mean age was 34.8 years (SD 12.6), BMI 36.3
      (6.7), systolic BP 127.7 mmHg (12.1), HbA1c 6.1% (1.9), VO2peak 2.5 L/min (0.6)
      and leg strength 170.0 N.m (57.4). Sixteen participants completed the trial.
      Change in outcomes were greater in intervention than control participants in
      absolute VO2peak (0.9 L/min (p=0.003)), leg strength (17.8 N.m (p=0.04)) and HDL
      (0.12 mmol/L (p=0.02)). There were no other significant differences. DISCUSSION:
      Small-sided games appear to be a promising means for improving the health and
      cardiorespiratory fitness and reducing the risk of diabetes and cardiovascular
      disease in Pacific adults.

PMID- 22132380
TI  - Assessing the effectiveness of cold chain management for childhood vaccines.
AB  - INTRODUCTION: Effective immunisation programmes require a stable cold chain to
      maintain potency of vaccines from national stores through to delivery sites. AIM:
      To assess the effectiveness of the New Zealand cold chain and examine the
      possible impacts of policy changes over the same time period on cold chain
      effectiveness. METHODS: Heat- and freeze-sensitive monitors were attached to 5%
      of randomly selected childhood vaccines from 2002 to 2008. Six-monthly reports on
      data collected from monitor cards were collated and analysed to look for changes
      over time in freeze and heat exposure failures for vaccines. RESULTS: From
      December 2002 to June 2008 a total of 21,431 monitor cards were included in
      vaccines distributed from the national store; 9474 (44.2%) of all cards were
      returned and 8249 (38.5% of total) were correctly completed. Over this period the
      percentage of valid returns recorded as heat exposed decreased from 38% to 7%
      (chi2 371, p<0.001); heat failures decreased from 3% to 0.3% (chi2 371,
      p<0.0001); freeze failures decreased from 16% to 2% (chi2 134.228, p<0.0001), and
      overall wastage from 17% to 2% (chi2 163.83, p<0.0001), giving estimated annual
      savings of nearly NZ$4 million. DISCUSSION: Significant improvements can be made
      in cold chain management with resulting savings in vaccine wastage. This study
      demonstrates that such improvements have been made in New Zealand in recent
      years. This is likely to be due to a combination of improving equipment, systems,
      education and training, increased provider attention and quality standards.

PMID- 22132381
TI  - Tax as a motivating factor to make a quit attempt from smoking: a study before
      and after the April 2010 tax increase.
AB  - INTRODUCTION: Increasing excise tax on tobacco is one of the most powerful and
      cost-effective smoking interventions. Despite this evidence, there has been no
      substantial tax increase in New Zealand between 2000 and 2010. In April 2010 a
      10% tax increase on factory-made cigarettes and a 24% tax increase on loose leaf
      tobacco was implemented. AIM: To evaluate the effect of cost as a motivating
      reason for smokers to make a quit attempt before and after the 2010 tobacco tax
      increase. METHODS: A regression analysis of a cross-sectional study was
      conducted. Data were collected from August to October 2009 and compared with data
      collected in July 2010. RESULTS: In 2009, 25.5% of smokers cited cost as a reason
      for trying to quit smoking compared with 55.6% in 2010. The adjusted odds of
      making a quit attempt with cost as a reason were 3.6 (95% CI 2.3-5.6, P =
      <0.001). Furthermore, smokers were more likely to make a quit attempt in 2010
      than in 2009. Thirty percent of smokers made at least one quit attempt in 2009
      and 39% made a quit attempt in 2010 (adjusted odds ratio 1.5, 95% CI 0.95-2.3, P
      = <0.1) DISCUSSION: The recent tax increase on tobacco in New Zealand has
      resulted in more smokers making an attempt to quit smoking and more smokers
      identifying cost as a motive for quitting.

PMID- 22132382
TI  - Nurses' perceptions of nurse-led healthy lifestyle clinics.
AB  - INTRODUCTION: Nineteen Nurse-Led Healthy Lifestyle Clinics (NLHLCs) were
      implemented and targeted Maori, Pacific and people living in high deprivation
      areas. The general focus of the clinics was on lifestyle issues and much of the
      nursing was educative and preventative care. The aim of this project was to
      assess nurses' experiences and opinions of their participation in the clinics.
      METHODS: Nurses participating in the clinics were asked to complete a monthly
      narrative report over five reporting periods, and these were collated and
      evaluated for emergent themes. Sixteen nurses were subsequently interviewed and
      the transcripts analysed to identify major themes and sub-themes. FINDINGS: In
      total, 167 narrative reports were collected from 53 of the 115 participating
      nurses. Almost all the nurses either strongly agreed or agreed that they enjoyed
      working in an NLHLC. This enjoyment was the result of: increased time for in
      depth consultations, being able to provide enhanced holistic patient care,
      developing knowledge, gaining experience, receiving positive patient feedback and
      the satisfaction of seeing patient improvements. Nurses reported that the
      opportunity and responsibility of providing holistic nursing care, and the skills
      and knowledge gained from participating in the project, were extremely valuable.
      CONCLUSION: NLHLCs provide benefits for both patient and nurse. For the nurse,
      job satisfaction is increased through positive patient feedback, opportunities
      for professional development and a greater feeling of empowerment.

PMID- 22132383
TI  - Clinical teachers working in primary care: what would they like changed in the
      medical school?
AB  - INTRODUCTION: General practitioners (GPs) working as clinical teachers are likely
      to influence medical students' level of community-based learning. This paper
      aimed to ascertain clinical teachers' views in relation to The University of
      Auckland about their clinical learning environment. METHOD: A total of 34
      clinical teachers working in primary care contributed to this study. To gauge
      their level of involvement in teaching and learning, the clinical teachers were
      asked about issues such as their confidence, available time, sufficient clinical
      learning opportunities, clear learning objectives to teach students and what they
      would like changed. FINDINGS: The GPs appeared confident, felt there were
      sufficient learning opportunities for students and that their students were part
      of the team. Less experienced teachers expressed less confidence than more
      experienced peers. There was some hesitancy in terms of coping with time and
      feedback. Some clinical teachers were unclear about the learning objectives
      presented to students. CONCLUSION: Several issues that emerged--including
      available time and financial rewards--are difficult to resolve. Curriculum and
      selection are evolving issues requiring constant monitoring and alignment with
      increasing numbers of students studying medicine, increased ethical awareness,
      more diverse teaching systems and more advanced technologies. Non-faculty
      clinicians need adequate representation on curriculum committees and involvement
      in clinical education initiatives. Issues of cultural competency and professional
      development were raised, suggesting the need for more established links between
      university and GPs.

PMID- 22132384
TI  - Patient Dashboard: the use of a colour-coded computerised clinical reminder in
      Whanganui regional general practices.
AB  - INTRODUCTION: Clinical reminders have been shown to help general practice achieve
      an increase in some preventive care items, especially if they identify a
      patient's eligibility for the target item, prompt clinicians at the right time,
      provide a fast link to management tools and facilitate clinical recording. WRPHO
      has introduced the Patient Dashboard clinical reminder and monitored its impact
      on health targets. AIM: This paper reports the impact of a computerised colour
      coded clinical reminder on achieving agreed health targets in Whanganui regional
      practices. METHODS: Patient Dashboard was developed from previous versions in
      Auckland and Northland and provided to Whanganui regional practices with Primary
      Health Organisation (PHO) support. The Dashboard was linked with existing and new
      clinical management tools which automatically updated clinical records. Data from
      practices was pooled by Whanganui Regional Primary Health Organisation and target
      achievement rates reported over 15 months. RESULTS: Over the initial 15 months of
      Patient Dashboard use, recording of smoking status increased from 74% to 82% and
      of alcohol use from 15% to 47%. Screening for diabetes increased from 62% to 74%,
      cardiovascular risk assessment from 20% to 43%, cervical screening from 71% to
      79%, and breast screening from 60% to 80%. DISCUSSION: Patient Dashboard was
      associated with increased performance indicators both for those targets which
      were part of a PHO programme and for targets without additional support.

PMID- 22132385
TI  - A Pacific immersion programme--is it useful in teaching Pacific health to future
      doctors in New Zealand?
AB  - BACKGROUND AND CONTEXT: Pacific peoples make up approximately 7% of the total
      population in New Zealand, and are over-represented in poor health statistics.
      There are very few Pacific peoples in the health workforce. Most Pacific patients
      will be seen by a non-Pacific health professional when seeking medical care. It
      is important for all health education institutions, therefore, to include Pacific
      health as part of their curricula. ASSESSMENT OF PROBLEM: This article outlines
      the development and evaluation of a Pacific immersion programme to teach medical
      students about Pacific health. The programme was developed with the assistance of
      local Pacific community leaders. Learning objectives for students, protocols and
      processes were developed. These learning objectives and feedback from medical
      students, staff and host families, formed the basis for evaluating the programme.
      RESULTS: Students found the programme to be very useful. Host families were
      satisfied with the experience. Staff support ensured the programme became a
      required part of learning at the Dunedin School of Medicine. STRATEGIES FOR
      IMPROVEMENT: The pilot programme was initially offered as an optional choice for
      students. In the future, all students at the Dunedin School of Medicine will be
      expected to undertake the programme. A research project looking at changes in
      knowledge, skills and attitudes of students after the programme will be of value.
      LESSONS: The programme provided a useful way for teaching Pacific health to
      undergraduate medical students. Other institutions could consider this method for
      teaching Pacific health in their curricula.

PMID- 22132386
TI  - Saturated fat has been unfairly demonised: yes.

PMID- 22132387
TI  - Saturated fat has been unfairly demonised: no.

PMID- 22132388
TI  - Aloe vera--Aloe vera, Aloe barbadensis, Aloe capensis.

PMID- 22132389
TI  - e Runanga o Te Rarawa rheumatic fever reduction progamme--Kaitaia.

PMID- 22132390
TI  - Alliance Health+ Trust.

PMID- 22132391
TI  - A tale of two deaths.

PMID- 22132392
TI  - Tranexamic acid--a recipe for saving lives in traumatic bleeding.

PMID- 22132393
TI  - Getting to the pharmacy: auditing primary non-adherence.

PMID- 22132394
TI  - The importance of locality planning in New Zealand health care.

PMID- 22132395
TI  - Access-literacy gap in online health education for diabetes--Internet access is
      just one link.

PMID- 22132396
TI  - Is there a place of contrast-enhanced ultrasonography in deep vein thrombosis?

PMID- 22132397
TI  - Contrast Enhanced Ultrasound of the lower limb deep venous system: a technical
      feasibility study. Technical innovation.
AB  - BACKGROUND: A clear diagnosis of deep venous thrombosis (DVT) is still
      challenging: many patients with unclear compression/duplex-sonography undergo a
      trial of anticoagulative treatment with the immanent risk of systemic hemorrhagic
      complications. As contrast enhanced ultrasound (CEUS) has the potential to
      visualize the blood pool, we conducted this pilot study to determine its
      potential in the characterization of the deep venous system of the lower limb.
      MATERIAL AND METHODS: CEUS was performed with a 9-3 MHz broadband linear
      transducer (iU22(r), Philips, USA) after the standard-application of a second
      generation contrast agent (SonoVue(r), Bracco, Italy) in three healthy
      volunteers. Transverse US-scans were performed for depiction of the fibular-,
      posterior tibial-vein group, the popliteal, femoral, the external iliacal and the
      inferior caval vein at defined levels. RESULTS: On our three volunteers the
      intended segments of the deep venous system of the lower limb were visualized
      clearly between 45 and 350 seconds by CEUS. The continuous proximal ward scanning
      demonstrated the venous topography up to the external iliac veins. DISCUSSION AND
      CONCLUSIONS: These preliminary results show that the use of CEUS is at least
      promising in the detection and characterization of the deep venous system of the
      lower limb. This should be pathbreaking, especially in patients with e.g. high
      Body Mass Index, local edema, diffuse inflammation etc. undergoing sonographic
      assessment for suspected deep vein thrombosis not definable by complete
      compression venous ultrasound or duplex ultrasound.

PMID- 22132398
TI  - Ultrasonographic findings of intussusception in pediatric cases.
AB  - PURPOSE: We aimed to characterize, by ultrasonography (US), the aspects,
      locations and the dimensions of intussusceptions in pediatric cases and to
      compare these data with the clinical findings and therapeutical outcomes.
      MATERIALS AND METHODS: We retrospectively evaluated abdominal US examinations and
      clinical data of 13 consecutive pediatric patients with intussusceptions.
      Patients are grouped according to the type of intussusceptions (ileocolic
      intussusceptions and intussusceptions with colocolic involvement) and according
      to the modality of treatment (surgical and non-surgical). RESULTS: Median age was
      24 months (range 5-108 months). Eleven cases were surgically treated because of
      delayed referral.  For all cases the mean diameter+/-SD of intussusception was
      30+/-5 mm and mean length+/-SD was 59+/-21 mm. For ileocolic intussusceptions
      (n=9/11), mean diameter+/-SD was 29.1+/-4.4 mm and mean length+/-SD was 61.7+/
      18.1 mm. The right upper quadrant of abdomen was the most common location for
      ileocolic intussusceptions (n=7/9), the rest were located in paraumbilical
      regions (n=2/9). For two cases of intussusceptions with colocolic involvement
      (ileocolocolic and colocolic intussusceptions located in right upper quadrant and
      left lower quadrant, respectively), mean diameter+/-SD was 37.5+/-0.7 mm and mean
      length+/-SD was 75.5+/-21.9 mm. The difference between mean diameters of
      ileocolic intussusceptions and intussusceptions with colocolic involvement was
      statistically significant (p =0.03), whereas the difference between  mean lengths
      of these two groups was not statistically significant (p=0.36). For surgically
      treated cases (n=11/13), mean diameter+/-SD of intussusception was 30.6+/-5.2 mm
      and the mean length +/-SD was 64.2+/-18.5 mm. For non-surgically treated cases
      (n=2/13), with intussusceptions located in right lower quadrant, mean diameter+/
      SD of intussusception was 27+/-4.2 mm and the mean length+/-SD was 32.5+/-10.6
      mm. The difference between mean diameters of surgically and non-surgically
      treated cases was not statistically significant (p=0.37), whereas the difference
      between mean lengths of these two groups was statistically significant (p=0.04).
      CONCLUSIONS: A very good correlation between US and surgical findings was
      obtained. US should be used in all pediatric patients clinically suspected for
      intussusception. A relatively large, target-like and sandwich-like,
      incompressible intraabdominal bowel mass having the above mentioned dimensions
      should be looked for on US examination.

PMID- 22132399
TI  - Clinical, imaging and cystometric findings of voiding dysfunction in children.
AB  - The AIM of the study was to validate some of the imaging criteria for voiding
      dysfunction in children. MATERIAL AND METHODS: The study included a number of 55
      children with voiding dysfunction symptoms. They were investigated clinically as
      well as through imaging techniques: renourinary ultrasound, voiding
      cystourethrography and cystometry. RESULTS: The most common symptoms were urgency
      (87.3%), increased frequency (81.8%), and daytime urinary incontinence (76.3%).
      Ultrasound scans detected a reduced bladder capacity in 65.5% patients. The
      voiding cystourethrography detected bladder trabeculations (58.2%) and spinning
      top urethra (63.6%). Cystometric recordings indicated overactive bladder in 70.9%
      patients. Reduced bladder capacity detected by ultrasound associated with
      trabeculated bladder and spinning top urethra detected by voiding
      cystourethrography in a patient with specific symptoms may suggest an overactive
      bladder. In CONCLUSION, voiding dysfunction in child can be diagnosed by minimal
      or non-invasive methods.

PMID- 22132400
TI  - Medical education for emergency physician focused on basic competence (Focused
      Assessment with Sonography in Trauma). Evaluation of the Romanian national
      program: "Regional Emergency Medical Services Systems".
AB  - Focused Assessment with Sonography in Trauma (FAST), a type of training for
      unique ultrasonography competence, represents a necessity in the emergency
      assistance of the trauma patient. The principal OBJECTIVE of this prospective
      study was to evaluate the teaching performance and to identify the training
      necessities related to the curriculum of the unique ultrasonography competence-
      FAST--used in the frame of the national program of rehabilitation of the
      emergency system in Romania. MATERIAL AND METHOD: The study was performed on a
      number of 164 emergency medicine physicians, trained following a unique
      theoretical and practical curriculum, between April and December 2006 in 4
      Romanian university centers. RESULTS: The assessment of the theoretical knowledge
      acquired during the training program revealed a significant (p<0.0001)
      improvement. The comparative analysis of the theoretical evaluation results
      between the center in Cluj and the other three training centers did not show
      statistically significant differences. The differences were noticed at the level
      of the practical evaluation (p<0.005). The attendees observed the need for
      supplementing the practical activities in trauma emergency situations (57.38% 
      72.08%). CONCLUSIONS: The implementation of a national training program, with a
      unitary curriculum, creates premises for a standardized training process. The
      first national training program in FAST, a unique competence in emergency
      ultrasonography, identified the necessity for curricular remodeling.

PMID- 22132401
TI  - Nasal bone fracture--ultrasonography or computed tomography?
AB  - AIM: The aim of the study is to estimate the diagnostic sensitivity and utility
      of high-resolution ultrasonography (HRUS) in comparison with a gold standard
      technique in the diagnosis of the nasal fracture. PATIENTS AND METHOD: Using a
      retrospective study design, facial Computed Tomography (CT) and HRUS examinations
      were performed on 87 consecutive patients with nasal trauma. Ultrasonograms were
      obtained with a high frequency linear transducer (10 MHz). All patients also
      underwent facial conventional radiography (CR). The sensitivity and specificity
      for diagnosis of nasal fracture was evaluated for HRUS, CT and CR in comparison
      with the clinical examination. Then sensitivity and specificity of HRUS and CR
      were evaluated in comparison with CT. RESULTS: The sensitivity and specificity of
      HRUS, CT and CR in comparison with clinical exam in the diagnosis of nasal bone
      fracture was 97% and 100%, 86% and 87%, 72% and 73% respectively. The sensitivity
      and specificity of HRUS and CR in detecting fracture line in comparison with CT
      was 100% respectively 91%, and 79% respectively 95%. CONCLUSION: HRUS is a
      reliable and available method for diagnosis of nasal bone fractures especially in
      the fracture, which is confined to the nasal bone and can be used as a modality
      of choice for investigation of nasal fracture.

PMID- 22132402
TI  - Contrast-enhanced ultrasonography with intraarterial administration of SonoVue
      for guidance of transarterial chemoembolization: an initial experience.
AB  - AIMS: To describe the technique and to evaluate the feasibility of contrast
      enhanced ultrasound with intraarterial administration of echo-enhancer (i.a CEUS)
      as a method for guidance of transarterial chemoembolization (TACE). PATIENTS AND
      METHODS: Twelve patients with 17 target liver tumors underwent superselective
      TACE, guided with i.a CEUS. After microcatheter placement in a (sub)segmental
      artery suspected as a tumor feeder, a diluted suspension of SonoVue was injected
      through the microcatheter, and imaging of the target tumor was performed with a
      low mechanical index technique and with contrast-specific software. If
      intraarterial injection of SonoVue was associated with immediate, strong tumoral
      enhancement, the injected artery was considered as tumor-feeding and TACE was
      performed, otherwise another artery was evaluated. RESULTS: From 25 segmental or
      subsegmental arteries evaluated i.a CEUS confirmed that 16 arteries were actually
      tumor feeders and unequivocal excluding  4 arteries as a tumor arterial supply.
      The remainder 5 arterial branches could not be safely characterized due to
      artifacts or technical limitations. In 8 patients in which tumoral vascular
      supply could not be elucidated by angiography alone, i.a CEUS increased the
      accuracy of supereselective embolization, and provided other clinically relevant
      information in 2 of these patients. No adverse effects were observed.
      CONCLUSIONS: For guidance of superselective TACE i.a CEUS is a safe and feasible
      method..

PMID- 22132403
TI  - Transabdominal ultrasound in inflammatory bowel disease. Conventional and
      recently developed techniques--update.
AB  - Transabdominal ultrasound is clinically useful in detecting Crohn's disease
      (initial diagnosis) by evaluating bowel wall thickness and surrounding structures
      including periintestinal inflammatory reaction, extent and localization of
      involved bowel segments and detection of extraluminal complications such as
      fistula, abscesses, carcinoma and ileus. Transabdominal ultrasound presently is
      accepted as a clinically important first line tool in assessing patients with
      Crohn's disease irrespective of their clinical symptoms and/or disease activity.
      It helps to better characterize the disease course in individual patients and can
      guide therapeutic decisions. In this review the current literature will be
      analysed.

PMID- 22132404
TI  - Hypoxic ischemic cerebral lesions of the newborn--ultrasound diagnosis. Pictorial
      essay.
AB  - Transcranial ultrasonography is the most widely used neuroimaging technique in
      both premature and full term infants. The high susceptibility to hypoxia of the
      preterm brain explains the raised prevalence of intracranial haemorrhages at this
      group of patients.  Ultrasound examination contributes to assessment of the
      neurologic status in children by diagnosing and staging of the intracranial
      bleeding, and brings informations about immediate and long term prognosis. The
      two major pictures of cerebral damage secondary to perinatal hypoxia are: peri
      and intraventricular haemorrhages and periventricular leucomalacia respectively.
      This paper present the major features for ultrasound diagnosis in  both
      pathological situations.

PMID- 22132405
TI  - Bilateral Achilles tendon ossification: diagnosis with ultrasonography and Single
      Photon Emission Computed Tomography/Computed Tomography. Case report.
AB  - Ossification of the Achilles tendon is a rare clinical condition characterized by
      the presence of one or more segments of variable sized ossified mass within the
      tendon. The cause of the condition is obscure. We present the case of a 41 year
      old male patient with pain in the Achilles tendon due to bilateral ossification
      of the tendon near the calcaneus insertion.  The case was evaluated by
      ultrasonography, single photon emission computed tomography, and transmission
      computed tomography. In this case, we regarded repetitive microtrauma as the
      cause of the ossification based on the bilateral occurrence.

PMID- 22132406
TI  - Rupture sinus of Valsalva in a patient with dextrocardia. Case report.
AB  - Ruptured sinus of Valsalva (RSOV) is a rare disease with a wide range of clinical
      manifestations, from asymptomatic murmur to cardiogenic shock and death. We
      present the case of a young woman known with dextrocardia and pulmonary agenesia;
      she was diagnosed with RSOV and during follow-up, with endocarditis. Her
      evolution was good despite the association of severe heart conditions and the
      refusal of surgical intervention.

PMID- 22132407
TI  - Carotid ultrasound.
AB  - Carotid duplex ultrasonography is a noninvasive technique for hemodynamically
      significant stenosis detection and cardiovascular risk estimation. Anatomic
      information of carotid arteries is provided by B-mode scanning. Hemodynamic
      features are displayed color-flow and pulsed Doppler imaging. Examination
      technique, normal carotid anatomy and flow pattern, and potential limitations are
      presented.

PMID- 22132408
TI  - Bleeding umbilical nodule.

PMID- 22132409
TI  - Romanian ultrasonography in Viena.

PMID- 22132410
TI  - Project on the use of ultrasonography as a support tool for the study of medical
      semeiology at the Faculty of Medicine in Cluj-Napoca.

PMID- 22132413
TI  - Mediator free cholesterol biosensor based on self-assembled monolayer platform.
AB  - Self-assembled monolayer (SAM) of 4-aminothiophenol (4-ATP) has been investigated
      for immobilization of bi-enzymes (ChOx and ChEt) towards development of enzyme
      biosensors for detection of free and total cholesterol. This enzyme immobilized
      SAM surface has been characterized by scanning electron microscopy and
      electrochemical measurements. The results of electrochemical response studies
      reveal fast enzymatic reaction in phosphate buffer saline solution without using
      any artificial mediator. This may be attributed to the molecular wire type
      behavior of short 4-ATP molecule that promotes electron transfer between enzyme
      and the electrode surface due to its conjugated structure. Interference free
      estimation of free and total cholesterol has been realized at low operating
      potential of 0.33 V with range of detection as 25 to 400 mg dl(-1), sensitivity
      of 542.3 nA mM(-1) (for ChOx/4-ATP/Au) and 886.6 nA mM(-1) (for ChEt-ChOx/4
      ATP/Au) with a response time of 20 s at pH 7.4.

PMID- 22132412
TI  - A general chemical synthesis platform for crosslinking multivalent single chain
      variable fragments.
AB  - Multivalent single chain variable fragments (scFv) show increased affinity to
      tumor-associated antigens compared to monovalent scFv and intact monoclonal
      antibodies (mAb). Multivalent constructs can be derived from self-associating or
      covalent scFv with covalent constructs offering improved in vivo and in vitro
      stability. Covalent attachment of scFv can be achieved using genetically
      engineered expression vectors that afford scFv with site specific cysteine
      functionality. Expression vectors for di-scFv-C wherein the cysteine is located
      in the center of two scFv have also been developed for attaching chemically
      reactive linkers. In the example illustrated here, the di-scFv-C is derived from
      a mAb directed against the MUC1 epitope, which is presented on cancer cells. To
      achieve multivalency, a chemical crosslinking strategy utilizing various azide
      and multi-alkyne functionalized polyethylene glycol (PEG) linkers was
      implemented. Conjugation was achieved by attachment of these linkers to the scFv
      thiol functionality. Chemoselective ligation was employed to covalently link
      different protein conjugates via copper(I) catalyzed azide alkyne 1,3-dipolar
      cycloaddition reaction (CuAAC) chemistry. Ligations were achieved in >70% yield
      using a specific set of linkers as determined by SDS-PAGE and densitometry. ELISA
      showed increased tumor binding of a tetravalent scFv providing a versatile
      chemical crosslinking strategy for construction of multivalent and bi-specific
      immunoconjugates that retain biological activity and have potential application
      in pre-targeted radioimmunotherapy and imaging.

PMID- 22132414
TI  - Detecting trace amounts of water in hydrocarbon matrices with infrared fiberoptic
      evanescent field sensors.
AB  - Water is a common contaminant in a variety of industrial oils and petroleum
      products. Thus, the detection of water in these products is of substantial
      relevance. Hence, this study focuses on quantifying trace amounts of water in
      hydrocarbons using hexane as a model system for industrial oils and petroleum
      matrices via mid-infrared (MIR) evanescent field absorption spectroscopy. A
      silver halide fiberoptic waveguide was used to interrogate in situ water-in
      hexane emulsions. Either unmodified fibers or waveguides surface-modified with
      polyacrylic acid layers were used. The limits of detection (LOD) and limits of
      quantification (LOQ) of water in hexane utilizing tin-crosslinked polyacrylic
      acid modified fibers were 76 and 170 ppm, respectively. Consequently, the IR
      absorption signature of water in hexane is detectable at concentrations as low as
      10 ppm. The proposed fiberoptic sensing strategy requires a single measurement
      only, requires no sample preparation, and thus has potential for the direct in
      situ detection and monitoring of water in industrial oils and petroleum products.

PMID- 22132415
TI  - How to keep track of one's physical activity budget using pervasive technologies.

PMID- 22132416
TI  - Re: Expending our physical activity (measurement) budget wisely.

PMID- 22132417
TI  - Emerging trends in estimating energy expenditure.

PMID- 22132418
TI  - Persistent left superior vena cava as cause of mediastinal widening.

PMID- 22132419
TI  - A wise (measurement) budget includes both increased precision and large sample
      size.

PMID- 22132420
TI  - The UN Summit and beyond: a new era for diabetes.

PMID- 22132421
TI  - Reversibility of spur cell anemia.

PMID- 22132422
TI  - Surrogate decision making: a woman in fulminant liver failure after an
      acetaminophen overdose.

PMID- 22132423
TI  - ROSC or death: some EMS systems stop transporting cardiac arrest patients,
      perform CPR at scene, roadside, ambulance bay.

PMID- 22132424
TI  - Autologous CCR5-modified CD4 T-cells effective in HAART nonresponders.

PMID- 22132425
TI  - Notice of retraction.

PMID- 22132435
TI  - The breast density--breast cancer connection.  Women whose breasts appear dense
      on mammograms have a higher risk for some aggressive breast cancers.

PMID- 22132436
TI  - How to get rid of warts.  Ugly and annoying, warts never seem to go away fast
      enough.  Treating them may help speed their departure.

PMID- 22132437
TI  - Update on vibration therapy for bone health.  Can gentle vibration improve bone
      density and prevent fractures after menopause?

PMID- 22132438
TI  - An antidote to bed rest?

PMID- 22132439
TI  - Novel foot-health program reduces falls in older people.

PMID- 22132440
TI  - Regular exercise may ward off cognitive decline in women with vascular disease.

PMID- 22132441
TI  - Ask the doctor. I have pain from osteoarthritis in both knees. I'm curious about
      the cream made from a substance in hot peppers. How does it relieve pain?

PMID- 22132442
TI  - Ask the doctor.  I'm 75 years old and healthy.  My doctor is still recommending
      annual Pap tests for me.  I have no history of any problems in this area and have
      had normal Pap tests for years.  Is this necessary at my age?

PMID- 22132443
TI  - Some comparative aspects of the fibrinogen-fibrin conversion.

PMID- 22132444
TI  - The sequence of amino acids at the N-terminal end of bovine fibrinopeptide B.

PMID- 22132445
TI  - Amino acid sequence studies on fibrinopeptides from several species.

PMID- 22132446
TI  - Hospitalization costs of pediatric bipolar disorder.

PMID- 22132447
TI  - Taiwanese researchers develop new  synthetic method for longer  a-oligosialic
      acids.

PMID- 22132448
TI  - Seattle Genetics announces collaboration with  Oxford BioTherapeutics.

PMID- 22132449
TI  - Obama signs America Invents Act.

PMID- 22132450
TI  - RNA editing: breaking the dogma.

PMID- 22132451
TI  - [Abstracts of the 61st General Meeting of the Japanese Society of Allergology.
      November 10-12, 2011. Tokyo, Japan].

PMID- 22132452
TI  - [Abstract of the 2011 joint meeting of the Japanese Medical Society of Alcohol
      and Drug Studies. Nagoya, Japan. October 13-15, 2011. ].

PMID- 22132453
TI  - [Abstracts of the 41st Easter/Western Regional Meeting, Japanese Society of
      Nephrology. 2011. Japan].

PMID- 22132454
TI  - [Abstracts of the 73 rd Annual Meeting of the Japanese Society of Hematology.
      October 14-16, 2011. Nagoya, Japan].

PMID- 22132455
TI  - The connection between endodontic treatment, dental implants, and neuropathy.

PMID- 22132456
TI  - [Day surgery for nasal obstruction--excluding that on the lower nasal turbinate].

PMID- 22132457
TI  - The diagnosis of art: Durer's squint - and Shakespeare's?

PMID- 22132458
TI  - Mental health is Europe's largest health challenge in the 21st century.

PMID- 22132459
TI  - Ten years after the 9/11 attacks in the US, post-disaster support groups are
      still much-needed in the UK.

PMID- 22132460
TI  - Step forward.

PMID- 22132461
TI  - Wellbeing through woodwork.

PMID- 22132462
TI  - Speaking up for spirituality.

PMID- 22132463
TI  - Welfare writes. The new test for eligibility for personal independence payment
      could be bad news.

PMID- 22132464
TI  - Outside the box. Section 136 of the Mental Health Act (1983).

PMID- 22132465
TI  - The bigger picture. Overcoming the model of alcoholism.

PMID- 22132466
TI  - A child in mind.

PMID- 22132467
TI  - Women's secure services. Your guide to today's mental health issues.

PMID- 22132468
TI  - Legal eye. The Law Commission's final recommendations for adult social care law.

PMID- 22132469
TI  - Network. NSUN has reached a critical stage.

PMID- 22132470
TI  - Doctor's orders. Undiagnosed bipolar disorder is a major problem.

PMID- 22132471
TI  - Viewpoint. With the NHS reform still on the agenda, mental health doesn't seem to
      be a priority.

PMID- 22132472
TI  - Making the first step to counselling services.

PMID- 22132473
TI  - Health and efficiency.

PMID- 22132474
TI  - On the record. Looking at ordinary people's tales of living with their mental
      illness. Interview by Alita Buttress.

PMID- 22132475
TI  - Challenge and change: lead from the front.

PMID- 22132476
TI  - A retrospective observational study of patient cancellations on the day of
      surgery in the general surgical directorate.
AB  - 'On the day' cancellations carry significant consequences. This article reviews
      all cases that were cancelled on the day of surgery within the general surgical
      directorate of the Royal Hallamshire Hospital, Sheffield from 2005 - 2010. 978
      cancellations were made on the day of surgery. Most significant reasons were due
      to patients' fitness (40%) and lack of theatre time (21%). The conclusion is
      drawn that 80% of cancellations are avoidable or potentially avoidable, and we
      suggest implementation of further strategies to reduce cancellations.

PMID- 22132477
TI  - Cricoid pressure; are we doing it right?
AB  - I am an operating department practitioner (ODP) who routinely applies cricoid
      pressure under the direction of an anaesthetist in order to prevent gastric
      aspiration. This article examines the current use of cricoid pressure in
      anaesthetics.

PMID- 22132478
TI  - 'Hospital-at-Night' expedites review of trauma patients without affecting outcome
      from hip fracture.
AB  - The UK Hospital at Night (H@N) programme is hypothesised to improve efficiency of
      out-of-hours care. No studies have assessed a surgical programme or mechanisms of
      effect. This prospective study aimed to do so in a trauma and orthopaedic
      department over 10 weeks. Senior house officers recorded night shift activity.
      Mean time to attend referrals reduced from 29 to 15 minutes as a result of the
      programme (p = 0.007). Workload and 30 day mortality and morbidity for hip
      fracture remained unchanged. The mechanisms underlying improvements are unclear,
      but may represent central organisation of workload.

PMID- 22132479
TI  - A literature review and guidance for nurse-led patient extubation in the recovery
      room/post anaesthetic care unit: endotracheal tubes.
AB  - A review of current literature highlighted the lack of national or local
      guidelines for post anaesthetic care unit (PACU) practitioners/recovery room
      nurses to extubate their own patients. This article documents the findings of a
      systematic literature review and gives simple diagrammatic representations from a
      comprehensive flow chart that has been developed to assist nurses in the
      extubation process. A knowledge and skills competency validated training package
      was developed locally with the anaesthetic department to train practitioners to
      undertake endotracheal extubation safely.

PMID- 22132480
TI  - To scrub or not to scrub? That is the question.
AB  - The assistant theatre practitioner (ATP) is increasingly being developed across a
      range of healthcare settings to support the role of the registered practitioner
      (Skills for Health 2010). Where ATPs take on roles that were previously the
      domain of registered practitioners, it is essential that safety and quality of
      care is maintained. This article describes the experience within one acute
      hospital trust of implementing an assistant practitioner role in a theatre
      setting and sets out to answer the question--should assistant theatre
      practitioners be allowed to scrub?

PMID- 22132481
TI  - The early days of prostatectomy for benign prostatic hypertrophy.
AB  - The syndrome of bladder neck obstruction, often leading to retention of urine, in
      ageing men has been recognised since earliest times. Catheterisation for the
      relief of urinary retention was used by the ancient Chinese and Egyptians and is
      described in the writings of the Indian surgeon Susrata, who flourished in
      Benares sometime after Christ. Although many of these cases were the result of
      urethral stricture from trauma or gonorrhoea, we can assume that, in older men,
      the cause was often benign prostatic hypertrophy (BPH).

PMID- 22132482
TI  - Doubts cast on health visitor calculations.

PMID- 22132483
TI  - "Healthcare assistants do not need statutory regulation".

PMID- 22132484
TI  - "Admire students who adapt to the specialist club that is A&E".

PMID- 22132485
TI  - "If assisted suicide is legalised, are nurses best placed to do it?".

PMID- 22132486
TI  - Assessing the value of electronic records.
AB  - BACKGROUND: With the introduction of electronic records, some nurses have
      expressed concern about the length of time they spend inputting data on
      computers. AIM: To explore mental health nurses' views about computer use when
      engaging with patients in care planning, and to investigate how electronic
      records contribute to improving service user involvement and care planning in
      mental health services. METHOD: A literature review and a descriptive survey
      based on a questionnaire distributed to 10 wards. RESULTS: Respondents raised
      several concerns about electronic records and patient contact. They called for
      more training specifically on electronic care plans. Concerns were voiced about
      duplication of work, with nurses continuing to use paper then rewriting on a
      computer, leaving less time for patient care. A shortage of computers and a lack
      of space where nurses and patients could meet and develop the electronic care
      plan together were also issues. A stated benefit was that patient information was
      easier to read. CONCLUSION: Ongoing training, availability of interview rooms,
      staff attitudes and evaluation of electronic care plans in terms of patient care,
      interaction between nurses and patients, and partnership working need to be
      addressed.

PMID- 22132487
TI  - Complex febrile seizures in children.

PMID- 22132488
TI  - How to care for patients with chronic fatigue syndrome/ME.

PMID- 22132489
TI  - "Practice nurses should know about diabetes in pregnancy".

PMID- 22132490
TI  - How to manage hypoglycaemia.
AB  - Hypoglycaemia is a common side-effect of insulin therapy and of some oral
      hypoglycaemic tablets that stimulate insulin production. It affects quality of
      life, can prevent people with diabetes from achieving the blood glucose control
      required to reduce their risk of diabetes complications, and can also be fatal.
      This article defines hypoglycaemia, what causes it, how can it be identified and
      treated, and how nurses can support people at risk of this disabling and
      frightening condition.

PMID- 22132491
TI  - Carbohydrate counting in diabetes.
AB  - Carbohydrate counting is an effective tool to aid the management of blood glucose
      control in type 1 diabetes. All those with this condition should be offered the
      opportunity to learn about carbohydrate counting at diagnosis and have access to
      structured education programmes such as Dose Adjustment for Normal Eating
      (DAFNE).

PMID- 22132492
TI  - Obstructive sleep apnoea: its link with diabetes.
AB  - Obstructive sleep apnoea (OSA) is a relatively common condition that affects men
      more than women. There is a strong connection between OSA and type 2 diabetes-
      they have shared risks, including obesity, age and ethnicity. This article
      outlines this link and discusses treatment.

PMID- 22132493
TI  - Preventing cardiac death in diabetes.

PMID- 22132494
TI  - Ideas into reality.

PMID- 22132495
TI  - A guide to the six steps of change.

PMID- 22132496
TI  - Lethal entanglement in baleen whales.
AB  - Understanding the scenarios whereby fishing gear entanglement of large whales
      induces mortality is important for the development of mitigation strategies. Here
      we present a series of 21 cases involving 4 species of baleen whales in the NW
      Atlantic, describing the available sighting history, necropsy observations, and
      subsequent data analyses that enabled the compilation of the manners in which
      entanglement can be lethal. The single acute cause of entanglement mortality
      identified was drowning from entanglement involving multiple body parts, with the
      animal's inability to surface. More protracted causes of death included impaired
      foraging during entanglement, resulting in starvation after many months; systemic
      infection arising from open, unresolved entanglement wounds; and hemorrhage or
      debilitation due to severe gear-related damage to tissues. Serious gear-induced
      injury can include laceration of large vessels, occlusion of the nares, embedding
      of line in growing bone, and massive periosteal proliferation of new bone in an
      attempt to wall off constricting, encircling lines. These data show that baleen
      whale entanglement is not only a major issue for the conservation of some baleen
      whale populations, but is also a major concern for the welfare of each affected
      individual.

PMID- 22132497
TI  - Post-epizootic chronic dolphin morbillivirus infection in Mediterranean striped
      dolphins Stenella coeruleoalba.
AB  - Dolphin morbillivirus (DMV) has caused 2 epizootics with high mortality rates on
      the Spanish Mediterranean coast, in 1990 and 2006-07, mainly affecting striped
      dolphins Stenella coeruleoalba. Following the first epizootic unusual DMV
      infections affecting only the central nervous system of striped dolphins were
      found, with histological features similar to subacute sclerosing panencephalitis
      and old dog encephalitis, the chronic latent localised infections caused by
      defective forms of measles virus and canine distemper virus, respectively.
      Between 2008 and 2010, monitoring by microscopic and immunohistochemical (IHC)
      studies of 118 striped dolphins stranded along Catalonia, the Valencia Region and
      Andalusia showed similar localised DMV nervous system infections in 25.0, 28.6
      and 27.4% of cases, respectively, with no significant differences among regions
      or sex. The body length of DMV-infected dolphins was statistically greater than
      that of non-infected dolphins (196.5 vs. 160.5 cm; p < 0.001). Molecular
      detection of DMV was performed by 2 different RT-PCR techniques amplifying a 429
      bp fragment and a 78 bp fragment both within the phosphoprotein (P) gene. The 429
      bp RT-PCR results contradicted the IHC-DMV results as only 3 of 6 dolphins with
      positive IHC-DMV had positive PCR results. All 6 cases were positive with the 78
      bp RT-PCR. These findings contraindicate the use of the 429 bp RT-PCR protocol
      based on the P gene to detect this specific form of DMV. DMV localised nervous
      infection constitutes the most relevant single cause of stranding and death in
      Mediterranean striped dolphins in the years following a DMV epizootic, and it
      might even overwhelm the effects of the epizootic itself, at least in 2007.

PMID- 22132498
TI  - Major capsid protein gene sequence analysis of the Santee-Cooper ranaviruses DFV,
      GV6, and LMBV.
AB  - The Santee-Cooper ranaviruses doctor fish virus (DFV), guppy virus 6 (GV6), and
      largemouth bass virus (LMBV) are members of the genus Ranavirus within the family
      Iridoviridae. The major capsid protein (MCP) is a main structural protein of
      iridoviruses and supports the differentiation and classification of ranaviruses.
      Presently the complete sequence of the MCP gene is known for most ranaviruses
      with the exception of the Santee-Cooper ranaviruses. In the present study, the
      complete nucleotide sequence of the MCP gene of DFV, GV6, and LMBV was
      determined. DFV and GV6 are identical within the MCP gene sequence. The identity
      compared to the corresponding sequence in LMBV amounts to 99.21%. The MCP gene of
      DFV, GV6, and LMBV exhibits only approximately 78% identity compared to the
      respective gene of other ranaviruses. Based on the sequence data obtained in the
      present study, a Rana MCP polymerase chain reaction (PCR) and subsequent
      restriction fragment length polymorphism (RFLP) analysis were developed to
      identify and differentiate ranaviruses, including DFV, GV6, and LMBV.

PMID- 22132499
TI  - Exophiala angulospora causes systemic inflammation in atlantic cod Gadus morhua.
AB  - Species of Exophiala are opportunistic fungal pathogens that may infect a broad
      range of warm- and cold-blooded animals, including salmonids and Atlantic cod. In
      the present study, we observed abnormal swimming behaviour and skin pigmentation
      and increased mortality in cod kept in an indoor tank. Necropsy revealed foci of
      different sizes with a greyish to brownish colour in internal organs of diseased
      fish. The foci consisted of ramifying darkly pigmented fungal hyphae surrounded
      by distinct layers of inflammatory cells, including macrophage-like cells. In the
      inner layer with many hyphae, the macrophage-like cells were dead. We observed no
      apparent restriction of fungal growth by the inflammatory response. A darkly
      pigmented fungus was repeatedly isolated in pure culture from foci of diseased
      fish and identified as Exophiala angulospora using morphological and molecular
      characters. This species has not been previously reported to cause disease in
      cod, but has been reported as an opportunistic pathogen of both marine and
      freshwater fish. Based on the morphology and sequence analysis presented here, we
      conclude that E. angulospora caused the observed chronic multifocal inflammation
      in internal organs of cod, leading to severe disease and mortality.

PMID- 22132500
TI  - Adhesion dynamics of Flavobacterium columnare to channel catfish Ictalurus
      punctatus and zebrafish Danio rerio after immersion challenge.
AB  - The adhesion dynamics of Flavobacterium columnare to fish tissues were evaluated
      in vivo by immersion challenge followed by bacterial plate count and confirmatory
      observations of gill-adhered bacterial cells using scanning electron microscopy.
      Adhesion of F. columnare genomovar I (ARS-1) and II (BGFS-27) strains to skin and
      gill of channel catfish Ictalurus punctactus and gill of zebrafish Danio rerio
      was compared. At 0.5 h post-challenge, both strains adhered to gill of channel
      catfish at comparable levels (10(6) colony forming units [CFU] g(-1)), but
      significant differences in adhesion were found later in the time course. Channel
      catfish was able to effectively reduce ARS-1 cells on gill, whereas BGFS-27
      persisted in gill beyond the first 24 h post-challenge. No significant difference
      was found between both strains when adhered to skin, but adhered cell numbers
      were lower (10(3) CFU g(-1)) than those found in gill and were not detectable at
      6 h post-challenge. Adhesion of BGFS-27 cells to gill of zebrafish also occurred
      at high numbers (> 10(6) CFU g(-1)), while only < 10(2) CFU g(-1) of ARS-1 cells
      were detected in this fish. The results of the present study show that particular
      strains of F. columnare exhibit different levels of specificity to their fish
      hosts and that adhesion to fish tissues is not sufficient to cause columnaris
      disease.

PMID- 22132501
TI  - Geographical variation in spore morphology, gene sequences, and host specificity
      of Myxobolus arcticus (Myxozoa) infecting salmonid nerve tissues.
AB  - Myxobolus arcticus Pugachev and Khokhlov, 1979 is a freshwater myxosporean
      parasite infecting the nerve tissues of salmonid fishes throughout the Pacific
      region of Far East Asia and North America. The principal fish host is sockeye
      salmon Oncorhynchus nerka in North America and masu salmon O. masou in Japan.
      Actinospores of M. arcticus were isolated from the lumbriculid oligochaetes
      Lumbriculus variegatus and Stylodrilus heringianus in Japan and Canada,
      respectively. Morphological comparisons indicated that Japanese actinospores from
      L. variegatus have significantly shorter caudal projections than Canadian
      isolates from S. heringianus, whereas the corresponding myxospores are
      indistinguishable. Transmission experiments showed that sockeye salmon were
      rarely susceptible to the Japanese actinospores, while masu salmon are highly
      susceptible to this parasite. Sequences of 4560 base pairs of the ribosomal RNA
      (rRNA) gene, including small subunit (SSU) and internal transcribed spacer (ITS)
      regions, from Japanese and Canadian isolates had a high similarity over 99.9%,
      suggesting that they may be conspecific. However, the biological data indicate
      that they are at least distinct strains. M. arcticus may be geographically
      isolated due to the specific homing migration of the anadromous fish hosts and
      has specialized its morphology and host selection for its local environment in
      the ongoing process of differentiation, potentially leading to speciation.

PMID- 22132502
TI  - Parasitisation by Bathycreadium elongatum (Digenea, Opecoelidae) in pyloric caeca
      of Trachyrincus scabrus (Teleostei, Macrouridae).
AB  - A novel process of transmural passive displacement of a digenean parasite was
      studied in the digestive tract of the roughsnout grenadier Trachyrincus scabrus,
      which is found in the northwestern Mediterranean Sea. This mechanism seems to
      facilitate the elimination of a significant portion of intestinal parasites. The
      digenean parasite Bathycreadium elongatum was found in the intestine, mainly
      within pyloric caeca, in 74.4% of T. scabrus, with a mean abundance of 44
      individuals per fish. Nodule-like lesions were also found in the mesentery of
      pyloric caeca of infected T. scabrus. Histological sections of the nodules
      revealed granulomatous inflammatory responses surrounding degraded digeneans.
      Partial nucleotide sequences of the 28S rRNA gene obtained from intracaecal B.
      elongatum and from the core of the nodules of the mesentery of pyloric caeca
      showed 100% mutual identity with an overlap of 971 bp. The greatest abundance of
      both intracaecal B. elongatum and nodules occurred in spring. During summer, and
      especially autumn, the abundance of intracaecal B. elongatum decreased.
      Prevalence and abundance of nodules increased in autumn. In winter intracaecal
      parasite abundance and prevalence began to increase, but decreased again in
      nodules. During spring and summer, parasites pass into the visceral cavity,
      hypothetically owing to the fragility of the wall of pyloric caeca in their
      apical zone, and become degraded through a granulomatous inflammatory response.
      This process seems to have a detrimental effect on the B. elongatum cycle since
      some of parasites are trapped and degrade in the connective tissue in which they
      are unable to complete their life cycle.

PMID- 22132503
TI  - Lack of transmission of Hematodinium sp. in the blue crab Callinectes sapidus
      through cannibalism.
AB  - Hematodinium spp. are parasitic dinoflagellates of marine crustaceans. Outbreaks
      of Hematodinium sp. have impacted commercial landings of the blue crab
      Callinectes sapidus in the coastal bays of Virginia and Maryland (USA), with
      seasonal peaks in prevalence reaching 85%. The life cycle and transmission routes
      of the parasite in blue crabs are poorly understood. Cannibalism and waterborne
      transmission may be routes of transmission, although little conclusive evidence
      has been reported for these modes. We examined cannibalism as a route by a series
      of experiments wherein we repeatedly fed adult and juvenile crabs the tissues of
      crabs infected with Hematodinium. In each experiment, feeding was done 3 times
      over the course of 1 wk. Only 2 of 120 crabs were infected within 7 to 9 d after
      feeding, and these 2 were likely infected prior to the experimental exposures.
      Crabs inoculated with hemolymph from infected donors served as positive controls.
      They developed infections over 11 to 21 d, indicating that the Hematodinium sp.
      used in the cannibalism trials was infectious at the time of inoculation. Because
      amphipods also harbor Hematodinium-like infections, we fed tissues of infected
      crabs to the estuarine amphipod Leptocheirus plumulosus. Hematodinium DNA was
      detected in amphipods shortly after feeding, but not in animals held for longer
      periods, nor was it observed in histological preparations. Amphipods did not
      obtain infections by scavenging infected crab tissues. Our results show that
      Hematodinium sp. is not effectively transmitted through ingestion of diseased
      tissues, indicating that cannibalism may not be a major route of transmission for
      Hematodinium sp. in blue crabs.

PMID- 22132504
TI  - Multicentric infiltrative lipoma in a farmed Mediterranean seabass Dicentrarchus
      labrax: a pathological and biochemical case study.
AB  - A tumour diagnosed as multicentric infiltrative lipoma affecting a single farmed
      seabass is described. The fish had 3 masses on the lateral side of its back,
      deforming the skin surface. The masses showed a tendency to invade the underlying
      musculature. Histologically, the neoplasm consisted of differentiated adipocytes.
      Biochemically, the neoplastic tissue showed lower values of monounsaturated fatty
      acids and higher values of polyunsaturated fatty acids compared with adjacent
      normal muscular tissue, particularly of the n3 series, such as eicosapentanoic
      (C20:5n3) and docosahexanoic (C22:6n3) acids. Data obtained suggest a metabolic
      disturbance in the lipid component of the muscular tissue metabolic pathway,
      which could be the starting point to promote lipoma formation. This is the first
      report of lipoma in Mediterranean seabass.

PMID- 22132505
TI  - Static and dynamic visual information about the size and passability of an
      aperture.
AB  - The role of static eyeheight-scaled information in perceiving the passability of
      and guiding locomotion through apertures is well established. However, eyeheight
      scaled information is not the only source of visual information about size and
      passability. In this study we tested the sufficiency of two other sources of
      information, both of which are available only to moving observers (ie are
      dynamic) and specify aperture size in intrinsic body-scaled units. The experiment
      was conducted in an immersive virtual environment that was monocularly viewed
      through a head-mounted display. Subjects walked through narrow openings between
      obstacles, rotating their shoulders as necessary, while head and shoulder
      position were tracked. The task was performed in three virtual environments that
      differed in terms of the availability of eyeheight-scaled information and the two
      dynamic sources of information. Analyses focused on the timing and amplitude of
      shoulder rotation as subjects walked through apertures, as well as walking speed
      and the number of collisions. Subjects successfully timed and appropriately
      scaled the amplitude of shoulder rotation to fit through apertures in all three
      conditions. These findings suggest that visual information other than eyeheight
      scaled information can be used to guide locomotion through apertures.

PMID- 22132506
TI  - Transient attention degrades perceived apparent motion.
AB  - Transient spatial attention refers to the automatic selection of a location that
      is driven by the stimulus rather than a voluntary decision. Apparent motion is an
      illusory motion created by stationary stimuli that are presented successively at
      different locations. In this study we explored the effects of transient attention
      on apparent motion. The motion target presentation was preceded by either valid
      attentional cues that attract attention to the target location in advance
      (experiments 1-4), neutral cues that do not indicate a location (experiments 1,
      3, and 4), or invalid cues that direct attention to a non-target location
      (experiment 2). Valid attentional cues usually improve performance in various
      tasks. Here, however, an attentional impairment was found. Observers' ability to
      discriminate the direction of motion diminished at the cued location. Analogous
      results were obtained regardless of cue type: singleton cue (experiment 1),
      central non-informative cue (experiment 2), or abrupt onset cue (experiment 3).
      Experiment 4 further demonstrated that reversed apparent motion is less likely
      with attention. This seemingly counterintuitive attentional degradation of
      perceived apparent motion is consistent with several recent findings, and
      together they suggest that transient attention facilitates spatial segregation
      and temporal integration but impairs spatial integration and temporal
      segregation.

PMID- 22132507
TI  - Visual chimaeras obtained with the Riesz transform.
AB  - Similar to an auditory chimaera (Smith et al, 2002 Nature 416 87-90), a visual
      chimaera can be defined as a synthetic image which has the fine spatial structure
      of one natural image and the envelope of another image in each spatial frequency
      band. Visual chimaeras constructed in this way could be useful to vision
      scientists interested in the study of interactions between first-order and second
      order visual processing. Although it is almost trivial to generate 1-D chimaeras
      by means of the Hilbert transform and the analytic signal, problems arise in
      multidimensional signals like images given that the partial directional Hilbert
      transform and current 2-D demodulation algorithms are anisotropic or orientation
      variant procedures. Here, we present a computational procedure to synthesise
      visual chimaeras by means of the Riesz transform--an isotropic generalisation of
      the Hilbert transform for multidimensional signals--and the associated monogenic
      signal--the vector-valued function counterpart of the analytic signal in which
      the Riesz transform replaces the Hilbert transform. Examples of visual chimaeras
      are shown for same/different category images.

PMID- 22132508
TI  - Cast shadows in wide perspective.
AB  - We investigated the apparent spatial layout of cast shadows up to very wide
      fields of view. We presented up to 130 degrees wide images in which two 'flat
      poles' were standing on a green lawn under a cloudless blue sky on a sunny day.
      The poles threw sharp cast shadows on the green, of which one was fixed. The
      observer's task was to adjust the azimuth of the shadow of the other pole such
      that it fitted the scene. The source elevation was kept constant. The two cast
      shadows are, of course, parallel in physical space, but generically not in the
      picture plane because of the wide perspective. We found that observers made huge
      systematic errors, indicating that, generically, they fail to account for these
      perspective effects. The systematic deviations could be well described by a
      weighted linear combination of the directions in the picture plane and in the
      physical space, with weights that depended on the positions of, and distance
      between, the poles.

PMID- 22132509
TI  - Judging political affiliation from faces of UK MPs.
AB  - Subjects were shown photographs of UK MPs' faces and asked to judge their
      political affiliations. Participants were unable to correctly distinguish between
      Conservative and Labour politicians. However, their responses were used to create
      computer-generated idealised faces representative of each party, which
      independent evaluators could correctly identify. These faces give an indication
      of the mental images we might reference when imagining MPs from the two main UK
      political parties.

PMID- 22132510
TI  - Perceived size and perceived direction: the interplay of the two descriptors of
      visual space.
AB  - The stimulus in the outdoor psychophysical experiment was formed by two rods
      placed on the ground plane over a range of possible distances and orientations.
      Observers estimated its size and direction by positioning the third rod in the
      neighbouring space to form an evenly spaced collinear triple of rods. The data
      revealed interesting similarities between the profiles of the deviations in both
      judgments: for size judgments, the variability of the responses was least when
      the targets were at a frontal orientation and gradually increased as the
      orientation approached the medial plane. For direction judgments, on the other
      hand, the variability of the responses was least when the stimuli were aligned
      with the observer's line of sight and gradually increased as the orientation
      approached the frontoparallel plane. The finding of inverse relationship between
      the precision of size and direction judgments is interpreted as a consequence of
      the unequal precision in localisation between the frontal and in-depth dimensions
      of visual space. The question of the best parameterisation of the observers'
      responses is discussed.

PMID- 22132511
TI  - Judgments of reachability are independent of visuomotor adaptation.
AB  - The furthest distance that is judged to be reachable can change after
      participants have used a tool or if they are led to misjudge the position of
      their hand. Here we investigated how judged reachability changed when visual
      feedback about the hand was shifted. We hoped to distinguish between various ways
      in which visuomotor adaptation could influence judged reachability. Participants
      had to judge whether they could reach a virtual cube without actually doing so.
      They indicated whether they could reach this virtual cube by moving their hand.
      During these hand movements, visual feedback about the position of the hand was
      shifted in depth, either away from or toward the participant. Participants always
      adapted to the shifted feedback. In a session in which the hand movements in the
      presence of visual feedback were mainly in depth, perceived reachability shifted
      in accordance with the feedback (more distant cubes were judged to be reachable
      when feedback was shifted further away). In a second session in which the hand
      movements in the presence of visual feedback were mainly sideways, for some
      participants perceived reachability shifted in the opposite direction than we
      expected. The shift in perceived reachability was not correlated with the
      adaptation to the shift in visual feedback. We conclude that reachability
      judgments are not directly related to visuomotor adaptation.

PMID- 22132512
TI  - Binocular disparity magnitude affects perceived depth magnitude despite inversion
      of depth order.
AB  - The hollow-face illusion involves a misperception of depth order: our perception
      follows our top-down knowledge that faces are convex, even though bottom-up depth
      information reflects the actual concave surface structure. While pictorial cues
      can be ambiguous, stereopsis should unambiguously indicate the actual depth
      order. We used computer-generated stereo images to investigate how, if at all,
      the sign and magnitude of binocular disparities affect the perceived depth of the
      illusory convex face. In experiment 1 participants adjusted the disparity of a
      convex comparison face until it matched a reference face. The reference face was
      either convex or hollow and had binocular disparities consistent with an average
      face or had disparities exaggerated, consistent with a face stretched in depth.
      We observed that apparent depth increased with disparity magnitude, even when the
      hollow faces were seen as convex (ie when perceived depth order was inconsistent
      with disparity sign). As expected, concave faces appeared flatter than convex
      faces, suggesting that disparity sign also affects perceived depth. In experiment
      2, participants were presented with pairs of real and illusory convex faces. In
      each case, their task was to judge which of the two stimuli appeared to have the
      greater depth. Hollow faces with exaggerated disparities were again perceived as
      deeper.

PMID- 22132513
TI  - Discrepant integration times for upright and inverted faces.
AB  - Judgments of upright faces tend to be more rapid than judgments of inverted
      faces. This is consistent with encoding at different rates via discrepant
      mechanisms, or via a common mechanism that is more sensitive to upright input.
      However, to the best of our knowledge no previous study of facial coding speed
      has tried to equate sensitivity across the characteristics under investigation
      (eg emotional expression, facial gender, or facial orientation). Consequently we
      cannot tell whether different decision speeds result from mechanisms that accrue
      information at different rates, or because facial images can differ in the amount
      of information they make available. To address this, we examined temporal
      integration times, the times across which information is accrued toward a
      perceptual decision. We examined facial gender and emotional expressions. We
      first identified image pairs that could be differentiated on 80% of trials with
      protracted presentations (1 s). We then presented these images at a range of
      brief durations to determine how rapidly performance plateaued, which is
      indicative of integration time. For upright faces gender was associated with a
      protracted integration relative to expression judgments. This difference was
      eliminated by inversion, with both gender and expression judgments associated
      with a common, rapid, integration time. Overall, our data suggest that upright
      facial gender and expression are encoded via distinct processes and that
      inversion does not just result in impaired sensitivity. Rather, inversion caused
      gender judgments, which had been associated with a protracted integration, to
      become associated with a more rapid process.

PMID- 22132514
TI  - Long-term adaptation effects of highly familiar faces are modulated by adaptation
      duration.
AB  - Adaptation to manipulated versions of face images can induce strong adaptation
      effects in face perception and the adjustment of memory representations has been
      suggested to underlie this effect. In previous studies such effects have been
      observed after short as well as long delays between adaptation and test (5 min
      and 24 h) and they were evident in face images identical to the adapting stimuli
      as well as in new images of the same individual and in faces that were not shown
      during adaptation (factor transferability). By using regression analysis, here we
      show that adaptation duration modulates the size of the adaptation effect, which
      was evident after both short and long time delays and across all levels of
      transferability tested.

PMID- 22132515
TI  - Arcs in perceptual space--going off at a tangent.
AB  - Underestimating the curvature of an arc may result from our tendency to view it
      as prolonged in the direction of the tangent to its ends. Support is given here
      for this hypothesis, but evidence is also provided that tangent deviation may
      alter an arc's circularity along its whole length.

PMID- 22132516
TI  - Simultaneous perception of both interpretations of ambiguous figures.
AB  - When viewing ambiguous figures like the classic duck/rabbit, people alternately
      perceive one interpretation and then the other, but not both interpretations at
      once. When two identical ambiguous figures appear together, the majority of
      observers perceive them as identical, and they typically alternate in unison.
      Just as most observers cannot see a single figure as both a duck and a rabbit,
      most cannot see one figure in a pair as a duck and the other as a rabbit even
      though the two figures and their features are spatially distinct. Is this
      inability to see both interpretations an inherent limitation of the visual system
      or is it just due to differences in top-down processing? We show that a simple
      prompt immediately allows people to see both interpretations, to their own
      surprise.

PMID- 22132517
TI  - Opponent colours induced by rotating discs.
AB  - We found a novel visual illusion by using a rotating disc that has some coloured
      sectors with black arcs. When this disc rotates, illusory colours are seen in the
      concentric rings that are created by the rotating arcs. The illusory colours are
      the opponent colours of the sectors that the corresponding arcs are in. Even
      though we could not differentiate the colours of the individual sectors when the
      disc rotated quickly, the illusory colours that were the opponent colours of the
      sector colours could be seen. This visual illusion thus suggests that our visual
      system can process visual stimuli that we cannot perceive as colours.

PMID- 22132518
TI  - Safeguard nurses at war.

PMID- 22132519
TI  - Just because I'm old!

PMID- 22132520
TI  - Professional conduct.

PMID- 22132521
TI  - Credentialling--what's in it for me?

PMID- 22132522
TI  - Campaign to wind back the Fair Work Act.

PMID- 22132523
TI  - Respecting patient choices.

PMID- 22132524
TI  - Supervision: a great addition to the wellbeing toolkit.

PMID- 22132525
TI  - Strength in unity: ANF biennial national delegates conference.

PMID- 22132526
TI  - An evidence-based guideline for polycystic ovary syndrome.

PMID- 22132527
TI  - Gaining the trust of youth.

PMID- 22132528
TI  - Mental health care for exploring detainees: a fundamental recovery human right.

PMID- 22132529
TI  - Consumer participation: power and change.

PMID- 22132530
TI  - Simulation in mental health education.

PMID- 22132531
TI  - Accommodation needs and mental illness.

PMID- 22132533
TI  - Bula to our comrades in Fiji.

PMID- 22132532
TI  - Rethinking leadership in mental health nursing.

PMID- 22132534
TI  - Midwives and women together.

PMID- 22132535
TI  - Eating your words: getting the right messages across.
AB  - Routine visits to primary care settings give health professionals a valuable
      opportunity to discuss sexual health with women, but may also be a first step in
      discussing a pregnancy; planned or otherwise. Since nutrition plays a vital role
      in any healthy pregnancy, it's a golden opportunity to give advice about good
      nutrition--both for the expectant mum and for her growing family--to ensure a
      safe and healthy pregnancy. Dr Frankie Phillips here provides plenty of
      information about what constitutes a healthy diet during pre-conception and
      pregnancy. This article discusses the key components of advice regarding
      nutrition and food safety for pregnant women in the UK.

PMID- 22132536
TI  - Breastfeeding Solution Circle.
AB  - It is widely accepted and backed by research that breastfeeding is the number one
      feeding choice for babies, and direct from mothers' breasts is the ideal. However
      the early days can be challenging. Supporting mothers to succeed with their
      breastfeeding journey is a rewarding role and being able to advise and guide on
      overcoming the various hurdles is great. Keeping up to date on the research and
      advancements in breastfeeding support is vital and a general knowledge of the
      solutions to help will be of huge benefit to the mothers you are working with.
      This article examines the problems and some tried and tested solutions.

PMID- 22132537
TI  - Apple dumplings: the story of a breastfeeding video.
AB  - Just before last Christmas (2010) I had an idea to make a breastfeeding
      promotional video. Of course my ideas and visions were ones of grandeur where
      with a letter or two to the appropriate Government departments, I would have
      financing and backing for the project. Recognition in regards to the importance
      of such a message would be given and the road to making my video would be smooth.
      Little did I know the fight ahead I would have in trying to raise some money, to
      get publicity for what I was doing or to get "important folk" involved. However I
      do have a certain amount of determination and more importantly really believed in
      what I wanted to do, so I counted on the help I could get, which was from
      dedicated past and present breastfeeding mothers themselves and good old Facebook
      to spread the word. I changed track a little and decided to make the video a bit
      of fun with a message. A bit like comic relief, a serious subject lightheartedly
      presented with the aim being to help make a difference. I wanted the video to be
      a bit different from the factual educational ones that are already around and I
      wanted it to get attention. What better way than to use a little bit of humour, a
      bit of tongue in cheek glamour and the mums themselves to play starring roles.
      So, slowly the theme for the video began to take shape, ideas came together and
      the Apple Dumplings project was to take up the next eight months of my life, a
      huge amount of my own savings; and it continues to do so as I write this
      reflection.

PMID- 22132538
TI  - At home in early labour: what fathers do and how they feel--part 1.
AB  - A survey of fathers from across the UK was carried out to explore their
      experience of being at home with their partners in early labour. Respondents were
      recruited via the Fatherhood Institute website and by contacting children's
      centres. Two hundred and sixty three men from diverse backgrounds responded.
      Approximately two fifths had found that early labour matched up to their
      expectations, but many fathers had been greatly or somewhat surprised by what
      happened. In terms of deciding when to leave home and go to the hospital or birth
      centre, fathers did not generally see themselves as the primary decision makers,
      but half had been either primarily or jointly responsible for the decision. There
      is therefore a strong case for ensuring that expectant fathers are given
      information when attending clinics or antenatal classes with their partners to
      help them understand the latent phase of labour and signs of established labour.

PMID- 22132539
TI  - Scratching can reveal more than just an itch.
AB  - The simplest definition of obstetric cholestasis (OC) is 'sluggish or interrupted
      bile flow in pregnancy'. In affected women the normal flow of bile out of the
      liver is reduced and this leads to raised bile salts (also referred to as bile
      acids) in the blood. This, together with abnormal liver function tests and the
      symptom of itch, may result in a woman being diagnosed with the condition of OC.
      Yet OC cannot be classified as one single disease. It is more accurate to think
      of it as a clinical state where a pregnant woman presents with a specific
      collection of symptoms and blood results together. This can occur in the context
      of several disorders, such as hepatitis C infection, adverse drug reaction or
      acute fatty liver of pregnancy, or can occur as a diagnosis that is only caused
      by pregnancy. Regardless of the underlying cause, OC is a condition that has the
      potential threat of stillbirth and myriad variables all of which make it
      challenging for clinicians to know how to treat and manage it. In this article
      Jenny and Alice show what these variables are and why there may be a risk of
      stillbirth.

PMID- 22132540
TI  - Use of technology in childbirth: 1. The role of the midwife past, present and
      future.

PMID- 22132541
TI  - Henderson L, McMillan B, Green JM et al (2011). Birth, 38(1): 61-70. Men and
      infant feeding: perceptions of embarrassment, sexuality and social conduct in
      white low-income British men.

PMID- 22132542
TI  - Breastfeeding and the neonatal ward.
AB  - The evidence base showing the huge importance of breast milk for preterm babies
      is growing all the time. Human milk can help save the lives of vulnerable babies
      as well as help prevent some of the long-term complications. Breast milk is being
      seen as one of the most potent medicines for these babies. Yet practice in many
      neonatal wards is lagging behind the evidence. In this article, Sarah Vincent
      interviews Dr Paul Meier, one of the high profile speakers coming to the 2011
      UNICEF UK Baby Friendly Conference later this year, who has carried out
      pioneering work into caring for preterm babies at the Neonatal Intensive Care
      Unit at Rush University Medical Center in Chicago. In her unit, where
      breastfeeding initiation rates are now 98 per cent, much of the care is carried
      out by well trained peer supporters who have been through the experience
      themselves and whom mothers can easily relate to. Dr Meier has also carried out
      research into the importance of the first two weeks for establishing a milk
      supply for mothers using a milk pump.

PMID- 22132543
TI  - Let's support each other to support women.

PMID- 22132544
TI  - Meeting our challenges head on.

PMID- 22132545
TI  - Volunteering as a paravocation.

PMID- 22132546
TI  - A demographic study of intraoral malignancies in Minnesota from 1993-2008.

PMID- 22132547
TI  - Endodontic diagnostic terminology update.
AB  - Determination of the etiology of the patient's chief complaint and a correct
      diagnosis are paramount prior to a recommendation of endodontic therapy.
      Reproduction of the patient's chief complaint is critical. If the chief complaint
      cannot be reproduced, consider consultation with or referral to an endodontist or
      orofacial pain specialist. The diagnostic terminology presented in this update
      provides for a more accurate description and communication of the health or
      pathological conditions of both pulpal and apical tissues. This information is
      summarized in Table I.

PMID- 22132548
TI  - On paper.

PMID- 22132549
TI  - Diagnostic radiology meets nuclear terrorism.

PMID- 22132550
TI  - Happiness in dentistry.

PMID- 22132551
TI  - What's a dentist to do? The season of pride.

PMID- 22132552
TI  - Don't be afraid to speak up.

PMID- 22132553
TI  - Neonatal circumcision: healthy practice or barbaric procedure?

PMID- 22132554
TI  - Promoting effective interventions for sleep problems.
AB  - Health visitors and children's nurses can do much to help families prevent the
      development of sleep problems in children with and without disabilities, and to
      treat existing disorder. Sleep difficulties among children with learning
      disabilities are common and receive inadequate attention in most practitioners'
      training. This needs to be urgently addressed because untreated issues may
      persist into adulthood. A sound knowledge of sleep theory, the increasing
      literature on sleep, and the high quality sleep practitioner training that is
      available can all support health professionals in this role. Working in
      partnership with the family and carers is fundamental to success. Specialist
      services such as children's learning disability nursing teams, child and
      adolescent mental health services and sleep centres can assist with complex
      cases.

PMID- 22132555
TI  - Whistleblowing: a legal commentary.
AB  - This article examines the legal position of a nurse who believes that a colleague
      is performing below the level of competence required, witnesses inappropriate
      action by a colleague, or who believes that the care environment is putting
      patients at risk.

PMID- 22132556
TI  - What's wrong with me? Coming to terms with same sex attraction.
AB  - Many, if not all, young people question what is wrong with them when they begin
      to realise that they are attracted to people of the same sex. This can be because
      of feelings of confusion, guilt and shame, which can develop in reaction to the
      society in which they live; feelings that are often mirrored by the families of
      the young people concerned. This article explains the theories behind sexuality
      to help nurses provide unprejudiced, appropriate support and information to
      children and young people seeking help.

PMID- 22132557
TI  - Psychological support for nurses on paediatric intensive care units.
AB  - Nurses on paediatric intensive care units (PICUs) are particularly vulnerable to
      emotional exhaustion and burnout due to critical incidents in the workplace. This
      article examines whether the level of psychological support offered to PICU
      nurses is adequate.

PMID- 22132558
TI  - Opioid-induced constipation in children's palliative care.
AB  - Accurate assessment and management of children's symptoms at the end of life is a
      vital part of the children's nurse role. Most children experience pain at this
      stage and opioids are the drug of choice in those requiring a palliative approach
      to care. Opioids are, however, not without side effects; the most common is
      constipation. This can cause additional stress and anxiety for children and their
      parents at what is already a difficult time. A number of assessment tools are
      available to assist nurses and other members of the care team to work with
      children and parents in identifying risk factors for constipation and its
      severity. Conventional management of opioid-induced constipation consists of
      stool softening or peristalsis stimulating laxatives, and often this is
      effective; however, laxatives also have side effects which can be distressing.
      This article looks at novel approaches to managing opioid-induced constipation
      that are beginning to come to the fore, although there is limited reference to
      their use in children's palliative care.

PMID- 22132559
TI  - Anarchy in the UK: why nutrition deserves to take centre stage.

PMID- 22132560
TI  - First tastes.

PMID- 22132561
TI  - All talk: the importance of early conversations with children.
AB  - Early and relevant conversations can aid childhood development. Numerous
      innovative studies have highlighted the importance of early interaction,
      including the SUMS project and Mental State Talk (MST), which can aid the child's
      development of social understanding and non-literal aspects of communication,
      such as joking and sarcasm.

PMID- 22132563
TI  - Brush up on your technique: good habits start young.

PMID- 22132562
TI  - A topic in 10 questions: how to manage infant constipation.

PMID- 22132564
TI  - Go with the flow: in childhood constipation.
AB  - Childhood constipation is generally idiopathic and has a prevalence of five to 30
      per cent. It can have significant implications on the quality of life for both
      the child and their family. Families may delay presentation as they may feel
      embarrassed or fear receiving a negative response from the healthcare
      professionals. Parents may report different symptoms as "constipation" depending
      on their own beliefs and previous experiences. A detailed history taken with the
      parents, along with a review of the Bristol Stool Form Scale chart will help in
      establishing a clinical diagnosis of constipation in the child. Suspicion of any
      "red flag" symptoms, such as delay in passage of meconium for greater than 48
      hours after birth, toothpaste-like stool, etc, should initiate early referral to
      the paediatric services. Dietary intervention alone is not sufficient in treating
      constipation. Laxative therapy alongside dietary and lifestyle modifications will
      help manage constipation in the community. Health visitors in contact with the
      families concerned can help in early intervention, which is known to produce
      better outcomes.

PMID- 22132565
TI  - Dyspraxia series: Part Two. One step forward.
AB  - Dyspraxia is an often under-diagnosed problem that describes a difficulty in
      managing certain motor tasks. It's an impairment of the organisation of movement
      and also an immaturity in the way the brain processes information. This
      immaturity results in messages not being properly or fully transmitted. In brief,
      dyspraxia affects the planning of what to do and how to do it and is associated
      with problems of perception, language and thought. There are a variety of causes
      and therapy based on the knowledge of these allow affected individuals to reach
      their full developmental potential.

PMID- 22132566
TI  - Every child deserves a school nurse.

PMID- 22132567
TI  - Oral health care for hospitalized children.
AB  - Oral health care may be the greatest unmet health need of children in the U.S.
      Half of the children in the U.S. suffer from tooth decay by 8 years of age. The
      consequences of poor oral health are many, including mouth pain, inability to
      chew and eat, abscess and soft tissue infection, diminished self-esteem, and
      impaired school performance. Numerous medical conditions, such as asthma and
      diabetes, and developmental disabilities, such as cerebral palsy and autism, have
      associated oral health implications. Oral health care is often neglected by
      nondental health providers. Nurses are in a unique position to contribute to the
      improvement of this national health problem by promoting oral health care among
      hospitalized children and their families. A hospital program for oral health care
      is proposed, including assessment of teeth and gingiva, ensuring oral care for
      all, as well as oral health education as part of patient education.

PMID- 22132568
TI  - Improving parent satisfaction by sharing the inpatient daily plan of care: an
      evidence review with implications for practice and research.
AB  - The hospitalization of a child is a stressful time for a parent. The uncertainty
      of diagnosis or prognosis, being away from work and/or home, and possible
      financial concerns are factors that cause stress. One factor that should not be
      cause for stress is poor communication with the health care team. Timely and
      consistent information from patient rounds can minimize this stress factor. This
      article presents a review and critical appraisal of the evidence found to
      identify the best practice for communicating to parents who are not present
      during inpatient rounds. The literature review did not find direct evidence about
      the use of a structured method versus an unstructured method to share information
      with parents. However, this article describes the evidence that exists regarding
      what family members desire during the hospitalization of their child. The review
      of evidence reveals relationships exist between rounds, communication, and
      parent/family satisfaction with the hospital stay.

PMID- 22132569
TI  - Perceptions of school nurses and teachers of fatigue in children.
AB  - The aim of this study was to elicit school nurses' and teachers' perceptions of
      fatigue in school settings. Fatigue was defined as tiredness, not relieved by
      usual sleep or rest; a symptom that persists beyond an isolated experience of
      feeling tired. Four focus groups were conducted to elicit data for this
      qualitative descriptive study. Purposive sampling was used to identify school
      nurse and teacher participants who were asked to discuss their perceptions of
      fatigue. Content analysis of verbatim transcripts yielded several major themes.
      Forty-six codes emerged from the data and were routinely applied during the
      analysis. Nineteen of these codes were used 20 times or more and applied to all
      four transcripts. Participants could clearly identify and readily discuss
      behaviors related to fatigue. Data describe how children attending school express
      fatigue in their everyday life. Findings validate the need for nurses in
      ambulatory pediatric settings to be aware of fatigue as a symptom that children
      and adolescents may experience.

PMID- 22132570
TI  - Focus groups.
AB  - McCabe (2011) was able to validate her hunch that teachers and nurses observed
      symptoms of fatigue in school-aged children. She provides specific examples of
      their comments to illustrate themes and patterns she found in focus group data.
      These examples support and provide the rationale for her conclusions. Qualitative
      research reports commonly contain such examples rather than tables and
      statistical analyses. Before interpreting the findings of qualitative research,
      the investigator compares the study findings to previous research, looking for
      additional support or contrary findings. Dr. McCabe also suggests ways to build
      on this study and recommends future topics for investigation. Focus groups may
      seem particularly well suited to many topics in nursing because they often
      involve families and community groups. This qualitative methodology is an
      excellent way to get a "bird's eye view" of the opinions, values, and feelings
      about research problems, particularly in the initial and early stages. The reader
      may want to review other articles describing studies using focus group methods in
      the "Additional Readings" section below.

PMID- 22132571
TI  - The growing burden of obesity in Thailand: a review of current trends and
      policies.
AB  - In recent years, there has been a rise in obesity-related diseases in
      transitional countries. These countries, once plagued with problems related to
      infectious disease and poverty, now face a dual burden of both chronic and
      infectious diseases. Thailand has recently experienced significant economic
      growth, and as a result, the numbers related to obesity and obesity-related
      diseases have risen significantly. Thailand is an important region to examine the
      timely issue of obesity-related policy because Thailand has been a model for
      successful public health interventions and policies throughout Asia. Further,
      such policies have significant implications for other regions of the world
      experiencing similar health transitions.

PMID- 22132572
TI  - Topical vs. systemic treatments for acute otitis media.
AB  - Acute otitis media (AOM) is a common condition in children that is often treated
      with systemic antibiotic therapy; however, research suggests that non-complicated
      AOM will resolve spontaneously using only eardrops. To determine best practice
      for the use of systematic antibiotics compared to topical treatment of AOM, a
      systematic review of evidence was conducted. Cochrane, Medline, CINAHL, and other
      databases were searched. Inclusion criteria were studies published from 1995-2010
      that included children with AOM and were randomized controlled trials (RCTs).
      Five systematic reviews and five RCTs were included in the review. Current
      evidence recommends using topical and other alternative approaches for treating
      non-complicated AOM in children 2 years of age or older; however, many
      practitioners are not currently following these recommendations for various
      reasons. Additional research to address these reasons may help determine how to
      improve practitioner adherence to best practice evidence and guidelines to help
      reduce the unnecessary use of systemic antibiotics.

PMID- 22132574
TI  - The stories behind the stats: NACHRI quality transformation network reaches
      milestone.

PMID- 22132573
TI  - Pediatric palliative care: starting a hospital-based program.
AB  - The value of palliative care in pediatrics has received significant attention
      over the past 10 years. The American Academy of Pediatrics and the Institute of
      Medicine published recommendations involving children who have a life-limiting
      diagnosis in a palliative care program early in their disease process. Palliative
      care is intended to assure an emphasis on quality of life in addition to the
      current medical treatment, which may be focused on cure, symptom management,
      and/or end-of-life care. This article describes one hospital's experience in
      planning, implementing, and managing a pediatric palliative care program.
      Implementing a hospital-based palliative care program in a children's hospital
      can be accomplished through careful planning and analysis of need. Writing an
      official business plan formalized the request for organizational support for this
      program, including the mission and vision, plans for how services would be
      provided, expected financial implications, and initial plans for evaluation of
      success.

PMID- 22132575
TI  - Adolescent sexual health and physical disability in primary care.

PMID- 22132576
TI  - Catch-22.

PMID- 22132577
TI  - Dental lab industry in decline.

PMID- 22132579
TI  - Practical morality.

PMID- 22132578
TI  - Dental lab industry in decline.

PMID- 22132580
TI  - No reported errors as UCSF phases in new robotic pharmacy.

PMID- 22132581
TI  - Translating the caries management paradigm into practice: challenges and
      opportunities.
AB  - In an era of evidence-based care, the question of how much evidence is needed to
      implement changes into practice becomes central to dentistry's recognition that
      dental caries management must change to a focus on risk-based, patient-centered
      disease management rather than just restorative care. This article reviews some
      of the opportunities, needs, and challenges involved in the adoption and
      implementation of caries management strategies into everyday clinical practice.

PMID- 22132582
TI  - Validation of the CDA CAMBRA caries risk assessment--a six-year retrospective
      study.
AB  - The present manuscript presents the results of a six-year retrospective study
      validating caries risk assessment in a caries management by risk assessment
      program in a large predominantly adult patient population seeking dental care.
      CRA was successful in accurately identifying patients at high caries risk. Caries
      risk assessment in a CAMBRA program is a good clinical tool for everyday dental
      practice.

PMID- 22132583
TI  - New directions in the etiology of dental caries disease.
AB  - This review explores the multifactorial etiology of dental caries disease.
      Current theories suggest that a singular focus on mutans streptococci and
      lactobacillus as the sole causative microbiological agents is no longer a viable
      strategy in treatment of this prevalent disease. Dental caries is an infectious
      transmissible disease process where a cariogenic biofilm in the presence of an
      oral status that is more pathological than protective leads to the
      demineralization of dental hard tissue.

PMID- 22132584
TI  - Into the future: keeping healthy teeth caries free: pediatric CAMBRA protocols.
AB  - Early childhood caries prevalence has increased significantly in children ages 2
      5 years. ECC disproportionately affects lower socioeconomic and minority groups,
      is a predictor for future decay, but is preventable and manageable. Caries risk
      assessment systematically derives a patient's caries risk and is important during
      an infant oral health visit beginning at age 1. Information obtained through a
      risk assessment can guide a disease management care path tailored to an
      individual's age and risk to effectively treat and manage one's caries disease
      process.

PMID- 22132585
TI  - Prevention-centered caries management strategies during critical periods in early
      childhood.
AB  - The current caries management model in the United States is based on restoring
      teeth rather than preventing disease. Scarce resources make this approach
      unsustainable, especially in clinical settings that serve vulnerable child
      populations. This paper presents specific prevention-centered caries management
      strategies that should form the basis of clinical interventions targeted at
      children during four critical periods in childhood: pre-age 1, ages 1-3, ages 4
      5, and ages 6-7.

PMID- 22132586
TI  - Motivational interviewing concepts and the relationship to risk management and
      patient counseling.
AB  - A brief version of motivational interviewing, a patient-centered counseling
      technique, has been found to be effective in reducing caries in high-risk young
      children. Motivational interviewing principles are discussed, examples of
      motivational interviewing interactions are provided, and the concept of readiness
      is presented in this paper. Dental professionals using caries management by risk
      assessment can readily use motivational interviewing strategies to reduce risks.

PMID- 22132587
TI  - Changing the face and practice of dentistry: a 10-year plan.
AB  - Jan. 7 through 9, 2011, the California Dental Association Foundation hosted a
      symposium on caries management by risk assessment in which a diverse range of
      stakeholders from across the nation gathered to discuss current and future status
      of CAMBRA. The consensus of the group was to develop a national strategic plan
      for CAMBRA implementation which will chart the course to improve the standard in
      caries disease management within the next decade. This paper represents the
      initial start of this living document.

PMID- 22132588
TI  - The information age.

PMID- 22132589
TI  - Guidelines and avoiding meltdown.

PMID- 22132590
TI  - Learning through incident reporting: time to consider a national incident
      reporting system.

PMID- 22132591
TI  - Point-of-care ultrasonography.

PMID- 22132592
TI  - Patterns of scald injuries in children--has anything changed?
AB  - The objective was to study presentation patterns of scald injuries in children
      and suggest potential countermeasures to reduce these injuries. We
      retrospectively studied scald injuries in children attending an urban paediatric
      emergency department between January 1st and December 31st 2008. Data was
      extracted from our emergency department database using search terms 'burn',
      'scald', 'other burn'. Scalds were analysed for; age at presentation, sex, time
      of presentation, causal agent, scald outcome and treatment required. Burns
      accounted for 280 (0.66%) of total attendees, 161 (57%) were scalds. 127 (79%)
      were under 5 years old (mean age 42 months). 104 (65%) were caused by hot
      beverages, 25 (16%) hot water and 16 (10%) hot food stuffs. 97 (60%) presented
      within 1 hour of injury. 40 (25%) received first aid. The most affected areas
      were upper limbs 79 (35%) and upper trunk 74 (33%). Overall 45 (28%) were
      discharged home requiring no further treatment, 9 (6%) were admitted to hospital
      and 101 (63%) attended dressing clinic or plastic surgery OPD. Our results are
      consistent with other studies and illustrate that the incidence and pattern of
      scald injuries have not changed over the past decade. Scalds will continue to be
      a significant cause of unintentional injury and morbidity among young children
      unless preventative strategies are devised and employed.

PMID- 22132593
TI  - Outcomes of patients presenting to a dedicated rapid access lung cancer clinic.
AB  - We examined the outcomes of the first 500 patients referred to a dedicated Rapid
      Access Lung Cancer Clinic. A total of 206 patients (41.2%) were diagnosed with a
      thoracic malignancy; 179 had primary lung cancer and 27 had secondary or other
      thoracic cancers. Pulmonary nodules requiring ongoing surveillance were found in
      a further 79 patients (15.8%). Of those patients found to have primary lung
      cancer, 24 (13.4%) had Small Cell and 145 (81%) had Non Small Cell Lung Cancer.
      In patients with Non small cell tumours, 26 (21.1%) were stage 1, 14 (11.4%)
      stage II, 37 (30.1%) stage III and 46 (37.4%) stage IV at diagnosis. For the 129
      patients (72%) in whom the thoracic MDT recommended active treatment, primary
      therapy was surgical resection in 44 (24.6%), combined chemoradiation in 31
      patients (17.3%), chemotherapy alone in 39 (21.8%) and radiation in 15 (8.4%).

PMID- 22132594
TI  - A comparison of Gaelic football injuries in males and females in primary care.
AB  - The Ladies Gaelic Football Association has a playing population of 150,000 of
      which 33% are adults. A number of studies have been published on rates of injury
      among male athletes but none on female athletes in Gaelic football. A
      retrospective review of insurance claims, submitted under the Gaelic Athletic
      Association Player Insurance Injury Scheme. 405 injuries were recorded, 248 [107
      (70%) male, 141 (58%) female] to the lower limb, 91 [33 (21%) male, 58 (23%)
      female] to the upper limb. The majority of lower limb injuries [56 (52%) male, 56
      (40%) female] were to muscle. Almost a third of upper limb injuries were
      fractures [10 (30.3%) male, 33 (57%) female]. injuries/1000 hours playing was
      8.25 for men and 2.4 for women. The injury rate in ladies Gaelic football was
      found to be significantly lower than in men's Gaelic football. Lower limb
      injuries accounted for the majority of injuries in both sports.

PMID- 22132595
TI  - Are women in early pregnancy following the national pyramid recommendations?
AB  - Appropriate nutrition in pregnancy is fundamental for maternal and fetal health,
      and the long-term physiological wellbeing of the offspring. We aimed to determine
      whether a sample of pregnant women met the national guidelines for healthy eating
      during pregnancy, and to examine if compliance differs when analysed by Body Mass
      Index (BMI) category. Subjects completed a 24-hr dietary recall, and had their
      BMI calculated. The mean age was 27.8 years. The mean BMI was 25.1 kg/m2, with 32
      (31.7%) subjects overweight and 14 (13.9%) obese based on BMI category. Although
      the majority of subjects thought that they had a healthy diet, less than half met
      the recommended guidelines for each individual food group with achievement of the
      dairy group being particularly low. Achievement of food group recommendations was
      not influenced by BMI category. Public health messages on healthy eating
      guidelines need to be clearly communicated to pregnant women.

PMID- 22132596
TI  - Assisted admissions? A national survey of general practitioner experience of
      involuntary admissions.
AB  - The 2001 Mental Health Act introduced in 2006, changed how a patient is admitted
      involuntarily to a psychiatric unit. This paper reports on a national survey of
      general practitioners' experience implementing the Act. Five hundred and sixty
      eight (568) GPs completed the survey. Twenty five percent (25%) of respondants
      had not used it. When used, twenty four percent (24%) report that it takes seven
      hours or more to complete an admission. Fifty percent (50%) of respondents are
      confident to complete the necessary paperwork. Overall GPs are dissatisfied with
      arrangements for transport of patients (mean Likert score 3.5), primarily due to
      the time delay. GPs believe this places risk on the patient, family and GP. Only
      thirty-three percent (33%) of respondents feel that the Mental Health Act has
      improved the patient, GP and family experience of involuntary admission.

PMID- 22132597
TI  - Is laparoscopic appendicectomy a safe procedure for trainees in the peripheral
      hospital setting?
AB  - Laparoscopic appendicectomy has become standard in the treatment of acute
      appendicitis in most hospitals in Ireland. Studies have shown that it is a safe
      procedure for trainees to perform. However, these studies were conducted in
      university teaching hospitals whereas a significant proportion of training in
      Ireland takes place in peripheral hospitals which provide a different training
      environment. The aim of this study was to determine whether laparoscopic
      appendicectomy is a safe procedure for surgical trainees to perform in a
      peripheral hospital setting. A retrospective analysis was performed of
      appendicectomies carried out at a peripheral hospital over a 12 month period.
      Comparisons were made between consultant surgeons and trainees for a variety of
      outcomes. Of 155 appendicectomies, 129 (83.2%) were performed laparoscopically,
      of which 10 (7.75%) were converted to open. Consultants performed 99 (77%)
      laparoscopic appendicectomies. There were no statistically significant
      differences between consultants and trainees in complication rates (19 (19.2%)
      vs. 4 (13.3%), p = 0.46), mean length of hospital stay (4.7 +/- 4.0 vs. 3.4 +/-
      3.3 days, p = 0.13), or rate of conversion to open operation (9 (9.1%) vs. 1
      (3.3%), p = 0.45). For cases of complicated appendicitis there were no
      significant differences between consultants and trainees in complication rates
      (12 vs. 2, p = 0.40) or length of hospital stay (6.4 +/- 3.9 vs. 4.7 +/- 5.6
      days, p = 0.27). We conclude that laparoscopic appendicectomy is a safe procedure
      for trainees to perform in the peripheral hospital setting and should be
      incorporated into surgical training programs at an early stage of training.

PMID- 22132598
TI  - Not for resuscitation: more harm than good?
AB  - Advance directives such as do not resuscitation orders are becoming more common
      place in Irish Hospitals. A questionnaire was completed by all 44 interns working
      in St James' Hospital in January 2010 and by 49/50 Senior House Officers in June
      2010.3/44 of interns (6%) and 5/49 (10%) SHO believe that there is no difference
      between palliative patients and NFR patients. 41/44 interns (93%) and 40/49 of
      SHOs (81%) believe that attitudes of treating staff change once a patient is
      listed as NFR. 14/44 of Interns (32%) and 15/49 SHOs (31%) think that nursing
      staff are reluctant to request a review when these patients become unwell. They
      were asked if someone listed as NFR became unwell, what would be an appropriate
      intervention using a grading system. Interns and SHOs appeared to be reluctant to
      make basic interventions such as blood tests, blood cultures or even oral
      antibiotics in this sub group of patients. This questionnaire demonstrates that
      NFR patients are potentially treated differently and possibly under treated by
      Junior Doctors. The question remains how to balance the best interests of the
      patient. If NFR status results in under treatment does it cause more harm than
      good.

PMID- 22132599
TI  - Variations in the usage and composition of a radial cocktail during radial access
      coronary angiography procedures.
AB  - A survey was conducted of medication administered during radial artery
      cannulation for coronary angiography in 2009 in Ireland; responses were obtained
      for 15 of 20 centres, in 5 of which no radial access procedures were undertaken.
      All 10 (100%) centres which provided data used heparin and one or more anti
      spasmodics; verapamil in 9 (90%), nitrate in 1 (10%), both in 2 (20%). There were
      significant variations in the doses used. Further work needs to be done to
      determine the optimum cocktail to prevent radial artery injury following coronary
      angiography.

PMID- 22132600
TI  - Spontaneous spinal epidural abscess.
AB  - Spinal epidural abscess is an uncommon entity, the frequency of which is
      increasing. They occur spontaneously or as a complication of intervention. The
      classical triad of fever, back pain and neurological symptoms are not always
      present. High index of suspicion is key to diagnosis. Any delay in diagnosis and
      treatment can have significant neurological consequences. We present the case of
      a previously well man with a one month history of back pain resulting from an
      epidural abscess.

PMID- 22132601
TI  - Paediatricians' views on their role in the assessment and management of ADHD and
      autism.
AB  - ADHD and Autistic Spectrum Disorders (ASD) are a core component of paediatricians
      case work in the U.K. and U.S., but the situation in Ireland is less clear. Due
      to significant underdevelopment of Child and Adolescent Mental Health Services in
      Ireland, long waiting lists may delay identification and treatment. The aim of
      our study was to explore the views of a group of paediatricians in relation to
      their current and future practice of assessing and managing ADHD and ASD. The
      outcome of our study indicated that more than half of the paediatricians surveyed
      are directly involved in the assessment or treatment of ADHD and ASD. Eighty five
      per cent (85%) of paediatricians believed that they should have a role in the
      assessment of ADHD and ASD and over half had thought that they should be involved
      in managing ADHD and ASD. These results suggest that there is potential to
      develop alternative specialist services in Ireland for the identification and
      treatment of children with ADHD and ASD. The development of a well coordinated
      integrated care pathway may reduce waiting times for families and lead to easier
      access to services.

PMID- 22132602
TI  - Outpatient clinic reminders.

PMID- 22132603
TI  - Zinc deficiency in a breast-fed baby.

PMID- 22132604
TI  - Severe symptomatic hyponatremia.

PMID- 22132605
TI  - Irish Childhood National Diabetes Register.

PMID- 22132606
TI  - Range of emotions: caring for victims of spousal abuse.

PMID- 22132607
TI  - Is baby-friendly certification nurse friendly?

PMID- 22132608
TI  - Funding delivery, finding value.

PMID- 22132609
TI  - Bedside capnography: better management of surgical patients with obstructive
      sleep apnea.

PMID- 22132610
TI  - Pilot project to provincial program: sustaining safe babies.

PMID- 22132611
TI  - Fertility nurses: giving mother nature a helping hand.

PMID- 22132612
TI  - Good business practices.

PMID- 22132613
TI  - Make sure you question.

PMID- 22132614
TI  - [Perspectives of health care and system of health services].
AB  - Health services are more expensive year by year and chronic diseases are more
      frequent. It is obvious that coping with health problems predominantly in
      hospitals is not effective. That is why there are attempts to involve all people
      in health care. Article explains possibilities of health services rationing,
      importance of health literacy and social determinants of health. People and their
      health are key elements of any health care system and are important for
      successful social and economic development.

PMID- 22132615
TI  - [Strategic dominance of the mucosal immune system in the defence and tolerance].
AB  - Mucosal immune system is functionally characterized by its ability to limit the
      access of environmental antigens such as food, airborne materials, and commensal
      microbes to the systemic immune compartment, leading to reduction in the
      magnitude of systemic immune responses. Mucosal immune system reacts at the site
      of antigen exposure and at anatomically distant mucosal sites by specific
      antibodies production and specific cellular immunity. The mucosal administration
      of neoantigen induces specific mucosal and systemic antibodies production and
      systemic effector T cells anergy accompanied by induction of regulatory T cells,
      phenomenon termed mucosal tolerance. Based on above observations, several studies
      test the ability to prevent some autoimmune diseases by mucosal administration of
      respective antigens but with little to no success. This review attempts to
      describe mechanisms involved in the induction of immune response and tolerance
      after immunization by mucosal routes - oral or intranasal administration. Further
      it aims to elucidate conditions critical for elicitation of mucosal tolerance.

PMID- 22132616
TI  - [The impact of neuroprotection on brain metabolism during carotid
      endarterectomy].
AB  - BACKGROUND: The primary objective of this study was to evaluate the impact of
      neuroprotection, administered during carotid endarterectomy, on brain metabolism.
      The secondary objective was to assess the impact on clinical outcome of the
      resulting changes to brain metabolism. METHODS: A total of 35 patients underwent
      carotid endarterectomy with prophylactic combined neuroprotection (Sendai
      cocktail: Manitol, Phenhydan, Solumedrol, Tokoferol; Cerebrolysin; fraction of
      inspired oxygen (FiO2) = 1, middle arterial pressure (MAP) = 100 mm Hg, total
      intravenous anaesthesia--TIVA). The influence of neuroprotection on brain
      metabolism (S100B, glycaemia, lactate, pH, jugular vein bulb oxygen saturation-
      SvjO2) was evaluated. Metabolic parameters were acquired from the jugular bulb
      during surgery, just before unclamping of the vessel. The clinical outcome was
      evaluated by NIHSS (National Institutes of Health Stroke Scale). There were 35
      patients in the control group who where operated on without any neuroprotection.
      The results from both groups of patients were compared and statistically
      analyzed. RESULTS: Postoperative NIHSS did not change in any patients in either
      group. An intraoperative shunt was not inserted in any patients in either group.
      In the group with neuroprotection there were significantly higher levels of S100B
      (median 0.117 vs. 0.088; p < 0.0182), lactate (median 1.92 vs. 1.020; p <
      0.0006), glycaemia (median 9.5 vs. 8.2; p < 0.0243), and SvjO2 (median 0.79 vs.
      0.65; p < 0.0001). There were no postoperative changes to NIHSS in either group.
      CONCLUSIONS: Neuroprotection administered before carotid endarterectomy
      influences some parameters of brain metabolism both positively and negatively,
      but with no impact on clinical outcome.

PMID- 22132617
TI  - [Problems with placement and using of automated external defibrillators in Czech
      Republic].
AB  - The use of automated external defibrillators improves the survival of adults who
      suffer from cardiopulmonary arrest. Automated external defibrillators detect
      ventricular fibrillation with almost perfect sensitivity and specificity. Authors
      describe the use of automated external defibrillator during cardiopulmonary
      resuscitation in a patient with sudden cardiac arrest during ice-hockey match.
      The article reports also the use of automated external defibrillators in
      children.

PMID- 22132618
TI  - [Human dignity and medical ethics].
AB  - The concept of human dignity and the respect to it have issued from various
      sources--philosophical, religious and cultural. The text deals with the thinking
      of some philosophers (intrinsic dignity versus attributed dignity), with
      religious thoughts (explaining the dignity of man as being created in God's
      image) and discusses the important declarations, especially the Universal
      Declaration of Human Rights. This declaration (UN, 1948) recognizes, in consent
      with both--the best philosophical tradition and biblical faith, the inherent
      dignity and worth of every human being (person); it is the first principle and
      the inescapable grounding for all human rights. The term human dignity is hotly
      debated in the present bioethics arena; nevertheless it is the source of
      considerable and dangerous confusion as well. Some bioethicists deny implicitly
      or even explicitly the dignity of every human being (they conflate intrinsic and
      attributed dignity), and others proclaim that dignity is a useless concept. But
      the respect to human dignity is the cornerstone of all medical ethics--this
      discipline will be changed into ethical parody without it. It is therefore
      necessary to see the problems in the broader context and to stand firmly on the
      right side of the dispute: on the side of each and every patient.

PMID- 22132619
TI  - [Preparation of the Eighth Framework Programme of the European Union--Health
      Priority. European Commission organizes proposal of aims in biomedical research
      prospecting to 2020].
AB  - Eighth framework programme (FP8) of the European Union for years 2014-2020
      undergoes the preparatory process. The overview presents current status of the
      programme preparation. European Commission organized three workshops (-omics in
      personalised medicine, 4D biology for health and disease, and Stratification
      biomarkers in personalised medicine) with the purpose to bring together experts
      from different fields to build a 2020 vision, and to identify the research needs
      for next years.

PMID- 22132620
TI  - [Extraesophageal reflux disease].

PMID- 22132621
TI  - [Women's hygiene III. The second half of 17th and 18th century].

PMID- 22132622
TI  - [Max Ludwig Henning Delbruck (1906-1981)].

PMID- 22132623
TI  - [Biochemical mechanisms of action of antidepressants].
AB  - The findings regarding direct, early and long-term biochemical effects of
      antidepressants are summarized in this review. Mechanisms of action of other
      drugs showing antidepressant activity are mentioned as well as alternative
      possibilities of adjuvants. Psychotropic drugs used in the therapy of mood
      disorders show neurotrophic or neuroprotective effects after long-term treatment.
      Thus, next to adenylate cyclase, guanylate cyclase, phosphoinositide and calcium
      systems, attention has been paid to tyrosine kinase pathway and Wnt pathway.
      Knowledge about biological markers of mood disorders and predictors of efficiency
      of pharmacotherapy is included also in relation to importance, potentialities and
      perspectives in the development of new antidepressants.

PMID- 22132624
TI  - [Hypophosphatasia--biochemical and clinical manifestations, molecular genetic
      principles].
AB  - Hypophosphatasia is a rare hereditary metabolic disorder accompanying deficit of
      tissue nonspecific serum alkaline phosphatase. The incidence of overt forms is
      estimated about 1:100000 live births. In the prenatal manifestation the disease
      may cause severe damage to the foetus with intrauterine death. In children there
      is a defect of mineralization with rickets signs and the subsequent
      hypercalcaemia a hypercalciuria may lead to death. In adults the main
      manifestation is osteomalacia, skeletal deformities and fractures, early
      arthritis. In severe forms the heredity is autosomal recessive type. In mild
      forms the heredity may be dominant or recessive. In two case reports we present
      clinical course of the disease in two adult sisters, where diagnosis of
      hypophosphatasia was first time confirmed in Slovak population using molecular
      genetic methods.

PMID- 22132625
TI  - [Post-traumatic panniculitis (decubitus ulcer?) of the breast--a clinical case].
AB  - The authors describe the case of an eighty-year-old woman. Several hours of
      pressure on the right breast during a coma was the cause of inflammation which
      appeared to be phlegmon or inflammatory breast cancer. Histological examination
      excluded a malignant process and general treatment was to administer
      corticosteroids with antimicrobial drugs which resulted in the recovery of the
      patient.

PMID- 22132626
TI  - [New proposal of the medical criteria for assessing the stage dependency care
      regarding the need of the care benefit].
AB  - The article informs about the new proposal of the medical criteria for assessing
      the stage dependency care regarding the need of the care benefit according to the
      social service law. The new criteria were designed in accordance with assessment
      of the Activities of daily living and the principles of the International
      Classification of Functioning, Disability and Health.

PMID- 22132627
TI  - [Conflict of interest: the World Medical Association statement].
AB  - This article presents a translation of the World Medical Association Statement on
      Conflict of Interest (2009) and Statement concerning the Relationship between
      Physicians and Commercial Enterprises (2009). The introduction illuminates the
      objectives of this recommendation in the context of healthcare in the Czech
      Republic.

PMID- 22132628
TI  - [Women's hygiene IV. 19th century].

PMID- 22132629
TI  - [100th anniversary of the foundation of Institute of Biology and Medical Genetics
      of the First Faculty of Medicine, Charles University and General University
      Hospital].

PMID- 22132630
TI  - [Nobel Prize laureates. Alfred Day Hershey (1908-1997)].

PMID- 22132631
TI  - [Dr. Josef Jerie, founder of Czechoslovak gynecology and obstetrics (1871-1951].

PMID- 22132632
TI  - [Follow-up after conservative surgery for cervical precancer lesions].
AB  - OBJECTIVE: To summarize current knowledge of postoperative follow-up after
      conservative surgical treatment of cervical precancer lesions. DESIGN: Review
      article. SETTING: Oncogynecological center, Department of Gynecology and
      Obstetrics, General Faculty Hospital and 1st Medical School of Charles
      University, Prague. METHODS AND RESULTS: Residual or recurrent disease is
      diagnosed in a small amount of women after conservative surgical treatment of
      cervical precancer lesions. Series of consecutive negative findings are necessary
      prior to return back to routine screening. Most sensitive marker for residual and
      recurrent disease is detection of HPV infection. Negative predictive value of HPV
      testing is significantly higher as compared with negativity of surgical margins
      or negative Pap smear. CONCLUSIONS: Combination of HPV and Pap smear negativity
      shows nearly absolute negative predictive value for oncologically relevant
      finding in postoperative management.

PMID- 22132633
TI  - [Basic anthropometric characteristics and their relationship with the metabolism
      of saccharides in women with PCOS].
AB  - AIM OF STUDY: To determine basic anthropometric characteristics and their
      relationship with the metabolism of saccharides in women with PCOS in the Olomouc
      region. TYPE OF STUDY: Retrospective study of the results of 72 women with PCOS
      examined in the endocrinology clinic. MATERIAL AND METHOD: The study entailed the
      processing of data gained on the basis of examination of women sent to
      endocrinology clinic for examination in the years 2008-2010, who corresponded to
      the diagnostic criteria for PCOS according to the Rotterdam consensus. The
      obtained results of anthropometric measurement and characteristic saccharide
      metabolism were compared with a group of healthy women. RESULTS: In groups of
      women of comparable age (PCOS average age 31.6, control group average age 31.4)
      the average BMI in women with PCOS was 26.76 kg m(-2), the average waist
      measurement was 84.43 cm, the waist/hips ratio was 0.79, in the control group the
      average BMI was 24.73 kg m(-2), the waist/hips ratio was 0.76, the differences
      between the two groups were not statistically significant. There was a
      statistically significant difference between women with PCOS and the healthy
      control group in C peptide values, even in comparable anthropometric parameters.
      Levels of fasting glycaemia and glycated haemoglobin were comparable. Waist
      measurement, as a parameter for evaluating the level of visceral accumulation of
      fat in women with PCOS, was related to all monitored characteristics of
      saccharide metabolism (statistically significant correlation with fasting
      glycaemia, glycated haemoglobin and C peptide). Unlike the waist measurement, the
      waist/hips ratio indicated a smaller percentage of women with abnormal obesity in
      both groups, in women with PCOS it correlated with fasting glycaemia and C
      peptide. CONCLUSION: On the basis of our results it can be stated that women with
      PCOS do not necessarily differ from the healthy control group in anthropometric
      parameters. However, with comparable age, BMI and level of visceral obesity,
      women with PCOS require a greater amount of insulin to maintain normoglycaemia
      than healthy women.

PMID- 22132634
TI  - [Evaluation of initial experience with safety and short efficacy of mini-sling
      antiincontinence procedures MiniArc and AJUST system].
AB  - OBJECTIVE: The aim of our study is to present initial experiences, with regard to
      safety and short-term efficacy, of mini-sling MiniArc and AJUST operations for
      stress urinary incontinence (SUI). DESIGN: Cross-sectional clinical study.
      SETTINGS: Gynecological and Obstetric Clinic 1. LF UK and VFN Prague;
      Gynecological and Obstetric Clinic FN Bulovka and 1. LF UK Praha; Urological dpt.
      FTN Prague; GONA spol. s r.o.; Urological dpt. FN Ostrava Poruba. MATERIALS AND
      METHODS: We present briefly the technique employed in the operations, the
      urodynamic examination procedure before and after the operation, and the
      subjective and objective outcomes of these procedures from the 5 above-mentioned
      hospitals which participated on the study. Objectively the leakage of urine was
      assessed during urodynamic examination and by cough test. Subjectively leakage of
      urine was assessed by ICIQ-SF questionnaire (The International Consultation on
      Incontinence, short form). This study evaluated the cure effect and complications
      accompanying the MiniArc and AJUST procedures, and compared these results. The
      clinical study included 66 women with previously untreated stress urinary
      incontinence. These women were randomly divided by envelop method into two
      groups; the first group of patients underwent operations using the MiniArc (n=33)
      technique and the second group the AJUST (n=33) technique. Mean age was 57.9
      years in the AJUST group and 57.7 years in the MiniArc group. Mean body mass
      index (BMI) was 29.2/28.7 in the AJUST/MiniArc groups respectively, and mean
      parity was 2.09/2.24. We did not find statistically significant differences
      between these two groups. RESULTS: The curative rate of the MiniArc and AJUST
      procedure was evaluated 3 months after the operation (+/- 1 week). We can
      conclude from the outcomes of the cough test that this test was negative in 61
      (92%) of patients overall; in the AJUST group it was 31 (94%) of patients and in
      the MiniArc group 30 (91%) of patients. In the subjective evaluation of the
      leakage of urine before operation (ICIQ-SF) the mean score in the group of
      patients who subsequently underwent the AJUST operation was 15.4 (SD-3.39; median
      16, range 8-21) and in women who underwent the MiniArc operation it was 15.5 (SD
      3.3; median-16, range 8-21). The AJUST/MiniArc procedure caused a statistical
      significant decrease in the total score to -14.09(SD-5.18)/-14.45 (SD-3.73). The
      difference in the decrease of the score between the AJUST/MiniArc groups was not
      statistically significant. In the AJUST group of patients, according to the ICIQ
      SF, 30 (91%) women were without problem or improved [27 (81.7%) of women were
      without problem], while in the MiniArc group 32 (96.9%) were without problem or
      improved [24 (72.7%) of women were without problem]. The urodynamic examination
      before and after operation indicated that there were no differences between the
      groups of patients either before and or after the operation. Changes in the
      parameters MUCP, Qmax and others caused by the operation were not significant,
      and there were no statistical significant differences in the values of these
      parameters between the groups of patients. Complications of the MiniArc and AJUST
      procedures were not recorded. CONCLUSIONS: Our first experiences with MiniArc and
      AJUST procedures, including possible complications and curative rate, are
      positive. From the preliminary results the cure effect of MiniArc and AJUST 3
      months after the operation (+/- 1 week) is similar. It will be important to
      evaluate the efficacy of these procedures one year after the operation for a
      definitive evaluation of the cure effect.

PMID- 22132635
TI  - [Axillary reverse mapping--chance to prevent lymphedema in breast cancer
      patients].
AB  - OBJECTIVE: The axillary reverse mapping (ARM) technique has been developed to map
      and preserve arm lymphatic drainage during axillary lymph node dissection (ALND)
      and/or sentinel lymph node (SLN) biopsy, thereby minimizing arm lymphedema.
      However, several problems remain to be resolved in the practical application of
      this technique. This article presents a review of current knowledge regarding ARM
      and discusses the practical applicability and relevance of this technique. TYPE
      OF STUDY: Review. SETTING: Oncogynecologic center, Gynecology-Obstetrics Clinic,
      1st Medical Faculty and General Teaching Hospital, Prague. CONCLUSIONS: The
      axillary reverse mapping (ARM) procedure is based on the hypothesis that the
      lymphatic drainage from the upper arm is different from that of the breast and
      offers the opportunity to prevent lymphedema in breast cancer patients. However,
      the oncologic safety of the procedure has not yet been determined.

PMID- 22132636
TI  - [Current classification of malignant tumours in gynecological oncology--part II].
AB  - OBJECTIVE: Review of new staging systems for gynaecological cancers and their
      impact on prognosis and planning treatment. DESIGN: Review article. SETTING:
      Department of Gynaecology and Obstetrics, First Faculty of Medicine and
      University Hospital Na Bulovce, Charles University, Prague; Department of
      Radiotherapeutic Oncology, First Faculty of Medicine and University Hospital Na
      Bulovce, Charles University, Prague; Department of Pathology, University Hospital
      Na Bulovce, Prague. RESULTS: Every staging system should have 3 basic
      characteristics: it must be valid, reliable, and practical. Over the years, these
      staging classifications--with the exception of cervical cancer and gestational
      trophoblastic neoplasia--have shifted from a clinical to a surgical-pathological
      basis. Changes based on new findings were proposed in 2008 by the FIGO Committee
      on Gynecologic Oncology, approved in September 2008 by the FIGO Executive Board,
      and published in 2009. The greatest changes were made in the new staging system
      for carcinoma of the vulva and others in the new staging systems for carcinoma of
      the cervix and carcinoma of the endometrium. A new stanging system was also
      created for uterina sarcomas, based on the criteria used in other soft tissue
      sarcomas. A clinical staging system for carcinoma of cervix continues because
      surgical staging cannot be employed worldwide (especially in third world
      countries). Stage 0 has been deleted from the staging of all tumours, since it is
      pre-invasive lesion and it is not an invasive tumour. In the revised staging
      system for carcinoma of the endometrium, four fundamental changes have occurred,
      which will be discussed. Carcinosarcoma is still staged identically to carcinoma
      of the endometrium. A completely new staging system was created for
      adenosarcomas, along with an almost identical staging system for leiomyosarcoma
      and endometrial stromal sarcoma. The staging system for carcinoma of ovary and
      Fallopian tube remains without changes. CONCLUSION: Since medical research and
      practice in the field of oncology have shown explosive growth, the staging of
      some of the gynaecological cancers did not give a good spread of prognostic
      groupings. Therefore, revised FIGO and TNM staging system has been structured to
      represent major prognostic factors in predicting patients' outcomes and lending
      order to the complex dynamic behavior of gynaecological cancers. The purpose of
      good staging system is to offer a classification of the extent of gynaecological
      cancer in order to provide a method of conveying one's clinical experience to
      others for the comparison of treatment methods.

PMID- 22132637
TI  - [Thrombin generation test at physiological and risk gravidity].
AB  - Generation of thrombin is pivotal step of hemostasis, according to in vitro
      experiments, thrombin generation occurs in 2 phases. Initially small amount of
      thrombin is produced after activation of factor X by complex TF/FVIIa. Thrombin
      multiplies coagulation by activation of platelets, F V a F VIII. Complex of
      TF/FVIIa activates also F VIII a, F IX, F VIII and FIXa and its binding to
      surface of platelets, which activates F X and products quantity of thrombin and
      leads formation of fibrin and finaly to triggering clotting. DESIGN: Review.
      SETTING: Department of Obstetrics and Gynecology, University Hospital Olomouc.

PMID- 22132638
TI  - [Names and eponyms in Italy obstetrics and gynaecology].

PMID- 22132639
TI  - Hormonal contraception after intrahepatic cholestasis of pregnancy.
AB  - OBJECTIVE: Comparing the use of oral contraception (OC), treatment side effects
      and the incidence of cholecystolithiasis in women with a history of intrahepatic
      cholestasis of pregnancy (ICP), before and after introducing ursodeoxycholic acid
      (UDCA) in the treatment. DESIGN: Regional epidemiological. SETTING: Department of
      Obstetrics and Gynecology, General Hospital, Trencin, Slovak Republic. METHODS:
      Retrospective analysis of 79 deliveries with ICP between 1992 and 2004. Group 1
      included 36 women who delivered between 1992 and 1996 and were not treated by
      UDCA. Group 2 included 43 women who delivered between 1997 and 2004 and were
      managed with a 500-750 mg daily dose of UDCA administered orally. In 2008, the
      questionnaire was sent to all treated women with ICP. The analysis was focused on
      OC use and presence of cholecystolithiasis, or cholecystectomy in individual
      groups. The incidence of difficulties comparable to ICP was analyzed in OC users.
      RESULTS: The frequency of ICP was the same in both groups (0.4% of deliveries).
      The questionnaire response rate was 71%. Analysis was conducted in 56 women with
      ICP--in Groups 1 and 2 it was 26 and 30 women, respectively (the difference
      statistically insignificant, p=0.81). In the observed population, 15 women
      (26.8%) used hormonal contraception--in Groups 1 and 2 it was 42.3% and 13.3%,
      respectively (statistically significant difference, p=0.015). Only one woman in
      Group 1 reported pruritus during the use of OCs. The frequency of
      cholecystolithiasis or cholecystectomy occurrence was 26.8% in the entire
      population--in Groups 1 and 2 it was 38.5% and 16.7%, respectively (statistically
      significant difference, p=0.043). CONCLUSION: Based on our results it is possible
      to consider the use of OC in women with a history of ICP as safe. Only a minimum
      of side effects have been recorded in relatively high percentage of OC users.

PMID- 22132640
TI  - [Perineal audit: reasons for more than one thousand episiotomies].
AB  - AIM: To analyze reasons for episiotomy use in vaginal delivery among
      obstetricians and midwives. Consecutively, to indentify disputable indications
      for its use based on published research in order to facilitate the decrease in
      frequency of this operation, while preserving high quality of obstetrical care.
      METHODS: Reasons for mediolateral episiotomy use were recorded by obstetricians
      and midwives after each vaginal delivery with episiotomy at the Ob&Gyn Department
      of the Charles University Hospital in Pilsen in the period of February 2006 -
      June 2007. The main reason and all reasons for episiotomy use were evaluated
      separately. RESULTS: The reason for episiotomy use was recorded in 1069 cases
      (93%) out of a total of 1150 vaginal deliveries, in which mediolateral episiotomy
      was performed (42% of all vaginal deliveries). The most common group of main
      reasons for episiotomy use was a concern about postpartum pelvic floor functional
      impairment (624, 58% of episiotomies), especially a rigid, non-elastic perineum
      (401, 37%). Fetal distress (181, 17%) and abnormalities of the expulsive
      forces/uncooperative parturient (109, 10%) followed. When evaluating all
      (including secondary) reasons, the most common groups of reasons for episiotomy
      use were the effort of pelvic floor functionality preservation (871, 50%),
      abnormalities of the expulsive forces/uncooperative parturient (354, 20%) and
      fetal distress (253, 15%). When evaluating episiotomies performed by
      obstetricians and midwives separately, the concern about postpartum pelvic floor
      functionality prevailed in midwives (81% vs. 39% of episiotomies performed
      primarily for this reason). Conversely, the obstetricians performed episiotomy
      more frequently for fetal distress (28% vs. 4%). CONCLUSION: In view of the fact
      that midwives attend only physiological deliveries in our department, the
      spectrum of reasons for episiotomy use among midwives is narrower and the concern
      about postpartum pelvic floor functionality dominates. Currently, the concern
      about postpartum pelvic floor functionality should not be considered a legitimate
      indication for episiotomy use. The fact that 624 (58%) episiotomies were
      performed for this reason represents a significant reserve for a decrease in the
      frequency of episiotomy use. The reduction should be possible primarily among
      midwives (81% of all main reasons for episiotomy use in the midwive group, i.e.
      37% of all episiotomies performed). The analysis of reasons for episiotomy use is
      an important step in reduction of episiotomy rates while preserving or improving
      the standard of treatment provided.

PMID- 22132641
TI  - [Risk factors in the medical history of pregnant women undergoing congenital
      heart defect prenatal screening].
AB  - AIMS: Evaluation of the congenital heart defects (CHDs) incidence and their
      prenatal detection rate in the Moravian-Silesian region. Presentation of fetal
      echocardiography as a screening method. Investigation of the relationship between
      risk factor and congenital heart defects. METHODOLOGY: Long-term study between
      1999-2009. Overall evaluation of CHDs incidence and their follow-up and analysis
      of their link to possible risk factors. The data were collected from medical
      notes of the gynecologist and pediatric cardiologist in the region. Fetal
      echocardiography was performed as a primary screening during the second term of
      pregnancy. A number of 22 743 pregnant women were included in the study. When any
      pregnancy pathology detected, more detailed examination followed (extracardial
      diseases, chromosomal aberrations). RESULTS: In the observed period, there were a
      total of 453 significant CHD (3.55/1000 births). In prenatal phase 208 CHDs
      (45.9%) were diagnosed. At least one risk factor was mentioned in 15.9 % of the
      screened families. When compared with the group without and with any risk factor,
      the difference is significant (chi=7.28, p<0.0001). Mothers younger than 35 were
      compared with those aged 35 and older and the difference in values was not
      significant. However, generally, the probability of CHDs grow with age (GLM,
      z=2.468, p=0.013). CONCLUSIONS: Prenatal detection of CHDs has the highest
      success rate as a rutine screening method during the second trimester of
      pregnancy. We confirmed the existence of a higher occurrence of the CHD in the
      group of pregnant women with a history of risk factors in comparison with the
      group without such a history. The risk families should be offered a detailed
      examination by paediatric cardiologist skilled in fetal echocardiography. Heart
      defects are the most common morphology anomalies, mostly occuring as an isolated
      issue.

PMID- 22132642
TI  - [Fetal hypotrophy dopplerometry].
AB  - OBJECTIVE: The aim of the study was the longitudinal analysis of the progression
      of dopplerometric abnormalities in intrauterine growth retardation (IUGR) since
      the onset of placental insufficiency. DESIGN: Prospective study. SETTING: Dept.
      of Gynaecology and Obstetrics, Medical Faculty and University Hospital, Olomouc.
      METHODS: The study group consisted of 77 pregnat women with intrauterine growth
      retardation resulting from placental insufficiency. Of these, in 59 women, the
      intervals of progression were followed from the early to the advanced
      dopplerometric abnormalities. According to the findings the patients were
      classified into one of the three types of placental insufficiency. RESULTS: In
      total, 486 dopplerometric measurements in 77 pregnant patients were performed.
      Mild placental insufficiency where abnormality of umbilical artery (UA) and
      cerebroplacental ratio (CPR) did not exceed 3 SD and the progressive interval was
      31 days was found in 21 pregnat patients. Progressive placental insufficiency
      with a whole spectrum of abnormalities and the progressive interval of 18 days
      was found in 28 pregnat patients. Severe form of placental insufficiency (early
      onset of abnormalities before the 30th gestational week) a whole spectrum of
      abnormalities and progressive interval 8 days was found in 10 pregnat patients.
      CONCLUSIONS: Gestational week at the occurence of the first abnormality
      (elevation of the pulsatility index of UA over 2 SD) and the time interval to
      next abnormality (decrease of CPR under 2 SD) are important factors for the
      assessment of severity of placental insufficiency. Dynamic follow-up of
      abnormalities permits a better evaluation of the actual risk, the anticipation of
      the further development of placental insufficiency and in this way to apply
      suitable measures to prevent unfavourable perinatal outcomes.

PMID- 22132643
TI  - [Single embryo transfer--possibilities and limits].
AB  - OBJECTIVE: To evaluate the results of single embryo transfers, on a set of
      patients, for a given period of time. DESIGN: Retrospective study. SETTING:
      Pronatal Sanatorium, Prague. METHODS: Between January 2008 and May 2010, we
      evaluated the results of all cycles with single embryo transfers in our
      workplace. There were four groups of patients: the first group with elective
      single embryo transfers (ESET, n=147), the second group with only a single embryo
      transfer without selection (SET n=269), the third group with transfer of one
      embryo derived from the native cycle (NC, n=70) and the last group with transfer
      of only one embryo examinated by preimplantation genetic diagnosis (PGD, n=104).
      All patients were monitored by age, length of cultivation of embryos, clinical
      pregnancy rate/transfer (CPR/ET), pregnancy loss (AB) and baby take home rate
      (BTR). Statistical evaluation was performed using the chi square test. RESULTS:
      The group with ESET achieved a significantly higher success rate (50% CPR/ET,
      p<0.001) compared to the other groups: 22% for SET, 7% of spontaneous cycles and
      18% after PGD. A significant difference (p<0.001) was also apparent in the
      evaluation of BTR: ESET 41%, 16% SET, NC 4%, 12.5% of PGD. Patients that made
      ESET were significantly younger (p<0.001) compared to the other monitored groups
      (32.9 ESET, SET 35.2, NC 39.6, 39.1 PGD). CONCLUSION: We consider that assisted
      reproduction is only successful with the birth of one healthy child. For women 38
      years old or younger the most successful treatment is to transfer a single high
      quality embryo and to therefore eliminate multiple pregnancy. The age of a woman
      and the quality of the embryo are major prognostic factors.

PMID- 22132644
TI  - [DMEK (Descemet membrane endothelial keratoplasty)--early and late postoperative
      complications].
AB  - The authors refer to the cross-sectional study of surgical technique, operation,
      early and late postoperative complications in the first 30 patients after DMEK
      (Descemet membrane endothelial keratoplasty). SETTING AND METHODS: The group
      comprised 17 women and 13 men with an average age of 62 years (SD 12.2). The
      follow up period 1-12 months, average 4.2 months. The DMEK were indicated in
      patients with boullous keratopathy, Fuchs' endothelial dystrophy and endothelial
      insufficiency after repeated corneal transplantation. RESULTS: In half of the
      patients had to undergo DMEK surgery and the other half DMEK surgery combined
      with cataract surgery. One patient dropped from the Descemet membrane
      transplantation because of insufficient donor cornea and was indicated re DMEK.
      SURGICAL COMPLICATIONS: 4 times difficulty of the striping of Descemet membrane,
      2 times operating decentration plates, 1 times bleeding the implementation of
      peripheral iridectomy. Early postoperative complications in 10 patients: 3x
      pupillary block, 1x fibrin reaction in anterior chamber, 1 curled strip of
      anterior chamber in 1st postoperative day, 3x coiled plate with localized corneal
      oedema, 1 residual membrane size 2 x 2 mm Descemet slats off the optical axis.
      Late postoperative complications were recorded in a total of 7 patients. 4
      occurred secondary glaucoma and 2 corneal edema localized outside the optical
      zone. Once there was a bridging of traction plates. Visual acuity in
      uncomplicated patients were arranged within 21 days after surgery, patients with
      complications within 3 months. 1 times was made re DMEK rolled plates with the
      removal of the anterior chamber, 3 by 5 days to reposition scrolling border
      membranes by repeated big bubble technique. CONCLUSION: DMEK seems like a good
      option to remedy endothelium defects. About 70% of patients have fewer
      complications when used alone DMEK than cataract surgery combined with DMEK. For
      knowledgeable surgeon, starting with Descemet membrane transplantation, it is
      appropriate to separate transplants without combination with other procedures
      (cataract surgery, iriedktomy). Laser iridotomies before operation seems an
      appropriate procedure to avoid bleeding while surgery.

PMID- 22132645
TI  - [The use of confocal corneal microscopy in the Cogan microcystic dystrophy
      diagnosis and follow-up of the ultrastructural changes after phototherapeutic
      keratectomy].
AB  - Confocal microscopy represents modern, non-invasive, semi-contact examination
      method making possible to visualize separate corneal layers (from the endothel to
      the epithel) in high resolution. Phototherapeutic keratectomy (PTK) is a method
      using argon-fluoride laser with 193 nm wavelength to treat corneal surface
      diseases. AIM: To evaluate the use of confocal microscopy for epithelial basal
      membrane dystrophy diagnosis (Cogan microcystic dystrophy) and following corneal
      ultra-structural changes in vivo after PTK. MATERIAL AND METHODS: The group
      consisted of 14 eyes of 9 patients (6 men and 3 women) of average age 45.8 +/-
      14.4 years who underwent in the department in last two years phototherapeutic
      keratectomy for recurrent erosion in Cogan microcystic corneal dystrophy. For the
      diagnosis of this disease, the confocal corneal microscope (Confoscan 4, Nidek,
      probe x 40) was used. Computer controlled laser photoablation was in all patients
      performed; the average depth was 14.8 +/- 3.3 microm (Technolas 217, Bausch &
      Lomb). The follow-up visits were scheduled always day 5 and 12, and month 1, 3,
      6, and 12 after the PTK. The reactive processes in all corneal layers, the
      subepithelial inervation restoration velocity and recurrence of the primary
      disease detectable by means of the confocal corneal microscope were followed-up.
      RESULTS: Cogan microcystic dystrophy was diagnosed in all followed-up patients by
      means of confocal microscope according to the findings of the area thickening and
      corneal epithelium basal membrane irregularities. These patients were indicated
      to the PTK. After the treatment, the healing of the epithelial layer was finished
      as early as the fifth day. The subepithelial nervous plexus average regeneration
      period was 6.2 +/- 2.8 months. In all patients, the edema of the anterior stroma
      was found at the day 5. The beginning of the re-popularization of the anterior
      stroma by keratocytes from deeper layers we diagnosed, on average, at the day
      11.5 +/- 1.9 after the treatment and the following reduction after 5.1 +/- 1.4
      months. In the posterior stroma and in the endothel, no changes were found.
      During the follow-up period, in none of the followed-up patients, the recurrence
      of the primary disease was found. CONCLUSION: The confocal microscopy may be
      recommended for superficial corneal dystrophies quality and accurate diagnosis
      and to follow up changes after phototherapeutic keratectomy as suitable treatment
      method of these diseases.

PMID- 22132646
TI  - [Lasik after corneal ulcer].
AB  - Our case report presents successful treatment of corneal ulcer caused by the most
      common pathogen of infectious keratitis--Pseudomonas aeruginosa. Treatment was
      followed by LASIK as a final refractive error solution. 20 year old patient
      (contact lens wearer) was admitted for acute infectious corneal ulcer in her left
      eye. Her visual acuity was 0.5 partial with full correction. Intensive local
      treatment with Tobramycin, Ofloxacin and Scopolamin was started. After healing of
      infectious focuses, local steroids (Fluorometholonin acetas) were used to clear
      residual stromal haze. Refractive error was corrected after stabilisation using
      LASIK. Longstanding visual acuity is thanks to the early and intensive therapy
      1.0 bilaterally.

PMID- 22132647
TI  - [Eye and inflammatory bowel diseases].
AB  - AIM: To point out the wide range of ocular features of inflammatory bowel
      diseases (IBD), focusing on uveitis. METHODS: A retrospective study. RESULTS: In
      the Centre for diagnosis and therapy of uveitis of our Ophthalmology Department,
      we have in years 2003-2010 followed in total 18 patients with intraocular
      inflammation associated with IBD: anterior uveitis (14), vasculitis (1),
      panuveitis (1), infectious uveitis as a secondary complication of systemic
      immunosuppressive therapy (2). The most often diagnosis was mild to moderate
      recurrent acute anterior uveitis. We have noticed more severe course of uveitis
      in patients with the HLA B27 positivity. Part of this paper consists of an
      overview of other ocular manifestations of IBD and current available
      therapeutical strategies. CONCLUSION: Ocular manifestations of IBD can be a
      valuable signal of the activity of the primary disease. The knowledge of the
      ocular manifestations of these systemic diseases and of possible complications is
      required for successful interdisciplinary care of patients with IBD. While local
      treatment is fully in hands of an ophthalmologist, the form and extent of the
      systemic treatment is necessary to coordinate with gastroenterologists.

PMID- 22132648
TI  - [The reconstruction of conjunctival socket after enucleation of the eye in post-
      two possibilities of surgical solution].
AB  - The aim of article was to describe two possibilities of reconstruction of
      contracted and deformed conjunctival socket at the patient undergoing enucleation
      of the eye many years ago. METHOD: The free full-thickness mucosa graft was used
      in local anaesthetic for reconstruction conjunctival socket at the first patient.
      The amnion membrane was used in the second case with correction of ectropion of
      lower eyelid. RESULTS: The good cosmetic and stabile effect was obtained in both
      cases.

PMID- 22132649
TI  - [Orbital ontogen dermoid cyst].
AB  - In the paper is described the very rare orbital dermoid cyst in lacrimal sac
      region containing ectopic dental elements. There was an uneventful clinical
      picture after the first operation, but a recurrence of the cyst with the presence
      of teeth in lacrimal region of the down eyelid has occurred four years after the
      first operation. After exstirpation of entire cyst contents has been achieved the
      favourable cosmetic and functional result.

PMID- 22132650
TI  - [Lyell's disease--a case report].
AB  - Lyell's disease is a rare, life-threatening, acute dermatologic disease. The
      mucous membranes are also often involved. Nearly all cases are induced by
      medications. There is currently no specific treatment and interdisciplinary
      cooperation is very important. The authors present a case report of a 15 year old
      boy with the ocular manifestations of Lyell's disease, triggered by lamotrigine.
      He was admitted to the burn unit with involvement of 85% of his body surface
      area. Ocular manifestations documented during hospitalization were classified as
      mild (lid edema, conjunctival injection) and later severe (multiple
      symblepharons). The patient was treated with antibiotic eyedrops/ointment,
      corticosteroid eyedrops/ointment, topical lubricants and a glass rod was used to
      lyse the symblepharons. At 23 months of follow-up our patient had a symblepharon
      which blocked the superior and inferior punctum in both eyes, without
      conjunctival fornix foreshortening or corneal abnormalities, minimal ocular
      discomfort.

PMID- 22132651
TI  - [Vaccination against viral hepatitis A and B in adults aged over 40 years-
      antibody persistence and immune memory].
AB  - STUDY OBJECTIVE: Primary vaccination with combined vaccine against viral
      hepatitis A (VHA) and viral hepatitis B (VHB) induces higher anti-hepatitis B
      surface (anti-HBs) antibody responses and similar anti-hepatitis A virus (anti
      HAV) antibody responses in adults aged over 40 years in comparison with
      concomitant monovalent vaccines against VHA and VHB. Th e objectives were to
      assess, in a clinical study, persistence of anti-HAV and anti-HBs antibodies in
      adults aged over 40 years four years after primary VHA/VHB vaccination and
      antibody response following a booster dose of the vaccine. MATERIAL AND METHODS:
      Five hundred and ninety-six subjects aged > 40 years were vaccinated with three
      doses of the combined VHA/VHB vaccine at Months 0, 1, 6 (HAB group) or with
      concomitant VHA and VHB vaccines at Months 0, 6 and 0, 1, 6 (ENG+HAV and
      HBVX+VAQ, respectively). Blood samples were collected one month following primary
      vaccination (Month 7) and then at one-year intervals for four years after the
      booster dose with the same vaccine as used for the primary vaccination. The anti
      HBs and anti-HAV antibody levels were determined prior to the booster dose and at
      days 14 and 30 after the booster dose. RESULTS: At Month 7, > 97% of study
      subjects were seropositive for anti-HAV antibodies in all groups analyzed. Four
      years after primary vaccination, anti-HAV antibody seropositivity persisted in >
      93% of study subjects, increasing to > 99% after the booster dose. At Month 7,
      the highest proportion of study subjects with anti-HBs antibody levels > or = 10
      mIU/ml was found in the HAB group (91.7% versus 79.7% in the ENG+HAV group versus
      71.0% in the HBVX+VAQ group). Four years after vaccination, anti-HBs antibody
      levels of 10 mIU/ml persisted in 57.1% of the HAB study subjects in comparison
      with 40.1% and 26.6% of the study subjects in the ENG+HAV and HBVX+VAQ groups,
      respectively. One month after the booster dose, anti-HBs antibody levels
      increased and antibody levels > or = 10 mIU/ml was achived in 95.2% of study
      subjects in the HAB group, 90.5% in the ENG+HAV group and 85.3% in the HBVX+VAQ
      group. CONCLUSION: In the adults aged over 40 years, an adequate anti-HAV
      antibody response persisted for at least four years after vaccination and was
      higher and more sustained in those who received the combined HAB vaccine. A
      strong antibody response to the booster dose indicative ofthe presence of immune
      memory was seen in all study groups.

PMID- 22132652
TI  - [Prevention of tick-borne meningoencephalitis--summary report].
AB  - Tick-borne meningoencephalitis is a zoonosis that shows an upward trend. The
      causative agent is an RNA virus of the family Flaviviridae whose vector in
      Central Europe is the castor bean tick (Ixodes ricinus). The infection is most
      often transmitted via tick bite or, less commonly, by the alimentary route,
      through the consumption of unpasteurized milk of infected animals. Preventive
      measures consist in personal protection from ticks, exceptionally in blanket
      treatment with contact insecticides, in preventing consumption of unpasteurized
      milk and dairy products from areas with a high incidence of tick-borne
      encephalitis, and particularly in vaccination of the susceptible population.

PMID- 22132653
TI  - [The use of IgG antibody avidity assays in the diagnosis of cytomegalovirus
      infection].
AB  - Human cytomegalovirus (CMV) is the most common cause of congenital infection.
      Primary CMV infection can lead to severe disease and complications in patients
      immunocompromised as a result of disease or therapy. IgG antibody avidity assays
      make it possible to differentiate between primary infection and reactivation of
      latent infection or reinfection. The study objective was to determine CMV IgG
      avidity by enzyme-linked immunosorbent assay (ELISA) with denaturation of IgG
      antibody binding to the antigen and by chemiluminiscent microparticle immunoassay
      (CMIA) on an Abbott Architect analyzer. Both methods yielded comparable CMV IgG
      avidity results. In some cases, the Abbott test was superior in reflecting IgG
      antibody maturation during primary infection to microplate ELISA using antigen
      antibody complex dissociation by a denaturing agent.

PMID- 22132654
TI  - [Amoebae of the genus Acanthamoeba--causative agents of human infections].
AB  - Amoebae of the genus Acanthamoeba Volkonsky, 1931 are ubiquitous, amphizoic
      organisms with a cosmopolitan distribution. Pathogenic strains are the causative
      agents of a difficult to treat disease, granulomatous amoebic encephalitis (GAE),
      and skin infections in immunocompromised individuals, and of a painful corneal
      disease--amoebic keratitis (AK) in immunocompetent individuals. The major portals
      of entry are the nasopharyngeal mucosa, pulmonary parenchyma, skin lesions (GAE,
      skin infections), eyes in contact lenses wearers with a history of improper
      contact lens wear and care, or corneal trauma (AK). Symptoms of the diseases are
      non-specific and variable which alongside with the lack of awareness among health
      care professionals often hamper early diagnosis. While treatment options for GAE
      and skin infections are limited and poorly effective, various antifungals and
      antimicrobials have proved beneficial in AK, although the therapy is often
      complicated and long.

PMID- 22132655
TI  - Controlling your health care costs: transparency.

PMID- 22132656
TI  - Dental management of the head & neck cancer patient treated with radiation
      therapy.

PMID- 22132657
TI  - Xerostomia: diagnosis and management in dental practice.
AB  - Xerostomia is a subjective sensation of oral dryness. It is caused by many
      factors, among them, hypo/hyper salivation. This article covers the etiology,
      local and systemic factors related to dryness of the mouth, its diagnosis, and
      clinical and at-home management of the syndrome. It also reviews the role of
      dental hygiene intervention to improve and promote the patient's quality of life.
      It is hoped this review will help dental health care providers better respond to
      patients afflicted with xerostomia.

PMID- 22132658
TI  - Digital imaging in dentistry.
AB  - Information technology is vital to operations, marketing, accounting, finance and
      administration. One of the most exciting and quickly evolving technologies in the
      modern dental office is digital applications. The dentist is often the business
      manager, information technology officer and strategic planning chief for his
      small business. The information systems triangle applies directly to this
      critical manager supported by properly trained ancillary staff and good
      equipment. With emerging technology driving all medical disciplines and the rapid
      pace at which it emerges, it is vital for the contemporary practitioner to keep
      abreast of the newest information technology developments. This article compares
      the strategic and operational advantages of digital applications, specifically
      imaging. The focus of this paper will be on digital radiography (DR), 3D
      computerized tomography, digital photography and digitally-driven CAD/CAM to what
      are now considered obsolescing modalities and contemplates what may arrive in the
      future. It is the purpose of this essay to succinctly evaluate the decisions
      involved in the role, application and implications of employing this tool in the
      dental environment

PMID- 22132659
TI  - Kaiser Permanente's performance improvement system, part 3: multisite
      improvements in care for patients with sepsis.
AB  - BACKGROUND: In 2008, Kaiser Permanente Northern California implemented an
      initiative to improve sepsis care. Early detection and expedited implementation
      of sepsis treatment bundles that include early goal-directed therapy (EGDT) for
      patients with severe sepsis were implemented. METHODS: In a top-down, bottom-up
      approach to performance improvement, teams at 21 medical centers independently
      decided how to implement treatment bundles, using a "playbook" developed by rapid
      cycle pilot testing at two sites and endorsed by a sepsis steering committee of
      regional and medical center clinical leaders. The playbook contained treatment
      algorithms, standardized order sets and flow charts, best practice alerts, and
      chart abstraction tools. Regional mentors and improvement advisers within the
      medical centers supported team-building and rapid implementation. Timely and
      actionable data allowed ongoing identification of improvement opportunities. A
      consistent approach to performance improvement propelled local rapid improvement
      cycles and joint problem solving across facilities. RESULTS: The number of sepsis
      diagnoses per 1,000 admissions increased from a baseline value of 35.7 in July
      2009 to 119.4 in May 2011. The percent of admitted patients who have blood
      cultures drawn who also have a serum lactate level drawn increased from a
      baseline of 27% to 97% in May 2011. The percent of patients receiving EGDT who
      had a second and lower lactate level within six hours increased from 52% at
      baseline to 92% in May 2011. CONCLUSION: Twenty-one cross-functional frontline
      teams redesigned processes of care to provide regionally standardized, evidence
      based treatment algorithms for sepsis, substantially increasing the
      identification and risk stratification of patients with suspected sepsis and the
      provision of a sepsis care bundle that included EGDT.

PMID- 22132660
TI  - Patient-reported adverse events: what are we waiting for?

PMID- 22132661
TI  - Reporting of sentinel events in Swedish hospitals: a comparison of severe adverse
      events reported by patients and providers.
AB  - BACKGROUND: Mandatory and voluntary reporting of adverse events is common in
      health care organizations but a more accurate understanding of the extent of
      patient injury may be obtained if additional sources are used. Patients in Sweden
      may file a claim for economic compensation from the national insurance system if
      they believe they have sustained an injury. The extent and pattern of reporting
      of serious adverse events in a mandatory national reporting system was compared
      with the reporting of adverse events on the basis of patient claims. METHODS:
      Regional sentinel event reports were compared with malpractice claims data
      between 1996 and 2003. A sample consisting of 113 patients with deaths or serious
      injuries was selected from the malpractice claims data source. The medical
      records of these patients were reviewed by three chief medical officers. RESULTS:
      Of the deaths or injuries associated with the 113 patients-25 deaths, 37 with
      more than 30% disability, and 51 with 16/o-30% disability-23 (20%) had been
      reported by chief medical officers to the National Board of Health and Welfare as
      sentinel events. Most adverse events were found in orthopedic surgery, and
      orthopedic injuries had more serious consequences. None of the patient injuries
      caused by infections were reported as sentinel events. Individual errors were
      more frequent in cases reported as sentinel events. CONCLUSIONS: Adverse events
      causing severe harm are underreported to a great extent in Sweden despite the
      existence of a mandatory reporting system; physicians often consider them to be
      complications. Health care organizations should consider using a portfolio of
      tools-including incident reporting, medical record review, and analysis of
      patient claims-to gain a comprehensive picture of adverse events.

PMID- 22132662
TI  - Patients' identification and reporting of unsafe events at six hospitals in
      Japan.
AB  - BACKGROUND: Hospitals and other health care organizations have increasingly
      recognized the need to engage patients as participants in patient safety. A study
      was conducted to compare patients' and health care staff's identification and
      reporting of such events. METHODS: A questionnaire was administered at six
      hospitals in Japan to outpatients and inpatients from November 2004 through
      February 2007. Patients were asked to respond to questions about experiences of
      possibly unsafe events. Patients experiencing such events were then asked about
      the events and whether they had reported their experience to health care staff. A
      specialist panel classified reported events as "uneasy-dissatisfying" or
      "unsafe." RESULTS: The response rates of outpatients and inpatients were 85.4%
      (1,506/1,764) and 54.3% (1,738/3,198), respectively. Among the respondents (> or
      = 20 years of age), 125 (8.7%) of the outpatients and 185 (10.9%) of the
      inpatients experienced uneasy-dissatisfying or unsafe events; 35 (2.4%) of the
      outpatients and 67 (4.0%) of the inpatients experienced unsafe events, the
      percent increasing with hospital stay. Only 38 (30.4%) of the outpatients and 62
      (33.5%) of the inpatients reported the unsafe events to health care staff
      CONCLUSION: Only 17.1% of unsafe events reported by inpatients were identified by
      the in-house reporting systems of adverse events and near misses. For the uneasy
      dissatisfying or unsafe events that patients did not think necessary to report,
      the patients often felt they were self-evident or easily identifiable by health
      care staff, had difficulty evaluating the event, did not expect their report to
      bring any improvement, or even felt that reporting it would create some
      disadvantage in their medical treatment. Patient reporting programs and in-house
      reporting systems, among other detection methods, should be regarded as
      complementary sources of information.

PMID- 22132663
TI  - Improving safety culture results in Rhode Island ICUs: lessons learned from the
      development of action-oriented plans.
AB  - BACKGROUND: The Rhode Island (RI) Intensive Care Unit (ICU) Collaborative was
      designed to improve patient safety and clinical outcomes in adult ICUs through a
      unit-based patient safety program and evidenced-based practices. Few studies have
      shown how to draw on a strong safety culture to improve clinical outcomes. A
      study was conducted to (1) examine the impact of a Safety Attitudes Questionnaire
      Action Plan (SAQAP) on the 2008 Safety Attitudes Questionnaire (SAQ) and (2)
      determine the impact of an SAQAP on ICU central line-associated blood stream
      infections (CLABSIs) and ventilator-associated pneumonia (VAP) rates. METHODS:
      The SAQ was administered at 23 ICUs in 11 hospitals in fall 2007 and 2008. Units
      were surveyed as to whether they completed an SAQAP on the basis of 2007 SAQ
      results. Annual rates of infection were submitted as unadjusted monthly CLABSI
      infections per 1,000 line days and VAP infections per 1,000 ventilator days for
      2007 and 2008. RESULTS: SAQAPs were completed on 9 (39%) of the 23 units. Units
      that developed SAQAPs demonstrated higher improvement rates in all domains of the
      SAQ except working conditions. Improvements were close to statistical
      significance for teamwork climate (+18.4% in SAQAP units versus -6.4%, p = .07)
      and job satisfaction (+25.9% increase in SAQAP units versus +7.3%, p = .07).
      Units with SAQAPs decreased the CLABSI rates by 10.2% in 2008 compared with 2007,
      while those without SAQAP had a 2.2% decrease in rates (p = .59). Similarly, VAP
      rates decreased by 15.2% in SAQAP units, while VAP rates increased by 4.8% in
      units without SAQAP (p = .39). CONCLUSIONS: Teams that developed SAQAPs improved
      their unit culture and clinical outcomes. An active, targeted intervention in
      culture can translate into improved outcomes for patients.

PMID- 22132664
TI  - Simulated pediatric resuscitation use for personal protective equipment adherence
      measurement and training during the 2009 influenza (H1N1) pandemic.
AB  - BACKGROUND: Previous experience with simulated pediatric cardiac arrests (that
      is, mock codes) suggests frequent deviation from American Heart Association (AHA)
      basic and advanced life support algorithms. During highly infectious outbreaks,
      acute resuscitation scenarios may also increase the risk of insufficient personal
      protective equipment (PPE) use by health care workers (HCWs). Simulation was used
      as an educational tool to measure adherence with PPE use and pediatric
      resuscitation guidelines during simulated cardiopulmonary arrests of 2009
      influenza A patients. METHODS: A retrospective, observational study was performed
      of 84 HCWs participating in 11 in situ simulations in June 2009. Assessment
      included (1) PPE adherence, (2) confidence in PPE use, (3) elapsed time to
      specific resuscitation maneuvers, and (4) deviation from AHA guidelines. RESULTS:
      Observed adherence with PPE use was 61% for eye shields, 81% for filtering
      facepiece respirators or powered air-purifying respirators, and 87% for
      gown/gloves. Use of a "gatekeeper" to control access and facilitate donning of
      PPE was associated with 100% adherence with gown and respirator precautions and
      improved respirator adherence. All simulations showed deviation from pediatric
      basic life support protocols. The median time to bag-valve-mask ventilation
      improved from 4.3 to 2.7 minutes with a gatekeeper present. Rapid isolation carts
      appeared to improve access to necessary PPE. Confidence in PPE use improved from
      64% to 85% after the mock code and structured debriefing. CONCLUSIONS: Large gaps
      exist in the use of PPE and self-protective behaviors, as well as adherence to
      resuscitation guidelines, during simulated resuscitation events. Intervention
      opportunities include use of rapid isolation measures, use of gatekeepers,
      reinforcement of first responder roles, and further simulation training with PPE.

PMID- 22132666
TI  - Closing doors, saving services.
AB  - After ending inpatient care, a hospital recommits to its community.

PMID- 22132665
TI  - Screen savers as an adjunct to medical education on patient safety.
AB  - BACKGROUND: Many health care organizations use screen savers on the computer
      terminals in patient care areas to provide educational messages and announcements
      for staff and patients. The effectiveness of screen savers for educating medical
      students about patient safety was investigated. METHODS: Screen savers were
      designed to teach 10 patient safety concepts based on The Joint Commission's
      National Patient Safety Goals. Two similar academic medical centers, one which
      already had a screen-saver system and one which did not, were selected for the
      study. The third-year medical students rotating at the intervention medical
      center were exposed to the patient safety screen savers throughout their three-to
      four-week rotations, while students rotating at the control site were not. All
      students were given a multiple choice test of patient safety concepts before the
      start of their first rotation and again after its completion. RESULTS: The median
      pretest score for the intervention and control groups was 45% (interquartile
      range [IQR], 40%-55%) and 40% (IQR, 35%-50%), respectively. The median
      improvement in test scores was 15% for both the 11 students in the control group
      (IQR, 10%-25%) and the 27 students in the intervention group (IQR: 10%-20%)-both
      at p < .001. CONCLUSIONS: Students showed some improvement in patient safety
      knowledge after completing their first clinical rotation, regardless of screen
      saver exposure. This improvement was likely due to general exposure to
      appropriate safety practices as exhibited by housestaff and faculty. Despite the
      widespread use of screen savers, no evidence was provided that they are an
      effective method for teaching patient safety concepts to medical students.
      Further research is needed to determine whether they are effective for medical
      education in other situations.

PMID- 22132667
TI  - Commanding safety: how the VA drives systemwide error prevention.
AB  - Using presurgery briefings and root cause analysis, Veterans Affairs hospitals
      make impressive safety gains.

PMID- 22132668
TI  - Closing the leadership gap: Boards drive the CEO succession process. Is your
      transition plan ready?
AB  - CEO succession planning is a board function. Is your plan current and ready to
      deploy?

PMID- 22132670
TI  - The ICD-10 to-do list. Brace yourself: the new coding system affects physicians
      and financials.
AB  - The transition to a new clinical coding system will be a multiphase endeavor,
      ideally led by the CFO.

PMID- 22132669
TI  - Integrity in action. Boards' compliance oversight sets the standard for ethical,
      legal practices.
AB  - The board's compliance oversight responsibility starts with engaged, educated
      trustees. Learn the basics here.

PMID- 22132671
TI  - Community health needs assessment.

PMID- 22132672
TI  - Governance at a crossroads. Trustees' role in the future of health care.

PMID- 22132673
TI  - First, do no harm. Mandatory influenza vaccination for health care workers is a
      matter of patient safety.
AB  - A commitment to patient safety drove a system's decision to require influenza
      vaccination of employees.

PMID- 22132674
TI  - Clearing the pathway. Health care leaders are working to bring gender parity to
      the C-suite and board room.
AB  - C-suites and boardrooms are missing a critical element: female leadership.

PMID- 22132675
TI  - Quality turnaround.
AB  - A quality "dream team" helps turn around a hospital's performance.

PMID- 22132676
TI  - Intensivists on the rise. Proven safety gains mean these physicians are becoming
      preferred ICU providers.
AB  - Larger hospitals are more likely to use intensivists to provide ICU care.

PMID- 22132677
TI  - Non-enteral therapy for hypertension in the inpatient setting.
AB  - Chronic hypertension requiring treatment with regularly administered oral
      medications is the most common cardiovascular disease among adults. When patients
      with hypertension suffer an illness which requires hospitalization and precludes
      normal oral drug intake, blood pressure may rise sufficiently to require
      alternative treatments. Consequences of the acute illnesses themselves and their
      treatments may also elevate blood pressure and further complicate
      antihypertensive management. The optimal medical regimen to control blood
      pressure under these circumstances depends upon a number of variables, including
      co-morbid conditions, concurrently administered drugs, and the overall clinical
      stability of the patient. This paper reviews issues related to hypertension in
      the hospitalized patient unable to take oral medications and summarizes
      antihypertensive treatment options based on clinical and pharmacological
      considerations.

PMID- 22132678
TI  - Doctor, please don't send me home like this!

PMID- 22132679
TI  - Reflections on a squashed resolution.

PMID- 22132680
TI  - Greater Jackson Chamber Partnership announces Mississippi Healthcare Corridor.

PMID- 22132681
TI  - Who will care for the newly insured under health reform?

PMID- 22132683
TI  - Successful combination therapy with dapsone and cyclosporine for erythema
      elevatum diutinum with unusual appearance.

PMID- 22132684
TI  - Recombinant and natural human interferons: analysis of the incidence and clinical
      impact of neutralizing antibodies.
AB  - This review summarizes and analyzes the clinical outcomes following treatment of
      a wide range of diseases with recombinant interferons (r-IFNs) and/or natural
      interferons (n-IFNs). The investigation focuses on the frequency of neutralizing
      antibodies (NABs) directed against IFN, which are formed during treatment and
      their clinical impact. r-IFNs (alpha-2a, alpha-2b, beta-1a, and beta-1b) induced
      seroconversion with generation of NABs in 17.2% of patients studied. The highest
      incidence of NABs occurred in macular degeneration (61.4%) with the lowest in
      multiple sclerosis (14.7%). The incidence of antibodies induced against n-IFNs
      was very low (<0.2%) and was significantly less than that seen for r-IFNs
      (P<0.0001). Overall, the fraction of relapsed and refractory patients is
      statistically greater in NAB positive patients compared to NAB negative patients
      (<0.0001), whereas the percentage of responding patients is higher in the NAB
      negative cohort (P<0.001). Finally, we also analyzed relapsed and refractory NAB
      positive patients who switched treatment to n-IFN, such as leukocyte derived
      Alferon N Injection(r) (alpha-n3) or Wellferon(r) (alpha-n1). Overall, in 33/40
      (82%) of these relapsed or refractory patients, switching to n-IFNs restored the
      clinical response. This result is consistent with serology studies showing that
      the NABs directed against r-IFNs do not effectively cross-react with n-IFNs.

PMID- 22132685
TI  - The association between perceived sweetness intensity and dietary intake in young
      adults.
AB  - Individual differences in taste perception may influence dietary habits,
      nutritional status, and ultimately nutrition-related chronic disease risk.
      Individual differences in sweetness intensity perception and the relationship
      between perceived sweetness intensity, food behaviors, and dietary intake was
      investigated in 85 adults. Subjects (body mass index [BMI]= 21 +/- 3, 21 +/- 4 y)
      completed a food and diet questionnaire, food variety survey, 2 24-h food
      records, and a perceived sweetness intensity measurement using the general
      labeled magnitude scale (gLMS). There was interindividual variation in perceived
      sweetness intensity (0 to 34 gLMS units, mean 10 +/- 7). One-way analysis of
      variance (ANOVA) revealed no difference between perceived sweetness intensity and
      degree of importance placed on not adding sugar to tea or coffee (P = 0.2) and
      the degree of importance placed on avoiding sugar-sweetened or fizzy drinks (P =
      1.0). Independent t-test analysis revealed no significant association between
      perceived sweetness intensity and the food variety measure for sugar and
      confectionary intake (P = 0.6) and selected fruit and vegetable intake (P = 0.1
      to 0.9). One-way ANOVA also demonstrated no difference between tertiles of
      sweetness intensity and BMI (P = 0.1), age (P = 0.3), and food variety score (P =
      0.5). No correlation was observed with regards to perceived sweetness intensity
      and mean total energy (kJ) intake (r = 0.05, P = 0.7), percent energy from total
      fat, saturated fat, protein, carbohydrate, and grams of fiber (r =-0.1 to 0.1, P
      = 0.2 to 0.8) and also for intake of the micronutrients: folate, magnesium,
      calcium, iron, and zinc (r = 0.1 to 0.2, P = 0.1 to 0.4). Only modest
      correlations were observed between sodium (r = 0.3, P < 0.05), vitamin C (r =
      0.3, P < 0.05), and potassium (r = 0.2, P < 0.0) intake and perceived sweetness
      intensity. Overall, perceived sweetness intensity does not appear to play a role
      in food behaviors relating to sugar consumption and dietary intake in adults.

PMID- 22132686
TI  - Reactivity and stability of dinuclear Pd(I) complexes: studies on the active
      catalytic species, insights into precatalyst activation and deactivation, and
      application in highly selective cross-coupling reactions.
AB  - The catalysis derived from the dinuclear Pd(I)-Pd(I) complex, {[PtBu(3)]PdBr}(2),
      has been studied with experimental, computational, and spectroscopic techniques.
      Experimental selectivity studies were performed, and the reactivity was
      subsequently investigated with density functional theory (B3LYP-D and M06L) to
      deduce information on the likely active catalytic species. The reactivity with
      aryl chlorides and bromides was found to be inconsistent with direct catalytic
      involvement of the Pd(I) dimer but consistent with mononuclear Pd(0) catalysis.
      Computational studies suggest that precatalyst transformation to the active
      catalytic species does not proceed via a direct disproportionation mechanism; a
      reductive pathway is the most likely scenario instead. Through (31)P NMR
      investigations it was identified that the combination of ArB(OH)(2), KF, and
      water triggers the conversion of the precatalyst to Pd(PtBu(3))(2) and, most
      likely, Pd-black as a competing side process, explaining the incomplete
      conversions of aryl chlorides in Suzuki cross-coupling reactions under Pd(I)
      dimer conditions. New applications in highly regio- and chemoselective
      transformations in short reaction times at room temperature are also
      demonstrated.

PMID- 22132687
TI  - Survey of CAM interest, self-care, and satisfaction with health care for type 2
      diabetes at group health cooperative.
AB  - BACKGROUND: Very little research has explored the factors that influence interest
      in complementary and alternative medicine (CAM) treatments. We surveyed persons
      with sub-optimally controlled type 2 diabetes to evaluate potential relationships
      between interest in complementary and alternative medicine (CAM) treatments,
      current self-care practices, motivation to improve self-care practices and
      satisfaction with current health care for diabetes. METHODS: 321 patients from a
      large integrated healthcare system with type 2 diabetes, who were not using
      insulin and had hemoglobin A1c values between 7.5-9.5%, were telephoned between
      2009-2010 and asked about their self-care behaviors, motivation to change,
      satisfaction with current health care and interest in trying naturopathic (ND)
      care for their diabetes. Responses from patients most interested in trying ND
      care were compared with those from patients with less interest. RESULTS: 219
      (68.5%) patients completed the survey. Nearly half (48%) stated they would be
      very likely to try ND care for their diabetes if covered by their insurance.
      Interest in trying ND care was not related to patient demographics, health
      history, clinical status, or self-care behaviors. Patients with greater interest
      in trying ND care rated their current healthcare as less effective for
      controlling their blood sugar (mean response 5.9 +/- 1.9 vs. 6.6 +/- 1.5, p =
      0.003), and were more determined to succeed in self-care (p = 0.007). Current CAM
      use for diabetes was also greater in ND interested patients. CONCLUSIONS:
      Patients with sub-optimally controlled type 2 diabetes expressed a high level of
      interest in trying ND care. Those patients with the greatest interest were less
      satisfied with their diabetes care, more motivated to engage in self-care, and
      more likely to use other CAM therapies for their diabetes.

PMID- 22132688
TI  - Dystrophin deficiency exacerbates skeletal muscle pathology in dysferlin-null
      mice.
AB  - BACKGROUND: Mutations in the genes coding for either dystrophin or dysferlin
      cause distinct forms of muscular dystrophy. Dystrophin links the cytoskeleton to
      the sarcolemma through direct interaction with beta-dystroglycan. This link
      extends to the extracellular matrix by beta-dystroglycan's interaction with alpha
      dystroglycan, which binds extracellular matrix proteins, including laminin
      alpha2, agrin and perlecan, that possess laminin globular domains. The absence of
      dystrophin disrupts this link, leading to compromised muscle sarcolemmal
      integrity. Dysferlin, on the other hand, plays an important role in the Ca2+
      dependent membrane repair of damaged sarcolemma in skeletal muscle. Because
      dysferlin and dystrophin play different roles in maintaining muscle cell
      integrity, we hypothesized that disrupting sarcolemmal integrity with dystrophin
      deficiency would exacerbate the pathology in dysferlin-null mice and allow
      further characterization of the role of dysferlin in skeletal muscle. METHODS: To
      test our hypothesis, we generated dystrophin/dysferlin double-knockout (DKO) mice
      by breeding mdx mice with dysferlin-null mice and analyzed the effects of a
      combined deficiency of dysferlin and dystrophin on muscle pathology and
      sarcolemmal integrity. RESULTS: The DKO mice exhibited more severe muscle
      pathology than either mdx mice or dysferlin-null mice, and, importantly, the
      onset of the muscle pathology occurred much earlier than it did in dysferlin
      deficient mice. The DKO mice showed muscle pathology of various skeletal muscles,
      including the mandible muscles, as well as a greater number of regenerating
      muscle fibers, higher serum creatine kinase levels and elevated Evans blue dye
      uptake into skeletal muscles. Lengthening contractions caused similar force
      deficits, regardless of dysferlin expression. However, the rate of force recovery
      within 45 minutes following lengthening contractions was hampered in DKO muscles
      compared to mdx muscles or dysferlin-null muscles, suggesting that dysferlin is
      required for the initial recovery from lengthening contraction-induced muscle
      injury of the dystrophin-glycoprotein complex-compromised muscles. CONCLUSIONS:
      The results of our study suggest that dysferlin-mediated membrane repair helps to
      limit the dystrophic changes in dystrophin-deficient skeletal muscle. Dystrophin
      deficiency unmasks the function of dysferlin in membrane repair during
      lengthening contractions. Dystrophin/dysferlin-deficient mice provide a very
      useful model with which to evaluate the effectiveness of therapies designed to
      treat dysferlin deficiency.

PMID- 22132689
TI  - Morphological versus functional photoreceptor viability of retinal pigment
      epithelium tears.

PMID- 22132690
TI  - A novel Internet-based blended learning programme providing core competency in
      clinical research.
AB  - RATIONALE, AIMS AND OBJECTIVES: We developed a novel Internet-based blended
      learning programme that allows busy health care professionals to attain core
      competency in clinical research. This study details the educational strategies
      and learning outcomes of the programme. METHOD: This study was conducted at Kyoto
      University and seven satellite campuses from September 2009 to March 2010. A
      total of 176 health care professionals who had never attempted to attain core
      competency in clinical research were enrolled. The participants were supplied
      with a novel programme comprising the following four strategies: online live
      lectures at seven satellite campuses, short examinations after each lecture, an
      Internet-based feedback system and an end-of-course examination. We assessed the
      proportion of attendance at the lectures as the main outcome. In addition, we
      evaluated interaction via the feedback system and scores for end-of-course
      examination. RESULTS: Of the 176 participants, 134 (76%) reported working more
      than 40 hours per week. The mean proportion of attendance over all 23 lectures
      was 82%. A total of 156 (89%) participants attended more than 60% of all lectures
      and were eligible for the end-of-course examination. A total of the participants
      accessed the feedback system 3564 times and asked 284 questions. No statistically
      significant differences were noted in the end-of-course scores among medical
      doctors, pharmacists, registered nurses and other occupations. CONCLUSIONS: We
      developed an Internet-based blended learning programme providing core competency
      in clinical research. Most busy health care professionals completed the programme
      successfully. In addition, the participants could attain the core competency
      effectively, regardless of their occupation.

PMID- 22132691
TI  - The objective assessment of cough frequency: accuracy of the LR102 device.
AB  - BACKGROUND: The measurement of cough frequency is problematic and most often
      based on subjective assessment. The aim of the study was to assess the accuracy
      of the automatic identification of cough episodes by LR102, a cough frequency
      meter based on electromyography and audio sensors. METHODS: Ten adult patients
      complaining of cough were recruited in primary care and hospital settings.
      Participants were asked to wear LR102 for 4 consecutive hours during which they
      were also filmed. RESULTS: Measures of cough frequency by LR102 and manual
      counting were closely correlated (r = 0.87 for number of cough episodes per hour;
      r = 0.89 for number of single coughs per hour) but LR102 overestimated cough
      frequency. Bland-Altman plots indicate that differences between the two
      measurements were not influenced by cough frequency. CONCLUSIONS: LR102 offers a
      useful estimate of cough frequency in adults in their own environment, while
      significantly reducing the time required for analysis.

PMID- 22132692
TI  - Chemical constituents, antioxidant and antimocrobial activity of essential oil of
      Pogostemon paniculatus (Willd.).
AB  - The essential oil extracted from the leaves of Pogostemon paniculatus (Willd.)
      Benth. (Lamiaceae), was analysed by gas chromatography-mass spectrometry (GC-MS).
      Nineteen compounds constituting 85.36% of the total oil were identified in the
      oil. Patchouli alcohol (30.65%), alpha-guaiene (10.67%), beta-guaiene (9.09%),
      caryophyllene (8.64%), eicosene (5.27%) were the major constituents present. The
      essential oil was analysed for antimicrobial activity by disc diffusion assay and
      minimum inhibition concentration against six bacteria and three fungi. Results
      showed inhibitory activity against some of the tested microorganisms. The
      essential oil was also tested for the DPPH free-radical scavenging activity and
      had an inhibitory concentration (IC(50)) value of 18.5 ug mL(-1).

PMID- 22132695
TI  - Reflective documentation: evidence of quality.
AB  - The 2011 American Nurses Credentialing Center accreditation criteria require
      thoughtful responses to a series of items designed to demonstrate the quality of
      work done by an accredited or approved provider. Information in this column
      reflects discussion about effective documentation during the Accreditation
      Preconference at the Professional Nurse Educators Group (PNEG) meeting in
      Baltimore on October 20, 2011.

PMID- 22132693
TI  - Post-transcriptional regulation of IL-6 production by Zc3h12a in fibroblast-like
      synovial cells.
AB  - OBJECTIVES: Zc3h12a is an RNA binding protein with a CCCH-type finger motif and
      is known to regulate mRNA metabolism. Previous reports suggest that Zc3h12a acts
      as a negative regulator of inflammatory processes because it is involved in the
      degradation of IL-6 mRNA. We investigate the effect of Zc3h12a on IL-6 production
      in fibroblast-like synovial cells (FLS) from rheumatoid arthritis (RA) patients.
      METHODS: The expression of Zc3h12a in FLS was determined by polymerase chain
      reaction. To knock down Zc3h12a expression in FLS, siRNA for Zc3h12a was
      transfected by the lipofection method. The supernatants were collected after
      siRNA transfection for the quantification of IL-6 production. The phosphorylation
      of the signal transducer and activator of transcription 3 (STAT3) was examined by
      Western blotting. Cell proliferation was analysed by the Cell Counting Kit-8
      assay after Zc3h12a knockdown. RESULTS: mRNA for Zc3h12a were demonstrated in FLS
      from RA patients. Zc3h12a transcripts were induced by LPS or IL-1beta in FLS. The
      production of IL-6 as well as its mRNA expression was significantly increased by
      the Zc3h12a knockdown. The Zc3h12a knockdown also induced the activation of
      STAT3, which the anti IL-6 receptor antibody inhibited. Proliferation of Zc3h12a
      knockdown FLS increased significantly in the presence of recombinant soluble IL-6
      receptor (sIL-6R). CONCLUSIONS: Our data suggest that Zc3h12a is a novel IL-6
      regulator in FLS, which may be involved in the progression of RA.

PMID- 22132696
TI  - Scripts: a tool for cognitive rehearsal.
AB  - Scripts, as a tool for cognitive rehearsal, can prepare staff and students to
      improve communication in critical patient or family encounters, situations
      requiring standardized communication for patient safety, and circumstances where
      interpersonal conflict exists.

PMID- 22132698
TI  - Three siblings with systemic lupus erythematosus.
AB  - We present the cases of three siblings with systemic lupus erythematosus (SLE).
      The diagnosis was made when the sisters were of age 21, 25 and 28 years. They
      shared some clinical features, including typical facial rash, photosensitivity
      and Raynaud's phenomenon, and tested positive for antinuclear antibodies.
      However, their symptoms and clinical courses varied. Human leukocyte antigen
      (HLA) typing revealed that DR4 and A2 were present in all three sisters, while
      HLA type A11, B35 and B54 were each found in two of the three sisters. The two
      elder sisters developed lupus glomerulonephritis 8 and 11 years after the onset
      of SLE. It is suggested that there are genes responsible for the onset of the
      disease and also unknown regulatory genes other than HLA result in different
      phenotypes.

PMID- 22132699
TI  - Discovering neurosurgery: new frontiers.
AB  - Over the centuries, discoveries of lands unknown, treasures lost and buried, and
      formulas to delineate physicochemical processes have led to advancements in our
      understanding of how the world is structured and governed. In science and
      medicine, discoveries are frequently made following deliberate periods of
      observation and experimentation to test hypotheses. However, in some instances,
      discoveries may arise either following a "eureka moment" that transcends rigorous
      scientific experimentation or following a serendipitous observation. In many
      instances, scientific discoveries will lead to new inventions that are aimed at
      improving the manner in which tasks or operations are performed. In this address,
      some of the key discoveries in science and medicine that have impacted
      significantly on the field of neurosurgery are described. Some of these include
      discoveries in neuroanatomy, anesthesiology, infectious diseases, antisepsis, and
      radiology. Discoveries in the field of molecular science, from the discovery of
      DNA to next-generation DNA sequencing, which have helped improve the diagnosis
      and prognosis of neurosurgical patients with conditions such as brain tumors, are
      also described. In the end, these discoveries have led us to new frontiers in the
      subspecialty practice of neurosurgery. Navigating our way through these new
      frontiers will undoubtedly lead to additional discoveries that are unimaginable
      at present but bound to improve the future care of neurosurgical patients.

PMID- 22132700
TI  - Characterization of the volatility of flavor compounds in alcoholic beverages
      through headspace solid-phase microextraction (HS-SPME) and mathematical
      modeling.
AB  - The volatility of flavor compounds (10 distinctive esters commonly found in
      alcoholic beverages) was characterized using headspace solid-phase
      microextraction (HS-SPME) analysis combined with mathematical modeling. The
      impacts of extrinsic factors (extraction time and temperature) and intrinsic
      parameters (ethanol content and concentration of these flavor compounds) were
      evaluated on their influences. From extraction profiles, different kinetic
      behaviors of flavor compounds revealed that volatility is influenced by chemical
      natures (that is, molecular weight and physicochemical properties). Moreover,
      volatility was also found to be interrelated with extraction temperature and
      absorption/adsorption on the fiber's surface. Through mathematical modeling, the
      kinetic constants of these volatile compounds were computed, and their release
      profiles were determined. Finally, it was observed that an increase of ethanol (a
      competitive interference compound to flavor compounds) could decrease the
      extraction efficiency. Our studies indicated that this approach might be a rapid
      and practical method that would provide a better understanding of flavor release
      behavior from alcoholic beverages. PRACTICAL APPLICATION: The proposed approach
      may provide a simple and fast method in predicting the performance of key aroma
      esters in different alcoholic beverages. It could also be a practical way in
      quality control during the production of alcoholic beverage by monitoring key
      aroma esters.

PMID- 22132703
TI  - Work-related suicide in Victoria, Australia: a broad perspective.
AB  - While unintentional work-related injury is increasingly recognised as important
      and preventable, population studies of the full range of work related suicides
      have received less attention. The objective of this study is to investigate the
      epidemiology of work-related suicide in Victoria, July 2000-December 2007. The
      study draws on a database of all work-related deaths reported to the Victorian
      Coroner, inclusive of broadly defined work-relatedness. Inclusion criteria for
      work-related suicide were at least one of: suicide means was work related, work
      stressors were identified in police reports to the Coroners or the Coroner's
      finding, the suicide method involved another person's work (e.g. rail suicide,
      heavy vehicle) or the suicide location was a workplace. Cases still open for
      investigation were excluded. Of 642 work-related suicides, 55% had an association
      with work stressors; 32% jumped or lay in front of a train or heavy vehicle; 7%
      involved a work location and 6% involved work agents. Work stressor cases
      identified included business difficulties, recent or previous work injury,
      unemployment/redundancy or conflict with supervisors/colleagues (including
      workplace bullying). Work-related suicide is a substantial problem, for which few
      detailed population wide studies are available. Further research is required to
      understand the contribution of work stressors and effective interventions.

PMID- 22132702
TI  - Presteady state kinetic investigation of the incorporation of anti-hepatitis B
      nucleotide analogues catalyzed by noncanonical human DNA polymerases.
AB  - Antiviral nucleoside analogues have been developed to inhibit the enzymatic
      activities of the hepatitis B virus (HBV) polymerase, thereby preventing the
      replication and production of HBV. However, the usage of these analogues can be
      limited by drug toxicity because the 5'-triphosphates of these nucleoside
      analogues (nucleotide analogues) are potential substrates for human DNA
      polymerases to incorporate into host DNA. Although they are poor substrates for
      human replicative DNA polymerases, it remains to be established whether these
      nucleotide analogues are substrates for the recently discovered human X- and Y
      family DNA polymerases. Using presteady state kinetic techniques, we have
      measured the substrate specificity values for human DNA polymerases beta, lambda,
      eta, iota, kappa, and Rev1 incorporating the active forms of the following anti
      HBV nucleoside analogues approved for clinical use: adefovir, tenofovir,
      lamivudine, telbivudine, and entecavir. Compared to the incorporation of a
      natural nucleotide, most of the nucleotide analogues were incorporated less
      efficiently (2 to >122,000) by the six human DNA polymerases. In addition, the
      potential for entecavir and telbivudine, two drugs which possess a 3'-hydroxyl,
      to become embedded into human DNA was examined by primer extension and DNA
      ligation assays. These results suggested that telbivudine functions as a chain
      terminator, while entecavir was efficiently extended by the six enzymes and was a
      substrate for human DNA ligase I. Our findings suggested that incorporation of
      anti-HBV nucleotide analogues catalyzed by human X- and Y-family polymerases may
      contribute to clinical toxicity.

PMID- 22132704
TI  - HRT misuse and the osteoporosis epidemic.
AB  - A new study by Karim and colleagues has highlighted the intriguing issue of the
      consequences of cessation of long-term postmenopausal hormone use. While
      potential reductions in breast cancer risk and in the incidence of newly
      diagnosed breast cancer in the era after the Women's Health Initiative study have
      been heavily debated, the implications of withdrawal from hormone therapy for
      bone health and fracture risk have remained outside the main scope. This new
      study has now demonstrated that there is a very clear downside in skeletal
      outcome that should be considered while evaluating the pros and cons of
      discontinuing hormone therapy. During 532 686 person-years of observation and a
      follow-up period of 6.5 years, a 55% increased risk for hip fracture was observed
      in women who stopped hormone therapy. In view of the dramatic decline in the
      number of hormone users all around the world, this mini-review discusses the
      'neglected' skeletal outcomes of such global trends.

PMID- 22132705
TI  - The genetic signature of perineuronal oligodendrocytes reveals their unique
      phenotype.
AB  - Oligodendrocytes--best known for assembling central nervous system myelin--can be
      categorized as precursors, myelin-forming cells and non-myelinating perineuronal
      cells. Perineuronal oligodendrocytes have been well characterized morphologically
      and ultrastructurally, but knowledge about their function remains scanty. It has
      been proposed that perineuronal oligodendrocytes support neurons and, following
      injury, transform into myelin-synthesizing cells. Recent findings implicating
      perineuronal oligodendrocytes in cytoarchitectural abnormalities in the
      prefrontal cortex of schizophrenia and other psychiatric disorders shed new light
      on these cells. We have obtained the genetic signature of perineuronal
      oligodendrocytes by identifying gene expression differences between
      oligodendrocyte subpopulations using cell-specific tags, microarray technology,
      quantitative time-resolved polymerase chain reaction and bioinformatics tools. We
      show that perineuronal cells are the progeny of oligodendrocyte progenitors and,
      hence, are members of the oligodendrocyte lineage. Physiologically they exhibit a
      novel phenotype. Their expression of PDGFR-alphabeta and its growth factor ligand
      PDGF-CC sets them apart from members of their lineage as this receptor precludes
      their response to the same growth factors that act on myelinating cells. Their
      coordinate expression and context-specific usage of transcription factors Olig2,
      Ascl1 and Pax6, together with the prominent presence of transcription factors
      Pea3, Lhx2 and Otx2--not hitherto linked to the oligodendrocyte lineage-
      suggested a cell with features that blur the boundary between a neuron and a
      glial cell. But they also maintain a reservoir of untranslated transcripts
      encoding major myelin proteins presumably for a demyelinating episode. This first
      molecular characterization of perineuronal oligodendrocytes revealed the striking
      difference between the myelinating and non-myelinating phenotypes.

PMID- 22132706
TI  - Benefits of Reiki therapy for a severely neutropenic patient with associated
      influences on a true random number generator.
AB  - BACKGROUND: Reiki therapy is documented for relief of pain and stress. Energetic
      healing has been documented to alter biologic markers of illness such as
      hematocrit. True random number generators are reported to be affected by energy
      healers and spiritually oriented conscious awareness. METHODS: The patient was a
      then 54-year-old severely ill man who had hepatitis C types 1 and 2 and who did
      not improve with conventional therapy. He also suffered from obesity, the
      metabolic syndrome, asthma, and hypertension. He was treated with experimental
      high-dose interferon/riboviron therapy with resultant profound anemia and
      neutropenia. Energetic healing and Reiki therapy was administered initially to
      enhance the patient's sense of well-being and to relieve anxiety. Possible
      effects on the patient's absolute neutrophil count and hematocrit were
      incidentally noted. Reiki therapy was then initiated at times of profound
      neutropenia to assess its possible effect on the patient's absolute neutrophil
      count (ANC). Reiki and other energetic healing sessions were monitored with a
      true random number generator (RNG). RESULTS: Statistically significant
      relationships were documented between Reiki therapy, a quieting of the
      electronically created white noise of the RNG during healing sessions, and
      improvement in the patient's ANC. The immediate clinical result was that the
      patient could tolerate the high-dose interferon regimen without missing doses
      because of absolute neutropenia. The patient was initially a late responder to
      interferon and had been given a 5% chance of clearing the virus. He remains clear
      of the virus 1 year after treatment. CONCLUSIONS: The association between changes
      in the RNG, Reiki therapy, and a patient's ANC is the first to the authors'
      knowledge in the medical literature. Future studies assessing the effects of
      energetic healing on specific biologic markers of disease are anticipated.
      Concurrent use of a true RNG may prove to correlate with the effectiveness of
      energetic therapy.

PMID- 22132707
TI  - Is tongxinluo more effective than isosorbide dinitrate in treating angina
      pectoris? A systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Tongxinluo (TXL), consisting of 12 Chinese Materia Medica items
      catalogued in the Chinese Pharmacopoeia, is commercially available in China,
      South Korea, and Russia. Hundreds of randomized clinical trials (RCTs) on TXL in
      treating cardiovascular diseases were conducted and published in China. This
      study provides a comprehensive Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA)-compliant systematic review with sensitivity and
      subgroup analyses to evaluate the evidence about whether TXL is more effective
      than isosorbide dinitrate (ISDN) in treating ischemic heart disease, particularly
      angina pectoris. METHODS: RCTs published between 1996 and 2010 on TXL versus ISDN
      in treating angina pectoris for at least 4 weeks were retrieved from eight
      bibliographical databases (e.g., MEDLINE,((r)) PubMed, Chinese National Knowledge
      Infrastructure, Cochrane Library, and WanFang Data). The quality of RCTs was
      assessed with the Jadad scale. Meta-analysis was performed to estimate the
      overall effects based on symptomatic and electrocardiographic (ECG) improvements.
      Subgroup analysis, sensitivity analysis, and meta-regression were conducted on
      the study characteristics of RCTs. RESULTS: Twenty (20) RCTs with a total of 1936
      participants were included after eligibility assessment. The Jadad score of all
      included studies was 2. The means of summary odds ratios (ORs) for comparing TXL
      and nitrates were 3.30 (95% confidence interval [CI] 2.37-4.58) by symptoms
      (n=20) and 2.38 (95% CI 1.846-3.09) by ECG (n=18). There was a significant
      correlation of ORs between symptoms and ECG (rho=0.77 and p=0.00026). Subgroup
      analysis, sensitivity analysis, and meta-regression found no significant
      difference in overall effects among all study characteristics except the years of
      publication (p=0.0409). CONCLUSIONS: The meta-analysis of 20 eligible RCTs
      demonstrates moderate evidence that TXL is more effective than ISDN for treating
      angina pectoris. This result warrants further RCTs of multicenters/countries,
      larger sample sizes, and higher quality.

PMID- 22132708
TI  - Pharmacokinetics of oral rufinamide in dogs.
AB  - The objective of this study was to determine the pharmacokinetic properties and
      short-term adverse effect profile of single-dose oral rufinamide in healthy dogs.
      Six healthy adult dogs were included in the study. The pharmacokinetics of
      rufinamide were calculated following administration of a single mean oral dose of
      20.0 mg/kg (range 18.6-20.8 mg/kg). Plasma rufinamide concentrations were
      determined using high-performance liquid chromatography, and pharmacokinetic data
      were analyzed using commercial software. No adverse effects were observed. The
      mean terminal half-life was 9.86 +/- 4.77 h. The mean maximum plasma
      concentration was 19.6 +/- 5.8 MUg/mL, and the mean time to maximum plasma
      concentration was 9.33 +/- 4.68 h. Mean clearance was 1.45 +/- 0.70 L/h. The area
      under the curve (to infinity) was 411 +/- 176 MUg . h/mL. Results of this study
      suggest that rufinamide given orally at 20 mg/kg every 12 h in healthy dogs
      should result in a plasma concentration and half-life sufficient to achieve the
      therapeutic level extrapolated from humans without short-term adverse effects.
      Further investigation into the efficacy and long-term safety of rufinamide in the
      treatment of canine epilepsy is warranted.

PMID- 22132709
TI  - Comparing oil based ointment versus standard practice for the treatment of
      moderate burns in Greece: a trial based cost effectiveness evaluation.
AB  - BACKGROUND: The local treatment of burn wounds has long been a subject of debate.
      The objective of this study was to compare the cost and the effectiveness of
      Moist Exposed Burn Ointment -MEBO versus a combination of povidone iodine plus
      bepanthenol cream for partial thickness burns. METHODS: The study was carried out
      in the Burn Center of a state hospital in Athens, Greece. 211 patients needing
      conservative therapy were prospectively selected according to the depth of the
      burn wound. The treatment was allocated according to the Stratified Randomization
      Design. The outcomes measured were mean cost of in-hospital stay, rate of
      complications, time of 50% wound healing, pain scores, in hospital stay
      diminution. We have adopted a societal perspective. RESULTS: In the total groups
      MEBO presented lower cost, (although not significantly different: p = 0.10) and
      better effectiveness. The data suggest that MEBO is the dominant therapy for
      superficial partial burn wound with significantly lower costs and significantly
      higher effectiveness due to a lesser time of recovery and consequently lower time
      of hospitalization and follow-up. MEBO presented similar percentages of
      complications with the comparator, lower pain levels and smaller time of no
      healthy appearance of the burn limits for superficial partial thickness burns.
      CONCLUSIONS: The data suggested that topical application of MEBO may be
      considered for further investigation as a potential first-line treatment modality
      for superficial partial thickness burns. TRIAL REGISTRATION: The trial has been
      registered on the International Standard Randomised Controlled Trial Number
      Register (ISRCTN) and given the registration number ISRCTN74058791.

PMID- 22132710
TI  - Beyond cognitive-behavioral therapy for fibromyalgia: addressing stress by
      emotional exposure, processing, and resolution.
AB  - I comment on the well-designed trial by Alda and colleagues reported in a recent
      issue of Arthritis Research and Therapy which demonstrated some benefits of
      cognitive-behavioral therapy (CBT) for fibromyalgia (FM). CBT in this and other
      studies provides statistically significant but rather modest benefits for FM.
      This may be because CBT does not directly address the high rates of
      victimization, post-traumatic stress disorder, and emotional avoidance
      experienced by a substantial number of patients with FM. Interventions that
      encourage emotional exposure, processing, and resolution of stressful or
      traumatic experiences and relationships hold potential for larger effects for
      many patients and need to be tested.

PMID- 22132711
TI  - Prospective comparisons of intravitreal injections of triamcinolone acetonide and
      bevacizumab for macular oedema due to branch retinal vein occlusion.
AB  - PURPOSE: To compare the efficacy of intravitreal injections of triamcinolone
      acetonide (TA) and that of bevacizumab for macular oedema because of branch
      retinal vein occlusion (BRVO). DESIGN: Prospective, comparative, randomized,
      interventional clinical trial. METHODS: Forty-three eyes of 43 patients with
      macular oedema because of BRVO were randomly assigned to 4-mg intravitreal
      injections of TA (IVTA)(21 patients, IVTA group) or 1.25-mg intravitreal
      injections of bevacizumab (IVB) (22 patients, IVB group) and followed for 12
      months. No additional treatments were administered for 3 months after the initial
      injection; additional injections were administered when macular oedema recurred
      between 3 and 12 months after the initial injection. The best-corrected visual
      acuity (BCVA) and the central retinal thickness (CRT) were measured at baseline
      and monthly. The main outcome measures were changes in the logarithm of the
      minimal angle of resolution BCVA and CRT from baseline to 12 months. RESULTS:
      Eighteen eyes of 18 patients in the IVTA group and 18 eyes of 18 patients in the
      IVB group completed follow-up at 12 months. The mean improvements in BCVA from
      baseline to 12 months were 0.12 in the IVTA group and 0.33 in the IVB group,
      which was significantly (p = 0.032) higher than in the IVTA group. There was no
      significant difference between the two groups in the mean reduction in CRT from
      baseline to 12 months after the initial injection. Two eyes in the IVTA group
      required intraocular pressure-lowering medications. CONCLUSION: Intravitreal
      injection of bevacizumab may be of greater benefit than that of TA for macular
      oedema because of BRVO.

PMID- 22132712
TI  - Disappearing and reappearing differences in drug-eluting stent use by race.
AB  - RATIONALE, AIMS AND OBJECTIVES: Drug-eluting coronary stents (DES) rapidly
      dominated the marketplace in the United States after approval in 2003, but
      utilization rates were initially lower among African American patients. We assess
      whether racial differences persisted as DES diffused into practice. METHODS:
      Medicare claims data were used to identify coronary stenting procedures among
      elderly patients with acute coronary syndromes (ACS). Regression models of the
      choice of DES versus bare mental stent controlled for demographics, ACS type, co
      morbidities and hospital characteristics. Diffusion was assessed in the short run
      (2003-2004) and long run (2007), with the effect of race calculated to allow for
      time-varying effects. RESULTS: The sample included 381,887 Medicare beneficiaries
      treated with stent insertion; approximately 5% were African American. Initially
      (May 2003-February 2004), African American race was associated with lower DES use
      compared to other races (44.3% versus 46.5%, P < 0.01). Once DES usage was high
      in all patients (March-December 2004), differences were not significant (79.8%
      versus 80.3%, P = 0.45). Subsequent concerns regarding DES safety caused
      reductions in DES use, with African Americans having lower use than other racial
      groups in 2007 (63.1% versus 65.2%, P < 0.01). CONCLUSIONS: Racial disparities in
      DES use initially disappeared during a period of rapid diffusion and high usage
      rates; the reappearance of disparities in use by 2007 may reflect DES use
      tailored to unmeasured aspects of case mix and socio-economic status. Further
      work is needed to understand whether underlying differences in race reflect
      decisions regarding treatment appropriateness.

PMID- 22132713
TI  - An inexpensive method of small paraffin tissue microarrays using mechanical
      pencil tips.
AB  - BACKGROUND: Tissue microarray technology has provided a high throughput means of
      evaluating potential biomarkers in archival pathological specimens. This study
      was carried out in order to produce tissue microarray blocks using mechanical
      pencil tips without high cost. METHOD: Conventional mechanical pencil tips
      (Rotring Tikky II Mechanical Pencil 1.0 mm) were used to cut out 1 mm wax
      cylinders from the recipient block, creating from 36 to 72 holes. Three cores of
      tumor areas were punched out manually by using the mechanical pencil tips from
      donor paraffin embedded tissue blocks and transferred to the holes of the
      paraffin tissue microarrays. RESULTS: This technique was easy and caused little
      damage to the donor blocks. We successfully performed H&E slides and
      immunodetection without substantial tissue cylinder loss. CONCLUSION: Our
      mechanical pencil tip technique is the most inexpensive easy technique among the
      literature. It also takes a reasonable amount of time and reduces antibody
      consumption during immunohistochemistry.

PMID- 22132714
TI  - Characteristics of grape seed and oil from nine Turkish cultivars.
AB  - Percentages of crude oil, protein, fibre and ash of grape seeds obtained from
      Turkish cultivars were of the ranges 5.40-10.79, 5.24-7.54, 17.6-27.1, and 1.2
      2.6, respectively. The highest crude oil, crude protein and crude fibre were
      determined in Siyah pekmezlik, Karadimrit and Antep grape seeds. The energy
      values of seeds were established to be between 102.28 and 148.07 kcal g(-1).
      Potassium and calcium contents of seed samples were found to be at high levels
      compared to sodium. The seeds contained 686-967 ppm of Na, 2468-3618 ppm of K and
      2373-4127 ppm of Ca. The refractive index, relative density, acidity,
      saponification value, unsaponifiable matter and iodine value of seed oils were
      determined to be in the ranges 1.474-1.477 [Formula: see text], 0.909-0.934 25/25
      degrees C, 0.74-1.24%, 181-197, 0.91-1.66%, and 126-135, respectively. The main
      fatty acids were of the ranges 60.7-68.5% linoleic, 16.1-23.4% oleic and 8.0
      10.2% palmitic. The highest percentages of linoleic acid (68.5%) was determined
      in Siyah pekmezlik seed oil.

PMID- 22132715
TI  - Sexual dysfunction is correlated with tenderness in female fibromyalgia patients.
AB  - OBJECTIVES: The purpose of the current study was to evaluate sexual dysfunction
      among female fibromyalgia syndrome (FMS) patients. METHODS: Fifty female subjects
      were recruited and were asked to complete a questionnaire regarding sexual
      functioning. The control group included fifty-five healthy age-matched
      volunteers. The participants underwent a physical examination and tender point
      assessment was performed using manual palpation. All participants filled out the
      Arizona Sexual Experience Scale, which evaluates five areas of sexual
      functioning: sexual drive, sexual arousal, vaginal wetting, orgasm and sexual
      satisfaction. RESULTS: FMS patients had significantly lower scores on all five
      aspects of sexual function assessed. A positive correlation was observed between
      the sexual drive score, signifying a decrease in sexual drive, and the number of
      tender points documented on examination. Similarly, a positive correlation was
      observed between the sexual satisfaction scale (indicating decreasing levels of
      sexual satisfaction) and the number of tender points documented. A positive
      correlation was demonstrated between the sexual arousal and orgasmatic scales and
      between the tender point counts, indicating a decrease in sexual arousal and in
      orgasmatic function in correlation with an increasing number of tender points.
      CONCLUSIONS: The results of the current study indicate a multi-factorial sexual
      dysfunction among female FMS patients. All stages of sexual functioning,
      evaluated were significantly disturbed in comparison with the healthy controls.
      Physicians treating FMS patients should be aware of, and actively inquire about,
      sexual dysfunction as part of a multi-disciplinary evaluation of such patients.

PMID- 22132716
TI  - Integrative review of graduate entry programs in nursing.
AB  - In this integrative review, the authors report on, summarize, and analyze
      research conducted on non-nurse college graduates enrolled in master's degree
      programs in nursing in the United States and Canada, leading to preparation for
      advanced practice nurse roles. This review demonstrated that non-nurse college
      graduates successfully develop into registered nurses and advanced practice
      registered nurses (APRNs) or certified nurse-midwives (CNMs). What is
      conspicuously absent in the literature is articulation of the process whereby
      college graduates become nurses and APRNs or CNMs. Given the expansion of
      graduate entry programs for non-nurse college graduates, along with the recent
      clarion call to move advanced practice nursing to the postgraduate level, it is
      time to examine the process. Understanding the process will help faculty refine
      pedagogy and curricula to support students' transition from non-nurse to both
      nurse and APRN or CNM.

PMID- 22132717
TI  - Nursing staff perceptions of student contributions in clinical settings.
AB  - Because nursing is a practice discipline, students are placed in clinical
      settings to collaborate with professional nurses in caring for patients. This
      descriptive study aimed to explore the benefits and limitations of undergraduate
      nursing students in the clinical setting. A 54-item instrument, Nursing Students'
      Contributions to Clinical Agencies, was used to collect data from staff nurses (N
      = 84) at three hospitals. The instrument also provided space for participants to
      share qualitative data, which revealed perceptions with which staff nurses were
      likely to agree and three key themes: Eager to Learn, Willing to Help, and
      Serving Their Time. The major implication for students is that they are often
      judged on their assertiveness skills and should offer assistance so they appear
      eager to learn. Faculty must ascertain that students understand their objectives
      for the clinical rotation and share those objectives with the staff nurses to
      enhance their learning experience.

PMID- 22132718
TI  - Assessing the reliability, validity, and use of the Lasater Clinical Judgment
      Rubric: three approaches.
AB  - The purpose of this article is to summarize the methods and findings from three
      different approaches examining the reliability and validity of data from the
      Lasater Clinical Judgment Rubric (LCJR) using human patient simulation. The first
      study, by Adamson, assessed the interrater reliability of data produced using the
      LCJR using intraclass correlation (2,1). Interrater reliability was calculated to
      be 0.889. The second study, by Gubrud-Howe, used the percent agreement strategy
      for assessing interrater reliability. Results ranged from 92% to 96%. The third
      study, by Sideras, used level of agreement for reliability analyses. Results
      ranged from 57% to 100%. Findings from each of these studies provided evidence
      supporting the validity of the LCJR for assessing clinical judgment during
      simulated patient care scenarios. This article provides extensive information
      about psychometrics and appropriate use of the LCJR and concludes with
      recommendations for further psychometric assessment and use of the LCJR.

PMID- 22132719
TI  - Use of a virtual community to contextualize learning activities.
AB  - This article reports the experiences of two schools of nursing using a virtual
      community (VC) and how integrated teaching strategies were developed, which
      lessened the gap between didactic and clinical applications. Exemplars for
      nursing education practice are highlighted. The term context as used in nursing
      education, means placing the particular concept, topic, or skill in a setting
      where it is given enhanced meaning to the learner. This strategy allows nursing
      students to better retain knowledge and apply new concepts. The VC detailed in
      this article provides students with such context to enhance learning. It also
      enhances student engagement by adding an additional level of complexity and
      richness. One advantage of the VC is the ability to present nursing education
      beyond the acute inpatient care setting. The VC allows students to observe how
      illness progresses and exacerbations occur. This pedagogical shift moves from
      content-driven didactic instruction to a learner-centered approach.

PMID- 22132720
TI  - Conducting multisite research studies in nursing education: brief practice of CPR
      skills as an exemplar.
AB  - Few large, multisite studies have been conducted in nursing education, and
      literature pertaining to conducting those studies is lacking. We recently
      completed a randomized trial to examine the effects of brief practice on nursing
      students' retention of CPR psychomotor skills. The purpose of this article is to
      describe strategies for implementing a multisite study in nursing education,
      using our research as an exemplar. Strategies are presented for structuring a
      multisite study; selecting, preparing, and communicating with team members across
      sites; selecting sites; recruiting and retaining participants; managing the
      technical aspects of an intervention; and collecting and managing data. Ethical
      considerations also are explored.

PMID- 22132721
TI  - Videodermoscopic pattern analysis of acral melanocytic nevi.
AB  - Three major and three minor types of acral melanocytic lesions have been
      described: parallel furrow, lattice-like, fibrillar, reticular, homogeneous and
      globular. To examine the dermoscopic patterns of acral melanocytic lesions and to
      investigate the association of these patterns with clinical features. This study
      included 419 acral melanocytic lesions of 295 patients. Dermoscopic images were
      stored in a standardized digital system and assessed. The incidence rates of the
      patterns were as follows: parallel furrow (62.5%), reticular (12.2%), globular
      (7.6%), fibrillar (5.0%), lattice-like (4.3%), homogeneous (3.8%), non-typical
      (3.8%), globulostreak-like (0.5%) and parallel ridge (0.2%). There was a
      significant association between pattern and diameter; nevi showing globular
      pattern were significantly smaller than those showing lattice-like pattern. There
      was a significant correlation between pattern and localization. The fibrillar
      pattern was observed more commonly on the feet, and the lattice-like pattern was
      seen almost entirely on the hands. Homogeneous and globular patterns were
      proportionately more common on the feet than on the hands. A significant
      association was found between patterns and colors. Compared with the lattice-like
      pattern, parallel furrow, fibrillar and homogeneous patterns were lighter in
      color; the globular pattern was darker than the homogeneous pattern. There was no
      significant correlations between pattern and clinical presentation. In
      conclusion, unlike all other studies, in the present study, the two most common
      patterns following the parallel furrow pattern were reticular and globular, which
      are minor patterns. Besides the differences in pattern distribution and inherent
      variability in individual assessment, the age of the study group and location of
      nevi influence the pattern, possibly in association with race.

PMID- 22132722
TI  - Phacoemulcification with intravitreal bevacizumab injection in patients with
      cataract and coexisting diabetic retinopathy: prospective randomized study.
AB  - OBJECTIVE: To evaluate efficacy of intravitreal injection of bevacizumab at the
      time of cataract surgery on the postoperative progression of diabetic retinopathy
      (DR) and diabetic maculopathy. METHODS: Patients were randomized to a
      standardized procedure of phacoemulsification with intraocular lens implantation
      alone (control group; 30 eyes) or to receive 1.25 mg intravitreal bevacizumab
      (0.05 mL of solution prepared from avastin, 100 mg/4 mL vial) at the end of
      surgery (IVB group; 27 eyes). Efficacy measures included best-corrected visual
      acuity (BCVA) testing, optical coherence tomography (OCT), and ophthalmoscopic
      examination at each postoperative visit during a 6-month follow-up. RESULTS:
      There were no significant differences in central macular thickness (CMT), BCVA,
      or systemic condition between the control and IVB groups at baseline. Progression
      of diabetic maculopathy occurred in 15 eyes (50%) in the control group and 2 eyes
      (7.4%) in the intervention group (P = 0.0008). There was no statistically
      significant difference in postoperative visual acuity between the 2 groups after
      6 months (P = 0.5). Five eyes in the control group and 1 eye in the intervention
      group progressed to neovascular glaucoma. Difference in mean postoperative CMT
      was not statistically significant between both groups (P = 0.54). CONCLUSIONS:
      Intravitreal administration of 1.25 mg bevacizumab at the time of cataract
      surgery was safe and effective in preventing the progression of DR and diabetic
      maculopathy in patients with cataract and DR.

PMID- 22132723
TI  - Low dose hyper-radiosensitivity is eliminated during exposure to cycling hypoxia
      but returns after reoxygenation.
AB  - PURPOSE: To investigate the effect of cycling hypoxia on low dose hyper
      radiosensitivity (HRS). MATERIALS AND METHODS: Human breast tumor T-47D cells
      were grown in a hypoxia workstation operated at 4% O(2) for 3-6 weeks and the
      pericellular oxygen concentration was recorded every 20 minutes. The presence of
      HRS in response to subsequent challenge irradiation was measured by clonogenic
      survival. RESULTS: T-47D cells adapted to growing with 4% O(2) in the gas phase
      but showed no HRS. However, HRS was recovered after between 48 h and two weeks of
      reoxygenation at 20% O(2). Medium transferred from the hypoxic T-47D cells
      removed HRS in recipient cells grown in ambient air. Cells irradiated with X-rays
      showed a shallower HRS-'dip' and a lower d(c)-value (dose where the change from
      the hypersensitive to the induced repair response is 63% complete) compared to
      cells irradiated with (60)Co gamma-rays. CONCLUSIONS: Cycling hypoxia transiently
      eliminates HRS in T-47D cells in vitro. This may partly explain the diverging
      results of in vivo studies of HRS. The effect of cycling hypoxia on HRS is
      comparable to our previous findings for T-47D cells receiving medium transfer
      from cells irradiated with 0.3 Gy at 0.3 Gy/h.

PMID- 22132724
TI  - Inhibitory effects of nisin against Clostridium perfringens food poisoning and
      nonfood-borne isolates.
AB  - The enterotoxigenic Clostridium perfringens type A is the causative agent of C.
      perfringens type A food poisoning (FP) and nonfood-borne (NFB) human
      gastrointestinal diseases. Due to its ability to form highly resistant
      endospores, it has become a great concern to the meat industry to produce meat
      free of C. perfringens. In this study, we evaluated the antimicrobial effect of
      nisin against C. perfringens FP and NFB isolates. No inhibitory effect of nisin
      was observed against germination of spores of both FP and NFB isolates in
      laboratory medium. However, nisin effectively arrested outgrowth of germinated
      spores of C. perfringens in rich medium. Interestingly, germinated spores of NFB
      isolates possessed higher resistance to nisin than that of FP isolates.
      Furthermore, nisin exhibited inhibitory effect against vegetative growth of both
      FP and NFB isolates in laboratory medium, with vegetative cells of NFB isolates
      showing higher resistance than that of FP isolates. However, the antimicrobial
      activity of nisin against C. perfringens was significantly decreased in a meat
      model system. In conclusion, although nisin showed inhibitory effect against
      spore outgrowth and vegetative cells of C. perfringens FP and NFB isolates in
      laboratory conditions, no such effect was observed against C. perfringens spores
      inoculated into a meat model system.

PMID- 22132725
TI  - An aspartate residue in the external vestibule of GLYT2 (glycine transporter 2)
      controls cation access and transport coupling.
AB  - Synaptic glycine levels are controlled by GLYTs (glycine transporters). GLYT1 is
      the main regulator of synaptic glycine concentrations and catalyses Na+-Cl-
      glycine co-transport with a 2:1:1 stoichiometry. In contrast, neuronal GLYT2
      supplies glycine to the presynaptic terminal with a 3:1:1 stoichiometry. We
      subjected homology models of GLYT1 and GLYT2 to molecular dynamics simulations in
      the presence of Na+. Using molecular interaction potential maps and in silico
      mutagenesis, we identified a conserved region in the GLYT2 external vestibule
      likely to be involved in Na+ interactions. Replacement of Asp471 in this region
      reduced Na+ affinity and Na+ co-operativity of transport, an effect not produced
      in the homologous position (Asp295) in GLYT1. Unlike the GLYT1-Asp295 mutation,
      this Asp471 mutant increased sodium leakage and non-stoichiometric uncoupled ion
      movements through GLYT2, as determined by simultaneously measuring current and
      [3H]glycine accumulation. The homologous Asp471 and Asp295 positions exhibited
      distinct cation-sensitive external accessibility, and they were involved in Na+
      and Li+-induced conformational changes. Although these two cations had opposite
      effects on GLYT1, they had comparable effects on accessibility in GLYT2,
      explaining the inhibitory and stimulatory responses to lithium exhibited by the
      two transporters. On the basis of these findings, we propose a role for Asp471 in
      controlling cation access to GLYT2 Na+ sites, ion coupling during transport and
      the subsequent conformational changes.

PMID- 22132726
TI  - Associations of traffic safety attitudes and ticket fixing behaviours with the
      crash history of Pakistani drivers.
AB  - The study assessed whether traffic safety attitudes and ticket fixing behaviours
      were associated with the crash history. A total of 4018 male drivers from Lahore
      city participated in this cross sectional study. Most were aged 18-30 years
      (58.7%, n = 2362), 71.9% (n = 2887) received a traffic ticket, 66.5% (n = 2672)
      reported previous traffic ticket fixing and 71.3% (n = 2865) considered crashes
      as being the will of God. Crash history was reported by 95.4% (n = 3821) of
      drivers, and 58.2% of them reported being involved in a road traffic crash. The
      likelihood of reporting a previous crash was higher in those who had received a
      traffic sign violation ticket [adjusted odds ratio (aOR) = 1.40; 95% confidence
      interval (95%CI) = 1.15-1.72], were involved in traffic ticket fixing (aOR =
      1.28; 95%CI = 1.07-1.53), and considered crashes as will of God (aOR = 1.86; 95%
      CI = 1.57-2.22). These results suggested the need for improving traffic
      enforcement monitoring and safety education in Pakistan.

PMID- 22132727
TI  - Evaluation and management of depressive and anxiety symptoms in midlife.
AB  - OBJECTIVES: Evaluation and management of anxiety and depression during the
      menopausal transition are complicated by the overlap between some symptoms of
      affective disorder with those of menopausal symptoms, and also by inconsistencies
      in the literature regarding the relationship between the menopausal transition
      and affective disorders. METHODS: We have reviewed key studies over the past
      three decades addressing depression and anxiety during the menopause transition,
      in order to present a practical, clinical approach to the evaluation and
      management of anxiety and depressive symptoms at midlife. RESULTS: Symptoms of
      anxiety and depression are common at midlife and may coincide with menopausal
      symptoms. Some menopausal symptoms are also symptoms of anxiety and/or
      depression. Management should include treatment of troublesome menopausal
      symptoms, providing strategies to deal with psychosocial stressors, and exclusion
      of clinically significant anxiety and depressive disorders. Interventions such as
      exercise and cognitive behavior therapy may improve mood and general health at
      menopause, and a multifocal approach is recommended. Depression of greater than
      moderate severity requires treatment with an antidepressant. Some selective
      serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors
      may also improve vasomotor symptoms and these should be considered in women with
      both affective disorder and vasomotor symptoms. CONCLUSIONS: There is no clear
      evidence that the menopause transition alone increases the risk of clinically
      significant affective disorders, except in women with risk factors such as
      psychosocial stressors, severe and prolonged vasomotor symptoms and a previous
      history of affective disorders. Nevertheless, anxiety and depression are common
      in women and clinicians should be alert to the symptoms of these conditions at
      all encounters.

PMID- 22132728
TI  - Recovery of axonal myelination sheath and axonal caliber in the mouse corpus
      callosum following damage induced by N,N-diethyldithiocarbamate.
AB  - Disulfiram is an aldehyde dehydrogenase inhibitor used for the treatment of
      alcohol dependence and of cocaine addiction. It has been demonstrated that
      subchronic administration of disulfiram or N,N-diethyldithiocarbamate (DEDTC),
      the main derivative of disulfiram, to rats can produce central-peripheral distal
      axonopathy. However, few data regarding the axonal effects of these compounds in
      the central nervous system exist. Our previous studies have revealed DEDTC
      induced axonal damage in the mouse brain during the course of postnatal
      development, together with alterations in axonal pathfinding and in the
      myelination process, with partial recovery during the post-treatment period. In
      order to gather new data about how this axonal damage and recovery occurs in the
      central nervous system, we performed an ultrastructural analysis of the axons
      located in the corpus callosum from mice treated with DEDTC during postnatal
      development. The axonal caliber throughout the axonal area, the maximum axonal
      diameter, the maximum fiber diameter, and the axonal circularity, at different
      postnatal stages [from postnatal day (P)9 to P30], were analyzed. In addition,
      parameters related to the myelinization process (number of myelinated axons,
      sheath thickness, and the ratio of myelinated axons to total axons) were
      evaluated. A reduction in the average value of axonal caliber during treatment
      and a delay in the axonal myelination process were detected. Whereas early
      recovery of individual axons occurred after treatment (P22), complete recovery of
      myelinated axons occurred at late postnatal stages (P42). Therefore, chronic
      treatment with dithiocarbamates requires periods of rest to encourage the
      recovery of myelinated axons.

PMID- 22132729
TI  - Comparison of two homogeneous cell-based kinase assays for JAK2 V617F: SureFire
      pSTAT5 and GeneBLAzer fluorescence resonance energy transfer assays.
AB  - The Janus kinase (JAK)/signal transducer and activator of transcription (STAT)
      signaling pathway plays an important role in cellular responses to cytokines and
      growth factors. Recent studies have identified a recurrent somatic activating
      mutation (JAK2 V617F) in majority of patients with myeloproliferative disorders
      (MPDs). Development of drugs that target JAK2 V617F is, therefore, of therapeutic
      relevance. To discover small molecule inhibitors for this target, robust and
      reliable cell-based assays are important. Here, we present a comparison of two
      homogeneous, 384-well plate-based cellular assays using Invitrogen's
      CellSensor(r) JAK2 V617F interferon regulatory factor-1 (irf1)-beta-lactamase
      (bla) human erythroleukemia line (HEL): (1) SureFire(r) pSTAT5 AlphaScreen(r)
      assay from PerkinElmer; and (2) GeneBLAzer(r) fluorescence resonance energy
      transfer assay from Invitrogen. HEL cells are growth factor-independent due to
      JAK2 V617F mutation that causes constitutive STAT5 activation. The SureFire assay
      measures levels of phosphorylated STAT5 downstream of JAKs, while the GeneBLAzer
      assay is a reporter assay that monitors bla activity further downstream of STAT5.
      Evaluation of a number of chemically diverse JAK2 inhibitors in the two cellular
      assays yielded comparable half-maximal inhibitory concentration (IC50) values,
      boding well for the utility of these assay formats in compound profiling.

PMID- 22132730
TI  - Pharmacokinetics and bone tissue concentrations of lincomycin following
      intravenous and intramuscular administrations to cats.
AB  - The pharmacokinetic properties and bone concentrations of lincomycin in cats
      after single intravenous and intramuscular administrations at a dosage rate of 10
      mg/kg were investigated. Lincomycin minimum inhibitory concentration (MIC) for
      some gram-positive strains isolated from clinical cases was determined. Serum
      lincomycin disposition was best-fitted to a bicompartmental and a
      monocompartmental open models with first-order elimination after intravenous and
      intramuscular dosing, respectively. After intravenous administration,
      distribution was rapid (T(1/2(d)) = 0.22 +/- 0.09 h) and wide as reflected by the
      volume of distribution (V((d(ss)))) of 1.24 +/- 0.08 L/kg. Plasma clearance was
      0.28 +/- 0.09 L/h . kg and elimination half-life (T(1/2)) 3.56 +/- 0.62 h. Peak
      serum concentration (C(max)), T(max), and bioavailability for the intramuscular
      administration were 7.97 +/- 2.31 MUg/mL, 0.12 +/- 0.05 h, and 82.55 +/- 23.64%,
      respectively. Thirty to 45 min after intravenous administration, lincomycin bone
      concentrations were 9.31 +/- 1.75 MUg/mL. At the same time after intramuscular
      administration, bone concentrations were 3.53 +/- 0.28 MUg/mL. The corresponding
      bone/serum ratios were 0.77 +/- 0.04 (intravenous) and 0.69 +/- 0.18
      (intramuscular). Lincomycin MIC for Staphylococcus spp. ranged from 0.25 to 16
      MUg/mL and for Streptococcus spp. from 0.25 to 8 MUg/mL.

PMID- 22132731
TI  - Activator protein 1 (AP-1) contributes to EpCAM-dependent breast cancer invasion.
AB  - INTRODUCTION: EpCAM is a cell-surface glycoprotein that is overexpressed in the
      majority of epithelial carcinomas. However, the functional role of EpCAM in
      regulating cancer invasion remains controversial, and the mechanism(s) underlying
      EpCAM-mediated regulation of breast cancer invasion remain to be defined.
      METHODS: EpCAM expression was manipulated in breast cancer cell lines using RNA
      interference and cDNA expression constructs. Recombinant EpCAM was used to rescue
      EpCAM signaling following specific ablation of EpCAM. Protein and gene
      expression, invasion, transcription factor activity, and protein phosphorylation
      were measured using standard molecular biology techniques. RESULTS: In loss-of
      function, and gain-of-function experiments we demonstrate that EpCAM expression
      is associated with increased breast cancer invasion in vitro and in vivo. We
      demonstrate further that specific ablation of EpCAM expression is associated with
      decreased activator protein-1 (AP-1) transcription factor activity.
      Phosphoprotein analyses confirm that specific ablation of EpCAM is associated
      with decreased phosphorylation of the AP-1 subunit c-Jun. Recombinant soluble
      extracellular EpCAM (rEpCAM) is able to rescue invasion, AP-1 transcription
      factor activity, and c-Jun phosphorylation in a dose-dependent fashion.
      Pharmacologic inhibitors, and constitutively active constructs of the c-Jun N
      terminal kinase (JNK) signal transduction pathway, suggest that the impact of
      EpCAM expression on AP-1 transcription factor activity is mediated through the
      JNK pathway. In functional rescue experiments, forced expression of c-Jun rescues
      invasion in breast cancer cells following specific ablation of EpCAM.
      CONCLUSIONS: These data demonstrate for the first time that EpCAM expression can
      influence the JNK/AP-1 signal transduction pathway, and suggest that modulation
      of AP-1 transcription factor activity contributes to EpCAM-dependent breast
      cancer invasion. These data have important implications for the design and
      application of molecular therapies targeting EpCAM.

PMID- 22132732
TI  - Anticancer activity of an extract from needles and twigs of Taxus cuspidata and
      its synergistic effect as a cocktail with 5-fluorouracil.
AB  - BACKGROUND: Botanical medicines are increasingly combined with chemotherapeutics
      as anticancer drug cocktails. This study aimed to assess the chemotherapeutic
      potential of an extract of Taxus cuspidata (TC) needles and twigs produced by
      artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU).
      METHODS: Components of TC extract were identified by HPLC fingerprinting.
      Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies
      were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell
      cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma
      were determined by HPLC and the pharmacokinetic parameters were estimated using
      3p87 software. Synergistic efficacy was subjected to median effect analysis with
      the mutually nonexclusive model using Calcusyn1 software. The significance of
      differences between values was estimated by using a one-way ANOVA. RESULTS: TC
      extract reached inhibition rates of 70-90% in different human cancer cell lines
      (HL-60, BGC-823, KB, Bel-7402, and HeLa) but only 5-7% in normal mouse T/B
      lymphocytes, demonstrating the broad-spectrum anticancer activity and low
      toxicity to normal cells of TC extract in vitro. TC extract inhibited cancer cell
      growth by inducing apoptosis and G(2)/M cell cycle arrest. Most interestingly, TC
      extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of
      cancer cells in vitro, with Combination Index values (CI) ranging from 0.90 to
      0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from
      0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI < 1 in A549 cells. In
      addition, the cocktail had lower cytotoxicity in normal human cell (HEL) than 5
      FU used alone. Furthermore, TC extract did not affect the pharmacokinetics of 5
      FU in rats. CONCLUSIONS: The combinational use of the TC extract with 5-FU
      displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal
      cells. These findings suggest that this cocktail may have a potential role in
      cancer treatment.

PMID- 22132733
TI  - Whole-genome SNP association analysis of reproduction traits in the Finnish
      Landrace pig breed.
AB  - BACKGROUND: Good genetic progress for pig reproduction traits has been achieved
      using a quantitative genetics-based multi-trait BLUP evaluation system. At
      present, whole-genome single nucleotide polymorphisms (SNP) panels provide a new
      tool for pig selection. The purpose of this study was to identify SNP associated
      with reproduction traits in the Finnish Landrace pig breed using the Illumina
      PorcineSNP60 BeadChip. METHODS: Association of each SNP with different traits was
      tested with a weighted linear model, using SNP genotype as a covariate and animal
      as a random variable. Deregressed estimated breeding values of the progeny tested
      boars were used as the dependent variable and weights were based on their
      reliabilities. Statistical significance of the associations was based on
      Bonferroni-corrected P-values. RESULTS: Deregressed estimated breeding values
      were available for 328 genotyped boars. Of the 62,163 SNP in the chip, 57,868 SNP
      had a call rate > 0.9 and 7,632 SNP were monomorphic. Statistically significant
      results (P-value < 2.0E-06) were obtained for total number of piglets born in
      first and later parities and piglet mortality between birth and weaning in later
      parity, and suggestive associations (P-value < 4.0E-06) for piglet mortality
      between birth and weaning in first parity, number of stillborn piglets in later
      parity, first farrowing interval and second farrowing interval. Two of the
      statistically significant regions for total number of piglets born in first and
      later parities are located on chromosome 9 around 95 and 79 Mb. The estimated SNP
      effect in these regions was approximately one piglet between the two homozygote
      classes. By combining the two most significant SNP in these regions, favourable
      double homozygote animals are expected to have 1.3 piglets (P-value = 1.69E-08)
      more than unfavourable double homozygote animals. A region on chromosome 9 (66
      Mb) was statistically significant for piglet mortality between birth and weaning
      in later parity (0.44 piglets between homozygotes, P-value = 6.94E-08).
      CONCLUSIONS: Three separate regions on chromosome 9 gave significant results for
      litter size and pig mortality. The frequencies of favourable alleles of the
      significant SNP are moderate in the Finnish Landrace population and these SNP are
      thus valuable candidates for possible marker-assisted selection.

PMID- 22132734
TI  - The yeast Golgi apparatus.
AB  - The Golgi apparatus is an organelle that has been extensively studied in the
      model eukaryote, yeast. Its morphology varies among yeast species; the Golgi
      exists as a system of dispersed cisternae in the case of the budding yeast
      Saccharomyces cerevisiae, whereas the Golgi cisternae in Pichia pastoris and
      Schizosaccharomyces pombe are organized into stacks. In spite of the different
      organization, the mechanism of trafficking through the Golgi apparatus is
      believed to be similar, involving cisternal maturation, in which the resident
      Golgi proteins are transported backwards while secretory cargo proteins can stay
      in the cisternae. Questions remain regarding the organization of the yeast Golgi,
      the regulatory mechanisms that underlie cisternal maturation of the Golgi and
      transport machinery of cargo proteins through this organelle. Studies using
      different yeast species have provided hints to these mechanisms.

PMID- 22132736
TI  - In vitro antibacterial and antifungal activities of Rhus tripartitum used as
      antidiarrhoeal in Tunisian folk medicine.
AB  - Rhus tripartitum (African sumac) is a plant commonly used in Tunisian traditional
      medicine to treat diarrhoea and dysentery. In this study, we have demonstrated
      that R. tripartitum extracts exhibited a significant broad spectrum activity
      against one or more of the test microorganisms with a zone size ranging from 8 to
      28 mm in diameter. These diameters are much higher than those obtained with
      standard antibiotics. The chloroformic extracts were found to be effective
      against bacterial and fungal strains tested, with MIC values ranging between 0.07
      and 0.62 mg mL(-1) against Staphylococcus aureus and Candida albicans. However,
      ethyl-acetate/methanol fractions showed a selective activity only against
      bacterial microorganisms with low MIC values between 0.07 and 0.15 mg mL(-1). The
      overall results suggested that the traditional use of R. tripartitum for the
      treatment of diarrhoea tract infections was attributed to the presence of
      antibacterial agents.

PMID- 22132737
TI  - Subthreshold mood symptoms in patients with fibromyalgia and rheumatoid
      arthritis.
AB  - OBJECTIVES: Although several findings have highlighted the prevalence of Axis I
      psychiatric disorders in fibromyalgia (FM) and rheumatoid arthritis (RA), very
      little information is available on the prevalence of subthreshold mood symptoms
      in these conditions. Therefore, we aimed at comparing the prevalence of
      subthreshold mood symptoms in rheumatic patients suffering from FM and RA. The
      hypothesis is that subthreshold mood symptoms are more represented in FM, given
      the evidence of higher rates of Axis I psychopathology in FM than in RA. METHODS:
      Sixty patients suffering from FM and 50 from RA, assessed according to the
      American College of Rheumatology (ACR) criteria, selected in a Rheumatology
      Department, were included in the study. The subthreshold affective symptoms were
      assessed by means of the Mood Spectrum-Self Report (MOODS-SR). RESULTS: The
      results showed that FM patients presented significantly higher scores than RA
      patients in 'mood depressive', 'cognition depressive' domains and in total
      depressive component. CONCLUSIONS: The present study demonstrates that
      subthreshold depressive symptoms are more represented in FM than in RA patients.
      This fact could play a role in the worse quality of life and in the major
      perception of pain which characterises FM.

PMID- 22132738
TI  - Pattern recognition approaches and computational systems tools for ultra
      performance liquid chromatography-mass spectrometry-based comprehensive
      metabolomic profiling and pathways analysis of biological data sets.
AB  - Metabolomics represents an emerging and powerful discipline that provides an
      accurate and dynamic picture of the phenotype of biosystems through the study of
      potential metabolites that could be used for therapeutic targets and discovery of
      new drugs. Metabolomic network construction has led to the integration of
      metabolites associated with the caused perturbation of multiple pathways. Herein,
      we present a method for the construction of efficient networks with regard to
      that Jujuboside B (JuB) protects against insomnia as a case study. UPLC/ESI
      SYNAPT-HDMS coupled with pattern recognition methods including PCA, PLS-DA, OPLS
      DA, and computational systems analysis were integrated to obtain comprehensive
      metabolomic profiling and pathways of the large biological data sets. Among the
      regulated pathways, twelve biomarkers were identified and tryptophan metabolism,
      phenylalanine, tyrosine, tryptophan biosynthesis, arachidonic acid metabolism,
      and phenylalanine metabolism related network were acutely perturbed. Results not
      only supplied a systematic view of the development and progression of insomnia
      but also were used to analyze the therapeutic effects of JuB, a widely used anti
      insomina medicine in clinics. The results showed that JuB administration could
      provide satisfactory effects on insomnia through partially regulating the
      perturbed pathway. We have constructed a metabolomic feature network of JuB to
      protect against insomnia. The most promising use in the near future would be to
      clarify pathways for the drugs and get biomarkers for these pathways, to help
      guide testable predictions, provide insights into drug action mechanisms, and
      enable us to increase research productivity toward metabolomic drug discovery.

PMID- 22132735
TI  - Epidermal growth factor receptor in breast carcinoma: association between gene
      copy number and mutations.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) is an available target of
      effective anti-EGFR therapy for human breast cancer. The aim of this study was to
      assess the presence of EGFR gene amplification and mutations in breast cancer and
      to analyze the association between the statuses of these two gene alterations.
      MATERIALS AND METHODS: EGFR gene amplification and mutations were investigated in
      formalin-fixed, paraffin-embedded tissues from 139 Chinese female patients with
      breast cancer by means of fluorescence in-situ hybridization (FISH) and
      fluorescently labeled real-time quantitative polymerase chain reaction (RT-PCR),
      respectively. RESULTS: EGFR gene amplification was observed in 46/139 (33.1%) of
      cases by FISH. Based on RT-PCR, 2/139 (1.4%) samples had EGFR gene mutations.
      Overall, only 1 (0.7%) of the cases was identified with both whole gene
      amplification and mutation, and 92 (66.2%) of cases were negative for both. High
      gene copy numbers of EGFR had significant correlation with the occurrence of EGFR
      protein expressions (P = 0.002). CONCLUSION: In this study, EGFR mutations were
      presented in only two samples, indicating that EGFR mutations should not be
      employed in future trials with anti-EGFR therapies for breast cancer. However,
      EGFR whole gene amplification is frequently observed in patients with breast
      cancer. It will be of significant interest to investigate whether EGFR gene copy
      number is a suitable screening test for EGFR-targeted therapy for breast cancer.

PMID- 22132739
TI  - Targeted overexpression of Angptl6/angiopoietin-related growth factor in the skin
      promotes angiogenesis and lymphatic vessel enlargement in response to ultraviolet
      B.
AB  - Angiogenesis is required for physiological tissue repair processes, such as
      cutaneous wound healing. However, recent studies indicate that endogenous
      angiogenic factors may enhance photo-induced skin alterations in response to
      experimental ultraviolet (UV)-B exposure. Angiopoietin-related growth factor
      (AGF), also known as angiopoietin-like protein 6 (Angptl6), is known to promote
      new blood vessel formation and vascular hyperpermeability. Importantly, epidermal
      overexpression of Angptl6/AGF in mice promotes wound healing in the skin.
      However, it remains unclear whether overexpression of Angptl6/AGF facilitates
      tissue repair processes in response to UV-B irradiation. To test this hypothesis,
      we subjected Angptl6/AGF transgenic mice to acute or chronic UV-B exposure.
      Surprisingly, transgenic mice showed enhanced photosensitivity to subthreshold
      doses of UV-B that did not induce skin alterations in wild-type littermates.
      Marked enlargement of blood vessels was observed after a single exposure to UV-B
      in Angptl6/AGF transgenic mice, although no epidermal changes were observed.
      Chronic UV-B exposure over 14 weeks promoted cutaneous skin damage in Angptl6/AGF
      transgenic mice, whereas wild-type mice showed little or no macroscopic skin
      alteration. In addition to pronounced angiogenesis and epidermal hyperplasia,
      marked enlargement of dermal lymphatic vessels was observed in UV-B-exposed
      Angptl6/AGF transgenic mice. Electron microscopy analysis further revealed that
      the number and size of collagen bundles in the dermis was markedly reduced after
      chronic UV-B exposure in Angptl6/AGF transgenic mice. Taken together, these
      results indicate that ectopic expression of Angptl6/AGF in mice likely promotes
      UV-B-induced skin alterations, and that angiogenesis could be a therapeutic
      target in prevention of skin photo-aging.

PMID- 22132740
TI  - Training nurses for interdisciplinary communication with families in the
      intensive care unit: an intervention.
AB  - BACKGROUND: Critical care nurse communication training has largely been limited
      to didactic materials, interactive training for nurse supervisors, or brief
      participatory learning programs within the context of comprehensive end-of-life
      care educational seminars. Preliminary evidence suggests that an interactive
      approach can also be effective in communication skills training for intensive
      care unit (ICU) nurses. METHODS: We implemented a 1-day educational intervention
      in five acute care hospitals within Veterans Integrated Service Network (VISN) 3
      (New York-New Jersey region) of the Department of Veterans Affairs and focused
      solely on communication skills and targeted specifically to nurses providing
      bedside care for critically ill patients. A "learner centered" approach to skills
      training that has several integral components was employed. AMONG THESE ARE: a
      cognitive, evidence-based foundation upon which to build new skills; a method
      such as role-play that allows participants to practice newly learned skills; and
      an affective component, during which trainees can freely discuss their
      impressions of the exercise or explore difficulties that may have been
      encountered. Before and after the program we conducted a detailed assessment of
      participants' self-rated communication skills and of the techniques and materials
      we used. RESULTS AND CONCLUSIONS: Post-program responses documented significant
      improvement in self-evaluated skills for each of the core tasks we assessed.
      Evidence suggests that communication with patients and families in the ICU can be
      most effectively approached in an interdisciplinary way. For nurses to fully
      realize their potential for optimal communication as members of the
      multidisciplinary team, they must be equipped with the necessary skills. We
      believe this new program helps to expand the range of approaches for training
      nurses in essential communication skills.

PMID- 22132741
TI  - Comments on DNA as a fractal antenna.

PMID- 22132742
TI  - Inhibitory effects of UV treatment and a combination of UV and dry heat against
      pathogens on stainless steel and polypropylene surfaces.
AB  - Pathogens that contaminate the surfaces of food utensils may contribute to the
      occurrence of foodborne disease outbreaks. We investigated the efficacy of UV
      treatment combined with dry heat (50  degrees C) for inhibiting 5 foodborne
      pathogens (Escherichia coli O157:H7, Salmonella Typhimurium, Pseudomonas
      aeruginosa, Listeria monocytogenes, and Staphylococcus aureus) on stainless steel
      and polypropylene surfaces in this study. We inoculated substrates with each of
      the 5 foodborne pathogens cultured on agar surface and then UV treatment alone or
      a combination of both UV and dry heat (50  degrees C) was applied for 30 min, 1
      h, 2 h, and 3 h. The initial populations of the 5 pathogens before treatment were
      8.02 to 9.18 and 8.73 to 9.16 log10 CFU/coupon on the surfaces of stainless steel
      and polypropylene coupons, respectively. UV treatments for 3 h significantly
      inhibited S. Typhimurium, L. monocytogenes, and S. aureus on the stainless steel
      by 3.06, 2.18, and 2.70 log10 CFU/coupon, and S. aureus on the polypropylene by
      3.11 log10 CFU/coupon, respectively. The inhibitory effects of the combined UV
      and dry heat treatment (50  degrees C) increased as treatment time increased,
      yielding significant reductions in all samples treated for 3 h, with the
      exception of S. aureus on polypropylene. The reduction level of E. coli O157:H7
      treated for 3 h on the surface of stainless steel and polypropylene treated was
      approximately 6.00 log10 CFU/coupon. These results indicate that combined UV and
      dry heat (50  degrees C) treatments may be effective for controlling microbial
      contamination on utensils and cooking equipment surfaces as well as in other
      related environments.

PMID- 22132745
TI  - Controlling the position of functional groups at the liquid/solid interface:
      impact of molecular symmetry and chirality.
AB  - With the aim of controlling the position of functional groups in a substrate
      supported monolayer, a new family of functionalized linear alkyl chains was
      designed and synthesized, aided by molecular mechanics and dynamics simulations
      of its two-dimensional self-assembly on graphite. The self-assembly of these
      amino functionalized diamides at the liquid/solid interface was investigated with
      scanning tunneling microscopy. Intermolecular hydrogen-bonding interactions
      involving amides, combined with the effect of molecular symmetry and chirality,
      were found to guide the self-assembly. Control of the relative position and
      orientation of the amine groups was achieved, in the case of enantiopure
      compounds. Interestingly, racemates led to both racemic conglomerate and solid
      solution formation, with a concomitant loss of positional and orientational
      control of the amino groups as a result.

PMID- 22132744
TI  - Oligoamine analogues in combination with 2-difluoromethylornithine
      synergistically induce re-expression of aberrantly silenced tumour-suppressor
      genes.
AB  - Epigenetic gene silencing is an important mechanism in the initiation and
      progression of cancer. Abnormal DNA CpG island hypermethylation and histone
      modifications are involved in aberrant silencing of tumour-suppressor genes. LSD1
      (lysine-specific demethylase 1) was the first enzyme identified to specifically
      demethylate H3K4 (Lys(4) of histone H3). Methylated H3K4 is an important mark
      associated with transcriptional activation. The flavin adenine dinucleotide
      binding amine oxidase domain of LSD1 is homologous with two polyamine oxidases,
      SMO (spermine oxidase) and APAO (N(1)-acetylpolyamine oxidase). We have
      demonstrated previously that long-chain polyamine analogues, the oligoamines, are
      inhibitors of LSD1. In the present paper we report the synergistic effects of
      specific oligoamines in combination with DFMO (2-difluoromethylornithine), an
      inhibitor of ornithine decarboxylase, in human colorectal cancer cells. DFMO
      treatment depletes natural polyamines and increases the uptake of exogenous
      polyamines. The combination of oligoamines and DFMO results in a synergistic re
      expression of aberrantly silenced tumour-suppressor genes, including SFRP2
      (secreted frizzled-related protein 2), which encodes a Wnt signalling pathway
      antagonist and plays an anti-tumorigenic role in colorectal cancer. The treatment
      induced re-expression of SFRP2 is associated with increased H3K4me2 (di-methyl
      H3K4) in the gene promoter. The combination of LSD1-inhibiting oligoamines and
      DFMO represents a novel approach to epigenetic therapy of cancer.

PMID- 22132746
TI  - Post mastectomy radiotherapy in one to three lymph node positive breast cancer.

PMID- 22132747
TI  - The relationship between the bladder volume and optimal treatment planning in
      definitive radiotherapy for localized prostate cancer.
AB  - BACKGROUND: There is no current consensus regarding the optimal bladder volumes
      in definitive radiotherapy for localized prostate cancer. The aim of this study
      was to clarify the relationship between the bladder volume and optimal treatment
      planning in radiotherapy for localized prostate cancer. MATERIAL AND METHODS: Two
      hundred and forty-three patients underwent definitive radiotherapy with helical
      tomotherapy for intermediate- and high-risk localized prostate cancer. The
      prescribed dose defined as 95% of the planning target volume (PTV) receiving ?
      100% of the prescription dose was 76 Gy in 38 fractions. The clinical target
      volume (CTV) was defined as the prostate with a 5-mm margin and 2 cm of the
      proximal seminal vesicle. The PTV was defined as the CTV with a 5-mm margin.
      Treatment plans were optimized to satisfy the dose constraints defined by in
      house protocols for PTV and organs at risk (rectum wall, bladder wall, sigmoid
      colon and small intestine). If all dose constraints were satisfied, the plan was
      defined as an optimal plan (OP). RESULTS: An OP was achieved with 203 patients
      (84%). Mean bladder volume (+/- 1 SD) was 266 ml (+/- 130 ml) among those with an
      OP and 214 ml (+/-130 ml) among those without an OP (p = 0.02). Logistic
      regression analysis also showed that bladder volumes below 150 ml decreased the
      possibility of achieving an OP. However, the percentage of patients with an OP
      showed a plateau effect at bladder volumes above 150 ml. CONCLUSIONS: Bladder
      volume is a significant factor affecting OP rates. However, our results suggest
      that bladder volumes exceeding 150 ml may not help meet planning dose
      constraints.

PMID- 22132748
TI  - Menopausal symptoms are associated with subclinical atherosclerosis in healthy
      recently postmenopausal women.
AB  - OBJECTIVES: To determine whether menopausal symptoms are associated with changes
      in arterial structure and function in healthy, recently postmenopausal women.
      METHODS: One hundred and ten postmenopausal women aged 45-55 years were included
      in the present cross-sectional study. Menopausal symptoms were recorded by the
      Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids,
      glucose, insulin, sex and thyroid hormones were determined in each individual.
      Arterial structure, function and stiffness were assessed by intima-media
      thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively.
      RESULTS: Women with moderate to severe hot flushes had increased IMT compared to
      women with no or mild hot flushes (IMT in women with no hot flushes 0.61+/-0.08
      mm, IMT in women with mild hot flushes 0.62+/-0.11 mm, IMT in women with moderate
      to severe hot flushes 0.67+/-0.11 mm; p = 0.034). This difference was independent
      of cardiovascular risk factors like age, menopausal age, smoking, blood pressure,
      adiposity, lipid levels, insulin resistance or hormone levels. No association was
      detected between psychological or psychosomatic symptoms and arterial indices.
      Furthermore, menopausal symptoms were not associated with serum sex steroids or
      thyroid hormone levels. CONCLUSIONS: Carotid IMT, a surrogate marker of
      subclinical atherosclerosis and cardiovascular risk, was found to be increased in
      women with vasomotor symptoms as compared to asymptomatic women. This association
      was independent of cardiovascular risk factors or endogenous hormone levels. It
      remains to be elucidated whether the presence of menopausal symptoms is an
      additional cardiovascular risk factor requiring preventive intervention.

PMID- 22132749
TI  - The value of pre-donation pulse assessment for apheresis donors.
AB  - OBJECTIVES: During apheresis, donors have up to 6 . 5 L of blood processed and
      receive citrated plasma during the return cycle. It is of concern that a donor
      with an unrecognised significant cardiac abnormality might therefore be put at
      further risk during apheresis. BACKGROUND: Apheresis donors with cardiac
      abnormalities may be at increased risk of severe adverse reactions as a result of
      repeated volume loss or the adverse effect of citrate anticoagulant on cardiac
      contractility as the result of reduction in ionised calcium. An abnormal rate or
      rhythm may indicate a cardiac abnormality. METHODS: At two donation centres
      between May 2001 and April 2009, the pulse rate and rhythm of every donor was
      measured before each apheresis procedure they underwent. Donors with a pulse rate
      outside the range 50-100 beats per minute and/or pulse irregularity were deferred
      from donation and referred to their general practitioner (GP). RESULTS: Data from
      3945 apheresis donors (3874 platelet donors, 71 plasma donors, 3595 males, 350
      females) were reviewed. Two hundred thirty-eight donors (6%) were identified as
      having abnormal pulses and were referred to their GP. Eighty-one donors had
      bradycardia, 16 had tachycardia and 141 had an irregular pulse. Fifteen of the
      3945 donors (0 . 4%) were found to have significant cardiac disease and withdrawn
      from the donor panel. CONCLUSIONS: By simple monitoring, donors who may be at
      increased risk from the apheresis procedure can be identified. By performing pre
      donation pulse assessment of all apheresis donors, we fulfil our medicolegal duty
      by not putting donors at avoidable risk.

PMID- 22132750
TI  - Meetings-the good, the bad, and the ugly.
AB  - Much has been written about how to facilitate an effective meeting, but
      apparently not every meeting facilitator has read the literature because every
      occupational health nurse has endured a "bad" meeting. Individuals who chair
      meetings have a responsibility to create meetings that are worthwhile to the
      attendees; attendees have a responsibility to be prepared for meetings so
      meetings are productive. This article reviews key meeting strategies, providing
      readers with ways to improve meetings they attend or facilitate.

PMID- 22132751
TI  - Invisible pollution: the impact of pharmaceuticals in the water supply.
AB  - During the past decade, interest in the public and environmental health effects
      of trace levels of pharmaceuticals and personal care products in the water supply
      has evolved. Although most pharmaceuticals are tested for human safety and
      efficacy prior to marketing and distribution, the potential for adverse effects
      in nontarget populations exposed to minute environmental medication doses has not
      been established. Several recent studies have demonstrated adverse effects from
      longstanding, low-dose exposures in both aquatic and terrestrial wildlife,
      although human toxicity related to trace levels of pharmaceuticals in the water
      supply remains unknown. This article provides a brief overview of the routes
      through which pharmaceuticals are introduced into the environment; a description
      of the effects of longstanding, low-dose exposures in aquatic and terrestrial
      animals, including human health effects; an update on the current regulations and
      solutions regarding pharmaceutical disposal practices; and a discussion of
      implications for reducing pharmaceuticals in the environment for occupational
      health nurses and other allied health professionals.

PMID- 22132753
TI  - Working at high altitude.
AB  - High altitude is not just an issue for mountain climbers. Elevation can have
      implications for employees ranging from laborers to office workers to scientists.
      Awareness is key to effective management.

PMID- 22132754
TI  - Phosphatidylinositol 3-kinase pathway activation in breast cancer brain
      metastases.
AB  - INTRODUCTION: Activation status of the phosphatidylinositol 3-kinase (PI3K)
      pathway in breast cancer brain metastases (BCBMs) is largely unknown. We examined
      expression of phospho(p)-AKT, p-S6, and phosphatase and tensin homologue (PTEN)
      in BCBMs and their implications for overall survival (OS) and survival after
      BCBMs. Secondary analyses included PI3K pathway activation status and
      associations with time to distant recurrence (TTDR) and time to BCBMs. Similar
      analyses were also conducted among the subset of patients with triple-negative
      BCBMs. METHODS: p-AKT, p-S6, and PTEN expression was assessed with
      immunohistochemistry in 52 BCBMs and 12 matched primary BCs. Subtypes were
      defined as hormone receptor (HR)+/HER2-, HER2+, and triple-negative (TNBC).
      Survival analyses were performed by using a Cox model, and survival curves were
      estimated with the Kaplan-Meier method. RESULTS: Expression of p-AKT and p-S6 and
      lack of PTEN (PTEN-) was observed in 75%, 69%, and 25% of BCBMs. Concordance
      between primary BCs and matched BCBMs was 67% for p-AKT, 58% for p-S6, and 83%
      for PTEN. PTEN- was more common in TNBC compared with HR+/HER2- and HER2+.
      Expression of p-AKT, p-S6, and PTEN- was not associated with OS or survival after
      BCBMs (all, P > 0.06). Interestingly, among all patients, PTEN- correlated with
      shorter time to distant and brain recurrence. Among patients with TNBC, PTEN- in
      BCBMs was associated with poorer overall survival. CONCLUSIONS: The PI3K pathway
      is active in most BCBMs regardless of subtype. Inhibition of this pathway
      represents a promising therapeutic strategy for patients with BCBMs, a group of
      patients with poor prognosis and limited systemic therapeutic options. Although
      expression of the PI3K pathway did not correlate with OS and survival after BCBM,
      PTEN- association with time to recurrence and OS (among patients with TNBC) is
      worthy of further study.

PMID- 22132755
TI  - The effectiveness of moxibustion for the treatment of functional constipation: a
      randomized, sham-controlled, patient blinded, pilot clinical trial.
AB  - BACKGROUND: Moxibustion is an ancient traditional medicine using burning mugworts
      to stimulate acupuncture points. The aim of this study was to investigate the
      safety and efficacy of moxibustion for the treatment of constipation using a
      randomized, sham-controlled, participant-blinded, pilot trial. METHODS: Twenty
      six participants (identified with either qi (vital energy) deficiency or qi
      excess syndrome) were randomly divided into either a moxibustion or sham group.
      Participants were treated with real or sham moxibustion at 4 acupuncture points,
      ST23 and ST27, bilaterally, 3 times per week for four weeks. The primary outcome
      was the frequency of defecations; secondary outcomes were the Bristol stool form
      scale (BSS) and the constipation assessment scale (CAS). RESULTS: Of the 26
      participants that were randomized, 24 completed the study. Defecation frequency,
      BSS, and CAS showed no difference between the moxibustion and sham groups. The
      differences were -0.25 (95% CI: -2.08, 1.58, p = 0.78), -1.22 (95% CI: -2.7,
      0.26, p = 0.1), 0.91 (95% CI: -1.46, 3.28, p = 0.44) in defecation frequency,
      BSS, CAS, respectively. The defecation frequency increased from an average of 3.3
      to 4.6 times per week in the moxibustion group (1.5[-0.5, 2], p = 0.06) and from
      2.7 to 3.7 stools per week in the sham group (1[-1, 2], p = 0.15) after four
      weeks of treatment. The difference between participants with a deficiency or an
      excess syndrome, determined based on assessment of sweat, facial features, pain,
      body energy, and pulse type, was significant in only defecation frequency. The
      difference was 3.3 (95% CI: 0.41, 6.19, p = 0.03). CONCLUSION: Moxibustion
      treatment appears safe, but showed no positive effect on constipation. The
      effectiveness of moxibustion treatment may depend on the syndrome pattern, and
      further long-term studies with a larger number of subjects are warranted. TRIAL
      REGISTRATION: Clinical Research Information Service, KCT0000168.

PMID- 22132756
TI  - Assembly and proteolytic processing of mycobacterial ClpP1 and ClpP2.
AB  - BACKGROUND: Caseinolytic proteases (ClpPs) are barrel-shaped self
      compartmentalized peptidases involved in eliminating damaged or short-lived
      regulatory proteins. The Mycobacterium tuberculosis (MTB) genome contains two
      genes coding for putative ClpPs, ClpP1 and ClpP2 respectively, that are likely to
      play a role in the virulence of the bacterium. RESULTS: We report the first
      biochemical characterization of ClpP1 and ClpP2 peptidases from MTB. Both
      proteins were produced and purified in Escherichia coli. Use of fluorogenic model
      peptides of diverse specificities failed to show peptidase activity with
      recombinant mycobacterial ClpP1 or ClpP2. However, we found that ClpP1 had a
      proteolytic activity responsible for its own cleavage after the Arg8 residue and
      cleavage of ClpP2 after the Ala12 residue. In addition, we showed that the
      absence of any peptidase activity toward model peptides was not due to an
      obstruction of the entry pore by the N-terminal flexible extremity of the
      proteins, nor to an absolute requirement for the ClpX or ClpC ATPase complex.
      Finally, we also found that removing the putative propeptides of ClpP1 and ClpP2
      did not result in cleavage of model peptides. We have also shown that recombinant
      ClpP1 and ClpP2 do not assemble in the conventional functional tetradecameric
      form but in lower order oligomeric species ranging from monomers to heptamers.
      The concomitant presence of both ClpP1 and ClpP2 did not result in tetradecameric
      assembly. Deleting the amino-terminal extremity of ClpP1 and ClpP2 (the putative
      propeptide or entry gate) promoted the assembly in higher order oligomeric
      species, suggesting that the flexible N-terminal extremity of mycobacterial ClpPs
      participated in the destabilization of interaction between heptamers. CONCLUSION:
      Despite the conservation of a Ser protease catalytic triad in their primary
      sequences, mycobacterial ClpP1 and ClpP2 do not have conventional peptidase
      activity toward peptide models and display an unusual mechanism of self-assembly.
      Therefore, the mechanism underlying their peptidase and proteolytic activities
      might differ from that of other ClpP proteolytic complexes.

PMID- 22132757
TI  - Subclass-specific localization and trafficking of Arabidopsis p24 proteins in the
      ER-Golgi interface.
AB  - We describe a comprehensive analysis of the subcellular localization and in vivo
      trafficking of Arabidopsis p24 proteins. In Arabidopsis, there are 11 p24
      proteins, which fall into only delta and beta subfamilies. Interestingly, the
      delta subfamily of p24 proteins in Arabidopsis is elaborated spectacularly in
      evolution, which can be grouped into two subclasses: p24delta1 and p24delta2. We
      found that, although all p24delta proteins possess classic COPII/COPI binding
      motifs in their cytosolic C-termini, p24delta1 proteins are localized to the
      endoplasmic reticulum (ER), p24delta2 proteins are localized to both ER and
      Golgi. Two p24beta proteins reside largely in Golgi. Similar to Atp24 (termed
      p24delta1c in this study), p24delta2d also cycles between the ER and Golgi.
      Interestingly, coexpression with p24beta1 could retain p24delta2d, but not
      p24delta1d in Golgi. We revealed that the lumenal coiled-coil domain of
      p24delta2d is required for its steady-state localization in Golgi, probably
      through its interaction with p24beta1. In p24beta1, there is no classic COPII or
      COPI binding motif in its C-terminus. However, the protein also cycles between
      the ER and Golgi. We found that a conserved RV motif located at the extreme end
      of the C-terminus of p24beta1 plays an important role in its Golgi target.

PMID- 22132758
TI  - The contribution of traditional healers' clinics to public health care system in
      Addis Ababa, Ethiopia: a cross-sectional study.
AB  - BACKGROUND: Ethiopian people have been using traditional medicine since time
      immemorial with 80% of its population dependent on traditional medicines.
      However, the documentation of traditional healers' clinics contribution to modern
      public health system in cosmopolitan cities is scanty. Studies conducted so far
      are limited and focused on the perceptions and practices of modern and
      traditional health practitioners about traditional medicine. Thus, a cross
      sectional study was conducted from February to May 2010 to assess the
      contribution of traditional healers' clinics to public health care system in
      Addis Ababa. MATERIALS AND METHODS: Ten traditional healers who were willing to
      participate in the study and 306 patients who were visiting these traditional
      healers' clinics were interviewed using two types of semi-structured
      questionnaires. Data were summarized using percentages, tables and bar chart.
      RESULTS: The diseases mostly treated by traditional healers were wound,
      inflammation, herpes zoster, hemorrhoids, fracture, paralysis, back-pain, liver
      diseases, cancer and eczema. This study showed that traditional healers' clinics
      considerably contribute to public health care in Addis Ababa. Fifty two percent
      of patients reported that traditional healers' clinics were their first choice
      when they faced health problems. The reasons for visiting these clinics were 175
      (57.2%) efficacy, 109 (35.6%) dissatisfaction with modern medicine, 10 (3.3%)
      dissatisfaction with modern medicine and efficacy, 6 (2.0%) cost and 6 (2.0%)
      dissatisfaction and cost. Females (55.2%), young age (20-40 years, 65.0%), never
      married (56.9%), orthodox (73.9%), Amhara (52.3%), educational status above grade
      12 (34.6%) and government employees (29.4%) were frequent visitors. Healers
      reported that there was no form of cooperation with modern health professionals.
      The reasons were lack of motivation to collaborate and communicate with modern
      health service workers. Family based apprenticeship was the sources of knowledge
      for majority of the healers. CONCLUSIONS: The study conducted showed that for the
      majority of patients interviewed traditional healers' clinics were one of the
      options to solve their health problems that indicated the considerable
      contribution of these clinics to the public health care system in Addis Ababa.
      Nevertheless, in this study the contribution of traditional healers' clinics to
      the public health system would have been better shown if individuals who are not
      users of the traditional healers' clinics were included in the interview.
      However, the study might be useful as a base line data for future evaluation of
      the significance of traditional healers' clinics for public health system and the
      services rendered in these clinics.

PMID- 22132759
TI  - Isolation and structure elucidation of two new cytotoxic metabolites from red
      yeast rice.
AB  - In this study, 10 already described secondary metabolites and 2 unknown
      metabolites were identified in an extract of Monascus purpureus by high
      performance liquid chromatography-diode array detection. The unknown metabolites
      were isolated and their chemical structures were elucidated. The new metabolites
      possess the molecular formulas C(21)H(27)NO(4) and C(23)H(31)NO(4). They were
      named monascopyridines E and F due to their pyridine backbone. The cytotoxicity
      of the new compounds was studied using immortalised human kidney epithelial cells
      displaying IC(50) values in the micromolar range.

PMID- 22132761
TI  - Protein isoaspartate methyltransferase-mediated 18O-labeling of isoaspartic acid
      for mass spectrometry analysis.
AB  - Arising from spontaneous aspartic acid (Asp) isomerization or asparagine (Asn)
      deamidation, isoaspartic acid (isoAsp, isoD, or beta-Asp) is a ubiquitous
      nonenzymatic modification of proteins and peptides. Because there is no mass
      difference between isoaspartyl and aspartyl species, sensitive and specific
      detection of isoAsp, particularly in complex samples, remains challenging. Here
      we report a novel assay for Asp isomerization by isotopic labeling with (18)O via
      a two-step process: the isoAsp peptide is first specifically methylated by
      protein isoaspartate methyltransferase (PIMT, EC 2.1.1.77) to the corresponding
      methyl ester, which is subsequently hydrolyzed in (18)O-water to regenerate
      isoAsp. The specific replacement of (16)O with (18)O at isoAsp leads to a mass
      shift of 2 Da, which can be automatically and unambiguously recognized using
      standard mass spectrometry, such as collision-induced dissociation (CID), and
      data analysis algorithms. Detection and site identification of several isoAsp
      peptides in a monoclonal antibody and the beta-delta sleep-inducing peptide
      (DSIP) are demonstrated.

PMID- 22132760
TI  - Feasibility and efficacy of a multidisciplinary health care programme for
      patients with knee osteoarthritis.
AB  - OBJECTIVES: To examine the feasibility and efficacy of a multidisciplinary health
      care programme for patients with knee OA. METHODS: A 12-month follow-up care
      programme for knee OA, based on clinical evidence and expert opinion was
      implemented in primary care settings. It included recommendations on diagnosis,
      management and follow-up. Consecutive patients with knee OA and pain were
      included, classified into mild (21-39 score), moderate (40-69 score), severe
      disease (70-100 score) in WOMAC pain subscale, and managed according to the
      programme. Data were recorded using electronic devices or internet at each visit.
      Primary end points were: OMERACT-OARSI responder criteria; 70% compliance rate of
      the recommendations. RESULTS: We included 226 patients, 75% women, mean age 63
      years, mean disease duration of 2.4 years, 76% reported Kellgren-Lawrence grade 3
      4, and were classified as mild: 17%, moderate: 54% and severe disease: 29%. At
      the end of the study, 78% of patients achieved pain relief of >= 20 points in the
      WOMAC pain subscale, and 80% OMERACT-OARSI response criteria. Almost 90% of
      physicians followed the recommendations. WOMAC and SF-36 subscales/dimensions
      improved (p<0.050), 14% remained classified as moderate or severe disease, 85% of
      patients attended the exercise training course, and more than 80% of patients and
      professionals were satisfied with the programme. Compared to usual care the
      programme seems to use fewer resources. CONCLUSIONS: The implementation of
      multidisciplinary health care programmes could be very effective and viable for
      the management of knee OA, could increase patients' and health professional's
      satisfaction, and optimise health care resources use.

PMID- 22132762
TI  - Case of allergy due to hydrolyzed wheat proteins in commercial boiled pork.

PMID- 22132763
TI  - A historical perspective on breast cancer activism in the United States: from
      education and support to partnership in scientific research.
AB  - Breast cancer remained a hidden disease among women in the United States until
      the 20th century. It was initially brought into the open with public revelations
      from individual women, which was followed by the development of support groups
      and ultimately the formation of political activist groups with various
      priorities. Those concerned with toxic environmental exposures as a potential
      cause of breast cancer organized, demonstrated, and lobbied for research funding
      and eventually became partners in the research that arose from their efforts. One
      representative example was the Breast Cancer and Environment Research Centers
      (BCERC) Project (2003-2010), supported by the National Institute of Environmental
      Health Sciences (NIEHS) and the National Cancer Institute (NCI). The BCERC
      embedded a Community Outreach and Translational Core into its formal
      organizational infrastructure to ensure advocate involvement in the standing
      scientific subcommittees of BCERC, the first project funded by NIEHS and NCI to
      do so. The formal integration of advocates as partners in scientific studies
      focused on breast cancer is embedded in a rich history of action on the part of
      many courageous women. This article describes the historical evolution of breast
      cancer activism in the United States, which provided a critical foundation for
      the formation of BCERC. This description is followed by a discussion of BCERC as
      an example of the transdisciplinary research model, a paradigm that strives for
      inclusion of multiple stakeholders and increased interaction between scientists
      from a wide spectrum of disciplines, advocates, and lay audiences in order to
      more effectively conduct critical research and to translate and disseminate its
      findings.

PMID- 22132764
TI  - Electronic, spectroscopic, and ion-sensing properties of a dehydro[m]pyrido[14]-
      and [15]annulene isomer library.
AB  - An isomeric series of dehydro[m]pyrido[n]annulenes incorporating strained 1,4
      buta-1,3-diyne units have been synthesized, where m = 2, n = 14 (1a-d); m = 2, n
      = 15 (2a,b); and m = 3, n = 15 (3). The number of pyridine rings and annulene
      ring pi-electrons are denoted by m and n, respectively. The X-ray crystal
      structures of 1b and 1c confirmed their cyclic formulation. All macrocycles were
      found to be luminescent chromophores with differing isomer-dependent proton and
      metal ion-sensory emission responses, which appear collectively as analyte
      specific color patterns. Within the series studied, 1a was singular in displaying
      the highest luminescence quantum yield and sharing the strongest emission energy
      and molar absorption changes upon protonation and Hg(II) binding. Spectroscopic
      and electrochemical results were supported by density functional theory
      calculations in showing 1a, 2a, and 3 to be low bandgap materials with lowest
      unoccupied molecular orbitals delocalized over the 1,4-di(pyridin-4-yl)buta-1,3
      diyne bridges that provide a pathway for electronic communication between the
      nitrogens. Overall, the investigations suggest that 1a, 2a, and 3 would be
      excellent ligands for the construction of novel conjugated hybrid
      metallosupramolecular nanostructures, polymers, and ion-sensory systems.

PMID- 22132765
TI  - The BASES expert statement on exercise, immunity, and infection.
AB  - An individual's level of physical activity influences their risk of infection,
      most likely by affecting immune function. Regular moderate exercise reduces the
      risk of infection compared with a sedentary lifestyle, but very prolonged bouts
      of exercise and periods of intensified training are associated with an increased
      risk of infection. There are several lifestyle, nutritional, and training
      strategies that can be adopted to limit the extent of exercise-induced
      immunodepression and minimize the risk of infection. This expert statement
      provides a background summarizing the evidence together with extensive
      conclusions and practical guidelines.

PMID- 22132766
TI  - Reutilization of mango byproducts: study of the effect of extraction solvent and
      temperature on their antioxidant properties.
AB  - Mango biowastes, obtained after processing, contain large amounts of compounds
      with antioxidant activity that can be reused to reduce their environmental
      impact. The present study evaluates the effect of solvent (methanol, ethanol,
      acetone, water, methanol:water [1:1], ethanol:water [1:1], and acetone:water
      [1:1]), and temperature (25, 50, and 75  degrees C) on the efficiency of the
      extraction of antioxidants from mango peel and seed. Among the factors optimized,
      extraction solvent was the most important. The solvents that best obtained
      extracts with high antioxidant capacity were methanol, methanol:water,
      ethanol:water, and acetone:water (beta-carotene test, antioxidant activity
      coefficient 173 to 926; thiobarbituric acid reactive substances test, inhibition
      ratio 15% to 89%; 2,2'-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid
      ABTS(.+); and 2,2-diphenyl-1-picrylhydrazyl DPPH. scavenging, 7 to 22 and 8 to 28
      g trolox equivalent antioxidant capacity [TE] per 100 g mango biowaste on a dry
      matter basis [DW]). Similarly, the flavonoid (0.21 to 1.4 g (+)-catechin
      equivalents per 100 g DW), tannin (3.8 to 14 g tannic acid equivalents per 100 g
      DW), and proanthocyanidin (0.23 to 7.8 g leucoanthocyanidin equivalents per 100 g
      DW) content was highest in the peel extracts obtained with methanol,
      ethanol:water, or acetone:water and in the seed extracts obtained with methanol
      or acetone:water. From the perspective of food security, it is advisable to
      choose ethanol (which also has a notable antioxidant content), ethanol:water, or
      acetone:water, as they are all solvents that can be used in compliance with good
      manufacturing practice. In general, increasing temperature improves the capacity
      of the extracts obtained from mango peel and seed to inhibit lipid peroxidation;
      however, its effect on the extraction of phytochemical compounds or on the
      capacity of the extracts to scavenge free radicals was negligible in comparison
      to that of the solvent. PRACTICAL APPLICATION: There are many antioxidant
      compounds in mango peel and seed, and they could be used as a natural and very
      inexpensive alternative to synthetic food additives. However, the conditions in
      which the antioxidants are extracted must be optimized. This work proves that
      conditions such as extraction solvent or temperature have a crucial impact on
      obtaining extracts rich in antioxidants from mango biowastes.

PMID- 22132768
TI  - New paradigm or old distance to target?

PMID- 22132769
TI  - Allosteric antibody inhibition of human hepsin protease.
AB  - Hepsin is a type II transmembrane serine protease that is expressed in several
      human tissues. Overexpression of hepsin has been found to correlate with tumour
      progression and metastasis, which is so far best studied for prostate cancer,
      where more than 90% of such tumours show this characteristic. To enable improved
      future patient treatment, we have developed a monoclonal humanized antibody that
      selectively inhibits human hepsin and does not inhibit other related proteases.
      We found that our antibody, hH35, potently inhibits hepsin enzymatic activity at
      nanomolar concentrations. Kinetic characterization revealed non-linear, slow,
      tight-binding inhibition. This correlates with the crystal structure we obtained
      for the human hepsin-hH35 antibody Fab fragment complex, which showed that the
      antibody binds hepsin around alpha3-helix, located far from the active centre.
      The unique allosteric mode of inhibition of hH35 is distinct from the recently
      described HGFA (hepatocyte growth factor activator) allosteric antibody
      inhibition. We further explain how a small change in the antibody design induces
      dramatic structural rearrangements in the hepsin antigen upon binding, leading to
      complete enzyme inactivation.

PMID- 22132770
TI  - Pharmacokinetics of concurrently administered intravenous lidocaine and flunixin
      in healthy horses.

PMID- 22132771
TI  - Predictors of intentions to use hormone replacement therapy in clinical
      postmenopausal women.
AB  - OBJECTIVES: To investigate the contribution of components of the Health Beliefs
      Model (perceived susceptibility, perceived severity, health motivation, perceived
      risk and benefits of hormone replacement therapy (HRT) use), sociodemographic
      variables (age, duration of postmenopause, hysterectomy and social class) and
      psychological stress to intentions to use HRT for the first time. METHODS: A
      quasi-experimental design was used to recruit a clinical sample of 180
      postmenopausal women, attending a menopause clinic, with a mean age of 50.74
      years (standard deviation 4.75 years). Data were collected using self-report
      questionnaires. A regression analysis was carried out to establish what predicts
      intentions to use HRT in this sample; sociodemographic variables were entered in
      the first step of the regression, followed by health motivation and perceived
      stress in step two, the third step involved the addition of perceived severity
      measures, and in the final step susceptibility and perceived risks and benefits
      were added. RESULTS: The main predictor of intentions to use HRT, after
      controlling for all other variables, was the belief that the benefits outweigh
      the risks associated with taking HRT. CONCLUSIONS: This information should be
      used to develop interventions and health awareness materials about HRT in
      clinical postmenopausal women.

PMID- 22132772
TI  - Case report of a haemovigilance investigation using phylogenetic analysis of HIV
      1 in Brazil.
AB  - OBJECTIVES: The aim of this work is to provide the first report of a transfusion
      acquired HIV-1 infection and to verify transmission from the donor to the
      recipients using phylogenetic analysis of HIV-1 DNA sequences in a Brazilian
      blood bank. BACKGROUND: Although haemovigilance procedures based on phylogenetic
      analysis of HIV have been reported in several countries, this type of study has
      yet to be conducted in Latin America. MATERIALS AND METHODS: Upon identifying a
      HIV-1-positive repeat blood donor by enzyme immunoassay (EIA) blood screening,
      all recipients of the donor's previous donation were identified and tested for
      HIV-1 by EIA, nucleic acid amplification test and HIV-1 DNA sequencing and
      phylogenetic analysis. RESULTS: One of the recipients tested positive for HIV-1.
      The phylogenetic analysis showed a high genetic similarity among the viruses,
      thus supporting the hypothesis of transmission from the donor to the recipient.
      CONCLUSIONS: Phylogenetic analysis of HIV-1 DNA sequences has been a decisive
      tool in verifying suspected transmission of the virus from blood donor to
      recipient in Brazil.

PMID- 22132773
TI  - Saxagliptin for the treatment of type 2 diabetes mellitus: focus on recent
      studies.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs
      that improve glycemic control without causing weight gain or increasing
      hypoglycemic risk in patients with type 2 diabetes (T2DM). The efficacy and
      tolerability of saxagliptin, a once-daily DPP-4 inhibitor, administered as
      monotherapy, as add-on therapy to metformin, a sulfonylurea, or a
      thiazolidinedione, and as initial combination therapy with metformin, was
      demonstrated in pivotal 24-week clinical trials. Additional information about the
      clinical profile of saxagliptin was recently obtained from extension studies,
      head-to-head clinical trials, and post-hoc analyses. In extension studies, the
      efficacy and tolerability of add-on saxagliptin and initial saxagliptin-plus
      metformin therapy were maintained for up to 102 weeks. Saxagliptin plus metformin
      was shown to be non-inferior to glipizide plus metformin in lowering glycated
      hemoglobin from base-line, with reduced body-weight and lower hypoglycemic risk.
      Post-hoc analyses indicate that the clinical benefits of saxagliptin extend
      across demographic subgroups and special populations. A meta-analysis found no
      evidence for increased cardiovascular risk in T2DM patients exposed to
      saxagliptin for > 1 year. On the basis of this clinical profile, saxagliptin is
      an attractive option for initial and add-on therapy for T2DM patients with
      inadequate glycemic control.

PMID- 22132774
TI  - Short-term effects of liraglutide on visceral fat adiposity, appetite, and food
      preference: a pilot study of obese Japanese patients with type 2 diabetes.
AB  - BACKGROUND: To examine the effects of liraglutide, a glucagon-like peptide-1 (GLP
      1) analogue, on visceral fat adiposity, appetite, food preference, and biomarkers
      of cardiovascular system in Japanese patients with type 2 diabetes. METHODS: The
      study subjects were 20 inpatients with type 2 diabetes treated with liraglutide
      [age; 61.2 +/- 14.0 years, duration of diabetes; 16.9 +/- 6.6 years, glycated
      hemoglobin (HbA1c); 9.1 +/- 1.2%, body mass index (BMI); 28.3 +/- 5.2 kg/m(2),
      mean +/- SD]. After improvement in glycemic control by insulin or oral glucose
      lowering agents, patients were switched to liraglutide. We assessed the estimated
      visceral fat area (eVFA) by abdominal bioelectrical impedance analysis, glycemic
      control by the 75-g oral glucose tolerance test (OGTT) and eating behavior by the
      Japan Society for the Study of Obesity questionnaire. RESULTS: Treatment with
      liraglutide (dose range: 0.3 to 0.9 mg/day) for 20.0 +/- 6.4 days significantly
      reduced waist circumference, waist/hip ratio, eVFA. It also significantly
      improved the scores of eating behavior, food preference and the urge for fat
      intake and tended to reduce scores for sense of hunger. Liraglutide increased
      serum C-peptide immunoreactivity and disposition index. CONCLUSIONS: Short-term
      treatment with liraglutide improved visceral fat adiposity, appetite, food
      preference and the urge for fat intake in obese Japanese patients with type 2
      diabetes.

PMID- 22132775
TI  - Lack of sufficiently strong informative features limits the potential of gene
      expression analysis as predictive tool for many clinical classification problems.
AB  - BACKGROUND: Our goal was to examine how various aspects of a gene signature
      influence the success of developing multi-gene prediction models. We inserted
      gene signatures into three real data sets by altering the expression level of
      existing probe sets. We varied the number of probe sets perturbed (signature
      size), the fold increase of mean probe set expression in perturbed compared to
      unperturbed data (signature strength) and the number of samples perturbed.
      Prediction models were trained to identify which cases had been perturbed.
      Performance was estimated using Monte-Carlo cross validation. RESULTS: Signature
      strength had the greatest influence on predictor performance. It was possible to
      develop almost perfect predictors with as few as 10 features if the fold
      difference in mean expression values were > 2 even when the spiked samples
      represented 10% of all samples. We also assessed the gene signature set size and
      strength for 9 real clinical prediction problems in six different breast cancer
      data sets. CONCLUSIONS: We found sufficiently large and strong predictive
      signatures only for distinguishing ER-positive from ER-negative cancers, there
      were no strong signatures for more subtle prediction problems. Current
      statistical methods efficiently identify highly informative features in gene
      expression data if such features exist and accurate models can be built with as
      few as 10 highly informative features. Features can be considered highly
      informative if at least 2-fold expression difference exists between comparison
      groups but such features do not appear to be common for many clinically relevant
      prediction problems in human data sets.

PMID- 22132777
TI  - Universal endogenous gene controls for bisulphite conversion in analysis of plant
      DNA methylation.
AB  - Accurate analysis of DNA methylation by bisulphite sequencing depends on the
      complete conversion of all cytosines into uracil. Until now there has been no
      standard or universal gene identified as an endogenous control to monitor the
      conversion frequency in plants. Here, we report the development of PCR based
      assays for one nuclear gene IND (INDEHISCENT) and two mitochondrial genes, NAD
      (NICOTINAMIDE ADENINE DINUCLEOTIDE) and ATP1 (ATPase SUBUNIT 1). We demonstrated
      their efficacy as bisulphite conversion controls in Brassica and other plant
      taxa. The target regions amplified by four primer pairs were found to be
      consistently free from DNA methylation. Primer pairs for IND.a and NAD were
      effective within Brassica species, whereas two primer pairs for ATP1 provided
      reliable controls across a representative range of dicot and monocot angiosperm
      species. These primer sets may therefore be adopted as controls in plant
      methylation analysis for a wide range of studies.

PMID- 22132776
TI  - Live-cell assays to identify regulators of ER-to-Golgi trafficking.
AB  - We applied fluorescence microscopy-based quantitative assays to living cells to
      identify regulators of endoplasmic reticulum (ER)-to-Golgi trafficking and/or
      Golgi complex maintenance. We first validated an automated procedure to identify
      factors which influence Golgi-to-ER relocalization of GalT-CFP (beta1,4
      galactosyltransferase I-cyan fluorescent protein) after brefeldin A (BFA)
      addition and/or wash-out. We then tested 14 proteins that localize to the ER
      and/or Golgi complex when overexpressed for a role in ER-to-Golgi trafficking.
      Nine of them interfered with the rate of BFA-induced redistribution of GalT-CFP
      from the Golgi complex to the ER, six of them interfered with GalT-CFP
      redistribution from the ER to a juxtanuclear region (i.e. the Golgi complex)
      after BFA wash-out and six of them were positive effectors in both assays.
      Notably, our live-cell approach captures regulator function in ER-to-Golgi
      trafficking, which was missed in previous fixed cell assays, as well as assigns
      putative roles for other less characterized proteins. Moreover, we show that our
      assays can be extended to RNAi and chemical screens.

PMID- 22132778
TI  - Chitotriosidase levels in patients with severe endometriosis.
AB  - OBJECTIVE: To study the levels of chitotriosidase activity in the peritoneal
      fluid and the plasma of patients with severe endometriosis and control subjects.
      MATERIALS AND METHODS: Twenty-five women with laparoscopically and
      histopathologically confirmed endometriosis (study group) and 27 control patients
      who had undergone laparoscopic surgery were included. Peritoneal fluid and
      peripheral blood were obtained from all the patients before the surgery.
      Chitotriosidase activities were measured. RESULTS: Analysis of chitotriosidase
      activity in the peritoneal fluid of patients with endometriosis showed that there
      was no significant difference between endometriosis and control group,
      respectively (32.04 +/- 64.20 vs. 15.25 +/- 31.17 nmol/mL/h; p > 0.05). Analysis
      of chitotriosidase activity in plasma of patients with endometriosis showed
      significantly increased levels of chitotriosidase levels compared with the
      control group (74.81 +/- 60.54 vs. 14.10 +/- 26.17; p < 0.001), respectively.
      CONCLUSION: We found that the activity of chitotriosidase in plasma was
      statistically higher in severe endometriosis patients than women without
      endometriosis.

PMID- 22132780
TI  - Fractionation of carbon-based nanomaterials by anion-exchange HPLC.
AB  - A sample containing carbon nanoparticles was obtained starting with the soot
      generated during combustion of inexpensive paraffin oil in a flame. The
      complexity of the sample, however, required fractionation to isolate its
      components. Anion-exchange high-performance liquid chromatography (AE-HPLC) was
      used for the analysis and collection of soot-derived carbon nanoparticles. The
      fractionated species were monitored by ultraviolet (UV) absorption and laser
      induced photoluminescence detection, providing the chromatographic UV absorption
      and emission profiles of the separated sample. Chromatographic fractionation
      allowed for bulk measurements of electronic properties for individual fractions
      and further analysis via transmission electron microscopy (TEM). TEM of
      fractionated species showed a predominant size of about 4-5 nm diameter
      particulates. A general trend between photoluminescence and elution time was
      observed; the later eluting species in the chromatogram exhibited
      photoluminescence at longer wavelengths than the early eluting species. The AE
      HPLC approach can have an immediate impact on the analysis and fractionation of
      various other nanomaterials, demonstrated here by analyzing samples containing
      graphitic oxide nanoparticles.

PMID- 22132779
TI  - Magnetic resonance imaging of wrist and finger joints distinguishes secondary
      Sjogren's syndrome with rheumatoid arthritis from primary Sjogren's syndrome with
      articular manifestations.

PMID- 22132781
TI  - Propylthiouracil-induced antineutrophil cytoplasmic antibody positive vasculitis
      clinically mimicking pyoderma gangrenosum.

PMID- 22132782
TI  - Burrow plasticity in the deep-sea isopod Bathynomus doederleini (Crustacea:
      Isopoda: Cirolanidae).
AB  - We investigated whether the deep-sea isopod Bathynomus doederleini has the
      capacity to change burrow length in response to changes in environmental
      conditions. We observed burrowing behavior in individuals that were placed on
      substrates with either simple (ST) or complex (CT) surface topographies.
      Individuals in the ST group (N = 10) constructed seven burrows. The mean ratio of
      the burrow length to body length was 1.8. The individuals in the CT group (N =
      10) constructed eight burrows with a mean ratio of burrow length to body length
      of 2.5. Thus the burrows were significantly longer in the CT group. In addition,
      the isopods in the CT group often incorporated a chamber in the mid-section of
      the burrow. Our results may be used to infer the determinants of burrow
      morphology and speculate about the lifestyle of this species in the deep sea.

PMID- 22132783
TI  - Predominance of cross-predation between lateral morphs in a largemouth bass and a
      freshwater goby.
AB  - The predator-prey relationship between largemouth bass, Micropterus salmoides,
      and freshwater goby, Rhinogobius spp., in Lake Biwa, Japan, was examined with
      respect to their morphological antisymmetry (laterality). Largemouth bass and
      Rhinogobius gobies exhibited lateral dimorphism in the height of the mandible and
      the length of the dentary, respectively. Populations of both species were
      composed of both left-developed and right-developed individuals. Each predation
      event was categorized as either cross-predation (a predator caught prey of the
      opposite morph) or parallel-predation (a predator caught prey of the same morph).
      Stomach contents analysis revealed that cross-predation events predominated over
      parallel-predation. Annual sampling for eight years demonstrated that in both
      largemouth bass and Rhinogobius gobies, the ratio of right-developed individuals
      in the population fluctuated temporally around 0.5. As the predominance of cross
      predation was found in the relationship between the exotic largemouth bass and an
      endemic goby, the predominance may be caused by a kinematical interplay at each
      predation event.

PMID- 22132784
TI  - A cicada that ensures its fitness during climate warming by synchronizing its
      hatching time with the rainy season.
AB  - A shift in phenology due to climate change is associated with some recent changes
      in populations, as it can disrupt the synchrony between organisms' requirements
      and resource availability. This conceptual framework has been developed mostly in
      systems of trophic interactions. Many coincidental changes, however, are involved
      in trophic interactions, preventing us from describing the direct impact of
      phenological shifts on fitness consequences. Here we address the phenological
      relationship in a simple non-trophic interaction to document a causal process of
      a warming-driven fitness change in a cicada, Cryptotympana facialis, whose
      numbers increased dramatically in Osaka, Japan in the late 20th century. We show
      that synchrony of the rainy season and hatching time may have a substantial
      influence on hatching success, by 1) shifting the time of completion of embryonic
      development, and 2) supplying water at various intervals. We estimate the change
      in hatching time over the last eleven decades (1901-2009) based on meteorological
      records and the temperature-dependent rate of C. facialis embryogenesis. Our
      estimate shows that hatching had initially occurred after the rainy season, and
      that warming had advanced it into the rainy season in the late 20th century. The
      probability of hatching success was markedly variable, and often very low before
      this synchronization occurred, but became stably high thereafter. Our findings
      suggest that the stabilizing effect of this synchrony on fitness was
      indispensable to the recent population increase of C. facialis.

PMID- 22132785
TI  - Neuropeptide Y in tiger puffer (Takifugu rubripes): distribution, cloning,
      characterization, and mRNA expression responses to prandial condition.
AB  - Neuropeptide tyrosine (NPY) is a potent orexigenic neuropeptide implicated in
      feeding regulation in rodents. However, the involvement of NPY in feeding
      behavior has not well been studied in fish. Therefore, we investigated the role
      of NPY in food intake using a tiger puffer (Takifugu rubripes) model. We observed
      the distribution of NPY-like immunoreactivity in the brain. Neuronal cell bodies
      containing NPY were located in the telencephalon, hypothalamus, mesencephalon,
      and medulla oblongata, and their nerve fibers were also found throughout the
      brain. We cloned two cDNAs, encoding NPYa and NPYb orthologs, respectively, from
      the brain, and also confirmed two genes encoding these NPYs in the Takifugu
      genome database. We examined the distribution of these transcripts in the brain
      using real-time PCR. Levels of NPYa mRNA in the telencephalon, mesencephalon and
      hypothalamus were much higher than in the medulla oblongata and cerebellum,
      whereas levels of NPYb mRNA in the medulla oblongata were higher than in other
      regions. We also examined prandial effects on the expression level of these
      transcripts in the telencephalon and hypothalamus. NPYa mRNA levels in the
      hypothalamus, but not in the telencephalon, obtained from fish fasted for one
      week were higher than those in fish that had been fed normally. The level was
      decreased at 2 h after feeding. Levels of NPYb mRNA were not affected by prandial
      conditions. These results suggest that NPY is present throughout the brain, and
      that NPYa, but not NPYb, in the hypothalamus is involved in the feeding
      regulation in the tiger puffer.

PMID- 22132786
TI  - Genetic diversity of the Japanese wood pigeon, Columba janthina, endemic to
      islands of East Asia, estimated by newly developed microsatellite markers.
AB  - The Japanese wood pigeon Columba janthina is endemic to islands of East Asia and
      is listed as Near Threatened by the International Union for Conservation of
      Nature (IUCN). One subspecies, C. janthina nitens, in particular, is at the
      greatest risk of extinction due to its small population size. To reduce the
      extinction risk of C. janthina, it is important to understand the species'
      present genetic status and to develop an appropriate conservation plan based on
      genetic data. We developed seven new microsatellite markers for two subspecies of
      C. janthina: C. janthina janthina and C. janthina nitens. We also confirmed the
      cross-use of one microsatellite marker developed for Columba livia var.
      domestica. Seven loci were polymorphic in C. janthina janthina, while two loci
      were polymorphic in C. janthina nitens. Using the markers, we performed
      preliminary analysis of genetic diversity and genetic structure within each
      subspecies. The expected heterozygosity ranged from 0.00 to 0.64 in C. janthina
      janthina and from 0.00 to 0.08 in C. janthina nitens. Each subspecies and each
      population within C. janthina janthina had different allele frequencies. C.
      janthina nitens exhibited far lower genetic diversity than C. janthina janthina.
      Furthermore, C. janthina nitens appears to have experienced strong genetic drift
      from a common ancestral population, inferred by STRUCTURE analysis. The markers
      described here may be useful for investigating genetic diversity and genetic
      structure of C. janthina populations, and could be used to estimate appropriate
      evolutionary significant unit and to guide development of a captive breeding
      program based on genetic information.

PMID- 22132787
TI  - A circadian neuropeptide PDF in the honeybee, Apis mellifera: cDNA cloning and
      expression of mRNA.
AB  - Pigment-dispersing factor (PDF) is a pacemaker hormone regulating the locomotor
      rhythm in insects. In the present study, we cloned the cDNAs encoding the Apis
      PDF precursor protein, and found that there are at least seven different pdf
      mRNAs yielded by an alternative splicing site and five alternative
      polyadenylation sites in the 5'UTR and 3'UTR regions. The amino acid sequence of
      Apis PDF peptide has a characteristic novel amino acid residue, aspargine (Asn),
      at position 17. Quantitative real-time PCR of total and 5'UTR insertion-type pdf
      mRNAs revealed, for the first time, that the expression levels change in a
      circadian manner with a distinct trough at the beginning of night in LD
      conditions, and at the subjective night under DD conditions. In contrast, the
      expression level of 5'UTR deletion-type pdf mRNAs was about half of that of the
      insertion type, and the expression profile failed to show a circadian rhythm. As
      the expression profile of the total pdf mRNA exhibited a circadian rhythm,
      transcription regulated at the promoter region was supposed to be controlled by
      some of the clock components. Whole mount in situ hybridization revealed that 14
      lateral neurons at the frontal margin of the optic lobe express these mRNA
      isoforms. PDF expressing cells examined with a newly produced antibody raised
      against Apis PDF were also found to have a dense supply of axon terminals in the
      optic lobes and the central brain.

PMID- 22132788
TI  - Molecular phylogeny of Japanese Catocala moths based on nucleotide sequences of
      the mitochondrial ND5 gene.
AB  - Phylogenetic relationships of 31 Japanese Catocala species were analyzed based on
      the partial nucleotide sequences of the mitochondrial NADH dehydrogenase subunit
      5 (ND5) gene (762 bp). When several non-Catocala Noctuidae moths were designated
      as the outgroup, these Catocala species formed a monophyletic group. However,
      divergences between these Catocala species were very deep, and no close
      phylogenetic relationships were recognized among them except for that between the
      two recently separated species, C. xarippe and C. fulminea. The remote
      relationships implied for several pairs of species suggest that the color of the
      hindwings is a changeable characteristic, and does not reflect phylogenetic
      lineage. Continental specimens were analyzed in 20 of 31 Catocala species, and
      all of them showed a close relationship with their Japanese counterpart. However,
      the closeness of the nucleotide sequences between the Japanese and continental
      individuals of the same species varied from species to species, indicating that
      isolation between the Japanese and continental populations of these species
      occurred at many different times. The two analyzed species endemic to North
      America showed a close relationship with their morphologically inferred Japanese
      counterparts, indicating that the geographic separation and following speciation
      between these Eurasian and American species occurred much more recently compared
      with the speciation events among the Catocala species now found in Japan.

PMID- 22132789
TI  - Requirement of potassium for the action of anti-diuretic hormone (ADH) on frog
      skin.
AB  - The aim of the present study is to study whether the presence of K(+) in bathing
      media is required for the action of ADH to the ionic transport across the skin in
      the frog species Rana hexadactyla. lonic transport was measured as
      transepithelial potential difference (TEPD) and short circuit current (SCC) by
      using an indigenously developed computer based voltage-clamp technique. Addition
      of ADH (40 nM) on the serosal side significantly increased the TEPD and SCC with
      Normal Ringer (NR) on both sides. ADH had no effect subsequent to amiloride (100
      uM) pre-treatment, which confirmed the ADH-induced Na(+) transport. Chloride also
      has a significant role in the development of TEPD. To determine the role of K(+),
      Potassium-free Ringer (KFR) was placed on both sides; addition of ADH had no
      effect consequently. Further experiments were carried out to find out which side
      of K(+) was required for the action of ADH. There was a lack of ADH effect with
      apical NR and serosal KFR, demonstrating that serosal K(+) is essential to
      activate Na(+), K(+)- ATPase. Similarly, the ADH effect was lacking with apical
      KFR and serosal NR that was the novel finding of this study. Due to the
      concentration gradient, the K(+) was secreted from serosal side to apical side
      through barium (1 mM) blockable K(+) channel. This study provides evidence that
      serosal as well as apical K(+) are necessary for the action of ADH.

PMID- 22132790
TI  - A new species of the Fejervarya limnocharis complex from Japan (Anura,
      Dicroglossidae).
AB  - We describe a new species of dicroglossid frog of the Fejervarya limnocharis
      complex from western Honshu, Japan Mainland. The new species, Fejervarya
      kawamurai, is genetically closer to F. sakishimensis than to F. limnocharis. It
      differs from F. sakishimensis by smaller tympanum, head, forelimb, hindlimb,
      foot, and tibia lengths, all relative to snout-vent length, and from F.
      multistriata by relatively shorter forelimb, hindlimb, foot, and tibia. From F.
      limnocharis and F. iskandari, it is differentiated by relatively smaller
      forelimb, hindlimb, foot, and tibia lengths. Taxonomic problems of Fejervarya
      populations occurring in Central Ryukyus, continental China, and Taiwan are
      discussed.

PMID- 22132791
TI  - Taxonomic relationships among Turkish water frogs as revealed by phylogenetic
      analyses using mtDNA gene sequences.
AB  - We assessed taxonomic relationships among Turkish water frogs through estimation
      of phylogenetic relationships among 62 adult specimens from 44 distinct
      populations inhabiting seven main geographical regions of Turkey using 2897 bp
      sequences of the mitochondrial Cytb, 12S rRNA and 16S rRNA genes with equally
      weighted parsimony, likelihood, and Bayesian methods of inference. Monophyletic
      clade (Clade A) of the northwesternmost (Thrace) samples is identified as
      Pelophylax ridibundus. The other clade (Clade B) consisted of two monophyletic
      subclades. One of these contains specimens from southernmost populations that are
      regarded as an unnamed species. The other subclade consists of two lineages, of
      which one corresponds to P. caralitanus and another to P. bedriagae. Taxonomic
      relationships of these two species are discussed and recognition of P.
      caralitanus as a subspecies of P. bedriagae is proposed.

PMID- 22132792
TI  - Pre-cooling with ice slurry ingestion leads to similar run times to exhaustion in
      the heat as cold water immersion.
AB  - The purpose of this study was to compare the effects of pre-exercise ice slurry
      ingestion and cold water immersion on submaximal running time in the heat. On
      three separate occasions, eight males ran to exhaustion at their first
      ventilatory threshold in the heat (34.0 +/- 0.1  degrees  C, 52 +/- 3% relative
      humidity) following one of three 30 min pre-exercise manoeuvres: (1) ice slurry
      ingestion; (2) cold water immersion; or (3) warm fluid ingestion (control).
      Running time was longer following cold water immersion (56.8 +/- 5.6 min; P =
      0.008) and ice slurry ingestion (52.7 +/- 8.4 min; P = 0.005) compared with
      control (46.7 +/- 7.2 min), but not significantly different between cold water
      immersion and ice slurry ingestion (P = 0.335). During exercise, rectal
      temperature was lower with cold water immersion from 15 and 20 min into exercise
      compared with control and ice slurry ingestion, respectively, and remained lower
      until 40 min (P = 0.001). At exhaustion rectal temperature was significantly
      higher following ice slurry ingestion (39.76 +/- 0.36  degrees  C) compared with
      control (39.48 +/- 0.36  degrees  C; P = 0.042) and tended to be higher than cold
      water immersion (39.48 +/- 0.34  degrees  C; P = 0.065). As run times were
      similar between conditions, ice slurry ingestion may be a comparable form of pre
      cooling to cold water immersion.

PMID- 22132793
TI  - Rice hull smoke extract inactivates Salmonella Typhimurium in laboratory media
      and protects infected mice against mortality.
AB  - A previously characterized rice hull smoke extract (RHSE) was tested for
      bactericidal activity against Salmonella Typhimurium using the disc-diffusion
      method. The minimum inhibitory concentration (MIC) value of RHSE was 0.822%
      (v/v). The in vivo antibacterial activity of RHSE (1.0%, v/v) was also examined
      in a Salmonella-infected Balb/c mouse model. Mice infected with a sublethal dose
      of the pathogens were administered intraperitoneally a 1.0% solution of RHSE at
      four 12-h intervals during the 48-h experimental period. The results showed that
      RHSE inhibited bacterial growth by 59.4%, 51.4%, 39.6%, and 28.3% compared to
      78.7%, 64.6%, 59.2%, and 43.2% inhibition with the medicinal antibiotic
      vancomycin (20 mg/mL). By contrast, 4 consecutive administrations at 12-h
      intervals elicited the most effective antibacterial effect of 75.0% and 85.5%
      growth reduction of the bacteria by RHSE and vancomycin, respectively. The
      combination of RHSE and vancomycin acted synergistically against the pathogen.
      The inclusion of RHSE (1.0% v/w) as part of a standard mouse diet fed for 2 wk
      decreased mortality of 10 mice infected with lethal doses of the Salmonella.
      Photomicrographs of histological changes in liver tissues show that RHSE also
      protected the liver against Salmonella-induced pathological necrosis lesions.
      These beneficial results suggest that the RHSE has the potential to complement
      wood-derived smokes as antimicrobial flavor formulations for application to human
      foods and animal feeds. PRACTICAL APPLICATION: The new antimicrobial and anti
      inflammatory rice hull derived liquid smoke has the potential to complement
      widely used wood-derived liquid smokes as an antimicrobial flavor and health
      promoting formulation for application to foods.

PMID- 22132794
TI  - 2-Carboxy-D-arabinitol 1-phosphate (CA1P) phosphatase: evidence for a wider role
      in plant Rubisco regulation.
AB  - The genes for CA1Pase (2-carboxy-D-arabinitol-1-bisphosphate phosphatase) from
      French bean, wheat, Arabidopsis and tobacco were identified and cloned. The
      deduced protein sequence included an N-terminal motif identical with the PGM
      (phosphoglycerate mutase) active site sequence [LIVM]-x-R-H-G-[EQ]-x-x-[WN]. The
      corresponding gene from wheat coded for an enzyme with the properties published
      for CA1Pase. The expressed protein lacked PGM activity but rapidly
      dephosphorylated 2,3-DPG (2,3-diphosphoglycerate) to 2-phosphoglycerate. DTT
      (dithiothreitol) activation and GSSG inactivation of this enzyme was pH
      sensitive, the greatest difference being apparent at pH 8. The presence of the
      expressed protein during in vitro measurement of Rubisco (ribulose-1,5
      bisphosphate carboxylase/oxygenase) activity prevented a progressive decline in
      Rubisco turnover. This was due to the removal of an inhibitory bisphosphate that
      was present in the RuBP (ribulose-1,5-bisphosphate) preparation, and was found to
      be PDBP (D-glycero-2,3-pentodiulose-1,5-bisphosphate). The substrate specificity
      of the expressed protein indicates a role for CA1Pase in the removal of 'misfire'
      products of Rubisco.

PMID- 22132795
TI  - Functional genomics of trypanosomatids.
AB  - The decoding of the Tritryp reference genomes nearly 7 years ago provided a first
      peek into the biology of pathogenic trypanosomatids and a blueprint that has
      paved the way for genome-wide studies. Although 60-70% of the predicted protein
      coding genes in Trypanosoma brucei, Trypanosoma cruzi and Leishmania major remain
      unannotated, the functional genomics landscape is rapidly changing. Facilitated
      by the advent of next-generation sequencing technologies, improved structural and
      functional annotation and genes and their products are emerging. Information is
      also growing for the interactions between cellular components as transcriptomes,
      regulatory networks and metabolomes are characterized, ushering in a new era of
      systems biology. Simultaneously, the launch of comparative sequencing of multiple
      strains of kinetoplastids will finally lead to the investigation of a vast, yet
      to be explored, evolutionary and pathogenomic space.

PMID- 22132796
TI  - Successful treatment of orbital hemangioma with propranolol in a 5-year-old girl.
AB  - We report a 5-year-old girl, who presented with proptosis due to an orbital
      capillary hemangioma. After 8 months of treatment with oral propranolol at a dose
      of 2 mg/kg/day, the mass reduced significantly in size and regrowth was not
      observed within 20 months of follow-up.

PMID- 22132797
TI  - Risk factors for HR- and HER2-defined breast cancer in Slovenian postmenopausal
      women.
AB  - OBJECTIVE: The study aimed to investigate the influence of some generally
      recognized risk factors for hormone receptor (HR)- and human epidermal growth
      factor receptor 2 (HER2)-defined breast cancer among Slovenian postmenopausal
      women. METHOD: Eligible women diagnosed with breast cancer were compared with 709
      controls of the same age and ethnicity. Immunohistochemistry and FISH analyses
      were used to classify cases into molecular subtypes: 454 HR(+), 106 HR(-), 81
      HER2(+) and 603 HER2(-). Adjusted odds ratios and 95% confidence intervals were
      estimated using multivariate logistic regression analysis. RESULTS: Overweight
      and obese women were at increased risk of HR(+), HER2(-) and of HR(+), HR(-),
      HER2(-) tumors, respectively. Women who started menstruating at the age of 11
      years or earlier were at decreased risk of ER(-)PR(-) tumors. Users of hormone
      replacement therapy (HRT) were negatively associated with HR(+) and HER2(-)
      tumors. The inverse effect was most pronounced with the use of estrogen-only HRT,
      and longer duration of HRT use did not result in a significant change in risk. In
      contrast, combined HRT decreased the risk of HER2(+) tumors. Having a first
      degree relative with breast and/or ovarian cancer increased the risk of HR(+) and
      HER2(-) tumors. CONCLUSION: We conclude that certain breast cancer risk factors
      may vary by molecular subtypes. According to our results, HRT use may have a
      greater influence on HR (+) and HER2(-) breast cancers and the risk of HER2
      defined breast cancer may differ with respect to the regimen of HRT.

PMID- 22132799
TI  - A case series of thermal scald injuries in dogs exposed to hot water from garden
      hoses (garden hose scalding syndrome).
AB  - In this report, we present a series of cases of thermal burns (scalds) in dogs
      resulting from exposure to hot water from a garden hose that had been lying in
      the sun. These dogs typically inhabited the southern and western regions of the
      USA, where the recorded high temperatures often exceed 32 degrees C (90 degrees
      F) during the warm summer months. Dogs with thermal scald injury in these cases
      presented with linear thermal burns along the dorsum, in addition to a variety of
      other macroscopic lesions that were dependent upon the degree of burn exposure
      and ranged from local erythema to ulcerated, necrotic and sloughing skin.
      Chronic, healed wounds were often alopecic, with markedly thickened skin and
      characteristically smooth and glassy scar tissue formation. Histologically, the
      lesions of thermal scald injury in these dogs were indistinguishable from any
      other second or third degree burn, and consisted of full-thickness dermal and
      epidermal necrosis with occasional fibrinoid necrosis of vessel walls, vasculitis
      and intravascular thrombosis. Here, we closely examine 10 cases of dogs with
      dorsal thermal burns collected from Texas, Arizona, California, Utah, Nevada,
      Indiana, Michigan and North Carolina and propose the term 'garden hose scalding
      syndrome (GHS)' to describe this unique type of scald injury.

PMID- 22132800
TI  - Effect of glycemic index and fructose content in lunch on substrate utilization
      during subsequent brisk walking.
AB  - The purpose of the present study was to investigate the effect of glycemic index
      (GI) and fructose content in lunch on substrate utilization during subsequent
      brisk walking. Ten healthy young males completed 3 main trials in a
      counterbalanced crossover design. They completed 60 min of brisk walking at
      approximately 50% maximal oxygen consumption after consuming a standard breakfast
      and 1 of 3 lunch meals, i.e., a low GI meal without fructose (LGI), a low GI meal
      that included fructose beverage (LGIF), or a high GI meal (HGI). The 3 lunch
      meals were isocaloric and provided 1.0 g.kg-1 carbohydrate. Substrate utilization
      was measured using indirect respiratory calorimetry method. Blood samples were
      collected at certain time points. During the 2-h postprandial period after lunch,
      the incremental area under the blood response curve values of glucose and insulin
      were higher (p < 0.05) in the HGI trial than those in the LGI and LGIF trials
      (HGI vs. LGI and LGIF: glucose, 223.5 +/- 24.4 vs. 92.5 +/- 10.4 and 128.0 +/-
      17.7 mmol.min.L-1; insulin, 3603 +/- 593 vs. 1425 +/- 289 and 1888 +/- 114
      mU.min.L-1). During brisk walking, decreased carbohydrate oxidation was observed
      (p < 0.05) in the LGI trial than in the LGIF and HGI trials (LGI vs. LGIF and
      HGI: 60.8 +/- 4.0 vs. 68.1 +/- 6.0 and 74.4 +/- 4.7 g). No difference was found
      in fat oxidation among the 3 trials (LGI vs. LGIF vs. HGI: 21.6 +/- 2.3 vs. 19.2
      +/- 2.3 vs. 16.4 +/- 2.2 g). It appeared that fructose content was an important
      influencing factor when considering the effect of different GI lunch meals on
      substrate utilization during subsequent moderate intensity exercise.

PMID- 22132803
TI  - Superlow thermal conductivity 3D carbon nanotube network for thermoelectric
      applications.
AB  - Electrical and thermal transportation properties of a novel structured 3D CNT
      network have been systematically investigated. The 3D CNT net work maintains
      extremely low thermal conductivity of only 0.035 W/(m K) in standard atmosphere
      at room temperature, which is among the lowest compared with other reported CNT
      macrostructures. Its electrical transportation could be adjusted through a
      convenient gas-fuming doping process. By potassium (K) doping, the original p
      type CNT network converted to n-type, whereas iodine (I(2)) doping enhanced its
      electrical conductivity. The self-sustainable homogeneous network structure of as
      fabricated 3D CNT network made it a promising candidate as the template for
      polymer composition. By in situ nanoscaled composition of 3D CNT network with
      polyaniline (PANI), the thermoelectric performance of PANI was significantly
      improved, while the self-sustainable and flexible structure of the 3D CNT network
      has been retained. It is hoped that as-fabricated 3D CNT network will contribute
      to the development of low-cost organic thermoelectric area.

PMID- 22132804
TI  - Broad inhibition of plasmodium falciparum cytoadherence by (+)-epigallocatechin
      gallate.
AB  - BACKGROUND: The surface antigen PfEMP-1 is a key virulence factor of the human
      malaria parasite implicated in the cytoadherence of Plasmodium falciparum
      infected erythrocytes to a range of receptors on host endothelium. Among these
      host receptors, binding to ICAM-1 is related to cerebral malaria. The majority of
      the mortality in children with cerebral malaria is seen within 24 h of hospital
      admission despite the use of effective anti-parasite drugs, therefore, the
      development of adjunctive therapies is urgently needed.The polyphenolic compound
      (+)-epigallocatechin gallate ((+)-EGCG) has been previously evaluated for anti
      adhesive properties using a small number of laboratory parasite isolates. Here,
      this property is further explored using a new panel of ICAM-1-binding patient
      isolates of P. falciparum to ascertain if (+)-EGCG might be effective as a broad
      spectrum inhibitor of ICAM-1-based cytoadherence. METHODS: Plasmodium falciparum
      lines, including A4 and ItG as positive controls and nine new ICAM-1 binding
      patient isolates, were allowed to bind with ICAM-1-Fc protein under static assay
      conditions in the presence and absence of 50 MUM (+)-EGCG. Adhesion levels of all
      the parasite strains were quantified by microscopy as the mean number of infected
      erythrocyte (IE) bound per mm(2) of surface area and statistical comparisons were
      made to demonstrate the effect of (+)-EGCG on the binding of various parasite
      variants to human ICAM-1. RESULTS: This study revealed that binding of patient
      isolates to ICAM-1 was reduced significantly with inhibition levels of 37% in
      patient isolate BC-12 up to a maximum of 80% in patient isolate 8146 at 50 MUM
      (+)-EGCG. CONCLUSION: Evaluation of the anti-adhesive property of (+)-EGCG
      against a new panel of ICAM-1-binding patient isolates of P. falciparum showed
      that this inhibitor, identified as potential mimic of the L43 loop of human ICAM
      1, was effective at blocking cytoadherence.

PMID- 22132805
TI  - Desert hedgehog is a mammal-specific gene expressed during testicular and ovarian
      development in a marsupial.
AB  - BACKGROUND: Desert hedgehog (DHH) belongs to the hedgehog gene family that act as
      secreted intercellular signal transducers. DHH is an essential morphogen for
      normal testicular development and function in both mice and humans but is not
      present in the avian lineage. Like other hedgehog proteins, DHH signals through
      the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein
      distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial
      mammal (the tammar wallaby) to determine whether DHH signalling is a conserved
      factor in gonadal development in all therian mammals. RESULTS: DHH, PTCH1 and
      PTCH2 were present in the marsupial genome and highly conserved with their
      eutherian orthologues. Phylogenetic analyses indicate that DHH has recently
      evolved and is a mammal-specific hedgehog orthologue. The marsupial PTCH2
      receptor had an additional exon (exon 21a) not annotated in eutherian PTCH2
      proteins. Interestingly we found evidence of this exon in humans and show that
      its translation would result in a truncated protein with functions similar to
      PTCH1. We also show that DHH expression was not restricted to the testes during
      gonadal development (as in mice), but was also expressed in the developing ovary.
      Expression of DHH, PTCH1 and PTCH2 in the adult tammar testis and ovary was
      consistent with findings in the adult mouse. CONCLUSIONS: These data suggest that
      there is a highly conserved role for DHH signalling in the differentiation and
      function of the mammalian testis and that DHH may be necessary for marsupial
      ovarian development. The receptors PTCH1 and PTCH2 are highly conserved mediators
      of hedgehog signalling in both the developing and adult marsupial gonads.
      Together these findings indicate DHH is an essential therian mammal-specific
      morphogen in gonadal development and gametogenesis.

PMID- 22132806
TI  - Lower birth weight indicates higher risk of autistic traits in discordant twin
      pairs.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder of
      complex etiology. Although strong evidence supports the causal role of genetic
      factors, environmental risk factors have also been implicated. This study used a
      co-twin-control design to investigate low birth weight as a risk factor for ASD.
      METHOD: We studied a population-based sample of 3715 same-sex twin pairs
      participating in the Child and Adolescent Twin Study of Sweden (CATSS). ASD was
      assessed using a structured parent interview for screening of ASD and related
      developmental disorders, based on DSM-IV criteria. Birth weight was obtained from
      medical birth records maintained by the Swedish Medical Birth Registry. RESULTS:
      Twins lower in birth weight in ASD-discordant twin pairs (n=34) were more than
      three times more likely to meet criteria for ASD than heavier twins [odds ratio
      (OR) 3.25]. Analyses of birth weight as a continuous risk factor showed a 13%
      reduction in risk of ASD for every 100 g increase in birth weight (n=78).
      Analysis of the effect of birth weight on ASD symptoms in the entire population
      (most of whom did not have ASD) showed a modest association. That is, for every
      100 g increase in birth weight, a 2% decrease in severity of ASD indexed by
      scores on the Autism - Tics, attention-deficit hyperactivity disorder (AD/HD),
      and other Comorbidities (A-TAC) inventory would be expected in the sample as a
      whole. CONCLUSIONS: The data were consistent with the hypothesis that low birth
      weight confers risk to ASD. Thus, although genetic effects are of major
      importance, a non-genetic influence associated with birth weight may contribute
      to the development of ASD.

PMID- 22132807
TI  - Inhibitors of intravesicular acidification protect against Shiga toxin in a pH
      independent manner.
AB  - Shiga toxin inhibits protein synthesis after being transported from the cell
      surface to endosomes and retrogradely through the Golgi apparatus to the
      endoplasmic reticulum (ER) and into the cytosol. In this study, we have abolished
      proton gradients across internal membranes in different ways and investigated the
      effect on the various transport steps of Shiga toxin. Although inhibitors of the
      proton pump such as bafilomycin A1 and concanamycin A as well as some ionophores
      and chloroquine all protect against Shiga toxin, they mediate protection by
      inhibiting different transport steps. For instance, chloroquine protects the
      cells, although the toxin is transported to the ER. Importantly, our data
      indicate that proton pump activity is required for efficient endosome-to-Golgi
      transport of Shiga toxin, although acidification as such does not seem to be
      required.

PMID- 22132808
TI  - A possible case of caprine-associated malignant catarrhal fever in a domestic
      water buffalo (Bubalus bubalis) in Switzerland.
AB  - BACKGROUND: Malignant catarrhal fever (MCF) is a fatal herpesvirus infection,
      affecting various wild and domestic ruminants all over the world. Water buffaloes
      were reported to be particularly susceptible for the ovine herpesvirus-2 (OvHV-2)
      causing the sheep-associated form of MCF (SA-MCF). This report describes the
      first case of possibly caprine-associated malignant catarrhal fever symptoms in a
      domestic water buffalo in Switzerland. CASE PRESENTATION: The buffalo cow
      presented with persistent fever, dyspnoea, nasal bleeding and haematuria. Despite
      symptomatic therapy, the buffalo died and was submitted to post mortem
      examination. Major findings were an abomasal ulceration, a mild haemorrhagic
      cystitis and multifocal haemorrhages on the epicardium and on serosal and mucosal
      surfaces. Eyes and oral cavity were not affected. Histopathology revealed a mild
      to moderate lymphohistiocytic vasculitis limited to the brain and the urinary
      bladder. Although these findings are typical for MCF, OvHV-2 DNA was not detected
      in peripheral blood lymphocytes or in paraffin-embedded brain, using an OvHV-2
      specific real time PCR. With the aid of a panherpesvirus PCR, a caprine
      herpesvirus-2 (CpHV-2) sequence could be amplified from both samples.
      CONCLUSIONS: To our knowledge, this is the first report of malignant catarrhal
      fever in the subfamily Bovinae, where the presence of CpHV-2 could be
      demonstrated. The etiological context has yet to be evaluated.

PMID- 22132809
TI  - Safety and efficacy of tibolone and menopausal transition: a randomized, double
      blind placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy, safety and tolerability of Tibolone use
      during the menopausal transition (MT). METHODS: Sixty-five healthy women aged 40
      55 years (48.5 +/- 3.5 years) were recruited for a randomized, double-blind
      controlled trial. Thirty participants were recruited to receive oral Tibolone 2.5
      mg/day - Tibolone Group (TG), and 35 participants were assigned to the Placebo
      Group (PG), which received one capsule of lactose/day. Both groups were treated
      for 12 consecutive weeks. The Blatt-Kupperman Menopausal Index (KMI) and the
      Greene Climacteric Scale (GCS) were used. The glycaemic and lipid profiles,
      biochemical measures of hepatic function and endometrial thickness were measured
      for safety. A daily registry of complaints related to the treatment was
      maintained, and anthropometric measures were obtained to assess tolerability.
      RESULTS: A total of 57 women completed the study. After 12 weeks of Tibolone use,
      the total score and percentage of the KMI and GCS were significantly decreased
      compared to baseline, which reflected the efficacy of the treatment of
      climacteric symptoms. The improvement in blood biochemistry, endometrial atrophy
      and maintenance of the anthropometrical measures reflected the safety of Tibolone
      use. The absence of serious side effects demonstrated good tolerability for
      Tibolone use. CONCLUSIONS: The results showed good efficacy, tolerability and
      safety of Tibolone use during the MT.

PMID- 22132810
TI  - Association of pinch strength with hand dysfunction, finger deformities and
      contact points in patients with rheumatoid arthritis.

PMID- 22132811
TI  - Rapid determination of perv copy number from porcine genomic DNA by real-time
      polymerase chain reaction.
AB  - Here, we report the quantification of porcine endogenous retrovirus (PERV) copy
      numbers using real time PCR. After generating standard curves using plasmid DNA,
      copy numbers were determined for PERV pol and for a housekeeping gene, porcine
      estrogen receptor2 (ER2) with the same amount of genomic DNA. Using this method,
      we examined 6 pig breeds in Korea including two breeds of miniature pig, one
      domestic pig from Jeju, and imported pig breeds, Duroc, Landrace, and Yorkshire.
      All breeds showed PERV copy numbers ranging from 9 to 50. This method will be
      useful for monitoring of PERVs in a porcine xenograft.

PMID- 22132812
TI  - Isolation and characterization of embryonic stem cell-like cells from in vitro
      produced goat (Capra hircus) embryos.
AB  - The aim of the present study was to isolate and characterize goat embryonic stem
      cell-like cells from in vitro produced goat embryos. Inner cell mass (ICM) cells
      were isolated either mechanically or by enzymatic digestion from 150 blastocysts
      and 35 hatched blastocysts whereas 100 morulae were used for blastomeres
      isolation mechanically. The ICM derived cells or blastomeres were cultured on a
      feeder layer. The primary colony formation was significantly higher (P < 0.01)
      for hatched blastocysts (77.14%) than early/expanded blastocysts (54%) or morula
      (14%). When ICMs were isolated mechanically the primary colony formation for
      hatched blastocysts (90%) as well as blastocysts (66%) were significantly more
      than when ICMs were isolated by enzymatic digestion (60% and 30%, respectively).
      The colonies were disaggregated either mechanically or by enzymatic digestion for
      further subculture. When mechanical method was followed, the colonies remained
      undifferentiated up to 15 passages and three ES cell-like cell lines were
      produced (gES-1, gES-2, and gES-3). However, enzymatic disaggregation resulted in
      differentiation. The undifferentiated cells showed stem cell like morphological
      features, normal karyotype, and expressed stem cell specific surface markers like
      alkaline phosphatase, TRA-1-61, TRA-1-81, and intracellular markers Oct4, Sox2,
      and Nanog. Following prolonged culture of the ES cell-like cells were
      differentiated into several types of cells including neuron like and epithelium
      like cells. In conclusion, goat embryonic stem cell-like cells can be isolated
      from in vitro produced goat embryos and can be maintained for long periods in
      culture.

PMID- 22132813
TI  - Variation of telomerase activity and morphology in porcine mesenchymal stem cells
      and fibroblasts during prolonged in vitro culture.
AB  - The purpose of this study was to examine the telomerase activity, population
      doubling time (PDT), morphological alterations, and the cell cycle status with
      activity of senescence-associated-beta-galactosidase in porcine mesenchymal stem
      cells (MSCs) and fibroblasts during an extended in vitro culture. MSCs and
      fibroblasts were isolated from bone marrow and ear skin of a miniature pig,
      respectively, and cultured up to 20 passages. The analysis was carried out in
      MSCs and fibroblasts at 1, 5, 10, 15, and 20 passages. Relative telomerase
      activity (RTA) levels were significantly (P < 0.05) higher in MSCs than in
      fibroblasts at all the passages. The PDT and cellular size slightly increased in
      MSCs at later passages. In contrast, fibroblasts had significantly (P < 0.05)
      increased PDT and cellular size, and the morphology revealed senescent-like
      abnormal type after passage 10. Further, the high incidence of beta-galactosidase
      stained cells was observed in fibroblasts compared to that of MSCs at passage 15,
      and cell cycle stage at G0 / G1 phase was significantly (P < 0.05) increased in
      the fibroblasts at 15 and 20 passages compared to that of MSCs. Based on these
      observations, we concluded that porcine MSCs possessed more tolerance against
      senescence and aging compared to fibroblasts following prolonged in vitro
      culture.

PMID- 22132814
TI  - Assembly and in vitro functional analysis of zinc finger nuclease specific to the
      3' untranslated region of chicken ovalbumin gene.
AB  - Synthetic zinc finger nucleases (ZFNs) are useful for the improvement of site
      directed integration of foreign gene into vertebrate chromosomes. To facilitate
      site-directed integration of foreign genes into the 3'-untranslated region of the
      chicken ovalbumin gene, we have constructed ZFN expression vectors using Zinc
      Finger Consortium Vector Kits and tested the functionality of these ZFN
      constructs. Coding sequences for 6 zinc fingers were assembled following the
      modular assembly method. The zinc finger assembly was fused to two FokI catalytic
      domains. Various configurations of linker regions between domains were tested for
      their influence on enzymatic activity, using plasmid substrate containing the
      target sequence. Results indicated that ZFN with an elongated linker between two
      nuclease domains had a high catalytic activity.

PMID- 22132815
TI  - Construction of porcine growth hormone eukaryotic expression vector and its
      transfection mediated by cationic liposome in mice.
AB  - The present study was designed to construct the eukaryotic expression vector for
      pGH mature peptide (mpGH) and to investigate its transfection mediated by
      cationic liposome (CLs) in COS-7 cells and mice. The cDNA of mpGH ORF was
      successfully cloned by reverse transcription-PCR (RT-PCR) using the adult pig
      pituitary gland RNA. The recombinant eukaryotic expression vector, VmpGH, was
      constructed by ligating the cDNA fragment to the vector VR1020. The successful
      construction was confirmed by restriction enzyme digestion, and the expression of
      mpGH was confirmed by RT-PCR, immunofluorescence analyses (IFA), and ELISA in COS
      7 cells. The VmpGH and VR1020 plasmids were entrapped with CLs, and four
      experimental groups of male Kunming mice were administrated with VmpGH / lipoplex
      or naked VmpGH plasmids at two dosages (0.5 and 1.0 mg/kg), while the mice
      injected with VR1020-lipoplex at the dosage of 0.5 mg/kg body weight (BW) were
      used as control. The BWs of the mice administrated with VmpGH-lipoplex at both
      dosages were significantly higher than not only those of the control (P < 0.01)
      but also those of mice injected with naked plasmids (P < 0.01), from 30 to 60
      days post-transfection. The transcription of VmpGH was detected by RT-PCR in six
      tissues, including the liver, kidney, spleen, heart, muscle, and blood, of the
      mice injected with VmpGH-lipoplex, but not in the same tissues of control mice.
      Furthermore, the mice injected with VmpGH-lipoplex showed higher plasma GH
      contents than the control mice (P < 0.05), although their IgG contents did not
      show much difference. Our study demonstrates that the VmpGH plasmids'
      transfection mediated by CLs can significantly promote the growth of mice, which
      may be used to improve the livestock production.

PMID- 22132817
TI  - Ratio of lesional/non-lesional melanin index: a sensitive parameter for the
      evaluation of skin lightening agents.

PMID- 22132818
TI  - Characterization of economic requirements for a "carbon-debt-free country".
AB  - In recent years, greenhouse gas emission controls that incorporate the supply
      chains of products and services, thereby emphasizing the role of consumers rather
      than producers, have been drawing increasing attention. A country's consumption
      based emissions, including those due to global supply chains, reflect the total
      emissions on which the national economy relies. To design effective emissions
      control strategies there is therefore an urgent need for countries to elucidate
      the structural relationship between their domestic economy and emissions
      occurring through global supply chains. Here we consider the structural
      characteristics of consumption-based emissions in Japan, which in 2005 totaled
      1675 Mt CO(2)eq. Outside the country the Japanese economy generated global
      emissions of 541 Mt CO(2)eq, 35.7% of which were UNFCCC Annex I emissions and
      64.3% were non-Annex I and other emissions. This figure of 64.3% reveals that
      Japan is actually relying to a considerable degree on emissions that are subject
      to no international obligations. We identify key economic contributors to
      consumption-based emissions at the commodity level and specify items of household
      expenditure that are effective options for both financial savings and emissions
      reduction. We then discuss the importance of emissions control for evolving
      toward a "carbon-debt-free country".

PMID- 22132819
TI  - Influence of nutritional knowledge on the use and interpretation of Spanish
      nutritional food labels.
AB  - The present study analyzed the nutritional knowledge of Spanish consumers and its
      relationship with the correct use of food labels. Consumers were asked about
      their nutritional knowledge and some functional foods and about their
      understanding of food labeling and their use of it to select healthy food. A 2
      part questionnaire was employed. The 1st part concerned their knowledge of
      nutritional facts, including their knowledge about macronutrients and perception
      of certain functional foods, while the 2nd part addressed some questions
      regarding food labels. The results revealed no statistically significant
      differences in nutritional knowledge by either age or gender, but a direct
      relationship with educational level. The association between nutritional
      knowledge and the perception and understanding of food labeling showed that the
      nutritional label rarely influenced the food purchases of the group with low
      nutritional knowledge, who considered that this information was too technical.
      More than half of the consumers did not consider the calorie or sugar content
      important for selecting food. In addition, the group with low nutritional
      knowledge stated that they never or rarely looked at the food labels to check
      whether it was low-fat food that they were buying. PRACTICAL APPLICATION: Knowing
      the status of the consumer's nutritional knowledge allows health campaigns to be
      designed; considering the influence of cultural factors and the perception of
      food labeling is very useful for promoting better nutritional information.

PMID- 22132820
TI  - Up-regulated miR-17 promotes cell proliferation, tumour growth and cell cycle
      progression by targeting the RND3 tumour suppressor gene in colorectal carcinoma.
AB  - Emerging evidence indicates that the miR-17 family may have a causal role in
      human cancer tumorigenesis, but their specific effects on the occurrence of CRC
      (colorectal carcinoma) are still poorly understood. In the present study, we
      profiled CRC tissue samples by miRNA (microRNA) microarray and found that four
      members of the miR-17 family had higher expression in CRC tissues than in normal
      tissues. This finding was further validated by qRT-PCR (quantitative reverse
      transcription PCR). Transfecting CRC cells with an inhibitor of miR-17 lowered
      their ability to proliferate and induced G0/G1 arrest. We also confirmed that miR
      17 exerted this function by directly targeting RND3 in vitro, and that the
      expression of miR-17 was negatively correlated with that of RND3 in CRC tissues
      and CRC cells. Moreover, miR-17 inhibition led to tumour growth suppression and
      up-regulation of RND3 expression in a nude mouse xenograft model. RND3 expression
      was found to be significantly lower in CRC tissues than in normal tissues and
      adenomas, indicating that RND3 may act as a tumour suppressor gene in CRC. In
      conclusion, the present study suggests that miR-17 plays an important role in CRC
      carcinogenesis by targeting RND3 and may be a therapeutic agent for CRC.

PMID- 22132821
TI  - Axial ligand effect on the rate constant of aromatic hydroxylation by iron(IV)
      oxo complexes mimicking cytochrome P450 enzymes.
AB  - The cytochromes P450 are important iron-heme based monoxygenases that catalyze a
      range of different oxygen atom transfer reactions in nature. One of the key
      bioprocesses catalyzed by these enzymes is the aromatic hydroxylation of
      unactivated arenes. To gain insight into axial ligand effects and, in particular,
      how it affects aromatic hydroxylation processes by P450 model complexes, we
      studied the effects of the axial ligand on spectroscopic parameters (trans
      influence) as well as on aromatic hydroxylation kinetics (trans-effect) using a
      range of [Fe(IV)(O)(Por(+*))X] oxidants with X = SH(-), Cl(-), F(-), OH(-),
      acetonitrile, GlyGlyCys(-), CH(3)COO(-), and CF(3)COO(-). These systems give red
      shifted Fe-O vibrations that are dependent on the strength of the axial ligand.
      Despite structural changes, however, the electron affinities of these oxidants
      are very close in energy, but sharp differences in pK(a) values are found. The
      aromatic hydroxylation of the para-position of ethylbenzene was tested with these
      oxidants, and they all show two-state-reactivity patterns although the initial
      low-spin C-O bond formation barrier is rate determining. We show, for the first
      time, that the rate determining barrier for aromatic hydroxylation is
      proportional to the strength of the O-H bond in the corresponding iron(IV)
      hydroxo complex, i.e., BDE(OH), hence this thermochemical property of the oxidant
      drives the reaction and represents the axial ligand effect. We have rationalized
      our observed barrier heights for these axially ligated systems using
      thermochemical cycles and a valence bond curve crossing diagram to explain the
      origins of the rate constants.

PMID- 22132822
TI  - Direct tarsus to frontalis muscle sling without flap creation for correction of
      blepharoptosis with poor levator function.
AB  - PURPOSE: To report the outcomes of ptosis surgery in patients with weak levator
      function utilizing the direct tarsus to frontalis muscle sling technique without
      creation of a flap. METHODS: In a prospective nonrandomized case series over a 3
      year period, patients with ptosis and weak (less than 4 mm) levator function
      underwent direct sling of the tarsus to frontalis muscle without creating any
      flap. Success was defined as upper lid margin to central corneal reflex distance
      of at least 3 mm in bilateral cases and a difference of less than 1 mm in
      unilateral cases. RESULTS: Overall, 26 eyes of 22 patients with mean age of 15.4
      +/- 9.4 years were operated and followed up for 13.5 +/- 8.4 months. The ptosis
      was congenital in 15 patients (68.2%) and acquired in 7 patients (31.8%). Twelve
      patients (54.5%) had a history of ptosis surgery. The procedure was judged as
      successful in 77.3% of patients after initial surgery and in 100% after
      reoperation. Surgical success after initial surgery was directly correlated with
      the amount of levator function (P = 0.02). However, success was not associated
      with age (P = 0.9) or history of surgery (P = 0.9). None of the patients
      developed eyelid hematoma, lagophthalmus or dry eye. CONCLUSIONS: Direct sling of
      the upper tarsus to the frontalis muscle without creation of flap is an effective
      procedure for correction of ptosis in patients with weak levator function.
      Minimal dissection and preservation of the orbicularis oculi prevents
      lagophthalmus and its consequences.

PMID- 22132823
TI  - Varsity athletes have lower 2D:4D ratios than other university students.
AB  - The second to fourth digit ratio (2D:4D) is a sexually dimorphic trait with lower
      finger ratios considered more masculine. These digit ratios are believed to
      reflect the prenatal hormonal environment with higher exposure to androgens in
      utero leading to more masculine digit ratios. The 2D:4D ratio has been negatively
      correlated with many factors, including aggression, physical fitness, and
      athleticism. We compared 2D:4D finger ratios of (1) male and female varsity
      athletes (n = 99) versus male and female student non-athletes (n = 122), and (2)
      males (n = 104) versus females (n = 117). Our results confirmed that both male
      (mean +/- s(x) : 0.97 +/- 0.004) and female (0.98 +/- 0.005) varsity athletes had
      significantly lower ratios than their non-varsity peers (males: 0.99 +/- 0.004;
      females: 1.00 +/- 0.006), and that male athletes had significantly lower 2D:4D
      ratios than female athletes. Overall, males had significantly lower 2D:4D ratios
      than females (0.98 +/- 0.003 vs. 0.99 +/- 0.004). A smaller 2D:4D ratio appears
      to be consistent with participation in varsity sports among both males and
      females.

PMID- 22132824
TI  - Tuning exchange bias in core/shell FeO/Fe3O4 nanoparticles.
AB  - Monodisperse 35 nm FeO nanoparticles (NPs) were synthesized and oxidized in a dry
      air atmosphere into core/shell FeO/Fe(3)O(4) NPs with both FeO core and Fe(3)O(4)
      shell dimensions controlled by reaction temperature and time. Temperature
      dependent magnetic properties were studied on FeO/Fe(3)O(4) NPs obtained from the
      FeO NPs oxidized at 60 and 100  degrees C for 30 min. A large exchange bias
      (shift in the hysteresis loop) was observed in these core/shell NPs. The relative
      dimensions of the core and shell determine not only the coercivity and exchange
      field but also the dominant reversal mechanism of the ferrimagnetic Fe(3)O(4)
      component. This is the first time demonstration of tuning exchange bias and of
      controlling asymmetric magnetization reversal in FeO/Fe(3)O(4) NPs with
      antiferromagnetic core and ferrimagnetic shell.

PMID- 22132825
TI  - Ecological aspects of plant selenium hyperaccumulation.
AB  - Hyperaccumulators are plants that accumulate toxic elements to extraordinary
      levels. Selenium (Se) hyperaccumulators can contain 0.1-1.5% of their dry weight
      as Se, levels toxic to most other organisms. In this review we summarise what is
      known about the ecological functions and implications of Se (hyper)accumulation
      by plants. Selenium promotes hyperaccumulator growth and also offers a plant
      several ecological advantages through negative effects on Se-sensitive partners.
      High tissue Se levels reduce herbivory and pathogen infection, and high-Se litter
      deposition can inhibit neighbouring plants. There is no evidence for a cost of
      hyperaccumulation in terms of reproductive functions or pollinator visitation.
      Hyperaccumulators offer a niche for Se-tolerant herbivores, pollinators, microbes
      and neighbouring plants. They may even facilitate these partners through Se
      enrichment: neighbouring plants with elevated Se levels enjoy enhanced growth and
      reduced herbivory. Through combined negative and positive effects on ecological
      partners, Se hyperaccumulators likely affect local plant, microbial and animal
      species composition and richness, favouring Se-tolerant species at different
      trophic levels. By locally concentrating Se and altering its chemical form, Se
      hyperaccumulators likely play an important role in Se entry into, and Se cycling
      through, seleniferous ecosystems. These findings are of significance since they
      provide insight into the ecological reverberations of Se hyperaccumulation, and
      shed light on the possible selection pressures that have led to the evolution of
      this fascinating phenomenon. Better ecological insight will also help in the
      management of seleniferous areas and the agricultural production of Se-rich crops
      for phytoremediation or biofortification.

PMID- 22132826
TI  - Meiotic abnormalities underlying pollen sterility in wild potato hybrids and
      spontaneous populations.
AB  - Wild potato species are widely distributed in the Americas, where they
      spontaneously grow in very diverse habitats. These species - with low chromosome
      differentiation - form polyploid series with 2n = 2x, 3x, 4x and 6x (x =12). They
      are isolated in nature by external and internal hybridisation barriers that can
      be incomplete, allowing hybridisation in areas of sympatry. Nevertheless, most
      accessions in germplasm banks, regardless of genetic background of the sampled
      spontaneous populations, have been assigned specific categories based on
      morphological characters. To further investigate the extent of hybridisation in
      the group and for comparative purposes, pollen viability was estimated in (i)
      artificial hybrids between a commercial cultivar (Calen INTA) of the common
      potato (tetraploid Solanum tuberosum ssp. tuberosum) and the tetraploid cytotype
      of the related wild species S. gourlayi, and (ii) samples of plants (accessions)
      and inflorescences of natural populations from Argentina, tentatively classified
      as 'presumed hybrids' (S. infundibuliforme-S. gourlayi) and 'species' (S.
      infundibuliforme, S. gourlayi and S. chacoense). Regardless of origin, 98 out of
      103 plants analysed had zero to 70% pollen viability (zero to 40% in eight of
      them). Pollen grains were of variable size and morphology and, in mostly male
      sterile plants, the only viable pollen grains were 2n and/or 4n. Furthermore,
      male sterile plants shared various abnormalities in meiosis I and II (unpaired
      chromosomes, unequal chromosome distribution, precocious/lagging chromosomes,
      parallel, tripolar, fused and multiple spindles, unequal size nuclei, dyads,
      triads and pentads in addition to normal tetrads, among others). These results
      provide novel evidence to support field observations of early potato botanists on
      the extent of spontaneous hybridisation in wild Argentinian potato populations,
      which is not reflected in the current taxonomy and has significant consequences
      for germplasm conservation and breeding.

PMID- 22132827
TI  - Response of feline eosinophilic plaques and lip ulcers to amoxicillin trihydrate
      clavulanate potassium therapy: a randomized, double-blind placebo-controlled
      prospective study.
AB  - In this study, we evaluated the treatment of feline eosinophilic plaques and lip
      ulcers with amoxicillin trihydrate-potassium clavulanate (Clavamox((r)); Pfizer
      Animal Health). Nineteen cats with clinical and cytological findings consistent
      with eosinophilic plaques and/or lip ulcers were enrolled. Lesions were
      photographed and their areas measured in square centimetres before and after 21
      days of therapy with either flavoured amoxicillin-clavulanate suspension or
      flavoured placebo suspension. Sixteen cats completed the study, with nine plaque
      lesions (four treatment and five placebo) and eight lip ulcer lesions (four
      treatment and four placebo) included in the analysis. All lesions were shown to
      have infection, with bacterial phagocytosis present on cytological examination.
      Coagulase-positive staphylococci were the most commonly isolated bacteria. The
      amoxicillin-clavulanate-treated eosinophilic plaque group had a statistically
      significant 96.2% reduction in mean lesion size (-7.60 cm(2), P = 0.0078) and an
      80% reduction in mean percentage of microscopic fields demonstrating evidence of
      bacterial infection (P < 0.0001), whereas the placebo group did not. The
      amoxicillin-clavulanate-treated lip ulcer group had a 42.6% decrease in mean
      lesion size (-0.25 cm(2), P = 0.4125) and the placebo group a 36.6% increase
      (+0.49 cm(2), P = 0.1575), although neither change was statistically significant.
      The amoxicillin-clavulanate-treated lip ulcer group had a statistically
      significant 65.0% reduction in mean percentage of microscopic fields
      demonstrating evidence of bacterial infection (P < 0.0001), while no significant
      reduction was observed in the placebo group. A suspension of amoxicillin
      trihydrate-potassium clavulanate is an effective monotherapy for the treatment of
      feline eosinophilic plaques.

PMID- 22132828
TI  - Wealth inequality and utilization of reproductive health services in the Republic
      of Vanuatu: insights from the multiple indicator cluster survey, 2007.
AB  - BACKGROUND: Although the Republic of Vanuatu has improved maternal indicators,
      more needs to be done to improve equity among the poorest in the use of
      reproductive health services to expedite the progress towards the Millennium
      Development Goal 5(MDG 5) target. While large developing country studies provide
      evidence of a rich-poor gap in reproductive health services utilization, not much
      is written in terms of Pacific Islands. Thus, this study aims to examine the
      degree of inequality in utilization of reproductive health services in a
      nationally representative sample of Vanuatu households. METHODS: This paper used
      data from the 2007 Vanuatu Multiple Indicator Cluster Survey (MICS). The analyses
      were based on responses from 615 ever married women, living with at least one
      child below two years of age. Outcomes included antenatal care (ANC) and use of
      birth attendants at delivery, place of delivery, and counseling and testing for
      HIV/AIDS. Descriptive statistics and multivariate logistic regression methods
      were employed in the analysis. RESULTS: Findings revealed that the economic well
      being status of the household to which women belong, played a crucial role in
      explaining the variation in service utilization. Inequality in utilization was
      found to be more pronounced between the poorest and richest groups within the
      wealth quintiles. In adjusted models, mothers in the richest bands of wealth were
      5.50 (95% confidence interval [CI]: 1.34-22.47), 2.12 (95% CI: 1.02-3.42), 4.0
      (95% CI 1.58-10.10), and 2.0 (95% CI 1.02-5.88) times more likely to have
      assisted delivery from medically trained personnel, have institutional
      deliveries, and have counseling and testing for HIV/AIDS. CONCLUSIONS:
      Association between household wealth inequality and utilization of ANC and
      delivery assistance from medically trained personnel, institutional delivery, and
      counseling and testing for HIV/AIDS suggest that higher utilization of
      reproductive health care services in Vanuatu poor-rich inequalities need to be
      addressed. Reducing poverty and making services more available and accessible to
      the poor may be essential for improving overall reproductive health care
      utilization rate in Vanuatu.

PMID- 22132829
TI  - Effects of aromatase inhibitor on menopausal hyperplasia in a case of obesity.
AB  - The aromatase inhibitor anastrazole proved effective in the treatment of
      endometrial hyperplasia and postmenopausal bleeding in an obese 65-year-old woman
      with high operative risk. During anastrazole administration for 12 months, the
      endometrial thickness decreased from 9.8 mm to 2.4 mm and the control endometrial
      histology showed an atrophic endometrium. Uterine bleeding did not occur in the
      post-treatment, 3-year follow-up period. The endometrial thicknesses measured
      yearly by ultrasonography were 2.9, 3.5 and 3.3 mm. The plasma estradiol levels
      increased from < 73 pmol/l post-treatment to 112, 98 and 103 pmol/l. This case
      demonstrates that long-term aromatase inhibitor treatment can result in a
      refractory status of the endometrium and the estradiol produced in the adipose
      tissue does not exert a proliferative effect.

PMID- 22132830
TI  - Disaggregating the burden of substance dependence in the United States.

PMID- 22132831
TI  - Estrogen, alcohol consumption, and breast cancer.

PMID- 22132832
TI  - A new oral contraceptive regimen for endometriosis management: preliminary
      experience with 24/4-day drospirenone/ethinylestradiol 3 mg/20 mcg.
AB  - We report our preliminary experience with the use of a low-dose oral
      contraceptive containing Drospirenone/Ethinylestradiol 3 mg/20 mcg, both in
      cyclic and continuous regimen for endometriosis management. A total of 93 women
      were retrospectively included: 52 were treated by medical therapy (exclusive
      combined oral contraceptives (COC)-users), while 41 were submitted to surgery
      followed by postoperative therapy (postoperative COC-users). A clinical
      examination was performed at baseline and at 6-months follow-up. Presence and
      intensity of endometriosis-related symptoms were assessed by a visual analogue
      scale. Presence and dimension of endometriotic lesions were evaluated by
      transvaginal ultrasonography. Adverse effects and tolerability were analysed. In
      exclusive COC-users, significant reductions in dysmenorrhoea and dyspareunia
      scores and in endometrioma mean diameter were observed at follow-up. In
      postoperative COC-users, anatomical and symptom recurrence rates at follow-up
      were 4.9% and 17%, respectively. The most frequent adverse effects were spotting
      and headache. No difference between cyclic and continuous regimen in terms of
      symptom relief, lesion progression and tolerability was observed. From our
      preliminary experience, Drospirenone/Ethinylestradiol 3 mg/20 mcg seems to be
      promising in endometriosis management.

PMID- 22132833
TI  - Different hierarchical nanostructured carbons as counter electrodes for CdS
      quantum dot solar cells.
AB  - CdS quantum dot sensitized solar cells based on TiO(2) photoanode and
      nanostructured carbon as well as Pt as counter electrodes using iodide/triiodide
      and polysulfide electrolytes were fabricated to improve the efficiency and reduce
      the cost of solar cells. Compared with conventional Pt (eta = 1.05%) and CMK-3
      (eta = 0.67%) counter electrodes, hollow core-mesoporous shell carbon (HCMSC)
      counter electrode using polysulfide electrolyte exhibits much larger incident
      photon to current conversion efficiency (IPCE = 27%), photocurrent density (J(sc)
      = 4.31 mA.cm(-2)) and power conversion efficiency (eta = 1.08%), which is
      basically due to superb structural characters of HCMSC such as large specific
      surface area, high mesoporous volume, and 3D interconnected well-developed
      hierarchical porosity network, which facilitate fast mass transfer with less
      resistance and enable HCMSC to have highly enhanced catalytic activity toward the
      reduction of electrolyte shuttle.

PMID- 22132834
TI  - Evolution of reproductive mode variation and host associations in a sexual
      asexual complex of aphid parasitoids.
AB  - BACKGROUND: The Lysiphlebus fabarum group is a taxonomically poorly resolved
      complex of aphid parasitoids, presently split into three described species that
      comprise sexual (arrhenotokous) and asexual (thelytokous) lineages of unknown
      relationship. Specifically, it is unclear how asexuals evolved from sexuals in
      this system, to what extent reproductive modes are still connected by genetic
      exchange, how much the complex is structured by geography or by host-associated
      differentiation, and whether species designations are valid. Using a combination
      of population genetic and phylogenetic approaches, we addressed these issues in a
      comprehensive sample of parasitoid wasps from across Europe. RESULTS: Asexual
      reproduction predominated in parasitoids of the L. fabarum group, with asexual
      populations exhibiting high genotypic diversity. Sexual populations were only
      common in southern France; elsewhere sexual reproduction was restricted to
      specific aphid hosts. Although reproductive modes were aggregated on the
      mitochondrial genealogy and significantly differentiated at nuclear
      microsatellite loci, there was clear evidence for genetic exchange, especially on
      hosts attacked by sexual and asexual parasitoids. The microsatellite data further
      revealed that parasitoids collected from certain host aphids were significantly
      differentiated, yet the mitochondrial sequence variation across the entire L.
      fabarum group did not exceed 1.32% and exhibited a very shallow topology.
      Morphological characters used for delineation of described species were found to
      be phylogenetically non-conservative. CONCLUSIONS: Our results suggest that the
      sexual-asexual L. fabarum group represents a young complex of lineages with
      incomplete isolation between reproductive modes. We propose three mechanisms of
      genetic exchange that may jointly explain the high genotypic diversity observed
      in asexual parasitoids: (i) the formation of new asexual lineages via 'contagious
      parthenogenesis', (ii) introgression from sexual lineages through matings between
      sexual males and thelytokous females, and (iii) 'cryptic sex' within asexuals,
      mediated by rare males that thelytokous lines are known to produce spontaneously.
      The partially strong differentiation among wasps collected from different aphids
      suggests that host specialization can evolve readily in these parasitoids.
      Finally, we conclude that in the light of our data, the current taxonomic
      division of the L. fabarum group into three species cannot be upheld.

PMID- 22132835
TI  - Antioxidant alpha-tocopherol checks lymphoma promotion via regulation of
      expression of protein kinase C-alpha and c-Myc genes and glycolytic metabolism.
AB  - Overproduction of reactive oxygen species (ROS) due to environmental challenge or
      metabolic imbalance leads to oxidative stress, causing overactivation of a number
      of oncogenes that promote cancer development. Therefore, antioxidants should be
      able to check cancer growth by modulating oncogene activity. The requirement of
      high energy during unlimited cell proliferation is fulfilled by the switching of
      cancerous cells to a fast glycolytic pathway bypassing the oxygen dependent
      respiratory pathway. Almost all cancers exhibit a high expression of lactate
      dehydrogenase A (LDH-A) to ensure a high energy supply. The present study focused
      on modulating redox-sensitive oncogenes such as protein kinase C (PKC) and c-Myc
      by treatment of lymphoma bearing mice with the antioxidant alpha-tocopherol, the
      most active component of vitamin E. Further, the impact of alpha-tocopherol on
      LDH activity was tested. The results showed down-regulation of expression of
      stress-activated genes PKC-alpha, c-Myc and LDH-A by alpha-tocopherol in
      cancerous mice. alpha-Tocopherol contributes to the check of cell proliferation
      by decreasing the activity of LDH-A.

PMID- 22132836
TI  - Risk factors for development of pneumonitis after high-dose chemotherapy with
      cyclophosphamide, BCNU and etoposide followed by autologous stem cell transplant.
AB  - Pneumonitis is a complication of high-dose chemotherapy and autologous stem cell
      transplant (HDC-ASCT) regimens containing BCNU. Our goal was to define the
      incidence and risk factors for pneumonitis in patients with lymphoma receiving a
      uniform conditioning regimen in the modern era. We studied 222 patients who
      received HDC-ASCT using cyclophosphamide, BCNU and VP-16 (CBV). Pneumonitis
      incidence was 22%, with 19% receiving systemic corticosteroid treatment and 8%
      requiring inpatient hospitalization for pneumonitis. Three patients died
      secondary to pneumonitis-related complications. The following variables were
      independently associated with pneumonitis: prior mediastinal radiation (odds
      ratio [OR] 6.5, 95% confidence interval [CI] 2.3-18.9, p = 0.0005), total BCNU
      dose above 1000 mg (OR 3.4, 95% CI 1.3-8.7, p = 0.012) and age less than 54 (OR
      3.0, 95% CI 1.4-6.5, p = 0.0037). Increased vigilance for symptoms of pneumonitis
      is warranted for patients with prior mediastinal radiation and for younger
      patients, and dose reduction may be considered for patients who would receive
      greater than 1000 mg of BCNU.

PMID- 22132837
TI  - Donor leukocyte infusions in recurrent Hodgkin lymphoma following allogeneic stem
      cell transplant: 10-year experience at the M. D. Anderson Cancer Center.

PMID- 22132838
TI  - Association between methylenetetrahydrofolate reductase polymorphism C677T and
      risk of chronic myeloid leukemia in Serbian population.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the
      intracellular folate metabolism which plays an important role in carcinogenesis
      through DNA methylation and nucleotide synthesis. The common MTHFR single
      nucleotide polymorphism C677T has been reported to be associated with reduced
      enzymatic activity. In order to investigate the influence of this polymorphism on
      the risk of chronic myeloid leukemia (CML), we performed a case-control study in
      a Serbian population of 52 patients with CML and 53 healthy control subjects.
      MTHFR C677T polymorphism genotyping was assessed using the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results
      demonstrated no statistical difference in MTHFR 677 frequency distribution
      between patient and control groups. Our findings suggest that MTHFR 677 gene
      variants have no significant influence on the susceptibility to CML in a Serbian
      population.

PMID- 22132839
TI  - Successful intravenous immunoglobulin treatment for steroid-resistant
      eosinophilic enteritis in a patient with systemic lupus erythematosus.
AB  - Eosinophilic gastroenteritis is a rare condition of unknown etiology
      characterized by eosinophilic infiltration of the bowel. Corticosteroids are the
      mainstay of EG therapy. Although rare, steroid-resistant EG could be a life
      threatening condition with tissue destructive evolution. Associations of
      eosinophilic gastroenteritis with systemic lupus erythematosus have rarely been
      reported. In this report we describe a case of successful IVIG treatment in a
      patient with systemic lupus erythematosus and steroid-refractory eosinophilic
      gastroenteritis.

PMID- 22132840
TI  - Comparison of alternative models for personality disorders, II: 6-, 8- and 10
      year follow-up.
AB  - BACKGROUND: Several conceptual models have been considered for the assessment of
      personality pathology in DSM-5. This study sought to extend our previous findings
      to compare the long-term predictive validity of three such models: the five
      factor model (FFM), the schedule for nonadaptive and adaptive personality (SNAP),
      and DSM-IV personality disorders (PDs). METHOD: An inception cohort from the
      Collaborative Longitudinal Personality Disorder Study (CLPS) was followed for 10
      years. Baseline data were used to predict long-term outcomes, including
      functioning, Axis I psychopathology, and medication use. RESULTS: Each model was
      significantly valid, predicting a host of important clinical outcomes. Lower
      order elements of the FFM system were not more valid than higher-order factors,
      and DSM-IV diagnostic categories were less valid than dimensional symptom counts.
      Approaches that integrate normative traits and personality pathology proved to be
      most predictive, as the SNAP, a system that integrates normal and pathological
      traits, generally showed the largest validity coefficients overall, and the DSM
      IV PD syndromes and FFM traits tended to provide substantial incremental
      information relative to one another. CONCLUSIONS: DSM-5 PD assessment should
      involve an integration of personality traits with characteristic features of PDs.

PMID- 22132842
TI  - Transposed cheek flap in lower lid reconstruction: a retrospective case note
      review.
AB  - PURPOSE: To review the results of a cohort of patients that had a transposed
      cheek flap as part of the lower lid reconstruction. METHODS: Patients were
      identified from a database and a retrospective case note review was conducted. 21
      patients were identified but one set of notes was not traceable. 21 lids of 20
      patients were included. Data included age, sex, laterality, date and details of
      surgery and follow up as well as details of any complications and additional
      surgery where required. Data was collected and analysed using Microsoft Excel.
      RESULTS: 9 male and 11 female patients were included. Median age was 51. Follow
      up ranged from 5 to 176 months (median 34). The posterior lamella was
      reconstructed in 13 patients. Complications included bulky lids and ectropion as
      well as a few cases of corneal irritation from dermal hairs. 8 cases had no
      complications. 7 cases required revision--2 for trichiasis, 2 for bulky lids and
      3 for ectropion. CONCLUSION: The transposed cheek flap is a useful technique in
      the reconstruction of lower lid lesions involving the lateral canthus. The
      majority of patients had a good cosmetic result and required no further
      intervention. The most frequent complications were bulky lids and ectropion.

PMID- 22132841
TI  - Optical encoding by plasmon-based patterning: hard and inorganic materials become
      photosensitive.
AB  - The photosensitivity of nanocomposite AlN films with embedded silver nanospheres
      is reported. It stems from localized surface plasmon resonances (LSPR) whose
      modulation is photoinduced by laser annealing that induces a combined effect of
      metallic nanoparticle enlargement and dielectric matrix recrystallization; the
      photoindunced changes of the refractive index of the matrix result in strong
      spectral shift of LSPR. We demonstrate the utilization of this process for
      spectrally selective optical encoding into hard, durable, and chemically inert
      films.

PMID- 22132843
TI  - Outcome of deep lateral wall rim-sparing orbital decompression in thyroid
      associated orbitopathy: a new technique and results of a case series.
AB  - PURPOSE: To describe a new technique for deep lateral (single) wall orbital
      decompression surgery, developed by Mr. Geoffrey Rose, for proptosis in patients
      with thyroid-associated orbitopathy and to analyse the results achieved in our
      series. METHODS: The study is an interventional, retrospective, non-comparative
      case series. Twenty-one eyes of seventeen patients underwent the described
      technique of deep lateral wall orbital decompression for thyroid-associated
      orbitopathy. All patients had controlled thyroid functions and underwent surgery
      for cosmetic rehabilitation, with analysis of the reduction in proptosis, changes
      in visual acuity and post-operative complications. The surgery involved removing
      the lateral orbital wall whilst preserving the lateral rim, the lateral wall
      being approached through a horizontal skin incision placed lateral to the lateral
      canthus. After reflecting the periosteum, most of the bone (deep lateral wall)
      between the skull base and inferior orbital fissure is removed. RESULTS: A mean
      reduction in proptosis of 4.81 mm +/- 1.23 (SD) (p < 0.0001) with a median of 5.0
      mm (range 3-7 mm) was achieved and the best-corrected visual acuity was
      maintained in all patients. There were no complications during surgery, and post
      operative complications included worsening of pre-existing diplopia in one
      patient (6%) and transient cheek/temple numbness seen in three patients (18%).
      CONCLUSIONS: This technique of deep lateral wall orbital decompression developed
      by Mr. Rose is a safe and effective procedure for patients with mild to moderate
      proptosis. It carries a low risk of morbidity and avoids complications associated
      with decompressing the floor and medial wall, including new onset of motility
      disorders.

PMID- 22132844
TI  - Low dose orbital radiotherapy for thyroid eye disease.
AB  - PURPOSE: The use of low dose orbital radiotherapy for thyroid eye disease (TED)
      remains controversial. This is a review of patients with TED treated with
      radiotherapy in our department over the last twelve years. METHODS AND MATERIALS:
      Fifty-nine consecutive patients received low dose orbital radiotherapy of 20 Gray
      (Gy) for active TED at the Beatson Oncology Centre. Their records were
      retrospectively reviewed and data including duration of symptoms, clinical
      activity score (CAS) pre- and post-orbital radiotherapy, immunosuppression
      requirement, subjective assessment and range of rehabilitative surgery was
      collected. RESULTS: Before orbital radiotherapy, all fifty-nine patients had an
      initial response to glucocorticoids and therefore presumed to have active phase
      thyroid eye disease. They received retro-orbital radiotherapy of 20 Gy in 12
      fractions over 2 weeks. After treatment, only five patients remained on steroids
      and only one patient had CAS >= 3 at last follow up. Response (change in CAS) to
      orbital radiotherapy was statistically significant from 3.17 +/- 1.75 standard
      deviation (SD) to 0.73 +/- 0.92 SD (P < 0.001) at mean follow up of 6.5 months.
      There was a reduction in CAS at each subsequent follow up for all subgroups when
      the patients were grouped according to disease severity i.e. mild TED(CAS 1-2),
      moderate (CAS 3-4), severe CAS (5-7) and optic neuropathy. CONCLUSIONS: We
      believe orbital radiotherapy has a definite role to play in the treatment of
      active thyroid eye disease. The majority of our patients experienced a reduction
      in their clinical activity scores after orbital radiotherapy and this was
      irrespective of the severity of thyroid eye disease.

PMID- 22132845
TI  - Stability of eyelid height after graded anterior-approach lid lowering for
      dysthyroid upper lid retraction.
AB  - OBJECTIVE: To investigate the outcome of a modified anterior approach surgical
      procedure for the correction of primary upper eyelid retraction in thyroid eye
      disease. METHODS: A retrospective review of 52 consecutive cases (in 32 patients)
      of anterior-approach graded upper lid lowering for the treatment of primary
      eyelid retraction, carried out at Moorfields Eye Hospital between 2006-2009 was
      conducted. Measurements of upper margin-reflex distance (MRD), upper lid skin
      crease height and skin fold height were taken from clinical records and
      photographs. A comparison between pre-operative and both early and late post
      operative measurements was conducted, with a maximal follow-up of 12 months.
      Surgery was considered successful when all of the following criteria were met; an
      upper lid margin covering 0.5-1.5 mm of the superior cornea in the 12 o'clock
      position, smooth eyelid contour, skin crease height within 6-10 mm or upper lid
      skin fold within 2-5 mm of the lid margin, symmetry of lid position (difference
      in MRD of < 1 mm between both eyes) and patient satisfaction. RESULTS: A
      successful outcome was achieved in 86.5% (45/52) of lids with a single procedure.
      For the whole group, the mean MRD was 7.0 mm pre-operatively and 3.6 mm at 1
      month after surgery. The corresponding values from photographic estimates were
      6.5 mm and 3.6 mm, respectively. These values remained stable over the maximum
      follow-up period of 12 months. Under-correction occurred in 6/52 (11.5%) lids,
      one of which had persistent lateral flare, whereas over-correction occurred in
      1/52 (2%). CONCLUSIONS: The described surgical approach produces reasonably
      predictable and stable outcome for upper eyelid lowering in patients with thyroid
      eye disease.

PMID- 22132846
TI  - Large cell carcinoma of the lacrimal gland diagnosed by fine needle aspiration
      biopsy.
AB  - A 67-year-old man presented with a 6-month history of a malignant appearing left
      lacrimal gland mass. Fine needle aspiration biopsy was performed in the office,
      diagnosing the mass as large cell carcinoma (LCCA) of the lacrimal gland. This
      represents the second reported case of LCCA of the lacrimal gland and details the
      potential for FNA biopsy to successfully yield the diagnosis. LCCA of the
      lacrimal gland is rare, but should be considered in cases of malignant lacrimal
      gland neoplasms.

PMID- 22132847
TI  - Primary orbital extraskeletal osteosarcoma.
AB  - The authors describe a case of orbital extraskeletal osteosarcoma. A 78-year-old
      man with a history of rheumatoid arthritis on long-term corticosteroids had a
      left medial canthal basal cell carcinoma excision followed by adjuvant
      radiotherapy. Twelve months later, he re-presented with a large rapidly-growing
      calcified mass involving his left medial canthus and orbit. An incisional biopsy
      demonstrated an infiltrate of atypical cells exhibiting mitotic activity with a
      rosette arrangement around partially calcified necrotic tissue. The patient
      underwent orbital exenteration and a partial maxillectomy. Histopathology
      demonstrated an extraskeletal osteosarcoma. It is extremely rare for this tumor
      to occur in the orbit. Immunosuppression and adjuvant radiotherapy were possible
      predisposing factors in the development of this tumor. Extraskeletal osteosarcoma
      (ESOS) is a malignant tumour that produces osteoid. It develops in soft tissue
      without continuity to bone or periosteum. It is rare and comprises fewer than 5%
      of all osteosarcomas. Extraskeletal osteosarcoma primarily affects patients above
      50 years of age and has a poor prognosis. In this report, we describe the
      clinical, radiologic, and pathologic records of a rare case of primary ESOS of
      the orbit.

PMID- 22132848
TI  - Basal cell adenocarcinoma of lacrimal gland.
AB  - Basal cell adenocarcinoma (BCAC) is a recently described rare salivary gland
      tumor. They are locally invasive and destructive tumors with rare incidence of
      metastasis. BCAC most commonly occur in the parotid gland followed by the
      submandibular and other minor salivary glands. The primary management of these
      tumors is surgery with or without adjuvant radiotherapy. Lacrimal gland is a very
      rare location of BCAC; only one case has been reported in English literature. We
      report a case of recurrent basal cell adenocarcinoma of lacrimal gland in a 75
      year-old female. She had past history of local excision of a tumor in the
      lacrimal gland of same side 10 years back, details of which were not available
      with the patient. We discuss about the case and review the literature about
      treatment modality in basal cell adenocarcinoma.

PMID- 22132849
TI  - Postoperative eyelid infection in a patient taking etanercept.
AB  - Postoperative eyelid infections are a rare complication of eyelid surgery. The
      authors present a case of an eyelid infection occurring within the first week
      following surgery in a patient taking etanercept--a biologic anti-TNF-alpha agent
      used in the treatment of rheumatoid arthritis. The authors urge caution regarding
      the use of steroid/antibiotic combination ointments and systemic steroids in
      patients undergoing elective eyelid surgery who are on such medications.
      Perioperative discontinuation of etanercept in consultation with the prescribing
      physician may also be considered. Eyelid infections following eyelid surgeries
      such as blepharoplasty and ptosis correction are uncommon.( 1 , 2 ) A review of a
      large series of blepharoplasty procedures estimated the rate of postoperative
      infection at 0.2%.( 3 ) However, patients who are relatively immunosuppressed may
      be at a higher risk of developing skin and eyelid infections. We present a case
      of postoperative infection in a patient who was taking etanercept (Enbrel,
      Immunex Corporation, Thousand Oaks, CA) for rheumatoid arthritis.

PMID- 22132850
TI  - Autoenucleation resulting in carotid thrombosis, subdural hemorrhage, stroke, and
      death.
AB  - A 46-year-old man with schizoaffective disorder suffered carotid thrombosis,
      subdural hemorrhage, and stroke resulting in death following autoenucleation of
      the left globe. This is the first reported case of carotid thrombosis as a result
      of autoenucleation.

PMID- 22132851
TI  - Orbital inflammation: a rare association of common variable immunodeficiency.
AB  - PURPOSE: Ocular associations with common variable immunodeficiency (CVID) are
      very rare which include granulomatous uveitis, mulitfocal choroiditis and retinal
      vasculitis. However there have been no reports of orbital involvement, either
      inflammatory or neoplastic in association with CVID. We describe a unique case of
      a patient with CVID who developed orbital inflammation. METHODS: Clinical,
      histological and radiological findings and the management of this case is
      presented. RESULTS: A 58 year old male with known CVID treated with regular
      intravenous immunoglobulin infusion, presented with left peri-orbital redness,
      pain, proptosis and restriction of ocular movements. CT scan showed an ill
      defined mass in the left lateral orbit, adjacent to the lacrimal gland. An
      orbital biopsy revealed a monomorphic lymphocytic infiltrate forming loose
      lymphoid aggregates in the lacrimal gland tissue. Immunocytochemistry confirmed
      this to be a reactive inflammatory infiltrate. The patient was successfully
      treated with a course of oral prednisolone which resulted in improvement of
      orbital inflammation, ocular movements and proptosis. CONCLUSION: To our
      knowledge this is the first reported case of non-granulomatous orbital
      inflammation in association with CVID. This case serves to remind
      ophthalmologists encountering a patient with CVID that they may have associated
      orbital inflammatory disease which is responsive to steroid therapy similar to
      sterile inflammatory masses described in other organs.

PMID- 22132852
TI  - Apocrine hidrocystoma of the orbit.
AB  - Apocrine hidrocystomas are benign cysts of sweat duct origin, originating mainly
      from the apocrine secretory glands of Moll. They are typically encountered in the
      head and neck, particularly around the inner canthus of the eyelid. An
      intraorbital location of this lesion is extremely rare but should be considered
      in the differential diagnosis of a painless cystic lesion in the ocular adnexa at
      any age.

PMID- 22132857
TI  - Correction of vibrational broadening in molecular dynamics clusters with the
      normal mode optimization method.
AB  - Vibrational properties of solutions are frequently simulated with clusters of a
      solute and a few solvent molecules obtained during molecular dynamics (MD)
      simulations. The raw cluster geometries, however, often provide unrealistic
      vibrational band broadening, for both ab initio and empirical force fields. In
      this work, partial optimization in normal-mode coordinates is used on empirical
      basis to reduce the broadening. The origin of the error is discussed on a
      simplified two-dimensional system, which indicates that the problem is caused by
      the anharmonic MD potential, mode coupling, and neglect of quantum effects. Then
      the procedure of partial geometry optimization on Raman and Raman optical
      activity (ROA) spectra is applied and analyzed for the solvated lactamide
      molecule. Comparison to experiment demonstrates that the normal-mode partial
      optimization technique with a suitable frequency limit can significantly reduce
      the broadening error. For lactamide, experimental and simulated vibrational
      bandwidths are compared; the most realistic theoretical spectra are obtained for
      partially optimized clusters with the vibrational wavenumber cutoff of about 200
      cm(-1).

PMID- 22132854
TI  - Harnessing the genetic toolbox for the benefit of the racing Thoroughbred.
AB  - The understanding and application of genetics have grown extremely quickly since
      it has become possible to sequence the whole genome of an organism. The human
      genome sequence was completed in 2001 and that of the horse in 2007. The
      significance of this is that it makes it more feasible to explain how both
      genetically simple and complex traits are transmitted from one generation to the
      next and, therefore, to make informed breeding decisions, modify how horses are
      managed and trained to minimise the risk of disease and injury, and improve
      methods of prevention, diagnosis and treatment of many conditions. The science of
      genetics/genomics will continue to grow internationally, limited only by the
      funds available. The application of the science to man, horses and other species
      raises very complex moral and commercial issues. Thoroughbred breeders are
      perceived by some as resistant to change, but their apparent intransigence is
      often based on a genuine concern for the integrity of the breed. By taking
      control of the application of the advances in genetics, the Thoroughbred industry
      potentially has the opportunity to improve both the health and performance of
      Thoroughbreds. If, however, the science is applied in an uncoordinated manner,
      driven by commercial interests with no underlying concern for the horses
      themselves, there is a very real risk that breeders, the Thoroughbred breed and
      individual horses will all suffer as a consequence.

PMID- 22132858
TI  - The crystal structure of human UDP-glucose pyrophosphorylase reveals a latch
      effect that influences enzymatic activity.
AB  - UGPase (UDP-glucose pyrophosphorylase) is highly conserved among eukaryotes.
      UGPase reversibly catalyses the formation of UDP-glucose and is critical in
      carbohydrate metabolism. Previous studies have mainly focused on the UGPases from
      plants, fungi and parasites, and indicate that the regulatory mechanisms
      responsible for the enzyme activity vary among different organisms. In the
      present study, the crystal structure of hUGPase (human UGPase) was determined and
      shown to form octamers through end-to-end and side-by-side interactions. The
      observed latch loop in hUGPase differs distinctly from yUGPase (yeast UGPase),
      which could explain why hUGPase and yUGPase possess different enzymatic
      activities. Mutagenesis studies showed that both dissociation of octamers and
      mutations of the latch loop can significantly affect the UGPase activity.
      Moreover, this latch effect is also evolutionarily meaningful in UGPase from
      different species.

PMID- 22132860
TI  - N-acyl-homoserine lactones from Enterobacter sakazakii (Cronobacter spp.) and
      their degradation by Bacillus cereus enzymes.
AB  - A chemical study of acyl-homoserine lactones (acyl-HSLs) produced by Enterobacter
      sakazakii resulted in the identification of three molecules: (S)-N-heptanoyl-HSL,
      (S)-N-dodecanoyl-HSL and (S)-N-tetradecanoyl-HSL. Mixed cultures of E. sakazakii
      and Bacillus cereus depleted E. sakazakii acyl-HSLs, suggesting acyl-HSL
      degradation by B. cereus hydrolases (hydrolysis of the lactone or amide moiety).
      The expression of B. cereus acyl-HSL lactonase and acyl-homoserine acylase was
      confirmed by monitoring the biotransformation of (S)-N-dodecanoyl-HSL into (S)-N
      dodecanoyl-homoserine, dodecanoic acid and homoserine in the presence of B.
      cereus whole cells, using electrospray-mass spectrometry (ESI-MS).

PMID- 22132859
TI  - Analysis of protein fractions and some minerals present in chan (Hyptis
      suaveolens L.) seeds.
AB  - Chan (Hyptis suaveolens L.) seeds have been used as food as well as in
      traditional medicine in several countries of America, Asia and Africa. Chan seed
      protein content was 13.9% on dry weight basis. Analysis of its protein
      composition showed 39% globulins, 36% glutelins, 24% albumins, and 1% prolamins.
      By defatting the flour with chloroform/methanol, it increased the extracted
      proteins and improved the protein band resolution after SDS-PAGE, showing 5
      albumin bands, 8 globulin bands, and 2 prolamin and glutelin bands. The aromatic
      amino acid content in chan seeds is higher than those of other grains including
      maize, with good levels of branched chain amino acids. In general, except for
      lysine, it has a well-balanced amino acid composition, providing a good supply of
      almost all the essential amino acids for the different age groups. Magnesium
      content was high, whereas calcium, potassium, and phosphorous were in the average
      range when compared to barley, oat, rice, and wheat. The present results indicate
      that seeds from the chan plant could be relevant because of their nutritional
      properties and they have the potential to be widely used in the production of
      high-quality food. PRACTICAL APPLICATION: Chan seeds are presently used in a very
      limited manner as a food source; however, considering their high quality
      composition, they have the potential for a more extended use in the food
      industry.

PMID- 22132861
TI  - Effectiveness of a clinical practice guideline implementation strategy for
      patients with anxiety disorders in primary care: cluster randomized trial.
AB  - BACKGROUND: Anxiety is a common mental health problem seen in primary care.
      However, its management in clinical practice varies greatly. Clinical practice
      guidelines (CPGs) have the potential to reduce variations and improve the care
      received by patients by promoting interventions of proven benefit. However,
      uptake and adherence to their recommendations can be low. METHOD/DESIGN: This
      study involves a community based on cluster randomized trial in primary
      healthcare centres in the Madrid Region (Spain). The project aims to determine
      whether the use of implementation strategy (including training session,
      information, opinion leader, reminders, audit, and feed-back) of CPG for patients
      with anxiety disorders in primary care is more effective than usual diffusion.
      The number of patients required is 296 (148 in each arm), all older than 18 years
      and diagnosed with generalized anxiety disorder, panic disorder, and panic
      attacks by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV).
      They are chosen by consecutive sampling. The main outcome variable is the change
      in two or more points into Goldberg anxiety scale at six and twelve months.
      Secondary outcome variables include quality of life (EuroQol 5D), and degree of
      compliance with the CPG recommendations on treatment, information, and referrals
      to mental health services. Main effectiveness will be analyzed by comparing the
      patients percentage improvement on the Goldberg scale between the intervention
      group and the control group. Logistic regression with random effects will be used
      to adjust for prognostic factors. Confounding factors or factors that might alter
      the effect recorded will be taken into account in this analysis. DISCUSSION:
      There is a need to identify effective implementation strategies for CPG for the
      management of anxiety disorders present in primary care. Ensuring the appropriate
      uptake of guideline recommendations can reduce clinical variation and improve the
      care patients receive. TRIAL REGISTRATION: ISRCTN: ISRCTN83365316.

PMID- 22132862
TI  - Breast cancer and menopause: perceptions of diagnosis, menopausal therapies and
      health behaviors.
AB  - OBJECTIVES: The aim of this study was to investigate the perception and
      experience of menopause diagnosis and therapies, the information provided and
      health behaviors in younger women with breast cancer. METHODS: The questionnaire
      study was completed by 114 women, aged 40-51 years, with non-metastatic breast
      cancer. Women were recruited from outpatient clinics and the community.
      Descriptive statistics were completed. RESULTS: Most women were satisfied with
      the manner in which they were informed of the breast cancer (69%) and the
      menopause (59%) diagnoses. Although 80% of women were given breast cancer
      information, only 54% were given menopause information at diagnosis. Women were
      least satisfied (26%) with information regarding the long-term complications of
      menopause. Women perceived exercise (68%) and improving lifestyle (61%) as most
      effective in alleviating symptoms of menopause. The majority of women reported
      that they did not understand the risks/benefits of 'bioidentical' hormones (79%)
      and herbal therapies (78%), while 58% perceived hormone replacement therapies as
      associated with an increased risk of breast cancer. Most women reported weight
      gain (68%) and osteoporosis (67%) as the most common problems/fears regarding
      menopause. However, regarding health behaviors, only 56% reported having relevant
      tests including a blood sugar test or a bone density test. CONCLUSION: While
      information needs regarding breast cancer appear well met in younger women, unmet
      information needs regarding menopause after breast cancer persist. Further
      education and support are required for these women to optimize health screening
      and prevention behaviors and to ensure informed decision-making regarding
      menopause treatment options.

PMID- 22132863
TI  - Antimutagenic and free radical scavenger effects of leaf extracts from Accacia
      salicina.
AB  - BACKGROUND: Three extracts were prepared from the leaves of Accacia salicina;
      ethyl acetate (EA), chloroform (Chl) and petroleum ether (PE) extracts and was
      designed to examine antimutagenic, antioxidant potenty and oxidative DNA damage
      protecting activity. METHODS: Antioxidant activity of A. salicina extracts was
      determined by the ability of each extract to protect against plasmid DNA strand
      scission induced by hydroxyl radicals. An assay for the ability of these extracts
      to prevent mutations induced by various oxidants in Salmonella typhimurium TA102
      and TA 104 strains was conducted. In addition, nonenzymatic methods were employed
      to evaluate anti-oxidative effects of tested extracts. RESULTS: These extracts
      from leaf parts of A. salicina showed no mutagenicity either with or without the
      metabolic enzyme preparation (S9). The highest protections against
      methylmethanesulfonate induced mutagenicity were observed with all extracts and
      especially chloroform extract. This extract exhibited the highest inhibitiory
      level of the Ames response induced by the indirect mutagen 2- aminoanthracene.
      All extracts exhibited the highest ability to protect plasmid DNA against
      hydroxyl radicals induced DNA damages. The ethyl acetate (EA) and chloroform
      (Chl) extracts showed with high TEAC values radical of 0.95 and 0.81 mM
      respectively, against the ABTS(.+). CONCLUSION: The present study revealed the
      antimutagenic and antioxidant potenty of plant extract from Accacia salicina
      leaves.

PMID- 22132864
TI  - Atrial selective effect of amiodarone to increase threshold of excitation.
AB  - Increases of pacing threshold stimulation are well documented with different
      antiarrhythmic drugs, but not with amiodarone. We report a case of a patient with
      dual-chamber pacing, with stable thresholds on repeated measurements on the last
      year, who presented severe increase of atrial pacing threshold resulting in loss
      of atrial capture after a year of treatment with amiodarone. Thresholds were
      normalized once amiodarone was removed. Ventricular thresholds were not affected.

PMID- 22132865
TI  - Does empty zona pellucida indicate poor ovarian response on intra cytoplasmic
      sperm injection cycles?
AB  - The factors behind the empty zona pellucida (EZP) formation and its relationship
      with in vitro fertilization (IVF) outcomes were analyzed. A total of 104 patients
      who underwent IVF treatment and collected oocytes including EZP were enrolled in
      this study. EZP index (EZPI = the ratio of number of EZP to number of cumulus
      oocyte complex (COC)) was used for the statistical analysis. Patients were
      grouped as Group 1 when EZPI <= 0.17 (n = 57) and Group 2 when EZPI > 0.17 (n =
      47). Type-2 EZP, a variation or an advanced type of oocyte degeneration, is
      tested. Woman age, basal hormone levels, and total gonadotropin dose were
      significantly higher in Group 2 compared to Group 1. Total antral follicle count
      was significantly low in Group 2. Total number of mature oocytes, oocyte quality
      index, the number of fertilized oocytes, and the numbers of Grade 1 embryos were
      significantly low in Group 2. On the linear regression analysis, using
      gonadotropin releasing hormone antagonist protocol (B = 0.086, p = 0.030), the
      number of >=17 mm follicle (B = 0.015, p = 0.047), peak serum level of estradiol
      (B = -3.625; p = 0.014), number of fertilized oocytes (B = -0.02, p = 0.0001) and
      the day-2 embryo score (B = -0,044, p = 0.001) significantly affected EZPI. An
      increment of the EZPI may be revealed decreased oocyte quality, and it is also
      related to the poor ovarian response.

PMID- 22132867
TI  - Toxin-assisted micropredation: experimental evidence shows that contact
      micropredation rather than exotoxicity is the role of Prymnesium toxins.
AB  - Blooms of Prymnesium parvum can severely harm fish and zooplankton, presumably
      through the release of allelopathic exotoxins that offer advantages for
      Prymnesium in its interactions with competitors and prey. We show that Prymnesium
      attaches to zooplankton and fish, causing mortality, whereas exposure of these
      organisms to Prymnesium across a permeable membrane does not cause mortality. We
      also show that Prymnesium exotoxins are released independently of contact
      toxicity only in response to experimental procedures or natural causes of stress.
      Our results are consistent with the idea that toxins have evolved for release
      during cell-to-cell contact in support of heterotrophy. The evolution of toxin
      assisted micropredation would be consistent with mechanisms of natural selection
      favouring individual fitness as opposed to broadcast allelopathy from which the
      benefits are more dispersed. Research into the toxicity of Prymnesium and other
      harmful algal species may profit from focus on processes following physical
      contact with potential prey.

PMID- 22132866
TI  - Molecular phylodynamics and protein modeling of infectious salmon anemia virus
      (ISAV).
AB  - BACKGROUND: ISAV is a member of the Orthomyxoviridae family that affects
      salmonids with disastrous results. It was first detected in 1984 in Norway and
      from then on it has been reported in Canada, United States, Scotland and the
      Faroe Islands. Recently, an outbreak was recorded in Chile with negative
      consequences for the local fishing industry. However, few studies have examined
      available data to test hypotheses associated with the phylogeographic
      partitioning of the infecting viral population, the population dynamics, or the
      evolutionary rates and demographic history of ISAV. To explore these issues, we
      collected relevant sequences of genes coding for both surface proteins from
      Chile, Canada, and Norway. We addressed questions regarding their phylogenetic
      relationships, evolutionary rates, and demographic history using modern
      phylogenetic methods. RESULTS: A recombination breakpoint was consistently
      detected in the Hemagglutinin-Esterase (he) gene at either side of the Highly
      Polymorphic Region (HPR), whereas no recombination breakpoints were detected in
      Fusion protein (f) gene. Evolutionary relationships of ISAV revealed the 2007
      Chilean outbreak group as a monophyletic clade for f that has a sister
      relationship to the Norwegian isolates. Their tMRCA is consistent with
      epidemiological data and demographic history was successfully recovered showing a
      profound bottleneck with further population expansion. Finally, selection
      analyses detected ongoing diversifying selection in f and he codons associated
      with protease processing and the HPR region, respectively. CONCLUSIONS: Our
      results are consistent with the Norwegian origin hypothesis for the Chilean
      outbreak clade. In particular, ISAV HPR0 genotype is not the ancestor of all ISAV
      strains, although SK779/06 (HPR0) shares a common ancestor with the Chilean
      outbreak clade. Our analyses suggest that ISAV shows hallmarks typical of RNA
      viruses that can be exploited in epidemiological and surveillance settings. In
      addition, we hypothesized that genetic diversity of the HPR region is governed by
      recombination, probably due to template switching and that novel fusion gene
      proteolytic sites confer a selective advantage for the isolates that carry them.
      Additionally, protein modeling allowed us to relate the results of phylogenetic
      studies with the predicted structures. This study demonstrates that phylogenetic
      methods are important tools to predict future outbreaks of ISAV and other salmon
      pathogens.

PMID- 22132868
TI  - Glycaemic control and weight 7 years after Dose Adjustment For Normal Eating
      (DAFNE) structured education in Type 1 diabetes.
AB  - AIMS: The provision of structured education is increasingly prevalent in the
      management of Type 1 diabetes. There are little long-term follow-up data from
      such programmes. We have assessed HbA(1c) and weight over a 7-year period
      following the Dose Adjustment For Normal Eating (DAFNE) structured education
      course. METHODS: We obtained annual HbA(1c) and weight data in 111 patients who
      attended the initial series of DAFNE courses in our centre from June 2002 to end
      2003 and in a matched group of 111 patients with Type 1 diabetes of similar age
      and duration of diabetes seen over the same period who had not undergone
      structured education. RESULTS: With DAFNE structured education, the mean (+/- sd)
      HbA(1c) fell from 71 +/- 12 mmol/mol (8.6 +/- 1.1%) at baseline to 65 +/- 12
      mmol/mol (8.1 +/- 1.1%) at year 1, with a subsequent rise to 67 +/- 13 mmol/mol
      (8.3 +/- 1.2%) at year 7 (P = 0.0048 vs. baseline). In the comparator group, the
      baseline HbA(1c) level was 70 +/- 14 mmol/mol (8.5 +/- 1.3%) and remained
      approximately constant during 7 years of follow-up. Weight increased by 2.4 +/-
      6.0 and 2.8 +/- 6.6 kg in the DAFNE and comparator group, respectively, during
      follow-up (not significant). CONCLUSIONS: DAFNE structured education is
      associated with an improvement in glycaemic control at 1 year, and there remains
      a persistent and clinically relevant reduction in HbA(1c) of 3 mmol/mol (0.3%)
      after 7 years. The improvement in glycaemic control after DAFNE is achieved
      without excess weight gain.

PMID- 22132869
TI  - Priming a natural or human-made environment directs attention to context
      congruent threatening stimuli.
AB  - Research suggests that attention is attracted to evolutionary threats (e.g.,
      snakes) due to an evolved "fear-module" that automatically detects biological
      threats to survival. However, recent evidence indicates that non-evolutionary
      threats (e.g., guns) capture and hold attention as well, suggesting a more
      general "threat-relevance" mechanism that directs attentional resources toward
      any potential danger in the environment. The current research measured how
      selective attentional resources were influenced both by the type of threat (e.g.,
      snake vs. gun) and by the context in which the threat was encountered.
      Participants were primed with either natural or human-made environments to assess
      how these contexts influence attention to evolutionary and non-evolutionary
      threats, as measured by a spatial-cueing task. The results indicate that whether
      biological or non-biological threats receive greater attentional processing is
      determined by the context in which they are encountered.

PMID- 22132870
TI  - Echocardiographic evaluation of cardiac structure and function in obese Egyptian
      adolescents.
AB  - OBJECTIVE: The objective of this study was to detect structural and functional
      changes in the left and right ventricles in obese Egyptian adolescents. Methods
      and results Anthropometric and echocardiographic parameters, including tissue
      Doppler imaging, were obtained from 70 obese adolescents with average body mass
      index of 34 plus or minus 3.8 and compared with 50 age- and sex-matched controls,
      with a body mass index of 21.6 plus or minus 1.9. Cardiac dimensions, stroke
      volume, left ventricular and right ventricular systolic and diastolic functions
      were evaluated. The obese group had a higher end-diastolic septal and posterior
      wall thickness and left ventricular mass index than the non-obese group. Body
      mass index, mid-arm and hip circumference values showed significant correlations
      with these echocardiographic variables. Systolic and diastolic functions of the
      left ventricle were normal in both groups, although stroke volume was high in the
      obese group. The right ventricle tissue Doppler parameters were similar in both
      groups. However, the S wave of the septal/lateral tricuspid valve annulus was
      reduced in the obese group, but not to the level reflecting systolic dysfunction.
      This was inversely correlated with hip, waist, and mid-arm circumference.
      Stepwise multiple regression analysis showed that the mid-arm and hip
      circumference followed by the body mass index are significant predictors of these
      early cardiac abnormalities. CONCLUSION: Left ventricular hypertrophy is present
      in obese children, although both systolic and diastolic functions are normal.
      Tissue Doppler imaging revealed a minor, but still significant, reduction in the
      right ventricular systolic function. Mid-arm and hip circumference are predictors
      of left ventricular hypertrophy.

PMID- 22132871
TI  - Weight gain after lymphoma treatment: fat or fiction?

PMID- 22132872
TI  - Somatic mutation of STAG2, an aneuploidy-related gene, is rare in acute
      leukemias.

PMID- 22132873
TI  - Extranodal nasal type natural killer/T-cell lymphoma of testis: report of seven
      cases with review of literature.
AB  - Seven cases of testicular extranodal natural killer (NK)/T-cell lymphoma, nasal
      type, are reported, with a literature review. Two patients had a testicular
      lesion as the initial presentation, four had a history of nasal NK/T-cell
      lymphoma and the remaining patient had concomitant involvement of an adrenal
      gland. All patients underwent orchiectomy followed by chemotherapy (CT) and/or
      radiotherapy (RT). Follow-up data showed that two patients with non-primary
      tumors died of disease within 6 and 11 months, respectively. Histologically, the
      tumor had a diffuse growth pattern largely replacing the interstitial tissues.
      Neoplastic cells showed prominent angiocentric and angioinvasive features with
      focal coagulative necrosis and apoptotic bodies. Immunohistochemically, all cases
      were positive for cytoplasmic CD3epsilon and CD56. Epstein-Barr virus infection
      was demonstrated in all cases. Testicular NK/T-cell lymphoma, whether primary or
      secondary, was generally very aggressive with a poor outcome despite
      multimodality therapy. Novel molecular therapeutic targets and more effective
      treatments are needed, especially for disseminated or recurrent cases.

PMID- 22132874
TI  - Rapid detection of FLT3 exon 20 tyrosine kinase domain mutations in patients with
      acute myeloid leukemia by high-resolution melting analysis.

PMID- 22132875
TI  - Explaining the effects of a multifaceted intervention to improve inpatient care
      in rural Kenyan hospitals--interpretation based on retrospective examination of
      data from participant observation, quantitative and qualitative studies.
AB  - BACKGROUND: We have reported the results of a cluster randomized trial of rural
      Kenyan hospitals evaluating the effects of an intervention to introduce care
      based on best-practice guidelines. In parallel work we described the context of
      the study, explored the process and perceptions of the intervention, and
      undertook a discrete study on health worker motivation because this was felt
      likely to be an important contributor to poor performance in Kenyan public sector
      hospitals. Here, we use data from these multiple studies and insights gained from
      being participants in and observers of the intervention process to provide our
      explanation of how intervention effects were achieved as part of an effort to
      better understand implementation in low-income hospital settings. METHODS:
      Initial hypotheses were generated to explain the variation in intervention
      effects across place, time, and effect measure (indicator) based on our
      understanding of theory and informed by our implementation experience and
      participant observations. All data sources available for hospitals considered as
      cases for study were then examined to determine if hypotheses were supported,
      rejected, or required modification. Data included transcriptions of interviews
      and group discussions, field notes and that from the detailed longitudinal
      quantitative investigation. Potentially useful explanatory themes were
      identified, discussed by the implementing and research team, revised, and merged
      as part of an iterative process aimed at building more generic explanatory
      theory. At the end of this process, findings were mapped against a recently
      reported comprehensive framework for implementation research. RESULTS: A
      normative re-educative intervention approach evolved that sought to reset norms
      and values concerning good practice and promote 'grass-roots' participation to
      improve delivery of correct care. Maximal effects were achieved when this
      strategy and external support supervision helped create a soft-contract with
      senior managers clarifying roles and expectations around desired performance.
      This, combined with the support of facilitators acting as an expert resource and
      'shop-floor' change agent, led to improvements in leadership, accountability, and
      resource allocation that enhanced workers' commitment and capacity and improved
      clinical microsystems. Provision of correct care was then particularly likely if
      tasks were simple and a good fit to existing professional routines. Our findings
      were in broad agreement with those defined as part of recent work articulating a
      comprehensive framework for implementation research. CONCLUSIONS: Using data from
      multiple studies can provide valuable insight into how an intervention is working
      and what factors may explain variability in effects. Findings clearly suggest
      that major intervention strategies aimed at improving child and newborn survival
      in low-income settings should go well beyond the fixed inputs (training,
      guidelines, and job aides) that are typical of many major programmes. Strategies
      required to deliver good care in low-income settings should recognize that this
      will need to be co-produced through engagement often over prolonged periods and
      as part of a directive but adaptive, participatory, information-rich, and
      reflective process.

PMID- 22132876
TI  - Highly efficient white top-emitting organic light-emitting diodes comprising
      laminated microlens films.
AB  - White top-emitting organic light-emitting diodes (OLEDs) attract much attention,
      as they are optically independent from the substrate used. While monochrome top
      emitting OLEDs can be designed easily to have high-emission efficiency, white
      light emission faces obstacles. The commonly used thin metal layers as top
      electrodes turn the device into a microresonator having detrimental narrow and
      angular dependent emission characteristics. Here we report on a novel concept to
      improve the color quality and efficiency of white top-emitting OLEDs. We laminate
      a refractive index-matched microlens film on the top-emitting device. The
      microlens film acts both as outcoupling-enhancing film and an integrating
      element, mixing the optical modes to a broadband spectrum.

PMID- 22132877
TI  - Investigation of CuInS2 thin film formation by a low-temperature chemical
      deposition method.
AB  - Copper indium disulfide (CuInS(2), CIS) thin films were prepared by an
      alternative solution-based coating process adapted from the well-established
      aqueous metal salt/thiourea precursor system. The temperature for the
      decomposition of the precursors and the formation of CIS was lowered
      significantly to 130  degrees C by using the strongly coordinating solvent
      pyridine instead of the commonly used water. In addition, the influence of
      different annealing temperatures and concentrations of thiourea (TU) in the
      precursor solution on the obtained CIS samples was investigated. The films
      possess highly beneficial properties for photovoltaic applications, showing a
      chalcopyrite crystal structure, a high optical absorption (>10(4) cm(-1)) and an
      optical band gap between 1.45 and 1.51 eV. Chemical and morphological changes
      during the thin film formation were detected and explained by time-resolved
      simultaneous grazing incident small- and wide-angle X-ray scattering (GISAXS,
      GIWAXS) measurements, scanning electron microsccopy (SEM) and simultaneous
      thermogravimetry/mass spectroscopy (TG/MS).

PMID- 22132878
TI  - Translational Mini-Review Series on B cell subsets in disease. B cells in
      multiple sclerosis: drivers of disease pathogenesis and Trojan horse for Epstein
      Barr virus entry to the central nervous system?
AB  - The recent success of therapies directed at B cells has highlighted their
      potential as central players in multiple sclerosis (MS) pathogenesis. Exciting
      new data showed that B cell depletion led to reduced clinical and magnetic
      resonance imaging (MRI) evidence of disease activity. However, the mechanisms of
      action remain unknown, but could involve autoantibody production, antigen
      presentation and/or cytokine production by B cells. Another exciting line of
      investigation in the field of MS comes from latent infection of memory B cells by
      Epstein-Barr virus (EBV). These cells are hijacked as 'Trojan horses' and
      'smuggle' the virus into the central nervous system (CNS). Thus, these new anti B
      cell treatments will also be likely to have anti-viral effects. We briefly review
      recent findings in the field of MS pathogenesis, and highlight promising new
      targets for therapeutic intervention in MS.

PMID- 22132879
TI  - Translational Mini-Review Series on B cell subsets in disease. Transitional B
      cells in systemic lupus erythematosus and Sjogren's syndrome: clinical
      implications and effects of B cell-targeted therapies.
AB  - Systemic lupus erythematosus (SLE) and Sjogren's syndrome are autoimmune
      disorders which are characterized by a disturbed B cell homeostasis which leads
      ultimately to dysfunction of various organs. One of the B cell subsets that
      appear in abnormal numbers is the population of transitional B cells, which is
      increased in the blood of patients with SLE and Sjogren's syndrome. Transitional
      B cells are newly formed B cells. In mice, transitional B cells undergo selection
      checks for unwanted specificity in the bone marrow and the spleen in order to
      eliminate autoreactive B cells from the circulating naive B cell population. In
      humans, the exact anatomical compartments and mechanisms of the specificity check
      points for transitional B cells remain unclear, but appear to be defective in SLE
      and Sjogren's syndrome. This review aims to highlight the current understanding
      of transitional B cells and their defects in the two disorders before and after B
      cell-targeted therapies.

PMID- 22132880
TI  - Translational Mini-Review Series on B cell subsets in disease. Reconstitution
      after haematopoietic stem cell transplantation - revelation of B cell
      developmental pathways and lineage phenotypes.
AB  - Haematopoietic stem cell transplantation (HSCT) is an immunological treatment
      that has been used for more than 40 years to cure a variety of diseases. The
      procedure is associated with serious side effects, due to the severe impairment
      of the immune system induced by the treatment. After a conditioning regimen with
      high-dose chemotherapy, sometimes in combination with total body irradiation,
      haematopoietic stem cells are transferred from a donor, allowing a donor-derived
      blood system to form. Here, we discuss the current knowledge of humoral problems
      and B cell development after HSCT, and relate these to the current understanding
      of human peripheral B cell development. We describe how these studies have aided
      the identification of subsets of transitional B cells and also a robust memory B
      cell phenotype.

PMID- 22132881
TI  - Immunology in the Clinic Review Series; focus on allergies: immunotherapy for
      food allergy.
AB  - There is no approved therapy for food allergy. The current standard of care is
      elimination of the triggering food from the diet and accessibility to
      epinephrine. Immunotherapy is a promising treatment approach. While
      desensitization to most foods seems feasible, it remains unclear if a permanent
      state of tolerance is achievable. The research team at Duke is pioneering
      immunotherapy for food allergies. Work here has evolved over time from small open
      label pilot studies to larger randomized designs. Our data show that
      immunological changes associated with immunotherapy include reduction in mast
      cell reactivity, decreased basophil responses, decreased specific-immunoglobulin
      (Ig)E, increased IgG4 and induction of regulatory T cells. Immunotherapy has
      generated much excitement in the food allergy community; however, further studies
      are needed before it is ready for clinical use.

PMID- 22132882
TI  - Immunology in the Clinic Review Series; focus on host responses: invariant
      natural killer T cell activation following transplantation.
AB  - Invariant natural killer T (iNKT) cells have been shown to play a key role in the
      regulation of immunity in health and disease. However, iNKT cell responses have
      also been found to influence both rejection and the induction of tolerance
      following transplantation of allogeneic cells or organs. Although a number of
      mechanisms have been identified that lead to iNKT cell activation, how iNKT cells
      are activated following transplantation remains unknown. This review will attempt
      to identify potential mechanisms of iNKT cell activation in the context of
      transplantation by applying knowledge garnered from other disease situations.
      Furthermore, we put forward a novel mechanism of iNKT cell activation which we
      believe may be the dominant mechanism responsible for iNKT activation in this
      setting, i.e. bystander activation by interleukin-2 secreted by recently
      activated conventional T cells.

PMID- 22132883
TI  - Immunology in the Clinic Review Series; focus on metabolic diseases: development
      of islet autoimmune disease in type 2 diabetes patients: potential sequelae of
      chronic inflammation.
AB  - Historically, the development of type 2 diabetes has been considered not to have
      an autoimmune component, in contrast to the autoimmune pathogenesis of type 1
      diabetes. In this review we will discuss the accumulating data supporting the
      concept that islet autoreactivity and inflammation is present in type 2 diabetes
      pathogenesis, and the islet autoimmunity appears to be one of the factors
      associated with the progressive nature of the type 2 diabetes disease process.

PMID- 22132885
TI  - Immunology in the Clinic Review Series; focus on allergies: basophils as
      biomarkers for assessing immune modulation.
AB  - Allergen-specific immunotherapy is an effective clinical treatment for
      hypersensitivity to many allergens. Studies of basophils during immunotherapy
      have provided insight into underlying immune mechanisms and support the potential
      use of basophil activation as a biomarker of clinical outcomes. This review
      examines the evidence for different pathways of basophil modulation associated
      with various forms of immunotherapy. Better understanding the molecular
      mechanisms of basophil activation and desensitization and the relationship
      between suppression of these effector cells to clinical outcomes holds promise
      for further development and improvement in potential therapies for allergic
      diseases.

PMID- 22132886
TI  - 'Insulin autoantibody affinity measurement using a single concentration of
      unlabelled insulin competitor discriminates risk in relatives of patients with
      type 1 diabetes.
AB  - Development of high-risk combinations of multiple islet autoantibodies and type 1
      diabetes is associated with high-affinity insulin autoantibodies (IAA), but IAA
      affinity measurements require large serum volumes. We therefore investigated
      whether a simplified method of IAA affinity measurement using a low concentration
      of unlabelled insulin (ULI) competitor discriminated between moderate-high- and
      low-affinity IAA and identified individuals at highest risk of disease. Samples
      were assayed by radiobinding microassay using high (4.0 * 10(-5) mol/l) and low
      (7 * 10(-9) mol/l) ULI concentrations for competitive displacement in three
      cohorts of IAA-positive individuals; (1) 68 patients with newly-diagnosed type 1
      diabetes; (2) 40 healthy schoolchildren; and (3) 114 relatives of patients with
      type 1 diabetes followed prospectively for disease development (median follow-up
      13 years). IAA results obtained with low ULI were expressed as a percentage of
      those obtained with high ULI and this was used to classify samples as low or
      moderate-high affinity (0-50% and >50%, respectively). Sixty-eight patient
      samples were positive with high and 67 (99%) with low ULI. Forty schoolchildren
      were IAA-positive with high and 22 (55%) with low ULI (P < 0.001). Of the
      relatives, 113 were positive with high and 83 (73%) with low ULI (P < 0.001). In
      relatives, moderate-high affinity IAA were associated with multiple islet
      antibodies (P < 0.001) and greater diabetes risk than low affinity IAA (P <
      0.001). A single low concentration of ULI competitor can act as a surrogate for
      complex IAA affinity measurements and identifies those IAA-positive relatives at
      highest risk of disease progression.

PMID- 22132884
TI  - Immunology in the Clinic Review Series; focus on host responses: T cell responses
      to herpes simplex viruses.
AB  - Herpes virus infections are chronic and co-exist with acquired immune responses
      that generally prevent severe damage to the host, while allowing periodic
      shedding of virus and maintenance of its transmission in the community. Herpes
      simplex viruses type 1 and 2 (HSV-1, HSV-2) are typical in this regard and are
      representative of the viral subfamily Alphaherpesvirinae, which has a tropism for
      neuronal and epithelial cells. This review will emphasize recent progress in
      decoding the physiologically important CD8(+) and CD4(+) T cell responses to HSV
      in humans. The expanding data set is discussed in the context of the search for
      an effective HSV vaccine as therapy for existing infections and to prevent new
      infections.

PMID- 22132887
TI  - Generation of anti-tumour immune response using dendritic cells pulsed with
      carbonic anhydrase IX-Acinetobacter baumannii outer membrane protein A fusion
      proteins against renal cell carcinoma.
AB  - Carbonic anhydrase IX (CA9), a specific molecular marker for renal cell carcinoma
      (RCC), serves as a potential target for RCC-specific immunotherapy using
      dendritic cells (DCs). However, pulsing of DCs with CA9 alone is not sufficient
      for generation of a therapeutic anti-tumour immune response against RCC. In this
      study, in order to generate a potent anti-tumour immune response against RCC, we
      produced recombinant CA9-Acinetobacter baumannii outer membrane protein A
      (AbOmpA) fusion proteins, designated CA9-AbOmpA, and investigated the ability of
      DCs pulsed with CA9-AbOmpA fusion proteins in a murine renal cell carcinoma
      (RENCA) model. A recombinant CA9-AbOmpA fusion protein was composed of a unique
      proteoglycan-related region of CA9 (1-120 amino acids) fused at the C-terminus
      with transmembrane domain of AbOmpA (1-200 amino acids). This fusion protein was
      capable of inducing DC maturation and interleukin (IL)-12 production in DCs.
      Interaction of DCs pulsed with CA9-AbOmpA fusion proteins with naive T cells
      stimulated secretion of IL-2, interferon (IFN)-gamma and tumour necrosis factor
      (TNF)-alpha in T cells. Lymphocytes harvested from mice immunized with DCs pulsed
      with CA9-AbOmpA fusion proteins secreted IFN-gamma and showed a specific
      cytotoxic activity against CA9-expressing RENCA (RENCA-CA9) cells. Administration
      of CA9-AbOmpA-pulsed DC vaccine suppressed growth of RENCA-CA9 cells in mice with
      an established tumour burden. These results suggest that DCs pulsed with CA9
      AbOmpA fusion proteins generate a specific anti-tumour immune response against
      RCC, which can be utilized in immunotherapy of RCC.

PMID- 22132888
TI  - Pregnancy-associated diseases are characterized by the composition of the
      systemic regulatory T cell (Treg) pool with distinct subsets of Tregs.
AB  - Dysregulations concerning the composition and function of regulatory T cells
      (T(regs)) are assumed to be involved in the pathophysiology of complicated
      pregnancies. We used six-colour flow cytometric analysis to demonstrate that the
      total CD4(+) CD127(low+/-) CD25(+) forkhead box protein 3 (FoxP3)(+) T(reg) cell
      pool contains four distinct T(reg) subsets: DR(high+) CD45RA(-), DR(low+) CD45RA(
      ), DR(-) CD45RA(-) T(regs) and naive DR(-) CD45RA(+) T(regs). During the normal
      course of pregnancy, the most prominent changes in the composition of the total
      T(reg) cell pool were observed between the 10th and 20th weeks of gestation, with
      a clear decrease in the percentage of DR(high+) CD45RA(-) and DR(low+) CD45RA(-)
      T(regs) and a clear increase in the percentage of naive DR(-) CD45RA(+) T(regs).
      After that time, the composition of the total T(reg) cell pool did not change
      significantly. Its suppressive activity remained stable during normally
      progressing pregnancy, but decreased significantly at term. Compared to healthy
      pregnancies the composition of the total T(reg) cell pool changed in the way that
      its percentage of naive DR(-) CD45RA(+) T(regs) was reduced significantly in the
      presence of pre-eclampsia and in the presence of preterm labour necessitating
      preterm delivery (PL). Interestingly, its percentage of DR(high+) CD45RA(-) and
      DR(low+) CD45RA(-) T(regs) was increased significantly in pregnancies affected by
      pre-eclampsia, while PL was accompanied by a significantly increased percentage
      of DR(-) CD45RA(-) and DR(low+) CD45RA(-) T(regs). The suppressive activity of
      the total T(reg) cell pool was diminished in both patient collectives. Hence, our
      findings propose that pre-eclampsia and PL are characterized by homeostatic
      changes in the composition of the total T(reg) pool with distinct T(reg) subsets
      that were accompanied by a significant decrease of its suppressive activity.

PMID- 22132889
TI  - Essential role of the adaptor protein Nck1 in Jurkat T cell activation and
      function.
AB  - The non-catalytic region of tyrosine kinase (Nck) is proposed to play an
      essential role in T cell activation. However, evidence based on functional and
      biochemical studies has brought into question the critical function of Nck.
      Therefore, the aim of the present work was to investigate the role of Nck in T
      cell activation. To study this, the human Jurkat T cell line was used as a model
      for human T lymphocytes. The short interfering (si) RNA targeting Nck1 gene was
      used with electroporation to knock-down Nck1 protein expression in Jurkat T
      cells. Primary human CD4 T cells were also transfected with the siRNA of Nck1.
      The results showed that decreased Nck1 protein expression did not affect the
      apoptosis of the transfected Jurkat T cells compared with control siRNA
      transfected cells and non-transfected cells. Upon CD3epsilon/CD28 stimulation,
      knock-down of Nck1 in Jurkat T cells caused a decrease in CD69 expression and in
      interleukin (IL)-2 secretion. Similarly, knock-down of Nck1 in primary CD4 T
      cells also caused decreased CD69 expression. However, no significant alterations
      of CD69 and IL-2 expression were found upon phytohaemagglutinin (PHA)/phorbol
      myristate acetate (PMA) stimulation. Knock-down of Nck1 had no effect on the
      proliferation of Jurkat T cells stimulated with either PHA or anti-T cell
      receptor (TCR) monoclonal antibody (C305). The reduced Nck1 expression in Jurkat
      cells was also associated with a reduced phosphorylation of extracellular
      regulated kinase (Erk)1 and Erk2 proteins upon CD3epsilon/CD28 stimulation. In
      conclusion, the decreased Nck1 protein in Jurkat T cells resulted in an
      impairment of TCR-CD3-mediated activation involving a defective Erk
      phosphorylation pathway.

PMID- 22132890
TI  - Patient-centred screening for primary immunodeficiency, a multi-stage diagnostic
      protocol designed for non-immunologists: 2011 update.
AB  - Members of the European Society for Immunodeficiencies (ESID) and other
      colleagues have updated the multi-stage expert-opinion-based diagnostic protocol
      for non-immunologists incorporating newly defined primary immunodeficiency
      diseases (PIDs). The protocol presented here aims to increase the awareness of
      PIDs among doctors working in different fields. Prompt identification of PID is
      important for prognosis, but this may not be an easy task. The protocol therefore
      starts from the clinical presentation of the patient. Because PIDs may present at
      all ages, this protocol is aimed at both adult and paediatric physicians. The
      multi-stage design allows cost-effective screening for PID of the large number of
      potential cases in the early phases, with more expensive tests reserved for
      definitive classification in collaboration with a specialist in the field of
      immunodeficiency at a later stage.

PMID- 22132891
TI  - Proteomics plus genomics approaches in primary immunodeficiency: the case of
      immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.
AB  - Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a rare
      syndrome due to a mutation in the forkhead box protein 3 gene (FOXP3) leading to
      an impaired regulatory T cell (T(reg) ) activity associated both with skewed T
      helper type 2 (Th2) response and autoreactive phenomena. The purpose of this
      study was to describe a combined proteomics and genomics approach to
      comprehensively evaluate clinical and immunological phenotypes of patients
      affected by IPEX. T cell receptor (TCR)-Vbeta repertoire and peripheral blood
      lymphocytes phenotype from three brothers affected by IPEX were studied by flow
      cytometry. Specific immunoglobulin (Ig)E were evaluated by means of an allergenic
      molecules microarray [immuno solid-phase allergen chip (ISAC)]. Total RNA was
      extracted and hybridized to Affymetrix oligonucleotide arrays to obtain
      quantitative gene-expression levels. No FOXP3 protein was detectable within
      CD127(-) CD25(high) CD4(+) T cells from peripheral blood. A T cell-naive
      phenotype (CD62L(+) CD45R0(-)) associated with a reduction of both CD26 and CD7
      expression and a TCR-Vbeta 8 and 22 family expansions were found. B lymphocytes
      were mainly CD5(+) (B1) cells expressing a naive phenotype (tcl1(+) CD27(-)). The
      three IPEX patients had severe food allergy and specific IgE reactivity to cow's
      milk allergens, a hen's egg allergen and a wheat allergen. Gene expression
      profile analysis revealed a dysregulation associated mainly with Th1/Th2
      pathways. The multiplexing evaluation reported in this study represents a
      comprehensive approach in the assessment of genetic conditions affecting the
      immune system such as the IPEX syndrome, paving the way for the development of
      diagnostic tools to improve the standard clinical and immunological profiling of
      the disease.

PMID- 22132892
TI  - Up-regulation of chemokine C-C ligand 2 (CCL2) and C-X-C chemokine 8 (CXCL8)
      expression by monocytes in chronic idiopathic urticaria.
AB  - The disturbed cytokine-chemokine network could play an important role in the
      onset of diseases with inflammatory processes such as chronic idiopathic
      urticaria (CIU). Our main objectives were to evaluate the relation between
      proinflammatory chemokine serum levels from CIU patients and their response to
      autologous skin test (ASST) and basophil histamine release (BHR). We also aimed
      to assess the chemokine secretion by peripheral blood mononuclear cells (PBMC)
      upon polyclonal stimulus and to evaluate chemokine C-C ligand 2/C-X-C chemokine 8
      (CCL2/CXCL8) and Toll-like receptor-4 (TLR-4) expression in monocytes. We
      observed significantly higher serum levels of the CXCL8, CXCL9, CXCL10 and CCL2
      in CIU patients compared to the healthy group, regardless of the BHR or ASST
      response. The basal secretion of CCL2 by PBMC or induced by Staphylococcus aureus
      enterotoxin A (SEA) was higher in CIU patients than in the control group, as well
      as for CXCL8 and CCL5 secretions upon phytohaemagglutinin stimulation. Also, up
      regulation of CCL2 and CXCL8 mRNA expression was found in monocytes of patients
      upon SEA stimulation. The findings showed a high responsiveness of monocytes
      through CCL2/CXCL8 expression, contributing to the creation of a proinflammatory
      environment in CIU.

PMID- 22132893
TI  - Discrimination of agonist and antagonist forms of CXCL10 in biological samples.
AB  - The ready access to commercially available multiplex assays and the importance of
      inflammation in disease pathogenesis has resulted in an abundance of studies
      aimed at identifying surrogate biomarkers for different clinically important
      questions. Establishing a link between a biomarker and disease pathogenesis,
      however, is quite complex, and in some instances this complexity is compounded by
      post-translational modifications and the use of immunoassays that do not always
      discriminate between the different forms of the same protein. Herein, we provide
      a detailed description of an assay system that has been established to
      discriminate the agonist form of CXCL10 from the NH(2) -terminal truncated form
      of the molecule generated by dipeptidylpeptidase IV (DPP4) cleavage. We
      demonstrate the utility of this assay system for monitoring agonist and
      antagonist forms of CXCL10 in culture supernatant, patient plasma and urine
      samples. Given the important role of CXCL10 in chronic inflammatory diseases and
      its suggested role as a predictive marker in managing patients with chronic
      hepatitis C, asthma, atopic dermatitis, transplantation, tuberculosis, kidney
      injury, cancer and other diseases, we believe that our method will be of general
      interest to the research and medical community.

PMID- 22132894
TI  - Inhibition of CXCL10 release by monomeric C3bi and C4b.
AB  - Cellulose acetate (CA) beads are often used for leucocyte apheresis therapy
      against inflammatory bowel disease. In order to clarify the mechanism of the anti
      inflammatory effects of CA, global analysis of the molecules generated in blood
      by the interaction with CA beads was performed in this study. An activated medium
      was collected from whole blood that had been preincubated with CA beads, and the
      effects of the CA-activated medium on leucocyte function were investigated. Fresh
      blood was stimulated with lipopolysaccharide (LPS) or interferon (IFN)-beta in
      the presence of the activated medium, and levels of chemokines and cytokines,
      including CXCL10 (IFN-inducible protein-10), and phosphorylated STAT1 (signal
      transducer and activator of transcription 1), which is known to be essential for
      CXCL10 production in leucocytes, were measured. IFN-beta- or LPS-induced CXCL10
      production, expression of CXCL10 mRNA and phosphorylation of STAT1 were
      significantly reduced in the presence of the medium pretreated with CA beads
      compared with the control without the CA bead treatment. The factors inhibiting
      CXCL10 production were identified as the C3 and C4 fragments by mass
      spectrometry. The monomeric C3bi and C4b proteins were abundant in the medium
      pretreated with CA beads. Furthermore, purified C3bi and C4b were found to
      inhibit IFN-beta-induced CXCL10 production and STAT1 phosphorylation. Thus, STAT1
      mediated CXCL10 production induced by stimulation with LPS or IFN was potently
      inhibited by monomeric C3bi and C4b generated by the interaction of blood with CA
      beads. These mechanisms mediated by monomeric C3bi and C4b may be involved in the
      anti-inflammatory effects of CA.

PMID- 22132895
TI  - A shift in the collagen V antigenic epitope leads to T helper phenotype switch
      and immune response to self-antigen leading to chronic lung allograft rejection.
AB  - Immune responses to human leucocyte antigen (HLA) and self-antigen collagen V
      (Col-V) have been proposed in the pathogenesis of chronic rejection
      (bronchiolitis obliterans syndrome, BOS) following human lung transplantation
      (LTx). In this study, we defined the role for the shift in immunodominant
      epitopes of Col-V in inducing T helper phenotype switch leading to immunity to
      Col-V and BOS. Sera and lavage from BOS(+)  LTx recipients with antibodies to Col
      V were analysed. Two years prior to BOS, patients developed antibodies to both
      Col-V,alpha1(V) and alpha2(V) chains. However, at clinical diagnosis of BOS,
      antibodies became restricted to alpha1(V). Further, lung biopsy from BOS(+)
      patients bound to antibodies to alpha1(V), indicating that these epitopes are
      exposed. Fourteen Col-V peptides [pep1-14, pep1-4 specific to alpha1(V), pep5-8
      to alpha1,2(V) and pep9-14 to alpha2(V)] which bind to HLA-DR4 and -DR7,
      demonstrated that prior to BOS, pep 6, 7, 9, 11 and 14 were immunodominant and
      induced interleukin (IL)-10. However, at BOS, the response switched to pep1, 4
      and 5 and induced interferon (IFN)-gamma and IL-17 responses, but not IL-10. The
      T helper (Th) phenotype switch is accompanied by decreased frequency of
      regulatory T cells (T(regs) ) in the lavage. LTx recipients with antibodies to
      alpha1(V) also demonstrated increased matrix metalloproteinase (MMP) activation
      with decreased MMP inhibitor, tissue inhibitor of metalloproteinase (TIMP),
      suggesting that MMP activation may play a role in the exposure of new Col-V
      antigenic epitopes. We conclude that a shift in immunodominance of self-antigenic
      determinants of Col-V results in induction of IFN-gamma and IL-17 with loss of
      tolerance leading to autoimmunity to Col-V, which leads to chronic lung allograft
      rejection.

PMID- 22132897
TI  - Men are from Mars, women are from Venus? Examining gender differences in self
      presentation on social networking sites.
AB  - Psychological research on gender differences in self-presentation has already
      revealed that women place higher priority on creating a positive self
      presentation, while men are less concerned about the image they present in face
      to-face (ftf) communication. Nowadays, with the extensive use of new media, self
      presentation is no longer so closely tied to ftf situations, but can also take
      place in the online world. Specifically, social networking sites (SNS), such as
      Facebook or MySpace, offer various features such as profile pictures, groups, and
      virtual bulletin boards with which users can create elaborated online
      representations of themselves. What remains open is whether this virtual self
      presentation on SNS is subject to gender differences. Based on studies
      emphasizing gender-related differences in Internet communication and behavior in
      general, it can be assumed that men and women have different motives regarding
      their SNS usage as well. A multimethodological study, combining results of an
      online survey and a content analysis of 106 user profiles, assessed users'
      diverse motives for participating in SNS in general, and their use of specific
      profile elements or self-presentation in particular. In this sample of StudiVZ
      users, women tend to be more likely to use SNS for comparing themselves with
      others and for searching for information. Men, on the other hand, are more likely
      to look at other people's profiles to find friends. Moreover, women tend to use
      group names for their self-presentation and prefer adding portrait photos to
      their profiles, while men choose full-body shots.

PMID- 22132896
TI  - Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease
      ischaemia-reperfusion injury in a rat syngenic kidney transplantation model.
AB  - Reperfusion injury remains one of the major problems in transplantation. Repair
      from ischaemic acute renal failure (ARF) involves stimulation of tubular
      epithelial cell proliferation. The aim of this exploratory study was to evaluate
      the effects of preconditioning donor animals with rapamycin and tacrolimus to
      prevent ischaemia-reperfusion (I/R) injury. Twelve hours before nephrectomy, the
      donor animals received immunosuppressive drugs. The animals were divided into
      four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2
      mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus
      rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia,
      the graft was transplanted. Twenty-four hours after transplant, the kidney was
      recovered for histological analysis and cytokine expression. Preconditioning
      treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen
      and creatinine compared with control [blood urea nitrogen (BUN): P < 0.001 versus
      control and creatinine: P < 0.001 versus control]. A further decrease was
      observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was
      decreased significantly in donors treated with immunosuppressants compared with
      the control group (P < 0.001 versus control). Moreover, the number of apoptotic
      nuclei in the control group was higher compared with the treated groups (P <
      0.001 versus control). Surprisingly, only rapamycin preconditioning treatment
      increased anti-apoptotic Bcl2 levels (P < 0.001). Finally, inflammatory
      cytokines, such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-6,
      showed lower levels in the graft of those animals that had been pretreated with
      rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning
      donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce
      necrosis and apoptosis in kidney I/R injury.

PMID- 22132899
TI  - Effects of copper on the post acidification of fermented milk by St.
      thermophilus.
AB  - As an initial investigation of using Cu2+ to control post acidification, the
      fermentation time, pH and the viable counts of bacteria of fermented milk during
      fermentation and storage were studied.Streptococcus thermophilus was used as the
      starter culture to ferment the whole milk. Cu2+ was added to whole milk at a
      concentration ranging from 1.25 to 20 mg/kg before fermentation. It was observed
      that increasing the concentration of Cu2+, the fermentation time of yoghurt was
      prolonged, while the post acidification of fermented milk was decreased during
      storage. The results showed that Cu2+ at the concentration of 1.25 mg/kg could
      reduce the post acidification of fermented milk effectively and showed no
      significant effect on neither the fermentation time nor the viable counts of S.
      thermophilus (P > 0.05) compared with the control sample. These findings
      indicated that Cu2+ could be used as a potential additive to inhibit the post
      acidification of yoghurt. PRACTICAL APPLICATION: Adding copper to milk has an
      effect on fermented milk products such as yoghurt. Increasing the concentration
      of Cu2+ decreased the post acidification of fermented milk. The fermentation time
      is prolonged with the increase of Cu2+ concentration. Cu2+ at 1.25 mg/kg
      exhibited inhibition on post acidification and had no significant effect on
      fermentation time and the viable counts of fermented milk.

PMID- 22132898
TI  - The relationship of oral health literacy with oral health-related quality of life
      in a multi-racial sample of low-income female caregivers.
AB  - BACKGROUND: To investigate the association between oral health literacy (OHL) and
      oral health-related quality of life (OHRQoL) and explore the racial differences
      therein among a low-income community-based group of female WIC participants.
      METHODS: Participants (N = 1,405) enrolled in the Carolina Oral Health Literacy
      (COHL) study completed the short form of the Oral Health Impact Profile Index
      (OHIP-14, a measure of OHRQoL) and REALD-30 (a word recognition literacy test).
      Socio-demographic and self-reported dental attendance data were collected via
      structured interviews. Severity (cumulative OHIP-14 score) and extent of impact
      (number of items reported fairly/very often) scores were calculated as measures
      of OHRQoL. OHL was assessed by the cumulative REALD-30 score. The association of
      OHL with OHRQoL was examined using descriptive and visual methods, and was
      quantified using Spearman's rho and zero-inflated negative binomial modeling.
      RESULTS: The study group included a substantial number of African Americans (AA =
      41%) and American Indians (AI = 20%). The sample majority had a high school
      education or less and a mean age of 26.6 years. One-third of the participants
      reported at least one oral health impact. The OHIP-14 mean severity and extent
      scores were 10.6 [95% confidence limits (CL) = 10.0, 11.2] and 1.35 (95% CL =
      1.21, 1.50), respectively. OHL scores were distributed normally with mean
      (standard deviation, SD) REALD-30 of 15.8 (5.3). OHL was weakly associated with
      OHRQoL: prevalence rho = -0.14 (95% CL = -0.20, -0.08); extent rho = -0.14 (95%
      CL = -0.19, -0.09); severity rho = -0.10 (95% CL = -0.16, -0.05). "Low" OHL
      (defined as < 13 REALD-30 score) was associated with worse OHRQoL, with increases
      in the prevalence of OHIP-14 impacts ranging from 11% for severity to 34% for
      extent. The inverse association of OHL with OHIP-14 impacts persisted in
      multivariate analysis: Problem Rate Ratio (PRR) = 0.91 (95% CL = 0.86, 0.98) for
      one SD change in OHL. Stratification by race revealed effect-measure
      modification: Whites--PRR = 1.01 (95% CL = 0.91, 1.11); AA--PRR = 0.86 (95% CL =
      0.77, 0.96). CONCLUSIONS: Although the inverse association between OHL and OHRQoL
      across the entire sample was weak, subjects in the "low" OHL group reported
      significantly more OHRQoL impacts versus those with higher literacy. Our findings
      indicate that the association between OHL and OHRQoL may be modified by race.

PMID- 22132900
TI  - Salivary cytokine profiles in primary Sjogren's syndrome differ from those in non
      Sjogren sicca in terms of TNF-alpha levels and Th-1/Th-2 ratios.
AB  - OBJECTIVES: To compare salivary cytokine profiles in patients with primary
      Sjogren's syndrome (pSS), non-SS sicca controls, and non-sicca controls, and to
      investigate whether cytokine levels are correlated with clinical parameters of
      pSS patients. METHODS: Un-stimulated whole saliva samples were obtained from pSS
      patients (n=30) classified according to the criteria of the American European
      Consensus Group. Age- and gender-matched non-SS sicca patients (n=30) and non
      sicca subjects (n=25) served as controls. Salivary IFN-gamma, TNF-alpha, IL-1, IL
      4, IL-6, IL-10, IL-12p40, and IL-17 levels were measured using a multiplex
      Luminex(r) bead-based assay. RESULTS: pSS patients and non-SS sicca controls had
      significantly lower salivary flow rates (SFRs) than non-sicca controls, and pSS
      patients showed a more profound decrease than non-SS sicca controls. In addition,
      pSS patients and non-SS sicca controls had higher levels of IFN-gamma, TNF-alpha,
      IL-1, IL-4, IL-10, IL-12p40, and IL-17 in their saliva than non-sicca controls.
      Salivary TNF-alpha levels were higher in pSS patients than in non-SS sicca
      controls. Th-1/Th-2 ratios, represented by INF-gamma/IL-4 and TNF-alpha /IL-4
      ratios, were significantly higher in pSS patients than in non-SS sicca controls.
      SFR was found to be correlated with INF-gamma/IL-4 ratio (r=0.411 p=0.024), and
      focus score to be correlated with TNF-alpha/IL-4 ratio (r=0.581, p=0.023) in pSS
      patients. CONCLUSIONS: Th-1, Th-2, and Th17 cytokine levels were found to be
      elevated in the saliva of pSS patients compared with non-sicca controls. However,
      considerable overlap was observed between the salivary cytokine levels of pSS
      patients and of non-SS sicca controls. The features that most differentiated pSS
      and non-SS sicca were higher TNF-alpha levels and Th-1/Th-2 ratios. Th-1/Th-2
      ratio was also found to be correlated with the clinical parameters of pSS.

PMID- 22132901
TI  - The complete Ac/Ds transposon family of maize.
AB  - BACKGROUND: The nonautonomous maize Ds transposons can only move in the presence
      of the autonomous element Ac. They comprise a heterogeneous group that share 11
      bp terminal inverted repeats (TIRs) and some subterminal repeats, but vary
      greatly in size and composition. Three classes of Ds elements can cause
      mutations: Ds-del, internal deletions of the 4.6-kb Ac element; Ds1, ~400-bp in
      size and sharing little homology with Ac, and Ds2, variably-sized elements
      containing about 0.5 kb from the Ac termini and unrelated internal sequences.
      Here, we analyze the entire complement of Ds-related sequences in the genome of
      the inbred B73 and ask whether additional classes of Ds-like (Ds-l) elements, not
      uncovered genetically, are mobilized by Ac. We also compare the makeup of Ds
      related sequences in two maize inbreds of different origin. RESULTS: We found 903
      elements with 11-bp Ac/Ds TIRs flanked by 8-bp target site duplications. Three
      resemble Ac, but carry small rearrangements. The others are much shorter, once
      extraneous insertions are removed. There are 331 Ds1 and 39 Ds2 elements, many of
      which are likely mobilized by Ac, and two novel classes of Ds-l elements. Ds-l3
      elements lack subterminal homology with Ac, but carry transposase gene fragments,
      and represent decaying Ac elements. There are 44 such elements in B73. Ds-l4
      elements share little similarity with Ac outside of the 11-bp TIR, have a modal
      length of ~1 kb, and carry filler DNA which, in a few cases, could be matched to
      gene fragments. Most Ds-related elements in B73 (486/903) fall in this class.
      None of the Ds-l elements tested responded to Ac. Only half of Ds insertion sites
      examined are shared between the inbreds B73 and W22. CONCLUSIONS: The majority of
      Ds-related sequences in maize correspond to Ds-l elements that do not transpose
      in the presence of Ac. Unlike actively transposing elements, many Ds-l elements
      are inserted in repetitive DNA, where they probably become methylated and begin
      to decay. The filler DNA present in most elements is occasionally captured from
      genes, a rare feature in transposons of the hAT superfamily to which Ds belongs.
      Maize inbreds of different origin are highly polymorphic in their DNA transposon
      makeup.

PMID- 22132902
TI  - Update on the management of menometrorrhagia: new surgical approaches.
AB  - Hysterectomy has traditionally been the definitive surgical approach for heavy
      menstrual bleeding. However, the more modern concept of 'save the uterus' has led
      to new surgical approaches for the treatment of heavy menstrual bleeding, based
      on second-generation endometrial destruction (ablation/resection) techniques,
      including microwave endometrial ablation, thermal balloon endometrial ablation,
      radiofrequency electrosurgery, hydrothermal ablation and cryoablation. As
      pregnancy following endometrial ablation is still possible, we proposed to
      combine endometrial ablation and sterilization with Essure((r)) micro-inserts in
      women with confirmed menometrorrhagia and the desire, or medical need, for
      permanent tubal sterilization. Although large diameter resectoscopy provides
      excellent results in the surgical treatment of myomas, the technique requires
      dilation of the cervical canal (difficult in nulliparous or menopausal patients),
      and requires general or epidural anaesthesia and, therefore, must be performed in
      an operating theatre. A major advance in terms of hysteroscopic procedures is the
      'see and treat' approach (i.e. when performing an initial diagnostic
      hysteroscopy, it is now possible to treat the pathology concurrently). Newer
      hysteroscopic techniques, often not requiring anaesthesia or analgesia, include
      OPPIuM (Office Preparation of Partially Intramural Myomas) and use of a mini
      resectoscope, allowing office diagnostic-operative hysteroscopic procedures.

PMID- 22132903
TI  - Large, single-center experience in transvenous coronary sinus lead extraction:
      procedural outcomes and predictors for mechanical dilatation.
AB  - BACKGROUND: The aim of this study was to evaluate procedural outcomes of coronary
      sinus (CS) lead extraction, focusing on predictors and need for mechanical
      dilatation (MD) in the event that manual traction (MT) is ineffective. METHODS:
      The study assessed results in 145 consecutive patients (age 69 +/- 10 years; 121
      men)--a total of 147 CS pacing leads--who underwent transvenous CS lead removal
      between January 2000 and March 2010. RESULTS: All leads but one (99%)
      (implantation time 29 +/- 25 months) were successfully removed. MT was effective
      in 103 (70%), and MD was necessary in the remaining 44 (30%) procedures. In
      multivariate analyses, unipolar design (odds ratio [OR] 3.22, 95% confidence
      interval [CI] 1.43-7.7; P = 0.005) and noninfective indication (OR 4.8, 95% CI
      1.8-13, P = 0.002) were independent predictors for MD (P < 0.0001), with a
      predictive trend for prior cardiac surgery (OR 2.2, 95% CI 0.98-5.26; P = 0.06).
      Five (3.4%) complex procedures required a transfemoral vein approach (TFA) or
      repeat procedure. No deaths occurred, and there was one major complication
      (0.7%), cardiac tamponade, after MT. No complication predictors were identified.
      CONCLUSIONS: CS leads were safely and effectively removed in nearly all patients,
      and 70% were removed with MT alone; 30% required MD. Preoperative predictors
      suggesting the need for MD or TFA were noninfective indication and unipolar lead
      design. Complications were rare, and there was no predictable pattern among MT or
      MD removal techniques.

PMID- 22132904
TI  - Changes in expression of the antioxidant enzyme SOD3 occur upon differentiation
      of human bone marrow-derived mesenchymal stem cells in vitro.
AB  - The discovery that mesenchymal stem cells (MSCs) secrete SOD3 may help explain
      studies in which MSCs have direct antioxidant activities both in vivo and in
      vitro. SOD3 is an antioxidant enzyme that dismutes toxic free radicals produced
      during inflammatory processes. Therefore, MSC production and secretion of active
      and therapeutically significant levels of SOD3 would further support the use of
      MSCs as a cellular based antioxidant therapy. The aim of this study was therefore
      to investigate in vitro if MSC differentiation down the adipogenic, chondrogenic,
      and osteogenic lineages influences the expression of the antioxidant molecule
      SOD3. Human bone marrow MSCs and their differentiated progeny were cultured under
      standard conditions and both the SOD3 gene and protein expression examined.
      Following adipogenesis, cultures demonstrated that both SOD3 protein and gene
      expression are significantly increased, and conversely, following chondrogenesis
      SOD3 protein and gene expression is significantly decreased. Following
      osteogenesis there were no significant changes in SOD3 protein or gene
      expression. This in vitro study describes the initial characterization of SOD3
      expression and secretion by differentiated MSCs. This should help guide further
      in vivo work establishing the therapeutic and antioxidative potential of MSC and
      their differentiated progeny.

PMID- 22132906
TI  - Apigenin-induced suicidal erythrocyte death.
AB  - Apigenin, a flavone in fruits and vegetables, stimulates apoptosis and thus
      counteracts cancerogenesis. Erythrocytes may similarly undergo suicidal cell
      death or eryptosis, characterized by cell shrinkage and phosphatidylserine
      exposure at the cell surface. Triggers of eryptosis include increase of cytosolic
      Ca(2+) activity ([Ca(2+)](i)), ceramide formation and ATP depletion. The present
      study explored the effect of apigenin on eryptosis. [Ca(2+)](i) was estimated
      from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine
      exposure from annexin V binding, hemolysis from hemoglobin release, ceramide
      utilizing antibodies, and cytosolic ATP with luciferin-luciferase. A 48 h
      exposure to apigenin significantly increased [Ca(2+)](i) (>= 1 MUM), increased
      ceramide formation (15 MUM), decreased ATP concentration (15 MUM), decreased
      forward scatter (>= 1 MUM), and increased annexin V binding (>= 5 MUM) but did
      not significantly modify hemolysis. The effect of 15 MUM apigenin on annexin V
      binding was blunted by Ca(2+) removal. The present observations reveal novel
      effects of apigenin, i.e. stimulation of Ca(2+) entry, ceramide formation and ATP
      depletion in erythrocytes with subsequent triggering of suicidal erythrocyte
      death, paralleled by cell shrinkage and phosphatidylserine exposure.

PMID- 22132905
TI  - An annulative electrophilic amination approach to 3-aminobenzoheteroles.
AB  - A copper-catalyzed annulative amination approach to 3-aminobenzofurans and 
      indoles from o-alkynylphenols and -anilines has been developed. The Cu-based
      catalysis is based on an umpolung, electrophilic amination with O-benzoyl
      hydroxylamines and enables the mild and convergent synthesis of various 3
      aminobenzoheteroles of biological and pharmaceutical interest. Some mechanistic
      investigations and an application of this protocol to construction of more
      complex tricyclic framework are also described.

PMID- 22132907
TI  - The influence of neighbourhood deprivation on the prevalence of diabetes in 25-
      to 74-year-old individuals: first results from the Dortmund Health Study.

PMID- 22132908
TI  - Brainstem gliomas.

PMID- 22132909
TI  - Correlation among magnetic resonance imaging findings, prognostic factors for
      survival, and histological diagnosis of intrinsic brainstem lesions in children.
AB  - OBJECT: The aim of this study was to compare MR imaging characteristics with
      histopathological findings of intrinsic brainstem lesions and also to show the
      prognostic factors in patients with diffuse brainstem glioma. METHODS: Between
      February 1988 and August 2007, 44 brainstem biopsies were performed at the Roger
      Salengro Hospital in Lille, France, in children with intrinsic brainstem lesions
      not amenable to excision. Twenty-six were female and 18 male, and the mean age
      was 6 years. RESULTS: Histological evaluation revealed diffuse brainstem glioma
      in all patients with diffuse nonenhancing brainstem lesions. Diffuse brainstem
      glioma was found in 18 patients (90%) with diffuse enhancing brainstem lesions.
      Pathological entities different from diffuse glioma were verified in 2 patients
      (10%)-1 with ependymoma and 1 with ganglioglioma. In 4 of 5 patients with a focal
      nonenhancing brainstem lesion, the histopathological diagnosis was diffuse low
      grade glioma. In 6 of 10 patients with focal enhancing brainstem lesion, the
      diagnosis was diffuse brainstem glioma, and pathological entities different from
      diffuse brainstem glioma were verified in 2 (20%), both with pilocytic
      astrocytoma. The mean 1-year actuarial survival rates for patients classified
      with low-grade and high-grade glioma were 80.4% +/- 0.08% and 48.6% +/- 0.14%,
      respectively. CONCLUSIONS: The impact of stereotactic biopsy on intrinsic
      brainstem lesions was greater in patients with MR imaging-documented enhancing
      lesions in whom the diagnosis of diffuse glioma was less frequent. Patients with
      low-grade glioma seem to have longer survival than those with high-grade glioma.

PMID- 22132910
TI  - Pathological laughter and crying in patients with pontine lesions.
AB  - Pathological laughter and crying (PLC) has been widely documented in the medical
      literature in association with various pathological processes in the brainstem,
      particularly infarction. However, it remains poorly understood. The authors
      present a case report and analyze all the cases in the literature to try to
      localize a putative faciorespiratory center. This 13-year-old girl developed a
      pontine abscess subsequent to sphenoid sinusitis. This increased in size despite
      antibiotic treatment, and she developed PLC. The abscess was then
      stereotactically aspirated, with resolution of the symptoms.   A PubMed search of
      the term "pathological laughter and crying" was performed. From these papers all
      reported cases of PLC were identified. Cases without neuroimaging were excluded.
      The remaining cases were categorized as small lesions permitting accurate
      localization within the pons, or large nonlocalizing lesions. All images of
      localizing lesions were magnified to the same size and placed on a grid. From
      this an area of maximal overlap was identified. The authors identified 7 cases of
      small localizing lesions with adequate imaging. The area of maximal overlap was
      in the region of the anterior paramedian pons. All the lesions involved this
      region of the pons. There were 28 further reports of large lesions that either
      resulted in gross compressive distortion of the pons or diffusely infiltrated it,
      and thus, although implicating involvement of a pontine center, did not allow for
      localization of a specific region of the pons.   The authors report a case of PLC
      caused by a pontine abscess. Symptoms were reversible with stereotactically
      assisted aspiration and antibiotic administration. Analysis of the lesions
      reported in the literature showed a pattern toward a regulatory center in the
      pons. The most consistently involved region was in the anterior paramedian pons,
      and this may be the site of a faciorespiratory center.

PMID- 22132911
TI  - Presurgical neuropsychological and behavioral evaluation of children with
      posterior fossa tumors.
AB  - OBJECT: Brain tumors are associated with behavioral and neuropsychological
      effects. Most available data are focused on the posttreatment neurological and
      cognitive deficits of these patients. The aim of the present study was to
      investigate the pretreatment neuropsychological and behavioral impairment in
      children with posterior fossa tumors. METHODS: The authors studied 24 children
      with posterior fossa tumors who were between 4 and 15 years of age, and who were
      surgically treated at the authors' institute. During the period prior to the
      tumor excision, neuropsychological and behavioral assessments were performed. A
      control group of age-matched children was also studied. The children's executive
      functions were assessed using the short form of the Wechsler Intelligence Scale
      for Children (WISC). For the assessment of visuospatial functions, spatial
      memory, and visuomotor integration skills, the Bender-Gestalt Test (BGT) was
      used. For assessment of the visual perception and visual memory, the authors used
      the Benton Visual Retention Test (BVRT). Furthermore, parents or caregivers
      completed the Child Behavior Checklist (CBCL). RESULTS: The WISC revealed no
      significant difference between patients and the control group. The CBCL revealed
      significant somatic concerns compared with the measure's norms. Furthermore, the
      patients differed in aggressiveness, somatic concerns, anxiety symptoms,
      internalizing of problems, and total problems. In the BGT and the BVRT results,
      no significant difference was observed between patients and the control group.
      Furthermore, no significant correlation was found between neuropsychological
      scores and sex, age at diagnosis, histological diagnosis, presence of
      hydrocephalus, degree of hydrocephalus, tumor size, and tumor location.
      CONCLUSIONS: Children with posterior fossa tumors suffer more frequently from
      somatic concerns, aggressiveness, anxiety, and internalizing disorders compared
      with controls. No difference was found with respect to intelligence scores.

PMID- 22132912
TI  - Supracerebellar infratentorial endoscopically controlled resection of pineal
      lesions: case series and operative technique.
AB  - OBJECT: The heterogeneous clinical manifestations and operative characteristics
      of pathological entities in the pineal region represent a significant challenge
      in terms of patient selection and surgical approach. Traditional surgical options
      have included endoscopic transventricular resection; open supratentorial
      microsurgical approaches through the midline, choroidal fissure, lateral
      ventricle, and tentorium; and supracerebellar infratentorial (SCIT) approaches
      through the posterior fossa. The object of the current study was to review the
      preoperative characteristics and outcomes for a cohort of patients treated purely
      via the novel endoscopically controlled SCIT approach. METHODS: A single
      institution series of 9 consecutive patients (4 male and 5 female patients [10
      total cases]; mean age 21 years, range 6-37 years) treated via the endoscopically
      controlled SCIT approach for a pathological entity in the pineal region was
      retrospectively reviewed. The mean follow-up time was 13.2 months. RESULTS: The
      endoscopically controlled SCIT approach was successfully used to approach a
      variety of pineal lesions, including pineal cysts (6 patients), epidermoid tumor,
      WHO Grade II astrocytoma (initial biopsy and recurrence), and malignant mixed
      germ cell tumor (1 patient each). Gross-total resection and/or adequate cyst
      fenestration was achieved in 8 cases. Biopsy with conservative debulking was
      performed for the single case of low-grade astrocytoma and again at the time of
      recurrence. The mean preoperative tumor and cyst volumes were 9.9 +/- 4.4 and 3.7
      +/- 3.2 cm(3), respectively. The mean operating times were 212 +/- 71 minutes for
      tumor cases and 177 +/- 72 minutes for cysts. Estimated blood loss was less than
      150 ml for all cases. A single case (pineal cyst) was converted to an open
      microsurgical approach to enhance visualization. There were no operative
      complications, as well as no documented CSF leaks, additional CSF diversion
      procedures, or air emboli. Seven patients underwent concomitant third
      ventriculostomy into the quadrigeminal cistern. At the time of the last follow-up
      evaluation, all patients had a stable or improved modified Rankin Scale score.
      CONCLUSIONS: The endoscopically controlled SCIT approach may be used for the
      biopsy and resection of appropriately selected solid tumors of the pineal region,
      in addition to the fenestration and/or resection of pineal cysts. Preoperative
      considerations include patient presentation, anticipated disease and vascularity,
      degree of local venous anatomical distortion, and selection of optimal paramedian
      trajectory.

PMID- 22132913
TI  - Deep brain stimulation in children.

PMID- 22132914
TI  - Deep brain stimulation in children: experience and technical pearls.
AB  - OBJECT: Deep brain stimulation (DBS) is an established technique for the
      treatment of several movement disorders in adults. However, the technical
      approach, complications, and results of DBS in children have not been well
      documented. METHODS: A database of DBS implantations performed at a single
      institution, prospectively established in 1998, was reviewed for patients who
      received DBS prior to the age of 18. Diagnoses, surgical technique, and
      complications were noted. Outcomes were assessed using standard rating scales of
      neurological function. RESULTS: Of 815 patients undergoing DBS implantation over
      a 12-year period, 31 were children (mean age at surgery 13.2 years old, range 4
      17 years old). Diagnoses included the following: DYT1 primary dystonia (autosomal
      dominant, Tor1ADeltaGAG mutation, 10 cases), non-DYT1 primary dystonia (3 cases),
      secondary dystonia (11 cases), neurodegeneration with brain iron accumulation
      (NBIA, 3 cases), levodopa-responsive parkinsonism (2 cases), Lesch-Nyhan disease
      (1 case), and glutaric aciduria Type 1 (1 case). Six children ages 15-17 years
      old underwent awake microelectrode-guided surgery. For 25 children operated under
      general anesthesia, the surgical technique evolved from microelectrode-guided
      surgery to image-guided surgeries using real-time intraoperative MR imaging or CT
      for lead location confirmation. Complications included 5 hardware infections, all
      in children younger than 10 years old. At 1 year after implantation, patients
      with DYT1 dystonia had a mean improvement in the Burke-Fahn-Marsden Dystonia
      Rating Scale movement subscore of 75%, while those with secondary dystonia had
      only small improvements. Outcomes in the 3 children with NBIA were disappointing.
      CONCLUSIONS: Results of DBS in children with primary and secondary dystonias were
      similar to those in adults, with excellent results for DYT1 dystonia in children
      without fixed orthopedic deformity and much more modest results in secondary
      dystonia. In contrast to reported experience in adults with NBIA, these results
      in children with NBIA were poor. Infection risk was highest in the youngest
      patients.

PMID- 22132915
TI  - The role of magnetoencephalography in children undergoing hemispherectomy.
AB  - OBJECT: Hemispherectomy is an established neurosurgical procedure for medication
      resistant epilepsy in children. Despite the effectiveness of this technique,
      there are patients who do not achieve an optimum outcome after surgery; possible
      causes of suboptimal results include the presence of bilateral independent
      epileptogenic foci. Magnetoencephalography (MEG) is an emerging tool that has
      been found to be useful in the management of lesional and nonlesional epilepsy.
      The authors analyzed the relative contribution of MEG in patient selection for
      hemispherectomy. METHODS: The medical records of children undergoing
      hemispherectomy at the Hospital for Sick Children were reviewed. Those patients
      who underwent MEG as part of the presurgical evaluation were selected. RESULTS:
      Thirteen patients were included in the study. Nine patients were boys. The mean
      age at the time of surgery was 66 months (range 10-149 months). Seizure etiology
      was Rasmussen encephalitis in 6 patients, hemimegalencephaly in 2 patients, and
      cortical dysplasia in 4 patients. In 8 patients, video-EEG and MEG results were
      consistent to localize the primary epileptogenic hemisphere. In 2 patients, video
      EEG lateralized the ictal onset, but MEG showed bilateral spikes. Two patients
      had bilateral video-EEG and MEG spikes. Engel Class I, II, and IV outcomes were
      seen in 10, 2, and 1 patients, respectively. In 2 of the patients who had an
      outcome other than Engel Class I, the MEG clusters were concentrated in the
      disconnected hemisphere. The third patient had bilateral clusters and potentially
      independent epileptogenic foci from bilateral cortical dysplasia. CONCLUSIONS:
      The presence of unilateral MEG spike waves correlated with good outcomes
      following hemispherectomy. In some cases, MEG provides information that differs
      from that obtained from video-EEG and conventional MR imaging studies. Further
      studies with a greater number of patients are needed to assess the role of MEG in
      the preoperative assessment of candidates for hemispherectomy.

PMID- 22132916
TI  - Tumoral calcinosis presenting as a deformity of the thoracic spine.
AB  - The authors describe a rare case of tumoral calcinosis (TC) of the thoracic spine
      in a 13-year-old boy with thoracic scoliosis. The patient presented with a 2-year
      history of back pain. He had no personal or family history of bone disease,
      deformity, or malignancy. Magnetic resonance imaging revealed a heterogeneously
      enhancing mass involving the T-7 vertebral body and the left pedicle. Computed
      tomography findings suggested that the mass was calcified and that this had
      resulted in scalloping of the vertebral body. The lesion was resected completely
      by using a left T-7 costotransversectomy and corpectomy. The deformity was
      corrected with placement of a vertebral body cage and pedicle screw fixation from
      T-5 to T-9. Pathological analysis of the mass demonstrated dystrophic
      calcification with marked hypercellularity and immunostaining consistent with TC.
      This represents the third reported case of vertebral TC in the pediatric
      population. Pediatric neurosurgeons should be familiar with lesions such as TC,
      which may be encountered in the elderly and in hemodialysis-dependent
      populations, and may not always require aggressive resection.

PMID- 22132917
TI  - Massive pediatric neurosurgical injuries and lessons learned following a tornado
      disaster in Alabama.
AB  - OBJECT: A large volume of patients presented to a Level I pediatric trauma center
      during and after a recent tornado disaster. Injuries of the central and
      peripheral nervous systems and the medical responses of a pediatric neurosurgical
      team are reviewed. METHODS: The clinical courses of patients who suffered
      cranial, spinal, and peripheral nerve injuries due to the tornado storm are
      reported. The clinical actions taken by the neurosurgical team during and after
      the event are reviewed and the lessons learned are discussed. RESULTS: The
      tornado storm system moved through the Tuscaloosa and Birmingham metropolitan
      areas on the early evening hours of April 27, 2011. Twenty-four patients received
      care from the neurosurgical team. A total of 11 cranial (including placement of
      an external ventricular drain), 2 spine, and 2 peripheral procedures were
      performed for the victims. Nine procedures were performed within the first 12
      hours of the event, and an additional 6 surgeries were performed in the following
      24 hours. Injuries of the peripheral nervous system often presented in a delayed
      fashion. Several key components were identified that enabled adequate
      neurosurgical care for a large influx of acute patients. CONCLUSIONS: Massive
      casualties due to tornados are rare. A well-organized physician team working with
      the hospital administration may decrease the mortality and morbidity of such
      events.

PMID- 22132918
TI  - The economic impact of ventriculoperitoneal shunt failure.
AB  - OBJECT: Detailed costs to individuals with hydrocephalus and their families as
      well as to third-party payers have not been previously described. The purpose of
      this study was to determine the primary caregiver out-of-pocket expenses and the
      third-party payer reimbursement rate associated with a shunt failure episode.
      METHODS: A retrospective study of children born between 2000 and 2005 who
      underwent initial ventriculoperitoneal (VP) shunt placement and who subsequently
      experienced a shunt failure requiring surgical intervention within 2 years of
      their initial shunt placement was conducted. Institutional reimbursement and
      demographic data from Children's Hospital of Alabama (CHA) were augmented with a
      caregiver survey of any out-of pocket expenses encountered during the shunt
      failure episode. Institutional reimbursements and caregiver out-of-pocket
      expenses were then combined to provide the cost for a shunt failure episode at
      CHA. RESULTS: For shunt failures, the median reimbursement total was $5008
      (interquartile range [IQR] $2068-$17,984), the median caregiver out-of-pocket
      expenses was $419 (IQR $251-$1112), and the median total cost was $5411 (IQR
      $2428-$18,582). Private insurance reimbursed at a median rate of $5074 (IQR $2170
      $14,852) compared with public insurance, which reimbursed at a median rate of
      $4800 (IQR $1876-$19,395). Caregivers with private insurance reported a median
      $963 (IQR $322-$1741) for out-of-pocket expenses, whereas caregivers with public
      insurance reported a median $391 (IQR $241-$554) for out-of-pocket expenses (p =
      0.017). CONCLUSIONS: This study confirmed that private insurance reimbursed at a
      higher rate, and that although patients had a shorter length of stay as compared
      with those with public insurance, their out-of-pocket expenses associated with a
      shunt failure episode were greater. However, it could not be determined if the
      significant difference in out-of-pocket expenses between those with private and
      those with public insurance was due directly to the cost of shunt failure. This
      model does not take into consideration community resources and services available
      to those with public insurance. These resources and services could offset the out
      of-pocket burden, and therefore should be considered in future cost models.

PMID- 22132919
TI  - Antibiotic-impregnated shunt systems versus standard shunt systems: a meta- and
      cost-savings analysis.
AB  - OBJECT: Infection is a serious and costly complication of CSF shunt implantation.
      Antibiotic-impregnated shunts (AISs) were introduced almost 10 years ago, but
      reports on their ability to decrease the infection rate have been mixed. The
      authors conducted a meta-analysis assessing the extent to which AISs reduce the
      rate of shunt infection compared with standard shunts (SSs). They also examined
      cost savings to determine the degree to which AISs could decrease infection
      related hospital expenses. METHODS: After conducting a comprehensive search of
      multiple electronic databases to identify studies that evaluated shunt type and
      used shunt-related infection as the primary outcome, 2 reviewers independently
      evaluated study quality based on preestablished criteria and extracted data. A
      random effects meta-analysis of eligible studies was then performed. For studies
      that demonstrated a positive effect with the AIS, a cost-savings analysis was
      conducted by calculating the number of implanted shunts needed to prevent a shunt
      infection, assuming an additional cost of $400 per AIS system and $50,000 to
      treat a shunt infection. RESULTS: Thirteen prospective or retrospective
      controlled cohort studies provided Level III evidence, and 1 prospective
      randomized study provided Level II evidence. "Shunt infection" was generally
      uniformly defined among the studies, but the availability and detail of baseline
      demographic data for the control (SS) and treatment (AIS) groups within each
      study were variable. There were 390 infections (7.0%) in 5582 procedures in the
      control group and 120 infections (3.5%) in 3467 operations in the treatment
      group, yielding a pooled absolute risk reduction (ARR) and relative risk
      reduction (RRR) of 3.5% and 50%, respectively. The meta-analysis revealed the AIS
      to be statistically protective in all studies (risk ratio = 0.46, 95% CI 0.33
      0.63) and in single-institution studies (risk ratio = 0.38, 95% CI 0.25-0.58).
      There was some evidence of heterogeneity when studies were analyzed together (p =
      0.093), but this heterogeneity was reduced when the studies were analyzed
      separately as single institution versus multiinstitutional (p > 0.10 for both
      groups). Seven studies showed the AIS to be statistically protective against
      infection with an ARR and RRR ranging from 1.7% to 14.2% and 34% to 84%,
      respectively. The number of shunt operations requiring an AIS to prevent 1 shunt
      infection ranged from 7 to 59. Assuming 200 shunt cases per year, the annual
      savings for converting from SSs to AISs ranged from $90,000 to over $1.3 million.
      CONCLUSIONS: While the authors recognized the inherent limitations in the quality
      and quantity of data available in the literature, this meta-analysis revealed a
      significant protective benefit with AIS systems, which translated into
      substantial hospital savings despite the added cost of an AIS. Using previously
      developed guidelines on treatment, the authors strongly encourage the use of AISs
      in all patients with hydrocephalus who require a shunt, particularly those at
      greatest risk for infection.

PMID- 22132920
TI  - Progression of cerebrospinal fluid cell count and differential over a treatment
      course of shunt infection.
AB  - OBJECT: The physiological reaction of CSF white blood cells (WBCs) over the
      course of treating a shunt infection is undefined. The authors speculated that
      the CSF WBC count varies with different infecting organisms in peak level and
      differential percentage of polymorphonuclear (PMN) leukocytes, lymphocytes,
      monocytes, and eosinophils. The authors hope to identify clinically useful trends
      in the progression of CSF WBCs by analyzing a large group of patients with
      successfully treated shunt infections. METHODS: The authors reviewed 105
      successfully treated cases of shunt infections at Riley Hospital for Children.
      The study dates ranged from 2000 to 2004; this represented a period prior to the
      routine use of antibiotic-impregnated shunt catheters. They analyzed the
      following organisms: coagulase-negative staphylococci, Staphylococcus aureus,
      Propionibacterium acnes, Streptococcal species, and gram-negative organisms. The
      initial CSF sample at diagnosis was analyzed, as were levels over 14 days of
      treatment. Model fitting was performed to generate curves for the expected
      progression of the WBC counts and the differential PMN leukocytes, lymphocyte,
      monocyte, and eosinophil percentages. RESULTS: Gram-negative organisms resulted
      in a higher initial (p = 0.03) and peak WBC count with a greater differential of
      PMN leukocytes compared with other organisms. Propionibacterium acnes infections
      were associated with a significantly lower WBC count and PMN leukocytes
      percentage (p = 0.02) and higher eosinophil percentage (p = 0.002) than other
      organisms. The pattern progression of the CSF WBC count and differential
      percentages was consistent for all infections. There was an initial predominance
      of PMN leukocytes, followed by a delayed peak of lymphocytes, monocytes, and
      eosinophils over a 14-day course. All values trended toward zero over the
      treatment course. CONCLUSIONS: The initial and peak levels of CSF WBCs vary with
      the infecting organisms. The CSF cell counts showed a predictable pattern during
      the treatment of shunt infection. These trends may be useful to the physician in
      clinical decision making, although there is a wide range of variability.

PMID- 22132921
TI  - Patient with Chiari malformation Type I presenting with inducible hemifacial
      weakness.
AB  - In this report, the authors describe the first known case of inducible hemifacial
      weakness in a patient with Chiari malformation Type I (CM-I). The patient was a
      14-year-old girl with a 1-year history of right facial paresis induced by
      sustained leftward head rotation. These episodes were characterized by weak
      activation of her right facial muscles with preserved eye opening and closure.
      Additionally, she had hypernasal speech, persistent headaches, and intermittent
      left arm twitching. Magnetic resonance imaging demonstrated a CM-I. A
      suboccipital craniectomy and C-1 laminectomy were performed for decompression of
      the CM-I, with duraplasty and coagulation of the pial surface of the cerebellar
      tonsils. At the 9-month follow-up, the patient's inducible hemifacial weakness
      had completely resolved. Her symptoms were thought to have resulted from the CM
      I, perhaps due to traction on the right facial nerve by the ectopic tonsils with
      head rotation.

PMID- 22132922
TI  - Intercavernous connection between the internal carotid arteries.
AB  - Intercavernous communication between the left and right internal carotid arteries
      is an uncommon entity. The authors report a case involving a pediatric patient
      who was found to have such a vascular anomaly. Such variations should be known by
      the neurosurgeon so as to avoid misdiagnosis and potential iatrogenic injury.

PMID- 22132924
TI  - Cerebrospinal fluid pathways from cisterns to ventricles in N-butyl cyanoacrylate
      induced hydrocephalic rats.
AB  - OBJECT: Cerebrospinal fluid typically enters the subarachnoid space from the
      ventricles via the fourth ventricular foramina. However, there is clinical
      evidence that CSF also flows in the opposite direction. Ventricular reflux of CSF
      from a cistern is a well-known phenomenon in radioisotope studies in patients
      with normal-pressure hydrocephalus. Additionally, the presence of ventricular
      blood in acute subarachnoid hemorrhage is frequently observed. The goal of this
      investigation was to examine the potential CSF pathways from cisterns to
      ventricles. The authors examined pathways in rat models in which they occluded
      the fourth ventricular outlets and injected a tracer into the subarachnoid space.
      METHODS: The model for acute obstructive hydrocephalus was induced using N-butyl
      cyanoacrylate (NBCA) in 10 Sprague-Dawley rats. After 3 days, cationized ferritin
      was infused into the lumbar subarachnoid space to highlight retrograde CSF flow
      pathways. The animals were sacrificed at 48 hours, and the brains were prepared.
      The CSF flow pathway was traced by staining the ferritin with ferrocyanide.
      RESULTS: Ferritin was observed in the third ventricle in 7 of 8 rats with
      hydrocephalus and in the temporal horn of the lateral ventricles in 4 of 8 rats
      with hydrocephalus. There was no definite staining in the aqueduct, which
      suggests that the ventricular reflux originated from routes other than through
      the fourth ventricular outlets. CONCLUSIONS: The interfaces between the
      quadrigeminal cistern and third ventricle and those between the ambient cistern
      and lateral ventricle appear to be potential sites of CSF reflux from cisterns to
      ventricles in obstructive hydrocephalus.

PMID- 22132923
TI  - Tandem insults of prenatal ischemia plus postnatal raised intrathoracic pressure
      in a novel rat model of encephalopathy of prematurity.
AB  - OBJECT: Encephalopathy of prematurity (EP) is common in preterm, low birth weight
      infants who require postnatal mechanical ventilation. The worst types of EP are
      the hemorrhagic forms, including choroid plexus, germinal matrix,
      periventricular, and intraventricular hemorrhages. Survivors exhibit life-long
      cognitive, behavioral, and motor abnormalities. Available preclinical models do
      not fully recapitulate the salient features of hemorrhagic EP encountered in
      humans. In this study, the authors evaluated a novel model using rats that
      featured tandem insults of transient prenatal intrauterine ischemia (IUI) plus
      transient postnatal raised intrathoracic pressure (RIP). METHODS: Timed-pregnant
      Wistar rats were anesthetized and underwent laparotomy on embryonic Day 19.
      Intrauterine ischemia was induced by clamping the uterine and ovarian vasculature
      for 20 minutes. Natural birth occurred on embryonic Day 22. Six hours after
      birth, the pups were subjected to an episode of RIP, induced by injecting
      glycerol (50%, 13 MUl/g intraperitoneally). Control groups included naive, sham
      surgery, and IUI alone. Pathological, histological, and behavioral analyses were
      performed on pups up to postnatal Day 52. RESULTS: Compared with controls, pups
      subjected to IUI+RIP exhibited significant increases in postnatal mortality and
      hemorrhages in the choroid plexus, germinal matrix, and periventricular tissues
      as well as intraventricularly. On postnatal Days 35-52, they exhibited
      significant abnormalities involving complex vestibulomotor function and rapid
      spatial learning. On postnatal Day 52, the brain and body mass were significantly
      reduced. CONCLUSIONS: Tandem insults of IUI plus postnatal RIP recapitulate many
      features of the hemorrhagic forms of EP found in humans, suggesting that these
      insults in combination may play important roles in pathogenesis.

PMID- 22132925
TI  - Harvey Cushing and "birth hemorrhage": early pediatric neurosurgery at The Johns
      Hopkins Hospital.
AB  - Of Harvey Cushing's many contributions to neurosurgery, one of the least
      documented is his early surgical intervention in children and his pioneering
      efforts to establish pediatric neurosurgery as a subspecialty. Between 1896 and
      1912 Cushing conducted nearly 200 operations in children at The Johns Hopkins
      Hospital. A review of his records suggests that the advances he made in
      neurosurgery were significantly influenced by his experience with children. In
      this historical article, the authors describe Cushing's treatment of 6 children,
      in all of whom Cushing established a diagnosis of "birth hemorrhage." By
      reviewing Cushing's operative indications, techniques, and outcomes, the authors
      aim to understand the philosophy of his pediatric neurosurgical management and
      how this informed his development of neurosurgery as a new specialty.

PMID- 22132926
TI  - Are natural orifice transluminal endoscopic surgery and single-incision surgery
      viable techniques for cholecystectomy?
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) and single
      incision surgery (SIS) are less invasive alternatives to traditional laparoscopic
      techniques. Concerns exist over the safety of these new approaches, and
      randomized controlled trials have yet to confirm a net benefit. If NOTES and SIS
      techniques are to become standard practice, then they should be shown to be safe
      and hold clear benefits to patients. We aim at comparing the available results by
      using these techniques in a standard laparoscopic operation (cholecystectomy).
      METHODS: A systematic review using available databases (MEDLINE, EMBASE, and the
      Cochrane Controlled Trials Register) and the published English language medical
      literature was performed. All the archived articles were cross-referenced.
      Outcome data obtained from a Cochrane review of laparoscopic cholecystectomy were
      used as the control group. All the operations performed via a single incision
      were grouped under SIS, and operations in which a natural orifice (alone or as a
      hybrid technique) was analyzed, under NOTES group. Mortality and complications
      were the primary outcome measures. RESULTS: One hundred thirty-five papers
      including 4703 patients (714 NOTES, 3989 SIS) were selected for analysis. Overall
      complication rate was 4.2% in the NOTES group versus 4.3% in the SIS group, with
      a distinct complication profile. No mortality was reported in either group. NOTES
      procedures had a longer mean operative time than SIS techniques (107 versus 79
      minutes). The conversion rate between NOTES and SILS was similar (3.4% versus
      3.3%, respectively). DISCUSSION: No difference in the incidence of complications
      was observed with the newer techniques. Adequately powered randomized control
      trials are needed to clarify whether SIS/NOTES cholecystectomy has a similar
      length of hospital stay to traditional laparoscopic cholecystectomy. The
      increased occurrence of specific types of complications and their use in acute
      pathology needs further investigation to warrant further use in routine surgical
      practice.

PMID- 22132927
TI  - Electrochemical release of amine molecules from carbamate-based, electroactive
      self-assembled monolayers.
AB  - In this paper, carbamate-based self-assembled monolayers (SAMs) of
      alkanethiolates on gold were suggested as a versatile platform for release of
      amine-bearing molecules in response to the electrical signal. The designed SAMs
      underwent the electrochemical oxidation on the gold surface with simultaneous
      release of the amine molecules. The synthesis of the thiol compounds was achieved
      by coupling isocyanate-containing compounds with hydroquinone. The electroactive
      thiol was mixed with 11-mercaptoundecanol [HS(CH(2))(11)OH] to form a mixed
      monolayer, and cyclic votammetry was used for the characterization of the release
      behaviors. The mixed SAMs showed a first oxidation peak at +540 mV (versus
      Ag/AgCl reference electrode), indicating the irreversible conversion from
      carbamate to hydroquinone groups with simultaneous release of the amine
      molecules. The analysis of ToF-SIMS further indicated that the electrochemical
      reaction on the gold surface successfully released amine molecules.

PMID- 22132929
TI  - Dietary and waterborne mercury accumulation by yellow perch: a field experiment.
AB  - It is well accepted that the majority of monomethylmercury (MMHg) in fish
      originates in their food; however, the additional contribution of water as a
      source to fish MMHg levels remains unclear. We used isotope enriched mercury (Hg)
      in a controlled field experiment to quantify the uptake of Hg from ingested and
      aqueous sources by young-of-year yellow perch (Perca flavescens). Water and
      zooplankton from a lake that had received (202)Hg-enriched additions (called
      spike Hg) for 7 y during a whole-ecosystem loading study (METAALICUS) provided
      natural, low-level Hg exposure. We achieved separation of exposure pathways by
      housing perch in one of four treatments: clean water + clean food; clean water +
      Hg spiked food; Hg spiked water + clean food; Hg spiked water + Hg spiked food.
      Fish accumulated MMHg directly from water, and this source accounted for at least
      10% of MMHg in fish during the 27-d trial. Accumulation of spike Hg from water
      and food was additive, with food providing the majority of spike MMHg taken in by
      fish. Predictions from a bioenergetics model that excludes water as a source
      underestimated Hg in perch by 11%. This study illustrates the importance of
      acknowledging both food and water as sources of Hg to fish and suggests that
      aqueous Hg should be included as a source of contamination in bioaccumulation
      models and experiments.

PMID- 22132928
TI  - Neurocognitive effects of HIV, hepatitis C, and substance use history.
AB  - HIV-associated neurocognitive dysfunction persists in the highly active
      antiretroviral therapy (HAART) era and may be exacerbated by comorbidities,
      including substance use and hepatitis C virus (HCV) infection. However, the
      neurocognitive impact of HIV, HCV, and substance use in the HAART era is still
      not well understood. In the current study, 115 HIV-infected and 72 HIV
      seronegative individuals with significant rates of lifetime substance dependence
      and HCV infection received comprehensive neuropsychological assessment. We
      examined the effects of HIV serostatus, HCV infection, and substance use history
      on neurocognitive functioning. We also examined relationships between HIV disease
      measures (current and nadir CD4, HIV RNA, duration of infection) and cognitive
      functioning. Approximately half of HIV-infected participants exhibited
      neurocognitive impairment. Detectable HIV RNA but not HIV serostatus was
      significantly associated with cognitive functioning. HCV was among the factors
      most consistently associated with poorer neurocognitive performance across
      domains, while substance use was less strongly associated with cognitive
      performance. The results suggest that neurocognitive impairment continues to
      occur in HIV-infected individuals in association with poor virologic control and
      comorbid conditions, particularly HCV coinfection.

PMID- 22132931
TI  - Supercritical hydrothermal synthesis and in situ organic modification of indium
      tin oxide nanoparticles using continuous-flow reaction system.
AB  - ITO nanoparticles were synthesized hydrothermally and surface modified in
      supercritical water using a continuous flow reaction system. The organic
      modification of the nanoparticles converted the surface from hydrophilic to
      hydrophobic, making the modified nanoparticles easily dispersible in organic
      solvent. The addition of a surface modifier into the reaction system impacted the
      crystal growth and particle size as well as dispersion. The particle size was 18
      nm. Highly crystalline cubic ITO with a narrow particle size distribution was
      obtained. The advantages of short reaction time and the use of a continuous
      reaction system make this method suitable for industrial scale synthesis.

PMID- 22132930
TI  - 'Communicate to vaccinate' (COMMVAC). building evidence for improving
      communication about childhood vaccinations in low- and middle-income countries:
      protocol for a programme of research.
AB  - BACKGROUND: Effective provider-parent communication can improve childhood
      vaccination uptake and strengthen immunisation services in low- and middle-income
      countries (LMICs). Building capacity to improve communication strategies has been
      neglected. Rigorous research exists but is not readily found or applicable to
      LMICs, making it difficult for policy makers to use it to inform vaccination
      policies and practice.The aim of this project is to build research knowledge and
      capacity to use evidence-based strategies for improving communication about
      childhood vaccinations with parents and communities in LMICs. METHODS AND DESIGN:
      This project is a mixed methods study with six sub-studies. In sub-study one, we
      will develop a systematic map of provider-parent communication interventions for
      childhood vaccinations by screening and extracting data from relevant literature.
      This map will inform sub-study two, in which we will develop a taxonomy of
      interventions to improve provider-parent communication around childhood
      vaccination. In sub-study three, the taxonomy will be populated with trial
      citations to create an evidence map, which will also identify how evidence is
      linked to communication barriers regarding vaccination. In the project's fourth
      sub-study, we will present the interventions map, taxonomy, and evidence map to
      international stakeholders to identify high-priority topics for systematic
      reviews of interventions to improve parent-provider communication for childhood
      vaccination. We will produce systematic reviews of the effects of high-priority
      interventions in the fifth sub-study. In the sixth and final sub-study of the
      project, evidence from the systematic reviews will be translated into accessible
      formats and messages for dissemination to LMICs. DISCUSSION: This project
      combines evidence mapping, conceptual and taxonomy development, priority setting,
      systematic reviews, and knowledge transfer. It will build and share concepts,
      terms, evidence, and resources to aid the development of communication strategies
      for effective vaccination programmes in LMICs.

PMID- 22132932
TI  - Are online gamblers more at risk than offline gamblers?
AB  - OBJECTIVES: To characterize and compare sociodemographic profiles, game-play
      patterns, and level of addictive behaviors among adults who gamble online and
      those who do not, and to examine if, at the population level, online gambling is
      associated with more risky behaviors than offline gambling. METHODS: Respondents
      were 8,456 offline gamblers and 111 online gamblers who participated in a
      population-based survey conducted in the province of Quebec, in 2009. The study
      sample is representative of adult general population. RESULTS: There is an
      unequal distribution of online gambling in the population. A disproportionate
      number of men, young people, and students say they participate in online
      gambling. Poker players are overrepresented among online gamblers and gambling
      behaviors tend to be more excessive on the Internet. Compared with offline
      gamblers, online gamblers report more co-occurring risky behaviors, namely
      alcohol and cannabis use. CONCLUSION: Those who gamble online appear to be more
      at risk for gambling-related problems, but the present findings alone cannot be
      used as evidence for that conclusion. Future research designs could combine
      longitudinal data collection and multilevel analyses to provide more insight into
      the causal mechanisms associated with online gambling.

PMID- 22132933
TI  - Heat and pH stability of alkali-extractable corn arabinoxylan and its xylanase
      hydrolyzate and their viscosity behavior.
AB  - In in vitro batch fermentations, both alkali-extractable corn arabinoxylan (CAX)
      and its xylanase-hydrolyzate (CH) were utilized by human fecal microbiota and
      produced similar short chain fatty acid (SCFA) contents and desirable long
      fermentation profiles with low initial gas production. Fortification of these
      arabinoxylans into processed foods would contribute desirable dietary fiber
      benefits to humans. Heat and pH stability, as well as viscosity behavior of CAX
      and CH were investigated. Size exclusion chromatography was used to analyze the
      molecular size distribution after treatment at different pH's and heating
      temperatures for different time periods. Treated under boiling and pressure
      cooking conditions at pH 3, CAX was degraded to a smaller molecular size, whereas
      the molecular size of the CH showed only a minor decrease. CAX and CH were mostly
      stable at neutral pH, except when CAX was treated under pressure for 60 min that
      slightly lowered molecular size. At 37  degrees C, neither CAX nor CH was
      adversely affected by treatment at low or neutral pH. The viscosities of
      solutions containing 5% and 10% of CAX were 48.7 and 637.0 mPa.s, respectively
      that were higher than those of solutions containing 5% and 10% of its hydrolyzate
      at shear rate 1 s-1. The CAX solutions showed Newtonian flow behavior, whereas
      shear-thinning behavior was observed in CH solutions. In conclusion, the
      hydrolyzate of CAX has potential to be used in high fiber drinks due to its
      favorable fermentation properties, higher pH and heat stability, lower and shear
      thinning viscosity, and lighter color than the native CAX. PRACTICAL APPLICATION:
      Arabinoxylan extracted by an alkali from corn bran is a soluble fiber with a
      desirable low initial and extended fermentation property. Corn arabinoxylan
      hydrolyzate using an endoxylanase was much more stable at different levels of
      acidity and heat than the native arabinoxylan, and showed lower solution
      viscosity and shear-thinning property that indicates its potential as an
      alternative functional dietary fiber for the beverage industry.

PMID- 22132934
TI  - Effects of postharvest pulsed UV light treatment of white button mushrooms
      (Agaricus bisporus) on vitamin D2 content and quality attributes.
AB  - Pulsed UV light (PUV) was investigated as a means to rapidly increase vitamin
      D(2) (D(2)) content in fresh button mushrooms (Agaricus bisporus). D(2) was found
      to increase to over 100% RDA/serving following 3 pulses (1 s). Following 12
      pulses, D(2) began to approach a maximum concentration of 27 MUg/g DW. The D(2)
      produced with 3 pulses decreased from 11.9 to 9.05 MUg/g DW after 3 days of
      storage; however, D(2) levels remained nearly constant after this point
      throughout an 11-day shelf life study. PUV treated sliced mushrooms produced
      significantly more D(2) than whole mushrooms, and it was also observed that brown
      buttons generated significantly less D(2) than white buttons. Several quality
      attributes were assessed, and no significant differences between control and PUV
      treated mushrooms were observed. These findings suggest that PUV treatment is a
      viable method for rapidly increasing the D(2) content of fresh mushrooms without
      adversely affecting quality parameters.

PMID- 22132939
TI  - Diabetes in Greenland and its relationship with urbanization.
AB  - BACKGROUND AND AIM: Most studies show that diabetes increases with migration and
      urbanization. Previous studies from Greenland have shown inconsistent
      associations between cardiovascular risk and urbanization. Thus, the aim was to
      study the association between diabetes and urbanization among Greenland Inuit.
      METHODS: A total of 3089 adult Inuit aged 18 years and older participated in a
      geographically representative, population-based study 'Inuit Health in Transition
      Study'. The examination included a 75 g oral glucose tolerance test and
      anthropometric measurements. Information on socio-demographic characteristic and
      health behaviour was obtained by interview or questionnaire. The participants
      were categorized according to degree of urbanization into three groups based on
      current place of residence: (1) participants living in towns (> 2000
      inhabitants), (2) participants living in small towns (< 2000 inhabitants) and (3)
      participants living in villages (< 500 inhabitants). RESULTS: The total
      prevalence of diabetes was 9% of which 79% were previously unknown. Nine per cent
      had impaired glucose tolerance and 19% had impaired fasting glycaemia (IFG).
      Compared with towns, odds rations (ORs) for diabetes and impaired fasting
      glycaemia were higher in small towns [OR(diabetes) = 1.5 (1.0-2.3), OR(IFG) = 1.9
      (1.2-2.3)] and villages [OR(diabetes) = 1.2 (0.8-1.9), OR(IFG) = 1.3 (0.9-2.0)],
      whereas no association was seen for impaired glucose tolerance. The inverse
      association between urbanization and diabetes and impaired fasting glycaemia
      persisted after adjustment for relevant confounders. CONCLUSION: Diabetes and
      impaired fasting glycaemia decreased with urbanization contrary to the results of
      most studies. It appears that Greenland Inuit follow the pattern usually observed
      in industrialized countries with the highest risk of diabetes in the lower socio
      economic groups.

PMID- 22132941
TI  - Tip110 maintains expression of pluripotent factors in and pluripotency of human
      embryonic stem cells.
AB  - HIV-1 Tat-interacting protein of 110 kDa [Tip110; p110(nrb)/SART3/p110] is an RNA
      binding nuclear protein implicated in regulation of HIV-1 gene and host gene
      transcription, pre-mRNA splicing, and cancer immunology. Recently, we
      demonstrated a role for Tip110 in regulation of hematopoiesis. Here, we show that
      TIP110 is also expressed in human embryonic stem cells (hESCs) and expression was
      decreased with differentiation of these ESCs. TIP110 was found, through up- and
      down-modulation of expression of Tip110, to be important in maintaining
      pluripotent factor (NANOG, OCT4, and SOX2) expression in and pluripotency of
      hESCs, although the mechanisms involved and whether the Tip110 effects are direct
      remain to be determined.

PMID- 22132942
TI  - Altered brain activation in military personnel with one or more traumatic brain
      injuries following blast.
AB  - Explosive blast is a frequent cause of traumatic brain injury (TBI) among
      personnel deployed to Afghanistan and Iraq. Functional magnetic resonance imaging
      (fMRI) with an event-related stimulus-response compatibility task was used to
      compare 15 subjects with mild, chronic blast-related TBI with 15 subjects who had
      not experienced a TBI or blast exposure during deployment. Six TBI subjects
      reported multiple injuries. Relative to the control group, TBI subjects had
      slightly slower responses during fMRI and increased somatic complaints and
      symptoms of post-traumatic stress disorder (PTSD) and depression. A between-group
      analysis indicated greater activation during stimulus-response incompatibility in
      TBI subjects within the anterior cingulate gyrus, medial frontal cortex, and
      posterior cerebral areas involved in visual and visual-spatial functions. This
      activation pattern was more extensive after statistically controlling for
      reaction time and symptoms of PTSD and depression. There was also a negative
      relationship between symptoms of PTSD and activation within posterior brain
      regions. These results provide evidence for increased task-related activation
      following mild, blast-related TBI and additional changes associated with
      emotional symptoms. Limitations of this study include no matching for combat
      exposure and different recruitment strategies so that the control group was
      largely a community-based sample, while many TBI subjects were seeking services.

PMID- 22132940
TI  - Impact of mitral regurgitation on the outcome of patients treated with CRT-D:
      data from the InSync ICD Italian Registry.
AB  - BACKGROUND: We assessed the influence of clinically significant mitral
      regurgitation (MR) on clinical-echocardiographic response and outcome in heart
      failure (HF) patients treated with a biventricular defibrillator (cardiac
      resynchronization therapy defibrillator [CRT-D]). METHODS AND RESULTS: A total of
      659 HF patients underwent successful implantation of CRT-D and were enrolled in a
      multicenter prospective registry (median follow-up of 15 months). Following
      baseline echocardiographic evaluation, patients were stratified into two groups
      according to the severity of MR: 232 patients with more than mild MR (Group MR+:
      grade 2, 3, and 4 MR) versus 427 patients with mild (grade 1) or no functional MR
      (Group MR-). On 6- and 12-month echocardiographic evaluation, MR was seen to have
      improved in the vast majority of MR+ patients, while it remained unchanged in
      most MR- patients. On 12-month follow-up evaluation, a comparable response to CRT
      was observed in the two groups, in terms of the extent of left ventricular
      reverse remodeling and combined clinical and echocardiographic response. During
      long-term follow-up, event-free survival did not differ between MR+ and MR-
      patients, even when subpopulations of patients with ischemic heart disease and
      with dilated cardiomyopathy were analyzed separately. On multivariate analysis,
      the only independent predictor of death from any cause was the lack of beta
      blocker use. CONCLUSIONS: This observational analysis supports the use of CRT-D
      in HF patients with clinically significant MR; MR had no major influence on
      patient outcome.

PMID- 22132943
TI  - Sentinel lymph node biopsy for breast cancer patients using fluorescence
      navigation with indocyanine green.
AB  - BACKGROUND: There are various methods for detecting sentinel lymph nodes in
      breast cancer. Sentinel lymph node biopsy (SLNB) using a vital dye is a
      convenient and safe, intraoperatively preparative method to assess lymph node
      status. However, the disadvantage of the dye method is that the success rate of
      sentinel lymph node detection depend on the surgeon's skills and preoperative
      mapping of the sentinel lymph node is not feasible. Currently, a vital dye,
      radioisotope, or a combination of both is used to detect sentinel nodes. Many
      surgeons have reported successful results using either method. In this study we
      have analyzed breast lymphatic drainage pathways using indocyanine green (ICG)
      fluorescence imaging. METHODS: We examined the lymphatic courses, or lymphatic
      vessels, in the breast using ICG fluorescence imaging, and applied this method to
      SLNB in patients who underwent their first operative treatment for breast cancer
      between May 2006 and April 2008. Fluorescence images were obtained using a charge
      coupled device camera with a cut filter used as a detector, and light emitting
      diodes at 760 nm as a light source. When ICG was injected into the subareola and
      periareola, subcutaneous lymphatic vessels from the areola to the axilla became
      visible by fluorescence within a few minutes. The sentinel lymph node was then
      dissected with the help of fluorescence imaging navigation. RESULTS: The
      detection rate of sentinel nodes was 100%. 0 to 4 states of lymphatic drainage
      pathways from the areola were observed. The number of sentinel nodes was 3.41 on
      average. CONCLUSIONS: This method using indocyanine green (ICG) fluorescence
      imaging may possibly improve the detection rate of sentinel lymph nodes with high
      sensitivity and compensates for the deficiencies of other methods. The ICG
      fluorescence imaging technique enables observation of breast lymph vessels
      running in multiple directions and easily and accurately identification of
      sentinel lymph nodes. Thus, this technique can be considered useful.

PMID- 22132944
TI  - Effects of myricetin on the bioavailability of carvedilol in rats.
AB  - CONTEXT: As an inhibitor of CYP2C9, CYP2D6 and P-gp, myricetin might affect the
      bioavailability of carvedilol when myricetin and carvedilol are used
      concomitantly for the prevention or therapy of cardiovascular diseases as a
      combination therapy. However, the effect of myricetin on the pharmacokinetics of
      carvedilol has not been reported in vivo. OBJECTIVE: This study investigated the
      effects of myricetin on the pharmacokinetics of carvedilol after oral or
      intravenous administration of carvedilol in rats. MATERIALS AND METHODS:
      Carvedilol was administered orally or intravenously with or without oral
      administration of myricetin to rats. RESULTS: The effects of myricetin on P-gp,
      CYP2C9 and 2D6 activity were evaluated. Myricetin inhibited CYP2C9 and CYP2D6
      enzyme activity with IC50 of 13 and 57 MUM, respectively. In addition, myricetin
      significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR
      cells overexpressing P-gp. Compared with the control group, the AUC was
      significantly increased by 52.0-85.1%, and the C(max) was significantly increased
      by 93.1-133.4% in the presence of myricetin after oral administration of
      carvedilol. Consequently, the relative bioavailability of carvedilol was
      increased by 1.17- to 1.85-fold and the absolute bioavailability of carvedilol in
      the presence of myricetin was increased by 18.1-86.4%. T(max) was significantly
      decreased. DISCUSSION AND CONCLUSION: The enhanced oral bioavailability of
      carvedilol may result from both inhibition of CYP2C9 or CYP2D6-mediated
      metabolism and P-gp-mediated efflux of carvedilol in small intestine and/or in
      liver by myricetin rather than reducing renal elimination. Concomitant use of
      myricetin or myricetin-containing dietary supplements with carvedilol will
      require close monitoring for potential drug interactions.

PMID- 22132945
TI  - Removing arsenic from synthetic groundwater with iron electrocoagulation: an Fe
      and As K-edge EXAFS study.
AB  - Electrocoagulation (EC) using iron electrodes is a promising arsenic removal
      strategy for Bangladesh groundwater drinking supplies. EC is based on the rapid
      in situ dissolution of a sacrificial Fe(0) anode to generate iron precipitates
      with a high arsenic sorption affinity. We used X-ray absorption spectroscopy
      (XAS) to investigate the local coordination environment (<4.0 A) of Fe and As in
      EC precipitates generated in synthetic Bangladesh groundwater (SBGW). Fe and As K
      edge EXAFS spectra were found to be similar between samples regardless of the
      large range of current density (0.02, 1.1, 5.0, 100 mA/cm(2)) used to generate
      samples. Shell-by-shell fits of the Fe K-edge EXAFS spectra indicated that EC
      precipitates consist of primarily edge-sharing FeO(6) octahedra. The absence of
      corner-sharing FeO(6) octahedra implies that EC precipitates resemble nanoscale
      clusters (polymers) of edge-sharing octahedra that efficiently bind arsenic.
      Shell-by-shell fits of As K-edge EXAFS spectra show that arsenic, initially
      present as a mixture of As(III) and As(V), forms primarily binuclear, corner
      sharing As(V) surface complexes on EC precipitates. This specific coordination
      geometry prevents the formation of FeO(6) corner-sharing linkages. Phosphate and
      silicate, abundant in SBGW, likely influence the structure of EC precipitates in
      a similar way by preventing FeO(6) corner-sharing linkages. This study provides a
      better understanding of the structure, reactivity, and colloidal stability of EC
      precipitates and the behavior of arsenic during EC. The results also offer useful
      constraints for predicting arsenic remobilization during the long-term disposal
      of EC sludge.

PMID- 22132946
TI  - A ring fragmentation approach to medium-sized cyclic 2-alkynones.
AB  - Bicyclic gamma-silyloxy-beta-hydroxy-alpha-diazoketones, in which the Cbeta
      Cgamma bond is the ring fusion bond, productively fragment when treated with
      tin(IV) chloride to provide medium-sized cyclic 2-alkynones. This method provides
      good to excellent yields of 10-, 11-, and 12-membered alkynone products.

PMID- 22132947
TI  - Application of RIFLE criteria in Chinese patients with ANCA-associated renal
      vasculitis.
AB  - OBJECTIVES: Antineutrophil cytoplasmic autoantibody (ANCA) associated small
      vessel vasculitis (AASV) constitutes a group of life-threatening diseases and
      renal involvement is its most severe and common manifestation. Acute kidney
      injury (AKI) is common in patients with AASV but the value of RIFLE criteria is
      still unclear in those patients. METHODS: We performed a retrospective study on
      patients with AASV in Shanghai Ruijin Hospital from 1997 to 2008. RESULTS: A
      total of 147 ANCA-associated renal vasculitis patients were studied and 92
      developed AKI at diagnosis. According to RIFLE classification, 8 (8/147, 5.44%)
      patients had AKI-R, 15 (15/147, 10.20%) had AKI-I and 69 (69/147, 46.94%) had AKI
      F. Our results demonstrated that more hypertensive patients and higher BVAS were
      found in patients with AKI-F than those in other groups (p<0.01 and p<0.01,
      respectively). Survival rate was significantly lower among patients with advanced
      RIFLE categories during remission-induction therapy (p<0.05). Survival rate of 1
      year and total survival rate were significantly lower among patients with
      advanced RIFLE categories (p<0.01, p=0.001, respectively). Cox regression
      analysis demonstrated that advanced RIFLE categories were associated with a worse
      prognosis of the patients (OR=1.706, 95%CI: 1.262-2.307, p<0.01). The area under
      the ROC curve for mortality was 0.718 (95% CI: 0.63-0.81, p<0.001). CONCLUSIONS:
      The RILFE criteria is a valid measurement of both prognosis and progression in
      patients with AASV.

PMID- 22132949
TI  - Gout and hyperuricemia in Japan: perspectives for international research on
      purines and pyrimidines in man.
AB  - One of the best-known disorders in purine metabolism is accumulation of uric acid
      leading to gout. Gout is a lifestyle disease, which was nicely illustrated in the
      joint symposium of the Japanese Society of Gout and Nucleic Acid Metabolism and
      of the Purine and Pyrimidine Society held in February 2011 in Tokyo, Japan. The
      westernization of the Japanese diet led to an increase in hyperuricemia in
      Japanese, which subsequently boosted research in this field, as illustrated in
      this symposium. As a consequence, Japanese nucleotide research also expanded,
      leading to the development of not only new drugs for treatment of gout, but also
      for other diseases such as cancer, viral infections, and cardiovascular diseases.
      The research on inborn errors led to the identification of various genetic
      polymorphisms affecting drug metabolism, revealing differences between Asians and
      non-Asians. Such genetic differences may also affect the enzymatic properties of
      an enzyme or a transporter, necessitating specific inhibitors. This knowledge
      will help to introduce personalization of treatment. In this symposium, the
      interaction between various specialties formed an excellent basis for
      translational research between these specialties but also from the bench to the
      clinic.

PMID- 22132950
TI  - Treating hyperuricemia of gout: safety and efficacy of febuxostat and allopurinol
      in older versus younger subjects.
AB  - Despite an increasing incidence of gout in older age patients with multiple
      metabolic and cardiovascular comorbidities, there are limited data addressing
      whether currently available urate-lowering therapy is comparably effective and
      safe in older (>=65 years of age) versus younger (<65 years of age) patients. In
      this secondary analysis of data from the CONFIRMS trial, we found that among 374
      older subjects, urate-lowering therapy with approved doses of febuxostat or
      commonly prescribed doses of allopurinol was at least comparable to that in 1894
      younger subjects and was well tolerated despite high rates of renal impairment
      and cardiovascular comorbidities in the older subjects.

PMID- 22132951
TI  - Japanese guideline for the management of hyperuricemia and gout: second edition.
AB  - Gout is a urate deposition disease caused by persistent hyperuricemia. Because
      gout patients present with a variety of clinical symptoms, it is necessary to
      have a guideline for the standard management and care of gout and hyperuricemia.
      The Japanese Society of Gout and Nucleic Acid Metabolism, a scientific society
      committed to study nucleic acid metabolism and related diseases, established the
      first edition of the "Guideline for the Management of Hyperuricemia and Gout" in
      2002, and published the revised version in January 2010. This second edition is
      not only evidence based on a search of systemic literature, but also includes
      consensus levels by a Delphi exercise to determine the strength of the
      recommendations. A draft version of this guideline was reviewed by internal and
      external reviewers as well as a patient. In this guideline, key messages from
      each chapter are listed as statements together with the evidence level, consensus
      level, and strength of the recommendation. In this proceeding, several selected
      chapters on the clinical management of gout and hyperuricemia are described. We
      hope this guideline is appropriately used for the standard management and care of
      patients with hyperuricemia and gout in daily practice.

PMID- 22132952
TI  - Effects of losartan/hydrochlorothiazide on serum uric acid levels and blood
      pressure in hypertensive patients.
AB  - The effect of a mixed formulation of 50 mg losartan (LOS) and 12.5 mg
      hydrochlorothiazide (HCTZ) on blood pressure and the uric acid metabolism was
      analyzed in 73 patients who switched to this formulation from other
      antihypertensive drugs. Eight patients who switched to the formulation from the
      regular dose of renin-angiotensin (RA) inhibitor (angiotensin receptor blocker
      [ARB] or angiotensin-converting enzyme [ACE] inhibitor) only showed a significant
      decrease in blood pressure, from 156.9 +/- 14.1/88.6 +/- 9.7 mmHg to 128.3 +/-
      16.0/76.1 +/-10.7 mmHg (p = 0.007), and a significant increase in serum uric acid
      levels, from 5.2 +/- 1.1 mg/dL to 6.8 +/- 0.7 mg/dL (p = 0.02). In the other 50
      patients who switched from a combination of the regular dose of RA inhibitor and
      calcium channel blocker (CCB), their blood pressure significantly increased, from
      126.0 +/- 13.8/72.0 +/- 10.0 mmHg to 132.5 +/- 16.4/76.5 +/- 11.3 mmHg (p =
      0.02), and their serum uric acid levels also significantly increased, from 5.6 +/
      1.1 mg/dL to 6.1 +/- 1.3 mg/dL (p = 0.0002). Considering that guidelines
      recommend using antihypertensive therapies that do not lead to an increase in
      serum uric acid levels, we conclude that using the ARB/HCTZ combination is less
      suitable than the regular dose of the ARB/CCB combination due to its effect on
      hypertension and serum uric acid levels.

PMID- 22132953
TI  - Efficacy of benzbromarone in hyperuricemic patients associated with chronic
      kidney disease.
AB  - We have retrospectively evaluated the uric acid control status and renal function
      changes over a period of up to 7 years in 35 patients with renal impairment who
      had stage 3 or higher chronic kidney disease (CKD; stage 3 in 32 patients, stage
      4 in 2 patients, and stage 5 in 1 patient) associated with hyperuricemia and were
      receiving monotherapy with benzbromarone as an antihyperuricemic drug. Serum uric
      acid levels significantly decreased from 8.5 +/- 0.9 to 6.1 +/- 0.8 mg/dL at 6
      months and were subsequently controlled at less than 7.0 mg/dL in most patients.
      Most patients received benzbromarone at a dose of 25-50 mg/day, whereas 150-200
      mg/day was used in some patients with stage 4 or 5 CKD. No significant changes in
      estimated glomerular filtration rate (eGFR) from the baseline value of 46.2 +/-
      11.5 mL/minute/1.73 m(2) were found after benzbromarone therapy. Although the
      renal function impairment did not improve by reducing the serum uric acid levels
      with benzbromarone, the renal function did not deteriorate further on the
      therapy. These results suggest that benzbromarone is applicable to the management
      of hyperuricemia associated with renal impairment.

PMID- 22132954
TI  - Relationship between hyperuricemia and chronic kidney disease.
AB  - Because approximately 70% of uric acid is excreted from the kidney, hyperuricemia
      occurs when renal function deteriorates. Until now, it has not been clear if the
      hyperuricemia seen in such renal diseases plays a role in the progression of
      renal disease. However, recent clinical studies show that the serum uric acid
      value is closely associated with hypertension in hyperuricemic patients (cross
      sectional study), and also with the onset of hypertension (longitudinal study).
      Furthermore, one interesting report shows that treatment of hyperuricemia with
      allopurinol lowers blood pressure in juvenile essential hypertension patients
      with hyperuricemia. In addition, it is well known that hyperuricemia is closely
      associated with chronic kidney disease (CKD), is a risk factor for renal
      insufficiency in general populations, and is a poor prognostic factor of renal
      function in patients who also have IgA nephropathy. On the other hand, in
      intervention studies on hyperuricemia, the treatment of hyperuricemia with
      allopurinol in CKD has resulted in a fall in blood pressure and inhibition of the
      progression of renal damage. Conversely, the cessation of allopurinol treatment
      in CKD was followed by a rise in blood pressure and the development of renal
      damage. Furthermore, the rise of blood pressure and development of renal damage
      following cessation of allopurinol treatment are only seen in patients not
      receiving angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor
      blocker (ARB). This suggests that the renin angiotensin (RA) system plays an
      important role in the development of hypertension and renal damage from
      hyperuricemia.

PMID- 22132955
TI  - Comorbidities in patients with gout.
AB  - Gout is one of the most important diseases associated with hyperuricemia. Gout is
      characterized by acute monoarthritis with frequent flares. Some patients with
      gout have gouty tophi that are composed of monosodium urate crystals and
      inflammatory cells. In addition to tophi, gout is associated with various
      comorbidities such as obesity, hypertension, abnormal lipid metabolism, renal
      dysfunction, and urolithiasis. We examined the associations of the presence of
      tophi and comorbidities with demographic and disease characteristic data of gout
      patients. Subjects were 422 male patients with gout who visited our outpatient
      clinic. The patients' background data and laboratory data at the first visit were
      collected from patient records. We investigated the relationship between
      comorbidities and characteristics of patients using multiple regression models.
      The age of gout onset was 44 +/- 13 years. The duration of gout at the first
      visit was 6 +/- 8 years. Five percent of subjects had tophi. The presence of
      tophi was significantly associated with the duration of gout and maximum serum
      uric acid (SUA), indicating a close association of tophi with urate deposition.
      Reduced estimated glomerular filtration rate was associated with older age of
      onset, longer duration of gout, and higher levels of maximum SUA, indicating that
      sustained hyperuricemia relates with renal impairment of gout. Urolithiasis did
      not associate with gout duration and maximum SUA. The increased frequency of
      hypertension was associated with the duration of gout, suggesting that poor
      control of gout is one of the causes of hypertension. This study provides useful
      information for gout management and patient education.

PMID- 22132956
TI  - Investigation on hyperuricemia in children with obesity or various pediatric
      disorders.
AB  - The present study aims at investigating the frequency and characteristics of
      hyperuricemia in both obese and sick children. First, we established our own
      reference values for serum uric acid (UA), since UA values are highly dependent
      upon age. In the analysis of 328 samples consisting of six different age groups:
      <1, 1-3, 4-6, 7-9, 10-12, and 13-15 years, the mean values for UA were found to
      increase significantly with an increase of age. A significant sex difference was
      observed only in the age group of 13-15 years. Hyperuricemia was defined as the
      values over the mean value plus 2 standard deviations for each age group. Next,
      we examined the frequency of hyperuricemia in 1,687 obese children aged 6-15
      years and its relation to metabolic syndrome (MetS). A total of 328 children
      (19.4%) were found to have hyperuricemia. Among them, 98 children (29.9%) had
      MetS, whereas 197 (14.5%) out of 1,359 children without hyperuricemia had MetS.
      Finally, the frequency of hyperuricemia in sick patients was investigated using
      13,675 samples from 9,405 patients. Hyperuricemia was seen in 348 (3.7%) patients
      after excluding redundant samples. The number of patients with hyperuricemia was
      higher in males than in females. The most common disorder causing hyperuricemia
      was gastroenteritis, followed by respiratory tract infection and cardiac
      diseases. This first comprehensive study of childhood hyperuricemia is useful for
      considering its relationship with hyperuricemia and life-style-related disorders
      occurring in adulthood.

PMID- 22132957
TI  - Hyperuricemia in pediatric malignancies before treatment.
AB  - The objective of this study was to clarify the prevalence and characteristics of
      hyperuricemia in various pediatric malignancies before the initiation of
      treatment. We conducted a retrospective analysis of 119 children with various
      newly diagnosed malignancies between April 2000 and March 2010. On the basis of
      the reference values previously established in our laboratory, hyperuricemia was
      defined as uric acid (UA) levels above 2 standard deviations (s.d.) over the mean
      values at each age. Thirty-six patients (30.3%) showed hyperuricemia.
      Hyperuricemia was more common in male patients (36.8%) than in female patients
      (21.6%). The prevalence of hyperuricemia was highest in patients with lymphoma
      followed by those with acute lymphoblastic leukemia (ALL). When the study
      population was divided into hyperuricemia-negative and -positive populations,
      blood urea nitrogen, creatinine, and lactate dehydrogenase levels, and white
      blood cell counts (only in leukemia) were found to be significantly higher in the
      latter group by a univariate analysis. This study highlights useful information
      for identifying patients with malignancies at risk for tumor lysis syndrome (TLS)
      before starting chemotherapy.

PMID- 22132958
TI  - Effect of urine pH on uric acid excretion by manipulating food materials.
AB  - A potential utilization of dietary intervention for reducing hyperuricemia was
      tested by managing food materials. Within the framework of the Japanese
      Government's health promotion program, we made recipes that consisted of more
      protein-rich and less vegetable/fruit-rich materials for the acidic diet and
      others composed of less protein-rich and more vegetable/fruit-rich materials for
      the alkaline diet. We have shown that urine alkalization facilitates uric acid
      excretion. In this study, it has been clarified with simultaneous measurements of
      both serum and urine uric acid concentration that acidic diets increase serum
      uric acid together with a decrease of uric acid excretion. The ratio (R) of uric
      acid clearance/creatinine clearance was calculated. On the third experimental
      day, the relative R, referring to that of the first day for the acidic diet,
      became smaller than that for the alkaline diet, indicating that in acidic urine,
      uric acid excretion is limited by more active reabsorption, compared with that in
      alkaline urine. Taken together, we tentatively conclude that dietary intervention
      may well be the safest and the most economical way for the prevention of
      hyperuricemia.

PMID- 22132959
TI  - Urinary stone analysis in a patient with hyperuricemia to determine the mechanism
      of stone formation.
AB  - In order to determine the mechanism of urinary stone formation in patients with
      hyperuricemia, we analyzed the crystal components and matrix proteins in a
      urinary stone from such a patient. Micro-area X-ray spectrometry and infrared
      (IR) spectroscopy suggested that the outside of the stone was composed of calcium
      oxalate monohydrate (COM) and the inside of uric acid (UA). Proteomic analysis
      identified 37 and 14 proteins from the inside and outside of the stone,
      respectively, as matrix proteins. The proteins that were identified in an
      ethylenediaminetetraacetic acid (EDTA) fraction were able to bind calcium ions.
      Thus, calcium-binding proteins may play a significant role in the formation of
      urinary stones in patients with hyperuricemia.

PMID- 22132960
TI  - Safety of intradermal injection of monosodium urate crystals as a vaccine carrier
      in volunteers.
AB  - Monosodium urate (MSU) crystals are known to induce gouty arthritis, but also
      evoke specific cell immunity and work as an adjuvant by delivering several kinds
      of binding proteins, including idiotypic cancer vaccine peptides into dendritic
      cells. To investigate the potency of MSU crystals as a cancer vaccine carrier in
      vivo, this preclinical study examined whether intradermal injection of MSU
      crystals was safe for healthy adults. Subjects comprised 12 volunteers. Four
      different dose levels of MSU crystals were injected as follows: 2 MUg (n = 3), 20
      MUg (n = 3), 200 MUg (n = 3), or 2000 MUg (n = 3). At 24 hours after
      administration, documented erythema was seen around the injection site in a dose
      dependent manner, particularly in all adults with MSU dose >=200 MUg. However,
      redness was limited to the grade I level of the National Cancer Institute
      toxicity criteria. Serum uric acid levels did not show any change before and
      after injection. Moreover, neither gouty arthritis nor tophi developed in any
      volunteers, indicating that intradermal injection of MSU crystals did not induce
      systemic inflammation at the doses that evoked significant local inflammation.
      These findings suggest that intradermal injection of MSU crystals is
      fundamentally safe and should be made available for clinical trials using MSU
      crystal-conjugated cancer vaccines.

PMID- 22132961
TI  - Allopurinol enhances the activity of hypoxanthine-guanine
      phosphoribosyltransferase in inflammatory bowel disease patients during low-dose
      thiopurine therapy: preliminary data of an ongoing series.
AB  - Thiopurines are crucial in the treatment of inflammatory bowel disease. The
      phenotype of pivotal metabolic enzymes determines whether thioguanine nucleotides
      (6-TGN) are generated in clinically sufficiently high levels. The first step in
      activation of thiopurine prodrugs to 6-TGN is catalysis by hypoxanthine-guanine
      phosphoribosyltransferase (HGPRT). Often, patients exhibit a clinically
      unfavorable metabolism, leading to discontinuation of conventional thiopurine
      therapy. The combination of allopurinol and low-dose thiopurine therapy may
      optimize this variant metabolism, presumably by affecting enzyme activities. We
      performed a prospective pharmacodynamic study to determine the effect of
      combination therapy on the activity of HGPRT. The activity of HGPRT and 6-TGN
      concentrations was measured in red blood cells during thiopurine monotherapy and
      after 4 weeks of combination therapy. The activity of HGPRT was also measured
      after 12 weeks of combination therapy. From the results, we conclude that
      combination therapy increases the activity of HGPRT and subsequently 6-TGN
      concentrations.

PMID- 22132962
TI  - ABCG2 is a high-capacity urate transporter and its genetic impairment increases
      serum uric acid levels in humans.
AB  - The ATP-binding cassette, subfamily G, member 2 (ABCG2/BCRP) gene encodes a well
      known transporter, which exports various substrates including nucleotide analogs
      such as 3'-azido-3'-deoxythymidine (AZT). ABCG2 is also located in a gout
      susceptibility locus (MIM 138900) on chromosome 4q, and has recently been
      identified by genome-wide association studies to relate to serum uric acid (SUA)
      and gout. Becuase urate is structurally similar to nucleotide analogs, we
      hypothesized that ABCG2 might be a urate exporter. To demonstrate our hypothesis,
      transport assays were performed with membrane vesicles prepared from ABCG2
      overexpressing cells. Transport of estrone-3-sulfate (ES), a typical substrate of
      ABCG2, is inhibited by urate as well as AZT and ES. ATP-dependent transport of
      urate was then detected in ABCG2-expressing vesicles but not in control vesicles.
      Kinetic analysis revealed that ABCG2 is a high-capacity urate transporter that
      maintained its function even under high-urate concentration. The calculated
      parameters of ABCG2-mediated transport of urate were a Km of 8.24 +/- 1.44 mM and
      a Vmax of 6.96 +/- 0.89 nmol/min per mg of protein. Moreover, the quantitative
      trait locus (QTL) analysis performed in 739 Japanese individuals revealed that a
      dysfunctional variant of ABCG2 increased SUA as the number of minor alleles of
      the variant increased (p = 6.60 * 10(-5)). Because ABCG2 is expressed on the
      apical membrane in several tissues, including kidney, intestine, and liver, these
      findings indicate that ABCG2, a high-capacity urate exporter, has a physiological
      role of urate homeostasis in the human body through both renal and extrarenal
      urate excretion.

PMID- 22132963
TI  - Identification of ABCG2 dysfunction as a major factor contributing to gout.
AB  - The ATP-binding cassette, subfamily G, member 2 gene ABCG2/BCRP locates in a gout
      susceptibility locus (MIM 138900) on chromosome 4q. Recent genome-wide
      association studies also showed that the ABCG2 gene relates to serum uric acid
      levels and gout. Since ABCG2 is also known as a transporter of nucleotide analogs
      that are structurally similar to urate, and is an exporter that has common
      polymorphic reduced functionality variants, ABCG2 could be a urate secretion
      transporter and a gene causing gout. To find candidate mutations in ABCG2, we
      performed a mutation analysis of the ABCG2 gene in 90 Japanese patients with
      hyperuricemia and found six non-synonymous mutations. Among the variants, ATP
      dependent urate transport was reduced or eliminated in five variants, and two out
      of the five variants (Q126X and Q141K) were frequently detected in patients.
      Haplotype frequency analysis revealed that there is no simultaneous presence of
      Q126X and Q141K in one haplotype. As Q126X and Q141K are a nonfunctional and half
      functional haplotype, respectively, their genotype combinations are divided into
      four estimated functional groups. The association study with 161 male gout
      patients and 865 male controls showed that all of those who had dysfunctional
      ABCG2 had an increased risk of gout, and that a remarkable risk was observed in
      those with <=1/4 function (OR, 25.8; 95% CI, 10.3-64.6; p = 3.39 * 10(-21)). In
      2,150 Japanese individuals, the frequency of those with dysfunctional ABCG2 was
      more than 50%. Our function-based clinicogenetic analysis identified the
      combinations of dysfunctional variants of ABCG2 as a major contributing factor in
      Japanese patients with gout.

PMID- 22132964
TI  - Pathogenic GLUT9 mutations causing renal hypouricemia type 2 (RHUC2).
AB  - Renal hypouricemia (MIM 220150) is an inherited disorder characterized by low
      serum uric acid levels and has severe complications such as exercise-induced
      acute renal failure and urolithiasis. We have previously reported that
      URAT1/SLC22A12 encodes a renal urate-anion exchanger and that its mutations cause
      renal hypouricemia type 1 (RHUC1). With the large health-examination database of
      the Japan Maritime Self-Defense Force, we found two missense mutations (R198C and
      R380W) of GLUT9/SLC2A9 in hypouricemia patients. R198C and R380W occur in highly
      conserved amino acid motifs in the "sugar transport proteins signatures" that are
      observed in GLUT family transporters. The corresponding mutations in GLUT1 (R153C
      and R333W) are known to cause GLUT1 deficiency syndrome because arginine residues
      in this motif are reportedly important as the determinants of the membrane
      topology of human GLUT1. Therefore, on the basis of membrane topology, the same
      may be true of GLUT9. GLUT9 mutants showed markedly reduced urate transport in
      oocyte expression studies, which would be the result of the loss of positive
      charges in those conserved amino acid motifs. Together with previous reports on
      GLUT9 localization, our findings suggest that these GLUT9 mutations cause renal
      hypouricemia type 2 (RHUC2) by their decreased urate reabsorption on both sides
      of the renal proximal tubule cells. However, a previously reported GLUT9
      mutation, P412R, was unlikely to be pathogenic. These findings also enable us to
      propose a physiological model of the renal urate reabsorption via GLUT9 and URAT1
      and can lead to a promising therapeutic target for gout and related
      cardiovascular diseases.

PMID- 22132965
TI  - Diagnostic tests for primary renal hypouricemia.
AB  - Primary renal hypouricemia is a genetic disorder characterized by defective renal
      uric acid (UA) reabsorption with complications such as nephrolithiasis and
      exercise-induced acute renal failure. The known causes are: defects in the
      SLC22A12 gene, encoding the human urate transporter 1 (hURAT1), and also
      impairment of voltage urate transporter (URATv1), encoded by SLC2A9 (GLUT9) gene.
      Diagnosis is based on hypouricemia (<119 MUmol/L) and increased fractional
      excretion of UA (>10%). To date, the cases with mutations in hURAT1 gene have
      been reported in East Asia only. More than 100 Japanese patients have been
      described. Hypouricemia is sometimes overlooked; therefore, we have set up the
      flowchart for this disorder. The patients were selected for molecular analysis
      from 620 Czech hypouricemic patients. Secondary causes of hyperuricosuric
      hypouricemia were excluded. The estimations of (1) serum UA, (2) excretion
      fraction of UA, and (3) analysis of hURAT1 and URATv1 genes follow. Three
      transitions and one deletion (four times) in SLC22A12 gene and one nucleotide
      insertion in SLC2A9 gene in seven Czech patients were found. Three patients had
      acute renal failure and urate nephrolithiasis. In addition, five nonsynonymous
      sequence variants and three nonsynonymous sequence variants in SLC2A9 gene were
      found in two UK patients suffering from acute renal failure. Our finding of the
      defects in SLC22A12 and SLC2A9 genes gives further evidence of the causative
      genes of primary renal hypouricemia and supports their important role in
      regulation of serum urate levels in humans.

PMID- 22132966
TI  - ABCG2/BCRP dysfunction as a major cause of gout.
AB  - Recent genome-wide association studies showed that serum uric acid (SUA) levels
      relate to ABCG2/BCRP gene, which locates in a gout-susceptibility locus revealed
      by a genome-wide linkage study. Together with the ABCG2 characteristics, we
      hypothesized that ABCG2 transports urate and its dysfunction causes hyperuricemia
      and gout. Transport assays showed ATP-dependent transport of urate via ABCG2.
      Kinetic analysis revealed that ABCG2 mediates high-capacity transport of urate
      (Km: 8.24 +/- 1.44 mM) even under high-urate conditions. Mutation analysis of
      ABCG2 in 90 Japanese hyperuricemia patients detected six nonsynonymous mutations,
      including five dysfunctional variants. Two relatively frequent dysfunctional
      variants, Q126X and Q141K, were then examined. Quantitative trait locus analysis
      of 739 Japanese individuals showed that Q141K increased SUA as the number of
      minor alleles of Q141K increased (p = 6.60 * 10(-5)). Haplotype frequency
      analysis revealed that there is no simultaneous presence of Q126X and Q141K in
      one haplotype. Becuase Q126X and Q141K are assigned to nonfunctional and half
      functional haplotypes, respectively, their genotype combinations are divided into
      four functional groups. The association study with 161 male gout patients and 865
      male controls showed that all of those with dysfunctional ABCG2 increased the
      gout risk, especially those with <=1/4 function (OR, 25.8; 95% CI, 10.3-64.6; p =
      3.39 * 10(-21)). These genotypes were found in 10.1% of gout patients, but in
      only 0.9% of control. Our function-based clinicogenetic (FBCG) analysis showed
      that combinations of the two dysfunctional variants are major causes of gout,
      thereby providing a new approach for prevention and treatment of the gout high
      risk population.

PMID- 22132967
TI  - The PRPP synthetase spectrum: what does it demonstrate about nucleotide
      syndromes?
AB  - Defects in X-linked phosphoribosylpyrophosphate synthetase 1 (PRPS1) manifest as
      follows: (1) PRS-I enzyme "superactivity" (gain-of-function mutations affecting
      allosteric regions); (2) PRS-I overexpression (which may be linked to miRNA
      mutation); (3) severe PRS-I deficiency/Arts syndrome (missense mutations
      producing loss-of-function); (4) moderate PRS-I deficiency/Charcot-Marie-Tooth
      disease-5 (less severe loss-of-function mutations); and (5) mild PRS-I
      deficiency/Deafness-2 (mutations producing slight destabilization). Similar to
      Lesch-Nyhan disease, PRPS1-related disorders arise from phosphoribosyl
      pyrophosphate (PRPP)-dependent nucleotide "depletion" of purine nucleotides
      (e.g., ATP, GTP). S-adenosylmethionine (SAMe) appears to partially alleviate
      purine depletion via a PRPP-independent path. Synthesis of pyrimidine nucleotides
      is PRPP dependent, with uridine monophosphate synthase deficiency producing
      pyrimidine nucleotide depletion. But pyrimidine salvage from uridine does not
      require PRPP, and this nucleoside is transported freely to pyrimidine-depleted
      tissues. Regulation of nicotinamide nucleotides is less clear; synthesis from
      pyridine nucleobases is PRPP dependent. Nucleotide "depletion" contrasts with
      nucleotide "toxicity," exemplified by the purine disorders adenosine deaminase
      (ADA) and purine nucleoside phosphorylase (PNP) deficiencies or by pyrimidine
      nucleotidase deficiency. These are characterized by the accumulation of one or
      more abnormal nucleotides such as succinyl- or deoxy-nucleotides or their
      metabolites, which interrupt other nucleotide or related pathways or are toxic to
      specific cell types. Theoretically, purine toxicity disorders would not be
      ameliorated by SAMe therapy, and this was confirmed for one adenylosuccinate
      lyase-deficient child. Nucleotide defects may also be seen as an aspect of
      mitochondrial disease, with SAMe-based mitochondrial therapy perhaps meriting
      further investigation.

PMID- 22132968
TI  - Stable isotope dilution mass spectrometric assay for PRPP using enzymatic
      procedures.
AB  - 5-Phosphoribosyl-1-pyrophosphate (PRPP) is an important regulator of de novo
      purine synthesis. A method for the measurement of PRPP in erythrocytes was
      designed, which is based on the determination of [(13)C(5)]glutamate derived from
      [(13)C(5)]glutamine following the utilization of PRPP by the action of
      amidophosphoribosyltransferase. The present study describes a gas chromatographic
      mass spectrometric method for determination of [(13)C(5)]glutamate using
      [(13)C(2)]glutamate as an internal standard. The methods involved purification by
      anion-exchange chromatography using a BondElut SAX and derivatization with
      isobutyl chlorocarbonate in water-methanol-pyridine. Quantitation was performed
      by selected ion monitoring of the protonated molecular ions in the chemical
      ionization mode. The intra-day reproducibility in the amounts of
      [(13)C(5)]glutamate determined was in good agreement with the actual amounts
      added in erythrocytes. A linear relationship was found between the amount of PRPP
      added and the amount of [(13)C(5)]glutamate formed from [(13)C(5)]glutamine using
      amidophosphoribosyltransferase.

PMID- 22132969
TI  - Gene expression of enzymes required for the de novo synthesis and degradation of
      pyrimidines in rat peripheral tissues and brain.
AB  - Tissue-specific expression of the genes coding for the six enzymes of the de novo
      pyrimidine synthesis and for the first enzyme of the degradation pathway,
      dihydropyrimidine dehydrogenase (DPD), was analyzed in the rat using the in situ
      hybridization technique. Transcripts of the biosynthetic enzymes were detected in
      liver, kidney, and spleen with the highest expression in the white pulp. DPD was
      also transcribed in these organs with a striking layer-specific localization of
      DPD mRNA and protein in the kidney. All enzyme mRNAs were present in brain at low
      levels, but with region- and cell-specific differences. The relatively high
      expression in cortical regions including cerebellum and hippocampus points to a
      fundamental role of pyrimidine metabolism in brain function.

PMID- 22132970
TI  - Initial studies to define the physiologic role of cN-II.
AB  - IMP preferring cytosolic 5'-nucleotidase II (cN-II) is a widespread enzyme whose
      amino acid sequence is highly conserved among vertebrates. Fluctuations of its
      activity have been reported in some pathological conditions and its mRNA levels
      have been proposed as a prognostic factor for poor outcome in patients with adult
      acute myeloid leukemia. As a member of the oxypurine cycle, cN-II is involved in
      the regulation of intracellular concentration of 5'-inosine monophosphate (IMP),
      5'-guanosine monophosphate (GMP), and also 5-phosphoribose 1-pyrophosphate (PRPP)
      and is therefore involved in the regulation of purine and pyrimidine de novo and
      salvage synthesis. In addition, several studies demonstrated the involvement of
      cN-II in pro-drug metabolism. Notwithstanding some publications indicating that
      cN-II is essential for the survival of several cell types, its role in cell
      metabolism remains uncertain. To address this issue, we built two eucaryotic
      cellular models characterized by different cN-II expression levels: a
      constitutive cN-II knockdown in the astrocytoma cell line (ADF) by short hairpin
      RNA (shRNA) strategy and a cN-II expression in the diploid strain RS112 of
      Saccharomyces cerevisiae. Preliminary results suggest that cN-II is essential for
      cell viability, probably because it is directly involved in the regulation of
      nucleotide pools. These two experimental approaches could be very useful for the
      design of a personalized chemotherapy.

PMID- 22132971
TI  - Inosine, not adenosine, initiates endothelial glycocalyx degradation in cardiac
      ischemia and hypoxia.
AB  - Ischemia/reperfusion and hypoxia/reoxygenation of the heart both induce shedding
      of the coronary endothelial glycocalyx. The processes leading from an oxygen
      deficit to shedding are unknown. An involvement of resident perivascular cardiac
      mast cells has been proposed. We hypothesized that either adenosine or inosine or
      both, generated by nucleotide catabolism, attain the concentrations in the
      interstitial space sufficient to stimulate A3 receptors of mast cells during both
      myocardial ischemia/reperfusion and hypoxia/reoxygenation. Isolated hearts of
      guinea pigs were subjected to either normoxic perfusion (hemoglobin-free Krebs
      Henseleit buffer equilibrated with 95% oxygen), 20 minutes hypoxic perfusion
      (buffer equilibrated with 21% oxygen) followed by 20 minutes reoxygenation, or 20
      minutes stopped-flow ischemia followed by 20 minutes normoxic reperfusion (n = 7
      each). Coronary venous effluent was collected separately from so-called
      transudate, a mixture of interstitial fluid and lymphatic fluid appearing on the
      epicardial surface. Adenosine and inosine were determined in both fluid
      compartments using high-performance liquid chromatography. Damage to the
      glycocalyx was evident after ischemia/reperfusion and hypoxia/reoxygenation.
      Adenosine concentrations rose to a level of 1 MUM in coronary effluent during
      hypoxic perfusion, but remained one order of magnitude lower in the interstitial
      fluid. There was only a small rise in the level during postischemic perfusion. In
      contrast, inosine peaked at over 10 MUM in interstitial fluid during hypoxia and
      also during reperfusion, while effluent levels remained relatively unchanged at
      lower levels. We conclude that only inosine attains levels in the interstitial
      fluid of hypoxic and postischemic hearts that are sufficient to explain the
      activation of mast cells via stimulation of A3-type receptors.

PMID- 22132972
TI  - Lipophilic prodrugs and formulations of conventional (deoxy)nucleoside and
      fluoropyrimidine analogs in cancer.
AB  - Many drugs that are currently used for the treatment of cancer have limitations,
      such as induction of resistance and/or poor biological half-life, which reduce
      their clinical efficacy. To overcome these limitations, several strategies have
      been explored. Chemical modification by the attachment of lipophilic moieties to
      (deoxy)nucleoside analogs should enhance the plasma half-life, change the
      biodistribution, and improve cellular uptake of the drug. Attachment of a
      lipophilic moiety to a phosphorylated (deoxy)nucleoside analog will improve the
      activity of the drugs by circumventing the rate-limiting activation step of
      (deoxy)nucleoside analogs. Encapsulating drugs in nanoparticles or liposomes
      protects the drug against enzymatic breakdown in the plasma and makes it possible
      to get lipophilic compounds to the tumor site. In this review, we discuss the
      considerable progress that has been made in increasing the efficacy of classic
      (deoxy)nucleoside and fluoropyrimidine compounds by chemical modifications and
      alternative delivery systems.

PMID- 22132973
TI  - Fludarabine nucleoside modulates nuclear "survival and death" proteins in
      resistant chronic lymphocytic leukemia cells.
AB  - The nuclear mechanisms by which fludarabine nucleoside (F-ara-A) induces
      apoptosis have been investigated in human MEC1 cells derived from B-cell chronic
      lymphocytic leukemia. Upon treatment of cells with F-ara-A (100 MUM, 72 hours),
      15 nuclear proteins changed in abundance by more than 2-fold. Nuclear proteins up
      regulated included calmodulin (4.3-fold), prohibitin (3.9-fold), beta-actin
      variant (3.7-fold), and structure-specific recognition protein 1 (3.7-fold);
      those down-regulated included 60S ribosomal protein P2B (0.12-fold), fumarate
      hydratase (0.19-fold), splicing factor arginine/serine-rich 3 (0.35-fold), and
      replication protein A2 (0.42-fold). These changes in the levels of specific
      proteins promote survival or apoptosis; because the end result is apoptosis of
      MEC1 cells, apoptotic effects predominate.

PMID- 22132974
TI  - Combination effects of digalloylresveratrol with arabinofuranosylcytosine and
      difluorodeoxycytidine in human leukemia and pancreatic cancer cells.
AB  - Digalloylresveratrol (DIG) is a newly synthesized agent aimed to combine the
      biological effects of the natural compounds, gallic acid and resveratrol, which
      both are free radical scavengers exhibiting anticancer activity. In this study,
      we investigated the effects of DIG on the growth of human HL-60 leukemia cells
      and on the colony formation of human BxPC-3 and PANC-1 pancreatic cancer cells.
      DIG was applied alone and in combination with arabinofuranosylcytosine (Ara-C) or
      difluorodeoxycytidine (dFdC), depending on the cell line employed. All IC(50)
      values observed were in the low micromolar range rendering DIG a promising
      antitumor compound in vitro. Considering the combination experiments, DIG yielded
      additive effects with Ara-C in HL-60 cells and-to a lesser extent-with dFdC in
      BxPC-3 and PANC-1 cells. Owing to our results, DIG may be further investigated in
      vitro and in animals.

PMID- 22132975
TI  - Deoxyribose protects against rapamycin-induced cytotoxicity in colorectal cancer
      cells in vitro.
AB  - Thymidine phosphorylase (TPase) is also known as the platelet-derived endothelial
      cell growth factor (PD-ECGF) and plays a role in angiogenesis. Deoxyribose (dR; a
      downstream TPase-product) addition to endothelial cells may stimulate FAK and
      p70/S6k signaling, which can be inhibited by rapamycin. Rapamycin is a specific
      mammalian target of the rapamycin (mTOR) inhibitor, a kinase that lies directly
      upstream of p70/S6k. This suggests a role for TPase in the mTOR/p70/S6k pathway.
      In order to study this in more detail, we exposed cells with and without TPase
      expression to dR and rapamycin and determined the effect on cell growth. We
      observed protection in cytotoxicity in Colo320 cells, but not Colo320 TP1 cells.
      This was in part mediated by activation of p70/S6k and inhibition of autophagy.
      Further studies are recommended to elucidate the mechanism behind the protective
      effect of dR.

PMID- 22132976
TI  - Determination of the phosphorylated metabolites of gemcitabine and of
      difluorodeoxyuridine by LCMSMS.
AB  - Gemcitabine is an established chemotherapy agent in several solid tumors. Its
      mechanism of action has been theoretically established and this is supported with
      strong experimental evidence. However, certain aspects of the resistance
      mechanism for this agent remain elusive. We present a method of analysis using
      tandem liquid chromatography and mass spectrometry that provides a broader, yet
      more focused view of the action of gemcitabine and its primary metabolite,
      difluorodeoxyuridine in relation to the (deoxy) nucleoside and (deoxy) nucleotide
      pools in tumor cell lines.   Alcoholic cytosole extracts were incubated with
      alkaline phosphatase reducing the nucleotide pools to their respective
      nucleosides. Determination of the nucleoside content by a sensitive LCMSMS method
      before and after incubation enables the calculation of the total amount of
      phosphorylation of each (deoxy) nucleoside in the cell. Incubation with
      clinically relevant levels of gemcitabine (dFdC) or difluorodeoxyuridine (dFdU)
      for 24 hours enabled the determination of the changes in the (deoxy) nucleotide
      pools in relation to chemotherapeutic and toxicological effects. Confirmation of
      the presence of dFdC phosphorylation is presented as well as direct evidence of
      dFdU phosphorylation after both dFdC and dFdU treatment. Differences in the
      nucleotide pools are presented after dFdC and dFdU incubation, indicating that
      dFdU might have more chemotherapeutic properties than previously believed.

PMID- 22132977
TI  - Regulation of deoxycytidine kinase expression and sensitivity to gemcitabine by
      micro-RNA 330 and promoter methylation in cancer cells.
AB  - Deoxycytidine kinase (dCK) is essential for phosphorylation of natural
      deoxynucleosides and analogs, such as gemcitabine and cytarabine, two widely used
      anticancer compounds. Regulation of dCK is complex, including Ser-74
      phosphorylation. We hypothesized that dCK could be regulated by two additional
      mechanisms: micro-RNA (miRNA) and promoter methylation. Methylation-specific PCR
      (MSP) revealed methylation of the 3' GC box in three out of six cancer cell
      lines. The 3' GC box is located at the dCK promoter region. The methylation
      status was related to dCK mRNA expression. TargetScan and miRanda prediction
      algorithms revealed several possible miRNAs targeting dCK and identified miR-330
      (micro-RNA 330) as the one conserved between the human, the chimpanzee, and the
      rhesus monkey genomes. Expression of miR-330 in various colon and lung cancer
      cell lines, as measured by QRT-PCR, varied five-fold between samples and
      correlated with in-vitro gemcitabine resistance (R = 0.82, p = 0.04). Exposure to
      gemcitabine also appeared to influence miR-330 levels in these cell lines.
      Furthermore, in our cell line panel, miR-330 expression negatively correlated
      with dCK mRNA expression (R = 0.74), suggesting a role of miR-330 in post
      transcriptional regulation of dCK. In conclusion, the 3' GC box and miR-330 may
      regulate dCK expression in cancer cells.

PMID- 22132978
TI  - Characterization of oligomeric and kinetic properties of tomato thymidine kinase
      1.
AB  - The gene encoding thymidine kinase 1 from tomato (toTK1) has in combination with
      azidothymidine (AZT) recently been proposed as a powerful suicide gene for
      anticancer gene therapy. The toTK1/AZT combination has been demonstrated to have
      several advantages for the treatment of glioblastomas because AZT can easily
      penetrate the blood-brain barrier and toTK1 can efficiently phosphorylate AZT and
      also AZT-monophosphate. In a pursuit to further understand the properties of
      toTK1, we examined the oligomerization properties of recombinant toTK1 and its
      effect on enzyme kinetics. Previously, it has been shown that human TK1 is a
      dimer in the absence of ATP and a tetramer if preincubated with ATP. However, we
      show here that ATP preincubation did not result in a structural shift from dimer
      to tetramer in toTK1. For human TK1 pretreated with ATP, the K(m) value decreased
      20-fold, but toTK1's K(m) value did not show a dependence on the presence or
      absence of ATP. Furthermore, toTK1 was always found in a highly active form.

PMID- 22132979
TI  - A new expression vector for production of enzymes in the yeast Saccharomyces
      (Lachancea) kluyveri.
AB  - We overexpressed and purified enzymes involved in the pyrimidine catabolic
      pathway in the yeast Saccharomyces (Lachancea) kluyveri. A new vector was
      therefore designed, providing the first specific expression system in
      Saccharomyces kluyveri. The URC1 gene was overexpressed and a soluble protein
      obtained and successfully purified using the C-terminally added His-tag. Our
      system will be used for further studies of the structure and function of the
      enzymes belonging to the URC pyrimidine degradation pathway.

PMID- 22132980
TI  - Inborn errors of purine and pyrimidine metabolism: how much we owe to H. Anne
      Simmonds.
AB  - Purines and pyrimidines, regarded for a long time merely as building blocks for
      nucleic acid synthesis and intermediates in the transfer of metabolic energy,
      have attracted increasing attention after genetically determined aberrations in
      their metabolism were linked to a range of symptoms from hyperuricemia and
      immunodeficiency to neurological disorders. The pathogenesis of such disorders
      involves cell or mitochondrial damage, but the molecular mechanisms underlying
      symptoms is often unclear. H. Anne Simmonds made major contributions to the
      metabolic, clinical, and molecular aspects of these disorders and the Purine
      Research Laboratory, which she established in London, became the world center for
      clinical and experimental studies in the field. We owe her gratitude not only for
      this direct contribution but also for her enthusiasm for purine and pyrimidine
      research that she transmitted to generations of scientists. Our research in this
      field stemmed from expertise in pyridine metabolism and its connection with
      purines, and from clinical involvement with biochemical diagnosis of enzyme
      deficiencies. We joined H. Anne Simmonds in studying the biochemical basis of
      altered NAD content in erythrocytes of PNP- and HPRT-deficient patients,
      discovering some alterations in NAD synthesis and breakdown.

PMID- 22132981
TI  - Purine nucleoside phosphorylase deficiency: a mutation update.
AB  - Purine nucleoside phosphorylase (PNPase) deficiency is an autosomal recessive
      disorder affecting purine degradation and salvage pathways. Clinically, patients
      typically present with severe immunodeficiency, neurological dysfunction, and
      autoimmunity. Biochemically, PNPase deficiency may be suspected in the presence
      of hypouricemia. We report biochemical and genetic data on a cohort of seven
      patients from six families identified as PNPase deficient. In all patients,
      inosine, deoxyinosine, guanosine, and deoxyguanosine were elevated in urine, and
      mutation analysis revealed seven different mutations of which three were novel.
      The mutation c.770A>G resulted in the substitution p.His257Arg. A second novel
      mutation c.257A>G (p.His86Arg) was identified in two siblings and a third novel
      mutation, c.199C>T (p.Arg67X), was found in a 2-year-old female with delayed
      motor milestones and recurrent respiratory infections. A review of the literature
      identified 67 cases of PNPase deficiency from 49 families, including the cases
      from our own laboratory. PNPase deficiency was confirmed in 30 patients by
      genotyping and 24 disease causing mutations, including the three novel mutations
      described in this paper, have been reported to date. In five of the seven
      patients, plasma uric acid was found to be within the pediatric normal range,
      suggesting that PNPase deficiency should not be ruled out in the absence of
      hypouricemia.

PMID- 22132982
TI  - Hypoxanthine guanine phosphoribosyltransferase (HPRT) mutations in the Asian
      population.
AB  - Mutation of hypoxanthine guanine phosphoribosyltransferase (HPRT) gives rise to
      Lesch-Nyhan syndrome, which is characterized by hyperuricemia, severe motor
      disability, and self-injurious behavior, or HPRT-related gout (Kelley-Seegmiller
      syndrome). The marked heterogeneity of HPRT deficiency is well known, with more
      than 300 mutations at the HPRT gene locus having been reported (deletions,
      insertions, duplications, abnormal splicing, and point mutations at different
      sites of the coding region from exons 1 to 9). We have identified mutations in
      Asian families with patients manifesting different clinical phenotypes, including
      rare cases of female subjects, by analyzing all nine exons of the HPRT gene
      (HPRT1) from genomic DNA and reverse-transcribed mRNA using the polymerase chain
      reaction technique coupled with direct sequencing. We developed suitable methods
      to detect the mutations identified from respective families with HPRT deficiency.
      Then, prenatal genetic diagnoses in HPRT-deficient families were carried out
      using both mRNA and genomic DNA from chorionic villi or amniotic fluid cells. As
      shown here in the heterogeneity of HPRT mutations, the spectrum of 70 mutations
      identified in the Asian population fits the four main conclusions that emerged
      previously from worldwide analysis.

PMID- 22132983
TI  - Simultaneous determination of purine and pyrimidine metabolites in HPRT-deficient
      cell lines.
AB  - Genetic mutations in the purine salvage enzyme, hypoxanthine-guanine
      phosphoribosyltransferase (HPRT), are known to cause Lesch-Nyhan syndrome and
      Kelley-Seegmiller syndrome. In patients, purine metabolism is different from that
      of normal persons. We have previously developed a method for simultaneously
      determining the concentration of purine and pyrimidine nucleosides and
      nucleotides. This system was applied to determine the concentrations of
      nucleosides and nucleotides in HPRT-deficient cell lines. The amount of inosine
      5'-monophosphate (IMP) was different in Lesch-Nyhan syndrome, Kelley-Seegmiller
      syndrome, and control cell lines. The difference in the amount of IMP confirmed
      the mutation of the enzyme.

PMID- 22132984
TI  - HPRT deficiency: identification of twenty-four novel variants including an
      unusual deep intronic mutation.
AB  - Hypoxanthine phosphoribosyltranferase (HPRT) deficiency is an X-linked disorder
      of purine salvage that ranges phenotypically from hyperuricaemia to Lesch-Nyhan
      Syndrome. Molecular testing is necessary to identify female carriers within
      families as a prelude to prenatal diagnosis. During the period 1999-2010 the
      Purine Research Laboratory studied 106 patients from 68 different families.
      Genomic sequencing revealed mutations in 88% of these families, 24 of which were
      novel. In eight patients, exon sequencing was not informative. Copy-DNA analysis
      in one patient revealed an insertion derived from a deep intronic sequence with a
      genomic mutation flanking this region, resulting in the creation of a false exon.
      Carrier testing was performed in 21 mothers of affected patients, out of these,
      81% (17) were found to be carriers of the disease-associated mutation. Our
      results confirm the extraordinary variety and complexity of mutations in HPRT
      deficiency. A combination of genomic and cDNA sequencing may be necessary to
      define mutations.

PMID- 22132985
TI  - Molecular characterization of a deletion in the HPRT1 gene in a patient with
      Lesch-Nyhan syndrome.
AB  - Lesch-Nyhan syndrome is caused by a deficiency of hypoxanthine
      phosphoribosyltransferase (HPRT) encoded by HPRT1. About 20% of patients have a
      deletion of HPRT1 and large deletions of HPRT1 are not always fully characterized
      at the molecular level. Here, we report on a case of Lesch-Nyhan syndrome with a
      33-kb deletion involving exon 1 of HPRT1. This novel mutation is caused by a
      nonhomologous recombination between different classes of interspersed repetitive
      DNA.

PMID- 22132986
TI  - Molecular analysis of X-linked inborn errors of purine metabolism: HPRT1 and
      PRPS1 mutations.
AB  - Mutations of two enzyme genes, HPRT1 encoding hypoxanthine guanine
      phosphoribosyltransferase (HPRT) and PRPS1 encoding a catalytic subunit (PRS-I)
      of phosphoribosylpyrophosphate synthetase, cause X-linked inborn errors of purine
      metabolism. Analyzing these two genes, we have identified three HPRT1 mutations
      in Lesch-Nyhan families following our last report. One of them, a new mutation
      involving the deletion of 4224 bp from intron 4 to intron 5 and the insertion of
      an unknown 28 bp, has been identified. This mutation resulted in an enzyme
      polypeptide with six amino acids deleted due to abnormal mRNA skipping exon 5.
      The other HPRT1 mutations, a single base deletion (548delT, 183fs189X), and a
      point mutation causing a splicing error (532+1G>A, 163fs165X) were detected first
      in Japanese patients but have been reported in European families. On the other
      hand, in the analysis of PRPS1, no mutation was identified in any patient.

PMID- 22132987
TI  - Inborn errors in purine metabolism: role of 5'-nucleotidases and their
      involvement in the etiology of neurological impairments.
AB  - A number of scientists have been involved for decades in the study of nucleotide
      metabolism in different species of living beings. We are, therefore, aware of the
      relevant roles of purine compounds and of the many different ways in which these
      compounds influence cell life, acting both inside and outside the cells.
      Nevertheless, the consequences of an alteration (lack of expression, or hypo- or
      hyperexpression) in the activity of enzymes involved in the metabolism of these
      compounds are sometimes surprising, and far from being mechanistically explained.
      Alterations in enzyme activities involved in nucleotide metabolism are frequently
      associated with syndromes characterized by two different types of problems--one,
      metabolic, which is expected and can be easily explained, and the second,
      neurological and behavioral. Neurological and behavioral impairments are more
      difficult to explain and show a very high degree of individual variability. The
      molecular bases of the neurological impairment linked to purine metabolism
      disorders have been extensively studied. These studies have generated a lot of
      hypotheses but very few certainties. In this short review, neurological and
      behavioral symptoms linked to the dysfunction of some enzymes involved in purine
      synthesis, catabolism, and salvage will be briefly described, with particular
      attention to their metabolic and regulatory consequences. Finally, attention will
      be focused on the 5'-nucleotidase family members and on their involvement in the
      regulation of purine and pyrimidine metabolism.

PMID- 22132988
TI  - Detection of mutant uromodulin in transgenic mouse harboring a mutant human UMOD
      gene.
AB  - Uromodulin is the most abundant protein secreted in urine, and the mutated form
      of the uromodulin gene is associated with uromodulin-associated kidney disease
      (UAKD). Although uromodulin accumulates in the kidney of UAKD patients, it is
      unclear whether this is the wildtype or mutant form. In this study, we
      established a liquid chromatography (LC)-mass spectrometry/mass spectrometry
      (MS/MS)-based method for the detection of uromodulin mutants, using the C148W
      mutant as a target molecule. Membrane and cytosolic fractions of kidney samples
      from transgenic (Tg) mice expressing the C148W uromodulin mutant were shown to
      contain human uromodulin by western blotting, and mutant uromodulin with the
      C148W mutant sequence was observed by proteomic and selected reaction monitoring
      analyses. Our LC-MS/MS-based method is therefore useful for detection of mutant
      uromodulin that is undetectable by western blotting alone.

PMID- 22132989
TI  - The increased protein level of URAT1 was observed in obesity/metabolic syndrome
      model mice.
AB  - To elucidate the mechanism of obesity/metabolic syndrome-related hyperuricemia,
      this study aimed to determine the expression levels of transport systems for
      urate absorption (Urat1, Smct1, Glut9) and urate secretion (Abcg2). The kidneys
      of two obesity models in mice were used: 1) leptin-deficient mice (ob/ob mice)
      and 2) Quick fat diet model.   1) 8-week-old male ob/ob mice demonstrated the
      increased protein levels of Slc22a12 (Urat1), Slc2a9 (Glut9), and Abcg2 (Abcg2)
      and a decreased protein level of Slc5a8 (Smct1). However, no significant changes
      in the mRNA levels of these genes were observed.   2) C57BL/6 mice were fed with
      a Quick fat diet (crude fat content: 13.6%) from the age of 24 to 28 weeks (Quick
      fat diet group). The average body weights of the Quick fat diet group were
      heavier than those of the control group fed with a normal diet (crude fat
      content: 4.8%). The mRNA levels of Slc22a12, Slc2a9, Abcg2, or Slc5a8 did not
      change significantly in both groups. The protein levels of Slc22a12 (Urat1) and
      Abcg2 (Abcg2) increased significantly in the Quick fat diet group. Those of
      Slc2a9 (Glut9) and Slc5a8 (Smct1) were not changed significantly in the Quick fat
      diet group.   In conclusion, the Quick fat diet enhanced the protein levels of
      Urat1 and Abcg2 without any changes in their mRNA transcription levels. The cause
      of obesity/metabolic syndrome-associated hyperuricemia appears to be associated
      with the urate reabsorption transporter Urat1 protein enhanced by fat.

PMID- 22132990
TI  - Increased expression of SLC2A9 decreases urate excretion from the kidney.
AB  - Urate is the final metabolite of purine in humans. Renal urate handling is
      clinically important because under-reabsorption or underexcretion causes
      hypouricemia or hyperuricemia, respectively. We have identified a urate-anion
      exchanger, URAT1, localized at the apical side and a voltage-driven urate efflux
      transporter, URATv1, expressed at the basolateral side of the renal proximal
      tubules. URAT1 and URATv1 are vital to renal urate reabsorption because the
      experimental data have illustrated that functional loss of these transporter
      proteins affords hypouricemia. While mutations affording enhanced function via
      these transporter proteins on urate handling is unknown, we have constructed
      kidney-specific transgenic (Tg) mice for URAT1 or URATv1 to investigate this
      problem. In our study, each transgene was under the control of the mouse URAT1
      promoter so that transgene expression was directed to the kidney. Plasma urate
      concentrations in URAT1 and URATv1 Tg mice were not significantly different from
      that in wild-type (WT) mice. Urate excretion in URAT1 Tg mice was similar to that
      in WT mice, while URATv1 Tg mice excreted more urate compared with WT. Our
      results suggest that hyperfunctioning URATv1 in the kidney can lead to increased
      urate reabsorption and may contribute to the development of hyperuricemia.

PMID- 22132991
TI  - Apical voltage-driven urate efflux transporter NPT4 in renal proximal tubule.
AB  - Uric acid (urate) is the end product of purine metabolism in humans. Human
      kidneys reabsorb a large proportion of filtered urate. This extensive renal
      reabsorption, together with the fact that humans do not possess uricase that
      catalyzes the biotransformation of urate into allantoin, results in a higher
      plasma urate concentration in humans compared to other mammals. A major
      determinant of plasma urate concentration is renal excretion as a function of the
      balance between reabsorption and secretion. We previously identified that renal
      urate absorption in proximal tubular epithelial cells occurs mainly via apical
      urate/anion exchanger, URAT1/SLC22A12, and by facilitated diffusion along the
      trans-membrane potential gradient by the basolateral voltage-driven urate efflux
      transporter, URATv1/SLC2A9/GLUT9. In contrast, the molecular mechanism by which
      renal urate secretion occurs remains elusive. Recently, we reported a newly
      characterized human voltage-driven drug efflux transporter, hNPT4/SLC17A3, which
      functions as a urate exit pathway located at the apical side of renal proximal
      tubules. This transporter protein has been hypothesized to play an important role
      with regard to net urate efflux. An in vivo role of hNPT4 is supported by the
      fact that missense mutations in SLC17A3 present in hyperuricemia patients with
      urate underexcretion abolished urate efflux capacity in vitro. Herein, we report
      data demonstrating that loop diuretics and thiazide diuretics substantially
      interact with hNPT4. These data provide molecular evidence for loop and thiazide
      diuretics-induced hyperuricemia. Thus, we propose that hNPT4 is an important
      transepithelial proximal tubular transporter that transports diuretic drugs and
      operates functionally with basolateral organic anion transporters 1/3
      (OAT1/OAT3).

PMID- 22132993
TI  - Translocation of nucleoside analogs across the plasma membrane in hematologic
      malignancies.
AB  - Nucleoside analogs are currently used in the treatment of various hematologic
      malignancies due to their ability to induce apoptosis of lymphoid cells. For
      nucleoside-derived drugs to exert their action, they must enter cells via
      nucleoside transporters from two gene families, SLC28 and SLC29 (CNT and ENT,
      respectively). Once inside the cell, these drugs must be phosphorylated to their
      active forms. In contrast, some members of the ATP-binding cassette (ABC) protein
      family have been identified as responsible for the efflux of the phosphorylated
      forms of these nucleoside-derived drugs. Here, we review the main nucleoside
      analogs used in hematologic malignancies and focus especially on those that are
      currently used in chronic lymphocytic leukemia (CLL). Moreover, we discuss the
      pharmacological profile of the nucleoside transporters, which determines the
      bioavailability of and cell sensitivity to these nucleoside-derived drugs. We
      also discuss the expression of nucleoside transporters and their activities in
      CLL as well as the possibility of modulating these transporter activities as a
      means of modulating intracellular drug availability and, consequently,
      responsiveness to therapy.

PMID- 22132992
TI  - Human uric acid transporter 1 (hURAT1): an inhibitor structure-activity
      relationship (SAR) study.
AB  - The current study describes the chemical synthesis of a series of (2
      ethylbenzofuran-3-yl)(substituted-phenyl)methanone compounds and their subsequent
      in vitro testing via oocytes expressing hURAT1. The experimental data support the
      notion that a potent hURAT1 inhibitor requires an anion (i.e., a formal negative
      charge) to interact with the positively charged hURAT1 binding pocket. An anion
      appears to be a primary requirement in order to be a hURAT1 substrate (i.e.,
      urate) or inhibitor. We discuss the inhibitor structure-activity relationship and
      how electronically donating or withdrawing groups attached to the B-ring can
      decrease or increase inhibitory potency, respectively.

PMID- 22132995
TI  - Escherichia coli O157:H7 facilitates the penetration of Staphylococcus aureus
      into table eggs.
AB  - Fresh eggshells collected from a local farm were subjected to different levels of
      surface contamination with feces containing different levels (3 to 5 log10) of
      Escherichia coli O157:H7 or Staphylococcus aureus and incubated at 3 different
      temperatures (10, 25, and 32  degrees C). The penetration rates of contaminating
      bacteria were followed throughout the incubation period by tracing bacterial
      presence in shell, shell membranes, albumen, and yolk. The study revealed the
      ability of both E. coli O157:H7 and enterotoxigenic S. aureus to grow on shell in
      feces, penetrate the shell, and move and multiply within egg contents at
      different rates and periods depending on bacterial type and incubation
      conditions. High temperatures (25 and 32  degrees C) increased penetration rate,
      whereas storage at 10  degrees C decreased significantly the rate of penetration.
      High levels of contamination with E. coli O157:H7 also shortened the time needed
      for the penetration process. Results showed that when eggshells were contaminated
      with both organisms simultaneously, the penetration of E. coli O157:H7 preceded
      that of S. aureus and facilitated the invasion of the latter bacteria.

PMID- 22132996
TI  - Effects of zero-length and non-zero-length cross-linking reagents on the optical
      spectral properties and structures of collagen hydrogels.
AB  - We compared the effects of zero-length cross-linkers 1-ethyl-3
      (3dimethylaminopropyl) carbodiimide (EDC) and non-zero-length cross-linkers
      glycolaldehyde and glyceraldehyde on the optical and structural properties of
      three-dimensional (3D) collagen hydrogels. We evaluated these effects by
      multiphoton microscopy (MPM) that combined two-photon fluorescence (TPF) and
      second harmonic generation (SHG) contrasts and transmission electron microscopy
      (TEM). The collagen hydrogels were incubated separately with the above-mentioned
      reagents present at the concentration of 0.1 M. The incubation with
      glycolaldehyde and glyceraldehyde induced strong autofluorescence within the
      gels. We followed the formation of fluorescence with TPF signals in situ and in
      real time as well as characterized the micro- and nanostructures within cross
      linked hydrogels by examining SHG and TEM images respectively. As detected in the
      SHG images, glycolaldehyde- and glyceraldehyde-modified 5-10 MUm "fiberlike"
      collagen structures to longer, 20 MUm and more, aggregated strands while EDC had
      minimal effect on the microstructure. TEM revealed that glycolaldehyde and
      glyceraldehyde either completely eliminated collagen's characteristic native
      fibrillar striations or generated uncharacteristic fibrils with extensions. EDC
      preserved the native striation patterns, decreased the fibril diameters and
      effectively homogenized the fibrils within hydrogels assembled at 1.8-4.68 g/L
      collagen concentrations and 37  degrees C. Our findings provide a clear
      understanding on how different cross-linking reagents have very different effects
      on the collagen hydrogels. This understanding is critical for advancing tissue
      engineering and wound healing applications.

PMID- 22132997
TI  - Anticoagulation in large-volume leukapheresis: comparison between citrate- versus
      heparin-based anticoagulation on safety and CD34 (+) cell collection efficiency.
AB  - BACKGROUND AIMS: Little is known of the effect of anticoagulation on peripheral
      blood progenitor cell (PBPC) harvest during large-volume leukapheresis (LVL).
      Because of the interaction of heparin with stromal cell-derived factor (SDF)
      1alpha, it has been proposed that a heparin-based anticoagulation may result in
      an increased PBPC collection efficiency compared with standard citrate-based
      anticoagulation. METHODS: We conducted a prospective randomized trial to address
      the effect of both anticoagulation regimes on safety, subjective comfort and CD34
      (+) collection efficiency in 90 adult patients undergoing standardized LVL.
      Anticoagulation consisted of either citrate (group C) or a combination of heparin
      and low-dose citrate (group H). RESULTS: The overall incidence of adverse
      reactions (AR) during LVL was 17%. AR consisted only of citrate-related AR; no
      bleeding complications were observed. Determination of parameters of the acid
      base balance revealed a higher frequency of metabolic alkalosis in group C.
      Analysis of serum SDF-1alpha revealed no differences in SDF-1alpha plasma levels.
      There were no differences in the CD34 (+) cell collection efficiency, resulting
      in the harvest of equal CD34 (+) cell yields independent of the anticoagulation
      used. CONCLUSIONS: Our data show no clinical relevant effect of a heparin
      containing anticoagulation in terms of an increased overall CD34 (+) cell
      collection during LVL, although this regime shows some benefits in terms of the
      incidence and subjective tolerance towards AR. Based on our results the decision
      between a citrate- and heparin-substituted anticoagulation for LVL should be
      driven by patient-related factors, and should concern potential contraindications
      of both methods.

PMID- 22132998
TI  - Influence of particle size on the binding activity of proteins adsorbed onto gold
      nanoparticles.
AB  - We used optical extinction spectroscopy to study the structure of proteins
      adsorbed onto gold nanoparticles of sizes 5-60 nm and their resulting biological
      binding activity. For these studies, proteins differing in size and shape, with
      well-characterized and specific interactions-rabbit immunoglobulin G (IgG), goat
      anti-rabbit IgG (anti-IgG), Staphylococcal protein A, streptavidin, and biotin
      were used as model systems. Protein interaction with gold nanoparticles was
      probed by optical extinction measurements of localized surface plasmon resonance
      (LSPR) of the gold nanoparticles. Binding of the ligands in solution to protein
      molecules already immobilized on the surface of gold causes a small but
      detectable shift in the LSPR peak of the gold nanoparticles. This shift can be
      used to probe the binding activity of the adsorbed protein. Within the context of
      Mie theory calculations, the thickness of the adsorbed protein layer as well as
      its apparent refractive index is shown to depend on the size of the gold
      nanoparticle. The results suggest that proteins can adopt different orientations
      that depend on the size of the gold nanospheres. These different orientations, in
      turn, can result in different levels of biological activity. For example, we find
      that IgG adsorbed on spheres with diameter >=20 nm does not bind to protein A.
      This study illustrates the principle that the size of nanoparticles can strongly
      influence the binding activity of adsorbed proteins. In addition to the
      importance of this in cases of direct exposure of proteins to nanoparticles, the
      results have implications for proteins adsorbed to materials with nanometer scale
      surface roughness.

PMID- 22133003
TI  - Type 1 diabetes and measles, mumps and rubella childhood infections within the
      Italian Insulin-dependent Diabetes Registry.
AB  - AIMS: Several studies confirmed the growing rate of Type 1 diabetes mellitus in
      childhood coinciding with increasing diagnosis of viral infections. A study
      investigating the incidence of Type 1 diabetes during 1996-1997 showed a higher
      notification of viral infections in the Pavia District. The aim was to confirm
      these results. METHODS: This study evaluated the relationship between new cases
      of Type 1 diabetes and those of measles, mumps and rubella in 1996-2001,
      analysing data of newly-diagnosed Type 1 diabetes children, aged 0-14 years and
      enrolled into the RIDI (Italian Insulin-dependent Diabetes Registry) during the
      same years. Measles, rubella and mumps rates were calculated using as denominator
      the estimated 'population at risk', represented by the number of 0- to 14 year
      old subjects who did not undergo the MMR (measles, mumps and rubella)
      vaccination. In order to investigate the association between Type 1 diabetes
      incidence and measles, rubella and mumps respectively, Spearman's rank
      correlation was used. RESULTS: The analysis of the whole Registries data did not
      at first show any statistical significance between age-standardized Type 1
      diabetes incidence density and estimated rates of measles, mumps and rubella
      notifications. Excluding data from Sardinia Registry, a significant association
      was observed between Type 1 diabetes incidence and mumps (P = 0.034) and rubella
      (P = 0.014), respectively, while there was no statistical significance between
      the incidence of measles cases and diabetes rates (P = 0.269). CONCLUSIONS:
      According to our findings, mumps and rubella viral infections are associated with
      the onset of Type 1 diabetes. The statistical significance observed after
      exclusion of the Sardinian data suggests that other environmental factors may
      operate over populations with different genetic susceptibility.

PMID- 22133004
TI  - Temporal activation of beta-catenin signaling in the chondrogenic process of
      mesenchymal stem cells affects the phenotype of the cartilage generated.
AB  - Adult mesenchymal stem cells (MSCs) are an attractive cell source for cartilage
      tissue engineering. In vitro predifferentiation of MSCs has been explored as a
      means to enhance MSC-based articular cartilage repair. However, there remain
      challenges to control and prevent the premature progression of MSC-derived
      chondrocytes to the hypertrophy. This study investigated the temporal effect of
      transforming growth factor (TGF)-beta and beta-catenin signaling co-activation
      during MSC chondrogenic differentiation and evaluated the influence of these
      predifferentiation conditions to subsequent phenotypic development of the
      cartilage. MSCs were differentiated in chondrogenic medium that contained either
      TGFbeta alone, TGFbeta with transient beta-catenin coactivation, or TGFbeta with
      continuous beta-catenin coactivation. After in vitro differentiation, the pellets
      were transplanted into SCID mice. Both coactivation protocols resulted in the
      enhancement of chondrogenic differentiation of MSCs. Compared with TGFbeta
      activation, transient coactivation of TGFbeta-induction with beta-catenin
      activation resulted in heightened hypertrophy and formed highly ossified tissues
      with marrow-like hematopoietic tissue in vivo. The continuous coactivation of the
      2 signaling pathways, however, resulted in inhibition of progression to
      hypertrophy, marked by the suppression of type X collagen, Runx2, and alkaline
      phosphatase expression, and did not result in ossified tissue in vivo.
      Chondrocytes of the continuous co-activation samples secreted significantly more
      parathyroid hormone-related protein (PTHrP) and expressed cyclin D1. Our results
      suggest that temporal co-activation of the TGFbeta signaling pathway with beta
      catenin can yield cartilage of different phenotype, represents a potential MSC
      predifferentiation protocol before clinical implantation, and has potential
      applications for the engineering of cartilage tissue.

PMID- 22133005
TI  - Improved fumigation process for stored foodstuffs by using phosphine in sealed
      chambers.
AB  - In this paper we present an innovative device designed and constructed to improve
      the fumigation process for stored foodstuffs with the use of phosphine gas in
      sealed chambers. The device allowed a considerable reduction in phosphine
      production time (from about 5 to 7 days for traditional systems to 2 days for the
      equipment considered), maintaining the system below the inflammability threshold,
      and at the same time achieving the total exhaustion of aluminum (or magnesium)
      phosphide so as to avoid toxic residues at the end of the process. With the
      standard device currently available on the market, after the normal 5-7 day
      fumigating period, the powder residue contains as much as 1-2% (w/w) of
      phosphide. Thus the residues, according to current legislation, have to be
      considered toxic and harmful. To overcome this disadvantage, appropriate
      modifications were made to the cylindrical tray used for the fumigation process:
      a nebulizer was installed, which has the function of increasing the moisture of
      the air spreading around the phosphide pellets and allowing a more rapid reaction
      with phosphide. Moreover, the cylindrical tray was also heated by means of an
      electrical resistance, and temperature was checked by a thermostat, so as to
      always obtain the same efficiency, independently of outside temperature, for both
      hot and cold periods, since reaction speed depends on the system temperature
      considered. In addition, a control device for air saturation allows condensation
      processes to be avoided. Using the modified cylindrical tray we performed tests
      to determine the best values of humidity and temperature for the process
      concerned, avoiding phosphine concentrations that might result in a fire hazard,
      and the remixing of phosphide pellets inside the cylindrical tray. Our
      experimental data allowed us to obtain a mathematical model used to gain an
      insight into the process in question.

PMID- 22133006
TI  - Evaluation of temperature effect on the interaction between beta-lactoglobulin
      and anti-beta-lactoglobulin antibody by atomic force microscopy.
AB  - Molecular recognition such as antigen-antibody interaction is characterized by
      the parameters of kinetics and the energy landscape. Examinations of molecules
      involved in the interaction at different temperatures using atomic force
      microscopy (AFM) can provide information on not only the effects of temperature
      on the unbinding force between a molecule of interest and a complementary
      molecule but also the parameters of kinetics and the energy landscape for
      dissociation of the molecular complex. We investigated the effect of temperature
      on the dissociation process of the complex of beta-lactoglobulin and anti-bovine
      beta-lactoglobulin IgG polyclonal antibody using AFM. Measurements of the
      unbinding forces between beta-lactoglobulin and the antibody were performed at
      25, 35, and 45  degrees C. The following results were obtained in our present
      study: (i) The unbinding forces decreased as temperature increased, suggesting
      that the binding force between beta-lactoglobulin and the antibody includes the
      force originating from temperature-dependent interactions (e.g., hydrogen
      bonding). (ii) At each temperature, the unbinding force exhibited two linear
      regimes in the force spectra, indicating that the dissociation process of the
      beta-lactoglobulin-antibody complex passes at least two energy barriers from the
      bound state to the dissociated state. (iii) The dissociation rates at zero force
      and the position of energy barriers increased as temperature increased. (iv) The
      heights of the two energy barriers in the reaction coordinates were 49.7 k(B)T
      and 14.5 k(B)T. (v) The values of roughness of the barriers were ca. 6.1 k(B)T
      and 3.2 k(B)T. Overall, the present study using AFM revealed more information
      about the beta-lactoglobulin-antibody interaction than studies using conventional
      bulk measurement such as surface plasmon resonance.

PMID- 22133007
TI  - CuO-promoted construction of N-2-aryl-substituted-1,2,3-triazoles via azide
      chalcone oxidative cycloaddition and post-triazole arylation.
AB  - An efficient one-pot three-component stepwise approach for the synthesis of N-2
      aryl-substituted-1,2,3-triazoles has been developed. By using this azide-chalcone
      oxidative cycloaddition and post-triazole arylation, a series of N-2-aryl
      substituted-1,2,3-triazoles are readily prepared under mild conditions in
      excellent yields and high regioselectivity. Both the catalyst and substrates are
      readily available.

PMID- 22133008
TI  - The depth-specific significance and relative abundance of anaerobic ammonium
      oxidizing bacteria in estuarine sediments (Medway Estuary, UK).
AB  - Variations in the overall and depth-specific significance of anammox were
      measured using (15) N isotope experiments in both bioirrigated and undisturbed
      sediments of the Medway Estuary, UK. This was performed over two surveys,
      alongside FISH experiments, to identify and track shifts in the relative
      abundance of anammox organisms with depth. In Survey 1 (initially screening for
      the presence of anammox), the potential for anammox (ra) decreased from 32%
      upstream to 6% downstream. In Survey 2, depth-specific values of ra varied
      between a maximum of 37% upstream and a minimum of 4% downstream. This was linked
      to a small population of anammox organisms accounting for < 1-8% of total
      bacteria with depth in Survey 1 and < 1-3% in Survey 2. The relationship between
      the relative abundance of anammox cells and the potential contribution of anammox
      to total N(2)  production did not however correlate. In Survey 2, infaunal
      disruption of the sediment substrata, and concomitant fluctuations of O(2)  over
      depth, did not appear to inhibit the potential for anammox, even at the most
      bioturbated site. Moreover, deficits detected in the retrieval of (15) N gas from
      denitrification in Survey 2 may imply potential links between dissimilatory
      nitrate reduction to ammonium and anammox in estuarine sediments.

PMID- 22133009
TI  - Interlaboratory comparison of real-time PCR protocols for quantification of
      general fecal indicator bacteria.
AB  - The application of quantitative real-time PCR (qPCR) technologies for the rapid
      identification of fecal bacteria in environmental waters is being considered for
      use as a national water quality metric in the United States. The transition from
      research tool to a standardized protocol requires information on the
      reproducibility and sources of variation associated with qPCR methodology across
      laboratories. This study examines interlaboratory variability in the measurement
      of enterococci and Bacteroidales concentrations from standardized, spiked, and
      environmental sources of DNA using the Entero1a and GenBac3 qPCR methods,
      respectively. Comparisons are based on data generated from eight different
      research facilities. Special attention was placed on the influence of the DNA
      isolation step and effect of simplex and multiplex amplification approaches on
      interlaboratory variability. Results suggest that a crude lysate is sufficient
      for DNA isolation unless environmental samples contain substances that can
      inhibit qPCR amplification. No appreciable difference was observed between
      simplex and multiplex amplification approaches. Overall, interlaboratory
      variability levels remained low (<10% coefficient of variation) regardless of
      qPCR protocol.

PMID- 22133011
TI  - A short, rigid, structurally pure carbon nanotube by stepwise chemical synthesis.
AB  - The inaccessibility of uniform-diameter, single-chirality carbon nanotubes (CNTs)
      in pure form continues to thwart efforts by scientists to use these ultrathin
      materials in innovative applications that could revolutionize nanoscale
      electronics. Stimulated by the challenge to address this long-standing problem,
      we and other organic chemists have envisioned a new production strategy involving
      the controlled elongation of small hydrocarbon templates, such as hemispherical
      nanotube end-caps, prepared by bottom-up chemical synthesis; the diameter and rim
      structure encoded in the template would dictate the diameter and chirality of the
      resulting CNT. Toward that objective, a short [5,5] CNT has now been synthesized
      by stepwise chemical methods. This C(50)H(10) geodesic polyarene has been
      isolated, purified, crystallized, and fully characterized by NMR spectroscopy, UV
      vis absorption spectroscopy, high resolution mass spectrometry, and X-ray
      crystallography.

PMID- 22133010
TI  - Microvessel density and heparanase over-expression in clear cell renal cell
      cancer: correlations and prognostic significances.
AB  - BACKGROUND: Tumor angiogenesis is important in the progression of malignancies,
      and heparanase plays an important role in sustaining the pathology of clear cell
      renal cell cancer (ccRCC). The study was carried out to investigate the
      correlations between microvessel density (MVD) and heparanase expression
      containing prognostic significances in the patients with ccRCC. METHODS:
      Specimens from 128 patients with ccRCC were investigated by immunohistochemistry
      for MVD. RT-PCR and immunohistochemistry were used to detect heparanase
      expression. Correlations between MVD, heparanase expression, and various clinico
      pathological factors were studied. The prognostic significances of MVD and
      heparanase expression were also analysed. RESULTS: We discovered a statistically
      significant prevalence of higher MVD in ccRCC compared with adjacent normal renal
      tissues. MVD was positively correlated with TNM stage and distant metastasis in
      ccRCC patients, and was also correlated with the expression level of
      heparanase.Heparanase is over-expressed and correlated with TNM stage, histologic
      grade, distant metastasis and lymphatic metastasis in ccRCC. High MVD and
      heparanase over-expression inversely correlate with the survival of ccRCC
      patients. CONCLUSIONS: Heparanase contributes to angiogenesis of ccRCC and over
      expression of heparanase is an independent predictors of prognosis for ccRCC. MVD
      is correlated with tumor development and metastasis in ccRCC.

PMID- 22133012
TI  - Endothelial dysfunction, inflammation, and oxidative stress in obese children and
      adolescents: markers and effect of lifestyle intervention.
AB  - With an increasing prevalence, pediatric obesity is often a prelude to adulthood
      obesity, and represents a major public health issue. Comorbidities are very
      common and severe in obese adults, justifying the search for earlier markers or
      risk factors for cardiovascular diseases in obese children. Endothelial
      dysfunction has been found to be present in the early stages of atherosclerosis,
      and can be non-invasively assessed with widely accepted and well-standardized
      techniques at the macrocirculation level. Endothelial dysfunction at the
      microcirculation level is less documented in obese children. Obesity in children
      has been repeatedly and independently correlated to endothelial dysfunction,
      inflammation and oxidative stress markers, although the relationship between
      these factors remains to be investigated. However, this would not only allow
      substantial improvements in risk stratification, but also provide essential data
      regarding the evolution of endothelial dysfunction in childhood obesity,
      especially during puberty when pro-inflammatory and pro-oxidative changes, with
      relative insulin resistance, occur. Therapeutic strategies such as lifestyle
      interventions in early childhood obesity appear all the more necessary, optimally
      including both exercise and diet because of their known effects on inflammatory
      and oxidative stress markers, potentially reversing endothelial dysfunction.

PMID- 22133013
TI  - Contribution to in vitro screening of Egyptian plants for schistosomicidal
      activity.
AB  - CONTEXT: This study is a continuation of our previous work in which a bioassay
      screening of 346 methanol extracts from 281 Egyptian plant species was carried
      out for in vitro schistosomicidal activity. OBJECTIVE: Another 309 methanol
      extracts from 278 plant species were subjected to the bioassay screening using
      the same technique on viable Schistosoma mansoni Sambon (Schistosomatidae) mature
      worms in specialized culture medium (Roswell Park Memorial Institute medium 1640)
      in a trial to discover a source for a schistosomiasis drug from Egyptian flora.
      MATERIAL AND METHODS: The methanol plant extracts were tested in vitro against
      viable S. mansoni mature worms in culture medium. Viability of worms was examined
      after exposure to 100 MUg/ml of the extract in the medium for 24 h. Negative
      (dimethyl sulfoxide) and positive (praziquantel) controls were simultaneously
      used. Extracts showing schistosomicidal activity were further subjected to
      determination of their (Lethal concentration) LC50 and LC90 values. RESULTS:
      Confirmed in vitro antischistosomal activity was found in 42 extracts. Of these,
      14 plant species possessed considerably high antischistosomal activity (LC50 <=
      15 ug/ml), viz. Callistemon viminalis (Soland. Ex Gaertn) Cheel, C. rigidus
      R.Br., C. speciosus (Sims.) DC, C. citrinus Stapf, Eucalyptus citriodora Hook, E.
      rostrata Dehnh., Eugenia edulis Vell, E. javanica Lam syn. Syzygium samarangense
      (Blume) Merril, Melaleuca leucadendron (L.) L., M. stypheloides Sm. (all belong
      to Myrtaceae), Cryptostegia grandiflora R.Br. (Asclepiadaceae), Zilla spinosa
      (L.) Prantl (Cruciferae), Ficus trijuja L. (Moraceae) and Fagonia mollis Delile
      (Zygophylacae). DISCUSSION AND CONCLUSION: These species may represent additional
      natural sources of bioactive material that deserve further investigation for drug
      discovery against schistosomiasis.

PMID- 22133014
TI  - Inhibition of Ostwald ripening in model beverage emulsions by addition of poorly
      water soluble triglyceride oils.
AB  - Beverage emulsions containing flavor oils that have a relatively high water
      solubility are unstable to droplet growth due to Ostwald ripening. The aim of
      this study was to improve the stability of model beverage emulsions to this kind
      of droplet growth by incorporating poorly water-soluble triglyceride oils. High
      pressure homogenization was used to prepare a series of 5 wt% oil-in-water
      emulsions stabilized by modified starch that had different lipid phase
      compositions (orange oil : corn oil). Emulsions prepared using only orange oil as
      the lipid phase were highly unstable to droplet growth during storage, which was
      attributed to Ostwald ripening resulting from the relatively high water
      solubility of orange oil. Droplet growth could be effectively inhibited by
      incorporating >= 10% corn oil into the lipid phase prior to homogenization. In
      addition, creaming was also retarded because the lipid phase density was closer
      to that of the aqueous phase density. These results illustrate a simple method of
      improving the physical stability of orange oil emulsions for utilization in the
      food, beverage, and fragrance industries.

PMID- 22133015
TI  - Dual task abilities as a possible preclinical marker of Alzheimer's disease in
      carriers of the E280A presenilin-1 mutation.
AB  - Previous dual task studies have demonstrated that patients with sporadic
      Alzheimer's disease (AD) are impaired in their ability to perform two tasks
      simultaneously compared with healthy controls, despite being able to successfully
      perform the tasks alone relatively well. Yet, it remains unclear what the
      earliest clinical manifestation of this dual task coordination deficit is. This
      study examined dual task abilities in individuals who are at risk of early-onset
      familial AD due to an E280A presenilin-1 mutation. Thirty-nine carriers of the
      gene mutation who did not meet the criteria for AD and 29 non-carrier healthy
      controls were asked to perform digit recall accompanied by a secondary tracking
      task. Individuals who were carriers of the genetic mutation demonstrated
      significantly higher dual task costs than healthy non-carriers. Dual task
      performance was found to be more sensitive to this very early stage of FAD than
      episodic memory measures. The findings support the notion that a deficit in the
      coordination mechanism of the central executive may be a pre-clinical marker for
      the early detection of AD due to the E280A presenilin-1 gene mutation.

PMID- 22133016
TI  - Environmental prevalence of Cryptococcus neoformans and Cryptococcus gattii in
      India: an update.
AB  - An overview of work done to-date in India on environmental prevalence, population
      structure, seasonal variations and antifungal susceptibility of Cryptococcus
      neoformans and Cryptococcus gattii is presented. The primary ecologic niche of
      both pathogens is decayed wood in trunk hollows of a wide spectrum of host trees,
      representing 18 species. Overall, C. neoformans showed a higher environmental
      prevalence than that of C. gattii which was not found in the avian habitats.
      Apart from their arboreal habitat, both species were demonstrated in soil and air
      in close vicinity of their tree hosts. In addition, C. neoformans showed a strong
      association with desiccated avian excreta. An overwhelming number of C.
      neoformans strains belonged to genotype AFLP1/VNI, var. grubii (serotype A),
      whereas C. gattii strains were genotype AFLP4/VGI, serotype B. All of the
      environmental strains of C. neoformans and C. gattii were mating type alpha
      (MATalpha). Contrary to the Australian experience, Eucalyptus trees were among
      the epidemiologically least important and, therefore, the hypothesis of global
      spread of C. gattii through Australian export of infected Eucalyptus seeds is
      rebutted. Reference is made to long-term colonization of an abandoned, old timber
      beam of sal wood (Shorea robusta) by a melanin positive (Mel(+)) variant of
      Cryptococcus laurentii that was pathogenic to laboratory mice.

PMID- 22133017
TI  - Toll-like receptor (TLR) 2 is upregulated on peripheral blood monocytes of
      patients with psoriatic arthritis: a role for a gram-positive inflammatory
      trigger?
AB  - Toll-like receptor (TLR) 2 and TLR4 are able to activate innate immune cells in
      response to gram-positive and gramnegative bacteria, respectively. Psoriatic
      arthritis (PsA) is a chronic inflammatory joint disease and gram-positive
      streptococcus may have a role in its pathogenesis, suggesting the importance of
      TLR2 stimulation in PsA. OBJECTIVES: To assess TLR2 and TLR4 expressions on
      innate immune cells of PsA patients, relating to clinical disease activity.
      METHODS: Forty-five patients with peripheral joint manifestations of PsA were
      included and disease activity was assessed by Disease Activity Score of 28 joint
      counts (DAS28). 32 healthy subjects constituted the control group. Membrane-bound
      TLR2 and TLR4 expressions were assessed on peripheral blood monocytes and
      neutrophils by flow cytometry. RESULTS: Twenty-seven patients had active PsA
      (DAS28 higher than 2.6) and 18 had inactive disease. TLR2 was significantly
      upregulated on monocytes in both active and inactive PsA group, comparing to
      healthy controls. TLR4 was similarly expressed in all tested groups. CONCLUSIONS:
      TLR2 is overexpressed by PsA monocytes, suggesting that gram-positive exposure
      could induce higher inflammatory responses in this disease.

PMID- 22133018
TI  - Contributions of nitric oxide synthases, dietary nitrite/nitrate, and other
      sources to the formation of NO signaling products.
AB  - Mice lacking all three nitric oxide synthase (NOS) genes remain viable even
      though deletion of the major downstream target of NO, soluble guanylyl cyclase,
      is associated with a dramatically shortened life expectancy. Moreover, findings
      of relatively normal flow responses in eNOS knockouts are generally attributed to
      compensatory mechanisms including upregulation of remaining NOS isoforms, but the
      alternative possibility that dietary nitrite/nitrate (NOx) may contribute to
      basal levels of NO signaling has never been investigated. AIM: The aim of the
      present study was to examine how NO signaling products (nitrosated and
      nitrosylated proteins) and NO metabolites (nitrite, nitrate) are affected by
      single NOS deletions and whether dietary NOx plays a compensatory role in any
      deficiency. Specifically, we sought to ascertain whether profound alterations of
      these products arise upon genetic deletion of either NOS isoform, inhibition of
      all NOS activity, NOx restriction, or all of the above. RESULTS: Our results
      indicate that while some significant changes do indeed occur, they are
      surprisingly moderate and compartmentalized to specific tissues. Unexpectedly,
      even after pharmacological inhibition of all NOSs and restriction of dietary NOx
      intake in eNOS knockout mice significant levels of NO-related products remain.
      Innovation/Conclusion: These findings suggest that a yet unidentified source of
      NO, unrelated to NOSs or dietary NOx, may be sustaining basal NO signaling in
      tissues. Given the significance of NO for redox regulation in health and disease,
      it would seem to be important to identify the nature of this additional source of
      NO products as it may offer new therapeutic avenues for correcting NO
      deficiencies.

PMID- 22133019
TI  - Graphene oxide-based supramolecular hydrogels for making nanohybrid systems with
      Au nanoparticles.
AB  - In the presence of a small amount of a proteinous amino acid
      (arginine/tryptophan/histidine) or a nucleoside (adenosine/guanosine/cytidine),
      graphene oxide (GO) forms supramolecular stable hydrogels. These hydrogels have
      been characterized by field-emission scanning electron microscopy (FE-SEM),
      atomic force microscopy (AFM), X-ray diffraction (XRD) analysis, Raman
      spectroscopy, and rheology. The morphology of the hydrogel reveals the presence
      of nanofibers and nanosheets. This suggests the supramolecular aggregation of GO
      in the presence of an amino acid/nucleoside. Rheological studies of arginine
      containing a GO-based hydrogel show a very high G' value (6.058 * 10(4) Pa),
      indicating the rigid, solid-like behavior of this gel. One of these hydrogels (GO
      tryptophan) has been successfully utilized for the in situ synthesis and
      stabilization of Au nanoparticles (Au NPs) within the hydrogel matrix without the
      presence of any other external reducing and stabilizing agents to make Au NPs
      containing the GO-based nanohybrid material. The Au NPs containing the hybrid
      hydrogel has been characterized by using UV/vis spectroscopy, X-ray diffraction
      (XRD), and transmission electron microscopy (TEM). In this study, gold salt
      (Au(3+)) has been bioreduced by the tryptophan within the hydrogel. This is a
      facile "green chemical" method of preparing the GO-based nanohybrid material
      within the hydrogel matrix. The significance of this method is the in situ
      reduction of gold salt within the gel phase, and this helps to decorate the
      nascently formed Au NPs almost homogeneously and uniformly on the surface of the
      GO nanosheets within the gel matrix.

PMID- 22133020
TI  - Risk of depression in diabetes is highest for young persons using oral anti
      diabetic agents.
AB  - AIMS: Previous studies report an increased risk of depression in patients with
      diabetes, but there is little knowledge about if or how the risk varies according
      to sex, groups of age and different type of treatments for the diabetes. We
      therefore aimed to investigate the risk of depression in different types of
      treatment for diabetes and in subgroups of age and sex. METHODS: Data on the
      Norwegian population from 20 years of age being prescribed antidepressants (n =
      253 668) and anti-diabetic agents (n = 121 392) in 2006 was obtained from the
      National Register of Prescriptions and analysed in a cross-sectional design.
      RESULTS: Individuals using insulin in monotherapy (n = 29 611) had an age- and
      sex-adjusted odds ratio of 1.47 (95% CI 1.42-1.53) for receiving antidepressants.
      Corresponding odds ratios for individuals receiving oral anti-diabetic agents in
      monotherapy (n = 76 387) and for those who received both insulin and oral anti
      diabetic agents (n = 15 394) were 1.44 (95% CI 1.41-1.47) and 1.82 (95% CI 1.80
      1.97), respectively. No major differences in risk according to age were found for
      persons receiving insulin in monotherapy, while a marked and inverse association
      between age and risk of receiving antidepressants was found for those receiving
      oral anti-diabetic agents. Highest risk of antidepressant treatment [odds ratio
      4.15 (95% CI 3.12-5.52)] was found for patients receiving both oral anti-diabetic
      agents and insulin at 30-39 years. The risk was equally increased among men and
      women. CONCLUSIONS: The risk of depression among patients with diabetes varies
      strongly according to age and type of treatment for diabetes.

PMID- 22133021
TI  - Biogeography of pelagic bacterioplankton across an antagonistic temperature
      salinity gradient in the Red Sea.
AB  - The Red Sea is a unique marine ecosystem with contrasting gradients of
      temperature and salinity along its north-to-south axis. It is an extremely
      oligotrophic environment that is characterized by perpetual year-round water
      column stratification, high annual solar irradiation, and negligible riverine and
      precipitation inputs. In this study, we investigated whether the contemporary
      environmental conditions shape community assemblages by pyrosequencing 16S rRNA
      genes of bacteria in surface water samples collected from the northeastern half
      of this water body. A combined total of 1855 operational taxonomic units (OTUs)
      were recovered from the 'small-cell' and 'large-cell' fractions. Here, a few
      major OTUs affiliated with Cyanobacteria and Proteobacteria accounted for ~93% of
      all sequences, whereas a tail of 'rare' OTUs represented most of the diversity.
      OTUs allied to Surface 1a/b SAR11 clades and Prochlorococcus related to the high
      light-adapted (HL2) ecotype were the most widespread and predominant sequence
      types. Interestingly, the frequency of taxa that are typically found in the upper
      mesopelagic zone was significantly elevated in the northern transects compared
      with those in the central, presumably as a direct effect of deep convective
      mixing in the Gulf of Aqaba and water exchange with the northern Red Sea.
      Although temperature was the best predictor of species richness across all major
      lineages, both spatial and environmental distances correlated strongly with
      phylogenetic distances. Our results suggest that the bacterial diversity of the
      Red Sea is as high as in other tropical seas and provide evidence for fundamental
      differences in the biogeography of pelagic communities between the northern and
      central regions.

PMID- 22133022
TI  - Dysidavarones A-D, new sesquiterpene quinones from the marine sponge Dysidea
      avara.
AB  - Dysidavarones A-D (1-4), four new sesquiterpene quinones possessing the
      unprecedented "dysidavarane" carbon skeleton, were isolated from the South China
      Sea sponge Dysidea avara. The structures were established by spectroscopic
      methods, and the absolute configurations were determined using quantum mechanical
      calculation of the electronic circular dichroic (ECD) spectrum and exciton
      chirality CD method. Their cytotoxic activity against four human cancer cell
      lines and PTP1B inhibitory activity were also evaluated.

PMID- 22133027
TI  - Bacterial and viral sialidases: contribution of the conserved active site
      glutamate to catalysis.
AB  - Mutagenesis of the conserved glutamic acid of influenza type A (E277) and
      Micromonospora viridifaciens (E260) sialidases was performed to probe the
      contribution of this strictly conserved residue to catalysis. Kinetic studies of
      the E260D and E260C M. viridifaciens mutant enzymes reveal that the overall
      mechanism of action has not changed. That is, the mutants are retaining
      sialidases in which glycosylation and deglycosylation are rate-limiting for
      k(cat)/K(m) and k(cat), respectively. The solvent kinetic isotope effect and
      proton inventory on k(cat) for the E260C mutant sialidase provide strong evidence
      that the newly installed cysteine residue provides little catalytic acceleration.
      The results are consistent with the conserved aspartic acid residue (D92)
      becoming the key general acid/base residue in the catalytic cycle. In addition,
      the E277D mutant influenza type A sialidase is catalytically active toward 4
      nitrophenyl alpha-D-sialoside, although no measurable hydrolysis of natural
      substrates was observed. Thus, mutating the glutamate residue (E277) to an
      aspartate increases the activation free energy of hydrolysis for natural
      substrates by >22 kJ/mol.

PMID- 22133028
TI  - Total phenolic content, antioxidant activity, and cross-cultural consumer
      rejection threshold in white and red wines functionally enhanced with catechin
      rich extracts.
AB  - White and red wines spiked with catechin-rich green tea extract and grape seed
      extract were assessed for phenolic content, antioxidant activity, and cross
      cultural consumer rejection thresholds in relation to wine as a functional food.
      Health functionality is an important factor in functional foods, and spiking pure
      compounds or plant extracts is an effective method to increase or control
      functionality. The total phenolic content and antioxidant activity were measured
      in wines spiked to different extract concentrations, namely, control and 50, 100,
      200, 400, and 800 mg/L, to confirm the dose-response curves in both white and red
      wines. Consumer rejection thresholds (CRTs) were established for spiked wines in
      a Korean and in an Australian population. Our results showed that the green tea
      extract and grape seed extract increased the antioxidant activity dose
      dependently, and the CRTs varied considerably between the Korean and the
      Australian groups, with Koreans preferring wines spiked with green tea extract
      and Australians showing a preference for wines spiked with grape seed extract.
      These results have implications for producing wine products that are enhanced in
      phenolic compounds and targeted to different cultural groups.

PMID- 22133029
TI  - Effects of shelter and enrichment on the ecology and nutrient cycling of
      microbial communities of subtidal carbonate sediments.
AB  - The interactions between physical disturbances and biogeochemical cycling are
      fundamental to ecology. The benthic microbial community controls the major
      pathway of nutrient recycling in most shallow-water ecosystems. This community is
      strongly influenced by physical forcing and nutrient inputs. Our study tests the
      hypotheses that benthic microbial communities respond to shelter and enrichment
      with (1) increased biomass, (2) change in community composition and (3) increased
      uptake of inorganic nutrients from the water column. Replicate in situ plots were
      sheltered from physical disturbance and enriched with inorganic nutrients or left
      without additional nutrients. At t(0)  and after 10 days, sediment-water fluxes
      of nutrients, O(2)  and N(2) , were measured, the community was characterized
      with biomarkers. Autochthonous benthic microalgal (BMA) biomass increased 30%
      with shelter and a natural fivefold increase in nutrient concentration; biomass
      did not increase with greater enrichment. Diatoms remained the dominant taxon of
      BMA, suggesting that the sediments were not N or Si limited. Bacteria and other
      heterotrophic organisms increased with enrichment and shelter. Daily exchanges of
      inorganic nutrients between sediments and the water column did not change in
      response to shelter or nutrient enrichment. In these sediments, physical
      disturbance, perhaps in conjunction with nutrient enrichment, was the primary
      determinant of microbial biomass.

PMID- 22133030
TI  - Importance of metabolic changes induced by chemotherapy on prognosis of early
      stage breast cancer patients: a review of potential mechanisms.
AB  - Weight variation has been reported as a side effect of chemotherapy treatment in
      early breast cancer patients and has been identified as a factor of poor
      prognosis. Causes of weight variation during chemotherapy and mechanisms involved
      in the poor prognosis have been little studied. Here is reviewed the current
      knowledge about the main causes and mechanisms involved in body weight change.
      Special emphasis is placed on factors associated with weight variation which
      could potentially be involved in the risk of relapse in breast cancer survivors.
      In recent decades, some studies have investigated the causes of weight variation
      by studying energy balance of breast cancer patients during chemotherapy. Weight
      gain or loss may be the consequence of energy imbalance through different factors
      linked with chemotherapy, such as poor treatment tolerance, decreased muscle mass
      and function, or hormonal alterations. This results in body composition
      modifications in favour of fat gain and/or lean body mass loss. Increased adipose
      tissue, especially in the abdominal region, could induce metabolic disturbances
      such as insulin resistance, through various pathways involving adipokines. These
      molecules have growth properties and could therefore play a role in cancer
      relapse. Understanding such mechanisms is key to developing preventive strategies
      for improving the prognosis of early-stage breast cancer patients.

PMID- 22133031
TI  - Colloidal stability of carbonate-coated silver nanoparticles in synthetic and
      natural freshwater.
AB  - To gain important information on fate, mobility, and bioavailability of silver
      nanoparticles (AgNP) in aquatic systems, the influence of pH, ionic strength, and
      humic substances on the stability of carbonate-coated AgNP (average diameter 29
      nm) was systematically investigated in 10 mM carbonate and 10 mM MOPS buffer, and
      in filtered natural freshwater. Changes in the physicochemical properties of AgNP
      were measured using nanoparticle tracking analysis, dynamic light scattering, and
      ultraviolet-visible spectroscopy. According to the pH-dependent carbonate
      speciation, below pH 4 the negatively charged surface of AgNP became positive and
      increased agglomeration was observed. Electrolyte concentrations above 2 mM
      Ca(2+) and 100 mM Na(+) enhanced AgNP agglomeration in the synthetic media. In
      the considered concentration range of humic substances, no relevant changes in
      the AgNP agglomeration state were measured. Agglomeration of AgNP exposed in
      filtered natural freshwater was observed to be primarily controlled by the
      electrolyte type and concentration. Moreover, agglomerated AgNP were still
      detected after 7 days of exposure. Consequently, slow sedimentation and high
      mobility of agglomerated AgNP could be expected under the considered natural
      conditions. A critical evaluation of the different methods used is presented as
      well.

PMID- 22133032
TI  - Increasing breastfeeding duration: changing the paradigm.

PMID- 22133033
TI  - Effect of packaging and storage time on survival of Listeria monocytogenes on
      kippered beef steak and turkey tenders.
AB  - The objective of our study was to determine effect of packaging method and
      storage time on reducing Listeria monocytogenes in shelf-stable meat snacks.
      Commercially available kippered beef steak strips and turkey tenders were dipped
      into a 5-strain L. monocytogenes cocktail, and dried at 23  degrees C until a
      water activity of 0.80 was achieved. Inoculated samples were packaged with 4
      treatments: (1) vacuum, (2) nitrogen flushed with oxygen scavenger, (3) heat
      sealed with oxygen scavenger, and (4) heat sealed without oxygen scavenger.
      Samples were stored at 23  degrees C and evaluated for L. monocytogenes levels at
      0, 24, 48, and 72 h. Initial levels (time 0) of L. monocytogenes were
      approximately 5.7 log CFU/cm2 for steak and tenders. After 24 h of storage time,
      a 1 log CFU/cm2 reduction of L. monocytogenes was observed for turkey tenders for
      all packaging treatments. After 48 h, turkey tenders showed >1 log CFU/cm2
      reduction of L. monocytogenes for all packaging treatments except for vacuum,
      where only 0.9 log CFU/cm2 reduction was observed. After 72 h, reductions for all
      packaging treatments for turkey tenders ranged from 1.5 to 2.4 log CFU/cm2. For
      kippered beef steak, there was no interaction between the packaging treatments
      and all storage times (P > 0.05) whereas, time was different (P <0.05). For
      kippered beef steak, there was 1 log reduction of L. monocytogenes at 24 and 48 h
      of storage times at 23  degrees C for all packaging treatments and a 2.1 log CFU/
      cm2 L. monocytogenes reduction at 72 h of storage time. PRACTICAL APPLICATIONS:
      Processors of kippered beef steak and turkey tenders could use a combination of
      vacuum or nitrogen-flushing or heat sealed with an oxygen scavenger packaging
      methods and a holding time of 24 h prior to shipping to reduce potential L.
      monocytogenes numbers by >=1 log. However, processors should be encouraged to
      hold packaged product a minimum of 72 h to enhance the margin of safety for L.
      monocytogenes control.

PMID- 22133034
TI  - Dorsal stream contributions to perceptual asymmetries.
AB  - Neurologically normal individuals show a bias toward the left side of space,
      referred to as pseudoneglect due to its similarity to clinical hemispatial
      neglect. The left bias appears to be stronger in the lower visual field during
      free-viewing, which could result from preferential dorsal stream processing. The
      current experiments used modified greyscales tasks, incorporating motion and
      isoluminant color, to explore whether targeting dorsal or ventral stream
      processing influenced the strength of the left bias. It was expected that the
      left bias would be stronger on the motion task than on a task incorporating
      isoluminant color. In Study 1, similar left biases were observed during prolonged
      viewing for luminance, motion and red, but not green color. The unexpected
      finding of a leftward bias for red under prolonged viewing was replicated in
      Study 2. A leftward bias for motion was also evident during 150 ms viewing in
      Study 2. In Study 3, the left bias was not apparent when using a blue/yellow
      condition, suggesting the left bias for red under prolonged viewing was likely
      unique to red. Furthermore, the leftward bias for red disappeared under brief
      viewing conditions. It is suggested that dorsal stream processing likely
      underlies visual field differences in pseudoneglect.

PMID- 22133035
TI  - Near-IR electrochromism in electropolymerized films of a biscyclometalated
      ruthenium complex bridged by 1,2,4,5-tetra(2-pyridyl)benzene.
AB  - Reductive electropolymerization of the biscyclometalated ruthenium complex
      [(vtpy)Ru(tpb)Ru(vtpy)](2+) [vtpy = 4'-vinyl-2,2':6',2"-terpyridine; tpb =
      1,2,4,5-tetra(2-pyridyl)benzene] proceeded smoothly on electrode surfaces. Thanks
      to the strong electron coupling between the ruthenium centers of the individual
      monomeric units and strong intervalence charge-transfer absorption in the mixed
      valence state, the produced adherent metallopolymeric films exhibited near-IR
      electrochromism with tricolor switching, good contrast ratio (40% at 1165 nm),
      short response time, low-switching voltage, and long memory time.

PMID- 22133036
TI  - The influence of methotrexate on the gene expression of the pro-inflammatory
      cytokine IL-12A in the therapy of rheumatoid arthritis.
AB  - OBJECTIVES: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid
      arthritis (RA). Among its anti-proliferative activity, the anti-inflammatory
      mechanisms of MTX seem to play a major role in the treatment of RA. MTX reduces
      the production of pro-inflammatory cytokines such as interleukin (IL)-1, IL-2, IL
      6 and interferon (INF)-gamma, while the gene expression of anti-inflammatory Th2
      cytokines like IL-4 and IL-10 is increased - altogether resulting in the anti
      inflammatory effect. As little is known about the impact of MTX on other
      cytokines involved in the pathogenesis of RA, the present trial investigated the
      effect of MTX on IL-12A and IL-18 gene expression by peripheral blood mononuclear
      cells (PBMCs). For comparison, the effect on IL-6 and tumour necrosis factor
      (TNF) was analysed. METHODS: Using real-time PCR, mRNA concentrations of pro
      inflammatory cytokines were determined in PBMCs from 17 patients before and
      during MTX therapy. Furthermore, gene expression was correlated with clinical and
      pharmacokinetic parameters such as methotrexate polyglutamate concentrations
      (Spearman's correlation coefficient). To eliminate concomitant corticosteroids as
      confounding factor, a subgroup analysis for methotrexate without corticosteroids
      was performed in 6 patients. RESULTS: MTX statistically significantly reduced the
      mRNA expression of IL-12A by PBMCs in rheumatoid arthritis patients (Wilcoxon
      test for paired samples, p<0.046). Consistent with other reports, IL-6 was
      reduced under MTX treatment. Although the combination of MTX and corticosteroids
      significantly reduced the gene expression of IL-18, this key molecule was
      unaffected by MTX without corticosteroids. Our results were further supported by
      a negative correlation of methotrexate polyglutamate concentrations and the mRNA
      expression of the pro-inflammatory cytokines IL-6 and IL-12A. CONCLUSIONS: We
      describe a novel effect of MTX reducing the gene expression of IL-12A
      independently of corticosteroid application in patients. This impact was further
      enhanced by a reduction of IL-12A-producing lymphocytes and neutrophils under MTX
      treatment. These results expand the understanding of the mechanism of action of
      the most widely used drug in RA.

PMID- 22133038
TI  - Solvent-resistant ultraflat gold using liquid glass.
AB  - Templating against atomically flat materials allows creation of smooth metallic
      surfaces. The process of adding the backing (superstrate) to the deposited metals
      has proven to be the most difficult part in producing reliable, large-area,
      solvent-resistant substrates and has been the subject of recent research. In this
      paper we describe a simple and inexpensive liquid glass template-stripping (lgTS)
      method for the fabrication of large area ultraflat gold surfaces. Using our lgTS
      method, ultraflat gold surfaces with normals aligned along the <111> crystal
      plane and with a root-mean-square roughness of 0.275 nm (over 1 MUm(2)) were
      created. The surfaces are fabricated on silica-based substrates which are highly
      solvent resistant and electrically insulating using silicate precursor solution
      (commonly known as "liquid glass") and concomitant mild heat treatment. We
      demonstrate the capabilities of such ultraflat gold surfaces by imaging nanoscale
      objects on top and fabricating microelectrodes as an example application. Because
      of the simplicity and versatility of the fabrication process, lgTS will have wide
      ranging application in imaging, catalysis, electrochemistry, and surface science.

PMID- 22133037
TI  - Health-related quality of life and treatment satisfaction in the Sensor-Augmented
      Pump Therapy for A1C Reduction 3 (STAR 3) trial.
AB  - OBJECTIVE: This study assessed health-related quality of life (HRQOL) and
      treatment satisfaction in sensor-augmented pump therapy (SAPT) compared with
      optimal conventional therapy-multiple daily injection (MDI) therapy with self
      monitoring of blood glucose (SMBG)-in adults and children with type 1 diabetes
      and children's caregivers. Patient acceptance of new therapies is essential to
      their adoption and effective use. RESEARCH DESIGN AND METHODS: STAR 3, a
      randomized 12-month clinical trial, compared SAPT with MDI+SMBG in 485 adult and
      pediatric patients. Within- and between-treatment arm changes in generic HRQOL,
      diabetes-specific HRQOL (fear of hypoglycemia), and treatment satisfaction were
      assessed (significance criterion P<0.01). RESULTS: In adults, children, and
      caregivers, there were no significant between-arm changes in generic HRQOL: SF-36
      Physical Component Summary and Mental Component Summary scores in adults and the
      PedsQL Physical Health Summary and Psychosocial Health Summary scores in children
      or caregivers. Diabetes-specific HRQOL (Hypoglycemia Fear Survey Worry and
      Behavior subscale scores) improved more in SAPT than in MDI adults. Hypoglycemia
      Behavior scores improved more in SAPT caregivers. Key treatment satisfaction
      measures (Insulin Delivery System Rating Questionnaire measures of Convenience,
      Efficacy, and Overall Preference) improved more in SAPT adults, children, and
      caregivers (all P<0.001); all exceeded the criterion for minimal detectable
      difference. CONCLUSIONS: In the first-ever large-scale study of SAPT compared
      with optimal conventional therapy, SAPT had significant advantages for
      hypoglycemia fear in adults and caregivers and for treatment satisfaction in
      adults, children, and caregivers.

PMID- 22133039
TI  - It's not just the television: survey analysis of sedentary behaviour in New
      Zealand young people.
AB  - BACKGROUND: Sedentary behaviour has been linked with adverse health outcomes in
      young people; however, the nature and context of being sedentary is poorly
      understood. Accurate quantification and description of sedentary behaviour using
      population-level data is required. The aim of this research was to describe
      sedentary behaviour among New Zealand (NZ) youth and examine whether sedentary
      behaviour differs by Body Mass Index (BMI) status in this population. METHODS: A
      national representative cross-sectional survey of young people aged 5-24 years (n
      = 2,503) was conducted in 2008-2009. Data from this survey, which included
      subjectively (recall diary; n = 1,309) and objectively (accelerometry; n = 960)
      measured sedentary behaviour for participants aged 10-18 years were analysed
      using survey weighted methods. RESULTS: Participants self-reported spending on
      average 521 minutes per day (standard error [SE] 5.29) in total sedentary
      behaviour, 181 minutes per day (SE 3.91) in screen-based sedentary activities
      (e.g., television and video games), and 340 minutes per day (SE 5.22) in other
      non-screen sedentary behaviours (e.g., school, passive transport and self-care).
      Accelerometer-measured total sedentary behaviour was on average 420 minutes per
      day (SE 4.26), or 53% (SE 0.42%) of monitored time. There were no statistically
      significant differences in time spent in sedentary behaviour among overweight,
      obese and healthy/underweight young people. CONCLUSIONS: Both subjective and
      objective methods indicate that NZ youth spend much of their waking time being
      sedentary. No relationships were found between sedentary behaviour and BMI
      status. These findings extend previous research by describing engagement in
      specific sedentary activities, as well as quantifying the behaviour using an
      objective method. Differences in what aspects of sedentary behaviour the two
      methods are capturing are discussed. This research highlights the potential for
      future interventions to target specific sedentary behaviours or demographic
      groups.

PMID- 22133040
TI  - Blood glucose testing and primary prevention of Type 2 diabetes-evaluation of the
      effect of evidence-based patient information: a randomized controlled trial.
AB  - AIMS: To compare the effect of our newly developed online evidence-based patient
      information vs. standard patient information about sub-threshold elevated blood
      glucose levels and primary prevention of diabetes on informed patient decision
      making. METHODS: We invited visitors to the cooperating health insurance company,
      Techniker Krankenkasse, and the German Diabetes Center websites to take part in a
      web-based randomized controlled trial. The population after randomization
      comprised 1120 individuals aged between 40 and 70 years without known diabetes,
      of whom 558 individuals were randomly assigned to the intervention group
      receiving evidence-based patient information, and 562 individuals were randomly
      assigned to the control group receiving standard information from the Internet.
      The primary endpoint was acquired knowledge of elevated blood glucose level
      issues and the secondary outcomes were attitude to metabolic testing, intention
      to undergo metabolic testing, decisional conflict and satisfaction with the
      information. RESULTS: Overall, knowledge of elevated glucose level issues and the
      intention to undergo metabolic testing were high in both groups. Participants who
      had received evidence-based patient information, however, had significantly
      higher knowledge scores. The secondary outcomes in the evidence-based patient
      information subgroup that completed the 2-week follow-up period yielded
      significantly lower intention to undergo metabolic testing, significantly more
      critical attitude towards metabolic testing and significantly higher decisional
      conflict than the control subgroup (n=466). Satisfaction with the information was
      not significantly different between both groups. CONCLUSIONS: Evidence-based
      patient information significantly increased knowledge about elevated glucose
      levels, but also increased decisional conflict and critical attitude to screening
      and treatment options. The intention to undergo metabolic screening decreased.
      Future studies are warranted to assess uptake of metabolic testing and
      satisfaction with this decision in a broader population of patients with unknown
      diabetes.

PMID- 22133041
TI  - Efficacy of lycopene against fluoride toxicity in rats.
AB  - CONTEXT: Oxidative damage to cellular components such as lipids and cell
      membranes by free radicals and reactive oxygen species (ROS) is thought to be
      associated with the development of degenerative diseases. Fluoride intoxication
      is associated with oxidative stress and altered anti-oxidant defense mechanism.
      Lycopene is a lipid-soluble powerful anti-oxidant that scavenges free radicals
      and ROS. OBJECTIVE: This study was extended to investigate lycopene anti-oxidant
      efficacy in different organs of fluoride-intoxicated rats. METHODS: Twenty-four
      adult rats were randomly divided into four groups of six animals each. Rats in
      group I received daily doses of vehicle. Group II rats were given lycopene (10
      mg/kg body weight/day), by tubes, dissolved in 0.5 ml of corn oil for 5 weeks.
      Group III rats were given sodium fluoride (NaF) (10.3 mg/kg body weight/day), by
      tubes, for 5 weeks. In group IV rats, lycopene was administered 1 h later and NaF
      was administered for 5 weeks. RESULTS: NaF administration induced oxidative
      stress as evidenced by elevated levels of lipid peroxidation (51.3, 65.9 and
      67.6%) measured as malondialdehyde and total nitrate/nitrite (61.0, 59.7 and
      68.9%) in red blood cells, heart and brain tissues. Moreover, significantly
      decreased reduced glutathione level, total anti-oxidant capacity and superoxide
      dismutase activity were observed in the examined tissues. The induced oxidative
      stress and the alterations in anti-oxidant system were normalized by the oral
      administration of lycopene treatment. CONCLUSION: Lycopene administration could
      minimize the toxic effects of fluoride indicating its free-radical scavenging and
      powerful anti-oxidant activities.

PMID- 22133042
TI  - Hydrophobicity and conformational change as mechanistic determinants for
      nonspecific modulators of amyloid beta self-assembly.
AB  - The link between many neurodegenerative disorders, including Alzheimer's and
      Parkinson's diseases, and the aberrant folding and aggregation of proteins has
      prompted a comprehensive search for small organic molecules that have the
      potential to inhibit such processes. Although many compounds have been reported
      to affect the formation of amyloid fibrils and/or other types of protein
      aggregates, the mechanisms by which they act are not well understood. A large
      number of compounds appear to act in a nonspecific way affecting several
      different amyloidogenic proteins. We describe here a detailed study of the
      mechanism of action of one representative compound, lacmoid, in the context of
      the inhibition of the aggregation of the amyloid beta-peptide (Abeta) associated
      with Alzheimer's disease. We show that lacmoid binds Abeta(1-40) in a surfactant
      like manner and counteracts the formation of all types of Abeta(1-40) and Abeta(1
      42) aggregates. On the basis of these and previous findings, we are able to
      rationalize the molecular mechanisms of action of nonspecific modulators of
      protein self-assembly in terms of hydrophobic attraction and the conformational
      preferences of the polypeptide.

PMID- 22133043
TI  - Pharmacotherapy alone vs endoscopic variceal ligation combination for secondary
      prevention of oesophageal variceal bleeding: meta-analysis.

PMID- 22133044
TI  - Air-stable heterobimetallic catalysts to effect Ni/Cr-mediated couplings with a
      ca. 1:1 molar ratio of coupling partners at low catalyst loadings.
AB  - Two air-stable Ni,Cr-heterobimetallic catalysts have been prepared from ligands 7
      and 11, obtained from scyllo-inositol in four and three steps, respectively. Both
      catalysts smoothly promote Ni/Cr-mediated coupling reactions with a ca. 1:1 molar
      ratio of coupling partners. The catalyst derived from 11 exhibits a better
      catalytic profile, thereby allowing Ni/Cr-mediated coupling reactions to be
      achieved with a wide range of substrates at a low catalyst loading in an
      operationally simple manner.

PMID- 22133045
TI  - Phylogenetic diversity, composition and distribution of bacterioplankton
      community in the Dongjiang River, China.
AB  - Bacterioplankton community compositions in the Dongjiang River were characterized
      using denaturing gradient gel electrophoresis (DGGE) and 16S rRNA gene clone
      library construction. Water samples in nine different sites were taken along the
      mainstem and three tributaries. In total, 24 bands from DGGE gels and 406 clones
      from the libraries were selected and sequenced, subsequently analyzed for the
      bacterial diversity and composition of those microbial communities. Bacterial 16S
      rRNA gene sequences from freshwater bacteria exhibited board phylogenetic
      diversity, including sequences representing the Alphaproteobacteria,
      Betaproteobacteria, Gammaproteobacteria, Actinobacteria, Bacteriodetes,
      Verrucomicrobia, and candidate division TM7. Members of Betaproteobacteria group
      were the most dominant in all sampling sites, followed by Gammaproteobacteria,
      Alphaproteobacteria, and Actinobacteria. DGGE profiles and the ?-LIBSHUFF
      analysis revealed similar patterns of bacterial diversity among most sampling
      sites, while spatial distribution variances existed in all sites along the river
      basin. Statistical analysis showed that bacterial species distribution strongly
      correlated with environmental variables, such as nitrate and ammonia, suggesting
      that nitrogen nutrients may shape the microbial community structure and
      composition in the Dongjiang River. This study had important implications for the
      comparison with other rivers elsewhere and contributed to the growing data set on
      the factors that structure bacterial communities in freshwater ecosystems.

PMID- 22133047
TI  - Mobility of capped silver nanoparticles under environmentally relevant
      conditions.
AB  - The mobility and deposition of capped silver (Ag) nanoparticles (NPs) on silica
      surfaces were characterized over a wide range of pH and ionic strength (IS)
      conditions, including seawater and freshwater. Two common organic capping agents
      (citrate and PVP) were evaluated. Both the capped Ag NPs and the silica surfaces
      were negatively charged under these environmentally relevant conditions,
      resulting in net repulsive electrostatics under most conditions. The steric
      repulsion introduced by the capping agents significantly reduced aggregation and
      deposition. In addition, the presence of natural organic matter in solution
      further decreased the deposition of either Ag NP on silica. Ag NPs were found to
      be highly mobile under these environmentally relevant conditions, with little or
      no deposition.

PMID- 22133046
TI  - Successful gene therapy in utero for lethal murine hypophosphatasia.
AB  - Hypophosphatasia (HPP), caused by mutations in the gene ALPL encoding tissue
      nonspecific alkaline phosphatase (TNALP), is an inherited systemic skeletal
      disease characterized by mineralization defects of bones and teeth. The clinical
      severity of HPP varies widely, from a lethal perinatal form to mild
      odontohypophosphatasia showing only dental manifestations. HPP model mice (Akp2(
      /-)) phenotypically mimic the severe infantile form of human HPP; they appear
      normal at birth but die by 2 weeks of age because of growth failure,
      hypomineralization, and epileptic seizures. In the present study, we investigated
      the feasibility of fetal gene therapy using the lethal HPP model mice. On day 15
      of gestation, the fetuses of HPP model mice underwent transuterine
      intraperitoneal injection of adeno-associated virus serotype 9 (AAV9) expressing
      bone-targeted TNALP. Treated and delivered mice showed normal weight gain and
      seizure-free survival for at least 8 weeks. Vector sequence was detected in
      systemic organs including bone at 14 days of age. ALP activities in plasma and
      bone were consistently high. Enhanced mineralization was demonstrated on X-ray
      images of the chest and forepaw. Our data clearly demonstrate that systemic
      injection of AAV9 in utero is an effective strategy for the treatment of lethal
      HPP mice. Fetal gene therapy may be an important choice after prenatal diagnosis
      of life-threatening HPP.

PMID- 22133048
TI  - Evaluation of overhead spray-applied sanitizers for the reduction of Salmonella
      on tomato surfaces.
AB  - Efficacy of sanitizers in an overhead spray and brush roller system was examined
      for reducing Salmonella on unwaxed, mature green tomatoes. Surface inoculated
      tomatoes were treated in the overhead spray system for 5, 15, 30, and 60 s. A
      sodium hypochlorite (NaOCl) study tested NaOCl (25, 50, and 100 mg/L) against a
      water control. A sanitizer study examined NaOCl (100 mg/L), chlorine dioxide
      (ClO2; 5 mg/L), peroxyacetic acid (PAA; 80 mg/L), and water. The overhead spray
      system was also compared to a scale-model flume. All NaOCl concentrations were
      significantly more effective at removing Salmonella than water and achieved at
      least a 3-log10 CFU/mL reduction at different treatment times (P < 0.05). NaOCl
      (100 mg/L) achieved a 4 +/- 1.8 log10 CFU/mL reduction at 15 s. In the sanitizer
      study, NaOCl, ClO2, and PAA achieved at least a 3-log10 CFU/mL reduction at 15 s
      and between 3.9 and 5.5 log10 CFU/mL reductions at 30 to 60 s. NaOCl (100 mg/L)
      in the overhead spray system significantly reduced more Salmonella than in the
      flume at 15 to 60 s. NaOCl flume treatment only reached a 1.3 +/- 1.1 log10
      CFU/mL reduction at 15 s. Results of this study demonstrate the ability of
      sanitizers in the laboratory model overhead spray system to reduce Salmonella on
      tomato surfaces. An overhead spray system could be implemented instead of flumes
      to achieve higher pathogen reduction with less water and sanitizer use, thereby
      lowering packing costs. PRACTICAL APPLICATION: The use of a non-recirculating,
      overhead spray brush roller system could offer a cost effective and efficacious
      way of washing tomatoes. The use large communal dump tanks in tomato processing
      has been suspected as a source of contamination in the tomato processing process.
      If effective, the brush roller system could augment or possible replace currently
      used dump tanks.

PMID- 22133049
TI  - Cauda equina hemangioblastoma at L5 vertebral level related to von Hippel-Lindau
      disease.
AB  - Hemangioblastoma (HB) is uncommon, with only a few cases of hemangioblastoma with
      von Hippel-Lindau disease (VHL) located in cauda equina previously reported. We
      describe a case of hemangioblastoma misdiagnosed as nerve sheath tumour in the
      cauda equina.

PMID- 22133050
TI  - Safety and tolerability of  extended-release niacin  with  laropiprant.
AB  - INTRODUCTION: Niacin is one of the oldest drugs used in the treatment of
      dyslipidemia. Previously its use has been limited because of excessive flushing.
      Now an agent laropiprant (LRP) has been developed, which blocks the flushing
      pathway. Therefore, it is time to collate available information to assess the
      safety and tolerability of combining niacin with LRP. AREAS COVERED: The authors
      searched PubMed and MEDLINE for literature published between January 2006 and
      July 2011, for safety and tolerability reports of extended-release niacin (ERN)
      with LRP. EXPERT OPINION: The addition of LRP to ERN, by reducing the side effect
      'flushing', may enable lipidologists and physicians to use niacin more widely as
      part of lipid modification therapy, especially since the combination can be
      safely added to statins. However, it has to be accepted that the addition of LRP
      does not completely abolish flushing. The favorable safety profile supports the
      use of LRP to achieve higher therapeutic dosing of niacin.

PMID- 22133051
TI  - Dietary factors and low-grade inflammation in relation to overweight and obesity.
AB  - Low-grade inflammation is a characteristic of the obese state, and adipose tissue
      releases many inflammatory mediators. The source of these mediators within
      adipose tissue is not clear, but infiltrating macrophages seem to be especially
      important, although adipocytes themselves play a role. Obese people have higher
      circulating concentrations of many inflammatory markers than lean people do, and
      these are believed to play a role in causing insulin resistance and other
      metabolic disturbances. Blood concentrations of inflammatory markers are lowered
      following weight loss. In the hours following the consumption of a meal, there is
      an elevation in the concentrations of inflammatory mediators in the bloodstream,
      which is exaggerated in obese subjects and in type 2 diabetics. Both high-glucose
      and high-fat meals may induce postprandial inflammation, and this is exaggerated
      by a high meal content of advanced glycation end products (AGE) and partly
      ablated by inclusion of certain antioxidants or antioxidant-containing foods
      within the meal. Healthy eating patterns are associated with lower circulating
      concentrations of inflammatory markers. Among the components of a healthy diet,
      whole grains, vegetables and fruits, and fish are all associated with lower
      inflammation. AGE are associated with enhanced oxidative stress and inflammation.
      SFA and trans-MUFA are pro-inflammatory, while PUFA, especially long-chain n-3
      PUFA, are anti-inflammatory. Hyperglycaemia induces both postprandial and chronic
      low-grade inflammation. Vitamin C, vitamin E and carotenoids decrease the
      circulating concentrations of inflammatory markers. Potential mechanisms are
      described and research gaps, which limit our understanding of the interaction
      between diet and postprandial and chronic low-grade inflammation, are identified.

PMID- 22133053
TI  - Isothermal ice crystallization kinetics in the gas-diffusion layer of a proton
      exchange-membrane fuel cell.
AB  - Nucleation and growth of ice in the fibrous gas-diffusion layer (GDL) of a proton
      exchange membrane fuel cell (PEMFC) are investigated using isothermal
      differential scanning calorimetry (DSC). Isothermal crystallization rates and
      pseudo-steady-state nucleation rates are obtained as a function of subcooling
      from heat-flow and induction-time measurements. Kinetics of ice nucleation and
      growth are studied at two polytetrafluoroethylene (PTFE) loadings (0 and 10 wt %)
      in a commercial GDL for temperatures between 240 and 273 K. A nonlinear ice
      crystallization rate expression is developed using Johnson-Mehl-Avrami-Kolmogorov
      (JMAK) theory, in which the heat-transfer-limited growth rate is determined from
      the moving-boundary Stefan problem. Induction times follow a Poisson distribution
      and increase upon addition of PTFE, indicating that nucleation occurs more slowly
      on a hydrophobic fiber than on a hydrophilic fiber. The determined nucleation
      rates and induction times follow expected trends from classical nucleation
      theory. A validated rate expression is now available for predicting ice
      crystallization kinetics in GDLs.

PMID- 22133052
TI  - Predictors of response to rituximab in patients with active rheumatoid arthritis
      and inadequate response to anti-TNF agents or traditional DMARDs.
AB  - OBJECTIVES: Identifying early predictors of response to biological agents is
      important for both the individual patient and health economics. The aim here was
      to identify clinical variables that are easily assessed in clinical practice
      which are associated with a major response to rituximab (moderate to good EULAR
      response, according to DAS28 values) in patients with active rheumatoid arthritis
      and inadequate response to anti-TNF agents or traditional DMARDs. METHODS:
      Rituximab (2x1g, two weeks apart) was administered to 108 patients in four
      different Spanish hospitals. The primary efficacy endpoint was the percentage of
      patients who achieved a major response at six months. Potential predictors of a
      major response were identified using multivariate binary logistic regression
      models. RESULTS: At six months of treatment 75.9% of patients achieved a major
      response (24% good and 52% moderate). Comparing the clinical features at baseline
      between patients who did or did not achieve a major response, significant
      differences were found in rheumatoid factor (RF) and anti-CCP positivity, as well
      as in the number of failed anti-TNF agents prior to rituximab. While rituximab
      delivers clinical benefit in seronegative patients, the presence of RF and/or
      anti-CCP consistently enriches clinical responses. The multivariate analysis
      showed that the best model for predicting a major EULAR response to rituximab was
      comprised of the following two variables: the anti-CCP antibody positivity
      (p=0.045) and the number of previous anti-TNF agents used (p=0.028). Using a cut
      off level for CCP of 300 U/ml we found that patients with an anti-CCP titre >300
      U/ml were 3-4 times more likely to achieve a major EULAR response [odds ratio
      (OR): 3.38; 95% CI: 1.025-11.17]. By contrast, those patients who had failed to
      respond to 2 or more anti-TNF agents had a 72.5% lower probability of achieving a
      moderate to good EULAR response (OR: 0.275; 95% CI: 0.087-0.871) than did
      patients who had only failed to respond to one such agent. CONCLUSIONS: A lower
      number of previously-failed TNF blockers and high anti-CCP titre can help select
      the best candidates for RTX therapy in patients with RA.

PMID- 22133055
TI  - The transfer from ewe to lamb of clostridial antibodies.
AB  - Abstract   Extract   Many farmers in New Zealand find it necessary to vaccinate
      their sheep flocks against certain of the clostridial diseases. Effective
      vaccines are available to protect sheep against the major scourges of blackleg,
      enterotoxaemia (pulpy kidney), malignant oedema, tetanus and black disease, but,
      to secure the full protective potential of each vaccine, it must be applied in
      the optimum fashion. This means using a potent vaccine, correctly administered to
      responsive sheep at such time before exposure that protection will have reached
      its peak when the challenge is encountered. It is generally accepted that such an
      ideal set of circumstances is only rarely achieved in the field.

PMID- 22133054
TI  - Astrocyte elevated gene-1 (AEG-1) is a marker for aggressive salivary gland
      carcinoma.
AB  - BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis
      and progression in diverse human cancers. The present study was aimed to
      investigate the clinical and prognostic significance of AEG-1 in salivary gland
      carcinomas (SGC). METHODS: Real-time PCR and western blot analyses were employed
      to examine AEG-1 expression in two normal salivary gland tissues, eight SGC
      tissues of various clinical stages, and five pairs of primary SGC and adjacent
      salivary gland tissues from the same patient. Immunohistochemistry (IHC) was
      performed to examine AEG-1 protein expression in paraffin-embedded tissues from
      141 SGC patients. Statistical analyses was applies to evaluate the diagnostic
      value and associations of AEG-1 expression with clinical parameters. RESULTS: AEG
      1 expression was evidently up-regulated in SGC tissues compared with that in the
      normal salivary gland tissues and in matched adjacent salivary gland tissues. AEG
      1 protein level was positively correlated with clinical stage (P < 0.001), T
      classification (P = 0.008), N classification (P = 0.008) and M classifications (P
      = 0.006). Patients with higher AEG-1 expression had shorter overall survival
      time, whereas those with lower tumor AEG-1 expression had longer survival time.
      CONCLUSIONS: Our results suggest that AEG-1 expression is associated with SGC
      progression and may represent a novel and valuable predictor for prognostic
      evaluation of SGC patients.

PMID- 22133056
TI  - Cyanide poisoning of cattle grazing "reed sweet-grass"
AB  - Abstract   Extract   Reed sweet-grass, Poa aquatica (Glyceria maxima, Glyceria
      acquatica), a member of the Gramineae family, is an introduced plant found in wet
      places in various localities in both the North and South Islands, but mainly in
      Otago and Southland (Allan,  1940 ). Garner ( 1961 , p. 318) quotes Quisumbine 
      (1947)  as listing 25 species belonging to the family Gramineae, including Poa
      aquatica, which contain hydrocyanic acid. Connor  (1951) , however, does not list
      Poa aquatica as one of the poisonous plants of New Zealand, and no previous
      references to poisoning by this plant have been found.

PMID- 22133057
TI  - Letters to the editor.

PMID- 22133058
TI  - Salmonellosis in young calves.

PMID- 22133059
TI  - The R3O+...H+ hydrogen bond: toward a tetracoordinate oxadionium(2+) ion.
AB  - Oxatriquinanes are tricyclic oxonium ions which are known to possess remarkable
      solvolytic stability compared to simple alkyl oxonium salts. Their rigid,
      hemispherical structure presents an oxygen at the apex of three fused five
      membered rings. While trivalent oxygen species like these have been well
      described in the literature, the ability of oxygen to enter into a fourth
      covalent bonding relationship has been visited in theory and suggested by the
      outcome of certain reactions conducted in superacidic media, but has never been
      established by the characterization of a stable, persistent R(3)OH(2+) or
      R(4)O(2+) ion. In this study, the nucleophilicity of the oxatriquinane oxygen was
      evaluated first by a series of protonation studies using the Bronsted superacid
      H(CHB(11)Cl(11)) both in the solid state and in liquid HCl solution. The
      interaction of the oxatriquinane oxygen with a bridging carbocation was also
      examined. A strong case could be made for the occurrence of hydrogen bonding
      between H(CHB(11)Cl(11)) and oxatriquinane using IR spectroscopy. Under the most
      forcing protonation conditions, the oxatriquinane ring is cleaved to give a
      bridged, dicationic, protonated tetrahydrofuran-carbenium ion.

PMID- 22133060
TI  - Influence of Emblica officinalis aqueous extract on growth and antioxidant
      defense system of human hepatoma cell line (HepG2).
AB  - CONTEXT: Amla [Emblica officinalis Gaertn. (Euphorbiaceae)], a major constituent
      of several herbal formulations, is a well-known hepatoprotectant. Despite its
      extensive use, mechanistic understanding of its antioxidant action is rather
      limited. OBJECTIVE: In the current study, we investigated the effects of E.
      officinalis extracts (from dried fruits) on cellular oxidative state using a
      hepatocyte cell line (HepG2). We hypothesize that E. officinalis aqueous extracts
      have potency to modulate basal oxidative markers and enhance endogenous
      antioxidant defenses. MATERIALS AND METHODS: Cells were incubated with aqueous
      extracts of E. officinalis (1-100 MUg/ml) for varied time points (4-24 h) and
      biochemical markers of oxidative stress were determined in cell lysate.
      DISCUSSION: Aqueous extracts of E. officinalis at 100 MUg/ml can significantly
      modulate the basal levels of oxidative markers and enhance antioxidant defenses
      of the cells. CONCLUSIONS: Our findings clearly indicate the propensity of E.
      officinalis aqueous extracts to improve endogenous antioxidant defenses in HepG2
      cells. Although further studies are required to assess their efficacy under
      experimentally induced oxidative, our data suggest that the hepatoprotective
      effects of E. officinalis reported earlier may be largely due to its potential to
      enhance the antioxidant defenses in vivo. RESULTS: Because E. officinalis up to
      100 MUg/ml concentrations had no effect on cell viability; it was considered
      noncytotoxic. Incubation with E. officinalis for 24 h resulted in significant
      diminution in the levels of lipid hydroperoxide (18-42%) and reactive oxygen
      species (11-29%). Furthermore; E. officinalis increased the levels of glutathione
      (GSH; 18-32%); antioxidant capacity (19-31%); and activities of antioxidant
      enzymes (superoxide dismutase; 25-41%; catalase; 39-50%; GSH peroxidase; 20-35%;
      GSH reductase; 26-35%; and GSH S-transferase; 12-30%).

PMID- 22133061
TI  - Composition of humic acid-degrading estuarine and marine bacterial communities.
AB  - We examined the bacterial decomposition of humic acids (HA) in two flow-through
      culture experiments, one inoculated by marine and one by estuarine bacterial
      communities. In both experiments, the cultures were fed with HA media of
      salinities of 28 and 14, close to their ambient and a distinctly different,
      foreign salinity. HA were decomposed to > 60% of the initial concentration within
      70 days, and the foreign salinity yielded the highest decomposition. A detrended
      correspondence analysis of denaturing gradient gel electrophoresis (DGGE) banding
      patterns showed that during incubation, the bacterial community composition
      underwent distinct changes. A phylogenetic analysis of DGGE bands excised and
      bacteria isolated at the end on HA as the sole carbon source showed that
      Alphaproteobacteria and Gammaproteobacteria largely dominated the communities in
      the marine flow-through cultures, whereas Gammaproteobacteria, Actinobacteria and
      Alphaproteobacteria dominated the estuarine communities. Eleven of 13 isolates
      obtained from both experiments were able to grow on HA as the sole carbon source,
      seven on phenol and three, affiliated to the Roseobacter clade, on various
      aromatic acids. The bacteria retrieved from the flow-through cultures were
      closely (96-99%) affiliated to organisms capable of degrading humic matter,
      aromatic and aliphatic compounds and also to other bacteria reported previously
      from the Wadden Sea and Weser estuary.

PMID- 22133062
TI  - The effect of varying stimulus phase between frequency and amplitude modulation
      on auditory steady-state responses in neonates.
AB  - OBJECTIVE: To compare auditory steady-state responses (ASSRs) to air-conducted
      amplitude, frequency, and mixed modulated stimuli (AM, FM, and MM, respectively)
      in neonates. DESIGN: Multiple ASSRs to AM, FM, and MM to 0.5, 1, 2, and 4 kHz
      tones modulated between 0.078 and 0.092 kHz were recorded and compared. MM phase
      settings across the cycle at 45 degrees  intervals were used and optimum phase
      settings were predicted using a sinusoidal model. STUDY SAMPLE: Twenty neonates
      with click ABR thresholds of <= 40 dB nHL. RESULTS: ASSR amplitudes were
      significantly larger to AM than FM stimuli. MM phase setting had a significant
      effect on amplitude at 1, 2, and 4 kHz but not 0.5 kHz. MM phase settings (+/-
      95% confidence intervals) of 276 degrees  (+/- 9.5 degrees ) and 270 degrees  (+/
      19.1 degrees ) were predicted for 1 and 2 kHz, respectively. The 0.5 and 4 kHz
      data were not sufficient to model any effect of phase. MM and AM response
      latencies increased with decreasing carrier frequency. Some MM response latencies
      were significantly different from AM response latencies, however no consistent
      trend was apparent. Test times were significantly affected by phase setting.
      CONCLUSIONS: MM phase settings have a significant effect on ASSR response
      amplitude and latencies in neonates.

PMID- 22133063
TI  - Evaluation of long-term patient satisfaction and experience with the Baha(r) bone
      conduction implant.
AB  - OBJECTIVE: Evaluate long-term patient satisfaction with bone-anchored hearing
      aids (the Baha(r), now referred to by Cochlear as a 'bone conduction implant') in
      our hospital clinic spanning the eighteen-year period from the inception of our
      Baha program. The researchers further wished to analyse the various factors
      leading to patient satisfaction/dissatisfaction with their Baha. We developed a
      new questionnaire to obtain a comprehensive impression of individual patient
      practices, general satisfaction, and experiences with their Baha in respect to
      time spent using Baha, sound quality, annoyance from noise disturbance, ease of
      communication, cosmetic appearance, and satisfaction with the Baha amongst
      patient relatives, an aspect not previously investigated. DESIGN: The study
      design was retrospective and executed as a postal questionnaire. The
      questionnaire was developed by the authors of this paper. STUDY SAMPLE: Patients
      operated on for a Baha at our hospital from 1989 to 2007. RESULTS: The response
      rate was 92.4%. Eighty-six percent were satisfied or very satisfied with their
      Baha. Ninety-one percent of respondents could communicate using their Baha in a
      one-on-one conversational setting. A primary factor leading to dissatisfaction,
      experienced by 70% of responding patients, was annoyance from wind noise.
      CONCLUSIONS: Baha was found to yield good overall patient satisfaction over the
      long-term, and it was possible to identify specific factors attributing to
      satisfaction/dissatisfaction.

PMID- 22133064
TI  - Targeting PDGFR-beta in Cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinomas (CCAs) are highly desmoplastic neoplasms with a
      tumour microenvironment plentiful in myofibroblasts (MFBs). MFB-derived PDGF-BB
      survival signalling is a mediator of CCA cell resistance to apoptotic stimuli.
      This raises the concept that targeting PDGFR-beta, a cognate receptor of PDGF-BB,
      represents a potential strategy for the treatment of human CCA. AIMS: Herein, we
      examine a role for inhibiting PDGFR-beta in restoring CCA cell sensitivity to
      apoptotic stimuli in vitro and in vivo. METHODS: We employed human CCA samples
      from 41 patients (19 intrahepatic and 22 extrahepatic CCA samples), the human CCA
      cell lines KMCH-1 and HUCCT-1 as well as shPDGFR-beta-KMCH-1 and human
      myofibroblastic LX-2 cells for these studies. In vivo-experiments were conducted
      using a syngeneic rat orthotopic CCA model. RESULTS: Of several MFB-derived
      growth factors profiled, PDGF-BB and CTGF were most abundantly expressed;
      however, only PDGF-BB attenuated tumour necrosis factor-related apoptosis
      inducing ligand (TRAIL) cytotoxicity. Co-culturing CCA cells with PDGF-BB
      secreting MFBs significantly decreased TRAIL-induced CCA cell apoptosis when
      compared with monoculture conditions; this cytoprotective effect was abrogated in
      the presence of the tyrosine kinase inhibitors imatinib mesylate or linifanib,
      which inhibit PDGFR-beta. Consistent with these findings, MFB-imparted
      cytoprotection also was abolished when PDGFR-beta was knocked down as
      demonstrated in shPDGFR-beta-KMCH-1 cells. Finally, administration of imatinib
      mesylate increased CCA cell apoptosis and reduced tumour growth in a rodent in
      vivo-CCA model that mimics the human disease. CONCLUSIONS: Targeting PDGFR-beta
      sensitizes CCA cells to apoptotic stimuli and appears to be therapeutic in vivo.

PMID- 22133065
TI  - Collective domino approach toward the core of molecules isolated from the genus
      Schisandra.
AB  - A concise route to the ABC and ABCD core of molecules isolated from the genus
      Schisandra has been accomplished. The synthesis demonstrated high atom efficiency
      employing a new one-pot cascade which sequentially built three rings and a
      quaternary spirocenter.

PMID- 22133066
TI  - Serum metabonomics study of adenine-induced chronic renal failure in rats by
      ultra performance liquid chromatography coupled with quadrupole time-of-flight
      mass spectrometry.
AB  - An ultra performance liquid chromatography coupled with quadrupole time-of-flight
      mass spectrometry (UPLC Q-TOF MS) metabonomics approach was employed to study the
      serum metabolic profiling of adenine-induced chronic renal failure (CRF) rats.
      Acquired data were subjected to principal component analysis (PCA) for
      differentiating the CRF and the normal control groups. Potential biomarkers were
      screened by using S-plot and were identified by the accurate mass, isotopic
      pattern and MS/MS fragments information obtained from UPLC Q-TOF MS analysis.
      Significant differences in the serum level of creatinine, amino acids and LysoPCs
      were observed, indicating the perturbations of amino acid metabolism and
      phospholipid metabolism in adenine-induced CRF rats. This research proved that
      metabonomics is a promising tool for disease research.

PMID- 22133067
TI  - Quality parameters and antioxidant and antibacterial properties of some Mexican
      honeys.
AB  - A total of 14 Mexican honeys were screened for quality parameters including
      color, moisture, proline, and acidity. Antioxidant properties of complete honey
      and its methanolic extracts were evaluated by the DPPH, ABTS, and FRAP assays. In
      addition, the antimicrobial activity of complete honeys against Bacillus cereus
      ATCC 10876, Listeria monocytogenes Scott A, Salmonella Typhimurium ATCC 14028,
      and Sthapylococcus aureus ATCC 6538 was determined. Most of honeys analyzed
      showed values within quality parameters established by the Codex Alimentarius
      Commission in 2001. Eucalyptus flower honey and orange blossom honey showed the
      highest phenolic contents and antioxidant capacity. Bell flower, orange blossom,
      and eucalyptus flower honeys inhibited the growth of the 4 evaluated
      microorganisms. The remaining honeys affected at least 1 of the estimated growth
      parameters (increased lag phase, decreased growth rate, and/or maximum population
      density). Microorganism sensitivity to the antimicrobial activity of honeys
      followed the order B. cereus > L. monocytogenes > Salmonella Typhimurium > S.
      aureus. The monofloral honey samples from orange blossoms, and eucalyptus flowers
      demonstrated to be good sources of antioxidant and antimicrobial compounds. All
      the Mexican honey samples examined proved to be good sources of antioxidants and
      antimicrobial agents that might serve to maintain health and protect against
      several diseases. PRACTICAL APPLICATION: The results of the study showed that
      Mexican honeys display good quality parameters and antioxidant and antimicrobial
      activities. Mexican honey can be used as an additive in the food industry to
      increase the nutraceutical value of products.

PMID- 22133068
TI  - Cu4I4 clusters supported by P^N-type ligands: new structures with tunable
      emission colors.
AB  - A series of Cu(4)I(4) clusters (1-5) supported by two P^N-type ligands 2
      [(diRphosphino)methyl]pyridine (1, R = phenyl; 2, R = cyclohexyl; 3, R = tert
      butyl; 4, R = iso-propyl; 5, R = ethyl) have been synthesized. Single crystal X
      ray analyses show that all five clusters adopt a rare "octahedral" geometry. The
      central core of the cluster consists of the copper atoms arranged in a
      parallelogram with MU(4)-iodides above and below the copper plane. The copper
      atoms on the two short edges of the parallelogram (Cu-Cu = 2.525(2)-2.630(1) A)
      are bridged with MU(2)-iodides, whereas the long edges (Cu-Cu = 2.839(3)-3.035(2)
      A) are bridged in an antiparallel fashion by the P^N ligands. This Cu(4)I(4)
      geometry differs significantly from the "cubane" and "stairstep" geometries
      reported for other Cu(4)I(4)L(4) clusters. Luminescence spectra of clusters 3 and
      4 display a single emission around 460 nm at room temperature that is assigned to
      emission from a triplet halide-to-ligand charge-transfer ((3)XLCT) excited state,
      whereas clusters 1, 2, and 5 also have a second band around 570 nm that is
      assigned to a Cu(4)I(4) cluster-centered ((3)CC) excited state. The structural
      and photophysical properties of a dinuclear Cu(2)I(2)(P^N)(2) complex obtained
      during the sublimation of cluster 3 is also provided.

PMID- 22133069
TI  - Average orientation of a molecular rotor embedded in a Langmuir-Blodgett
      monolayer.
AB  - A molecular rotor in which a naphthalene rotator is attached through a silicon
      atom to three fatty acid chains has been synthesized, and Langmuir-Blodgett
      techniques were used to deposit on silica surfaces monolayers of its calcium
      salt, both neat and diluted with stearic acid salts. The monolayer films have
      been characterized by ellipsometry and Fourier transform infrared (FT-IR) grazing
      incidence attenuated total internal reflection (GATR) spectroscopy on Si-SiO(2)
      and by UV-vis absorption spectroscopy on SiO(2). The measurements were combined
      with calculations of the electronic (INDO/S) and vibrational (DFT) transition
      moment directions to deduce the average orientation of the rotor molecules,
      including the naphthalene ring, relative to the surface. In both neat and mixed
      films, the naphthalene ring is found to preferentially tilt toward the surface,
      enough that its rotation is most likely hindered. A comparable picture was
      obtained from molecular mechanics calculations on a mixed film of the naphthalene
      rotor and stearic acid.

PMID- 22133070
TI  - Editorial Note.
AB  - Abstract   In the article "Experimental infection of the possum (Trichosurus
      vulpecula) with Leptospira interrogans serovar balcanica. I. A comparison of
      laboratory techniques for the detection of leptospiraemia and leptospiruria" by
      S. C. Hathaway (N.Z.vet.J.29: 121-5) Tables II and III did not relate to the
      text. All reprints of this article will contain the correct Tables.

PMID- 22133071
TI  - Parasites of Chamois in New Zealand.
AB  - Abstract   Sir, - Andrews'((2)) checklist of helminth parasites of wild ruminants
      in New Zealand recorded the presence of 10 species of gastrointestinal nematodes
      in chamois (Rupicapra rupicapra rupicapra L.) from "Central South Island". In
      October 1978 we examined 28 freshly-shot chamois cadavers from the Harper-Avoca
      watershed in the headwaters of the Rakaia River. Six of the nematode species
      reported by Andrews were found again; viz. Ostertagia ostertagi, O. circumcincta,
      O. trifurcata, Nematodirus filicollis, Oesophagostomum venulosum and Trichuris
      ovis. The 4 species found by Andrews that were not recovered by us from the
      animals we examined were: Trichostrongylus axei, T. vitrinus, Spiculotragia
      spiculoptera and S. asymmetrica. On the other hand we found 4 helminths not
      encountered by Andrews: 3 nematodes: Nematodirus spathiger (Railliet, 1896), N.
      abnormalis (May, 1920), and Chabertia ovina (Fabricius, 1794), and 7 specimens of
      the cestode Moniezia expansa (Rud., 1805). Nematodirus spathiger was the most
      commonly encountered Nematodirus species, but generally the numbers of all 3
      species encountered were low as might be expected in a sample of adult and almost
      year-old animals. It is probable that most of the adults had acquired some
      measure of immunity((3)), and the most susceptible group, the kids, would not be
      born until late November. Because peptic digestion was not used to recover
      juveniles from the intestinal submucosa, only small numbers of adults were
      obtained.

PMID- 22133072
TI  - Therapeutic consequences of crystals in the synovial fluid: a review for
      clinicians.
AB  - Many crystals may be found in arthritic joints. Rheumatologists are able to
      diagnose, with a high degree of probability, which crystals induce arthritis in
      the individual case. A definite diagnosis supported by polarisation microscopy
      may provide a firm basis for adequate long-term treatment. Recently new insights
      in the inflammatory processes induced the development of targeted therapies. We
      review novel developments in crystal-induced arthritis and gout in particular.

PMID- 22133073
TI  - EPR analysis and DFT computations of a series of polynitroxides.
AB  - Polynitroxides with varying numbers of nitroxide groups (one to four) derived
      from different aromatic core structures show intramolecular electron spin-spin
      coupling. The scope of this study is to establish an easy methodology for
      extracting structural, dynamical, and thermodynamical information from the EPR
      spectra of these polynitroxides which might find use as spin probes in complex
      systems, such as biological and host/guest systems, and as polarizing agents in
      dynamic nuclear polarization (DNP) applications. Density functional theory (DFT)
      calculations at the B3LYP/6-31G(d) level provided information on the structural
      details such as bond lengths and angles in the gas phase, which were compared
      with the single crystal X-ray diffraction data in the solid state. Polarizable
      continuum model (PCM) calculations were performed to account for solvent
      influences. The electron paramagnetic resonance (EPR) spectra of the
      polynitroxides in chloroform were analyzed in detail to extract information such
      as the percentages of different conformers, hyperfine coupling constants a, and
      rotational correlation times tau(c). The temperature dependence on the line shape
      of the EPR spectra gave thermodynamic parameters DeltaH and DeltaS for the
      conformational transitions. These parameters were found to depend on the number
      and relative positions of the nitroxide and other polar groups.

PMID- 22133074
TI  - In vitro digestion enhances anti-adhesion effect of tempe and tofu against
      Escherichia coli.
AB  - AIMS:   Enterotoxigenic Escherichia coli is one of the main pathogenic bacteria
      causing diarrhoea. Earlier studies have shown that tempe-a fungal fermented soya
      food-has anti-adhesive activity against E. coli in vitro. Our aims were to
      challenge the anti-adhesive activity under gastro-intestinal conditions and to
      assess the activity of the nonfermented soya product tofu. METHODS AND RESULTS:  
      In this study, we compared the anti-adhesive activity of two major soya bean
      products, tempe and tofu, and their ileum efflux after transit through a dynamic
      gastrointestinal system simulating digestion in the human stomach and small
      intestine. The results showed that both tempe and tofu have an anti-adhesive
      activity against E. coli in vitro. Tempe and tofu, after digestion through the
      stomach and small intestine, have even higher anti-E. coli adhesive activity.
      CONCLUSIONS:   In addition to the proven in-vivo activity of tempe, this confirms
      the potential antidiarrhoeal effect of both the soya products tempe and tofu.
      SIGNIFICANCE AND IMPACT OF THE STUDY:   As tofu has a much greater circle of
      consumers, this finding is relevant for the health of a large part of the world's
      population.

PMID- 22133075
TI  - Anti-snake venom activities of extracts and fractions from callus cultures of
      Sapindus saponaria.
AB  - CONTEXT: Sapindus saponaria L. (Sapindaceae) bark, root, and fruits are used as
      sedatives and to treat gastric ulcer and also demonstrate diuretic and
      expectorant effects. OBJECTIVE: The anti-snake venom properties of callus of S.
      saponaria are investigated here for the first time. MATERIALS AND METHODS: In
      vitro cultivated callus of Sapindus saponaria were lyophilized, and the extracts
      were prepared with different solvents, before submitting to phytochemical studies
      and evaluation of the anti-ophidian activity. Crude extracts were fractionated by
      liquid-liquid partition and the fractions were monitored by thin layer
      chromatography (TLC). Subsequently, anti-ophidian activities were analyzed toward
      Bothrops jararacussu Lacerda (Viperidae), B. moojeni Hoge (Viperidae), B.
      alternates Dumeril (Viperidea) and Crotalus durissus terrificus Lineu (Viperidae)
      venoms and isolated myotoxins and phospholipase A(2) (PLA(2)). RESULTS: Fractions
      A1, A2 and the extract in MeOH:H(2)O (9:1) significantly inhibited the toxic and
      pharmacological activities induced by snake venoms and toxins, when compared to
      other extracts and fractions. The lethal, clotting, phospholipase, edema
      inducing, hemorrhagic and myotoxic activities were partially inhibited by the
      different extracts and fractions. TLC profiles of the crude extracts (B and C)
      and fractions (A1 and A2) showed beta-sitosterol and stigmasterol as their main
      compounds. Stigmasterol exhibited inhibitory effects on enzymatic and myotoxic
      activities of PLA(2). DISCUSSION AND CONCLUSION: Sapindus saponaria extracts and
      fractions presented anti-ophidian activity and could be used as an adjuvant to
      serum therapy or for its supplementation, and in addition, as a rich source of
      potential inhibitors of enzymes involved in several pathophysiological human and
      animal diseases.

PMID- 22133076
TI  - Personalized medicine: a patient-centered paradigm.

PMID- 22133077
TI  - Integrating medicinal chemistry, organic/combinatorial chemistry, and
      computational chemistry for the discovery of selective estrogen receptor
      modulators with Forecaster, a novel platform for drug discovery.
AB  - As part of a large medicinal chemistry program, we wish to develop novel
      selective estrogen receptor modulators (SERMs) as potential breast cancer
      treatments using a combination of experimental and computational approaches.
      However, one of the remaining difficulties nowadays is to fully integrate
      computational (i.e., virtual, theoretical) and medicinal (i.e., experimental,
      intuitive) chemistry to take advantage of the full potential of both. For this
      purpose, we have developed a Web-based platform, Forecaster, and a number of
      programs (e.g., Prepare, React, Select) with the aim of combining computational
      chemistry and medicinal chemistry expertise to facilitate drug discovery and
      development and more specifically to integrate synthesis into computer-aided drug
      design. In our quest for potent SERMs, this platform was used to build virtual
      combinatorial libraries, filter and extract a highly diverse library from the NCI
      database, and dock them to the estrogen receptor (ER), with all of these steps
      being fully automated by computational chemists for use by medicinal chemists. As
      a result, virtual screening of a diverse library seeded with active compounds
      followed by a search for analogs yielded an enrichment factor of 129, with 98% of
      the seeded active compounds recovered, while the screening of a designed virtual
      combinatorial library including known actives yielded an area under the receiver
      operating characteristic (AU-ROC) of 0.78. The lead optimization proved less
      successful, further demonstrating the challenge to simulate structure activity
      relationship studies.

PMID- 22133078
TI  - Optimization and validation of an extraction method for the analysis of
      polycyclic aromatic hydrocarbons in chocolate candies.
AB  - Chocolate is a key ingredient in many foods such as milk shakes, candies, bars,
      cookies, and cereals. Chocolate candies are often consumed by mankind of all age
      groups. The presence of polycyclic aromatic hydrocarbons (PAHs) in chocolate
      candies may result in health risk to people. A rapid, precise, and economic
      extraction method was optimized and validated for the simultaneous determination
      of polycyclic aromatic hydrocarbons in chocolate candy by high-performance liquid
      chromatography (HPLC) and gas chromatography-mass spectrometry (GS-MS) as a
      confirmatory technique. The method was optimized by using different solvents for
      liquid-liquid extraction, varying volume of de-emulsifying agent, and quantity of
      silica gel used for purification. The HPLC separation of 16 PAHs was carried out
      by C-18 column with mobile phase composed of acetonitrile : water (70 : 30) in
      isocratic mode with runtime of 20 min. Limit of detection, limit of
      quantification (LOQ), and correlation coefficients were found in the range of 0.3
      to 4 ng g-1, 0.9 to 12 ng g-1, and 0.9109 to 0.9952, respectively. The
      exploration of 25 local chocolate candy samples for the presence of PAHs showed
      the mean content of benzo[a]pyrene as 1.62 ng g-1, which representing the need to
      evaluate effective measures to prevent more severe PAHs contamination in
      chocolate candies in future. PRACTICAL APPLICATION: Chocolate is one of the most
      favorite food items among people, especially children. Chocolate candies are
      often consumed by mankind of all age groups. Chocolate candies are often consumed
      by children in large quantities. The presence PAHs in chocolate candies may
      result in health risk to people. In the present study, a precise and cost
      effective rapid method was employed for the determination of PAHs, which can be
      employed for daily routine analysis of PAHs in chocolate products.

PMID- 22133079
TI  - Enhanced growth and bioconversion of isoflavones in prebiotic-soymilk fermented
      by UV-treated lactobacilli and bifidobacteria.
AB  - The aim of this study was to evaluate the effects of ultraviolet (UV) radiation
      (ultraviolet A (UVA), ultraviolet B (UVB) and ultraviolet C (UVC) at 30-90 J/m2)
      on the membrane properties of lactobacilli and bifidobacteria, and their
      bioconversion of isoflavones in prebiotic-soymilk. UV treatment caused membrane
      permeabilization and alteration at the acyl chain, polar head and interface
      region of membrane bilayers via lipid peroxidation. Such alteration subsequently
      led to decreased (p < 0.05) viability of lactobacilli and bifidobacteria
      immediately after the treatment. However, the effect was transient where cells
      treated with UV, particularly UVA, grew better in prebiotic-soymilk than the
      control upon fermentation at 37 degrees C for 24 h (p < 0.05). In addition, UV
      treatment also increased (p < 0.05) the intracellular and extracellular beta
      glucosidase activity of lactobacilli and bifidobacteria. This was accompanied by
      an increased (p < 0.05) bioconversion of glucosides to bioactive aglycones in
      prebiotic-soymilk. Our present study illustrated that treatment of lactobacilli
      and bifidobacteria with UV could develop a fermented prebiotic-soymilk with
      enhanced bioactivity.

PMID- 22133080
TI  - Determining charge transport pathways through single porphyrin molecules using
      scanning tunneling microscopy break junctions.
AB  - Charge transport in a porphyrin with four identical pyridyl substituents,
      5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine (TPyP), was investigated using the
      scanning tunneling microscopy break junction method. To determine the dominant
      pathway, we studied two structurally similar porphyrins, o-DPyP and p-DPyP. Our
      experiments reveal that charge transport through TPyP in a break junction
      configuration does not follow the traditional assumption, i.e., the shortest path
      between the neighboring side groups. Instead, the charge transport pathway was
      dominated by the farthest anchoring groups. Furthermore, these single molecule
      experiments can distinguish between the two structural isomers, which is
      important in molecular discrimination, porphyrin chemistry, and molecular
      electronics.

PMID- 22133082
TI  - Methodological considerations in studying natural history of HBeAg-negative and 
      positive chronic hepatitis B.

PMID- 22133083
TI  - A practical synthetic route to enantiopure 6-substituted cis-decahydroquinolines.
AB  - Starting from 4-substituted cyclohexanones, a practical synthetic route to
      enantiopure 6-substituted cis-decahydroquinolines has been developed, the key
      steps being a stereoselective cyclocondensation of an unsaturated delta-keto
      ester derivative with (R)-phenylglycinol and the stereoselective hydrogenation of
      the resulting tricyclic oxazoloquinolone lactams.

PMID- 22133084
TI  - A homologous series of cobalt, rhodium, and iridium metalloradicals.
AB  - We herein present a series of d(7) trimethylphosphine complexes of group 9 metals
      that are chelated by the tripodal tetradentate tris(phosphino)silyl ligand
      [SiP(iPr)(3)]H ([SiP(iPr)(3)] = (2-iPr(2)PC(6)H(4))(3)Si(-)).  Both electron
      paramagnetic resonance (EPR) simulations and density functional theory (DFT)
      calculations indicate largely metalloradical character. These complexes provide a
      rare opportunity to compare the properties between the low-valent metalloradicals
      of the second- and third-row transition metals with the corresponding first-row
      analogues.

PMID- 22133086
TI  - High pressure ESR studies of electron self-exchange reactions of organic radicals
      in solution.
AB  - Simple electron self-exchange reactions are often used to study the role of the
      reaction medium on a chemical process, commonly implying the use of various
      solvents with different physical properties. In principle, similar studies may be
      conducted using a single solvent, changing its physical properties by application
      of elevated pressures, but so far only little information is available on
      pressure dependent exchange reactions. In this work, we have used a recently
      constructed high pressure apparatus for use with electron spin resonance (ESR)
      spectroscopy to investigate simple electron self-exchange reactions involving 2,3
      dichloro-5,6-dicyanobenzoquinone (DDQ) and tetracyanoethylene (TCNE) and their
      respective radical anions as well as TMPPD and its radical cation in three
      different solvents. The self-exchange was observed by ESR line broadening
      experiments, yielding rate constants and volumes of activation. The experimental
      results were compared to theoretical calculations based on Marcus theory and
      taking into account solvent dynamic effects. The use of elevated pressures has
      enabled the study of solvent effects without commonly encountered problems like
      solubility issues or chemical reactions between solvent and solute which
      sometimes limit the range of useable solvents.

PMID- 22133085
TI  - Relative impact of key sources of systematic noise in Affymetrix and Illumina
      gene-expression microarray experiments.
AB  - BACKGROUND: Systematic processing noise, which includes batch effects, is very
      common in microarray experiments but is often ignored despite its potential to
      confound or compromise experimental results. Compromised results are most likely
      when re-analysing or integrating datasets from public repositories due to the
      different conditions under which each dataset is generated. To better understand
      the relative noise-contributions of various factors in experimental-design, we
      assessed several Illumina and Affymetrix datasets for technical variation between
      replicate hybridisations of Universal Human Reference (UHRR) and individual or
      pooled breast-tumour RNA. RESULTS: A varying degree of systematic noise was
      observed in each of the datasets, however in all cases the relative amount of
      variation between standard control RNA replicates was found to be greatest at
      earlier points in the sample-preparation workflow. For example, 40.6% of the
      total variation in reported expressions were attributed to replicate extractions,
      compared to 13.9% due to amplification/labelling and 10.8% between replicate
      hybridisations. Deliberate probe-wise batch-correction methods were effective in
      reducing the magnitude of this variation, although the level of improvement was
      dependent on the sources of noise included in the model. Systematic noise
      introduced at the chip, run, and experiment levels of a combined Illumina dataset
      were found to be highly dependent upon the experimental design. Both UHRR and
      pools of RNA, which were derived from the samples of interest, modelled technical
      variation well although the pools were significantly better correlated (4%
      average improvement) and better emulated the effects of systematic noise, over
      all probes, than the UHRRs. The effect of this noise was not uniform over all
      probes, with low GC-content probes found to be more vulnerable to batch variation
      than probes with a higher GC-content. CONCLUSIONS: The magnitude of systematic
      processing noise in a microarray experiment is variable across probes and
      experiments, however it is generally the case that procedures earlier in the
      sample-preparation workflow are liable to introduce the most noise. Careful
      experimental design is important to protect against noise, detailed meta-data
      should always be provided, and diagnostic procedures should be routinely
      performed prior to downstream analyses for the detection of bias in microarray
      studies.

PMID- 22133087
TI  - A many-body dissipative particle dynamics study of forced water-oil displacement
      in capillary.
AB  - The forced water-oil displacement in capillary is a model that has important
      applications such as the groundwater remediation and the oil recovery. Whereas it
      is difficult for experimental studies to observe the displacement process in a
      capillary at nanoscale, the computational simulation is a unique approach in this
      regard. In the present work, the many-body dissipative particle dynamics (MDPD)
      method is employed to simulate the process of water-oil displacement in capillary
      with external force applied by a piston. As the property of all interfaces
      involved in this system can be manipulated independently, the dynamic
      displacement process is studied systematically under various conditions of
      distinct wettability of water in capillary and miscibility between water and oil
      as well as of different external forces. By analyzing the dependence of the
      starting force on the properties of water/capillary and water/oil interfaces, we
      find that there exist two different modes of the water-oil displacement. In the
      case of stronger water-oil interaction, the water particles cannot displace those
      oil particles sticking to the capillary wall, leaving a low oil recovery
      efficiency. To minimize the residual oil content in capillary, enhancing the
      wettability of water and reducing the external force will be beneficial. This
      simulation study provides microscopic insights into the water-oil displacement
      process in capillary and guiding information for relevant applications.

PMID- 22133088
TI  - Vapour phase: a potential future use for essential oils as antimicrobials?
AB  - Essential oil (EO) vapours have been known for their antimicrobial properties
      since the 4th century B.C.; however, it was not until the early 1960s that
      research into the potential of these volatile oils was explored. More recently,
      the use of EOs such as tea tree, bergamot, lavender and eucalyptus in vapour form
      has been shown to have antimicrobial effects against both bacteria and fungi,
      with range of methods being developed for dispersal and efficacy testing. To
      date, many applications for EO vapours as antimicrobials have been identified
      including in the food and clinical arenas.

PMID- 22133090
TI  - Effect of persistent patent ductus arteriosus on mortality and morbidity in very
      low-birthweight infants.
AB  - AIM: Because New Caledonia is geographically isolated from the nearest cardiac
      surgical centre, surgical closure of ductus arteriosus is not performed in very
      low-birthweight (VLBW) infants who have a persistent patent ductus in spite of
      having undergone treatment with ibuprofen. This study aimed at investigating the
      possible effect of persistent patent ductus in VLBW infants. METHODS: The study
      included 177 VLBW infants born at 25-31 weeks of gestation from January 2006 to
      May 2011. Mortality and major morbidities were compared between infants with a
      persistent patent ductus (n = 33) and those without it (n = 104). Statistical
      associations between potential neonatal risk factors and significant morbidities
      were identified using multivariate regression analyses. RESULTS: Rates of
      mortality and major morbidities, including the rate of bronchopulmonary
      dysplasia, necrotizing enterocolitis, intraventricular haemorrhage grades I-II
      and III-IV, periventricular leucomalacia, late-onset infections and failure of
      hearing screening, were insignificantly higher in VLBW infants with a persistent
      patent ductus than in those without it. CONCLUSION: This study adds further
      evidence that persistent patent ductus arteriosus has no significant effect on
      mortality and morbidity in VLBW infants born at >=25 weeks' gestational age.

PMID- 22133091
TI  - Ameliorative effect of methanol extract of Rubia cordifolia in N
      nitrosodiethylamine-induced hepatocellular carcinoma.
AB  - CONTEXT: Rubia cordifolia Linn. (Rubiaceae) is a medicinal plant used in the
      ayurvedic system of medicine. It is also known as Indian Madder or Manjistha and
      is traditionally used as an antiinflammatory, antiseptic, and galactopurifier,
      but its anticancer propertis are yet not known. OBJECTIVE: The ameliorative
      effect of the Rubia cordifolia methanol extract on N-nitrosodiethylamine-induced
      experimental hepatocellular carcinogenesis in rats. MATERIALS AND METHODS:
      Changes in liver weight, serum markers of liver damage, hydroxyl radicals, lipid
      peroxidation, levels of enzymic and nonenzymic antioxidants; mitochondrial and
      respiratory chain enzymes were also investigated using various biochemical
      parameters and histopathological studies. Male albino rats of Wistar strain were
      divided into four groups for a study period of 3 months. Animals of group I and
      group IV served as control and drug control, respectively. Hepatocellular
      carcinoma was induced in animals of groups II and III with 0.02% N
      nitrosodiethylamine. RESULTS: Upon Rubia cordifolia methanol extract co-treatment
      (250, 500, and 750 mg/kg bodyweight) in group III alone levels of serum marker
      enzymes and antioxidants increased significantly in a dose-dependent manner. The
      levels of hydroxyl radicals and lipid peroxidation decreased. Mitochondrial
      enzymes and respiratory chain enzymes, which were decreased in N
      nitrosodiethylamine-induced rats, increased significantly in RC treated rats.
      Further histological analysis of liver confirmed the prevention of pathological
      changes caused by N-nitrosodiethylamine on Rubia cordifolia supplementation.
      DISCUSSION AND CONCLUSION: These findings demonstrate that Rubia cordifolia can
      be a source of potent antioxidants for treatment of diseases such as cancer.

PMID- 22133092
TI  - Kinase-kernel models: accurate in silico screening of 4 million compounds across
      the entire human kinome.
AB  - Reliable in silico prediction methods promise many advantages over experimental
      high-throughput screening (HTS): vastly lower time and cost, affinity magnitude
      estimates, no requirement for a physical sample, and a knowledge-driven
      exploration of chemical space. For the specific case of kinases, given several
      hundred experimental IC(50) training measurements, the empirically parametrized
      profile-quantitative structure-activity relationship (profile-QSAR) and surrogate
      AutoShim methods developed at Novartis can predict IC(50) with a reliability
      approaching experimental HTS. However, in the absence of training data,
      prediction is much harder. The most common a priori prediction method is docking,
      which suffers from many limitations: It requires a protein structure, is slow,
      and cannot predict affinity. (1)  Highly accurate profile-QSAR (2)  models have
      now been built for roughly 100 kinases covering most of the kinome. Analyzing
      correlations among neighboring kinases shows that near neighbors share a high
      degree of SAR similarity. The novel chemogenomic kinase-kernel method reported
      here predicts activity for new kinases as a weighted average of predicted
      activities from profile-QSAR models for nearby neighbor kinases. Three different
      factors for weighting the neighbors were evaluated: binding site sequence
      identity to the kinase neighbors, similarity of the training set for each
      neighbor model to the compound being predicted, and accuracy of each neighbor
      model. Binding site sequence identity was by far most important, followed by
      chemical similarity. Model quality had almost no relevance. The median R(2) =
      0.55 for kinase-kernel interpolations on 25% of the data of each set held out
      from method optimization for 51 kinase assays, approached the accuracy of median
      R(2) = 0.61 for the trained profile-QSAR predictions on the same held out 25%
      data of each set, far faster and far more accurate than docking. Validation on
      the full data sets from 18 additional kinase assays not part of method
      optimization studies also showed strong performance with median R(2) = 0.48.
      Genetic algorithm optimization of the binding site residues used to compute
      binding site sequence identity identified 16 privileged residues from a larger
      set of 46. These 16 are consistent with the kinase selectivity literature and
      structural biology, further supporting the scientific validity of the approach. A
      priori kinase-kernel predictions for 4 million compounds were interpolated from
      51 existing profile-QSAR models for the remaining >400 novel kinases, totaling 2
      billion activity predictions covering the entire kinome. The method has been
      successfully applied in two therapeutic projects to generate predictions and
      select compounds for activity testing.

PMID- 22133093
TI  - Fibrodysplasia ossificans progressiva: clinical and genetic aspects.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable
      disorder of connective tissue characterized by congenital malformations of the
      great toes and progressive heterotopic ossification that forms qualitatively
      normal bone in characteristic extraskeletal sites. The worldwide prevalence is
      approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic
      predilection to FOP. Children who have FOP appear normal at birth except for
      congenital malformations of the great toes. During the first decade of life,
      sporadic episodes of painful soft tissue swellings (flare-ups) occur which are
      often precipitated by soft tissue injury, intramuscular injections, viral
      infection, muscular stretching, falls or fatigue. These flare-ups transform
      skeletal muscles, tendons, ligaments, fascia, and aponeuroses into heterotopic
      bone, rendering movement impossible. Patients with atypical forms of FOP have
      been described. They either present with the classic features of FOP plus one or
      more atypical features [FOP plus], or present with major variations in one or
      both of the two classic defining features of FOP [FOP variants]. Classic FOP is
      caused by a recurrent activating mutation (617G>A; R206H) in the gene ACVR1/ALK2
      encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic
      protein (BMP) type I receptor. Atypical FOP patients also have heterozygous ACVR1
      missense mutations in conserved amino acids. The diagnosis of FOP is made by
      clinical evaluation. Confirmatory genetic testing is available. Differential
      diagnosis includes progressive osseous heteroplasia, osteosarcoma, lymphedema,
      soft tissue sarcoma, desmoid tumors, aggressive juvenile fibromatosis, and non
      hereditary (acquired) heterotopic ossification. Although most cases of FOP are
      sporadic (noninherited mutations), a small number of inherited FOP cases show
      germline transmission in an autosomal dominant pattern. At present, there is no
      definitive treatment, but a brief 4-day course of high-dose corticosteroids,
      started within the first 24 hours of a flare-up, may help reduce the intense
      inflammation and tissue edema seen in the early stages of the disease.
      Preventative management is based on prophylactic measures against falls,
      respiratory decline, and viral infections. The median lifespan is approximately
      40 years of age. Most patients are wheelchair-bound by the end of the second
      decade of life and commonly die of complications of thoracic insufficiency
      syndrome.

PMID- 22133094
TI  - Thermal conductivity of carbon nanotubes and graphene in epoxy nanofluids and
      nanocomposites.
AB  - We employed an easy and direct method to measure the thermal conductivity of
      epoxy in the liquid (nanofluid) and solid (nanocomposite) states using both
      rodlike and platelet-like carbon-based nanostructures. Comparing the experimental
      results with the theoretical model, an anomalous enhancement was obtained with
      multiwall carbon nanotubes, probably due to their layered structure and lowest
      surface resistance. Puzzling results for functionalized graphene sheet
      nanocomposites suggest that phonon coupling of the vibrational modes of the
      graphene and of the polymeric matrix plays a dominant role on the thermal
      conductivities of the liquid and solid states.PACS: 74.25.fc; 81.05.Qk; 81.07.Pr.

PMID- 22133095
TI  - Reproductive conflicts in polyandrous and polygynous ant Formica sanguinea.
AB  - The occurrence of multiple reproductives within an ant colony changes the balance
      between indirect fitness benefits and reproductive competition. We test whether
      the number of matings by an ant queen (polyandry) correlates negatively with the
      number of reproductive queens in the colony (polygyny), whether the patrilines
      and matrilines differ in their contribution to the sexual and worker progeny and
      whether there is an overall reproductive skew. For these aims, we genotyped both
      worker and sexual offspring from colonies of the ant Formica sanguinea in three
      populations. Most colonies were monogynous, but eight (11%) were polygynous with
      closely related queens. Most queens in the monogynous colonies (86%) had mated
      with multiple males. The effective paternity was lower than the actual number of
      mates, and the paternity skew was significant. Furthermore, in some monogynous
      colonies, the patrilines were differently represented in the worker pupae and
      sexual pupae produced at the same time. Likewise, the matrilines in polygynous
      colonies were differently present in worker pupae and male offspring. The
      effective number of matings by a queen was significantly lower in polygynous
      colonies (mean m(e)  = 1.68) than in monogynous colonies (means 2.06-2.61). The
      results give support to the hypotheses that polyandry and polygyny are
      alternative breeding strategies and that reproductive competition can lead to
      different representation of patrilines and matrilines among the sexual and worker
      broods.

PMID- 22133096
TI  - Effects of an oral insulin nanoparticle administration on hepatic glucose
      metabolism assessed by 13C and 2H isotopomer analysis.
AB  - The purpose of this study was to evaluate hepatic glucose metabolism of diabetic
      induced rats after a daily oral load of insulin nanoparticles over 2 weeks. After
      the 2-week treatment, an oral glucose tolerance test was performed with [U-13C]
      glucose and 2H2O. Plasma glucose 2H and 13C enrichments were quantified and the
      contribution of glycogenolysis and gluconeogenesis to overall glucose production
      were estimated. Animals with the insulin nanoparticles displayed the lowest
      glycemia before the oral glucose tolerance test. In all animals, 75% of the total
      glucose production was from gluconeogenesis and glycogen synthesis was only
      detected in some animals. Gluconeogenic pathway was an active contributor to
      hepatic glucose production and the treatment with oral delivered insulin
      nanoparticles did not alter this contribution, suggesting that under this
      treatment, protocol hepatic glucose metabolism is not the most relevant target of
      insulin action but instead a more generalised effect in peripheral tissues.

PMID- 22133097
TI  - Green polymer chemistry: living dithiol polymerization via cyclic intermediates.
AB  - This paper reports the synthesis and characterization of disulfide polymers
      obtained by oxidation of 2-[2-(2-sulfanylethoxy)ethoxy]ethanethiol (DODT) using a
      benign, synergistic system comprised of air, dilute hydrogen peroxide and
      triethylamine as a catalyst that can be recycled. The dn/dc value of the polymer
      in THF was determined to obtain absolute molecular weight measurements. High
      molecular weight disulfide polymers (up to M(n) = 250000 g/mol) with
      polydispersity indices as low as M(w)/M(n) = 1.15 were obtained. Thermal analysis
      by DSC and TGA demonstrated that the rubbery polymers had a T(g) of -50  degrees
      C and began to degrade at 250  degrees C. Dithiothreitol reduced the polymers
      back to the original monomeric units in 33 h. MALDI-ToF showed the involvement of
      oligodisulfide rings (2-14 mers) in the polymerization that displayed the
      characteristics of a living/controlled polymerization; poly(DODT) was readily
      chain extended with 1,2-ethanedithiol. The chain extension indicates a class of
      living polymerization which is governed by radical recombination.

PMID- 22133098
TI  - Individual vitamin B6 contents in selected Japanese sushi toppings.
AB  - The contents of six natural vitamin B(6) forms in popular Japanese sushi toppings
      were determined by a 4-pyridoxolactone-conversion HPLC method. The half-baked
      bonito exhibited the highest total vitamin B(6) content and the northern shrimp
      sashimi the lowest. Pyridoxal 5'-phosphate plus pyridoxal was predominant in nine
      samples, and pyridoxamine 5'-phosphate plus pyridoxamine in two other samples.
      Pyridoxine 5'-phosphate plus pyridoxine was minor. The raw meats (sashimi) of
      fatty seawater fishes contain a lot of pyridoxal 5'-phosphate and/or pyridoxamine
      5'-phosphate. Five portions of sushi with 20 g of fatty seawater sashimi toppings
      would supply with vitamin B(6) recommended by the Japanese Recommended Daily
      Allowance.

PMID- 22133099
TI  - Percutaneous ultrasonography-guided permanent iodine-125 implantation as salvage
      therapy for recurrent head and neck carcimonas.
AB  - Twenty-nine (29) patients with recurrent head and neck carcinomas underwent
      (125)I seed permanent implantation under ultrasonography guidance and the
      feasibility and efficacy of (125)I seed implantation were assessed. The postplan
      evaluation showed that the actuarial D90 of (125)I seeds ranged from 90 to 160 Gy
      (median, 130 Gy). The activity of each (125)I seed ranged from 0.35 to 0.8 mCi
      (median, 0.6 mCi). The total number of sources implanted ranged from 3 to 61
      (median, 22). The follow-up ranged from 3 to 40 months (median, 8 months). The 1
      , 2-, and 3-year local control rates were 53.1%, 34.8%, and 17.4%, respectively,
      with a median local control of 16 months (95% confidence interval, 5.8-26.1). The
      1-, 2-, and 3- year survival rates were 54.1%, 27.5%, and 27.5%, respectively
      (median, 13 months; 95% confidence interval, 6.0-19.9). Of the 25 patients, 5
      (17.2%) died of local recurrence and 7 (24.1%) died of metastases; 2 patients
      showed recurrences at 3 and 8 months after seed implantation and subsequently
      died of pneumonia. One (1) patient died of heart disease. One (1) developed
      ulceration with tumor progression. Blood vessel damage and neuropathy were not
      observed. Percutaneous ultrasound-guided (125)I seed implantation is a feasible,
      safe salvage for patients with recurrent carcinomas of the head and neck.

PMID- 22133100
TI  - Hydrangenone, a new isoprenoid with an unprecedented skeleton from Salvia
      hydrangea.
AB  - Hydrangenone, a new heptacyclic isoprenoid with a 6/7/6/5/5 membered carbon ring
      skeleton, was isolated from the aerial parts of Salvia hydrangea. The structure
      was established by extensive NMR spectroscopic methods. The relative and absolute
      configuration of 1 was assigned by NOESY and X-ray crystallographic analysis and
      by comparison of experimental and calculated electronic circular dichroism (ECD)
      spectra. Compound 1 showed in vitro antiplasmodial activity, with an IC(50) value
      of 1.4 MUM against P. falciparum. A plausible biosynthetic pathway of 1 was also
      proposed.

PMID- 22133101
TI  - Determination of cell death modes using circulating biomarkers.

PMID- 22133102
TI  - Determination of trace nickel in hydrogenated cottonseed oil by electrothermal
      atomic absorption spectrometry after microwave-assisted digestion.
AB  - Microwave digestion of hydrogenated cottonseed oil prior to trace nickel
      determination by electrothermal atomic absorption spectrometry (ETAAS) is
      proposed here for the first time. Currently, the methods outlined in U.S.
      Pharmacopeia 28 (USP28) or British Pharmacopeia (BP2003) are recommended as the
      official methods for analyzing nickel in hydrogenated cottonseed oil. With these
      methods the samples may be pre-treated by a silica or a platinum crucible.
      However, the samples were easily tarnished during sample pretreatment when using
      a silica crucible. In contrast, when using a platinum crucible, hydrogenated
      cottonseed oil acting as a reducing material may react with the platinum and
      destroy the crucible. The proposed microwave-assisted digestion avoided
      tarnishing of sample in the process of sample pretreatment and also reduced the
      cycle of analysis. The programs of microwave digestion and the parameters of
      ETAAS were optimized. The accuracy of the proposed method was investigated by
      analyzing real samples. The results were compared with the ones by pressurized
      PTFE-bomb acid digestion and ones obtained by the U.S. Pharmacopeia 28 (USP28)
      method. The new method involves a relatively rapid matrix destruction technique
      compared with other present methods for the quantification of metals in oil.

PMID- 22133103
TI  - Strained cyclophane macrocycles: impact of progressive ring size reduction on
      synthesis and structure.
AB  - The synthesis, X-ray crystal structures, and calculated strain energies are
      reported for a homologous series of 11- to 14-membered drug-like cyclophane
      macrocycles, representing an unusual region of chemical space that can be
      difficult to access synthetically. The ratio of macrocycle to dimer, generated
      via a copper catalyzed azide-alkyne cycloaddition macrocyclization in flow at
      elevated temperature, could be rationalized in terms of the strain energy in the
      macrocyclic product. The progressive increase in strain resulting from reduction
      in macrocycle ring size, or the introduction of additional conformational
      constraints, results in marked deviations from typical geometries. These strained
      cyclophane macrocyclic systems provide access to spatial orientations of
      functionality that would not be readily available in unstrained or acyclic
      analogs. The most strained system prepared represents the first report of an 11
      membered cyclophane containing a 1,4-disubstituted 1,2,3-triazole ring and
      establishes a limit to the ring strain that can be generated using this
      macrocycle synthesis methodology.

PMID- 22133104
TI  - Sustaining critical social services during extended regional power blackouts.
AB  - Despite continuing efforts to make the electric power system robust, some risk
      remains of widespread and extended power outages due to extreme weather or acts
      of terrorism. One way to alleviate the most serious effects of a prolonged
      blackout is to find local means to secure the continued provision of critical
      social services upon which the health and safety of society depend. This article
      outlines and estimates the incremental cost of a strategy that uses small
      distributed generation, distribution automation, and smart meters to keep a set
      of critical social services operational during a prolonged power outage that
      lasts for days or weeks and extends over hundreds of kilometers.

PMID- 22133105
TI  - Cysteamine-based functionalization of InAs surfaces: revealing the critical role
      of oxide interactions in biasing attachment.
AB  - Attaching functional molecules such as thiols and proteins to semiconductor
      surfaces is increasingly exploited in functional devices such as sensors. Despite
      extensive research to understand this interface and demonstrate a robust protocol
      for attachment, the bonding chemistry of thiolates to III-V surfaces has been
      under great debate in the literature. This study provides a comprehensive
      chemical model for the attachment of thiols to InAs, an increasingly device
      relevant III-V semiconductor, using cysteamine as a model molecule. We examine
      the attachment of cysteamine to InAs via the thiol group using X-ray
      photoelectron spectroscopy and spectroscopic ellipsometry and confirm that
      thiolate bonding to the substrate occurs preferentially to As sites over In sites
      as a limit. These experiments explore the interplay of the native oxide chemical
      properties, the cysteamine concentration, and the evolving InAs surface chemistry
      with functionalization. The thiol-InAs interaction can be framed as a general
      acid-base reaction, where the nucleophilic and/or electrophilic attack of the
      surface (i.e., binding to In sites and/or As sites) depends on the acidity of the
      thiol. The roles of the initial oxide composition, the solvent of the
      functionalizing solution, and the cysteamine as a limiting reagent in fully
      displacing the oxide and creating In-S and As-S bonds are highlighted.

PMID- 22133106
TI  - From solid state to solution: advancing chemistry of Bi-Bi and Bi-Rh paddlewheel
      carboxylates.
AB  - The first successful high-yield solution synthesis of homobimetallic
      Bi(2)(O(2)CCF(3))(4) (1), as well as heterobimetallic BiRh(O(2)CCF(3))(4) (2) and
      BiRh(O(2)CCF(2)CF(3))(4) (3), complexes is reported. It is based on one-pot
      reduction reactions starting from Bi(III) and Rh(II) carboxylates and using Bi
      metal as a reducing agent. The presence of small amounts of diphenyl ether was
      found to facilitate this reaction, most probably because of its good solubilizing
      and pi-stabilizing abilities. The latter is illustrated by the isolation and
      structural characterization of a pi-adduct of 1 with diphenyl ether,
      [Bi(2)(O(2)CCF(3))(4).1/2Ph(2)O]. Importantly, the new approach expands to
      solution the chemistry of Bi(II) that was previously limited to the solid state
      only. The solution procedure developed for the preparation of heterometallic
      BiRh(O(2)CCF(3))(4) is now one step shorter and gives the product in excellent
      yield compared with the previously reported method based on sublimation
      deposition technique. It is also performed on a greater scale (~10-20 times) and
      makes further scale-up feasible, if needed. Moreover, it eliminates the isolation
      of the hard-to-handle unsolvated Bi(II) trifluoroacetate used earlier as a
      starting material. A new polymorph of BiRh(O(2)CCF(3))(4) (2) was crystallized
      from solution in this work. The solution approach was also applied to the
      synthesis of a new heterobimetallic carboxylate with perfluorinated propionate
      ligands, BiRh(O(2)CCF(2)CF(3))(4) (3). All products are fully characterized by
      spectroscopic and single crystal X-ray diffraction methods. Complexes 2 and 3
      exhibit similar solid state structures based on heterobimetallic paddlewheel
      units forming infinite 1D chains through intermolecular Rh...O interactions.

PMID- 22133107
TI  - The effects of Feijoa sellowiana fruits on the antioxidant defense system, lipid
      peroxidation, and tissue morphology in rats.
AB  - CONTEXT: The fruits of Feijoa sellowiana Berg. (Myrtaceae) have been used to
      treat goiter in traditional Turkish medicine. OBJECTIVE: To evaluate the in vivo
      antioxidant activities of different polarities of the fruit extracts in blood and
      tissue (liver, kidney, brain, and heart) antioxidant defense systems in standard
      pellet diet and in high fat diet consumed, male rats were assessed. MATERIALS AND
      METHODS: The extracts (methanol, n-hexane, chloroform, ethyl acetate, n-butanol,
      and aqueous) were administered orally to male rats at 50 mg/kg doses daily for 4
      weeks. The blood and tissue malondialdehyde (MDA), reduced glutathione (GSH)
      levels, plasma nitrate (NO(x)) level, total triiodothyronine (T3), thyroxine,
      cholesterol, triglyceride, protein, and glucose levels were determined, and
      erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities; plasma
      antioxidant activity (AOA) were experimentally studied. RESULTS: Blood MDA level
      (7.81 +/- 0.4) was significantly decreased; GSH level (29.65 +/- 1.21) and AOA
      (1.52 +/- 0.08) were increased in ethyl acetate extract as compared with control
      and the other extracts. In addition, all the extracts decreased MDA levels and
      increased GSH levels (except brain tissue homogenate) in the tissue homogenates.
      Erythrocyte SOD and CAT activity levels were unchanged in F. sellowiana extracts.
      However, the extracts had no effect on plasma NO(x). In the histopathological
      examinations, any changes or damage in the vital organs were seen in animals.
      CONCLUSION: The experimental data demonstrated that F. sellowiana extracts
      displayed remarkable antioxidant activity and decreased lipid peroxidation in
      rats; furthermore, no histopathological changes or damage have been observed in
      the vital organs of rats.

PMID- 22133108
TI  - Prevalence of overweight and obesity in Danish preschool children over a 10-year
      period: a study of two birth cohorts in general practice.
AB  - AIM: To determine change in the prevalence of overweight and obesity in preschool
      children, over a 10-year period and to identify possible predictors of overweight
      in 5-year-old children. METHODS: Anthropometric data from birth and routine child
      health examinations at 3 and 5 years of age performed in general practice were
      collected in 5580 children from two Funen birth cohorts (1992 and 2001,
      respectively) representing 48% of the total population at similar age. The
      prevalence of overweight and obesity was classified using the International
      Obesity Task Force definitions. RESULTS: In a Danish representative survey of
      preschool children, the average body mass index (BMI) and prevalence of
      overweight and obesity did not vary significantly during the 10-year period. No
      significant changes in mean birth weight were registered and mean BMI in the
      group of obese children did not increase. Overweight or obesity at 5 years was
      strongly associated with overweight and obesity at 3 years and with birth weight
      and gender. CONCLUSION: The prevalence of overweight and obesity was observed to
      be stable over a decade in Danish preschool children without changes in mean BMI
      in the group of obese children. A strong association between overweight and
      obesity at 3 and at 5 years of age was detected.

PMID- 22133109
TI  - Femtosecond multiphoton ionization of pyrrole.
AB  - The photoionization dynamics of pyrrole are investigated by using a photoelectron
      imaging method and a tunable femtosecond laser. Two-photon nonresonant ionization
      experiments in the wavelength range from 261 to 298 nm indicate that the cation
      and neutral ground states have similar structures. The main vibrational
      excitation in the cation ground state is the v(8) mode. Two-photon absorption at
      406 nm projects neutral pyrrole into a mixed state comprising the 1B(2) valence
      and 3p Rydberg states. Ionization from this mixed state mainly results in the
      overtone excitation of vibrational mode v(8) and v(9) of the cation state. In the
      wavelength range from 336 to 364 nm, a mixed state comprising the 3d/4s Rydberg
      and the 4A(1) valence states are populated by the absorption of two photons
      through vibronic coupling. The partition ratio among these states varies with the
      excitation wavelength, resulting in dramatic changes in both kinetic energy
      distributions and angular distributions. As the laser wavelength becomes shorter,
      from 336 to 314 nm, higher excited states, 3B(2), 5A(1), 6A(1), 7B(1) and 4B(2),
      can be populated. Photoelectron angular distributions provide supplementary
      verification of assignments. Our experiments indicate that femtosecond
      multiphoton ionization and photoelectron imaging methods are powerful tools for
      investigating short-lived intermediated excited states, which cannot be detected
      in nanosecond experiments.

PMID- 22133110
TI  - Corrigenda.
AB  - Abstract   In Table I of the paper Growth hormone responsive dermatosis in three
      dogs (New Zealand Veterinary Journal 41, 19.5-9, 1993), the units for the
      following biochemical tests are given in MUmol/l, whereas the correct units are
      mmol/l: blood urea, glucose, cholesterol, calcium, inorganic phosphate, sodium
      and potassium.

PMID- 22133111
TI  - Transcriptomic analysis of follicular cells provides information on the
      chromosomal status and competence of unfertilized oocytes.

PMID- 22133112
TI  - Surface plasmon resonance: recent progress toward the development of portable
      real-time blood diagnostics.

PMID- 22133113
TI  - Hybrid optoelectric techniques for molecular diagnostics.

PMID- 22133115
TI  - Highlights from the 7th European meeting on molecular diagnostics.
AB  - This report presents the highlights of the 7th European Meeting on Molecular
      Diagnostics held in Scheveningen, The Hague, The Netherlands, 12-14 October 2011.
      The areas covered included molecular diagnostics applications in medical
      microbiology, virology, pathology, hemato-oncology, clinical genetics and
      forensics. Novel real-time amplification approaches, novel diagnostic
      applications and new technologies, such as next-generation sequencing, PCR
      electrospray-ionization TOF mass spectrometry and techniques based on the
      detection of proteins or other molecules, were discussed. Furthermore, diagnostic
      companies presented their future visions for molecular diagnostics in human
      healthcare.

PMID- 22133116
TI  - TB diagnostics in India: creating an ecosystem for innovation.
AB  - The 'TB diagnostics in India: from importation and imitation to innovation'
      conference was held in Bangalore, India, on 25-26 August 2011, and was organized
      by the St. John's Research Institute, Bangalore, with the support of several
      partners. This unique conference brought together, for the first time, over 220
      representatives from industry, government, donors, academia, civil society and
      the media to discuss what it takes to innovate in tuberculosis (TB) diagnostics
      in India. The goal was to engage these stakeholders to stimulate interest and
      investments in TB innovations. The conference was successful in engaging
      stakeholders and understanding the challenge of TB innovations from diverse
      perspectives. Coordination between stakeholders and innovations in delivery
      systems, partnerships, funding, regulatory and communication mechanisms are among
      the key challenges ahead.

PMID- 22133117
TI  - How novel molecular diagnostic technologies and biomarkers are revolutionizing
      genetic testing and patient care.
AB  - Technological applications and novel biomarkers in the field of molecular
      diagnostics have never been evolving at a more rapid pace. These novel
      applications have the promise to change the face of clinical care as we move into
      the era of personalized medicine. While some of these technologies and biomarkers
      have been adopted by some clinical laboratories, most laboratories face a steep
      learning curve in bringing these dramatically new and different molecular
      diagnostic applications on board. Furthermore, interpreting the vast amounts and
      new types of data produced by these novel applications brings forth challenges
      for laboratorians and clinicians alike. In this article, we discuss how some of
      these emerging novel molecular diagnostic technologies and analytes, such as next
      generation sequencing, chromosomal microarray, microRNAs and circulating fetal
      nucleic acids are revolutionizing patient care and personalized medicine.

PMID- 22133118
TI  - Methylation-sensitive high-resolution melting in the context of legislative
      requirements for validation of analytical procedures for diagnostic applications.
AB  - Temperature gradient was first used to identify the methylation status of the DNA
      sequence over 10 years ago; however, the initially published protocol was shown
      to have poor analytical sensitivity. Recent developments in the field of DNA
      melting technologies, combined with the identification of procedures to overcome
      the sensitivity issues in the PCR-based methylation detection applications, led
      to the development of the methylation-sensitive high-resolution melting (MS-HRM)
      protocol. This protocol allows for highly sensitive detection of methylation
      levels in a labor- and cost-efficient fashion. Moreover, it enables investigation
      of methylation status of imprinted loci as well as identification of
      heterogeneous methylation. The MS-HRM technology is being increasingly applied in
      research laboratories and has a potential for future application in diagnostic
      settings. The focus of this article is to describe the development of the HRM
      technology for methylation analyses and evaluate the diagnostic applicability of
      the MS-HRM technology.

PMID- 22133119
TI  - Luminescent nanoparticles and their use for in vitro and in vivo diagnostics.
AB  - Fluorescence spectroscopy has been shown to be a useful tool for a broad variety
      of biological and medical applications. Many of the analytical methods, as used
      for tumor marker and gene mutation detection, recognition of pathogens or
      monitoring of cell-related processes, are based on the labeling of the
      investigating object with luminescent nanoparticles. Owing to their size, which
      is comparable to that of biomolecules, and to their extraordinary optical
      properties, luminescent nanoparticles could well improve the sensitivity and
      flexibility of current detection techniques. This article provides a general
      overview of the synthesis, properties and application of luminescent
      semiconductor, metal and inorganic nanoparticles for in vitro and in vivo
      diagnostics, also reflecting the aspect of biocompatibility.

PMID- 22133120
TI  - Antinuclear antibodies as ancillary markers in primary biliary cirrhosis.
AB  - Antimitochondrial antibodies are the serological hallmark of primary biliary
      cirrhosis (PBC). Besides antimitochondrial antibodies, the autoantibody profile
      of PBC includes antinuclear antibodies (ANA) which are detectable by indirect
      immunofluorescence in up to 50% of PBC patients. Two immunofluorescence patterns
      are considered 'PBC-specific': the multiple nuclear dots and rim-like/membranous
      patterns. The target antigens of the multiple nuclear dots pattern have been
      identified as Sp100 and promyelocytic leukemia protein, whereas the rim
      like/membranous pattern is given by autoantibodies recognizing multiple proteins
      such as gp210, nucleoporin p62 and the lamin B receptor. Other ANA, especially
      those already known in the rheumatological setting, such as anticentromere, anti
      SSA/Ro and anti-dsDNA antibodies, can be frequently found in PBC, often
      coexisting in the same patient. In this article, we will report on recent
      progress in the antigenic characterization of ANA in PBC, their detection with
      both traditional assays and Western blot/ELISA with molecularly defined nuclear
      antigens, and we will discuss their clinical significance.

PMID- 22133121
TI  - DNA methylation testing and marker validation using PCR: diagnostic applications.
AB  - DNA methylation provides a fundamental epigenetic mechanism to establish and
      promote cell-specific gene-expression patterns, which are inherited by subsequent
      cell generations. Thus, the epigenome determines the differentiation into a cell
      lineage but can also program cells to become abnormal or malignant. In humans,
      different germline and somatic diseases have been linked to faulty DNA
      methylation. In this article, we will discuss the available PCR-based
      technologies to assess differences in DNA methylation levels mainly affecting 5
      methylcytosine in the CpG dinucleotide context in hereditary syndromal and
      somatic pathological conditions. We will discuss some of the current diagnostic
      applications and provide an outlook on how DNA methylation-based biomarkers might
      provide novel tools for diagnosis, prognosis or patient stratification for
      diseases such as cancer.

PMID- 22133122
TI  - Molecular changes in smoking-related lung cancer.
AB  - To elucidate the effect of cigarette smoke on developing lung cancer among
      individuals, numerous genetic and epigenetic factors related to cigarette smoke
      induced lung cancers have been widely investigated and a various genes, loci and
      pathways have been identified as candidates to date. However, the importance of
      these molecular alterations in the initiation and progression of lung cancer
      still remains imprecise and different molecules altered in lung cancer are being
      used for stratification of patients for targeted therapy. There are a number of
      molecular pathways involved in the development of lung cancer, and environmental
      factors related to these alterations are still unclear. Furthermore, various
      genetic alterations determined by candidate gene approach have not been re
      evaluated for their functional significance together with epigenetic alterations
      in the same population. Accumulated evidence suggested that lung cancer in ever
      smokers and never smokers follow distinct molecular pathways and may therefore
      respond to distinct therapy. Therefore, additional studies will be essential to
      re-evaluate the individual risk of developing lung cancer based on the
      combination of genetic and epigenetic alterations and to set up a guideline to
      assess the individual risk for lung cancer and for its prevention.

PMID- 22133125
TI  - Revealing the missing expressed genes beyond the human reference genome by RNA
      Seq.
AB  - BACKGROUND: The complete and accurate human reference genome is important for
      functional genomics researches. Therefore, the incomplete reference genome and
      individual specific sequences have significant effects on various studies.
      RESULTS: we used two RNA-Seq datasets from human brain tissues and 10 mixed cell
      lines to investigate the completeness of human reference genome. First, we
      demonstrated that in previously identified ~5 Mb Asian and ~5 Mb African novel
      sequences that are absent from the human reference genome of NCBI build 36, ~211
      kb and ~201 kb of them could be transcribed, respectively. Our results suggest
      that many of those transcribed regions are not specific to Asian and African, but
      also present in Caucasian. Then, we found that the expressions of 104 RefSeq
      genes that are unalignable to NCBI build 37 in brain and cell lines are higher
      than 0.1 RPKM. 55 of them are conserved across human, chimpanzee and macaque,
      suggesting that there are still a significant number of functional human genes
      absent from the human reference genome. Moreover, we identified hundreds of novel
      transcript contigs that cannot be aligned to NCBI build 37, RefSeq genes and EST
      sequences. Some of those novel transcript contigs are also conserved among human,
      chimpanzee and macaque. By positioning those contigs onto the human genome, we
      identified several large deletions in the reference genome. Several conserved
      novel transcript contigs were further validated by RT-PCR. CONCLUSION: Our
      findings demonstrate that a significant number of genes are still absent from the
      incomplete human reference genome, highlighting the importance of further
      refining the human reference genome and curating those missing genes. Our study
      also shows the importance of de novo transcriptome assembly. The comparative
      approach between reference genome and other related human genomes based on the
      transcriptome provides an alternative way to refine the human reference genome.

PMID- 22133126
TI  - Pit-bull reviewing, the pursuit of perfection and the victims of success.

PMID- 22133128
TI  - Is it time to monitor flow bias during mechanical ventilation?

PMID- 22133127
TI  - Standard procedures for adults in accredited sleep medicine centres in Europe.
AB  - The present paper describes standardized procedures within clinical sleep
      medicine. As such, it is a continuation of the previously published European
      guidelines for the accreditation of sleep medicine centres and European
      guidelines for the certification of professionals in sleep medicine, aimed at
      creating standards of practice in European sleep medicine. It is also part of a
      broader action plan of the European Sleep Research Society, including the process
      of accreditation of sleep medicine centres and certification of sleep medicine
      experts, as well as publishing the Catalogue of Knowledge and Skills for sleep
      medicine experts (physicians, non-medical health care providers, nurses and
      technologists), which will be a basis for the development of relevant educational
      curricula. In the current paper, the standard operational procedures sleep
      medicine centres regarding the diagnostic and therapeutic management of patients
      evaluated at sleep medicine centres, accredited according to the European
      Guidelines, are based primarily on prevailing evidence-based medicine principles.
      In addition, parts of the standard operational procedures are based on a
      formalized consensus procedure applied by a group of Sleep Medicine Experts from
      the European National Sleep Societies. The final recommendations for standard
      operational procedures are categorized either as 'standard practice', 'procedure
      that could be useful', 'procedure that is not useful' or 'procedure with
      insufficient information available'. Standard operational procedures described
      here include both subjective and objective testing, as well as recommendations
      for follow-up visits and for ensuring patients' safety in sleep medicine. The
      overall goal of the actual standard operational procedures is to further develop
      excellence in the practice and quality assurance of sleep medicine in Europe.

PMID- 22133129
TI  - High-flow nasal cannula for neonatal respiratory distress: is it enough?

PMID- 22133130
TI  - Oxygen: the kiss of life.

PMID- 22133131
TI  - 2015 and beyond: usable and unbiased data.

PMID- 22133132
TI  - Clinical and hemodynamic effects of renin-angiotensin system blockade in cardiac
      transplant recipients.
AB  - Chronic kidney disease continues to be a major limiting factor for long-term
      survival of heart transplant recipients. Little is known about the early use of
      renin-angiotensin system (RAS) blocking agents and their impact on renal function
      and hemodynamics in heart transplant recipients. In this cohort study all
      eligible recipients of orthotopic heart transplants at the UTAH cardiac
      transplantation program from 2001 through 2007 were divided into 2 groups
      patients who were started on angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers within the first 4 weeks of transplantation and
      continued on these for >=4 weeks during the first 3 months (RAS blockade group, n
      = 75) and those who were not (non-RAS blockade group, n = 52). All patients were
      followed for 1 year after transplantation. There were no significant differences
      at baseline between the 2 groups. Estimated glomerular filtration rate at 12
      months was significantly higher in the RAS blockade group compared to the non-RAS
      blockade group (mean +/- SD, 56.3 +/- 22.4 vs 47.3 +/- 18.1 ml/min/1.73 m(2), p =
      0.036). At 12 months pulmonary artery systolic pressure was significantly lower
      in the RAS blockade group compared to the non-RAS blockade group (30.2 +/- 7.4 vs
      32.9 +/- 9.3 mm Hg, p = 0.023). Left ventricular ejection fraction and pulmonary
      capillary wedge pressure were similar between the 2 groups. In conclusion, early
      RAS blockade after heart transplantation is safe, well tolerated, and associated
      with better renal function and hemodynamic profile at 1 year after
      transplantation.

PMID- 22133133
TI  - Aspirin 50 versus 100 mg: a case of wrong dosing.

PMID- 22133134
TI  - What homozygous familial hypercholesterolemia produces and the will to withstand
      its complications.

PMID- 22133135
TI  - Early repolarization on electrocardiogram: benign or not?

PMID- 22133136
TI  - Athlete's heart or hypertrophic cardiomyopathy: the dilemma is still there.

PMID- 22133137
TI  - Ventricular noncompaction.

PMID- 22133138
TI  - To err is human, to monitor divine: environmental adaptations reduce everyday
      errors but do not improve monitoring.
AB  - The current study aimed to address error monitoring impairments in dementia using
      an intervention for execution deficits. Thirty-eight participants completed the
      Naturalistic Action Test (NAT) under two conditions: Standard and User-Centered.
      The Standard NAT followed the manual procedures; in the User-Centered NAT,
      objects were arranged sequentially, and distractor items were separated from
      target objects. While participants committed fewer errors in the User-Centered
      condition, there was no difference in the proportion of errors detected. However,
      the neuropsychological processes associated with monitoring differed across
      conditions. The results have implications for a neuropsychological model of error
      monitoring in dementia.

PMID- 22133139
TI  - Age-related slowing in cognitive processing speed is associated with myelin
      integrity in a very healthy elderly sample.
AB  - Performance on measures of cognitive processing speed (CPS) slows with age, but
      the biological basis associated with this cognitive phenomenon remains
      incompletely understood. We assessed the hypothesis that the age-related slowing
      in CPS is associated with myelin breakdown in late-myelinating regions in a very
      healthy elderly population. An in vivo magnetic resonance imaging (MRI) biomarker
      of myelin integrity was obtained from the prefrontal lobe white matter and the
      genu of the corpus callosum for 152 healthy elderly adults. These regions
      myelinate later in brain development and are more vulnerable to breakdown due to
      the effects of normal aging. To evaluate regional specificity, we also assessed
      the splenium of the corpus callosum as a comparison region, which myelinates
      early in development and primarily contains axons involved in visual processing.
      The measure of myelin integrity was significantly correlated with CPS in highly
      vulnerable late-myelinating regions but not in the splenium. These results have
      implications for the neurobiology of the cognitive changes associated with brain
      aging.

PMID- 22133145
TI  - Updated bioavailability and 48 h excretion profile of flavan-3-ols from green tea
      in humans.
AB  - Green tea is a popular beverage, prepared with infusion of unfermented dried
      leaves of Camellia sinensis, and is one of the most relevant sources of
      polyphenolic compounds in the human diet. This study reports green tea flavan-3
      ol absorption, metabolism and complete urinary excretion up to 48 h in 20 healthy
      volunteers. Urinary and tea samples were analysed by high-performance liquid
      chromatography coupled with tandem mass spectrometry. Green tea contained
      monomeric flavan-3-ols and proanthocyanidins with a total polyphenol content of
      728 MUmol. A total of 41 metabolites were identified in urines, all present in
      conjugated forms. Among these, six colonic metabolites of green tea flavan-3-ols
      were identified for the first time after green tea consumption in humans. The
      average 48 h bioavailability was close to 62%, major contributors being microbial
      metabolites. Some volunteer showed a 100% absorption/excretion, whereas some
      others were unable to efficiently absorb/excrete this class of flavonoids. This
      suggests that colonic ring fission metabolism could be relevant in the putative
      bioactivity of green tea polyphenols.

PMID- 22133144
TI  - Dynamic proteomic profiling of a unicellular cyanobacterium Cyanothece ATCC51142
      across light-dark diurnal cycles.
AB  - BACKGROUND: Unicellular cyanobacteria of the genus Cyanothece are recognized for
      their ability to execute nitrogen (N2)-fixation in the dark and photosynthesis in
      the light. An understanding of these mechanistic processes in an integrated
      systems context should provide insights into how Cyanothece might be optimized
      for specialized environments and/or industrial purposes. Systems-wide dynamic
      proteomic profiling with mass spectrometry (MS) analysis should reveal
      fundamental insights into the control and regulation of these functions. RESULTS:
      To expand upon the current knowledge of protein expression patterns in Cyanothece
      ATCC51142, we performed quantitative proteomic analysis using partial
      ("unsaturated") metabolic labeling and high mass accuracy LC-MS analysis. This
      dynamic proteomic profiling identified 721 actively synthesized proteins with
      significant temporal changes in expression throughout the light-dark cycles, of
      which 425 proteins matched with previously characterized cycling transcripts. The
      remaining 296 proteins contained a cluster of proteins uniquely involved in DNA
      replication and repair, protein degradation, tRNA synthesis and modification,
      transport and binding, and regulatory functions. Functional classification of
      labeled proteins suggested that proteins involved in respiration and glycogen
      metabolism showed increased expression in the dark cycle together with
      nitrogenase, suggesting that N2-fixation is mediated by higher respiration and
      glycogen metabolism. Results indicated that Cyanothece ATCC51142 might utilize
      alternative pathways for carbon (C) and nitrogen (N) acquisition, particularly,
      aspartic acid and glutamate as substrates of C and N, respectively. Utilization
      of phosphoketolase (PHK) pathway for the conversion of xylulose-5P to pyruvate
      and acetyl-P likely constitutes an alternative strategy to compensate higher ATP
      and NADPH demand. CONCLUSION: This study provides a deeper systems level insight
      into how Cyanothece ATCC51142 modulates cellular functions to accommodate
      photosynthesis and N2-fixation within the single cell.

PMID- 22133146
TI  - Biomarkers of breast cancer apoptosis induced by chemotherapy and TRAIL.
AB  - Treatment of breast cancer is complex and challenging due to the heterogeneity of
      the disease. To avoid significant toxicity and adverse side-effects of
      chemotherapy in patients who respond poorly, biomarkers predicting therapeutic
      response are essential. This study has utilized a proteomic approach integrating
      2D-DIGE, LC-MS/MS, and bioinformatics to analyze the proteome of breast cancer
      (ZR-75-1 and MDA-MB-231) and breast epithelial (MCF-10A) cell lines induced to
      undergo apoptosis using a combination of doxorubicin and TRAIL administered in
      sequence (Dox-TRAIL). Apoptosis induction was confirmed using a caspase-3
      activity assay. Comparative proteomic analysis between whole cell lysates of Dox
      TRAIL and control samples revealed 56 differentially expressed spots (>=2-fold
      change and p < 0.05) common to at least two cell lines. Of these, 19 proteins
      were identified yielding 11 unique protein identities: CFL1, EIF5A, HNRNPK, KRT8,
      KRT18, LMNA, MYH9, NACA, RPLP0, RPLP2, and RAD23B. A subset of the identified
      proteins was validated by selected reaction monitoring (SRM) and Western
      blotting. Pathway analysis revealed that the differentially abundant proteins
      were associated with cell death, cellular organization, integrin-linked kinase
      signaling, and actin cytoskeleton signaling pathways. The 2D-DIGE analysis has
      yielded candidate biomarkers of response to treatment in breast cancer cell
      models. Their clinical utility will depend on validation using patient breast
      biopsies pre- and post-treatment with anticancer drugs.

PMID- 22133147
TI  - Characterization of monofloral honeys with multivariate analysis of their
      chemical profile and antioxidant activity.
AB  - Various bioactive chemical constituents were quantified for 21 honey samples
      obtained at Rio de Janeiro and Minas Gerais, Brazil. To evaluate their
      antioxidant activity, 3 different methods were used: the ferric reducing
      antioxidant power, the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging
      activity, and the 2,2'-azinobis (3-ethylbenzothiazolin)-6-sulfonate (ABTS)
      assays. Correlations between the parameters were statistically significant (
      0.6684 <= r <=-0.8410, P < 0.05). Principal component analysis showed that honey
      samples from the same floral origins had more similar profiles, which made it
      possible to group the eucalyptus, morrao de candeia, and cambara honey samples in
      3 distinct areas, while cluster analysis could separate the artificial honey from
      the floral honeys. PRACTICAL APPLICATION: This research might aid in the
      discrimination of honey floral origin, by using simple analytical methods in
      association with multivariate analysis, which could also show a great difference
      among floral honeys and artificial honey, indicating a possible way to help with
      the identification of artificial honeys.

PMID- 22133148
TI  - The role of growth temperature in the adhesion and mechanics of pathogenic L.
      monocytogenes: an AFM study.
AB  - The adhesion strengths of pathogenic L. monocytogenes EGDe to a model surface of
      silicon nitride were quantified using atomic force microscopy (AFM) in water for
      cells grown under five different temperatures (10, 20, 30, 37, and 40  degrees
      C). The temperature range investigated was chosen to bracket the thermal
      conditions in which L. monocytogenes survive in the environment. Our results
      indicated that adhesion force and energy quantified were at their maximum when
      the bacteria were grown at 30  degrees C. The higher adhesion observed at 30 
      degrees C compared to the adhesion quantified for bacterial cells grown at 37,
      40, 20, and 10  degrees C was associated with longer and denser bacterial surface
      biopolymer brushes as predicted from fitting a model of steric repulsion to the
      approach distance-force data as well from the results of protein colorimetric
      assays. Theoretically predicted adhesion energies based on soft-particle DLVO
      theory agreed well with the adhesion energies computed from AFM force-distance
      retraction data (r(2) = 0.94); showing a minimum energy barrier to adhesion at 30
      degrees C.

PMID- 22133149
TI  - Influence of DNA extraction and PCR amplification on studies of soil fungal
      communities based on amplicon sequencing.
AB  - Most studies involving next-generation amplicon sequencing of microbial
      communities from environmental studies lack replicates. DNA extraction and PCR
      effects on the variation of read abundances of operational taxonomic units
      generated from deep amplicon 454 pyrosequencing was investigated using soil
      samples from an agricultural field with diseased pea. One sample was extracted
      four times, and one of these samples was PCR amplified four times to obtain eight
      replicates in total. Results showed that species richness was consistent among
      replicates. Variation among dominant taxa was low across replicates, whereas rare
      operational taxonomic units showed higher variation among replicates. The results
      indicate that pooling of several extractions and PCR amplicons will decrease
      variation among samples.

PMID- 22133150
TI  - Maricurvus nonylphenolicus gen. nov., sp. nov., a nonylphenol-degrading bacterium
      isolated from seawater.
AB  - A novel aerobic, Gram-negative bacterial strain, designated KU41E(T), which
      degrades p-n-nonylphenol, was isolated from seawater obtained from the coastal
      region of Ishigaki Island, Japan. Cells are motile, curved rods with a single
      polar flagellum. Strain KU41E(T) grew at 20-35  degrees C, pH 7.0-8.0, in the
      presence of 1.0-4.0% NaCl. The predominant respiratory lipoquinone was ubiquinone
      8, and the major cellular fatty acids were summed feature 3 (C(15:0) iso 2OH
      and/or C(16:1) omega7c, 28.4%), C(18:1) omega7c (19.8%), and C(16:0) (17.0%). The
      DNA G + C content was 48.6 mol%. The 16S rRNA gene sequence analysis indicated
      that strain KU41E(T) is affiliated with the order Alteromonadales within the
      class Gammaproteobacteria and is most closely related to Pseudoteredinibacter
      isoporae SW-11(T) (93.6% similarity) and Teredinibacter turnerae T7902(T) (91.9%
      similarity). On the basis of physiological, chemotaxonomic, and phylogenetic
      data, strain KU41E(T) is suggested to represent a novel species of a new genus,
      for which the name Maricurvus nonylphenolicus gen. nov., sp. nov. is proposed.
      The type strain of M. nonylphenolicus is KU41E(T) (=JCM 17778(T)).

PMID- 22133151
TI  - Complexation of europium(III) by bis(dialkyltriazinyl)bipyridines in 1-octanol.
AB  - The present work focuses on highly selective ligands for An(III)/Ln(III)
      separation: bis(triazinyl)bipyridines (BTBPs). By combining time-resolved laser
      induced fluorescence spectroscopy, nanoelectrospray ionization mass spectrometry,
      vibronic sideband spectroscopy, and X-ray diffraction, we obtain a detailed
      picture of the structure and stoichiometry of the first coordination sphere of
      Eu(III)-BTBP complexes in an octanolic solution. The main focus is on the 1:2
      complexes because extraction studies revealed that those are the species
      extracted into the organic phase. The investigations on europium(III) complexes
      of BTBP with different triazin alkylation revealed differences in the formed
      complexes due to the bulkiness of the ligands. Because of the vibronic sidebands
      in the fluorescence spectra, we were able to detect whether or not nitrate
      ligands are coordinated in the first coordination sphere of the Eu-BTBP
      complexes. In solution, less sterically demanding BTBP offers enough space for
      additional coordination of anions and/or solvent molecules to form 9-coordinated
      Eu-BTBP 1:2 complexes, while bulkier ligands tend to form 8-fold-coordinated
      structures. We also report the first crystal structure of a Ln-BTBP 1:2 complex
      and that of its 1:1 complex, both of which are 10-coordinated.

PMID- 22133152
TI  - The efficacy of Er,Cr:YSGG laser in reconditioning of metallic orthodontic
      brackets.
AB  - OBJECTIVE: This study aimed to evaluate the efficiency of erbium, chromium:
      yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser in removing adhesive from
      bracket bases, and its influence on shear bond strength (SBS) of orthodontic
      brackets, compared to several other recycling methods. BACKGROUND DATA:
      Reconditioning the dislodged attachments is frequently required in orthodontic
      practice to reduce treatment costs. MATERIALS AND METHODS: Seventy-five premolar
      teeth were selected and divided into five groups. In groups 1 to 4, brackets
      recycled with different methods were bonded on the tooth surface, whereas in
      group 5, new brackets were used. The recycling methods were: silicon carbide
      stone grinding (group 1), aluminum oxide sandblasting (group 2), and Er,Cr:YSGG
      laser operated at 3.5 W (group 3) and at 4 W (group 4). The quantitative amount
      of remaining adhesive on the bracket base was determined after recycling using
      stereomicroscopic images, and the SBS values were measured. RESULTS: The
      percentage of adhesive remnants was significantly lower in brackets cleaned with
      aluminum oxide sandblasting, and significantly higher in those grinded by silicon
      carbide stone (p<0.05). Brackets cleaned with silicon carbide stone produced the
      lowest, and those prepared by aluminum oxide blasting or Er,Cr:YSGG laser
      produced the highest SBS among the groups (p<0.05). There was a significant
      correlation between changes in percentage of remaining adhesive on the base after
      recycling with changes in SBS (Pearson r=-0.41, p<0.0001). CONCLUSIONS: Under the
      study conditions, both aluminum oxide blasting and Er,Cr:YSGG laser were
      efficient in removing adhesive from bracket bases, and resulted in significantly
      higher bond strength than for new brackets.

PMID- 22133154
TI  - The effects of parenteral iron dextran and/or desferrioxamine on the development
      of experimental pseudotuberculosis in the domestic chicken (Gallus domesticus).
AB  - Abstract   The development of disease following oral challenge with Yersinia
      pseudotuberculosis (serotype 11) was compared in four groups of five birds
      treated with a parenteral dose of 10 mg iron dextran (Imferon), 10 mg of iron
      dextran plus 10 mg of the chelating agent desferrioxamine (Desferal), 10 mg of
      desferrioxamine or 10 mg of dextran 2 days before the experiment. Four groups of
      two birds received the above treatment regimens but no bacterial challenge. In
      iron dextran treated birds, oral challenge resulted in faecal shedding for the 10
      day duration of the experiment, whereas in those birds which received dextran or
      desferrioxamine alone, the duration of faecal shedding was significantly less.
      Serological titres to the lipopolysaccharide antigen of the challenge bacteria
      were also lower in the groups not pretreated with iron dextran. The birds
      pretreated with iron dextran had diarrhoea and were clinically unwell 2 days
      following the initial oral challenge. Birds not given iron dextran showed no
      clinical signs of disease. Histological examination of five selected areas in the
      liver, spleen and intestine of each bird indicated that birds in the groups
      treated with iron dextran prior to bacterial challenge had significantly more
      intestinal lesions than birds in the groups not treated with iron. In contrast,
      there were significantly more lesions in the spleens of birds not pretreated with
      iron dextran. There was no evidence of stainable iron in the livers of birds
      challenged with Y pseudotuberculosis 10 days after an injection of 10 mg of iron
      dextran. This is in contrast to birds given iron dextran and no bacteria. It was
      concluded that pretreatment of birds with iron dextran resulted in more severe
      clinical disease, prolonged faecal shedding with associated intestinal lesions
      and higher serological titres to bacterial antigen. The number of lesions in the
      spleen and liver was not necessarily correlated with the severity of clinical
      disease, and in all infected birds the hepatic iron levels were significantly
      lower than in the non-infected control birds 10 days after oral challenge. It
      seems probable that the chicken has a high requirement for iron during infection
      with Y pseudotuberculosis and mobilises stored and exogenously supplied iron for
      tissue repair and immunological function.

PMID- 22133153
TI  - Efficacy and safety of a low-energy double-pass 1450-nm diode laser for the
      treatment of acne scars.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a
      1450-nm diode laser on acne scars in Asian patients. BACKGROUND DATA: Acne and
      acne scars affect individuals during puberty and adolescence, and decrease their
      quality of life. METHODS: An open study was performed on 24 Japanese patients (17
      female and 7 male, aged 15-44 years) with acne scars on the face treated with
      five sessions of low-energy double-pass 1450-nm diode laser at 4-week intervals.
      The mean duration of the acne scars prior to receiving laser therapy was 4.8
      years (range 1-9). Clinical evaluation by physicians and with photographs was
      conducted at baseline, 1 month after the final treatment, and at a 3-month follow
      up visit. Topical therapies for acne vulgaris were permitted during the follow-up
      period. RESULTS: All patients completed the five treatment sessions. Seventy-five
      percent of the subjects showed at least 30% improvement of acne scars. At the 3
      month follow-up evaluation, 92.9% of the subjects with >30% improvement
      maintained the effectiveness. Vesicle formation and transient hyperpigmentation
      also occurred in one case. CONCLUSIONS: The 1450-nm diode laser therapy was
      effective and well-tolerated in patients with acne scars, suggesting that this
      may be an appropriate modality for treating facial acne scars.

PMID- 22133155
TI  - Ventral oedema in exotic Angora goats.
AB  - Abstract   A syndrome characterised by ventral oedema and referred to by many
      goat farmers as "water belly". has been recognised in New Zealand in Angora goats
      of South African and Texan origin. It occurs most frequently in young animals in
      the immediate post-shearing period, when as many as 10-15% of the flock may be
      affected to varying degrees. Affected animals are usually bright and alert and
      most will recover spontaneously within 3-4 days. The syndrome may also occur in
      goats suffering from one of a variety of diseases but in some cases there is no
      apparent predisposing cause.

PMID- 22133156
TI  - Ileocolonic aganglionosis in an overo foal.
AB  - Abstract   The American paint horse or pinto (Spanish for painted) has two
      different types within the breed: the overo, which has white patches on a dark
      coat and the tobiano, which has black patches on a white coat. Within the overo
      type the amount of white may be quite small or a horse may be almost entirely
      white, but the basic pattern is that the ventral abdomen is spotted white whilst
      dorsal aspects are dark. The overo is considered to be recessive.

PMID- 22133157
TI  - Rickets in alpacas (Lama pacos) in New Zealand.
AB  - Abstract   Rickets was diagnosed in two weaner alpacas showing ill thrift and
      lameness during the winter of 1992, from a flock at AgResearch Flock House.
      Affected alpacas had abnormally shaped ribs with occasional healing fractures,
      irregular thickening of growth plates and metaphyseal haemorrhages. The mean
      serum phosphorus concentrations of the alpacas fell during June and July, even
      though lambs grazing the same pasture had normal serum phosphorus concentrations
      and the phosphorus concentration of the pasture was considered adequate. Vitamin
      D deficiency may also have contributed to the osteodystrophy. The alpacas had a
      thick fleece during the winter, and diurnal Vitamin D3 synthesis resulting from
      solar irradiation is likely to have been minimal, especially considering the
      reduced sunshine hours recorded during the 1992 winter. Surviving alpacas
      recovered after treatment with monosodium phosphate and an oral Vitamin D
      supplement.

PMID- 22133158
TI  - The pathophysiology and laboratory diagnosis of congenital portosystemic shunts
      in dogs.
AB  - Abstract   Congenital portosystemic shunts generally arise as single vascular
      anomalies that cause the portal blood to bypass the liver and enter the systemic
      venous circulation directly. The liver is primarily affected, as it is deprived
      of perfusion by portal hepatotrophic factors such as insulin, glucagon, and amino
      acids. There is progressive hepatic atrophy, and as a consequence, dysfunction.  
      Hepatic encephalopathy can result from increased levels of ammonia and gamma
      aminobutyric acid within the systemic circulation. Variably toxic amines, captans
      and short chain fatty acids may act as false neurotransmitters. Hypoglycaemia
      will exacerbate the effects of these substances. Increased concentrations of
      ammonia and uric acid in the urine predispose to the precipitation of ammonium
      biurate crystals and the formation of calculi.   Haematological changes include
      anaemia, microcytosis, hypoproteinaemia, leucocytosis, and coagulation
      abnormalities. Gastrointestinal effects are common. They may be displayed as
      anorexia, vomiting, ptyalism, pica, diarrhoea, or polyphagia. Most dogs are less
      than 1 year of age at initial presentation.   Diagnosis from a laboratory
      viewpoint will involve a consideration of the history, clinical findings,
      haematology, serum biochemistry and urinalysis. If the findings are suggestive of
      a congenital portosystemic shunt, the demonstration of elevated fasting or, more
      consistently, post-prandial serum bile acid concentrations, and subsequent
      histological examination of a liver biopsy will provide a definitive diagnosis.

PMID- 22133159
TI  - Hypersensitivity skin testing of lambs infested with the biting louse (Bovicola
      ovis).
AB  - Abstract   Cockle, a defect of lamb's pelts, has recently been shown to be
      associated with infestation of lambs with the louse Bovicoh ovis. The mechanisms
      by which infestation with the louse leads to cockle are not known, but
      immunological hypersensitivity has been suggested. The objectives of our work are
      to determine if lambs respond immunologically to lice and, if so, whether
      hypersensitivity occurs. Preliminary results are presented here.

PMID- 22133160
TI  - Differential diagnosis of tumour-associated hypoglycaemia in small animals.
AB  - Abstract   While there are a number of causes of hypoglycaemia in small animals,
      many of these may be ruled out on the basis of clinical signs, history, age and
      other laboratory results. Further tests for diagnosis include insulin
      measurements, the glucagon tolerance test and glucose administration tests. For
      the diagnosis of insulinomas (beta cell tumours) in dogs, serum insulin and
      glucose concentrations may be measured at the same time and put into the amended
      insulin to glucose ratio (AIGR), which is reportedly the most accurate method of
      diagnosis. The ratio provides an indication of whether or not the serum
      concentration of insulin is appropriate for the concentration of glucose. The
      value of this ratio in cats is not known because there are so few reports of
      insulinomas in this species. In cats it may be better to simply compare insulin
      and glucose levels to see if they are appropriate. The occasional false-positive
      AIGR has been reported in dogs with other tumours and severe sepsis, but with
      these conditions the insulin is usually also low. Insulin to glucose and glucose
      to insulin ratios may also be calculated but are considered less useful than the
      AIGR. The glucagon tolerance test is considered less accurate than the AIGR but
      may be used instead of, or in addition to, the AIGR if results of the AIGR are
      equivocal.

PMID- 22133161
TI  - Polycystic kidney disease in goldfish (Cusrassius auratus).
AB  - Abstract   Thirty percent of 60 goldfish in an outside pond showed progressive
      development of swollen abdomens and floatation problems. The occasional fish was
      found dead.   Necropsy of an affected fish showed an abdomen almost filled with a
      large bilobed ventral mass comprised of masses of cysts filled with clear fluid.
      On histopathological examination, this mass appeared to be composed of large
      cystic spaces lined by a single flattened epithelium. Occasional remnants of
      normal kidney tissue were seen withen the mass.

PMID- 22133162
TI  - An epidermolysis bullosa in a Galloway calf.
AB  - Abstract   A congenital skin disease characterised by mild erosion and ulceration
      of areas exposed to trauma was seen in a 3-day-old Galloway Calf. Bilateral,
      almost symmetrical erosions were Seen On the cheeks, 'PPer and lower lips, nasal
      plane, hard palate and dorsal surface of the tongue. There was also loss of skin
      and ulceration from anterior areas of the carpi, upper fetlocks and coronary band
      of both fore and hindlimbs.

PMID- 22133163
TI  - The perivascular spaces of ovine and canine brains.
AB  - Abstract   The specialised histology and anatomy of the central nervous system
      (CNS) is reflected in its pathology. This is particularly so for the
      perivenular/periarterial spaces in which inflammatory cells accumulate in
      inflammation. These spaces, although structurally not lymphatics, act as
      lymphatics draining fluid from brain to subarachnoid space and to lymphatics
      draining to deep cervical lymph nodes. Inflammatory cells may enter or leave the
      CNS by this route. In immune-based inflammation, they are colonised by subsets of
      immune cells allowing the processing of antigen, synthesis of antibody and
      development of cell mediated immune reactions.

PMID- 22133164
TI  - Contribution of bacterial outer membrane vesicles to innate bacterial defense.
AB  - BACKGROUND: Outer membrane vesicles (OMVs) are constitutively produced by Gram
      negative bacteria throughout growth and have proposed roles in virulence,
      inflammation, and the response to envelope stress. Here we investigate outer
      membrane vesiculation as a bacterial mechanism for immediate short-term
      protection against outer membrane acting stressors. Antimicrobial peptides as
      well as bacteriophage were used to examine the effectiveness of OMV protection.
      RESULTS: We found that a hyper-vesiculating mutant of Escherichia coli survived
      treatment by antimicrobial peptides (AMPs) polymyxin B and colistin better than
      the wild-type. Supplementation of E. coli cultures with purified outer membrane
      vesicles provided substantial protection against AMPs, and AMPs significantly
      induced vesiculation. Vesicle-mediated protection and induction of vesiculation
      were also observed for a human pathogen, enterotoxigenic E. coli (ETEC),
      challenged with polymyxin B. When ETEC with was incubated with low concentrations
      of vesicles concomitant with polymyxin B treatment, bacterial survival increased
      immediately, and the culture gained resistance to polymyxin B. By contrast, high
      levels of vesicles also provided immediate protection but prevented acquisition
      of resistance. Co-incubation of T4 bacteriophage and OMVs showed fast,
      irreversible binding. The efficiency of T4 infection was significantly reduced by
      the formation of complexes with the OMVs. CONCLUSIONS: These data reveal a role
      for OMVs in contributing to innate bacterial defense by adsorption of
      antimicrobial peptides and bacteriophage. Given the increase in vesiculation in
      response to the antimicrobial peptides, and loss in efficiency of infection with
      the T4-OMV complex, we conclude that OMV production may be an important factor in
      neutralizing environmental agents that target the outer membrane of Gram-negative
      bacteria.

PMID- 22133166
TI  - Facile synthesis of flower like copper oxide and their application to hydrogen
      peroxide and nitrite sensing.
AB  - BACKGROUND: The detection of hydrogen peroxide (H2O2) and nitrite ion (NO2-) is
      of great important in various fields including clinic, food, pharmaceutical and
      environmental analyses. Compared with many methods that have been developed for
      the determination of them, the electrochemical detection method has attracted
      much attention. In recent years, with the development of nanotechnology, many
      kinds of micro/nano-scale materials have been used in the construction of
      electrochemical biosensors because of their unique and particular properties.
      Among these catalysts, copper oxide (CuO), as a well known p-type semiconductor,
      has gained increasing attention not only for its unique properties but also for
      its applications in many fields such as gas sensors, photocatalyst and
      electrochemistry sensors. Continuing our previous investigations on transition
      metal oxide including cuprous oxide and alpha-Fe2O3 modified electrode, in the
      present paper we examine the electrochemical and electrocatalytical behavior of
      flower like copper oxide modified glass carbon electrodes (CuO/GCE). RESULTS:
      Flower like copper oxide (CuO) composed of many nanoflake was synthesized by a
      simple hydrothermal reaction and characterized using field-emission scanning
      electron microscopy (FE-SEM) and X-ray diffraction (XRD). CuO modified glass
      carbon electrode (CuO/GCE) was fabricated and characterized electrochemically. A
      highly sensitive method for the rapid amperometric detection of hydrogen peroxide
      (H2O2) and nitrite (NO2-) was reported. CONCLUSIONS: Due to the large specific
      surface area and inner characteristic of the flower like CuO, the resulting
      electrode show excellent electrocatalytic reduction for H2O2 and oxidation of NO2
      . Its sensitivity, low detection limit, fast response time and simplicity are
      satisfactory. Furthermore, this synthetic approach can also be applied for the
      synthesis of other inorganic oxides with improved performances and they can also
      be extended to construct other micro/nano-structured functional surfaces.

PMID- 22133165
TI  - Non-pharmacological, multicomponent group therapy in patients with degenerative
      dementia: a 12-month randomizied, controlled trial.
AB  - BACKGROUND: Currently available pharmacological and non-pharmacological
      treatments have shown only modest effects in slowing the progression of dementia.
      Our objective was to assess the impact of a long-term non-pharmacological group
      intervention on cognitive function in dementia patients and on their ability to
      carry out activities of daily living compared to a control group receiving the
      usual care. METHODS: A randomized, controlled, single-blind longitudinal trial
      was conducted with 98 patients (follow-up: n = 61) with primary degenerative
      dementia in five nursing homes in Bavaria, Germany. The highly standardized
      intervention consisted of motor stimulation, practice in activities of daily
      living, and cognitive stimulation (acronym MAKS). It was conducted in groups of
      ten patients led by two therapists for 2 hours, 6 days a week for 12 months.
      Control patients received treatment as usual. Cognitive function was assessed
      using the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS
      Cog), and the ability to carry out activities of daily living using the Erlangen
      Test of Activities of Daily Living (E-ADL test) at baseline and after 12 months.
      RESULTS: Of the 553 individuals screened, 119 (21.5%) were eligible and 98
      (17.7%) were ultimately included in the study. At 12 months, the results of the
      per protocol analysis (n = 61) showed that cognitive function and the ability to
      carry out activities of daily living had remained stable in the intervention
      group but had decreased in the control patients (ADAS-Cog: adjusted mean
      difference: -7.7, 95% CI -14.0 to -1.4, P = 0.018, Cohen's d = 0.45; E-ADL test:
      adjusted mean difference: 3.6, 95% CI 0.7 to 6.4, P = 0.015, Cohen's d = 0.50).
      The effect sizes for the intervention were greater in the subgroup of patients (n
      = 50) with mild to moderate disease (ADAS-Cog: Cohen's d = 0.67; E-ADL test:
      Cohen's d = 0.69). CONCLUSIONS: A highly standardized, non-pharmacological,
      multicomponent group intervention conducted in a nursing-home setting was able to
      postpone a decline in cognitive function in dementia patients and in their
      ability to carry out activities of daily living for at least 12 months. TRIAL
      REGISTRATION: http://www.isrctn.com Identifier: ISRCTN87391496.

PMID- 22133167
TI  - Incidental findings on cranial imaging in nonagenarians.
AB  - OBJECT: The aim of this article was to report on the nature and prevalence of
      incidental imaging findings in a consecutive series of patients older than 90
      years of age who underwent intracranial imaging for any reason. METHODS: The
      authors retrospectively reviewed the electronic medical and imaging records of
      consecutive patients who underwent brain MR imaging at a single institution over
      a 153-month interval and were at least 90 but less than 100 years of age at the
      time of the imaging study. The prevalence of lesions by type in this consecutive
      series of MR imaging evaluations was calculated for all patients. The authors
      reviewed the medical record to evaluate whether a change in management was
      recommended based on MR imaging findings. They evaluated patient age at the time
      of death and the time interval between MR imaging and death. RESULTS: The authors
      identified 177 patients who met the study criteria. The group included 119 women
      (67%) and 58 (33%) men. Their mean age was 92.3 +/- 1.8 years. Evidence of acute
      ischemic changes or cerebrovascular accident (CVA) was found in 36 patients
      (20%). Fifteen patients (8%) had an intracranial tumor. Intracranial aneurysms
      were incidentally identified in 6 patients (3%). Chronic subdural hematomas were
      found in 3 patients (2%). Overall, 25 patients (14%) had some change in medical
      management as a result of the MR imaging findings. The most common MR imaging
      finding that resulted in a change in medical management was an acute CVA (p <
      0.0001). The mean time to death from date of MR imaging was 2.5 +/- 2.3 years.
      CONCLUSIONS: Intracranial imaging is rarely performed in patients older than 90
      years. In cases of suspected stroke, MR imaging findings may influence treatment
      decisions. Brain MR imaging studies ordered for other indications in this age
      group rarely influence treatment decisions. Incidentally discovered lesions in
      this age group are generally not treated.

PMID- 22133168
TI  - Strategies for asymptomatic carotid artery stenosis.
AB  - The treatment of asymptomatic carotid artery stenosis (ACAS) has continued to
      evolve for the past 3 decades. With rapidly advancing technology, the results of
      old trials have become obsolete. While there has been little change in the
      efficacy of carotid endarterectomy, there have been vast improvements in both
      medical management and carotid angioplasty with stenting. Finding the best
      therapy for a given patient can therefore be difficult. In this article, the
      authors review the current literature regarding treatment options for ACAS and
      the methods available for stratifying patients who would benefit from surgical
      versus medical treatment.

PMID- 22133169
TI  - The management of incidental low-grade gliomas using magnetic resonance imaging:
      systematic review and optimal treatment paradigm.
AB  - OBJECT: The discovery of incidental low-grade gliomas (LGGs) on MR imaging is
      rare, and currently there is no existing protocol for management of these
      lesions. Various studies have approached the dilemma of managing patients with
      incidental LGGs. While some advocate surgery and radiotherapy, others reserve
      surgery until there is radiological evidence of growth. For neurosurgeons and
      radiologists, determining the course of action after routine brain imaging poses
      not only a medical but also an ethical dilemma. The authors conducted a
      systematic review of case reports and case series in hopes of enhancing the
      current understanding of the management options for these rare lesions. METHODS:
      A PubMed search was performed to include all relevant MR imaging studies in which
      management of suspected incidental LGG was reported. Comparisons were made
      between the surgical treatment arm and the active surveillance arm in terms of
      outcome, mode of discovery, reasons for treatment, and histology. RESULTS: Nine
      studies with 72 patients were included in this study (56 in the surgical arm and
      16 in the active surveillance arm). Within the surgical arm, 49% remained deficit
      free after treatment, 25% showed evidence of tumor progression, 13% underwent a
      second treatment, and 7% died. The active surveillance group resulted in no
      unanticipated adverse events, with serial imaging revealing no tumor growth in
      all cases. Lesion regression was reported in 31% of this group. The surgical
      arm's mortality rate was 7% compared with 0% in the active surveillance arm.
      CONCLUSIONS: Treatment decisions for incidental LGG should be individualized
      based on presenting symptoms and radiological evidence of growth. The
      asymptomatic patient may be monitored safely with serial MR imaging and
      occasionally PET scanning before treatment is initiated. In patients presenting
      with nonspecific symptoms or concurrent symptomatic lesions, treatment may be
      initiated earlier to reduce potential morbidity. All treatment decisions must be
      tempered by patient factors and expectations of anticipated benefit.

PMID- 22133170
TI  - Incidental vertebral lesions.
AB  - Incidental vertebral lesions on imaging of the spine are commonly encountered in
      clinical practice. Contributing factors include the aging population, the
      increasing prevalence of back pain, and increased usage of MR imaging.
      Additionally, refinements in CT and MR imaging have increased the number of
      demonstrable lesions. The management of incidental findings varies among
      practitioners and commonly depends more on practice style than on data or
      guidelines. In this article we review incidental findings within the vertebral
      column and review management of these lesions, based on available Class III data.

PMID- 22133171
TI  - Discovery of asymptomatic moyamoya arteriopathy in pediatric syndromic
      populations: radiographic and clinical progression.
AB  - OBJECT: Limited data exist to guide management of incidentally discovered
      pediatric moyamoya. Best exemplified in the setting of unilateral moyamoya, in
      which the unaffected side is monitored, this phenomenon also occurs in
      populations undergoing routine surveillance of the cerebral vasculature for other
      conditions, such as sickle cell disease (SCD) or neurofibromatosis Type 1 (NF1).
      The authors present their experience with specific syndromic moyamoya populations
      to better characterize the natural history of radiographic and clinical
      progression in patients with asymptomatic moyamoya. METHODS: The authors
      performed a retrospective review of the clinical database of the neurosurgery
      department at Children's Hospital Boston, including both nonoperative referrals
      and a consecutive series of 418 patients who underwent surgical revascularization
      for moyamoya disease between 1988 and 2010. RESULTS: Within the period of time
      studied, 83 patients were asymptomatic at the time of radiographic diagnosis of
      moyamoya, while also having either unilateral moyamoya or moyamoya in association
      with either SCD or NF1. The mean age at presentation was 9.1 years (range 1-21
      years), and there were 49 female (59%) and 34 male (41%) patients. The mean
      follow-up duration was 5.4 +/- 3.8 years (mean +/- SD), with 45 patients (54%)
      demonstrating radiographic progression and 37 (45%) becoming symptomatic within
      this period. Patients with SCD had the highest incidence of both radiographic (15
      patients [75%]) and clinical (13 patients [65%]) progression, followed by NF1 (20
      patients [59%] with radiographic progression and 15 patients [44%] with clinical
      progression) and patients with unilateral moyamoya (10 patients [35%] with
      radiographic progression and 9 patients [31%] with clinical progression).
      CONCLUSIONS: Radiographic progression occurred in the majority of asymptomatic
      patients and generally heralded subsequent clinical symptoms. These data
      demonstrate that moyamoya is a progressive disorder, even in asymptomatic
      populations, and support the rationale of early surgical intervention to minimize
      morbidity from stroke.

PMID- 22133172
TI  - Natural history of untreated syringomyelia in pediatric patients.
AB  - OBJECT: The natural history of syringomyelia in pediatric patients remains
      uncertain. Although symptomatic and operative cases of syringomyelia are well
      studied, there are fewer articles in the literature on the nonoperative syrinx
      and its clinical and radiological course. The purpose of this research was to
      analyze the natural history of untreated syringomyelia in pediatric patients
      presenting with minimal neurological symptoms. METHODS: A review of the
      neurosurgery database at British Columbia's Children's Hospital identified all
      pediatric patients (< 18 years of age) with syringes identified on MR imaging.
      Patients were included in this study if they had at least 2 MR images of the
      spine, at least 1 year apart, while receiving nonoperative treatment. Magnetic
      resonance imaging was used to determine changes in the size of the syrinx over
      time. Clinic notes were analyzed to establish demographic and clinical features
      and to determine any clinical changes over time. RESULTS: A total of 17 patients
      were included in the study. Symptoms at presentation were often mild and included
      limb numbness (3 cases), headaches (2 cases), mild sensory deficits (2 cases),
      mild motor deficits (3 cases), and intermittent incontinence (7 cases). The
      consultant neurosurgeon believed that the syrinx was not contributing to the
      symptoms in these 17 patients. The syrinx either remained unchanged (7 cases) or
      diminished in size (8 cases) in a total of 15 patients (88%). In the remaining 2
      patients the authors noted an increase in syrinx size, in 1 of whom the clinical
      course also worsened. Both of these patients had a Chiari malformation and
      subsequently underwent craniocervical decompression. Overall, the mean change was
      -0.7 mm of maximal axial diameter (range -2.6 to +2.7 mm). Sixteen patients (94%)
      exhibited no worsening of symptoms over time. CONCLUSIONS: Syringomyelia often
      remains stable in patients receiving nonoperative treatment. However, given that
      2 (12%) of 17 syringes in this series enlarged, it is likely appropriate to
      include periodic imaging in the follow-up of these cases.

PMID- 22133173
TI  - Incidental pituitary adenomas.
AB  - OBJECT: Pituitary incidentalomas are a common finding with a poorly understood
      natural history. Over the last few decades, numerous studies have sought to
      decipher the optimal evaluation and treatment of these lesions. This paper aims
      to elucidate the current evidence regarding their prevalence, natural history,
      evaluation, and management. METHODS: A search of articles on PubMed (National
      Library of Medicine) and reference lists of all relevant articles was conducted
      to identify all studies pertaining to the incidence, natural history, workup,
      treatment, and follow-up of incidental pituitary and sellar lesions,
      nonfunctioning pituitary adenomas, and incidentalomas. RESULTS: The reported
      prevalence of pituitary incidentalomas has increased significantly in recent
      years. A complete history, physical, and endocrinological workup with formal
      visual field testing in the event of optic apparatus involvement constitutes the
      basics of the initial evaluation. Although data regarding the natural history of
      pituitary incidentalomas remain sparse, they seem to suggest that progression to
      pituitary apoplexy (0.6/100 patient-years), visual field deficits (0.6/100
      patient-years), and endocrine dysfunction (0.8/100 patient-years) remains low. In
      larger lesions, apoplexy risk may be higher. CONCLUSIONS: While the majority of
      pituitary incidentalomas can be managed conservatively, involvement of the optic
      apparatus, endocrine dysfunction, ophthalmological symptoms, and progressive
      increase in size represent the main indications for surgery.

PMID- 22133174
TI  - Spontaneous resolution of an infantile hemangioma in a dorsal root ganglion.
AB  - Infantile hemangiomas are tumors commonly seen in children. Few authors have
      reported infantile hemangiomas affecting the CNS, and there are no prior reports
      detailing spontaneous resolution of a histologically proven juvenile hemangioma
      within a dorsal root ganglion. The authors report the case of a newborn boy with
      a large cutaneous hemangioma in the midline of his back. Spinal MR images were
      obtained to rule out associated spinal cord tethering, and an intradural spinal
      lesion was unexpectedly discovered. Biopsy revealed an intradural infantile
      hemangioma within the dorsal root ganglion, and, based on this diagnosis, no
      resection was performed. Sixteen months following the biopsy, the cutaneous
      hemangioma had become involuted and the intradural hemangioma had completely
      resolved. The behavior of the intradural component in this case follows the
      natural history of many cutaneous infantile hemangiomas.

PMID- 22133175
TI  - Incidentally discovered lesions.

PMID- 22133176
TI  - The case for family screening for intracranial aneurysms.
AB  - Given that relatives of patients with intracranial aneurysms (IAs) or
      subarachnoid hemorrhage have a greater risk of harboring an aneurysm, family
      screening has become a common practice in neurosurgery. Unclear data exist
      regarding who should be screened and at what age and interval screening should
      occur. Multiple factors including the natural history of IAs, the risk of
      treatment, the cost of screening, and the psychosocial impact of finding an
      aneurysm should be taken into account when family screening is considered. In
      this paper, the authors review the current literature regarding risk factors and
      natural history of sporadic and familial aneurysms. Based on these data the
      authors assess current recommendations for screening and propose their own
      recommendations.

PMID- 22133177
TI  - Management of incidental cavernous malformations: a review.
AB  - Cavernous malformations (CMs) are angiographically occult vascular malformations
      that are frequently found incidentally on MR imaging. Despite this benign
      presentation, these lesions could cause symptomatic intracranial hemorrhage,
      seizures, and focal neurological deficits. Cavernomas can be managed
      conservatively with neuroimaging studies, surgically with lesion removal, or with
      radiosurgery. Considering recent studies examining the CM's natural history,
      imaging techniques, and possible therapeutic interventions, the authors provide a
      concise review of the literature and discuss the optimal management of incidental
      CMs.

PMID- 22133178
TI  - Management of incidentally discovered intracranial vascular abnormalities.
AB  - With the widespread use of brain imaging studies, neurosurgeons have seen a
      marked increase in the number of incidental intracranial lesions, including
      vascular abnormalities. Specifically, the detection of incidentally discovered
      aneurysms, arteriovenous malformations, cavernous angiomas, developmental venous
      anomalies, and capillary telangiectasias has increased. The best management
      strategy for most of these lesions is controversial. Treatment options include
      observation, open surgery, endovascular procedures, and radiosurgery. Multiple
      factors should be taken into account when discussing treatment indications,
      including the natural history of the disease and the risk of the treatment. In
      this article, the authors focus on the natural history of these lesions and the
      risk of the treatment, and they give recommendations regarding the most
      appropriate management strategy based on the current evidence in the literature
      and their experience with intracranial vascular abnormalities.

PMID- 22133179
TI  - Incidental findings of mass lesions on neuroimages in children.
AB  - Increasing use of neuroimaging in children has led to more incidental findings of
      CNS mass lesions, the management of which is uncertain. The authors' aims in this
      study are to describe these mass lesions and their evolution, as well as to
      discuss the management options and determine the prevalence of incidental CNS
      mass lesions at their pediatric clinic. A retrospective study was undertaken in
      children with primary CNS tumors who were younger than 18 years old and were
      admitted to the University Children's Hospital of Zurich, Switzerland, between
      January 1995 and December 2010. In 19 (5.7%) of 335 patients with newly diagnosed
      CNS tumors, the diagnosis of a CNS mass lesion was an incidental finding. Reasons
      for obtaining neuroimages in these 19 patients were head trauma (in 6 patients);
      research protocols (in 3); nasal/orbital malformations (in 2); endocrinological
      and psychiatric evaluations (in 2); and vertebral bone anomaly without
      neurological signs, absence seizures, congenital ataxia, recurrent vomiting,
      developmental delay, and "check-up" at the explicit request of the parents (in 1
      patient each). Seven patients underwent immediate surgery for low-grade glioma (4
      patients) and craniopharyngioma, ependymoma, and choroid plexus papilloma (1
      patient each); and 12 were treated conservatively or were observed. Ten of 12
      conservatively treated patients remained stable (median follow-up time 1.8 years)
      and the other 2 underwent delayed surgery because of tumor progression
      (medulloblastoma in one patient and fibrillary astrocytoma in the other).  
      Clinicians are increasingly challenged by the discovery of incidental CNS mass
      lesions. A subgroup of such lesions (with typical imaging patterns such as tectal
      glioma and dysembryoplastic neuroepithelial tumor) can be monitored
      conservatively, clinically, and radiographically. Future prospective studies are
      needed to define optimal management strategies based on larger collections of
      natural histories, as well as to assess the true prevalence of incidental CNS
      mass lesions.

PMID- 22133180
TI  - Clinical considerations in the management of asymptomatic carotid artery
      stenosis.
AB  - Incidental findings pose considerable management dilemmas for the treating
      physician and psychological burden for the respective patient. With an aging
      population, more patients will be diagnosed with asymptomatic internal carotid
      artery stenosis. Patients will have to be counseled with regard to treatment
      options according to their individual risk profile and according to
      professionals' knowledge of evidence-based data derived from large randomized
      control trials. Treatment consensus has long been lacking for patients with
      asymptomatic carotid artery stenosis prior to any randomized controlled trials.
      Additionally, an individual's risk profile may be hard to assess according to
      knowledge gained from randomized controlled trials. Moreover, while earlier
      studies compared carotid endarterectomy and medical therapy, in the past years, a
      new therapeutic modality, carotid artery angioplasty and stenting, has emerged as
      a possible alternative. This has been evaluated in a recent randomized controlled
      trial, the Carotid Revascularization Endarterectomy versus Stenting Trial
      (CREST), which compared carotid endarterectomy with angioplasty and stenting in
      both symptomatic and asymptomatic patients. The following review summarizes
      current knowledge of the natural history, diagnosis, and treatment strategies to
      counsel patients with asymptomatic carotid artery stenosis.

PMID- 22133181
TI  - Tarlov cysts: a controversial lesion of the sacral spine.
AB  - The primary aim of our study was to provide a comprehensive review of the
      clinical, imaging, and histopathological features of Tarlov cysts (TCs) and to
      report operative and nonoperative management strategies in patients with sacral
      TCs. A literature review was performed to identify articles that reported
      surgical and nonsurgical management of TCs over the last 10 years. Tarlov cysts
      are often incidental lesions found in the spine and do not require surgical
      intervention in the great majority of cases. When TCs are symptomatic, the
      typical clinical presentation includes back pain, coccyx pain, low radicular
      pain, bowel/bladder dysfunction, leg weakness, and sexual dysfunction. Tarlov
      cysts may be revealed by MR and CT imaging of the lumbosacral spine and must be
      meticulously differentiated from other overlapping spinal pathological entities.
      They are typically benign, asymptomatic lesions that can simply be monitored. To
      date, no consensus exists about the best surgical strategy to use when indicated.
      The authors report and discuss various surgical strategies including posterior
      decompression, cyst wall resection, CT-guided needle aspiration with
      intralesional fibrin injection, and shunting. In operative patients, the rates of
      short-term and long-term improvement in clinical symptoms are not clear. Although
      neurological deficit frequently improves after surgical treatment of TC, pain is
      less likely to do so.

PMID- 22133182
TI  - Incidental meningiomas.
AB  - With the increasing availability and use of modern brain diagnostic imaging
      modalities, discovery of incidental meningiomas has become fairly common. This
      creates a dilemma among neurosurgeons as to whether these lesions should be
      treated. Numerous natural history studies have been published in an effort to
      shed light on the potential for growth of incidental meningiomas. The available
      data appear to suggest that these tumors can fall into 1 of 3 main growth
      patterns: no growth, linear growth, or exponential growth. The therapeutic
      strategy selected should also consider several other factors, mainly the risk of
      complications from an eventual surgery, the possibility of malignancies and other
      pathological conditions that mimic meningiomas, and the age and medical condition
      of the patient. The authors believe that most asymptomatic incidental meningiomas
      can be observed using serial imaging and clinical follow-up evaluations. Surgical
      interventions are typically reserved for large, symptomatic lesions and those
      with documented potential for significant growth.

PMID- 22133183
TI  - Idiopathic syringomyelia: retrospective case series, comprehensive review, and
      update on management.
AB  - OBJECT: A syrinx is a fluid-filled cavity within the spinal cord that can be an
      incidental finding or it can be accompanied by symptoms of pain and temperature
      insensitivity. Although it is most commonly associated with Chiari malformation
      Type I, the advancement of imaging techniques has resulted in more incidental
      idiopathic syringes that are not associated with Chiari, tumor, trauma, or
      postinfectious causes. The authors present a comprehensive review and management
      strategies for the idiopathic variant of syringomyelia. METHODS: The authors
      retrospectively identified 8 idiopathic cases of syringomyelia at their
      institution during the last 6 years. A PubMed/Medline literature review yielded
      an additional 38 articles. RESULTS: Two of the authors' patients underwent
      surgical treatment that included a combination of laminectomy, lysis of
      adhesions, duraplasty, and syrinx fenestration. The remaining 6 patients were
      treated conservatively and had neurologically stable outcomes. Review of the
      literature suggests that an etiology-driven approach is essential in the
      diagnosis and management of syringomyelia, although conservative management
      suffices for most cases. In particular, it is important to look at disturbances
      in CSF flow, as well as structural abnormalities including arachnoid webs, cysts,
      scars, and a diminutive posterior fossa. CONCLUSIONS: The precise etiology for
      idiopathic syringomyelia (IS) is still unclear, although conceptual advances have
      been made toward the overall understanding of the pathophysiology of IS. Various
      theories include the cerebellar piston theory, intramedullary pulse pressure
      theory, and increased spinal subarachnoid pressure. For most patients with IS,
      conservative management works well. Continued progression of symptoms, however,
      could be approached using decompressive strategies such as laminectomy, lysis of
      adhesions, and craniocervical decompression, depending on the level of pathology.
      Management for patients with progressive neurological dysfunction and the lack of
      flow disturbance is unclear, although syringosubarachnoid shunting can be
      considered.

PMID- 22133184
TI  - Small incidentally found aneurysms.

PMID- 22133185
TI  - Incidental os odontoideum: current management strategies.
AB  - Os odontoideum was first described in the late 1880s and still remains a mystery
      in many respects. The genesis of os odontoideum is thought to be prior bone
      injury to the odontoid, but a developmental cause probably also exists. The
      spectrum of presentation is striking and ranges from patients who are
      asymptomatic or have only neck pain to those with acute quadriplegia, chronic
      myelopathy, or even sudden death. By definition, the presence of an os
      odontoideum renders the C1-2 region unstable, even under physiological loads in
      some patients. The consequences of this instability are exemplified by numerous
      cases in the literature in which a patient with os odontoideum has suffered a
      spinal cord injury after minor trauma. Although there is little debate that
      patients with os odontoideum and clinical or radiographic evidence of
      neurological injury or spinal cord compression should undergo surgery, the
      dispute continues regarding the care of asymptomatic patients whose os
      odontoideum is discovered incidentally. The authors' clinical experience leads
      them to believe that certain subgroups of asymptomatic patients should be
      strongly considered for surgery. These subgroups include those who are young,
      have anatomy favorable for surgical intervention, and show evidence of
      instability on flexion-extension cervical spine x-rays. This recommendation is
      bolstered by the fact that surgical fusion of the C1-2 region has evolved greatly
      and can now be done with considerable safety and success. When atlantoaxial
      instrumentation is used, fusion rates for os odontoideum should approach 100%.

PMID- 22133186
TI  - Small (< 10-mm) incidentally found intracranial aneurysms, Part 1: reasons for
      detection, demographics, location, and risk factors in 212 consecutive patients.
AB  - OBJECT: The widespread use of imaging techniques for evaluating nonspecific
      symptoms (vertigo, dizziness, memory concerns, unsteadiness, and the like) and
      focal neurological symptoms related to cerebrovascular disease has led to
      increased identification of asymptomatic incidentally discovered unruptured
      intracranial aneurysms (UIAs). The management of these incidental aneurysms is
      controversial and many factors need to be considered. The authors describe
      reasons leading to diagnosis, demographics, and risk factors in a large
      consecutive series of patients with small incidentally found UIAs. METHODS: The
      authors prospectively evaluated 335 patients harboring 478 small (< 10-mm) UIAs
      between January 2008 and May 2011. Patients with known aneurysms, possibly
      symptomatic aneurysms, arteriovenous malformation-related aneurysms, patients
      with a history of subarachnoid hemorrhage from another aneurysm, and patients
      harboring extradural aneurysms were excluded from the analysis. Only truly
      incidental small aneurysms (272 aneurysms in 212 patients) were considered for
      the present analysis. Data regarding the reason for detection, demographics,
      location, and presence of potential risk factors for aneurysm formation were
      prospectively collected. RESULTS: There were 158 female (74.5%) and 54 male
      (25.5%) patients whose mean age was 60.6 years (median 62 years). The most common
      reason for undergoing the imaging study that led to a diagnosis of the aneurysms
      was evaluation for nonspecific spells and symptoms related to focal
      cerebrovascular ischemia (43.4%), known/possible intracranial or neck pathology
      (24%), and headache (16%). The most common location (27%) of the aneurysm was the
      middle cerebral artery; the second most common (22%) was the paraclinoid internal
      carotid artery (excluding cavernous sinus aneurysms). Sixty-nine percent of
      patients were current or prior smokers, 60% had a diagnosis of hypertension, and
      23% had one or more relatives with a history of intracranial aneurysms with or
      without subarachnoid hemorrhage. CONCLUSIONS: Small incidental UIAs are more
      commonly diagnosed in elderly individuals during imaging performed to investigate
      ill-defined spells or focal cerebrovascular ischemic symptoms, or during the
      evaluation of known or probable unrelated intracranial/neck pathology.
      Hypertension, smoking, and family history of aneurysms are common in this patient
      population, and the presence of these risk factors has important implications for
      treatment recommendations. Although paraclinoid aneurysms (excluding
      intracavernous aneurysms) are uncommon in patients with ruptured intracranial
      aneurysms, this location is very common in patients with small incidental UIAs.

PMID- 22133187
TI  - Small (< 10-mm) incidentally found intracranial aneurysms, Part 2: treatment
      recommendations, natural history, complications, and short-term outcome in 212
      consecutive patients.
AB  - OBJECT: The management of incidental small unruptured intracranial aneurysms
      (UIAs) is controversial and many factors need to be considered in the decision
      making process. The authors describe a large consecutive series of patients
      harboring small incidental intracranial aneurysms. Treatment strategy, natural
      history, complications, and short-term outcomes are presented. METHODS: Between
      January 2008 and May 2011, the authors prospectively evaluated 212 patients with
      272 small (< 10-mm) incidental aneurysms. Treatment recommendations (observation,
      endovascular treatment, or surgery), complications of treatment, and short-term
      outcomes were assessed. RESULTS: Recommended treatment consisted of observation
      in 125 patients, endovascular embolization in 64, and surgery in 18. Six patients
      were excluded from further analysis because they underwent treatment elsewhere.
      In the observation group, at a mean follow-up of 16.7 months, only 1 patient was
      moved to the embolization group. Seven (6%) of the 125 patients in the
      observation group died of causes unrelated to aneurysm. Sixty-five patients
      underwent 69 embolization procedures. The periprocedural permanent morbidity and
      mortality rates in patients undergoing endovascular treatment were 1.5% and 1.5%,
      respectively (overall morbidity and mortality rate 3.0%). In the surgery group no
      periprocedural complications were observed, although 1 patient did not return to
      her previous occupation. No aneurysmal rupture was documented in any of the 3
      treatment groups during the follow-up period. CONCLUSIONS: A cautious and
      individualized approach to incidental UIAs is of utmost importance for
      formulation of a safe and effective treatment algorithm. Invasive treatment
      (either endovascular or surgery) can be considered in selected younger patients,
      certain "higher-risk" locations, expanding aneurysms, patients with a family
      history of aneurysmal hemorrhage, and in those who cannot live their lives
      knowing that they harbor the UIA. Although the complication rate of invasive
      treatment is very low, it is not negligible. The study confirms that small
      incidental UIAs deemed to be not in need of treatment have a very benign short
      term natural history, which makes observation a reasonable approach in selected
      patients.

PMID- 22133188
TI  - Identification of virulence factors in  Vibrio cholerae  isolated from Iraq
      during the 2007-2009 outbreak.
AB  - Thousands of people were infected with  Vibrio cholerae  during the outbreak in
      Iraq in 2007-2009. Vibrio cholerae was shown to be variable in its content of
      virulence determinants and in its antibiotic sensitivity. This study was designed
      to isolate and characterize clinical and environmental V. cholerae isolates and
      to determine  antibiotic sensitivity, enzyme and toxin production,  and the
      presence of virulence genes. Eighty clinical and five environmental bacterial
      isolates were collected and diagnosed by subjecting them to microscopic,
      biochemical, serological, and molecular analysis. The results revealed that 55%
      of clinical isolates belonged to the Inaba serotype, 32.5% to the Ogawa
      serotypes, and 12.5% to the Non-O1 serotype. All environmental V. cholerae
      isolates belonged to the Non-O1 serotype. All environmental isolates were
      sensitive to all examined antimicrobial agents, while all clinical isolates
      showed a high sensitivity (100%) to ampicillin, gentamicin, cephalothin,
      tetracycline, erythromycin, and ciprofloxacin, and a high resistance (97.5%) to
      co-trimoxazole, nalidixic acid, and chloramphenicol. It was found that all V.
      cholerae (O1) isolates were resistant to the Vibrio static O129 and all Non-O1 V.
      cholerae isolates were sensitive to the Vibrio static O129. All clinical and
      environmental isolates produced hemolysin (100%) and lecithinase (100%), while
      they showed various production rates of protease (90% of clinical and 60% of
      environmental) and lipase (50% of clinical and 20% of environmental). The ompW
      gene was amplified in all the clinical and environmental V. cholerae isolates,
      but not in other related and nonrelated bacteria. Multiplex PCR analysis showed
      that the toxR gene was amplified in all clinical and environmental isolates,
      while ctxA, ctxB, tcpA genes were amplified only in clinical (O1) isolates. This
      study indicates the differences in the production of some enzymes and toxins and
      in the content of virulence genes between clinical and environmental isolates in
      Iraq during the outbreak (2007-2009).

PMID- 22133190
TI  - Investigation of the role of ZurR in the physiology and pathogenesis of Listeria
      monocytogenes.
AB  - Listeria monocytogenes is a Gram positive pathogen that is ubiquitous in the
      environment. It is a facultative anaerobic rod that causes listeriosis, a disease
      with potentially lethal consequences for susceptible individuals. During
      infection, the pathogen is capable of sequestering metal ions to act as vital
      biocatalysts in cellular processes. The zinc uptake regulator (ZurR) is predicted
      to coordinate uptake of zinc from the external environment. An in-frame deletion
      of the zurR gene resulted in a mutant exhibiting a small colony phenotype and a
      smaller cell size. The zurR mutant was unaffected under conditions of zinc
      limitation but demonstrated increased sensitivity to toxic levels of zinc. The
      mutant also demonstrated a significant (1-log) reduction in virulence potential
      in the murine model of infection. Using a bioinformatic approach, we identified a
      number of potentially Zur-regulated genes in the genome of L. monocytogenes.
      Quantitative RT-PCR demonstrated significant de-repression of zurA, lmo0153, and
      lmo1671 in the zurR mutant background indicating that these putative transporters
      are ZurR regulated.

PMID- 22133191
TI  - Heme oxygenase-1 expression in the ovary dictates a proper oocyte ovulation,
      fertilization, and corpora lutea maintenance.
AB  - PROBLEM: Animals deficient in Heme oxygenase-1 (HO-1, Hmox1(-/-) mice) have
      impaired pregnancies, characterized by intrauterine fetal death. HO-1 expression
      has been shown to be essential for pregnancy by dictating placentation and
      intrauterine fetal development. Its absence leads to intrauterine fetal growth
      restriction and fetal loss, which is independent of the immune system. Defect in
      previous steps, e.g., ovulation, may, however, also count for their poor
      reproductive outcome. METHOD OF STUDY: Here, we investigated ovulation after
      hormonal hyperstimulation in Hmox1 wild-type and knockout animals. RESULTS AND
      CONCLUSIONS: We observed that animals lacking HO-1 produced significantly less
      oocytes after hormonal stimulation than wild type animals and this was mirrored
      by the number of corpora lutea in the ovary. Furthermore, ovulated oocytes from
      Hmox1(-/-) animals were poorly fertilized compared with those from wild-type
      animals. In conclusion, we demonstrate here that HO-1 plays a pivotal role in the
      process of oocyte ovulation as well as fertilization, bringing to light a new and
      unsuspected role for HO-1.

PMID- 22133189
TI  - Asbestos activates CH12.LX B-lymphocytes via macrophage signaling.
AB  - The impact of asbestos exposure on the development and progression of
      autoimmunity is becoming increasingly recognized as a public health issue.
      Epidemiological studies have shown an association between exposure to airborne
      silicates, such as asbestos, and autoimmunity, but the etiology remains
      unresolved. B1a B-lymphocytes have been implicated in autoimmune responses in
      mice, and splenic B1a cell numbers are altered following asbestos exposure. The
      purpose of this study was to explore the possible role of B1a B-lymphocytes in
      the production of pathogenic autoantibodies by testing the hypothesis that B1a B
      lymphocytes directly react with asbestos and increase production of antibodies.
      The B1a-like B-lymphocyte model, CH12.LX, was exposed to asbestos in vitro via
      direct and indirect mechanisms. The effect was determined of these exposures on
      the rate of proliferation and on production of various immunoglobulin classes.
      Direct exposure elicited no measurable response by the CH12.LX cells. Culturing
      the CH12.LX cells in media from asbestos-exposed RAW 264.7 macrophages, however,
      decreased the proliferation rate and stimulated the cells to increase production
      of the immunoglobulin isotypes IgG1, IgG3, and IgA. It was discovered that
      asbestos stimulated the macrophages to increase production of the cytokines
      interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Recombinant murine IL-6
      caused similar results seen with the macrophage media, indicating a role of IL-6
      in stimulating a response by the B1a B-lymphocytes to asbestos. In correlation
      with the in vitro data, it was determined ex vivo that exposure of peritoneal
      cells (from C57Bl/6 mice) to asbestos caused an increase in the expression of IL
      6 and TNFalpha, as well as of surface expression of IgA on the peritoneal B1a B
      lymphocytes. These data demonstrate that asbestos leads to immunologic changes
      consistent with activation of B1a B-lymphocytes. This study also provides a model
      for analyzing the critical steps that may be involved in asbestos-induced
      autoimmune responses.

PMID- 22133192
TI  - Age differences in verbal and visuo-spatial working memory updating: evidence
      from analysis of serial position curves.
AB  - Memory updating is the ability to select and update relevant information and
      suppress no-longer-relevant data. The few studies in this area, targeting mainly
      the verbal domain, have investigated and confirmed an age-related decline in
      working memory updating ability (De Beni & Palladino, 2004; Van der Linden,
      Bredart, & Beerten, 1994). The present research examines the ability of younger
      and older adults to update information in verbal and visuo-spatial running memory
      tasks. Results showed that the participants' performance was higher in the verbal
      than in the visuo-spatial task. Nonetheless, independently of the task domain, an
      age-related decline in updating performance was found. Moreover, analysis of
      serial positions suggested that, in the updating procedure, the participants were
      not attempting to actively maintain items, preferring to adopt a low-effort,
      "recency-based" strategy. The use of this type of strategy is more evident in
      older participants, as shown in both the accuracy performance and the proportion
      of intrusion errors.

PMID- 22133193
TI  - Poems by children as patient-reported outcomes.

PMID- 22133195
TI  - Burden of anemia among indigenous populations.
AB  - An international perspective of the magnitude of anemia in indigenous peoples is
      currently lacking. The present systematic review was performed to characterize
      the global prevalence, severity, and etiology of anemia in indigenous peoples by
      conducting a systematic search of original research published in English from
      1996 to February 2010 using PubMed, Medline, and Embase. A total of 50 studies,
      representing the following 13 countries, met the inclusion criteria: Australia,
      Brazil, Canada, Guatemala, India, Kenya, Malaysia, Mexico, New Zealand, Sri
      Lanka, Tanzania, the United States, and Venezuela. Results indicate major
      deficiencies in the coverage and quality of anemia monitoring data for indigenous
      populations worldwide. The burden of anemia is overwhelmingly higher among
      indigenous groups compared to the general population and represents a moderate
      (20-39.9%) to severe (>=40%) public health problem. For the most part, the
      etiology of anemia is preventable and includes inadequate diet, poor living
      conditions, and high infection rates (i.e., malaria and intestinal parasites). A
      concerted global effort is needed to reduce the worldwide burden of anemia in
      these marginalized populations.

PMID- 22133194
TI  - Vaccination with liposomal leishmanial antigens adjuvanted with monophosphoryl
      lipid-trehalose dicorynomycolate (MPL-TDM) confers long-term protection against
      visceral leishmaniasis through a human administrable route.
AB  - The development of a long-term protective subunit vaccine against visceral
      leishmaniasis depends on antigens and adjuvants that can induce an appropriate
      immune response. The immunization of leishmanial antigens alone shows limited
      efficacy in the absence of an appropriate adjuvant. Earlier we demonstrated
      sustained protection against Leishmania donovani with leishmanial antigens
      entrapped in cationic liposomes through an intraperitoneal route. However, this
      route is not applicable for human administration. Herein, we therefore evaluated
      the immune response and protection induced by liposomal soluble leishmanial
      antigen (SLA) formulated with monophosphoryl lipid-trehalose dicorynomycolate
      (MPL-TDM) through a subcutaneous route. Subcutaneous immunization of BALB/c mice
      with SLA entrapped in liposomes or with MPL-TDM elicited partial protection
      against experimental visceral leishmaniasis. In contrast, liposomal SLA
      adjuvanted with MPL-TDM induced significantly higher levels of protection in
      liver and spleen in BALB/c mice challenged 10 days post-vaccination. Protection
      conferred by this formulation was sustained up to 12 weeks of immunization, and
      infection was controlled for at least 4 months of the challenge, similar to
      liposomal SLA immunization administered intraperitoneally. An analysis of
      cellular immune responses of liposomal SLA + MPL-TDM immunized mice demonstrated
      the induction of IFN-gamma and IgG2a antibody production not only 10 days or 12
      weeks post-vaccination but also 4 months after the challenge infection and a down
      regulation of IL-4 production after infection. Moreover, long-term immunity
      elicited by this formulation was associated with IFN-gamma production also by
      CD8+ T cells. Taken together, our results suggest that liposomal SLA + MPL-TDM
      represent a good vaccine formulation for the induction of durable protection
      against L. donovani through a human administrable route.

PMID- 22133196
TI  - Sodium-dependent glucose transporter protein as a potential therapeutic target
      for improving glycemic control in diabetes.
AB  - Glucose is transported across the cell membrane by two different types of glucose
      transporters: glucose-facilitated transporters and sodium-dependent glucose
      transport (SGLT) proteins. Regulation of SGLT activity (namely, inhibition of
      SGLT1 and SGLT2 activity and stimulation of SGLT3 activity) represents a
      potential means of managing hyperglycemia and diabetes, thus preventing
      complications of diabetes. The purpose of the present review is to discuss the
      role of SGLT proteins in the pathophysiology of diabetes and to describe the
      mechanisms by which these transporters may be used for glycemic control and the
      treatment of diabetes. The regulatory processes involved in SGLT-mediated glucose
      uptake are also described briefly. This information provides new insight into the
      complementary mechanisms involved in the regulation of SGLT-mediated glucose
      transport as well as a basis for further investigation.

PMID- 22133198
TI  - Relationship between smoking and metabolic syndrome.
AB  - Obesity and smoking are important causes of morbidity and mortality worldwide.
      The diseases and conditions associated with smoking make tobacco use one of the
      leading causes of death worldwide. In the World Health Organization European
      region, overweight and obesity are responsible for many chronic diseases, causing
      more than one million deaths each year. Smoking cessation is associated with a
      significantly reduced mortality risk in every body-mass-index group. Reductions
      in smoking and obesity would increase both the psychophysical well-being of the
      population and its economic productivity; it would also reduce the direct costs
      of pharmacological therapies and other forms of treatment. The aim of this review
      is to critically evaluate how tobacco smoking and obesity interact to reduce life
      expectancy, and to offer a comprehensive view of this issue that should be useful
      for clinical practice.

PMID- 22133200
TI  - An improved immunoblotting technique for the serodiagnosis of Brucella ovis
      infections.

PMID- 22133201
TI  - 1/25 translocations in Blonde d'Aquitaine cattle in New Zealand.

PMID- 22133202
TI  - Demineralized bone particle impregnated poly(l-lactide-co-glycolide) scaffold for
      application in tissue-engineered intervertebral discs.
AB  - Demineralized bone particle (DBP) contains powerful bioactive molecules that
      facilitate new bone or cartilage growth. We developed hybrid scaffolds of poly(l
      lactide-co-glycolide) (PLGA) with various concentrations of DBP (DBP/PLGA), of
      which phenotypes on intervertebral disc (IVD) cells were investigated. The hybrid
      scaffold has a cylindrical donut shape with two distinct parts; the inner is for
      the nucleus pulposus (NP) and the outer is for annulus fibrosus (AF). Rabbit NP
      and AF cells were seeded into the inner and outer regions of the DBP/PLGA
      scaffolds separately. Disc cell viability in DBP/PLGA scaffolds was superior to
      pure PLGA scaffold and increased with increasing DBP concentration. In vitro- and
      in vivo-formed tissues were characterized by RT-PCR, Safranin-O, Masson's
      trichrome staining and immunohistochemi- cal staining for type-I and type-II
      collagen. DBP/PLGA hybrid scaffolds revealed more active expression of disc
      phenotypes, as characterized by protein and mRNA expression, than the PLGA
      control. This study provides valuable information for potential disc replacement
      using DBP and PLGA. 

PMID- 22133197
TI  - The Mediterranean diet: effects on proteins that mediate fatty acid metabolism in
      the colon.
AB  - A Mediterranean diet appears to have health benefits in many domains of human
      health, mediated perhaps by its anti-inflammatory effects. Metabolism of fatty
      acids and subsequent eicosanoid production is a key mechanism by which a
      Mediterranean diet can exert anti-inflammatory effects. Both dietary fatty acids
      and fatty acid metabolism determine fatty acid availability for cyclooxygenase-
      and lipoxygenase-dependent production of eicosanoids, namely prostaglandins and
      leukotrienes. In dietary intervention studies and in observational studies of the
      Mediterranean diet, blood levels of fatty acids do reflect dietary intakes but
      are attenuated. Small differences in fatty acid levels, however, appear to be
      important, especially when exposures occur over long periods of time. This review
      summarizes how fat intakes from a Greek-style Mediterranean diet can be expected
      to affect fatty acid metabolizing proteins, with an emphasis on the metabolic
      pathways that lead to the formation of proinflammatory eicosanoids. The proteins
      involved in these pathways are ripe for investigation using proteomic approaches
      and may be targets for colon cancer prevention.

PMID- 22133203
TI  - Heightened inflammasome activation is linked to age-related cognitive impairment
      in Fischer 344 rats.
AB  - BACKGROUND: Members of the mammalian nucleotide binding domain, leucine-rich
      repeat (LRR)-containing receptor (NLR) family of proteins are key modulators of
      innate immunity regulating inflammation. Our previous work has shown that among
      the members of this family, NLRP1/NALP1, present in neurons, plays a crucial role
      in inflammasome formation and the production of the inflammatory cytokines
      interleukin (IL) -1beta and IL-18 after various types of central nervous system
      injury. RESULTS: We investigated whether age-related cognitive decline may
      involve a heightened inflammatory response associated with activation of the
      NLRP1 inflammasome in the hippocampus. Young (3 months) and aged (18 months) male
      Fischer 344 rats were tested in a spatial acquisition task via Morris water maze.
      Following behavioral testing, hippocampal lysates were assayed for expression of
      NLRP1 inflammasome components and inflammatory cytokines. Hippocampal lysates
      from aged rats showed significantly higher levels of NLRP1 inflammasome
      constituents, caspase-1, caspase-11, the purinergic receptor P2X7, pannexin-1 and
      X-linked inhibitor of apoptosis (XIAP) than lysates from younger animals.
      Following treatment with probenecid, an inhibitor or pannexin-1, aged animals
      demonstrated reduction in inflammasome activation and improvement in spatial
      learning performance. CONCLUSIONS: Our behavioral findings are consistent with
      increases in IL-1beta and IL-18 that have been previously shown to correlate with
      spatial learning deficits. Probenecid reduced activated caspase-1 and ameliorated
      spatial learning deficits in aged rats. Thus, aging processes stimulate
      activation of the NLRP1 inflammasome and secretion of IL-1beta and IL-18 that may
      contribute to age-related cognitive decline in the growing elderly population.
      Moreover, probenecid may be potentially useful as a therapy to improve cognitive
      outcomes in the aging population.

PMID- 22133204
TI  - Recommendations for avoiding knee pain after intramedullary nailing of tibial
      shaft fractures.
AB  - BACKGROUND: The objective of this study is to analyze the proximal tibiofibular
      joint in patients with knee pain after treatment of tibial shaft fractures with
      locked intramedullary nail. FINDINGS: The proximal tibiofibular joint was
      analyzed in 30 patients, who reported knee pain after tibial nailing, and
      standard radiograph and computed tomography were performed to examine the
      proximal third of the tibia. Twenty patients (68.9%) presented the proximal screw
      crossing the proximal tibiofibular joint and 13 (44.8%) had already removed the
      nail and/or screw. Four patients (13.7%) reported complaint of knee pain.
      However, the screw did not reach the proximal tibiofibular joint. Five patients
      (17.2%) complained of knee pain although the screw toward the joint did not
      affect the proximal tibiofibular joint. CONCLUSION: When using nails with oblique
      proximal lock, surgeons should be careful not to cause injury in the proximal
      tibiofibular joint, what may be one of the causes of knee pain. Thus, the authors
      suggest postoperative evaluation performing computed tomography when there is
      complaint of pain.

PMID- 22133205
TI  - Allelic variant of NOS1AP effects on cardiac alternans of repolarization during
      exercise testing.
AB  - INTRODUCTION: A repolarization abnormality manifested as T-wave alternans (TWA)
      in electrocardiogram (ECG) predicts cardiovascular mortality. A common variant in
      the NOS1AP gene is associated with mortality and QT interval duration, possibly
      in a gender-specific manner, but data is lacking on potential association with
      TWA. This study tested association between rs10494366 in NOS1AP and both TWA and
      4-year mortality. MATERIAL AND METHODS: A total of 1963 Finnish Cardiovascular
      Study participants (36.6% female, 57.1 +/- 13.0 years) were genotyped and their
      maximal TWA values were measured from continuous ECG recordings during clinical
      exercise test at rest, exercise and recovery. RESULTS: We observed a significant
      gender-specific effect of NOS1AP genotype on TWA. In all subjects, there was no
      statistically significant difference between the three genotypes (TT, TG, GG) in
      the responses of TWA over the entire exercise test (time-by-genotype interaction
      p = 0.057). In women, after adjustment for age, coronary heart disease and beta
      blocker medication status, changes of TWA over different phases of exercise test
      were significantly associated with NOS1AP genotype (time-by-genotype interaction
      p = 0.001). In men, NOS1AP rs10494366 was not associated with TWA. During follow
      up (mean 47 months), 113 patients died. NOS1AP rs10494366 was not a statistically
      significant predictor of mortality. CONCLUSION: The NOSIAP variant rs10494366
      influences TWA and TWA response during clinical exercise test in females. Gender
      specific effects have also been previously reported for the influence of the
      variant on QT interval. If replicated, these findings should prompt studies to
      further elucidate the mechanisms underlying the gender differences in NOS1AP
      effects on repolarization.

PMID- 22133206
TI  - Acute hyperinsulinemia is followed by increased serum concentrations of
      fibroblast growth factor 23 in type 2 diabetes patients.
AB  - BACKGROUND: Phosphate homeostasis is connected to glucose metabolism and is
      influenced by insulin, but the role of fibroblast growth factor 23 (FGF23) is
      unknown in this relation. Therefore, the levels of FGF23 and phosphate were
      investigated during a euglycemic-hyperinsulinemic clamp in healthy and type 2
      diabetic individuals. METHODS: The study population consisted of ten type 2
      diabetic patients, ten weight-matched glucose-tolerant obese subjects, and ten
      healthy lean subjects. All subjects underwent a 4-h euglycemic-hyperinsulinemic
      clamp using physiological hyperinsulinemia (40 mU/min per m(2)) to determine
      glucose disposal rates. Blood samples for measurement of serum FGF23 and insulin,
      plasma phosphate and glucose, and HbA(1c) were drawn before and after insulin
      infusion. RESULTS: The three groups did not differ in baseline levels of serum
      FGF23. Insulin infusion increased serum FGF23 in the diabetic group (p = 0.009),
      but not in the other groups. The increase in serum FGF23 correlated strongly with
      increase in insulin levels in the diabetic group (r = 0.83; p = 0.003). In the
      overall group insulin infusion suppressed plasma phosphate concentrations (p =
      0.006), but with no differences between the groups. CONCLUSIONS: Physiological
      hyperinsulinemia is under euglycemic conditions followed by a significant
      increase in serum FGF23 concentrations in diabetic individuals, which correlated
      with change in insulin level. The interplay between insulin effects and FGF23 may
      be important for the understanding of phosphate metabolism in relation to type 2
      diabetes and its vascular complications.

PMID- 22133207
TI  - Elderly cases of Churg-Strauss syndrome: case report and review of Japanese
      cases.
AB  - Churg-Strauss syndrome (CSS) is a vasculitis usually thought to affect
      comparatively young individuals, however, elderly cases of CSS are being reported
      increasingly. We report two elderly cases of CSS and review 123 cases of CSS
      reported in Japan between 2003 and 2010. The two patients showed typical features
      of CSS such as asthma, chronic sinusitis, purpura and mononeuritis multiplex. The
      biopsy specimens demonstrated leukocytoclastic vasculitis with infiltration of
      eosinophils. Both patients responded well to oral prednisolone. The age of the
      CSS cases we reviewed ranged from the teens to the 80s, with 47.2% of the
      patients aged 60 years or older. These patients tended more frequently to have
      complications such as gastrointestinal involvement, and a higher mortality rate.
      Elderly cases of CSS are not rare. Correct diagnosis at an earlier stage and
      careful, long-term follow up are of particular importance in preventing a fatal
      outcome.

PMID- 22133208
TI  - Budesonide/formoterol pressurized metered-dose inhaler versus budesonide: a
      randomized controlled trial in black patients with asthma.
AB  - OBJECTIVE: Concerns exist that responses to long-acting beta(2)-adrenergic
      agonists in black patients may differ from the general population. The efficacy
      and safety of budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler
      (pMDI) versus budesonide dry powder inhaler (BUD DPI) were evaluated in
      adolescent and adult black asthma patients. METHODS: This 12-week, randomized,
      double-blind, multicenter, phase IV US study was conducted in 311 self-reported
      black patients aged >=12 years with moderate to severe persistent asthma,
      previously receiving medium- to high-dose inhaled corticosteroid. After 2 weeks
      on BUD 90 MUg * 2 inhalations twice daily (bid), symptomatic patients were
      randomized to BUD/FM 160/4.5 MUg * 2 inhalations bid or BUD 180 MUg * 2
      inhalations bid. RESULTS: Improvement in predose forced expiratory volume in 1
      second from baseline to the treatment mean (primary variable) was greater with
      BUD/FM versus BUD (0.16 vs. 0.07 L; p = .008); this effect was also observed at
      weeks 2, 6, and end of treatment (p <= .032). Greater improvements (p < .001) in
      peak expiratory flow with BUD/FM versus BUD were seen at first measurement and
      maintained during 12 weeks (morning: 25.34 vs. 7.53 L/minute, respectively;
      evening: 21.61 vs. 7.67 L/minute, respectively); greater improvements in daily
      asthma symptom score and rescue medication use were also observed (p <= .039).
      Both treatments were well tolerated, with similar safety profiles. CONCLUSIONS:
      In this population of black asthma patients, BUD/FM pMDI resulted in greater
      improvements in pulmonary function and asthma control versus BUD DPI, with
      similar safety profiles.

PMID- 22133209
TI  - Striving to promote male involvement in maternal health care in rural and urban
      settings in Malawi - a qualitative study.
AB  - BACKGROUND: Understanding the strategies that health care providers employ in
      order to invite men to participate in maternal health care is very vital
      especially in today's dynamic cultural environment. Effective utilization of such
      strategies is dependent on uncovering the salient issues that facilitate male
      participation in maternal health care. This paper examines and describes the
      strategies that were used by different health care facilities to invite husbands
      to participate in maternal health care in rural and urban settings of southern
      Malawi. METHODS: The data was collected through in-depth interviews from sixteen
      of the twenty health care providers from five different health facilities in
      rural and urban settings of Malawi. The health facilities comprised two health
      centres, one district hospital, one mission hospital, one private hospital and
      one central hospital. A semi-structured interview guide was used to collect data
      from health care providers with the aim of understanding strategies they used to
      invite men to participate in maternal health care. RESULTS: Four main strategies
      were used to invite men to participate in maternal health care. The strategies
      were; health care provider initiative, partner notification, couple initiative
      and community mobilization. The health care provider initiative and partner
      notification were at health facility level, while the couple initiative was at
      family level and community mobilization was at village (community) level. The
      community mobilization had three sub-themes namely; male peer initiative, use of
      incentives and community sensitization. The sustainability of each strategy to
      significantly influence behaviour change for male participation in maternal
      health care is discussed. CONCLUSION: Strategies to invite men to participate in
      maternal health care were at health facility, family and community levels. The
      couple strategy was most appropriate but was mostly used by educated and city
      residents. The male peer strategy was effective and sustainable at community
      level. There is need for creation of awareness in men so that they sustain their
      participation in maternal health care activities of their female partners even in
      the absence of incentives, coercion or invitation.

PMID- 22133210
TI  - Analysis of inbreeding depression in mixed-mating plants provides evidence for
      selective interference and stable mixed mating.
AB  - Hermaphroditic individuals can produce both selfed and outcrossed progeny, termed
      mixed mating. General theory predicts that mixed-mating populations should evolve
      quickly toward high rates of selfing, driven by rapid purging of genetic load and
      loss of inbreeding depression (ID), but the substantial number of mixed-mating
      species observed in nature calls this prediction into question. Lower average ID
      reported for selfing than for outcrossing populations is consistent with purging
      and suggests that mixed-mating taxa in evolutionary transition will have
      intermediate ID. We compared the magnitude of ID from published estimates for
      highly selfing (r > 0.8), mixed-mating (0.2 <= r >= 0.8), and highly outcrossing
      (r < 0.2) plant populations across 58 species. We found that mixed-mating and
      outcrossing taxa have equally high average lifetime ID (delta= 0.58 and 0.54,
      respectively) and similar ID at each of four life-cycle stages. These results are
      not consistent with evolution toward selfing in most mixed-mating taxa. We
      suggest that prevention of purging by selective interference could explain stable
      mixed mating in many natural populations. We identify critical gaps in the
      empirical data on ID and outline key approaches to filling them.

PMID- 22133212
TI  - Does local adaptation cause high population differentiation of Silene latifolia Y
      chromosomes?
AB  - Natural selection can reduce the effective population size of the nonrecombining
      Y chromosome, whereas local adaptation of Y-linked genes can increase the
      population divergence and overall intra-species polymorphism of Y-linked
      sequences. The plant Silene latifolia evolved a Y chromosome relatively recently,
      and most known X-linked genes have functional Y homologues, making the species
      interesting for comparisons of X- and Y-linked diversity and subdivision. Y
      linked genes show higher population differentiation, compared to X-linked genes,
      and this might be maintained by local adaptation in Y-linked genes (or low
      sequence diversity). Here we attempt to test between these causes by
      investigating DNA polymorphism and population differentiation using a larger set
      of Y-linked and X-linked S. latifolia genes (than used previously), and show that
      net sequence divergence for Y-linked sequences (measured by D(a) , also known as
      delta) is low, and not consistently higher than X-linked genes. This does not
      support local adaptation, instead, the higher values of differentiation measures
      for the Y-linked genes probably result largely from reduced total variation on
      the Y chromosome, which in turn reflect deterministic processes lowering
      effective population sizes of evolving Y-chromosomes.

PMID- 22133211
TI  - Social dilemmas among supergenes: intragenomic sexual conflict and a selfing
      solution in Oenothera.
AB  - Recombination is a powerful policing mechanism to control intragenomic cheats.
      The "parliament of the genes" can often rapidly block driving genes from cheating
      during meiosis. But what if the genome parliament is reduced to only two members,
      or supergenes? Using a series of simple game-theoretic models inspired by the
      peculiar genetics of Oenothera sp., we illustrate that a two supergene genome
      (alpha and beta) can produce a number of surprising evolutionary dynamics,
      including increases in lineage longevity following a transition from sexuality
      (outcrossing) to asexuality (clonal self-fertilization). We end by interpreting
      the model in the broader context of the evolution of mutualism, which highlights
      that greater alpha, beta cooperation in the self-fertilizing model can be viewed
      as an example of partner fidelity driving multilineage cooperation.

PMID- 22133213
TI  - Population genomic tests of models of adaptive radiation in Lake Victoria region
      cichlid fish.
AB  - Adaptive radiation is usually thought to be associated with speciation, but the
      evolution of intraspecific polymorphisms without speciation is also possible. The
      radiation of cichlid fish in Lake Victoria (LV) is perhaps the most impressive
      example of a recent rapid adaptive radiation, with 600+ very young species. Key
      questions about its origin remain poorly characterized, such as the importance of
      speciation versus polymorphism, whether species persist on evolutionary time
      scales, and if speciation happens more commonly in small isolated or in large
      connected populations. We used 320 individuals from 105 putative species from
      Lakes Victoria, Edward, Kivu, Albert, Nabugabo and Saka, in a radiation-wide
      amplified fragment length polymorphism (AFLP) genome scan to address some of
      these questions. We demonstrate pervasive signatures of speciation supporting the
      classical model of adaptive radiation associated with speciation. A positive
      relationship between the age of lakes and the average genomic differentiation of
      their species, and a significant fraction of molecular variance explained by
      above-species level taxonomy suggest the persistence of species on evolutionary
      time scales, with radiation through sequential speciation rather than a single
      starburst. Finally the large gene diversity retained from colonization to
      individual species in every radiation suggests large effective population sizes
      and makes speciation in small geographical isolates unlikely.

PMID- 22133214
TI  - Testing for differences in rates of speciation, extinction, and morphological
      evolution in four tribes of cichlids endemic to Lake Tanganyika, East Africa.
AB  - Patterns of morphological disparity yield important insight into the causes of
      diversification and adaptive radiation in East African cichlids. However,
      comparisons of cichlid disparity have often failed to consider the effects that
      differing clade ages or stochasticity may have on disparity before making
      interpretations. Here, a model of branching morphological evolution allows
      assessment of the relative contributions of differing turnover and morphological
      change rates, clade ages, and stochastic variation to the observed patterns of
      disparity in four endemic tribes of Lake Tanganyika cichlids. Simulations compare
      the likelihood of generating the observed disparity of the four tribes using 200
      parameter combinations and four model conditioning variations, which allows
      inference of evolutionary rate differences among clades. The model is generally
      robust to model conditioning, the approach to data analysis, and model
      assumptions. Disparity differences among the first three cichlid tribes,
      Ectodini, Lamprologini, and Tropheini, can be explained entirely by stochasticity
      and age, whereas the fourth tribe, Cyprichromini, has likely experienced lower
      rates of turnover and morphological change. This rate difference is likely
      related to the low dietary diversity of the Cyprichromini. These results
      highlight the importance of considering both clade age and stochastic variation
      when interpreting morphological diversity and evolutionary processes.

PMID- 22133215
TI  - Within-population structure highlighted by differential introgression across
      semipermeable barriers to gene flow in Anguilla marmorata.
AB  - In the marine environment, differential gene exchange between partially
      reproductively isolated taxa can result in introgression that extends over long
      distances due to high larval dispersal potential. However, the degree to which
      this process contributes to interlocus variance of genetic differentiation within
      introgressed populations remains unclear. Using a genome-scan approach in the
      Indo-Pacific eel Anguilla marmorata, we investigated the degree of
      interpopulation genetic differentiation, the rate of introgression, and within
      population genetic patterns at 858 AFLP markers genotyped in 1117 individuals.
      Three divergent populations were identified based on clustering analysis. Genetic
      assignments of individuals revealed the existence of different types of hybrids
      that tended to co-occur with parental genotypes in three population contact
      zones. Highly variable levels of genetic differentiation were found between
      populations across the AFLP markers, and reduced rates of introgression were
      shown at some highly differentiated loci. Gene flow across semipermeable genetic
      barriers was shown to generate spatial introgression patterns at some loci which
      define within-population structure over long distances. These results suggest
      that differential introgression in subdivided populations may be relevant when
      interpreting spatial variation patterns displayed by outlying loci in other
      marine fish populations.

PMID- 22133216
TI  - The quantitative genetics of incipient speciation: heritability and genetic
      correlations of skeletal traits in populations of diverging Favia fragum
      ecomorphs.
AB  - Recent speciation events provide potential opportunities to understand the
      microevolution of reproductive isolation. We used a marker-based approach and a
      common garden to estimate the additive genetic variation in skeletal traits in a
      system of two ecomorphs within the coral species Favia fragum: a Tall ecomorph
      that is a seagrass specialist, and a Short ecomorph that is most abundant on
      coral reefs. Considering both ecomorphs, we found significant narrow-sense
      heritability (h(2) ) in a suite of measurements that define corallite
      architecture, and could partition additive and nonadditive variation for some
      traits. We found positive genetic correlations for homologous height and length
      measurements among different types of vertical plates (costosepta) within
      corallites, but negative correlations between height and length within, as well
      as between costosepta. Within ecomorphs, h(2) estimates were generally lower,
      compared to the combined ecomorph analysis. Marker-based estimates of h(2) were
      comparable to broad-sense heritability (H) obtained from parent-offspring
      regressions in a common garden for most traits, and similar genetic co-variance
      matrices for common garden and wild populations may indicate relatively small G *
      E interactions. The patterns of additive genetic variation in this system invite
      hypotheses of divergent selection or genetic drift as potential evolutionary
      drivers of reproductive isolation.

PMID- 22133217
TI  - Bridging scales in the evolution of infectious disease life histories: theory.
AB  - A significant goal of recent theoretical research on pathogen evolution has been
      to develop theory that bridges within- and between-host dynamics. The main
      approach used to date is one that nests within-host models of pathogen
      replication in models for the between-host spread of infectious diseases.
      Although this provides an elegant approach, it nevertheless suffers from some
      practical difficulties. In particular, the information required to satisfactorily
      model the mechanistic details of the within-host dynamics is not often available.
      Here, we present a theoretical approach that circumvents these difficulties by
      quantifying the relevant within-host factors in an empirically tractable way. The
      approach is closely related to quantitative genetic models for function-valued
      traits, and it also allows for the prediction of general characteristics of
      disease life history, including the timing of virulence, transmission, and host
      recovery. In a companion paper, we illustrate the approach by applying it to data
      from a model system of malaria.

PMID- 22133218
TI  - Reverse evolution: selection against costly resistance in disease-free microcosm
      populations of Paramecium caudatum.
AB  - Evolutionary costs of parasite resistance arise if genes conferring resistance
      reduce fitness in the absence of parasites. Thus, parasite-mediated selection may
      lead to increased resistance and a correlated decrease in fitness, whereas
      relaxed parasite-mediated selection may lead to reverse evolution of increased
      fitness and a correlated decrease in resistance. We tested this idea in
      experimental populations of the protozoan Paramecium caudatum and the parasitic
      bacterium Holospora undulata. After eight years, resistance to infection and
      asexual reproduction were compared among paramecia from (1) "infected"
      populations, (2) uninfected "naive" populations, and (3) previously infected,
      parasite-free "recovered" populations. Paramecia from "infected" populations were
      more resistant (+12%), but had lower reproduction (-15%) than "naive" paramecia,
      indicating an evolutionary trade-off between resistance and fitness. Recovered
      populations showed similar reproduction to naive populations; however, resistance
      of recently (<3 years) recovered populations was similar to paramecia from
      infected populations, whereas longer (>3 years) recovered populations were as
      susceptible as naive populations. This suggests a weak, convex trade-off between
      resistance and fitness, allowing recovery of fitness, without complete loss of
      resistance, favoring the maintenance of a generalist strategy of intermediate
      fitness and resistance. Our results indicate that (co)evolution with parasites
      can leave a genetic signature in disease-free populations.

PMID- 22133219
TI  - Competence increases survival during stress in Streptococcus pneumoniae.
AB  - Horizontal gene transfer mediated by transformation is of central importance in
      bacterial evolution. However, numerous questions remain about the maintenance of
      processes that underlie transformation. Most hypotheses for the benefits of
      transformation focus on what bacteria might do with DNA, but ignore the important
      fact that transformation is subsumed within the broader process of competence.
      Accordingly, the apparent benefits of transformation might rely less on
      recombination than on other potential benefits associated with the broader suite
      of traits regulated by competence. We examined the importance of this distinction
      in the naturally competent species Streptococcus pneumoniae, focusing
      specifically on predictions of the DNA-for-repair hypothesis. We confirm earlier
      results in other naturally competent species that transformation protects against
      DNA-damaging stress. In addition, we show that the stress-protection extends to
      non-DNA-damaging stress. More important, we find that for some forms of stress
      transformation is not required for cells to benefit from the induction of
      competence. This rejects the narrowly defined DNA-for-repair hypotheses and
      provides the first support for Claverys' hypothesis that competence, but not
      necessarily transformation, may act as a general process to relieve stress. Our
      results highlight the need to distinguish benefits of transformation from broader
      benefits of competence that do not rely on DNA uptake and recombination.

PMID- 22133220
TI  - Experimental evolution of ultraviolet radiation resistance in Escherichia coli.
AB  - Ultraviolet (UV) light is a major cause of stress, mutation, and mortality in
      microorganisms, causing numerous forms of cellular damage. Nevertheless, there is
      tremendous variation within and among bacterial species in their sensitivity to
      UV light. We investigated direct and correlated responses to selection during
      exposure to UV. Replicate lines of Escherichia coli K12 were propagated for 600
      generations, half with UV and half as a control without UV. All lines responded
      to selection, and we found strong positive and negative correlated responses to
      selection associated with increased UV resistance. Compared to Control
      populations, UV-selected populations increased in desiccation and starvation
      resistance approximately twofold but were 10 times more sensitive to
      hypersalinity. There was little evidence for a persistent large competitive
      fitness cost to UV resistance. These results suggest that natural variation in UV
      resistance may be maintained by trade-offs for resistance to other abiotic
      sources of mortality. We observed an average twofold increase in cell size by the
      UV-selected populations, consistent with a structural mode of adaptation to UV
      exposure having preadaptive and maladaptive consequences to other abiotic
      stresses.

PMID- 22133221
TI  - A tight balance between natural selection and gene flow in a southern African
      arid-zone endemic bird.
AB  - Gene flow is traditionally thought to be antagonistic to population
      differentiation and local adaptation. However, recent studies have demonstrated
      that local adaptation can proceed provided that selection is greater than the
      homogenizing effects of gene flow. We extend these initial studies by combining
      ecology (climate), phenotype (body size), physiological genetics (oxidative
      phosphorylation genes), and neutral loci (nuclear microsatellites and introns) to
      test whether selection can counter-balance gene flow and hence promote local
      adaptation in a bird whose distribution spans an aridity gradient. Our results
      show that the Karoo scrub-robin's climatic niche is spatially structured,
      providing the potential for local adaptation to develop. We found remarkably
      discordant patterns of divergence among mtDNA, morphology, and neutral loci. For
      the mitochondrial genes, two amino acid replacements, strong population structure
      and reduced gene flow were associated with the environmental gradient separating
      western coastal sites from the interior of southern Africa. In contrast,
      morphology and the neutral loci exhibited variation independent of environmental
      variables, and revealed extensive levels of gene flow across the aridity
      gradient, 50 times larger than the estimates for mitochondrial genes. Together,
      our results suggest that selective pressures on physiology, mediated by the
      mitochondrial genome, may well be a common mechanism for facilitating local
      adaptation to new climatic conditions.

PMID- 22133222
TI  - Catch me if you can--predation affects divergence in a polyphenic species.
AB  - Predation is a major driving force in evolution. Predation has been shown to
      select for size, morphology, and camouflage. Many animals use camouflage to
      reduce predation risk. In some cases, individuals can adjust their pigmentation,
      enabling them a higher survival in a heterogeneous environment. Here, we show
      that the difference in pigmentation between juvenile perch individuals (Perca
      fluvuiatilis) occupying different environments (open water and vegetated habitats
      of lakes) is likely a consequence of predator selection. Lightly pigmented
      individuals have a higher chance of survival in open water whereas darker
      pigmented individuals survive better in vegetation. As a response to predators,
      individuals forced into the vegetation by predators developed darker skin whereas
      the skin of individuals forced into open water became lighter. In a common garden
      experiment, in the absence of predation, we found that pigmentation in juvenile
      perch is only due to plasticity and not to genetic variation. However, contrary
      to predictions, individuals raised in open water developed darker skin compared
      to individuals raised in vegetation. This may be a response to UV-stress.
      Overall, our results suggest that predation can be a strong selective agent on
      pigmentation differences among conspecifics occupying different habitats.

PMID- 22133223
TI  - The geographic structure of selection on a coevolving interaction between social
      parasitic wasps and their hosts hampers social evolution.
AB  - Social parasites exploit societies, rather than organisms, and rear their brood
      in social insect colonies at the expense of their hosts, triggering a
      coevolutionary process that may affect host social structure. The resulting
      coevolutionary trajectories may be further altered by selection imposed by
      predators, which exploit the abundant resources concentrated in these nests.
      Here, we show that geographic differences in selection imposed by predators
      affects the structure of selection on coevolving hosts and their social
      parasites. In a multiyear study, we monitored the fate of the annual breeding
      attempts of the solitary nesting foundresses of Polistes biglumis wasps in four
      geographically distinct populations that varied in levels of attack by the
      congeneric social parasite, P. atrimandibularis. Foundress fitness depended
      mostly on whether, during the long founding phase, a colony was invaded by social
      parasites or attacked by predators. Foundresses from each population differed in
      morphological traits and reproductive tactics that were consistent with selection
      imposed by their natural enemies and in ways that may affect host sociality. In
      turn, parasite traits were consistent with selection imposed locally by hosts,
      implying a geographic mosaic of coevolution in this brood parasitic interaction.

PMID- 22133224
TI  - Natural selection on gall size: variable contributions of individual host plants
      to population-wide patterns.
AB  - Studies that provide estimates of the form and magnitude of selection on
      herbivore traits at the level of individual plants in natural populations
      represent a vital step in understanding the interaction of selection and gene
      flow among host-affiliated insect populations when individual plants equate to
      differing selective regimes. We analyzed phenotypic selection on the trait gall
      size for a host-specific gall former at both the individual host plant and
      population level (across host plants) in each of two years. Linear and nonlinear
      selection and the fitness function relating gall size to the probability of
      survivorship in the absence of natural enemies were estimated for each level and
      year. Selection imposed by the host plant was observed in 19 of the 22
      subpopulations monitored. At the population level, linear and nonlinear selection
      were evident each year. However, population-level estimates masked the
      significant heterogeneity in the form and direction of selection evident among
      plants each year. Heterogeneity among gall-former subpopulations is emphasized by
      our findings that selection varied from directional to stabilizing among plants
      and the majority of selection gradients estimated for individual plants did not
      fall within the 95% CIs of the population-level estimates.

PMID- 22133225
TI  - Artificial selection reveals heritable variation for developmental instability.
AB  - Fluctuating (nondirectional) asymmetry (FA) of bilaterally paired structures on a
      symmetrical organism is commonly used to assay the developmental instability (DI)
      caused by environmental or genetic factors. Although evidence for natural
      selection to reduce FA has been reported, evidence that FA (and by extension DI)
      is heritable is weak. We report the use of artificial selection to demonstrate
      heritable variation in the fluctuating asymmetry of interlandmark distances
      within the wing in an outbred population of Drosophila melanogaster. Our
      estimates for the heritability of FA range from 0% to 1% and result in estimates
      for the heritability of DI as large as 20%, comparable to values typical for life
      history traits. These values indicate the existence of evolutionarily relevant
      genetic variation for DI and the effectiveness of selection for reduced FA
      suggests that natural selection has not fixed all the genetic variants that would
      improve developmental stability in these populations.

PMID- 22133226
TI  - Deficiency mapping of the genomic regions associated with effects on
      developmental stability in Drosophila melanogaster.
AB  - Developmental stability is the tendency of morphological traits to resist the
      effects of developmental noise, and is commonly evaluated by examining
      fluctuating asymmetry (FA)-random deviations from perfect bilateral symmetry.
      Molecular mechanisms that control FA have been a long-standing topic of debate in
      the field of evolutionary biology and quantitative genetics. In this study, we
      mapped genomic regions associated with effects on the mean and FA of
      morphological traits, and characterized the trait specificity of those regions. A
      collection of isogenic deficiency strains established by the DrosDel project was
      used for deficiency mapping of genome regions associated with effects on FA. We
      screened 435 genome deficiencies or approximately 64.9% of the entire genome of
      Drosophila melanogaster to map the region that demonstrated a significant effect
      on FA of morphological traits. We found that 406 deficiencies significantly
      affected the mean of morphological traits, and 92 deficiencies increased FA.
      These results suggest that several genomic regions have the potential to affect
      developmental stability. They also suggest the possibility of the existence of
      trait-specific and trait-nonspecific mechanisms for stabilizing developmental
      processes. The new findings in this study could provide insight into the
      understanding of the genetic architecture underlying developmental stability.

PMID- 22133227
TI  - A novel comparative method for identifying shifts in the rate of character
      evolution on trees.
AB  - Evolutionary biologists since Darwin have been fascinated by differences in the
      rate of trait-evolutionary change across lineages. Despite this continued
      interest, we still lack methods for identifying shifts in evolutionary rates on
      the growing tree of life while accommodating uncertainty in the evolutionary
      process. Here we introduce a Bayesian approach for identifying complex patterns
      in the evolution of continuous traits. The method (auteur) uses reversible-jump
      Markov chain Monte Carlo sampling to more fully characterize the complexity of
      trait evolution, considering models that range in complexity from those with a
      single global rate to potentially ones in which each branch in the tree has its
      own independent rate. This newly introduced approach performs well in recovering
      simulated rate shifts and simulated rates for datasets nearing the size typical
      for comparative phylogenetic study (i.e., >=64 tips). Analysis of two large
      empirical datasets of vertebrate body size reveal overwhelming support for
      multiple-rate models of evolution, and we observe exceptionally high rates of
      body-size evolution in a group of emydid turtles relative to their evolutionary
      background. auteur will facilitate identification of exceptional evolutionary
      dynamics, essential to the study of both adaptive radiation and stasis.

PMID- 22133228
TI  - Latitudinal and climatic variation in body size and dorsal scale counts in
      Sceloporus lizards:a phylogenetic perspective.
AB  - Squamates often follow an inverse Bergmann's rule, with larger-bodied animals
      occurring in warmer areas or at lower latitudes. The size of dorsal scales in
      lizards has also been proposed to vary along climatic gradients, with species in
      warmer areas exhibiting larger scales, putatively to reduce heat load. We tested
      for these patterns in the diverse and widespread lizard genus Sceloporus. Among
      106 species or populations, body size was associated positively with maximum
      temperature (consistent with the inverse of Bergmann's rule) and aridity, but did
      not covary with latitude. Scale size (inferred from the inverse relation with
      numbers of scales) was positively related to body size. Controlling for body size
      via multiple regression, scale size was associated negatively with latitude (best
      predictor), positively with minimum temperature, and negatively with aridity
      (similar results were obtained using scores from a principal components analysis
      of latitude and climatic indicators). Thus, lizards with larger scales are not
      necessarily found in areas with higher temperatures. Univariate analyses
      indicated phylogenetic signal for body size, scale counts, latitude, and all
      climate indicators. In all cases, phylogenetic regression models fit the data
      significantly better than nonphylogenetic models; thus, residuals for log(10)
      number of dorsal scale rows exhibited phylogenetic signal.

PMID- 22133229
TI  - Convergent evolution of phenotypic integration and its alignment with
      morphological diversification in Caribbean Anolis ecomorphs.
AB  - The adaptive landscape and the G-matrix are keys concepts for understanding how
      quantitative characters evolve during adaptive radiation. In particular, whether
      the adaptive landscape can drive convergence of phenotypic integration (i.e., the
      pattern of phenotypic variation and covariation summarized in the P-matrix) is
      not well studied. We estimated and compared P for 19 morphological traits in
      eight species of Caribbean Anolis lizards, finding that similarity in P among
      species was not correlated with phylogenetic distance. However, greater
      similarity in P among ecologically similar Anolis species (i.e., the trunk-ground
      ecomorph) suggests the role of convergent natural selection. Despite this
      convergence and relatively deep phylogenetic divergence, a large portion of
      eigenstructure of P is retained among our eight focal species. We also analyzed P
      as an approximation of G to test for correspondence with the pattern of
      phenotypic divergence in 21 Caribbean Anolis species. These patterns of
      covariation were coincident, suggesting that either genetic constraint has
      influenced the pattern of among-species divergence or, alternatively, that the
      adaptive landscape has influenced both G and the pattern of phenotypic divergence
      among species. We provide evidence for convergent evolution of phenotypic
      integration for one class of Anolis ecomorph, revealing yet another important
      dimension of evolutionary convergence in this group.

PMID- 22133231
TI  - The transmission-virulence trade-off and superinfection: comments to Smith.

PMID- 22133230
TI  - Negative epistasis between alpha+ thalassaemia and sickle cell trait can explain
      interpopulation variation in South Asia.
AB  - Recent studies in Kenya and Ghana have shown that individuals who inherit two
      malaria-protective genetic disorders of haemoglobin-alpha(+) thalassaemia and
      sickle cell trait-experience a much lower level of malaria protection than those
      who inherit sickle cell trait alone. We have previously demonstrated that this
      can limit the frequency of alpha(+) thalassaemia in a population in which sickle
      cell is present, which may account for the frequency of alpha(+) thalassaemia in
      sub-Saharan Africa not exceeding 50%. Here we consider the relationship between
      alpha(+) thalassaemia and sickle cell in South Asian populations, and show that
      very high levels of alpha(+) thalassaemia combined with varying levels of malaria
      selection can explain why sickle cell has penetrated certain South Asian
      populations but not others.

PMID- 22133233
TI  - Components representation of negative numbers: evidence from auditory stimuli
      detection and number classification tasks.
AB  - Past research suggested that negative numbers could be represented in terms of
      their components in the visual modality. The present study examined the
      processing of negative numbers in the auditory modality and whether it is
      affected by context. Experiment 1 employed a stimuli detection task where only
      negative numbers were presented binaurally. Experiment 2 employed the same task,
      but both positive and negative numbers were mixed as cues. A reverse attentional
      spatial-numerical association of response codes (SNARC) effect for negative
      numbers was obtained in these two experiments. Experiment 3 employed a number
      classification task where only negative numbers were presented binaurally.
      Experiment 4 employed the same task, but both positive and negative numbers were
      mixed. A reverse SNARC effect for negative numbers was obtained in these two
      experiments. These findings suggest that negative numbers in the auditory
      modality are generated from the set of positive numbers, thus supporting a
      components representation.

PMID- 22133234
TI  - A structured approach to improving patient safety: Lessons from a public safety
      net system.

PMID- 22133235
TI  - Teen dental plan voucher use.

PMID- 22133236
TI  - Poultry as a host for the zoonotic pathogen Campylobacter jejuni.
AB  - Campylobacteriosis is the most reported foodborne gastroenteritic disease and
      poses a serious health burden in industrialized countries. Disease in humans is
      mainly caused by the zoonotic pathogen Campylobacter jejuni. Due to its wide
      spread occurrence in the environment, the epidemiology of Campylobacter remains
      poorly understood. It is generally accepted, however, that chickens are a natural
      host for Campylobacter jejuni, and for Campylobacter spp. in general, and that
      colonized broiler chicks are the primary vector for transmitting this pathogen to
      humans. Several potential sources and vectors for transmitting C. jejuni to
      broiler flocks have been identified. Initially, one or a few broilers can become
      colonized at an age of >2 weeks until the end of rearing, after which the
      infection will rapidly spread throughout the entire flock. Such a flock is
      generally colonized until slaughter and infected birds carry a very high C.
      jejuni load in their gastrointestinal tract, especially the ceca. This eventually
      results in contaminated carcasses during processing, which can transmit this
      pathogen to humans. Recent genetic typing studies showed that chicken isolates
      can frequently be linked to human clinical cases of Campylobacter enteritis.
      However, despite the increasing evidence that the chicken reservoir is the number
      one risk factor for disease in humans, no effective strategy exists to reduce
      Campylobachter prevalence in poultry flocks, which can in part be explained by
      the incomplete understanding of the epidemiology of C. jejuni in broiler flocks.
      As a result, the number of human campylobacteriosis cases associated with the
      chicken vector remains strikingly high.

PMID- 22133237
TI  - Mesoporous multifunctional upconversion luminescent and magnetic "nanorattle"
      materials for targeted chemotherapy.
AB  - Nanorattles consisting of hydrophilic, rare-earth-doped NaYF(4) shells each
      containing a loose magnetic nanoparticle were fabricated through an ion-exchange
      process. The inner magnetic Fe(3)O(4) nanoparticles are coated with a SiO(2)
      layer to avoid iron leaching in acidic biological environments. This
      multifunctional mesoporous nanostructure with both upconversion luminescent and
      magnetic properties has excellent water dispersibility and a high drug-loading
      capacity. The material emits visible luminescence upon NIR excitation and can be
      directed by an external magnetic field to a specific target, making it an
      attractive system for a variety of biological applications. Measurements on cells
      incubated with the nanorattles show them to have low cytotoxicity and excellent
      cell imaging properties. In vivo experiments yield highly encouraging tumor
      shrinkage with the antitumor drug doxorubicin (DOX) and significantly enhanced
      tumor targeting in the presence of an applied magnetic field.

PMID- 22133238
TI  - Biomimetic mineralization of woven bone-like nanocomposites: role of collagen
      cross-links.
AB  - Ideal biomaterials for bone grafts must be biocompatible, osteoconductive,
      osteoinductive and have appropriate mechanical properties. For this, the
      development of synthetic bone substitutes mimicking natural bone is desirable,
      but this requires controllable mineralization of the collagen matrix. In this
      study, densified collagen films (up to 100 MUm thick) were fabricated by a
      plastic compression technique and cross-linked using carbodiimide. Then, collagen
      hydroxyapatite composites were prepared by using a polymer-induced liquid
      precursor (PILP) mineralization process. Compared to traditional methods that
      produce only extrafibrillar hydroxyapatite (HA) clusters on the surface of
      collagen scaffolds, by using the PILP mineralization process, homogeneous intra-
      and extrafibrillar minerals were achieved on densified collagen films, leading to
      a similar nanostructure as bone, and a woven microstructure analogous to woven
      bone. The role of collagen cross-links on mineralization was examined and it was
      found that the cross-linked collagen films stimulated the mineralization
      reaction, which in turn enhanced the mechanical properties (hardness and
      modulus). The highest value of hardness and elastic modulus was 0.7 +/- 0.1 and
      9.1 +/- 1.4 GPa in the dry state, respectively, which is comparable to that of
      woven bone. In the wet state, the values were much lower (177 +/- 31 and 8 +/- 3
      MPa) due to inherent microporosity in the films, but still comparable to those of
      woven bone in the same conditions. Mineralization of collagen films with
      controllable mineral content and good mechanical properties provide a biomimetic
      route toward the development of bone substitutes for the next generation of
      biomaterials. This work also provides insight into understanding the role of
      collagen fibrils on mineralization.

PMID- 22133239
TI  - Evaluation of a randomized controlled trial in the management of chronic lower
      back pain in a French automotive industry: an observational study.
AB  - OBJECTIVE: To evaluate a specific workplace intervention for the management of
      chronic lower back pain among employees working in assembly positions in the
      automotive industry. DESIGN: Randomized controlled trial. SETTING: On site at the
      workplace of a French automotive manufacturer. PARTICIPANTS: Subjects (N=75
      volunteers) were recruited on site and randomly assigned to either an
      experimental group (n=37) or a control group (n=38). INTERVENTION: The
      experimental group followed a supervised 60-minute session, 3 times per week, of
      muscle strengthening, flexibility, and endurance training during 2 months. The
      control group received no direct intervention. Evaluation took place at baseline,
      2 months, and 6 months. MAIN OUTCOME MEASURES: Pain related parameters were
      evaluated using validated questionnaires and scales translated into French
      (Quebec Back Pain Disability Scale, Rolan Morris Disability Questionnaire, Dallas
      Pain Questionnaire, and the Tampa Scale for Kinesiophobia). Perceived pain
      intensity was evaluated using the numerical rating scale, and physical outcome
      measures were evaluated using specific indicators (flexibility, Biering-Sorensen
      Test, Shirado test). The multivariate analysis of variance, t test, and Wilcoxon
      signed-rank test were used for statistical analysis. RESULTS: We observed a
      significant beneficial effect (P<.025) for the experimental group at 2 and 6
      months in pain parameters, specific flexibility, and in back functions, and a
      significant improvement at 6 months in the control group for the perceived pain
      intensity, anterior flexion, flexibility of quadriceps, and Dallas Pain
      Questionnaire's work recreational score. An increase in the practice of physical
      activity outside the workplace was noted in both groups at 2 months but persisted
      at 6 months for the experimental group. CONCLUSIONS: This study reinforces the
      multiple health benefits of physical activity and physical therapy modalities in
      the workplace by assisting individuals at risk who have chronic LBP.

PMID- 22133240
TI  - Muscle changes following cycling and/or electrical stimulation in pediatric
      spinal cord injury.
AB  - OBJECTIVE: To determine the effect of cycling, electrical stimulation, or both,
      on thigh muscle volume and stimulated muscle strength in children with spinal
      cord injury (SCI). DESIGN: Randomized controlled trial. SETTING: Children's
      hospital specializing in pediatric SCI. PARTICIPANTS: Children (N=30; ages, 5
      13y) with chronic SCI. INTERVENTIONS: Children were randomly assigned to 1 of 3
      interventions: functional electrical stimulation cycling (FESC), passive cycling
      (PC), and noncycling, electrically stimulated exercise (ES). Each group exercised
      for 1 hour, 3 times per week for 6 months at home. MAIN OUTCOME MEASURES:
      Preintervention and postintervention, children underwent magnetic resonance
      imaging to assess muscle volume, and electrically stimulated isometric muscle
      strength testing with the use of a computerized dynamometer. Data were analyzed
      via analyses of covariance (ANCOVA) with baseline measures as covariates. Within
      group changes were assessed via paired t tests. RESULTS: All 30 children
      completed the training. Muscle volume data were complete for 24 children (8 FESC,
      8 PC, 8 ES) and stimulated strength data for 27 children (9 per group). Per
      ANCOVA, there were differences between groups (P<.05) for quadriceps muscle
      volume and stimulated strength, with the ES group having greater changes in
      volume and the FESC group having greater changes in strength. Within-group
      analyses showed increased quadriceps volume and strength for the FESC group and
      increased quadriceps volume for the ES group. CONCLUSIONS: Children receiving
      either electrically stimulated exercise experienced changes in muscle size,
      stimulated strength, or both. These changes may decrease their risk of
      cardiovascular disease, insulin resistance, glucose intolerance, and type 2
      diabetes. CLINICAL TRIALS REGISTRATION NUMBER: NCT00245726.

PMID- 22133241
TI  - Maintenance of aquatic training-induced benefits on mobility and lower-extremity
      muscles among persons with unilateral knee replacement.
AB  - OBJECTIVE: To evaluate the maintenance of observed aquatic training-induced
      benefits at 12-month follow-up. DESIGN: Twelve-month follow-up of a randomized
      controlled study. SETTING: Research laboratory and hospital rehabilitation pool.
      PARTICIPANTS: Population-based sample of 55 to 75-year-old women and men 4 to 18
      months (on average 10mo) after unilateral knee replacement. Fifty people were
      willing to participate in the exercise trial and 42 people in the follow-up
      study. INTERVENTION: Twelve-month follow-up of 12-week progressive aquatic
      resistance training, or no intervention. MAIN OUTCOME MEASURES: Isokinetic knee
      extensor and flexor power, thigh muscle cross-sectional area (CSA), habitual
      walking speed, stair ascending time, and sit-to-stand test. RESULTS: After a 12
      month follow-up, a 32% (95% confidence interval [CI], 10-53) training effect in
      knee extensor power (P=.008) and 50% (95% CI, 9-90) in knee flexor power (P=.005)
      of the operated knee remained. In muscle CSA, the training-induced benefit had
      disappeared at the follow-up. All the significant 12-week improvements in
      habitual walking speed, stair ascending time, and sit-to-stand in the training
      group compared with controls were lost at follow-up. CONCLUSIONS: After the 12
      month follow-up, the 12-week aquatic training-induced benefits in knee extensor
      and flexor power were maintained, whereas the mobility benefits had disappeared.
      Aquatic resistance training should be continued at least on some level to
      maintain the training-induced benefits in mobility.

PMID- 22133242
TI  - Effects of therapeutic gait training using a prosthesis and a treadmill for
      ambulatory patients with hemiparesis.
AB  - OBJECTIVE: To examine the short-term effects of a newly developed hemiparetic
      gait training in which patients walk with a prosthesis applied to the nonparetic
      leg in the flexed knee position. DESIGN: Pre-post nonrandomized controlled trial.
      SETTING: Rehabilitation center and gait laboratory of a university hospital.
      PARTICIPANTS: Community-dwelling ambulatory volunteers (N=22) with chronic
      hemiparesis caused by a unilateral stroke. INTERVENTION: Study subjects
      participated in a gait training program using either a below-knee prosthesis or a
      treadmill. Treadmill gait training was performed at a speed approximating the
      maximum gait velocity for each patient. The 3-week program consisted of a 5
      minute gait training session 2 to 3 times a day. MAIN OUTCOME MEASURES: The
      ground reaction forces, stance time, step length and cadence during walking at a
      comfortable speed, and maximum gait speed, as well as the Berg Balance Score,
      were estimated before and after each training program. RESULTS: In comparison
      with changes after the treadmill gait training, analyses of covariance
      demonstrated a significant increase of the fore-aft ground reaction forces during
      the paretic propulsion phase and a significant increase in the relative durations
      of the paretic and nonparetic single stance involved in a gait cycle after the
      prosthetic gait training (P<.05). CONCLUSIONS: Prosthetic gait training would
      have different effects on a hemiparetic gait than treadmill gait training. The
      gait-related task inducing the dominant use of the paretic leg to support the
      body may be useful as a rehabilitative treatment to improve the kinetic abilities
      in the paretic stance period.

PMID- 22133243
TI  - Musculoskeletal pain and overuse syndromes in adult acquired major upper-limb
      amputees.
AB  - OBJECTIVES: (1) To compare the prevalence of self-reported musculoskeletal pain
      in upper-limb amputees (ULAs) in Norway with that of a control group drawn from
      the Norwegian general population; (2) to describe musculoskeletal pain
      bothersomeness in ULAs; (3) to estimate the association between prosthesis wear
      and self-reported musculoskeletal pain in ULAs; and (4) to describe the
      occurrence of musculoskeletal overuse syndromes in a sample of ULAs. DESIGN:
      Cross-sectional study: postal questionnaires and clinical examinations. SETTING:
      Norwegian ULA population. Clinical examinations performed at 3 clinics.
      PARTICIPANTS: Questionnaires: population-based amputee sample (n=224; 57.4%
      response rate). Random control sample (n=318; 33.1% response rate). Clinical
      examinations: combined referred sample and convenience sample (n=70; 83.3% of
      those invited). Survey inclusion criteria: adult, resident in Norway and
      mastering Norwegian (amputees and controls), acquired major upper-limb amputation
      (amputees only). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Self
      reported musculoskeletal pain and pain bothersomeness. Self-reported pain in
      prosthesis wearers and nonwearers. Clinically assessed diagnoses of
      musculoskeletal overuse syndromes. RESULTS: Self-reported musculoskeletal pain
      was more frequent in ULAs than in the control group except for lower back pain.
      In ULAs, 57.0% reported neck/upper back pain (odds ratio [OR]=2.56; 95%
      confidence interval [CI], 1.64-3.98), and 58.9% reported shoulder pain (OR=4.00;
      95% CI, 2.51-6.36). The percentage difference for arm pain was 24.8% (P<.001).
      All pain was reported as bothersome. We found no difference in pain prevalence
      between prosthesis wearers and nonwearers. Musculoskeletal overuse syndromes were
      found in 6.1% to 24.2% of ULAs, depending on diagnosis and case-definition
      criteria. CONCLUSIONS: Upper-limb loss increases the risk of self-reported
      musculoskeletal pain in the neck/upper back, shoulders, and in the remaining arm.
      Prosthesis wear does not prevent musculoskeletal pain. Further studies should be
      conducted to investigate the effects of prosthesis wear and possible preventive
      measures, and to ascertain our preliminary prevalence estimates of overuse
      syndromes.

PMID- 22133244
TI  - Point of entry and functional outcomes after comprehensive day treatment
      participation.
AB  - OBJECTIVES: To explore the relationship between point of entry into a
      comprehensive day treatment (CDT) program and outcomes after acquired brain
      injury (ABI). We hypothesized that participants entering our program 0 to 6
      months postinjury would demonstrate greater declines in neurobehavioral sequelae
      and improvements in residential/vocational independence than those entering >6 to
      12 and >12 to 24 months postinjury. DESIGN: Retrospective examination of
      admission, discharge, and 1-year follow-up data from a CDT program. SETTING: A
      large Midwestern academic medical center. PARTICIPANTS: Adult CDT participants
      with traumatic brain injuries (TBI) (n=54) or cerebrovascular accidents (CVAs)
      (n=29). INTERVENTIONS: A CDT rehabilitation program. MAIN OUTCOME MEASURES:
      Portland Adaptability Inventory/Mayo-Portland Adaptability Inventory (percent
      change scores between admission and discharge) and the Independent Living and
      Vocational Independence Scales. RESULTS: Time since injury was categorically
      coded into the 3 aforementioned point of entry groups. A 2 (injury type) * 3
      (point of entry) between subjects analysis of covariance revealed a significant
      main effect for the point of entry (P<.001). Post hoc tests indicated that
      individuals entering the program 0 to 6 months postinjury demonstrated
      significantly greater treatment gains than those entering 6 to 12 or 12 to 24
      months postinjury. Within group chi-square analyses revealed that a significantly
      higher percentage of the early entry participants were living and working
      independently at discharge and 1-year follow-up. CONCLUSIONS: Entry into a CDT
      program (0-6mo postinjury) is associated with significantly greater declines in
      neurobehavioral sequelae and improvements in residential and vocational
      independence in participants with TBI or CVA. Sustainable modest treatment gains
      were also observed in the late entry groups, suggesting that these individuals
      also benefit significantly from CDT program participation.

PMID- 22133246
TI  - Contribution of ischemic stroke to hip fracture risk and the influence of gender
      difference.
AB  - OBJECTIVES: To clarify the contribution of stroke to the risk of hip fracture
      (HF) and the influence of gender difference on HF, and to estimate the incidence
      rate of poststroke HF. DESIGN: A prospective, probability-sampling, 10-year,
      population-based cohort study. SETTING: A National Health Insurance Research
      Database consisting of 200,432 randomly selected enrollees. PARTICIPANTS:
      Subjects with acute ischemic stroke (N=1951; mean age +/- SD, 65.6 +/- 9.8y;
      56.5% men) were identified. For each stroke subject, 2 age- and gender-matched
      controls were recruited. Control subjects did not have any brain disease. Those
      subjects younger than 45 years were excluded. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The incidence rate and the adjusted hazard ratio of sustaining
      an HF were estimated. The cumulative HF-free probability was plotted. RESULTS:
      Stroke subjects had a higher incidence rate of HF than their controls (women:
      11.3 vs 4.4/1000 person-years, P<.001; men: 5.6 vs 2.9/1000 person-years,
      P<.001). The risk of HF was higher among stroke subjects, yielding an adjusted
      hazard ratio (95% confidence interval) of 2.33 (1.62-3.34) for women and 1.73
      (1.12-2.68) for men. Compared with men with stroke, women with stroke had an
      adjusted hazard ratio of 1.83 (1.18-2.85). Stroke subjects had a lower cumulative
      HF-free probability throughout the 10-year duration than did the control subjects
      (women, P<.001; men, P=.005). Half of the poststroke HFs occurred within 2.5
      years of the onset of stroke. CONCLUSIONS: Ischemic stroke is a risk factor for
      HF, which is at work over and beyond age and gender. Being a woman with stroke
      increases this fracture risk. An active program for fracture prevention might
      prove effective for stroke subjects, and this may be especially true for women.

PMID- 22133245
TI  - Associations between perceived proximity to neighborhood resources, disability,
      and social participation among community-dwelling older adults: results from the
      VoisiNuAge study.
AB  - OBJECTIVE: To examine the associations between perceived proximity to
      neighborhood resources, disability, and social participation and the potential
      moderating effect of perceived proximity to neighborhood resources on the
      association between disability and social participation in community-dwelling
      older women and men. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS:
      Older adults (296 women, 258 men). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Data for age, education, depressive symptoms, frequency of
      participation in community activities, perceived proximity to neighborhood
      resources (services, amenities), and functional autonomy in daily activities
      (disability) were collected by means of interviewer-administered questionnaire.
      RESULTS: Greater perceived proximity to resources and lower level of disability
      were associated with greater social participation for both women (R(2)=.10;
      P<.001) and men (R(2)=.05; P<.01). The association between disability and social
      participation did not vary as a function of perceived proximity to neighborhood
      resources in women (no moderating effect; P=.15). However, in men, greater
      perceived proximity to neighborhood resources enhanced social participation
      (P=.01), but only in those with minor or no disability. CONCLUSIONS: Future
      studies should investigate why perceived proximity to services and amenities is
      associated with social participation in older men with minor or no disabilities
      and with women overall, but has no association in men with moderate disabilities.

PMID- 22133247
TI  - The association between decline in physical functioning and atrophy of medial
      temporal areas in community-dwelling older adults with amnestic and nonamnestic
      mild cognitive impairment.
AB  - OBJECTIVE: To examine whether declining performance in aspects of physical
      functioning, including lower extremity muscle strength, 1-legged balance, walking
      speed, and exercise capacity, is associated with atrophy of medial temporal areas
      in community-dwelling older adults with mild cognitive impairment (MCI). DESIGN:
      Cross-sectional study. SETTING: General community in Japan. PARTICIPANTS:
      Community-dwelling older adults 65 years and older with a Clinical Dementia
      Rating of 0.5 or memory complaints were enrolled in this study. This study
      examined 34 participants with amnestic MCI (aMCI) and 58 nonamnestic MCI (non
      aMCI) participants. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The
      following physical performance tests were conducted: muscle strength of knee
      extension, 1-legged standing time, 5-m walking test, and 6-minute walk test
      (6MWT). The z scores of the voxel-based specific regional analysis system for
      Alzheimer's disease were determined to assess the degree of atrophy in the
      bilateral medial temporal areas including the entorhinal cortex (MTA-ERC).
      RESULTS: In the aMCI group, 6MWT performance was associated with MTA-ERC atrophy
      (beta=-.462, P=.014) after controlling for age. In the stepwise multiple
      regression analyses, 6MWT and body mass index were found to be significant
      determinants of MTA-ERC atrophy in all participants (R(2)=.275), as well as the
      aMCI and non-aMCI groups when analyzed separately (R(2)=.418 and R(2)=.216,
      respectively). CONCLUSIONS: A decline in exercise capacity was found to be more
      closely associated with atrophy of the MTA-ERC compared with other aspects of
      physical functioning in older adults with MCI, especially the amnestic type.
      These findings suggest that it is important for future studies to investigate the
      effects of increased aerobic activity and improved fitness on brain volume in
      older adults at risk of developing dementia.

PMID- 22133248
TI  - Cardiorespiratory response to exercise testing in individuals with Alzheimer's
      disease.
AB  - OBJECTIVE: To examine exercise testing response in Alzheimer's disease (AD) and
      possible disease-related change over time. DESIGN: Retrospective assessment of a
      2-year observational study. SETTING: University medical center. PARTICIPANTS:
      Individuals without dementia (n=50) and with AD (n=31). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Participants underwent a clinical dementia
      evaluation and performed an incremental exercise test using a treadmill and the
      modified Bruce protocol at baseline and at a 2-year follow-up. We examined oxygen
      consumption, minute ventilation, heart rate, and ventilatory equivalents for
      oxygen and carbon dioxide at submaximal and peak exercise intensities to
      determine whether the measures were different between groups or over time.
      RESULTS: Participants with AD and those without dementia performed similarly at
      submaximal effort, and both groups showed similar changes in exercise response
      over 2 years. However, nondemented individuals had consistently higher values of
      oxygen consumption (P<=.02) and minute ventilation at peak effort at baseline
      (P=.003). CONCLUSIONS: Individuals with AD demonstrate physiologic responses to
      submaximal exercise effort that are not significantly different than individuals
      without dementia. However, differences are apparent at the extreme of effort.

PMID- 22133249
TI  - Stair negotiation time in community-dwelling older adults: normative values and
      association with functional decline.
AB  - OBJECTIVES: To establish reference values for stair ascent and descent times in
      community-dwelling, ambulatory older adults, and to examine their predictive
      validity for functional decline. DESIGN: Longitudinal cohort study. Mean follow
      up time was 1.8 years (maximum, 3.2y; total, 857.9 person-years). SETTING:
      Community sample. PARTICIPANTS: Adults 70 years and older (N=513; mean age, 80.8
      +/- 5.1y) without disability or dementia. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Time to ascend and descend 3 steps measured at baseline. A 14
      point disability scale assessed functional status at baseline and at follow-up
      interviews every 2 to 3 months. Functional decline was defined as an increase in
      the disability score by 1 point during the follow-up period. RESULTS: The mean+/
      SD stair ascent and descent times for 3 steps were 2.78 +/- 1.49 and 2.83 +/-
      1.61 seconds, respectively. The proportion of self-reported and objective
      difficulty was higher with longer stair ascent and descent times (P<.001 for
      trend for both stair ascent and descent). Of the 472 participants with at least 1
      follow-up interview, 315 developed functional decline, with a 12-month cumulative
      incidence of 56.6% (95% confidence interval [CI], 52.1%-61.3%). The stair
      negotiation time was a significant predictor of functional decline after
      adjusting for covariates including gait velocity (adjusted hazard ratio [aHR] per
      1-s increase: aHR=1.12 [95% CI, 1.04-1.21] for stair ascent time; aHR=1.15 [95%
      CI, 1.07-1.24] for stair descent time). Stair descent time was a significant
      predictor of functional decline among relatively high functioning older adults
      reporting no difficulty in stair negotiation (P=.001). CONCLUSIONS: The stair
      ascent and descent times are simple, quick, and valid clinical measures for
      assessing the risk of functional decline in community-dwelling older adults
      including high-functioning individuals.

PMID- 22133250
TI  - Assessing Physical Activity in Inpatient Rehabilitation: validity, practicality,
      and sensitivity to change in the physical activity in inpatient rehabilitation
      assessment.
AB  - OBJECTIVE: To validate a novel assessment of inpatient physical activity. DESIGN:
      Prospective cohort study for the evaluation of a novel questionnaire for physical
      activity in geriatric inpatients. SETTING: German geriatric inpatient
      rehabilitation unit. PARTICIPANTS: Patients (N=96; 67 [72%] women; median age,
      81y) with a variety of main underlying diagnoses, including musculoskeletal
      diseases, hip fracture, cardiovascular diseases, stroke, and others.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Ceiling and floor effects
      and administration time were measured. For criterion-related concurrent validity
      (convergent and discriminative), the Physical Activity in Inpatient
      Rehabilitation Assessment (PAIR) was administered in parallel to self-rated,
      proxy-rated, and performance-based measures of physical function at admission.
      Measurements were repeated at discharge and 4-month follow-up in the home
      environment, including a standard physical activity questionnaire to determine
      predictive validity. Spearman correlation coefficients were calculated to
      describe associations between parameters. Sensitivity to change was estimated
      using standardized response means (SRMs). RESULTS: Administration time of the
      PAIR ranged from less than 1 to 4 minutes. Ceiling effects occurred mainly at
      discharge (5%-14%), and floor effects (5%-11%), at admission. There were no
      missing values. Associations between convergent and predictive validity measures
      and functional measures (r=.43-.53, r=.49-.54, respectively) were clearly better
      when cognition was intact. Discriminative validity expressed as effect sizes
      ranged from .27 to 1.44. The SRM to describe sensitivity to change was .65 for
      the total score. CONCLUSIONS: The PAIR is the first validated questionnaire to
      assess physical activity in geriatric inpatients. It is practical and its
      validity and sensitivity to change are similar to existing physical activity
      questionnaires for community-dwelling older persons.

PMID- 22133251
TI  - Constant work-rate test to assess the effects of intradialytic aerobic training
      in mildly impaired patients with end-stage renal disease: a randomized controlled
      trial.
AB  - OBJECTIVE: To investigate if high-intensity constant work rate (CWR) would
      constitute a more appropriate testing strategy compared with incremental work
      rate (IWR) to assess the effectiveness of intradialytic aerobic training in
      patients with end-stage renal disease (ESRD). DESIGN: Randomized controlled
      trial. SETTING: Nephrology unit at the university hospital. PARTICIPANTS:
      Patients (N=28; 47.0+/-11.9y) under hemodialysis (4.4+/-4.3y) were randomly
      assigned to exercise and control groups. INTERVENTION: Patients included in the
      exercise group underwent a moderate-intensity intradialytic aerobic training
      program 3 times per week for 12 weeks. MAIN OUTCOME MEASURES: Cardiopulmonary and
      perceptual responses were obtained during an IWR and a high-intensity CWR test to
      the limit of tolerance on a cycle ergometer. RESULTS: Training-induced increases
      in peak oxygen uptake (Vo(2)peak) and time to exercise intolerance (Tlim). Mean
      improvement in Tlim (97.4%+/-75.6%) was significantly higher than increases in
      Vo(2)peak (12%+/-11.3%) (P<.01); in fact, while Tlim improved 50% to 200% in 9 of
      12 patients, Vo(2)peak increases were typically in the 15% to 20% range. CWR test
      revealed lower metabolic, ventilatory, cardiovascular, and subjective stresses at
      isotime; in contrast, submaximal responses during the incremental work rate (at
      the gas exchange threshold) remained unaltered after training. CONCLUSIONS: A
      laboratory-based measure of endurance exercise capacity (high-intensity CWR test
      to Tlim) was substantially more sensitive than oxygen uptake at the peak IWR test
      to unravel the physiologic benefits of an intradialytic aerobic training program
      in mildly impaired patients with ESRD.

PMID- 22133252
TI  - Is insomnia associated with suicidality in stroke?
AB  - OBJECTIVE: To evaluate the relationship between insomnia and suicidality (SI) in
      Chinese patients with first or recurrent stroke. DESIGN: Cross-sectional survey.
      SETTING: Acute stroke unit of a general hospital. PARTICIPANTS: Patients (N=787)
      with acute ischemic stroke admitted to the acute stroke unit of a university
      affiliated regional hospital in Hong Kong. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Suicidality (SI) was assessed with the Geriatric Mental State
      Examination at 3 months after subjects' index stroke. Insomnia symptoms were
      evaluated with a standard insomnia questionnaire. The association between
      insomnia symptoms and SI was examined and adjusted for potential confounders,
      including age, sex, marital status, previous stroke, depression, fatigue, Mini
      Mental State Examination score, and neurologic deficits measured with the
      National Institutes of Health Stroke Scale. RESULTS: Eighty-seven patients
      (11.1%) were found to have SI (SI group). Frequent awakening was significantly
      more common in the SI group than in the non-SI group and remained a significant
      predictor of SI in forward logistic regression analysis (odds ratio, 1.7) after
      adjusting for possible confounders. CONCLUSIONS: These findings should alert
      clinicians to the potential danger of insomnia and the importance of its early
      identification and treatment in stroke patients.

PMID- 22133253
TI  - Walking and thinking in persons with multiple sclerosis who vary in disability.
AB  - OBJECTIVE: To examine the effect of a cognitive task on spatiotemporal parameters
      of gait in persons with multiple sclerosis (MS) with varying disability. DESIGN:
      Cohort. SETTING: Testing occurred at a local hospital. PARTICIPANTS: Community
      living persons (N=78) with MS participated in this investigation. They were
      divided into 3 groups based on Expanded Disability Status Scale (EDSS) scores:
      mild (2.0-3.5 EDSS; n=21); moderate (4.0-5.5 EDSS; n=25); and severe (6.0-6.5
      EDSS; n=32). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants
      walked at a self-selected pace on an electronic pathway, which recorded
      spatiotemporal parameters of gait, in 4 separate trials and completed a cognitive
      task in the last 2 trials. The effect of the cognitive task was quantified as the
      change in spatiotemporal parameters of gait. RESULTS: There was an overall
      decline in gait with the additive cognitive task. The magnitude of the adverse
      changes ranged from 1.8% for step length (P=.02) to 12% for gait velocity
      (P<.001). Moreover, adverse changes in gait function were greatest in the severe
      and moderate disability group (P<.05). CONCLUSIONS: Persons with MS have impaired
      walking while doing a cognitive task, and the adverse effect of a cognitive task
      on walking function is greatest in persons with severe and moderate disability.
      Difficulty walking while thinking has implications for everyday life and may be
      related to the risk of falls. Further work is needed to determine whether the
      adverse effect of an additive cognitive task can be minimized with rehabilitative
      interventions.

PMID- 22133254
TI  - Comparison of 3 different methods to analyze ankle plantarflexor stiffness in
      children with spastic diplegia cerebral palsy.
AB  - OBJECTIVE: To compare 3 different methods of measuring plantarflexor stiffness in
      children with spastic diplegia cerebral palsy (CP) and children without
      disability. DESIGN: Case-control study. SETTING: Human performance laboratory.
      PARTICIPANTS: A retrospective analysis was conducted with children with spastic
      diplegia (n=121; mean age, 8.4y) and children with typical development (TD)
      (n=48; mean age, 9.7y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: An
      isokinetic dynamometer was used to measure ankle plantarflexor stiffness at 10
      degrees /s using 3 methods: (1) end-range method, which applied a linear slope to
      the end of the torque-angle curve; (2) set-range method, which applied a linear
      slope from 30 degrees  to 10 degrees  plantarflexion; and (3) a linear method,
      which applied a slope only to the linear portion of the curve. RESULTS: Two-way
      analysis of variance revealed significant main effects for group and stiffness
      method. The end-range method showed no significant difference between groups for
      plantarflexor stiffness (P=.62), the set-range method showed the CP group with
      120% greater stiffness than the TD group (P<.046), and the linear method showed
      the CP group with 35% greater stiffness than the TD group (P<.001). CONCLUSIONS:
      The linear method appeared to resolve the issues with the previous methods;
      applying a linear slope to a nonlinear curve or applying a linear slope to the
      same range of motion for each child regardless of their range limitations. It is
      clear that children with CP have limited range of motion; therefore, stiffness
      occurs earlier in the range than would be expected for a typically developing
      child. Using the linear method, children with CP were 35% stiffer in the ankle
      plantarflexors than typically developing peers.

PMID- 22133255
TI  - The effect of neuroscience education on pain, disability, anxiety, and stress in
      chronic musculoskeletal pain.
AB  - OBJECTIVE: To evaluate the evidence for the effectiveness of neuroscience
      education (NE) for pain, disability, anxiety, and stress in chronic
      musculoskeletal (MSK) pain. DATA SOURCES: Systematic searches were conducted on
      Biomed Central, BMJ.com, CINAHL, the Cochrane Library, NLM Central Gateway, OVID,
      ProQuest (Digital Dissertations), PsycInfo, PubMed/Medline, ScienceDirect, and
      Web of Science. Secondary searching (PEARLing) was undertaken, whereby reference
      lists of the selected articles were reviewed for additional references not
      identified in the primary search. STUDY SELECTION: All experimental studies
      including randomized controlled trials (RCTs), nonrandomized clinical trials, and
      case series evaluating the effect of NE on pain, disability, anxiety, and stress
      for chronic MSK pain were considered for inclusion. Additional limitations:
      studies published in English, published within the last 10 years, and patients
      older than 18 years. No limitations were set on specific outcome measures of
      pain, disability, anxiety, and stress. DATA EXTRACTION: Data were extracted using
      the participants, interventions, comparison, and outcomes (PICO) approach. DATA
      SYNTHESIS: Methodological quality was assessed by 2 reviewers using the Critical
      Review Form-Quantitative Studies. This review includes 8 studies comprising 6
      high-quality RCTs, 1 pseudo-RCT, and 1 comparative study involving 401 subjects.
      Most articles were of good quality, with no studies rated as poor or fair.
      Heterogeneity across the studies with respect to participants, interventions
      evaluated, and outcome measures used prevented meta-analyses. Narrative synthesis
      of results, based on effect size, established compelling evidence that NE may be
      effective in reducing pain ratings, increasing function, addressing
      catastrophization, and improving movement in chronic MSK pain. CONCLUSIONS: For
      chronic MSK pain disorders, there is compelling evidence that an educational
      strategy addressing neurophysiology and neurobiology of pain can have a positive
      effect on pain, disability, catastrophization, and physical performance.

PMID- 22133256
TI  - Selection for inpatient rehabilitation after acute stroke: a systematic review of
      the literature.
AB  - OBJECTIVE: To identify patient-related factors that have been found to correlate
      with functional outcomes post acute stroke to guide clinical decision making with
      regard to rehabilitation admission after acute stroke. DATA SOURCES: We
      systematically searched the scientific literature between 1966 and January 2010.
      The primary source of studies was the electronic databases Medline, CINAHL, and
      Embase. The search was supplemented with citation tracking. STUDY SELECTION: Two
      reviewers independently applied the inclusion criteria to identify relevant
      articles from the citations obtained through the literature search. Eligible
      studies included systematic reviews of prognostic indicators, studies of
      prognostic indicators of acute discharge disposition, and studies of
      rehabilitation admission criteria after acute stroke. Of the 8895 studies
      identified, 83 articles, representing 79 studies, were included in the review.
      DATA EXTRACTION: One reviewer extracted the data relating to the participants,
      prognostic indicators, and outcomes. A second reviewer independently checked data
      extracted with disagreement resolved by a third reviewer. Quality of included
      studies was assessed for internal and external validity. DATA SYNTHESIS: Of the
      79 studies, 26 were systematic reviews of prognostic indicators of functional
      level and/or discharge disposition, 48 were studies of prognostic indicators of
      acute discharge disposition, and 6 were studies of rehabilitation selection
      criteria. The methodologic quality of the included studies was generally poor.
      Age, cognition, functional level after stroke, and, to a lesser extent,
      continence were found to have a consistent association with outcome across all 3
      research areas. In addition, stroke severity was also associated with acute
      discharge disposition, final discharge disposition, and functional level. Sex and
      side of stroke appeared to have no association across all 3 of the research
      areas. CONCLUSIONS: This review highlights a number of important prognostic
      indicators and rehabilitation selection criteria that may assist clinicians in
      improving selection procedures and standardizing access to inpatient
      rehabilitation after stroke, although the quality of many studies is low. Further
      high quality studies and reviews of prognostic indicators and clinician decision
      making with regards to rehabilitation acceptance are required.

PMID- 22133257
TI  - Clinimetric evaluation of questionnaires used to assess activity after traumatic
      brachial plexus injury in adults: a systematic review.
AB  - OBJECTIVES: To identify upper limb questionnaires used in the brachial plexus
      injury (BPI) literature to assess activities and to evaluate their clinimetric
      properties. DATA SOURCES; STUDY SELECTION; DATA EXTRACTION: This systematic
      review was undertaken in 2 stages. In stage 1, 10 electronic databases and 1
      Internet journal were searched for quantitative studies (ie, randomized
      controlled trials, comparative studies, case series, and case studies) that
      evaluated outcome after BPI, irrespective of language or date of publication,
      from date of database inception to September 2010. All outcome instruments used
      were extracted and classified using the International Classification of
      Functioning, Disability and Health framework. Questionnaires were identified that
      apportioned >50% of the total score to the assessment of upper limb activity. In
      stage 2, 4 electronic databases were searched for papers that evaluated the
      clinimetric properties of all identified activity questionnaires with respect to
      peripheral nerve injuries of the upper limb. Two independent reviewers assessed
      the clinimetric properties of identified questionnaires according to standardized
      criteria. DATA SYNTHESIS: Stage 1 identified 4324 papers, of which 265 met the
      inclusion criteria. One hundred and three outcome measures were identified, the
      majority of which assess body function or body structure. Twenty-nine
      questionnaires assessed upper limb activity. Two questionnaires, the ABILHAND and
      Disability of the Arm, Shoulder and Hand (DASH), attributed >50% of the overall
      score to activity of the upper limb. The DASH had some published evidence of
      clinimetric properties in individuals with peripheral nerve injuries. Neither had
      been clinimetrically evaluated for BPI, nor met all quality criteria.
      CONCLUSIONS: Day-to-day activities of the upper limb are infrequently evaluated
      after BPI. While attempts have been made to measure activity, there is a paucity
      of clinimetric evidence on activity questionnaires for individuals with BPI. We
      recommend that a core set of items be developed which evaluate activity, as well
      a body structure, body function, and participation.

PMID- 22133258
TI  - Fear of falling does not alter the kinematics of recovery from an induced trip: a
      preliminary study.
AB  - OBJECTIVE: To provide preliminary information about the relationships between
      self-reported fear of falling (FOF) in healthy community-dwelling women, number
      of falls, and recovery kinematics in response to a laboratory-induced trip.
      DESIGN: Cohort study. SETTING: Clinical research laboratory. PARTICIPANTS: A
      subset of community-dwelling older women (N=33) recruited from studies of
      laboratory-induced trips and fall prevention. INTERVENTION: A laboratory-induced
      trip. MAIN OUTCOME MEASURES: Number of fallers in the FOF group versus the
      control group. Recovery kinematics of FOF group falls versus control group falls,
      and FOF group recoveries versus control group recoveries were compared. Degree of
      FOF was assessed by using the Activities-Specific Balance Confidence (ABC) Scale.
      RESULTS: Falls occurred in 6 of 14 (43%) FOF and 4 of 16 (25%) control subjects
      (P=.26). The kinematics of FOF group falls were similar to those of control group
      falls. At completion of the initial recovery step, the FOF group showed
      significantly greater trunk extension velocity than controls (-82.1 degrees /s +/
      -66.1 degrees /s vs -25.0 degrees /s +/- -53.0 degrees /s, respectively; P=.05).
      All other variables were not significantly different. ABC Scale scores of FOF
      subjects did not differ significantly between fallers and those who recovered
      (mean, 75.2 +/- 5.6, 71.1 +/- 11.8, respectively; P=.84). CONCLUSION: Healthy
      community-dwelling older adults would benefit from fall prevention regardless of
      the presence of self-reported FOF.

PMID- 22133259
TI  - Applying a new participation definition with pediatric populations: issues and
      challenges.

PMID- 22133262
TI  - Tuberculosis verrucosa cutis with elevation of circulating T-helper 1 and 17
      cells and their reductions after successful treatment.

PMID- 22133261
TI  - SND2, a NAC transcription factor gene, regulates genes involved in secondary cell
      wall development in Arabidopsis fibres and increases fibre cell area in
      Eucalyptus.
AB  - BACKGROUND: NAC domain transcription factors initiate secondary cell wall
      biosynthesis in Arabidopsis fibres and vessels by activating numerous
      transcriptional regulators and biosynthetic genes. NAC family member SND2 is an
      indirect target of a principal regulator of fibre secondary cell wall formation,
      SND1. A previous study showed that overexpression of SND2 produced a fibre cell
      specific increase in secondary cell wall thickness in Arabidopsis stems, and that
      the protein was able to transactivate the cellulose synthase8 (CesA8) promoter.
      However, the full repertoire of genes regulated by SND2 is unknown, and the
      effect of its overexpression on cell wall chemistry remains unexplored. RESULTS:
      We overexpressed SND2 in Arabidopsis and analyzed homozygous lines with regards
      to stem chemistry, biomass and fibre secondary cell wall thickness. A line
      showing upregulation of CesA8 was selected for transcriptome-wide gene expression
      profiling. We found evidence for upregulation of biosynthetic genes associated
      with cellulose, xylan, mannan and lignin polymerization in this line, in
      agreement with significant co-expression of these genes with native SND2
      transcripts according to public microarray repositories. Only minor alterations
      in cell wall chemistry were detected. Transcription factor MYB103, in addition to
      SND1, was upregulated in SND2-overexpressing plants, and we detected upregulation
      of genes encoding components of a signal transduction machinery recently proposed
      to initiate secondary cell wall formation. Several homozygous T4 and hemizygous
      T1 transgenic lines with pronounced SND2 overexpression levels revealed a
      negative impact on fibre wall deposition, which may be indirectly attributable to
      excessive overexpression rather than co-suppression. Conversely, overexpression
      of SND2 in Eucalyptus stems led to increased fibre cross-sectional cell area.
      CONCLUSIONS: This study supports a function for SND2 in the regulation of
      cellulose and hemicellulose biosynthetic genes in addition of those involved in
      lignin polymerization and signalling. SND2 seems to occupy a subordinate but
      central tier in the secondary cell wall transcriptional network. Our results
      reveal phenotypic differences in the effect of SND2 overexpression between woody
      and herbaceous stems and emphasize the importance of expression thresholds in
      transcription factor studies.

PMID- 22133264
TI  - Improving patient experience with spinal cord stimulation: implications of
      position-related changes in neurostimulation.
AB  - OBJECTIVES:   The objective of this narrative review is to discuss the clinical
      implications of position-related changes in spinal cord stimulation and
      technological improvements to better meet patient needs. METHODS:   Keywords
      applicable to spinal cord stimulation therapy, including paresthesia perception,
      spinal cord position, lead impedance, and sensor technologies, were searched in
      the PubMed, EMBASE, and Cochrane Library databases. Literature analysis, combined
      with extensive clinical experience with spinal cord stimulation therapy, forms
      the basis of this review. RESULTS:   Fluctuations in paresthesia perception are
      largely caused by variation in the distance between the fixed electrodes and the
      spinal cord consequent to patient movement. Patients employ multiple strategies
      with varying success to manage position-related fluctuations in stimulation
      perception, which may result in suboptimum therapy delivery. CONCLUSIONS:   A new
      type of spinal cord stimulation system that incorporates accelerometer technology
      to automatically adjust stimulation amplitude based on patient position may
      better meet patient analgesic needs and is in early clinical application.

PMID- 22133263
TI  - Noninvasive testing of lung function and inflammation in pediatric patients with
      acute asthma exacerbations.
AB  - OBJECTIVE: There is limited information on performance rates for tests of lung
      function and inflammation in pediatric patients with acute asthma exacerbations.
      We sought to examine how frequently pediatric patients with acute asthma
      exacerbations could perform noninvasive lung function and exhaled nitric oxide
      (FE(NO)) testing and participant characteristics associated with successful
      performance. METHODS: We studied a prospective convenience sample aged 5-17 years
      with acute asthma exacerbations in a pediatric emergency department. Participants
      attempted spirometry for percent predicted forced expiratory volume in 1 second
      (%FEV(1)), airway resistance (Rint), and FE(NO) testing before treatment. We
      examined overall performance rates and the associations of age, gender, race, and
      baseline acute asthma severity score with successful test performance. RESULTS:
      Among 573 participants, age was (median [interquartile range]) 8.8 [6.8, 11.5]
      years, 60% were male, 57% were African-American, and 58% had Medicaid insurance.
      Tests were performed successfully by the following [n (%)]: full American
      Thoracic Society-European Respiratory Society criteria spirometry, 331 (58%);
      Rint, 561 (98%); and FE(NO), 354 (70% of 505 attempted test). Sixty percent with
      mild-moderate exacerbations performed spirometry compared to 17% with severe
      exacerbations (p = .0001). Participants aged 8-12 years (67%) were more likely to
      perform spirometry than those aged 5-7 years (48%) (OR = 2.23, 95% CI: 1.45-3.11)
      or 13-17 years (58%) (OR = 1.61, 95% CI: 1.00-2.59). CONCLUSIONS: There is
      clinically important variability in performance of these tests during acute
      asthma exacerbations. The proportion of patients with severe exacerbations able
      to perform spirometry (17%) limits its utility. Almost all children with acute
      asthma can perform Rint testing, and further development and validation of this
      technology is warranted.

PMID- 22133265
TI  - Cyclic ether-containing macrolactins, antimicrobial 24-membered isomeric
      macrolactones from a marine Bacillus sp.
AB  - Bioassay-guided isolation of bioactive metabolites from the ethyl acetate extract
      of a marine Bacillus sp. fermentation broth has led to the discovery of three new
      24-membered macrolactones, macrolactins 1-3, which contain an oxetane, an
      epoxide, and a tetrahydropyran ring, respectively. The configurations of 1-3 were
      assigned by a combination of coupling constants, ROESY data analysis, and
      application of the modified Mosher's method. Compounds 1-3 showed in vitro
      antimicrobial activity.

PMID- 22133266
TI  - Monocytes from tuberculosis patients that exhibit cleaved caspase 9 and
      denaturalized cytochrome c are more susceptible to death mediated by Toll-like
      receptor 2.
AB  - Experimental models have shown that lipoproteins from Mycobacterium tuberculosis
      induce apoptosis via Toll-like receptor 2 (TLR2) in the THP-1 cell line and in
      monocyte-derived macrophages from healthy volunteers. We found an increased
      percentage of circulating monocytes in patients with tuberculosis (TB) in
      comparison to healthy controls. Patients with TB showed a higher TLR2 and TLR4
      expression density on monocytes, and a higher proportion of TLR2(+)  monocytes,
      as well as increased serum tumour necrosis factor-alpha level. In culture,
      monocytes from TB patients were more susceptible to death than monocytes from
      healthy controls. Moreover, death-susceptible monocytes were positive to both
      TLR2 and TLR4 at the start of culture. Freshly obtained monocytes from TB
      patients exhibited cleaved caspase 9 and denaturalized cytochrome c. For levels
      of caspase 8, apoptosis-regulating signal kinase 1, and phospho-p38 mitogen
      activated protein kinase there was no difference between samples from TB patients
      and from healthy controls. The culture filtrate antigen extract from M.
      tuberculosis H37Rv strain induced the death of monocytes from patient with TB
      after a 4-hr incubation, which was abrogated by neutralizing antibodies for TLR2
      but not TLR4. Similarly, Pam3CSK4, a synthetic agonist triacylated ligand to
      TLR2, also induced the death of monocytes, although it did not increase levels of
      cleaved caspase 9. Our findings suggest that monocytes from TB patients are more
      susceptible to death, probably through mitochondrial damage, and that cell death
      increases in the presence of mycobacterial antigen by a TLR2-dependent pathway.

PMID- 22133267
TI  - Antidiabetic activity of isoquercetin in diabetic KK -Ay mice.
AB  - BACKGROUND: Tartary buckwheat bran is an important natural source of quercetin
      and isoquercetin. Quercetin and isoquercetin are both powerful alpha-glucosidase
      inhibitors. Although the IC50 of isoquercetin as alpha-glucosidase inhibitor was
      much higher than that of quercetin, the bioavailability of isoquercetin was
      higher than that of quercetin. Hence, we are interested in the antidiabetic
      effect of isoquercetin in diabetic KK -Ay mice. METHODS: The hypoglycemic effect
      of isoquercetin in a type 2 diabetic animal model (KK-Ay mice) was studied.
      Isoquercetin was administrated at doses of 50, 100 and 200 mg/kg for 35 days.
      RESULTS: It was found that fasting blood glucose concentration was decreased with
      the 200 mg/kg group (p < 0.01) the most efficient compared with the diabetic
      control group. In addition, there was significant decrease in plasma C-peptide,
      triglyceride, total cholesterol and blood urea nitrogen levels after 35 days.
      Meanwhile, glucose tolerance was improved, and the immunoreactive of pancreatic
      islets beta-cells was promoted. CONCLUSIONS: These results suggest that
      isoquercetin had a regulative role in blood glucose level and lipids, and
      improved the function of pancreatic islets. Isoquercetin may be useful in the
      treatment of type 2 diabetes mellitus.

PMID- 22133268
TI  - Increased stress-induced dopamine release in psychosis.
AB  - BACKGROUND: A pathologic response to common life stressors, in which a
      hyperresponsive dopaminergic system is thought to play a key role, is a potential
      etiologic factor in the triggering and relapse of psychosis. However, there is no
      direct evidence that brain dopaminergic response to stress is exaggerated in
      psychosis. METHODS: Using the ability of endogenous dopamine (DA) to compete with
      [(11)C]-(+)-PHNO binding, as measured with positron emission tomography, we
      examined stress-induced DA release in response to a validated psychosocial stress
      task. We studied 12 clinical high-risk (CHR), 10 antipsychotic-naive subjects
      with schizophrenia (SCZ), and 12 matched healthy volunteers (HV). Stress-induced
      DA release was estimated as the percent change in binding potential between
      conditions (stress and control scan) in the striatal subdivisions: limbic
      striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST).
      RESULTS: We found a significant difference between groups in the AST (F = 8.13,
      df = 2,31, p = .001), and at the SMST (F = 3,64, df = 2,31, p = .03) but not in
      the LST (F = .43, df = 2,31, p = .40) with CHR and SCZ having larger [(11)C]-(+)
      PHNO displacement in response to the stress. Bonferroni-corrected comparisons
      confirmed that HV displacement (-2.86%) in the AST was significantly different in
      CHR (6.97%) and SCZ (11.44%) (with no significant difference between CHR and
      SCZ). CONCLUSIONS: This study reveals a sensitized dopaminergic response to
      stress in a psychiatric condition and may have important theoretical and clinical
      implications regarding efforts to abort or delay relapse and/or conversion to
      psychosis.

PMID- 22133269
TI  - Animal models for investigating chronic pancreatitis.
AB  - Chronic pancreatitis is defined as a continuous or recurrent inflammatory
      disease of the pancreas characterized by progressive and irreversible
      morphological changes. It typically causes pain and permanent impairment of
      pancreatic function. In chronic pancreatitis areas of focal necrosis are followed
      by perilobular and intralobular fibrosis of the parenchyma, by stone formation in
      the pancreatic duct, calcifications in the parenchyma as well as the formation of
      pseudocysts. Late in the course of the disease a progressive loss of endocrine
      and exocrine function occurs. Despite advances in understanding the pathogenesis
      no causal treatment for chronic pancreatitis is presently available. Thus, there
      is a need for well characterized animal models for further investigations that
      allow translation to the human situation. This review summarizes existing
      experimental models and distinguishes them according to the type of pathological
      stimulus used for induction of pancreatitis. There is a special focus on
      pancreatic duct ligation, repetitive overstimulation with caerulein and chronic
      alcohol feeding. Secondly, attention is drawn to genetic models that have
      recently been generated and which mimic features of chronic pancreatitis in man.
      Each technique will be supplemented with data on the pathophysiological
      background of the model and their limitations will be discussed.

PMID- 22133270
TI  - Oxidized pectin cross-linked carboxymethyl chitosan: a new class of hydrogels.
AB  - Oxidation of pectin was performed with sodium periodate to prepare pectin
      dialdehyde (PD). In this study we used the cross-linking reaction of the active
      aldehyde of PD and the amino of carboxymethyl chitosan (CMC) to prepare the
      hydrogels. By controlling the proportion of pectin dialdehyde and CMC we made
      different kinds of hydrogels. We systematically studied the characters of the
      hydrogels using Fourier transform infrared spectroscopy analysis of the pectin
      dialdehyde, CMC and the hydrogels, and also X-ray diffractometry and scanning
      electron microscopy analysis of the instrument of the hydrogels. Equilibrium
      swelling showed that the gels retained about 88-93% water. The water vapor
      transmission rate (WVTR) and the evaporation of water from gels showed that such
      hydrogels were optimal for maintaining a moist environment conducive for wound
      healing. Examination of the hemolytic potential showed that the hydrogels were
      nonhemolytic in nature. The hydrogels were non-toxic and blood-compatible. This
      hydrogel prepared from oxidized pectin and CMC without employing any extraneous
      cross-linking agents is expected to have potential as wound-dressing material. 

PMID- 22133271
TI  - Model for adsorption of ligands to colloidal quantum dots with concentration
      dependent surface structure.
AB  - A study of the adsorption equilibrium of solution-phase CdS quantum dots (QDs)
      and acid-derivatized viologen ligands (N-[1-heptyl],N'-[3-carboxypropyl]-4,4'
      bipyridinium dihexafluorophosphate, V(2+)) reveals that the structure of the
      surfaces of the QDs depends on their concentration. This adsorption equilibrium
      is monitored through quenching of the photoluminescence of the QDs by V(2+) upon
      photoinduced electron transfer. When modeled with a simple Langmuir isotherm, the
      equilibrium constant for QD-V(2+) adsorption, K(a), increases from 6.7 * 10(5) to
      8.6 * 10(6) M(-1) upon decreasing the absolute concentration of the QDs from 1.4
      * 10(-6) to 5.1 * 10(-8) M. The apparent increase in K(a) upon dilution results
      from an increase in the mean number of available adsorption sites per QD from 1.1
      (for [QD] = 1.4 * 10(-6) M) to 37 (for [QD] = 5.1 * 10(-8) M) through desorption
      of native ligands from the surfaces of the QDs and through disaggregation of
      soluble QD clusters. A new model based on the Langmuir isotherm that treats both
      the number of adsorbed ligands per QD and the number of available binding sites
      per QD as binomially distributed quantities is described. This model yields a
      concentration-independent value for K(a) of 8.7 * 10(5) M(-1) for the QD-V(2+)
      system and provides a convenient means for quantitative analysis of QD-ligand
      adsorption in the presence of competing surface processes.

PMID- 22133273
TI  - Fondaparinux - data on efficacy and safety in special situations.
AB  - New anticoagulants promise to have better efficacy, more safety and/or a better
      manageability than traditional anticoagulants. However, knowledge is limited
      regarding special situations such as renal insufficiency, obesity, pregnancy,
      long-term therapy, heparin-induced thrombocytopenia, treatment in patients with
      mechanical heart valves, use for children, and in patients with a high risk of
      thromboembolic complications. These situations have rarely or even never been the
      objective of randomised controlled trials. The purpose of the present article is
      to summarize and discuss available data on efficacy and safety in these special
      situations for one of the first new anticoagulants, the indirect factor-Xa
      inhibitor fondaparinux. Furthermore, we discuss safety in licensed indications
      and management of bleeding complications and comment on measuring of drug
      concentration in plasma.

PMID- 22133272
TI  - Thrombolytic efficacy of tissue plasminogen activator-loaded echogenic liposomes
      in a rabbit thrombus model.
AB  - INTRODUCTION: Ultrasound (US)-enhanced thrombolytic treatment protocols currently
      in clinical trials for stroke applications involve systemic administration of
      tissue plasminogen activator (tPA; Alteplase), which carries a risk of adverse
      bleeding events. The present study aimed to compare the thrombolytic efficacy of
      a tPA-loaded echogenic liposome (ELIP) formulation with insonification protocols
      causing rapid fragmentation or acoustically-driven diffusion. MATERIALS AND
      METHODS: Thrombi were induced in the abdominal aortas of male New Zealand white
      rabbits (2-3kg) using thrombin and a sclerosing agent (sodium ricinoleate) after
      aortic denudation with a balloon catheter. Thrombolytic and cavitation nucleation
      agents (200MUg of tPA alone, tPA mixed with 50MUg of a microbubble contrast
      agent, or tPA-loaded ELIP) were bolus- injected proximal to the clot through a
      catheter introduced into the abdominal aorta from the carotid artery. Clots were
      exposed to transabdominal color Doppler US (6MHz) for 30 minutes at a low
      mechanical index (MI=0.2) to induce sustained bubble activity (acoustically
      driven diffusion), or for 2 minutes at an MI of 0.4 to cause ELIP fragmentation.
      Degree of recanalization was determined by Doppler flow measurements distal to
      the clots. RESULTS: All treatments showed thrombolysis, but tPA-loaded ELIP was
      the most efficacious regimen. Both US treatment strategies enhanced thrombolytic
      activity over control conditions. CONCLUSIONS: The thrombolytic efficacy of tPA
      loaded ELIP is comparable to other clinically described effective treatment
      protocols, while offering the advantages of US monitoring and enhanced
      thrombolysis from a site-specific delivery agent.

PMID- 22133274
TI  - Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal
      function and thrombocytopenia in Puumala hantavirus infection.
AB  - INTRODUCTION: Puumala virus (PUUV) infection is a viral hemorrhagic fever with
      renal syndrome (HFRS) characterized by thrombocytopenia and acute impairment of
      renal function. We aimed to assess whether genetic polymorphisms of platelet
      antigens together with those of von Willebrand factor (VWF) and plasminogen
      activator inhibitor (PAI-1) correlate with disease severity. Patients and methods
      172 consecutive hospital-treated patients with serologically confirmed acute PUUV
      infection were included. Platelet glycoprotein (GP) IIIa T>C (rs5918), GP Ia T>C
      (rs1126643), GP Ib C>T (rs6065), GP VI T>C (rs1613662), VWF A>G (rs1063856) and
      PAI-1 A>G (rs2227631) were genotyped. The associations of the rarer alleles with
      variables reflecting the severity of the disease were analyzed. RESULTS: PAI-1G
      carriers had higher maximum creatinine level compared with the non-carriers
      (median 213 MUmol/l, range 60-1499 MUmol/l vs. median 122 MUmol/l, range 51-1156
      MUmol/l, p = 0.01). The GG-genotypes had higher creatinine levels than GA- and AA
      genotypes (medians 249 MUmol/l, 204 MUmol/l and 122 MUmol/l, respectively, p =
      0.03). Polymorphisms of GP VI and VWF associated with lower creatinine levels
      during PUUV infection. The minor C-allele of GP Ia associated with lower platelet
      counts (median 44 * 10(9)/l, range 20-90 * 10(9)/l vs median 64 * 10(9)/l, range
      3-238 * 10(9)/l; p = 0.02). CONCLUSIONS: Polymorphism of PAI-1, a major regulator
      of fibrinolysis, has an adverse impact on the outcome of kidney function in PUUV
      HFRS. Platelet collagen receptor GP Ia polymorphism associates with lower
      platelet count.

PMID- 22133275
TI  - No effect of ethanol intake on thrombin generation parameters.

PMID- 22133276
TI  - Selective white matter abnormalities in a novel rat model of vascular dementia.
AB  - Rats subjected to bilateral common carotid artery (CCA) occlusion or 2-vessel
      occlusion (2VO) have been used as animal models of subcortical ischemic vascular
      dementia. However, this model possesses an inherent limitation in that cerebral
      blood flow (CBF) drops too sharply and substantially after ligation of CCAs. To
      circumvent such hypoxic-ischemic conditions, we tested implantation of the
      ameroid constrictor device on bilateral CCAs of male Wistar-Kyoto rats and more
      precisely replicated chronic cerebral hypoperfusion by gradual narrowing of the
      CCAs (2-vessel gradual occlusion; 2VGO). The acute cerebral blood flow reduction
      and resultant inflammatory responses observed in the 2VO rats were eliminated in
      the 2VGO rats. Thus, chronic cerebral hypoperfusion was segregated, and induced
      selective white matter changes with relatively preserved neurovascular coupling
      and substantially less metabolic and histological derangements in the gray matter
      including the hippocampus. This led to significant spatial working memory
      impairment of a magnitude similar to the 2VO rats at 28 days postoperation. The
      2VGO model may more closely mimic cognitive impairment subsequent to selective
      white matter damage.

PMID- 22133277
TI  - Pitavastatin decreases tau levels via the inactivation of Rho/ROCK.
AB  - Epidemiological studies have shown that long-term treatment with statins
      decreases the risk of developing Alzheimer's disease. Statins have pleiotropic
      effects by lowering the concentration of isoprenoid intermediates. Although
      several studies have shown that statins may reduce amyloid beta protein levels,
      there have been few reports on the interaction between statins and tau. We report
      here that pitavastatin reduces total and phosphorylated tau levels in a cellular
      model of tauopathy, and in primary neuronal cultures. The decrease caused by
      pitavastatin is reversed by the addition of mevalonate, or geranylgeranyl
      pyrophosphate. The maturation of small G proteins, including RhoA was disrupted
      by pitavastatin, as was the activity of glycogen synthase kinase 3beta
      (GSK3beta), a major tau kinase. Toxin A, inhibitor of glycosylation of small G
      proteins, and Rho kinase (ROCK) inhibitor decreased phosphorylated tau levels.
      Rho kinase inhibitor also inactivated glycogen synthase kinase 3beta. Although
      the mechanisms responsible for the reduction in tau protein by pitavastatin
      require further examination, this report sheds light on possible therapeutic
      approaches to tauopathy.

PMID- 22133278
TI  - Amyloid-beta oligomers stimulate microglia through a tyrosine kinase dependent
      mechanism.
AB  - Alzheimer's disease (AD) has been well characterized by the presence of reactive
      microglia, often associated with beta-amyloid (Abeta) plaque deposition. The
      oligomeric form of Abeta peptide (Abeta(o)) has neurotoxic effects in the
      presence of microglia and is suggested to potentiate proinflammatory changes in
      microglia in AD. Primary murine microglia cultures stimulated with Abeta(o)
      displayed increased protein phosphotyrosine and secreted tumor necrosis factor
      (TNF)-alpha levels which were attenuated by the Src/Abl inhibitor, dasatinib.
      Intracerebroventricular infusions of Abeta(o) into C57BL6/J mice stimulated
      increased microgliosis and protein phosphotyrosine levels that were also
      attenuated by dasatinib administration. The rodent findings were validated in
      human AD brains versus age-matched controls demonstrating reactive microglial
      association with Abeta(o) deposits and increased microglial protein
      phosphotyrosine and phospho-Src levels. These data suggest a role for Abeta(o) in
      microglial activation through a tyrosine kinase-dependant pathway both in rodent
      models and human disease. Use of a selective nonreceptor tyrosine kinase
      inhibitor such as dasatinib to attenuate microglial-dependent proinflammatory
      changes may prove to be an important step toward developing anti-inflammatory
      treatments for AD.

PMID- 22133279
TI  - Plasma reactive oxygen species levels are correlated with severity of age-related
      hearing impairment in humans.
AB  - To investigate the relationship between plasma reactive oxygen species (ROS)
      levels and severity of age-related hearing impairment in humans. We recruited 302
      adult subjects aged 40-77 years with normal or symmetrical sensorineural hearing
      loss. The association of plasma ROS levels on pure tone average of low
      frequencies (PTA-low) and pure tone average of high frequencies (PTA-high) were
      analyzed. Luminol-dependent chemiluminescence signals, which reflect hydrogen
      peroxide (H(2)O(2)), hypochlorite (HOCl/OCl(-)) and hydroxyl radicals (*OH)
      levels, showed significant positive association with PTA-low and PTA-high after
      adjusting for age, gender, central obesity, systemic diseases, and health-related
      habits (smoking, drinking, antioxidant intake). Lucigenin-dependent
      chemiluminescence signals, which mainly reflect superoxide anion (O(2)*(-))
      levels, showed significant positive association with PTA-low, but not with PTA
      high after adjusting for other variables. We concluded that plasma ROS levels
      were associated with severity of age-related hearing impairment in humans.
      Various ROS may differently affect auditory dysfunctions.

PMID- 22133280
TI  - Impact of chronic Helicobacter pylori infection on Alzheimer's disease:
      preliminary results.
AB  - Recent case-control studies reported an association between H. pylori infection
      and Alzheimer's disease (AD). Our aim was to compare cognitive impairment,
      neuroinflammation, and cerebrovascular lesion load in a group of AD patients
      according to their H. pylori status. For the 53 AD patients included, we
      assessed: clinical data (vascular comorbidities and cognitive assessment),
      biological data (especially fibrinogen, homocysteine levels, apolipoprotein E4
      genotype; cerebrospinal fluid [CSF] total tau protein [Tau], phospho-tau(181)
      protein [pTau(181)]), and amyloid beta peptide levels, serum/CSF-cytokines
      (interleukin [IL]-1beta, IL-6, IL-8, tumor necrosis factor [TNF]-alpha) and
      pepsinogen I/pepsinogen II (PgI/PgII) ratio, and cerebrovascular lesion load
      (magnetic resonance imaging [MRI] fluid-attenuated inversion recovery [FLAIR]
      with the Fazekas and Schmidt scale). H. pylori infection was diagnosed by enzyme
      linked immunosorbent assay (ELISA) and immunoblot test. H. pylori infection was
      associated with a decreased Mini Mental State Examination (MMS) (p = 0.024), and
      higher CSF pTau(181) (p = 0.014) and tau (p = 0.021) levels. A decreased PgI/II
      ratio (i.e., an increased gastric atrophy) was associated with the infection (p =
      0.005). Homocysteine levels were positively correlated to Fazekas score (r =
      0.34; p = 0.032) and to H. pylori immunoglobulin (Ig)G levels (r = 0.44; p =
      0.001). Higher CSF cytokine levels (IL-8, p = 0.003; TNF-alpha, p = 0.019) were
      associated with the infection, but systemic inflammation results were
      controversial. Finally, in multivariate analysis, a lower MMSE score (odds ratio
      [OR], 0.83 [0.72-0.97]; p = 0.017), plasma IL-1beta level (OR, 0.31 [0.11-0.87];
      p = 0.025), an increased gastric atrophy, i.e., a lower PgI/PgII ratio (OR, 0.63
      [0.43-0.93]; p = 0.020) were still associated with the infection. AD patients
      infected by H. pylori tended to be more cognitively impaired. Studies are needed
      to attest to the impact of H. pylori infection on AD course, especially on
      cerebrovascular lesions and neuroinflammation.

PMID- 22133281
TI  - A potential test system for detecting contaminations by bacterial lipoproteins.
AB  - Biological specimens are often contaminated with bacteria-derived products such
      as LPS or lipoproteins (LP), which trigger unwanted inflammatory responses in
      hosts. Whereas a contamination by LPS can be determined by various test systems,
      a contamination by LP can as yet not be determined. TLR4 and TLR2 are key
      components of the LPS and the LP receptor complex, respectively. It was tested in
      this study whether HEK293 cell stably transfected with bovine TLR2 have the
      ability to react to low concentrations of diacylated and triacylated synthetic
      LP. The stable cell lines we present here recognize low concentrations of
      synthetic LP resembling LP of different bacteria. Therefore, these cells are
      suitable to detect low contaminations present in probes. For example, HEK293
      cells stably transfected with bovine TLR2 recognized an egg albumin preparation
      as contaminated, as evidenced by copious production of IL-8. In contrast, these
      cells did not respond to a highly purified human serum albumin (HSA) preparation
      used in the clinic but responded to HSA containing small amounts of diacylated
      synthetic LP. The TLR4 ligand LPS is often said to activate TLR2. Here we present
      evidence that LP contaminations are responsible for TLR2 activity. HEK293 cells
      stably transfected with bovine TLR2 and TLR1 (e.g. clone 1) did not respond to
      ultra-pure Escherichia coli LPS preparations but acquired responsiveness when
      stimulated with differently purified commercial LPS. Thus, the described system
      involving HEK293 cells stably transfected with bovine TLR2 and TLR1 is the first
      test system described attempting to measure a contamination by LP.

PMID- 22133282
TI  - Aliskiren reduces portal pressure in cirrhotic rats.

PMID- 22133283
TI  - Child and adolescent mental health care in Dutch general practice: time trend
      analyses.
AB  - BACKGROUND: Because most children and adolescents visit their general
      practitioner (GP) regularly, general practice is a useful setting in which child
      and adolescent mental health problems can be identified, treated or referred to
      specialised care. Measures to strengthen Dutch primary mental health care have
      stimulated cooperation between primary and secondary mental health care and have
      led to an increase in the provision of social workers and primary care
      psychologists. These measures may have affected GPs' roles in child and
      adolescent mental health care. This study aims to investigate the identification
      and treatment of child and adolescent mental health problems in general practice
      over a five-year period (2004-2008). METHODS: Data of patients aged 0-18 years (N
      ranging from 37716 to 73432) were derived from electronic medical records of 42
      82 Dutch general practices. Time trends in the prevalence of recorded mental
      health problems, prescriptions for psychotropic medication, and referrals to
      primary and secondary mental health care were analysed. RESULTS: In 2008, 6.6% of
      children and 7.5% of adolescents were recorded as having mental health problems;
      15.2% of these children and 29.4% of these adolescents were prescribed
      psychotropic medication; 18.9% of these children and 22.9% of these adolescents
      were referred, mainly to secondary mental health care. Between 2004 and 2008, the
      percentages of children (chi-square: 22.06; p < 0.001) and adolescents (chi
      square: 9.15; p = 0.003) who were diagnosed with mental health problems
      increased. An increase was also found in the percentage of children who were
      prescribed psychostimulants (chi-square: 8.29; p = 0.004). Prescriptions for
      antidepressants decreased over time in both age groups (children: chi-square:
      6.80; p = 0.009; adolescents: chi-square: 13.52; p < 0.001). The percentages of
      children who were referred to primary (chi-square: 6.98; p = 0.008) and secondary
      mental health care (chi-square: 5.76; p = 0.02) increased over the years, whereas
      no significant increase was found for adolescents. CONCLUSIONS: Although GPs'
      identification of mental health problems and referrals to primary mental health
      care have increased, most referrals are still made to secondary care. To further
      strengthen primary mental health care, effective short-term interventions for
      child and adolescent mental health problems that can be applied in general
      practice need to be developed.

PMID- 22133284
TI  - Nickel-thiolate complex catalyst assembled in one step in water for solar H2
      production.
AB  - We report the use of a simple complex assembled from Ni(II) salt and 2
      mecaptoethanol in one step in water as the efficient catalyst in a molecular
      hydrogen system which can be sensitized by a low-cost xanthene dye, Erythrosin B.
      An excellent quantum efficiency of 24.5% is attained at 460 nm. This simple
      system is expected to contribute toward the development of economical and
      environmentally benign solar hydrogen production systems.

PMID- 22133285
TI  - MR phase imaging: sensitive and contrast-enhancing visualization in cellular
      imaging.
AB  - The successful translation of stem-cell therapies requires a detailed
      understanding of the fate of transplanted cells. Magnetic resonance imaging (MRI)
      has provided a noninvasive means of imaging cell dynamics in vivo by prelabeling
      cell with T(2) shortening iron oxide particles. However, this approach suffers
      from a gradual loss of sensitivity since active cell mitosis could decrease the
      cellular contrast agent (CA) concentration below detection level. In addition,
      the interpretation of images may be confounded by hypointensities induced by
      factors other than this CA susceptibility effect (CASE). We therefore examined
      the feasibility of exploiting the phase information in MRI to increase the
      sensitivity of cellular imaging and to differentiate the CASE from endogenous
      image hypointensity. Phase aliasing and the B(0) field inhomogeneity effect were
      removed by applying a reliable unwrapping algorithm and a high-pass filter,
      respectively, thus delineating phase variations originating from high spatial
      frequencies due to the CASE. We found that the filtered phase map detects labeled
      cells with high sensitivity and can readily differentiate the cell migration
      track from the white matter, both of which are hypointense in T(2)-weighted
      magnitude images. Furthermore, an approximate fivefold contrast-to-noise ratio
      enhancement can be achieved with an MRI phase map over conventional T(2)-weighted
      magnitude images.

PMID- 22133286
TI  - Multispectral MR images segmentation based on fuzzy knowledge and modified seeded
      region growing.
AB  - Magnetic resonance imaging (MRI) is a valuable diagnostic tool in medical science
      due to its capability for soft-tissue characterization and three-dimensional
      visualization. One potential application of MRI in clinical practice is brain
      parenchyma classification and segmentation. Based on fuzzy knowledge and modified
      seeded region growing, this work proposes a novel image segmentation method,
      called Fuzzy Knowledge-Based Seeded Region Growing (FKSRG), for multispectral MR
      images. In this work, fuzzy knowledge includes the fuzzy edge, fuzzy similarity
      and fuzzy distance, which are obtained from relationships between pixels in
      multispectral MR images and are applied to the modified seeded regions growing
      process. In conventional regions merging, the final number of regions is unknown.
      Therefore, a Target Generation Process is proposed and applied to support
      conventional regions merging, such that the FKSRG method does not over- or
      undersegment images. Finally, two image sets, namely, computer-generated phantom
      images and real MR images, are used in experiments to assess the effectiveness of
      the proposed FKSRG method. Experimental results demonstrate that the FKSRG method
      segments multispectral MR images much more effectively than the Functional MRI of
      the Brain Automated Segmentation Tool, K-means and Support Vector Machine
      methods.

PMID- 22133287
TI  - Mapping of muscle deformation during heating: in situ dynamic MRI and nonlinear
      registration.
AB  - We present developments in dynamic magnetic resonance imaging that allow internal
      structural muscle markers to be followed during heating. This monitoring is based
      on quantitative characterization of the experimental conditions and their
      temperature time course. A nonlinear image registration technique was optimized
      and applied to consecutively acquired images to measure the deformation fields in
      the muscle. A model coupling local deformation and temperature was obtained,
      which for the first time takes into account the variations of deformation and
      temperature in the sample. This modeling opens the way to a better understanding
      of the mechanisms responsible for mass loss and degradation of the textural
      properties of muscle during heating.

PMID- 22133288
TI  - The clinical application of whole-body diffusion-weighted imaging in the early
      assessment of chemotherapeutic effects in lymphoma: the initial experience.
AB  - At present, accurate assessment of therapeutic efficacy at the early stage of
      treatment is still a challenge for radiologists. As a new non-radiation whole
      body imaging technology, Whole body-diffusion weighted imaging (WB-DWI) had shown
      promising application prospects in therapeutic assessment, which confirmed by
      many premier animal studies. Here we report that in the chemotherapeutic
      assessment of malignant non-Hodgkin's lymphoma, WB-DWI can not only detect the
      morphological change of solid infiltrated lesion as the convention (such as CT,
      PET, etc.) but also provide information about the growth and decline process of
      tumor cells in the lesion combining with the dynamic changes of apparent
      diffusion coefficient (ADC) value, which is sooner than the morphological
      changes.

PMID- 22133289
TI  - Diffuse interstitial lung disease linked to vandetanib.

PMID- 22133290
TI  - Systematic review of the cost-effectiveness of positron-emission tomography in
      staging of non--small-cell lung cancer and management of solitary pulmonary
      nodules.
AB  - Implementation of positron-emission tomography (PET) is variable depending on
      jurisdiction in part due to uncertainty about cost-effectiveness. Our objective
      was to perform a systematic review describing cost-effectiveness of PET in
      staging of non-small-cell lung cancer (NSCLC) and management of solitary
      pulmonary nodules (SPN). Systematic literature searches were conducted using
      separate search strategies for multiple databases. Our validity criteria included
      measurement of study quality by means of the validated Quality of Health Economic
      Studies (QHES) instrument. Metrics such as mean PET costs, median average cost
      savings per patient, incremental cost-effectiveness ratio based on life years
      saved and quality-adjusted life years were calculated. Eighteen studies met our
      inclusion criteria with average QHES scores > 75. Studies were primarily based on
      the national health insurance payer perspective from 10 different countries. Cost
      effectiveness was assessed primarily using decision-tree modeling and sensitivity
      analysis to determine the effects of changing variables on expected cost and life
      expectancy. After adjusting for currency exchange rates and inflation to 2010
      United States dollars, the mean cost of PET was $1478. The cost-effectiveness
      metrics used in these studies were variable depending on sensitivity and
      specificity of diagnostic tests used in the models, probability of malignancy,
      and baseline strategy. Despite observed study heterogeneity, the consensus of
      these studies conclude that the additional information gained from PET imaging in
      the staging of NSCLC and diagnosis of SPNs is worth the cost in context of proper
      medical indications.

PMID- 22133291
TI  - Epothilones in development for non--small-cell lung cancer: novel anti-tubulin
      agents with the potential to overcome taxane resistance.
AB  - Progress in the treatment of non-small-cell lung cancer (NSCLC) will require the
      introduction of new agents as well as better use of existing therapies. Targeted
      therapies are likely to have a profound effect on the treatment of NSCLC after
      identification of patients who are most likely to benefit. The epothilones are
      novel anti-tubulin agents derived from Sorangium cellulosum. beta III tubulin
      overexpression has been implicated as a mechanism of anti-tubulin resistance that
      can be overcome by epothilones. Several epothilones have advanced to clinical
      trials; ixabepilone (BMS247550, aza-epothilone B, Bristol-Myers Squibb, New York,
      NY), patupilone (EPO906, Novartis, Basel, Switzerland) and sagopilone (ZK-EPO, ZK
      219477, Schering AG, Berlin-Wedding, Germany) are currently in active
      development. Several of the epothilones, most notably ixabepilone, have
      demonstrated activity in lung cancer in phase I and II trials, including taxane
      resistant patients. Although a phase II study failed to show superior outcome in
      patients with beta III tubulin overexpression, other aspects of the epothilones
      argue for their continued development.

PMID- 22133292
TI  - The role of cyclin D1 expression and patient's survival in non-small-cell lung
      cancer: a systematic review with meta-analysis.
AB  - BACKGROUND: The role of cell-cycle protein cyclin D1 in lung cancer remains
      controversial. To clarify its impact on survival in non-small-cell lung cancer
      (NSCLC), we performed a meta-analysis on the currently available medial
      literature to quantitatively assess its role on survival of NSCLC according to
      cyclin D1 status. METHOD: Published studies that investigated the association
      between cyclin D1 expression and NSCLC survival were identified. Meta-analysis
      was performed by using a DerSimonian-Laird model. Funnel plot was used to
      investigate publication bias and sources of heterogeneity were identified by
      using meta-regression analysis. RESULT: A total of 24 studies with 2731 patients
      were evaluable for this meta-analysis. No statistical significance was found that
      cyclin D1 expression was associated with poor prognosis in NSCLC (hazard ratio
      1.08 [95% CI, 0.80-1.45]) without publication bias found. But there was
      significant heterogeneity present; meta-regression analysis was used to explore
      the sources of heterogeneity and revealed that the outcome of analysis was
      influenced by cutoff values and ethnicity. No difference between positive and
      negative studies on study quality assessment was present. CONCLUSION: The cyclin
      D1 expression is unlikely to be useful as a prognostic marker for NSCLC in
      clinical practice from current evidence. The conclusion should be confirmed by a
      large well-designed prospective study.

PMID- 22133293
TI  - Clinical significance of IGF1R expression in non-small-cell lung cancer.
AB  - BACKGROUND: The purpose of the current study was to clarify the clinical role of
      insulin-like growth factor receptor-1 (IGF1R) in NSCLC. PATIENTS AND METHODS:
      Tumor specimens were collected from 285 patients who underwent complete resection
      for adenocarcinoma (AD, n = 182), squamous cell carcinoma (SCC, n = 77), and
      other histologic types of cancer (n = 26) of the lung. The expression of IGF1R
      and Ki-67 was evaluated by immunohistochemical (IHC) analysis. RESULTS: Positive
      expression of IGF1R was detected in 87 (30.5%) of 285 cases, of which 43 (23.6%)
      of 182 cases were AD, 36 (46.8%) of 77 cases were SCC, and 8 (30.8%) of 26 cases
      were other histologic types (SCC vs. AD, p < .001; SCC vs. non-SCC, p < .001).
      Positive IGF1R expression was also identified in 20 (44.4%) and 67 (27.9%) of the
      patients with and without recurrence, respectively (p = .027). Multivariate
      logistic regression models indicated that positive staining for IGF1R expression
      was an independent factor in AD associated with tumor recurrence (p = .040) but
      not in NSCLC, SCC, and other types of cancer. A positive IGF1R expression tended
      to demonstrate a poor disease-free survival (DFS) in NSCLC according to the
      Kaplan-Meier DFS curves (p = .053). The tumors showing a positive expression of
      IGF1R were observed more frequently in tumors with a positive expression of Ki-67
      than in the tumors with a negative expression of Ki-67 (p = .010). CONCLUSION:
      IGF1R expression was associated with reduced DFS correlating with postoperative
      recurrence. In addition, a significant relationship was also observed between
      IGF1R and Ki-67 expression in NSCLC. However, in subgroup analysis, a significant
      correlation was not observed. IGF1R expression predicts postoperative recurrence
      in patients with AD, but not in those with non-AD of NSCLC.

PMID- 22133294
TI  - Anatomical study of the pelvis in patients with adolescent idiopathic scoliosis.
AB  - Standing posterior-anterior (PA) radiographs from our clinical practice show that
      the concave and convex ilia are not always symmetrical in patients with
      adolescent idiopathic scoliosis (AIS). Transverse pelvic rotation may explain
      this observation, or pelvic asymmetry may be responsible. The present study
      investigated pelvic symmetry by examining the volume and linear measurements of
      the two hipbones in patients with AIS. Forty-two female patients with AIS were
      recruited for the study. Standing PA radiographs (covering the thoracic and
      lumbar spinal regions and the entire pelvis), CT scans and 3D reconstructions of
      the pelvis were obtained for all subjects. The concave/convex ratio of the
      inferior ilium at the sacroiliac joint medially (SI) and the anterior superior
      iliac spine laterally (ASIS) were measured on PA radiographs. Hipbone volumes and
      several distortion and abduction parameters were measured by post-processing
      software. The concave/convex ratio of SI-ASIS on PA radiographs was 0.97, which
      was significantly < 1 (P < 0.001). The concave and convex hipbone volumes were
      comparable in patients with AIS. The hipbone volumes were 257.3 +/- 43.5 cm(3)
      and 256.9 +/- 42.6 cm(3) at the concave and convex sides, respectively (P >
      0.05). Furthermore, all distortion and abduction parameters were comparable
      between the convex and concave sides. Therefore, the present study showed that
      there was no pelvic asymmetry in patients with AIS, although the concave/convex
      ratio of SI-ASIS on PA radiographs was significantly < 1. The clinical phenomenon
      of asymmetrical concave and convex ilia in patients with AIS in preoperative
      standing PA radiographs may be caused by transverse pelvic rotation, but it is
      not due to developmental asymmetry or distortion of the pelvis.

PMID- 22133295
TI  - Saponins from the traditional medicinal plant Momordica charantia stimulate
      insulin secretion in vitro.
AB  - The antidiabetic activity of Momordica charantia (L.), Cucurbitaceae, a widely
      used treatment for diabetes in a number of traditional medicine systems, was
      investigated in vitro. Antidiabetic activity has been reported for certain
      saponins isolated from M. charantia. In this study insulin secretion was measured
      in MIN6 beta-cells incubated with an ethanol extract, saponin-rich fraction, and
      five purified saponins and cucurbitane triterpenoids from M. charantia,
      3beta,7beta,25-trihydroxycucurbita-5,23(E)-dien-19-al (1), momordicine I (2),
      momordicine II (3), 3-hydroxycucurbita-5,24-dien-19-al-7,23-di-O-beta
      glucopyranoside (4), and kuguaglycoside G (5). Treatments were compared to
      incubation with high glucose (27 mM) and the insulin secretagogue, glipizide (50
      MUM). At 125 MUg/ml, an LC-ToF-MS characterized saponin-rich fraction stimulated
      insulin secretion significantly more than the DMSO vehicle, p=0.02. At
      concentrations 10 and 25 MUg/ml, compounds 3 and 5 also significantly stimulated
      insulin secretion as compared to the vehicle, p<=0.007, and p=0.002,
      respectively. This is the first report of a saponin-rich fraction, and isolated
      compounds from M. charantia, stimulating insulin secretion in an in vitro, static
      incubation assay.

PMID- 22133296
TI  - Expression of COX-2 and E-cadherin in Tunisian patients with colorectal
      adenocarcinoma.
AB  - Cyclo-oxygenase 2 (COX-2) and E-cadherin are promising biomarkers for cancer
      diagnosis and therapy. The aim of this study was to examine the expression of
      these two proteins in primary colorectal adenocarcinomas and to investigate their
      association with clinicopathological characteristics including survival of
      patients. Immunostaining of E-cadherin and COX-2 was assessed in 70 primary
      colorectal adenocarcinomas from Tunisian patients. Membranous E-cadherin
      immunostaining and cytoplasmic COX-2 expression were observed in 74.3% and 68.6%
      of cases respectively. A significant association was found between COX-2
      expression and age at diagnosis (P=0.02), and vessel invasion (P=0.037). The
      expression of E-cadherin correlated with age at diagnosis (P=0.01), and tumor
      size (P=0.02). In addition, by multivariate analysis, we revealed a significant
      association with 1-year disease free survival and a tendency with distant
      metastasis (P=0.017 and P=0.065 respectively). On the other hand, tumors
      exhibiting COX-2+/E-cadherin-profile were larger (P=0.006), and in an advanced
      stage (P=0.001). Survival analysis showed that COX-2 over-expression confers a
      reduced overall survival rate (Plog rank=0.036) and is an independent factor
      predictive for prognosis.

PMID- 22133297
TI  - Prognostic factors in definitive radiochemotherapy of advanced inoperable
      esophageal cancer.
AB  - The aim of this study was to assess the efficacy and prognostic factors of
      definitive radiochemotherapy (RCT) for inoperable esophageal cancer. Between 1995
      and 2005 all patients with inoperable esophageal cancer that underwent concurrent
      RCT were included in this retrospective study. Conventional computed tomography
      based treatment planning as well as 3D-conformal radiotherapy (RT) was used.
      Maximum radiotherapy dose was 63 Gy. Chemotherapy consisted of cisplatin (20
      mg/m(2) d1-5 and 29-33) and 5-FU (650-1000 mg/m(2) d1-5 and 29-33). Patients not
      suitable for RCT received radiotherapy alone. Toxicity was measured according to
      common toxicity criteria (CTC). Two hundred three consecutive patients with
      inoperable esophageal cancer that received definitive therapy were identified in
      this time period (160 with squamous cell carcinoma and 43 with adenocarcinoma).
      The 2-year overall survival probability was 21.2% whereas the progression-free
      survival at 2 years was 13.8% for all patients. In the univariate analysis, type
      of histology, T-stage, N-stage, application of chemotherapy, and the radiation
      dose were significantly correlated with overall/progression-free survival.
      Moreover, multivariate analysis revealed an independent prognostic impact for N
      stage, radiation dose, and concurrent chemotherapy. Definitive RCT is an
      important palliative treatment option for patients with inoperable esophageal
      cancer. N-stage, radiation dose, and concurrent chemotherapy are important
      prognostic factors for survival.

PMID- 22133299
TI  - IgG N-glycans as potential biomarkers for determining galactose tolerance in
      Classical Galactosaemia.
AB  - N-glycan processing and assembly defects have been demonstrated in untreated and
      partially treated patients with Classical Galactosaemia. These defects may
      contribute to the ongoing pathophysiology of this disease. The aim of this study
      was to develop an informative method of studying differential galactose tolerance
      levels and diet control in individuals with Galactosaemia, compared to the
      standard biochemical markers. Ten Galactosaemia adults with normal intellectual
      outcomes were analyzed in the study. Five subjects followed galactose
      liberalization, increments of 300 mg to 4000 mg/day over 16 weeks, and were
      compared to five adult Galactosaemia controls on a galactose restricted diet. All
      study subjects underwent clinical and biochemical monitoring of red blood cell
      galactose-1-phosphate (RBC Gal-1-P) and urinary galactitol levels. Serum N
      glycans were isolated and analyzed by normal phase high-performance liquid
      chromatography (NP-HPLC) with galactosylation of IgG used as a specific biomarker
      of galactose tolerance. IgG N-glycan profiles showed consistent individual
      alterations in response to diet liberalization. The individual profiles were
      improved for all, but one study subject, at a galactose intake of 1000 mg/day,
      with decreases in agalactosylated (G0) and increases in digalactosylated (G2) N
      glycans. We conclude that IgG N-glycan profiling is an improved method of
      monitoring variable galactosylation and determining individual galactose
      tolerance in Galactosaemia compared to the standard methods.

PMID- 22133298
TI  - Preclinical evaluation of a clinical candidate AAV8 vector for ornithine
      transcarbamylase (OTC) deficiency reveals functional enzyme from each persisting
      vector genome.
AB  - Ornithine transcarbamylase deficiency (OTCD), the most common and severe urea
      cycle disorder, is an excellent model for developing liver-directed gene therapy.
      No curative therapy exists except for liver transplantation which is limited by
      available donors and carries significant risk of mortality and morbidity. Adeno
      associated virus 8 (AAV8) has been shown to be the most efficient vector for
      liver-directed gene transfer and is currently being evaluated in a clinical trial
      for treating hemophilia B. In this study, we generated a clinical candidate
      vector for a proposed OTC gene therapy trial in humans based on a self
      complementary AAV8 vector expressing codon-optimized human OTC (hOTCco) under the
      control of a liver-specific promoter. Codon-optimization dramatically improved
      the efficacy of OTC gene therapy. Supraphysiological expression levels and
      activity of hOTC were achieved in adult spf(ash) mice following a single
      intravenous injection of hOTCco vector. Vector doses as low as 1*10(10) genome
      copies (GC) achieved robust and sustained correction of the OTCD biomarker orotic
      aciduria and clinical protection against an ammonia challenge. Functional
      expression of hOTC in 40% of liver areas was found in mice treated with a low
      vector dose of 1*10(9) GC. We suggest that the clinical candidate vector we have
      developed has the potential to achieve therapeutic effects in OTCD patients.

PMID- 22133300
TI  - Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania
      and Estonia.
AB  - Mucopolysaccharidosis VI (MPS VI) is a rare autosomal recessive disorder caused
      by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB). Over 130 ARSB gene
      mutations have been identified thus far and most mutations are unique to
      individual families. We aimed to analyze the spectrum of mutations in the ARSB
      gene responsible for the disorder in Poland, Belarus and Baltic States. Twenty
      one families with MPS VI patients, in whom diagnosis was confirmed biochemically
      and enzymatically, were studied. Direct sequencing of patient genomic DNA was
      used to identify ARSB mutations. In total, fourteen different disease-causing
      mutations were found. Three novel mutations included insertion c.375_376insT, a
      missense mutation c.499G>A (p.G167R) and deletion/insertion
      c.750_754delinsCCTGAAGTCAAG. We also report 11 previously described mutations
      (p.A33V, p.W57C, p.Q88X, p.T92K, p.Q97X, p.R152W, p.R160Q, p.R160X, p.Y210C,
      p.Y266S, p.G302R). The mutation p.R152W was present at a high prevalence of 50%
      (21/42) the mutated alleles in this group of patients. High prevalence of p.R152W
      mutation in Poland, Belarus and Baltic States indicates a possible founder effect
      and suggests that screening for this mutation may be appropriate in MPS VI
      patients from this region. Our study has also provided evidence to support
      genotype-phenotype correlation.

PMID- 22133301
TI  - Differentially expressed angiogenic genes in diabetic erectile tissue - results
      from a microarray screening.
AB  - Diabetes-induced metabolic derangements promote endothelial malfunction,
      contributing to erectile dysfunction (ED). However, it remains unclear which
      angiogenic molecular mechanisms are deregulated in diabetic corpus cavernosum
      (CC). We investigated early and late alterations in cavernosal angiogenic gene
      expression associated to diabetes. Angiogenic changes were assessed in penile
      tissue of streptozotocin-induced Wistar rats, in an early (2-week) and
      established stage (8-week) of diabetes. Differentially expressed genes were
      identified by microarrays and expression data validated by quantitative real-time
      PCR (qrt-PCR). At protein level, quantitative immunohistochemistry confirmed the
      arrays data and dual immunofluorescence for selected alterations and alpha-smooth
      muscle actin (alpha-SMA) identified the cellular location of target proteins. The
      selected differentially expressed genes were also evaluated in human non-diabetic
      and diabetic CC by quantitative immunolabeling. At 2-week diabetes there was no
      differential gene expression between non-diabetic and diabetic CC. At 8-week, 10
      genes were found down-regulated in diabetics. The results were validated by qrt
      PCR for the insulin-like growth factor-1 (Igf1) and the natriuretic peptide
      receptor-1 (Npr1) genes. Dual immunofluorescence for IGF-1/ alpha-SMA showed
      predominant localization of IGF-1 in SM. NPR-1 expression was diffuse and mostly
      present in trabecular fibroblasts and SM. Quantitative immunostaining confirmed
      the decreased expression of both proteins in diabetic tissues. Concordantly, we
      detected a significant reduction in IGF-1 and NPR-1 protein expressions in human
      diabetic samples. Microarray analysis identified 10 angiogenic-related molecules
      deregulated in CC of established diabetes. Among them, IGF-1 and NPR-1 were
      significantly down-regulated and might result in preventive/therapeutic targets
      for ED management.

PMID- 22133302
TI  - Ethylmalonic acid impairs brain mitochondrial succinate and malate transport.
AB  - Tissue accumulation and high urinary excretion of ethylmalonic acid (EMA) occur
      in ethylmalonic encephalopathy (EE) and short chain acyl-CoA dehydrogenase
      deficiency (SCADD). Although these autosomal recessive disorders are clinically
      characterized by neurological abnormalities, the mechanisms underlying the brain
      damage are poorly known. Considering that little is known about the neurotoxicity
      of EMA and that hyperlacticacidemia occurs in EE and SCADD, we evaluated the
      effects of this metabolite on important parameters of oxidative metabolism in
      isolated rat brain mitochondria. EMA inhibited either ADP-stimulated or uncoupled
      mitochondrial respiration supported by succinate and malate, but not by glutamate
      plus malate. In addition, EMA mildly stimulated oxygen consumption by succinate
      respiring mitochondria in resting state. Methylmalonic acid (MMA), malonic acid
      (MA) and butylmalonic acid (BtMA) had a similar effect on ADP-stimulated or
      uncoupled respiration. Furthermore, EMA-, MMA- and BtMA-induced inhibitory
      effects on succinate oxidation were significantly minimized by nonselective
      permeabilization of the mitochondrial membranes by alamethicin, whereas MA
      inhibitory effect was not altered. In addition, MA was the only tested compound
      that reduced succinate dehydrogenase activity. We also observed that EMA markedly
      inhibited succinate and malate transport through the mitochondrial dicarboxylate
      carrier. Mitochondrial membrane potential was also reduced by EMA and MA, but not
      by MMA, using succinate as electron donor, whereas none of these compounds was
      able to alter the membrane potential using glutamate plus malate as electron
      donors. Taken together, our results strongly indicate that EMA impairs succinate
      and malate uptake through the mitochondrial dicarboxylate carrier.

PMID- 22133304
TI  - Theta modulation of inter-regional gamma synchronization during auditory
      attention control.
AB  - Synchronization of gamma oscillations among brain regions is relevant for
      dynamically organizing communication among neurons to support cognitive and
      perceptual processing, including attention orienting. Recent research has
      demonstrated that inter-regional synchronization in the gamma-band is modulated
      by theta rhythms during cortical processing. It has been proposed that such cross
      frequency dynamics underlie the integration of local processes into large-scale
      functional networks. To investigate the potential role of theta-gamma mechanisms
      during auditory attention control, we localized activated regions using EEG
      beamformer analysis, and calculated inter-regional gamma-band synchronization
      between activated regions as well as modulation of inter-regional gamma-band
      synchronization by the phase of cortical theta rhythms. Abundant synchronization
      of gamma-band oscillations among regions comprising the auditory attention
      control network was observed. This inter-regional gamma synchronization was
      modulated by theta phase. These results provide further evidence implicating
      inter-regional gamma-band synchronization, and theta-gamma interactions, in task
      dependent communication among cortical regions, and provide the first evidence
      that such mechanisms are relevant for auditory attention control.

PMID- 22133303
TI  - Identification of DNA methylation changes associated with human gastric cancer.
AB  - BACKGROUND: Epigenetic alteration of gene expression is a common event in human
      cancer. DNA methylation is a well-known epigenetic process, but verifying the
      exact nature of epigenetic changes associated with cancer remains difficult.
      METHODS: We profiled the methylome of human gastric cancer tissue at 50-bp
      resolution using a methylated DNA enrichment technique (methylated CpG island
      recovery assay) in combination with a genome analyzer and a new normalization
      algorithm. RESULTS: We were able to gain a comprehensive view of promoters with
      various CpG densities, including CpG Islands (CGIs), transcript bodies, and
      various repeat classes. We found that gastric cancer was associated with
      hypermethylation of 5' CGIs and the 5'-end of coding exons as well as
      hypomethylation of repeat elements, such as short interspersed nuclear elements
      and the composite element SVA. Hypermethylation of 5' CGIs was significantly
      correlated with downregulation of associated genes, such as those in the HOX and
      histone gene families. We also discovered long-range epigenetic silencing (LRES)
      regions in gastric cancer tissue and identified several hypermethylated genes
      (MDM2, DYRK2, and LYZ) within these regions. The methylation status of CGIs and
      gene annotation elements in metastatic lymph nodes was intermediate between
      normal and cancerous tissue, indicating that methylation of specific genes is
      gradually increased in cancerous tissue. CONCLUSIONS: Our findings will provide
      valuable data for future analysis of CpG methylation patterns, useful markers for
      the diagnosis of stomach cancer, as well as a new analysis method for clinical
      epigenomics investigations.

PMID- 22133305
TI  - A pilot study of the effects of cannabis on appetite hormones in HIV-infected
      adult men.
AB  - RATIONALE: The endocannabinoid system is under active investigation as a
      pharmacological target for obesity management due to its role in appetite
      regulation and metabolism. Exogenous cannabinoids such as tetrahydrocannabinol
      (THC) stimulate appetite and food intake. However, there are no controlled
      observations directly linking THC to changes of most of the appetite hormones.
      OBJECTIVES: We took the opportunity afforded by a placebo-controlled trial of
      smoked medicinal cannabis for HIV-associated neuropathic pain to evaluate the
      effects of THC on the appetite hormones ghrelin, leptin and PYY, as well as on
      insulin. METHODS: In this double-blind cross-over study, each subject was exposed
      to both active cannabis (THC) and placebo. RESULTS: Compared to placebo, cannabis
      administration was associated with significant increases in plasma levels of
      ghrelin and leptin, and decreases in PYY, but did not significantly influence
      insulin levels. CONCLUSION: These findings are consistent with modulation of
      appetite hormones mediated through endogenous cannabinoid receptors, independent
      of glucose metabolism.

PMID- 22133306
TI  - Orexin-1 receptor antagonism does not reduce the rewarding potency of cocaine in
      Swiss-Webster mice.
AB  - The orexin family of hypothalamic neuropeptides has been implicated in
      reinforcement mechanisms relevant to both food and drug reward. Previous
      behavioral studies with antagonists at the orexin A-selective receptor, OX(1),
      have demonstrated its involvement in behavioral sensitization, conditioned place
      preference, and self-administration of drugs of abuse. Adult male Swiss-Webster
      mice were implanted with stimulating electrodes to the lateral hypothalamus and
      trained to perform intracranial self-stimulation (ICSS). The effects of the OX(1)
      selective antagonist SB 334867 on brain stimulation-reward (BSR) and cocaine
      potentiation of BSR were measured. SB 334867 (10-30mg/kg, i.p.) alone had no
      effect on ICSS performance or BSR threshold. Cocaine (1.0-30mg/kgi.p.) dose
      dependently potentiated BSR, measured as lowering of BSR threshold. This effect
      was not blocked by 30mg/kg SB 334867 at any cocaine dose tested. In agreement
      with previous reports, SB 334867 resulted in a reduction of body weight 24h after
      acute administration. Based on these data, it is concluded that orexins acting at
      OX(1) do not contribute to BSR; and are not involved in the reward-potentiating
      actions of cocaine on BSR. The data are discussed in the context of prior
      findings of SB 334867 effects on drug-seeking and drug-consuming behaviors.

PMID- 22133307
TI  - Sigma-1 receptor agonists provide neuroprotection against gp120 via a change in
      bcl-2 expression in mouse neuronal cultures.
AB  - Although combined antiretroviral therapy has significantly improved the prognosis
      of HIV-1 infected patients and decreased the incidence of HIV-1 associated
      dementia, the cumulative prevalence of this disease, in particular, mild or
      asymptomatic neurocognitive impairment, has not decreased. Thus, in addition to
      active antiretroviral therapy, the search for an effective neuroprotective
      approach is very important. Sigma-1 receptors are widely distributed in the
      central nervous system. Sigma-1 receptor agonists are robustly neuroprotective in
      many neuropathy and neurotoxicity in vivo and in vitro studies. This study aims
      to investigate possible neuroprotective effects of sigma-1 receptor agonist, 4
      phenyl-1-(4-phenylbutyl) piperidine (PPBP) against HIV-1 protein gp120. Primary
      cortical neuronal cultures were exposed to gp120 in different concentrations; to
      investigate neuroprotective effects of sigma-1 receptor agonist, cells were pre
      treated with PPBP (10MUM) in the presence or absence of pre-incubated sigma-1
      receptor antagonist rimcazole (5MUM). Cell apoptosis was confirmed with
      calcein/PI uptake test, lactate dehydrogenase (LDH) leakage assay or TUNEL assay
      and neurite degeneration was evaluated with morphometry via MAP-2 stained
      immunofluorescence. The mRNA and protein levels of apoptosis associated bax and
      bcl-2 were determined with real-time qPCR and Western blot. The results showed
      that gp120 could induce neuronal apoptosis and neurite degeneration in a
      concentration dependent manner and PPBP could attenuate the neurotoxicity of
      gp120. Simultaneously, gp120 could induce low expression of bcl-2 and bax, but
      only low expression of bcl-2 could be reversed by PPBP. The present data suggest
      that PPBP, at least, in part protects the neuron against gp120 by regulating bcl
      2 expression.

PMID- 22133308
TI  - The combination of organoselenium compounds and guanosine prevents glutamate
      induced oxidative stress in different regions of rat brains.
AB  - This study was designed to investigate the protective effects of the combination
      of guanosine and 2 organoselenium compounds (ebselen and diphenyl diselenide)
      against glutamate-induced oxidative stress in different regions of rat brains.
      Glutamate caused an increase in reactive oxygen species (ROS) generation and a
      decrease in [(3)H]-glutamate uptake in striatal, cortical, and hippocampal
      slices. Guanosine, ebselen, and diphenyl diselenide prevented glutamate-induced
      ROS production in striatal, cortical and hippocampal slices. The combination of
      guanosine with organoselenium compounds was more effective against glutamate
      induced ROS production than the individual compounds alone. Guanosine prevented
      [(3)H]-glutamate uptake inhibition in striatal, cortical, and hippocampal slices.
      Thus, protection against the harmful effects of glutamate is possibly due to the
      combination of the antioxidant properties of organoselenium compounds and the
      stimulatory effect of guanosine on glutamate uptake. In conclusion, the
      combination of antioxidants and glutamatergic system modulators could be
      considered a potential therapy against the prooxidant effects of glutamate.

PMID- 22133309
TI  - Nitric oxide signaling in the retina: what have we learned in two decades?
AB  - Two decades after its first detection in the retina, nitric oxide (NO) continues
      to puzzle visual neuroscientists. While its liberation by photoreceptors remains
      controversial, recent evidence supports three subtypes of amacrine cells as main
      sources of NO in the inner retina. NO synthesis was shown to depend on light
      stimulation, and mounting evidence suggests that NO is a regulator of visual
      adaptation at different signal processing levels. NO modulates light responses in
      all retinal neuron classes, and specific ion conductances are activated by NO in
      rods, cones, bipolar and ganglion cells. Light-dependent gap junction coupling in
      the inner and outer plexiform layers is also affected by NO. The vast majority of
      these effects were shown to be mediated by activation of the NO receptor soluble
      guanylate cyclase and resultant cGMP elevation. This review analyzes the current
      state of knowledge on physiological NO signaling in the retina.

PMID- 22133310
TI  - Temperature can entrain egg laying rhythm of Drosophila but may not be a stronger
      zeitgeber than light.
AB  - In Drosophila multiple circadian oscillators and behavioral rhythms are known to
      exist, yet most previous studies that attempted to understand circadian
      entrainment have focused on the activity/rest rhythm and to some extent the adult
      emergence rhythm. Egg laying behavior of Drosophila females also follows
      circadian rhythmicity and has been seen to deviate substantially from the better
      characterized rhythms in a few aspects. Here we report the findings of our study
      aimed at evaluating how circadian egg laying rhythm in fruit flies Drosophila
      melanogaster entrains to time cues provided by light and temperature. Previous
      studies have shown that activity/rest rhythm of flies entrains readily to
      light/dark (LD) and temperature cycles (TC). Our present study revealed that egg
      laying rhythm of a greater percentage of females entrains to TC compared to LD
      cycles. Therefore, in the specific context of our study this result can be taken
      to suggest that egg laying clocks of D. melanogaster entrains to TC more readily
      than LD cycles. However, when TC were presented along with out-of-phase LD
      cycles, the rhythm displayed two peaks, one occurring close to lights-off and the
      other near the onset of low temperature phase, indicating that upon entrainment
      by TC, LD cycles may be able to exert a greater influence on the phase of the
      rhythm. These results suggest that temperature and light associatively entrain
      circadian egg laying clocks of Drosophila.

PMID- 22133311
TI  - Energetic consequences of repeated and prolonged dehydration in the Antarctic
      midge, Belgica antarctica.
AB  - Larvae of the Antarctic midge, Belgica antarctica, routinely face periods of
      limited water availability in their natural environments on the Antarctic
      Peninsula. As a result, B. antarctica is one of the most dehydration-tolerant
      insects studied, surviving up to 70% loss of its body water. While previous
      studies have characterized the physiological effects of a single bout of
      dehydration, in nature larvae are likely to experience multiple bouts of
      dehydration throughout their lifetime. Thus, we examined the physiological
      consequences of repeated dehydration and compared results to larvae exposed to a
      single, prolonged period of dehydration. For the repeated dehydration experiment,
      larvae were exposed to 1-5 cycles of 24 h dehydration at 75% RH followed by 24 h
      rehydration. Each bout of dehydration resulted in 30-40% loss of body water, with
      a concomitant 2- to 3-fold increase in body fluid osmolality. While nearly 100%
      of larvae survived a single bout of dehydration, <65% of larvae survived five
      such cycles. Larvae subjected to multiple bouts of dehydration also experienced
      severe depletion of carbohydrate energy reserves; glycogen and trehalose content
      decreased with each successive cycle, with larvae losing 89% and 48% of their
      glycogen and trehalose, respectively, after five cycles of
      dehydration/rehydration. Larvae exposed to prolonged dehydration (99% RH for 10d)
      had 26% less water, 43% less glycogen, and 27% less lipid content than controls,
      but did not experience any mortality. Thus, both repeated and prolonged
      dehydration results in substantial energetic costs that are likely to negatively
      impact fitness.

PMID- 22133312
TI  - The blowfly salivary gland - a model system for analyzing the regulation of
      plasma membrane V-ATPase.
AB  - Vacuolar H(+)-ATPases (V-ATPases) are heteromultimeric proteins that use the
      energy of ATP hydrolysis for the electrogenic transport of protons across
      membranes. They are common to all eukaryotic cells and are located in the plasma
      membrane or in membranes of acid organelles. In many insect epithelia, V-ATPase
      molecules reside in large numbers in the apical plasma membrane and create an
      electrochemical proton gradient that is used for the acidification or
      alkalinization of the extracellular space, the secretion or reabsorption of ions
      and fluids, the import of nutrients, and diverse other cellular activities. Here,
      we summarize our results on the functions and regulation of V-ATPase in the
      tubular salivary gland of the blowfly Calliphora vicina. In this gland, V-ATPase
      activity energizes the secretion of a KCl-rich saliva in response to the
      neurohormone serotonin (5-HT). Because of particular morphological and
      physiological features, the blowfly salivary glands are a superior and exemplary
      system for the analysis of the intracellular signaling pathways and mechanisms
      that modulate V-ATPase activity and solute transport in an insect epithelium.

PMID- 22133313
TI  - Functional analyses of the digestive beta-glucosidase of Formosan subterranean
      termites (Coptotermes formosanus).
AB  - The research was to elucidate the function of the beta-glucosidase of Formosan
      subterranean termites in vitro and in vivo. The gene transcript was detected
      predominantly in the salivary gland tissue, relative to the midgut and the
      hindgut of the foraging worker caste, indicating salivary glands were the major
      expression sites of the beta-glucosidase. Using recombinant beta-glucosidase
      produced in Escherichia coli, the enzyme showed higher affinity and activity
      toward cellobiose and cellotriose than other substrates tested. In assessing
      impacts of specific inhibitors, we found that the beta-glucosidase could be
      irreversibly inactivated by conduritol B epoxide (CBE) but not gluconolactone.
      Termite feeding assays showed that the CBE treatment reduced the glucose supply
      in the midgut and resulted in the body weight loss while no effect was observed
      for the gluconolactone treatment. These findings highlighted that the beta
      glucosidase is one of the critical cellulases responsible for cellulose
      degradation and glucose production; inactivation of these digestive enzymes by
      specific inhibitors may starve the termite.

PMID- 22133314
TI  - Dynamic disorder in single-enzyme experiments: facts and artifacts.
AB  - Using a single-molecule fluorescence approach, the time series of catalytic
      events of an enzymatic reaction can be monitored, yielding a sequence of
      fluorescent "on"- and "off"-states. An accurate on/off-assignment is complicated
      by the intrinsic and extrinsic noise in every single-molecule fluorescence
      experiment. Using simulated data, the performance of the most widely employed
      binning and thresholding approach was systematically compared to change point
      analysis. It is shown that the underlying on- and off-histograms as well as the
      off-autocorrelation are not necessarily extracted from the "signal'' buried in
      noise. The shapes of the on- and off-histograms are affected by artifacts
      introduced by the analysis procedure and depend on the signal-to-noise ratio and
      the overall fluorescence intensity. For experimental data where the background
      intensity is not constant over time we consider change point analysis to be more
      accurate. When using change point analysis for data of the enzyme alpha
      chymotrypsin, no characteristics of dynamic disorder was found. In light of these
      results, dynamic disorder might not be a general sign of enzymatic reactions.

PMID- 22133316
TI  - Enzymatic pretreatment for preparing starch nanocrystals.
AB  - Starch nanocrystals (SNCs) are crystalline platelets resulting from the acid
      hydrolysis of starch. A limiting factor for their more widespread use is their
      preparation duration. Therefore, this study investigates the possibility of
      developing an enzymatic pretreatment of starch to reduce the acid hydrolysis
      duration. A screening of three types of enzymes, namely, alpha-amylase, beta
      amylase, and glucoamylase, is proposed, and the latter was selected for a
      pretreatment. Compared with the regular kinetics of hydrolysis for preparing SNC,
      that of pretreated starch was much faster. The extent of hydrolysis normally
      reached in 24 h was obtained after only 6 h, and the regular final yield (15%
      after 5 days) was reached in 45 h. AFM and X-ray diffraction measurements
      confirmed that the obtained nanoparticles were indeed SNC.

PMID- 22133315
TI  - Maternal separation affects dopamine transporter function in the spontaneously
      hypertensive rat: an in vivo electrochemical study.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a developmental
      disorder characterised by symptoms of inattention, impulsivity and hyperactivity.
      The spontaneously hypertensive rat (SHR) is a well-characterised model of this
      disorder and has been shown to exhibit dopamine dysregulation, one of the
      hypothesised causes of ADHD. Since stress experienced in the early stages of life
      can have long-lasting effects on behaviour, it was considered that early life
      stress may alter development of the dopaminergic system and thereby contribute to
      the behavioural characteristics of SHR. It was hypothesized that maternal
      separation would alter dopamine regulation by the transporter (DAT) in ways that
      distinguish SHR from control rat strains. METHODS: SHR and control Wistar-Kyoto
      (WKY) rats were subjected to maternal separation for 3 hours per day from
      postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like
      behaviour followed by in vivo chronoamperometry to determine whether changes had
      occurred in striatal clearance of dopamine by DAT. The rate of disappearance of
      ejected dopamine was used as a measure of DAT function. RESULTS: Consistent with
      a model for ADHD, SHR were more active than WKY in the open field. SHR entered
      the inner zone more frequently and covered a significantly greater distance than
      WKY. Maternal separation increased the time that WKY spent in the closed arms and
      latency to enter the open arms of the elevated plus maze, consistent with other
      rat strains. Of note is that, maternal separation failed to produce anxiety-like
      behaviour in SHR. Analysis of the chronoamperometric data revealed that there was
      no difference in DAT function in the striatum of non-separated SHR and WKY.
      Maternal separation decreased the rate of dopamine clearance (k-1) in SHR
      striatum. Consistent with this observation, the dopamine clearance time (T100)
      was increased in SHR. These results suggest that the chronic mild stress of
      maternal separation impaired the function of striatal DAT in SHR. CONCLUSIONS:
      The present findings suggest that maternal separation failed to alter the
      behaviour of SHR in the open field and elevated plus maze. However, maternal
      separation altered the dopaminergic system by decreasing surface expression of
      DAT and/or the affinity of DAT for dopamine, increasing the time to clear
      dopamine from the extracellular fluid in the striatum of SHR.

PMID- 22133317
TI  - Asthma exacerbations: origin, effect, and prevention.
AB  - Asthma is the most common chronic respiratory disease, affecting up to 10% of
      adults and 30% of children in the Western world. Despite advances in asthma
      management, acute exacerbations continue to occur and impose considerable
      morbidity on patients and constitute a major burden on health care resources.
      Respiratory tract viruses have emerged as the most frequent triggers for
      exacerbations in both children and adults; however, the mechanisms underlying
      these remain poorly understood. More recently, it has become increasingly clear
      that interactions might exist between viruses and other triggers, increasing the
      likelihood of an exacerbation. In this article we begin with an overview of the
      health, economic, and social burden that exacerbations of asthma carry with them.
      This is followed by a review of the pathogenesis of asthma exacerbations,
      highlighting the various triggers responsible and multiple interactions that
      exist between them. The final section first addresses what preventative measures
      are currently available for asthma exacerbations and subsequently examines which
      of the new treatments in development might lessen the burden of exacerbations in
      the future.

PMID- 22133319
TI  - Plasticity of airway epithelial cells.

PMID- 22133320
TI  - Drug-induced epidermal necrolysis: Important new piece to end the puzzle.

PMID- 22133321
TI  - Asthma and pregnancy.

PMID- 22133323
TI  - Herbal medicines for the management of opioid addiction: safe and effective
      alternatives to conventional pharmacotherapy?
AB  - Striking increases in the abuse of opioids have expanded the need for
      pharmacotherapeutic interventions. The obstacles that confront effective
      treatment of opioid addiction - shortage of treatment professionals, stigma
      associated with treatment and the ability to maintain abstinence - have led to
      increased interest in alternative treatment strategies among both treatment
      providers and patients alike. Herbal products for opioid addiction and
      withdrawal, such as kratom and specific Chinese herbal medications such as
      WeiniCom, can complement existing treatments. Unfortunately, herbal treatments,
      while offering some advantages over existing evidence-based pharmacotherapies,
      have poorly described pharmacokinetics, a lack of supportive data derived from
      well controlled clinical trials, and severe toxicity, the cause for which remains
      poorly defined. Herbal products, therefore, require greater additional testing in
      rigorous clinical trials before they can expect widespread acceptance in the
      management of opioid addiction.

PMID- 22133324
TI  - Pharmacological management of acute and persistent aggression in forensic
      psychiatry settings.
AB  - Aggressive behaviour is common in forensic psychiatric settings. The aetiology of
      aggressive behaviour is multifactorial and can be driven by psychosis,
      impulsivity, psychopathy, intoxication, cognitive impairment, or a combination of
      all of these. Recognition of the different factors behind the aggression can
      inform medication selection and the relative need for specific environmental and
      behavioural interventions in a forensic psychiatric setting. Acute agitation
      needs to be managed quickly and effectively before further escalation of the
      behavioural dyscontrol occurs. Benzodiazepines and/or antipsychotic medications
      are often used and can be given intramuscularly to achieve a rapid onset of
      action. Available are intramuscular preparations of second-generation
      antipsychotics that have similar efficacy to lorazepam and haloperidol in
      reducing agitation, but are well tolerated and not associated with the
      extrapyramidal adverse effects, including akathisia, that can plague the older
      first-generation antipsychotics. The longer-term management of persistent
      aggressive behaviour can be quite complex. A major obstacle is that the causality
      of aggressive events can differ from patient to patient, and also from event to
      event in the same patient. For patients with schizophrenia and persistent
      aggressive behaviour, clozapine is recommended both for its superior
      antipsychotic effect and its specific anti-hostility effect. Mood stabilizers
      such as valproate may be helpful in instances of poor impulsivity and personality
      disorders. Other agents that have been successfully used include beta
      adrenoceptor antagonists (beta-blockers) and antidepressants.

PMID- 22133325
TI  - Combination therapy for neuropathic pain: a review of current evidence.
AB  - Neuropathic pain is a debilitating chronic condition that remains very difficult
      to treat. Recently, a number of clinical studies have compared the effectiveness
      of combination drug therapy with monotherapy for neuropathic pain treatment. In
      this article, we summarize up-to-date clinical studies of combination therapy for
      the treatment of both cancer- and non-cancer-related neuropathic pain. Despite a
      relatively small number of clinical studies on this topic, several positive
      indications have emerged. First, clinical studies using gabapentin (five positive
      trials) and pregabalin (five positive trials and one negative trial) in
      combination with an opioid, cyclo-oxygenase-2 inhibitor or antidepressant have
      shown positive responses greater than the respective monotherapies for pain
      related to diabetic neuropathy and postherpetic neuropathy. Second, high
      concentration (8%) topical capsaicin and a 5% lidocaine patch seem to be
      effective add-on therapies (a modality of combination therapy) for various
      neuropathic pain conditions. Third, combination therapy for cancer-related
      neuropathic pain has yielded only limited success based on a number of small
      scale clinical studies. While there are benefits of using combination therapy for
      neuropathic pain treatment, including better pain relief and reduced adverse
      effects, more clinical studies are required in order to (i) make head-to-head
      comparisons between combination and single-drug therapies, (ii) identify symptom
      specific combination therapies for distinctive clinical neuropathic pain
      conditions, (iii) explore combination therapies that include non-drug modalities
      such as physical therapy, psychological coping and biofeedback to facilitate
      functional restoration and (iv) develop new and objective evaluation tools for
      clinical outcome assessment.

PMID- 22133328
TI  - Tetrabenazine: for chorea associated with Huntington's disease.
AB  - Oral tetrabenazine is currently the only drug approved by the US FDA for the
      treatment of chorea associated with Huntington's disease (HD). Although the
      precise antichorea mechanism of action is unknown, it most likely involves
      reversible depletion of monoamines, particularly dopamine, from presynaptic
      terminals via inhibition of human vesicular monoamine transporter type 2. In a 12
      week, double-blind, placebo-controlled trial conducted in the US in patients with
      HD, oral tetrabenazine (<=100 mg/day; n = 54) was significantly (p = 0.0001) more
      efficacious than placebo (n = 30) at improving adjusted mean Unified HD Rating
      Scale (UHDRS) total maximum chorea scores (reduced from baseline by 5 vs 1.5)
      [primary endpoint]. After 12 weeks, improvements in UHDRS total maximum chorea
      scores of >3 were achieved by significantly (p < 0.0001) more patients in the
      tetrabenazine group than in the placebo group. The antichorea efficacy of
      tetrabenazine was maintained in an 80-week extension study (n = 75), with the
      adjusted mean UHDRS total maximum chorea score significantly (p < 0.001) reduced
      from baseline (score of 14.9) by 4.6 points (primary outcome). In the 12-week
      trial and 80-week extension study, treatment-emergent adverse events in the
      tetrabenazine group mainly occurred during the dosage-titration phase, a period
      during which the dosage was individually optimized. Most of these events were
      mild to moderate and were manageable with dosage adjustments or discontinuation
      of study drug.

PMID- 22133329
TI  - Texting and accessing the web while driving: traffic citations and crashes among
      young adult drivers.
AB  - OBJECTIVE: We examined relations between young adult texting and accessing the
      web while driving with driving outcomes (viz. crashes and traffic citations). Our
      premise is that engaging in texting and accessing the web while driving is not
      only distracting but that these activities represent a pattern of behavior that
      leads to an increase in unwanted outcomes, such as crashes and citations.
      METHODS: College students (N = 274) on 3 campuses (one in California and 2 in
      Utah) completed an electronic questionnaire regarding their driving experience
      and cell phone use. RESULTS: Our data indicate that 3 out of 4 (74.3%) young
      adults engage in texting while driving, over half on a weekly basis (51.8%), and
      some engage in accessing the web while driving (16.8%). Data analysis revealed a
      relationship between these cell phone behaviors and traffic citations and
      crashes. CONCLUSION: The findings support Jessor and Jessor's (1977) "problem
      behavior syndrome" by showing that traffic citations are related to texting and
      accessing the web while driving and that crashes are related to accessing the web
      while driving. Limitations and recommendations are discussed.

PMID- 22133327
TI  - Monoamine oxidase B inhibitors for the treatment of Parkinson's disease: a review
      of symptomatic and potential disease-modifying effects.
AB  - Parkinson's disease is a disorder characterized pathologically by progressive
      neurodegeneration of the dopaminergic cells of the nigrostriatal pathway.
      Although the resulting dopamine deficiency is the cause of the typical motor
      features of Parkinson's disease (bradykinesia, rigidity, tremor), additional non
      motor symptoms appear at various timepoints and are the result of non-dopamine
      nerve degeneration. Monoamine oxidase B (MAO-B) inhibitors are used in the
      symptomatic treatment of Parkinson's disease as they increase synaptic dopamine
      by blocking its degradation. Two MAO-B inhibitors, selegiline and rasagiline, are
      currently licensed in Europe and North America for the symptomatic improvement of
      early Parkinson's disease and to reduce off-time in patients with more advanced
      Parkinson's disease and motor fluctuations related to levodopa. A third MAO-B
      inhibitor (safinamide), which also combines additional non-dopaminergic
      properties of potential benefit to Parkinson's disease, is currently under
      development in phase III clinical trials as adjuvant therapy to either a dopamine
      agonist or levodopa. MAO-B inhibitors have also been studied extensively for
      possible neuroprotective or disease-modifying actions. There is considerable
      laboratory evidence that MAO-B inhibitors do exert some neuroprotective
      properties, at least in the Parkinson's disease models currently available.
      However, these models have significant limitations and caution is required in
      assuming that such results may easily be extrapolated to clinical trials.
      Rasagiline 1 mg/day has been shown to provide improved motor control in terms of
      Unified Parkinson's Disease Rating Scale (UPDRS) score at 18 months in those
      patients with early disease who began the drug 9 months before a second group.
      There are a number of possible explanations for this effect that may include a
      disease-modifying action; however, the US FDA recently declined an application
      for the licence of rasagiline to be extended to cover disease modification.

PMID- 22133330
TI  - Effects of age and the use of hands-free cellular phones on driving behavior and
      task performance.
AB  - OBJECTIVE: This study used a driving simulator to investigate the effect of using
      a Bluetooth hands-free cellular phone earpiece on the driving behavior of two age
      groups. METHODS: Forty-eight participants (24 aged 20-26 and 24 aged 65-73) were
      examined to assess their performance on the following divided-attention tasks
      under 2 driving load conditions (high and low): (1) attempting to maintain the
      speed limit and (2) using a cellular phone while driving. The length of the call
      conversation (long vs. short) and the conversational content (complex vs. simple)
      were manipulated as within-subject independent variables. The driving behavior of
      the participants, their task reaction times and accuracy, and subjective ratings
      were collected as dependent variables. RESULTS: The results indicate that under
      low driving loads, short talk times, and simple conversational content, the
      driving behavior of the participants showed low variance in the vehicle's mean
      speed. In contrast, complex conversation had a significantly negative impact on
      driving behavior. Notably, under a low driving load, motorists' driving
      behaviors, measured in lateral acceleration, caused significantly smaller
      variance in complex conversations compared to no call and simple conversations.
      The use of a hands-free cellular phone affected the performance (acceleration,
      lane deviation, reaction time, and accuracy) of older drivers significantly more
      than younger drivers. While performing divided attention tasks, the accuracy of
      the older drivers was 66.3 percent and that of the younger drivers was 96.3
      percent. Although this study did not find a clear impact of cellular phone use on
      the driving behavior of younger drivers, their divided-attention task reaction
      times and accuracy were better under no-call than calling conditions.
      CONCLUSIONS: This study indicates that the use of hands-free cellular phones
      could significantly affect the safety of driving among the older and present
      risks, although lesser, for younger drivers.

PMID- 22133326
TI  - Atypical antipsychotic-induced weight gain: insights into mechanisms of action.
AB  - Prescriptions for second-generation antipsychotics (SGAs) have surpassed those
      for first-generation agents in the treatment of schizophrenia and bipolar
      disorder. While SGAs have the benefit of a much reduced risk of causing movement
      disorders, they have been associated with weight gain and metabolic effects.
      These adverse reactions are not uncommon, and threaten to have a significant
      impact on the patient's health over the long-term treatment that the patient
      requires. Currently, the aetiology of these effects is not known. This article
      reviews the data exploring the weight gain phenomenon. The literature was
      reviewed from searches of PubMed and the references of major articles in the
      field. The SGAs present a heterogeneous risk for weight gain. In addition,
      different individuals receiving the same drug can exhibit substantially different
      weight changes. This pattern suggests that a group of factors are associated with
      the weight gain phenomenon rather than a single mechanism. Coupled with the
      genetic profile that the patient brings to the treatment, the risk for SGA
      induced weight gain will be different for different drugs and different
      individuals. Targets for exploration of the weight gain phenomenon include
      receptor interactions involving serotonin, histamine, dopamine, adrenergic,
      cannabinoid and muscarinic receptors. The association of SGA-induced weight gain
      and the role of orexigenic and anorexigenic peptides are reviewed. Also, a brief
      discussion of genetic factors associated with SGA-induced weight gain is
      presented, including that of the serotonin 5-HT(2C) receptor gene (HTR2C) and the
      cannabinoid 1 receptor gene (CNR1). The most promising data associated with SGA
      induced weight gain include investigations of the histamine H(1), 5-HT(2A), 5
      HT(2C), muscarinic M(3) and adrenergic receptors. In addition, work in the
      genetic area promises to result in a better understanding of the variation in
      risk associated with different individuals.

PMID- 22133331
TI  - Mileage, car ownership, experience of punishment avoidance, and the risky driving
      of young drivers.
AB  - OBJECTIVE: Young drivers are at greatest risk of injury or death from a car crash
      in the first 6 months of independent driving. In Queensland, the graduated driver
      licensing (GDL) program was extensively modified in July 2007 in order to reduce
      this risk. Increased mileage and car ownership have been found to play a role in
      risky driving, offenses, and crashes; however, GDL programs typically do not
      consider these variables. In addition, young novice drivers' experiences of
      punishment avoidance have not previously been examined. This article explores the
      mileage (duration and distance), car ownership, and punishment avoidance
      behaviors of young newly licensed intermediate (provisional) drivers and their
      relationship to risky driving, crashes, and offenses. METHODS: Drivers (n = 1032)
      aged 17 to 19 years recruited from across Queensland for longitudinal research
      completed survey 1 exploring prelicense and learner experiences and
      sociodemographic characteristics. survey 2 explored the same variables with a
      subset of these drivers (n = 341) after they had completed their first 6 months
      of independent driving. RESULTS: Most young drivers in survey 2 reported owning a
      vehicle and paying attention to police presence. Drivers who had their own cars
      reported significantly greater mileage and more risky driving. Novices who drove
      more kilometers, spent more hours each week driving, or avoided actual and
      anticipated police presence were more likely to report risky driving. These
      drivers were also more likely to report being detected by police for a driving
      related offense. The media, parents, friends, and other drivers play a pivotal
      role in informing novices of on-road police enforcement operations. CONCLUSIONS:
      GDL programs should incorporate education for the parent and novice driver
      regarding the increased risks associated with greater driving, particularly when
      the novice driver owns a vehicle. Parents should be encouraged to delay exclusive
      access to a vehicle. Parents should also consider whether their young novices
      will deliberately avoid police if they are aware of their location. This may
      reinforce not only the risky behavior but also young novices' beliefs that their
      parents condone this behavior.

PMID- 22133332
TI  - Changes in self-regulatory driving among older drivers over time.
AB  - OBJECTIVES: The primary goal of the study was to identify to what extent older
      people modify their driving, what influences them to do so, and how self
      regulatory behavior changes over time in relation to changes in perceived
      impairments and lifestyle characteristics. METHODS: Participants 65 and older (n
      = 2650) were recruited while renewing their driver's licenses in Connecticut,
      Kentucky, and Rhode Island and were interviewed by telephone about current
      driving patterns, recent changes in driving, functional abilities related to
      driving (i.e., vision, memory, physical mobility, diagnosed medical conditions),
      crash involvements, and lifestyle characteristics. Participants were called
      annually to participate in follow-up telephone interviews; 2057 completed a
      second interview, 1698 completed 3 interviews, and 1437 completed all 4
      interviews. Stepwise regression analyses examined how changes in impairments and
      life events (i.e., retiring, becoming widowed or divorced) related to changes in
      the number of miles driven during a typical week and in the number of driving
      situations avoided. RESULTS: Based on information provided in the initial survey,
      participants who completed all 4 surveys were slightly younger, more likely to be
      married, slightly less impaired in terms of physical mobility and medical
      conditions, and drove more weekly miles and avoided fewer driving situations
      compared with those who dropped out. Participants who completed all 4 interviews
      reported driving an average of 94 miles per week in year 1 compared with 78 miles
      in year 4. Reported impairments generally were low to moderate and changed
      little. Analyses comparing years 1 and 4 indicated that drivers drove 35 fewer
      miles per week if they retired or lost their job and 61 fewer miles if they moved
      from a retirement home to a private home or assisted living. They drove 25 more
      miles per week on average if they became widowed or divorced. Small increases in
      the number of driving situations avoided were associated with increasing
      impairments in memory and mobility. CONCLUSIONS: Lifestyle changes such as
      becoming widowed or divorced or retiring were associated with changes in
      mileages. Older drivers with worsening memory and physical mobility regulated
      their driving to some extent by avoiding more driving situations, confirming the
      hypothesis that some older drivers do take steps to compensate for increases in
      some perceived impairments. However, during the 3-year study period, reported
      changes were not large, perhaps because older drivers with larger changes were
      among those who dropped out (46% of those who took the first survey).

PMID- 22133333
TI  - Fluctuating attentional demand in a simulated driving assessment: the roles of
      age and driving complexity.
AB  - OBJECTIVE: The purpose of the study was to explore age differences in attentional
      demand in response to driving situations of varying complexity within the context
      of a simulated assessment protocol. It was hypothesized that as road complexity
      increased, an indicator of attentional demand (i.e., latency to respond to a
      secondary task) would increase and, independent of the road complexity, older
      adults would exhibit greater attentional demand in comparison with younger and
      middle-aged drivers. METHODS: Drivers from 3 age categories (i.e., young, middle
      aged, and older) completed an assessment protocol in a STISIM driving simulator
      (Systems Technology, Inc., Hawthorne, CA) during which participants responded to
      a series of strategically placed secondary tasks (i.e., peripheral detection
      tasks, PDTs). Situations where secondary tasks occurred were grouped according to
      whether they were straight-road, crossing-path, or lane-change events. Two global
      indices of driving safety as well as several cognitive measures external to the
      driving simulator were also collected. RESULTS: The results supported the
      hypothesis in that complex driving situations elicited greater attentional demand
      among drivers of all ages. Older adults showed greater attentional demand in
      comparison to young and middle-aged adults even after controlling for baseline
      response time. Older drivers also scored poorer on a global measure of driving
      safety. CONCLUSIONS: The findings are highly consistent with the literature on
      road complexity and attention that show that increased driving complexity is
      associated with poorer performance on tasks designed to concurrently assess
      attention, an effect that is more pronounced for older drivers. The results point
      to intrinsic and extrinsic factors that contribute to motor vehicle collisions
      (MVCs) among older drivers. The relevance of these findings is discussed in
      relation to interventions and future research aimed at improving road safety.

PMID- 22133334
TI  - Recent changes in the age composition of U.S. drivers: implications for the
      extent, safety, and environmental consequences of personal transportation.
AB  - OBJECTIVE: This study examined the changes in the United States from 1983 to 2008
      in the percentage of persons with driver's licenses as a function of age. METHOD:
      The analysis used data from the Federal Highway Administration on driver's
      licenses by age. RESULTS: (1) Over the past 25 years, there was a substantial
      decrease in the percentage of young people with a driver's license and a
      substantial increase in the percentage of older people with a driver's license.
      (2) For cohorts who were between age 20 and 44 in 1983 (and thus between age 45
      and 69 in 2008), the percentage of licensed drivers has not changed appreciably
      between 1983 and 2008. This finding suggests that, for all practical purposes,
      all those who wanted to obtain a driver's license did so by age 20. (3) For
      cohorts who were between age 45 and 59 in 1983 (and thus between age 70 and 84 in
      2008), this percentage dropped substantially. This finding reflects the
      surrendering of driver's licenses with advanced age. CONCLUSION: The age
      composition of US drivers has changed substantially between 1983 and 2008. In
      1983, the largest group of drivers included those between 25 and 29 years of age.
      In contrast, in 2008, the largest group included those 70 years and older.

PMID- 22133335
TI  - Diurnal variation and injury due to motor vehicle crashes in older trauma
      patients.
AB  - OBJECTIVE: By 2030 it is expected the elderly will comprise 25 percent of the
      drivers in the United States. It is also estimated that currently in the United
      States alone, 500 older adults are injured each day in motor vehicle crashes
      (MVCs). Current research has not been able to consistently produce a direct
      connection between MVCs and specific age-related changes. It is speculated that
      crash rates are more likely linked to an interaction between driver
      characteristics and driving conditions as well as the driving environment.
      Sundowner's syndrome occurs in older drivers starting in the late afternoon
      through early evening (generally between 3:00 pm and 8:00 pm) and involves
      behaviors such as confusion, disorientation, and restlessness. The following
      retrospective study was designed to assess the frequency of older drivers
      admitted to a trauma service due to an MVC based on the time of day of the MVC
      compared to younger and middle-aged drivers. METHODS: The study included all
      adult trauma patients >= 21 years of age admitted to a Level 1 trauma center due
      to a, MVC, in which they were the driver of the vehicle, between January 1, 2005,
      and December 31, 2010. RESULTS: A 3 (Injury Time Period) * 7 (Age Category) chi
      square was performed to assess whether there was a disproportionate number of
      patients admitted as a function of time of injury and age. The overall chi-square
      was statistically significant. Consequently, a 3 * 7 analysis of variance (ANOVA)
      was performed on injury severity score (ISS). Tukey's posttest revealed that ISS
      was highest during the early evening time period. CONCLUSIONS: The evidence of
      the early evening time period having a differential impact on older drivers is
      through a demonstration of an Injury Time Period * Age Category interaction. This
      interaction was found to substantiate the hypothesis that older drivers have a
      disproportionately higher rate of injury due to an MVC during the early evening
      time period than younger and middle-aged drivers. In identifying the early
      evening's time period as a time in which older drivers are more likely to
      experience injury from an MVC than younger and middle-aged drivers, we believe
      that our research adds insight into why age restrictions have not been successful
      in reducing crash rates in the older driver population. It is the compound effect
      of age-related changes and environmental conditions that contributes to the
      higher proportion of MVCs. Age restrictions alone do not take into account
      environmental conditions.

PMID- 22133336
TI  - Driving while black: a comparison of the beliefs, concerns, and behaviors of
      black and white Maryland drivers.
AB  - OBJECTIVE: The National Highway Traffic Safety Administration suggests that given
      the changing demographics of the United States it is important to examine motor
      vehicle statistics by race and ethnicity. The current study sought to explore
      differences in traffic safety concerns and driving behaviors between black and
      white drivers. METHODS: An annual, anonymous, random-digit-dial telephone survey
      was used to collect data between 2003 and 2009 from Maryland drivers. Drivers (N
      = 5503) were assessed regarding their driving behaviors and perceived risk of
      receiving a traffic violation. RESULTS: Results showed that black drivers
      perceived a greater likelihood of being stopped for driving under the influence
      (DUI), for not wearing a seat belt and for speeding than white drivers. These
      differences were found among drivers with or without a history of being ticketed.
      Black drivers were also more likely to report a variety of risky driving
      behaviors than white drivers. However, black drivers were not more likely to
      report receiving a ticket or citation in the last month after controlling for
      demographic factors, risky driving behaviors, and geographic region of the state,
      where traffic enforcement may vary. CONCLUSIONS: Findings indicate that black
      drivers are not more likely to be ticketed, despite perceptual biases that may
      exist among some drivers. These differences appear to be explained by demographic
      as well as regional factors. These results highlight the need for more research
      to understand the potential differences in driving behaviors between racial and
      ethnic groups. More research is also needed to develop countermeasures for racial
      and ethnic groups most at risk for motor vehicle violations and crashes.

PMID- 22133337
TI  - The correlation between pedestrian injury severity in real-life crashes and Euro
      NCAP pedestrian test results.
AB  - OBJECTIVE: The aim of the present study was to estimate the correlation between
      Euro NCAP pedestrian rating scores and injury outcome in real-life car-to
      pedestrian crashes, with special focus on long-term disability. Another aim was
      to determine whether brake assist (BA) systems affect the injury outcome in real
      life car-to-pedestrian crashes and to estimate the combined effects in injury
      reduction of a high Euro NCAP ranking score and BA. METHODS: In the current
      study, the Euro NCAP pedestrian scoring was compared with the real-life outcome
      in pedestrian crashes that occurred in Sweden during 2003 to 2010. The real-life
      crash data were obtained from the data acquisition system Swedish Traffic
      Accident Data Acquisition (STRADA), which combines police records and hospital
      admission data. The medical data consisted of International Classification of
      Diseases (ICD) diagnoses and Abbreviated Injury Scale (AIS) scoring. In all,
      approximately 500 pedestrians submitted to hospital were included in the study.
      Each car model was coded according to Euro NCAP pedestrian scores. In addition,
      the presence or absence of BA was coded for each car involved. Cars were grouped
      according to their scoring. Injury outcomes were analyzed with AIS and, at the
      victim level, with permanent medical impairment. This was done by translating the
      injury scores for each individual to the risk of serious consequences (RSC) at 1,
      5, and 10 percent risk of disability level. This indicates the total risk of a
      medical disability for each victim, given the severity and location of injuries.
      The mean RSC (mRSC) was then calculated for each car group and t-tests were
      conducted to falsify the null hypothesis at p <= .05 that the mRSC within the
      groups was equal. RESULTS: The results showed a significant reduction of injury
      severity for cars with better pedestrian scoring, although cars with a high score
      could not be studied due to lack of cases. The reduction in RSC for medium
      performing cars in comparison with low-performing cars was 17, 26, and 38 percent
      for 1, 5, and 10 percent of medical impairment, respectively. These results
      applied to urban areas with speed limits up to 50 km/h, although no significant
      reduction was found in higher speed zones. Regarding cars with BA, the null
      hypothesis could not be rejected at p = .05; hence, no significant results of
      injury reduction were found. CONCLUSIONS: A significant correlation between Euro
      NCAP pedestrian score and injury outcome in real-life car-to-pedestrian crashes
      was found. Injury reduction was found to be higher with increasing severity and
      level of permanent medical impairment. The difference between 1- and 2-star cars
      is 17 percent in mean risk of permanent medical impairment (mRSC) 1%+, 26 percent
      in mRSC 5%+, and 38 percent in mRSC 10%+ for crashes in speed zones up to 50
      km/h. Brake assist was not found to provide a statistically significant injury
      reduction.

PMID- 22133338
TI  - Road traffic injuries in the People's Republic of China, 1951-2008.
AB  - OBJECTIVE: Road traffic injuries (RTIs) have become the leading cause of injury
      deaths in China. This article analyzed the trends in all crashes, nonfatal
      injuries, and fatalities from road traffic crashes from 1951 to 2008 and compared
      the crash frequency, crash severity, and crash patterns by provinces, types of
      road, and injured road users. METHODS: Road traffic crash data were obtained from
      the Bureau of Traffic Management at the Ministry of Public Security and National
      Bureau of Statistics of China. Descriptive statistical analyses were conducted.
      RESULTS: Over the past 5 decades, road traffic injuries have increased
      substantially in China. From 1951 to 2008, the total number of road traffic
      crashes, nonfatal injuries, and fatalities increased by 43-fold, 58-fold, and 85
      fold, respectively. Linear regression suggested a significant decline of 30.1
      percent (95% confidence interval [CI]: 24.8-35.3) in the mortality rate per
      100,000 people during the period 2002 to 2008. From 2004 to 2008, road traffic
      crash mortality rate per 100,000 people varied greatly in China from the lowest
      of 3.0 in Henan in 2008 to the highest of 21.7 in Xizang in 2004. RTIs in China
      disproportionally affected the following populations: males, persons 21 to 50
      years of age, pedestrians, and motorcyclists/bicyclists. Adults aged more than 65
      years accounted for approximately 10 percent of total road traffic deaths. Road
      types and RTIs severity were closely related; highways were associated with
      greater mortality rates. CONCLUSION: Road traffic injuries have become a
      burgeoning public health problem in China. Programs need to be developed to
      prevent nonfatal injuries and fatalities caused by road traffic crashes in this
      emerging country.

PMID- 22133339
TI  - Evaluation of insight training of ambulance drivers in Sweden using DART, a new e
      learning tool.
AB  - OBJECTIVE: The aim of the study was to evaluate whether a new e-learning tool for
      insight training of ambulance drivers can have an effect on drivers' driving
      behaviors, perceived driving competence, competence to assess risks, self
      reflection, and safety attitudes. METHODS: A quasi-experimental study design,
      with participants nonrandomly assigned into a control and intervention group, was
      used. The intervention group participated in the insight-training course and the
      control group did not. Both groups completed a self- and peer assessment online
      questionnaire before and after the training. RESULTS: The main finding is that
      the ambulance drivers assessed themselves through the instruments after the
      training, with the e-learning tool Driver Access Recording Tool (DART), as safer
      drivers in the areas of speed adaptation, closing up, and overtaking. In the
      answers from the group-based evaluation, the ambulance drivers responded that
      they were more reflective/analytical, had increased their risk awareness, and had
      changed their driving behaviors. CONCLUSIONS: After insight training, the
      ambulance drivers in this study assessed themselves as safer drivers in several
      important areas, including speed adaptation, closing up, and overtaking. In
      future training of ambulance drivers there should be more focus on insight
      training instead of previous training focusing on maneuvering capabilities.

PMID- 22133340
TI  - Effect of directional speech warnings on road hazard detection.
AB  - BACKGROUND: In the last 2 decades, cognitive science and the transportation
      psychology field have dedicated a lot of effort to designing advanced driver
      support systems. Verbal warning systems are increasingly being implemented in
      modern automobiles in an effort to increase road safety. OBJECTIVE: The study
      presented here investigated the impact of directional speech alert messages on
      the participants' speed to judge whether or not naturalistic road scenes depicted
      a situation of impending danger. METHOD: Thirty-eight volunteers performed a
      computer-based key-press reaction time task. RESULTS: Findings indicated that
      semantic content of verbal warning signals can be used for increasing driving
      safety and improving hazard detection. Furthermore, the classical result
      regarding signal accuracy is confirmed: directional informative speech messages
      lead to faster hazard detection compared to drivers who received a high rate of
      false alarms. CONCLUSION: Notwithstanding some study limitations (lack of driver
      experience and low ecological validity), this evidence could provide important
      information for the specification of future Human-Machine-interaction (HMI)
      design guidelines.

PMID- 22133341
TI  - Identifying significant predictors of head-on conflicts on two-lane rural roads
      using inductive loop detectors data.
AB  - OBJECTIVE: To identify the significant factors that influence head-on conflicts
      resulting from dangerous overtaking maneuvers on 2-lane rural roads in Iran.
      METHODS: A traffic conflict technique was applied to 12 two-lane rural roads in
      order to investigate the potential situations for accidents to occur and thus to
      identify the geometric and traffic factors affecting traffic conflicts. Traffic
      data were collected via the inductive loop detectors installed on these roads,
      and geometric characteristics were obtained through field observations. Two
      groups of data were then analyzed independently by Pearson's chi-square test to
      evaluate their relationship to traffic conflicts. The independent variables were
      percentage of time spent following (PTSF), percentage of heavy vehicles,
      directional distribution of traffic (DDT), mean speed, speed standard deviation,
      section type, road width, longitudinal slope, holiday or workday, and lighting
      condition. RESULTS: It was indicated that increasing the PTSF, decreasing the
      percentage of heavy vehicles, increasing the mean speed (up to 75 km/h),
      increasing DDT in the range of 0 to 60 percent, and decreasing the standard
      deviation of speed significantly increased the occurrence of traffic conflicts.
      It was also revealed that traffic conflicts occur more frequently on curve
      sections and on workdays. The variables road width, slope, and lighting condition
      were found to have a minor effect on conflict occurrence. CONCLUSION: To reduce
      the number of head-on conflicts on the aforementioned roads, some remedial
      measures are suggested, such as not constructing long "No Passing" zones and
      constructing passing lanes where necessary; keeping road width at the standard
      value; constructing roads with horizontal curves and a high radius and using
      appropriate road markings and overtaking-forbidden signs where it is impossible
      to modify the radius; providing enough light and installing caution signs/devices
      on the roads; and intensifying police control and supervision on workdays,
      especially in peak hours.

PMID- 22133346
TI  - FDG PET/CT appearance of multicentric Castleman's disease mimicking lymphoma.
AB  - We report a case of a multicentric form of Castleman's disease with multiple
      lymph nodes showing intense FDG uptake on whole body scan mimicking non-Hodgkin's
      lymphoma. In this report, the patient had multiple cervical, mediastinal, hilar,
      retroperitoneal and abnormal lymph nodes in the groin. (18)F-fluorodeoxyglucose
      positron emission tomography/computed tomography was performed before tissue
      sampling. (18)F-FDG/PET demonstrated multiple areas of increased uptake in
      cervical, mediastinal, hilar, retroperitoneal and groin lymph nodes, suggesting a
      generalized disease of the lymphatic system including non-Hodgkin's lymphoma. The
      final diagnosis is based on the histopathological findings of the material
      obtained from the cervical lymphadenectomy. The histological diagnosis was
      multicentric plasma cell variant of Castleman's disease. (18)F fluorodeoxyglucose
      positron emission tomography/computed tomography scan helped to identify the
      lymph nodes involved throughout the whole body, but did not help to differentiate
      non-Hodgkin's lymphoma. The clinical conclusions and PET/CT findings are
      described in this report.

PMID- 22133343
TI  - Cytokines and the regulation of fungus-specific CD4 T cell differentiation.
AB  - CD4 T cells play important and non-redundant roles in protection against
      infection with diverse fungi. Distinct CD4 T cell subsets can mediate protection
      against fungal disease where Th1 and Th17 CD4 T cell subsets have been found to
      promote fungal clearance and protective immunity against diverse fungal
      pathogens. The differentiation of naive CD4 T cells into Th1 or Th17 cells is
      crucially controlled by their interaction with dendritic cells and instructed by
      cytokines. IL-12 and IFN-gamma promote Th1 differentiation while TGF-beta, IL-6,
      IL-1, IL-21 and IL-23 promote Th17 differentiation and maintenance. The
      production of these cytokines by DCs is in turn regulated by innate receptors
      triggered in response to fungal infection. In this review we will discuss the
      contributions of cytokines found to influence fungus-specific CD4 T cell
      differentiation and their role in defense against fungal disease. We will also
      highlight the contributions of innate receptors involved in recognition of fungi
      and how they shape cytokine secretion and CD4 T cell differentiation.

PMID- 22133344
TI  - Relationships among the concentrations of 25 inflammation-associated proteins
      during the first postnatal weeks in the blood of infants born before the 28th
      week of gestation.
AB  - BACKGROUND: Inflammation appears to be involved in processes leading to organ
      damage in preterm newborns, yet little is known about the relationships among
      elevated concentrations of inflammation-associated proteins in the blood of
      preterm newborns. METHODS: In this exploratory study, we used an
      electrochemiluminescence method to measure 25 proteins in blood obtained on
      postnatal day 1 (range 1-3), day 7 (range 5-8), and day 14 (range 12-15) from 939
      children born before the 28th week of gestation and evaluated to what extent
      those whose concentration of each protein was elevated (defined as in the highest
      quartile for gestational age and day the specimen was obtained) also had an
      elevated concentration of every other protein the same day or on a day 1 or 2
      weeks later (p<.0001). RESULTS: On each of the 3 days assessed, elevated
      concentrations of 17 proteins were associated with elevated concentrations of 15
      or more of the other 24 proteins. VEGF, VEGF-R1, VEGF-R2 were among these
      proteins, while IGFBP-1 was associated with 13 other proteins on day 7. An
      elevated concentration of eight proteins on day 1 predicted an elevated
      concentration of 10 or more proteins on day 7, while an elevated concentration of
      only two proteins on day 7 were associated with elevated concentrations of 10 or
      more proteins on day-14. Few associations were seen between days 1 and 14.
      CONCLUSIONS/INFERENCES: Inflammation is a diffuse process in ELGANs, with
      elevated concentrations of cytokines, chemokines, adhesion molecules, matrix
      metalloproteinases, a growth factor and its receptors, as well as a growth factor
      binding protein associated with each other the same day, as well as on subsequent
      days.

PMID- 22133347
TI  - Temporal trend and climate factors of hemorrhagic fever with renal syndrome
      epidemic in Shenyang City, China.
AB  - BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an important
      infectious disease caused by different species of hantaviruses. As a rodent-borne
      disease with a seasonal distribution, external environmental factors including
      climate factors may play a significant role in its transmission. The city of
      Shenyang is one of the most seriously endemic areas for HFRS. Here, we
      characterized the dynamic temporal trend of HFRS, and identified climate-related
      risk factors and their roles in HFRS transmission in Shenyang, China. METHODS:
      The annual and monthly cumulative numbers of HFRS cases from 2004 to 2009 were
      calculated and plotted to show the annual and seasonal fluctuation in Shenyang.
      Cross-correlation and autocorrelation analyses were performed to detect the
      lagged effect of climate factors on HFRS transmission and the autocorrelation of
      monthly HFRS cases. Principal component analysis was constructed by using climate
      data from 2004 to 2009 to extract principal components of climate factors to
      reduce co-linearity. The extracted principal components and autocorrelation terms
      of monthly HFRS cases were added into a multiple regression model called
      principal components regression model (PCR) to quantify the relationship between
      climate factors, autocorrelation terms and transmission of HFRS. The PCR model
      was compared to a general multiple regression model conducted only with climate
      factors as independent variables. RESULTS: A distinctly declining temporal trend
      of annual HFRS incidence was identified. HFRS cases were reported every month,
      and the two peak periods occurred in spring (March to May) and winter (November
      to January), during which, nearly 75% of the HFRS cases were reported. Three
      principal components were extracted with a cumulative contribution rate of
      86.06%. Component 1 represented MinRH0, MT1, RH1, and MWV1; component 2
      represented RH2, MaxT3, and MAP3; and component 3 represented MaxT2, MAP2, and
      MWV2. The PCR model was composed of three principal components and two
      autocorrelation terms. The association between HFRS epidemics and climate factors
      was better explained in the PCR model (F = 446.452, P < 0.001, adjusted R2 =
      0.75) than in the general multiple regression model (F = 223.670, P < 0.000,
      adjusted R2 = 0.51). CONCLUSION: The temporal distribution of HFRS in Shenyang
      varied in different years with a distinctly declining trend. The monthly trends
      of HFRS were significantly associated with local temperature, relative humidity,
      precipitation, air pressure, and wind velocity of the different previous months.
      The model conducted in this study will make HFRS surveillance simpler and the
      control of HFRS more targeted in Shenyang.

PMID- 22133348
TI  - Palladium-catalyzed C3-benzylation of indoles.
AB  - A general method for regioselective C3-benzylation of indoles has been developed.
      Various 3-substituted indoles and benzyl methyl carbonates with different
      electronic properties react under mild conditions to afford a diverse range of 3
      benzylindolenine products in good yields.

PMID- 22133349
TI  - Wound pH-responsive sustained release of therapeutics from a poly(NIPAAm-co-AAc)
      hydrogel.
AB  - Wound pH strongly influences residence time and activity of various growth
      factors during wound healing. Hence, a pH-responsive sustained release growth
      factor delivery system could be beneficial for effective treatment of wound. In
      this context, an effort was made to evaluate the potential  of a poly(N
      isopropylacrylamide-co-acrylic acid) hydrogel as pH-sensitive sustained release
      system for wound-pH-dependent therapeutics delivery. The polymer was synthesized
      via radical copolymerization and influence of pH on lower critical solution
      temperature (LCST), microarchitechture  and swelling of the hydrogel was
      evaluated. Results showed a pH-dependent variation in the physical properties of
      the hydrogel within the wound pH range. Fluorescence recovery after
      photobleaching (FRAP) analysis endorsed a pH dependent restricted diffusion of
      the BSA in the hydrogel. Later,  release of bovine serum albumin (BSA), vascular
      endothelial growth factor (VEGF) and epidermal growth factor (EGF) (each 5%, w/v)
      from the hydrogel within the range of wound pH (pH 6.7-7.9) were examined.
      Analysis showed non-Fickian release of therapeutics from the hydrogel with a
      significant  variation in release rate and cumulative release with the increase
      in pH. Retention of the bioactivity of the released EGF was confirmed by studying
      murine dermal fibroblast cell proliferation in vitro. Finally, a growth factor
      (EGF or VEGF)-loaded hydrogel was applied on a murine excisional  wound model and
      showed augmentation of wound healing in comparison to conventional sustained
      release growth factor therapy.

PMID- 22133350
TI  - Studies on guanidinated N-3-aminopropyl methacrylamide-N-2-hydroxypropyl
      methacrylamide co-polymers as gene delivery carrier.
AB  - Guanidinated N-3-aminopropyl methacrylamide (APMA)-N-2-hydroxypropyl
      methacrylamide (HPMA) co-polymers were prepared and evaluated to develop novel
      non-viral gene transfection carriers. The co-polymers were synthesized via
      radical co-polymerization of APMA and HPMA followed by  total guanidination of
      amino groups, which employed guanidinated APMA (GPMA) for increasing cell
      penetrating and HPMA as the positive shielding content. The molecular weight of
      guanidinated APMA-HPMA co-polymers (GPMA-HPMA) was determined by static light
      scattering. Furthermore,  cytotoxicity and transfection experiments of GPMA
      HPMA/pDNA complexes were conducted. A significant decrease of their parent
      cytotoxicity and an efficient transfection at relative low charge ratios were
      observed. The cellular distribution of most GPMA-HPMA/pDNA complexes was
      partially  localized in the nucleus, as indicated by confocal laser scanning
      microscopy. The guanidination strategy employed may lead to non-viral gene
      delivery carriers that combine satisfactory transfection efficiency and
      cytotoxicity, which contribute to their cell-penetrating ability.

PMID- 22133351
TI  - Substrates for human pluripotent stem cell cultures in conditioned medium of
      mesenchymal stem cells.
AB  - We aimed to establish a culture system of human pluripotent stem cells (hPSCs),
      such as human embryonic stem cells (hESCs) and human induced pluripotent stem
      cells (hiPSCs), free from xenogeneic proteins, Matrigel(TM) and conditioned
      medium of mouse embryonic fibroblasts.  The conditioned culture medium consisted
      of mesenchymal stem cells derived from human bone marrow. We examined surface
      properties suitable for hPSC culture by using self-assembled monolayers (SAMs) of
      alkanethiols with four different functional groups: CH(3), OH, COOH and NH(2). 
      hPSCs neither adhered nor proliferated on surfaces with a water contact angle
      higher than 40 degrees . Based on this finding, the contact angle of a
      polystyrene (PSt) culture dish was reduced to less than 40 degrees , and COOH and
      OH groups were introduced to its surface by oxygen plasma treatment,  making the
      PSt dish suitable for hPSC culture. This combination of a PSt dish treated with
      oxygen plasma treatment and conditioned medium of mesenchymal stem cells achieved
      a long-term maintenance of hPSCs without differentiation.

PMID- 22133352
TI  - Characterization of lead resistant endophytic Bacillus sp. MN3-4 and its
      potential for promoting lead accumulation in metal hyperaccumulator Alnus firma.
AB  - The aim of this study was to isolate and characterize endophytic bacteria from
      the roots of the metal hyperaccumulator plant Alnus firma. A total of 14
      bacterial endophytes were isolated from root samples and assayed for tolerance to
      heavy metals. Isolate MN3-4 exhibited maximum bioremoval of Pb and was
      subsequently identified as Bacillus sp. based on 16S rRNA sequences. The pH and
      initial metal concentration highly influenced the Pb bioremoval rate. The growth
      of isolate MN3-4 was moderately altered in the presence of metals. Scanning
      electron microscopy, energy dispersive spectroscopy, biological-transmission
      electron microscopy, and Fourier transform infrared spectroscopy studies revealed
      that isolate MN3-4 had extracellularly sequestered the Pb molecules with little
      intracellular accumulation. Isolate MN3-4 did not harbor pbrA and pbrT genes.
      Moreover, isolate MN3-4 had the capacity to produce siderophores and indoleacetic
      acid. A root elongation assay demonstrated an increase (46.25%) in the root
      elongation of inoculated Brassica napus seedlings compared to that of the control
      plants. Obtained results pointed out that isolate MN3-4 could potentially reduce
      heavy metal phytotoxicity and increase Pb accumulation in A. firma plants.

PMID- 22133353
TI  - Nanostructured TiO2 photocatalysts for the determination of organic pollutants.
AB  - Owing to the inherent advantages of nanostructured TiO(2) photocatalysts,
      including high photocatalytic activity, strong oxidation power, low cost,
      environmental benignity and excellent stability, TiO(2) photocatalyts have
      recently attracted extensive attention from scientific researchers, technology
      developers and investors for use in sensing applications. The TiO(2) sensors can
      be used for lab-based analyses, on-line and on-site determination of organic
      pollutants in wastewater. This work reviews the application of TiO(2)
      nanomaterials in photocatalytic and photoelectrocatalytic monitoring of
      aggregative organic parameters such as total organic carbon (TOC) and chemical
      oxygen demand (COD), as well as individual organic compounds in aqueous solution.

PMID- 22133354
TI  - Hypoxia-induced adaptation to mitral regurgitation: a role for K ATP channel up
      regulation?

PMID- 22133355
TI  - Increased expression of adenosine triphosphate-sensitive K+ channels in mitral
      dysfunction: mechanically stimulated transcription and hypoxia-induced protein
      stability?
AB  - OBJECTIVES: The aim of this study was to test whether adenosine triphosphate
      sensitive K(+) (KATP) channel expression relates to mechanical and hypoxic stress
      within the left human heart. BACKGROUND: The KATP channels play a vital role in
      preserving the metabolic integrity of the stressed heart. However, the mechanisms
      that govern the expression of their subunits (e.g., potassium inward rectifier
      [Kir] 6.2) in adult pathologies are mostly unknown. METHODS: We collected
      biopsies from the 4 cardiac chambers and 50 clinical parameters from 30 surgical
      patients with severe mitral dysfunction. Proteins and messenger ribonucleic acids
      (mRNAs) of KATP pore subunits and mRNAs of their known transcriptional regulators
      (forkhead box [FOX] F2, FOXO1, FOXO3, and hypoxia inducible factor [HIF]-1alpha)
      were measured respectively by Western blotting, immunohistochemistry, and
      quantitative real-time polymerase chain reaction, and submitted to statistical
      analysis. RESULTS: In all heart chambers, Kir6.2 mRNA correlated with HIF-1alpha
      mRNA. Neither Kir6.1 nor Kir6.2 proteins positively correlated with their
      respective mRNAs. The HIF-1alpha mRNA related in the left ventricle to aortic
      pressure, in the left atrium to left atrial pressure, and in all heart chambers
      to a decreased Kir6.2 protein/mRNA ratio. Interestingly, in the left heart,
      Kir6.2 protein and its immunohistochemical detection in myocytes were maximal at
      low venous PO(2). In the left ventricle, the Kir6.2 protein/mRNA ratio was also
      significantly higher at low venous PO(2), suggesting that tissue hypoxia might
      stabilize the Kir6.2 protein. CONCLUSIONS: Results suggest that post
      transcriptional events determine Kir6.2 protein expression in the left ventricle
      of patients with severe mitral dysfunction and low venous PO(2). Mechanical
      stress mainly affects transcription of HIF-1alpha and Kir6.2. This study implies
      that new therapies could aim at the proteasome for stabilizing the left
      ventricular Kir6.2 protein.

PMID- 22133356
TI  - Pneumocystis jiroveci Pneumonia in an Atypical Host.

PMID- 22133357
TI  - Using induced pluripotent stem cells (iPSC) to model human neuromuscular
      connectivity: promise or reality?
AB  - Motor neuron diseases (MND) such as amyotrophic lateral sclerosis and spinal
      muscular atrophy are devastating, progressive and ultimately fatal diseases for
      which there are no effective treatments. Recent evidence from systematic studies
      of animal models and human patients suggests that the neuromuscular junction
      (NMJ) is an important early target in MND, demonstrating functional and
      structural abnormalities in advance of pathological changes occurring in the
      motor neuron cell body. The ability to study pathological changes occurring at
      the NMJ in humans is therefore likely to be important for furthering our
      understanding of disease pathogenesis, and also for designing and testing new
      therapeutics. However, there are many practical and technical reasons why it is
      not possible to visualise or record from NMJs in pre- and early-symptomatic MND
      patients in vivo. Other approaches are therefore required. The development of
      stem cell technologies has opened up the possibility of creating human NMJs in
      vitro, using pluripotent cells generated from healthy individuals and patients
      with MND. This review covers historical attempts to develop mature and functional
      NMJs in vitro, using co-cultures of muscle and nerve from animals, and discusses
      how recent developments in the generation and specification of human induced
      pluripotent stem cells provides an opportunity to build on these previous
      successes to recapitulate human neuromuscular connectivity in vitro.

PMID- 22133359
TI  - Tuning the postfocused size of colloidal nanocrystals by the reaction rate: from
      theory to application.
AB  - We show that adjusting the reaction rate in a hot injection synthesis is a viable
      strategy to tune the diameter of colloidal nanocrystals at the end of the size
      distribution focusing, i.e., the postfocused diameter. The approach is introduced
      by synthesis simulations, which describe nucleation and growth of colloidal
      nanocrystals from a solute or monomer that is formed in situ out of the injected
      precursors. These simulations indicate that the postfocused diameter is reached
      at almost full yield and that it can be adjusted by the rate of monomer
      formation. We implement this size-tuning strategy using a particular CdSe quantum
      dot synthesis that shows excellent agreement with the model synthesis. After
      demonstrating that the reaction rate depends in first order on the Cd and Se
      precursor concentration, the proposed strategy of size control is explored by
      varying the precursor concentration. This enables the synthesis of colloidal
      nanocrystals with a predefined size at almost full yield and sharp size
      distributions. In addition, we demonstrate that the same tuning strategy applies
      to the synthesis of CdS quantum dots. This result is highly relevant especially
      in the context of reaction upscaling and automation. Moreover, the results
      obtained challenge the traditional interpretation of the hot injection synthesis,
      in particular the link between hot injection, burst nucleation, and sharp size
      distributions.

PMID- 22133358
TI  - miR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down
      regulating WT1 protein level.
AB  - BACKGROUND: miR-15a and miR-16-1(miR-15a/16-1) have been implicated as tumor
      suppressors in chronic lymphocytic leukemia, multiple myeloma, and acute myeloid
      leukemic cells. However the mechanism of inhibiting the proliferation of leukemic
      cells is poorly understood. METHODS: K562 and HL-60 cells were transfected with
      pRS-15/16 or pRS-E, cell growth were measured by CCK-8 assay and direct cell
      count. Meanwhile WT1 protein and mRNA level were measured by Western blotting and
      quantitative real-time PCR. RESULTS: In this study we found that over-expression
      of miR-15a/16-1 significantly inhibited K562 and HL-60 cells proliferation.
      Enforced expression of miR-15a/16-1 in K562 and HL-60 cells significantly reduced
      the protein level of WT1 but not affected the mRNA level. However enforced
      expression of miR-15a/16-1 can not reduce the activity of a luciferase reporter
      carrying the 3'-untranslated region(3'UTR) of WT1. Silencing of WT1 by specific
      siRNA suppressed leukemic cells proliferation resembling that of miR-15a/16-1
      over-expression. Anti-miR-15a/16-1 oligonucleotides (AMO) reversed the expression
      of WT1 in K562 and HL-60 cells. Finally, we found a significant inverse
      correlation between miR-15a or miR-16-1 expression and WT1 protein levels in
      primary acute myeloid leukemia (AML) blasts and normal controls. CONCLUSIONS:
      These data suggest that miR-15a/16-1 may function as a tumor suppressor to
      regulate leukemic cell proliferation potentially by down-regulating the WT1
      oncogene. However WT1 is not directly targeted by miR-15a/16-1 through miRNA-mRNA
      base pairing, therefore more study are required to understand the mechanism by
      which miR-15a/16-1 downregulate WT1.

PMID- 22133361
TI  - Persuasive techniques used in television advertisements to market foods to UK
      children.
AB  - The aim of this study was to quantify the nature and extent of use of persuasive
      marketing techniques in television advertisements (adverts) to promote foods to
      children. Popular UK commercial television channels broadcasting
      children's/family viewing were recorded for 2 days (6 am-10 pm) every month in
      2008 and recordings were screened for adverts. Eighteen thousand eight hundred
      and eighty eight adverts were for food and these were coded for peak/non-peak
      children's viewing time and representation of core (healthy)/non-core
      (unhealthy)/miscellaneous foods. The analysis assessed use of persuasive appeals,
      premium offers, promotional characters (brand equity and licensed characters),
      celebrity endorsers and website promotion in food adverts. Promotional
      characters, celebrity endorsers and premium offers were used more frequently to
      promote non-core than core foods, even on dedicated children's channels. Brand
      equity characters featured on a greater proportion of food adverts than licensed
      characters. A food brand website was promoted in a third of food adverts
      (websites are not covered by the statutory regulation on food advertising). This
      extensive analysis of television adverts demonstrated that the use of persuasive
      marketing techniques to promote unhealthy foods was extensive in broadcasting
      popular with children despite regulations. Further studies should incorporate an
      analysis of the content of websites promoted during food adverts.

PMID- 22133362
TI  - Purification and characterization of a novel chitinase gene from Paecilomyces
      thermophila expressed in Escherichia coli.
AB  - A novel chitinase gene (PtChiA) from the thermophilic fungus Paecilomyces
      thermophila was cloned and expressed in Escherichia coli as an intracellular
      soluble protein. The gene sequence alignment indicates that PtChiA belongs to
      glycoside hydrolase (GH) family 18 and has an open reading frame comprising of
      1473 bp nucleotide sequences with five introns. PtChiA encodes 400 amino acids
      without any predicted signal peptide. PtChiA was purified by Ni-IDA
      chromatography. It displayed an acidic optimum pH of 4.5 and broad pH stability
      (pH 4.0-10.5). The enzyme exhibited an optimal temperature of 50 degrees C and
      was stable up to 40 degrees C. PtChiA was strongly inhibited by anionic detergent
      SDS, and also by metal ions Hg(2+) and Mn(2+). It did not exhibit any antifungal
      activity against pathogenic fungi. It has the ability to hydrolyze colloidal
      chitin into chito-oligomers suggesting its use in conversion of chitin waste into
      chito-oligosaccharides.

PMID- 22133363
TI  - Introduction to periodontal epidemiology.

PMID- 22133364
TI  - Global periodontal disease epidemiology.

PMID- 22133365
TI  - Causal theory and the etiology of periodontal diseases.

PMID- 22133366
TI  - Genetic susceptibility to periodontitis.

PMID- 22133368
TI  - Active and passive smoking: assessment issues in periodontal research.

PMID- 22133367
TI  - Socioeconomic position indicators and periodontitis: examining the evidence.

PMID- 22133369
TI  - Nutrition, dietary guidelines and optimal periodontal health.

PMID- 22133370
TI  - Analytic epidemiology and periodontal diseases.

PMID- 22133371
TI  - Regression models in periodontal epidemiology: purpose, approach and
      interpretation.

PMID- 22133372
TI  - Development of prognostic indicators using classification and regression trees
      for survival.

PMID- 22133373
TI  - Using administrative data for epidemiological research: case study to identify
      persons with periodontitis.

PMID- 22133374
TI  - Historical perspectives on theories of periodontal disease etiology.

PMID- 22133375
TI  - Guanylyl cyclase (GC)-A and GC-B activities in ventricles and cardiomyocytes from
      failed and non-failed human hearts: GC-A is inactive in the failed cardiomyocyte.
AB  - Cardiomyocytes release atrial natriuretic peptide (ANP) and B-type natriuretic
      peptide to stimulate processes that compensate for the failing heart by
      activating guanylyl cyclase (GC)-A. C-type natriuretic peptide is also elevated
      in the failing heart and inhibits cardiac remodeling by activating the homologous
      receptor, GC-B. We previously reported that GC-A is the most active membrane GC
      in normal mouse ventricles while GC-B is the most active membrane GC in failing
      ventricles due to increased GC-B and decreased GC-A activities. Here, we examined
      ANP and CNP-specific GC activity in membranes obtained from non-failing and
      failing human left ventricles and in membranes from matched cardiomyocyte
      enriched pellet preparations. Similar to our findings in the murine study, we
      found that CNP-dependent GC activity was about half of the ANP-dependent GC
      activity in the non-failing ventricular and was increased in the failing
      ventricle. ANP and CNP increased GC activity 9- and 5-fold in non-failing
      ventricles, respectively. In contrast to the mouse study, in failing human
      ventricles, ANP-dependent activity was unchanged compared to non-failing values
      whereas CNP-dependent activity increased 35% (p=0.005). Compared with ventricular
      membranes, basal GC activity was reduced an order of magnitude in membranes
      derived from myocyte-enriched pellets from non-failing ventricles. ANP increased
      GC activity 2.4-fold but CNP only increased GC activity 1.3-fold. In contrast,
      neither ANP nor CNP increased GC activity in equivalent preparations from failing
      ventricles. We conclude that: 1) GC-B activity is increased in non-myocytes from
      failing human ventricles, possibly as a result of increased fibrosis, 2) human
      ventricular cardiomyocytes express low levels of GC-A and much lower levels or
      possibly no GC-B, and 3) GC-A in cardiomyocytes from failing human hearts is
      refractory to ANP stimulation.

PMID- 22133376
TI  - Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty
      acids on liver fatty acid desaturases and transport proteins in Wistar rats.
AB  - A disturbed fatty acid metabolism increases the risk of adult non-communicable
      diseases. This study examines the effect of maternal micronutrients on the fatty
      acid composition, desaturase activity, mRNA levels of fatty acid desaturases and
      transport proteins in the liver. Pregnant female rats were divided into 6 groups
      at 2 levels of folic acid both in the presence and absence of vitamin B(12). The
      vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. An
      imbalance of maternal micronutrients reduces liver docosahexaenoic acid,
      increases Delta5 desaturase activity but decreases mRNA levels, decreases Delta6
      desaturase activity but not mRNA levels as compared to control. mRNA level of
      Delta5 desaturase reverts back to the levels of the control group as a result of
      omega 3 fatty acid supplementation. Our data for the first time indicates that
      maternal micronutrients differentially alter the activity and expression of fatty
      acid desaturases in the liver.

PMID- 22133377
TI  - Molecular cloning and characterization of the NADPH oxidase from the kuruma
      shrimp, Marsupenaeus japonicus: early gene up-regulation after Vibrio penaeicida
      and poly(I:C) stimulations in vitro.
AB  - Free radicals such as nitric oxide (NO) and reactive oxygen species (ROS) are
      involved in many physiological processes. In humans, there are 5 homologs of
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Noxes) that
      generate superoxide (O(2)(-)), which can dismute to produce ROS, and play
      significant roles in innate immunity and cell proliferation. Though Noxes have
      been identified in vertebrates (humans and fishes) and some insects, there are
      very few reports investigating Noxes in crustaceans. In the present study, we
      describe the entire cDNA sequence (4216 bp) of Marsupenaeus japonicus (kuruma
      shrimp) Nox (MjNox) generated using reverse transcriptase-polymerase chain
      reaction (RT-PCR) and random amplification of cDNA ends (RACE). The open reading
      frame of MjNox encodes a protein of 1280 amino acids with an estimated mass of
      146 kDa that has 46.8% sequence homology with the Nox gene of the fruit fly,
      Drosophila melanogaster. Highly conserved amino acid sequences were observed in
      the NADPH binding domain. Transcriptional analysis revealed that MjNox mRNA is
      highly expressed in the lymphoid organ, hepatopancreas and hemocytes of the
      healthy kuruma shrimp. In the hemocytes, MjNox expression reached its peak 4 h
      after stimulation with either Vibrio penaeicida or poly(I:C) and decreased to its
      normal level after 12 h.This study is the first to identify and clone a Nox
      family member (MjNox) from a crustacean species.

PMID- 22133378
TI  - Characterizing the citrus cultivar Carrizo genome through 454 shotgun sequencing.
AB  - The citrus cultivar Carrizo is the single most important rootstock to the US
      citrus industry and has resistance or tolerance to a number of major citrus
      diseases, including citrus tristeza virus, foot rot, and Huanglongbing (HLB,
      citrus greening). A Carrizo genomic sequence database providing approximately
      3.5*genome coverage (haploid genome size approximately 367 Mb) was populated
      through 454 GS FLX shotgun sequencing. Analysis of the repetitive DNA fraction
      indicated a total interspersed repeat fraction of 36.5%. Assembly and
      characterization of abundant citrus Ty3/gypsy elements revealed a novel type of
      element containing open reading frames encoding a viral RNA-silencing suppressor
      protein (RNA binding protein, rbp) and a plant cytokinin riboside 5'
      monophosphate phosphoribohydrolase-related protein (LONELY GUY, log). Similar
      gypsy elements were identified in the Populus trichocarpa genome. Gene-coding
      region analysis indicated that 24.4% of the nonrepetitive reads contained genic
      regions. The depth of genome coverage was sufficient to allow accurate assembly
      of constituent genes, including a putative phloem-expressed gene. The development
      of the Carrizo database (http://citrus.pw.usda.gov/) will contribute to
      characterization of agronomically significant loci and provide a publicly
      available genomic resource to the citrus research community.

PMID- 22133379
TI  - Postoperative insole-paedobarographic gait analysis for patients with flap
      coverages of weight-bearing and non-weight-bearing areas of the foot.
AB  - Functional results regarding shoe modifications, gait analysis and long-term
      durability of the reconstructed foot have not been reported using insole
      paedobarography. This article presents insole-paedobarographic gait analysis and
      discusses the various pressure distribution patterns following the reconstruction
      of the foot. This retrospective study reports on the clinical and functional
      results in 23 out of 39 patients who received flap coverage of their feet in our
      department in the period from 2001 to 2010. Mean follow-up time amounted to 46.6
      months. Patients were separated into two groups, those with flap coverage to the
      sole of the foot (group 1) and those with flap coverage to non-weight-bearing
      areas of the foot (group 2). Gait analysis was accomplished by using insole
      paedobarography. The results of the gait analysis have shown that in both patient
      groups, when comparing affected feet with sound feet, the affected feet were
      exposed to significantly less support time (group 1; affected vs. sound feet:
      0.44 +/- 0.07 s vs. 0.55 +/- 0.11 s, p = 0.047), (group 2; affected vs. sound
      feet: 0.47 +/- 0.07 s vs. 0.54 +/- 0.07 s, p = 0.029). In addition, in both
      patient groups, the analysis of peak-pressure distributions revealed greater
      pressures on the affected feet compared to the sound feet (group 1; affected vs.
      sound feet: 47.9 +/- 10.13 N cm(-2) vs. 36.3 +/- 7.5 N cm(-2), p = 0.008), (group
      2; affected vs. sound feet: 38.08 +/- 13.98 N cm(-2) vs. 32.92 +/- 14.77 N cm(
      2), p = 0.061). The insole paedobarography can contribute to a more precise gait
      analysis following a soft-tissue reconstruction not only of the sole but also of
      other foot regions as well. It can help to identify and correct movement
      sequences and peak-pressure distributions which are damaging to the flaps. The
      resulting potential minimisation of the ulceration rate can lead to a further
      optimisation in the rate of completely rehabilitated patients and a reduction in
      the revision rate.

PMID- 22133380
TI  - Paraspinous muscle flap for the treatment of an empyema cavity.
AB  - For the reconstruction of defects localised near the midline region of the back,
      there have been occasional reports of reconstruction using a paraspinous muscle
      flap; however, to the best of our knowledge, there have been no reports of
      empyema space reconstruction using a paraspinous muscle flap. A patient who
      developed empyema after a pulmonary lobectomy and in whom a paraspinous muscle
      flap was used to reconstruct a dead space in the medial region of the upper back
      created by fenestration is presented. The dead space was filled sufficiently, and
      the patient had a favourable course without complications. Although the rotation
      arc of the paraspinous muscle flap is limited, the flap's blood flow is stable,
      and flap elevation is easy and less invasive. The paraspinous muscle flap is
      useful for filling and closing a defect near the midline region of the back.

PMID- 22133381
TI  - The deleterious impact of primary care-based commissioning on plastic surgery
      services and patients.
AB  - The wide variation in the availability of treatments across the National Health
      Service (NHS) in England has led to a postcode lottery due to the rationing of
      available services by individual Primary Care Trusts (PCTs). In 2005 an NHS
      Modernisation Agency document, "Action on Plastic Surgery" was designed to aid
      PCTs making funding decisions on Plastic Surgery patients. Despite this and
      evidence in the Plastic Surgery literature, patients continue to experience
      difficulties in the primary care setting accessing our services.(3) The authors
      present two patients who presented to their GPs requesting to seen by the local
      Plastic Surgery service regarding their symptoms in an effort to explore the
      possible available treatment modalities. These patients were not referred and
      subsequently these patients operated upon themselves leading to complications
      which warranted inpatient management.

PMID- 22133382
TI  - Free-flap harvesting from paralytic limbs of poliomyelitis patients--a safe and
      feasible option.
AB  - BACKGROUND: Many patients who had childhood poliomyelitis are still suffering
      from the late sequalae of the condition. Free-flap harvesting from the paralytic
      limbs from these patients is a logical approach for functional preservation.
      However, concerns have been raised regarding its safety due to its hypoplastic
      vascular system and potential donor site healing problems. CASE REPORT: A 53-year
      old man with known childhood poliomyelitis presented with left facial sarcoma.
      After wide excision, the defect was reconstructed with a dual-island
      fasciocutaneous-free anterolateral thigh flap harvested from his paralytic limb.
      The pedicle and perforators were found to be no different from those in normal
      limbs. His recovery was smooth without complications. CONCLUSIONS: On the basis
      of our experience and current evidence in the literature, we believe that free
      flap harvesting from the paralytic lower limb in poliomyelitis patients is a safe
      option that incurs no additional risk and allows maximal function preservation.

PMID- 22133383
TI  - Experimental study on the microsurgical or spontaneous formation of lympho
      lymphonodular anastomoses in the rat model.
AB  - BACKGROUND: The restoration of the lymphatic function in chronic lymphoedemas can
      be achieved by microsurgical lymphatic vessel transplantation. Usually, end-to
      end anastomoses are performed between the lymphatic vessels. Sometimes, the lack
      of appropriate lymphatic recipient vessels impels the idea of connecting the
      grafts to local lymph nodes. This study focusses on the microsurgical completion
      of durable lympho-lymphonodular anastomoses and further the detection of a
      spontaneous formation. METHODS: In 36 Sprague-Dawley rats the retroperitoneal
      lymphatic structures were prepared after staining with patent blue V dye. In
      group A (n = 12), the left lumbar trunk was cut cranially and its distal part was
      turned over to the right lumbar lymph node where a microsurgical lympho
      lymphonodular anastomosis was performed. In group B (n = 12), treatment was
      similar but without anastomosing. In group C (n = 12), the left lumbar trunk was
      transected and the capsule of the contralateral lumbar lymph node was incised.
      Finally, the lumbar region was re-exposed and the lymphatic drainage was examined
      using patent blue in four animals of each group after 8, 12 and 16 weeks,
      respectively, to examine the development of possible spontaneous formations of
      lymphatic connections. RESULTS: In 12/12 animals of group A, patent transposed
      lymph vessels and anastomoses with blue staining of the right lumbar lymph node
      were observed. Only 1/12 animals of group B and 2/12 animals of group C showed a
      blue staining of the right lumbar lymph node. CONCLUSIONS: The microsurgical
      fabrication of lympho-lymphonodular anastomoses leads to a safe and durable
      lymphatic connection. The known plasticity of lymphatic vessels with the
      potential of spontaneous anastomosing seems to be higher between lymphatic
      vessels than between lymphatic vessels and a lymph node.

PMID- 22133384
TI  - The propeller flap concept used in vaginal wall reconstruction.
AB  - Most posterior vaginal wall defects are due to abdominoperineal resection for
      colorectal carcinoma involving the posterior vaginal wall or resection of local
      malignancies. The rectus abdominis myocutaneous flap, the modified Singapore flap
      and the gracilis myocutaneous flap remain workhorse solutions for this type of
      vaginal reconstruction. The introduction of the perforator concept has introduced
      new therapeutic options using the gluteal donor site region. Recently, perforator
      based gluteal flaps have been described as a reliable solution for reconstruction
      of posterior vaginal wall defects, with low donor site morbidity. Here, we
      present a new technique to optimise results and minimise morbidity to the
      patient.

PMID- 22133386
TI  - Tipranavir in the protease inhibitors arena.

PMID- 22133387
TI  - Incidence and risk of severe neutropenia in advanced cancer patients treated with
      cetuximab: a meta-analysis.
AB  - BACKGROUND AND AIM: Neutropenia is a serious adverse event for patients who are
      treated with cetuximab, an inhibitor of endothelial growth factor receptor.
      However, there is no consistent result of the relationship between cetuximab and
      neutropenia in randomized controlled trials (RCTs). We did a systematic review
      and meta-analysis of published RCTs to assess the overall risk of neutropenia
      associated with cetuximab. METHODS: PubMed, Cochrane Central Register of
      Controlled Trials, EMBASE, and American Society of Clinical Oncology conferences
      were searched for relevant RCTs. Quantitative and qualitative analyses were
      carried out to evaluate the association between neutropenia and cetuximab. Both
      the fixed-effect model and random-effects model were used. RESULTS: A total of
      7186 patients with a variety of advanced cancers from 14 trials were included in
      our analysis. The overall incidence of neutropenia in patients receiving
      cetuximab was 33% (95% CI 26, 43). Patients treated with cetuximab had a
      significantly increased risk of neutropenia compared with patients treated with
      control medication, with a relative risk (RR) of 1.12 (95% CI 1.05, 1.19; fixed
      effect model). Risk varied with tumor type. Higher risks were observed in
      patients with colorectal carcinoma (RR 1.17; 95% CI 1.04, 1.32; fixed-effect
      model) and non-small cell lung cancer (RR 1.07; 95% CI 0.99, 1.16; fixed-effect
      model). CONCLUSION: Cetuximab is associated with a significant risk of
      neutropenia in patients with advanced cancer receiving concurrent chemotherapy.

PMID- 22133388
TI  - Efficacy, safety, and palatability of RACTAB((r)) formulation amlodipine orally
      disintegrating tablets.
AB  - OBJECTIVE: The aim of this study was to confirm the efficacy, safety, and
      expected palatability of amlodipine orally disintegrating tablets (ODT)
      [RACTAB((r)) formulation (Towa, Osaka, Japan)]. We report the re-analyzed results
      of 1687 cases in clinical settings obtained through postmarketing surveillance in
      Japan. METHOD: Study subjects were patients receiving treatment for the first
      time with amlodipine ODT for hypertension under routine care. A multicenter
      central registration system was used for this prospective survey. The survey was
      conducted from October 2008 to October 2010. The observational period was 12
      weeks, during which time surveys on outpatient blood pressure, adverse events,
      palatability, etc. were conducted. RESULTS: Blood pressure stabilized following
      treatment, and both systolic and diastolic blood pressures were favorably
      controlled. Adverse events observed were not significantly different from those
      observed during drug use trials of amlodipine formulations reported in 2003.
      Moreover, palatability of amlodipine ODT showed a 99.6% (227 of 228 cases)
      favorable patient acceptance, which is consistent with the initial design concept
      of RACTAB((r)) formulation. CONCLUSIONS: The results of this postmarketing
      surveillance study indicated that the efficacy, safety, and palatability of
      amlodipine ODT met our expectations (dissolves quickly in the mouth, tastes good,
      and is not rough on the tongue). Accordingly, amlodipine ODT are believed to be
      an easy-to-use formulation for prescribing doctors, dispensing pharmacists, and
      patients receiving treatment.

PMID- 22133389
TI  - A single appointment protocol to create a partially edentulous CAD/CAM guided
      surgical template: a clinical report.
AB  - The traditional technique for creating a CAD/CAM surgical template with a
      NobelGuide protocol is to fabricate a radiographic template that depicts the
      planned tooth position first. Multiple appointments are needed for the
      fabrication of the radiographic template with Cone Beam Computed Tomography
      (CBCT) before the surgical procedure can start. An alternative technique is
      described for fabricating a radiographic template at the initial examination
      appointment and capturing the necessary DICOM data to plan and fabricate a
      CAD/CAM surgical template in a 1-appointment protocol, thereby saving the patient
      and clinician time and reducing the need for multiple appointments.

PMID- 22133390
TI  - Prosthodontic treatment of a patient taking nitrogen-containing bisphosphonates
      to preserve the integrity of the epithelial attachment: a clinical report.
AB  - Osteonecrosis of the jaw has been identified in recent years as an unfortunate
      potential side effect for patients taking nitrogen-containing bisphosphonates.
      Many authors have attempted unsuccessfully to elucidate the mechanism behind this
      drug-induced malady, leaving dentists with unclear guidelines on how to treat
      these patients. Recent literature suggests a threshold-related impairment of
      epithelial cell migration over bone. A conservative, non-invasive approach aimed
      at preserving the epithelial attachment in a patient on a long-term oral
      alendronate protocol is described. The advantage of this approach is to prevent a
      highly destructive bone degenerative process that does not have a clear and
      predictable treatment protocol.

PMID- 22133391
TI  - Oromandibular dystonia: a clinical report.
AB  - Oromandibular dystonia (OMD) consists of prolonged spasms caused by contraction
      of the muscles of the mouth and mandible and involves the muscles of mastication,
      facial expression, tongue, and eye lids. A multidisciplinary treatment approach
      is presented including the fabrication of a dental prosthesis to reduce/eliminate
      the symptoms of OMD. Etiology and treatment issues are discussed, emphasizing the
      importance of an interdisciplinary treatment approach.

PMID- 22133392
TI  - A risk assessment treatment planning protocol for the four implant immediately
      loaded maxilla: preliminary findings.
AB  - STATEMENT OF PROBLEM: There is debate as to the efficacy of maxillary complete
      arch reconstructions when only 4 implants are used. PURPOSE: The purpose of this
      study was to determine what risk factors, if any, may increase the likelihood for
      implant failure in immediate function by using a tilted distal, 4-implant
      approach in the maxilla. MATERIAL AND METHODS: A retrospective analysis of
      implant performance was conducted for patients treated with 4 implants placed in
      285 maxillae (1140 implants) and 273 mandibles (992 implants) providing immediate
      function for complete arch implant-supported prostheses. The consecutively
      treated patient cohort consisted of those who provided consent between April 2008
      and December 2010. A retrospective chart review was conducted to assess potential
      maxillary implant failure factors, including a history of smoking, gender,
      opposing occlusion, bone density, bone volume, insertion torque, parafunction,
      failed implant site, addiction, and systemic factors. Data were analyzed with
      descriptive statistics. A series of risk factors were postulated in an effort to
      establish guidelines for modification of treatment planning protocols in response
      to combined risks. RESULTS: Several common primary factors in maxillary implant
      failure scenarios were identified through this process of patient profiling.
      Opposing natural dentition, male gender, lack of bone density, the distal implant
      site, and parafunction were sufficiently frequent occurrences in failure
      situations to suggest that either the use of additional implants or delayed
      loading and the provision of a complete denture as an interim prosthesis may be
      more appropriate in the management of patients identified as being high risk.
      Secondary factors such as bone availability (volume) and smoking were less common
      in failure situations. CONCLUSIONS: A preliminary protocol is suggested for both
      treatment planning and profiling patients with respect to presenting
      characteristics that may contribute to implant failure. A decrease in failure
      occurrence has been noted anecdotally during the short term implementation of
      this protocol.

PMID- 22133393
TI  - An in vitro assessment of circumferential grooves on the retention of cement
      retained implant-supported crowns.
AB  - STATEMENT OF PROBLEM: Crowns cemented on short implant abutments may have
      insufficient retention. PURPOSE: The purpose of this study was to evaluate the
      effect of circumferential grooves on the retention of cemented cast copings on
      implant abutments. MATERIAL AND METHODS: Sixty similarly-shaped implant abutments
      were divided into 4 groups (n=15): without grooves, with 1 groove, with 2
      grooves, and with 3 grooves. Fifteen identical NiCr cast copings were prepared to
      fit all 60 abutments. The castings were cemented to each group of abutments with
      a noneugenol provisional cement (Tempbond NE) and a zinc phosphate cement
      (Harvard). After thermal cycling and storage for 6 days in a water bath,
      retention tests were conducted with a tensile testing machine (Instron) (5
      mm/min) and retentive forces were recorded. Data were subjected to 1 way-ANOVA,
      Tukey's (HSD) test, and repeated measures ANOVA (alpha=.05). RESULTS: For the
      noneugenol temporary cement, group retention values were increased according to
      the number of grooves (P<.001). For the zinc phosphate cement, the first groove
      increased the retention by approximately 60% (P<.001). The retentive values were
      higher for the zinc phosphate cement than the provisional cement. The influence
      of the grooves depended on the type of cement used (P<.001). Cement remnants were
      found primarily on the castings for provisional cement and for the plain
      abutments cemented with zinc phosphate cement. Remnants were found primarily on
      the abutments for the grooved abutments cemented with zinc phosphate cement.
      CONCLUSIONS: The addition of circumferential grooves to implant abutments
      increased the retention of cement-retained castings. For zinc phosphate cement, 1
      groove was as effective as several, whereas for the provisional cement, the
      retention increased gradually with additional grooves.

PMID- 22133394
TI  - The effect of E-glass fibers and acrylic resin thickness on fracture load in a
      simulated implant-supported overdenture prosthesis.
AB  - STATEMENT OF PROBLEM: Implant overdenture prostheses are prone to acrylic resin
      fracture because of space limitations around the implant overdenture components.
      PURPOSE: The purpose of this study was to evaluate the influence of E-glass
      fibers and acrylic resin thickness in resisting acrylic resin fracture around a
      simulated overdenture abutment. MATERIAL AND METHODS: A model was developed to
      simulate the clinical situation of an implant overdenture abutment with varying
      acrylic resin thickness (1.5 or 3.0 mm) with or without E-glass fiber
      reinforcement. Forty-eight specimens with an underlying simulated abutment were
      divided into 4 groups (n=12): 1.5 mm acrylic resin without E-glass fibers
      identified as thin with no E-glass fiber mesh (TN-N); 1.5 mm acrylic resin with E
      glass fibers identified as thin with E-glass fiber mesh (TN-F); 3.0 mm acrylic
      resin without E-glass fibers identified as thick without E-glass fiber mesh (TK
      N); and 3.0 mm acrylic resin with E-glass fibers identified as thick with E-glass
      fiber mesh (TK-F). All specimens were submitted to a 3-point bending test and
      fracture loads (N) were analyzed with a 2-way ANOVA and Tukey's post hoc test
      (alpha=.05). RESULTS: The results revealed significant differences in fracture
      load among the 4 groups, with significant effects from both thickness (P<.001)
      and inclusion of the mesh (P<.001). Results demonstrated no interaction between
      mesh and thickness (P=.690). The TN-N: 39 +/-5 N; TN-F: 50 +/-6.9 N; TK-N: 162 +/
      13 N; and TK-F: 193 +/-21 N groups were all statistically different (P<.001).
      CONCLUSIONS: The fracture load of a processed, acrylic resin implant-supported
      overdenture can be significantly increased by the addition of E-glass fibers even
      when using thin acrylic resin sections. On a relative basis, the increase in
      fracture load was similar when adding E-glass fibers or increasing acrylic resin
      thickness.

PMID- 22133395
TI  - Effects of metal primers on the bonding of an adhesive resin cement to noble
      metal ceramic alloys after thermal cycling.
AB  - STATEMENT OF PROBLEM: Although the effectiveness of primers for resin bonding to
      noble alloys has been demonstrated, no effective clinical technique for bonding
      to noble metal ceramic alloys has been established. PURPOSE: The purpose of this
      study was to evaluate the effects of metal primers on the shear bond strength of
      an adhesive resin to noble metal ceramic alloys after thermal cycling. MATERIAL
      AND METHODS: Sixty-three disk-shaped specimens (10 * 2.5 mm) were cast from high
      gold-content alloys (Super Metal W-85: W85 or IFK88 GR: IFK88), a high-palladium
      content alloy (Super Metal N-40: N40), and an Ag-Pd-Cu-Au alloy (Castwell M.C.12:
      MC12). Smaller-sized disk-shaped specimens (8 * 2.5 mm) were fabricated with
      MC12. Bonding surfaces were finished with 600-grit SiC-paper and airborne
      particle abraded with 50-MUm alumina. Pairs of disks were primed (V-Primer: VP;
      ML Primer: ML; or Metaltite: MT) and bonded with an adhesive resin (Super-Bond
      C&B). The bond strengths were determined before and after 20,000 and 50,000
      thermal cycles (n=7). Data were analyzed by using a 3-way ANOVA and the
      Bonferroni test (alpha=.05). Failure modes were determined by optical microscope
      and SEM observation. RESULTS: Bond strengths to high-gold-content alloys with VP
      and MT significantly decreased after the thermal cycling (P<.001). Bond strengths
      to W85 (35.27 +/-4.25 MPa) and IFK88 (33.57 +/-3.56 MPa) after 50,000 thermal
      cycles obtained by ML were the highest (P<.001), and these groups showed
      combination failures. Bond strengths to N40 significantly decreased after 50,000
      thermal cycles (P<.001), regardless of primers. CONCLUSIONS: Shear bond strengths
      (SBS) to high-gold-content alloys were not degraded up to 50,000 thermal cycles
      when primed with ML. None of the primers evaluated was effective for high
      palladium-content alloy.

PMID- 22133396
TI  - The impact of in vitro aging on the mechanical and optical properties of indirect
      veneering composite resins.
AB  - STATEMENT OF PROBLEM: Flexural strength, hardness, surface roughness,
      discoloration, and abrasion resistance are important properties of veneering
      composite resins. Recently introduced veneering resins are purported to have
      enhanced mechanical properties due to their composition, but their long-term
      durability is not known. PURPOSE: The purpose of this study was to test the
      impact of aging on 3 different veneering composite resins. MATERIAL AND METHODS:
      Indirect composite resins, GC Gradia, VITA VM LC, and Sinfony were prepared for
      flexural strength (n=165 per group), Martens hardness (n=10), surface roughness
      (n=10), discoloration measurement (n=30), and abrasion resistance (n=6) testing.
      After initial flexural strength measurement, the remaining specimens were stored
      in water or subjected to thermocycling for 1, 7, 28, 90, or 180 days, and
      hardness and surface roughness (water stored: n=5 and thermocycling: n=5) were
      tested. The discoloration specimens were divided into 3 groups: coffee, black
      tea, and red wine; n=10), and age and discoloration were measured. Abrasion
      resistance was determined after 120,000, 240,000, 640,000, and 1,200,000
      mechanical thermocycling loading. One-way ANOVA was used, followed by a post hoc
      Scheffe test and t test. The longitudinal observations were analyzed by using
      linear mixed models (alpha=.05). RESULTS: When considering all 5 of the
      properties tested, Sinfony demonstrated the best results, followed by GC Gradia
      and VITA VM LC. CONCLUSIONS: The veneering composite resin, Sinfony, showed the
      most stable properties.

PMID- 22133397
TI  - Accuracy of rapid prototype models for head and neck reconstruction.
AB  - STATEMENT OF PROBLEM: Rapid prototype (RP) models are used in craniofacial
      reconstructions; however, there are no standards or acceptable limits to ensure
      accuracy of the fabricated models. PURPOSE: The purpose of this study was to
      assess the accuracy of RP models by validating the accuracy of SLA skull models
      with a coordinate measurement device. MATERIAL AND METHODS: Stainless steel
      spheres were located on a dry cadaver skull as fiducial markers, scanned with
      Multi Detector Computer Tomography (MDCT), and interpreted with software for
      rapid prototyping. Seven stereolithographic (SLA) models were fabricated and
      measured with a coordinate measurement device. An Euler rotation transformation
      calculation was applied to standardize the coordinate system between the control
      and the models. A paired standard t test (alpha=.05) was used to compare fiducial
      marker locations on SLA models with the control. RESULTS: A significant
      difference was found between the control and each of the SLA models (P<.001) in
      the Z axis additive build. Significant dimensional differences were not
      consistently detected in the X and Y axes. Dimensional deviations fell within the
      size of the MDCT scans voxel dimensions. CONCLUSIONS: The greatest discrepancies
      of medical model fabrication correspond to the largest dimension of the
      orthotropic voxel volume of the MDCT scan, which is related to the slice
      thickness of the scan and the Z axis of the RP model. However, the absolute
      magnitude of the error was small, well within the generally accepted tolerance
      for patient treatment.

PMID- 22133398
TI  - Fabrication of a cast-based implant surgical guide using guide sleeves.
AB  - A unique method for fabricating cast-based surgical guides is presented. A
      proposed position and mesiodistal angulation of the implant are verified with
      periapical radiography and registered with a commercially available guide sleeve.
      The sleeve is attached to a surgical guide made of light-polymerized acrylic
      resin. The surgical guide can be used in a broad range of situations and allows
      for accurate implant placement in a prosthetically driven position with surgical
      access and visibility, simplicity, and cost efficiency.

PMID- 22133399
TI  - Fluency disorders and a commitment to rigorous research.

PMID- 22133400
TI  - Journal of Fluency Disorders. Editorial.

PMID- 22133401
TI  - The Public Opinion Survey of Human Attributes--Stuttering (POSHA-S): summary
      framework and empirical comparisons.
AB  - PURPOSE: The Public Opinion Survey of Human Attributes-Stuttering (POSHA-S) was
      developed to make available worldwide a standard measure of public attitudes
      toward stuttering that is practical, reliable, valid, and translatable. Mean data
      from past field studies as comparisons for interpretation of POSHA-S results are
      reported. METHOD: Means for POSHA-S items (converted to -100 to +100 scales),
      components comprising clusters of items, subscores comprising clusters of
      components, and Overall Stuttering Scores comprising two subscores for stuttering
      were generated from 64 samples, totaling 2876 respondents who completed
      experimental versions of the POSHA-S. DISCUSSION: Lowest, highest, and median
      sample values, which vary with the addition of new sample data to the growing
      POSHA-S database archive, provide points of comparison for any potential sample
      rather than predetermined values. CONCLUSIONS: The final POSHA-S, together with
      an ongoing and growing archive, can provide increasingly meaningful comparisons
      for stakeholders measuring public attitudes toward stuttering. EDUCATIONAL
      OBJECTIVES: (1) Describe the subscores and components of the POSHA-S, (2)
      describe the Overall Stuttering Score of the POSHA-S, and (3) describe the format
      for interpretation of the POSHA-S.

PMID- 22133402
TI  - Public attitudes toward stuttering in Turkey: probability versus convenience
      sampling.
AB  - PURPOSE: A Turkish translation of the Public Opinion Survey of Human Attributes
      Stuttering (POSHA-S) was used to compare probability versus convenience sampling
      to measure public attitudes toward stuttering. METHOD: A convenience sample of
      adults in Eskisehir, Turkey was compared with two replicates of a school-based,
      probability cluster sampling scheme. RESULTS: The two replicates of the
      probability sampling scheme yielded similar demographic samples, both of which
      were different from the convenience sample. Components of subscores on the POSHA
      S were significantly different in more than half of the comparisons between
      convenience and probability samples, indicating important differences in public
      attitudes. CONCLUSIONS: If POSHA-S users intend to generalize to specific
      geographic areas, results of this study indicate that probability sampling is a
      better research strategy than convenience sampling. EDUCATIONAL OBJECTIVES: The
      reader will be able to: (1) discuss the difference between convenience sampling
      and probability sampling; (2) describe a school-based probability sampling
      scheme; and (3) describe differences in POSHA-S results from convenience sampling
      versus probability sampling.

PMID- 22133403
TI  - Developing physiologic stress profiles for school-age children who stutter.
AB  - PURPOSE: Physiologic reactivity profiles were generated for 9 school-age children
      with a history of stuttering. Utilizing salivary sampling, stress biomarkers
      cortisol and alpha-amylase were measured in response to normal daily stressors.
      Children with a history of stuttering were characterized as high or low autonomic
      reactors when compared to age-normed references established for cortisol and
      alpha-amylase levels. METHOD: Salivary samples were collected four times daily
      over three consecutive days from children (6 boys and 3 girls) aged 6-11 years.
      Samples were measured for two important stress biomarkers, cortisol and alpha
      amylase. Following laboratory training on appropriate sampling technique using
      the Salivette, families collected all samples in their homes. RESULTS: Compared
      to published references established for normal children, children with a history
      of stuttering exhibited mean cortisol and alpha-amylase levels that were
      significantly lower, though within normal limits. CONCLUSIONS: Results reflect an
      initial investigation into the use of salivary sampling to measure reactivity in
      children who stutter. As children who stutter have historically been excluded
      from physiologic stress studies, salivary sampling appears to provide an
      innovative and minimally invasive option for investigators. Though interpreted
      with caution secondary to the small sample size, initial findings suggest that in
      response to normal daily stressors, school-age children with a history of
      stuttering do not exhibit significantly elevated stress biomarkers. EDUCATIONAL
      OBJECTIVES: The reader will be able to: (1) identify two biomarkers that reflect
      activation of the body's stress response; (2) discuss possible implications the
      generation of individualized stress profiles may have on the treatment of
      stuttering; and (3) discuss and evaluate the research needs associated with the
      inclusion of children in physiological studies of fluency.

PMID- 22133404
TI  - Group therapy for school-aged children who stutter: a survey of current
      practices.
AB  - Although group therapy is recommended for school-aged children who stutter (CWS),
      it is not widely researched. This study aimed to explore this provision, using a
      postal survey which investigated the current practices of Speech & Language
      Therapists (SLTs) in the UK. Seventy percent of SLT services provided some group
      therapy, but the level of provision was variable. There was a lack of consensus
      on what the main aims of group therapy should be. Important barriers to group
      therapy provision were identified, including a perceived lack of clients'
      interest in group therapy, and insufficient numbers of clients able to travel to
      group venues. This study enhances the profession's understanding of the provision
      of group therapy for CWS by identifying patterns of service delivery and
      highlighting areas of need. EDUCATIONAL OBJECTIVES: Readers should be able to:
      (1) Provide a rationale for the provision of group therapy for school-aged CWS;
      (2) Summarize the factors affecting group therapy provision for school-aged CWS;
      (3) Summarize the aims of therapy identified by the respondents to this survey.

PMID- 22133405
TI  - Comparison of pausing behavior in children who stutter and children who have
      Asperger syndrome.
AB  - PURPOSE: The objective of this research was to compare the number and types of
      grammatical and non-grammatical silent pauses presented by stutterers and
      subjects with Asperger syndrome in their narratives. METHOD: Ten children who
      stutter and four participants with Asperger syndrome (mean ages of both groups 10
      years) were assessed at the Speech and Language Disorders Department of the
      Universidade Federal de Sao Paulo/Brasil. They narrated a story based on a pre
      selected sequence of pictures. They were filmed and their productions were
      analyzed using version 5.0.47 of Praat
      (http://www.fon.hum.uva.nl/praat/download_win.html). Silent intervals in the
      speech that ranged from 0.25 to 4s were considered pauses. The pauses were
      classified as grammatical and non-grammatical, depending on the words that
      preceded and followed them. RESULTS: Both groups presented grammatical and non
      grammatical pauses and the former predominated. The children with Asperger
      syndrome produced a greater number of pauses than the stutterers. EDUCATIONAL
      OBJECTIVES: The reader will be able to: (1) characterize the use of pauses in the
      oral narrative; (2) distinguish a grammatical pause from a non-grammatical pause
      regarding the use and function; (3) recognize the pattern of pause found in the
      two populations.

PMID- 22133406
TI  - Stuttering, cluttering, and phonological complexity: case studies.
AB  - The phonological complexity of dysfluencies in those who clutter and/or stutter
      may help us better understand phonetic factors in these two types of fluency
      disorders. In this preliminary investigation, cases were three 14-year-old males,
      diagnosed as a Stutterer, a Clutterer, and a Stutterer-Clutterer. Spontaneous
      speech samples were transcribed, coded for dysfluent words which were then
      matched to fluent words on grammatical class (i.e., function vs. content), number
      of syllables and word familiarity. An Index of Phonological Complexity was
      determined per word, and word frequency, density and phonological neighborhood
      frequency were derived from an online database. Results showed that compared to
      fluent words, dysfluent words were more phonologically complex and 'sparser',
      implying that they have fewer phonological neighbors or words in which a single
      phoneme is added, deleted or substituted. Interpretations and future directions
      for research regarding phonological complexity in stuttering and cluttering are
      offered. EDUCATIONAL OBJECTIVES: 1. The reader can list three key symptoms of
      cluttering. 2. The reader will define phonological neighborhood density and
      neighborhood frequency. 3. The reader can calculate the Index of Phonological
      Complexity (IPC) for a given word. 4. The reader can state two findings from the
      current study and how each relates to other studies of phonological complexity
      and fluency disorders.

PMID- 22133407
TI  - Self-help conferences for people who stutter: a qualitative investigation.
AB  - Self-help activities for people who stutter (PWS) have been gaining in
      popularity; however, there is a scarcity of evidence to support their utility in
      stuttering management. The purpose of this investigation was to understand the
      lived experience of individuals who attended a self-help conference(s) for PWS
      from the perspective of a PWS to learn its potential utility in stuttering
      management. The investigator used Interpretive Phenomenological Analysis (IPA) to
      systematically collect authentic data of this social phenomenon. Twelve
      participants were recruited from a self-help conference and the self-help
      community of PWS. Semi-structured interviews were conducted 4-18 months after
      each participant's last conference. Interviews were transcribed and analyzed.
      Themes were explained in investigator narratives and illustrated through
      participants' quotes. Interpreted themes of the experience of having attended a
      self-help conference(s) for PWS included: socializing opportunities with other
      PWS, affiliation, redefining oneself and post-conference disclosures. A
      conclusion of the study was that the experience of having attended a self-help
      conference(s) for PWS helped to minimize negative impact that stuttering can have
      on daily functioning. It appears that self-help conferences were perceived as a
      safer or "stutter-friendly" environment and promoted social interaction,
      relationship building, and community building through planned and unplanned
      activities. Another conclusion was that the experience of having attended self
      help conferences for PWS helped participants to communicate more easily. Reported
      increases in social activity and an "openness" about stuttering, suggest self
      help conferences' utility in stuttering management. These findings are supported
      by other studies about successful stuttering management and self-help activities
      for PWS. They have helped attendees who stutter to communicate more easily and
      suggest a reduction in the negative impact that stuttering has on their lives.
      EDUCATIONAL OBJECTIVES: The reader will be able to: (1) describe recurring themes
      associated with the lived experience having attended a self-help conference(s)
      for people who stutter (PWS) from the perspective of a group of adults who
      stutter, and (2) describe the potential benefits of attending self-help
      conferences for PWS in order to make appropriate evidence-based referrals to self
      help conferences for PWS.

PMID- 22133408
TI  - The European Clinical Specialization on Fluency Disorders (ECSF).
AB  - The European Clinical Specialization on Fluency Disorders (ECSF) project consists
      of one-year post-qualification fluency specialization training and a harmonized
      graduate fluency program. It was developed by eight European
      universities/colleges to provide the means whereby graduates would meet
      comparable standards of competence to practice in the field of fluency disorders.
      In this paper we describe criteria that guided the consortium in their decision
      making process to create an optimal learning environment for participants. A
      review of the first completed course cycle, with 23 international participants,
      is discussed. EDUCATIONAL OBJECTIVES: After reading this article, the reader will
      be able to: (1) articulate the rationale for development of the ECSF-course; (2)
      summarize the content of both the harmonized undergraduate fluency course and the
      postgraduate fluency specialization course; (3) summarize the benefits of the
      suggested model for fluency specialization.

PMID- 22133409
TI  - Functional brain activation differences in stuttering identified with a rapid
      fMRI sequence.
AB  - The purpose of this study was to investigate whether brain activity related to
      the presence of stuttering can be identified with rapid functional MRI (fMRI)
      sequences that involved overt and covert speech processing tasks. The long-term
      goal is to develop sensitive fMRI approaches with developmentally appropriate
      tasks to identify deviant speech motor and auditory brain activity in children
      who stutter closer to the age at which recovery from stuttering is documented.
      Rapid sequences may be preferred for individuals or populations who do not
      tolerate long scanning sessions. In this report, we document the application of a
      picture naming and phoneme monitoring task in 3 min fMRI sequences with adults
      who stutter (AWS). If relevant brain differences are found in AWS with these
      approaches that conform to previous reports, then these approaches can be
      extended to younger populations. Pairwise contrasts of brain BOLD activity
      between AWS and normally fluent adults indicated the AWS showed higher BOLD
      activity in the right inferior frontal gyrus (IFG), right temporal lobe and
      sensorimotor cortices during picture naming and higher activity in the right IFG
      during phoneme monitoring. The right lateralized pattern of BOLD activity
      together with higher activity in sensorimotor cortices is consistent with
      previous reports, which indicates rapid fMRI sequences can be considered for
      investigating stuttering in younger participants. EDUCATIONAL OBJECTIVES: The
      reader will learn about and be able to describe the: (1) use of functional MRI to
      study persistent developmental stuttering; (2) differences in brain activation
      between persons who stutter and normally fluent speakers; and (3) potential
      benefit of time efficient fMRI sequences combined with a range of speech
      processing tasks for investigating stuttering in younger populations.

PMID- 22133410
TI  - Reprint of: stuttering treatment control using P300 event-related potentials.
AB  - Positron emission tomography studies during speech have indicated a failure to
      show the normal activation of auditory cortical areas in stuttering individuals.
      In the present study, P300 event-related potentials were used to investigate
      possible effects of behavioral treatment on the pattern of signal amplitude and
      latency between waves. In order to compare variations in P300 measurements, a
      control group paired by age and gender to the group of stutterers, was included
      in the study. Findings suggest that the group of stutterers presented a
      significant decrease in stuttering severity after the fluency treatment program.
      Regarding P300 measurements, stutterers and their controls presented results
      within normal limits in all testing situations and no significant statistical
      variations between pre and post treatment testing. When comparing individual
      results between the testing situations, stutterers presented a higher average
      decrease in wave latency for the right ear following treatment. The results are
      discussed in light of previous P300 event-related potentials and functional
      imaging studies with stuttering adults. EDUCATIONAL OBJECTIVES: The reader will
      learn about and be able to describe the: (1) use of P300 event-related potentials
      in the study of stuttering; (2) differences between stuttering and non-stuttering
      adults; and (3) effects of behavioral fluency treatment on cerebral activity in
      stuttering speakers.

PMID- 22133411
TI  - Stuttering attitudes among Turkish family generations and neighbors from
      representative samples.
AB  - PURPOSE: Attitudes toward stuttering, measured by the Public Opinion Survey of
      Human Attributes-Stuttering (POSHA-S), are compared among (a) two different
      representative samples; (b) family generations (children, parents, and either
      grandparents or uncles and aunts) and neighbors; (c) children, parents,
      grandparents/adult relatives, and neighbors of the same family/neighbor units vs.
      individuals from different family/neighbor units; and (d) attitudes from one
      Turkish city with an international database archive. METHODS: Following a school
      based, three-stage, cluster probability sampling scheme, two sets of children,
      parents, grandparents/adult relatives, and neighbors (50 each) in Eskisehir,
      Turkey (PROB1 and PROB2) completed Turkish translations of the POSHA-S. The POSHA
      S measures attitudes toward stuttering within the context of other attributes,
      such as obesity and mental illness. RESULTS: Both replicates of the sampling
      procedure yielded strikingly similar attitudes for stuttering between children,
      parents, grandparents/adult relatives, and neighbors in PROB1 vs. PROB2, and
      between all pair-wise comparisons within PROB1 and PROB2. By contrast, attitudes
      toward obesity and mental illness were dissimilar. Correlations were small to
      moderate among attitudes of the same family/neighbor units but were essentially
      nonexistent between different family/neighbor units. Attitudes toward stuttering
      in Eskisehir were estimated to be less positive than attitudes from a wide range
      of samples around the world, although exceptions occurred. CONCLUSIONS: A school
      based probability sampling procedure yielded consistent findings that are likely
      different from results from convenience samples. Families appear to be an
      important influence in determining public attitudes toward stuttering and other
      human attributes. EDUCATIONAL OBJECTIVES: The reader will be able to: (i)
      identify similarities and differences among attitudes toward stuttering across
      generations; (ii) identify similarities and differences among attitudes toward
      stuttering in Turkey vs. other places in the world; (iii) describe a school-based
      probability sampling scheme; (iv) describe advantages of using a standard
      instrument to measure public attitudes toward stuttering.

PMID- 22133412
TI  - The accuracy with which adults who do not stutter predict stuttering-related
      communication attitudes.
AB  - The purpose of this study was to examine the extent to which adults who do not
      stutter can predict communication-related attitudes of adults who do stutter. 40
      participants (mean age of 22.5 years) evaluated speech samples from an adult with
      mild stuttering and an adult with severe stuttering via audio-only (n=20) or
      audio-visual (n=20) modes to predict how the adults had responded on the S24
      scale of communication attitudes. Participants correctly predicted which speaker
      had the more favorable S24 score, and the predicted scores were significantly
      different between the severity conditions. Across the four subgroups, predicted
      S24 scores differed from actual scores by 4-9 points. Predicted values were
      greater than the actual values for 3 of 4 subgroups, but still relatively
      positive in relation to the S24 norm sample. Stimulus presentation mode
      interacted with stuttering severity to affect prediction accuracy. The
      participants predicted the speakers' negative self-attributions more accurately
      than their positive self-attributions. Findings suggest that adults who do not
      stutter estimate the communication-related attitudes of specific adults who
      stutter in a manner that is generally accurate, though, in some conditions,
      somewhat less favorable than the speaker's actual ratings. At a group level,
      adults who do not stutter demonstrate the ability to discern minimal versus
      average levels of attitudinal impact for speakers who stutter. The participants'
      complex prediction patterns are discussed in relation to stereotype accuracy and
      classic views of negative stereotyping. EDUCATIONAL OBJECTIVES: The reader will
      be able to (a) summarize main findings on research related to listeners'
      attitudes toward people who stutter, (b) describe the extent to which people who
      do not stutter can predict the communication attitudes of people who do stutter;
      and (c) discuss how findings from the present study relate to previous findings
      on stereotypes about people who stutter.

PMID- 22133413
TI  - Speech sequence skill learning in adults who stutter.
AB  - The present study compared the ability of 12 people who stutter (PWS) and 12
      people who do not stutter (PNS) to consolidate a novel sequential speech task.
      Participants practiced 100 repetitions of a single, monosyllabic, nonsense word
      sequence during an initial practice session and returned 24-h later to perform an
      additional 50 repetitions. Results showed significantly slower sequence durations
      in the PWS compared to PNS following extensive practice and consolidation.
      However, the hypothesis that poor performance gains in PWS compared to PNS during
      practice would be maintained following a 24-h consolidation period was not
      supported. Further descriptive analysis revealed large within group differences
      in PWS which to some extent were attributed to a subgroup of PWS who failed to
      show any improvements in performance following practice or consolidation. The
      results and the possible presence of subgroups of PWS are discussed with regard
      to their limitations in motor learning abilities. EDUCATIONAL OBJECTIVES: The
      reader will be able to (1) explain the difference between practice and learning,
      (2) define consolidation and explain the importance of measuring performance
      following a consolidation period, (3) understand past research on PWS'
      performance during both speech and nonspeech motor tasks, and (4) explain why
      individual differences in practice effects and learning may have important
      implications for client variability in treatment outcome.

PMID- 22133414
TI  - Comparison between two human papillomavirus genotyping assays targeting the L1 or
      E6/E7 region in cervical cancer biopsies.
AB  - INTRODUCTION: Human papillomavirus (HPV) testing is increasingly used in cervical
      cancer prevention strategies, and a variety of HPV genotyping assays have been
      developed. We aimed to compare the performance of two HPV genotyping techniques
      in formalin-fixed paraffin-embedded (FFPE) tissue specimens from a series of
      invasive squamous cell carcinoma (SCC) cases. METHODS: Archival FFPE tissue
      blocks from 78 SCC cases were initially considered. DNA was extracted from
      dewaxed tissue sections and tested with the INNO-LiPA HPV Genotyping Extra assay
      (Innogenetics), and the F-HPV typing kit (Genomed) targeting the L1 and E6/E7
      regions, respectively. RESULTS: The INNO-LiPA assay showed a higher sensitivity
      (98.6%) than the F-HPV assay (78.6%). A total of 12 (17.1%) biopsies showed
      multiple-type infections evidenced by at least one assay. Among the SCC cases
      tested, HPV16 and/or 18 were detected in 70% of the cases, and 18.4% of them had
      multiple infections with other high-risk types. CONCLUSIONS: Our results suggest
      that the INNO-LiPA assay has a better performance than the F-HPV in FFPE
      specimens, probably due to its smaller amplicon size and the wider range of
      detectable HPV types. The prevalence of multiple infections could be higher than
      previously reported, as evidenced by the combination of the two assays.

PMID- 22133415
TI  - [Infections due to rapidly growing mycobacteria].
AB  - Rapidly growing mycobacteria (RGM) are ubiquitous in nature and widely
      distributed in water, soil and animals. During the past three decades we have
      observed a notable increment of infections caused by RGM, both localized and
      disseminated, as well as nosocomial outbreaks of contaminated medical equipment.
      The microbiological diagnosis of RGM infections includes direct microscopic
      observation and culture. The taxonomic identification is performed by phenotypic,
      biochemical, chromatographic and molecular biology techniques. The treatment
      differs from that of other mycobacteriosis like tuberculosis, owing to the
      variable in vitro susceptibility of the species of this group. The RGM are
      resistant to conventional antituberculous drugs, but can be susceptible to broad
      spectrum antimicrobial agents. In this study we comment on the significant
      aspects of human infections by RGM, including their biology, epidemiology,
      pathology, microbiological diagnosis, taxonomic identification, antimicrobial
      susceptibility and treatment.

PMID- 22133416
TI  - [Community-acquired cavitary pneumonia caused by Panton-Valentine leukocidin
      producing methicillin-resistant Staphylococcus aureus].

PMID- 22133417
TI  - Rate-limiting step of the Rh-catalyzed carboacylation of alkenes: C-C bond
      activation or migratory insertion?
AB  - Rhodium-catalyzed intramolecular carboacylation of alkenes, achieved using
      quinolinyl ketones containing tethered alkenes, proceeds via the activation and
      functionalization of a carbon-carbon single bond. This transformation has been
      demonstrated using RhCl(PPh(3))(3) and [Rh(C(2)H(4))(2)Cl](2) catalysts.
      Mechanistic investigations of these systems, including determination of the rate
      law and kinetic isotope effects, were utilized to identify a change in mechanism
      with substrate. With each catalyst, the transformation occurs via rate-limiting
      carbon-carbon bond activation for species with minimal alkene substitution, but
      alkene insertion becomes rate-limiting for more sterically encumbered substrates.
      Hammett studies and analysis of a series of substituted analogues provide
      additional insight into the nature of these turnover-limiting elementary steps of
      catalysis and the relative energies of the carbon-carbon bond activation and
      alkene insertion steps.

PMID- 22133418
TI  - Talking about sex to oncologists and cancer to sexologists.

PMID- 22133421
TI  - Predicting hospital cost in CKD patients through blood chemistry values.
AB  - BACKGROUND: Controversy exists in predicting costly hospitalization in patients
      with chronic kidney disease and co-morbid conditions. We therefore tested
      associations between serum chemistry values and the occurrence of in-patient
      hospital costs over a thirteen month study period. Secondarily, we derived a
      linear combination of variables to estimate probability of such occurrences in
      any patient. METHOD: We calculated parsimonious values for select variables
      associated with in-patient hospitalization and compared sensitivity and
      specificity of these models to ordinal staging of renal disease.Data from 1104 de
      identified patients which included 18 blood chemistry observations along with
      complete claims data for all medical expenses.We employed multivariable logistic
      regression for serum chemistry values significantly associated with in-patient
      hospital costs exceeding $3,000 in any single month and contrasted those results
      to other models by ROC area curves. RESULTS: The linear combination of weighted Z
      scores for parathyroid hormone, phosphorus, and albumin correlated with in
      patient hospital care at p<0.005. ROC curves derived from weighted variables of
      age, eGFR, hemoglobin, albumin, creatinine, and alanine aminotransferase
      demonstrated significance over models based on non-weighted Z scores for those
      same variables or CKD stage alone. In contrast, the linear combination of
      weighted PTH, PO4 and albumin demonstrated better prediction, but not
      significance over non-weighted Z scores for PTH alone. CONCLUSION: Further study
      is justified to explore indices that predict costly hospitalization. Such metrics
      could assist Accountable Care Organizations in evaluating risk adjusted
      compensation for providers.

PMID- 22133423
TI  - Total serum bilirubin exceeding exchange transfusion thresholds in the setting of
      universal screening.
AB  - OBJECTIVE: To describe the incidence and predictors of total serum bilirubin
      (TSB) levels that meet or exceed American Academy of Pediatrics (AAP) exchange
      transfusion (ET) thresholds in the setting of universal screening. STUDY DESIGN:
      We conducted a retrospective cohort analysis of electronic data on 18 089
      newborns >=35 weeks gestation born at Northern California Kaiser Permanente
      Medical Care Program hospitals implementing universal TSB screening in 2005 to
      2007, with chart review for subjects with TSB levels reaching the AAP threshold
      for ET. RESULTS: The outcome developed in 22 infants (0.12%); 14 (63.6%) were <38
      weeks gestation. Only one infant received an ET; none of the infants had
      documented sequelae. The first TSB was at least high-intermediate risk on the AAP
      risk-nomogram for all 22 infants and high-risk for those >=38 weeks, but was less
      than the phototherapy level in 15 infants (68%). Of these 15 infants, 2 failed
      phototherapy and 13 did not have a TSB repeated in <24 hours. However, re-testing
      all infants at high-intermediate risk or greater would have required 2166
      additional bilirubin tests. CONCLUSION: Screening was sensitive but not specific
      for predicting exchange threshold.

PMID- 22133422
TI  - Sleep-disordered breathing is associated with asthma severity in children.
AB  - OBJECTIVE: To examine the relationships among obesity, sleep-disordered breathing
      (SDB, defined as intermittent nocturnal hypoxia and habitual snoring), and asthma
      severity in children. We hypothesized that obesity and SDB are associated with
      severe asthma at a 1- year follow-up. STUDY DESIGN: Children aged 4-18 years were
      recruited sequentially from a specialty asthma clinic and underwent
      physiological, anthropometric, and biochemical assessment at enrollment. Asthma
      severity was determined after 1 year of follow-up and guideline-based treatment,
      using a composite measure of level of controller medication, symptom burden, and
      health care utilization. Multivariate logistic regression was used to examine
      adjusted associations of SDB and obesity with asthma severity at 12-month follow
      up. RESULTS: Among 108 subjects (mean age, 9.1+/-3.4 years; 45.4% African
      American; 67.6% male), obesity and SDB were common, affecting 42.6% and 29.6% of
      subjects, respectively. After adjusting for obesity, race, and sex, children with
      SDB had a 3.62-fold increased odds of having severe asthma at follow-up (95% CI,
      1.26-10.40). Obesity was not associated with asthma severity. CONCLUSION: SDB is
      a modifiable risk factor for severe asthma after 1 year of specialty asthma care.
      Further studies are needed to determine whether treating SDB improves asthma
      morbidity.

PMID- 22133424
TI  - Impact of type 1 diabetes mellitus on the family is reduced with the medical
      home, care coordination, and family-centered care.
AB  - OBJECTIVES: To examine whether the medical home, care coordination, or family
      centered care was associated with less impact of type 1 diabetes mellitus (T1D)
      on families' work, finances, time, and school attendance. STUDY DESIGN: With the
      2005 to 2006 National Survey of Children with Special Health Care Needs, we
      compared impact in children with T1D (n = 583) with that in children with other
      special health care needs (n = 39 944) and children without special health care
      needs (n = 4945). We modeled the associations of the medical home, care
      coordination, and family-centered care with family impact in T1D. RESULTS:
      Seventy-five percent of families of children with T1D reported a major impact
      compared with 45% of families of children with special health care needs (P <
      .0001) and 17% of families of children without special health care needs (P <
      .0001). In families of children with T1D, 35% reported restricting work, 38%
      reported financial impact, 41% reported medical expenses >$1000/year, 24%
      reported spending >=11 hours/week caring or coordination care, and 20% reported
      >=11 school absences/year. The medical home, care coordination, and family
      centered care were associated with less work and financial impact. CONCLUSIONS:
      In childhood T1D, most families experience major impact. Better systems of health
      care delivery may help families reduce some of this impact.

PMID- 22133425
TI  - Post-discharge adverse events following pediatric sedation with high doses of
      oral medication.
AB  - OBJECTIVE: To compare the occurrence of post-discharge adverse events in children
      having received a high dose of either chloral hydrate (CH) or midazolam (MZ)
      during outpatient dental treatment. STUDY DESIGN: A repeated-measures study
      design was carried out with 42 children treated at a sedation center. The sample
      comprised 103 dental sedation sessions among 22 male and 20 female patients, 1-8
      years old, receiving either MZ (1.0-1.5 mg/kg) or CH (70.0-100.0 mg/kg). During
      treatment, a single observer recorded intraoperative adverse events. Twenty-four
      hours later, the observer called the child's main caregiver seeking information
      on further adverse events. Data analysis involved descriptive and bivariate
      statistics and the general estimating equation for repeated measures. RESULTS:
      The most common intraoperative and post-discharge adverse events were
      hallucination (3.9%) and excessive sleep (41.9%), respectively. The chance of the
      occurrence of an adverse event following oral pediatric sedation was lesser among
      the children who received MZ than those who received CH (OR: 0.09; 95% CI: 0.01
      0.88). CONCLUSIONS: High doses of CH were associated with post-discharge adverse
      events in children having undergone pediatric dental sedation, whereas high doses
      of MZ were not associated with these events in pediatric patients.

PMID- 22133426
TI  - Contrasting signals of positive selection in genes involved in human skin-color
      variation from tests based on SNP scans and resequencing.
AB  - BACKGROUND: Numerous genome-wide scans conducted by genotyping previously
      ascertained single-nucleotide polymorphisms (SNPs) have provided candidate
      signatures for positive selection in various regions of the human genome,
      including in genes involved in pigmentation traits. However, it is unclear how
      well the signatures discovered by such haplotype-based test statistics can be
      reproduced in tests based on full resequencing data. Four genes (oculocutaneous
      albinism II (OCA2), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase
      (DCT), and KIT ligand (KITLG)) implicated in human skin-color variation, have
      shown evidence for positive selection in Europeans and East Asians in previous
      SNP-scan data. In the current study, we resequenced 4.7 to 6.7 kb of DNA from
      each of these genes in Africans, Europeans, East Asians, and South Asians.
      RESULTS: Applying all commonly used neutrality-test statistics for allele
      frequency distribution to the newly generated sequence data provided conflicting
      results regarding evidence for positive selection. Previous haplotype-based
      findings could not be clearly confirmed. Although some tests were marginally
      significant for some populations and genes, none of them were significant after
      multiple-testing correction. Combined P values for each gene-population pair did
      not improve these results. Application of Approximate Bayesian Computation Markov
      chain Monte Carlo based to these sequence data using a simple forward simulator
      revealed broad posterior distributions of the selective parameters for all four
      genes, providing no support for positive selection. However, when we applied this
      approach to published sequence data on SLC45A2, another human pigmentation
      candidate gene, we could readily confirm evidence for positive selection, as
      previously detected with sequence-based and some haplotype-based tests.
      CONCLUSIONS: Overall, our data indicate that even genes that are strong
      biological candidates for positive selection and show reproducible signatures of
      positive selection in SNP scans do not always show the same replicability of
      selection signals in other tests, which should be considered in future studies on
      detecting positive selection in genetic data.

PMID- 22133427
TI  - Open lumbosacral spine fractures with thecal sac ligation after combat blast
      trauma.

PMID- 22133428
TI  - Evoked dopamine overflow is augmented in the striatum of calcitriol treated rats.
AB  - Calcitriol, the active metabolite of vitamin D, has been shown to have
      significant effects on the brain. These actions include reducing the severity of
      some central nervous system lesions, possibly by upregulating trophic factors
      such as glial cell line-derived neurotrophic factor (GDNF). GDNF has substantial
      effects on the nigrostriatal dopamine (DA) system of young adult, aged and
      lesioned animals. Thus, the administration of calcitriol may lead to significant
      effects on nigrostriatal DA neuron functioning. The present experiments were
      designed to examine the ability of calcitriol to alter striatal DA release, and
      striatal and nigral tissue levels of DA. Male Fischer-344 rats were administered
      vehicle or calcitriol (0.3, 1.0, or 3.0 MUg/kg, s.c.) once daily for eight
      consecutive days. Three weeks later in vivo microdialysis experiments were
      conducted to measure basal and stimulus evoked overflow of DA from the striatum.
      Basal levels of extracellular DA were not significantly affected by the
      calcitriol treatments. However, the 1.0 and 3.0 MUg/kg doses of calcitriol led to
      increases in both potassium and amphetamine evoked overflow of striatal DA.
      Although post-mortem tissue levels of striatal DA were not altered by the
      calcitriol injections, nigral tissue levels of DA and its main metabolites were
      increased by both the 1.0 and 3.0 MUg/kg doses of calcitriol. In a separate group
      of animals GDNF levels were augmented in the striatum and substantia nigra after
      eight consecutive daily injections of calcitriol. These results suggest that
      systemically administered calcitriol can upregulate dopaminergic release
      processes in the striatum and DA levels in the substantia nigra. Increases in the
      levels of endogenous GDNF following calcitriol treatment may in part be
      responsible for these changes. The ability of calcitriol to lead to augmented DA
      release in the striatum suggests that calcitriol may be beneficial in disease
      processes involving dopaminergic dysfunction.

PMID- 22133429
TI  - The inhibitory action of exo- and endocannabinoids on [3H]GABA release are
      mediated by both CB1and CB2receptors in the mouse hippocampus.
AB  - Exogenous and endogenous cannabinoids play an important role in modulating the
      release of neurotransmitters in hippocampal excitatory and inhibitory networks,
      thus having profound effect on higher cognitive and emotional functions such as
      learning and memory. In this study we have studied the effect of cannabinoid
      agonists on the potassium depolarization-evoked [(3)H]GABA release from
      hippocampal synaptosomes in the wild-type (WT) and cannabinoid 1 receptor
      (CB(1)R)-null mutant mice. All tested cannabinoid agonists (WIN55,212-2,
      CP55,940, HU-210, 2-arachidonoyl-glycerol, 2-AG; delta-9-tetra-hydrocannabinol,
      THC) inhibited [(3)H]GABA release in WT mice with the following rank order of
      agonist potency: HU-210>CP55,490>WIN55,212-2>>2-AG>THC. By contrast, 2-AG and THC
      displayed the greatest efficacy eliciting almost complete inhibition of evoked
      [(3)H]GABA efflux, whereas the maximal inhibition obtained by HU-210, CP55,490,
      and WIN55,212-2 were less, eliciting not more than 40% inhibition. The inhibitory
      effect of WIN55,212-2, THC and 2-AG on evoked [(3)H]GABA efflux was antagonized
      by the CB(1) receptor inverse agonist AM251 (0.5 MUM) in the WT mice. In the
      CB(1)R knockout mice the inhibitory effects of all three agonists were
      attenuated. In these mice, AM251 did not antagonize, but further reduced the
      [(3)H]GABA release in the presence of the synthetic agonist WIN55,212-2. By
      contrast, the concentration-dependent inhibitory effects of THC and 2-AG were
      partially antagonized by AM251 in the absence of CB(1) receptors. Finally, the
      inhibition of evoked [(3)H]GABA efflux by THC and 2-AG was also partially
      attenuated by AM630 (1 MUM), the CB(2) receptor-selective antagonist, both in WT
      and CB(1) knockout mice. Our data prove the involvement of CB(1) receptors in the
      effect of exo- and endocannabinoids on GABA efflux from hippocampal nerve
      terminals. In addition, in the effect of the exocannabinoid THC and the
      endocannabinoid 2-AG, non-CB(1), probably CB(2)-like receptors are also involved.

PMID- 22133430
TI  - Dynamic evolution of supported metal nanocatalyst/carbon structure during single
      walled carbon nanotube growth.
AB  - Single-walled carbon nanotubes (SCWNTs) have outstanding properties that depend
      on structural features such as their chirality. Thus, developing a strategy to
      control chirality during SWCNT synthesis is critical for the exploitation of
      nanotube-based technologies in fields such as electronics and biomedicine. In
      response to this need, tuning the nanocatalyst structure has been envisioned as a
      means to control the nanotube structure. We use reactive classical molecular
      dynamics to simulate nanotube growth on supported Ni(32), Ni(80), and Ni(160)
      nanoparticles at various metal/support interaction strengths (E(adh)). The
      initial carbon ring formation is shown to correlate to the nanoparticle surface
      structure, demonstrating the existence of a "template effect" through a dominant
      occupation of hollow sites. The E(adh) strength alters the dynamic/structural
      behavior of the nanoparticle, in turn influencing the interplay between nanotube
      and nanoparticle structures. For example, the contact region between the
      nanoparticle surface and the growing nanotube decreases as E(adh) increases
      because capillary forces that raise the metal into the nanotube are counteracted
      by the strong metal/support interaction. The nanoparticle mobility decreases as
      E(adh) increases, eliminating a possible inverse template effect but hindering
      defect annealing in detriment of the nanotube/nanoparticle structural
      correlation. On the other hand, the contact between the nanoparticle and the
      nanotube increases with nanoparticle size. However, the heterogeneity of the
      nanoparticle structure increases with size, reducing the structural correlation.
      These results suggest that an appropriate combination of nanoparticle size and
      strength of the catalyst/support interaction may enhance the desired template
      effect and bias formation of specific nanotube chiralities.

PMID- 22133431
TI  - The structure and enzymatic properties of a novel RNase II family enzyme from
      Deinococcus radiodurans.
AB  - Exoribonucleases are vital in nearly all aspects of RNA metabolism, including RNA
      maturation, end-turnover, and degradation. RNase II and RNase R are paralogous
      members of the RNR superfamily of nonspecific, 3'->5', processive
      exoribonucleases. In Escherichia coli, RNase II plays a primary role in mRNA
      decay and has a preference for unstructured RNA. RNase R, in contrast, is capable
      of digesting structured RNA and plays a role in the degradation of both mRNA and
      stable RNA. Deinococcus radiodurans, a radiation-resistant bacterium, contains
      two RNR family members. The shorter of these, DrR63, includes a sequence
      signature typical of RNase R, but we show here that this enzyme is an RNase II
      type exonuclease and cannot degrade structured RNA. We also report the crystal
      structure of this protein, now termed DrII. The DrII structure reveals a
      truncated RNA binding region in which the N-terminal cold shock domains, typical
      of most RNR family nucleases, are replaced by an unusual winged helix-turn-helix
      domain, where the "wing" is contributed by the C-terminal S1 domain. Consistent
      with its truncated RNA binding region, DrII is able to remove 3' overhangs from
      RNA molecules closer to duplexes than do other RNase II-type enzymes. DrII also
      displays distinct sensitivity to pyrimidine-rich regions of single-stranded RNA
      and is able to process tRNA precursors with adenosine-rich 3' extensions in
      vitro. These data indicate that DrII is the RNase II of D. radiodurans and that
      its structure and catalytic properties are distinct from those of other related
      enzymes.

PMID- 22133432
TI  - Engineered Escherichia coli capable of co-utilization of cellobiose and xylose.
AB  - Natural ability to ferment the major sugars (glucose and xylose) of plant biomass
      is an advantageous feature of Escherichia coli in biofuel production. However,
      excess glucose completely inhibits xylose utilization in E. coli and decreases
      yield and productivity of fermentation due to sequential utilization of xylose
      after glucose. As an approach to overcome this drawback, E. coli MG1655 was
      engineered for simultaneous glucose (in the form of cellobiose) and xylose
      utilization by a combination of genetic and evolutionary engineering strategies.
      The recombinant E. coli was capable of utilizing approximately 6 g/L of
      cellobiose and 2 g/L of xylose in approximately 36 h, whereas wild-type E. coli
      was unable to utilize xylose completely in the presence of 6 g/L of glucose even
      after 75 hours. The engineered strain also co-utilized cellobiose with mannose or
      galactose; however, it was unable to metabolize cellobiose in the presence of
      arabinose and glucose. Successful cellobiose and xylose co-fermentation is a
      vital step for simultaneous saccharification and co-fermentation process and a
      promising step towards consolidated bioprocessing.

PMID- 22133433
TI  - Enhancing macrolide production in Streptomyces by coexpressing three heterologous
      genes.
AB  - Antibiotic production in Streptomyces can often be increased by introducing
      heterologous genes into strains that contain an antibiotic biosynthesis gene
      cluster. A number of genes are known to be useful for this purpose. We chose
      three such genes and cloned them singly or in combination under the control of
      the strong constitutive ermE* promoter into a phi-derived integrating vector that
      can be transferred efficiently by conjugation from Escherichia coli to
      Streptomyces. The three genes are adpA, a global regulator from Streptomyces
      coelicolor, metK, encoding S-adenosylmethionine synthetase from S. coelicolor,
      and, VHbS, hemoglobin from Vitreoscilla. The substitutions with GC in VHbS was
      intended to convert codons from lower usage to higher, yet causing no change to
      the encoded amino acid. Plasmids containing either one of these genes or genes in
      various combinations were introduced into Streptomyces sp. FR-008, which produces
      the macrolide antibiotic FR-008-III (also known as candicidin D). The largest
      increase in FR-008-III production was achieved by the plasmid containing all
      three genes. This plasmid also increased avermectin production in Streptomyces
      avermitilis, and is likely to be generally useful for improving antibiotic
      production in Streptomyces.

PMID- 22133434
TI  - Nano reengineering of horseradish peroxidase with dendritic macromolecules for
      stability enhancement.
AB  - A simple bio-conjugation procedure to surround a single horseradish peroxidase
      (HRP) enzyme molecule with dendritic polyester macromolecules (polyester-32
      hydroxyl-1-carboxyl bis-MPA dendron, generation 5) was proposed. The
      characterization of resultant nanoparticles entitled HRP dendrozyme, was
      performed by transmission electron microscopy, dynamic light scattering, gel
      permeation chromatography and Fourier transform infrared spectroscopy. The
      results showed that HRP nanoparticles were spherical in shape and have an average
      size of 14+/-2 nm in diameter. Furthermore, bio-conformational characterization
      of HRP dendrozyme was performed by means of circular dichroism and fluorescence
      spectroscopy to evaluate the secondary and tertiary structure changes after
      enzyme modification. These investigations revealed that protein conformation had
      small changes (in secondary and tertiary structures) after bio-conjugation. We
      also reported here that dendritic modification did not significantly affect the
      kinetic parameters of free HRP. The stabilization of HRP with dendron
      macromolecules as single enzyme nanoparticles resulted in improvement of half
      life over 70 days storage at 4  degrees C as well as its tolerance under
      different elevated temperatures up to 80  degrees C and in the presence of
      organic solvents for 15 min. These significant results promise extensive
      applications of HRP particularly in harsh environmental conditions.

PMID- 22133435
TI  - Cloning and functional expression of the mitochondrial alternative oxidase gene
      (aox1) of Aspergillus niger in Lactococcus lactis and its induction by oxidizing
      conditions.
AB  - Lactococcus lactis is a widely used food bacterium mainly known for its
      fermentation metabolism. An important, and for long time overlooked, trait of
      this species is its ability to perform respiratory metabolism in the presence of
      heme and under aerobic conditions. There is no evidence however for the presence
      of an alternative respiration pathway and AOX activity. In this study, a cDNA
      fragment encoding the mitochondrial alternative oxidase, the enzyme responsible
      for alternative respiration, from a citric acid producing Aspergillus niger
      strain was cloned and expressed in L. lactis as a host strain. Expression of aox1
      conferred on this organism cyanide-resistant and salicylhydroxamate-sensitive
      growth. Bioreactor cultures under fully aerobic conditions of the transformed L.
      lactis showed that the alternative respiratory pathway operates and improves
      significantly the microorganism's response to oxidizing stress conditions as it
      enhances biomass production, suppresses lactate formation, and leads to
      accumulation of large amounts of nisin.

PMID- 22133436
TI  - Intracellular expression of Vitreoscilla hemoglobin improves production of
      Yarrowia lipolytica lipase LIP2 in a recombinant Pichia pastoris.
AB  - The Yarrowia lipolytica lipase LIP2 (YlLIP2) gene lip2 and Vitreoscilla
      hemoglobin gene vgb were co-expressed in Pichia pastoris, both under the control
      of AOX1 promoter, in order to alleviate respiration limitation under conditions
      of high cell-density fermentation and enhance YlLIP2 production. The results
      showed that recombinant P. pastoris strains harboring the lip2 and vgb genes
      (VHb(+)) displayed higher biomass and YlLIP2 activity than control strains (VHb(
      )). Compared with VHb(-) cells, the expression levels of YlLIP2 in VHb-expressing
      cells when oxygen was not a limiting factor were improved 31.5% in shake-flask
      culture and 22% in a 10-L fermentor. Under non-limiting dissolved oxygen (DO)
      conditions, the maximum YlLIP2 activity of VHb(+) in a 10-L fermentor reached
      33,000 U/mL. Oxygen limitation had a more negative effect on YlLIP2 productivity
      in VHb(-) cells than in VHb(+) cells. The highest YlLIP2 activity of VHb(+) cells
      was approximately 1.84-fold higher than that of VHb(-) cells at lower DO levels.
      Moreover, the recombinant strain VHb(+) exhibited a higher specific oxygen uptake
      rate and achieved higher cell viability under oxygen limiting and non-limiting
      conditions compared with VHb(-) cells. Therefore, the above results suggest that
      intracellular expression of VHb in recombinant P. pastoris has the potential to
      improve cell growth and industrial enzyme production.

PMID- 22133437
TI  - Enhanced anthocyanins and resveratrol production in Vitis vinifera cell
      suspension culture by indanoyl-isoleucine, N-linolenoyl-L-glutamine and insect
      saliva.
AB  - The effects of two synthetic elicitor indanoyl-isoleucine (In-Ile), N-linolenoyl
      L-glutamine (Lin-Gln) and one biotic elicitor insect saliva (from Manduca sexta
      larvae) on plant cell cultures with respect to the induction of secondary
      metabolite production were investigated. Stimulated production of secondary
      metabolites, particularly anthocyanins in plant cells and phenolic acids in
      culture medium, was studied by using suspension culture of Vitis vinifera L. cv.
      Gamay Freaux as a model system. In the treatments with In-Ile, the production of
      anthocyanins was enhanced 2.6-fold. In-Ile, Lin-Gln and saliva significantly
      elevated the accumulation of phenolic acids, particularly 3-O-glucosyl
      resveratrol. The used elicitors did not suppress cell growth. Secondary
      metabolites were differently responsive to elicitation. 3-O-glucosyl-resveratrol
      was the predominant phenolic acid in V. vinifera cell culture, and its production
      was significantly stimulated by saliva, with 7.0-fold of the control level 24 h
      after treatment. The production of 4-(3,5-dihydroxy-phenyl)-phenol was
      significantly stimulated by In-Ile with 6.4-fold of the control level 24 h after
      treatment.

PMID- 22133438
TI  - An innovative biocatalyst for production of ethanol from xylose in a continuous
      bioreactor.
AB  - The use of the hemicellulose fraction of biomass may be important for the
      feasibility of the production of second generation bioethanol. Wild strains of
      Saccharomyces cerevisiae are widely used in industry for production of 1st
      generation ethanol, and the robustness of this yeast is an important advantage in
      large scale applications. Isomerization of xylose to xylulose is an essential
      step in this process. This reaction is catalyzed by glucose isomerase (GI). A new
      biocatalyst is presented here for the simultaneous isomerization and fermentation
      (SIF) of xylose. GI from Streptomyces rubiginosus was immobilized in chitosan,
      through crosslinking with glutaraldehyde, and the support containing the
      immobilized GI (IGI-Ch) was co-immobilized with S. cerevisiae, in calcium
      alginate gel. The immobilization experiments led to high immobilized protein
      loads (30-68 mg * g(support)(-1)), high yields (circa of 100%) and high recovered
      enzyme activity (>90%). The IGI-Ch derivative with maximum activity presented
      1700 IU * g(catalyst)(-1), almost twice the activity of a commercial immobilized
      GI, GENSWEET((r)) IGI-HF. At typical operational conditions for xylose SIF
      operation (pH 5, 30-35  degrees C, presence of nutrients and ethanol
      concentrations in the medium up to 70 L(-1)), both derivatives, IGI-Ch and
      GENSWEET((r)) IGI-HF retained app. 90% of the initial activity after 120 h, while
      soluble GI was almost completely inactive at pH 5, 30  degrees C. The
      isomerization xylose/xylulose, catalyzed by IGI-Ch, reached the equilibrium in
      batch experiments after 4h, with 12,000 IU * L(-1) (7 g(der) * L(-1)), at pH 5
      and 30  degrees C, in the presence of fermentation nutrients. After co
      immobilization of IGI-Ch with yeast in alginate gel, this biocatalyst succeeded
      in producing 12 g * L(-1) of ethanol, 9.5 g * L(-1) of xylitol, 2.5 g * L(-1) of
      glycerol and 1.9 g * L(-1) of acetate after consumption of 50 g * L(-1) of
      xylose, in 48 h, using 32.5 * 10(3) IU * L(-1) and 20 g(yeast) * L(-1), at 35 
      degrees C and initial pH 5.3.

PMID- 22133439
TI  - Improvement of the biocatalytic properties of one phenylacetone monooxygenase
      mutant in hydrophilic organic solvents.
AB  - The presence of different hydrophilic organic solvents or a water soluble polymer
      such as PEG 4000 led to an enhancement in the enzymatic activity of the M446G
      mutant of phenylacetone monooxygenase when it is employed in enantioselective
      sulfoxidations and Baeyer-Villiger reactions. By solvent engineering new
      substrates were found to be effectively converted by this Baeyer-Villiger
      monooxygenase. The use of 5% methanol together with the weak anion exchange resin
      Lewatit MP62 also allows the dynamic kinetic resolution of a set of racemic
      benzylketones. By this approach (S)-benzylesters could be obtained with high
      yields and optical purities.

PMID- 22133440
TI  - Glucosylation of the flavonoid, astragalin by Leuconostoc mesenteroides B-512FMCM
      dextransucrase acceptor reactions and characterization of the products.
AB  - Astragalin (kaempferol-3-O-beta-D-glucopyranoside, Ast) glucosides were
      synthesized by the acceptor reaction of a dextransucrase produced by Leuconostoc
      mesenteroides B-512FMCM with astragalin and sucrose. Each glucoside was purified
      and their structures were assigned as kaempferol-3-O-beta-D-glucopyranosyl-(1->3)
      O-alpha-D-glucopyranoside (or kaempferol-3-O-beta-D-nigeroside, Ast-G1') and
      kaempferol-3-O-beta-D-glucopyranosyl-(1->6)-O-alpha-D-glucopyranoside (or
      kaempferol-3-O-beta-D-isomaltoside, Ast-G1) for one glucose transferred, and
      kaempferol-3-O-beta-D-isomaltooligosacharide (Ast-IMO or Ast-Gn; n=2-8). The
      astragalin glucosides exhibited 8.3-60.6% higher inhibitory effects on matrix
      metalloproteinase-1 expression, 18.8-20.3% increased antioxidant effects, and 3.8
      18.8% increased inhibition activity of melanin synthesis compared to control
      (without the addition of compound), depending on the number of glucosyl residues
      linked to astragalin. These novel compounds could be used to further expand the
      industrial applications of astragalin glucosides, in particular in the cosmetics
      industry.

PMID- 22133441
TI  - Microbial sucrose isomerases: producing organisms, genes and enzymes.
AB  - Sucrose isomerase (SI) activity is used industrially for the conversion of
      sucrose into isomers, particularly isomaltulose or trehalulose, which have
      properties advantageous over sucrose for some food uses. All of the known
      microbial SIs are TIM barrel proteins that convert sucrose without need for any
      cofactors, with varying kinetics and product specificities. The current analysis
      was undertaken to bridge key gaps between the information in patents and
      scientific publications about the microbes and enzymes useful for sucrose isomer
      production. This analysis shows that microbial SIs can be considered in 5
      structural classes with corresponding functional distinctions that broadly align
      with the taxonomic differences between producing organisms. The most widely used
      bacterial strain for industrial production of isomaltulose, widely referred to as
      "Protaminobacter rubrum" CBS 574.77, is identified as Serratia plymuthica. The
      strain producing the most structurally divergent SI, with a high product
      specificity for trehalulose, widely referred to as "Pseudomonas mesoacidophila"
      MX-45, is identified as Rhizobium sp. Each tested SI-producer is shown to have a
      single SI gene and enzyme, so the properties reported previously for the isolated
      proteins can reasonably be associated with the products of the genes subsequently
      cloned from the same isolates and SI classes. Some natural isolates with potent
      SI activity do not catabolize the isomer under usual production conditions. The
      results indicate that their industrial potential may be further enhanced by
      selection for variants that do not catabolize the sucrose substrate.

PMID- 22133442
TI  - Recovery of active N-acetyl-D-glucosamine 2-epimerase from inclusion bodies by
      solubilization with non-denaturing buffers.
AB  - Overexpression of recombinant N-acetyl-D-glucosamine 2-epimerase, one of the key
      enzymes for the synthesis of N-acetylneuraminic acid, in E. coli led to the
      formation of protein inclusion bodies. In this study we report the recovery of
      active epimerase from inclusion bodies by direct solubilization with Tris buffer.
      At pH 7.0, 25% of the inclusion bodies were solubilized with Tris buffer. The
      specific activity of the solubilized proteins, 2.08+/-0.02 U/mg, was similar to
      that of the native protein, 2.13+/-0.01 U/mg. The result of circular dichroism
      spectroscopy analysis indicated that the structure of the solubilized epimerase
      obtained with pH 7.0 Tris buffer was similar to that of the native epimerase
      purified from the clarified cell lysate. As expected, the extent of deviation in
      CD spectra increased with buffer pH. The total enzyme activity recovered by
      solubilization from inclusion bodies, 170.41+/-10.06 U/l, was more than 2.5 times
      higher than that from the clarified cell lysate, 67.32+/-5.53 U/l. The results
      reported in this study confirm the hypothesis that the aggregation of proteins
      into inclusion bodies is reversible and suggest that direct solubilization with
      non-denaturing buffers is a promising approach for the recovery of active
      proteins from inclusion bodies, especially for aggregation-prone multisubunit
      proteins.

PMID- 22133443
TI  - Production of L-xylose from L-xylulose using Escherichia coli L-fucose isomerase.
AB  - L-Xylulose was used as a raw material for the production of L-xylose with a
      recombinantly produced Escherichia coli L-fucose isomerase as the catalyst. The
      enzyme had a very alkaline pH optimum (over 10.5) and displayed Michaelis-Menten
      kinetics for L-xylulose with a K(m) of 41 mM and a V(max) of 0.23 MUmol/(mg min).
      The half-lives determined for the enzyme at 35  degrees C and at 45  degrees C
      were 6h 50 min and 1h 31 min, respectively. The reaction equilibrium between L
      xylulose and L-xylose was 15:85 at 35  degrees C and thus favored the formation
      of L-xylose. Contrary to the L-rhamnose isomerase catalyzed reaction described
      previously [14]L-lyxose was not detected in the reaction mixture with L-fucose
      isomerase. Although xylitol acted as an inhibitor of the reaction, even at a high
      ratio of xylitol to L-xylulose the inhibition did not reach 50%.

PMID- 22133444
TI  - The ferulic acid esterases of Chrysosporium lucknowense C1: purification,
      characterization and their potential application in biorefinery.
AB  - Three ferulic acid esterases from the filamentous fungus Chrysosporium
      lucknowense C1 were purified and characterized. The enzymes were most active at
      neutral pH and temperatures up to 45  degrees C. All enzymes released ferulic
      acid and p-coumaric acid from a soluble corn fibre fraction. Ferulic acid
      esterases FaeA1 and FaeA2 could also release complex dehydrodiferulic acids and
      dehydrotriferulic acids from corn fibre oligomers, but released only 20% of all
      ferulic acid present in sugar beet pectin oligomers. Ferulic acid esterase FaeB2
      released almost no complex ferulic acid oligomers from corn fibre oligomers, but
      60% of all ferulic acid from sugar beet pectin oligomers. The ferulic acid
      esterases were classified based on both, sequence similarity and their activities
      toward synthetic substrates. The type A ferulic acid esterases FaeA1 and FaeA2
      are the first members of the phylogenetic subfamily 5 to be biochemically
      characterized. Type B ferulic acid esterase FaeB2 is a member of subfamily 6.

PMID- 22133445
TI  - Cortical bone is more sensitive to alcohol dose effects than trabecular bone in
      the rat.
AB  - OBJECTIVE: While chronic alcohol consumption is known to decrease bone mineral
      content (BMC), bone mineral density (BMD), and negatively modify trabecular bone
      microarchitecture, the impact of alcohol on cortical microarchitecture is still
      unclear. The aim of this study was to investigate the effects of various doses of
      alcohol on bone density, trabecular and cortical parameters and bone strength in
      rats. METHODS: Forty-eight male Wistar rats were divided into four groups:
      control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v
      (A35). Rats in the alcohol groups were fed a solution composed of ethanol and
      water for 17 weeks while the control group drank only water. Bone quality and
      quantity were evaluated through the analysis of density, trabecular and cortical
      bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations
      and a 3-point bending test. RESULTS: Bone density along with trabecular and
      cortical thickness were lower in alcohol groups compared to C. BMD was lower in
      A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number
      was increased by alcohol and the porosity was greater in A35 compared to C. N
      Telopeptide concentration was decreased in alcohol groups compared to control
      whereas no differences were observed in osteocalcin concentrations. Maximal
      energy to failure was lower in A25 and A35 compared to C. CONCLUSION: Chronic
      ethanol consumption increases cortical bone damage in rats and may have
      detrimental effects on bone strength. These effects were dose-dependent, with
      greater negative effects proportionate to greater alcohol doses.

PMID- 22133446
TI  - Nickel ENMs activate HIF-1alpha.

PMID- 22133447
TI  - Opioid-free single-incision laparoscopic (SIL) cholecystectomy using bilateral
      TAP blocks.
AB  - A 30 year old woman who was 8 weeks postpartum with a history of cholelithiasis
      and gallstone pancreatitis, and who was status-post endoscopic retrograde
      cholangiopancreatography (ERCP) with sphincterotomy, was treated with a single
      incision laparoscopic (SIL) cholecystectomy. A transversus abdominis plane block
      (TAP) was performed after induction of anesthesia. The patient required no
      intraoperative or postoperative opioids.

PMID- 22133448
TI  - Safe surgery: how accurate are we at predicting intra-operative blood loss?
AB  - INTRODUCTION: Preoperative estimation of intra-operative blood loss by both
      anaesthetist and operating surgeon is a criterion of the World Health
      Organization's surgical safety checklist. The checklist requires specific
      preoperative planning when anticipated blood loss is greater than 500 mL. The aim
      of this study was to assess the accuracy of surgeons and anaesthetists at
      predicting intra-operative blood loss. METHODS: A 6-week prospective study of
      intermediate and major operations in an academic medical centre was performed. An
      independent observer interviewed surgical and anaesthetic consultants and
      registrars, preoperatively asking each to predict expected blood loss in
      millilitre. Intra-operative blood loss was measured and compared with these
      predictions. Parameters including the use of anticoagulation and anti-platelet
      therapy as well as intra-operative hypothermia and hypotension were recorded.
      RESULTS: One hundred sixty-eight operations were included in the study, including
      142 elective and 26 emergency operations. Blood loss was predicted to within 500
      mL of measured blood loss in 89% of cases. Consultant surgeons tended to
      underestimate blood loss, doing so in 43% of all cases, while consultant
      anaesthetists were more likely to overestimate (60% of all operations). Twelve
      patients (7%) had underestimation of blood loss of more than 500 mL by both
      surgeon and anaesthetist. Thirty per cent (n = 6/20) of patients requiring
      transfusion of a blood product within 24 hours of surgery had blood loss
      underestimated by more than 500 mL by both surgeon and anaesthetist. There was no
      significant difference in prediction between patients on anti-platelet or
      anticoagulation therapy preoperatively and those not on the said therapies.
      CONCLUSION: Predicted intra-operative blood loss was within 500 mL of measured
      blood loss in 89% of operations. In 30% of patients who ultimately receive a
      blood transfusion, both the surgeon and anaesthetist significantly underestimate
      the risk of blood loss by greater than 500 mL. Theatre staff must be aware that 1
      in 14 patients undergoing intermediate or major surgery will have an unexpected
      blood loss exceeding 500 mL and so robust policies to identify and manage such
      circumstances should be in place to improve patient safety.

PMID- 22133449
TI  - Polymorphisms of the promoter and exon 3 of the receptor for advanced glycation
      end products (RAGE) in Euro- and Afro-Brazilians.
AB  - The receptor for advanced glycation end products (RAGE or AGER), a member of the
      immunoglobulin superfamily, is involved in pathologies such as atherosclerosis
      and diabetes. Over 50 SNPs were reported for RAGE, among which were the promoter
      region polymorphisms -429T>C (rs1800625), -374T>A (rs1800624) and a 63-bp
      deletion (-407 to -345 bp), all related to increased RAGE expression.
      Additionally, in the exon 3, a putative site of binding ligands, the missense
      variation G82S (rs2070600) was associated with skin disorders in patients with
      diabetes. We have determined allele, genotype and haplotype frequencies of RAGE
      polymorphisms -429T>C, -374T>A, 63-bp deletion and G82S in Euro-Brazilians (n =
      108) and Afro-Brazilians (n = 91), characterized according to the predominant
      ancestry of the individuals. The allele frequencies for Euro- and Afro-Brazilians
      were as follows: -429C, 12.5% vs. 12.1% (P = 0.90); -374A, 31.5% vs. 26.2% (P =
      0.25); 63del, 0.0% vs. 3.8% (P = 0.004); and 82S, 1.9% vs. 0.6% (P = 0.24).
      Absolute linkage disequilibrium was found between the promoter polymorphisms 
      429T>C and -374T>A plus the 63-bp deletion (D'=1.000; P < 0.0001). The haplotype
      frequencies differed (P = 0.003) between Euro- and Afro-Brazilians. Our results
      showed that the frequencies of the 63-bp deletion were higher in Afro-Brazilians,
      while the other analysed polymorphisms were similarly distributed in the studied
      populations. The -374T>A plus 63-bp deletion polymorphism captures more than 80%
      of the haplotypic variation in the studied population.

PMID- 22133450
TI  - A randomized controlled evaluation of an online chronic pain self management
      program.
AB  - Internet-based educational and therapeutic programs (e-health applications) are
      becoming increasingly popular for a variety of psychological and physical
      disorders. We tested the efficacy of an online Chronic Pain Management Program, a
      comprehensive, fully self-directed and self-paced system that integrates social
      networking features and self-management tools into an interactive learning
      environment. Of 305 adult participants (196 women, 109 men), a total of 162
      individuals with chronic pain were randomly assigned unsupervised access to the
      program for approximately 6 weeks; 143 were assigned to the wait-listed control
      group with treatment as usual. A comprehensive assessment was administered before
      the study and approximately 7 and 14 weeks thereafter. All recruitment, data
      collection, and participant involvement took place online. Participation was
      fully self-paced, permitting the evaluation of program effectiveness under real
      world conditions. Intent-to-treat analysis that used linear growth models was
      used as the primary analytic tool. Results indicated that program utilization was
      associated with significant decreases in pain severity, pain-related interference
      and emotional burden, perceived disability, catastrophizing, and pain-induced
      fear. Further, program use led to significant declines in depression, anxiety,
      and stress. Finally, as compared to the wait-listed control group, the
      experimental group displayed a significant increase in knowledge about the
      principles of chronic pain and its management. Study limitations are considered,
      including the recognition that not all persons with chronic pain are necessarily
      good candidates for self-initiated, self-paced, interactive learning.

PMID- 22133451
TI  - Intramuscular metastasis of malignant melanoma mimicking leg cellulitis.

PMID- 22133452
TI  - The impact of ablation of incompetent superficial and perforator veins on ulcer
      healing rates.
AB  - OBJECTIVE: We assessed the impact of endovenous ablation of incompetent
      superficial (great saphenous [GSV] and small saphenous [SSV]) and perforator
      (posterior tibial [PTPV]) veins on the healing rate of venous ulcers in patients
      who had failed conventional compression therapy. METHODS: Patients with CEAP 6
      ulcers were treated with weekly compression in a dedicated wound care center.
      Ulcer size and depth were tracked prospectively. Those ulcers that showed no
      measurable improvement after >5 weeks of compression therapy underwent ablation
      of at least one incompetent vein. RESULTS: We performed 140 consecutive
      endovenous ablation procedures (74 superficial and 66 perforator) on 110 venous
      ulcers in 88 limbs. Ulcers had been present for 71 +/- 6 months with an initial
      ulcer area of 23 +/- 6 cm(2). Following successful ablation, the healing rate for
      healed ulcers improved from + 1.0 +/- .1 cm(2)/month to -4.4 +/- .1 cm(2)/month
      (P > .05). Ulcer healing rate for healed ulcers, based on the last vein ablated,
      was GSV = 6.4 cm(2)/month, SSV = 4.8 cm(2)/month, and PTPV = 2.9 cm(2)/month.
      After a minimum observation period of 6 months (mean follow up, 12 +/- 1.25
      months), 76.3% of patients healed in 142 +/- 14 days. Twelve patients with 26
      ulcers did not heal: two patients died from unrelated illnesses, six patients are
      still actively healing, and four patients have been lost to follow up. Of the
      healed ulcers, four patients with six ulcers (7.1%) recurred; two have rehealed.
      CONCLUSION: There is measurable and significant reduction in ulcer size and
      ultimate healing following ablation of incompetent superficial and perforator
      veins in patients who have failed conventional compression therapy.

PMID- 22133453
TI  - Ischemic preconditioning ameliorates spinal cord ischemia-reperfusion injury by
      triggering autoregulation.
AB  - OBJECTIVE: The mechanism underlying ischemic preconditioning (IPC) protection
      against spinal cord ischemia-reperfusion (I/R) injury is unclear. We investigated
      the role of spinal cord autoregulation in tolerance to spinal cord I/R injury
      induced by IPC in a rat model. METHODS: Sprague-Dawley rats were randomly
      assigned to four groups. IPC (P) group animals received IPC by temporary thoracic
      aortic occlusion (AO) with a 2F Fogarty arterial embolectomy catheter (Baxter
      Healthcare, Irvine, Calif) for 3 minutes. The I/R injury (I/R) group animals were
      treated with blood withdrawal and temporary AO for 12 minutes, and shed blood
      reinfusion at the end of the procedures. The P+I/R animals received IPC, followed
      by 5 minutes reperfusion, and then I/R procedures for 12 minutes. Sham (S) group
      animals received anesthesia and underwent surgical preparation, but without
      preconditioning or I/R injury. Neurologic function on postprocedure days 1, 3, 5,
      and 7 was evaluated by Tarlov scoring. Lumbar segments were harvested for
      histopathologic examination on day 7. To evaluate the role of autoregulation in
      IPC, spinal cord blood flow and tissue oxygenation were continuously monitored
      throughout the procedure duration. RESULTS: The Tarlov scores in the I/R group
      were significantly lower than those in the S, P, and P+I/R groups on days 1, 3,
      5, and 7 (P < .001). No significant differences were noted between the S, P, and
      P+I/R groups. The numbers of surviving motor neurons in the S, P, and P+I/R
      groups were significantly higher than those in the I/R group (P < .001); however,
      the number of surviving motor neurons did not differ between the S, P, and P+I/R
      groups. The P group exhibited higher spinal cord blood flow (P = .001-.043) and
      tissue oxygenation (P = .032-.043) within the first 60 minutes after reperfusion
      than the S group. The P+I/R group exhibited higher spinal cord blood flow (P =
      .016-.045) and tissue oxygenation (P = .001-.038) within the first 60 minutes
      after reperfusion than the I/R group. CONCLUSIONS: IPC ameliorates spinal cord
      I/R injury in rats, probably mediated by triggering spinal cord autoregulation
      and improving local spinal cord blood flow and tissue oxygenation. This concept
      may be the new therapeutic targets in patients requiring aortic surgery.

PMID- 22133454
TI  - Evidence for nonoperative management of acute limb ischemia in infants.
AB  - Acute limb ischemia (ALI) in infants is a catastrophic event. We performed a
      query of our database to determine those with ALI. Twelve patients were
      identified. The most frequent presentation was cyanotic limbs. Eleven patients
      were treated nonoperatively with anticoagulation. One patient was treated
      surgically with Fogarty balloon thrombectomy. There were three deaths all due to
      associated comorbidities. All had viable limbs on follow-up examination. There
      were three complications in the patients managed conservatively. Our
      recommendation for infants presenting with ALI is conservative observation with
      anticoagulation and intervention only for cases with tissue loss.

PMID- 22133456
TI  - Assessing outcomes to determine whether symptoms related to hypertension justify
      renal artery stenting.
AB  - OBJECTIVE: The goal of the study was to determine the blood pressure (BP)
      response to renal artery stenting (RAS) for patients with hypertension urgency,
      hypertension emergency, and angina with congestive heart failure
      (angina/congestive heart failure [CHF]). METHODS: Patients who underwent RAS for
      hypertension emergencies (n = 13), hypertension urgencies (n = 25), and
      angina/CHF (n = 14) were included in the analysis. By convention, hypertension
      urgency was defined by a sustained systolic BP >= 180 mm Hg or diastolic BP >=
      120 mm Hg, while the definition of hypertension emergency required the same BP
      parameters plus hypertension-related symptoms prompting hospitalization. Patient
      specific response to RAS was defined according to modified American Heart
      Association reporting guidelines. RESULTS: The study cohort of 52 patients had a
      median age of 66 years (interquartile range 58-72). The BP response to RAS varied
      significantly according to the indication for RAS. Hypertension emergency
      provided the highest BP response rate (85%), while the response rate was
      significantly lower for hypertension urgency (52%) and angina/CHF (7%; P = .03).
      Only 1 of 14 patients with angina/CHF was a BP responder. Multivariate analysis
      showed that hypertension urgency or emergency were not independent predictors of
      BP response to RAS. Instead, the only independent predictor of a favorable BP
      response was the number of preoperative antihypertensive medications (odds ratio
      7.5; 95% confidence interval 2.5-22.9; P = .0004), which is another indicator of
      the severity of hypertension. Angina/CHF was an independent predictor of failure
      to respond to RAS (odds ratio 118.6; 95% confidence interval 2.8-999.9; P =
      .013). CONCLUSIONS: Hypertension urgency and emergency are clinical
      manifestations of severe hypertension, but the number of preoperative
      antihypertensive medications proved to be a better predictor of a favorable BP
      response to RAS. In contrast, angina/CHF was a predictor of failure to respond to
      stenting, providing further evidence against the practice of incidental stenting
      during coronary interventions.

PMID- 22133458
TI  - Isoxazoles incorporated N-substituted decahydroquinolines: a precursor to the
      next generation antimicrobial drug.
AB  - We report here a simple entry into N-substituted decahydroisoxazoloquinoline
      system with substituents at position 3 and 4 from the readily available
      substrates for the first time. The synthesized isoxazoloquinolines were evaluated
      against six bacterial and four fungal strains. The results suggest that the
      decahydroisoxazolo[4,3-c]quinoline scaffold has the potential to be developed
      into therapeutically useful antimicrobial agents.

PMID- 22133459
TI  - New potent 5-HT(2A) receptor ligands containing an N'-cyanopicolinamidine
      nucleus: Synthesis and in vitro pharmacological evaluation.
AB  - N'-cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were
      prepared and their affinity to serotonin 5-HT(1A), 5-HT(2A) and 5-HT(2C)
      receptors were evaluated. The combination of structural elements (heterocyclic
      nucleus, alkyl chain and 4-substituted piperazine) known to be critical for
      affinity to 5-HT(1A) receptors and the proper selection of substituents led to
      compounds with high specificity and affinity towards serotoninergic receptors. In
      binding studies, several molecules showed affinity in nanomolar and subnanomolar
      range at 5-HT(2A) and moderate to no affinity for other relevant receptors (5
      HT(1A), 5-HT(2C), D(1), D(2), alpha(1) and alpha(2)). N'-cyano-N-(3-(4-(3
      chlorophenyl)piperazin-1-yl)propyl)-picolinamidine (4l) with K(i)=0.000185nM, was
      the most active and selective derivative for the 5-HT(2A) receptor compared to
      other serotoninergic, dopaminergic and adrenergic receptors.

PMID- 22133461
TI  - Risk or resilience? Empathic abilities in patients with bipolar disorders and
      their first-degree relatives.
AB  - Endophenotypes are intermediate phenotypes which are considered a more promising
      marker of genetic risk than illness itself. While previous research mostly used
      cognitive deficits, emotional functions are of greater relevance for bipolar
      disorder regarding the characteristic emotional hyper-reactability and deficient
      social-emotional competence. Hence, the aim of the present study was to clarify
      whether empathic abilities can serve as a possible endophenotype of bipolar
      disorder by applying a newly developed task in bipolar patients and their first
      degree relatives. Three components of empathy (emotion recognition, perspective
      taking and affective responsiveness) have been assessed in a sample of 21 bipolar
      patients, 21 first-degree relatives and 21 healthy controls. Data analysis
      indicated significant differences between controls and patients for emotion
      recognition and affective responsiveness but not for perspective taking. This
      shows that in addition to difficulties in recognizing facial emotional
      expressions, bipolar patients have difficulties in identifying emotions they
      would experience in a given situation. However, the ability to take the
      perspective of another person in an emotional situation was intact but decreased
      with increasing severity of residual hypomanic and depressive symptoms. Relatives
      performed comparably bad on emotion recognition but did not differ from controls
      or patients in affective responsiveness. This study is the first to show that
      deficient emotion recognition is the only component of empathy which forms a
      possible endophenotype of bipolar disorder. This has important implications for
      prevention strategies. Furthermore, changes in affective responsiveness in first
      degree relatives show a potential resilience marker.

PMID- 22133462
TI  - Perception and practice of Kangaroo Mother Care after discharge from hospital in
      Kumasi, Ghana: a longitudinal study.
AB  - BACKGROUND: The practice of Kangaroo Mother Care (KMC) is life saving in babies
      weighing less than 2000 g. Little is known about mothers' continued unsupervised
      practice after discharge from hospitals. This study aimed to evaluate its in
      hospital and continued practice in the community among mothers of low birth
      weight (LBW) infants discharged from two hospitals in Kumasi, Ghana. METHODS: A
      longitudinal study of 202 mothers and their inpatient LBW neonates was conducted
      from November 2009 to May 2010. Mothers were interviewed at recruitment to
      ascertain their knowledge of KMC, and then oriented on its practice. After
      discharge, the mothers reported at weekly intervals for four follow up visits
      where data about their perceptions, attitudes and practices of KMC were recorded.
      A repeated measure logistic regression analysis was done to assess variability in
      the binary responses at the various reviews visits. RESULTS: At recruitment 23
      (11.4%, 95%CI: 7.4 to 16.6%) mothers knew about KMC. At discharge 95.5% were
      willing to continue KMC at home with 93.1% willing to practice at night. 95.5%
      thought KMC was beneficial to them and 96.0% beneficial to their babies. 98.0%
      would recommend KMC to other mothers with 71.8% willing to practice KMC
      outdoors.At first follow up visit 99.5% (181) were still practicing either
      intermittent or continuous KMC. This proportion did not change significantly over
      the four weeks (OR: 1.4, 95%CI: 0.6 to 3.3, p-value: 0.333). Over the four weeks,
      increasingly more mothers practiced KMC at night (OR: 1.7, 95%CI: 1.2 to 2.6, p =
      0.005), outside their homes (OR: 2.4, 95%CI: 1.7 to 3.3, p < 0.001) and received
      spousal help (OR: 1.6, 95%CI: 1.1 to 2.4, p = 0.007). Household chores and
      potentially negative community perceptions of KMC did not affect its practice
      with odds of 0.8 (95%CI: 0.5 to 1.2, p = 0.282) and 1.0 (95%CI: 0.6 to 1.7, p =
      0.934) respectively. During the follow-up period the neonates gained 23.7 sg
      (95%CI: 22.6 g to 24.7 g) per day. CONCLUSION: Maternal knowledge of KMC was low
      at outset. Once initiated mothers continued practicing KMC in hospital and at
      home with their infants gaining optimal weight. Continued KMC practice was not
      affected by perceived community attitudes.

PMID- 22133463
TI  - Appy christmas.

PMID- 22133464
TI  - Decreased scale-specific heart rate variability after multiresolution wavelet
      analysis predicts sudden cardiac death in heart failure patients.

PMID- 22133465
TI  - Survival in patients with myocardial infarction complicated by out-of-hospital
      cardiac arrest undergoing emergency percutaneous coronary intervention.
AB  - OBJECTIVES: We sought to evaluate the clinical outcomes of patients with
      myocardial infarction (MI) complicated by out-of-hospital cardiac arrest (OHCA)
      undergoing percutaneous coronary intervention (PCI). BACKGROUND: Controversy
      remains regarding the benefit of early PCI in patients with MI complicated by
      OHCA. METHODS: We analyzed the outcomes of 88 consecutive patients presenting
      with MI complicated by OHCA compared to 5101 patients with MI without OHCA who
      underwent PCI from the Melbourne Interventional Group registry between 2004 and
      2009. RESULTS: Patients with OHCA had a higher proportion of ST-elevation MI
      presentations (90.9% vs. 50%, p<0.01) and were more likely to be to be in
      cardiogenic shock (38.6% vs. 4.6%, p<0.01). Procedural success was similar in the
      two groups (95.5% OHCA vs. 96.5% non-OHCA MI cohort, p=0.65). In-hospital, 30
      day, and 1-year survival in the OHCA cohort versus the non-OHCA MI cohort were
      62.5% vs. 97.2% (p<0.01), 61.4% vs. 96.5% (p<0.01), and 60.2% vs. 94.2% (p<0.01),
      respectively. Within the OHCA cohort, presentation with cardiogenic shock (OR
      7.2, 95% CI: 2.7-18.8; p<0.01) was strongly associated with in-hospital
      mortality. Importantly, 1-year survival of patients discharged alive from
      hospital was similar between the two groups (96% vs. 97% p=0.8). CONCLUSION:
      Patients with MI complicated by OHCA remain a high-risk group associated with
      high mortality. However, high procedural success rates similar to non-OHCA
      patients can be attained. Survival rates better than previously reported were
      observed with an emergent PCI approach, with 1-year survival comparable to a non
      OHCA cohort if patients survive to hospital discharge.

PMID- 22133466
TI  - Trans-telephonic ICD alert due to recommended replacement time notification: what
      is the problem?

PMID- 22133467
TI  - What is the acceptable rate of false positives for STEMI within a primary PCI
      network? Insights from a metropolitan system with direct ambulance-based access.

PMID- 22133468
TI  - Coronary microfistulae associated with non compacted myocardium: a rare cause of
      myocardial ischemia unraveled by a multimodality imaging approach.

PMID- 22133469
TI  - Impact of long-term Xuezhikang therapy on cardiovascular events in high-risk
      patients with nonspecific, preexisting abnormal liver tests: a post-hoc analysis
      from Chinese Coronary Secondary Prevention Study (CCSPS).

PMID- 22133471
TI  - Robert Tigerstedt and the discovery of renin - a revisit.

PMID- 22133470
TI  - Is target dose the treatment target? Uptitrating beta-blockers for heart failure
      in the elderly.
AB  - BACKGROUND: Guideline-recommended beta-blocker (BB) target doses for patients
      with chronic heart failure can often not be reached. This secondary analysis of
      the CIBIS-ELD trial was carried out to better understand reasons for not
      achieving target doses. METHODS: Changes in heart rate (HR) and other parameters
      during a 12-week up-titration period in 302 BB naive patients were evaluated in
      the subgroups achieving 12.5, 25, 50, and 100% of the target dose (groups 1, 2,
      3, and 4, respectively). RESULTS: Achieved doses predominantly depended on
      baseline HR (means 68, 74, 76, and 84 bpm in groups 1-4, respectively, P<0.001).
      HR was consistently reduced with each dose level to 65, 63, and 62 bpm in groups
      1-3 and to 71 bpm in group 4 (P<0.001). When adjusted for baseline, HR reduction
      achieved in group 3 was better than in group 4 (difference -5.4 bpm, P<0.05).
      More patients in groups 3/4 than in groups 1/2 improved in NYHA class (P = 0.01).
      NTproBNP increased by 38% in group 4 (P<0.01) but not in the others (P<0.05
      between groups). Changes in blood pressure, six-minute walk distance and self
      rated health were comparable in all groups. CONCLUSIONS: The desired effect of HR
      reduction appears to be a predominant limitation for BB up-titration. Vice versa,
      achieving the target dose may be a sign of insufficient response rather than
      successful treatment. In view of these results and the well-known importance of
      HR for survival, not target doses, but HR control should be given priority in BB
      treatment for heart failure.

PMID- 22133472
TI  - Within-host demographic fluctuations and correlations in early retroviral
      infection.
AB  - In this paper we analyze the demographic fluctuations and correlations present in
      within-host populations of viruses and their target cells during the early stages
      of infection. In particular, we present an exact treatment of a discrete
      population, stochastic, continuous-time master equation description of HIV or
      similar retroviral infection dynamics, employing Monte Carlo simulations. The
      results of calculations employing Gillespie's direct method clearly demonstrate
      the importance of considering the microscopic details of the interactions which
      constitute the macroscopic dynamics. We then employ the tau-leaping approach to
      study the statistical characteristics of infections involving realistic absolute
      numbers of within-host viral and cellular populations, before going on to
      investigate the effect that initial viral population size plays on these
      characteristics. Our main conclusion is that cross-correlations between infected
      cell and virion populations alter dramatically over the course of the infection.
      We suggest that these statistical correlations offer a novel and robust signature
      for the acute phase of retroviral infection.

PMID- 22133473
TI  - Chronic care management for patients with COPD: a critical review of available
      evidence.
AB  - RATIONALE, AIMS AND OBJECTIVES: Clinical diversity and methodological
      heterogeneity exists between studies on chronic care management. This study aimed
      to examine the effectiveness of chronic care management in chronic obstructive
      pulmonary disease (COPD) while taking heterogeneity into account, enabling the
      understanding of and the decision making about such programmes. Three
      investigated sources of heterogeneity were study quality, length of follow-up,
      and number of intervention components. METHODS: We performed a review of
      previously published reviews and meta-analyses on COPD chronic care management.
      Their primary studies that were analyzed as statistical, clinical and
      methodological heterogeneity were present. Meta-regression analyses were
      performed to explain the variances among the primary studies. RESULTS: Generally,
      the included reviews showed positive results on quality of life and
      hospitalizations. Inconclusive effects were found on emergency department visits
      and no effects on mortality. Pooled effects on hospitalizations, emergency
      department visits and quality of life of primary studies did not reach
      significant improvement. No effects were found on mortality. Meta-regression
      showed that the number of components of chronic care management programmes
      explained present heterogeneity for hospitalizations and emergency department
      visits. Four components showed significant effects on hospitalizations, whereas
      two components had significant effects on emergency department visits.
      Methodological study quality and length of follow-up did not significantly
      explain heterogeneity. CONCLUSIONS: This study demonstrated that COPD chronic
      care management has the potential to improve outcomes of care; heterogeneity in
      outcomes was explained. Further research is needed to elucidate the diversity
      between COPD chronic care management studies in terms of the effects measured and
      strengthen the support for chronic care management.

PMID- 22133474
TI  - Boronic acid library for selective, reversible near-infrared fluorescence
      quenching of surfactant suspended single-walled carbon nanotubes in response to
      glucose.
AB  - We describe the high-throughput screening of a library of 30 boronic acid
      derivatives to form complexes with sodium cholate suspended single-walled carbon
      nanotubes (SWNTs) to screen for their ability to reversibly report glucose
      binding via a change in SWNT fluorescence. The screening identifies 4
      cyanophenylboronic acid which uniquely causes a reversible wavelength red shift
      in SWNT emission. The results also identify 4-chlorophenylboronic acid which
      demonstrates a turn-on fluorescence response when complexed with SWNTs upon
      glucose binding in the physiological range of glucose concentration. The
      mechanism of fluorescence modulation in both of these cases is revealed to be a
      photoinduced excited-state electron transfer that can be disrupted by boronate
      ion formation upon glucose binding. The results allow for the elucidation of
      design rules for such sensors, as we find that glucose recognition and
      transduction is enabled by para-substituted, electron-withdrawing phenyl boronic
      acids that are sufficiently hydrophobic to adsorb to the nanotube surface.

PMID- 22133475
TI  - The role of SPINK5 in asthma related physiological events in the airway
      epithelium.
AB  - BACKGROUND: Genetic studies have shown that variants in SPINK5 may be associated
      with atopic diseases and asthma. However, the functional role of SPINK5 protein
      in asthma has not been elucidated. OBJECTIVES: To determine the effects of SPINK5
      on asthma related physiological events such as apoptosis, mucus and cytokine
      production by epithelial cells. METHODS: A549 cells were transfected with SPINK5
      expression vector and stimulated with increasing doses of hydrogen peroxide and
      neutrophil elastase (NE) for measurement of cell viability or apoptosis and
      analysis of mucus production. Cell viability was measured by MTT (3-(4,5
      Dimethylthiazol-2-yl)-2,5- diphenyl-tetrazolium bromide) assay and apoptosis by
      Annexin V/PI staining. Levels of IL-4, IL-6, IL-8, IL-12, IL-13, IFNgamma, IL
      1beta and RANTES were determined by ELISA in cell culture supernatants. Mucus
      production was determined by RT-PCR of the MUC5AC gene and PAS staining in NE
      treated cells. RESULTS: Epithelial cells transfected with SPINK5 expression
      vector produced more IL-6, IL-8 and RANTES compared to non-transfected cells (p <
      0.001, p = 0.003, p < 0.001, respectively). Even though cells transfected with
      SPINK5 vector displayed significantly higher cell death, we have not observed any
      clear effect of SPINK5 on apoptosis. PAS staining showed that SPINK5 slightly
      decreased the mucin production induced by neutrophil elastase in A549 cells.
      However, SPINK5 had no effect on MUC5AC transcription. CONCLUSION: SPINK5 is an
      important molecule in asthma. Its role extends beyond its well known protease
      inhibitor properties.

PMID- 22133476
TI  - Impact of a prophylactic strategy on the incidence of nausea and vomiting after
      general surgery.
AB  - BACKGROUND: This study aimed to evaluate the implementation of a strategy to
      prevent postoperative nausea and vomiting (PONV) in patients undergoing general
      surgery. STUDY DESIGN: Prospective observational study. METHODS: A first period
      was observational. During a second period, a strategy to prevent PONV was based
      on five risk factors (RF) identified after the first phase. From two RF,
      antiemetic treatment was given according to the number of RF. The incidence of
      PONV was recorded in postoperative anaesthesic care unit (PACU) and at the 24th
      postoperative hour (24h). RESULTS: We prospectively enrolled 823 patients.
      Implementation of a prophylactic PONV strategy was associated with a decrease of
      nausea in PACU from 29.9 to 9.8% (P<0.001) and at 24h from 19 to 10.3% (P<0.001).
      Vomiting decreased from 12.4 to 2.3% (P<0.001) in PACU and from 5.6 to 3.7% at
      24h (non-significant). CONCLUSION: Prophylaxis of PONV by the administration of
      antiemetic treatment according to a strategy based on a local risk score was
      efficient and associated with a significant decrease of PONV.

PMID- 22133477
TI  - Impact of complications and comorbidities on treatment costs and health-related
      quality of life of patients with Parkinson's disease.
AB  - BACKGROUND: Data regarding both drug-related and non-drug-related costs in
      patients with Parkinson's disease (PD) are scarce, mainly due to the difficulties
      in data acquisition in experimental designs. Likewise, the reported impact of
      drug costs on total direct costs varies across different studies. In addition,
      the influence of comorbidities on both treatment costs and health-related quality
      of life has not been adequately evaluated. METHODS: A sample of office-based
      neurologists (n=315) in Germany was asked to examine up to five consecutive
      patients with PD (n=1449) on a specified day during the study period. Patients of
      all ages were eligible and their evaluation was performed using standardized
      questionnaires. RESULTS: PD-specific therapy costs increased with the stage of
      the disease, early onset of the disease and disease duration. The major costs
      were due to PD-related therapy, whereas other medications only resulted in minor
      costs. Disease stage mainly influenced direct therapy costs, with an observed
      increase of total daily costs from ?7.3 to ?11.3/day. In addition, disease onset
      at age <65 years resulted in total daily costs of ?11.2 compared to late onset of
      disease (>75 years) with daily therapy costs of ?5.3. In this patient group
      neuropsychiatric comorbidities such as dementia and depression were only
      insufficiently treated. In addition, these comorbidities severely affected health
      related quality of life. CONCLUSION: Therapy costs were influenced by disease
      stage, disease onset as well as present comorbidities. Furthermore, comorbidities
      such as depression and dementia were diagnosed but were not adequately treated.

PMID- 22133478
TI  - Movement disorders in patients with diabetes mellitus.
AB  - Movement disorders are not infrequent in patients with diabetes mellitus. These
      may occur on the basis of both central and peripheral nervous system dysfunction
      and can be secondary to severe hyperglycemia, complications of diabetes or its
      treatment and less often to diseases in which both diabetes and a movement
      disorder are primary manifestations of the same underlying disease. We present a
      typical case of a severe movement disorder complicating diabetes as a springboard
      to review the spectrum of disorders associated with this condition.

PMID- 22133479
TI  - Feasibility and outcome of a web-based self-help intervention for depressive
      symptoms in patients with multiple sclerosis: a pilot study.
AB  - BACKGROUND: Depressive symptoms are highly prevalent among patients with multiple
      sclerosis (MS). Web-based problem solving therapy (PST) is easily accessible and
      showed to be effective in depressed patients. OBJECTIVES: The aims of this pilot
      study were to examine feasibility and outcome (reduction of depressive symptoms)
      of an applied web-based PST intervention in MS patients. METHODS: Forty-four MS
      patients with mild to severe depressive symptoms followed a web-based PST
      intervention. Feasibility was measured by compliance rate and satisfaction
      scales. The Beck Depression Inventory (BDI-II) was used to measure depressive
      symptoms before and after the intervention. RESULTS: The compliance rate was 52%,
      and 85% of the patients rated the quality of the intervention as good or
      excellent. After the intervention, depressive symptoms had significantly
      decreased (BDI-II change: mean=-3.9, p=0.01, d=0.51 in intention-to-treat
      analysis; BDI-II change: mean=-9.0, p<0.001, d=1.50 in completers analysis).
      CONCLUSIONS: This study suggests that applied web-based PST is feasible and
      reduces depressive symptoms in MS patients. Especially MS patients who experience
      disease-related or other barriers to participate in face-to-face counselling
      could benefit. However, ways to increase compliance should be considered. A
      randomized controlled trial is recommended to more extensively investigate
      effectiveness of this intervention in treating depressive symptoms in MS
      patients.

PMID- 22133480
TI  - Spasticity improvement in patients with relapsing-remitting multiple sclerosis
      switching from interferon-beta to glatiramer acetate: the Escala Study.
AB  - BACKGROUND: A recent pilot study suggested spasticity improvement during
      glatiramer acetate (GA) treatment in multiple sclerosis (MS) patients who
      previously received interferon-beta (IFN-beta). OBJECTIVE: To evaluate changes in
      spasticity in MS patients switching from IFN-beta to GA. METHODS: Observational,
      multicentre study in patients with relapsing-remitting MS (RRMS) and spasticity
      switching from IFN-beta to GA. The primary endpoint comprised changes on Penn
      Spasm Frequency Scale (PSFS), Modified Ashworth Scale (MAS), Adductor Tone Rating
      Scale (ATRS), and Global Pain Score (GPS) at months 3 and 6 after starting GA.
      RESULTS: Sixty-eight evaluable patients were included (mean age,41.7+/-9.5 years;
      female,70.6%; mean time from MS diagnosis to starting GA,7.6+/-5.7 years).
      Previous treatments were subcutaneous IFN-beta1a in 42.6% patients, intramuscular
      IFN-beta1a in 41.2% and IFN-beta1b in 32.4%, whose mean durations were 3.5+/-3.3,
      2.7+/-2.5 and 4.4+/-3.6 years, respectively. Statistically significant reductions
      in mean scores on all spasticity measurements were observed from baseline to
      month 3 (PSFS, 1.7+/-0.9 vs 1.4+/-0.6, p<0.01; MAS, 0.7+/-0.5 vs 0.6+/-0.5,
      p<0.01; highest MAS score, 1.9+/-0.8 vs 1.7+/-0.8, p<0.01; ATRS, 1.6+/-0.6 vs
      1.4+/-0.6, p<0.01; GPS, 29.4+/-22.1 vs 24.7+/-19.4, p<0.01) and from baseline to
      month 6 (PSFS, 1.7+/-0.9 vs 1.3+/-0.6, p<0.01; MAS, 0.7+/-0.5 vs 0.5+/-0.5,
      p<0.01; highest MAS score, 1.9+/-0.8 vs 1.5+/-0.9, p<0.01; ATRS, 1.6+/-0.6 vs
      1.3+/-0.6, p<0.01; GPS, 29.4+/-22.1 vs 19.1+/-14.8, p<0.01). CONCLUSION:
      Spasticity improvement in terms of spasm frequency, muscle tone and pain can be
      noted after three months and prolonged for six months of GA treatment.

PMID- 22133481
TI  - Clinical subtypes of anterocollis in parkinsonian syndromes.
AB  - BACKGROUND: Disproportionate anterocollis is a debilitating condition which
      occurs in the later stages of parkinsonian syndromes and for which there is no
      effective therapy. Multiple hypotheses have been proposed to explain its
      underlying etiology, including myopathy of the cervical extensors, and dystonia
      of the cervical flexors. METHODS: We examined the records of 39 patients (8
      prospectively) with anterocollis and parkinsonian syndromes to explore
      demographics, historical and clinical data, findings from electromyography and
      response to therapies. We classified our patients based on whether or not they
      were weak on neck extension and also based on primary diagnosis (PD vs atypical
      parkinsonian syndrome). Demographic, clinical, historical and EMG features are
      reported for each group. RESULTS: There were no significant demographic
      differences between clinical subtypes, or primary diagnosis. Electromyographic
      (EMG) findings demonstrated myopathic changes in both groups, although they were
      more prominent in the group which was weak in extension. Historical features were
      similar between groups except for dopamine agonist use, which was more common in
      the myopathic subgroup (p=0.02). There were no other significant clinical
      differences between clinical subtypes or primary diagnosis with the exception
      that patients with atypical parkinsonian syndromes had more advanced motor
      symptoms. CONCLUSIONS: We conclude that anterocollis is a heterogeneous condition
      in which at least two distinct subtypes exist. Recognizing these subtypes may
      help guide therapy and future research.

PMID- 22133483
TI  - Do you want to play? Factors influencing nurse academics' adoption of simulation
      in their teaching practices.
AB  - Simulation based education (SBE) in healthcare is gaining popularity. It provides
      an opportunity for students to acquire and practice clinical skills in a safe and
      controlled environment and is also a potential solution to alleviating the
      increasing pressure on clinical placement availability. While there is growing
      evidence of the value of simulation to learners there is little understanding of
      the factors that influence academics attitudes towards and choices about the use
      simulation. Through an exploratory research design using semi-structured
      interviews, nurse academics' opinions, experiences and attitudes regarding
      simulation were captured. Thematic analysis was conducted utilising a cross
      comparative approach. Three themes Simulation as a Separate Entity; Getting
      Political, and Academic Adaptation were identified. These themes were then
      explored through the five essential characteristics of innovation identified in
      the persuasion phase of Roger's Diffusion of Innovation Model (1995). The
      findings indicated that in order to successfully integrate simulation into a
      university curriculum, the factors influencing nurse academics' attitudes and
      choices around simulation must be understood and addressed to avoid fragmentation
      of teaching and learning and to support strong learning outcomes.

PMID- 22133484
TI  - Student nurses harassing academics.
AB  - Internationally there is growing awareness that workplace bullying and harassment
      are affecting workers and organisations. However, in England there is limited
      research which examines harassment of faculty by university students. Thus, by
      using Attribution Theory this research explored the experiences of the victims of
      harassment, who were faculty working in schools of Health and Social Care in Post
      1992 Universities in England (1), the perpetrators were undergraduate students.
      Attribution Theory enabled exploration and understanding of faculty perceptions
      of the cause of harassment and the prevention strategies they used. Findings
      showed that faculty perceived that harassment occurred when student stress levels
      were high, which was associated with course and social demands, the changing
      nature of society, and the social political agenda of education.

PMID- 22133482
TI  - Cortical cytasters: a highly conserved developmental trait of Bilateria with
      similarities to Ctenophora.
AB  - BACKGROUND: Cytasters (cytoplasmic asters) are centriole-based nucleation centers
      of microtubule polymerization that are observable in large numbers in the
      cortical cytoplasm of the egg and zygote of bilaterian organisms. In both
      protostome and deuterostome taxa, cytasters have been described to develop during
      oogenesis from vesicles of nuclear membrane that move to the cortical cytoplasm.
      They become associated with several cytoplasmic components, and participate in
      the reorganization of cortical cytoplasm after fertilization, patterning the
      antero-posterior and dorso-ventral body axes. PRESENTATION OF THE HYPOTHESIS: The
      specific resemblances in the development of cytasters in both protostome and
      deuterostome taxa suggest that an independent evolutionary origin is unlikely. An
      assessment of published data confirms that cytasters are present in several
      protostome and deuterostome phyla, but are absent in the non-bilaterian phyla
      Cnidaria and Ctenophora. We hypothesize that cytasters evolved in the lineage
      leading to Bilateria and were already present in the most recent common ancestor
      shared by protostomes and deuterostomes. Thus, cytasters would be an ancient and
      highly conserved trait that is homologous across the different bilaterian phyla.
      The alternative possibility is homoplasy, that is cytasters have evolved
      independently in different lineages of Bilateria. TESTING THE HYPOTHESIS: So far,
      available published information shows that appropriate observations have been
      made in eight different bilaterian phyla. All of them present cytasters. This is
      consistent with the hypothesis of homology and conservation. However, there are
      several important groups for which there are no currently available data. The
      hypothesis of homology predicts that cytasters should be present in these groups.
      Increasing the taxonomic sample using modern techniques uniformly will test for
      evolutionary patterns supporting homology, homoplasy, or secondary loss of
      cytasters. IMPLICATIONS OF THE HYPOTHESIS: If cytasters are homologous and highly
      conserved across bilateria, their potential developmental and evolutionary
      relevance has been underestimated. The deep evolutionary origin of cytasters also
      becomes a legitimate topic of research. In Ctenophora, polyspermic fertilization
      occurs, with numerous sperm entering the egg. The centrosomes of sperm pronuclei
      associate with cytoplasmic components of the egg and reorganize the cortical
      cytoplasm, defining the oral-aboral axis. These resemblances lead us to suggest
      the possibility of a polyspermic ancestor in the lineage leading to Bilateria.

PMID- 22133485
TI  - Simulation-based smoking cessation intervention education for undergraduate
      nursing students.
AB  - Smoking is one of the most important preventable risk factors that contributes to
      premature death from many tobacco-related diseases. Clinicians should offer and
      provide effective smoking cessation interventions to their smoking patients. Yet,
      few clinicians receive training in smoking cessation intervention. This one
      group, quasi-experimental study was conducted to describe a simulation-based
      training of smoking cessation intervention and to evaluate its effectiveness on
      nursing students' self-efficacy in performing smoking cessation intervention,
      based on 5-As recommended by the United States Department of Health and Human
      Services. In addition, nursing students' experience, attitude and perceived
      barriers of smoking cessation intervention were also described. Among the 21
      students (mean age: 21.6 +/- 2.0 years), 86% were female, 62% were in their third
      year and 1% were current smokers. Most of students believed the health benefits
      of smoking cessation (100.0-66.7%) and were well educated about health risks of
      smoking (81.0-61.9%). However, few were taught (33.3-14.4%) and practiced (28.6
      0.0%) smoking cessation intervention. Students reported that they should be
      actively involved in smoking cessation for patients (100.0-95.2%), but lack of
      knowledge and skills were the main barriers (90.5-85.7%). The simulation-based
      training of smoking cessation intervention improved nursing students' self
      efficacy in seven out of nine skills of smoking cessation intervention (mean
      scores of pre- vs. post-intervention: 30.86 +/- 3.80 vs. 34.05 +/- 5.10; paired
      t=2.298, p=.027). These findings indicate that simulation could be effectively
      used in teaching smoking cessation intervention education delivered to nursing
      students.

PMID- 22133486
TI  - Computer-assisted anatomically placed double-bundle ACL reconstruction: an in
      vitro experiment with different tension angles for the AM and the PL graft.
AB  - Anterior cruciate ligament reconstruction techniques are evolving with
      innovations like double-bundle (DB) grafts and computer assistance. The current
      DB techniques do not appear to make the clinical difference yet. Insight in
      various techniques may lead to better results. In this study, the anterior laxity
      of a DB reconstruction with an anteromedial (AM) graft fixated in 90 degrees  of
      flexion and a posterolateral (PL) graft fixated in 20 degrees  and computer
      assisted anatomically placed femoral attachments was compared to normal values
      and single-bundle grafts. In 8 fresh-frozen human cadaveric knees, the anterior
      laxity was tested from 0 degrees  to 90 degrees  flexion, with a 100 Newton (N)
      anterior tibial load in joints with (1) intact ACL, (2) torn ACL, (3) single
      bundle (SB) graft tensed with 15 N in 20 degrees , (4) anatomic AM graft tensed
      with 15 N in 90 degrees , (5) anatomic PL graft tensed with 15 N in 20 degrees ,
      and (6) anatomic DB graft (4+5). All reconstructions caused a posterior position
      of the tibia. Relative to the normal anterior laxity, the single-bundle
      techniques showed significantly increased laxities: The SB technique in 0 degrees
      (+1.1 mm) and 15 degrees  (+1.7 mm); The AM reconstructions in 45 degrees  (+1.6
      mm) and 90 degrees  (+1.5 mm); The PL reconstructions in all angles (from +1.4 to
      +2.3 mm), except in 0 degrees . The anatomic DB technique showed no significantly
      increased laxities and restored normal laxity in all angles.

PMID- 22133487
TI  - Fetal development, mechanobiology and optimal control processes can improve
      vascular tissue regeneration in bioreactors: an integrative review.
AB  - Vascular tissue engineering aims to regenerate blood vessels to replace diseased
      arteries for cardiovascular patients. With the scaffold-based approach, cells are
      seeded on a scaffold showing specific properties and are expected to proliferate
      and self-organize into a functional vascular tissue. Bioreactors can
      significantly contribute to this objective by providing a suitable environment
      for the maturation of the tissue engineered blood vessel. It is recognized from
      the mechanotransduction principles that mechanical stimuli can influence the
      protein synthesis of the extra-cellular matrix thus leading to maturation and
      organization of the tissues. Up to date, no bioreactor is especially conceived to
      take advantage of the mechanobiology and optimize the construct maturation
      through an advanced control strategy. In this review, experimental strategies in
      the field of vascular tissue engineering are detailed, and a new approach
      inspired by fetal development, mechanobiology and optimal control paradigms is
      proposed. In this new approach, the culture conditions (i.e. flow,
      circumferential strain, pressure frequency, and others) are supposed to
      dynamically evolve to match the maturity of vascular constructs and maximize the
      efficiency of the regeneration process. Moreover, this approach allows the
      investigation of the mechanisms of growth, remodeling and mechanotransduction
      during the culture.

PMID- 22133488
TI  - Wireless sensor networks for indoor air quality monitoring.
AB  - The purpose of this study is to build an indoor air quality monitoring system
      based on wireless sensor networks (WSNs) technology. The main functions of the
      system include (1) remote parameter adjustment and firmware update mechanism for
      the sensors to enhance the flexibility and convenience of the system, (2) sensor
      nodes are designed by referring to the IEEE 1451.4 standard. This way, sensor
      nodes can automatically adjust and be plug and play, and (3) calibration method
      to strength the measurement value's sensitivity and accuracy. The experimental
      results show that transmission speed improves 30% than Trickle, transmission
      volume reduced to 42% of the original volume, updating task in 5*5 network
      topology can be executed 1.79 times and power consumption reduced to 30%. When
      baseline drifts, we can use the firmware update mechanism to adjust the reference
      value. The way can reduce error percentage from 15% to 7%.

PMID- 22133489
TI  - The polymorphisms of T cell-specific TBX21 and STAT4 genes may contribute to the
      susceptibility of Chinese individuals to aplastic anemia.
AB  - T cell-specific T-box transcription factor gene (TBX21) and signal transducer and
      activator of transcription 4 (STAT4) have been suggested as 2 candidate genes for
      conferring susceptibility to autoimmunity. We herein hypothesized that the
      polymorphisms of TBX21 and STAT4 genes might contribute to the susceptibility of
      Chinese individuals to aplastic anemia (AA) as T cell-mediated immune disease
      characterized by hypoplasia and pancytopenia. We investigated the distributions
      of TBX21 (T-1993C and T-1514C) and STAT4 (rs7574862) polymorphisms in 202 adult
      patients with AA and 195 healthy controls by polymerase chain reaction
      restriction fragment length polymorphism. The frequencies of T-1993C (but not T
      1514C) genotype and allele distribution were significantly higher in AA patients
      than in controls. The T allele (TT + TG genotypes) of STAT4 variant rs7574865 was
      associated with increased susceptibility of Chinese people to AA. Our results
      indicated that single nucleotide polymorphisms in TBX21 and STAT4 might
      contribute to susceptibility to AA in the Chinese population.

PMID- 22133490
TI  - A psoriasiform drug eruption induced by polyethylene glycol interferon-alpha-2b,
      successfully treated by narrow band ultraviolet B therapy.

PMID- 22133491
TI  - Localization of Ascaridia galli larvae in the jejunum of chickens 3 days post
      infection.
AB  - The normal habitat of the parasitic stages of Ascaridia galli is in the small
      intestine of poultry but the exact localization is poorly understood. Therefore,
      a histological study was conducted in order to localize the larvae during the
      early phase of infection. Six layer pullets seven-week old were infected orally
      with 20,000 embryonated A. galli eggs each, whereas four chickens were left as un
      infected controls. At necropsy 3 days after infection the first half of
      jejunum/ileum was divided into two equally sized sections (J1 and J2). After
      taking samples for histology from the middle of J1 and J2 and the junction
      between these determined JX, the two sections were subjected to parasitological
      examination. A higher number of A. galli larvae were recovered from section J2
      than J1 and the majority of larvae were recovered from the most profound layers.
      Based on histology 144 larvae were identified and their location was noted. The
      highest number of larvae was observed in the JX sample as compared to J1 and J2
      (P<0.001). Most of them were located in the profound crypt zone of the mucosa
      (51%) as compared to the other zones (P<0.05). The number of larvae was higher in
      the lumen (63%) compared to the epithelium (32%) and lamina propria (5%)
      (P<0.001). A significantly higher number of eosinophils were found in lamina
      propria of the infected group compared to the control group (P<0.001). This
      experiment clearly showed that only few larvae had penetrated the epithelium and
      were positioned in the lamina propria at 3 days post infection. It was far more
      common that the larvae were localized within the epithelium or in the lumen of
      the crypts. It is therefore suggested that at least in this early phase "mucosal
      phase" is a more appropriate term to be used for the A. galli larval localization
      as compared to the term "histotrophic phase" currently used in many textbooks.

PMID- 22133492
TI  - Long-term effects of intravenous iloprost in patients with idiopathic pulmonary
      arterial hypertension deteriorating on non-parenteral therapy.
AB  - BACKGROUND: The majority of patients with idiopathic pulmonary arterial
      hypertension (IPAH) in functional classes II and III are currently being treated
      with non-parenteral therapies, including endothelin receptor antagonists (ERA),
      phosphodiesterase (PDE)-5 inhibitors, inhaled iloprost or combinations of these
      substances. If these treatments fail, current guidelines recommend the addition
      of parenteral prostanoid therapy. There is, however, limited evidence for the
      efficacy of parenteral prostanoids when added to combinations of non-parenteral
      therapies. METHODS: In this retrospective, multicentre study we collected data
      from consecutive IPAH patients receiving intravenous iloprost in addition to
      optimized non-parenteral therapy between Jan 2002 and Dec 2009. Analyses included
      6 min walk distance (6MWD), functional class, need for transplantation, and
      survival. RESULTS: During the observation period, 50 patients were treated with
      intravenous iloprost in addition to non-parenteral therapy; 44% of the patients
      were on dual combination therapy and 52% on triple combination. Three months
      after initiation of iloprost, functional class had improved in 24% of the
      patients and the median 6MWD had increased from 289 m to 298 m (n.s.). During the
      observation period, 22 patients (44%) died and 14 (28%) underwent lung
      transplantation. The probabilities of LuTx-free survival at 1, 3 and 5 years
      following iloprost initiation were 38%, 17% and 17%, respectively. A 6MWD < 300 m
      and persistent functional class IV at 3 months after initiation of intravenous
      iloprost were predictors of an adverse outcome. CONCLUSION: In essence, late
      initiation of intravenous iloprost in IPAH patients who previously failed to
      respond to non-parenteral therapies appears to be of limited efficacy in the
      majority patients. Alternative therapeutic options are currently not available,
      underlying the need for the development of new drugs.

PMID- 22133494
TI  - Electrophysiological and behavioral correlates of stable automatic semantic
      retrieval in aging.
AB  - Previous studies have shown both declining and stable semantic-memory abilities
      during healthy aging. There is consistent evidence that semantic processes
      involving controlled mechanisms weaken with age. In contrast, results of aging
      studies on automatic semantic retrieval are often inconsistent, probably due to
      methodological limitations and differences. The present study therefore examines
      age-related alterations in automatic semantic retrieval and memory structure with
      a novel combination of critical methodological factors, i.e., the selection of
      subjects, a well-designed paradigm, and electrophysiological methods that result
      in unambiguous signal markers. Healthy young and elderly participants performed
      lexical decisions on visually presented word/non-word pairs with a stimulus onset
      asynchrony (SOA) of 150 ms. Behavioral and electrophysiological data were
      measured, and the N400-LPC complex, an event-related potential component
      sensitive to lexical-semantic retrieval, was analyzed by power and topographic
      distribution of electrical brain activity. Both age groups exhibited semantic
      priming (SP) and concreteness effects in behavioral reaction time and the
      electrophysiological N400-LPC complex. Importantly, elderly subjects did not
      differ significantly from the young in their lexical decision and SP performances
      as well as in the N400-LPC SP effect. The only difference was an age-related
      delay measured in the N400-LPC microstate. This could be attributed to existing
      age effects in controlled functions, as further supported by the replicated age
      difference in word fluency. The present results add new behavioral and
      neurophysiological evidence to earlier findings, by showing that automatic
      semantic retrieval remains stable in global signal strength and topographic
      distribution during healthy aging.

PMID- 22133495
TI  - Distinct critical cerebellar subregions for components of verbal working memory.
AB  - A role for the cerebellum in cognition has been proposed based on studies
      suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies
      are limited in the determination of the detailed organisation of cerebellar
      subregions that are critical for different aspects of cognition. In this study we
      examined the correlation between cognitive performance and cerebellar integrity
      in a specific degeneration of the cerebellar cortex: Spinocerebellar Ataxia type
      6 (SCA6). The results demonstrate a critical relationship between verbal working
      memory and grey matter density in superior (bilateral lobules VI and crus I of
      lobule VII) and inferior (bilateral lobules VIIIa and VIIIb, and right lobule IX)
      parts of the cerebellum. We demonstrate that distinct cerebellar regions subserve
      different components of the prevalent psychological model for verbal working
      memory based on a phonological loop. The work confirms the involvement of the
      cerebellum in verbal working memory and defines specific subsystems for this
      within the cerebellum.

PMID- 22133496
TI  - Aortic event rate in the Marfan population: a cohort study.
AB  - BACKGROUND: Optimal management, including timing of surgery, remains debated in
      Marfan syndrome because of a lack of data on aortic risk associated with this
      disease. METHODS AND RESULTS: We used our database to evaluate aortic risk
      associated with standardized care. Patients who fulfilled the international
      criteria, had not had previous aortic surgery or dissection, and came to our
      center at least twice were included. Aortic measurements were made with
      echocardiography (every 2 years); patients were given systematic beta-blockade
      and advice about sports activities. Prophylactic aortic surgery was proposed when
      the maximal aortic diameter reached 50 mm. Seven hundred thirty-two patients with
      Marfan syndrome were followed up for a mean of 6.6 years. Five deaths and 2
      dissections of the ascending aorta occurred during follow-up. Event rate
      (death/aortic dissection) was 0.17%/y. Risk rose with increasing aortic diameter
      measured within 2 years of the event: from 0.09%/y per year (95% confidence
      interval, 0.00-0.20) when the aortic diameter was <40 mm to 0.3% (95% confidence
      interval, 0.00-0.71) with diameters of 45 to 49 mm and 1.33% (95% confidence
      interval, 0.00-3.93) with diameters of 50 to 54 mm. The risk increased 4 times at
      diameters >=50 mm. The annual risk dropped below 0.05% when the aortic diameter
      was <50 mm after exclusion of a neonatal patient, a woman who became pregnant
      against our recommendation, and a 72-year-old woman with previous myocardial
      infarction. CONCLUSIONS: Risk of sudden death or aortic dissection remains low in
      patients with Marfan syndrome and aortic diameter between 45 and 49 mm. Aortic
      diameter of 50 mm appears to be a reasonable threshold for prophylactic surgery.

PMID- 22133497
TI  - Coating graphene paper with 2D-assembly of electrocatalytic nanoparticles: a
      modular approach toward high-performance flexible electrodes.
AB  - The development of flexible electrodes is of considerable current interest
      because of the increasing demand for modern electronics, portable medical
      products, and compact energy devices. We report a modular approach to fabricating
      high-performance flexible electrodes by structurally integrating 2D-assemblies of
      nanoparticles with freestanding graphene paper. We have shown that the 2D array
      of gold nanoparticles at oil-water interfaces can be transferred on freestanding
      graphene oxide paper, leading to a monolayer of densely packed gold nanoparticles
      of uniform sizes loaded on graphene oxide paper. One major finding is that the
      postassembly electrochemical reduction of graphene oxide paper restores the
      ordered structure and electron-transport properties of graphene, and gives rise
      to robust and biocompatible freestanding electrodes with outstanding
      electrocatalytic activities, which have been manifested by the sensitive and
      selective detection of two model analytes: glucose and hydrogen peroxide
      (H(2)O(2)) secreted by live cells. The modular nature of this approach coupled
      with recent progress in nanocrystal synthesis and surface engineering opens new
      possibilities to systematically study the dependence of catalytic performance on
      the structural parameters and chemical compositions of the nanocrystals.

PMID- 22133498
TI  - Comparison of Canadian and American diagnostic radiology certification
      examinations: a survey of the examinees perceptions.

PMID- 22133499
TI  - Dry-thermophilic anaerobic digestion of organic fraction of municipal solid
      waste: methane production modeling.
AB  - The influence of particle size and organic matter content of organic fraction of
      municipal solid waste (OFMSW) in the overall kinetics of dry (30% total solids)
      thermophilic (55 degrees C) anaerobic digestion have been studied in a semi
      continuous stirred tank reactor (SSTR). Two types of wastes were used: synthetic
      OFMSW (average particle size of 1mm; 0.71 g Volatile Solids/g waste), and OFMSW
      coming from a composting full scale plant (average particle size of 30 mm; 0.16 g
      Volatile Solids/g waste). A modification of a widely-validated product-generation
      kinetic model has been proposed. Results obtained from the modified-model
      parameterization at steady-state (that include new kinetic parameters as K,
      Y(pMAX) and theta(MIN)) indicate that the features of the feedstock strongly
      influence the kinetics of the process. The overall specific growth rate of
      microorganisms (MU(max)) with synthetic OFMSW is 43% higher compared to OFMSW
      coming from a composting full scale plant: 0.238 d(-1) (K=1.391 d(-1);
      Y(pMAX)=1.167 L CH(4)/gDOC(c); theta(MIN)=7.924 days) vs. 0.135 d(-1) (K=1.282 d(
      1); Y(pMAX)=1.150 L CH(4)/gDOC(c); theta(MIN)=9.997 days) respectively. Finally,
      it could be emphasized that the validation of proposed modified-model has been
      performed successfully by means of the simulation of non-steady state data for
      the different SRTs tested with each waste.

PMID- 22133500
TI  - Discussing the future of dental materials, processes and products.

PMID- 22133501
TI  - In their own words: adolescent views on ADHD and their evolving role managing
      medication.
AB  - OBJECTIVE: Up to 90% of adolescents with attention deficit hyperactivity disorder
      (ADHD) remain functionally impaired, yet less than half continue to take
      medication. The objective of this study was to gain a detailed understanding of
      how adolescents with ADHD contribute to medication treatment decisions. METHODS:
      Forty-four adolescents with ADHD aged 13 to 18 years old participated in 1 of 7
      focus groups. An experienced facilitator used a semi-structured focus group guide
      to prompt discussion which was audio-recorded and transcribed verbatim. We coded
      transcripts using an inductive approach. Thematic saturation was reached after
      the seventh focus group. RESULTS: Adolescents assumed increased responsibility
      for managing medication as they matured and developed insight into the functional
      impact of ADHD and medication on their lives. Insights were often formed by
      contrasting time spent on and off medication. ADHD impacted functioning in the
      following domains: academics, social interactions and relationships, creativity,
      and driving skills. Select domains were relevant for some adolescents but not
      others. Adolescents described different roles that they played in managing
      medication as well as strategies they used to exert autonomy over medication use.
      Side effects were common and contributed to negative feelings toward medication.
      Some adolescents had begun to use medication selectively. Many expressed
      uncertainty about future use of medication. CONCLUSIONS: Adolescents assume an
      increasing role in managing medication for ADHD. Well-structured and coordinated
      trials stopping medication and measuring outcomes relevant to adolescents,
      parents, teachers, doctors, and/or other stakeholders may help ensure a
      developmentally appropriate transition from family to self-management of ADHD.

PMID- 22133502
TI  - Acute myeloid leukemia secondary to oxaliplatin treatment for esophageal cancer.

PMID- 22133504
TI  - Season of birth and risk of developing idiopathic Parkinson's disease.

PMID- 22133503
TI  - Acquisition of chemical recognition cues facilitates integration into ant
      societies.
AB  - BACKGROUND: Social insects maintain the integrity of their societies by
      discriminating between colony members and foreigners through cuticular
      hydrocarbon (CHC) signatures. Nevertheless, parasites frequently get access to
      social resources, for example through mimicry of host CHCs among other
      mechanisms. The origin of mimetic compounds, however, remains unknown in the
      majority of studies (biosynthesis vs. acquisition). Additionally, direct evidence
      is scarce that chemical mimicry is indeed beneficial to the parasites (e.g., by
      improving social acceptance). RESULTS: In the present study we demonstrated that
      the kleptoparasitic silverfish Malayatelura ponerophila most likely acquires CHCs
      directly from its host ant Leptogenys distinguenda by evaluating the transfer of
      a stable-isotope label from the cuticle of workers to the silverfish. In a second
      experiment, we prevented CHC pilfering by separating silverfish from their host
      for six or nine days. Chemical host resemblance as well as aggressive rejection
      behaviour by host ants was then quantified for unmanipulated and previously
      separated individuals. Separated individuals showed reduced chemical host
      resemblance and they received significantly more aggressive rejection behaviour
      than unmanipulated individuals. CONCLUSION: Our study clarifies the mechanism of
      chemical mimicry in a social insect parasite in great detail. It shows
      empirically for the first time that social insect parasites are able to acquire
      CHCs from their host. Furthermore, it demonstrates that the accuracy of chemical
      mimicry can be crucial for social insect parasites by enhancing social acceptance
      and, thus, allowing successful exploitation. We discuss the results in the light
      of coevolutionary arms races between parasites and hosts.

PMID- 22133505
TI  - Increased serum levels of miR-1266 in patients with psoriasis vulgaris.
AB  - MicroRNAs (miRNAs) are post-transcriptional regulators that bind to complementary
      sequences in the 3' UTRs of mRNAs, leading to gene silencing, and their serum
      levels can be useful biomarkers for diagnosis, prognosis and therapeutic value in
      various diseases. Although miRNAs are thought to be involved in the pathogenesis
      of human diseases, little is known about miRNAs in psoriasis. Recently, psoriasis
      has attracted attention for its characteristics as a Th17 disease; the expression
      of IL-17 is increased in lesional skin and serum. We hypothesized that miRNAs
      contribute to the mechanism underlying the overexpression of IL-17. Therefore,
      serum levels of miR-1266, a putative regulator of IL-17A, in psoriasis patients
      were determined with the expectation that miR-1266 levels may be decreased in
      these patients, which may result in induction of IL-17. However, real-time PCR
      demonstrated that serum miR-1266 levels were considerably higher in psoriasis
      patients than in healthy control subjects. Furthermore, miR-1266 levels showed
      weak inverse correlations with Psoriasis Area Severity Index scores and body
      surface areas of involved skin. Taken together, serum miR-1266 may have potential
      for a new disease marker. miR-1266 is not likely to regulate IL-17A expression
      directly, but may be involved in the pathogenesis of psoriasis by regulating
      other target molecules.

PMID- 22133506
TI  - Antibody response to allelic variants of 19kDa fragment of MSP-1: recognition of
      a variant and protection associated with ethnicity in Assam, India.
AB  - Evidence suggests association of anti MSP-1(19) antibodies with protection from
      clinical malaria. However, the target epitope was reported to vary with respect
      to response to conserved or variant epitopes in different studies. We have
      investigated here humoral response of naturally exposed individuals of Tibeto
      Burman and Austro-Asiatic ethnic groups to E-TSR and Q-KNG variants of MSP-1(19)
      in comparison to whole merozoite extract (WME) of local strain of Plasmodium
      falciparum in a longitudinal prospective cohort study. The association of
      antibodies in relation to risk of infection and disease severity was determined.
      A relatively lower seropositivity to MSP1(19) peptides derived from 3D7 and FVO
      strains in comparison to whole merozoite extract of local P. falciparum strain
      was observed. Recognition of Q-KNG variant was markedly lower in TB (p<0.0001)
      indicating a role of ethnicity. The Tea tribes of Austro-Asiatic affinity had
      higher antibody response (E-TSR; p=0.038 and Q-KNG; p=0.004) and equally
      recognized the two variants. A reduced risk of clinical infection in high
      transmission summer season was seen in presence of anti MSP-1(19) antibodies
      (p=0.013) and antibody level was predictive of risk of clinical malaria
      (ROC=0.729). Anti E-TSR antibodies were inversely associated to disease severity
      at KTE (lambda(2)p=0.013; t-test p=0.032). The present study demonstrated
      antibody response to MSP-1(19) was associated with protection from frequent
      episodes of malaria and disease severity and that the host genetic background was
      important factor in response to MSP-1(19) allelic variant.

PMID- 22133507
TI  - Risk perception and communication in vaccination decisions: a fuzzy-trace theory
      approach.
AB  - The tenets of fuzzy-trace theory, along with prior research on risk perception
      and risk communication, are used to develop a process model of vaccination
      decisions in the era of Web 2.0. The theory characterizes these decisions in
      terms of background knowledge, dual mental representations (verbatim and gist),
      retrieval of values, and application of values to representations in context.
      Lack of knowledge interferes with the ability to extract the essential meaning,
      or gist, of vaccination messages. Prevention decisions have, by definition, a
      status quo option of "feeling okay." Psychological evidence from other prevention
      decisions, such as cancer screening, indicates that many people initially
      mentally represent their decision options in terms of simple, categorical gist: a
      choice between (a) a feeling-okay option (e.g., the unvaccinated status quo)
      versus (b) taking up preventive behavior that can have two potential categorical
      outcomes: feeling okay or not feeling okay. Hence, applying the same theoretical
      rules as used to explain framing effects and the Allais paradox, the decision to
      get a flu shot, for example, boils down to feeling okay (not sick) versus feeling
      okay (not sick) or not feeling okay (sick, side effects, or death). Because
      feeling okay is superior to not feeling okay (a retrieved value), this
      impoverished gist supports choosing not to have the flu vaccine. Anti-vaccination
      sources provide more coherent accounts of the gist of vaccination than official
      sources, filling a need to understand rare adverse outcomes.

PMID- 22133508
TI  - Impact of rotavirus vaccination on epidemiological dynamics in England and Wales.
AB  - Rotavirus infection causes severe gastroenteritis (RVGE) in children worldwide.
      Its disease burden has been reduced in countries where mass vaccination programs
      have been introduced. However, England and Wales have not yet implemented such a
      mass vaccination program. This paper uses a dynamic model to predict the effect
      of a mass vaccination program in England and Wales beginning in the fall of 2011.
      The dynamic model is parameterized with country-specific data for the
      introduction of a rotavirus vaccine. We report the impact of vaccination, in both
      the short- and long-term, on disease incidence reduction, timing of seasonal
      epidemics and the level of herd protection. Our results predict that vaccination
      can reduce the burden of severe RVGE by 70% and delay the rotavirus epidemic peak
      by two and a half months with a coverage of 95%. Our calculations further show
      that herd protection accounts for about a quarter of the reduction in RVGE
      incidence. If vaccine-induced protection does not wane over three years, severe
      RVGE in children under five years of age could be eliminated within two years
      after the introduction of vaccination. This work lays the foundation for policy
      makers to determine the impact of a mass vaccination program against rotavirus in
      England and Wales.

PMID- 22133509
TI  - Focus and breadth of cellular immune responses elicited by a heterologous insert
      prime-boost vaccine regimen in rhesus monkeys.
AB  - The global sequence diversity of HIV-1 presents a daunting challenge for vaccine
      development. We investigated whether a heterologous insert prime-boost regimen
      could expand global coverage by selectively boosting cellular immune responses to
      conserved epitopes. Rhesus monkeys were primed and boosted with recombinant
      adenovirus vectors expressing homologous or heterologous HIV-1 Gag sequences that
      were optimized to focus responses on highly conserved epitopes. We observed
      comparable responses directed to specific regions of the Gag protein in all
      experimental groups without evidence of improved coverage or expanded breadth in
      the heterologous insert group. These data suggest that antigen-independent
      factors contribute to the immunodominance patterns of vaccine-elicited cellular
      immune responses.

PMID- 22133510
TI  - Blockade of B7-H1 enhances dendritic cell-mediated T cell response and antiviral
      immunity in HBV transgenic mice.
AB  - Dendritic cells (DCs) have been identified as the most effective antigen
      presenting cell (APC), much attention has been directed toward the use of DCs in
      vaccine strategies for the treatment of cancer or chronic virus infection. B7-H1
      (PD-L1) is a ligand for programmed cell death-1 (PD-1) and does not bind to other
      CD28 family members, it is expressed on resting and upregulated on activated B,
      T, myeloid, and dendritic cells (DCs). The overwhelming number of studies
      supports the role of B7-H1 as a negative regulator of T cell responses. RNA
      interference (RNAi) is a mechanism for sequence-specific posttranscriptional
      inhibition of gene expression via double stranded RNA molecules and it has
      recently been applied to mammalian cells with the use of small interfering RNAs
      (siRNAs). In the study, transfection of DCs with siRNA specific for B7-H1 gene
      resulted in the blockade of the expression of B7-H1 on DCs. The allostimulatory
      activity of DCs could be enhanced by silencing of B7-H1 on DCs. Blockade of B7-H1
      on DCs inhibited the production of IFN-gamma and IL-10 but not IL-2 and IL-4 in
      mixed lymphocyte reaction (MLR). HBV specific peptide-pulsed DCs could break
      tolerance and trigger specific CTL responses, the level of HBsAg and HBV DNA in
      sera of HBV transgenic mice decreased, whereas blockade of B7-H1 on DCs augmented
      the effects. These data strongly support the concept that blockade of B7-H1 can
      enhance DC-mediated antiviral immune responses.

PMID- 22133511
TI  - Factors associated with uptake of seasonal and pandemic influenza vaccine among
      clinical risk groups in the UK: an analysis using the General Practice Research
      Database.
AB  - BACKGROUND: Influenza vaccine uptake rates are low compared with uptake rates of
      many other vaccines. It is unclear how this differs between risk groups in the
      population and between pandemic and non-pandemic influenza vaccines. AIM: This
      study sought to estimate uptake rates of pandemic and seasonal influenza vaccines
      among clinical risk groups in the UK during the 2009/2010 influenza season and to
      identify predictors of vaccine uptake in this cohort. METHODS: Uptake rates were
      calculated using data from the UK General Practice Research Database (GPRD).
      Predictors of vaccination were identified using a modified Poisson regression
      with robust standard error estimates. RESULTS: Uptake of pandemic influenza
      vaccine in clinical risk groups was 40.3% and uptake of seasonal influenza
      vaccine was 61.3%. Factors found to be predictive of seasonal and pandemic
      influenza vaccination included age and the total number of underlying health
      conditions an individual had. At risk individuals in those age groups in which
      universal vaccination of the general population was recommended were more likely
      to have been vaccinated than individuals in age groups in which only clinical
      risk groups were recommended for vaccination; hence children in clinical risk
      groups were more likely to receive pandemic than seasonal influenza vaccine. In
      older people, having a history of Guillain Barre syndrome was associated with a
      reduced likelihood of receipt of both seasonal (IRR(adj) 0.83, CI(95) 0.77-0.90)
      and pandemic influenza vaccines (IRR(adj) 0.82, CI(95) 0.73-0.92). DISCUSSION:
      Uptake of pandemic influenza vaccine was lower than that of seasonal influenza
      vaccine among those at a clinically high risk of influenza related morbidity.
      This suggests that vaccination strategies may need to be altered during future
      pandemics. Recommending universal vaccination within age categories in which
      there is a large proportion of high risk individuals could be considered as this
      may result in higher uptake among clinical risk groups.

PMID- 22133512
TI  - Enhanced tumor immunity of WT1 peptide vaccination by interferon-beta
      administration.
AB  - To induce and activate tumor-associated antigen-specific cytotoxic T lymphocytes
      (CTLs) for cancer immunity, it is important not only to select potent CTL
      epitopes but also to combine them with appropriate immunopotentiating agents.
      Here we investigated whether tumor immunity induced by WT1 peptide vaccination
      could be enhanced by IFN-beta. For the experimental group, C57BL/6 mice were
      twice pre-treated with WT1 peptide vaccine, implanted with WT1-expressing C1498
      cells, and treated four times with WT1 peptide vaccine at one-week intervals.
      During the vaccination period, IFN-beta was injected three times a week. Mice in
      control groups were treated with WT1 peptide alone, IFN-beta alone, or PBS alone.
      The mice in the experimental group rejected tumor cells and survived
      significantly longer than mice in the control groups. The overall survival on day
      75 was 40% for the mice treated with WT1 peptide+IFN-beta, while it was 7, 7, and
      0% for those treated with WT1 peptide alone, IFN-beta alone or PBS alone,
      respectively. Induction of WT1-specific CTLs and enhancement of NK activity were
      detected in splenocytes from mice in the experimental group. Furthermore,
      administration of IFN-beta enhanced expression of MHC class I molecules on the
      implanted tumor cells. In conclusion, our results showed that co-administration
      of WT1 peptide+IFN-beta enhanced tumor immunity mainly through the induction of
      WT1-specific CTLs, enhancement of NK activity, and promotion of MHC class I
      expression on the tumor cells. WT1 peptide vaccination combined with IFN-beta
      administration can thus be expected to enhance the clinical efficacy of WT1
      immunotherapy.

PMID- 22133513
TI  - Duration of maternally derived antibody against measles: a seroepidemiological
      study of infants aged under 8 months in Qinghai, China.
AB  - To estimate the sero-prevalence of protective maternal measles antibodies among
      young infants and examine patterns of waning immunity in one of the poorest
      provinces in China, infants aged under 8 months and their mothers were randomly
      selected by multi-stage probabilistic sampling and blood samples were collected.
      Measles-specific IgG antibodies were measured in all serum samples by enzyme
      linked immunosorbent assay. We determined measles-specific antibody titres for
      477 pairs of infants and their mothers. After excluding 44 sub-clinical measles
      infection in infants, the measles antibody titres were ?1:200, ?1:800, and
      ?1:3200 in 79.2%, 46.9%, and 17.8% of the 433 infants, respectively. The
      proportion of infants with titre ?1:800 declined with age from 90.2% in newborns
      to 45.5% and 14.9% in the fourth and eighth month, respectively. Among the 433
      mothers, measles antibody titres were ?1:800 in 94.0%. Multivariate regression
      analysis showed that residence, mother's antibody levels and infant's age were
      significantly associated with infants' having a measles antibody titre ?1:800.
      The relatively rapid decay of protective antibody in infants suggests that an
      earlier administration of the first dose of measles vaccination should be
      considered in China and a high quality interventional study is needed to decide
      the optimal schedule of measles immunization.

PMID- 22133514
TI  - NY DEC takes on fracking.

PMID- 22133516
TI  - The role of personality and traumatic events in cortisol levels--where does PTSD
      fit in?
AB  - BACKGROUND: Studies of cortisol in post-traumatic stress disorder (PTSD) have
      yielded mixed results. We hypothesize that personality traits and traumatic
      experiences could be the confounders of cortisol measures and disease symptoms.
      METHOD: This study was a part of a broader project in which simultaneous
      psychological and biological investigations were carried out in hospital
      conditions on 400 male participants categorized by four groups: (A) 133 with
      current PTSD, (B) 66 with lifetime PTSD, (C) 102 trauma controls, and (D) 99
      healthy controls (matched by age and education). Cortisol and ACTH were measured
      in blood samples taken hourly from 22:00 h to 09:00 h, with an additional sample
      at 07:30 h (resting state and morning rise). The next night, dexamethasone
      (0.5mg) suppression test was performed. RESULTS: No significant differences in
      basal cortisol and ACTH were found between study groups. The trait
      Conscientiousness, negatively modulated by Extraversion (assessed by NEO
      Personality Inventory-Revised) was found to correlate with cortisol (but not with
      ACTH). Group differences are found on suppression. Structural equation modeling
      shows excellent fit only when the paths (influences) from Conscientiousness to
      basal cortisol and from traumatic events to suppression are present. The paths
      connecting suppression and PTSD symptoms do not contribute. CONCLUSIONS: Two
      sources of differences of hypothalamo-pituitary-adrenocortical axis functioning
      are implied, both only indirectly connected to PTSD. It seems that basal cortisol
      secretion is associated more tightly with personality (introvertively modulated
      Conscientiousness), while the regulation by glucocorticoid receptor system is
      sensitized by repeated traumatic situations.

PMID- 22133515
TI  - Leptin and interleukin-6 alter the function of mesolimbic dopamine neurons in a
      rodent model of prenatal inflammation.
AB  - Maternal inflammation during critical stages of gestation is thought to underlie
      the link between prenatal infection and several neurodevelopmental psychiatric
      disorders in the offspring, including schizophrenia. Increased activity of
      mesolimbic dopamine (DA) neurons, a hallmark of psychosis, is found in offspring
      of rodents exposed to a prenatal inflammatory challenge but it is unclear how
      this effect is elicited. Using an experimental model of localized aseptic
      inflammation with turpentine oil (TURP) we sought to establish whether
      circulating interleukin-6 (IL-6) and leptin play a role in the effects of
      prenatal inflammation on DA neurons. Both mediators are involved in the systemic
      inflammatory response to immunogens, with IL-6 mediating the early phase,
      followed by leptin in the late phase of the response. Maternal treatment with
      TURP at gestational day (GD) 15 enhanced the locomotor response to the DA
      indirect agonist, amphetamine (AMPH), increased the expression of tyrosine
      hydroxylase (TH), an enzyme involved in DA synthesis, DA levels and the
      expression of the post-synaptic protein spinophilin in the nucleus accumbens
      (NAcc) in the adult offspring. All of these alterations were totally abolished by
      co-treating the pregnant dams with a neutralizing IL-6 antiserum. Neutralization
      of maternal leptin prevented the enhanced behavioral sensitization and elevation
      of DA and spinophilin in the NAcc but spared other changes regulated by IL-6,
      such as increased NAcc TH levels and acute locomotor response to AMPH. Our
      results provide novel evidence to suggest that prenatal surges in both maternal
      circulating IL-6 and leptin contribute to the appearance of sensitized DA
      function in the adult offspring.

PMID- 22133518
TI  - Inducing novel electronic properties in <112> Ge nanowires by means of variations
      in their size, shape and strain: a first-principles computational study.
AB  - The size, shape and strain dependences of the electronic properties of germanium
      nanowires (GeNWs) along the <112> direction are investigated using first
      principles calculations based on density functional theory. The structures of
      relatively stable <112> GeNWs of different sizes have been revealed. The <112>
      GeNWs exhibit direct band gaps when the cross-sectional aspect ratio of the (111)
      to the (110) facet is larger than 1. For a relatively high stability of the <112>
      GeNWs, the compressive strain tends to widen the band gap, whereas tensile strain
      tends to narrow it. The variation in band gaps originates from the different
      responses of valence and conduction bands to externally applied strain. Our
      results demonstrate that size, shape and strain can be used in unison to
      effectively tune the band structures of GeNWs, providing useful guidance for
      designing future nanoelectronic devices.

PMID- 22133517
TI  - Age-dependent and -independent associations between depression, anxiety, DHEAS,
      and cortisol: from the MIPH Industrial Cohort Studies (MICS).
AB  - There is a well-established link between dysphoric mood and endocrine
      dysregulation, but the strength of this association may vary with age. In order
      to investigate this possibility we assessed anxiety and depression with overnight
      urinary cortisol and plasma dehydroepiandrosterone-sulphate (DHEAS) in 608
      factory employees ranging between 21 and 62 years. As expected, DHEAS declined
      with age (r=-0.54, P<0.001) while there was a modest age-related increase in
      nocturnal cortisol (r=0.17, P<0.001). Depressive symptoms were associated with
      higher nocturnal cortisol (beta=0.19, P<0.001), independent of age. While the
      association between anxiety and cortisol (age by anxiety interaction: beta=0.11,
      P<0.05) became stronger with age, there was a similar decline in the
      DHEAS/cortisol ratio in high-anxious middle-aged adults (beta=-0.10, P=0.018).
      The current findings suggest that dysphoric mood, and in particular anxiety, may
      exacerbate the effects of aging on cortisol release. Prospective studies are
      needed to determine the causal relations between dysphoric mood, cortisol and
      DHEAS across the lifespan.

PMID- 22133519
TI  - Visual detection of gene mutations based on isothermal strand-displacement
      polymerase reaction and lateral flow strip.
AB  - Here, we describe a simple and sensitive approach for visual detection of gene
      mutations based on isothermal strand-displacement polymerase reactions (ISDPR)
      and lateral flow strip (LFS). The concept was first demonstrated by detecting the
      R156H-mutant gene of keratin 10 in Epidermolytic hyperkeratosis (EHK). In the
      presence of biotin-modified hairpin DNA and digoxin-modified primer, the R156H
      mutant DNA triggered the ISDPR to produce numerous digoxin- and biotin-attached
      duplex DNA products. The product was detected on the LFS through dual
      immunoreactions (anti-digoxin antibody on the gold nanoparticle (Au-NP) and
      digoxin on the duplex, anti-biotin antibody on the LFS test zone and biotin on
      the duplex). The accumulation of Au-NPs produced the characteristic red band,
      enabling visual detection of the mutant gene without instrumentation. After
      systematic optimization of the ISDPR experimental conditions and the parameters
      of the assay, the current approach was capable of detecting as low as 1-fM R156H
      mutant DNA within 75 min without instrumentation. Differentiation of R156H- and
      R156C-mutant DNA on the R156 mutation site was realized by using fluorescein- and
      biotin-modified hairpin probes in the ISDPR process. The approach thus provides a
      simple, sensitive, and low-cost tool for the detection of gene mutations.

PMID- 22133520
TI  - Availability of a rich source of sodium during the perinatal period programs the
      fluid balance restoration pattern in adult offspring.
AB  - Osmoregulatory mechanisms can be vulnerable to electrolyte and/or endocrine
      environmental changes during the perinatal period, differentially programming the
      developing offspring and affecting them even in adulthood. The aim of this study
      was to evaluate whether availability of hypertonic sodium solution during the
      perinatal period may induce a differential programming in adult offspring
      osmoregulatory mechanisms. With this aim, we studied water and sodium intake
      after Furosemide-sodium depletion in adult offspring exposed to hypertonic sodium
      solution from 1 week before mating until postnatal day 28 of the offspring, used
      as a perinatal manipulation model [PM-Na group]. In these animals, we also
      identified the cell population groups in brain nuclei activated by Furosemide
      sodium depletion treatment, analyzing the spatial patterns of Fos and Fos
      vasopressin immunoreactivity. In sodium depleted rats, sodium and water intake
      were significantly lower in the PM-Na group vs. animals without access to
      hypertonic sodium solution [PM-Ctrol group]. Interestingly, when comparing the
      volumes consumed of both solutions in each PM group, our data show the expected
      significant differences between both solutions ingested in the PM-Ctrol group,
      which makes an isotonic cocktail; however, in the PM-Na group there were no
      significant differences in the volumes of both solutions consumed after
      Furosemide-sodium depletion, and therefore the sodium concentration of total
      fluid ingested by this group was significantly higher than that in the PM-Ctrol
      group. With regard to brain Fos immunoreactivity, we observed that Furosemide
      sodium depletion in the PM-Na group induced a higher number of activated cells in
      the subfornical organ, ventral subdivision of the paraventricular nucleus and
      vasopressinergic neurons of the supraoptic nucleus than in the PM-Ctrol animals.
      Moreover, along the brainstem, we found a decreased number of sodium depletion
      activated cells within the nucleus of the solitary tract of the PM-Na group. Our
      data indicate that early sodium availability induces a long-term effect on fluid
      drinking and on the cell activity of brain nuclei involved in the control of
      hydromineral balance. These results also suggest that availability of a rich
      source of sodium during the perinatal period may provoke a larger anticipatory
      response in the offspring, activating the vasopressinergic system and reducing
      thirst after water and sodium depletion, as a result of central osmosensitive
      mechanism alterations.

PMID- 22133522
TI  - [Cry wolf].
AB  - Systemic lupus erythematosus (SLE) is an uncommon disease in children and
      adolescents but far from being unknown. The disease's symptoms are often non
      specific and vague at first and clinicians must suspect SLE without the more
      specific symptoms. Treatment should be initiated as soon as possible to delay or
      prevent serious complications. This case demonstrates the history of a young boy
      who needed medical attention at the Children's Hospital of Iceland because of
      joint pain, swollen lymph nodes and fatigue. The epidemiology, diagnostic
      criteria, treatment and prognosis of children diagnosed with SLE are reviewed.

PMID- 22133521
TI  - Genetic sensitivity to the caregiving context: the influence of 5httlpr and BDNF
      val66met on indiscriminate social behavior.
AB  - Evidence that gene*environment interactions can reflect differential sensitivity
      to the environmental context, rather than risk or resilience, is increasing. To
      test this model, we examined the genetic contribution to indiscriminate social
      behavior, in the setting of a randomized controlled trial of foster care compared
      to institutional rearing. Children enrolled in the Bucharest Early Intervention
      Project (BEIP) were assessed comprehensively before the age of 30 months and
      subsequently randomized to either care as usual (CAUG) or high quality foster
      care (FCG). Indiscriminate social behavior was assessed at four time points,
      baseline, 30 months, 42 months and 54 months of age, using caregiver report with
      the Disturbances of Attachment Interview (DAI). General linear mixed-effects
      models were used to examine the effect of the interaction between group status
      and functional polymorphisms in Brain Derived Neurotrophic Factor (BDNF) and the
      Serotonin Transporter (5htt) on levels of indiscriminate behavior over time.
      Differential susceptibility, relative to levels of indiscriminate behavior, was
      demonstrated in children with either the s/s 5httlpr genotype or met 66 BDNF
      allele carriers. Specifically children with either the s/s 5httlpr genotype or
      met66 carriers in BDNF demonstrated the lowest levels of indiscriminate behavior
      in the FCG and the highest levels in the CAUG. Children with either the long
      allele of the 5httlpr or val/val genotype of BDNF demonstrated little difference
      in levels of indiscriminate behaviors over time and no group*genotype
      interaction. Children with both plasticity genotypes had the most signs of
      indiscriminate behavior at 54 months if they were randomized to the CAUG in the
      institution, while those with both plasticity genotypes randomized to the FCG
      intervention had the fewest signs at 54 months. Strikingly children with no
      plasticity alleles demonstrated no intervention effect on levels of
      indiscriminate behavior at 54 months. These findings represent the first genetic
      associations reported with indiscriminate social behavior, replicate previous
      gene*gene*environment findings with these polymorphisms, and add to the growing
      body of literature supporting a differential susceptibility model of
      gene*environment interactions in developmental psychopathology.

PMID- 22133523
TI  - [Neglected tropical diseases - review].
AB  - Neglected tropical diseases include a variety of infectious diseases. This review
      shortly describes the most common diseases. Those infected usually live at a low
      socioeconomic status and rarely have access to satisfactory health care. The
      neglected diseases are common and have a high burden of disease. In comparison to
      HIV, malaria and tuberculosis this group of diseases is in fact neglected.
      Certain diseases within the group are more neglected than others. Investment for
      research does not appear to be decided in proportion to burden of disease. Much
      can be gained by extermination of these diseases. The solution is to integrate
      improvement of living standards and battling diseases. Iceland has a role to
      play.

PMID- 22133524
TI  - [Developing the journal - new guidelines for authors of research articles].

PMID- 22133525
TI  - [University of Iceland ranked among top 300 universities in the world].

PMID- 22133526
TI  - [Medication use among community-dwelling older Icelanders. Population-based study
      in urban and rural areas].
AB  - OBJECTIVE: To describe medication use among older community-dwelling Icelanders
      by collecting information on number of medicine, polypharmacy (>5 medications),
      and medications by ATC categories. Moreover, to explore the relationship between
      medication use and various influential factors emphasizing residency in urban and
      rural areas. MATERIAL AND METHODS: Population-based, cross-sectional study.
      Participants were randomly selected from the National registry in one urban
      (n=118) and two rural (n=68) areas. INCLUSION CRITERIA: 1) >= 65 years old, 2)
      community-dwelling, 3) able to communicate verbally. Information on medication
      use was obtained from each person's medication list and interviews. A
      questionnaire and five standardized instruments were used to assess the potential
      influencing factors. RESULTS: On average, participants used 3.9 medications and
      prevalence of polypharmacy was 41%. Men used 3.5 medications on average and women
      4.4 (p=0.018). Compared to rural residents, urban residents had fewer medical
      diagnoses, better mobility, less pain, and fewer depressive symptoms. By
      controlling for the effects of these variables, more medications were associated
      with urban living (p<0.001) and more medical diagnoses (p<0.001). Likewise,
      adjusted odds for polypharmacy increased with urban residency (p=0.023) and more
      medical diagnoses (p=0.005). Urban residency, more medical diagnoses, higher age,
      and male gender were related to use of drugs for blood and blood forming organs.
      CONCLUSION: The results reveal an unexplained regional difference in medications
      use by older Icelanders. Further studies are required on why urban residents use
      at least equal amount of medications as rural residents despite better scores on
      health assessments.

PMID- 22133527
TI  - [Lung volume reduction surgery for severe pulmonary emphysema in Iceland].
AB  - INTRODUCTION: Lung volume reduction surgery (LVRS) can benefit patients with
      severe emphysema. The aim of this study was to evaluate the outcome of LVRS
      performed in Iceland. MATERIALS AND METHODS: A prospective study of 16
      consecutive patients who underwent bilateral LVRS through median sternotomy
      between January 1996 and December 2008. All patients had disabling dyspnea, lung
      hyperinflation, and emphysema with upper lobe predominance. Preoperatively all
      patients underwent pulmonary rehabilitation. Spirometry, lung volumes, arterial
      blood gases and exercise capacity were measured before and after surgery. Mean
      follow-up time was 8.7 years. RESULTS: Mean age was 59.2 +/- 5.9 years. All
      patients had a history of heavy smoking. There was no perioperative mortality and
      survival was 100%, 93%, and 63% at 1, 5, and 10 years, respectively. The forced
      expiratory volume in 1 second (FEV1) and the forced vital capacity (FVC) improved
      significantly after surgery by 35% (p<0.001) and 14% (p<0.05), respectively. The
      total lung capacity, residual volume and partial pressure of CO2 also showed
      statistically significant improvements but exercise capacity, O2 consumption and
      diffusing capacity of the lung for CO did not change. Prolonged air leak (>= 7
      days) was the most common complication (n=7). Five patients required reoperation,
      most commonly for sternal dehiscence (n=4). CONCLUSION: In this small prospective
      study, FEV1 and FVC increased and lung volumes and PaCO2 improved after LVRS.
      Long term survival was satisfactory although complications such as reoperations
      for sternal dehiscence were common and hospital stay therefore often prolonged.

PMID- 22133528
TI  - Letters to the editor: like a rolling stone?

PMID- 22133529
TI  - Paraoxonase 1 genetic polymorphisms and susceptibility to breast cancer: a meta
      analysis.
AB  - AIM: The paraoxonase 1 gene (PON1, MIN: 168820) is a member of the multifactorial
      antioxidant enzyme paraoxonase family (EC 3.1.1.2). Two common functional single
      nucleotide polymorphisms L55M (dbSNP: rs854560) and Q192R (dbSNP: rs662) have
      been identified in the coding region of PON1. Several studies have investigated
      the associations between polymorphisms of PON1 and susceptibility to breast
      cancer, but have yielded apparently conflicting results. We therefore carried out
      a meta-analysis of published studies to clarify this inconsistency and to
      establish a comprehensive picture of the relationship between PON1 gene variants
      and breast cancer risk. METHOD: Overall six eligible studies were identified.
      Summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using
      fixed and random-effect models. RESULTS: In our meta-analysis, the presence of
      the R allele was associated with decreased risk of breast cancer (QR+RR compared
      to QQ genotype, summary OR=0.57, 95% CI: 0.49-0.67, P<0.001). Both heterozygosity
      (OR=1.32, 95% CI: 1.10-1.58, P=0.002) and homozygosity (OR=2.16, 95% CI: 1.75
      2.68, P<0.001) for the 55M allele were associated with increased risk of breast
      cancer. Also there was a significant linear trend in risk associated with zero,
      one, and two 55M alleles (chi(2)=54.2, P<0.001). CONCLUSION: The present study
      showed that PON1 M and Q alleles are associated with a higher risk of breast
      cancer. Individuals having MM and QQ genotypes have a lower level and lower
      detoxification activity of the PON1 enzyme, which may increase the vulnerability
      of the breast to genetic damage by reducing the ability to detoxify inflammatory
      oxidants, as well as dietary carcinogens.

PMID- 22133530
TI  - Passive cervical spine flexion: the effect of age and gender.
AB  - BACKGROUND: Previous studies reported passive cervical range of motion under
      unknown loading conditions or with minimal detail of subject positioning.
      Additionally, such studies have not quantitatively ensured the absence of active
      muscle during passive measurements. For the purpose of validating biomechanical
      models the loading condition, initial position, and muscle activation must be
      clearly defined. A method is needed to quantify the passive range of motion
      properties of the cervical spine under controlled loading conditions,
      particularly in the pediatric population where normative clinical and model
      validation data is limited. METHODS: Healthy female pediatric (6-12years; n=10),
      male pediatric (6-12years; n=9), female adult (21-40years; n=10), and male adult
      (20-36years; n=9) volunteers were enrolled. Subjects with restrained torsos and
      lower extremities were exposed to a maximum 1g inertial load in the posterior
      anterior direction, such that the head-neck complex flexed when subjects relaxed
      their neck musculature. Surface electromyography monitored the level of muscle
      relaxation. A multi-camera 3-D target tracking system captured passive neck
      flexion angle of the head relative to the thoracic spine. General estimating
      equations detected statistical differences across age and gender. FINDINGS:
      Passive cervical spine flexion equaled 111.0 degrees  (SD 8.0 degrees ) for
      pediatric females, 102.8 degrees  (SD 7.8 degrees ) for adult females, 103.8
      degrees  (SD 12.7 degrees ) for pediatric males, and 93.7 degrees  (SD 9.9
      degrees ) for adult males. Passive neck flexion significantly decreased with age
      in both genders (P<0.01). Females exhibited significantly greater flexion than
      males (P<0.01). INTERPRETATION: This study contributes normative data for
      clinical use, biomechanical modeling, and injury prevention tool development.

PMID- 22133532
TI  - National Healthcare Safety Network (NHSN) Report, data summary for 2010, device
      associated module.

PMID- 22133533
TI  - Beliefs about hand hygiene: a survey in medical students in their first clinical
      year.
AB  - Medical students were asked regarding knowledge and beliefs on hand hygiene
      before entering the clinical phase of education. By this, we noticed a lack of
      knowledge concerning the correct indications for hand disinfection. Regardless of
      previous experience in hospitals, the medical students expected that the
      compliance towards hand hygiene would be worse in more experienced physicians and
      senior consultants--who are often considered to be role models for medical
      students.

PMID- 22133534
TI  - Role of quit supporters and other factors associated with smoking abstinence in
      adolescent smokers: a prospective study on Quitline users in the Republic of
      Korea.
AB  - The aim of this study elucidated the effectiveness of Quitline among adolescent
      smokers, as well as other factors associated with adolescent smoking cessation in
      the Republic of Korea. For 642 adolescent Quitline users aged 13-19 years, the
      information on demographic characteristics, smoking and cessation related
      factors, and cessation outcome was collected. Cox proportional hazard models were
      applied. 13.4% of boys and 6.6% of girls maintained smoking cessation for 1 year.
      Having a high level of self-efficacy had a preventive effect on relapse in both
      genders. Boys with parents or other family members as quit supporters, and boys
      with a higher number of past cessation attempts, were more likely to relapse. It
      was even more pronounced among boys who reported low self-efficacy. Relapse was
      increased with marginal significance among girls with parents or other family
      members as quit supporters. It is evident that Quitline is an effective way to
      encourage adolescent smoking cessation in Korea. Reinforcing self-efficacy and
      enhancing the cooperative behaviors of parents or other family member quit
      supporters could be additional contributors for maintaining cessation among
      adolescent smokers who want to quit.

PMID- 22133535
TI  - Polariton trap in microcavities with metallic mirrors.
AB  - In planar microcavities with metallic mirrors the spectra of cavity polaritons
      may be strongly modified by the presence of a surface plasmon interacting with
      transverse-magnetic (TM)-polarized cavity modes. In particular, for certain
      parameters of the cavity, a minimum in the dispersion of the TM-polarized
      polariton may develop, which is located in the non-radiative part of the
      spectrum. This minimum may serve as a very effective trap for polariton
      population at high non-resonant excitation of the cavity.

PMID- 22133537
TI  - Keep it clean: hospital-acquired infections in children.

PMID- 22133536
TI  - Risk and causes of paediatric hospital-acquired bacteraemia in Kilifi District
      Hospital, Kenya: a prospective cohort study.
AB  - BACKGROUND: In sub-Saharan Africa, community-acquired bacteraemia is an important
      cause of illness and death in children. Our aim was to establish the magnitude
      and causes of hospital-acquired (nosocomial) bacteraemia in African children.
      METHODS: We reviewed prospectively collected surveillance data of 33,188
      admissions to Kilifi District Hospital, Kenya, between April 16, 2002, and Sept
      30, 2009. We defined bacteraemia as nosocomial if it occurred 48 h or more after
      admission. We estimated the per-admission risk, daily rate, effect on mortality,
      and microbial cause of nosocomial bacteraemia and analysed risk factors by
      multivariable Cox regression. The effect on morbidity was measured as the
      increase in hospital stay by comparison with time-matched patients without
      bacteraemia. FINDINGS: The overall risk of nosocomial bacteraemia during this
      period was 5.9/1000 admissions (95% CI 5.2-6.9) but we recorded an underlying
      rise in risk of 27% per year. The incidence was 1.0/1000 days in hospital (0.87
      1.14), which is about 40 times higher than that of community-acquired bacteraemia
      in the same region. Mortality in patients with nosocomial bacteraemia was 53%,
      compared with 24% in community-acquired bacteraemia and 6% in patients without
      bacteraemia. In survivors, nosocomial bacteraemia lengthened hospital stay by
      10.1 days (3.0-17.2). Klebsiella pneumoniae, Escherichia coli, Staphylococcus
      aureus, Acinetobacter spp, group D streptococci, and Pseudomonas aeruginosa
      accounted for three-quarters of nosocomial infections. Nosocomial bacteraemia was
      significantly associated with severe malnutrition (hazard ratio 2.52, 95% CI 1.79
      3.57) and blood transfusion in children without severe anaemia (4.99; 3.39-7.37).
      INTERPRETATION: Our findings show that although nosocomial bacteraemia is rare,
      it has serious effects on morbidity and mortality, and the microbiological causes
      are distinct from those of community-acquired bacteraemia. Nosocomial infections
      are largely unrecognised or undocumented as a health risk in low-income
      countries, but they are likely to become public health priorities as awareness of
      their occurrence increases and as other prominent childhood diseases are
      progressively controlled. FUNDING: Wellcome Trust.

PMID- 22133538
TI  - Neonatal screening for lysosomal storage disorders.

PMID- 22133539
TI  - Neonatal screening for lysosomal storage disorders: feasibility and incidence
      from a nationwide study in Austria.
AB  - BACKGROUND: The interest in neonatal screening for lysosomal storage disorders
      has increased substantially because of newly developed enzyme replacement
      therapies, the need for early diagnosis, and technical advances. We tested for
      Gaucher's disease, Pompe's disease, Fabry's disease, and Niemann-Pick disease
      types A and B in an anonymous prospective nationwide screening study that
      included genetic mutation analysis to assess the practicality and appropriateness
      of including these disorders in neonatal screening panels. METHODS: Specimens
      from dried blood spots of 34,736 newborn babies were collected consecutively from
      January, 2010 to July, 2010, as part of the national routine Austrian newborn
      screening programme. Anonymised samples were analysed for enzyme activities of
      acid beta-glucocerebrosidase, alpha-galactosidase, alpha-glucosidase, and acid
      sphingomyelinase by electrospray ionisation tandem mass spectrometry. Genetic
      mutation analyses were done in samples with suspected enzyme deficiency.
      FINDINGS: All 34,736 samples were analysed successfully by the multiplex
      screening assay. Low enzyme activities were detected in 38 babies. Mutation
      analysis confirmed lysosomal storage disorders in 15 of them. The most frequent
      mutations were found for Fabry's disease (1 per 3859 births), followed by Pompe's
      disease (1 per 8684), and Gaucher's disease (1 per 17,368). The positive
      predictive values were 32% (95% CI 16-52), 80% (28-99), and 50% (7-93),
      respectively. Mutational analysis detected predominantly missense mutations
      associated with a late-onset phenotype. INTERPRETATION: The combined overall
      proportion of infants carrying a mutation for lysosomal storage disorders was
      higher than expected. Neonatal screening for lysosomal storage disorders is
      likely to raise challenges for primary health-care providers. Furthermore, the
      high frequency of late-onset mutations makes lysosomal storage disorders a broad
      health problem beyond childhood. FUNDING: Austrian Ministry of Health, Family,
      and Women.

PMID- 22133540
TI  - Stormwater strategies: cities prepare aging infrastructure for climate change.

PMID- 22133541
TI  - Effects induced by cannabinoids on monoaminergic systems in the brain and their
      implications for psychiatric disorders.
AB  - The endocannabinoid system and CB(1) receptors participate in the control of
      emotional behavior and mood through a functional coupling with the classic
      monoaminergic systems. In general, the acute stimulation of CB(1) receptors
      increases the activity (spontaneous firing rate) of noradrenergic (NE),
      serotonergic (5-HT) and dopaminergic (DA) neurons as well as the synthesis and/or
      release of the corresponding neurotransmitter in specific brain regions. Notably,
      the antagonist/inverse agonist rimonabant (SR141617A) can decrease the basal
      activity of NE and 5-HT neurons, suggesting a tonic/constitutive regulation of
      these neuronal systems by endocannabinoids acting at CB(1) receptors.
      Monoaminergic systems are modulated via CB(1) receptors by direct or indirect
      effects depending on the localization of this inhibitory receptor, which can be
      present on monoaminergic neurons themselves and/or inhibitory (GABAergic) and/or
      excitatory (glutamatergic) regulatory neurons. The repeated stimulation of CB(1)
      receptors is not associated with the induction of tolerance (receptor
      desensitization) on the activity of NE, 5-HT and DA neurons, in contrast to
      chronic agonist effects on neurotransmitter synthesis and/or release in some
      brain regions. CB(1) receptor desensitization may alter the direct and/or
      indirect effects of cannabinoid drugs modulating the functionality of
      monoaminergic systems. The sustained activation of monoaminergic neurons by
      cannabinoid drugs can also be related to changes in the function of presynaptic
      inhibitory alpha(2)-adrenoceptors or 5-HT(1A) receptors (autoreceptors and
      heteroreceptors), whose sensitivity is downregulated or upregulated upon chronic
      CB(1) agonist exposure. The functional interactions between endocannabinoids and
      monoaminergic systems in the brain indicate a potential role for CB(1) receptor
      signaling in the neurobiology of various psychiatric disorders, including major
      depression and schizophrenia as the major syndromes.

PMID- 22133542
TI  - Re-evaluation of the concept of chronic, latent, magnesium deficiency.

PMID- 22133543
TI  - Role of interleukin 6 and alpha-globulins in differentiating Alzheimer and
      vascular dementias.
AB  - BACKGROUND: Inflammatory mechanisms and immune activation have been hypothesized
      to play a role in the pathogenesis of age-associated diseases, including
      Alzheimer's disease. PURPOSE: The evaluation of inflammatory markers in patients
      with dementia, and to determine whether these markers can be used to
      differentiate between vascular dementia (VD) and Alzheimer's dementia (AD).
      PATIENTS AND METHODS: Twenty demented patients (10 AD and 10 VD) and 20 non
      demented controls were subjected to clinical evaluation, MRI brain scans and
      laboratory tests, including interleukin (IL) 6, C-reactive protein and serum
      protein electrophoresis. RESULTS: The results of this study revealed that serum
      levels of IL-6 and C-reactive protein were significantly elevated among patients
      with both types of dementia compared to normal elderly subjects. Although the
      mean IL-6 level was higher in patients with AD compared to patients with VD, this
      difference was not significant. The cutoff value at which the serum level of IL-6
      gave maximum sensitivity and specificity was 14.25 pg/ml. Moreover, alpha1- and
      alpha2-globulins were able to discriminate between AD and VD (being significantly
      higher in AD). CONCLUSION: IL-6 levels could be used to differentiate dementia
      from normal aging. Moreover, alpha1- and alpha2-globulins could differentiate
      between AD and VD. It can be concluded that inflammation plays an important role
      in both types of dementia.

PMID- 22133544
TI  - A tandem mass spectrometric study of bile acids: interpretation of fragmentation
      pathways and differentiation of steroid isomers.
AB  - Bile acids are steroids with a pentanoic acid substituent at C-17. They are the
      terminal products of cholesterol excretion, and play critical physiological roles
      in human and animals. Bile acids are easy to detect but difficult to identify by
      using mass spectrometry due to their poly-ring structure and various
      hydroxylation patterns. In this study, fragmentation pathways of 18 free and
      conjugated bile acids were interpreted by using tandem mass spectrometry. The
      analyses were conducted on ion trap and triple quadrupole mass spectrometers.
      Upon collision-induced dissociation, the conjugated bile acids could cleave into
      glycine or taurine related fragments, together with the steroid skeleton.
      Fragmentations of free bile acids were further elucidated, especially by
      atmospheric pressure chemical ionization mass spectrometry in positive ion mode.
      Aside from universally observed neutral losses, eliminations occurred on bile
      acid carbon rings were proposed for the first time. Moreover, four isomeric 5beta
      cholanic acid hydroxyl derivatives (3alpha,6alpha-, 3alpha,7beta-, 3alpha,7alpha
      , and 3alpha,12alpha-) were differentiated using electrospray ionization in
      negative ion mode: 3alpha,7beta-OH substituent inclined to eliminate H(2)O and
      CH(2)O(2) groups; 3alpha,6alpha-OH substituent preferred neutral loss of two
      H(2)O molecules; 3alpha,12alpha-OH substituent apt to lose the carboxyl in the
      form of CO(2) molecule; and 3alpha,7alpha-OH substituent exhibited no further
      fragmentation after dehydration. This study provided specific interpretation for
      mass spectra of bile acids. The results could contribute to bile acid analyses,
      especially in clinical assays and metabonomic studies.

PMID- 22133545
TI  - Bile acid-cysteamine conjugates: structural properties, gelation, and toxicity
      evaluation.
AB  - Design, synthesis, and characterization of six novel bile acid-cysteamine
      conjugates together with investigation of their structural studies, gelation
      properties, and preliminary toxicity evaluation, are reported. Solid state
      properties of selected compounds were studied by means of X-ray diffraction and
      (13)C CPMAS NMR spectroscopy. N-(2-thioethyl)-3alpha,7alpha,12alpha-trihydroxy
      5beta-cholan-24-amide was shown to exhibit (pseudo)polymorphism, and a single
      crystal structure of its non-stoichiometric hydrate is reported herein. Cholyl
      and dehydrocholyl derivatives bearing three functionalities in their steroidal
      backbone were shown to undergo self-assembly leading to gelation in certain
      organic solvents. Preliminary morphology studies of the formed gels by scanning
      electron microscopy (SEM) were performed. The standard model mouse fibroblast
      cell line together with the MTT and NR tests were utilized for evaluating the
      toxicity of the prepared compounds. Lithocholyl, ursodeoxycholyl, and
      dehydrocholyl derivatives turned out to be relatively non-toxic in the conditions
      studied.

PMID- 22133547
TI  - Microfluidics for single cell analysis.
AB  - Substantial evidence shows that the heterogeneity of individual cells within a
      genetically identical population can be critical to their chance of survival.
      Methods that use average responses from a population often mask the difference
      from individual cells. To fully understand cell-to-cell variability, a complete
      analysis of an individual cell, from its live state to cell lysates, is
      essential. Highly sensitive detection of multiple components and high throughput
      analysis of a large number of individual cells remain the key challenges to
      realise this aim. In this context, microfluidics and lab-on-a-chip technology
      have emerged as the most promising avenue to address these challenges. In this
      review, we will focus on the recent development in microfluidics that are aimed
      at total single cell analysis on chip, that is, from an individual live cell to
      its gene and proteins. We also discuss the opportunities that microfluidic based
      single cell analysis can bring into the drug discovery process.

PMID- 22133546
TI  - Synthesis and biological activities of vitamin D-like inhibitors of CYP24
      hydroxylase.
AB  - Selective inhibitors of CYP24A1 represent an important synthetic target in a
      search for novel vitamin D compounds of therapeutic value. In the present work,
      we show the synthesis and biological properties of two novel side chain modified
      2-methylene-19-nor-1,25(OH)(2)D(3) analogs, the 22-imidazole-1-yl derivative 2
      (VIMI) and the 25-N-cyclopropylamine compound 3 (CPA1), which were efficiently
      prepared in convergent syntheses utilizing the Lythgoe type Horner-Wittig
      olefination reaction. When tested in a cell-free assay, both compounds were found
      to be potent competitive inhibitors of CYP24A1, with the cyclopropylamine analog
      3 exhibiting an 80-1 selective inhibition of CYP24A1 over CYP27B1. Addition of 3
      to a mouse osteoblast culture sustained the level of 1,25(OH)(2)D(3), further
      demonstrating its effectiveness in CYP24A1 inhibition. Importantly, the in vitro
      effects on human promyeloid leukemia (HL-60) cell differentiation by 3 were
      nearly identical to those of 1,25(OH)(2)D(3) and in vivo the compound showed low
      calcemic activity. Finally, the results of preliminary theoretical studies
      provide useful insights to rationalize the ability of analog 3 to selectively
      inhibit the cytochrome P450 isoform CYP24A1.

PMID- 22133548
TI  - Repeatability of intraoperative central corneal and residual stromal thickness
      measurement using a handheld ultrasound pachymeter.
AB  - PURPOSE: To determine and compare the repeatability of intraoperative central
      corneal thickness (CCT) and residual stromal bed thickness measurements using a
      handheld ultrasound (US) pachymeter. SETTING: London Vision Clinic, London,
      United Kingdom. DESIGN: Comparative evaluation of a diagnostic test or
      technology. METHODS: This study comprised eyes that had laser in situ
      keratomileusis retreatment by flap lift in which handheld US pachymetry (Corneo
      Gage Plus 50 MHz) had been performed intraoperatively. In each case, 5
      consecutive measurements were obtained centrally immediately before and after the
      flap was lifted. The within-eye repeatability was calculated as the standard
      deviation of the 5 repeated measurements for the CCT measurements and the central
      residual stromal thickness (RST) measurements. RESULTS: The study evaluated 134
      eyes (79 patients). The mean CCT was 467 MUm +/- 40 (SD) (range 393 to 577 MUm).
      The repeatability of CCT measurements was 6.83 MUm, the coefficient of
      repeatability was 13.40 MUm, and the coefficient of variation (CoV) was 1.46%.
      The mean central RST was 335 +/- 46 MUm (range 259 to 465 MUm). The repeatability
      of central RST measurements was 4.91 MUm, the coefficient of repeatability was
      9.62 MUm, and the CoV was 1.46%. CONCLUSION: The repeatability of intraoperative
      handheld US pachymetry was similar between measurements of CCT and measurements
      of central RST; the CoV was 1.46% in both cases.

PMID- 22133550
TI  - Inguinal, iliac and obturator lymphadenectomy.

PMID- 22133549
TI  - Ultrasound-induced corneal incision contracture survey in the United States and
      Canada.
AB  - PURPOSE: To ascertain factors associated with corneal incision contracture (wound
      burn) secondary to phacoemulsification in the United States and Canada. SETTING:
      John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA, and
      University of Toronto, Toronto, Ontario, Canada. DESIGN: Cross-sectional study.
      METHODS: Through state and provincial societies, members were queried as to
      cataract surgery practices during the previous 3 years as well as the specifics
      associated with each case of wound burn, if any, encountered during that period.
      RESULTS: Eight hundred forty-two cataract surgeons reported on 920,095 surgeries
      and 341 wound burns (raw incidence 0.037%). After a multivariate analysis, the
      wound burn incidence was significantly inversely associated with the surgeon's
      surgical volume (45% decrease per doubling of volume; 95% confidence interval,
      38%-55%; P<.001), the surgical approach (P<.001), and the ophthalmic
      viscosurgical device (OVD) used (P=.004). Machine or ultrasound modality used,
      region of the U.S. or Canada, and incision size were not related to wound burn.
      CONCLUSION: Phacoemulsification-induced wound burn can be reduced by experience,
      by the approach used in nucleus disassembly, by choice of OVD, and most
      important, by not using ultrasound when the anterior chamber is filled with OVD.

PMID- 22133552
TI  - Control of cell nucleus shapes via micropillar patterns.
AB  - We herein report a material technique to control the shapes of cell nuclei by the
      design of the microtopography of substrates to which the cells adhere. Poly(D,L
      lactide-co-glycolide) (PLGA) micropillars or micropits of a series of height or
      depth were fabricated, and some surprising self deformation of the nuclei of bone
      marrow stromal cells (BMSCs) was found in the case of micropillars with a
      sufficient height. Despite severe nucleus deformation, BMSCs kept the ability of
      proliferation and differentiation. We further demonstrated that the shapes of
      cell nuclei could be regulated by the appropriate micropillar patterns. Besides
      circular and elliptoid shapes, some unusual nucleus shapes of BMSCs have been
      achieved, such as square, cross, dumbbell, and asymmetric sphere-protrusion.

PMID- 22133551
TI  - The brain targeting mechanism of Angiopep-conjugated poly(ethylene glycol)-co
      poly(epsilon-caprolactone) nanoparticles.
AB  - In order to evaluate the potential and mechanism of Angiopep-conjugated
      poly(ethylene glycol)-co-poly(epsilon-caprolactone)nanoparticles (ANG-PEG-NP) as
      brain targeting drug delivery system, Rhodamine B isothiocyanate (RBITC) was used
      as a fluorescent probe molecule to label ANG-PEG-NP through covalent bonding. The
      brain transcytosis across the blood-brain barrier (BBB) and brain delivery in
      mice of RBITC labeled ANG-PEG-NP were investigated in this paper. Results showed
      that ANG-PEG-NP enhanced significantly the uptake by BCECs compared with that of
      PEG-NP through caveolae- and clathrin-mediated endocytosis, involving a time
      dependent, concentration-dependent and energy-dependent mode. The transport of
      ANG-PEG-NP across the in vitro BBB model was significantly increased than that of
      PEG-NP. After injection a dose of 100 mg/kg RBITC labeled ANG-PEG-NP or PEG-NP in
      mouse caudal vein, the brain coronal section showed a higher accumulation of ANG
      PEG-NP in the cortical layer, lateral ventricle, third ventricles and hippocampus
      than that of PEG-NP. By using an excess of free LRP ligand (Angiopep-2 and/or
      Aprotinin) as a specific receptor inhibitor, it was evidenced that the uptake by
      BCECs in vitro, transport across in vitro BBB model and penetration into brain
      tissue in vivo of RBITC labeled ANG-PEG-NP could be inhibited significantly,
      which demonstrated the brain targeting mechanism of Angiopep-conjugated
      poly(ethylene glycol)-co-poly(epsilon-caprolactone)nanoparticles might be a LRP
      receptor mediated transcytosis process. Understanding these issues is important
      for the future development of ANG-PEG-NP as a brain targeting drug delivery
      system for neurodegenerative disorders including glioma and Alzheimer's disease.

PMID- 22133553
TI  - Positioning and integrating medication therapy management.
AB  - OBJECTIVES: To summarize findings from medication therapy management (MTM)
      "environmental scans" conducted from 2007 through 2010, interpret findings from
      the environmental scans using insights gained from the Future of MTM Roundtable
      convened in October 2010, and propose ideas for future positioning and
      integrating of MTM programs in the U.S. health care system. METHODS: Data for the
      environmental scans were collected from purposive samples of MTM pharmacist
      providers and MTM payers throughout the United States using self-administered
      online surveys in 2007, 2008, 2009, and 2010. RESULTS: Based on the findings, it
      appears that MTM is becoming more developed and that some aspects of MTM have
      become established within the organizations that are providing and paying for
      these programs. However, the findings also revealed that a need exists to better
      integrate MTM between organizations and patients serviced (business-to-consumer
      relationships), between partnering organizations (business-to-business
      relationships), and between collaborating practitioners (peer-to-peer
      relationships). CONCLUSION: The findings suggest that a "channel of distribution"
      is emerging in which organizational relationships and cost efficiencies will be
      important considerations in the near term. We propose that applying (1) customer
      portfolio management and (2) transaction cost economics would help improve
      positioning and integrating MTM into the U.S. health care system.

PMID- 22133554
TI  - Sharing science: enabling global access to the scientific literature.

PMID- 22133555
TI  - The investigation and treatment of secondary anaemia.
AB  - Secondary anaemia or the anaemia of chronic disease (ACD) is the commonest form
      of anaemia in hospitalised patients and the second most prevalent anaemia
      worldwide after iron deficiency. It is characterised by defective iron
      incorporation in erythropoiesis, an impaired response to erythropoietin, a
      decrease in erythropoietin production and cytokine induced shortening of red cell
      survival. For many patients with ACD the cause is apparent but for many others
      the underlying disease needs to be determined and such patients are often
      referred to haematologists for investigation. The search for the cause can be a
      fascinating exercise in good history taking, examination skills and performing
      and interpreting appropriate investigations. This review covers the pathogenesis
      and causes of ACD and then discusses the clinical and laboratory investigation of
      a patient with suspected ACD. Finally, the management of a patient with ACD is
      discussed including erythropoiesis stimulating agents (ESAs), intravenous iron
      and future therapies.

PMID- 22133556
TI  - Comparison of in vivo bioluminescence imaging and lavage biomarkers to assess
      pulmonary inflammation.
AB  - Gram-negative bacterial endotoxin triggers innate immunity via TLR-4 and NF-kB
      signal activation. The aim of this study was to evaluate the use of transgenic
      mice expressing luciferase as a marker of NF-kB activation for exploring innate
      immune responses to pulmonary endotoxin exposure over time thus obviating the
      need for serial necropsies. Transgenic rNF-kB-Luc BALB/c mice were exposed to two
      different types of endotoxin (Neisseria meningitidis lipooligosaccharide, and
      Escherichia coli lipopolysaccharide) at multiple doses by nasal instillation.
      Bioluminescence was quantified in vivo at five time points in three separate
      experiments. In the fourth experiment lungs were imaged ex vivo 8h post exposure
      and tissue was analyzed for luciferase activity. Non-transgenic BALB/c mice were
      similarly exposed to lipooligosaccharide and bronchoalveolar lavage was assessed
      for neutrophil recruitment and IL-6. Non-transgenic BALB/c mice exhibited highly
      significant increases of IL-6 and neutrophils in bronchoalveolar lavage 4h after
      the exposure to instilled doses as low as 30EU/mouse. In contrast, luciferase
      imaging of NF-kB signal activation in vivo in transgenic rNF-kB-Luc mice did not
      show significant changes over time or over doses from 30EU to 300,000EU/mouse of
      nasally-instilled endotoxin. Ex vivo lung imaging 8h after endotoxin exposure to
      3000EU demonstrated a strong signal. An intravenous LPS dose of 300,000EU/mouse
      produced a measurable luminescence signal in vivo. This non-terminal assessment
      method is useful only with extremely high doses of endotoxin that induce systemic
      injury and cannot be applied to research of occupational and environmental
      exposures at relevant levels of endotoxin.

PMID- 22133558
TI  - The addictive hypothesis of suicidal behavior.

PMID- 22133557
TI  - Are gamma-secretase and its associated Alzheimer's disease gamma problems?
AB  - Presenilins (PS1 and PS2) and the amyloid-beta precursor protein (AbetaPP) are
      the only known proteins as causing monogenic Alzheimer's disease. AbetaPP is not
      the unique substrate of the gamma-secretase complex. Presenilins are also
      implicated in the processing of Notch, an important developmental protein, which
      is thought to compete directly with AbetaPP for cleavage by gamma-secretase. In
      the context of cleavages in alpha, beta and gamma and with the recent three
      dimensional models of gamma-secretase complex, a kinetic study of the sequential
      proteolysis of AbetaPP prompts us to think the possible existence of two entrance
      sites for substrate with only one exit site, a configuration depicting a
      lowercase gamma letter. The quantitative distribution of the cleavage products by
      the gamma-secretase, mainly Abeta(40), Abeta(42) and Abeta(43), could be
      explained in the context of this hypothesis. Based on published results in the
      literature and the analyses of AbetaPP C99 fragment, highly abundant in Down's
      syndrome patients, we propose that beta- and gamma-secretases can function as a
      supra-enzyme complex where AbetaPP substrate might be attached to the gamma
      secretase complex before beta cleavage takes place. Different studies point that
      a small peptide sequence, showing homology in presenilins and AbetaPP, plays a
      pivotal role and that minor alterations in the sequence of AbetaPP protein limit
      the formation of C99 and also of Abeta(40) and Abeta(42). The model proposed
      could be of importance in future studies aimed at understanding the specific
      events involved in course of Alzheimer disease pathophysiology and also at
      studying of formation/deterioration of memory.

PMID- 22133559
TI  - New treatment strategy for granulomatous epulis: intralesional injection of
      propranolol.
AB  - Epulis is a relapsable lesion in gingiva without specific treatment for its
      unexplained pathogenesis. Nowadays, surgical excision is the most popular method
      of treatment. To prevent recurrence, it is necessary to resect diseased tissues
      thoroughly, and even to remove the involved teeth. However, this may cause
      functional and cosmetic deformities. Therefore, it is urgent to find a new
      therapy without severe side effects. Infantile hemangioma is a common benign
      pediatric tumor which shares many features with epulis, such as rich vascularity,
      high incidence of female patients, high hormone level and similar treatments. A
      recent study showed that propranolol, a beta adrenergic receptor (beta-AR)
      antagonist, was effective as treatment for infantile hemangioma. Our preliminary
      work showed that mRNA and protein levels of beta2-AR were higher in epulis than
      in adjacent tissue. Therefore, we hypothesize that intralesional injection of
      propranolol may be useful as epulis treatment. Further work need to be done to
      confirm the safety and therapeutic effect of the treatment. After that, this
      specific beta2-AR antagonist may be the first choice for epulis treatment.

PMID- 22133560
TI  - Temperature-pressure-induced solid-solid <100> to <110> reorientation in FCC
      metallic nanowire: a molecular dynamic study.
AB  - Atomistic simulation of initial <100> oriented FCC Cu nanowires shows a novel
      coupled temperature-pressure dependent reorientation from <100> to <110> phase. A
      temperature-pressure-induced solid-solid <100> to <110> reorientation diagram is
      generated for Cu nanowire with varying cross-sectional sizes. A critical pressure
      is reported for Cu nanowires with varying cross-sectional sizes, above which an
      initial <100> oriented nanowire shows temperature independent reorientation into
      the <110> phase. The effect of surface stresses on the <100> to <110>
      reorientation is also studied. The results indicate that above a critical cross
      sectional size for a given temperature-pressure, <100> to <110> reorientation is
      not possible. It is also reported here that for a given applied pressure, an
      increase in temperature is required for the <100> to <110> reorientation with
      increasing cross-sectional size of the nanowire. The temperature-pressure-induced
      solid-solid <100> to <110> reorientation diagram reported in the present paper
      could further be used as guidelines for controlling the reorientations/shape
      memory in nano-scale applications of FCC metallic nanowires.

PMID- 22133561
TI  - In your place: neuropsychological evidence for altercentric remapping in embodied
      perspective taking.
AB  - Humans are able to mentally adopt the spatial perspective of others and represent
      the visual world from their point of view. Here, we present neuropsychological
      evidence that information inaccessible from an egocentric perspective can be
      accessed from the perspective of another person. Patients affected by left
      neglect were asked to describe arrays of objects from their own egocentric
      perspective, from an opposite perspective (disembodied perspective taking), and
      from the point of view of another person actually seated in front of them
      (embodied perspective taking). Although disembodied perspective-taking
      ameliorated neglect severity, there was an even stronger positive effect of
      embodied perspective-taking: items presented on the left and neglected when
      reported from the egocentric perspective were instead recovered when patients
      assumed the perspective of the other. These findings suggest that perspective
      taking entails an altercentric remapping of space, i.e. remapping of objects and
      locations coded with reference to the other person's body.

PMID- 22133562
TI  - High responsivity to threat during the initial stage of perception in repression:
      a 3 T fMRI study.
AB  - Repression designates coping strategies such as avoidance, or denial that aim to
      shield the organism from threatening stimuli. Derakshan et al. have proposed the
      vigilance-avoidance theory of repressive coping. It is assumed that repressors
      have an initial rapid vigilant response triggering physiological responses to
      threat stimuli. In the following second stage repressors manifest avoidant
      cognitive biases. Functional magnetic resonance imaging at 3T was used to study
      neural correlates of repressive coping during the first stages of perception of
      threat. Pictures of human faces bearing fearful, angry, happy and neutral
      expressions were briefly presented masked by neutral faces. Forty study
      participants (20 repressive and 20 sensitizing individuals) were selected from a
      sample of 150 female students on the basis of their scores on the Mainz Coping
      Inventory. Repressors exhibited stronger neural activation than sensitizers
      primarily in response to masked threatening faces (vs neutral baseline) in the
      frontal, parietal and temporal cortex as well as in the cingulate gyrus, basal
      ganglia and insula. There was no brain region in which sensitizers showed
      increased activation to emotion expression compared to repressors. The present
      results are in line with the vigilance-avoidance theory which predicts heightened
      automatic responsivity to threatening stimuli in repression.

PMID- 22133563
TI  - Exploring the milk-clotting properties of a plant coagulant from the berries of
      S. elaeagnifolium var. Cavanilles.
AB  - Solanum elaeagnifolium (trompillo or silverleaf nightshade) is an endemic plant
      from the northeast of Mexico and southwest of United States. This plant is
      considered as a weed with negative impact on agriculture and livestock
      production. Nevertheless, in some places of Chihuahua, Mexico, the berries of
      this plant have been used for decades in the manufacture of artisanal filata-type
      asadero cheese. The milk-clotting enzyme of S. elaeagnifolium has been scarcely
      studied; for this reason, the aim of this work was to explore some properties of
      this plant coagulant. Protein extracts (PEs) from ripe berries of S.
      elaeagnifolium were characterized by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and assessed for milk-clotting activity. In addition,
      milk gels and miniature fresh-type cheeses manufactured with the plant coagulant
      were analyzed for their texture properties. The PE from the berries of S.
      elaeagnifolium contained 8 proteins with molecular weights from 22 to 62 kDa.
      Some bands observed in the PE had similar molecular weights as reported for
      aspartic proteinases such as chymosin. The extracts from the berries of S.
      elaeagnifolium had lower milk-cloting activities than observed with rennin or
      chymosin, but this plant coagulant produced firm gels under acidic conditions.
      The mini-cheeses manufactured with this coagulant were softer than cheeses
      manufactured with rennin or chymosin. For this reason, the coagulant from the
      ripe berries of S. elaeagnifolium could be suitable not only for the manufacture
      of filata-type cheeses but also for the manufacture of soft cheeses such as cream
      cheese. PRACTICAL APPLICATION: Silverleaf nightshade (trompillo) is a plant that
      grows in northern Mexico and the southwestern United States. This plant is
      considered a weed with negative impact on agriculture and livestock production.
      However, the ripe berries of this plant have been used by ancient Pima Indians as
      a substitute of rennin in making cheese. In this work, it was observed that this
      plant coagulant had lower activity and produced softer cheeses than did rennin or
      chymosin. For this reason, the coagulant from berries of S. elaeagnifolium could
      be used for the manufacture of soft cheeses such as cream cheese.

PMID- 22133564
TI  - Safety assessment of Lactobacillus plantarum JDM1 based on the complete genome.
AB  - We performed a comprehensive safety assessment of a probiotic based on the whole
      genome sequence and corresponding phenotypes. This was performed on Lactobacillus
      plantarum JDM1, a widely used commercial probiotic strain in China. The minimal
      inhibitory concentrations (MICs) of sixteen antibiotics and the biogenic amine
      production of JDM1 were tested to supplement a traditional oral toxicity test. In
      total, fifty-one antibiotic resistance-associated genes, one hundred twenty-six
      virulence-associated genes, and twenty-three adverse metabolism-associated genes
      were found in JDM1. However, there were no toxin or hemolysin encoding genes, and
      safety-associated genes were rarely transferable. This approach can be
      generalized to provide a deep safety investigation of novel probiotic strains and
      greatly reveal the potential danger determinants and their molecular mechanisms.
      However, this kind of analysis reveals the theoretical maximum risk level as not
      all genes are efficient depending on environmental conditions.

PMID- 22133565
TI  - Source attribution, prevalence and enumeration of Campylobacter spp. from retail
      liver.
AB  - Campylobacter prevalence from retail liver (chicken, cattle, pig and sheep) was
      found to be 81%, 69%, 79% and 78% respectively. Molecular source attribution
      demonstrated that strains from chicken liver were most similar to those found
      commonly in humans. This provides further evidence of liver being a probable
      source of human infection.

PMID- 22133566
TI  - Transcription profiling of sparkling wine second fermentation.
AB  - There is a specific set of stress factors that yeast cells must overcome under
      second fermentation conditions, during the production of sparkling wines by the
      traditional (Champenoise) method. Some of them are the same as those of the
      primary fermentation of still wines, although perhaps with a different intensity
      (high ethanol concentration, low pH, nitrogen starvation) while others are more
      specific to second fermentation (low temperature, CO(2) overpressure). The
      transcription profile of Saccharomyces cerevisiae during primary wine
      fermentation has been studied by several research groups, but this is the first
      report on yeast transcriptome under second fermentation conditions. Our results
      indicate that the main pathways affected by these particular conditions are
      related to aerobic respiration, but genes related to vacuolar and peroxisomal
      functions were also highlighted in this study. A parallelism between the
      transcription profile of wine yeast during primary and second fermentation is
      appreciated, with ethanol appearing as the main factor driving gene transcription
      during second fermentation. Low temperature seems to also influence yeast
      transcription profile under these particular winemaking conditions.

PMID- 22133568
TI  - It's not all in the cilium, but on the road to it: genetic interaction network in
      polycystic kidney and liver diseases and how trafficking and quality control
      matter.
AB  - Autosomal dominant polycystic liver disease results from mutations in PRKCSH or
      SEC63. The respective gene products, glucosidase IIb and SEC63p, function in
      protein translocation and quality control pathways in the endoplasmic reticulum.
      Here we show that glucosidase IIb and Sec63p are required in mice for adequate
      expression of a functional complex of the polycystic kidney disease gene
      products, polycystin-1 and polycystin-2. We find that polycystin-1 is the rate
      limiting component of this complex and that there is a dose-response relationship
      between cystic dilation and levels of functional polycystin-1 following mutation
      of Prkcsh or Sec63.Reduced expression of polycystin-1 also serves to sensitize
      the kidney to cyst formation resulting from mutations in Pkhd1, the recessive
      polycystic kidney disease gene. Finally, we show that proteasome inhibition
      increases steady-state levels of polycystin-1 in cells lacking glucosidase IIb
      and that treatment with a proteasome inhibit or reduces cystic disease in
      orthologous gene models of human autosomal dominant polycystic liver.

PMID- 22133569
TI  - Synergism between baltergin metalloproteinase and Ba SPII RP4 PLA2 from Bothrops
      alternatus venom on skeletal muscle (C2C12) cells.
AB  - Acute muscle damage, myonecrosis, is one of the main characteristics of
      envenoming by Bothrops genus. In this in vitro study we investigated the role of
      a metalloproteinase (baltergin) and an acidic phospholipase A2 (Ba SPII RP4) in
      the cytotoxicity exhibited by Bothrops alternatus venom. Baltergin
      metalloproteinase purified from the venom exerted a toxic effect on C2C12
      myoblast cells (CC50: 583.34 MUg/mL) which involved morphological alterations
      compatible with apoptosis/anoikis. On the contrary, the most abundant PLA2
      isolated from this venom did not exhibit cytotoxicity at times and doses tested.
      However, when myoblasts were treated with both enzymes together, synergic
      activity was demonstrated. Neutralization of the venom with specific antibodies
      (IgG anti-baltergin and IgG anti-PLA2) confirmed this synergism.

PMID- 22133570
TI  - Myotoxicity and nephrotoxicity by Micrurus venoms in experimental envenomation.
AB  - Micrurus venoms are essentially neurotoxic but other activities, such as
      myotoxicity, may be apparent under experimental conditions. Although this
      myotoxicity has been occasionally reported, there are no studies addressing it
      systematically across the genus, particularly in its relationship to other
      systemic manifestations such as renal impairment. The lethal potency of Micrurus
      fulvius, Micrurus nigrocinctus, Micrurus surinamensis, Micrurus altirostris,
      Micrurus balyocoriphus and Micrurus pyrrhocryptus venoms determined by us were in
      the range described for the genus and all venoms exhibited phospholipase
      activity, albeit at significantly different levels. Intramuscular venom injection
      caused variable local inflammation-edema; myotoxicity (as determined by plasma
      creatine kinase levels and histopathology) was apparent only in those venoms with
      highest phospholipase activity, namely M. fulvius, M. nigrocinctus and M.
      pyrrhocryptus. Kidneys of animals injected with these strongly myotoxic venoms
      showed lesions consisting in extensive tubular necrosis with nuclear
      fragmentation, destruction of the brush border, rupture of basal membrane and
      epithelial exfoliation of tubular cells, granular cast and thickening of tubules.
      The histological characteristics of the lesions suggest an important role for
      indirect glomerular damage by myoglobin deposits. Phospholipase and myotoxic
      activities did not correlate significantly to the lethal potency; renal lesions
      were, however, evident only in those venoms that caused extensive muscular
      damage. Although kidney lesions have not been described in clinical cases of
      Micrurus envenomation, the potential for nephrotoxicity of some of these venoms
      should be considered in the overall toxicological picture, at least in
      experimental conditions.

PMID- 22133571
TI  - Tetraploidy in BRCA2 breast tumours.
AB  - Tetraploidy and aneuploidy can be caused by cell division errors and are
      frequently observed in many human carcinomas. We have recently reported delayed
      cytokinesis in primary human fibroblasts from BRCA2 mutation carriers, implying a
      function for the BRCA2 tumour suppressor in completion of cell division. Here, we
      address ploidy aberrations in breast tumours derived from BRCA2 germline mutation
      carriers. Ploidy aberrations were evaluated from flow cytometry histograms on
      selected breast tumour samples (n=236), previously screened for local BRCA
      mutations. The ploidy between BRCA2-mutated (n=71) and matched sporadic (n=165)
      cancers was compared. Differences in ploidy distribution were examined with
      respect to molecular tumour subtypes, previously defined by immunohistochemistry
      on tissue microarray sections. Tetraploidy was significantly 3 times more common
      in BRCA2 breast cancers than sporadic. However, no differences were found in the
      overall ploidy distribution between BRCA2-mutation carriers and non-carriers. In
      BRCA2 cancers, tetraploidy was associated with luminal characteristics. The
      increased frequency of tetraploidy in BRCA2 associated cancers may be linked to
      cell division errors, particularly cytokinesis. Additionally, tetraploidy emerges
      predominantly in BRCA2 breast cancers displaying luminal rather than triple
      negative phenotypes.

PMID- 22133572
TI  - Response prediction in metastasised colorectal cancer using intratumoural
      thymidylate synthase: results of a randomised multicentre trial.
AB  - BACKGROUND: Molecular markers to predict response to 5-fluorouracil (FU)-based
      treatment of recurrent or metastasised colorectal cancer (mCRC) are not
      established. The aim of this trial was to determine the value of thymidylate
      synthase (TS), a key enzyme of DNA synthesis and target of 5-FU, to predict
      response to chemotherapy of mCRC. METHODS: Tumour tissue was obtained from 168
      patients with mCRC for relative thymidylate synthase (TS) mRNA quantitation.
      Patients were randomised to receive either 5-FU/folinic acid (FA, FUFA) alone or
      in combination with irinotecan 5-fluorouracil/folinic acid and irinotecan
      (FOLFIRI) stratified by TS (low versus high). Primary end-point was overall
      response to first-line treatment among TS high patients. All parties, except for
      the randomisation centre, were blinded for TS status. RESULTS: Biopsies (n=168)
      were taken without complications. TS levels were available for 147 patients
      (87.5%). Analysing response to FUFA and FOLFIRI in the per protocol set (n=119)
      after un-blinding TS in the data base revealed a trend to better overall response
      to FOLFIRI (9/19, 47%) in TS high compared to FUFA (5/23, 22%, p=0.077). In
      patients with biopsies taken from liver lesions (n=91) overall response to
      FOLFIRI and FUFA in TS high was 53% (9/17) and 18% (3/17), respectively
      (p=0.035). In patients with low TS, no remarkable difference in overall response
      to FOLFIRI and FUFA was observed. CONCLUSIONS: Taking a pre-treatment biopsy is a
      safe and feasible procedure in mCRC. After validation of our data in a larger
      group TS determination may have the potential to better help direct systemic
      treatment in patients with primarily non-resectable mCRC.

PMID- 22133573
TI  - Is the combination of chromogranin A and pancreatic polypeptide serum
      determinations of interest in the diagnosis and follow-up of gastro-entero
      pancreatic neuroendocrine tumours?
AB  - INTRODUCTION: Chromogranin A (CgA) is the principal tumour marker for
      gastroenteropancreatic neuroendocrine tumours (GEPNET). Combining serum CgA and
      pancreatic polypeptide (PP) levels may increase the sensitivity of tumour markers
      in the diagnosis of GEPNET. OBJECTIVES: (1) To evaluate the sensitivity of PP and
      CgA in GEPNET. (2) To compare changes in serum CgA and PP levels with the
      morphological evolution of the tumours. PATIENTS AND METHODS: Sixty-six
      pancreatic and 49 gastrointestinal NET, with at least one serum determination of
      CgA and PP at the same time were retrieved from an institutional data base.
      Secondly, the variations in serum CgA or PP at successive determinations were
      compared to Response Evaluation Criteria in Solid Tumours (RECIST) criteria in 57
      patients (112 follow-up visits) with high serum CgA levels and in 21 patients (37
      follow-up visits) with high serum PP levels. RESULTS: Among the 115 patients
      included in the study group, an increase in serum CgA (normal <98 MUg/L) or PP
      (normal <100 pmol/L) was found in respectively 79 (69%) and 36 (31%) cases. Seven
      patients had normal CgA and elevated PP levels. Both markers were significantly
      more elevated in metastatic disease (74% versus 51% for CgA and 37% versus 18%
      for PP). The concordance rates between serum markers and RECIST criteria were 51%
      for CgA and 54% for PP. CONCLUSIONS: Serum PP determination identify few false
      negative results of serum CgA determination in GEPNET. Our study does not
      validate the use of CgA or PP as surrogate markers for detecting changes in
      tumour burden.

PMID- 22133574
TI  - Pretreatment with oral contraceptive pills does not influence the pregnancy rate
      in the long leuprolide acetate protocol.
AB  - BACKGROUND: To analyze the influence of oral contraceptive pill (OCP)
      pretreatment in intracytoplasmic sperm injection cycles among normoresponders in
      whom leuprolide acetate is preferred for that kind of gonadotropin-releasing
      hormone agonist. METHODS: Between March 2001 and January 2010, a total of 821
      cycles were pretreated with OCP in luteal-long leuprolide acetate in the IVF
      Center, Faculty of Medicine, University of Hacettepe. Of these, a total of 169
      consecutive patients were selected for the final analyses according to the
      selection criteria (OCP group) and compared with 349 age-matched controls
      (Control group). The normoresponders were defined by the presence of 6-15 antral
      follicles in both ovaries. RESULTS: Female age, body mass index, duration of
      infertility and antral follicle count were similar among both groups. Although
      the total dose of FSH used and duration of stimulation were similar, the maximal
      serum estradiol concentrations were higher in the OCP group than in the Control
      group (2,630.3 +/- 1,568.0 vs. 2,166.5 +/- 1,259.7 pg/ml, p = 0.001). The mean
      numbers of metaphase-II oocytes were 11.0 +/- 6.2 versus 9.4 +/- 5.2 in the OCP
      and Control groups, respectively (p = 0.004). The mean number of available day 3
      embryos having >=7 blastomeres was also higher in the OCP group (4.4 +/- 3.3 vs.
      3.5 +/- 3.1, p = 0.013). However, the embryo transfer cancellation rate was noted
      to be higher in the OCP group, which is mainly due to fertilization failure and
      arrest during embryogenesis (6.5 vs. 2.9%, p = 0.049). The clinical pregnancy
      (36.7 vs. 38.3%) and implantation rates (21.8 vs. 20.6%) were comparable.
      CONCLUSION: These findings suggest that although pretreatment with an OCP might
      exaggerate ovarian response, the pregnancy rate does not fluctuate in leuprolide
      acetate cycles among normoresponders.

PMID- 22133575
TI  - A fast multichannel Martin-Puplett interferometer for electron cyclotron emission
      measurements on JET.
AB  - A Martin Puplett interferometer for electron cyclotron emission (ECE)
      measurements from JET tokamak plasmas was extended to multichannel operation for
      simultaneous radial and oblique ECE measurements. This paper describes the new
      optics and the instrument's performance.

PMID- 22133576
TI  - Influence of non-alcoholic fatty liver disease on the prognosis in patients with
      colorectal cancer.
AB  - BACKGROUND/AIM: Non-alcoholic fatty liver disease (NAFLD) is associated with
      multiple adenomatous polyps and advanced neoplasm. This study aims to investigate
      the influence of NAFLD on the tumor characteristics and prognosis in patients
      with colorectal cancer (CRC). METHODS: We analyzed 227 patients who were first
      diagnosed with CRC and underwent abdominal ultrasonography within six months
      prior to diagnosis at Samsung Medical Center between 2000 and 2005. RESULTS: Of
      the study population, 26.0% were diagnosed with NAFLD. Upon baseline comparison,
      CRC patients with NAFLD had higher BMI and ALT values than CRC patients without
      NAFLD (25.3 +/- 2.7 vs. 22.6 +/- 3.0, P=0.000 and 26.6 +/- 17.4 vs. 21.2 +/-
      14.0, P=0.018, respectively). Additionally, CRC patients with NAFLD were
      diagnosed earlier than CRC patients without NAFLD (P=0.004). However, there were
      no significant differences between two groups with regard to location and
      differentiation of tumors, CEA or numbers of synchronous adenoma and advanced
      adenoma. The cumulative 1-, 3-, and 5-year survival rates in CRC patients with
      NAFLD were 98.3%, 89.8%, and 86.4%, respectively, which were higher but
      statistically not significant than 90.4%, 79.6%, and 74.8%, respectively, in CRC
      patients without NAFLD (P=0.079). During follow-up, freedom from recurrence was
      similarly observed in CRC patients with and without NAFLD (89.8% and 87.3%,
      respectively, P=0.614). CONCLUSIONS: The results of this study suggest that the
      presence of NAFLD does not influence on the prognosis in CRC patients, especially
      with respect to disease recurrence during follow-up.

PMID- 22133577
TI  - Ionic aggregate structure in ionomer melts: effect of molecular architecture on
      aggregates and the ionomer peak.
AB  - We perform a comprehensive set of coarse-grained molecular dynamics simulations
      of ionomer melts with varying polymer architectures and compare the results to
      experiments in order to understand ionic aggregation on a molecular level. The
      model ionomers contain periodically or randomly spaced charged beads, placed
      either within or pendant to the polymer backbone, with the counterions treated
      explicitly. The ionic aggregate structure was determined as a function of the
      spacing of charged beads and also depends on whether the charged beads are in the
      polymer backbone or pendant to the backbone. The low wavevector ionomer peak in
      the counterion scattering is observed for all systems, and it is sharpest for
      ionomers with periodically spaced pendant charged beads with a large spacing
      between charged beads. Changing to a random or a shorter spacing moves the peak
      to lower wavevector. We present new experimental X-ray scattering data on Na(+)
      neutralized poly(ethylene-co-acrylic acid) ionomers that show the same two trends
      in the ionomer peak, for similarly structured ionomers. The order within and
      between aggregates, and how this relates to various models used to fit the
      ionomer peak, is quantified and discussed.

PMID- 22133578
TI  - The contribution of apoptosis-inducing factor (AIF) to villous trophoblast
      differentiation.
AB  - Apoptosis is postulated to be a delayed but important part of the differentiation
      of placental villous cytotrophoblasts (CT) into functional syncytiotrophoblast
      (ST). This hypothesis is based on the observation that the externalization of
      phosphatidylserine and the activation of caspase 8 are required for trophoblast
      differentiation. In contradiction to this hypothesis we have previously found
      that differentiation occurs in the presence of both broad spectrum and caspase 8
      specific inhibitors. Apoptosis-inducing factor (AIF) is a mitochondria-associated
      protein which is known to translocate to the nucleus and induce caspase
      independent nuclear condensation, phosphatidylserine externalization and cell
      death. Thus AIF nuclear translocation may result in the apoptotic-like features
      associated with trophoblast differentiation and may be an obligatory event for
      differentiation to proceed. AIF translocation was assessed in isolated primary
      trophoblasts by optical section microscopy of antibody stained cells. We found
      AIF to be strongly expressed in the villous trophoblast and that small amounts of
      AIF were localized to the nucleus of the cells. Significantly, inhibitors of AIF
      translocation (calpeptin and zFA-fmk) blocked translocation but not
      differentiation of the cells. We conclude that AIF translocation is not involved
      in CT differentiation in isolated cell culture.

PMID- 22133579
TI  - Insights for treatment in Tourette syndrome from fMRI.
AB  - In a recent American Journal of Psychiatry article, Wang and colleagues used
      functional MRI (fMRI) to examine cortico-striatal-thalamo-cortical circuitry in
      Tourette syndrome (TS), advancing the field's investigation of circuit level
      dysfunction in vivo in individuals with TS. Their results provide insight for
      interrogating neural mechanisms underlying different treatment methods.

PMID- 22133580
TI  - Cognitive function predicts weight loss after bariatric surgery.
AB  - BACKGROUND: Clinically significant cognitive impairment is found in a subset of
      patients undergoing bariatric surgery. These difficulties could contribute to a
      reduced adherence to postoperative lifestyle changes and decreased weight loss.
      The present study is the first to prospectively examine the independent
      contribution of cognitive function to weight loss after bariatric surgery.
      Executive function/attention and verbal memory at baseline were expected to
      negatively predict the percentage of excess weight loss (%EWL) and body mass
      index (BMI) at follow-up. Three sites of the Longitudinal Assessment of Bariatric
      Surgery parent project were used: Columbia (New York, NY), Cornell (Princeton,
      NJ), and the Neuropsychiatric Research Institute (Fargo, ND). METHODS: A total of
      84 individuals enrolled in the Longitudinal Assessment of Bariatric Surgery
      project undergoing bariatric surgery completed a cognitive evaluation at
      baseline. The BMI and %EWL were calculated at the 12-week and 12-month
      postoperative follow-up visits. RESULTS: Clinical impairment in task performance
      was most prominent in tasks associated with verbal recall and recognition (14.3
      15.5% of the sample) and perseverative errors (15.5%). After accounting for
      demographic and medical variables, the baseline test results of
      attention/executive function and memory predicted the BMI and %EWL at 12 months
      but not at 12 weeks. CONCLUSIONS: These results have demonstrated that baseline
      cognition predicts for greater %EWL and lower BMI 12 months after bariatric
      surgery. Additional work is needed to clarify the degree to which cognition
      contributes to adherence and the potential mediation of cognition on the
      relationship between adherence and weight loss in this group.

PMID- 22133581
TI  - More lack in the world: the complex connection between undernutrition and climate
      change.

PMID- 22133582
TI  - Single crystal study of the heavy-fermion antiferromagnet CePt2In7.
AB  - We report the synthesis, structure, and physical properties of single crystals of
      CePt(2)In(7). Single crystal x-ray diffraction analysis confirms the tetragonal
      I4/mmm structure of CePt(2)In(7) with unit cell parameters a = 4.5886(6) A, c =
      21.530(6) A and V = 453.32(14) A(3). The magnetic susceptibility, heat capacity,
      Hall effect and electrical resistivity measurements are all consistent with
      CePt(2)In(7) undergoing an antiferromagnetic order transition at T(N) = 5.5 K,
      which is field independent up to 9 T. Above T(N), the Sommerfeld coefficient of
      specific heat is gamma ~ 300 mJ mol(-1) K(-2), which is characteristic of an
      enhanced effective mass of itinerant charge carriers. The electrical resistivity
      is typical of heavy-fermion behavior and gives a residual resistivity rho(0) ~
      0.2 uOmega cm, indicating good crystal quality. CePt(2)In(7) also shows moderate
      anisotropy of the physical properties that is comparable to structurally related
      CeMIn(5) (M = Co, Rh, Ir) heavy-fermion superconductors.

PMID- 22133583
TI  - The politics of place(ment): problematising the provision of hepatitis C
      treatment within opiate substitution clinics.
AB  - The hepatitis C virus (HCV) epidemic is a significant public health challenge in
      Australia. Current initiatives to expand access to HCV treatment focus on opiate
      substitution therapy (OST) settings where the prevalence of hepatitis C among
      clients is high. In Australia, the provision of OST for many clients is via large
      clinics, with an estimated median of 150 clients per service. Conceptually
      informed by the work of Michel Foucault, our analysis of the proposed integrated
      treatment model focuses on the critical but overlooked question of organisational
      culture and power operating within OST. We argue that the specific context of OST
      not merely reflects but actively participates in the political economy of social
      exclusion via which the socio-spatial segregation and stigmatisation of the
      service user as 'drug user' is enacted. This paper analyses data collected from
      two samples during 2008/9: OST clients living in New South Wales, Australia and a
      range of OST health professionals working in Australian settings. In total, 27
      interviews were conducted with current OST clients; 19 by phone and 8 face-to
      face. One focus group and 16 telephone interviews were conducted with OST health
      professionals. Our analysis of key themes emerging from the interview data
      suggests that the successful introduction of HCV treatment within the OST clinic
      is not a given. We are concerned that particular areas of tension, if not
      explicit contradiction, have been overlooked in current research and debates
      informing the proposed combination treatment model. We question the
      appropriateness of co-locating a notoriously arduous, exacting treatment (HCV)
      within the highly surveillant and regulatory environment of OST. While applauding
      the intention to improve access to HCV care and treatment for people who inject
      drugs we caution against a treatment model that risks further entrenching (socio
      spatial) stigmatisation amongst those already experiencing significant
      marginalisation.

PMID- 22133584
TI  - Willingness to use ADHD treatments: a mixed methods study of perceptions by
      adolescents, parents, health professionals and teachers.
AB  - Little is known about factors that influence willingness to engage in treatment
      for attention deficit/hyperactivity disorder (ADHD). From 2007 to 2008, in the
      context of a longitudinal study assessing ADHD detection and service use in the
      United States, we simultaneously elicited ADHD treatment perceptions from four
      stakeholder groups: adolescents, parents, health care professionals and teachers.
      We assessed their willingness to use ADHD interventions and views of potential
      undesirable effects of two pharmacological (short- and long-acting ADHD
      medications) and three psychosocial (ADHD education, behavior therapy, and
      counseling) treatments. In multiple regression analysis, willingness was found to
      be significantly related to respondent type (lower for adolescents than adults),
      feeling knowledgeable, and considering treatments acceptable and helpful, but not
      significantly associated with stigma/embarrassment, respondent race, gender and
      socioeconomic status. Because conceptual models of undesirable effects are
      underdeveloped, we used grounded theory method to analyze open-ended survey
      responses to the question: "What other undesirable effects are you concerned
      about?" We identified general negative treatment perceptions (dislike, burden,
      perceived ineffectiveness) and specific undesirable effect expectations
      (physiological and psychological side effects, stigma and future dependence on
      drugs or therapies) for pharmacological and psychosocial treatments. In summary,
      findings indicate significant discrepancies between teens' and adults'
      willingness to use common ADHD interventions, with low teen willingness for any
      treatments. Results highlight the need to develop better treatment engagement
      practices for adolescents with ADHD.

PMID- 22133585
TI  - Public opinion and support for government AIDS policies in sub-Saharan Africa.
AB  - Based on data from Afrobarometer's 2008-2009 public opinion surveys in 20 sub
      Saharan African states, this article examines the extent of support for
      government AIDS policies. While many international and nongovernmental
      organizations have criticized African governments for failing to implement
      comprehensive HIV/AIDS policies, survey data shows that citizens have generally
      positive assessments of their governments' responses. The findings demonstrate
      that support for a government's AIDS policies arises less from demographic
      characteristics and more from experiences with and perceptions of the
      government's capabilities. In particular, those in better economic circumstances
      and those who approve of the president's job performance show particularly strong
      support for their government's AIDS policies. This may suggest that leaders are
      exhibiting the political will necessary to implement holistic AIDS policies and
      receiving support for them, but it may also suggest respondents are not
      differentiating between support for the government as a whole and support for
      particular policy areas.

PMID- 22133586
TI  - Effect of an oxygen scavenger on the stability of preservative-free flour
      tortillas.
AB  - Along with purge and moisture control, oxygen scavenging is a prominent active
      packaging technology employed by many food processors. The objective of this
      study was to determine the effect of an oxygen scavenger system (OSS) on the
      shelf life of preservative-free tortillas stored at varying storage conditions.
      The shelf life of the tortillas was evaluated at accelerated storage (AS; 37 
      degrees C, 75% relative humidity [rh]), room temperature (RT; 22  degrees C, 57%
      rh), and refrigeration (R; 4  degrees C, 42% rh) conditions. The OSS consisted of
      a multilayer, coextruded bag paired with an oxygen scavenger sachet. A resealable
      bag made of low-density polyethylene/linear low-density polyethylene was used as
      a control. The diameter, thickness, CIELab color, water activity, pH, texture,
      and microbial growth within the sample tortillas were measured before and after
      exposure to the storage conditions. The results showed that the OSS had
      superiority when compared to the control. The weight and thickness under RT
      remained unchanged, while lightness was superior to the control under R
      conditions. Under AS, gradient remained constant, and force followed the same
      pattern under RT and R conditions. At the same time, microbial growth as measured
      by aerobic plate count and yeast and molds showed no changes under both AS and RT
      conditions. Future studies will investigate the effect of a faster acting oxygen
      scavenger on shelf life of this type of tortillas. PRACTICAL APPLICATION: The
      results of this study show promise for the use of oxygen scavenging technology in
      the packaging of natural and preservative-free tortillas.

PMID- 22133587
TI  - Effects of the roughage/concentrate ratio on the expression of angiogenic growth
      factors in adipose tissue of fattening Wagyu steers.
AB  - In this experiment, we studied the effects of the dietary roughage/concentrate
      ratio on the expression of the angiogenic growth factor (VEGF and FGF-2) and the
      adipogenic transcription factor (C/EBPbeta, C/EBPalpha, and PPARgamma) gene in
      the adipose tissues of Wagyu steers. Steers were fed a high-roughage diet (R
      group, 35% roughage and 65% concentrate on a TDN basis) or a high-concentrate
      diet (C group, 10% roughage and 90% concentrate) during the entire fattening
      period (from 10 to 30months of age) with the same amount of TDN intake between
      groups. In mesenteric and intermuscular adipocytes, the expression of the
      angiogenic growth factors was higher in the R group than in the C group. In
      contrast, the expression of adipogenic transcription factors in the subcutaneous
      and intramuscular adipocytes was higher in the C group than in the R group. These
      results indicate that the dietary roughage/concentrate ratio affects the fat
      depot-specific differences in the angiogenic and adipogenic gene expression
      pattern.

PMID- 22133588
TI  - Seasonal changes and muscle type effect on the nutritional quality of
      intramuscular fat in Mirandesa-PDO veal.
AB  - The influence of slaughter season and muscle type on the detailed fatty acid
      composition, including conjugated linoleic acid isomers, and contents of total
      cholesterol and lipid-soluble antioxidant vitamins (alpha-tocopherol and beta
      carotene) in Mirandesa-PDO veal was assessed. Mirandesa purebred calves (n=29)
      were raised in a traditional production semi-extensive system, slaughtered in
      late spring (June) or early autumn (October) and the longissimus lumborum and
      semitendinosus muscles were sampled for analysis. Although the lipid composition
      of PDO veal was only slightly affected by the slaughter season, it was markedly
      changed by the muscle type. However, PDO veal had values of pasture-fed cattle
      for lipid grass intake indicators, in both seasons and muscles. From a human
      health standpoint, intramuscular fat in Mirandesa-PDO veal has a high nutritional
      value throughout the year, with favorable ratios of n-6/n-3 and contents of n-3
      PUFA and alpha-tocopherol, as a result of the beneficial effects of grass
      feeding.

PMID- 22133589
TI  - Identification of hare meat by a species-specific marker of mitochondrial origin.
AB  - Meat species identification in food has gained increasing interest in recent
      years due to public health, economic and legal concerns. Following the consumer
      trend towards high quality products, game meat has earned much attention. The aim
      of the present work was to develop a DNA-based technique able to identify hare
      meat. Mitochondrial cytochrome b gene was used to design species-specific primers
      for hare detection. The new primers proved to be highly specific to Lepus
      species, allowing the detection of 0.01% of hare meat in pork meat by polymerase
      chain reaction (PCR). A real-time PCR assay with the new intercalating EvaGreen
      dye was further proposed as a specific and fast tool for hare identification with
      increased sensitivity (1pg) compared to end-point PCR (10pg). It can be concluded
      that the proposed new primers can be used by both species-specific end-point PCR
      or real-time PCR to accurately authenticate hare meat.

PMID- 22133590
TI  - Carnosic acid dietary supplementation at 0.12% rates slows down meat
      discoloration in gluteus medius of fattening lambs.
AB  - Thirty-two Merino lambs fed barley straw and a concentrate alone (CONTROL) or
      enriched with vitamin E (VITE006) or carnosic acid (CARN006; CARN012) were used
      to assess the effect of these antioxidant compounds on meat quality attributes.
      The animals were slaughtered after being fed for at least 5weeks with the
      experimental diets. The longissimus lumborum samples of VITE006, CARN006 and
      CARN012 groups showed higher values (P<0.001) of L* (lightness) through the
      complete storage period under modified atmosphere when compared to the CONTROL
      group. Moreover, the VITE006 and CARN012 samples revealed lower discoloration
      when compared to the CONTROL group, these differences being more apparent in a
      less color stable muscle such as gluteus medius (P<0.05 for hue after 14days of
      refrigerated storage). Meat sensory traits were not significantly affected by
      carnosic acid and microbiological analyses were not conclusive at the doses
      administered.

PMID- 22133591
TI  - Influence of temporary cement contamination on the surface free energy and
      dentine bond strength of self-adhesive cements.
AB  - OBJECTIVES: The surface free energy and dentine bond strength of self-adhesive
      cements were examined after the removal of temporary cements. METHODS: The labial
      dentine surfaces of bovine mandibular incisors were wet ground with #600-grit SiC
      paper. Acrylic resin blocks were luted to the prepared dentine surfaces using HY
      Bond Temporary Cement Hard (HY), IP Temp Cement (IP), Fuji TEMP (FT) or Freegenol
      Temporary Cement (TC), and stored for 1 week. After removal of the temporary
      cements with an ultrasonic tip, the contact angle values of five specimens per
      test group were determined for the three test liquids, and the surface-energy
      parameters of the dentine surfaces were calculated. The dentine bond strengths of
      the self-adhesive cements were measured after removal of the temporary cements in
      a shear mode at a crosshead speed of 1.0mm/min. The data were subjected to one
      way analysis of variance (ANOVA) followed by Tukey's HSD test. RESULTS: For all
      surfaces, the value of the estimated surface tension component gamma(S)(d)
      (dispersion) was relatively constant at 41.7-43.3 mJm(-2). After removal of the
      temporary cements, the value of the gamma(S)(h) (hydrogen-bonding) component
      decreased, particularly with FT and TC. The dentine bond strength of the self
      adhesive cements was significantly higher for those without temporary cement
      contamination (8.2-10.6 MPa) than for those with temporary cement contamination
      (4.3-7.1 MPa). CONCLUSIONS: The gamma(S) values decreased due to the decrease of
      gamma(S)(h) values for the temporary cement-contaminated dentine. Contamination
      with temporary cements led to lower dentine bond strength. CLINICAL SIGNIFICANCE:
      The presence of temporary cement interferes with the bonding performance of self
      adhesive cements to dentine. Care should be taken in the methods of removal of
      temporary cement when using self-adhesive cements.

PMID- 22133593
TI  - MRI findings in acute Hendra virus meningoencephalitis.
AB  - AIM: To describe serial changes in brain magnetic resonance imaging (MRI) in
      acute human infection from two outbreaks of Hendra virus (HeV), relate these
      changes to disease prognosis, and compare HeV encephalitis to reported cases of
      Nipah virus encephalitis. MATERIALS AND METHODS: The MRI images of three human
      cases (two of which were fatal) of acute HeV meningoencephalitis were reviewed.
      RESULTS: Cortical selectivity early in the disease is evident in all three
      patients, while deep white matter involvement appears to be a late and possibly
      premorbid finding. This apparent early grey matter selectivity may be related to
      viral biology or ribavirin pharmacokinetics. Neuronal loss is evident at MRI, and
      the rate of progression of MRI abnormalities can predict the outcome of the
      infection. In both fatal cases, the serial changes in the MRI picture mirrored
      the clinical course. CONCLUSION: This is the first comprehensive report of serial
      MRI findings in acute human cerebral HeV infection from two outbreaks. The
      cortical selectivity appears to be an early finding while deep white matter
      involvement a late, and possibly premorbid, finding. In both fatal cases, the
      serial changes in MRI mirrored the clinical course.

PMID- 22133594
TI  - An NKG2D-mediated human lymphoid stress surveillance response with high
      interindividual variation.
AB  - DNA damage or other physicochemical stresses may increase the expression of major
      histocompatibility complex class I-related stress antigens, which then activate
      lymphocytes. This lymphoid stress surveillance (LSS) not only can limit tumor
      formation but may also promote immunopathology. MICA is a highly polymorphic
      human stress antigen implicated in tumor surveillance, inflammation, and
      transplant rejection. However, LSS has not been conclusively demonstrated in
      humans, and the functional role for MICA polymorphisms remains to be established.
      We show that MICA coding sequence polymorphisms substantially affected RNA and
      protein expression. All donors tested showed LSS responses of gammadelta T and
      natural killer cells, but unexpectedly, each was individually "tuned." Hence,
      some responded optimally to highly expressed alleles, whereas others responded
      better to lower MICA expression, challenging the orthodoxy that higher stress
      antigen levels promote greater responsiveness. These individual variations in LSS
      tuning may help explain patient-specific differences in tumor immune
      surveillance, transplant rejection, and inflammation, as well as provide insight
      into immune evasion and immunosuppression.

PMID- 22133595
TI  - Perceived duration of chromatic and achromatic light.
AB  - Luminance and color information are considered to be processed in parallel
      systems. The integration of information from these two separate systems is
      crucial for the visual system to produce a coherent percept. To investigate how
      luminance and color lights are perceived in time, we measured the perceived
      duration of light stimuli with and without colors in a paradigm involving
      simultaneous perception with presentation of two successive stimulus frames.
      Luminance contrast and color contrast of the stimuli were set with a chromatic
      substitution technique. In Experiment 1, the perceived duration of both chromatic
      stimuli and achromatic stimuli increased as the luminance contrast decreased.
      Experiment 2 tested if the duration of the percept was influenced by color
      contrast which was defined by colorimetric purity of the stimuli, when luminance
      contrast was set as low as practically possible. The result showed that the
      duration of the percept decreased with increasing color contrast of the stimuli.
      Moreover, Experiment 3 demonstrated that the trend of perceived duration was
      consistent with the four primary colors, provided that the effective color
      contrast of stimulus was corrected based on the contrast sensitivity to the
      color. These experiments indicate that, with a high luminance contrast level,
      perceived duration of a stimulus is predominantly defined by luminance contrast,
      whereas in low luminance contrast conditions, the duration depends on the color
      contrast. The perceived duration of color stimuli showed an "inverse color
      contrast effect", similar to the well-known "inverse intensity effect" for
      luminance stimuli. The similarities and the differences between the two systems,
      as well as their priorities in processing temporal information of visual stimuli
      are further discussed.

PMID- 22133597
TI  - The importance of laryngoscopy during cardiac arrest.

PMID- 22133596
TI  - The expression of the hypoxia markers CA9 and CXCR4 is correlated with survival
      in patients with neuroendocrine tumours of the ileum.
AB  - BACKGROUND/AIM: The hypoxia-inducible factor pathway regulates the expression of
      a diverse group of molecules such as CA9 and CXCR4. Our aim was to investigate
      the expression of these markers in a series of patients with an ileal
      neuroendocrine tumour (IET) at various stages of tumorigenesis. METHODS: The
      immunohistochemical expression of CA9 and CXCR4 was examined in 51 patients with
      a resected IET. A 'hypoxic score' was calculated, integrating the expression of
      both CA9 and CXCR4 (hypoxic score 0: absence of expression of both molecules;
      hypoxic score 1: expression of CXCR4 and/or CA9). Results were compared to
      histoprognostic factors (including tumour size, stage and grade, WHO and TNM
      classifications, presence of vascular or perineural invasion, presence of a
      fibrotic stroma and microvascular density) and to survival. RESULTS: All tumours
      were well differentiated. 69% of tumours were less than 25 mm. 46% of tumours
      largely infiltrated the intestinal wall (>=T3, subserosa and serosa) and 90% were
      classified as N1 and/or 63% as M1. 57% of tumours were of grade G1, 43% of grade
      G2. Grade G2 (p=0.004) and larger tumour infiltration (>=T4; p=0.03) correlated
      with lower survival. Hypoxic score 1 correlated with a greater tumour size
      (p=0.034), larger tumour infiltration (T3 or T4; p=0.001), grade G2 (p=0.046),
      presence of lymph node metastasis (p=0.0066) and with lower survival of patients
      (p=0.03). CONCLUSION: The hypoxia-inducible factors CA9 and CXCR4 were found
      associated to the malignant progression of neuroendocrine tumours of the ileum.
      Their expression may reflect higher tumour aggressivity.

PMID- 22133598
TI  - Decomposing gender differences in low-density lipoprotein cholesterol among
      veterans with or at risk for cardiovascular illness.
AB  - OBJECTIVES: To measure the extent to which gender differences in poor lipid
      control among individuals at risk for cardiovascular diseases could be explained
      by patient-level characteristics. STUDY DESIGN: Cross-sectional analyses of
      merged Veteran Health Administration (VHA) and Medicare claims data for the
      fiscal years (FY) 2002 and 2003 consisting of veterans using VHA facilities and
      were diagnosed with diabetes or heart disease or hypertension during FY 2002 and
      had recorded LDL cholesterol values in FY2003 (N = 527,568). There were 10,582
      women and 516,986 men veterans. Poor lipid control was defined as LDL cholesterol
      values >=130 mg/dL. Multivariate techniques consisted of logistic regressions.
      Based on the parameter estimates and distribution of individual characteristics,
      we used a decomposition technique to analyze factors that contributed to the
      gender difference in poor lipid control. PRINCIPAL FINDINGS: A significantly
      higher percent of women (27.4%) than men (17.1%) had LDL cholesterol values >=130
      mg/dL. Of the 10.3 percentage point difference in lipid control, 3.4 percentage
      points were explained by variables included in the model. The gender difference
      in poor lipid control was mostly explained by age, physical illnesses, use of
      lipid lowering medications and depression. CONCLUSIONS: Only one-third of the
      gender difference in poor lipid control could be explained by differences in
      individual characteristics, some of which are modifiable or could be used to
      identify groups at risk with poor lipid control. Our findings suggest that gender
      differences in lipid control could be partially reduced by increasing the
      prescription of lipid lowering drugs and treating depression among women.
      Interventions that improve lipid control in the non-elderly will also benefit
      women. However the largest part of the difference in lipid control between women
      and men remains unexplained and further research is needed to identify additional
      modifiable and unmodifiable factors.

PMID- 22133599
TI  - Electrical transport properties of CuS single crystals.
AB  - Electrical resistivity, transverse magnetoresistance and thermoelectric power
      measurements were performed on CuS high quality single crystals in the range 1.2
      300 K and under fields of up to 16 T. The zero field resistivity data are well
      described below 55 K by a quasi-2D model, consistent with a carrier confinement
      at lower temperatures, before the transition to the superconducting state. The
      transverse magnetoresistance develops mainly below 30 K and attains values as
      large as 470% for a 16 T field at 5 K, this behaviour being ascribed to a band
      effect mechanism, with a possible magnetic field induced DOS change at the Fermi
      level. The transverse magnetoresistance shows no signs of saturation, following a
      power law with field Deltarho/rho(0) ? H(1.4), suggesting the existence of open
      orbits for carriers at the Fermi surface. The thermoelectric power shows an
      unusual temperature dependence, probably as a result of the complex band
      structure of CuS.

PMID- 22133600
TI  - S. Hickson-Curran, et al. "Patient attitudes and behavior regarding hygiene and
      replacement of soft contact lenses and storage cases" [Contact Lens Anterior Eye
      (2011), doi:10.1016/j.clae.2010.12.005].

PMID- 22133601
TI  - Compression-induced muscle injury in rats that mimics compartment syndrome in
      humans.
AB  - Compartment syndrome (CS) is a serious complication arising from a variety of
      extremity injuries and resultant swelling within the fascicles of the muscle
      tissue. The current standard of care for CS is fasciotomy, which relieves the
      intracompartmental pressure of CS but inflicts further tissue damage. The
      development of new techniques to treat CS include angiogenic therapy,
      antifibrosis treatments, and stem cell therapy, all which aim to enhance tissue
      regeneration and functional recovery. Current rodent models of skeletal muscle
      injury do not accurately mimic the complex physiological tissue damage found in
      CS in human patients, and large-animal models of CS cannot be used as an
      experimental model of human cell therapy because of the lack of immunocompromised
      animals. We developed a rat model of CS that mimics the sequelae of the human
      condition. Compression of the hindlimb of rats using neonatal blood pressure
      cuffs maintaining 120 to 140 mmHg for 3 hours resulted in considerable muscular,
      vascular, and neural damage. Histological and functional analyses documented the
      initial degeneration and subsequent regeneration of the muscle tissue over time.
      The complex muscular, vascular, and neural injury observed in this model provides
      an ideal platform for testing cellular, biological, and pharmacological agents
      for the restoration of muscle volume and function.

PMID- 22133602
TI  - Bio-isoprene production using exogenous MVA pathway and isoprene synthase in
      Escherichia coli.
AB  - In this paper, an original strategy is employed to biosynthesize the isoprene by
      heterologously co-expressing the Saccharomyces cerevisiae MVA pathway and
      isoprene synthase (IspS) from Populus alba in the Escherichia coli BL21 (DE3)
      strain, which was screened from three different IspS enzymes. The finally genetic
      strain YJM13 harboring the MVA pathway and ispS(Pa) gene could accumulate
      isoprene up to 2.48 mg/l and 532 mg/l under the flask and fed-batch fermentation
      conditions, respectively, which is about three times and five times to the
      control strain. The result proves to be higher than that in the report documents.
      In this way, a potential production system for isoprene from renewable sources
      via the MVA pathway in E. coli has been provided.

PMID- 22133603
TI  - A new beta-glucosidase producing yeast for lower-cost cellulosic ethanol
      production from xylose-extracted corncob residues by simultaneous
      saccharification and fermentation.
AB  - This study reports a new yeast strain of Clavispora NRRL Y-50464 that is able to
      utilize cellobiose as sole source of carbon and produce sufficient native beta
      glucosidase enzyme activity for cellulosic ethanol production using SSF. In
      addition, this yeast is tolerant to the major inhibitors derived from
      lignocellulosic biomass pre-treatment such as 2-furaldehyde (furfural) and 5
      (hydroxymethyl)-2-furaldehyde (HMF), and converted furfural into furan methanol
      in less than 12h and HMF into furan-2,5-dimethanol within 24h in the presence of
      15 mM each of furfural and HMF. Using xylose-extracted corncob residue as
      cellulosic feedstock, an ethanol production of 23 g/l was obtained using 25%
      solids loading at 37  degrees C by SSF without addition of exogenous beta
      glucosidase. Development of this yeast aids renewable biofuels development
      efforts for economic consolidated SSF bio-processing.

PMID- 22133604
TI  - New plant-growth medium for increased power output of the Plant-Microbial Fuel
      Cell.
AB  - In a Plant-Microbial Fuel Cell anode-conditions must be created that are
      favorable for plant growth and electricity production. One of the major aspects
      in this is the composition of the plant-growth medium. Hoagland medium has been
      used until now, with added phosphate buffer to reduce potential losses over the
      membrane because of differences in pH between anode and cathode. We developed a
      new, improved plant-growth medium that improves current production, while the
      plant keeps growing. This medium is a nitrate-less, ammonium-rich medium that
      contains all macro- and micro-nutrients necessary for plant growth, with a
      balanced amount of bicarbonate buffer. Sulphate presence in the plant-growth
      medium helps to keep a low anode-potential. With the new plant-growth medium the
      maximum current production of the Plant-Microbial Fuel Cell increased from 186
      mA/m(2) to 469 mA/m(2).

PMID- 22133605
TI  - Rheological properties of algae slurries for minimizing harvesting energy
      requirements in biofuel production.
AB  - Rheological properties of microalgae slurries were measured as a function of
      biomass concentration from 0.5 to 80 kg/m(3) for Nannochloris sp., Chlorella
      vulgaris, and Phaeodactylum tricornutum. At biomass concentrations smaller than
      20 kg/m(3), all slurries displayed a Newtonian fluid behavior with less than 30%
      increase in the effective viscosity from that of the nutrient medium. However, at
      biomass concentrations larger than 60 kg/m(3), the slurries of the green algae,
      Nannochloris sp. and C. vulgaris, displayed a shear thinning non-Newtonian
      behavior with varying degrees of sensitivity to shear rate while that of the
      diatom, P. tricornutum, was still a Newtonian fluid up to 80 kg/m(3). Moreover,
      bioenergy pumping effectiveness showed significant deviation among different
      species in the non-Newtonian regime. Finally, dewatering the slurries to
      concentration factors larger than 80 did not further increase the total bioenergy
      harvest effectiveness.

PMID- 22133606
TI  - Long term performance of an AMD treatment bioreactor using chemolithoautotrophic
      sulfate reduction and ferrous iron precipitation under in situ groundwater
      conditions.
AB  - Chemolithoautotrophic sulfate reduction (CSR) was tested to treat natural acid
      mine drainage influenced groundwaters. The long term behavior was studied for
      more than 3 years under groundwater conditions (10  degrees C, autochthonous
      sulfate reducing bacteria (SRB)) without biomass replenishment in a 190 L bench
      scale reactor. The process produces water with alkalinity >10 mM. pH can be
      controlled by p(CO(2)) for all expectable water qualities. SRB were immobilized
      using an expanded clay bed. After 1.3 years of operation, a constant biomass
      content and sulfate reduction rate of 0.25-0.30 mmol(so)4(Lh)-1 were established.
      The sulfate reduction rate was limited by biomass content. Most of the electrons
      were used for sulfate reduction (98%). The hydrogen turn over in competing
      processes like methanogenesis and homoacetogenesis was successfully suppressed by
      adjusting the sulfate concentration to be >2 mM in the runoff.

PMID- 22133607
TI  - Hydrogen and volatile fatty acid production during fermentation of cellulosic
      substrates by a thermophilic consortium at 50 and 60  degrees C.
AB  - The purpose of this study was to characterize the effect of temperature and
      cellulosic substrates on fermentative metabolites, H(2) production, and community
      successions in an anaerobic, cellulolytic consortium, TC60. Pyrosequencing
      analysis indicated that the consortium was predominated by Thermoanaerobacter and
      Clostridium spp. Metabolite production was analyzed with four cellulosic
      substrates at 4 kg/m(3). Triplicate cultures of each substrate were incubated at
      50 or 60  degrees C. The main fermentation products (H(2), CO(2), ethanol, and
      acetate) were monitored over time. The ANOVA model for production rates showed a
      significant temperature effect (P<0.05) on all products. Increased temperature
      promoted higher H(2), CO(2), and ethanol yields while acetate yields were only
      affected prior to 24h of incubation. In addition to individual effects discerned
      in the model, ANOVA indicated significant interactions between the substrate and
      temperature. These interactions have not been previously recognized in the
      literature for cellulolytic and hydrogen-producing microorganisms.

PMID- 22133608
TI  - Fatal intracerebral hemorrhage associated with administration of recombinant
      tissue plasminogen activator in a stroke patient on treatment with dabigatran.

PMID- 22133609
TI  - The manganese ion of the heterodinuclear Mn/Fe cofactor in Chlamydia trachomatis
      ribonucleotide reductase R2c is located at metal position 1.
AB  - The essential catalytic radical of Class-I ribonucleotide reductase is generated
      and delivered by protein R2, carrying a dinuclear metal cofactor. A new R2
      subclass, R2c, prototyped by the Chlamydia trachomatis protein was recently
      discovered. This protein carries an oxygen-activating heterodinuclear
      Mn(II)/Fe(II) metal cofactor and generates a radical-equivalent Mn(IV)/Fe(III)
      oxidation state of the metal site, as opposed to the tyrosyl radical generated by
      other R2 subclasses. The metal arrangement of the heterodinuclear cofactor
      remains unknown. Is the metal positioning specific, and if so, where is which ion
      located? Here we use X-ray crystallography with anomalous scattering to show that
      the metal arrangement of this cofactor is specific with the manganese ion
      occupying metal position 1. This is the position proximal to the tyrosyl radical
      site in other R2 proteins and consistent with the assumption that the high-valent
      Mn(IV) species functions as a direct substitute for the tyrosyl radical.

PMID- 22133610
TI  - Split-intein mediated re-assembly of genetically encoded Ca(2+) indicators.
AB  - While genetically encoded Ca(2+) indicators (GECIs) allow Ca(2+) imaging in model
      organisms, the gene expression is often under the control of a single promoter
      that may drive expression beyond, the cell types of interest. To enable more cell
      type specific targeting, GECIs can be brought under the, control of the
      intersecting expression from two promoters. Here, we present the splitting and,
      reassembly of two representative GECIs (TN-XL and GCaMP2) mediated by the split
      intein from Nostoc, punctiforme (NpuDnaE). While the split TN-XL biosensor
      offered ratiometric Ca(2+) imaging, it had a, diminished Ca(2+) response relative
      to the native TN-XL biosensor. In contrast, the split GCaMP2, biosensor retained
      similar Ca(2+) response to the native GCaMP2. The split GCaMP2 biosensor was,
      further targeted to the pharyngeal muscles of Caenorhabditis elegans where Ca(2+)
      signals from feeding C. elegans, were imaged. Thus, we envision that increased
      cell-type targetability of GECIs is feasible with two, complementary promoters.

PMID- 22133611
TI  - Dynamics of mitochondrial [Ca(2+)] measured with the low-Ca(2+)-affinity dye rhod
      5N.
AB  - Available methods to measure mitochondrial [Ca(2+)] ([Ca(2+)](M)) include both
      targeted proteins and fluorescent dyes. Targeted proteins usually report much
      higher [Ca(2+)](M) values than fluorescent dyes, up to two orders of magnitude.
      However, we show here that the low-Ca(2+)-affinity dye rhod-5N provides
      [Ca(2+)](M) values similar to those reported by targeted aequorin, suggesting
      that the discrepancies are mainly due to the higher Ca(2+)-affinity of the
      fluorescent dyes used. We find rhod-5N has an apparent in situ intramitochondrial
      Kd around 0.5mM. Addition of Ca(2+) buffers containing between 4.5 and 10MUM
      [Ca(2+)] to permeabilized cells loaded with rhod-5N induced increases in
      calibrated [Ca(2+)](M) up to the 100MUM-1mM range, which were dependent on
      mitochondrial membrane potential. Ca(2+) release from mitochondria was largely
      dependent on [Na(+)]. We have then used rhod-5N loaded cells to investigate the
      [Ca(2+)](M) response to agonist stimulation at the single-cell and subcellular
      level. The [Ca(2+)](M) peaks induced by histamine varied by nearly 10-fold among
      different cells, with a mean about 25MUM. In the presence of the Ca(2+) uniporter
      stimulator kaempferol, the [Ca(2+)](M) peaks induced by histamine were also
      highly variable, and the mean [Ca(2+)](M) peak was 3-fold higher. Simultaneous
      measurement of cytosolic and mitochondrial [Ca(2+)] peaks showed little
      correlation among the heights of the peaks in both compartments. Studying the
      [Ca(2+)](M) peaks at the subcellular level, we found significant heterogeneities
      among regions in the same cell. In particular, the [Ca(2+)](M) increase in
      mitochondrial regions close to the nucleus was more than double that of
      mitochondrial regions far from the nucleus.

PMID- 22133612
TI  - Hormone impact: BPA linked to altered gene expression in humans.

PMID- 22133614
TI  - Mitf is a transcriptional activator of medaka germ genes in culture.
AB  - Germ cells express a unique subset of genes called germ genes mostly encoding RNA
      binding proteins such as Dazl, Dnd and Vasa. How germ gene expression is
      controlled remains illusive, because in no organism has a transcription factor
      been identified that regulate expression of these genes. Microphthalmia
      associated transcription factor (Mitf) has been reported to show expression in
      male mouse germ cells of the adult testis. Here we report in the fish medaka
      (Oryzias latipes) that Mitf is a transcription activator of germ gene expression.
      Mitf is a master regulator of melanocyte development, which activates melanogenic
      genes through binding to the E-box containing consensus CANNTG. The E-box was
      found to be present in 23-26 copies in the promoters of medaka germ genes dazl,
      dnd and vasa. Importantly, forced Mitf expression enhanced the transcriptional
      activity of the three gene promoters by up to more than 10 fold and remarkably
      increased the level of endogenous dazl, dnd and vasa transcripts in cell culture.
      Transfection of Mitf expression vectors was sufficient to induce directed
      differentiation of medaka embryonic stem cells into melanocytes. Fluorescence in
      situ hybridization revealed the expression of both medaka mitf genes in adult
      germ cells of male and female gonads. Mitf is well-known as the melanocyte master
      regulator. Our results offer first evidence that Mitf may act as a
      transcriptional activator of germ gene expression in medaka.

PMID- 22133615
TI  - Antioxidant effects of resveratrol and other stilbene derivatives on oxidative
      stress and *NO bioavailability: Potential benefits to cardiovascular diseases.
AB  - Oxidative stress plays an important part in the appearance and development of
      cardiovascular diseases. In this context, overproduction of reactive oxygen
      species leads to deregulation of metabolic pathways, such as cell proliferation
      or inflammation, which interferes with the homeostasis of vascular endothelium.
      Oxidative stress can decrease the bioavailability of nitric oxide (*NO) in
      vessels. This decrease is highly associated with endothelial dysfunction. The
      "French paradox" is a phenomenon that associates a diet rich in saturated fatty
      acids and a moderate consumption of wine to a low prevalence of cardiovascular
      diseases. During the past 10 years, the beneficial effects of wine on
      cardiovascular diseases have been attributed to the actions of resveratrol and
      other polyphenols. One of the mechanisms involved in these beneficial effects is
      the capacity of resveratrol and some other stilbene derivatives to maintain
      sufficient *NO bioavailability in vascular endothelium. This review presents the
      latest findings on the molecular effects of resveratrol and other stilbene
      derivatives on the various actors that modulate *NO bioavailability during
      oxidative stress.

PMID- 22133616
TI  - Vav1 in differentiation of tumoral promyelocytes.
AB  - The multidomain protein Vav1, in addition to promote the acquisition of
      maturation related properties by normal hematopoietic cells, is a key player in
      the ATRA- and PMA-induced completion of the differentiation program of tumoral
      myeloid precursors derived from APL. This review is focussed on the role of Vav1
      in differentiating promyelocytes, as part of interconnected networks of
      functionally related proteins ended to regulate different aspects of myeloid
      maturation. The role of Vav1 in determining actin cytoskeleton reorganization
      alternative to the best known function as a GEF for small G proteins is
      discussed, as well as the binding of Vav1 with cytoplasmic and nuclear signaling
      molecules which provides a new perspective in the modulation of nuclear
      architecture and activity. In particular, new hints are provided on the ability
      of Vav1 to determine the nuclear amount of proteins implicated in modulating mRNA
      production and stability and in regulating the ATRA-dependent protein expression
      also by direct interaction with transcription factors known to drive the ATRA
      induced maturation of myeloid cells. The reviewed findings summarize the major
      advances in the understanding of additional, non conventional functions connected
      with the vast interactive potential of Vav1.

PMID- 22133617
TI  - Evaporation front compared with crust thickness in potato deep-fat frying.
AB  - The various theoretical approaches that have been proposed for modeling heat and
      mass transport during deep-fat frying of potatoes provide a rather ambiguous view
      of the relation between the propagation of the evaporation front inside the food
      and the evolution of crust thickness. This can be partly attributed to the
      unavailability of detailed experimental information concerning the temperature
      field inside the developing crust to validate the models. The objective of the
      present work is to experimentally study the relation between crust thickness
      evolution and evaporation front propagation and how this varies with frying
      conditions. To achieve this goal, a special device has been constructed that
      permits (1) only 1 side of a potato stick to be exposed to hot oil, and (2)
      accurate and stable placement of miniature thermocouples in prescribed positions
      under but very close to the potato surface. Temperature recordings inside the
      developing crust allowed identification of different heating regimes during
      frying and a rough estimation of the evaporation front propagation. In addition,
      crust thickness was determined at intermittent time intervals by 2 independent
      methods (1) microphotography and (2) a micrometer. Comparison of the evaporation
      front propagation with crust thickness evolution indicates an interrelationship
      roughly up to the end of the boiling regime (bubble-end point). After this
      moment, the propagation of the evaporation front is faster than the evolution of
      crust thickness. PRACTICAL APPLICATION: Understanding the role of parameters that
      determine crust formation is of paramount importance since crust characteristics
      such as thickness and texture dictate the sensory perception of fried foods. This
      study aims to quantify the relationship between such parameters (that is, crust
      evolution and the propagation of the evaporation front inside the food) and to
      examine how frying conditions (oil temperature and frying duration) affect it. In
      addition, the present findings may be of particular value to deterministic
      modeling efforts on the coupled heat and mass transfer phenomena during deep-fat
      frying.

PMID- 22133618
TI  - Sleep disturbances and interleukin 6 receptor inhibition in rheumatoid arthritis.
AB  - OBJECTIVE: Interleukin 6 (IL-6)-mediated interactions have been associated with
      sleep disturbances in healthy subjects. In this pilot study we examined whether
      administration of the IL-6 receptor antagonist tocilizumab in patients with
      rheumatoid arthritis (RA) affects sleep disturbances. METHODS: Fifteen patients
      (13 women) with sleep disturbances at baseline received 6 monthly infusions of
      tocilizumab 8 mg/kg for moderately or severely active RA. Sleep quality was
      assessed by Pittsburgh Sleep Quality Index (PSQI), daytime sleepiness by Epworth
      Sleepiness Scale, disease activity by the 28-joint Disease Activity Score
      erythrocyte sedimentation rate, functional disability by Health Assessment
      Questionnaire Disability Index (HAQ-DI), and fatigue by the Functional Assessment
      of Chronic Illness Therapy (FACIT-Fatigue Scale; FFS) at baseline and first,
      second, third, and sixth month of treatment. Medications used before enrollment
      remained unchanged during followup. RESULTS: Sleep quality improved and daytime
      sleepiness decreased significantly at first-month assessment (p < 0.00001 and p <
      0.004, respectively, by repeated measurement analysis) compared to baseline, and
      these changes became more evident through 6 months. Disease activity decreased,
      fatigue decreased, and functional status improved significantly. Changes in PSQI
      score over time were not associated with the corresponding changes in DAS28-ESR
      (r = 0.37, p = 0.17), but correlated significantly with HAQ-DI changes (r = 0.60,
      p = 0.02) and marginally with changes in FFS scores (r = -0.46, p = 0.08).
      CONCLUSION: Improvement of sleep quality after tocilizumab treatment in patients
      with RA does not appear to directly result from decreased disease activity,
      further suggesting that aberrant IL-6 regulation is associated with sleep
      disturbances.

PMID- 22133619
TI  - Prevalence of vertebral compression fractures and associated factors in children
      and adolescents with severe juvenile idiopathic arthritis.
AB  - OBJECTIVE: Vertebral fractures occur in patients with juvenile idiopathic
      arthritis (JIA), but data on their frequency and causes are scarce. Our cross
      sectional study evaluated prevalence of compression fractures and associated
      factors in a high-risk pediatric population with severe JIA. METHODS: Children
      and adolescents with a history of treatment-resistant polyarticular-course JIA
      for >= 5 years or systemic arthritis for >= 3 years were recruited. Clinical
      examination, dietary recall, laboratory measurements, bone mineral density (BMD)
      measurement by dual-energy X-ray absorptiometry, and spinal radiography were
      performed. RESULTS: Our study included 50 patients (41 girls), of whom 6 (12%)
      had systemic arthritis, with a median age of 14.8 years (range 7.0-18.7 yrs) and
      median disease duration of 10.2 years (range 3.9-16.8 years). Ninety-four percent
      had used systemic glucocorticoids (GC); the median total duration of GC treatment
      was 7.1 years (range 0-15.5 yrs). The median weight-adjusted cumulative GC dose
      for the preceding 3 years was 72 mg/kg (range 0-911 mg/kg). The median bone age
      corrected lumbar spine and whole-body areal BMD Z-scores were -0.8 and -1.0,
      respectively. Twenty-two percent had vertebral fractures, mostly thoracic.
      Compression fractures were associated with high disease activity, high body mass
      index (BMI), and high recent cumulative GC dose, but not with disease duration or
      BMD. Thirty percent had sustained at least 1 peripheral low energy fracture.
      Twenty-six percent were deemed to have significantly compromised bone health.
      CONCLUSION: Severe JIA is associated with a significant risk of vertebral
      compression fractures. Associated factors include high disease activity, high
      BMI, and high recent GC exposure. Further studies are needed to establish optimal
      prevention and treatment guidelines.

PMID- 22133620
TI  - Clinical course and management of a consecutive series of patients with "healed
      temporal arteritis".
AB  - OBJECTIVE: To describe the clinical course and management of patients with a
      pathologic diagnosis of "healed" giant cell arteritis (GCA), and to determine
      whether previously published histological descriptions of healed arteritis can
      identify patients with a greater likelihood of clinically significant arteritis.
      METHODS: All temporal artery biopsy reports between 1994 and 2003 were examined
      for a diagnosis of "healed arteritis." Two rheumatologists abstracted the medical
      record for presenting features, physical findings, comorbid conditions, and data
      on treatment and outcomes. One pathologist, blinded to the clinical data,
      reviewed all specimens and reinterpreted the biopsies according to published
      histological descriptions of healed arteritis. RESULTS: Forty-seven patients with
      an initial pathologic diagnosis of healed arteritis were identified. In 54% of
      these patients, corticosteroid therapy did not change after the diagnosis of
      healed arteritis was documented in the pathology report. Seventy percent were
      ultimately treated with no corticosteroids or low-moderate corticosteroid
      regimens. Only 32% of the initial cases were confirmed upon review of the
      biopsies using standardized histological criteria. Patients with confirmed healed
      arteritis were more likely to have a documented history of polymyalgia
      rheumatica/GCA and a longer duration of corticosteroid treatment before biopsy.
      These patients were not more likely to have adverse outcomes. CONCLUSION: In this
      case series, the diagnosis of healed arteritis had little effect on treatment
      decisions. In most cases, the initial pathologic diagnosis of healed arteritis
      was not confirmed when biopsies were reviewed by a single pathologist using
      uniform histological criteria.

PMID- 22133622
TI  - A dose schedule for intraarticular steroids in juvenile arthritis.
AB  - OBJECTIVE: To determine whether the intraarticular (IA) dose of triamcinolone
      hexacetonide (TH) or triamcinolone acetonide (TA) influences time to relapse
      among patients with juvenile idiopathic arthritis (JIA). METHODS: The primary
      endpoint variable was the time to relapse of arthritis in the affected joint
      after an intraarticular (IA) injection. A relapse was defined as the reoccurrence
      of active arthritis in the injected joint. Analysis was carried out including
      only the first IA joint injection for each patient. Further analysis was
      conducted including the first knee injection alone. A separate analysis within
      the IA corticosteroid groups was performed using the Spearman rank coefficient,
      to determine if dose of IA steroid affected time to relapse. RESULTS: Records
      from 186 patients with JIA (145 females, 41 males) injected with either TH or TA
      were collected from January 1995 through December 2003. All subjects were
      followed for a minimum of 15 months from the time of IA injection. Of the 794
      joint injections, 422 (53.1%) were injected with TH and 372 (46.9%) with TA.
      There were 111 first joint injections (all joints) with TH and 70 with TA. There
      were 89 first joint injections (knee only) with TH and 56 with TA. TH proved more
      effective than TA with respect to the time to relapse for first injection into
      all joints (10.47 +/- 0.42 mo vs 8.66 +/- 0.59 mo; p < 0.001), and for first
      injections into knee only (11.04 +/- 0.44 vs 8.99 +/- 0.65 mo; p < 0.001). IA
      doses ranged from 0.4 to 4 mg/kg (mean 1.56 +/- 0.76) for TH and from 0.5 to 8
      mg/kg (mean 2.54 +/- 1.74) for TA. There was no correlation between time to
      relapse and dose of either TH and TA (r = 0.1, p > 0.5). There was no correlation
      between time to relapse and sex, duration of illness, age of patient, concurrent
      medications, or subtype of JIA. CONCLUSION: In a larger dataset (794 injections)
      we have confirmed our previous findings (227 injections) that TH is a more
      effective IA corticosteroid than TA. In this much larger data analysis, dose of
      IA corticosteroid in the range we studied did not significantly influence the
      duration of response.

PMID- 22133621
TI  - Racial differences in knee osteoarthritis pain: potential contribution of
      occupational and household tasks.
AB  - OBJECTIVE: We examined whether occupational and household tasks contributed to
      differences in pain between African Americans and whites with radiographic knee
      osteoarthritis (OA). METHODS: Participants from the Johnston County
      Osteoarthritis Project self-reported the frequency (often/always vs
      never/seldom/sometimes) of performing 9 occupational tasks involving lower
      extremity joint loading at their longest job (N = 868) and current job (N = 273),
      as well as 8 household tasks ever performed (N = 811) and currently being
      performed (N = 767). The associations of the numbers of occupational or household
      tasks with the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) pain subscale were first examined in simple linear regression models. If
      significantly associated with greater pain, each of these was included in
      adjusted linear regression models to examine whether the association of race with
      pain remained statistically significant. RESULTS: African Americans reported
      significantly greater WOMAC pain scores than whites. Exposures to more
      occupational tasks at the longest job and the current job were associated with
      greater WOMAC pain scores (p < 0.01). The association of race with greater pain
      scores remained statistically significant when controlling for occupational tasks
      at the longest job, but was reduced by 26% and no longer significant when
      controlling for the number of current occupational tasks. Exposures to an
      increasing number of household tasks were associated with lower pain scores and
      were not further analyzed. CONCLUSION: Current performance of physically
      demanding occupational tasks contributed to racial differences in pain severity
      among individuals with knee OA. Better workplace policies to accommodate OA
      related limitations may help to reduce racial differences in pain.

PMID- 22133623
TI  - Concomitant septic arthritis in crystal monoarthritis.
AB  - OBJECTIVE: In acute monoarthritis, the presence of crystals in synovial fluid may
      lead to a diagnosis of crystal arthritis (CA) before septic arthritis (SA) can be
      excluded by culture. We aimed to identify the frequency of coexistence of CA with
      SA and to compare these with regard to synovial fluid microscopy, C-reactive
      protein (CRP), and blood culture. METHODS: We examined 1612 synovial aspirates
      from 2004 to 2009 retrospectively. Of these, 104 patients with clinically
      significant SA were identified. These were compared to 295 patients with isolated
      CA. RESULTS: Five percent of joints with CA had concomitant infection. A high
      synovial white blood cell (WBC) count and elevated CRP (> 100 mg/l) were
      predictive of concomitant SA with a sensitivity of 86.4%, specificity of 48.3%
      and 54.6%, and negative predictive values of 98.5% and 98.7%, respectively. In
      patients with SA who had a blood culture, 42.5% were positive with a matching
      organism. SA of the shoulder had a 90% rate of bacteremia. CONCLUSION: Crystals
      alone in synovial fluid from acute monoarthritis cannot exclude SA, as CA and SA
      frequently coexist. High WBC counts and elevated CRP are common to both SA and
      CA. Blood cultures should be collected and septic arthritis considered, even when
      crystals are present, particularly if the shoulder is affected. The exception is
      when Gram stain is negative and the CRP is < 100 mg/l and joint WBC count is <
      10,000/MUl. In these circumstances it is very unlikely that there will be
      concomitant SA.

PMID- 22133624
TI  - Clinically relevant outcomes based on analysis of pooled data from 2 trials of
      duloxetine in patients with knee osteoarthritis.
AB  - OBJECTIVE: To determine response with duloxetine versus placebo in patients with
      osteoarthritis (OA) of the knee using the Outcome Measures in Rheumatoid
      Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT
      OARSI) responder index and other clinically relevant outcomes including minimal
      clinically important improvement (MCII) and patient acceptable symptom state
      (PASS) for pain and function. METHODS: Data were pooled from two 13-week,
      randomized, double-blind, placebo-controlled trials comparing duloxetine 60 to
      120 mg/day with placebo in patients with symptomatic OA of the knee. Treatment
      response was determined according to the OMERACT-OARSI responder index, >= 30%
      pain reduction, >= 50% pain reduction, and MCII and PASS for pain and function.
      (ClinicalTrials.gov identifiers NCT00433290 and NCT00408421) RESULTS: Duloxetine
      treated patients were 33% more likely to experience an OMERACT-OARSI response
      than placebo-treated patients [p < 0.001, number needed to treat (NNT) = 6]. A
      significantly greater percentage of duloxetine-treated patients, compared with
      placebo-treated patients, reported >= 30% improvement in pain from baseline to
      endpoint (p < 0.001, NNT = 5) and >= 50% improvement in pain relative to baseline
      (p < 0.001, NNT = 7). The duloxetine-treated patients were also more likely to
      fulfill MCII criteria for pain (p < 0.001, NNT = 6) and function (p < 0.001, NNT
      = 7), and to achieve PASS for pain (p < 0.001, NNT = 6) and function (p = 0.009,
      NNT = 9). More duloxetine-treated patients compared with placebo-treated patients
      experienced >= 1 treatment-emergent adverse event (p = 0.003, number needed to
      harm = 8). CONCLUSION: Significantly more patients receiving duloxetine than
      placebo achieved an OMERACT-OARSI response, improvements in pain and function
      exceeding the level accepted as MCII, and reached PASS. Results support the
      clinical relevance of outcomes of prior duloxetine studies in symptomatic OA of
      the knee.

PMID- 22133625
TI  - Tumor necrosis factor blockade differentially affects innate inflammatory and
      Th17 cytokines in rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the effect of a tumor necrosis factor-alpha (TNF-alpha)
      inhibitor (etanercept) on innate inflammatory and Th17 cytokines in patients with
      rheumatoid arthritis (RA). METHODS: Serum samples were collected from 40 patients
      with active RA refractory to conventional disease-modifying antirheumatic drugs
      who initiated therapy with etanercept plus methotrexate (MTX). Treatment response
      was assessed at Week 24 according to the European League Against Rheumatism
      response criteria. Serum levels of interleukin 6 (IL-6), TNF-alpha, IL-32, IL-23,
      IL-17A, IL-21, and IL-22 were measured in patients with RA and 25 healthy
      controls. RESULTS: Patients with RA had increased levels of IL-6 (p < 0.001), IL
      32 (p < 0.001), IL-23 (p < 0.001), and a trend toward increased IL-21 in the sera
      compared to controls. At 24 weeks' posttreatment, followup serum samples of
      etanercept responders had decreased levels of IL-6 (p < 0.001) and increased IL
      21 (p < 0.05) and IL-32 (p < 0.001), while there were no differences in cytokine
      levels in non-responders. Serum IL-6 levels were positively correlated with
      levels of erythrocyte sedimentation rate (r = 0.458, p < 0.01), C-reactive
      protein (r = 0.593, p < 0.01), and 28-joint Disease Activity Score (r = 0.432, p
      < 0.01) at baseline. Serum IL-21 levels were positively correlated with levels of
      rheumatoid factor (r = 0.513, r = 0.633, both p < 0.01) and antimutated
      citrullinated vimentin antibodies (r = 0.515, p < 0.01; r = 0.428, p < 0.05) at
      baseline and after 24 weeks of treatment with etanercept. CONCLUSION: Multiple
      inflammatory pathways contribute to persistent chronic inflammation in RA. In
      contrast to nonresponders, etanercept therapy modulated serum cytokine levels and
      caused a marked decrease of IL-6 levels in responders. IL-21 might be involved in
      the regulation of autoantibody production in RA.

PMID- 22133626
TI  - Improvement of prostate treatment by anterior proton fields.
AB  - PURPOSE: We performed a treatment planning study to demonstrate the potential
      dosimetric benefits of anterior-oriented fields for prostate irradiation by
      proton beam. A novel in vivo beam range control method shows millimeter accuracy,
      suggesting that such fields could be safely used to spare the rectum given the
      sharp distal penumbra of protons. METHODS AND MATERIALS: Ten prostate patients
      treated with water-filled endorectal balloon were selected. Bilateral fields were
      planned following the conventional treatment protocol. Three anterior-oriented
      fields (0, +30, -30 degrees ) were planned, with the range compensators manually
      adjusted to improve rectal sparing. Dose distributions to the clinical target
      volume, rectum, anterior rectal wall (ARW), bladder, bladder wall (BW), and
      femoral heads were compared for: A) equally weighted bilateral fields, B) a
      single straight anterior field, and C) two equally weighted anterior-oblique
      fields. RESULTS: The anterior-oriented fields required much less beam energy, ~10
      cm water equivalent path length less than lateral fields. For ARW, the V(95%) for
      Plans A, B, and C were 39%, 8%, and 6%, respectively; the corresponding V(80%)
      were 59%, 27%, and 26%, respectively (p = 0.002 when Plan A was compared with B
      or C). Plan B irradiated a larger volume of BW than did Plan A by 3% at V(95%),
      11% at V(80%), and 16% at V(50%) (p = 0.002), whereas Plan C differs little from
      Plan A for BW at these dose levels. The femoral heads received ~40% of the
      prescription dose in Plan A, but negligible dose in Plans B and C. CONCLUSIONS:
      Compared to lateral fields, anterior-oriented fields can significantly reduce
      dose to the ARW, particularly at high dose levels. These fields alone, or in
      combination with lateral fields, allow for the possibility of either reducing
      treatment toxicity at current prescription doses or further dose escalation in
      the treatment of prostate cancer.

PMID- 22133627
TI  - Training social cognition: from imitation to Theory of Mind.
AB  - Evidence for successful socio-cognitive training in typical adults is rare. This
      study attempted to improve Theory of Mind (ToM) and visual perspective taking in
      healthy adults by training participants to either imitate or to inhibit
      imitation. Twenty-four hours after training, all participants completed tests of
      ToM and visual perspective taking. The group trained to inhibit their tendency to
      imitate showed improved performance on the visual perspective-taking test, but
      not the ToM test. Neither imitation training, nor general inhibition training,
      had this effect. These results support a novel theory of social cognition
      suggesting that the same self-other discrimination process underlies imitation
      inhibition and perspective taking. Imitation, perspective taking and ToM are all
      pro-social processes--ways in which we reach out to others. Therefore, it is
      striking that perspective taking can be enhanced by suppressing imitation; to
      understand another, sometimes we need, not to get closer, but to pull away.

PMID- 22133628
TI  - Hemispheric asymmetries and cognitive flexibility: an ERP and sLORETA study.
AB  - Although functional cerebral asymmetries (FCAs) affect all cognitive domains,
      their modulation of the efficacy of specific executive functions is largely
      unexplored. In the present study, we used a lateralized version of the task
      switching paradigm to investigate the relevance of hemispheric asymmetries for
      cognitive control processes. Words were tachistoscopically presented in the left
      (LVF) and right visual half field (RVF). Participants had to categorise the words
      either based on their initial letters, or according to their word type. On half
      of the trials the task changed (switch trials) whereas on the other half it
      stayed the same (repeat trials). ERPs were recorded and the neural sources of the
      ERPs were reconstructed using standardised low resolution brain electromagnetic
      tomography (sLORETA). In the word type task, participants were faster on repeat
      trials when stimuli were presented in the RVF. In contrast, in the initial letter
      task participants were faster on repeat trials and in general more accurate after
      stimulus presentation in the LVF. In both tasks, no hemispheric asymmetries in
      reaction times were observed on switch trials. On the electrophysiological level,
      we observed a left lateralization of the N1 that was mediated by activation in
      the left extrastriate cortex as well as a greater positivity of the P3b after
      stimulus presentation in the RVF compared to the LVF that was mediated by
      activation in the superior parietal cortex. These results show that FCAs affect
      the neurophysiological correlates of executive functions related to task
      switching. The relation of neurophysiological and behavioural asymmetries is
      mediated by task complexity, with more complex tasks leading to more
      interhemispheric interaction and smaller left-right differences in behavioural
      measures. These findings reveal that FCAs are an important modulator of executive
      functions related to cognitive flexibility.

PMID- 22133631
TI  - Discovery of cyclic amine-substituted benzoic acids as PPARalpha agonists.
AB  - A series of novel cyclic amine-substituted benzoic acid derivatives were
      synthesized and evaluated for their PPARalpha agonist activity. Strucure-activity
      relationship studies led to the identification of (S)-3-[3-[2-(4-chlorophenyl)-4
      methylthyazole-5-carboxamido]piperidin-1-yl]benzoic acid (S)-4f (KRP-105) as a
      potent and high subtype-selective human PPARalpha agonist. (S)-4f showed
      excellent PK profile and oral administration of (S)-4f to high-fat diet dogs
      effectively lowered triglycerides.

PMID- 22133630
TI  - Synthesis of [18F]-labeled (2-(2-fluoroethoxy)ethyl)triphenylphosphonium cation
      as a potential agent for myocardial imaging using positron emission tomography.
AB  - [(18)F]-labeled molecular probe for the detection of myocardial perfusion deficit
      is driving particular interest due to its high clinical applicability. Thus, we
      synthesized (2-(2-[(18)F]fluoroethoxy)ethyl)triphenylphosphonium salt ([(18)F]3)
      that specifically accumulates in myocardium according to mitochondrial membrane
      potential. Here, we evaluated the performance of [(18)F]3 as a mitochondrial
      voltage sensor in vitro and in vivo. The [(18)F]3 was synthesized with 20~30%
      radiochemical yield and radiochemical purity was >98% by analytical HPLC.
      Specific activity was >6.7TBq/MUmol. The cellular uptake assay showed
      preferential uptake of [(18)F]3 in cardiomyocytes. The results of biodistribution
      and micro-PET imaging studies of [(18)F]3 in mice and rats showed preferential
      accumulation in the myocardium. The results suggest that this compound would be a
      promising candidate for myocardial imaging.

PMID- 22133629
TI  - Fluorescence detection of single nucleotide polymorphisms using nucleic acid
      probe containing tricyclic base-linked acyclonucleoside.
AB  - A reliable and simple method for detecting nucleobase mutations is very important
      clinically because sequence variations in human DNA cause genetic diseases and
      genetically influenced traits. A majority of sequence variations are attributed
      to single nucleotide polymorphisms (SNPs). Here, we developed a method for SNP
      detection using DNA probes that contained a fluorescent tricyclic base-linked
      acyclonucleoside N. The type of nucleobases involved in the SNP sites in an RNA
      target could be determined using four DNA probes containing N. Further, we found
      that the SNP in the RNA target could be detected by a visible color. Thus, this
      system would provide a novel and simple method for detecting SNPs in an RNA
      target.

PMID- 22133632
TI  - The molecular mechanisms of gap junction remodeling.

PMID- 22133633
TI  - MK-801 induces a low intensity conditioned taste aversion.
AB  - N-methyl-D-aspartate (NMDA) receptor antagonists are often used to assess the
      role of NMDA receptors in learning and memory processes. However, few studies
      have explored the possibility that the antagonists may induce a conditioned
      aversion when administered following flavor consumption. We report five
      experiments with rats intended to evaluate the MK-801 capacity to induce
      conditioned taste aversion. Our findings suggest that: i) MK-801 produces a low
      intensity aversion following repeated pairings with saccharin (Experiments 1 and
      2); ii) such aversion was not the result of a non-associative process (Experiment
      3); and iii) pre-exposure to MK-801 does not interact with conditioned taste
      aversion induced by lithium chloride (Experiments 4 and 5). These findings
      suggest that MK-801 induces a low-intensity aversion, although the underlying
      mechanisms of this aversion may differ from those of a conditioned aversion
      produced by lithium chloride.

PMID- 22133634
TI  - Nitric oxide in the nucleus accumbens is involved in retrieval of inhibitory
      avoidance memory by nicotine.
AB  - In the present study, the possible effect of nitric oxide agents injected into
      the nucleus accumbens (NAc) in the presence or absence of nicotine on morphine
      state-dependent memory in adult male Wistar rats was investigated. As a model of
      memory, a step-through type inhibitory avoidance task was used. Post-training
      injection of morphine (4 and 6mg/kg) dose dependently induced the impairment of
      memory retention. Administration of morphine (4 and 6mg/kg) before retention
      induced state-dependent retrieval of the memory acquired under post-training
      morphine (6mg/kg) influence. Injection of nicotine before retention (0.25 and
      0.5mg/kg) alone and nicotine (0.1, 0.25 and 0.5mg/kg) plus an ineffective dose of
      morphine (2mg/kg) reversed the post-training morphine-induced memory impairment.
      The amnesia elicited by morphine (6mg/kg) was also prevented by pre-retention
      intra-NAc administration of a nitric oxide synthase (NOS) inhibitor, l-NAME
      (0.24MUg/rat, intra-NAc). Interestingly, an ineffective dose of nicotine
      (0.1mg/kg) in combination with low doses of l-NAME (0.06 and 0.12MUg/rat, intra
      NAc) synergistically improved memory performance impaired by morphine given after
      training. It is important to note that intra-NAc administration of l-NAME before
      retention impaired memory retrieval by itself. In contrast, pre-retention
      administration of l-arginine, a nitric oxide (NO) precursor (0.25 and 0.5MUg/rat,
      intra-NAc), which had no effect alone, prevented the nicotine reversal of
      morphine effect on memory. The results suggest a possible role for nitric oxide
      of nucleus accumbens in the improving effect of nicotine on the morphine-induced
      amnesia and morphine state-dependent memory.

PMID- 22133635
TI  - Effects of the anandamide uptake blocker AM404 on food intake depend on feeding
      status and route of administration.
AB  - Endocannabinoids (anandamide and 2-AG) are relevant modulators of appetite and
      energy expenditure through their action on cannabinoid CB(1) receptors. The
      actions of anandamide on feeding behavior are dependent both, on the anatomical
      location of CB(1) receptors (central nervous system versus peripheral tissues)
      and the feeding status. Anandamide uptake into cells, prior to its degradation by
      specific enzymatic systems, is a necessary step for the regulation of its
      extracellular levels. The present study explores the route and feeding stimulus
      dependency of the effects of the anandamide uptake blocker AM404. Peripherally,
      AM404 reduced feeding in partially satiated animals through a PPARalpha
      independent mechanism, but not in food deprived ones. When AM404 was injected
      into the cerebral ventricles of food deprived rats, it resulted in hyperphagia
      that was antagonized by the cannabinoid receptor inverse agonist SR141716A. These
      results support the multimodal action of endocannabinoid signaling in feeding
      regulation, which depends on the anatomical site and the feeding status of the
      animal.

PMID- 22133636
TI  - Reactive oxygen species target specific tryptophan site in the mitochondrial ATP
      synthase.
AB  - The release of reactive oxygen species (ROS) as side products of aerobic
      metabolism in the mitochondria is an unavoidable consequence. As the capacity of
      organisms to deal with this exposure declines with age, accumulation of molecular
      damage caused by ROS has been defined as one of the central events during the
      ageing process in biological systems as well as in numerous diseases such as
      Alzheimer's and Parkinson's Dementia. In the filamentous fungus Podospora
      anserina, an ageing model with a clear defined mitochondrial etiology of ageing,
      in addition to the mitochondrial aconitase the ATP synthase alpha subunit was
      defined recently as a hot spot for oxidative modifications induced by ROS. In
      this report we show, that this reactivity is not randomly distributed over the
      ATP Synthase, but is channeled to a single tryptophan residue 503. This residue
      serves as an intra-molecular quencher for oxidative species and might also be
      involved in the metabolic perception of oxidative stress or regulation of enzyme
      activity. A putative metal binding site in the proximity of this tryptophan
      residue appears to be crucial for the molecular mechanism for the selective
      targeting of oxidative damage.

PMID- 22133637
TI  - Electrogenic events upon photolysis of CO from fully reduced cytochrome c
      oxidase.
AB  - CO photolysis from fully reduced Paracoccus denitrificans aa(3)-type cytochrome c
      oxidase in the absence of O(2) was studied by time-resolved potential
      electrometry. Surprisingly, photo dissociation of the uncharged carbon monoxide
      results in generation of a small-amplitude electric potential with the same sign
      as the physiological charge separation during activity. The number of
      electrogenic events after CO photolysis depends on the state of the enzyme. CO
      photolysis following immediately after activation by an enzymatic turnover,
      showed a two-component potential development. A fast (~1.5MUs) phase was followed
      by slower potential generation with a time constant varying from 8MUs at pH 7 to
      250MUs at pH 10. The amplitude of the fast phase was independent of the time of
      incubation after enzyme activation, whereas the slower phase vanished with a time
      constant of ~25min. CO photolysis from enzyme that had not undergone a prior
      single turnover showed the fast phase, but the amplitude of the slow phase was
      reduced to 10-30%. The amplitude of the fast phase corresponds to charge movement
      of 0.83A perpendicular to the membrane dielectric, and is independent of the time
      after enzyme activation. Thus it can be used as an internal ruler for
      normalization of the electrogenic responses of CcO. The slow phase was absent in
      the K354M mutant with a blocked proton-conducting K channel. We propose that CO
      photolysis increases the pK of the K354 residue, which results in its partial
      protonation, and generation of electric potential.

PMID- 22133638
TI  - Methylation of microRNA-9 is a specific and sensitive biomarker for oral and
      oropharyngeal squamous cell carcinomas.
AB  - Detection of DNA methylation has produced promising results as biomarkers for
      head and neck squamous cell carcinoma (HNSCC). However, current panels are
      limited by an insufficient number of sensitive and specific tumor markers.
      MicroRNAs (miR) play an important role in tumorigenesis, and may represent a
      novel panel of molecules for the development of cancer biomarkers. We
      investigated methylation of three miRNA promoter sites of miR-9 (miR-9-1, miR-9
      2, miR-9-3) in 107 human head and neck tissue samples and controls. We found
      methylations of miR-9-1 and miR-9-3 were higher in oral and oropharyngeal
      carcinomas than that in laryngeal carcinoma, achieving a combined sensitivity of
      63% and 56%, respectively, for these two tumor types, compared to 21% for the
      laryngeal carcinoma. Quantitative PCR of miR-9 showed reduced expression
      associated with methylation of miR-9 in tumor tissues. To investigate the
      functional consequences of miR-9 methylation, we found that miR-9 methylation is
      correlated with miR-9 expression level in human HNSCC cell lines. Demethylation
      treatment using 5-aza-deoxycytidine restored its expression in a miR-9 methylated
      human HNSCC cell line UM-SCC22A. Furthermore, cell proliferation and viability
      was significantly inhibited, while PTEN expression was elevated after
      transfection of miR-9 into the UM-SCC22A cell line. In summary, our results
      suggest that methylations of miR-9-1 and miR-9-3 are sensitive and specific
      biomarkers for HNSCC, particularly for oral and oropharyngeal squamous cell
      carcinomas. In addition, miR-9 may function as a tumor suppressor in HNSCC
      through inhibition of cell proliferation and elevation of tumor suppressor PTEN.

PMID- 22133639
TI  - Intermediate-term efficacy of Tm:YAG laser prostate vaporesection for bladder
      outlet obstruction: initial experience from a UK teaching hospital.
AB  - OBJECTIVES: To assess the safety and clinical efficacy of Tm:YAG laser
      vaporesection of the prostate (ThuVaRP) at intermediate-term follow-up. PATIENTS
      AND METHODS: We identified the first 60 consecutive patients who underwent
      ThuVaRP at our institute. Operative outcomes assessed were resection time,
      resection weight, drop in haemoglobin, transfusion rate, catheter time and
      complication rate. The International Prostate Symptom Score (IPSS) was documented
      at a mean follow-up period of 19 months postoperatively. RESULTS: 45/60 patients
      underwent treatment due to lower urinary tract symptoms secondary to benign
      prostatic obstruction, 11/60 patients had a long-term catheter in situ for
      refractory urinary retention secondary to benign prostatic obstruction, and 4/60
      patients had bladder outflow obstruction secondary to adenocarcinoma of the
      prostate. 1/60 patients developed urosepsis, 1/60 patients developed a urinary
      tract infection and 1/60 patients required 3-way catheterization and irrigation
      due to haematuria. No patients required a blood transfusion. The mean IPSS at a
      mean follow-up interval of 19 months (range 15-28 months) was 5.1 (range 1-23).
      Postoperative maximum flow rate improved from 7.9 to 17.1 ml/s, and post
      micturition residual volume decreased from 254 to 86 ml. CONCLUSION: ThuVaRP is
      safe and appears to have durable efficacy at intermediate follow-up.

PMID- 22133640
TI  - Interatomic potential for uranium in a wide range of pressures and temperatures.
AB  - Using the force-matching method we develop an interatomic potential that allows
      us to study the structure and properties of alpha-U, gamma-U and liquid uranium.
      The potential is fitted to the forces, energies and stresses obtained from ab
      initio calculations. The model gives a good comparison with the experimental and
      ab initio data for the lattice constants of alpha-U and gamma-U, the elastic
      constants, the room-temperature isotherm, the normal density isochore, the bond
      angle distribution functions and the vacancy formation energies. The calculated
      melting line of uranium at pressures up to 80 GPa and the temperature of the
      alpha-gamma transition at 3 GPa agree well with the experimental phase diagram of
      uranium.

PMID- 22133641
TI  - Anti-leukemic activity of Newcastle disease virus strains AF2240 and V4-UPM in
      murine myelomonocytic leukemia in vivo.
AB  - Newcastle disease virus (NDV) is a member of the Paramyxoviridae that has caused
      severe economic losses in poultry industry worldwide. Several strains of NDV were
      reported to induce cytolysis to cancerous cell lines. It has prompted much
      interest as anticancer agent because it can replicate up to 10,000 times better
      in human cancer cells than in most normal cells. In this study, two NDV strains,
      viserotropic-velogenic strain AF2240 and lentogenic strain V4-UPM, showed
      cytolytic activity and apoptosis induction against Mouse myelomoncytic leukemia
      (WEHI 3B). The cytolytic effects of NDV strains were determined using
      microtetrazolium (MTT) assay. The cytolytic dose - fifty percent (CD(50)) were 2
      and 8HAU for AF2240 and V4-UPM strains, respectively. Cells treated with NDV
      strains showed apoptotic features compared to the untreated cells under
      fluorescence microscope. NDV induced activation of caspase-3 and DNA laddering in
      agarose gel electrophoresis which confirmed the apoptosis. The anti-leukemic
      activity of both strains was evaluated on myelomoncytic leukemia BALB/c mice. The
      results indicated that both NDV strains significantly decreased liver and spleen
      weights. It also decreased blasts cell percentage in blood, bone marrow and
      spleen smears of treated mice (p<0.05). Histopathological studies for spleen and
      liver confirmed the hematological results of blood and bone marrow. From the
      results obtained, the exposure to both NDV stains AF2240 and V4-UPM showed
      similar results for Ara-c. In conclusion NDV strains AF2240 and V4-UPM can affect
      WEHI 3B leukemia cells in vitro and in vivo.

PMID- 22133642
TI  - The degree of neutropenia has a prognostic impact in low risk myelodysplastic
      syndrome.
AB  - The severity of neutropenia in myelodysplastic syndrome (MDS) has not been
      completely studied. We analyzed the prognostic significance of severe neutropenia
      (neutrophils count <0.5*10(9)/L) at diagnosis in 1109 patients with de novo MDS
      and low/intermediate-1 IPSS included in the Spanish MDS Registry. Severe
      neutropenia was present at diagnosis in 48 of 1109 (4%). Patients with severe
      neutropenia were most strongly represented within the groups of refractory
      cytopenia with multilineage dysplasia (40%) and refractory anemia with excess of
      blast type 1 (29%). Severe neutropenia had negative effects on the
      low/intermediate-1 risk group. A significant difference in overall survival was
      observed between patients with severe neutropenia (28 months) and patients with a
      neutrophil count higher than 0.5*10(9)/L (66 months) (p<0.0001). Also, severe
      neutropenia predicted a significantly reduced on leukemia-free survival
      (p<0.0001). In the multivariate analysis, severe neutropenia retained its
      independent prognostic influence on overall survival [HR: 2.19, 95% CI (1.41
      3.10), p<0.0001] and leukemia free survival [HR: 3.51, 95% CI (1.97-6.26),
      p<0.0001]. The degree of neutropenia should be considered as additional
      prognostic factor in low/intermediate-1 IPSS MDS.

PMID- 22133643
TI  - Fibrinolytic treatment of acute ischemic stroke for patients on new oral
      anticoagulant drugs.

PMID- 22133645
TI  - Toward better teamwork: recommendations for improved integration of epidemiology
      and risk assessment.

PMID- 22133644
TI  - Bauer ketones 23 and 24 from Echinacea paradoxa var. paradoxa inhibit
      lipopolysaccharide-induced nitric oxide, prostaglandin E2 and cytokines in
      RAW264.7 mouse macrophages.
AB  - Among the nine Echinacea species, E. purpurea, E. angustifolia and E. pallida,
      have been widely used to treat the common cold, flu and other infections. In this
      study, ethanol extracts of these three Echinacea species and E. paradoxa,
      including its typical variety, E. paradoxa var. paradoxa, were screened in
      lipopolysaccharide (LPS)-stimulated macrophage cells to assess potential anti
      inflammatory activity. E. paradoxa var. paradoxa, rich in
      polyenes/polyacetylenes, was an especially efficient inhibitor of LPS-induced
      production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1 beta (IL
      1beta) and interleukin-6 (IL-6) by 46%, 32%, 53% and 26%, respectively, when
      tested at 20 MUg/ml in comparison to DMSO control. By bioactivity-guided
      fractionation, pentadeca-8Z-ene-11, 13-diyn-2-one (Bauer ketone 23) and pentadeca
      8Z, 13Z-dien-11-yn-2-one (Bauer ketone 24) from E. paradoxa var. paradoxa were
      found primarily responsible for inhibitory effects on NO and PGE2 production.
      Moreover, Bauer ketone 24 was the major contributor to inhibition of inflammatory
      cytokine production in LPS-induced mouse macrophage cells. These results provide
      a rationale for exploring the medicinal effects of the Bauer ketone-rich taxon,
      E. paradoxa var. paradoxa, and confirm the anti-inflammatory properties of Bauer
      ketones 23 and 24.

PMID- 22133646
TI  - Identification procedures as a part of death investigation in Turkey.
AB  - Forensic identification techniques include the examination of ID cards, the
      decedent's private belongings, fingerprints, footprints, lip marks, dental
      findings, red blood cell enzymes, performing photograph matching, facial
      reconstruction, visual identification, and DNA "fingerprinting." As part of
      forensic examinations, the identification of corpses that are fresh, decomposed,
      fragmented, or skeletonized as well as individual body parts and human remains
      can be requested. Identification becomes a challenging task for forensic terms
      particularly in mass-disaster situations. Each identification case should be
      considered to its own merit and the way to do that should be based on the
      effectiveness and cost of each method used. In Turkey, one of the major duties of
      the medicolegal system on the investigation of deaths is to identify the deceased
      if unknown.This study is undertaken to investigate the procedures, as well as
      their validities, used to deal with individualization of dismembered bodies
      directly sent to the Council of Forensic Medicine, Ministry of Justice, for
      autopsy and/or visual identification, as well as those received from peripheral
      districts for forensic identification. According to the Turkish Penal Procedural
      Law, a positive identification of the deceased is mandatory before performing an
      autopsy. According to the law, the ID cards are not taken to be sufficient for
      recognition of the deceased, and the major way of identification in daily
      practice is visual identification by a relative or any recognizant person to
      approve the identification to the prosecutor. If visual identification fails,
      fingerprints, dental x-rays or body x-rays, and DNA "fingerprinting" can be used
      to establish identity when compared with known records of the individual obtained
      by law enforcement.This retrospective study was carried out into 421 dismembered
      bodies, among 3063 autopsies performed in year 2002 by the Department of Morgue
      at the Council of Forensic Medicine, with particular insight into the
      identification procedures undertaken and their results. The overall negative
      identification rate was 30.4%, and in 1% of the cases, the visual identification
      by relatives were not confirmed by DNA identification and taken as misidentified.

PMID- 22133647
TI  - Acceleration of neutrophil precursors' maturation and immunostimulation of CD3+,
      CD4+ lymphocytes by stanozolol in mice.
AB  - The abuse of anabolic-androgenic steroids (AAS) for improved physical performance
      is associated with many deleterious effects. The present study aims to evaluate
      the short-term effect of an AAS compound stanozolol, on lipoprotein profile,
      granulopoiesis and immune response in adult female mice. The mice were assigned
      to five experimental groups and different doses of stanozolol (low - 0.05 mg,
      medium - 0.5 mg, high - 5 mg and highest dose - 7.5 mg/kg bwt or only vehicle
      respectively) were administered s.c. for 15 days. A decrease in high density
      lipoprotein cholesterol (HDL-c) as well as total cholesterol (TC) in all the
      stanozolol treated groups and an increase in low density lipoprotein (LDL-c) in
      high and the highest dose treated groups indicate that stanozolol alters serum
      lipoprotein profile. A significant increase in the percentage of myelocytes,
      metamyelocytes and neutrophils in all the treated mice unveils the stimulation of
      granulopoiesis through the acceleration of neutrophil precursors' maturation in
      the bone marrow of mice. The stimulation of erythropoiesis was also noted in all
      the treated groups. The flow cytometry analysis of lymphocyte subpopulations
      (CD3(+) and CD4(+)) revealed immunoenhancing response of stanozolol at optimum
      physiological dose, however, it is immunosuppressive at supraphysiologic level.
      We conclude that stanozolol accelerates granulopoiesis and stimulates immune
      response (at physiologic level only), though it alters the lipoprotein profile in
      mice.

PMID- 22133649
TI  - The association between functional health literacy and patient-reported recall of
      medications at outpatient pharmacies.
AB  - BACKGROUND: Published literature on assessing the functional health literacy
      (FHL) level of patients in pharmacy practice is lacking. OBJECTIVES: To assess
      FHL in an outpatient pharmacy setting and the associations between FHL and
      patient recall of medications. METHODS: In a cross-sectional study of 79 English
      speaking adults recruited from 3 outpatient pharmacies, patients were given the
      Short Test of Functional Health Literacy in Adults and asked to recall their
      medication names, dosages, frequencies, and indications. Patients' responses were
      compared with pharmacy records (medication name, dosage, frequency) and Facts and
      Comparisons (indication). RESULTS: Of the 79 patients, 27 had inadequate FHL.
      Correct medication names were recalled less frequently by patients with
      inadequate FHL compared with patients with adequate FHL (60% vs 84%, P<.001).
      Similarly, correct dosages (71% vs 83%, P=.03) and frequencies (62% vs 85%,
      P<.001) were reported less often by patients with inadequate FHL. There was no
      significant difference in the frequency of correct indications for medications
      between the 2 groups. CONCLUSIONS: Inadequate FHL is associated with poor recall
      of correct medication name, dosage, and administering frequency. Future research
      to evaluate the effect of pharmacists on improving patients' recall of medication
      name, dosage, and frequency is warranted.

PMID- 22133651
TI  - Incidence of lower limb amputations in individuals with and without diabetes
      mellitus in Andalusia (Spain) from 1998 to 2006.
AB  - AIMS: We studied the changes in the incidence of lower limb amputation (LLA) in
      Andalusia from 1998 to 2006 in the population with and without diabetes. METHODS:
      We undertook a retrospective study of all LLA performed in Andalusia in people
      aged 30 years old, with or without diabetes, between 1 January 1998 and 31
      December 2006. We obtained the crude and standardized incidence rates by year,
      and sex for three periods: 1998-2000, 2001-2003 and 2004-2006 and calculated the
      RR of requiring LLA in patients with diabetes. To test for time trend, Poisson
      regression models were fitted. RESULTS: A total of 16,210 LLA were carried out in
      Andalusia, 72.6% in patients with diabetes mellitus and 66.4% in men. In the
      population with diabetes the standardized incidence of all LLA was found to be
      344.0 per 100,000 (95% CI, 315.4-372.4) in 2004-2006. There was an estimated
      incidence increase for all LLA by 14% and for minor LLA by 13.6% in 2004-2006. In
      people with diabetes the RR increased by 31.6% as compared to the first period.
      CONCLUSIONS: Despite the implementation of a care plan for patients with
      diabetes, the incidence of LLA has not fallen in Andalusia in recent years.

PMID- 22133650
TI  - Identifying iatrogenic depression using confirmatory factor analysis of the
      Center for Epidemiologic Studies Depression Scale in patients prescribed a
      verapamil-sustained-release-led or atenolol-led hypertension treatment strategy.
AB  - BACKGROUND: beta-blockers and calcium channel blockers are highly effective
      medications indicated for treatment and prevention of hypertension. However, the
      literature regarding the potential depressive effects of beta-blockers and
      calcium channel blockers is equivocal regarding whether one or both are
      associated with depression. OBJECTIVES: To determine whether self-reported
      depressive symptoms of older persons with hypertension and coronary artery
      disease and who were randomly assigned to a verapamil-sustained-release-led (Ve
      led) or atenolol-led (At-led) hypertension treatment strategy were similar using
      confirmatory factor analytical models of the Center for Epidemiologic Studies
      Depression Scale (CES-D). METHODS: This study used a mail survey of patients
      enrolled in a substudy of an international randomized controlled clinical trial.
      Complete data on the CES-D after 1 year of treatment were obtained from 1019
      study subjects. Multiple group confirmatory factor analysis (CFA) procedures were
      used to test for differences in the fit of the data to the initial 4-factor CES-D
      model among patients assigned to the 2 treatment groups after 12 months of
      therapy. A test of configural invariance was conducted by sequentially
      constraining various matrices to be equal across groups. The convergent validity
      of the model was tested by examining the standard errors of the lambda-X
      parameter estimates of the configural model. The factor loadings for like items
      were investigated across the 2 groups using a test of strong factorial
      invariance. Finally, the 2 treatment groups were compared on the 4 factors to
      detect differences in the model's parameters. RESULTS: Overall, the data fit the
      CFA models across the 2 treatment groups based on the 4-factor model. However, 3
      items differed slightly, including appetite, depressed, and crying. The data
      suggested significant differences across groups on the positive affect,
      interpersonal relations, and somatic and retarded activity latent variables.
      CONCLUSIONS: The domains indicating less happiness and more depressive symptoms
      were most likely to be unfavorably impacted by the At-led treatment strategy.
      Given a choice between these equally effective high blood pressure treatment
      strategies, it may be prudent to use the Ve-led strategy. This is especially true
      if the risk of the occurrence of a mood-related side effect of the beta-blocker
      outweighs its other benefits in comparison.

PMID- 22133652
TI  - Disturbance of B-vitamin status in people with type 2 diabetes in Indonesia--link
      to renal status, glycemic control and vascular inflammation.
AB  - BACKGROUND: Diabetes is associated with mishandling of thiamine in the kidney and
      development of diabetic nephropathy. The aim of this study is to assess the
      disturbance of thiamine and other B-vitamin status of patients with type 2
      diabetes in Indonesia. METHODS: One hundred and fifteen patients with type 2
      diabetes with and without microalbuminuria or albuminuria and 39 healthy people
      were recruited. After a 2-month washout period for B-vitamin supplementation,
      markers of vitamins B(1), B(6), B(9) and B(12), were determined. RESULTS:
      Fractional excretion of thiamine (22.8 versus 33.5%; P<0.05) and urinary
      excretion of the vitamin B(6) degradation product 4-pyridoxic acid (0.081 versus
      0.133 MUmol/g creatinine, P<0.001) was increased in patients with type 2 diabetes
      with respect to healthy controls. There was also increased total plasma cobalamin
      (398 versus 547 pmol/l, P<0.001) and holotranscobalamin (74 versus 97 pmol/l,
      P<0.001) in patients with type 2 diabetes. In multiple regression analysis these
      were linked to HbA1c, duration of diabetes and systolic blood pressure, and
      fasting plasma glucose, folate and C-reactive protein, respectively. CONCLUSIONS:
      There was renal mishandling of thiamine, increased degradation of vitamin B(6)
      and cytosolic metabolic resistance to vitamin B(12) in patients with type 2
      diabetes in Indonesia.

PMID- 22133653
TI  - The localisation of HSP70 and oxidative stress indices in heads of Spodoptera
      exigua larvae in a cadmium-exposed population.
AB  - The effects of cadmium toxicity may vary between animals with different history
      of metal exposure. The aim of our study was to examine HSP70, protein carbonyl
      levels, catalase activity and total antioxidant capacity in the heads of
      Spodoptera exigua (Hubner) larvae originated from undergoing 1- and 44
      generational cadmium treatment and in control (those that were not exposed to
      cadmium). We also measured the cadmium concentration and DNA damage level in the
      larvae. We observed higher level of heat shock proteins (HSPs) in the heads of
      larvae derived from multi-generational metal treatment than in the heads of those
      from one-generational treatment (derived from the control rearing). Analysis of
      HSP localisation in the larval brain suggests that these changes could be
      important for protecting the neural function of larval mushroom bodies for
      animals selected during multigenerational metal exposure. Animals from one
      generational treatment had, in turn, higher total antioxidant capacity than
      animals from multigenerational treatment. Anyway, animals from one- and 44
      generational metal treatments did not differ in metal accumulation in the heads
      and the whole larval bodies, catalase activity or DNA damage level. All these
      measurements were higher than for control larvae and cadmium accumulation in the
      heads was much lower than in the whole bodies.

PMID- 22133654
TI  - Quantitative muscle ultrasound is a promising longitudinal follow-up tool in
      Duchenne muscular dystrophy.
AB  - Responsive outcome measures are needed to follow the disease status of Duchenne
      muscular dystrophy (DMD) patients, as new therapeutic approaches become available
      for affected boys. Quantitative muscle ultrasound (QMUS) is potentially an
      attractive follow up tool for DMD because it reflects the severity of the
      dystrophic process without the need for invasive procedures, by quantifying echo
      intensity (i.e., mean grey level of muscle images) and muscle thickness. We
      performed a longitudinal follow-up of lower and upper extremity QMUS in 18 DMD
      patients and compared this with physical functioning in 11 of these patients.
      QMUS could be performed in every patient, and no patient was subjected to more
      than a total of 20min of ultrasound scanning time for this study. As expected we
      found a significant increase of echo intensity with age, reflecting increasing
      dystrophic muscle changes. This increase was related to ambulatory status,
      functional grading, muscle strength and motor ability. Our study establishes QMUS
      as a practical and child-friendly tool for the longitudinal follow up of DMD
      patients.

PMID- 22133655
TI  - Clinical features and new molecular findings in muscle phosphofructokinase
      deficiency (GSD type VII).
AB  - Muscle phosphofructokinase (PFKM) deficiency, a rare disorder of glycogen
      metabolism also known as glycogen storage disease type VII (GSDVII), is
      characterized by exercise intolerance, myalgias, cramps and episodic
      myoglobinuria associated with compensated hemolytic anaemia and hyperuricemia. We
      studied five patients with PFKM deficiency coming from different Italian regions.
      All probands showed exercise intolerance, hyperCKemia, cramps and myoglobinuria.
      One patient had a mild hypertrophic cardiomyopathy. Biochemical studies revealed
      residual PFK activity ranging from 1 to 5%. Molecular genetic analysis identified
      four novel mutations in the PFKM gene. In our series of patients, clinical and
      laboratory features were similar in all but one patient, who had an unusual
      phenotype characterized by 25 ears disease history, high CK levels, hypertrophic
      cardiomyopathy with paroxysmal atrial fibrillation without fixed muscle weakness.

PMID- 22133656
TI  - The effect of perioperative ketorolac on pain control in pregnancy termination.
AB  - BACKGROUND: The study was conducted to evaluate the effect of perioperative
      ketorolac on pain associated with first-trimester aspiration abortion. STUDY
      DESIGN: A double-blind, randomized, placebo-controlled trial was performed
      involving pregnant women up to 14 weeks' gestation who desired pregnancy
      termination. Subjects were randomized to receive ketorolac 30 mg intravenously
      (n=31) or placebo (n=45) at the time of induction of anesthesia. Postoperative
      pain was assessed using a visual analog scale (VAS). The primary outcome was pain
      control as determined by VAS score. Secondary measures of patient use of
      supplemental postoperative pain medications and patient satisfaction were
      assessed. RESULTS: Subjects in the ketorolac group had lower postoperative pain
      scores on the VAS at all time points compared to the placebo group, but the
      difference was not statistically significant. The ketorolac group used less
      postoperative acetaminophen compared to the placebo group (6.5% versus 35.6%),
      respectively. Subjects in the placebo group and the ketorolac group had similar
      requirements for postoperative narcotics in the recovery room (22.2% versus
      19.4%). Patient satisfaction with pain level was equivalent between the groups at
      all postoperative end points. There was no observed difference in perioperative
      blood loss observed between the two groups. CONCLUSION: Perioperative ketorolac
      has the same effect on postoperative pain as determined by VAS as placebo. The
      use of ketorolac at the 30-mg dose cannot be recommended for better pain control
      for patients undergoing first-trimester pregnancy termination by suction
      curettage. The only positive effect of the use of ketorolac compared to placebo
      was a reduction in the use of acetaminophen. Ketorolac use does not appear to
      change blood loss in the operating room or through postoperative day 1 compared
      to placebo.

PMID- 22133657
TI  - Contraceptive sterilization among married adults: national data on who chooses
      vasectomy and tubal sterilization.
AB  - BACKGROUND: Vasectomy has been found to be a highly cost-effective contraceptive
      method. For couples, tubal sterilization and vasectomy have the same result, but
      the two methods are used by different segments of the population. STUDY DESIGN:
      We conducted an analysis of data from male and female samples of the 2006-2008
      National Survey of Family Growth, nationally representative samples of men and
      women in the United States aged 15-44 years. RESULTS: Among married men, 13.1%
      reported vasectomies (95% confidence interval 10.4%-16.3%), compared to 21.1%
      (17.8%-24.9%) of married women who reported tubal sterilizations. Men with higher
      education and income had greater prevalence of vasectomy than those less
      educated, while women with lower education and income had the highest prevalence
      of tubal sterilization. CONCLUSIONS: Efforts to promote vasectomy use need to
      understand the reasons behind these differences. Increasing the availability and
      use of vasectomy will require education about its benefits.

PMID- 22133658
TI  - Characteristics of presumptive idiopathic disseminated intravascular coagulation
      during second-trimester induced abortion.
AB  - BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious and
      relatively uncommon complication of induced or spontaneous abortion or delivery.
      Occasionally, it has been reported in the absence of predisposing conditions.
      Little information in the literature describing idiopathic DIC or the treatment
      of patients with DIC exists. STUDY DESIGN: From 2002 through 2008, 24 cases of
      presumptive idiopathic DIC occurred following dilation and evacuation (D&E)
      abortion between 13 5/7 and 23 6/7 weeks' estimated gestational age at a
      Midwestern ambulatory surgical center. The characteristics of each patient, their
      pregnancies and surgical experiences were examined and compared with a temporally
      matched control group of D&E patients. We explored whether the index cases had a
      predominance of any historical, clinical or reproductive characteristics compared
      with controls matched for demographic and reproductive landmarks. RESULTS:
      Overall incidence of presumptive idiopathic DIC was 1.8 per 1000 D&E cases.
      Compared with matched controls, there was a greater likelihood of DIC with more
      advanced gestation (p=.009); no case of DIC was under 17 weeks' gestational age.
      Increased bleeding occurred at a mean time of 153 min after completion of surgery
      (range, 55-491 min; median, 131 min). Nineteen of 24 cases were successfully
      treated at the surgical center after receiving 6 to 8 units of fresh-frozen
      plasma (FFP); 5 cases were transferred to a hospital for further treatment.
      CONCLUSIONS: The abnormal bleeding of presumptive DIC typically begins to appear
      within 2 h after uncomplicated D&E and is more likely to occur at 17 weeks'
      estimated gestational age and more. With rapid diagnosis and treatment, most
      patients were able to be treated in an outpatient setting with up to 6 to 8 units
      of FFP and rehydration.

PMID- 22133660
TI  - Ethinyl estradiol and levonorgestrel pharmacokinetics with a low-dose transdermal
      contraceptive delivery system, AG200-15: a randomized controlled trial.
AB  - BACKGROUND: This study evaluated the ethinyl estradiol (EE) and levonorgestrel
      (LNG) pharmacokinetic profiles of AG200-15, a transdermal contraceptive delivery
      system, compared with a combination oral contraceptive (COC) containing EE 35 mcg
      and norgestimate 250 mcg. STUDY DESIGN: A Phase 1, open-label, single-center
      study in 36 healthy women was conducted over three cycles with a randomized
      crossover design. After a run-in cycle of 21 days on and 7 days off with AG200
      15, participants were randomized to receive one of two treatments: a 21/7-day
      cycle of AG200-15 either followed or preceded by one cycle of the COC. This trial
      is registered on ClinicalTrials.gov under the identifier NCT01243580. RESULTS:
      During the third week of AG200-15 use, mean (+/-standard deviation) maximum serum
      concentration (C(max)), area under the curve(0-168 h) and steady-state
      concentration (C(ss48-168 h)) for EE were 51.3 +/- 17.3 pg/mL, 6.26 +/- 2.46 ng
      h/mL and 35.7 +/- 14.5 pg/mL, respectively; for LNG, the corresponding values
      were 2400 +/- 1140 pg/mL, 317 +/- 159 ng h/mL and 1847 +/- 930 pg/mL,
      respectively. The AG200-15 EE C(max) was approximately 60% lower and the EE C(ss)
      was 15%-20% lower than those obtained with the COC. The calculated daily dose of
      AG200-15 was equivalent to a 30-mcg EE COC. The most common adverse events (AEs;
      >10%) in the AG200-15 group were headache, nausea and application-site
      irritation. All drug-related AEs were mild, and no serious AEs were reported.
      CONCLUSIONS: EE and LNG daily exposure during AG200-15 treatment was within the
      range reported for a low-dose COC. The daily EE dose with AG 200-15 was
      equivalent to a 30-mcg COC and was safe and well tolerated.

PMID- 22133659
TI  - Magnetic resonance imaging and gynecological devices.
AB  - BACKGROUND: Performing magnetic resonance imaging (MRI) on women with
      gynecological devices is a completely accepted practice. The goal of our review
      is to assess how safe it is to perform MRI on women using contraceptive implants
      or devices. STUDY DESIGN: Literature review, searching in PubMed-Medline/Ovid for
      the following keywords: magnetic resonance imaging, intrauterine devices,
      Implanon((r)) and Essure((r)). RESULTS: Though plastic devices do not represent a
      contraindication to the use of the technique, those including metallic components
      have been submitted to several tests, after which they were classified as MR
      Conditional (devices presenting no risks in MR-specific environments) by the Food
      and Drug Administration. Thus, the use of MRI can be safely advised to women with
      this type of device as long as the magnetic resonance equipment is <=3.0 T.
      CONCLUSIONS: Presently, there is no scientific evidence that contraindicates
      performing MRI on women with any kind of gynecological device. Therefore, this
      procedure is safe as long as it is performed under previously tested conditions.

PMID- 22133662
TI  - Peripheral nerve: from the microscopic functional unit of the axon to the
      biomechanically loaded macroscopic structure.
AB  - Peripheral nerves are composed of motor and sensory axons, associated ensheathing
      Schwann cells, and organized layers of connective tissues that are in continuity
      with the tissues of the central nervous system. Nerve fiber anatomy facilitates
      conduction of electrical impulses to convey information over a distance, and the
      length of these polarized cells necessitates regulated axonal transport of
      organelles and structural proteins for normal cell function. Nerve connective
      tissues serve a protective function as the limb is subjected to the stresses of
      myriad limb positions and postures. Thus, the tissues are uniquely arranged to
      control the local nerve fiber environment and modulate physical stresses. In this
      brief review, we describe the microscopic anatomy and physiology of peripheral
      nerve and the biomechanical properties that enable nerve to withstand the
      physical stresses of everyday life.

PMID- 22133661
TI  - Relation of androgen receptor sensitivity and mood to sexual desire in hormonal
      contraception users.
AB  - BACKGROUND: Since very little research in this field is available, this study
      aims to assess the role of psychosexual, relationship, hormonal and genetic
      measures in the sexual desire of users of three hormonal contraceptive products
      [low-dose combined oral contraceptive (20 mcg ethinylestradiol/150 mcg
      desogestrel), progestin-only pill (75 mcg desogestrel) and vaginal ring (daily
      dose of 15 mcg ethinylestradiol/120 mcg etonogestrel)]. STUDY DESIGN: Fifty-five
      couples were randomized over three groups in which the women consecutively used
      each product during 3 months. Both partners repeatedly filled out questionnaires
      on solitary and dyadic sexual desire (desire to behave sexually by oneself or
      towards a partner). Total and free testosterone, sex hormone binding globulin and
      a genetic marker of androgen receptor sensitivity [cytosine-adenine-guanine (CAG)
      repeat length] were assessed on blood samples of the female partners. RESULTS:
      Sexual desire was higher in women with either short or long CAG repeats
      (solitary, p=.004; dyadic, p=.008). Desire levels were higher during vaginal ring
      use (solitary, p=.018; dyadic, p=.007). The woman's mood was found to impact her
      dyadic sexual desire (p<.001); this scale was also strongly associated with the
      male partner's dyadic sexual desire (p<.001). CONCLUSIONS: The current study
      found evidence for a role of androgen receptor sensitivity and mood in the sexual
      desire of hormonal contraceptive users.

PMID- 22133663
TI  - The Long-term relationship between duration of treatment and contracture
      resolution using dynamic orthotic devices for the stiff proximal interphalangeal
      joint: a prospective cohort study.
AB  - STUDY DESIGN: Descriptive design with a prospective cohort. INTRODUCTION: Little
      is known about the long-term relationship between the duration of treatment using
      dynamic orthoses (splints), and contracture resolution in the stiff proximal
      interphalangeal (PIP) joint. PURPOSE OF THE STUDY: To examine the long-term
      relationship between weeks of treatment using dynamic orthoses and contracture
      resolution, in both flexion and extension deficits of the PIP joint. METHODS:
      Forty-one participants were treated with a dynamic orthotic device (splint) for
      either a flexion or extension deficit of the PIP joint (n=48 joints). The
      relationship between contracture resolution and weeks of treatment was examined
      controlling for baseline range of motion (ROM), weekly total end range time,
      pretreatment joint stiffness, time since injury, and diagnosis. Outcome was
      measured via change in torque and active ROM. RESULTS: Outcome with orthotic use
      was significantly associated with the weeks of treatment (p<0.001). ROM increased
      in a linear fashion although faster progress was observed when treatment was
      aimed at improving flexion rather than extension. Flexion deficits appeared to
      maximize gains with orthotic treatment after 12 weeks. However, extension
      deficits continued to demonstrate slow and continuous improvement beyond the 17
      weeks of recorded data. Less treatment duration (in weeks) was needed to restore
      flexion than extension. CONCLUSIONS: The duration of orthotic use (weeks of
      treatment) is significantly associated with the extent of contracture resolution.
      Slower recovery of ROM and a longer duration of orthotic use may be expected when
      the treatment goal is to improve extension rather than flexion. LEVEL OF
      EVIDENCE: 2b.

PMID- 22133664
TI  - Effect of the upper limbs muscles activity on the mechanical energy gain in pole
      vaulting.
AB  - The shoulder muscles are highly solicited in pole vaulting and may afford energy
      gain. The objective of this study was to determine the bilateral muscle activity
      of the upper-limbs to explain the actions performed by the vaulter to bend the
      pole and store elastic energy. Seven experienced athletes performed 5-10 vaults
      which were recorded using two video cameras (50Hz). The mechanical energy of the
      centre of gravity (CG) was computed, while surface electromyographic (EMG)
      profiles were recorded from 5 muscles bilateral: deltoideus, infraspinatus,
      biceps brachii, triceps, and latissimus dorsi muscles. The level of intensity
      from EMG profile was retained in four sub phases between take-off (TO1) and
      complete pole straightening (PS). The athletes had a mean mechanical energy gain
      of 22% throughout the pole vault, while the intensities of deltoideus, biceps
      brachii, and latissimus dorsi muscles were sub phases-dependent (p<0.05).
      Stabilizing the glenohumeral joint (increase of deltoideus and biceps brachii
      activity) and applying a pole bending torque (increase of latissimus dorsi
      activity) required specific muscle activation. The gain in mechanical energy of
      the vaulter could be linked to an increase in muscle activation, especially from
      latissimusdorsi muscles.

PMID- 22133665
TI  - An immunostimulatory polysaccharide (SCP-IIa) from the fruit of Schisandra
      chinensis (Turcz.) Baill.
AB  - A water-soluble polysaccharide named SCP-IIa was isolated from the water extract
      of the fruit of Schisandra chinensis (Turcz.) Baill by means of ethanol
      precipitation, deproteination, anion-exchange and gel-permeation chromatography.
      The molecular weight of SCP-IIa was ascertained via HPLC, and immuno-modulating
      effect was evaluated using the immunosuppressed model induced by
      cyclophosphamide. SCP-IIa was a homogeneous form of polysaccharide, with an
      average molecular weight of approximately 7700 Da. The detected parameters showed
      that SCP-IIa increased the thymus and spleen indices, as well as the pinocytic
      activity of the peritoneal macrophages in immunosuppressed mice. The splenocyte
      proliferation assay showed that SCP-IIa, in combination with Con A or LPS,
      positively affected splenocyte proliferation. Moreover, the polysaccharide
      promoted hemolysin formation. The results suggested that SCP-IIa was involved in
      immunomodulatory effects leading to the exploration for SCP-IIa as a potential
      immunostimulant.

PMID- 22133666
TI  - Soluble endoglin and transforming growth factor-beta1 and the development of
      vasospasm after spontaneous subarachnoid hemorrhage: a pilot study.
AB  - BACKGROUND: Cerebral vasospasm (CVS) and cerebral infarction due to vasospasm
      (CIV) are major complications after spontaneous subarachnoid hemorrhage (SAH).
      Alteration of vasomotor tone has been postulated as an important factor in the
      pathogenesis of CVS. Members of the transforming growth factor-beta (TGF-beta)
      family and their receptors have been implicated in the regulation of vascular
      tone. METHODS: Serum levels of soluble endoglin (sEng) and plasma levels of TGF
      beta(1) of 20 consecutive SAH patients were analyzed within 15 days after SAH
      using ELISA and correlated with CVS, CIV and outcome. Twenty voluntary age- and
      sex-matched blood donors served as healthy controls (HCs). RESULTS: SAH patients
      showed significantly lower sEng serum levels and higher TGF-beta(1) plasma levels
      compared to HCs. Patients who developed Doppler sonographic CVS (dCVS) had
      significantly higher TGF-beta(1) levels. Patients with CIV and patients with
      hydrocephalus showed significantly lower sEng levels. On day 3, pSAH sEng levels
      below 3.88 ng/ml or TGF-beta(1) levels higher than 7.2 ng/ml had a predictive
      value for the development of CIV. Low mean sEng levels over the study period were
      highly predictive of poor long-term functional outcome (modified Rankin Scale
      >=2) at 6 months after SAH. CONCLUSIONS: Concentrations of the vasoactive factors
      sEng in serum and TGF-beta(1) in plasma are significantly altered in SAH patients
      compared to HCs. The results of this pilot study indicate that sEng could
      represent a novel prognostic biomarker for the onset of secondary complications
      and long-term functional outcome after SAH.

PMID- 22133667
TI  - Intramural hematoma of the pulmonary artery and hemopneumomediastinum after
      endobronchial ultrasound-guided transbronchial needle aspiration.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a
      safe and effective technique for the sampling of mediastinal and hilar
      adenopathies. We describe the first reported case of pulmonary artery intramural
      hematoma after EBUS-TBNA puncture of this artery. The complication was visualized
      by ultrasound and resolved spontaneously.

PMID- 22133668
TI  - Huntington's disease: current epidemiology and pharmacological management in UK
      primary care.
AB  - BACKGROUND: Recent debate suggests Huntington's disease (HD) may be more
      prevalent than previously reported. In addition, relatively little is known about
      current disease management. This study aims to provide epidemiological data and
      describe the pharmacological management of HD in the United Kingdom. METHODS: A
      primary care research database was accessed to identify incident and prevalent HD
      cases between January 1, 2004, and December 31, 2008. Patients with Read codes
      denoting a definite diagnosis or possible diagnosis, and undiagnosed patients
      with a positive family history were identified. A subset of patients with a
      definite diagnosis and prescribed medication indicating symptom onset was also
      identified. Epidemiological data were estimated. Pharmacological prescriptions to
      HD patients from 2004 to 2008 were identified, and prescription frequencies were
      grouped according to the British National Formulary categories. RESULTS: HD
      incidence estimates ranged from 0.44 to 0.78 per 100,000 person-years, and HD
      prevalence ranged from 5.96 to 6.54 per 100,000 of the population. Forty-four
      percent of pharmacological prescriptions targeted the central nervous system.
      Nearly half of the HD patients were prescribed antidepressants, and over 40% were
      prescribed analgesics. CONCLUSIONS: Although prevalence estimates fell short of
      figures suggested in recent debate, it is feasible that the true prevalence may
      be much higher than previously reported. Pharmacological management appears to
      rely heavily on central nervous system drugs and nutrition support. Many of these
      drugs are prescribed to HD patients for reasons other than the medication's
      primary use. Further work is required to evaluate the impact of alternative
      management strategies, such as therapist intervention, counselling, and
      organisation support, on the patients' quality of life.

PMID- 22133669
TI  - Frequent methamphetamine injection predicts emergency department utilization
      among street-involved youth.
AB  - OBJECTIVES: Methamphetamine (MA) use has been associated with health problems
      that commonly present in the emergency department (ED). This study sought to
      determine whether frequent MA injection was a risk factor for ED utilization
      among street-involved youth. STUDY DESIGN: Prospective cohort study. METHODS:
      Data were derived from a street-involved youth cohort known as the 'At Risk Youth
      Study'. Behavioural data including MA use were linked to ED records at a major
      inner-city hospital. Kaplan-Meier and Cox proportional hazards methods were used
      to determine the risk factors for ED utilization. RESULTS: Between September 2005
      and January 2007, 427 eligible participants were enrolled, among whom the median
      age was 21 (interquartile range 19-23) years and 154 (36.1%) were female. Within
      1 year, 163 (38.2%) visited the ED, resulting in an incidence density of 53.7 per
      100 person-years. ED utilization was significantly higher among frequent (i.e.
      >=daily) MA injectors (log-rank P = 0.004). In multivariate analysis, frequent MA
      injection was associated with an increased hazard of ED utilization (adjusted
      hazard ratio = 1.84, 95% confidence interval 1.04-3.25; P = 0.036). CONCLUSIONS:
      Street-involved youth who frequently inject MA appear to be at increased risk of
      ED utilization. The integration of MA-specific addiction treatment services
      within emergency care settings for high-risk youth is recommended.

PMID- 22133670
TI  - Incidence of hypertension and its risk factors in rural Kerala, India: a
      community-based cohort study.
AB  - OBJECTIVES: To investigate the incidence of hypertension and its risk factors in
      Kerala, India where the epidemiological transition is more advanced than
      elsewhere in India. STUDY DESIGN: Prospective cohort study. METHODS: A sample of
      297 individuals (aged 15-64 years) in rural Kerala, India, who were free of
      hypertension at study enrolment, were followed-up from 2003 to 2010. At
      enrolment, demographic characteristics and behavioural risk factors were
      determined by interview, and the participants underwent physical (blood pressure,
      height, weight and waist circumference) and biochemical examinations (fasting
      plasma glucose and serum lipids). At follow-up, blood pressure readings were
      repeated using the original tool following the same protocol. RESULTS: Nearly one
      quarter (23.6%) of the sample developed hypertension over a mean follow-up period
      of 7.1 (standard deviation 0.2) years. Age >=35 years [relative risk (RR) 4.00,
      95% confidence interval (CI) 2.37-6.03], current smoking [RR 1.99, 95% CI 1.14
      2.97, population-attributable risk percent (PAR%) 13.3%], high-normal blood
      pressure (RR 3.53 vs optimal blood pressure, 95% CI 2.17-5.28, PAR% 44.0%) and
      central obesity (RR 2.45, 95% CI 1.45-3.70, PAR% 40.4%) were significantly
      associated with incident hypertension. Collectively, current smoking, high-normal
      blood pressure and central obesity accounted for 70.1% of all new cases of
      hypertension. Awareness, treatment and control rates of incident hypertension
      were 42.9%, 22.9% and 11.4%, respectively. CONCLUSIONS: This rural sample showed
      a high incidence of hypertension. This underscores the need for primary
      prevention of hypertension through lifestyle modification strategies targeting
      individuals with high-normal blood pressure, central obesity and current smoking.
      The healthcare system needs to improve the level of awareness, treatment and
      control of hypertension in this population.

PMID- 22133671
TI  - NaHS relaxes rat cerebral artery in vitro via inhibition of l-type voltage
      sensitive Ca2+ channel.
AB  - H(2)S, a gaseous signalling molecule, relaxes blood vessels partly through
      activation of ATP-sensitive K(+) channels. It is however unclear whether H(2)S or
      its donors could affect other ion transporting proteins. The present study
      examined the hypothesis that NaHS, a H(2)S donor inhibits voltage-sensitive
      Ca(2+) channels and thus relaxes vascular smooth muscle cells (VSMC) in the
      cerebral arteries. NaHS dilated cerebral arteries from Sprague-Dawley rats with
      the same potency against pre-contraction by 5-HT and 60 mmol/L KCl, which were
      unaffected by several K(+) channel blockers, N(G)-nitro-l-arginine methyl ester
      or indomethacin, as assessed in wire myograph under an isometric condition.
      Likewise, NaHS also dilated cerebral arteries against myogenic constriction in
      pressurized myograph under an isobaric condition. NaHS concentration-dependently
      inhibited CaCl(2)-induced contraction in Ca(2+)-free, 60mM K(+)-containing Krebs
      solution. Patch clamp recordings showed that NaHS reduced the amplitude of l-type
      Ca(2+) currents in single myocytes isolated enzymatically from the cerebral
      artery. Calcium fluorescent imaging using fluo-4 showed a reduced [Ca(2+)](i) in
      60 mmol/L KCl-stimulated rat cerebral arteries in response to NaHS. H(2)S
      precursor l-cysteine-induced relaxation in cerebral arteries was inhibited by
      cystathionine gamma-lyase (CSE) inhibitor dl-propargylglycine. CSE was expressed
      in cerebral arteries. In summary, NaHS dilates rat cerebral arteries by reducing
      l-type Ca(2+) currents and suppressing [Ca(2+)](i) of arterial myocyte,
      indicating that NaHS relaxes cerebral arteries primarily through inhibiting
      Ca(2+) influx via Ca(2+) channels.

PMID- 22133672
TI  - Inhibiting TRPA1 ion channel reduces loss of cutaneous nerve fiber function in
      diabetic animals: sustained activation of the TRPA1 channel contributes to the
      pathogenesis of peripheral diabetic neuropathy.
AB  - Peripheral diabetic neuropathy (PDN) is a devastating complication of diabetes
      mellitus (DM). Here we test the hypothesis that the transient receptor potential
      ankyrin 1 (TRPA1) ion channel on primary afferent nerve fibers is involved in the
      pathogenesis of PDN, due to sustained activation by reactive compounds generated
      in DM. DM was induced by streptozotocin in rats that were treated daily for 28
      days with a TRPA1 channel antagonist (Chembridge-5861528) or vehicle. Laser
      Doppler flow method was used for assessing axon reflex induced by intraplantar
      injection of a TRPA1 channel agonist (cinnamaldehyde) and immunohistochemistry to
      assess substance P-like innervation of the skin. In vitro calcium imaging and
      patch clamp were used to assess whether endogenous TRPA1 agonists (4
      hydroxynonenal and methylglyoxal) generated in DM induce sustained activation of
      the TRPA1 channel. Axon reflex induced by a TRPA1 channel agonist in the plantar
      skin was suppressed and the number of substance P-like immunoreactive nerve
      fibers was decreased 4 weeks after induction of DM. Prolonged treatment with
      Chembridge-5861528 reduced the DM-induced attenuation of the cutaneous axon
      reflex and loss of substance P-like immunoreactive nerve fibers. Moreover, in
      vitro calcium imaging and patch clamp results indicated that reactive compounds
      generated in DM (4-hydroxynonenal and methylglyoxal) produced sustained
      activations of the TRPA1 channel, a prerequisite for adverse long-term effects.
      The results indicate that the TRPA1 channel exerts an important role in the
      pathogenesis of PDN. Blocking the TRPA1 channel provides a selective disease
      modifying treatment of PDN.

PMID- 22133673
TI  - Covalent magnetism, exchange interactions and anisotropy of the high temperature
      layered antiferromagnet MnB2.
AB  - The investigation of the electronic structure and magnetism for the compound
      MnB(2) with crystal structure type AlB(2) has been revisited to resolve
      contradictions between various experimental and theoretical results present in
      the literature. We find that MnB(2) exhibits an interesting example of a Kubler's
      covalent magnetism (Williams et al 1981 J. Appl. Phys. 52 2069). The covalent
      magnetism also appears to be the source of some disagreement between the
      calculated values of the magnetic moments and those given by neutron diffraction
      experiments. We show that this shortcoming is due to the atomic sphere
      approximation applied in earlier calculations. The application of the disordered
      local moment approach and the calculation of the inter-atomic exchange
      interactions within the Liechtenstein formalism reveal strong local moment
      antiferromagnetism with a high Neel temperature predicted from Monte Carlo
      simulations. A fully relativistic band structure calculation and then the
      application of the torque method yields a strong in-plane anisotropy of the Mn
      magnetic moments. The agreement of these results with neutron diffraction studies
      rules out any possible weak itinerant electron magnetism scenarios as proposed
      earlier for MnB(2).

PMID- 22133675
TI  - Full of beans? Early soy exposure associated with less feminine play in girls.

PMID- 22133676
TI  - Histone demethylase JMJD2B is required for tumor cell proliferation and survival
      and is overexpressed in gastric cancer.
AB  - Epigenetic alterations such as aberrant expression of histone-modifying enzymes
      have been implicated in tumorigenesis. Jumonji domain containing 2B (JMJD2B) is a
      newly identified histone demethylase that regulates chromatin structure or gene
      expression by removing methyl residues from trimethylated lysine 9 on histone H3.
      Recent observations have shown oncogenic activity of JMJD2B. We explored the
      functional role of JMJD2B in cancer cell proliferation, survival and
      tumorigenesis, and determined its expression profile in gastric cancer. Knocking
      down JMJD2B expression by small interfering RNA (siRNA) in gastric and other
      cancer cells inhibited cell proliferation and/or induced apoptosis and elevated
      the expression of p53 and p21(CIP1) proteins. The enhanced p53 expression
      resulted from activation of the DNA damage response pathway. JMJD2B knockdown
      markedly suppressed xenograft tumor growth in vivo in mice. Moreover, JMJD2B
      expression was increased in primary gastric-cancer tissues of humans. Thus,
      JMJD2B is required for sustained proliferation and survival of tumor cells in
      vitro and in vivo, and its aberrant expression may contribute to the pathogenesis
      of gastric cancer.

PMID- 22133677
TI  - The human Ino80 binds to microtubule via the E-hook of tubulin: implications for
      the role in spindle assembly.
AB  - The human INO80 chromatin remodeling complex, comprising the Ino80 ATPase
      (hIno80) and the associated proteins such as Tip49a, has been implicated in a
      variety of nuclear processes other than transcription. We previously have found
      that hIno80 interacts with tubulin and co-localizes with the mitotic spindle and
      is required for spindle formation. To better understand the role of hIno80 in
      spindle formation, we further investigated the interaction between hIno80 and
      microtubule. Here, we show that the N-terminal domain, dispensable for the
      nucleosome remodeling activity, is important for hIno80 to interact with tubulin
      and co-localize with the spindle. The hIno80 N-terminal domain binds to monomeric
      tubulin and polymerized microtubule in vitro, and the E-hook of tubulin, involved
      in the polymerization of microtubule, is critical for this binding. Tip49a, which
      has been reported to associate with the spindle, does not bind to microtubule in
      vitro and dispensable for spindle formation in vivo. These results suggest that
      hIno80 can play a direct role in the spindle assembly independent of its
      chromatin remodeling activity.

PMID- 22133678
TI  - Epitope mapping of antibodies against TDP-43 and detection of protease-resistant
      fragments of pathological TDP-43 in amyotrophic lateral sclerosis and
      frontotemporal lobar degeneration.
AB  - TAR DNA-binding protein of 43 kDa (TDP-43) is the major component of the
      intracellular inclusions in amyotrophic lateral sclerosis (ALS) and
      frontotemporal lobar degeneration (FTLD). Here, we show that both monoclonal
      (60019-2-Ig) and polyclonal (10782-2-AP) anti-TDP-43 antibodies recognize amino
      acids 203-209 of human TDP-43. The monoclonal antibody labeled human TDP-43 by
      recognizing Glu204, Asp205 and Arg208, but failed to react with mouse TDP-43. The
      antibodies stained the abnormally phosphorylated C-terminal fragments of 24-26
      kDa in addition to normal TDP-43 in ALS and FTLD brains. Immunoblot analysis
      after protease treatment demonstrated that the epitope of the antibodies
      (residues 203-209) constitutes part of the protease-resistant domain of TDP-43
      aggregates which determine a common characteristic of the pathological TDP-43 in
      both ALS and FTLD-TDP. The antibodies and methods used in this study will be
      useful for the characterization of abnormal TDP-43 in human materials, as well as
      in vitro and animal models for TDP-43 proteinopathies.

PMID- 22133674
TI  - Toward understanding Machado-Joseph disease.
AB  - Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3),
      is the most common inherited spinocerebellar ataxia and one of many polyglutamine
      neurodegenerative diseases. In MJD, a CAG repeat expansion encodes an abnormally
      long polyglutamine (polyQ) tract in the disease protein, ATXN3. Here we review
      MJD, focusing primarily on the function and dysfunction of ATXN3 and on advances
      toward potential therapies. ATXN3 is a deubiquitinating enzyme (DUB) whose highly
      specialized properties suggest that it participates in ubiquitin-dependent
      proteostasis. By virtue of its interactions with VCP, various ubiquitin ligases
      and other ubiquitin-linked proteins, ATXN3 may help regulate the stability or
      activity of many proteins in diverse cellular pathways implicated in proteotoxic
      stress response, aging, and cell differentiation. Expansion of the polyQ tract in
      ATXN3 is thought to promote an altered conformation in the protein, leading to
      changes in interactions with native partners and to the formation of insoluble
      aggregates. The development of a wide range of cellular and animal models of MJD
      has been crucial to the emerging understanding of ATXN3 dysfunction upon polyQ
      expansion. Despite many advances, however, the principal molecular mechanisms by
      which mutant ATXN3 elicits neurotoxicity remain elusive. In a chronic
      degenerative disease like MJD, it is conceivable that mutant ATXN3 triggers
      multiple, interconnected pathogenic cascades that precipitate cellular
      dysfunction and eventual cell death. A better understanding of these complex
      molecular mechanisms will be important as scientists and clinicians begin to
      focus on developing effective therapies for this incurable, fatal disorder.

PMID- 22133679
TI  - Negative-feedback regulation of ATP release: ATP release from cardiomyocytes is
      strictly regulated during ischemia.
AB  - Extracellular ATP acts as a potent agonist on cardiomyocytes, inducing a broad
      range of physiological responses via P2 purinoceptors. Its concentration in the
      interstitial space within the heart is elevated during ischemia or hypoxia due to
      its release from a number of cell types, including cardiomyocytes. However, the
      exact mechanism responsible for the release of ATP from cardiomyocytes during
      ischemia is not known. In this study, we investigated whether and how the release
      of ATP was strictly regulated during ischemia in cultured neonatal rat
      cardiomyocytes. Ischemia was mimicked by oxygen-glucose deprivation (OGD).
      Exposure of cardiomyocytes to OGD resulted in an increase in the concentration of
      extracellular ATP shortly after the onset of OGD (15 min), and the increase was
      reversed by treatment with blockers of maxi-anion channels. Unexpectedly, at 1
      and 2h after the onset of OGD, the blocking of maxi-anion channels increased the
      concentration of extracellular ATP, and the increase was significantly suppressed
      by co-treatment with blockers of hemichannels, suggesting that ATP release via
      maxi-anion channels was involved in the suppression of ATP release via
      hemichannels during persistent OGD. Here we show the possibility that the release
      of ATP from cardiomyocytes was strictly regulated during ischemia by negative
      feedback mechanisms; that is, maxi-anion channel-derived ATP-induced suppression
      of ATP release via hemichannels in cardiomyocytes.

PMID- 22133680
TI  - Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial
      carcinoma.
AB  - BACKGROUND: We investigated the role of the programmed cell death 4 (PDCD4) tumor
      suppressor gene in specimens of transitional cell carcinoma and of healthy
      individuals. METHODS: PDCD4 immunohistochemical expression was investigated in
      294 cases in histologically proven transitional cell carcinoma in different
      tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma,
      stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25
      metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with
      real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression.
      RESULTS: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly
      with histopathological progression of the tumor (p<0001). Controls showed strong
      nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in
      tissue corresponded to PDCD4 suppression. CONCLUSIONS: These data support a
      decisive role for PDCD4 down regulation in transitional cell carcinoma and
      confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4
      immunohistochemical staining turns out to be a possible diagnostic marker for
      transitional cell carcinoma.

PMID- 22133681
TI  - Small RNA transcriptome investigation based on next-generation sequencing
      technology.
AB  - Over the past decade, there has been a growing realization that studying the
      small RNA transcriptome is essential for understanding the complexity of
      transcriptional regulation. With an increased throughput and a reduced cost, next
      generation sequencing technology has provided an unprecedented opportunity to
      measure the extent and complexity of small RNA transcriptome. Meanwhile, the
      large amount of obtained data and varied technology platforms have also posed
      multiple challenges for effective data analysis and mining. To provide some
      insight into the small RNA transcriptome investigation, this review describes the
      major small RNA classes, experimental methods to identify small RNAs, and
      available bioinformatics tools and databases.

PMID- 22133682
TI  - Nogo receptor 3, a paralog of Nogo-66 receptor 1 (NgR1), may function as a NgR1
      co-receptor for Nogo-66.
AB  - Nogo-A is a major myelin associated inhibitor that blocks regeneration of injured
      axons in the central nervous system (CNS). Nogo-66 (a 66-residue domain of Nogo
      A) expressed on the surface of oligodendrocytes has been shown to directly
      interact with Nogo-66 receptor 1 (NgR1). A number of additional components of
      NgR1 receptor complex essential for its signaling have been uncovered. However,
      detailed composition of the complex and its signaling mechanisms remain to be
      fully elucidated. In this study, we show that Nogo receptor 3 (NgR3), a paralog
      of NgR1, is a binding protein for NgR1. The interaction is highly specific
      because other members of the reticulin family, to which Nogo-A belongs, do not
      bind to NgR3. Neither does NgR3 show any binding activity with Nogo receptor 2
      (NgR2), another NgR1 paralog. Majority of NgR3 domains are required for its
      binding to NgR1. Moreover, a truncated NgR3 with the membrane anchoring domain
      deleted can function as a decoy receptor to reverse neurite outgrowth inhibition
      caused by Nogo-66 in culture. These in vitro results, together with previously
      reported overlapping expression profile between NgR1 and NgR3, suggest that NgR3
      may be associated with NgR1 in vivo and that their binding interface may be
      targeted for treating neuronal injuries.

PMID- 22133683
TI  - Identification of compatibility between ooplasmic factor and sperm gene in the
      intersubspecific crosses involving DDK and PWK mice strains.
AB  - The DDK strain (Mus musculus domesticus) of inbred mouse has a unique peculiarity
      known as DDK syndrome. The DDK females are mostly infertile when crossed with
      males of other inbred strains, while DDK males exhibit normal fertility in the
      reciprocal crosses, as intrastrain matings. This DDK syndrome has been
      demonstrated to be caused by an incompatibility system between DDK ooplasmic
      factor and the sperm gene of other strains owing to the ovum mutant (Om) locus on
      mouse Chromosome 11. Recently, it was reported that DDK females are fully fertile
      when crossed to males of MOM (M. m. molossinus) and CASP (M. m. castaneus)
      strains, indicating that no incompatibilities exist between DDK ooplasmic factor
      and sperm gene of MOM or CASP males. In the present study, DDK females were found
      to be also fully fertile when crossed to the males of PWK wild-derived inbred
      strain (originated from Czech Republic wild mice, M. m. musculus). The crosses of
      DDK females*F(1) (DDK?*PWK?) males also resulted in normal fertility.
      Furthermore, the transmission ratios of Om alleles from these F(1) males to their
      backcross N(2) offspring are 50%:50% as genotyped by microsatellite markers
      closely linked to Om locus. Moreover, it was demonstrated that PWK females are
      also fully fertile when crossed to DDK males. All above results indicated that no
      incompatibility exists between ooplasmic factor and sperm gene in the
      intersubspecific crosses with DDK and PWK strains. PWK strain would also be
      useful for further investigations on the DDK syndrome, and DDK strain can be used
      more widely for various studies in the mouse.

PMID- 22133684
TI  - Avian influenza A virus H5N1 causes autophagy-mediated cell death through
      suppression of mTOR signaling.
AB  - Of the few avian influenza viruses that have crossed the species barrier to
      infect humans, the highly pathogenic influenza A (H5N1) strain has claimed the
      lives of more than half of the infected patients. With largely unknown mechanism
      of lung injury by H5N1 infection, acute respiratory distress syndrome (ARDS) is
      the major cause of death among the victims. Here we present the fact that H5N1
      caused autophagic cell death through suppression of mTOR signaling. Inhibition of
      autophagy, either by depletion of autophagy gene Beclin1 or by autophagy
      inhibitor 3-methyladenine (3-MA), significantly reduced H5N1 mediated cell death.
      We suggest that autophagic cell death may contribute to the development of ARDS
      in H5N1 influenza patients and inhibition of autophagy could therefore become a
      novel strategy for the treatment of H5N1 infection.

PMID- 22133685
TI  - TSA1 interacts with CSN1/CSN and may be functionally involved in Arabidopsis
      seedling development in darkness.
AB  - The COP9 signalosome (CSN) is a multiprotein complex which participates in
      diverse cellular and developmental processes. CSN1, one of the subunits of CSN,
      is essential for assembly of the multiprotein complex via PCI (proteasome, COP9
      signalosome and initiation factor 3) domain in the C-terminal half of CSN1.
      However, the role of the N-terminal domain (NTD) of CSN1, which is critical for
      the function of CSN, is not completely understood. Using a yeast two-hybrid (Y2H)
      screen, we found that the NTD of CSN1 interacts with TSK-associating protein 1
      (TSA1), a reported Ca(2+)-binding protein. The interaction between CSN1 and TSA1
      was confirmed by co-immunoprecipitation in Arabidopsis. tsa1 mutants exhibited a
      short hypocotyl phenotype in darkness but were similar to wild-type Arabidopsis
      under white light, which suggested that TSA1 might regulate Arabidopsis hypocotyl
      development in the dark. Furthermore, the expression of TSA1 was significantly
      lower in a csn1 null mutant (fus6), while CSN1 expression did not change in a
      tsa1 mutant with weak TSA1 expression. Together, these findings suggest a
      functional relationship between TSA1 and CSN1 in seedling development.

PMID- 22133686
TI  - Development of upland rice introgression lines and identification of QTLs for
      basal root thickness under different water regimes.
AB  - Introgression lines (ILs) are valuable materials for identifying quantitative
      trait loci (QTLs), evaluating genetic interactions, and marker assisted breeding.
      A set of 430 ILs (BC(5)F(3)) containing segments from upland tropical japonica
      cultivar IRAT109 in a lowland temperate japonica cultivar Yuefu background were
      developed. One hundred and seventy-six polymorphic markers were used to identify
      introgressed segments. No segment from IRAT109 was found in 160 lines.
      Introgressed segments of the other 270 lines covered 99.1% of the donor genome.
      The mean number of introgressed donor segments per individual was 3.3 with an
      average length of 14.4 cM. QTL analysis was conducted on basal root thickness
      (BRT) of the 270 ILs grown under irrigated lowland, upland and hydroponic
      conditions. A total of 22 QTLs affecting BRT were identified, six QTLs (qBRT3.1,
      qBRT3.2, qBRT6.1, qBRT8.2, qBRT9.1, and qBRT9.2) were consistently expressed
      under at least two environments (location and water regime), and qBRT7.2 was a
      new BRT QTL identified under lowland conditions. IL255 containing qBRT9.1 showed
      an increase of 10.09% and 7.07% BRT over cultivar Yuefu when grown under upland
      and lowland conditions, respectively. Using a population of 304 F(2:3) lines
      derived from the cross IL255*Yuefu, qBRT9.1 was validated and mapped to a 1.2 cM
      interval between RM24271 and RM566. The presence of qBRT9.1 explained 12% of BRT
      variation. The results provide upland rice ILs and BRT QTLs for analyzing the
      genetic basis of drought resistance, detecting favorable genes from upland rice,
      and rice drought resistance breeding.

PMID- 22133687
TI  - A cotton mitogen-activated protein kinase (GhMPK6) is involved in ABA-induced
      CAT1 expression and H(2)O(2) production.
AB  - The mitogen-activated protein kinase (MAPK) cascade is one of the major and
      evolutionally conserved signaling pathways and plays a pivotal role in the
      regulation of stress and developmental signals in plants. Here, we identified one
      gene, GhMPK6, encoding an MAPK protein in cotton. GFP fluorescence assay
      demonstrated that GhMAPK6 is a cytoplasm localized protein. Quantitative RT-PCR
      analysis revealed that mRNA accumulation of GhMPK6 was significantly promoted by
      abscisic acid (ABA). Overexpression of GhMPK6 gene in the T-DNA insertion mutant
      atmkk1 (SALK_015914) conferred a wild-type phenotype to the transgenic plants in
      response to ABA. Under ABA treatment, cotyledon greening/expansion in GhMPK6
      transgenic lines and wild type was significantly inhibited, whereas the atmkk1
      mutant showed a relatively high cotyledon greening/expansion ratio. Furthermore,
      CAT1 expression and H(2)O(2) levels in leaves of GhMPK6 transgenic lines and wild
      type were remarkably higher than those of atmkk1 mutant with ABA treatment.
      Collectively, our results suggested that GhMPK6 may play an important role in ABA
      induced CAT1 expression and H(2)O(2) production.

PMID- 22133688
TI  - A critical care nurse practitioner's prescribing using standing orders and
      authorised prescribing when performing a critical care outreach role: a clinical
      audit.
AB  - OBJECTIVE: This paper assesses the frequency of prescribing and the types of
      medications prescribed by a New Zealand critical care nurse practitioner (NP)
      whilst performing a critical care outreach role. METHOD: A before and after audit
      was conducted from June 2006 to July 2008. Audit data were collected
      prospectively and analysed retrospectively. Data collected between July 2006 and
      June 2007 when standing orders were used were compared to data collected between
      July 2007 and June 2008 when the NP was authorised to prescribe. Data were
      analysed using count, chi-square, the Fisher's Exact Test and Phi. FINDINGS: The
      NP completed 1061 patient visits. When compared to using standing orders, the NP
      prescribed a greater number and a wider range of medications when authorised to
      prescribe (chi2=9.280, p=.002, Phi=.094). Electrolytes and analgesics were the
      most common medications prescribed in both audit periods. CONCLUSION: The results
      provide insight into critical care NP prescribing practice to better inform
      future critical care workforce development.

PMID- 22133689
TI  - Comprehensive hemodynamic assessment of 305 normal CarboMedics mitral valve
      prostheses based on early postimplantation echocardiographic studies.
AB  - BACKGROUND: Two-dimensional (2D) and Doppler-derived echocardiographic data on
      normal CarboMedics (CM) mechanical mitral valve prosthesis function have been
      reported but are limited. METHODS: Comprehensive retrospective 2D and Doppler
      echocardiographic assessment of 305 normal CM mechanical mitral valve prostheses
      (272 Standard and 33 Optiform) was performed early after implantation. The early
      postimplantation hemodynamic profiles of 80 patients were compared with profiles
      obtained by follow-up transthoracic echocardiography performed <1 year after
      implantation. RESULTS: CM Standard and Optiform prostheses had similar
      hemodynamic profiles. With mean +/- 2 SDs used to define the normal distribution
      of values for hemodynamic variables, the calculated normal range of values was as
      follows: mean gradient, 2 to 7 mm Hg; peak early mitral diastolic velocity, 1.3
      to 2.4 m/sec; time-velocity integral (TVI) of the mitral valve prosthesis
      (TVI(MVP)), 20 to 50 cm; ratio of TVI(MVP) to the TVI of the left ventricular
      outflow tract, 0.9 to 2.5; pressure half-time, 35 to 99 msec; and effective
      orifice area, 1.17 to 3.25 cm(2). Patients with severe prosthesis-patient
      mismatch (indexed effective orifice area <= 0.9 cm(2)/m(2)) had significantly
      higher mean gradients, peak early mitral diastolic velocities, TVI(MVP), ratios
      of TVI(MVP) to the TVI of the left ventricular outflow tract, and pressure half
      time values than values without severe prosthesis-patient mismatch, but none had
      pressure half-time values > 120 msec. Among the 80 patients with follow-up
      transthoracic echocardiography within 1 year after implantation, no significant
      differences were noted between early postimplantation findings and follow-up
      hemodynamic profiles. CONCLUSIONS: This study establishes parameters (mean +/- 2
      SD) defining the distribution of findings for Doppler-derived hemodynamic data
      with normal CM mechanical mitral valve prostheses. Prostheses with hemodynamic
      values outside these parameters are likely dysfunctional; however, prosthesis
      dysfunction may be present even when hemodynamic values are within these ranges.

PMID- 22133690
TI  - Identification of distinct populations of prostasomes that differentially express
      prostate stem cell antigen, annexin A1, and GLIPR2 in humans.
AB  - In addition to sperm cells, seminal fluid contains various small membranous
      vesicles. These include prostasomes, membrane vesicles secreted by prostate
      epithelial cells. Prostasomes have been proposed to perform a variety of
      functions, including modulation of (immune) cell activity within the female
      reproductive tract and stimulation of sperm motility and capacitation. How
      prostasomes mediate such diverse functions, however, remains unclear. In many
      studies, vesicles from the seminal plasma have been categorized collectively as a
      single population of prostasomes; in fact, they more likely represent a
      heterogeneous mixture of vesicles produced by different reproductive glands and
      secretory mechanisms. We here characterized membranous vesicles from seminal
      fluid obtained from vasectomized men, thereby excluding material from the testes
      or epididymides. Two distinct populations of vesicles with characteristic sizes
      (56 +/- 13 nm vs. 105 +/- 25 nm) but similar equilibrium buoyant density (~1.15
      g/ml) could be separated by using the distinct rates with which they floated into
      sucrose gradients. Both types of vesicle resembled exosomes in terms of their
      buoyant density, size, and the presence of the ubiquitous exosome marker CD9. The
      protein GLIPR2 was found to be specifically enriched in the lumen of the smaller
      vesicles, while annexin A1 was uniquely associated with the surface of the larger
      vesicles. Prostate stem-cell antigen (PSCA), a prostate-specific protein, was
      present on both populations, thereby confirming their origin. PSCA was, however,
      absent from membrane vesicles in the seminal fluid of some donors, indicating
      heterogeneity of prostasome characteristics between individuals.

PMID- 22133691
TI  - A decrease in DKK1, a WNT inhibitor, contributes to placental lipid accumulation
      in an obesity-prone rat model.
AB  - Placenta, as the sole transport mechanism between mother and fetus, links the
      maternal physical state and the immediate as well as lifelong outcomes of the
      offspring. The present study examined the consequences of maternal obesity on
      placental lipid accumulation and metabolism. Pregnant obesity-prone (OP) and
      obesity-resistant (OR) rat strains were fed a control diet throughout gestation.
      Placentas were collected on Gestational Day 21 for mRNA and oxidative stress
      analysis, and frozen placental sections were analyzed for fat accumulation as
      well as beta-catenin and Dickkopf homolog 1 (Xenopus laevis) (DKK1) localization.
      JEG3 trophoblast cells were cultured in vitro to determine the relationship
      between DKK1 and lipid accumulation. Maternal plasma and placental nonesterified
      fatty acids and triglycerides (TG) were elevated in OP dams. Placental Dkk1 mRNA
      content was 4-fold lower in OP placentas, and a significant increase was noted in
      beta-catenin accumulation as well as in mRNA content of fat transport and TG
      synthesis genes, including Ppard (peroxisome proliferator-activated receptor
      delta), Slc27a1 (fatty acid transport protein 1; also known as Fatp1), Cd36
      (cluster of differentiation 36; also known as fatty acid translocation [Fat]),
      Lipin1, and Lipin3. Significant lipid accumulation was found within the decidual
      zones in OP, but not OR, placentas, and thickness of the decidual and junctional
      zones was significantly smaller in OP than in OR placentas. Overexpression of
      DKK1 in JEG3 cells decreased lipid accumulation and mRNA content of PPARD,
      SLC27A1, CD36, LIPIN1, and LIPIN3. Our results demonstrate that DKK1 is
      regulating certain aspects of placental lipid metabolism through the WNT
      signaling pathway.

PMID- 22133692
TI  - Brief exposure to progesterone during a critical neonatal window prevents uterine
      gland formation in mice.
AB  - Uterine gland development (adenogenesis) in mice begins on Postnatal Day (PND) 5
      and is completed in adulthood. Adenogenesis depends on estrogen receptor 1, and
      progesterone (P4) inhibits mitogenic effects of estrogen on uterine epithelium.
      This progestin-induced effect has been used to inhibit uterine gland development;
      progestin treatment of ewes for 8 wk from birth has produced infertile adults
      lacking uterine glands. The goals of the present study were to determine if a
      window of susceptibility to P4-mediated inhibition of uterine gland development
      exists in mice and whether early P4 treatment abolishes adenogenesis and
      fertility. Mice were injected daily with P4 (40 MUg/g) or vehicle during various
      postnatal windows. Adenogenesis, cell proliferation, and expression of key
      morphoregulatory transcripts and proteins were examined in uteri at PNDs 10 and
      20. Additionally, adenogenesis was assessed in isolated uterine epithelium.
      Treatment during PNDs 3-9, 5-9, or 3-7 abolished adenogenesis at PND 10, whereas
      treatments during PNDs 3-5 and 7-9 did not. Critically, mice treated during PNDs
      3-9 lacked glands in adulthood, indicating that adenogenesis did not resume after
      this treatment. However, glands were present by PND 20 and later following
      treatment during PNDs 5-9 or 3-7, whereas treatment during PNDs 10-16 produced
      partial inhibition of adenogenesis at PND 20 and later. Epithelial proliferation
      at PND 10 was low following P4 treatment (PNDs 3-9) but exceeded that in controls
      at PND 20, indicating a rebound of epithelial proliferation following treatment.
      Messenger RNA for Wnt, Fzd, and Hox genes was altered by neonatal P4 treatment.
      All groups cycled during adulthood. Mice treated with P4 during PNDs 3-9, but not
      during other developmental windows, showed minimal fertility in adulthood. In
      summary, brief P4 treatment (7 days) during a critical neonatal window (PNDs 3-9)
      transiently inhibited epithelial proliferation but totally and permanently
      blocked adenogenesis and adult fertility. This resulted in permanent loss of
      uterine glands and, essentially, total infertility during adulthood. The narrow
      window for inhibition of adenogenesis identified here may have implications for
      development of this methodology as a contraceptive strategy for animals.

PMID- 22133693
TI  - An accidental andrologist.

PMID- 22133694
TI  - Timing sexual differentiation: full functional sex reversal achieved through
      silencing of a single insulin-like gene in the prawn, Macrobrachium rosenbergii.
AB  - In Crustacea, an early evolutionary group (~50 000 species) inhabiting most
      ecological niches, sex differentiation is regulated by a male-specific androgenic
      gland (AG). The identification of AG-specific insulin-like factors (IAGs) and
      genomic sex markers offers an opportunity for a deeper understanding of the
      sexual differentiation mechanism in crustaceans and other arthropods. Here, we
      report, to our knowledge, the first full and functional sex reversal of male
      freshwater prawns (Macrobrachium rosenbergii) through the silencing of a single
      IAG-encoding gene. These "neofemales" produced all-male progeny, as proven by sex
      specific genomic markers. This finding offers an insight regarding the biology
      and evolution of sex differentiation regulation, with a novel perspective for the
      evolution of insulin-like peptides. Our results demonstrate how temporal
      intervention with a key regulating gene induces a determinative, extreme
      phenotypic shift. Our results also carry tremendous ecological and commercial
      implications. Invasive and pest crustacean species represent genuine concerns
      worldwide without an apparent solution. Such efforts might, therefore, benefit
      from sexual manipulations, as has been successfully realized with other
      arthropods. Commercially, such manipulation would be significant in sexually
      dimorphic cultured species, allowing the use of nonbreeding, monosex populations
      while dramatically increasing yield and possibly minimizing the invasion of
      exotic cultured species into the environment.

PMID- 22133695
TI  - Seminiferous cord formation is regulated by hedgehog signaling in the marsupial.
AB  - The signaling molecule DHH, secreted by Sertoli cells, has essential regulatory
      functions in testicular differentiation. DHH is required for the differentiation
      of peritubular myoid cells that line the seminiferous cords and steroidogenic
      Leydig cells. The testicular cords in Dhh-null male mice lack a basal lamina and
      develop abnormally. To date, the DHH-signaling pathway has never been examined
      outside of any eutherian mammals. This study examined the effects of inhibition
      of DHH signaling in a marsupial mammal, the tammar wallaby, by culturing gonads
      in vitro in the presence of the hedgehog-signaling inhibitors cyclopamine and
      forskolin. Disruption of hedgehog signaling in the tammar testes caused highly
      disorganized cord formation. SOX9 protein remained strongly expressed in Sertoli
      cells, laminin distribution was highly fragmented, and germ cells were
      distributed around the cortical regions of treated testes in an ovarianlike
      morphology. This suggests that hedgehog signaling regulates cord formation in the
      tammar wallaby testis as it does in eutherian mammals. These data demonstrate
      that the hedgehog pathway has been highly conserved in mammals for at least 160
      million years.

PMID- 22133696
TI  - Maternal-restraint stress increases oocyte aneuploidy by impairing metaphase I
      spindle assembly and reducing spindle assembly checkpoint proteins in mice.
AB  - Studies in both humans and animals suggest detrimental effects of psychological
      stress on reproduction. Although our recent study shows that maternal-restraint
      stress diminishes oocyte developmental potential, the mechanism behind this
      effect is unknown. This prompted us to study the potential role of maternal
      restraint stress in the genesis of aneuploidy during meiosis I. At 24 h after
      equine chorionic gonadotropin injection, mice were subjected to restraint stress
      for 24 h. After the restraint, some mice were killed to recover immature oocytes
      for in vitro maturation, while others were injected with human chorionic
      gonadotropin to recover in vivo matured oocytes. Analysis on chromosome
      complements of both mature oocytes and parthenotes confirmed that maternal
      restraint increased aneuploidy in both in vivo and in vitro matured oocytes and
      that the percentage of aneuploid oocytes were three times higher in the earlier
      matured oocytes than in the later matured ones. Further observations indicated
      that maternal restraint 1) impaired metaphase I (MI) spindle assembly while
      inhibiting MAPK activities, 2) accelerated progression of anaphase I while down
      regulating the expression of spindle assembly checkpoint (SAC) proteins, and 3)
      induced intraoocyte oxidative stress. The following possible model was proposed
      to explain the results. Maternal-restraint stress increased oocyte aneuploidy by
      impairing MI spindle assembly and decreasing the SAC. Whereas abnormal spindles
      would affect centromere attachments, a reduction in SAC would accelerate the
      anaphase I progression. Failure of centromere attachment, together with the
      hastened anaphase, would result in nondisjunction of the unattached chromosomes.
      Furthermore, maternal-restraint stress might also impair spindle assembly and SAC
      function by inducing intraoocyte oxidative stress, which would then reduce MAPK
      activity, a critical regulator of microtubule assembly and the establishment and
      maintenance of the SAC during oocyte maturation.

PMID- 22133697
TI  - Ziprasidone for psychotic disorders: a meta-analysis and systematic review of the
      relationship between pharmacokinetics, pharmacodynamics, and clinical profile.
AB  - BACKGROUND: Among atypical antipsychotics, ziprasidone exhibits a unique clinical
      profile. However, prescription rates for this medication remain among the lowest
      of all atypical antipsychotics. OBJECTIVE: The present meta-analysis examined
      premature study discontinuation (PSD) and dose-response associated with
      ziprasidone. Furthermore, a systematic review of the clinical pharmacokinetic and
      pharmacodynamic properties and tolerability of ziprasidone was conducted to
      explain the meta-analytic findings. METHODS: A systematic search was performed in
      the electronic databases PubMed and EMBASE using the key words ziprasidone,
      randomized, positron emission tomography, pharmacokinetic, and tolerability. This
      search looked for open-label or blinded studies of oral ziprasidone use in
      patients with psychoses (schizophrenia-spectrum disorders and/or bipolar mania)
      published between January 1, 1992, and February 1, 2011. Comparisons with
      antipsychotics for which there were <3 studies in total were excluded. PSD (all
      causes) was used as a measure of overall effectiveness. RESULTS: Thirty-one
      studies were included in the final analysis. The rates of PSD were significantly
      higher with ziprasidone compared with olanzapine (inefficacy and all causes, P <
      0.001) and risperidone (all causes, P = 0.004). In contrast, the rates of PSD due
      to inefficacy and adverse events were significantly lower with ziprasidone
      compared with quetiapine (P = 0.03) and haloperidol (P = 0.03), respectively. On
      dose-response analysis, the rate of all-cause PSD was significantly lower with
      combined 120-160 mg/d compared with placebo (P = 0.001). Low levels of
      hyperprolactinemia and weight gain/metabolic adverse events, and moderate
      extrapyramidal symptoms and corrected QT-interval prolongation were reported with
      ziprasidone use. Ziprasidone exposure was increased when the medication was
      administered with food, irrespective of fat content. Ziprasidone 120-160 mg/d was
      correlated with 60% to 80% occupancy in studies of D(2) binding with the
      administration of multiple doses. However, the same occupancy was achieved with
      single-dose administration at much lower doses (20-60 mg/d). CONCLUSIONS: The
      findings from this meta-analysis and review suggest that ziprasidone 120-160 mg/d
      is a less effective treatment for psychotic disorders compared with olanzapine
      and risperidone, but that the low levels of hyperprolactinemia and weight
      gain/metabolic adverse events associated with ziprasidone may make it a useful
      option in patients in whom antipsychotics are poorly tolerated for these reasons.

PMID- 22133698
TI  - Safety of low-frequency transcranial ultrasound in permanent middle cerebral
      artery occlusion in spontaneously hypertensive rats.
AB  - BACKGROUND: Some studies suggest that low-frequency transcranial ultrasound
      (LFTUS) can enhance thrombolysis, but other studies suggest that it may have
      adverse effects on intracranial tissues. We previously reported that LFTUS with
      appropriate parameters was effective and safe in a normotensive rat model of
      thromboembolic middle cerebral artery occlusion (MCAO) stroke. The goal of this
      study was to test the safety of this strategy in a spontaneously hypertensive rat
      (SHR) model of permanent MCAO. METHODS: Right MCAO was achieved in male SHRs
      using intraluminal nylon sutures. Rats exhibiting left hemiparesis were randomly
      assigned to one of four different groups: (1) normal saline (NS) group (n = 8),
      intravenous administration of NS as placebo at 3 h after MCAO; (2) NS+LFTUS group
      (n = 10), NS administration with simultaneous application of LFTUS (480.4 kHz,
      continuous wave, at an intensity of 0.3 W/cm(2)) for 1 h; (3) tissue plasminogen
      activator (tPA) group (n = 11), intravenous administration of alteplase (10 mg/kg
      body weight) over 1 h instead of NS; or (4) tPA+LFTUS group (n = 11), tPA
      administration and application of LFTUS. Twenty-four hours after treatment,
      neurological change was evaluated, and brains were removed and examined
      histologically. RESULTS: There was no significant difference (p > 0.09) when
      comparing changes in neurologic status and body weight, infarct ratio, edema
      ratio, or hemorrhagic transformation among the four groups. CONCLUSIONS: Our
      findings suggest that sonothrombolytic treatment with LFTUS with appropriate
      parameters is safe when used for the treatment of ischemic stroke in hypertensive
      rats under the undesired permanent MCAO condition.

PMID- 22133699
TI  - Studies on the interaction between chromium(VI) and human serum albumin:
      spectroscopic approach.
AB  - The interaction between Cr(2)O(7)(2-) and human serum albumin (HSA) was
      investigated using fluorescence, UV/vis, FT-IR, CD spectroscopy, and molecular
      modeling method. The experimental results showed that the fluorescence quenching
      of HSA by Cr(2)O(7)(2-) is a result of the formation of HSA-chromium(VI) complex;
      static quenching was confirmed to result in the fluorescence quenching. The
      corresponding thermodynamic parameters showed that the process of binding
      Cr(2)O(7)(2-) on HSA was a spontaneous molecular interaction procedure. Ionic, H
      bonds and van der Waals interactions play a major role in stabilizing the
      complex. The Cr(2)O(7)(2-) altered the environments of Trp and Tyr residues in
      HSA.

PMID- 22133700
TI  - Spectrofluorimetric study of the interaction between europium(III) and
      moxifloxacin in micellar solution and its analytical application.
AB  - A sensitive spectrofluorimetric method has been developed for the determination
      of moxifloxacin (MOX) using europium(III)-MOX complex as a fluorescence probe in
      the presence of an anionic surfactant, sodium dodecyl benzene sulfonate (SDBS).
      The fluorescence (FL) intensity of Eu(3+) was enhanced by complexation with MOX
      at 614 nm after excitation at 373 nm. The FL intensity of the Eu(3+)-MOX complex
      was significantly intensified in the presence of SDBS. Under the optimum
      conditions, it was found that the enhanced FL intensity of the system showed a
      good linear relationship with the concentration of MOX over the range of 1.8 *
      10(-11)-7.3 * 10(-9) g mL(-1) with a correlation coefficient of 0.9998. The limit
      of detection of MOX was found to be 2.8 * 10(-12) g mL(-1) with relative standard
      deviation (RSD) of 1.25% for 5 replicate determination of 1.5 * 10(-8) g mL(-1)
      MOX. The proposed method is simple, offers higher sensitivity with wide linear
      range and can be successfully applied to determine MOX in pharmaceutical and
      biological samples with good reproducibility. The luminescence mechanism is also
      discussed in detail with ultraviolet absorption spectra.

PMID- 22133701
TI  - Switching properties of fluorescent photochromic poly(methyl methacrylate) with
      spironaphthoxazine and D-pi-A type pyran-based fluorescent dye.
AB  - Fluorescent photochromic poly(methyl methacrylate) (PMMA) with spironaphthoxazine
      (SPO) and D-pi-A type pyran-base fluorescent dye as a fluorophore was synthesized
      by typical free radical copolymerization. The poly(MMA-co-SPO-co-fluorophore) in
      both solution and solid film exhibited excellent photoregulated fluorescence
      switching behavior and reversible modulation of fluorescence intensity using
      alternating irradiation with UV and visible light. The poly(MMA-co-SPO-co
      fluorophore) also showed viscosity and conductivity switching behaviors along
      with photoresponse.

PMID- 22133702
TI  - Structural and magnetic characterization of the complete delafossite solid
      solution (CuAlO2)1-x(CuCrO2)x.
AB  - We have prepared the complete delafossite solid solution series between
      diamagnetic CuAlO(2) and the t(2g)(3)frustrated antiferromagnet CuCrO(2). The
      evolution with composition x in CuAl(1-x)Cr(x)O(2) of the crystal structure and
      magnetic properties has been studied and is reported here. The room-temperature
      unit cell parameters follow the Vegard law and increase with x as expected. The
      MU(eff) is equal to the Cr(3+) spin-only S = 3/2 value throughout the entire
      solid solution. Theta(CW) is negative, indicating that the dominant interactions
      are antiferromagnetic, and its magnitude increases with Cr substitution. For
      dilute Cr compositions, the nearest-neighbor exchange coupling constant J(BB) was
      estimated by mean-field theory to be 3.0 meV. Despite the sizable Theta(CW), long
      range antiferromagnetic order does not develop until x is almost 1, and is
      preceded by glassy behavior. The data presented here, and those on dilute Al
      substitution from Okuda et al, suggest that the reduction in magnetic frustration
      due to the presence of non-magnetic Al does not have as dominant an effect on
      magnetism as chemical disorder and dilution of the magnetic exchange. For all
      samples, the 5 K isothermal magnetization does not saturate in fields up to 5 T
      and minimal hysteresis is observed. The presence of antiferromagnetic
      interactions is clearly evident in the sub-Brillouin behavior with a reduced
      magnetization per Cr atom. An inspection of the scaled Curie plot reveals that
      significant short-range antiferromagnetic interactions occur in CuCrO(2) above
      its Neel temperature, consistent with its magnetic frustration. Uncompensated
      short-range behavior is present in the Al-substituted samples and is likely a
      result of chemical disorder.

PMID- 22133703
TI  - Comparison of laparoscopically assisted vaginal hysterectomy and abdominal
      hysterectomy: a randomized controlled trial.
AB  - OBJECTIVE: To compare intraoperative hemorrhage and other operative parameters
      after laparoscopically assisted vaginal hysterectomy (LAVH) versus total
      abdominal hysterectomy (TAH) for benign gynecologic conditions. DESIGN: A
      prospective, randomized, controlled trial. MATERIALS AND METHODS: Between April
      2010 and March 2011, 50 Thai patients with strong indications for hysterectomy-
      with uterine sizes <=16 weeks of gravid uterus and with no contraindications for
      open or laparoscopic surgeries--were randomly assigned for LAVH or TAH. MAIN
      OUTCOME MEASURES: Intraoperative blood loss, operating time, postoperative
      analgesic requirements, perioperative complications, and duration of
      hospitalization. RESULTS: Intraoperative blood loss was significantly less in the
      LAVH group (median 120 mL [range 50-300]) than in the TAH group (median 250 mL
      [105-800]) (median difference 130 mL, p <.001, 95% confidence interval [CI] 55
      200). The LAVH group required significantly less postoperative morphine sulfate
      administration (median 3 mg [range 0-12]) than the TAH group (15 mg [6-24])
      (median difference 9 mg, p <.001, 95% CI 9-12). The hospital stay for the LAVH
      group (median 3 days; range 2-7) was significantly shorter than that of the TAH
      group (median 4 days; range 4-5) (median difference 2 days, p <.001, 95% CI 1-2).
      The operating time was comparable between the 2 groups (median 100 minutes; range
      50-240) for the LAVH and 115 minutes (range 60-200) for the TAH group (median
      difference 5 minutes, p =.592, 95% CI -15-25). There were no conversions from a
      LAVH to a laparotomy. CONCLUSIONS: The LAVH has advantages over the TAH in that
      in the former there is less intraoperative blood loss, less postoperative
      morphine requirement, and a shorter duration of postoperative hospital stays.

PMID- 22133704
TI  - Duration of postoperative dressing after mini-open carpal tunnel release: a
      prospective, randomized trial.
AB  - PURPOSE: In this prospective, randomized, controlled study, we hypothesized that
      there would be no difference in short-term functional, subjective, and blinded
      wound outcome measures between patients treated after mini-open carpal tunnel
      release (CTR) with a postoperative bulky dressing for 2 weeks and those with
      dressing removal and placement of an adhesive strip after 48 to 72 hours.
      METHODS: A total of 94 consecutive patients underwent mini-open CTR and placement
      of a bulky dressing and were randomized to either bandage removal at 48 to 72
      hours with placement of an adhesive strip or continuation of the postoperative
      dressing until initial follow-up at approximately 2 weeks. We evaluated patient
      demographics, Levine-Katz scores, range of motion, strength, and a blinded
      assessment of wound healing at approximately 2 weeks and between 6 and 12 weeks.
      We conducted paired and independent sample t-tests to evaluate for statistical
      significance. RESULTS: There was no significant difference in Levine-Katz scores
      between groups at either the first follow-up or final visit. One patient with a
      longer dressing duration had evidence of a wound dehiscence. CONCLUSIONS: Removal
      of a bulky dressing after mini-open CTR and replacement with an adhesive strip at
      48 to 72 hours causes no wound complications and results in equal short-term
      clinical and subjective outcome measures compared with using a bulky dressing for
      2 weeks. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

PMID- 22133705
TI  - Role of wrist arthrodesis in patients receiving double free muscle transfers for
      reconstruction following complete brachial plexus paralysis.
AB  - PURPOSE: We reviewed 18 patients who had received double free muscle transfers
      and wrist arthrodesis to determine the effect of the stiff wrist on digital
      motion and function. METHODS: The patients were 15 men and 3 women with a mean
      age of 24 years. We determined the total active motion of the metacarpophalangeal
      and interphalangeal joints just before performing the arthrodesis and at final
      follow-up. We recorded the Disabilities of the Arm, Shoulder, and Hand functional
      score at the same times. RESULTS: All of our patients showed evidence of fusion
      at a mean of 12 +/- 2 weeks (range, 10-15 wk). The digital mean total active
      motion was 39 degrees  +/- 21 degrees  before arthrodesis and 49 degrees  +/- 25
      degrees  after arthrodesis. Preoperative Disabilities of the Arm, Shoulder, and
      Hand scores significantly decreased after fusion. Three cases were complicated
      postoperatively by wound hematoma. Five patients required wrist arthrodesis
      hardware removal because of skin irritation. CONCLUSIONS: Wrist fusion in
      patients receiving double free muscle transfers resulted in improved finger range
      of motion and overall hand function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      IV.

PMID- 22133706
TI  - Correction of forearm deformities in congenital ulnar club hand: one-bone
      forearm.
AB  - PURPOSE: To describe our experience in the correction of congenital ulnar club
      hand, using the one-bone forearm procedure. METHODS: Fifteen cases of congenital
      ulnar club hand treated at Gaslini Children's Hospital of Genoa, Italy, from 1996
      to 2008 were evaluated retrospectively. The one-bone forearm procedure was
      proposed for all 9 cases of type 2 (following the Bayne classification) and then
      performed in 8 patients with an average age of 5.5 years (range, 3-12 y). At
      surgery, the patients presented paradoxical hyperextension of the elbow (up to 45
      degrees  of extension). RESULTS: Average follow-up was 5.3 years (range, 1 to 13
      y). Union of the osteotomy was obtained in all cases. In 7 cases, union occurred
      in an average of 65 days (range, 45-90 d); in 1 case (surgery at 12 y of age),
      union was delayed, with recovery 5.5 months after surgery and no need for further
      surgical procedures. All treated cases showed improvement of forearm function and
      of grasping ability of the hand (generally tridactyl). In addition, the
      paradoxical hyperextension movement that was present before surgery disappeared
      in all patients. Long-term radiographic follow-up showed in all cases the
      formation of a structure that was morphologically similar to that of the
      previously resected radial head. CONCLUSIONS: The one-bone forearm procedure
      improves malformed forearm functions, thus increasing the possibility of carrying
      out daily life activities. The creation of the one-bone forearm should be
      preceded by the release of the distal ulnar anlage, which maintains fixed wrist
      deformity; this procedure should be performed within the first year of life.

PMID- 22133707
TI  - A national registry to determine the distribution and prevalence of Parkinson's
      disease in Thailand: implications of urbanization and pesticides as risk factors
      for Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) occurs worldwide but prior to this review of
      data from the Thailand Parkinson's Disease Registry there had been no nationwide
      PD registry reported globally. OBJECTIVE: To determine the distribution and
      prevalence of PD in Thailand and related risk factors in order to more adequately
      develop and allocate prevention and treatment resources where they are most
      needed and to ascertain risk factors that are specific to the Thai population.
      DESIGN: The Thailand Parkinson's Disease Registry is a new resource, and data
      collection began in March 2008. Data is collected by the Registry from
      physicians, and a mechanism is also provided for patients to self-report. This
      data was further analyzed by the capture-recapture methodology (CRM) to assess
      reporting biases. METHODS: The three main sources of data input to the Registry,
      i.e. (1) public hospitals, (2) private hospitals and (3) self-registration,
      require checking for duplicates and also allow estimation of completeness of
      recording (the degree of underreporting) in this disease registry. There is
      underreporting because of poor record keeping and administrative procedures in
      some facilities, and there is an unknown number of persons with PD who are not
      properly diagnosed because of inadequate facilities and staffing in some areas.
      Since our data sources should be overlapping in some way, and assuming that the
      likelihood of being detected in one system is independent of the others, we
      estimated these data sources' actual coverage and the expected total number of
      patients utilizing the 'capture-recapture' statistical technique. RESULTS: As of
      March 2011, the Thailand PD Registry had identified 40,049 PD patients. Employing
      log-linear modeling, the CRM analysis based on the three data sets estimated
      underreporting of 20,516 cases. The revised estimated total is thus 60,565 cases,
      resulting in a crude and age-adjusted prevalence of 95.34 and 424.57 PD
      cases/100,000 population, respectively. The prevalence of PD was 126.83/100,000
      in urban areas and 90.82/100,000 in rural areas (p < 0.001). Preliminary regional
      comparisons revealed a higher prevalence of PD in residents of the central plain
      valley of Thailand, an area with a large amount of pesticide use. CONCLUSIONS:
      The combination of a passive registry and the CRM technique allowed us to derive
      population prevalence estimates for PD in Thailand. Thai PD prevalence estimates
      were similar to previous ones published for Asian countries; in addition, they
      suggested that urbanization and exposure to pesticides may both be risk factors
      for PD in the Thai population.

PMID- 22133708
TI  - Bacterial pathogens associated with lung lesions in slaughter pigs from 125
      herds.
AB  - Relationships between macroscopic lesions and Polymerase Chain Reaction (PCR)
      detection of Mycoplasma hyopneumoniae (Mhp), Pasteurella multocida (Pm),
      Actinobacillus pleuropneumoniae (App), Haemophilus parasuis (Hps) and
      Streptococcus suis (Ssuis) of the lungs of 3731 slaughter pigs from 125 herds
      were assessed in France. Pneumonia and pleuritis were the most frequent lesions
      (69.3% and 15% of the lungs, respectively). Mhp, Pm, App, Ssuis and Hps were
      detected in 69.3%, 36.9%, 20.7%, 6.4% and 0.99% of the lungs, respectively. Mhp
      and Pm were associated with pneumonia at both the pig and herd levels. Pleuritis
      was not associated with any pathogen at the pig level, but was associated with a
      high percentage of pigs PCR-positive for App at the herd level. Measures focused
      on control of Mhp, Pm and App should significantly reduce the occurrence of both
      pneumonia and pleuritis.

PMID- 22133709
TI  - Percutaneous cholecystostomy for acute cholecystitis: ten-year experience.
AB  - PURPOSE: To review the clinical course of patients with acute cholecystitis
      treated by percutaneous cholecystostomy, and to identify risk factors
      retrospectively that predict outcome. MATERIALS AND METHODS: A total of 106
      patients diagnosed with acute cholecystitis were treated by percutaneous
      cholecystostomy during a 10-year period. Seventy-one (67%) presented to the
      emergency department (ED) specifically for acute cholecystitis, and 35 (23%) were
      inpatients previously admitted for other conditions. Outcomes of the two groups
      were compared with respect to severity of illness, leukocytosis, bile culture,
      liver function tests, imaging features, time intervals from onset of symptoms to
      medical and percutaneous intervention, and whether surgical cholecystectomy was
      later performed. RESULTS: Overall, 72 patients (68%) showed an improvement
      clinically, whereas 34 (32%) showed no improvement or a clinically worsened
      condition after cholecystostomy. Patients who presented to the ED primarily with
      acute cholecystitis fared better (84% of patients showed improvement) than
      inpatients (34% showed improvement; P < .0001). Gallstones were identified in 54%
      of patients who presented to the ED, whereas acalculous cholecystitis was more
      commonly diagnosed in inpatients (54%). Patients with sepsis had worse outcomes
      overall (P < .0001). Bacterial bile cultures were analyzed in 95% of patients and
      showed positive results in 52%, with no overall effect on outcome. There was no
      correlation between the time of onset of symptoms until antibiotic therapy or
      cholecystostomy in either group. Long-term outcomes for both groups were better
      for those who later underwent cholecystectomy (P < .0001). CONCLUSIONS: Outcomes
      after percutaneous cholecystostomy for acute cholecystitis are better when the
      disease is primary and not precipitated by concurrent illness.

PMID- 22133712
TI  - Mobility profiles of patients with home oxygen therapy.
AB  - Home oxygen therapy has been classically based on the use of compressed oxygen
      cylinders and portable oxygen (O(2)) concentrators. In the last few years, we
      have witnessed the advent of portable oxygen therapy equipment and liquid oxygen
      systems and even more recently portable O(2) concentrators. This equipment allows
      for greater patient mobility, which generates new issues that we must understand
      and approach adequately. One of these is selecting the best oxygen source for
      each patient. In doing so, it is necessary to compare the patient mobility
      profile with the mobility allowed by the O(2) sources in order to determine the
      degree of correlation between the two. Proper indication for home oxygen therapy,
      the selection of the right source and the titration of the oxygen flow are three
      components which we must face when deciding to prescribe home oxygen therapy. The
      patient must also cooperate with correct O(2) use.

PMID- 22133711
TI  - [Treatments of metastases in cancer].
AB  - Intravenous bisphosphonates or denosumab are a key component for the treatment of
      bone metastases. Their efficacy on the frequency and the number of skeletal
      events has been clearly shown. They also exhibit some variable activity on
      metastatic bone pain. Most often, the side effects of IV bisphosphonates are well
      tolerated. However, new and more severe side effects have also been reported,
      with an increasing incidence. These toxicities regard the bone (osteonecrosis of
      the jaw) and the kidneys (acute renal failure) and are considered a class effect
      of bisphosphonates (varying by their potency) and prevention is mandatory. Recent
      data on denosumab have led authorities to suggest no need for renal monitoring in
      patients treated with this drug. However, as renal function changes are frequent
      in cancer patients, and have implications for many treatments, we suggest that
      calculated creatinine clearance should be regularly checked.

PMID- 22133713
TI  - Latent pulmonary inflammation in patients with systemic sclerosis.
AB  - BACKGROUND: Induced sputum is a non-invasive method for studying pulmonary
      inflammation. OBJECTIVES: To assess pulmonary inflammation by analysis of induced
      sputum specimens in patients with systemic sclerosis and lung involvement, and to
      determine whether there is a correlation with the pulmonary function alterations
      in these patients. METHODS: Twenty-five patients with systemic sclerosis were
      included (20 women). Patients were divided into 3 groups according to the type of
      lung involvement: group 1, diffuse interstitial lung disease (n=10); group 2,
      those with pulmonary arterial hypertension (n=7), and group 3, patients with
      systemic sclerosis without lung involvement (n=8). All patients underwent a
      complete lung function study. Induced sputum samples were obtained and
      differential cell count was performed by optic microscopy. RESULTS: The mean
      percentage of sputum neutrophils was 85%, 71%, and 75% for groups 1, 2, and 3,
      respectively. A significant negative correlation between sputum total cell count
      and DLCO was seen in group 1 and group 3 (r=-0.733, P=.016; and r=-0.893, P=.007,
      respectively). This negative correlation was not observed in group 2.
      CONCLUSIONS: Pulmonary inflammation was present in all patients with systemic
      sclerosis included in the study, regardless of the presence of documented signs
      of pulmonary involvement. This finding suggests that induced sputum could be
      helpful for detecting early abnormalities indicative of subclinical pulmonary
      involvement in patients with systemic sclerosis.

PMID- 22133714
TI  - One-step purification of a functional, constitutively activated form of visual
      arrestin.
AB  - Desensitization of agonist-activated G protein-coupled receptors (GPCRs) requires
      phosphorylation followed by the binding of arrestin, a ~48 kDa soluble protein.
      While crystal structures for the inactive, 'basal' state of various arrestins are
      available, the conformation of 'activated' arrestin adopted upon interaction with
      activated GPCRs remains unknown. As a first step towards applying high-resolution
      structural methods to study arrestin conformation and dynamics, we have utilized
      the subtilisin prodomain/Profinity eXactTM fusion-tag system for the high-level
      bacterial expression and one-step purification of wild-type visual arrestin
      (arrestin 1) as well as a mutant form (R175E) of the protein that binds to non
      phosphorylated, light-activated rhodopsin (Rho*). The results show that both
      prodomain/Profinity eXactTM fusion-tagged wild-type and R175E arrestins can be
      expressed to levels approaching 2-3 mg/l in Luria-Bertani media, and that the
      processed, tag-free mature forms can be purified to near homogeneity using a Bio
      ScaleTM Mini Profinity eXactTM cartridge on the ProfiniaTM purification system.
      Functional analysis of R175E arrestin generated using this approach shows that it
      binds to non-phosphorylated rhodopsin in a light-dependent manner. These findings
      should facilitate the structure determination of this 'constitutively activated'
      state of arrestin 1 as well as the monitoring of conformational changes upon
      interaction with Rho*.

PMID- 22133715
TI  - Reconstitution of the human chaperonin CCT by co-expression of the eight distinct
      subunits in mammalian cells.
AB  - The eukaryotic cytosolic chaperonin CCT (chaperonin-containing TCP-1) assists
      folding of newly synthesized polypeptides. The fully functional CCT is built from
      two identical rings, each composed of single copies of eight distinct subunits.
      To study the structure and function of the CCT complex and the role of each
      subunit, a rapid and efficient method for preparing a recombinant CCT complex is
      needed. In this work, we established an efficient expression and purification
      method to obtain human recombinant CCT. BHK-21 cells were infected with a
      vaccinia virus expressing T7 RNA polymerase and transfected with eight plasmids,
      each encoding any one of the eight CCT subunits in the T7 RNA polymerase
      promoter/terminator unit. The CCT1 subunit was engineered to carry a hexa
      histidine tag or FLAG tag in the internal loop region. Three days later, cells
      were harvested for purification of the CCT complex through tag-dependent affinity
      chromatography and gel filtration. The purified recombinant CCT complexes were
      indistinguishable from the endogenous CCT purified from HeLa cells in terms of
      morphology and function. In conclusion, the co-expression system established in
      this study should be a simple and powerful tool for reconstitution of a large
      multi-subunit complex.

PMID- 22133710
TI  - Mucosal immunoglobulins and B cells of teleost fish.
AB  - As physical barriers that separate teleost fish from the external environment,
      mucosae are also active immunological sites that protect them against exposure to
      microbes and stressors. In mammals, the sites where antigens are sampled from
      mucosal surfaces and where stimulation of naive T and B lymphocytes occurs are
      known as inductive sites and are constituted by mucosa-associated lymphoid tissue
      (MALT). According to anatomical location, the MALT in teleost fish is subdivided
      into gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue
      (SALT), and gill-associated lymphoid tissue (GIALT). All MALT contain a variety
      of leukocytes, including, but not limited to, T cells, B cells, plasma cells,
      macrophages and granulocytes. Secretory immunoglobulins are produced mainly by
      plasmablasts and plasma cells, and play key roles in the maintenance of mucosal
      homeostasis. Until recently, teleost fish B cells were thought to express only
      two classes of immunoglobulins, IgM and IgD, in which IgM was thought to be the
      only one responding to pathogens both in systemic and mucosal compartments.
      However, a third teleost immunoglobulin class, IgT/IgZ, was discovered in 2005,
      and it has recently been shown to behave as the prevalent immunoglobulin in gut
      mucosal immune responses. The purpose of this review is to summarise the current
      knowledge of mucosal immunoglobulins and B cells of fish MALT. Moreover, we
      attempt to integrate the existing knowledge on both basic and applied research
      findings on fish mucosal immune responses, with the goal to provide new
      directions that may facilitate the development of novel vaccination strategies
      that stimulate not only systemic, but also mucosal immunity.

PMID- 22133716
TI  - RandoWeb, an online randomization tool for clinical trials.
AB  - This article describes RandoWeb, a generic tool allowing online randomizations
      for clinical trials. It allows some users to specify the randomization methods to
      use, patient data to collect or compute, and other users authorized to access the
      tool and their rights. Randomization can be defined through a randomization list
      or by using a dynamic method such as minimization. The randomization lists can be
      stratified and use block decomposition to maintain the best possible balance
      between the arms of the trial, even for the case when a trial is stopped
      prematurely. The block definition used by RandoWeb is slightly different from the
      classical one and, in particular, allows blocks with non-integer sizes. In
      RandoWeb, patients can be assigned up to three numbers: a record number, most
      often externally defined; a randomization number mainly useful for unblinding;
      and a treatment number used for the management of undifferentiated medicine
      packaging.

PMID- 22133717
TI  - Structural distance and evolutionary relationship of networks.
AB  - Exploring common features and universal qualities shared by a particular class of
      networks in biological and other domains is one of the important aspects of
      evolutionary study. In an evolving system, evolutionary mechanism can cause
      functional changes that forces the system to adapt to new configurations of
      interaction pattern between the components of that system (e.g. gene duplication
      and mutation play a vital role for changing the connectivity structure in many
      biological networks. The evolutionary relation between two systems can be
      retraced by their structural differences). The eigenvalues of the normalized
      graph Laplacian not only capture the global properties of a network, but also
      local structures that are produced by graph evolutions (like motif duplication or
      joining). The spectrum of this operator carries many qualitative aspects of a
      graph. Given two networks of different sizes, we propose a method to quantify the
      topological distance between them based on the contrasting spectrum of normalized
      graph Laplacian. We find that network architectures are more similar within the
      same class compared to between classes. We also show that the evolutionary
      relationships can be retraced by the structural differences using our method. We
      analyze 43 metabolic networks from different species and mark the prominent
      separation of three groups: Bacteria, Archaea and Eukarya. This phenomenon is
      well captured in our findings that support the other cladistic results based on
      gene content and ribosomal RNA sequences. Our measure to quantify the structural
      distance between two networks is useful to elucidate evolutionary relationships.

PMID- 22133718
TI  - Testing the right target and right drug at the right stage.
AB  - Alzheimer's disease (AD) is the only leading cause of death for which no disease
      modifying therapy is currently available. Recent disappointing trial results at
      the dementia stage of AD have raised multiple questions about our current
      approaches to the development of disease-modifying agents. Converging evidence
      suggests that the pathophysiological process of AD begins many years before the
      onset of dementia. So why do we keep testing drugs aimed at the initial stages of
      the disease process in patients at the end-stage of the illness?

PMID- 22133720
TI  - miRNA processing and human cancer: DICER1 cuts the mustard.
AB  - Numerous studies have implicated microRNAs (miRNAs) in cancer initiation and
      progression. In contrast, only recently has attention been focused on the pathway
      that generates these regulatory molecules. The identification of neoplasia
      associated germline mutations in DICER1 has focused translational research on
      components of the miRNA processing pathway. Deciphering of the many links between
      miRNA processing perturbations and cancer will likely provide insights into
      mechanisms of cancer control.

PMID- 22133723
TI  - A Thai reference for normal fetal nasal bone length at 11-13(+6) weeks gestation.
AB  - AIM: The purpose of this study was to establish a Thai reference for normal fetal
      nasal bone length (NBL) at 11-13(+6) weeks gestation. METHODS: The fetal nasal
      bone was measured by sonography in pregnant women at 11-13(+6) weeks gestation.
      All neonates who showed normal karyotypes were examined after delivery to confirm
      the absence of congenital abnormalities. RESULTS: A total of 255 pregnant women
      were recruited. Forty-seven pregnant women were excluded from the analysis
      because of technically unsatisfactory examination or absent nasal bone and
      chromosomal abnormalities. The mean +/- SD of NBL was 1.79 +/- 0.33 mm and
      increased significantly with crown-rump length (CRL) and gestational age (p <
      0.001). The best-fit equation for NBL in euploid fetuses in relation to CRL was:
      NBL (mm) = (0.030 * CRL (mm)) - 0.016. CONCLUSION: NBL in Thai fetuses at 11
      13(+6) weeks was found to be on average shorter than that in Caucasian, African
      American and Chinese populations, but similar to those reported in Korean and
      Latin-American populations.

PMID- 22133721
TI  - The PDL1-PD1 axis converts human TH1 cells into regulatory T cells.
AB  - Immune surveillance by T helper type 1 (T(H)1) cells is not only critical for the
      host response to tumors and infection, but also contributes to autoimmunity and
      graft-versus-host disease (GVHD) after transplantation. The inhibitory molecule
      programmed death ligand 1 (PDL1) has been shown to anergize human T(H)1 cells,
      but other mechanisms of PDL1-mediated T(H)1 inhibition such as the conversion of
      T(H)1 cells to a regulatory phenotype have not been well characterized. We
      hypothesized that PDL1 may cause T(H)1 cells to manifest differentiation
      plasticity. Conventional T cells or irradiated K562 myeloid tumor cells
      overexpressing PDL1 converted TBET(+) T(H)1 cells into FOXP3(+) regulatory T
      (T(reg)) cells in vivo, thereby preventing human-into-mouse xenogeneic GVHD
      (xGVHD). Either blocking PD1 expression on T(H)1 cells by small interfering RNA
      targeting or abrogation of PD1 signaling by SHP1/2 pharmacologic inhibition
      stabilized T(H)1 cell differentiation during PDL1 challenge and restored the
      capacity of T(H)1 cells to mediate lethal xGVHD. PD1 signaling therefore induces
      human T(H)1 cells to manifest in vivo plasticity, resulting in a T(reg) phenotype
      that severely impairs cell-mediated immunity. Converting human T(H)1 cells to a
      regulatory phenotype with PD1 signaling provides a potential way to block GVHD
      after transplantation. Moreover, because this conversion can be prevented by
      blocking PD1 expression or pharmacologically inhibiting SHP1/2, this pathway
      provides a new therapeutic direction for enhancing T cell immunity to cancer and
      infection.

PMID- 22133724
TI  - Performance gains from directed training do not transfer to untrained tasks.
AB  - Given the increasing complexity of the tasks and skills needed in modern society,
      developing effective training strategies is of tremendous practical importance.
      Furthermore, training that improves performance of both trained and untrained
      tasks would be highly efficient. In the present study, we examined how directed
      training contributes to skill acquisition, and more importantly, to engendering
      transfer of training to untrained tasks. Participants learned a complex video
      game for 30 h (Space Fortress, Donchin, Fabiani, & Sanders, 1989) using one of
      two training regimens: Hybrid Variable-Priority Training (HVT), with a focus on
      improving specific skills and managing task priority, or Full Emphasis Training
      (FET) in which participants simply practiced the game to obtain the highest
      overall score. We compared game performance, retention of training gains, and
      transfer of training to untrained tasks as a function of the training regimen.
      Compared to FET, HVT learners reached higher levels of mastery on the game and
      HVT was particularly beneficial for initially poor performing participants. This
      benefit persisted seven months after training. However, contrary to expectation,
      both HVT and FET were unsuccessful in producing transfer to untrained tasks
      compared to a group that received limited game experience, suggesting that
      directed training and practice can produce task-specific improvements, but
      improvements do not necessarily transfer from trained to untrained tasks.

PMID- 22133722
TI  - Personalized oncology through integrative high-throughput sequencing: a pilot
      study.
AB  - Individual cancers harbor a set of genetic aberrations that can be informative
      for identifying rational therapies currently available or in clinical trials. We
      implemented a pilot study to explore the practical challenges of applying high
      throughput sequencing in clinical oncology. We enrolled patients with advanced or
      refractory cancer who were eligible for clinical trials. For each patient, we
      performed whole-genome sequencing of the tumor, targeted whole-exome sequencing
      of tumor and normal DNA, and transcriptome sequencing (RNA-Seq) of the tumor to
      identify potentially informative mutations in a clinically relevant time frame of
      3 to 4 weeks. With this approach, we detected several classes of cancer mutations
      including structural rearrangements, copy number alterations, point mutations,
      and gene expression alterations. A multidisciplinary Sequencing Tumor Board (STB)
      deliberated on the clinical interpretation of the sequencing results obtained. We
      tested our sequencing strategy on human prostate cancer xenografts. Next, we
      enrolled two patients into the clinical protocol and were able to review the
      results at our STB within 24 days of biopsy. The first patient had metastatic
      colorectal cancer in which we identified somatic point mutations in NRAS, TP53,
      AURKA, FAS, and MYH11, plus amplification and overexpression of cyclin-dependent
      kinase 8 (CDK8). The second patient had malignant melanoma, in which we
      identified a somatic point mutation in HRAS and a structural rearrangement
      affecting CDKN2C. The STB identified the CDK8 amplification and Ras mutation as
      providing a rationale for clinical trials with CDK inhibitors or MEK (mitogen
      activated or extracellular signal-regulated protein kinase kinase) and PI3K
      (phosphatidylinositol 3-kinase) inhibitors, respectively. Integrative high
      throughput sequencing of patients with advanced cancer generates a comprehensive,
      individual mutational landscape to facilitate biomarker-driven clinical trials in
      oncology.

PMID- 22133725
TI  - The processes of facilitation and inhibition in a cue-target paradigm: insight
      from movement trajectory deviations.
AB  - Several researchers have examined the trajectories of aiming movements in cue
      target paradigms to investigate the motoric and attentional underpinnings of the
      inhibition of return (IOR) effect. The results of separate studies have revealed
      inconsistent patterns of trajectory deviations. These discrepancies may have
      arisen because the studies used narrow ranges of cue-target onset asynchronies
      (CTOAs) which may have prevented the time courses of facilitation and inhibition
      effects to be fully assessed. The present study was designed to conduct an
      examination of temporal and spatial characteristics of aiming movements over a
      broader range of CTOAs to provide a more comprehensive assessment of the
      potential expression of attentional and motoric contributions to cuing effects.
      Participants aimed to targets which were preceded by a non-predictive cue at
      CTOAs of 100, 350, 850, and 1100 ms. Analysis of spatial and temporal
      characteristics of the movements revealed facilitatory and inhibitory cuing
      effects in the trajectories, but only inhibitory cuing effects in RT. Further,
      the inhibitory effects in RT appeared at a shorter CTOA than the inhibitory
      effects in trajectories. This pattern of results suggests that the inhibitory
      mechanisms underlying IOR affect both attention and motor systems, but that these
      effects are displaced in time.

PMID- 22133726
TI  - Medication safety in the neonatal intensive care unit: position statement #3055.

PMID- 22133727
TI  - The effect of staff nurses' shift length and fatigue on patient safety: position
      statement #3054.

PMID- 22133728
TI  - Electric-field controlled liposome formation with embedded superparamagnetic iron
      oxide nanoparticles.
AB  - Liposomes are one of the most promising biomaterial carriers to deliver DNA,(1)
      proteins, drugs and medicine in human bodies. However, artificially formed
      liposomes have to satisfy some crucial functions such as: (i) to efficiently
      carry drugs to targeted systems, (ii) to be biologically stable until they are
      removed from human body, (iii) to be biodegradable, and (iv) to be sufficiently
      small in size for effective drug delivery. Here, we report an efficient and novel
      method to simultaneously manufacture and incorporate super-paramagnetic iron
      oxide nanoparticles (efficient target finder in the presence of external magnetic
      field) into the liposome's interior and its bilayer. In this technique, we use
      electric field to control the formation of liposomes and the incorporation of
      iron oxide nanoparticles. Our preparation procedure does not require any chemical
      or ultrasound treatments. Apart from that, we also provide further experimental
      investigations on the role of electric fields on the formation of liposomes using
      XPS(2) and the magnetic-optical microscope.

PMID- 22133729
TI  - Pyrene as a membrane depth gauge: wavelength selective fluorescence approach to
      monitor pyrene localizations in the membrane.
AB  - We take the advantage of pyrene's unique spectral properties as a reliable
      polarity indicator to monitor pyrene localizations in the membrane depth by using
      wavelength selective fluorescence approach. We show that fine structure of pyrene
      fluorescence emission spectra and excimerization rate in model and native
      phospholipid membranes depend on the excitation wavelength. This phenomenon is
      not observed in neat solvents. In membranes, the dependence on the excitation
      wavelength reflects selective excitation of pyrene molecules located close to the
      membrane-water polar interface, or deep in the hydrophobic core of the membrane,
      verified with the aid of pyrene derivatives of fatty acids of various lengths.

PMID- 22133731
TI  - Optical coherence tomography for rapid tissue screening and directed histological
      sectioning.
AB  - In pathology, histological examination of the "gold standard" to diagnose various
      diseases. It has contributed significantly toward identifying the abnormalities
      in tissues and cells, but has inherent drawbacks when used for fast and accurate
      diagnosis. These limitations include the lack of in vivo observation in real time
      and sampling errors due to limited number and area coverage of tissue sections.
      Its diagnostic yield also varies depending on the ability of the physician and
      the effectiveness of any image guidance technique that may be used for tissue
      screening during excisional biopsy. In order to overcome these current
      limitations of histology-based diagnostics, there are significant needs for
      either complementary or alternative imaging techniques which perform non
      destructive, high resolution, and rapid tissue screening. Optical coherence
      tomography (OCT) is an emerging imaging modality which allows real-time cross
      sectional imaging with high resolutions that approach those of histology. OCT
      could be a very promising technique which has the potential to be used as an
      adjunct to histological tissue observation when it is not practical to take
      specimens for histological processing, when large areas of tissue need
      investigating, or when rapid microscopic imaging is needed. This review will
      describe the use of OCT as an image guidance tool for fast tissue screening and
      directed histological tissue sectioning in pathology.

PMID- 22133730
TI  - Quantitation of human herpesvirus-6A, -6B and -7 DNAs in whole blood, mononuclear
      and polymorphonuclear cell fractions from healthy blood donors.
AB  - BACKGROUND: Diagnosis of human herpesvirus-6A (HHV-6A), -6B (HHV-6B) or -7 (HHV
      7) infections is often based on the measure of viral load in blood. OBJECTIVES:
      The aim of this study was to define usual values of HHV-6A, HHV-6B and HHV-7
      loads in blood fractions (whole blood [WB], mononuclear cells [PBMCs],
      polymorphonuclear leukocytes [PMNLs]) of blood donors. STUDY DESIGN: HHV-6A, HHV
      6B and -7 DNAs were quantitated using real-time PCR assays in WB, PBMCs and PMNLs
      separated on Ficoll or dextran gradients, respectively, for 200 blood donors.
      Viral loads were expressed as the number of viral genomic copies per million
      cells (Cop/M) for all fractions, and also per milliliter for WB. RESULTS: HHV-6B
      DNA was rarely detected in WB (8%), PBMCs (16.5%), and PMNLs (10.5%), HHV-6A was
      never detected, whereas HHV-7 DNA was often present in WB (51.5%), PBMCs (62%)
      and PMNLs (51.5%). Median loads were low with 81 Cop/M in WB, 62 Cop/M in PBMCs
      and 34.5 Cop/M in PMNLs for HHV-6B, and 129 Cop/M in WB, 225 Cop/M in PBMCs and
      62 Cop/M in PMNLs for HHV-7. Viral load expression per million cells and per mL
      were equivalent. One subject had chromosomally integrated HHV-6 with high viral
      loads ranging from 2.23*10(6) to 3.21*10(6) Cop/M in all compartments and plasma.
      CONCLUSIONS: These results allow to propose viral load in WB as a sensitive and
      suitable marker, with values for healthy subjects at approximately 100 Cop/M for
      both viruses. The prevalence of chromosomally integrated HHV-6 was 0.5%.

PMID- 22133732
TI  - Predictors of periprocedural brain lesions associated with carotid stenting.
AB  - BACKGROUND: Carotid stenting carries a risk of periprocedural stroke. We aimed at
      determining predictors of cerebral ischemic events associated with stenting for
      symptomatic carotid stenosis. METHODS: 127 patients who had been studied by
      diffusion-weighted MR imaging (DWI) before and on the day after carotid stenting
      were included. Six clinical variables and 5 variables characterizing the target
      carotid artery and aortic atherosclerosis were analyzed as potential risk factors
      for new ipsilateral DWI lesions after stenting. RESULTS: Among all variables
      assessed, only age, length of stenosis and carotid intima-media thickness (IMT)
      significantly modified the risk of new lesions after stenting. Age >=68 years,
      stenosis >=15 mm and IMT >=1.3 mm were identified as the best thresholds to
      predict new lesions. In the subgroup of patients >=68 years with carotid stenosis
      >=15 mm in length and IMT >=1.3 mm, the risk of new lesions was markedly higher
      than in patients to whom no more than two of these factors applied (odds ratio
      7.250, 95% CI 1.612-34.513, p = 0.005). The use of this simple predictive model
      correctly identified patients who had new lesions after stenting with high
      specificity (0.96) and a negative predictive value (0.83), while the positive
      predictive value was moderate (0.60) and sensitivity was low (0.23). CONCLUSIONS:
      The risk of stenting for symptomatic carotid stenosis may vary with clinical and
      morphological patient characteristics. Further research is needed to validate
      these results and to evaluate the safety of stenting versus endarterectomy in
      specific patient subgroups.

PMID- 22133733
TI  - Prevalence of multiple sclerosis: door-to-door survey in three rural areas of
      coastal Black Sea regions of Turkey.
AB  - BACKGROUND: Little information exists on multiple sclerosis (MS) in Turkey. With
      a door-to-door survey in an urban part of Istanbul, we recently reported a
      prevalence rate of 101/100,000 population. We therefore investigated three rural
      areas of Turkey at the same latitude. METHODS: The same survey methods were used
      for total populations of two rural areas (Kandira and Geyve) near Istanbul, and
      for half the population of Erbaa, all near 40 degrees  north latitude on the
      Black Sea coast. RESULTS: In Kandira, 5 of 8 suspects were diagnosed as having MS
      among 8,171 screened, resulting in a prevalence rate of 61/100,000. Geyve with 7
      MS cases in 17,016 screened had a prevalence of 41/100,000, and Erbaa with 15 MS
      cases in 28,177 screened one of 53/100,000. Together they showed a prevalence of
      51/100,000. Of the 27 patients, 20 were women; 25 had definite and 2 possible MS,
      the former all with abnormal laboratory findings. Average ages were 30.5 years at
      onset and 39.1 years at diagnosis. Clinical features and course were typical of
      European MS. CONCLUSION: These findings indicate that Turkey is a high-risk MS
      area, similar to most regions of Mediterranean Europe, where all recent increases
      are likely due to (undefined) environmental factors.

PMID- 22133734
TI  - [Management of chemotherapy in hemodialysis patients].
AB  - BACKGROUND: The increased incidence of cancer in dialysis patients has been
      discussed since the mid-70s. Consequently, oncologists, nephrologists and
      pharmacists are increasingly facing challenging situations of cytotoxic drug
      handling in dialysis patients. In dialysis patients, two main issues must be
      considered. First, renal function of hemodialysis (HD) patients is no longer
      functional. Therefore, these patients may necessitate drug dosage reduction,
      namely drug prescription, must be cautiously checked before administration with
      appropriate dosage adjustment whenever necessary to ensure efficacy while
      avoiding overdosage and related side effects. Secondly, drug clearance by
      dialysis must be taken into account for appropriate chemotherapy timing in order
      to avoid drug removal, which may result in a loss of efficacy. METHODS: We
      reviewed the international literature on the pharmacokinetics, efficacy,
      tolerance and dosage adjustment of anticancer drugs used on hemodialysis cancer
      patients, using the key words: kidney, renal, dialysis, hemodialysis, end-stage
      renal disease and the name of each drug. RESULTS: Only case reports and small
      series were found. 57.1% of the drugs need dosage adjustment and 64.3% should be
      administered after the dialysis session. CONCLUSION: Cancer treatment in feasible
      in dialysis patients. Some drugs require dosage adaptation while others can be
      given as in patients with normal kidney function. These patients need coordinated
      care between oncologists, nephrologists and pharmacists to optimize drug delivery
      and logistics. Frailty scores, like in oncogeriatrics, should be built to
      optimally adapt cancer treatments in these dialysis patients.

PMID- 22133735
TI  - Ultrasonic-assisted manufacturing processes: variational model and numerical
      simulations.
AB  - We present a computational study of ultrasonic assisted manufacturing processes
      including sheet metal forming, upsetting, and wire drawing. A fully variational
      porous plasticity model is modified to include ultrasonic softening effects and
      then utilized to account for instantaneous softening when ultrasonic energy is
      applied during deformation. Material model parameters are identified via inverse
      modeling, i.e. by using experimental data. The versatility and predictive ability
      of the model are demonstrated and the effect of ultrasonic intensity on the
      manufacturing process at hand is investigated and compared qualitatively with
      experimental results reported in the literature.

PMID- 22133736
TI  - Focused, phased-array plane piston and spherically-shaped concave piston
      transducers: comparison for the same aperture and focal point.
AB  - It has sometimes been assumed that the phased-array plane piston transducer and
      the spherically-shaped concave piston transducer are equivalent structures when
      both have the same aperture and focal point. This assumption has not been
      previously examined, nor has an expression for the on-axis impulse response of
      the focused, phased-array plane piston transducer been derived. It is shown in
      this paper how such an expression can be obtained. Comparisons of the impulse
      response for both structures show similarities, as well as some differences that
      could be significant as the observation point approaches the focal point.
      Comparisons are also performed for wide-band pulses close to the focus as well as
      for sinusoidal excitation. A physical explanation for the cause of the impulse
      response discrepancy is shown to be due to the nature of the piston focusing
      delay and its effect on the Rayleigh integral.

PMID- 22133737
TI  - A preliminary in vitro assessment of polymer-shelled microbubbles in contrast
      enhanced ultrasound imaging.
AB  - This paper focuses on the use of poly (vinyl alcohol)-shelled microbubbles as a
      contrast agent in ultrasound medical imaging. The objective was an in vitro
      assessment of the different working conditions and signal processing methods for
      the visual detection (especially in small vessels) of such microbubbles, while
      avoiding their destruction. Polymer-shelled microbubbles have recently been
      proposed as ultrasound contrast agents with some important advantages. The major
      drawback is a shell that is less elastic than that of the traditional lipidic
      microbubbles. Weaker echoes are expected, and their detection at low
      concentrations may be critical. In vitro experiments were performed with a
      commercial ultrasound scanner equipped with a dedicated acquisition board. A
      concentration of 100bubbles/mm(3), excitation pressure amplitudes from 120kPa to
      320kPa, and a central frequency of 3MHz or 4.5MHz were used. Three multi-pulse
      techniques (i.e., pulse inversion, contrast pulse sequence based on three
      transmitted signals, and contrast pulse sequence in combination with the chirp
      pulse) were compared. The results confirmed that these microbubbles produce a
      weaker ultrasound response than lipidic bubbles with a reduced second-order
      nonlinear component. Nevertheless, these microbubbles can be detected by the
      contrast pulse sequence technique, especially when the chirp pulse is adopted.
      The best value of the contrast-to-tissue ratio was obtained at an excitation
      pressure amplitude of 230kPa: although this pressure amplitude is higher than
      what is typically used for lipidic microbubbles, it does not cause the rupture of
      the polymeric contrast agent.

PMID- 22133738
TI  - [Treatment of resistant Gram-positive bacterial infections].

PMID- 22133739
TI  - [Epidemiology of bacterial resistance, mycobacteria, vaccinations, antifungals,
      viral infections].

PMID- 22133740
TI  - Screening for NOTCH3 gene mutations among 151 consecutive Korean patients with
      acute ischemic stroke.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is a single-gene disorder of cerebral small
      blood vessels caused by mutations in the NOTCH3 gene. The initial detection of
      CADASIL may be more difficult among Asian populations because common clinical
      phenotypes and neuroimaging findings are not frequently found in these
      populations. The purpose of this study was to screen the NOTCH3 gene for
      mutations among consecutive patients with acute ischemic stroke from our region
      in Korea. METHODS: Between April 2008 and March 2009, 151 consecutive patients
      with acute ischemic stroke were screened for NOTCH3 mutations. All patients
      underwent a detailed clinical examination and structured interview for clinical
      symptoms and family history. We reviewed brain magnetic resonance imaging data
      from stroke patients to assess the severity of white-matter hyperintensity
      lesions, the number of cerebral microbleeds, and the number of lacunar
      infarctions. Polymerase chain reaction was used to screen exons 3, 4, 6, 11, and
      18 of the NOTCH3 gene. RESULTS: Among 151 consecutive patients with acute
      ischemic stroke, 6 patients (4.0%; 95% confidence interval [CI] 0.9-7.1)
      possessed a NOTCH3 gene mutation. All patients exhibited the same R544C mutation
      in exon 11. Four of these 6 patients presented with large artery atherosclerosis.
      The prevalence of CADASIL in patients with neuroimaging features consistent with
      advanced small-vessel disease was 36.0% (95% CI 8.0-64.8). CONCLUSIONS: In this
      region, NOTCH3 gene mutations are frequently found in acute stroke patients who
      present with neuroimaging features consistent with advanced small-vessel disease.

PMID- 22133741
TI  - A case of embolic stroke imitating atherothrombotic brain infarction before
      massive hemorrhage from an infectious aneurysm caused by Streptococci.
AB  - Early detection followed by treatment with antibiotics in conjunction with direct
      or endovascular surgery is integral in the management of patients with
      intracranial infectious aneurysms. These aneurysms often manifest as massive
      intracranial hemorrhages, which severely deteriorate the outcome. It is very
      important to detect infectious aneurysms before they rupture. Although usually
      associated with infective endocarditis, these aneurysms can occur in a variety of
      clinical settings. We present a case of alpha-Streptococcus-provoked infectious
      aneurysm in a patient without infective endocarditis, initially presenting as
      atherothrombotic-like brain infarction, before massive intracranial hemorrhage.
      The present case alerts clinicians to keep in mind possible development of
      infectious aneurysms, even in patients who appear to be suffering from
      atherothrombotic stoke, especially in patients presenting with signs of
      infection.

PMID- 22133743
TI  - Recurrent lobar intracerebral hemorrhage in Tangier disease.
AB  - We report a patient with familial alpha-lipoprotein deficiency (Tangier disease)
      who presented with recurrent lobar intracerebral hemorrhages and accumulating
      microbleeds on T*2-weighted magnetic resonance imaging, suggestive of probable
      cerebral amyloid angiopathy. This case provides new insight into the links
      between the adenotriphosphate-binding cassette A1 (ABCA1) transporter gene
      mutation in Tangier disease and apolipoprotein-E expression in the brain and
      supports further investigation of the potential role of ABCA1 transporter in
      cerebral amyloid angiopathy.

PMID- 22133742
TI  - Wake-up stroke within 3 hours of symptom awareness: imaging and clinical features
      compared to standard recombinant tissue plasminogen activator treated stroke.
AB  - BACKGROUND: Patients with wake-up stroke (WUS) are excluded from thrombolysis
      because of unknown time of symptom onset. Previous studies have reported similar
      stroke severity and early ischemic changes (EICs) in patients with WUS and stroke
      of known onset. These studies, however, included patients within a large
      timeframe to imaging or did not quantify EICs. The aim of our study was to
      quantify EICs of patients with WUS presenting within 3 hours of symptom
      recognition compared to standard 3-hours recombinant tissue plasminogen activator
      (rt-PA)-treated patients and assess the extent of ischemic lesion and functional
      independence at follow-up. METHODS: Patients were selected from our prospectively
      collected stroke database. Baseline and follow-up computed tomographic scans were
      graded with Alberta Stroke Program Early Computed Tomography Score (ASPECTS).
      Clinical outcome measures were modified Rankin Scale score, mortality, and
      symptomatic intracerebral hemorrhage. RESULTS: Demographic features, risk
      factors, stroke severity, and baseline ASPECTS were similar in both groups. WUS
      and rt-PA-treated patients had similar tissue outcome (median ASPECTS 7.0 vs 7.5;
      P = .202). Functional outcome was more favorable in rt-PA-treated patients (61.6%
      vs 43.1%; odds ratio [OR] 2.12; 95% confidence interval [CI] 1.05-4.28; P =
      .037). After adjusting for age, stroke severity, treatment, and EICs in less than
      one-third of middle cerebral artery territory, rt-PA and National Institutes of
      Health Stroke Scale scores remained the only significant predictors of outcome
      (OR 7.76; 95% CI 2.40-25.05; P = .001 and OR 0.74; 95% CI 0.67-0.82; P < .001,
      respectively). CONCLUSIONS: Within 3 hours of symptom recognition, patients with
      WUS have EICs similar to rt-PA-treated patients. It is reasonable to expect that
      selected WUS patients might benefit from thrombolysis within 3 hours of symptom
      awareness.

PMID- 22133744
TI  - Clinical evaluation of lacunar infarction and branch atheromatous disease.
AB  - Patients with branch atheromatous disease (BAD) are more likely to experience
      neurologic deficits compared with those with lacunar infarction (LI), although
      both disorders are forms of intracranial deep brain infarction. We clinically
      evaluated patients with BAD (n = 42) and LI (n = 57) to investigate why patients
      with BAD tend to experience progressing stroke. Patients presenting to our
      hospital with acute ischemic stroke between April 2008 and March 2009 were
      screened. LI was defined as an intracerebral lesion <15 mm in diameter and fewer
      than 3 slices or a lesion within the pontine parenchyma. BAD was defined as an
      intracerebral lesion of >= 15 mm in diameter and more than 3 slices or a lesion
      extending to the surface of the pontine base observed on diffusion-weighted
      magnetic resonance imaging. Progressing stroke was defined as a >2-point increase
      in the National Institutes of Health Stroke Scale within 48 hours of stroke
      onset. Progressing stroke was significantly more prevalent in the BAD group
      compared with the LI group (38.1% vs 12.3%). Diabetes mellitus with a high low
      density lipoprotein level was significantly prevalent in patients with
      progressing BAD. When BAD in the cerebrum and BAD in the pons were analyzed
      separately, a low-density lipoprotein level >140 mg/dL was the most prevalent
      risk factor for progressing BAD in the cerebrum, and patient age was the
      strongest risk factor for progressing BAD in the pons. Vascular lesions asvsessed
      by magnetic resonance angiography were significantly abundant in both progressing
      LI and BAD. Our findings suggest that BAD may have a poorer prognosis than LI.
      Poorly controlled diabetes and hyperlipidemia could lead to atherosclerosis of
      the branch artery, resulting in worsening of BAD.

PMID- 22133745
TI  - Construction of theta-type shuttle vector for Leuconostoc and other lactic acid
      bacteria using pCB42 isolated from kimchi.
AB  - The pCB42 plasmid from Leuconostoc citreum CB2567, a strain isolated from kimchi,
      was characterized, and a shuttle vector for Escherichia coli and lactic acid
      bacteria (LAB) was constructed. The pCB42 plasmid has a circular structure of
      4312bp, a low G+C content, and no single-stranded DNA intermediates during
      replication, which indicates that pCB42 replicates via the theta-type replication
      mechanism. In silico analysis of this plasmid revealed 6 open reading frames: 1
      transposase gene, 1 DNA-binding gene, 2 putative replication genes, and 2 unknown
      genes. The fragment encompassing ORF5 contains a functional plasmid replicon.
      This plasmid was capable of replicating in various LAB, including L. citreum, L.
      mesenteroides, Lactobacillus plantarum, Lb. reuteri, Lactococcus lactis,
      Streptococcus thermophilus, Weissella confusa, and Oenococcus oeni. The LAB-E.
      coli shuttle vector was constructed by ligating pCB42 and pEK104, and the
      resulting shuttle vector, pLeuCM42, showed a high segregational stability in L.
      citreum CB2567 after 100 generations of cell division. By using this shuttle
      vector, the beta-gal gene from Lb. plantarum was successfully expressed in the
      host strain, L. citreum CB2567. The pLeuCM42 shuttle vector can serve as a useful
      gene-delivery and expression tool for the genetic study or metabolic engineering
      of various strains of LAB.

PMID- 22133746
TI  - Protein phosphorylation involved in the gene expression of the hydrogen sulphide
      producing enzyme cystathionine gamma-lyase in the pancreatic beta-cell.
AB  - Cystathionine gamma-lyase (CSE) is one of the major enzymes for the production of
      hydrogen sulphide (H(2)S), a multifunctional gasotransmitter in the pancreatic
      beta-cell. We examined the mechanisms by which glucose induces CSE expression in
      mouse pancreatic islets and the insulin-secreting cell line MIN6. CSE expression
      was increased by anti-diabetic sulphonylureas, and decreased by the ATP-sensitive
      K(+)-channel opener diazoxide and the voltage-dependent Ca(2+) channel blocker
      nitrendipine. Application of the synthetic inhibitors of protein kinases revealed
      the involvement of Ca(2+)/calmodulin-dependent protein kinase (CaMK) II and
      extracellular signal-regulated protein kinase (ERK) in glucose- and thapsigargin
      induced CSE expression. The CaMK IIdelta knockdown also suppressed CSE
      expression. Knockdown of the transcription factors Sp1 and Elk1, both of which
      can be phosphorylated by ERK, blunted CSE expression. By a reporter assay, we
      found Sp1 may directly and Elk1 may indirectly regulate CSE expression. These
      findings suggest Ca(2+)-dependent CSE expression may be mediated via protein
      phosphorylation of Sp1 and Elk1 in pancreatic beta-cells.

PMID- 22133747
TI  - Conversion from the "oncogene addiction" to "drug addiction" by intensive
      inhibition of the EGFR and MET in lung cancer with activating EGFR mutation.
AB  - Emergence of acquired resistance is virtually inevitable in patients with a
      mutation in the epidermal growth factor receptor gene (EGFR) treated with EGFR
      tyrosine kinase inhibitors (TKIs). Several novel TKIs that may prevent or
      overcome the resistance mechanisms are now under clinical development. However,
      it is unknown how tumor cells will respond to intensive treatment using these
      novel TKIs. We previously established HCC827EPR cells, which are T790M positive,
      through combined treatment with erlotinib and a MET-TKI from erlotinib
      hypersensitive HCC827 cells. In this study, we treated HCC827EPR cells
      sequentially with an irreversible EGFR-TKI, CL-387,785, to establish resistant
      cells (HCC827CLR), and we analyzed the mechanisms responsible for resistance. In
      HCC827CLR cells, PTEN expression was downregulated and Akt phosphorylation
      persisted in the presence of CL-387,785. Akt inhibition restored CL-387,785
      sensitivity. In addition, withdrawal of CL-387,785 reduced cell viability in
      HCC827CLR cells, indicating that these cells were "addicted" to CL-387,785.
      HCC827CLR cells overexpressed the EGFR, and inhibition of the EGFR or MEK-ERK was
      needed to maintain cell proliferation. Increased senescence was observed in
      HCC827CLR cells in the drug-free condition. Through long-term culture of
      HCC827CLR cells without CL-387,785, we established HCC827-CL-387,785-independent
      cells, which exhibited decreased EGFR expression and a mesenchymal phenotype. In
      conclusion, PTEN downregulation is a newly identified mechanism underlying the
      acquired resistance to irreversible EGFR-TKIs after acquisition of T790M against
      erlotinib. This series of experiments highlights the flexibility of cancer cells
      that have adapted to environmental stresses induced by intensive treatment with
      TKIs.

PMID- 22133749
TI  - Acute brucellosis with myelodysplastic syndrome presenting as pancytopenia and
      Fever of unknown origin.
AB  - OBJECTIVE: To report a rare case of brucellosis with myelo-dysplastic syndrome
      (MDS). CLINICAL PRESENTATION AND INTERVENTION: A 70-year-old woman presented with
      pancytopenia and fever of unknown origin (FUO). The initial diagnosis was
      brucellosis; the woman was treated with doxycycline and rifampin against Brucella
      melitensis but was later diagnosed as suffering from MDS. She was immediately
      transferred to the Department of Hematology for further evaluation. CONCLUSION:
      This study highlights the rarity of brucellosis with MDS, and we recommend that
      brucellosis with MDS be considered in patients presenting with pancytopenia and
      FUO.

PMID- 22133748
TI  - You can count on the motor cortex: finger counting habits modulate motor cortex
      activation evoked by numbers.
AB  - The embodied cognition framework suggests that neural systems for perception and
      action are engaged during higher cognitive processes. In an event-related fMRI
      study, we tested this claim for the abstract domain of numerical symbol
      processing: is the human cortical motor system part of the representation of
      numbers, and is organization of numerical knowledge influenced by individual
      finger counting habits? Developmental studies suggest a link between numerals and
      finger counting habits due to the acquisition of numerical skills through finger
      counting in childhood. In the present study, digits 1 to 9 and the corresponding
      number words were presented visually to adults with different finger counting
      habits, i.e. left- and right-starters who reported that they usually start
      counting small numbers with their left and right hand, respectively. Despite the
      absence of overt hand movements, the hemisphere contralateral to the hand used
      for counting small numbers was activated when small numbers were presented. The
      correspondence between finger counting habits and hemispheric motor activation is
      consistent with an intrinsic functional link between finger counting and number
      processing.

PMID- 22133750
TI  - Risk factors and effects on long-term outcomes of cardiac troponin I elevation
      after drug-eluting stent implantation in patients with stable coronary artery
      disease.
AB  - This study evaluated the risk factors of postprocedure cardiac troponin I (cTnI)
      increase and its effects on repeat revascularization and on overall clinical
      outcomes in patients with angina and normal preprocedural cTnI levels who
      underwent successful drug-eluting stent implantation. Postprocedure cTnI increase
      (>=0.5 ng/ml) was observed in 207 of 802 patients (25.8%). Patients with cTnI
      increase had more extensive coronary disease than patients without cTnI increase,
      which necessitated for the cTnI group more multilesion interventions and a longer
      total stent length. In multivariate analysis, total stent length (odds ratio
      1.02, 1.01 to 1.03, p = 0.001) and use of glycoprotein IIb/IIIa inhibitors (3.07,
      1.54 to 6.11, p <0.001) were identified as independent predictors of cTnI
      increase. During a median follow-up of 42 months, however, there were no
      significant between-group differences in Kaplan-Meier estimates of any repeat
      revascularization (24.8% vs 18.4%, hazard ratio 1.085, 0.723 to 1.627, p = 0.694)
      and major adverse cardiovascular events (27.0% vs 22.4%, 1.022, 0.703 to 1.485, p
      = 0.911). In conclusion, patients with postprocedure cTnI increase had more
      severe baseline coronary disease and received more complex interventional
      procedures. However, cTnI increase after successful drug-eluting stent
      implantation was not associated with an increased risk of repeat
      revascularization or of other adverse events.

PMID- 22133751
TI  - Ventricular dyssynchrony of idiopathic versus pacing-induced left bundle branch
      block and its prognostic effect in patients with preserved left ventricular
      systolic function.
AB  - The extent of left ventricular (LV) dyssynchrony might not be comparable between
      right ventricular pacing-induced left bundle branch block (RV-LBBB) and
      idiopathic LBBB (iLBBB), despite the morphologic analogy on the
      electrocardiogram. The objectives of the present study were to elucidate the
      differences in the LV dyssynchrony index (LVdys) between RV-LBBB and iLBBB, and
      to assess the prognostic implication of LV dyssynchrony. The conventional
      echocardiographic parameters, LVdys, and LV end-systolic wall stress were
      evaluated in 20 healthy volunteers and 21 patients with iLBBB and 20 with RV-LBBB
      with preserved LV systolic function. Three types of LVdys were evaluated: LVdys
      6, LVdys-2, and LVdys-standard deviation. The patients were clinically followed
      up for about 3 years. The prevalence of LV dyssynchrony was not rare in those
      with either iLBBB or RV-LBBB, but it was more prevalent in the patients with
      iLBBB than in those with RV-LBBB. The patients with iLBBB had greater LVdys than
      those with RV-LBBB (84 +/- 55 vs 55 +/- 50 for LVdys-6, 51 +/- 49 vs 31 +/- 40
      for LVdys-2, 37 +/- 24 vs 24 +/- 22 for LVdys-standard deviation in iLBBB vs RV
      LBBB). LVdys displayed significant correlations with QRS duration, LV volumes, LV
      ejection fraction, LV end-systolic wall stress, and mitral inflow E/mitral
      annular E' velocity ratio. Multivariate logistic regression analysis showed that
      the LV end-diastolic volume and LV end-systolic wall stress were independent
      determinants of the presence of LV dyssynchrony. During follow-up, no
      cardiovascular death or hospitalization for heart failure was reported in either
      group. In conclusion, despite similarities in electrocardiographic morphology,
      the extent of LV dyssynchrony were greater in patients with iLBBB, with LV
      preload and afterload the main determinants. No association was found between the
      presence of LV dyssynchrony and prognosis.

PMID- 22133752
TI  - Comparison of aortic dissection in korean patients with versus without the marfan
      syndrome.
AB  - Among the cardiovascular manifestations in the Marfan syndrome (MFS), aortic
      dissection stands out as a major cause of early mortality. The aim of this study
      was to test the hypothesis that patients with the MFS who experience aortic
      dissection differ in clinical features and outcomes from those with aortic
      dissection not related to the MFS. Data from patients diagnosed with aortic
      dissection from December 1994 to March 2009 at 1 of the major medical centers in
      Korea were reviewed. The clinical presentations, dissection characteristics, and
      outcomes of patients with and those without the MFS in a Korean population were
      compared. Of 445 patients with aortic dissection, 46 (10%) had the MFS. Compared
      to non-MFS patients, those with the MFS developed aortic dissection at younger
      ages (33 +/- 10 vs 57 +/- 13 years, p <0.001) and were less frequently
      hypertensive (11% vs 73%, p <0.001). During the follow-up period, patients with
      the MFS more often developed aortic dilatation and expansion of the dissection
      (39% vs 18%, p = 0.003) and showed a higher rate of reoperation (30% vs 9%, p
      <0.001). In conclusion, in Korean patients, aortic dissection with the MFS had
      different characteristics and poorer outcomes than aortic dissection without the
      MFS. These findings underscore the importance of accurate diagnosis and
      surveillance of this condition in the MFS.

PMID- 22133753
TI  - Usefulness of transesophageal echocardiography to confirm clinical utility of
      CHA2DS2-VASc and CHADS2 scores in atrial flutter.
AB  - The CHA(2)DS(2)-VASc and CHADS(2) risk stratification schemes are used to predict
      thromboembolism and ischemic stroke in patients with atrial fibrillation.
      However, limited data are available regarding the utility of these risk
      stratification schemes for stroke in patients with atrial flutter. A
      retrospective analysis of 455 transesophageal echocardiographic studies in
      patients with atrial flutter was performed to identify left atrial (LA) thrombi
      and/or spontaneous echocardiographic contrast (SEC). The CHA(2)DS(2)-VASc
      (Congestive heart failure, Hypertension, Age >=75 years [doubled risk weight],
      Diabetes mellitus, previous Stroke/transient ischemic attack [doubled risk
      weight], Vascular disease, Age 65 to 74 years, Sex) and CHADS(2) (Congestive
      heart failure, Hypertension, Age >=75 years, Diabetes mellitus, previous
      Stroke/transient ischemic attack [double risk weight]) scores were calculated to
      stratify the risk of stroke or transient cerebrovascular ischemic events.
      Transesophageal echocardiography revealed LA thrombi in 5.3% and SEC in 25.9% of
      patients. Using CHADS(2), LA thrombus was found in 2.2% of the low-intermediate
      risk group and 8.3% of the high-risk group (p = 0.005). SEC was found in 19.8% of
      the low-intermediate-risk group and 32% of the high-risk group (p = 0.004). Using
      CHA(2)DS(2)-VASc, LA thrombus was found in 1.7% of the low-intermediate-risk
      group and 6.5% of the high-risk group (p = 0.053). SEC was found in 11.8% of the
      low-intermediate-risk group versus 30.9% of the high-risk group (p = 0.004). The
      sensitivity for LA thrombus/SEC with a high CHADS(2) and CHA(2)DS(2)-VASc score
      was 64.8% and 88.7%, respectively (p = 0.0001). The specificity for LA
      thrombus/SEC with high CHADS(2) and CHA(2)DS(2)-VASc scores was 52.6% and 28.9%,
      respectively (p = 0.0001). In conclusion, both CHA(2)DS(2)-VASc and CHADS(2)
      scores are useful for stroke risk stratification in patients with atrial flutter.
      CHA(2)DS(2)-VASc had greater sensitivity for LA thrombus and SEC detection at the
      cost of reduced specificity.

PMID- 22133754
TI  - Comparison of outcomes in patients having isolated transcatheter aortic valve
      implantation versus combined with preprocedural percutaneous coronary
      intervention.
AB  - Coronary artery disease negatively affects the outcome of patients undergoing
      surgical aortic valve replacement and practice guidelines recommend
      revascularization at time of surgery. In patients undergoing transcatheter aortic
      valve implantation (TAVI), the impact of preprocedural percutaneous coronary
      intervention (PCI) on TAVI outcome has not been examined. We aimed in the present
      study to assess the feasibility and safety of performing PCI before TAVI and to
      evaluate procedural, 30-day, and 6-month clinical outcomes. We retrospectively
      analyzed 125 patients who underwent successful TAVI at a single institution and
      divided them into an isolated TAVI and a PCI + TAVI group. During the study
      period, a strategy of preprocedural PCI of all significant (>50%) lesions in
      major epicardial vessels was adopted. Study end points were adjudicated in
      accordance with the Valve Academic Research Consortium consensus on event
      definition. All patients were treated with the Medtronic CoreValve prosthesis (n
      = 55 with PCI + TAVI and n = 70 with isolated TAVI). Thirty-day mortality was 2%
      versus 6% for patients treated with PCI + TAVI versus isolated TAVI, respectively
      (p = 0.27). Neither periprocedural nor spontaneous myocardial infarction occurred
      in either group. Rates of 30-day stroke, major bleeding, major vascular
      complications, and the Valve Academic Research Consortium-defined combined safety
      end point (11% vs 13%, p = 0.74) did not differ between the 2 groups. Patients'
      symptoms significantly improved in the first month after TAVI, and extent of
      improvement did not differ between groups. Adverse events at 6 months were
      comparable. In conclusion, PCI before TAVI appears feasible and safe. Based on
      these early results revascularization should become an important consideration in
      patients with coronary artery disease undergoing TAVI.

PMID- 22133755
TI  - Development of postural control during gait in typically developing children: the
      effects of dual-task conditions.
AB  - The purpose of this study was to investigate the typical development of postural
      control in younger (5-6 yrs) and older (7-16 yrs) children (YTD and OTD) during
      two gait tasks, including level walking and obstacle-crossing, using a dual-task
      paradigm, and to compare the results of the children's performance with that of
      healthy young adults (HYA). Our findings revealed that gait control in typical
      children requires attentional resources to maintain stability. Moreover, dual
      task interference was less in HYA compared to YTD and OTD. Gait performance
      decrements in the dual-task context were greater in YTD compared to OTD, whereas
      cognitive performance decrements in YTD and OTD were similar. In addition, dual
      tasking affected cognitive performance more in YTD when gait task difficulty was
      increased. Results suggest a developmental trend in attentional resources used to
      control gait in typical children. Postural control during gait under dual-task
      conditions was improved when children were more mature, as attentional resources
      increased with age.

PMID- 22133756
TI  - A marginalized conditional linear model for longitudinal binary data when
      informative dropout occurs in continuous time.
AB  - Within the pattern-mixture modeling framework for informative dropout,
      conditional linear models (CLMs) are a useful approach to deal with dropout that
      can occur at any point in continuous time (not just at observation times).
      However, in contrast with selection models, inferences about marginal covariate
      effects in CLMs are not readily available if nonidentity links are used in the
      mean structures. In this article, we propose a CLM for long series of
      longitudinal binary data with marginal covariate effects directly specified. The
      association between the binary responses and the dropout time is taken into
      account by modeling the conditional mean of the binary response as well as the
      dependence between the binary responses given the dropout time. Specifically,
      parameters in both the conditional mean and dependence models are assumed to be
      linear or quadratic functions of the dropout time; and the continuous dropout
      time distribution is left completely unspecified. Inference is fully Bayesian. We
      illustrate the proposed model using data from a longitudinal study of depression
      in HIV-infected women, where the strategy of sensitivity analysis based on the
      extrapolation method is also demonstrated.

PMID- 22133757
TI  - Classification method for disease risk mapping based on discrete hidden Markov
      random fields.
AB  - Risk mapping in epidemiology enables areas with a low or high risk of disease
      contamination to be localized and provides a measure of risk differences between
      these regions. Risk mapping models for pooled data currently used by
      epidemiologists focus on the estimated risk for each geographical unit. They are
      based on a Poisson log-linear mixed model with a latent intrinsic continuous
      hidden Markov random field (HMRF) generally corresponding to a Gaussian
      autoregressive spatial smoothing. Risk classification, which is necessary to draw
      clearly delimited risk zones (in which protection measures may be applied),
      generally must be performed separately. We propose a method for direct classified
      risk mapping based on a Poisson log-linear mixed model with a latent discrete
      HMRF. The discrete hidden field (HF) corresponds to the assignment of each
      spatial unit to a risk class. The risk values attached to the classes are
      parameters and are estimated. When mapping risk using HMRFs, the conditional
      distribution of the observed field is modeled with a Poisson rather than a
      Gaussian distribution as in image segmentation. Moreover, abrupt changes in risk
      levels are rare in disease maps. The spatial hidden model should favor smoothed
      out risks, but conventional discrete Markov random fields (e.g. the Potts model)
      do not impose this. We therefore propose new potential functions for the HF that
      take into account class ordering. We use a Monte Carlo version of the expectation
      maximization algorithm to estimate parameters and determine risk classes. We
      illustrate the method's behavior on simulated and real data sets. Our method
      appears particularly well adapted to localize high-risk regions and estimate the
      corresponding risk levels.

PMID- 22133758
TI  - Evaluation of pulse cooximetry in patients undergoing abdominal or pelvic
      surgery.
AB  - BACKGROUND: Intraoperative transfusion decisions generally are guided by blood
      loss estimation and periodic invasive hemoglobin measurement. Continuous
      hemoglobin measurement by pulse cooximetry (pulse hemoglobin; Rainbow(r) SET
      Pulse CO-Oximeter, Masimo Corporation, Irvine, CA) has good agreement with
      laboratory hemoglobin in healthy volunteers and could aid transfusion decision
      making. Because intraoperative physiology may alter performance of this device,
      this study investigated pulse hemoglobin during surgery. METHODS: Ninety-one
      adult patients undergoing abdominal or pelvic surgery in which large blood loss
      was likely were studied. Time-matched pulse hemoglobin measurements were recorded
      for each intraoperative arterial hemoglobin measurement obtained. Agreement
      between measurements was assessed by average difference (mean +/- SD, g/dl),
      linear regression, and multiple measures Bland-Altman analysis. RESULTS: The
      average difference between 360 time-matched measurements (bias) was 0.50 +/- 1.44
      g/dl, with wider limits of agreement (-2.3 to 3.3 g/dl) than reported in healthy
      volunteers. The average difference between 269 paired sequential pulse and
      arterial hemoglobin changes was 0.10 +/- 1.11 g/dl, with half between -0.6 and
      0.7 g/dl of each other. The bias was larger in patients with blood loss of more
      than 1,000 ml; hemoglobin less than 9.0 g/dl; any intraoperative transfusion; or
      intraoperative decrease in arterial hemoglobin at the time of sampling >=2 g/dl
      (all P < 0.001). The range of bias was narrower at deeper anesthesia (P < 0.001).
      CONCLUSIONS: Evaluation of the sensor and software version tested suggests that
      although pulse cooximetry may perform well in ambulatory subjects, in patients
      undergoing surgery in which large blood loss is likely, an invasive measurement
      should be used in transfusion decision-making.

PMID- 22133759
TI  - Lidocaine metabolites inhibit glycine transporter 1: a novel mechanism for the
      analgesic action of systemic lidocaine?
AB  - BACKGROUND: Lidocaine exerts antinociceptive effects when applied systemically.
      The mechanisms are not fully understood but glycinergic mechanisms might be
      involved. The synaptic glycine concentration is controlled by glycine
      transporters. Whereas neurons express two types of glycine transporters,
      astrocytes specifically express glycine transporter 1 (GlyT1). This study focuses
      on effects of lidocaine and its major metabolites on GlyT1 function. METHODS: The
      effects of lidocaine and its metabolites monoethylglycinexylidide (MEGX),
      glycinexylidide, and N-ethylglycine on GlyT1 function were investigated in uptake
      experiments with [14C]-labeled glycine in primary rat astrocytes. Furthermore,
      the effect of lidocaine and its metabolites on glycine-induced currents were
      investigated in GlyT1-expressing Xenopus laevis oocytes. RESULTS: Lidocaine
      reduced glycine uptake only at toxic concentrations. The metabolites MEGX,
      glycinexylidide, and N-ethylglycine, however, significantly reduced glycine
      uptake (P < 0.05). Inhibition of glycine uptake by a combination of lidocaine
      with its metabolites at a clinically relevant concentration was diminished with
      increasing extracellular glycine concentrations. Detailed analysis revealed that
      MEGX inhibits GlyT1 function (P < 0.05), whereas N-ethylglycine was identified as
      an alternative GlyT1 substrate (EC50 = 55 MUM). CONCLUSIONS: Although lidocaine
      does not function directly on GlyT1, its metabolites MEGX and N-ethylglycine
      [corrected] were shown to inhibit GlyT1-mediated glycine uptake by at least two
      different mechanisms. Whereas N-ethylglycine [corrected] was demonstrated to be
      an alternative GlyT1 substrate, MEGX was shown to inhibit GlyT1 activity in both
      primary astrocytes and in GlyT1-expressing Xenopuslaevis oocytes at clinically
      relevant concentrations. These findings provide new insights into the possible
      mechanisms for the antinociceptive effect of systemic lidocaine.

PMID- 22133760
TI  - The 24-bp consensus sequence responsible for regulation of the BphS1T1 two
      component system in a hybrid promoter.
AB  - Rhodococcus jostii RHA1 degrades polychlorinated biphenyls (PCBs) by cometabolism
      with biphenyl. The bphS1T1-coding two-component system, which is composed of a
      sensor kinase, BphS1, and a response regulator, BphT1, activates the
      transcription of biphenyl/PCB degradation genes from the five promoters of bphAa,
      etbAa1, etbAa2, etbAd, and etbD1 in the presence of aromatics, such as biphenyl
      and ethylbenzene. The transcription start sites of etbAd and etbD1 were
      determined and the results indicated that the 18-bp consensus sequence is shared
      by all five promoters at the equivalent position from their transcriptional start
      sites. To investigate the involvement of the 18-bp consensus sequence in the
      regulation of BphS1T1, a hybrid promoter was constructed by connecting the 18-bp
      consensus sequence of bphAa promoter to a portion of the benzoate dioxygenase
      gene promoter, which is not under the control of BphS1T1. The ethylbenzene
      dependent induction of the hybrid promoter by BphS1T1 was not observed. Recently,
      a 24-bp consensus sequence that included the 18-bp consensus sequence of the
      bphAa promoter was identified in the regions conserved among RHA1 and other
      rhodococcal degraders. When the 24-bp consensus sequence was employed instead,
      both BphS1T1-dependent basal activation and ethylbenzene-dependent induction of
      the hybrid promoter were observed. Mutations in the six extra residues outside
      the 18-bp sequence in the 24-bp consensus sequence, affected not only
      ethylbenzene-dependent induction but also BphS1T1-dependent basal activation. The
      outstanding conservation of the 24-bp consensus sequence was confirmed by
      multiple sequence alignment. These results indicate that the 24-bp consensus
      sequence is really responsible for the regulation of BphS1T1.

PMID- 22133761
TI  - Metabolic syndrome, diabetes, poor cognition, and dementia in the Caerphilly
      prospective study.
AB  - We have examined whether metabolic syndrome is associated with intermediate risk
      of impaired cognition between people with and without diabetes. Men aged 45 to 59
      years were identified from Caerphilly in South Wales, United Kingdom.
      Participation rate was 89% (41% of the original cohort) and 2,512 men were
      examined in phase one from July 1979 until September 1983. Follow-up examinations
      occurred at four intervals until 2004 when 1,225 men participated. Participants
      were categorized on the basis of their exposure to metabolic syndrome not
      diabetes (MSND) and diabetes (with or without metabolic syndrome) at each of the
      first three phases. Neuropsychological outcomes and clinical diagnosis of
      cognitive impairment not dementia (CIND) and dementia were assessed at phase
      five. The prevalence of MSND increased from 1% to 5% and for diabetes from 3% to
      9% between phase one and phase three. 15% of participants had CIND and 8%
      dementia. People with diabetes, but not those with MSND, at phases one, two, or
      three had poorer cognition at phase five (adjusted beta coefficient AH4 -4.3 95%
      CI -7.9, -0.7; phase two: -2.5 95% CI -4.7, -0.3; phase three: -2.3 95% CI -4.2, 
      0.5). The adjusted odds ratio (phase one) for diabetes and CIND was 4.0 (95% CI
      1.4, 11.5) and dementia 0.61 (95% CI 0.07, 5.37). After adjustment, higher
      systolic blood pressure was the only component of the metabolic syndrome
      associated with worse cognitive outcomes. Diabetes in mid-life, but not MSND, is
      associated with impaired cognition and increased odds of CIND in later life.

PMID- 22133763
TI  - An innovative joint approach to HIV and lymphoma care.

PMID- 22133762
TI  - Overexpression of amyloid-beta protein precursor induces mitochondrial oxidative
      stress and activates the intrinsic apoptotic cascade.
AB  - Aberrant processing of amyloid-beta protein precursor (AbetaPP) into amyloid-beta
      (Abeta) fragments underlies the formation of senile plaques in Alzheimer's
      disease (AD). Moreover, Abeta fragments, particularly Abeta(42), exert direct
      toxic effects within neurons including the induction of mitochondrial oxidative
      stress (MOS). Interestingly, individuals with Down syndrome (DS) frequently
      develop early onset AD as a major co-morbid phenotype. One hypothesis for AD
      associated with DS involves the overexpression of wild type (WT) AbetaPP protein,
      due to its location on chromosome 21. However, the mechanism by which the
      overexpression of WT AbetaPP might trigger MOS and induce cell death is presently
      unclear. Here we show that transient overexpression of DsRed2-tagged AbetaPP (WT)
      in CHO cells induces caspase-3 activation and nuclear fragmentation indicative of
      apoptosis. AbetaPP localizes to the mitochondrial fraction of transfected CHO
      cells and induces glutathione-sensitive opening of the mitochondrial permeability
      transition pore (mPTP) and cytochrome c release. MOS and intrinsic apoptosis
      induced by AbetaPP are significantly inhibited by co-expression of Bcl-2 or
      treatment with either glutathione or a pan-caspase inhibitor. The mPTP inhibitor,
      cyclosporin A, also significantly attenuates AbetaPP-induced apoptosis. AbetaPP
      induced apoptosis is unaffected by a beta-secretase inhibitor and is independent
      of detectable Abeta(42); however, a gamma-secretase inhibitor significantly
      protects against AbetaPP overexpression, suggesting a possible role of the
      AbetaPP intracellular domain in cell death. These data indicate that
      overexpression of WT AbetaPP is sufficient to induce MOS and intrinsic apoptosis,
      suggesting a novel pro-oxidant role for AbetaPP at mitochondria which may be
      relevant in AD and DS disease pathologies.

PMID- 22133764
TI  - Endothelial dysfunction of the peripheral vascular bed in the acute phase after
      ischemic stroke.
AB  - BACKGROUND: Endothelial dysfunction (ED) is relevant for the development of
      cerebrovascular and cardiovascular diseases. Asymmetric dimethylarginine (ADMA)
      competes with L-arginine and has been implicated in the development of ED.
      Increased levels of ADMA have been found in chronic heart failure (CHF). We
      hypothesized that peripheral ED in acute ischemic stroke is associated with
      increased ADMA levels. METHODS: We evaluated 60 patients with acute stroke in the
      territory of the middle cerebral artery. Stroke patients were classified
      according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST)
      classification. We compared these patients with patients of similar age without
      known cardiovascular disease (negative controls, n = 23) and patients with
      stable, ambulatorily treated CHF (n = 46, left ventricular ejection fraction =
      33.8 +/- 10.9) with known ED (positive controls). Peripheral endothelial function
      was assessed by EndoPAT2000 technology using the reactive hyperemia index (RHI).
      RESULTS: RHI was significantly decreased in stroke and in CHF compared to
      controls (1.8 +/- 0.3 vs. 1.8 +/- 0.4 vs. 2.2 +/- 0.4, respectively, ANOVA p =
      0.01). A decreased RHI was observed in cardioembolic and lacunar infarcts and
      stroke of undetermined etiology (1.7 +/- 0.4, 1.8 +/- 0.5 and 1.7 +/- 0.3, p <
      0.0001). The L-arginine/ADMA ratio was significantly decreased in stroke and in
      CHF (147.6 +/- 31.7 and 126.1 +/- 37.9 vs. controls: 161.5 +/- 26.1, p < 0.0001)
      and was lowest in stroke patients in the cardioembolic group (133.0 +/- 29.4, p <
      0.0001). A lower L-arginine/ADMA ratio was associated with ED in cardioembolic
      stroke and CHF (r = 0.324, p < 0.05 and r = 0.429, p < 0.0001). CONCLUSION:
      Peripheral ED occurs to a similar degree in acute ischemic stroke and CHF. The
      impaired vasodilator capacity of peripheral arteries reflects the TOAST
      classification. ADMA may play a role in ED in both acute ischemic stroke and CHF.

PMID- 22133765
TI  - Multiple sclerosis: is prevalence rising and if so why?

PMID- 22133766
TI  - Semiautomated segmentation of the human spine based on echoplanar images.
AB  - The number of functional magnetic resonance imaging (fMRI) studies performed on
      the human spinal cord (SC) has considerably increased in recent years. The lack
      of a validated processing pipeline is, however, a significant obstacle to the
      spread of SC fMRI. One component likely to be involved in any such pipeline is
      the process of SC masking, analogous to brain extraction in cerebral fMRI. In
      general, SC masking has been performed manually, with the incumbent costs of
      being very time consuming and operator dependent. To overcome these drawbacks, we
      have developed a tailored semiautomatic method for segmenting echoplanar images
      (EPI) of human spine that is able to identify the spinal canal and the SC. The
      method exploits both temporal and spatial features of the EPI series and was
      tested and optimized on EPI images of cervical spine acquired at 3 T. The
      dependence of algorithm performance on the degree of EPI image distortion was
      assessed by computing the displacement warping field that best matched the EPI to
      the corresponding high-resolution T(2) images. Segmentation accuracy was above
      80%, a significant improvement over values obtained with similar approaches, but
      not exploiting temporal information. Geometric distortion was found to explain
      about 50% of the variance of algorithm classification efficiency.

PMID- 22133767
TI  - Abnormal telomere shortening of peripheral blood mononuclear cells and
      granulocytes in patients with chronic idiopathic neutropenia.
AB  - BACKGROUND: Chronic idiopathic neutropenia is characterized by immune-mediated
      suppression of neutrophil production. Because patients with immune-mediated bone
      marrow failure syndromes display age-inappropriate telomere shortening in
      leukocytes, we investigated telomere lengths in peripheral blood mononuclear
      cells and granulocytes of patients with chronic idiopathic neutropenia. DESIGN
      AND METHODS: We studied 37 patients with chronic idiopathic neutropenia and 68
      age- and sex-matched healthy controls. Relative telomere length and telomerase
      reverse transcriptase expression were assessed by a quantitative real time
      polymerase chain reaction. Telomerase activity was determined by a polymerase
      chain reaction-based immunoassay. RESULTS: The mean relative telomere values of
      peripheral blood mononuclear cells and granulocytes were significantly lower in
      patients compared to controls, and significantly lower than expected on the basis
      of the age-adjusted healthy control distribution. The difference in the relative
      telomere lengths between patients and controls in both peripheral blood
      mononuclear cells and granulocytes was prominent in those under the age of 50
      years. Contrary to the peripheral blood mononuclear cells, in which an inverse
      correlation was observed between relative telomere values and age, no significant
      correlation was noted between granulocyte telomere values and patient age. A
      significant correlation was observed between individual relative telomere values
      and absolute neutrophil counts. There was no difference in expression of
      telomerase reverse transcriptase in peripheral blood mononuclear cells between
      patients and controls but telomerase activity was identified at a significantly
      higher frequency in controls than in patients. No correlation was found between
      telomerase activity or telomerase reverse transcriptase expression and relative
      telomere lengths of peripheral blood mononuclear cells. CONCLUSIONS: Patients
      with chronic idiopathic neutropenia display age-inappropriate telomere shortening
      of peripheral blood cells and low telomerase activity in peripheral blood
      mononuclear cells. A compensatory increased proliferation of bone marrow
      hematopoietic progenitor cells in association with lymphocyte replicative
      exhaustion probably account for these abnormalities.

PMID- 22133768
TI  - Risk factors for in-hospital venous thromboembolism in children: a case-control
      study employing diagnostic validation.
AB  - BACKGROUND: Studies evaluating risk factors for in-hospital venous
      thromboembolism in children are limited by quality assurance of case definition
      and/or lack of controlled comparison. The objective of this study is to determine
      risk factors for the development of in-hospital venous thromboembolism in
      children. DESIGN AND METHODS: In a case-control study at The Children's Hospital,
      Colorado, from 1(st) January 2003 to 31(st) December 2009 we employed diagnostic
      validation methods to determine pediatric in-hospital venous thromboembolism risk
      factors. Clinical data on putative risk factors were retrospectively collected
      from medical records of children with International Classification of Diseases,
      9th edition codes of venous thromboembolism at discharge, in whom radiological
      reports confirmed venous thromboembolism and no signs/symptoms of venous
      thromboembolism were noted on admission. RESULTS: We verified 78 cases of in
      hospital venous thromboembolism, yielding an average incidence of 5 per 10,000
      hospitalized children per year. Logistical regression analyses revealed that
      mechanical ventilation, systemic infection, and hospitalization duration of five
      days or over were statistically significant, independent risk factors for in
      hospital venous thromboembolism (OR=3.29, 95%CI=1.53-7.06, P=0.002; OR=3.05,
      95%CI=1.57-5.94, P=0.001; and OR=1.03, 95%CI=1.01-1.04, P=0.001, respectively).
      Using these factors in a risk model, post-test probability of venous
      thromboembolism was 3.6%. CONCLUSIONS: These data indicate that risk of in
      hospital venous thromboembolism in children with this risk factor combination may
      exceed that of hospitalized adults in whom prophylactic anticoagulation is
      indicated. Substantiation of these findings via multicenter studies could provide
      the basis for future risk-stratified randomized control trials of pediatric
      venous thromboembolism prevention.

PMID- 22133769
TI  - Detection of BRAF mutations in patients with hairy cell leukemia and related
      lymphoproliferative disorders.
AB  - Hairy cell leukemia has been shown to be strongly associated with the BRAF V600E
      mutation. We screened 59 unenriched archived bone marrow aspirate and peripheral
      blood samples from 51 patients with hairy cell leukemia using high resolution
      melting analysis and confirmatory Sanger sequencing. The BRAF V600E mutation was
      detected in 38 samples (from 36 patients). The BRAF V600E mutation was detected
      in all samples with disease involvement above the limit of sensitivity of the
      techniques used. Thirty-three of 34 samples from other hematologic malignancies
      were negative for BRAF mutations. A BRAF K601E mutation was detected in a patient
      with splenic marginal zone lymphoma. Our data support the recent finding of a
      disease defining point mutation in hairy cell leukemia. Furthermore, high
      resolution melting with confirmatory Sanger sequencing are useful methods that
      can be employed in routine diagnostic laboratories to detect BRAF mutations in
      patients with hairy cell leukemia and related lymphoproliferative disorders.

PMID- 22133770
TI  - Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination
      therapy for steroid-resistant chronic graft-versus-host disease.
AB  - BACKGROUND: Chronic graft-versus-host disease is a common late complication of
      allogeneic hematopoietic stem cell transplantation. Corticosteroids are the
      standard initial treatment. Second-line treatment has not been well defined. We
      evaluated the effectiveness and safety of low doses of alemtuzumab plus low doses
      of rituximab in the treatment of steroid-refractory chronic graft-versus-host
      disease. DESIGN AND METHODS: Ten men and 5 women were prospectively included in
      the study. All patients received one cycle of subcutaneous alemtuzumab 10
      mg/day/3 days and intravenous rituximab 100 mg on Days +4, +11, +18 and +25. The
      therapeutic response was measured on Days +30, +90 and +365 of the protocol.
      RESULTS: Median age was 41 years. The main site involved was the oral mucosa
      (86.7%) followed by the eyes (66.7%), liver (60%), skin (53%), lungs (13.3%) and
      intestinal tract (6.7%). The overall response was 100% at Day +30 evaluation: 10
      patients (67%) had partial remission, 5 (33%) had complete remission. At Day +90
      evaluation, 7 (50%) patients had partial remission, 4 (28%) had complete
      remission; 3 (21%) had relapsed chronic graft-versus-host disease and one patient
      did not reach the evaluation time point. So far, 5 patients have reached the Day
      +365 follow-up evaluation; 2 (40%) had partial remission, 2 had complete
      remission and one experienced chronic graft-versus-host disease progression.
      Adverse effects were mainly infections in 67% of patients; these were all quickly
      solved, except for one patient who died from pneumonia. CONCLUSIONS: This
      combination therapy appears to be an efficacious and safe treatment for steroid
      refractory chronic graft-versus-host disease. Longer follow up to determine the
      durability of response and survival is required (ClinicalTrials.gov:
      NCT01042509).

PMID- 22133771
TI  - Phase II trial of vorinostat and gemtuzumab ozogamicin as induction and post
      remission therapy in older adults with previously untreated acute myeloid
      leukemia.
AB  - Histone deacetylase inhibitors such as vorinostat enhance gemtuzumab ozogamicin
      efficacy in vitro. We, therefore, investigated vorinostat+gemtuzumab ozogamicin
      for adults aged 60 years and over with untreated acute myeloid leukemia. We
      stratified patients into 2 groups (group 1: patients aged >= 70 years and
      performance status 2-3; group 2: aged 60-69 years with performance status 0-3 or
      aged >= 70 years and performance status 0-1). Responses were monitored separately
      in group 2 patients with normal or favorable cytogenetics (group 2A) and other
      cytogenetics (group 2B). Among 31 patients, 6 (19.4%) achieved complete
      remission, and one (3.2%) achieved complete remission with incomplete platelet
      recovery; these patients had a higher median overall survival than non-responders
      (553 vs. 131 days, P = 0.0026). Response rates were: group 1, one of 10 (10.0%);
      group 2A, 6 of 13 (46.2%); and group 2B, none of 8 (0%). These data indicate that
      vorinostat+gemtuzumab ozogamicin has activity that is mostly confined to patients
      with normal karyotype disease. ClinicalTrial.gov: NCT00673153.

PMID- 22133772
TI  - A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in
      untreated diffuse large B-cell lymphoma with analysis of outcome by molecular
      subtype.
AB  - BACKGROUND: A phase II trial of dose-adjusted etoposide, prednisone, vincristine,
      cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) from the National Cancer
      Institute showed promising activity in untreated diffuse large B-cell lymphoma.
      The Cancer and Leukemia Group B conducted a study to determine if these results
      could be reproduced in a multi-institutional setting. DESIGN AND METHODS: The
      study included 69 patients with untreated diffuse large B-cell lymphoma at least
      18 years of age and at least stage II. Radiaton therapy was not permitted on
      study. Median age was 58 years (range 23-83) and 40% had high-intermediate or
      high International Prognostic Index risk. Immunohistochemical biomarkers for cell
      of origin and proliferation were performed. RESULTS: With a median follow up of
      62 months, time to progression and overall survival were 81% and 84%,
      respectively, and time to progression was 87%, 92% and 54% for low/low
      intermediate, high-intermediate and high International Prognostic Index risk
      groups, respectively, at 5-years and beyond. The time to progression and event
      free survival of germinal center B-cell lymphoma were 100% and 94%, respectively,
      and non-germinal center B-cell GCB diffuse large B-cell lymphoma were 67% and
      58%, respectively, at 62 months (germinal center vs. non-germinal center B cell
      P=0.008). DA-EPOCH-R was tolerated without significant grade 4 non-hematologic
      toxicities. CONCLUSIONS: These results provide the first confirmation by a multi
      institutional group that DA-EPOCH-R provides high durable remissions in diffuse
      large B-cell lymphoma and is effective in both germinal center and non-germinal
      center B-cell subtypes. The trial was registered at ClinicalTrials.Gov
      (NCT00032019).

PMID- 22133774
TI  - Platelet adhesion to decorin but not collagen I correlates with the integrin
      alpha2 dimorphism E534K, the basis of the human platelet alloantigen (HPA)-5
      system.
AB  - A single nucleotide polymorphism in the integrin alpha2 gene ITGA2 (rs1801106;
      G1600A) creates the non-conservative amino acid substitution E534K, the basis of
      the human platelet alloantigen system HPA-5. Yet HPA-5 alleles do not influence
      binding of alpha2beta1 to its primary ligand collagen I, and the effect of HPA-5
      on platelet function has not been determined. We used a direct platelet adhesion
      assay to evaluate whether differential inheritance of HPA-5 alleles influences
      platelet adhesion to collagen I or an alternative ligand, decorin. Platelets from
      donors bearing one or more minor allele HPA-5b showed attenuated adhesion to
      purified decorin but not collagen I. Adhesion to decorin was significantly
      inhibited by human alloantibodies specific for HPA-5a but not by the collagen I
      sequence GFOGER or alpha2-specific inhibitory monoclonal antibodies. The minor
      allele 534K attenuates platelet adhesion to decorin but not collagen I, providing
      the first evidence of a functional effect of HPA-5 alleles.

PMID- 22133773
TI  - Systematic review of purine analog treatment for chronic lymphocytic leukemia:
      lessons for future trials.
AB  - A systematic review of purine analogs revealed heterogeneity between trials in
      treatment effects on response and progression free survival, but not survival,
      perhaps partly due to variations in analytical methods. In addition, combination
      treatments required evaluation. Therefore, individual patient data were sought
      for all randomized trials in untreated chronic lymphocytic leukemia which
      involved a purine analog, but which did not include antibody therapies. Sixteen
      trials were found, addressing seven comparisons. Eight trials, with 2,753
      patients, showed that single agent purine analog improved progression free
      survival (odds ratio=0.71; 95% confidence interval=0.63-0.79). Heterogeneity
      remained substantial. Three trials, with 1,403 patients, showed that progression
      free survival was further improved by the addition of cyclophosphamide (odds
      ratio=0.54; 0.47-0.62). Fewer data were available on the addition of other drugs
      to purine analog, and none showed clear benefit. Two trials, with 544 patients,
      suggested cladribine improved progression free survival compared to fludarabine
      (odds ratio=0.77; 0.63-0.95). No differences were seen in overall survival for
      any comparisons. In conclusion, purine analogs, particularly combined with
      cyclophosphamide, significantly improve progression free survival but not
      survival. Some groups, such as the elderly, may not see the same benefits and
      maximizing doses may be important for all treatments, including chlorambucil.
      Longer follow up, consistent definitions and detailed reporting of trials should
      be encouraged.

PMID- 22133775
TI  - Tyrosine phosphorylation of WASP promotes calpain-mediated podosome disassembly.
AB  - Podosomes are actin-based adhesions involved in migration of cells that have to
      cross tissue boundaries such as myeloid cells. The Wiskott Aldrich Syndrome
      Protein regulates de novo actin polymerization during podosome formation and it
      is cleaved by the protease calpain during podosome disassembly. The mechanisms
      that may induce the Wiskott Aldrich Syndrome Protein cleavage by calpain remain
      undetermined. We now report that in myeloid cells, tyrosine phosphorylation of
      the Wiskott Aldrich Syndrome Protein-tyrosine291 (Human)/tyrosine293 (mouse) not
      only enhances Wiskott Aldrich Syndrome Protein-mediated actin polymerization but
      also promotes its calpain-dependent degradation during podosome disassembly. We
      also show that activation of the Wiskott Aldrich Syndrome Protein leading to
      podosome formation occurs independently of tyrosine phosphorylation in spleen
      derived dendritic cells. We conclude that tyrosine phosphorylation of the Wiskott
      Aldrich Syndrome Protein integrates dynamics of actin and cell adhesion proteins
      during podosome disassembly required for mobilization of myeloid cells during the
      immune response.

PMID- 22133777
TI  - Efficacy of combining dasatinib and FLAG-IDA for patients with chronic myeloid
      leukemia in blastic transformation.

PMID- 22133776
TI  - Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory
      multiple myeloma: results from OPTIMUM, a randomized trial.
AB  - BACKGROUND: Thalidomide has potent antimyeloma activity, but no prospective,
      randomized controlled trial has evaluated thalidomide monotherapy in patients
      with relapsed/refractory multiple myeloma. DESIGN AND METHODS: We conducted an
      international, randomized, open-label, four-arm, phase III trial to compare three
      different doses of thalidomide (100, 200, or 400 mg/day) with standard
      dexamethasone in patients who had received one to three prior therapies. The
      primary end-point was time to progression. RESULTS: In the intent-to-treat
      population (N=499), the median time to progression was 6.1, 7.0, 7.6, and 9.1
      months in patients treated with dexamethasone, and thalidomide 100, 200, and 400
      mg/day, respectively; the difference between treatment groups was not
      statistically significant. In the per-protocol population (n=465), the median
      time to progression was 6.0, 7.0, 8.0, and 9.1 months, respectively. In patients
      who had received two or three prior therapies, thalidomide significantly
      prolonged the time to progression at all dose levels compared to the result
      achieved with dexamethasone. Response rates and median survival were similar in
      all treatment groups, but the median duration of response was significantly
      longer in all thalidomide groups than in the dexamethasone group. Adverse events
      reported in the thalidomide groups, such as fatigue, constipation and neuropathy,
      confirmed the known safety profile of thalidomide. CONCLUSIONS: Although
      thalidomide was not superior to dexamethasone in this randomized trial,
      thalidomide monotherapy may be considered an effective salvage therapy option for
      patients with relapsed/refractory multiple myeloma, particularly those with a
      good prognosis and those who have received two or three prior therapies. The
      recommended starting dose of thalidomide monotherapy is 400 mg/day, which can be
      rapidly reduced for patients who do not tolerate this treatment. ( CLINICAL TRIAL
      REGISTRATION NUMBER: NCT00452569).

PMID- 22133778
TI  - Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative
      allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation is associated with
      profound changes in levels of various cytokines. Emphasis has been placed on
      conditioning-associated mucosal damage and neutropenia and associated bacterial
      translocation as the initiating conditions predisposing to acute graft-versus
      host disease. The post-transplant period is, however, also associated with
      increases in certain homeostatic cytokines. It is unclear how much the
      homeostatic drive to lymphocyte recovery and the production of cytokines from the
      engrafting donor immune system determine cytokine fluctuations in the peri- and
      immediate post-transplant period. The aim of this study was to examine the
      contributions of the conditioning regimen, donor engraftment, infections, and
      graft-versus-host disease to fluctuations in cytokines involved in homeostasis
      and inflammation. DESIGN AND METHODS: We examined the levels of 33 cytokines in
      relation to peri- and post-transplant events such as conditioning regimen,
      chimerism, and acute graft-versus-host disease in myeloablative, non-T cell
      replete HLA-identical sibling donor stem cell transplantation for hematologic
      malignancies. RESULTS: We identified two cytokine storms. The first occurred
      following conditioning and reached peak levels when all the leukocytes were at
      their lowest concentrations. The second cytokine storm occurred concurrently with
      hematopoietic reconstitution and subsided with the achievement of full donor
      lymphocyte chimerism. CONCLUSIONS: Our results indicate that both recipient
      related and donor-related factors contribute to the changes in cytokine levels in
      the recipient following allogeneic hematopoietic stem cell transplantation. The
      study reported here was performed using plasma samples drawn from patients
      enrolled in the ClinicalTrials.gov-registered trials NCT00467961 and NCT00378534.

PMID- 22133779
TI  - Overexpression of SET is a recurrent event associated with poor outcome and
      contributes to protein phosphatase 2A inhibition in acute myeloid leukemia.
AB  - BACKGROUND: Protein phosphatase 2A is a novel potential therapeutic target in
      several types of chronic and acute leukemia, and its inhibition is a common event
      in acute myeloid leukemia. Upregulation of SET is essential to inhibit protein
      phosphatase 2A in chronic myeloid leukemia, but its importance in acute myeloid
      leukemia has not yet been explored. DESIGN AND METHODS: We quantified SET
      expression by real time reverse transcriptase polymerase chain reaction in 214
      acute myeloid leukemia patients at diagnosis. Western blot was performed in acute
      myeloid leukemia cell lines and in 16 patients' samples. We studied the effect of
      SET using cell viability assays. Bioinformatics analysis of the SET promoter,
      chromatin immunoprecipitation, and luciferase assays were performed to evaluate
      the transcriptional regulation of SET. RESULTS: SET overexpression was found in
      60/214 patients, for a prevalence of 28%. Patients with SET overexpression had
      worse overall survival (P<0.01) and event-free survival (P<0.01). Deregulation of
      SET was confirmed by western blot in both cell lines and patients' samples.
      Functional analysis showed that SET promotes proliferation, and restores cell
      viability after protein phosphatase 2A overexpression. We identified EVI1
      overexpression as a mechanism involved in SET deregulation in acute myeloid
      leukemia cells. CONCLUSIONS: These findings suggest that SET overexpression is a
      key mechanism in the inhibition of PP2A in acute myeloid leukemia, and that EVI1
      overexpression contributes to the deregulation of SET. Furthermore, SET
      overexpression is associated with a poor outcome in acute myeloid leukemia, and
      it can be used to identify a subgroup of patients who could benefit from future
      treatments based on PP2A activators.

PMID- 22133780
TI  - Thrombolytic therapy is effective in paroxysmal nocturnal hemoglobinuria: a
      series of nine patients and a review of the literature.
AB  - BACKGROUND: Thrombosis is the major risk factor for death in patients with
      paroxysmal nocturnal hemoglobinuria. Previous case reports indicate that venous
      thrombosis in patients with paroxysmal nocturnal hemoglobinuria is amenable to
      thrombolysis. DESIGN AND METHODS: We reviewed the outcome of thrombolytic therapy
      for patients with paroxysmal nocturnal hemoglobinuria who had thromboses
      refractory to anticoagulation at our institutions. RESULTS: In this study of 41
      patients who had at least one thrombotic event, we confirmed a very high
      incidence of recurrence despite anticoagulation. Nine patients with thrombosis
      were regarded as eligible for administration of intravenous tissue plasminogen
      activator, which was effective in reversing thrombi in all of 15 occasions in
      which it was given. Serious hemorrhagic complications developed in three cases.
      At last follow-up visit, of the nine patients treated, three had died, and six
      were in very good to excellent condition in terms of clinical outcome and
      radiological findings. The only patient in whom thrombolysis may have contributed
      to a fatal outcome also had complications of "heparin induced thrombocytopenia
      with thrombosis", which we diagnosed in three additional patients. In our review
      of the literature, nine out of 15 patients treated with thrombolysis have had a
      good outcome. CONCLUSIONS: Although it is associated with a significant but
      manageable risk of bleeding, systemic thrombolysis is a highly effective
      treatment for reversing venous thromboses in patients with paroxysmal nocturnal
      hemoglobinuria.

PMID- 22133781
TI  - A novel assay for the detection of anti-human platelet antigen antibodies (HPA
      1a) based on peptide aptamer technology.
AB  - BACKGROUND: Neonatal alloimmune thrombocytopenia is mostly due to the presence of
      maternal antibodies against the fetal platelet antigen HPA-1a on the platelet
      integrin GPIIb-IIIa. Accurate detection of anti-HPA-1a antibodies in the mother
      is, therefore, critical. Current diagnostic assays rely on the availability of
      pools of human platelets that vary according to donors and blood centers. There
      is still no satisfactory standardization of these assays. DESIGN AND METHODS:
      Peptide aptamer was used to detect and identify HPA-1a-specific antibodies in
      human serum that do not require human platelets. A peptide aptamer library was
      screened using an anti-HPA-1a human monoclonal antibody as a bait to isolate an
      aptamer that mimics the human platelet antigen HPA-1a. RESULTS: This is the first
      report in platelet immunology of the use of a peptide aptamer for diagnostic
      purposes. This assay gives better results than the MAIPA currently in use,
      detecting around 90% of the expected alloantibodies. CONCLUSIONS: This assay
      could help define a standard for the quantitation of anti-HPA antibodies. This
      report also demonstrates that peptide aptamers can potentially detect a variety
      of biomarkers in body fluids; this is of particular interest for diagnostic
      purposes.

PMID- 22133782
TI  - Standardization non-invasive fetal RHD and SRY determination into clinical
      routine using a new multiplex RT-PCR assay for fetal cell-free DNA in pregnant
      women plasma: results in clinical benefits and cost saving.
AB  - INTRODUCTION: Among negative RhD mothers it is essential to know the fetal RhD
      status in order to avoid the possibility of hemolytic disease of the newborn. In
      this regard, the detection of fetal DNA in maternal plasma might become a new
      diagnostic tool. In the current study, we have evaluated the standardization of a
      Multiplex-PCR targeted towards two exons of the RHD and one SRY gene to monitor
      RhD negative women. The current study addresses questions concerning feasibility
      and applicability of this approach into the clinical practice. MATERIALS AND
      METHODS: Both single and multiplex real-time PCRs targeting RHD exons 5 and 7 and
      SRY were applied for the detection of fetal-specific RHD sequences and sex in
      maternal plasma. A large cohort of 2127 women was studied between 10 and 28 weeks
      of pregnancy. 134 of them were used for single TaqMan PCR studies and 1993 were
      evaluated using Multiplex TaqMan PCR studies. All of them were serologically
      typed as RhD negative according to Spanish guidelines. Single and multiplex real
      time PCR results were compared with postnatal serology and sex identification.
      RESULTS: There was a 100% concordance between results obtained with single and
      multiplex real-time PCR assays. At present, 1012 of the 1993 pregnant women
      studied gave birth and the results of RHD status obtained with the multiplex
      TaqMan PCR assay were confirmed postpartum by serological methods showing that
      sensitivity, specificity, and accuracy of the multiplex assay were 100, 98.6, and
      99.3%, respectively. This procedure improved the speed of the assay, avoided over
      treatment among RhD negative pregnant women bearing RhD negative fetus, and
      reduced the requirements for clinical and biological monitoring, resulting in a
      clinical benefit and cost saving. CONCLUSIONS: The routine determination of fetal
      RHD status and SRY in maternal plasma, using multiplex real-time PCR, is
      feasible. The use of multiplex real-time PCR allows improving the response of the
      laboratory, saving time and reagent costs, opening the door to a complete
      automatization of the process.

PMID- 22133783
TI  - The relationship between insulin-like growth factor-1 and metabolic syndrome,
      independent of adiponectin.
AB  - BACKGROUND: Insulin-like growth factor-1 (IGF-1) is associated with obesity and
      aging, and was recently linked to metabolic syndrome (MetS) and insulin
      resistance. However, little is known about the relationship between IGF-1 and
      adiponectin (adiponectin), another marker of MetS. METHODS: We measured the
      plasma IGF-1 and adiponectin levels of 3099 subjects (1869 males, 55.9+/-10.8 y).
      We applied the Korean-modified International Diabetes Foundation (k-IDF) criteria
      for determination of, and risk assessment for, MetS. RESULTS: K-IDF criteria
      based MetS occurred in 37.0% (n=1146) of patients. IGF-1 (91.5 vs. 97.3 ng/ml,
      p<0.001) and adiponectin (3.95 vs. 4.23 MUg/ml, p<0.001) were significantly lower
      in MetS patients than without MetS. Lower IGF-1 was associated with increasing
      numbers of MetS abnormalities, independent of adiponectin (p for trend<0.001,
      F=12.615, p<0.001 in ANCOVA). MetS prevalence in individuals with both high IGF-1
      and adiponectin levels (6.7%, n=206) was significantly lower than in other
      groups. Both high IGF-1 and adiponectin group was associated with reduced MetS
      risk after adjusting for other confounding factors (OR 0.694, 95% CI 0.493-0.977,
      p=0.036). CONCLUSIONS: IGF-1 was associated with MetS independent of adiponectin
      in our study. The independent relationship between IGF-1 and MetS provides
      insight into the pathophysiologic mechanisms of MetS.

PMID- 22133784
TI  - Long-term mortality and hospital readmission after acute myocardial infarction:
      an eight-year follow-up study.
AB  - INTRODUCTION AND OBJECTIVES: Acute myocardial infarction is responsible for most
      of the deaths in developed countries and for a very large number of hospital
      admissions. Specifically in Spain, each year about 140,000 deaths and 5 million
      hospital stays are due to acute myocardial infarction, corresponding to health
      care costs reaching 15% of total expenditure. Therefore, this paper presents an
      exhaustive analysis of acute myocardial infarction and the related prognosis,
      such as recurrence and mortality. METHODS: This observational study was carried
      out in Spain. Data were obtained using the Hospital Discharge Administrative
      Database from 2000 through 2007, inclusive. Specifically, 12,096 cases of acute
      myocardial infarction (8606 women and 3490 men) were reported during this period,
      with 2395 readmissions for this diagnosis. Readmissions were analyzed for
      frequency and duration using logistic regression and the Wang survival model.
      Mortality was analyzed using logistic regression. RESULTS: Readmission rates were
      50% for patients younger than 45 years and 38% for those older than 75 years
      (P<.001). Men were readmitted more frequently than women throughout the follow-up
      period. Variables related to hospital mortality from acute myocardial infarction
      were the presence of diabetes, previous ischemic heart disease, and
      cerebrovascular disease. CONCLUSIONS: Mid-term hospital readmissions are highly
      frequent in acute myocardial infarction survivors. Male sex, previous coronary
      heart disease, and the number of classical cardiovascular risk factors are the
      major risk predictors of this readmission. Our results highlight the need for
      improved medical care during acute myocardial infarction admission, integrated
      into secondary prevention programs.

PMID- 22133785
TI  - Influence of obesity and malnutrition on acute heart failure.
AB  - INTRODUCTION AND OBJECTIVES: Obesity is an independent risk factor for the
      development of heart failure. Several recent studies have found better outcomes
      of heart failure for obese patients, an observation termed as the "obesity
      paradox." On the other hand, the negative effect of malnutrition on the evolution
      of heart failure has also been clearly established. METHODS: Data from the
      Minimum Basic Data Set were analyzed for all patients discharged from all the
      departments of internal medicine in hospitals of the Spanish National Health
      System between the years 2006 and 2008. The information was limited to those
      patients with a primary or secondary diagnosis of heart failure. Patients with a
      diagnosis of obesity or malnutrition were identified. The mortality and
      readmission indexes of obese and malnourished patients were compared against the
      subpopulation without these diagnoses. RESULTS: A total of 370,983 heart failure
      admittances were analyzed, with 41,127 (11.1%) diagnosed with obesity and 4105
      (1.1%) with malnutrition. In-hospital global mortality reached 12.9% and the risk
      of readmission was 16.4%. Obese patients had a lower in-hospital mortality risk
      (odds ratio [OR]: 0.65, 95% confidence interval [95%CI]: 0.62-0.68) and early
      readmission risk (OR: 0.81, 95%CI: 0.78-0.83) than nonobese patients.
      Malnourished patients had a much higher risk of dying while in hospital (OR: 1.83
      95%CI: 1.69-1.97) or of being readmitted within 30 days after discharge (OR:
      1.39, 95%CI: 1.29-1.51), even after adjusting for possible confounding factors.
      CONCLUSIONS: Obesity in patients admitted for HF substantially reduces in
      hospital mortality risk and the possibility of early readmission, whereas
      malnutrition is associated with important increases in in-hospital mortality and
      risk of readmission in the 30 days following discharge.

PMID- 22133786
TI  - Pneumonectomy acutely after pediatric bilateral lung transplantation: management
      of communicating thoracic spaces.

PMID- 22133788
TI  - Histologic and functional evaluation of lungs reconditioned by ex vivo lung
      perfusion.
AB  - BACKGROUND: Only about 15% of donor lungs are considered suitable for
      transplantation (LTx). Ex vivo lung perfusion (EVLP) has been developed as a
      method to reassess and repair damaged lungs. We report our experience with EVLP
      in non-acceptable donor lungs and evaluate its ability to recondition these
      lungs. METHODS: We studied lungs from 16 brain-dead donors rejected for LTx.
      After harvesting, the lungs were stored at 4 degrees C for 10 hours and subjected
      to normothermic EVLP with Steen Solution (Vitrolife, Goteborg, Sweden) for 60
      minutes. For functional evaluation, the following variables were assessed:
      partial pressure of arterial oxygen (Pao(2)), pulmonary vascular resistance
      (PVR), and lung compliance (LC). For histologic assessment, lung biopsy was done
      before harvest and after EVLP. Tissue samples were examined under light
      microscopy. To detect and quantify apoptosis, terminal deoxynucleotide
      transferase-mediated deoxy uridine triphosphate nick-end labeling assay was used.
      RESULTS: Thirteen lung donors were refused for having impaired lung function. The
      mean Pao(2) obtained in the organ donor at the referring hospital was 193.7 mm Hg
      and rose to 489 mm Hg after EVLP. During EVLP, the mean PVR was 652.5
      dynes/sec/cm(5) and the mean LC was 48 ml/cm H(2)O. There was no significant
      difference between the mean Lung Injury Score before harvest and after EVLP.
      There was a trend toward a reduction in the median number of apoptotic cells
      after EVLP. CONCLUSIONS: EVLP improved lung function (oxygenation capacity) of
      organs considered unsuitable for transplantation. Lung tissue structure did not
      deteriorate even after 1 hour of normothermic perfusion.

PMID- 22133787
TI  - Withdrawal of proliferation signal inhibitors due to adverse events in the
      maintenance phase of heart transplantation.
AB  - BACKGROUND: The increasing use of proliferation signal inhibitors (PSIs) has
      raised the issue of their risk profile. We sought to determine the causes,
      incidence, risk factors, and consequences of withdrawal due to adverse events of
      PSIs in maintenance heart transplantation. METHODS: This was a retrospective
      study from 9 centers of the Spanish Registry for Heart Transplantation.
      Demographic, clinical, analytic, and evolution data were obtained for patients in
      whom a PSI (sirolimus or everolimus) was used between October 2001 and March
      2009. RESULTS: In the first year, 16% of 548 patients could not tolerate PSIs.
      This incidence rate stabilized to 3% to 4% per year thereafter. The most frequent
      causes for discontinuation were edema (4.7%), gastrointestinal toxicity (3.8%),
      pneumonitis (3.3%), and hematologic toxicity (2.0%). In multivariate analysis,
      withdrawal of PSI was related to the absence of statin therapy (p = 0.006),
      concomitant treatment with anti-metabolites (p = 0.006), a poor baseline renal
      function (p = 0.026), and multiple indications for PSI use (p = 0.04). Drug
      discontinuation was associated with a decline in renal function (p = 0.045) but
      not with an excess in mortality (p = 0.42). CONCLUSIONS: In this large cohort of
      maintenance heart transplant recipients taking a PSI, 16% withdrew treatment in
      the first year, and 25% had stopped PSI due to severe adverse events by the
      fourth year. This high rate of toxicity-related PSI withdrawal could limit the
      clinical utility of this otherwise novel class of immunosuppressive agents.

PMID- 22133789
TI  - [Management of targeted therapies in hemodialysis patients].
AB  - INTRODUCTION: The increased incidence of cancer in dialysis patients has been
      discussed since the mid 1970s. Furthermore, the emergence of targeted therapies
      (TT) requires oncologists, nephrologists and pharmacists to question themselves
      about the handling of these new classes of drugs in dialysis patients. While the
      cytotoxic drugs have been used in oncology for a long time, these new molecules
      are recent and clinical studies on their management in dialysis patients are
      missing. METHODS: We reviewed the international literature on the
      pharmacokinetics, efficacy, tolerance and dosage adjustment of TT used in
      hemodialysis cancer patients, using the following keywords: kidney; renal;
      dialysis; hemodialysis; end-stage renal disease and the name of each drug.
      RESULTS: As described for cytotoxic drugs, there are only case reports or series
      published in the international literature. However, it is possible to propose
      some recommendations on TT handling in dialysis patients. It is not necessary to
      adapt the dose of monoclonal antibodies in dialysis patients. But it is important
      to considerer that this "class effect" is not true for all the other classes of
      drugs. In fact, the pharmacokinetic of tyrosine kinase inhibitors varies from
      drug to drug. CONCLUSION: The use of TT is possible in dialysis patients.
      However, many drugs require special attention in dialysis. In addition, because
      these drugs are new, it is important that oncologists, nephrologists, and
      pharmacists remain up to date about the management of TT in dialysis patients.

PMID- 22133790
TI  - A horizon scan of global conservation issues for 2012.
AB  - Our aim in conducting annual horizon scans is to identify issues that, although
      currently receiving little attention, may be of increasing importance to the
      conservation of biological diversity in the future. The 15 issues presented here
      were identified by a diverse team of 22 experts in horizon scanning, and
      conservation science and its application. Methods for identifying and refining
      issues were the same as in two previous annual scans and are widely transferable
      to other disciplines. The issues highlight potential changes in climate,
      technology and human behaviour. Examples include warming of the deep sea,
      increased cultivation of perennial grains, burning of Arctic tundra, and the
      development of nuclear batteries and hydrokinetic in-stream turbines.

PMID- 22133791
TI  - Use of the Boston Ocular Surface Prosthesis in the management of severe
      periorbital thermal injuries: a case series of 10 patients.
AB  - PURPOSE: To report the use of the Boston Ocular Surface Prosthesis (BOSP) in
      patients with severe periorbital thermal injuries. DESIGN: Retrospective,
      interventional case series. PARTICIPANTS: Patients with severe periorbital
      thermal injuries treated with the BOSP. METHODS: Chart review of 10 consecutive
      patients (16 eyes) who sustained severe periorbital thermal injuries during
      combat missions in Iraq and Afghanistan and were treated for exposure keratopathy
      with the BOSP, a Food and Drug Administration-approved gas-permeable, scleral
      contact lens. MAIN OUTCOME MEASURES: Corneal epithelial defect healing,
      uncorrected and best-corrected visual acuity, and BOSP wear time. RESULTS:
      Exposure keratopathy occurred after severe periorbital thermal injuries and
      followed a predictable course of scar contracture. In all patients, vision
      threatening ocular surface disease developed as a result of chronic ocular
      exposure. Rehabilitation of the ocular surface was accomplished using the BOSP,
      with 10 of the 16 treated eyes achieving a corrected visual acuity of 20/70 or
      better. Five eyes achieved a best-corrected visual acuity of 20/40 or better. The
      BOSP also was used as a drug-delivery vehicle to treat corneal ulcers
      successfully in 6 eyes. The only eye that required penetrating keratoplasty was
      an early intervention believed to be a direct sequelae of the original thermal
      burn, rather than a failure of the BOSP regimen. The mean BOSP wear time was 16
      hours per day. CONCLUSIONS: The BOSP can play an important role in rehabilitation
      of the ocular surface for patients with severe periorbital thermal injuries and
      resultant exposure keratopathy. Use of the BOSP should be considered as a
      treatment option for these difficult cases of severe periorbital thermal
      injuries.

PMID- 22133792
TI  - Risk alleles in CFH and ARMS2 are independently associated with systemic
      complement activation in age-related macular degeneration.
AB  - PURPOSE: Systemic complement activation is associated with age-related macular
      degeneration (AMD) and has mainly been attributed to a risk allele in the
      complement factor H (CFH) gene. Whether other important AMD genes also influence
      complement activation is unclear. In the present case-control study, complement
      activity and concentrations of complement components and their activation
      products are measured in AMD patients and in unaffected controls and correlated
      with genetic variants in the CFH, ARMS2, C3, CFI, and CFB genes. DESIGN: Case
      control study. PARTICIPANTS: A cohort of 197 confirmed AMD patients and 150
      unaffected age-matched controls were recruited prospectively for the study.
      METHODS: Hemolytic complement assays (AP50, CP50, and LP50), complement
      components (C3, CFB, CFI, and CFH), and the activation products (C3d, C5a, and
      SC5b-9) were analyzed in serum or plasma. The DNA samples were genotyped for 5
      single nucleotide polymorphisms (SNPs) previously associated with AMD in the CFH,
      ARMS2, C3, CFB, and CFI genes. MAIN OUTCOME MEASURES: Complement concentrations
      and their associations with SNPs in the CFH, ARMS2, C3, CFB, and CFI genes.
      RESULTS: The AMD patients had increased activation of the alternative complement
      pathway (P = 0.003) and elevated levels of complement activation components C3d
      (P<0.0001) and C5a (P<0.0001), CFB (P<0.0001), and an increased C3d/C3 ratio
      (P<0.0001) calculated as a measure of C3 activation. While the CFH risk genotype
      was significantly associated with the elevated C3d/C3 ratios obtained, in the
      absence of CFH risk alleles the ARMS2 risk genotype also showed significantly
      increased levels of complement activation (P = 0.013). Furthermore, the carriers
      of the CFB protective allele had lower CFB concentrations. CONCLUSIONS: The
      current study found evidence showing that in AMD risk alleles in CFH and ARMS2
      are independently associated with complement activation. Especially the C3d/C3
      ratio seems to be a strong marker for AMD. The findings suggest that CFH and
      ARMS2 share a common pathway in the pathogenesis of AMD.

PMID- 22133793
TI  - Corneal densitometry as an indicator of corneal health.
AB  - PURPOSE: To establish prospectively the normal values of corneal density of
      healthy subjects using the Pentacam Scheimpflug system (Oculus, Inc., Wetzlar,
      Germany) and to investigate alteration in corneal density during active and
      healed stages of bacterial keratitis. DESIGN: Prospective, comparative case
      series. PARTICIPANTS AND CONTROLS: Sixty-four eyes of 40 healthy controls and 36
      eyes of 35 patients with bacterial keratitis were studied. METHODS: This study
      was conducted at the Queen's Medical Centre, Nottingham, United Kingdom. A
      Pentacam system was used to study corneal density. Corneal densitometry readings
      in subjects with bacterial keratitis were recorded during the active stage and 4
      to 6 weeks after complete healing. Densitometry was recorded at the site of
      infection and at a point in clear cornea furthest away from the infectious
      infiltrate. Corneal thickness also was measured. MAIN OUTCOME MEASURES:
      Densitometry values of normal cornea, at the site of corneal ulcer or abscess,
      and at a distant point of clear cornea during active and healed keratitis.
      RESULTS: The mean densitometry value of normal corneas was 12.3 +/- 2.4. In
      infectious keratitis, the densitometry values were greatest at the site of the
      active infection and significantly more than in controls. The densitometry values
      at the points of clear cornea furthest away from the site of infection also were
      significantly higher than in controls during active disease, but failed to return
      to normal values, despite complete resolution of infection. The density of the
      infiltrates was much higher than that of residual scars after healing of ulcers.
      No correlation was found between the pachymetry and the densitometry values.
      CONCLUSIONS: Densitometry of active infectious corneal infiltrates is more than
      that resulting from the corneal scarring after healing. Persistent increase in
      density of clear cornea furthest away from the focus of corneal infection
      suggests that the host response extends beyond the immediate area of infection
      and indeed may occur through the entire cornea. These changes persist beyond 4
      weeks of healing, which was the duration of follow-up of this study. Densitometry
      can be used as an objective measure of the corneal response to infection and to
      monitor response to therapy.

PMID- 22133794
TI  - Plaque radiotherapy for residual or recurrent iris melanoma after surgical
      resection in 32 cases.
AB  - PURPOSE: To evaluate plaque radiotherapy for management of residual or recurrent
      iris melanoma after surgical resection. DESIGN: Retrospective, nonrandomized
      interventional case series. PARTICIPANTS: We included 32 patients with residual
      or recurrent iris melanoma after surgical resection. INTERVENTION: Custom
      designed iodine-125 plaque radiotherapy. MAIN OUTCOME MEASURES: Tumor control,
      recurrence, poor visual acuity, enucleation, metastasis, and radiation
      complications. RESULTS: There were 32 eyes with residual (n = 12) or recurrent (n
      = 20) iris melanoma after surgical resection that were treated with iodine-125
      plaque radiotherapy. The residual melanoma was evident clinically in 3 cases and
      histopathologically in 9; plaque radiotherapy was delivered at a mean interval of
      2 months after resection. For the recurrent cases, the mean interval from initial
      tumor resection to detection of recurrence was 58 months, at which time plaque
      radiotherapy was applied. For all cases, the mean tumor basal diameter was 6 mm
      (range, 1-13) and thickness was 2 mm (range, 0.8-4.0) at the time of
      radiotherapy. Anterior chamber seeding was present in 26 (81%) eyes and glaucoma
      in 11 (34%) eyes. Visual acuity at presentation was good (20/20-20/50) in 27
      (84%), intermediate (20/60-20/150) in 3 (9%), and poor (<=20/200) in 2 eyes (6%).
      At 6 years after plaque radiotherapy, outcomes included complete tumor control in
      87%, poor visual acuity in 9%, enucleation in 13% (for reasons of tumor
      recurrence [n = 3] and severe glaucoma [n = 1]), and metastasis in 3%. At 6
      years, radiation complications included corneal epitheliopathy in 6%, scleral
      necrosis in 3%, cataract in 53%, elevated intraocular pressure (from tumor or
      radiotherapy) in 19%, and macular edema in 6%. CONCLUSIONS: Iodine-125 plaque
      radiotherapy is effective in the management of residual or recurrent iris
      melanoma after surgical resection, providing tumor control in 87% of patients at
      6 years and avoiding enucleation in most cases.

PMID- 22133795
TI  - Analysis of outcomes for intravitreal bevacizumab in the treatment of choroidal
      neovascularization secondary to ocular histoplasmosis.
AB  - PURPOSE: To assess the long-term outcomes of intravitreal bevacizumab (IVB) in
      the treatment of choroidal neovascularization (CNV) secondary to presumed ocular
      histoplasmosis syndrome (POHS). DESIGN: Retrospective, comparative case series.
      PARTICIPANTS: Interventional series of 150 eyes in 140 patients treated for
      subfoveal or juxtafoveal CNV secondary to POHS from January 2006 to January 2010.
      INTERVENTION: Intravitreal bevacizumab monotherapy or combination IVB and
      verteporfin photodynamic therapy (IVB/PDT). MAIN OUTCOME MEASURES: Visual acuity
      (VA) at 12 and 24 months was analyzed. Secondary outcome measures included the
      number of injections per year and treatment-free intervals. RESULTS: A total of
      117 eyes received IVB monotherapy, and 34 eyes underwent combination IVB/PDT
      treatment. For all patients, the average pretreatment logarithm of minimum angle
      of resolution (logMAR) was 0.63 (Snellen equivalent 20/86) with a 12-month logMAR
      VA of 0.45 (Snellen equivalent 20/56) and a 24-month logMAR VA of 0.44 (Snellen
      equivalent 20/55). The mean follow-up was 21.1 months with an average of 4.24 IVB
      injections per year. There was no significant difference in initial VA, VA at 12
      months, VA at 24 months, or number of eyes with a 3-line gain between the IVB
      monotherapy and IVB/PDT groups. Thirty-eight percent (39/104) of eyes gained 3
      lines or more, and 81.2% (84/104) of subjects had maintained or improved their
      starting VA at 1 year. The proportion of subjects maintaining a 3-line gain in VA
      was relatively preserved at 2 years (29.8%, 17/57) and 3 years (30.3%, 10/32)
      follow-up. There was no increase in the proportion of subjects losing 3 lines or
      more over 3 years of follow-up. CONCLUSIONS: There is no significant difference
      in VA outcomes between IVB monotherapy versus IVB/PDT combination therapy. The
      use of IVB alone or in combination with PDT results in significant visual
      stabilization in the majority of patients with CNV secondary to POHS.

PMID- 22133796
TI  - A five-year study of slotted eye plaque radiation therapy for choroidal melanoma:
      near, touching, or surrounding the optic nerve.
AB  - OBJECTIVE: To evaluate slotted eye plaque radiation therapy for choroidal
      melanomas near the optic disc. DESIGN: A clinical case series. PARTICIPANTS:
      Twenty-four consecutive patients with uveal melanomas that were near, touching,
      or surrounding the optic disc. INTERVENTION: Slotted eye plaque radiation
      therapy. MAIN OUTCOME MEASURES: Recorded characteristics were related to patient,
      clinical, and ophthalmic imaging. Data included change in visual acuity, tumor
      size, recurrence, eye retention, and metastasis. RESULTS: From 2005 to 2010, 24
      consecutive patients were treated with custom-sized plaques with 8-mm-wide,
      variable-depth slots. Radiation doses ranged from 69.3 to 163.8 Gy (mean, 85.0
      Gy) based on delivering a minimum tumor dose of 85 Gy. All treatments were
      continuously delivered over 5 to 7 days. Mean patient age at presentation was 57
      years. Tumors were within 1.5 mm of the optic nerve (n = 3, 13%), juxtapapillary
      (n = 6, 25%), touching >=180 degrees (n = 7, 29%), or circumpapillary (n = 8,
      33%). Ultrasound revealed dome-shaped tumors in 79% of patients, collar-button
      tumors in 17% of patients, irregular tumor in 1 patient (4%), and intraneural
      invasion in 2 patients. Mean initial largest basal dimension was 11.0 mm
      (standard deviation [SD] +/- 3.5 mm; median, 11.4 mm; range, 5.9-16.4 mm). Mean
      initial tumor thickness was 3.5 mm (SD +/- 1.7 mm; median, 3.0 mm; range, 1.4-6.9
      mm). Initial visual acuities were a median 20/25 (range, 20/20 to hand motions)
      and decreased to a median 20/40 (range, 20/20 to no light perception). At a mean
      follow-up of 23 months, 12 patients required periodic intravitreal bevacizumab to
      suppress radiation optic neuropathy (RON) or maculopathy. To date, there has been
      a 100% local control rate. No patients have required secondary enucleation for
      recurrence or neovascular glaucoma. No patients have developed metastasis.
      CONCLUSIONS: Slotted plaque radiation therapy allows peripapillary,
      juxtapapilary, and circumpapillary choroidal melanomas (and a safety margin) to
      be included in the radiation targeted zone. Normalization of the plaque position
      beneath the tumor appears to increase RON and improve local control.

PMID- 22133797
TI  - Rates of change in the visual field and optic disc in patients with distinct
      patterns of glaucomatous optic disc damage.
AB  - PURPOSE: To investigate the rate of visual field and optic disc change in
      patients with distinct patterns of glaucomatous optic disc damage. DESIGN:
      Prospective longitudinal study. PARTICIPANTS: A total of 131 patients with open
      angle glaucoma with focal (n = 45), diffuse (n = 42), and sclerotic (n = 44)
      optic disc damage. METHODS: Patients were examined every 4 months with standard
      automated perimetry (SAP, SITA Standard, 24-2 test, Humphrey Field Analyzer, Carl
      Zeiss Meditec, Dublin, CA) and confocal scanning laser tomography (CSLT,
      Heidelberg Retina Tomograph, Heidelberg Engineering GmbH, Heidelberg, Germany)
      for a period of 4 years. During this time, patients were treated according to a
      predefined protocol to achieve a target intraocular pressure (IOP). Rates of
      change were estimated by robust linear regression of visual field mean deviation
      (MD) and global optic disc neuroretinal rim area with follow-up time. MAIN
      OUTCOME MEASURES: Rates of change in MD and rim area. RESULTS: Rates of visual
      field change in patients with focal optic disc damage (mean -0.34, standard
      deviation [SD] 0.69 dB/year) were faster than in patients with sclerotic (mean 
      0.14, SD 0.77 dB/year) and diffuse (mean +0.01, SD 0.37 dB/year) optic disc
      damage (P = 0.003, Kruskal-Wallis). Rates of optic disc change in patients with
      focal optic disc damage (mean -11.70, SD 25.5 *10(-3) mm(2)/year) were faster
      than in patients with diffuse (mean -9.16, SD 14.9 *10(-3) mm(2)/year) and
      sclerotic (mean -0.45, SD 20.6 *10(-3) mm(2)/year) optic disc damage, although
      the differences were not statistically significant (P = 0.11). Absolute IOP
      reduction from untreated levels was similar among the groups (P = 0.59).
      CONCLUSIONS: Patients with focal optic disc damage had faster rates of visual
      field change and a tendency toward faster rates of optic disc deterioration when
      compared with patients with diffuse and sclerotic optic disc damage, despite
      similar IOP reductions during follow-up.

PMID- 22133798
TI  - Lacrimal gland ductulitis caused by probable Actinomyces infection.
AB  - OBJECTIVE: To describe the clinical characteristics and management of a group of
      patients who had chronic mucopurulent conjunctivitis that was probably due to
      Actinomyces infection of the lacrimal gland ductules. DESIGN: A retrospective,
      interventional case series. PARTICIPANTS: Seven patients (2 male; 29%) between 34
      and 52 years of age (mean, 48.7 years; median, 49 years) who presented to the
      lacrimal clinic. INTERVENTION: Surgical excision of the infective focus (6 cases)
      or fenestration and expression of infective debris (1 case) from the affected
      lacrimal gland ductule--typically the most inferolateral of the ductules. MAIN
      OUTCOME MEASURES: The clinical features of this previously unrecognized cause of
      chronic conjunctivitis and its response to treatment. RESULTS: All cases settled
      rapidly after surgery. There was often a major delay in diagnosis, with the
      patients having symptoms for between 2 and 42 months before referral (mean, 13.3
      months; median, 9 months); 5 patients received prolonged or ineffectual topical
      medical therapy before referral. CONCLUSIONS: Infective lacrimal gland
      ductulitis, commonly from Actinomyces infection, should be considered in patients
      with unexplained chronic mucopurulent conjunctivitis; the condition settles
      rapidly with surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 22133799
TI  - Epidemiology and clinical presentation of pandemic influenza A (H1N1) among
      hospitalized children in Kuwait.
AB  - OBJECTIVE: To describe the epidemiological and clinical characteristics of
      children hospitalized for the 2009 influenza A H1N1 infection in Kuwait.
      MATERIALS AND METHODS: A retrospective chart review of hospitalized children with
      laboratory-confirmed influenza A H1N1 infection in two hospitals in Kuwait was
      conducted. Epidemiological characteristics, clinical features, risk factors for
      severe disease, complications and mortality were analyzed. RESULTS: The medical
      records of 197 children hospitalized for the 2009 pandemic H1N1 infection from
      August 2009 to January 2010 were reviewed. The majority of the children (104;
      52.8%) were admitted during the month of October. The median age was 2 years.
      Most of the admitted children were in two age categories: 64 infants <=1 year
      (32%) and 62 schoolchildren >5 years (31%). The most frequent presentations were
      fever in 193 (98%), cough in 155 (79%) and runny nose in 105 (53%) cases. The
      majority of the admitted children (109; 55%) had been previously healthy. All
      children received an antiviral agent (oseltamivir), and antibiotics were
      administered to 147 (75%). Bacterial co-infections occurred in 3 (1.5%) of all
      hospitalized children. Six (3%) children were admitted to the intensive care
      unit, of whom 4 (66%) required artificial ventilation. There was only 1
      mortality. CONCLUSIONS: The pandemic H1N1 infection was associated with a wide
      spectrum of clinical manifestations. The majority of hospitalized children had
      previously been healthy. Most of the admitted children had an uncomplicated
      clinical course.

PMID- 22133800
TI  - Morphological changes of the lateral meniscus in end-stage lateral compartment
      osteoarthritis of the knee.
AB  - OBJECTIVE: The aim of this study was to evaluate the morphological changes of the
      lateral meniscus in end-stage lateral compartment osteoarthritis (OA) of the
      knee. METHODS: One hundred fifty-eight knee joints from 133 patients that
      subsequently underwent total knee joint arthroplasty from January 2008 to
      December 2009 were enrolled. There were 26 men and 107 women. Their ages ranged
      from 56 to 81 (mean 67.4 +/- 6.5 years). All study participants had complete
      obliteration of the lateral joint space identified by weight-bearing radiography.
      Meniscal position was assessed by measuring meniscal subluxation and meniscal
      height. The meniscal morphology was assessed using a modification of the whole
      organ magnetic resonance imaging score (WORMS). The frequency of different
      meniscal morphology and their respective positions was calculated. RESULTS: The
      predominant type (42.4%, 53.8% and 52.5% in the anterior horn, mid-body and
      posterior horn, respectively) of abnormal meniscal morphology was a complete
      maceration/destruction or complete resection. The anterior horn of non-macerated
      lateral meniscus was more subluxed than that of the non-macerated medial meniscus
      in patients with lateral OA. CONCLUSION: This study suggests that the lateral
      meniscus in persons with end-stage lateral OA are mostly macerated or destroyed.
      Also, unlike isolated end-staged medial compartment OA, the anterior horn of the
      lateral meniscus in isolated end-stage lateral OA is commonly affected.

PMID- 22133801
TI  - Can ballooning of the levator hiatus be determined clinically?
AB  - OBJECTIVE: The objective of the study was to determine whether genital hiatus
      (gh) and perineal body (pb), measured using the pelvic organ prolapse
      quantification system of the International Continence Society, are predictive of
      an abnormally distensible levator hiatus on ultrasound and of objective prolapse
      and/or prolapse symptoms. STUDY DESIGN: The design of the study included datasets
      of 188 urogynecology patients assessed in a cross-sectional retrospective study.
      RESULTS: Gh and pb, as well as gh plus pb, were strongly associated with symptoms
      and signs of prolapse and with hiatal area on ultrasound. The sum of gh and pb
      was superior in predictive performance to individual measures for symptoms (P <
      .001) and signs of prolapse (P < .001). Gh plus pb equaled the hiatal area on
      ultrasound (area under the curve, 0.886; 95% confidence interval, 0.828-0.945 vs
      0.867; 95% confidence interval, 0.808-0.926) for predicting objective prolapse.
      Optimal sensitivity (80%) and specificity (81%) was reached with a cutoff of 7 cm
      for gh plus pb. CONCLUSION: A cutoff of 7 cm for gh plus pb measured on Valsalva
      is proposed as a clinical definition of excessive levator hiatal distensibility.

PMID- 22133802
TI  - Sonographic cervical length, vaginal bleeding, and the risk of preterm birth.
AB  - OBJECTIVE: We sought to evaluate the contributions of vaginal bleeding and
      cervical length to the risk of preterm birth. STUDY DESIGN: This was a secondary
      analysis of a cohort study designed to study predictors of preterm birth. The
      study included 2988 women with singleton gestations. Women underwent midtrimester
      transvaginal ultrasound assessment of cervical length and were queried regarding
      first- and second-trimester vaginal bleeding. RESULTS: There was a significant
      second-order relation between cervical length and preterm birth (P < .001, P =
      .005). Women with vaginal bleeding were at higher risk of preterm birth (odds
      ratio, 1.5; 95% confidence interval, 1.3-2.0). There was a significant
      interaction between cervical length and vaginal bleeding (P = .015). After
      accounting for cervical length and interaction, the adjusted odds ratio for
      vaginal bleeding and preterm birth was 4.8 (95% confidence interval, 1.89-12.4; P
      = .001). CONCLUSION: The magnitude of risk of preterm birth associated with
      sonographic cervical length depends on a woman's history of first- and second
      trimester vaginal bleeding.

PMID- 22133803
TI  - Overexpression of TDP-43 causes partially p53-dependent G2/M arrest and p53
      independent cell death in HeLa cells.
AB  - It has been hypothesized that the dysregulation of transactive response DNA
      binding protein-43 (TDP-43) in neurons is closely linked to the pathogenesis of
      amyotrophic lateral sclerosis and frontotemporal lobar degeneration with
      ubiquitinated inclusions. However, it remains undefined whether the dysregulation
      of TDP-43 in non-neuronal cells, such as glial cells, contributes to the
      pathogenesis of these neurodegenerative diseases. Primarily using HeLa cells, we
      show that a low-grade overexpression of TDP-43, 2- to 5-fold greater than
      endogenous expression, which is thought to mimic the gain of function of TDP-43,
      induced cell cycle arrest at the G2/M phase and cell death in cultured non
      neuronal cells. Since the activation of p53 may induce G2/M arrest and/or cell
      death in many abnormal situations, we examined the mechanism underlying G2/M
      arrest from the standpoint of p53 regulation. It was determined that the TDP-43
      induced G2/M arrest was attenuated, while TDP-43-induced death was not
      attenuated, in cells in which the p53 function was compromised. These data
      collectively indicate that TDP-43 causes G2/M arrest in a partially p53-dependent
      manner and it causes cell death in a p53-independent manner in cycling cells.
      Because it is likely that the impaired proliferation in glial cells causes a
      decrease in the neuron-supporting ability, these findings further suggests that
      the gain of function of TDP-43 may cause neurotoxicity by inducing cell cycle
      arrest and death in glial cells.

PMID- 22133804
TI  - The leucine-rich repeats of LINGO-1 are not required for self-interaction or
      interaction with the amyloid precursor protein.
AB  - LINGO-1 (leucine rich repeat and Ig domain containing Nogo receptor interacting
      protein-1) is a central nervous system transmembrane protein which simultaneously
      interacts with the Nogo-66 receptor and p75(NTR) or TROY on neurons to form a
      receptor complex responsible for myelin-mediated neurite outgrowth inhibition. On
      oligodendroglial cells, LINGO-1 interacts with p75(NTR) to constitutively inhibit
      multiple aspects of oligodendrocyte differentiation. Recently, LINGO-1 was
      identified as an in vivo interacting partner of the amyloid precursor protein
      (APP) and, correspondingly, cellular LINGO-1 expression was found to augment the
      release of the Abeta peptide, the potential causative agent of Alzheimer's
      disease. In addition, the recombinant LINGO-1 ectodomain has been shown to self
      interact in solution and after crystallisation. Here, we have used deletional
      mutagenesis to identify the regions on LINGO-1 that are involved in homo- and
      heterotypic interactions. We have found that the N-terminal region containing the
      leucine-rich repeats along with the transmembrane and cytoplasmic domains of
      LINGO-1 are not required for self-interaction or interaction with APP.

PMID- 22133805
TI  - Calcium-binding proteins and GFAP immunoreactivity alterations in murine
      hippocampus after 1 month of exposure to 835 MHz radiofrequency at SAR values of
      1.6 and 4.0 W/kg.
AB  - Widespread use of wireless mobile communication has raised concerns of adverse
      effect to the brain owing to the proximity during use due to the electromagnetic
      field emitted by mobile phones. Changes in calcium ion concentrations via binding
      proteins can disturb calcium homeostasis; however, the correlation between
      calcium-binding protein (CaBP) immunoreactivity (IR) and glial cells has not been
      determined with different SAR values. Different SAR values [1.6 (E1.6 group) and
      4.0 (E4 group) W/kg] were applied to determine the distribution of calbindin D28
      k (CB), calretinin (CR), and glial fibrillary acidic protein (GFAP) IR in murine
      hippocampus. Compared with sham control group, decreased CB and CR IRs, loss of
      CB and CR immunoreactive cells and increased GFAP IR exhibiting hypertrophic
      cytoplasmic processes were noted in both experimental groups. E4 group showed a
      prominent decrement in CB and CR IR than the E1.6 group due to down-regulation of
      CaBP proteins and neuronal loss. GFAP IR was more prominent in the E4 group than
      the E1.6 group. Decrement in the CaBPs can affect the calcium-buffering capacity
      leading to cell death, while increased GFAP IR and changes in astrocyte
      morphology, may mediate brain injury due to radiofrequency exposure.

PMID- 22133806
TI  - Inhibition of sensory neuronal TRPs contributes to anti-nociception by butamben.
AB  - Butamben (n-butyl-p-aminobenzoic acid) is a pain-relieving local anesthetic for
      topical use. Blockade of voltage-gated channel expressed in the peripheral
      sensory neurons has been suggested as a mechanism of action. Its effects on
      another sensory neuronal channel family, transient receptor potential (TRP) have
      remained unclear. In this study we attempted to address this question using six
      sensory neuronal TRP channel-expressing heterologous systems, cultured sensory
      neurons and TRP-mediated acute animal pain tests. In Ca(2+) imaging and whole
      cell electrophysiology, TRPA1 and TRPV4 were blocked by micromolar butamben.
      Butamben also activated TRPA1 at millimolar concentrations. The inhibitory
      effects on the two TRP channels were reproducible in sensory neurons. Moreover,
      butamben attenuated acute animal pain behaviors in a TRPA1- or TRPV4-dependent
      manner. Para-aminobenzoic acid (PABA), an analog of a simpler chemical structure,
      displayed similar in vitro and in vivo properties, suggestive that chemical
      structure is important for the two TRP-specificity. Our findings suggest that
      inhibition of TRPA1 and TRPV4 contribute to the peripheral analgesic mechanisms
      of butamben.

PMID- 22133807
TI  - Inhibition of sonic hedgehog signaling aggravates brain damage associated with
      the down-regulation of Gli1, Ptch1 and SOD1 expression in acute ischemic stroke.
AB  - Oxidative and cytotoxic damage play an important role in cerebral ischemic
      pathogenesis and may represent a target for treatment. Recent studies have
      indicated that sonic hedgehog (Shh) signaling could protect neurons against
      oxidative stress by increasing superoxide dismutase 1 (SOD1) activity. Glioma
      associated oncogene homolog 1 (Gli1) and patched-1 (Ptch1) are both components
      and transcriptional targets of the Shh pathway. Here, we designed this study to
      determine the effect of inhibition of Shh pathway on the development of cerebral
      ischemia injury. Male, Sprague-Dawley rats were subjected to permanent middle
      cerebral artery occlusion (pMCAO). Cyclopamine (0.18mg/kg), the classical
      inhibitor of Shh signaling, was stereotactic injected into the lateral cerebral
      ventricle immediately after pMCAO. At 24h neurological deficit was evaluated
      using a modified six point scale; brain water content was measured; infarct size
      was analyzed with 2,3,5-triphenyltetrazolium chloride (TTC).
      Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR),
      Western Blotting and activity assay were used to analyze the expression of Gli1,
      Ptch1 and SOD1. Compared with Vehicle group, cyclopamine down-regulated Gli1,
      Ptch1 and SOD1 in pMCAO-affected brain tissue (P<0.05), and increased infarct
      volume (P<0.05), brain water content (P<0.05) and behavioral deficits (P<0.05).
      Collectively, the present results suggest that inhibition of Shh signaling
      pathway exacerbated rat ischemic damage caused by pMCAO, which may be correlated
      with down-regulated expression of Gli1, Ptch1 and SOD1.

PMID- 22133808
TI  - Orally administered L-ornithine reduces restraint stress-induced activation of
      the hypothalamic-pituitary-adrenal axis in mice.
AB  - In a previous study, we confirmed that orally administered L-ornithine can be
      transported into the brain of mice. In addition, orally administered L-ornithine,
      within a limited dose range, had an anxiolytic-like effect in the elevated plus
      maze test. However, the mechanism by which orally administered L-ornithine
      reduced the stress response in mice is still unclear. Experiment 1 determined
      whether orally administered L-ornithine could reduce the stress-induced
      activation of hypothalamic-pituitary-adrenal axis. Mice were orally administered
      L-ornithine (0, 0.75, 1.5 and 3 mmol/10 ml/kg, p.o.), and restrained for 30 min
      from 30 min post administration. There was a significant decrease in the
      corticosterone levels in the group receiving 0.75 mmol of L-ornithine compared to
      the control group. In Experiment 2, the effect of orally administered L-ornithine
      (0 and 0.75 mmol/10 ml/kg, p.o.) on endogenous monoamine release was investigated
      using in vivo microdialysis. Only the monoamines metabolites 5
      hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC) and
      homovallinic acids (HVA) were detected in the present study. Dialysate
      concentrations of 5-HIAA, DOPAC and HVA were not significantly changed
      immediately after administration of L-ornithine and restraint stress. In
      conclusion, changes of corticosterone concentrations by orally administered L
      ornithine were not related to alterations in brain monoamine metabolisms.

PMID- 22133809
TI  - Pattern recognition receptors involved in the inflammatory attenuating effects of
      soybean isoflavone in beta-amyloid peptides 1-42 treated rats.
AB  - Pattern recognition receptors (PRRs) play important roles in the inflammatory
      responses to Alzheimer's disease (AD). Our previous study indicated that soybean
      isoflavone (SIF) exhibited anti-inflammatory effect in rats treated by beta
      amyloid peptides1-42 (Abeta1-42). In present study, we further detected the
      effects of SIF against inflammation caused by Abeta1-42 treatment in rats. Serum
      inflammatory mediators and neurotrophic factors including transforming growth
      factor-beta (TGF-beta), inducible nitric oxide synthase (iNOS), brain-derived
      neurotrophic factor (BDNF) and S100beta were detected by enzyme-like
      immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction (RT
      PCR) and western blot methods were applied for detecting mRNA and protein
      expression of interleukin-1beta (IL-1beta), iNOS, tumor necrosis factor-alpha
      (TNF-alpha), TGF-beta, BDNF, S100beta, myeloid differentiation factor88 (Myd88),
      Toll-like receptor2 (TLR2), formyl peptide receptors (FPRs), inhibitor kappaB
      kinase (IKK) and inhibitor kappaB-alpha (IkappaB-alpha) in rat's brain tissue.
      Our results indicated that SIF could reduce the production of IL-1beta, TNF-alpha
      and iNOS induced by Abeta1-42 in serum and brain of rats. SIF also significantly
      reversed Abeta1-42-induced up-regulation of TLR2, FPR, Myd88, IKK and decreased
      IkappaB-alpha mRNA and protein expressions in rats. These results suggested that
      TLR2 and FPR might involve in the inflammatory process induced by Abeta1-42
      treatment, and SIF was an efficiency compound in reversing the inflammation
      caused by Abeta1-42 treatment.

PMID- 22133810
TI  - Cntnap2 expression in the cerebellum of Foxp2(R552H) mice, with a mutation
      related to speech-language disorder.
AB  - Foxp2(R552H) knock-in (KI) mice carrying a mutation related to human speech
      language disorder exhibit impaired ultrasonic vocalization and poor Purkinje cell
      development. Foxp2 is a forkhead domain-containing transcriptional repressor that
      associates with its co-repressor CtBP; Foxp2(R552H) displays reduced DNA binding
      activity. A genetic connection between FOXP2 and CNTNAP2 has been demonstrated in
      vitro, but not in vivo. Here we show that Cntnap2 mRNA levels significantly
      increased in the cerebellum of Foxp2(R552H) KI pups, although the cerebellar
      population of Foxp2-positive Purkinje cells was very small. Furthermore, Cntnap2
      immunofluorescence did not decrease in the poorly developed Purkinje cells of
      Foxp2(R552H) KI pups, although synaptophysin immunofluorescence decreased.
      Cntnap2 and CtBP were ubiquitously expressed, while Foxp2 co-localized with CtBP
      only in Purkinje cells. Taken together, these observations suggest that Foxp2 may
      regulate ultrasonic vocalization by associating with CtBP in Purkinje cells;
      Cntnap2 may be a target of this co-repressor.

PMID- 22133811
TI  - A rapid survival assay to measure drug-induced cytotoxicity and cell cycle
      effects.
AB  - We describe a rapid method to accurately measure the cytotoxicity of mammalian
      cells upon exposure to various drugs. Using this assay, we obtain survival data
      in a fraction of the time required to perform the traditional clonogenic survival
      assay, considered the gold standard. The dynamic range of the assay allows
      sensitivity measurements on a multi-log scale allowing better resolution of
      comparative sensitivities. Moreover, the results obtained contain additional
      information on cell cycle effects of the drug treatment. Cell survival is
      obtained from a quantitative comparison of proliferation between drug-treated and
      untreated cells. During the assay, cells are treated with a drug and, following a
      recovery period, allowed to proliferate in the presence of bromodeoxyuridine
      (BrdU). Cells that synthesize DNA in the presence of BrdU exhibit quenched
      Hoechst fluorescence, easily detected by flow cytometry; quenching is used to
      determine relative proliferation in treated vs. untreated cells. Finally, this
      assay can be used in high-throughput format to simultaneously screen multiple
      cell lines and drugs for accurate measurements of cell survival and cell cycle
      effects after drug treatment.

PMID- 22133812
TI  - Perioperative and postoperative complications of single-level minimally invasive
      transforaminal lumbar interbody fusion in elderly adults.
AB  - As the population ages, more elderly patients will develop painful degenerative
      lumbar pathology requiring lumbar fusion for treatment. Unfortunately,
      traditional techniques for lumbar fusion have been associated with increased
      morbidity and mortality in elderly patients. Minimally invasive transforaminal
      lumbar interbody fusion (TLIF) has been associated with fewer complications;
      however, little specific to the elderly population has been published. Thus, we
      performed a retrospective analysis on 84 consecutive patients (<65 years, young-
      45 patients; >= 65 years, elderly--39 patients) who underwent single-level,
      minimally invasive TLIF between October 2007 and December 2010. Hospital records,
      including operative notes, progress notes, and discharge summaries, were reviewed
      for patient demographics, procedures, disposition, and perioperative and
      postoperative complications. There was no significant difference between the
      young and elderly patients with respect to the total number of major, minor, or
      major and minor complications. Likewise, there was no significant difference
      between the two groups with respect to the number of patients experiencing one or
      more major, minor, or major and minor complications. The overall rate of
      experiencing at least one perioperative or postoperative complication was 16.33%
      for young patients and 20.00% in the elderly cohort (p = 0.7748). Thus, elderly
      patients with single-level degenerative lumbar pathology requiring fusion are not
      at increased risk of perioperative and postoperative complications compared to
      younger patients when undergoing single-level, minimally invasive TLIF.

PMID- 22133813
TI  - A reappraisal of the common carotid artery as an access site in interventional
      procedures for acute stroke therapies.
AB  - The cervical approach was the first to be used by neuroangiography pioneers, but
      due to limited access, drawbacks, and significant complications it was surpassed
      long ago in favor of the femoral approach. However, common carotid access can be
      a valuable alternative to femoral access in selected neuroendovascular cases,
      particularly in emergency procedures involving one of the carotid arteries when
      the femoral approach is impossible or contraindicated. We describe the successful
      use of carotid artery access for the treatment of acute stroke in a patient in
      whom common carotid artery and internal carotid artery tortuosity prevented the
      delivery of endovascular therapy to the middle cerebral artery via femoral artery
      access. Endovascular neurosurgeons should be familiar with percutaneous carotid
      artery access to provide comprehensive endovascular care to the growing subset of
      patients with complex vascular anatomy.

PMID- 22133814
TI  - Long-term lack of progression after initial treatment of idiopathic hypertrophic
      pachymeningitis.
AB  - Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare inflammatory
      disease which is sometimes difficult to diagnose and can lead to
      misinterpretations of the clinical and imaging findings. The main clinical
      manifestations are headache, ataxia and cranial nerve palsy. In most of the
      reported patients continuous medication is needed to avoid disease recurrence. We
      present a female patient with an 8-year follow-up, no clinical regression and no
      need for any further medical treatment. Even though most patients with IHCP
      experience recurrence after diagnosis and initial treatment there were no
      clinical or imaging signs of relapse in our patient. Our patient is still not
      under any medical or surgical treatment due to the lack of any significant
      symptoms.

PMID- 22133815
TI  - Levetiracetam compared to phenytoin for the prevention of postoperative seizures
      after craniotomy for intracranial tumours in patients without epilepsy.
AB  - Anticonvulsant drugs are frequently given after craniotomy. Phenytoin (PHT) is
      the most commonly used agent; levetiracetam (LEV) is a new anticonvulsant drug
      with fewer side effects. To compare the incidence of seizures in patients
      receiving either prophylactic PHT or LEV perioperatively, 971 patients undergoing
      a craniotomy were analysed retrospectively during a 2-year period. PHT was used
      routinely and LEV was administered when PHT was contraindicated. Seizures
      documented during the first 7 days after craniotomy were considered. A total of
      235 patients were treated with an antiepileptic drug: 81 patients received LEV,
      and 154 patients, PHT. Two patients receiving LEV (2.5%) and seven receiving PHT
      (4.5%) had a seizure despite this treatment. No patient had a documented side
      effect or drug interaction. The data show that LEV may be an alternative option
      in patients with contraindications to PHT.

PMID- 22133816
TI  - Acute transverse myelitis as a rare manifestation of Campylobacter diarrhoea with
      concomitant disruption of the blood brain barrier.
AB  - We describe a case of acute transverse myelitis following Campylobacter diarrhoea
      in an adult. The patient presented with diplegia due to a longitudinal spinal
      cord lesion. The CSF demonstrated an aseptic meningitis. Oligoclonal bands and C.
      jejuni-specific IgG were detected in serum and cerebrospinal fluid at the
      beginning of the neurological illness. The patient was treated with antimicrobial
      therapy and steroids. A near full recovery was made and there were no relapses.
      C. jejuni is strongly implicated in the aetiology of acute motor axonal
      neuropathy and Miller Fisher syndrome through molecular mimicry of neuronal
      gangliosides. These gangliosides are expressed throughout the nervous system yet
      C. jejuni related central nervous system disease is exceedingly rare. We conclude
      that disruption of the blood-brain barrier was the key event in the pathogenesis
      of immune mediated post-infectious myelitis in our patient.

PMID- 22133817
TI  - The ketogenic diet and the QT interval.
AB  - Cardiac complications have been rarely reported associated with the ketogenic
      diet. Prolonged QT interval in the electrocardiogram and torsades de pointes
      arrhythmias have been described in a few cases. The effect of the ketogenic diet
      on QT interval has not been systematically evaluated. We obtained serial
      electrocardiograms in our patients on the ketogenic diet to look for changes in
      the mean QT interval. Twenty seven children aged 6 months to 5 years with
      refractory epilepsy were enrolled. Classic ketogenic diet was introduced using a
      non-fasting gradual initiation protocol. All patients were supplemented with oral
      calcium and selenium. Electrocardiograms were obtained at baseline and after 1,
      3, 6, and 12 months on the ketogenic diet. There was no statistically significant
      change in the corrected QT interval over time. There were no ST segment changes
      or dysrhythmias in any of the electrocardiograms.

PMID- 22133818
TI  - Primary position upbeat nystagmus.
AB  - Primary position upbeat nystagmus is a rare clinical finding. We report a patient
      with clinically isolated syndrome suggestive of multiple sclerosis who presented
      with primary position upbeat nystagmus. MRI revealed a demyelinating lesion in
      the lower medulla, which affected the nucleus intercalatus; this type of lesion
      inhibits the flocculovestibular inhibitory pathway, thereby causing upbeat
      nystagmus. Nystagmus still persisted after pulsed corticosteroid therapy. This
      could be due to a loss of central adaptation of the vestibulo-ocular system in
      our patient, because of more diffuse brainstem damage, shown on vestibular-evoked
      myogenic potentials as delayed latencies on both sternocleidomastoid muscles and
      a conduction block for the left extraocular muscles.

PMID- 22133819
TI  - [A history of the research on bone metabolism for the past 50 years in Japan and
      a memory of Dr. Hirotoshi Morii].
AB  - It has been 20 years since the monthly Journal "CLINICAL CALCIUM" was published
      in November, 1991. This review Journal edited by Drs. Hirotoshi Morii and Yoshio
      Yazaki has contributed a lot to the understanding of the importance of calcium in
      bone and cardiovascular systems. This article describes a history of the research
      on bone metabolism for the past 50 years in Japan. Also, a memory of my dear
      friend, Hirotoshi Morii, is retraced.

PMID- 22133820
TI  - [Professor Morii and my academic life].
AB  - Emeritus Professor Hirotoshi Morii was an important mentor in my academic life,
      who was a chief editor of CLINICAL CALCIUM with Professor Yoshio Yazaki for a
      long time. In the study of dopamine-beta-hydroxylase, hyperthyroidism was able to
      prove hypotonic status for sympathetic nerve system by his valuable suggestion,
      though this condition was believed to be hypersympathetic till 1974 when my paper
      was published in Journal of Clinical Endocrinology and Metabolism. His suggestion
      struck me at that time. And this experience continues to give me an active power
      through my academic life.

PMID- 22133821
TI  - [Kanji character "sho" was first used for Japanese nomenclature of osteoporosis
      in 1897, the Meiji era].
AB  - The roughness and weakness of bone was really expressed by the character of
      "sho", which means the sight through the fine small leaves of pinetree in old
      Japabese seenery.

PMID- 22133822
TI  - [Bone and calcium update; research of calcium metabolism on cardiovascular system
      update. Calcium channel blocker update].
AB  - Voltage-dependent calcium channels are divided into L type, T type, and N type. L
      type calcium channel blockers are widely used for treatment of hypertension and
      cardiovascular diseases. However, recent experimental and clinical findings
      suggest that not only L type calcium channel but also T and N type calcium
      cannels are possibly involved in cardiovascular diseases, through activation of
      sympathetic nervous system or aldosterone release. Therefore, it is proposed that
      L type calcium channel blockade combined with T type or N type calcium channel
      blockade may have additive benefits in preventing cardiovascular and renal
      diseases. Further future study is needed to clarify class effect and drug effect
      of each calcium channel blocker.

PMID- 22133823
TI  - [Bone and calcium update; diagnosis and therapy of bone metabolism disease
      update. Calcification of atherosclerotic plaques: mechanism and clinical
      significance].
AB  - Vascular calcification is an important problem in the patients with diabetes and
      chronic kidney disease (CKD) , and contributes to the increased risk of
      cardiovascular events by a variety of mechanisms, including an increase in
      arterial stiffness by medial calcification or an increase in plaque vulnerability
      by a specific type of atherosclerotic calcification. Coronary calcification is a
      marker of atherosclerosis and evaluation of coronary artery calcium (CAC) score
      by cardiac MDCT has been recognized as the useful strategies to initiate or
      intensify appropriate treatment to slow the progression of atherosclerosis.
      Besides the risk of coronary heart disease, CAC has been demonstrated to be
      associated with the risk of complication during PCI, including arterial
      perforation and dissection, stent malapposition, and resultant late stent
      thrombosis. Increasing evidence demonstrates that both types of vascular
      calcification are active and tightly regulated by a process similar to bone
      formation.

PMID- 22133824
TI  - [Bone and calcium update; diagnosis and therapy of bone metabolism disease
      update. Regulatory Mechanism of Mammalian Sirtuin SIRT1 in Vascular
      calcification: impact of vascular smooth muscle cell senescence].
AB  - Vascular aging manifest several features, namely atherosis, sclerosis and
      calcified change. Vascular calcification makes the management of hemodynamics
      more difficult in the elderly, because ectopic calcium deposition in the
      vasculatures contributes to excessive blood pressure variability, isolated
      systolic hypertension with increased arterial wave reflectance, and subsequent
      ischemic cardiovascular (CV) events. Vascular calcification has been shown to
      result from passive precipitation of calcium with aging and osteoporosis.
      However, accumulating recent evidences have shown it to be attributable to an
      active'cell-mediated process'resembling osteogenesis in bone rather than passive
      mineral precipitation in vascular smooth muscle cells (SMC) . Cellular senescence
      has been recently shown to be linked to atherosclerogenesis ; however, few
      reports have addressed whether cellular senescence is associated with SMC
      calcification. Our new findings show that the senescent phenotypic change is
      associated with osteoblastic trans-differentiation in SMC and mammalian sirtuin
      SIRT1, which is well known as a longevity gene, can play an inhibitory role in
      the cellular senescence-related vascular calcification under hyperphosphatemia.
      In addition, the activation of Runx2, a potent osteogenic transcriptional factor,
      in SMC is regulated by SIRT1-p21 axis. The identification of therapeutic targets
      which can slow down the progression or even reverse the senescent phenotypic
      change in SMC could be an important step forward in the treatment of vascular
      calcification.

PMID- 22133825
TI  - [Bone and calcium update; diagnosis and therapy of bone metabolism disease
      update. Molecular mechanism in cardiac valve calcification].
AB  - When cardiac valve stenosis is accompanied by calcification, symptoms and
      prognosis become much worse and may cause sudden cardiac death. The prevalence of
      this disease has increased with the rapidly aging in Japanese society. It has
      recently been revealed that several genes which relate to physiological
      ossification and calcification play important roles in this process. To find a
      suitable target for medical treatment, the molecular mechanism for calcification
      of cardiac valves should be elucidated in detail. In this review, we summarize
      the current knowledge on the pathology and molecular mechanism for ectopic
      calcification of the cardiac valve.

PMID- 22133826
TI  - [Bone and calcium update; diagnosis and therapy of bone metabolism disease
      update. Clinical assessment of atherosclerosis in aorta].
AB  - The purpose of clinical assessment of atherosclerosis in aorta is to detect early
      lesions that are associated with a substantial risk of cardiovascular disease,
      such as stroke, aortic aneurysm and dissection, and to develop a treatment
      strategy for reduction of the cardiovascular risk. The pulse wave velocity (PWV)
      and pulse wave analysis (augmentation index : AI) can reveal atherosclerotic
      functional vascular abnormalities. On the contrary, plain X-rays, ultrasound
      examination, computed tomography (CT) , and magnetic resonance imaging (MRI) can
      be employed to easily assess the severity of atherosclerotic vascular damage
      morphologically. In these examinations, only PWV, as an index of arterial
      stiffness, can detect early atherosclerotic change in aorta before organic
      change. So, considering the importance of detecting early lesion, PWV is the most
      useful examination of atherosclerosis in aorta.

PMID- 22133827
TI  - [Bone and calcium update; bone research update. Role of steroid hormones in
      regulation of the epigenesis].
AB  - Fat-soluble ligands like steroid hormones exert their actions through nuclear
      receptor-mediated transcriptional controls. Nuclear receptors are hormone
      dependent transcription factors, and their ligand-dependent function is
      facilitated by transcriptional co-regulators, that were initially considered to
      bridge nuclear receptors with transcription initiation complex. However, recent
      progress in epigenome and chromatin research has uncovered that hormone-dependent
      transcriptional controls by nuclear receptors require a number of
      epigenetic/transcriptional co-regurators facilitating chromatin reorganization.

PMID- 22133828
TI  - [Bone and calcium update; bone research update. Trafficking of osteoclast
      precursors visualized by intravital imaging technology].
AB  - Osteoclasts are 'bone-resorbing' giant polykaryons that differentiate from
      mononuclear macrophage/monocyte-lineage hematopoietic precursors. However, it has
      remained unclear how osteoclast precursors migrate into the bone surface and what
      controls their migratory behaviors in vivo . To investigate these questions, we
      utilized an advanced imaging system for visualizing live bone tissues with
      intravital multiphoton microscopy that we have recently established. By means of
      the system we have recently succeeded in visualization of osteoclast precursors
      in live bones and revealed that sphingosine-1-phosphate (S1P) , a lipid mediator,
      dynamically regulates migration and localization of osteoclasts and their
      precursors in vivo . Here we show the latest data and the detailed methodology of
      intravital imaging of bone tissues, and also discuss its further application.

PMID- 22133829
TI  - [Bone and calcium update; bone research update. Osteoclastogenesis and
      osteoimmunology].
AB  - Bone is constantly renewed by the balanced action of osteoblastic bone formation
      and osteoclastic bone resorption. This restructuring process called "bone
      remodeling" is important not only for maintaining bone mass and strength, but
      also for mineral homeostasis. Excessive osteoclast activity leads to pathological
      bone resorption, as seen in a variety of local or generalized osteopenic
      conditions such as rheumatoid arthritis, cancer bone metastasis and osteoporosis.
      The immune and skeletal systems share various molecules including cytokines,
      signaling molecules, transcription factors and membrane receptors. The scope of
      osteoimmunology has been extended to encompass a wide range of molecular and
      cellular interactions, the elucidation of which will provide a scientific basis
      for future therapeutic approaches to diseases related to the immune and skeletal
      systems.

PMID- 22133830
TI  - [Bone and calcium update; bone research update. Regulatory mechanisms in
      osteoblast differentiation].
AB  - Differentiation process of osteoblasts, which play a central role in bone
      formation, is harmoniously controlled by several cytokines and hormones.
      Particularly, Bone Morphogenetic Protein (BMP) , Indian Hedgehog (Ihh) , and Wnt
      family proteins are important cytokines for osteoblast differentiation.
      Understandings of molecular mechanisms by which these cytokines stimulate
      osteoblast differentiation have been extensively investigated. BMP/Smad
      signaling, canonical Wnt pathway, non-canonical Wnt pathway and Ihh/Gli signaling
      play critical role in osteoblast differentiation. Furthermore, biochemical and
      genetic studies have demonstrated important roles of Runt related transcription
      factor 2 (Runx2) , Osterix, Activating transcription factor 4 (ATF4) , Msh
      homeobox 2 (Msx2) and Oasis for osteoblast differentiation. Thus, these milestone
      studies have dramatically progressed in our understanding of the cellular and
      molecular mechanisms of osteoblast differentiation for 20 years.

PMID- 22133831
TI  - [Bone and calcium update; bone research update. Molecular mechanisms regulating
      chondrocyte differentiation and hypertrophy].
AB  - Chondrocyte differentiation process is composed of multiple steps. During the
      process, hypertrophy of chondrocyte is controlled by various factors including
      Indian hedgehog (Ihh) and parathyroid hormone related peptide (PTHrP) . PTHrP
      signals regulate HDAC4-MEF2C axis in chondrocyte. Recently, several co-factors
      have been found to interact with Sox9. Function of chondrocyte-specific microRNA
      has been determined. Several types of Cre transgenic mice are available to
      express Cre at various steps during chondrocyte differentiation. Using these
      mice, gene functions at specific steps of chondrocyte differentiation are
      analyzed by generating conditional knockout mice and conditional transgenic mice.
      It may be possible in future to induce chondrocytes from skin fibroblasts of
      patients with genetic cartilage diseases by using iPS cell technology, and to
      analyze molecular mechanism that control differentiation of human chondrocytes.

PMID- 22133832
TI  - [Bone and calcium update; diagnosis and therapy of metabolic bone disease update.
      Guideline for prevention and treatment of osteoporosis update].
AB  - The outline of Japanese Guideline for the prevention and treatment of
      Osteoporosis (up dated 2011) was introduced.  Descriptions were made on the
      identification of risk factors for fracture, prevention of osteoporosis, criteria
      for initiating pharmacotherapy to prevent fracture. Grading of recommendation for
      medication based on evidence, introduction of bone turnover markers in the
      treatment and secondary osteoporosis.

PMID- 22133833
TI  - [Bone and calcium update; diagnosis and therapy of metabolic bone disease update.
      Advances in clinical trials for osteoporosis in Japan].
AB  - Microdensitometry of the metacarpal bone on radiograph was first set up as the
      endpoint of the treatment in clinical trials in Japan in 1980s. Then, radial bone
      mineral content obtained by single photon absorptiometry was used. In 1990s,
      lumbar spine BMD measured by DXA became the major endpoint of the study which was
      designed as prospective, randomized, double-blind, controlled trial. In 2000s,
      assessments on the incidences of the vertebral fractures have become mandatory as
      the primary endpoint of the placebo-controlled trial. The numbers of the subjects
      required in the study are getting larger and the subtleties in the study
      including adverse events more important along the progress of evidence-based
      medicine.

PMID- 22133834
TI  - [Bone and calcium update; diagnosis and therapy of metabolic bone disease update.
      Progress in X-ray analysis of bone].
AB  - In the past several decades, the method of bone mineral measurement has been
      establised and contributed to the advancement of clinical practice of
      osteoporosis. The microfocus X-ray CT has been applied to the analysis of bome
      microarchitecture, and recently it is possible to analyse trabecular architecture
      in distal radius using clinical CT. On the other hand, as to the aplication of
      plain radiography, standarization of vertebral fracture assessment has been
      progressed in parallel to the recognition of prevalent vertebral fracture as
      fracture risk.

PMID- 22133835
TI  - [Bone and calcium update; diagnosis and therapy of metabolic bone disease update.
      Advances in treatment of CKD-MBD].
AB  - Secondary hyperparathyroidism and vascular calcification are major clinical
      states in CKD-MBD (chronic kidney disease-mineral and bone disorder) . Recently
      fibroblast growth factor 23-klotho axis has been shown to be implicated in the
      pathogenesis of secondary hyperparathyroidism. Vascular calcification has been
      identified to be a highly regulated process. Novel therapeutic agents for CKD-MBD
      have been developed. The guidelines of CKD-MBD have been announced from many
      countries including Japan from the point of view of patient's survival, and it is
      expected that the development of practice for CKD-MBD will contribute to better
      survival.

PMID- 22133836
TI  - [Calcium pros and cons significance and risk of phosphorus supplementation. The
      necessity of phosphorus supplementation for hypophosphatemia].
AB  - Phosphate plays a vital role forming the high-energy band within ATP. The
      pathophysiological results of phosphate deficiency are inadequate supplies of
      energy-rich phosphates and, in particular, inhibition of glyceraldehyde-3-
      phosphate dehydrogenase, which occupies a key position in glycolysis. The effect
      of this on the central nervous system, muscle and erythrocyte energy metabolism
      is to reduce ATP and 2,3-diphosphoglycerate levels, leading to left-hand
      displacement of the oxygen-hemoglobin dissociation curve with decreased
      peripheral oxygen uptake and transport. Therefore, detection and treatment of
      acute hypophosphatemia is important in many hospitalized patients particularly in
      ICU patients. Severe hypophosphatemia is also associated with a number of
      neuromuscular and cardiovascular sequelae, in which phosphate supplementation
      leads to improved symptoms and clinical parameters. In clinical practice it is
      common on administering 0.4 mmol (12 mg) phosphate/kg per day, and to adjust this
      on the basis of the serum phosphate analysis.

PMID- 22133837
TI  - [Calcium pros and cons significance and risk of phosphorus supplementation. The
      risk of dietary phosphorus intake].
AB  - Dietary intake of phosphorus (Pi) is an important determinant of Pi balance in
      patients who have chronic kidney disease (CKD) and a reduced GFR. High dietary Pi
      burden may promote vascular calcification and cardiovascular events. Recently,
      Ohnishi and Razzaque suggest that phosphate toxicity accelerates the mammalian
      aging process and that reducing the phosphate burden can delay the aging (FASEB J
      24, 3562, 2010) . Dietary Pi is derived largely from foods with high protein
      content or food additives. Accurate information on the Pi content of foods is
      needed to achieve a low Pi intake and effectively manage CKD and the aging. In
      this review, we discuss the risk of dietary Pi intake in CKD and the aging.

PMID- 22133838
TI  - Biological treatment options for cyanobacteria metabolite removal--a review.
AB  - The treatment of cyanobacterial metabolites can consume many resources for water
      authorities which can be problematic especially with the recent shift away from
      chemical- and energy-intensive processes towards carbon and climate neutrality.
      In recent times, there has been a renaissance in biological treatment, in
      particular, biological filtration processes, for cyanobacteria metabolite
      removal. This in part, is due to the advances in molecular microbiology which has
      assisted in further understanding the biodegradation processes of specific
      cyanobacteria metabolites. However, there is currently no concise portfolio which
      captures all the pertinent information for the biological treatment of a range of
      cyanobacterial metabolites. This review encapsulates all the relevant information
      to date in one document and provides insights into how biological treatment
      options can be implemented in treatment plants for optimum cyanobacterial
      metabolite removal.

PMID- 22133839
TI  - Bench-scale study of active mine water treatment using cement kiln dust (CKD) as
      a neutralization agent.
AB  - The overall objective of this study was to investigate the potential impact on
      settled water quality of using cement kiln dust (CKD), a waste by-product, to
      replace quicklime in the active treatment of acidic mine water. Bench-scale
      experiments were conducted to evaluate the treatment performance of calcium
      hydroxide (Ca(OH)(2)) slurries generated using four different CKD samples
      compared to a control treatment with quicklime (CaO) in terms of reducing acidity
      and metals concentrations in acid mine drainage (AMD) samples taken from the
      effluent of a lead/zinc mine in Atlantic Canada. Results of the study showed that
      all of the CKD samples evaluated were capable of achieving greater than 97%
      removal of total zinc and iron. The amount of solid alkaline material required to
      achieve pH targets required for neutralization of the AMD was found to be higher
      for treatment with the CKD slurries compared to the quicklime slurry control
      experiments, and varied linearly with the free lime content of the CKD. The
      results of this study also showed that a potential benefit of treating mine water
      with CKD could be reduced settled sludge volumes generated in the active
      treatment process, and further research into the characteristics of the sludge
      generated from the use of CKD-generated calcium hydroxide slurries is
      recommended.

PMID- 22133840
TI  - Equilibrium and intra-particle diffusion of stabilized landfill leachate onto
      micro- and meso-porous activated carbon.
AB  - Stabilized landfill leachate has previously been treated with activated carbon
      (AC); however, information on the selectivity of AC depending upon the pore size
      is minimal. Isotherm and kinetic experiments were conducted using three
      commercially available AC products, one micro-porous and two meso-porous.
      Equilibrium adsorption and intra-particle diffusion of organic matter from
      stabilized leachate was studied. Isotherm experimental data were fitted to
      Langmuir, Freundlich, and Redlich-Peterson isotherm models in non-linear forms.
      Of the three isotherm models, the Redlich-Peterson model provided the best fit to
      the experimental data and showed a similar organic matter adsorption capacity
      (approximately 0.2 g total organic carbon (TOC) g(-1) AC) for both micro-porous
      and meso-porous AC. The organic matter effective intra-particle diffusion
      coefficients (D(e)) in both AC types were on the order of 10(-10) m(2) s(-1) for
      AC particle sizes greater than 0.5 mm. Meso-porous ACs showed slightly higher
      D(e) compared to micro-porous AC. Rapid small-scale tests showed a maximum of 80%
      TOC removal from leachate by each AC investigated. Fluorescence spectroscopy
      showed a preferential adsorption of fulvic-type organic matter with an increase
      in empty bed contact time by each AC.

PMID- 22133841
TI  - Voltage-gated calcium channels and Parkinson's disease.
AB  - A complex interaction of environmental, genetic and epigenetic factors combine
      with ageing to cause the most prevalent of movement disorders Parkinson's
      disease. Current pharmacological treatments only tackle the symptoms and do not
      stop progression of the disease or reverse the neurodegenerative process. While
      some incidences of Parkinson's disease arise through heritable genetic defects,
      the cause of the majority of cases remains unknown. Likewise, why some neuronal
      populations are more susceptible to neurodegeneration than others is not clear,
      but as the molecular pathways responsible for the process of cell death are
      unravelled, it is increasingly apparent that disrupted cellular energy metabolism
      plays a central role. Precise control of cellular calcium concentrations is
      crucial for maintenance of energy homeostasis. Recently, differential cellular
      expression of neuronal voltage-gated calcium channel (Ca(V)) isoforms has been
      implicated in the susceptibility of vulnerable neurons to neurodegeneration in
      Parkinson's disease. Ca(V) channels are also involved in the synaptic plasticity
      response to the denervation that occurs in Parkinson's disease and following
      chronic treatment with anti-parkinsonian drugs. This review will examine the
      putative role neuronal Ca(V) channels have in the pathogenesis and treatment of
      Parkinson's disease.

PMID- 22133842
TI  - The PSD-95/nNOS complex: new drugs for depression?
AB  - Drug treatment of major depressive disorder is currently limited to the use of
      agents which influence monoaminergic neuronal transmission including inhibitors
      of presynaptic transporters and monoamine oxidase. Typically improvement in
      depressive symptoms only emerges after several weeks of treatment, suggesting
      that downstream neuronal adaptations rather than the elevation in synaptic
      monoamine levels are responsible for antidepressant effects. In recent years, the
      NMDA receptor has emerged as a promising target for treating CNS disorders
      including stroke, pain and depression. In this review, we outline the molecular
      mechanisms underlying NMDA receptor signalling in neurons and in particular
      provide an overview of the role of the NMDAR/PSD-95/nNOS complex in CNS
      disorders. We discuss novel drug developments made that suggest the NMDAR/PSD
      95/nNOS complex as a potential target for the treatment of depression. The review
      also provides examples of how PDZ-based protein-protein interactions can be
      exploited as novel drug targets for disease.

PMID- 22133843
TI  - Role of ranolazine in angina, heart failure, arrhythmias, and diabetes.
AB  - Ranolazine which is currently approved as an antianginal agent reduces the Na
      dependent Ca overload via inhibition of the late sodium current (late I(Na)) and
      thus improves diastolic tone and oxygen handling during myocardial ischemia.
      According to accumulating evidence ranolazine also exerts beneficial effects on
      diastolic and systolic heart failure where late I(Na) was also found to be
      elevated. Moreover, late I(Na) plays a crucial role as an arrhythmic substrate.
      Ranolazine has been described to have antiarrhythmic effects on ventricular as
      well as atrial arrhythmias without any proarrythmia or severe organ toxicity as
      it is common for several antiarrhythmic drugs. In patients with diabetes,
      treatment with ranolazine led to a significant improvement of glycemic control.
      In this article possible new clinical indications of the late I(Na)-inhibitor
      ranolazine are reviewed. We summarize novel experimental and clinical studies and
      discuss the significance of the available data.

PMID- 22133845
TI  - Evidence, lack of evidence, controversy, and debate in the provision and
      performance of the surgery of acute type A aortic dissection.
AB  - Acute type A aortic dissection is a lethal condition requiring emergency surgery.
      It has diverse presentations, and the diagnosis can be missed or delayed. Once
      diagnosed, decisions with regard to initial management, transfer, appropriateness
      of surgery, timing of operation, and intervention for malperfusion complications
      are necessary. The goals of surgery are to save life by prevention of pericardial
      tamponade or intra-pericardial aortic rupture, to resect the primary entry tear,
      to correct or prevent any malperfusion and aortic valve regurgitation, and if
      possible to prevent late dissection-related complications in the proximal and
      downstream aorta. No randomized trials of treatment or techniques have ever been
      performed, and novel therapies-particularly with regard to extent of surgery-are
      being devised and implemented, but their role needs to be defined. Overall,
      except in highly specialized centers, surgical outcomes might be static, and
      there is abundant room for improvement. By highlighting difficulties and
      controversies in diagnosis, patient selection, and surgical therapy, our over
      arching goal should be to enfranchise more patients for treatment and improve
      surgical outcomes.

PMID- 22133844
TI  - Correlation of levels of neuronal and glial markers with radiological measures of
      infarct volume in ischaemic stroke: a systematic review.
AB  - BACKGROUND: A blood test that quantified the extent of brain damage following
      ischaemic stroke might be a useful surrogate outcome measure in trials of acute
      stroke treatments. Measures of neuronal and glial damage, such as neuron-specific
      enolase (NSE), glial fibrillary acidic protein, tau-protein, myelin-basic protein
      and S100-beta are potential candidate biomarkers. AIM: We systematically reviewed
      the relevant literature to find studies that correlated blood levels of neuronal
      and glial damage markers with imaging measures of infarct volume. METHODS: We
      identified studies with a comprehensive search of databases and the reference
      lists of relevant studies. We included studies that: (1) measured the highest
      level, or area under the curve (AUC) over time of markers of cerebral damage, (2)
      calculated infarct volume, and (3) correlated the two measures. RESULTS:
      Seventeen studies met the criteria for the systematic review. There were
      sufficient data to provide summary estimates for S100-beta and NSE. The peak
      level and AUC over time of both markers correlated with subacute infarct volume.
      Measurements of S100-beta later than 24 h after stroke were better correlated
      with subacute infarct size than earlier measurements. However, scan times varied,
      and none was later than 8 days after stroke. CONCLUSION: Peak and AUC levels of
      NSE and S100-beta levels correlated with subacute infarct volume. Correlations of
      S100-beta with infarct volume were stronger when measured after 24 h than closer
      to admission. Exploratory studies within clinical trials are necessary before
      blood markers of cerebral tissue damage can be recommended as surrogate
      endpoints.

PMID- 22133846
TI  - Percutaneous transvenous Melody valve-in-ring procedure for mitral valve
      replacement.
AB  - OBJECTIVES: The purpose of this study was to demonstrate the feasibility of
      percutaneous transvenous mitral valve-in-ring (VIR) implantation using the Melody
      valve in an ovine model. BACKGROUND: The recurrence of mitral regurgitation
      following surgical mitral valve (MV) repair in both adult and pediatric patients
      remains a significant clinical problem. Mitral annuloplasty rings are commonly
      used in MV repair procedures and may serve as secure landing zones for
      percutaneous valves. METHODS: Five sheep underwent surgical MV annuloplasty (24
      mm, n = 2; 26 mm, n = 2; 28 mm, n = 1). Animals underwent cardiac catheterization
      with VIR implantation via a transfemoral venous, transatrial septal approach 1
      week following surgery. Hemodynamic, angiographic, and echocardiographic data
      were recorded before and after VIR. RESULTS: VIR was technically successful and
      required <1 h of procedure time in all animals. Fluoroscopy demonstrated securely
      positioned Melody valves within the annuloplasty ring in all animals. Angiography
      revealed no significant MV regurgitation in 4 and moderate central MV
      regurgitation in the animal with the 28-mm annuloplasty. All animals demonstrated
      vigorous left ventricular function, no outflow tract obstruction, and no aortic
      valve insufficiency. CONCLUSIONS: This study demonstrated the feasibility of a
      purely percutaneous approach to MV replacement in patients with preexisting
      annuloplasty rings. This novel approach may be of particular benefit to patients
      with failed repair of ischemic mitral regurgitation and in pediatric patients
      with complex structural heart disease.

PMID- 22133847
TI  - Carriers of lecithin cholesterol acyltransferase gene mutations have accelerated
      atherogenesis as assessed by carotid 3.0-T magnetic resonance imaging
      [corrected].
AB  - OBJECTIVES: The aim of this study was to investigate the role of reduced
      lecithin: cholesterol acyltransferase (LCAT) function on atherogenesis using 3.0
      T carotid magnetic resonance imaging (MRI) and B-mode ultrasound. BACKGROUND: The
      role of low high-density lipoprotein cholesterol as a causal factor in
      atherogenesis has recently been questioned. LCAT plays a key role in high-density
      lipoprotein cholesterol metabolism. METHODS: Carotid 3.0-T MRI and B-mode
      ultrasound measurements were performed in 40 carriers of LCAT gene mutations and
      40 controls, matched for age. Patients with cardiovascular disease were excluded.
      RESULTS: Carriers had 31% lower LCAT activity levels and 38% decreased high
      density lipoprotein cholesterol levels (both p < 0.001 vs. controls). Carriers
      presented with a 10% higher normalized wall index (0.34 +/- 0.07 vs. 0.31 +/-
      0.04, p = 0.002), a 22% higher mean wall area (17.3 +/- 8.5 mm(2) vs. 14.2 +/-
      4.1 mm(2), p = 0.01), and a 22% higher total wall volume (1,039 +/- 508 mm(3) vs.
      851 +/- 247 mm(3), p = 0.01 vs. controls) as measured by MRI. The prevalence (20
      vs. 5, p = 0.002) and the total volume (102 mm(3) vs. 3 mm(3)) of atherosclerotic
      plaque components on MRI relating to lipid-rich tissue or calcification were also
      higher in carriers than in controls. All differences retained significance after
      adjustment for age, sex, blood pressure, low-density lipoprotein cholesterol,
      body mass index, smoking, and family history of cardiovascular disease. Common
      carotid intima-media thickness measured with ultrasound was increased in carriers
      by 12.5% (0.72 +/- 0.33 mm vs. 0.64 +/- 0.15 mm, p = 0.14). CONCLUSIONS: Carriers
      of LCAT gene mutations exhibit increased carotid atherosclerosis, indicating an
      increased risk of cardiovascular disease. The present findings imply that
      increasing LCAT activity may be an attractive target in cardiovascular prevention
      strategies.

PMID- 22133848
TI  - Low levels of high-density lipoprotein cholesterol due to lecithin:cholesterol
      acyltransferase mutations increase carotid atherosclerosis.

PMID- 22133849
TI  - Septal involvement in patients with post-infarction ventricular tachycardia:
      implications for mapping and radiofrequency ablation.
AB  - OBJECTIVES: The purpose of this study was to assess the prevalence of the re
      entry circuit within the interventricular septum in post-infarction patients
      referred for ventricular tachycardia (VT) ablation. BACKGROUND: Post-infarction
      ventricular tachycardia can involve the endocardial myocardium, the intramural
      myocardium, the epicardium, or the His Purkinje system. METHODS: Among 74
      consecutive patients with recurrent post-infarction VT, 33 patients (45%) were
      identified in whom the critical part of the VT involved the interventricular
      septum. A total of 206 VTs were induced in these 33 patients. In 46 of the 206
      VTs, a critical component was identified in the interventricular septum. The
      critical isthmus of the re-entry circuit was identified by entrainment mapping,
      activation mapping, or pace-mapping. RESULTS: In 32 of 46 VTs (70%), the critical
      component of the re-entry circuit was confined to the endocardium. In 9 of 46 VTs
      (20%), the critical component involved the Purkinje system, and in 5 of 46 VTs
      (11%), an intramural area was critical. Entrainment and/or pace-mapping helped to
      identify critical areas of endocardial VTs as well as VTs involving the Purkinje
      fibers, but neither of these mapping techniques localized intramural VTs.
      Electrocardiographic characteristics were specific for each of the septal
      locations. All VTs mapped to the interventricular septum were acutely
      successfully ablated. VTs recurred in 9 of 33 patients with septal VTs during a
      mean follow-up period of 40 +/- 20 months. CONCLUSIONS: Post-infarction VT
      involving the interventricular septum can involve the endocardial muscle,
      Purkinje fibers, or intramural muscle fibers. Electrocardiographic
      characteristics differ depending on the type of tissue involved.

PMID- 22133850
TI  - Percutaneous radiofrequency septal reduction for hypertrophic obstructive
      cardiomyopathy in children.
AB  - OBJECTIVES: The aim of this study was to assess the efficacy of radiofrequency
      catheter ablation (RFCA) in the treatment of hypertrophic obstructive
      cardiomyopathy in children. BACKGROUND: Hypertrophic obstructive cardiomyopathy
      is an uncommon cause of left ventricular outflow tract obstruction in children.
      In symptomatic patients, open heart surgical myectomy has hitherto been the only
      therapeutic option. METHODS: In 32 children, at a median age of 11.1 (range 2.9
      to 17.5) years and weight of 31 (15 to 68) kg, ablation of the hypertrophied
      septum was performed using a cool-tip ablation catheter via a femoral arterial
      approach. The median number of lesions was 27 (10 to 63) and fluoroscopic time
      was 24 (12 to 60) min. RESULTS: The majority of patients demonstrated an
      immediate decrease in the catheter pullback gradient (mean 78.5 +/- 26.2 mm Hg
      pre-RFCA versus mean 36.1 +/- 16.5 mm Hg post-RFCA, p < 0.01) and a further
      reduction in the Doppler echocardiographic gradient (mean 96.9 +/- 27.0 mm Hg pre
      RFCA versus 32.7 +/- 27.1 mm Hg post-RFCA, p < 0.01) at follow-up. One patient
      died due to a paradoxical increase in left ventricular outflow tract obstruction,
      and another had persistent atrioventricular block that required permanent pacing.
      Six patients required further procedures (surgery, pacing, or further RFCA)
      during a median follow-up of 48 (3 to 144) months. CONCLUSIONS: The preliminary
      results of RFCA for septal reduction in children with hypertrophic cardiomyopathy
      are promising and merit further evaluation.

PMID- 22133851
TI  - Progressive right ventricular dysfunction in patients with pulmonary arterial
      hypertension responding to therapy.
AB  - OBJECTIVES: The purpose of this study was to examine the relationship between
      changes in pulmonary vascular resistance (PVR) and right ventricular ejection
      fraction (RVEF) and survival in patients with pulmonary arterial hypertension
      (PAH) under PAH-targeted therapies. BACKGROUND: Despite the fact that medical
      therapies reduce PVR, the prognosis of patients with PAH is still poor. The
      primary cause of death is right ventricular (RV) failure. One possible
      explanation for this apparent paradox is the fact that a reduction in PVR is not
      automatically followed by an improvement in RV function. METHODS: A cohort of 110
      patients with incident PAH underwent baseline right heart catheterization,
      cardiac magnetic resonance imaging, and 6-min walk testing. These measurements
      were repeated in 76 patients after 12 months of therapy. RESULTS: Two patients
      underwent lung transplantation, 13 patients died during the first year, and 17
      patients died in the subsequent follow-up of 47 months. Baseline RVEF (hazard
      ratio [HR]: 0.938; p = 0.001) and PVR (HR: 1.001; p = 0.031) were predictors of
      mortality. During the first 12 months, changes in PVR were moderately correlated
      with changes in RVEF (R = 0.330; p = 0.005). Changes in RVEF (HR: 0.929; p =
      0.014) were associated with survival, but changes in PVR (HR: 1.000; p = 0.820)
      were not. In 68% of patients, PVR decreased after medical therapy. Twenty-five
      percent of those patients with decreased PVR showed a deterioration of RV
      function and had a poor prognosis. CONCLUSIONS: After PAH-targeted therapy, RV
      function can deteriorate despite a reduction in PVR. Loss of RV function is
      associated with a poor outcome, irrespective of any changes in PVR.

PMID- 22133852
TI  - Predicting long-term survival in pulmonary arterial hypertension: more than just
      pulmonary vascular resistance.

PMID- 22133854
TI  - Improved risk assessment for abdominal aortic aneurysm rupture: off-the-wall
      imaging.

PMID- 22133853
TI  - In vivo characterization of a new abdominal aortic aneurysm mouse model with
      conventional and molecular magnetic resonance imaging.
AB  - OBJECTIVES: The goal of this study was to use noninvasive conventional and
      molecular magnetic resonance imaging (MRI) to detect and characterize abdominal
      aortic aneurysms (AAAs) in vivo. BACKGROUND: Collagen is an essential constituent
      of aneurysms. Noninvasive MRI of collagen may represent an opportunity to help
      detect and better characterize AAAs and initiate intervention. METHODS: We used
      an AAA C57BL/6 mouse model in which a combination of angiotensin II infusion and
      transforming growth factor-beta neutralization results in AAA formation with
      incidence of aortic rupture. High-resolution, multisequence MRI was performed to
      characterize the temporal progression of an AAA. To allow molecular MRI of
      collagen, paramagnetic/fluorescent micellar nanoparticles functionalized with a
      collagen-binding protein (CNA-35) were intravenously administered. In vivo
      imaging results were corroborated with immunohistochemistry and confocal
      fluorescence microscopy. RESULTS: High-resolution, multisequence MRI allowed the
      visualization of the primary fibrotic response in the aortic wall. As the
      aneurysm progressed, the formation of a secondary channel or dissection was
      detected. Further analysis revealed a dramatic increase of the aortic diameter.
      Injection of CNA-35 micelles resulted in a significantly higher magnetic
      resonance signal enhancement in the aneurysmal wall compared with nonspecific
      micelles. Histological studies revealed the presence of collagen in regions of
      magnetic resonance signal enhancement, and confocal microscopy proved the precise
      co-localization of CNA-35 micelles with type I collagen. In addition, in a proof
      of-concept experiment, we reported the potential of CNA-35 micelles to
      discriminate between stable AAA lesions and aneurysms that were likely to rapidly
      progress or rupture. CONCLUSIONS: High-resolution, multisequence MRI allowed
      longitudinal monitoring of AAA progression while the presence of collagen was
      visualized by nanoparticle-enhanced MRI.

PMID- 22133855
TI  - Rupture of a saphenous graft into the right ventricle.

PMID- 22133856
TI  - President's page: Wrinkling the soul.

PMID- 22133857
TI  - Distal aortic and peripheral arterial aneurysms in patients with Marfan syndrome.

PMID- 22133858
TI  - Cerebrovascular atherosclerosis and stroke in patients after coronary artery
      bypass graft surgery.

PMID- 22133860
TI  - Impaired fasting glucose and the risk of incident diabetes mellitus and
      cardiovascular events.

PMID- 22133861
TI  - Determinants of exercise intolerance in heart failure with preserved ejection
      fraction.

PMID- 22133864
TI  - A worrisome interventricular septum: more than meets the eye.

PMID- 22133865
TI  - T-bet employs diverse regulatory mechanisms to repress transcription.
AB  - Lineage-defining transcription factors are responsible for activating the
      signature genes required for a given cell fate. They are also needed to repress
      the genetic programs associated with alternative lineage decisions. The T-box
      transcription factor T-bet is required for CD4(+) T helper 1 (Th1) cell
      differentiation. Numerous studies have explored the mechanisms by which T-bet
      activates the Th1 gene profile, but until recently not much was known about the
      mechanisms that T-bet utilizes to negatively regulate alternative T helper cell
      differentiation pathways such as the Th2 and Th17 fates. Here, we discuss new
      advances in the field that highlight the diverse mechanisms that T-bet employs to
      antagonize the gene programs for alternative T helper cell fates.

PMID- 22133866
TI  - A new diagnostic scoring for discrimination of tuberculous and bacterial
      meningitis on the basis of clinical and laboratory findings.
AB  - OBJECTIVES: The aim of this study was to develop a new diagnostic index (DI) on
      the basis of clinical and laboratory findings including serum C-reactive protein
      (CRP) for tuberculous meningitis (TM) and bacterial meningitis (BM). SUBJECTS AND
      METHODS: During a 7-year period, 96 adult patients with meningitis (30 with TM
      and 66 with BM) were studied retrospectively. Multivariate logistic regression
      analysis was performed to investigate the diagnostic value of clinical and
      laboratory parameters as independent predictors on discrimination of tuberculous
      from BM patients. RESULTS: Six features predictive for diagnosis including age,
      CSF leukocyte count, PML dominance, length of illness, serum CRP level and blood
      WBC count were used. The DI model developed from these features had very high
      sensitivity and specificity rates of 100.0 and 95.4%, respectively. The
      sensitivity and specificity rates were 97.4 and 100%, respectively, in
      microbiologically proven cases. CONCLUSION: Our results suggested that this new
      DI which consists of simple clinical and laboratory parameters had the power to
      discriminate adult patients with documented tuberculous and BM (excluding
      Brucella meningitis). It should, however, be tested in prospective studies.

PMID- 22133867
TI  - Proximal tibial bone graft: the volume of cancellous bone, and strength of
      decancellated tibias by the medial approach.
AB  - This study aimed to assess the volume of cancellous bone harvested by the medial
      approach from proximal tibia and compare the maximal compressive strength of
      decancellated tibias with intact tibias. Twelve cadavers were studied (11 male; 1
      female). Cadavers with a history of bone disease and female cadavers over 60
      years of age were excluded. Cancellous bone was taken from the right proximal
      tibia by the medial approach. Non-compressed and compressed cancellous bone
      volume was measured. Maximal compressive strength of decancellated tibias and
      intact tibias was measured and compared. The mean volume of bone harvested was
      14.58+/-3.30 ml with the non-compress technique (range 10.5-19.5 ml) and 6.62+/
      1.60 ml (range 4.0-9.2 ml) with the compress technique. There was no significant
      difference between the maximal compressive strength of the decancellated tibias
      and the intact tibias (P=0.085). Sufficient volume of cancellous bone for bone
      grafting in the oral maxillofacial surgery region can be harvested from the
      proximal tibia by the medial approach. The strength of decancellated tibias and
      intact tibias after harvesting cancellous bone graft were not different.

PMID- 22133868
TI  - Dendritic cells in experimental renal inflammation--Part I.
AB  - Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting
      cells that act as master regulators of acquired and innate immune responses.
      While descriptions of cells with dendritic morphology in rodent kidneys date back
      to the early 1970s, a network of DCs in the mouse kidney has only recently been
      described. DCs acquire distinct phenotypic and functional characteristics
      depending on the microenvironment and the disease stages. Concomitantly, their
      communication with cells of the adaptive immunity might have tissue-protective or
      tissue-deleterious consequences. This review summarizes results from recent
      studies on the role of DCs in experimental renal inflammation.

PMID- 22133869
TI  - Dendritic cells in human renal inflammation--Part II.
AB  - Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting
      cells that act as master regulators of acquired and innate immune responses.
      Here, we review the available information on their role in human renal
      inflammation. In the 1980s and early 1990s, major histocompatibility complex
      class II antigen- (HLA-DR) positive DCs were first described in normal human
      kidneys and in the interstitium of kidneys from patients with glomerulonephritis.
      Several DC subtypes were subsequently distinguished based on their expression of
      CD1c/BDCA-1, CD141/BDCA-3 and CD209/DC-SIGN (in combination with HLA-DR). These
      cells were almost exclusively found in the tubulointerstitium, with increased
      numbers seen during glomerulonephritis. It appears that the human renal
      tubulointerstitium harbors different DC types which allow the collection of both
      exogenous as well as endogenous antigens. Plasmacytoid DCs have a plasma cell
      like morphology and were commonly found within nodular tubulointerstitial
      infiltrates. Follicular DCs are rarely seen, but show a predominant localization
      in organized infiltrates. CD207/langerin is a marker for Langerhans cells.
      Langerin-positive cells have been found in association with the collecting ducts
      and urothelium. A functional characterization of these subtypes has been hampered
      by the difficulty of obtaining samples for analysis. However, these studies are
      clearly required to define the role of DCs and DC subsets in the pathophysiology
      of renal disease.

PMID- 22133870
TI  - Predictors and outcomes of lateral release in total knee arthroplasty: a cohort
      study of 1859 knees.
AB  - The use of lateral retinacular release (LR) to improve patellar tracking during
      total knee arthroplasty (TKR) remains contentious. This cohort study explored
      which pre-operative factors predicted LR, and analysed the effect of LR on short
      term complications and long term outcomes. One thousand eight hundred fifty-nine
      TKR patients were followed up for a mean of 5.49 years. One hundred fifty-four
      (8.3%) underwent LR. After regression analysis only, valgus deformity, year of
      surgery, maximal flexion and the operative surgeon predicted LR. LR patients
      stayed longer in hospital (10.8 vs 8.6 days) and had higher transfusion rates
      (20.3% vs 10.1%) than non-LR patients, but patellar fracture and infection rates
      were the same. Range of motion was poorer in the LR patients, but AKS Knee and
      functional scores were unaffected long term.

PMID- 22133871
TI  - Chain length-specific properties of ceramides.
AB  - Ceramides are a class of sphingolipids that are abundant in cell membranes. They
      are important structural components of the membrane but can also act as second
      messengers in various signaling pathways. Until recently, ceramides and
      dihydroceramides were considered as a single functional class of lipids and no
      distinction was made between molecules with different chain lengths. However,
      based on the development of high-throughput, structure-specific and quantitative
      analytical methods to measure ceramides, it has now become clear that in cellular
      systems the amounts of ceramides differ with respect to their chain length.
      Further studies have indicated that some functions of ceramides are chain-length
      dependent. In this review, we discuss the chain length-specific differences of
      ceramides including their pathological impact on Alzheimer's disease,
      inflammation, autophagy, apoptosis and cancer.

PMID- 22133872
TI  - Object interest in autism spectrum disorder: a treatment comparison.
AB  - A randomized control trial comparing two social communication treatments for
      children with autism spectrum disorder examined the effect of treatment on object
      interest. Thirty-two children, 18-60 months, were randomly assigned to the
      Picture Exchange Communication System (PECS) or Responsive Education and
      Prelinguistic Milieu Teaching (RPMT) condition. Assessment of object interest was
      conducted in an unstructured play session with different toys, activities, adult,
      and location than experienced in treatment. Results indicated children in the
      RPMT condition showed greater increases in object interest as compared to
      children in the PECS condition. Because child characteristics such as interest in
      objects may influence response to interventions using object play as contexts for
      treatment, it is important to improve our understanding of whether intervention
      can affect object interest.

PMID- 22133873
TI  - The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus
      macaques against active tuberculosis and reactivation of latent Mycobacterium
      tuberculosis infection.
AB  - It is estimated that one-third of the world's population is infected with
      Mycobacterium tuberculosis. Infection typically remains latent, but it can
      reactivate to cause clinical disease. The only vaccine, Mycobacterium bovis
      bacillus Calmette-Guerin (BCG), is largely ineffective, and ways to enhance its
      efficacy are being developed. Of note, the candidate booster vaccines currently
      under clinical development have been designed to improve BCG efficacy but not
      prevent reactivation of latent infection. Here, we demonstrate that administering
      a multistage vaccine that we term H56 in the adjuvant IC31 as a boost to
      vaccination with BCG delays and reduces clinical disease in cynomolgus macaques
      challenged with M. tuberculosis and prevents reactivation of latent infection.
      H56 contains Ag85B and ESAT-6, which are two of the M. tuberculosis antigens
      secreted in the acute phase of infection, and the nutrient stress-induced antigen
      Rv2660c. Boosting with H56/IC31 resulted in efficient containment of M.
      tuberculosis infection and reduced rates of clinical disease, as measured by
      clinical parameters, inflammatory markers, and improved survival of the animals
      compared with BCG alone. Boosted animals showed reduced pulmonary pathology and
      extrapulmonary dissemination, and protection correlated with a strong recall
      response against ESAT-6 and Rv2660c. Importantly, BCG/H56-vaccinated monkeys did
      not reactivate latent infection after treatment with anti-TNF antibody. Our
      results indicate that H56/IC31 boosting is able to control late-stage infection
      with M. tuberculosis and contain latent tuberculosis, providing a rationale for
      the clinical development of H56.

PMID- 22133874
TI  - Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse
      lymphomagenesis.
AB  - DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for
      methylation of cytosine residues in mammals. DNA methylation contributes to the
      epigenetic control of gene transcription and is deregulated in virtually all
      human tumors. To better understand the generation of cancer-specific methylation
      patterns, we genetically inactivated Dnmt3b in a mouse model of MYC-induced
      lymphomagenesis. Ablation of Dnmt3b function using a conditional knockout in T
      cells accelerated lymphomagenesis by increasing cellular proliferation, which
      suggests that Dnmt3b functions as a tumor suppressor. Global methylation
      profiling revealed numerous gene promoters as potential targets of Dnmt3b
      activity, the majority of which were demethylated in Dnmt3b-/- lymphomas, but not
      in Dnmt3b-/- pretumor thymocytes, implicating Dnmt3b in maintenance of cytosine
      methylation in cancer. Functional analysis identified the gene Gm128 (which we
      termed herein methylated in normal thymocytes [Ment]) as a target of Dnmt3b
      activity. We found that Ment was gradually demethylated and overexpressed during
      tumor progression in Dnmt3b-/- lymphomas. Similarly, MENT was overexpressed in
      67% of human lymphomas, and its transcription inversely correlated with
      methylation and levels of DNMT3B. Importantly, knockdown of Ment inhibited growth
      of mouse and human cells, whereas overexpression of Ment provided Dnmt3b+/+ cells
      with a proliferative advantage. Our findings identify Ment as an enhancer of
      lymphomagenesis that contributes to the tumor suppressor function of Dnmt3b and
      suggest it could be a potential target for anticancer therapies.

PMID- 22133875
TI  - Administration of BMP2/7 in utero partially reverses Rubinstein-Taybi syndrome
      like skeletal defects induced by Pdk1 or Cbp mutations in mice.
AB  - Mutations in the coactivator CREB-binding protein (CBP) are a major cause of the
      human skeletal dysplasia Rubinstein-Taybi syndrome (RTS); however, the mechanism
      by which these mutations affect skeletal mineralization and patterning is
      unknown. Here, we report the identification of 3-phosphoinositide-dependent
      kinase 1 (PDK1) as a key regulator of CBP activity and demonstrate that its
      functions map to both osteoprogenitor cells and mature osteoblasts. In
      osteoblasts, PDK1 activated the CREB/CBP complex, which in turn controlled runt
      related transcription factor 2 (RUNX2) activation and expression of bone
      morphogenetic protein 2 (BMP2). These pathways also operated in vivo, as
      evidenced by recapitulation of RTS spectrum phenotypes with osteoblast-specific
      Pdk1 deletion in mice (Pdk1osx mice) and by the genetic interactions observed in
      mice heterozygous for both osteoblast-specific Pdk1 deletion and either Runx2 or
      Creb deletion. Finally, treatment of Pdk1osx and Cbp+/- embryos with BMPs in
      utero partially reversed their skeletal anomalies at birth. These findings
      illustrate the in vivo function of the PDK1-AKT-CREB/CBP pathway in bone
      formation and provide proof of principle for in utero growth factor
      supplementation as a potential therapy for skeletal dysplasias.

PMID- 22133877
TI  - Intravital imaging of CTLs killing islet cells in diabetic mice.
AB  - Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin
      producing beta cells in the pancreatic islets, which are essentially mini-organs
      embedded in exocrine tissue. CTLs are considered to have a predominant role in
      the autoimmune destruction underlying T1D. Visualization of CTL-mediated killing
      of beta cells would provide new insight into the pathogenesis of T1D, but has
      been technically challenging to achieve. Here, we report our use of intravital 2
      photon imaging in mice to visualize the dynamic behavior of a virally expanded,
      diabetogenic CTL population in the pancreas at cellular resolution. Following
      vascular arrest and extravasation, CTLs adopted a random motility pattern
      throughout the compact exocrine tissue and displayed unimpeded yet nonlinear
      migration between anatomically nearby islets. Upon antigen encounter within
      islets, a confined motility pattern was acquired that allowed the CTLs to scan
      the target cell surface. A minority of infiltrating CTLs subsequently arrested at
      the beta cell junction, while duration of stable CTL-target cell contact was on
      the order of hours. Slow-rate killing occurred in the sustained local presence of
      substantial numbers of effector cells. Collectively, these data portray the
      kinetics of CTL homing to and between antigenic target sites as a stochastic
      process at the sub-organ level and argue against a dominant influence of
      chemotactic gradients.

PMID- 22133876
TI  - Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR.
AB  - Oncogenic Ras and p53 loss-of-function mutations are common in many advanced
      sporadic malignancies and together predict a limited responsiveness to
      conventional chemotherapy. Notably, studies in cultured cells have indicated that
      each of these genetic alterations creates a selective sensitivity to ataxia
      telangiectasia and Rad3-related (ATR) pathway inhibition. Here, we describe a
      genetic system to conditionally reduce ATR expression to 10% of normal levels in
      adult mice to compare the impact of this suppression on normal tissues and
      cancers in vivo. Hypomorphic suppression of ATR minimally affected normal bone
      marrow and intestinal homeostasis, indicating that this level of ATR expression
      was sufficient for highly proliferative adult tissues. In contrast, hypomorphic
      ATR reduction potently inhibited the growth of both p53-deficient fibrosarcomas
      expressing H-rasG12V and acute myeloid leukemias (AMLs) driven by MLL-ENL and N
      rasG12D. Notably, DNA damage increased in a greater-than-additive fashion upon
      combining ATR suppression with oncogenic stress (H-rasG12V, K-rasG12D, or c-Myc
      overexpression), indicating that this cooperative genome-destabilizing
      interaction may contribute to tumor selectivity in vivo. This toxic interaction
      between ATR suppression and oncogenic stress occurred without regard to p53
      status. These studies define a level of ATR pathway inhibition in which the
      growth of malignancies harboring oncogenic mutations can be suppressed with
      minimal impact on normal tissue homeostasis, highlighting ATR inhibition as a
      promising therapeutic strategy.

PMID- 22133878
TI  - Decreased cardiac L-type Ca2+ channel activity induces hypertrophy and heart
      failure in mice.
AB  - Antagonists of L-type Ca2+ channels (LTCCs) have been used to treat human
      cardiovascular diseases for decades. However, these inhibitors can have untoward
      effects in patients with heart failure, and their overall therapeutic profile
      remains nebulous given differential effects in the vasculature when compared with
      those in cardiomyocytes. To investigate this issue, we examined mice heterozygous
      for the gene encoding the pore-forming subunit of LTCC (calcium channel, voltage
      dependent, L type, alpha1C subunit [Cacna1c mice; referred to herein as alpha1C
      /+ mice]) and mice in which this gene was loxP targeted to achieve graded heart
      specific gene deletion (termed herein alpha1C-loxP mice). Adult cardiomyocytes
      from the hearts of alpha1C-/+ mice at 10 weeks of age showed a decrease in LTCC
      current and a modest decrease in cardiac function, which we initially
      hypothesized would be cardioprotective. However, alpha1C-/+ mice subjected to
      pressure overload stimulation, isoproterenol infusion, and swimming showed
      greater cardiac hypertrophy, greater reductions in ventricular performance, and
      greater ventricular dilation than alpha1C+/+ controls. The same detrimental
      effects were observed in alpha1C-loxP animals with a cardiomyocyte-specific
      deletion of one allele. More severe reductions in alpha1C protein levels with
      combinatorial deleted alleles produced spontaneous cardiac hypertrophy before 3
      months of age, with early adulthood lethality. Mechanistically, our data suggest
      that a reduction in LTCC current leads to neuroendocrine stress, with sensitized
      and leaky sarcoplasmic reticulum Ca2+ release as a compensatory mechanism to
      preserve contractility. This state results in calcineurin/nuclear factor of
      activated T cells signaling that promotes hypertrophy and disease.

PMID- 22133879
TI  - Human dental pulp-derived stem cells promote locomotor recovery after complete
      transection of the rat spinal cord by multiple neuro-regenerative mechanisms.
AB  - Spinal cord injury (SCI) often leads to persistent functional deficits due to
      loss of neurons and glia and to limited axonal regeneration after injury. Here we
      report that transplantation of human dental pulp stem cells into the completely
      transected adult rat spinal cord resulted in marked recovery of hind limb
      locomotor functions. Transplantation of human bone marrow stromal cells or skin
      derived fibroblasts led to substantially less recovery of locomotor function. The
      human dental pulp stem cells exhibited three major neuroregenerative activities.
      First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and
      oligodendrocytes, which improved the preservation of neuronal filaments and
      myelin sheaths. Second, they promoted the regeneration of transected axons by
      directly inhibiting multiple axon growth inhibitors, including chondroitin
      sulfate proteoglycan and myelin-associated glycoprotein, via paracrine
      mechanisms. Last, they replaced lost cells by differentiating into mature
      oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that
      tooth-derived stem cells may provide therapeutic benefits for treating SCI
      through both cell-autonomous and paracrine neuroregenerative activities.

PMID- 22133880
TI  - Histamine-releasing factor has a proinflammatory role in mouse models of asthma
      and allergy.
AB  - IgE-mediated activation of mast cells and basophils underlies allergic diseases
      such as asthma. Histamine-releasing factor (HRF; also known as translationally
      controlled tumor protein [TCTP] and fortilin) has been implicated in late-phase
      allergic reactions (LPRs) and chronic allergic inflammation, but its functions
      during asthma are not well understood. Here, we identified a subset of IgE and
      IgG antibodies as HRF-interacting molecules in vitro. HRF was able to dimerize
      and bind to Igs via interactions of its N-terminal and internal regions with the
      Fab region of Igs. Therefore, HRF together with HRF-reactive IgE was able to
      activate mast cells in vitro. In mouse models of asthma and allergy, Ig
      interacting HRF peptides that were shown to block HRF/Ig interactions in vitro
      inhibited IgE/HRF-induced mast cell activation and in vivo cutaneous anaphylaxis
      and airway inflammation. Intranasally administered HRF recruited inflammatory
      immune cells to the lung in naive mice in a mast cell- and Fc receptor-dependent
      manner. These results indicate that HRF has a proinflammatory role in asthma and
      skin immediate hypersensitivity, leading us to suggest HRF as a potential
      therapeutic target.

PMID- 22133881
TI  - Pancreatic ductal cells in development, regeneration, and neoplasia.
AB  - The pancreas is a complex organ comprised of three critical cell lineages: islet
      (endocrine), acinar, and ductal. This review will focus upon recent insights and
      advances in the biology of pancreatic ductal cells. In particular, emphasis will
      be placed upon the regulation of ductal cells by specific transcriptional factors
      during development as well as the underpinnings of acinar-ductal metaplasia as an
      important adaptive response during injury and regeneration. We also address the
      potential contributions of ductal cells to neoplastic transformation,
      specifically in pancreatic ductal adenocarcinoma.

PMID- 22133882
TI  - Preventing sexually transmitted infections: back to basics.
AB  - Sexually transmitted infections (STIs) have plagued humans for millennia and can
      result in chronic disease, pregnancy complications, infertility, and even death.
      Recent technological advances have led to a better understanding of the causative
      agents for these infections as well as aspects of their pathogenesis that might
      represent novel therapeutic targets. The articles in this Review Series provide
      excellent updates on the recent advances in understanding of the pathogenesis of
      some very important and persistent STIs and discuss the importance of considering
      each pathogen in the broader context of the environment of the individual who it
      infects.

PMID- 22133884
TI  - The known unknowns of HPV natural history.
AB  - The discovery that certain high-risk strains of human papillomavirus (HR-HPV)
      cause nearly 100% of invasive cervical cancer has spurred a revolution in
      cervical cancer prevention by promoting the development of viral vaccines.
      Although the efficacy of these vaccines has already been demonstrated, a complete
      understanding of viral latency and natural immunity is lacking, and solving these
      mysteries could help guide policies of cervical cancer screening and vaccine use.
      Here, we examine the epidemiological and biological understanding of the natural
      history of HPV infection, with an eye toward using these studies to guide the
      implementation of cervical cancer prevention strategies.

PMID- 22133883
TI  - Syphilis: using modern approaches to understand an old disease.
AB  - Syphilis is a fascinating and perplexing infection, with protean clinical
      manifestations and both diagnostic and management ambiguities. Treponema pallidum
      subsp. pallidum, the agent of syphilis, is challenging to study in part because
      it cannot be cultured or genetically manipulated. Here, we review recent progress
      in the application of modern molecular techniques to understanding the biological
      basis of this multistage disease and to the development of new tools for
      diagnosis, for predicting efficacy of treatment with alternative antibiotics, and
      for studying the transmission of infection through population networks.

PMID- 22133886
TI  - Vaginal microbiome and sexually transmitted infections: an epidemiologic
      perspective.
AB  - Vaginal bacterial communities are thought to help prevent sexually transmitted
      infections. Bacterial vaginosis (BV) is a common clinical syndrome in which the
      protective lactic acid-producing bacteria (mainly species of the Lactobacillus
      genus) are supplanted by a diverse array of anaerobic bacteria.
      Epidemiologically, BV has been shown to be an independent risk factor for adverse
      outcomes including preterm birth, development of pelvic inflammatory disease, and
      acquisition of sexually transmitted infections. Longitudinal studies of the
      vaginal microbiome using molecular techniques such as 16S ribosomal DNA analysis
      may lead to interventions that shift the vaginal microbiota toward more
      protective states.

PMID- 22133887
TI  - Effect of verapamil on bronchial goblet cells of asthma: an experimental study on
      sensitized animals.
AB  - INTRODUCTION: Goblet cell hyperplasia (GCH) and mucus hypersecretion in the
      airway is recognized as an important contributor to morbidity and mortality in
      asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha
      subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin
      and CaM kinase pathway. The objective of this study was to determine the in vivo
      effect of verapamil on GCH and eosinophilic inflammation in sensitized mice.
      METHODS: Male BALB/c mice were sensitized to ovalbumin using the standard method.
      Two groups of animals were received verapamil via an intramuscular injection: 1
      low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two
      weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed
      for inflammatory cells, interferon-gamma and IL-4. The left lung was sent for
      histopathological evaluation, especially for periodic acid-Schiff (PAS), to
      identify goblet cells in the epithelium. The degree of inflammatory cell
      infiltration, including eosinophils, mucus plugging, and smooth muscle thickness
      of the airways were classified on a semi quantitative scale. RESULTS:
      Inflammatory cell infiltration in peribronchial and perivascular areas was
      observed in all sensitized groups. Eosinophils percentage in the BALF
      significantly decreased in verapamil-treated mice compared with sensitized mice
      (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio
      of airway goblet cells per epithelial cells were significantly lower in verapamil
      treated mice versus sensitized mice (1.57+/-1.30% for low dose; 1.50+/-0.93% for
      high dose versus 12.93+/-7.55%, P<0.05, respectively). Mucus production of goblet
      cells decreased significantly in verapamil-treated mice versus sensitized mice
      (mean score was 1.45+/-0.30 for low dose; 0.81+/-1.00 for high dose versus 2.85+/
      0.86 in the sensitized control group, P<0.05, respectively). The concentration of
      serum and BALF-IFN-gamma in verapamil-treated mice markedly increased by the
      verapamil treatment when compared to sensitized mice (15.1+/-0.43 versus 4.7+/
      0.96, P<0.05 and 91.8+/-47.7 versus 14.8+/-4.6, P<0.01, respectively).
      CONCLUSION: Verapamil is a useful drug with therapeutic targeting on GCH and a
      potential way to limit mucous production and improve bronchial inflammation.

PMID- 22133885
TI  - HSV-2: in pursuit of a vaccine.
AB  - Herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually
      transmitted infections worldwide. In addition to recurrent genital ulcers, HSV-2
      causes neonatal herpes, and it is associated with a 3-fold increased risk for HIV
      acquisition. Although many HSV-2 vaccines have been studied in animal models, few
      have reached clinical trials, and those that have been tested in humans were not
      consistently effective. Here, we review HSV-2 pathogenesis, with a focus on novel
      understanding of mucosal immunobiology of HSV-2, and vaccine efforts to date, in
      an attempt to stimulate thinking about future directions for development of
      effective prophylactic and therapeutic HSV-2 vaccines.

PMID- 22133888
TI  - VAP-1/SSAO plasma activity and brain expression in human hemorrhagic stroke.
AB  - BACKGROUND: Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating
      enzyme that belongs to the semicarbazide-sensitive amine oxidase (SSAO) family,
      which oxidatively deaminates primary amines and is implicated in leukocyte
      extravasation. Our aim was to investigate the alteration of soluble VAP-1/SSAO
      activity in plasma samples after acute intracerebral hemorrhage (ICH) and its
      presence in human ICH brain tissue. METHODS: VAP-1/SSAO activity was determined
      in plasma of 66 ICH patients and 58 healthy controls. In addition, we assessed
      the expression of VAP-1/SSAO in postmortem brain tissue from hemorrhagic stroke
      patients by Western blot and immunohistochemistry. RESULTS: We observed
      significantly higher levels of plasma VAP-1/SSAO activity in patients with ICH
      compared to matched elderly controls (p = 0.001). Plasma VAP-1/SSAO activity <2.7
      pmol/min.mg and baseline ICH volume <17 ml were independent predictors of
      neurological improvement after 48 h (OR 6.8, 95% CI 1.14-41.67, p = 0.035, and OR
      10.64, 95% CI 1.1-100, p = 0.041, respectively), after adjustment for baseline
      stroke severity. We also found that membrane-bound VAP-1/SSAO levels were lower
      in the perihematoma region than in the corresponding contralateral brain areas of
      patients deceased due to ICH (p = 0.024). CONCLUSIONS: Our data demonstrate that
      plasma VAP-1/SSAO activity is increased in ICH and predicts neurological outcome,
      suggesting a possible contribution of the soluble protein in secondary brain
      damage. Furthermore, anti-VAP-1/SSAO strategies might be a promising approach to
      prevent neurological worsening following ICH.

PMID- 22133889
TI  - [How to evaluate renal function in cancer patients].
AB  - The evaluation of renal function in patients with cancer is necessary. Measuring
      the actual glomerular filtration rate of the patient is the gold standard. This
      is usually done using a measure of the renal clearance of a marker of glomerular
      filtration rate (inulin) or a radio-marker (EDTA Chrome 51, (51)Cr-EDTA).
      However, these measures are complex and very constraining for the patient and in
      terms of organization and equipment. It is possible to estimate renal function by
      calculation. There are in the literature many evaluation formulae available.
      However, it is essential to use a tool reliable enough to determine an
      appropriate estimate of renal function, and adjust the doses of treatment if
      necessary. The choice of the abreviated MDRD (aMDRD) formula is so far the
      recommended option in oncology.

PMID- 22133890
TI  - Letter to the editor of "Evaluation on a decision protocol for type of delivery
      of infants in breech presentation at term" from S. Michel and colleagues.

PMID- 22133891
TI  - Gene pathway analysis of the mechanism by which the Rho-associated kinase
      inhibitor Y-27632 inhibits apoptosis in isolated thawed human embryonic stem
      cells.
AB  - Cryopreservation is an essential technique in basic research and clinical
      applications of human embryonic stem (hES) cells. Cryopreserved hES cells are
      fragile and undergo post-thaw apoptosis. We performed gene pathway analysis on
      cryopreserved and thawed hES cells to examine the effect of Y-27632, a Rho
      associated kinase (ROCK) inhibitor, on apoptosis and associated molecular events.
      Y-27632 was added to the cryopreservation solution and/or the post-thaw medium of
      two hES cell lines (KhES-1, KhES-3). Post-thaw apoptosis was recorded as a
      function of time using Giemsa staining and the terminal deoxynucleotidyl
      transferase dUTP nick end labeling assay. Apoptosis plateaued 12h after the
      untreated hES cells were thawed. Gene pathway analysis showed the activation of
      IL-1beta, TGF-beta, and their respective receptors (IL-1R, ACVR1C) in the mitogen
      activated protein kinase (MAPK) pathway, which resulted in the upregulation of
      caspase-8 and -10. Quantitative RT-PCR confirmed the upregulation of IL-1beta,
      TGF-beta, their respective receptors, and caspase-10 and -3. As these molecules
      were suppressed by Y-27632, gene pathways involving these molecules probably
      depend on ROCK activation. The TGF-beta receptor antagonist, SB-431542, and an
      inhibitor of p38MAPK, SB-203580, did not affect apoptosis. Combining Y-27632 with
      SB-203580, however, resulted in an increase in the survival rate compared with
      the control. This suggests that the initiation of apoptosis depends on cytokine
      interactions and multiple ways exist to reduce post-thaw apoptosis in hES cells.
      Y-27632 can suppress cytokine interactions and the MAPK pathway, thereby reducing
      the occurrence of apoptosis, and is an effective cryoprotectant for hES cells.

PMID- 22133893
TI  - Changes in the serotonergic system and in brain-derived neurotrophic factor
      distribution in the main olfactory bulb of pcd mice before and after mitral cell
      loss.
AB  - The serotonergic centrifugal system innervating the main olfactory bulb (MOB)
      plays a key role in the modulation of olfactory processing. We have previously
      demonstrated that this system suffers adaptive changes under conditions of a lack
      of olfactory input. The present work examines the response of this centrifugal
      system after mitral cell loss in the Purkinje cell degeneration (pcd) mutant
      mice. The distribution and density of serotonergic centrifugal axons were studied
      in the MOB of control and pcd mice, both before and after the loss of mitral
      cells, using serotonin (5-HT) and 5-HT transporter immunohistochemistry. Studies
      of the amount of 5-HT and its metabolite, 5-hydroxyindole acetic acid (5-HIAA),
      were performed by means of high-performance liquid chromatography (HPLC), and the
      relative amounts of brain-derived neurotrophin factor, BDNF, and its major
      receptor, tropomyosin-related kinase B (TrkB), were measured by Western blot. Our
      study revealed that the serotonergic system develops adaptive changes after, but
      not before, mitral cell loss. The lack of the main bulbar projection cells causes
      a decrease in the serotonergic input received by the MOB, whereas the number of
      serotonergic cells in the raphe nuclei remains constant. In addition, one of the
      molecules directly involved in serotonergic sprouting, the neurotrophin BDNF and
      its main receptor TrkB, underwent alterations in the MOBs of the pcd animals even
      before the loss of mitral cells. These data indicate that serotonergic function
      in the MOB is closely related to olfactory activity and that mitral cell loss
      induces serotonergic plastic responses.

PMID- 22133892
TI  - Estradiol acts via estrogen receptors alpha and beta on pathways important for
      synaptic plasticity in the mouse hippocampal formation.
AB  - Estradiol affects hippocampal-dependent spatial memory and underlying structural
      and electrical synaptic plasticity in female mice and rats. Using estrogen
      receptor (ER) alpha and beta knockout mice and wild-type littermates, we
      investigated the role of ERs in estradiol effects on multiple pathways important
      for hippocampal plasticity and learning. Six hours of estradiol administration
      increased immunoreactivity for phosphorylated Akt throughout the hippocampal
      formation, whereas 48 h of estradiol increased immunoreactivity for
      phosphorylated TrkB receptor. Estradiol effects on phosphorylated Akt and TrkB
      immunoreactivities were abolished in ER alpha and ER beta knockout mice.
      Estradiol also had distinct effects on immunoreactivity for post-synaptic density
      95 (PSD-95) and brain derived-neurotrophic factor (BDNF) mRNA in ER alpha and
      beta knockout mice. Thus, estradiol acts through both ERs alpha and beta in
      several subregions of the hippocampal formation. The different effects of
      estradiol at 6 and 48 h indicate that several mechanisms of estrogen receptor
      signaling contribute to this female hormone's influence on hippocampal synaptic
      plasticity. By further delineating these mechanisms, we will better understand
      and predict the effects of endogenous and exogenous ovarian steroids on mood,
      cognition, and other hippocampal-dependent behaviors.

PMID- 22133895
TI  - Distribution of lymph node metastases is an independent predictor of survival for
      sigmoid colon and rectal cancer.
AB  - OBJECTIVE: This study evaluated the prognostic significance of the distribution
      of lymph node metastases (LND) in patients with colorectal cancer. BACKGROUND:
      The impact of the LND on survival in colorectal cancer is unknown. METHODS: A
      total of 1205 consecutive patients who underwent potentially curative surgery for
      sigmoid colon or rectal cancer with high ligation of the inferior mesenteric
      artery (IMA) from January 1997 to February 2008 were assigned to 4 groups based
      on LND: LND0, no lymph node metastases-615 patients (51.0%); LND1, metastases in
      the pericolic nodes-324 patients (26.9%); LND2, metastases in the intermediate
      nodes-172 patients (14.3%); and LND3, node metastases at the origin of the IMA-94
      patients (7.8%). RESULTS: The 5-year overall survival rates of patients with
      LND0, LND1, LND2, and LND3 were 83%, 63%, 52%, and 28%, respectively (P < 0.001).
      The 5-year disease-free survival rates of patients with LND0, LND1, LND2, and
      LND3 were 83%, 54%, 43%, and 21%, respectively (P < 0.001). On multivariate
      analysis, LND was an independent prognostic factor for both overall survival and
      disease-free survival. However, the 5-year local recurrence-free survival rate
      was not inversely related to the LND. On a subset analysis that compared stage
      III disease with stage IV disease, the 5-year overall survival and disease-free
      survival rates were 45% and 31% for the patients with stage IV disease compared
      with 40% and 32% for the patients with stage III, LND3 disease, respectively (P =
      0.761 and 0.704). For the patients with pN1 tumors, the overall survival and
      disease-free survival did not differ significantly according to the LND (P =
      0.471 and 0.347, respectively). However, for patients with pN2 tumors, the
      overall survival and disease-free survival curves among the LND groups
      significantly differed (P < 0.001 and <0.001, respectively). CONCLUSION: LND is
      an independent predictor of survival for colorectal cancer patients, but it does
      not predict local recurrence. The N categorization including LND may enhance the
      prognostic value of the TNM staging system for patients with node-positive
      sigmoid colon or rectal cancer.

PMID- 22133894
TI  - Critical role of activated protein C in early coagulopathy and later organ
      failure, infection and death in trauma patients.
AB  - BACKGROUND: Recent studies have identified an acute traumatic coagulopathy that
      is present on admission to the hospital and is independent of iatrogenic causes.
      We have previously reported that this coagulopathy is due to the association of
      severe injury and shock and is characterized by a decrease in plasma protein C
      (PC) levels. Whether this early coagulopathy and later propensity to infection,
      multiple organ failure and mortality are associated with the activation of PC
      pathway has not been demonstrated and constitutes the aim of this study. METHODS
      AND FINDINGS: This was a prospective cohort study of 203 major trauma patients.
      Serial blood samples were drawn on arrival in the emergency department, and at 6,
      12, and 24 hours after admission to the hospital. PT, PTT, Va, VIIIa, PC aPC t
      PA, and D-dimer levels were assayed. Comprehensive injury, resuscitation, and
      outcome data were prospectively collected. A total of 203 patients were enrolled.
      Patients with tissue hypoperfusion and severe traumatic injury showed a strong
      activation of the PC which was associated with a coagulopathy characterized by
      inactivation of the coagulation factors V and VIII and a derepression of the
      fibrinolysis with high plasma levels of plasminogen activator and high D-dimers.
      Elevated plasma levels of activated PC were significantly associated with
      increased mortality, organ injury, increased blood transfusion requirements, and
      reduced ICU ventilator-free days. Finally early depletion of PC after trauma is
      associated with a propensity to posttraumatic ventilator-associated pneumonia.
      CONCLUSIONS: Acute traumatic coagulopathy occurs in the presence of tissue
      hypoperfusion and severe traumatic injury and is mediated by activation of the PC
      pathway. Higher plasma levels of aPC upon admission are predictive of poor
      clinical outcomes after major trauma. After activation, patients who fail to
      recover physiologic plasma values of PC have an increased propensity to later
      nosocomial lung infection.

PMID- 22133897
TI  - Updates in venous disease.

PMID- 22133896
TI  - Trend of healthcare-associated infections in children: annual prevalence surveys
      in a research hospital in Italy, 2007-2010.
AB  - BACKGROUND: Annual prevalence surveys of healthcare-associated infections (HAIs)
      between 2007 and 2010 were conducted in the largest tertiary care children's
      hospital in Italy. During this period, actions to improve HAI prevention were
      implemented, including strengthened isolation measures; adoption of care bundles
      for invasive procedures; hand hygiene promotion using the World Health
      Organization multimodal strategy; and promotion of appropriate antimicrobial use.
      AIM: To determine the impact of these measures on HAI rates. METHODS: A total of
      1506 patients were surveyed. Information on patient demographics, mechanical
      ventilation, central line and urinary catheterization in the preceding 48 h, and
      surgery in the previous 30 days were abstracted from medical charts. The type and
      date of onset of HAIs, and microbiological data were recorded. Univariate and
      multivariate logistic analysis were used to evaluate changes in HAI rates over
      time, and the influence of ward type and patient characteristics. FINDINGS: There
      were significant (P < 0.001) reductions in the prevalence of patients developing
      HAI (from 7.6% to 4.3%) and in the prevalence of total HAIs (from 8.6 to 4.3 per
      100 patients). Factors independently associated with increased HAI risk were
      hospitalization in intensive care ward, length of stay >30 days, presence of
      invasive device, and age 6-11 years. CONCLUSION: This HAI prevention strategy was
      influential in decreasing infections among hospitalized children. Repeated
      prevalence surveys are an effective tool for monitoring HAI frequency, increasing
      awareness among the healthcare personnel, and contributing to the establishment
      of effective infection control.

PMID- 22133898
TI  - Invited commentary.

PMID- 22133899
TI  - Sinonasal persistence of Pseudomonas aeruginosa after lung transplantation.
AB  - We report on two CF patients who received double lung transplantation (LTX) due
      to Pseudomonas aeruginosa related pulmonary destruction. Prior to LTX we detected
      P. aeruginosa in nasal lavages (NL) and sputum cultures from both patients. Donor
      lungs of patient 1 became colonized within four weeks with P. aeruginosa
      identical in genotype with isolates from his pre-transplant sputum cultures and
      pre- and post-transplant NL. In contrast, patient 2 remained P. aeruginosa free
      in lower airway samples (bronchial lavage/sputum) for now up to 30 months,
      despite persistent detection of P. aeruginosa that was identical in genotype with
      pre-transplant NL and sputum isolates in NL and even in throat swabs. For
      prevention of pulmonary re-colonization patient 2 has continuously inhaled
      Colomycin 1 MIU once daily during the preceding more than 36 months with the
      novel Pari SinusTM nebulizer, which in scintigraphic studies was shown to deliver
      vibrating aerosols into paranasal sinuses, additional to bronchial antibiotic
      inhalation. DISCUSSION: Pulmonary colonization of transplanted donor lungs with
      identical clones previously colonizing the explanted lungs has been described
      previously and the upper airways were postulated as reservoir for descending
      colonization. However, this remained speculative, as upper airway sampling which
      does not belong to current standards, was not performed in these studies. Our
      report demonstrates persistence of identical P. aeruginosa genotypes in CF upper
      airways prior to and after LTX underlining risks of descending colonization of
      transplanted lungs with P. aeruginosa, which increases risks of graft
      dysfunction. Therefore, we recommend regular assessment of sinonasal colonization
      prior to and after LTX. Sinonasal inhalation with antimicrobials should be
      investigated in prospective trials.

PMID- 22133900
TI  - Combined proximal endografting with distal bare-metal stenting for management of
      aortic dissection.
AB  - BACKGROUND: Established endovascular treatments for aortic dissection often
      result in incomplete aortic repair, potentially leading to late complications
      involving the distal aorta. To address the problems of incomplete true lumen
      reconstitution and late aneurysmal change, we report the midterm results of
      combined proximal endografting with distal true lumen bare-metal stenting
      (STABLE: Staged Total Aortic and Branch vesseL Endovascular reconstruction) in
      Stanford type A and B aortic dissection. METHODS: Between January 2003 and
      January 2010, 31 patients underwent staged total aortic and branch vessel
      endovascular reconstruction for management of acute (type A, 13; type B, 11) and
      chronic (type B, 7) aortic dissection. Proximal endografting was combined with
      bare-metal Z stent implantation in the distal true lumen. Patients with type A
      dissection underwent adjunctive treatment at operation. Computed tomography
      angiography was performed at baseline, 1 year, and annually thereafter to assess
      aortic remodelling. RESULTS: Primary technical success was 97%. Thirty-day rates
      of death, stroke, and permanent paraplegia/paresis were 3% (n=1), 0%, and 0%,
      respectively. Mean follow-up was 57.3 months (range, 5 to 100 months). Overall
      survival was 60% at 100 months. Aortic-specific survival was 93%. Four patients
      (13%) underwent device-related reintervention. One (3%) late aortic-related death
      occurred. Thoracic (p=0.64) and abdominal (p=0.14) aortic dimensions were stable.
      The true lumen index increased significantly at follow-up. CONCLUSIONS: Staged
      total aortic and branch vessel endovascular reconstruction is a feasible
      ancillary endovascular technique to address the problems of distal true lumen
      collapse, incomplete aortic remodelling, and late aneurysm formation in aortic
      dissection.

PMID- 22133901
TI  - NMR-based conformational analysis of sphingomyelin in bicelles.
AB  - Sphingomyelin (SM) is a common sphingolipid in mammalian membranes and is known
      to be substantially involved in cellular events such as the formation of lipid
      rafts. Despite its biological significance, conformation of SM in a membrane
      environment remains unclear because the noncrystalline property and anisotropic
      environment of lipid bilayers hampers the application of X-ray crystallography
      and NMR measurements. In this study, to elucidate the conformation of SM in
      membranes, we utilized bicelles as a substitute for a lipid bilayer membrane.
      First, we demonstrated through (31)P NMR, (2)H NMR, and dynamic light scattering
      experiments that SM forms both oriented and isotropic bicelles by changing the
      ratio of SM/dihexanoyl phosphatidylcholine. Then, we determined the conformation
      of SM in isotropic bicelles on the basis of coupling constants and NOE
      correlations in (1)H NMR and found that the C2-C6 and amide groups of SM take a
      relatively rigid conformation in bicelles.

PMID- 22133903
TI  - VE-Cadherin(low)alpha-smooth muscle actin+ component of vascular progenitor cells
      correlates with the coronary artery Gensini score.
AB  - BACKGROUND: Vascular progenitor cells (VPCs) are a heterogeneous population,
      containing a subpopulation co-expressing both endothelial and smooth muscle
      phenotypes. This study sought to determine whether the level of this
      subpopulation correlated with the coronary Gensini score. METHODS AND RESULTS:
      VPCs were cultivated in 50 patients undergoing coronary angiography. A
      subpopulation of VPCs expressed both endothelial (VE-cadherin [VE-Cad]) and
      smooth-muscle phenotypes (alpha-smooth muscle actin [alpha-SMA]). Correlations of
      the VE-Cad(low)alpha-SMA(+) VPC level and adhesion molecule expression by VPCs
      with the Gensini score were investigated. The association between the amount of
      this subpopulation and the development of intimal hyperplasia (IH) was also
      estimated in a vascular injury animal model. Both the number of VE-Cad(low)alpha
      SMA(+) VPCs (P = 0.002) and the expression level of intracellular adhesion
      molecule (ICAM)-1 by VPCs (P = 0.008) correlated with the Gensini score. However,
      only the number of VE-Cad(low)alpha-SMA(+) VPCs (P = 0.004) and the blood level
      of low-density lipoprotein cholesterol (P = 0.016) were parameters independently
      associated with the Gensini score in multivariate analysis. Furthermore, in an
      animal model of injecting VPCs into SCID mice after femoral artery wire injury, a
      higher number of VE-Cad(low)alpha-SMA(+) VPCs correlated with greater IH (r =
      0.69, P<0.0001). CONCLUSIONS: The level of VE-Cad(low)alpha-SMA(+) VPCs was
      associated with the severity of coronary atherosclerosis as quantified by the
      Gensini score. Manipulating this subpopulation may provide a way of attenuating
      atherosclerosis in the future.

PMID- 22133902
TI  - Bicyclic benzofuran and indole-based salicylic acids as protein tyrosine
      phosphatase inhibitors.
AB  - Protein tyrosine phosphatases (PTPs) constitute a large and structurally diverse
      family of signaling enzymes that control the cellular levels of protein tyrosine
      phosphorylation. Malfunction of PTP activity has significant implications in many
      human diseases, and the PTP protein family provides an exciting array of
      validated diabetes/obesity (PTP1B), oncology (SHP2), autoimmunity (Lyp), and
      infectious disease (mPTPB) targets. However, despite the fact that PTPs have been
      garnering attention as novel therapeutic targets, they remain largely an untapped
      resource. The main challenges facing drug developers by the PTPs are inhibitor
      specificity and bioavailability. Work over the last ten years has demonstrated
      that it is feasible to develop potent and selective inhibitors for individual
      members of the PTP family by tethering together small ligands that can
      simultaneously occupy both the active site and unique nearby peripheral binding
      sites. Recent results with the bicyclic salicylic acid pharmacophores indicate
      that the new chemistry platform may provide a potential solution to overcome the
      bioavailability issue that has plagued the PTP drug discovery field for many
      years. Structural analysis of PTP-inhibitor complexes reveals molecular
      determinants important for the development of more potent and selective PTP
      inhibitors, thus offering hope in the medicinal chemistry of a largely
      unexploited protein class with a wealth of attractive drug targets.

PMID- 22133904
TI  - Differences in negative T waves between takotsubo cardiomyopathy and reperfused
      anterior acute myocardial infarction.
AB  - BACKGROUND: In both takotsubo cardiomyopathy (TC) and reperfused anterior acute
      myocardial infarction (AMI), negative T waves commonly appear on the ECG in the
      subacute phase. This study aimed to clarify the ECG differences between these
      diseases. METHODS AND RESULTS: We compared the ECGs with the greatest amplitude
      of negative T wave from 34 patients with TC and 237 patients with a first
      reperfused anterior AMI who were admitted within 6 h of symptom onset and who had
      no abnormal Q-waves on discharge ECG. Time from symptom onset to recording the
      ECG did not differ between TC and anterior AMI (2.4 +/- 1.5 vs. 2.1 +/- 2.0 days,
      P = 0.48). TC was associated with a greater maximal amplitude of negative T wave
      (1.00 +/- 0.44 vs. 0.79 +/- 0.46 mV, P = 0.044), and a greater number of leads
      with negative T waves (9.5 +/- 1.0 vs. 6.0 +/- 2.1, P<0.001). Negative T waves
      were consistently observed in leads -aV(R) and V(4-6), whereas negative T waves
      were rare in lead V(1) in TC. Negative T waves in lead -aV(R) (ie, positive T
      waves in lead aV(R)) and no negative T waves in lead V(1) identified TC with 94%
      sensitivity and 95% specificity, representing the highest diagnostic accuracy.
      CONCLUSIONS: During the subacute phase, deeper negative T waves were more
      frequently and broadly distributed, particularly around leads facing the apical
      region, in TC than in reperfused anterior AMI.

PMID- 22133905
TI  - Skeletal muscle is protected from disuse in hibernating dauria ground squirrels.
AB  - The purpose of this study is to test the hypothesis that muscle fibers are
      protected from undue atrophy in hibernating dauria ground squirrels (Spermophilus
      dauricus, Brandt). Muscle mass, fiber cross sectional area (CSA, video analysis)
      and fiber type distribution (m-ATPase staining) were determined in extensor
      digitorum longus (EDL) muscle from non-hibernating control animals (Pre-H), from
      animals who hibernated for one (H1) or two (H2) months, and from animals 2-4days
      after arousal (Post-H; N=8 each). Muscle wet weight decreased less than body
      weight in hibernating animals, resulting in a steady increase in muscle-to-body
      mass ratio (+37% in Post-H compared to Pre-H, p<0.001). In the Pre-H group, Type
      I (6.3+/-2.0%) and II (93.7+/-2.0%) fiber CSAs were 1719+/-201 and 2261+/
      287MUm(2), respectively. There was a tendency (n.s.) of larger CSA of type I in
      hibernators compared to pre-H. In the Post-H group, fiber CSA and type
      distribution were not different from Pre-H. We are the first to report data on
      EDL fiber type distribution and confirm a protective effect that prevents muscle
      atrophy in spite of prolonged disuse during hibernation in dauria ground
      squirrels.

PMID- 22133906
TI  - Symptom severity and attitudes toward medication: impacts on adherence in
      outpatients with schizophrenia.
AB  - OBJECTIVE: The primary aim of this study was to compare electronic monitoring
      with other measures of adherence to antipsychotic medication in outpatients with
      schizophrenia. The secondary aim of the study was to analyze the relationships
      between adherence and other clinical parameters. METHOD: Fifty-one patients
      diagnosed with schizophrenia were monitored over an eight-week period. Medication
      adherence was assessed using the Medication Event Monitoring System (MEMS), which
      is a bottle cap with a microprocessor that records the occurrence and times of
      bottle opening, patient self-reports, a clinician rating scale, and pill counts.
      Agreements among adherence measures and the relationships between adherence and
      other clinical factors were assessed. RESULTS: The rate of non-adherence
      according to the MEMS was 41.2%, considerably higher than those of pill counting
      (7.8%), clinician rating scale (7.8%), or self-reporting (25.5%). Excitement,
      impulse control, and preoccupation symptoms on the Positive and Negative Syndrome
      Scale (PANSS) were higher in the non-adherent patients than in the adherent
      patients. The full Drug Attitude Inventory (DAI) score was higher in adherent
      versus non-adherent patients and the significant other subscale of the
      Multidimensional Scale of Perceived Social Support score was lower in the
      adherent patients. The Clinical Global Impression-Severity score was negatively
      correlated with adherence as measured by the MEMS (r=-0.426, p<0.05) and DAI
      scores were positively correlated with adherence according to the MEMS and the
      clinician rating scale (r=0.498, p<0.01 and r=0.387, p<0.05). Multivariate
      analysis showed that PANSS and DAI scores significantly contributed to MEMS
      adherence. CONCLUSION: Adherence as measured by the MEMS showed a discrepancy
      with other measures of adherence in patients with schizophrenia. The severity of
      disease and attitudes toward medication were related to adherence. Further
      studies are needed to evaluate the impacts of medication adherence in
      schizophrenia.

PMID- 22133907
TI  - Intracranial atherosclerosis is associated with progression of neurological
      deficit in subcortical stroke.
AB  - BACKGROUND: Progression of neurological deficit (PND) is a frequent complication
      of acute subcortical ischemic stroke (SCS). The role of intracranial
      atherosclerosis (IAS) in PND is controversial. Our goal was to evaluate IAS on
      admission, as predictor of PND in SCS patients. METHODS: SCS patients were
      identified from our prospective database from 2004 to 2008. Clinical and
      laboratory data were collected from charts, and radiographic data from original
      radiographs. The proximal intracranial arteries were graded as patent, irregular,
      stenotic, or occlusion. IAS was defined as irregularity or stenosis. PND was
      defined as a change in the National Institutes of Health Stroke Scale >1 point.
      RESULTS: Two hundred and two SCS patients were identified. In 14%, PND occurred
      at a median of 2 days from onset. Univariate analysis by infarct location showed
      the following to be associated with PND: for anterior circulation infarcts
      (centrum semiovale/basal ganglia), M1 atherosclerosis (p = 0.042); for posterior
      circulation infarcts, vertebral artery atherosclerosis (p = 0.018). For both
      groups, we found a non-significant association with age (p = 0.2) and HbA1c
      levels (p = 0.095). No association was found with admission glucose levels.
      Multivariate analysis showed the following association with PND: for anterior
      circulation infarcts, M1 atherosclerosis (OR 4.7; 95% CI 1.2-18.8; p = 0.03); for
      pontine infarcts, vertebral artery atherosclerosis (OR 5.8; 95% CI 1.1-29.4; p =
      0.033). There was an increase in PND likelihood with an increasing number of
      atherosclerotic vessels. DISCUSSION: In our cohort of SCS patients, PND was
      associated with IAS of the responsible vessels. These results suggest a role for
      IAS in the pathogenesis of PNF in SCS patients.

PMID- 22133908
TI  - Meta-analysis of GnRH antagonist protocols: do they reduce the risk of OHSS in
      PCOS?
AB  - This systematic review and meta-analysis investigated whether gonadotrophin
      releasing hormone (GnRH) antagonist protocols reduce the risk of ovarian
      hyperstimulation syndrome (OHSS) in women with polycystic ovary syndrome
      undergoing IVF compared with the long agonist protocol. Searches were conducted
      on MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI
      Conference Proceedings. Primary outcome was OHSS incidence. Secondary outcomes
      were total duration and dose of gonadotrophin, number of oocytes retrieved and
      clinical pregnancy and miscarriage rates. A total of 966 women were included in
      nine randomized controlled trials. There was inconsistency in definition,
      classification of severity and reporting of the OHSS rate. There was no
      difference in the incidence of severe OHSS in the antagonist group compared with
      the long agonist group (relative risk 0.61; 95% CI 0.23 to 1.64). However, when
      all moderate and severe OHSS cases were pooled, the antagonist protocol was
      associated with significantly lower risk of OHSS (relative risk 0.60; 95% CI 0.48
      0.76; P<0.0001). A possible reduction in the incidence of severe OHSS with the
      GnRH antagonist protocol should be viewed with caution since the data is
      inconclusive. Larger randomized trials with adequate sample size and standardized
      definition, classification and diagnosis of OHSS remain necessary.

PMID- 22133909
TI  - Computerized cell-scanning system for evaluating human spermatogenesis in non
      obstructive azoospermic patients.
AB  - There may be incompatibility between testicular histopathological evaluation and
      testicular sperm extraction (TESE) outcome. Assessment for sperm presence and
      different pathological disturbances of non-obstructive azoospermia (NOA) remains
      challenging. An assay for maximal sampling and accurate identification of
      testicular cells from NOA patients undergoing TESE and autopsied fertile controls
      was developed. Testicular cells stained and scanned automatically for morphology
      underwent fluorescence in-situ hybridization using centromeric probes for
      chromosomes X, Y and 18 after destaining. Cells were automatically classified
      according to ploidy, and ratios of haploid cells and autosomal (18) and sex
      chromosome bivalent rates were calculated. Identification of testicular cells in
      suspension enabled prediction of spermatogenesis in seven of eight Sertoli-cell
      only syndrome patients. Haploid/diploid cell ratios were 67.6:32.2 for controls
      and 9.6:90.4 for patients. Both autosomal (18) and sex-chromosome bivalents were
      present in patients (4.1 +/- 5.82%) and controls (19.7 +/- 8.95%). Few tetraploid
      pachytene spermatocytes were observed. More secondary spermatocytes with NOA
      showed two distinct signals for chromosome 18 (27.9 +/- 32.69%) compared with
      controls (0.4 +/- 0.35%). The computerized cell-scanning system enables
      simultaneous application of morphology and chromosome analysis of testicular
      cells, which enhance assessing different pathological disturbances and estimating
      the likelihood of a successful second TESE procedure.

PMID- 22133910
TI  - Concentrations of organochlorine pesticides and 2,4,6-trichloroanisole in cork
      bark.
AB  - Organochlorine pesticides are persistent lipophilic organic pollutants and tend
      to accumulate in growing plants. During growth, cork is in contact with the open
      air for long periods (9-12 years). Owing to the previous widespread use of
      organochlorine pesticides and their high persistence in the environment, there is
      a risk that residues of such pesticides may be present in cork. In this study,
      the concentrations of 14 organochlorine pesticides-all of which are indicators of
      environmental pollution-were analyzed in cork bark samples from three regions in
      Spain and one in Portugal. In addition, the concentrations of 2,4,6
      trichlorophenol (TCP) and 2,4,6-trichloroanisole (TCA) were also analyzed. Our
      results show only very low concentrations of lindane, gamma-HCH (<2.6 ng g(-1))
      and its byproducts alpha-HCH (<3.5 ng g(-1)) and beta-HCH (<0.6 ng g(-1)). Among
      the DDT and its metabolites, only two were found: p,p'-DDT was found in a cork
      sample from Extremadura (0.1 ng g(-1)) and p,p'-DDE was present at a maximum
      concentration of 2.9 ng g(-1) in a cork sample from Castile-La Mancha. However,
      all concentrations were well below the legal limit established by Regulation (EC)
      No. 396/2005 (10 ng g(-1) in foodstuffs). We can conclude, therefore, that the
      cork samples we studied complied with food safety standards.

PMID- 22133911
TI  - Effect of fungicides on plant growth promoting activities of phosphate
      solubilizing Pseudomonasputida isolated from mustard (Brassica compestris)
      rhizosphere.
AB  - This study was navigated to examine the effects of fungicide-stress on the
      activities of plant-growth-promoting rhizobacterium Pseudomonasputida with
      inherent phosphate solubilizing activity. The fungicide-tolerant and phosphate
      solubilizing P.putida strain PS9 was isolated from the mustard rhizosphere and
      tentatively identified following standard morphological, physiological and
      biochemical tests. To further consolidate the identity of the strain PS9, the 16S
      rDNA sequence analysis was performed. Following the BLAST program, the strain PS9
      was identified as P.putida. In the presence of the varying concentrations (0-3200
      MUg mL(-1); at a two fold dilution interval) of four fungicides of different
      chemical families (tebuconazole, hexaconazole, metalaxyl and kitazin) amended in
      minimal salt agar medium, the P.putida strain PS9 showed a variable tolerance
      levels (1400-3200 MUg mL(-1)) against the tested fungicides. The strain PS9
      produced plant-growth-promoting (PGP) substances in significant amount in the
      absence of fungicides. In general, fungicides applied at the recommended, two and
      three times of the recommended rates, decreased the PGP attributes of P.putida
      the strain PS9 and affected the PGP activities in concentration-dependent manner.
      Fungicides at the recommended dose had minor reducing effect while the doses
      higher than the recommended dose significantly reduced the PGP activities
      (phosphate solubilization, salicylic acid, 2,3-dihydroxy benzoic acid, and indole
      3-acetic acid production except exo-polysaccharides, hydrogen cyanate and ammonia
      production). Of the four fungicides, tebuconazole generally, showed maximum
      toxicity to the PGP activities of the strain PS9. This study inferred that
      fungicides must be examined in vitro for their possible adverse effects on soil
      micro flora before their application in agricultural fields. Moreover, the
      results also suggested the prerequisite of application of fungicide-tolerant PGPR
      strains as bioinoculants so that their PGP activities may not be suppressed under
      fungicide stress.

PMID- 22133912
TI  - PCR-ELISA detection of estrogen receptor beta mRNA expression and plasma
      vitellogenin induction in juvenile sole (Solea solea) exposed to waterborne 4
      nonylphenol.
AB  - In this study, the effect of 4-nonylphenol (4NP) on reproductive axis of sole
      (Solea solea) has been investigated by using selected biomarkers of estrogenic
      effects: vitellogenin (VTG) and estrogen receptor beta (ERbeta) mRNA.
      Furthermore, an enzyme linked immunosorbent assay (ELISA) detection system of
      reverse transcriptase-polymerase chain reaction (RT-PCR) products for the
      analysis of sole ERbeta mRNA expression was developed and validated. The proposed
      method allows large-scale analyses of different mRNAs in fast and not expensive
      way. Our results have demonstrated that the PCR-ELISA method developed shows high
      sensitivity, good reproducibility and also the potential for semi-quantitative
      analysis of hepatic ERbeta mRNAs. Both plasma VTG level and ERbeta mRNA
      expression were increased in tested animals following a short exposure to
      environmental relevant concentrations (10(-6)M) of 4NP, confirming the functional
      role of ERbeta in the regulation of xenoestrogens-induced production of VTG. The
      methodology provided in the present study together with the preliminary results
      on the hepatic expression of ERbeta may be useful in environmental xenoestrogens
      monitoring studies, using flatfish as "sentinel" species.

PMID- 22133913
TI  - Intra-particle migration of mercury in granular polysulfide-rubber-coated
      activated carbon (PSR-AC).
AB  - The depth profile of mercuric ion after the reaction with polysulfide-rubber
      coated activated carbon (PSR-AC) was investigated using micro-X-ray fluorescence
      (MU-XRF) imaging techniques and mathematical modeling. The MU-XRF results
      revealed that mercury was concentrated at 0-100 MUm from the exterior of the
      particle after 3 months of treatment with PSR-AC in 10 ppm HgCl(2) aqueous
      solution. The MU-X-ray absorption near edge spectroscopic (MU-XANES) analyses
      indicated HgS as a major mercury species, and suggested that the intra-particle
      mercury transport involved a chemical reaction with PSR polymer. An intra
      particle mass transfer model was developed based on either a Langmuir sorption
      isotherm with liquid phase diffusion (Langmuir model) or a kinetic sorption with
      surface diffusion (kinetic sorption model). The Langmuir model predicted the
      general trend of mercury diffusion, although at a slower rate than observed from
      the MU-XRF map. A kinetic sorption model suggested faster mercury transport,
      which overestimated the movement of mercuric ions through an exchange reaction
      between the fast and slow reaction sites. Both MU-XRF and mathematical modeling
      results suggest mercury removal occurs not only at the outer surface of the PSR
      AC particle but also at some interior regions due to a large PSR surface area
      within an AC particle.

PMID- 22133915
TI  - [Chemotherapy of metastatic pancreatic adenocarcinoma: challenges and encouraging
      results].
AB  - The outcome for patients with metastatic pancreatic ductal adenocarcinoma is
      dismal. In this article, we will review current first-line treatments for
      metastatic pancreatic adenocarcinoma focusing on phase III randomized studies.
      Single-agent gemcitabine, the reference treatment since 1995, offers only slight
      benefit. Numerous trials using gemcitabine in combination with different
      cytotoxic agents have resulted in no major improvement compared to gemcitabine
      alone. Only the gemcitabine-erlotinib combination has shown a small, but
      statistically improvement in survival. In selected patients with good performance
      status ECOG 0-1, no cardiac ischemia and almost normal bilirubin level, the
      Folfirinox regimen, when compared to gemcitabine as single agent, was associated
      with more toxicities, but also with significant increased survival and delay in
      the degradation of quality of life. So, Folfirinox is a new more toxic and more
      efficient regimen that may be considered in patients with good performance
      status.

PMID- 22133914
TI  - Effect of Alzheimer caregiving on circulating levels of C-reactive protein and
      other biomarkers relevant to cardiovascular disease risk: a longitudinal study.
AB  - BACKGROUND: Providing care to a spouse with Alzheimer's disease (AD) may
      contribute to cardiovascular disease (CVD). The acute phase reactant C-reactive
      protein (CRP) is a well-established biomarker of an increased CVD risk.
      OBJECTIVE: To investigate the hypothesis that dementia caregiving is associated
      with elevated circulating levels of CRP and possibly other biomarkers of CVD
      risk. METHODS: We examined 118 elderly spousal Alzheimer caregivers and 51
      noncaregiving controls about once a year for up to 3 years. Random regression
      models with fixed and time-variant effects for a range of covariates known to
      affect biomarker levels were used to evaluate changes in CRP and in 12 additional
      measures of inflammation, cellular adhesion, endothelial function, and hemostasis
      in relation to caregiving status, years of caregiving, and major transitions in
      the caregiving situation. RESULTS: During the study period, longer duration of
      caregiving was associated with elevated CRP levels (p = 0.040) and caregivers
      showed greater tumor necrosis factor (TNF)-alpha levels than controls (p =
      0.048). Additionally, 3 months after the death of the AD spouse, caregivers
      showed a significant drop in CRP levels (p = 0.003) and levels of soluble
      intercellular adhesion molecule (sICAM)-1 (p = 0.008). CONCLUSION: Duration of
      caregiving and being a caregiver per se were both associated with chronic low
      grade inflammation as indicated by elevated CRP and TNF-alpha levels,
      respectively. Conversely, death of the AD spouse was associated with lower CRP
      and sICAM-1 levels. The findings indicate that chronic caregiving of those with
      dementia may result in increased inflammation and, thereby, possibly increased
      CVD risk.

PMID- 22133916
TI  - Two fiber genes of nearly equal lengths are a common and distinctive feature of
      Fowl adenovirus C members.
AB  - The complete genome or the genome region containing the two fiber genes of two
      reference strains and one field isolate representing both serotypes of Fowl
      adenovirus C were sequenced. Two fiber genes were revealed in the genomes of all
      three isolates. Fiber-1 and fiber-2 genes of several Fowl adenovirus C isolates
      were sequenced as well. Both serotypes 4 and 10 have two fiber genes. The genome
      region containing the fiber gene was also sequenced for the reference strain of
      Fowl adenovirus B. Just one fiber gene was revealed in this strain. Predicted
      amino acid sequences were compared to already published fiber sequences of
      different adenovirus isolates and one amino acid substitution within fiber-2 was
      detected in all of the Fowl adenovirus C isolates that were isolated from
      chickens with hepatitis-hydropericardium syndrome in comparison to apathogenic
      isolates. Phylogenetic analyses provided insights about the evolution of fiber
      genes in avian adenoviruses and their genetic relationships.

PMID- 22133917
TI  - Size dependence of cavity volume: a molecular dynamics study.
AB  - Partial molar volume, V degrees , has been used as a tool to sample solute
      hydration for decades. The efficacy of volumetric investigations of hydration
      depends on our ability to reliably discriminate between the cavity, V(C), and
      interaction, V(I), contributions to the partial molar volume. The cavity volume,
      V(C), consists of the intrinsic volume, V(M), of a solute molecule and the
      thermal volume, V(T), with the latter representing the volume of the effective
      void created around the solute. In this work, we use molecular dynamics
      simulations in conjunction with the Kirkwood-Buff theory to compute the partial
      molar volumes for organic solutes of varying sizes in water. We perform our
      computations using the Lennard-Jones and Coulombic pair potentials as well as
      truncated potentials which contain only the Lennard-Jones but not the Coulombic
      contribution. The partial molar volume computed with the Lennard-Jones potentials
      in the absence of the Coulombic term nearly coincides with the cavity volume,
      V(C). We determine the thermal volume, V(T), for each compound by subtracting its
      van der Waals volume, V(W), from V(C). Finally, we apply the spherical
      approximation of solute geometry to evaluate the thickness of the thermal volume,
      delta. Our results reveal an increase in the thickness of thermal volume, delta,
      with an increase in the size of the solute. This finding may be related to
      dewetting of large nonpolar solutes and the concomitant increase in the
      compressibility of water of hydration.

PMID- 22133918
TI  - The PP1 phosphatase flapwing regulates the activity of Merlin and Moesin in
      Drosophila.
AB  - The signalling activities of Merlin and Moesin, two closely related members of
      the protein 4.1 Ezrin/Radixin/Moesin family, are regulated by conformational
      changes. These changes are regulated in turn by phosphorylation. The same sterile
      20 kinase-Slik co-regulates Merlin or Moesin activity whereby phosphorylation
      inactivates Merlin, but activates Moesin. Thus, the corresponding coordinate
      activation of Merlin and inactivation of Moesin would require coordinated
      phosphatase activity. We find that Drosophila melanogaster protein phosphatase
      type 1 beta (flapwing) fulfils this role, co-regulating dephosphorylation and
      altered activity of both Merlin and Moesin. Merlin or Moesin are detected in a
      complex with Flapwing both in-vitro and in-vivo. Directed changes in flapwing
      expression result in altered phosphorylation of both Merlin and Moesin. These
      changes in the levels of Merlin and Moesin phosphorylation following reduction of
      flapwing expression are associated with concomitant defects in epithelial
      integrity and increase in apoptosis in developing tissues such as wing imaginal
      discs. Functionally, the defects can be partially recapitulated by over
      expression of proteins that mimic constitutively phosphorylated or
      unphosphorylated Merlin or Moesin. Our results suggest that changes in the
      phosphorylation levels of Merlin and Moesin lead to changes in epithelial
      organization.

PMID- 22133919
TI  - Evaluation of nitrate reduction assay, resazurin microtiter assay and microscopic
      observation drug susceptibility assay for first line antitubercular drug
      susceptibility testing of clinical isolates of M. tuberculosis.
AB  - BACKGROUND: Drug resistant tuberculosis (TB) is a growing concern worldwide.
      Early detection of multidrug-resistant Mycobacterium tuberculosis is of primary
      importance for both patient management and infection control. Optimal method for
      identifying drug-resistant M. tuberculosis in a timely and affordable way in
      resource-limited settings is not yet available. AIM: This study evaluated;
      nitrate reductase assay (NRA), resazurin microtiter assay (REMA) and microscopic
      observation drug susceptibility assay (MODS) against the conventional 1%
      proportion method (PM) for the detection of resistance to first line
      antitubercular drugs, in M. tuberculosis clinical isolates. METHODS: A total of
      one hundred and five clinical isolates of M. tuberculosis; 50 pan sensitive and
      55 pan resistant were tested with NRA, REMA and MODS. The 1% proportion method on
      Lowenstein-Jensen medium was used as reference test. RESULTS: Of all three
      methods which were tested NRA was found to be most sensitive and specific.
      Sensitivity for rifampicin resistance detection was 100%, 94.55% and 92.73% by
      NRA, REMA and MODS respectively. NRA and REMA were found to be 100% specific,
      while the MODS was 98% specific for detection of rifampicin resistance. Test
      results with all these methods were obtained within 8-14 days. CONCLUSION: Rapid
      non-conventional and inexpensive methods may serve as a replacement for 1%
      proportion method in resource limited settings.

PMID- 22133920
TI  - Inhibition of fatty acid amide hydrolase (FAAH) reduces spinal nociceptive
      responses and expression of spinal long-term potentiation (LTP).
AB  - Fatty acid amide hydrolase (FAAH) is an enzyme that metabolizes endocannabinoids
      and fatty acid amides possibly linked to activation of the opioid system. To
      examine how this enzyme affects spinal signalling, electrophysiological
      recordings in the dorsal horn and qPCR on dorsal horn tissue following systemic
      administration of the FAAH inhibitor URB597 (0.3 and 1.0mg/kg i.v.) and spinal
      administration of the opioid receptor antagonist naloxone (0.1 MUg/MUl i.th.),
      were performed. The present data showed that the suppressive effect of the FAAH
      inhibitor URB597 (1.0mg/kg i.v.) on the spinal nociceptive responses was
      prevented by spinal administration of the opioid receptor antagonist naloxone
      (0.1 MUg/MUl i.th.). Moreover, the present findings demonstrated that the FAAH
      inhibitor URB597 (1.0mg/kg i.v.) partly reversed expression of spinal long-term
      potentiation (LTP) and also attenuated the LTP-associated increased Zif
      expression. We conclude that pharmacological inactivation of FAAH may be a
      promising strategy to inhibit the development of central hyperalgesia; thereby
      reinforcing the role of FAAH as a potential therapeutic target.

PMID- 22133921
TI  - Leptin promotes human glioblastoma growth through activating Signal Transducers
      and Activators of Transcription 3 signaling.
AB  - Leptin plays an important role in cancer development and progression. However,
      its role on human glioblastoma cell line U87 growth and the underlying mechanism
      remains unexplored. In this study, we assessed the effect of leptin on U87 cells
      proliferation in vitro and in vivo, elucidating its underlying mechanism. The
      results showed that leptin significantly promoted U87 tumor cells growth in a
      time-and-dose-dependent manner. Leptin increased cell DNA synthesis and promoted
      G(0)/G(1) phase to S phase transition, but without any influence on cell
      apoptosis. In addition, leptin treatment resulted in phosphorylation of Signal
      Transducers and Activators of Transcription 3 (STAT3) on Tyr705, the key
      transcription factor in Janus-Activated Kinase (JAK)/STAT3 signaling pathway. All
      the data suggest that the JAK/STAT3 signaling pathway may be involved in
      promoting U87 glioblastoma growth mediated by leptin, which may be a target for
      anti-neoplastic treatments for glioblastoma.

PMID- 22133922
TI  - Raison d'etre of right ventricle.

PMID- 22133923
TI  - Heart valve prosthesis selection in patients with end-stage renal disease
      requiring dialysis: a systematic review and meta-analysis.

PMID- 22133924
TI  - Which parameter is better to define endothelial dysfunction in a test of
      postocclusive hyperemia measured by laser-Doppler flowmetry?
AB  - BACKGROUND AND OBJECTIVE: Endothelial function can be measured by the level of
      reactive vasodilation due to a transient ischemia caused by a blood pressure cuff
      on the arm, measured using Laser-Doppler flowmetry. This device has software that
      provides various parameters that can measure the magnitude of this response, but
      there are no general agreements with regard to which of them is the best to use.
      In this study, we analyze which of the parameters obtained using this technique
      is better to discriminate between patients with coronary artery disease (CAD) and
      healthy controls. METHODS: We analyzed 40 patients with proven CAD and 60 healthy
      controls. We studied the hyperemic response to the ischemia in the forearm using
      a Laser-Doppler flowmeter. RESULTS: The most important differences between
      patients and controls were determined considering the area of hyperemia, which
      was 2.6 times higher in healthy controls than that in patients (754.9+/-566.4 vs
      1981.3+/-1156.3 perfusion units per second, P<0.001). To diagnose the disease, a
      cutoff point of 860 perfusion units per second had a sensitivity of 0.82 and a
      specificity of 0.97. This is probably because the area of hyperemia measures at
      the same time speed, intensity, and duration of the hyperemic response.
      CONCLUSION: The area of hyperemia was the parameter with a higher sensitivity and
      specificity for identification of patients with CAD. Nevertheless, further
      studies are needed to confirm the usefulness of this parameter, obtained using a
      noninvasive test, to assess the presence of subclinical coronary heart disease.

PMID- 22133925
TI  - Relation of red cell distribution width with the presence, severity, and
      complexity of coronary artery disease.
AB  - OBJECTIVES: Red cell distribution width (RDW) is a measure of the heterogeneity
      of cell size in the peripheral blood and has been shown to be an independent
      correlate of adverse outcomes in healthy participants and in some cardiac
      conditions. We examined the association between RDW and the complexity of
      coronary artery disease (CAD). METHODS: The study population included 193
      nonanemic patients who had undergone coronary angiography for stable angina
      pectoris. Baseline RDW was measured as part of the automated complete blood
      count. Patients were classified depending on whether the SYNTAX score was 0 (no
      angiographically apparent CAD) or at least 1 where CAD was present
      angiographically. RESULTS: Patients with angiographic CAD had significantly
      elevated RDW levels compared with the patients without CAD (14.4+/-1.3 vs. 12.5+/
      0.9, P<0.001). There was a good correlation between RDW and the SYNTAX score
      (r=0.55, P<0.001). In a receiver operating characteristic curve analysis, an RDW
      value of 13.25 was identified as an effective cut-point in the segregation of the
      presence or absence of CAD [area under curve=0.87, 95% confidence interval (CI)
      0.81-0.92]. An RDW value of more than 13.25 yielded a sensitivity of 84%, a
      specificity of 79%, a positive predictive value of 89%, and a negative predictive
      value of 71%. In multivariate analysis, RDW was observed to be an independent
      predictor for both angiographic CAD (odds ratio=4.80, 95% CI 2.41-9.57, P<0.001)
      and for a high (>32) SYNTAX score (odds ratio=2.28, 95% CI 1.45-3.60, P=0.01).
      CONCLUSION: RDW is a readily available clinical laboratory value that is
      associated with both the presence and the complexity of CAD.

PMID- 22133926
TI  - Create the vision.

PMID- 22133927
TI  - Studying the spatial character of the temporomandibular joint.

PMID- 22133928
TI  - How good are you?

PMID- 22133930
TI  - Perplexing relationship between bite force and occlusal contact area.

PMID- 22133931
TI  - Being statistically literate.

PMID- 22133932
TI  - Asymptomatic third molars.

PMID- 22133933
TI  - Are we legally in the right?

PMID- 22133935
TI  - Concern about space for the tongue.

PMID- 22133936
TI  - Silver solder toxicity? Show me the evidence.

PMID- 22133938
TI  - Ethics in orthodontics. When patients are used as currency.

PMID- 22133940
TI  - Associations between sleep-disordered breathing symptoms and facial and dental
      morphometry, assessed with screening examinations.
AB  - INTRODUCTION: Chronic snoring is considered abnormal in a pediatric population.
      This disorder is often attributed to enlarged tonsils and adenoids, but multiple
      anatomic obstructions should also be considered. Facial and dental morphometry
      associations with various sleep-disordered breathing symptoms were investigated
      at an orthodontic clinic. METHODS: Parents or guardians were asked to complete a
      4-part questionnaire on behalf of their children (n = 604; <18 years of age),
      including medical and dental history, bruxism and temporomandibular disorder
      habits, sleep and daytime behavior, and sleep duration and quality. All subjects
      underwent a clinical screening assessment by the same orthodontist to identify
      standard dental, skeletal, functional, and esthetic factors. RESULTS: In contrast
      to sleep-disordered breathing or sleep apnea in adults, which is predominantly
      associated with obesity, sleep-disordered breathing symptoms in this pediatric
      cohort were primarily associated with adenotonsillar hypertrophy, morphologic
      features related to a long and narrow face (dolichofacial, high mandibular plane
      angle, narrow palate, and severe crowding in the maxilla and the mandible),
      allergies, frequent colds, and habitual mouth breathing. CONCLUSIONS: Because of
      the recognized impact of pediatric snoring on children's health, the
      determination of these good predictors can help in preventing and managing sleep
      disordered breathing. If a health professional notices signs and symptoms of
      sleep-disordered breathing, the young patient should be referred to a sleep
      medicine specialist in conjunction with an orthodontist if there are
      dentoskeletal abnormalities.

PMID- 22133941
TI  - Space changes after premature loss of deciduous molars among Brazilian children.
AB  - INTRODUCTION: The use of space maintainers after the premature loss of deciduous
      molars is routine in pediatric dentistry. However, there is a need for evidence
      offering a better scientific basis for prescribing these appliances. In this
      study, we aimed to assess dimensional changes in the dental arches after the
      premature loss of deciduous molars. METHODS: A sample of 55 children between 6
      and 9 years of age with unilateral loss of either first or second molars was
      followed for 10 months by clinical examination, cast analysis, and radiographic
      analysis. The space in the extraction site, arch length, and hemi-perimeter of
      the extraction and control sides were measured. Intraexaminer agreement was high
      (0.990). The data were analyzed by using the F test (analysis of variance),
      Bonferroni test, least significant difference, and Student t test. RESULTS: Only
      the group of children with premature loss of the mandibular second deciduous
      molars exhibited significant dimensional alterations during the follow-up.
      CONCLUSIONS: The findings emphasize a need for the judicious indication for space
      maintainers. The major effect on the dental arches occurred in the first 3 months
      after the extraction of the deciduous molars, indicating that these appliances
      should be fitted during this period.

PMID- 22133942
TI  - Release of bisphenol A from resin composite used to bond orthodontic lingual
      retainers.
AB  - INTRODUCTION: In this study, we assessed the changes in bisphenol A (BPA) levels
      in saliva and urine after placing lingual bonded retainers. METHODS: Liquid
      chromatography/mass spectrometry was used to examine the BPA levels in the saliva
      and urine samples collected from 22 volunteers who received a lingual bonded
      retainer on their mandibular dentition. Samples were collected immediately before
      placement and 30 minutes, 1 day, 1 week, and 1 month after placement. The time
      elapsed after placement, type of resin composite (nanohybrid filled flowable
      resin or conventional hybrid resin), surface prophylaxis, age, and sex were
      evaluated for their effects on the BPA levels. RESULTS: The only significant high
      level of BPA was observed in the saliva collected just after placement of the
      lingual bonded retainer. Age and sex did not affect the BPA levels. Subjects in
      the flowable resin group had lower BPA levels than those in the conventional
      hybrid resin group; pumice prophylaxis decreased the level of BPA released from
      the conventional hybrid resin at the immediate time point. The salivary BPA level
      (maximum, 20.889 ng/mL) detected in the samples collected just after placement
      was far lower than the reference daily intake dose. CONCLUSIONS: Accordingly, the
      potential toxicity of BPA from placing lingual bonded retainer might be
      negligible. On the other hand, because the health-effective amount of BPA is
      controversial, BPA release should be minimized.

PMID- 22133944
TI  - In-vitro and in-vivo study of periodontal ligament cryopreserved with a magnetic
      field.
AB  - INTRODUCTION: The purpose of this study was to examine the effect of a new
      cryopreservation method with a magnetic field on periodontal regeneration in
      vitro and in vivo. METHODS: Human periodontal ligament cells were frozen in 10%
      dimethyl sulfoxide by using a programmed freezer with a magnetic field. Cells
      were cryopreserved for 3 days at -150 degrees C. Immediately after thawing,
      collagen type I and alkaline phosphatase gene expression were determined by real
      time polymerase chain reaction. Incisors were extracted from 15-week-old Wistar
      rats and cryopreserved or dried for 3 days. Then the incisors were replanted into
      the same sockets. Ninety days after transplantation, they were observed under
      light microscopy. RESULTS: There was no difference in the messenger RNA
      expression of collagen type I between the cryopreserved and the control groups.
      The expression of alkaline phosphatase messenger RNA in the cryopreserved group
      was slightly decreased compared with the control group. There was no progressive
      root resorption in the teeth that were replanted immediately (control group) or
      cryopreserved. However, there was widespread root resorption and ankylosis in the
      dried teeth. CONCLUSIONS: These results show that a magnetic field programmed
      freezer can be successfully used for cryopreservation of teeth.

PMID- 22133945
TI  - Cortical bone thickness and bone depth of the posterior palatal alveolar process
      for mini-implant insertion in adults.
AB  - INTRODUCTION: Cortical bone thickness and bone depth are important factors when
      placing an orthodontic mini-implant. The objective of this study was to
      investigate both variables for the palatal alveolar process. METHODS: Thirty dry
      human skulls were imaged by using cone-beam computed tomography technology. Two
      dimensional slices bisecting the posterior interdental sites were generated, and
      cortical bone thickness and bone depth were measured at 4, 8, and 12 mm from the
      alveolar crest. Two-way repeated measures analysis of variance (ANOVA) was used
      to analyze the measurements. RESULTS: Interdental site and measurement level had
      a significant impact on both cortical bone thickness and bone depth. Cortical
      bone thickness was typically greatest at the 8-mm measurement level and more
      anterior interdental sites. Bone depth decreased with higher measurement levels
      and was smallest at the most posterior-superior measurement points. CONCLUSIONS:
      Cortical bone thickness and bone depth of the palatal alveolar process are, on
      average, favorable for the insertion of orthodontic mini-implants; however, some
      sites should routinely be avoided to prevent damage to the maxillary sinus unless
      3-dimensional imaging is available.

PMID- 22133943
TI  - Three-dimensional assessment of maxillary changes associated with bone anchored
      maxillary protraction.
AB  - INTRODUCTION: Bone-anchored maxillary protraction has been shown to be an
      effective treatment modality for the correction of Class III malocclusions. The
      purpose of this study was to evaluate 3-dimensional changes in the maxilla, the
      surrounding hard and soft tissues, and the circummaxillary sutures after bone
      anchored maxillary protraction treatment. METHODS: Twenty-five consecutive
      skeletal Class III patients between the ages of 9 and 13 years (mean, 11.10 +/-
      1.1 years) were treated with Class III intermaxillary elastics and bilateral
      miniplates (2 in the infrazygomatic crests of the maxilla and 2 in the anterior
      mandible). Cone-beam computed tomographs were taken before initial loading and 1
      year out. Three-dimensional models were generated from the tomographs, registered
      on the anterior cranial base, superimposed, and analyzed by using color maps.
      RESULTS: The maxilla showed a mean forward displacement of 3.7 mm, and the
      zygomas and the maxillary incisors came forward 3.7 and 4.3 mm, respectively.
      CONCLUSIONS: This treatment approach produced significant orthopedic changes in
      the maxilla and the zygomas in growing Class III patients.

PMID- 22133946
TI  - Association between dental floss use and gingival conditions in orthodontic
      patients.
AB  - INTRODUCTION: Evidence comparing periodontal conditions in orthodontic patients
      who regularly use or do not use dental floss is scarce. METHODS: The subjects
      were 330 patients who had been under fixed orthodontic treatment for at least 6
      months. They were examined by 1 calibrated examiner for plaque and gingival
      indexes, probing pocket depths, clinical attachment losses, and excessive resin
      around brackets. Socioeconomic background, time with orthodontic appliances, and
      use of dental floss were assessed in interviews. Unadjusted and multiple logistic
      regression analyses were used to assess the associations. RESULTS: The results
      demonstrated statistically significant higher means of plaque index, gingival
      index, pocket probing depth, and clinical attachment loss for nonusers of dental
      floss. Intragroup analyses showed higher means of these parameters in proximal
      sites and posterior teeth, compared with their counterparts' buccal and lingual
      sites and anterior teeth, respectively. After multivariate analysis, male
      subjects (P = 0.044) with a household income less than 5 national minimum wages
      (P = 0.044), and nonusers of dental floss (P = 0.000) showed higher probabilities
      of gingival bleeding (>30%) than did their counterparts. CONCLUSIONS: Orthodontic
      patients who use dental floss regularly have somewhat better gingival conditions
      than those who do not use floss.

PMID- 22133947
TI  - Applicant selection procedures for orthodontic specialty programs in the United
      States: survey of program directors.
AB  - INTRODUCTION: With the recent changes in scoring of the National Board Dental
      Examinations and grading systems in some dental schools, ranking prospective
      orthodontic applicants has become a challenge. METHODS: A 31-item survey was sent
      to orthodontic program directors in the United States to determine admission
      practices of all accredited specialty orthodontic programs. RESULTS: Forty-four
      of 64 program directors responded (69%). This study showed a wide variation of
      admission practices among these programs. The only consistent part of admissions
      in all programs was the interview process. The top factors considered for each
      applicant were interview ratings, dental school class rank, and letters of
      recommendation. The top sources of recommendations were the orthodontic
      department chair, the graduate program director, and the predoctoral orthodontic
      program director. The top 3 character traits considered most favorable were
      maturity, and good verbal and listening skills. CONCLUSIONS: Accredited
      orthodontic programs in the United States follow different procedures in
      assessing applicants for admission. It is important to consider both academic and
      nonacademic measures in assessing applicant information in a standardized manner
      to ensure a fair and efficient selection process.

PMID- 22133948
TI  - Transverse maxillary arch form and mandibular asymmetry in patients with
      posterior unilateral crossbite.
AB  - INTRODUCTION: Posterior unilateral crossbite treatment is usually oriented to the
      maxilla. The aims of this retrospective investigation were (1) to study the
      maxillary arch morphology in patients with posterior unilateral crossbite and (2)
      to evaluate the possible association between the transverse maxillary arch
      morphology and the skeletal symmetry or asymmetry of the corresponding mandible.
      METHODS: Data from maxillary arch occlusograms and posteroanterior and panoramic
      radiograph tracings of the mandible were obtained for 94 patients with posterior
      unilateral crossbite and midline deviation. A multiple linear regression model
      was used to assess the association of transverse maxillary arch morphology with
      demographic and clinical characteristics. The prevalence of skeletal asymmetry
      was modeled by using a multiple logistic regression on transverse maxillary arch
      morphology, adjusted for the patients' characteristics. RESULTS: Three maxillary
      arch morphologies were found at the crossbite side: symmetric, contracted, and
      expanded. The expanded crossbite sides were statistically associated with
      mandibular asymmetry. CONCLUSIONS: Different transverse maxillary arch forms at
      the crossbite side were observed in our patients with posterior unilateral
      crossbite. This finding might be interpreted as a diagnostic and prognostic key
      for mandibular asymmetry, paving the way for new treatment directions.

PMID- 22133949
TI  - Differences in craniofacial and dental characteristics of adolescent Mexican
      Americans and European Americans.
AB  - INTRODUCTION: The purpose of this study was to compare the soft-tissue profiles
      of matched Class I adolescent European Americans and Mexican Americans. The
      secondary aim was to explain profile differences based on group differences in
      soft-tissue thickness, skeletal morphology, dental position, and tooth size.
      METHODS: The study pertained to 207 untreated Class I adolescents, including 93
      Mexican Americans and 114 European Americans. Lateral cephalometric and model
      analyses were performed to quantify morphologic differences. Two-way analyses of
      variance were used to evaluate ethnicity, sex, and their interaction. RESULTS:
      Mexican Americans had significantly (P <0.05) greater lip protrusion and facial
      convexity than did European Americans. Mexican Americans had smaller craniofacial
      dimensions and larger teeth, resulting in maxillary and mandibular dentoalveolar
      protrusion. Mexican Americans also had thicker soft tissues and greater maxillary
      skeletal prognathism than European Americans. The combination of thicker soft
      tissues, maxillary skeletal prognathism, and dentoalveolar protrusion explained
      the protrusive lips of Mexican Americans. The greater facial convexity of Mexican
      Americans was due primarily to maxillary prognathism and mandibular
      hyperdivergence. Sex differences pertained primarily to size; the linear
      dimensions of the boys were consistently and significantly larger than those of
      the girls. CONCLUSIONS: European American normative data and treatment objectives
      do not apply to Mexican Americans. Knowledge of the soft-tissue, skeletal
      morphology, and dental position differences should be applied when planning
      treatment for Mexican American patients.

PMID- 22133950
TI  - Dental age assessment in patients with maxillary canine displacement.
AB  - INTRODUCTION: The aims of this study were to investigate the relationship between
      dental age and maxillary canine displacement with 2 methods, to study differences
      in dental development between the displaced and nondisplaced sides, and to
      investigate sex differences in dental development in the studied groups. METHODS:
      Two hundred forty subjects were recruited for this study. They were divided into
      2 groups: the palatally displaced canine group (87 girls, 33 boys) and the
      buccally displaced canine group (81 girls, 39 boys). Dental ages were assessed by
      using the 2 methods. RESULTS: Delayed dental development was associated with
      subjects with palatally displaced canines only, whereas those with buccally
      displaced canines had comparable dental development to that of the control group.
      Sex differences in the 3 groups were found; girls had more pronounced delayed
      dental development in all groups according to both methods. With unilateral
      palatally displaced canines, the displacement side showed delayed dental
      development compared with the side of nondisplacement (P = 0.002). The
      development rates of the displaced and nondisplaced sides were comparable in the
      subjects with unilateral buccally displaced canines. CONCLUSIONS: Palatal and
      buccal canine displacements are 2 distinct entities; delayed dental development
      plays a role in the etiology of palatal canine displacement, but not in buccal
      canine displacement.

PMID- 22133951
TI  - Patterns of third-molar agenesis and associated dental anomalies in an
      orthodontic population.
AB  - INTRODUCTION: The aim of this study was to investigate the frequency of dental
      anomalies in orthodontic patients with different patterns of third-molar
      agenesis, comparing them with patients without third-molar agenesis. METHODS: A
      sample of 374 patients with agenesis of at least 1 third molar was divided into 4
      groups according to the third-molar agenesis pattern, and a control group of 98
      patients without third-molar agenesis was randomly selected from the patient
      archives. Panoramic radiographs and cast models were used to determine the
      associated dental anomalies, such as hypodontia, hyperdontia, impaction,
      dilaceration, microdontia, ectopic eruption, transposition, and transmigration.
      The Pearson chi-square and Fisher exact tests were used to determine the
      differences in the distribution of the associated dental anomalies among the
      groups. RESULTS: The prevalence of agenesis of other teeth (11.2%, n = 42) was
      significantly greater in our study sample (groups 1-4) than in the control group
      (group 5) (4.1%, n = 4; P <0.05). When we compared the groups according to the
      various third-molar agenesis patterns, we found that agenesis of other teeth was
      more common in patients with agenesis of 3 and 4 third molars. In addition, the
      patients with agenesis of 4 third molars exhibited maxillary lateral-incisor
      microdontia more frequently. Another important finding was a higher prevalence of
      total dental anomalies in patients with agenesis of 3 and 4 third molars compared
      with the control group. CONCLUSIONS: Permanent tooth agenesis, microdontia of
      maxillary lateral incisors, and total dental anomalies are more frequently
      associated with agenesis of 4 third molars than with the presence of third
      molars.

PMID- 22133952
TI  - Nonsurgical treatment of a Class III patient with a lateral open-bite
      malocclusion.
AB  - A 15.3-year-old white girl with a skeletal Class III malocclusion and a severe
      lateral open bite was treated with conventional orthodontics and directional
      force mechanics and elastics. She had 5 congenitally missing premolars. The
      maxillary right canine was ectopically erupted and in contact with the maxillary
      right first molar. An Angle Class I molar relationship was achieved with canine
      protected occlusion and incisal guidance. A wrap-around retainer was placed on
      the maxillary arch and a lingual bonded retainer on the mandibular arch.
      Treatment time was 38 months.

PMID- 22133953
TI  - Treatment of an adult with several missing teeth and atrophic old mandibular
      first molar extraction sites.
AB  - This report describes the orthodontic treatment of a woman, aged 34 years 2
      months, with several missing teeth and atrophic mandibular first molar extraction
      sites. We had planned to close the spaces from the missing maxillary canines with
      mesial movement of the premolars and molars. In the mandibular arch, protraction
      of the second molars into first molar extraction sites and reduction of the
      mandibular incisor protrusion were performed. No miniscrews or bone plates were
      used. A modified helical loop was used, and it can be considered a simple and an
      efficient orthodontic method of closing the spaces without mesial or lingual
      tipping and rotation. Pleasing esthetic and functional results were achieved.

PMID- 22133954
TI  - Control of maxillary dentition with 2 midpalatal orthodontic miniscrews.
AB  - The midpalatal area has no critical anatomic structures and has thick cortical
      bone. These conditions are favorable for miniscrew implantation. Also, there is
      no concern that damaging a dental root in this area would cause failure of the
      miniscrew. Although these advantages can decrease the failure rate of miniscrews,
      midpalatal miniscrews have not been as popular as interdental miniscrews. Because
      the midpalatal area is far from the teeth, the utility of midpalatal miniscrews
      has been considered to be limited. This article describes a new method for
      controlling the maxillary dentition with 2 midpalatal miniscrews.

PMID- 22133955
TI  - Combined 3-dimensional and mirror-image analysis for the diagnosis of asymmetry.
AB  - Three-dimensional imaging techniques have greatly improved our ability to assess
      asymmetry by means of linear and angular measurements. However, visualizing
      deformities enables a unique appreciation of the underlying deformity, which
      might not be possible by looking at quantitative numbers alone. This article
      describes the method of a mirror-image analysis technique to visualize the
      asymmetry to assist in diagnosis and treatment planning. Other advantages of a
      mirror-image analysis, in addition to the quantitative analysis, are also
      discussed.

PMID- 22133956
TI  - Faces in 4 dimensions: Why do we care, and why the fourth dimension?
AB  - The purpose of this article is to describe a dynamic approach for 3-dimensional
      analyses of facial soft-tissue movements. The method and analysis have numerous
      applications but, most specifically, are used to assess diagnostic and treatment
      outcomes of soft-tissue surgery in patients with repaired cleft lip and palate.

PMID- 22133957
TI  - Litigation and legislation. Failing the ABO examination: admissible evidence?

PMID- 22133958
TI  - Randomization. Part 2: Minimization.

PMID- 22133959
TI  - Treatment outcome analysis of speedy surgical orthodontics for adults with
      maxillary protrusion.
AB  - INTRODUCTION: The purposes of this study were to quantify the treatment outcomes
      of speedy surgical orthodontic treatment for adults with maxillary protrusion and
      to identify the key factors influencing the efficacy of speedy surgical
      orthodontic biomechanics. METHODS: Twenty-four adults with maxillary or
      bimaxillary protrusion were treated with speedy surgical orthodontics, including
      maxillary perisegmental corticotomy followed by the orthopedic en-masse
      retraction against C-palatal miniplate anchorage. The average total treatment
      time was 20 months (range, 11-42 months). Lateral cephalograms were taken at
      pretreatment, just after the perisegmental corticotomy, and at posttreatment to
      evaluate the skeletal and soft-tissue changes. The Pearson correlation analysis
      was used to identify the relationships between hard-tissue, soft-tissue, and
      perisegmental corticotomy variables. RESULTS: The maxillary central incisors were
      retracted by 9.19 +/- 0.31 mm and retroclined by 19.73 degrees  +/- 1.17 degrees
      . The change of the maxillary alveolar ridge angle was 13.97 degrees  +/- 1.04
      degrees . The extrusion tendency of the retracted maxillary incisors was minimal,
      measured as 1.17 +/- 0.36 mm. The width of the buccal corticotomy showed
      statistically significant correlations with the angular change of the maxillary
      central incisors and the maxillary alveolar ridge angle. The retrusion of the
      maxillary central incisors and the maxillary alveolar ridge angle were the 2 hard
      tissue variables that most closely correlated with retrusion of the upper lip.
      CONCLUSIONS: Speedy surgical orthodontic treatment can be an effective modality
      for adults with severe maxillary protrusion.

PMID- 22133960
TI  - Assessment of motivation and psychological characteristics of adult orthodontic
      patients.
AB  - INTRODUCTION: In recent years, the demand for adult orthodontic treatment has
      grown rapidly; yet there is a paucity of information on this subgroup of
      patients. It is well known that understanding the psychological characteristics
      and motives of any patient is fundamental and that these factors might affect
      patient satisfaction and adherence with treatment. There is therefore a need for
      clinicians to improve their understanding of this subgroup to enhance the
      patient's experience of treatment delivery and to increase the potential for a
      successful treatment outcome. The aim of this study was to develop a measure for
      the assessment of motivating factors and psychological characteristics of adults
      seeking orthodontic treatment. METHODS: This study involved the qualitative
      development of a valid patient-centered questionnaire to assess motivating
      factors for adults seeking orthodontic treatment. This was achieved through semi
      structured in-depth interviews; key themes were identified and used to construct
      a questionnaire assessing motivation for treatment. This was then combined with 3
      previously validated questionnaires to measure self-esteem, anxiety or
      depression, and body image and facial body image. The questionnaire was
      distributed to 172 adult orthodontic patients at different stages of treatment in
      a large teaching hospital in the United Kingdom. In addition, the self-esteem,
      body image, and facial body image scores were compared with data on orthognathic
      patients from the same hospital and with data from members of the general public.
      RESULTS: Desire to straighten the teeth and improve the smile were the key
      motivating factors for the adult group studied. Other motives included to improve
      the bite, improve facial appearance, and close (dental) spacing. With respect to
      the psychological characteristics of self-esteem, body image, and facial body
      image, the adult orthodontic group was comparable with the general public.
      However, differences were noted when comparing data from the adult orthodontic
      group with previously collected data on orthognathic patients. CONCLUSIONS: The
      motives for adults to seek orthodontic treatment are numerous and varied, whereas
      psychological traits appear to be closer to those of the general public than to
      orthognathic patients.

PMID- 22133961
TI  - Changes in stress distribution of orthodontic miniscrews and surrounding bone
      evaluated by 3-dimensional finite element analysis.
AB  - INTRODUCTION: Miniscrews can be used to provide absolute anchorage during
      orthodontic treatment. If we could obtain the optimum design or shape of the
      miniscrew, we might be able to reduce its size and lessen the chance of root
      contact. In addition, miniscrews are placed at several angles, and orthodontic
      forces are applied in various directions for clinical requirements. In this
      study, we used finite element analysis to investigate changes in stress
      distribution at the supporting bone and miniscrew by changing the angle and the
      shape of the miniscrew and the direction of force. METHODS: Three types of
      miniscrews (cylindrical pin, helical thread, and nonhelical thread) were designed
      and placed in 2 types of supporting bone (cancellous and cortical). The
      miniscrews were inclined at 30 degrees , 40 degrees , 45 degrees , 50 degrees ,
      60 degrees , 70 degrees , 80 degrees , and 90 degrees  to the surface of the
      supporting bone. A force of 2N was applied in 3 directions. RESULTS:
      Significantly lower maximum stress was observed in the cancellous bone compared
      with the cortical bone. By changing the implantation angle, the ranges of the
      maximum stress distribution at the supporting bone were 9.46 to 14.8 MPa in the
      pin type, and 17.8 to 75.2 MPa in the helical thread type. On the other hand, the
      ranges of the maximum stress distribution at the titanium element were 26.8 to
      92.8 MPa in the pin type, and 121 to 382 MPa in the helical thread type.
      According to the migration length of the threads in the nonhelical type, the
      maximum stresses were 19.9 to 113 MPa at the bone, and 151 to 313 MPa at the
      titanium element. By changing the angle of rotation in the helical thread type,
      the maximum stress distributions were 25.4 to 125 MPa at the bone, and 149 to 426
      MPa at the titanium element. Furthermore, the maximum stress varied at each angle
      according to the direction of the applied load. CONCLUSIONS: From our results,
      the maximum stresses observed in all analyzed types and shapes of miniscrews were
      under the yield stress of pure titanium and cortical bone. This indicates that
      the miniscrews in this study have enough strength to resist most orthodontic
      loads.

PMID- 22133962
TI  - Gram-negative periodontal pathogens and bacterial endotoxin in metallic
      orthodontic brackets with or without an antimicrobial agent: an in-vivo study.
AB  - INTRODUCTION: High levels of periodontal pathogens can cause periodontal
      alterations. The presence of endotoxin might be responsible for the occurrence
      and progression of tissue inflammation and bone resorption. The aims of this
      study were to use checkerboard DNA-DNA hybridization and limulus amebocyte lysate
      assay to evaluate in metallic orthodontic brackets (1) the presence of 16 gram
      negative periodontal pathogenic microorganisms of the orange complex and red
      complex +Treponema socranskii, (2) the amount of bacterial endotoxin, and (3) the
      efficacy of 0.12% chlorhexidine gluconate mouthwash in reducing bacterial
      contamination and endotoxin amount. METHODS: Thirty-three patients (ages, 11-33
      years) under orthodontic treatment with fixed appliances had 3 new metallic
      brackets bonded to 3 different premolars. Sixteen patients used a 0.12%
      chlorhexidine gluconate mouthwash (Periogard, Colgate-Palmolive, Sao Bernardo do
      Campo, Sao Paulo, Brazil) (experimental group), and 17 patients used a placebo
      mouthwash (control group) twice a week. After 30 days, the brackets were removed,
      and the samples were obtained. The data were analyzed statistically by Mann
      Whitney, Kruskal-Wallis, and Dunn tests (alpha = 0.05). RESULTS: The 0.12%
      chlorhexidine gluconate group accumulated significantly lower levels of
      microorganisms than did the placebo group (P = 0.01). When each microbial complex
      was analyzed separately, a statistically significant difference between the
      experimental and control groups was found for the orange complex (P = 0.04). A
      greater amount of bacterial endotoxin was detected in the 0.12% chlorhexidine
      gluconate group than in the control group (P = 0.02). CONCLUSIONS: The 0.12%
      chlorhexidine gluconate oral rinses can be useful to reduce the levels of gram
      negative periodontal pathogenic microorganisms in patients with fixed orthodontic
      appliances. Considering the increased amount of bacterial endotoxin after
      chlorhexidine gluconate use, further research is necessary to develop clinical
      procedures or antimicrobial agents with action against bacterial endotoxin
      adhering to metallic brackets.

PMID- 22133963
TI  - Landmark identification errors on cone-beam computed tomography-derived
      cephalograms and conventional digital cephalograms.
AB  - INTRODUCTION: In this study, we investigated the landmark identification errors
      on cone-beam computed tomography (CBCT)-derived cephalograms and conventional
      digital cephalograms. METHODS: Twenty patients who had both a CBCT-derived
      cephalogram and a conventional digital cephalogram were recruited. Twenty
      commonly used lateral cephalometric landmarks and 2 fiducial points were
      identified on each cephalogram by 11 observers at 2 time points. The mean
      positions of the landmarks identified by all observers were used as the best
      estimate to calculate the landmark identification errors. In addition to
      univariate analysis, regression analysis of landmark identification errors was
      conducted for identifying the predicting variables of the observed landmark
      identification errors. To properly handle the multilayer correlations among the
      clustered observations, a marginal multiple linear regression model was fitted to
      our correlated data by using the well-known generalized estimating equations
      method. In addition to image modality, many variables potentially affecting
      landmark identification errors were considered, including location and
      characteristics of the landmark, seniority of the observer, and patient
      information (sex, age, metallic dental restorations, and facial asymmetry).
      RESULTS: Image modality was not the significant variable in the final generalized
      estimating equations model. The regression coefficient estimates of the
      significant landmarks for the overall identification error ranged from -0.99 (Or)
      to 1.42 mm (Ba). The difficulty of identifying landmarks on structural images
      with multiple overlapping--eg, Or, U1R, L1R, Po, Ba, UMo, and LMo--increased the
      identification error by 1.17 mm. In the CBCT modality, the identification errors
      significantly decreased at Ba (-0.76 mm). CONCLUSIONS: The overall landmark
      identification errors on CBCT-derived cephalograms were comparable to those on
      conventional digital cephalograms, and Ba was more reliable on CBCT-derived
      cephalograms.

PMID- 22133964
TI  - Physical properties of root cementum: part 21. Extent of root resorption after
      the application of 2.5 degrees  and 15 degrees  tips for 4 weeks: a microcomputed
      tomography study.
AB  - INTRODUCTION: Microcomputed tomography offers a unique opportunity to accurately
      examine orthodontically induced inflammatory root resorption. The aims of this
      study were to quantify, in 3 dimensions, the amount of root resorption caused by
      placing heavy and light distal root tipping forces on premolars and to compare
      the prevalence of root resorption in different areas of the tooth. METHODS:
      Thirty maxillary first premolars from 15 patients who were to have these teeth
      extracted as part of their orthodontic treatment were selected for this study.
      Each tooth in the same patient was randomly chosen to have either a 2.5 degrees 
      or a 15 degrees  distal root tipping bend placed for 4 weeks. After the
      experimental period, the teeth were extracted according to a strict protocol to
      prevent damage to the root. They were then imaged by a microcomputed tomography
      scan x-ray system (SkyScan 1172, SkyScan, Aartselaar, Belgium) and analyzed by
      software designed for volumetric measurements. RESULTS: A significant difference
      was found in the amount of total root resorption between light and heavy forces
      (P = .021). The mean cube root volumes of the resorption craters in the 15
      degrees  tip-bend group were greater than in the 2.5 degrees  tip-bend group.
      This significance was lost when the tooth was divided into vertical thirds,
      although a trend was still present. When the areas of expected compression in the
      periodontal ligament were compared with the areas of expected tension,
      significance was seen in the apical and cervical thirds only. CONCLUSIONS: Based
      on this experiment, one can conclude that a 15 degrees  distal root tip bend
      causes more orthodontically induced inflammatory root resorption than a 2.5
      degrees  distal root tip bend. Furthermore, greater root resorption was found in
      areas under pressure when compared with areas under tension.

PMID- 22133965
TI  - Clinical significance of micrometastases in lymph nodes from laryngeal squamous
      cell carcinoma.
AB  - OBJECTIVE: To assess the role of lymph nodes micrometastases in laryngeal
      squamous cell carcinoma and correlate the results with survival. METHODS: We
      performed immunohistochemical analyses of lymph nodes after the resection of 126
      patients for detection of micrometastasis. The lymph nodes were examined with
      hematoxylin and eosin (HE)-stained and cytokeratin (CK) antibodies AE1/AE3
      stained. Recurrences and metastases were recorded during follow-up. The Kaplan
      Meier method was used for survival analysis. RESULTS: In total, 126 patients
      underwent neck dissection. Forty-one patients were HE positive (group 1), while
      85 were HE negative. Thirty-three of these HE negative patients were CK positive
      (group 2), while 52 were CK negative (group 3). Patients in groups 2 and 3 had a
      different outcome (P < .001). Survival was worse in patients in group 2 (10-year
      survival of 52.12% vs 81.16% in group 3, P < .01). CONCLUSION:
      Immunohistochemical analysis is an efficient way to detect micrometastasis in
      lymph nodes after the resection of conventionally node-negative patients. The
      detection of CK-positive cells is an independent prognostic factor, and more
      aggressive treatment should be indicated in these patients.

PMID- 22133966
TI  - Sphenoid sinus barotrauma after scuba diving.
AB  - We report the case of an 18-year-old male patient operated on for sphenoid sinus
      barotrauma after scuba diving. The patient attended our emergency department
      because of intractable headache but did not improve with conservative treatment.
      After computed tomography and magnetic resonance imaging examination, he was
      diagnosed with sphenoid sinusitis that extended to the nasal septum. He therefore
      underwent surgery for sinus ventilation and abscess drainage.

PMID- 22133967
TI  - Transoral robotic surgery for supraglottic squamous cell carcinoma.
AB  - PURPOSE: We present our experience with the use of transoral robotic surgery
      (TORS) for treatment of supraglottic squamous cell carcinoma. MATERIALS AND
      METHODS: We studied all patients who underwent TORS for supraglottic squamous
      cell carcinoma, with or without adjuvant therapy, from March 2007 through June
      2009, who had a minimum of 2 years of follow-up. Primary functional outcomes
      included dysphonia, tracheostomy dependence, and gastrostomy tube dependence.
      Disease control and survival were estimated with the Kaplan-Meier method.
      RESULTS: Of 9 patients in the study group, 7 (78%) had advanced-stage disease.
      All 9 patients had negative margins after TORS, with no perioperative
      complications. Regional recurrence and local recurrence developed in 1 patient
      each. One patient died of disease. At last follow-up, 7 patients (78%) were
      tracheostomy free, and 7 (78%) were gastrostomy tube free. CONCLUSIONS: Transoral
      robotic surgery is a promising modality for resection of supraglottic squamous
      cell carcinoma. Transoral robotic surgery achieved functional laryngeal
      preservation in most patients with no complications.

PMID- 22133968
TI  - Preauricular sinus: advantage of the drainless minimal supra-auricular approach.
AB  - OBJECTIVES: We performed this study to introduce our minimal supra-auricular
      approach for the surgical management of a preauricular sinus (PAS) and to
      evaluate the advantages of this drainless technique. STUDY DESIGN: This was a
      retrospective study. SETTING: The study was done in a tertiary referral center.
      METHODS: We enrolled 94 patients (101 ears) with a PAS who underwent surgical
      treatment via a minimal supra-auricular approach performed by one surgeon between
      April 1999 and May 2010. After removing the specimen, meticulous subcutaneous
      suturing and no drain were used in 83 patients (89 ears) and a postoperative
      drain was inserted in 11 patients (12 ears). Surgical outcomes of this technique
      were compared between the groups with and without postoperative drain insertion.
      RESULTS: With a good surgical view and meticulous subcutaneous mattress sutures
      in our minimal supra-auricular approach for PAS excision, there was no
      postoperative recurrence or other serious complication. In the drain group,
      previous operation history was more frequent (P = .010), and the rate of
      preoperative infection was higher than in the drainless group (P = .018).
      Postoperatively, a compression dressing was required more frequently (P = .002)
      and for longer in the drain group (P = .001). The rate of immediate postoperative
      wound infection was higher in the drain group (P = .003). CONCLUSION: Our
      drainless minimal supra-auricular approach for the surgical removal of a PAS has
      advantage in terms of good surgical results of no recurrence and is more
      comfortable for patients because of the reduced need for a compression dressing.
      We suggest that this technique is effective and safe for PAS excision.

PMID- 22133969
TI  - Recognition and management of perioperative serotonin syndrome.
AB  - Mild forms of serotonin syndrome can potentially be fatal, if not recognized. The
      increased use of serotonergic agents makes the awareness of its prevalence,
      various presentations, diagnostic evaluation, and treatment a clinical
      imperative. It is important to note that serotonin syndrome can only be diagnosed
      clinically in the presence of 3 clinical criteria: mental status changes,
      autonomic manifestations, and neuromuscular abnormalities. This case report
      describes a patient who underwent an uncomplicated closed nasal fracture
      reduction and subsequently developed serotonin syndrome.

PMID- 22133970
TI  - Assessment of cochlear and auditory pathways in patients with migraine.
AB  - PURPOSE: In this study, we aimed to determine the function of the cochlea and
      peripheral and central auditory pathways with migraine. MATERIALS AND METHODS:
      Fifty-eight patients with migraine and 40 healthy subjects were assessed using
      routine diagnostic audiometry along with transient evoked otoacoustic emissions
      (TOAEs), distortion product otoacoustic emissions (DPOAEs), and auditory
      brainstem response (ABR) at high and low repetition rate frequencies. RESULTS:
      Nearly two thirds of patients with migraine had one or more abnormalities in
      electrophysiological testing. Compared with control subjects, patients reported
      significant lowering of TOAEs amplitude at frequencies of 1 kHz (right: P =
      .0003; left: P = .002), 3 kHz (right: P = .025), and 4 kHz (right: P = .019);
      prolonged wave III latency (right: P = .009); and I-V interpeak latency (IPL)
      (left: P = .024) at high repetition rate frequencies. Significant correlations
      were identified between age, duration of illness and frequency of migraine and
      TOAEs total response and at amplitude of 4 kHz, amplitudes of DPOAEs at 1, 1.5,
      2, 3, and 5 kHz and I, III and wave latencies and I-V IPL of ABR at high rate
      frequencies. CONCLUSIONS: These data suggest that subclinical changes in cochlear
      function and auditory pathways are associated with chronic migraine. It is
      possible that migraine could be accompanied by compromise of blood supply of
      auditory system.

PMID- 22133971
TI  - Dichotic listening test in patients with chronic cerebellar disease.
AB  - PURPOSE: The aim of the study was to identify alterations in the auditory
      processing of patients with chronic cerebellar disease using a dichotic listening
      test with alternating dissyllables, also known as the Staggered Spondaic Word
      (SSW) test. MATERIALS AND METHODS: A study involving a control group of 20
      subjects and a study group of 18 patients with chronic cerebellar disease of both
      sexes aged between 9 and 56 years was performed. The SSW test was conducted in
      accordance with strict standard protocols along with the analysis procedures.
      RESULTS: Findings revealed a statistically significant difference in the
      quantitative alterations on the SSW test in the study group compared with the
      control group (P < .001). Results of the qualitative evaluation showed no
      statistically significant differences between the study and control groups for
      order or auditory effects. However, a statistically significant difference for
      presence of inversions was identified, with the worse result in the study group.
      CONCLUSION: The present study identified quantitative and qualitative changes in
      auditory processing for decodifying, gradual memory loss, and organization modes
      on the dichotic listening test with alternating dissyllables (SSW) in individuals
      with chronic cerebellar disease.

PMID- 22133972
TI  - The formation of zona radiata in Pseudosciaena crocea revealed by light and
      transmission electron microscopy.
AB  - The egg envelope is an essential structure occurring during oogenesis. It plays
      an important role during the process of fertilization in the large yellow croaker
      Pseudosciaena crocea. Elucidation of egg envelope formation helps us to
      understand fertilization mechanisms in teleosts. In the present work, we studied
      the formation of egg envelope in P. crocea by light microscopy, as well as by
      transmission and scanning electron microscopy. Four layers exist outside the
      oocyte plasmalemma, i.e., theca cell layer, basal membrane, granulosa cell layer
      and zona radiata. According to our observation, zona radiata is a multilaminar
      structure just like the same structure reported in teleosts, but the origin of
      this structure is a little different. Before it is formed, a peripheral space
      filled with different density of vesicles is the place where zona radiata is
      formed. Zona radiata (Z1) is secreted only by oocyte itself, it belongs to the
      primary envelope; zona radiata 2 (Z2) and zona radiata 3 (Z3) belong to the
      secondary envelope, because the two layers are formed after granulosa cells
      appear, and microvilli participate this process. It is very interesting that Z2
      and Z3 are situated between Z1 and the granulosa cell first, but they translocate
      to the other side of Z1. This microanatomy difference may due to the
      participation of microvilli. The new finding about egg envelope formation in P.
      crocea will help us to do further investigation on fertilization mechanisms and
      will make artificial breeding possible which may contribute to the resource
      recovery of this species.

PMID- 22133973
TI  - Low voltage STEM imaging of multi-walled carbon nanotubes.
AB  - We present high magnification STEM images of multi-walled carbon nanotubes
      recorded with a 5 keV electron beam using a Helios Dual Beam microscope and a
      dedicated multi-segment transmission (STEM) detector. Images of carbon nanotubes
      recorded with bright-field (BF), annular dark-field (ADF) and high angle annular
      dark-field (HAADF) signals all show high contrast features, with internal
      structures 1-2 nm in width clearly revealed in the STEM images. Thicker regions
      of the nanotubes appear to show an unusual contrast reversal when comparing ADF
      and HAADF images. An understanding of the image contrast, and its dependence on
      thickness, is obtained by computing simulations of the ADF and HAADF images using
      Monte-Carlo software taking into account electron scattering in the nanotube.

PMID- 22133974
TI  - Assessment of the development and implementation of tools in contract cleaning.
AB  - This paper illustrates and discusses problems with the implementation and use of
      ergonomic tools and techniques in the process of cleaning. Cleaning is an
      occupation with a high risk of developing work-related disorders. One high-strain
      task where recommended tools and techniques are difficult to apply is cleaning
      staircases. This study evaluated the muscular activity of cleaners while mopping
      staircases using two different mop handles and found that an easily adjustable
      mop handle can decrease a cleaner's physical load. The results also show that the
      implementation and contextualization of the mop are of great importance for how a
      mop is used. A more holistic approach is needed to improve the benefits of good
      tools and techniques in cleaning work. More research is needed on how workplace
      organization can be improved to support the implementation of strategies to
      increase the health of professional cleaners.

PMID- 22133975
TI  - Sleep and circadian rhythms in mining operators: limited evidence of adaptation
      to night shifts.
AB  - Cumulative sleep deprivation is often associated with work patterns involving
      night shift or early morning shifts. Adaptation of the circadian system to the
      shift pattern is reported to promote improved duration and quality of sleep and a
      concurrent improvement in performance. The current study followed twenty-nine
      operators at a live-in mining operation working to a seven-day, seven-night shift
      pattern who collected saliva samples for melatonin measurement, recorded sleep
      using activity monitors and diaries, and underwent performance testing
      (psychomotor vigilance task) for one complete roster cycle. The time of onset of
      melatonin secretion changed significantly (P=0.022) across the week of both Day
      and Night shifts (2104 h +/- 16 min versus 2130 h +/- 16 min, respectively), but
      the small magnitude of the change indicates a lack of true circadian rhythm
      adaptation to the lifestyle. Total sleep time was longer following the seventh
      Day shift (associated with a period of 24 h off prior to the commencement of
      Night shifts). There were no other changes in total sleep time. Further, there
      were no improvements in sleep onset latency or sleep efficiency on Day or Night
      shifts. However, reaction times recorded at the end of the shifts slowed across
      the seven Day and seven Night shifts indicative of impairments in psychomotor
      performance (F(6,168)=6.087, P<0.001). The results suggest that previous reports
      of adaptation to consecutive night shifts cannot necessarily be applied to
      onshore or Australian environments. Adaptation is dependent on factors such as
      light exposure, environmental conditions, shift parameters such as wake-up, work
      start and work end times and individual characteristics.

PMID- 22133976
TI  - Towards a capabilities database to inform inclusive design: experimental
      investigation of effective survey-based predictors of human-product interaction.
AB  - A key issue in the field of inclusive design is the ability to provide designers
      with an understanding of people's range of capabilities. Since it is not feasible
      to assess product interactions with a large sample, this paper assesses a range
      of proxy measures of design-relevant capabilities. It describes a study that was
      conducted to identify which measures provide the best prediction of people's
      abilities to use a range of products. A detailed investigation with 100
      respondents aged 50-80 years was undertaken to examine how they manage typical
      household products. Predictor variables included self-report and performance
      measures across a variety of capabilities (vision, hearing, dexterity and
      cognitive function), component activities used in product interactions (e.g.
      using a remote control, touch screen) and psychological characteristics (e.g.
      self-efficacy, confidence with using electronic devices). Results showed, as
      expected, a higher prevalence of visual, hearing, dexterity, cognitive and
      product interaction difficulties in the 65-80 age group. Regression analyses
      showed that, in addition to age, performance measures of vision (acuity, contrast
      sensitivity) and hearing (hearing threshold) and self-report and performance
      measures of component activities are strong predictors of successful product
      interactions. These findings will guide the choice of measures to be used in a
      subsequent national survey of design-relevant capabilities, which will lead to
      the creation of a capability database. This will be converted into a tool for
      designers to understand the implications of their design decisions, so that they
      can design products in a more inclusive way.

PMID- 22133977
TI  - Enhancing credibility of chemical safety studies: no consensus.

PMID- 22133978
TI  - When oxygen runs short: the microenvironment drives host-pathogen interactions.
AB  - Pathogens that colonize or infect the human body have to face varying oxygen
      concentrations within different organs. Inflammation itself promotes oxygen
      consumption within affected tissues and creates a low oxygen environment. As a
      consequence, pathogens and the host immune system have to adapt to rapid changes
      in oxygen availability. Here we summarize recent findings on the adaptation of
      pathogens, host defense mechanisms and treatment strategies against intracellular
      pathogens in a low oxygen environment.

PMID- 22133979
TI  - The association between insight and symptoms in bipolar inpatients: an Italian
      prospective study.
AB  - OBJECTIVE: To evaluate potential differences in insight among bipolar manic,
      mixed and bipolar depressed inpatients and assess the role of clinical and
      demographic characteristics as possible predictors. METHOD: One hundred and
      twenty consecutive inpatients divided into three diagnostic groups were studied
      on admission (T0), at discharge (T1) and at 18weeks after hospitalization (T2).
      The young mania rating scale (YMRS), the Hamilton rating scale for depression
      (HAMD) and the scale to assess unawareness of mental disorder (SUMD) were used.
      RESULTS: Patients with mixed mania showed highest scores on the SUMD than
      patients with mania or bipolar depression. It was found a significant
      relationship between improvements in mania and in the insight. The level of
      insight at baseline was the only predictor of awareness in social consequences,
      moreover clinical and demographic characteristics were predictors of insight into
      mental illness. For what concerns insight about therapy benefits it was
      influenced by level of mania at baseline. CONCLUSION: The three general
      dimensions of insight revealed significant differences among the three groups.
      Regression models suggest that insight is a multidimensional concept in which
      some aspects are state-related, associated with psychopathology, whereas others
      are trait-like qualities, not directly associated with symptoms and predicted
      only by level at baseline.

PMID- 22133980
TI  - Factitious disorder in a psychogeriatric inpatient.

PMID- 22133981
TI  - A case of severe oral self-injurious Tourette's syndrome alleviated by
      pregabalin.
AB  - Self-injurious behavior (SIB) associated with Tourette's syndrome (TS) is a
      severe neuropsychiatric condition that causes significant distress and can impair
      social functioning. The current treatment options for the condition include
      pharmacological, physical and psychosocial interventions. However, given the need
      for more effective interventions, especially for those patients who are
      unresponsive and/or intolerant to standard medications, further exploration of
      novel treatments is imperative. In this report, we present a case of SIB-TS that
      was successfully treated with pregabalin. The patient received 1-year of follow
      up and was noted to have considerable improvement in symptoms. Although rigorous
      controlled studies are required, based on our case study, pregabalin may be a
      potential treatment option in some cases of SIB with TS.

PMID- 22133982
TI  - Which psychotropic medications induce hepatotoxicity?
AB  - OBJECTIVE: Safe prescribing practices to minimize pharmaceutically induced liver
      damage or worsening of preexisting conditions require knowledge about medicines
      with hepatotoxic potential. This paper reviews psychotropic medications and their
      effects on the liver. METHODS: A MEDLINE search was performed utilizing the
      phrase "drug-induced liver injury" with various categories of psychiatric drugs.
      Only articles written in English were utilized. RESULTS: Hepatotoxicity can be
      acute or chronic in nature. Medication discontinuation is necessary in acute
      forms, while close monitoring is required in milder forms of medication-induced
      chronic liver damage. Nefazodone, pemoline and/or tacrine are the highest
      offenders. Carbamazepine and valproate products (e.g., divalproex) can lead to
      this adverse event and should be avoided in patients with liver disease, persons
      with alcohol misuse or those consuming high doses of acetaminophen. CONCLUSION:
      Knowing the risk levels associated with various medicines is important;
      prescribing multiple drugs with hepatotoxic effects should be avoided. One should
      educate patients about early warning signs of liver injury. Always provide
      clinical and laboratory monitoring before and during the use of hepatotoxic
      drugs. Clinical features and laboratory results govern medication prescribing
      with ongoing risk-to-benefit ratio assessment during pharmacotherapy.

PMID- 22133983
TI  - Low-dose escitalopram for 2 days associated with corrected QT interval
      prolongation in a middle-aged woman: a case report and literature review.
AB  - Prolongation of the corrected QT interval (QTc) on the electrocardiography is an
      important clinical condition because it increases the risk of torsade de pointes,
      a medical emergency that can cause sudden cardiac death. QTc prolongation can be
      induced by many drugs, including antipsychotics and tricyclic antidepressants
      (TCAs). Compared with TCAs, use of selective serotonin reuptake inhibitors
      (SSRIs) was less likely to cause severe cardiac adverse effects. Escitalopram,
      one of the SSRIs, has shown significant antidepressant efficacy and well
      tolerability. Here, we present one female patient showing QTc prolongation
      induced by low-dose (5 mg/day) treatment of escitalopram for 2 days. The QTc
      returned to normal soon after discontinuation of escitalopram. Clinicians should
      be cautious about cardiac effects when using a SSRI, even in a low dose.

PMID- 22133984
TI  - Fluoxetine-responsive depression in a Chinese cerebrotendinous xanthomatosis.
AB  - Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive, lipid storage
      disorder which is extremely rare in the Chinese population. It is characterized
      by progressive neurologic dysfunction and enlargement of tendon xanthomas, and is
      often accompanied with neuropsychiatric symptoms. Few reports are available
      regarding depression and antidepressant medication in CTX patients. Here, we
      report a Chinese case of CTX associated with fluoxetine-responsive major
      depression.

PMID- 22133985
TI  - IgG4-related disease of the thyroid glands.
AB  - Recent reports on Hashimoto's thyroiditis (HT) with increased numbers of IgG4
      positive plasma cells suggest that this type of HT may have a close relationship
      to IgG4-related disease (IgG4-RD).  This unique subgroup of HT is termed as IgG4
      thyroiditis and reveals distinct clinical, serological, and sonographic features
      from the non-IgG4 thyroiditis group.  On the basis of immunostaining for IgG4, HT
      was divided into an IgG4 thyroiditis group and a non-IgG4 thyroiditis group. 
      Clinically, IgG4 thyroiditis was associated with younger age group, lower female
      male ratio, higher levels of thyroid autoantibodies, diffuse low echogenicity,
      more rapid progress requiring surgical treatment and more subclinical
      hypothyroidism.  Serum IgG4 concentrations elevated in IgG4 thyroiditis and
      decreased significantly after a thyroidectomy.  Histopathologically, IgG4
      thyroiditis showed a higher grade of stromal fibrosis, lymphoplasmacytic
      infiltration, and follicular cell degeneration than non-IgG4 thyroiditis.  IgG4
      thyroiditis may represent IgG4-RD of thyroid gland, because it shares common
      histopathological characteristics with IgG4-RD in other organs.  The
      identification of IgG4-RD of the thyroid gland opens new insights not only for
      patient's treatment with HT but also for the development of new therapeutic
      approaches for this rapidly progressive destructive subtype of HT.  This article
      mainly focuses on reviewing the unique histopathological, clinical, and
      serological features of IgG4 thyroiditis group of HT.  The etiology and genetic
      changes of HT are also discussed.

PMID- 22133986
TI  - Vascular endothelial growth factor inhibitors (anti-VEGF) in the management of
      diabetic macular oedema: a systematic review.
AB  - BACKGROUND AND RESEARCH QUESTION: The authors address the question of whether
      vascular endothelial growth factor inhibitors (anti-VEGF) lead to better clinical
      outcomes than current treatments in patients with clinically manifest diabetic
      macular oedema (DMO), which is the leading cause of vision loss in the working
      age population in developed countries. METHODS: The authors performed a
      systematic literature search in common databases and compiled the evidence
      according to the GRADE methodology. The authors analysed clinically relevant
      improvement of visual acuity, vision-related quality of life and local or
      systemic adverse events. RESULTS: In a proportion of patients (on average 25%),
      VEGF inhibitors result in better visual acuity (>=15 ETDRS letters or equivalent)
      than in patients treated with laser photocoagulation or sham injection. The
      number of injections required for long-term improvement as well as the general
      long-term efficacy is unknown. The evidence is not sufficient to confirm safety
      of the products in patients with DMO and does not suggest superiority of a single
      product. CONCLUSION: For some patients with DMO, VEGF inhibitors seem to be more
      effective as a short-term treatment option than alternative therapies. The
      evidence is not of sufficient quality to confirm safety. Decisions on financing
      should take into account the high price difference between the products and
      ongoing research.

PMID- 22133987
TI  - Outcomes of deep anterior lamellar keratoplasty following successful and failed
      'big bubble'.
AB  - AIM: The most popular technique for deep anterior lamellar keratoplasty (DALK) is
      the 'big bubble' (BB) technique wherein air is injected in the cornea to create a
      bubble that separates Descemet's membrane (DM) from the stroma. An attempt to
      create a BB often results in the cornea being filled with numerous small bubbles
      without the formation of a BB. Manual dissection is then required to complete the
      procedure. The aim of the study is to compare these two groups, successful BB
      versus failed bubble (FB) dissection to determine whether the clinical outcomes
      were different. METHODS: In this retrospective comparative study, 46 patients out
      of 52 who underwent DALK for various corneal stromal diseases such as
      keratoconus, stromal dystrophy or corneal scarring (caused by different
      conditions) were included in the analysis. BB was achieved in 25 patients and in
      the remaining 21 patients a BB separation of the DM was not possible
      necessitating manual lamellar dissection of stroma to get as close to the DM as
      possible. RESULTS: The authors compared best-corrected visual acuity, contrast
      sensitivity, astigmatism, interface densitometry and Scheimpflug pachymetry in
      the two groups. Postoperative corneal thickness was higher in the 'small bubbles'
      group (mean 628.9 vs 564.1 MUm; p<0.0005), but there was no significant
      difference in best-corrected visual acuity, astigmatism, contrast sensitivity and
      densitometry between the groups. CONCLUSIONS: In DALK, manual lamellar dissection
      is a reasonable alternative when BB separation of the DM is not achieved.

PMID- 22133988
TI  - Global estimates of visual impairment: 2010.
AB  - AIM: From the most recent data the magnitude of visual impairment and its causes
      in 2010 have been estimated, globally and by WHO region. The definitions of
      visual impairment are the current definitions of presenting vision in the
      International Classification of Diseases version 10. METHODS: A systematic review
      was conducted of published and unpublished surveys from 2000 to the present. For
      countries without data on visual impairment, estimates were based on newly
      developed imputation methods that took into account country economic status as
      proxy. RESULTS: Surveys from 39 countries satisfied the inclusion criteria for
      this study. Globally, the number of people of all ages visually impaired is
      estimated to be 285 million, of whom 39 million are blind, with uncertainties of
      10-20%. People 50 years and older represent 65% and 82% of visually impaired and
      blind, respectively. The major causes of visual impairment are uncorrected
      refractive errors (43%) followed by cataract (33%); the first cause of blindness
      is cataract (51%). CONCLUSION: This study indicates that visual impairment in
      2010 is a major health issue that is unequally distributed among the WHO regions;
      the preventable causes are as high as 80% of the total global burden.

PMID- 22133989
TI  - Refractive profile in oculocutaneous albinism and its correlation with final
      visual outcome.
AB  - PURPOSE: To evaluate the prevalence of refractive errors in different subtypes of
      oculocutaneous albinism, and to see if there is any correlation between
      refractive errors and final visual outcome in this population. PATIENTS/METHODS:
      This is a retrospective study of 132 albino patients, ranging in age from 0.5 to
      35 years. They were divided into four subtypes: OCA1A, OCA1B and OCA1C, and OCA2.
      Refractive errors were evaluated objectively by cycloplegic refraction and
      subjectively in cooperative patients. Best corrected visual acuity was assessed
      binocularly. Refractive errors were divided into three groups--hypermetropia,
      myopia and astigmatism--to avoid the use of spherical equivalent. RESULTS:
      Refractive errors were mainly astigmatism and hypermetropia. The OCA1A group
      showed high hypermetropia (>= 5 dioptres) in 43.4% of patients, reaching
      significantly higher levels than in other subgroups (p=0.007). Mean visual acuity
      in logMAR was: OCA1A=0.81, OCA1B=0.64, OCA1C=0.61 and OCA2=0.48. Astigmatism
      averaged 2.1 dioptres (consistently with-the-rule), and it was homogeneously
      distributed between all subgroups (53%). CONCLUSIONS: The poorest visual acuity
      was found in those with OCA1A, which was associated with the highest rate of high
      hypermetropia (statistically significant different from other subgroups).
      Astigmatism was the most common visually significant refractive error across all
      subtypes of albinism. These results may help to clarify the prevalence of
      refractive errors in albino patients and aid the prediction of visual outcome in
      this heterogeneous population.

PMID- 22133990
TI  - Children's morning and evening salivary cortisol: pattern, instruction compliance
      and sampling confounders.
AB  - BACKGROUND/AIMS: Salivary cortisol has been widely used to assess childhood
      stress. Yet, there is no consensus on reference concentrations, awakening
      response, guideline compliance and contribution of sampling factors to the
      variation in children's salivary cortisol levels. METHODS: Samples were collected
      from 444 Belgian children participating in the ChiBS study (5-11 years old) on
      two consecutive weekdays at four moments: awakening, 30 min later, 60 min later
      and in the evening. A checklist requested awakening time, collection hours and
      guideline compliance. RESULTS: Reference values were determined. Mixed model
      analyses revealed that age, time compliance and awakening time contributed
      significantly to the variance in cortisol levels. In only 52.5% of the children a
      cortisol morning increase was observed. Participants with no morning increase
      showed higher awakening but lower post-awakening concentrations on that day, and
      the morning response showed a small negative correlation with the time lag
      between first and second sampling. CONCLUSION: This study emphasizes the
      importance of excluding extreme time deviation and correcting for age and
      awakening time. Appearance of a cortisol morning increase was only found in
      approximately half of the children, suggesting the absence of the cortisol
      awakening response as a general characteristic. Also, this could partially be
      explained by poor time compliance.

PMID- 22133991
TI  - Comparing the effectiveness of error-correction strategies in discrete trial
      training.
AB  - Error-correction strategies are essential considerations for behavior analysts
      implementing discrete trial training with children with autism. The research
      literature, however, is still lacking in the number of studies that compare and
      evaluate error-correction procedures. The purpose of this study was to compare
      two error-correction strategies: Independent Probe and Delay across learners with
      autism in an intensive intervention program. Two studies were conducted. The
      first study compared the two procedures across receptive tasks for 3 individuals,
      and differential effects were seen across learners. The second study compared the
      two procedures across tact trials with two of the same learners and found that
      individual differences were noted, but in addition, the more effective error
      correction strategy was consistent across the two verbal operants (i.e.,
      receptive in Study 1, tacts in Study 2). These combined studies suggest the
      effectiveness of error-correction strategies may be individualized to the learner
      but may generalize across operants.

PMID- 22133992
TI  - A pilot study examining the initial effectiveness of a brief acceptance-based
      behavior therapy for modifying diet and physical activity among cardiac patients.
AB  - Approximately 90% of cardiac events are attributable to a small number of
      modifiable behavioral risk factors that, if changed, can greatly decrease
      morbidity and mortality. However, few at-risk individuals make recommended
      behavioral changes, including those who receive formal interventions designed to
      facilitate healthy behavior. Given evidence for the potential of specific
      psychological factors inherent in acceptance-based behavior therapy (ABBT; that
      is, intolerance of discomfort, mindfulness, and values clarity) to impact health
      behavior change, the authors evaluated the feasibility and initial effectiveness
      of an ABBT pilot program designed to increase adherence to behavioral
      recommendations among cardiac patients. Participants (N = 16) were enrolled in
      four, 90-min group sessions focused on developing mindfulness and distress
      tolerance skills, and strengthening commitment to health-related behavior change.
      Participants reported high treatment satisfaction and comprehension and made
      positive changes in diet and physical activity. This was the first evaluation of
      an ABBT program aimed at increasing heart-healthy behaviors among cardiac
      patients.

PMID- 22133993
TI  - An evaluation of the effects of experimenter control of objects on individuals'
      engagement in object stereotypy.
AB  - In two experiments, the authors evaluated the extent to which (a) individuals
      preferred engaging in object stereotypy versus observing an experimenter while
      the experimenter engaged in object stereotypy and (b) an experimenter's
      engagement in object stereotypy decreased the participants' engagement in object
      stereotypy. Results of Experiment 1 indicated that behaver-controlled (BC) object
      stereotypy was preferred over experimenter-controlled (EC) object stereotypy by
      three of four participants. Results of Experiment 2 indicated that EC object
      stereotypy decreased object stereotypy for only one of three participants.
      Implications of these findings for determining the relative importance of control
      over stimulation generated by stereotypy are briefly discussed.

PMID- 22133994
TI  - [Antihormonal therapy in breast cancer and mTOR inhibitors].
AB  - Hormonal dependence of breast cancer has been known for a long time, yet about
      half of breast cancers with estrogen receptor will not respond to antihormonal
      therapy. Now, we know that this resistance may be related to a dysfunction of the
      estrogen pathway, or that of growth factors and particularly the pathway of cell
      activation PI3K/Akt/mTOR. Prevention of these different mechanisms of resistance
      could involve combination therapies such as anti-estrogens (SERMs, aromatase
      inhibitors) with inhibitors of the activity of growth factors that are
      particularly temsirolimus and everolimus for the activation pathway cell
      PI3K/Akt/mTOR.

PMID- 22133995
TI  - Initial design of a novel suction enteroscope for endoscopic locomotion in the
      small bowel (with video).
AB  - BACKGROUND: The upper GI tract and the colon are readily accessible
      endoscopically, but the small intestine is relatively difficult to evaluate.
      OBJECTIVE: To demonstrate the feasibility of using suction as a means of
      locomotion and to assess the initial design of a suction enteroscope. DESIGN:
      Feasibility study. SETTING: Animal laboratory. INTERVENTION: Various prototype
      suction devices designed in our laboratory were tested in swine small intestine
      in a force test station. For in vivo experiments in live anesthetized animals,
      two suction devices (1 fixed tip and 1 movable tip) were attached to the outside
      of the endoscope. By creating suction in the fixed tip, the endoscope was
      anchored while the movable tip was advanced. Suction was then applied to the
      extended tip to attach it to the distal bowel. Suction on the fixed tip was then
      released and the movable tip with suction pulled back, resulting in advancement
      of the endoscope. These steps were sequentially repeated. Intestinal segments
      were sent for pathologic assessment after testing. RESULTS: Force generated
      ranged from 0.278 to 4.74 N with 64.3 to 88 kPa vacuum pressure. A linear
      relationship was seen between the pull force and vacuum pressures and tip surface
      area. During in vivo experiments, the endoscope was advanced in 25-cm segmental
      increments with sequential suction-and-release maneuvers. No significant bowel
      trauma was seen on pathology and necropsy. LIMITATION: The enteroscopy system
      requires further refinement. CONCLUSION: A novel suction enteroscope was designed
      and tested. Suction tip characteristics played a critical role impacting the
      functionality of this enteroscopy system.

PMID- 22133996
TI  - Randomized, phase II study comparing interferon combined with hepatic arterial
      infusion of fluorouracil plus cisplatin and fluorouracil alone in patients with
      advanced hepatocellular carcinoma.
AB  - OBJECTIVE: This randomized phase II trial compared the response rates to
      treatment with interferon (IFN) combined with hepatic arterial infusion of
      fluorouracil (FU) plus cisplatin (CDDP) or FU alone in patients with advanced
      hepatocellular carcinoma (HCC). METHODS: A total of 114 patients with measurable
      advanced HCC were enrolled and randomized into 2 groups. FU (300 mg/m(2), days 1
      5, days 8-12) with or without CDDP (20 mg/m(2), days 1 and 8) was administered
      via the hepatic artery. IFNalpha-2b was administered 3 times per week for 4
      weeks. RESULTS: The response rates were 45.6% for the IFN/FU + CDDP group and
      24.6% for the IFN/FU group. The response rate was significantly higher in the
      IFN/FU + CDDP group (p = 0.030). The median overall survival period was 17.6
      months in the IFN/FU + CDDP group versus 10.5 months in the IFN/FU group (p =
      0.522). The median progression-free survival period was 6.5 months in the IFN/FU
      + CDDP group versus 3.3 months in the IFN/FU group (p = 0.0048). Hematological
      toxicity was common, but no toxicity-related deaths were observed. CONCLUSION:
      These results show the clinical efficacy of adding CDDP to the hepatic arterial
      infusion of FU in combined chemotherapy regimens with IFN.

PMID- 22133997
TI  - Modelling of auditory evoked potentials of human sleep-wake states.
AB  - The shape of evoked potentials is influenced by the level of vigilance, varying
      with sleep-wake states. In this paper the shape of auditory evoked potentials is
      modelled by taking two factors, both modulating the underlying neuronal
      substrate, into account: 'sensory gating' and 'neuronal firing mode'. Under low
      levels of vigilance sensory gating reduces the amount of neuronal activity
      reaching the cortical centres. Due to a rise in hyperpolarisations of
      thalamocortical neurons associated with an increasing depth of sleep, stimulus
      evoked primary and secondary excitations, seen as correlates of the N1 and N2
      waves of the evoked potential, become smaller. Heightened hyperpolarisations also
      change the spontaneous activity of neurons from the 'tonic' firing mode of
      wakefulness into the 'burst-pause' firing mode of sleep. The large P220 complex
      together with the N350 and N550 waves in sleep are caused by the stimulus induced
      triggering of pauses and bursting of neurons. The results of this modelling
      experiment confirm the view that sleep-specific components such as P220, N350 and
      N550 are waves that facilitate and protect sleep, whereas the wake-specific
      components N1, P2-P3 and N2 have perceptual-cognitive functions. In particular
      the wake P2-P3 wave is sensitive to cognitive functions, such as attention. Based
      on the modelling results it is suggested that component negativities, expressed
      in N1, N2 and N350, reflect excitatory processes, whereas positivity in P2-P3 and
      P220 is a correlate of inhibitory processes. Hence, the large P3 in an attended
      condition is also interpreted as an inhibitory process suppressing irrelevant
      information, facilitation the saliency of relevant information.

PMID- 22133998
TI  - Genetic contributions to acute autonomic stress responsiveness in children.
AB  - Identification of genetic factors that influence stress reactivity is important
      in order to link environmental demands, particularly adversity to disease
      outcome. There is ample literature on genetic contribution to the endocrine
      stress response, while evidence for genetic contribution to individual
      differences in autonomic nervous system function is sparse and produced
      conflicting results. Here, we investigated the influence of two polymorphisms in
      the Catechol-o-methyltransferase (COMT) and serotonin transporter (5-HTT; SCL6A4)
      gene. We examined the autonomic stress response to the Trier Social Stress Test
      for Children in 115 children. Salivary alpha-amylase (sAA) was obtained prior to
      the stressor and repeatedly during recovery as a marker of autonomic reactivity.
      Furthermore, heart rate (HR) and heart rate variability (HRV) were monitored
      continuously. We found differences in ANS stress response associated with each
      polymorphism (all p<.05). Children with the L variant of 5-HTTLPR showed a higher
      increase and sharper recovery of sAA in response to stress than those with S
      variants. For HR, we found differences associated with COMT, i.e. children
      carrying at least one met allele showed lower mean HR increase and slower HR
      recovery in response to the stressor compared to those with two val alleles
      (p<.001) as well as a significant decrease in heart rate variability (p<.05). Our
      findings indicate that these two polymorphisms do indeed influence the ANS
      response to stress. This study provides further evidence for the crucial role of
      genetic factors in the modulation of differences in the acute stress response
      during childhood.

PMID- 22133999
TI  - Etiology, risk factors and sex differences in ischemic stroke in the Ludwigshafen
      Stroke Study, a population-based stroke registry.
AB  - BACKGROUND: Stroke etiology in ischemic stroke guides preventive measures and
      etiological stroke subgroups may show considerable differences between both
      sexes. In a population-based stroke registry we analyzed etiological subgroups of
      ischemic stroke and calculated sex-specific incidence and mortality rates.
      METHODS: The Ludwigshafen Stroke Study is a prospective ongoing population-based
      stroke registry. Multiple overlapping methods of case ascertainment were used to
      identify all patients with incident stroke or transient ischemic attack. Modified
      TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria were applied for
      subgroup analysis in ischemic stroke. RESULTS: Out of 626 patients with first
      ever ischemic stroke in 2006 and 2007, women (n = 327) were older (73.5 +/- 12.6
      years) than men (n = 299; 69.7 +/- 11.5 years; p < 0.001). The age-adjusted
      incidence rate of ischemic stroke was significantly higher in men (1.37; 95% CI
      1.20-1.56) than in women (1.12; 95% CI 0.97-1.29; p = 0.04). Cardioembolism (n =
      219; 35.0%), small-artery occlusion (n = 164; 26.2%), large-artery
      atherosclerosis (n = 98; 15.7%) and 'probable atherothrombotic stroke' (n = 84;
      13.4%) were common subgroups of ischemic stroke. Stroke due to large-artery
      atherosclerosis (p = 0.025), current smoking (p = 0.008), history of smoking (p <
      0.001), coronary artery disease (p = 0.0015) and peripheral artery disease (p =
      0.024) was significantly more common in men than in women. Overall, 1-year
      survival was not different between both sexes; however, a significant age-sex
      interaction with higher mortality in elderly women (>85 years) was detected.
      CONCLUSIONS: Cardioembolism is the main source for ischemic stroke in our
      population. Etiology of ischemic stroke differs between sexes, with large-artery
      atherosclerotic stroke and associated diseases (coronary artery disease and
      peripheral artery disease) being more common in men.

PMID- 22134000
TI  - Neurobehavioural deficits correlate with the cerebral infarction volume of stroke
      animals: a comparative study on ischaemia-reperfusion and photothrombosis models.
AB  - The study investigated the correlation between infarction areas and behavioural
      deficits in middle cerebral artery occlusion (MCAO) and photothrombosis stroke
      models. In the MCAO model, a 0.38 mm-diameter silicone-coated thread was
      introduced through the left external carotid artery and advanced 18 mm via the
      internal carotid artery to the origin of middle cerebral artery of male Sprague
      Dawley rats weighing 300-350 g. The thread was removed for reperfusion after
      occlusion for 0.5, 1 or 2h. In the photothrombosis model, after a midline
      incision on the scalp, a focused light (10,000 lux, 6 mm-diameter) was delivered
      1mm anterior to the bregma and 3mm left of the midline for 5, 10 or 20 min.
      During the first 2 min of irradiation, Rose Bengal dye (30 mg/kg) was injected
      intravenously. Twenty four hours post-surgery, the animals were subjected to
      neurological scoring and behavioural performances, and were sacrificed for
      macroscopic and microscopic examinations of brain injury. Total infarction
      volumes in the MCAO model rats increased in an occlusion time-dependent manner,
      while the infarction volumes in photothrombosis model rats plateaued relatively
      quickly with no time-dependent increase. The MCAO model displayed neurological
      scores and behavioural deficits that correlated well with infarction volumes,
      while relatively poor correlation between infarction volume and neurobehavioural
      abnormalities was evident in the photothrombosis model. The results indicate the
      suitability of the MCAO model for studies on preventive or therapeutic compounds
      related to functional recovery, although the photothrombosis model might be
      useful to generate focused lesions leading to the location-related behavioural
      changes.

PMID- 22134001
TI  - The supplementation of zinc increased the apoptosis of airway smooth muscle cells
      by increasing p38 phosphorylation.
AB  - Proliferation of airway smooth muscle cells (ASMCs) is believed to play an
      important role in causing airway hyperresponsiveness (AHR). It has also been
      reported that platelet-derived growth factor (PDGF) can stimulate proliferation
      of ASMCs. We hypothesize that the concentration of zinc in the bodies of
      asthmatic patients may play a role in PDGF activity and therefore may be related
      to the variations in severity of airway inflammation and narrowing seen in
      asthmatic patients. We investigated the effects and mechanisms of zinc
      supplementation in PDGF-treated ASMCs. In this study, PDGF-treated primary ASMCs
      were cultured with 3, 12, 24, or 96 MUM ZnSO4. We found that the highest
      concentration of ZnSO4 (96 MUM) was cytotoxic for ASMCs. PDGF was used to induce
      ASMCs proliferation under different zinc concentrations. Neither 3 MUM nor 12 MUM
      ZnSO4 inhibited proliferation of PDGF-treated ASMCs, although 24 MUM ZnSO4 caused
      treatment-induced apoptosis in PDGF-treated ASMCs. Supplementation with 24 MUM
      ZnSO4 may therefore increase p38 activation and reduce Akt phosphorylation. Zinc
      supplementation may reduce proliferation of PDGF-treated ASMCs through the
      activation of p38 mitogen-activated protein kinase (MAP kinase) and suppression
      of Akt phosphorylation, which both drive the induction of cellular apoptosis,
      subsequently reducing the proliferation of ASMCs.

PMID- 22134002
TI  - Physical activity monitoring by use of accelerometer-based body-worn sensors in
      older adults: a systematic literature review of current knowledge and
      applications.
AB  - OBJECTIVES: To systematically review the literature on physical activity
      variables derived from body-worn sensors during long term monitoring in healthy
      and in-care older adults. METHODS: Using pre-designed inclusion and exclusion
      criteria, a PubMed search strategy was designed to trace relevant reports of
      studies. Last search date was March 8, 2011. STUDY SELECTION: Studies that
      included persons with mean or median age of >65 years, used accelerometer-based
      body-worn sensors with a monitoring length of >24h, and reported values on
      physical activity in the samples assessed. RESULTS: 1403 abstracts were revealed
      and 134 full-text papers included in the final review. A variety of variables
      derived from activity counts or recognition of performed activities were reported
      in healthy older adults as well as in in-care older adults. Three variables were
      possible to compare across studies, level of Energy Expenditure in kcal per day
      and activity recognition in terms of total time in walking and total activity.
      However, physical activity measured by these variables demonstrated large
      variation between studies and did not distinguish activity between healthy and in
      care samples. CONCLUSION: There is a rich variety in methods used for data
      collection and analysis as well as in reported variables. Different aspects of
      physical activity can be described, but the variety makes it challenging to
      compare across studies. There is an urgent need for developing consensus on
      activity monitoring protocols and which variables to report.

PMID- 22134003
TI  - Ethosuximide reduces allodynia and hyperalgesia and potentiates morphine effects
      in the chronic constriction injury model of neuropathic pain.
AB  - Neuropathic pain is caused by a lesion or disease of the somatosensory nervous
      system and treatment of neuropathic pain remains a challenge. The purpose of the
      present study was to examine the effect of ethosuximide, an anti-epileptic and
      relatively selective T-type calcium blocker and morphine, a prototypical opioid
      in the behavioral responses following the chronic constriction injury (CCI) model
      of neuropathic pain. Experiments were performed on eight groups (n=8) of male
      Sprague-Dawley rats (230-280 g). The animals were injected with saline,
      ethosuximide (100, 200, 300 mg/kg), morphine (4 mg/kg), and a combination of
      morphine (4 mg/kg) plus ethosuximide (100mg/kg, i.p.). The cold-and mechano
      allodynia and thermal hyperalgesia were measured prior to surgery (the day 0) and
      3, 5, 7, 14 and 21 days post surgery. Ethosuximide and morphine significantly
      decreased cold and mechano allodynia and thermal hyperalgesia. However, the co
      administration of both drugs seems to be more effective than the ethosuximide or
      morphine alone on cold and mechano allodynia and thermal hyperalgesia .Our
      results suggest that ethosuximide block tactile and thermal hypersensitivity
      after the CCI model, also, ethosuximide potentiates the analgesic effects of
      morphine in neuropathic pain conditions and behavioral responses.

PMID- 22134004
TI  - Roles of phosphoinositide-dependent kinase-1 in alpha1B-adrenoceptor
      phosphorylation and desensitization.
AB  - The role of phosphoinositide-dependent protein kinase-1 (PDK-1) activity on
      alpha(1B)-adrenoceptor phosphorylation and function was explored using
      pharmacological inhibitors and expression of a dominant-negative mutant of this
      enzyme. Noradrenaline-, phorbol myristate acetate-, lysophosphatidic acid- and
      epidermal growth factor-mediated alpha(1B)-adrenoceptor phosphorylation were
      markedly reduced by the two inhibitors used: UCN-01 [(7-hydroxystaurosporine;
      (3R*,8S*, 9R*, 10R*,12R*)-2,3,9,10,11,12-hexahydro-3-hydroxy-9-methoxy-8-methyl
      10-(methylamino)-8,12-epoxy-1H, 8H-2,7b,12a-triazadibenzo[a,g]
      cyclonona[cde]triden-1-one)] and OSU-03012 [(2-amino-N-[4-[5-(2-phenanthrenyl)-3
      trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-acetamide)]. A similar effect was
      observed in cells expressing a PDK-1 dominant-negative mutant. Phosphorylated PDK
      1 (S241) and protein kinase C alpha (T497) were associated with cell membranes in
      the basal state which increased in response to the hormonal stimuli mentioned
      previously. UCN-01 essentially abolished phospho-PDK-1 membrane-association and
      markedly attenuated that of protein kinase C alpha. Consistent with the findings,
      UCN-01 reduced lysophosphatidic acid- and epidermal growth factor-induced
      alpha(1B-)adrenoceptor desensitization. Our data suggest that PDK-1 plays a
      permissive role in alpha(1B)-adrenoceptor desensitization and phosphorylation and
      participates in the formation of signaling complexes, which delicately modulate
      receptor function and regulation.

PMID- 22134005
TI  - Molecular effects of chemotherapeutic drugs and their modulation by antioxidants
      in the testis.
AB  - Cisplatin-based chemotherapy regimens are preferred in the treatment of a variety
      of cancers. The present study investigated early cumulative molecular effects of
      therapeutic dose-levels of bleomycin, etoposide and cisplatin (BEP) in the testis
      and their modulation by an antioxidant cocktail (AO). Adult male Sprague-Dawley
      rats (N=7/group [G]) were treated with BEP as follows: G1 - control; G2 - AO
      (alpha-tocopherol [100 mg/kg], l-ascorbic acid [50 mg/kg], Zn [40 mg/l] and Se
      [100 MUg/l]); G3 - B, 1.5 mg/kg on day 2; E, 15 mg/kg and P, 3 mg/kg for 4 days,
      and G4 - similar to G3 but also treated with AO for 4 days. In G3, the testis
      weight, sperm count and motility, and activities of enzymatic antioxidants
      decreased and lipid peroxidation increased compared to that in G1 (P<0.05).
      Seminiferous epithelial sloughing and degeneration were observed. In G3, mRNA
      levels of p53, Bcl-2 and Bax were unaltered but protein expression of p53 and Bax
      was up-regulated and that of Bcl-2 was down-regulated (P<0.05). These changes led
      to an increase in terminal deoxynucleotidyl transferase-mediated nick-end
      labeling (TUNEL) positive germ cells indicating cell death (P<0.05). The AO
      recovered the BEP-induced molecular alterations to control levels. The mechanism
      of BEP-induced early testicular damage involves the initiation of oxidative
      stress, up-regulation of pro-apoptotic proteins and induction of cell death.
      Further, the induced testicular structural changes are negligible and less than
      those observed in single drug exposure studies reported in literature. The AO
      significantly ameliorates the BEP-induced pathogenesis of testicular damage
      suggesting its potential therapeutic uses.

PMID- 22134006
TI  - Peripheral antinociception induced by delta-opioid receptors activation, but not
      MU- or kappa-, is mediated by Ca2+-activated Cl- channels.
AB  - Studies have demonstrated that the L-arginine/NO/cGMP pathway and the potassium
      and calcium channels are involved in the mechanisms underlying opioid receptor
      activation. As additional pathways may participate in the observed
      antinociceptive effects following opioid exposure, the aim of our study was to
      determine whether Ca(2+)-activated Cl(-) channels (CaCCs) are involved in
      peripheral antinociception induced by MU-, delta- and kappa-opioid receptor
      activation. Hyperalgesia was induced by intraplantar injection of prostaglandin
      E(2) (PGE(2), 2 MUg). Nociceptive thresholds to pressure (grams) were measured
      using an algesimetric apparatus 3h following injection. The MU-opioid receptor
      agonist morphine (200 MUg), delta-opioid receptor agonist (+)-4-[(alphaR)-alpha
      ((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N
      diethylbenzamide (SNC80, 80 MUg), kappa-opioid receptor agonist bremazocine (50
      MUg), CaCCs blocker niflumic acid (8-64 MUg), CaCCs blocker 5-Nitro-2-(3
      phenylpropylamino) benzoic acid (NPPB, 32-128 MUg), nitric oxide donor sodium
      nitroprusside (SNP, 500 MUg) and cGMP exogenous analogs dibutyryl cGMP (db-cGMP,
      100 MUg) were also administered into the paw. The CaCCs blocker niflumic acid and
      NPPB partially reversed the peripheral antinociception induced by exposure to the
      SNC80 in a dose-dependent manner. In contrast, niflumic acid did not modify the
      antinociceptive effect observed following exposure to morphine or bremazocine.
      Additionally, the peripheral antinociception induced by the NO donor SNP or by db
      cGMP was not inhibited by niflumic acid. These results provide evidence for the
      involvement of CaCCs in the peripheral antinociception induced by SNC80. CaCCs
      activation does not appear to be involved when MU- and kappa-opioid receptors are
      activated. In addition, we did not observe a link between CaCCs and the L
      arginine/NO/GMPc pathway.

PMID- 22134007
TI  - Current therapies in ischemic stroke. Part A. Recent developments in acute stroke
      treatment and in stroke prevention.
AB  - Stroke is the third leading cause of death with an increasing prevalence. In
      previous years many important achievements and new therapeutic strategies have
      been established. This article provides an overview on recent developments and is
      an update to the article of Green et al. that was published in 2004. As this
      article is a comprehensive review we divided it in two parts. In this Part A of
      our review, recent developments in acute stroke treatment and in stroke
      prevention are described. In Part B we will reflect on neuroprotection.

PMID- 22134008
TI  - Juvenile social subjugation induces a sex-specific pattern of anxiety and
      depression-like behaviors in adult rats.
AB  - Child abuse is the most significant environmental risk factor for the development
      of mood disorders, which occur twice as frequently in women as in men. To
      determine whether juvenile social subjugation (JSS) of rats induces mood disorder
      like symptoms, we exposed 28 day-old male and female rats to daily aggressive
      acts from aggressive male residents. Each rat received pins, kicks, and dominance
      postures from the resident for 10 min per day for 10 days. When the rats were
      adults, we tested their anxiety- and depression-like behaviors. In addition, we
      measured circulating basal and stress-evoked corticosterone (CORT) levels, and
      weighed the adrenal glands. Although the amount of JSS was indistinguishable
      between males and females, females were nonetheless more severely affected by the
      experience. Subjugated females became immobile more quickly during forced swim
      tests, and made fewer investigatory approaches during the social interaction test
      than control females. Juvenile social subjugation increased closed arm time in
      the elevated plus maze of males and females, but the effect of social subjugation
      was greater in females. Finally, stress-evoked CORT levels were significantly
      higher, and adrenal gland weights were significantly heavier, in subjugated
      females relative to their controls and to subjugated males. Our results
      demonstrate that JSS increases depression- and anxiety-like behaviors and
      sensitizes the stress response system in a sex-specific manner.

PMID- 22134010
TI  - Gabapentin: a novel drug as add-on therapy in cases of refractory overactive
      bladder in children.
AB  - OBJECTIVE: To determine the effectiveness of gabapentin as an add-on therapy in
      children presenting with overactive bladder (OAB) not responding to conventional
      anticholinergics. MATERIALS AND METHODS: Children with refractory OAB were
      included prospectively from March 2009 to February 2010. The inclusion criterion
      was persistence of symptoms while on conventional anticholinergics for 6 months.
      Gabapentin was prescribed as an add-on therapy. The patients were followed 4
      weekly with bladder diary and urodynamic study was repeated at 3 months. RESULTS:
      There were 31 children, 26 of neurogenic OAB and 5 of non-neurogenic origin. Mean
      +/- SD age was 8.5 +/- 5.3 years. Data were analyzed in 30 patients as treatment
      was terminated in 1 due to adverse effects. Continence improved in 16 (53.3%)
      patients. Voiding volume improved from 175 +/- 90 to 320 +/- 110 ml (p<0.03).
      Objective assessment of OAB symptom relief showed marked improvement (p<0.05).
      Mean maximum cystometric bladder capacity improved from 210 +/- 94 to 360 +/- 110
      ml (p<0.02). The maximal detrusor contraction decreased from 75 +/- 35 to 25 +/-
      15 cmH(2)O (p<0.02). Fourteen patients (46.7%) failed to respond to gabapentin
      therapy. These patients had baseline maximum cystometric bladder capacity <60%
      for age and maximum detrusor contractions >50 cm of water (p<0.03). CONCLUSIONS:
      Gabapentin gives moderate results in children with OAB refractory to conventional
      anticholinergics. In general, the drug is well tolerated with fewer adverse
      effects.

PMID- 22134011
TI  - A preliminary sketch of horn cancer transcriptome in Indian zebu cattle.
AB  - Horn cancer, a type of squamous cell carcinoma, in zebu cattle is an expensive
      affair in Indian agriculture sector, which accounts for 83.34% of total tumors
      found. In general, cancer tissue confirms considerably different expression
      patterns when compared to a normal stage. This includes not only up/down
      regulation, but also, the aberrant gene expression, the presence of different non
      coding RNAs (ncRNAs), pseudogenes expression and genes involved in unusual
      pathways. We employed Roche 454 next generation sequencing platform to sequence
      Bos indicus cancerous and normal horn tissue transcripts. This resulted into a
      total of 909,345 high-confidence deep sequencing reads and detected a range of
      unusual transcriptional events including tumor associated genes. We also
      validated expression of two of the four tested genes in five other similar tissue
      samples by RT-qPCR. Further, seven cancer specific non-coding transcripts were
      accessed and a few of them have been suggested as cancer specific markers. This
      study for the first time provides primary transcriptome sketch of Bos indicus
      horn cancer tissue, and also demonstrates the suitability of the 454 sequencer
      for transcriptome analysis, which supports the concept of varied gene expression
      in cancerous condition.

PMID- 22134009
TI  - Risk-based prostate cancer screening.
AB  - CONTEXT: Widespread mass screening of prostate cancer (PCa) is not recommended
      because the balance between benefits and harms is still not well established. The
      achieved mortality reduction comes with considerable harm such as unnecessary
      biopsies, overdiagnoses, and overtreatment. Therefore, patient stratification
      with regard to PCa risk and aggressiveness is necessary to identify those men who
      are at risk and may actually benefit from early detection. OBJECTIVE: This review
      critically examines the current evidence regarding risk-based PCa screening.
      EVIDENCE ACQUISITION: A search of the literature was performed using the Medline
      database. Further studies were selected based on manual searches of reference
      lists and review articles. EVIDENCE SYNTHESIS: Prostate-specific antigen (PSA)
      has been shown to be the single most significant predictive factor for
      identifying men at increased risk of developing PCa. Especially in men with no
      additional risk factors, PSA alone provides an appropriate marker up to 30 yr
      into the future. After assessment of an early PSA test, the screening frequency
      may be determined based on individualized risk. A limited list of additional
      factors such as age, comorbidity, prostate volume, family history, ethnicity, and
      previous biopsy status have been identified to modify risk and are important for
      consideration in routine practice. In men with a known PSA, risk calculators may
      hold the promise of identifying those who are at increased risk of having PCa and
      are therefore candidates for biopsy. CONCLUSIONS: PSA testing may serve as the
      foundation for a more risk-based assessment. However, the decision to undergo
      early PSA testing should be a shared one between the patient and his physician
      based on information balancing its advantages and disadvantages.

PMID- 22134012
TI  - Testing of the World Health Organization recommended formulations in their
      application as hygienic hand rubs and proposals for increased efficacy.
AB  - BACKGROUND: In Central Europe, alcohol-based hand rubs have been the preferred
      choice for hand hygiene, whereas, in other countries, other preparations have
      been used that are based on other active agents. Recently, a move towards alcohol
      based hand rubs has begun, but they may be costly and unaffordable to some.
      Therefore, the World Health Organization (WHO) has recommended 2 hand rub
      formulations (WHO I and WHO II) for local production in health care settings
      where commercial products are not available or are too expensive. OBJECTIVES: WHO
      I, based on ethanol 80% (vol/vol), and WHO II, based on isopropanol 75%
      (vol/vol), were investigated for their bactericidal efficacy in their application
      as hygienic hand rubs. METHODS: The investigation took place at the Institute for
      Hygiene and Applied Immunology, Medical University Vienna, Austria, as a
      prospective, randomized, in vivo laboratory study, comparative in crossover
      design. Both formulations were tested according to the European Standard EN 1500
      in 2 applications (1 * 3 mL/30 seconds or 2 * 3 mL/2 * 30 seconds). Additionally,
      modifications with increased alcohol concentrations (weight instead of volume
      percent) were tested in the short application. Bactericidal efficacies were
      compared with those of the respective reference procedure "R," ie, rubbing 2 * 3
      mL 60% vol/vol isopropanol for 2 * 30 seconds onto hands artificially
      contaminated with Escherichia coli K12. RESULTS: The short application of either
      WHO formulation resulted in bacterial reductions significantly inferior to the
      respective ones of R. However, prolonging the contact time to 60 seconds or
      increasing the alcohol content produced reductions similar to those of R.
      CONCLUSION: Both WHO-recommended formulations meet the efficacy requirements of
      EN 1500 within 60 seconds but not within 30 seconds. Increasing the respective
      alcohol concentrations from 80% vol/vol to 80% wt/wt and 75% vol/vol to 75% wt/wt
      renders the formulations sufficiently active to conform to the norm also within
      30 sections.

PMID- 22134013
TI  - Minimally invasive urogynecology.
AB  - Laparoscopic and other forms of minimally invasive pelvic floor defect repair
      represent alternative approaches to performing established procedures;
      laparoscopy can offer benefits to the surgeon (improved visualization, access for
      multiple procedures) and patient (decreased pain, scar formation, recuperation,
      and improved cosmesis). Many practitioners prefer the term "minimal access
      surgery" to the more prevalent "minimally invasive surgery," as, ideally, only
      the route of access, not the procedure itself, is changed. Similarly, dialogue
      and debate about the merits and concerns of trocar-based mesh prolapse repair
      kits continue. While gynecology will benefit from further investigations of
      outcomes of minimally invasive pelvic reconstruction,there is evidence already
      that these techniques are feasible and offer options and advantages in the
      treatment of patients with pelvic floor disorders.

PMID- 22134014
TI  - Total and supracervical hysterectomy.
AB  - Despite a long history of success with laparoscopic approach to hysterectomy, the
      majority of hysterectomies in the United States are currently performed via
      laparotomy.48-51 Barriers to the integration of laparoscopic hysterectomy include
      technological difficulties, inadequate training, low levels of peer support,
      potential for decreased reimbursement and misconceptions about laparoscopic
      safety, cost, and technical feasibility.52-54 With the continual evolution of
      minimally invasive hysterectomy techniques, now including robotic, single-port,
      and natural-orifice surgery, it is vital to critically evaluate the literature in
      an effort to offer patients the most safe and effective treatments. This report
      aims to summarize the available data surrounding both the total and supracervical
      laparoscopic hysterectomy and to provide concrete suggestions for maximizing
      success with these procedures.

PMID- 22134015
TI  - Laparoscopic management of adnexal masses.
AB  - With the continued expansion of endoscopic techniques and instruments,
      laparoscopy and minimally invasive techniques are quickly emerging as a feasible
      alternative to laparotomy in managing adnexal masses and ovarian
      cancer.Laparoscopy has the potential to completely and successfully treat both
      benign and malignant adnexal pathology while decreasing unnecessary morbidity
      among patients. Further advances in technology, techniques, and instruments can
      only increase this potential.

PMID- 22134016
TI  - Surgical treatment of endometriosis.
AB  - In this review, the pitfalls that still exist with the surgical treatment of
      endometriosisassociatedpelvic pain have been discussed and the best evidence
      regarding various aspects of surgical techniques have been reviewed. When
      laparoscopy is performed to evaluate a woman with pelvic pain symptoms, it is
      important she be counseled that the primary function of the surgery is to confirm
      the presence (and allow surgical treatment) of endometriosis, and that it is not
      the penultimate diagnostic modality for her pelvic pain. There are many
      etiologies of pelvic pain that present with symptoms resembling those of
      endometriosis-associated pelvic pain that are not diagnosable with laparoscopy,
      such as interstitial cystitis and irritable bowel syndrome. It is unfortunate
      that many women are left with the belief that if a laparoscopy fails to provide a
      diagnosis of a pain generator, then it means there are no diagnoses other than
      that the "pain is in her head," often disparagingly termed "supratentorial"
      byclinicians. In fact, the pain-related diagnoses that are amenable to and
      possibly require a laparoscopy are quite limited, a group of diagnoses that this
      author terms the "dirty dozen" because there are just 12, and only the first 4
      have good evidence to clearly associate them with chronic pelvic pain:1.
      Endometriosis 2. Ovarian remnant syndrome 3. Pelvic inflammatory disease 4.
      Tuberculous salpingitis 5. Adhesions 6. Benign cystic mesothelioma 7.
      Postoperative peritoneal cysts 8. Adnexal cysts (nonendometriotic)9. Chronic
      ectopic pregnancy 10. Endosalpingiosis 11. Residual accessory ovary 12. Hernias:
      ventral, inguinal, femoral, spigelian.I would argue that diagnostic laparoscopy
      in modern gynecology has a limited, if any role, and that when laparoscopy is
      planned for women with chronic pelvic pain, it should be with a very high
      suspicion of a diagnosis and with plans to treat the disease operatively. In this
      era, a negative diagnostic laparoscopy should be a rare event.

PMID- 22134017
TI  - Electrosurgery: principles and practice to reduce risk and maximize efficacy.
AB  - Science becomes art and art becomes function when fundamental principles are
      utilized to dictate surgical practice. Most important, the risk for inadvertent
      thermal injury during electrosurgery can be minimized by a sound comprehension of
      the predictable behaviors of electricity in living tissue.Guided by the
      Hippocratic charge of primum non nocere, the ultimate aim of energy-assisted
      surgery is the attainment of anatomic dissection and hemostasis with the least
      amount of collateral damage and subsequent scar tissue formation.Ideally, the
      surgeon's final view of the operative field should accurately approximate the
      topography discoverable after postoperative healing. Despite the continued
      innovation of products borne to reduce thermal damage and then marketed as being
      comparatively safer, it is the hands and mind of the surgeon that serve to
      preserve tissue integrity by reducing the burden of delayed thermal necrosis and
      taking steps to prevent excessive devitalization of tissue. Regardless of the
      chosen modality, the inseparable and exponentially linked elements of time and
      the quantity of delivered energy must be integrated while purposefully moderating
      to attain the desired tissue effect. Ultimately, the reduction of unwanted
      thermal injury is inherently linked to good surgical judgment and technique, a
      sound comprehension of the applied energy modality, and the surgeon's ability to
      recognize anatomic structures within the field of surgical dissection as well as
      those within the zone of significant thermal change.During the use of any energy
      based device for hemostasis, out of sight must never mean out of mind. If the
      bowel, bladder, or ureter is in close proximity to a bleeder,they should be
      sufficiently mobilized before applying energy. Thermal energy should always be
      withheld until an orderly sequence of anatomic triage is carried out.Whenever a
      vital structure cannot be adequately mobilized, hemorrhage is preferentially
      controlled by using mechanical tamponade or suture ligature.

PMID- 22134018
TI  - Uterine leiomyomas, current concepts: pathogenesis, impact on reproductive
      health, and medical, procedural, and surgical management.
AB  - Leiomyomas are such common tumors of the uterus that at least two-thirds of women
      will have at least one by the age of 50. Despite this high incidence, we know
      relatively little about their cause, growth and development, and contribution to
      the genesis of reproductive disorders. The prevalence of lesions puts women with
      associated butun related symptoms at risk for unnecessary and/or unsuccessful
      interventions,especially if they have not been carefully evaluated and counseled.
      Indeed, because the majority of leiomyomas do not cause symptoms, when a woman
      presents with AUB, infertility, pelvic pain, or vague abdominal complaints, it is
      possible if not likely that the cause of the problem exists elsewhere. The other
      overwhelming impression that can be gleaned is this: when leiomyomas are the
      cause of the symptoms,particularly in women desiring to preserve fertility, the
      tumors have already and frequently induced irreparable harm, a circumstance that
      cries out for a strategy of early detection and interventions designed to
      minimize morbidity.Fortunately, because of the efforts of a few, we are just
      beginning to understand the potential molecular mechanisms by which leiomyomas
      may contribute to reproductive tract symptoms such as AUB, infertility, and
      pregnancy loss, work that may contribute to the development of more specific
      medical therapeutic techniques and strategies. The use of increasingly precise
      and accessible imaging for diagnosis,combined with the application of customized
      intrauterine drug-releasing systems or minimally invasive and highly accurate
      targeted ablative technologies that minimize collateral damage, may provide women
      the opportunity to avoid the mutilating,painful, expensive, and frequently
      unsuccessful surgical interventions of today that are applied to end-stage
      disease.For the present, clinicians should evaluate any woman with reproductive
      tract symptoms and leiomyomas carefully and with skepticism, ensuring that they
      have done all that is necessary to determine if the lesion or lesions are related
      to the problem. If leiomyomas are the suspected or known cause, clinicians must
      also be prepared to offer or otherwise provide access to the complete spectrum of
      care that the patient deserves, regardless of the limitations of the clinician's
      training, experience,or institutional environment. Such an approach will limit
      the number of unnecessary and ineffective interventions and, it is hoped,
      minimize morbidity while optimizing quality of life for affected women.

PMID- 22134019
TI  - Simulation and education in gynecologic surgery.

PMID- 22134020
TI  - Laparoendoscopic single-site surgery in gynecology.

PMID- 22134021
TI  - Laparoscopy in pregnancy and the pediatric patient.
AB  - Minimally invasive surgery is now standard of care for many procedures in
      pediatric gynecology. Laparoscopy has been well documented to produce faster
      recovery,decreased postoperative pain, and because of smaller incisions, a better
      cosmetic result. These are important when considering an active pediatric
      patient. Although a laparoscopic approach to endometriosis, adnexal masses, and
      ovarian torsion are well supported in the literature in the pediatric patient,
      more data are needed with regard to SILS in younger patients. Laparoscopy seems
      to be a better approach to oopheropexy in children undergoing radiation, and in
      resection of certain mullerian anomalies; however, the numbers are low.Similarly
      in pregnant patients, laparoscopy provides for shorter recovery times,decrease
      analgesic use and shorter hospital stays. Concerns about poor fetal outcomes in
      surgery during pregnancy for non gynecologic problems have been brought to light;
      however, the evidence indicates that these outcomes can be attributed to the
      nature of the underlying disease and not the surgical approach. With regard to
      pneumoperitoneum the effect of CO2 insufflation on fetal physiology and long-term
      outcomes remains unclear, and will continue to be an issue of controversy until
      larger studies are published.With both the pediatric and pregnant populations,
      laparoscopic complications can be diminished when performed by skilled surgeons
      with strict adherence to good technical principles. The advantages of laparoscopy
      are great, and this approach should be considered in pediatric and pregnant
      patients.

PMID- 22134022
TI  - The core of a competent surgeon: a working knowledge of surgical anatomy and safe
      dissection techniques.
AB  - The competent gynecologic surgeon has a sure, working knowledge of the anatomy in
      the field of pelvic dissection and is expert in the techniques and in the
      millimeter by millimeter progression of surgical dissections. When operating in
      the pelvis, the surgeon always asks several questions. The first is, "In what
      anatomic area am I dissecting?" This question defines the anatomy to be dissected
      out. The second is,"What dissection techniques will I use here?" The measured
      steps of surgical dissection give the surgeon the confidence to proceed with the
      operation, while safeguarding the integrity of the surrounding anatomic
      structures. With less blood loss and less trauma to the tissues and anatomic
      structures, the surgeon may expect a better surgical outcome for the patient.

PMID- 22134023
TI  - Advances in the knowledge and technical skills in laparoscopy and minimally
      invasive surgery support the need for a special issue dedicated to this subject
      in Obstetrics and Gynecology Clinics of North America.

PMID- 22134024
TI  - Long-term measurements of unattached radon progeny concentrations using solid
      state nuclear track detectors.
AB  - We described a method for long-term passive measurements of unattached fraction
      fp of the potential alpha energy concentration of radon progeny from a set of
      measured (f1, f2, f3) values, where fi=Ci/C0 (i=1, 2, 3), and C0, C1, C2 and C3
      were the concentrations of 222Rn, and the airborne concentrations of 218Po, 214Pb
      and 214Bi, respectively. Jacobi room model parameters were randomly sampled from
      their lognormal distributions to search for (f1', f2', f3') sufficiently close to
      (f1, f2, f3) and to determine fp. There was 99% and 88% chance obtaining an
      estimated fp value within 50% and 30% of the true value, respectively.

PMID- 22134025
TI  - Comparison of the TL fading characteristics of Ge-doped optical fibres and LiF
      dosimeters.
AB  - Fading is important in choosing appropriate thermoluminescence (TL) materials for
      particular applications. Comparison is made herein of changes due to fading in
      the TL yield of Ge-doped fibres and lithium fluoride (LiF) dosimeters, for
      varying temperature and dose. The fading is independent of dose for all
      investigated dosimeters while the loss in TL yield reduces for lower storage
      temperatures. At room temperature and for 133 days of storage, a maximum signal
      loss of 5% has been observed for both forms of LiF dosimeter, while 9 and 50 MUm
      core diameter Ge-doped fibres produced a loss of 11% and 8%, respectively.

PMID- 22134026
TI  - Reconstruction of the isotope activity content of heterogeneous nuclear waste
      drums.
AB  - Radioactive waste must be characterized in order to verify its conformance with
      national regulations for intermediate storage or its disposal. Segmented gamma
      scanning (SGS) is a most widely applied non-destructive analytical technique for
      the characterization of radioactive waste drums. The isotope specific activity
      content is generally calculated assuming a homogeneous matrix and activity
      distribution for each measured drum segment. However, real radioactive waste
      drums exhibit non-uniform isotope and density distributions most affecting the
      reliability and accuracy of activities reconstruction in SGS. The presence of
      internal shielding structures in the waste drum contributes generally to a strong
      underestimation of the activity and this in particular for radioactive sources
      emitting low energy gamma-rays independently of their spatial distribution. In
      this work we present an improved method to quantify the activity of spatially
      concentrated gamma-emitting isotopes (point sources or hot spots) in
      heterogeneous waste drums with internal shielding structures. The isotope
      activity is reconstructed by numerical simulations and fits of the angular
      dependent count rate distribution recorded during the drum rotation in SGS using
      an analytical expression derived from a geometric model. First results of the
      improved method and enhancements of this method are shown and are compared to
      each other as well as to the conventional method which assumes a homogeneous
      matrix and activity distribution. It is shown that the new model improves the
      accuracy and the reliability of the activity reconstruction in SGS and that the
      presented algorithm is suitable with respect to the framework requirement of
      industrial application.

PMID- 22134027
TI  - Heavy metal sensitivity and bioconcentration in oribatid mites (Acari, Oribatida)
      Gradient study in meadow ecosystems.
AB  - In this study we aimed to identify different reactions of oribatid species to
      heavy metal pollution and to measure concentrations of cadmium, zinc and copper
      in oribatid species sampled along a gradient. Oribatid mites were sampled
      seasonally during two years in five meadows located at different distances from
      the zinc smelter in the Olkusz District, southern Poland. Oribatids were shown to
      withstand critical metal concentration and established comparatively abundant and
      diverse communities. The highest abundance and species richness of oribatids were
      recorded in soils with moderate concentrations of heavy metals. Four different
      responses of oribatid species to heavy metal pollution were recognized. Heavy
      metals (Zn, Pb, Cd, Ni) and various physical (bulk density, field capacity, total
      porosity) and chemical (K(av), P(av), N, C, pH) factors were recognized as the
      structuring forces that influence the distribution of oribatid species. Analysis
      by atomic absorption spectrophotometry revealed large differences in metal body
      burdens among species. None of the species can be categorized as accumulators or
      non-accumulators of the heavy metals - the pattern depends on the metal. The
      process of bioconcentration of the toxic metal (regulated) and essential elements
      (accumulated) was generally different in the five oribatid species studied.

PMID- 22134028
TI  - Diffusive gradients in thin films (DGT) for the prediction of bioavailability of
      heavy metals in contaminated soils to earthworm (Eisenia foetida) and oral
      bioavailable concentrations.
AB  - The applicability of diffusive gradients in thin-films (DGT) as a biomimic
      surrogate was investigated to determine the bioavailable heavy metal
      concentrations to earthworm (Eisenia foetida). The relationships between the
      amount of DGT and earthworm uptake; DGT uptake and the bioavailable
      concentrations of heavy metals in soils were evaluated. The one-compartment model
      for the dynamic uptake of heavy metals in the soil fitted well to both the
      earthworm (R(2)=0.641-0.990) and DGT (R(2)=0.473-0.998) uptake data. DGT uptake
      was linearly correlated with the total heavy metal concentrations in the soil
      (aqua regia), the bioavailable heavy metal concentrations estimated by fractions
      I+II of the standard measurements and testing (SM&T) and physiologically based
      extraction test (PBET, stomach+intestine). The coefficients of determination
      (R(2)) of DGT uptake vs. aqua regia were 0.433, 0.929 and 0.723; vs. SM&T
      fractions (I+II) were 0.901, 0.882 and 0.713 and vs. PBET (stomach+intestine)
      were 0.913, 0.850 and 0.649 for Pb, Zn and Cu, respectively. These results imply
      that DGT can be used as a biomimic surrogate for the earthworm uptake of heavy
      metals in contaminated soils as well as predict bioavailable concentrations of
      heavy metals estimated by SM&T (I+II) and PBET as a human oral bioavailable
      concentrations of heavy metals.

PMID- 22134029
TI  - Intron 4 polymorphism of the endothelial nitric oxide synthase (eNOS) gene is
      associated with decreased NO production in a mercury-exposed population.
AB  - Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a
      potent vasodilator and plays a prominent role in regulating the cardiovascular
      system. Decreased basal NO release may predispose to cardiovascular diseases.
      Evidence suggests that the 27 nt repeat polymorphism of the intron 4 in the eNOS
      gene may regulate eNOS expression. On the other hand, some recent reports
      strongly suggest an association between methylmercury (MeHg) exposures and
      altered NO synthesis. In the present study, we investigate the contribution of
      the 27-pb tandem repeat polymorphism on nitric oxide production, which could
      enhance susceptibility to cardiovascular disease in the MeHg-exposed study
      population. Two-hundred-two participants (98 men and 104 women), all chronically
      exposed to MeHg through fish consumption were examined. Mean blood Hg
      concentration and nitrite plasma concentration were 50.5 +/- 35.4 MUg/L and 251.4
      +/- 106.3n M, respectively. Mean systolic and diastolic blood pressure were 120.1
      +/- 19.4mm Hg and 72.0 +/- 10.6mm Hg, respectively. Mean body mass index was 24.5
      +/- 4.3 kg/m(2) and the mean heart rate was 69.8 +/- 11.8 bpm. There were no
      significant differences in age, arterial blood pressure, body mass index or
      cardiac frequency between genotype groups (all P>0.05). However, we observed
      different nitrite concentrations in the genotypes groups, with lower nitrite
      levels for the 4a4a genotype carriers. Age, gender and the presence of intron 4
      polymorphism contributed to nitrite reduction as a result of blood Hg
      concentration. Taken together, our results show that the 27 nt repeat
      polymorphism of the intron 4 in the eNOS gene increases susceptibility to
      cardiovascular diseases after MeHg exposure by modulating nitric oxide levels.

PMID- 22134030
TI  - Occupational safety and health practices among flower greenhouses workers from
      Alto Tiete region (Brazil).
AB  - In this preliminary study the occupational safety and health practices among
      flower greenhouses workers were evaluated. The study was carried out in the alto
      Tiete region, located at the Sao Paulo State, Brazil. Inadequate welfare
      facilities; poor pesticide storage, use and disposal conditions; use of highly
      toxic pesticides; lack of adequate data regarding pesticide use; and incorrect
      use and maintenance of PPE were observed in most of the visited greenhouses.
      These results suggest that, in greenhouses, workers may be at higher risk of
      pesticide exposure, due to many factors that can intensify the exposure such as
      the lack of control on reentry intervals after pesticide application. Specific
      regulations are needed to ensure better OSH practices on pesticide use and to
      improve working conditions in greenhouses, in order to deal with the
      peculiarities of greenhouse working environment. Some of the special requirements
      for greenhouses workers' protection are the establishment of ventilation criteria
      for restricted entry interval; clear reentry restrictions; and EPI for workers
      other than applicators that need to enter the greenhouse before expiring REI
      interval. Another important way to improve OSH practices among workers includes
      the distribution of simple guidelines on the dos and don'ts regarding OSH
      practices in greenhouses and extensively training interventions to change the
      perception of hazards and the behavior towards risk.

PMID- 22134031
TI  - Characterization of polycyclic aromatic hydrocarbon emissions in the particulate
      phase from burning incenses with various atomic hydrogen/carbon ratios.
AB  - Polycyclic aromatic hydrocarbons in the particulate phase generated from burning
      various incense was investigated by a gas chromatography/mass spectrometry. Among
      the used incenses, the atomic H/C ratio ranged from 0.51 to 1.69, yielding the
      emission factor ranges for total particulate mass and PAHs of 4.19-82.16 mg/g and
      1.20-9.50 MUg/g, respectively. The atomic H/C ratio of the incense was the key
      factor affecting particulate mass and the PAHs emission factors. Both the maximum
      emission factor and the slowest burning rate appear at the H/C ratio of 1.57. The
      concentrations of the four-ring PAHs predominated and the major species among the
      16 PAHs were fluoranthene, phenanthrene, pyrene, and chrysene for most incense
      types. The benzo[a]pyrene, benzo[a]anthracene, benzo[b]fluoranthene, and
      dibenzo[a,h]anthracene accounted for 87.08-93.47% of the total toxic equivalency
      emission factor.

PMID- 22134032
TI  - Okadaic acid inhibits cell growth and photosynthetic electron transport in the
      alga Dunaliella tertiolecta.
AB  - Okadaic acid (OA), which is produced by several dinoflagellate species, is a
      phycotoxin known to induce a decrease of biomass production in phytoplankton.
      However, the mechanisms of OA cytotoxicity are still unknown in microalgae. In
      this study, we exposed the green microalga Dunaliella tertiolecta to OA
      concentrations of 0.05 to 0.5 MUM in order to evaluate its effects on cell
      division, reactive oxygen species production and photosynthetic electron
      transport. After 72 h of treatment under continuous illumination, OA
      concentrations higher than 0.10 MUM decreased culture cell density, induced
      oxidative stress and inhibited photosystem II electron transport capacity. OA
      effect in D. tertiolecta was strongly light dependent since no oxidative stress
      was observed when D. tertiolecta was exposed to OA in the dark. In the absence of
      light, the effect of OA on culture cell density and photosystem II activity was
      also significantly reduced. Therefore, light appears to have a significant role
      in the toxicity of OA in microalgae. Our results indicate that the site of OA
      interaction on photosynthetic electron transport is likely to be at the level of
      the plastoquinone pool, which can lead to photo-oxidative stress when light
      absorbed by the light-harvesting complex of photosystem II cannot be dissipated
      via photochemical pathways. These findings allowed for a better understanding of
      the mechanisms of OA toxicity in microalgae.

PMID- 22134033
TI  - Influence of urban activities on polycyclic aromatic hydrocarbons in
      precipitation: distribution, sources and depositional flux in a developing
      metropolis, Fortaleza, Brazil.
AB  - We measured polycyclic aromatic hydrocarbons (PAHs) in bulk precipitation in the
      Fortaleza metropolitan area, Ceara, Brazil, for the first time. Because little
      information is available concerning PAHs in tropical climatic regions, we
      assessed their spatial distribution and possible sources and the influence of
      urban activities on the depositional fluxes of PAHs in bulk precipitation. The
      concentrations of individual and total PAHs (Sigma(PAHs)) in bulk precipitation
      ranged from undetectable to 133.9 ng.L(-1) and from 202.6 to 674.8 ng.L(-1),
      respectively. The plume of highest concentrations was most intense in a zone with
      heavy automobile traffic and favorable topography for the concentration of
      emitted pollutants. The depositional fluxes of PAHs in bulk precipitation
      calculated in this study (undetectable to 0.87 MUg.m(-2).month(-1)) are 4 to 27
      times smaller than those reported from tourist sites and industrial and urban
      areas in the Northern Hemisphere. Diagnostic ratio analyses of PAH samples showed
      that the major source of emissions is gasoline exhaust, with a small percentage
      originating from diesel fuel. Contributions from coal and wood combustion were
      also found. Major economic activities appear to contribute to pollutant
      emissions.

PMID- 22134034
TI  - A review of studies on atmospheric mercury in China.
AB  - Due to the fast developing economy, mercury (Hg) emissions to the atmosphere from
      Chinese mainland have increased rapidly in recent years. Consequently, this issue
      has received a considerable attention internationally. This paper reviews the
      current understanding of and knowledge on atmospheric Hg emissions, distribution
      and transport in China. The magnitude of Hg emissions to the atmosphere from
      Chinese anthropogenic sources has been estimated to be in the range of 500-700
      tons per year, whereby comprising a significant proportion of the globe total
      anthropogenic emissions. Emissions of Hg from natural surfaces including bare
      soil, water, and vegetation covered soil tend in a comparison to be higher in
      China than in Europe and North America, indicating the importance of this source
      category. Atmospheric Hg exhibits a significant concentration variability among
      urban, semi-remote, and remote areas. Total Gaseous Mercury (TGM) concentrations
      in urban areas of China were often 1.5 - 5 folds higher compared to the
      corresponding settings in North America and Europe. In turn, particulate mercury
      (PHg) concentrations in urban areas of China were up to two orders of magnitude
      higher compared to North America and Europe. Atmospheric observations made at
      strictly remote sites in China also include the presence of occasional high
      concentrations of TGM, and the more short-lived fractions PHg and Reactive
      Gaseous Mercury (RGM). Accordingly, Hg deposition fluxes tended to be higher in
      China, with remote areas and urban areas being 1-2 times and 1-2 magnitude higher
      than those in North America and Europe, respectively.

PMID- 22134035
TI  - Natural attenuation of arsenic in soils near a highly contaminated historical
      mine waste dump.
AB  - Arsenic-contaminated soils near historical As-rich mine waste in Jachymov (Czech
      Rep.), resulting from the smelting and seepage of the mine waste pore water, were
      studied to examine As partitioning between solid phases and pore waters.
      Mineralogical and geochemical analyses showed that As is exclusively associated
      with unidentified amorphous Fe oxyhydroxides, poorly crystalline goethite and
      hematite as adsorbed and coprecipitated species (with up to 3.2 wt.% As).
      Adsorption of As by Fe oxyhydroxides is likely to be a major control on the
      migration of As in the soil pore water containing only up to 15 MUg L(-1) As(V).
      The slight variations in the dissolved As(V) concentrations do not follow the
      total contents of As in the soil or adsorbed As, but appeared to be a function of
      pH-dependent sorption onto Fe oxyhydroxides. The geochemical modelling using
      PHREEQC-2 supported the efficiency of As(V) adsorption by Fe oxyhydroxides in the
      soil affected by As-rich waste solution seepage. It also suggested that active Fe
      oxyhydroxides has a strong attenuation capacity in soil that could effectively
      trap the aqueous As(V) from the unremitting waste seepage for the next approx.
      11600 years.

PMID- 22134036
TI  - Conrad and Becker's "10 Criteria" fall short of addressing conflicts of interest
      in chemical safety studies.

PMID- 22134037
TI  - Extraction, purification and characterization of the plant-produced HPV16 subunit
      vaccine candidate E7 GGG.
AB  - Several studies indicated that biopharmaceuticals based on the recombinant
      protein E7 of human papillomavirus (HPV) can serve as therapeutic vaccines
      preventing the development of cancer in women infected with high-risk types of
      HPV such as HPV16. Here, we report effective extraction and purification of a
      plant-produced E7GGG-lichenase fusion protein, an HPV16 subunit vaccine
      candidate, from Nicotiana benthamiana plants, to a high yield. The target
      contains the modified HPV16 E7 protein internally fused to the surface loop of a
      truncated, hexa-His- and KDEL-tagged variant of bacterial lichenase, and has been
      previously shown to possess anti-cancer activity in an animal model. We purified
      the protein using a combination of immobilized metal-ion affinity chromatography
      and gel filtration. The achieved purity of the final product was 99% as confirmed
      by Coomassie or SYPRO Ruby staining after sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and by analytical size exclusion chromatography coupled with
      multi-angle laser light scattering. The overall yield was 50% corresponding to
      0.1g of protein per 1 kg plant biomass. Only slight changes in these parameters
      were observed during the process scale-up from 50 g to 1 kg of processed leaf
      biomass.

PMID- 22134038
TI  - In vivo monitoring of cerebral agmatine by microdialysis and capillary
      electrophoresis.
AB  - Agmatine is a putative neurotransmitter in the brain. Current analytical
      techniques do not allow the detection of agmatine in extracellular fluid, making
      it difficult to study its physiological role. However, a new method for in vivo
      monitoring agmatine in the brain was developed. Capillary zone electrophoresis
      and laser induced fluorescence detection (CZE-LIFD) was used to measure nanomolar
      concentrations of agmatine in submicroliter sample volumes. This analytical
      technique proved to detect 0.49 attomole of agmatine improving the sensitivity of
      previous analytical techniques. On the other hand, the hippocampus is a brain
      region well known for having a population of agmatine containing neurons.
      Therefore, intracerebral microdialysis was performed in the hippocampus and
      agmatine was extracted from the extracellular environment. Detectable amounts of
      agmatine were found in dialysates from probes located in the hippocampus but not
      from the probes located in the lateral ventricle. Furthermore, extracellular
      agmatine was calcium and impulse dependent and depolarization of hippocampal
      neurons increased extracellular agmatine concentration. The methods reported here
      are sensitive enough to study the physiological role of brain agmatine in freely
      moving animals.

PMID- 22134039
TI  - A monolith purification process for virus-like particles from yeast homogenate.
AB  - Monoliths are an alternative stationary phase format to conventional particle
      based media for large biomolecules. Conventional resins suffer from limited
      capacities and flow rates when used for viruses, virus-like particles (VLP) and
      other nanoplex materials. The monolith structure provides a more open pore
      structure to improve accessibility for these materials and better mass transport
      from convective flow and reduced pressure drops. To examine the performance of
      this format for bioprocessing we selected the challenging capture of a VLP from
      clarified yeast homogenate. Using a recombinant Saccharomyces cerevisiae host it
      was found hydrophobic interaction based separation using a hydroxyl derivatised
      monolith had the best performance. The monolith was then compared to a known
      beaded resin method, where the dynamic binding capacity was shown to be three
      fold superior for the monolith with equivalent 90% recovery of the VLP. To
      understand the impact of the crude feed material confocal microscopy was used to
      visualise lipid contaminants, deriving from the homogenised yeast. It was seen
      that the lipid formed a layer on top of the column, even after regeneration of
      the column with isopropanol, resulting in increasing pressure drops with the
      number of operational cycles. Removal of the lipid pre-column significantly
      reduces the amount and rate of this fouling process. Using Amberlite/XAD-4 beads
      around 70% of the lipid was removed, with a loss of VLP around 20%. Applying a
      reduced lipid feed versus an untreated feed further increased the dynamic binding
      capacity of the monolith from 0.11 mg/mL column to 0.25 mg/mL column.

PMID- 22134040
TI  - Phase II study of bolus 5-fluorouracil and leucovorin combined with weekly
      paclitaxel as first-line therapy for advanced gastric cancer.
AB  - OBJECTIVE: We evaluated the efficacy and safety of bolus 5-fluorouracil (5-FU)
      and leucovorin combined with weekly paclitaxel (FLTAX) in advanced gastric cancer
      (GC) patients. METHODS: Patients with untreated stage IV GC received paclitaxel
      80 mg/m(2) as a 1-hour infusion, followed by 5-FU 600 mg/m(2) as a bolus infusion
      and L-leucovorin 250 mg/m(2) as a 2-hour infusion on days 1, 8 and 15. Treatment
      cycles were repeated every 28 days. The primary endpoint was response rate.
      RESULTS: Thirty-five patients were enrolled. The median age was 62 years (range
      34-75). Twenty-one patients (60%) had diffuse-type cancer and 11 had peritoneal
      metastasis. The confirmed response rate was 43% (95% CI 26-61) with 15 partial
      responses. Stable disease was observed in 16 (46%) patients. Median progression
      free survival and overall survival were 6.8 months (95% CI 5.8-7.4) and 16.2
      months (95% CI 10.0-22.8), respectively. Grade 3-4 adverse events were:
      neutropenia (54%), febrile neutropenia (3%), diarrhea (6%) and sensory neuropathy
      (11%). CONCLUSION: FLTAX showed a desirable safety profile, and the efficacy
      against advanced GC was encouraging. FLTAX may be a good option for GC patients
      with deteriorated general condition, and a randomized clinical trial in such
      patients is currently underway.

PMID- 22134041
TI  - Fronto-limbic volumetric changes in major depressive disorder.
AB  - BACKGROUND: Fronto-limbic dysregulation in major depressive disorder (MDD) may be
      influenced by early life stress and antidepressant treatment. The present
      structural MRI study aimed to determine the relationship between amygdala,
      cingulate and subgenual prefrontal cortex volumes in MDD and their associations
      with child abuse and antidepressants. METHODS: Right-handed subjects (21-50
      years), meeting DSM-IV criteria for MDD, either with (n=19) or without (n=20)
      childhood sexual or physical abuse. Healthy controls (n=34) were matched for age,
      sex, education and smoking. 3D-MPRAGE images with a spatial resolution of 1.5
      mm*1.0 mm*1.0 mm were acquired with a Siemens Sonata 1.5 T system. Volumes of
      subgenual prefrontal cortex, amygdala and affective, cognitive, superior and
      posterior divisions of cingulate cortex were analyzed using DISPLAY software
      using reliable volumetric protocols. Groups were compared using ANCOVA, with
      intracranial volume as a covariate. RESULTS: MDD subjects had low cingulate
      (cognitive division) and high amygdala volumes. Low cingulate volume was related
      to abuse and treatment history. Amygdala volume was predicted by subgenual
      prefrontal and cingulate (cognitive division) volumes and the presence of
      paracingulate cortex. LIMITATIONS: This study was cross sectional and the sample
      size was limited for subgroup and correlational analyses. SUMMARY: Our data
      suggest that MDD may be associated with alterations in anterior cingulate cortex
      and amygdala. Morphological variation, early stress and stress-protective factors
      may contribute to differences in fronto-limbic structures in MDD.

PMID- 22134042
TI  - Predictors of response among patients with panic disorder treated with
      medications in a naturalistic follow-up: the role of adult separation anxiety.
AB  - BACKGROUND: Efficacy of treatments for panic disorder is well established, but
      not all patients respond. Adult separation anxiety has been found to predict
      poorer response to CBT, but its effect on response to medication has not been
      previously explored. STUDY AIM: The aim of this study is to investigate if panic
      agoraphobic spectrum factors, including 'separation anxiety' factor predict
      treatment outcome in patients with panic disorder. STUDY SAMPLE: Participants who
      met criteria for PD (n=57) completed baseline assessment and 12 months follow-up.
      Patients were administered the Panic Agoraphobic Spectrum Self-Report (PAS-SR,
      Lifetime and Last-Month Versions), and the Panic Disorder Severity Scale (PDSS).
      We examined patients who met the following criteria at baseline: 1) PDSS total
      score>7; 2) no current Axis I comorbidity with major depression; 3) no lifetime
      or current bipolar disorder. All patients were treated with evidence-based
      psychopharmacological treatment for panic disorder during the 12-month
      observation period. RESULTS: Twenty eight patients (48.1%) achieved remission
      during the follow-up period. In a logistic regression model, controlling for
      baseline severity, gender and age, only the last-month PAS-SR 'separation
      anxiety' factor was associated with a lower likelihood of remission. CONCLUSIONS:
      Signs and symptoms of separation anxiety in adulthood, as assessed with the PAS
      SR Last Month version, are predictors of poor treatment outcome in patients with
      PD. We submit that the assessment of panic-agoraphobic spectrum features,
      including adult separation anxiety, should become routine of clinical assessment
      of patients with PD. It is likely that a better psychopathological
      characterization of patients may inform treatment selection, and result in better
      treatment outcome.

PMID- 22134043
TI  - Efficacy and safety of olanzapine in the treatment of Japanese patients with
      bipolar I disorder in a current manic or mixed episode: a randomized, double
      blind, placebo- and haloperidol-controlled study.
AB  - BACKGROUND: No current data were available regarding the efficacy and safety of
      olanzapine in Japanese patients with bipolar I disorder with a current
      manic/mixed episode. METHODS: Patients received blindly olanzapine (5-20 mg/day;
      N=105), haloperidol (2.5-10 mg/day; N=20), or placebo (N=99) for 3 weeks. For the
      following 3 weeks, the olanzapine and haloperidol groups continued their
      treatment, while the placebo group switched blindly to olanzapine. The primary
      efficacy measure was the mean change in Young Mania Rating Scale (YMRS) total
      score; secondary efficacy measures included bipolar disorder remission rate and
      switch-to depression. Safety measures included treatment-emergent adverse events
      (TEAEs), weight and extrapyramidal symptoms (EPSs). RESULTS: YMRS total score
      significantly decreased in the olanzapine group compared with the placebo group (
      5.62 [95% CI: -8.87, -2.37], p<0.001) after 3 weeks. Compared with haloperidol,
      olanzapine was not markedly different in improving overall bipolar
      symptomatology, and fewer olanzapine-treated patients switched to symptomatic
      depression (2.4% vs 16.7%, p=0.014). Overall incidences of TEAEs were not
      significantly different among the groups, and EPSs in olanzapine group were less
      severe than in the haloperidol group. LIMITATIONS: The small haloperidol sample
      size limited the conclusions that can be drawn from the statistical comparisons
      between the active treatments. CONCLUSIONS: This was the first study to evaluate
      an atypical antipsychotic in Japanese patients with manic bipolar I disorder.
      Consistent with previous non-Japanese studies, olanzapine was generally well
      tolerated and superior to placebo in improving the severity of manic symptoms.
      Compared to haloperidol, fewer olanzapine-treated patients switched to
      symptomatic depression, and EPSs were less severe.

PMID- 22134044
TI  - Pharmacotherapeutic trends in 2231 psychiatric inpatients with bipolar depression
      from the International AMSP Project between 1994 and 2009.
AB  - BACKGROUND: Pharmacological treatment of bipolar depression is a complex and
      controversial issue, and its real-world practice remains largely unknown. METHOD:
      Observational analysis of the pharmacotherapy of 2231 psychiatric inpatients with
      a current episode of bipolar depression. The study was based on cross-sectional
      prescription data from European psychiatric hospitals that had been repeatedly
      collected between 1994 and 2009 through the collaborative Drug Safety in
      Psychiatry (AMSP) program. RESULTS: Overall 81.3% of patients received
      antidepressants (AD) (7.8% monotherapy), 57.9% antipsychotics (AP), 50.1%
      anticonvulsants (AC), 47.5% tranquilizers, and 34.6% lithium (Li). Use over time
      was stable for AD, decreased for Li, and increased for AC, AP and tranquilizers.
      Pronounced increases were specifically observed for quetiapine, lamotrigine and
      valproate. Use of tricyclic AD decreased but its prevalence was still 11.8% in
      2009. Venlafaxine was used by 19.5% in 2009. We also observed an increase of
      polypharmacy combining AD, AP, AC and Li. From 2006 to 2009 37.0% received
      concomitant treatment with three, and 6.4% even with all four of those drug
      classes. LIMITATIONS: Observational cross-sectional study without follow-up or
      additional clinical information. CONCLUSIONS: Monotherapy with antidepressants
      and any use of tricyclic AD and venlafaxine still has a considerable prevalence
      in bipolar depression, but this is controversial due to the reported risk of
      treatment emergent affective switches. Triple and quadruple therapy is not
      evidence-based but increasingly used in clinical practice. This may reflect an
      attempt to overcome treatment failure, and further studies should evaluate
      efficacy and safety of this common practice.

PMID- 22134045
TI  - Cognitive/affective and somatic/affective symptom dimensions of depression are
      associated with current and future inflammation in heart failure patients.
AB  - BACKGROUND: Little is known about whether cognitive/affective depressive symptoms
      or somatic/affective depressive symptoms are associated with inflammation in
      heart failure (HF), or that the relation is confounded with disease severity.
      AIM: To examine the association between depressive symptom dimensions in HF
      patients with inflammatory markers cross-sectionally and prospectively, while
      adjusting for appropriate confounders. RESULTS: Consecutive HF patients completed
      the Beck Depression Inventory at inclusion and at 12 month follow-up. Cytokines
      were assessed at both occasions. Cross-sectional--multivariate linear regression
      analysis (n=110) demonstrated that cognitive/affective depressive symptoms were
      independently associated with increased levels of sTNFR2 (beta=0.20, p<0.05) and
      IL-1ra (beta=0.28, p<0.01). Somatic/affective depressive symptoms were
      independently related to sTNFR2 (beta=0.21, p<0.05). Prospective--(n=125) the
      level of cognitive/affective depressive symptoms at inclusion was prospectively
      associated with increased levels of sTNFR1 and sTNFR2 (beta=0.21 and 0.25 resp.
      p<0.05), independent of covariates. Change in somatic/affective depressive
      symptoms over the 12 month period was associated with sTNFR2 (beta=0.30,
      p=0.008). At symptom level, core depressive cognitions such as hopelessness and
      guilt drove the relation between the sTNF receptors and the cognitive/affective
      component, while having sleep problems was the most important associate of the
      somatic/affective dimension. CONCLUSIONS: Baseline cognitive/affective depressive
      symptoms were prospectively associated with sTNFR1 and sTNFR2 in HF patients,
      while change in somatic/affective depressive symptoms was associated with sTNFR2,
      independent from clinical and demographic covariates. Further studies are
      warranted to replicate these findings and to examine the association between
      depression dimensions, inflammation and prognosis in HF.

PMID- 22134046
TI  - Efficacy of ustekinumab in nail psoriasis and improvement in nail-associated
      quality of life in a population treated with ustekinumab for cutaneous psoriasis:
      an open prospective unblinded study.
AB  - BACKGROUND: The objective of this open-label prospective unblinded study was to
      evaluate the efficacy of ustekinumab in nail psoriasis and the improvement of
      patient quality of life (QoL). METHODS: Twenty-seven patients with plaque
      psoriasis and fingernail involvement were treated with the standard ustekinumab
      regimen. Outcome measures were assessed at baseline and at weeks 4, 16, 28 and 40
      using the nail psoriasis severity index (NAPSI). QoL was evaluated before and
      after treatment using the international onychomycosis-specific questionnaire.
      RESULTS: The pairwise comparisons showed statistically significant NAPSI
      reduction in 4, 16, 28 and 40 weeks compared to the baseline score. The mean
      NAPSI at week 40 was 2.00 +/- 2.337. The international onychomycosis QoL scores
      were significantly improved at all time points (p < 0.001). No patient reported
      any adverse events. CONCLUSIONS: Even though no control group was used in this
      study, ustekinumab was effective and safe in the treatment of nail psoriasis.

PMID- 22134047
TI  - Measurement of breath acetone concentrations by selected ion flow tube mass
      spectrometry in type 2 diabetes.
AB  - Selected ion flow tube-mass spectrometry (SIFT-MS) can measure volatile compounds
      in breath on-line in real time and has the potential to provide accurate breath
      tests for a number of inflammatory, infectious and metabolic diseases, including
      diabetes. Breath concentrations of acetone in type 2 diabetic subjects
      undertaking a long-term dietary modification programme were studied. Acetone
      concentrations in the breath of 38 subjects with type 2 diabetes were determined
      by SIFT-MS. Anthropomorphic measurements, dietary intake and medication use were
      recorded. Blood was analysed for beta hydroxybutyrate (a ketone body), HbA1c
      (glycated haemoglobin) and glucose using point-of-care capillary (fingerprick)
      testing. All subjects were able to undertake breath manoeuvres suitable for
      analysis. Breath acetone varied between 160 and 862 ppb (median 337 ppb) and was
      significantly higher in men (median 480 ppb versus 296 ppb, p = 0.01). In this
      cross-sectional study, no association was observed between breath acetone and
      either dietary macronutrients or point-of-care capillary blood tests. Breath
      analysis by SIFT-MS offers a rapid, reproducible and easily performed measurement
      of acetone concentration in ambulatory patients with type 2 diabetes. The high
      inter-individual variability in breath acetone concentration may limit its
      usefulness in cross-sectional studies. Breath acetone may nevertheless be useful
      for monitoring metabolic changes in longitudinal metabolic studies, in a variety
      of clinical and research settings.

PMID- 22134048
TI  - [Endometrial cancer imaging].
AB  - Endometrial cancer is staged according to the International Federation of
      Gynecology and Obstetrics surgical system. Clinical estimation of stage, however,
      can be inaccurate in more than 20%, and therefore, preoperative imaging of the
      disease may assist in planning the optimal course of treatment. Magnetic
      resonance imaging (MRI) may detect gross myometrial extension or extension of
      tumor to the cervical stroma, which can alter management and therefore help in
      preoperative surgical planning. This issue is increasingly relevant as less
      invasive surgical techniques, such as laparoscopic surgeries, are becoming more
      commonplace for lower stage cancers. Currently, MRI is the most widely used
      modality for preoperative planning.

PMID- 22134049
TI  - Cordycepin inhibits renal interstitial myofibroblast activation probably by
      inducing hepatocyte growth factor expression.
AB  - Renal interstitial fibrosis is the common end point of progressive renal diseases
      leading to the deterioration and eventual loss of renal function. This study
      investigated the effect and potential mechanism of cordycepin on activation of
      renal interstitial fibroblast cells. The time and dose-responses of cordycepin in
      rat renal interstitial fibroblast (NRK-49F) cells were analyzed. The
      proliferation of NRK-49F and the expression of alpha-smooth muscle actin (alpha
      SMA) and fibronectin (FN) were examined. The expression and translocation of Smad
      proteins also were measured by western blot and indirect immunofluorescence
      staining. The mRNA level of hepatocyte growth factor (HGF) and the expression of
      HGF receptor c-Met and its phosphorylation (p-Met) were also detected. Cordycepin
      suppressed the proliferation of NRK-49F and the expression of alpha-SMA and FN
      induced by transforming growth factor-beta1 (TGF-beta1). The pretreatment of
      cordycepin markedly attenuated the nuclear translocation and accumulation of
      activated Smad2/3 in NRK-49F cells. Furthermore, cordycepin not only increased
      HGF expression, but also induced HGF secretion, as well as HGF receptor
      phosphorylation in NRK-49F cells. Cordycepin possesses renoprotective activity
      through suppression myofibroblast activation. This action is mediated, at least
      in part, by blocking nuclear translocation and accumulation of activated Smad2/3
      protein and up-regulating anti-fibrotic HGF expression and secretion and HGF
      receptor activation.

PMID- 22134050
TI  - Immunohistochemical localization and biochemical changes in catalase and
      superoxide dismutase during metamorphosis in the olfactory system of frog
      Microhyla ornata.
AB  - Amphibian metamorphosis is characterized by rapid tissue remodeling and drastic
      changes in the body structure and function. Like other organs, olfactory system
      also undergoes a dramatic rearrangement as the animal experiences transition from
      aquatic to terrestrial habitat. Reactive oxygen species (ROS) are known to play
      an important role during anuran metamorphosis and role of antioxidant enzymes
      like catalase and superoxide dismutase (SOD) are believed to play a major role in
      these processes. Therefore, we hypothesize that antioxidant enzymes in the
      olfactory system may undergo changes that reflect metamorphic processes.
      Immunohistochemical study revealed the presence of catalase and SOD in the
      olfactory receptor neurons and also granular reaction in olfactory epithelium of
      medial diverticulum during metamorphosis. Catalase and SOD immunoreactivity were
      seen in the epithelium of lateral diverticulum, vomeronasal organ as
      metamorphosis proceeds and in the apical lining of olfactory epithelium of adult
      frog. Biochemical study showed that catalase activity gradually increases in the
      olfactory system from metamorphic stage 40-46 and adult, while SOD activity
      decreases from stage 40 to 46 and increases in adult. Thus, the localization and
      relative levels of catalase and SOD during metamorphosis in the olfactory system
      suggests that these enzymes may be involved in protection from oxidative damage.

PMID- 22134052
TI  - Paediatric moyamoya in mainland France: a comprehensive survey of academic
      neuropaediatric centres.
AB  - BACKGROUND: Epidemiological data of paediatric moyamoya disease/syndrome
      (MMD/MMS) in non-Asian populations are scarce. METHODS: A questionnaire was sent
      to every French neuropaediatric academic centre to estimate the prevalence,
      incidence, familial form rate and location of paediatric MMD/MMS cases. Specific
      paediatric data were also retrieved from the most recent nationwide Japanese
      study. RESULTS: A 100% response rate was obtained. The prevalence of paediatric
      MMD/MMS was estimated at 0.39/100,000 children (95% CI: 0.28-0.49), and the
      incidence was estimated at 0.065/100,000 children/year (95% CI: 0.025-0.12), with
      7.5% familial cases. The prevalence was homogenous within the different
      administrative areas. CONCLUSIONS: This comprehensive survey of MMD/MMS in
      academic neuropaediatric centres suggests that the prevalence of the disease in
      children in France is approximately 1/20th of that estimated in Asia.

PMID- 22134051
TI  - Synaptic activity-induced Ca(2+) signaling in avian cochlear nucleus
      magnocellularis neurons.
AB  - Neurons of the avian cochlear nucleus magnocellularis (NM) receive glutamatergic
      inputs from the spiral ganglion cells via the auditory nerve and feedback
      GABAergic inputs primarily from the superior olivary nucleus. We investigated
      regulation of Ca(2+) signaling in NM neurons with ratiometric Ca(2+) imaging in
      chicken brain slices. Application of exogenous glutamate or GABA increased the
      intracellular Ca(2+) concentration ([Ca(2+)](i)) in NM neurons. Interestingly,
      GABA-induced Ca(2+) responses persisted into neuronal maturation, in both
      standard and energy substrate enriched artificial cerebrospinal fluid. More
      importantly, we found that electrical stimulation applied to the glutamatergic
      and GABAergic afferent fibers innervating the NM was able to elicit transient
      [Ca(2+)](i) increases in NM neurons, and the amplitude of the Ca(2+) responses
      increased with increasing frequency and duration of the electrical stimulation.
      Antagonists for ionotropic glutamate receptors significantly blocked these
      [Ca(2+)](i) increases, whereas blocking GABA(A) receptors did not affect the
      Ca(2+) responses, suggesting that synaptically released glutamate but not GABA
      induced the Ca(2+) signaling in vitro. Furthermore, activation of GABA(A)
      receptors with exogenous agonists inhibited synaptic activity-induced [Ca(2+)](i)
      increases in NM neurons, suggesting a role of GABA(A) receptors in the regulation
      of Ca(2+) homeostasis in the avian cochlear nucleus neurons.

PMID- 22134055
TI  - The relevance of photopheresis to autoreactive diseases.

PMID- 22134054
TI  - Immunohistochemical and functional characterization of nitric oxide signaling
      pathway in isolated aorta from Crotalus durissus terrificus.
AB  - We characterized the nitric oxide (NO)-cyclic GMP-phosphodiesterase-5 (PDE5)
      pathway in Crotalus durissus terrificus aorta. Concentration responses curves to
      acetylcholine (ACh), sodium nitroprusside (SNP), BAY41-2272 (soluble guanylyl
      cyclase [sGC] stimulator), BAY60-2770 (sGC activator) and tadalafil (PDE5
      inhibitor) were constructed in phenylephrine (10 MUM)-precontracted tissues with
      intact (E(+)) or denuded (E(-)) endothelium. ACh (0.0001-10 MUM) and SNP (0.0001
      10 MUM) relaxed aorta, which were reduced by the NO synthase (L-NAME,100 MUM) or
      the sGC inhibitors (ODQ, 10 MUM). Tadalafil (0.0001-10 MUM) relaxed E(+) rings
      with potency (pEC(50)) and maximal response (E(max)) values of 7.34+/-0.02 and
      105+/-8%, respectively. E(-) or ODQ treatment significantly (P<0.05) reduced
      tadalafil relaxations (66+/-18% and 71+/-7%, respectively). BAY41-2272 (0.0001
      300 nM) produced concentration-dependent relaxations in E(+) rings, which were
      reduced by addition of either ODQ or L-NAME (16.0- and 5.2-fold rightward shifts,
      respectively). The relaxation of BAY60-2770 was markedly potentiated by ODQ and L
      NAME (41.0- and 9.7-fold leftward shifts, respectively), whereas in E(-) the
      pEC(50) values were shifted by 7-fold to the right. Immunohistochemistry,
      followed validation by transcriptomic analysis, revealed the presence of eNOS in
      endothelium, whereas nNOS was observed only in perivascular nerves. sGC and PDE5
      were expressed in smooth muscle. Thus, NO-sGC-PDE5 pathway is evolutionarily
      present in Crotalus sp. vessels, and has a remarkable degree of functional
      similarity to mammalian vessels.

PMID- 22134056
TI  - [Systemic learning planification for medical students during oncology clinical
      rotation].
AB  - The expected increase in cancer incidence emphasizes the need for specific
      training in this area, including either family physician or specialized
      oncologists. In France, the fourth to sixth years of medical teaching include
      both theoretical classes at the university and daily actual practice at the
      hospital. Thus, clinical rotations are thought to play a major role in the
      training of medical students and also largely participate to the choice of the
      student of his/her final specialty. Pedagogic quality of these rotations is
      dependent on multiple parameters, including a rigorous planification of the
      expected learning. Here, we reported a systemic planification of learning
      activities for medical students during an oncology rotation at the Paoli
      Calmettes Institute in Marseille, France, a regional comprehensive cancer center.
      This planification includes an evaluation of learning requirements, definition of
      learning objectives, selection of learning methods and choice of methods of
      assessment of the students' achievement of these objectives as well as the
      learning activity itself.

PMID- 22134057
TI  - Effect of a single brushing with two Zn-containing toothpastes on VSC in morning
      breath: a 12 h, randomized, double-blind, cross-over clinical study.
AB  - This randomized, double-blind, 12 h clinical study tested the effect of a single
      brushing with two Zn-containing toothpastes on volatile sulfur compound (VSC)
      levels in morning breath. The following toothpastes were each tested by all 28
      participants: A-Zn toothpaste, B--experimental toothpaste (Zn citrate + PVM/MA
      copolymer) and C--control toothpaste without Zn. The evening prior to test days
      participants brushed their teeth for 2 min with 1 g toothpaste. 12 h later and
      prior to eating or performing oral hygiene, morning breath levels of VSC (H(2)S,
      CH(3)SH) were analysed by gas chromatography. Subjects then rinsed for 30 s with
      5 ml cysteine and breath samples were analysed for H(2)S (H(2)S(cys)). Median VSC
      (area under the curve) values were compared for A, B and C and the effects of A
      and B on VSC were compared with C. Toothpaste B was more effective than both
      toothpastes A and C in reducing H(2)S, CH(3)SH and H(2)S(cys) (p < 0.05).
      Compared with toothpaste C, toothpastes A and B reduced H(2)S by 35% and 68%,
      respectively (p = 0.003), and CH(3)SH by 12% and 47%, respectively (p = 0.002).
      Toothpaste B reduced H(2)S(cys) by 48% compared with toothpaste C (p = 0.001). It
      is suggested that the superior effect of the experimental toothpaste was most
      likely due to a higher Zn concentration combined with longer retention of Zn due
      to the PVM/MA copolymer.

PMID- 22134058
TI  - Imbalance of Th1 and Th2 cells in cardiac injury induced by ambient fine
      particles.
AB  - The study was to explore the potential immunoregulatory mechanisms linking fine
      particles and cardiac injury. Wistar kyoto (WKY) rats were exposed by
      intratracheal instillation to fine particles with the doses of 0.0, 1.6, 8.0 and
      40.0mg/kg b.w., respectively. The exposure was conducted once a day, for three
      consecutive days. Twenty-four hours after the last exposure, the rats were
      sacrificed. Th1- and Th2-related transcription factors and cytokines were
      assessed in left ventricle of rats. The mRNA expressions of Th1- and Th2-related
      transcription factors signal transducer and activator of transcriptionl 1
      (STAT1), signal transducer and activator of transcriptional 6 (STAT6), GATA-3 and
      T-bet were assessed in left ventricle of rats using real-time PCR. Meanwhile, the
      levels of Th1- and Th2-related cytokines IL-4, IL-13 and interferon gamma (IFN
      gamma) were determined by ELISA kits in cardiac homogenate supernatant of rats.
      Furthermore, the protein expression of IL-4 and IFN-gamma were detected in
      myocardium by Western blot. The results of cardiac histology demonstrated
      exacerbated cardiac lesions and histological characterization of inflammation and
      degeneration in rats after exposure to fine particles. Moreover, fine particles
      induced significant increase of IL-4 and IL-13 and decrease of IFN-gamma in
      myocardium of rats. The mRNA expression of STAT1, STAT6 and GATA-3 were up
      regulated in left ventricle of rats in a dose-dependent manner, whereas T-bet was
      significantly down-regulated. The variations of these cytokines demonstrated the
      imbalance of Th1 and Th2 cytokines existed in cardiac injuries induced by fine
      particle. The imbalance of Th1/Th2 cytokines might be one of the mechanisms of
      immunotoxicity of cardiovascular system induced by ambient fine particles.

PMID- 22134059
TI  - Ultrastructural and proteomic alteration of superficial masseter muscle after
      lower jaw sagittal advancement in rat.
AB  - OBJECTIVE: The purpose of this study was to investigate the ultrastructural and
      proteomic alteration of the superficial masseter muscle (SM) after lower jaw
      sagittal advancement in a rat model. METHODS: Six 35-day-old male Sprague-Dawley
      rats were utilized in a transmission electron microscopy study, and six more in a
      proteomic study. The rats were randomly allocated to two experimental and two
      control groups (n=3). The experimental groups were fitted with fixed devices that
      protruded the mandible, whereas the control groups were not fitted with the
      devices. The rats were sacrificed 3 days after mandibular advancement.
      Transmission electron microscopy analysis, Western blot analysis, comparative
      proteomic analysis, and matrix-assisted laser desorption/ionization-time-of
      flight (MALDI-TOF) mass spectrometry (MS) were applied to profile qualitative and
      quantitative differences in the morphology and proteome of rat SM. RESULTS: Under
      the transmission electron microscope, morphological changes of the SM were
      associated with deregulation of the myofibrillar network accompanied by fibre
      rupture, interlaced myofilaments, and changes in the mitochondria and
      sarcoplasmic reticulum cisternae. The shape of mitochondria changed. Proteomic
      analysis identified fourteen differentially expressed proteins involved in
      metabolism, contraction or the cytoskeleton, and transport. Amongst these, the
      expression of 13 proteins increased and 1 decreased. According to Western blot
      analysis, myosin heavy chain II was down-regulated. CONCLUSION: Three days after
      functional mandibular advancement, the ultrastructure of rat SM had changed. This
      change paralleled changes in metabolic, contractile and cytoskeletal, and
      transport proteins, which affected SM physiology. The energy metabolism of SM
      increased, and the muscle velocity and force of contraction decreased.

PMID- 22134060
TI  - Analysis of syndecan-1 gene promoter during mouse tooth development.
AB  - OBJECTIVE: Syndecan-1 plays an important role in cell proliferation in dental
      papilla during tooth development. This study aimed to clarify the transcription
      mechanisms that regulate syndecan-1 gene expression in dental papilla. DESIGN: We
      analysed genomic conservation and putative transcriptional factor binding sites
      of syndecan-1 gene loci using the bioinformatics tool VISTA. To identify the
      region responsible for syndecan-1 gene expression in mouse dental papilla cells
      (MDPCs) in vitro, the 1.5-kb upstream region of the mouse syndecan-1 coding
      region was inserted upstream of the enhanced green fluorescent protein (EGFP) or
      luciferase gene, and promoter activity was examined by transient reporter gene
      expression assay in cultured MDPCs. To examine the binding of the upstream
      binding factor, we performed chromatin immunoprecipitation (ChIP) assay. RESULTS:
      VISTA analysis showed that the 1.5-kb upstream region was highly conserved
      amongst species, and three GC-rich motifs, as well as a TATA-box-like motif, were
      identified in this region. Reporter gene assay showed that the 1.5-kb upstream
      region of mouse syndecan-1 induced reporter gene expression in MDPCs. Deletion of
      the promoter from the 5'-end to 339 bp upstream reduced luciferase activity by
      nearly half vs. the 1.5-kb sequence. Further deletion up to 68 bp resulted in
      further loss of luciferase activity. On ChIP assay, we found direct recruitment
      of Sp3 transcription factor to the GC-rich motif region. CONCLUSION: The 1.5-kb
      upstream region of the syndecan-1 gene was sufficient to induce its expression in
      dental papilla, and binding of Sp3 transcription factor may play a pivotal role
      in this syndecan-1 induction.

PMID- 22134062
TI  - An exploration of young women's experiences of living with excess weight.
AB  - The experiences of eight young women with excess weight were explored using a
      semi structured interview consisting of open ended questions and also the Child
      Attachment Interview (CAI). Interpretative Phenomenological Analysis indicated
      four group themes around participants' experience of having excess weight;
      emotional regulation, focus on family relationships, lack of control and sense of
      self. The CAIs indicated that many of the young women had adopted a caring role
      in their families, which were often characterized by conflict within family
      relationships. Dismissing their own vulnerability and emotional needs in
      preference for self reliance was the dominant attachment strategy adopted by
      participants. It is suggested that obesity is a complex condition and one that
      requires an understanding of each individual's experiences and relationship with
      food, in order to offer treatment that is most likely to be effective.

PMID- 22134063
TI  - Molecular cloning of LIM homeodomain transcription factor Lhx2 as a transcription
      factor of porcine follicle-stimulating hormone beta subunit (FSHbeta) gene.
AB  - We cloned the LIM-homeodomain protein LHX2 as a transcription factor for the
      porcine follicle-stimulating hormone beta subunit gene (Fshbeta) by the Yeast One
      Hybrid Cloning System using the upstream region of -852/-746 bases (b) from the
      transcription start site, called Fd2, as a bait sequence. The reporter assay in
      LbetaT2 and CHO cells revealed the presence of an LHX2-responsive region other
      than Fd2. A potential LHX2 binding sequence was confirmed as AATTAAT containing a
      consensus homeodomain binding core sequence AATT by Systematic Evolution of
      Ligands by Exponential Enrichment analysis. DNase I footprinting demonstrated
      three AATTAAT sequences located at regions -835/-829, -818/-812 and -806/-800 b
      in the Fd2 region and 12 binding sites in the distal and proximal regions mostly
      containing an AATT-core sequence. RT-PCR analysis of Lhx2 expression during
      porcine fetal and postnatal pituitary development showed a gradual increase from
      fetal day (f) 40 to postnatal day (p) 8 followed by a slight decrease to p230,
      suggesting that LHX2 may play its role largely in the late fetal and postnatal
      periods. The analyses of Lhx2 expression in pituitary tumor-derived cell lines
      showed their expressions in cell lines including alphaT31, LbetaT2 and others.
      Since LHX2 was previously identified as a transcription factor for Cga and the in
      vitro experiments in the present study suggested that LHX2 regulated the
      expression of Fshbeta, it is possible that LHX2 controls the synthesis of FSH at
      the transcription level.

PMID- 22134064
TI  - Effects of repetitive ionomycin treatment on in vitro development of bovine
      somatic cell nuclear transfer embryos.
AB  - To artificially activate embryos in somatic cell nuclear transfer (SCNT),
      chemical treatment with ionomycin has been used to induce transient levels of
      Ca(2+) and initiate reprogramming of embryos. Ca(2+) oscillation occurs naturally
      several times after fertilization (several times with 15- to 30-min intervals).
      This indicates how essential additional Ca(2+) influx is for successful
      reprogramming of embryos. Hence, in this report, the experimental design was
      aimed at improving the developmental efficiency of cloned embryos by repetitive
      Ca(2+) transients rather than the commonly used ionomycin treatment (4 min). To
      determine optimal Ca(2+) inflow conditions, we performed three different
      repetitive ionomycin (10 uM) treatments in reconstructed embryos: Group 1 (4-min
      ionomycin treatment, once), Group 2 (30-sec treatment, 4 times, 15-min intervals)
      and Group 3 (1-min treatment, 4 times, 15-min intervals). Pronuclear formation
      rates were checked to assess the effects of repetitive ionomycin treatment on
      reprogramming of cloned embryos. Cleavage rates were investigated on day 2, and
      the formation rates of blastocysts (BLs) were examined on day 7 to demonstrate
      the positive effect of repeated ionomycin treatment. In Group 3, a significant
      increase in BL formation was observed [47/200 (23.50%), 44/197 (22.33%) and
      69/195 (35.38%) in Groups 1, 2 and 3, respectively]. Culturing embryos with
      different ionomycin treatments caused no significant difference among the groups
      in terms of the total cell number of BLs (164.3, 158.5 and 145.1, respectively).
      Additionally, expression of the anti-apoptotic Bcl-2 gene and MnSOD increased
      significantly in Group 3, whereas the expression of the pro-apoptotic Bax
      decreased statistically. In conclusion, the present study demonstrated that
      repeated ionomycin treatment is an improved activation method that can increase
      the developmental competence of SCNT embryos by decreasing the incidence of
      apoptosis.

PMID- 22134065
TI  - A novel approach for analyzing fuzzy system reliability using different types of
      intuitionistic fuzzy failure rates of components.
AB  - This paper addresses the fuzzy system reliability analysis using different types
      of intuitionistic fuzzy numbers. Till now, in the literature, to analyze the
      fuzzy system reliability, it is assumed that the failure rates of all components
      of a system follow the same type of fuzzy set or intuitionistic fuzzy set.
      However, in practical problems, such type of situation rarely occurs. Therefore,
      in the present paper, a new algorithm has been introduced to construct the
      membership function and non-membership function of fuzzy reliability of a system
      having components following different types of intuitionistic fuzzy failure
      rates. Functions of intuitionistic fuzzy numbers are calculated to construct the
      membership function and non-membership function of fuzzy reliability via non
      linear programming techniques. Using the proposed algorithm, membership functions
      and non-membership functions of fuzzy reliability of a series system and a
      parallel systems are constructed. Our study generalizes the various works of the
      literature. Numerical examples are given to illustrate the proposed algorithm.

PMID- 22134066
TI  - Cellular oxidative stress and peroxisomal enzyme activities in pediatric liver
      transplant patients.
AB  - OBJECTIVES: In this study, we examined the activities of key peroxisomal enzymes
      in peripheral blood lymphocytes (PBLs) of pediatric liver transplant patients.
      SUBJECTS AND METHODS: Venous blood was drawn from 14 patients aged 5-16 years on
      FK-506 treatment and 18 healthy subjects for isolation of lymphocytes. beta
      Oxidation of very long chain fatty acids (VLCFAs) and activities of superoxide
      dismutase (SOD), glutathione peroxidase (GPx), NADPH oxidase (NOX), catalase and
      peroxisomal enzyme acyl CoA oxidase (ACO) were measured in cellular homogenates.
      Levels of malondialdehyde (MDA) were measured as an index of lipid peroxidation.
      Protein content and mRNA levels of catalase, peroxisomal membrane protein-70 (PMP
      70) and ACO were measured using Western blotting and PCR techniques. RESULTS:
      PBLs isolated from liver transplant patients showed significantly (p < 0.01)
      increased levels (226.9 +/- 24.5 MUmol/mg protein) of MDA as compared to the
      levels in controls (162.8 +/- 19.6 MUmol/mg protein), whereas enzyme activities
      of SOD and NOX remained unaltered in patients' cells. Enzyme activities of
      catalase and GPx were markedly (p < 0.01) decreased in cells isolated from liver
      transplant patients. ACO activity and beta-oxidation of VLCFAs in PBLs from liver
      transplant patients were however found to be significantly increased by 38 and
      52% respectively when compared with controls. Gene expression of PMP-70 and ACO
      was also significantly increased (p < 0.01) in PBLs of patients. CONCLUSION: Our
      results clearly showed that peroxisomal metabolic activities are markedly altered
      in lymphocytes of liver transplant patients and might contribute to the
      development of cellular oxidative stress.

PMID- 22134068
TI  - Expression profiling-based subtyping identifies novel non-small cell lung cancer
      subgroups and implicates putative resistance to pemetrexed therapy.
AB  - INTRODUCTION: A challenge of cancer therapy is to optimize therapeutical options
      to individual patients. Cancers with similar histology may show dramatically
      different responses to therapy, indicating that a refined approach needs to be
      developed to classify tumors by intrinsic characteristics that may predict
      response to chemotherapy. Global expression profile-based classification has the
      potential to identify such tumor-intrinsic subclasses. Pemetrexed effectiveness
      has been related to the expression of its target thymidylate synthase. The
      relatively frequent resistance of squamous cell carcinoma to Pemetrexed is
      correlated with high levels of thymidylate synthase expression. METHODS: A global
      expression profile-based molecular classification of non-small cell lung cancer
      (NSCLC) was performed. Gene expression was used to predict Pemetrexed
      responsiveness. The distinct molecular attributes of NSCLCs predicted likely to
      be resistant to Pemetrexed were bioinformatically characterized. We tested if
      routine immunohistochemical markers can be used to distinguish putative
      Pemetrexed responders, predicted by gene signatures, from nonresponders. RESULTS:
      Ninety NSCLCs were divided into six subclasses by gene expression signatures. The
      relevance of this novel phenotyping was linked to other tumor characteristics.
      Two of the subclasses correlated to putative Pemetrexed resistance. In addition,
      the identified signature genes characterizing putative Pemetrexed responsiveness
      predicted therapeutic benefit in a subset of squamous cell carcinoma.
      CONCLUSIONS: Gene expression signatures can be used to identify NSCLC subgroups
      and have potential to predict resistance to Pemetrexed therapy. We suggest that a
      combination of classical pathological markers can be used to identify molecular
      tumor subclasses associated with predicted Pemetrexed response.

PMID- 22134069
TI  - Thoroughness of mediastinal staging in stage IIIA non-small cell lung cancer.
AB  - INTRODUCTION: Guidelines recommend that patients with clinical stage IIIA non
      small cell lung cancer (NSCLC) undergo histologic confirmation of pathologic
      lymph nodes. Studies have suggested that invasive mediastinal staging is
      underutilized, although practice patterns have not been rigorously evaluated.
      METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare
      database to identify patients with stage IIIA NSCLC diagnosed from 1998 through
      2005. Invasive staging and use of positron emission tomography (PET) scanning
      were assessed using Medicare claims. Multivariable logistic regression was used
      to identify patient characteristics associated with use of invasive staging.
      RESULTS: Of 7583 stage IIIA NSCLC patients, 1678 (22%) underwent invasive
      staging. Patients who received curative intent cancer treatment were more likely
      to undergo invasive staging than patients who did not receive cancer-specific
      therapy (30% versus 9.8%, adjusted odds ratio, 3.31; 95% confidence interval,
      2.78-3.95). The oldest patients (age, 85-94 years) were less likely to receive
      invasive staging than the youngest (age, 67-69 years; 27.6% versus 11.9%; odds
      ratio, 0.46; 95% confidence interval, 0.34-0.61). Sex, marital status, income,
      and race were not associated with the use of the invasive staging. The use of
      invasive staging was stable throughout the study period, despite an increase in
      the use of PET scanning from less than 10% of patients before 2000 to almost 70%
      in 2005. CONCLUSION: Nearly 80% of Medicare beneficiaries with stage IIIA NSCLC
      do not receive guideline adherent mediastinal staging; this failure cannot be
      entirely explained by patient factors or a reliance on PET imaging. Incentives to
      encourage use of invasive staging may improve care.

PMID- 22134071
TI  - Risk factors for treatment-related death associated with chemotherapy and
      thoracic radiotherapy for lung cancer.
AB  - INTRODUCTION: The aim of the study is to evaluate the current status of treatment
      related death (TRD) in lung cancer patients. METHODS: We retrospectively analyzed
      the incidence and risk factors of TRD in lung cancer patients who received
      chemotherapy and/or thoracic radiotherapy using logistic regression analyses.
      RESULTS: Between January 2001 and December 2005, 1225 (222 small cell and 1003
      non-small cell lung cancers) patients received chemotherapy and/or thoracic
      radiotherapy as the initial treatment. Of these, 43 patients receiving
      chemotherapy followed by thoracic radiotherapy were included into both the
      chemotherapy-alone and radiotherapy-alone groups. There were a total of 23 (1.9%)
      TRDs. Chemotherapy-related deaths occurred in 7 of 927 (0.8%) patients, including
      4 from drug-induced lung injury, 2 from pneumonia, and 1 from unknown cause.
      Concurrent chemoradiotherapy-related deaths occurred in 12 of 245 (4.9%)
      patients, including 11 from radiation pneumonitis and 1 from pneumonia. Thoracic
      radiotherapy-related deaths occurred in 4 of 96 (4.2%) patients. The incidence of
      chemotherapy-related death was correlated with poor performance status (odds
      ratio [OR]: 11.4, 95% confidence interval [CI]: 3.53-37.1), the presence of
      hypoxia (OR: 19.3, CI: 6.06-61.7), hyponatremia (OR: 45.5, CI: 13.4-154), and
      treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (OR:
      8.56, CI: 2.48-29.5), whereas the incidence of concurrent chemoradiotherapy
      related death was correlated with pulmonary fibrosis (OR: 22.2, CI: 5.61-87.8).
      Radiotherapy results were not analyzed because there were too few patients.
      CONCLUSIONS: TRD occurred in 1.9% of the patients as a result of treatment
      related lung injury in the majority of the cases.

PMID- 22134070
TI  - Quality of life and symptom burden among long-term lung cancer survivors.
AB  - INTRODUCTION: Information is limited regarding health-related quality of life
      (QOL) status of long-term (greater than 5 years) lung cancer survivors (LTLCS).
      Obtaining knowledge about their QOL changes over time is a critical step toward
      improving poor and maintaining good QOL. The primary aim of this study was to
      conduct a 7-year longitudinal study in survivors of primary lung cancer which
      identified factors associated with either decline or improvement in QOL over
      time. METHODS: Between 1997 and 2003, 447 LTLCS were identified and followed
      through 2007 using validated questionnaires; data on overall QOL and specific
      symptoms were at two periods: short-term (less than 3 years) and long-term
      postdiagnosis. The main analyses were of clinically significant changes (greater
      than 10%) and factors associated with overall QOL and symptom burden for each
      period and for changes over time. RESULTS: Three hundred two (68%) underwent
      surgical resection only and 122 (27%) received surgical resection and
      radiation/chemotherapy. Recurrent or new lung malignancies were observed in 84
      (19%) survivors. Significant decline or improvement in overall QOL over time were
      reported in 155 (35%) and 67 (15%) of 447 survivors, respectively. Among the 155
      whose QOL declined, significantly worsened symptoms were fatigue (69%), pain
      (59%), dyspnea (58%), depressed appetite (49%), and coughing (42%). The symptom
      burden did not lessen among the 67 who reported improvement in overall QOL,
      suggesting that survivors had adapted to their compromised physical condition.
      CONCLUSIONS: LTLCS suffered substantial symptom burden that significantly
      impaired their QOL, indicating a need for targeted interventions to alleviate
      their symptoms.

PMID- 22134072
TI  - Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma.
AB  - INTRODUCTION: The EML4-anaplastic lymphoma kinase (ALK) translocation is a
      recognized oncogenic driver in non-small cell lung cancer. We investigated
      immunohistochemistry (IHC) screening with fluorescence in situ hybridization
      (FISH) confirmation for ALK detection and estimated the prevalence of ALK
      positivity in our patient cohort of never-smokers, together with differences in
      clinical outcomes and prognostic factors for patients with ALK-positive and ALK
      negative tumors. METHODS: We designed a three-phase study (training, validation,
      and testing) in 300 never-smokers with lung adenocarcinoma from the observational
      Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and
      concordance between the methods was assessed. Clinical outcomes were assessed via
      5-year progression- or recurrence-free survival from diagnosis. Prognostic
      factors for ALK-positive tumors and metastases were also investigated. RESULTS:
      ALK-positive patients were significantly (p < 0.05) younger and had higher grade
      tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed
      at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/-
      assessments, respectively. Five-year risk of progression or recurrence was
      doubled for patients with ALK-positive compared with ALK-negative tumors; ALK
      positive tumors also appeared to be associated with a higher risk of brain and
      liver metastases. CONCLUSIONS: Our findings suggest that ALK positivity is
      associated with a significantly poor outcome in nonsmoking-related adenocarcinoma
      and that ALK-positive tumors may be associated with an increased risk of brain
      and liver metastases compared with ALK-negative disease. Consequently, an unmet
      medical need exists in ALK-positive lung cancer patients, and effective ALK
      specific therapies are needed.

PMID- 22134074
TI  - Angular absorbed dose dependence of internal radiation-generating devices in
      radiotherapy.
AB  - The angular dependence of the absorbed dose from internal radiation-generating
      devices located within a tumor mass is investigated. Given the systematics of
      proton and heavy-ion differential scattering cross sections, candidate internal
      radiation-generating devices will have a relatively constant absorbed dose output
      beyond a critical angle. Inside this angle, the absorbed dose output is
      suppressed because elastic and inelastic differential cross sections are peaked
      in the beam direction. This peaking increases in severity as the particle energy
      increases and suggests internal radiation-generating devices must have a limited
      rotation capability to compensate for the depression in the absorbed dose for
      angles near the beam direction.

PMID- 22134075
TI  - Count rate limitations for pulse-counting instrumentation in pulsed accelerator
      fields.
AB  - This paper discusses various concepts involved in the counting losses of pulse
      counting health physics instrumentation when used within the pulsed radiation
      environments of typical accelerator fields in order to preestablish appropriate
      limitations in use. Discussed are the "narrow" pulse and the "wide" pulse cases,
      the special effect of neutron moderating assemblies, and the effect of pulse fine
      microstructure on the counting losses of the pulse-counting instrumentation. In
      the narrow-pulse case, the accelerator pulse width is less than or equal to the
      instrument's dead time; whereas in the wide-pulse case, the accelerator pulse
      width is significantly longer than the instrument's dead time. Examples are
      provided that highlight the various concepts and limitations.

PMID- 22134076
TI  - Reevaluation of waterborne releases of radioactive materials from the Mayak
      Production Association into the Techa River in 1949-1951.
AB  - The Mayak Production Association was the first site for the production of weapons
      grade plutonium in Russia. Early operations led to the waterborne release of
      radioactive materials into the small Techa River. Residents living downstream
      used river water for drinking and other purposes. The releases and subsequent
      flooding resulted in deposition of sediments along the shoreline and on
      floodplain soil. Primary routes of exposure were external dose from the deposited
      sediments and ingestion of 90Sr and other radionuclides. Study of the Techa River
      Cohort has revealed an increased incidence of leukemia and solid cancers.
      Epidemiologic studies are supported by extensive dose-reconstruction activities
      that have led to various versions of a Techa River Dosimetry System (TRDS). The
      correctness of the TRDS has been challenged by the allegation that releases of
      short-lived radionuclides were much larger than those used in the TRDS. Although
      the dosimetry system depends more upon measurements of 90Sr in humans and
      additional measurements of radionuclides and of exposure rates in the
      environment, a major activity has been undertaken to define more precisely the
      time-dependent rates of release and their radionuclide composition. The major
      releases occurred during 1950-1951 in the form of routine releases and major
      accidental releases. The reevaluated amount of total release is 114 PBq, about
      half of which was from accidents that occurred in late 1951. The time-dependent
      composition of the radionuclides released has also been reevaluated. The improved
      understanding presented in this paper is possible because of access to many
      documents not previously available.

PMID- 22134078
TI  - The use of FDTD in establishing in vitro experimentation conditions
      representative of lifelike cell phone radiation on the spermatozoa.
AB  - Recent studies have shown that exposing human semen samples to cell phone
      radiation leads to a significant decline in sperm parameters. In daily living, a
      cell phone is usually kept in proximity to the groin, such as in a trouser
      pocket, separated from the testes by multiple layers of tissue. The aim of this
      study was to calculate the distance between cell phone and semen sample to set up
      an in vitro experiment that can mimic real life conditions (cell phone in trouser
      pocket separated by multiple tissue layers). For this reason, a computational
      model of scrotal tissues was designed by considering these separating layers, the
      results of which were used in a series of simulations using the Finite Difference
      Time Domain (FDTD) method. To provide an equivalent effect of multiple tissue
      layers, these results showed that the distance between a cell phone and semen
      sample should be 0.8 cm to 1.8 cm greater than the anticipated distance between a
      cell phone and the testes.

PMID- 22134077
TI  - Identification of proteins secreted into the medium by human lymphocytes
      irradiated in vitro with or without adaptive environments.
AB  - There is increasing evidence to support the hypothesis of adaptive response, a
      phenomenon in which protection arises from a low-dose radiation (<0.1 Gy) against
      damage induced by subsequent exposure to high-dose radiation. The molecular
      mechanisms underlying such protection are poorly understood. The goal of this
      study was to fill this knowledge gap. Mass spectrometry-based proteomics was used
      to characterize global protein expression profiles in the medium collected from
      human lymphocyte cultures given sham irradiation (0 Gy) or a priming low dose of
      0.03 Gy 137Cs gamma rays 4 h prior to a challenging dose of 1 Gy 137Cs gamma
      rays. Adaptive response was determined by decreased micronucleus frequencies in
      lymphocytes receiving low dose irradiation prior to high dose irradiation
      compared to those receiving only high dose irradiation. Adaptive response was
      found in these experiments. Proteomic analysis of media revealed: (a) 55 proteins
      with similar abundance in both groups; (b) 23 proteins in both groups, but 7 of
      them were high abundance in medium with adaptive environment, while 16 high
      abundance proteins were in medium without adaptive environment; (c) 17 proteins
      in medium with adaptive environment only; and (d) 8 proteins in medium without
      adaptive environment only. The results provide a foundation for improving
      understanding of the molecular mechanisms associated with the beneficial effects
      of low dose radiation that, in turn, will have an important impact on radiation
      risk estimation. Hence, these studies are highly relevant to radiation protection
      due to an increased use of low dose radiation in daily life (e.g., medical
      diagnosis or airport safety) or an unavoidable exposure to low level background
      radiation.

PMID- 22134079
TI  - Uranium and trace elements in phosphate fertilizers--Saudi Arabia.
AB  - Manufactured phosphate fertilizers and their agricultural applications are
      considerable sources of environmental pollution. In this study, composite samples
      of phosphate fertilizer (PF) of different physical forms (granular, G, and water
      soluble powder, L) were collected. The activity concentration of 238U in Bq kg(
      1) was measured using gamma ray spectrometers, and the concentrations of arsenic,
      cadmium, copper, lead and selenium in mg kg(-1) were measured using inductively
      coupled plasma optical emission spectrometers (ICP-OES). The main aims of this
      study were to evaluate PF quality according to its physical form, determine
      manufacturers (local, L, or imported, I), and estimate the hazardous impacts of
      long-term phosphate fertilization. There was significant variation in the
      concentration of uranium and other elements in PF samples. In order to have
      globally normalized data, it is highly recommended to express the concentration
      of trace elements as per phosphorus mass instead of fertilizer mass. The annual
      addition of these elements to soil due to phosphate fertilization was calculated.
      The possible accumulation of added uranium and other trace elements due to
      fertilization in the subsurface soil layer and/or shallow underground water
      should be studied in the soil environment of Saudi Arabia.

PMID- 22134080
TI  - Evaluation of scattered radiation in a calibration range using exposure rate
      energy spectra.
AB  - ISO standard 4037 specifies that for calibrating protection level dosimeters,
      scattered radiation should contribute less than 5% of the exposure. In previous
      work, the authors reported the results of an MCNP analysis of the shadow shield
      technique that was performed for a calibration range with a Cs irradiator. This
      paper examines the energy distribution of the photons contributing to the
      exposure percent scatter (S%) and the detailed origin of the scatter that
      originates in the irradiator. In summary, it reports that: 1) the majority of S%
      is due to photons with energies that are significantly below the source energy,
      2) a significant percentage of S% is due to photons that scatter within the
      source and source capsule walls, and 3) S% due to scatter within the irradiator
      is even more significant than previously reported.

PMID- 22134081
TI  - ICNIRP statement--Health issues associated with millimeter wave whole body
      imaging technology.

PMID- 22134082
TI  - Revised requirements for radiation emergency bioassay techniques for the public
      and first responders.
AB  - This technical note reports the required sensitivities for bioassay techniques
      derived from a 0.1 Sv effective dose incurred in the first year following an
      emergency (recommended by ICRP) and those derived from a 0.25 Sv committed
      effective dose (recommended by NCRP) as dose thresholds for possible medical
      attention. During a large-scale radiological or nuclear emergency, the dose
      threshold chosen for medical attention may be raised, as available resources may
      be insufficient for conducting a sensitive contamination assessment and medical
      treatment of a large population exposed to radioactive contamination.

PMID- 22134083
TI  - Investigation of 238U content in bottled water consumed in Kuwait and estimates
      of annual effective doses.
AB  - A study of the 238U content in bottled water consumed in Kuwait was performed.
      The bottled water samples originated from 16 different countries. Of the 41
      investigated samples, 238U was detected in 23 samples in which the radionuclide's
      activity was determined. Consequently, it was found that activity levels of all
      samples were several of orders of magnitude below the guidance limits. Moreover,
      annual effective doses were estimated for three age groups, namely adults,
      children, and infants. As a result, it was found that the doses received by all
      age groups were several of orders of magnitude below the guideline levels. Hence,
      consumption of bottled water sold in Kuwait is safe for the presence of 238U.

PMID- 22134084
TI  - Radar commentary: Use of linear no-threshold hypothesis in radiation protection
      regulation in the United States.
AB  - Radiation protection recommendations advanced by the International Commission on
      Radiological Protection and National Council on Radiation Protection and
      Measurements, and many times adopted into regulations by the United States
      Nuclear Regulatory Commission, need to be based on scientifically justified
      assumptions and conclusions. The linear no-threshold model assigns risk to every
      radiation exposure above zero dose and is the current basis for setting radiation
      protection standards worldwide. This hypothesis is vigorously challenged by many
      individuals but just as vigorously defended in spite of the uncertainties
      surrounding health effects at low dose levels. It is clear that at radiation
      doses below 100 mSv, the effects, if any, are so low as to be unobservable and
      perhaps, therefore, unknowable. However, the linear no-threshold hypothesis is
      used routinely to formulate regulatory dose limits for workers and the general
      public and to derive stochastic radiogenic risk estimates at low doses. This note
      will show that while the linear no-threshold hypothesis may play a legitimate
      role in setting radiation protection standards and operating policies, such as
      establishing dose limits or as part of an operational "as low as is reasonably
      achievable" (ALARA) policy, it is inappropriate for use in estimating possible
      cancer risks associated with low-level radiation exposures. It will also
      demonstrate that the raising, not lowering, of current regulatory dose limits is
      more solidly supported by the actual observed data on radiation dose and effects.
      The authors submit that the misuse of the linear no-threshold model for
      predicting radiation effects in exposed individuals and populations should be
      discontinued.

PMID- 22134089
TI  - Transmembrane alpha-helix 2 and 7 are important for small molecule-mediated
      activation of the GLP-1 receptor.
AB  - Glucagon-like peptide-1 (GLP-1) activates the GLP-1 receptor (GLP-1R), which
      belongs to family B of the G-protein-coupled receptors. We previously identified
      a selective small molecule ligand, compound 2, that acted as a full agonist and
      allosteric modulator of GLP-1R. In this study, the structurally related small
      molecule, compound 3, stimulated cAMP production from GLP-1R, but not from the
      homologous glucagon receptor (GluR). The receptor selectivity encouraged a
      chimeric receptor approach to identify domains important for compound 3-mediated
      activation of GLP-1R. A subsegment of the GLP-1R transmembrane domain containing
      TM2 to TM5 was sufficient to transfer compound 3 responsiveness to GluR.
      Therefore, divergent residues in this subsegment of GLP-1R and GluR are
      responsible for the receptor selectivity of compound 3. Functional analyses of
      other chimeric receptors suggested that the existence of a helix-helix interface
      between TM1 and TM7 is important for the compound 3 response. Furthermore, site
      directed mutagenesis revealed that a Phe195-Leu substitution in TM2 and a Thr391
      Ala substitution in TM7 increased and decreased the efficacy of compound 3
      without disturbing the potency or efficacy of GLP-1. Collectively, differential
      effects of receptor mutations suggest that TM2 and/or TM7 are important for
      compound 3-mediated activation of GLP-1R.

PMID- 22134088
TI  - Channeling dysglycemia: ion-channel variations perturbing glucose homeostasis.
AB  - Maintaining blood glucose homeostasis is a complex process that depends on
      pancreatic islet hormone secretion. Hormone secretion from islets is coupled to
      calcium entry which results from regenerative islet cell electrical activity.
      Therefore, the ionic mechanisms that regulate calcium entry into islet cells are
      crucial for maintaining normal glucose homeostasis. Genome-wide association
      studies (GWAS) have identified single-nucleotide polymorphisms (SNPs), including
      five located in or near ion-channel or associated subunit genes, which show an
      association with human diseases characterized by dysglycemia. This review focuses
      on polymorphisms and mutations in ion-channel genes that are associated with
      perturbations in human glucose homeostasis and discusses their potential roles in
      modulating pancreatic islet hormone secretion.

PMID- 22134091
TI  - A mutation of the fission yeast EB1 overcomes negative regulation by
      phosphorylation and stabilizes microtubules.
AB  - Mal3 is a fission yeast homolog of EB1, a plus-end tracking protein (+TIP). We
      have generated a mutation (89R) replacing glutamine with arginine in the calponin
      homology (CH) domain of Mal3. Analysis of the 89R mutant in vitro has revealed
      that the mutation confers a higher affinity to microtubules and enhances the
      intrinsic activity to promote the microtubule-assembly. The mutant Mal3 is no
      longer a +TIP, but binds strongly the microtubule lattice. Live cell imaging has
      revealed that while the wild type Mal3 proteins dissociate from the tip of the
      growing microtubules before the onset of shrinkage, the mutant Mal3 proteins
      persist on microtubules and reduces a rate of shrinkage after a longer pausing
      period. Consequently, the mutant Mal3 proteins cause abnormal elongation of
      microtubules composing the spindle and aster. Mal3 is phosphorylated at a cluster
      of serine/threonine residues in the linker connecting the CH and EB1-like C
      terminal motif domains. The phosphorylation occurs in a microtubule-dependent
      manner and reduces the affinity of Mal3 to microtubules. We propose that because
      the 89R mutation is resistant to the effect of phosphorylation, it can associate
      persistently with microtubules and confers a stronger stability of microtubules
      likely by reinforcing the cylindrical structure.

PMID- 22134092
TI  - Porcine circovirus type 2 explores the autophagic machinery for replication in PK
      15 cells.
AB  - Porcine circovirus type 2 (PCV2), an important pathogen of pigs, causes lymphoid
      depletion in infected tissues most probably by inducing apoptosis although the
      precise pathogenesis of PCV2-associated diseases remains unknown. We speculate
      whether autophagy, another cellular response to stress or infections by bacterial
      or viral pathogens, is involved in PCV2 infection. Here, we provide the first
      evidence that PCV2 could trigger autophagosome formation and enhance autophagic
      flux in PK-15 cells, most likely by its capsid protein. Using activators or
      inhibitors including siRNA targeting atg5, autophagy was found to enhance viral
      replication and capsid protein expression. These results suggest that PCV2 might
      employ the autophagy machinery to enhance its replication in host cells, thus
      raising the possibility of targeting autophagic pathway as a potential antiviral
      strategy against PCV2 infection.

PMID- 22134093
TI  - Polymorphisms and noncardioembolic stroke in three case-control studies.
AB  - BACKGROUND: Gene variants associated with disease could reveal novel mechanisms.
      We searched for single nucleotide polymorphisms (SNPs) associated with
      noncardioembolic stroke (nonCES). METHODS: We tested 24,926 SNPs in or near genes
      for association with nonCES in the Vienna Study (551 cases, 815 controls) and
      then evaluated the associated SNPs in the UCSF-CC Study (570 cases, 1,604
      controls) first in pooled DNA samples and then in individual DNA samples. We then
      asked whether the risk alleles of the SNPs associated with increased risk in both
      studies were also associated with increased risk of nonCES in the German Study
      (728 cases, 1,041 controls). RESULTS: Six of the 46 SNPs that were associated
      with nonCES in both the Vienna and the UCSF-CC Studies were also associated with
      nonCES in the German Study: rs362277 in HTT (OR 1.39, 90% CI 1.12-1.71),
      rs2924914 near CSMD1 (OR 1.22, 90% CI 1.04-1.43), rs1264352 near DDR1 (OR 1.20,
      90% CI 1.02-1.41), rs544115 in NEU3 (OR 1.63, 90% CI 1.02-2.62), rs12481805 in
      UMODL1 (OR 1.31, 90% CI 1.01-1.81), and rs2857595 near NCR3 (OR 1.15, 90% CI 1.00
      1.32). Accounting for multiple testing of 46 SNPs, these 6 SNPs had a false
      discovery rate of 0.69. CONCLUSIONS: Some of the 6 SNPs may be associated with
      nonCES but most may be false positives. These 6 SNPs merit investigation in
      additional nonCES study populations.

PMID- 22134094
TI  - Improved modeling of clinical data with kernel methods.
AB  - OBJECTIVE: Despite the rise of high-throughput technologies, clinical data such
      as age, gender and medical history guide clinical management for most diseases
      and examinations. To improve clinical management, available patient information
      should be fully exploited. This requires appropriate modeling of relevant
      parameters. METHODS: When kernel methods are used, traditional kernel functions
      such as the linear kernel are often applied to the set of clinical parameters.
      These kernel functions, however, have their disadvantages due to the specific
      characteristics of clinical data, being a mix of variable types with each
      variable its own range. We propose a new kernel function specifically adapted to
      the characteristics of clinical data. RESULTS: The clinical kernel function
      provides a better representation of patients' similarity by equalizing the
      influence of all variables and taking into account the range r of the variables.
      Moreover, it is robust with respect to changes in r. Incorporated in a least
      squares support vector machine, the new kernel function results in significantly
      improved diagnosis, prognosis and prediction of therapy response. This is
      illustrated on four clinical data sets within gynecology, with an average
      increase in test area under the ROC curve (AUC) of 0.023, 0.021, 0.122 and 0.019,
      respectively. Moreover, when combining clinical parameters and expression data in
      three case studies on breast cancer, results improved overall with use of the new
      kernel function and when considering both data types in a weighted fashion, with
      a larger weight assigned to the clinical parameters. The increase in AUC with
      respect to a standard kernel function and/or unweighted data combination was
      maximum 0.127, 0.042 and 0.118 for the three case studies. CONCLUSION: For
      clinical data consisting of variables of different types, the proposed kernel
      function--which takes into account the type and range of each variable--has shown
      to be a better alternative for linear and non-linear classification problems.

PMID- 22134095
TI  - Prediction of human major histocompatibility complex class II binding peptides by
      continuous kernel discrimination method.
AB  - OBJECTIVE: Accurate prediction of major histocompatibility complex (MHC) class II
      binding peptides helps reducing the experimental cost for identifying helper T
      cell epitopes, which has been a challenging problem partly because of the
      variable length of the binding peptides. This work is to develop an accurate
      model for predicting MHC-binding peptides using machine learning methods.
      METHODS: In this work, a machine learning method, continuous kernel
      discrimination (CKD), was used for predicting MHC class II binders of variable
      lengths. The composition transition and distribution features were used for
      encoding peptide sequence and the Metropolis Monte Carlo simulated annealing
      approach was used for feature selection. RESULTS: Feature selection was found to
      significantly improve the performance of the model. For benchmark dataset Dataset
      1, the number of features is reduced from 147 to 24 and the area under the
      receiver operating characteristic curve (AUC) is improved from 0.8088 to 0.9034,
      while for benchmark dataset Dataset-2, the number of features is reduced from 147
      to 44 and the AUC is improved from 0.7349 to 0.8499. An optimal CKD model was
      derived from the feature selection and bandwidth optimization using 10-fold cross
      validation. Its AUC values are between 0.831 and 0.980 evaluated on benchmark
      datasets BM-Set1 and are between 0.806 and 0.949 on benchmark datasets BM-Set2
      for MHC class II alleles. These results indicate a significantly better
      performance for our CKD model over other earlier models based on the training and
      testing of the same datasets. CONCLUSIONS: Our study suggested that the CKD
      method outperforms other machine learning methods proposed earlier in the
      prediction of MHC class II biding peptides. Moreover, the choice of the cut-off
      for CKD classifier is crucial for its performance.

PMID- 22134096
TI  - Epilepsy in the Twitter era: a need to re-tweet the way we think about seizures.
AB  - Seizures have long been associated with misconceptions and stigma. Exponential
      growth in Internet use has seen the rapid expansion of social media, such as
      Twitter, for health promotion. In view of the popularity of Twitter, we sought to
      explore how seizures are being portrayed on this social networking website and to
      consider its potential for information dissemination. A 48-hour Twitter search
      was used as a preliminary data set to determine an appropriate classification
      scheme of "seizure"-related posts ("tweets"). Analysis was then conducted using
      "seizure" tweets from a 7-consecutive day sample period. Tweets were analyzed and
      coded by two independent reviewers. Predominant categories were Metaphorical
      (32%), Personal Accounts (31%), Informative (12%), and Ridicule/Joke (9%). This
      study supports the notion that stigmatization associated with seizures continues
      to flourish, as 41% of "seizure" tweets were derogatory in nature. Although
      Twitter could be used to disseminate accurate information on seizures and
      epilepsy, this study suggests that it is currently propagating negative attitudes
      toward seizures with potential for fueling stigma. In recent years there have
      been significant advancements in technology offering many new methods of sharing
      information. Social networking sites allow real-time communication while
      providing the opportunity for exchange of information and opinions. Twitter, a
      website launched in 2006, allows users to communicate through "tweets" limited to
      140 characters. Twitter's popularity has drastically increased since its
      inception, with approximately 110 million tweets per day from 200 million users
      worldwide, as of January 2011
      (http://blogs.forbes.com/oliverchiang/2011/01/19/twitter-hits-nearly-200m-users
      110m-tweets-per-day-focuses-on-global-expansion/). Such social media facilitate
      communication about an array of health-related topics including seizures and
      epilepsy.

PMID- 22134097
TI  - Evidence-based models of care for people with epilepsy.
AB  - Advances in medical science and technology, together with improved medical and
      nursing care, are continuously improving health outcomes in chronic illness,
      including epilepsy. The consequent increasing diagnostic and therapeutic
      complexity is placing a burgeoning strain on health care systems. In response, an
      international move to transform chronic disease management (CDM) aims to optimize
      the quality and safety of care while containing health care costs. CDM models
      recommend: integration of care across organizational boundaries that is supported
      with information and communication technology; patient self-management; and
      guideline implementation to promote standardized care. Evidence of the
      effectiveness of CDM models in epilepsy care is presented in this review article.

PMID- 22134098
TI  - Seizure recency and quality of life in adolescents with childhood-onset epilepsy.
AB  - Health-related quality of life (HRQOL) is associated with seizure recency among
      adults with epilepsy. In a prospective, community-based study of long-term
      outcomes of childhood-onset epilepsy, we evaluated whether worse HRQOL is
      associated with more recent seizures among children and adolescents with
      epilepsy. We used the Child Health Questionnaire (CHQ), a generic measure with
      child and parent-proxy versions, to measure HRQOL. Among 277 children with
      epilepsy (CWE) assessed 9 years after diagnosis, parent-proxy reported but not
      child self-reported HRQOL was significantly worse for those having seizures in
      the prior year than for those who were seizure free >=1 year across the majority
      of scales. There were no differences between CWE in remission for 1-5 years and
      those seizure free >=5 years for child and parent-proxy reported HRQOL with the
      exception of the parent Emotional Impact scale, suggesting that HRQOL differences
      related to seizure recency level off after the initial year of remission.

PMID- 22134099
TI  - Increased frequency of congenital heart defects in Menkes disease.
AB  - ATP7A is a copper-transporting ATPase critical for central and peripheral nervous
      system function. Mutations in ATP7A cause Menkes disease and occipital horn
      syndrome (OHS), allelic X-linked recessive conditions that feature vascular
      abnormalities ascribed to low activity of lysyl oxidase, a copper-dependent
      enzyme. From a recently created Menkes disease/OHS patient registry, we
      identified four of 95 patients with major congenital heart defects (4.2%), a
      proportion exceeding the general population prevalence (~1%). In conjunction with
      mouse models of Menkes disease, OHS, and lysyl oxidase deficiency (which feature
      aortic aneurysms, irregular attachment between vascular endothelium and mesoderm,
      and other defects of embryological development) our observation suggests an
      important role of copper metabolism in cardiac development. Congenital heart
      disease may be an under-appreciated abnormality in Menkes disease, and should be
      considered in a broad differential diagnosis of cardiac defects found prenatally
      in male fetuses. Conversely, newborn infants with suspected or confirmed Menkes
      disease should be evaluated for heart disease by careful clinical examination and
      echocardiography, if indicated.

PMID- 22134101
TI  - Three-dimensional topological insulator in a magnetic field: chiral side surface
      states and quantized Hall conductance.
AB  - Low energy excitation of surface states of a three-dimensional topological
      insulator (3DTI) can be described by Dirac fermions. By using a tight-binding
      model, the transport properties of the surface states in a uniform magnetic field
      are investigated. It is found that chiral surface states parallel to the magnetic
      field are responsible for the quantized Hall (QH) conductance (2n + 1)e2/h
      multiplied by the number of Dirac cones. Due to the two-dimensional nature of the
      surface states, the robustness of the QH conductance against impurity scattering
      is determined by the oddness and evenness of the Dirac cone number. An
      experimental setup for transport measurement is proposed.

PMID- 22134100
TI  - Different response rates between palmoplantar involvement and diffuse plaque
      psoriasis in patients treated with infliximab.

PMID- 22134102
TI  - Validation of a HPLC-tandem MS/MS method for pharmacokinetics study of (+)
      pinoresinol-di-beta-D-glucopyranoside from Eucommia ulmoides Oliv extract in
      rats' plasma.
AB  - Natural plant compounds have an unexceptional influence in pharmacy as they
      provide an uncountable number of invaluable lead molecules. Phytochemical
      researches nowadays focus on bio-assay guided revealing of the therapeutic
      profile and synergism of medicinal herbs and their constituents. Assessing the
      clinical and biological potential and determining the pharmacokinetics of herbal
      constituents is also an area of much interest. This work was conducted in order
      to carry out a sensitive liquid chromatography tandem mass spectrum (HPLC-MS/MS)
      method for the pharmacokinetics study of (+)-pinoresinol-di-beta-D
      glucopyranoside (PG) in rats' plasma after oral administration of Eucommia
      ulmoides Oliv extract. The validated method was by means of linearity, precision,
      matrix effect and recovery so that it could be used for the pharmacokinetic study
      of PG. The obtained pharmacokinetic parameters shown that PG pertains to one
      compartment model and 95% of PG was eliminated within 12h.

PMID- 22134103
TI  - Old findings in multiple sclerosis but a new application.

PMID- 22134104
TI  - Vasculitis of the central and peripheral nervous system mimicking brain death.

PMID- 22134105
TI  - Forecasts aid HABs response.

PMID- 22134106
TI  - ABCB1 haplotype is associated with major molecular response in chronic myeloid
      leukemia patients treated with standard-dose of imatinib.
AB  - BACKGROUND: Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor used
      for treating chronic myeloid leukemia (CML). IM has high efficacy, however some
      individuals develop a resistance due to impaired bioavailability. Polymorphisms
      in genes encoding membrane transporters such as ABCB1 have been associated with
      differences in protein expression and function that influence the response to
      several drugs. AIM: To investigate the relationship of ABCB1 polymorphisms with
      markers of response to IM in patients with CML. METHODS: One hundred eighteen CML
      patients initially treated with a standard dose of IM (400mg/day) for 18months
      were selected at two health centers in Sao Paulo City, Brazil. The response
      criteria were based on the European LeukemiaNet recommendations. ABCB1
      polymorphisms c.1236C>T (rs1128503), c.3435C>T (rs1045642) and c.2677G>T/A
      (rs2032582) were evaluated by PCR-RFLP. RESULTS: ABCB1 polymorphisms were not
      related with a risk for CML in this sample population (p<0.05). In the CML group,
      frequencies of ABCB1 SNPs were similar between responder and non-responder
      patients (p>0.05). In the responder group, the frequency of
      ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular
      response (MMR) (51.7%) than in patients without MMR (8.3%, p=0.010). Furthermore,
      carriers of this haplotype had increased the probability of reaching the MMR
      compared with the non-carriers (OR: 11.8; 95% CI: 1.43-97.3, p=0.022).
      CONCLUSIONS: The ABCB1 1236CT/2677GT/3435CT haplotype is positively associated
      with the major molecular response to IM in CML patients.

PMID- 22134108
TI  - Slow recovery of blood glucose in the insulin tolerance test during the prepartum
      transition period negatively impacts the nutritional status and reproductive
      performance postpartum of dairy cows.
AB  - In peripartum dairy cows, insulin resistance (IR) increases to adjust the
      direction of energy to lactation after calving. To investigate the effect of
      prepartum IR on postpartum reproductive performance, the insulin tolerance test
      (ITT) was applied to 15 cows at 3 weeks (Pre21) and 10 days (Pre10) before the
      predicted calving date. Blood glucose area under the curve (AUC(glu)) within 120
      min after administration of 0.05 IU/kg-BW insulin was calculated. The occurrence
      of first ovulation, days to first artificial insemination (AI) and first AI
      conception rate were recorded. Nutritional status postpartum was evaluated by
      blood chemical analysis. Based on AUC(glu) changes from Pre21 to Pre10, cows were
      classified into either the AUC-up group (AUC(glu) increase, n=5) or the AUC-down
      group (AUC(glu) decrease, n=10). There was no difference in the decrease in blood
      glucose at 30 min after insulin injection between groups, although glucose
      recovery from 30 to 60 min during the ITT was slow at Pre10 in the AUC-up group.
      The AUC-up group had a higher number of days to first AI and high glucose, total
      protein, globulin, gamma-glutamyltransferase, triacylglycerol levels and a low
      albumin-globulin ratio at the 14th day postpartum. The present study infers that
      prepartum slow glucose recovery rather than insulin sensitivity might increase
      the potential for subclinical health problems postpartum and thus suppress
      reproductive performance. During the prepartum transition period, glucose
      dynamics in the ITT can be considered as a new indicator for the postpartum
      metabolic status and reproductive performance of dairy cows.

PMID- 22134109
TI  - Bilateral microphthalmia and aphakia associated with multiple eye abnormalities
      in a free-living European red deer calf (Cervus elaphus).
AB  - A free-living European red deer calf (Cervus elaphus) was euthanized due to
      bilateral microphthalmia. Lens was missing, replaced by proliferating squamous
      epithelial cells; hyperplastic squamous cells, sebaceous and mucinous glands were
      observed within the cornea with the characteristics of inclusion cyst. Findings
      were consistent with congenital microphthalmia/aphakia, with multiple eye
      abnormalities.

PMID- 22134110
TI  - Simultaneous estimation of the pH of rumen and reticulum fluids of cows using a
      radio-transmission pH-measurement system.
AB  - Circadian pH changes in the fluid of the rumen (bottom and middle) and reticulum
      were assessed simultaneously using wireless and wired radio-transmission pH
      measurement systems in cows fed a control diet (C diet) or rumen-acidosis
      inducing diet (RAI diet). The pH in the three sites decreased following the
      morning and evening feedings. In cows fed the C diet, the bottom-rumen and
      reticular pH reverted to the basal level by the next morning, while the middle
      rumen pH did not recover completely, suggesting that active fermentation occurred
      in the middle of the rumen. The mean pH at 1 hr intervals was higher in the
      reticulum than at the bottom and in the middle of the rumen. The relatively
      stable reticular pH may result from dilution due to salivation. In cows fed the
      RAI diet, the bottom-rumen pH fell to approximately 5.2 after the evening
      feeding, but returned to the basal level by the next morning. In contrast, the
      middle-rumen pH did not return to the basal level (6.5) within 24 hr, presumably
      owing to continuous, vigorous fermentation. There were positive correlations
      between the pH at the bottom and in the middle of the rumen and at the bottom of
      the rumen and in the reticulum. These findings indicate that our radio
      transmission pH-measurement system may be suitable tool for simultaneous
      measurement of pH in the rumen and reticulum fluid.

PMID- 22134107
TI  - Hematologically important mutations: leukocyte adhesion deficiency (first
      update).
AB  - Leukocyte adhesion deficiency (LAD) is an immunodeficiency caused by defects in
      the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As
      a result, patients with LAD suffer from severe bacterial infections and impaired
      wound healing, accompanied by neutrophilia. In LAD-I, mutations are found in
      ITGB2, the gene that encodes the beta subunit of the beta(2) integrins. This
      syndrome is characterized directly after birth by delayed separation of the
      umbilical cord. In the rare LAD-II disease, the fucosylation of selectin ligands
      is disturbed, caused by mutations in SLC35C1, the gene that encodes a GDP-fucose
      transporter of the Golgi system. LAD-II patients lack the H and Lewis Le(a) and
      Le(b) blood group antigens. Finally, in LAD-III (also called LAD-I/variant) the
      conformational activation of the hematopoietically expressed beta integrins is
      disturbed, leading to leukocyte and platelet dysfunction. This last syndrome is
      caused by mutations in FERMT3, encoding the kindlin-3 protein in all blood cells
      that is involved in the regulation of beta integrin conformation.

PMID- 22134111
TI  - Morphological study in B16F10 murine melanoma cells after photodynamic
      hyperthermal therapy with indocyanine green (ICG).
AB  - Photodynamic hyperthermal therapy (PHT) with indocyanine green (ICG) is a
      combination of photodynamic therapy (PDT) and hyperthermia (HT). The low toxicity
      of ICG with an absorption wavelength of 700-800 nm is thought to make it a good
      candidate as a photosensitizer for PHT. Upon irradiation, ICG produces oxygen
      radicals and generates heat. The optimal concentration of ICG and the PHT post
      irradiation time effects were evaluated by the cytotoxicity of the treatment on
      B16F10 murine melanoma. The cytotoxicity of PHT was determined based on the
      morphology of apoptotic and necrotic cells under phase-contrast microscope,
      confocal laser scanning microscope (CLSM) with DAPI and Annexin V-FITC/PI double
      staining, and cell surface structure evaluation by scanning electron microscopy
      (SEM). The use of ICG at a concentration of 150 uM was selected, as cell
      proliferation was inhibited from 0 to 24 hr post-PHT with a 3-fold decrease in
      cell viability (P<0.001) compared to the control group. A morphological
      observation revealed apoptotic and some degree of necrotic features in the PHT
      treated cells.

PMID- 22134112
TI  - Turkish women's self-reported knowledge and behavior towards oral health during
      pregnancy.
AB  - OBJECTIVES: The purpose of this study was to evaluate oral health care knowledge
      and behavior of women during pregnancy. SUBJECTS AND METHODS: The study
      population consisted of 351 mothers with children under 3 months of age who
      presented at Gulhane Medical Academy's Department of Pediatrics for a routine
      child check-up. Mothers were asked to complete a questionnaire about their
      knowledge and behavior regarding dental care during pregnancy. RESULTS: All the
      women who participated in the study had dental insurance, and most of them had
      high levels of education. Of the 351 mothers, 263 (75%) had heard about possible
      connections between oral health and pregnancy outcome, and 165 (47%) believed
      tooth and periodontal problems could affect pregnancy outcome. However, 256 (73%)
      women still believed that calcium would be drawn out of their teeth by the
      developing baby, and 151 (43%) believed in the erroneous statement 'A tooth for a
      baby'. 241 (68.7%) women had experienced oral health problems during pregnancy;
      however, only 48 (13.7%) visited a dentist during their pregnancy. CONCLUSIONS:
      Turkish women, despite having knowledge that adverse pregnancy events may be
      related to dental and periodontal problems, did not seek oral health care during
      pregnancy. This suggests the need to better educate medical providers to inform
      pregnant women to obtain oral health care during pregnancy.

PMID- 22134113
TI  - Diagnostic value of ischaemia-modified albumin in pulmonary contusion in rats.
AB  - BACKGROUND: Patients with pulmonary contusion (PC) are at increased risk of
      development of complications and death after trauma. The early diagnosis and
      determination of severity of PC could improve clinical outcomes. The aim of the
      study was to determine the diagnostic value of ischaemia-modified albumin (IMA)
      in a PC model in rats. METHODS: Thirty-two Sprague-Dawley rats were randomly
      allocated to four groups; the uninjured control Group I (n=7) and the uninjured
      control Group II (n=7) were euthanised at 2 and 6h, respectively, and PC groups
      III (n=9) and IV (n=9) were euthanised at 2 and 6h after trauma, respectively.
      The serum level of IMA, tissue and serum malondialdehyde (MDA) levels, and
      histopathological damage scores of the lung tissue were determined. RESULTS:
      Serum IMA and lung tissue MDA levels in the PC groups were not significantly
      different to those of the control groups (p=0.555; p=0.086, respectively). Serum
      MDA levels were significantly higher in the PC groups than in the control groups
      (p=0.011). When histopathological changes in lung parenchyma were evaluated,
      there was a statistical difference between the injured and uninjured groups for
      inflammation and lung injury (p=0.017; p=0.001, respectively). However, there was
      no significant correlation between the histopathological score and biochemical
      parameters. CONCLUSION: Our preliminary findings suggest that there is no
      significant change of serum IMA levels in the acute phase of PC induced by blunt
      chest trauma.

PMID- 22134114
TI  - Radiological evaluation of intertrochanteric fracture fixation by the proximal
      femoral nail.
AB  - BACKGROUND: Successful treatment of intertrochanteric femoral fractures was
      reportedly influenced by the position of the fixation devices, by reduction
      quality and by fracture type. METHODS: The records of 227 patients with
      intertrochanteric fractures treated by intramedullary hip screws were analysed
      retrospectively. The angle and distance from the femur head apex were transformed
      into Cartesian coordinates. Comparisons were performed between patients with no
      mechanical failure (207 patients, 90.7%), with cutouts (15 patients, 6.6%) and
      with secondary loss of reduction (5 patients, 2.2%). RESULTS: The standard tip
      apex distance (TAD) measurement above 25 mm did not predict failure (p=0.62).
      Mechanical failure rates increased from 4.8% to 34.4% when the centre of lag
      screw was not in the second quarter of the head-neck interface line (the so
      called "safe zone") (p=0.001). Lag screw insertion lower or higher than 11 mm of
      the head apex line were associated with failure rates of 5.5% and 18.6%,
      respectively (p=0.004). Multivariate logistic regression showed that lag screw
      insertion not within the "safe-zone" was associated an Odds Ratio of 13.4 (95% CI
      2.24-81) for mechanical failure (p=0.004). CONCLUSIONS: The TAD scale focuses on
      length measurement and lacks the vector properties of multidirectional
      measurements. Vector analysis revealed that the caudal-cranial correct lag screw
      position is the most important factor in preventing mechanical failure.

PMID- 22134115
TI  - Electrophysiological insights into processing nonverbal emotional vocalizations.
AB  - The ability to identify emotions from the human voice is a crucial aspect of
      social cognition. Currently, very little is known about the neural correlates of
      nonverbal emotional vocalizations processing. We used electrophysiological
      measures to examine the processing of emotional versus neutral vocalizations.
      Participants listened to nonverbal angry, happy, and neutral vocalizations, as
      well as to monkey voices, which served as a response target. Angry sounds were
      processed differently than happy and neutral ones starting at 50 ms, whereas both
      vocal emotions were associated with decreased N100 and increased P200 components
      relative to neutral sounds. These findings indicate a rapid and automatic
      differentiation of emotional as compared with neutral vocalizations and suggest
      that this differentiation is not dependent on valence.

PMID- 22134116
TI  - Therapeutic efficacy of a lipid-based prodrug of mitomycin C in pegylated
      liposomes: studies with human gastro-entero-pancreatic ectopic tumor models.
AB  - BACKGROUND: A mitomycin-C lipid-based prodrug (MLP) formulated in pegylated
      liposomes (PL-MLP) was previously reported to have significant antitumor activity
      and reduced toxicity in mouse tumor models (Clin Cancer Res 12:1913-20, 2006).
      MLP is activated by thiolysis releasing mitomycin-C (MMC) which rapidly
      dissociates from liposomes. The purpose of this study was to examine the plasma
      stability, pharmacokinetics, and antitumor activity of PL-MLP in mouse models of
      human gastroentero-pancreatic tumors. METHODS: MLP was incorporated with almost
      100% efficiency in pegylated liposomes composed of hydrogenated
      phosphatidylcholine, with or without cholesterol (Chol). Mean vesicle size was 45
      65 nm for liposome preparations downsized by homogenization, and 80-100 nm when
      downsized by extrusion, the latter displaying narrower polydispersity. MLP to
      phospholipid mole ratio was 5% (~20 MUg MMC-equivalents/MUmol). Therapeutic
      studies were carried out in the N87 gastric carcinoma (Ca), HCT15 colon Ca, and
      Panc-1 pancreatic Ca models implanted s.c. in CD1 nude mice. Treatment was
      administered i.v. in mice with established tumors. RESULTS: PL-MLP was very
      stable when incubated in plasma, and whole blood with a maximum of 5% release and
      activation to free MMC after 24 h. In the presence of a strong reducing agent
      (dithiotreitol), MLP was almost entirely activated to free MMC. Pharmacokinetic
      studies revealed major differences in plasma clearance between free MMC and PL
      MLP. The longest half-lives were observed for extruded and Chol-containing
      preparations. Using a liposome radiolabel, it was found that the plasma levels of
      liposomes and prodrug were nearly superimposable confirming the absence of drug
      leakage in circulation. In vivo prodrug activation was significantly increased by
      co-injection of a large dose of a biocompatible reducing agent, N-acetylcysteine.
      PL-MLP was significantly more effective in delaying tumor growth and resulted in
      more tumor regressions than irinotecan in the N87 and HCT15 models, and than
      gemcitabine in the Panc-1 model. PL-MLP was ~3-fold less toxic than free MMC at
      MMC-equivalent doses, and displayed mild myelosuppression at therapeutic doses.
      CONCLUSIONS: Delivery of MLP in pegylated liposomes is more effective than
      conventional chemotherapy in the treatment of gastroentero-pancreatic ectopic
      tumor models, and may represent an effective tool for treatment of these
      malignancies in the clinical setting with improved safety over free MMC. Reducing
      agents offer a tool for controlling in vivo prodrug release.

PMID- 22134119
TI  - Culture of human corneal endothelial cells isolated from corneas with Fuchs
      endothelial corneal dystrophy.
AB  - The purpose of this study was to assess the feasibility of initiating primary
      cultures of corneal endothelial cells from patients suffering from Fuchs
      endothelial corneal dystrophy (FECD; MIM# 1036800). We also evaluated which
      conditions yielded the best results for culture. Twenty-nine patients undergoing
      Descemet stripping automated endothelial keratoplasty consented to the use of
      their excised Descemet's membrane for this study. Out of the 29 specimens, 18
      successfully initiated a culture. Cell morphology varied between endothelial
      (rounded, slightly elongated cells, n = 12) and fibroblastic-like (thin and very
      elongated cells, n = 6). These differences in cell morphology were also observed
      with the normal human corneal endothelial cell cultures. The cultures that
      initially presented an endothelial morphology maintained their shape in
      subcultures. Clusterin expression was similar in FECD and normal endothelial
      cells. Transmission electron microscopy of FECD Descemet's membranes showed a
      high degree of various abnormalities generally found in this disease, such as a
      thickened Descemet's membrane, presence of a posterior banded layer, presence of
      a fibrillar layer and striated bodies of various sizes and periodicities.
      Patient's age was predictive of culture success, all younger FECD donors
      generating cultures of endothelial morphology. The absence of a fibrillar layer
      was also a factor associated with greater success. Culture success was not
      dependent on specimen size, specimen pigmentation, or patient's preoperative
      central corneal thickness. In conclusion, this paper shows for the first time
      that central Descemet's membranes of patients suffering from FECD possess
      proliferative endothelial cells that can be isolated and cultured without viral
      transduction, opening the way for new in vitro studies of this disease.

PMID- 22134120
TI  - The presence of the -866A/55Val/Ins haplotype in the uncoupling protein 2 (UCP2)
      gene is associated with decreased UCP2 gene expression in human retina.
AB  - Uncoupling protein 2 (UCP2) is a mitochondrial transporter present in the inner
      membrane of mitochondria, and it uncouples substrate oxidation from ATP
      synthesis, thereby dissipating the membrane potential energy and consequently
      decreasing ATP production by mitochondrial respiratory chain. As a consequence of
      the uncoupling, UCP2 decreases the reactive oxygen species (ROS) formation by
      mitochondria. ROS overproduction is related to diabetic retinopathy (DR), a
      chronic complication of diabetes mellitus (DM). Recently, our group reported that
      the -866A/55Val/Ins haplotype (-866G/A, Ala55Val and Ins/Del polymorphisms) of
      the UCP2 gene was associated with increased risk for DR in patients with DM. The
      purpose of this study was to analyze the effect of this haplotype on UCP2 gene
      expression in human retina. In addition, MnSOD2 gene expression was also
      investigated according to different UCP2 haplotypes. This cross-sectional study
      included 188 cadaveric cornea donors. In a subset of 91 retinal samples
      differentiated according to the presence of the mutated UCP2 haplotype and risk
      alleles of the -866G/A and Ins/Del polymorphisms, UCP2 and MnSOD2 gene
      expressions were measured by semi-quantitative RT-qPCR. Mutated UCP2 haplotype
      carriers (homozygous + heterozygous) had a lower UCP2 gene expression than
      reference haplotype carriers (8.4 +/- 7.6 vs. 18.8 +/- 23.7 arbitrary units; P =
      0.046). Accordingly, UCP2 gene expression was decreased in -866A carriers when
      compared with G/G carriers (P = 0.010). UCP2 gene expression did not differ
      between Ins allele carriers and Del/Del carriers (P = 0.556). Interestingly,
      subjects carrying the heterozygous UCP2 haplotype showed increased MnSOD2 gene
      expression (P = 0.025). This is the first report suggesting that the presence of
      the -866A/55Val/Ins haplotype is associated with decreased UCP2 gene expression
      in human retina. Possibly, MnSOD2 expression might influence the UCP2 effect in
      the protection against oxidative stress.

PMID- 22134117
TI  - Effect of oleic acid modified polymeric bilayered nanoparticles on percutaneous
      delivery of spantide II and ketoprofen.
AB  - The objective of the present study was to evaluate the effect of oleic acid
      modified polymeric bilayered nanoparticles (NPS) on combined delivery of two anti
      inflammatory drugs, spantide II (SP) and ketoprofen (KP) on the skin permeation.
      NPS were prepared using poly(lactic-co-glycolic acid) (PLGA) and chitosan. SP and
      KP were encapsulated in different layers alone or/and in combination (KP-NPS, SP
      NPS and SP+KP-NPS). The surface of NPS was modified with oleic acid (OA)
      ('Nanoease' technology) using an established procedure in the laboratory (KP-NPS
      OA, SP-NPS-OA and SP+KP-NPS-OA). Fluorescent dyes (DiO and DID) containing
      surface modified (DiO-NPS-OA and DID-NPS-OA) and unmodified NPS (DiO-NPS and DID
      NPS) were visualized in lateral rat skin sections using confocal microscopy and
      Raman confocal spectroscopy after skin permeation. In vitro skin permeation was
      performed in dermatomed human skin and HPLC was used to analyze the drug levels
      in different skin layers. Further, allergic contact dermatitis (ACD) model was
      used to evaluate the response of KP-NPS, SP-NPS, SP+KP-NPS, KP-NPS-OA, SP-NPS-OA
      and SP+KP-NPS-OA treatment in C57BL/6 mice. The fluorescence from OA modified NPS
      was observed up to a depth of 240MUm and was significantly higher as compared to
      non-modified NPS. The amount of SP and KP retained in skin layers from OA
      modified NPS increased by several folds compared to unmodified NPS and control
      solution. In addition, the combination index value calculated from ACD response
      for solution suggested an additive effect and moderate synergism for NPS-OA. Our
      results strongly suggest that surface modification of bilayered nanoparticles
      with oleic acid improved drug delivery to the deeper skin layers.

PMID- 22134121
TI  - Surgical outcome of robotic surgery in morbidly obese patient with endometrial
      cancer compared to laparotomy.
AB  - INTRODUCTION: Before the introduction of robotic surgery at our institution, most
      obese women of class 2 or greater (body mass index [BMI] >35) underwent a
      laparotomy for the management of endometrial cancer. Since November 2008, we have
      performed most of these cases in a robotic fashion. This manuscript presents the
      outcome of these women in comparison with a historical cohort of women treated
      with laparotomy. METHODS: Women with clinical stage I or II endometrial cancer
      and a BMI greater than 35 kg/m treated with robotic surgery at our institution
      between November 2008 and November 2010 were compared with a historical cohort of
      similar patients who underwent laparotomy. Patients' characteristics, operating
      room time, type of surgery, length of hospital stay, and incidence of
      perioperative complications were compared between the 2 groups. RESULTS: A total
      of 86 women were analyzed in this study (robotic surgery, 45; laparotomy, 41).
      The overall intraoperative complication rate is 5.8%. There is no statistical
      difference in age, number of comorbidities, BMI, prior abdominal surgery, and
      operative complications between the women who underwent robotic surgery versus
      laparotomy. Postoperative complication rates are higher in the laparotomy group
      (44% vs 17.7%; P = 0.007), and hospital length of stay is also higher in the
      laparotomy group (4 vs 2 days; P < 0.001). There is no difference in rates of
      (pelvic) lymph node dissection; however, para-aortic node dissection is more
      common in the robotic surgery group. CONCLUSION: Robotic surgery for the surgical
      management of the morbidly obese patient is shown to be safe and have less
      perioperative complications compared with open surgery.

PMID- 22134122
TI  - Target screening and confirmation of 35 licit and illicit drugs and metabolites
      in hair by LC-MSMS.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MSMS) target screening in
      50mg hair was developed and fully validated for 35 analytes (Delta9
      tetrahidrocannabinol (THC), morphine, 6-acetylmorphine, codeine, methadone,
      fentanyl, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4
      methylenedioxymethamphetamine, benzoylecgonine, cocaine, lysergic acid
      diethylamide, ketamine, scopolamine, alprazolam, bromazepam, clonazepam,
      diazepam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, lormetazepam,
      nordiazepam, oxazepam, tetrazepam, triazolam, zolpidem, zopiclone, amitriptyline,
      citalopram, clomipramine, fluoxetine, paroxetine and venlafaxine). Hair
      decontamination was performed with dichloromethane, and incubation in 2 mL of
      acetonitrile at 50 degrees C overnight. Extraction procedure was performed in 2
      steps, first liquid-liquid extraction, hexane:ethyl acetate (55:45, v:v) at pH 9,
      followed by solid-phase extraction (Strata-X cartridges). Chromatographic
      separation was performed in AtlantisT3 (2.1 mm * 100 mm, 3 MUm) column,
      acetonitrile and ammonium formate pH 3 as mobile phase, and 32 min total run
      time. One transition per analyte was monitored in MRM mode. To confirm a positive
      result, a second injection monitoring 2 transitions was performed. The method was
      specific (no endogenous interferences, n=9); LOD was 0.2-50 pg/mg and LOQ 0.5-100
      pg/mg; linearity ranged from 0.5-100 to 2000-20,000 pg/mg; imprecision <15%;
      analytical recovery 85-115%; extraction efficiency 4.1-85.6%; and process
      efficiency 2.5-207.7%; 27 analytes showed ion suppression (up to -86.2%), 4 ion
      enhancement (up to 647.1%), and 4 no matrix effect; compounds showed good
      stability 24-48 h in autosampler. The method was applied to 17 forensic cases. In
      conclusion, a sensitive and specific target screening of 35 analytes in 50mg
      hair, including drugs of abuse (THC, cocaine, opiates, amphetamines) and
      medicines (benzodiazepines, antidepressants) was developed and validated,
      achieving lower cut-offs than Society of Hair Testing recommendations.

PMID- 22134123
TI  - Attenuation of CCl(4)-induced hepatic oxidative stress in rat by Launaea
      procumbens.
AB  - Antioxidant effects of Launaea procumbens methanol extract (LPME) were evaluated
      against CCl(4)-induced oxidative stress in liver of rat. 48 male rats were
      equally divided in to 8 groups (06 rats each). Group I (control) remained
      untreated, while Group II was given vehicles (olive oil and DMSO). Animals of
      Groups III, IV, V, VI and VII were injected intraperitoneally with CCl(4) (3
      ml/kg b.w.; i.p., 20% CCl(4)/olive oil) twice a week for four weeks. Group III
      received only CCl(4) while Group IV was given rutin (50 mg/kg b.w.). Group V, VI
      and VII were administered LPME at a dose of 100, 150 and 200 mg/kg b.w.,
      respectively. Animals of Group VIII received LPME (200 mg/kg b.w.) alone.
      Oxidative stress induced with CCl(4) in liver was evident by a significant
      increase in triglycerides, total cholesterol, LDL-cholesterol, and enzymatic
      activities of AST, ALT, ALP, LDH, gamma-GT activities in serum. Level of lipid
      peroxidation, nitrite, and hydrogen peroxide concentration, DNA injuries in liver
      samples was also increased with CCl(4). GSH concentration in liver was
      significantly decreased, as were the activities of antioxidant enzymes; CAT, POD,
      SOD, GSH-Px, GST, GSR, QR. Co-treatment of rats with LPME and rutin prevented all
      the changes observed with CCl(4). Hepatic lesions and telomerase activity induced
      with CCl(4) was also suppressed with LPME and rutin. It is suggested that LPME
      effectively prevented the CCl(4)-induced oxidative injuries in liver, possibly
      through antioxidant and/or free radical scavenging effects of flavonoids and
      phenolic compounds in the extract.

PMID- 22134124
TI  - Short and scalable synthesis of an anhydride precursor of the environment
      sensitive fluorophore 6-dimethylaminonaphthalimide.
AB  - Environment-sensitive fluorophores have different quantum yields in different
      solvents. 6-Dimethylaminonaphthalimide (6-DMN), for example, has a low quantum
      yield in aqueous solutions, but is highly fluorescent in nonpolar solvents or
      when bound to hydrophobic sites in proteins or membranes. 6-DMN has been used to
      investigate protein-protein interactions, as well as the in-tissue distribution
      and internalization of delta-receptors. This protocol describes a highly
      efficient three-stage synthesis of 6-dimethylamino-2,3-naphthalenedicarboxylic
      anhydride (compound 1), which is a stable precursor that can be converted to 6
      DMN. The three stages are (i) photo-bromination of 4-nitro-o-xylene (yield 82%),
      (ii) Diels-Alder reaction followed by base hydrolysis, resulting in 6-nitro-2,3
      naphthalenedicarboxylic acid (yield 87%) and (iii) reductive amination followed
      by dehydration (yield 76.5%) to form compound 1. The synthesis can be performed
      on a gram scale (in 55 h over 3 d) with an overall yield of about 55%. It can
      easily be modified to prepare related compounds by, for example, performing
      different reactions using 6-nitro-2,3-naphthalenedicarboxylic acid.

PMID- 22134125
TI  - Transposon-mediated BAC transgenesis in zebrafish.
AB  - Bacterial artificial chromosomes (BACs) are widely used in studies of vertebrate
      gene regulation and function because they often closely recapitulate the
      expression patterns of endogenous genes. Here we report a step-by-step protocol
      for efficient BAC transgenesis in zebrafish using the medaka Tol2 transposon.
      Using recombineering in Escherichia coli, we introduce the iTol2 cassette in the
      BAC plasmid backbone, which contains the inverted minimal cis-sequences required
      for Tol2 transposition, and a reporter gene to replace a target locus in the BAC.
      Microinjection of the Tol2-BAC and a codon-optimized transposase mRNA into
      fertilized eggs results in clean integrations in the genome and transmission to
      the germline at a rate of ~15%. A single person can prepare a dozen constructs
      within 3 weeks, and obtain transgenic fish within approximately 3-4 months. Our
      protocol drastically reduces the labor involved in BAC transgenesis and will
      greatly facilitate biological and biomedical studies in model vertebrates.

PMID- 22134126
TI  - Design and self-assembly of siRNA-functionalized RNA nanoparticles for use in
      automated nanomedicine.
AB  - Individual genes can be targeted with siRNAs. The use of nucleic acid
      nanoparticles (NPs) is a convenient method for delivering combinations of
      specific siRNAs in an organized and programmable manner. We present three
      assembly protocols to produce two different types of RNA self-assembling
      functional NPs using processes that are fully automatable. These NPs are
      engineered based on two complementary nanoscaffold designs (nanoring and
      nanocube), which serve as carriers of multiple siRNAs. The NPs are functionalized
      by the extension of up to six scaffold strands with siRNA duplexes. The assembly
      protocols yield functionalized RNA NPs, and we show that they interact in vitro
      with human recombinant Dicer to produce siRNAs. Our design strategies allow for
      fast, economical and easily controlled production of endotoxin-free therapeutic
      RNA NPs that are suitable for preclinical development.

PMID- 22134127
TI  - Use of target protector morpholinos to analyze the physiological roles of
      specific miRNA-mRNA pairs in vivo.
AB  - MicroRNAs (miRNAs) regulate gene expression by pairing with complementary
      sequences in the 3' untranslated regions (UTRs) of transcripts. Although the
      molecular mechanism underlying miRNA biogenesis and activity is becoming better
      understood, determining the physiological role of the interaction of an miRNA
      with its target remains a challenge. A number of methods have been developed to
      inhibit individual miRNAs, but it can be difficult to determine which specific
      targets are responsible for any observed phenotypes. To address this problem, we
      use target protector (TP) morpholinos that interfere with a single miRNA-mRNA
      pair by binding specifically to the miRNA target sequence in the 3' UTR. In this
      protocol, we detail the steps for identifying miRNA targets, validating their
      regulation and using TPs to interrogate their function in zebrafish. Depending on
      the biological context, this set of experiments can be completed in 6-8 weeks.

PMID- 22134128
TI  - Analysis of RhoA and Rho GEF activity in whole cells and the cell nucleus.
AB  - We have recently shown that a fraction of the total cellular pool of the small
      GTPase RhoA resides in the nucleus, and that the nuclear guanine nucleotide
      exchange factor (GEF) Net1 has a role in the regulation of its activity. In this
      protocol, we describe a method to measure both the activities of the nuclear
      pools of RhoA and Rho GEFs. This process required the development of a nuclear
      isolation protocol that is both fast and virtually free of cytosolic and membrane
      contaminants, as well as a redesign of existing RhoA and Rho GEF activity assays
      so that they work in nuclear samples. This protocol can be also used for other
      Rho GTPases and Rho GEFs, which have also been found in the nucleus. Completion
      of the procedure, including nuclear isolation and RhoA or Rho GEF activity assay,
      takes 1 h 40 min. We also include details of how to perform a basic assay of
      whole-cell extracts.

PMID- 22134129
TI  - Propositional density and apolipoprotein E genotype among persons at risk for
      familial Alzheimer's disease.
AB  - BACKGROUND/AIMS: A relationship between decreased propositional density (p
      density) in young adulthood and future risk for Alzheimer's disease (AD) has been
      postulated, but multiple interpretations of the nature of this relationship are
      possible. This study explored the relationship between familial AD (FAD) mutation
      status, apolipoprotein E (APOE) genotype, and p-density. METHODS: Thirty-five non
      demented persons at risk for FAD mutations were recruited. Subjects wrote brief
      biographical essays from which p-density, the ratio of the number of unique ideas
      to the number of words in the text, was calculated. mixed-effects regression
      models were used to examine the relationship of p-density and fad mutation status
      and apoe genotype. RESULTS: FAD mutation status was not significantly associated
      with p-density. However, results from both models indicated that the presence of
      the APOE epsilon4 allele was significantly associated with p-density (p <
      0.0001), with APOE epsilon4 carriers having lower p-density than non-carriers.
      CONCLUSIONS: Our results are consistent with an influence of APOE status on p
      density in young adulthood that is independent of the AD risk per se and suggest
      the previous finding of increased risk for the development of AD in persons with
      decreased p-density may be related to APOE genotype.

PMID- 22134130
TI  - Primary erythromelalgia with severe ulcers and successful ulcer treatment with
      sorbalgon.

PMID- 22134131
TI  - Supramolecular polymorphism of the 1:1 molecular salt (adamantane-1-carboxylate
      3,5,7-tricarboxylic acid).(hexamethylenetetraminium). A "failed" crystal
      engineering attempt.
AB  - The tetrahedral arrangement of hydrogen bonding donor and acceptor groups is used
      to rationalise the design of a diamondoid network; however, a single proton
      transfer renders the four sites inequivalent, and results in two polymorphs of
      the title molecular salt utilizing similar intermolecular synthons.

PMID- 22134132
TI  - Comparison of pharmacokinetics, pharmacodynamics, safety, and tolerability of the
      amyloid beta monoclonal antibody solanezumab in Japanese and white patients with
      mild to moderate alzheimer disease.
AB  - OBJECTIVES: Solanezumab is a humanized anti-amyloid beta monoclonal antibody
      being developed as a passive immunization treatment to slow the progression of
      Alzheimer disease (AD). Pharmacokinetics (PK), pharmacodynamics, safety, and
      tolerability after a single dose of solanezumab were compared between Japanese
      and white patients with AD. METHODS: Japanese and white patients with mild to
      moderate AD were enrolled in 2 separate studies. In each study, single doses of
      solanezumab at 0.5, 1.5, 4.0, and 10.0 mg/kg were administered by intravenous
      infusion. Plasma concentrations of solanezumab and amyloid beta (Abeta) were
      measured. A safety assessment was conducted up to 112 days after a single-dose
      administration of solanezumab. RESULTS: The PK profile was similar between the
      Japanese and the white patients with AD. In both the Japanese and the white
      patients, clearance and volume of distribution appeared similar across doses,
      suggesting that solanezumab exhibited dose-proportional PK within the studied
      dose range. A marked increase in plasma total Abeta was observed; both the
      magnitude and time to reach maximum concentration tended to increase with
      increasing doses of solanezumab. Administration of solanezumab was generally well
      tolerated in both Japanese and white patients with AD. CONCLUSIONS: When
      administered as a per-kilogram single dose of solanezumab, PK and
      pharmacodynamics (plasma total Abeta1-40 concentration) in the Japanese patients
      with AD were comparable with those in the white patients with AD. In addition,
      solanezumab was generally well tolerated in both Japanese and white patients at
      all dose levels.

PMID- 22134133
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses spheroids attachment on
      endometrial epithelial cells through the down-regulation of the Wnt-signaling
      pathway.
AB  - The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects
      embryo development, implantation and fertility in humans. The underlying
      molecular mechanism by which TCDD suppresses implantation remains largely
      unknown. We used the trophoblastic spheroids (embryo surrogate)-endometrial cells
      co-culture assay to study the attachment of trophoblastic spheroids (BeWo and Jeg
      3) onto the endometrial epithelial (RL95-2 and Ishikawa) cells. TCDD dose
      dependently induced cytochrome P450 1A1 (Cyp1A1) expression in trophoblastic and
      endometrial epithelial cells. Moreover, TCDD at 1 and 10 nM suppressed beta
      catenin (a Wnt-signaling molecule) and E-cadherin expression, as well as
      spheroids attachment onto endometrial cells. Interestingly, activation of the
      canonical Wnt-signaling pathway via Wnt3a or lithium chloride reverted the
      suppressive effect of TCDD on beta-catenin and E-cadherin expressions in the BeWo
      and RL95-2 cells, and restored the spheroids attachment rate to be comparable to
      the untreated controls. Taken together, TCDD induces Cyp1A1 expression, modulates
      the Wnt-signaling pathway and suppresses spheroids attachment onto endometrial
      cells.

PMID- 22134134
TI  - Apixaban and rivaroxaban safety after hip and knee arthroplasty: a meta-analysis.
AB  - Direct experimental safety comparisons of Xa coagulation factor direct
      inhibitors, apixaban and rivaroxaban, on their approved therapeutic indications
      have not been identified. Due to recently raised safety concerns, a meta-analysis
      was carried out pooling data from studies identified on a Medline and Cochrane
      Library search in order to better evaluate the safety profile of both drugs.
      Abstracts from scientific meetings were also searched from 2003 to 2011. Primary
      and secondary outcome measures were major bleeding and total bleeding,
      respectively. Relative risks (RRs) were estimated using random effects models and
      statistical heterogeneity was estimated with I(2) statistics. Of the 160 screened
      publications, 12 clinical trials were included in which enoxaparin was the active
      control. For knee arthroplasty, apixaban was associated with significantly fewer
      major bleeding events (6496 patients, RR 0.56, 95% confidence interval [CI] 0.32
      0.96) and fewer total bleeding events (6496 patients, RR 0.81, 95% CI 0.67-0.97).
      There were no significant differences in the incidence of major bleeding events
      (5699 patients, RR 1.40, 95% CI 0.56-3.52) or in the incidence of total bleeding
      events for rivaroxaban (5699 patients, RR 1.09, 95% CI 0.91-1.30). No differences
      were found when thromboprophylaxis after hip replacement was the case. Apixaban
      seems to be associated with a lower risk of the incidence of hemorrhagic events
      after total knee arthroplasty. For hip arthroplasty, no differences were found
      between the studied drugs.

PMID- 22134135
TI  - Nontoxic medical imaging agents form toxic DBPs.

PMID- 22134136
TI  - The Jab1-E2F1 interaction: a matter of life and death.

PMID- 22134137
TI  - Expanding NFkappaB and SUMO ties.

PMID- 22134139
TI  - 4G/5G Polymorphism of the plasminogen activator inhibitor-1 gene is associated
      with multiple organ dysfunction in critically ill patients.
AB  - OBJECTIVE: Impaired fibrinolysis is associated with a higher incidence of both
      multiple organ dysfunction and mortality in the intensive care unit (ICU).
      Plasminogen activator inhibitor (PAI)-1 is the chief inhibitor of fibrinolysis.
      We investigated the influence of the 4G/5G polymorphism (rs1799768) of the PAI-1
      gene on the plasma PAI-1 level and the outcome of critically ill patients.
      METHODS: In 41 consecutive patients admitted to the ICU, PAI-1 gene polymorphism
      was assessed, plasma PAI-1 and arterial lactate concentrations were measured and
      clinical severity scores were recorded. RESULTS: Homozygotes for the 4G allele
      had higher plasma levels of PAI-1 antigen. The mean +/- SD PAI-1 antigen level
      was 193.31 +/- 167.93 ng/ml for the 4G/4G genotype, 100.67 +/- 114.16 ng/ml for
      the 4G/5G genotype and 0.43 +/- 0.53 ng/ml for the 5G/5G genotype. There was a
      significant correlation between plasma PAI-1 and arterial lactate concentrations,
      as well as between PAI-1 and severity scores. The mortality rate was 63, 33 and
      0% for patients with the 4G/4G, 4G/5G and 5G/5G genotypes, respectively.
      CONCLUSIONS: These results demonstrate that the 4G/5G polymorphism of the PAI-1
      gene affects the plasma PAI-1 concentration, which could impair fibrinolysis and
      cause organ failure, and thus the presence of the 4G allele increases the risk of
      death.

PMID- 22134138
TI  - Artemis interacts with the Cul4A-DDB1DDB2 ubiquitin E3 ligase and regulates
      degradation of the CDK inhibitor p27.
AB  - Artemis, a member of the SNM1 gene family, is a multifunctional phospho-protein
      that has been shown to have important roles in V(D)J recombination, DNA double
      strand break repair, and stress-induced cell-cycle checkpoint regulation. We show
      here that Artemis interacts with the Cul4A-DDB1 E3 ubiquitin ligase via a direct
      interaction with the substrate-specificity receptor DDB2. Furthermore, Artemis
      also interacts with the CDK inhibitor and tumor suppressor p27, a substrate of
      the Cul4A-DDB1 ligase, and both DDB2 and Artemis are required for the degradation
      of p27 mediated by this complex. We also show that the regulation of p27 by
      Artemis and DDB2 is important for cell cycle progression in normally
      proliferating cells and in response to serum deprivation. These findings thus
      define a function for Artemis as an effector of Cullin-based E3 ligase-mediated
      ubiquitylation, demonstrate a novel pathway for the regulation of p27, and show
      that Cul4A-DDB1(DDB2-Artemis) regulates G1 phase cell cycle progression in
      mammalian cells.

PMID- 22134140
TI  - Outcome predictors in guided and unguided self-help for social anxiety disorder.
AB  - Internet-based self-help with therapist guidance has shown promise as an
      effective treatment and may increase access to evidence-based psychological
      treatment for social anxiety disorder (SAD). Although unguided self-help has been
      suggested primarily as a population-based preventive intervention, some studies
      indicate that patients with SAD may profit from unguided self-help. Gaining
      knowledge about predictors of outcome in guided and unguided self-help for SAD is
      important to ensure that these interventions can be offered to those who are most
      likely to respond. Utilizing a sample of 245 patients who received either guided
      or unguided self-help for SAD, the present study examined pre-treatment symptoms
      and program factors as predictors of treatment adherence and outcome. The results
      were in line with previous findings from the face-to-face treatment literature:
      namely, the intensity of baseline SAD symptoms, but not depressive symptoms,
      predicted treatment outcomes in both unguided and guided self-help groups.
      Outcomes were unrelated to whether a participant has generalized versus specific
      SAD. Furthermore, for the unguided self-help group, higher credibility ratings of
      the treatment program were associated with increased treatment adherence. The
      findings suggest that guided and unguided self-help may increase access to SAD
      treatment in a population that is more heterogeneous than previously assumed.

PMID- 22134141
TI  - Complete regression of an atypical fibroxanthoma.

PMID- 22134142
TI  - The relationship between intracranial pressure and brain oxygenation in children
      with severe traumatic brain injury.
AB  - BACKGROUND: Intracranial pressure (ICP) monitoring is a cornerstone of care for
      severe traumatic brain injury (TBI). Management of ICP can help ensure adequate
      cerebral blood flow and oxygenation. However, studies indicate that brain hypoxia
      may occur despite normal ICP and the relationship between ICP and brain
      oxygenation is poorly defined. This is particularly important for children in
      whom less is known about intracranial dynamics. OBJECTIVE: To examine the
      relationship between ICP and partial pressure of brain tissue oxygen (PbtO2) in
      children with severe TBI (Glasgow Coma Scale score <= 8) admitted to Red Cross
      War Memorial Children's Hospital, Cape Town. METHODS: The relationship between
      time-linked hourly and high-frequency ICP and PbtO2 data was examined using
      correlation, regression, and generalized estimating equations. Thresholds for ICP
      were examined against reduced PbtO2 using age bands and receiver-operating
      characteristic curves. RESULTS: Analysis using more than 8300 hourly (n = 75) and
      1 million high-frequency data points (n = 30) demonstrated a weak relationship
      between ICP and PbtO2 (r = 0.05 and r = 0.04, respectively). No critical ICP
      threshold for low PbtO2 was identified. Individual patients revealed a strong
      relationship between ICP and PbtO2 at specific times, but different relationships
      were evident over longer periods. CONCLUSION: The relationship between ICP and
      PbtO2 appears complex, and several factors likely influence both variables
      separately and in combination. Although very high ICP is associated with reduced
      PbtO2, in general, absolute ICP has a poor relationship with PbtO2. Because
      reduced PbtO2 is independently associated with poor outcome, a better
      understanding of ICP and PbtO2 management in pediatric TBI seems to be needed.

PMID- 22134143
TI  - The epistasis between vascular homeostasis genes is apparent in essential
      hypertension.
AB  - OBJECTIVE: The epistasis influence of vascular homeostasis genes is vital to
      multigenetic diseases. This study was designed to perceive the possible role of
      epistasis in the etiology of essential hypertension. METHODS: We investigated
      seven polymorphisms of ACE, CYP11B2 and NOS3 epistatically, and SBP, DBP, MAP,
      ACE activity, plasma aldosterone concentration (PAC) and NOx level in 860 age-
      and ethnicity-matched unrelated north-Indian subjects. RESULTS: The hypertension
      risk in individuals with interacted-genotypes (IwIw+IwIc)+(4aa), (IcIc)+(4bb+4ba)
      and IcIc+4aa of the CYP11B2 and NOS3 was significantly higher with odds ratio 5.5
      (95% CI=2.9-10.6, P<0.0001), 2.4 (95% CI=1.4-4.1, P<0.0008) and 7.5 (95% CI=1.6
      34.8, P=0.010), respectively. The odds ratio for hypertension with interacted
      haplotypes (-344T/Ic)+(-922A/-786T/4a/894G) and (-344T/Ic)+(-922G/-786C/4a/894G)
      of CYP11B2 and NOS3 was 5.3 (95% CI=2.0-14.2, P=0.005) and 3.9 (95% CI=1.4-10.4,
      P=0.04), respectively; whereas for the protective interacted-haplotypes (
      344T/Iw)+(-922A/-786T/4b/894G), the odds ratio was 0.7 (95% CI=0.5-0.9, P=0.03).
      While the interacted-genotypes, IcIc+4aa correlated with higher SBP and MAP
      (P=0.006; P=0.04), the interacted-haplotypes, (-344T/Ic)+(-922A/-786T/4a/894G)
      and (-344T/Ic)+(-922G/-786C/4a/894G) correlated with higher MAP and lower NOx
      level (P=0.02 and P=0.03, respectively), and the protective interacted-haplotypes
      (-344T/Iw)+(-922A/-786T/4b/894G) correlated with lower PAC and MAP (P=0.024 and
      P=0.018, respectively). CONCLUSIONS: The epistasis between CYP11B2 and NOS3 and
      its correlation with varied clinical and biochemical parameters signify its
      possible contribution in the complex etiology of hypertension.

PMID- 22134144
TI  - Similar mortality and reduced loss to follow-up in integrated compared with
      vertical programs providing antiretroviral treatment in sub-saharan Africa.
AB  - BACKGROUND: Vertical HIV programs have achieved good results but may not be
      feasible or appropriate in many resource-limited settings. Medecins sans
      Frontieres has treated HIV in vertical programs since 2000 and over time
      integrated HIV treatment into general health care services using simplified
      protocols. We analyzed the survival probability among patients receiving
      antiretroviral therapy (ART) from 2003 to 2010 in integrated versus vertical
      programs in 9 countries in sub-Saharan Africa. METHODS AND FINDINGS: Cox
      regression assessed mortality and program design association, adjusting for
      baseline age, body mass index, clinical WHO stage, tuberculosis, program age and
      setting. The analysis included 15,403 HIV-positive adults on ART in 7 vertical
      (14,124 patients) and 10 integrated (1279 patients) programs. Cox regression
      including 14,523 patients followed for up to 30 months ART showed similar
      outcomes for mortality (adjusted hazard ratio (aHR) 1.02; 95% confidence interval
      (CI): 0.83 to 1.24) and lower risk of loss to follow-up (aHR: 0.71; 95% CI: 0.61
      to 0.83) in integrated compared with vertical programs. The greatest risk of
      death was from initiating ART at WHO stage 4 (aHR 1.99, 95% CI: 1.74 to 2.29),
      although greater program experience was protective (aHR: 0.77, 95% CI: 0.66 to
      0.89). Risk of loss to follow-up was greater in experienced programs (aHR: 3.33;
      95% CI: 2.92 to 3.79) and rural settings (aHR: 3.82; 95% CI: 3.49 to 4.20).
      CONCLUSIONS: ART delivery in integrated general health care programs results in
      good outcomes. Compared with vertical HIV programs, patients initiated ART in
      integrated programs at more advanced stages of clinical immunosuppression yet had
      similar risk of death and lower risk of loss to follow-up.

PMID- 22134145
TI  - Intrapartum single-dose carbamazepine reduces nevirapine levels faster and may
      decrease resistance after a single dose of nevirapine for perinatal HIV
      prevention.
AB  - BACKGROUND: World Health Organization guidelines recommend zidovudine +
      lamivudine for 7 days from labor onset in HIV-infected women receiving single
      dose nevirapine (sdNVP) to cover prolonged subtherapeutic nevirapine
      concentrations. Although effective, this is complicated and does not eliminate
      resistance; alternative strategies could add benefit. METHODS: Antiretroviral
      naive HIV-infected pregnant women aged 18-40 years, with CD4 >200 cells per cubic
      millimeter, able to regularly attend the antenatal clinics in Moshi, Tanzania,
      were enrolled 1:1 by alternate allocation to receive 200 mg sdNVP alone or in
      combination with open-label 400-mg single-dose carbamazepine (sdNVP/CBZ) at
      delivery (ClinicalTrials.gov NCT00294892). The coprimary outcomes were nevirapine
      plasma concentrations 1 week and nevirapine resistance mutations 6 weeks
      postpartum. Analyses were based on those still eligible at delivery. RESULTS:
      Ninety-seven women were assigned to sdNVP and 95 to sdNVP/CBZ during pregnancy,
      of whom 75 sdNVP and 83 sdNVP/CBZ were still eligible at delivery at study sites.
      The median (interquartile range) nevirapine plasma concentration was 1.55 (0.88
      1.84) mg/L in sdNVP (n = 61) and 1.40 (0.93-1.97) mg/L in sdNVP/CBZ (n = 72) at
      delivery (P = 0.91), but 1 week later was significantly lower in sdNVP/CBZ [n =
      63; 0.09 (0.05-0.20) mg/L] than in sdNVP [n = 52; 0.20 (0.09-0.31) mg/L; rank
      sum: P = 0.004] (geometric mean ratio: 0.64, 95% confidence interval: 0.43 to
      0.96; P = 0.03). Six weeks postpartum, nevirapine mutations were observed in 11
      of 52 (21%) in sdNVP and 6 of 55 (11%) in sdNVP/CBZ (odds ratio = 0.46, 95%
      confidence interval: 0.16 to 1.34; P = 0.15). CONCLUSIONS: Addition of single
      dose carbamazepine to sdNVP at labor onset in HIV-infected, pregnant women did
      not affect nevirapine plasma concentration at delivery, but significantly reduced
      it 1 week postpartum, with a trend toward fewer nevirapine resistance mutations.

PMID- 22134146
TI  - Cervical cancer prevention in HIV-infected women using the "see and treat"
      approach in Botswana.
AB  - BACKGROUND: Cervical cancer is a major public health problem in resource-limited
      settings, particularly among HIV-infected women. Given the challenges of cytology
      based approaches, the efficiency of new screening programs need to be assessed.
      SETTING: Community and hospital-based clinics in Gaborone, Botswana. OBJECTIVE:
      To determine the feasibility and efficiency of the "see and treat" approach using
      visual inspection acetic acid (VIA) and enhanced digital imaging (EDI) for
      cervical cancer prevention in HIV-infected women. METHODS: A 2-tier community
      based cervical cancer prevention program was implemented. HIV-infected women were
      screened by nurses at the community using the VIA/EDI approach. Low-grade lesions
      were treated with cryotherapy on the same visit. Women with complex lesions were
      referred to our second tier specialized clinic for evaluation. Weekly quality
      control assessments were performed by a specialist in collaboration with the
      nurses on all pictures taken. RESULTS: From March 2009 through January 2011, 2175
      patients were screened for cervical cancer at our community-based clinic. Two
      hundred fifty-three patients (11.6%) were found to have low-grade lesions and
      received same-day cryotherapy. One thousand three hundred forty-seven (61.9%)
      women were considered to have a normal examination, and 575 (27.3%) were referred
      for further evaluation and treatment. Of the 1347 women initially considered to
      have normal exams, 267 (19.8%) were recalled based on weekly quality control
      assessments. Two hundred ten (78.6%) of the 267 recalled women, and 499 (86.8%)
      of the 575 referred women were seen at the referral clinic. Of these 709 women,
      506 (71.4%) required additional treatment. Overall, 264 cervical intraepithelial
      neoplasia stage 2 or 3 were identified and treated, and 6 microinvasive cancers
      identified were referred for further management. CONCLUSIONS: Our "see and treat"
      cervical cancer prevention program using the VIA/EDI approach is a feasible, high
      output and high-efficiency program, worthy of considering as an additional
      cervical cancer screening method in Botswana, especially for women with limited
      access to the current cytology-based screening services.

PMID- 22134150
TI  - Reconceptualizing research on HIV treatment outcomes among criminalized groups.

PMID- 22134149
TI  - Social and environmental predictors of plasma HIV RNA rebound among injection
      drug users treated with antiretroviral therapy.
AB  - INTRODUCTION: Evidence is needed to improve HIV treatment outcomes for
      individuals who use injection drugs (IDU). Although studies have suggested higher
      rates of plasma viral load (PVL) rebound among IDU on antiretroviral therapy
      (ART), risk factors for rebound have not been thoroughly investigated. METHODS:
      We used data from a long-running community-recruited prospective cohort of IDU in
      Vancouver, Canada, linked to comprehensive ART and clinical monitoring records.
      Using proportional hazards methods, we modeled the time to confirmed PVL rebound
      above 1000 copies per milliliter among IDU on ART with sustained viral
      suppression, defined as 2 consecutive undetectable PVL measures. RESULTS: Between
      1996 and 2009, 277 individuals had sustained viral suppression. Over a median
      follow-up of 32 months, 125 participants (45.1%) experienced at least 1 episode
      of virologic failure for an incidence of 12.6 [95% confidence interval (CI): 10.5
      to 15.0] per 100 person-years. In a multivariate model, PVL rebound was
      independently associated with sex-trade involvement [adjusted hazard ratio (AHR)
      = 1.40, 95% CI: 1.08 to 1.82) and recent incarceration (AHR = 1.83, 95% CI: 1.33
      to 2.52). Methadone maintenance therapy (AHR = 0.79, 95% CI: 0.66 to 0.94) was
      protective. No measure of illicit drug use was predictive. CONCLUSIONS: In this
      setting of free ART, several social and environmental factors predicted higher
      risks of viral rebound among IDU, including sex-trade involvement and
      incarceration. These findings should help inform efforts to identify individuals
      at risk of viral rebound and targeted interventions to treat and retain
      individuals in effective ART.

PMID- 22134151
TI  - Electrocautery ablation of high-grade anal squamous intraepithelial lesions in
      HIV-negative and HIV-positive men who have sex with men.
AB  - BACKGROUND: Anal squamous cell carcinoma (ASCC) incidence has been rising over
      the past decade, most dramatically in HIV-positive men who have sex with men
      (MSM). We aimed to identify a novel in-office approach for ablating high-grade
      anal intraepithelial neoplasia (HGAIN), the believed precursor lesion to ASCC.
      MATERIALS AND METHODS: We performed a retrospective analysis of medical records
      from a New York City surgical practice, identifying patients with HGAIN treated
      with electrocautery ablation (ECA) and followed for at least 5 months with high
      resolution anoscopy, biopsies, and/or cytology. We sought to determine HGAIN
      recurrence and progression to ASCC after ECA. RESULTS: Two hundred thirty-two
      MSM, 132 HIV positive and 100 HIV negative, with median follow-up of 19.0 and
      17.5 months, respectively, met inclusion criterion. In HIV-negative and HIV
      positive MSM, the probability of curing a lesion after first ECA was 85% and 75%,
      respectively. Over follow-up, 53% of HIV-negative and 61% of HIV-positive
      patients recurred. After first and second ECA, HIV-positive MSM were 1.28 times
      (P = 0.16) and 2.34 times (P = 0.009) more likely to recur than HIV-negative MSM.
      The majority of recurrence was due to development of additional lesions at
      untreated sites (metachronous recurrence). One patient (0.4%) developed ASCC. At
      last visit, 83% of HIV-negative and 69% of HIV-positive patients were HGAIN free.
      CONCLUSIONS: ECA is an effective treatment for HGAIN, with fewer patients
      progressing to ASCC than predicted with expectant management. HIV-positive
      patients are significantly more likely to recur than HIV-negative patients.

PMID- 22134153
TI  - A reassessment of LPS/indomethacin/pregnenolone combination therapy after spinal
      cord injury in rats.

PMID- 22134152
TI  - Lipid profiles in young HIV-infected children initiating and changing
      antiretroviral therapy.
AB  - BACKGROUND: Both HIV infection and antiretroviral therapy are associated with
      dyslipidemias in adults, but there are fewer data on outcomes in young children.
      Here we examined lipid profile changes in a cohort of young children before and
      after suppression on an initial ritonavir-boosted lopinavir (LPV/r)-based regimen
      and after switch to a nevirapine (NVP)-based regimen. METHODS: One hundred ninety
      five HIV-infected children who initiated LPV/r-based therapy when <24 months of
      age at 1 site in Johannesburg, South Africa, and who achieved viral suppression
      (<400 copies/mL sustained for >= 3 months) were randomized to either continue on
      the LPV/r-based regimen (n = 99) or to switch to a NVP-based regimen (n = 96).
      Nonfasting concentrations of total cholesterol (TC), low-density lipoprotein,
      high-density lipoprotein (HDL), and triglycerides (TG) were measured
      pretreatment, at randomization when suppressed, and at 9, 20, and 31 months
      postrandomization. RESULTS: Median age at treatment initiation was 9 months, and
      the initial regimen was maintained for an average of 9 months before
      randomization. TC, low-density lipoprotein, and HDL increased from pretreatment
      to randomization (P < 0.0001) and TC/HDL ratio and TG decreased (P < 0.0001).
      After switching to NVP, HDL was significantly higher (P < 0.02) and TC/HDL and TG
      significantly lower (P < 0.0001) through 31 months postswitch relative to
      remaining on the LPV/r-based regimen. CONCLUSION: Initiating antiretroviral
      therapy was associated with changes to a more favorable lipid profile in young
      children. Switching from a LPV/r-based regimen to a NVP-based regimen accentuated
      and continued these improvements. Investigation of safe and effective methods for
      managing dyslipidemias in children of different ages in resource-limited settings
      is warranted.

PMID- 22134154
TI  - Basal ganglia output to the PPN, a commentary.

PMID- 22134155
TI  - Experimental mouse tumour models: what can be learnt about human cancer
      immunology?
AB  - The recent demonstration that cancer immunotherapy extends patient survival has
      reinvigorated interest in elucidating the role of immunity in tumour
      pathogenesis. Experimental mouse tumour models have provided key mechanistic
      insights into host antitumour immune responses, and these have guided the
      development of novel treatment strategies. To accelerate the translation of these
      findings into clinical benefits, investigators need to gain a better
      understanding of the strengths and limitations of mouse model systems as tools
      for deciphering human antitumour immune responses.

PMID- 22134156
TI  - Low morbidity and mortality after stenting for malignant bowel obstruction.
AB  - BACKGROUND: The difference in mortality between emergency and elective surgery
      for malignant colonic obstruction is more than 5% in healthy patients below the
      age of 65 and increases with age to around 20%. Emergency surgery can be avoided
      by endoscopic placement of a self-expandable metal stent (SEMS). AIM: To evaluate
      the effectiveness and safety of SEMS as 'bridge to surgery'. METHOD: Between
      January 2001 and July 2008, SEMS were placed for acute malignant colonic
      obstruction in 45 patients (median age 72 years, range 35-91). RESULTS: The
      procedure was technically successful in 43 patients (94%) with resolution of
      obstructive symptoms within 48 h in 87% of the patients. No perforations occurred
      during the procedure or while awaiting surgery. Two (4%) patients required a
      second endoscopic procedure. All patients underwent a single-stage surgical
      procedure. Postoperative mortality was 2.2% (n = 1). Histology showed advanced
      colorectal cancer (T3-4N1-2M0-1) in 75% of the patients. CONCLUSION: SEMS
      placement is a safe and effective procedure as bridge to surgery in patients
      presenting with colonic obstruction due to colorectal malignancy. This procedure
      carries a risk of serious complications well below that of the reported
      difference in mortality between emergency an elective surgery.

PMID- 22134157
TI  - A new approach to the ferritin iron core growth: influence of the H/L ratio on
      the core shape.
AB  - An electron microscopy study, in combination with modeling and image simulation,
      of four different reconstituted ferritin samples: recombinant human H and L
      homopolymers, and H and L heteropolymers of native L-subunit-rich horse spleen
      and H-subunit-rich human heart ferritins, points out the existence of a
      correlation between iron core shape and protein shell.

PMID- 22134158
TI  - Onion slice shaped assembled ZnS quantum wires.
AB  - Ultra-narrow wurtzite ZnS quantum wires assembled towards an onion slice shape
      are synthesized in water using a simple hydrothermal procedure. Wires are formed
      through an oriented attachment mechanism from wurtzite ZnS spherical particles.
      Strong confinement effect originated from the narrow width was observed and holds
      promise for use in broad optoelectronic device application.

PMID- 22134159
TI  - CeO2 nanoplates with a hexagonal structure and their catalytic applications in
      highly selective hydrogenation of substituted nitroaromatics.
AB  - CeO(2) nanoplates with a new hexagonal crystal structure (a = 15.30 A and c =
      6.24 A) and uniform shape were synthesized and used as supports, showing high
      chemoselectivity for the catalytic hydrogenation of substituted nitroaromatics
      without sacrificing conversion under mild conditions.

PMID- 22134160
TI  - "The support I need": women's experiences of social support after having received
      breast cancer diagnosis and awaiting surgery.
AB  - BACKGROUND: Social support is associated with a better adjustment to breast
      cancer, whereas inadequate social support increases psychological distress.
      However, the period between diagnosis and surgery is particularly stressful, and
      few studies have addressed the significance of social support in this period.
      OBJECTIVE: The purpose of this study was to describe women's individual
      experiences of social support after having received a breast cancer diagnosis and
      awaiting surgery. METHODS: A qualitative descriptive design was used. Individual
      semistructured interviews were conducted the day before surgery with 21 women
      aged 41 to 73 years with newly diagnosed breast cancer at a Norwegian university
      hospital. RESULTS: Methods of qualitative meaning condensation analysis revealed
      5 themes: available support, information and advice, care, having confidants, and
      balancing distance and closeness. Knowing that both family and healthcare
      professionals were available and caring gave a sense of security. Social support
      gave strength, although too much could be experienced as difficult and
      frightening. The women needed a balance between distance from and closeness to
      their social network. Both professional information and someone professional with
      whom to talk personally were essential. CONCLUSIONS: Social support is an
      important resource for women with breast cancer but can be a double-edged sword
      as the network's offered support can sometimes be a burden. IMPLICATIONS FOR
      PRACTICE: Healthcare professionals could call each patient, encourage the
      patients to call if they want, and, if preferred, offer face-to-face
      consultations for women with breast cancer awaiting surgery. This contact should
      be a supportive, informative, and confidential available resource.

PMID- 22134161
TI  - Phosphate glass fibres and their role in neuronal polarization and axonal growth
      direction.
AB  - Phosphate glass fibres with composition 50P(2)O(5)-30CaO-9Na(2)O-3SiO(2)-3MgO-(5
      x)K(2)O-xTiO(2)mol.% (x=0, 2.5, 5, respectively coded as TiPS(0), TiPS(2.5) and
      TiPS(5)) were drawn following the preform drawing approach. A 20-day solubility
      test in bi-distilled water was carried out on glass fibres with different
      compositions and diameters ranging between 25 and 82 MUm. The results show that
      the glass composition, the initial fibre diameter and the thermal treatment are
      the main factors influencing the dissolution kinetics and that the fibres
      maintain their structural integrity and composition during dissolution.
      Biological tests were carried out on aligned TiPS(2.5) glass fibres using
      Neonatal Olfactory Bulb Ensheathing Cell Line (NOBEC) and Dorsal Root Ganglia
      (DRG) neurons. The fibres showed to be permissive substrates for cell adhesion
      and proliferation. The aligned configuration of the fibres seemed to provide a
      directional cue for growing axons of DRG neurons, which showed to sprout and grow
      long neurites along the fibre axis direction. These promising findings encourages
      further studies to evaluate the potential use of resorbable glass fibres (e.g.in
      combination with a nerve guidance tube) for the enhancement of the peripheral
      nerve healing with the role of supporting and guiding the cells involved in the
      nerve regeneration.

PMID- 22134162
TI  - Sub-lamellar microcracking and roles of canaliculi in human cortical bone.
AB  - Bone is a tough biological material. It is generally accepted that bone's
      toughness arises from its unique hierarchical structure, which in turn
      facilitates distributed microcracking prior to fracture. Yet, there has been
      limited progress on the detailed roles of the structural elements in the
      microcracking process. The present study examines the structure-microcracking
      relations at the lamellar and sub-lamellar levels of human cortical bone
      subjected to compressive loading. Laser scanning confocal microscopy revealed a
      clear influence of the local structure and porosity of the Haversian systems'
      lamellae on microcrack development. In particular, crack initiation and growth
      under transverse compression were associated with stress concentration at
      canaliculi. Later stages of microcracking showed extensive sub-lamellar cracks
      forming cross-hatched patterns and regularly spaced 0.5-1.7 MUm apart. The
      density, size and regularity of the crack patterns suggest enhanced inelastic
      deformation capacity through cracking control at the level of mineralized
      collagen fibril bundles. The present study thus improves the current
      understanding of the nature of inelastic deformation and microcracking in bone
      and further suggests that bone's resistance to fracture is achieved through
      microcrack control at multiple length scales.

PMID- 22134163
TI  - Adhesion, phenotypic expression, and biosynthetic capacity of corneal keratocytes
      on surfaces coated with hyaluronic acid of different molecular weights.
AB  - In ophthalmology, hyaluronic acid (HA) is an important extracellular matrix (ECM)
      component and is appropriate for use in generating a microenvironment for cell
      cultivation. The aim of this work was to evaluate the rabbit corneal keratocyte
      (RCK) growth in response to HA coatings under serum-free conditions. After
      modification with HA of varying molecular weights (MWs: 35-1500kDa), the surfaces
      were characterized by atomic force microscopy and contact angle measurements, and
      were used for cell culture studies. Our data indicated that the substrates coated
      with higher negatively charged HA become rougher and are more hydrophilic,
      resulting in the decrease of cell adhesion and cell-matrix interaction. This
      early cellular event was likely responsible for the determination of keratocyte
      configuration. Additionally, for the growth of RCKs on dry HA coatings with
      surface roughness of 1.1-1.7 nm, a strong cell-cell interaction was observed,
      which may facilitate the formation of multicellular spheroid aggregates and
      maintenance of mitotically quiescent state. At each culture time point from 1 to
      5 days, a better biosynthetic capacity associated with a higher prevalence of
      elevated ECM production was found for the cells in a spherical configuration.
      Irrespective of polysaccharide MW of surface coatings, the RCKs presented good
      viability without hypoxia-induced death. As compared with a monolayer of adherent
      keratocytes on tissue culture polystyrene plates and low MW HA-modified samples,
      the cell spheroids (76-110 MUm in diameter) showed significantly higher
      expressions of keratocan and lumican and lower expressions of biglycan, similar
      to those of keratocytes in vivo. Moreover, the expression levels of corneal
      crystallin aldehyde dehydrogenase (7-9-fold increase) and nestin (10-16-fold
      increase) were greater in larger-sized spheroids, indicating higher ability to
      maintain cellular transparency and self-renewal potential. It is concluded that
      the cultured RCKs on surfaces coated with HA of different MWs can sense ECM cues,
      and the multicellular spheroids may potentially be used for corneal stromal
      tissue engineering applications.

PMID- 22134164
TI  - Assessing the corrosion of biodegradable magnesium implants: a critical review of
      current methodologies and their limitations.
AB  - Magnesium (Mg) and its alloys have been intensively studied as biodegradable
      implant materials, where their mechanical properties make them attractive
      candidates for orthopaedic applications. There are several commonly used in vitro
      tests, from simple mass loss experiments to more complex electrochemical methods,
      which provide information on the biocorrosion rates and mechanisms. The various
      methods each have their own unique benefits and limitations. Inappropriate test
      setup or interpretation of in vitro results creates the potential for flawed
      justification of subsequent in vivo experiments. It is therefore crucial to fully
      understand the correct usages of each experiment and the factors that need to be
      considered before drawing conclusions. This paper aims to elucidate the main
      benefits and limitations for each of the major in vitro methodologies that are
      used in examining the biodegradation behaviour of Mg and its alloys.

PMID- 22134165
TI  - Durable donor engraftment after radioimmunotherapy using alpha-emitter astatine
      211-labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell
      transplantation.
AB  - To reduce toxicity associated with external gamma-beam radiation, we investigated
      radioimmunotherapy with an anti-CD45 mAb labeled with the alpha-emitter, astatine
      211 ((211)At), as a conditioning regimen in dog leukocyte antigen-identical
      hematopoietic cell transplantation (HCT). Dose-finding studies in 6 dogs treated
      with 100 to 618 MUCi/kg (211)At-labeled anti-CD45 mAb (0.5 mg/kg) without HCT
      rescue demonstrated dose-dependent myelosuppression with subsequent autologous
      recovery, and transient liver toxicity in dogs treated with (211)At doses less
      than or equal to 405 MUCi/kg. Higher doses of (211)At induced clinical liver
      failure. Subsequently, 8 dogs were conditioned with 155 to 625 MUCi/kg (211)At
      labeled anti-CD45 mAb (0.5 mg/kg) before HCT with dog leukocyte antigen-identical
      bone marrow followed by a short course of cyclosporine and mycophenolate mofetil
      immunosuppression. Neutropenia (1-146 cells/MUL), lymphopenia (0-270 cells/MUL),
      and thrombocytopenia (1500-6560 platelets/MUL) with prompt recovery was observed.
      Seven dogs had long-term donor mononuclear cell chimerism (19%-58%), whereas 1
      dog treated with the lowest (211)At dose (155 MUCi/kg) had low donor mononuclear
      cell chimerism (5%). At the end of follow-up (18-53 weeks), only transient liver
      toxicity and no renal toxicity had been observed. In conclusion, conditioning
      with (211)At-labeled anti-CD45 mAb is safe and efficacious and provides a
      platform for future clinical trials of nonmyeloablative transplantation with
      radioimmunotherapy-based conditioning.

PMID- 22134166
TI  - Platelet TGF-beta1 contributions to plasma TGF-beta1, cardiac fibrosis, and
      systolic dysfunction in a mouse model of pressure overload.
AB  - Circulating platelets contain high concentrations of TGF-beta1 in their alpha
      granules and release it on platelet adhesion/activation. We hypothesized that
      uncontrolled in vitro release of platelet TGF-beta1 may confound measurement of
      plasma TGF-beta1 in mice and that in vivo release and activation may contribute
      to cardiac pathology in response to constriction of the transverse aorta, which
      produces both high shear and cardiac pressure overload. Plasma TGF-beta1 levels
      in blood collected from C57Bl/6 mice by the standard retro-bulbar technique were
      much higher than those obtained when prostaglandin E1 was added to inhibit
      release or when blood was collected percutaneously from the left ventricle under
      ultrasound guidance. Even with optimal blood drawing, plasma TGF-beta1 was lower
      in mice rendered profoundly thrombocytopenic or mice with selectively low levels
      of platelet TGF-beta1 because of megakaryocyte-specific disruption of their TGF
      beta1 gene (Tgfb1(flox)). Tgfb1(flox) mice were also partially protected from
      developing cardiac hypertrophy, fibrosis, and systolic dysfunction in response to
      transverse aortic constriction. These studies demonstrate that plasma TGF-beta1
      levels can be assessed accurately, but it requires special precautions; that
      platelet TGF-beta1 contributes to plasma levels of TGF-beta1; and that platelet
      TGF-beta1 contributes to the pathologic cardiac changes that occur in response to
      aortic constriction.

PMID- 22134167
TI  - Expansion of CD8+ T cells lacking Sema4D/CD100 during HIV-1 infection identifies
      a subset of T cells with decreased functional capacity.
AB  - Sema4D, also known as CD100, is a constitutively expressed immune semaphorin on T
      cells and NK cells. CD100 has important immune regulatory functions that improve
      antigen-specific priming by antigen-presenting cells, and can also act as a
      costimulatory molecule on T cells. We investigated the consequence of HIV-1
      infection on CD100 expression by T cells, and whether CD100 expression signifies
      functionally competent effector cells. CD100 expression on T cells from healthy
      individuals was compared with HIV-1-infected subjects including elite
      controllers, noncontrollers, and patients receiving antiretroviral therapy. The
      frequency and fluorescence intensity of CD100 on CD8(+) and CD4(+) T cells were
      decreased during HIV-1 infection. Furthermore, the absolute number of CD100
      expressing CD8(+) T cells was positively associated with the magnitude of HIV-1
      specific T-cell responses. CD8(+) T cells lacking CD100 expression were
      functionally impaired and present in increased numbers in HIV-1-infected
      individuals. The number of CD100(-)CD8(+) T cells positively correlated with T
      cell immunosenescence, immune activation, and viral load. Loss of CD100
      expression appears to result from direct antigen stimulation, as in vitro
      cytokine exposure and viral replication did not significantly impact CD100
      expression. These data suggest that loss of CD100 expression probably plays an
      important role in dysfunctional immunity in HIV-1 infection.

PMID- 22134168
TI  - Notch promotes vascular maturation by inducing integrin-mediated smooth muscle
      cell adhesion to the endothelial basement membrane.
AB  - Vascular development and angiogenesis initially depend on endothelial tip cell
      invasion, which is followed by a series of maturation steps, including lumen
      formation and recruitment of perivascular cells. Notch ligands expressed on the
      endothelium and their cognate receptors expressed on perivascular cells are
      involved in blood vessel maturation, though little is known regarding the Notch
      dependent effectors that facilitate perivascular coverage of nascent vessels.
      Here, we report that vascular smooth muscle cell (VSMC) recognition of the Notch
      ligand Jagged1 on endothelial cells leads to expression of integrin alphavbeta3
      on VSMCs. Once expressed, integrin alphavbeta3 facilitates VSMC adhesion to VWF
      in the endothelial basement membrane of developing retinal arteries, leading to
      vessel maturation. Genetic or pharmacologic disruption of Jagged1, Notch,
      alphavbeta3, or VWF suppresses VSMC coverage of nascent vessels and arterial
      maturation during vascular development. Therefore, we define a Notch-mediated
      interaction between the developing endothelium and VSMCs leading to adhesion of
      VSMCs to the endothelial basement membrane and arterial maturation.

PMID- 22134169
TI  - AUF-1 and YB-1 are critical determinants of beta-globin mRNA expression in
      erythroid cells.
AB  - The normal accumulation of beta-globin protein in terminally differentiating
      erythroid cells is critically dependent on the high stability of its encoding
      mRNA. The molecular basis for this property, though, is incompletely understood.
      Factors that regulate beta-globin mRNA within the nucleus of early erythroid
      progenitors are unlikely to account for the constitutively high half-life of beta
      globin mRNA in the cytoplasm of their anucleate erythroid progeny. We conducted
      in vitro protein-RNA binding analyses that identified a cytoplasm-restricted beta
      globin messenger ribonucleoprotein (mRNP) complex in both cultured K562 cells and
      erythroid-differentiated human CD34(+) cells. This novel mRNP targets a specific
      guanine-rich pentanucleotide in a region of the beta-globin 3'untranslated region
      that has recently been implicated as a determinant of beta-globin mRNA stability.
      Subsequent affinity-enrichment analyses identified AUF-1 and YB-1, 2 cytoplasmic
      proteins with well-established roles in RNA biology, as trans-acting components
      of the mRNP. Factor-depletion studies conducted in vivo demonstrated the
      importance of the mRNP to normal steady-state levels of beta-globin mRNA in
      erythroid precursors. These data define a previously unrecognized mechanism for
      the posttranscriptional regulation of beta-globin mRNA during normal
      erythropoiesis, providing new therapeutic targets for disorders of beta-globin
      gene expression.

PMID- 22134171
TI  - A new vasculitis activity score for predicting death in myeloperoxidase
      antineutrophil cytoplasmic antibody-associated vasculitis patients.
AB  - BACKGROUND/AIMS: Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)
      positive microscopic polyangiitis patients with renal involvement have been shown
      to have a progressive clinical course. In this study, we compared the clinical
      utility of the Japanese Vasculitis Activity Score (JVAS) with the Birmingham
      Vasculitis Activity Score (BVAS) for predicting death in patients with MPO-ANCA
      associated renal involvement. METHODS: Sixty-nine patients with MPO-ANCA
      associated vasculitis with renal involvement (22 males and 47 females, age 69.8
      +/- 8.7 years) were enrolled in this study. We retrospectively investigated which
      score was better for predicting the poor prognosis of patients. RESULTS: The
      mortality rate of the patients within 2 years after disease onset was 33%
      (23/69). JVAS was not correlated with BVAS. Univariate logistic regression
      analysis for death showed that the odds ratio (OR) of JVAS was statistically
      significant (OR 1.76, 95% confidence interval, CI, 1.29-2.41, p < 0.001), while
      that of BVAS was not (OR 1.07, 95% CI 0.98-1.16, p = 0.14). Moreover, a
      multivariate model showed that JVAS was an independent determinant of death (OR
      1.59, 95% CI 1.12-2.25, p = 0.009). The area under the receiver operating
      characteristic curve for JVAS was 0.778, which was significantly larger (p =
      0.02) than that for BVAS (0.586). The estimated optimal cut-off point of JVAS for
      the prediction of death was 5. At this point, the sensitivity was 82.6% and the
      specificity was 60.9%. CONCLUSION: We demonstrated that compared with BVAS, JVAS
      was a simpler and more reliable measure for predicting death in patients with MPO
      ANCA-associated vasculitis with renal involvement.

PMID- 22134170
TI  - AAV-mediated gene transfer in the perinatal period results in expression of FVII
      at levels that protect against fatal spontaneous hemorrhage.
AB  - We explored adeno-associated viral vector (AAV)-mediated gene transfer in the
      perinatal period in animal models of severe congenital factor VII (FVII)
      deficiency, a disease associated with early postnatal life-threatening
      hemorrhage. In young adult mice with plasma FVII < 1% of normal, a single tail
      vein administration of AAV (1 * 10(13) vector genomes [vg]/kg) resulted in
      expression of murine FVII at 266% +/- 34% of normal for >= 67 days, which
      mediated protection against fatal hemorrhage and significantly improved survival.
      Codon optimization of human FVII (hFVIIcoop) improved AAV transgene expression by
      37-fold compared with the wild-type hFVII cDNA. In adult macaques, a single
      peripheral vein injection of 2 * 10(11) vg/kg of the hFVIIcoop AAV vector
      resulted in therapeutic levels of hFVII expression that were equivalent in males
      (10.7% +/- 3.1%) and females (12.3% +/- 0.8%). In utero delivery of this vector
      in the third trimester to fetal monkeys conferred expression of hFVII at birth of
      20.4% +/- 3.7%, with a gradual decline to > 1% by 7 weeks. Re-administration of
      an alternative serotype at 12 months postnatal age increased hFVII levels to 165%
      +/- 6.2% of normal, which remained at therapeutic levels for a further 28 weeks
      without toxicity. Thus, perinatal AAV-mediated gene transfer shows promise for
      disorders with onset of pathology early after birth.

PMID- 22134172
TI  - A new myocardial perfusion scintigraphy stress protocol combining dipyridamole
      dobutamine-atropine.
AB  - BACKGROUND: Pharmacological stress is often used, and the drugs most frequently
      utilized are dipyridamole (Dip) and dobutamine (Dob). We aimed to evaluate the
      safety and the results obtained with a new protocol associating Dip, Dob, and
      atropine, compared with the Dip protocol. METHODS: Thirty-two patients underwent
      rest Tl/Dip stress Tc-sestamibi myocardial perfusion tomography on the same day.
      Dip was administered intravenously (0.56 mg/kg) for 4 min, and Tc-sestamibi was
      injected 3 min after the end of the Dip injection. On another day, patients
      received the same Dip dose, immediately followed by the infusion of Dob [20
      MUg/kg/min for the first 2 min and 40 MUg/kg/min in the next 2 min, with atropine
      (1 mg) given in the interval between the two Dob doses]. Images were acquired
      with a two-detector camera. In a 17-segment model of the left ventricle, each
      segment was automatically scored 0-4 (normal to absent radiotracer activity), and
      perfusion scores were obtained as the sum of stress score and sum of rest
      segmental score (SSS and SRS, respectively) and the difference between them
      [summed difference score (SDS)]. All scans were interpreted by two experienced
      physicians as either definitely normal, probably normal, probably abnormal, or
      definitely abnormal. RESULTS: No serious complication was found independently of
      the protocol used. Heart rate and systolic and diastolic blood pressure were
      similar in both protocols at the basal level. Maximum heart rate (126 +/- 21 vs.
      82.7 +/- 13.6, P<0.001) and the double product (18816 +/- 4194 vs. 11449 +/-
      2438, P<0.001) showed a significant increase in the tests that used Dob and
      atropine compared with the Dip protocol. Stress studies with Dip-Dob had higher
      SSS compared with the Dip protocol (9.4 +/- 10.1 vs. 7.7 +/- 8.8, P<0.001). SDS
      was also higher in the Dip-Dob protocol than in the Dip protocol (6.1 +/- 6.8 and
      4.8 +/- 5.8, respectively, P< 0.001). CONCLUSION: This work shows that a new
      protocol of pharmacological stress with a combination of Dip, Dob, and atropine
      is safe, easy to administer, and results in larger stress-induced defect size and
      reversibility of myocardial perfusion.

PMID- 22134173
TI  - Quantification and reduction of the collimator-detector response effect in SPECT
      by applying a system model during iterative image reconstruction:  a simulation
      study.
AB  - BACKGROUND: Detector blurring and non-ideal collimation decrease the spatial
      resolution of the single-photon emission computed tomography (SPECT) images.
      Iterative reconstruction algorithms such as ordered subsets expectation
      maximization (OSEM) can incorporate degrading factors during reconstruction. We
      investigated the quantitative errors associated with poor SPECT resolution and
      evaluated the importance of two-dimensional (2D) and three-dimensional (3D)
      resolution recovery by modelling system response during iterative image
      reconstruction. METHODS: Different phantoms consisted of the NURBS-based cardiac
      torso (NCAT) liver phantom with small tumors, the Zubal brain phantom and the
      NCAT heart phantom were used in this study. Monte Carlo simulation was used to
      create SPECT projections. Gaussian functions were used to model collimator
      detector response (CDR). Modeled CDRs were applied during OSEM. Both noise-free
      and noisy projections were created. RESULTS: Even with noise-free projections,
      conventional OSEM algorithm provided limited quantitative accuracy compared to
      both 2D and 3D resolution recovery. The 3D implementation of resolution recovery,
      however, yielded superior results compared to its 2D implementation. For the
      liver phantom, the ability to distinguish small tumors in both transverse and
      axial planes was improved. For the brain phantom, gray to white matter activity
      ratio was increased from 3.14 +/- 0.04 in simple OSEM to 3.84 +/- 0.06 in 3D
      OSEM. For the NCAT heart phantom, 3D resolution recovery, results in images with
      thinner wall and higher contrast for different noise levels. CONCLUSION: There
      are considerable quantitative errors associated with CDR, especially when the
      size of the target is comparable with the spatial resolution of the system.
      Between different reconstruction algorithms, 3D OSEM that consider the 3D nature
      of CDR, improve both the visual quality and the quantitative accuracy of any
      SPECT studies.

PMID- 22134174
TI  - Psychostimulant-related deaths among former inmates.
AB  - OBJECTIVES: Psychostimulants are highly addictive and their use is increasing.
      Little is known about psychostimulant-related deaths. This study identified
      characteristics, risk factors, and contributing substances reported upon death
      among former prison inmates who died from a psychostimulant-related death.
      METHODS: This retrospective cohort study of released inmates from 1999 to 2003 (N
      = 30,237) linked data from the Washington State Department of Corrections with
      the National Death Index. We examined characteristics of individuals who died
      with psychostimulants listed among their causes of death. These were categorized
      into 3 groups: (1) noncocaine psychostimulants, (2) cocaine only, and (3) all
      psychostimulants. Cox proportional hazards regression determined risk factors for
      death in each group, and the risk of death in the first 2 weeks after release
      from prison RESULTS: Of the 443 inmates who died, 25 (6%) had noncocaine
      psychostimulants listed among their causes of death. Six of these 25 deaths had
      both noncocaine psychostimulants and cocaine listed among their causes-of-death.
      Most of the former inmates who died with noncocaine psychostimulants were male (n
      = 21, 84%) and non-Hispanic white (88%, n = 22). Cocaine only was listed among
      the causes-of-death for 49 former inmates; most were male (n = 35, 71%) and non
      Hispanic white (n = 27, 55%). Longer length of incarceration was associated with
      a reduced risk of death from any psychostimulant use (hazard ratio = 0.76,
      confidence interval = 0.63-0.920 for each additional year of incarceration) and
      from use of noncocaine psychostimulants (hazard ratio = 0.42, 95% CI = 0.22
      0.80). Risk of death was highest during the first 2 weeks postrelease for cocaine
      only-related deaths (incidence mortality ratio = 1224.0, confidence interval =
      583-1865). CONCLUSIONS: Former prisoners have a significant risk of death from
      psychostimulants, especially within the first 2 weeks postrelease.

PMID- 22134175
TI  - Impact of methadone with versus without drug abuse counseling on HIV risk: 4- and
      12-month findings from a clinical trial.
AB  - OBJECTIVE: Human immunodeficiency virus (HIV)-risk behaviors were examined at 4-
      and 12-month follow-up for 230 newly admitted methadone patients randomly
      assigned to receive either methadone only (n = 99) or methadone with drug abuse
      counseling (n = 131) in the first 4 months of treatment. METHODS: The AIDS Risk
      Assessment was administered at baseline (treatment entry) and at 4- and 12-month
      follow-up. Linear mixed model analysis examined changes in HIV drug- and sex-risk
      behaviors over the 12 months in the total sample, drug-risk behaviors in the
      subsample that reported injecting drugs at baseline (n = 110), and sex-risk
      behaviors in the subsample that reported engaging in unprotected sex at baseline
      (n = 130). RESULTS: Significant decreases over time were found in the frequencies
      of injecting, injecting with other injectors, and sharing cooker, cotton, or
      rinse water in the total sample and the injector subsample (P < 0.05). Decreases
      were also found in the frequencies of having sex without a condom either with
      someone who was not a spouse or primary partner or while high (P < 0.05) in the
      total sample and the frequencies of having sex without a condom and having sex
      without a condom while high in the unprotected-sex subsample (P < 0.05). No
      significant treatment group main effects or Treatment Group * Time interaction
      effects were found in any of the HIV-risk behaviors in the total sample or either
      subsample (P > 0.05). CONCLUSIONS: During the first 12 months of treatment,
      providing drug abuse counseling with methadone compared with providing methadone
      alone was not associated with significant changes in HIV-risk behaviors for
      methadone maintenance patients.

PMID- 22134176
TI  - Regiospecific beta-lactam ring-opening/recyclization reactions of N-aryl-3
      spirocyclic-beta-lactams catalyzed by a Lewis-Bronsted acids combined superacid
      catalyst system: a new entry to 3-spirocyclicquinolin-4(1H)-ones.
AB  - The regiospecific beta-lactam ring-opening/recyclization reaction of N-aryl-3
      spirocyclic-beta-lactams, made by the one-pot cyclization reaction of
      acetoacetanilides, has been achieved for the first time using a Lewis-Bronsted
      acids combined superacid catalyst system, thus providing an efficient entry to 3
      spirocyclicquinolin-4(1H)-ones. A mechanism involving superacid-catalysis was
      proposed.

PMID- 22134177
TI  - Characterization of two different melatonin binding sites in peripheral tissues
      of the teleost Tinca tinca.
AB  - The aim of the present study was to localize and characterize 2-iodo-melatonin
      ([(125)I]Mel) binding sites in peripheral tissues of the teleost Tinca tinca. A
      wide distribution of [(125)I]Mel binding sites in peripheral locations of the
      tench is found, with highest densities being measured in the heart, gills and
      kidney, and low density of [(125)I]Mel binding sites in gastrointestinal tract,
      spleen, liver and gonads. Saturation, kinetics, and pharmacological approaches
      revealed the presence of, at least, two different [(125)I]Mel binding sites in
      the tench peripheral tissues. The unique characterized subtype in the heart
      fulfils all the criteria for a canonical melatonin receptor belonging to MT(1)
      family (the binding is saturable, reversible, and inhibited by GTP analogs), and
      gives support for the presence of a functional melatonin receptor in the heart of
      the tench. In contrast, kinetic and pharmacological studies in the kidney
      revealed the preponderance of a melatonin binding site belonging to the MT(3)
      like receptor subtype. Moreover, the decrease of specific binding in both, heart
      and kidney membranes, and the decrease of affinity in the kidney, produced by the
      addition of a non-hydrolysable GTP analog, and sodium cations suggest the
      presence of G(i/o)-proteins (that mediate inhibition of cAMP formation) coupled
      to such melatonin binding sites. Our results also point to different G(i/o)
      proteins involved in the underlying mechanism of melatonin binding sites
      activation in the kidney. Additionally, the kinetics of [(125)I]Mel binding in
      kidney membrane preparations is a highly thermosensitive process, being necessary
      to perform the assays at 4  degrees C since the equilibrium was not reached at 25
      degrees C assay temperature. The time needed to complete association of
      [(125)I]Mel at such low temperature is only 15s, whereas 100s is required to
      displace [(125)I]Mel specific binding by the unlabeled melatonin in kidney
      membranes. Present results support previous reports on melatonin effects in the
      regulation of different physiological functions in teleost (as cardiovascular
      physiology and osmoregulation) acting through peripheral specific receptors.

PMID- 22134178
TI  - Effects of hydrostatic pressure on monoaminergic activity in the brain of a
      tropical wrasse, Halicoeres trimaculatus: possible implication for controlling
      tidal-related reproductive activity.
AB  - Most wrasse species in tropical waters exhibit daily spawning synchrony with a
      preference for high tide. Fish perceive tidal rhythm cues through sensory organs
      and activate the brain-pituitary-gonadal endocrine axis for synchronous gonadal
      maturation, although how the tidal-related spawning cycle is controlled
      endogenously is not known. The purpose of this study was to examine whether
      hydrostatic pressure has an impact on brain monoamine levels and reproductive
      activities in the threespot wrasse Halichoeres trimaculatus. The contents of
      dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5
      hydroxyindoleacetic acid (5-HIAA) in the brain were measured using high
      performance liquid chromatography and an electrochemical detection system.
      Exposing the fish to hydrostatic pressure occurring at a 3-m depth (~30 kPa)
      resulted in an increase in 5-HIAA/5-HT over 3h and a decrease in DOPAC/DA over
      6h. No changes in gonadosomatic index or oocyte diameter were observed between
      the groups when female fish were reared at 0-m and 3-m depth for 3h. Hydrostatic
      pressure did not alter pituitary mRNA abundance of follicle stimulating hormone
      beta or luteinizing hormone-beta. However, in vitro culture of ovaries from
      pressurized fish in the presence of human chorionic gonadotropin resulted in an
      increase in 17alpha,20beta-dihydroxy-4-pregnen-3-one in the medium. These results
      suggest that hydrostatic pressure activates oocyte maturation through brain
      monoaminergic activity in this tropical wrasse species.

PMID- 22134179
TI  - Characterization of the estrous cycle in female beluga (Delphinapterus leucas)
      using urinary endocrine monitoring and transabdominal ultrasound: Evidence of
      facultative induced ovulation.
AB  - Recent, successful application of assisted reproductive technologies in captive
      beluga has resulted from the extensive study of male beluga reproductive biology.
      Optimization of assisted reproduction requires additional detailed knowledge of
      the female estrous cycle. Our specific objectives were to: (1) validate urinary
      immunoassays for use in this species; (2) elucidate annual ovarian cycle dynamics
      through the combined use of hormone excretion patterns and transabdominal
      ultrasound; and (3) establish whether ovulation in this species is spontaneous or
      induced by male factors. Ovulation was observed in four of 15 estrous cycles
      monitored in four adult female beluga maintained in a single-sex group. After
      introduction of a breeding male, ovulation was observed in six of seven estrous
      cycles. All estrous cycles occurred from March through June. For spontaneous
      ovulations (n=4), the inter-estrous interval was 34d (range 33-35d), with a
      follicular phase length (FPL) of 25+/-8d (mean+/-SD). For all ovulatory estrous
      cycles (with and without a breeding male), urinary estrogen conjugates (EC,
      15.3+/-7.9ng/mg Cr) and ovulatory luteinizing hormone (ovLH, 17.1+/-6.6ng/mg Cr)
      concentrations both peaked on Day 0, and EC concentrations returned to baseline
      8+/-7d later. For non-conceptive cycles, urinary progestagen (Pg) concentrations
      increased on Day 0 (3.5+/-1.7ng/mg Cr), peaked on Day+19 (19.7+/-17.1ng/mg Cr),
      and were elevated above baseline for 27+/-4d. Preovulatory follicular diameter
      and circumference on Day -2+/-2 (range: Day -4 to -1) from peak EC were 2.5+/-0.7
      and 7.8+/-1.3cm, respectively. The FPL in non-ovulatory estrous cycles (n=11)
      lasted 24+/-10d and EC concentrations gradually declined to baseline over a 21+/
      10d interval following the EC peak (27.8+/-28.8ng/mg Cr). Non-ovulatory estrous
      cycles were characterized by the absence of an ovLH surge and no concomitant
      increase in Pg concentrations above baseline excretion; the mean follicular
      diameter at or near peak EC was 3.1+/-0.8cm on Day 2 +/-3d from peak EC (range: 
      1 to +5days from peak EC). Overall, these data confirm that captive beluga
      exhibit reproductive seasonality and demonstrate that the species is a
      facultative-induced ovulator.

PMID- 22134180
TI  - Characterization of triacetyl-alpha-melanocyte-stimulating hormone in carp and
      goldfish.
AB  - A triacetyl form of alpha-melanocyte-stimulating hormone (MSH) was found in carp
      (Cyprinus carpio) and goldfish (Carassius auratus), by selective detection of
      mass profile for cell secretory granules using direct tissue matrix-assisted
      laser desorption ionization with time-of-flight mass spectrometry (MALDI-TOF MS)
      analysis during the investigation of fish pituitaries. The structure of triacetyl
      alpha-MSH in carp and goldfish was further analyzed using a collision-induced
      dissociation with electrospray ionization mass spectrometry, and determined to be
      N,O-diacetyl Ser as the N-terminal residue and O-acetyl Tyr at position 2. These
      modifications for alpha-MSH in carp and goldfish are structurally different from
      that of medaka hormone, in which [N,O-diacetyl Ser(1), O-acetyl Ser(3)]-alpha-MSH
      has been identified. The profiles of four alpha-MSH variants, des-, mono-, di-
      and tri-acetyl forms in goldfish and medaka pituitaries were also examined by
      direct tissue MALDI-TOF MS analysis, and the percentages as a total of alpha-MSH
      molecules were compared for fish reared in a white or black tank for 5 days.
      Among structural variants, diacetyl-alpha-MSH was the predominant form in
      goldfish and N-desacetyl-alpha-MSH in medaka, respectively. In both species, the
      relative level of the predominant form in the pituitary of white-adapted fish
      tended to be lower than that of black-adapted fish. In goldfish, no significant
      difference was observed in the relative content of triacetyl-alpha-MSH in both
      backgrounds, whereas the lowest content of triacetyl-alpha-MSH was found in black
      adapted medaka. These preliminary data indicate that it is difficult to elucidate
      the relations between the physiological roles and acetylated pattern of alpha-MSH
      molecule, depending on species.

PMID- 22134181
TI  - Participation of Gs-proteins in the action of relaxin-like gonad-stimulating
      substance (GSS) for 1-methyladenine production in starfish ovarian follicle
      cells.
AB  - Gonad-stimulating substance (GSS) in starfish is the only known invertebrate
      peptide hormone responsible for final gamete maturation, rendering it
      functionally analogous to gonadotropins in vertebrates. Recently, we purified GSS
      from radial nerves in the starfish Asterina pectinifera and identified the
      chemical structure as a heterodimer composed of two different peptides (A- and B
      chain) with disulfide cross-linkages. This study examined the hormonal action of
      GSS on ovarian follicle cells obtained from ovaries in growing (stage IV) and
      fully grown (stage V) stages, and particularly the mode of signal transduction.
      The action of GSS on 1-MeAde production by follicle cells in stage V was mediated
      through the production of cAMP. In contrast, GSS failed to induce 1-MeAde and
      cAMP production by follicle cells in stage IV. According to competitive
      experiments using radioiodinated and radioinert GSS, highly specific binding was
      observed in follicle cells, though their affinities and numbers in stage IV were
      inferior to those in stage V. Interestingly, Gsalpha was not detected
      immunologically in follicle cell membranes of stage IV. Gbeta was also faint in
      stage IV. Although adenylyl cyclase activity in stage V was dose-dependently
      activated by GSS in the presence of GTP, neither GSS in the presence of GTP nor
      nonhydrolyzable GTP analogs were effective on the activity in stage IV. These
      findings strongly suggest that the failure of GSS to produce 1-MeAde is because
      of a lack of Gs-proteins in follicle cells at stage IV.

PMID- 22134182
TI  - Radial force distribution changes associated with tangential force production in
      cylindrical grasping, and the importance of anatomical registration.
AB  - Radial force (F(r)) distributions describe grip force coordination about a
      cylindrical object. Recent studies have employed only explicit F(r) tasks, and
      have not normalized for anatomical variance when considering F(r) distributions.
      The goals of the present study were (i) to explore F(r) during tangential force
      production tasks, and (ii) to examine the extent to which anatomical registration
      (i.e. spatial normalization of anatomically analogous structures) could improve
      signal detectability in F(r) data. Twelve subjects grasped a vertically oriented
      cylindrical handle (diameter=6 cm) and matched target upward tangential forces of
      10, 20, and 30 N. F(r) data were measured using a flexible pressure mat with an
      angular resolution of 4.8 degrees , and were registered using piecewise-linear
      interpolation between five manually identified points-of-interest. Results
      indicate that F(r) was primarily limited to three contact regions: the distal
      thumb, the distal fingers, and the fingers' metatacarpal heads, and that, while
      increases in tangential force caused significant increases in F(r) for these
      regions, they did not significantly affect the F(r) distribution across the hand.
      Registration was found to substantially reduce between-subject variability, as
      indicated by both accentuated F(r) trends, and amplification of the test
      statistic. These results imply that, while subjects focus F(r) primarily on three
      anatomical regions during cylindrical grasp, inter-subject anatomical differences
      introduce a variability that, if not corrected for via registration, may
      compromise one's ability to draw anatomically relevant conclusions from grasping
      force data.

PMID- 22134183
TI  - Reverse engineering finger extensor apparatus morphology from measured coupled
      interphalangeal joint angle trajectories - a generic 2D kinematic model.
AB  - The interphalangeal (IP) finger joints coordinate as a mechanism when the deep
      flexor is active. This mechanism is created by the complex finger extensor
      apparatus (EA) - a confluence of end tendons of one or two extensors, radial and
      ulnar interossei, and lumbrical - which inserts as a single structure into both
      the middle and distal phalanges. Although the IP-coupling principle was well
      demonstrated more than half a century ago, the detailed relationship between EA
      morphology and IP coupling remains not well described. Main reasons are that by
      dissection the EA's fiber network loses functional consistency, while fibers
      becoming taut or slack beyond measuring resolutions complicate measuring
      functional fiber motions. To circumvent these difficulties, we present a two
      dimensional kinematic multi tendon-string EA model of fiber slackness and
      tautness through IP motion, including the retinacular and oblique retinacular EA
      ligaments. The model parameters were the strings' lengths and attachment points.
      The model's functional redundancies were resolved by individually interactively
      fitting model IP trajectories to previously measured IP trajectories of 68
      fingers. All model trajectories accurately fitted their target IP trajectories
      for proximal interphalangeal (PIP) joint ranges smaller than 25 degrees  to 45
      degrees ; about half accurately fitted over the entire IP range with the
      remaining half having maximum approximation errors between 3 degrees  to 12
      degrees , while all models again converged to target trajectories for full IP
      flexion. These accuracies suggest the model reflects real functional EA
      principles, with potential applications in biomechanical modeling, surgical
      reconstruction, rehabilitation, and prosthetic EA replacements.

PMID- 22134184
TI  - 'Intraperitoneal mesh repair of small ventral abdominal wall hernias with a
      Ventralex hernia patch': a critical note.

PMID- 22134185
TI  - Use of a novel double uterine deposition artificial insemination technique using
      low concentrations of sperm in pigs.
AB  - Currently, the three most important non-surgical artificial insemination systems
      used in pigs are the conventional, the post-cervical (IUI), and the deep
      intrauterine (DIUI) methods. In this study, a new system, termed double uterine
      deposition insemination (DUDI), which combines aspects of both IUI and DIUI, was
      evaluated. This method used a thinner, shorter and more flexible catheter than
      those normally used for DIUI and resulted in the deposition of semen post
      cervically, approximately half-way along the uterine horn, thus potentially by
      passing the threat of 'unilateral' insemination or pregnancy when using sperm of
      low concentration. The experiment was carried out over 8 weeks on a group of 166
      sows, which were divided into seven groups, inseminated with semen of varying
      concentration, using the conventional system (control group) or by DUDI. There
      were no significant differences in fertility at day 35 post-insemination between
      the controls and the various DUDI sub-groups. Only sows inseminated with 500
      million viable spermatozoa in a total of 30 mL of fluid using the DUDI system
      demonstrated decreased total litter sizes when compared to conventional
      insemination (P<0.001). While conventional insemination normally uses 2.5-3.5
      billion sperm, the findings of this study suggest that DUDI can be used under
      'field' conditions with sperm concentrations as low as 750 million spermatozoa in
      50-30 mL without any detrimental effect on fertility or litter size. DUDI may
      provide a viable, robust alternative to IUI and DIUI, and has the potential to
      become incorporated into on-farm insemination systems.

PMID- 22134186
TI  - Variation in equine management factors between riding schools with high vs. low
      insurance claims for orthopaedic injury: a field study.
AB  - Lameness is the most commonly diagnosed condition in equine veterinary practice.
      To examine whether variations in management and husbandry strategies in riding
      schools could influence wastage due to orthopaedic injury schools with high
      (HUIO) or low (LUIO) insurance claims for orthopaedic injuries (as an indirect
      measure of wastage) were compared epidemiologically using an extensive
      questionnaire and field study visits. Schools differed in management strategies
      and these influence injury rate and longevity. For horses in the LUIO schools a
      significantly longer time period had elapsed since acquisition and they had
      higher (but not statistically significant) mean ages. The employment of
      experienced managers and highly qualified chief instructors had a protective
      effect against orthopaedic injury in both LUIO and HUIO types of school. LUIO
      schools were significantly more likely to have at least 11 weeks of introductory
      work for new horses and were more likely to be under private management.

PMID- 22134187
TI  - Can tissue PCR augment the diagnostic accuracy in genitourinary tract
      tuberculosis?
AB  - PURPOSE: Conventional methods like smear and culture for Mycobacterium
      tuberculosis are of limited sensitivity and specificity. Histopathological
      examination (HPE) for the tissues obtained gives inconclusive diagnosis in the
      absence of caseous necrosis or stained acid-fast bacilli. This study was
      conducted to determine the utility of tissue PCR for diagnosing tuberculosis of
      the genitourinary tract (GUTB) and its comparative evaluation with HPE. PATIENTS
      AND METHODS: A prospective study was conducted from January 2006 to August 2009
      with 78 tissue specimens (renal, prostate, epididymis, penile and soft tissue)
      from patients with clinically suspected GUTB. All the samples were processed for
      both PCR and histopathology. RESULTS: In 68 (87.1%) samples, results for both PCR
      and HPE were coinciding. False positivity and false negativity was observed in
      5.1% (4/78) and 7.6% (6/78) samples, respectively. With HPE as the gold standard,
      PCR has shown sensitivity of 87.5% (95% CI 80.1; 91.9) and specificity of 86.7%
      (95% CI 74.9; 93.8) and positive agreement between two tests was observed as
      significant (0.7). PCR results were obtained within a mean period of 3.4 days
      while those of HPE were obtained in 7.2 days. CONCLUSIONS: Tissue PCR is a
      sensitive and specific method for obtaining early and timely diagnosis of GUTB.
      Application of tissue PCR results can augment the diagnostic accuracy in
      histopathologically labelled granulomatous inflammations.

PMID- 22134188
TI  - Nanodiamonds as photocatalysts for reduction of water and graphene oxide.
AB  - Detonated nanodiamonds (NDs) exhibit remarkable photocatalytic activity towards
      the hydrogen gas generation upon 532 nm laser pulse irradiation. Hydrogenation
      dramatically increases the quantum yield, suggesting that hydrogen-terminated
      sites work as electron reservoirs. NDs can also be used as effective
      photocatalysts to reduce graphene oxide. The resulting composites exhibit high
      and stable photocurrent generation upon visible light irradiation.

PMID- 22134192
TI  - Smooth pursuit and fixation ability in children with Tourette syndrome.
AB  - OBJECTIVE: The smooth pursuit eye movements and fixation ability of children aged
      8 to 16 years with Tourette syndrome (TS) were examined. BACKGROUND: Although
      several studies have examined the saccadic ability of patients with TS, there
      have been only a few studies examining pursuit ability in TS. METHOD: Pursuit
      gain (eye velocity/target velocity) and intrusive saccades during fixation were
      measured in children with TS-only, TS+attention deficit hyperactivity disorder
      (ADHD), and TS+ADHD+obsessive compulsive disorder (OCD), and in controls (8 to 16
      y). Two pursuit tasks and 1 fixation task were used. In random pursuit 1 (RP1),
      each step and ramp cycle began from fixation; in random pursuit 2 (RP2), each
      cycle followed the next. In the fixation task, children were required to maintain
      fixation on a center dot and ignore distractor stimuli. RESULTS: All children had
      significantly higher pursuit gains in RP2 than in RP1 when pursuing a 30
      degrees/s moving target. In addition, in RP2, the TS+ADHD+OCD group displayed
      significantly higher pursuit gains relative to the TS-only, TS+ADHD, and control
      groups. In the fixation task, the TS+ADHD group exhibited significantly more
      intrusive saccades than the TS+ADHD+OCD and control groups. CONCLUSIONS: Our
      findings support an enhanced oculomotor ability in the TS+ADHD+OCD group and the
      presence of an online gain control mechanism during ongoing pursuit. These
      findings are discussed in more detail.

PMID- 22134189
TI  - Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells
      in situ: visualizing the therapeutic effects of metformin in tumor tissue.
AB  - We have recently proposed a new mechanism for explaining energy transfer in
      cancer metabolism. In this scenario, cancer cells behave as metabolic parasites,
      by extracting nutrients from normal host cells, such as fibroblasts, via the
      secretion of hydrogen peroxide as the initial trigger. Oxidative stress in the
      tumor microenvironment then leads to autophagy-driven catabolism, mitochondrial
      dys-function, and aerobic glycolysis. This, in turn, produces high-energy
      nutrients (such as L-lactate, ketones, and glutamine) that drive the anabolic
      growth of tumor cells, via oxidative mitochondrial metabolism. A logical
      prediction of this new "parasitic" cancer model is that tumor-associated
      fibroblasts should show evidence of mitochondrial dys-function (mitophagy and
      aerobic glycolysis). In contrast, epithelial cancer cells should increase their
      oxidative mitochondrial capacity. To further test this hypothesis, here we
      subjected frozen sections from human breast tumors to a staining procedure that
      only detects functional mitochondria. This method detects the in situ enzymatic
      activity of cytochrome C oxidase (COX), also known as Complex IV. Remarkably,
      cancer cells show an over-abundance of COX activity, while adjacent stromal cells
      remain essentially negative. Adjacent normal ductal epithelial cells also show
      little or no COX activity, relative to epithelial cancer cells. Thus, oxidative
      mitochondrial activity is selectively amplified in cancer cells. Although COX
      activity staining has never been applied to cancer tissues, it could now be used
      routinely to distinguish cancer cells from normal cells, and to establish
      negative margins during cancer surgery. Similar results were obtained with NADH
      activity staining, which measures Complex I activity, and succinate dehydrogenase
      (SDH) activity staining, which measures Complex II activity. COX and NADH
      activities were blocked by electron transport inhibitors, such as Metformin. This
      has mechanistic and clinical implications for using Metformin as an anti-cancer
      drug, both for cancer therapy and chemo-prevention. We also immuno-stained human
      breast cancers for a series of well-established protein biomarkers of metabolism.
      More specifically, we now show that cancer-associated fibroblasts over-express
      markers of autophagy (cathepsin B), mitophagy (BNIP3L), and aerobic glycolysis
      (MCT4). Conversely, epithelial cancer cells show the over-expression of a
      mitochondrial membrane marker (TOMM20), as well as key components of Complex IV
      (MT-CO1) and Complex II (SDH-B). We also validated our observations using a
      bioinformatics approach with data from > 2,000 breast cancer patients, which
      showed the transcriptional upregulation of mitochondrial oxidative
      phosphorylation (OXPHOS) in human breast tumors (p < 10(-20)), and a specific
      association with metastasis. Therefore, upregulation of OXPHOS in epithelial
      tumor cells is a common feature of human breast cancers. In summary, our data
      provide the first functional in vivo evidence that epithelial cancer cells
      perform enhanced mitochondrial oxidative phosphorylation, allowing them to
      produce high amounts of ATP. Thus, we believe that mitochondria are both the
      "powerhouse" and "Achilles' heel" of cancer cells.

PMID- 22134193
TI  - A mind "surrounded by a moat": a first-person account of cognitive impairment in
      multiple sclerosis.
AB  - This is a first-person account of the cognitive impairments--in speaking,
      writing, and thinking-caused by multiple sclerosis in a professional writer. The
      patient explains how she has worked around her deficits in rebuilding her life
      over the 18 years since her diagnosis. Her personal account is woven together
      with her clinical history, including her neuropsychological testing and magnetic
      resonance imaging results. A companion article giving perspectives on the case
      was written by a cognitive neuroscientist who has been studying some of the types
      of deficits reported by the patient.

PMID- 22134191
TI  - Beyond alcoholism: Wernicke-Korsakoff syndrome in patients with psychiatric
      disorders.
AB  - OBJECTIVE: Wernicke encephalopathy and Korsakoff syndrome (the combined disorder
      is named Wernicke-Korsakoff syndrome [WKS]) are preventable, life-threatening
      neuropsychiatric syndromes resulting from thiamine deficiency. WKS has
      historically been associated with alcoholism; more recently, it has been
      recognized in patients who have anorexia nervosa or have undergone bariatric
      surgery for obesity. However, patients with nutritional deficiencies of any
      origin are at risk for WKS. We present clinical histories and neuroimaging data
      on 2 young adults with underlying psychiatric disorders who became malnourished
      and developed WKS. METHODS: A young woman with bipolar disorder and somatization
      disorder was hospitalized for intractable vomiting. A young man with chronic
      paranoid schizophrenia developed delusions that food and water were harmful, and
      was hospitalized after subsisting for 4 months on soda pop. RESULTS: Acute, life
      threatening Wernicke encephalopathy was confirmed in both patients by brain
      magnetic resonance imaging showing classic thalamic injury. The patients were
      left with persistent cognitive and physical disabilities that were consistent
      with Korsakoff syndrome. CONCLUSIONS: Failure to suspect a vitamin deficiency led
      to permanent cognitive and physical disabilities that may necessitate lifelong
      care for these patients. The neuropsychiatric consequences could have been
      prevented by prompt recognition of their thiamine deficiency.

PMID- 22134194
TI  - Mixed hearing loss in iatrogenic tympanic membrane perforations over the round
      window niche and the immediate effect of paper patch myringoplasty.
AB  - OBJECTIVES: Report the immediate audiologic effect of paper patch myringoplasty
      to repair iatrogenic tympanic membrane perforations directly over the round
      window. METHODS: Retrospective case-control study of 15 patients treated for
      inner ear disease with a MicroWick and dexamethasone for 1 month, resulting in 2
      mm perforations over the round window. Paper patch myringoplasties were performed
      to repair the perforations. Audiograms were performed before and immediately
      after the paper patch myringoplasty. RESULTS: After paper patch placement, there
      was a significant improvement in air-bone gap at 250 (p < 0.001), 500 (p =
      0.003), and 1000 Hz (p = 0.004) and a significant improvement in bone conduction
      (BC) threshold at 250 (p = 0.002), 500 (p < 0.001), 1000 (p = 0.002), 2000 (p =
      0.003), and 3000 Hz (p = 0.02). CONCLUSIONS: Paper patch myringoplasty improves
      both air conduction and BC hearing from small perforations over the round window.
      The decrease in BC hearing is a result of middle ear mechanics and is not a true
      sensorineural hearing loss.

PMID- 22134196
TI  - Selective use of endoscopic ultrasound in the evaluation of carcinomas of the
      pancreatic head.
AB  - BACKGROUND: The aims of this study were to assess the role of endoscopic
      ultrasound (EUS) in the evaluation of adenocarcinoma of the head of the pancreas
      in cases of diagnostic dilemma and to determine the strength of agreement between
      perceived pre-operative stage as determined by computerised tomography (CT) and
      EUS and histopathological stage. METHODS: Patients undergoing pancreatic EUS were
      identified from a computerised radiology database. The strengths of agreement
      between the radiological and histopathological stages were determined by the
      weighted kappa (Kw) statistic. RESULTS: Fifty-eight patients were identified. Of
      37 patients with a pancreatic head mass on prior imaging, 32 had a diagnosis of
      adenocarcinoma confirmed by EUS, as did 11 of 21 patients with suspicious
      pancreatic head lesions. Twenty-five of 43 patients were deemed to have
      resectable carcinomas, and 2 patients had resectable mucinous lesions. In
      comparing CT and EUS in the 25 patients undergoing resection, the Kw for T and N
      stages was 0.250 (p = 0.05) and -0.080 (p = 0.288), respectively, for CT,
      compared with 0.738 (p = 0.0001) and 0.606 (p = 0.0001), respectively, for EUS.
      CONCLUSIONS: EUS was effective in assessing the resectability of pancreatic head
      adenocarcinomas. Furthermore, EUS held a significant 3-fold advantage over CT
      with regard to T stage and an even higher significant advantage with regard to N
      stage.

PMID- 22134197
TI  - The N-methyl-d-aspartic acid receptor antagonist memantine ameliorates and delays
      the development of arthritis by enhancing regulatory T cells.
AB  - The neuroendocrine impact on rheumatoid arthritis is not yet fully described
      although numerous neurotransmitters are shown to act as inflammatory modulators.
      One of these is the excitatory transmitter glutamate (Glu). In this study, the
      influence of the Glu receptor (GluR)-mediated effects on collagen-induced
      arthritis (CIA) was investigated. CIA was induced in DBA/1 mice by immunization
      with chicken collagen type II (CII). Mice were exposed to the following GluR
      antagonists: group 1, the N-methyl-D-aspartic acid (NMDA) receptor channel
      blocker memantine; group 2, the metabotropic GluR antagonist AIDA, and group 3,
      the excitatory amino acid receptor antagonist kynurenic acid (KA). Arthritis was
      evaluated clinically and histologically and compared to PBS-treated controls. The
      effects of treatment on T cell populations and the levels of anti-CII and anti
      citrullinated peptide antibodies were evaluated. Memantine treatment
      significantly improved the course of CIA, reducing synovitis (p = 0.007) and the
      frequency of erosions (p = 0.007). Memantine treatment up-regulated the
      expression of Foxp3 in spleen CD4+ T cells followed by an increase in CD4+CD25+
      regulatory T cells. The other GluR antagonists, AIDA and KA, had no effect on
      CIA. These results demonstrate that blockade of the NMDA receptor channel with
      memantine delays and attenuates the development of arthritis, probably by
      promoting the development of regulatory T lymphocytes.

PMID- 22134198
TI  - Intensity and duration of obesity-related counseling: association with 5-Year BMI
      trends among obese primary care patients.
AB  - We examined 5-year trends in BMI among obese primary care patients to determine
      whether obesity-related education such as nutrition counseling or a weight
      management program was associated with declines in BMI. Veterans with BMI >=30
      kg/m(2) and >=1 primary care visits in fiscal year 2002 were identified from the
      Veterans Health Administration's (VHA) national databases. Outpatient visits from
      fiscal year 2002-2006 for nutrition counseling, exercise, or weight management
      were grouped into five categories varying in intensity and duration: (i) intense
      and-sustained, (ii) intense-only, (iii) irregular, (iv) limited, and (v) no
      counseling. Generalized estimating equation assessed associations between obesity
      related counseling and BMI trend (annual rate of BMI change fiscal year 2002
      2006) among cohort members with complete race/ethnic data (N = 179,881).
      Multinomial logistic regression compared intensity and duration of counseling
      among patients whose net BMI increased or decreased by >=10% vs. remained stable.
      Compared with patients receiving "intense-and-sustained" counseling, the BMI
      trend of those receiving "intense-only" or "irregular" counseling was not
      significantly different, but patients receiving "no counseling" or "limited
      counseling" had significantly higher rates of decreasing BMI (-0.12 and -0.08 BMI
      per year; P < 0.01, respectively). This was especially true for veterans in their
      50-60s, compared with the oldest veterans who were most likely to lose weight. In
      contrast, younger veterans (18-35 years) were least likely to lose weight; their
      BMI tended to increase regardless of counseling intensity and duration. Enhanced
      efforts are needed to detect and combat increasing weight trajectories among
      veterans who are already obese, especially among those aged 18-35 who are at
      greatest risk.

PMID- 22134199
TI  - Validity of the Remote Food Photography Method (RFPM) for estimating energy and
      nutrient intake in near real-time.
AB  - Two studies are reported; a pilot study to demonstrate feasibility followed by a
      larger validity study. Study 1's objective was to test the effect of two
      ecological momentary assessment (EMA) approaches that varied in intensity on the
      validity/accuracy of estimating energy intake (EI) with the Remote Food
      Photography Method (RFPM) over 6 days in free-living conditions. When using the
      RFPM, Smartphones are used to capture images of food selection and plate waste
      and to send the images to a server for food intake estimation. Consistent with
      EMA, prompts are sent to the Smartphones reminding participants to capture food
      images. During Study 1, EI estimated with the RFPM and the gold standard, doubly
      labeled water (DLW), were compared. Participants were assigned to receive
      Standard EMA Prompts (n = 24) or Customized Prompts (n = 16) (the latter received
      more reminders delivered at personalized meal times). The RFPM differed
      significantly from DLW at estimating EI when Standard (mean +/- s.d. = -895 +/-
      770 kcal/day, P < 0.0001), but not Customized Prompts (-270 +/- 748 kcal/day, P =
      0.22) were used. Error (EI from the RFPM minus that from DLW) was significantly
      smaller with Customized vs. Standard Prompts. The objectives of Study 2 included
      testing the RFPM's ability to accurately estimate EI in free-living adults (N =
      50) over 6 days, and energy and nutrient intake in laboratory-based meals. The
      RFPM did not differ significantly from DLW at estimating free-living EI (-152 +/-
      694 kcal/day, P = 0.16). During laboratory-based meals, estimating energy and
      macronutrient intake with the RFPM did not differ significantly compared to
      directly weighed intake.

PMID- 22134200
TI  - Glucagon-like peptide-1 regulation of carbohydrate intake is differentially
      affected by obesogenic diets.
AB  - The incretin hormone glucagon-like peptide-1 (GLP-1) has been implicated in the
      regulation of appetite by acting as an anorexigenic gut-brain signal. The
      postprandial release of GLP-1 can be blunted in obese humans and animals.
      However, it remains unknown whether obesogenic diets with varying fat and
      carbohydrate content may differentially influence the effectiveness of GLP-1
      feedback. To investigate this, male Sprague-Dawley rats were fed a standard (low
      fat) chow diet, or one of two high-energy diets varying in fat content (45 or 60
      kcal%) for 28 weeks. Intake of sucrose and fructose solutions, two commonly added
      sugars in the Western diet, was then tested in nondeprived rats following
      administration of the GLP-1 receptor agonist, Exendin-4 (0, 0.5, 1, 2, 3 ug/kg;
      s.c.). Exendin-4 dose-dependently reduced short (2 h) sucrose and fructose
      intake. This effect was significantly attenuated in rats fed more dietary fat,
      despite both diets resulting in obesity. These findings demonstrate that intake
      of carbohydrates when offered as treats can be regulated by GLP-1 and suggests
      that dietary fat consumption, rather than extra calories or obesity, may lead to
      impaired GLP-1 feedback to curb carbohydrate intake. Future studies are warranted
      to investigate the relevance of these observations to humans and to elucidate the
      underlying mechanisms.

PMID- 22134201
TI  - Tissue distribution of S-(2-succino)cysteine (2SC), a biomarker of mitochondrial
      stress in obesity and diabetes.
AB  - S-(2-succino)cysteine (2SC) is a chemical modification of proteins produced by
      reaction of fumarate with thiol groups in protein, a process known as
      succination. We propose to use the name S-(2-succino)cysteine (instead of S-(2
      succinyl)cysteine) from this point on. This is to distinguish protein succination
      (in which fumarate forms a thioether linkage with cysteine residues) from
      succinylation (in which an ester, thioester or amide bond would be formed).
      Succination of proteins is increased in muscle of type 1 diabetic rats and in
      adipose tissue in type 2 diabetic mice. The increase in 2SC is a direct result of
      tissue accumulation of fumarate in response to nutrient excess and resultant
      mitochondrial stress in diabetes. In this study, we examine the breadth of
      succination of tissue proteins in the db/db type 2 model of diabetes. We also
      determined the extent of succination in epididymal adipocytes of type 1 (Akita,
      streptozotocin (STZ)) and type 2 (ob/ob, db/db) diabetic mice, in diet-induced
      obese (DIO) mice, and in the adipose tissue of ground squirrels in various stages
      of hibernation. While succination was not increased in most tissues (brain,
      heart, kidney, liver, skeletal muscle) in the db/db model of diabetes, it was
      increased in all adipose beds of type 2 diabetic and DIO mice in comparison to
      their controls. Succination was not increased in adipocytes of type 1 diabetic
      mice. Adipose tissue from hibernating (HIB) 13-lined ground squirrels was also
      studied to determine if obesity in the absence of hyperglycemia affected
      succination of proteins. There were no differences in succination of proteins in
      brown or white adipose tissue over the torpor-arousal cycle. We conclude that 2SC
      is a biomarker of nutrient excess and mitochondrial stress in adipose tissue,
      increasing under the hyperglycemic and insulin resistant conditions associated
      with type 2 diabetes and obesity.

PMID- 22134202
TI  - Bifunctional peptides that precisely biomineralize Au clusters and specifically
      stain cell nuclei.
AB  - A bifunctional peptide containing a domain that targets cell nuclei and a domain
      with the ability to biomineralize and capture Au clusters is presented. The
      peptide-Au clusters exhibit red emission (lambda(em) = 677 nm) and specifically
      stain the nuclei of three cell lines.

PMID- 22134203
TI  - The new AAOS clinical practice guidelines on venous thromboembolic prophylaxis:
      how to adapt them to your practice.

PMID- 22134204
TI  - "Growth friendly" spine surgery: management options for the young child with
      scoliosis.
AB  - The natural history of early onset scoliosis is dismal and associated with poor
      pulmonary function and increased mortality. Although limited in situ fusion may
      be appropriate for certain types of congenital scoliosis deformities, spinal
      deformity that affects young children often requires a "growth friendly" surgical
      approach that allows for curve control while maintaining growth of the spine and
      thorax. Growth-friendly surgical management of early onset scoliosis can follow a
      distraction-based (ie, growth rods, vertical expandable prosthetic titanium rib
      [Synthes, West Chester, PA]), guided-growth (ie, Luque trolley technique, Shilla
      technique), or compression-based (ie, tethers, staples) strategy.

PMID- 22134205
TI  - Iliotibial band syndrome: evaluation and management.
AB  - Iliotibial band syndrome is a common overuse injury typically seen in runners,
      cyclists, and military recruits. Affected patients report lateral knee pain
      associated with repetitive motion activities. The diagnosis is usually made based
      on a characteristic history and physical examination, with imaging studies
      reserved for cases of recalcitrant disease to rule out other pathologic entities.
      Several etiologies have been proposed for iliotibial band syndrome, including
      friction of the iliotibial band against the lateral femoral epicondyle,
      compression of the fat and connective tissue deep to the iliotibial band, and
      chronic inflammation of the iliotibial band bursa. The mainstay of treatment is
      nonsurgical; however, in persistent or chronic cases, surgical management is
      indicated.

PMID- 22134206
TI  - Total hip arthroplasty in the ankylosed hip.
AB  - Altered biomechanics secondary to hip ankylosis often result in degeneration of
      the lumbar spine, ipsilateral knee, and contralateral hip and knee. Symptoms in
      these joints may be reduced with conversion total hip arthroplasty (THA) of the
      ankylosed hip. THA in the ankylosed hip is a technically challenging procedure,
      and the overall clinical outcome is generally less satisfactory than routine THA
      performed for osteoarthritis and other etiologies. Functional integrity of the
      hip abductor muscles is the most important predictor of walking ability following
      conversion THA. Many patients experience persistent limp, and it can take up to 2
      years to fully assess final functional outcome. Risk factors cited for increased
      risk of failed THA include prior surgical ankylosis and age <50 years at the time
      of conversion THA.

PMID- 22134207
TI  - Dupuytren disease: an evolving understanding of an age-old disease.
AB  - Dupuytren disease, a clinical entity originally described more than 400 years
      ago, is a progressive disease of genetic origin. Excessive myofibroblast
      proliferation and altered collagen matrix composition lead to thickened and
      contracted palmar fascia; the resultant digital flexion contractures may severely
      limit function. The pathophysiology is multifactorial and remains a topic of
      research and debate. Genetic predisposition, trauma, inflammatory response,
      ischemia, and environment, as well as variable expression of proteins and growth
      factors within the local tissue, all play a role in the disease process. Common
      treatments of severe disease include open fasciectomy or fasciotomy. These
      procedures may be complicated by the complex anatomic relationships between cords
      (pathologic contracted fascia) and adjacent neurovascular structures. Recent
      advances in the management of Dupuytren disease involve less invasive treatments,
      such as percutaneous needle fasciotomy and injectable collagenase Clostridium
      histolyticum. Postoperative management focuses on minimizing the cellular
      response of cord disruption and maximizing range of motion through static or
      dynamic extension splinting.

PMID- 22134208
TI  - Management of multidirectional instability of the shoulder.
AB  - Multidirectional shoulder instability is defined as symptomatic instability in
      two or more directions. Instability occurs when static and dynamic shoulder
      stabilizers become incompetent due to congenital or acquired means. Nonspecific
      activity-related pain and decreased athletic performance are common presenting
      complaints. Clinical suspicion for instability is essential for timely diagnosis.
      Several examination techniques can be used to identify increased glenohumeral
      translation. It is critical to distinguish increased laxity from instability.
      Initial management begins with therapeutic rehabilitation. If surgical management
      is required, capsular plication has been used successfully. Advanced arthroscopic
      techniques offer several advantages over traditional open approaches and may have
      similar outcomes. The role of rotator interval capsular plication is
      controversial, but it may be used to augment capsular plication in patients with
      specific patterns of instability. Despite encouraging results, outcomes remain
      inferior to those associated with traumatic unidirectional instability.

PMID- 22134209
TI  - Preventing venous thromboembolic disease in patients undergoing elective hip and
      knee arthroplasty.
AB  - This guideline supersedes a prior one from 2007 on a similar topic. The work
      group evaluated the available literature concerning various aspects of patient
      screening, risk factor assessment, and prophylactic treatment against venous
      thromboembolic disease (VTED), as well as the use of postoperative mobilization,
      neuraxial agents, and vena cava filters. The group recommended further assessment
      of patients who have had a previous venous thromboembolism but not for other
      potential risk factors. Patients should be assessed for known bleeding disorders,
      such as hemophilia, and for the presence of active liver disease. Patients who
      are not at elevated risk of VTED or for bleeding should receive pharmacologic
      prophylaxis and mechanical compressive devices for the prevention of VTED. The
      group did not recommend specific pharmacologic agents and/or mechanical devices.
      The work group recommends, by consensus opinion, early mobilization for patients
      following elective hip and knee arthroplasty. The use of neuraxial anesthesia can
      help limit blood loss but was not found to affect the occurrence of VTED. No
      clear evidence was established regarding whether inferior vena cava filters can
      prevent pulmonary embolism in patients who have a contraindication to
      chemoprophylaxis and/or known VTED.

PMID- 22134210
TI  - AAOS clinical practice guideline: preventing venous thromboembolic disease in
      patients undergoing elective hip and knee arthroplasty.

PMID- 22134213
TI  - The influence of particle clustering on the rheological properties of highly
      concentrated magnetic nanofluids.
AB  - In this paper the particle volume fraction and temperature dependence of the
      dynamic viscosity of highly concentrated transformer oil based magnetic
      nanofluids was investigated in the absence of an external magnetic field. The
      solid particle volume fraction dependence of the relative viscosity was found to
      be very well fitted by the Krieger-Dougherty formula, whence the mean ellipticity
      of the colloidal particles and the effective surfactant layer thickness were
      obtained. Using the information on the particles' size and shape statistics
      obtained from TEM, DLS and magnetogranulometry investigations, it was concluded
      that the magnetite nanoparticles agglomerate in small clusters of about 1.3
      particles/cluster, due to the van der Waals interactions. The effective thickness
      of the oleic acid surfactant layer was estimated as about 1.4 nm, in very good
      agreement with the value resulted from previous SANS investigations.

PMID- 22134214
TI  - Self-assembling systems based on amphiphilic alkyltriphenylphosphonium bromides:
      elucidation of the role of head group.
AB  - A systematic study of the aggregation behavior of alkyltriphenylphosphonium
      bromides (TPPB-n; n=8, 10, 12, 14, 16, 18; here n is the number of carbon atoms
      in alkyl groups) in aqueous solutions has been carried out and compared with
      trimethyl ammonium bromides (TMAB-n). Critical micelle concentrations (cmcs) of
      TPPB-n and TMAB-n decrease with the number of carbon atoms with the slope
      parameter of ca.0.3. The low cmcs and effective solubilization power toward
      Orange OT indicate high micellization capacity of phosphonium surfactants. The
      low counterion binding parameter beta is revealed for TPPB-10 and TPPB-12, while
      high counterion binding of >=80% is observed for high TPPB-n homologs. Values of
      the surface potential psi calculated on the basis of pK(a) shifts of p
      nitrophenols is similar for both series and monotonously increase with alkyl
      chain length. Several points indicate non-monotonic changes within TPPB-n series.
      There are peculiarities of the tensiometry and solubilization plots for high
      homologs and above mentioned increases in counterion binding on transiting from
      low to high molecular weight surfactants. Differences in aggregation behavior
      between TPPB and TMAB series and between low and high homologs can be due to the
      specific structural character of the TPP(+) cation, which is supported by X-ray
      data.

PMID- 22134215
TI  - Nitrogen-rich porous covalent imine network (CIN) material as an efficient
      catalytic support for C-C coupling reactions.
AB  - In an effort to expand the realm of possibilities of nitrogen-rich porous
      materials that could be used in catalysis, herein we report the synthesis of a
      new highly nitrogen rich (ca. 45%) porous covalent imine network (CIN-1) material
      employing simple Schiff base chemistry and further grafting its surface with
      palladium. Pd-loaded CIN-1 support acts as a truly heterogeneous catalyst towards
      Suzuki C-C coupling reaction between aryl halides with arylboronic acids. High
      surface area and excellent accessibility of the catalytic sites make it very
      efficient for heterogeneous catalysis. The stability of the catalyst due to
      intimate contact between nitrogen-rich organic support and metal allows several
      reuses with only a minor loss in catalytic activity.

PMID- 22134216
TI  - Analyzing the metabolic stress response of recombinant Escherichia coli cultures
      expressing human interferon-beta in high cell density fed batch cultures using
      time course transcriptomic data.
AB  - Fed batch cultures expressing recombinant interferon beta under the T7 promoter
      were run with different exponential feeding rates of a complex substrate and
      induced at varying cell densities. Post-induction profiles of the specific
      product formation rates showed a strong dependence on the specific growth rate
      with the maximum product yield obtained at 0.2 h(-1). A study of the relative
      transcriptomic profiles as a function of pre-induction MU was therefore done to
      provide insight into the role of cellular physiology in enhancing recombinant
      protein expression. Hierarchical clustering analysis of the significantly
      regulated genes allowed us to identify biologically important groups of genes
      which fall under specific master regulators. The groups were: rpoH, ArcB, CreB,
      Lrp, RelA, Fis and Hfq. The response of these regulators, which exert a feedback
      control on the growth and product formation rates correlated well with the
      expression levels obtained. Thus at the optimum pre-induction MU, the alternative
      sigma factors and ribosomal machinery genes did not get depressed till the 6th
      hour post-induction unlike at other specific growth rates, demonstrating a
      critical role for the genes in sustaining recombinant protein expression.

PMID- 22134217
TI  - Clostridium difficile infection:  an update on epidemiology, risk factors, and
      therapeutic options.
AB  - PURPOSE OF REVIEW: The incidence and severity of Clostridium difficile infection
      (CDI) around the world has increased over the past 20 years due to the emergence
      of hypervirulent strains, increased use and misuse of antibiotics, and the
      increase of susceptible at-risk populations. Treatments currently available for
      CDI are inadequate to impede the increasing spread and virulence of the
      infection, avoid recurrence in chronic patients or prevent infection in at-risk
      populations. RECENT FINDINGS: New and promising evidence has been presented
      during the past year, focusing on two major points: preservation of gut
      microflora and optimization of immune response to CDI and toxins. SUMMARY: The
      review aims to summarize the most recent evidence available on the epidemiology,
      risk factors and treatment of CDI. New antibiotics with selected action on C.
      difficile and limited effect on microflora (fidaxomicin) and donor fecal
      transplantation seem to have a relevant efficacy in treating CDI and reducing its
      recurrence. The use of selected monoclonal antibodies directed against C.
      difficile toxins in addition to standard therapy is a new, promising approach for
      the treatment of recurrent cases. Vaccination could be an additional weapon
      against CDI. New robust data are needed before recommendations can be made to
      abandon current treatment based on vancomycin and metronidazole and move toward
      new frontiers.

PMID- 22134218
TI  - Advances in the surgical management of inflammatory bowel disease.
AB  - PURPOSE OF REVIEW: The principles of surgical management of inflammatory bowel
      disease (IBD) continue to evolve with advances in medical therapy, surgical
      technique, and minimally invasive operative technology. The purpose of this
      review is to highlight such advances in colorectal and anorectal surgery for IBD
      over the last year. RECENT FINDINGS: Treatment of ulcerative colitis and Crohn's
      disease remains challenging and relies on knowledge of both medical and surgical
      therapies. Recent data support shorter hospitalization prior to surgical
      intervention in patients with acute severe ulcerative colitis, laparoscopic
      surgical approaches when feasible, and ciprofloxacin as optimal therapy for
      pouchitis, when preventive therapy with probiotics is not successful. SUMMARY:
      The management of IBD remains complex and highly individualized. In severe cases,
      a combination of immunosuppression and surgical therapies may be required.
      However, the associated risks of complications make judgments about optimal
      treatment plans challenging.

PMID- 22134219
TI  - Large intestine.

PMID- 22134220
TI  - Colonoscopy:  new approaches to better outcomes.
AB  - PURPOSE OF REVIEW: Prevention of colorectal cancer relies on the detection and
      removal of colorectal neoplasia. Recent advances in mucosal imaging and
      inspection techniques have increased the detection of small and diminutive
      colorectal polyps with unknown clinical impact. The ability to accurately predict
      whether a polyp is neoplastic may allow for an optical triage approach to polyp
      management, improving efficiency while reducing the cost and risk of polypectomy.
      RECENT FINDINGS: High-definition white light colonoscopy, cap-fitted colonoscopy,
      and dye-based pan-chromoendoscopy have each shown to increase polyp detection.
      Virtual chromoendoscopy, although not beneficial for polyp detection, allows for
      accurate in-vivo prediction of polyp pathology. Endoscopists' behaviors,
      independent of patient factors, strongly influence adenoma detection. Training
      methods focused on the techniques of high adenoma detectors also increase adenoma
      and polyp detection. SUMMARY: Advances in mucosal imaging and improvements in
      inspection technique have allowed us to detect more polyps and to predict their
      pathology with greater accuracy. An optical triage approach to either 'diagnose
      and discard' or 'diagnose and leave behind' has the potential to reduce the risk
      and cost of polypectomy.

PMID- 22134221
TI  - Subclinical micronutrient deficiency:  a problem in recognition.

PMID- 22134223
TI  - Food allergy:  a glimpse into the inner workings of gut immunology.
AB  - PURPOSE OF REVIEW: How food protein becomes recognized as an allergen remains a
      fundamental question. Previous studies indicated that the pathophysiology of food
      allergy is because of a skewed Th2 response to specific food glycoproteins. The
      focus has now shifted to understanding how a failure of regulatory mechanisms
      results in food allergy. This review summarizes the recent findings elucidating
      the small intestine's role in the pathophysiology of food allergy and the immune
      mechanisms of oral tolerance. RECENT FINDINGS: Gut homeostasis and immunity occur
      via a complex interplay of innate and adaptive immune responses. Immune exclusion
      is performed mainly by secretory IgA, although there are back-up mechanisms in
      place to induce oral tolerance when secretory IgA is lacking. Oral tolerance
      cannot occur in murine models lacking T regulatory cells, for which Foxp3+ is a
      key marker. Migration of Foxp3+ T cells from the mesenteric lymph nodes (MLNs) to
      the lamina propria occurs via gut-homing signals. Also in the MLNs are CD103+
      dendritic cells, which drive the differentiation of Foxp3+ T cells in the
      presence of TGF-beta and retinoic acid produced from dietary vitamin A. Lastly,
      microenvironmental signals from the microbiome can serve to enhance these
      interactions. SUMMARY: We have focused primarily on local immunologic variables
      that may affect the induction of oral tolerance in the gut and the mechanisms
      elucidated in animal models. However, many other variables such as genetics,
      commensal microbiota, and diet are likely to be important factors.

PMID- 22134222
TI  - Choline metabolism provides novel insights into nonalcoholic fatty liver disease
      and its progression.
AB  - PURPOSE OF REVIEW: Choline is an essential nutrient and the liver is a central
      organ responsible for choline metabolism. Hepatosteatosis and liver cell death
      occur when humans are deprived of choline. In the last few years, there have been
      significant advances in our understanding of the mechanisms that influence
      choline requirements in humans and in our understanding of choline's effects on
      liver function. These advances are useful in elucidating why nonalcoholic fatty
      liver disease (NAFLD) occurs and progresses sometimes to hepatocarcinogenesis.
      RECENT FINDINGS: Humans eating low-choline diets develop fatty liver and liver
      damage. This dietary requirement for choline is modulated by estrogen and by
      single-nucleotide polymorphisms in specific genes of choline and folate
      metabolism. The spectrum of choline's effects on liver range from steatosis to
      development of hepatocarcinomas, and several mechanisms for these effects have
      been identified. They include abnormal phospholipid synthesis, defects in
      lipoprotein secretion, oxidative damage caused by mitochondrial dysfunction, and
      endoplasmic reticulum stress. Furthermore, the hepatic steatosis phenotype can be
      characterized more fully via metabolomic signatures and is influenced by the gut
      microbiome. Importantly, the intricate connection between liver function, one
      carbon metabolism, and energy metabolism is just beginning to be elucidated.
      SUMMARY: Choline influences liver function, and the dietary requirement for this
      nutrient varies depending on an individual's genotype and estrogen status.
      Understanding these individual differences is important for gastroenterologists
      seeking to understand why some individuals develop NAFLD and others do not, and
      why some patients tolerate total parenteral nutrition and others develop liver
      dysfunction.

PMID- 22134224
TI  - Risk factors associated with cardiovascular morbidity and mortality in Spanish
      incident hemodialysis patients: two-year results from the ANSWER study.
AB  - AIMS: To identify factors associated with cardiovascular (CV) disease in
      hemodialysis. METHODS: Multicenter, prospective, 2-year, observational study in
      2,310 incident patients (3,496 patient-years). Multivariate Cox models determined
      baseline characteristics associated with CV disease. RESULTS: Main factors
      associated with CV deaths (6.3/100 patient-years) were: high Charlson score
      (hazard ratio (HR) 3.6; 95% confidence interval (CI) 1.7-7.5 for >=9 vs. <=4);
      low Karnofsky score (KS; HR 2.2; 95% CI 1.5-3.3 for KS <=50 vs. >70); female
      gender (HR 1.4; 95% CI 1.1-1.9); catheter access (HR 1.4; 95% CI 1.0-1.9); low
      (<3.5 g/dl) albumin (HR 2.5; 95% CI 1.8-3.3); ferritin deficiency (HR 1.6; 95% CI
      1.2-2.2 for <100 vs. >=100-500 ng/ml) and low body mass index (BMI; HR 1.9; 95%
      CI 1.2-3.0 for <20 vs. 20-25). A BMI of >=30 was a protective factor (HR 0.6; 95%
      CI 0.4-0.9). CONCLUSIONS: There is a high CV risk, especially in older patients
      with high comorbidity, low BMI, low albumin or iron deficiency. Catheter access
      increases the CV death risk.

PMID- 22134225
TI  - FLAMEnGO: a fuzzy logic approach for methyl group assignment using NOESY and
      paramagnetic relaxation enhancement data.
AB  - Building on a recent method by Matthews and co-workers [1], we developed a new
      and efficient algorithm to assign methyl resonances from sparse and ambiguous NMR
      data. The new algorithm (FLAMEnGO: Fuzzy Logic Assignment of MEthyl GrOups) uses
      Monte Carlo sampling in conjunction with fuzzy logic to obtain the assignment of
      methyl resonances at high fidelity. Furthermore, we demonstrate that the
      inclusion of paramagnetic relaxation enhancement (PRE) data in the assignment
      strategy increases the percentage of correct assignments with sparse NOE data.
      Using synthetic tests and experimental data we show that this new approach
      provides up to ~80% correct assignments with only 30% of methyl-methyl NOE data.
      In the experimental case of ubiquitin, PRE data from two spin labeled sites
      improve the percentage of assigned methyl groups up to ~91%. This new strategy
      promises to further expand methyl group NMR spectroscopy to very large
      macromolecular systems.

PMID- 22134226
TI  - An integration of vibration and cold relieves venipuncture pain in a pediatric
      emergency department.
AB  - OBJECTIVE: A randomized controlled trial compared a reusable device combining
      cold and vibration to standard care for pediatric venous access pain relief.
      METHODS: Pediatric emergency department patients received either the cold
      vibration device placed 5 to 10 cm proximally throughout venipuncture or standard
      care control (primarily vapocoolant spray). Block randomization of patients with
      or without lidocaine cream already in place ensured equal allocation in both
      intervention groups. Pain was measured via self- and parent-report using the 0-
      to 10-point Faces Pain Scale-Revised and with coded videotaped observed
      behaviors. Venipuncture success, use of distraction, and access times were also
      assessed. RESULTS: Eighty-one 4- to 18-year-olds were randomized to the device (n
      = 41) or standard care (n = 40) (median age, 10.09 years; 95% confidence interval
      [95% CI], 8.91-10.89). Median patient-reported pain scores with the device were
      lower than with standard care (-2; 95% CI, -4 to 0), as were parent-assessed pain
      scores (-2; 95% CI, -4 to -2). Observed distress behaviors were more common with
      standard care (2; 95% CI, 1-3) than with the device (1; 95% CI, 0-2).
      Venipuncture success was more likely with the device (odds ratio, 3.05; 95% CI,
      1.03-9.02). There were no device refusals. CONCLUSIONS: The combination of cold
      and vibration decreased venipuncture pain significantly more than standard care
      without compromising procedural success. A device incorporating these elements
      could overcome the common barriers to needle procedure pain control.

PMID- 22134227
TI  - Safety of high-concentration nitrous oxide by nasal mask for pediatric procedural
      sedation: experience with 7802 cases.
AB  - OBJECTIVES: Nitrous oxide is an effective sedative/analgesic for mildly to
      moderately painful pediatric procedures. This study evaluated the safety of
      nitrous oxide administered at high concentration (up to 70%) for procedural
      sedation. METHODS: This prospective, observational study included all patients
      younger than 18 years who received nitrous oxide for diagnostic or therapeutic
      procedures at a metropolitan children's facility. Patients' age, highest
      concentration and total duration of nitrous oxide administration, and adverse
      events were recorded. RESULTS: Nitrous oxide was administered on 7802 occasions
      to 5779 patients ranging in age from 33 days to 18 years (median, 5.0 years)
      during the 5.5-year study period. No adverse events were recorded for 95.7% of
      cases. Minor adverse events included nausea (1.6%), vomiting (2.2%), and
      diaphoresis (0.4%). Nine patients had potentially serious events, all of which
      resolved without incident. There was no difference in adverse event rates between
      nitrous oxide less than or equal to 50% and greater than 50% (P = 0.18). Patients
      aged 1 to 4 years had the lowest adverse event rate (P < 0.001), with no
      difference between groups younger than 1 year, 5 to 10 years, and 11 to 18 years.
      Compared with patients with less than 15 minutes of nitrous oxide administration,
      patients with 15 to 30 minutes or more than 30 minutes of nitrous oxide
      administration were 4.2 (95% confidence interval, 3.2-5.4) or 4.9 (95% confidence
      interval, 2.6-9.3) times more likely to have adverse events. CONCLUSIONS: Nitrous
      oxide can be safely administered at up to 70% concentration by nasal mask for
      pediatric procedural sedation, particularly for short (<15 minutes) procedures.
      Nitrous oxide seems safe for children of all ages.

PMID- 22134228
TI  - Safety and efficacy of milk and molasses enemas compared with sodium phosphate
      enemas for the treatment of constipation in a pediatric emergency department.
AB  - OBJECTIVES: The purpose of this study was to determine the safety and efficacy of
      routine milk and molasses enemas (MME) compared with sodium phosphate enemas for
      the treatment of constipation in the pediatric emergency department (ED). A
      secondary objective included the identification of factors associated with enema
      selection in the pediatric ED. METHODS: This study was approved by the University
      of Texas Southwestern Medical Center Institutional Review Board. The study design
      was a retrospective comparative chart review. Medical records of patients who
      presented to the ED and received either MME or sodium phosphate enema for
      constipation between November 1, 2007, and November 1, 2008, were identified and
      reviewed for data collection. The following data were collected to determine
      safety and efficacy: baseline demographics, chief complaint, medical history,
      radiographic imaging, enema type, treatment dose, adverse effects, improvement in
      symptoms, time until defecation, failure of initial therapy requiring additional
      intervention, and time from treatment until disposition. RESULTS: Both treatment
      groups had similar baseline characteristics. No statistically significant
      differences in treatment effect were noted between MME and sodium phosphate
      enemas. Several clinically significant trends were noted including the need for
      additional rectal treatment after administration of sodium phosphate enemas
      versus oral therapy after MME. In addition, there were 6 cases of treatment
      failure with sodium phosphate enemas versus 1 case with MME. CONCLUSIONS: No
      statistically significant differences were found between MME and sodium phosphate
      enemas. Based on our results, the 2 treatment options were found to be equally
      safe and effective.

PMID- 22134229
TI  - Pediatric educational needs assessment for urban and rural emergency medical
      technicians.
AB  - OBJECTIVE: The objective of the study was to identify past experiences, present
      needs, barriers, and desired methods of training for urban and rural emergency
      medical technicians. METHODS: This 62-question pilot-tested written survey was
      administered at the 2008 Oregon EMS and 2009 EMS for Children conferences.
      Respondents were compared with registration lists and the state emergency medical
      services (EMS) database to assess for nonresponder bias. Agencies more than 10
      miles from a population of 40,000 were defined as rural. RESULTS: Two hundred
      nineteen (70%) of 313 EMS personnel returned the surveys. Respondents were 3%
      first responders, 27% emergency medical technician basics, 20% intermediates, and
      47% paramedics. Sixty-eight percent were rural, and 32% were urban. Sixty-eight
      percent reported fewer than 10% pediatric transports. Overall, respondents rated
      their comfort caring for pediatric patients as 3.1 on a 5-point Likert scale (95%
      confidence interval, 3.1-3.2). Seventy-two percent reported a mean rating of less
      than "comfortable" (4 on the scale) across 17 topics in pediatric care, which did
      not differ by certification level. Seven percent reported no pediatric training
      in the last 2 years, and 76% desired more. The "quality of available trainings"
      was ranked as the most important barrier to training; 26% of rural versus 7% of
      urban EMS personnel ranked distance as the most significant barrier (P < 0.01).
      Fifty-one percent identified highly realistic simulations as the method that
      helped them learn best. In the past 2 years, 19% had trained on a highly
      realistic pediatric simulator. One to 3 hours was the preferred duration for
      trainings. CONCLUSIONS: Except for distance as a barrier, there were no
      significant differences between urban and rural responses. Both urban and rural
      providers desire resources, in particular, highly realistic simulation, to
      address the infrequency of pediatric transports and limited training.

PMID- 22134230
TI  - Return visits to the emergency department among febrile children 3 to 36 months
      of age.
AB  - OBJECTIVES AND METHODS: The aim of the present retrospective, cross-sectional,
      descriptive study was to determine the characteristics of febrile 3- to 36-month
      old children who were admitted to the emergency department (ED) with the chief
      complaint of fever and returned with the same complaint within 72 hours
      (returning group), compared with age-matched children who did not return to the
      ED (nonreturning group). Demographics and predischarge evaluation extent were
      focused on. RESULTS: Compared with the nonreturning group (n = 305), the
      returning group (n = 92) demonstrated higher mean temperature at home (P =
      0.008), longer fever duration (P < 0.0001), and greater pain frequency (P =
      0.03). Demographics and predischarge evaluation extent were similar in both
      groups. Within the returning group, fever duration was longer at the time of the
      second visit (P = 0.004). CONCLUSIONS: Higher fever causes higher rate of return
      visits. Among the investigated groups, pain was the sole differentiating symptom.
      Further studies should identify patterns that diminish children's ED readmission.

PMID- 22134231
TI  - The association between crowding and mortality in admitted pediatric patients
      from mixed adult-pediatric emergency departments in Korea.
AB  - OBJECTIVE: We aimed to investigate the effect of crowding on the hospital
      mortality of pediatric patients from adult-pediatric mixed emergency departments
      (EDs). METHODS: We used the National Emergency Department Information System
      database, which included demographic, clinical, diagnostic, and procedural
      information with all emergency patients visiting to 116 EDs from Korea since
      2004. We enrolled EDs with mean length of stay of more than 6 hours. Study period
      was from January 2006 to December 2008. Pediatric patients younger than 15 years
      admitted from these EDs were study targets. We calculated the mean patient volume
      (mean number of patients in the ED) over 8-hour shift for each hospital. When the
      volume reached the highest quartile, the period was considered as crowded.
      Patients who came during the overcrowded period were defined as the crowded
      group. We performed a Kaplan-Meier analysis, and hazard ratio and 95% confidence
      intervals (95% CIs) were calculated using a Cox proportional hazards regression
      model. RESULTS: A total of 34 EDs and 125,031 admitted pediatric patients were
      included; 74,152 (59.3%) were male, and the mean age was 3.84 (95% CI, 3.82-3.86)
      years; 35,924 (28.7%) were determined as the crowded group. The 30-day mortality
      rates were 0.4% and 0.3% (P = 0.063) for the crowded group and for the noncrowded
      group, respectively. The hazard ratio for hospital mortality of the crowded group
      was 1.230 (95% CI, 1.019-1.558). CONCLUSIONS: The ED crowding was associated with
      increased hazard for hospital mortality for pediatric patients in mixed EDs.

PMID- 22134232
TI  - Remember the saphenous: ultrasound evaluation and intravenous site selection of
      peripheral veins in young children.
AB  - OBJECTIVES: The primary objective of this study was to measure the width and
      depth of peripheral veins using bedside ultrasound in children younger than 3
      years. Secondary objectives included the evaluation of other vein and patient
      characteristics that may affect intravenous (IV) site selection. Assessment of
      nursing preferences for peripheral IV site selection was performed. METHODS:
      Sixty children aged 0 to 3 years who presented to an urban pediatric emergency
      department were enrolled. Ultrasound measurements of the transverse diameter
      (width) and distance from the top of the vein to the skin (depth) were recorded.
      Upon examination, veins were categorized as visible, palpable, detectable only by
      ultrasound, or not detectable. Sixteen staff nurses rated the likelihood of
      successful IV placement among different peripheral veins. RESULTS: The mean width
      of saphenous veins was significantly larger than that of hand veins (2.8 vs 1.8
      mm, P < 0.0001). When comparing saphenous veins to antecubital veins, no
      significant difference was measured between the mean width (2.8 vs 2.8 mm). The
      mean depth of saphenous veins was significantly greater than those of hand veins
      (1.9 vs 1.4 mm, P < 0.0001) and antecubital veins (1.9 vs 1.6 mm, P = 0.019).
      Differences in visibility and palpability were observed between different vein
      types. Hand veins and antecubital veins were rated by the nursing staff as the
      most likely sites for successful IV placement, whereas saphenous veins were among
      the least likely (P < 0.0001). CONCLUSIONS: In children younger than 3 years, the
      saphenous vein is larger than hand veins and is similar in size to antecubital
      veins, although marginal differences in depth exist. The sonographic findings of
      the saphenous vein and antecubital vein suggest that either should be considered
      a superior first choice for IV cannulation in this age group. Knowledge of these
      differences is important when choosing a site for peripheral IV placement. Future
      studies should evaluate peripheral IV success rates by vein type with or without
      ultrasound guidance.

PMID- 22134233
TI  - Utility of laboratory tests for children in the emergency department with a first
      seizure.
AB  - OBJECTIVE: The objective of the study was to evaluate the factors associated with
      abnormal laboratory findings in patients visiting the emergency department (ED)
      after having their first seizure. METHODS: We included ED patients with first
      seizures and divided them into groups based on normal and abnormal laboratory
      results for serum levels of sodium, potassium, calcium, and glucose. We evaluated
      the differences in age, sex, the presence of fever, the presence of
      gastrointestinal symptoms, the duration and pattern of the seizure, and whether
      the seizure was still present at the ED. RESULTS: We evaluated 240 patients.
      Among them, abnormalities were found in 83 (34.8%) of 238 for serum sodium, 16
      (6.7%) of 238 for potassium, 11 (6.2%) of 177 for calcium, and 121 (52.3%) of 231
      for glucose. In the serum sodium and calcium group, no differences in associated
      factors between patients with and without abnormal laboratory results were found.
      However, results revealed differences in seizure duration between patients with
      and without abnormal laboratory glucose results (P = 0.005) and in age between
      patients with normal and abnormal potassium results (P = 0.002). CONCLUSIONS:
      There was no significant association among the factors of sex, fever,
      gastrointestinal symptoms, seizure duration, and seizures in patients who came to
      the ED with electrolyte abnormalities after a first seizure. However, glucose
      level abnormalities may have an association with increased seizure duration. We
      still do not have any suggestions as to which associated factors should be
      considered when doing common blood examinations in these patients.

PMID- 22134234
TI  - The seasonality of testicular torsion.
AB  - OBJECTIVE: Previous studies of the seasonality of testicular torsion have yielded
      conflicting results. Our goal was to examine this issue in a large emergency
      department (ED) database. We also hypothesized that seasonal patterns would be
      similar in younger and older patients. METHODS: This was a retrospective cohort
      of ED visits. This study was performed on 20 New Jersey and New York EDs. The
      subjects are consecutive patients seen by ED physicians from January 1, 1996, to
      December 31, 2009. The authors identified visits with testicular torsion using
      International Classification of Disease, Ninth Revision codes. We then determined
      the number of testicular torsion visits by month, correcting for the total number
      of days over the study period in each month. We compared the corrected number of
      visits for the winter (December-February) compared with the summer (June-August)
      using the Student t test, with alpha set at 0.05. We also calculated these visits
      for the older and younger half of the patients. Finally, we determined the
      correlation between mean monthly testicular torsion visits and ambient
      temperatures. RESULTS: Of the 8,545,979 visits in the database, 768 (0.009%) had
      an ED diagnosis of testicular torsion. The median age was 15.5 years
      (interquartile range, 11.7-20.8 years). We found that testicular torsion visits
      were 39% (95% confidence interval, 24%-57%) more likely in the winter compared
      with the summer, and this was similar when the older and younger half of the
      patients were analyzed separately. The correlation coefficient between mean
      monthly testicular torsion visits and ambient temperature was r = 0.54 (P =
      0.006). CONCLUSIONS: Testicular torsion visits are more frequent in the winter
      than in the summer months.

PMID- 22134235
TI  - Should a near-patient test be part of the management of pharyngitis in the
      pediatric emergency department?
AB  - OBJECTIVE: The study's objective was to evaluate the efficacy of a rapid
      streptococcal test as a single diagnostic agent in the diagnosis of streptococcal
      pharyngitis in patients presenting to a pediatric emergency department. METHODS:
      We performed a rapid streptococcal test as part of the diagnostic workup for
      patients presenting with clinical findings consistent with streptococcal
      pharyngitis. In addition to undergoing the study intervention, each patient had a
      standard throat swab sent to the laboratory for formal culture. A questionnaire
      detailing the clinical features was to be completed in each case. RESULTS: Two
      hundred ten near-patient tests were performed. Complete laboratory results were
      available in 177 cases (77%). Clinical data were available for analysis in 94
      patients (53%). In our patient population, the near-patient test had a high
      specificity (98.6%) but a low sensitivity (71%). The clinical presentation of
      confirmed group A beta-hemolytic streptococcal pharyngitis is very variable.
      CONCLUSIONS: The QuickVue In-Line Strep A test for streptococcal pharyngitis is
      unreliable in our patient population. Clinical findings are unhelpful in
      confirming the diagnosis. Formal laboratory culture is the criterion standard for
      identifying the organism, but the results are not clinically significant in every
      case. Acute pharyngitis presenting to the pediatric emergency department can be
      managed in accordance with the recommendations in the Scottish Intercollegiate
      Guideline Network guideline.

PMID- 22134236
TI  - Three-percent saline administration during pediatric critical care transport.
AB  - OBJECTIVES: The purpose of this study was to describe the administration of 3%
      saline (3%S) during pediatric critical care transport. METHODS: A retrospective
      study was performed on pediatric patients who underwent critical transport to
      Loma Linda University Children's Hospital from January 1, 2003, to June 30, 2007,
      and were given 3%S. Patients' demographics, admission diagnosis, route and amount
      of 3%S administration, serum electrolytes, vital signs, radiographic data, and
      Glasgow Coma Scale scores were collected and analyzed. RESULTS: A total of 101
      children who received 3%S infusions during pediatric critical care transport were
      identified. Mean patient age was 5.9 years, and mean patient weight was 27.6 kg.
      The main indications for infusing 3%S were suspected cerebral edema (41%),
      intracranial bleed with edema (51%), and symptomatic hyponatremia (6%). The
      amount of 3%S bolus ranged from 1.2 to 24 mL/kg, with a mean of 5.4 mL/kg. Serum
      electrolytes before and after 3%S infusion demonstrated significant increases in
      sodium, chloride, and bicarbonate levels (P < 0.05). A significant reduction was
      also seen in serum urea nitrogen levels and anion gap. Radiographic imaging
      performed before 3%S infusion demonstrated findings consistent with concerns of
      increased intracranial pressure such as intracranial bleed and cerebral edema.
      The route of initial 3%S infusions was mainly through peripheral intravenous
      lines (96%). No complications related to the 3%S delivery such as local
      reactions, renal abnormalities, or central pontine myelinolysis were observed.
      CONCLUSIONS: It seems 3%S may be administered safely during pediatric critical
      transport and administration routes can include peripheral lines. With the
      importance of initiating therapy early to improve patient outcomes, the use of
      3%S may benefit transported children with brain injury and suspected intracranial
      hypertension.

PMID- 22134238
TI  - Mutant p53 oncogenic functions are sustained by Plk2 kinase through an
      autoregulatory feedback loop.
AB  - Aberrant activation of kinases has emerged to be a key event along with tumor
      progression, maintenance of tumor phenotype and response to anticancer
      treatments. This study documents the existence of an oncogenic auto-regulatory
      feedback loop that includes the Polo-like kinase-2 (Snk/Plk2) and mutant p53
      proteins. Plk2 protein binds to and phosphorylates mutant p53, thereby
      potentiating its oncogenic activities. Phosphorylated mutant p53 binds more
      efficiently to p300 consequently strengthening its own transcriptional activity.
      Plk2 gene is regulated at a transcriptional level by both wt- and mutant p53
      proteins. This leads to growth suppression or enhanced cell proliferation and
      chemo-resistance, respectively. In turn, the siRNA-mediated knock down of either
      mutant p53 or Plk2 proteins significantly curtails the growth properties of tumor
      cells and their chemo-resistance to anticancer treatments. Therefore, this paper
      identifies a novel tumor network including Plk2 and mutant p53 proteins whose
      triggering in response to DNA damage might disclose important implications for
      the treatment of human cancers.

PMID- 22134239
TI  - Oxygen sensing is impaired in ATM-defective cells.
AB  - The transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) is a master
      regulator of cell adaptation to decreasing oxygen levels. High oxygen tension
      promotes proteosomal degradation of HIF-1alpha via a pathway that requires
      hydroxylation of prolines 402 and 564. Low oxygen tension, hypoxia, inactivates
      the hydroxylases responsible for these modifications through a mechanism that is
      not fully understood but appears to require mitochondrial respiration and
      production of reactive oxygen species, ROS. Cells from individuals affected by
      ataxia telangiectasia syndrome have an impaired mitochondrial activity and a
      constitutive oxidative stress. Here we show that, in these cells, HIF-1alpha is
      efficiently degraded even in condition of low oxygen tension. Mechanistically
      this depends from a blunted increase in intracellular concentration of ROS in
      response to hypoxia which in turn is due to an increased cellular capacity of
      buffering ROS. We suggest that regulation of HIF-1alpha stability may depend on
      fold change of ROS relative to the basal level more than on their absolute value.
      Since elevated oxidative stress is a hallmark of many human disorders our finding
      may be relevant to different pathologies.

PMID- 22134240
TI  - p53 regulation: teamwork between RING domains of Mdm2 and MdmX.
AB  - p53 is a major tumor suppressor frequently inactivated through direct gene
      mutation and alternative mechanisms including overexpression of Mdm2 and MdmX.
      Both Mdm2 and MdmX are essential for negative regulation of p53 in vivo in a
      mutually dependent manner. The RING domain dependent E3 ligase activity of Mdm2
      has been shown to be essential for negative regulation of p53. The prevailing
      model has dubbed MdmX as an inhibitor of p53 transcriptional activity through
      direct binding of its N-terminal domain to p53. However, recent findings
      established an essential role of the RING domain of MdmX in p53 degradation in
      vitro and in vivo. Biochemically, Mdm2 on its own is a monoubiquitinatuion E3
      ligase, however, MdmX can convert Mdm2 into a polyubiquitination E3 ligase
      necessary for p53 proteasomal degradation in cells, through their RING-RING
      interactions. While Mdm2 is the catalytic components of Mdm2/MdmX E3 complex,
      MdmX is both the activating component and a substrate of the holoenzyme. Knock-in
      of RING mutant MdmX in mice causes p53-dependent embryonic lethality in a similar
      manner as knockout of MdmX whole gene. The new advance of the field assigned an
      essential role of the RING domain of MdmX in negative regulation of p53 in vivo,
      just like Mdm2 RING domain, through p53 degradation.

PMID- 22134241
TI  - Selective radiosensitization of p53 mutant pancreatic cancer cells by combined
      inhibition of Chk1 and PARP1.
AB  - We have recently shown that inhibition of HRR (homologous recombination repair)
      by Chk1 (checkpoint kinase 1) inhibition radiosensitizes pancreatic cancer cells
      and others have demonstrated that Chk1 inhibition selectively sensitizes p53
      mutant tumor cells. Furthermore, PARP1 [poly (ADP-ribose) polymerase-1]
      inhibitors dramatically radiosensitize cells with DNA double strand break repair
      defects. Thus, we hypothesized that inhibition of HRR (mediated by Chk1 via
      AZD7762) and PARP1 [via olaparib (AZD2281)] would selectively sensitize p53
      mutant pancreatic cancer cells to radiation. We also used 2 isogenic p53 cell
      models to assess the role of p53 status in cancer cells and intestinal epithelial
      cells to assess overall cancer specificity. DNA damage response and repair were
      assessed by flow cytometry, gammaH2AX, and an HRR reporter assay. We found that
      the combination of AZD7762 and olaparib produced significant radiosensitization
      in p53 mutant pancreatic cancer cells and in all of the isogenic cancer cell
      lines. The magnitude of radiosensitization by AZD7762 and olaparib was greater in
      p53 mutant cells compared with p53 wild type cells. Importantly, normal
      intestinal epithelial cells were not radiosensitized. The combination of AZD7762
      and olaparib caused G 2 checkpoint abrogation, inhibition of HRR, and persistent
      DNA damage responses. These findings demonstrate that the combination of Chk1 and
      PARP1 inhibition selectively radiosensitizes p53 mutant pancreatic cancer cells.
      Furthermore, these studies suggest that inhibition of HRR by Chk1 inhibitors may
      be a useful strategy for selectively inducing a BRCA1/2 'deficient-like'
      phenotype in p53 mutant tumor cells, while sparing normal tissue.

PMID- 22134242
TI  - Involvement of the nuclear proteasome activator PA28gamma in the cellular
      response to DNA double-strand breaks.
AB  - The DNA damage response (DDR) is a complex signaling network that leads to damage
      repair while modulating numerous cellular processes. DNA double-strand breaks
      (DSBs), a highly cytotoxic DNA lesion, activate this system most vigorously. The
      DSB response network is orchestrated by the ATM protein kinase, which
      phosphorylates key players in its various branches. Proteasome-mediated protein
      degradation plays an important role in the proteome dynamics following DNA damage
      induction. Here, we identify the nuclear proteasome activator PA28gamma
      (REGgamma; PSME3) as a novel DDR player. PA28gamma depletion leads to cellular
      radiomimetic sensitivity and a marked delay in DSB repair. Specifically,
      PA28gamma deficiency abrogates the balance between the two major DSB repair
      pathways--nonhomologous end-joining and homologous recombination repair.
      Furthermore, PA28gamma is found to be an ATM target, being recruited to the DNA
      damage sites and required for rapid accumulation of proteasomes at these sites.
      Our data reveal a novel ATM-PA28gamma-proteasome axis of the DDR that is required
      for timely coordination of DSB repair.

PMID- 22134243
TI  - Low-dose Hsp90 inhibitors tumor-selectively sensitize bladder cancer cells to
      chemoradiotherapy.
AB  - Although radical cystectomy with urinary diversion is the standard treatment for
      muscle-invasive bladder cancer (MIBC), loss of native bladder frequently impairs
      patient's quality of life (QOL). Bladder-sparing approach incorporating
      chemoradiotherapy (CRT) improves QOL while not compromising survival outcomes in
      MIBC patients. In this approach, complete response to induction CRT is a
      prerequisite for bladder preservation and favorable oncological outcomes. We
      investigated a strategy to potentiate CRT response of bladder cancer cells by
      using Hsp90 inhibitors in preclinical models. Hsp90 inhibitors at low
      concentrations, which did not exert cytocidal effects but inactivated key anti
      apoptotic proteins including erbB2, Akt, and NF-kappaB, efficiently sensitized
      bladder cancer cells (T24, 5637 and UM-UC-3 cells) to in vitro CRT by enhancing
      apoptosis. Importantly, the sensitizing effects were not observed in primarily
      cultured normal human urothelial cells. We also showed that CRT induces
      accumulation of nuclear phospho-Akt, which antagonizes apoptosis, and that Hsp90
      inhibitors block the cellular process. Hsp90 inhibition sensitized bladder cancer
      cells to in vitro CRT more effectively than sole or combined inhibition of erbB2
      and Akt. In mice UM-UC-3 tumor xenografts model, Hsp90 inhibitors successfully
      potentiated anti-tumor activity of CRT. These results encourage clinical trials
      of Hsp90 inhibitors to overcome CRT resistance in patients with MIBC.

PMID- 22134245
TI  - Loss of stromal caveolin-1 expression in malignant melanoma metastases predicts
      poor survival.
AB  - Caveolins are the principal protein component of caveolae, plasma membrane
      invaginations found in most cell types. Caveolin-1 (Cav-1) plays a major role in
      oncogenesis through its various functions in lipid transport, membrane
      trafficking, and signal transduction. Increased expression of Cav-1 in tumor
      cells has been associated with aggressiveness and poor survival. More recently,
      loss of stromal Cav-1 expression was linked to poor survival and increased
      metastatic potential in breast and prostate cancer. To date, there is no study
      addressing the clinical significance of Cav-1 expression in malignant melanoma
      (MM). Our study consisted of 44 cases of MM: 12 MM lymph node metastases from
      patients with short survival, 12 MM lymph node metastases from patients with long
      survival and 20 primary MM. All cases were stained with Cav-1 antibodies. Cav-1
      expression in melanoma and stromal cells was quantified using a 3 point scale: 0
      = no staining, 1 = diffuse weak staining or strong staining in < 30% of cells,
      and 2 = diffuse strong staining. A score of 0-1 represented low Cav-1 expression
      and a score of 2 represented high Cav-1 expression. In patients with MM lymph
      node metastases, a low stromal Cav-1 expression was associated with shorter
      survival when compared to the high stromal Cav-1 expression group (median
      survival 252 days versus 3,508 days, p value 0.0054). Conversely, high Cav-1
      expression in melanoma cells was associated with a longer survival in primary MM
      (p < 0.0001). In conclusion, high expression of stromal Cav-1 correlates with
      longer survival in malignant melanoma metastases, and high expression of Cav-1 in
      melanoma cells correlates with longer survival in primary malignant melanoma.

PMID- 22134244
TI  - Unmasking a temperature-dependent effect of the P. anserina i-AAA protease on
      aging and development.
AB  - Different molecular pathways involved in maintaining mitochondrial function are
      of fundamental importance to control cellular homeostasis. Mitochondrial i-AAA
      protease is part of such a surveillance system and PaIAP is the putative ortholog
      in the fungal aging model Podospora anserina. Here we investigated the role of
      PaIAP in aging and development. Deletion of the gene encoding PaIAP resulted in a
      specific phenotype. When incubated at 27 degrees C, spore germination and
      fruiting body formation are not different from that of the corresponding wild
      type strain. Unexpectedly, the lifespan of the deletion strain is strongly
      increased. In contrast, cultivation at an elevated temperature of 37 degrees C
      leads to impairments in spore germination and fruiting body formation, and to a
      reduced lifespan. The higher PaIAP abundance in wild-type strains of the fungus
      grown at elevated temperature and the phenotype of the deletion strain unmasks a
      temperature-related role of the protein. The protease appears to be part of a
      molecular system that has evolved to allow survival under changing temperatures
      as they characteristically occur in nature.

PMID- 22134246
TI  - Thiostrepton, proteasome inhibitors and FOXM1.

PMID- 22134247
TI  - Validation of affinity reagents using antigen microarrays.
AB  - There is a need for standardised validation of affinity reagents to determine
      their binding selectivity and specificity. This is of particular importance for
      systematic efforts that aim to cover the human proteome with different types of
      binding reagents. One such international program is the SH2-consortium, which was
      formed to generate a complete set of renewable affinity reagents to the SH2
      domain containing human proteins. Here, we describe a microarray strategy to
      validate various affinity reagents, such as recombinant single-chain antibodies,
      mouse monoclonal antibodies and antigen-purified polyclonal antibodies using a
      highly multiplexed approach. An SH2-specific antigen microarray was designed and
      generated, containing more than 6000 spots displayed by 14 identical subarrays
      each with 406 antigens, where 105 of them represented SH2-domain containing
      proteins. Approximately 400 different affinity reagents of various types were
      analysed on these antigen microarrays carrying antigens of different types. The
      microarrays revealed not only very detailed specificity profiles for all the
      binders, but also showed that overlapping target sequences of spotted antigens
      were detected by off-target interactions. The presented study illustrates the
      feasibility of using antigen microarrays for integrative, high-throughput
      validation of various types of binders and antigens.

PMID- 22134248
TI  - Spinal Cord is almost 50 years young.

PMID- 22134249
TI  - Medicine cannot thrive on enforced mediocrity that will eventually defeat us all.

PMID- 22134250
TI  - Principles of plastic surgery portrayed by the professional life of Dr John Peter
      Mettauer.
AB  - Regarded as "America's first plastic surgeon," Dr John Peter Mettauer's
      professional life displays 3 fundamental keystones of plastic surgery: education,
      innovation, and practice. To fully appreciate the history of our plastic surgery,
      one must look beyond a purely factual recount of noteworthy actions performed
      decades ago. Fundamental principles that governed achievements of our
      predecessors remain applicable even today. Dr Mettauer thrived as a medical
      student under the influence of distinguished professors in medicine at the
      University of Pennsylvania. Later, he continued to propagate their basic tenets
      when he established his medical institute in 1837. Throughout his life, Dr
      Mettauer combined ingenuity with scientific inquiry to devise numerous
      unprecedented surgical techniques and instruments. He was a prolific writer and
      exquisitely documented his work in medical journals for the benefit of both
      contemporary and future surgeons. One of Dr Mettauer's momentous achievements in
      plastic surgery that displays his remarkable capabilities was his contributions
      to management of both simple and complicated cases of cleft palate. He was the
      first to describe relaxing lateral incisions for treating complete cleft palates
      and, incidentally, was the first to successfully treat this in America. He
      invariably replicated similar success in establishing techniques for treating a
      wide range of anatomic deformities. Cumulatively, Dr Mettauer's lifelong
      commitment and diligence have truly laid a foundation for the eventual progress
      and success in the field of plastic surgery.

PMID- 22134251
TI  - Asymmetric, disproportionate craniofacial hyperostoses of mosaic pattern in a
      patient not meeting Proteus syndrome criteria.
AB  - A 34-year-old patient with asymmetric hyperostosis of the craniofacial skeleton
      much more pronounced on the right side is presented. A long-term follow-up of 16
      years showed progression of overgrowth even after skeletal maturity and despite
      repeated surgical corrections focusing on regional reduction of the hyperostoses.
      Clinical situation during infancy, adolescence, and adulthood is documented.
      Although the craniofacial hyperostosis in the patient was indicative of the
      Proteus syndrome, the applicable criteria were not met. Proportionate mild
      hemihypertrophia/hyperplasia of the patient's right extremities also exclude an
      oligosymptomatic variant of the Proteus syndrome limited to the skull. Both
      surgical strategies and difficulty of a diagnostic classification are discussed.

PMID- 22134252
TI  - Prospective clinical assessment of morbidity after chin bone harvest.
AB  - The aim of this prospective research was to assess soft tissue morbidity in the
      symphyseal region after bone graft harvesting. Thirty patients, with average age
      45 years, underwent symphyseal bone graft harvesting followed up for a period of
      12 months. Follow-up involved neurosensory testing of 2-point discrimination,
      static light touch, brush directional stroke, pinprick, and thermal
      discrimination to cold and hot; the statistical analysis was performed using
      McNemar test and Friedman test with P < 0.05. The results showed that 50% of
      patients had postoperative morbidity in the first month after surgery showing
      statistical positive relation with surgery (P < 0.05); at 6 months, this
      situation diminished to 23%, and at the end of the monitoring period (1 year);
      the neurosensory tests revealed no persistent morbidity. In conclusion, all
      neurosensory tests revealed high morbidity in the first month with total
      resolutions at 1-year follow-up; however, this complication associated to surgery
      is indispensable to discharge the patient properly.

PMID- 22134253
TI  - Composite fronto-orbital reconstruction using a subscapular chimeric flap.
AB  - Composite defects of the fronto-orbital region represent a reconstructive
      challenge. Total autogenous reconstruction requires a thin pliable skin flap
      along with a bony component that can be osteotomized predictably. The
      thoracodorsal artery perforator/scapular bone chimeric flap provides a reliable
      single-stage method to cover difficult composite forehead defects where local
      options are unsuitable or have been exhausted. We present a patient with a
      traumatic fronto-orbital defect that has been successfully reconstructed using
      this flap. The report of this case illustrates well the versatility of the
      subscapular system as a donor site for difficult composite posttraumatic defects
      where tissue components need to be inset in a complex three-dimensional fashion.

PMID- 22134254
TI  - Histopathologic evaluation of autologous blood injection to the temporomandibular
      joint.
AB  - PURPOSE: Chronic recurrent temporomandibular joint dislocation is treated by
      surgical and nonsurgical techniques described in the literature. However, these
      techniques have some complications noted in the literature. Recently, the
      autologous blood injection in temporomandibular joint technique has been applied
      to treat chronic temporomandibular joint dislocation. However, to date, there has
      been no study that describes the histopathologic effects of autologous blood
      injection within the literature. The aim of this study was to evaluate the
      histopathologic effects of autologous blood injection in rabbit temporomandibular
      joints. METHODS: Eight New Zealand white rabbits underwent bilateral autologous
      blood injection. After the injection, mandibles were fixed by orthodontic
      brackets and elastics for 24 hours. One rabbit was included in the control group.
      After 1-month follow-up period, the animals were killed. Temporomandibular joints
      were dissected and sent to histological examination. RESULTS: Only fibrin
      accumulations were seen in the tissue samples. There was no evidence of
      degeneration in the joint cartilage, and a fibrous bed was not formed in the
      injected regions. CONCLUSIONS: Although the procedure has successful results in
      the literature, a fibrous bed that is supposed to be the outcome of the treatment
      was not seen in the tissue samples. According to this study, therefore, the
      autologous blood injection does not change the structure of temporomandibular
      joint in rabbits.

PMID- 22134255
TI  - Three-dimensional analysis and treatment planning of hemimandibular hyperplasia.
AB  - INTRODUCTION: The advent of computed tomography (CT) provided a useful instrument
      for diagnosis and surgical treatment of patients with craniofacial malformations.
      The development of software for three-dimensional graphic simulation applied to
      CT scan has made possible the three-dimensional computerized analysis, surgical
      planning, and simulation. This kind of analysis is particularly useful in case of
      complex facial malformations, making reliable a surgical treatment in 1 step. The
      purpose of this report was to present the diagnosis and treatment planning on a
      patient with hemimandibular hyperplasia by three-dimensional cephalometric
      analysis. METHODS: A 20-year-old young woman who presented with hemimandibular
      hyperplasia was investigated with CT scan and plaster cast mounted on an
      articulator; a two-dimensional manual and computerized cephalometric analysis was
      also developed on frontal and lateral cephalograms. Images in DICOM format were
      processed on a PC by means of commercial software, thus obtaining the three
      dimensional reconstruction of the skeletal structures. RESULTS: Three-dimensional
      CT permits to program skeletal corrections and to foresee surgical outcomes with
      adequate realism. Surgical planning based on three-dimensional CT makes it easy
      and reliable to achieve the correction of the malformation in a single surgical
      intervention. CONCLUSIONS: The virtual three-dimensional CT model, a versatile
      diagnostic aid, has proven to be effective in the exact reproduction of bone and
      soft tissue anatomy, thus helping in the diagnosis, surgical planning, and
      simulations. Three-dimensional analysis is particularly indicated in case of
      complex asymmetric malformations, in which the more accurate reproduction of the
      individual anatomy can be very useful in implementing surgical results.

PMID- 22134256
TI  - Successful treatment of nonunion after sliding genioplasty.
AB  - Because chin is a major component of the lower face, underprojection,
      overprojection, and asymmetry of chin have been addressed via various surgical
      approaches. Sliding genioplasty is a popular technique to resolve this problem.
      This technique is rarely known to have postoperative complications, including
      nonunions. We experienced 1 case of nonunion after sliding genioplasty and
      treated it successfully.A 25-year-old woman who underwent sliding genioplasty 10
      years ago at a local clinic visited our institute owing to displeasing appearance
      of the chin. Ten months ago, nonunion was diagnosed, and the patient underwent a
      second operation. We performed a longer incision than the previous operation and
      removed screws, plate, and an alloplastic material that was inserted previously.
      Shaving of the nonunion margins, refixation, and recontouring were performed, and
      bone chips acquired from the recontouring procedure were inserted into the
      interim space. During follow-up, no complications were observed, and bone union
      was completed on radiologic examination. Appropriate fixation is very important
      to prevent nonunion after sliding genioplasty. For appropriate fixation, getting
      a sufficient surgical field is indispensable, and shaving the nonunion margins,
      refixation, and bone chip implantation are helpful to address this complication.

PMID- 22134257
TI  - Ankyloglossia correction: Z-plasty combined with genioglossus myotomy.
AB  - Ankyloglossia or tongue-tie is a disease in which the tongue has a mobility
      disorder because the lingual frenulum is short and tight, and as a result, the
      tongue tip is tied up. It may be asymptomatic or may cause various problems such
      as articulation disorder. Surgical treatment is required in many of the patients,
      and conventional methods release only the mucosal layer of the frenulum. However,
      conventional method alone is not as effective; therefore, the authors studied the
      addition of a partial myotomy of the genioglossus muscle along with mucosal layer
      release for treatment. The authors performed the surgery on 106 patients from
      2005 to 2010, and during the surgery, the mucosal layer was released through Z
      plasty after myotomy was performed on the contracted genioglossus muscle. During
      the follow-up, none of the patients showed signs and symptoms of tongue mobility
      impairment or articulation disorder caused by the partial myotomy of the
      genioglossus muscle, and a satisfactory outcome was obtained in achieving
      mobility of the tongue tip. Because tongue mobility disorder in ankyloglossia is
      accompanied by the contracture and shortening of the genioglossus muscle, an
      improved outcome is expected in the projection and mobility of the tongue tip
      from the combined application of conventional Z-plasty and genioglossus muscle
      release.

PMID- 22134258
TI  - Periosteal reflection on the medial approach to the mandibular ramus in sagittal
      split ramus osteotomy.
AB  - We describe the modified medial opening to avoid blind procedures and to ensure
      periosteal dissection. The mucosal incision started behind the second molar and
      then wings laterally and forward at the lateral aspect. The medial subperiosteal
      dissection begins at the lingual border of the retromolar triangle. Minimal
      medial subperiosteal tunneling is performed only to identify the lingula. A
      medial osteotomy is performed above and 5 to 6 mm posterior to the lingula.

PMID- 22134259
TI  - Acute cranial decompression in Meckel-Gruber syndrome and slit-ventricle syndrome
      with craniocephalic disproportion.
AB  - Slit-ventricle syndrome (SVS) is characterized by headaches associated with
      subnormal ventricular size in patients with shunt-treated hydrocephalus. It
      commonly occurs in children who have had shunts placed at an early age and is
      diagnosed when computed tomography scans are carried out to investigate suspected
      shunt obstruction with an accompanying rise in intracranial pressure (ICP).
      Overdrainage of cerebrospinal fluid may additionally result in craniocephalic
      disproportion, potentially by dampening the normal expansile pulsations of the
      dura against the skull, which leads to craniostenosis. Management is
      controversial because many strategies have only short-term benefit, and surgical
      intervention is understandably often seen as a last resort.We present a case of a
      child with SVS and craniocephalic disproportion who was treated with urgent
      cranial expansion due to rising ICP. Intraoperative ICP monitoring demonstrates a
      rapid and sustained drop in ICP, and the patient made an uneventful return to his
      premorbid condition. We conclude that cranial vault expansion should be
      considered as an effective treatment for postshunt craniocephalic disproportion
      in patients with SVS.

PMID- 22134260
TI  - A simple "fishtail flap" for surgical correction of microstomia.
AB  - Treatment of microstomia, whether congenital or acquired, has long challenged the
      ingenuity of surgeons. In all instances, the challenge remains the ability to
      preserve function and provide and maintain reasonable aesthetics. The following
      case report presents 2 different cases of surgical correction of microstomia,
      resulting from flap reconstructions after perioral tumor surgery. We developed a
      technique that uses pericommissural mucomuscular advancement flap, "a simple
      fishtail flap," and used this to correct deformed oral commissures in an attempt
      to elongate the oral aperture in a functional and aesthetically acceptable manner
      without recurrence. Results have shown that, with the use of our fishtail design,
      we can restore the unique architecture of the oral commissure with the
      postoperative intercommissural distance improved by more than 10 mm and the
      interincisal width enlarged by approximately 5 mm. Our solution was functional
      and aesthetically acceptable, as well as simpler and cheaper, in comparison with
      the traditional surgical methods that are usually expensive, complex, and less
      practical. We believe that, in cases in which either the contracture is mild or a
      commissurotomy can be expected to increase the width and the general size of the
      oral aperture, this relatively conservative technique, if judiciously used, can
      be performed with ease and safety with good results.

PMID- 22134261
TI  - A quick guide to positioning the transbuccal set.
AB  - Exact positioning of the transbuccal set can be tricky, especially under
      aggravating circumstances as present scarring or high body mass index. It may
      result in multiple skin incisions. This article presents a simple and fast
      guidance technique that can help in the exact positioning of skin incision and
      transbuccal set.

PMID- 22134262
TI  - Microsurgical treatment of frontal mucocele sequelae.
AB  - Skull base surgery has undergone a revolution in recent decades with the
      introduction and development of new surgical approaches correlated with many
      modifications in this anatomically and functionally complex area. The most
      important progress has been possible with the advent of microsurgical flaps,
      which allow for the movement of large masses and different tissue components,
      providing effective separation and coverage of the endocranial content,
      replacement of the composite craniofacial defects, and reconstruction of poorly
      vascularized areas. To reduce the incidence of complications in the treatment of
      frontal recurrent mucoceles, accurate planning of reconstruction is mandatory. We
      introduce 2 cases involving anterior cranial base repair after radical resection
      of chronically infected tissues in patients affected by frontal recurrent
      mucoceles. Reconstruction was accomplished through a forearm flap and a frontal
      bone reconstruction with custom-made prosthesis.

PMID- 22134263
TI  - Subankylotic ostectomy for release of TMJ ankylosis using the transmasseteric
      anterior parotid approach.
AB  - Twelve patients with temporomandibular joint ankylosis (5 bilateral and 7
      unilateral) with preoperative maximal mouth opening ranging from 0 to 11 mm
      (mean, 2.25 [SD, 3.19] mm) were treated with a subankylotic ostectomy. Inclusion
      criteria in the study were patients older than 18 years with restricted mouth
      opening of less than 30 mm and radiographic evidence of temporomandibular joint
      ankylosis. The mean maximal postoperative mouth opening was 38.92 (SD, 3.11) mm.
      All patients showed good functional rehabilitation in terms of movement and
      speech with no radiographic evidence of recurrence and no occurrences of
      temporary or permanent facial nerve palsy, sialoceles, or salivary fistulae. As
      this technique does not encroach upon the mass of ankylotic bone but creates a
      pseudarthrosis beneath it, chances of recurrences are minimized. The entire
      length and width of the right ramus from the condyle to the angle region can be
      accessed with this technique.

PMID- 22134264
TI  - Facial mobility after bimaxillary surgery in class III patients: a three
      dimensional study.
AB  - Quantifying soft tissue changes after orthognathic surgery is increasingly
      important in surgical planning, but little is actually known about the changes in
      facial mobility after surgery. In the current study, we investigated facial
      mimics in patients before and after orthognathic surgery. Eleven patients with
      jaw discrepancy requiring maxillary and/or mandibular surgery were considered.
      Facial landmarks were applied, and facial surface data were acquired using a
      three-dimensional laser scanner before surgery and after 3, 6, and 12 months. The
      facial movements were frowning, eye closure, grimace, smiling, and lip purse.
      They were described in terms of surface and landmark displacements. Mean and SD
      were calculated for the right and left sides of the face and compared with normal
      values previously obtained in control subjects. We compared the results in 4
      groups of patients: all the patients together (group A), bimaxillary surgery
      (group B), basal surgery without ancillary procedures (group C), and basal
      surgery plus rhinoplasty and/or genioplasty (group D). After surgery,
      modifications of symmetry were evident in many subjects, but after 1 year, facial
      movements were statistically similar to presurgical registrations. In smiling,
      the single case observations revealed a postsurgical improvement of amplitude in
      8 subjects. In conclusion, orthognathic surgery did not significantly modify
      facial mobility in the long term. On the contrary, the amplitude of movement
      during smiling seems to increase in the majority of subjects. Our evaluation of
      three-dimensional laser scanning of facial movement showed that it can detect
      small posttreatment changes on soft tissues.

PMID- 22134265
TI  - Neuroanatomy of extensor digitorum brevis muscle for reanimation of facial
      paralysis.
AB  - PURPOSE: This study explores the vascular and morphologic anatomy of extensor
      digitorum brevis (EDB), which can be alternatives to donor muscles used in
      functional muscle transfer in long-standing facial paralysis reanimation.
      METHODS: A total of 14 EDB muscles from 7 embalmed cadavers were dissected and
      examined. Diameters and lengths of major and minor arteries supplying the muscle,
      venous pedicle diameter, neural pedicle diameter and length, their entrances into
      the muscle, the extendibility of neurovascular pedicles, when necessary, and the
      morphology of muscles were evaluated. RESULTS: Mean results obtained for EDB
      muscle in the study were as follows: the longest distance between the starting
      point and the area where the tendon started was a mean of 5.1 +/- 0.1 cm (range,
      4.8-5.4 cm), the distance between the widest points was 4.2 +/- 0.3 cm (range,
      3.7-4.9 cm), the thickest area was 1.4 +/- 0.8 cm (range, 1-1.9 cm), and surface
      area was a mean of 32.1 +/- 1.2 cm (range, 29.8-35.7 cm). The mean length of the
      major artery is type 2 according to Mahtnes-Nahai classification and was found to
      be 2.1 +/- 0.03 cm (range, 1.6-3.2 cm), and its diameter was found to be 1.95 +/-
      0.15 mm (range, 1.7-2.1 mm). Mean length and diameter of the nerve providing
      motor innervation to the muscle were found to be 2.3 +/- 0.03 cm (range, 2.1-2.6
      cm) and 2.4 +/- 0.08 mm (range, 2-2.9 mm), respectively. CONCLUSION: As a result
      of this preliminary study, we think that the morphologic and neurovascular
      structures of this muscle are suitable for use in long-standing facial paralysis
      reanimation.

PMID- 22134266
TI  - Digital radiographic evaluation of the level of alveolar bone crest in external
      hexagon implants submitted to 2 types of implant abutments under immediate
      loading.
AB  - PURPOSE: The aim of this study was to evaluate by means of digital radiography
      the behavior of the alveolar bone crest in external hexagon implants following
      the use of 2 different types of abutments, one for conventional cemented
      prosthesis and one for modified cemented prosthesis. METHODS: Ten external
      hexagon implants (platform 4.1) were placed in 5 patients. Initial
      instrumentation was carried out to obtain primary stability of the temporary
      prostheses under immediate loading. Each patient received both abutments for
      conventional and modified cemented prosthesis. Standardized digital periapical
      radiographies were performed at times T0 (immediately after implant placement)
      and T1 (4 months after implant placement). A straight line was initially
      established from the implant platform to the distal and mesial peri-implantar
      marginal bone tissue (immediately in contact with the implant) and measured by
      digital radiography, using Sidexis version 2.3 (Sirona Dental Systems GmbH,
      Bensheim, Germany) software. The data were submitted to paired-samples t-test
      analysis. RESULTS: There was no significant difference between the conventional
      and modified cemented prosthesis. In both cases, t-test results were within the
      null hypothesis level. CONCLUSION: The abutment for the modified cemented
      prosthesis resulted in no significant radiographic difference of alveolar bone
      crest height, when compared with the conventional cemented prostheses.

PMID- 22134267
TI  - Multidisciplinary surgical management of cherubism complicated by
      neurofibromatosis type 1.
AB  - Cherubism is a rare, autosomal dominant, mostly self-limiting disease of the jaw.
      It is characterized by bilateral fibrous tissue hyperplasia, giant cell
      proliferation, and bony degeneration in the lower facial skeleton, which can
      result in a massive and severely deforming prominence of the maxillomandibular
      structure. This case study examines the multidisciplinary management of a severe
      case of cherubism complicated by neurofibromatosis type 1, 2 codominant
      nonsegregating conditions that were clinically and genetically diagnosed, an
      extremely rare combination. Adequate mandibular reduction, reconstruction, and
      dental implantation afforded good restoration of oral function as well as a
      marked aesthetic improvement. METHODS: A 14-year-old Fijian girl was referred to
      our unit for management of severe overgrowth of her mandible that compromised her
      speech and deglutition. In addition, she displayed clinical features consistent
      with neurofibromatosis type 1. Radiologic, histologic, and genetic analyses
      confirmed the diagnosis of both conditions. Our craniofacial multidisciplinary
      team undertook mandibular reconstruction followed by placement of osseointegrated
      dental implants. RESULTS: Mandibular reduction, reconstruction, and dental
      implantation resulted in a significantly improved functional and aesthetic
      outcome with no further regrowth at 3-year follow-up when she returned to the
      United Kingdom for osseointegrated dental implant insertion. CONCLUSIONS: The
      successful outcome of this surgically challenging, grossly disfiguring, and rare
      condition was largely a result of the combined input from our multidisciplinary
      team, adequate preoperative planning, and the use of a novel surgical technique
      in debulking and reconstructing her mandible.

PMID- 22134268
TI  - Supporting strength of septal extension grafts.
AB  - The aim of this study was to measure the supporting strength of septal extension
      grafts according to the linking methods. Swine scapular cartilages were
      harvested, and these were cut into pieces measuring 10 * 20 * 2 mm. For the
      overlapping type, a 4-mm length of each cartilage was overlapped and fixed using
      2 interrupted sutures. For the interdigitating type, 2 parallel incisions (5 mm
      in length) were made 3 mm apart on each cartilage. The tongue of 1 cartilage was
      slipped into the groove of the other cartilage, and 2 fixation sutures were made.
      One end of the connected cartilage was gripped with a vise, and a 3-0 silk was
      passed through the other tip. The degree of sagging of the connected cartilage
      was measured using micrometers according to the power of a force gauge. The
      contralateral bending force, the ipsilateral bending force, and the shearing
      force were measured. In each group, 8 assembled extension grafts were measured
      and then analyzed with independent sample t-tests.For the contralateral bending
      force, there was no significant difference between the overlapping type and the
      interdigitating type (P = 0.494 for 5-mm bending and 0.834 for 10-mm bending).
      For the ipsilateral bending force, there was also no significant difference
      between the overlapping type and the interdigitating type (P = 0.247 for 5-mm
      bending and 0.529 for 10-mm bending). For the shearing force, there was no
      significant difference between the overlapping type and the interdigitating type
      (P = 0.495 for 5-mm bending and 0.462 for 10-mm bending). When performing a
      septal extension graft, the overlapping type is thought to be technically easier
      than the interdigitating type. Because the bending force and the shearing force
      are similar for the 2 methods, the easier overlapping type extension graft might
      be preferred when performing nasal tip surgery.

PMID- 22134269
TI  - Prosthetic platforms in implant dentistry.
AB  - The use of implant-supported prosthesis to replace missing teeth became a
      predictable treatment. Although high success rate has been reported, implant
      treatment is suitable to complications, failures, and limitations such as peri
      implant bone loss after implant loading. Stress evaluation on the bone-abutment
      implant interface has been carried out to develop new designs of prosthetic
      platform and to understand the stress distribution in this interface. Several
      types of prosthetic platforms are available such as external and internal
      hexagon, Morse cone connection, and the concept of platform switching. Therefore,
      this study aimed to critically describe the different options of prosthetic
      platforms in implant dentistry, by discussing their biomechanical concepts,
      clinical use, and advantages and disadvantages. It was observed that all types of
      prosthetic platforms provided high success rate of the implant treatment by
      following a strict criteria of indication and limitation. In conclusion, a
      reverse planning of implant treatment is strongly indicated to reduce implant
      overload, and the use of advanced surgical-prosthetic techniques is required to
      obtain a long-term success of oral rehabilitations.

PMID- 22134270
TI  - Photoelastic analysis of the distribution of stress in different systems of
      overdentures on osseous-integrated implants.
AB  - OBJECTIVE: The aim of this study was to evaluate the distribution of generated
      stress around implants and adjacent bone tissue using different implant-retained
      overdenture designs through photoelastic analysis. METHODS: Over an edentulous
      human mandible, achieved from a human model, 2 or 4 microunit analog abutments
      were embedded (Master; Conexao Systems Prosthodontics, Sao Paulo, Brazil),
      settled in the interforaminal region. Three models of photoelastic resin (Araltec
      Chemicals Ltda, Hunstman, Guarulhos, Sao Paulo, Brazil), with 2 or 4 incorporated
      implants and microunit abutments, were obtained from molds using silicone for
      duplication. Inclusion, finishing, and polishing procedures were applied on the
      frameworks. This study was based on 3 different mechanisms of implant-retained
      mandibular overdentures: O'ring (GI), bar-clip (GII) (both with 2 implants), and
      their association (GIII) (with 4 implants). After the adaptation of each
      overdenture system on the photoelastic models, 100-N alternate occlusal loads
      were applied on back-side and front-side regions. The photoelastic analysis was
      made with the aid of a plain polariscope linked to a digital camera, Sony
      Cybershot alpha100, which allowed visualization of the fringes and registration
      of images on digital photographs. RESULTS: The results demonstrated higher
      tension concentrated over the GIII, with a flat distribution of stress to the
      posterior ridge and overload on the posterior implants. GI showed the smaller
      stress level, and GII, intermediate level; there was distribution of stress to
      the posterior ridge in these 2 groups. CONCLUSION: The use of bar attachment
      proved to be a better alternative, because it showed a moderate level of tension
      with a more uniform stress distribution and possessed higher retention than did
      the ball system.

PMID- 22134271
TI  - Maxillary bone defect reconstruction using porous polyethylene implants.
AB  - PURPOSE: The aim of this study was to evaluate the bone repair process in the
      maxillary sinus in monkeys treated with high-density porous polyethylene (Medpor)
      METHODS: Four capuchin monkeys (Cebus apella) were submitted to bilateral
      horizontal osteotomies in the anterior wall of the maxillary sinus and divided
      into 2 groups: control group, left side with no implants, and porous polyethylene
      group, right side with Medpor. After a period of 145 days after implant
      placement, the maxillae were removed for histologic and histometric analyses.
      RESULTS: Bone repair in osteotomized areas took place by connective tissue in
      58.5% and 58.7% in the control group and the porous polyethylene group,
      respectively. In the contact surface with Medpor, bone repair occurred in 41.3%.
      CONCLUSIONS: Medpor was not reabsorbed within the period of this study and
      allowed bone repair surrounding it. The porous polyethylene constitutes a
      feasible alternative for bone defect reconstruction.

PMID- 22134272
TI  - Critical-size defect ossification:  effect of leporid age in a cranioplasty
      model.
AB  - The ability of the human cranium to ossify full-thickness defects depends on the
      size of the area and the age of the patient. An adult leporid cranioplasty model
      is commonly used to study inlay cranioplasty materials; the influence of age on
      ossification is unknown in this model. The purpose of this study was to determine
      the effect of age on healing of a rabbit critical-size defect. Nineteen rabbits
      were divided into 4 groups: group 1 (n = 5) aged 4 months, group 2 (n = 4) aged 8
      months, group 3 (n = 5) aged 12 months, and group 4 (n = 5) aged 16 months. A 17
      * 17-mm defect was created in the parietal bones with preservation of the
      underlying dura. Animals underwent micro-computed tomography 4 months
      postoperatively to determine ossification of the defect. Group 1 defects healed
      by 28.5% (SD, 12.5%), group 2 defects ossified by 37.2% (SD, 5.7%), group 3
      defects closed by 28.2% (SD, 11.9%), and group 4 defects healed by 39.4% (SD,
      11.0%). No difference in ossification was found between groups (P =
      0.31).Leporids as young as 4 months do not close a 17 * 17-mm defect;
      ossification is similar to animals as old as 16 months. Rabbits 4 months or older
      are suitable for a calvarial critical-size defect model.

PMID- 22134273
TI  - Surgical management of impacted teeth using three-dimensional computed
      tomography.
AB  - The surgical removal of impacted, supernumerary, or ectopic teeth is a routine
      procedure to the dental surgeon. Because any and all surgical interventions
      involve anatomic considerations that predispose the patient to a high risk of
      incidents or complications, it is absolutely necessary to precisely determine the
      location of the enclosed teeth, to better plan the procedure. Even though the
      conventional radiographic techniques are commonly used to detect the presence of
      such teeth, they can present deficiencies. In those situations, additional
      examinations can be requested. In this article, we are reporting the case of a 12
      year-old patient, whose third superior molars appeared in a very atypical
      position. We chose to request a computed tomography and three-dimensional
      manipulation of the obtained images. This article, as its main goal, highlighted
      the importance of computed tomography and of three-dimensional reconstructions as
      a tool to precisely determine the location of enclosed teeth, thus allowing for a
      better planning of the surgery and a safer surgical intervention.

PMID- 22134274
TI  - Simultaneous palatal pleomorphic adenoma and mandibular keratocystic odontogenic
      tumor in a pediatric patient.
AB  - BACKGROUND: Neoplasms of the salivary gland account for 3% of all head and neck
      tumors; most of these occur in the parotid gland and are benign; 80% of them are
      pleomorphic adenomas. Benign neoplasms of the salivary gland are rare in children
      compared with adults. Keratocystic odontogenic tumor (KCOT) is considered the
      second most frequent neoplasm of all odontogenic tumors after the ameloblastoma.
      In the present report, we introduce the unusual presentation of a child with a
      simultaneous pleomorphic adenoma of the right hard palate and a KCOT of the left
      mandibular angle. DISCUSSION: The case is significant for 2 reasons; according to
      the literature, there are few reports of pleomorphic adenoma arising from a minor
      salivary gland of the palate in a patient younger than 18 years. This is to our
      knowledge the first recorded instance of simultaneous palatal pleomorphic adenoma
      and mandibular KCOT occurring in a child.

PMID- 22134275
TI  - Giant desmoplastic fibroma in the anterior zone of the maxilla.
AB  - Desmoplastic fibroma (DF) is a rare intraosseous benign neoplasm that represents
      less than 1% of the osseous tumors. This lesion can be locally aggressive, and
      the rate of recurrence is frequently high.A 34-year-old male patient was referred
      to our clinic presenting a tumor in the anterior zone of the maxilla. The oral
      examination revealed a hard and lobulated tumor, affecting teeth 13 to 26. The
      radiographic examination, orthopantomography, and computed tomography revealed a
      radiolucent, multilocular, well-defined image, which extended from tooth 13 to
      the mesial root of tooth 26, provoking marked expansion, thinning, and
      perforation of the buccal and palatal cortical plates. A provisional diagnosis of
      aggressive odontogenic tumor was made, and block resection of the tumor was
      carried out. Intraoperatively, the tumor was lobulated, composed of a homogenous
      fibrous tissue, hard, and white-yellowish. The histologic analysis leads to a
      diagnosis of DF.Desmoplastic fibroma of the oral cavity is a rare benign
      intraosseous tumor, especially when it involves the upper maxilla and the
      anterior region. The main clinical and pathologic differential diagnosis in our
      case was central odontogenic fibroma. The most suitable treatment option for DF
      of the oral cavity is a controversial issue, but block resection is the therapy
      reporting a lower recurrence. Finally, an interesting feature of this
      intraosseous neoplasm, if located in the oral cavity, refers to the different
      clinical pattern that might present depending on location.

PMID- 22134276
TI  - Ameloblastic carcinoma:  rare localization of a rare neoplasm.
AB  - Ameloblastic carcinoma (AC) is a rare neoplasm of the maxillofacial district. It
      usually occurs in the posterior region of the jaw. In one third of cases, it
      occurs in the maxilla, usually in the posterior portion. From a review of
      international literature, we found 60 cases described. A 77-year-old patient
      presented to our division of maxillofacial surgery after the onset of a vegetans
      lesion of the maxilla. He had already been subjected to a first histologic
      examination that detected an AC. Surgery consisted of removal of a trapezoidal
      flap of the maxillary bone containing the mass. Histologic examination confirmed
      preoperative biopsy findings. Because of the low compliance, we did not plan for
      surgical reconstruction.Surgical resection is the treatment of choice for this
      kind of lesion, leaving at least a 2-cm free margin. Neoadjuvant radiotherapy may
      be useful for tumor debulking.

PMID- 22134277
TI  - Recurrent oral pyogenic granuloma in port-wine stain.
AB  - Pyogenic granuloma (PG) is a benign inflammatory lesion, nonneoplastic in nature,
      which occurs in the oral cavity and skin. This lesion arises in response to
      various stimuli such as low-grade local irritations, traumatic injury, or
      hormonal factors. Recently, in some cases, the occurrence of recurrent PGs in
      skin associated with vascular lesions, such as port-wine stains, has been
      described. It has been postulated that this association is promoted by
      arteriovenous anastomoses in the vascular lesions, leading to the development of
      PG. The authors discuss 2 cases of recurrent PG in patients with a port-wine
      stain, and the treatment options adopted.

PMID- 22134278
TI  - The importance of remaining teeth reconstruction in the definite obturator for a
      hemimaxillectomy patient.
AB  - OBJECTIVE: The aim of this clinical report was to present and discuss the
      clinical procedure and the treatment considerations of prosthetic rehabilitation
      for hemimaxillectomy patients. DESIGN: A 61-year-old man was successfully treated
      with all the remaining teeth reconstruction including replacing the implant
      supported anterior fixed prosthesis and maxillary obturator. CONCLUSIONS: An
      appropriate obturator design, remaining teeth reconstruction, and establishment
      of a proper vertical dimension of occlusion are important for acceptable facial
      appearance and patient satisfaction.

PMID- 22134279
TI  - Cricoid-based extramedullary plasmocytoma.
AB  - Extramedullary plasmocytomas are solitary, vascular, soft tissue plasma cell
      tumors without evidence of multiple myeloma (MM) that represent approximately 1%
      of head and neck malignancies. Approximately one third of them disseminate to MM
      within 2 years from presentation. Extramedullary plasmocytomas have been reported
      to involve larynx in 6% to 18% of cases, most commonly affecting the epiglottis
      and the ventricle, followed in order by the true vocal cord, false vocal cord,
      aryepiglottic fold, arytenoids, and subglottis. In this report, we describe a
      case of plasmocytoma involving the cricoid, the left cricoaritenoid joint, and
      the homolateral vocal process that developed MM 1 year after primary treatment.

PMID- 22134280
TI  - Brain abscess of odontogenic origin.
AB  - Brain abscess is a rare and threatening infection, which is in a suppuration
      area, caused either by trauma, neurosurgical complication, or by a secondary
      infection of dental origin complication. The infectious process spread from the
      start focus can occur in 2 ways: hematogenous or by contiguity. The treatment
      should ideally be based on the etiological factor excision, combined with
      drainage and antibiotics as adjuvant; this philosophy is not observed in the
      reports described in the 1960s, 1970s, and 1980s. This study's goal was to report
      a case of brain abscess consequent of an odontogenic outbreak, where an adequate
      treatment was set up, but it was already in advanced stages and had as a result
      the lethal outcome. Complications from the odontogenic infections have a low
      incidence, but should never be disregarded, because they can lead to death, as
      described in this manuscript.

PMID- 22134281
TI  - Metastatic prostate adenocarcinoma associated with numb chin syndrome.
AB  - Metastatic tumors to the oral cavity are rare and account for approximately 1% of
      all malignant oral neoplasms. About 765 cases have been published in the English-
      and Chinese-language literature since 1950, with less than 6% of these cases
      corresponding to prostate cancer metastasis. Because of their uncommon incidence,
      the diagnosis of oral metastases, especially those originating from the prostate
      gland, may represent a challenge for general dentists, oral pathologists, and
      oral radiologists. Thus, the aim of this study was to describe an interesting
      case of prostate adenocarcinoma metastasizing to the posterior mandible. In
      addition, association with numb chin syndrome present in this case was discussed.

PMID- 22134282
TI  - Heterotrophic ossification on a skin graft in a postburn scar of the chin.
AB  - Some patients who have heterotrophic ossification (HO) in a postburn scar are
      occasionally seen in the clinic. The occurrence of HO following hip and abdominal
      surgery is common in males, whereas females are frequently affected following
      burns. The HO of skin grafts in burn scars of the superior body parts is
      uncommon, especially on the face. We report a recent case of a male patient in
      whom HO arose on skin grafts on his chin. The patient presented with a history of
      a painless chin mass for 48 years. Computed tomography scan suggested that the
      mass was located within subcutaneous tissue away from the lower jaw. The density
      of the mass was almost the same as the cortical bone of the lower jaw. The mass
      was completely resected under general anesthesia. It was a rectangular mass of 3*
      0.5* 0.3 cm. Histological examination gave the diagnosis of HO, which was also
      confirmed by immunohistochemical stainings for vimentin. Recurrence was not found
      in this case by clinical and radiologic follow-up at 1 year after surgery.

PMID- 22134283
TI  - A benign isolated schwannoma of the orbit.
AB  - Schwannomas are benign encapsulated tumors, originating from Schwann cells of the
      peripheral nerves. Schwannomas accounts for approximately 1% of all orbital
      tumors. Most schwannomas originate from branches of the oculomotor, trochlear,
      trigeminal, and abducens nerves and from sympathetic and parasympathetic fibers.
      The progressive growth may cause compression of the optic nerve with papilledema
      or optic atrophy. Prompt diagnosis and early treatment are necessary to avoid
      important ocular consequences. We report a successful surgical treatment of
      orbital schwannoma in a 75-year-old woman.

PMID- 22134284
TI  - Encephalomalacia in the frontal lobe:  complication of the endoscopic sinus
      surgery.
AB  - Encephalomalacia is the softening or loss of brain tissue after cerebral
      infarction, cerebral ischemia, infection, craniocerebral trauma, or other injury.
      The term is usually used during gross pathologic inspection to describe blurred
      cortical margins and decreased consistency of brain tissue after infarction.
      Multicystic encephalomalacia refers to the formation of multiple cystic cavities
      of various sizes in the cerebral cortex of neonates and infants after injury,
      most notably perinatal hypoxic-ischemic events. Chronic sinusitis has become one
      of the most common diseases in otolaryngology practice. Many of these patients
      can be managed successfully with medical therapy. Those who fail intensive
      medical therapy may be candidates for functional endoscopic sinus surgery (ESS).
      This procedure has variable complication rates and can have some serious
      consequences. Serious complications of functional ESS are very rare, but
      cerebrospinal fluid leak, meningitis, hemorrhage, infection, or vision loss has
      been reported in a few cases. In this study, we present a 57-year-old man with
      encephalomalacia after a penetrating brain injury incurred during ESS.

PMID- 22134285
TI  - Maxillonasal osteochondral complex repair in maxillonasal dysplasia.
AB  - Surgical treatment of maxillonasal dysplasia or Binder syndrome is a challenge
      for surgeons. Its aim is to replace or substitute the missing or malformed
      anatomic structures. The authors report a comprehensive analysis for the
      understanding of the mechanisms resulting in the lack of maxillonasal development
      observed in Binder syndrome. The evolution of the surgical treatment due to
      facial function analysis is explained, and the surgical treatment of 20
      consecutive cases over the last 20 years is reviewed, illustrated by three
      dimensional reconstruction to emphasize the choice made and the results obtained.
      Bone grafts were always performed, and an arrow-shaped graft for the neospine
      reconstruction is described. This analysis allowed the authors to ameliorate
      patient self-image subsequently to facial contour improvement.

PMID- 22134286
TI  - Nasofrontal heterotopic ossification following lymphangioma resection.
AB  - Heterotopic ossification (HO) is the formation of mature lamellar bone in soft
      tissues. Heterotopic ossification can occur locally following surgical trauma,
      most commonly after total hip arthroplasty. Periosteal stripping, organizing
      hematoma, and extensive soft tissue dissection have been associated with
      subsequent HO. Craniomaxillofacial HO is rare and almost always associated with
      injury to the muscles of mastication. We present a report of biopsy-established
      HO of the cranium. An 18-month-old boy presented with a soft, compressible mass
      in the forehead midline, which did not extend intracranially on computed
      tomography scan. Surgical exploration revealed a poorly marginated lymphangioma
      infiltrating the periosteum of the nasofrontal region. This was debulked to
      restore nasofrontal contour. Two months postoperatively, after minor accidental
      trauma, the patient developed a subperiosteal hematoma that was evacuated in the
      clinic. Eight months postoperatively, the patient returned with a visible
      nasofrontal prominence overlying a firm immobile mass. Computed tomography scan
      revealed a 3-cm horn-like osseous structure extending inferiorly from the frontal
      bone across the nasofrontal junction. The bony mass was resected via a coronal
      approach and confirmed as HO with hematopoietically active marrow.

PMID- 22134287
TI  - Controlled central advancement of the midface after Le Fort III osteotomy by a 3
      point skeletal anchorage.
AB  - A 3-point skeletal anchorage with taping screws for distraction osteogenesis
      after a Le Fort III osteotomy was applied for the first time in a severely
      mentally impaired patient where intraoral devices had to be avoided. All 3-force
      application points included the center of resistance, which allowed an optimal
      control on the resulting moment. A novel device for skeletal long-term retention
      into the nasal dorsum prevented a relapse, whereas adjustment of the midface
      position was observed. Fusioned three-dimensional computed tomography analysis
      revealed real movements not accessible by a conventional cephalometry.

PMID- 22134288
TI  - Massive osteolysis of the mandible.
AB  - We describe a case of massive osteolysis (MO) of the mandible and review related
      literature. Massive osteolysis in the craniofacial region is a rare condition
      characterized by progressive absorption of involved bones leading to craniofacial
      deformities. Currently, the cause and pathophysiology of MO are unclear, and its
      management or treatment continues to be based on clinical experiences. In our
      institution, we treat MO of the mandible with surgery; however, this kind of
      therapeutic management has been unsuccessful.

PMID- 22134289
TI  - Are facial injuries caused by stumbling different from other kinds of fall
      accidents?
AB  - The aim of this prospective study was to evaluate and compare the epidemiology
      and pattern of maxillofacial injuries caused by stumbling and other kinds of
      falls. We evaluated all patients with facial injuries due to stumbling or falls
      who presented to Besat Hospital in Hamedan, Iran, during the 2.5-year study
      period and analyzed the acquired data. Of 2990 patients with facial injuries who
      were referred to Besat Hospital during the study period, 733 (24.5%) were injured
      by stumbling, and 246 (8.2%) were injured by falls. The male-to-female ratios in
      the stumbling and falls groups were 2:1 and 1.86:1, respectively. Although the
      rate of soft tissue injuries was the same in both groups, the rate of bone
      fractures was higher in fall accidents (1.6:1). In stumbling accidents, the most
      common type of bone fracture was nasal fracture, followed by dentoalveolar,
      mandibular, and zygomatic fractures. In falls, nasal fractures were the most
      common type of bone fracture, followed by zygomatic, mandibular, and
      dentoalveolar fractures. All of the Le Fort I, II, and III fractures, nasal
      orbital-ethmoid, and frontal sinus injuries occurred in fall accidents. The rate
      of associated injuries in falls was higher than stumbling accidents. We concluded
      that the incidence, age distribution, rate, and pattern of bone fractures and the
      frequency and type of associated injuries in stumbling accidents were
      significantly different from that of fall accidents. For a good program planning
      to prevent and manage facial injuries, we recommend separate evaluation of
      stumbling and fall accidents.

PMID- 22134290
TI  - Bicalcium phosphate filling-up after calvarial unicortical harvesting in
      maxillofacial surgery.
AB  - The calvarium is one of the most common donor sites for bone grafting in
      maxillofacial and craniofacial surgery. The quality of the bone and the few after
      effects that arise in calvarium make it a very good choice for reconstruction,
      especially in preprosthetic surgery. Nevertheless, calvaria harvesting of the
      outer table can leave a depression on the scalp, which can be perceptible and
      palpable. This point is always difficult to assume for patients. This absence of
      outer-layer reconstruction of the skull could also lead to a modification of
      biomechanical characteristics and fragility of the skull. This is the reason why
      we decided to fill up the donor site with an osseoconductive biomaterial:
      bicalcium phosphate. To evaluate this reconstruction, we reviewed 20 patients who
      have undergone this procedure. All patients have been seen 6 months after
      surgery, 11 of them with computed tomographic scans of the donor site. An
      aesthetic evaluation of the result was made by the patient through a
      questionnaire. With computed tomographic scans, we made qualitative and
      quantitative evaluations of the donor site. For 2 patients of them, histologic
      examination was performed to evaluate newly formed bone. The results of this
      study suggest that filling in the donor site with bicalcium phosphate improves
      the tolerance of calvaria harvesting. Bone colonization of the osseoconductive
      biomaterials leads to the formation of a new outer table of the skull. Taking
      into account the quality of the calvarial bone and the restoration of the donor
      site, calvaria harvesting is, in our hands, one of the best choices in
      craniofacial and maxillofacial reconstruction.

PMID- 22134291
TI  - Parry-Romberg syndrome combined with hemifacial spasm: association or chance
      event?
AB  - Parry-Romberg syndrome or progressive facial hemiatrophy is a rare clinical
      entity of an unknown etiology. We present the case of a 57-year-old Chinese woman
      with Parry-Romberg syndrome and hemifacial spasm both on the right side. Its
      association was not reported before. In our report of Parry-Romberg syndrome with
      hemifacial spasm, we try to explore whether there were some relations between the
      2 diseases. We found an offending vessel compressing the root exit zone of the
      facial nerve and no evidence of vessel compression at ipsilateral trigeminal
      nerve motor rootlet.

PMID- 22134292
TI  - Primary pediatric osteosarcoma of the skull.
AB  - A 16-year-old adolescent boy presented with osteosarcoma of the left parieto
      occipital bone with no history of radiation, Paget disease, or retinoblastoma.
      The tumor presented as a painless lump, which he attributed to minor trauma 5
      months before presentation. Biopsy of the lesion was inconclusive. Complete
      surgical resection was attained. Pathology revealed a diagnosis of osteosarcoma,
      grade 1 to 2/3. Adjuvant chemotherapy commenced after tumor resection. Primary
      pediatric osteosarcoma of the skull is an exceedingly rare malignancy, with only
      a handful of cases ever reported. Complete surgical resection with negative
      margins is the key to optimizing disease-free survival. Adjuvant chemotherapy is
      recommended for high-grade tumors and in cases of incomplete resection.

PMID- 22134293
TI  - Facial infiltrating lipomatosis:  expression of angiogenic and vasculogenic
      factors.
AB  - Facial infiltrating lipomatosis causes diffuse overgrowth of subcutaneous fat,
      muscle, and bone. Because adipose tissue mass is angiogenesis dependent, the
      purpose of this study was to determine whether neovascularization is upregulated
      in this disease.Infiltrating lipomatosis tissue was collected prospectively from
      the preauricular cheek of 5 patients; neovascularization was compared to normal
      postauricular adipose. Specimens were analyzed using immunofluorescence for CD31
      (microvascular density), alpha-smooth muscle actin (pericyte marker), CD31/Ki67
      (proliferating endothelial cells), and CD34/CD133 (endothelial progenitor cells).
      Quantitative reverse transcription-polymerase chain reaction was used to
      determine messenger RNA expression of progenitor cells (CD133) and factors that
      recruit them: vascular endothelial growth factor (VEGF-A), hypoxia-inducible
      factor 1alpha, matrix metalloproteinase 9 (MMP-9), and stromal cell-derived
      factor 1alpha. Angiopoietin 1 and 2, MMP-2, VEGF receptors, and neuropilin
      receptors were quantified using quantitative reverse transcription polymerase
      chain reaction. There was no difference in microvascular density, pericytic
      density, or endothelial proliferation between infiltrating lipomatosis and normal
      adipose tissue (P = 0.2). Expressions of VEGF-A, hypoxia-inducible factor 1alpha,
      stromal cell-derived factor 1alpha, angiopoietin 1 and 2, MMP-2 and -9, VEGF
      receptors 1 and 2, neuropilin receptors 1 and 2, and CD133 messenger RNA were not
      elevated compared to control fat (P = 0.1). Endothelial progenitor cells were not
      present in specimens of infiltrating lipomatosis. Infiltrating lipomatosis does
      not exhibit elevated angiogenic or vasculogenic factors compared to normal fat;
      the vasculature is stable. Neovascularization does not seem to play a role in the
      pathogenesis of this condition.

PMID- 22134294
TI  - Bilateral tonsillar adenoid cystic carcinoma.
AB  - Adenoid cystic carcinoma is a malignant epithelial tumor of the salivary glands.
      It accounts for less than 1% of all head and neck cancers and less than 10% of
      all salivary gland neoplasms. It shows slow and indolent growth rate, low
      probability of regional nodal metastases, high propensity for perineural
      invasion, multiple and/or delayed recurrences and high incidence of distant
      metastases. It is the most frequently encountered malignant tumor of the minor
      salivary glands. The oral cavity and the oropharynx are the most common sites
      followed by the parotid, submandibular gland, paranasal sinuses, larynx, trachea,
      and pharynx, in frequency order. In this report an adenoid cystic carcinoma of
      oral cavity localized in the left palatine tonsil and right peritonsillar tissue
      was presented.

PMID- 22134295
TI  - Eosinophilic granuloma:  resolution of lesion after biopsy.
AB  - Langerhans cell histiocytosis is a collective term used to describe a group of
      enigmatic proliferative disorders. Three disease variants include eosinophilic
      granuloma, Letterer-Siwe disease, and Hand-Schuller-Christian syndrome.
      Eosinophilic granuloma is reported to be the most benign type of the triad. In
      this report, a 7-year-old child with an eosinophilic granuloma of the left side
      of her mandible is presented. There was a painless, hard, tender mass arising
      from the left side of the molar region. Panoramic radiographs showed a
      radiolucent area at the molar region. The lesion was resolved 2 weeks after the
      biopsy. The 1.5 years of radiographic and clinical follow-up was satisfactory.

PMID- 22134296
TI  - Factitious panniculitis induced by cupping therapy.
AB  - Cupping therapy is an alternative medical procedure that has been widely
      performed in Asian countries to relieve pain. It is known that there is no
      complication to this therapy, so many non-health care professionals have
      performed this procedure. However, there have been few reports on complications,
      such as iron deficiency anemia, hemorrhagic bullae, kelloids, vasovagal syncope,
      and foreign body reactions. Masses associated with panniculitis induced by
      cupping are extremely rare, and they require a unique approach.A 56-year-old
      woman presented with a 10-month history of multiple masses in the posterior neck
      and right shoulder areas. The patient repeatedly attempted cupping therapy by
      herself, and multiple palpable masses developed in the posterior neck and right
      shoulder area where cupping therapy had been performed. The masses were enlarged
      by repeated cupping, and they decreased in size when cupping was stopped. Among
      all lesions, the 2 masses with tenderness were surgically excised. The remaining
      masses resolved after cupping therapy was ceased. When a patient with
      subcutaneous mass has a history of cupping or trace of cupping marks,
      panniculitis induced by cupping should be suspected. The lesion seems to
      spontaneously resolve unless they are repeatedly stimulated. However, surgical
      resection is considered in patients with infections or severe tenderness as a
      complication.

PMID- 22134297
TI  - Bilateral dermoid cysts of the upper lip.
AB  - Dermoid cysts are benign tumors found throughout the body. They are either
      congenital or acquired. Derived from both ectoderm and mesoderm, they are often
      diagnosed in childhood. Dermoid cysts of the head and neck region account for
      less than 10% of all dermoid cysts. The most common locations of the cysts are
      the periorbital region and the neck. We expose the case of a 47-year-old man who
      presented with bilateral dermoid cysts of the upper lip. Only 1 case of
      unilateral dermoid cyst of the upper lip is referenced in the literature. Authors
      report the first case of bilateral dermoid cysts and discuss its possible
      origins.

PMID- 22134298
TI  - Surgical technique of the transoral approach to remove a lipoma of the buccal fat
      pad.
AB  - BACKGROUND: In 1727, Heister (Compendium anatomicum. Altdorf, Guill, Koleshii:
      editio tertia 1727: 134, table VIII and figs. 36-37) described the buccal fat pad
      (BFP) as an independent anatomic structure of the face; in 1801, Bichat (Anatomie
      generale appliquee a la physiologie et a la medecine. Paris, France: Brosson,
      Gabon et Cie Libraires, 1801:60) reported his fatty histologic finding. According
      to the literature, several pathologic tumorous conditions can arise from BFP,
      such as lipoma, lipoblastomatosis, liposarcoma, hemangioma, arteriovenous
      malformation, and nodular fasciitis; all of which are rare. After a revision of
      the English literature performed through PubMed between 1948 and 2008, we found
      10 cases of lipomas arising from the BFP (7 cases are simple subtype, 2 are
      spindle cell lipoma, and 1 is fibrolipoma). The aims of this study were to
      introduce our clinical report of this rare pathologic entity, describe the
      surgical technique of the transoral approach, and discuss the potential pitfalls
      regarding the preoperative diagnosis and the close interrelation among the BFP,
      the facial buccal branches (FBBs), and the parotid duct (PD). CLINICAL REPORT: A
      43-year-old man was referred to the Maxillofacial Unit of the Novara Major
      Hospital with a 6-month history of a painless swelling in the right cheek.
      Clinical examination revealed a clearly visible, tender, slightly fluctuant mass,
      situated anterior to the masseter muscle and extended to the submandibular
      region. The patient underwent an ultrasound, a computed tomography, and a
      magnetic resonance imaging. Under general anesthesia with nasotracheal
      intubation, the patient underwent intraoral resection of BFP lipoma. DISCUSSION:
      The 2 major areas of discussion are the potential pitfall regarding the
      preoperative diagnosis and the close anatomic interrelation among the BFP, the
      FBB, and the PD. First, the spindle cell lipoma, one of the most common BFP
      lipoma variant, can be histologically and clinically similar to a well
      differentiated liposarcoma, which can be recurrent and metastatic. This issue
      warrants that a careful workup of the tumorous mass of the buccal space and a BFP
      origin must be considered in every situation. Finally, according to the recent
      literature, the anatomic variations of the interrelation between the FBB and the
      BFP are classified into 2 groups: (1) FBB passing lateral to the BFP and (2)
      branches crossing inside the BFP. The anatomic variations of the interrelation
      between the PD and the BFP are classified into 3 groups: (1) PD passing lateral
      to the BFP, (2) PD crossing deep to the BFP, and (3) PD running along the
      superior border of the BFP.

PMID- 22134299
TI  - Life-threatening complication of recurrent laryngeal nerve monitoring with EMG
      reinforced silicone ETT.
AB  - We present 2 cases with complication of herniation of a specially designed
      endotracheal tube (ETT) cuff used for laryngeal nerve monitoring during thyroid
      surgery. Abrupt and total blockage of ventilation has occurred at 35th and 40th
      minutes of general anesthesia. In an animal trachea, we showed that overinflated
      cuff may herniate and block ETT tip easily. A 25-mm upward movement of the ETT is
      found as a contributing factor to cuff herniation.In patients intubated with
      electromyographic reinforced ETT, any event suggesting sudden ventilation
      blockage should be managed initially by prompt deflation of the cuff. The cuff
      should be inflated at the minimal necessary volume, and operating room staff
      should pay maximum attention to the stability of endotracheal and breathing
      tubes.

PMID- 22134300
TI  - Lip lesions in a Brazilian population.
AB  - BACKGROUND: The lips represent one of the most important parts of the facial
      complex because of a large number and variety of injuries that may be related to
      this anatomic site such as inflammatory processes and benign and malignant
      tumors. The aim of this study was to describe the pathologic features of the lip
      lesions seen in a Brazilian outpatient service. METHODS: Data from 6231 samples
      of oral biopsies were retrieved from the files of 5 anatomic pathology services
      in Fortaleza, Brazil. After data have been collected, the lesions were separated
      in 3 groups: G1 (nonmalignant dysplastic lesions/malignant tumors), G2 (benign
      neoplasms), and G3 (reactive/inflammatory lesions). RESULTS: Analysis of the
      specimens for which an oral biopsy was performed yielded 1034 cases (16.6%)
      diagnosed on lip during the study period. From this total, 514 cases were in
      females and 520 were in males. Ages ranged from 2 to 96 years, with a global
      average of 40.1 years. The peak incidence of lip lesions in this study occurred
      in the fifth decade of life. The most common lesion in each group was squamous
      cell carcinoma (G1), hemangioma (G2), and mucocele (G3). Lower lip was the most
      affected region (65.9%). CONCLUSIONS: The largest number of cases represented
      nonmalignant conditions, which occurred mostly in the lower lip. In addition,
      malignancies increased significantly with the increase in age. Further studies
      are necessary for a better worldwide epidemiologic understanding about lip
      diseases.

PMID- 22134301
TI  - A salvage operation for flap compromise following internal jugular venous
      thrombosis.
AB  - The internal jugular vein (IJV) has been described as the optimal recipient
      vessel in oral and maxillofacial microsurgical rehabilitation and reconstruction.
      However, few studies have been reported on IJV thrombosis, which could compromise
      flap survival. In the current study, a case of flap vascular crisis following IJV
      thrombosis is presented, and salvage operation as a management strategy is
      discussed. Although rare, surgeons specializing in oral and maxillofacial
      microsurgical reconstruction should be aware of the possibility of the occurrence
      of this condition, considering early surgical intervention is critical.

PMID- 22134303
TI  - Bilateral rhinolithiasis.

PMID- 22134304
TI  - Unusual foreign body impaction in the palate:  plastic screw cap.

PMID- 22134305
TI  - Epidermal inclusion cyst of the larynx.
AB  - Epidermal inclusion cyst (EIC) is a benign cyst filled with keratin fibers, which
      can develop in any part of the body. It is commonly seen in the skin, especially
      on the face, scalp, neck, and trunk, and has the tendency to slowly grow toward
      deeper epidermis parts and to cause cystic expansion. Epidermal inclusion cysts
      are not common in mucosal sites such as the larynx; however, these can arise
      owing to squamous metaplasia of the glands. We present a 52-year-old man with a
      laryngeal EIC. This is a very rare case in the literature of EIC in the larynx.

PMID- 22134306
TI  - Unusual split fracture of the mandible.
AB  - Mandibular fracture is a common injury and generally treated with or without
      surgery depending on the case. Diagnosing mandibular fracture may be difficult
      because of its location and anatomic characteristics. This article presents a
      case of an unusual split mandibular fracture after an episode of seizure in a
      patient with epilepsy. This fracture was missed on routine radiographs; however,
      it was visualized by three-dimensional computed tomography (TCT). The TCT is
      crucial and should be mandatory for all suspected mandibular fractures instead of
      routine radiography. The diagnostic efficacies of panoramic radiographs,
      digitized radiographs, and TCT scans are discussed for the diagnosis of
      mandibular fractures in this case report.

PMID- 22134307
TI  - Myositis ossificans circumscripta involving bilateral masticatory muscles.
AB  - Myositis ossificans (MO), as its name implies, is ossification and bone formation
      within a muscle. Pathogenesis is not all clear, but trauma is universally
      recognized as a trigger event. Myositis ossificans can be divided into 2
      classifications: MO progressiva and MO traumatica. When it affects the muscles of
      mastication, it causes severe trismus. This rare disorder and its limited
      treatment options can potentially have debilitating effects to the patient's
      normal oral functioning and health. A computed tomographic scan and panoramic
      radiographs are essential diagnostic aids for evaluating conditions such as MO.
      Myositis ossificans can be one of the causes of extra-articular temporomandibular
      joint ankylosis. Surgical excision of the ossification is the main treatment
      modality. This is a case report of a patient who developed MO of the muscles of
      mastication.

PMID- 22134308
TI  - Temporomandibular joint vibration before and after exercises and occlusal
      splints.
AB  - Temporomandibular joint (TMJ) sounds are frequent in patients. The aim of this
      study was to analyze patients with clicking at the end of opening and at the
      beginning of closing their mouths treated by muscular exercises through chewing
      and by occlusal splints. Fifteen patients with clinically verified clicking and
      TMJ and 15 patients without sounds were selected by the Research Diagnostic
      Criteria for Temporomandibular Disorders. They were submitted to
      electrovibratography at consultation and 60 and 120 days of treatment by occlusal
      splints and exercises. Patients demonstrated significant reduction of TMJ sounds
      after treatment, but vibration intensity was not similar with that of the control
      group after 120 days.

PMID- 22134309
TI  - Nasal septal hematoma and abscess in children.
AB  - OBJECTIVE: The objective of the study was to evaluate the demographic factors,
      trauma type, treatment, and long-term results in patients with nasal septal
      hematoma (NSH) and nasal septal abscess (NSA). METHODS: Between the years 2006
      and 2010, subjects who received a diagnosis of NSA and NSH were included for the
      study. Demographic data, the surgical findings, and long term follow-up results
      were recorded. RESULTS: Twenty-nine subjects were identified. Eleven subjects had
      a diagnosis of NSA, whereas 19 subjects were identified as having NSH. Eighteen
      subjects (62.1%) were male, whereas the remaining 11 subjects (38.9%) were
      female. Mean age of the subjects was 7.79 +/- 3.99 years. The etiologies were
      fall in 26 subjects (89.6%) and blow in 3 subjects (10.4%). Four subjects were
      previously examined by a physician. In 9 subjects (31.1%), radiologic and
      clinical evidence of nasal fracture exists. Eighteen (72%) of 29 subjects
      experienced sequelae. No significant difference exists for clinical properties,
      demographic data, etiology, and so on, except mean duration; P > 0.05. Mean
      duration was significantly high in the NSA group than in the NSH group (8.40 +/-
      8.46 days vs 3.58 +/- 3.64 days, P = 0.025). CONCLUSIONS: This study demonstrated
      that both NSH and NSA have similar properties for demographic data, etiology, and
      sequelae.

PMID- 22134310
TI  - Etiology and patterns of facial lacerations and their possible association with
      underlying maxillofacial fractures.
AB  - BACKGROUND: This study was designed to analyze the etiology and patterns of soft
      tissue facial lacerations associated with maxillofacial fractures and to identify
      associations between facial lacerations and underlying fractures. METHODS: Of
      1960 patients who had been admitted for maxillofacial fractures between 2001 and
      2010, only patients with complete clinical records presenting with facial
      lacerations were considered for this study. Facial lacerations were classified
      according to the MCFONTZL system. RESULTS: Of the 1960 patients admitted with
      maxillofacial fractures, 637 had 836 associated facial lacerations. Motor vehicle
      accidents and falls were responsible for most injuries to patients with facial
      lacerations. According to etiology, fractures resulting from work-related
      accidents more frequently produced associated lacerations.For all causes of
      injury, more facial lacerations were observed over the "T" area formed by the
      upper orbit and forehead, nose, upper and lower lips, and chin. Lacerations and
      maxillofacial fractures were more frequently localized to the middle third of the
      face, followed by the inferior third.There was a strong association between
      lacerations and fractures in the chin region, considering both symphyseal and
      parasymphyseal fractures (direct trauma) and condylar fractures (indirect
      trauma). CONCLUSIONS: An association between facial lacerations and underlying
      maxillofacial fractures was observed, particularly in the inferior orbital area
      and over the zygoma, mandible, and chin.

PMID- 22134311
TI  - Solitary plasmacytoma of the jaw.
AB  - BACKGROUND: There is a lack of consensus on the appropriate management of
      solitary plasmacytoma (SP) of the jaw. The aim of the present investigation was
      to provide scientific evidence for the optimal management of this disease through
      a systematic literature review. METHODS: The included articles are published in
      English from 1948 to March 2011 and describe the population affected by SP of the
      jaw with site, clinical and radiographic features, special findings, initial
      diagnosis, treatment, and follow-up. RESULTS: Fifty cases of SP of the jaw were
      identified. It typically presents as a single osteolytic lesion with no
      plasmocytosis involvement of bone marrow. Long bones and vertebrae are the most
      common sites of SP. Rarely, it involves the jaw occurring in only 4% of cases,
      mainly in the bone marrow-rich areas, angulus and ramus. Solitary plasmacytoma of
      the jaw has a worse prognosis than multiple myeloma (MM), and in half of the
      cases, it evolves in MM. CONCLUSIONS: Because SP of bones is an uncommon tumor
      that rarely involves the jaws, through this article we emphasize early diagnosis
      and appropriate management to avoid progression to MM.

PMID- 22134312
TI  - Preauricular transcondylar approach for basal cell adenoma of parotid coexist
      with ganglion cyst of the ipsilateral temporomandibular joint.
AB  - The concurrence of 2 independent neoplasias in the ipsilateral parotid and the
      temporomandibular joint (TMJ) region was infrequently reported. In this article,
      we present a unique case characterized by the coexistence of a rare salivary
      gland tumor, basal cell adenoma, of the parotid gland with a ganglion cyst in the
      ipsilateral TMJ region. A special surgical procedure was also presented here
      using a modified preauricular incision and transcondylar approach for
      extracapsular dissection of both lesions. Previously published literature are
      about the traditional treatment of benign parotid tumors using partial or total
      parotidectomy with the preservation of facial nerve mainly via an S-shaped
      submandibular incision and approach. Here, for the first time, a special surgical
      method using preauricular transcondylar approach for this unique case of
      synchronous occurrence of parotid tumor and TMJ cyst is reported.

PMID- 22134314
TI  - Cavernous hemangioma of the accessory parotid gland.
AB  - We report a rare case of a hemangioma arising from the accessory parotid gland.
      The patient, a 45-year-old woman, complained of a right midcheek mass. Magnetic
      resonance imaging showed a well-defined mass located in the right buccal space,
      anterior to the masseter muscle, and adjacent to the Stensen duct. The mass had
      high T2-weighted signal intensity and showed strong patchy enhancement with
      gadolinium. This mass was surrounded by a common capsule with the accessory
      parotid gland. These findings indicated a hemangioma originating from the
      accessory parotid gland. The mass was completely removed by an intraoral approach
      without postoperative facial palsy, skin deformity, and difficulty in secreting
      saliva. Histologic examination of the tumor revealed multiple, thin-walled, and
      dilated blood vessels, confirming the diagnosis of a cavernous hemangioma.
      Magnetic resonance imaging was extremely useful in diagnosing the mass as a
      hemangioma before surgery, clarifying relationships between the mass and adjacent
      structures and determining the surgical approach to the mass.

PMID- 22134313
TI  - Giant cementoblastoma of the impacted mandibular incisor.
AB  - The cementoblastoma is a relatively rare type of all odontogenic tumors. The
      incisor and impacted or unerupted tooth involvement by a cementoblastoma is
      extremely rare. We present a case report of a giant cementoblastoma that involved
      an impacted mandibular incisor.

PMID- 22134315
TI  - Periosteal ossification from the vascular pedicle of a free fibular flap.
AB  - BACKGROUND: Free fibular flap is commonly used in mandibular reconstruction. In
      some cases, to obtain a longer vascular pedicle, the peroneal artery and vein are
      stripped of the proximal fibula with its periosteum. PATIENT: A 17-year-old
      patient evaluated with fibromyxoma of the mandible underwent excision of the
      tumor and reconstruction with a 6-cm free fibular flap. To obtain a longer
      pedicle, the peroneal artery and vein were stripped of the proximal fibula
      together with the periosteum. The recovery was uneventful. In his 6-month follow
      up, there was a hard palpable stick-like mass (4 * 0.5 cm) 3 cm below the
      mandible. In the panoramic mandibular radiography, there was a radiopaque mass
      and ossification in the same location. The patient had no complaints, and no
      further treatment was done. DISCUSSION: Periosteal ossification from the pedicle
      of the free fibular flap is a very rare phenomenon. However, because of the
      capacity of the periosteum to regenerate a new bone, it can be seen especially in
      younger patients. This can be prevented by a more careful dissection of the
      vascular pedicle from the bone and the periosteum. In cases where the primary
      disease is a tumor, it can be confused with recurrence. Depending on where the
      pedicle and the ossification are, it can give rise to symptoms or be totally
      asymptomatic.

PMID- 22134316
TI  - Progressive dysphagia in an elderly male.
AB  - Dysphagia can result from a variety of causes, including central nervous and
      peripheral nervous system, myogenic, and structural disorders. A 76-year-old man
      underwent anterior cervical disketomy and fusion 10 years ago, with progressive
      dysphagia noted 2 years ago. Endoscopy showed an oropharyngeal tumor, and lateral
      plain film evaluation of the neck revealed a cervical plate extrusion. Removal of
      the instrumentation and tumor with primary closure of the pharyngeal perforation
      was performed, and dysphagia was resolved postoperatively. We report the case of
      an unusual presentation in the pharynx. We should not neglect this rare
      diagnosis, because it can progress to a life-threatening outcome.

PMID- 22134317
TI  - Fracture of the coronoid process, sphenoid bone, zygoma, and zygomatic arch after
      a firearm injury.
AB  - A rare case of fracture of the coronoid process, sphenoid bone, zygoma, and
      zygomatic arch caused by a firearm is described. A 25-year-old man was hit in the
      face with a bullet, resulting in restricted mouth opening, difficulty chewing,
      and pain when opening the mouth. The clinical examination revealed a perforating
      wound in the right parotid region. A computed tomographic scan revealed a
      comminuted fracture of the left coronoid process with the bullet stopping in the
      intact left coronoid process. Treatment was bilateral coronoidectomy associated
      with speech therapy and was successful. Details of the clinical signs, computed
      tomography, treatment, and follow-up are presented.

PMID- 22134318
TI  - Massive congenital kaposiform hemangioendothelioma of the eyelid in a neonate.
AB  - BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare and aggressive
      vascular tumor of infancy and childhood. It is associated with the development of
      Kasabach-Merritt syndrome, a life-threatening consumptive thrombocytopenia. We
      report an interesting case of a massive periorbital congenital KHE in a neonate
      to raise awareness of this aggressive diagnosis. METHODS: A male neonate
      presented with a large congenital mass of the lower eyelid. To prevent
      development of amblyopia, this mass was surgically excised on the sixth day of
      life. RESULTS: Histologic investigation demonstrated spindle-shaped endothelial
      cells with surrounding crescentic vessels, which were GLUT-1 receptor-negative
      and D2-40 receptor-positive, consistent with KHE. Surgical excision of the
      periorbital KHE successfully cleared the neonate's visual axis. At 1 year of
      follow-up, there was no evidence of tumor recurrence, and visual development was
      progressing normally. A pleasing surgical result was achieved without periorbital
      distortion. CONCLUSIONS: Pediatric vascular tumors have historically been wrought
      with diagnostic confusion. With recent advances in immunohistochemistry, this
      previously uncharacterized group of tumors has been differentiated into multiple
      distinct clinical entities. Accurate and timely diagnosis is paramount because
      these tumors vary greatly in their clinical behavior, prognosis, and recommended
      treatment. Surgical excision is preferred and necessary in a neonate with visual
      access obstruction to prevent amblyopia and irreversible blindness.

PMID- 22134319
TI  - Upper blepharoplasty approach to frontozygomatic dermoid cysts.
AB  - OBJECTIVES: Dermoid cysts are common periorbital lesions in children. Traditional
      surgical approaches have included incisions over the mass; above, below, or
      through the brow; and parallel to the superior orbital rim and the Lynch
      incision, as well as lateral canthotomy. We aimed to present experience of Alder
      Hey Children's Hospital on frontozygomatic dermoid removal through a
      blepharoplasty incision. In this article, we also aimed to review the current
      literature, describe the operative technique clearly, and offer reasonable
      explanations for the operative choices made based on our experience of the
      clinical anatomy and pathology. METHODS: Thirty-four children were operated on
      (19 girls and 15 boys), aged 1 to 11 years, between 2005 and 2008. The lesions
      were left sided in 14 patients and right sided in 20 patients. Preoperative
      computed tomographic/magnetic resonance imaging scan was generally not used,
      except in cases where the cyst was more than 1 cm away from the brow margin.
      RESULTS: All cysts were completely excised. At surgery, all cysts were adherent
      to the periosteum, and 3 were subperiosteal. None extended through the bone into
      the orbit. The average operating time was 30 minutes. The average follow-up
      duration was 1 year. The only complications were early mechanical ptosis in 3
      children, which completely resolved; the majority had an uneventful postoperative
      course. There were no recurrences, and in all patients, scar camouflage was
      described as excellent. CONCLUSIONS: This interesting and extremely effective
      technique provides excellent scar camouflage with no lid or ocular dysfunction.

PMID- 22134320
TI  - Intraosseous mandibular venous malformation.
AB  - Intraosseous venous malformations are rare benign lesions that account for
      approximately 0.5% to 1% of all osseous tumors. Involvement of the facial
      skeleton is rather uncommon, with the mandible and maxilla most frequently
      involved. In the current study, we report a case of an intraosseous venous
      malformation in a 52-year-old male patient with a history of mandibular
      keratocystic odontogenic tumor. The patient presented with an asymptomatic bony
      lesion in the mandible. Treatment involved surgical excision. Histopathologic
      examination of the excised specimen revealed an intraosseous venous malformation.
      Twelve months postoperatively, there was no evidence of recurrence.

PMID- 22134321
TI  - Anophthalmia:  an uncommon manifestation of neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF-1) is an autosomal dominant, multisystem disorder,
      affecting approximately 1 of 3500 people. Ocular disorders, such as Lisch
      nodules, optic gliomas, and anterior segment defects, are typical with clinical
      presentation. Anophthalmia, as a rare eye malformation, has never been reported
      in patients with NF-1. We report a 27-year-old patient in whom clinical
      manifestations of cafe au lait spots, neurofibromas, osseous orbital dysplasia,
      and anophthalmia were observed. The diagnosis of NF-1 was made, according to
      clinical course and brain computed tomography and magnetic resonance imaging.
      Because the patient refused aggressive management approaches, she was managed
      conservatively and is well on follow-up. We suggest that patients presenting with
      anophthalmia need serious evaluation and that NF-1 needs to be considered in the
      differential diagnosis.

PMID- 22134322
TI  - Frontal sinus agenesis using computed tomography.
AB  - In adults, paranasal sinus agenesis is an uncommon anomaly that appears mainly in
      the frontal sinus. The aim of this study was to investigate the prevalence of
      agenesis of the frontal sinus using computed tomography in a population of
      Iranian individuals. Computed tomographic scans in the axial and coronal planes
      of the frontal sinus of 565 patients were examined for evidence of the absence of
      the frontal sinus. A bilateral agenesis of the frontal sinus was seen in 8.32% of
      cases, and unilateral absence of the frontal sinus was observed in 5.66%. The
      information provided in the current study is useful for some craniofacial
      surgeries and improves the anthropometric knowledge of humanity. There are
      limited studies on agenesis of the frontal sinus in the literature, but comparing
      our findings with the available data, there were differences regarding the
      incidence of this condition. This may be related to geographic and racial
      features. More studies on other population are required.

PMID- 22134323
TI  - Pleomorphic sarcoma of the neck.
AB  - The case of a 68-year-old woman who had a big mass (plemorphic sarcoma) in the
      back of the neck and treated with surgical resection is presented. Primary
      malignant fibrous histiocytoma of the neck is rare, although it is among the most
      common soft tissue sarcomas in adults. The primary mode of therapy is surgery,
      but because of high rates of local and distant recurrence radiation, therapy
      should be added to decrease local relapse. Malignant fibrous histiocytoma is
      discussed with a brief literature review.

PMID- 22134324
TI  - Lower eyelid surgery for lagophthalmos in Mobius and Poland-Mobius syndromes.
AB  - BACKGROUND: Patients with Mobius and Poland-Mobius syndromes may experience
      paralytic lagophthalmos. METHODS: This is a retrospective interventional case
      series. We report 1 case of Mobius syndrome and 2 cases of Poland-Mobius
      syndrome, wherein patients underwent lower blepharoplasty for lagophthalmos with
      2 different surgical techniques. RESULTS: Two patients with Poland-Mobius
      syndrome presenting with bilateral lower eyelid entropion and paralytic
      lagophthalmos underwent lower eyelid elongation using right auricular cartilage
      via a transcutaneous approach. One patient with Mobius syndrome presenting with
      monolateral lower eyelid ectropion and lagophthalmos underwent lower eyelid
      elongation with Tessier cheek rotation flap. In all cases, lagophthalmos
      disappeared, and no complications were reported after a mean follow-up period of
      19.6 months. CONCLUSIONS: A good functional correction of lagophthalmos was
      obtained at long-term follow-up with 2 different surgical techniques. In patients
      with Mobius and Poland-Mobius syndromes, correction of lagophthalmos should be
      rapidly undertaken to prevent consequences of exposure keratopathy.

PMID- 22134325
TI  - Castleman disease as a giant parapharyngeal mass presenting with dysphagia.
AB  - A giant unilateral parapharyngeal mass from the skull base to the vocal folds is
      presented in this case. A 20-year-old man experiencing dysphagia for 4 years was
      admitted, and his magnetic resonance imaging and computed tomographic scans
      showed a giant parapharyngeal ellipsoid mass from the left jugular foramen to the
      vocal folds. Its craniocaudal length was 9 cm. The left internal carotid artery
      was lateralized, and posterior glottic airway was narrowed by the mass. In
      digital subtraction angiography, 2 aberrant branches of the internal carotid
      artery were going inside the mass. After the excision, histopathologic evaluation
      showed the diagnosis, Castleman disease. This is the first case in literature
      presenting with the only symptom of dysphagia.

PMID- 22134326
TI  - Myiasis in palate by Cochliomyia hominivorax.
AB  - Myiasis is the infestation of tissues and organs of animals and humans caused by
      the larvae of certain dipteran flies. It is more common in undeveloped and
      tropical countries and usually affects elderly patients, persons who are sick,
      and patients with mental illness. Oral myiasis is a rare pathologic condition and
      a risk to the patient's life because of its great destructive potential.
      Therefore, appropriate treatment is necessary. This article aimed to report a
      case of myiasis caused by Cochliomyia hominivorax in the palate of a patient with
      primary progressive aphasia, which was successfully treated through mechanical
      removal of larvae plus administration of ivermectin.

PMID- 22134327
TI  - Upper lip prosthesis retained to a palatal obturator.
AB  - In cases of total or partial maxillectomies, the prosthetic rehabilitation is an
      effective alternative to minimize the sequelae left by surgical resection. The
      present study reports a clinical case of a 52-year-old patient who underwent
      partial maxillectomy, with upper lip involvement. The oronasal communication,
      resultant from surgical resection, did not allow the patient to return to her
      normal social life. Besides, the upper lip partial resection damaged her face's
      aesthetics. The proposed treatment was the confection of an upper lip prosthesis
      retained by a palatal obturator. The prosthesis insertion restored the patient's
      facial aesthetics, contributing not only to function, but also to psychosocial
      adaptation.

PMID- 22134328
TI  - High-grade mucoepidermoid carcinoma of the larynx.
AB  - Laryngeal mucoepidermoid carcinoma is rare. Approximately 85 cases have been
      reported in the literature. There is no standardized treatment because of the
      rarity of the disease. A case of a 55-year-old man with laryngeal mucoepidermoid
      carcinoma, who was treated with total laryngectomy and postoperative
      radiotherapy, is presented, and current literature is reviewed.

PMID- 22134329
TI  - Large radicular cyst in the maxillary sinus.
AB  - Radicular cysts (RCs) are the most common inflammatory jaw cystic lesions that
      occur infected and necrotic in teeth pulps. They account for more than 50% of all
      odontogenic cysts. Radicular cysts cause slowly progressive painless swelling.
      There are no symptoms until they become large. Enucleating the cyst is
      recommended with primary treatment. Here we describe a patient with a large RC
      with maxillary sinus involvement who underwent an endonasal endoscopic approach
      for complete resection. In conclusion, the endonasal endoscopic approach should
      be kept in mind for the resection of RC with maxillary sinus involvement because
      of its minimally invasive characteristics.

PMID- 22134330
TI  - Solitary infantile myofibroma of the skull.
AB  - Infantile myofibromatosis is a proliferative disorder characterized by the
      development of single or multiple nodular lesions in the soft tissue, skeleton,
      and internal organs. These tumors can occur at any anatomic site, but in one
      third of the cases, the head and neck region is involved. Here, we report a case
      of an infantile myofibroma occurring in a 7-year-old girl presented as a solitary
      lesion in the head and neck area. The clinical heterogeneity and the misleading
      histopathologic appearances may render the diagnosis difficult. Usually,
      treatment of choice is surgical removal of the tumor; however, the low rate of
      recurrence and the possibility of spontaneous regression may lead to conservative
      surgery or therapeutic abstention.

PMID- 22134331
TI  - H2 storage and CO2 capture on a nanoscale metal organic framework with high
      thermal stability.
AB  - A nanoscale aluminium-based metal organic framework (NMOF) with high thermal
      stability has been synthesized, which shows high H(2) and CO(2) uptake capacities
      and an excellent selectivity for CO(2) over N(2) and O(2).

PMID- 22134332
TI  - Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is
      associated with a poor prognosis in advanced esophageal cancer patients.
AB  - The HLA class I antigen processing machinery (APM) plays a crucial role in the
      anticancer immune response. The aim of this study was to assess the clinical
      significance of APM components in esophageal cancer. A total of 11 esophageal
      cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM
      components. There was a different expression pattern among cancer cell lines for
      HLA class I heavy chain (HLA-HC), beta2 microglobulin, Tapasin, TAP-1, TAP-2, LMP
      7 and LMP-10. Immunohistochemical staining utilizing a tissue microarray method
      for HLA class I APM expression showing different expression patterns among cell
      lines was performed for 95 surgical specimens from patients with esophageal
      cancer. Prognostic factors were the down-regulation of HLA-HC, and the up
      regulation of beta2 microglobulin and TAP-1 in the cancer tissues. Multivariate
      analysis using a Cox regression model indicated that the down-regulation of HLA
      HC, and up-regulation of TAP-1 in cancer tissues are independent, unfavorable
      prognostic factors (hazard ratio, 2.361 and 2.297; P=0.0141 and 0.0145,
      respectively). Although there was no significant difference in survival for
      selected p-stage I and II patients (n=54) in all APM components, only down
      regulation of HLA-HC was an unfavorable prognostic factor by a Cox regression
      model for selected p-stage III and IV patients (n=41). In conclusion, the current
      results suggest that the down-regulation of HLA-HC in tumors is especially
      associated with a poor prognosis among advanced esophageal cancer patients.

PMID- 22134333
TI  - iLoc-Hum: using the accumulation-label scale to predict subcellular locations of
      human proteins with both single and multiple sites.
AB  - Although numerous efforts have been made for predicting the subcellular locations
      of proteins based on their sequence information, it still remains as a
      challenging problem, particularly when query proteins may have the multiplex
      character, i.e., they simultaneously exist, or move between, two or more
      different subcellular location sites. Most of the existing methods were
      established on the assumption: a protein has one, and only one, subcellular
      location. Actually, recent evidence has indicated an increasing number of human
      proteins having multiple subcellular locations. This kind of multiplex proteins
      should not be ignored because they may bear some special biological functions
      worthy of our attention. Based on the accumulation-label scale, a new predictor,
      called iLoc-Hum, was developed for identifying the subcellular localization of
      human proteins with both single and multiple location sites. As a demonstration,
      the jackknife cross-validation was performed with iLoc-Hum on a benchmark dataset
      of human proteins that covers the following 14 location sites: centrosome,
      cytoplasm, cytoskeleton, endoplasmic reticulum, endosome, extracellular, Golgi
      apparatus, lysosome, microsome, mitochondrion, nucleus, peroxisome, plasma
      membrane, and synapse, where some proteins belong to two, three or four locations
      but none has 25% or higher pairwise sequence identity to any other in the same
      subset. For such a complicated and stringent system, the overall success rate
      achieved by iLoc-Hum was 76%, which is remarkably higher than that by any of the
      existing predictors that also have the capacity to deal with this kind of system.
      Further comparisons were also made via two independent datasets; all indicated
      that the success rates by iLoc-Hum were even more significantly higher than its
      counterparts. As a user-friendly web-server, iLoc-Hum is freely accessible to the
      public at  or . For the convenience of most experimental scientists, a step-by
      step guide is provided on how to use the web-server to get the desired results by
      choosing either a straightforward submission or a batch submission, without the
      need to follow the complicated mathematical equations involved.

PMID- 22134335
TI  - A square-pyramidal organochromium(V) compound.
AB  - The mononuclear, five-coordinate organochromium(V) compound
      [NBu(4)][CrO(C(6)F(5))(4)] (1) has been obtained as a dark red solid in moderate
      yield by treatment of the homoleptic organochromium(III) derivative
      [NBu(4)](2)[Cr(C(6)F(5))(5)] with NO[BF(4)] in CH(2)Cl(2) solution under an
      oxygen atmosphere. The Cr(V) centre in the [CrO(C(6)F(5))(4)](-) anion shows a
      square-pyramidal geometry with the four C(6)F(5) groups in the basal positions
      and the oxo ligand in the apical one (X-ray). The short Cr-O distance (153.8(2)
      pm) suggests a high degree of triple bond character for the chromyl unit. The EPR
      spectrum of 1 in solution shows an isotropic signal with g(iso) = 1.995(1) and a
      rich hyperfine structure due to coupling with the (53)Cr isotope [a(Cr) =
      46.95(4) MHz] as well as with the ortho-F and meta-F substituents of the C(6)F(5)
      rings [a(F) = 4.20(2) MHz and a'(F) = 2.12(2) MHz] in keeping with the presence
      of non-interacting, fast tumbling, paramagnetic [CrO(C(6)F(5))(4)](-) units
      (d(1)). In the solid state, however, both the microscopic (EPR) and macroscopic
      magnetic properties (isothermal magnetisation and thermal dependence of the
      magnetic susceptibility) suggest the existence of weak ferromagnetic interactions
      with T(C) = 0.20(2) K. Such magnetic interactions may probably be favoured by pi
      interactions between C(6)F(5) rings of neighbour [CrO(C(6)F(5))(4)](-) units in
      the crystal.

PMID- 22134336
TI  - A new efficient iron catalyst for olefin epoxidation with hydrogen peroxide.
AB  - A new aminopyridine ligand derived from bipiperidine (the product of full
      reduction of bipyridine, bipy) coordinates to iron(II) in a cis-alpha fashion,
      yielding a new selective catalyst for olefin epoxidation with H(2)O(2) under
      limiting substrate conditions.

PMID- 22134337
TI  - Patterns of depressive symptoms and antidepressant use among women survivors of
      intimate partner violence.
AB  - PURPOSE: One of the primary mental health responses of women experiencing
      intimate partner violence (IPV) is depression, yet little is known about the
      mental health and antidepressant use of women in the period after leaving an
      abusive partner. We investigate patterns of antidepressant use and depressive
      symptoms by various social indicators (parenting status, socioeconomic status,
      severity of abuse and disclosure of abuse). Second, we examine whether variation
      in antidepressant use is explained by higher rates of depression diagnoses and/or
      depressive symptoms, taking these social indicators into consideration. METHODS:
      We examine data from the Women's Health Effects Study, a community sample of 309
      Canadian women who have recently left an abusive partner. RESULTS: Bivariate
      results reveal that over 80% of women with elevated depressive symptoms are
      without diagnosis and antidepressant medication. Multivariate analyses show that
      antidepressant use is predicted by an indicator of economic disadvantage, with
      women who receive social assistance or disability benefits being more likely to
      report elevated antidepressant use, controlling for both depressive symptoms and
      depression diagnoses. CONCLUSIONS: Documenting and explaining depressive symptoms
      and antidepressant use among IPV survivors provides insight into one of many
      possible treatment options available to women with depression, and sheds light on
      potential health disparities among this subgroup of the population.

PMID- 22134338
TI  - Towards antibiofouling ultrafiltration membranes by blending silver containing
      surface modifying macromolecules.
AB  - The innovative design and synthesis of membranes with silver incorporated
      surfaces open up new avenues for applied basic functions.

PMID- 22134339
TI  - Dissecting the HIV-specific immune response:  a systems biology approach.
AB  - PURPOSE OF REVIEW: Several unique HIV-infected or HIV-resistant cohorts have been
      studied over the years to try and delineate the correlates of protection.
      Although several mechanisms have been put forward, studies aiming to integrate
      the different mechanisms into a comprehensive model are still lacking. Current
      systems biology approaches emphasize the importance of unifying independent
      datasets, provide tools that facilitate hypothesis formulation and testing, and
      direct us toward uncovering novel therapeutic targets by defining molecular
      networks perturbed during disease. This review will focus on the current findings
      that utilized systems biology techniques in order to identify correlates of
      protection from HIV disease progression and resistance to infection in unique
      cohorts of individuals as well as in nonhuman primate models of SIV infection.
      RECENT FINDINGS: Using systems biology technologies and data analysis tools, the
      studies described herein have found that pathways implicated in survival, cell
      cycling, inflammation, and oxidative stress work in unison to limit pathology
      caused by chronic immune activation. This situation favors the survival of
      effector lymphocytes and limits the dissemination of viral particles in HIV elite
      controllers, exposed-uninfected individuals, and natural hosts of SIV infection.
      SUMMARY: Systems and computational biology tools have clearly expanded our
      understanding of HIV pathogenesis by unifying independent observations and by
      giving us novel molecular targets to pursue. These molecular signatures have the
      potential to uncover correlates of protection in HIV disease and, in the era of
      personalized medicine, to determine predictive signatures of treatment efficacy
      and/or failure.

PMID- 22134340
TI  - Profiling immunity to HIV vaccines with systems biology.
AB  - PURPOSE OF REVIEW: The recent modest success of the RV144 HIV vaccine trial in
      Thailand has shown that development of an HIV vaccine is possible. Designing a
      vaccine that achieves better protection, however, will require a more complete
      understanding of vaccine mechanisms of action and correlates of protection.
      Systems biology approaches enable integration of large datasets from a variety of
      assays and offer new approaches to understanding how vaccine-induced immune
      responses are coordinately regulated. In this review, we discuss the recent
      advances in clinical trial design, specimen collection, and assay standardization
      that will generate datasets for systems analyses of immune responses to HIV
      vaccines. RECENT FINDINGS: Several recently published HIV vaccine trials have
      shown that different HIV vaccine prime/boost combinations can greatly affect the
      immune response generated, but mechanistic insights into their modes of action
      are lacking. Novel systems biology studies of efficacious, licensed vaccines
      provide a new template for analysis of HIV vaccines. To generate datasets
      appropriate for systems analysis, current HIV vaccine clinical trials are
      undergoing design modifications and increased standardization of specimen
      collection and immune response assays. SUMMARY: Systems biology approaches to HIV
      vaccine evaluation are driving new methods of HIV vaccine immune response
      profiling in clinical trials and will hopefully lead to new improved HIV vaccines
      in the near future.

PMID- 22134342
TI  - Systems biology of natural simian immunodeficiency virus infections.
AB  - PURPOSE OF REVIEW: A key factor driving AIDS-associated immunopathogenesis is
      chronic immune activation. Simian immunodeficiency virus (SIV) infection of
      African natural host species leads to high viremia, but low immune activation and
      absence of disease. Considerable progress in our understanding of pathological
      immune activation has come from comparative studies of SIV infection in
      pathogenic Asian macaque species and natural hosts. The focus of this review is
      to highlight recent work on the natural host model using high-throughput
      genomics. RECENT FINDINGS: Several groups have independently conducted microarray
      gene expression profiling comparing in-vivo SIV infection in natural and non
      natural hosts. A consistent finding between these studies is that both pathogenic
      SIV infection of macaques and nonpathogenic infections of natural hosts have
      strong induction of interferon-stimulated genes (ISGs) early on, but a key
      difference was that natural hosts down-modulated the interferon response rapidly
      after acute infection. The development of new genome-based resources for further
      study of the natural host model is discussed. SUMMARY: Initial efforts using high
      throughput biology to study SIV infection of natural hosts have effectively
      identified the ability of natural hosts to resolve interferon responses and
      immune activation. Further application of 'omic-based technologies coupled with
      integrative systems-based analysis should continue to yield progress.

PMID- 22134343
TI  - Systems biology in understanding HIV pathogenesis and guiding vaccine
      development.

PMID- 22134341
TI  - Acquired transcriptional programming in functional and exhausted virus-specific
      CD8 T cells.
AB  - PURPOSE OF REVIEW: Failure to control viral infections such as HIV results in T
      cell receptor (TCR) and inhibitory receptor driven exhaustion of antigen-specific
      T cells. Persistent signaling by these receptors during chronic viral infection
      sculpts the transcriptional regulatory programs of virus-specific T cells. The
      resulting gene expression profile is tailored to temper the potentially damaging
      effector functions of cytotoxic T cells and adapt them to an antigen-rich and
      inflammation-rich environment. Here we review recent studies investigating
      mechanisms of transcriptional regulation of effector, functional memory, and
      exhausted T-cell functions during acute versus chronic infections. RECENT
      FINDINGS: Patterns of gene expression in virus-specific CD8 T cells are a result
      of a combination of pro and inhibitory signals from antigen presentation (TCR
      mediated) and co-inhibitory receptor ligation (PD-1, 2B4). Further, memory
      specific transcriptional regulation of 2B4 expression and signaling impose a self
      limiting secondary effector response to a prolonged viral infection.
      Additionally, differentiation of functional memory CD8 T cells is coupled with
      acquisition of a repressive epigenetic program for PD-1 expression. However,
      chronic infection provides a signal that blocks the acquisition of these
      epigenetic modifications reinforcing the suppression of cytotoxic lymphocyte
      (CTL) functions in exhausted cells. SUMMARY: Current findings suggest that the
      mechanism(s) that delineate functional memory versus exhaustion are coupled with
      acquisition of transcriptional programs at the effector stage of differentiation,
      reinforced by cessation or persistence of TCR signaling.

PMID- 22134344
TI  - [Follicular conjunctivitis of unknown origin].
AB  - A 40-year-old female chemical laboratory assistant presented at our clinic with
      chronic conjunctivitis of 4 years' standing. We initially misdiagnosed her
      symptoms as giant papillary conjunctivitis. Topical treatment failed to produce
      an improvement and a biopsy was performed. Histopathological analysis showed
      bilateral follicular lymphoma, a subtype of the B-cell non-Hodgkin lymphoma. The
      patient was referred for radiotherapy. At follow-up 18 months later the patient
      was symptom-free.

PMID- 22134345
TI  - [Choroidal tumor with exsudative retinal detachment?].
AB  - We present the case of a 41-year-old female patient with acute onset of
      nyctalopia, xanthopsia and impairment of visual field. The ophthalmologic
      examination revealed peripheral choroidal elevation with accompanying retinal
      detachment. Due to the the presence of a nanophthalmic eye without any evidence
      of inflammation or malignant growth, the diagnosis uveal effusion syndrome could
      be made.

PMID- 22134346
TI  - [Spectral transmission in blue filter intraocular lenses].
AB  - There is uncertainty in ophthalmology concerning the quality and spectral
      transmission of light of so-called blue filter intraocular lenses (IOL). Clinical
      users have noticed that such IOL's appear to have different color intensities.
      The discussion on medical changes by means of such IOL's is dependent on the real
      light transmission of these IOL's. To add some objective data we compared these
      IOL's by systematic transmission measurements and observed technical differences
      of diffraction and geometry as well as transmission differences. The result gives
      objective indications that differences between blue filter IOL's from different
      manufacturers are important and are detailed in this paper.

PMID- 22134347
TI  - [Heterogeneity of costs and performance for penetrating eye injuries and suturing
      amniotic membranes under DRG conditions :  Analysis of case constellations of the
      G-DRG C01B of the Regensburg University eye clinic].
AB  - BACKGROUND: Patients with penetrating eye injuries are a very heterogeneous group
      both medically and economically. Since 2009, treatment involving sutures for open
      eye injuries and cases requiring amniotic membrane transplantation (AMT) were
      allocated to DRG C01B of the German diagnosis-related group system. However,
      given the significant clinical differences between these treatments, an
      inhomogeneity of costs to performance is postulated. This analysis describes case
      allocation problems within the G-DRG C01B category and presents solutions.
      METHODS: A retrospective analysis was conducted from the standardized G-DRG data
      of 277 patients with open eye injuries and AMT between 2007 and 2008, grouped
      under the 2008 G-DRG system version to the G-DRG C01Z category. This data was
      provided by the Department of Ophthalmology at the University Hospital
      Regensburg. Additionally case-based data of the following were supplemented:
      length of surgery, time of anesthesia and intensity of patient care. Fixed and
      variable costs were determined for surgery and other inpatient treatment.
      Finally, an analysis of the heterogeneity of costs within the G-DRG C01B of the G
      DRG system 2009 was implemented. RESULTS: Inhomogeneity was evident within the G
      DRG C01B of the G-DRG system 2009 for the two groups suture of open eye injuries
      and AMT concerning the parameters length of stay, proportion of high outliers and
      cost per case. Multiple surgeries during an inpatient stay lead to an extended
      length of stay and increasing costs, especially within the AMT group. Intensity
      of patient care and the consideration of patient comorbidity did not yield
      relevant differences. CONCLUSION: The quality of the G-DRG system is measured by
      its ability to obtain adequate funding for highly complex and heterogeneous
      cases. Specific modifications of the G-DRG structures could increase the
      appropriateness of case allocation for patients with open eye injuries within the
      G-DRG C01B of the German DRG system 2009. As a result of the present study, cases
      with amniotic membrane transplantation should not be allocated to the G-DRG C01B.
      A petition has been presented by the German Association of Ophthalmology (DOG) to
      the German DRG Institute to restructure the G-DRG C01B. Data-based analysis is an
      essential prerequisite for a constructive development of the G-DRG system and a
      necessary tool for the active participation of medical societies in this process.

PMID- 22134348
TI  - Successful alternative treatment of extensively drug-resistant tuberculosis in
      Argentina with a combination of linezolid, moxifloxacin and thioridazine.
AB  - OBJECTIVES: Current drug choices to treat extensively drug-resistant (XDR)
      tuberculosis (TB) are scarce; therefore, information on the safety, tolerability
      and efficacy of alternative regimens is of utmost importance. The aim of this
      study was to describe the management, drug adverse effects and outcome of
      alternative combined treatment in a series of XDR-TB patients. PATIENTS AND
      METHODS: A retrospective study was performed on 17 non-AIDS, pulmonary adult
      patients with XDR-TB admitted to a referral treatment centre for infectious
      diseases in Buenos Aires from 2002 through 2008. Drug susceptibility testing was
      performed under regular proficiency testing and confirmed at the national TB
      reference laboratory. RESULTS: Linezolid was included in the drug regimens of all
      patients; moxifloxacin and/or thioridazine were included in the regimens of 14
      patients. Clinically tractable drug adverse effects were observed in nine
      patients, the most frequent being haematological disorders and neurotoxicity. In
      two patients, thioridazine was discontinued. Negative culture conversion was
      achieved in 15 patients, 11 completed treatment meeting cure criteria, 4 are
      still on follow-up with good evolution, 1 defaulted treatment and 1 was lost to
      follow-up. CONCLUSIONS: The combination of linezolid, moxifloxacin and
      thioridazine is recommended for compassionate use in specialized centres with
      expertise in the management of XDR-TB.

PMID- 22134350
TI  - The influence of gemcitabine pathway polymorphisms on treatment outcome in
      patients with malignant mesothelioma.
AB  - OBJECTIVE: Identification of biomarkers that could predict gemcitabine efficacy
      and toxicity is a key issue in the development of individualized therapy. The aim
      of our study was to evaluate the influence of gemcitabine pathway polymorphisms
      on treatment outcome in patients with malignant mesothelioma (MM). METHODS: In
      total, 107 patients with MM, treated with gemcitabine-platinum chemotherapy, were
      genotyped for 11 polymorphisms in deoxycytidine kinase, ribonucleotide reductase
      M1 (RRM1), and cytidine deaminase genes using KASPar assays. Binary logistic
      regression was used to evaluate the influence of selected polymorphisms on tumor
      response and occurrence of treatment-related toxicity, while their influence on
      survival was estimated by Cox proportional hazards model. A haplotype analysis
      was carried out to assess the combined effect of RRM1 polymorphisms. RESULTS:
      Deoxycytidine kinase and cytidine deaminase polymorphisms did not influence
      treatment outcome in patients with MM. In multivariable analysis, RRM1 2927A>C
      polymorphism significantly decreased overall survival probability [hazard ratio
      (HR)=2.02; 95% confidence interval (CI)=1.11-3.65; P=0.021]. Two promoter
      polymorphisms, RRM1 -524T>C and -37C>A, decreased the odds of nausea/vomiting
      grade>=2 occurrence [odds ratio (OR)=0.25; 95% CI=0.10-0.60; P=0.002 and OR=0.26;
      95% CI=0.11-0.63; P=0.003, respectively]. RRM1 TTCCA haplotype was associated
      with worse tumor response (OR=16.67; 95% CI=2.38-100.00; P=0.004) and worse
      overall survival (HR=2.97; 95% CI=1.46-6.06; P=0.003) compared with the most
      frequent TTCAA haplotype, while TCACA haplotype influenced nausea/vomiting
      grade>=2 occurrence (OR=0.27; 95% CI=0.12-0.60; P=0.001). CONCLUSION: RRM1
      polymorphisms as well as haplotypes showed an association with gemcitabine
      treatment efficacy and toxicity; therefore, they should be validated as potential
      markers for the prediction of clinical outcome in patients with MM.

PMID- 22134351
TI  - Confirming and establishing patency of glaucoma drainage devices using trypan
      blue.
AB  - The use of trypan blue is increasing in complicated cataract, retina, and
      glaucoma surgeries. We report on the use of trypan blue to help visualize the
      capsule over a glaucoma drainage implant and to assess adequate flow in different
      situations involving both valved and nonvalved implants. These cases demonstrate
      3 key points. One, when completing the second stage of a tube, it is essential to
      prime the tube to ensure adequate flow. Two, when extensive conjunctival scarring
      is present, trypan blue can be used to stain the capsule around the plate and
      confirm adequate flow. Three, if one is concerned of the functionality of a
      valved glaucoma implant, trypan blue can be used to both confirm and reestablish
      functionality of the valve mechanism.

PMID- 22134352
TI  - The prevalence of primary glaucoma in mainland China: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To estimate the prevalence of primary glaucoma in mainland China and
      to quantify its association with age, sex, and region. METHODS: Population-based
      studies that reported the prevalence of primary open-angle glaucoma (POAG) or/and
      primary angle-closure glaucoma (PACG) among adult populations in mainland China
      were identified through systematic searches. Fourteen articles providing 12
      population-based studies were included. The overall pooled prevalence estimates
      were calculated using a random-effects model. A logistic metaregression was used
      to model the associations between the odds ratio (OR) and 95% confidence interval
      of primary glaucoma and age, sex, and region. RESULTS: The overall pooled
      prevalence of POAG was 0.7% (95% confidence interval, 0.4-1.2), and PACG was
      found in 1.4% (1.0%, 1.7%). The OR per decade increase in age was 1.68 (1.12,
      2.52) for POAG, and 2.11 (1.72, 2.60) for PACG. The OR of POAG prevalence was
      0.65 (0.26, 1.62) between men and women. Chinese women were 1.75 (1.20, 2.56)
      times more likely than men to have PACG. The OR between western China and east
      China were 0.37 (0.10, 1.35) for POAG, and 1.06 (0.63, 1.76) for PACG. The OR
      between urban China and rural China were 3.92 (1.55, 9.92) for POAG, and 1.07
      (0.55, 2.10) for PACG. CONCLUSIONS: The prevalence of PACG was approximately
      double that of POAG in adult Chinese. The rate of change of PACG prevalence with
      age increased more rapidly than that of POAG. The prevalence of POAG in urban was
      higher than that in rural. PACG was more common in women than in men.

PMID- 22134353
TI  - Technique for intraoperative reuse of Ex-PRESS delivery system.
AB  - PURPOSE: To report a new technique for reloading the Ex-PRESS glaucoma filtration
      device on the Ex-PRESS delivery system (Alcon Laboratories) for revised placement
      of an implant. PATIENT AND METHODS: The Ex-PRESS is provided on a single-use
      delivery system. A patient who underwent Ex-PRESS placement was noted
      intraoperatively to have had an unsatisfactory implant position upon initial
      insertion. The used inserter metallic rod was manipulated to resume its original
      shape. The implant was removed and reloaded onto the delivery system, which was
      then used to place it in the desired position. RESULTS: Intraoperative delivery
      system reloading is possible and facilitates repositioning of the Ex-PRESS
      implant. CONCLUSIONS: This technique for reloading the Ex-PRESS will allow the
      surgeon to make adjustments to an unsatisfactorily positioned implant upon
      initial insertion. This may help optimize implant positioning, minimize insertion
      malpositioning, and reduce the cost and time of using more than 1 device.

PMID- 22134354
TI  - miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial
      mesenchymal transitions.
AB  - Recently, the inhibition of epithelial-mesenchymal-transition (EMT) by p53 has
      been described as a new mode of tumor suppression which presumably prevents
      metastasis. Here we report that activation of p53 down-regulates the EMT-inducing
      transcription factor SNAIL via induction of the miR-34a/b/c genes. Suppression of
      miR-34a/b/c caused up-regulation of SNAIL and cells displayed EMT markers and
      related features, as enhanced migration and invasion.  Ectopic miR-34a induced
      mesenchymal-epithelial-transition (MET) and down-regulation of SNAIL, which was
      mediated by a conserved miR-34a/b/c seed-matching sequence in the SNAIL 3'-UTR.
      miR-34a also down-regulated SLUG and ZEB1, as well as the stemness factors BMI1,
      CD44, CD133, OLFM4 and c-MYC. Conversely, the transcription factors SNAIL and
      ZEB1 bound to E-boxes in the miR-34a/b/c promoters, thereby repressing miR-34a
      and miR-34b/c expression. Since ectopic miR-34a prevented TGF-beta-induced EMT,
      the repression of miR-34 genes by SNAIL and related factors is part of the EMT
      program. In conclusion, the frequent inactivation of p53 and/or miR-34a/b/c found
      in cancer may shift the equilibrium of these reciprocal regulations towards the
      mesenchymal state and thereby lock cells in a metastatic state.

PMID- 22134355
TI  - Hemodynamic analysis of intracranial aneurysms with daughter blebs.
AB  - BACKGROUND AND PURPOSE: Intracranial aneurysms with daughter blebs appear to have
      a higher risk of rupture. Whether hemodynamic factors are involved in this
      phenomenon is not clear. METHODS: 54 patient-specific aneurysms harboring 69
      daughter blebs were divided into ruptured and unruptured groups based on their
      clinical history. Realistic models were retrospectively constructed and analyzed
      by a computational fluid dynamic method. RESULTS: There were no differences in
      the aspect ratio and morphology type of the aneurysms, the size of blebs or other
      common risk factors between the two groups. The wall shear stress (WSS) was
      significantly lower while the oscillatory shear index (OSI) was higher in the
      daughter blebs than in the primary aneurysms. Bleb-bearing aneurysms with a
      rupture history displayed significantly lower WSS in the daughter bleb. Of the
      daughter blebs, 73.9% were localized to the impingement region of the inflow jet.
      CONCLUSION: These observations indicate that low WSS and high OSI in the daughter
      blebs might be involved in increasing the risk of rupture. The localized striking
      force caused by inflow jets may contribute to the development of daughter blebs.
      However, a precise role of hemodynamics in predicting the future rupture of
      daughter blebs needs further study.

PMID- 22134356
TI  - Profiling of gender-specific rat plasma proteins associated with susceptibility
      or resistance to diet-induced obesity.
AB  - Obesity-prone (OP) and obesity-resistant (OR) rats with different responses to
      development of obesity in spite of the same genetic background are useful animal
      models for searching for markers during the development of obesity. Here, we
      investigated whether plasma proteins of OP and OR rats may behave in a different
      way in males and females. We performed a comparative proteomic analysis using 2
      DE combined with MALDI-TOF/MS on proteins from OP and OR male and female rats to
      discover gender-specific rat plasma proteins associated with susceptibility or
      resistance to diet-induced obesity. A total of 29 proteins showing differential
      expression between the groups were identified by MALDI-TOF/MS and database
      searches. These proteins were classified into 4 groups according to their
      regulation patterns in response to diet and gender. 22 proteins showed
      significant differences between OP and OR rats in males and/or females (Group I,
      II, and III) and 7 proteins exhibited only a high fat diet (HFD)-responsive
      difference in male or female rats (Group IV). In conclusion, the proteins
      negatively (ITIH3, FGG, TUBB5, and ZAG) or positively (Hp, ITIH4, and RBP)
      correlated with obesity found in this study could be used for selection of new
      targets for gender specific-medical treatment of obesity.

PMID- 22134357
TI  - Proteomic analysis of papaya fruit ripening using 2DE-DIGE.
AB  - Papayas have a very short green life as a result of their rapid pulp softening as
      well as their susceptibility to physical injury and mold growth. The ripening
      related changes take place very quickly, and there is a continued interest in the
      reduction of postharvest losses. Proteins have a central role in biological
      processes, and differential proteomics enables the discrimination of proteins
      affected during papaya ripening. A comparative analysis of the proteomes of
      climacteric and pre-climacteric papayas was performed using 2DE-DIGE. Third seven
      proteins corresponding to spots with significant differences in abundance during
      ripening were submitted to MS analysis, and 27 proteins were identified and
      classified into six main categories related to the metabolic changes occurring
      during ripening. Proteins from the cell wall (alpha-galactosidase and invertase),
      ethylene biosynthesis (methionine synthase), climacteric respiratory burst,
      stress response, synthesis of carotenoid precursors (hydroxymethylbutenyl 4
      diphosphate synthase, GcpE), and chromoplast differentiation (fibrillin) were
      identified. There was some correspondence between the identified proteins and the
      data from previous transcript profiling of papaya fruit, but new, accumulated
      proteins were identified, which reinforces the importance of differential
      proteomics as a tool to investigate ripening and provides potentially useful
      information for maintaining fruit quality and minimizing postharvest losses.

PMID- 22134358
TI  - Potential drug targets on insomnia and intervention effects of Jujuboside A
      through metabolic pathway analysis as revealed by UPLC/ESI-SYNAPT-HDMS coupled
      with pattern recognition approach.
AB  - Potential metabolites from the metabolic pathways could be therapeutic targets
      and useful for the discovery of broad spectrum drugs. UPLC/ESI-SYNAPT-HDMS
      coupled with pattern recognition methods including PCA, PLS-DA, OPLS-DA and
      Heatmap were integrated to examine the global metabolic signature of insomnia and
      intervention effects of Jujuboside A (JuA). Six unique pathways of the insomnia
      were identified using Ingenuity Pathway Analysis (IPA) software. The VIP-value
      threshold cutoff of the metabolites was set to 10, above this threshold, were
      filtered out as potential target biomarkers. Sixteen distinct metabolites were
      identified from these pathways, and 6 of them can be considered for rational drug
      design. It was further experimental validation that the changes in metabolic
      profiling were restored to their baseline values after JuA treatment according to
      the multivariate data analysis. Potential metabolite network of the insomnia was
      preliminarily predicted JuA-target interaction networks, and could be further
      explored for in silico docking studies with suitable drugs. Thus, our method is
      an efficient procedure for drug target identification through metabolic analysis.
      It can guide testable predictions, provide insights into drug action mechanisms
      and enable us to increase research productivity toward metabolomic drug
      discovery.

PMID- 22134359
TI  - Report of the 20th European Stroke Conference, Hamburg, May 24-27, 2011.

PMID- 22134360
TI  - IL-6-induced epithelial-mesenchymal transition promotes the generation of breast
      cancer stem-like cells analogous to mammosphere cultures.
AB  - Recently, the inflammatory cytokine IL-6 has been reported as a potent inducer of
      epithelial-mesenchymal transition (EMT) in breast cancer cells with an epithelial
      phenotype. Furthermore, EMT induces stem cell features in normal and transformed
      mammary cells. We explored whether IL-6-induced EMT promoted the generation of
      breast cancer stem-like cells (BrCSCs) in epithelial-like breast cancer cells,
      and whether the cytokines EGF and bFGF, analogous to IL-6, per se induced
      epithelial-mesenchymal transition, resulting in the enrichment of BrCSCs in
      mammosphere cultures. Herein, we provide evidence that IL-6 is capable of
      generating CD44+ cells with stem-like properties through induction of the EMT in
      the epithelial-like T47D breast cancer cells. We also show that mammosphere
      cultures of epithelial-like breast cancer cells, T47D, MCF7, ZR-75-1 and MDA-MB
      453 cells, consistently generated stem-like cancer cells solely as a result of
      the EGF and bFGF cytokines in the mammosphere media mediating EMT. This finding
      demonstrated the link between the inflammatory cytokine IL-6 and BrCSCs and
      identified an important mechanism for the enrichment of BrCSCs in mammosphere
      cultures. Thus, EMT appears to be a critical mechanism for the induction of
      cancer cells with stem-like properties, and EMT of non-stem cancer cells could be
      a source of CSCs.

PMID- 22134361
TI  - Structural organization and dimensionality at the hands of weak intermolecular
      Au...Au, Au...X and X...X (X = Cl, Br, I) interactions.
AB  - The salts K[AuCl(2)(CN)(2)].H(2)O (1), K[AuBr(2)(CN)(2)].2H(2)O (2) and
      K[AuI(2)(CN)(2)].1/3H(2)O (3) were synthesized and structurally characterized.
      Compound 1 crystallizes as a network of square planar [AuCl(2)(CN)(2)](-) anions
      separated by K(+) cations. However, 2 and 3 feature 2-D sheets built by the
      aggregation of [AuX(2)(CN)(2)](-) anions via weak, intermolecular X...X
      interactions. The mixed anion double salts
      K(3)[Au(CN)(2)](2)[AuBr(2)(CN)(2)].H(2)O (4) and
      K(5)[Au(CN)(2)](4)[AuI(2)(CN)(2)].2H(2)O (5) were also synthesized by
      cocrystallization of K[Au(CN)(2)] and the respective K[AuX(2)(CN)(2)] salts.
      Similarly to 2 and 3, the [Au(CN)(2)](-) and [AuX(2)(CN)(2)](-) anions form 2-D
      sheets via weak, intermolecular Au(I)...X and Au(I)...Au(I) interactions. In the
      case of 5, a rare unsupported Au(I)...Au(III) interaction of 3.5796(5) A is also
      seen between the two anionic units. Despite the presence of Au(I) aurophilic
      interactions of 3.24-3.45 A, neither 4 nor 5 exhibit any detectable emission at
      room temperature, suggesting that the presence of Au(I)...X or Au(I)...Au(III)
      interactions may affect the emissive properties.

PMID- 22134362
TI  - Pseudophakic cystoid macular edema.
AB  - PURPOSE OF REVIEW: Pseudophakic cystoid macular edema (PCME) is a common cause of
      visual impairment after cataract surgery. This article systematically reviews and
      discusses the epidemiology, risk factors, diagnosis, and treatment of PCME, with
      a focus on advances in the past 1-2 years. RECENT FINDINGS: The incidence of PCME
      has declined with the advent of modern surgical techniques. Optical coherence
      tomography (OCT) has become an important adjunct to biomicroscopy and fluorescein
      angiography. PCME prophylaxis with topical nonsteroidal anti-inflammatory drugs
      remains unproven because long-term visual outcomes and comparative effectiveness
      studies are lacking. Chronic, refractory CME remains a therapeutic challenge, but
      investigational therapies with potential include corticosteroid intravitreal
      injections and implants, and intravitreal anti-vascular endothelial growth factor
      treatments. Few studies have assessed surgical options. SUMMARY: There is
      currently a lack of well designed randomized clinical trials to guide the
      treatment of PCME.

PMID- 22134363
TI  - Ever-evolving technological advances in cataract surgery:  can perfection be
      achieved?

PMID- 22134364
TI  - The changing fate of the corneal endothelium in cataract surgery.
AB  - PURPOSE OF REVIEW: Corneal endothelial cell loss remains a well known,
      undesirable side-effect of cataract surgery that may, in severe cases, negatively
      impact patients' postoperative visual outcomes. This article reviews the current
      literature and describes in detail how the degree of corneal endothelial cell
      loss is influenced by specific patient risk factors, as well as the arrival of
      newer surgical techniques and technologies. RECENT FINDINGS: Recent studies have
      demonstrated a reduction in corneal endothelial cell loss after
      phacoemulsification with the use of viscoelastic materials and modifications in
      phacoemulsification technology. Some patient characteristics may predispose
      patients to increased endothelial cell loss during cataract surgery. SUMMARY:
      Advances in surgical technique, the implementation of newer surgical technologies
      such as torsional ultrasound and viscoelastic devices, and aspects of patients'
      preexisting medical history may lead to varying degrees of endothelial cell loss
      after cataract surgery. Appropriately addressing these issues during the
      perioperative period may improve the rate of endothelial cell loss, and thus
      further enhance the visual outcome of patients undergoing cataract surgery.

PMID- 22134366
TI  - Synthesis of N-(2-chloro purin-6-yl) aza-18-crown-6 and its interaction with
      human serum albumin.
AB  - The synthesis of novel purine nucleosides-linked azacrown ethers in the C6
      position, N-(2-chloro purin-6-yl) aza-18-crown-6 (NCPAC), was described. This new
      nucleoside analogue can be prepared from a series of N9-modified nucleosides and
      the method allows for new and easy modification of the nucleosides. The
      interaction between NCPAC and human serum albumin (HSA) was studied using
      molecular docking and fluorescence techniques. Thermodynamics revealed that the
      interaction was entropy driven with predominantly hydrophobic forces. From the
      observed Foster's-type fluorescence resonance energy transfer, the donor (Trp 214
      in HSA) to acceptor (NCPAC) distance was calculated to be 3.6 nm. The
      conformational changes of HSA due to the interaction were investigated
      qualitatively from synchronous fluorescence spectra. Molecular docking studies
      were performed to obtain information on the possible residues involved in the
      interaction process.

PMID- 22134367
TI  - Influence of metabolic syndrome on development of cardiac allograft vasculopathy
      in the transplanted heart.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is the main cause of graft
      failure and death 1 year after heart transplantation (HTx). Metabolic syndrome
      (MS) increases the risk of cardiovascular events by endothelial dysfunction. The
      purpose of this study was to determine if patients with MS developed a higher
      risk of CAV 1 year after HTx. METHODS: Since January 2004 until April 2009, 155
      HTx patients were recruited. Cardiopulmonary transplants were excluded (12
      patients), as well as retransplants (5 patients), pediatric transplants (11
      patients), patients who refused to participate (3 patients), and those who died
      during the first year (35 patients). The final analysis included 89 patients. MS
      was diagnosed when Adult Treatment Panel III modified and revised criteria were
      met, before HTx or after the first 3 months. CAV was diagnosed through
      intravascular ultrasound performed 1 month and 1 year after HTx. CAV was defined
      as an intimal thickening >= 0.5 mm in the follow-up with regard to the one of the
      basal study. RESULTS: Development of CAV was significantly higher in patients
      with MS (59% vs. 19%, P<0.0001). Patients with more criteria of MS had a higher
      development of CAV: no criteria (4%); one criterion (4%); two criteria (47%);
      three criteria (62%); four criteria (75%); and five criteria (100%). Variables
      related to CAV in a multivariate analysis were MS (odds ratio [OR] 7.97; 95%
      confidence interval [CI]: 2.77-22.96; P<0.001), donor's age (OR 1.07; 95% CI:
      1.01-1.13; P=0.019), low high-density lipoprotein cholesterol (OR 0.26; 95% CI:
      0.09-0.71; P=0.009), and hypertriglyceridemia (OR 4.08; 95% CI: 1.45-11.50;
      P=0.008). CONCLUSIONS: Presence of MS distinguishes a subgroup of patients with
      high risk of developing CAV. Narrow and personalized monitoring of these patients
      would be recommendable.

PMID- 22134368
TI  - Kinetics of T-lymphocyte subsets and posttransplant opportunistic infections in
      heart and kidney transplant recipients.
AB  - BACKGROUND: The potential use of T-lymphocyte measurements as infection risk
      markers after solid organ transplant has not been fully investigated. We analyzed
      the kinetics of T-lymphocyte subsets within the first 8 months posttransplant and
      their correlation with opportunistic infections (OIs) in solid organ transplant
      recipients. METHODS: Serial measurement of CD4 and CD8 T cells was performed
      retrospectively in 48 heart transplant recipients (HTR) and 42 kidney transplant
      recipients (KTR). Generalized estimating equation models were used to analyze
      longitudinal data separately for HTR and KTR. RESULTS: An initial CD4 T-cell drop
      (at months 1 and 2, in HTR and KTR, respectively) coincided with the peak of OIs.
      HTR with a low nadir CD4 T-cell count (<= 200/MUL) showed poor CD4 T-cell
      recovery (175 +/- 277 cells/MUL at baseline vs 242 +/- 99 cells/MUL at month 8)
      and their CD8 T cells increased from 153 +/- 194 cells/MUL at baseline to 601 +/-
      399 cells/MUL at month 8. KTR with a low nadir CD4 T-cell count (<= 200/MUL)
      showed a modest CD4 T-cell recovery (138 +/- 46 cells/MUL at baseline vs. 440 +/-
      448 cells/MUL at month 8), and their CD8 T cells increased from 90 +/- 41
      cells/MUL at baseline to 450 +/- 242 cells/MUL at month 8. HTR developing OIs had
      lower CD4 (P<0.001) and CD8 T cells (P=0.001) than those without infections,
      whereas in KTR the risk for OIs seemed restricted to patients with low CD8 T
      cells. HTR with OIs had a low CD4/CD8 T-cell ratio, whereas KTR had a high
      CD4/CD8 T-cell ratio. CONCLUSIONS: Determination of T-lymphocyte subsets is a
      simple and effective parameter to identify patients at risk of developing OIs.

PMID- 22134369
TI  - Enteroscopic biopsies in the management of pancreas transplants:  a proof of
      concept study for a novel monitoring tool.
AB  - BACKGROUND: Although percutaneous biopsies are considered to be the gold standard
      in diagnosing pancreas graft rejection, they are not performed routinely because
      of their association with severe complications. On the other hand, correct
      diagnosis of rejection is essential but may be difficult in cases of enteric
      drainage, particularly in patients with a pancreas transplant alone or a pancreas
      after kidney transplant. METHODS: Pancreas recipients who underwent enteroscopy
      between May 2005 and September 2009 were included in this retrospective analysis.
      Biopsies were graded 0 to 4 for interstitial and vascular changes. RESULTS:
      During the study period a total of 65 simultaneous pancreas-kidney transplants,
      13 pancreas after kidney transplants and 4 pancreas transplants alone were
      performed. Sixty-three patients underwent a single enteroscopy, 10 had two, and 6
      had three or more. Indications were protocol graft monitoring (n=73), graft
      dysfunction (n=17), enteric hemorrhage (n=9), or other (n=3). The duodenal
      segment was accessed in 76 instances (75%) with abnormal findings in 23. A total
      of 69 biopsies were obtained and revealed normal mucosa in 49 cases (71%).
      Histology showed signs of acute rejection in 11 cases. The upper gastrointestinal
      tract was also assessed, and, in 13 cases, additional pathologies were identified
      including gastroduodenitis (n=10), gastric/duodenal ulcer (n=2), and hemorrhagic
      esophagitis (n=1). No procedure-related complication occurred. CONCLUSIONS: This
      series of enteroscopies demonstrates that the duodenal segment of a pancreatic
      graft is accessible using our implant technique, and thus permitting biopsies to
      be obtained and endoscopic interventions to be performed.

PMID- 22134370
TI  - Vitamin D deficiency in lung transplant patients: is it important?
AB  - BACKGROUND: Vitamin D deficiency has been reported in different chronic pulmonary
      diseases like asthma and chronic obstructive pulmonary disease, but little is
      known in lung transplant recipients. METHODS: Serum 25-hydroxyvitamin D (25-OHD)
      levels and pulmonary function (forced expiratory volume in 1 sec [FEV(1)]
      %predicted) were measured in 131 lung transplant patients during their yearly
      posttransplant check-up hospital stay, and the total number of infections and
      perivascular/peribronchiolar rejections were assessed from transplantation on.
      RESULTS: Vitamin D deficiency (<30 ng/mL) occurred in 62 of 131 patients (47.3%),
      of whom 26 (19.8%) were severely deficient (<20 ng/mL). The FEV(1) was
      significantly lower in the deficient group compared with the group with normal
      levels (P=0.019). Moreover, we could find an association between FEV(1) and 25
      OHD levels in univariate analysis (P=0.018), which remained significant in
      multivariate analysis (P=0.012). The same holds true for the association between
      25-OHD levels and the peak postoperative FEV(1) (P=0.021 in multivariate
      analysis). We also identified significantly more patients with moderate to severe
      B-grade rejections in the deficient group (P=0.0038). CONCLUSION: Vitamin D
      deficiency is present in 47% of our lung transplant patients and seems
      independently associated with a lower FEV(1) and more severe B-grade rejections.
      This study raises the potential need for additional vitamin D treatment in lung
      transplantation and clearly indicates the role of a randomized placebo-controlled
      trial with vitamin D supplementation, which is ongoing in our center.

PMID- 22134371
TI  - Soy lecithin interferes with mitochondrial function in frozen-thawed ram
      spermatozoa.
AB  - Egg yolk and milk are the 2 major membrane cryoprotectants commonly used in 
      freezing media for the long-term preservation of semen (alone or in  combination
      with others). However, in recent years, there have been increasing  arguments
      against the use of egg yolk or milk because of the risk of  introducing diseases
      through the use of cryopreserved semen. In this study, we  analyzed the
      protective effect of lecithin as an alternative to egg yolk for  the
      cryopreservation of ram semen, using a range of functional markers for  sperm
      viability, motility, apoptosis, and mitochondrial functionality analyses 
      (mitochondrial inner membrane surface [MIMS], mitochondrial inner membrane 
      potential [MIMP], and cell membrane potential) as methods of assessment in 
      samples diluted in 3 different media: Tris-citrate-glucose as control and 2 
      media supplemented with soy lecithin or egg yolk. The results showed that 
      lecithin was able to effectively protect certain sperm quality characteristics 
      against freezing-induced damage. However, lecithin induced loss of  mitochondrial
      membrane potential or mitochondrial loss that was not reflected  by modifications
      in sperm motility in fresh semen. MIMS and MIMP values  decreased in thawed
      lecithin-treated samples, concomitant with a lower  (P < .05) percentage of total
      and progressively motile cells,  compared with those in egg yolk-containing
      samples. Further incubation  of thawed samples revealed changes in motility and
      mitochondrial functionality  that otherwise would not have been detected. These
      results indicated that  lecithin may have affected the inner mitochondrial
      membrane in frozenthawed  spermatozoa and confirmed that sublethal damages that
      seriously affect sperm  functionality, not detected by classic sperm quality
      analyses, can be  evidenced by changes in the inner mitochondrial membrane
      surface. These  findings strengthen the relationship between mitochondrial
      membrane potential  and motility and show that the mitochondrial alterations
      induced by the  cryopreservation process could be specific targets for the
      improvement of  semen cryopreservation protocols.

PMID- 22134373
TI  - Adenosine A2A-receptor antagonism and pathophysiology of Parkinson's disease and
      drug-induced movement disorders.
AB  - Parkinson's disease and drug-induced movement disorders (DIMDs) have
      commonalities in etiology based on impaired dopamine-based neurotransmission.
      Adenosine A(2A)-receptor antagonism may provide a new mechanism through which
      these disorders can be managed. In the motor circuit, tonic output from the
      globus pallidus and substantia nigra regulates movement via opposing excitatory
      and inhibitory inputs to the cerebral cortex through the direct and indirect
      pathways. Increased activity of the direct pathway increases movement via an
      inhibitory effect on thalamocortical projection neurons; increased activity of
      the indirect pathway has the opposite effect. Regulation of these pathways is
      mediated primarily by reciprocal inhibitory interactions between dopamine and
      adenosine receptors on neurons of these pathways. Adenosine A(2A) receptors are
      colocalized with dopamine D(2) receptors on the indirect pathway neurons, with
      A(2A) activation opposing the effect of D(2) activation. The A(2A) receptors'
      role in the pathophysiology of Parkinson's disease and DIMDs is evidenced by the
      upregulation of A(2A) receptors in patients with Parkinson's disease and patients
      receiving long-term administration of dopamine blockers. Further, A(2A)-receptor
      antagonists are effective in reversing parkinsonian motor deficits and
      extrapyramidal symptoms in animal models of Parkinson's disease and DIMDs.
      Understanding the role of A(2A)-receptor antagonism in the pathophysiology of
      Parkinson's disease and DIMD has therapeutic implications.

PMID- 22134372
TI  - Planar cell polarity signaling in craniofacial development.
AB  - Out of the several signaling pathways controlling craniofacial development, the
      role of planar cell polarity (PCP) signaling is relatively poorly understood.
      This pathway, originally identified as a mechanism to maintain cell polarity
      within the epithelial cells of the Drosophila wing, has been linked to the proper
      development of a wide variety of tissues in vertebrates and invertebrates. While
      many of the pathway members are conserved, it appears that some of the members of
      the pathway act in a tissue-specific manner. Here, we discuss the role of this
      pathway in vertebrate craniofacial development, highlighting cranial neural crest
      migration, skull and palate formation and the role of non-traditional modulators
      of PCP signaling within this developmental process.

PMID- 22134374
TI  - Genetic variation in CD83 and risks of cervical and vulvar cancers: a population
      based case-control study.
AB  - OBJECTIVES: The CD83 glycoprotein is a marker of dendritic cell maturation that
      may contribute to the T cell response to oncogenic human papillomavirus (HPV)
      infection. Whether single nucleotide polymorphisms (SNPs) in CD83 influence the
      risk of HPV-related genital cancers has not been adequately studied. We
      investigated whether the common genetic variation of the CD83 region was
      associated with the risks of cervical and vulvar cancers in a population-based
      case-control study conducted in the Seattle-Puget Sound Region. METHODS: A total
      of 17 tagSNPs were genotyped in the CD83 region of 886 cervical cases, 517 vulvar
      cases and 1100 controls. Odds ratio (OR) and 95% confidence intervals (CI) were
      computed to assess the risk of cervical and vulvar cancers. The interaction
      between the tagSNPs and cigarette smoking was also explored. RESULTS: TagSNPs in
      the CD83 chromosomal region were not associated with risk of either cervical or
      vulvar cancer. TagSNP rs853360 was associated with a decreased risk of cervical
      squamous cell carcinoma (SCC) (OR=0.80; 95% CI: 0.66-0.98). CONCLUSIONS: Our
      results do not suggest that the common genetic variation of CD83 is related to
      cervical or vulvar cancers. The association between tagSNP rs853360 and risk of
      cervical SCC is likely to be due to chance. If larger or pooled studies confirm
      our results, CD83 has little or no influence in the risk of HPV-related cancers.

PMID- 22134375
TI  - A systematic review of sexual concerns reported by gynecological cancer
      survivors.
AB  - OBJECTIVE: To identify physical, psychological and social sexual concerns
      reported by gynecological (GYN) cancer survivors. METHODS: A systematic review of
      the literature was conducted using CINAHL, PubMed and PsycInfo databases.
      Reference lists from articles provided additional relevant literature. Only
      research articles from peer-reviewed journals were included. A total of 37
      articles were located; 34 explored women's sexual concerns following
      gynecological cancer diagnosis and treatment and 3 tested interventions for
      sexual concerns in women with gynecological cancer. RESULTS: Sexual concerns were
      identified across all dimensions of sexuality. Common concerns in the physical
      dimension were dyspareunia, changes in the vagina, and decreased sexual activity.
      In the psychological dimension, common concerns were decreased libido,
      alterations in body image, and anxiety related to sexual performance. And in the
      social dimension, common concerns were difficulty maintaining previous sexual
      roles, emotional distancing from the partner, and perceived change in the
      partner's level of sexual interest. Of the three psychoeducational intervention
      studies, two reported improvements in physical aspects of sexual function, and
      one reported improved knowledge, but without resolution of sexual concerns.
      CONCLUSION: Gynecological cancer survivors experience a broad range of sexual
      concerns after diagnosis and treatment, but the majority of studies emphasized
      physical aspects of sexuality, and may not adequately represent women's
      psychological and social sexual concerns. Health care providers should remain
      mindful of psychological and social sexual concerns when caring for gynecologic
      cancer survivors. Future research should systematically evaluate the full range
      of sexual concerns in large, representative samples of GYN cancer survivors and
      develop and test interventions to address those concerns.

PMID- 22134376
TI  - [Clinical application of pain-related evoked potentials].
AB  - Pain-related evoked potentials (PREPs) represent a novel method for the
      evaluation of peripheral and central nociceptive pathways, e.g. in the diagnosis
      of small fiber neuropathy (SFN) or after therapeutic interventions for headache.
      Compared to contact heat-evoked and laser-evoked potentials, recording of PREPs
      is less stressful for the subjects and technically less demanding. The clinical
      usefulness of PREPs has been described for SFN associated with diabetes, HIV and
      hepatitis C infections as well as in headache and facial pain disorders. They
      have also been evaluated after interventional methods, such as direct current
      stimulation (tDCS). The article reviews and discusses the advantages and pitfalls
      of this technique in the context of recent clinical studies as compared to other
      paradigms of peripheral electrical stimulation and delineates perspectives and
      possible indications.

PMID- 22134378
TI  - Cyclodextrin-phosphane possessing a guest-tunable conformation for aqueous
      rhodium-catalyzed hydroformylation.
AB  - The inclusion of a guest inside the cavity of a new water-soluble cyclodextrin
      phosphane allows controlling the natural conformation of this ligand leading to
      an inversion of the regioselectivity during aqueous hydroformylation reaction.

PMID- 22134377
TI  - Realgar-induced apoptosis and differentiation in all-trans retinoic acid (ATRA)
      sensitive NB4 and ATRA-resistant MR2 cells.
AB  - Realgar has been used in Western medicine and Chinese traditional medicine since
      ancient times, and its promising anticancer activity has attracted much attention
      in recent years, especially for acute promyelocytic leukemia (APL). However, the
      therapeutic action of realgar treatment for APL remains to be fully elucidated.
      Cellular cytotoxicity, proliferation, apoptosis and differentiation were
      comprehensively investigated in realgar-treated cell lines derived from PML
      RARalpha+ APL patient, including the all-trans retinoic acid (ATRA)-sensitive NB4
      and ATRA-resistant MR2 cell lines. For analysis of key regulators of apoptosis
      and differentiation, gene expression profiles were performed in NB4 cells.
      Realgar was found to induce apoptosis and differentiation in both cell lines, and
      these effects were exerted simultaneously. Gene expression profiles indicated
      that genes influenced by realgar treatment were involved in the modulation of
      signal transduction, translation, transcription, metabolism and the immune
      response. Given its low toxicity, realgar is a promising alternative reagent for
      the therapy of APL. Our data contribute to an understanding of the underlying
      mechanism responsible for the therapeutic effects of realgar in the clinical
      treatment of APL.

PMID- 22134379
TI  - Neutral cuprous complexes as ratiometric oxygen gas sensors.
AB  - Four neutral mononuclear Cu(I) complexes, [Cu(pyin)(PPh(3))(2)] (1a),
      [Cu(pyin)(DPEphos)] (1b), [Cu(quin)(PPh(3))(2)] (2a) and [Cu(quin)(DPEphos)] (2b)
      (Hpyin = 2-(2-pyridyl)indole, Hquin = 2-(2-quinolyl)indole and DPEphos = bis(2
      (diphenylphosphino)phenyl)ether) have been synthesized. X-Ray crystal structure
      analysis revealed that the central Cu(I) ion in all complexes is in a distorted
      tetrahedral coordination environment. All four complexes display the typical
      metal-to-ligand charge transfer (MLCT) absorption band at 371, 363, 413 and 402
      nm, respectively. No emission was observed from any complexes in the solid state
      due to triplet-triplet annihilation. However, the complexes show unusual dual
      emission originating from intraligand charge-transfer (ILCT) and MLCT
      transitions, when dispersed in a rigid matrix (e.g. PMMA) or in frozen
      CH(2)Cl(2). The oxidation potential of Cu(I)/Cu(II) in these neutral complexes,
      ~0.5 V (vs. Ag/AgCl), is lower than those of cationic Cu(I) complexes. Films
      containing 10 wt% of these complexes in PMMA shows ratiometric fluorescent oxygen
      gas sensing property with a response ratio of 0.3-3.2 and response time of 3-4 s.
      Complex 2b acts as a ratiometric oxygen gas sensor with good reversibility
      through energy and electron transfer mechanisms under the loss of a counteranion.

PMID- 22134380
TI  - Dual-functional probes towards in vivo studies of brain connectivity and
      plasticity.
AB  - A Gd(3+) based paramagnetic dextran conjugate has been developed, which enables
      the tracking of neuroanatomical connectivity in the brain by both MR and optical
      imaging. Cell studies and subsequent in vivo experiments in rodents demonstrate
      efficient internalisation and transport properties of the new tracer molecule.

PMID- 22134382
TI  - N-heterocyclic carbene catalysed aerobic oxidation of aromatic aldehydes to aryl
      esters using boronic acids.
AB  - The organocatalytic behavior of N-heterocyclic carbenes in the aerobic oxidation
      of aromatic aldehydes to esters with boronic acids has been explored. This
      transition metal-free protocol allows access to a wide variety of aromatic esters
      in good to excellent yields under mild reaction conditions.

PMID- 22134381
TI  - Serotonin modulates worker responsiveness to trail pheromone in the ant Pheidole
      dentata.
AB  - As social insect workers mature, outside-nest tasks associated with foraging and
      defense are typically performed at higher frequencies. Foraging in ants is often
      a pheromonally mediated collective action performed by mature workers; age
      dependent differences in olfactory response thresholds may therefore proximately
      regulate task repertoire development. In the ant Pheidole dentata, foraging
      activity increases with chronological age in minor workers, and is chemically
      controlled. The onset of foraging in minor workers is accompanied by marked
      neuroanatomical and neurochemical changes, including synaptic remodeling in
      olfactory regions of the brain, proliferation of serotonergic neurons, and
      increased brain titers of monoamines, notably serotonin. We examined the linkage
      of serotonin and olfactory responsiveness by assaying trail-following performance
      in mature P. dentata minor workers with normal serotonin levels, or serotonin
      levels experimentally lowered by oral administration of the serotonin synthesis
      inhibitor alpha-methyltryptophan (AMTP). By assessing responsiveness to
      standardized pheromone trails, we demonstrate that trail-following behaviors are
      significantly reduced in serotonin-depleted workers. AMTP-treated individuals
      were less likely to initiate trail following, and oriented along pheromone trails
      for significantly shorter distances than untreated, similar-age workers. These
      results demonstrate for the first time that serotonin modulates olfactory
      processes and/or motor functions associated with cooperative foraging in ants.

PMID- 22134383
TI  - Control of CO2 adsorption heats by the Al distribution in FER zeolites.
AB  - Proper combination of template and optimized reaction conditions provides zeolite
      FER with homogeneous distribution of Al in the framework; this results in a new
      zeolite adsorbent exhibiting a constant heat of CO(2) adsorption.

PMID- 22134384
TI  - Plasma levels of matrix metalloproteinases and their inhibitors in hypertension: 
      a systematic review and meta-analysis.
AB  - BACKGROUND: Hypertension is a major cause of cardiovascular remodeling. In the
      cardiovascular system, the remodeling of the extracellular matrix is controlled
      by the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs
      (TIMPs). The aim of this meta-analysis is to elucidate the behavior of plasma MMP
      and TIMP levels in hypertension and their relationship to cardiovascular
      remodeling. METHODS: MEDLINE and EMBASE databases were searched up to July 2011.
      Studies were considered eligible if they provided values of plasma MMPs and TIMPs
      in hypertensive patients. Given the high variability of the plasma biomarker
      values among studies, the standardized mean difference (SMD) was calculated.
      RESULTS: Ten studies provided plasma MMP-9; the SMD between 778 hypertensive
      patients and 669 controls was 1.95 units (P < 0.05). Thirteen studies provided
      plasma TIMP-1; the SMD between 851 hypertensive patients and 646 normotensive
      individuals was 1.92 units (P < 0.01). Three studies investigated whether plasma
      TIMP-1 predicted left ventricular (LV) remodeling; the SMD between 92
      hypertensive patients with and 88 hypertensive patients without LV hypertrophy
      was 5.81 units (P < 0.05). As for diastolic heart failure (HF), five studies
      provided data for plasma MMP-2; the SMD between 321 hypertensive patients with
      and 334 hypertensive patients without HF was 2.36 units (P < 0.01). The
      heterogeneity among studies was high. CONCLUSIONS: These results suggest that MMP
      2, MMP-9 and TIMP-1 may have a role as biomarkers of cardiovascular remodeling in
      hypertension. If these results are confirmed in prospective clinical studies,
      they could provide new tools to stratify cardiovascular risk in hypertensive
      patients.

PMID- 22134385
TI  - Hypertension prevalence, awareness, treatment and control among older people in
      Latin America, India and China:  a 10/66 cross-sectional population-based survey.
AB  - OBJECTIVES: To estimate the prevalence, social patterning, treatment and control
      of hypertension among older people in the 10/66 Dementia Research Group
      developing country sites. METHODS: Cross-sectional surveys of SBP, hypertension,
      and hypertension awareness, treatment and control among 17 014 people aged 65
      years and over in eight urban and four rural sites in Latin America, India and
      China. RESULTS: Hypertension prevalence was higher in urban (range 52.6-79.8%)
      than rural sites (range 42.6-56.9%), and lower in men than women [pooled
      prevalence ratio 0.89, 95% confidence interval (CI) 0.85-0.93]. Educational
      attainment was positively associated with hypertension in rural and least
      developed sites. Age-standardized morbidity ratios, compared to USA (100), were
      higher in urban sites in Cuba (105), Dominican Republic (109), and Venezuela
      (107), similar in Puerto Rico (105), urban Mexico (99) and urban India (101), and
      lower in urban (75) and rural (61) Peru, rural Mexico (81), urban (91) and rural
      (84) China and rural India (65). In most Latin American centres, and urban China
      just over one-third of those with hypertension were controlled (BP < 140/90).
      Control was poor in rural China (2%), urban India (12%) and rural India (9%). The
      proportion controlled, not compositional factors (age, sex, education and
      obesity), explained most of the between-site variation in SBP. CONCLUSION:
      Uncontrolled hypertension is common among older people in developing countries,
      and may rise further during the demographic and health transitions. It is a major
      determinant of population SBP level. Strengthening primary care to improve
      hypertension management is necessary for primary prevention.

PMID- 22134386
TI  - Aliskiren inhibits atherosclerosis development and improves plaque stability in
      APOE*3Leiden.CETP transgenic mice with or without treatment with atorvastatin.
AB  - OBJECTIVE: Aliskiren is the first commercially available, orally active, direct
      renin inhibitor approved to treat hypertension. The renin-angiotensin system has
      been shown to be a significant contributor to the development of
      hypercholesterolemia-induced atherosclerosis. The aim of this study was to
      evaluate the antiatherosclerotic and plaque stabilization effects of aliskiren
      alone and in combination with atorvastatin. METHODS: APOE*3Leiden.CETP mice (n =
      14-17/group) were fed a western-type diet (containing 0.25% cholesterol) alone or
      were treated with either aliskiren (15 mg/kg per day), atorvastatin (3.6 mg/kg
      per day) or a combination of aliskiren and atorvastatin. Effects on SBP, total
      cholesterol, inflammation markers and atherosclerotic size and composition were
      assessed. RESULTS: Aliskiren reduced SBP (-19%, P < 0.001) and atorvastatin
      reduced total cholesterol (-24%, P < 0.001). Atherosclerotic lesion area was
      reduced by aliskiren (-40%, P < 0.01), atorvastatin (-61%, P < 0.001) and the
      combination treatment (-69%, P < 0.001). Aliskiren alone and together with
      atorvastatin decreased the number of T cells in the aortic root area (-60%, P <
      0.01; -41%, P < 0.05), as well as macrophage (-64%, P < 0.001; -72%, P < 0.001)
      and necrotic area (-52%, P = 0.071; -84%, P < 0.001) in the lesion. Atorvastatin
      alone and together with aliskiren decreased monocyte adherence (-43%, P < 0.05
      and -51%, P < 0.01) and monocyte chemoattractant protein-1 (both -36%, P < 0.01).
      The combination treatment decreased the number of lesions (-17%, P < 0.05) and E
      selectin (-17%, P < 0.05). CONCLUSION: Aliskiren inhibited atherosclerosis
      development and improved plaque stability alone and in combination with
      atorvastatin, possibly via a mechanism involving T cells. These results suggest a
      potential benefit of using aliskiren in a clinical setting, particularly in
      combination with statin treatment.

PMID- 22134387
TI  - Association of central and peripheral pulse pressure with intermediate
      cardiovascular phenotypes.
AB  - OBJECTIVE: We assessed the relationship between pulse pressure and intermediate
      cardiovascular phenotypes in a middle-aged cohort with high prevalence of
      hypertension. BACKGROUND: It has been suggested that central pulse pressure (cPP)
      is a better predictor of cardiovascular outcome than peripheral pulse pressure
      (pPP), particularly in the elderly. Yet, it is unclear if cPP provides additional
      prognostic information to pPP in younger individuals. METHODS: In 535 individuals
      we assessed cPP and pPP as well as the intermediate cardiovascular phenotypes
      pulse wave velocity (PWV; SphygmoCor, Complior, PulsePen), carotid intima-media
      thickness (C-IMT; carotid ultrasound), left-ventricular mass index (LVMI;
      echocardiography) and urinary albumin : creatinine ratio (ACR). cPP was derived
      noninvasively from brachial blood pressure by pulse wave analysis (PWA;
      SphygmoCor) based on radial pulse wave tonometry and a validated transfer
      function. RESULTS: The cohort contained 331 hypertensive participants of whom 84%
      were treated. The average age was 46 +/- 16 years. When compared to pPP, cPP had
      stronger associations with PWV (r = 0.471 vs. r = 0.372; P < 0.01), C-IMT (r =
      0.426 vs. r = 0.235; P < 0.01) and LVMI (r = 0.385 vs. r = 0.189; P < 0.01), but
      equal association with ACR (r = 0.236 vs. r = 0.226; P = n.s.). In contrast,
      after adjustment for age, mean arterial pressure, heart rate and hypertension
      status there was no significant difference between cPP and pPP for prediction of
      PWV (adjusted R, 0.399 vs. 0.413; P = 0.066), C-IMT (adjusted R, 0.399 vs. 0.413;
      P = 0.487) and LVMI (adjusted R, 0.181 vs. 0.170; P = 0.094) in multivariate
      analysis. CONCLUSION: In our middle-aged cohort with high prevalence of
      hypertension cPP is more closely correlated with cardiovascular phenotypes than
      pPP. When adjusted for relevant cofactors, however, cPP does not provide
      additional information beyond pPP.

PMID- 22134388
TI  - Effect of felodipine with irbesartan or metoprolol on sexual function and
      oxidative stress in women with essential hypertension.
AB  - OBJECTIVE: To evaluate the impact of felodipine with irbesartan on sexual
      function compared with felodipine with metoprolol in hypertensive women. METHODS:
      This was a prospective, randomized, parallel, active-controlled, open-label study
      (ClinicalTrials.org: NCT01238705) in 160 women (18-60 years) with mild or
      moderate hypertension, randomized to a once-daily treatment with felodipine
      combined with irbesartan or metoprolol for 48 weeks. Patients' sexual function
      was evaluated using a female sexual function index (FSFI) questionnaire at
      baseline and after 24 and 48 weeks of therapy. Levels of serum estradiol,
      testosterone, 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE) and
      malondialdehyde (MDA) were measured. RESULTS: The two combination regimens were
      similarly effective in lowering blood pressure. After 48 weeks, in felodipine
      irbesartan group, total scores of FSFI improved (P < 0.001). Items showing
      improvement in scores corresponded to desire, arousal and orgasm (P < 0.001; P =
      0.002; P = 0.049, respectively). Levels of estradiol increased under treatment
      with felodipine-irbesartan (P = 0.003) and decreased under felodipine-metoprolol
      treatment (P < 0.001). The concentration of testosterone declined after
      felodipine-irbesartan therapy (P < 0.001) and increased under felodipine
      metoprolol treatment (P < 0.001). In the felodipine-irbesartan group, decreases
      of 8-OHdG, 4-HNE (P < 0.001) and MDA (P < 0.001) were observed. The felodipine
      irbesartan combination resulted in less oxidative stress. The differences in
      changes in 8-OHdG, 4-HNE and MDA between the two groups were significant (P <
      0.05). CONCLUSION: These results suggested that the felodipine-irbesartan
      combination regimen improved sexual function in hypertensive women, whereas
      felodipine-metoprolol regiment did not. The reason for the different influence of
      these two combination therapy on female sexual function might be their different
      impacts on oxidative stress and hormone levels.

PMID- 22134389
TI  - Rotating night shift work and disparate hypertension risk in African-Americans.
AB  - OBJECTIVE: Hypertension disproportionally affects black compared with white
      Americans, even after accounting for known risk factors. Circadian disruption as
      encountered by rotating night shift workers has been associated with an increased
      risk for hypertension. Because blood pressure responds differently to sleep
      alterations in blacks compared with whites, we hypothesized that rotating night
      shift work may be a stronger risk factor for hypertension among blacks. METHODS:
      We prospectively examined the association between rotating night shift work and
      the risk of hypertension in 1510 black and 94 142 white female participants of
      the Nurses' Health Study II who were nonhypertensive at baseline in 1991. We used
      Cox proportional hazards models to control for potential confounders. RESULTS:
      During 16 years of follow-up (1991-2007), we identified 580 incident cases of
      hypertension in blacks and 23 360 cases in whites. In blacks, the multivariable
      hazard ratio for incident hypertension among women who worked rotating night
      shift for more than 12 months in the previous 2 years was 1.81 [95% confidence
      interval (CI) 1.14-2.87], compared with those working none. By contrast, in
      whites, we observed no increase in risk (hazard ratio 0.99, 95% CI 0.93-1.06).
      The association between shift work and hypertension varied significantly by race
      (P interaction = 0.01). In secondary analyses, the multivariable hazard ratio for
      incident hypertension in black women who ever performed rotating night shift work
      was 1.46 (95% CI 1.07-1.99), compared with those never working rotating night
      shifts. In whites, there was no increase in risk (hazard ratio 0.97, 95% CI 0.93
      1.01) (P interaction < 0.01). CONCLUSION: Rotating night shift work is
      independently associated with an increased risk of hypertension in blacks but not
      in whites.

PMID- 22134390
TI  - Classes of antihypertensive medications and blood pressure control in relation to
      metabolic risk factors.
AB  - OBJECTIVE: Metabolic syndrome (MetS) is associated with uncontrolled blood
      pressure (BP), despite use of aggressive therapy. This study was performed to
      assess whether the use of different classes of antihypertensive drugs might
      influence this association. METHODS: We evaluated risk of uncontrolled BP (BP >=
      140/90 mmHg under antihypertensive treatment) at the time of the last available
      visit, after a mean follow-up of 5 years in 4612 hypertensive patients without
      prevalent cardiovascular disease (43% women, 53 +/- 11 years) from the Campania
      Salute Network. RESULTS: At the time of the first visit, prevalence of MetS was
      associated with 43% increased risk of follow-up uncontrolled BP, independent of
      significant confounders and without a significant impact of specific classes of
      antihypertensive medications. At the time of the last available visit, patients
      with MetS had more often uncontrolled BP, despite more aggressive treatment.
      After adjusting for demographics, risk factors and number of antihypertensive
      medications, risk of uncontrolled BP was reduced with increased prescription of
      diuretics [DRTs; odds ratio (OR) 0.73, 95% confidence interval (CI) 0.62-0.86],
      renin-angiotensin system blockers [RAS-blockers (Angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers); OR 0.77, 95% CI 0.66-0.91] and
      statins (OR 0.79, 95% 0.68-0.92, all P < 0.05), without significant impact of the
      other classes of medications. CONCLUSION: Despite the use of increased number of
      medications, hypertensive patients with MetS are at higher risk of uncontrolled
      BP. Among classes of antihypertensive medications, increased prescriptions of
      DRTs, RAS-blockers and also statins decrease the probability of poor BP control.

PMID- 22134391
TI  - The association between preeclampsia and arterial stiffness.
AB  - A systematic review and meta-analysis was conducted using MEDLINE, EMBASE, and
      the Cochrane Library to investigate the association between preeclampsia and
      arterial stiffness. Twenty-three relevant studies were included. A significant
      increase in all arterial stiffness indices combined was observed in women with
      preeclampsia vs. women with normotensive pregnancies [standardized mean
      difference 1.62, 95% confidence interval (CI) 0.73-2.50]; carotid-femoral pulse
      wave velocity (cfPWV) and augmentation index (AIx) were also significantly
      increased (weighted mean difference, WMDcfPWV 1.04, 95% CI 0.34-1.74; WMDAIx
      15.10, 95% CI 5.08-25.11), whereas carotid-radial PWV (crPWV) increase did not
      reach significance (WMDcrPWV 0.99, 95% CI -0.07 to 2.05). Significant increases
      in arterial stiffness measurements were noted in women with preeclampsia compared
      with those with gestational hypertension. Arterial stiffness measurements may
      also be useful in predicting preeclampsia and may play a role in the increased
      risk of future cardiovascular complications seen in women with a history of
      preeclampsia.

PMID- 22134392
TI  - Efficacy of isolated home blood pressure monitoring for blood pressure control: 
      randomized controlled trial with ambulatory blood pressure monitoring - MONITOR
      study.
AB  - BACKGROUND: Rates of control of hypertension remain unsatisfactory worldwide and
      simple methods to encourage patients to adhere to treatments are still necessary.
      In this randomized controlled trial, we evaluated the efficacy of a protocol of
      home blood pressure monitoring (HBPM), without medication titration, to improve
      BP assessed by ambulatory BPM (ABPM). METHODS: Patients with hypertension under
      drug treatment and with uncontrolled BP at office and by 24-h ABPM were randomly
      assigned to HBPM or usual care. The treatment was not modified during the trial.
      Follow-up visits were conducted at 7 and 30 days after randomization, and at 60
      days to assess the outcome. Deltas between baseline and final ABPM measurements
      were calculated for 24-h, nightly and daily ambulatory SBP and DBP. RESULTS: Of
      558 patients screened, 136 fulfilled the eligibility criteria and were
      randomized, and 121 (89%) completed the trial. The between groups deltas (95%
      confidence interval) of variation of 24 h, nightly and daily SBP were 5.4 (0.9
      9.8) (P = 0.018), 10.9 (2.9-18.9) (P = 0.012) and 4.4 mmHg (-0.1 to 8.8) (P =
      0.055), respectively; the corresponding deltas for DBP were 4.5 (1.6-7.4) (P =
      0.003), 3.4 (0.4-6.3) (P = 0.025) and 5.8 mmHg (2.5-9.0) (P = 0.001),
      respectively. At the end of the trial, 32.4% of patients of the HBPM groups and
      16.2% of the control group had 24-h SBP less than 130/80 mmHg (P = 0.03).
      CONCLUSION: A protocol of HBPM without medication titration enhances the control
      of BP assessed by ABPM.

PMID- 22134393
TI  - Bony avulsion of the supraspinatus origin from the scapular spine.
AB  - We describe a case of an avulsion of the scapular spine at the origin of the
      supraspinatus muscle, with successful conservative treatment. An isolated
      avulsion is rare, as most avulsions occur in combination with other (more severe)
      injuries such as fractures of the scapula body or neck, coracoid process, glenoid
      or humerus. These injuries are mostly seen in high-energy trauma cases and need
      their own specific treatment. One should therefore always rule out concurrent
      trauma before treating conservatively.

PMID- 22134394
TI  - Letter from the editor: renaming the journal Human Vaccines & Immunotherapeutics.

PMID- 22134395
TI  - Human vaccines & immunotherapeutics.

PMID- 22134397
TI  - Determinants of heart failure self-care: a systematic literature review.
AB  - Self-care is an important aspect of heart failure (HF) management. Information on
      the determinants of self-care is necessary for the development of self-care
      promotion interventions. HF self-care includes self-care management, self-care
      maintenance, sodium, fluid and alcohol intake restriction, physical activity,
      smoking cessation, monitoring signs and symptoms and keeping follow-up
      appointments. To assess the evidence regarding presumed determinants of HF self
      care and make recommendations for interventions to promote self-care behavior
      among HF patients, a systematic literature review was conducted. Based on
      inclusion and exclusion criteria and a quality assessment, twenty-six articles
      were included. A best evidence synthesis was used. Results showed that the length
      of time since patients' diagnosis with HF is positively related to their
      performance of self-care maintenance. Moreover, it was found that HF patients'
      perceived benefits and barriers are related to their restriction of sodium
      intake, and that patients with type-D personality are less likely to consult
      medical professionals. There was also evidence for a few non-significant
      relationships. All other evidence was inconsistent, mainly due to insufficient
      evidence. Interventions that aim to increase the performance of self-care
      maintenance can teach newly diagnosed patients the skills that are usually
      attained with experience acquired as a result of living with HF for a longer
      time. Perceived benefits and barriers of restricting sodium intake could be
      targeted in interventions for sodium intake reduction among HF patients. Finally,
      interventions for the promotion of adequate consulting of medical professionals
      can specifically target HF patients with a type-D personality.

PMID- 22134398
TI  - Protective effect of salidroside from Rhodiolae Radix on diabetes-induced
      oxidative stress in mice.
AB  - It has been confirmed that diabetes mellitus (DM) carries increased oxidative
      stress. This study evaluated the effects of salidroside from Rhodiolae Radix on
      diabetes-induced oxidative stress in mice. After induction of diabetes, diabetic
      mice were administered daily doses of 50, 100 and 200 mg/kg salidroside for 28
      days. Body weights, fasting blood glucose (FBG), serum insulin, TC (total
      cholesterol), TG (triglyceride), malondialdehyde (MDA), superoxide dismutase
      (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured. Results
      showed that salidroside possessed hypoglycemic activity and protective effects
      against diabetes-induced oxidative stress, which could significantly reduce FBG,
      TC, TG and MDA levels, and at same time increase serum insulin levels, SOD, GPx
      and CAT activities. Therefore, salidroside should be considered as a candidate
      for future studies on diabetes.

PMID- 22134399
TI  - Antimicrobial activity of Piper gaudichaudianum Kuntze and its synergism with
      different antibiotics.
AB  - One of the oldest forms of medical practice is the use of plants for the
      treatment and prevention of diseases that affect humans. We have studied the
      antimicrobial activity and synergism of Piper gaudichaudianum Kuntze with
      different antibiotics. The crude extract from the leaves of P. gaudichaudianum
      was submitted to chromatographic separation, resulting in five fractions.
      Fraction F3 contained a chromone (2,2-dimethyl-6-carboxycroman-4-one), and
      fraction F2 contained isomers that are prenylated derivatives of benzoic acid [4
      hydroxy-(3',7'-dimethyl-1'-oxo-octa-E-2'-6'-dienyl)benzoic acid and 4-hydroxy
      (3',7'-dimethyl-1'-oxo-octa-2'-Z-6'-dienyl) benzoic acid]. The chemical
      structures of both compounds were determined by analysis of 1H-NMR, 13C-NMR,
      COZY, DEPT, HMQC, and HMBC spectral data, and by comparison with data in the
      literature. The crude extract, fraction F2, and fraction F3 showed good activity
      against Staphylococcus aureus, Bacillus subtilis, and Candida tropicalis. The two
      benzoic acid derivatives only showed activity against S. aureus and B. subtilis.
      The bioauthographic analysis showed an inhibition zone only in fraction F2.
      Fractions F2 and F3 showed synergism in combination with ceftriaxone,
      tetracycline, and vancomycin. Morphological changes in form and structure were
      found by scanning electron microscopy in S. aureus treated with the combination
      of fraction F2 with vancomycin.

PMID- 22134400
TI  - The triterpenes 3beta-lup-20(29)-en-3-ol and 3beta-lup-20(29)-en-3-yl acetate and
      the carbohydrate 1,2,3,4,5,6-hexa-O-acetyl-dulcitol as photosynthesis light
      reactions inhibitors.
AB  - Three compounds were isolated from Maytenus acanthophylla Reissek (Celastraceae):
      the pentacyclic triterpenes lup-20(29)-en-3beta-ol (lupeol, 1) and 3beta-lup
      20(29)-en-3-yl acetate (2) and the carbohydrate 1,2,3,4,5,6-hexa-O-acetyldulcitol
      (3); lupeol was also isolated from Xylosma flexuosa. The compounds' structures
      were elucidated by spectroscopic and spectrometric analysis. Compound 1 acts as
      an energy transfer inhibitor, interacting with isolated CF1 bound to thylakoid
      membrane, and dulcitol hexaacetate 3 behaves as a Hill reaction inhibitor and as
      an uncoupler, as determined by polarography. Chlorophyll a (Chl a) fluorescence
      induction kinetics from the minimum yield F0 to the maximum yield F(M )provides
      information of the filling up from electrons coming from water to plastoquinone
      pool with reducing equivalents. In this paper we have examined the effects of
      compounds 1 and 3 on spinach leaf discs. Compound 1 induces the appearance of a K
      band, which indicates that it inhibits the water splitting enzyme. In vivo assays
      measuring the fluorescence of chl a in P. ixocarpa leaves sprayed with compound
      1, showed the appearance of the K-band and the PSII reaction centers was
      transformed to "heat sinks" or silent reaction centers unable to reduce Q(A).
      However, 3 also induced the appearance of a K band and a new band I appears in P.
      ixocarpa plants, therefore it inhibits at the water splitting enzyme complex and
      at the PQH2 site on b6f complex. Compounds 1 and 3 did not affect chlorophyll a
      fluorescence of L. perenne plants.

PMID- 22134401
TI  - Structural and molecular characterization of meso-substituted zinc porphyrins: a
      DFT supported study.
AB  - Structural parameters of a range of over 100 meso-substituted zinc porphyrins
      were reviewed and compared to show how far the nature of the functional group may
      affect the interatomic distances and bond angles within the porphyrin core. It
      was proved that even despite evident deformations of the molecular structure,
      involving twisting of the porphyrin's central plane, the coupled pi-bonding
      system remains flexible and stable. DFT calculations were applied to a number of
      selected porphyrins representative for the reviewed compounds to emphasize the
      relevance of theoretical methods in structural investigations of complex
      macrocyclic molecular systems. Experimental and DFT-simulated IR spectral data
      were reported and analyzed in context of the individual molecular features
      introduced by the meso substituents into the porphyrin moiety base. Raw
      experimental spectral data, including 1H- and 13C-NMR, UV-Vis, FTIR, XRD, and
      other relevant physicochemical details have been provided for a specially chosen
      reference zinc porphyrin functionalized by tert-butylphenyl groups.

PMID- 22134402
TI  - Glaucoma associated with Boston type I keratoprosthesis.
AB  - PURPOSE: To evaluate outcomes of the Boston type I keratoprosthesis (KPro) and
      associated incidence of glaucoma. DESIGN: Retrospective cohort study.
      PARTICIPANTS: All patients who underwent KPro surgery at 1 institution from 2003
      to 2009 with at least 3 months of follow-up. METHODS: Preoperative visual acuity,
      diagnosis, history of glaucoma, and intraoperative and postoperative parameters
      were recorded. Statistical analysis was performed to identify factors that may
      influence increase in intraocular pressure (IOP) and glaucoma development or
      progression after surgery. MAIN OUTCOME MEASURES: Best-corrected visual acuity
      (BCVA), IOP, postoperative medical and surgical treatments for glaucoma, and KPro
      retention and complications. RESULTS: Thirty-six KPro procedures were performed
      in 30 eyes of 29 patients with a mean (+/-SD) follow-up of 17 +/- 19 months
      (range, 3-67 months). The main indication for KPro implantation was corneal graft
      failure (77%). Primary KPro procedures were performed in 23% of eyes for limbal
      stem cell deficiency secondary to chemical burns and aniridia and for herpetic
      disease. Median preoperative BCVA was hand motions with an overall improvement to
      20/330 (range, 20/20 to hand motions) at 9 months postoperatively; mean BCVA was
      20/600 (range, 20/40 to NLP) at the last follow-up. Twenty eyes (67%) had a
      preoperative history of glaucoma, with 8 of those eyes (40%) having undergone
      previous glaucoma surgery. Twenty-one eyes (70%) underwent concomitant glaucoma
      surgery. Postoperative increased IOP (22 mm Hg or higher) was noted in 15 eyes
      (50%), although definite glaucoma development or progression was noted in 7 of
      those 15 eyes (23% of total eyes). Mean BCVA at the last follow-up in eyes with
      glaucoma development or progression was 3/200 compared with 20/563 in the
      remaining 23 eyes. Six patients (20%) required repeat KPro implantation, and
      retroprosthetic membranes developed in 23 eyes (77%). No patient had vitritis or
      infectious endophthalmitis develop. CONCLUSIONS: The Boston type I KPro is an
      effective option for management of eyes with poor prognosis for primary or repeat
      penetrating keratoplasty. Visual potential is limited by preoperative
      comorbidities; however, glaucoma development or progression of preexisting
      glaucoma is a significant cause of postoperative visual loss. Rigorous
      perioperative management of elevated IOP is essential for long-term success of
      KPro surgery.

PMID- 22134403
TI  - Are the surgeons safe during UV-A radiation exposure in collagen cross-linking
      procedure?
AB  - PURPOSE: To quantify the effect of scattered UV-A radiation used in the collagen
      cross-linking (CXL) procedure and the amount of radiation reaching the surgeon
      and the surrounding area and to estimate the dampening effect by various
      protective devices. METHODS: In this case series, 3 patients [aged 25-30 (+/-2.5)
      years] with keratoconus underwent a CXL procedure with UV-A light and riboflavin.
      Irradiance was measured using a spectrometer (Model USB2000; Ocean Optics, Inc)
      for various distances from the source, at various angles, and for different
      durations of radiation. The spectrometer was also used to measure the dampening
      effect produced by gown, latex gloves, and UV-protective glasses. RESULTS:
      Maximum UV-A radiation (1.4 * 10(-9) mW/cm(2)) was measured at 2 cm from the
      limbus, when the probe was held at a 45-degree angle to the floor. UV-A radiation
      reaching the surgeon's eye and the abdomen was 3.403 * 10(-11) and 2.36 * 10(-11)
      mW/cm(2), respectively. Gown, latex gloves, and UV-protective glasses showed
      dampening effects of 99.58%, 95.01%, and 99.73%, respectively. CONCLUSIONS: CXL
      appears to be a safe procedure with respect to UV-A radiation exposure to the
      surgeon. Further safety can be ensured by UV-protective devices.

PMID- 22134404
TI  - Ocular disorders due to eyelash extensions.
AB  - PURPOSE: Eyelash extensions are a beauty treatment in which individual synthetic
      extensions are applied, lash by lash, to natural eyelashes. The procedure is
      becoming popular worldwide because they seem more natural and last longer than
      other types of false eyelashes. However, partly because a bonding agent (glue)
      containing organic substances is applied near the eyes, consultations with
      ophthalmologic clinics and the National Consumer Affairs Center of Japan have
      increased annually. In the present study, we investigated eye disorders due to
      eyelash extensions. METHODS: Ocular disorders were retrospectively investigated
      in 107 women (age 21-52 years) who visited ophthalmologic clinics in Japan with
      complaints of eye symptoms resulting from eyelash extensions between March 2007
      and March 2010. The patients had no history of eye diseases. Of the patients 42
      were 21 to 29 years of age, 44 were 30 to 39 years, 19 were 40 to 49 years, and 2
      were 50 to 60 years. Three glues, the ingredients of which are not disclosed,
      were chemically analyzed for detection of more than 70 substances suspected to be
      ingredients. RESULTS: The ocular disorders due to eyelash extensions included
      keratoconjunctivitis due to invasion of glue or removing agents in 64 patients,
      allergic blepharitis due to glues in 42 patients (4 of these patients developed
      both keratoconjunctivitis and allergic blepharitis), conjunctival erosion due to
      eyelid-fixing tapes in 3 patients, allergic blepharitis due to eyelid-fixing
      tapes in 1 patient, and subconjunctival hemorrhage due to compression during
      removal of extensions in 1 patient. In all 107 patients, the symptoms were
      resolved by adequate treatments with eye drops and/or ointments. Ingredient
      analysis detected formaldehyde in concentrations above the standard threshold
      level in all 3 glues. In addition, lead and benzoic acid were also detected;
      however, concentrations of these particular compounds were low and therefore
      unlikely to cause disorders in humans. CONCLUSIONS: Eyelash extension procedures
      may cause ocular disorders, such as keratoconjunctivitis and allergic
      blepharitis; indeed, all glues for eyelash extensions analyzed in the present
      study contained formaldehyde, which can cause keratoconjunctivitis. From the
      viewpoint of hygienics, it is necessary to disinfect devices, provide handling
      instructions for organic solvents, improve glue ingredients, and improve the
      ophthalmologic knowledge of the practitioners.

PMID- 22134406
TI  - Temperature-directed structural recurrence in low-symmetric Co(II) complexes and
      nanocrystals.
AB  - Low-symmetric complexes {[Co(MU(2)-L)(H(2)O)(2)].H(2)O}(n) (1) and {[Co(MU(3)
      L)(H(2)O)].0.5H(2)O}(n) (2) and corresponding nanocrystals were obtained, which
      exhibit structural recurrence behaviour at various temperatures as well as
      changes of chiral, nonlinear optical and ferroelectric properties.

PMID- 22134407
TI  - Apoptotic effect of Vibrio vulnificus cytolysin on A549 human lung adenocarcinoma
      cells.
AB  - Vibrio vulnificus cytolysin (VVC) has a very strong cytotoxic effect on various
      types of mammalian cells. However, the inhibitory effect of VVC on the
      proliferation of human lung cancer cells has scarcely been reported. This study
      aimed to analyze the effects of recombinant VVC (rVVC) on the A549 human lung
      adenocarcinoma cell line and to investigate the underlying molecular mechanisms
      governing these effects. This study showed that rVVC inhibited the proliferation
      of A549 cells in a concentration- and time-dependent manner (as measured by the
      MTT assay). rVVC failed to induce the release of intracellular lactate
      dehydrogenase (LDH) from the target cells suggesting that osmotic lysis may not
      contribute to its cytolysin-induced cytotoxicity. Treatment of A549 cells with an
      IC50 (concentration of drug that inhibits cell growth by 50%) of rVVC resulted in
      morphological changes and blebbing typical of apoptosis. Annexin-V FITC analysis
      by FCM indicated that rVVC-induced apoptosis in A549 cells occurs in a dose
      dependent manner. A DNA fragmentation assay was utilized to investigate the
      apoptosis induced by rVVC. The pro-apoptotic activity of rVVC was attributed to
      its ability to modulate, in a concerted manner, the expression of Bcl-2 and Bax
      proteins, which were down- and up-regulated, respectively. Caspase-9 and -3 were
      subsequently activated, however caspase-8 was not. These results prove that rVVC
      effectively induces programmed cell death and suggests that rVVC-induced
      apoptosis in the A549 cell line is mediated by the regulation of Bcl-2 protein
      expression and the activation of caspase-9 and -3.

PMID- 22134408
TI  - The effect of tibial tuberosity realignment procedures on the patellofemoral
      pressure distribution.
AB  - PURPOSE: The study was performed to characterize the influence of tibial
      tuberosity realignment on the pressure applied to cartilage on the patella in the
      intact condition and with lesions on the lateral and medial facets. METHODS: Ten
      knees were loaded in vitro through the quadriceps (586 N) and hamstrings (200 N)
      at 40 degrees , 60 degrees , and 80 degrees  of flexion while measuring
      patellofemoral contact pressures with a pressure sensor. The tibial tuberosity
      was positioned 5 mm lateral of the normal position to represent lateral
      malalignment, 5 mm medial of the normal position to represent tuberosity
      medialization, and 10 mm anterior of the medial position to represent tuberosity
      anteromedialization. The knees were tested with intact cartilage, with a 12-mm
      diameter lesion created within the lateral patellar cartilage, and with the
      lateral lesion repaired with silicone combined with a medial lesion. A repeated
      measures ANOVA and post hoc tests were used to identify significant (P < 0.05)
      differences in the maximum lateral and medial pressure between the tuberosity
      positions. RESULTS: Tuberosity medialization and anteromedialization
      significantly decreased the maximum lateral pressure by approximately 15% at 60
      degrees  and 80 degrees  for intact cartilage and cartilage with a lateral
      lesion. Tuberosity medialization significantly increased the maximum medial
      pressure for intact cartilage at 80 degrees , but the maximum medial pressure did
      not exceed the maximum lateral pressure for any testing condition. CONCLUSIONS:
      The results indicate that medializing the tibial tuberosity by 10 mm reduces the
      pressure applied to lateral patellar cartilage for intact cartilage and cartilage
      with lateral lesions, but does not overload medial cartilage.

PMID- 22134409
TI  - Local anaesthetics and chondrotoxicty: What is the evidence?
AB  - PURPOSE: Recent reports have suggested that local anaesthetic agents have a toxic
      effect on articular chondrocytes. This is despite the widespread intra-articular
      use of local anaesthetic agents following arthroscopic procedures for a number of
      years. METHODS: We have reviewed the available basic science literature focusing
      on the studies assessing the effect of exposing articular chondrocytes to local
      anaesthetic agents. We attempt to highlight the key findings and, where possible,
      extrapolate the laboratory findings to the operating theatre. RESULTS: Basic
      science reports are analysed according to their setting of either in vitro, ex
      vivo or in vivo and according to cell line. A majority of work to date has been
      done using in vitro models. Only a small number of in vivo models using animal
      cell lines have been used and the best of these have conflicting results with
      regard lasting toxicity secondary to local anaesthetic exposure. CONCLUSIONS:
      Numerous reports suggest a toxic effect of local anaesthetic agents on articular
      chondrocytes, however, further work is warranted to establish the precise
      mechanism of toxicity and whether or not single bolus administration results in
      long-term deleterious outcomes. Determining the ideal in vitro model will help in
      extrapolating laboratory data to the operating theatre.

PMID- 22134411
TI  - Intrajugular balloon catheter for prevention of air embolism.

PMID- 22134410
TI  - Potentially inappropriate medication in geriatric patients: the Austrian
      consensus panel list.
AB  - BACKGROUND: The practice of inappropriate medication and drug prescription is a
      major risk factor for adverse drug reactions in geriatric patients and increases
      the individual, as well as overall, rates of hospital admissions, resulting in
      increased health care expenditures. A consensus-based list of drugs, generally to
      be avoided in geriatric patients, is a practical tool to possibly improve the
      quality of prescribing. OBJECTIVE: The aim was to develop a consensus-based list
      of potentially inappropriate medications (PIM) for geriatric patients in Austria.
      Local market characteristics and documented prescribing regimens were considered
      in detail. METHODS: A two-round Delphi process involving eight experts in the
      field of geriatric medicine was undertaken to create a list of potentially
      inappropriate medications. Using a 5-point Likert scale (from strong agreement to
      strong disagreement), mean ratings from the experts were evaluated for each drug
      selected in the first round. The participants were first asked to comment on the
      potential inappropriateness of a preliminary list of drugs, and to propose
      alternate substances missing in the previous questionnaire for a second rating
      process. All drugs whose upper limit of the 95% CI was less than 3.0 were
      classified as potentially inappropriate. Drugs with a 95% CI enclosing 3.0
      entered a second rating by the experts, in addition to other substances suggested
      during the first questionnaire. Drugs in the second rating were evaluated in
      comparable fashion to the first one. The final list was synthesized from the
      results in both rounds. RESULTS: Out of a preliminary list of 102 drugs, 61 drugs
      (59.2%) were classified as potentially inappropriate for geriatric persons in the
      first Delphi- round. In the second rating, six drugs that were reevaluated, and
      six drugs proposed additionally, were rated as potentially inappropriate. The
      final list contains 73 drugs to be avoided in older patients because of an
      unfavorable benefit/risk profile and/or unproven effectiveness. The list also
      contains suggestions for therapeutic alternatives and information about
      pharmacological and pharmacokinetic characteristics of all drugs judged as
      potentially inappropriate. CONCLUSION: The current Austrian list of potentially
      inappropriate medications may be a helpful tool for clinicians to increase the
      quality of prescribing in older patients. Like all explicit lists previously
      published, its validity needs to be proven in validation studies.

PMID- 22134412
TI  - "Externally reinforced endotracheal tube" in a pediatric neurosurgical patient.

PMID- 22134413
TI  - The potential of quantified lower cranial nerve EMG for monitoring of anesthetic
      depth.
AB  - BACKGROUND: During surgery, lower cranial nerve (CN) electromyography (EMG) may
      show spontaneous activity without surgical correlate. These episodes have been
      observed in association with sudden patient movement. In the study presented,
      this activity was quantified and correlated to the Bispectral Index (BIS) to
      evaluate the potential of lower CN-EMG for monitoring the depth of anesthesia.
      METHODS: Spontaneous EMG activity in muscles targeted by the CNs IX, X, and XII
      was quantified and correlated with the BIS measured in 23 patients operated on
      for posterior fossa pathology. In a blinded retrospective analysis, the time
      interval from beginning of build-up of the respective parameter (EMG activity and
      BIS) until extubation was marked. The resulting time intervals were then compared
      between BIS and EMG. RESULTS: EMG and BIS build-up was seen 12.3 and 5.9 minutes,
      respectively, before extubation in median. Thus, EMG provided a longer "warning
      time" (P=0.026). Isolated lower CN EMG channels preceded BIS in 53%, 62%, and 70%
      (CN IX, X, and XII). The earliest available EMG channel preceded BIS in 67% of
      the patients by a median time of 4.3 minutes. The beginning of EMG build-up in
      the earliest channel was found to be significantly earlier than BIS (P<0.001).
      CONCLUSIONS: Spontaneous EMG of muscles targeted by lower CNs seems to correlate
      well with arousal reactions at the end of anesthesia. In many cases, this effect
      preceded BIS changes. Thus, lower CN EMG monitoring may be a valuable tool in
      monitoring adequate depth of anesthesia.

PMID- 22134414
TI  - The reaction of beta-lactam carbenes with 3,6-dipyridyltetrazines: switch of
      reaction pathways by 2-pyridyl and 4-pyridyl substituents of tetrazines.
AB  - The reactions of beta-lactam carbenes with both 3,6-di(2-pyridyl)tetrazine and
      3,6-di(4-pyridyl)tetrazine were studied. It was found that beta-lactam carbenes
      reacted with 3,6-di(2-pyridyl)tetrazine to produce 5-triazolo[1,5-a]pyridylpyrrol
      2-ones in good yields, while with 3,6-di(4-pyridyl)tetrazine, they afforded
      pyrido[c]cyclopenta[b]pyrrol-2-ones in moderate yields. Both reactions were
      proposed to follow cascade mechanisms containing a 3,6a-dipyridylpyrrolo[3,2
      c]pyrazol-5-one intermediate. The different pathways of the transformation of
      pyrrolo[3,2-c]pyrazol-5-ones were switched by the 2- and 4-pyridyl substituents.
      This work not only provided a simple and efficient strategy for the construction
      of novel triazolo[1,5-a]pyridine and pyrido[c]cyclopenta[b]pyrrole derivatives,
      respectively, but also revealed two different thermal transformation patterns of
      3H-pyrazole compounds.

PMID- 22134415
TI  - Neurocutaneous melanosis associated with Dandy-Walker complex and an intracranial
      cavernous angioma.

PMID- 22134416
TI  - Acquired os odontoideum: a case report and literature review.

PMID- 22134417
TI  - Spontaneous intraventricular hemorrhage from low-grade optic glioma: case report
      and review of the literature.

PMID- 22134418
TI  - Exophytic third nerve schwannoma mimicking a mesial temporal intra-axial lesion:
      case report.

PMID- 22134419
TI  - Dental eruption sequence and eruption times in Erythrocebus patas.
AB  - Erythrocebus patas has a short inter-birth interval, juveniles become independent
      from their mother early, females are young at first birth, and adult females have
      a high mortality rate. According to Schultz's rule, the molars of fast-growing
      and shorter-lived primate species erupt early relative to the replacement teeth.
      Based on the life history of E. patas, we hypothesized that the molars would
      erupt before the replacement teeth and/or that the eruption time of its molars
      would be early. The purpose of the present study was to determine the dental
      eruption sequence and eruption times for E. patas and to test our hypothesis. The
      eruption sequence for the permanent teeth of E. patas is M1 I1 I2 M2 P3 P4 [C
      M3]/M1 I1 I2 M2 P4 [P3 C]M3 in males and M1 I1 I2 [M2 P4 P3 C]M3/M1 I1 I2 [M2 P4
      P3 C]M3 in females. Because these sequences constitute the general pattern seen
      in cercopithecines, Schultz's rule could not be applied to E. patas. The
      emergence time of upper and lower first molar (M1) is earlier in E. patas than in
      macaques, baboons, and mandrills and is similar to that in Chlorocebus aethiops.
      The emergence time of deciduous upper and lower fourth premolar (dp4) is similar
      to that in the above-mentioned cercopithecines but is later than that in Ch.
      aethiops. The emergence times of upper and lower second molar (M2) and upper and
      lower third molar (M3) in E. patas are earlier than those in the above-mentioned
      cercopithecines but later than those in Ch. aethiops. However, the intervals of
      the emergence time between each permanent molar in E. patas are similar to those
      of the above-mentioned cercopithecines. The early appearance of M2 and M3 in E.
      patas is related to the short interval of emergence time between dp4 and M1.

PMID- 22134420
TI  - Pharmacological explanation for the medicinal use of Juniperus excelsa in
      hyperactive gastrointestinal and respiratory disorders.
AB  - Crude extract of Juniperus excelsa (JeExt), which tested positive for the
      presence of anthraquinone, flavonoids, saponins, sterols, terpenes and tannin,
      exhibited a protective effect against castor oil-induced diarrhoea in mice at 100
      1000 mg/kg. In rabbit jejunum preparations, JeExt (0.01-1.0 mg/mL) caused
      relaxation of spontaneous and K(+) (80 mM)-induced contractions at similar
      concentrations to papaverine, whereas verapamil was relatively more potent
      against K(+). JeExt (0.03-0.3 mg/mL) shifted Ca(2+) concentration-response curves
      to the right, like papaverine or verapamil. JeExt (0.003-0.01 mg/mL) caused a
      leftward shift of isoprenaline-induced inhibitory concentration-response curves,
      similar to papaverine. JeExt (1.0-30 mg/kg) caused suppression of carbachol (CCh,
      100 MUg/kg)-induced increase in inspiratory pressure of anaesthetized rats. In
      guinea-pig trachea, JeExt (0.001-3.0 mg/mL) relaxed CCh (1 MUM)- and high K(+)
      induced contractions and shifted isoprenaline-induced inhibitory curves to the
      left. This study suggests that Juniperus excelsa possibly exhibits a combination
      of Ca(2+) antagonist and phosphodiesterase inhibitory effects, which provides a
      pharmacological basis for its traditional use in disorders of gut and airways
      hyperactivity, such as diarrhoea, colic and asthma.

PMID- 22134421
TI  - Emergency physicians' opinions on the use of intravenous fluids to treat patients
      intoxicated with ethanol (alcohol): attitudes of emergency medicine physicians in
      the North East of England toward the use of intravenous fluids to treat
      individuals intoxicated with ethanol (alcohol) attending the emergency department
      compared with the scientific evidence.
AB  - OBJECTIVES: There is an apparent conflict between published evidence and UK
      emergency medicine (EM) physician practice with regard to the use of intravenous
      fluids to treat patients intoxicated with alcohol. We conducted a survey of all
      EM physicians in North East (NE) England to determine opinion with regard to this
      therapy, and compared this with the available evidence for its benefit. METHODS:
      We identified 136 EM consultants and trainees in NE England. Each one was
      contacted and asked to complete a questionnaire with regard to their opinion on
      the use of intravenous fluids for intoxicated patients, both with and without
      head injury. RESULTS: The majority (73%) of EM physicians in the NE England use
      intravenous fluids in their treatment of intoxicated patients. The treatment used
      varies, but the most commonly used fluid is 0.9% saline (volume range, 500-3000
      ml; mean, 1300 ml). Fewer respondents (52%) would use intravenous fluids if the
      patient had suffered an apparent head injury. CONCLUSION: The use of intravenous
      fluids to treat intoxication is common practice among EM physicians in NE
      England. The available literature states that this practice is futile. However,
      there are significant limitations in these studies. This suggests that EM
      physicians might be using intravenous fluids therapy (IVT) because they are
      finding in their own practice it is effective. We hypothesize that IVT should
      improve care in most intoxicated patients as the result of a direct dilutional
      effect. Further research is required to establish the validity of existing EM
      physician's practice of using IVT.

PMID- 22134423
TI  - Highly ordered mesoporous Cr2O3 materials with enhanced performance for gas
      sensors and lithium ion batteries.
AB  - Highly ordered mesoporous Cr(2)O(3) materials with high specific surface area and
      narrow pore size distribution were successfully prepared by a vacuum assisted
      impregnation method. Both 2-dimensional hexagonal and 3-dimensional cubic
      Cr(2)O(3) mesoporous replicas from SBA-15 and KIT-6 templates exhibit enhanced
      performance for gas sensors and lithium ion batteries, compared to the bulk
      Cr(2)O(3) counterpart.

PMID- 22134422
TI  - Lansoprazole inhibits nitric oxide and prostaglandin E(2) production in murine
      macrophage RAW 264.7 cells.
AB  - Aberrantly activated macrophages, which overproduce inflammatory mediators, are
      involved in the pathogenesis of many inflammatory diseases. We analyzed the anti
      inflammatory activity of lansoprazole (LPZ), a typical proton pump (P-ATPase)
      inhibitor, on RAW264.7 murine macrophages. Treatment of lipopolysaccharide (LPS)
      stimulated RAW264.7 cells with LPZ inhibited the production of nitric oxide (NO)
      and prostaglandin E(2) (PGE(2)). Since P-ATPase expression was not observed in
      RAW264.7 cells, the anti-inflammatory effect of LPZ was independent of ATPase. In
      contrast, diphenylene iodonium (DPI), an inhibitor of nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase, decreased NO but not PGE(2) levels. LPZ
      suppressed the LPS-stimulated production by RAW264.7 cells of reactive oxygen
      species (ROS), which plays an important role in inflammatory responses. ROS
      elevation in these cells was associated with NO but not PGE(2) production,
      suggesting that LPZ inhibits NO production by suppressing NADPH oxidase activity.
      These findings suggest that LPZ may be useful in the treatment of many
      inflammatory diseases associated with activated macrophages.

PMID- 22134426
TI  - Xigris is withdrawn from the market. A 10 year odyssey.

PMID- 22134427
TI  - Lung recruitment maneuvers during acute respiratory distress syndrome: open up
      but not push-up the lung!

PMID- 22134428
TI  - Tracheostomy in ICU patients: question of timing is question of indication.

PMID- 22134429
TI  - Max Harry Weil, a world leading clinician, educator and scientist in the field of
      critical care. An Italian tribute.

PMID- 22134431
TI  - Down-regulation of P-glycoprotein expression contributes to an increase in
      Danshensu accumulation in the cerebral ischemia/reperfusion brain.
AB  - P-glycoprotein (P-gp) plays a key role in the distribution and elimination of
      many clinically important therapeutic substances. P-gp inhibition is capable of
      increasing the concentration of various drugs in the brain. Danshensu is a main
      hydrophilic constituent of Salvia miltiorrhiza Bunge which is used traditionally
      to treat cerebrovascular diseases. In the present study, the effects of cerebral
      ischemia/reperfusion on the transport of Danshensu in the brain were observed by
      assaying the concentration at 15, 30 and 60 min after cerebral
      ischemia/reperfusion in the brain of rats. Furthermore, the expression of P-gp in
      the brain was also measured. Results showed that Danshensu concentrations in the
      ischemic hemisphere significantly increased compared to those in the non-ischemic
      hemisphere and the brain of the sham group. P-gp expression was inhibited by
      cerebral ischemia/reperfusion to some extent, and down-regulated much more by
      Danshensu treatment. The findings indicate that the down-regulation of P-gp
      expression induced by both cerebral ischemia/reperfusion and Danshensu treatment
      contributes to the increase of Danshensu accumulation in the brain.

PMID- 22134432
TI  - Most probable number quantification of hypophosphite and phosphite oxidizing
      bacteria in natural aquatic and terrestrial environments.
AB  - Concentrations of hypophosphite and phosphite oxidizing bacteria were found to be
      high, relative to bacterial concentrations growing on phosphate, in sediment and
      soil during winter and summer seasons from 12 common terrestrial and aquatic
      sites using a most probable number method. The percent of total culturable
      bacterial concentrations that could use these reduced phosphorus compounds as a
      sole source of phosphorus were as follows: hypophosphite, 7-100%; phosphite, 10
      67%; aminoethylphosphonate, 34-270%. The average MPN/g (+/-SEM) was as follows:
      phosphate, 6.19 * 10(6) (+/-2.40 * 10(6)); hypophosphite, 2.61 * 10(6) (+/-1.35 *
      10(6)) phosphite, 1.91 * 10(6) (+/-1.02 * 10(6)); aminoethylphosphonate, 3.90 *
      10(6) (+/- 1.95 * 10(6)). Relatively high concentrations of reduced phosphorus
      oxidizing bacteria were found in both pristine sites and sites with urban and
      agricultural disturbance. Concentrations of reduced phosphorus oxidizing bacteria
      in anoxic sediments and soil were equivalent. Our data indicate that reduced
      phosphorus oxidizing bacteria are abundant in the environment and provide strong
      evidence for the importance of bacterial P oxidation in nature.

PMID- 22134433
TI  - Hepatitis B Vaccine in national immunization schedule: a preventive step in
      India.
AB  - Hepatitis B is a disease of the liver caused by Hepatitis B virus (HBV)
      infection. HBV is transmitted through contact with infected blood or body fluids,
      unprotected sexual intercourse and the perinatal route but not through casual
      contact. About two billion people worldwide have been infected with the virus, an
      estimated 360 million live with chronic infection, and at least 600,000 people
      die annually from acute or chronic consequences of Hepatitis B, such that
      Hepatitis B is a major public health problem worldwide. HBV is 50 to 100 times
      more infectious than HIV. It has been estimated that, of the 25 million infants
      born every year in India, over one million run the lifetime risk of developing
      chronic HBV infection. Every year over 100,000 Indians die due to illnesses
      related to HBV infection. Following the launch of the Global Alliance for
      Vaccines and Immunization (GAVI) to intensify National Immunization Programs
      (NIPs) in developing countries worldwide. World Health Organization (WHO)
      recommends that Hepatitis B vaccine should be given to all infants. Several cost
      effectiveness analyses of inclusion of Hepatitis B vaccine in India's NIP have
      been performed. These indicate that universal childhood Hepatitis B immunization
      in India will be highly cost-effective. The Government of India is also
      supporting planned state programs for introducing new vaccines as part of routine
      immunization. The current immunization schedule for hepatitis B vaccine includes
      a dose given as early as possible after birth, preferably within 24 hours for all
      institutional deliveries because the birth dose of Hepatitis B vaccine is
      effective in preventing perinatal transmission of Hepatitis B. Irrespective of
      the birth dose, 3 doses are to be given at 6, 10, 14 weeks at the same time as
      DPT and OPV.

PMID- 22134434
TI  - Long-term results of neurectomy in the treatment of Morton's neuroma: more than
      10 years' follow-up.
AB  - PURPOSE: The objective of this retrospective study was to evaluate the long-term
      follow-up results of neurectomy clinical outcomes and complications in the
      treatment of Morton's neuroma. MATERIALS AND METHODS: A total of 19 patients (19
      different feet) were treated for Morton's neuroma by excision of the interdigital
      nerve at our institute between May 1997 and May 1999. Thirteen (13 feet) of them
      were followed up. The 13 patients were female and had an average age of 43 years
      (range 34-54 years) at the time of the operation. The patients were followed-up
      for a mean of 10.5 years (range 10.0-12.2 years) and scored using the American
      Orthopaedic Foot & Ankle Society (AOFAS) forefoot scoring system and Visual
      Analogue Scale (VAS) score. Subjective satisfaction was evaluated at the final
      follow-up. RESULTS: Eight patients scored more than 90 on the AOFAS forefoot
      scoring system. The VAS score was improved in all patients. The mean preoperative
      VAS score was 8.6 +/- 0.8 cm (7-10) and the mean follow-up VAS score was 2.4 +/-
      1.8cm (0-6), which indicated no significant difference (P > .05). The final
      follow-up satisfaction results indicated that 4 patients were completely
      satisfied with the operation, 4 were satisfied with minor reservations, 5 were
      satisfied with major reservations, and no patient was unsatisfied. Neurectomy to
      treat Morton's neuroma had a good satisfaction rate (61%). Eleven of the patients
      complained of numbness on the plantar aspect of the foot adjacent to the
      interspace, and 2 of these 11 patients complained of disability induced by severe
      numbness. There was a complaint of residual pain by 1 patient. There were no skin
      problems on the operation lesions. CONCLUSION: The long-term results of
      neurectomy clinical outcomes in Morton's neuroma are slightly worse than the
      short- and mid-term results. LEVELS OF EVIDENCE: Therapeutic, Level IV,
      Retrospective case series.

PMID- 22134435
TI  - Hallux varus.

PMID- 22134436
TI  - The relationship between knee arthroplasty and foot loading.
AB  - Surgeons have questioned whether foot deformity applies abnormal loading on a
      knee implant. A total of 24 patients with mild knee deformity underwent a static
      recording of foot loading prior to and at 3 months following knee replacement. Of
      these patients, 13 had a preoperative varus deformity. The recorded postoperative
      to preoperative loading in all 6 geographic sites was decreased by an average of
      10%. The largest changes were observed in the hallux and lesser toe masks,
      whereas the postoperative to preoperative foot pressure ratio in the metatarsal
      head (lateral and medial), heel, and midfoot masks was 0.94. This preliminary
      investigation reveals a minimal change in geographic foot loading following total
      knee arthroplasty in patients with mild knee deformity.

PMID- 22134437
TI  - Pigmented villonodular synovitis of the ankle: an anterior-posterior technique
      for excision.
AB  - Because of its high recurrence rate, complete excision with total synovectomy is
      crucial for diffuse pigmented villonodular synovitis (DPVNS). Regardless of
      location, surgical approach requires meticulous soft tissue management and full
      joint exposure to assure complete tumor excision. In the ankle, PVNS can be
      present in the medial and lateral gutters, as well as extend along the
      syndesmotic ligament, flexor and peroneal tendon sheaths, and adjacent joints
      (ie, subtalar and midtarsal joints). The authors describe an open, anterior
      posterior technique for excision of DPVNS lesions from the ankle joint with
      erosive lesions of the tibia and talus, as well as from the flexor hallucis
      longus and peroneal tendon sheaths. Whereas previously described dual-incision
      techniques have focused on posteromedial and posterolateral approaches to the
      ankle, the authors' posterior exposure, in particular, uses a midline skin
      incision and a longitudinal split of the Achilles tendon. This provides an
      excellent exposure and minimizes potential wound healing complications.

PMID- 22134438
TI  - Arthrodesis of the first metatarsal-phalangeal joint with flexible, ridged
      titanium intramedullary nails alone or supplemented with static staples and
      immediate weight bearing: a consecutive series of 148 procedures.
AB  - Myriad forms of fixation have been proposed for arthrodesis of the first
      metatarsal-phalangeal joint (MTPJ). However, nonunion of the arthrodesis site
      remains a common complication. The authors performed a retrospective review of
      all patients undergoing arthrodesis of the first MTPJ with flexible titanium
      intramedullary nails alone or supplemented with static staples followed by
      immediate protected weight bearing. Subjects were included if they had surgery
      performed only by one of us; not undergone bilateral surgery in the same setting;
      surgery for pathology of the first MTPJ other than rheumatoid arthritis; weight
      bearing preoperative radiographs; postoperative weight-bearing radiographs
      demonstrating presence or absence of union at the arthrodesis site; initiated
      weight bearing on the operative foot immediately postoperative in a protective
      shoe; and documentation of any complications. A total of 128 patients (148 feet)
      met inclusion criteria and were included. There were 110 (85.9%) females and 18
      (14.1%) males with a mean age +/- SD of 64 +/- 14.1 years. Indications included
      (a) 93 (62.8%) severe hallux valgus deformity, (b) 37 (25%) hallux rigidus, and
      (c) 18 (12.2%) failed first MTPJ surgeries. Ten different configurations where
      included based on the requirements needed to achieve a solid construct
      intraoperatively. There were a total of 9 (6.1%) complications consisting of 4
      (2.7%) asymptomatic nonunions, 4 (2.7%) hardware removals, and 1 (0.7%) loss of
      reduction requiring revision surgery. The incidence of nonunion with flexible
      titanium intramedullary nails alone or supplemented with static staples followed
      by immediate protected weight bearing for predominantly severe hallux valgus and
      hallux rigidus is lower than the historic mean for most other fixation
      techniques. However, there is still a need for methodologically sound prospective
      cohort studies that focus on the use of isolated arthrodesis of the first MTPJ
      for purely severe hallux valgus or hallux rigidus, and comparison of the
      technique presented here with other modern osteosynthesis techniques. Levels of
      Evidence : Therapeutic, Level IV.

PMID- 22134439
TI  - Closed total talar extrusion after ankle sprain.
AB  - Closed total talus dislocation from tibiotalar, subtalar, and talonavicular
      joints is a very rare injury. A 25-year-old young man, who had severe ankle
      distortion while walking down a flight of stairs, was brought to the emergency
      room complaining of a deformity and pain in his ankle joint. Roentgenographies
      revealed total talar body extrusion. The patient was treated urgently with open
      reduction in the authors' clinic. Tibialis posterior tendon might prevent closed
      reduction so open reduction with retraction of the tendon may be necessary.

PMID- 22134440
TI  - Surgical intervention in vascular trauma in children.
AB  - Vascular trauma is uncommon in children but may be complex. Arterial injury in
      children presents a challenge to the surgeon and may have long-term implications.
      Children have major advantage of a rich-collateral circulation but are still
      growing and developing. Decisions about when to operate remain an issue. METHODS:
      Patients (<13 years) with vascular injury requiring surgical intervention were
      retrospectively reviewed from a trauma database of 446 trauma patients admitted
      to the Tygerberg Children's Hospital. Demographic data, and factors influencing
      the outcome were studied, as well as different modalities of management. RESULTS:
      We reviewed a total of 20 children where surgical intervention for vascular
      trauma was required. Six resulted from penetrating injuries (two gunshots), ten
      followed blunt trauma (two popliteal extension injuries), one degloving injury,
      two presented later with arterio-venous fistulae. Haemorrhage from the wound in
      one haemophiliac patient made urgent surgery mandatory. One patient with a
      gunshot damage of the vertebral artery was successfully managed by radiological
      embolism (coils). Outcome was variable and long-term limb maldevelopment occurred
      in one patient. CONCLUSION: Vascular injuries may be difficult to manage in
      childhood due to their complexity. Growth and developmental considerations must
      be borne in mind during treatment.

PMID- 22134441
TI  - Bacterial dioxygenase- and monooxygenase-catalysed sulfoxidation of
      benzo[b]thiophenes.
AB  - Asymmetric heteroatom oxidation of benzo[b]thiophenes to yield the corresponding
      sulfoxides was catalysed by toluene dioxygenase (TDO), naphthalene dioxygenase
      (NDO) and styrene monooxygenase (SMO) enzymes present in P. putida mutant and E.
      coli recombinant whole cells. TDO-catalysed oxidation yielded the relatively
      unstable benzo[b]thiophene sulfoxide; its dimerization, followed by
      dehydrogenation, resulted in the isolation of stable tetracyclic sulfoxides as
      minor products with cis-dihydrodiols being the dominant metabolites. SMO mainly
      catalysed the formation of enantioenriched benzo[b]thiophene sulfoxide and 2
      methyl benzo[b]thiophene sulfoxides which racemized at ambient temperature. The
      barriers to pyramidal sulfur inversion of 2- and 3-methyl benzo[b]thiophene
      sulfoxide metabolites, obtained using TDO and NDO as biocatalysts, were found to
      be ca.: 25-27 kcal mol(-1). The absolute configurations of the benzo[b]thiophene
      sulfoxides were determined by ECD spectroscopy, X-ray crystallography and
      stereochemical correlation. A site-directed mutant E. coli strain containing an
      engineered form of NDO, was found to change the regioselectivity toward
      preferential oxidation of the thiophene ring rather than the benzene ring.

PMID- 22134442
TI  - Body image, sexual function and depression in Korean patients with breast cancer:
      modification by 5-HTT polymorphism.
AB  - BACKGROUND: Nearly 50% of women with breast cancer show depressive symptoms after
      diagnosis and treatment. The purpose of this study was to clarify how
      psychosocial factors (body image, sexuality, and social relationships) and
      genetic factors (functional polymorphism of the serotonin transporter-linked
      promoter region) influence depression. METHODS: The participants were categorized
      by DSM-IV diagnoses; scored according to their depressive symptoms, body image
      and social and sexual function (BIRS), self-esteem, and quality of life; and
      genotyped by functional polymorphism of the serotonin transporter promoter.
      RESULTS: Patients with depressive symptoms showed low self-esteem, poor body
      image, relationship problems, and low quality of life. Genotype frequencies did
      not differ between two groups categorized by the presence or absence of
      depressive symptoms. However, the patients with the short allele of the 5-HTTLPR
      had significantly higher HAM-D scores (F = 7.59, p = 0.047). CONCLUSION: The
      results suggest that psychosocial factors related to breast cancer treatment such
      as body image, self-esteem, and interpersonal relationship influence the
      development of depressive symptoms. The 5-HTTLPR may be associated with the
      severity of depressive symptoms rather than susceptibility to the development of
      depressive symptoms.

PMID- 22134443
TI  - Expanded carrier screening and the law of unintended consequences: from cystic
      fibrosis to fragile X.

PMID- 22134445
TI  - Posttraumatic stress disorder and war.

PMID- 22134446
TI  - Sur l'etat atrophique de la moelle epiniere dans le syphilis spinale chronique
      (The atrophic state of the spinal cord in chronic spinal syphilis). 1901.

PMID- 22134447
TI  - Neurosyphilis and the spinal cord: then and now.

PMID- 22134448
TI  - Suicidal ideation among National Guard troops deployed to Iraq: the association
      with postdeployment readjustment problems.
AB  - Despite well-documented postdeployment readjustment problems affecting veterans
      of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF), few studies have
      explored the possible relationship of readjustment stressors to the recent
      increase in military suicide. This study examined associations between suicidal
      ideation and postdeployment readjustment problems using cross-sectional
      population-based survey data from 1665 National Guard members who recently
      returned from Iraq. The findings suggested that readjustment problems are
      widespread, with 45% of veterans endorsing one or more financial or family
      problems 3 months postdeployment. After adjusting for mental health and combat
      exposure, veterans with the highest number of readjustment stressors were at 51/2
      times greater risk of suicidal ideation than those with no stressors. In a
      psychiatrically impaired subsample, the high stressor group experienced a
      fourfold risk of suicide ideation compared with those with no stressors. The
      findings argue for suicide prevention efforts that more directly target
      readjustment problems in returning OEF/OIF veterans.

PMID- 22134449
TI  - Rumination and avoidance as predictors of prolonged grief, depression, and
      posttraumatic stress in female widowed survivors of war.
AB  - This study examined independent contributions of rumination and experiential
      avoidance in predicting symptoms of psychological distress among female widowed
      survivors of war. A decade after the war in Kosovo, 100 widowed survivors of war
      completed measures of rumination, experiential avoidance, depression,
      posttraumatic stress, and prolonged grief. Results showed that both rumination
      and experiential avoidance significantly predicted the symptom severity of
      prolonged grief, depression, and posttraumatic stress. Furthermore, rumination
      accounted for additional variance above and beyond experiential avoidance and
      vice versa. Finally, the interaction of rumination and experiential avoidance did
      not provide significant explanatory power over and above the individual main
      effects. These findings suggest that rumination and experiential avoidance may be
      significant factors in understanding and treating psychological distress
      following exposure to potentially traumatic events and loss due to violence.

PMID- 22134450
TI  - Associations between traumatic events and suicidal behavior in South Africa.
AB  - Research conducted predominantly in the developed world suggests that there is an
      association between trauma exposure and suicidal behavior. However, there are
      limited data available investigating whether specific traumas are uniquely
      predictive of suicidal behavior or the extent to which traumatic events predict
      the progression from suicide ideation to plans and attempts. A national survey
      was conducted with 4351 adult South Africans between 2002 and 2004 as part of the
      World Health Organization World Mental Health Surveys. Data on trauma exposure
      and subsequent suicidal behavior were collected. Bivariate and multivariate
      survival models tested the relationship between the type and number of traumatic
      events and lifetime suicidal behavior. A range of traumatic events are associated
      with lifetime suicide ideation and attempt; however, after controlling for all
      traumatic events in a multivariate model, only sexual violence (odds ratio = 4.7;
      confidence interval, 2.3 to 9.4) and having witnessed violence (odds ratio = 1.8;
      confidence interval, 1.1 to 2.9) remained significant predictors of lifetime
      suicide attempts. The disaggregation of the associations between traumatic events
      and suicide attempts indicates that they are largely caused by traumatic events
      predicting suicide ideation rather than by the progression from suicide ideation
      to attempt. This article highlights the importance of traumatic life events in
      the occurrence of suicidal thoughts and behaviors and provides important
      information about the nature of this association. Future research is needed to
      better understand how and why such experiences increase the risk of suicidal
      outcomes.

PMID- 22134451
TI  - Lifetime traumatic experiences and posttraumatic stress disorder in the German
      population: results of a representative population survey.
AB  - Only a few European population-based studies on the epidemiology of posttraumatic
      stress disorder (PTSD) are available to date. This study aims to broaden the
      epidemiological knowledge of traumatic experiences (TEs), PTSD, and comorbid
      mental conditions in a representative German sample (N = 2510). The Composite
      International Diagnostic Interview list of traumatic events, the Posttraumatic
      Diagnostic Scale, and Patient Health Questionnaire (PHQ)-9 as well as PHQ-15 were
      used in this survey. Main results were low frequencies of TEs (24%) and PTSD
      (2.9%). Older participants (>60 years) reported significantly more TEs and more
      posttraumatic symptoms, whereas there was no significant difference in PTSD
      prevalence. A third of the subjects diagnosed with PTSD were found positive for
      depressive syndromes, and 27% were found positive for somatization syndrome. The
      results show that TEs and posttraumatic symptoms are frequent in senior citizens
      and thus have to be considered when treating older patients with mental health
      conditions.

PMID- 22134452
TI  - The influence of posttraumatic stress disorder numbing and hyperarousal symptom
      clusters in the prediction of physical health status in veterans with chronic
      tobacco dependence and posttraumatic stress disorder.
AB  - Smoking and PTSD are predictors of poor physical health status. This study
      examined the unique contribution of PTSD symptoms in the prediction of the SF-36
      physical health status subscales accounting for cigarette smoking, chronic
      medical conditions, alcohol and drug use disorders, and depression. This study
      examined baseline interview and self-report data from a national tobacco
      cessation randomized, controlled trial (Veterans Affairs Cooperative Study 519)
      that enrolled tobacco-dependent veterans with chronic PTSD (N = 943). A series of
      blockwise multiple regression analyses indicated that PTSD numbing and
      hyperarousal symptom clusters explained a significant proportion of the variance
      across all physical health domains except for the Physical Functioning subscale,
      which measures impairments in specific physical activities. Our findings further
      explain the impact of PTSD on health status by exploring the way PTSD symptom
      clusters predict self-perceptions of health, role limitations, pain, and
      vitality.

PMID- 22134453
TI  - Secondary traumatic stress in attorneys and their administrative support staff
      working with trauma-exposed clients.
AB  - Although secondary trauma has been assessed in various groups of mental health
      professionals, few studies, to date, have examined secondary trauma among
      attorneys exposed to clients' traumatic experiences. This study examined
      indicators of secondary trauma among attorneys (N = 238) and their administrative
      support staff (N = 109) in the Wisconsin State Public Defender Office. Attorney
      participants demonstrated significantly higher levels of posttraumatic stress
      disorder symptoms, depression, secondary traumatic stress, burnout, and
      functional impairment compared with the administrative support staff. This
      difference was mediated by attorneys' longer work hours and greater contact with
      clients who had experienced or had been directly involved with trauma. Sex, age,
      years on the job, office size, and personal history of trauma did not predict
      symptoms. These findings suggest a need to support attorneys experiencing these
      symptoms and to address high workloads as well as the intensity of contact with
      trauma-exposed clients.

PMID- 22134454
TI  - Pathological gambling and the structure of common mental disorders.
AB  - This study investigated a proposed three-factor model of common mental disorders
      in the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC; N
      = 43,093). It also evaluated the inclusion of pathological gambling (PG) in the
      three-factor model to determine whether PG loaded more strongly on a higher-order
      externalizing factor comprised of alcohol and drug dependence and antisocial
      personality disorder. The results indicated the three-factor model showed good
      fit to the NESARC data. PG loaded onto the externalizing factor for men and
      women, but in women, PG showed the best fit when it was allowed to load on the
      externalizing factor as well as a lower-order internalizing factor of anxious
      misery composed primarily of mood disorders. Findings emphasize the need to
      investigate the differences in the nature of PG behavior between men and women.

PMID- 22134455
TI  - Cognitive vulnerability in moderate, mild, and low seasonality.
AB  - This study examined the association between cognitive vulnerability factors and
      seasonality. Students (N = 88), classified based on the Seasonal Pattern
      Assessment Questionnaire as experiencing moderate (n = 26) or mild (n = 32)
      seasonality, and nondepressed, low-seasonality controls (n = 30) completed
      explicit (i.e., dysfunctional attitudes, automatic negative thoughts, seasonal
      attitudes, and rumination) and implicit (i.e., implicit associations test)
      measures of cognitive vulnerability at one winter and one nonwinter assessment.
      Relative to low- and mild-seasonality participants, moderate-seasonality
      participants endorsed more automatic thoughts and rumination in winter and more
      dysfunctional attitudes across both seasons. Moderate- and mild-seasonality
      participants endorsed more maladaptive seasonal attitudes than did low
      seasonality participants. All groups demonstrated increased dysfunctional
      attitudes, automatic thoughts, and rumination and stronger implicit associations
      about light and dark during the winter. The findings support a possible cognitive
      mechanism of winter depression onset and/or maintenance unique to individuals
      with moderate, as opposed to mild, seasonality.

PMID- 22134456
TI  - Emotional priming with facial exposures in euthymic patients with bipolar
      disorder.
AB  - People with bipolar disorder have abnormal emotional processing. We investigated
      the automatic and controlled emotional processing via a priming paradigm with
      subliminal and supraliminal facial exposure. We compared 20 euthymic bipolar
      patients and 20 healthy subjects on their performance in subliminal and
      supraliminal tasks. Priming tasks consisted of three different primes according
      to facial emotions (happy, sad, and neutral) followed by a neutral face as a
      target stimulus. The prime stimuli were presented subliminally (17 msec) or
      supraliminally (1000 msec). In subliminal tasks, both patients and controls
      judged the neutral target face as significantly more unpleasant (negative
      judgment shift) when presented with negative emotion primes compared with
      positive primes. In supraliminal tasks, bipolar subjects showed significant
      negative judgment shift, whereas healthy subjects did not. There was a
      significant group * emotion interaction for the judgment rate in supraliminal
      tasks. Our finding of persistent affective priming even at conscious awareness
      may suggest that bipolar patients have impaired cognitive control on emotional
      processing rather than automatically spreading activation of emotion.

PMID- 22134457
TI  - Effectiveness of the cognitive differentiation program of the integrated
      psychological therapy: group versus individual treatment.
AB  - The aim of the current pilot study was to compare two strategies in the
      application of the cognitive differentiation program of Integrated Psychological
      Therapy for people with schizophrenia. Twenty-six outpatients were randomly
      assigned to the application of the program in group sessions (CDg), or to its
      application in individualized sessions (CDi). The program provides cognitive
      exercises to promote better performance in cognition, and both groups of
      participants completed the same number of exercises following the same number of
      sessions per week. Outcomes were assessed on neuropsychological measures of
      attention, executive functioning and everyday memory, and everyday functioning.
      Effect sizes showed the absence of effects in everyday memory and social
      functioning, higher improvements in the CDi group in attention, and a higher
      improvement in the CDg condition in executive functioning. The results suggest
      that the program application model could be individualized, depending on patient
      specific cognitive deficits.

PMID- 22134458
TI  - Reliability of adherence and competence assessment in psychoeducational
      treatment: influence of clinical experience.
AB  - For the evaluation of therapist competence in psychotherapeutic treatment, only
      highly experienced judges (experts) were found to be adequate, whereas therapist
      adherence could be assessed by nonexperts. Using experts implies high costs for
      the rating process. Therefore, an interesting question is whether experts are
      also necessary for the assessment of therapist adherence and competence in
      psychoeducational treatment. To test this, four judges evaluated therapist
      adherence and competence in 30 randomly selected videotaped sessions of
      manualized psychoeducation for recurrent depression. Two judges exhibited high
      clinical experience (experts) while two judges did not (novices). We could
      demonstrate that the novices were also able to evaluate therapists' adherence and
      competence in psychoeducative treatment with high reliability. Moreover, expert
      judgments were not more reliable than novice judgments. Adherence and competence
      ratings of experts and novices showed high concordance. These results carry
      implications in terms of reducing costs associated with the judgment process.

PMID- 22134459
TI  - Risperidone and lorazepam concomitant use in clonazepam refractory catatonia: a
      case report.
AB  - The DSM-IV recognizes catatonia as a subtype of schizophrenia characterized by at
      least two of the following: motor immobility, excessive motor activity not
      influenced by external stimuli, and peculiarities of voluntary movement.
      Catatonia may also occur secondary to mania, depression, or a general medical
      condition including encephalitis, focal neurological lesions, metabolic
      disturbances, and drug intoxications and withdrawals. Benzodiazepines remain the
      first line of treatment; up to 80% of patients respond promptly to Lorazepam
      challenge; failure to respond to lorazepam may be followed by electroconvulsive
      therapy. Atypical antipsychotics may be a new alternative in the treatment of
      catatonia. Successful reduction of the catatonic symptoms has been demonstrated
      with atypical antipsychotics. A possible mechanism of action for the efficacy of
      this class of drugs involves the antagonism of the 5-HT2A receptor. We are now
      reporting a case of treatment response to risperidone in a patient with chronic
      catatonia resistant to benzodiazepines.

PMID- 22134460
TI  - Case report on the management of depression in schizoaffective disorder, bipolar
      type focusing on lithium levels and measurement-based care.
AB  - There is little evidence supporting the management of depression in
      schizoaffective disorder, bipolar type. Managing bipolar depression can be a
      daunting task for clinicians. Most bipolar patients spend 80% of their time in
      the depressive phase of illness. In contrast with full-blown mania, patients and
      family frequently fail to recognize bipolar depression, which may interfere with
      early diagnosis and treatment. With only a few medications approved for bipolar
      depression, treatment becomes very challenging. There is evidence to support that
      schizoaffective depression has a worse outcome than psychotic depression and
      nonpsychotic depression. We report a patient with schizoaffective disorder,
      bipolar type with severe depression who responded to an adequate level of lithium
      and subsequently, on a combination of lithium and quetiapine. Finally, we
      emphasize the importance of measurement-based care. To our knowledge, this is the
      first case report focusing on the management of depression in schizoaffective
      disorder, bipolar type.

PMID- 22134463
TI  - On the interaction of Mg with the (111) and (110) surfaces of ceria.
AB  - The catalytic activity of cerium dioxide can be modified by deposition of
      alkaline earth oxide layers or nanoparticles or by substitutional doping of metal
      cations at the Ce site in ceria. In order to understand the effect of Mg oxide
      deposition and doping, a combination of experiment and first principles
      simulations is a powerful tool. In this paper, we examine the interaction of Mg
      with the ceria (111) surface using both angle resolved X-ray (ARXPS) and resonant
      (RPES) photoelectron spectroscopy measurements and density functional theory
      (DFT) corrected for on-site Coulomb interactions (DFT + U). With DFT + U, we also
      examine the interaction of Mg with the ceria (110) surface. The experiments show
      that upon deposition of Mg, Ce ions are reduced to Ce(3+), while Mg is oxidised.
      When Mg is incorporated into ceria, no reduced Ce(3+) ions are found and oxygen
      vacancies are present. The DFT + U simulations show that each Mg that is
      introduced leads to formation of two reduced Ce(3+) ions. When Mg is incorporated
      at a Ce site in the (111) surface, one oxygen vacancy is formed for each Mg to
      compensate the different valencies, so that all Ce ions are oxidised. The
      behaviour of Mg upon interaction with the (110) surface is the same as with the
      (111) surface. The combined results provide a basis for deeper insights into the
      catalytic behaviour of ceria-based mixed oxide catalysts.

PMID- 22134466
TI  - Tunable nanostructures as photothermal theranostic agents.
AB  - The theranostic potential of several nanostructures has been discussed in the
      context of photothermal therapies and imaging. In the last several decades, the
      burden of cancer has grown rapidly, making the need for new theranostic
      approaches vital. Lasers have emerged as promising tools in cancer treatment,
      especially with the advent of photothermal therapies wherein light absorbing dyes
      or plasmonic gold nanoparticles are used to generate heat and achieve tumor
      damage. Recently, photoabsorbing nanostructures have materialized that can be
      employed in conjunction with lasers in the near-infrared region in order to
      enhance both imaging and photothermal effects. The incorporation of tunable
      nanostructures has resulted in improved specificity in cancer treatment. Silica
      cored gold nanoshells and gold nanorods currently serve as the chief plasmonic
      structures for photothermal therapy. Although gold nanorods and silica-cored gold
      nanoshells have shown promise as therapeutic agents, over the past few years new
      nanostructures have emerged that offer comparable and even superior theranostic
      properties. In the present review, several theranostic agents and their impact on
      the development of more effective photothermal therapies for the treatment of
      cancer are discussed. These agents include hollow gold nanoshells, gold gold
      sulfide nanoparticles, gold nanocages, carbon and titanium nanotubes,
      photothermal-based nanobubbles, polymeric nanoparticles and copper-based
      nanocrystals.

PMID- 22134467
TI  - Effects of moveable platform training in preventing slip-induced falls in older
      adults.
AB  - Identifying effective interventions is vital in preventing slip-induced fall
      accidents in older adults. The purpose of the current study was to evaluate the
      efficacy of moveable platform training in improving recovery reactions and
      reducing fall frequency in older adults. Twenty-four older adults were recruited
      and randomly assigned to two groups (training and control). Both groups underwent
      three sessions including baseline slip, training, and transfer of training on a
      slippery surface. Both groups experienced two slips on a slippery surface, one
      during the baseline and the other (after 2 weeks) during the transfer of training
      session. In the training session, the training group underwent twelve simulated
      slips using a moveable platform while the control group performed normal walking
      trials. Kinematic, kinetic, and EMG data were collected during all the sessions.
      Results indicated a reduced incidence of falls in the training group during the
      transfer of training trial as compared to the control group. The training group
      was able to transfer proactive and reactive control strategies learned during
      training to the second slip trial. The proactive adjustments include increased
      center-of-mass velocity and transitional acceleration after training. Reactive
      adjustments include reduction in muscle onset and time to peak activations of
      knee flexors and ankle plantar flexors, reduced ankle and knee coactivation,
      reduced slip displacement, and reduced time to peak knee flexion, trunk flexion,
      and hip flexion velocities. In general, the results indicated a beneficial effect
      of perturbation training in reducing slip severity and recovery kinematics in
      healthy older adults.

PMID- 22134469
TI  - Physical exercise in young patients with congenital heart disease.
AB  - The aim of this paper is to clarify two important aspects about patients affected
      by congenital heart disease. Their functional status plays a dominant role in the
      definition of quality of life related to health status, because of its
      implication in working and recreational activities. In the first part, we explain
      their cardiovascular adaptation on exercise, based on pathology (Tetralogy of
      Fallot, transposition of great arteries, univentricular heart). In the second
      part, we explain the risk of sudden death from congenital heart disease due to
      exercise, because of electrical cardiac instability and/or the structural
      abnormalities of the cardiovascular parietal walls.

PMID- 22134468
TI  - In high risk hypertensive subjects with incidental and unilateral renal artery
      stenosis percutaneous revascularization with stent improves blood pressure
      control but not glomerular filtration rate.
AB  - AIM: In high-risk hypertensive subjects (HTs) with incidental unilateral renal
      artery stenosis (RAS), the effectiveness of percutaneous revascularization with
      stent (PR-STENT) on blood pressure (BP) and glomerular filtration rate (GFR) is
      not established. METHODS: Eighteen HTs aged 65.7 +/- 9.2 years with
      angiographically diagnosed unilateral RAS (>= 60%) were randomized to receive PR
      STENT (N=9) or to NO-STENT (N=9). BP (mercury sphygmomanometer) and GFR (99mTc
      DTPA clearances during renal scintigraphy) were evaluated yearly for three years.
      Echo-Doppler of renal arteries was performed to verify the anatomic patency and
      flow velocities of the reperfused artery. Analysis of variance compared BP and
      GFR values changes from baseline to the follow-up; differences for continuous
      variables were evaluated between groups with the Tukey's post hoc test after
      adjustment for age, change of BP between baseline and at the follow-up, GFR and
      body mass index (BMI). RESULTS: Baseline systolic BP and GFR values were not
      different between groups. The significantly greater GFR increase observed in PR
      STENT than in NO-STENT at univariate analysis at the end of follow-up (62.5 +/-
      19.2 vs. 42.24 +/- 17.6, P<0.02) disappeared after adjustment for confounding
      factors. However, systolic BP remained significantly lower in PR-STENT than in NO
      STENT (140.1 +/- 4.6 vs. 170.0 +/- 8.3, P<0.0001) also after adjustment for age,
      GFR and BMI. CONCLUSION: PR-STENT reduces systolic BP without improving GFR. Due
      to the strong association between high BP and renal damage, this study raises the
      question on whether PR-STENT should be performed in all HTs with unilateral and
      incidental RAS.

PMID- 22134470
TI  - Management of left ventricular outflow obstruction due to hypertrophic
      cardiomyopathy. Role of multimodality echocardiographic techniques.
AB  - Hypertrophic cardiomyopathy is a diverse condition, encompassing a wide spectrum
      of clinical manifestations. Left ventricular outflow obstruction occurs in a
      proportion of patients, and is amenable to a variety of management strategies.
      Echocardiography plays a crucial role in the diagnosis of hypertrophic
      cardiomyopathy, and in the assessment of left ventricular outflow obstruction, as
      well the selection of appropriate therapy. In particular echocardiography is
      crucial in the selection, intraoperative monitoring and follow-up of patients
      suitable for alcohol septal ablation therapy. This article outlines the role of
      echocardiography in the assessment and management of left ventricular outflow
      obstruction in these patients.

PMID- 22134471
TI  - Carotid plaque characterisation by IVUS-VH during carotid stenting: the "eyes
      wide shut" between plaque morphology and symptoms.
AB  - Stroke is the third most common cause of death in North America and ever year
      approximately 700,000 new strokes are reported in the United States. Seventy-five
      percent of these occur in the distribution of the carotid arteries. Among strokes
      of a thromboembolic etiology, carotid occlusive disease is the most common cause.
      As many as 150,300 stroke-related fatalities are documented annually, with a
      total cost for the health-care system of approximately $ 18 billion per year.
      This review will focus on the different pathomorphologic aspects of carotid
      plaque, outlining the similarities and differences with the coronary plaque, with
      particular attention on how intravascular imaging may contribute to a better
      stratification of the patient treatment.

PMID- 22134472
TI  - Patent foramen ovale-mania: an unusual case of misdiagnosis.
AB  - Patent foramen ovale (PFO) is rapidly becoming in Europe, more than in the USA, a
      matter of over-diagnosis and over-treatment. A migrainous 34-year-old female with
      episodic hypostenia and even paralysis of the left arm was referred to a
      peripheral hospital for a complete neurological work-up. Being the Doppler
      ultrasound of carotid and vertebral arteries negative and angio-magnetic
      resonance imaging (MRI) positive for multiple white-matter lesions. A
      transthoracic echocardiography revealed a possible shunt through a patent foramen
      ovale with a right-to-left shunt and a mild buldging of interatrial septum, but
      the patient did not tolerate a further attempt of transesophageal
      echocardiography to confirm the diagnosis. Coagulation screening essay
      demonstrated a moderate hyperhomocisteinemia. In the hypothesis of embolic PFO
      mediated by a moderate prothrombotic state caused by hyperhomocisteinemia, the
      patient was referred to our attention for an attempt of PFO closure but on
      intracardiac echocardiography normal fossa ovalis without any shunt was revealed.
      One year later, during the follow-up, the patient became severely symptomatic for
      left arm hypostenia and parhestesia, both at rest and during efforts. Thus, the
      patient was submitted to a thoracic and upper limbs angio-MRI in order to exclude
      disease of the main arteries causing functional impotence. The MRI demonstrated
      thoracic outlet syndrome of both arms, more severe in the left arm with
      functional occlusion of the subclavian vein with abduction of the arm and
      possible cloth image at the subclavian vein next to the joint. The patient was
      referred to the thoracic surgeon for surgical repair.

PMID- 22134473
TI  - A fibrous ring and a subaortic fibrous process conforming a tunnel obstruction in
      patient with recurrent pulmonary edema.

PMID- 22134474
TI  - Examining the effects of former cannabis use on cerebellum-dependent eyeblink
      conditioning in humans.
AB  - RATIONALE: Previous work in humans has shown that chronic cannabis users exhibit
      disruptions in classical eyeblink conditioning (EBC), a form of associative
      learning that is known to be dependent on the cerebellum. Based upon previous
      work in animals, it was hypothesized that these learning deficits were related to
      cannabinoid receptor (CB1R) downregulation. However, it remains unclear whether
      there is a recovery of cerebellum-dependent learning after the cessation of
      cannabis use. METHODS: Therefore, former cannabis users (n=10), current cannabis
      users (n=10), and cannabis-naive controls (n=10), all free of DSM-IV Axis-I or 
      II disorders, were evaluated. A standard delay EBC procedure was utilized in
      which paired presentations of a conditioned stimulus (CS; e.g., tone) and a co
      terminating unconditioned stimulus (US; e.g., ocular airpuff) were administered,
      thus eliciting a conditioned eyeblink response (CR). The primary dependent
      measures were percentage of CRs and CR latency across conditioning blocks.
      RESULTS: Similar to prior studies, current cannabis users exhibited marked
      impairments in both the acquisition and timing of CRs compared to controls.
      Although former cannabis users showed intact CR acquisition compared to controls,
      they exhibited significantly impaired (shorter) CR latencies. In both cannabis
      groups, UR amplitude did not differ from controls, indicating normal US
      processing. CONCLUSIONS: These data suggest that a recovery of function has
      occurred for the learning of the CS-US association, while the accurate timing of
      the CR shows lasting impairments. Taken together, these results suggest that
      heavy cannabis use can disrupt timing-related synaptic plasticity within the
      cerebellum, even after the cessation of cannabis use.

PMID- 22134475
TI  - Reliance on habits at the expense of goal-directed control following dopamine
      precursor depletion.
AB  - RATIONALE: Dopamine is well known to play an important role in learning and
      motivation. Recent animal studies have implicated dopamine in the reinforcement
      of stimulus-response habits, as well as in flexible, goal-directed action.
      However, the role of dopamine in human action control is still not well
      understood. OBJECTIVES: We present the first investigation of the effect of
      reducing dopamine function in healthy volunteers on the balance between habitual
      and goal-directed action control. METHODS: The dietary intervention of acute
      dietary phenylalanine and tyrosine depletion (APTD) was adopted to study the
      effects of reduced global dopamine function on action control. Participants were
      randomly assigned to either the APTD or placebo group (ns = 14) to allow for a
      between-subjects comparison of performance on a novel three-stage experimental
      paradigm. In the initial learning phase, participants learned to respond to
      different stimuli in order to gain rewarding outcomes. Subsequently, an outcome
      devaluation test and a slips-of-action test were conducted to assess whether
      participants were able to flexibly adjust their behaviour to changes in the
      desirability of the outcomes. RESULTS: APTD did not prevent stimulus-response
      learning, nor did we find evidence for impaired response-outcome learning in the
      subsequent outcome-devaluation test. However, when goal-directed and habitual
      systems competed for control in the slips-of-action test, APTD tipped the balance
      towards habitual control. These findings were restricted to female volunteers.
      CONCLUSIONS: We provide direct evidence that the balance between goal-directed
      and habitual control in humans is dopamine dependent. The results are discussed
      in light of gender differences in dopamine function and psychopathologies.

PMID- 22134476
TI  - Dissociable effects of monoamine reuptake inhibitors on distinct forms of
      impulsive behavior in rats.
AB  - RATIONALE: High levels of impulsivity are a core symptom of psychiatric disorders
      such as ADHD, mania, personality disorders and drug addiction. The effectiveness
      of drugs targeting dopamine (DA), noradrenaline (NA) and/or serotonin (5-HT) in
      the treatment of impulse control disorders emphasizes the role of monoaminergic
      neurotransmission in impulsivity. However, impulsive behavior is behaviorally and
      neurally heterogeneous, and several caveats remain in our understanding of the
      role of monoamines in impulse control. OBJECTIVES: This study aims to investigate
      the role of DA, NA and 5-HT in two main behavioral dimensions of impulsivity.
      METHODS: The effects of selective DA (GBR12909; 2.5-10 mg/kg), NA (atomoxetine;
      0.3-3.0 mg/kg) and 5-HT (citalopram; 0.3-3.0 mg/kg) reuptake inhibitors as well
      as amphetamine (0.25-1.0 mg/kg) were evaluated on impulsive action in the five
      choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed
      reward task (DRT). In the 5-CSRTT, neuropharmacological challenges were performed
      under baseline and long intertrial interval (ITI) conditions to enhance impulsive
      behavior in the task. RESULTS: Amphetamine and GBR12909 increased impulsive
      action and perseverative responding and decreased accuracy and response latency
      in the 5-CSRTT. Atomoxetine increased errors of omission and response latency
      under baseline conditions in the 5-CSRTT. Under a long ITI, atomoxetine also
      reduced premature and perseverative responding and increased accuracy. Citalopram
      improved impulse control in the 5-CSRTT. Amphetamine and GBR12909, but not
      citalopram or atomoxetine, reduced impulsive choice in the DRT. CONCLUSIONS:
      Elevation of DA neurotransmission increases impulsive action and reduces
      impulsive choice. Increasing NA or 5-HT neurotransmission reduces impulsive
      action.

PMID- 22134479
TI  - EGFR mutations predict a favorable outcome for malignant pleural effusion of lung
      adenocarcinoma with Tarceva therapy.
AB  - The aim of the present study was to evaluate the therapeutic effects and adverse
      reactions of Tarceva treatment for malignant pleural effusion (MPE) caused by
      metastatic lung adenocarcinomas. One hundred and twenty-eight patients who failed
      first-line chemotherapy drug treatment were divided into a mutation and a non
      mutation group according to the presence or absence of epidermal growth factor
      receptor (EGFR) mutations. Each patient received closed drainage combined with
      simple negative pressure suction after thoracoscopic talc poudrage pleurodesis
      and oral Tarceva treatment. Short-term and long-term clinical therapeutic effects
      of Tarceva were evaluated. The EGFR mutation rate in pleural metastatic tissues
      of lung adenocarcinoma acquired through video-assisted thoracoscopic surgery was
      higher compared to that in surgical resection specimens, plasma specimens and
      pleural effusion specimens compared to previously reported results. There were
      significant statistical differences in the average extubation time (p<0.01),
      drainage volume of pleural effusion (p<0.05), Karnofsky score and formation of
      encapsulated pleural effusion 4 weeks after surgery (p<0.05) between these two
      groups. The number of patients with mild pleural hypertrophy in the mutation
      group was significantly higher compared to the non-mutation group (p<0.01), while
      the number of patients with severe pleural hypertrophy was significantly reduced
      (p<0.05). There was significant statistical discrepancy between these two groups
      in terms of improvement of peripheral blood carcinoembryonic antigen and tissue
      polypeptide antigen after 4 weeks of therapy. The complete remission rate and the
      efficacy rate were higher in the mutation group compared to that in the non
      mutation group (p<0.05). There was a longer overall survival time after Tarceva
      treatment in patients with EGFR mutations than those without EGFR mutation. EGFR
      mutations predict a favorable outcome for malignant pleural effusion of lung
      adenocarcinoma with Tarceva therapy. Detection of EGFR mutations may determine
      the responsiveness of malignant pleural effusion to Tarceva treatment.

PMID- 22134477
TI  - Reversal learning as a measure of impulsive and compulsive behavior in
      addictions.
AB  - BACKGROUND: Our ability to measure the cognitive components of complex decision
      making across species has greatly facilitated our understanding of its
      neurobiological mechanisms. One task in particular, reversal learning, has proven
      valuable in assessing the inhibitory processes that are central to executive
      control. Reversal learning measures the ability to actively suppress reward
      related responding and to disengage from ongoing behavior, phenomena that are
      biologically and descriptively related to impulsivity and compulsivity.
      Consequently, reversal learning could index vulnerability for disorders
      characterized by impulsivity such as proclivity for initial substance abuse as
      well as the compulsive aspects of dependence. OBJECTIVE: Though we describe
      common variants and similar tasks, we pay particular attention to discrimination
      reversal learning, its supporting neural circuitry, neuropharmacology and genetic
      determinants. We also review the utility of this task in measuring impulsivity
      and compulsivity in addictions. METHODS: We restrict our review to instrumental,
      reward-related reversal learning studies as they are most germane to addiction.
      CONCLUSION: The research reviewed here suggests that discrimination reversal
      learning may be used as a diagnostic tool for investigating the neural mechanisms
      that mediate impulsive and compulsive aspects of pathological reward-seeking and 
      taking behaviors. Two interrelated mechanisms are posited for the
      neuroadaptations in addiction that often translate to poor reversal learning:
      frontocorticostriatal circuitry dysregulation and poor dopamine (D2 receptor)
      modulation of this circuitry. These data suggest new approaches to targeting
      inhibitory control mechanisms in addictions.

PMID- 22134481
TI  - CDKN2A/B alterations impair prognosis in adult BCR-ABL1-positive acute
      lymphoblastic leukemia patients.
AB  - PURPOSE: The 9p21 locus, encoding three important tumor suppressors (p16/CDKN2A,
      p14/ARF, and p15/CDKN2B), is a major target of inactivation in the pathogenesis
      of many human tumors. PATIENTS AND METHODS: To explore, at high resolution, the
      frequency and size of alterations affecting this locus in adult BCR-ABL1-positive
      acute lymphoblastic leukemia (ALL) and to investigate their prognostic value, 112
      patients (101 de novo and 11 relapsed cases) were analyzed by genome-wide single
      nucleotide polymorphism arrays and gene candidate deep exon sequencing. Paired
      diagnosis-relapse samples were further available and analyzed for 19 (19%) cases.
      RESULTS: CDKN2A/ARF and CDKN2B genomic alterations were identified in 29% and 25%
      of newly diagnosed patients, respectively. Deletions were monoallelic in 72% of
      cases, and in 43% of them, the minimal overlapping region of the lost area
      spanned only the CDKN2A/B gene locus. An analysis conducted at relapse showed an
      increase in the detection rate of CDKN2A/ARF loss (47%) compared with the time of
      diagnosis (P = 0.06). Point mutations within the 9p21 locus were found at very
      low levels, with only a nonsynonymous substitution in the exon 2 of CDKN2A. Of
      note, deletions of CDKN2A/B were significantly associated with poor outcomes in
      terms of overall survival (P = 0.0206), disease free-survival (P = 0.0010), and
      cumulative incidence of relapse (P = 0.0014). CONCLUSIONS: Inactivation of the
      9p21 locus by genomic deletion is a frequent event in BCR-ABL1-positive ALL.
      Deletions are frequently acquired during leukemia progression and are a poor
      prognostic marker of long-term outcomes.

PMID- 22134478
TI  - Effect of fenfluramine on reinstatement of food seeking in female and male rats:
      implications for the predictive validity of the reinstatement model.
AB  - RATIONALE AND OBJECTIVES: Relapse to old unhealthy eating habits while dieting is
      often provoked by stress or acute exposure to palatable foods. We adapted a rat
      reinstatement model, which is used to study drug relapse, to study mechanisms of
      relapse to palatable food seeking induced by food-pellet priming (non-contingent
      exposure to a small amount of food pellets) or injections of yohimbine (an alpha
      2 adrenoceptor antagonist that causes stress-like responses in humans and non
      humans). Here, we assessed the predictive validity of the food reinstatement
      model by studying the effects of fenfluramine, a serotonin releaser with known
      anorectic effects, on reinstatement of food seeking. METHODS: We trained food
      restricted female and male rats to lever-press for 45-mg food pellets (3-h
      sessions) and first assessed the effect of fenfluramine (0.75, 1.5, and 3.0
      mg/kg, i.p.) on food-reinforced responding. Subsequently, we extinguished the
      food-reinforced responding and tested the effect of fenfluramine (1.5 and 3.0
      mg/kg) on reinstatement of food seeking induced by yohimbine injections (2 mg/kg,
      i.p.) or pellet priming (four non-contingent pellets). RESULTS: Fenfluramine
      decreased yohimbine- and pellet-priming-induced reinstatement. As expected,
      fenfluramine also decreased food-reinforced responding, but a control condition
      in which we assessed fenfluramine's effect on high-rate operant responding
      indicated that the drug's effect on reinstatement was not due to performance
      deficits. CONCLUSIONS: The present data support the predictive validity of the
      food reinstatement model and suggest that this model could be used to identify
      medications for prevention of relapse induced by stress or acute exposure to
      palatable food during dietary treatments.

PMID- 22134484
TI  - A quantum chemical investigation of the electronic structure of thionine.
AB  - We have examined the electronic and molecular structure of 3,7
      diaminophenothiazin-5-ium dye (thionine) in the electronic ground state and in
      the lowest excited states. The electronic structure was calculated using a
      combination of density functional theory and multi-reference configuration
      interaction (DFT/MRCI). Equilibrium geometries were optimized employing (time
      dependent) density functional theory (B3LYP functional) combined with the TZVP
      basis set. Solvent effects were estimated using the COSMO model and micro
      hydration with up to five explicit water molecules. Our calculated electronic
      energies are in good agreement with experimental data. We find the lowest excited
      singlet and triplet states at the ground state geometry to be of pi->pi* (S(1),
      S(2), T(1), T(2)) and n->pi* (S(3), T(3)) character. This order changes when the
      molecular structure in the electronically excited states is relaxed. Geometry
      relaxation has almost no effect on the energy of the S(1) and T(1) states (~0.02
      eV). The relaxation effects on the energies of S(2) and T(2) are moderate (0.14
      0.20 eV). The very small emission energy results in a very low fluorescence rate.
      While we were not able to locate the energetic minimum of the S(3) state, we
      found a non-planar minimum for the T(3) state with an energy which is very close
      to the energy of the S(1) minimum in the gas phase (0.04 eV above). When
      hydration effects are taken into account, the n->pi* states S(3) and T(3) are
      strongly blueshifted (0.33 and 0.46 eV), while the pi->pi* states are only
      slightly affected (<0.06 eV).

PMID- 22134483
TI  - Evaluation of laparoscopic versus open colorectal surgery in elderly patients
      more than 70 years old: an evaluation of 727 patients.
AB  - BACKGROUND: With longer life expectancy, surgeons can expect to operate on older
      patients. Laparoscopic colorectal (LC) surgery has been demonstrated to be
      superior to open surgery. Controversy persists, however, regarding benefits of LC
      in the elderly due to increase in operative time. The aim of our study was to
      compare short-term outcomes of LC versus open colorectal (OC) surgery in elderly
      patients. MATERIALS AND METHODS: Patients >=70 years old that underwent elective
      LC between 2005 and 2008 were compared with controls who underwent OC. Data was
      extracted from a prospectively collected database. RESULTS: Seven hundred and
      twenty-seven patients underwent colorectal resection in this study period (LC n =
      225, OC n = 502). The laparoscopic arm was characterised by shorter incisions (LC
      6.0 cm vs. OC 12.0 cm, p < 0.001) but longer operating times (LC 125 min vs. OC
      85 min, p < 0.001). Median use of narcotics and length of stay were significantly
      shorter in the laparoscopic group (LC 2 days vs. OC 3 days, p < 0.001 and LC 6
      days vs. OC 7 days, p < 0.001, respectively). There was no significant difference
      in median recovery of bowel function (LC 4 days vs. OC 4 days, p = 0.14) and post
      operative morbidity (p = 0.725). Thirty-day mortality was significantly lower in
      the laparoscopic arm (LC 1.3% vs. OC 4.6%, p = 0.03) CONCLUSION: This is the
      largest series from a single institution comparing LC and OC in elderly patients.
      In our series, LC in elderly patients was safe and not associated with a higher
      morbidity. LC was also associated with less narcotic use and shorter length of
      stay.

PMID- 22134485
TI  - beta-Hairpin stabilization through an interstrand triazole bridge.
AB  - beta-Hairpin peptides were conformationally stabilized through a 1,4
      disubstituted 1,2,3-triazole interstrand linkage. A NMR conformational analysis
      revealed that the beta-hairpin content depends on the number and position of
      substituent methylene units of the 1,2,3-triazole ring. These results will allow
      the design of metabolically stable peptidomimetic analogs of bioactive beta
      hairpin peptides.

PMID- 22134486
TI  - Prevalence of heterotopic ossification after cervical total disc arthroplasty: a
      meta-analysis.
AB  - BACKGROUND: Heterotopic ossification (HO) is a well-known complication after
      total hip and knee arthroplasty. But limited studies have focused on prevalence
      of HO following cervical total disc arthroplasty (CTDA) and the published data
      show controversial results. OBJECTIVE: The purpose of this review is to
      investigate the prevalence of HO following CTDA by meta-analysis. METHODS: The
      literatures were collected from PubMed, Embase and Cochrane library by using
      keywords as ([disc or disk] and [arthroplasty or replacement]) and (HO or delayed
      fusion or spontaneous fusion). The original studies were eligible only if the
      prevalence of HO and of advanced HO (Grade 3-4 according to McAfee) were
      investigated. A meta-analysis was then performed on collected data. Statistical
      heterogeneity across the various trials was tested using Cochran's Q, statistic
      and in the case of heterogeneity a random effect model was used. Tests of
      publication bias and sensitivity analysis were also performed. RESULTS: Our data
      showed that the pooled prevalence of HO was 44.6% (95% confidence interval (CI),
      37.2-45.6%) 12 months after CTDA and 58.2% (95% CI, 29.7-86.8%) 24 months after
      CTDA, while the advanced HO was 11.1% (95% CI, 5.5-16.7%) and 16.7% (95% CI, 4.6
      28.9%), respectively. A significant heterogeneity was obtained. There was no
      publication bias and individual study had no significant effect on the pooled
      prevalence estimate. CONCLUSION: Higher prevalence of HO was observed following
      CTDA, although HO was reported to be unrelated to the clinical improvement. It
      suggests that cervical disc replacement should be performed cautiously before
      obtaining long-term supporting evidence. LEVEL OF EVIDENCE: Prognostic level III.

PMID- 22134487
TI  - Physical fitness, rather than self-reported physical activities, is more strongly
      associated with low back pain: evidence from a working population.
AB  - INTRODUCTION: Physical activity is suggested to be important for low back pain
      (LBP) but a major problem is the limited validity of the measurement of physical
      activities, which is usually based on questionnaires. Physical fitness can be
      viewed as a more objective measurement and our question was how physical activity
      based on self-reports and objective measured levels of physical fitness were
      associated with LBP. MATERIALS AND METHODS: We analyzed cross-sectional data of
      1,723 police employees. Physical activity was assessed by questionnaire (SQUASH)
      measuring type of activity, intensity, and time spent on these activities.
      Physical fitness was based on muscular dynamic endurance capacity and peak oxygen
      uptake (VO(2) peak). Severe LBP, interfering with functioning, was defined by
      pain ratings >= 4 on a scale of 0-10. RESULTS: Higher levels of physical fitness,
      both muscular and aerobic, were associated with less LBP (OR: 0.54; 95% CI: 0.34
      0.86, respectively, 0.59: 95%CI: 0.35-0.99). For self-reported physical activity,
      both a low and a high level of the total physical activity pattern were
      associated with an increase of LBP (OR: 1.52; 95%CI: 1.00-2.31, respectively,
      1.60; 95%CI: 1.05-2.44). CONCLUSION: These findings suggest that physical
      activity of an intensity that improves physical fitness may be important in the
      prevention of LBP.

PMID- 22134488
TI  - Stability, electronic and magnetic properties of embedded triangular graphene
      nanoflakes.
AB  - Stability, electronic and magnetic properties of triangular graphene nanoflakes
      embedded in graphane (graphane-embedded TGNFs) are investigated by density
      functional theory. It is found that the interface between the embedded TGNF and
      graphane is stable since the diffusion of H atoms from the graphane region to the
      embedded TGNF is energetically unfavorable with high energy barriers. The
      electronic and magnetic properties of the system completely depend on the
      embedded TGNF. The band gaps of graphane-embedded ATGNFs (armchair-edged TGNFs)
      arise due to the quantum confinement, while the special characteristics of
      nonbonding states of graphane-embedded ZTGNFs (zigzag-edged TGNFs) play an
      important role in their electronic properties. As the edge sizes increase, the
      differences of band gaps between graphane-embedded TGNFs and the isolated ones
      decrease. Furthermore, owing to the partially paired p(z) orbitals of edge C
      atoms, graphane-embedded ZTGNFs exhibit a ferrimagnetic ground state with size
      dependant total spin being consistent with Lieb's theorem. Our work provides a
      possible way to obtain TGNFs without physical cutting.

PMID- 22134489
TI  - Processing speed and neurodevelopment in adolescent-onset psychosis: cognitive
      slowing predicts social function.
AB  - Onset of psychosis may be associated with abnormal adolescent neurodevelopment.
      Here we examined the neurocognitive profile of first-episode, adolescent onset
      psychosis (AOP) as compared to typically developing adolescents, and asked
      whether neurocognitive performance varied differentially as a function of age in
      the cases compared with controls. A comprehensive neuropsychological battery was
      administered to 35 patients experiencing a first-episode of a DSM-IV psychotic
      disorder and to 31 matched controls. Clinicians also rated subjects' social and
      role functioning, both at the time of neuropsychological assessment and 1 year
      later. Although patients displayed a wide range of impairments relative to
      controls, their most pronounced deficits included verbal memory, sensorimotor
      dexterity and cognitive processing speed. Among these, only processing speed
      showed a significant group-by-age interaction, consistent with an aberrant
      developmental course among AOP patients. Processing speed also accounted for
      substantial variance in other areas of deficit, and predicted social functioning
      1 year later. AOP patients fail to show normal age-related increases in
      processing speed, which in turn predicts poorer functional outcomes. This pattern
      is consistent with the view that adolescent brain developmental processes, such
      as myelination, may be disrupted in these patients.

PMID- 22134490
TI  - An expanded model of faculty vitality in academic medicine.
AB  - Many faculty in today's academic medical centers face high levels of stress and
      low career satisfaction. Understanding faculty vitality is critically important
      for the health of our academic medical centers, yet the concept is ill-defined
      and lacking a comprehensive model. Expanding on previous research that examines
      vital faculty in higher education broadly and in academic medical centers
      specifically, this study proposes an expanded model of the unique factors that
      contribute to faculty vitality in academic medicine. We developed an online
      survey on the basis of a conceptual model (N = 564) and used linear regression to
      investigate the fit of the model. We examined the relationships of two predictor
      variables measuring Primary Unit Climate and Leadership and Career and Life
      Management with an overall Faculty Vitality index comprised of three measures:
      Professional Engagement, Career Satisfaction, and Productivity. The findings
      revealed significant predictive relationships between Primary Unit Climate and
      Leadership, Career and Life Management, and Faculty Vitality. The overall model
      accounted for 59% of the variance in the overall Faculty Vitality Index. The
      results provide new insights into the developing model of faculty vitality and
      inform initiatives to support faculty in academic medical centers. Given the
      immense challenges faced by faculty, now more than ever do we need reliable
      evidence regarding what sustains faculty vitality.

PMID- 22134492
TI  - Evaluation of an analytical method for determining phthalate esters in wine
      samples by solid-phase extraction and gas chromatography coupled with ion-trap
      mass spectrometer detector.
AB  - A solid-phase extraction (SPE) method was developed for extraction and analysis
      of six phthalate esters in wine samples using Carbograph 1 sorbent. The SPE
      procedure allowed efficient recovery of the investigated phthalates ranging
      between 78% and 105% with a relative standard deviation (RSD) <=6.5 for an
      ethanolic phthalic acid ester (PAE) standard solution and between 73-71% and 96
      99% with a RSD <=8.4 for red wine samples spiked with 20 and 50 ng mL(-1) of PAE,
      respectively. The adsorption isotherms and breakthrough curves for Carbograph
      1/water solution were reported. Gas chromatography coupled with an ion-trap mass
      spectrometer detector (GC/IT-MS) was used for analysis. The instrumental
      analytical protocol was found to yield a linear calibration in the range 0.01
      10.0 MUg mL(-1) with R(2) values >=0.9992. The limits of detection in GC/IT-MS
      (SIM mode) vary between 0.2 and 14 ng mL(-1) (RSD <=5.6) whereas the limits of
      quantification range between 0.5 and 25 ng mL(-1) (RSD <=5.9); the intra- and
      inter-day repeatabilities calculated as RSD for wine samples, were between 0.9
      7.8 and 1.0-10.5, respectively. The analytical method developed was applied to
      several commercial wine samples. Furthermore, the investigated methods are
      simple, reliable, reproducible, and not expensive.

PMID- 22134493
TI  - Low-temperature direct bonding of glass nanofluidic chips using a two-step plasma
      surface activation process.
AB  - Owing to the well-established nanochannel fabrication technology in 2D nanoscales
      with high resolution, reproducibility, and flexibility, glass is the leading,
      ideal, and unsubstitutable material for the fabrication of nanofluidic chips.
      However, high temperature (~1,000  degrees C) and a vacuum condition are usually
      required in the conventional fusion bonding process, unfortunately impeding the
      nanofluidic applications and even the development of the whole field of
      nanofluidics. We present a direct bonding of fused silica glass nanofluidic chips
      at low temperature, around 200  degrees C in ambient air, through a two-step
      plasma surface activation process which consists of an O(2) reactive ion etching
      plasma treatment followed by a nitrogen microwave radical activation. The low
      temperature bonded glass nanofluidic chips not only had high bonding strength but
      also could work continuously without leakage during liquid introduction driven by
      air pressure even at 450 kPa, a very high pressure which can meet the
      requirements of most nanofluidic operations. Owing to the mild conditions
      required in the bonding process, the method has the potential to allow the
      integration of a range of functional elements into nanofluidic chips during
      manufacture, which is nearly impossible in the conventional high-temperature
      fusion bonding process. Therefore, we believe that the developed low-temperature
      bonding would be very useful and contribute to the field of nanofluidics.

PMID- 22134494
TI  - New Editorial Board members from China.

PMID- 22134495
TI  - Optimization of a dispersive liquid-liquid microextraction method for the
      analysis of benzotriazoles and benzothiazoles in water samples.
AB  - A simple and rapid dispersive liquid-liquid microextraction method has been
      developed for the determination of 11 benzotriazoles and benzothiazoles in water
      samples. Tri-n-butylphosphate (TBP) was used as extractant, thus avoiding the use
      of toxic water-immiscible chlorinated solvents. The influence of several
      variables (e.g., type and volume of dispersant and extraction solvents, sample
      pH, ionic strength, etc.) on the performance of the sample preparation step was
      systematically evaluated. Analytical determinations were carried out by high
      performance liquid chromatography with fluorescence and UV detection and liquid
      chromatography-electrospray ionization-tandem mass spectrometry. The optimized
      method exhibited a good precision level with relative standard deviation values
      between 3.7% and 8.4%. Extraction yields ranging from 67% to 97% were obtained
      for all of these considered compounds. Finally, the proposed method was
      successfully applied to the analysis of benzotriazoles and benzothiazoles in real
      water samples (tap, river, industrial waters, and treated and raw wastewaters).

PMID- 22134496
TI  - Colonic lymphoid nodular hyperplasia in an adolescent.

PMID- 22134497
TI  - Anti-tumor necrosis factor monoclonal antibody therapy for intestinal Behcet
      disease in an adolescent.

PMID- 22134498
TI  - Spectroscopic IR, EPR, and operando DRIFT insights into surface reaction pathways
      of selective reduction of NO by propene over the Co-BEA zeolite.
AB  - Interaction of a Co-BEA catalyst with individual components (NO, C(3)H(6), CO,
      O(2)) and mixtures simulating the real feed of the selective catalytic reduction
      (SCR) of nitric oxide in static and pulse experiments at variable temperatures
      was investigated by means of IR, EPR, and operando DRIFT spectroscopy coupled
      with QMS/GC analysis of the products. Speciation of cobalt active sites into
      Co(II), mono- and polynuclear oxo-cobalt species as well as CoO clusters was
      quantified by IR using CO and NO as probe molecules. The key intermediates, by
      products, and final products of the SCR reaction were identified and their
      spectroscopic signatures ascertained. Based on the spectroscopic operando
      results, a concise mechanistic scheme of the selective catalytic reduction of
      nitric oxide by propene, triggered by a two-electron Co(II)/Co(0) redox couple,
      was developed. It consists of a complex network of the sequential/parallel
      selective reduction steps that are interlocked by the rival nonselective
      oxidation of the intermediates and their thermal decomposition. It has been shown
      that the SCR process is initiated by the chemoselective capture of NO from the
      reaction mixture by the cobalt active sites leading to the cobalt(II)
      dinitrosyls, which in the excess of oxygen are partially oxidized to surface
      nitrates and nitrites. N(2)O is produced by semi-decomposition of the dinitrosyl
      intermediates on the mononuclear centers, whereas NO(2)via NO oxidation on the
      polynuclear oxo-cobalt sites. Cyanide and isocyanate species, formed together
      with propene oxygenates in the course of the C=C bond scission, are the
      mechanistically pivotal reaction intermediates of C(3)H(6) interaction with the
      dinitrosyles and NO(3)(-)/NO(2)(-) surface species. Dinitrogen is produced by
      three main reaction routes involving oxidation of cyanides by NO/NO(2), reduction
      of dinitrosyls, nitrates, and nitrites by propene oxygenates (medium temperature
      range) or their reduction by carbon monoxide (high temperature range).

PMID- 22134500
TI  - Stereoselective synthesis of sugar fused beta-disubstituted gamma-butyro
      lactones: C-spiro-glycosides from 1,2-cyclopropanecarboxylated sugars.
AB  - A stereoselective methodology was developed for the construction of C-spiro
      glycosides in two steps involving bromonium ion activated solvolytic ring opening
      of sugar derived 1,2-cyclopropanecarboxylates followed by a one-pot
      dehydrohalogenation, intramolecular hetero-Michael addition (IHMA) and ester
      hydrolysis. The obtained spirocyclic lactols were further converted to
      enantiomerically pure spirolactones.

PMID- 22134501
TI  - C-reactive protein as predictor for poor outcome after aneurysmal subarachnoid
      haemorrhage.
AB  - BACKGROUND: Aneurysmal subarachnoid haemorrhage (SAH) is a severe disease with
      high case-fatality and morbidity rates. After SAH, the value of C-reactive
      protein (CRP)--an acute phase sensitive inflammatory marker--as a prognostic
      factor has been poorly studied, with conflicting results. In this prospective
      study, we tested whether increased CRP levels increase independently the risk for
      cerebral infarct and poor outcome. METHODS: Previous diseases as well as
      clinical, laboratory and radiological variables were recorded for 178 patients
      with SAH admitted within 48 h and with aneurysms occluded within 60 h after
      bleeding. Plasma CRP was measured, as well as computed tomography (CT) scans
      routinely obtained on admission, in the morning after aneurysm occlusion, and at
      discharge during second week after SAH. Factors predicting occurrence of cerebral
      infarct and poor outcome at 3 months after SAH were tested with multiple logistic
      regression. RESULTS: CRP levels increased significantly (p < 0.001) between
      hospital admission (mean +/- SD, 11.4 +/- 21.3 mg/l) and the postoperative
      morning (27.0 +/- 31.0 mg/l) and then decreased (p < 0.001) during the the second
      week (19.8 +/- 25.0 mg/l). Admission (18.0 +/- 35.7 vs 8.5 +/- 8.4 mg/l) and
      postoperative (41.0 +/- 40.2 vs 21.1 +/- 24.1 mg/l) CRP levels were higher (p <
      0.001) in those with a poor outcome than in those with a favourable outcome, but
      CRP values did not predict delayed cerebral ischaemia or cerebral infarction. CRP
      levels did not independently predict outcome, since these correlated with
      admission clinical grade and occurrence of intraventricular haemorrhage. Higher
      increase in CRP level between admission and postoperative morning, however,
      independently predicted poor outcome (p = 0.004). Part of this increased risk was
      likely due to an appearance of early postoperative cerebral infarction.
      CONCLUSIONS: CRP levels correlate with outcome but do not seem to predict delayed
      cerebral ischaemia or infarction after SAH.

PMID- 22134502
TI  - MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in
      patients with ovarian cancer.
AB  - A single nucleotide polymorphism (SNP309) of MDM2 causes elevated MDM2 levels and
      an attenuation of p53 function. The aim of the present study was to examine the
      clinical relevance of the MDM2 SNP309 in ovarian cancer.MDM2 SNP309 genotype was
      analyzed in 198 patients with primary ovarian cancer. MDM2 expression was
      investigated using immunohistochemistry. A functional yeast-based assay and
      subsequent sequencing were performed to determine p53 mutational status. Of the
      patients, 44.4% (88 of 198) exhibited the common variant (T/T), 40.9% (81 of 198)
      the heterozygous variant (T/G) and 14.7% (29 of 198) the homozygous variant (G/G)
      MDM2 SNP309 genotype. MDM2 SNP309 was not associated with p53 mutational status,
      MDM2 expression, clinicopathological parameters or prognosis. In patients with
      the T allele (T/T and T/G genotype), p53 wild type carcinomas were associated
      with significantly improved recurrence-free (p<0.001) and overall survival
      (p<0.001) as compared to p53 mutant carcinomas. In contrast, p53 mutational
      status did not possess prognostic relevance in G/G carriers. A possible
      functional impairment of the p53 pathway caused by the G/G genotype of the MDM2
      SNP309 may modify the association between p53 mutational status and prognosis in
      ovarian cancer.

PMID- 22134503
TI  - Role of carnitine in the regulation of glucose homeostasis and insulin
      sensitivity: evidence from in vivo and in vitro studies with carnitine
      supplementation and carnitine deficiency.
AB  - BACKGROUND: Although carnitine is best known for its role in the import of long
      chain fatty acids (acyl groups) into the mitochondrial matrix for subsequent beta
      oxidation, carnitine is also necessary for the efflux of acyl groups out of the
      mitochondria. Since intracellular accumulation of acyl-CoA derivatives has been
      implicated in the development of insulin resistance, carnitine supplementation
      has gained attention as a tool for the treatment of insulin resistance. More
      recent studies even point toward a causative role for carnitine insufficiency in
      developing insulin resistance during states of chronic metabolic stress, such as
      obesity, which can be reversed by carnitine supplementation. METHODS: The present
      review provides an overview about data from both animal and human studies
      reporting effects of either carnitine supplementation or carnitine deficiency on
      parameters of glucose homeostasis and insulin sensitivity in order to establish
      the less well-recognized role of carnitine in regulating glucose homeostasis.
      RESULTS: Carnitine supplementation studies in both humans and animals demonstrate
      an improvement of glucose tolerance, in particular during insulin-resistant
      states. In contrast, less consistent results are available from animal studies
      investigating the association between carnitine deficiency and glucose
      intolerance. The majority of studies dealing with this question could either find
      no association or even reported that carnitine deficiency lowers blood glucose
      and improves insulin sensitivity. CONCLUSIONS: In view of the abovementioned
      beneficial effect of carnitine supplementation on glucose tolerance during
      insulin-resistant states, carnitine supplementation might be an effective tool
      for improvement of glucose utilization in obese type 2 diabetic patients.
      However, further studies are necessary to explain the conflicting observations
      from studies dealing with carnitine deficiency.

PMID- 22134504
TI  - Enhancing the immunogenicity of tumour lysate-loaded dendritic cell vaccines by
      conjugation to virus-like particles.
AB  - BACKGROUND: Tumour cell lysates are an excellent source of many defined and
      undefined tumour antigens and have been used clinically in immunotherapeutic
      regimes but with limited success. METHODS: We conjugated Mel888 melanoma lysates
      to rabbit haemorrhagic disease virus virus-like particles (VLP), which can act as
      vehicles to deliver multiple tumour epitopes to dendritic cells (DC) to
      effectively activate antitumour responses. RESULTS: Virus-like particles did not
      stimulate the phenotypic maturation of DC although, the conjugation of lysates to
      VLP (VLP-lysate) did overcome lysate-induced suppression of DC activation. Lysate
      conjugated VLP enhanced delivery of antigenic proteins to DC, while the co
      delivery of VLP-lysates with OK432 resulted in cross-priming of naive T cells,
      with expansion of a MART1(+) population of CD8(+) T cells and generation of a
      specific cytotoxic response against Mel888 tumour cell targets. The responses
      generated with VLP-lysate and OK432 were superior to those stimulated by
      unconjugated lysate with OK432. CONCLUSION: Collectively, these results show that
      the combination of VLP-lysate with OK432 delivered to DC overcomes the
      suppressive effects of lysates, and enables priming of naive T cells with
      superior ability to specifically kill their target tumour cells.

PMID- 22134505
TI  - Risk of prostate cancer in a population-based cohort of men with coeliac disease.
AB  - BACKGROUND: Prostate cancer (PC) is a leading cause of fatal cancer in men in
      developed countries. Coeliac disease (CD) has previously been linked to a raised
      cancer risk, and changes in some exposures following a CD diagnosis might
      hypothetically raise PC risk. METHODS: We identified 10,995 patients with CD who
      had undergone a small intestinal biopsy in 1969-2007. Statistics Sweden then
      identified 54,233 age-matched male reference individuals from the general
      population. PC data were obtained from the Swedish Cancer Register. Hazard ratios
      (HRs) for PC were estimated using Cox regression analysis. RESULTS: During follow
      up, 185 individuals with CD (expected n=200) had an incident diagnosis of PC.
      This corresponds to a HR of 0.92 (0.79-1.08) (with 95% confidence interval) and
      an absolute risk reduction of 15/100,000 person-years among those with CD. An
      increased risk was not observed even when identification of PC began 5 years
      after biopsy. CONCLUSION: Our conclusion is that a CD diagnosis does not
      represent an increased risk for PC.

PMID- 22134506
TI  - Cancer cell proliferation is inhibited by specific modulation frequencies.
AB  - BACKGROUND: There is clinical evidence that very low and safe levels of amplitude
      modulated electromagnetic fields administered via an intrabuccal spoon-shaped
      probe may elicit therapeutic responses in patients with cancer. However, there is
      no known mechanism explaining the anti-proliferative effect of very low intensity
      electromagnetic fields. METHODS: To understand the mechanism of this novel
      approach, hepatocellular carcinoma (HCC) cells were exposed to 27.12 MHz
      radiofrequency electromagnetic fields using in vitro exposure systems designed to
      replicate in vivo conditions. Cancer cells were exposed to tumour-specific
      modulation frequencies, previously identified by biofeedback methods in patients
      with a diagnosis of cancer. Control modulation frequencies consisted of randomly
      chosen modulation frequencies within the same 100 Hz-21 kHz range as cancer
      specific frequencies. RESULTS: The growth of HCC and breast cancer cells was
      significantly decreased by HCC-specific and breast cancer-specific modulation
      frequencies, respectively. However, the same frequencies did not affect
      proliferation of nonmalignant hepatocytes or breast epithelial cells. Inhibition
      of HCC cell proliferation was associated with downregulation of XCL2 and PLP2.
      Furthermore, HCC-specific modulation frequencies disrupted the mitotic spindle.
      CONCLUSION: These findings uncover a novel mechanism controlling the growth of
      cancer cells at specific modulation frequencies without affecting normal tissues,
      which may have broad implications in oncology.

PMID- 22134507
TI  - Arginine deiminase PEG20 inhibits growth of small cell lung cancers lacking
      expression of argininosuccinate synthetase.
AB  - BACKGROUND: Some cancers have been shown to lack expression of argininosuccinate
      synthetase (ASS), an enzyme required for the synthesis of arginine and a possible
      biomarker of sensitivity to arginine deprivation. Arginine deiminase (ADI) is a
      microbial enzyme capable of efficiently depleting peripheral blood arginine.
      METHODS: Argininosuccinate synthetase expression was assessed in human small cell
      lung cancer (SCLC) by immunohistochemistry (IHC), with expression also assessed
      in a panel of 10 human SCLC by qRT-PCR and western blot. Proliferation assays and
      analyses of apoptosis and autophagy assessed the effect of pegylated ADI (ADI
      PEG20) in vitro. The in vivo efficacy of ADI-PEG20 was determined in mice bearing
      SCLC xenografts. RESULTS: Approximately 45% of SCLC tumours and 50% of cell lines
      assessed were negative for ASS. Argininosuccinate synthetase-deficient SCLC cells
      demonstrated sensitivity to ADI-PEG20, which was associated with the induction of
      autophagy and caspase-independent cell death. Arginine deiminase-PEG20 treatment
      of ASS-negative SCLC xenografts caused significant, dose-dependent inhibition of
      tumour growth of both small and established tumours. CONCLUSION: These results
      suggest a role for ADI-PEG20 in the treatment of SCLC, and a clinical trial
      exploring this therapeutic approach in patients with ASS-negative SCLC by IHC has
      now been initiated.

PMID- 22134508
TI  - Phase I study of the histone deacetylase inhibitor entinostat in combination with
      13-cis retinoic acid in patients with solid tumours.
AB  - BACKGROUND: Preclinical studies suggest that histone deacetylase (HDAC)
      inhibitors may restore tumour sensitivity to retinoids. The objective of this
      study was to determine the safety, tolerability, and the pharmacokinetic
      (PK)/pharmacodynamic (PD) profiles of the HDAC inhibitor entinostat in
      combination with 13-cis retinoic acid (CRA) in patients with solid tumours.
      METHODS: Patients with advanced solid tumours were treated with entinostat orally
      once weekly and with CRA orally twice daily * 3 weeks every 4 weeks. The starting
      dose for entinostat was 4 mg m(-2) with a fixed dose of CRA at 1 mg kg(-1) per
      day. Entinostat dose was escalated by 1 mg m(-2) increments. Pharmacokinetic
      concentrations of entinostat and CRA were determined by LC/MS/MS. Western blot
      analysis of peripheral blood mononuclear cells and tumour samples were performed
      to evaluate target inhibition. RESULTS: A total of 19 patients were enroled. The
      maximum tolerated dose (MTD) was exceeded at the entinostat 5 mg m(-2) dose level
      (G3 hyponatremia, neutropenia, and anaemia). Fatigue (G1 or G2) was a common side
      effect. Entinostat exhibited substantial variability in clearance (147%) and
      exposure. CRA trough concentrations were consistent with prior reports. No
      objective responses were observed, however, prolonged stable disease occurred in
      patients with prostate, pancreatic, and kidney cancer. Data further showed
      increased tumour histone acetylation and decreased phosphorylated ERK protein
      expression. CONCLUSION: The combination of entinostat with CRA was reasonably
      well tolerated. The recommended phase II doses are entinostat 4 mg m(-2) once
      weekly and CRA 1 mg kg(-1) per day. Although no tumour responses were seen,
      further evaluation of this combination is warranted.

PMID- 22134509
TI  - Cytology of the vulva: feasibility and preliminary results of a new brush.
AB  - OBJECTIVE: Taking a biopsy is a standard procedure to make the correct diagnosis
      in patients with suspicious premalignant vulvar lesions. The use of a less
      invasive diagnostic tool as triage instrument to determine whether biopsy is
      necessary may improve patient comfort especially in patients with chronic vulvar
      disorders that may warrant consecutive biopsies. This study was conducted to
      investigate whether vulvar brush cytology is feasible and may be used to detect
      (pre)malignant vulvar lesions. METHODS: A pilot study was performed with patients
      having clinically normal vulvar skin, lichen sclerosus (LS), usual or
      differentiated vulvar intraepithelial neoplasia or squamous cell carcinoma. A
      total of 65 smears were taken with the use of a vulvar brush and biopsies were
      performed for histopathological analysis. RESULTS: Out of 65 smears, 17 (26%)
      were discarded because of poor cellularity. A total of 28 of 29 (97%) smears with
      a histological proven (pre)malignancy had a smear classified as 'suspicious' or
      'uncertain'. Cytology classified 11 smears as 'non-suspicious', of which 10 (91%)
      were indeed normal skin or LS. The accuracy, based on the presence of a lesion,
      for (pre)malignant lesions with the use of the brush showed a sensitivity of 97%
      and a negative predictive value of 88%. CONCLUSION: Vulvar brush cytology is
      feasible and may be a first step in the development of a triage instrument to
      determine whether subsequent biopsy of a clinically (pre)malignant lesion is
      necessary.

PMID- 22134510
TI  - Investigating prostate cancer tumour-stroma interactions: clinical and biological
      insights from an evolutionary game.
AB  - BACKGROUND: Tumours are made up of a mixed population of different types of cells
      that include normal structures as well as ones associated with the malignancy,
      and there are multiple interactions between the malignant cells and the local
      microenvironment. These intercellular interactions, modulated by the
      microenvironment, effect tumour progression and represent a largely under
      appreciated therapeutic target. We use observations of primary tumour biology
      from prostate cancer to extrapolate a mathematical model. Specifically, it has
      been observed that in prostate cancer three disparate cellular outcomes
      predominate: (i) the tumour remains well differentiated and clinically indolent-
      in this case the local stromal cells may act to restrain the growth of the
      cancer; (ii) early in its genesis the tumour acquires a highly malignant
      phenotype, growing rapidly and displacing the original stromal population (often
      referred to as small cell prostate cancer)--these less common aggressive tumours
      are relatively independent of the local microenvironment and (iii) the tumour co
      opts the local stroma--taking on a classic stromagenic phenotype where
      interactions with the local microenvironment are critical to the cancer growth.
      METHODS: We present an evolutionary game theoretical construct that models the
      influence of tumour-stroma interactions in driving these outcomes. We consider
      three characteristic and distinct cellular populations: stromal cells, tumour
      cells that are self-reliant in terms of microenvironmental factors and tumour
      cells that depend on the environment for resources, but can also co-opt stroma.
      RESULTS: Using evolutionary game theory we explore a number of different
      scenarios that elucidate the impact of tumour-stromal interactions on the
      dynamics of prostate cancer growth and progression, and how different treatments
      in the metastatic setting can affect different types of tumours. CONCLUSION: The
      tumour microenvironment has a crucial role in selecting the traits of the tumour
      cells that will determine prostate cancer progression. Equally important
      treatments like hormone therapy affect the selection of these cancer phenotypes
      making it very important to understand how they impact prostate cancer's somatic
      evolution.

PMID- 22134512
TI  - A phase III study of late course accelerated hyperfractionated radiotherapy
      versus conventionally fractionated radiotherapy in patients with nasopharyngeal
      carcinoma.
AB  - OBJECTIVE: To compare the efficacy and toxicity of late course accelerated
      hyperfractionated radiotherapy (LCAF) with conventionally fractionated (CF)
      radiotherapy in the treatment of nasopharyngeal carcinoma (NPC). METHODS: Between
      March 1998 and November 2002, 200 eligible patients with NPC were randomized to
      receive either LCAF (48 Gy in 40 fractions, 2 fractions per day, 1.2 Gy/fraction,
      with an interval of >=6 h, 5 d/wk, followed by 30 Gy in 20 fractions using 2
      fractions per day, 1.5 Gy/fraction, 5 d/wk) or CF (35 fractions, 2.0
      Gy/fraction/d, 5 d/wk, to a total dose of 70 Gy). RESULTS: All patients completed
      the treatment. Overall baseline characteristics of the study population of the 2
      arms were well balanced. With a median follow-up of 6.9 years, the 5-year local
      control rate was higher in the LCAF arm (87.6% vs. 75.9%, P=0.044). The 5-year
      overall survival rates were 74.1% vs. 58.0% (P=0.024) for the LCAF arm and the CF
      arm, respectively. LCAF patients had a higher occurrence of acute mucositis and a
      more evident weight loss than CF patients, whereas incidence rates of radiation
      induced damage to the central nervous system were similar in the 2 arms.
      CONCLUSIONS: LCAF achieved higher local control and overall survival rates than
      CF radiotherapy, without increasing radiation-related late complications such as
      cranial nerve palsy.

PMID- 22134511
TI  - The GOFURTGO Study: AGITG phase II study of fixed dose rate gemcitabine
      oxaliplatin integrated with concomitant 5FU and 3-D conformal radiotherapy for
      the treatment of localised pancreatic cancer.
AB  - BACKGROUND: Locally advanced inoperable pancreatic cancer (LAPC) has a poor
      prognosis. By increasing intensity of systemic therapy combined with an
      established safe chemoradiation technique, our intention was to enhance the
      outcomes of LAPC. In preparation for phase III evaluation, the feasibility and
      efficacy of our candidate regimen gemcitabine-oxaliplatin chemotherapy with
      sandwich 5-fluorouracil (5FU) and three-dimensional conformal radiotherapy
      (3DCRT) needs to be established. METHODS: A total of 48 patients with inoperable
      LAPC without metastases were given gemcitabine (1000 mg m(-2) d1 + d15 q28) and
      oxaliplatin (100 mg m(-2) d2 + d16 q28) in induction (one cycle) and
      consolidation (three cycles), and 5FU 200 mg m(-2) per day over 6 weeks during
      3DCRT 54 Gy. RESULTS: Median duration of sustained local control (LC) was 15.8
      months, progression-free survival (PFS) was 11.0 months, and overall survival was
      15.7 months. Survival rates for 1, 2, and 3 years were 70.2%, 21.3%, and 12.8%,
      respectively. Global quality of life did not significantly decline from baseline
      during treatment, which was associated with modest treatment-related toxicity.
      CONCLUSION: Fixed-dose gemcitabine and oxaliplatin, combined with an effective
      and safe regimen of 5FU and 3DCRT radiotherapy, was feasible and reasonably
      tolerated. The observed improved duration of LC and PFS with more intensive
      therapy over previous trials may be due to patient selection, but suggest that
      further evaluation in phase III trials is warranted.

PMID- 22134513
TI  - Stereotactic body radiation for the spine: a review.
AB  - Stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) for
      spinal metastases are emerging treatment paradigms in the multidisciplinary
      management of metastases located within or adjacent (paraspinal) to the vertebral
      bodies/spinal cord. In this review, we provide a brief overview of spine SBRT/SRS
      indications, technology, planning, and treatment delivery; review the current
      state of the literature; and discuss the radiobiology, toxicity, and limitations
      of SBRT/SRS for metastatic disease of the spine. 

PMID- 22134514
TI  - The impact of diabetes mellitus on survival in men with clinically localized
      prostate cancer treated with permanent interstitial brachytherapy.
AB  - PURPOSE: Patients with cancer of any origin with preexisting diabetes mellitus
      (DM) are at increased risk for all-cause mortality compared with those without
      DM. However, the influence of DM on biochemical progression-free survival (bPFS),
      cause-specific survival (CSS), and overall survival (OS) has not been clearly
      defined for men with clinically localized prostate cancer treated with
      brachytherapy. MATERIALS AND METHODS: From April 1995 to May 2006, 1624
      consecutive patients underwent brachytherapy with or without supplemental
      therapies. A prebrachytherapy diagnosis of diabetes was present in 199 patients
      (12.3%). Median follow-up was 7.8 years. Cause of death was determined for each
      deceased patient. Patients with metastatic prostate cancer or castrate-resistant
      disease without obvious metastases who died of any cause were classified as dead
      of prostate cancer. All other deaths were attributed to the immediate cause of
      death. RESULTS: In patients without (n=1425) and with (n=199) DM, CSS was 97.2%
      versus 100% (P=0.168), bPFS was 95.6% versus 95.7% (P=0.960), and OS was 77.3%
      versus 56.0% at 12 years (P=0.003). In Cox regression analysis, OS in nondiabetic
      patients was most closely related to patient age, coronary artery disease,
      tobacco consumption, and androgen deprivation. In patients with diabetes, OS was
      related to patient age and coronary artery disease. In patients without diabetes,
      CSS was associated with Gleason score and clinical stage. No patient with
      diabetes died of prostate cancer. Patients with DM were more likely to die of
      cardiovascular disease (17.8% vs. 12.4%, P=0.007). CONCLUSIONS: DM does not
      impact CSS or bPFS after brachytherapy. OS is significantly lower in patients
      with diabetes due to more deaths from cardiovascular disease.

PMID- 22134515
TI  - Transtympanic injections of N-acetylcysteine for the prevention of cisplatin
      induced ototoxicity: a feasible method with promising efficacy.
AB  - OBJECTIVES: Ototoxicity is a common and irreversible adverse effect of cisplatin
      treatment with great impact on the patients' quality of life. N-acetylcysteine is
      a low-molecular-weight agent which has shown substantial otoprotective activity.
      The role of transtympanic infusions of N-acetylcysteine was examined in a cohort
      of patients treated with cisplatin-based regimens. PATIENTS AND METHODS: Twenty
      cisplatin-treated patients were subjected, under local anesthesia, to
      transtympanic N-acetylcysteine (10%) infusions in 1 ear, during the hydration
      procedure preceding intravenous effusion of cisplatin. The contralateral ear was
      used as control. The number of transtympanic infusions was respective to the
      number of administered cycles. Hearing acuity was evaluated before each cycle
      with pure tone audiometry by an audiologist blinded to the treated ear. RESULTS:
      A total of 84 transtympanic infusions were performed. In treated ears, no
      significant changes in auditory thresholds were recorded. In the control ears
      cisplatin induced a significant decrease of auditory thresholds at the 8000 Hz
      frequency band (P=0.008). At the same frequency (8000 Hz), the changes in
      auditory thresholds were significantly larger for the control ears than the
      treated ones (P=0.005). An acute pain starting shortly after the injection and
      lasting for a few minutes seemed to be the only significant adverse effect.
      CONCLUSIONS: Transtympanic injections of N-acetylcysteine seem to be a feasible
      and effective otoprotective strategy for the prevention of cisplatin-induced
      ototoxicity. Additional studies are required to further clarify the efficiency of
      this treatment and determine the optimal dosage and protocol.

PMID- 22134516
TI  - Rationale of excisional biopsy after the diagnosis of benign radial scar on core
      biopsy: a single institutional outcome analysis.
AB  - BACKGROUND: Radial scar (RS) is characterized by a fibroelastic core with
      entrapped ducts and lobules. Association with carcinoma is not uncommon. There is
      some dilemma as to the need for excisional biopsy or follow-up after RS diagnosis
      on core biopsy. AIM: To determine the necessity of excisional biopsy after the
      diagnosis of benign RS by core biopsy. STUDY DESIGN: A total of 67 RS specimens
      associated with benign findings on core biopsy obtained between 2003 and 2008
      were reviewed. They were grouped by their accompanying histopathologic features
      found upon subsequent surgical excision: benign, high-risk lesion (HRL), or
      carcinoma. Demographic features, radiologic findings, and needle gauge were
      compared within subgroups. RESULTS: After surgical excision, 15 (22.4%) patients
      in the benign group were upgraded to a HRL, 4 (5.9%) patients were upgraded to
      carcinoma, and 48 (71.6%) remained benign. We found that malignancy is associated
      with RS more frequently if the patient is older and postmenopausal. Other
      variables such as symptoms at presentation, presence and type of abnormality on
      mammography (Breast Imaging Reporting and Data System score), breast density,
      size of biopsy needle used, and number of core samples retrieved did not help to
      predict the presence of carcinoma. CONCLUSIONS: The HRL and cancer upgrade rate
      of RS, requiring further intervention such as surgery or chemoprevention, is 28%
      in this study. However, we found that age and menopausal status may be taken into
      consideration when making the decision to follow up or excise the RS diagnosed on
      core biopsy. There is insufficient data to support the predictive value of any
      variables. Therefore, RS associated with benign findings on core biopsy should be
      excised.

PMID- 22134517
TI  - Improving the therapeutic ratio by using proton therapy in patients with stage I
      or II seminoma.
AB  - OBJECTIVES: The goal of the present study was to evaluate possible dosimetric
      advantages of proton therapy (PT) compared with 3-dimensional conformal
      radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in the treatment
      of patients with stage I and II seminoma. METHODS: Two representative patients (1
      with left-sided and 1 with right-sided seminoma) underwent treatment planning for
      stage I seminoma (paraaortic lymph nodes alone) with 3DCRT (PA3d), IMRT (PAimrt)
      double-scatter protons (PAPds), and uniform-scanning protons (PAPus) and for
      stage II seminoma (paraaortics lymph nodes and iliac nodes) with 3DCRT (PI3d) ,
      IMRT (PIimrt) double-scatter protons (PIPds), and uniform-scanning protons
      (PIPus). The doses to the organs at risk were compared for photons and protons.
      RESULTS: For stage I seminoma, PT reduced the mean dose to the stomach,
      ipsilateral kidney, pancreas, bowel space, small bowel, and colon compared with
      3DCRT and IMRT. For stage II seminoma, PT reduced the mean dose to the same
      organs as in stage I seminoma with additional reductions in mean dose to the
      bladder and rectum compared with 3DCRT and IMRT. Uniform-scanning protons further
      reduced the dose to the organs at risk compared with double-scatter protons.
      CONCLUSIONS: PT may offer an improvement in the therapeutic ratio in patients
      with seminoma by reducing the dose to normal tissue. This improvement may
      translate into lower risks of acute gastrointestinal side effects, infertility,
      and secondary malignancies, which should be explored in a prospective study.

PMID- 22134518
TI  - Primary pancreatic lymphoma: a population-based analysis using the SEER program.
AB  - BACKGROUND: Primary pancreatic lymphoma (PPL) is a rare disease, accounting for
      only 0.5% of all pancreatic masses. A paucity of literature exists on the
      epidemiology and outcomes of PPL. Here, we present a series of 523 cases of PPL
      obtained from the Surveillance, Epidemiology, and End Results database. METHODS:
      Patients diagnosed with a PPL from 1973 to 2007 were identified. Data on patient
      and tumor characteristics as well as initial treatment with surgery or radiation
      were extracted. Survival rates were calculated using the Kaplan-Meier method. A
      multivariate analysis was performed to determine independent prognostic factors
      predicting mortality hazard ratios using Cox proportional hazards modeling.
      RESULTS: Fifty-eight percent of patients identified were male. The median age
      range at diagnosis was 65 to 69 years. The most common histologic subtype in the
      present series was diffuse large B-cell lymphoma, which accounted for 56% of all
      patients. The 5-year overall survival for the group was 45%. Multivariate
      analysis suggests that age more than 60 years at diagnosis, race of "other"
      (compared with "white"), and marital status of single or widowed were predictive
      of increased all-cause mortality (P<0.05). CONCLUSIONS: This represents the
      largest published series of patients with PPL. Age more than 60 years, female
      sex, and marital status of married were identified as independent prognostic
      factors predicting for decreased all-cause mortality.

PMID- 22134519
TI  - Complication rates in patients with negative axillary nodes 10 years after local
      breast radiotherapy after either sentinel lymph node dissection or axillary
      clearance.
AB  - BACKGROUND: We assess complication rates in node negative breast cancer patients
      treated with breast radiotherapy (RT) only after sentinel lymph node dissection
      (SLND) or axillary lymph node dissection (ALND). MATERIALS AND METHODS: Between
      1995 and 2001, 226 women with AJCC stage I-II breast cancer were treated with
      lumpectomy, either SLND or SLND+ALND, and had available toxicities in follow-up:
      111/136 (82%) and 115/129 (89%) in SLND and ALND groups, respectively. RT
      targeted the breast to median dose of 48.2 Gy (range, 46.0 to 50.4 Gy) without
      axillary RT. Chi-square tests compared complication rates of 2 groups for
      axillary web syndrome (AWS), seroma, wound infection, decreased range of motion
      of the ipsilateral shoulder, paresthesia, and lymphedema. RESULTS: Median follow
      up was 9.9 years (range, 8.3-15.3 y). Median number of nodes assessed was 2
      (range, 1-5) in SLND and 18 (range, 7-36) in ALND (P < 0.0001). Acute
      complications occurred during the first 2 years and were AWS, seroma, and wound
      infection. Incidences of seroma 5/111 (4.5%) in SLND and 16/115 (13.9%) in ALND
      (P < 0.02, respectively) and wound infection 3/111 (2.7%) in SLND and 10/115
      (8.7%) in ALND (P < 0.05, respectively) differed significantly. AWS was not
      statistically different between the groups. At 10 years, the only chronic
      complications decreased were range of motion of the shoulder 46/111 (41.4%) in
      SLND and 92/115 (80.0%) in ALND (P < 0.0001), paresthesia 12/111 (10.8%) in SLND
      and 39/115 (33.9%) in ALND (P < 0.0001), and lymphedema assessed by patients
      10/111 (10.0%) in SLND and 39/115 (33.9%) in ALND (P < 0.0001). Chronic
      lymphedema, assessed by clinicians, occurred in 6/111 (5.4%) in SLND and 21/115
      (18.3%) in ALND cohorts, respectively (P < 0.0001). CONCLUSIONS: Our mature
      findings support that in patients with negative axillary nodal status SLND and
      breast RT provide excellent long-term cure rates while avoiding morbidities
      associated with ALND or addition of axillary RT field.

PMID- 22134520
TI  - Absolute and relative kinetic changes of high-sensitivity cardiac troponin T in
      acute coronary syndrome and in patients with increased troponin in the absence of
      acute coronary syndrome.
AB  - BACKGROUND: We evaluated kinetic changes of high-sensitivity cardiac troponin T
      (hs-cTnT) in patients with acute coronary syndrome (ACS) and patients with hs
      cTnT increases not due to ACS to rule in or rule out non-ST-segment elevation
      myocardial infarction (STEMI). METHODS: hs-cTnT was measured serially in
      consecutive patients presenting to the emergency department. Patients with ACS
      who had at least 2 hs-cTnT measurements within 6 h and non-ACS patients with hs
      cTnT concentrations above the 99th percentile value (14 ng/L) were enrolled to
      compare absolute and relative kinetic changes of hs-cTnT. RESULTS: For
      discrimination of non-STEMI (n=165) in the entire study population (n=784), the
      absolute delta change with the ROC-optimized value of 9.2 ng/L yielded an area
      under the curve of 0.898 and was superior to all relative delta changes
      (P<0.0001). The positive predictive value for the absolute delta change was
      48.7%, whereas the negative predictive value was 96.5%. In a specific ACS
      population with exclusion of STEMI (n=342), the absolute delta change with the
      ROC-optimized value of 6.9 ng/L yielded a positive predictive value of 82.8% and
      a negative predictive value of 93.0%. In comparison to the >=20% relative delta
      change, the ROC-optimized absolute delta change demonstrated a significantly
      added value for the entire study population and for the ACS cohort (net
      reclassification index 0.331 and 0.499, P<0.0001). CONCLUSIONS: Absolute delta
      changes appear superior to relative delta changes in discriminating non-STEMI. A
      rise or fall of at least 9.2 ng/L in the entire study population and 6.9 ng/L in
      selected ACS patients seems adequate to rule-out non-STEMI. However, delta-values
      are useful to rule-in non-STEMI only in a specific ACS population.

PMID- 22134521
TI  - Using systems of care to reduce incarceration of youth with serious mental
      illness.
AB  - Youth with serious mental illness come into contact with juvenile justice more
      than 3 times as often as other youth, obliging communities to expend substantial
      resources on adjudicating and incarcerating many who, with proper treatment,
      could remain in the community for a fraction of the cost. Incarceration is
      relatively ineffective at remediating behaviors associated with untreated serious
      mental illness and may worsen some youths' symptoms and long-term prognoses.
      Systems of care represent a useful model for creating systems change to reduce
      incarceration of these youth. This paper identifies the systemic factors that
      contribute to the inappropriate incarceration of youth with serious mental
      illness, including those who have committed non-violent offenses or were detained
      due to lack of available treatment. It describes the progress of on-going efforts
      to address this problem including wraparound and diversion programs and others
      utilizing elements of systems of care. The utility of systems of care principles
      for increasing access to community-based mental health care for youth with
      serious mental illness is illustrated and a number of recommendations for
      developing collaborations with juvenile justice to further reduce the
      inappropriate incarceration of these youth are offered.

PMID- 22134522
TI  - Co-variation of ionic conductances supports phase maintenance in stomatogastric
      neurons.
AB  - Neuronal networks produce reliable functional output throughout the lifespan of
      an animal despite ceaseless molecular turnover and a constantly changing
      environment. Central pattern generators, such as those of the crustacean
      stomatogastric ganglion (STG), are able to robustly maintain their functionality
      over a wide range of burst periods. Previous experimental work involving
      extracellular recordings of the pyloric pattern of the STG has demonstrated that
      as the burst period varies, the inter-neuronal delays are altered proportionally,
      resulting in burst phases that are roughly invariant. The question whether spike
      delays within bursts are also proportional to pyloric period has not been
      explored in detail. The mechanism by which the pyloric neurons accomplish phase
      maintenance is currently not obvious. Previous studies suggest that the co
      regulation of certain ion channel properties may play a role in governing
      neuronal activity. Here, we observed in long-term recordings of the pyloric
      rhythm that spike delays can vary proportionally with burst period, so that spike
      phase is maintained. We then used a conductance-based model neuron to determine
      whether co-varying ionic membrane conductances results in neural output that
      emulates the experimentally observed phenomenon of spike phase maintenance. Next,
      we utilized a model neuron database to determine whether conductance correlations
      exist in model neuron populations with highly maintained spike phases. We found
      that co-varying certain conductances, including the sodium and transient calcium
      conductance pair, causes the model neuron to maintain a specific spike phase
      pattern. Results indicate a possible relationship between conductance co
      regulation and phase maintenance in STG neurons.

PMID- 22134524
TI  - Color modeling of protein optical probes.
AB  - We present a strategy for modeling optical probes within heterogeneous
      environments of restricted dimension. The method is based on a multiphysics
      approach comprising sequential structure modeling by means of hybrid Car
      Parrinello molecular dynamics and property modeling by means of quantum
      mechanics/molecular mechanics response theory. For demonstration we address the
      structural and optical properties of nile red within the beta-lacto globulin
      protein. We consider the cases with the probe situated on the surface or within
      the cavity of the protein, or embedded in a water solvent. We find the absorption
      properties of the probe to be highly dependent on its position relative to the
      protein. Structural rearrangements of the optical probe are found to contribute
      significantly to these environmental effects.

PMID- 22134525
TI  - EMA's reflection on placebo does not reflect patients' interests.

PMID- 22134526
TI  - Assessment of infection with polyomaviruses BKV, JCV and SV40 in different groups
      of Cuban individuals.
AB  - We investigated the frequency of BKV, JCV and SV40 reactivation in three groups
      of Cuban patients by multiplex nested PCR assay of 40 paraffin-embedded
      colorectal neoplasm tissues, 113 urine samples, and 125 plasma samples from 27
      transplant recipients, and cerebrospinal fluid (CSF) from 67 HIV-1-infected
      individuals with central nervous system (CNS) disorders. None of these
      polyomaviruses were detected in colorectal neoplasms. JCV DNA was detected in 2
      of 67 patients (2.9%) with CNS disorders, but neither BKV nor SV40 was
      identified. BKV was found in urine from 38.5% and 28.6% of adult and pediatric
      transplant recipients, respectively. In adult renal transplant recipients,
      excretion of BKV in urine was significantly associated with episodes of acute
      rejection (p=0.012) and with excretion of HCMV in urine (p= 0.008). In Cuba, the
      polyomaviruses studied here could not be related to colorectal neoplasms, and JCV
      was rarely detected in CSFs of HIV-1-infected individuals, whilst BKV
      reactivation was found to occur frequently in organ transplant recipients.

PMID- 22134527
TI  - Complete genome sequence of a banana bract mosaic virus isolate infecting the
      French plantain cv. Nendran in India.
AB  - The first complete genome sequence of an Indian isolate (TRY) of Banana bract
      mosaic virus (BBrMV) was determined following virus RNA extraction from the
      French plantain cv. Nendran (AAB). The complete genome was 9711 nucleotides
      excluding the poly(A) tail and had a genome organization similar to that of a
      Philippine (PHI) isolate characterized earlier. When compared to BBrMV-PHI, the
      complete genome sequence of BBrMV-TRY was 94% identical at the nucleotide level
      and its ten mature proteins had amino acid sequence identities ranging from 88 to
      98%. Phylogenetic analysis suggests that the BBrMV-TRY isolate is closely related
      to the BBrMV-PHI isolate.

PMID- 22134528
TI  - DNA binding and nucleolytic properties of Cu(ii) complexes of salicylaldehyde
      semicarbazones.
AB  - The copper(ii) complexes of two salicylaldehyde semicarbazones,
      HOC(6)H(4)CH[double bond, length as m-dash]N-NHCONR(2) [H(2)Bnz(2) (R = CH(2)Ph)
      and H(2)Bu(2) (R = Bu)], were evaluated for their DNA binding and cleavage
      properties by spectrophotometric DNA titration, ethidium bromide displacement
      assay and electrophoretic mobility shift assay. Results showed that the Cu(ii)
      complexes can bind to DNA via a partial intercalation mode with binding constants
      of 1.1 * 10(4) and 9.5 * 10(3) M(-1) for [Cu(HBnz(2))Cl] and [Cu(HBu(2))Cl],
      respectively. These complexes also cleave DNA in the presence of ascorbic acid,
      most likely through hydroxyl radicals that are generated via the reduction of a
      Cu(ii) to a Cu(i) species. The complexes show similar DNA cleavage activity,
      which is reflected in the similarity of their frontier molecular orbital energies
      calculated by density functional theory. These results are discussed in relation
      to the anticancer properties of the complexes.

PMID- 22134529
TI  - microRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated
      with liver metastasis in colorectal cancer.
AB  - MicroRNAs (miRNAs) have been implicated in regulating diverse cellular pathways.
      Although there is emerging evidence that various miRNAs function as oncogenes or
      tumor suppressors in colorectal cancer (CRC), the role of miRNAs in mediating
      liver metastasis remains unexplored. The expression profile of miRNAs in liver
      metastasis and primary CRC tissues was analyzed by miRNA microarrays and verified
      by real-time polymerase chain reaction (PCR). In 62 CRC patients, the expression
      levels of miR-320a were determined by real-time PCR, and the effects on migration
      and invasion of miR-320a were determined using a transwell assay. miR-320a target
      genes were confirmed by luciferase assay, real-time PCR and western blot
      analysis. A set of miRNAs was found to be dysregulated in the liver metastasis
      tissues compared to matched primary CRC tissues, and the expression levels of miR
      320a were significantly decreased in the liver metastasis tissues examined. miR
      320a was correlated with tumor progression in CRC. miR-320a was downregulated in
      liver metastatic colon cancer cells and inhibited liver metastatic colon cancer
      cell migration and invasion. miR-320a directly binds to the 3'UTR of neuropilin 1
      (NRP-1), a protein that functions as a co-receptor of vascular epithelial growth
      factor. miR-320a downregulated the expression of NRP-1 at both the mRNA and
      protein levels. These data demonstrated that miR-320a may be useful for
      identifying CRC patients that are at an elevated risk for developing liver
      metastasis. Our findings suggest that miR-320a may be a novel therapeutic
      candidate for the treatment of colorectal cancer.

PMID- 22134530
TI  - RNase MC2: a new Momordica charantia ribonuclease that induces apoptosis in
      breast cancer cells associated with activation of MAPKs and induction of caspase
      pathways.
AB  - Ribonucleases (RNases) are ubiquitously distributed nucleases that cleave RNA
      into smaller pieces. They are promising drugs for different cancers based on
      their concrete antitumor activities in vitro and in vivo. Here we report for the
      first time purification and characterization of a 14-kDa RNase, designated as
      RNase MC2, in the seeds of bitter gourd (Momordica charantia). RNase MC2
      manifested potent RNA-cleavage activity toward baker's yeast tRNA, tumor cell
      rRNA, and an absolute specificity for uridine. RNase MC2 demonstrated both
      cytostatic and cytotoxic activities against MCF-7 breast cancer cells. Treatment
      of MCF-7 cells with RNase MC2 caused nuclear damage (karyorrhexis, chromatin
      condensation, and DNA fragmentation), ultimately resulting in early/late
      apoptosis. Further molecular studies unveiled that RNase MC2 induced differential
      activation of MAPKs (p38, JNK and ERK) and Akt. On the other hand, RNase MC2
      exposure activated caspase-8, caspase-9, caspase-7, increased the production of
      Bak and cleaved PARP, which in turn contributed to the apoptotic response. In
      conclusion, RNase MC2 is a potential agent which can be exploited in the
      worldwide fight against breast cancer.

PMID- 22134533
TI  - Introducing chemiluminescence resonance energy transfer into immunoassay in a
      microfluidic format for an improved assay sensitivity.
AB  - We report on a novel strategy to improve microfluidic immunoassay sensitivity by
      introducing chemiluminescence resonance energy transfer (CRET) into the
      immunoreactions. The proposed CRET-based immunoassay for estradiol (E2, as a
      model analyte) is one of the most sensitive immunoassay with a limit of detection
      at 3.6 * 10(-11) M E2 in a microfluidic format.

PMID- 22134534
TI  - Exceptionally strong Bragg diffraction from a mesoporous silica film pretreated
      with chlorotrimethylsilane toward application in X-ray optics.
AB  - Exceptionally strong Bragg diffraction from a mesoporous silica film is achieved
      by exposing the as-deposited film to vapor of chlorotrimethylsilane (Me(3)SiCl)
      before extracting the surfactant. The intensity of the X-ray diffraction peak
      increased 7 times after the surfactant removal and it approached 30%
      reflectivity. This large increase of diffraction intensity cannot be explained
      simply by the improved contrast of the electron density, and rearrangement of the
      pore wall during the Me(3)SiCl vapor treatment is suggested. It is shown by
      infrared spectroscopy that Me(3)SiCl with a high grafting reactivity effectively
      caps the silanol groups and prevents the following condensation, which causes the
      structural degradation. The substitution of the hydrogen atom of hydroxyl groups
      with trimethylsilyl groups should help the improvement of the structural
      regularity by reducing the hydrogen bonds in the pore wall. The achieved strong
      diffraction opens the gate for the application of these regular mesoporous films
      prepared by a self-assembly process to optical elements in the X-ray region.

PMID- 22134535
TI  - 18F-FDG PET/CT compared to conventional imaging modalities in pediatric primary
      bone tumors.
AB  - BACKGROUND: F-Fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography (PET)
      is useful in adults with primary bone tumors. Limited published data exist in
      children. OBJECTIVE: To compare hybrid FDG positron emission tomography/computed
      tomography (PET/CT) with conventional imaging (CI) modalities in detecting
      malignant lesions, predicting response to chemotherapy and diagnosing physeal
      involvement in pediatric primary bone tumors. MATERIALS AND METHODS:
      Retrospective analysis of PET/CT and CI reports with histopathology or follow-up
      > 6 months as reference standard. Response parameters and physeal involvement at
      diagnosis were compared to histopathology. RESULTS: A total of 314 lesions were
      detected in 86 scans. Excluding lung lesions, PET/CT had higher sensitivity and
      specificity than CI (83%, 98% and 78%, 97%, respectively). In lung lesions,
      PET/CT had higher specificity than CI (96% compared to 87%) but lower sensitivity
      (80% compared to 93%). Higher initial SUV(max) and greater SUV(max) reduction on
      PET/CT after chemotherapy predicted a good response. Change in tumor size on MRI
      did not predict response. Both PET/CT and MRI were very sensitive but of low
      specificity in predicting physeal tumor involvement. CONCLUSION: PET/CT appears
      more accurate than CI in detecting malignant lesions in childhood primary bone
      tumors, excluding lung lesions. It seems better than MRI at predicting tumor
      response to chemotherapy.

PMID- 22134536
TI  - Prenatal imaging of amniotic band sequence: utility and role of fetal MRI as an
      adjunct to prenatal US.
AB  - BACKGROUND: Amniotic band sequence and its US manifestations have been well
      described. There is little information, however, regarding the accuracy and
      utility of fetal MRI. OBJECTIVE: To describe the MRI findings in amniotic band
      sequence and to compare the diagnostic accuracy of MRI and US. MATERIALS AND
      METHODS: Prenatal MRI and US studies were retrospectively reviewed in 14
      consecutive pregnancies with confirmed amniotic band sequence. Both studies were
      evaluated for amniotic band visualization, body part affected, type of deformity,
      umbilical cord involvement and vascular abnormality. RESULTS: Amniotic bands were
      confidently identified with MRI in 8 fetuses (57%), suggested with MRI in 3
      fetuses (21%) and confidently seen by US in 13 fetuses (93%). Neither modality
      detected surgically proven bands on one fetus. Both techniques were equally able
      to define the body part affected and the type of deformity. At least one limb
      abnormality was visualized in all cases and truncal involvement was present in
      two cases. Cord involvement was identified in seven cases, with one case detected
      only by MRI. CONCLUSION: Fetal MRI is able to visualize amniotic bands and their
      secondary manifestations and could be complementary to prenatal US when fetal
      surgery is contemplated.

PMID- 22134537
TI  - Molecular subgroups of medulloblastoma: the current consensus.
AB  - Medulloblastoma, a small blue cell malignancy of the cerebellum, is a major cause
      of morbidity and mortality in pediatric oncology. Current mechanisms for clinical
      prognostication and stratification include clinical factors (age, presence of
      metastases, and extent of resection) as well as histological subgrouping
      (classic, desmoplastic, and large cell/anaplastic histology). Transcriptional
      profiling studies of medulloblastoma cohorts from several research groups around
      the globe have suggested the existence of multiple distinct molecular subgroups
      that differ in their demographics, transcriptomes, somatic genetic events, and
      clinical outcomes. Variations in the number, composition, and nature of the
      subgroups between studies brought about a consensus conference in Boston in the
      fall of 2010. Discussants at the conference came to a consensus that the evidence
      supported the existence of four main subgroups of medulloblastoma (Wnt, Shh,
      Group 3, and Group 4). Participants outlined the demographic, transcriptional,
      genetic, and clinical differences between the four subgroups. While it is
      anticipated that the molecular classification of medulloblastoma will continue to
      evolve and diversify in the future as larger cohorts are studied at greater
      depth, herein we outline the current consensus nomenclature, and the differences
      between the medulloblastoma subgroups.

PMID- 22134538
TI  - MicroRNA-182 promotes leptomeningeal spread of non-sonic hedgehog
      medulloblastoma.
AB  - The contribution of microRNAs to the initiation, progression, and metastasis of
      medulloblastoma (MB) remains poorly understood. Metastatic dissemination at
      diagnosis is present in about 30% of MB patients, and is associated with a dismal
      prognosis. Using microRNA expression profiling, we demonstrate that the retinal
      miR-183-96-182 cluster on chromosome 7q32 is highly overexpressed in non-sonic
      hedgehog MBs (non-SHH-MBs). Expression of miR-182 and miR-183 is associated with
      cerebellar midline localization, and miR-182 is significantly overexpressed in
      metastatic MB as compared to non-metastatic tumors. Overexpression of miR-182 in
      non-SHH-MB increases and knockdown of miR-182 decreases cell migration in vitro.
      Xenografts overexpressing miR-182 invaded adjacent normal tissue and spread to
      the leptomeninges, phenotypically reminiscent of clinically highly aggressive
      large cell anaplastic MB. Hence, our study provides strong in vitro and in vivo
      evidence that miR-182 contributes to leptomeningeal metastatic dissemination in
      non-SHH-MB. We therefore reason that targeted inhibition of miR-182 may prevent
      leptomeningeal spread in patients with non-SHH-MB.

PMID- 22134539
TI  - Mice with asthma are more resistant to influenza virus infection and NK cells
      activated by the induction of asthma have potentially protective effects.
AB  - PURPOSE: This study was conducted in order to investigate whether the virulence
      of the influenza virus infection is affected by asthma in mice. METHODS: Mice
      with asthma or control mice were infected with influenza virus. The survival
      rate, body weight, virus titer, cytokine profile, and cell infiltration in
      bronchoalveolar lavage fluid (BALF) were measured. The NK cell cytotoxicity was
      determined by a co-culture system with YAC-1 cells, and the effects of NK cells
      were observed by depletion of NK cells using anti-asialoGM1 serum. The virus
      specific CD8(+) T cell killing assay was also performed. RESULTS: When asthmatic
      or control mice were infected with non- and sub-lethal doses of influenza virus,
      the asthmatic mice were more resistant to the virus than control mice with regard
      to the survival rate, the remission of body weight loss, and the virus burden.
      Anti-viral cytokines and the NK cell number were increased in the BALF of
      asthmatic mice before the infection. The NK cell cytotoxicity in the asthmatic
      mice was significantly enhanced compared to that in control mice, and the
      depletion of NK cells in asthmatic mice was abrogated both the improved survival
      rate and the recovery of the body weight loss. The antigen-specific CD8(+) T cell
      killing activity in asthmatic mice was also significantly increased following the
      infection compared to that in control mice. CONCLUSION: NK cell activated by the
      induction of asthma and the subsequently activated antigen-specific CD8(+) T
      cells could promptly eliminate the viral-infected cells, thus leading to
      improvements in the morbidity and mortality of influenza virus infection.

PMID- 22134540
TI  - A phase II study of the combination of endocrine treatment and bortezomib in
      patients with endocrine-resistant metastatic breast cancer.
AB  - The majority of patients with hormone receptor-positive metastatic breast cancer
      die from disease progression despite different types of anti-hormonal treatments.
      Preclinical studies have indicated that resistance to anti-hormonal therapies may
      be the result of an activated NF-kappaB signalling pathway in breast cancer.
      Bortezomib is a proteasome inhibitor that blocks the NF-kappaB pathway. Recent
      pharmacodynamic and pharmaco-kinetic xenograft studies have shown that drug
      exposure may be a crucial factor for the efficacy of bortezomib in solid tumours.
      The aim was to investigate whether the addition of bortezomib to anti-hormonal
      therapy would result in regained antitumour activity in patients with progressive
      and measurable disease being treated with an endocrine agent. Clinical benefit
      was defined as patients obtaining stable disease, partial response or complete
      response after 2 cycles, lasting for at least another five weeks. Bortezomib was
      administered on days 1, 8, 15 and 22 of a 5-week regimen (1.6 mg/m2). Eight
      patients received an aromatase inhibitor and bortezomib, while one received
      tamoxifen and bortezomib. There were 3 grade 3 gastrointestinal toxicities.
      Median time to treatment failure was 69 days (range, 35-140). Two out of the 9
      patients had stable disease for more than 10 weeks. Despite an effective target
      inhibition, suggested in peripheral blood mononuclear cells and available tumour
      samples, no objective antitumour responses were observed. Addition of a
      proteasome inhibitor to anti-hormonal therapy resulted in a clinical benefit rate
      of 22% in a limited number of patients with endocrine resistant and progressive
      metastatic breast cancer. The demonstrated proteasome inhibition in tumour tissue
      provides evidence that the lack of clinical responses is not attributed to
      deficient drug exposure.

PMID- 22134541
TI  - Propionic acidemia: neonatal versus selective metabolic screening.
AB  - BACKGROUND: Whereas propionic acidemia (PA) is a target disease of newborn
      screening (NBS) in many countries, it is not in others. Data on the benefit of
      NBS for PA are sparse. STUDY DESIGN: Twenty PA patients diagnosed through NBS
      were compared to 35 patients diagnosed by selective metabolic screening (SMS)
      prompted by clinical findings, family history, or routine laboratory test
      results. Clinical and biochemical data of patients from 16 metabolic centers in
      Germany, Austria, and Switzerland were evaluated retrospectively. Additionally,
      assessment of the intelligent quotient (IQ) was performed. In a second step, the
      number of PA patients who have died within the past 20 years was estimated based
      on information provided by the participating metabolic centers. RESULTS: Patients
      diagnosed through NBS had neither a milder clinical course regarding the number
      of metabolic crises nor a better neurological outcome. Among NBS patients, 63%
      were already symptomatic at the time of diagnosis, and <10% of all patients
      remained asymptomatic. Among all PA patients, 76% were found to be at least
      mildly mentally retarded, with an IQ <69. IQ was negatively correlated with the
      number of metabolic decompensations, but not simply with the patients' age.
      Physical development was also impaired in the majority of patients. Mortality
      rates tended to be lower in NBS patients compared with patients diagnosed by SMS.
      CONCLUSION: Early diagnosis of PA through NBS seems to be associated with a lower
      mortality rate. However, no significant benefit could be shown for surviving
      patients with regard to their clinical course, including the number of metabolic
      crises, physical and neurocognitive development, and long-term complications.

PMID- 22134542
TI  - Glycosylation defects underlying fetal alcohol spectrum disorder: a novel
      pathogenetic model. "When the wine goes in, strange things come out" - S.T.
      Coleridge, The Piccolomini.
AB  - Fetal alcohol spectrum disorder (FASD) is an umbrella term used to describe the
      craniofacial dysmorphic features, malformations, and disturbances in growth,
      neurodevelopment and behavior occurring in individuals prenatally exposed to
      alcohol. Fetal alcohol syndrome (FAS) represents the severe end of this spectrum.
      Many pathophysiological mechanisms have hitherto been proposed to account for the
      disrupted growth and morphogenesis seen in FAS. These include impaired
      cholesterol-modification of the Sonic hedgehog morphogen, retinoic acid
      deficiency, lipoperoxidative damage due to alcohol-induced reactive oxygen
      species combined with reduced antioxidant defences, and malfunctioning cell
      adhesion molecules. In this report, we propose a completely novel concept
      regarding the pathogenesis of FAS. Based on our observation that transferrin
      isoelectric focusing (TIEF) - the most widely used screening tool for congenital
      disorders of glycosylation (CDG) - was transiently abnormal in a newborn with FAS
      and a confirmed maternal history of gestational alcohol abuse, we came to believe
      that FAS exemplifies a congenital disorder of glycosylation secondary to alcohol
      inflicted disruption of (N-linked) protein glycosylation. Various pieces of
      evidence were found in the literature to substantiate this hypothesis. This
      observation implies, among others, that one might need to consider the
      possibility of maternal alcohol consumption in newborns with transient
      glycosylation abnormalities. We also present an integrated pathophysiological
      model of FAS, which incorporates all existing theories mentioned above as well as
      our novel concept. This model highlights the pivotal role of disrupted isoprenoid
      metabolism in the origination of FAS.

PMID- 22134543
TI  - A time course assessment of changes in reactive oxygen species generation and
      antioxidant defense in hydroponically grown wheat in response to lead ions
      (Pb2+).
AB  - We examined the effect of Pb(2+) (8 and 40 mg l(-1)) on reactive oxygen species
      generation and alterations in antioxidant enzymes in hydroponically grown wheat
      at 24, 72, and 120 h after exposure. Pb(2+) toxicity was more pronounced on root
      growth, and it correlated with the greater Pb accumulation in roots. Pb exposure
      (40 mg l(-1)) enhanced superoxide anion, H(2)O(2), and MDA content in wheat roots
      by 1.9- to 2.2-folds, 56-255%, and 41-90%, respectively, over the control. Pb
      induced loss of membrane integrity was confirmed by the enhanced electrolyte
      leakage and in vivo histochemical localization. Activities of scavenging enzymes,
      superoxide dismutases and catalases, enhanced in Pb-treated wheat roots by 1.4-
      to 5.7-folds over that in the control. In contrast, the activities of ascorbate
      and guaiacol peroxidases and glutathione reductases decreased significantly,
      suggesting their non-involvement in detoxification process. The study concludes
      that Pb(2+)-induced oxidative damage in wheat roots involve greater H(2)O(2)
      accumulation and the deactivation of the related scavenging enzymes.

PMID- 22134544
TI  - Stem cells, morals and the courts.

PMID- 22134545
TI  - The return of the phage.

PMID- 22134546
TI  - Is there a neurobiology of the free will?

PMID- 22134547
TI  - Oxidative stress in the haematopoietic niche regulates the cellular immune
      response in Drosophila.
AB  - Oxidative stress induced by high levels of reactive oxygen species (ROS) is
      associated with the development of different pathological conditions, including
      cancers and autoimmune diseases. We analysed whether oxidatively challenged
      tissue can have systemic effects on the development of cellular immune responses
      using Drosophila as a model system. Indeed, the haematopoietic niche that
      normally maintains blood progenitors can sense oxidative stress and regulate the
      cellular immune response. Pathogen infection induces ROS in the niche cells,
      resulting in the secretion of an epidermal growth factor-like cytokine signal
      that leads to the differentiation of specialized cells involved in innate immune
      responses.

PMID- 22134548
TI  - A new proofreading mechanism for lesion bypass by DNA polymerase-lambda.
AB  - Replicative DNA polymerases (DNA pols) increase their fidelity by removing
      misincorporated nucleotides with their 3' -> 5' exonuclease activity. Exonuclease
      activity reduces translesion synthesis (TLS) efficiency and TLS DNA pols lack 3' 
      > 5' exonuclease activity. Here we show that physiological concentrations of
      pyrophosphate (PP(i)) activate the pyrophosphorolytic activity by DNA pol-lambda,
      allowing the preferential excision of the incorrectly incorporated A opposite a
      7,8-dihydro-8-oxoguanine lesion, or T opposite a 6-methyl-guanine, with respect
      to the correct C. This is the first example of an alternative proofreading
      mechanism used during TLS.

PMID- 22134549
TI  - Stem cell research, scientific freedom and the commodification concern.

PMID- 22134550
TI  - Expression of microbiota, Toll-like receptors, and their regulators in the small
      intestinal mucosa in celiac disease.
AB  - OBJECTIVES: Less than one-tenth of the carriers of the risk genes HLA-DQ2 or HLA
      DQ8 develop celiac disease, suggesting that other genetic and environmental
      factors are important in the pathogenesis. The role of gut microbiota has been
      addressed previously with inconsistent findings. Our aim was to evaluate
      microbiota, its receptors (Toll-like receptors [TLRs]), and regulators of the
      TLRs in the small intestinal mucosa in celiac disease. METHODS: Microbiota was
      analyzed by quantitative polymerase chain reaction (total bacteria and 10
      bacterial group- and species-specific primers) and gene expression of interleukin
      8 (IL-8), TLR2, TLR3, TLR4, TLR5, TLR9, and regulators of TLRs, Toll-interacting
      protein (TOLLIP), and single immunoglobulin IL-1R-related molecule, by relative
      quantitative reverse transcription-polymerase chain reaction in 10 children with
      celiac disease (untreated celiacs), 9 children with normal small intestinal
      mucosa (controls), and 6 adults with celiac disease with normal small intestinal
      mucosa after following a gluten-free diet (treated celiacs). RESULTS: Small
      intestinal microbiota was comparable among controls, untreated celiacs, and
      treated celiacs. Expression of IL-8 mRNA, a marker of intestinal inflammation,
      was significantly increased in untreated celiacs as compared with treated celiacs
      (P=0.002) and controls (P=0.001). Expression of TLR-2 mRNA was significantly
      decreased in untreated (P=0.001) and treated (P=0.03) celiacs, whereas expression
      of TLR-9 mRNA was increased in untreated celiacs (P=0.001) as compared with
      controls. Expression of TOLLIP mRNA was downregulated in untreated celiacs as
      compared with controls (P=0.02). CONCLUSIONS: Altered gene expression of TLR2,
      TLR9, and TOLLIP in small intestinal biopsies in celiac disease suggests that
      microbiota-associated factors may be important in the development of the disease.

PMID- 22134551
TI  - 15-year-old girl with metaplastic atrophic gastritis and enterochromaffin-like
      cell hyperplasia.

PMID- 22134552
TI  - Early animal models of rickets and proof of a nutritional deficiency hypothesis.
AB  - In the period between 1880 and 1930, the role of nutrition and nutritional
      deficiency as a cause of rickets was established based upon the results from 6
      animal models of rickets. This greatly prevalent condition (60%-90% in some
      locales) in children of the industrialized world was an important clinical
      research topic. What had to be reconciled was that rickets was associated with
      infections, crowding, and living in northern latitudes, and cod liver oil was
      observed to prevent or cure the disease. Several brilliant insights opened up a
      new pathway to discovery using animal models of rickets. Studies in lion cubs,
      dogs, and rats showed the importance of cod liver oil and an antirachitic
      substance later termed vitamin D. They showed that fats in the diet were
      required, that vitamin D had a secosteroid structure and was different from
      vitamin A, and that ultraviolet irradiation could prevent or cure rickets.
      Several of these experiments had elements of serendipity in that certain dietary
      components and the presence or absence of sunshine or ultraviolet irradiation
      could critically change the course of rickets. Nonetheless, at the end of these
      studies, a nutritional deficiency of vitamin D resulting from a poor diet or lack
      of adequate sunshine was firmly established as a cause of rickets.

PMID- 22134553
TI  - Slow growth:  do not forget the thyroid.

PMID- 22134554
TI  - Rectal tonsil.

PMID- 22134555
TI  - Whole grain cereals: functional components and health benefits.
AB  - Cereal-based food products have been the basis of the human diet since ancient
      times. Dietary guidelines all over the world are recommending the inclusion of
      whole grains because of the increasing evidence that whole grains and whole-grain
      based products have the ability to enhance health beyond the simple provision of
      energy and nutrients. In this review we will examine the main chemical components
      present in whole grains that may have health enhancing properties (dietary fiber,
      inulin, beta-glucan, resistant starch, carotenoids, phenolics, tocotrienols, and
      tocopherols) and the role that whole grains may play in disease prevention
      (cardiovascular diseases and strokes, hypertension, metabolic syndrome, type 2
      diabetes mellitus, obesity, as well as different forms of cancer). The knowledge
      derived from the functional properties of the different chemical components
      present in whole grains will aid in the formulation and development of new food
      products with health enhancing characteristics.

PMID- 22134557
TI  - Fractional laser resurfacing of acne scarring in patients with Fitzpatrick skin
      types IV-VI.

PMID- 22134558
TI  - Short-term and low-dose oral fluconazole treatment can cause Stevens-Johnson
      syndrome in HIV-negative patients.

PMID- 22134559
TI  - Safety of tumescent and laser-assisted liposuction: review of the literature.
AB  - BACKGROUND: Tumescent liposuction (TL) allows the removal of large volumes of fat
      with minimal blood loss or postoperative morbidity, excellent cosmesis, and a
      remarkable safety profile. OBJECTIVE: To review the literature on the safety of
      tumescent liposuction, liposuction under general anesthesia and laser-assisted
      liposuction. RESULTS: Aggregate safety data on liposuction under tumescent
      anesthesia reveals over 100,000 body areas treated with liposuction. There were
      no serious complications of death, emboli, hypovolemic shock, perforation of
      thorax or peritoneum, thrombophlebitis, seizures, or toxic reactions to drugs. In
      contrast, in the plastic surgery literature, liposuction under general anesthesia
      was associated with complications of deep venous thrombosis or pulmonary embolus,
      abdominal or other organ perforation, infection, and bleeding. Most recently,
      survey data in the European literature analyzed data showed 72 cases of severe
      complications from liposuction, including 23 deaths in a 5-year period from 1998
      to 2002. The most frequent complications were bacterial infections such as
      necrotizing fasciitis, gas gangrene, and different forms of sepsis. Further
      causes of lethal outcome were hemorrhages, perforation of abdominal viscera, and
      pulmonary embolism. CONCLUSION: Tumescent local anesthesia utilizing lidocaine
      with epinephrine allows the removal of large volumes of fat with minimal
      associated blood loss and postoperative morbidity.

PMID- 22134560
TI  - Polyacrylamide hydrogel differences: getting rid of the confusion.
AB  - Polymer hydrogels have been used for many years in European and Asian countries,
      and these products are often considered to be the same material in different
      packaging. This, however, is not the case. Performance and safety profiles depend
      on many factors including chemical and physical characteristics (including
      rheological properties), manufacturing process and control (cross linking,
      impurities, stability, etc.), injection technique, and interaction with
      surrounding tissues. Polyacrylamide hydrogel (PAAH) products, although often
      considered equal, have clear differences in composition, manufacturing, and
      injection technique as well as ability to interact with surrounding tissues,
      characteristics that determine the safety and effectiveness profiles of each of
      these gels.

PMID- 22134561
TI  - Self-reported treatment impressions and satisfaction of papulopustular rosacea
      patients treated with doxycycline, USP, 40 mg capsules.
AB  - OBJECTIVES: This survey program was designed to evaluate patients' experiences
      with doxycycline, USP, 40 mg capsules (30 mg immediate release, 10 mg delayed
      release beads, ORACEA(r); Galderma Laboratories, L.P.) as a treatment for the
      inflammatory lesions of rosacea and to provide patient-reported feedback to
      physicians. METHODS: This prospective, cross-sectional survey was implemented in
      January 2010. One thousand, two hundred and ninety-five physicians identified
      patients eligible for treatment with doxycycline, USP, 40 mg capsules and
      provided them with information about the program. Patients voluntarily
      participated by contacting a program coordinator or by enrolling online,
      providing consent, and responding to a series of questions prior to medication
      use and approximately four weeks post-treatment initiation. Surveys were
      completed through an automated interactive voice response system or a dedicated,
      secure website and included questions regarding patients' perceptions of when the
      treatment first started working, patients' symptom severity, interference of
      symptoms with work and social activities, and confidence in appearance. Patients
      were also asked about prior medication use, adjunct medication use, and treatment
      satisfaction. Reports of patient progress and responses to these survey questions
      were sent directly to each patient's treating physician within a few days of
      survey completion. Paired t-tests were used to evaluate the statistical
      significance of differences in symptom severity, interference and confidence
      ratings before and after treatment. RESULTS: Two thousand, eight hundred ninety
      eight patients enrolled in the survey program and completed the baseline survey.
      Of these, a total of 1,346 patients completed the baseline and four-week survey
      (mean age 50 years; 75% female). Most (58%) reported use of a prior prescription
      medication to treat rosacea. Over half the patients (52%) responded that the
      product began to work within two weeks of use. After four weeks of using
      doxycycline, USP, 40 mg capsules, patients felt that the severities of redness as
      well as bumps/blemishes were significantly reduced (P<.05). Patients also
      reported having more confidence with their skin's appearance (P<.05). In
      addition, with use of doxycycline, USP, 40 mg capsules, patients reported
      significant reductions in the interference of symptoms with work and social
      activities (P<.05). Satisfaction with doxycycline, USP, 40 mg capsules averaged
      6.8 on a scale of 1 (not at all satisfied) to 9 (very satisfied) for patients
      using only doxycycline, USP, 40 mg capsules; mean satisfaction was 6.7 for those
      using it with adjunct medication. Seven patients reported 11 adverse events
      during the program, including lack of efficacy, joint injury with fatigue,
      dizziness, back pain, bloating and constipation, increased facial redness and
      pimples, yeast infection, sore throat, increased bruising and worsening of
      rosacea. CONCLUSION: Satisfaction with doxycycline, USP, 40 mg capsules for the
      treatment of papulopustular rosacea was apparent from patient-rated measures of
      treatment impact. Patients with papulopustular rosacea reported improvement in
      symptoms, reductions in the interference of symptoms with life's activities and
      satisfaction with treatment with doxycycline, USP, 40 mg capsules.

PMID- 22134562
TI  - Safety and efficacy of clindamycin phosphate 1.2%-benzoyl peroxide 3% fixed-dose
      combination gel for the treatment of acne vulgaris: a phase 3, multicenter,
      randomized, double-blind, active- and vehicle-controlled study.
AB  - BACKGROUND: Topical fixed-combination therapy containing 1% clindamycin as 1.2%
      clindamycin phosphate (CLNP) and 3% benzoyl peroxide (BPO) is an effective
      treatment for acne vulgaris (acne). OBJECTIVES: To demonstrate that the
      combination of 1.2% CLNP with lower strength BPO (CLNP 1.2%-BPO 3%) in a gel
      formulation is superior to each individual ingredient, CLNP 1.2% and BPO 3%, and
      vehicle gel. METHODS: A total of 1,319 patients with acne, aged 12 years or
      older, were enrolled and randomized (1:1:1:1) to receive CLNP 1.2%-BPO 3%, CLNP
      1.2% gel, BPO 3% gel, or vehicle gel once-daily in a 12-week, multicenter, double
      blind, parallel-group, vehicle-controlled study. Subjects were evaluated at
      baseline, weeks 2, 4, 8, and 12 or early termination. Assessment of efficacy was
      evaluated using a six-point Investigator's Static Global Assessment (ISGA) and
      Subject's Global Assessment (SGA) of acne severity and lesion counts
      (inflammatory, non-inflammatory, and total). Safety assessments included skin
      tolerability and adverse events (AEs). RESULTS: A greater proportion of subjects
      who used CLNP 1.2%-BPO 3% gel (39%) had a two grade improvement in ISGA from
      baseline to week 12 compared with CLNP 1.2% (25%; P<0.001), BPO 3% (30%;
      P=0.016), and vehicle (18%; P<0.001). CLNP 1.2%- BPO 3% was superior to CLNP 1.2%
      and vehicle alone in the absolute reduction from baseline to week 12 in all three
      lesion types (P<0.001 all pair-wise comparisons). CLNP 1.2%-BPO 3% was superior
      to BPO 3% alone in the absolute reduction from baseline to week 12 in
      inflammatory (P=0.015) and total (P=0.032) lesion counts. The incidence of
      product-related AEs was low and similar in all study groups (1% with CLNP 1.2%
      BPO 3%, 2% with CLNP 1.2%, 2% with BPO 3%, and 2% with vehicle). Local
      tolerability assessments showed similar minimal changes from baseline to week 12
      in all study groups. CONCLUSION: CLNP 1.2%-BPO 3% gel provides superior efficacy
      to improve ISGA score and reduce inflammatory and total lesion counts compared
      with the individual active ingredients (CLNP 1.2% and BPO 3%) and vehicle, while
      maintaining a highly favorable safety and tolerability profile similar to BPO 3%
      alone.

PMID- 22134563
TI  - Treatment of mild-to-moderate chronic hand dermatitis with clobetasol propionate
      0.05% EF foam: results from an open-label study.
AB  - OBJECTIVE: To assess the safety and efficacy of clobetasol propionate 0.05%
      emulsion formulation (EF) foam in subjects with mild-to-moderate chronic hand
      dermatitis. METHODS: This was a single-center, open-label pilot study of 30
      adults with chronic hand dermatitis. Subjects were treated with clobetasol
      propionate 0.05% EF foam twice-daily and returned for assessment at day 8 and day
      15. The primary efficacy endpoint was the proportion of subjects who achieved
      treatment success, defined as improvement of >= 1 grade in their chronic hand
      dermatitis as per the Investigator's Static Global Assessment (ISGA) from
      baseline to day 15. Safety and quality-of-life measures were also assessed.
      RESULTS: A minimum 1-grade improvement in the ISGA was achieved by 96.7 percent
      (29/30) of subjects at day 15, with 80 percent (24/30) of subjects achieving a
      score of 0 (clear) or 1 (almost clear). Clobetasol propionate 0.05% EF foam
      appeared to be safe and well-tolerated, with only four subjects experiencing
      treatment-related adverse events. No pattern of adverse event occurrence or
      predisposition could be delineated from this study. CONCLUSION: Clobetasol
      propionate 0.05% EF foam appeared to be safe and effective for the treatment of
      chronic hand dermatitis.

PMID- 22134564
TI  - The role of inflammation and immunity in the pathogenesis of androgenetic
      alopecia.
AB  - BACKGROUND: Female pattern hair loss affects many women; its pathogenetic basis
      has been held to be similar to men with common baldness. OBJECTIVE: The objective
      of this study was to determine the role of immunity and inflammation in
      androgenetic alopecia in women and modulate therapy according to inflammatory and
      immunoreactant profiles. MATERIALS AND METHODS: 52 women with androgenetic
      alopecia (AA) underwent scalp biopsies for routine light microscopic assessment
      and direct immunofluroescent studies. In 18 patients, serologic assessment for
      antibodies to androgen receptor, estrogen receptor and cytokeratin 15 was
      conducted. RESULTS: A lymphocytic folliculitis targeting the bulge epithelium was
      observed in many cases. Thirty-three of 52 female patients had significant
      deposits of IgM within the epidermal basement membrane zone typically accompanied
      by components of complement activation. The severity of changes light
      microscopically were more apparent in the positive immunoreactant group. Biopsies
      from men with androgenetic alopecia showed a similar pattern of inflammation and
      immunoreactant deposition. Serologic assessment for antibodies to androgen
      receptor, estrogen receptor or cytokeratin 15 were negative. Combined modality
      therapy with minocycline and topical steroids along with red light produced
      consistent good results in the positive immunoreactant group compared to the
      negative immunoreactant group. CONCLUSION: A lymphocytic microfolliculitis
      targeting the bulge epithelium along with deposits of epithelial basement
      membrane zone immunoreactants are frequent findings in androgenetic alopecia and
      could point toward an immunologically driven trigger. Cases showing a positive
      immunoreactant profile respond well to combined modality therapy compared to
      those with a negative result.

PMID- 22134565
TI  - Is chronic cutaneous discoid lupus protective against severe renal disease in
      patients with systemic lupus erythematosus?
AB  - OBJECTIVE: The aim was to assess the level of systemic involvement and character
      of renal disease in patients with chronic cutaneous lupus erythematosus of the
      discoid lupus variety (hereafter referred to as 'discoid lupus') and features of
      systemic lupus erythematosus (SLE). Clinical confusion with other types of
      cutaneous lupus erythematosus complicates interpretation of some previously
      reported studies. METHODS: Over three years, sixteen patients met the diagnostic
      criteria of discoid lupus, positive anti-nuclear-antibody, and at least one
      extracutaneous manifestation. RESULTS: Most patients (14/16) were female, between
      26 to 66 years old. Arthritis was the most common extracutaneous manifestation
      followed by Raynaud's phenomenon. The anti-nuclear-antibody was speckled in ten
      patients with titers ranging from 1:40 to 1:1280 IU/mL. Elevated levels of double
      stranded-DNA in low titers were found in four patients, anti-Smith-antibody in
      four; anti-Sjogren-syndrome-A-antibody in seven, and anti-ribonucleoprotein
      antibody in seven. Renal function markers were transiently high in some patients
      but normalized over time. Hematuria and/or proteinuria were present at some time
      in seven patients. The highest BUN and creatinine levels were 42 mg/dL and 1.5
      mg/dL, respectively. One patient had membranous glomerulonephropathy class 5;
      however, discoid lupus developed well after the onset of renal disease during a
      time when renal function had returned to normal. CONCLUSION: Our observational
      data supports previous reports suggesting that patients with active discoid lupus
      rarely have progressive renal insufficiency. The mechanism for the development of
      discoid lupus may involve an immunologic mechanism that differs from that which
      produces severe organ involvement, especially advanced immune-complex-mediated
      renal disease. Patients with discoid lupus rarely have sustained high levels of
      antibodies to double-stranded-DNA. Discoid lupus appears to be a marker for a
      more benign lupus course. This clinical observation lays the groundwork for a
      larger prospective, longitudinal cohort study for further validation.

PMID- 22134566
TI  - Treatment of chronic urticaria with colchicine.
AB  - BACKGROUND: Chronic urticaria (CU) is a cutaneous disease that can be
      debilitating, difficult to treat, and sometimes life-threatening. Treatment with
      antihistamines is often ineffective. Immunosuppressants are second line therapy
      but can have significant side effects. Data is needed on effective therapies with
      safer profiles. OBJECTIVES: To determine the efficacy and side-effects of
      colchicine in patients with CU. METHODS: Patients were identified through
      retrospective chart reviews at the University of Utah from 2002-2007. We
      identified 36 patients with a diagnosis of chronic urticaria based on history,
      physical examination, and a skin biopsy. Length of treatment ranged from one
      month to 17 months. RESULTS: Subjective clinical responses to colchicine therapy
      reported as complete (n=15) or partial (n=5) were found in 56 percent of
      patients. The mean+/-SD duration of treatment was 7+/-6 months. Three patients
      (15%) who had resolution of urticaria stopped colchicine secondary to diarrhea
      and hematuria. Of the complete responders, nine individuals (60%) have remained
      symptom free and four individuals (27%) had recurrence after colchicine was
      stopped. LIMITATIONS: Short-term follow-up and retrospective study design.
      CONCLUSIONS: This retrospective study demonstrated that colchicine was an
      effective and well-tolerated treatment for patients unresponsive to
      antihistamines. The data supports the use of colchicine for CU patients and
      further controlled studies are warranted to better characterize the use of
      colchicine in patients with CU refractory to antihistamines.

PMID- 22134567
TI  - Drug hypersensitivity in the age of electronic medical records.
AB  - Cutaneous drug eruptions are a common adverse reaction to medication. Creation of
      a drug calendar that covers a two-week span prior to the onset of rash is useful
      to identify the culprit agent. However, the creation of a drug calendar is often
      labor intensive. We developed an electronic version of a drug calendar that has
      considerably increased the ease and efficiency of completing a dermatology
      consultation.

PMID- 22134568
TI  - A comparison of cryotherapy and imiquimod for treatment of actinic keratoses:
      lesion clearance, safety, and skin quality outcomes.
AB  - BACKGROUND: There is limited direct comparative data on imiquimod versus
      cryotherapy to treat actinic keratoses. OBJECTIVE: Compare lesion response
      through 12 months post-initial treatment. METHODS: Patients with >= 10 lesions on
      the face or scalp were randomized to cryotherapy (up to 10 lesions per session,
      up to 4 sessions, every 3 months) or imiquimod (3-times-per-week for 3-4 weeks,
      up to 2 courses) with repeat treatment depending on response. RESULTS: In 36
      patients assigned to cryotherapy and 35 to imiquimod, lesion complete response
      rates were 85.0 percent (306/360) and 66.9 percent (234/350) for cryotherapy and
      imiquimod, respectively (P<0.0002). For completely cleared lesions, global skin
      quality was excellent in 82 percent (250/306) versus 100 percent (234/234) for
      cryotherapy and imiquimod, respectively (P<0.0001). More cryotherapy than
      imiquimod patients had hypopigmentation (54.8% versus 24.0%, P=0.0197), as well
      as blister formation, redness/erythema, flaking/scaling/dryness, and
      scabbing/crusting (P<0.05). CONCLUSION: 12-month lesion complete clearance rate
      was higher with repeated cryotherapy, but cosmetic outcome was better with
      imiquimod.

PMID- 22134569
TI  - Comparison between 1% tretinoin peeling versus 70% glycolic acid peeling in the
      treatment of female patients with melasma.
AB  - Melasma is an irregular brownish pigmentation observed on the faces of young to
      middle-aged women, especially of Asian races, which may contribute to various
      emotional disturbances. Although not any favorable treatment being approved yet,
      one appropriate approach is peeling by glycolic acid 70% (GA 70%). Considering
      the efficiency of Tretinoin in lower concentrations as over-the-counter
      lightening agents, peelings with higher strength Tretinoin may effectively
      relieve the pigmentation (melasma) sooner than other topical therapies.
      OBJECTIVE: The main purpose was to compare the efficiency and complications of GA
      70% with Tretinoin 1% peeling. METHODS: A randomized, double-blinded clinical
      trial performed on 63 female patients with bilateral melasma. One facial side was
      treated by drug A (GA 70%) and the opposite side by agent B (Tretinoin 1%)
      peeling for four sessions with 2-week intervals. Descending changes in Melasma
      Area and Severity Index (MASI) scores, patients' discomfort and untoward
      complications following peeling all were evaluated and compared during the
      research period. RESULTS: The efficiency of Tretinoin 1% peelings in declining
      the MASI score (treatment of melasma) was similar to GA 70%, as well as the rare
      unwanted complications of them. However, the patients' discomfort following
      procedures as expressed by their own, was significantly lower with Tretinoin 1%
      compared to GA 70% peeling. The cases' satisfaction with the intervention was
      statistically similar to each other. Furthermore, we experienced almost the equal
      times of beginning the therapeutic responses in both groups.

PMID- 22134571
TI  - Evaluation of a prescription strength 4% hydroquinone/10% L-ascorbic acid
      treatment system for normal to oily skin.
AB  - INTRODUCTION: A 4% hydroquinone/10% L-ascorbic acid treatment system aims to
      treat early signs of photodamage in normal to oily skin and help prevent further
      photodamage. The system also contains vitamin E, witch hazel, aloe barbadensis
      leaf juice, penetration-enhancing ingredients, micronized zinc oxide, and
      octinoxate. METHODS: Patients with minimal or mild facial photodamage and
      hyperpigmentation, and normal to oily facial skin, used the treatment system for
      12 weeks. RESULTS: Of 34 females enrolled, 30 completed. Median scores for the
      overall integrated assessment of photodamage, overall intensity of pigmentation,
      fine lines and wrinkles, tactile roughness, and laxity were significantly
      improved at week 12 compared with baseline. Furthermore, >= 90 percent of
      patients considered their skin was smoother, softer, more evenly toned, and more
      radiant, and 100 percent were satisfied with the overall appearance of their
      skin. CONCLUSION: The treatment system can help to ameliorate early signs of
      photodamage in normal to oily skin.

PMID- 22134570
TI  - Rupatadine and levocetirizine in chronic idiopathic urticaria: a comparative
      study of efficacy and safety.
AB  - BACKGROUND: Chronic Idiopathic Urticaria is difficult to treat due to its
      persistent debilitating symptoms. New generation anti-histaminics are first line
      treatment for this condition. The aim of this study is to compare efficacy and
      safety of rupatadine and levocetirizine in chronic idiopathic urticaria. METHODS:
      A randomized, single blinded, single-centred, parallel group outdoor based
      clinical study was conducted in 70 patients of CIU to compare the two drugs.
      After initial clinical assessment and baseline investigations, rupatadine was
      prescribed to 35 patients and levocetirizine to another 35 patients for 4 weeks.
      At follow-up, the patients were re-evaluated and then compared using different
      statistical tools. Main outcome measures were DC eosinophil, Absolute Eosinophil
      Count (AEC), serum IgE, Total Symptom Score, Aerius Quality of Life Questionnaire
      score, and Global efficacy score. RESULTS: Rupatadine significantly improved
      patients' clinical condition including symptom score from baseline to day 28. In
      rupatadine group, there was 27.9 percent decrease (P=0.027) in DC eosinophil,
      35.6 percent decrease (P=0.036) in AEC, 15.3 percent decrease (P=0.024) in serum
      IgE, 28.2 percent decrease (P=0.02) in Total Symptom Scoring, and 27.3 percent
      decrease (P=0.006) in Aerius Quality of Life Questionnaire score. Global efficacy
      score of rupatadine was found to be significantly greater (P=0.009) than
      levocetirizine. The overall incidence of adverse drug reactions was also found to
      be less in rupatadine group. CONCLUSION: Rupatadine is a better choice in CIU in
      comparison to levocetirizine due to better efficacy and safety profile.

PMID- 22134572
TI  - Erythema multiforme-like drug reaction to sorafenib.
AB  - The authors present a case of erythema multiforme-like drug reaction to the
      multikinase inhibitor sorafenib. While considered targeted therapy, multikinase
      inhibitors have been demonstrated to have various cutaneous effects. It is
      important to distinguish allergic reactions from adverse side effects as the
      latter may permit cautious re-challenge with medications that can potentially
      prolong survival in patients with advanced or metastatic disease.

PMID- 22134573
TI  - Treatment of recalcitrant generalized granuloma annulare with adalimumab.
AB  - Granuloma annulare is a benign, usually self-limited, dermatosis of unknown
      cause. Generalized lesions occur in approximately 15 percent of patients with GA
      and may cause mild to severe cosmetic disfigurement. The treatment of generalized
      granuloma annulare can be challenging. We report the case of a 36-year-old male
      patient with a generalized granuloma annulare who had failed topical and systemic
      glucocorticoids, systemic retinoids, dapsone, minocycline, PUVA therapy, and
      hydroxicloroquine and was successfully treated with adalimumab, an anti-TNF-alpha
      monoclonal antibody. Adalimumab may be an additional option in the treatment of
      recalcitrant forms of granuloma annulare.

PMID- 22134574
TI  - Vesiculobullous variant of adult T-cell leukemia/lymphoma in a Caribbean Emigre.
AB  - Adult T-cell leukemia/lymphoma (ATLL) results from human T-cell lymphotropic
      virus (HTLV) type I infection and may present as a diverse array of cutaneous
      findings. Often these clinical manifestations are non-specific and overlap
      significantly with cutaneous T-cell lymphoma (CTCL). However, it is exceedingly
      rare for a patient suffering from ATLL to develop vesicular or bullous pathology
      and only a handful of such cases have been reported in the literature. The
      authors describe a patient of Jamaican descent afflicted with ATLL who developed
      an impressive vesiculobullous eruption. This case provides further support of the
      near complete clinical overlap between ATLL and CTCL. Patients from HTLV endemic
      areas with consistent clinical manifestations should have viral serologies drawn
      as the treatment and prognosis of ATLL and CTCL differ greatly.

PMID- 22134575
TI  - Manifestations and treatment of cutaneous lupus erythematosus (Part II of II).

PMID- 22134576
TI  - A life changing experience and its impact on my professional development as a
      genetic counsellor.

PMID- 22134577
TI  - Uncomfortably content: my journey back to school.

PMID- 22134578
TI  - A serendipitous invitation.

PMID- 22134579
TI  - Diagnosis of fragile X syndrome: a qualitative study of African American
      families.
AB  - Fragile X syndrome (FXS) is an inherited genetic condition with critical
      consequences to the proband and family members at all levels in the generations.
      Although evidence demonstrates that the rates of diagnosis for FXS are the same
      in all racial groups, age of diagnosis in African American children has been
      reported to occur later than in Caucasian children. Additionally, African
      American families are seriously under-represented in existing FXS research
      studies. As such, it is important to understand the possible disparities in the
      underlying factors to receiving a diagnosis in African American families with
      FXS. Herein, a qualitative approach was adopted to describe the overall FXS
      diagnosis experiences (pre-diagnosis, diagnosis, and post-diagnosis stages) of a
      convenience sample of 10 African American mothers. We identified three major
      findings among our participants: (1) FXS testing is not ordered immediately once
      a parent expresses concerns of developmental delays to the pediatricians, (2) the
      diagnosis is sometimes delivered in an insensitive manner with information often
      being outdated and unbalanced towards negative aspects, (3) communication issues
      among family members exists once the diagnosis is discovered. Although these
      qualitative data may not be representative of the whole group, these findings
      have significant implications for genetic counseling and our understanding in
      providing support and advocacy for African American families with FXS.

PMID- 22134581
TI  - Improving the balance of carrier mobilities of host-guest solid-state light
      emitting electrochemical cells.
AB  - We report efficient host-guest solid-state light-emitting electrochemical cells
      (LECs) utilizing a cationic terfluorene derivative as the host and a red-emitting
      cationic transition metal complex as the guest. Carrier trapping induced by the
      energy offset in the lowest unoccupied molecular orbital (LUMO) levels between
      the host and the guest impedes electron transport in the host-guest films and
      thus improves the balance of carrier mobilities of the host films intrinsically
      exhibiting electron preferred transporting characteristics. Photoluminescence
      measurements show efficient energy transfer in this host-guest system and thus
      ensure predominant guest emission at low guest concentrations, rendering
      significantly reduced self-quenching of guest molecules. EL measurements show
      that the peak EQE (power efficiency) of the host-guest LECs reaches 3.62% (7.36
      lm W(-1)), which approaches the upper limit that one would expect from the
      photoluminescence quantum yield of the emissive layer (~0.2) and an optical out
      coupling efficiency of ~20% and consequently indicates superior balance of
      carrier mobilities in such a host-guest emissive layer. These results are among
      the highest reported for red-emitting LECs and thus confirm that in addition to
      reducing self-quenching of guest molecules, the strategy of utilizing a carrier
      transporting host doped with a proper carrier trapping guest would improve
      balance of carrier mobilities in the host-guest emissive layer, offering an
      effective approach for optimizing device efficiencies of LECs.

PMID- 22134580
TI  - Essential elements of genetic cancer risk assessment, counseling, and testing:
      updated recommendations of the National Society of Genetic Counselors.
AB  - Updated from their original publication in 2004, these cancer genetic counseling
      recommendations describe the medical, psychosocial, and ethical ramifications of
      counseling at-risk individuals through genetic cancer risk assessment with or
      without genetic testing. They were developed by members of the Practice Issues
      Subcommittee of the National Society of Genetic Counselors Familial Cancer Risk
      Counseling Special Interest Group. The information contained in this document is
      derived from extensive review of the current literature on cancer genetic risk
      assessment and counseling as well as the personal expertise of genetic counselors
      specializing in cancer genetics. The recommendations are intended to provide
      information about the process of genetic counseling and risk assessment for
      hereditary cancer disorders rather than specific information about individual
      syndromes. Essential components include the intake, cancer risk assessment,
      genetic testing for an inherited cancer syndrome, informed consent, disclosure of
      genetic test results, and psychosocial assessment. These recommendations should
      not be construed as dictating an exclusive course of management, nor does use of
      such recommendations guarantee a particular outcome. These recommendations do not
      displace a health care provider's professional judgment based on the clinical
      circumstances of a client.

PMID- 22134582
TI  - PD-sauvagine: a novel sauvagine/corticotropin releasing factor analogue from the
      skin secretion of the Mexican giant leaf frog, Pachymedusa dacnicolor.
AB  - Sauvagine is a potent and broad-spectrum biologically active peptide of 40 amino
      acid residues originally isolated from the skin of the South American frog,
      Phyllomedusa sauvagei. Since its discovery, no additional sauvagine structures
      have been reported. Following the discovery of sauvagine, peptides with similar
      primary structures/activities were identified in mammalian brain [corticotropin
      releasing factor (CRF) and urocortin]. Here, we report the identification of a
      second sauvagine from the Mexican giant leaf frog, Pachymedusa dacnicolor, which
      displays primary structural features of both sauvagine and CRF. A cDNA encoding
      the peptide precursor was "shotgun" cloned from a cDNA library constructed from
      lyophilised skin secretion by 3'- and 5'-RACE reactions. From this, the primary
      structure of a 38-mer peptide was deduced and this was located in reverse phase
      HPLC fractions of skin secretion and both its mass and structure were confirmed
      by mass spectrometry. The biological activities of synthetic replicates of PD
      sauvagine and sauvagine were compared using two different mammalian smooth muscle
      preparations and the novel peptide was found to be more potent in both.
      Bioinformatic analyses of PD-sauvagine revealed that it shared different regional
      sequence identities with both sauvagine and CRF.

PMID- 22134583
TI  - Membrane-destabilizing activity of pH-responsive cationic lysine-based
      surfactants: role of charge position and alkyl chain length.
AB  - Many strategies for treating diseases require the delivery of drugs into the cell
      cytoplasm following internalization within endosomal vesicles. Thus, compounds
      triggered by low pH to disrupt membranes and release endosomal contents into the
      cytosol are of particular interest. Here, we report novel cationic lysine-based
      surfactants (hydrochloride salts of N(epsilon)- and N(alpha)-acyl lysine methyl
      ester) that differ in the position of the positive charge and the length of the
      alkyl chain. Amino acid-based surfactants could be promising novel biomaterials
      in drug delivery systems, given their biocompatible properties and low cytotoxic
      potential. We examined their ability to disrupt the cell membrane in a range of
      pH values, concentrations and incubation times, using a standard hemolysis assay
      as a model of endosomal membranes. Furthermore, we addressed the mechanism of
      surfactant-mediated membrane destabilization, including the effects of each
      surfactant on erythrocyte morphology as a function of pH. We found that only
      surfactants with the positive charge on the alpha-amino group of lysine showed pH
      sensitive hemolytic activity and improved kinetics within the endosomal pH range,
      indicating that the positive charge position is critical for pH-responsive
      behavior. Moreover, our results showed that an increase in the alkyl chain length
      from 14 to 16 carbon atoms was associated with a lower ability to disrupt cell
      membranes. Knowledge on modulating surfactant-lipid bilayer interactions may help
      us to develop more efficient biocompatible amino acid-based drug delivery
      devices.

PMID- 22134584
TI  - Supramolecular light harvesting antennas to enhance absorption cross-section in
      dye-sensitized solar cells.
AB  - Doping a zinc porphyrin based-sensitizer with antenna molecules, axially held by
      metallo-supramolecular interactions, enhances the light-harvesting efficiency and
      the overall photo-conversion efficiency of the solar cells by about 30%.

PMID- 22134585
TI  - Uveal metastatic disease: current and new treatment options (review).
AB  - Choroidal metastasis represents the most common form of intraocular malignancies.
      It may occur in up to 10% of patients with systemic metastasis with almost half
      of the patients developing central nervous system disease. The most common
      primary sites of ocular metastasis are breast cancer in women and lung cancer in
      men. In most cases, these lesions tend to be asymptomatic and are not evaluated
      by an ophthalmologist. The diagnosis is generally made by the history of present
      or prior malignancies and an ophthalmological examination with slit-lamp
      biomicroscopy and indirect ophthalmoscopy. As with other malignancies, management
      may vary with each patient. Small tumors, that do not compromise the vision and
      that have responded previously to systemic treatment, may be closely observed.
      For larger lesions and for symptomatic ones, external beam radiation offers an
      excellent alternative to save the eye and stabilize vision. Bevacizumab
      (Avastin), a potent monoclonal antibody that has also been employed for the
      treatment of ocular vaso-proliferative diseases, has been used in the treatment
      of choroidal metastasis and has shown promising results.

PMID- 22134586
TI  - The island of ischaemia: submacular choroidal nonperfusion in giant cell
      arteritis.

PMID- 22134588
TI  - Five-year follow-up after anterior iris-fixated intraocular lens implantation in
      phakic eyes to correct high myopia.
AB  - PURPOSE: To evaluate the 5-year follow-up of safety, efficacy, predictability,
      stability, and complications of anterior iris-fixated phakic intraocular lens
      (pIOL) implantation to correct high myopia, and patients' satisfaction after
      implantation. DESIGN: Prospective, nonrandomized, and comparative (self
      controlled) trial. METHODS: A prospective clinical trial of 84 eyes of 43
      patients with high myopia was conducted. Uncorrected visual acuity (UCVA), best
      spectacle-corrected visual acuity (BSCVA), refraction, endothelial cell count,
      intraocular pressure (IOP), anterior chamber depth, slit lamp biomicroscopy, and
      indirect ophthalmoscope were measured preoperatively and postoperatively.
      RESULTS: At the 5-year follow-up, UCVA was significantly improved, with 85.7% of
      eyes reaching 20/25 or better. No eyes experienced a loss in BSCVA, and 71.4%
      gained one or more lines of their preoperative BSCVA. There was a significant
      reduction in spherical errors in all patients after operation. Loss of
      endothelial cells was observed 3 years after operation and no more loss was
      observed 4 years after operation in statistical analysis. No increase in IOP was
      observed 5 years after operation in statistical analysis. No intraoperative
      complications were observed in this study. However, pigment precipitates of
      varying intensities on the lens optic were noted in all patients 1 day after
      operation, and only five eyes were observed to have the pigment residual five
      years after operation. CONCLUSION: At the 5-year follow-up, the implantation of
      the anterior iris-fixated pIOL was proved to be effective, predictable and
      capable of reversibility to correct high myopia in phakic eyes. It was a safety
      addition to the laser refractive surgery. However, longer follow-up with larger
      numbers of patients is still necessary to evaluate long-term complications.

PMID- 22134589
TI  - An increase in intraocular pressure after intravitreal steroid injection
      facilitates reduction of macular edema.

PMID- 22134590
TI  - Alternative diagnoses with ectopia lentis.

PMID- 22134591
TI  - MRSA: why have we got it and can we do anything about it?
AB  - MRSA, first identified in 1960, became a major cause of healthcare-associated
      infection with the emergence of epidemic strains EMRSA 15 and 16 in the 1990 s.
      MRSA bacteraemia surveillance in England showed a peak of 7700 in 2003-2004. A
      target was set to halve MRSA bacteraemias by 2008 backed by a central improvement
      programme for infection prevention and control. Healthcare-associated infection
      is a patient safety issue with joint responsibility between: clinicians
      responsible for patient care; managers responsible for the organisation of
      services; and the government/Department of Health responsible for national
      strategy, prioritisation and performance management, together with introducing a
      statutory Code of Practice. By 2011, the number of MRSA bacteraemias had reduced
      by 80% to 1481. The key drivers of improvement were management responsibility,
      enhanced surveillance, adherence to clinical protocols and care bundles for
      invasive procedures, hand hygiene and environmental cleaning, and improved
      isolation procedures and antibiotic stewardship. The target has been translated
      into an ongoing MRSA objective, and further control of MRSA is supported by a
      screening programme aimed at all relevant hospital admissions. Sustaining the
      reduction will depend upon joint responsibility between management maintaining
      compliance assurance with policies and individual clinicians keeping it as a
      priority in patient safety.

PMID- 22134592
TI  - Contact lens-related microbial keratitis: how have epidemiology and genetics
      helped us with pathogenesis and prophylaxis.
AB  - Contact lens wear is a common predisposing factor in microbial keratitis and is
      one of the two preventable risk factors for corneal infection in a working age
      population. Our understanding of the prevention and prophylaxis of contact lens
      related corneal infection is informed by recent epidemiological studies
      describing the incidence of and risk factors for the disease, the effect of
      causative organism on disease severity, and an appreciation of individual immune
      profiles in susceptibility to and severity of the disease. Although contemporary
      contact lenses have not reduced the overall incidence of keratitis, a reduction
      in morbidity may be achievable through recognition of appropriate risk factors in
      severe disease, including avoiding delays in presenting for appropriate
      treatment, and attention to storage case hygiene practise. Severe keratitis is
      most commonly associated with an environmental causative organism, and daily
      disposable lenses are associated with less severe disease. Pseudomonas aeruginosa
      remains the commonest cause of contact lens-related corneal infection probably
      because of its unique virulence characteristics and ability to survive in the
      contact lens/storage case/ocular environment. In two recent outbreaks of contact
      lens-related infections, there has been a strong association demonstrated with
      particular contact lens solutions. Since the recall of these specific contact
      lens solutions, the rate of Acanthamoeba keratitis has remained above the
      expected baseline, indicating unidentified risk factors that may include
      environmental exposures. Individual differences in susceptibility to microbial
      keratitis may be partly explained by differences in single-nucleotide
      polymorphisms in certain cytokine genes, particularly those with a proven
      protective role in corneal infection.

PMID- 22134595
TI  - 'Non-steroidal drug-induced glaucoma' by MR Razeghinejad, MJ Pro and LJ Katz.

PMID- 22134594
TI  - Association of human papilloma virus with pterygia and ocular-surface squamous
      neoplasia.
AB  - There are more microorganisms that colonize the human body than resident cells;
      some are commensal whereas others are pathogenic. Pathogenic microorganisms are
      sensed by the innate or adaptive immune system, an immune response is initiated,
      and the infection is often cleared. Some microorganisms have developed strategies
      to evade immune defenses, ensuring their long-term survival with potentially
      devastating consequences for the host. Approximately 18% of all cancers can be
      attributed to infective agents; the most common being Helicobacter pylori, Human
      papilloma virus (HPV) and Hepatitis B and C virus in causing stomach, cervical
      and liver carcinoma, respectively. This review focuses on whether HPV infection
      is necessary for initiating pterygia, a common benign condition and ocular
      surface squamous neoplasia (OSSN), a rare disease with metastatic potential. The
      search engine PubMed was used to identify articles from the literature related to
      HPV and pterygium or conjunctival neoplasia. From 34 investigations that studied
      HPV in pterygia and OSSN, a prevalence rate of 18.6% (136/731) and 33.8%
      (144/426), respectively, was recorded. The variation in HPV prevalence (0-100%)
      for both disease groups may have arisen from study-design faults and the
      techniques used to identify the virus. Overall, the data suggest that HPV is not
      necessary for initiating either condition but may be a co-factor in susceptible
      hosts. Currently, over 60 million people worldwide have been immunized with HPV
      vaccines, but any effect on pterygium and OSSN development may not be known for
      some time as these lesions can evolve over decades or occur in older individuals.

PMID- 22134596
TI  - Importance of vision screening in children regardless of socioeconomic status.

PMID- 22134597
TI  - Spectral- and time-domain optical coherence tomography measurements of macular
      thickness in normal eyes and in eyes with diabetic macular edema.
AB  - PURPOSE: To report macular thickness values in normal eyes and eyes with diabetic
      macular edema (DME) using time-domain (TD) and spectral-domain (SD) optical
      coherence tomography (OCT), and to derive a conversion equation. METHODS: The
      index study was a prospective investigation conducted on 80 eyes from 40 normal
      subjects and 130 eyes from 118 patients with DME seen in our clinic. Retinal
      thickness values from the central 1 mm of the macula and surrounding four ETDRS
      subfields were acquired using TD-OCT (Stratus OCT) and SD-OCT (SPECTRALIS
      HRA+OCT). Measurements of the central (C) subfield from both devices were used to
      derive a conversion equation. The equation was used to predict SD-OCT values
      using measurements from TD-OCT. Agreement between predicted and actual SD-OCT
      measurements was assessed. RESULTS: In normal eyes, the mean difference between
      TD-OCT and SD-OCT measurements of the C subfield was 76 MUm (CI(95)=74 and 77,
      respectively). The conversion equation, y=1.029x+72.49, was derived. In eyes with
      DME, using the equation, SPECTRALIS-predicted values were 5% higher than actual
      measurements, with 95% of predicted values falling within 9% of the actual
      measurements. Relocating SD-OCT grids to match the location on TD-OCT resulted in
      predicted values falling within 7% of actual measurements. CONCLUSIONS: The
      percent difference between actual thickness measurements from SPECTRALIS and
      predicted thickness measurements, using the conversion equation, was within
      reported limits of repeatability of Stratus in eyes with DME. Our equation may
      help correlate OCT values from both devices in standard care and clinical trials
      for DME.

PMID- 22134598
TI  - Endophthalmitis following open-globe injuries.
AB  - The incidence of traumatic endophthalmitis may be decreasing due to earlier wound
      closure and prompt initiation of antibiotics. Risk factors for endophthalmitis
      include retained intraocular foreign body, rural setting of injury, disruption of
      the crystalline lens, and a delay in primary wound closure. The microbiology in
      the post-traumatic setting includes a higher frequency of virulent organisms such
      as Bacillus species. Recognizing early clinical signs of endophthalmitis,
      including pain, hypopyon, vitritis, or retinal periphlebitis may prompt early
      treatment with intravitreal antibiotics. Prophylaxis of endophthalmitis in high
      risk open-globe injuries may include systemic broad-spectrum antibiotics, topical
      antibiotics, and intravitreal antibiotics to cover both Gram-positive and Gram
      negative bacteria. For clinically diagnosed post-traumatic endophthalmitis,
      intravitreal vancomycin, and ceftazidime are routinely used. Concurrent retinal
      detachment with endophthalmitis can be successfully managed with vitrectomy and
      use of intravitreal antibiotics along with a long acting gas or silicone oil
      tamponade. Endophthalmitis is a visually significant complication of open-globe
      injuries but early wound closure as well as comprehensive prophylactic antibiotic
      treatment at the time of injury repair may improve visual acuity outcomes.

PMID- 22134600
TI  - Effect of CIDR(r) on 4-day-service-rate, pregnancy rate and vaginal irritation in
      dairy heifers.
AB  - OBJECTIVE: The objective of this study was to compare reproductive performance
      parameters for two protocols for estrus synchronization in dairy heifers in
      Germany. MATERIAL AND METHODS: In the CIDR group (n=93) all heifers received a
      controlled intravaginal progesterone releasing insert (Eazi-BreedTM CIDR(r);
      Pfizer Pharma GmbH; containing 1,38g of progesterone) on day 0. On day 7 these
      cows were given prostaglandin F2alpha (PGF2alpha) analogue cloprostenol
      (Estrumate(r), Intervet Deutschland GmbH, 0.5mg per animal i.m.), and the CIDR(r)
      insert was removed. Any mucus attached to the insert was scored on a 4-point
      scale: 0=no mucus; 1=clear; 2=bloody; 3=yellow/cloudy mucus. In the PG group
      (n=98) all heifers were given PGF2alpha analogue cloprostenol on day 7. Between
      day 8 and 11 heat detection was conducted twice daily for 30 minutes. All heifers
      in estrus were bred by artificial insemination (AI) and pregnancy was diagnosed
      40 days after AI by transrectal palpation. RESULTS: In the CIDR group the 4-day
      service rate was 91.4%, in the PG group 70.4% (p<0.05). More heifers in the CIDR
      group were pregnant than in the PGF2alpha protocol (76.3 vs. 56.1%,p<0.05). Mucus
      scores of 2 and 3 indicative of vaginal irritation were observed in 91.9% of the
      CIDR group but did not affect the pregnancy outcome (OR = 0.652, CI95 =0.235
      1.810; p=0.411). CONCLUSION: In conclusion, the CIDR protocol improved
      reproductive parameters of dairy heifers compared with a PGF2alpha protocol.
      Mucus after removal of the CIDR(r) insert did not affect pregnancy rates.

PMID- 22134599
TI  - Estimating biodiversity of fungi in activated sludge communities using culture
      independent methods.
AB  - Fungal diversity of communities in several activated sludge plants treating
      different influent wastes was determined by comparative sequence analyses of
      their 18S rRNA genes. Methods for DNA extraction and choice of primers for PCR
      amplification were both optimised using denaturing gradient gel electrophoresis
      profile patterns. Phylogenetic analysis revealed that the levels of fungal
      biodiversity in some communities, like those treating paper pulp wastes, were
      low, and most of the fungi detected in all communities examined were novel
      uncultured representatives of the major fungal subdivisions, in particular, the
      newly described clade Cryptomycota. The fungal populations in activated sludge
      revealed by these culture-independent methods were markedly different to those
      based on culture-dependent data. Members of the genera Penicillium, Cladosporium,
      Aspergillus and Mucor, which have been commonly identified in mixed liquor, were
      not identified in any of these plant communities. Non-fungal eukaryotic 18S rRNA
      genes were also amplified with the primer sets used. This is the first report
      where culture-independent methods have been applied to flocculated activated
      sludge biomass samples to estimate fungal community composition and, as expected,
      the data obtained gave a markedly different view of their population biodiversity
      compared to that based on culture-dependent methods.

PMID- 22134601
TI  - [Endoscopy in cattle].
AB  - Endoscopy in the field of buiatrics has gained growing importance in recent
      years. Parts of the upper respiratory and gastrointestinal tract, the urethra and
      urinary bladder, the abdomen and the teat are all accessible by means of
      endoscopy. The direct visualisation of inner or outer organ surfaces allows for
      rapid diagnosis and even prognosis of different pathological conditions. Flexible
      endoscopes of different dimensions are used for endoscopic examination of the
      upper respiratory tract. Examining this region, endoscopy is in some cases
      superior to other imaging techniques because of the direct visualization of
      surfaces and their pathological conditions and the possibility of collecting
      biopsies under visual control. The same is documented for diseases of the
      oesophagus. On the other hand, rumenoscopy is of experimental character so far.
      Urethrocystoscopy is mainly performed for diagnostic purposes with either
      flexible or rigid optics. Theloscopy represents the "gold standard" for surgical
      intervention in cases of disturbance of milk flow, since mucosal tissue can be
      removed under visual control. Therefore, this indication is one of the most
      important applications for endoscopy performed by practitioners. Another
      important field for the application of therapeutic endoscopy is the treatment of
      left displaced abomasum by repositioning and fixation to the abdominal wall under
      endoscopic control.

PMID- 22134602
TI  - [The use of ultrasonography for diagnosing the cause of colic in cows. A review].
AB  - Ultrasonography is a very useful technique for diagnosing the cause of colic in
      cows. It allows visualisation of abnormal reticular contour and occasionally of
      abnormal contractility in cows with reticuloperitonitis. In right-displaced
      abomasum, the dilated abomasum can be detected between the right abdominal wall
      and the liver. Fluid ingesta are seen ventrally and a gas cap of varying size
      dorsally. Dilated loops of small intestines that are almost always static are the
      main diagnostic criterion for ileus of the small intestine, but the cause of the
      ileus can only rarely be determined. Cholestasis can almost always be diagnosed
      by imaging a dilated biliary system. With obstruction at the level of the hepatic
      portal, only the intrahepatic biliary ducts are dilated, while a dilatation of
      the entire biliary tract, including the gallbladder, occurs in the case of an
      obstruction near the duodenal papilla. Urinary tract diseases cause colic in cows
      when concrement or inflammatory products become lodged in a ureter. The
      importance of ultrasonography in the diagnosis of diseases causing colic in cows
      varies. For example, with colic attributable to ileus of the small intestines,
      cholestasis or urinary tract disease, ultrasonography is a very useful diagnostic
      tool. On the other hand, for diagnosis of left or right displacement of the
      abomasum or caecal dilatation, ultrasonography is generally not required, but it
      is helpful in difficult cases to confirm or rule out a tentative diagnosis and to
      avoid an unnecessary exploratory laparotomy.

PMID- 22134603
TI  - [Ultrasonographic examination of the musculoskeletal system in cattle].
AB  - Ultrasound machines with 7.5 to 5.0MHz linear transducers are well suited for
      rapid and straightforward differentiation of soft tissue swelling in the
      musculoskeletal system of cattle; in proximal limb regions 3.5MHz convex scanners
      allow better imaging. The main indications for ultrasonography of the
      musculoskeletal system in cattle are suspected arthritis, tenosynovitis,
      bursitis, abscesses, haematomas, diagnosis of muscle and tendon lesions, and
      generally the evaluation of soft tissue swellings everywhere that cannot be
      diagnosed based on clinical examination. The examiner starts by obtaining a
      general overview of the affected region for orientation purposes. This is
      achieved by locating and identifying anatomical landmarks, thereafter one can
      search for pathological changes by examination of the region of interest in
      longitudinal and transverse planes from all sides. The ultrasonographic
      investigation should follow a standardised systematic protocol. Normal synovial
      cavities in cattle are difficult or impossible to visualize via ultrasonography
      because of the very small physiological amount of synovial fluid. Thus, effusion
      that is easily visualized usually indicates a pathological process like
      arthritis, tenosynovitis or bursitis. Ultrasonography provides accurate
      information about the location and size of lesions or fluid-filled cavities, the
      nature of the content and an exact measurement of the distance from
      pathologically altered structures to the skin surface. Targeted centesis of
      synovial or other cavities can be carried out after a preliminary
      ultrasonographic inspection. Characterization of the lesions and a thorough
      preoperative inspection of affected regions are of enormous benefit for planning
      surgery and treatment.

PMID- 22134604
TI  - [Clinical application of computed tomography in cattle].
AB  - Computed tomography involves the use of x-rays to produce cross-sectional images
      of body regions. It provides non-overlapping, two-dimensional images of all
      desired planes as well as three-dimensional reconstruction of regions of
      interest. There are few reports on the clinical use of computed tomography in
      farm animals. Its use in cattle is limited by high cost, the application of off
      label drugs and the need for general anaesthesia. In cattle computed tomography
      is indicated primarily for diseases of the head, e.g. dental diseases and otitis
      media, and neurological disorders. Less often it is used for diseases of the
      vertebrae and limbs. In valuable cattle, the results of computed tomography can
      be an important part of preoperative planning or be used to avoid unnecessary
      surgery when the prognosis is poor.

PMID- 22134605
TI  - [Ocular dermoids in a Simmental calf. A case report].

PMID- 22134606
TI  - [Radiographic examination of cattle].

PMID- 22134608
TI  - Is there a need for dedicated bone imaging in addition to 18F-FDG PET/CT imaging
      in pediatric sarcoma patients?
AB  - PURPOSE: Many children with sarcomas undergo whole body 2-deoxy-2-((18)F)fluoro-D
      glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and
      technetium methylene diphosphonate ((99)Tc-MDP) studies. It is unknown whether
      the combination of both tests results in more accurate detection of bone lesions
      than (18)F-FDG- PET/CT alone. METHODS: (99)Tc-MDP bone and (18)F-FDG PET/CT scans
      were each read by 2 "blinded" observers and then reviewed side-by-side by 3
      readers. Bone lesions were graded qualitatively on a 5-point scale (from benign
      to malignant). Clinical and imaging follow-up (n = 21) and bone biopsy results (n
      = 8) served as reference standard. RESULTS: A total of 39 paired (99)Tc-MDP and
      (18)F-FDG-PET/CT studies (cases) performed at a mean interval 4 +/- 7 days, were
      performed on 29 patients (mean age 12 +/- 5 y). Of these, 21 patients (72%) had
      bone sarcoma, whereas 8 patients (28%) had soft tissue sarcoma. By patient and
      case-based analysis, (18)F-FDG PET/CT had an accuracy of 100%. Tc-MDP had
      accuracies of 90% and 82% by patient and case-based analysis. The combined
      interpretation had an accuracy of 97%. CONCLUSIONS: In this study, (99)Tc-MDP
      bone imaging does not provide an added diagnostic value for bone involvement over
      (18)F-FDG-PET/CT.

PMID- 22134609
TI  - Pleuropulmonary blastoma as characteristic cause of pneumothorax.
AB  - BACKGROUND: Pleuropulmonary blastoma (PPB) is the most common lung neoplasms in
      childhood. Usually presents as recurrent respiratory infections and in some cases
      as pneumothorax. CASE REPORT: We report the case of a 2-year-old patient that was
      diagnosed with PPB, that first manifested as recurrent pneumothorax. Three chest
      computed tomography were necessary for the diagnosis. The first 2 tomographies
      showed no abnormalities suggestive of malignancy. The patient had a family
      history of both PPB and leukemia. Three years and a half after completion of
      treatment, the patient is in complete remission. CONCLUSIONS: PPB is an uncommon
      disease but is the most common pulmonary neoplasms in childhood. We must suspect
      it in patients with a suggestive family history and recurrent pneumothorax in the
      same location.

PMID- 22134610
TI  - Disseminated neuroendocrine carcinoma in a pediatric patient:  a rare case and
      diagnostic challenge.
AB  - A previously healthy 16-year-old female presented with 1-month history of fever,
      cough, extremity pain, left upper quadrant pain, and night sweats. Imaging
      studies revealed mediastinal lymphadenopathy, lung and liver masses, and bony
      lesions. Liver and bone marrow biopsies revealed small tumor cells with a high
      nuclear cytoplasmic ratio, stippled chromatin, and inconspicuous nucleoli
      surrounded by bands of collagen. Immunohistochemically, the tumor cells were
      positive for epithelial (epithelial membrane antigen and cytokeratin AE1/AE3) and
      neuroendocrine markers (chromogranin and synaptophysin), and negative for other
      antigens tested, including vimentin, desmin, CD99, and WT-1. The morphologic
      features and immunohistochemical profile was consistent with neuroendocrine
      carcinoma. Despite several chemotherapeutic regimens, the patient had progressive
      disease and enrolled in a phase 1 trial. Thorough histopathologic evaluation,
      including immunohistochemical stains is a crucial component for diagnosing this
      rare, aggressive tumor in children and adolescents.

PMID- 22134611
TI  - Gilbert syndrome increasing unconjugated hyperbilirubinemia in a child with
      hereditary spherocytosis.
AB  - Hemolytic anemia usually gives rise to only a modest elevation of serum
      bilirubin. Unconjugated hyperbilirubinemia of an extreme degree should raise
      suspicion of additional factors. We describe a 10-year-old child suffering from
      hereditary spherocytosis, who had unusually high levels of unconjugated serum
      bilirubin and was diagnosed to have Gilbert syndrome on the basis of genetic
      analysis.

PMID- 22134612
TI  - Improving circulatory disturbance in transient abnormal myelopoiesis.
AB  - Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) is
      characterized by circulating blast cells in the blood. TAM usually resolves
      spontaneously, but several studies have associated this condition with early
      death, focusing on the development of effective treatments. We report the case of
      a neonate with DS who had TAM and novel GATA1 mutation. Although the patient
      eventually died of hepatic failure, exchange blood transfusion and low-dose
      cytarabine treatment dramatically improved pulmonary hypertension and acute renal
      failure refractory to conventional therapy. Such a blast-reducing approach might
      be useful for improving circulatory disturbances in neonates with DS and TAM.

PMID- 22134613
TI  - Serum levels of mannose-binding lectin and the risk of infection in pediatric
      oncology patients with chemotherapy.
AB  - Morbidity and mortality due to infections remain serious problems in pediatric
      oncology patients receiving chemotherapy. Association of mannose-binding lectin
      (MBL) levels with an increased risk for infection in previous studies was
      contradictory. The aim of this study was to determine whether MBL deficiency is
      associated with the risk of infections in pediatric oncology patients. Before the
      start of chemotherapy a blood sample was taken from 75 patients with acute
      lymphoblastic leukemia and MBL serum concentration was measured using a
      commercially enzyme-linked immunosorbent assay kit. Twenty patients had
      concentrations under 1000 ug/L, defining MBL deficiency and the remaining 55
      patients had concentrations >1000 ug/L. Ten patients suffered from more than 1
      episode of severe infection. Sixty-five percent of patients with MBL below 1000
      ug/mL suffered from 2 or more episodes of infections (3 of 16 individuals with 1
      severe infection; 10 of 16 with 2 and 3 of 16 with 3), in contrast to only 29 of
      55 (52%) patients with MBL above 1000 ug/mL (19 of 27 individuals with 1 severe
      infection and 10 of 27 with 2). The difference between 2 groups was significant
      (P<0.001). The results of this study indicate that low MBL serum levels (<1000
      ug/L) identify pediatric cancer patients at increased risk for infections.

PMID- 22134614
TI  - Acute upper GI bleed in a 4-year-old boy: a case of atypical Burkitts lymphoma in
      a 4-year-old.
AB  - Lymphomas have been seen in the pediatric population; more frequently in patients
      with H. Pylori, Celiac disease, and/or patients with congenital or acquired
      immune deficiencies. We report a case of a 4-year old male with an acute gastric
      intestinal bleed accompanied by a rare lymphoma.

PMID- 22134615
TI  - A case report of acute lymphoblastic leukemia with delayed-type hypersensitivity.

PMID- 22134616
TI  - Fulminant and fatal course of acute lymphoblastic leukemia due to lactic acidosis
      and suspected abdominal compartment syndrome.
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and
      its prognosis has considerably improved over the past 2 decades due to new
      therapeutic approaches. In some cases, however, it can develop very rapidly and
      cause possibly fatal complications. We report on the case of an 11-year-old boy
      with ALL, who rapidly developed severe lactic acidosis and abdominal compartment
      syndrome. He died of multiorgan failure only 5 days after diagnosis of ALL had
      been established. Autopsy revealed systemic leukemic infiltrations. We suppose
      that the mass of tumor cells induced a cascade of metabolic and endocrine
      reactions, which not only triggered the rapid progression of the disease but were
      also accountable for the lack of response to treatment. The pathophysiology of
      abdominal compartment syndrome as a rare and in our case ultimately fatal
      complication of ALL is described.

PMID- 22134617
TI  - Recurrent arterial thrombosis associated with the antithrombin basel variant and
      elevated lipoprotein(a) plasma level in an adolescent patient.
AB  - Both myocardial infarction and ischemic stroke are rare in the young. Yet a 15
      year-old male patient suffered a myocardial infarction and later an ischemic
      stroke despite uninterrupted antiplatelet therapy. His medical history involved
      the surgical correction of an incomplete atrioventricular canal defect at the age
      of 13 years. No cardiovascular risk factors other than elevated lipoprotein(a)
      level could be identified. His antithrombin (AT) activity was decreased and DNA
      sequence analysis revealed heterozygosity for AT Basel (p.Pro41Leu), a variant
      with impaired heparin binding. This report supports a possible additional
      pathophysiological role for AT Basel and elevated lipoprotein(a) level in
      arterial thrombogenesis.

PMID- 22134618
TI  - Total hip arthroplasty: to cement or not to cement the acetabular socket? A
      critical review of the literature.
AB  - The optimal method for acetabular socket fixation remains controversial. We
      present a critical analysis of the current evidence from a systemic literature
      review of comparative studies, long-term case series, prior literature reviews,
      meta-analysis, and national arthroplasty registry data for cemented and
      uncemented acetabular components to determine the respective survivorship rates,
      overall risk of re-operation, dislocation rates, and wear-related complications.
      Using contemporary techniques, both cemented and uncemented sockets can yield
      good long-term results, but our evaluation suggests that the overall/all cause re
      operation risk is lower for cemented fixation. Until and unless crosslinked
      polyethylene (PE) liners or alternative bearings can prove to yield superior
      outcome in the future, the cemented PE cup remains the gold standard, in all age
      groups, by which every acetabular component should be compared.

PMID- 22134619
TI  - Measurements of intracellular ATP provide new insight into the regulation of
      glycolysis in the yeast Saccharomyces cerevisiae.
AB  - Glycolysis in the yeast Saccharomyces cerevisiae exhibits temporal oscillation
      under anaerobic or semianaerobic conditions. Previous evidence indicated that at
      least two membrane-bound ATPases, the mitochondrial F(0)F(1) ATPase and the
      plasma membrane P-type ATPase (Pma1p), were important in regulating the
      glycolytic oscillation. Measurements of intracellular ATP provide a unique tool
      to understand the role of these membrane ATPases and how their activities are
      regulated. We have constructed a new nanobiosensor that can perform time-resolved
      measurements of intracellular ATP in intact cells. Measurements of the temporal
      behaviour of intracellular ATP in a yeast strain with oscillating glycolysis
      showed that, in addition to oscillation in intracellular ATP, there is an overall
      slow decrease in intracellular ATP because the ATP consumption rate exceeds the
      ATP production in glycolysis. Measurements of the temporal behaviour of
      intracellular ATP in yeast strains lacking either of the two membrane bound
      ATPases have confirmed that F(0)F(1) ATPase and Pma1p contribute significantly to
      the ATP consumption in the cell and to the regulation of glycolytic oscillation.
      Furthermore, our measurements also demonstrate that ATPase activity is under
      strict control. In the absence of glucose ATPase activity is switched off, and
      the intracellular ATP concentration is high. When glucose is added to the cells
      the ATP concentration starts to decrease, because ATP consumption exceeds ATP
      production by glycolysis. Finally, when glucose is used up, the ATP consumption
      stops immediately. Thus, glucose or some compound derived from glucose must be
      involved in controlling the activity of these two ATPases.

PMID- 22134620
TI  - Determinants of time of start of prenatal care and number of prenatal care visits
      during pregnancy among Nepalese women.
AB  - This study is aimed at investigating the factors determining the timing of first
      prenatal care (PNC) visit and the number of PNC visits among a national
      representative sample of Nepali women. Data was drawn from the 2006 Nepal
      Demographic and Health Survey on women age 15-49 years old who had delivery
      within three years prior to the survey (N = 4,136). Multinomial logistic
      regression was used to study the association between socio-demographic variables
      and two outcome variables--the timing of first PNC and number of PNC visits. Most
      of the women (45%) started prenatal care after 3 months of pregnancy while 28%
      had no care. About 43% of women had 1-3 PNC visits, 29% had more than 3 visits.
      Age, education, parity and wealth were associated with both the timing of PNC and
      the number of PNC visits such that older women and those socioeconomically
      disadvantaged had late and fewer PNC visits compared to the younger ones and
      those with socioeconomic advantage, respectively. Women with higher parity and
      those in rural residencies were more likely to delay PNC, have fewer PNC or have
      no care at all. Majority of Nepali women do not attend prenatal care during the
      first trimester of pregnancy contrary to the WHO recommendation for women in
      developing countries. Programmes aimed at improving maternal health in general
      and participation in PNC in particular should target all Nepali women, especially
      those: in rural residencies, with no education, with high parity; older women and
      those from poor households.

PMID- 22134621
TI  - Functional porous organic polymers for heterogeneous catalysis.
AB  - Porous organic polymers (POPs), a class of highly crosslinked amorphous polymers
      possessing nano-pores, have recently emerged as a versatile platform for the
      deployment of catalysts. The bottom-up approach for porous organic polymer
      synthesis provides the opportunity for the design of polymer frameworks with
      various functionalities, for their use as catalysts or ligands. This tutorial
      review focuses on the framework structures and functionalities of catalytic POPs.
      Their structural design, functional framework synthesis and catalytic reactions
      are discussed along with some of the challenges.

PMID- 22134622
TI  - Lack of association between common single nucleotide polymorphisms in the TERT
      CLPTM1L locus and breast cancer in women of African ancestry.
AB  - As one of the most common cancers worldwide, breast cancer places an
      extraordinary burden on the populations of African ancestry. Common SNPs in the
      TERT-CLPTM1L locus have been reported to be associated with several types of
      cancer, including breast cancer. We sought to investigate whether the previously
      reported common single nucleotide polymorphisms (SNPs) in the TERT-CLPTM1L locus
      could also contribute to the breast cancer risk in women of African ancestry. We
      genotyped eleven SNPs in 2,892 women of African descent but were unable to detect
      any significant association between TERT-CLPTM1L SNPs and their predispositions
      for breast cancer risk. Given the differences in linkage disequilibrium patterns
      across populations, our findings suggest that larger independent studies from
      diverse populations are expected to evaluate the importance of the TERT-CLPTM1L
      locus in breast cancer.

PMID- 22134623
TI  - Progression of ductal carcinoma in situ to invasive breast cancer is associated
      with gene expression programs of EMT and myoepithelia.
AB  - Ductal carcinoma in situ (DCIS) is a precursor lesion that can gives rise to
      invasive breast cancer (IBC). It has been proposed that both the nature of the
      lesion and the tumor microenvironment play key roles in progression to IBC. Here,
      laser capture microdissected tissue from pure DCIS and pure IBC were employed to
      define key gene expression profiles in either the epithelial or stromal
      compartment associated with disease progression. Each tissue had distinct gene
      expression profiles, and a DCIS/IBC classifier accurately distinguished DCIS
      versus IBC in multiple independent data sets. However, contrary to other studies
      that profiled DCIS associated with invasive disease, we found that the most
      significant alterations in gene expression were observed in the epithelial
      compartment rather than in the stroma. In particular, genes associated with
      epithelial-to-mesenchymal transition and myoepithelial cell-specific genes were
      enriched in invasive cancer relative to pure DCIS. Such alterations in transcript
      levels were associated with all subtypes of breast cancer, but were particularly
      indicative of poor outcome in ER-negative breast cancer. Together, these studies
      indicate that lesion-specific differences in gene expression associated with
      invasive phenotype are particularly relevant in the progression of DCIS to
      invasive breast cancer.

PMID- 22134624
TI  - Three years of treatment with minodronate in patients with postmenopausal
      osteoporosis.
AB  - The objective of this study was to determine the safety and efficacy of long-term
      minodronate treatment in women with postmenopausal osteoporosis based on re
      analysis of a phase III 2-year clinical trial with a 1-year extension. Women aged
      55-80 years old with fragility fractures were enrolled and randomized to take 1
      mg minodronate or placebo once a day in the original 2-year study. The subjects
      who completed the 2-year study were invited to participate in an additional 1
      year extension in which all subjects were to receive minodronate. Finally, a
      total 380 subjects completed the extension study (186 from the placebo group and
      194 from the minodronate group). Fracture results observed in the extension study
      were consistent with those observed in the first 2 years in minodronate group. In
      contrast, the placebo/minodronate group showed a decreased incidence of new
      vertebral fractures during year 3 compared to that in year 2. In the patients who
      received minodronate in the original 2-year study, lumbar bone mineral density
      (BMD) increased consistently during year 3 and bone turnover markers decreased
      within the first 6 months and remained constant thereafter over 3 years. Similar
      positive effects of minodronate on BMD and bone turnover markers occurred when
      therapy was initiated in the placebo/minodronate group. No new safety concerns
      observed during the extension period compared to the safety observations made
      during the 2-year study. It was concluded that daily administration of 1 mg oral
      minodronate is safe and well tolerated, and that the efficacy of this dose in
      reducing vertebral fracture risk in postmenopausal women over 2 years is
      sustained with continuing treatment.

PMID- 22134625
TI  - Glucocorticoids and relapse and infection rates in anti-neutrophil cytoplasmic
      antibody disease.
AB  - BACKGROUND AND OBJECTIVES: The optimal course of glucocorticoid therapy in anti
      neutrophil cytoplasmic autoantibody (ANCA) disease is unknown. This cohort study
      evaluates effects of glucocorticoid therapy duration on patient outcomes and
      adverse events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study
      assessed 147 patients diagnosed between January 1, 2000 and January 1, 2009 who
      were treated with glucocorticoids and cyclophosphamide. Patients with end stage
      kidney disease at presentation, treatment resistance, or who had died within 6
      months were excluded. Patients were divided into three groups: 0, 5, or >5 mg
      prednisone daily at 6 months after therapy initiation. The latter two groups were
      combined for assessment of adverse events. Wilcoxon rank sum, Kruskal-Wallis, or
      Fisher's exact tests were used for between-group comparisons. Time to relapse was
      evaluated by the Kaplan-Meier method with log-rank test for comparison. RESULTS:
      There were no differences between groups in ANCA specificity, serum creatinine,
      frequency of risk factors for relapse, or length of therapy with
      immunosuppressants. Length of glucocorticoid therapy had no impact on time to
      relapse (hazard ratio, 0.69 [95% confidence interval (CI), 0.23-2.02]; 1.01, [95%
      CI, 0.57-1.81] for the 5-mg and >5-mg groups, respectively), relapse-free
      survival, end stage kidney disease, or death. Patients receiving glucocorticoids
      beyond 6 months had significantly higher incidence of infections (0.64 infections
      per person-year versus 0.39, P<0.0001) and a marginally significant higher
      frequency of new-onset diabetes mellitus (odds ratio, 2.03; 95% CI, 0.94-4.38).
      CONCLUSIONS: Glucocorticoid therapy beyond 6 months is associated with a
      significantly greater risk of infections but not a significantly decreased risk
      of relapse.

PMID- 22134626
TI  - Renal phosphate loss in long-term kidney transplantation.
AB  - BACKGROUND AND OBJECTIVES: Renal phosphate wasting occurs early postkidney
      transplantation as a result of an accumulation of parathyroid hormone and
      fibroblast growth factor 23 from the CKD period. Serum phosphate, parathyroid
      hormone, and fibroblast growth factor 23 return to baseline 1 year postkidney
      transplantation. What happens beyond this period is unknown. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Mineral parameters were obtained from 229 kidney
      transplant recipients at least 1 year posttransplantation; 46 normal subjects and
      202 CKD patients with similar GFR served as controls. Factors associated with
      phosphate metabolism were analyzed. RESULTS: Despite the reduced graft function,
      most kidney transplant recipients had lower serum phosphate than normal subjects
      accompanied by renal phosphate loss. Fibroblast growth factor 23 was mostly lower
      or comparable with normal subjects, whereas parathyroid hormone was elevated in
      most patients. Hyperparathyroidism is also more common among kidney transplant
      recipients compared with CKD patients. Both parathyroid hormone and fibroblast
      growth factor 23 showed relationships with renal phosphate excretion, but only
      parathyroid hormone displayed an independent association. Parathyroid hormone
      showed the highest area under the curve in predicting renal phosphate leak. When
      patients were categorized according to parathyroid hormone and fibroblast growth
      factor 23 levels, only subset of patients with high parathyroid hormone had an
      increased renal phosphate excretion. CONCLUSIONS: Relatively low serum phosphate
      from renal phosphate leak continued to present in long-term kidney
      transplantation. Both parathyroid hormone and fibroblast growth factor 23
      participated in renal tubular phosphate handling, but persistent
      hyperparathyroidism seemed to have a greater influence in this setting.

PMID- 22134627
TI  - A randomized controlled trial comparing mupirocin and polysporin triple ointments
      in peritoneal dialysis patients: the MP3 Study.
AB  - BACKGROUND AND OBJECTIVES: Infectious complications remain a significant cause of
      peritoneal dialysis (PD) technique failure. Topical ointments seem to reduce
      peritonitis; however, concerns over resistance have led to a quest for
      alternative agents. This study examined the effectiveness of applying topical
      Polysporin Triple ointment (P(3)) against mupirocin in a multi-centered, double
      blind, randomized controlled trial. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: PD patients routinely applied either P(3) or mupirocin ointment to
      their exit site. Patients were followed for 18 months or until death or catheter
      removal. The primary study outcome was a composite endpoint of exit-site
      infection (ESI), tunnel infection, or peritonitis. RESULTS: Seventy-five of 201
      randomized patients experienced a primary outcome event (51 peritonitis episodes,
      24 ESIs). No difference was seen in the time to first event for P(3) (13.2
      months; 95% confidence interval, 11.9-14.5) and mupirocin (14.0 months; 95%
      confidence interval, 12.7-15.4) (P=0.41). Twice as many patients reported redness
      at the exit site in the P(3) group (14 versus 6, P=0.10). Over the complete study
      period, a higher rate per year of fungal ESIs was seen in patients using P(3)
      (0.07 versus 0.01; P=0.02) with a corresponding increase in fungal peritonitis
      (0.04 versus 0.00, respectively; P<0.05). CONCLUSIONS: This study shows that P(3)
      is not superior to mupirocin in the prophylaxis of PD-related infections.
      Colonization of the exit site with fungal organisms is of concern and warrants
      further study. As such, the use of P(3) over mupirocin is not advocated in the
      prophylaxis of PD-related infections.

PMID- 22134628
TI  - Selected unusual tumors of the stomach: a review.
AB  - Several unusual stomach tumors have been recently described. In addition, some
      tumors that are often encountered in other sites may rarely occur as primary
      gastric tumors. The diagnostic surgical pathologist needs to be aware of some of
      these lesions to prevent misdiagnosis. This overview discusses the key clinical
      features, pathology, immunohistochemistry, and relevant molecular findings of
      multiple minute gastrointestinal stromal tumors and interstitial cell of Cajal
      hyperplasia, nerve sheath tumors (schwannoma and perineurioma), gastroblastoma,
      granular cell tumor, glomus tumor, plexiform angiomyxoid myofibroblastic tumor,
      and primary clear cell sarcoma of the gastrointestinal tract that occur as
      primary gastric neoplasms.

PMID- 22134629
TI  - Metastatic tumors to the urinary bladder: clinicopathologic study of 11 cases.
AB  - Secondary neoplasms of the urinary bladder are uncommon, with metastatic tumors
      being an even rarer event. The authors studied the clinicopathology of 11 cases
      of metastatic tumors to bladder, which were collected from their archives between
      1995 and 2010. The most common metastases in this series were breast. Some
      unusual metastases, including several not being previously reported, were also
      presented, namely, ileal carcinoid tumor, ileal gastrointestinal stromal tumor,
      ovarian squamous carcinoma, pancreatic gastrinoma, and renal collecting duct
      carcinoma. Vast majority of these patients (10/11, 91%) were female. Ninety
      percent of the patients presented with hematuria and/or obstructive urinary
      symptom as well as bladder lesions in the area of trigone, posterior wall, and/or
      bladder neck. Seven of the 11 patients had a known history of other metastases
      besides the bladder. Most of the patients (4/7, 57%) died within 1 year after
      diagnosis of bladder metastasis. Metastasis must be distinguished from a primary
      bladder neoplasm. Morphology and clinical correlation supplemented with
      immunohistochemical study is critical for the correct diagnosis.

PMID- 22134630
TI  - Uterine glomeruloid hemangioma in a patient without POEMS syndrome.
AB  - Cutaneous glomeruloid hemangioma is a hallmark of POEMS syndrome. These patients
      have elevated serum levels of vascular endothelial growth factor. The authors
      report an extracutaneous uterine glomeruloid hemangioma in an 82-year-old woman
      with a history of breast and endometrial carcinomas. Within the lumen of
      myometrial vessels, a lobular, glomeruloid proliferation of capillary-like CD31
      and vascular endothelial growth factor receptor-1-positive endothelial cells was
      found. The capillary loops were lined by endothelial cells, most of them
      containing PAS-positive and immunoglobulin-positive eosinophilic hyaline globules
      (thanatosomes). This vascular proliferation was consistent with a glomeruloid
      hemangioma. Although an extracutaneous glomeruloid vascular proliferation has
      been found in the retroperitoneal adipose tissue in a patient with POEMS
      syndrome, this study reports what seems to be the first case of visceral
      glomeruloid hemangioma in a patient without POEMS syndrome. The authors
      hypothesize that the glomeruloid endothelial cell proliferation with vascular
      endothelial growth factor receptor-1 expression may be a paraneoplastic
      phenomenon.

PMID- 22134631
TI  - Peripheral dentinogenic ghost cell tumor: report of a case and literature review.
AB  - Peripheral dentinogenic ghost cell tumor is a rare tumor with only 24 cases
      previously described in the English literature. The majority of cases have been
      reported to occur in the anterior part of the jaws. A case occurring in posterior
      (molar region) of the mandible in a 75-year-old edentulous woman is reported. The
      patient presented with a nodular swelling in the left mandible that showed
      erosion (saucerization) of the underlying bone radiographically. On microscopy,
      the tumor showed mainly solid epithelial islands resembling ameloblastoma in
      fibrous connective tissue. The islands were associated with ghost cells and
      dysplastic dentin. This report includes the clinical, radiographic, and
      microscopic features of the patient, in addition to the review of the English
      literature on the tumor.

PMID- 22134632
TI  - Embryonal (undifferentiated) sarcoma of the liver with peripheral angiosarcoma
      differentiation arising in a mesenchymal hamartoma in an adult patient.
AB  - Embryonal (undifferentiated) sarcoma of the liver (ESL) is a rare malignant
      neoplasm composed of undifferentiated sarcomatous tissue. We are presenting a
      case of a 74-year-old woman diagnosed with an ESL arising from a mesenchymal
      hamartoma of the liver (MHL). Both lesions occur typically in childhood, with
      only rare reported cases in adults. Histologically, the mass consisted primarily
      of loose myxoid stroma admixed with bland spindle cells and extensive, cystic
      (lymphangioma-like) degeneration. However, also present peripherally were
      markedly atypical cells (including multi-nucleated forms) and hyaline globules.
      Additionally, atypical cells with a sinusoid tectorial growth pattern were
      identified, which were positive for CD31, CD34 and Factor VIII. The tumor cells
      of ESL are classically described as being negative for tissue-specific
      immunohistochemical markers. However our case demonstrated focal positivity for
      vascular markers CD31, CD34 and Factor VIII and this along with the sinusoidal
      tectorial growth pattern, mimicked an angiosarcoma.

PMID- 22134633
TI  - Chromophobe renal cell carcinoma with heterologous (liposarcomatous)
      differentiation: a case report.
AB  - A 44-year-old woman presented with right flank mass of 6 months duration. A right
      side renal tumor was diagnosed, and a radical nephrectomy was performed.
      Histopathological examination showed chromophobe renal cell carcinoma (CRCC) with
      sarcomatoid transformation. The sarcomatous component contained large pleomorphic
      lipoblasts. The CRCC was positive for Hale's colloidal iron stain, whereas the
      sarcomatous component was negative. Based on histopathological and
      immunohistochemical findings, a diagnosis of sarcomatoid CRCC with heterologous
      liposarcomatous differentiation was made. To the authors' knowledge, this is the
      second reported case of a sarcomatoid CRCC where the sarcomatous component
      displayed features of liposarcoma. The case has been reported for its rarity.

PMID- 22134634
TI  - Rapid access to polycyclic indolines related to the stephacidin alkaloids using a
      radical cascade.
AB  - A new and very rapid access to indoline intermediates useful for the synthesis of
      alkaloids related to the stephacidins has been established using a radical
      cascade process initiated from a sulphur-substituted diketopiperazine.

PMID- 22134635
TI  - Protective effects of thioredoxin-mediated p53 activation in response to mild
      hyperthermia.
AB  - Recently, mild hyperthermia was shown to induce cell cycle arrest at the G2/M
      phase transition without leading to DNA damage. The mechanism of this regulation
      has not yet been elucidated, although p53 has been shown to be activated in
      response to mild hyperthermia. Here, we report the role of thioredoxin (TXN) in
      mild hyperthermia-induced cellular responses. Our data showed that the protein
      levels of p53 and its downstream gene, Gadd45a, which is an indicator of G2/M
      arrest, were significantly decreased in TXN siRNA-treated cells under conditions
      of mild hyperthermia (41C, 60 min) as compared to TXN wild-type cells, implying
      that TXN might play an important role in mild hyperthermia-induced G2/M arrest
      via p53 and Gadd45a activation. Furthermore, the release of cyclin-dependent
      kinase Cdc2, known to be regulated by Gadd45a under G2/M arrest, was inhibited
      from the nucleus for arrest in the G2/M phase in TXN downregulated cells under
      mild hyperthermia. We suggest that G2/M arrest mediated via the TXN-modulated p53
      in response to mild hyperthermia may provide critical insight into the clinical
      use of mild hyperthermia to induce an adaptive response against genotoxic
      stresses.

PMID- 22134636
TI  - Pro-oxidant and antioxidant effects of N-acetylcysteine regulate doxorubicin
      induced NF-kappa B activity in leukemic cells.
AB  - Clinical debate has arisen over the consequences of antioxidant supplementation
      during cancer chemotherapy. While antioxidants may impede the efficacy of
      chemotherapy by scavenging reactive oxygen species and free radicals, it is also
      possible that antioxidants alleviate unwanted chemotherapy-induced toxicity, thus
      allowing for increased chemotherapy doses. These contradictory assertions suggest
      that antioxidant supplementation during chemotherapy treatment can have varied
      outcomes depending on the cellular context. To gain a more robust understanding
      of the role that antioxidants play in chemotherapy, we investigated the dose
      dependent effects of the antioxidant, N-acetylcysteine (NAC), on the redox
      mediated regulation of intracellular signaling. In this study, we systematically
      evaluated the effect of Dox-induced ROS on the NF-kappaB pathway in a pediatric
      acute lymphoblastic leukemia (ALL) cell line by measuring the thiol-based
      oxidative modifications of redox-sensitive proteins within the pathway. We report
      a functional consequence of NAC supplementation during doxorubicin (Dox)
      chemotherapy administration via the NF-kappa B (NF-kappaB) signal transduction
      pathway. The ability of NAC to alter Dox-induced NF-kappaB activity is contingent
      on the ROS-mediated S-glutathionylation of IKK-beta. Moreover, the NAC-dependent
      alteration of intracellular glutathione redox balance, through pro-oxidant and
      antioxidant mechanisms, can be exploited to either promote or inhibit Dox-induced
      NF-kappaB activity in an NAC-concentration-dependent manner. We developed an
      electron-transfer-based computational model that predicts the effect of NAC
      pretreatment on Dox-induced NF-kappaB signaling for a range of NAC and Dox
      treatment combinations.

PMID- 22134637
TI  - Estimating the aquatic emissions and fate of perfluorooctane sulfonate (PFOS)
      into the river Rhine.
AB  - The sources, distribution, levels and sinks of perfluorooctane sulfonate (PFOS)
      estimated to be released from areas of high population density, have been
      explored using the river Rhine as a case study. A comparison between modelled and
      measured data is presented, along with analysis of the importance of PFOS
      sorption in riverine systems. PFOS releases into the Rhine were estimated to be
      325-690 kg/yr based on per capita emission rates of 27-57 MUg day(-1) from a
      population of 33 million living within a 50 km zone either side of the river.
      Sorption of PFOS to suspended particles and sediments may alter its fate in the
      aquatic environment. Therefore available measured and modelled partitioning data
      was assessed, and K(d) values (sorption coefficient) of 7.5 and 20 were selected.
      This resulted in sediment-water ratios of 23-76 : 1, which are similar to ratios
      reported in the literature, and resulted in modelled estimates that <20% of the
      total PFOS entering the Rhine binds to sediments or suspended particles. The
      calculated discharge from the Rhine to the North Sea based on measured data was
      420-2200 kg/yr; our model predictions are in good agreement with these estimates.
      Emission trends were accurately predicted, suggesting population density can be
      effectively used as a surrogate for diffuse PFOS emissions from product use,
      while predicted concentrations were a factor of 2-4 below measured data showing
      the importance of other sources. Transfer of PFOS to sediment is estimated to be
      minimal, and consequently discharges to the North Sea are roughly equal to PFOS
      releases to river water.

PMID- 22134638
TI  - Fungal chitinases: diversity, mechanistic properties and biotechnological
      potential.
AB  - Chitin derivatives, chitosan and substituted chito-oligosaccharides have a wide
      spectrum of applications ranging from medicine to cosmetics and dietary
      supplements. With advancing knowledge about the substrate-binding properties of
      chitinases, enzyme-based production of these biotechnologically relevant sugars
      from biological resources is becoming increasingly interesting. Fungi have high
      numbers of glycoside hydrolase family 18 chitinases with different substrate
      binding site architectures. As presented in this review, the large diversity of
      fungal chitinases is an interesting starting point for protein engineering. In
      this review, recent data about the architecture of the substrate-binding clefts
      of fungal chitinases, in connection with their hydrolytic and transglycolytic
      abilities, and the development of chitinase inhibitors are summarized.
      Furthermore, the biological functions of chitinases, chitin and chitosan
      utilization by fungi, and the effects of these aspects on biotechnological
      applications, including protein overexpression and autolysis during industrial
      processes, are discussed in this review.

PMID- 22134639
TI  - Immunological features and the ability of inhibitory effects on enzymatic
      activity of an epitope vaccine composed of cholera toxin B subunit and B cell
      epitope from Helicobacter pylori urease A subunit.
AB  - Epitope vaccine based on urease of Helicobacter pylori is a promising option for
      prophylactic and therapeutic vaccination against H. pylori infection. In this
      study, we constructed an epitope vaccine with mucosal adjuvant cholera toxin B
      subunit (CTB) and an epitope (UreA(183-203)) of H. pylori urease A subunit named
      CTB-UA. The CTB-UA fusion protein was expressed in Escherichia coli, and the
      purified protein was used for intraperitoneal immunization experiments in BALB/c
      mice. The experimental results indicated that anti-CTB-UA antibody could
      recognize both H. pylori urease A subunit (UreA) and urease B subunit (UreB).
      Besides, the CTB-UA epitope vaccine had good immunogenicity and immunoreactivity
      and could induce specific neutralizing antibodies which showed effectively
      inhibitory effect on the enzymatic activity of H. pylori urease. CTB-UA is a
      promising molecule to be investigated as H. pylori vaccine antigen candidate.

PMID- 22134640
TI  - Characterization of a methane-oxidizing biofilm using microarray, and confocal
      microscopy with image and geostatic analyses.
AB  - A mixed methane-oxidizing biofilm was characterized, concurrently using a number
      of advanced techniques. Community analysis results by microarray exhibited that
      type II members dominated the methanotrophic community, in which Methylocystis
      was most abundant, followed by Methylosinus. Observation results by fluorescent
      in situ hybridization and confocal microscopy showed multiple biofilm colonies
      that were irregular, bell-shaped, with mean thickness of approximately 20 MUm.
      Image analysis results indicated that the relative abundance of methanotrophs
      peaked at a depth of about 5 MUm. Although the biofilm colonies differed in size,
      methanotrophs accounted for 4-9%. Gaussian and linear regression results between
      the biofilm volumes and types I (r (2) = 0.86) and II volumes (r (2) = 0.92),
      respectively, revealed that type I members played a role in the growth of the
      biofilm but only below a threshold volume, whereas type II members supported the
      overall growth. Geostatistical analyses results revealed concentration of types I
      and II methanotrophic individuals with decreasing depth, and randomness between
      the spatial locations and population levels. Collectively, the methane-oxidizing
      biofilm was a highly organized system with methanotrophs and their cohabitants.

PMID- 22134641
TI  - High-level mucosal and systemic immune responses induced by oral administration
      with Lactobacillus-expressed porcine epidemic diarrhea virus (PEDV) S1 region
      combined with Lactobacillus-expressed N protein.
AB  - To develop effective mucosal vaccine formulation against porcine epidemic
      diarrhea virus (PEDV) infection, the DNA fragments encoding spike protein
      immunodominant region S1 and nucleocapsid N of PEDV were inserted into pPG1
      (surface-displayed) or pPG2 (secretory) plasmids followed by
      electrotransformation into Lactobacillus casei (Lc) to yield four recombinant
      strains: PG1-S1, PG2-S1, PG1-N, and PG2-N. After intragastric administration, it
      was observed that live Lc-expressing S1 protein combined with Lc-expressing N
      protein could elicit much more potent mucosal and systemic immune responses than
      the former alone (P < 0.001), however slightly inferior to the latter alone (P >
      0.05). Furthermore, the surface-displayed mixture (PG1-S1+ PG1-N) revealed
      stronger immunogenicity than the secretory mixture (PG2-S1+ PG2-N) as well as
      PEDV-neutralizing potency in vitro (P < 0.001). On 49th day after the last
      immunization, splenocytes were prepared from mice immunized with surface
      displayed mixture, secretory mixture and negative control to be stimulated by
      purified N and S protein, respectively. The results of ELISA analysis showed that
      N protein was capable of inducing a higher level of IL-4 (P < 0.001) and IFN
      gamma (P < 0.001) than S1 protein in the immunized mice. Taken together, Lc
      expressed N protein as molecular adjuvant or immunoenhancer was able to
      effectively facilitate the induction of mucosal and systemic immune responses by
      Lc-expressing S1 region.

PMID- 22134642
TI  - Comparative metagenomic, phylogenetic and physiological analyses of soil
      microbial communities across nitrogen gradients.
AB  - Terrestrial ecosystems are receiving elevated inputs of nitrogen (N) from
      anthropogenic sources and understanding how these increases in N availability
      affect soil microbial communities is critical for predicting the associated
      effects on belowground ecosystems. We used a suite of approaches to analyze the
      structure and functional characteristics of soil microbial communities from
      replicated plots in two long-term N fertilization experiments located in
      contrasting systems. Pyrosequencing-based analyses of 16S rRNA genes revealed no
      significant effects of N fertilization on bacterial diversity, but significant
      effects on community composition at both sites; copiotrophic taxa (including
      members of the Proteobacteria and Bacteroidetes phyla) typically increased in
      relative abundance in the high N plots, with oligotrophic taxa (mainly
      Acidobacteria) exhibiting the opposite pattern. Consistent with the phylogenetic
      shifts under N fertilization, shotgun metagenomic sequencing revealed increases
      in the relative abundances of genes associated with DNA/RNA replication, electron
      transport and protein metabolism, increases that could be resolved even with the
      shallow shotgun metagenomic sequencing conducted here (average of 75 000 reads
      per sample). We also observed shifts in the catabolic capabilities of the
      communities across the N gradients that were significantly correlated with the
      phylogenetic and metagenomic responses, indicating possible linkages between the
      structure and functioning of soil microbial communities. Overall, our results
      suggest that N fertilization may, directly or indirectly, induce a shift in the
      predominant microbial life-history strategies, favoring a more active,
      copiotrophic microbial community, a pattern that parallels the often observed
      replacement of K-selected with r-selected plant species with elevated N.

PMID- 22134643
TI  - Microbial diversity of biofilm communities in microniches associated with the
      didemnid ascidian Lissoclinum patella.
AB  - We assessed the microbial diversity and microenvironmental niche characteristics
      in the didemnid ascidian Lissoclinum patella using 16S rRNA gene sequencing,
      microsensor and imaging techniques. L. patella harbors three distinct microbial
      communities spatially separated by few millimeters of tunic tissue: (i) a biofilm
      on its upper surface exposed to high irradiance and O(2) levels, (ii) a cloacal
      cavity dominated by the prochlorophyte Prochloron spp. characterized by strong
      depletion of visible light and a dynamic chemical microenvironment ranging from
      hyperoxia in light to anoxia in darkness and (iii) a biofilm covering the
      underside of the animal, where light is depleted of visible wavelengths and
      enriched in near-infrared radiation (NIR). Variable chlorophyll fluorescence
      imaging demonstrated photosynthetic activity, and hyperspectral imaging revealed
      a diversity of photopigments in all microhabitats. Amplicon sequencing revealed
      the dominance of cyanobacteria in all three layers. Sequences representing the
      chlorophyll d containing cyanobacterium Acaryochloris marina and anoxygenic
      phototrophs were abundant on the underside of the ascidian in shallow waters but
      declined in deeper waters. This depth dependency was supported by a negative
      correlation between A. marina abundance and collection depth, explained by the
      increased attenuation of NIR as a function of water depth. The combination of
      microenvironmental analysis and fine-scale sampling techniques used in this
      investigation gives valuable first insights into the distribution, abundance and
      diversity of bacterial communities associated with tropical ascidians. In
      particular, we show that microenvironments and microbial diversity can vary
      significantly over scales of a few millimeters in such habitats; which is
      information easily lost by bulk sampling.

PMID- 22134644
TI  - Ammonia-oxidizing archaea have more important role than ammonia-oxidizing
      bacteria in ammonia oxidation of strongly acidic soils.
AB  - Increasing evidence demonstrated the involvement of ammonia-oxidizing archaea
      (AOA) in the global nitrogen cycle, but the relative contributions of AOA and
      ammonia-oxidizing bacteria (AOB) to ammonia oxidation are still in debate.
      Previous studies suggest that AOA would be more adapted to ammonia-limited
      oligotrophic conditions, which seems to be favored by protonation of ammonia,
      turning into ammonium in low-pH environments. Here, we investigated the
      autotrophic nitrification activity of AOA and AOB in five strongly acidic soils
      (pH<4.50) during microcosm incubation for 30 days. Significantly positive
      correlations between nitrate concentration and amoA gene abundance of AOA, but
      not of AOB, were observed during the active nitrification. (13)CO(2)-DNA-stable
      isotope probing results showed significant assimilation of (13)C-labeled carbon
      source into the amoA gene of AOA, but not of AOB, in one of the selected soil
      samples. High levels of thaumarchaeal amoA gene abundance were observed during
      the active nitrification, coupled with increasing intensity of two denaturing
      gradient gel electrophoresis bands for specific thaumarchaeal community. Addition
      of the nitrification inhibitor dicyandiamide (DCD) completely inhibited the
      nitrification activity and CO(2) fixation by AOA, accompanied by decreasing
      thaumarchaeal amoA gene abundance. Bacterial amoA gene abundance decreased in all
      microcosms irrespective of DCD addition, and mostly showed no correlation with
      nitrate concentrations. Phylogenetic analysis of thaumarchaeal amoA gene and 16S
      rRNA gene revealed active (13)CO(2)-labeled AOA belonged to groups 1.1a
      associated and 1.1b. Taken together, these results provided strong evidence that
      AOA have a more important role than AOB in autotrophic ammonia oxidation in
      strongly acidic soils.

PMID- 22134645
TI  - Geographically structured host specificity is caused by the range expansions and
      host shifts of a symbiotic fungus.
AB  - The inability to associate with local species may constrain the spread of
      mutualists arriving to new habitats, but the fates of introduced, microbial
      mutualists are largely unknown. The deadly poisonous ectomycorrhizal fungus
      Amanita phalloides (the death cap) is native to Europe and introduced to the East
      and West Coasts of North America. By cataloging host associations across the two
      continents, we record dramatic changes in specificity among the three ranges. On
      the East Coast, where the fungus is restricted in its distribution, it associates
      almost exclusively with pines, which are rarely hosts of A. phalloides in its
      native range. In California, where the fungus is widespread and locally abundant,
      it associates almost exclusively with oaks, mirroring the host associations
      observed in Europe. The most common host of the death cap in California is the
      endemic coast live oak (Quercus agrifolia), and the current distribution of A.
      phalloides appears constrained within the distribution of Q. agrifolia. In
      California, host shifts to native plants are also associated with a near doubling
      in the resources allocated to sexual reproduction and a prolonged fruiting
      period; mushrooms are twice as large as they are elsewhere and mushrooms are
      found throughout the year. Host and niche shifts are likely to shape the
      continuing range expansion of A. phalloides and other ectomycorrhizal fungi
      introduced across the world.

PMID- 22134646
TI  - An improved Greengenes taxonomy with explicit ranks for ecological and
      evolutionary analyses of bacteria and archaea.
AB  - Reference phylogenies are crucial for providing a taxonomic framework for
      interpretation of marker gene and metagenomic surveys, which continue to reveal
      novel species at a remarkable rate. Greengenes is a dedicated full-length 16S
      rRNA gene database that provides users with a curated taxonomy based on de novo
      tree inference. We developed a 'taxonomy to tree' approach for transferring group
      names from an existing taxonomy to a tree topology, and used it to apply the
      Greengenes, National Center for Biotechnology Information (NCBI) and cyanoDB
      (Cyanobacteria only) taxonomies to a de novo tree comprising 408,315 sequences.
      We also incorporated explicit rank information provided by the NCBI taxonomy to
      group names (by prefixing rank designations) for better user orientation and
      classification consistency. The resulting merged taxonomy improved the
      classification of 75% of the sequences by one or more ranks relative to the
      original NCBI taxonomy with the most pronounced improvements occurring in under
      classified environmental sequences. We also assessed candidate phyla (divisions)
      currently defined by NCBI and present recommendations for consolidation of 34
      redundantly named groups. All intermediate results from the pipeline, which
      includes tree inference, jackknifing and transfer of a donor taxonomy to a
      recipient tree (tax2tree) are available for download. The improved Greengenes
      taxonomy should provide important infrastructure for a wide range of
      megasequencing projects studying ecosystems on scales ranging from our own bodies
      (the Human Microbiome Project) to the entire planet (the Earth Microbiome
      Project). The implementation of the software can be obtained from
      http://sourceforge.net/projects/tax2tree/.

PMID- 22134647
TI  - Bacterial cis-2-unsaturated fatty acids found in the cystic fibrosis airway
      modulate virulence and persistence of Pseudomonas aeruginosa.
AB  - There is an increasing appreciation of the polymicrobial nature of many bacterial
      infections such as those associated with cystic fibrosis (CF) and of the
      potentially important role for interspecies interactions in influencing both
      bacterial virulence and response to therapy. Patients with CF are often co
      infected with Pseudomonas aeruginosa and other pathogens including Burkholderia
      cenocepacia and Stenotrophomonas maltophilia. These latter bacteria produce
      signal molecules of the diffusible signal factor (DSF) family, which are cis-2
      unsaturated fatty acids. We have previously shown by in vitro studies that DSF
      from S. maltophilia leads to altered biofilm formation and increased resistance
      to antibiotics by P. aeruginosa; these responses of P. aeruginosa require the
      sensor kinase PA1396. Here we show that DSF signals are present in sputum taken
      from patients with CF. Presence of these DSF signals was correlated with patient
      colonization by S. maltophilia and/or B. cenocepacia. Analysis of 50 clinical
      isolates of P. aeruginosa showed that each responded to the presence of synthetic
      DSF by increased antibiotic resistance and these strains demonstrated little
      sequence variation in the PA1396 gene. In animal experiments using CF
      transmembrane conductance regulator knockout mice, the presence of DSF promoted
      P. aeruginosa persistence. Furthermore, antibiotic resistance of P. aeruginosa
      biofilms grown on human airway epithelial cells was enhanced in the presence of
      DSF. Taken together, these data provide substantial evidence that interspecies
      DSF-mediated bacterial interactions occur in the CF lung and may influence the
      efficacy of antibiotic treatment, particularly for chronic infections involving
      persistence of bacteria.

PMID- 22134648
TI  - Denitrification likely catalyzed by endobionts in an allogromiid foraminifer.
AB  - Nitrogen can be a limiting macronutrient for carbon uptake by the marine
      biosphere. The process of denitrification (conversion of nitrate to gaseous
      compounds, including N(2) (nitrogen gas)) removes bioavailable nitrogen,
      particularly in marine sediments, making it a key factor in the marine nitrogen
      budget. Benthic foraminifera reportedly perform complete denitrification, a
      process previously considered nearly exclusively performed by bacteria and
      archaea. If the ability to denitrify is widespread among these diverse and
      abundant protists, a paradigm shift is required for biogeochemistry and marine
      microbial ecology. However, to date, the mechanisms of foraminiferal
      denitrification are unclear, and it is possible that the ability to perform
      complete denitrification is because of the symbiont metabolism in some
      foraminiferal species. Using sequence analysis and GeneFISH, we show that for a
      symbiont-bearing foraminifer, the potential for denitrification resides in the
      endobionts. Results also identify the endobionts as denitrifying pseudomonads and
      show that the allogromiid accumulates nitrate intracellularly, presumably for use
      in denitrification. Endobionts have been observed within many foraminiferal
      species, and in the case of associations with denitrifying bacteria, may provide
      fitness for survival in anoxic conditions. These associations may have been a
      driving force for early foraminiferal diversification, which is thought to have
      occurred in the Neoproterozoic era when anoxia was widespread.

PMID- 22134650
TI  - The French functional physical therapy method for the treatment of congenital
      clubfoot.
AB  - The French method, also called the functional physical therapy method, is a
      combination of physiotherapy, splinting and surgery a la carte. The French
      functional physical therapy method consists of daily manipulations of the
      newborn's clubfoot by a specialized physical therapist, stimulation of the
      muscles around the foot and temporary immobilization of the foot with elastic and
      nonelastic adhesive taping. Physiotherapy is optimized by early triceps surae
      lengthening. Sequences of plaster can also be used. If conservative treatment is
      no longer effective, surgery should be considered. Mini-invasive surgery is a
      complementary procedure to nonoperative treatment (surgery 'a la carte'). The
      French method reduces but does not eliminate the need for mini-invasive surgical
      procedures. Equinus is the most difficult deformity to treat; posterior release
      is sometimes necessary in a severe foot. Very severe feet (stiff-stiff; score, 16
      20) are still a challenge. However, regular manipulations and splinting improve
      foot morphology and stiffness, and, ultimately, make surgery easier and less
      extensive. From the French method to the Ponseti method, the Hybrid method or the
      'the third way', combining the advantages of both methods, is the future. The
      primary reason for relapses is the inability of families to maintain the
      correction initially achieved. The aim of this work is to provide an overview of
      the French functional physical therapy method and to help understand how it has
      evolved over time.

PMID- 22134649
TI  - Contrasting denitrifier communities relate to contrasting N2O emission patterns
      from acidic peat soils in arctic tundra.
AB  - Cryoturbated peat circles (that is, bare surface soil mixed by frost action; pH 3
      4) in the Russian discontinuous permafrost tundra are nitrate-rich 'hotspots' of
      nitrous oxide (N(2)O) emissions in arctic ecosystems, whereas adjacent unturbated
      peat areas are not. N(2)O was produced and subsequently consumed at pH 4 in
      unsupplemented anoxic microcosms with cryoturbated but not in those with
      unturbated peat soil. Nitrate, nitrite and acetylene stimulated net N(2)O
      production of both soils in anoxic microcosms, indicating denitrification as the
      source of N(2)O. Up to 500 and 10 MUM nitrate stimulated denitrification in
      cryoturbated and unturbated peat soils, respectively. Apparent maximal reaction
      velocities of nitrite-dependent denitrification were 28 and 18 nmol N(2)O g(DW)(
      1) h(-1), for cryoturbated and unturbated peat soils, respectively. Barcoded
      amplicon pyrosequencing of narG, nirK/nirS and nosZ (encoding nitrate, nitrite
      and N(2)O reductases, respectively) yielded ~49 000 quality-filtered sequences
      with an average sequence length of 444 bp. Up to 19 species-level operational
      taxonomic units were detected per soil and gene, many of which were distantly
      related to cultured denitrifiers or environmental sequences. Denitrification
      associated gene diversity in cryoturbated and in unturbated peat soils differed.
      Quantitative PCR (inhibition-corrected per DNA extract) revealed higher copy
      numbers of narG in cryoturbated than in unturbated peat soil. Copy numbers of
      nirS were up to 1000 * higher than those of nirK in both soils, and nirS nirK(-1)
      copy number ratios in cryoturbated and unturbated peat soils differed. The
      collective data indicate that the contrasting N(2)O emission patterns of
      cryoturbated and unturbated peat soils are associated with contrasting
      denitrifier communities.

PMID- 22134651
TI  - Persistent clubfoot deformity following treatment by the Ponseti method.
AB  - The Ponseti method of clubfoot correction is now widely practiced worldwide.
      Initial correction rates are nearly 100%, but subsequent relapses may occur in up
      to one-third of patients. Very little has been written by anyone other than Dr
      Ponseti about the characterization and treatment of recurrent clubfoot deformity
      following use of the Ponseti method. This review paper is the first one which
      draws together the current literature on the topic.

PMID- 22134652
TI  - External fixation in clubfoot treatment - a review of the literature.
AB  - The treatment of neglected or relapsed clubfoot is still a challenge. Extensive
      open surgeries may lead to postoperative scarring and various
      complications.Gradual distraction using circular fixators for treatment of these
      cases was described by many researchers in the last decades. Different techniques
      were used with and without open surgeries. Recently the Taylor Spatial Frame was
      described for clubfoot correction using the principles of the Ponseti technique.
      Results of treatment using different techniques are described in this review.
      External fixation with soft tissue distraction even without open surgery is an
      effective treatment for neglected or relapsed clubfoot.

PMID- 22134653
TI  - Special issue on clubfoot preface: Bridging the world - a tribute to professor
      Henri Bensahel.

PMID- 22134654
TI  - Enhanced expression of rabies virus surface G-protein in Escherichia coli using
      SUMO fusion.
AB  - Fusion systems are known to increase the expression of difficult to express
      recombinant proteins in soluble form to facilitate their purification. Rabies
      glycoprotein was also tough to express at sufficient level in soluble form in
      both E. coli and plant. The present work was aimed to over-express and purify
      this membrane protein from soluble extract of E. coli. Fusion of Small Ubiqutin
      like Modifier (SUMO) with rabies glycoprotein increased ~1.5 fold higher
      expression and ~3.0 fold solubility in comparison to non-fused in E. coli. The
      SUMO fusion also simplified the purification process. Previously engineered
      rabies glycoprotein gene in tobacco plants provides complete protection to mice,
      but the expression was very low for purification. Our finding demonstrated that
      the SUMO-fusion was useful for enhancing expression and solubility of the
      membrane protein and again proves to be a good alternative technology for
      applications in biomedical and pharmaceutical research.

PMID- 22134655
TI  - Eicosanoid signalling pathways in the development and progression of colorectal
      cancer: novel approaches for prevention/intervention.
AB  - Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and
      cytochrome P-450 epoxygenase (EPOX) pathways leads to the generation of
      biologically active eicosanoids, including prostanoids, leukotrienes,
      hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and
      hydroperoxyeicosatetraenoic acids. Eicosanoid expression levels vary during tumor
      development and progression of a range of malignancies, including colorectal
      cancer. The actions of these autocoids are also directly influenced by diet, as
      demonstrated by recent evidence for omega-3 fatty acids in colorectal cancer
      (CRC) prevention and/or treatment. Eicosanoids regulate CRC development and
      progression, while inhibition of these pathways has generally been shown to
      inhibit tumor growth/progression. A progressive sequence of colorectal cancer
      development has been identified, ranging from normal colon, to colitis,
      dysplasia, and carcinoma. While both COX and LOX inhibition are both promising
      candidates for colorectal cancer prevention and/or treatment, there is an urgent
      need to understand the mechanisms through which these signalling pathways mediate
      their effects on tumorigenesis. This will allow identification of safer, more
      effective strategies for colorectal cancer prevention and/or treatment. In
      particular, binding to/signalling through prostanoid receptors have recently been
      the subject of considerable interest in this area. In this review, we discuss the
      role of the eicosanoid signalling pathways in the development and progression of
      colorectal cancer. We discuss the effects of the eicosanoids on tumor cell
      proliferation, their roles in cell death induction, effects on angiogenesis,
      migration, invasion and their regulation of the immune response. Signal
      transduction pathways involved in these processes are also discussed. Finally,
      novel approaches targeting these arachidonic acid-derived eicosanoids (using
      pharmacological or natural agents) for chemoprevention and/or treatment of
      colorectal cancer are outlined.

PMID- 22134656
TI  - Role of parathymic lymph nodes in metastatic tumor development.
AB  - Parathymic lymph nodes as potential sites of tumor progression have been
      neglected in humans. We have established a rat renal capsule-parathymic lymph
      node model to study in vivo metastasis. Epithelial liver carcinoma (HeDe) and
      mesenchymal mesoblastic nephroma (NeDe) cell lines have been established after
      inducing chemical carcinogenesis in newborn Fisher 344 inbred rats by N
      nitrosodimethylamine. Implanting the exact number of tumor cells (HeDe, NeDe)
      under the renal capsule allowed the standardization and timing of metastatic
      development. Tumor cells released from the primary tumor in the peritoneal cavity
      were drained to the parathymic lymph nodes (PTNs) as sentinel lymph nodes.
      Similarly, tumor cells injected i.p. were engulfed by macrophages, drained
      through the transdiaphragmatic channels, and transported to the thoracal
      lymphatics, primarily to PTNs. Tumor cells after transdiaphragmic drainage can
      enter both anterior mammary and parathymic sentinel lymph nodes. The potential
      common origin can shed new light on the metastatic cell progression of PTNs and
      mammary tumors.

PMID- 22134657
TI  - [Odontogenic tumours in the dog and cat].
AB  - OBJECTIVE: Odontogenic tumours in the dog and cat, as well as in other domestic
      animals and in man occur rarely and can be difficult to diagnose. In the present
      study a great number of canine and feline odontogenic tumours were investigated
      histopathologically and classified to provide an appropriate basis for the
      evaluation of these tumours. MATERIAL AND METHODS: In a retrospective study of a
      total of 1390 canine and 317 feline oral tumours from the years 1977 to 2007, the
      tumours of odontogenic origin were selected, characterized histopathologically
      and classified according to the current human WHO-classification of odontogenic
      tumours (2005) and the current veterinary WHO-classification of odontogenic
      tumours (2003). RESULTS: 18% (n=250) of the canine and 3.2% (n=10) of the feline
      oral tumours proved to be of odontogenic origin. They could be divided into
      benign (epithelial, epithelial and ectomesenchymal, ectomesenchymal) and
      malignant (carcinomas and sarcomas) odontogenic tumours with a total of 12
      different entities. The odontogenic fibroma was the most common canine (n=167)
      and feline (n=4) odontogenic tumour. The second most common odontogenic tumour
      for canines was ameloblastoma (n=74) and that for felines was ameloblastic
      fibroma (n=2). Four of the 12 entities could be classified according to both WHO
      classifications of odontogenic tumours. Seven and two of the 12 entities could
      only be classified according to the current human WHO-classification and
      veterinary WHO-classification, respectively. CONCLUSION AND CLINICAL RELEVANCE:
      The prognostic evaluation of tumours is of the greatest clinical relevance and
      calls for an absolutely certain diagnosis. Particularly in the case of the rare
      and histomorphologically complex odontogenic tumours the current veterinary WHO
      classification does not meet this requirement and needs to be revised and
      extended. The human WHO-classification proved to be more efficient when compared
      to the veterinary one.

PMID- 22134658
TI  - Observer variability and sensitivity of radiographic diagnosis of canine medial
      coronoid disease.
AB  - OBJECTIVE: Medial coronoid disease (MCD) is a very common form of elbow joint
      disease and it's radiographic diagnosis can be challenging since it is frequently
      based on the detection of rather subtle primary or secondary changes than on a
      large primary lesion. We hypothesized that accuracy of radiographic diagnosis of
      MCD is highly dependent on training and experience level. METHODS: Radiographs of
      102 canine elbows were evaluated for MCD by four observers with different levels
      of training and experience. All elbows underwent CT scans and arthroscopy.
      Sensitivity and specificity of radiographic and CT interpretation was determined
      using arthroscopy as a gold standard. Interobserver and intraobserver agreement
      (reliability and repeatability) were assessed by using Cohen's Kappa (kappa)
      statistic. RESULTS: The sensitivity (92.4-96.7%) of the two experienced observers
      was almost comparable to that of CT (100%) and significantly higher than that of
      the two less experienced observers (77.2-80.4%). Reliability of the radiographic
      diagnosis of MCD was better between observers with higher experience level
      (kappa= 0.74) than between observers of lower or different experience levels
      (kappa=0.07-0.42). Repeatability was better in experienced (kappa= 0.73-0.88)
      than in less experienced observers (kappa= 0.31-0.42). CONCLUSION: Our results
      confirm that training and experience play important roles in reaching high
      sensitivity, reliability and repeatability for the radiographic diagnosis of MCD.
      CLINICAL RELEVANCE: Although radiography is inferior to CT in imaging of the
      medial coronoid process itself, sensitivity of radiographic diagnosis MCD can be
      significantly improved with observer experience almost reaching that of CT.
      Therefore, it is advised that radiographic screening for MCD should be performed
      by specialists experienced in the radiographic evaluation of elbow joint disease.

PMID- 22134659
TI  - [Lameness and osteoarthritis development following Tibial Plateau Leveling
      Osteotomy (TPLO) and potential prognostic predictors. A long-term retrospective
      study].
AB  - OBJECTIVE: Evaluation of lameness and osteoarthritis (OA) progression following
      Tibial Plateau Leveling Osteotomy (TPLO) in dogs with naturally-occurring rupture
      of the cranial cruciate ligament (CCL) and investigation of factors with
      potential influence on long-term outcome. MATERIAL AND METHODS: In a
      retrospective clinical study medical records of 119 client-owned dogs (135
      operated stifle joints) and corresponding client-questionnaires were reviewed,
      collecting data on radiologic and surgery results, course of surgery and
      complications. In a check-up, orthopaedic examination and stifle radiographs were
      performed to assess status quo of OA, lameness, and progression of OA. RESULTS:
      58 dogs (66 stifle joints) could be examined clinically and radiologically,
      whereas 61 dogs (69 stifle joints) were re-checked by client-questionnaire only.
      Up to 6.8 years after TPLO surgery, in 90.4% of all cases lameness results were
      judged "excellent" (n=84) or "good" (n=38). In the long term, there was a
      moderate but significant progression of OA following TPLO surgery. Patients with
      totally ruptured CCL were significantly more likely to have meniscal injury than
      dogs with partially ruptured CCL. Dogs with partial meniscectomy had a
      significantly higher rate of "excellent" long-term clinical results and less
      frequently showed progression of OA compared to those having the meniscus
      released or left untouched. The overall complication rate was 22.2% (n=30), with
      the type of complication having no influence on the long-term clinical outcome.
      CONCLUSIONS AND CLINICAL RELEVANCE: Regarding lameness, the long-term outcome
      following TPLO is very satisfying. Early surgical treatment of CCL rupture using
      TPLO can help to decrease the likelihood of OA progression. Partial medial
      meniscectomy may help to avoid repeated surgery due to subsequent meniscal injury
      without having a negative impact on long-term functional outcome or the
      progression of OA in the affected joint. Neither long-term clinical results,
      especially regarding lameness, nor OA were impaired by previous surgery prior to
      TPLO or the occurrence of complications associated with TPLO surgery.

PMID- 22134660
TI  - [Squeezing of the spermatic cord using a Pean clamp is not suitable for
      elimination of testicular function in the rabbit].
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of three different
      methods for squeezing of the spermatic cord as bloodless castration in rabbits
      according to the "Burdizzo"-method used for ruminants. MATERIALS AND METHODS: In
      18 anaesthetized male rabbits (group 1-3) spermatic cords were squeezed twice
      using three different methods according to Burdizzo: using a Pean haemostat for 3
      minutes (group 1, n=10) or 10 minutes (group 2, n=4) or by use of a Doyen
      intestine clamp for 3 minutes (group 3, n=4). Seven males serving as controls
      underwent surgical castration under general anaesthesia. Animals were daily
      examined until day 7, and on days 14 and 90. Blood samples for testosterone
      measurement were taken on days 1 and 90. On day 90, all animals of groups 1-3
      were surgically neutered and testis examined histologically in comparison with
      group 4. RESULTS: A swelling of the squeezing site was obvious in all animals of
      group 1-3 which was - like pain reaction - most obvious in group 1. Temporary
      changes in testicular consistency, as well as inflammation signs were observed in
      testes, epididymides and spermatic cords. During the course of the study, testes
      size increased (p<0.0001) independently of the group. Testosterone was within the
      physiological range in group 1-3 and differed significantly from group 4
      (p=0.0002). Histology revealed normal spermatogenesis and fully elongated sperm
      in testes and epididymides. CONCLUSION: None of the three bloodless methods used
      led to testicular shrinking, basal testosterone concentration and disturbed
      spermatogenesis which would be a suitable marker for testicular atrophy
      indicating castration. CLINICAL RELEVANCE: Although bloodless castration seems to
      be an interesting alternative to surgery in rabbits, none of the methods used was
      successful in inducing castration effects.

PMID- 22134661
TI  - [Fractures and luxations in small mammals].
AB  - Most traumata in small mammals occur at home. Diagnosis and therapy can be
      compared with that in the dog and cat, but species-specific differences have to
      be considered. For fracture treatment a butterfly-cast can be sufficient for
      stabilization in special cases. In most cases satisfying results can be obtained
      with a "tie-in-fixator" treatment. Dislocations of the elbow joint are treated by
      reduction or stabilization through suture techniques or temporary arthrodesis.

PMID- 22134662
TI  - [Review of 40 years AO/ASIF. The development of the Veterinary Surgical Working
      Group for Osteosynthesis Questions(AO) in Veterinary Medicine (AOVET) and a
      systematic operative fracture treatment in animals].
AB  - With respect to the founding of the AOVET in 1969, the development of the
      systematic osteosynthesis in large and small animals is reviewed. With the
      introduction of the stable OS techniques corresponding to the principles and
      operative techniques developed by the organization of ASIF/AO (hum), the
      systematic operative fracture treatment in animals expanded remarkably. The
      application of the "absolutely" stable compression osteosynthesis was the basis
      for the successful fracture treatment in large animals. The systematic
      osteosynthesis in small animals was realized through the generation of a
      multitude of stabilization techniques for the different fracture types in the
      various anatomical areas and for special orthopaedic interventions. This was
      achieved through a specifically developed implant- instrument system and
      corresponding operation methods. This development was supported by instruction
      courses, published manuals and visiting fellowships. The extensive collaboration
      in research and development led to an increasing understanding of the diverse
      bone healing processes. The AOVET enjoyed a progressing integration into the
      AO/ASIF (hum) organization.

PMID- 22134663
TI  - Extra-articular stabilization of the cranial cruciate deficient stifle with
      anchor systems.
AB  - Complete or partial rupture of the cranial cruciate ligament (CCL) is a common
      injury of the canine stifle. Most practicing veterinarians would agree that
      optimal outcome is best achieved with surgical intervention. A popular method of
      stabilization is an extra-articular suture stabilization. The objective of this
      manuscript is to describe suture placement in a more isometric position as
      compared to traditional suture placement. A second objective is to introduce the
      veterinary surgeon to novel anchor products used for stabilization.

PMID- 22134664
TI  - [Treatment of acute pancreatitis in the dog].

PMID- 22134665
TI  - Single cell analysis at the nanoscale.
AB  - The fundamental life processes such as signal transduction, intracellular
      trafficking, protein degradation, and DNA repair often occur in nanometric
      subcellular compartments. It is essential to conduct single cell analysis
      specifically at the nanoscale to fully understand the critical cellular processes
      while providing important medical applications. However, there are great
      challenges in achieving high spatial resolution in single cells for uncovering
      spatial heterogeneity, high sensitivity for biomolecule detections and high
      specificity in complicated cellular environment. In this tutorial review, we
      survey recent progress toward single cell analysis at the nanoscale by
      emphasizing how the advancement in nanotechnology has brought a plethora of
      nanotools to interrogate single cells with high spatiotemporal resolutions. In
      particular, analysis principle, nanoscale probe fabrication, high resolution
      cellular analysis, data collection and processing are introduced. New cell
      biochemistry and biology insights revealed by the unique single cell analysis
      methods are highlighted. The perspectives on future opportunities and unsolved
      challenges are also discussed.

PMID- 22134666
TI  - The evaluation of the effects of hyperbaric oxygen therapy on new bone formation
      obtained by distraction osteogenesis in terms of consolidation periods.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of hyperbaric oxygen
      therapy on new bone formation obtained by distraction osteogenesis in long- or
      short-term consolidation periods. MATERIALS AND METHODS: Twenty-four rabbits were
      used. The animals were divided into two groups of 12 animals each, and vertical
      mandibular distraction osteogenesis was performed. Hyperbaric oxygen therapy was
      administered in the first group. Each group was subdivided into two subgroups
      according to the 30- and 60-day consolidation period. The acquired bone amounts
      were compared according to their radiographic density and histopathology.
      RESULTS: Histopathologically, in the experimental group, callus formation was
      increased and the new bone was more mineralized. According to the radiographic
      densitometry analyses, there were no statistically significant differences
      between the 30-day consolidated subgroups of the experimental group and the 60
      day consolidated subgroup of the control group (p = 0.873). CONCLUSION:
      Hyperbaric oxygen therapy can be used to increase the quality and the quantity of
      bone and to decrease the maturation time which may shorten the consolidation
      period of vertical distraction osteogenesis. CLINICAL RELEVANCE: The effect of
      hyperbaric oxygen therapy on vertical distraction osteogenesis procedure
      according to consolidation periods has been determined. Hyperbaric oxygen therapy
      may increase the quality and the quantity of bone and shorten the consolidation
      period.

PMID- 22134667
TI  - Depth of cure and mechanical properties of nano-hybrid resin-based composites
      with novel and conventional matrix formulation.
AB  - OBJECTIVES: This study's purpose was to evaluate the depth of cure (DOC) and the
      variation of mechanical properties with depth of two nano-hybrid resin-based
      composites (RBCs) containing a novel monomer composition based on dimer-acid
      derivatives (h-Da) or rather tricyclodecane-urethane structure (TCD-urethane)
      compared to three conventionally formulated nano-hybrid RBCs based on hardness
      profile measurements. MATERIALS AND METHODS: Specimens were produced through
      different layering techniques (bulk, incremental) and curing times (10, 20, and
      40 s). Mechanical properties (Vickers hardness (HV), modulus of elasticity (E))
      were evaluated every 100 MUm longitudinally throughout the bisected samples using
      an automatic micro-hardness indenter. DOC was determined as the depth at which
      the 80% hardness cutoff value in relation to the surface hardness was reached.
      Results were compared using one- and multiple-way ANOVA, Tukey HSD post-hoc test
      (alpha = 0.05) and partial eta-squared statistic. RESULTS: Increasing curing time
      resulted in a significant increase in DOC. Generally, the novel-formulated
      materials showed higher DOC values. "Curing time" and "material" showed the
      strongest effect on DOC. Starting in 4 mm depth, significantly higher HV and E
      was reached for incremental compared to bulk-curing technique. Values in 0.1 and
      2 mm depth (bulk, incremental) as well as in 4 mm depth (incremental) were
      independent from curing time, while in greater depths, values generally increased
      with curing time. "Filling technique" and "material" performed the strongest
      influence on mechanical properties. CONCLUSIONS: Within the limits of this study,
      the novel-formulated RBCs showed better performance concerning DOC compared to
      conventional materials. CLINICAL RELEVANCE: For cavities deeper than 3 mm, all
      tested materials should be placed incrementally to ensure adequate
      polymerization. In large cavities (>=6 mm), the lowest increment should be cured
      at least 40 s. The novel-formulated RBCs might be cured in comparatively bigger
      increments.

PMID- 22134668
TI  - Metastatic neuroblastoma of the mandible: a cytogenetic and molecular genetic
      study.
AB  - Neuroblastoma (NB) jaw metastases are rare. Here, we report on cytogenetic and
      genetic studies on metastatic NB to the mandible. A 7-year-old boy, with an
      abdominal neuroblastoma, presented with a mass of the left body of the mandible.
      Cytogenetic analysis of the original tumor and the mandibular lesion biopsies
      revealed similar heterogenous subclones with 42 ~ 47,XY,+der(1)(q11 -> qter),
      2,del(7)(q21.1 -> qter),-8,-9,-10,-11,del(11)(q13.3 -> qter),-13,-14,-15,-17, +
      18-18,der(18)(?),+21,+m1,+m2,+m3,+m4,+m5,+m6,+m7[cp25]. The different markers
      were identified by SKY analysis. Most of the cells carried 3-6 of these
      translocations: der(1;21), der(2;9;17), der(2;15;18), der(2;15;Y), der(8;10),
      der(10;17). Molecular examination using Neuroblastoma MLPA kit (MRC-Holland)
      revealed gain of 1q25, 1q42, 2q33, 2p23, 2p24 (N-myc), and 21q22, and loss of
      11q22, 11q23, 17p13, and 17q11. FISH analysis using N-myc probe showed high
      amplification levels of N-myc. The cytogenetic and molecular genetic work-ups
      revealed that the mandibular lesion is a metastasis of the original abdominal
      tumor and not a second primary caused by the aggressive treatment. Clinical
      parameters such as : patient's age, site of primary tumor and the mandibular
      metastasis, together with poor prognosis genetic markers explain the patient's
      short-term survival.

PMID- 22134670
TI  - Effect of substrate wettability in liquid dielectrophoresis (LDEP) based droplet
      generation: theoretical analysis and experimental confirmation.
AB  - The generation of droplets for biological reactions at the microscale can be
      achieved by many techniques, among which the so-called liquid dielectrophoresis
      technique (LDEP). This is not a new process, but the parameters influencing
      actuation voltage still need further insight: size and geometry (electrodes width
      and gap, dielectric thickness), materials (dielectric constant), liquids (surface
      tension, dielectric constant, conductivity), working conditions (voltage,
      frequency) and substrate wettability (contact angle). This large experimental
      space is firstly reduced using non dimensional numbers and then studied in a
      systematic way thanks to the design of experiments. The contact angle influence
      is explained thanks to a new analytical model. To summarize, this paper recalls
      analytical models used to predict the voltage threshold required to develop a
      liquid rivulet from a mother drop, taking the contact angle into account and
      providing a large set of experimental results.

PMID- 22134669
TI  - The clinical value of the novel cauterization procedure for the inferior
      turbinate artery during turbinate surgery.
AB  - The objective of the study was to evaluate the efficacy and the safety of the
      novel cauterization procedure of the inferior turbinate artery, which may be
      performed with any kind of inferior turbinate procedures in reducing the intra
      and the post-operative bleeding in partial inferior turbinectomy. A prospective
      controlled study was conducted in a referral center. Sixty patients (38M, 22F)
      who underwent partial turbinectomy were included. In 20 patients, partial
      turbinectomy was performed with the cauterization in one nasal cavity and the
      other one without it. The remaining 40 patients were divided into two groups
      which comprised cauterization positive and negative patients and are assessed in
      terms of post-operative bleeding. The area of the cauterization was 1 cm(2) field
      which is 1 cm anterior to the posterior attachment of the inferior turbinate on
      the lateral nasal wall, very close to the inferior turbinate, where the pulsating
      vessel is most commonly seen. Mean operation time, mean intra-operative blood
      loss and post-operative bleeding incidence are the main outcome measures. Post
      operative bleeding was seen in three patients (15%) in the cauterization negative
      group. No patient had post-operative bleeding in the cauterization positive
      group. Mean operation time and mean intra-operative bleeding amount were
      significantly lower in the cauterization positive side. Cauterization of the
      inferior turbinate artery on the lateral nasal wall is a safe and effective
      method which may also be performed with any kind of inferior turbinate procedures
      to reduce both the operation time and intra and post-operative bleeding.

PMID- 22134671
TI  - Dual-mode fluorescence switching of photochromic bisthiazolylcoumarin.
AB  - Three new photochromic coumarins were synthesized. Fluorescence of the open form
      of 7-hydroxy-3,4-bisthiazolyl-coumarin increased to 1400% by changing the pH only
      slightly from 6.05 to 7.58. This was subsequently quenched to 1.5% of the maximum
      intensity at the UV photostationary state in water-methanol media.

PMID- 22134672
TI  - LaTiO2N/In2O3 photoanodes with improved performance for solar water splitting.
AB  - LaTiO(2)N photoanodes for solar water splitting were prepared by electrophoretic
      deposition and demonstrated the best photocurrents ever reported for this
      material. Further important enhancement of the performance was obtained by the
      use of a sputtered In(2)O(3) overlayer.

PMID- 22134673
TI  - In vitro effect of adenosine A2A receptor antagonist SCH 442416 on the expression
      of glutamine synthetase and glutamate aspartate transporter in rat retinal Muller
      cells at elevated hydrostatic pressure.
AB  - The aim of this study was to investigate the effect of an adenosine A2A receptor
      antagonist on the expression of glutamine synthetase (GS) and glutamate aspartate
      transporter (GLAST) in rat retinal Muller cells at elevated hydrostatic pressure
      in vitro. Immunofluorescence staining of GS and GFAP was used for the
      identification of Muller cells. The expression of GS and GLAST in different
      hydrostatic pressure (0, 20, 40, 60, 80 mmHg/24 h) was examined by real-time PCR
      and Western blotting to identify the most suitable pressure. Muller cells treated
      with 0.1, 1, 10 uM SCH 442416 (A2A receptor antagonist) in the most suitable
      pressure, and the levels of GS and GLAST were examined by real-time PCR and
      Western blotting. Significantly increased expression of GS and GLAST at 40 mmHg
      pressure was observed in Muller cells and treatment with 10 uM SCH 442416 in 40
      mmHg pressure further promoted the expression of GS and GLAST. A2A receptor
      antagonist increased the expression of GLAST and GS of Muller cells and
      accelerated the clearance of extracellular glutamate.

PMID- 22134674
TI  - DSM-IV ADHD symptoms self-ratings by adolescents: test of invariance across
      gender.
AB  - OBJECTIVE: Measurement invariance deals with whether the expected scores on a
      measure are the same or different across different groups when the groups have
      the same level of the underlying latent trait scores. The study used multiple
      group confirmatory factor analysis (CFA) to examine measurement invariance across
      male and female adolescent self-ratings of the ADHD symptoms (recoded as binary
      scores). METHOD: To accomplish this, 178 male and 185 female adolescents, between
      12 and 17 years of age, completed an ADHD rating scale. RESULTS: For the
      measurement model, the results support the invariance for the configural model
      (same factor structure and the same items associated with the latent factors),
      metric invariance (same strength of the associations of items with the factors)
      for the factor loadings of 17 of the 18 symptoms, and all the error variances.
      For the construct model, there was invariance for the inattention (IA) and
      hyperactivity/impulsivity (HI) latent factor variances, covariances, and mean
      scores. Thus, there was good support for gender equivalency for the ADHD
      symptoms. CONCLUSION: These findings extend existing gender invariance data for
      the ADHD symptoms. The theoretical and clinical implications of the findings as
      well as the revision implications for Diagnostic and Statistical Manual of Mental
      Disorders (5th ed.; DSM-V) are discussed.

PMID- 22134675
TI  - A computer-assisted model for detection of MRI signs of Crohn's disease activity:
      future or fiction?
AB  - Magnetic resonance imaging is increasingly used for abdominal evaluation and is
      more and more considered as the optimal imaging technique for detection of mural
      inflammation in patients with Crohn's disease. Grading the disease activity is
      important in daily clinical practice to monitor the medical treatment and is
      assessed by evaluating different magnetic resonance imaging features.
      Unfortunately, only moderate interobserver agreement is reported for most of the
      subjective features and should be improved. A computer-assisted model for
      automatic detection of abnormalities, ability to grade disease severity, and
      thereby influence clinical disease management based on magnetic resonance imaging
      is missing. Recent techniques have focused on semi-automated methods for
      classification and segmentation of the bowel and also on objective measurement of
      bowel wall enhancement using absolute T1-values or dynamic contrast-enhanced
      imaging. This article reviews the available computerized techniques, as well as
      preferred developments.

PMID- 22134676
TI  - Viability and neural differentiation of mesenchymal stem cells derived from the
      umbilical cord following perinatal asphyxia.
AB  - OBJECTIVE: Hypoxia-ischemia is the leading cause of neurological handicaps in
      newborns worldwide. Mesenchymal stem cells (MSCs) collected from fresh cord blood
      of asphyxiated newborns have the potential to regenerate damaged neural tissues.
      The aim of this study was to examine the capacity for MSCs to differentiate into
      neural tissue that could subsequently be used for autologous transplantation.
      STUDY DESIGN: We collected cord blood samples from full-term newborns with
      perinatal hypoxemia (n=27), healthy newborns (n=14) and non-hypoxic premature
      neonates (n=14). Mononuclear cells were separated, counted, and then analyzed by
      flow cytometry to assess various stem cell populations. MSCs were isolated by
      plastic adherence and characterized by morphology. Cells underwent
      immunophenotyping and trilineage differentiation potential. They were then
      cultured in conditions favoring neural differentiation. Neural lineage commitment
      was detected using immunohistochemical staining for glial fibrillary acidic
      protein, tubulin III and oligodendrocyte marker O4 antibodies. RESULT:
      Mononuclear cell count and viability did not differ among the three groups of
      infants. Neural differentiation was best demonstrated in the cells derived from
      hypoxia-ischemia term neonates, of which 69% had complete and 31% had partial
      neural differentiation. Cells derived from preterm neonates had the least amount
      of neural differentiation, whereas partial differentiation was observed in only
      12%. CONCLUSION: These findings support the potential utilization of umbilical
      cord stem cells as a source for autologous transplant in asphyxiated neonates.

PMID- 22134677
TI  - Cost-effectiveness of childcare discounts on parent participation in preventive
      parent training in low-income communities.
AB  - We tested the cost-effectiveness of giving low-income parents childcare discounts
      contingent on their participation in the Chicago Parent Program, a 12-session
      preventive parent training (PT) program offered at their child's daycare center.
      Eight centers were matched and randomized to an experimental condition in which
      parents received a discount on their childcare bill (M = $8.92 per session
      attended) or a control group with no financial incentive. Participants (n = 174)
      consisted mostly of African American (55%) or Latino (42%) mothers, 62% reporting
      annual household incomes less than $20,000. Parents in the discount condition
      were 15.4% more likely to enroll than control parents, though this difference was
      not significant. There were no differences in PT attendance, parents' motivations
      for enrolling, or the degree to which parents were actively engaged in PT
      sessions by condition. Despite the added cost of the discounts, there was no
      difference in group costs by condition. Parent interviews revealed important
      challenges in implementing financial incentive programs in community-based
      agencies serving low-income families. Cost simulations show how low parent
      enrollment or low attendance negatively affect the economic efficiency of group
      based PT. Implications for policies guiding financial incentive programs
      targeting low-income families and their participation in prevention programs are
      discussed.

PMID- 22134678
TI  - Tough choices in tough times:  enhancing public health value in an era of
      declining resources.
AB  - The current economic recession is the deepest recession that the United States
      has experienced in more than 70 years. The convergence of severe economic
      conditions with the multiple population health and organizational challenges
      facing public health presents unprecedented demands on public health policymakers
      and executive leaders. This article reports a case study in which a Midwestern
      local health department intentionally realigned its structure and human resources
      to meet national public health accreditation standards while significantly
      reducing its budget in November 2010. The department transferred personal health
      care services that it previously provided to 3 federally qualified health centers
      in the community and reduced its workforce by 50%. The interrelated public policy
      and organizational management issues raised by the case study are reviewed, and
      questions and implications of the case for public health executive leaders,
      managers, policymakers, and researchers are identified.

PMID- 22134679
TI  - An alternative import pathway of AIF to the mitochondria.
AB  - In eukaryotic cells, transport of the newly synthesized proteins and
      phospholipids to the appropriate subcellular target compartments is essential for
      maintaining organelle morphology and cell survival. In animal cells, mitochondria
      are major organelles containing DNA genome that encodes only for a small fraction
      of their proteins, which are required for the organelle function. Most
      mitochondrial proteins are encoded by the nuclear genes and imported to the
      mitochondria following protein synthesis. Apoptosis-inducing factor (AIF), an
      essential FAD-dependent NADH oxidase for the oxidative phosphorylation, is
      located in the intermembranous space and contains mitochondrial localization
      signals. However, the import mechanism of AIF to the mitochondria is not yet
      studied. Using sucrose gradient ultracentrifugation and immunoblotting, AIF was
      detected in fractions of the endoplasmic reticulum, mitochondria-associated
      membranes (MAM) and mitochondria, and AIF from these fractions was resistant to
      trypsin in the absence of digitonin, suggesting that AIF could be protected by
      phospholipids. Knockdown of dynamin-related protein 1 (DRP1kd) expression reduced
      AIF levels in the mitochondria, but increased AIF concentrations in the MAM.
      Knockdown of mitofusin-2 (Mfn-2kd) or ATPase family AAA domain containing 3A
      (ATAD3Akd) expression, however, reduced AIF levels in the mitochondria and
      increased the number of transport vesicles that contained AIF in the cytosol,
      indicating that ATAD3A and Mfn-2 were respectively essential for the import and
      fusion of transport vesicles into the mitochondria. Here we show that AIF is
      imported from the endoplasmic reticulum to the mitochondria via mitochondria
      associated membranes and transport vesicles.

PMID- 22134681
TI  - Effects of different ion compositions on growth of obligately halophilic
      protozoan Halocafeteria seosinensis.
AB  - Substantial halophilic organisms have been found in 100-2000/00 salinities. These
      ranges represent a highly specialized halophilic environment to which only a few
      halotolerant species have adapted. Recent studies have underlined the existence
      of diverse obligately halophilic protozoa in the salinity ranges of 100-2000/00.
      The ranges of salinity under which these organisms can grow have been examined to
      some extent, but the balance of specific ions that will support growth has not
      been investigated. The heterotrophic nanoflagellate Halocafeteria, the type
      strain of which grows optimally at 1500/00 salinity and 35 degrees C, is a
      commonly encountered obligate halophile found in very hypersaline environments.
      These extreme environments can vary in their Mg:Ca ratios (i.e. weight ratios)
      and sulfate concentrations. To examine growth response of Halocafeteria to the
      different chemical compositions, densities of Halocafeteria seosinensis strain
      EHF34 were monitored in seven different ion composition media for 9 days at 1- to
      2-day intervals (at 1500/00 salinity and 35 degrees C, with no prey limitation).
      Halocafeteria does not grow at Mg:Ca ratios of 35 and 100 and at high sulfate
      concentrations of 11.6 and 31.6 g l(-1). It grows well in 0.6 g l(-1) sulfate
      media at Mg:Ca ratios of 2, 10 or 35, but not 100. The present study demonstrates
      that the growth of the obligate halophile Halocafeteria can be affected by
      different ion compositions in hypersaline environments. Therefore, Halocafeteria
      may not be ubiquitous in hypersaline environments due to its ionic requirements.

PMID- 22134680
TI  - Cyclodextrin glycosyltransferase: a key enzyme in the assimilation of starch by
      the halophilic archaeon Haloferax mediterranei.
AB  - A cyclodextrin glycosyltransferase (CGTase, EC 2.4.1.19) was successfully
      isolated and characterized from the halophilic archaeon Haloferax mediterranei.
      The enzyme is a monomer with a molecular mass of 77 kDa and optimum activity at
      55 degrees C, pH 7.5 and 1.5 M NaCl. The enzyme displayed many activities related
      to the degradation and transformation of starch. Cyclization was found to be the
      predominant activity, yielding a mixture of cyclodextrins, mainly alpha-CD,
      followed by hydrolysis and to a lesser extent coupling and disproportionation
      activities. Gene encoding H. mediterranei CGTase was cloned and heterologously
      overexpressed. Sequence analysis revealed an open reading frame of 2142 bp that
      encodes a protein of 713 amino acids. The amino acid sequence displayed high
      homology with those belonging to the alpha-amylase family. The CGTase is secreted
      to the extracellular medium by the Tat pathway. Upstream of the CGTase gene, four
      maltose ABC transporter genes have been sequenced (malE, malF, malG, malK). The
      expression of the CGTase gene yielded a fully active CGTase with similar kinetic
      behavior to the wild-type enzyme. The H. mediterranei CGTase is the first
      halophilic archaeal CGTase characterized, sequenced and expressed.

PMID- 22134682
TI  - Gellan gum capped silver nanoparticle dispersions and hydrogels: cytotoxicity and
      in vitro diffusion studies.
AB  - The preparation of highly stable water dispersions of silver nanoparticles using
      the naturally available gellan gum as a reducing and capping agent is reported.
      Further, exploiting the gel formation characteristic of gellan gum silver
      nanoparticle incorporated gels have also been prepared. The optical properties,
      morphology, zeta potential and long-term stability of the synthesized silver
      nanoparticles were investigated. The superior stability of the gellan gum-silver
      nanoparticle dispersions against pH variation and electrolyte addition is
      revealed. Finally, we studied the cytotoxicity of AgNP dispersions in mouse
      embryonic fibroblast cells (NIH3T3) and also evaluated the in vitro diffusion of
      AgNP dispersions/gels across rat skin.

PMID- 22134684
TI  - Inversions of chromosome arms 4AL and 2BS in wheat invert the patterns of chiasma
      distribution.
AB  - In many species, including wheat, crossing over is distal, and the proximal
      regions of chromosome arms contribute little to genetic maps. This was thought to
      be a consequence of terminal initiation of synapsis favoring distal crossing
      over. However, in an inverted rye chromosome arm, the pattern of metaphase I
      chiasmata was also inverted, suggesting that crossover frequencies were specific
      to chromosome segments. Here, wheat chromosome arms 2BS and 4AL, with essentially
      entire arms inverted in reverse tandem duplications (rtd), were studied in the MI
      of meiosis. Inversion-duplication placed the recombining segments in the middle
      of the arms. While the overall pairing frequencies of the inverted-duplicated
      arms were considerably reduced relative to normal arms, chiasmata, if present,
      were always located in the same regions as in structurally normal arms, and
      relative chiasma frequencies remained the same. The frequencies of fragment or
      fragment + bridge configurations in AI and AII indicated that of the two tandemly
      arranged copies of segments in rtds, the more distal inverted segments were more
      likely to cross over than the segments in their original orientations. These
      observations show that also in wheat, relative crossover frequencies along
      chromosome arms are predetermined and independent of the segment location. The
      segments normally not licensed to cross over do not do so even when placed in
      seemingly most favorable positions for it.

PMID- 22134683
TI  - Theranostic nanoplatforms for simultaneous cancer imaging and therapy: current
      approaches and future perspectives.
AB  - Theranostics is a concept which refers to the integration of imaging and therapy.
      As an evolving new field, it is related to but different from traditional imaging
      and therapeutics. It embraces multiple techniques to arrive at a comprehensive
      diagnostic, in vivo molecular images and an individualized treatment regimen.
      More recently, there is a trend of tangling these efforts with emerging materials
      and nanotechnologies, in an attempt to develop novel platforms and methodologies
      to tackle practical issues in clinics. In this article, topics of rationally
      designed nanoparticles for the simultaneous imaging and therapy of cancer will be
      discussed. Several exemplary nanoparticle platforms such as polymeric
      nanoparticles, gold nanomaterials, carbon nanotubes, magnetic nanoparticles and
      silica nanoparticles will be elaborated on and future challenges of nanoparticle
      based systems will be discussed.

PMID- 22134686
TI  - Nitrates and other nitric oxide donors in cardiology: current positioning and
      perspectives.
AB  - Nitric oxide donors have been commonly used in the therapy of cardiovascular
      disease for more than 150 years. In spite of this longevity and the popularity of
      their use, it appears somewhat paradoxical that there is no current consistent
      use among cardiologists, as to both their indications and their optimal mode of
      administration. In part this results from their contradictory pharmacodynamics:
      when given acutely, their effectiveness is undisputable; however, their long-term
      efficacy is potentially limited by the development of tolerance and the induction
      of endothelial dysfunction, which may have negative prognostic implications. This
      review reports recent biochemical and pathophysiological acquisitions, re
      examines the role of nitrates and other nitric oxide donors in cardiovascular
      medicine, comparing and commenting on international guidelines; and highlights
      areas of uncertainty, where more clinical research with these drugs would still
      be warranted.

PMID- 22134685
TI  - MAGE A1-A6 RT-PCR and MAGE A3 and p16 methylation analysis in induced sputum from
      patients with lung cancer and non-malignant lung diseases.
AB  - The melanoma antigen gene (MAGE) A1-A6 RT-PCR system was developed for the
      detection of lung cancer cells in the sputum. However, we identified MAGE
      expression in some patients with non-malignant lung diseases. To understand these
      patterns of MAGE expression, we performed MAGE A3 methylation-specific PCR (MSP)
      and p16 MSP. We collected 24 biopsy specimens of lung cancer tissue and performed
      MAGE A1-A6 RT-PCR, MAGE A3 MSP and p16 MSP. RNA and DNA were simultaneously
      extracted from induced sputum specimens of 133 patients with lung diseases and 30
      random sputum specimens of healthy individuals and the 3 molecular analyses were
      performed. The patients were diagnosed as 65 cases of lung cancer and 68 of
      benign lung diseases. Positive rates of MAGE A1-A6 RT-PCR, MAGE A3 MSP and p16
      MSP were as follows: in lung cancer tissue, 87.5, 58.3 and 70.8%; in the sputum
      of lung cancer patients, 50.8, 46.2 and 63.1%; benign lung diseases, 10.3, 30.9
      and 39.7%; and healthy individuals, 3.3, 6.7 and 3.3%. Of the 40 MAGE-positive
      cases, 33 were diagnosed with lung cancer and 7 as having benign lung diseases.
      From the 7 cases of MAGE-positive benign lung diseases, 6 cases showed
      methylation abnormalities. The MAGE-positive group revealed significantly higher
      rates of methylation abnormalities. Of the 40 MAGE-positive cases, 39 cases were
      found to be lung cancer or benign lung diseases with abnormal methylation. Thus,
      MAGE expression in the sputum suggests the presence of lung cancer cells or pre
      cancerous cells.

PMID- 22134687
TI  - Parylene to silicon nitride bonding for post-integration of high pressure
      microfluidics to CMOS devices.
AB  - High pressure-rated channels allow microfluidic assays to be performed on a
      smaller footprint while keeping the throughput, thanks to the higher enabled flow
      rates, opening up perspectives for cost-effective integration of CMOS chips to
      microfluidic circuits. Accordingly, this study introduces an easy, low-cost and
      efficient method for realizing high pressure microfluidics-to-CMOS integration.
      First, we report a new low temperature (280  degrees C) Parylene-C wafer bonding
      technique, where O(2) plasma-treated Parylene-C bonds directly to Si(3)N(4) with
      an average bonding strength of 23 MPa. The technique works for silicon wafers
      with a nitride surface and uses a single layer of Parylene-C deposited only on
      one wafer, and allows microfluidic structures to be easily formed by directly
      bonding to the nitride passivation layer of the CMOS devices. Exploiting this
      technology, we demonstrated a microfluidic chip burst pressure as high as 16 MPa,
      while metal electrode structures on the silicon wafer remained functional after
      bonding.

PMID- 22134688
TI  - Could dynamic ventilation waveforms bring about a paradigm shift in mechanical
      ventilation?

PMID- 22134689
TI  - Airways in smooth muscle alpha-actin null mice experience a compensatory
      mechanism that modulates their contractile response.
AB  - We hypothesized that ablation of smooth muscle alpha-actin (SM alpha-A), a
      contractile-cytoskeletal protein expressed in airway smooth muscle (ASM) cells,
      abolishes ASM shortening capacity and decreases lung stiffness. In both SM alpha
      A knockout and wild-type (WT) mice, airway resistance (Raw) determined by the
      forced oscillation technique rose in response to intravenous methacholine (Mch).
      However, the slope of Raw (cmH(2)O.ml(-1).s) vs. log(2) Mch dose (MUg.kg(-1).min(
      1)) was lower (P = 0.007) in mutant (0.54 +/- 0.14) than in WT mice (1.23 +/-
      0.19). RT-PCR analysis performed on lung tissues confirmed that mutant mice
      lacked SM alpha-A mRNA and showed that these mice had robust expressions of both
      SM gamma-A mRNA and skeletal muscle (SKM) alpha-A mRNA, which were not expressed
      in WT mice, and an enhanced SM22 mRNA expression relative to that in WT mice.
      Compared with corresponding spontaneously breathing mice, mechanical ventilation
      induced lung mechanical strain increased the expression of SM alpha-A mRNA in WT
      lungs; in mutant mice, it augmented the expressions of SM gamma-A mRNA and SM22
      mRNA and did not alter that of SKM alpha-A mRNA. In mutant mice, the expression
      of SM gamma-A mRNA in the lung during spontaneous breathing and its enhanced
      expression following mechanical ventilation are consistent with the likely
      possibility that in the absence of SM alpha-A, SM gamma-A underwent
      polymerization and interacted with smooth muscle myosin to produce ASM shortening
      during cholinergic stimulation. Thus our data are consistent with ASM in mutant
      mice experiencing compensatory mechanisms that modulated its contractile muscle
      capacity.

PMID- 22134690
TI  - Modeling mechanical strains and stresses in soft tissues of the shoulder during
      load carriage based on load-bearing open MRI.
AB  - Shoulder strain is a major limiting factor associated with load carriage. Despite
      advances in backpack designs, there are still reports of shoulder discomfort,
      loss of sensorimotor functions, and brachial plexus syndrome. The current study
      is aimed at characterizing mechanical loading conditions (strains and stresses)
      that develop within the shoulder's soft tissues when carrying a backpack. Open
      MRI scans were used for reconstructing a three-dimensional geometrical model of
      an unloaded shoulder and for measuring the soft tissue deformations caused by a
      25-kg backpack; subsequently, a subject-specific finite element (FE) model for
      nonlinear, large-deformation stress-strain analyses was developed. Skin pressure
      distributions under the backpack strap were used as reference data and for
      verifying the numerical solutions. The parameters of the model were adjusted to
      fit the calculated tissue deformations to those obtained by MRI. The MRI scans
      revealed significant compression of the soft tissues of the shoulder, with
      substantial deformations in the area of the subclavian muscle and the brachial
      plexus. The maximal pressure values exerted by a 25-kg load were substantial and
      reached ~90 kPa. In the muscle surrounding the brachial plexus, the model
      predicted maximal compressive strain of 0.14 and maximal tensile strain of 0.13,
      which might be injurious for the underlying neural tissue. In conclusion, the FE
      model provided some insights regarding the potential mechanisms underlying
      brachial plexus injuries related to load carriage. The large tissue deformations
      and pressure hotspots that were observed are likely to result in tissue damage,
      which may hamper neural function if sustained for long time exposures.

PMID- 22134691
TI  - Asymmetric deformation of contracting human gastrocnemius muscle.
AB  - Muscle fiber deformation is related to its cellular structure, as well as its
      architectural arrangement within the musculoskeletal system. While playing an
      important role in aponeurosis displacement, and efficiency of force transmission
      to the tendon, such deformation also provides important clues about the
      underlying mechanical structure of the muscle. We hypothesized that muscle fiber
      cross section would deform asymmetrically to satisfy the observed constant volume
      of muscle during a contraction. Velocity-encoded, phase-contrast, and
      morphological magnetic resonance imaging techniques were used to measure changes
      in fascicle length, pinnation angle, and aponeurosis separation of the human
      gastrocnemius muscle during passive and active eccentric ankle joint movements.
      These parameters were then used to subsequently calculate the in-plane muscle
      area subtended by the two aponeuroses and fascicles and to calculate the in-plane
      (dividing area by fascicle length), and through-plane (dividing muscle volume by
      area) thicknesses. Constant-volume considerations of the whole-muscle geometry
      require that, as fascicle length increases, the muscle fiber cross-sectional area
      must decrease in proportion to the length change. Our empirical findings confirm
      the definition of a constant-volume rule that dictates that changes in the
      dimension perpendicular to the plane, i.e., through-plane thickness, (-6.0% for
      passive, -3.3% for eccentric) equate to the reciprocal of the changes in area
      (6.8% for passive, 3.7% for eccentric) for both exercise paradigms. The asymmetry
      in fascicle cross-section deformation for both passive and active muscle fibers
      is established in this study with a ~22% in-plane and ~6% through-plane fascicle
      thickness change. These fiber deformations have functional relevance, not only
      because they affect the force production of the muscle itself, but also because
      they affect the characteristics of adjacent muscles by deflecting their line of
      pull.

PMID- 22134692
TI  - Cerebrovascular and corticomotor function during progressive passive hyperthermia
      in humans.
AB  - The present study examined the integrative effects of passive heating on cerebral
      perfusion and alterations in central motor drive. Eight participants underwent
      passive hyperthermia [0.5 degrees C increments in core temperature (Tc) from
      normothermia (37 +/- 0.3 degrees C) to their limit of thermal tolerance (T-LIM;
      39.0 +/- 0.4 degrees C)]. Blood flow velocity in the middle cerebral artery
      (CBFv) and respiratory responses were measured continuously. Arterial blood gases
      and blood pressure were obtained intermittently. At baseline and each Tc level,
      supramaximal femoral nerve stimulation and transcranial magnetic stimulation
      (TMS) were performed to assess neuromuscular and cortical function, respectively.
      At T-LIM, measures were (in a randomized order) also made during a period of
      breathing 5% CO(2) gas to restore eucapnia (+5% CO(2)). Mean heating time was 179
      +/- 51 min, with each 0.5 degrees C increment in Tc taking 40 +/- 10 min. CBFv
      was reduced by ~20% below baseline from +0.5 degrees C until T-LIM. Maximal
      voluntary contraction (MVC) of the knee extensors was decreased at T-LIM (-9 +/-
      10%; P < 0.05), and cortical voluntary activation (VA), assessed by TMS, was
      decreased at +1.5 degrees C and T-LIM by 11 +/- 8 and 22 +/- 23%, respectively (P
      < 0.05). Corticospinal excitability (measured as the EMG response produced by
      TMS) was unaltered. Reductions in cortical VA were related to changes in
      ventilation (Ve; R(2) = 0.76; P < 0.05) and partial pressure of end-tidal CO(2)
      (Pet(CO(2)); R(2) = 0.63; P < 0.05) and to changes in CBFv (R(2) = 0.61; P =
      0.067). Interestingly, although CBFv was not fully restored, MVC and cortical VA
      were restored towards baseline values during inhalation of 5% CO(2). These
      results indicate that descending voluntary drive becomes progressively impaired
      as Tc is increased, presumably due, in part, to reductions in CBFv and to
      hyperthermia-induced hyperventilation and subsequent hypocapnia.

PMID- 22134693
TI  - Acute running stimulates hippocampal dopaminergic neurotransmission in rats, but
      has no influence on brain-derived neurotrophic factor.
AB  - Hippocampal brain-derived neurotrophic factor (BDNF) protein is increased with
      exercise in rats. Monoamines seem to play a role in the regulation of BDNF, and
      monoamine neurotransmission is known to increase with exercise. The purpose of
      this study was to examine the influence of acute exercise on monoaminergic
      neurotransmission and BDNF protein concentrations. Hippocampal microdialysis was
      performed in rats that were subjected to 60 min of treadmill running at 20 m/min
      or rest. Two hours postexercise, the rats were killed, and the hippocampus was
      dissected. In experiments without microdialysis, hippocampus and serum samples
      were collected immediately after exercise. Exercise induced a twofold increase in
      hippocampal dopamine release. Noradrenaline and serotonin release were not
      affected. Hippocampal BDNF levels were not influenced, whether they were measured
      immediately or 2 h after the exercise protocol. Serum BDNF levels did not change
      either, but serum BDNF was negatively correlated to peripheral corticosterone
      concentrations, indicating a possible inhibitory reaction to the stress of
      running. Sixty minutes of exercise enhances dopamine release in the hippocampus
      of the rat in vivo. However, this increase is not associated with changes in BDNF
      protein levels immediately nor 2 h after the acute exercise bout. An increased
      corticosterone level might be the contributing factor for the absence of changes
      in BDNF.

PMID- 22134694
TI  - Human muscle length-dependent changes in blood flow.
AB  - Although a multitude of factors that influence skeletal muscle blood flow have
      been extensively investigated, the influence of muscle length on limb blood flow
      has received little attention. Thus the purpose of this investigation was to
      determine if cyclic changes in muscle length influence resting blood flow. Nine
      healthy men (28 +/- 4 yr of age) underwent a passive knee extension protocol
      during which the subjects' knee joint was passively extended and flexed through
      100-180 degrees  knee joint angle at a rate of 1 cycle per 30 s. Femoral blood
      flow, cardiac output (CO), heart rate (HR), stroke volume (SV), and mean arterial
      pressure (MAP) were continuously recorded during the entire protocol. These
      measurements revealed that slow passive changes in knee joint angle did not have
      a significant influence on HR, SV, MAP, or CO; however, net femoral blood flow
      demonstrated a curvilinear increase with knee joint angle (r(2) = 0.98) such that
      blood flow increased by ~90% (125 ml/min) across the 80 degrees  range of motion.
      This net change in blood flow was due to a constant antegrade blood flow across
      knee joint angle and negative relationship between retrograde blood flow and knee
      joint angle (r(2) = 0.98). Thus, despite the absence of central hemodynamic
      changes and local metabolic factors, blood flow to the leg was altered by changes
      in muscle length. Therefore, when designing research protocols, researchers need
      to be cognizant of the fact that joint angle, and ultimately muscle length,
      influence limb blood flow.

PMID- 22134695
TI  - The curious case of anabolic resistance: old wives' tales or new fables?

PMID- 22134696
TI  - Mechanical effect of rat flexor carpi ulnaris muscle after tendon transfer: does
      it generate a wrist extension moment?
AB  - The mechanical effect of a muscle following agonist-to-antagonist tendon
      transfers does not always meet the surgeon's expectations. We tested the
      hypothesis that after flexor carpi ulnaris (FCU) to extensor carpi radialis (ECR)
      tendon transfer in the rat, the direction (flexion or extension) of the muscle's
      joint moment is dependent on joint angle. Five weeks after recovery from surgery
      (tendon transfer group) and in a control group, wrist angle-moment
      characteristics of selectively activated FCU muscle were assessed for progressive
      stages of dissection: 1) with minimally disrupted connective tissues, 2) after
      distal tenotomy, and 3) after maximal tendon and muscle belly dissection, but
      leaving blood supply and innervations intact. In addition, force transmission
      from active FCU onto the distal tendon of passive palmaris longus (PL) muscle (a
      wrist flexor) was assessed. Excitation of control FCU yielded flexion moments at
      all wrist angles tested. Tenotomy decreased peak FCU moment substantially (by
      93%) but not fully. Only after maximal dissection, FCU wrist moment became
      negligible. The mechanical effect of transferred FCU was bidirectional: extension
      moments in flexed wrist positions and flexion moments in extended wrist
      positions. Tenotomy decreased peak extension moment (by 33%) and increased peak
      flexion moment of transferred FCU (by 41%). Following subsequent maximal FCU
      dissection, FCU moments decreased to near zero at all wrist angles tested. We
      confirmed that, after transfer of FCU towards a wrist extensor insertion, force
      can be transmitted from active FCU to the distal tendon of passive PL. We
      conclude that mechanical effects of a muscle after tendon transfer to an
      antagonistic site can be quite different from those predicted based solely on the
      sign of the new moment arm at the joint.

PMID- 22134697
TI  - Respiratory effect of the lower rib displacement produced by the diaphragm.
AB  - The diaphragm acting alone causes a cranial displacement of the lower ribs and a
      caudal displacement of the upper ribs. The respiratory effect of the lower rib
      displacement, however, is uncertain. In the present study, two sets of
      experiments were performed in dogs to assess this effect. In the first, all the
      inspiratory intercostal muscles were severed, so that the diaphragm was the only
      muscle active during inspiration, and the normal inspiratory cranial displacement
      of the lower ribs was suppressed at regular intervals. In the second experiment,
      the animals were given a muscle relaxant to abolish respiratory muscle activity,
      and external, cranially oriented forces were applied to the lower rib pairs to
      simulate the action of the diaphragm on these ribs. The data showed that 1)
      holding the lower ribs stationary during spontaneous, isolated diaphragm
      contraction had no effect on the change in lung volume during unimpeded
      inspiration and no effect on the fall in pleural pressure (Ppl) during occluded
      breaths; 2) the procedure, however, caused an increase in the caudal displacement
      of the upper ribs; and 3) pulling the lower rib pairs cranially induced a cranial
      displacement of the upper ribs and a small fall in Ppl. These observations
      indicate that the force applied on the lower ribs by the diaphragm during
      spontaneous contraction, acting through the interdependence of the ribs, is
      transmitted to the upper ribs and has an inspiratory effect on the lung. However,
      this effect is very small compared to that of the descent of the dome.

PMID- 22134698
TI  - Effects of seasonal vitamin D deficiency and respiratory acidosis on bone
      metabolism markers in submarine crewmembers during prolonged patrols.
AB  - The aim of the study was to determine the seasonal influence of vitamin D status
      on bone metabolism in French submariners over a 2-mo patrol. Blood samples were
      collected as follows: prepatrol and patrol days 20, 41, and 58 on crewmembers
      from both a winter (WP; n = 20) and a summer patrol (SP; n = 20), respectively.
      Vitamin D status was evaluated for WP and SP. Moreover, extended parameters for
      acid-base balance (Pco(2), pH, and bicarbonate), bone metabolism (bone alkaline
      phosphatase and COOH-terminal telopeptide of type I collagen), and mineral
      homeostasis (parathyroid hormone, ionized calcium and phosphorus) were
      scrutinized. As expected, SP vitamin D status was higher than WP vitamin D
      status, regardless of the considered experimental time. A mild chronic
      respiratory acidosis (CRA) was identified in both SP and WP submariners, up to
      patrol day 41. Such an occurrence paired up with an altered bone remodeling
      coupling (decreased bone alkaline phosphatase-to-COOH-terminal telopeptide of
      type I collagen ratio). At the end of the patrol (day 58), a partial compensation
      of CRA episode, combined with a recovered normal bone remodeling coupling, was
      observed in SP, not, however, in WP submariners. The mild CRA episode displayed
      over the initial 41-day submersion period was mainly induced by a hypercapnia
      resulting from the submarine-enriched CO(2) level. The correlated impaired bone
      remodeling may imply a physiological attempt to compensate this acidosis via bone
      buffering. On patrol day 58, the discrepancy observed in terms of CRA
      compensation between SP and WP may result from the seasonal influence on vitamin
      D status.

PMID- 22134699
TI  - Cardiovascular regulation during long-duration spaceflights to the International
      Space Station.
AB  - Early evidence from long-duration flights indicates general cardiovascular
      deconditioning, including reduced arterial baroreflex gain. The current study
      investigated the spontaneous baroreflex and markers of cardiovascular control in
      six male astronauts living for 2-6 mo on the International Space Station.
      Measurements were made from the finger arterial pressure waves during spontaneous
      breathing (SB) in the supine posture pre- and postflight and during SB and paced
      breathing (PB, 0.1 Hz) in a seated posture pre- and postflight, as well as early
      and late in the missions. There were no changes in preflight measurements of
      heart rate (HR), blood pressure (BP), or spontaneous baroreflex compared with in
      flight measurements. There were, however, increases in the estimate of left
      ventricular ejection time index and a late in-flight increase in cardiac output
      (CO). The high-frequency component of RR interval spectral power, arterial pulse
      pressure, and stroke volume were reduced in-flight. Postflight there was a small
      increase compared with preflight in HR (60.0 +/- 9.4 vs. 54.9 +/- 9.6 beats/min
      in the seated posture, P < 0.05) and CO (5.6 +/- 0.8 vs. 5.0 +/- 1.0 l/min, P <
      0.01). Arterial baroreflex response slope was not changed during spaceflight,
      while a 34% reduction from preflight in baroreflex slope during postflight PB was
      significant (7.1 +/- 2.4 vs. 13.4 +/- 6.8 ms/mmHg), but a smaller average
      reduction (25%) during SB (8.0 +/- 2.1 vs. 13.6 +/- 7.4 ms/mmHg) was not
      significant. Overall, these data show no change in markers of cardiovascular
      stability during long-duration spaceflight and only relatively small changes
      postflight at rest in the seated position. The current program routine of
      countermeasures on the International Space Station provided sufficient stimulus
      to maintain cardiovascular stability under resting conditions during long
      duration spaceflight.

PMID- 22134700
TI  - Novel whole body plethysmography system for the continuous characterization of
      sleep and breathing in a mouse.
AB  - Sleep is associated with marked alterations in ventilatory control that lead to
      perturbations in respiratory timing, breathing pattern, ventilation, pharyngeal
      collapsibility, and sleep-related breathing disorders (SRBD). Mouse models offer
      powerful insight into the pathogenesis of SRBD; however, methods for obtaining
      the full complement of continuous, high-fidelity respiratory,
      electroencephalographic (EEG), and electromyographic (EMG) signals in
      unrestrained mice during sleep and wake have not been developed. We adapted whole
      body plethysmography to record EEG, EMG, and respiratory signals continuously in
      unrestrained, unanesthetized mice. Whole body plethysmography tidal volume and
      airflow signals and a novel noninvasive surrogate for respiratory effort
      (respiratory movement signal) were validated against simultaneously measured gold
      standard signals. Compared with the gold standard, we validated 1) tidal volume
      (correlation, R(2) = 0.87, P < 0.001; and agreement within 1%, P < 0.001); 2)
      inspiratory airflow (correlation, R(2) = 0.92, P < 0.001; agreement within 4%, P
      < 0.001); 3) expiratory airflow (correlation, R(2) = 0.83, P < 0.001); and 4)
      respiratory movement signal (correlation, R(2) = 0.79-0.84, P < 0.001). The
      expiratory airflow signal, however, demonstrated a decrease in amplitude compared
      with the gold standard. Integrating respiratory and EEG/EMG signals, we fully
      characterized sleep and breathing patterns in conscious, unrestrained mice and
      demonstrated inspiratory flow limitation in a New Zealand Obese mouse. Our
      approach will facilitate studies of SRBD mechanisms in inbred mouse strains and
      offer a powerful platform to investigate the effects of environmental and
      pharmacological exposures on breathing disturbances during sleep and wakefulness.

PMID- 22134701
TI  - Inhibition of ROS-activated ERK1/2 pathway contributes to the protection of H2S
      against chemical hypoxia-induced injury in H9c2 cells.
AB  - Hydrogen sulfide (H(2)S) has been shown to exert cardioprotective effects.
      However, the roles of extracellular signal-regulated protein kinases 1/2 (ERK1/2)
      in H(2)S-induced cardioprotection have not been completely elucidated. In this
      study, cobalt chloride (CoCl(2)), a chemical hypoxia mimetic agent, was applied
      to treat H9c2 cells to establish a chemical hypoxia-induced cardiomyocyte injury
      model. The results showed that pretreatment with NaHS (a donor of H(2)S) before
      exposure to CoCl(2) attenuated the decreased cell viability, the increased
      apoptosis rate, the loss of mitochondrial membrane potential (DeltaPsim), and the
      intracellular accumulation of reactive oxygen species (ROS) in H9c2 cells.
      Exposure of H9c2 cells to CoCl(2) or hydrogen peroxide (H(2)O(2)) upregulated
      expression of phosphorylated (p) ERK1/2, which was reduced by pretreatment with
      NaHS or N-acetyl-L-cysteine, a ROS scavenger. More importantly, U0126, a
      selective inhibitor of ERK1/2, mimicked the above cytoprotection of H(2)S against
      CoCl(2)-induced injury in H9c2 cells. In conclusion, these results indicate that
      H(2)S protects H9c2 cells against chemical hypoxia-induced injury partially by
      inhibiting ROS-mediated activation of ERK1/2.

PMID- 22134703
TI  - Molecular mapping of the regenerative niche in a murine model of myocardial
      infarction.
AB  - Adult stem cells are distributed through the whole organism, and present a great
      potential for the therapy of different types of disease. For the design of
      efficient therapeutic strategies, it is important to have a more detailed
      understanding of their basic biological characteristics, as well as of the
      signals produced by damaged tissues and to which they respond. Myocardial
      infarction (MI), a disease caused by a lack of blood flow supply in the heart,
      represents the most common cause of morbidity and mortality in the Western world.
      Stem cell therapy arises as a promising alternative to conventional treatments,
      which are often ineffective in preventing loss of cardiomyocytes and fibrosis.
      Cell therapy protocols must take into account the molecular events that occur in
      the regenerative niche of MI. In the present study, we investigated the
      expression profile of ten genes coding for chemokines or cytokines in a murine
      model of MI, aiming at the characterization of the regenerative niche. MI was
      induced in adult C57BL/6 mice and heart samples were collected after 24 h and 30
      days, as well as from control animals, for quantitative RT-PCR. Expression of the
      chemokine genes CCL2, CCL3, CCL4, CCL7, CXCL2 and CXCL10 was significantly
      increased 24 h after infarction, returning to baseline levels on day 30.
      Expression of the CCL8 gene significantly increased only on day 30, whereas gene
      expression of CXCL12 and CX3CL1 were not significantly increased in either
      ischemic period. Finally, expression of the IL-6 gene increased 24 h after
      infarction and was maintained at a significantly higher level than control
      samples 30 days later. These results contribute to the better knowledge of the
      regenerative niche in MI, allowing a more efficient selection or genetic
      manipulation of cells in therapeutic protocols.

PMID- 22134702
TI  - Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance:
      potential involvement of Akt and ERK signalings.
AB  - The present study explored the effects of thyroid hormone (TH) treatment on post
      ischemic cardiac function and potential implicated mechanisms. Acute myocardial
      infarction (AMI) was induced in mice by coronary artery ligation while sham
      operated animals served as controls. This procedure resulted in a marked
      depression of cardiac function and significant reduction in TH levels in plasma.
      TH was given at a dose aiming to normalize T3 levels in plasma [AMI-TH (A)] and
      also at higher doses. The group of animals treated with the highest dose of TH,
      which displayed significantly increased mortality rate was included in the study
      [AMI-TH (B)]. In AMI-TH (A) mice, TH significantly improved left ventricular (LV)
      ejection fraction (EF%), [27.9% (1.4) in AMI versus 38.0 (3.1) in AMI-TH (A), P <
      0.05], and favorably remodeled LV chamber while alpha-MHC was the dominant
      isoform expressed. In AMI-TH (B) mice, TH treatment resulted in increased
      mortality as compared to untreated mice (73% vs 47%, P < 0.05), while the
      favorable effect of TH was not evident in the survived animals. At the molecular
      level, TH, at the replacement dose, modestly increased p-Akt levels in the
      myocardium without any change in p-ERK levels. On the contrary, TH at the higher
      dose resulted in further increase in p-Akt along with an increase in p-ERK
      levels. In conclusion, TH appears to have a dose-dependent bimodal effect on post
      ischemic cardiac performance and this effect may, at least in part, be mediated
      by a distinct pattern of activation of Akt and ERK signaling.

PMID- 22134704
TI  - Analysis of the Fragile X mental retardation protein isoforms 1, 2 and 3
      interactions with the G-quadruplex forming semaphorin 3F mRNA.
AB  - Fragile X syndrome, the most prevalent inheritable mental retardation, is caused
      by the loss of fragile X mental retardation protein (FMRP) expression. FMRP is an
      RNA-binding protein with nucleo-cytoplasmic shuttle activity, proposed to act as
      a translation regulator of specific mRNAs in the brain. It has been shown that
      FMRP uses its arginine-glycine-glycine (RGG) box domain to bind a subset of mRNA
      targets that form a G-quadruplex structure. FMRP has also been shown to undergo
      the post-translational modifications of arginine methylation and phosphorylation,
      as well as alternative splicing, resulting in multiple isoforms. The alternative
      splice isoforms investigated in this study, isoform 1 (ISO1), isoform 2 (ISO2),
      and isoform 3 (ISO3), are created by the alternative splicing acceptor site at
      exon 15. FMRP ISO2 and ISO3 are truncated by 12 and 13 residues, respectively,
      relative to the longest FMRP isoform ISO1. These truncations, which are in the
      close proximity of the RGG box domain, preserve the integrity of the RGG box in
      all three isoforms, but eliminate the in vivo phosphorylation sites, present only
      on FMRP ISO1. We have expressed and purified recombinant FMRP ISO1, ISO2 and ISO3
      in Escherichia coli, free of post-translational modifications, and by using
      fluorescence spectroscopy, we show that each FMRP isoform binds G-quadruplex RNA,
      albeit with different binding affinities, suggesting that naturally occurring
      sequence modifications in the proximity of the RGG box modulate its G-quadruplex
      RNA binding ability.

PMID- 22134705
TI  - Strategies in biomimetic surface engineering of nanoparticles for biomedical
      applications.
AB  - Engineered nanoparticles (NPs) play an increasingly important role in biomedical
      sciences and in nanomedicine. Yet, in spite of significant advances, it remains
      difficult to construct drug-loaded NPs with precisely defined therapeutic
      effects, in terms of release time and spatial targeting. The body is a highly
      complex system that imposes multiple physiological and cellular barriers to
      foreign objects. Upon injection in the blood stream or following oral
      administation, NPs have to bypass numerous barriers prior to reaching their
      intended target. A particularly successful design strategy consists in masking
      the NP to the biological environment by covering it with an outer surface
      mimicking the composition and functionality of the cell's external membrane. This
      review describes this biomimetic approach. First, we outline key features of the
      composition and function of the cell membrane. Then, we present recent
      developments in the fabrication of molecules that mimic biomolecules present on
      the cell membrane, such as proteins, peptides, and carbohydrates. We present
      effective strategies to link such bioactive molecules to the NPs surface and we
      highlight the power of this approach by presenting some exciting examples of
      biomimetically engineered NPs useful for multimodal diagnostics and for target
      specific drug/gene delivery applications. Finally, critical directions for future
      research and applications of biomimetic NPs are suggested to the readers.

PMID- 22134706
TI  - The sex specificity of hip-joint muscles offers an explanation for better results
      in men after total hip arthroplasty.
AB  - PURPOSE: Choosing a surgical approach for total hip arthroplasty (THA) has a
      patient-specific impact on peri-operative muscle damage as well as postoperative
      functional outcome. Women and aged patients increasingly benefit from minimally
      invasive surgical procedures. For this reason, and due to the distinctly
      different bony anatomy of men and women, the hypothesis of this study is that
      muscle distribution around the hip joint is dependent on sex and age. The goal of
      this study was to analyse hip musculature in men and women and to correlate total
      muscle volume distribution. METHODS: From 93 computed tomography (CT) scans of
      the pelvis (45 men, 48 women) volumes of gluteus medius (GMV), gluteus maximus
      (GXV) and tensor faciae latae (TFL) muscles were measured on both sides of the
      pelvis. The distribution of muscle volumes was normalised to patient weight and
      then correlated with sex and age. RESULTS: The measured muscle volumes featured
      no major differences between the left and the right side. The absolute total
      volume of the hip-encompassing muscular system (TMV) is bigger in men than in
      women. Correlations between TMV and collected data were observed in both sexes in
      relation to body weight and size (men p < .00001; women p 0.001). With increased
      body weight, the TMV of the male patients increased progressively (women 11.2 cm
      TMV/kg KG vs. men 17.4 cm TMV/kg KG) (p 0.04). The relative distribution of each
      muscle volume (GMV, GXV, TFL) around the hip joint showed no major differences
      with respect to sex and/or age (p 0.986 and 0.996, respectively). CONCLUSIONS:
      The equal relative muscle distribution in men and women around the hip joint
      reflects neither sex-related differences observed in clinical outcomes after THA
      nor bony anatomy. Yet men exhibited more muscle reserves (muscle volume; absolute
      and in relation to body mass) , which could explain the better outcome in men
      after THA. Furthermore, this suggests the extraordinary importance of muscle
      sparing surgical approaches in women. The results represent the rationale for
      designing and analysing future studies of sex-specific therapies with regard to
      hip-joint muscles.

PMID- 22134707
TI  - Pathological gait in children with Legg-Calve-Perthes disease and proposal for
      gait modification to decrease the hip joint loading.
AB  - PURPOSE: Legg-Calve-Perthes disease (LCP) severely limits the range of hip motion
      and hinders a normal gait. Loading of the hip joint is a major consideration in
      LCP treatment. The aim of this study was to evaluate gait patterns in LCP and
      identify gait modifications to decrease the load on the affected hip. METHODS:
      Forty children with unilateral LCP were divided into three groups based on the
      time base integral of the hip abductor moments during single stance on the
      affected side acquired during instrumented 3D gait analysis. X-rays of the
      affected hip were classified according to Herring and Catterall. RESULTS:
      Children in the "unloading" group spontaneously adopted a Duchenne-like gait with
      pelvis elevation, hip abduction and external rotation during single support
      phase. The "normal-loading" group showed pelvis elevation with a neutral hip
      position in the frontal plane. In the "overloading" group the pelvis dropped to
      the swinging limb at the beginning of stance accompanied by prolonged hip
      adduction. The time base integral of the hip abductor moments during single
      stance correlated positively with the X-ray classifications of Herring and
      Catterall, hip abduction angle and age. Older children preferred to walk in hip
      adduction during single stance, had more impaired hips and tended to overload
      them. CONCLUSION: The hip overloading pattern should be avoided in children with
      LCP. Gait training to unload the hip might become an integral component of
      conservative treatment in children with LCP.

PMID- 22134708
TI  - Higher BMP receptor expression and BMP-2-induced osteogenic differentiation in
      tendon-derived stem cells compared with bone-marrow-derived mesenchymal stem
      cells.
AB  - PURPOSE: Surgical reattachment of tendon to bone often fails due to regeneration
      failure of the specialised tendon-bone junction (TBJ). The use of mesenchymal
      stem cells for TBJ regeneration has been reported with promising results. Tendon
      derived stem cells (TDSCs) with high proliferative and multi-lineage
      differentiation potential have been isolated. As stem cells residing in tendons,
      TDSCs can be considered a new cell source for TBJ repair. Bone morphogenic
      protein 2 (BMP-2) is a potent osteogenic factor with roles in normal bone healing
      and pathological ectopic bone formation in soft tissues. The use of BMP-2 to
      promote TBJ repair has been well reported. This study aimed to compare TDSCs to
      the gold standard bone-marrow-derived mesenchymal stem cells (BMSCs) with respect
      to osteogenic response to BMP-2 in vitro. METHOD: The clonogenicity and multi
      differentiation potential of TDSCs and BMSCs were identified by colony-forming
      unit assay, osteogenic, adipogenic and chondrogenic differentiation assays. Their
      osteogenic response to BMP-2 in vitro was examined by alkaline phosphatase (ALP)
      cytochemical staining, ALP activity assay and Alizarin red S staining of calcium
      nodule formation. Messenger RNA (mRNA) and BMP receptor (types IA, IB and II)
      protein expression were examined by quantitative real-time reverse-transcriptase
      polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: Our results
      showed that both TDSCs and BMSCs exhibited stem cell properties, including
      clonogenicity and multi-differentiation potential. TDSCs expressed higher mRNA
      and protein levels of BMP receptors IA, IB and II. They also exhibited higher
      osteogenic differentiation with and without BMP-2 stimulation compared with
      BMSCs. CONCLUSIONS: TDSCs with/without BMP-2 might be an attractive source for
      TBJ repair compared with BMSCs.

PMID- 22134709
TI  - Spondylodiscitis in patients under haemodyalisis.
AB  - PURPOSE: The purpose of this study was to reach conclusions about the diagnosis
      and treatment of a series of patients with spondylodiscitis under haemodialysis
      treatment. METHODS: We collected and studied 23 patients included in a
      prospective database from two neighbouring hospitals. Descriptive statistical
      analysis was performed. RESULTS: The diagnosis was frequently made very late and
      early negative cultures were not uncommon; magnetic resonance images allowed for
      an early diagnosis with accurate anatomical information. Empirical antibiotic
      treatment with prompt surgery produced good results in patients under risk of, or
      having neurological problems. Surgical approaches did not differ from pyogenic or
      tuberculous spondylodiscitis. Age in our series was not a predictive issue.
      CONCLUSIONS: Whenever a patient under haemodialysis has symptoms of spinal
      disease, particularly back pain with fever, they should undergo an MRI. If
      diagnosis of spondylodiscitis is made prompt empirical antibiotherapy should be
      instituted. Blood cultures should be performed and tissue samples taken for
      cultures; however, culture outcome must not delay therapy. Early surgical
      decompression leads to good results.

PMID- 22134710
TI  - A near-infrared fluorescent probe for monitoring ozone and imaging in living
      cells.
AB  - A near-infrared fluorescent probe (Trp-Cy) for endogenous ozone is presented,
      which exhibited a large stokes shift about 140 nm and a rapid fluorescence
      response to ozone with high selectivity and sensitivity.

PMID- 22134711
TI  - Novel heterometal-organic complexes as first single source precursors for up
      converting NaY(Ln)F4 (Ln = Yb, Er, Tm) nanomaterials.
AB  - First heterometal-organic single source precursors for NaYF(4) nanomaterials as a
      host matrix for up-conversion emission are reported. These novel heterobimetallic
      derivatives NaY(TFA)(4)(diglyme) (1), [Na(triglyme)(2)][Y(2)(TFA)(7)(THF)(2)] (2)
      and Na(2)Y(TFA)(5)(tetraglyme) (3) (TFA = trifluoroacetate), which were fully
      characterized by elemental analysis, FT-IR and (1)H NMR spectroscopy, TG-DTA data
      as well as single crystal X-ray structures, are advantageous in terms of being
      anhydrous and having lower decomposition temperatures in comparison to the
      homometallic precursor Y(TFA)(3)(H(2)O)(3). In addition, they also contain
      chelating glyme ligands, which act as capping reagents during decomposition to
      control the NaYF(4) particle size and render them monodisperse in organic
      solvents. On decomposition in 1-octadecene, the molecular derivatives 1 and 3 are
      converted, in the absence of any surfactant or capping reagent, to cubic NaYF(4)
      nanocrystals at significantly lower temperatures (below 250  degrees C). At
      higher temperature, a mixture of the cubic and hexagonal phases was obtained, the
      relative ratio of the two phases depending on the reaction temperature. A pure
      hexagonal phase, which is many folds more efficient for UC emission than the
      cubic phase, was obtained by calcining nanocrystals of mixed phase at 400 
      degrees C. In order to co-dope this host matrix with up-converting lanthanide
      cations, analogous complexes NaLn(TFA)(4)(diglyme) [Ln = Er (4), Tm (5), Yb (6)]
      and Na(2)Ln(TFA)(5)(tetraglyme) [Ln = Er (7), Yb (8)] were also prepared and
      characterized. The decomposition in 1-octadecene of suitable combinations and
      appropriate molar ratios of these yttrium, ytterbium and erbium/thulium
      derivatives gave cubic and/or hexagonal NaYF(4): Yb(3+), Er(3+)/Tm(3+)
      nanocrystals (NCs) capped by diglyme or tetraglyme ligands, which were
      characterized by IR, TG-DTA data, EDX analysis and TEM studies. Surface
      modification of these NCs by ligand exchange reactions with poly acrylic acid
      (PAA) and polyethyleneglycol (PEG) diacid 600 was also carried out to render them
      water soluble. The THF solutions of suitable combinations of the diglyme
      derivatives were also used to elaborate the thin films of NaYF(4):Yb(3+),
      Er(3+)/Tm(3+) on a glass or Si wafer substrate by spin coating. The multicolour
      up-conversion fluorescence was successfully realized in the Yb(3+)/Er(3+)
      (green/red) and Yb(3+)/Tm(3+) (blue/violet) co-doped NaYF(4) nanoparticles and
      thin films, which demonstrates that they are promising UC nanophosphors of
      immense practical interest. The up-conversion excitation pathways for the
      Er(3+)/Yb(3+) and Tm(3+)/Yb(3+) co-doped materials are discussed.

PMID- 22134712
TI  - Colored perfluorocarbon liquids as novel intraoperative tools.
AB  - BACKGROUND: Perfluorocarbon liquids (PFCLs) are used as intraoperative tools to
      stabilize the retina during vitreoretinal surgeries. Their use would be much
      facilitated if PFCLs were colored and not transparent. We describe the
      development of a colored PFCL for vitreoretinal surgeries. METHODS:
      Perfluorohexyloctan (F6H8) was colored by adding a blue, biocompatible
      anthraquinone dye, and then mixed with perfluorodecalin (PFD) or perfluorooctane
      (PFO) at different volume percentages. The thus-obtained colored PFCLs were
      incubated with lens, lens capsule, vitreous body, and retina of enucleated
      porcine eyes for staining purpose and analyzed microscopically. To analyze
      possible interactions between colored PFCLs and silicone oil, colored PFCLs were
      exchanged to BSS and silicone oil respectively in enucleated pig eyes. RESULTS:
      By mixing different volume% of colored F6H8 with perfluorodecalin (PFD) or
      perfluorooctane (PFO), colored PFCLs of different density and staining intensity
      were obtained. Cornea, lens, lens capsule, vitreous, and retina showed no signs
      of staining after incubation with colored PFCLs for 10 min. Colored PFCLs were
      transparent despite intense coloring, thus allowing a clear visibility of the
      underlying tissue. Immediately after instillation of silicone oil, the colored
      PFCL bubble was well-defined, and colored PFCL was easily aspirated. After 5
      minutes reaction time, considerable diffusion of the dye from the PFCL bubble
      into the silicone oil was observed. CONCLUSIONS: The staining intensity can be
      varied according to the volume% of the colored F6H8 phase. Colored PFCL is
      clearly visible when installed in the vitreous cavity of a pig eye, and can
      easily be removed. It does not stain the intraocular tissues in pig eyes. Colored
      PFCL can be exchanged with silicone oil. But a time-dependent diffusion of the
      dye into the silicone oil was observed in pig eyes, indicating that the contact
      should be limited.

PMID- 22134714
TI  - Relationship between femtosecond laser parameters and quality of the corneal
      stromal bed surface.

PMID- 22134713
TI  - Plasma homocysteine, serum folic acid, serum vitamin B12, serum vitamin B6, MTHFR
      and risk of pseudoexfoliation glaucoma: a meta-analysis.
AB  - BACKGROUND: The aim of this meta-analysis is to explore the relationship between
      plasma total homocysteine (tHcy) levels, serum folic acid, vitamin B12 and
      vitamin B6 levels, methylenetetrahydrofolate reductase (MTHFR) C677T genotype and
      risk of pseudoexfoliation glaucoma (PEXG). METHODS: A systematic search of EMBASE
      and PubMed of relevant articles was carried out for all published articles. Main
      outcome measures included the calculation of plasma tHcy levels, serum folic
      acid, vitamin B12, and vitamin B6 levels mean difference and odds ratios (OR) of
      MTHFR C677T genotype between cases and controls. RESULTS: There were 14 studies
      for tHcy (485 cases and 456 controls), five studies for folic acid (188 cases and
      189 controls), six studies for vitamin B12 (199 cases and 225 controls), three
      studies for vitamin B6 (128 cases and 130 controls) and eight studies for MTHFR
      (479 cases and 661 controls). Overall, the mean plasma tHcy levels in cases was
      3.38 umol/l (95% confidence intervals (CI): 2.35-4.42) higher than in controls.
      Serum folic acids, but not vitamin B12 and vitamin B6 levels, was significantly
      lower in cases than in controls; the weighted mean differences with 95% CI were 
      1.50 umol/l (-2.53, -0.46), -36.29 umol/l (-81.27, 8.68) and -0.60 umol/l (-2.55,
      1.35) respectively. There was no evidence of association between the MTHFR C677T
      genotype and PEXG (OR = 1.28, 95% CI: 0.85, 1.93). CONCLUSIONS: PEXG is
      associated with elevated plasma tHcy and low serum folic acid levels, but not
      serum vitamin B12, vitamin B6 levels, and MTHFR C677T genotype.

PMID- 22134715
TI  - CD29 expressed on plasma cells is activated by divalent cations and soluble CD106
      contained in the bone marrow plasma: refractory activation is associated with
      enhanced proliferation and exit of clonal plasma cells to circulation in multiple
      myeloma patients.
AB  - Malignant plasma cells (PC) in human multiple myeloma (MM) are retained in the
      bone marrow (BM) microenvironment. Using HUTS21 monoclonal antibody that reacts
      with active CD29 integrin, we demonstrate that this active form is tightly
      regulated by divalent cations and soluble CD106 (sCD106) contained in the BM
      plasma. Moreover, we also show that in vivo expression of the active CD29 on PC
      was clearly diminished in a minority of MM cases (HUTS21(-) patients). HUTS21(-)
      cells were refractory to the addition of either normal allogeneic BM plasma or
      optimal concentrations of exogenous divalent cations and recombinant sCD106.
      Furthermore, a lower binding to fibronectin was detected in comparison with
      HUTS21(+) PC. On the other hand, although HUTS21(-) PC showed a reduced amount of
      total (active+inactive) CD29, western-blot assays demonstrated that these clonal
      PC contained the two species of CD29, with molecular masses of 110 and 130 kDa,
      which were expressed on normal or HUTS21(+) PC. Finally, we detected a clear
      association between the presence of HUTS21(-) PC in the BM and an increased
      percentage of circulating PC with a high proliferative index, emphasizing the
      essential role of CD29 in the pathogenesis and progression of this disease.

PMID- 22134716
TI  - Dual inhibition of Jak2 and STAT5 enhances killing of myeloproliferative
      neoplasia cells.

PMID- 22134717
TI  - Polymorphisms in the TLR6 gene associated with the inverse association between
      childhood acute lymphoblastic leukemia and atopic disease.
AB  - Little is known about the etiology of childhood acute lymphoblastic leukemia
      (ALL). The presence of atopic disease has been shown to protect against
      developing childhood ALL. The aim of this study was to examine whether single
      nucleotide polymorphisms (SNPs) in innate immunity genes previously associated
      with atopic disease, can elucidate the inverse association between childhood ALL
      and atopic disease. We studied 525 children, including 192 with childhood ALL,
      149 with atopic disease and 184 healthy control subjects. We compared genotype
      distributions of 29 SNPs in genes of TLR2, TLR4, TLR6, TLR9, TLR10 and CD14
      between the three groups and corrected for multiple testing. The genotype
      distributions of two SNPs in the TLR6 gene, rs5743798 and rs6531666, differed
      significantly between children with ALL, children with atopic disease and control
      subjects. Particularly in children with atopic eczema, risk alleles for atopic
      disease were observed more often than in control subjects, and less often in
      children with ALL than in control subjects. These findings support the immune
      surveillance hypothesis as an explanation for the protective association of
      atopic disease on childhood ALL. Further investigation is warranted to examine in
      more detail the role of innate immunity in the development of childhood ALL.

PMID- 22134718
TI  - Anticancer effect and feasibility study of hyperthermia treatment of pancreatic
      cancer using magnetic nanoparticles.
AB  - We investigated the effect and feasibility of hyperthermia treatment on
      subcutaneous pancreatic cancer in female Kunming mice, using a murine pancreatic
      cancer cell line (MPC-83) established by us and found in this study to originate
      from epithelial pancreatic acinus. Magnetic fluid (MF) with ferromagnetic
      particles of about 20 nm in size was used as a heating mediator. MF was injected
      into the subcutaneous nodules with subaxillary regions of mice 10 days after
      tumor transplantation; homogeneous distribution of magnetic nanoparticles in
      nodules was easily detected by X-ray 24 h later. Mice were allocated to four
      groups as follows: no treatment (control); MF injection alone; alternating
      magnetic field (AMF) irradiation alone; and MF injection and hyperthermia
      generated by applying AMF (300 kHz, 110 Gs). The two hyperthermia-treated
      subgroup tumors reached central temperatures of 47 and 51C, respectively, for 30
      min; while rectal temperature in both subgroups remained below 36C. Tumor growth
      was inhibited and survival significantly prolonged in the hyperthermia group
      compared with other groups (P<0.05). Tumor cells near the MF in the hyperthermia
      group apoptosed or necrosed immediately after hyperthermia. By day 14, there were
      no subcutaneous nodules; and residual magnetic nanoparticles were ingested by
      phagocytes. Nuclear proliferating cell nuclear antigen (PCNA) decreased in
      hyperthermia group tumor cells compared to the other groups; cytoplasmic heat
      shock protein 70 (HSP 70) was conspicuously higher immediately after hyperthermia
      (P<0.05). This technique had therapeutic potential and provided a new idea in the
      treatment of pancreatic cancer.

PMID- 22134719
TI  - Crystal structure of malonyl CoA-Acyl carrier protein transacylase from
      Xanthomanous oryzae pv. oryzae and its proposed binding with ACP.
AB  - Xanthomonas oryzae pv. oryzae (Xoo) is a plant bacterial pathogen that causes
      bacterial blight (BB) disease, resulting in serious production losses of rice.
      The crystal structure of malonyl CoA-acyl carrier protein transacylase (XoMCAT),
      encoded by the gene fabD (Xoo0880) from Xoo, was determined at 2.3 A resolution
      in complex with N-cyclohexyl-2-aminoethansulfonic acid. Malonyl CoA-acyl carrier
      protein transacylase transfers malonyl group from malonyl CoA to acyl carrier
      protein (ACP). The transacylation step is essential in fatty acid synthesis.
      Based on the rationale, XoMCAT has been considered as a target for antibacterial
      agents against BB. Protein-protein interaction between XoMCAT and ACP was also
      extensively investigated using computational docking, and the proposed model
      revealed that ACP bound to the cleft between two XoMCAT subdomains.

PMID- 22134720
TI  - Orosomucoid serum concentrations and fat depot-specific mRNA and protein
      expression in humans.
AB  - Obesity is associated with chronic low-grade inflammation, which contributes to
      systemic metabolic irregularities and obesity-linked metabolic disorders.
      Orosomucoid (ORM), an acute phase reactant protein, was shown to be produced in
      response to metabolic and inflammatory signals in the adipose tissue of obese
      mice, which protects them from severe inflammation and subsequent metabolic
      dysfunction. In this study, we examined whether there are site-specific
      differences between visceral and subcutaneous adipose tissue (VAT and SAT,
      respectively) ORM gene and protein expression from individuals with a wide range
      of obesity and the relationship between expressed and circulating ORM levels and
      measures of adiposity, insulin resistance, and pro- and anti-inflammatory markers
      and adipokines. The level of circulating ORM correlated positively with BMI, body
      fat mass, and serum leptin. It also correlated with fasting insulin, HOMA-IR
      values and C-reactive protein in men. There were no site-specific differences in
      ORM mRNA and protein expression between VAT and SAT, nor did we find a
      relationship between circulating ORM levels and its mRNA expression in either fat
      depot. We found that ORM mRNA expression correlated with mRNA expression of TNF
      alpha, IL-6, and adiponectin in VAT, and with TNF-alpha and adiponectin in SAT.
      These observations are the first description linking adipose tissue ORM and pro-
      and anti-inflammatory molecules in humans. The close links of ORM and measures of
      adiposity, insulin resistance, and adipose tissue inflammation in humans
      reinforce previous experimental data and warrant further studies to explore a
      possible role of ORM in the pathogenesis of obesity-associated metabolic
      derangements.

PMID- 22134721
TI  - Suppression of NS3 and MP is important for the stable inheritance of RNAi
      mediated rice stripe virus (RSV) resistance obtained by targeting the fully
      complementary RSV-CP gene.
AB  - Rice stripe virus (RSV) is a viral disease that seriously impacts rice production
      in East Asia, most notably in Korea, China, and Japan. Highly RSV-resistant
      transgenic japonica rice plants were generated using a dsRNAi construct designed
      to silence the entire sequence region of the RSV-CP gene. Transgenic rice plants
      were inoculated with a population of viruliferous insects, small brown
      planthoppers (SBPH), and their resistance was evaluated using ELISA and an
      infection rate assay. A correlation between the expression of the RSV-CP
      homologous small RNAs and the RSV resistance of the transgenic rice lines was
      discovered. These plants were also analyzed by comparing the expression pattern
      of invading viral genes, small RNA production and the stable transmission of the
      RSV resistance trait to the T3 generation. Furthermore, the agronomic trait was
      stably transmitted to the T4 generation of transgenic plants.

PMID- 22134722
TI  - Development of a simple and efficient system for excising selectable markers in
      Arabidopsis using a minimal promoter::Cre fusion construct.
AB  - The development of rapid and efficient strategies to generate selectable marker
      free transgenic plants could help increase the consumer acceptance of genetically
      modified (GM) plants. To produce marker-free transgenic plants without
      conditional treatment or the genetic crossing of offspring, we have developed a
      rapid and convenient DNA excision method mediated by the Cre/loxP recombination
      system under the control of a -46 minimal CaMV 35S promoter. The results of a
      transient expression assay showed that -46 minimal promoter::Cre recombinase (
      46::Cre) can cause the loxP-specific excision of a selectable marker, thereby
      connecting the 35S promoter and beta-glucuronidase (GUS) reporter gene. Analysis
      of stable transgenic Arabidopsis plants indicated a positive correlation between
      loxP-specific DNA excision and GUS expression. PCR and DNA gel-blot analysis
      further revealed that nine of the 10 tested T(1) transgenic lines carried both
      excised and nonexcised constructs in their genomes. In the subsequent T(2)
      generation plants, over 30% of the individuals for each line were marker-free
      plants harboring the excised construct only. These results demonstrate that the 
      46::Cre fusion construct can be efficiently and easily utilized for producing
      marker-free transgenic plants.

PMID- 22134724
TI  - West Nile Virus workshop: scientific considerations for tissue donors.
AB  - This report contains selected excerpts, presented as a summary, from a public
      workshop sponsored by the American Association of Tissue Banks (AATB) held to
      discuss West Nile Virus (WNV) and scientific considerations for tissue donors.
      The daylong workshop was held 9 July 2010 at the Ritz-Carlton Hotel at Tyson's
      Corner in McLean, Virginia, United States (U.S.). The workshop was designed to
      determine and discuss scientific information that is known, and what is not
      known, regarding WNV infection and transmission. The goal is to determine how to
      fill gaps in knowledge of WNV and tissue donation and transplantation by pursuing
      relevant scientific studies. This information should ultimately support decisions
      leading to appropriate tissue donor screening and testing considerations.
      Discussion topics were related to identifying these gaps and determining possible
      solutions. Workshop participants included subject-matter experts from the U.S.
      Food and Drug Administration, the Centers for Disease Control and Prevention,
      U.S. Department of Health and Human Services, Health Canada, the Public Health
      Agency of Canada, AATB-accredited tissue banks including reproductive tissue
      banks, accredited eye banks of the Eye Bank Association of America, testing
      laboratories, and infectious disease and organ transplantation professionals.
      After all presentations concluded, a panel addressed this question: "What are the
      scientific considerations for tissue donors and what research could be performed
      to address those considerations?" The slide presentations from the workshop are
      available at: http://www.aatb.org/2010-West-Nile-Virus-Workshop-Presentations.

PMID- 22134723
TI  - Leaf variegation in the rice zebra2 mutant is caused by photoperiodic
      accumulation of tetra-cis-lycopene and singlet oxygen.
AB  - In field conditions, the zebra2 (z2) mutant in rice (Oryza sativa) produces
      leaves with transverse pale-green/yellow stripes. It was recently reported that
      ZEBRA2 encodes carotenoid isomerase (CRTISO) and that low levels of lutein, an
      essential carotenoid for non-photochemical quenching, cause leaf variegation in
      z2 mutants. However, we found that the z2 mutant phenotype was completely
      suppressed by growth under continuous light (CL; permissive) conditions, with
      concentrations of chlorophyll, carotenoids and chloroplast proteins at normal
      levels in z2 mutants under CL. In addition, three types of reactive oxygen
      species (ROS; superoxide [O2-], hydrogen peroxide [H2O2], and singlet oxygen
      [1O2]) accumulated to high levels in z2 mutants grown under short-day conditions
      (SD; alternate 10-h light/14-h dark; restrictive), but do not accumulate under CL
      conditions. However, the levels of lutein and zeaxanthin in z2 leaves were much
      lower than normal in both permissive CL and restrictive SD growth conditions,
      indicating that deficiency of these two carotenoids is not responsible for the
      leaf variegation phenotype. We found that the CRTISO substrate tetra-Cis-lycopene
      accumulated during the dark periods under SD, but not under CL conditions. Its
      accumulation was also positively correlated with 1O2 levels generated during the
      light period, which consequently altered the expression of 1O2-responsive and
      cell death-related genes in the variegated z2 leaves. Taking these results
      together, we propose that the z2 leaf variegation can be largely attributed to
      photoperiodic accumulation of tetra-cis-lycopene and generation of excessive 1O2
      under natural day-night conditions.

PMID- 22134725
TI  - Spiro[pyrrolidine-2,3'-oxindole] derivatives synthesized by novel regionselective
      1,3-dipolar cycloadditions.
AB  - A series of spiro-oxindole derivatives was synthesized by novel regioselective
      1,3-dipolar cycloadditions of isatin, alpha-amino acids, and (E)-beta-aryl-nitro
      olefins. Regioisomers were produced in each reaction and the major products
      showed different regioselectivity compared to previously reported spiro-oxindole
      derivatives.

PMID- 22134726
TI  - Microfluidic approach for highly efficient synthesis of heparin-based
      bioconjugates for drug delivery.
AB  - This paper demonstrates the highly efficient synthesis of amphiphilic heparin
      folic acid-retinoic acid (HFR) bioconjugates with a high drug coupling ratio by a
      microfluidic approach. The microfluidic synthesis enabled the conjugation of 17
      molecules of retinoic acid to each heparin chain with 21 possible groups for
      attachment after reacting for several minutes. In contrast, about 11 molecules of
      the drug were covalently conjugated to one heparin chain after 4 days in the bulk
      reaction. The microfluidic based-HFR bioconjugates readily self-assembled in
      aqueous media to form uniform nanoparticles, while the product from the bulk
      reaction formed non-uniform nanoparticles with broad size distribution. The HFR
      nanoparticles with high drug content effectively delivered the drug to folate
      receptor-positive cancer cells with superior cellular uptake and selective
      cytotoxicity in vitro compared to HFR nanoparticles synthesized in bulk reaction.
      With the ability to achieve high drug content in heparin carrier within a short
      reaction time, the microfluidic technique offers new alternatives for the
      efficient synthesis of polymer-based conjugates for drug delivery.

PMID- 22134727
TI  - Phosphoproteomic studies of receptor tyrosine kinases: future perspectives.
AB  - In the last decade, large-scale mass spectrometry-based phosphoproteomic studies
      of receptor tyrosine kinases (RTKs) have generated a compendium of signalling
      networks that are activated downstream of these receptors. In this article, a
      brief summary of previous phosphoproteomic studies on epidermal growth factor
      receptor (EGFR) signalling will be presented together with a perspective on the
      importance for the field to keep pace with new advances in RTK biology. Using
      examples drawn primarily from studies on the EGFR, c-Met and Flt3 receptors,
      areas in RTK biology which will greatly benefit from the power of
      phosphoproteomics will be discussed, including (a) validating oncogenic RTK
      mutants identified in cancer genome sequencing efforts, (b) spatial RTK
      signalling networks and (c) understanding crosstalk and co-activation between
      members of the RTK superfamily.

PMID- 22134728
TI  - Therapeutical doses of temozolomide do not impair the function of dendritic cells
      and CD8+ T cells.
AB  - The median survival of patients with glioblastoma multiforme (GBM) remains poor.
      Innovative immunotherapies with dendritic cell (DC) vaccination might be combined
      with standard temozolomide (TMZ) treatment. Here, we evaluated the influence of
      TMZ on the phenotype and function of DCs and CD8+ T cells. DCs were generated
      from the peripheral blood of healthy volunteers (HVs) and GBM patients. DCs were
      analyzed by light microscopy and flow cytometry. Phagocytic activity was tested
      by FITC-dextran engulfment. Mixed lymphocyte peptide cultures were followed by
      enzyme-linked immunospot (ELISPOT) and flow cytometry assays. TMZ was added to DC
      and T cell cultures at concentrations up to 500 uM. Mature DCs were generated
      from HVs and GBM patients. Cells displayed a typical DC morphology and a mature
      DC phenotype. Expression of CD209 was even higher in DCs generated from patients
      under therapy than from HVs (75.2 vs. 51.1%). In contrast, CD40 (1.1 vs. 13.5%)
      and BDCA4 (26.5 vs. 52.9%) were lower expressed in GBM patients at time of
      diagnosis. Immature DCs showed high phagocytic activity. Addition of TMZ at
      concentrations up to 50 uM did neither impair the phenotype nor the function of
      DCs. In ELISPOT and flow cytometry assays, no impairment of CD8+ T cell responses
      to viral antigens could be observed. Taken together, TMZ does not impair the
      function of either DCs or the CD8+ T cells.

PMID- 22134729
TI  - Idiopathic thoracic spinal cord herniation: report of 10 patients and description
      of surgical approach.
AB  - STUDY DESIGN: Ten patients with idiopathic spinal cord herniation were treated
      surgically to reduce the herniation. In 9 patients, a sling was passed between
      the spinal cord and the anterior dural hiatus. The results were analyzed with
      respect to the neurological symptoms and imaging. OBJECTIVE: The study calls
      attention to an unusual condition with similar clinical presentation and
      characteristic imaging findings in the hope of improving early recognition and
      treatment. We present the outcome of treating patients with a safe technique that
      avoids the risks of primary dural closure and of cerebrospinal fluid leakage.
      SUMMARY OF BACKGROUND DATA: Over 100 patients with this disorder have been
      reported in the literature. Treatment in the past has included potentially
      hazardous attempts at primary dural closure of the dural hiatus, and the
      contraindicated step of biopsy, or even resection of herniated tissue. Various
      different surgical approaches have been used and the technique described by us
      has proved to be safe and effective. METHOD: : Nine patients underwent treatment
      by a similar sling technique; 1 patient was treated by a 2-stage more complex
      approach, which we have since abandoned. We begin with a laminectomy over the
      suspected level of cord herniation, followed by dural opening. The dentate
      ligaments are sectioned and the dural defect may have to be enlarged to safely
      disengage the herniated cord. The cord is elevated by the dentate ligaments and a
      bovine pericardial sling is passed under the cord, thereby occluding the dural
      hiatus. The epidural cavity and site of herniation may be filled with a variety
      of material, and an expansile duraplasty is performed. RESULTS: Sensory symptoms,
      weakness and spasticity, among the most common findings, improved in
      approximately one third of our patients. A long time interval between the
      appearance of symptoms, correct diagnosis, and appropriate treatment may reduce
      the chance of significant recovery. Severe pain may be a poor prognostic sign.
      The dural hiatus was located in the upper thoracic region in all of our patients.
      CONCLUSIONS: Idiopathic spinal cord herniation presents with symptoms and signs
      of spinal cord dysfunction and a very characteristic imaging appearance. The
      condition can be treated safely, with the expectation of neurological
      stabilization and some improvement. The technique described minimizes cord
      manipulation. Postoperative imaging often reflects the long-standing
      incarceration of the spinal cord.

PMID- 22134730
TI  - Lumbar spine fractures within a complete American cohort: epidemiology and risk
      factors among military service members.
AB  - STUDY DESIGN: Retrospective database review. OBJECTIVE: To describe the incidence
      of, and risk factors for, lumbar spine fractures within the population of the US
      military. SUMMARYOF BACKGROUND DATA: Fractures of the lumbar region are an
      important health concern; however, the epidemiology of this injury has not been
      extensively studied in the United States. METHODS: International Classification
      of Diseases, Clinical Modification, Ninth Revision codes for lumbar spine
      fractures were used in a search of the Defense Medical Epidemiology Database,
      identifying all individuals who sustained such injuries between 2001 and 2010.
      The database was also used to obtain the complete number of individuals serving
      in the Armed Forces over the same time period. Information regarding race, rank,
      branch of service, sex, and age was obtained for all individuals identified as
      having lumbar spine fractures as well as for the whole military population. The
      incidence of lumbar spine fractures was determined for the cohort. Unadjusted
      incidence rates were derived for risk factors and multivariate Poisson regression
      analysis, controlling for all other risks, was used to obtain adjusted incidence
      rate ratios and identify statistically significant risks for lumbar fractures.
      RESULTS: Between 2001 and 2010, the overall incidence of lumbar fractures was
      0.38 per 1000 person-years. Male sex, white race, enlisted ranks, service in the
      Army and Marines, and age were found to be significant predictors of lumbar spine
      fracture. Service in the Army demonstrated the highest rate of lumbar fractures
      (0.48 per 1000 person-years). CONCLUSIONS: This investigation is the first to
      document the incidence and postulate risk factors for lumbar spine fracture in an
      American population. In this study, males, whites, enlisted personnel, those
      serving in the Army and Marines, and individuals aged 20-24 or greater than 40
      were found to be at an increased risk of lumbar fracture.

PMID- 22134731
TI  - Should 25-hydroxyvitamin D and bone density using DXA be tested in adolescents
      with lumbar stress fractures of the pars interarticularis?
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To determine if 25-hydroxyvitamin D
      (25[OH]D) level measurement and bone mineral density (BMD) using dual-energy x
      ray absorptiometry (DXA) are indicated in children with a history of stress
      fracture of the pars interarticularis. SUMMARY OF BACKGROUND DATA: Healing rates
      of 4%-25% for bilateral and unilateral pars fractures, respectively, have
      previously been reported. Factors that may contribute to osteomalacia, rickets,
      and poor bone healing include low (25[OH]D) and low BMD. METHODS: Patients were
      seen at the Nebraska Spine Center between 2008 and 2010. Selection criteria
      included a diagnosis of pars fracture with DXA Z-score values (lumbar and hip)
      and pretreatment serum (25[OH]D) level measurement. Twenty-four patients were
      included. Vitamin D was defined as sufficient when >= 32 ng/mL, insufficient when
      20 to < 32 ng/mL, and deficient when < 20 ng/mL. BMD was interpreted from DXA Z
      scores using reference intervals defined in the literature. A Z-score <-2.0 was
      considered low for chronological age. RESULTS: The mean (+/- SD) vitamin D level
      was 29.9 ng/mL +/- 10.8 (range, 9-56 ng/mL). Values were <= 10 ng/mL in 1 patient
      (4%), 11-20 ng/mL in 4 patients (17%), 21-30 ng/mL in 8 patients (33%), 31-50
      ng/mL in 10 patients (42%), and > 50 ng/mL in 1 patient (4%). This correlated to
      3 (13%) patients with deficient vitamin D (<= 15 ng/mL), 12 (50%) patients with
      insufficient levels, and 9 (38%) with sufficient levels of vitamin D. The mean Z
      scores were 0.43 +/- 0.93 (lumbar, range, -1.3 to 2.8) and 1.0 +/- 1.11 (hip,
      range, -0.5 to 3.0). All scores were consistent with normal bony mineralization
      for age. CONCLUSIONS: On the basis of these data, we recommend routine vitamin D
      testing and do not recommend routine DXA in adolescents with lumbar stress
      fractures of the pars interarticularis.

PMID- 22134732
TI  - Comparison of the therapeutic effect of teriparatide with that of combined
      vertebroplasty with antiresorptive agents for the treatment of new-onset adjacent
      vertebral compression fracture after percutaneous vertebroplasty.
AB  - STUDY DESIGN: Comparing a prospective group of 32 patients, who underwent
      percutaneous vertebroplasty (PVP) and who were treated with teriparatide for at
      least 18 months after a new-onset adjacent vertebral compression fracture (VCF),
      and compared it with a retrospective group of 33 patients, who received
      antiresorptive agents combined with repeated PVPs for post-PVP new-onset adjacent
      VCFs. OBJECTIVE: This comparative study aimed to assess the immediate and mid
      term efficacy and safety of teriparatide for treating new adjacent VCFs after
      vertebroplasty. SUMMARY OF BACKGROUND DATA: Vertebroplasty may provoke fractures
      in adjacent, nonaugmented vertebrae. Subsequent VCFs can occur much sooner and
      more frequently after PVPs. Antiresorptive agents do not effectively prevent new
      onset VCFs or prompt pain relief. Treatment with teriparatide is effective and
      rapid in increasing spinal bone mineral density (BMD) and in decreasing vertebral
      fracture risk in patients with osteoporosis. METHODS: Relevant clinical data were
      compared between a prospective group of patients who received teriparatide and a
      retrospective group of patients who received antiresorptive agents and repeated
      PVPs for new-onset adjacent VCFs after PVP. RESULTS: Data in prospective group,
      including visual analogue scale scores and BMD were compared with those in a
      retrospective group. In group A, only 1 new-onset VCF occurred during the mean
      follow-up period of 22.56 months. In group B, 5 patients (6 vertebrae) developed
      new-onset VCFs after the second PVP, and 2 of these 5 patients had additional new
      VCFs after the third PVP. Teriparatide significantly reduced the risk of new VCFs
      after vertebroplasty (odds ratio=0.18; 95% confidence interval, 0.02-1.64). The
      increase of lumbar spine BMD was 26.32% after 18 months of treatment with
      teriparatide and 4.62% after 18 months of treatment with antiresorptive agents.
      In addition, at the 18-month follow-up, mean visual analogue scale scores had
      decreased from 8.03+/-1.97-1.37+/-0.52 in the teriparatide group and from 7.91+/
      1.95-4.23+/-1.21 in the antiresorptive group. CONCLUSIONS: For the treatment of
      new-onset adjacent VCF after PVPs, the therapeutic effects of teriparatide is
      better than that of the combined vertebroplasty and an antiresorptive agent in
      fracture prevention, BMD change, and sustained pain relief.

PMID- 22134733
TI  - Quantitative magnetic resonance imaging characteristics: evaluation of prognostic
      value in the dog as a translational model for spinal cord injury.
AB  - SUMMARY OF BACKGROUND DATA: The mechanisms of injury in spinal cord injury in
      dogs are similar to those in human patients and the dog is considered to be a
      valuable translational model for new treatment modalities. Studies regarding the
      quantitative characteristics of magnetic resonance imaging (MRI) findings in
      spinal cord injury in a uniform cohort of patients are lacking. OBJECTIVE AND
      STUDY DESIGN: The aim of this retrospective study was to evaluate the
      quantitative MRI signal characteristics of the spinal cord in T2-weighted (T2W)
      sequences, degree of spinal cord compression, and functional outcome in
      paraplegic dogs with thoracolumbar disk herniation proving the usefulness of
      imaging before treatment studies. METHODS: MR images of 63 paraplegic dogs with
      intact or absent deep pain perception due to thoracolumbar disk herniation
      examined between January 2005 and June 2009 were reviewed blinded to clinical
      information. The presence and degree of spinal cord compression, and the presence
      and length of an intramedullary hyperintensity on T2W images were correlated to
      clinical signs and outcome. RESULTS: A statistically significant correlation was
      seen between the neurological status before surgery and the presence and extent
      of the intramedullary hyperintensity adjacent to the disk herniation in T2W
      sequences. In dogs with a longer duration of clinical signs, the degree of spinal
      cord compression was statistically significantly higher. The extent of
      hyperintensity and the degree of spinal cord compression presented a positive
      correlation, whereas improvement in the neurological score for each grade was
      faster with no or a smaller size of T2W intramedullary hyperintensity.
      CONCLUSIONS: In conclusion, a direct correlation between neurological status and
      MRI signal intensity and extent was proven. Moreover, the presence and extent of
      T2W hyperintensity can help determine the prognosis before surgery and to decide,
      whether new therapeutical strategies in dogs as a translational model should be
      evaluated.

PMID- 22134734
TI  - Sacropelvic fixation with iliosacral screws: applications and results in adult
      spinal deformities.
AB  - STUDY DESIGN: Retrospective radiographic and clinical review. OBJECTIVE: To
      determine the feasibility of iliosacral screw fixation in adult spinal
      deformations. SUMMARY OF BACKGROUND DATA: Pelvic fixation is one of the most
      challenging instrumentation problems. The poor bone quality frequently found
      within the sacrum and the large lumbosacral loads with cantilever pullout forces
      across this region explain its frequent failure. METHODS: Fourteen adult patients
      undergoing pelvic fixation using iliosacral screws with a minimal follow-up of 24
      months were analyzed for radiographic outcomes. Radiographic data included the
      localization of the spinal deformity, the Cobb angle, T4-T12 thoracic kyphosis,
      L1-S1 lumbar lordosis, the T9 tilt, the pelvic parameters, and the POA.
      Mechanical and infectious complications were also noted. RESULTS: The lumbo
      pelvic correction was performed with a large reduction of the POA in every case.
      The frontal and sagittal corrections obtained with this procedure were considered
      as being effective. There were no mechanical complications due to failure of the
      instrumentation, loss of sacral fixation, or loss of lumbar lordosis at the time
      of the last follow-up. One patient experienced local infection on the left
      iliosacral screw without any residual functional sequel. DISCUSSION: Iliosacral
      screwing can offer a pelvic fixation reliable enough to allow restoration of 3
      dimensional trunk balance. This technique has a quite short learning curve and
      adequately permits frontal and sagittal corrections, increases stability, and
      decreases instrumentation-related complications. Our observations suggest that it
      is applicable to pelvic fixation in adult surgery.

PMID- 22134735
TI  - Treatment of facet cysts associated with neurogenic intermittent claudication
      with x-stop.
AB  - BACKGROUND: Facet degeneration often leads to the formation of synovial facet
      cysts. As facet cysts invade the spinal canal, they become a contributing factor
      to spinal stenosis. Previous studies have demonstrated successful treatment of
      neurogenic intermittent claudication (NIC), a major symptom of spinal stenosis,
      with an interspinous process device. PURPOSE: To compare clinical outcomes of
      patients with and without synovial facet cysts treated with an interspinous
      process device. STUDY DESIGN: Retrospective review of prospective data of
      consecutive patients undergoing the X-Stop procedure at an institution. OUTCOME
      MEASURES: Visual Analog Scale; Oswestry Disability Index; sitting, standing, and
      walking tolerances; and satisfaction survey. METHODS: Review of all patients from
      2006 to 2010 undergoing X-Stop procedure at an institution. Imaging studies were
      used to identify the presence and measure the size of the facet cysts in 285
      patients with a minimum of 6-month follow-up. Comparative clinical outcomes
      determined if X-Stop is a successful treatment option for patients with NIC in
      conjunction with synovial facet cysts (<3 mm, >=3 mm). RESULTS: Fifty-eight of
      285 patients (20.4%) were determined to have a synovial cyst as a contributing
      component of spinal stenosis. Twelve of 58 patients were noted to have a cyst >=3
      mm. The mean follow-up time for patients with and without a facet cyst was 21
      months (6-55+/-12 mo) and 22 months (6-61+/-12 mo), respectively. The age of the
      patient at the time of the operation with and without facet cysts was 73 (+/-10
      y). Patients without synovial cysts, with synovial cysts, and cysts >=3 mm had an
      average change in Oswestry Disability Index of 15.6, 15.8, and 16.2,
      respectively. Visual Analog Scale scores were 2.3, 1.8, and 2.3, respectively. In
      addition, on satisfaction surveys 72.4%, 82.0%, and 77.8% were either very or
      somewhat satisfied, respectively. Overall complications included 4 spinous
      process fracture, 4 hematomas, 1 wound infection, and 1 implant migration.
      CONCLUSIONS: No statistical difference was noted in any of the outcome measures
      among patients with small facet cysts, large facet cysts, or without facet cysts
      when treated with an interspinous process device. We can thus conclude that X
      Stop is an appropriate treatment consideration for NIC with or without the
      presence of synovial facet cysts.

PMID- 22134736
TI  - Comparison between subcutaneous closed-suction drainage and conventional closed
      suction drainage in adolescent idiopathic scoliosis patients undergoing posterior
      instrumented spinal fusion: a randomized control trial.
AB  - STUDY DESIGN: Prospective, randomized controlled clinical study. OBJECTIVE: To
      evaluate the efficacy of subcutaneous closed-suction drainage in reducing blood
      loss as compared with conventional closed-suction drainage in adolescent
      idiopathic scoliosis cases undergoing posterior instrumented spinal fusion.
      BACKGROUND: Subcutaneous closed-suction drainage is reported to be a reasonable
      alternative to intra-articular indwelling closed-suction drainage and to that of
      no usage of any drainage system in knee arthroplasty. However, little is reported
      about the use of subcutaneous closed-suction drainage in adolescents idiopathic
      scoliosis patients undergoing posterior instrumented spinal fusion. METHODS: A
      total of 105 adolescent idiopathic scoliosis patients undergoing posterior
      instrumented spinal fusion were randomized into 2 groups of either a subcutaneous
      drainage or a conventional closed-wound suction drainage system. These 2 groups
      were compared for demographic distribution, blood loss (hemoglobin/hematocrit
      changes, transfusion requirements), and incidence of wound problems (requirements
      for dressing reinforcement, oozing, subcutaneous hematoma, ecchymosis,
      infection). RESULTS: Mean drainage volume was less (P=0.000) in the subcutaneous
      closed-wound suction drainage group compared with the conventional closed-wound
      suction drainage group (42 vs. 631 mL). The groups were statistically similar in
      terms of hemoglobin and hematocrit values obtained on the third postoperative day
      (10.60 vs. 9.52 g/dL, P=0.110; 30.85% vs. 27.82%, P=0.226), on discharge (10.90
      vs. 9.75 g/dL, P=0.114; 31.10% vs. 28.13%, P=0.147), transfusion requirements
      (31.2% vs. 45.6%, P=0.133), and incidence of wound problems. However, the core
      temperature values were higher in subcutaneous closed-wound suction drainage
      group compared with the conventional closed-wound suction drainage group
      (P=0.001), and the duration of fever was longer in the former compared with the
      latter (P=0.008). CONCLUSIONS: The data suggest that subcutaneous closed-suction
      drainage offers a reasonable alternative to closed-wound suction drainage in
      adolescents idiopathic scoliosis patients undergoing posterior instrumented
      spinal fusion.

PMID- 22134737
TI  - Evaluating the performance of volunteers in mapping invasive plants in public
      conservation lands.
AB  - Citizen science programs are touted as useful tools for engaging the public in
      science and for collecting important data for scientists and resource managers.
      To accomplish the latter, it must be shown that data collected by volunteers is
      sufficiently accurate and reliable. We engaged 119 volunteers over three years to
      map and estimate abundance of invasive plants in New York and New Jersey
      parklands. We tested their accuracy via collected pressed samples and by
      subsampling their transect points. We also compared the performances of
      volunteers and botanical experts. Our results support the notion that volunteer
      participation can enhance the data generated by scientists alone. We found that
      the quality of data collected might be affected by the environment in which the
      data are collected. We suggest that giving consideration to how people learn can
      not only help to achieve educational goals but can also help to produce more data
      to be used in scientific study.

PMID- 22134738
TI  - GIS and the analytic hierarchy process for regional landfill site selection in
      transitional countries: a case study from Serbia.
AB  - The Serbian National Waste Management Strategy for the Period 2010-2019,
      harmonized with the European Union Directives, mandates new and very strict
      requirements for landfill sites. To enable analysis of a number of required
      qualitative and quantitative factors for landfill site selection, the traditional
      method of site selection must be replaced with a new approach. The combination of
      GIS and the Analytic Hierarchy Process (AHP) was selected to solve this complex
      problem. The Srem region in northern Serbia, being one of the most
      environmentally sensitive areas, was chosen as a case study. Seventeen factors
      selected as criteria/sub-criteria were recognized as most important, divided into
      geo-natural, environmental, social and techno-economic factors, and were
      evaluated by experts from different fields using an AHP extension in Arc GIS.
      Weighted spatial layers were combined into a landfill suitability map which was
      then overlapped with four restriction maps, resulting in a final suitability map.
      According to the results, 82.65% of the territory of Srem is unsuitable for
      regional landfill siting. The most suitable areas cover 9.14%, suitable areas
      5.24%, while areas with low and very low suitability cover 2.21 and 0.76% of the
      territory, respectively. Based on these findings, five sites close to two large
      urban agglomerations were suggested as possible locations for a regional landfill
      site in Srem. However, the final decision will require further field
      investigation, a public acceptance survey, and consideration of ownership status
      and price of the land.

PMID- 22134739
TI  - Graphene substrate-mediated catalytic performance enhancement of Ru
      nanoparticles: a first-principles study.
AB  - The structural, energetic and magnetic properties of Ru nanoparticles deposited
      on pristine and defective graphene have been thoroughly studied by first
      principles based calculations. The calculated binding energy of a Ru(13)
      nanoparticle on a single vacancy graphene is as high as -7.41 eV, owing to the
      hybridization between the dsp states of the Ru particles with the sp(2) dangling
      bonds at the defect sites. Doping the defective graphene with boron would further
      increase the binding energy to -7.52 eV. The strong interaction results in the
      averaged d-band center of the deposited Ru nanoparticle being upshifted toward
      the Fermi level from -1.41 eV to -1.10 eV. Further study reveals that the
      performance of the nanocomposites against hydrogen, oxygen and carbon monoxide
      adsorption is correlated to the shift of the d-band center of the nanoparticle.
      Thus, Ru nanoparticles deposited on defective graphene are expected to exhibit
      both high stability against sintering and superior catalytic performance in
      hydrogenation, oxygen reduction reaction and hydrogen evolution reaction.

PMID- 22134740
TI  - Gene therapy for SCID-X1: focus on clinical data.

PMID- 22134743
TI  - Interfering with tumor pathways that augment viral oncolysis.

PMID- 22134744
TI  - lncRNAs: finding the forest among the trees?

PMID- 22134745
TI  - Gene transfer using HACs: a key step closer to ex vivo gene therapy using
      autologous gene-corrected cells to treat muscular dystrophy.

PMID- 22134746
TI  - New polynuclear U(IV)-U(V) complexes from U(IV) mediated uranyl(V)
      disproportionation.
AB  - U(IV) promotes the disproportionation of otherwise stable uranyl(V) Schiff base
      complexes affording U(IV)-U(V) oxo clusters with new geometries and the first
      example of a U(IV)...UO(2)(+) cation-cation interaction.

PMID- 22134747
TI  - Three self-penetrated, interlocked, and polycatenated supramolecular isomers via
      one-pot synthesis and crystallization.
AB  - Three supramolecular isomers, {[Cd(2)(TPOM)(hfipbb)(2)].x/y/zsolvent}(n) (1-3),
      have been synthesized and characterized by one-pot reaction. Even though the
      compositions of 1-3 are the same, they generate different structures. Reactions
      over various time periods were found to influence the formation of supramolecular
      isomers, and there is little influence on this system under other conditions.

PMID- 22134748
TI  - Outcome of operation in patients with adrenocortical cancer invading the inferior
      vena cava--a European Society of Endocrine Surgeons (ESES) survey.
AB  - BACKGROUND: Most patients with adrenocortical cancer (ACC) continue to present
      with advanced disease. Invasion into the inferior vena cava (IVC) defines stage
      III disease and the management of such patients raises additional difficulties.
      METHOD: A multicentre survey was organized by emailing a standardized proforma to
      members of the European Society of Endocrine Surgery (ESES). Anonymised
      retrospective clinical data were collected. RESULTS: Replies were received from
      18 centres in nine countries. ACC with IVC invasion was encountered in 38
      patients (18F:20M, age 15-84 years, median 54 years). There were 16
      nonfunctioning tumours and 22 functioning tumours predominantly right-sided
      (26R:12L) and measuring 18-255 mm (median 115 mm). Fourteen patients had
      metastatic disease at presentation. Tumour thrombus extended in the prehepatic
      IVC (n = 21), subdiaphragmatic IVC (n = 6) or into the SVC/right atrium (n = 3).
      Open adrenalectomy was associated with resection of surrounding viscera in 24
      patients (nephrectomy n = 16, liver resection n = 14, splenectomy n = 3, Whipple
      procedure n = 2). IVC was controlled locally (n = 27), at suprahepatic levels (n
      = 6) or necessitated cardiac bypass (n = 5). Complete resection (R0, n = 20) was
      achieved in the majority of patients, with a minority having microscopic
      persistent disease (R1, n = 7) or macroscopic residual disease (R2, n = 4).
      Perioperative 30-day mortality was 13% (n = 5). Postoperative Mitotane was used
      in 23 patients and chemotherapy in eight patients. Twenty-five patients died 2-61
      months after their operation (median 5 months). Currently, 13 patients are alive
      at 2-58 months (median 16 months) with known metastatic disease (n = 7) or with
      no signs of distant disease (n = 6). CONCLUSION: This dataset is limited by the
      lack of a denominator as it remains unknown how many other patients with ACC
      presenting with IVC invasion did not undergo surgery. The relatively low
      perioperative mortality and the long disease-free survival achieved by some
      patients should encourage surgeons with adequate experience to offer surgical
      treatment to patients presenting with advanced adrenocortical cancers.

PMID- 22134749
TI  - The impact of abdominal shape index of patients on laparoscopy-assisted distal
      gastrectomy for early gastric cancer.
AB  - PURPOSE: The aim of this study was to explore the effects of the abdominal shape
      index on gastric cancer patients' short-term surgical outcomes of laparoscopy
      assisted distal gastrectomy (LADG) in both genders. METHODS: This retrospective
      study included 231 consecutive patients with early gastric cancer who underwent
      LADG with Billroth I anastomosis between 1998 and 2009. The abdominal shape index
      of patients was calculated using preoperative abdominal computed tomography scans
      and the Fat Scan software program. RESULTS: In male patients, the duration of
      surgery was longer in patients with a body mass index >=25 kg/m(2) (P = 0.016),
      with the anterior to posterior diameter >=200 mm (P < 0.0001), with the
      transverse diameter (TD) >=300 mm (P = 0.030), with the waist >=85 cm (P =
      0.039), and with the visceral fat area (VFA) >=100 cm(2) (P = 0.029). The
      intraoperative blood loss was higher in the large TD group (P = 0.049), in the
      high waist group (P = 0.006), and in the large VFA group (P = 0.007). In female
      patients, the correlations between these surgical outcomes and this abdominal
      shape index were not found. No significant relationships between each body shape
      index and the number of lymph nodes retrieved were found in either gender.
      Postoperative complications were not associated with the fat volume and abdominal
      shape index. CONCLUSIONS: Accumulation of fat did not affect short-term surgical
      outcomes except for the duration of surgery and intraoperative blood loss in male
      patients.

PMID- 22134750
TI  - Response to traditional disease-modifying anti-rheumatic drugs in indigent South
      Africans with early rheumatoid arthritis.
AB  - The clinical response to traditional disease-modifying anti-rheumatic drugs
      (DMARDs) in indigent South Africans with early rheumatoid arthritis was
      investigated. A cohort of patients with early (<=2 years) RA who were DMARD-naive
      at inception were prospectively assessed for response to DMARDs using the
      Simplified Disease Activity Index (SDAI) over a 12-month period. Patients with
      low disease activity (LDA) at 12 months were compared to those with moderate and
      high disease activity with respect to demographic, clinical, autoantibody and
      radiographic features. The 171 patients (140 females) had a mean (SD) age of 47.1
      (12.4) years, symptom duration of 11.7 (7.1) months and baseline SDAI of 39.4
      (16.2). There was a significant overall improvement in the SDAI and its
      components in the 134 (78.4%) patients who completed the 12 months visit, but
      only 28.4% of them achieved LDA. The majority of patients (91%) were treated with
      methotrexate as monotherapy or in combination with chloroquine and/or
      sulphasalazine. Baseline features that independently predicted a LDA state at 12
      months were lower Health Assessment Questionnaire Disability Index (p = 0.023)
      and a higher haemoglobin level (p = 0.048). Receiver operating characteristic
      curve analysis showed that the 6-month SDAI was better than the baseline SDAI in
      predicting the 12-month SDAI (area under the curve of 0.69 vs. 0.52,
      respectively, p = 0.008). In conclusion, less than a third of the patients
      achieved a low disease activity at 12 months on traditional DMARDs. Patients who
      have an inadequate response to traditional DMARDs at 6 months are unlikely to
      show further improvement on traditional DMARDs at 12 months. These findings
      underscore the need for better disease control by an aggressive tight control
      strategy, including intense patient education and biologic therapy.

PMID- 22134751
TI  - Sentinel node navigation surgery attenuates the functional disorders in early
      gastric cancer.
AB  - The purpose of this study was to evaluate the merits of the sentinel node (SN)
      navigated reduced gastrectomy (SNRG) procedure. The subjects (sT1N0) were divided
      into the SNRG group (n=34) and the GL group, that consisted of patients which
      underwent gastrectomy according to the Japanese Gastric Cancer Association
      guidelines (n=33). We compared the area of the resected stomach and evaluated
      their body weight changes, and the results of a questionnaire survey about
      postoperative symptoms, and nutritional effects by blood tests administered at
      postoperative months (POM) 3, 6 and 12. The median area of the resected stomach
      was 104 cm2 in the SNRG group vs. 192 cm2 in the GL group. The body weight loss
      ratio was -5.9+/-5.8 vs. -9.3+/-4.1% at POM 3, and the henoglobin (g/dl) change
      rate was -1.1+/-7.9 vs. -6.4+/-6.5% at POM 12 in the SNRG and GL groups,
      respectively. There were no significant differences regarding the passage of
      food, reflux, the incidence of dumping syndrome, digestive and excretory
      function, or general condition and the satisfaction levels of the patients. In
      conclusion, SNRG has some advantages over GL in terms of postoperative disorders
      for at least one year after surgery, and is the recommended choice of a surgical
      procedure for early gastric cancer.

PMID- 22134753
TI  - Toward active-matrix lab-on-a-chip: programmable electrofluidic control enabled
      by arrayed oxide thin film transistors.
AB  - Agile micro- and nano-fluidic control is critical to numerous life science and
      chemical science synthesis as well as kinetic and thermodynamic studies. To this
      end, we have demonstrated the use of thin film transistor arrays as an active
      matrix addressing method to control an electrofluidic array. Because the active
      matrix method minimizes the number of control lines necessary (m + n lines for
      the m*n element array), the active matrix addressing method integrated with an
      electrofluidic platform can be a significant breakthrough for complex
      electrofluidic arrays (increased size or resolution) with enhanced function,
      agility and programmability. An amorphous indium gallium zinc oxide (a-IGZO)
      semiconductor active layer is used because of its high mobility of 1-15 cm(2) V(
      1) s(-1), low-temperature processing and transparency for potential spectroscopy
      and imaging. Several electrofluidic functionalities are demonstrated using a
      simple 2 * 5 electrode array connected to a 2 * 5 IGZO thin film transistor array
      with the semiconductor channel width of 50 MUm and mobility of 6.3 cm(2) V(-1) s(
      1). Additionally, using the TFT device characteristics, active matrix addressing
      schemes are discussed as the geometry of the electrode array can be tailored to
      act as a storage capacitor element. Finally, requisite material and device
      parameters are discussed in context with a VGA scale active matrix addressed
      electrofluidic platform.

PMID- 22134752
TI  - Associations of polymorphisms of folate cycle enzymes and risk of breast cancer
      in a Brazilian population are age dependent.
AB  - Polymorphisms in genes involved in folate metabolism have been shown to be
      implicated in breast cancer risk but with contradictory results. In this case
      control study, we investigated the association between MTHFR C677T and A1298C,
      TYMS 5'-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A)
      and breast cancer risk in a northeastern Brazilian population. The study included
      183 women diagnosed with breast cancer and 183 controls volunteers without any
      history of cancer. Also a significant number of healthy individuals were included
      for allelic frequency in the population studied. Risk of breast cancer was
      estimated by conditional logistic regression. An association with risk was found
      for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P =
      0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele
      (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50
      years old), different distributions were observed for breast cancer risk. For
      women <=50 years, the risk observed in the presence of the polymorphic allele MTR
      2756 (AG/GG) in the general analysis was, restricted to this age group (P =
      0.0118). Conversely, for women over 50, the risk of breast cancer development was
      statistically associated with the MTHFR 677CT genotype, but especially
      significant was risk associated with the presence of the polymorphic allele of
      cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A
      polymorphism allele (P = 0.0021), was restrict to this age group. These data
      indicate that the cutoff age used (50 years old) was appropriate, since it was
      able to discriminate risk in each age group in the population studied and also to
      point to the importance of age in the analyses of cancer-associated
      polymorphisms.

PMID- 22134754
TI  - Differential effects of PXD101 (belinostat) on androgen-dependent and androgen
      independent prostate cancer models.
AB  - Histone deacetylase inhibitors (HDACi) are promising epigenetic cancer
      chemotherapeutics rapidly approaching clinical use. In this study, we tested
      using in vitro and in vivo models the differential biological effects of a novel
      HDAC inhibitor [belinostat (PXD101)], in a wide panel of androgen-sensitive and
      androgen-independent tumor cells. Belinostat significantly increased acetylation
      of histones H3 and H4. Belinostat potently inhibited the growth of prostate
      cancer cell lines (IC50 range from 0.5 to 2.5 uM) with cytotoxic activity
      preferentially against tumor cells. This agent induced G2/M arrest and increased
      significantly the percentage of apoptosis mainly in androgen-sensitive tumor
      cells confirming its growth-inhibitory effects. The cell death mechanisms were
      studied in three different prostate cancer cell lines with different androgen
      dependence and expression of androgen receptor; LAPC-4 and 22rv1 (androgen
      dependent and expressing androgen receptor) and PC3 (androgen-independent not
      expressing androgen receptor). Belinostat induced the expression of p21 and p27,
      acetylation of p53 and G2/M arrest associated with Bcl2 and Bcl-Xl downmodulation
      and significant reduction of survivin, IAPs and Akt/pAkt and increased caspase-8
      and -9 expression/activity. Belinostat effectiveness was dependent on the
      androgen receptor (AR), since the stable transfection of AR greatly increased the
      efficacy of this HDAC inhibitor. These observations were correlated using in vivo
      models. We demonstrated that belinostat preferentially resulted in antitumor
      effect in androgen-dependent tumor cells expressing AR. Our findings provide
      evidence that belinostat may be a promising anticancer drug for prostate cancer
      expressing AR, supporting its clinical role in prostate cancer.

PMID- 22134755
TI  - Pseudo-occlusion of the extracranial carotid artery caused by intracranial
      carotid artery stenosis.

PMID- 22134756
TI  - Cell biology in India: the future needs an international perspective.

PMID- 22134757
TI  - Heeding a mentor's advice: a lesson in persistence.

PMID- 22134758
TI  - Phosphatidylserine promotes polar Cdc42 localization.
AB  - The establishment and maintenance of cell polarity requires targeted recruitment
      of polarity regulators to the plasma membrane. Phosphatidylserine is now shown to
      have a key role in polarization of yeast cells and the localization of the
      central polarity regulator Cdc42.

PMID- 22134759
TI  - Pulling together and pulling apart: collective cargo movement in eukaryotic
      cells.
AB  - To establish and maintain their internal organization, living cells must move
      molecules to their correct locations. Long-range intracellular movements are
      often driven by motor molecules moving along microtubules, similarly to trucks
      driving along a highway. Recent work demonstrates that some randomly dispersed
      cargos can generate actin filaments that form a connected network whose
      contraction drives collective cargo movement.

PMID- 22134767
TI  - Atypical teratoid/rhabdoid tumors: the need for more active therapeutic measures
      in younger patients.
AB  - Despite active and aggressive therapeutic measures, atypical teratoid/rhabdoid
      tumors (AT/RTs) are without doubt one of the most malignant brain tumors that
      occur during childhood. These tumors are more prevalent in children less than 3
      years of age, and the prognosis is worse in these young children. Medical records
      of 14 patients diagnosed at our institution were reviewed. Patients diagnosed
      with AT/RT at our institution between 1997 and 2009 were identified. Clinical
      data for those patients with pathologic confirmation of AT/RTs were reviewed
      regarding surgery, adjuvant treatment, and survival. A total of 14 patients were
      identified. One patient who died 3 days after initial surgery was excluded, and
      13 patients were recruited. Of the 13 patients, 7 were less than 1 year of age,
      and only 2 were over 3 years of age. Nine patients showed dissemination at
      diagnosis. Four patients were treated with radiation therapy (RTx), and 2 of
      these were less than 3 years of age. Ten patients had chemotherapy (CTx), and 3
      of these underwent high dose chemotherapy and autologous peripheral blood stem
      cell transplantation. The median progression-free survival (PFS) was 4 months,
      and the median overall survival (OS) was 9 months. Univariable analysis revealed
      age more than 1 year, CTx, and RTx to be significant factors for better PFS and
      OS. None of the variables were significant in multivariable analysis. Young
      patients with AT/RT have a bad prognosis. An aggressive therapeutic strategy
      needs to be profiled for this age group.

PMID- 22134768
TI  - Koetjapic acid, a natural triterpenoid, induces apoptosis in colon cancer cells.
AB  - Deregulated cell signaling pathways result in cancer development. More than one
      signal transduction pathway is involved in colorectal cancer pathogenesis and
      progression. Koetjapic acid (KA) is a naturally occurring seco-A-ring oleanene
      triterpene isolated from the Sandoricum koetjape stem bark. We report the
      cellular and molecular mechanisms of anticancer activity of KA towards human
      colorectal cancer. The results showed that KA induces apoptosis in HCT 116
      colorectal carcinoma cells by inducing the activation of extrinsic and intrinsic
      caspases. We confirmed that KA-induced apoptosis was mediated by DNA
      fragmentation, nuclear condensation and disruption in the mitochondrial membrane
      potential. Further studies on the effect of KA on cancer pathways show that the
      compound causes down-regulation of Wnt, HIF-1alpha, MAP/ERK/JNK and Myc/Max
      signaling pathways and up-regulates the NF-kappaB signaling pathway. The result
      of this study highlights the anticancer potential of KA against colorectal
      cancer.

PMID- 22134769
TI  - Discotic hexa-peri-hexabenzocoronenes with strong dipole: synthesis, self
      assembly and dynamic studies.
AB  - Strong dipole moments have been built into two hexa-peri-hexabenzocoronene (HBC)
      derivatives (1 and 2) originating from the push-pull structure of the molecules
      with one electron-donating and one electron-withdrawing substituent. The
      influence of dipole moment on the self-assembly of HBCs in solution and in bulk
      has been investigated.

PMID- 22134770
TI  - Post hoc immunostaining of GABAergic neuronal subtypes following in vivo two
      photon calcium imaging in mouse neocortex.
AB  - GABAergic neurons in the neocortex are diverse with regard to morphology,
      physiology, and axonal targeting pattern, indicating functional specializations
      within the cortical microcircuitry. Little information is available, however,
      about functional properties of distinct subtypes of GABAergic neurons in the
      intact brain. Here, we combined in vivo two-photon calcium imaging in
      supragranular layers of the mouse neocortex with post hoc immunohistochemistry
      against the three calcium-binding proteins parvalbumin, calretinin, and calbindin
      in order to assign subtype marker profiles to neuronal activity. Following
      coronal sectioning of fixed brains, we matched cells in corresponding volumes of
      image stacks acquired in vivo and in fixed brain slices. In GAD67-GFP mice, more
      than 95% of the GABAergic cells could be unambiguously matched, even in large
      volumes comprising more than a thousand interneurons. Triple immunostaining
      revealed a depth-dependent distribution of interneuron subtypes with increasing
      abundance of PV-positive neurons with depth. Most importantly, the triple
      labeling approach was compatible with previous in vivo calcium imaging following
      bulk loading of Oregon Green 488 BAPTA-1, which allowed us to classify
      spontaneous calcium transients recorded in vivo according to the neurochemically
      defined GABAergic subtypes. Moreover, we demonstrate that post hoc immunostaining
      can also be applied to wild-type mice expressing the genetically encoded calcium
      indicator Yellow Cameleon 3.60 in cortical neurons. Our approach is a general and
      flexible method to distinguish GABAergic subtypes in cell populations previously
      imaged in the living animal. It should thus facilitate dissecting the functional
      roles of these subtypes in neural circuitry.

PMID- 22134771
TI  - Participation of calbindin-D28K in nociception: results from calbindin-D28K
      knockout mice.
AB  - Since calbindin-D(28K) (CB-D(28K))-positive neurons have been related to
      nociceptive sensory processing, we have hypothesized that altered CB-D(28K)
      expression could alter nociceptive transmission. We have used +/+ and -/-
      knockout (KO) mice for CB-D(28k) in different behavioral models of pain and
      sensory responses at the caudalis subdivision of the trigeminal spinal nucleus in
      order to understand how this protein may participate in nociception. Behavioral
      responses to formalin injection in the hind paw or at the whisker pad or in the
      hind paw glutamate or i.p. acetic acid tests showed an increase of the pain
      threshold in CB-D(28k) -/- mice. KO mice showed a diminution of the inhibitory
      activity at Sp5C nucleus and a marked reduction of GABA content. Sp5C neurons
      from CB-D(28k) -/- mice did not change their spontaneous activity or tactile
      response after formalin injection in the whisker pad. In contrast, Sp5C neurons
      increased their spontaneous firing rate and tactile response after formalin
      injection in their receptive field in CB-D(28k) +/+ mice. The results of this
      study demonstrate the active role played by CB-D(28k) in nociceptive sensory
      transmission. The lack of this calcium binding protein, associated to deficient
      GABAergic neurotransmission, translates into dysfunction of sensory processing of
      nociceptive stimuli.

PMID- 22134772
TI  - Modulatory effects of Thymbra spicata L. different extracts against the mercury
      induced genotoxicity in human lymphocytes in vitro.
AB  - Mercury, a xenobiotic metal, is a highly deleterious environmental pollutant.
      Moreover, in any form mercury is reported to be toxic. On the other hand, Thymbra
      spicata L., a member of the Lamiaceae family, has long been investigated
      popularly of biological roles; mainly antimicrobial and antioxidant activities.
      However, there are very scarce data on the cytogenetic effects of thyme species.
      The purpose of this study was to investigate the genetic safety of  different
      extracts from T. spicata (water extract, methanol extract, and ethanol extract)
      and the effects of T. spicata on mercury (as HgCl(2)) induced genotoxicity.
      Sister chromatid exchange (SCE) and micronucleus (MN) assays were performed to
      assess DNA damages in cultured human lymphocytes (n = 5). Our results clearly
      revealed that, the SCE and MN rates induced by HgCl(2) were alleviated by the
      presence of T. spicata. As conclusion, this study demonstrated for the first time
      that the T. spicata provided increased resistance of DNA against HgCl(2) induced
      genetic damage in human lymphocytes. Based on the results of this study, it may
      be concluded that the T. spicata is a nontoxic material that could be used as a
      suppressor of heavy metal-induced genotoxicity.

PMID- 22134773
TI  - In vitro expansion of human glioblastoma cells at non-physiological oxygen
      tension irreversibly alters subsequent in vivo aggressiveness and AC133
      expression.
AB  - Among markers of glioblastoma initiating cells, AC133 has been shown to be
      associated with glioblastoma resistance and malignancy. Recently, it was
      demonstrated that increasing oxygen tension (pO2) down-regulated AC133 expression
      in glioblastoma cells in vitro. In order to better understand extrinsic factor
      regulation of AC133, this work aimed to investigate the relationship between cell
      culture pO2, AC133 expression, and tumor development and phenotype. Using
      treatments with CoCl2 and HIF-1alpha shRNA knockdowns on non-sorted human primary
      glioblastoma cells cultured at low (3%) versus high (21%) oxygen tension, we
      established a responsibility for low pO2 in the maintenance of high levels of
      AC133 expression, with a major but non-exclusive role for HIF-1alpha. We also
      demonstrated that human glioblastoma cells previously cultured under high oxygen
      tension can lose part of their aggressiveness when orthotopically engrafted in
      SCID mice or lead to tumors with distinct phenotypes and no re-expression of
      AC133. These observations showed that the specific pO2 microenvironment
      irreversibly impacts glioblastoma cell phenotypes, highlighting the pertinence of
      culture conditions when extrapolating data from xenogenic models to human cells
      in their source environment. They also raised AC133 as a marker of non-exposure
      to oxygenated areas rather than a marker of aggressiveness or low pO2 niches.

PMID- 22134774
TI  - Suitability of initial antibiotic therapy for the treatment of bloodstream
      infections and the potential role of antibiotic management teams in improving it.
AB  - Hospital antibiotic management teams (AMTs) have been recommended, but, in
      France, their concrete implementation remains scarce and their effectiveness
      largely unevaluated. The objective of this investigation was to evaluate the
      appropriateness of antibiotic therapy (AT) for bloodstream infections (BSIs) at a
      950-bed university teaching hospital, and assess the role of an AMT in improving
      it. A prospective analysis of all significant BSIs occurring outside of the
      intensive care unit (ICU) during an 18-month period was carried out. AT was
      deemed effective if at least one prescribed antibiotic was effective in vitro,
      and appropriate if it was consistent with local recommendations. Out of 574 BSIs,
      512 were evaluated: 231 community-acquired, 206 nosocomial, and 75 healthcare
      associated. For 219 (42.8%) BSIs, the AT initiated prior to AMT intervention
      proved to be effective and appropriate, inappropriate but effective in 136
      (26.5%), and ineffective or absent in 157 (30.7%). In the multivariate analysis,
      hospital-acquired and other healthcare-associated BSIs, as well as catheter-borne
      (CB) infections, were associated with inappropriate or absent AT. A
      recommendation from the AMT was given and followed in 233 (94%) out of 249 BSIs
      requiring intervention. Initially, two-thirds of BSIs outside the ICU did not
      receive appropriate AT. Healthcare-associated BSIs should, therefore, be the
      priority target of AMTs.

PMID- 22134775
TI  - Canalis sinuosus: a rare anatomical variation.
AB  - The infraorbital canal issues a small branch on its lateral face close to its
      midpoint to allow passage of the anterior superior alveolar nerve. This small
      canal, sometimes called the canalis sinuosus, runs forward and downward to the
      inferior wall of the orbit, lateral to the infraorbital canal and medially bent
      to the anterior wall of the maxillary sinus, passing below the infraorbital
      foramen. Anatomical variations in the maxilla are rarely described in the
      literature and, in most cases, are related to the nasopalatine canal. This
      article describes a rare anatomical variation of the presence of a bilateral
      accessory canal extending from the nasal cavity lateral wall to an accessory
      foramen located on the hard palate, adjacent to the maxillary lateral incisor
      observed in cone beam computed tomography (CBCT) images. This case is an
      anatomical variation of the anterior superior alveolar nerve (canalis sinuosus).
      Identification of individual anatomical variations, especially on CBCT, may help
      the surgeon to avoid injuries to nerves during implant placement.

PMID- 22134776
TI  - Unusual branches of the proximal anterior cerebral artery.

PMID- 22134777
TI  - 2D-DIGE analysis of ovarian cancer cell responses to cytotoxic gold compounds.
AB  - Cytotoxic gold compounds hold today great promise as new pharmacological agents
      for treatment of human ovarian carcinoma; yet, their mode of action is still
      largely unknown. To shed light on the underlying molecular mechanisms, we
      performed 2D-DIGE analysis to identify differential protein expression in a
      cisplatin-sensitive human ovarian cancer cell line (A2780/S) following treatment
      with two representative gold(iii) complexes that are known to be potent
      antiproliferative agents, namely AuL12 and Au(2)Phen. Software analysis using
      DeCyder was performed and few differentially expressed protein spots were
      visualized between the three examined settings after 24 h exposure to the
      cytotoxic compounds, implying that cellular damage at least during the early
      phases of exposure is quite limited and selective, reflecting the attempts of the
      cell to repair damage and to survive the insult. The potential of novel proteomic
      methods to disclose mechanistic details of cytotoxic metallodrugs is herein
      further highlighted. Different patterns of proteomic changes were highlighted for
      the two metallodrugs with only a few perturbed protein spots in common. Using
      MALDI-TOF MS and ESI-Ion trap MS/MS, several differentially expressed proteins
      were identified. Two of these were validated by western blotting: Ubiquilin-1,
      responsible for inhibiting degradation of proteins such as p53 and NAP1L1, a
      candidate marker identified in primary tumors. Ubiquilin-1 resulted over
      expressed following both treatments and NAP1L1 was down-expressed in AuL12
      treated cells in comparison with control and with Au(2)Phen-treated cells. In
      conclusion, we performed a comprehensive analysis of proteins regulated by AuL12
      and Au(2)Phen, providing a useful insight into their mechanisms of action.

PMID- 22134778
TI  - Application of dissolution/permeation system for evaluation of formulation effect
      on oral absorption of poorly water-soluble drugs in drug development.
AB  - PURPOSE: The aim of the present study is to evaluate the formulation effect on
      the oral absorption of poorly water-soluble drugs using a dissolution/permeation
      system (D/P system). METHODS: This D/P system, consisting of apical and basal
      chambers and a Caco-2 cell monolayer mounted between chambers, can be used to
      perform simultaneous analysis of drug dissolution and permeation process of drugs
      applied as various dosage forms. Oral administration study with rats was also
      performed for both drugs as the same dosage forms. RESULTS: When danazol, a low
      soluble and high-permeable drug, was applied to the D/P system as various
      formulations, dissolved and permeated amounts were significantly high compared
      with those from a suspension form. On the other hand, whereas the dissolved
      amount of pranlukast, a low-soluble and low-permeable drug, was significantly
      increased by formulations, there were no significant changes observed in the
      permeated amount between suspension and formulation. The oral availability of
      danazol was significantly increased by formulations but not pranlukast, which
      corresponded well to in vitro evaluations. CONCLUSION: These results indicated
      that the D/P system might be applicable for selection of formulation on the basis
      of physicochemical drug properties.

PMID- 22134779
TI  - Fe3O4-PEI-RITC magnetic nanoparticles with imaging and gene transfer capability:
      development of a tool for neural cell transplantation therapies.
AB  - PURPOSE: To develop Fe(3)O(4)-PEI-RITC magnetic nanoparticles with multimodal MRI
      fluorescence imaging and transfection capability, for use in neural cell
      replacement therapies. METHODS: The Fe(3)O(4)-PEI-RITC MNPs were synthesised
      through a multi-step chemical grafting procedure: (i) Silanisation of MNPs with 3
      iodopropyltrimethoxysilane; (ii) PEI coupling with iodopropyl groups on the MNP
      surface; and (iii) RITC binding onto the PEI coating. The cell labelling and
      transfection capabilities of these particles were evaluated in astrocytes derived
      from primary cultures. RESULTS: Fe(3)O(4)-PEI-RITC MNPs did not exert acute toxic
      effects in astrocytes (at <= 6 days). Cells showed rapid and extensive particle
      uptake with up to 100% cellular labelling observed by 24 h. MRI and microscopy
      studies demonstrate that the particles have potential for use in bimodal MR
      fluorescence imaging. Additionally, the particles were capable of delivering
      plasmids encoding reporter protein (approximately 4 kb) to astrocytes, albeit
      with low efficiencies. CONCLUSIONS: Multifunctional Fe(3)O(4)-PEI-RITC MNPs were
      successfully prepared using a multi-step synthetic pathway, with the PEI and RITC
      chemically bound onto the MNP surface. Their combined MR-fluorescence imaging
      capabilities with additional potential for transfection applications can provide
      a powerful tool, after further development, for non-invasive cell tracking and
      gene transfer to neural transplant populations.

PMID- 22134780
TI  - Effects of iontophoresis and chemical enhancers on the transport of lidocaine and
      nicotine across the oral mucosa.
AB  - PURPOSE: To analyze the effects of chemical enhancers and iontophoresis on the
      buccal transmucosal delivery of lidocaine and nicotine. METHODS: Porcine oral
      mucosal samples were pretreated with chemical enhancers before conducting 8-hr
      Franz diffusion-cell experiments. In studies addressing the influence of
      iontophoresis on molecular transport, the current density was set at 0.3
      mA/cm(2). Data were analyzed using graphical and non-linear regression
      optimization techniques. RESULTS: Both permeation enhancement techniques promote
      drug transport. In the absence of electricity, the flux increased as high as 4-
      and 200-fold, relative to a control, in the case of lidocaine hydrochloride
      (LHCl) and nicotine hydrogen tartrate (NHT) gel formulations, respectively. The
      combination of iontophoresis and chemical enhancers produced an even higher flux
      compared to the original passive diffusion process: up to 8-fold for LHCl and 450
      fold for NHT. Mostly, the current helped to decrease the response time. However,
      a balance should be maintained between reaching a high delivery rate and reducing
      the time it takes to attain a desired flux value. In addition, the influence of
      chemical enhancers was drug-specific. CONCLUSIONS: The estimation of model
      parameters allows for a systematic approach to the design of chemical and
      physical penetration enhancers for transmucosal drug delivery.

PMID- 22134781
TI  - Fluorescence kinetic parameters and cyclic electron transport in guard cell
      chloroplasts of chlorophyll-deficient leaf tissues from variegated weeping fig
      (Ficus benjamina L.).
AB  - Residual chlorophyll in chlorophyll-deficient (albino) areas of variegated leaves
      of Ficus benjamina originates from guard cell chloroplasts. Photosynthetic
      features of green and albino sectors of F. benjamina were studied by imaging the
      distribution of the fluorescence decrease ratio Rfd within a leaf calculated from
      maximum (Fm) and steady-state leaf chlorophyll fluorescence (Fs) at 690 and 740
      nm. Local areas of albino sectors demonstrated an abnormally high
      Rfd(740)/Rfd(690) ratio. Fluorescence transients excited in albino sectors at red
      (640 and 690 nm) wavelengths showed an abrupt decrease of the Rfd values (0.4 and
      0.1, correspondingly) as compared with those excited at blue wavelengths (1.7
      2.4). This "Red Drop" was not observed for green sectors. Normal and chlorophyll
      deficient leaf sectors of F. benjamina were also tested for linear and cyclic
      electron transport in thylakoids. The tests have been performed studying
      fluorescence at a steady-state phase with CO(2)-excess impulse feeding,
      photoacoustic signal generated by pulse light source at wavelengths selectively
      exciting PSI, fluorescence kinetics under anaerobiosis and fluorescence changes
      observed by dual-wavelength excitation method. The data obtained for albino
      sectors strongly suggest the possibility of a cyclic electron transport
      simultaneously occurring in guard cell thylakoids around photosystems I and II
      under blue light, whereas linear electron transport is absent or insufficient.

PMID- 22134783
TI  - Establishment and characterization of a cell line, EH-GB2, derived from hepatic
      metastasis of gallbladder cancer.
AB  - Gallbladder cancer is a fatal neoplasia with an extremely low survival rate.
      Liver invasion and metastasis are the most common causes of death; however, the
      metastatic mechanism is still unclear, and no effective treatment methods are
      available. To provide comprehensive and profound approaches in investigating the
      metastatic mechanism and treatment methods, new cell lines derived from liver
      metastasis are urgently needed. A hepatic metastasis lesion was obtained from a
      65-year-old patient, and was treated using a primary culture method to establish
      a novel gallbladder cancer cell line. Different in vitro/in vivo methods were
      used to characterize the phenotypes of this cell line. The gallbladder cancer
      cell line was named EH-GB2, with a roughly 48-h doubling time. The cell line
      represents stronger colony formation and migration abilities than the control
      group. The cells showed complicated chromosomal abnormalities. EH-GB2 cells
      showed epithelial-to-mesenchymal transition (EMT) and the mRNA expression levels
      of E-cadherin and integrin were decreased, and those of vimentin, Snail, Twist,
      matrix metalloproteinase-1 (MMP-1) and MMP-2 were increased in comparison with
      control cells. The in vivo study demonstrated that EH-GB2 cells show significant
      tumorigenicity in nude mice. The EH-GB2 established gallbladder cancer cell line
      is useful for future studies of gallbladder cancer development, progression,
      metastasis and therapy.

PMID- 22134784
TI  - An integrated alcohol abuse and medical treatment model for patients with
      hepatitis C.
AB  - BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection have high
      rates of alcohol consumption, which is associated with progression of fibrosis
      and lower response rates to HCV treatment. AIMS: This prospective cohort study
      examined the feasibility of a 24-week integrated alcohol and medical treatment to
      HCV-infected patients. METHODS: Patients were recruited from a hepatology clinic
      if they had an Alcohol Use Disorders Identification Test score >4 for women and
      >8 for men, suggesting hazardous alcohol consumption. The integrated model
      included patients receiving medical care and alcohol treatment within the same
      clinic. Alcohol treatment consisted of 6 months of group and individual therapy
      from an addictions specialist and consultation from a study team psychiatrist as
      needed. RESULTS: Sixty patients were initially enrolled, and 53 patients
      participated in treatment. The primary endpoint was the Addiction Severity Index
      (ASI) alcohol composite scores, which significantly decreased by 0.105 (41.7%
      reduction) between 0 and 3 months (P < 0.01) and by 0.128 (50.6% reduction)
      between 0 and 6 months (P < 0.01) after adjusting for covariates. Alcohol
      abstinence was reported by 40% of patients at 3 months and 44% at 6 months.
      Patients who did not become alcohol abstinent had reductions in their ASI alcohol
      composite scores from 0.298 at baseline to 0.219 (26.8% reduction) at 6 months (P
      = 0.08). CONCLUSION: This study demonstrated that an integrated model of alcohol
      treatment and medical care could be successfully implemented in a hepatology
      clinic with significant favorable impact on alcohol use and abstinence among
      patients with chronic HCV.

PMID- 22134785
TI  - Efficacy of entecavir and adefovir combination therapy for patients with
      lamivudine- and entecavir-resistant chronic hepatitis B.
AB  - BACKGROUND: The optimal treatment of patients with chronic hepatitis B (CHB) who
      develop resistance to both lamivudine (LMV) and entecavir (ETV) after sequential
      monotherapy of LMV and ETV remains little known. METHODS: We evaluated the
      efficacy of entecavir (ETV) plus adefovir dipivoxil (ADV) combination therapy for
      patients with resistance to LMV and ETV. We reviewed the medical records of 12
      patients, and treated all 12 patients with ETV plus ADV combination therapy for
      at least 18 months. Quantitative hepatitis B virus (HBV) DNA levels, serologic
      markers, and hepatic panel values were monitored at baseline and 3-month
      intervals thereafter for 18 months. RESULTS: The baseline mean serum HBV DNA
      level was 7.26 +/- 1.11 log(10) copies/ml. The mean reductions in serum HBV DNA
      levels from baseline to 3, 6, 9, 12, 15, and 18 months were -1.98 +/- 1.03, -2.87
      +/- 1.02, -3.32 +/- 1.10, -3.92 +/- 1.30, -4.36 +/- 1.22, and -4.57 +/- 1.18
      log(10) copies/ml, respectively. Complete virological response (HBV DNA of <2
      log(10) copies/ml) at 6, 12, and 18 months was observed in 1 (8.3%), 4 (33.3%),
      and 6 (50.0%) patients, respectively. The 2 patients with baseline HBV DNA of <6
      log(10) copies/ml achieved complete virological response at 18 months, while 4 of
      10 patients with baseline HBV DNA of >=6 log(10) copies/ml achieved complete
      virological response at 18 months. None of the 12 patients experienced
      virological breakthrough during follow-up. CONCLUSIONS: ETV plus ADV combination
      therapy effectively reduced serum HBV DNA levels in patients with CHB who
      developed resistance to both LMV and ETV. Additional long-term studies are needed
      to assess the effect of long-term treatment with these drugs.

PMID- 22134786
TI  - Inactivation of MYO5B promotes invasion and motility in gastric cancer cells.
AB  - BACKGROUND: Loss of cell polarity and tissue disorganisation are hallmarks of
      cancer. MYO5B mutations disrupt epithelial cell polarity, suggesting that MYO5B
      may be involved in tumorigenesis. METHODS: We analyzed MYO5B expression in 70
      gastric cancer tissues by immunohistochemistry using a tissue microarray method.
      Two related proteins, Rab11a and TfR, were also investigated. RESULTS: We found
      that the negative rate of MYO5B was 78.6 and 17.1% in gastric cancer and normal
      gastric tissues (P < 0.001), respectively. The MYO5B expression had a strong
      relationship with Rab11a expression (P = 0.002). We also found that inactivation
      by siRNA against MYO5B promoted the proliferation, invasion and migration of
      gastric cancer cells. CONCLUSION: The expression of MYO5B was downregulated in
      gastric cancer and inactivation of MYO5B may contribute to tumorigenesis.
      Therefore, MYO5B may become an important biomarker for gastric cancer in the
      future.

PMID- 22134787
TI  - Transient PPI responsive esophageal eosinophilia may be a clinical sub-phenotype
      of pediatric eosinophilic esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) and gastroesophageal reflux (GERD)
      both cause esophageal eosinophilia. Reports show that esophageal eosinophilia
      meeting criteria for EoE may respond to acid suppression mono-therapy. Consensus
      guidelines have termed this entity "PPI-responsive esophageal eosinophilia"
      (PPIRee) and recommend a trial with proton-pump inhibitors (PPIs) prior to a
      definitive EoE diagnosis. The mechanisms of PPIRee and whether this represents a
      sub-phenotype of GERD, a sub-phenotype of EoE, or its own distinct entity remain
      unclear. METHODS: A database search revealed children who had an initial
      histologic response to PPI monotherapy but had recurrence of esophageal
      eosinophilia and symptoms despite continued PPI therapy. In order to understand
      the patterns of esophageal inflammatory cells during PPI therapy we performed
      quantitative immunohistochemistry for mast cells, CD1a positive antigen
      presenting cells, and CD45RO memory T cells. RESULTS: Four pediatric patients
      (mean age 9.5 years) had a mean peak eosinophil count of 52 eos/hpf which
      initially resolved completely during PPI mono-therapy. However, despite continued
      PPI therapy, endoscopic abnormalities and pan-esophageal eosinophilia recurred
      (mean peak eosinophil count of 64 eos/hpf). There was no seasonal variation or
      lack of PPI adherence that explained the return of eosinopihlia. Similar to
      eosinophilia, mastocytosis and CD45RO cells were transiently decreased during PPI
      therapy. CONCLUSION: PPIs appear to be capable of transiently resolving multiple
      inflammatory cell subsets including eosinophils, mast cells, and CD45RO cells.
      Our data suggest that patients with PPIRee should have continued monitoring for
      EoE during PPI monotherapy. The numbers of patients in whom PPIRee is a transient
      phenomenon and whether PPIRee represents a sub-phenotype of EoE in children
      merits further investigation.

PMID- 22134788
TI  - New therapeutic approaches to spinal muscular atrophy.
AB  - Bench to bedside progress has been widely anticipated for a growing number of
      neurodegenerative disorders. Of these, spinal muscular atrophy (SMA) is perhaps
      the best poised to capitalize on advances in targeted therapeutics development
      over the next few years. Several laboratories have achieved compelling success in
      SMA animal models using sophisticated methods for targeted delivery, repair, or
      increased expression of the survival motor neuron protein, SMN. The clinical
      community is actively collaborating to identify, develop, and validate outcome
      measures and biomarkers in parallel with laboratory efforts. Innovative trial
      design and synergistic approaches to maximize proactive care in conjunction with
      treatment with one or more of the promising pharmacologic and biologic therapies
      currently in the pipeline will maximize our chances to achieve meaningful
      outcomes for patients. This review highlights recent promising scientific and
      clinical advances bringing us ever closer to effective treatment(s) for our
      patients with SMA.

PMID- 22134789
TI  - 2-Triazenoazaindoles: alpha novel class of triazenes inducing transcriptional
      down-regulation of EGFR and HER-2 in human pancreatic cancer cells.
AB  - Pancreatic cancer is a complex malignancy arising from the accumulation of
      genetic and epigenetic defects in the affected cells. Standard chemotherapy for
      patients with advanced disease shows only modest effects and is associated with
      considerable toxicity. Overexpression or aberrant activation of members of the
      epidermal growth factor receptor tyrosine kinase family, which includes EGFR and
      HER-2, occurs frequently and is associated with multiple drug resistance and
      decreased patient survival. In this study, we have investigated the therapeutic
      potential of AS104, a novel compound of the triazene class, with potential
      inhibitory effects on EGFR. We found that treatment of cells with AS104 causes
      significant reduction of cell growth and metabolic activity in four human
      pancreatic cancer cell lines. Furthermore, we show that the AS104-mediated
      induction of apoptotic cell death is associated with stimulation of autophagy in
      a dose-dependent manner. Treatment of cells with AS104 results in significant
      down-regulation of EGFR and HER-2 expression and activity and subsequent
      inhibition of downstream signaling proteins. Quantitative RT-PCR analysis and
      assays with proteasome inhibitors revealed that AS104 regulates the expression of
      EGFR and HER-2 at the transcriptional level. These findings provide for the first
      time experimental evidence for efficacy of AS104 in the simultaneous
      transcriptional repression of EGFR and HER-2 genes and suggest that AS104 may
      have therapeutic potential in the treatment of pancreatic cancers that express
      high levels of the aforementioned receptor tyrosine kinases.

PMID- 22134790
TI  - Laser treatment for retinopathy of prematurity.
AB  - Retinal development involves a complex coordination of events that may be
      affected by premature delivery, leading to retinopathy of prematurity (ROP), a
      potential blinding childhood disease. The avascular retina drives further disease
      progression, with laser ablation reducing unfavorable anatomic outcomes as well
      as maintaining visual acuity. Trials have stressed the importance of early
      identification and treatment of threshold and high-risk prethreshold disease to
      improve outcomes. Retinal ablation with laser photocoagulation should involve
      entire treatment of avascular retina with a confluent laser spot density,
      avoiding skip lesions. The current review highlights the use of laser
      photocoagulation in the treatment of ROP.

PMID- 22134791
TI  - Environmental factors associated with Crohn's disease in India-there's more to it
      than meets the eye.

PMID- 22134792
TI  - Sleep as a window into the world of fibromyalgia syndrome.

PMID- 22134793
TI  - Pragmatic decisions over nonsteroidal antiinflammatory drug treatment in
      osteoarthritis--continuous versus intermittent.

PMID- 22134794
TI  - Philip S. Hench's rheumatology axiomatic generalizations.
AB  - Philip S. Hench, MD, the first Mayo Clinic rheumatologist, came to Mayo Clinic in
      1921. Because of his efforts in patient care, education, and research, and those
      of his colleagues, Mayo Clinic has been considered the first academic
      rheumatology center established in the United States. An early, popular lecture
      he gave to the internal medicine residents was an important and unique part of
      the rheumatology education program and was entitled "Axiomatic Generalizations
      Useful in the Diagnosis of Rheumatic Diseases." We review the axioms in light of
      the status of rheumatology in the 1920s and 1930s when they were written, and
      assess their relevance today, 70 to 80 years later.

PMID- 22134795
TI  - Atypical femoral fractures in patients taking longterm alendronate.

PMID- 22134796
TI  - Necrotic tongue: a rare manifestation of giant cell arteritis.

PMID- 22134797
TI  - Rapid progressive cerebral atrophy in systemic lupus erythematosus.

PMID- 22134798
TI  - Inflammatory back pain in patients treated with isotretinoin.

PMID- 22134799
TI  - Preliminary evidence that subclinical enthesopathy may predict psoriatic
      arthritis in patients with psoriasis.

PMID- 22134800
TI  - Articular involvement in disseminated histoplasmosis in a kidney transplant
      patient taking azathioprine.

PMID- 22134803
TI  - Complete and incomplete Kawasaki disease: two sides of the same coin.
AB  - We sought to determine differences in clinical presentation, treatment response
      and coronary artery outcomes between complete and incomplete KD. All patients
      treated for KD between January 1990 and April 2007 were reviewed. Patients were
      classified as having an incomplete presentation if presenting with fever >= 5
      days and <4 "classic" KD clinical signs. A total of 955 patients were included.
      Incomplete clinical presentation was seen in 217 cases (23%). Patient's
      demographic, clinical and laboratory characteristics were similar between groups
      with few exceptions. Patients presenting with incomplete KD had a longer median
      interval from symptom onset to diagnosis (7 [4-17] versus 6 [6-13] days, p <
      0.001) and were less likely to be treated with intravenous immunoglobulin (86%
      versus 96%, p < 0.001). No significant difference between groups were seen in
      regard to coronary artery abnormalities (incomplete 13% versus complete 11%, p =
      0.58). CONCLUSION: Complete and incomplete KD appear to be different sides of the
      same coin, differing only in the number of signs and symptoms at presentation.
      Similar laboratory findings and coronary artery outcomes between the two groups
      support this conclusion.

PMID- 22134804
TI  - Vit B12 treatment.

PMID- 22134805
TI  - Late-onset neonatal infections: incidences and pathogens in the era of antenatal
      antibiotics.
AB  - Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced
      the incidence of early-onset neonatal infection (EONI); however, little is known
      about the effects of increased maternal exposure to antibiotics on late-onset
      neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our
      region after the application of French recommendations and to determine whether
      LONI-causing organisms and their antibiotic susceptibility are influenced by
      peripartum antibiotic exposure. We performed a prospective epidemiologic study of
      139 confirmed and possible cases of bacterial LONI in patients treated with
      antibiotics for at least 5 days of the 22,458 infants born in our region in the
      year 2007. The overall incidence of LONI caused by all pathogens, Group B
      streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72,
      respectively, per 1,000 live births. Our findings revealed three major types of
      LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase
      negative Staphylococcus septicemia affecting preterm infants, and GBS infections
      with severe clinical presentation. Univariable analysis revealed that maternal
      antibiotic exposure was significantly associated with the risk of amoxicillin
      resistant E. coli infection (p = 0.01). Postnatal antibiotic exposure was
      associated with an increased risk of E. coli LONI (p = 0.048). This link
      persisted upon multivariable analysis; however, no additional risk factors were
      identified for LONI caused by antibiotic-resistant E. coli. CONCLUSION: Our
      findings confirm that despite the benefits of antenatal antibiotics, this
      treatment can increase the risk of antibiotic-resistant cases of LONI. National
      and international surveillance of LONI epidemiology is essential to assess
      benefits and potential negative consequences of perinatal antibiotic exposure.

PMID- 22134806
TI  - Evaluation of patients' and physicians' expectations and attributes of
      osteoarthritis treatment using Kano methodology.
AB  - PURPOSE: To evaluate expectations regarding osteoarthritis (OA) treatment of
      patients (PT) and physicians (PH) (Orthopedic Surgeons) in Spain. METHODS:
      Multicenter, cross-sectional study in adult patients with OA with at least 1 year
      of disease progression and with at least one prescription of anti-inflammatory
      drugs within the last year. Sociodemographic, clinical, and treatment
      characteristics as well as patient-reported outcomes were obtained by phone
      interview. Using a treatment expectations questionnaire and applying Kano
      methodology, treatment attributes were classified as: must-be; one-directional;
      attractive; indifferent; reverse or questionable. RESULTS: A total of 965 adult
      patients with OA [mean age: 64 years (SD: 11); 75% women] and 383 PH [mean age:
      47 years (SD: 10); 14% women] were surveyed. None of the treatment attributes
      showed a dominant "must-be" characteristic. The attributes that led to a greater
      dissatisfaction when absent were non-occurrence of long-term adverse effects, no
      discomfort upon administration, and achievement of symptoms relief. The two
      attributes that were considered most important by PT were as follows: achievement
      of both total disappearance of the symptoms and lasting symptom relief.
      Conversely, for PH, the two most important attributes were related to short- and
      long-term safety. CONCLUSIONS: A clear different perspective regarding treatment
      expectation was noted among PT (effectiveness) and PH (safety). Therefore, when
      selecting the most appropriate treatment for OA, PH should invite PT to
      participate in the decision making.

PMID- 22134807
TI  - The effect of amino acid combinations on the development of tissues of different
      origins in an organotypic culture.

PMID- 22134808
TI  - Neurotropic activity of ACTH(7-10)PGP, an analog of an ACTH fragment.

PMID- 22134809
TI  - Cardiorespiratory changes in beluga in response to acoustic noise.

PMID- 22134810
TI  - Neurophysiological mechanisms of inhibition and disinhibition in processing of
      cognitive information.

PMID- 22134811
TI  - Dopamine synthesis in the nigrostriatal system at the presymptomatic and early
      symptomatic stages in parkinsonian mice.

PMID- 22134812
TI  - Molecular genetic and culture diagnosis of Mycoplasma in fish family Thymallidae.

PMID- 22134813
TI  - The role of trematode infestation in the specifics of skeleton morphogenesis of
      Rana arvalis Nilsson, 1842.

PMID- 22134814
TI  - Virioplankton and bacterioplankton of the high-mountain Lake Hovsgol (Mongolia).

PMID- 22134815
TI  - Spleen hypertrophy in small mammals: an ecological and histological analysis.

PMID- 22134816
TI  - Interspecific competition of symbiotic and fouling species of red king crab in
      the Barents Sea.

PMID- 22134817
TI  - New data characterizing the metabolic status of hooded (Cystophora cristata
      Erxleben, 1777) and harp (Pagophilus groenlandica Erxleben, 1777) seals in the
      early postnatal period of development.

PMID- 22134818
TI  - The effect of natural and synthetic antimutagens in human radiosensitive cells
      differing in genetic polymorphism.

PMID- 22134819
TI  - The peculiarities of the helminth fauna of herring gulls of the synanthropic
      Murmansk population.

PMID- 22134820
TI  - A novel type of polychaete coelomocytes found in Ophelia limacina (Rathke, 1843).

PMID- 22134821
TI  - Regenerative capacity of the eye of Helix lucorum in a 163-day orbital flight
      aboard the International Space Station.

PMID- 22134822
TI  - Structure of ripe oocytes of the Sakhalin sturgeon Acipenser mikadoi.

PMID- 22134823
TI  - The role of parasites in symbiotic associations of coral fish.

PMID- 22134824
TI  - Iron nanoparticles as a food additive for poultry.

PMID- 22134825
TI  - Influence of acoustic noises on the white whale hearing thresholds.

PMID- 22134826
TI  - Response to overheating in spiny mice (the genus Acomys) from arid regions in
      northwestern Ethiopia.

PMID- 22134827
TI  - Neoplasms in the swim bladder of juvenile cod.

PMID- 22134828
TI  - Influence of reproductive hormones on the induction of CD4(+)CD25 (bright)Foxp
      (3+) regulatory T cells.

PMID- 22134829
TI  - Simvastatin inhibits cancer cell growth by inducing apoptosis correlated to
      activation of Bax and down-regulation of BCL-2 gene expression.
AB  - The statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have
      been proven to be effective in lowering cholesterol and as anti-lipid agents
      against cardiovascular disease. Recent reports demonstrate an anticancer effect
      induced by the statins through inhibition of cell proliferation. Probably, these
      effects are due to suppression of the mevalonate pathway leading to the depletion
      of various downstream products that play an essential role in cell cycle
      progression, cell signaling and membrane integrity. To date, although many
      hypotheses have been proposed, the exact mechanism at the basis of cancer cell
      growth arrest induced by statins is not known. In this study, we have
      demonstrated that simvastatin, at a dose of 20 uM for 24-72 h, induced in cancer
      cells but not in normal cells precise features of apoptosis including increased
      DNA fragmentation while, at the molecular level simvastatin induced
      overexpression of the pro-apoptotic gene Bax together with an inhibition of BCL
      2, the gene that has the well-known function of protecting cells from apoptosis.
      The simvastatin-mediated induction of apoptosis in similar cancer cells but not
      in normal cells is very interesting and may be at the basis of cancer therapy
      using statins, usually in combination with chemotherapy or to be used as a cancer
      protective drug. Simvastatin may, thus, play a dual prophylactic role as a lipid
      lowering drug for the prevention of heart disease and as an anticancer agent to
      prevent certain types of cancers.

PMID- 22134830
TI  - Anti-thrombin-III reduction and posterior reversible encephalopathy syndrome
      (PRES) in acute lymphoblastic leukaemia (ALL). New insight into PRES
      pathophysiology.

PMID- 22134831
TI  - Aberrant expression of myeloid and B cell markers in an aggressive multiple-site
      myeloid sarcoma.

PMID- 22134832
TI  - Perfluoroalkyl compounds (PFCs) in wildlife from an urban estuary.
AB  - Previous research has documented the bioaccumulation of perfluoroalkyl compounds
      (PFCs) in apex predators in remote locations but few studies have evaluated urban
      estuaries. To assess the importance of PFCs in San Francisco Bay, two apex
      predators in the San Francisco Bay, double-crested cormorants (Phalacrocorax
      auritus) and Pacific harbor seals (Phoca vitulina richardii), were sampled. Prey
      fish (Atherinops affinis and Menidia audens) were also evaluated to better
      understand potential sources of PFCs to the foodweb. Perfluorooctane sulfonate
      (PFOS) was the primary PFC detected in cormorant eggs, small fish and harbor seal
      serum. PFOS detected in San Francisco Bay seal serum was typically an order of
      magnitude higher than those at the reference site. PFOS concentrations were
      highest in seals and cormorant eggs from the highly urbanized southern portion of
      the Bay. PFOS in eggs from the southern part of the Bay remained relatively
      constant between 2006 and 2009 despite the phase-out of perfluorosulfonyl-based
      compounds nationally. In addition, these levels exceed the avian predicted no
      effects concentration of 1.0 MUg mL(-1). Concentrations of the remaining PFCs
      measured were substantially lower than those of PFOS.

PMID- 22134833
TI  - COL4A1 mutations associated with a characteristic pattern of intracranial
      calcification.
AB  - Intracranial calcification (ICC) is a relatively common radiological finding in
      children undergoing investigation for neurological disorders. Many causes are
      recognised, and ICC is often regarded as a non-specific sign.From an ongoing
      study of ICC, we identified 5 patients with characteristic radiological features,
      in whom a mutation in the COL4A1 gene was found.All patients had CT and MR
      imaging. MR images demonstrated features of periventricular leukomalacia with
      irregular dilatation of the lateral ventricles with or without porencephaly, loss
      of hemispheric white matter volume, and high signal on T2 and FLAIR sequences
      within periventricular and deep white matter. Calcification was apparent on MR in
      4 patients. CT scans demonstrated spot and linear calcification in the
      subependymal region and around areas of porencephaly. Calcification was also
      visible in the deep cerebral white matter and basal ganglia. 1 patient showed
      calcification in the central pons.ICC occurs in COL4A1-related disease. The
      radiological features are distinct from other conditions demonstrating
      recognisable patterns of ICC, such as congenital cytomegalovirus infection and
      Aicardi-Goutieres syndrome. In the absence of a known risk factor for
      periventricular leukomalacia, the presence of these radio-logical findings should
      suggest the possibility of COL4A1-related disease.

PMID- 22134835
TI  - Time-lapse imaging of granule cells in mouse entorhino-hippocampal slice cultures
      reveals changes in spine stability after entorhinal denervation.
AB  - Principal neurons that are partially denervated after brain injury remodel their
      synaptic connections and show biphasic changes in their dendritic spine density:
      during an early phase after denervation spine density decreases and during a late
      phase spine density recovers again. It has been hypothesized that these changes
      in spine density are caused by a period of increased spine loss followed by a
      period of increased spine formation. We have tested this hypothesis, which is
      based on data from fixed tissues, by using time-lapse imaging of denervated
      dentate granule cells in organotypic entorhino-hippocampal slice cultures of Thy1
      GFP mice. Our data show that nondenervated granule cells turn over spines
      spontaneously while keeping their spine density constant. Denervation influenced
      this equilibrium and induced biphasic changes in the spine loss rate but not in
      the rate of spine formation: during the early phase after denervation the spine
      loss rate was increased and during the late phase after denervation the spine
      loss rate was decreased compared with nondenervated control cultures. In line
      with these observations, time-lapse imaging of identified spines formed after the
      lesion revealed that the stability of these spines was decreased during the early
      phase and increased during the late phase after the lesion. We conclude that
      biphasic changes in spine loss rate and spine stability but not in the rate of
      spine formation play a central role in the reorganization of dentate granule
      cells after entorhinal denervation in vitro.

PMID- 22134834
TI  - Radiation therapy in the prevention of brain metastases.
AB  - Over 150,000 cancer patients will be diagnosed with brain metastases this year
      alone. Survival for those diagnosed with brain metastases remains poor despite
      multimodality management with surgery, chemotherapy, and radiation. Preventative
      strategies to mitigate brain metastases have met with mixed results. In leukemia
      and small cell lung cancer there are defined roles for preventative radiation to
      be delivered, which can result in improved local control and survival. There is a
      less defined role for preventative radiation in locally advanced non-small cell
      lung cancer and budding interest for radiation prevention in breast cancer. The
      potential impact preventative cranial irradiation may have on neurocognitive
      function and quality of life needs to be considered prior to its administration.

PMID- 22134836
TI  - Comparative analysis of pre-replication complex proteins in transformed and
      normal cells.
AB  - This study examines the abundance of the major protein constituents of the pre
      replication complex (pre-RC), both genome-wide and in association with specific
      replication origins, namely the lamin B2, c-myc, 20mer1, and 20mer2 origins.
      Several pre-RC protein components, namely ORC1-6, Cdc6, Cdt1, MCM4, MCM7, as well
      as additional replication proteins, such as Ku70/86, 14-3-3, Cdc45, and PCNA,
      were comparatively and quantitatively analyzed in both transformed and normal
      cells. The results show that these proteins are overexpressed and more abundantly
      bound to chromatin in the transformed compared to normal cells. Interestingly,
      the 20mer1, 20mer2, and c-myc origins exhibited a two- to threefold greater
      origin activity and a two- to threefold greater in vivo association of the pre-RC
      proteins with these origins in the transformed cells, whereas the origin
      associated with the housekeeping lamin B2 gene exhibited both similar levels of
      activity and in vivo association of these pre-RC proteins in both cell types.
      Overall, the results indicate that cellular transformation is associated with an
      overexpression and increased chromatin association of the pre-RC proteins. This
      study is significant, because it represents the most systematic comprehensive
      analysis done to date, using multiple replication proteins and different
      replication origins in both normal and transformed cell lines.

PMID- 22134837
TI  - Shorter disease-specific survival of ER-positive breast cancer patients with high
      cytoplasmic Src kinase expression after tamoxifen treatment.
AB  - BACKGROUND: Src kinase, a non-receptor tyrosine kinase, is overexpressed and
      highly activated in a number of human cancers and appears to show a significant
      relationship with breast cancer progression. Recent in vitro studies have
      suggested that Src kinase may be involved in tamoxifen resistance. METHODS:
      Immunohistochemistry was performed on 392 resected breast cancers using an
      antibody to c-Src. Expression was assessed using the weighted histoscore method.
      RESULTS: Forty-five percentage of breast tumours exhibited nuclear, 46%
      cytoplasmic and 7% membrane expression. Lymph node positivity correlated with
      cytoplasmic c-Src tumour expression levels (P < 0.001). Nuclear c-Src correlated
      negatively with cytoplasmic and membrane c-Src expression (P < 0.001, P = 0.005).
      High expression levels of cytoplasmic c-Src was associated with worse disease
      specific survival (P = 0.026) after completing 5 years of tamoxifen therapy.
      However, high expression of c-Src at any cellular location did not show any
      association with de novo relapse on tamoxifen (c-Src nuc P = 0.906, c-Src cyto P
      = 0.735 and c-Src memb P = 0.791). CONCLUSIONS: No translational evidence was
      found in this study to support a role for Src kinase in developing de novo
      tamoxifen resistance. However, based on our findings on late clinical outcome,
      patients with high cytoplasmic c-Src may be selected for continuing endocrine
      therapy to prevent worsening prognosis.

PMID- 22134838
TI  - Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus
      thalidomide and prednisone in prostate cancer patients.
AB  - PURPOSE: The aim of this study was to evaluate clinical outcomes of second-line
      chemotherapy with capecitabine and cyclophosphamide (CTX) plus thalidomide and
      prednisone in refractory advanced castrate-resistant prostate cancer (CRPC)
      patients. METHODS: We retrospectively reviewed patients with advanced CRPC who
      had previously progressed to first-line docetaxel-based chemotherapy. Patients
      were given second-line chemotherapy with capecitabine and CTX plus thalidomide
      and prednisone throughout the course. Patients were evaluated for response and
      toxicity, and treatment was continued until the disease progression or excessive
      toxicity was noted. RESULTS: From April 2007 to February 2010, a total of 28
      patients (median age, 72.8 +/- 2.9 years) received second-line chemotherapy. The
      median cycle and duration of metronomic chemotherapy were six (range: 1-12)
      cycles and 6.3 (range 1.5-20.5) months, respectively. Prostatic-specific antigen
      was decreased by more than 50% in 10 (35.7%) of the 28 patients. All patients had
      bone metastases, and 8 patients (28.6%) had measurable soft tissue lesions. Among
      the 8 patients, 1 patient achieved partial response, and 3 patients had
      stabilized disease. With a median follow-up time of 29.5 (95% CI, 26.4-33.4)
      months, median composite progression-free survival and overall survival were 4.7
      (95% CI, 3.4-5.7) months and 19.5 (95% CI, 18.9-25.5) months, respectively. No
      grade 3-4 toxicity was observed, and none of the patients experienced grade 3-4
      hematological and nonhematological toxicities. CONCLUSIONS: These data suggested
      that oral combination second-line chemotherapy with capecitabine and CTX plus
      thalidomide and prednisone offers promising activity with an excellent safety
      profile for patients with advanced CRPC.

PMID- 22134839
TI  - Effect of bile acid sequestrants on glucose metabolism, hepatic de novo
      lipogenesis, and cholesterol and bile acid kinetics in type 2 diabetes: a
      randomised controlled study.
AB  - AIMS/HYPOTHESIS: The primary aim of this completed multicentre randomised,
      parallel, double-blind placebo-controlled study was to elucidate the mechanisms
      of glucose-lowering with colesevelam and secondarily to investigate its effects
      on lipid metabolism (hepatic de novo lipogenesis, cholesterol and bile acid
      synthesis). METHODS: Participants with type 2 diabetes (HbA(1c) 6.7-10.0% [50-86
      mmol/mol], fasting glucose <16.7 mmol/l, fasting triacylglycerols <3.9 mmol/l and
      LDL-cholesterol >1.55 mmol/l) treated with diet and exercise, sulfonylurea,
      metformin or a combination thereof, were randomised by a central coordinator to
      either 3.75 g/day colesevelam (n = 30) or placebo (n = 30) for 12 weeks at three
      clinical sites in the USA. The primary measure was the change from baseline in
      glucose kinetics with colesevelam compared to placebo treatment. Fasting and
      postprandial glucose, lipid and bile acid pathways were measured at baseline and
      post-treatment using stable isotope techniques. Plasma glucose, insulin, total
      glucagon-like peptide-1 (GLP-1), total glucose-dependent insulinotropic
      polypeptide (GIP), glucagon and fibroblast growth factor-19 (FGF-19)
      concentrations were measured during the fasting state and following a meal
      tolerance test. Data was collected by people blinded to treatment. RESULTS:
      Compared with placebo, colesevelam improved HbA(1c) (mean change from baseline of
      0.3 [SD 1.1]% for placebo [n = 28] and -0.3 [1.1]% for colesevelam [n = 26]),
      glucose concentrations, fasting plasma glucose clearance and glycolytic disposal
      of oral glucose. Colesevelam did not affect gluconeogenesis or appearance rate
      (absorption) of oral glucose. Fasting endogenous glucose production and
      glycogenolysis significantly increased with placebo but were unchanged with
      colesevelam (treatment effect did not reach statistical significance). Compared
      with placebo, colesevelam increased total GLP-1 and GIP concentrations and
      improved HOMA-beta cell function while insulin, glucagon and HOMA-insulin
      resistance were unchanged. Colesevelam increased cholesterol and bile acid
      synthesis and decreased FGF-19 concentrations. However, no effect was seen on
      fractional hepatic de novo lipogenesis. CONCLUSIONS/INTERPRETATION: Colesevelam,
      a non-absorbed bile acid sequestrant, increased circulating incretins and
      improved tissue glucose metabolism in both the fasting and postprandial states in
      a manner different from other approved oral agents. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00596427 FUNDING: The study was funded by Daiichi Sankyo.

PMID- 22134841
TI  - Charlson comorbidity score is a strong predictor of mortality in hemodialysis
      patients.
AB  - PURPOSE: The Charlson comorbidity index (CCI) is a commonly used scale for
      assessing morbidity, but its role in assessing mortality in hemodialysis patients
      is not clear. Age, a component of CCI, is a strong risk factor for morbidity and
      mortality in chronic diseases and correlates with comorbidities. We hypothesized
      that the Charlson comorbidity index without age is a strong predictor of
      mortality in hemodialysis patients. METHODS: A 6-year cohort of 893 hemodialysis
      patients was examined for an association between a modified CCI (without age and
      kidney disease) (mCCI) and mortality. RESULTS: Patients were 53+/-15 years old
      (mean+/-SD), had a median mCCI score of 2, and included 47% women, 31% African
      Americans and 55% diabetics. After adjusting for case-mix and nutritional and
      inflammatory markers including C-reactive protein and interleukin-6, 2nd (mCCI: 1
      2), 3rd (mCCI=3), and 4th (mCCI: 4-9) quartiles compared to 1st (mCCI=0)
      quartiles showed death hazard ratios (95% confidence intervals) of 1.43 (0.92
      2.23), 1.70 (1.06-2.72), and 2.33 (1.43-3.78), respectively. The mCCI-death
      association was robust in non-African Americans. The CCI-death association
      linearity was verified in cubic splines. Each 1 unit higher mCCI score was
      associated with a death hazard ratio of 1.16 (1.07-1.27). CONCLUSIONS: CCI
      independent of age is a robust and linear predictor of mortality in hemodialysis
      patients, in particular in non-African Americans.

PMID- 22134840
TI  - Retinopathy in old persons with and without diabetes mellitus: the Age,
      Gene/Environment Susceptibility--Reykjavik Study (AGES-R).
AB  - AIMS/HYPOTHESIS: We aimed to describe the prevalence of retinopathy in an aged
      cohort of Icelanders with and without diabetes mellitus. METHODS: The study
      population consisted of 4,994 persons aged >= 67 years, who participated in the
      Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-R). Type 2 diabetes
      mellitus was defined as HbA(1c) >= 6.5% (>48 mmol/mol). Retinopathy was assessed
      by grading fundus photographs using the modified Airlie House adaptation of the
      Early Treatment Diabetic Retinopathy Study protocol. Associations between
      retinopathy and risk factors were estimated using odds ratios obtained from
      multivariate analyses. RESULTS: The overall prevalence of retinopathy in AGES-R
      was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom
      gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2,
      31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had
      proliferative retinopathy. Clinically significant macular oedema was present in
      five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in
      diabetic patients in a multivariate model included HbA(1c), insulin use and use
      of oral hypoglycaemic agents, the last two being indicators of longer disease
      duration. In 4478 participants without diabetes mellitus, gradable fundus photos
      were available for 4,453 participants, with retinopathy present in 476 (10.7%,
      95% CI 9.8, 11.6) and clinically significant macular oedema in three persons.
      Independent risk factors included increasing age and microalbuminuria.
      CONCLUSIONS/INTERPRETATION: Over three-quarters (78%) of retinopathy cases were
      found in persons without diabetes and a strong association between
      microalbuminuria and non-diabetic retinopathy was found. These results may have
      implications for patient management of the aged.

PMID- 22134843
TI  - Atypical presentation of Kawasaki disease in young infants mimicking a
      retropharyngeal abscess.

PMID- 22134842
TI  - Abdominal gunshot wounds: multi-detector-row CT findings compared with
      laparotomy: a prospective study.
AB  - The purpose of this study was to access the accuracy of multi-detector-row
      computed tomography (MDCT) in diagnosing injuries in hemodynamically stable
      abdominal gunshot wound victims (AGWV). Triple-contrast MDCT was performed in
      hemodynamically stable AGWV during a 20-month prospective diagnostic accuracy
      study. Thirty-one patients (30 males, 1 female; mean age, 24.3 years) were
      evaluated by two radiologists for evidence of injury to solid and hollow organs,
      vascular structures, urinary bladder, diaphragm, fractures, and general findings
      (free fluid, pneumoperitoneum, and mesentery lesions). All of the patients
      underwent laparotomy, and prevalence, sensitivity, specificity, accuracy, and
      positive and negative predictive values were calculated. No statistically
      significant differences between radiologists were found. All of the solid and
      hollow organ lesions, vascular lesions, and general findings were detected. One
      of the four urinary bladder lesions was missed by MDCT, leading in this case to a
      sensitivity of 75%, specificity of 100%, positive predictive value of 100%,
      negative predictive value of 96.4%, and accuracy of 96.8% (p = 0.001). One of the
      eight diaphragm lesions was missed by MDCT, and its sensitivity was 87.5%,
      specificity was 100%, positive predictive value was 100%, negative predictive
      value was 95.8%, and accuracy was 96.8% (p < 0.001). Fractures were diagnosed in
      74.4% of the patients (24 of 31). Fourteen (43.2%) patients demonstrated non
      therapeutic laparotomy, in which minor lesions could have been managed
      conservatively. We concluded that MDCT is an accurate imaging method in
      evaluating selected AGWV, providing trusted information for emergency room
      physicians.

PMID- 22134844
TI  - Cognitive dysfunction and antiphospholipid antibodies.
AB  - Antiphospholipid syndrome (APS) is a multisystem prothrombotic condition,
      however, in recent years, its inflammatory nature has been studied extensively.
      Cerebral involvement is commonly observed in APS and results in different
      clinical manifestations. However, most of the studies include secondary APS. In
      this article, we review the prevalence, clinical characteristics, and
      physiopathology of cognitive impairment in patients with primary APS.

PMID- 22134845
TI  - Laboratory diagnosis of the lupus anticoagulant.
AB  - Lupus anticoagulants are autoantibodies that are associated with an increased
      risk of thromboembolic events and adverse pregnancy outcomes. They are identified
      by a systematic, laboratory-based approach that includes the following steps: 1)
      prolongation of a phospholipid-dependent screening assay, 2) demonstration of an
      inhibitory activity by mixing studies with healthy pooled plasma, and 3)
      documentation that the inhibitory activity is phospholipid dependent. Laboratory
      testing can be complicated by several variables, however, including preanalytical
      factors, multiple reagents and testing platforms, and difficulties with
      interpreting the results. Guidelines have been developed through several
      professional organizations that build upon the steps listed above and provide
      guidance to improve the reproducibility of test results. This article reviews the
      guidelines developed by the Lupus Anticoagulant/Phospholipid Dependent Antibodies
      Scientific and Standardization Committee of the International Society on
      Thrombosis and Haemostasis and addresses several common issues encountered during
      testing for these clinically relevant autoantibodies.

PMID- 22134846
TI  - Variable flip angle schedules in bSSFP imaging of hyperpolarized noble gases.
AB  - Balanced steady-state free precession imaging sequences provide signal-to-noise
      ratio benefits for MRI of hyperpolarized nuclei. Hyperpolarized magnetization
      decays during the imaging sequence to thermal equilibrium, effectively
      necessitating imaging in a transient state characterized by nonconstant
      transverse magnetization and k-space filtering when using constant flip angles.
      This work presents an analytical method for calculation of variable flip angle
      schedules which maintain constant transverse magnetization in balanced steady
      state free precession imaging of hyperpolarized nuclei. The approach is based on
      direct inversion of the Bloch equations and does not require any numerical
      optimization. Input parameters are pulse sequence timings and effective
      relaxation times, which take diffusion of hyperpolarized gas in imaging gradients
      into account. Provision of constant transverse magnetization is demonstrated in
      phantom experiments and human lung imaging using hyperpolarized (3) He. The
      benefit of a flat k-space filter is demonstrated by reduced blurring in (3) He
      and digital phantom data, and high quality (3) He ventilation images from human
      lungs are obtained.

PMID- 22134847
TI  - SPM43.1 contributes to acid-resistance of non-symplasmata-forming cells in
      Pantoea agglomerans YS19.
AB  - Pantoea agglomerans YS19 is a rice endophytic bacterium characterized to form
      multicellular biofilm-like structures called symplasmata. Phenotypic distinctions
      between symplasmata-forming cells and planktonic cells are crucial for
      understanding YS19's survival strategies. In this study, a 43.1 kDa protein
      SPM43.1 was identified to show significant resistance to the aggregation effect
      caused by denaturing acidic conditions. MALDI-TOF analysis data indicated that it
      is a maltose-binding protein homolog while contains sequence homologous to the
      chaperone protein, ClpB. The purified SPM43.1 protein was detected to exhibit
      chaperone-like activities at acidic conditions, where its conformation
      transformed from an ordered to a globally less ordered structure as revealed by
      circular dichroism spectroscopy, showing a similar property to most chaperone
      proteins. The expression of SPM43.1 in YS19 is initiated when bacterial cells
      begin to aggregate, yet its amount in planktonic cells greatly exceeds that in
      symplasmata-forming cells, suggesting its crucial role to the survival of
      planktonic cells in experiencing environmental fluctuations. However, the
      bacterium prefers to form symplasmata, while not to express SPM43.1 proteins, for
      surviving the artificially set fluctuant (acid here) environments. This study
      provides valuable information on the life styles and survival strategies of
      microorganisms that forms multicellular aggregates at specific growth stages.

PMID- 22134848
TI  - Phragmalin limonoids from Chukrasia tabularis var. velutina.
AB  - Two new C-15-acyl phragmalin limonoids, velutinalides A and B, featuring a C-16/C
      30 delta-lactone ring, and a new structurally related natural product, R310B8,
      were isolated from the leaves of Chukrasia tabularis var. velutina. Their
      structures were elucidated on the basis of extensive spectroscopic data analyses
      and by comparison of their NMR data with those of related known compounds.

PMID- 22134849
TI  - Inhibitory activity of alpha-amylase and alpha-glucosidase by plant extracts from
      the Brazilian cerrado.
AB  - Diabetes mellitus is the most common disease in the world. One therapeutic
      approach for treating diabetes is inhibition of alpha-amylase and alpha
      glucosidase activities to reduce postprandial blood glucose levels. In vitro
      tests showed that several plant extracts from Brazilian cerrado species can
      inhibit the activity of alpha-amylase and alpha-glucosidase. The extracts of
      Eugenia dysenterica, Stryphnodendron adstringens, Pouteria caimito, Pouteria
      ramiflora, and Pouteria torta showed strong alpha-amylase and alpha-glucosidase
      inhibitory activity. Eugenia dysenterica, P. caimito, P. ramiflora, and P. torta
      aqueous extracts exerted the highest activity against alpha-amylase (IC50) values
      of 14.93, 13.6, 7.08, and 5.67 ug/mL, respectively) and alpha-glucosidase (IC50
      values of 0.46, 2.58, 0.35, and 0.22 ug/mL, respectively). Stryphnodendron
      adstringens ethanol extract also exhibited inhibitory activity against both
      enzymes (IC50) 1.86 ug/mL against alpha-amylase and 0.61 ug/mL against alpha
      glucosidase). The results suggest that the activity of these cerrado plants on
      alpha-amylase and alpha-glucosidase represents a potential tool for development
      of new strategies for treatment of diabetes.

PMID- 22134850
TI  - Clustered organization, polycistronic transcription, and evolution of
      modification-guide snoRNA genes in Euglena gracilis.
AB  - Previous studies have shown that the eukaryotic microbe Euglena gracilis contains
      an unusually large assortment of small nucleolar RNAs (snoRNAs) and ribosomal RNA
      (rRNA) modification sites. However, little is known about the evolutionary
      mechanisms contributing to this situation. In this study, we have examined the
      organization and evolution of snoRNA genes in Euglena with the additional
      objective of determining how these properties relate to the rRNA modification
      pattern in this protist. We have identified and extensively characterized a
      clustered pattern of genes encoding previously biochemically isolated snoRNA
      sequences in E. gracilis. We show that polycistronic transcription is a prevalent
      snoRNA gene expression strategy in this organism. Further, we have identified 121
      new snoRNA coding regions through sequence analysis of these clusters. We have
      identified an E. gracilis U14 snoRNA homolog clustered with modification-guide
      snoRNA genes. The U14 snoRNAs in other eukaryotic organisms examined to date
      typically contain both a modification and a processing domain. E. gracilis U14
      lacks the modification domain but retains the processing domain. Our analysis of
      U14 structure and evolution in Euglena and other eukaryotes allows us to propose
      a model for its evolution and suggest its processing role may be its more
      important function, explaining its conservation in many eukaryotes. The
      preponderance of apparent small and larger-scale duplication events in the
      genomic regions we have characterized in Euglena provides a mechanism for the
      generation of the unusually diverse collection and abundance of snoRNAs and
      modified rRNA sites. Our findings provide the framework for more extensive whole
      genome analysis to elucidate whether these snoRNA gene clusters are spread across
      multiple chromosomes and/or form dense "arrays" at a limited number of
      chromosomal loci.

PMID- 22134852
TI  - A case study of measles vaccination for university students during the measles
      outbreak in Tokyo, Japan, 2007.
AB  - In April 2007, seven students belonging to the same class at Teikyo University
      developed measles. To prevent the spread of infection, 27 of 106 students in the
      same class who had low anti-measles antibody titers as measured by
      hemagglutination inhibition (HI) assay were vaccinated. After the outbreak had
      subsided, the HI values were investigated in 103 students, and they answered
      questionnaires about their health condition during the period of the outbreak and
      their previous clinical histories of measles, including vaccination records.
      There was no new case of measles after introduction of the vaccination program.
      However, the HI titers of 42% of the students who were not vaccinated in this
      program were significantly elevated. Fever and catarrhal signs occurred in 7 of
      these students with pre-exposure titers of 8 or less. The post-exposure HI titers
      of 71% of students who were unaffected by measles and had high HI titers (>8)
      before the epidemic did not increase. These results suggested that people with
      low HI titers may become potential carriers of measles and that measurement of
      pre-exposure HI anti-measles antibody titer is a useful method for selection of
      candidates to undergo vaccination.

PMID- 22134851
TI  - Clinical and polysomnographic data of positional sleep apnea and its predictors.
AB  - INTRODUCTION: In Asian population, facial structure may contribute to the primary
      pathophysiology of obstructive sleep apnea (OSA). We hypothesized that sleep
      position may have more effect on OSA in Asians compared to the Western
      population. If this hypothesis is accurate, positional therapy will have a major
      impact on treatment of OSA among Asians. PATIENTS/METHODS: We reviewed 263
      polysomnographic studies from our laboratory from January 1, 2010 to June 30,
      2010. Criteria for positional and non-positional OSA were (1) supine respiratory
      disturbance index (RDI)/non-supine RDI >=2 and total RDI >=5 and (2) supine
      RDI/non-supine RDI <2 and total RDI >=5, respectively. We aimed to determine the
      difference in baseline characteristics, polysomnographic findings, and predictors
      for positional OSA. RESULTS: We found 144 patients diagnosed with OSA (RDI >=5),
      and 96 patients met the criteria for positional OSA (67%), in which in almost
      half of these patients (47%), RDI was normalized (RDI < 5) in non-supine
      position. Snoring frequency were significantly lower among positional OSA and OSA
      was less severe indicated by lower RDI and arousal index, higher mean and nadir
      oxygen saturation, and higher %NREM3. We also found that low snoring frequency
      (less than 20% of total sleep time) was a significant predictor for positional
      OSA (odd ratio of 3.27; p = 0.011), contrarily to low mean oxygen saturation
      (<95%) which was found to be a negative predictor (odd ratio of 0.31; p = 0.009).
      Among OSA patients, low RDI (<15) was a significant predictor for normalization
      of RDI in non-supine position (odd ratio of 8.77; p = < 0.001), contrarily to low
      mean oxygen saturation (<95%) which was also found to be a negative predictor
      (odd ratio of 0.13; p = 0.001). CONCLUSION: Positional OSA is very prevalent and
      noted in almost 70% of our patients. Low snoring frequency was noted to be a
      positive predictor for positional OSA, contrarily to low mean oxygen saturation
      which was found to be a negative predictor. These findings are encouraging that
      positional therapy can be very beneficial as the treatment modality for OSA among
      Asians.

PMID- 22134853
TI  - Treatment of patients with left main coronary artery disease.
AB  - OPINION STATEMENT: Considering lesion priority and its clinical consequences,
      coronary artery bypass grafting (CABG) has been a treatment of choice for
      revascularization in patients with significant left main coronary artery (LMCA)
      disease, However, with remarkable advancements in techniques of percutaneous
      coronary intervention (PCI), supporting devices, and adjunctive pharmacologic
      therapy, PCI with stenting has emerged to be a less invasive and feasible
      revascularization treatment for these patients. The cumulative evidence suggests
      that the safety outcomes such as mortality or composite of death, myocardial
      infarction, and stroke are similar among PCI and CABG, with the only difference
      being the rate of repeat revascularization. Based on these data, the current
      guideline of revascularization of LMCA disease has adopted an increasing off
      label experience with stenting and clinical studies and been updated to partly
      approve PCI as a viable alternative (in level of class IIb) in selected patients.
      The choice of PCI or CABG for unprotected LMCA disease depends on several
      clinical and anatomic features, ensuring crucial patient selection to be a
      cornerstone for achieving favorable long-term outcomes. In patients with very
      complex anatomic features and concomitant diffuse multivessel disease, CABG is
      preferred so as to avoid procedural and future thrombotic risks and to provide
      more complete revascularization. By contrast, in patients with relatively simple
      LMCA disease, such as ostial/shaft LMCA disease, isolated LMCA disease (with or
      without one or two-vessel involvement), and LMCA disease with low SYNTAX score,
      PCI is an alternative, and in some cases a preferred, strategy to reduce surgical
      risks (eg, stroke and in-hospital events following major surgery). For the
      future, ongoing large clinical trials might also boost interventional
      cardiologists to select PCI with stenting as an alternative revascularization
      strategy for unprotected LMCA disease. This evidence will most likely change the
      current clinical practice and guidelines of optimal revascularization strategy
      for unprotected LMCA disease.

PMID- 22134854
TI  - Characteristic, composition, and sources of TSP investigated by HRTEM/EDS and
      ESEM/EDS.
AB  - Total suspended particle (TSP) collected at the fifth floor of House Dust in
      Hunan University, China, was analyzed in terms of microscopic morphology and
      chemical composition. The fine particles (50 nm-2 MUm) in the TSP were analyzed
      by a high-resolution transmission electron microscope equipped with an energy
      dispersive X-ray analyzer (HRTEM/EDS). Results showed that the particles were in
      shapes of plate, irregular and agglomerate. Based on EDS results, these fine
      particulate matter was primarily composed of Fe-rich (35.82-61.29%), Ca-rich
      (30.18-36.77%) and Si-rich (18.95-32.28%) particles. Other elements mainly
      including Mg (0.47-4.97%), Al (0.45-14.57%), S (0.45-4.73%), K (1.13-2.13%) and
      Zn (0.67-3.85%) were also observed. The sources analysis indicated that the HRTEM
      particles mainly originated from coal combustion, traffic emission, vehicles
      exhaust emission and fugitive soil or cement particulate matter. The coarse
      particles (4-50 MUm) were detected by environmental scanning electron microscopy
      coupled with energy-dispersive X-ray detector (ESEM/EDS). Based on a simple
      algorithm, ESEM particles were categorized into five groups: C-bearing (46.15%,
      67% and 86.98%), Si + Ca-bearing (21.48 + 11.80%, 16.51 + 10.81% and 16.32 +
      10.62%), Si + Al-bearing (20.06 + 12.40%, 20.16 + 11.22% and 15.31 + 11.25%), Si
      bearing (34.40%, 26.92% and 27.15%) particles and aggregates, most of which
      exhibit obvious crystalline structure, and these ESEM particles mainly derived
      from vehicles exhaust emission, coal combustion, soil, and biomass burning, while
      the aggregates are indicative of atmospheric reaction progress. HRTEM/EDS and
      ESEM/EDS are mutual complementary in analyzing the characteristic and determining
      the sources of TSP.

PMID- 22134855
TI  - Deformation of slopes as a cause of underground mining activities: three case
      studies from Ostrava-Karvina coal field (Czech Republic).
AB  - Underground mining activities may potentially play a role on the initiation and
      reactivation of the slope movements. However, an adequate attention has not yet
      been paid to these problems; in this study, the possible influence of present and
      former mining activities on the selected set of model slope deformations in the
      Ostrava-Karvina Coalfield (Opliji, Repiste and Orlova Lazy District) was analysed
      and a methodology for their observation for application to similar conditions and
      influence was described. Isocatabase maps, terrain deformation parameters
      calculated for the point lying on the slope deformation surface, length
      measurement by zone extensometer and dilatometer measurement in cracks was also
      provided for evaluation of the underground mining impact. It was found that
      inclinations of both boreholes were evidence of underground mining impact, and
      localization of inclinometer measurement on boreholes in the active part as well
      as in the near vicinity was very important as an important result of this study.
      Analysis of underground mining activity influence on model localities in relation
      to performed mining operations, subsidence and other influences on the ground
      surface was also determined. Thus, the study will contribute to a more objective
      knowledge of these problems of interest for the professional public and also for
      the state administration to solve problems associated with the utilisation and
      settlement of such affected areas.

PMID- 22134856
TI  - Occurrence and fate of steroid estrogens in the largest wastewater treatment
      plant in Beijing, China.
AB  - Concern over steroid estrogens has increased rapidly in recent years due to their
      adverse health effects. Effluent discharge from wastewater treatment plants
      (WWTPs) is the main pollutant source for environmental water. To understand the
      pollutant level and fate of steroid estrogens in WWTPs, the occurrence of estrone
      (E1), 17-beta-estradiol (E2), estriol (E3), and 17-beta-ethinylestradiol (EE2)
      was investigated in the Gaobeidian WWTP in Beijing, China. Water samples from
      influent as well as effluent from second sedimentation tanks and advanced
      treatment processes were taken monthly during 2006 to 2007. In influent, steroid
      estrogen concentrations varied from 11.6 to 1.1 * 10(2) ng/l, 3.7 to 1.4 * 10(2)
      ng/l, no detection (nd) to 7.6*10(2) ng/l and nd to 3.3 * 10(2) ng/l for E1, E2,
      E3, and EE2, respectively. Compared with documented values, the higher steroid
      estrogen concentrations in the WWTP influent may be due to higher population
      density, higher birthrate, less dilution, and different sampling time. Results
      revealed that a municipal WWTP with an activated sludge system incorporating
      anaerobic, anoxic, and aerobic processes could eliminate natural and synthetic
      estrogens effectively. The mean elimination efficiencies were 83.2%, 96.4%,
      98.8%, and 93.0% for E1, E2, E3, and EE2, respectively. The major removal
      mechanism for natural estrogens and synthetic estrogen EE2 were biodegradation
      and sorption on the basis of mass balance in water, suspension particles, and
      sludge. In the WWTP effluent, however, the highest concentrations of E1, E2, E3,
      and EE2 attained were 74.2, 3.9, 5.1, and 4.6 ng/l, respectively. This is
      concerning as residual steroid estrogens in WWTP effluent could lead to pollution
      of the receiving water. Advanced flocculation treatment was applied in the WWTP
      and transformed the residual estrogen conjugates to free species, which were
      reduced further by filtration with removal shifting from 32% to 57% for natural
      estrogen, although no EE2 was removed.

PMID- 22134857
TI  - Characterizing ecological risk for polycyclic aromatic hydrocarbons in water from
      Lake Taihu, China.
AB  - Lake Taihu provides vital ecological services for humans in China; it receives a
      great deal of attention regarding its ecological and environmental conditions. In
      this study, the ecological risks of eight individual polycyclic aromatic
      hydrocarbons (PAHs) in water were assessed using probabilistic distributions of
      the hazard quotient based on Monte Carlo simulation. The results show that the
      95th percentile of the hazard quotients ranged from 0.00074 to 2.831, and the
      ecological risk of Flua was highest, followed by, in descending order of risk,
      B[a]P > Pyr > Ant > Phe > Flu > Ace > Chr. The probabilities of hazard quotients
      exceeding a decision criteria of 0.3 were 18.09%, 6.51%, 3.76%, and 2.85% for
      Flua, B[a]P, Pyr, and Ant, respectively, indicating their potential ecological
      risks to aquatic organisms. The spatial distribution of hazard quotients for
      these four individual PAHs with potential ecological risk were obtained using
      Geographic Information System (GIS), and similar spatial distribution patterns
      were also observed in the lake. The highest ecological risks of these four
      individual PAHs to aquatic organisms were found in Meiliang Bay, followed by
      Gonghu Bay and Xukou Bay. The uncertainty within the ecological risk assessment
      was also discussed.

PMID- 22134858
TI  - A review on human attitudes towards reptiles in Brazil.
AB  - For many millennia humans and reptiles have interacted, but the attitude of
      humans towards these animals has depended on culture, environment, and personal
      experience. At least 719 reptile species are known to occur in Brazil and about
      11% of this fauna has been exploited for many different purposes, including
      bushmeat, leather, ornamental and magic/religious uses, and as folk medicines.
      Brazil can therefore serve as an interesting case study for better understanding
      reptile use by human societies, and the present paper catalogues some of the
      reptile species being used in Brazil and discusses implications for their
      conservation. A literature review indicated that 81 reptile species are
      culturally important in this country, with 47 (58%) species having multiple uses,
      54 being used for medicinal purposes, 38 as food, 28 for ornamental or decorative
      purposes, 20 used in magic/religious practices, 18 as pets, and 40 are commonly
      killed when they come into contact with humans. Regarding their conservation
      status, 30 (37.5%) are included on State's Red List, Brazilian Red List or the
      IUCN Red List. There are many forms of interaction between reptiles and humans in
      Brazil-although most of them are quite negative in terms of wildlife conservation
      which reinforces the importance of understanding such uses and interactions in
      the context of protecting reptiles in Brazil. A better understanding of the
      cultural, social, and traditional roles of these reptiles is fundamental to
      establishing management plans for their sustainable use.

PMID- 22134859
TI  - Mathematical requirements of visual-vestibular integration.
AB  - This article addresses the intersection between perceptual estimates of head
      motion based on purely vestibular and purely visual sensation, by considering how
      nonvisual (e.g. vestibular and proprioceptive) sensory signals for head and eye
      motion can be combined with visual signals available from a single landmark to
      generate a complete perception of self-motion. In order to do this, mathematical
      dimensions of sensory signals and perceptual parameterizations of self-motion are
      evaluated, and equations for the sensory-to-perceptual transition are derived.
      With constant velocity translation and vision of a single point, it is shown that
      visual sensation allows only for the externalization, to the frame of reference
      given by the landmark, of an inertial self-motion estimate from nonvisual
      signals. However, it is also shown that, with nonzero translational acceleration,
      use of simple visual signals provides a biologically plausible strategy for
      integration of inertial acceleration sensation, to recover translational
      velocity. A dimension argument proves similar results for horizontal flow of any
      number of discrete visible points. The results provide insight into the
      convergence of visual and vestibular sensory signals for self-motion and indicate
      perceptual algorithms by which primitive visual and vestibular signals may be
      integrated for self-motion perception.

PMID- 22134860
TI  - Adsorption of Remazol Red 198 onto magnetic N-lauryl chitosan particles:
      equilibrium, kinetics, reuse and factorial design.
AB  - PURPOSE: The discharge of colored effluents from industries is an important
      environmental issue and it is indispensable to remove the dyes before the water
      gets back to the rivers. The magnetic adsorbents present the advantage of being
      easily separated from the aqueous system after adsorption by positioning an
      external magnetic field. METHODS: Magnetic N-lauryl chitosan (L-Cht/gamma
      Fe(2)O(3)) particles were prepared and characterized by Fourier transform
      infrared spectroscopy, thermogravimetric analysis, transmission electron
      microscopy, and vibrating sample magnetometry. Remazol Red 198 (RR198) was used
      as a reactive dye model for adsorption on L-Cht/gamma-Fe(2)O(3). The adsorption
      isotherms were performed at 25 degrees C, 35 degrees C, 45 degrees C, and 55
      degrees C and the process was optimized using a 2(3) factorial design (analyzed
      factors: pH, ionic strength, and temperature). The desorption and regeneration
      studies were performed in a three times cycle. RESULTS: The characterization of
      the material indicated that the magnetic particles were introduced into the
      polymeric matrix. The pseudo-second order was the best model for explaining the
      kinetics and the Langmuir-Freundlich was the best-fitted isotherm model. At room
      temperature, the maximum adsorption capacity was 267 mg g(-1). The material can
      be reused, but with a decrease in the amount of adsorbed dye. CONCLUSIONS: L
      Cht/gamma-Fe(2)O(3) is a promising material to remove RR198 and probably other
      similar reactive dyes from aqueous effluents.

PMID- 22134861
TI  - Effects of alfalfa and organic fertilizer on benzo[a]pyrene dissipation in an
      aged contaminated soil.
AB  - BACKGROUND: A climate-controlled pot experiment was conducted to investigate the
      effects of planting alfalfa and applying organic fertilizer on the dissipation of
      benzo[a]pyrene from an aged contaminated agricultural soil. RESULTS: Short-term
      planting of alfalfa inhibited the dissipation of benzo[a]pyrene from the soil by
      8.9%, and organic fertilizer enhanced benzo[a]pyrene removal from the soil by
      11.6% compared with the unplanted and unfertilized treatments, respectively. No
      significant interaction was observed between alfalfa and organic fertilizer on
      benzo[a]pyrene dissipation. Sterilization completely inhibited the removal of
      benzo[a]pyrene from the soil indicating that its degradation by indigenous
      microorganisms may have been the main mechanism of dissipation. Furthermore,
      significant positive relationships were observed between benzo[a]pyrene removal
      and the contents of soil ammonium nitrogen, nitrate nitrogen, and total mineral
      nitrogen at the end of the experiment, suggesting that competition between plants
      and microorganisms for nitrogen may have inhibited benzo[a]pyrene dissipation in
      the rhizosphere of alfalfa and the addition of organic fertilizer may facilitate
      microbial degradation of benzo[a]pyrene in the soil.

PMID- 22134862
TI  - Mycoremediation--a prospective environmental friendly technique of bioseparation
      and dewatering of domestic wastewater sludge.
AB  - INTRODUCTION: Environmental safe and friendly management and disposal of
      wastewater sludge is a problem of every treatment plant throughout the world.
      Bioseparation and dewaterability of raw domestic wastewater sludge were evaluated
      for proper management and disposal by mycoremediation, i.e., using prior grown 2%
      (v/v) spore suspension of filamentous fungal (Mucor hiemalis Wehmer) broth
      inoculation, which were grown in 2% (w/v) solution of malt extract and wheat
      flour for 48-60 h in orbital shaker. DISCUSSION: Within 2-3 days of treatment
      application, encouraging results were achieved in total dry solids (TDS), total
      suspended solid (TSS), turbidity, chemical oxygen demand (COD), specific
      resistance to filtration (SRF), and pH due to fungal treatment in recognition of
      bioseparation and dewaterability of wastewater sludge compared to control. The
      significant reduction of TDS was remarked at fungal biomass (FB) in wheat flour
      (WF) treatment. The removal of TSS, turbidity, COD, and SRF were observed 96.0%,
      99.4%, 92.6%, and 97.6%, respectively, in supernatant at 5 days by FB in WF. The
      SRF measuring the dewaterability was decreased with maximum (0.26 * 10(-12)
      mg/kg) equivalent to 95.5% at 2 days in FB in WF also. FB in WF broth is a
      potential, environmental friendly, comparatively low-cost biological technique
      which might play the significant role for bioremediation and bioseparation of
      domestic wastewater sludge. The present technique may bring a dynamic change in
      treatment of wastewater in future.

PMID- 22134863
TI  - Concurrent effects of resource pulse amount, type, and frequency on community and
      population properties of consumers in detritus-based systems.
AB  - Episodic resource inputs (i.e., pulses) can affect food web properties and
      community dynamics, but detailed mechanistic understanding of such effects remain
      elusive. Natural aquatic microsystems (e.g., tree holes, human-made containers)
      are colonized by invertebrates that form complex food webs dependent on episodic
      and sometimes sizeable inputs of allochthonous detritus from adjacent terrestrial
      environments. We investigated how variation in pulse frequency, amount, and
      resource type interacted to affect richness, abundance, composition, and
      population sizes of colonizing invertebrates in water-filled tires and tree hole
      analogs in a forest habitat. Different container types were used to assess the
      generality of effects across two environmental contexts. Containers received
      large infrequent or small frequent pulses of animal or leaf detritus of different
      cumulative amounts distributed over the same period. Invertebrates were sampled
      in June and September when cumulative detritus input was equal for the two pulse
      frequencies. Pulse frequency and detritus type interacted to affect the responses
      of richness and abundance in both months; pulse frequency alone in June affected
      the relationship between richness and abundance. Richness and abundance were also
      greater with more detritus regardless of detritus type. One group, the filter
      feeders, were most important in driving the response of abundance and richness to
      pulses, especially in June. This work highlights the potential complex nature of
      responses of communities and populations to resource pulses and implicates the
      ability of certain groups to exploit pulses of detrital resources as a key to
      understanding community-level responses to pulses.

PMID- 22134864
TI  - [Developments in neurological rehabilitation].

PMID- 22134865
TI  - [DGRW-update: neurology--from empirical strategies towards evidence based
      interventions].
AB  - Stroke, Multiple Sclerosis (MS), traumatic brain injuries (TBI) and neuropathies
      are the most important diseases in neurological rehabilitation financed by the
      German Pension Insurance. The primary goal is vocational (re)integration. Driven
      by multiple findings of neuroscience research the traditional holistic approach
      with mainly empirically derived strategies was developed further and improved by
      new evidence-based interventions. This process had been, and continues to be,
      necessary to meet the health-economic pressures for ever shorter and more
      efficient rehab measures. Evidence-based interventions refer to symptom-oriented
      measures, to team-management concepts, as well as to education and psychosocial
      interventions. Drug therapy and/or neurophysiological measures can be added to
      increase neuroregeneration and neuroplasticity. Evidence-based aftercare concepts
      support sustainability and steadiness of rehab results.Mirror therapy, robot
      assisted training, mental training, task-specific training, and above all
      constraint-induced movement therapy (CIMT) can restore motor arm and hand
      functions. Treadmill training and robot-assisted training improve stance and
      gait. Botulinum toxine injections in combination with physical and redressing
      methods are superior in managing spasticity. Guideline-oriented management of
      associated pain syndromes (myofascial, neuropathic, complex-regional=dystrophic)
      improve primary outcome and quality of life. Drug therapy with so-called co
      analgetics and physical therapy play an important role in pain management.
      Swallowing disorders lead to higher mortality and morbidity in the acute phase;
      stepwise diagnostics (screening, endoscopy, radiology) and specific swallowing
      therapy can reduce these risks and frequently can restore normal eating und
      drinking.In our modern industrial societies communicative and cognitive
      disturbances are more impairing than the above mentioned disorders. Speech and
      language therapy (SLT) is dominant in communicative disorders; the therapists use
      communicative and/or linguistics-oriented strategies. SLT must begin early after
      disease onset and with high frequency to elicit good results. PC-assisted (self
      )training, possibly telemedically applied, can increase training frequency and
      time and, hence, improve outcome in aphasia. High-frequency and task-specific
      training, often PC-assisted, were found to be relevant for improving cognitive
      functions in all dimensions. Several strategies seem to be efficient in neglect.
      Visual field deficits can be treated restitutively and compensatingly by PC
      assisted training. Attention, memory and executive dysfunctions each require
      multimodal specific treatment strategies, performed in single and group therapy
      and in PC-assisted training. Also, education of patients to cope with their
      impairments and disabilities is another important part. Combined medically and
      vocationally oriented rehabilitation settings are necessary for raising the rate
      of return-to-work, especially in patients with motor hand impairments or
      cognitive disorders. Education of patients and relatives to cope with the chronic
      neurological diseases and disablements highly improve the sustainability of rehab
      results and can, in the long run, also reduce mortality and admission to nursing
      homes. Appropriate physical activity and sports are relevant in the phase of
      aftercare, by stabilizing both motor coordination and cognitive factors; in MS
      patients fatigue can be diminished effectively.The main mental comorbidities are
      anxiety and depression. Pharmacological and psychological treatments have been
      found to be equally important in this context. Frequently, these mental disorders
      appear in the phase of aftercare and long-term course only, then worsening
      outcome sustainability. Efficient concepts to deal with this aspect are still
      missing. The ambulatory health care system can not cope with it until now.The
      multitude of evidence-based interventions have over the last 20 years after the
      Rehab Commission of the Federation of the German Pension Insurance Institutes
      contributed decisively to even improving primary outcomes and quality of life of
      neurological patients in spite of shortened length of stay and other
      restrictions. Neurorehabilitative research, especially the clinically oriented
      part, had a major influence on the process of professionalization of all members
      in the neurorehabilitative team. This fact enables new and more efficient
      organizational structures and working processes within the team; the discussion
      on this topic has however only just started.

PMID- 22134866
TI  - [Disease-related self-management of obese children and children with bronchial
      asthma: changes and predictors during inpatient rehabilitation].
AB  - BACKGROUND AND SIGNIFICANCE: There is growing interest in disease-related self
      management as a means of coping with chronic disease. Improving disease-related
      self-management has thus become a key aim of inpatient medical rehabilitation of
      children and adolescents. We conducted this study in the framework of the project
      entitled "Outcome quality in medical inpatient rehabilitation of children and
      adolescents" initiated and financed by the German statutory pension and statutory
      health insurance programmes. STUDY AIM: Our study aim was to examine any changes
      following inpatient medical rehabilitation in the diagnosis-specific disease self
      management of children suffering from obesity and from bronchial asthma. In
      addition we sought to identify any personal characteristics of the rehabilitants
      that might predict changes in self-management. METHODS: We collected data from 17
      inpatient medical rehabilitation centres on disease-related self-management in
      children with obesity (n=706) and bronchial asthma (n=162) at the start of
      rehabilitation and 6 weeks after rehabilitation. The age of the diagnostic group
      "obesity" averaged 14.3 years, with a male percentage of 39.3%. The average age
      in the diagnostic group "bronchial asthma" was 14.0 years, with a male percentage
      of 54.2%. A questionnaire was used addressing the self-management of chronically
      ill young people. To compare the results from both measurement occasions, we
      employed t-tests for dependent samples and calculated effect-sizes. Using
      hierarchical regression analyses, we determined predictors of change in disease
      related self-management. The predictor variables were included into the
      hierarchical regression analyses within 6 topical blocks (baseline disease
      management, sociodemography, body functions, baseline quality of life, motivation
      for rehabilitation, and duration of rehabilitation). RESULTS: We observed
      significant post-rehabilitation improvement of disease-related self-management in
      both the obese (T=-22.423; p<0.001) and the bronchial asthma group (T=-5.349;
      p<0.001). This improvement revealed a strong effect in the obese group (SRM=0.84)
      and a moderate effect in the bronchial asthma group (SRM=0.42). Regression
      analyses explained 3.4% of the variance in the obese group and 31.3% in the
      bronchial asthma group. In the latter group, self-management 6 weeks after the
      end of rehabilitation can be predicted by good self-management at the start of
      rehabilitation (beta=0.516; p<0.001) as well as primary school attendance
      (beta=0.201; p<0.01). DISCUSSION: Our results show that the disease-related self
      management of obese youngsters and those with bronchial asthma benefits from
      inpatient rehabilitation. Changes in self-management are only poorly predicted by
      the variables included in the regression analysis in the diagnostic group
      "obesity". Other factors than those considered in this study seem to influence
      the success of treatment. In the diagnostic group "bronchial asthma" a
      significantly higher proportion of incremental variance can be explained, the
      extent of disease management at the beginning of rehabilitation being the most
      important predictor.

PMID- 22134867
TI  - ["Sustainability through Networking"--20th Rehabilitation Science Colloquium
      March 14-16, 2011 in Bochum].

PMID- 22134869
TI  - An orthogonal-based decoupling method for MRI phased array coil design.
AB  - A new 2 T 3-element orthogonal knee coil array based on the three-dimensional
      orthogonality principle was designed, constructed and used in a series of pilot
      magnetic resonance imaging (MRI) studies on a standardized phantom, and human and
      pig knees. The coil elements within this new coil array are positioned orthogonal
      to one another allowing problematic mutual coupling effects to be minimized
      without the use of any passive mutual decoupling schemes. The proposed method is
      appropriate for the design of transmit, receive and/or transceive radiofrequency
      (RF) coil arrays for applications in animal/human MRI and spectroscopic studies.
      Experimental results demonstrated that the 3-element orthogonal knee coil array
      could be angled arbitrarily, including at 90 degrees , relative to the main
      static magnetic field (B(0) ) whilst maintaining normal operation with minimal
      loss of efficiency and functionality. Initial trials with a pig knee specimen
      further showed that the greatest signal intensity in the patellar ligament
      (parallel collagen fibres) was observed when the orthogonal knee coil array and
      the pig knee specimen were angled at ~55 degrees  to B(0) , which may have
      potential uses in magic angle MR applications.

PMID- 22134870
TI  - Involvement of glomerular renin-angiotensin system (RAS) activation in the
      development and progression of glomerular injury.
AB  - Recently, there has been a paradigm shift away from an emphasis on the role of
      the endocrine (circulating) renin-angiotensin system (RAS) in the regulation of
      the sodium and extracellular fluid balance, blood pressure, and the
      pathophysiology of hypertensive organ damage toward a focus on the role of tissue
      RAS found in many organs, including kidney. A tissue RAS implies that RAS
      components necessary for the production of angiotensin II (Ang II) reside within
      the tissue and its production is regulated within the tissue, independent of the
      circulating RAS. Locally produced Ang II plays a role in many physiological and
      pathophysiological processes such as hypertension, inflammation, oxidative
      stress, and tissue fibrosis. Both glomerular and tubular compartments of the
      kidney have the characteristics of a tissue RAS. The purpose of this article is
      to review the recent advances in tissue RAS research with a particular focus on
      the role of the glomerular RAS in the progression of renal disease.

PMID- 22134871
TI  - Activated macrophages containing tumor marker in colon carcinoma:
      immunohistochemical proof of a concept.
AB  - The presence of carcinoembryonic antigen (CEA)-containing activated macrophages
      has been demonstrated in peripheral blood from patients with colorectal
      carcinoma. Macrophages migrate from the circulation into the tissue, phagocytose
      debris, and return to the bloodstream. Hence it seems likely that activated
      macrophages containing tumor debris, i.e., tumor marker, are present in the
      stroma of colorectal carcinoma. After phagocytosis, they could follow a
      hematogenic or lymphogenic route to the peripheral blood. The aim of this study
      is to assess the presence of tumor marker-containing activated macrophages in the
      stroma of colon carcinoma and in regional lymph nodes. From 10 cases of colon
      carcinoma, samples of tumor tissue and metastasis-free lymph nodes were cut in
      serial sections and stained for CD68 to identify macrophages and for CEA,
      cytokeratin, or M30 presence. Slides were digitalised and visually inspected
      using two monitors, comparing the CD68 stain to the tumor marker stain to
      evaluate the presence of tumor marker-positive macrophages. Macrophages
      containing tumor marker could be identified in tumor stroma and in metastasis
      free regional lymph nodes. The distribution varied for the different markers, CEA
      positive macrophages being most abundant. The presence of macrophages containing
      tumor marker in the tumor stroma and lymph nodes from patients with colon
      carcinoma could be confirmed in this series using serial immunohistochemistry.
      This finding supports the concept of activated macrophages, after phagocytosing
      cell debris, being transported or migrating through the lymphatic system. These
      results support the potential of tumor marker-containing macrophages to serve as
      a marker for diagnosis and follow-up of colon cancer patients.

PMID- 22134872
TI  - Cellular changes in the tumor microenvironment of human esophageal squamous cell
      carcinomas.
AB  - The growth, invasiveness, and metastasis of human cancers are not only determined
      by the cancer cells but also by their microenvironment. The purpose of this study
      was to extend our previous studies and to examine the cellular changes in tumor
      microenvironment (stroma) of esophageal squamous cell carcinomas (ESCCs). The
      proliferative activity, cellular components, and angiogenesis status in different
      compartments (non-tumor stroma, tumor stroma, and tumor periphery stroma) of
      ESCCs were evaluated by immunohistochemistry. The results revealed a
      hyperproliferative rate labeled by Ki-67 in stromal cells in tumor area as
      compared with that in stromal cells in non-tumor area, which resulted in the
      increased densities of myofibroblasts (labeled by smooth muscle actin (SMA)
      alpha), lymphocytes (labeled by CD3), macrophages (labeled by CD68), and the
      activation of angiogenesis characterized by increased microvessel density (MVD)
      and the increased expression of the proangiogenic factors (vascular endothelial
      growth factor and interleukin 8) in the tumor stroma. Further analysis showed
      that the changes of stromal cell density were more significant in the area of
      periphery tumor stroma than that of stroma between tumor nests. Most cellular
      changes were significantly associated with lymph node involvement. Double
      immunohistochemistries with PCNA/CD3, PCNA/CD68, and PCNA/SMA-alpha revealed that
      these cells present in the ESCC tumor stroma had a proliferative capacity. The
      cells present in the tumor microenvironment of ESCCs were greatly activated,
      suggesting that microenvironmental components may be involved in the cancer
      growth and progression.

PMID- 22134873
TI  - MMP-3 provokes CTGF/CCN2 production independently of protease activity and
      dependently on dynamin-related endocytosis, which contributes to human dental
      pulp cell migration.
AB  - Matrix metalloproteinase-3 (MMP-3) expression is promoted after pulpotomy, and
      application of MMP-3 to dental pulp after pulpotomy accelerates angiogenesis and
      hard tissue formation. However, the mechanism by which MMP-3 promotes dental pulp
      wound healing is still unclear. Connective tissue growth factor/CCN family 2
      (CTGF/CCN2), a protein belonging to the CCN family, is considered to participate
      in wound healing, angiogenesis, and cell migration. In this study, we examined
      the involvement of CTGF/CCN2 in MMP-3-induced cell migration in human dental pulp
      (fibroblast-like) cells. In human dental pulp cells, MMP-3 promoted cell
      migration, but this effect was clearly blocked in the presence of anti-CTGF/CCN2
      antibody. MMP-3 provoked mRNA and protein expression and secretion of CTGF/CCN2
      in a concentration- and time-dependent manner. The MMP-3 inhibitor NNGH failed to
      suppress MMP-3-induced CTGF/CCN2 protein expression. The potent dynamin inhibitor
      dynasore clearly inhibited MMP-3-induced CTGF/CCN2 expression. These results
      strongly suggest that MMP-3 induces CTGF/CCN2 production independently of the
      protease activity of MMP-3 and dependently on dynamin-related endocytosis, which
      is involved in cell migration in human dental pulp cells.

PMID- 22134874
TI  - Identification of a C2H2-type zinc finger transcription factor (ZAT10) from
      Arabidopsis as a substrate of MAP kinase.
AB  - Mitogen-activated protein kinases (MAPKs or MPKs) are one of the most important
      and conserved signaling molecules in plants. MPKs can directly modulate gene
      expression by the phosphorylation of transcription factors. However, only a few
      target substrates of MPKs have been isolated. Here, we identified a C(2)H(2)-type
      zinc finger transcription factor from Arabidopsis, ZAT10, as a substrate of MPKs.
      Using in vitro and in vivo protein-protein interaction analyses, we demonstrated
      that ZAT10 directly interacted with MPK3 and MPK6. ZAT10 was phosphorylated by
      recombinant Arabidopsis MPK3 and MPK6 in a kinase assay. Furthermore, ZAT10 was
      also phosphorylated by native MPK3 and MPK6 prepared from Arabidopsis plants in
      an in-gel kinase assay. Mass spectrometry analysis of phosphopeptides was used to
      determine two MPK phosphorylation sites in ZAT10. These sites were verified by
      site-directed mutagenesis and in vitro kinase assays.

PMID- 22134875
TI  - The physiology of ex vitro pineapple (Ananas comosus L. Merr. var MD-2) as CAM or
      C3 is regulated by the environmental conditions.
AB  - Many plant species grown under in vitro controlled conditions can be used as
      models for the study of physiological processes. Adult pineapple can display CAM
      physiology while in vitro it functions as a C3 plant. Ex vitro Ananas comosus has
      plastic morphology and physiology, both easy to modify from C3 to CAM by changing
      the environmental conditions. The yield of survival for a rentable propagation
      protocol of pineapple is closely related with the C3/CAM shift and the associated
      physiological characteristics. In the present work, ex vitro pineapple plants
      were divided in two sets and subjected to C3 and CAM-inducing environmental
      conditions, determined by light intensity and relative humidity, respectively, 40
      MUmol m(-2) s(-1)/85% and 260 MUmol m(-2) s(-1)/50%. The results demonstrated
      that the stress imposed by the environmental conditions switched pineapple plants
      from C3 to CAM behavior. Comparing to CAM induced, C3-induced pineapple plants
      showed substandard growth parameters and morphological leaf characteristics but a
      better rooting process and a higher ABA production, a phenotype closer to adult
      plants, which are expected to produce fruits in a normal production cycle. We
      conclude that the upholding of these characteristics is conditioned by low light
      intensity plus high relative humidity, especially during the first 8 weeks of ex
      vitro growth. It is expected that the better understanding of pineapple
      acclimatization will contribute to the design of a protocol to apply as a
      rentable tool in the pineapple agronomic industry.

PMID- 22134876
TI  - Bioprocessing of plant-derived virus-like particles of Norwalk virus capsid
      protein under current Good Manufacture Practice regulations.
AB  - Despite the success in expressing a variety of subunit vaccine proteins in plants
      and the recent stride in improving vaccine accumulation levels by transient
      expression systems, there is still no plant-derived vaccine that has been
      licensed for human use. The lack of commercial success of plant-made vaccines
      lies in several technical and regulatory barriers that remain to be overcome.
      These challenges include the lack of scalable downstream processing procedures,
      the uncertainty of regulatory compliance of production processes, and the lack of
      demonstration of plant-derived products that meet the required standards of
      regulatory agencies in identity, purity, potency and safety. In this study, we
      addressed these remaining challenges and successfully demonstrate the ability of
      using plants to produce a pharmaceutical grade Norwalk virus (NV) vaccine under
      current Good Manufacture Practice (cGMP) guidelines at multiple gram scales. Our
      results demonstrate that an efficient and scalable extraction and purification
      scheme can be established for processing virus-like particles (VLPs) of NV capsid
      protein (NVCP). We successfully operated the upstream and downstream NVCP
      production processes under cGMP regulations. Furthermore, plant-derived NVCP VLP
      demonstrates the identity, purity, potency and safety that meet the preset
      release specifications. This material is being tested in a Phase I human clinical
      trial. This research provides the first report of producing a plant-derived
      vaccine at scale under cGMP regulations in an academic setting and an important
      step for plant-produced vaccines to become a commercial reality.

PMID- 22134877
TI  - Insights into the Maya Blue technology: greenish pellets from the ancient city of
      La Blanca.

PMID- 22134878
TI  - Pathophysiology of microwave radiation: effect on rat brain.
AB  - The study aims to investigate the effect of 2.45 GHz microwave radiation on
      Wistar rats. Rats of 35 days old with 130 +/- 10 g body weight were selected for
      this study. Animals were divided into two groups: sham exposed and experimental
      (six animals each). Animals were exposed for 2 h a day for 45 days at 2.45 GHz
      frequency (power density, 0.21 mW/cm(2)). The whole body specific absorption rate
      was estimated to be 0.14 W/kg. Exposure took place in a ventilated plexiglas cage
      and kept in an anechoic chamber under a horn antenna. After completion of the
      exposure period, rats were killed, and pineal gland and whole brain tissues were
      isolated for the estimation of melatonin, creatine kinase, caspase 3, and calcium
      ion concentration. Experiments were performed in a blind manner and repeated. A
      significant decrease (P < 0.05) was recorded in the level of pineal melatonin of
      exposed group as compared with sham exposed. A significant increase (P < 0.05) in
      creatine kinase, caspase 3, and calcium ion concentration was observed in whole
      brain of exposed group of animals as compared to sham exposed. One-way analysis
      of variance method was adopted for statistical analysis. The study concludes that
      a reduction in melatonin or an increase in caspase-3, creatine kinase, and
      calcium ion may cause significant damage in brain due to chronic exposure of
      these radiations. These biomarkers clearly indicate possible health implications
      of such exposures.

PMID- 22134879
TI  - Glycoconjugates prevent B. anthracis toxin-induced cell death through binding
      while activating macrophages.
AB  - Bacillus anthracis toxins may be attenuated if macrophages could neutralize
      toxins upon contact or exposure. Glycoconjugate-bearing polymers, which have been
      shown to bind to Bacillus spores, were tested for recognition and binding of
      protective antigen (PA), lethal factor (LF), and edema factor (EF) toxins. We
      have demonstrated modulation of macrophage activity following exposure to these
      toxins. Without glycoconjugate (GC) activation, murine macrophages were killed by
      Bacillus toxins. GCs were shown to have a protective influence, sparing
      macrophages from toxin-induced cell death, as shown by increased macrophage cell
      viability based on trypan blue assay. Increased levels of inducible nitric oxide
      (NO) production by macrophages in presence of GCs suggest that GCs provide an
      activation signal for macrophages and stimulate their function. Results hint to
      GCs that promote neutralization of Bacillus toxins, block toxin-induced
      macrophage death, while increasing macrophage activation. Polymeric GCs may
      suggest novel approaches to improve existing or develop new vaccines as well as
      immunotherapeutics.

PMID- 22134880
TI  - Validity of the Oxford classification of IgA nephropathy in children.
AB  - BACKGROUND: In 2009, the Oxford classification of IgA nephropathy was published.
      However, its validity has not been fully examined in children. This study aimed
      to assess this system in an independent large-scale cohort of children. METHODS:
      We analyzed 161 consecutive children with newly diagnosed IgA nephropathy from
      1977 to 1989 retrospectively. We examined the ability of each variable in the
      Oxford classification as a predictor of renal outcome defined as >= stage III
      chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <60
      mL/min/1.73 m(2)) using Cox regression analysis. RESULTS: The mean mesangial
      score, and ratios of segmental glomerulosclerosis, endocapillary
      hypercellularity, tubular atrophy, and crescents were 0.49, 0.8%, 13.1%, 3.3%,
      and 9.2% respectively. Seven cases reached >= stage III CKD. In univariate
      analyses, mesangial hypercellularity score, endocapillary hypercellularity,
      tubular atrophy, and crescents were significant predictors of renal outcome. In a
      multivariate analysis, only mesangial hypercellularity score, tubular atrophy,
      and crescents were significant though, depending on models. Segmental
      glomerulosclerosis was not a significant predictor of renal outcome. Although the
      significance of crescents was not addressed in the Oxford classification,
      crescents were important predictors of outcome. CONCLUSIONS: The Oxford
      classification appears to be valid for predicting renal outcome in children.

PMID- 22134881
TI  - Tandem plasma-exchange and haemodialysis in a paediatric dialysis unit.
AB  - BACKGROUND: The simultaneous use of plasma-exchange (PE) and haemodialysis (HD),
      known as tandem PE and HD (TPH), may be an additional resource for treating
      patients who need both therapies at the same time. However, little experience is
      reported in the paediatric setting. CASE-DIAGNOSIS/TREATMENT: We retrospectively
      reviewed the TPH sessions performed in the last 5 years in our unit. Thirty-nine
      TPH treatments in eight pediatric patients were traced. The median age of the
      patients was 10.5 (range 5.1-19.2) years, and median weight was 27.6 (range 14.7
      66.2) kg. Indications for TPH were atypical haemolytic uremic syndrome due to
      factor H or factor I dysregulation, or to a not yet defined abnormality, in most
      of the sessions (34/39 sessions). The remaining five sessions were performed for
      vasculitis, focal segmental glomerulosclerosis and hyperimmunization in a patient
      waiting for kidney transplant. In all treatments, TPH was completed and reached
      the desired ultrafiltration and substitution volumes; the duration of PE was
      shorter than that of HD. No significant adverse events were observed.
      CONCLUSIONS: In those rare patients who require both PE and HD, TPH can improve
      their quality of life by reducing the time spent in extracorporeal circulation.
      This tandem treatment is safe and well-tolerated, even in subjects of relatively
      small body size.

PMID- 22134882
TI  - Distribution and targets of the relaxin-3 innervation of the septal area in the
      rat.
AB  - Neural tracing studies have revealed that the rat medial and lateral septum are
      targeted by ascending projections from the nucleus incertus, a population of
      tegmental GABA neurons. These neurons express the relaxin-family peptide, relaxin
      3, and pharmacological modulation of relaxin-3 receptors in medial septum alters
      hippocampal theta rhythm and spatial memory. In an effort to better understand
      the basis of these interactions, we have characterized the distribution of
      relaxin-3 fibers/terminals in relation to different septal neuron populations
      identified using established protein markers. Dense relaxin-3 fiber plexuses were
      observed in regions of medial septum containing hippocampal-projecting choline
      acetyltransferase (ChAT)-, neuronal nitric oxide synthase (nNOS)-, and
      parvalbumin (PV)-positive neurons. In lateral septum (LS), relaxin-3 fibers were
      concentrated in the ventrolateral nucleus of rostral LS and the ventral nucleus
      of caudal LS, with sparse labeling in the dorsolateral and medial nuclei of
      rostral LS, dorsal nucleus of caudal LS, and ventral portion nuclei. Relaxin-3
      fibers were also observed in the septofimbrial and triangular septal nuclei. In
      the medial septum, we observed relaxin-3-immunoreactive contacts with ChAT-, PV-,
      and glutamate decarboxylase-67-positive neurons that projected to hippocampus,
      and contacts between relaxin-3 terminals and calbindin- and calretinin-positive
      neurons. Relaxin-3 colocalized with synaptophysin in nerve terminals in all
      septal areas, and ultrastructural analysis revealed these terminals were
      symmetrical and contacted spines, somata, dendritic shafts, and occasionally
      other axonal terminals. These data predict that this GABA/peptidergic projection
      modulates septohippocampal activity and hippocampal theta rhythm related to
      exploratory navigation, defensive and ingestive behaviors, and responses to
      neurogenic stressors.

PMID- 22134883
TI  - Listening to music affects diurnal variation in muscle power output.
AB  - The purpose of this investigation was to assess the effects of listening to music
      while warming-up on the diurnal variations of power output during the Wingate
      test. 12 physical education students underwent four Wingate tests at 07:00 and
      17:00 h, after 10 min of warm-up with and without listening to music. The warm-up
      consisted of 10 min of pedalling at a constant pace of 60 rpm against a light
      load of 1 kg. During the Wingate test, peak and mean power were measured. The
      main finding was that peak and mean power improved from morning to afternoon
      after no music warm-up (p<0.001 and p<0.01, respectively). These diurnal
      variations disappeared for mean power and persisted with an attenuated morning
      evening difference (p<0.05) for peak power after music warm-up. Moreover, peak
      and mean power were significantly higher after music than no music warm-up during
      the two times of testing. Thus, as it is a legal method and an additional aid,
      music should be used during warm-up before performing activities requiring
      powerful lower limbs' muscles contractions, especially in the morning competitive
      events.

PMID- 22134884
TI  - MtDNA haplogroups and elite Korean athlete status.
AB  - Mitochondrial DNA (mtDNA) variation has recently been suggested to have an
      association with athletic performance or physical endurance. Since mtDNA is
      haploid and lacks recombination, specific mutations in the mtDNA genome
      associated with human exercise tolerance or intolerance arise and remain in
      particular genetic backgrounds referred to as haplogroups. To assess the possible
      contribution of mtDNA haplogroup-specific variants to differences in elite
      athletic performance, we performed a population-based study of 152 Korean elite
      athletes [77 sprint/power athletes (SPA) and 75 endurance/middle-power athletes
      (EMA)] and 265 non-athletic controls (CON). The overall haplogroup distribution
      of EMA differed significantly from CON (p<0.01), but that of SPA did not. The EMA
      have an excess of haplogroups M* (OR 4.38, 95% CI 1.63-11.79, p=0.003) and N9 (OR
      2.32, 95% CI 0.92-5.81, p=0.042), but a dearth of haplogroup B (OR 0.26, 95% CI
      0.09-0.75, p=0.003) compared with the CON. Thus, our data imply that specific
      mtDNA lineages may provide a significant effect on elite Korean endurance status,
      although functional studies with larger sample sizes are necessary to further
      substantiate these findings.

PMID- 22134885
TI  - Subject-specific estimation of respiratory navigator tracking factor for free
      breathing cardiovascular MR.
AB  - A mean respiratory navigator tracking factor of 0.6 is commonly used to estimate
      the respiratory motion of the heart from the displacement of the right hemi
      diaphragm. A constant tracking factor can generate significant residual error in
      estimation of the respiratory motion of the heart for the cases where the actual
      tracking factor highly deviates from 0.6. In this study, we implemented and
      evaluated a robust method to calculate a subject-specific tracking factor for
      free-breathing high resolution cardiac MR. The subject-specific tracking factor
      was calculated from two consecutive navigator signals placed on the right hemi
      diaphragm and the basal left ventricle in a training phase. To verify the
      accuracy of the estimated subject-specific tracking factor, nineteen subjects
      were recruited for comparing the estimated tracking factor in real-time with an
      image-based tracking factor, calculated off-line. Subsequently, in seven adult
      subjects, whole-heart or targeted coronary artery MR images were acquired using
      the estimated subject-specific tracking factor and visually compared with those
      acquired using a constant (0.6) tracking factor. It was shown that the proposed
      method can accurately estimate the subject-specific tracking factor and improve
      the quality of coronary images when the subject-specific tracking factor differs
      from 0.6.

PMID- 22134886
TI  - Vascular patterning and permeability in prostate cancer models with differing
      osteogenic properties.
AB  - Bone metastasis is a major cause of morbidity and mortality in prostate cancer.
      However, the lack of clinically relevant models hinders our understanding of the
      disease as well as development of effective therapies and imaging approaches. We
      used noninvasive MRI, histology and micro CT to further characterize the newly
      established prostate cancer bone metastases-derived model MDA-PCa-118b, and to
      compare it to the well-established PC-3MM2 model with regard to bone structure
      and vascular patterning. The PC-3MM2 model is highly osteolytic whereas the MDA
      PCa-118b model shows a robust osteoblastic reaction, as often seen in clinical
      cases. Macromolecular contrast enhanced MRI revealed differences in vascular
      permeability patterns, which appeared peripheral for PC-3MM2 and nodular for MDA
      PCa-118b, matching the microscopic cellular composition of each model: PC-3MM2
      exclusively recruits endothelial cells to form thin tumor-core blood vessels and
      enlarged, leaky peripheral vessels, whereas MDA-PCa-118b also recruits bone
      forming cells and pericytes such that small tumor nests are encircled with leaky
      vessels and embedded in bone-like tissue dotted with pericyte-covered vessels.
      Despite these structural differences, vascular permeability was reduced in both
      tumor models by either imatinib or SU10944 treatment. This study highlights the
      importance of clinically relevant osteogenic models of human prostate cancer and
      the value of such models not only in enhancing our understanding of
      tumorigenesis, metastasis and response to therapy, but also for development of
      appropriate methods for noninvasive imaging of these processes.

PMID- 22134887
TI  - Chemical reduction of carboxyl groups in heparin abolishes its vasodilatory
      activity.
AB  - Previous studies have shown that heparin induces vascular relaxation via integrin
      dependent nitric oxide (NO)-mediated activation of the muscarinic receptor. The
      aim of this study was to identify the structural features of heparin that are
      necessary for the induction of vasodilatation. To address this issue, we tested
      heparin from various sources for their vasodilatation activities in the rat aorta
      ring. Structural and chemical characteristics of heparin, such as its molecular
      weight and substitution pattern, did not show a direct correlation with the
      vasodilation activity. Principal component analysis (PCA) of circular dichroism
      (CD), (1)H-nuclear magnetic resonance (NMR) and vasodilation activity
      measurements confirmed that there is no direct relationship between the physico
      chemical nature and vasodilation activity of the tested heparin samples. To
      further understand these observations, unfractionated heparin (UFH) from bovine
      intestinal mucosa, which showed the highest relaxation effect, was chemically
      modified. Interestingly, non-specific O- and N-desulfation of heparin reduced its
      anticoagulant, antithrombotic, and antihemostatic activities, but had no effect
      on its ability to induce vasodilation. On the other hand, chemical reduction of
      the carboxyl groups abolished heparin-induced vasodilation and reduced the
      affinity of heparin toward the extracellular matrix (ECM). In addition, dextran
      and dextran sulfate (linear non-sulfated and highly sulfated polysaccharides,
      respectively) did not induce significant relaxation, showing that the
      vasodilation activity of polysaccharides is neither charge-dependent nor backbone
      unspecific. Our results suggest that desulfated heparin molecules may be used as
      vasoactive agents due to their low side effects.

PMID- 22134888
TI  - Immunoreceptor signaling.

PMID- 22134891
TI  - Palladium(II)-catalyzed stereospecific three-component domino reactions of diyne
      enones, nucleophiles, and vinyl ketones.

PMID- 22134889
TI  - Abcg2 expression marks tissue-specific stem cells in multiple organs in a mouse
      progeny tracking model.
AB  - The side population phenotype is associated with the Hoechst dye efflux activity
      of the Abcg2 transporter and identifies hematopoietic stem cells (HSCs) in the
      bone marrow. This association suggests the direct use of Abcg2 expression to
      identify adult stem cells in various other organs. We have generated a lineage
      tracing mouse model based on an allele that coexpresses both Abcg2 and a CreERT2
      expression cassette. By crossing these mice with lox-STOP-lox reporter lines
      (LacZ or YFP), cells that express Abcg2 and their progeny were identified
      following treatment with tamoxifen (Tam). In the liver and kidney, in which
      mature cells express Abcg2, reporter gene expression verified the expected
      physiologic expression pattern of the recombinant allele. Long-term marking of
      HSCs was seen in multiple peripheral blood lineages from adult mice,
      demonstrating that Abcg2(+) bone marrow HSCs contribute to steady-state
      hematopoiesis. Stem cell tracing patterns were seen in the small intestine and in
      seminiferous tubules in the testis 20 months after Tam treatment, proving that
      stem cells from these organs express Abcg2. Interstitial cells from skeletal and
      cardiac muscle were labeled, and some cells were costained with endothelial
      markers, raising the possibility that these cells may function in the repair
      response to muscle injury. Altogether, these studies prove that Abcg2 is a stem
      cell marker for blood, small intestine, testicular germ cells, and possibly for
      injured skeletal and/or cardiac muscle and provide a new model for studying stem
      cell activity that does not require transplant-based assays.

PMID- 22134892
TI  - Proline alters antioxidant enzyme defenses and lipoperoxidation in the
      erythrocytes and plasma of rats: in vitro and in vivo studies.
AB  - In the present study, we investigated, in vivo (acute and chronic) and in vitro,
      the effects of proline on the activities of antioxidant enzymes such as catalase
      (CAT), glutathione peroxidase and superoxide dismutase (SOD) in erythrocytes and
      also investigated the effect on thiobarbituric acid-reactive substances (TBARS)
      in the plasma of rats. For the experiments, the number of animals per group
      ranged from eight to ten. For acute administration, 29-day-old rats received one
      subcutaneous injection of proline (18.2 MUmol/g body weight) or an equivalent
      volume of 0.9% saline solution (control) and were killed 1 h later. For chronic
      treatment, buffered proline was injected subcutaneously into rats twice a day at
      10 h intervals from the 6th to the 28th day of age. Rats were killed 12 h after
      the last injection. For in vitro studies, proline (30.0 MUM to 1.0 mM) was added
      to the incubation medium. Results showed that acute administration of proline
      reduced CAT and increased SOD activities, while chronic treatment increased the
      activities of CAT and SOD in erythrocytes and TBARS in the plasma of rats.
      Furthermore, in vitro studies showed that proline increased TBARS in the plasma
      (0.5 and 1.0 mM) and CAT activity (1.0 mM) in the erythrocytes of rats. The
      influence of the antioxidants (alpha-tocopherol plus ascorbic acid) on the
      effects elicited by proline was also studied. Treatment with antioxidants for 1
      week or from the 6th to the 28th day of age prevented the alterations caused by
      acute and chronic, respectively, proline administration on the oxidative
      parameters evaluated. Data indicate that proline alters antioxidant defenses and
      induces lipid peroxidation in the blood of rats.

PMID- 22134893
TI  - Jeju ground water containing vanadium enhances antioxidant systems in human liver
      cells.
AB  - Vanadium compounds have shown promise in the treatment of diabetes and in cancer
      prevention. The aim of this study is to investigate the effects of Jeju ground
      water, containing the vanadium compounds S1 (8.0 +/- 0.9 MUg/l) and S3 (26.0 +/-
      2.0 MUg/l), and of vanadyl sulfate (VOSO(4), 26 MUg/l) on antioxidant systems in
      human Chang liver cells. Cells were incubated for ten passages in media
      containing deionized distilled water, Jeju ground water (S1, S3), or VOSO(4). S1
      and S3 increased the gene and protein expression and the enzymatic activities of
      antioxidant enzymes, including superoxide dismutase, catalase, glutathione
      peroxidase, and heme oxygenase. VOSO(4) was likewise found to improve mRNA and
      protein expression as well as the activities of these enzymes. Taken together,
      these results suggest that the antioxidant properties of Jeju ground water,
      containing vanadium compounds, and of vanadyl sulfate were due to stimulatory
      effects on antioxidant enzyme activities and antioxidant enzyme expression.

PMID- 22134894
TI  - Spectral Hounsfield units: a new radiological concept.
AB  - OBJECTIVE: Computed tomography (CT) uses radiographical density to depict
      different materials; although different elements have different absorption
      fingerprints across the range of diagnostic X-ray energies, this spectral
      absorption information is lost in conventional CT. The recent development of dual
      energy CT (DECT) allows extraction of this information to a useful but limited
      extent. However, the advent of new photon counting chips that have energy
      resolution capabilities has put multi-energy or spectral CT (SCT) on the clinical
      horizon. METHODS: This paper uses a prototype SCT system to demonstrate how CT
      density measurements vary with kilovoltage. RESULTS: While radiologists learn
      about linear attenuation curves during radiology training, they do not usually
      need a detailed understanding of this phenomenon in their clinical practice.
      However SCT requires a paradigm shift in how radiologists think about CT density.
      CONCLUSION: Because radiologists are already familiar with the Hounsfield Unit
      (HU), it is proposed that a modified HU be used that includes the mean energy
      used to obtain the image, as a conceptual bridge between conventional CT and SCT.
      A suggested format would be: HU(keV). KEY POINTS: * Spectral computed tomography
      uses K-edge and slope effects to identify element signatures. * New visualisation
      tools will be required to efficiently display spectral CT information. * This
      paper demonstrates HU variation with keV using the Medipix3 chip. * HU ( keV ) is
      a suggested format when stating spectral HU measurements.

PMID- 22134896
TI  - Magnetic resonance in tissue engineering.

PMID- 22134895
TI  - Kv7.5 is the primary Kv7 subunit expressed in C-fibers.
AB  - Kv7 (KCNQ) potassium channel openers (enhancers) decrease neuropathic pain in
      experimental models. Here we show that C-fibers, and their associated small
      diameter neurons in the dorsal root ganglia (both IB4- and TrkA-positive),
      expressed Kv7.5. In contrast, C-fibers did not express detectable levels of Kv7.2
      or Kv7.3, which are instead localized to nodes of Ranvier and the cell bodies of
      large sensory neurons. These data suggest that Kv7.5 provides the primary M
      current in nociceptive neurons.

PMID- 22134898
TI  - Factors affecting chemical-based purification of DNA from Saccharomyces
      cerevisiae.
AB  - Extraction of high molecular weight chromosomal DNA from yeast cells is a
      procedure that is performed frequently for experiments involving polymerase chain
      reaction (PCR), Southern blotting and other DNA analysis techniques. We have
      investigated several parameters affecting DNA yield and quality, using a simple
      chemical-based purification procedure that was modelled on alkaline lysis methods
      developed for bacterial cells. The three major steps of the procedure, cell
      lysis, protein removal and DNA precipitation, were optimized by testing the
      impacts of several chemicals, including sodium dodecyl sulphate (SDS), sodium
      hydroxide, Tris buffer, sodium acetate and potassium acetate. Other parameters,
      such as the effect of elevated temperatures on cell lysis, were also
      investigated. A rapid, optimized protocol was derived for the purification of DNA
      from small cell cultures that can be readily digested with restriction enzymes
      and used as a template for PCR. Average yield was calculated to be approximately
      1.7 ug DNA/10(8) cells, which is similar to the theoretical maximum amount
      obtainable from haploid yeast cells.

PMID- 22134899
TI  - The JMJD2A demethylase regulates apoptosis and proliferation in colon cancer
      cells.
AB  - JMJD2A is a transcriptional cofactor and enzyme that catalyzes demethylation of
      histone H3 lysines 9 and 36 and is overexpressed in human tumors, but its role in
      oncogenesis remains unclear. Here, we show that JMJD2A interacts with the tumor
      suppressor p53 both in vitro and in HCT116 colon cancer cells. Chromatin
      immunoprecipitation assays demonstrated that JMJD2A was recruited together with
      p53 to the promoter of the p21 cell cycle inhibitor upon stimulation with the DNA
      damaging agent, adriamycin. Downregulation of JMJD2A resulted in increased
      expression of p21 and of the pro-apoptotic Puma protein, whereas levels of the
      anti-apoptotic Bcl-2 protein were decreased. Furthermore, JMJD2A knock-down led
      to reduced HCT116, DLD-1 and HT-29 colon cancer cell proliferation, while
      overexpression of JMJD2A enhanced HCT116 proliferation in low serum media.
      Finally, JMJD2A depletion induced apoptosis in HCT116 cells and this effect was
      less pronounced in the absence of p53. Collectively, these data indicate that
      JMJD2A is a novel promoter of colon cancer cell proliferation and survival, which
      mediates its effects in p53-dependent and -independent ways. JMJD2A may therefore
      be a valid target to sensitize tumor cells to chemotherapy-induced cell death and
      growth suppression.

PMID- 22134900
TI  - Rhodium-catalyzed, highly enantioselective 1,2-addition of aryl boronic acids to
      alpha-ketoesters and alpha-diketones using simple, chiral sulfur-olefin ligands.

PMID- 22134902
TI  - Evidence for LiBr-assisted generation of a silylene from a 1,2-diaryl-1,2
      dibromodisilene.

PMID- 22134901
TI  - Nuclear factor kappa B signaling initiates early differentiation of neural stem
      cells.
AB  - Inflammatory mediators, many of which activate the signaling of nuclear factor
      kappa B (NFkappaB), have received increasing attention in the field of
      neurogenesis. NFkappaB signaling regulates neurite outgrowth and neural
      plasticity as well as the proliferation/apoptosis and terminal differentiation of
      neural stem cells (NSCs). Early neurogenesis from NSCs produces identical progeny
      through symmetric division and committed daughter cells through asymmetric
      division. Here, we show that NFkappaB signaling is required for NSC initial
      differentiation. The canonical IKKbeta/IkappaBalpha/p65 pathway is activated
      during the initial stages of neural differentiation induced by treatment with
      TNFalpha or withdrawal of epidermal growth factor/basic fibroblast growth factor.
      NSC-specific inhibition of NFkappaB in transgenic mice causes an accumulation of
      Nestin(+) /Sox2(+) /glial fibrillary acidic protein(+) NSCs. Inhibition of
      NFkappaB signaling in vitro blocks differentiation and asymmetric division and
      maintains NSCs in an undifferentiated state. The induction of initial
      differentiation and asymmetry by NFkappaB signaling occurs through the inhibition
      of C/EBPbeta expression. Our data reveal a novel function of NFkappaB signaling
      in early neurogenesis and provide insight into the molecular mechanisms
      underlying neurodevelopmental disorders and neurodegenerative diseases.

PMID- 22134903
TI  - Ca2+ store depletion and endoplasmic reticulum stress are involved in P2X7
      receptor-mediated neurotoxicity in differentiated NG108-15 cells.
AB  - P2X7 receptor (P2X7R) activation by extracellular ATP triggers influx of Na(+)
      and Ca(2+), cytosolic Ca(2+) overload and consequently cytotoxicity. Whether
      disturbances in endoplasmic reticulum (ER) Ca(2+) homeostasis and ER stress are
      involved in P2X7R-mediated cell death is unknown. In this study, a P2X7R agonist
      (BzATP) was used to activate P2X7R in differentiated NG108-15 neuronal cells. In
      a concentration-dependent manner, application of BzATP (10-100 uM) immediately
      raised cytosolic Ca(2+) concentration ([Ca(2+)]i) and caused cell death after a
      24-h incubation. P2X7R activation for 2 h did not cause cell death but resulted
      in a sustained reduction in ER Ca2+ pool size, as evidenced by a diminished
      cyclopiazonic acid-induced Ca(2+) discharge (fura 2 assay) and a lower
      fluorescent signal in cells loaded with Mag-fura 2 (ER-specific Ca(2+)
      fluorescent dye). Furthermore, P2X7R activation (2 h) led to the appearance of
      markers of ER stress [phosphorylated alpha subunit of eukaryotic initiation
      factor 2 (p-eIF2alpha) and C/EBP homologous protein (CHOP)] and apoptosis
      (cleaved caspase 3). Xestospongin C (XeC), an antagonist of inositol-1,4,5
      trisphosphate (IP3) receptor (IP3R), strongly inhibited BzATP-triggered [Ca(2+)]i
      elevation, suggesting that the latter involved Ca(2+) release via IP3R. XeC
      pretreatment not only attenuated the reduction in Ca(2+) pool size in BzATP
      treated cells, but also rescued cell death and prevented BzATP-induced appearance
      of ER stress and apoptotic markers. These novel observations suggest that P2X7R
      activation caused not only Ca(2+) overload, but also Ca(2+) release via IP3R,
      sustained Ca(2+) store depletion, ER stress and eventually apoptotic cell death.

PMID- 22134904
TI  - Switchable intermolecular communication in a four-fold rotaxane.

PMID- 22134905
TI  - The cost of stroke and transient ischaemic attack in Ireland: a prevalence-based
      estimate.
AB  - BACKGROUND: stroke is a leading cause of death and disability globally. The
      economic costs of stroke are high but not often fully quantified. This paper
      estimates the economic burden of stroke and transient ischaemic attack (TIA) in
      Ireland in 2007. METHODS: a prevalence-based approach using a societal
      perspective is adopted. Both direct and indirect costs are estimated. RESULTS:
      total stroke costs are estimated to have been ?489-?805 million in 2007,
      comprising ?345-?557 million in direct costs and ?143-?248 million in indirect
      costs. Nursing home care and indirect costs together account for the largest
      proportion of total stroke costs (74-82%). The total cost of TIA was
      approximately ?11.1 million in 2007, with acute hospital care accounting for 90%
      of the total. CONCLUSIONS: the chronic phase of the disease accounts for the
      largest proportion of the total annual economic burden of stroke. This highlights
      the need to maximise functional outcomes to lessen the longer term economic and
      personal impacts of stroke.

PMID- 22134906
TI  - It's all in the timing.

PMID- 22134907
TI  - PET-CT in MM: a new definition of CR.

PMID- 22134908
TI  - Repertoire isn't everything for GVHD.

PMID- 22134909
TI  - [Too busy to think?].
AB  - A synthesis of current nursing knowledge by means of nursing theory construction
      is missing in German speaking countries. Unfortunately, due to this the nursing
      discipline cannot counterbalance the influence of other scientific disciplines
      with a self-created nursing specific theory. The level of theory construction in
      a discipline serves as sensitive indicator of intellectual state in this
      discipline. After the fruitful period from 1980 to 1990, the theoretical
      discourse in nursing almost disrupted while the number of empirical studies is
      increasing. This deserves to be discussed thoroughly with respect to further
      development of nursing theory. The theoretical discourse in nursing should
      generalise research findings in order to develop nursing theory in an inductive
      way - combined with a focus on patient's perspective in research and theory
      construction. New aspects and themes in health care as the demographical
      development and its epidemiological consequences, the increase and transformation
      of chronic illness as well as the changing role of the patient (participation,
      self-management) should be considered. The reanimation of a culture of discussion
      is only possible if scholars can dedicate time to it. Only under this condition
      reading and discussing research findings of other disciplines will be again on
      the agenda of scientific working and will - last but not least - inspire the
      construction of a nursing specific theory.

PMID- 22134910
TI  - [The contibution of concept development to nursing knowledge? The example of
      transitoriness].
AB  - To provide nursing practice with evidence, it is important to understand nursing
      phenomena in detail. Therefore, good descriptions including the identification of
      characteristics and attributes of nursing phenomena on various levels of
      abstraction, i. e., concepts, are needed. In this article the significance of
      concept development for nursing science will be demonstrated by drawing on the
      example of 'transitoriness'. The evolutionary concept analysis proposed by
      Rodgers (2000) is introduced in more detail. Drawing on transitoriness, the
      phenomenon is presented with the help of the evolutionary concept analysis by
      Rodgers (2000). The phenomenon's characteristics and attributes are identified,
      as well as potential areas of application. Moreover, areas are outlined, in which
      interventions for nursing practice can be developed, implemented and evaluated.
      Thus, nursing practice is updated to include new findings and innovation. Through
      concept analysis nursing phenomena can be described in more detail, enhanced or
      broadened for use in nursing practice. Such structured processes as concept
      analysis can be employed successfully for other nursing phenomena. Concept
      analyses can lead to the identification of tasks for the respective scientific
      discipline and professionals. Thus, concept analyses can lead to the
      concretisation of tasks in nursing.

PMID- 22134911
TI  - ["Out of interest in reasonable conditions... " Relevance and constitutive
      elements of a critical theory in nursing science].
AB  - Nursing practice needs a theoretical foundation. As in any other discipline,
      theories form the core of nursing science. They contribute to the definition of
      nursing and to the evolution of professional domains. Depending on their level of
      abstraction and their range ("grand theories") they can guide actions, have an
      orientating, but also a critical function. Furthermore, theories serve to
      legitimate and justify nursing in the public. This is especially important, if
      politics and society have high expectations in the nursing profession. The
      current concept of a critical theory of nursing science has a critical focus on
      repressions and deficits in nursing practice, but also is aimed at achieving
      reasonable nursing practice. This theory is emancipatorical and normative as
      well. It is following Foucault's analysis of power and explicating the "Frankfurt
      School of Critical Theory" as a critique of the conditions of working,
      understanding, recognising, self, time and nature.

PMID- 22134912
TI  - [Nursing theories - the forgotten dimension? A retrospective view to and a
      reflection about the article "Nursing theories are essential to professional
      nursing" (Pflege, 1989)].

PMID- 22134913
TI  - Equivalence of double and single wave vector diffusion contrast at low diffusion
      weighting.
AB  - Multiple pulsed field gradient diffusion sequences have received renewed interest
      in recent years as a potentially new type of MRI contrast. This attention is
      largely a result of the ability to measure pore sizes using low-amplitude
      diffusion gradients, and to distinguish between macroscopically isotropic systems
      of anisotropic pores and systems of isotropic pores. In this article, it is shown
      that, under many circumstances, the same type of information can be obtained by
      combining two or more standard single pulse diffusion-weighted experiments
      acquired at different diffusion times. Similarly, information from multiple
      pulsed field gradient diffusion can be reconstructed from several single pulsed
      diffusion experiments. This possibility is rooted in the information contained in
      the time dependence of the diffusion tensor, which provides a complete
      description of the diffusion-weighted MR signal at low gradient amplitudes. The
      new information arising at the fourth order in the cumulant expansion is
      discussed. The coupling of the wave vectors at long mixing times is found to be
      controlled by the variance of the single pore mean displacement tensor. In
      particular, a discussion is given concerning the way in which the sensitivity of
      the fourth-order term to the pore shape anisotropy is modulated by pore
      orientation anisotropy and vanishes in coherently oriented homogeneous ensembles.
      For macroscopically isotropic systems, a new index of pore shape anisotropy is
      proposed.

PMID- 22134914
TI  - Rapamycin and glucose-target of rapamycin (TOR) protein signaling in plants.
AB  - Target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator
      that integrates energy, nutrients, growth factors, and stress signals to promote
      survival and growth in all eukaryotes. The reported land plant resistance to
      rapamycin and the embryo lethality of the Arabidopsis tor mutants have hindered
      functional dissection of TOR signaling in plants. We developed sensitive cellular
      and seedling assays to monitor endogenous Arabidopsis TOR activity based on its
      conserved S6 kinase (S6K) phosphorylation. Surprisingly, rapamycin effectively
      inhibits Arabidopsis TOR-S6K1 signaling and retards glucose-mediated root and
      leaf growth, mimicking estradiol-inducible tor mutants. Rapamycin inhibition is
      relieved in transgenic plants deficient in Arabidopsis FK506-binding protein 12
      (FKP12), whereas FKP12 overexpression dramatically enhances rapamycin
      sensitivity. The role of Arabidopsis FKP12 is highly specific as overexpression
      of seven closely related FKP proteins fails to increase rapamycin sensitivity.
      Rapamycin exerts TOR inhibition by inducing direct interaction between the TOR
      FRB (FKP-rapamycin binding) domain and FKP12 in plant cells. We suggest that
      variable endogenous FKP12 protein levels may underlie the molecular explanation
      for longstanding enigmatic observations on inconsistent rapamycin resistance in
      plants and in various mammalian cell lines or diverse animal cell types.
      Integrative analyses with rapamycin and conditional tor and fkp12 mutants also
      reveal a central role of glucose-TOR signaling in root hair formation. Our
      studies demonstrate the power of chemical genetic approaches in the discovery of
      previously unknown and pivotal functions of glucose-TOR signaling in governing
      the growth of cotyledons, true leaves, petioles, and primary and secondary roots
      and root hairs.

PMID- 22134915
TI  - Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase
      early amyloid-like oligomers and their implication in alpha-synuclein
      aggregation.
AB  - Lewy bodies and Lewy neurites, neuropathological hallmarks of several
      neurological diseases, are mainly made of filamentous assemblies of alpha
      synuclein. However, other macromolecules including Tau, ubiquitin, glyceraldehyde
      3-phosphate dehydrogenase, and glycosaminoglycans are routinely found associated
      with these amyloid deposits. Glyceraldehyde-3-phosphate dehydrogenase is a
      glycolytic enzyme that can form fibrillar aggregates in the presence of acidic
      membranes, but its role in Parkinson disease is still unknown. In this work, the
      ability of heparin to trigger the amyloid aggregation of this protein at
      physiological conditions of pH and temperature is demonstrated by infrared and
      fluorescence spectroscopy, dynamic light scattering, small angle x-ray
      scattering, circular dichroism, and fluorescence microscopy. Aggregation proceeds
      through the formation of short rod-like oligomers, which elongates in one
      dimension. Heparan sulfate was also capable of inducing glyceraldehyde-3
      phosphate dehydrogenase aggregation, but chondroitin sulfates A, B, and C
      together with dextran sulfate had a negligible effect. Aided with molecular
      docking simulations, a putative binding site on the protein is proposed providing
      a rational explanation for the structural specificity of heparin and heparan
      sulfate. Finally, it is demonstrated that in vitro the early oligomers present in
      the glyceraldehyde-3-phosphate dehydrogenase fibrillation pathway promote alpha
      synuclein aggregation. Taking into account the toxicity of alpha-synuclein
      prefibrillar species, the heparin-induced glyceraldehyde-3-phosphate
      dehydrogenase early oligomers might come in useful as a novel therapeutic
      strategy in Parkinson disease and other synucleinopathies.

PMID- 22134916
TI  - Dentin phosphoprotein (DPP) activates integrin-mediated anchorage-dependent
      signals in undifferentiated mesenchymal cells.
AB  - Dentin phosphoprotein (DPP), a major noncollagenous protein of the dentin matrix,
      is a highly acidic protein that binds Ca(2+) avidly and is thus linked to matrix
      mineralization. Here, we demonstrate that the RGD domain in DPP can bind to
      integrins on the cell surface of undifferentiated mesenchymal stem cells and pulp
      cells. This coupling generates intracellular signals that are channeled along
      cytoskeletal filaments and activate the non-receptor tyrosine kinase focal
      adhesion kinase, which plays a key role in signaling at sites of cellular
      adhesion. The putative focal adhesion kinase autophosphorylation site Tyr(397) is
      phosphorylated during focal adhesion assembly induced by DPP on the substrate. We
      further demonstrate that these intracellular signals propagate through the
      cytoplasm and activate anchorage-dependent ERK signaling. Activated ERK
      translocates to the nucleus and phosphorylates the transcription factor ELK-1,
      which in turn coordinates the expression of downstream target genes such as DMP1
      and dentin sialoprotein (DSP). These studies suggest a novel paradigm
      demonstrating that extracellular DPP can induce intracellular signaling that can
      be propagated to the nucleus and thus alter gene activities.

PMID- 22134917
TI  - Two-partner secretion of gram-negative bacteria: a single beta-barrel protein
      enables transport across the outer membrane.
AB  - The mechanisms of protein secretion by pathogenic bacteria remain poorly
      understood. In gram-negative bacteria, the two-partner secretion pathway exports
      large, mostly virulence-related "TpsA" proteins across the outer membrane via
      their dedicated "TpsB" transporters. TpsB transporters belong to the ubiquitous
      Omp85 superfamily, whose members are involved in protein translocation across, or
      integration into, cellular membranes. The filamentous hemagglutinin/FhaC pair of
      Bordetella pertussis is a model two-partner secretion system. We have
      reconstituted the TpsB transporter FhaC into proteoliposomes and demonstrate that
      FhaC is the sole outer membrane protein required for translocation of its cognate
      TpsA protein. This is the first in vitro system for analyzing protein secretion
      across the outer membrane of gram-negative bacteria. Our data also provide clear
      evidence for the protein translocation function of Omp85 transporters.

PMID- 22134918
TI  - Hydrolysis of secreted sialoglycoprotein immunoglobulin A (IgA) in ex vivo and
      biochemical models of bacterial vaginosis.
AB  - Bacterial vaginosis (BV) is a common polymicrobial imbalance of the vaginal flora
      associated with a wide variety of obstetric and gynecologic complications
      including serious infections and preterm birth. As evidenced by high recurrence
      rates following treatment, interventions for BV are still lacking. Several
      hydrolytic activities, including glycosidases and proteases, have been previously
      correlated with BV and have been hypothesized to degrade host sialoglycoproteins
      that participate in mucosal immune functions. Sialidase activity is most
      predictive of BV status and correlates strongly with adverse health outcomes.
      Here we combine clinical specimens with biochemical approaches to investigate
      secretory immunoglobulin A (SIgA) as a substrate of BV-associated glycosidases
      and proteases. We show that BV clinical specimens hydrolyze sialic acid from
      SIgA, but not in the presence of the sialidase inhibitor dehydro-deoxy-sialic
      acid. The collective action of BV-associated glycosidases exposes underlying
      mannose residues of SIgA, most apparent on the heavily N-glycosylated secretory
      component of the antibody. Terminal sialic acid residues on SIgA protect
      underlying carbohydrate residues from exposure and hydrolysis by exoglycosidases
      (galactosidase and hexosaminidase). It is known that both IgG and SIgA are
      present in the human reproductive tract. We show that the IgG heavy chain is more
      susceptible to proteolysis than its IgA counterpart. Gentle partial
      deglycosylation of the SIgA secretory component enhanced susceptibility to
      proteolysis. Together, these data support a model of BV in which SIgA is subject
      to stepwise exodeglycosylation and enhanced proteolysis, likely compromising the
      ability of the reproductive mucosa to neutralize and eliminate pathogens.

PMID- 22134919
TI  - Comparative lipidomic analysis of mouse and human brain with Alzheimer disease.
AB  - Lipids are key regulators of brain function and have been increasingly implicated
      in neurodegenerative disorders including Alzheimer disease (AD). Here, a systems
      based approach was employed to determine the lipidome of brain tissues affected
      by AD. Specifically, we used liquid chromatography-mass spectrometry to profile
      extracts from the prefrontal cortex, entorhinal cortex, and cerebellum of late
      onset AD (LOAD) patients, as well as the forebrain of three transgenic familial
      AD (FAD) mouse models. Although the cerebellum lacked major alterations in lipid
      composition, we found an elevation of a signaling pool of diacylglycerol as well
      as sphingolipids in the prefrontal cortex of AD patients. Furthermore, the
      diseased entorhinal cortex showed specific enrichment of lysobisphosphatidic
      acid, sphingomyelin, the ganglioside GM3, and cholesterol esters, all of which
      suggest common pathogenic mechanisms associated with endolysosomal storage
      disorders. Importantly, a significant increase in cholesterol esters and GM3 was
      recapitulated in the transgenic FAD models, suggesting that these mice are
      relevant tools to study aberrant lipid metabolism of endolysosomal dysfunction
      associated with AD. Finally, genetic ablation of phospholipase D(2), which
      rescues the synaptic and behavioral deficits of an FAD mouse model, fully
      normalizes GM3 levels. These data thus unmask a cross-talk between the metabolism
      of phosphatidic acid, the product of phospholipase D(2), and gangliosides, and
      point to a central role of ganglioside anomalies in AD pathogenesis. Overall, our
      study highlights the hypothesis generating potential of lipidomics and identifies
      novel region-specific lipid anomalies potentially linked to AD pathogenesis.

PMID- 22134920
TI  - Regulation of peroxisomal lipid metabolism by catalytic activity of tumor
      suppressor H-rev107.
AB  - H-rev107 is a mammalian protein belonging to the HRAS-like suppressor family.
      Although the protein was originally found as a tumor suppressor, currently it is
      receiving considerable attention as a regulator of adipocyte lipolysis. We
      recently revealed that purified recombinant H-rev107 has phospholipase A(1/2)
      activity, releasing free fatty acids from glycerophospholipids with a preference
      for esterolysis at the sn-1 position. In the present study, we constitutively
      expressed H-rev107 in cloned HEK293 cells to examine its biological function in
      living cells. Initially, the cells accumulated free fatty acids. We also found a
      remarkable decrease in the levels of ether-type lipids, including plasmalogen and
      ether-type triglyceride, with a concomitant increase in fatty alcohols,
      substrates for the biosynthesis of ether-type lipids. Considering that
      peroxisomes are involved in the ether-type lipid biosynthesis, we next focused on
      peroxisomes and found that the peroxisomal markers 70-kDa peroxisomal membrane
      protein and catalase were abnormally distributed in the transfected cells. These
      biochemical and morphological abnormalities were not seen in HEK293 cells stably
      expressing a catalytically inactive mutant of H-rev107. When H-rev107 or its
      fusion protein with enhanced green fluorescence protein was transiently expressed
      in mammalian cells, both proteins were associated with peroxisomes in some of the
      observed cells. These results suggest that H-rev107 interferes with the
      biosynthesis of ether-type lipids and is responsible for the dysfunction of
      peroxisomes in H-rev107-expressing cells.

PMID- 22134921
TI  - Insulin-like growth factor binding protein-4 differentially inhibits growth
      factor-induced angiogenesis.
AB  - An in-depth understanding of the molecular and cellular complexity of
      angiogenesis continues to advance as new stimulators and inhibitors of blood
      vessel formation are uncovered. Gaining a more complete understanding of the
      response of blood vessels to both stimulatory and inhibitory molecules will
      likely contribute to more effective strategies to control pathological
      angiogenesis. Here, we provide evidence that endothelial cell interactions with
      structurally altered collagen type IV may suppress the expression of insulin-like
      growth factor binding protein-4 (IGFBP-4), a well documented inhibitor of the IGF
      1/IGF-1R signaling axis. We report for the first time that IGFBP-4 differentially
      inhibits angiogenesis induced by distinct growth factor signaling pathways as
      IGFBP-4 inhibited FGF-2- and IGF-1-stimulated angiogenesis but failed to inhibit
      VEGF-induced angiogenesis. The resistance of VEGF-stimulated angiogenesis to
      IGFBP-4 inhibition appears to depend on sustained activation of p38 MAPK as
      blocking its activity restored the anti-angiogenic effects of IGFBP-4 on VEGF
      induced blood vessel growth in vivo. These novel findings provide new insight
      into how blood vessels respond to endogenous inhibitors during angiogenesis
      stimulated by distinct growth factor signaling pathways.

PMID- 22134922
TI  - Nuclear envelope phosphatase 1-regulatory subunit 1 (formerly TMEM188) is the
      metazoan Spo7p ortholog and functions in the lipin activation pathway.
AB  - Lipin-1 catalyzes the formation of diacylglycerol from phosphatidic acid. Lipin-1
      mutations cause lipodystrophy in mice and acute myopathy in humans. It is heavily
      phosphorylated, and the yeast ortholog Pah1p becomes membrane-associated and
      active upon dephosphorylation by the Nem1p-Spo7p membrane complex. A mammalian
      ortholog of Nem1p is the C-terminal domain nuclear envelope phosphatase 1
      (CTDNEP1, formerly "dullard"), but its Spo7p-like partner is unknown, and the
      need for its existence is debated. Here, we identify the metazoan ortholog of
      Spo7p, TMEM188, renamed nuclear envelope phosphatase 1-regulatory subunit 1 (NEP1
      R1). CTDNEP1 and NEP1-R1 together complement a nem1Deltaspo7Delta strain to block
      endoplasmic reticulum proliferation and restore triacylglycerol levels and lipid
      droplet number. The two human orthologs are in a complex in cells, and the amount
      of CTDNEP1 is increased in the presence of NEP1-R1. In the Caenorhabditis elegans
      embryo, expression of nematode CTDNEP1 and NEP1-R1, as well as lipin-1, is
      required for normal nuclear membrane breakdown after zygote formation. The
      expression pattern of NEP1-R1 and CTDNEP1 in human and mouse tissues closely
      mirrors that of lipin-1. CTDNEP1 can dephosphorylate lipins-1a, -1b, and -2 in
      human cells only in the presence of NEP1-R1. The nuclear fraction of lipin-1b is
      increased when CTDNEP1 and NEP1-R1 are co-expressed. Therefore, NEP1-R1 is
      functionally conserved from yeast to humans and functions in the lipin activation
      pathway.

PMID- 22134923
TI  - Disruption of kv1.3 channel forward vesicular trafficking by hypoxia in human T
      lymphocytes.
AB  - Hypoxia in solid tumors contributes to decreased immunosurveillance via down
      regulation of Kv1.3 channels in T lymphocytes and associated T cell function
      inhibition. However, the mechanisms responsible for Kv1.3 down-regulation are not
      understood. We hypothesized that chronic hypoxia reduces Kv1.3 surface expression
      via alterations in membrane trafficking. Chronic hypoxia decreased Kv1.3 surface
      expression and current density in Jurkat T cells. Inhibition of either protein
      synthesis or degradation and endocytosis did not prevent this effect. Instead,
      blockade of clathrin-coated vesicle formation and forward trafficking prevented
      the Kv1.3 surface expression decrease in hypoxia. Confocal microscopy revealed an
      increased retention of Kv1.3 in the trans-Golgi during hypoxia. Expression of
      adaptor protein-1 (AP1), responsible for clathrin-coated vesicle formation at the
      trans-Golgi, was selectively down-regulated by hypoxia. Furthermore, AP1 down
      regulation increased Kv1.3 retention in the trans-Golgi and reduced Kv1.3
      currents. Our results indicate that hypoxia disrupts AP1/clathrin-mediated
      forward trafficking of Kv1.3 from the trans-Golgi to the plasma membrane thus
      contributing to decreased Kv1.3 surface expression in T lymphocytes.

PMID- 22134924
TI  - Recombinant cannabinoid type 2 receptor in liposome model activates g protein in
      response to anionic lipid constituents.
AB  - Human cannabinoid type 2 (CB(2)) receptor expressed in Escherichia coli was
      purified and successfully reconstituted in the functional form into lipid
      bilayers composed of POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1
      palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS), and cholesteryl
      hemisuccinate (CHS). Reconstitution was performed by detergent removal from the
      protein/lipid/detergent mixed micelles either on an adsorbent column, or by rapid
      dilution to below the critical micelle concentration of detergent followed by
      removal of detergent monomers on a concentrator. Proteoliposomes prepared at a
      protein/phospholipid/CHS molar ratio of 1/620-650/210-220 are free of detergent
      as shown by (1)H NMR, have a homogeneous protein/lipid ratio shown by isopycnic
      gradient ultracentrifugation, and are small in size with a mean diameter of 150
      200 nm as measured by dynamic light scattering. Functional integrity of the
      reconstituted receptor was confirmed by quantitative binding of (2)H-labeled
      agonist CP-55,940-d(6) measured by (2)H magic angle spinning NMR, as well as by
      activation of G protein. The efficiency of G protein activation by agonist-bound
      CB(2) receptor was affected by negative electric surface potentials of
      proteoliposomes controlled by the content of anionic CHS or POPS. The activation
      was highest at an anionic lipid content of about 50 mol %. There was no
      correlation between the efficiency of G protein activation and an increase of
      hydrocarbon chain order induced by CHS or cholesterol. The results suggest the
      importance of anionic lipids in regulating signal transduction by CB(2) receptor
      and other class A GPCR. The successful reconstitution of milligram quantities of
      pure, functional CB(2) receptor enables a wide variety of structural studies.

PMID- 22134926
TI  - Hand bradykinesia improved by DBS in the dorsal putamen?

PMID- 22134925
TI  - Polyglutamine expansion alters the dynamics and molecular architecture of
      aggregates in dentatorubropallidoluysian atrophy.
AB  - Preferential accumulation of mutant proteins in the nucleus has been suggested to
      be the molecular culprit that confers cellular toxicity in the neurodegenerative
      disorders caused by polyglutamine (polyQ) expansion. Here, we use dynamic imaging
      approaches, orthogonal cross-seeding, and composition analysis to examine the
      dynamics and structure of nuclear and cytoplasmic inclusions of atrophin-1,
      implicated in dentatorubropallidoluysian atrophy, a polyQ-based disease with
      complex clinical features. Our results reveal a large heterogeneity in the
      dynamics of the nuclear inclusions compared with the compact and immobile
      cytoplasmic aggregates. At least two types of inclusions of expanded atrophin-1
      with different mobility of the molecular species and ability to exchange with the
      surrounding monomer pool coexist in the nucleus. Intriguingly, the enrichment of
      nuclear inclusions with slow dynamics parallels changes in the aggregate core
      architecture that are dominated by the polyQ stretch. We propose that the
      observed complexity in the dynamics of the nuclear inclusions provides a
      molecular explanation for the enhanced cellular toxicity of the nuclear
      aggregates in polyQ-based neurodegeneration.

PMID- 22134927
TI  - hUbiquitome: a database of experimentally verified ubiquitination cascades in
      humans.
AB  - Protein ubiquitination is an evolutionarily conserved and functionally diverse
      post-translational modification achieved through the sequential action of E1
      activating enzymes, E2-conjugating enzymes and E3 ligases. A summary of validated
      ubiquitination substrates have been presented and a prediction of new substrates
      have been conducted in yeast. However, a systematic summary of human
      ubiquitination substrates containing experimental evidence and the enzymatic
      cascade of each substrate is not available. In the present study, hUbiquitome web
      resource is introduced, a public resource for the retrieval of experimentally
      verified human ubiquitination enzymes and substrates. hUbiquitome is the first
      comprehensive database of human ubiquitination cascades. Currently, hUbiquitome
      has in its repertoire curated data comprising 1 E1 enzyme, 12 E2 enzymes, 138 E3
      ligases or complexes, 279 different substrate proteins and 17 deubiquitination
      enzyme terms. The biological functions of substrates from different kinds of E3s
      were analyzed using the collected data. The findings show that substrates
      ubiquitinated by RING (Really Interesting New Gene) E3s are enriched most in
      apoptosis-related processes, whereas substrates ubiquitinated by other E3s are
      enriched in gene expression-associated processes. An analysis of the data
      demonstrates the biological process preferences of the different kinds of E3s.
      hUbiquitome is the first database to systematically collect experimentally
      validated ubiquitinated proteins and related ubiquitination cascade enzymes which
      might be helpful in the field of ubiquitination-modification research. Database
      URL: http://202.38.126.151/hmdd/hubi/

PMID- 22134928
TI  - Methods to examine tight junction physiology in cancer stem cells: TEER,
      paracellular permeability, and dilution potential measurements.
AB  - Our understanding of the essential role played by cancer stem cells or tumor
      initiating cells in epithelial cell-derived tumor types is rapidly advancing.
      Nevertheless, the identification and characterization of these cells pose a
      considerable challenge. Among changes in the epithelium in oncogenesis are
      changes in the permeability barrier, a phenotypic trait based on tight junction
      formation and function. Tight junctions regulate the movement of solutes, ions
      and water across the paracellular space. On a cellular level, they maintain cell
      polarity by limiting the lateral diffusion of membrane components. Depending on
      the type of epithelial tissue, the barrier characteristics with respect to
      electrical resistance, size and ion charge selectivity vary quite significantly.
      Thus, elucidating changes in expression of Claudins, an essential component of
      tight junctions, has become a very active area of investigation in oncogenesis.
      This chapter provides detailed protocols on how to quantify three aspects of
      tight junction physiology using in vitro cell culture systems that are
      particularly applicable to analysis and comparison of cancer stem cells and their
      normal counterparts.

PMID- 22134930
TI  - The end of an era in mayo clinic proceedings' publishing practices.

PMID- 22134929
TI  - DNA methyltransferases1 (DNMT1) and 3a (DNMT3a) colocalize with GAD67-positive
      neurons in the GAD67-GFP mouse brain.
AB  - DNA methylation is an epigenetic regulatory mechanism commonly associated with
      transcriptional silencing. DNA methyltransferases (DNMTs) are a family of related
      proteins that both catalyze the de novo formation of 5-methylcytosine and
      maintain these methylation marks in cell-specific patterns in virtually all
      mitotic cells of the body. In the adult brain, methylation occurs in progenitor
      cells of the neurogenic zones and in postmitotic neurons. Of the DNMTs, DNMT1 and
      DNMT3a are most highly expressed in postmitotic neurons. While it has been
      commonly thought all postmitotic neurons and glia express DNMTs at comparable
      levels, the coexpression of selected DNMTs with markers of distinct
      neurotransmitter phenotypes has not been previously examined in detail in the
      mouse. To this end, we analyzed the expression of DNMT1 and DNMT3a along with
      GAD67 in the brains of the glutamic acid decarboxylase67-enhanced green
      fluorescent protein (GAD67-GFP) knockin mice. After first confirming that GFP
      immunopositive neurons were also GAD67-positive, we showed that in the motor
      cortex, piriform cortex, striatum, CA1 region of the hippocampus, dentate gyrus,
      and basolateral amygdala (BLA), GFP immunofluorescence coincided with the signal
      corresponding to DNMT1 and DNMT3a. A detailed examination of cortical neurons,
      showed that ~30% of NeuN-immunopositive neurons were also DNMT1-positive. These
      data do not exclude the expression of DNMT1 or DNMT3a in glutamatergic neurons
      and glia. However, they suggest that their expression is low compared with the
      levels present in GABAergic neurons.

PMID- 22134931
TI  - Post-shingles neuralgia by any definition is painful, but is it PHN?

PMID- 22134932
TI  - Natriuretic peptides as markers of cardiovascular risk: the story continues.

PMID- 22134933
TI  - Predictive utility of atrial, N-terminal pro-atrial, and N-terminal pro-B-type
      natriuretic peptides for mortality and cardiovascular events in the general
      community: a 9-year follow-up study.
AB  - OBJECTIVE: To determine the predictive value of atrial natriuretic peptide (ANP),
      N-terminal pro-ANP (NT-proANP), and N-terminal pro-B-type natriuretic peptide (NT
      proBNP) for mortality and cardiovascular events in the general population in the
      absence of overt heart failure (HF). PARTICIPANTS AND METHODS: We identified a
      community-based cohort of 2042 individuals. Those with stage C or D HF (n=45) and
      renal insufficiency (n=6) were excluded from the current study. Of the remaining
      individuals, 1769 (89%) underwent echocardiography and measurement of plasma ANP,
      NT-proANP, and NT-proBNP. Participants were followed up from January 1, 1997, to
      May 1, 2009, for mortality, HF, myocardial infarction (MI), and cerebrovascular
      accident; median follow-up was 9 years. RESULTS: After adjustment for
      conventional clinical risk factors, NT-proANP had significant predictive value
      for mortality but not for HF, MI, or cerebrovascular accident, whereas ANP lacked
      any predictive value. The predictive value of NT-proANP for mortality was
      attenuated after adjustment for structural and functional cardiac abnormalities.
      In contrast, NT-proBNP had predictive value for mortality, HF, and MI after
      adjustment for conventional risk factors and retained significance for mortality
      and HF after adjustment for structural and functional cardiac abnormalities.
      CONCLUSION: Our results suggest that NT-proBNP is a more robust cardiac biomarker
      compared with ANP or NT-proANP and is independently predictive of mortality and
      HF in the general population free of overt HF.

PMID- 22134934
TI  - Medication errors in patients with severe chronic kidney disease and acute
      coronary syndrome: the impact of computer-assisted decision support.
AB  - OBJECTIVE: To evaluate the impact of computerized physician order entry (CPOE)
      with decision support on the frequency of antithrombotic medication errors in
      patients with chronic kidney disease (CKD) admitted with acute coronary syndrome
      (ACS) and to measure what effect it would have on in-hospital bleeding. PATIENTS
      AND METHODS: We evaluated 80 patients with CKD who were admitted with ACS between
      January 1, 2009, and December 31, 2010, using either a standardized order set or
      CPOE with decision support to assess the frequency of medication errors and in
      hospital bleeding. RESULTS: Of the 80 patients, 47 were admitted with standard
      orders vs 33 with CPOE. In-hospital bleeding occurred in 13 patients: 10 in the
      standard orders group vs 3 in the CPOE group (P=.12). In-hospital bleeding
      occurred in 5 (63%) of 8 patients receiving a contraindicated antithrombotic
      medication compared with 8 (11%) of 72 patients receiving appropriate medications
      (P=.002); the corresponding length of stay was 12.0 days compared with 6.8 days
      (P=.10). Contraindicated medications were given to no patients in the CPOE group
      vs 8 patients (17%) in the standard orders group (P=.01). CONCLUSION: Medication
      errors occur frequently in patients with CKD admitted with ACS and result in a
      high risk of in-hospital bleeding. Use of CPOE with decision support is feasible
      in the ACS setting and may lead to improved patient safety.

PMID- 22134935
TI  - The association between renal atherosclerotic plaque characteristics and renal
      function before and after renal artery intervention.
AB  - OBJECTIVE: To evaluate the effect of plaque composition on renal function after
      renal artery intervention (RAI). PATIENTS AND METHODS: In 33 consecutive patients
      with atherosclerotic renal artery stenosis (enrolled between January 1, 2007, and
      April 30, 2009), renal angiography, pressure gradients across the lesion, and
      intravascular ultrasonography (IVUS) with virtual histology (VH)-derived plaque
      characteristics were assessed. In 25 patients who underwent RAI, estimated
      glomerular filtration rate (eGFR) was evaluated at baseline and at 3 months.
      RESULTS: Mean pressure gradients across the lesion were poorly associated with
      baseline eGFR (r=-0.37; P=.07). In gray scale IVUS data, only remodeling index
      was significantly correlated with baseline eGFR (r=-0.38; P=.03). Plaque
      components classified by VH-IVUS had no correlation with baseline eGFR. During
      follow-up of 25 patients, the improvement in eGFR after RAI was observed in 9
      patients, unchanged in 3, and deteriorated in 13. Overall, follow-up eGFR
      (median, 49.0 mL/min/1.73 m(2); interquartile range [IQR], 40.6-63.9 mL/min/1.73
      m(2)) was unchanged compared with baseline eGFR (median, 53.8 mL/min/1.73 m(2);
      IQR, 41.4-63.4 mL/min/1.73 m(2); P=.38). The percent change in eGFR (median, 
      0.2%; IQR, -16.0% to 16.0%) after RAI had a significant negative correlation with
      the mean percentage of necrotic core classified by VH-IVUS (r=-0.47; P=.02), and
      the mean percentage of necrotic core was significantly larger in patients with
      deterioration of eGFR than in patients without deterioration of eGFR (median,
      12.7%; IQR, 9.5%-19.5%; vs median, 8.3%; IQR, 5.5%-11.6%; P=.04). CONCLUSION: In
      patients with atherosclerotic renal artery stenosis, the change in eGFR after RAI
      was related to plaque composition classified by VH-IVUS. The evaluation of plaque
      composition may provide more insights into the change in renal function after
      RAI.

PMID- 22134937
TI  - Detecting delayed microbiology results after hospital discharge: improving
      patient safety through an automated medical informatics tool.
AB  - We developed a computerized medical informatics tool to identify patients who had
      a culture performed on a sterile body site specimen during their hospitalization
      that subsequently turned positive after hospital dismissal. During a 13-month
      period, 533 patients had a positive culture identified by our Computer-Based
      Antimicrobial Monitoring (CBAM) program after hospital dismissal, and 112 (21%)
      of these culture results necessitated an intervention and communication with the
      primary health care professional. Thirty-two (29%) of positive cultures were from
      the blood. Thirty-eight (34%) of the CBAM interventions with available outcome
      data resulted in initiation of, change in, or prolongation of outpatient
      antimicrobial therapy. The CBAM program serves an important role in optimizing
      patient care and communication with the health care professional during the
      transition from inpatient to outpatient management.

PMID- 22134936
TI  - Population screening for barrett esophagus: a prospective randomized pilot study.
AB  - OBJECTIVE: To assess the feasibility of unsedated transnasal endoscopy (uTNE) and
      video capsule endoscopy (VCE) as alternatives to sedated endoscopy (sEGD) as
      screening tools for Barrett esophagus (BE) and to obtain preliminary estimates of
      participation rates for sEGD, uTNE, and VCE when used for community BE screening
      in a population cohort. PATIENTS AND METHODS: From February 1, 2009, to May 31,
      2010, patients from Olmsted County, Minnesota, who were older than 50 years and
      had no history of known BE were randomized (stratified by age, sex, reflux
      symptoms noted in a validated questionnaire) into 3 groups for esophageal
      evaluation with sEGD, uTNE, or VCE. Participation rates and safety profiles were
      estimated. RESULTS: We contacted 127 patients to recruit 20 for each procedure
      arm (60 total). The probability of participation was 38% (95% confidence interval
      [CI], 26%-51%) for sEGD, 50% (95% CI, 35%-65%) for uTNE, and 59% (95% CI, 42%
      74%) for VCE. Both uTNE and VCE were well tolerated without adverse effects. BE
      was identified in 3 patients and esophagitis in 8. CONCLUSION: Unsedated
      techniques may be acceptable, feasible, and safe alternatives to sEGD to screen
      for BE in the community. TRIAL REGISTRATION: clinicaltrials.gov identifier:
      NCT00943280.

PMID- 22134938
TI  - Medicine and the media: balancing the public's right to know with the privacy of
      the patient.

PMID- 22134940
TI  - Cheaper, simpler, and better: tips for treating seniors with Parkinson disease.
AB  - Treatment of seniors with Parkinson disease is within the domain of primary care
      physicians and internists. A good working knowledge of carbidopa/levodopa
      principles should allow excellent care of most patients, at least during the
      early years of the disease. Even later, when levodopa responses become more
      complicated (eg, dyskinesias, motor fluctuations, insomnia, anxiety), levodopa
      adjustments may be all that is necessary. A dozen tips for optimizing treatment
      of Parkinson disease are discussed herein.

PMID- 22134939
TI  - Rethinking cocaine-associated chest pain and acute coronary syndromes.
AB  - Every year more than 500,000 patients present to the emergency department with
      cocaine-associated complications, most commonly chest pain. Many of these
      patients undergo extensive work-up and treatment. Much of the evidence regarding
      cocaine's cardiovascular effects, as well as the current management of cocaine
      associated chest pain and acute coronary syndromes, is anecdotally derived and
      based on studies written more than 2 decades ago that involved only a few
      patients. Newer studies have brought into question many of the commonly held
      theories and practices regarding the etiology, diagnosis, and treatment of this
      common clinical scenario. However, there continues to be a paucity of
      prospective, randomized trials addressing this topic as it relates to clinical
      outcomes. We searched PubMed for English-language articles from 1960 to 2011
      using the keywords cocaine, chest pain, coronary arteries, myocardial infarction,
      emergency department, cardiac biomarkers, electrocardiogram, coronary computed
      tomography, observation unit, beta-blockers, benzodiazepines, nitroglycerin,
      calcium channel blockers, phentolamine, and cardiomyopathy; including various
      combinations of these terms. We reviewed the abstracts to confirm relevance, and
      then full articles were extracted. References from extracted articles were also
      reviewed for relevant articles. In this review, we critically evaluate the
      limited historical evidence underlying the current teachings on cocaine's
      cardiovascular effects and management of cocaine-associated chest pain. We aim to
      update the reader on more recent, albeit small, studies on the emergency
      department evaluation and clinical and pharmacologic management of cocaine
      associated chest pain. Finally, we summarize recent guidelines and review an
      algorithm based on the current best evidence.

PMID- 22134941
TI  - 69-year-old woman with dyspnea and cough productive of white sputum.

PMID- 22134944
TI  - The "spiked helmet" sign: a new electrocardiographic marker of critical illness
      and high risk of death.

PMID- 22134943
TI  - Nitrofurantoin: preferred empiric therapy for community-acquired lower urinary
      tract infections.

PMID- 22134942
TI  - Current concepts in antimicrobial therapy against select gram-positive organisms:
      methicillin-resistant Staphylococcus aureus, penicillin-resistant pneumococci,
      and vancomycin-resistant enterococci.
AB  - Gram-positive bacteria cause a broad spectrum of disease in immunocompetent and
      immunocompromised hosts. Despite increasing knowledge about resistance
      transmission patterns and new antibiotics, these organisms continue to cause
      significant morbidity and mortality, especially in the health care setting.
      Methicillin-resistant Staphylococcus aureus poses major problems worldwide as a
      cause of nosocomial infection and has emerged as a cause of community-acquired
      infections. This change in epidemiology affects choices of empirical antibiotics
      for skin and skin-structure infections and community-acquired pneumonia in many
      settings. Throughout the world, the treatment of community-acquired pneumonia and
      other respiratory tract infections caused by penicillin-resistant Streptococcus
      pneumoniae has been complicated by resistance to beta-lactam and macrolide
      antibacterial drugs. Vancomycin-resistant enterococci are a major cause of
      infection in the hospital setting and remain resistant to treatment with most
      standard antibiotics. Treatment of diseases caused by resistant gram-positive
      bacteria requires appropriate use of available antibiotics and stewardship to
      prolong their effectiveness. In addition, appropriate and aggressive infection
      control efforts are vital to help prevent the spread of resistant pathogens.

PMID- 22134945
TI  - Gaining insights into chronic natural killer cell leukemias through extensive
      characterization of an individual case.

PMID- 22134946
TI  - Impressive vascular compression of the trigeminal nerve.

PMID- 22134947
TI  - Differential expression of occludin in patients with ulcerative colitis and
      healthy controls.

PMID- 22134948
TI  - Bioluminescence imaging of energy depletion in vascular pathology: patent ductus
      arteriosus and atherosclerosis.
AB  - The artery wall may develop energy depletion due to insufficient nutritional
      supply. However, until recently it has not been possible to validate this
      hypothesis because no available technology has allowed assessment of energy
      metabolism with sufficient spatial resolution. We use high resolution
      bioluminescence metabolic imaging to study energy metabolism in two
      mechanistically different vascular pathologies: patent ductus arteriosus and
      atherosclerosis. Physiological energy depletion in postnatally constricting
      ductus arteriosus promotes permanent closure. Insufficient ductus energy
      depletion, common in preterm infants, is associated with persistent patent ductus
      arteriosus, a condition with significantly increased morbidity and mortality. In
      contrast, in atherosclerosis, energy depletion in the macrophage-rich lesion core
      promotes cell death contributing to lesion instability and disease progression.

PMID- 22134949
TI  - Enantioselective copper-catalyzed conjugate addition of trimethylaluminium to
      beta,gamma-unsaturated alpha-ketoesters.

PMID- 22134950
TI  - Procyanidins from grape pomace are suitable inhibitors of human endothelial NADPH
      oxidase.
AB  - Procyanidins have been associated with a reduced risk of cardiovascular diseases
      such as atherosclerosis. However, the molecular mechanisms underlying this
      benefit are not fully understood. Increased reactive oxygen species (ROS)
      production generated by nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase is a common problem in different cardiovascular diseases. Our objective
      was to evaluate the effects of procyanidin-rich fractions from distilled grape
      pomace on NADPH oxidase activity in human umbilical vein endothelial cells
      (HUVEC). Three differently polymerized and galloylated procyanidin fractions were
      analyzed for their NADPH oxidase inhibitory activity in cell lysates and in HUVEC
      cultures. All of the three fractions, up to 1 ug/ml, equally inhibited isolated
      NADPH oxidase in HUVEC lysates in a concentration-dependent manner and
      independently of any superoxide anion scavenging activities. The procyanidin
      fractions even blocked NADPH oxidase activity in intact HUVEC, inhibiting ROS
      production at both extra- and intracellular levels. The fractions achieved the
      same effects that known NADPH oxidase inhibitors, such as diphenylene iodonium
      and apocynin, but they presented better hydrosolubility. Our results demonstrated
      that procyanidin from grape pomace inhibit human endothelial NADPH oxidase
      regardless of their polymerization degree and galloylation percentage. Therefore,
      procyanidins are suitable NADPH oxidase inhibitors which could serve as models
      for therapeutic alternatives for cardiovascular diseases.

PMID- 22134951
TI  - Dietary folate, but not choline, modifies neural tube defect risk in Shmt1
      knockout mice.
AB  - BACKGROUND: Low dietary choline intake has been proposed to increase the risk of
      neural tube defects (NTDs) in human populations. Mice with reduced Shmt1
      expression exhibit a higher frequency of NTDs when placed on a folate- and
      choline-deficient diet and may represent a model of human NTDs. The individual
      contribution of dietary folate and choline deficiency to NTD incidence in this
      mouse model is not known. OBJECTIVE: To dissociate the effects of dietary folate
      and choline deficiency on Shmt1-related NTD sensitivity, we determined NTD
      incidence in embryos from Shmt1-null dams fed diets deficient in either folate or
      choline. DESIGN: Shmt1(+/+) and Shmt1(-/-) dams were maintained on a standard
      AIN93G diet (Dyets), an AIN93G diet lacking folate (FD), or an AIN93G diet
      lacking choline (CD). Virgin Shmt1(+/+) and Shmt1(-/-) dams were crossed with
      Shmt1(+/-) males, and embryos were examined for the presence of NTDs at embryonic
      day (E) 11.5 or E12.5. RESULTS: Exencephaly was observed only in Shmt1(-/-)
      embryos isolated from dams maintained on the FD diet (P = 0.004). Approximately
      33% of Shmt1(-/-)embryos (n = 18) isolated from dams maintained on the FD diet
      exhibited exencephaly. NTDs were not observed in any embryos isolated from dams
      maintained on the CD (n = 100) or control (n = 152) diets or in any Shmt1(+/+) (n
      = 78) or Shmt1(+/-) embryos (n = 182). CONCLUSION: Maternal folate deficiency
      alone is sufficient to induce NTDs in response to embryonic Shmt1 disruption.

PMID- 22134952
TI  - Dual-energy X-ray absorptiometry-based body volume measurement for 4-compartment
      body composition.
AB  - BACKGROUND: Total body volume (TBV), with the exclusion of internal air voids, is
      necessary to quantify body composition in Lohman's 4-compartment (4C) model.
      OBJECTIVE: This investigation sought to derive a novel, TBV measure with the use
      of only dual-energy X-ray absorptiometry (DXA) attenuation values for use in
      Lohman's 4C body composition model. DESIGN: Pixel-specific masses and volumes
      were calculated from low- and high-energy attenuation values with the use of
      first principle conversions of mass attenuation coefficients. Pixel masses and
      volumes were summed to derive body mass and total body volume. As proof of
      concept, 11 participants were recruited to have 4C measures taken: DXA, air
      displacement plethysmography (ADP), and total body water (TBW). TBV measures with
      the use of only DXA (DXA-volume) and ADP-volume measures were compared for each
      participant. To see how body composition estimates were affected by these 2
      methods, we used Lohman's 4C model to quantify percentage fat measures for each
      participant and compared them with conventional DXA measures. RESULTS: DXA-volume
      and ADP-volume measures were highly correlated (R(2) = 0.99) and showed no
      statistically significant bias. Percentage fat by DXA volume was highly
      correlated with ADP-volume percentage fat measures and DXA software-reported
      percentage fat measures (R(2) = 0.96 and R(2) = 0.98, respectively) but were
      slightly biased. CONCLUSIONS: A novel method to calculate TBV with the use of a
      clinical DXA system was developed, compared against ADP as proof of principle,
      and used in Lohman's 4C body composition model. The DXA-volume approach
      eliminates many of the inherent inaccuracies associated with displacement
      measures for volume and, if validated in larger groups of participants, would
      simplify the acquisition of 4C body composition to a single DXA scan and TBW
      measure.

PMID- 22134953
TI  - Novel functional conjugative hyperbranched polymers with aggregation-induced
      emission: synthesis through one-pot "A2+B4" polymerization and application as
      explosive chemsensors and PLEDs.
AB  - With the aim to develop new tetraphenylethylene (TPE)-based conjugated
      hyperbranched polymer, TPE units, one famous aggregation-induced emission (AIE)
      active group, are utilized to construct hyperbranched polymers with three other
      aromatic blocks, through an "A2+B4" approach by using one-pot Suzuki
      polycondensation reaction. These three hyperbranched polymers exhibit interesting
      AIEE behavior and act as explosive chemsensors with high sensitivity both in the
      nanoparticles and solid states. This is the first report of the AIE activity of
      the TPE-based conjugated hyperbranched polymers. Their corresponding PLED devices
      also demonstrate good performance. 

PMID- 22134954
TI  - Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating
      Scale.
AB  - Impulse control disorders and related disorders (hobbyism-punding and dopamine
      dysregulation syndrome) occur in 15% to 20% of Parkinson's disease (PD) patients.
      We assessed the validity and reliability of the Questionnaire for Impulsive
      Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS), a rating
      scale designed to measure severity of symptoms and support a diagnosis of impulse
      control disorders and related disorders in PD. A convenience sample of PD
      patients at a movement disorders clinic self-completed the QUIP-RS and were
      administered a semistructured diagnostic interview by a blinded trained rater to
      assess discriminant validity for impulse control disorders (n = 104) and related
      disorders (n = 77). Subsets of patients were assessed to determine interrater
      reliability (n = 104), retest reliability (n = 63), and responsiveness to change
      (n = 29). Adequate cutoff points (both sensitivity and specificity values >80%
      plus acceptable likelihood ratios) were established for each impulse control
      disorder and hobbyism-punding. Interrater and retest reliability (intraclass
      correlation coefficient r) were >0.60 for all disorders. Participants in an
      impulse control disorder treatment study who experienced full (t = 3.65, P =
      .004) or partial (t = 2.98, P = .01) response demonstrated significant
      improvement on the rating scale over time, while nonresponders did not (t = 0.12,
      P = .91). The QUIP-RS appears to be valid and reliable as a rating scale for
      impulse control disorders and related disorders in PD. Preliminary results
      suggest that it can be used to support a diagnosis of these disorders, as well as
      to monitor changes in symptom severity over time.

PMID- 22134955
TI  - Estimating underreported N2 disease in rectal cancer patients with low lymph node
      counts.
AB  - BACKGROUND: The variability in the number of lymph nodes examined needs to be
      taken into account for adequate staging. The definition of nodal staging was
      refined by quantifying the likelihood of N2 disease when the patient had fewer
      than four positive LN. METHODS: In a retrospective study a total of 548 patients
      with node positive rectal cancer and curative surgery between 1990 and 2006 were
      identified. The misclassification of pN staging was estimated with a Bayesian
      computation. The prognostic value of the calculated probability, lymph node ratio
      (LNR), and nodal stage was assessed with Cox proportional hazard regression.
      RESULTS: A probability of understaging of 40% or more indicated worse prognosis
      of cancer-specific survival (CSS) with hazard ratio 2.6 (95%CI: 1.8-3.9, P <
      0.001). The concordance index of a multivariate model with probability of N2
      disease as a prognostic factor for survival was 0.68 for all patients and 0.75
      for patients with less than 10 lymph nodes examined. CONCLUSION: Utilizing
      estimated probabilities of N2 disease improves our ability to predict survival,
      in particular in patients with low LN count. These probabilities allow for a
      simple rule in patient counseling and clinical decision making.

PMID- 22134957
TI  - Prolonged exposure therapy: past, present, and future.

PMID- 22134958
TI  - Relationship between FKBP5 polymorphisms and depression symptoms among kidney
      transplant recipients.
AB  - BACKGROUND: Several polymorphisms in FK506 Binding Protein gene (FKBP5) and a
      history of child abuse have been shown to be associated with an increased risk
      for posttraumatic stress disorder (PTSD). It has also been demonstrated that the
      same polymorphisms of FKBP5 are associated with increased recurrence of
      depressive episodes and rapid response to antidepressant treatment. However,
      there are only limited numbers of studies replicating the polymorphisms as
      vulnerability factors for the development of mental illnesses, such as PTSD and
      depression after stressful life event, especially with a specific incidence, such
      as kidney transplant surgery. METHODS: A retrospective analysis was conducted
      using the electronic medical records of 131 adult kidney transplant recipients.
      Depression severity after kidney transplantation was measured by PHQ-9, and
      stored blood was genotyped for variants in the Serotonin Transporter (SLC6A4),
      Brain-Derived Neurotrophic Factor, Catecholamine-O-Methyltransferase,
      Corticotropin-Releasing Hormone Receptor, and FKBP5 genes. Spearman correlations
      were used to test for association between genetic variants and depression
      severity. RESULTS: The rare alleles at three out of four SNPs in FKBP5
      (rs1360780, rs9296158, and rs9470080) were associated with increased PHQ-9 scores
      (P<.05), whereas the last FKBP5 SNP (rs3800373) showed a trend of association
      (P<.10). All four FKBP5 SNPs are in strong linkage disequilibrium. Although in a
      subgroup of Caucasian non-Hispanic subjects the association was not statistically
      significant, the direction of association was consistent with that observed in
      the entire sample as well as in previous studies. Polymorphisms in genes other
      than FKBP5 were not associated with PHQ-9 scores. CONCLUSIONS: Polymorphisms in
      FKBP5 may be associated with higher depression scores in kidney transplant
      recipients.

PMID- 22134956
TI  - Umbilical cord blood immunology: relevance to stem cell transplantation.
AB  - Because of its easier accessibility and less severe graft-versus-host disease,
      umbilical cord blood (UCB) has been increasingly used as an alternative to bone
      marrow for hematopoietic stem cell transplantation. Naivete of UCB lymphocytes,
      however, results in delayed immune reconstitution and infection-related mortality
      in transplant recipients. This review updates the phenotypic and functional
      deficiencies of various immune cell populations in UCB compared with their adult
      counterparts and discusses clinical implications and possible therapeutic
      strategies to improve the outcome of stem cell transplantation.

PMID- 22134959
TI  - Dissociative disorders in DSM-5.
AB  - BACKGROUND: We present recommendations for revision of the diagnostic criteria
      for the Dissociative Disorders (DDs) for DSM-5. The periodic revision of the DSM
      provides an opportunity to revisit the assumptions underlying specific diagnoses
      and the empirical support, or lack of it, for the defining diagnostic criteria.
      METHODS: This paper reviews clinical, phenomenological, epidemiological,
      cultural, and neurobiological data related to the DDs in order to generate an up
      to-date, evidence-based set of DD diagnoses and diagnostic criteria for DSM-5.
      First, we review the definitions of dissociation and the differences between the
      definitions of dissociation and conceptualization of DDs in the DSM-IV-TR and the
      ICD-10, respectively. Also, we review more general conceptual issues in defining
      dissociation and dissociative disorders. Based on this review, we propose a
      revised definition of dissociation for DSM-5 and discuss the implications of this
      definition for understanding dissociative symptoms and disorders. RESULTS: We
      make the following recommendations for DSM-5: 1. Depersonalization Disorder (DPD)
      should include derealization symptoms as well. 2. Dissociative Fugue should
      become a subtype of Dissociative Amnesia (DA). 3. The diagnostic criteria for DID
      should be changed to emphasize the disruptive nature of the dissociation and
      amnesia for everyday as well as traumatic events. The experience of possession
      should be included in the definition of identity disruption. 4. Dissociative
      Trance Disorder should be included in the Unspecified Dissociative Disorder (UDD)
      category. CONCLUSIONS: There is a growing body of evidence linking the
      dissociative disorders to a trauma history, and to specific neural mechanisms.

PMID- 22134960
TI  - Role of the transcription factor Sp1 in regulating the expression of the murine
      cathepsin E gene.
AB  - Cathepsin E (CE) is an intracellular aspartic proteinase that is exclusively
      expressed in cells of the gastrointestinal tracts, lymphoid tissues, urinary
      organs and red blood cells. However, the molecular mechanism by which CE is
      predominantly expressed in these cells remains unknown. Here, we report the
      identification of several transcription start sites of the CE gene and their
      regulatory factors in gastric adenosarcoma cells. We first identified several
      unique transcription start sites in mouse CE genes by an oligo cap method. Their
      analysis also revealed the existence of a non-coding region ~24-kb upstream of
      exon 1 in the CE gene and also the existence of two transcripts for CE.
      Luciferase analyses in upstream of exon 1 revealed that this site contained
      putative binding regions for the transcription factors Sp1, AP-1 and cEts-1
      essential for the expression of CE gene. Moreover, electrophoretic mobility shift
      assays revealed that the protein-oligonucleotides complex of the Sp1 site were
      supershifted by an anti-Sp1 antibody. The chromatin immunoprecipitation assay
      showed that Sp1 bound to the CE promoter region. In addition, overexpression of
      the Sp1 protein increased the expression of the CE protein. Altogether, these
      results suggest that Sp1 binding plays a particularly important role in the
      regulation of CE gene expression.

PMID- 22134961
TI  - Prior psychiatric hospitalization is associated with excess mortality in patients
      hospitalized with non-cardiac chest pain: a data linkage study based on the full
      Scottish population (1991-2006).
AB  - AIMS: Non-cardiac chest pain (NCCP) is considered a benign condition. We
      investigate case-fatality following an incident hospitalization for NCCP and
      determine whether previous psychiatric hospitalization is associated with short
      term mortality. METHODS AND RESULTS: This was a population-based retrospective
      cohort study of 159 888 patients discharged from hospital in Scotland (1991-2006)
      following a first NCCP hospitalization, using routinely collected morbidity and
      mortality data. All-cause and cardiovascular disease (CVD) mortality at 1 year
      following hospitalization was examined. A total of 3514 (4.4%) men and 3136
      (3.9%) women with a first NCCP hospitalization had a psychiatric hospitalization
      in the 10 years preceding incident NCCP hospitalization. Those with a previous
      psychiatric hospitalization were younger and more socioeconomically deprived
      (SED). Overall, crude case fatality at 1 year was 4.4% in men and 3.7% in women.
      This was higher in patients with a previous psychiatric hospitalization compared
      with those without (overall: men 6.3 vs. 4.3%; women: 5.3 vs. 3.6%), in all age
      groups and all SED quintiles. Following adjustment (year of NCCP hospitalization,
      SED, co-morbid diabetes, and hypertension), the hazard of all-cause and CVD
      specific death at 1 year was higher in men and women with a previous psychiatric
      hospitalization than without, with effect modification according to age group.
      CONCLUSION: Non-cardiac chest pain is not an entirely benign condition.
      Individuals with a hospital discharge diagnosis of NCCP who have a previous
      psychiatric hospitalization have a greater risk of death, all-cause, and CVD
      specific, at 1 year, than those without. A NCCP hospitalization is an opportunity
      to engage, and where appropriate, intervene to modify cardiovascular risk in this
      difficult-to-reach and high-risk group.

PMID- 22134962
TI  - Increased cardiovascular risk associated with non-cardiac chest pain in patients
      with a prior psychiatric hospitalization: an opportunity and challenge for both
      the psychiatrist and the cardiologist.

PMID- 22134963
TI  - Legal and definitional issues affecting the identification and education of
      adults with specific learning disabilities in adult education programs.
AB  - Although the exact prevalence is not determined, a noticeable subset of
      individuals who enroll in adult education and training programs have either
      diagnosed or undiagnosed specific learning disabilities (SLD). Understanding SLD
      is important basic information for adult educators to inform program policies as
      well as determine effective instructional practices. This article discusses the
      development of definitions of SLD and current agreement on the nature of SLD
      relevant to working with adults. It concludes with implications for adult
      education programs.

PMID- 22134964
TI  - Private speech use in arithmetical calculation: contributory role of phonological
      awareness in children with and without mathematical difficulties.
AB  - The majority of recent studies conclude that children's private speech
      development (private speech internalization) is related to and important for
      mathematical development and disabilities. It is far from clear, however, whether
      private speech internalization itself plays any causal role in the development of
      mathematical competence. The main concerns of the present study were whether
      phonological awareness skills relate to private speech internalization, and
      whether the answer to this question changes with children's age and mathematical
      achievement levels. Comparisons were made between 67 children diagnosed with math
      difficulties and 67 children without math difficulties from Grade 2 to Grade 7 in
      primary schools. Two separate laboratory investigations were performed to explore
      children's developmental levels of private speech and phonological awareness,
      respectively. Analysis was based on private speech differences, phonological
      awareness differences, and differences in occurrence of private
      speech/phonological-awareness category combinations. Children without math
      difficulties showed a grade-determined shift from less to more internalized
      private speech and from lower to higher levels of phonological awareness. In
      contrast, the development of children with math difficulties seemed almost to
      stop at the inaudible private speech/low level of phonological awareness
      combinations. Silence/high phonological level was the primary alternative for
      typical math achievers. Results are discussed in terms of directions for future
      research.

PMID- 22134965
TI  - Should we treat lower urinary tract symptoms without a definitive diagnosis? Yes.

PMID- 22134966
TI  - Should we treat lower urinary tract symptoms without a definitive diagnosis? No.

PMID- 22134967
TI  - Effectiveness of strategies incorporating training and support of traditional
      birth attendants on perinatal and maternal mortality: meta-analysis.
AB  - OBJECTIVE: To assess the effectiveness of strategies incorporating training and
      support of traditional birth attendants on the outcomes of perinatal, neonatal,
      and maternal death in developing countries. DESIGN: Systematic review with meta
      analysis. DATA SOURCES: Medline, Embase, the Allied and Complementary Medicine
      database, British Nursing Index, Cochrane Library, Cumulative Index to Nursing
      and Allied Health Literature, BioMed Central, PsycINFO, Latin American and
      Caribbean Health Sciences Literature database, African Index Medicus, Web of
      Science, Reproductive Health Library, and Science Citation Index (from inception
      to April 2011), without language restrictions. Search terms were "birth attend*",
      "traditional midwife", "lay birth attendant", "dais", and "comadronas".  Review
      methods We selected randomised and non-randomised controlled studies with
      outcomes of perinatal, neonatal, and maternal mortality. Two independent
      reviewers undertook data extraction. We pooled relative risks separately for the
      randomised and non-randomised controlled studies, using a random effects model.
      RESULTS: We identified six cluster randomised controlled trials (n=138 549) and
      seven non-randomised controlled studies (n=72 225) that investigated strategies
      incorporating training and support of traditional birth attendants. All six
      randomised controlled trials found a reduction in adverse perinatal outcomes; our
      meta-analysis showed significant reductions in perinatal death (relative risk
      0.76, 95% confidence interval 0.64 to 0.88, P<0.001; number needed to treat 35,
      24 to 70) and neonatal death (0.79, 0.69 to 0.88, P<0.001; 98, 66 to 170). Meta
      analysis of the non-randomised studies also showed a significant reduction in
      perinatal mortality (0.70, 0.57 to 0.84, p<0.001; 48, 32 to 96) and neonatal
      mortality (0.61, 0.48 to 0.75, P<0.001; 96, 65 to 168). Six studies reported on
      maternal mortality and our meta-analysis showed a non-significant reduction
      (three randomised trials, relative risk 0.79, 0.53 to 1.05, P=0.12; three non
      randomised studies, 0.80, 0.44 to 1.15, P=0.26). CONCLUSION: Perinatal and
      neonatal deaths are significantly reduced with strategies incorporating training
      and support of traditional birth attendants.

PMID- 22134968
TI  - How clinical and research failures lead to suboptimal prescribing: the example of
      chronic gout.

PMID- 22134969
TI  - Paralysed man asks High Court to allow doctors to end his life.

PMID- 22134970
TI  - Nitrogen-doped carbon nanotubes as a highly active metal-free catalyst for
      selective oxidation.
AB  - Catalytic reactions are generally carried out on supported metals or oxides,
      which act as an active phase and require impregnation and thermal treatment
      steps. During tests, the metal or oxide nanoparticles could be further sintered,
      which would induces deactivation. Direct incorporation of the active phase into
      the matrix of a support could be an elegant alternative to prevent catalyst
      deactivation. Here, we report that nitrogen-doped carbon nanotubes (N-CNTs) can
      be efficiently employed as a metal-free catalyst for oxidative reactions that
      allow the selective transformation of the harmful, gaseous H(2)S into solid
      sulfur. The catalyst exhibits a high stability during the test at high space
      velocity. The macroscopic shaping of the catalyst on the silicon carbide foam
      also increases its catalytic activity by improving the contact between the
      reactants and the catalyst. Such macroscopic shaping allows the avoidance of
      problems linked with transport and handling of nanoscopic materials and also
      reduces the pressure drop across the catalyst bed to a large extent.

PMID- 22134971
TI  - Intratumoral injection of taxol in vivo suppresses A549 tumor showing cytoplasmic
      vacuolization.
AB  - Based on our recent in vitro studies, this report was designed to explore the
      mechanism by which high concentration of taxol (70 uM) induced paraptosis-like
      cell death in human lung carcinoma (A549) cells, and to evaluate the therapeutic
      efficacy of taxol using A549 tumor-bearing mice in vivo. Exposure of cells to
      taxol induced time-dependent cytotoxicity and cytoplasmic vacuolization without
      the involvement of Bax, Bak, Mcl-1, Bcl-XL, and caspase-3. Although taxol
      treatment induced activating transcription factor 6 (ATF6) cleavage indicative of
      endoplasmic reticulum (ER) stress, silencing ATF6 by shATF6 did not prevent taxol
      induced both cytotoxcity and cytoplasmic vacuolization, suggesting that taxol
      induced cytoplasmic vacuolization and cell death were not due to ER stress.
      Moreover, taxol-treated cells did not show DNA fragmentation and loss of
      mitochondrial membrane potential, the typical characteristics of apoptosis. In
      addition, taxol-induced cytoplasmic vacuolization did not show the cellular
      lysis, the characteristics of oncosis, and positive of beta-galactosidase, the
      characteristic of senescence, indicating that taxol induced paraptosis-like cell
      death is neither oncosis nor senescence. Moreover, our in vivo data showed that
      intratumoral injection of taxol (50 mg/kg) in A549 tumor xenograft mice on day 1
      and day 19 potently suppressed tumor growth showing significant ER vacuolization
      without toxicity. In conclusion, high concentration of taxol exhibits a
      significant anticancer activity by inducing paraptosis-like cell death in vitro
      and in vivo, without significant toxicity, suggesting a promising therapeutic
      strategy for apoptosis-resistance cancer by inducing ER vacuolization.

PMID- 22134972
TI  - Inhibition of heat shock transcription factor binding by a linear polyamide
      binding in an unusual 1:1 mode.
AB  - Heat shock proteins (HSPs) are known to protect cells from heat, oxidative
      stress, and the cytotoxic effects of drugs, and thus can enhance cancer cell
      survival. As a result, HSPs are a newly emerging class of protein targets for
      chemotherapy. Among the various HSPs, the HSP70 family is the most highly
      conserved and prevalent. Herein we describe the development of a beta-alanine
      rich linear polyamide that binds the GGA heat shock elements (HSEs) 3 and 4 in
      the HSP70 promoter in an unusual 1:1 mode and inhibits heat shock transcription
      factor 1 (HSF1) binding in vitro.

PMID- 22134973
TI  - Aripiprazole plus divalproex for recently manic or mixed patients with bipolar I
      disorder: a 6-month, randomized, placebo-controlled, double-blind maintenance
      trial.
AB  - OBJECTIVES: The goal of this study was to investigate the safety and efficacy in
      preventing relapse of a mood episode in recently manic or mixed episode patients
      with bipolar I disorder stabilized with aripiprazole and divalproex combination.
      METHODS: This randomized, 24-week, double-blind, placebo-controlled multicenter
      study enrolled patients from 23 centers in Korea. Patients with bipolar I
      disorder who had manic or mixed episode entered a 6-week open-label stabilization
      phase. After meeting stabilization criteria, 83 patients were randomly assigned
      to placebo + divalproex or aripiprazole + divalproex treatment group for the 24
      week, double-blind maintenance phase. RESULTS: During the 6-month double-blind
      treatment, the time to relapse of any mood episode in the aripiprazole group was
      longer than the placebo group, but the difference did not reach statistical
      significance (p = 0.098). After controlling for mean divalproex level, the time
      to depressive episode relapse in the aripiprazole group was longer than those in
      the placebo group (p = 0.029). Weight gain (>= 7% increase) occurred in 22.5%
      aripiprazole group and 18.6% placebo group (p = 0.787). CONCLUSIONS: In this
      study, relapse of mood episode occurred fewer and later for aripiprazole with
      divalproex treatment than divalproex monotherapy, but the differences were not
      statistically significant.

PMID- 22134975
TI  - Micro- and nanofluidics in Asia Pacific.

PMID- 22134976
TI  - Recent advances in single-molecule detection on micro- and nano-fluidic devices.
AB  - Single-molecule detection (SMD) allows static and dynamic heterogeneities from
      seemingly equal molecules to be revealed in the studies of molecular structures
      and intra- and inter-molecular interactions. Micro- and nanometer-sized
      structures, including channels, chambers, droplets, etc., in microfluidic and
      nanofluidic devices allow diffusion-controlled reactions to be accelerated and
      provide high signal-to-noise ratio for optical signals. These two active research
      frontiers have been combined to provide unprecedented capabilities for chemical
      and biological studies. This review summarizes the advances of SMD performed on
      microfluidic and nanofluidic devices published in the past five years. The latest
      developments on optical SMD methods, microfluidic SMD platforms, and on-chip SMD
      applications are discussed herein and future development directions are also
      envisioned.

PMID- 22134977
TI  - PDMS microchip coated with polydopamine/gold nanoparticles hybrid for efficient
      electrophoresis separation of amino acids.
AB  - In this paper, a novel, simple, economical and environmentally friendly method
      based on in situ chemically induced synthesis strategy was designed and developed
      for the modification of a poly(dimethylsiloxane) (PDMS) microchip channel with
      polydopamine/gold nanoparticles (PDA/Au NPs) to create a hydrophilic and
      biofouling resistant surface. Dopamine as a reductant and a monomer, and HAuCl(4)
      as an oxidant to trigger dopamine polymerization and the source of metallic
      nanoparticles, were filled into the PDMS microchannel to yield in situ a well
      distributed and robust PDA/Au NP coating. Au NPs were highly and uniformly
      dispersed in/on the PDA matrix with a narrow size distribution, as verified by
      scanning electron microscopy and UV-vis spectra. Compared with the native PDMS
      microchannel, the modified surfaces exhibited much better wettability, high
      stability and suppressed electroosmotic mobility, and less nonspecific adsorption
      towards biomolecules. The water contact angle and EOF of PDA/Au NP-coated PDMS
      microchip were measured to be 13 degrees  and 4.17*10(-4) cm(2)/V s, compared to
      those of 111 degrees  and 5.33*10(-4) cm(2)/V s from the native one,
      respectively. Fast and efficient separations of five amino acids such as
      arginine, proline, histidine, valine and threonine suggested greatly improved
      electrophoretic performance of the PDA/Au NP-functionalized PDMS microchips. This
      one-step procedure offers an effective approach for a biomimetic surface design
      on microfluidic chips, which is promising in high-throughput and complex
      biological analysis.

PMID- 22134974
TI  - Dysregulation of glucose metabolism in HIV patients: epidemiology, mechanisms,
      and management.
AB  - HIV-infected patients on highly active antiretroviral therapy (HAART) have
      increased prevalence of a number of chronic metabolic disorders of multifactorial
      but unclear etiology. These include disorders of lipid metabolism with or without
      lipodystrophy, insulin resistance, and an increased prevalence of impaired
      glucose tolerance, diabetes mellitus, and cardiometabolic syndrome. While much
      attention has been focused on the lipid and cardiovascular disorders, few
      investigations have attempted to characterize the prevalence, incidence,
      etiology, mechanisms, and management of glycemic disorders in HIV patients. In
      this review, we have focused specifically on a comprehensive assessment of
      dysglycemia in the context of HIV infection and HAART.

PMID- 22134978
TI  - Polyelectrolytes in multivalent salt solutions.
AB  - We study conformational and electrophoretic properties of polyelectrolytes (PEs)
      in tetravalent salt solutions under the action of electric fields by means of
      molecular dynamics simulations. Chain conformations are found to have a sensitive
      dependence on the salt concentration C(s). As C(s) is increased, the chains first
      shrink to a globular structure and subsequently re-expand above a critical
      concentration C(s)*. An external electric field can further alter the chain
      conformation. If the field strength E is larger than a critical value E*, the
      chains are elongated. E* is shown to be a function of C(s) by using two
      estimators E(I)* and E(II)* through the study of the polarization energy and the
      onset point of chain unfolding, respectively. The electrophoretic mobility of the
      chains depends strongly on C(s), and the magnitude increases significantly,
      accompanying the chain unfolding, when E>E(II)*. We study the condensed ion
      distributions modified by electric fields and discuss the connection of the
      modification with the change of chain morphology and mobility. Finally, E* is
      studied by varying the chain length N. The inflection point is used as a third
      estimator E(III)*. E(III)* scales as N(-0.63(4)) and N(-0.76(2)) at C(s) =0.0 and
      C(s)*, respectively. E(II)* follows a similar scaling law to E(III)* but a
      crossover appears at C(s) =C(s)* when N is small. The E(I)* estimator fails to
      predict the critical field, which is due to oversimplifying the critical
      polarization energy to the thermal energy. Our results provide valuable
      information to understand the electrokinetics of PE solutions at the molecular
      level and could be helpful in micro/nanofluidic applications.

PMID- 22134979
TI  - 2-D t-ITP/CZE determination of clinical urinary proteins using a microfluidic
      chip capillary electrophoresis device.
AB  - To replace the time-consuming sample pretreatment procedure, a microfluidic chip
      CE device incorporating on-chip sample desalting/preconcentration with transient
      isotachophoresis (ITP)/capillary zone electrophoresis (CZE) was fabricated to
      perform sequential on-chip sample pretreatment and CE determination of four
      urinary proteins in clinical samples. On-chip sample desalting, clean-up and
      analyte preconcentration enable removing interfering sample matrix prior to
      transferring analytes to separation capillary for transient ITP/CZE
      determination. Four important urinary proteins transferrin, beta2-microglobulin,
      human serum albumin (HSA) and immunoglobulin G (IgG), investigated were shown to
      achieve quantitation limits sufficiently high to meet medical requirements,
      sensitivity enhancement up to 40-fold and detection limits down to 0.3, 0.05,
      0.6, 0.5 mg/L, respectively. Compared to the stacking effect, the use of a large
      sample size was found to be the major factor for sensitivity enhancement. The
      method reliability is established by close to 100% recoveries and statistical
      agreement of results from the method developed with currently used clinical radio
      immunoassay method for all four proteins investigated. Moreover, an assay time of
      less than 10 min is needed in the method developed as compared to 7 h for the
      radio-immunoassay method.

PMID- 22134980
TI  - Rapid detection of dysfunctional high-density lipoproteins using isoelectric
      focusing-based microfluidic device to diagnose senescence-related disease.
AB  - Recently, we reported elevated levels of advanced glycated end products (AGEs) in
      human high-density lipoproteins (HDL), with fragmentation of apoA-I in an elderly
      group, compared with a younger group. More dysfunctional HDL from human plasma
      was demonstrated in the elderly group, including reconstituted HDL containing
      glycated apoA-I (gA-I-rHDL) with elevation of AGEs. Based on SDS-PAGE analysis,
      HDL(3) from the elderly group (E-HDL(3)) exhibited increased multimerization with
      increased smear band intensity compared to HDL(3) from the younger group (Y
      HDL(3)). According to isoelectric focusing gel analysis, gA-I-rHDL and E-HDL(3)
      showed electromobility to the basic region of pH with a broader band range. In a
      microfluidic channel, E-HDL(3) had faster mobility with a broader range and a
      higher isoelectric point (pI, approximately 8.1), whereas Y-HDL(3) showed a
      narrow band range with a lower pI (approximately 6.9). In conclusion, gA-I-rHDL
      and E-HDL share several electrophoretic properties with multimerization and
      faster mobility in microfluidic channels, depending on the isoelectric point.
      These results can be applied to develop a rapid detection system for modified HDL
      to predict the extent of aging and aging-related metabolic diseases, such as
      cardiovascular disease and diabetes.

PMID- 22134981
TI  - Microfluidic chip-capillary electrophoresis with dynamic multi-segment standard
      addition for rapidly identifying nephrolithiasis markers in urine.
AB  - A microchip-CE device was fabricated for bed-side monitoring of nephrolithiasis
      biomarkers in urine by incorporating on-chip continuous passive mixing and
      standard addition to reduce sample matrix interference, increase sample
      throughput and eliminate accessories for active mixing. Under optimized
      conditions with buffer containing 20 mM borate and 0.5 mM CTAB at pH 10.3, sample
      and standards injected electrokinetically at -350 V for 10 s for online mixing in
      a Y-merging flow microchannel prior to CE separation and UV detection at 210 nm,
      both inhibitors (citrate, CA) and promoters (oxalate, OA and uric acid, UA) for
      nephrolithiasis can be separated and determined in human urine in a single run
      completed within 10 min after a simple 50-fold sample dilution and filtering.
      Satisfactory working ranges from 0.13-40, 0.25-40 and 0.025-40 mM, LOD 2.6, 6.1
      and 0.7 MUM, repeatability (%RSD, n=5) for migration time 1.40, 1.43, 0.47 and
      peak area 4.46, 6.10, 1.98, respectively, for CA, OA and UA are obtained for
      urine samples. The use of on-chip standard addition is shown to improve
      repeatability of the migration time, assist the identification of nephrolithiasis
      markers from difficult samples with noisy baseline and enlarge the working range
      for nephrolithiasis marker determination. The device developed can be used for
      both routine and emergency monitoring to deliver results on demand for bedside
      monitoring and public health protection. It provides an early detection of
      nephrolithiasis to enable timely treatments, ease anxiety of parents for neonates
      consuming suspected contaminated food, and quick results for patients in a
      critical condition.

PMID- 22134984
TI  - Three-dimensionally ordered macroporous nitroxide polymer brush electrodes
      prepared by surface-initiated atom transfer polymerization for organic radical
      batteries.
AB  - The synthesis and electrochemical performance of three-dimensionally ordered
      macroporous (3DOM) nitroxide polymer brush electrodes for organic radical
      batteries are reported. The 3DOM electrodes are synthesized via polystyrene
      colloidal crystal templating with electropolymerization of polypyrrole,
      modification of surface initiator, and surface-initiated atom transfer radical
      polymerization. The discharge capacity of the 3DOM electrodes is proportional to
      the thickness of the inverse opal. The discharge capacity of the 3DOM electrode
      at a discharge rate of 5 C is 40 times higher than that of the planar electrode;
      its cycle-life performance exhibits 96.1% retention after 250 cycles. 

PMID- 22134985
TI  - Catalysis based on nanocrystals with well-defined facets.
AB  - Using bottom-up chemistry techniques, the composition, size, and shape in
      particular can now be controlled uniformly for each and every nanocrystal (NC).
      Research into shape-controlled NCs have shown that the catalytic properties of a
      material are sensitive not only to the size but also to the shape of the NCs as a
      consequence of well-defined facets. These findings are of great importance for
      modern heterogeneous catalysis research. First, a rational synthesis of catalysts
      might be achieved, since desired activity and selectivity would be acquired by
      simply tuning the shape, that is, the exposed crystal facets, of a NC catalyst.
      Second, shape-controlled NCs are relatively simple systems, in contrast to
      traditional complex solids, suggesting that they may serve as novel model
      catalysts to bridge the gap between model surfaces and real catalysts.

PMID- 22134986
TI  - SMILE silencing and PMA activation gene networks in HeLa cells: comparison with
      kidney transplantation gene networks.
AB  - Recent findings indicated that the SMILE gene may be involved in kidney graft
      operational tolerance in human. This gene was found to be up-regulated in blood
      from patients with a well functioning kidney transplant in the absence of
      immunosuppression compared to other transplanted recipients with clinically
      different status. A microarray study of SMILE knock-down and phorbol 12-myristate
      13-acetate (PMA) activation in HeLa cells was herein compared to our earlier
      analysis based on microarray data of kidney allograft tolerance and rejection in
      humans and in a rat model of allograft transplantation to determine possible new
      genes and gene networks involved in kidney transplantation. The nearest neighbors
      at the intersection of the SMILE knock-down network with the human
      tolerance/rejection networks are shown to be NPHS1 and ARRB2, the former
      (Nephrin) being involved in kidney podocyte function, and the decrease of the
      latter (Arrestin beta2) being recently shown to be involved in monocyte
      activation during acute kidney allograft rejection in rat. Moreover, another one
      of the neighbors at the intersection of SMILE network and tolerance/rejection
      networks is XBP-1, that we report previously to be increased, at a transcript
      level, after ER stress in SMILE silenced cells. Finally, in this study, we also
      show that topological properties (both local and global) of joint SMILE knock
      down network-tolerance/rejection networks and joint PMA activation network
      tolerance/rejection networks in rat and human are essentially different, likely
      due to the inherent nature of the gene SMILE and the mitogen PMA, that do not act
      the same way on genes and do not interfere the same way on networks. We also show
      that interestingly SMILE networks contain more feed-forward loop (FFL) motifs and
      thus SMILE calls for a more fine-tuned genetic regulation.

PMID- 22134987
TI  - Prilezhaev dihydroxylation of olefins in a continuous flow process.
AB  - Epoxidation of both terminal and non-terminal olefins with peroxy acids is a well
      established and powerful tool in a wide variety of chemical processes. In an
      additional step, the epoxide can be readily converted into the corresponding
      trans-diol. Batch-wise scale-up, however, is often troublesome because of the
      thermal instability and explosive character of the peroxy acids involved. This
      article describes the design and semi-automated optimization of a continuous flow
      process and subsequent scale-up to preparative production volumes in an
      intrinsically safe manner.

PMID- 22134988
TI  - Glycine fluoromethylketones as SENP-specific activity based probes.
AB  - We report here the synthesis and biochemical properties of a new peptidyl
      activity-based probe 1 for SUMO proteases, SENPs. The activity-based probe has at
      its C terminus a glycine-derived fluoromethylketone moiety as a reactive group
      designed to target the active-site cysteine of SENPs. Based on a study of the
      interactions between SENPs and SUMOs, we introduced further design elements that
      allow the activity-based probe to selectively target SENPs at low micromolar to
      high nanomolar concentrations. Moreover, 1 out-competes SUMO1 from the reversible
      SUMO1-SENP1 complex, thus suggesting that 1 and SUMO1 share a common binding site
      on SENP1.

PMID- 22134989
TI  - Nijmegen observer-rated depression scale for detection of depression in nursing
      home residents.
AB  - OBJECTIVE: This study aims to test the accuracy of the Nijmegen observer-rated
      depression (NORD) scale, a new short scale for screening of depression in nursing
      home (NH) residents with and without dementia. METHODS: This cross-sectional
      study with 103 residents with dementia (N = 19 depressed) and 72 residents
      without dementia (N = 10 depressed) was undertaken in 13 Dutch NH units. An
      elderly care physician and a psychologist of each unit assessed residents for the
      presence of clinical depression. Primary professional caregivers administered the
      NORD scale. RESULTS: Five of the six proposed items showed acceptable performance
      in screening for depression. Receiver operating characteristic analyses revealed
      significant areas under the empirical curve (AUC) for the 5-item NORD scale in
      the total sample (AUC = 0.83, p < 0.001), as well as in residents with dementia
      (AUC = 0.84, p < 0.001) and without dementia (AUC = 0.84, p < 0.001). The cutoff
      score of >1 showed the highest sum of sensitivity (100) and specificity (69) in
      non-dementia and >2 the highest sum of sensitivity (79) and specificity (77) in
      dementia. The cutoff score of >1 showed the lowest negative likelihood ratio of
      0.0 in non-dementia and of 0.2 in dementia. The highest positive likelihood
      ratios were found for the cutoff of >2 in non-dementia (3.4) and for >4 in
      dementia (26.5). CONCLUSION: The 5-item NORD scale showed acceptable accuracy
      comparable with those of more extensive scales in other studies. It is easy and
      quick to administer and can be used for screening of depression in NH residents
      with or without dementia.

PMID- 22134990
TI  - Removal of cadmium by combining deferasirox and desferrioxamine chelators in
      rats.
AB  - An investigation was conducted to evaluate the ability of two chelators,
      deferasirox and desferrioxamine (DFO), in removing cadmium from biological
      system. The potential efficiency of those chelators were investigated after
      cadmium administration for 60 days following two dose levels of 20 and 40 mg/kg
      body weight daily to male rats. However, abnormalities were observed in clinical
      signs after cadmium administration, such as yellowish discoloration of hair,
      flaccid and hypotonic muscles, irritability, weakness and loss of weight. The
      hypothesis that the two chelators might be more efficient as combined therapy
      than single therapy in removing metal ions from the body was considered. In this
      way, two known chelators, deferasirox and DFO were chosen and tested in the acute
      rat model. The chelation therapy results show that deferasirox and DFO are able
      (?)to remove cadmium ions from the body, while iron concentration returned to the
      normal level and symptoms are decreased.

PMID- 22134991
TI  - Out of hours GPs' "culture of avoiding blame" is putting patients at risk.

PMID- 22134992
TI  - [Oscillations in the cardiovascular system--physical models for the
      interpretation of physiological phenomena].
AB  - We discuss the foundations of the theory of homeostasis within the framework of
      modern physics. We analyse the paradigm of homeostasis, which is based on the
      physical assumption that the internal environment undergoes random fluctuations
      around a steady state equilibrium. We show how the notion of homeodynamics
      extends the concept of homeostasis. We introduce the paradigm of the phase
      sensitivity of regulatory activity which supplements the classical paradigm of
      the tonic character of such activity.

PMID- 22134993
TI  - [Overview on omega-3 polyunsaturated fatty acids and heart failure].
AB  - Despite aggressive pharmacotherapy, heart failure is still clinical problem.
      Current therapies improve clinical symptoms and slow progression to heart
      failure, but overall the prognosis remains poor. Evidence from epidemiological,
      clinical and experimental studies indicates a beneficial role of the omega-3
      polyunsaturated fatty acids (omega-3 PUFA) found in fish oils in the prevention
      and management of heart failure. Although the mechanisms is still unclear,
      clinical and animals studies indicate that the benefits of omega-3 PUFA may be
      attributed to a number of distinct biological effects on lipoprotein metabolism,
      inflammation response and mitochondrial function. This review summarise the data
      related to use of omega-3 PUFA supplementation as a potential treatment for heart
      failure and discussed possible mechanism of action.

PMID- 22134994
TI  - [The influence of the biological age on function of endothelial progenitor
      cells].
AB  - Aging in relation to organism biology is a gradual loss of restoration potential.
      Biological age is a subject of interest in many fields as genetics, nephrology
      and oncology. Endothelial progenitor cells (EPCs) are responsible for
      regeneration of endothelium. The dysfunction of EPCs, which seems to be the
      consequence of the aging process, may lead to the development of cardiovascular
      disorders. EPCs disturbances may reduce EPCs number, impair the migration ability
      and clonogenic potential of EPCs. This paper presents some aspects of aging
      process of EPCs according to the latest reports concerning the biological age. It
      contains the description of biological age conception. Moreover it shows the
      chosen markers of biological age (telomeres, proteins regulating cell cycle,
      proteases) and modulating factors like administered medications and ingested
      chemical compounds. Some therapeutic actions which may interfere in biological
      age are also presented.

PMID- 22134995
TI  - [Induced pluripotential stem cells--perspectives of clinical application in
      cardiovascular diseases].
AB  - In 2006 were reported first results on induction of pluripotential stem cells
      from adult somatic cells. It was successfully performed transfection by using
      genetic engineering and the effective overexpression of four transcription
      factors, OCT4, SOX2, c-MYC, KLF4 has been obtained. Thus pluripotency was induced
      in finally differentiated mammalian somatic cells with comparable to embryonic
      stem cells morphological and transcriptomic profiles. Before, it was only
      possible by using cloning procedure with diploid nucleus transfer to enucleated
      oocyte. Soon after range of reports appeared describing genetic modifications of
      variety human somatic cells enabling them pluripotency. The aim of this article
      was to summarise a present knowledge with several listed goals to be achieved
      before the first clinical trials with induced pluripotent stem cells can be
      feasible. Aspects of cardiovascular diseases treatment have been outlined.

PMID- 22134996
TI  - [Relationship between heart development and pathogenesis of congenital heart
      defects in current literature].
AB  - This work presents current ideas on embryonic heart development and is an attempt
      to elucidate pathogenesis of congenital heart defects. The heart develops from 2
      areas, the so-called "heart fields", which differ in the expression of various
      genes and in sensitivity to certain substances (for example retinoid acid). Heart
      fields are the source of cardiomyocytes and endocardial endothelial cells for the
      developing heart tube. Neural crest cells attaining the heart take part in the
      formation of tunica media of great vessels and the aorto-pulmonary septum. An
      interaction between the cells of the secondary heart field and neural crest cells
      migrating to the heart plays a significant role in heart development. This
      interaction is accomplished by various mediators released into the cell
      environment (e.g. activation of Notch, which induces secretion of growth factors
      such as Fgf8). Disturbances in signaling between these cellular populations lead
      to malformations of the cardiac outflow tract. The sinus venosus is the source of
      endothelial cells of the coronary vasculature, whereas the proepicardium provides
      cells for the epicardium, smooth muscle cells and fibroblasts.

PMID- 22134997
TI  - [Optimalisation of treatment with vitamin K antagonists--the role of gene
      polymorphisms].
AB  - The magnitude of a maintenance vitamin K antagonist (VKA) dose during
      anticoagulant therapy depends not only on clinical, environmental, and
      demographic factors, but also on genetic factors. Known genetic polymorphisms
      explain 40-50% of the variance in VKA dosing. Polymorphisms of two genes encoding
      enzymes involved in vitamin K and/or VKA metabolism such as vitamin K epoxide
      reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 isoform (CYP2C9)
      play a key role in this variance. Polymorphisms of cytochrome P450 4F2 isoform
      (CYP4F2), apolipoprotein E (APOE) and gamma-glutamyl carboxylase (GGCX) are of
      minor or negligible importance. In European populations, 3 haplotypes of VKORC1,
      VKORC1*2, VKORC1*3 and VKORC1*4--have been identified and they determined 99% of
      genetic variability of this enzyme. The presence of -1639G > A VKORC1
      polymorphism is associated with increased VKA dose requirements. Allelic variants
      of CYP2C9*2 and CYP2C9*3 (found in 8-12% and 3-8% of individuals, respectively)
      increase the risk of haemorrhage due to slow VKA metabolism, especially at the
      therapy initiation. Pharmacogenetic algorithms incorporating VKORC1 and CYP2C9
      genotypes help to predict the VKA dosage, particularly if the dose requirements
      are low or moderate. However, there is no compelling evidence showing reduced
      risk for clinical adverse events during VKA therapy following the identification
      of the patient's genetic profile.

PMID- 22134998
TI  - [The role of nitric oxide, hydrogen sulfide and carbon monoxide in the regulation
      of the circulatory system and their pharmacotherapeutic potential].
AB  - In the eighties of the twentieth century nitric oxide (NO) was identified as the
      endothelium-derived relaxing factor. This discovery has triggered an interest in
      gaseous transmitters and their role in the regulation of the circulatory system.
      Recently, it has become evident that hydrogen sulfide (H2S) and carbon monoxide
      are also involved in physiological and pathological processes in the
      cardiovascular system. Nitrates that have been used for over a century and
      nebivolol, a third-generation b-blocker with vasodilating properties by
      increasing bioavailability of NO, provide convincing arguments that the compounds
      acting via NO pathway will remain an important class of cardiovascular drugs. A
      rapidly growing number of publications on functions of H2S in the circulatory
      system suggests that the gaseous transmitter may become a promising target for
      new treatment strategies in cardiovascular diseases. This review is focused on
      the role of gaseous transmitters in the regulation of the cardiovascular system
      and their pharmacotherapeutic potential.

PMID- 22134999
TI  - [Cardiac magnetic resonance imaging of acute myocardial infarction].
AB  - Area at risk, infarct area, the size of no-reflow phenomenon and finally left
      ventricular function determine immediate and long-term outcome in patients with
      acute myocardial infarction (AMI). Cardiac magnetic resonance imaging is a gold
      standard technique for evaluation of left ventricular volumes and function and
      therefore has evolved into an important diagnostic tool in the assessment of
      patients with AMI. Increased free water content in the infracted myocardium
      prolongs the T2-relaxation time. Differences in T2-relaxation time are clinically
      useful for detection of area of risk whereas first-pass technique is useful for
      the assessment of areas with perfusion deficit at rest. Myocardial necrosis
      appears hyper-enhanced in comparison to the normal myocardium after contrast
      injection with delayed enhancement (DE) technique. Experimental and clinical
      studies indicate that extent of DE closely correlates with infarct size and
      predicts functional recovery of postinfarcted myocardium. The hypo-enhanced zone
      usually located in the core of hyper-enhanced region indicates microvascular
      obstruction (MVO) and corresponds with the area of no-reflow as defined by
      histopathology. The presence of MVO is associated with impaired functional
      recovery after AMI.

PMID- 22135002
TI  - NDRG2 down-regulation and CD24 up-regulation promote tumor aggravation and poor
      survival in patients with gallbladder carcinoma.
AB  - Recent studies have demonstrated that N-Myc downstream-regulated gene 2 (NDRG2)
      may reduce the metastatic potential of breast cancer and hepatocellular carcinoma
      cells by regulating the expression of CD24, which is expressed in a large variety
      of solid tumors. The aim of this study was to clarify the clinical value of NDRG2
      and CD24 expression in primary gallbladder carcinoma (GBC). One hundred and
      thirty GBC tissues were evaluated by immunohistochemistry for NDRG2 and CD24
      expression. The associations of NDRG2 and CD24 expression with the
      clinicopathological characteristics and the overall survival of patients with GBC
      were analyzed. NDRG2 and CD24 were positively expressed in 49/130 (37.69%) and
      107/130 (82.31%) of GBC tissues, respectively. In addition, the tumors with the
      down-regulation of NDRG2 and the up-regulation of CD24 more frequently had lymph
      node metastasis and lymphovascular invasion. Moreover, the tumors with the down
      regulation of NDRG2 and the up-regulation of CD24 tended to show deeper invasion
      depth and higher TNM stage. There was a negative correlation between NDRG2
      expression and CD24 expression in GBC tissues (r = -0.86, P < 0.001). The
      patients with NDRG2 negative expression correlated with poor prognosis of GBC (P
      = 0.01), as opposed to CD24 (P = 0.01). The survival rate of the patients with
      NDRG2-/CD24+ expression was the lowest (P < 0.001), and conjoined expression of
      NDRG2-/CD24+ was an independent prognostic indicator of GBC (P = 0.003). Our data
      suggest that NDRG2 down-regulation or CD24 up-regulation is an important feature
      of GBC. A combined detection of NDRG2/CD24 co-expression may benefit us in
      prediction of the prognosis in GBC.

PMID- 22135003
TI  - Therapeutic use of creatine in brain or heart ischemia: available data and future
      perspectives.
AB  - Creatine (Cr) is essential in safeguarding ATP levels and in moving ATP from its
      production site (mitochondria) to the cytoplasmic regions where it is used.
      Moreover, it has effects unrelated to energy metabolism, such as free radical
      scavenging, antiapoptotic action, and protection against excitotoxicity. Recent
      research has studied Cr-derived compounds (Cr benzyl ester and phos-pho-Cr
      magnesium complex) that reproduce the neuroprotective effects of Cr while better
      crossing the neuronal plasma membrane and, hopefully, the blood-brain barrier
      (BBB). Intracellular levels of Cr can be increased by incubation with Cr or some
      of its derivatives, and this increase is protective against anoxic or ischemic
      damage. A large amount of experimental evidence shows that pretreatment with Cr
      is capable of reducing the damage induced by ischemia or anoxia in both heart and
      brain, and that such treatment may also be useful even after stroke or myocardial
      infarction (MI) has already occurred. Cr has been safely administered to patients
      affected by several neurological diseases, yet it has never been tested in human
      brain ischemia, the condition where its rationale is strongest. Phosphocreatine
      (PCr) has been administered after human MI, where it proved to be safe and
      probably helpful. Cr should be tested in the prophylactic protection against
      human brain ischemia and either Cr or PCr should be further tested in MI.
      Moreover, Cr- or PCr-derived drugs should be developed in order to overcome these
      molecules' limitations in crossing the BBB and the cell plasma membrane.

PMID- 22135004
TI  - Hypoxia inhibits the spontaneous calcification of bone marrow-derived mesenchymal
      stem cells.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the popular seed cells
      for regenerative medicine, and there has been a rapid increase in the number of
      BM-MSC-based clinical trials. However, the safety of these cells should also be
      closely studied. In this study, spontaneous calcification of BM-MSCs from rats
      was evaluated in normoxia (20% O(2)) without osteogenic medium after continuous
      culture for 21 days; obvious mineralized nodules were observed, which were
      positive for Alizarin Red, collagen-I (Col-I), osteocalcin (OC) and alkaline
      phosphatase (ALP), and mainly consisted of C, O and Ca elements. Interestingly,
      hypoxia (2% O(2)) significantly inhibited this spontaneous calcification. In
      addition, the ALP and calcium content of rBM-MSCs were sharply reduced. Based on
      RT-PCR results, the expression of osteogenic genes (Cbfa1/Runx2, Col-I, ALP, and
      OC) was reduced compared to that in normoxia. These results demonstrate a natural
      and unique characterization of rat BM-MSCs in normoxia after continuous culture
      and highlight the inhibiting effects of hypoxia. Finally, this study contributes
      to the information regarding the application of BM-MSCs in the regeneration of
      various tissues.

PMID- 22135005
TI  - Conformational selection versus induced fit in kinases: the case of PI3K-gamma.

PMID- 22135006
TI  - Triblock copolymer based on poly(propylene oxide) and poly(1-[11-acryloylundecyl]
      3-methyl-imidazolium bromide).
AB  - The controlled atom transfer radical polymerization of an ionic liquid, 1-(11
      acryloylundecyl)-3-methyl imidazolium bromide (ILBr), from both ends of a
      telechelic poly(propylene oxide) (PPO) macroinitiator, end-functionalized with
      bromoisobutyryloyl is reported. The resulting highly water-soluble triblock,
      poly(ILBr-b-PO-b-ILBr) is multistimuli responsive. This new class of triblocks
      exhibits classical surface activity in lowering surface tension at the air-water
      interface and in modifying wetting in waterborne coatings. It also immunizes
      model colloids against coagulation induced by Debye-Huckel (indifferent
      electrolyte) electrostatic screening. Further, sol-gel thermoreversibility is
      unexpectedly found as an additional form of stimuli responsiveness.

PMID- 22135007
TI  - Ritter reactions in flow.

PMID- 22135008
TI  - Latent class-derived subgroups of depressive symptoms in a community sample of
      older adults: the Cache County Study.
AB  - OBJECTIVE: We sought to identify possible subgroups of elders that varied in
      depressive symptomatology and to examine symptom patterns and health status
      differences between subgroups. METHODS: The Cache County memory study is a
      population-based epidemiological study of dementia with 5092 participants.
      Depressive symptoms were measured with a modified version of the diagnostic
      interview schedule-depression. There were 400 nondemented participants who
      endorsed currently (i.e., in the past 2 weeks) experiencing at least one of the
      three "gateway" depressive symptoms and then completed a full depression
      interview. Responses to all nine current depressive symptoms were modeled using
      the latent class analysis. RESULTS: Three depression subgroups were identified: a
      significantly depressed subgroup (62%), with the remainder split evenly between a
      subgroup with low probability of all symptoms (21%), and a subgroup with
      primarily psychomotor changes, sleep symptoms, and fatigue (17%). Latent class
      analysis derived subgroups of depressive symptoms and Diagnostic and statistical
      manual of mental disorders, fourth edition depression diagnostic group were
      nonredundant. Age, gender, education, marital status, early or late onset, number
      of episodes, current episode duration, and functional status were not significant
      predictors of depression subgroup. The first subgroup was more likely to be
      recently bereaved and had less physical health problems, whereas the third
      subgroup were less likely to be using antidepressants compared with the second
      subgroup. CONCLUSIONS: There are distinct subgroups of depressed elders, which
      are not redundant with the Diagnostic and statistical manual of mental disorders,
      fourth edition classification scheme, offering an alternative diagnostic approach
      to clinicians and researchers. Future work will examine whether these depressive
      symptom profiles are predictive of incident dementia and earlier mortality.

PMID- 22135009
TI  - Combinatorial roles of extrinsic and intrinsic muscles in extension strength of
      the distal interphalangeal joint.
AB  - In this study, we observed a combinatorial relationship between intrinsic and
      extrinsic muscles to extend the distal phalanx via the terminal tendon of the
      finger extensor. Eleven fresh-frozen human cadaver digit rays were used in these
      experiments (four index, four middle, three ring digits). All fingers had full
      joint motion without degenerative diseases. Fingers were individually mounted in
      a custom built jig fixed by a 1-mm Kirschner wire that was driven into the
      rotational center of the distal interphalangeal (DIP) and proximal
      interphalangeal joints. Loads were applied to the extensor digit and dorsal
      interosseous tendons without flexor tendons, via sutures attached over low
      friction pulleys. Extension forces that crossed the DIP joint were measured by a
      force transducer coupled with a materials-testing machine. We observed a steep
      inclination of the extensor forces produced by the intrinsic muscles, and there
      were no significant differences in comparisons among loads (200, 400, 600, and
      800 g). The inclination slope increased with an increase of load (p < 0.001).
      Additionally, the inclinations of the non-linear phases among all finger types
      were not statistically different. Thus, the contribution between the extrinsic
      and intrinsic muscles in providing extensor forces to the distal phalanx was
      similar.

PMID- 22135011
TI  - Retraction. I148M PNPLA3 variant and progressive liver disease: A new paradigm in
      hepatology.
AB  - Retraction: The following editorial from HEPATOLOGY, "I148M PNPLA3 variant and
      progressive liver disease: A new paradigm in hepatology", by Luca Valenti, Anna
      Alisi and Valerio Nobili, posted online on 2 December 2011 as an Accepted Article
      in Wiley Online Library (www.wileyonlinelibrary.com), has been retracted by
      agreement between the authors, the AASLD, the journal Editor in Chief, Michael H.
      Nathanson, and Wiley Periodicals, Inc. The retraction has been agreed due to the
      fact that an incorrect version was posted online. The correct version of the
      Editorial has been issued under a separate DOI, 10.1002/hep.25617.

PMID- 22135010
TI  - Antioxidant strategies in neurocritical care.
AB  - An increase in oxidative stress and overproduction of oxidizing reactive species
      plays an important role in the pathophysiology of several conditions encountered
      in the neurocritical care setting including: ischemic and hemorrhagic strokes,
      traumatic brain injury, acute respiratory distress syndrome, sepsis, and organ
      failure. The presence of oxidative stress in these conditions is supported by a
      large body of pre-clinical and clinical studies, and provides a rationale to
      support a potential therapeutic role for antioxidants. The purpose of this
      article is to briefly review the basic mechanisms and molecular biology of
      oxidative stress, summarize its role in critically ill neurological patients, and
      review available data regarding the potential role of antioxidant strategies in
      neurocritical care and future directions.

PMID- 22135012
TI  - Sequence-unrestricted, Watson-Crick recognition of double helical B-DNA by (R)
      miniPEG-gammaPNAs.

PMID- 22135014
TI  - Measurement of pulsatile motion with millisecond resolution by MRI.
AB  - We investigated a technique based on phase-contrast cine MRI combined with
      deconvolution of the phase shift waveforms to measure rapidly varying pulsatile
      motion waveforms. The technique does not require steady-state displacement during
      motion encoding. Simulations and experiments were performed in porcine liver
      samples in view of a specific application, namely the observation of transient
      displacements induced by acoustic radiation force. Simulations illustrate the
      advantages and shortcomings of the methods. For experimental validation, the
      waveforms were acquired with an ultrafast ultrasound scanner (Supersonic Imagine
      Aixplorer), and the rates of decay of the waveforms (relaxation time) were
      compared. With bipolar motion-encoding gradient of 8.4 ms, the method was able to
      measure displacement waveforms with a temporal resolution of 1 ms over a time
      course of 40 ms. Reasonable agreement was found between the rate of decay of the
      waveforms measured in ultrasound (2.8 ms) and in MRI (2.7-3.3 ms).

PMID- 22135015
TI  - Conversion of a long distally fixed uncemented revision femoral stem to a
      proximally fixed implant following fatigue fracture.
AB  - There has been increasing focus on bone conservation through proximal fixation in
      primary hip arthroplasty. However, the debate regarding fixation in revision
      arthroplasty and which factors influence implant choice remains less clear-cut.
      We report a case involving fatigue fracture of a long, distally well-fixed,
      uncemented revision stem. This was revised to a proximally fixed implant. This
      case highlights a number of issues when considering the choice of implant in hip
      revision surgery and raises the issue of bone conservation in revision surgery.
      We would suggest that in both primary and revision hip arthroplasty meticulous
      pre-operative consideration of the choice of implant should be undertaken,
      especially in the younger patient with higher expectations and functional
      demands.

PMID- 22135016
TI  - Understanding acetabular cup orientation: the importance of convention and
      defining the safe zone.
AB  - Understanding acetabular cup orientation is important in all aspects of total hip
      arthroplasty including preoperative planning, intraoperative positioning, and
      postoperative analysis. New concepts in ideal cup orientation such as 'combined
      anteversion' have emerged. Using computer navigation and three-dimensional
      imaging, the potential for accuracy and precision of implantation have improved.
      Nevertheless, the varying manner in which the terms "anteversion" and "abduction"
      are often used in the literature is indicative of a nebulous understanding of the
      complex spatial anatomy of acetabular cup orientation.

PMID- 22135017
TI  - Reliability of cup position in navigated THA in the lateral decubitus position
      using the 'flip technique'.
AB  - Malpositioning of the acetabular component in total hip arthroplasty (THA)
      increases the risk of dislocation, reduces the range of motion and may contribute
      to bearing surface wear. During computer assisted navigation, the anterior pelvic
      plane is registered intraoperatively by percutaneous palpation, but this may be
      unreliable. The aim of our study was to evaluate the reliability of imageless
      navigation in acetabular positioning employing data acquisition in the supine
      position and surgery in the lateral position ('flip technique'). We report 24
      patients affected by primary osteoarthritis undergoing THA in which implants were
      placed with a conventional free-hand technique using the acetabular transverse
      ligament for cup orientation. For imageless navigation we used Orthopilot
      Aesculap software. All patients had a postoperative computed tomography (CT) scan
      at three months, using previously validated dedicated software for cup
      orientation. Data collected using navigation software were compared with CT
      measurements. The mean acetabular inclination and anteversion recorded intra
      operatively using navigation software were respectively 41 degrees 5' (SD: 9.61)
      and 9 degrees 5' (SD: 4.01) respectively. The mean inclination and anteversion
      calculated post-operatively by the CT based image software were 44 degrees 2' (SD
      5.83) and 14 degrees 4' (SD 6.42) respectively. There was a statistically
      significant difference between the anteversion values (p=0.04). Therefore, the
      acquisition of parameters in the supine position with surgery performed in the
      lateral decubitus position creates unreliable data concerning cup anteversion
      using an imageless navigation system, and therefore the 'flip technique' cannot
      be recommended.

PMID- 22135018
TI  - BMI and gender do not influence surgical accuracy during minimally invasive total
      hip arthroplasty.
AB  - We investigated the accuracy of implant positioning during total hip arthroplasty
      (THA) through a minimally invasive approach in relation to body mass index (BMI)
      and gender by assessing 48 patients. Functional and radiological parameters were
      evaluated. BMI positively correlated with operation time (p=0.04), but BMI and
      gender had no influence on implant positioning. The Harris hip score (HHS)
      increased significantly (46.5 +/- 11.8 preoperatively, 92.1 +/- 9.7
      postoperatively, p<0.0001). The surgical approach described resulted in
      reproducibility of implant positioning independent of influence by BMI or gender.

PMID- 22135013
TI  - Molecular mechanism of active zone organization at vertebrate neuromuscular
      junctions.
AB  - Organization of presynaptic active zones is essential for development,
      plasticity, and pathology of the nervous system. Recent studies indicate a trans
      synaptic molecular mechanism that organizes the active zones by connecting the
      pre- and the postsynaptic specialization. The presynaptic component of this trans
      synaptic mechanism is comprised of cytosolic active zone proteins bound to the
      cytosolic domains of voltage-dependent calcium channels (P/Q-, N-, and L-type) on
      the presynaptic membrane. The postsynaptic component of this mechanism is the
      synapse organizer (laminin beta2) that is expressed by the postsynaptic cell and
      accumulates specifically on top of the postsynaptic specialization. The pre- and
      the postsynaptic components interact directly between the extracellular domains
      of calcium channels and laminin beta2 to anchor the presynaptic protein complex
      in front of the postsynaptic specialization. Hence, the presynaptic calcium
      channel functions as a scaffolding protein for active zone organization and as an
      ion-conducting channel for synaptic transmission. In contrast to the requirement
      of calcium influx for synaptic transmission, the formation of the active zone
      does not require the calcium influx through the calcium channels. Importantly,
      the active zones of adult synapses are not stable structures and require
      maintenance for their integrity. Furthermore, aging or diseases of the central
      and peripheral nervous system impair the active zones. This review will focus on
      the molecular mechanisms that organize the presynaptic active zones and summarize
      recent findings at the neuromuscular junctions and other synapses.

PMID- 22135019
TI  - Immunological variation between inbred laboratory mouse strains: points to
      consider in phenotyping genetically immunomodified mice.
AB  - Inbred laboratory mouse strains are highly divergent in their immune response
      patterns as a result of genetic mutations and polymorphisms. The generation of
      genetically engineered mice (GEM) has, in the past, used embryonic stem (ES)
      cells for gene targeting from various 129 substrains followed by backcrossing
      into more fecund mouse strains. Although common inbred mice are considered
      "immune competent," many have variations in their immune system-some of which
      have been described-that may affect the phenotype. Recognition of these immune
      variations among commonly used inbred mouse strains is essential for the accurate
      interpretation of expected phenotypes or those that may arise unexpectedly. In
      GEM developed to study specific components of the immune system, accurate
      evaluation of immune responses must take into consideration not only the gene of
      interest but also how the background strain and microbial milieu contribute to
      the manifestation of findings in these mice. This article discusses points to
      consider regarding immunological differences between the common inbred laboratory
      mouse strains, particularly in their use as background strains in GEM.

PMID- 22135020
TI  - Development, structure, and keratin expression in C57BL/6J mouse eccrine glands.
AB  - Eccrine sweat glands in the mouse are found only on the footpads and, when
      mature, resemble human eccrine glands. Eccrine gland anlagen were first apparent
      at 16.5 days postconception (DPC) in mouse embryos as small accumulations of
      cells in the mesenchymal tissue beneath the developing epidermis resembling hair
      follicle placodes. These cells extended into the dermis where significant cell
      organization, duct development, and evidence of the acrosyringium were observed
      in 6- to 7-postpartum day (PPD) mice. Mouse-specific keratin 1 (K1) and 10 (K10)
      expression was confined to the strata spinosum and granulosum. In 16.5 and 18.5
      DPC embryos, K14 and K17 were both expressed in the stratum basale and diffusely
      in the gland anlagen. K5 expression closely mimicked K17 throughout gland
      development. K6 expression was not observed in the developing glands of the
      embryo but was apparent in the luminal cell layer of the duct by 6 to 7 PPD. By
      21 PPD, the gland apertures appeared as depressions in the surface surrounded by
      cornified squames, and the footpad surface lacked the organized ridge and crease
      system seen in human fingers. These data serve as a valuable reference for
      investigators who use genetically engineered mice for skin research.

PMID- 22135021
TI  - Molecular epidemiology of a household outbreak of Shiga-toxin-producing
      Escherichia coli in Poland due to secondary transmission of STEC O104:H4 from
      Germany.
AB  - We characterized two STEC O104 : H4 clinical isolates collected in Poland from a
      7-year-old boy with haemolytic uraemic syndrome (HUS) and his nanny. This
      household outbreak began on 29 May 2011. Because of its time-frame, the outbreak
      was assumed to be part of the international STEC O104 : H4 outbreak that arose in
      Germany in May 2011. The two Polish isolates were Shiga-toxin-producing
      Escherichia coli (stx2 lpf) with enteroaggregative E. coli pathotype (aggR aap
      aggA), thereby sharing the unique virulence properties of the epidemic STEC O104
      : H4 strain from the international outbreak. The Polish isolates were multi-drug
      resistant and carried bla(TEM), strA, strB, tetA, sul1 and sul2 markers together
      with the bla(CTX-M-15) gene for CTX-M-15 extended-spectrum beta-lactamase. PFGE
      patterns and plasmid profiles of the Polish isolates and the epidemic STEC O104 :
      H4 strain corresponded closely. This finding suggested an epidemiological link
      between the Polish STEC O104 : H4 isolates and the international outbreak.
      Retrospective serological investigations proved person-to-person transmission of
      the epidemic STEC O104 : H4 strain from a father who had visited Dortmund,
      Germany, to his 7-year-old son in Gizycko, Poland. To the best of our knowledge,
      this is the first report of household transmission of Shiga-toxin-producing E.
      coli in Poland.

PMID- 22135022
TI  - Accuracy of using the lytA gene to distinguish Streptococcus pneumoniae from
      related species.
AB  - The need for a microbial identification of Streptococcus pneumoniae independent
      of culture methods has resulted in the introduction of other laboratory
      principles. The verification of a proper and exclusive gene for the detection of
      the pneumococcus by nucleic acid-based tests is, however, still unresolved. A
      previously published lytA-gene-specific real-time PCR method was applied to a
      panel of bacterial strains to clarify the analytical sensitivity and specificity
      of a PCR assay targeting this gene. Furthermore, a phylogenetic analysis of
      published lytA gene sequences was performed to look at gene sequence differences
      and the theoretical match with the primers and probes. The lytA-gene-specific PCR
      detected 46/46 S. pneumoniae isolates. All 49 of the non-pneumococcal isolates
      tested negative, including 22 isolates from the mitis group streptococci.
      Phylogenetic analysis of 94 sequences of the lytA gene from different strains of
      S. pneumoniae, Streptococcus mitis and Streptococcus pseudopneumoniae showed that
      70/87 S. pneumoniae sequences constituted one cluster and a further six sequences
      were outside but adjacent to this cluster, all with a complete match with primers
      and probes. The remaining 11 S. pneumoniae strains could be placed in a different
      cluster, which also contained the five S. mitis and two S. pseudopneumoniae
      strains. All strains had no match with primers and probes. The S. pneumoniae
      strains in the second cluster were all characterized by being bile-insoluble, an
      infrequent pneumococcal phenotype. Routine laboratories can utilize the
      additional observation that pneumococci that were negative by the specific PCR
      also carried the phenotype of bile insolubility, thereby observing the incidence
      of false-negative results produced by the PCR assay. The real-time PCR targeting
      the lytA gene thus constitutes a sensitive and specific assay that distinguishes
      S. pneumoniae from its close relatives in the mitis group.

PMID- 22135023
TI  - A comprehensive microbiological evaluation of fifty-four patients undergoing
      revision surgery due to prosthetic joint loosening.
AB  - The diagnosis of a chronic prosthetic joint infection (PJI) is challenging, and
      no consensus exists regarding how best to define the criteria required for
      microbiological identification. A general view is that culture of periprosthetic
      biopsies suffers from inadequate sensitivity. Recently, molecular analyses have
      been employed in some studies but the specificity of molecular analyses has been
      questioned, mainly due to contamination issues. In a prospective study of 54
      patients undergoing revision surgery due to prosthetic joint loosening, we
      focused on two aspects of microbiological diagnosis of chronic PJI. First, by
      collecting diagnostic specimens in a highly standardized manner, we aimed at
      investigating the adequacy of various specimens by performing quantitative
      bacteriological culture. Second, we designed and performed real-time 16S rRNA
      gene PCR analysis with particular emphasis on minimizing the risk of false
      positive PCR results. The specimens analysed included synovial fluid,
      periprosthetic biopsies from the joint capsule and the interface membrane, and
      specimens from the surface of the explanted prosthesis rendered accessible by
      scraping and sonication. No antibiotics were given prior to specimen collection.
      Based on five diagnostic criteria recently suggested, we identified 18 PJIs, all
      of which fulfilled the criterion of >=2 positive cultures of periprosthetic
      specimens. The rate of culture-positive biopsies from the interface membrane was
      higher compared to specimens from the joint capsule and synovial fluid, and the
      interface membrane contained a higher bacterial load. Interpretational criteria
      were applied to differentiate a true-positive PCR from potential bacterial DNA
      contamination derived from the reagents used for DNA extraction and
      amplification. The strategy to minimize the risk of false-positive PCR results
      was successful as only two PCR results were false-positive out of 216 negative
      periprosthetic specimens. Although the PCR assays themselves were very sensitive,
      three patients with low bacterial numbers in periprosthetic specimens tested
      negative by real-time PCR. This overall lowered sensitivity is most likely due to
      the reduced specimen volume used for PCR analysis compared to culture and may
      also be due to interference from human DNA present in tissue specimens. According
      to the protocol in the present study, 16S rRNA gene real-time PCR did not
      identify more cases of septic prosthetic loosening than did culture of adequate
      periprosthetic biopsies.

PMID- 22135024
TI  - Vancomycin-resistant enterococci among clinical isolates from north-west Iran:
      identification of therapeutic surrogates.

PMID- 22135025
TI  - Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor
      prognosis.
AB  - AIMS: To evaluate the role of p53, p21 and cyclin D1 expression in patients with
      penile cancer (PC). METHODS: Paraffin-embedded tissues from PC specimens from six
      pathology departments were subjected to a central histopathological review
      performed by one pathologist. The tissue microarray technique was used for
      immunostaining which was evaluated by two independent pathologists and correlated
      with cancer-specific survival (CSS). kappa-statistics were used to assess
      interobserver variability. Uni- and multivariable Cox proportional hazards
      analysis was applied to assess the independent effects of several prognostic
      factors on CSS over a median of 32 months (IQR 6-66 months). RESULTS: Specimens
      and clinical data from 110 men treated surgically for primary PC were collected.
      p53 staining was positive in 30 and negative in 62 specimens. kappa-statistics
      showed substantial interobserver reproducibility of p53 staining evaluation
      (kappa=0.73; p<0.001). The 5-year CSS rate for the entire study cohort was 74%.
      Five-year CSS was 84% in p53-negative and 51% in p53-positive PC patients
      (p=0.003). Multivariable analysis showed p53 (HR=3.20; p=0.041) and pT-stage
      (HR=4.29; p<0.001) as independent significant prognostic factors for CSS. Cyclin
      D1 and p21 expression were not correlated with survival. However, incorporating
      p21 into a multivariable Cox model did contribute to improved model quality for
      predicting CSS. CONCLUSIONS: In patients with PC, the expression of p53 in the
      primary tumour specimen can be reproducibly assessed and is negatively associated
      with cancer specific survival.

PMID- 22135026
TI  - Twenty-year review of quantitative transmission electron microscopy for the
      diagnosis of primary ciliary dyskinesia.
AB  - BACKGROUND: The examination of ciliary ultrastructure in a nasal sample remains a
      definitive diagnostic test for primary ciliary dyskinesia (PCD). METHODS: The
      quantitative assessment of ciliary ultrastructure in the diagnosis of PCD over a
      20-year period was reviewed. RESULTS: During this period, 1182 patients were
      referred for ciliary ultrastructural analysis, 242 (20%) of whom were confirmed
      as having the disease. The two main causes of PCD identified were a lack of outer
      dynein arms (43%) and a lack of both inner and outer dynein arms (24%). Other
      causes included transposition, radial spoke and inner dynein arm defects. No
      specific ultrastructural defects were detected in 33 patients (3%) diagnosed as
      having PCD on the basis of their clinical features and screening tests that
      included a low nasal nitric oxide concentration or slow saccharine clearance and
      abnormal ciliary beat frequency or pattern. CONCLUSIONS: Electron microscopy
      analysis can confirm but does not always exclude a diagnosis of PCD.

PMID- 22135027
TI  - Role of routine neuropathological examination for determining cause of death in
      sudden unexpected deaths in infancy (SUDI).
AB  - BACKGROUND: Current guidelines for the investigation of sudden unexpected death
      in infancy (SUDI) include full neuropathological examination with recommendations
      for brain fixation for 1-2 weeks. Little evidence is available regarding the
      yield of such examination in determining cause of death in clinical practice.
      This study examines the frequency of neuropathological findings determining cause
      of death at postmortem examination in SUDI in relation to clinical and
      macroscopic features. METHODS: All postmortem examinations performed for the
      indication of SUDI at a single specialist centre over a 14-year period were
      reviewed, including clinical history, macroscopic and neuropathological findings.
      RESULTS: 6% of postmortem examinations performed for cases of SUDI demonstrated a
      neuropathological cause of death; in almost all (>90%) the clinical history
      and/or macroscopic examination suggested the cause of death. In 2% of all cases
      the cause of death was determined by histological neuropathological examination,
      but there were no cases in which histological neuropathological examination of a
      macroscopically normal brain revealed the cause of death in the absence of a
      'neurological history'. Macroscopic brain abnormalities and the presence of a
      'neurological history' were significantly more likely to yield histological brain
      abnormalities (11-fold and fourfold, respectively). CONCLUSIONS: Histological
      neuropathological examination rarely determines the cause of death in SUDI in the
      absence of macroscopic abnormalities or neurological clinical history. A
      macroscopically abnormal brain and the presence of a clinical history of possible
      neurological disease or of inflicted injury are significantly more likely to be
      associated with significant histological brain abnormalities.

PMID- 22135028
TI  - PAX8 is expressed in the majority of renal epithelial neoplasms: an
      immunohistochemical study of 223 cases using a mouse monoclonal antibody.
AB  - AIMS: PAX8 is a cell lineage-specific transcription factor which plays a crucial
      role in the organogenesis of the kidney, thyroid gland and Mullerian duct. A
      previous study showed that PAX8 is a specific and sensitive marker for both renal
      and ovarian carcinomas. The purpose of this study is to investigate PAX8
      expression using a new monoclonal PAX8 antibody in a larger number of renal
      epithelial neoplasms including clear cell renal cell carcinoma, papillary renal
      cell carcinoma, chromophobe renal cell carcinoma and renal oncocytoma. METHODS:
      PAX8 immunohistochemical staining was performed on tissue microarrays containing
      84 cases of clear cell renal cell carcinoma, 66 cases of chromophobe renal cell
      carcinoma, 57 cases of papillary renal cell carcinoma and 16 cases of renal
      oncocytoma. RESULTS: PAX8 expression was detected in 93% (78/84) of cases of
      clear cell renal cell carcinoma, 80% (53/66) of cases of chromophobe renal cell
      carcinoma, 95% (54/57) of cases of papillary renal cell carcinoma and 94% (15/16)
      of cases of renal oncocytoma. CONCLUSIONS: PAX8 is expressed in the majority of
      renal epithelial neoplasms including renal cell carcinomas and oncocytomas and
      the monoclonal PAX8 antibody is more sensitive than polyclonal antibody to detect
      chromophobe renal cell carcinoma. These results showed that PAX8 is a valuable
      marker for nephric neoplasms.

PMID- 22135029
TI  - Bile duct changes in different etiologic types of end-stage chronic liver
      disease: a study on native explant livers.
AB  - AIMS: Bile duct changes in the form of intraepithelial neoplasia or dysplasia
      have been well studied in chronic biliary tract diseases. It is important to
      analyse the morphologic spectrum of bile duct changes in non-biliary diseases as
      a link has been reported between intrahepatic cholangiocarcinoma and chronic
      liver disease associated with viral hepatitis, metabolic syndromes and with
      alcohol abuse. METHODS: The authors retrospectively reviewed liver explants of
      alcoholic liver disease (ALD)-, hepatitis C virus- and non-alcoholic fatty liver
      disease-related end-stage liver diseases to analyse morphologic changes in large
      intrahepatic bile ducts. Diagnostic criteria of biliary intraepithelial lesions
      at end-stage disease are discussed. RESULTS: Majority of explants exhibited
      reactive changes. Normal cuboidal epithelium of septal bile ducts was observed in
      minority of cases. Low-grade biliary intraepithelial neoplastic lesions were
      identified in all cases with variable frequency. None of the cases were
      associated with cholangiocarcinoma. Nuclear hyperchromasia, cellular polarity and
      presence o inflammation were considered as differentiating points between
      reactive and neoplastic lesions. CONCLUSIONS: At end stage of liver disease,
      large septal bile ducts rarely show normal morphology. Presence of low-grade
      biliary dysplasia at end stage signifies its frequent occurrence probably in
      response to alcohol/viral/metabolic syndrome-related injury. ADDITION TO
      LITERATURE: Observational analysis of large bile ducts in non-biliary diseases of
      varied aetiology has not been discussed from this part of world where incidence
      of cholangiocarcinoma is low. Identifying these lesions correctly is important.
      The frequency of these lesions is not uncommon especially at the end-stage liver
      disease.

PMID- 22135030
TI  - Self-assembly of tubular microstructures from mixed-valence metal complexes and
      their reversible transformation by external stimuli.

PMID- 22135031
TI  - Total parathyroidectomy improves survival of hemodialysis patients with secondary
      hyperparathyroidism.
AB  - BACKGROUND AND AIMS: To compare the prognosis of chronic hemodialysis patients
      with or without parathyroidectomy. METHODS: Among 158 chronic hemodialysis
      patients who underwent total parathyroidectomy between July 1998 and April 2009,
      88 patients were matched with 88 controls for sex, age, underlying disease and
      prior dialysis history. Then a retrospective evaluation of their prognosis was
      performed over a median observation period of 4.41 years. RESULTS: The overall
      survival rate was 90.4% in the parathyroidectomy group and 67.4% in the control
      group. The cardiovascular death-free survival rate was 94.6% in the
      parathyroidectomy group and 76.3% in the control group. During observation,
      intact parathyroid hormone was measured every 6 months, and its average serum
      level was 37 +/- 92 ng/L in the total parathyroidectomy group versus 274 +/- 233
      ng/L in the control group (p=0.0001). The total parathyroidectomy group had a
      significantly lower corrected calcium level and higher serum albumin level.
      Multivariate analysis revealed that parathyroidectomy, atrial fibrillation and
      serum albumin were significant factors for both total and cardiovascular
      mortality. CONCLUSION: Total parathyroidectomy was associated with better
      survival, probably due to decreased cardiovascular mortality.

PMID- 22135032
TI  - Tacrolimus versus cyclosporine for early steroid withdrawal after renal
      transplantation.
AB  - INTRODUCTION: This study compares cyclosporine (CsA) with tacrolimus (Tac) in
      preventing acute rejection (AR) after steroid withdrawal (SW) 5 days after renal
      transplantation (Tx). METHODS: The data were collected from 2 prospective
      sequential studies carried out from February 2002 to May 2006. Forty-nine
      patients received CsA, 56 patients Tac. Rapamycin (Rapa) was added to both
      calcineurin inhibitors (CNIs). The studies were homogeneous regarding both
      clinical procedures and patient demographics. RESULTS: Three years after SW, Tac
      was more effective than CsA in reducing the risk both of AR (35% vs. 53%; p<0.06)
      and mainly of relapses (9% vs. 33%; p<0.007). In addition, Tac enabled more
      patients to go onto a steroid-free regime (88% vs. 65%; p<0.01). No difference
      arose concerning the timing of AR, graft function, CNI withdrawal, incidence of
      side effects or patient and graft survival rates. In both groups, rejection after
      SW was associated with a worse graft function. CONCLUSIONS: Tac was more
      effective than CsA in preventing AR after early SW, and increased significantly
      patient probability of maintaining a steroid-free regime. In this setting, Tac
      and CsA had the same safety profile. However, a follow-up longer than 3 years
      might be needed to estimate the consequences of the higher rate of AR encountered
      under CsA therapy.

PMID- 22135033
TI  - Effect of doxazosin on expression of eNOS in rat kidney in the presence of
      partial bladder outlet obstruction.
AB  - BACKGROUND: The role of nitric oxide in the pathogenesis of renal injury has
      begun to be appreciated. We therefore designed this study to demonstrate the
      relationship between endothelial nitric oxide synthase (eNOS) expression and
      doxazosin in the kidneys of rats with surgically created partial bladder outlet
      obstruction (BOO), to further understand the role of doxazosin in the prevention
      of renal parenchymal damage by partial BOO. MATERIAL AND METHODS: A total of 35
      adult female Wistar rats, mean weight 250 g, were randomly allocated to 3
      experimental groups: group1, sham-operated (n=10); group 2, partial BOO group
      (n=14) and group 3, partial BOO group treated with doxazosin (n=11). Partial BOO
      in rats was surgically induced. Results were assessed by eNOS
      immunohistochemistry. RESULTS: eNOS staining in kidneys in group 1 (16.45 +/-
      1.63) was significantly higher than in group 2 (5.09 +/- 0.61) (p<0.05). After 15
      days of doxazosin treatment in addition to partial BOO (group 3), eNOS staining
      in the kidney (11.80 +/- 1.63) was significantly higher than in group 2 (5.09 +/-
      0.61) (p<0.05). In samples taken after 15 days of doxazosin treatment in addition
      to partial BOO, eNOS staining in kidneys (11.80 +/- 1.63) was lower than in the
      sham-operated group (16.45 +/- 1.63), but the difference was not significant
      (p>0.05). CONCLUSION: These findings may provide insight into the beneficial and
      restorative effects of alpha(1)-adrenoceptor antagonists on eNOS expression in
      the kidney, when used to treat symptoms of benign prostate hyperplasia and
      hypertension.

PMID- 22135034
TI  - A killer on the road: circulating CD4(+)CD28null T cells as cardiovascular risk
      factor in ESRD patients.
AB  - Chronic kidney disease (CKD) is associated with a sharp increase in the risk for
      cardiovascular disease, which can only be partially explained by known classical
      risk factors. However, there is a well-established association with increased
      systemic inflammation. In the last decade, an unique cytotoxic CD4(+) T cell
      population has been identified, which can be recognized by the loss of the
      costimulatory cell surface marker CD28, hence their name CD4(+)CD28null T cells.
      These cells are highly proinflammatory, have the functional features of
      professional killer lymphocytes and can expand from less than 1% to over 50% of
      the total CD4(+) T cell population. In this review, we show that these cells
      probably play an important role in destabilizing atherosclerotic plaques and
      could explain, at least in part, the association of cardiovascular disease with
      an increased inflammatory milieu in CKD patients.

PMID- 22135035
TI  - The systemic capillary leak syndrome: a scarcely known nephrological entity.
AB  - The idiopathic systemic capillary leak syndrome (SCLS) is a rare life-threatening
      disorder characterized by periodic episodes of hypovolemic shock, due to plasma
      leakage from the intravascular to the interstitial space, as reflected by
      accompanying hypoalbuminemia, hemoconcentration and edema. Here we report the
      case of a 65-year-old woman affected by SCLS who required aggressive
      resuscitation with norepinephrine, steroids, albumin and crystalloids. Then, a
      long-term prophylaxis with a beta(2)-adrenergic receptor agonist and theophylline
      was started. In conclusion, though SCLS is a rare entity, the associated
      morbidity and mortality require the physician's awareness to provide timely
      therapy. Underrecognition in the medical community and rarity of this syndrome
      have precluded analysis by rational clinical trial designs that are necessary to
      determine more targeted and adequate therapy. This report is meant to enhance
      awareness of SCLS in the nephrology community.

PMID- 22135036
TI  - The correlation of hip fracture and hyponatremia in the elderly.
AB  - BACKGROUND: Increasing age is considered one of the risk factors for
      hyponatremia. The concept of asymptomatic hyponatremia is not correct anymore as
      these patients have a greater risk for falls, bone fractures and attention
      impairment. The combination of old age and a fall is a common recipe for
      admission to a nursing home. METHODS: We identified 249 patients 65 years of age
      or older who were admitted to hospital with the diagnosis of hip fracture
      secondary to fall, during a 3-year period. We compared their serum Na level on
      admission with that of controls: 44 ambulatory patients admitted for elective hip
      or knee replacement surgery during the same time frame. Odds ratios (ORs) were
      calculated using logistic regression. RESULTS: The prevalence of hyponatremia in
      cases was 16.9%, versus 4.6% in controls (p=0.03). Age and hyponatremia were
      strongly correlated with hip fracture secondary to fall. The univariate OR for
      hip fracture associated with each 10-year increase in age was 5.57 (p<0.0001).
      After controlling for age, cases were almost 5 times as likely as controls to be
      hyponatremic (OR=4.80, p=0.04). CONCLUSIONS: Even mild hyponatremia in the
      elderly should be considered a risk factor for falls. Correction of hyponatremia
      in the elderly may reduce morbidity and mortality, and at the same time, it has a
      huge impact on socioeconomic status.

PMID- 22135037
TI  - Novel Cbeta-Cgamma bond cleavages of tryptophan-containing peptide radical
      cations.
AB  - In this study, we observed unprecedented cleavages of the C(beta)-C(gamma) bonds
      of tryptophan residue side chains in a series of hydrogen-deficient tryptophan
      containing peptide radical cations (M(*+)) during low-energy collision-induced
      dissociation (CID). We used CID experiments and theoretical density functional
      theory (DFT) calculations to study the mechanism of this bond cleavage, which
      forms [M - 116](+) ions. The formation of an alpha-carbon radical intermediate at
      the tryptophan residue for the subsequent C(beta)-C(gamma) bond cleavage is
      analogous to that occurring at leucine residues, producing the same product ions;
      this hypothesis was supported by the identical product ion spectra of [LGGGH -
      43](+) and [WGGGH - 116](+), obtained from the CID of [LGGGH](*+) and
      [WGGGH](*+), respectively. Elimination of the neutral 116-Da radical requires
      inevitable dehydrogenation of the indole nitrogen atom, leaving the radical
      centered formally on the indole nitrogen atom ([Ind](*)-2), in agreement with the
      CID data for [WGGGH](*+) and [W(1-CH3)GGGH](*+); replacing the tryptophan residue
      with a 1-methyltryptophan residue results in a change of the base peak from that
      arising from a neutral radical loss (116 Da) to that arising from a molecule loss
      (131 Da), both originating from C(beta)-C(gamma) bond cleavage. Hydrogen atom
      transfer or proton transfer to the gamma-carbon atom of the tryptophan residue
      weakens the C(beta)-C(gamma) bond and, therefore, decreases the dissociation
      energy barrier dramatically.

PMID- 22135038
TI  - Evaluation of a sophisticated SCFG design for RNA secondary structure prediction.
AB  - Predicting secondary structures of RNA molecules is one of the fundamental
      problems of and thus a challenging task in computational structural biology. Over
      the past decades, mainly two different approaches have been considered to compute
      predictions of RNA secondary structures from a single sequence: the first one
      relies on physics-based and the other on probabilistic RNA models. Particularly,
      the free energy minimization (MFE) approach is usually considered the most
      popular and successful method. Moreover, based on the paradigm-shifting work by
      McCaskill which proposes the computation of partition functions (PFs) and base
      pair probabilities based on thermodynamics, several extended partition function
      algorithms, statistical sampling methods and clustering techniques have been
      invented over the last years. However, the accuracy of the corresponding
      algorithms is limited by the quality of underlying physics-based models, which
      include a vast number of thermodynamic parameters and are still incomplete. The
      competing probabilistic approach is based on stochastic context-free grammars
      (SCFGs) or corresponding generalizations, like conditional log-linear models
      (CLLMs). These methods abstract from free energies and instead try to learn about
      the structural behavior of the molecules by learning (a manageable number of)
      probabilistic parameters from trusted RNA structure databases. In this work, we
      introduce and evaluate a sophisticated SCFG design that mirrors state-of-the-art
      physics-based RNA structure prediction procedures by distinguishing between all
      features of RNA that imply different energy rules. This SCFG actually serves as
      the foundation for a statistical sampling algorithm for RNA secondary structures
      of a single sequence that represents a probabilistic counterpart to the sampling
      extension of the PF approach. Furthermore, some new ways to derive meaningful
      structure predictions from generated sample sets are presented. They are used to
      compare the predictive accuracy of our model to that of other probabilistic and
      energy-based prediction methods. Particularly, comparisons to lightweight SCFGs
      and corresponding CLLMs for RNA structure prediction indicate that more complex
      SCFG designs might yield higher accuracy but eventually require more
      comprehensive and pure training sets. Investigations on both the accuracies of
      predicted foldings and the overall quality of generated sample sets (especially
      on an abstraction level, called abstract shapes of generated structures, that is
      relevant for biologists) yield the conclusion that the Boltzmann distribution of
      the PF sampling approach is more centered than the ensemble distribution induced
      by the sophisticated SCFG model, which implies a greater structural diversity
      within generated samples. In general, neither of the two distinct ensemble
      distributions is more adequate than the other and the corresponding results
      obtained by statistical sampling can be expected to bare fundamental differences,
      such that the method to be preferred for a particular input sequence strongly
      depends on the considered RNA type.

PMID- 22135039
TI  - Stereochemical studies of the type II isopentenyl diphosphate-dimethylallyl
      diphosphate isomerase implicate the FMN coenzyme in substrate protonation.

PMID- 22135040
TI  - Specific absorption rate benefits of including measured electric field
      interactions in parallel excitation pulse design.
AB  - Specific absorption rate management and excitation fidelity are key aspects of
      radiofrequency pulse design for parallel transmission at ultra-high magnetic
      field strength. The design of radiofrequency pulses for multiple channels is
      often based on the solution of regularized least-squares optimization problems
      for which a regularization term is typically selected to control the integrated
      or peak pulse waveform amplitude. Unlike single-channel transmission, the
      specific absorption rate of parallel transmission is significantly influenced by
      interferences between the electric fields associated with the individual
      transmission elements, which a conventional regularization term does not take
      into account. This work explores the effects upon specific absorption rate of
      incorporating experimentally measurable electric field interactions into parallel
      transmission pulse design. Results of numerical simulations and phantom
      experiments show that the global specific absorption rate during parallel
      transmission decreases when electric field interactions are incorporated into
      pulse design optimization. The results also show that knowledge of electric field
      interactions enables robust prediction of the net power delivered to the sample
      or subject by parallel radiofrequency pulses before they are played out on a
      scanner.

PMID- 22135041
TI  - Spectroscopic imaging with prospective motion correction and retrospective phase
      correction.
AB  - Motion-induced artifacts are much harder to recognize in magnetic resonance
      spectroscopic imaging than in imaging experiments and can therefore lead to
      erroneous interpretation. A method for prospective motion correction based on an
      optical tracking system has recently been proposed and has already been
      successfully applied to single voxel spectroscopy. In this work, the utility of
      prospective motion correction in combination with retrospective phase correction
      is evaluated for spectroscopic imaging in the human brain. Retrospective phase
      correction, based on the interleaved reference scan method, is used to correct
      for motion-induced frequency shifts and ensure correct phasing of the spectra
      across the whole spectroscopic imaging slice. It is demonstrated that the
      presented correction methodology can reduce motion-induced degradation of
      spectroscopic imaging data.

PMID- 22135042
TI  - Diagnosis and treatment of minimal hepatic encephalopathy to prevent motor
      vehicle accidents: a cost-effectiveness analysis.
AB  - Minimal hepatic encephalopathy (MHE) in cirrhosis is associated with impaired
      driving skills and increased risk of motor vehicle accidents (MVAs). Detection
      and treatment of MHE has the potential to reduce costs and morbidity associated
      with MVAs. We conducted a cost-effectiveness analysis to assess the benefits of
      different strategies of MHE diagnosis and treatment for reducing MVA-related
      societal costs. The analyses compared five MHE management strategies: (1)
      presumptive treatment of all cirrhosis patients; (2) diagnosis by
      neuropsychological exam (NPE) with treatment; (3) diagnosis by standard
      psychometric tests (SPTs) with treatment; (4) diagnosis by rapid screening using
      inhibitory control test (ICT) with treatment; and (5) no MHE diagnosis or
      treatment (status quo). Treatments considered were lactulose or rifaximin, which
      were assumed to reduce the MVA rate to the level of similarly aged noncirrhosis
      patients with benefit adjusted for treatment compliance. A Markov model followed
      a simulated cohort of 1,000 cirrhosis patients without overt hepatic
      encephalopathy (OHE), from entry into treatment, through MHE development, and
      later OHE, when they exited the modeled cohort. Follow-up was for 5 years and
      included biannual MHE testing. The societal cost of a single MVA was estimated at
      $42,100. All four strategies with lactulose were cost-saving compared with the
      status quo. Diagnosis with ICT and lactulose was the most cost-effective approach
      (cost/MVA prevented: $24,454 ICT; $25,470 SPT; $30,469 presumptive treatment and
      $33,742 NPE). Net program savings over 5 years ranged from $1.7 to 3.6 million
      depending on the strategy. Rifaximin therapy was not cost-saving at current
      prices but would become so at a monthly cost of <$353. CONCLUSION: Detection of
      MHE, especially using the ICT, and subsequent treatment with lactulose could
      substantially reduce societal costs by preventing MVAs.

PMID- 22135043
TI  - Immunomodulation of curcumin on adoptive therapy with T cell functional imaging
      in mice.
AB  - Adoptive T-cell therapy involves the ex vivo expansion and subsequent transfusion
      of tumor-specific T lymphocytes to eliminate tumors. Using immune modulators to
      block immunosuppressive factors in the tumor microenvironment has emerged as a
      promising strategy to enhance T-cell-mediated tumor regression. Curcumin, a major
      component of turmeric, has been shown to possess antitumor and immunomodulatory
      effects by regulating a diverse range of molecular targets. Thus, we hypothesize
      that these beneficial effects of curcumin may improve the therapeutic efficacy of
      adoptive therapy. Here, we have shown that curcumin enhances cytotoxicity of
      CD8(+) T cells toward tumors via alteration of the tumor microenvironment when
      combined with adoptive therapy. We found that T-cell accumulation and function
      were increased in combined treatment due to the blockade of different
      immunosuppressors, including TGF-beta, indoleamine 2,3-dioxygenase, and
      regulatory T cells. Furthermore, bioluminescent imaging with a granzyme B
      promoter-conjugated optical reporter also reflected improved cytotoxicity of
      antigen-specific CD8(+) T cells in tumor-bearing mice during treatment. These
      findings suggest that combination of multitargeting drugs, such as curcumin, with
      adoptive therapy may have potential for clinical application. In addition, using
      a granzyme B-specific imaging reporter to assess T-cell function may also be
      applied for the development and therapeutic evaluation of new immunotherapy in
      preclinical studies.

PMID- 22135045
TI  - DNA methylation of phosphatase and actin regulator 3 detects colorectal cancer in
      stool and complements FIT.
AB  - Using a bioinformatics-based strategy, we set out to identify hypermethylated
      genes that could serve as biomarkers for early detection of colorectal cancer
      (CRC) in stool. In addition, the complementary value to a Fecal Immunochemical
      Test (FIT) was evaluated. Candidate genes were selected by applying cluster
      alignment and computational analysis of promoter regions to microarray-expression
      data of colorectal adenomas and carcinomas. DNA methylation was measured by
      quantitative methylation-specific PCR on 34 normal colon mucosa, 71 advanced
      adenoma, and 64 CRC tissues. The performance as biomarker was tested in whole
      stool samples from in total 193 subjects, including 19 with advanced adenoma and
      66 with CRC. For a large proportion of these series, methylation data for GATA4
      and OSMR were available for comparison. The complementary value to FIT was
      measured in stool subsamples from 92 subjects including 44 with advanced adenoma
      or CRC. Phosphatase and Actin Regulator 3 (PHACTR3) was identified as a novel
      hypermethylated gene showing more than 70-fold increased DNA methylation levels
      in advanced neoplasia compared with normal colon mucosa. In a stool training set,
      PHACTR3 methylation showed a sensitivity of 55% (95% CI: 33-75) for CRC and a
      specificity of 95% (95% CI: 87-98). In a stool validation set, sensitivity
      reached 66% (95% CI: 50-79) for CRC and 32% (95% CI: 14-57) for advanced adenomas
      at a specificity of 100% (95% CI: 86-100). Adding PHACTR3 methylation to FIT
      increased sensitivity for CRC up to 15%. PHACTR3 is a new hypermethylated gene in
      CRC with a good performance in stool DNA testing and has complementary value to
      FIT.

PMID- 22135044
TI  - Oral contraceptives decrease the prevalence of ovarian cancer in the hen.
AB  - Ovarian cancer is the leading cause of reproductive cancer death in U.S. women.
      This high mortality rate is due to the lack of early detection methods and
      ineffectiveness of therapy for advanced disease. Until more effective screening
      methods and therapies are developed, chemoprevention strategies are warranted.
      The hen has a high spontaneous prevalence of ovarian cancer and has been used as
      a model for studying ovarian cancer chemoprevention. In this study, we used the
      hen to determine the effect of progestin alone, estrogen alone, or progestin and
      estrogen in combination (as found in oral contraceptives) on ovarian cancer
      prevalence. We found that treatment with progestin alone and in combination with
      estrogen decreased the prevalence of ovarian cancer. A significant risk reduction
      of 91% was observed in the group treated with progestin alone (risk ratio =
      0.0909; 95% CI: 0.0117-0.704) and an 81% reduction was observed in the group
      treated with progestin plus estrogen (risk ratio = 0.1916; 95% CI = 0.043-0.864).
      Egg production was also significantly reduced in these treatment groups compared
      with control. We found no effect of progestin, either alone or in combination
      with estrogen, on apoptosis or proliferation in the ovary, indicating that this
      is not the likely mechanism responsible for the protective effect of progestin in
      the hen. Our results support the use of oral contraceptives to prevent ovarian
      cancer and suggest that ovulation is related to the risk of ovarian cancer in
      hens and that other factors, such as hormones, more than likely modify this risk.

PMID- 22135046
TI  - The effect of HIV and HPV coinfection on cervical COX-2 expression and systemic
      prostaglandin E2 levels.
AB  - Human immunodeficiency virus (HIV-1) infection causes chronic inflammation. COX-2
      derived prostaglandin E(2) (PGE(2)) has been linked to both inflammation and
      carcinogenesis. We hypothesized that HIV-1 could induce COX-2 in cervical tissue
      and increase systemic PGE(2) levels and that these alterations could play a role
      in AIDS-related cervical cancer. Levels of cervical COX-2 mRNA and urinary PGE-M,
      a biomarker of systemic PGE(2) levels, were determined in 17 HIV-negative women
      with a negative cervical human papilloma virus (HPV) test, 18 HIV-infected women
      with a negative HPV test, and 13 HIV-infected women with cervical HPV and high
      grade squamous intraepithelial lesions on cytology. Cervical COX-2 levels were
      significantly associated with HIV and HPV status (P = 0.006 and 0.002,
      respectively). Median levels of urinary PGE-M were increased in HIV-infected
      compared with uninfected women (11.2 vs. 6.8 ng/mg creatinine, P = 0.02). Among
      HIV-infected women, urinary PGE-M levels were positively correlated with plasma
      HIV-1 RNA levels (P = 0.003). Finally, levels of cervical COX-2 correlated with
      urinary PGE-M levels (P = 0.005). This study shows that HIV-1 infection is
      associated with increased cervical COX-2 and elevated systemic PGE(2) levels.
      Drugs that inhibit the synthesis of PGE(2) may prove useful in reducing the risk
      of cervical cancer or systemic inflammation in HIV-infected women.

PMID- 22135048
TI  - Randomized phase II trial of lyophilized strawberries in patients with dysplastic
      precancerous lesions of the esophagus.
AB  - Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC).
      We previously showed that dietary freeze-dried, or lyophilized, strawberry powder
      inhibits N-nitrosomethylbenzylamine-induced SCC in the rat esophagus. On the
      basis of this observation, we conducted a randomized (noncomparative) phase II
      trial in China to investigate the effects of two doses of freeze-dried
      strawberries in patients with esophageal dysplastic lesions in a high-risk area
      for esophageal cancer. We randomly assigned 75 patients identified by endoscopy
      to have dysplastic esophageal premalignant lesions to receive freeze-dried
      strawberry powder at either 30 g/d (37 patients) or 60 g/d (38 patients) for six
      months; the powder was mixed with water and drunk. After six months, we assessed
      the changes in histologic grade of these lesions (primary endpoint) in a blinded
      fashion. The dose of 30 g/d, did not significantly affect histology or any other
      measured parameter. The dose of 60 g/d, however, reduced the histologic grade of
      dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who
      were evaluated for histology (P < 0.0001). The strawberry powder was well
      tolerated, with no toxic effects or serious adverse events. Strawberries (60 g/d)
      also reduced protein expression levels of inducible nitric oxide synthase (iNOS)
      by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phospho
      nuclear factor kappa B (NFkappaB)-p65 (pNFkappaB-p65) by 62.6% (P < 0.001), and
      phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 g/d) also
      significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our
      present results indicate the potential of freeze-dried strawberry powder for
      preventing human esophageal cancer, supporting further clinical testing of this
      natural agent in this setting.

PMID- 22135047
TI  - Nuclear receptors as modulators of the tumor microenvironment.
AB  - Over the past several decades of cancer research, the inherent complexity of
      tumors has become increasingly appreciated. In addition to acquired cell
      intrinsic properties, tumor initiation and growth is supported by an abundance of
      parenchymal, inflammatory, and stromal cell types, which infiltrate and surround
      the tumor. Accumulating evidence shows that numerous components of this
      supportive milieu, referred to collectively as the tumor microenvironment, are
      indeed critical during the process of multistep tumorigenesis. These findings
      highlight the important interplay between neoplastic cells and tumor-associated
      cell types, and suggest that therapy should target both neoplastic cells and
      supportive stromal cells to effectively attenuate tumor growth. The nuclear
      receptor superfamily encompasses a druggable class of molecules expressed in
      numerous stromal and parenchymal cell types, whose established physiologic roles
      suggest their potential as therapeutic and preventive targets in the context of
      the reactive tumor microenvironment. In this minireview, we discuss recent
      evidence that tumor-associated inflammation, angiogenesis, and fibrosis can be
      modulated at the transcriptional level by nuclear receptors and their ligands. As
      these processes have been widely implicated in cancer initiation, progression,
      and resistance to current therapy, nuclear receptor ligands targeting the tumor
      microenvironment may be potent antitumor agents in combination therapies,
      including for preventing cancer development within high-risk populations.

PMID- 22135049
TI  - Synthesis of cyclic sulfites from epoxides and sulfur dioxide with silica
      immobilized homogeneous catalysts.
AB  - Quaternary ammonium- and amino-functionalized silica catalysts have been prepared
      for the selective synthesis of cyclic sulfites from epoxides and sulfur dioxide,
      demonstrating the effects of immobilizing the homogeneous catalysts on silica.
      The cycloaddition of sulfur dioxide to various epoxides was conducted under
      solvent-free conditions at 100  degrees C. The quaternary ammonium- and amino
      functionalized silica catalysts produced cyclic sulfites in high yields (79-96 %)
      that are comparable to those produced by the homogeneous catalysts. The
      functionalized silica catalysts could be separated from the product solution by
      filtration, thereby avoiding the catalytic decomposition of the cyclic sulfite
      products upon distillation of the product solution. Heterogenization of a
      homogeneous catalyst by immobilization can, therefore, improve the efficiency of
      the purification of crude reaction products. Despite a decrease in catalytic
      activity after each recycling step, the heterogeneous pyridine-functionalized
      silica catalyst provided high yields after as many as five recycling processes.

PMID- 22135050
TI  - Direct 3D visualization of the phase-separated morphology in chlorinated
      polyethylene/nylon terpolyamide based thermoplastic elastomers.
AB  - Blends of chlorinated polyethylene and nylon-6/-6,6/-12 terpolyamide were
      prepared. The ratio of the two components was systematically varied within the
      blends. The mechanical behavior of the samples was analyzed with tensile tests
      and dynamical mechanical analysis showing that, for several ratios, materials
      with improved mechanical properties typical of thermoplastic elastomers were
      obtained. In such a mechanical regime, a co-continuous phase-separated morphology
      was clearly evidenced at the microscopic scale by 3D laser scanning confocal
      fluorescent microscopy (LSCFM). At blend compositions where plastic tensile
      behavior is observed, LSCFM reveals dispersed spheres of one component in the
      other. 

PMID- 22135051
TI  - Magnetoresistance switch effect of a Sn-doped Bi2 Te3 topological insulator.

PMID- 22135052
TI  - Should clinical pharmacokinetic bridging studies between Caucasian and Asian
      populations be required for approval of monoclonal antibodies?

PMID- 22135053
TI  - FDA approves first stem-cell therapy.

PMID- 22135054
TI  - Medical groups, researchers fine-tune clopidogrel therapy.

PMID- 22135055
TI  - Targeted drug therapy remains a challenge.

PMID- 22135058
TI  - Ensuring safe and economical use of elastomeric infusion devices.

PMID- 22135057
TI  - Ensuring safe and economical use of elastomeric infusion devices.

PMID- 22135059
TI  - Prescribing authority for pharmacists.

PMID- 22135060
TI  - Dalfampridine: a new agent for symptomatic management of multiple sclerosis.
AB  - PURPOSE The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage,
      and place in therapy of dalfampridine are reviewed. SUMMARY Dalfampridine is a
      novel drug with a unique mechanism for the symptomatic management of multiple
      sclerosis (MS) among all classifications. Dalfampridine was approved in January
      2010 to improve walking for patients with MS. Dalfampridine blocks potassium
      channels on demyelinated neurons and allows normal electrical conduction, thus
      improving locomotor difficulty. Dalfampridine is rapidly absorbed after oral
      administration, reaching its peak plasma concentration in 1.3 hours.
      Approximately 95.9% of dalfampridine and its metabolites (3-hydroxy-4
      aminopyridine and 3- hydroxy-4-aminopyridine sulfate) is excreted in the urine.
      Dalfampridine is not an inhibitor or inducer of a major cytochrome P-450
      isoenzyme; therefore, the potential for drug-drug interactions is minimal.
      Clinical studies have shown dalfampridine to improve walking speed. The dosage of
      dalfampridine varied in clinical trials, but the recommended dosage is 10 mg
      orally twice daily. Dalfampridine is not appropriate for patients with seizures
      or moderate-to-severe renal impairment. Phase III studies found that extended
      release fampridine 10 mg twice daily is well tolerated. The most frequent adverse
      events reported in dalfampridine clinical trials were insomnia, dizziness,
      headache, nausea, and weakness. The Food and Drug Administration has required the
      manufacturer to have a risk evaluation and mitigation strategy for dalfampridine.
      Ongoing trials will determine the long-term benefit of dalfampridine. CONCLUSION
      Dalfampridine is a potassium channel blocker that has demonstrated efficacy for
      improving the symptoms of MS. Several studies have demonstrated increased walking
      speed in patients, though high doses should be avoided due to the risk of
      seizures.

PMID- 22135061
TI  - Advanced-practice pharmacists: practice characteristics and reimbursement of
      pharmacists certified for collaborative clinical practice in New Mexico and North
      Carolina.
AB  - PURPOSE The results of a survey assessing the practice settings, clinical
      activities, and reimbursement experiences of pharmacists with advanced-practice
      designations are reported. METHODS A questionnaire was sent to all certified
      Pharmacist Clinicians in New Mexico and all Clinical Pharmacist Practitioners in
      North Carolina (a total of 189 pharmacists at the time of the survey in late
      2008) to elicit information on practice settings, billing and reimbursement
      methods, collaborative drug therapy management (CDTM) protocols, and other
      issues. RESULTS Of the 189 targeted pharmacists, 64 (34%) responded to the
      survey. On average, the reported interval from pharmacist licensure to
      certification as an advanced practitioner was 11 years. The majority of survey
      participants were practicing in community or institutional settings, most often
      hospital clinics or physician offices. About two thirds of the respondents
      indicated that their employer handled the billing of their services using
      standard evaluation and management codes, with estimated total monthly billings
      averaging $6500. At the time of the survey, about 80% of the respondents were
      engaged in a CDTM protocol. The survey results suggest that pharmacists with
      advanced-practice designations are perceived favorably by patients and physicians
      and their services are in high demand, but more than one third of respondents
      indicated a need to justify their advanced-practice positions to administrators.
      CONCLUSION Pharmacists with advanced-practice designations are providing clinical
      services in various settings under collaborative practice arrangements that
      include prescribing privileges. Despite growing patient and physician acceptance,
      reimbursement challenges continue to be a barrier to wider use of CDTM programs.

PMID- 22135062
TI  - Pharmacist prescribing: what are the next steps?

PMID- 22135065
TI  - FXR protects lung from lipopolysaccharide-induced acute injury.
AB  - Acute lung injury and its more severe form, acute respiratory distress syndrome,
      are characterized by an acute inflammatory response in the airspaces and lung
      parenchyma. The nuclear receptor farnesoid X receptor (FXR) is expressed in
      pulmonary artery endothelial cells. Here, we report a protective role of FXR in a
      lipopolysaccharide-induced mouse model of acute lung injury. Upon intratracheal
      injection of lipopolysaccharide, FXR-/- mice showed higher lung endothelial
      permeability, released more bronchoalveolar lavage cells to the alveoli, and
      developed acute pneumonia. Cell adhesion molecules were expressed at higher
      levels in FXR-/- mice as compared with control mice. Furthermore, lung
      regeneration was much slower in FXR-/- mice. In vitro experiments showed that FXR
      activation blocked TNFalpha-induced expression of P-selectin but stimulated
      proliferation of lung microvascular endothelial cells through up-regulation of
      Foxm1b. In addition, expression of a constitutively active FXR repressed the
      expression of proinflammatory genes and improved lung permeability and lung
      regeneration in FXR-/- mice. This study demonstrates a critical role of FXR in
      suppressing the inflammatory response in lung and promoting lung repair after
      injury.

PMID- 22135066
TI  - An essential role for Pax8 in the transcriptional regulation of cadherin-16 in
      thyroid cells.
AB  - Cadherin-16 was originally identified as a tissue-specific cadherin present
      exclusively in kidney. Only recently, Cadherin-16 has been detected also on the
      plasma membrane of mouse thyrocytes. This last finding prompted us to note that
      the expression profile of Cadherin-16 resembles that of the transcription factor
      Pax8, a member of the Pax (paired-box) gene family, predominantly expressed in
      the developing and adult kidney and thyroid. Pax8 has been extensively
      characterized in the thyroid and shown to be a master gene for thyroid
      development and differentiation. In this study, we determined the role of the
      transcription factor Pax8 in the regulation of Cadherin-16 expression. We
      demonstrate that the Cadherin-16 minimal promoter is transcriptionally active in
      thyroid cells as well as in kidney cells, that Pax8 is able to activate
      transcription from a Cadherin-16 promoter reporter construct, and more
      importantly, that indeed Pax8 is able to bind in vivo the Cadherin-16 promoter
      region. In addition, by means of Pax8 RNA interference in thyroid cells and by
      analyzing Pax8 null mice, we demonstrate that Pax8 regulates also in vivo the
      expression of Cadherin-16. Finally, we reveal that the expression of Cadherin-16
      is TSH dependent in FRTL-5 thyroid cells and significantly reduced in mouse
      thyroid carcinomas. Therefore, we conclude that Cadherin-16 is a novel downstream
      target of the transcription factor Pax8, likely since the early steps of thyroid
      development, and that its expression is associated with the fully differentiated
      state of the thyroid cell.

PMID- 22135069
TI  - Updated ESC Guidelines for managing patients with suspected non-ST-elevation
      acute coronary syndromes.

PMID- 22135067
TI  - The expression and role of hyperpolarization-activated and cyclic nucleotide
      gated channels in endocrine anterior pituitary cells.
AB  - Pituitary cells fire action potentials independently of external stimuli, and
      such spontaneous electrical activity is modulated by a large variety of
      hypothalamic and intrapituitary agonists. Here, we focused on the potential role
      of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels in
      electrical activity of cultured rat anterior pituitary cells. Quantitative RT-PCR
      analysis showed higher level of expression of mRNA transcripts for HCN2 and HCN3
      subunits and lower expression of HCN1 and HCN4 subunits in these cells. Western
      immunoblot analysis of lysates from normal and GH(3) immortalized pituitary cells
      showed bands with appropriate molecular weights for HCN2, HCN3, and HCN4.
      Electrophysiological experiments showed the presence of a slowly developing
      hyperpolarization-activated inward current, which was blocked by Cs(+) and
      ZD7288, in gonadotrophs, thyrotrophs, somatotrophs, and a fraction of
      lactotrophs, as well as in other unidentified pituitary cell types. Stimulation
      of adenylyl cyclase and addition of 8-Br-cAMP enhanced this current and
      depolarized the cell membrane, whereas 8-Br-cGMP did not alter the current and
      hyperpolarized the cell membrane. Both inhibition of basal adenylyl cyclase
      activity and stimulation of phospholipase C signaling pathway inhibited this
      current. Inhibition of HCN channels affected the frequency of firing but did not
      abolish spontaneous electrical activity. These experiments indicate that cAMP and
      cGMP have opposite effects on the excitability of endocrine pituitary cells, that
      basal cAMP production in cultured cells is sufficient to integrate the majority
      of HCN channels in electrical activity, and that depletion of
      phosphatidylinositol 4,5-bisphosphate caused by activation of phospholipase C
      silences them.

PMID- 22135068
TI  - Suppressed prostate epithelial development with impaired branching morphogenesis
      in mice lacking stromal fibromuscular androgen receptor.
AB  - Using the cre-loxP system, we generated a new mouse model [double stromal
      androgen receptor knockout (dARKO)] with selectively deleted androgen receptor
      (AR) in both stromal fibroblasts and smooth muscle cells, and found the size of
      the anterior prostate (AP) lobes was significantly reduced as compared with those
      from wild-type littermate controls. The reduction in prostate size of the dARKO
      mouse was accompanied by impaired branching morphogenesis and partial loss of the
      infolding glandular structure. Further dissection found decreased proliferation
      and increased apoptosis of the prostate epithelium in the dARKO mouse AP. These
      phenotype changes were further confirmed with newly established immortalized
      prostate stromal cells (PrSC) from wild-type and dARKO mice. Mechanistically, IGF
      1, placental growth factor, and secreted phosphoprotein-1 controlled by stromal
      AR were differentially expressed in PrSC-wt and PrSC-ARKO. Moreover, the
      conditioned media (CM) from PrSC-wt promoted prostate epithelium growth
      significantly as compared with CM from PrSC-dARKO. Finally, adding IGF
      1/placental growth factor recombinant proteins into PrSC-dARKO CM was able to
      partially rescue epithelium growth. Together, our data concluded that stromal
      fibromuscular AR could modulate epithelium growth and maintain cellular
      homeostasis through identified growth factors.

PMID- 22135070
TI  - Letter by Weimar and Knipp regarding article, "Patients with severe asymptomatic
      carotid artery stenosis do not have a higher risk of stroke and mortality after
      coronary artery bypass surgery".

PMID- 22135071
TI  - Influence of the arterial input function on absolute and relative perfusion
      weighted imaging penumbral flow detection: a validation with 15O-water positron
      emission tomography.
AB  - BACKGROUND AND PURPOSE: Perfusion-weighted imaging maps are used to identify
      critical hypoperfusion in acute stroke. However, quantification of perfusion may
      depend on the choice of the arterial input function (AIF). Using quantitative
      positron emission tomography we evaluated the influence of the AIF location on
      maps of absolute and relative perfusion-weighted imaging to detect penumbral flow
      (PF; <20 mL/100 g/min on positron emission tomography(CBF)) in acute stroke.
      METHODS: In 22 patients with acute stroke the AIF was placed at 7 sites (M1, M2,
      M3 ipsi- and contralateral and internal carotid artery-M1 contralateral to the
      infarct). Comparative (15)O-water positron emission tomography and AIF-dependent
      perfusion-weighted imaging (cerebral blood flow, cerebral blood volume, mean
      transit time, and time to maximum) were performed. A receiver operating
      characteristic curve analysis described the threshold independent performance
      (area under the curve) of the perfusion-weighted maps for all 7 AIF locations and
      identified the best AIF-dependent absolute and relative thresholds to identify
      PF. These results were compared with AIF-independent time-to-peak maps. RESULTS:
      Quantitative perfusion-weighted imaging maps of cerebral blood flow and time to
      maximum performed best. For PF detection, AIF placement did significantly
      influence absolute PF thresholds. However, AIF placement did not influence (1)
      the threshold independent performance; and (2) the relative PF thresholds. AIF
      placement in the proximal segment of the contralateral middle cerebral artery
      (cM1) was preferable for quantification. CONCLUSIONS: AIF-based maps of cerebral
      blood flow and time to maximum were most accurate to detect the PF threshold. The
      AIF placement significantly altered absolute PF thresholds and showed best
      agreement with positron emission tomography for the cM1 segment. The performance
      of relative PF thresholds, however, was not AIF location-dependent and might be
      along with AIF-independent time-to-peak maps, more suitable than absolute PF
      thresholds in acute stroke if detailed postprocessing is not feasible.

PMID- 22135072
TI  - Predictors of tissue-type plasminogen activator nonresponders according to
      location of vessel occlusion.
AB  - BACKGROUND AND PURPOSE: Information on the clinical and hemodynamic profile of
      intravenous tissue-type plasminogen activator nonresponders, at different
      locations of arterial occlusion, may improve the selection of candidates for
      rescue reperfusion therapies. Therefore, we aim to investigate predictors of
      failing intravenous tissue-type plasminogen activator therapy according to
      occluded vessel and location of the clot. METHODS: We prospectively evaluated
      consecutive patients with an acute ischemic stroke admitted within the first 6
      hours of onset. Five hundred forty-eight patients with documented intracranial
      occlusion were included. Patients were categorized according to site of vessel
      occlusion into 4 distinct groups: proximal middle cerebral artery occlusion
      (n=251), distal middle cerebral artery occlusion (n=194), internal carotid artery
      bifurcation occlusion (n=61), and basilar artery occlusion (n=42). Recanalization
      was assessed on transcranial Doppler at 1 hour of tissue-type plasminogen
      activator bolus. RESULTS: Among patients with proximal middle cerebral artery
      occlusion, the presence of severe extracranial internal carotid artery stenosis
      or occlusion (OR, 2.36; 95% CI, 1.15-4.84; P=0.02) and age >74 years (OR, 1.84;
      95% CI, 1.02-3.31; P=0.04) independently predicted no recanalization. No
      independent predictors of no recanalization were identified in patients with
      distal middle cerebral artery occlusion. In patients with internal carotid artery
      bifurcation occlusion, a previous diagnosis of hypertension (OR, 12.77; 95% CI,
      2.12-76.88; P=0.05), and absence of atrial fibrillation (OR, 8.15; 95% CI, 1.40
      47.44; P=0.02) emerged as independent predictors of no recanalization. Similarly,
      among patients with basilar artery occlusion, absence of atrial fibrillation was
      as an independent predictor of no recanalization (OR, 7.50; 95% CI, 1.40-40.35;
      P=0.02). CONCLUSIONS: The use of relevant predictors of no recanalization and a
      rapid neurovascular evaluation may improve the selection of patients for more
      aggressive rescue strategies.

PMID- 22135073
TI  - Intravenous thrombolysis for stroke increases over time at primary stroke
      centers.
AB  - BACKGROUND AND PURPOSE: We evaluated the impact that duration as a primary stroke
      center (PSC) had on tissue-type plasminogen activator (tPA) utilization for acute
      ischemic stroke. METHODS: A retrospective analysis of the Illinois Hospital
      Association CompData was performed identifying those patients with primary
      discharge diagnosis of acute ischemic stroke based on International
      Classification of Diseases version 9 codes. We assessed utilization of tPA by
      International Classification of Diseases version 9 procedure code (99.10). We
      categorized patients as cared for at non-PSC, PSC >1 year before, <=1 year
      before, <=1 year after, and >1 year after certification. We used generalized
      estimating equations to calculate adjusted odds ratios for tPA utilization by PSC
      category. RESULTS: Among 119,539 acute ischemic stroke patients (mean age, 72
      years; 55.2% women), tPA use was 1.9% but increased by PSC category (P<0.001):
      (1) non-PSC 0.9%; (2) >1 year before PSC certification 1.4%; (3) <=1 year before
      certification 3.2%; (4) <=1 year after certification 4.3%; and (5) >1 year after
      certification 6.5%. Adjusting for age, insurance status, admission source, year
      of study, region of Illinois, and hospital bed size, the odds of tPA utilization
      increased with advancing stage of PSC certification (highest category: adjusted
      odds ratio, 2.37; 95% confidence interval, 1.52-3.71). CONCLUSIONS: Although
      increasing over time, stroke thrombolysis is strongly impacted by the PSC
      certification process. Rather than waning or stagnating, tPA utilization
      increases at PSC from the earliest phases of preparation through certification
      and subsequent maintenance.

PMID- 22135074
TI  - Total antioxidant capacity of diet and risk of stroke: a population-based
      prospective cohort of women.
AB  - BACKGROUND AND PURPOSE: Consumption of antioxidant-rich foods may reduce the risk
      of stroke by inhibition of oxidative stress and inflammation. Total antioxidant
      capacity (TAC) takes into account all antioxidants and the synergistic effects
      between them. We examined the association between dietary TAC and stroke
      incidence in cardiovascular disease (CVD)-free women and in women with CVD
      history at baseline. METHODS: The study included women (31,035 CVD-free and 5680
      with CVD history at baseline), aged 49 to 83 years, from the Swedish Mammography
      Cohort. Diet was assessed with a food frequency questionnaire. Dietary TAC was
      calculated using oxygen radical absorbance capacity values. Stroke cases were
      ascertained by linkage with the Swedish Hospital Discharge Registry. RESULTS:
      During follow-up (September 1997 to December 2009), we identified 1322 stroke
      cases (988 cerebral infarctions, 226 hemorrhagic strokes, and 108 unspecified
      strokes) among CVD-free women and 1007 stroke cases (796 cerebral infarctions,
      100 hemorrhagic strokes, and 111 unspecified strokes) among women with a CVD
      history. The multivariable hazard ratio of total stroke comparing the highest
      with the lowest quintile of dietary TAC was 0.83 (95% CI, 0.70-0.99; P for
      trend=0.04) in CVD-free women. Among women with a CVD history, the hazard ratios
      for the highest versus lowest quartile of TAC were 0.90 (95% CI, 0.75-1.07; P for
      trend=0.30) for total stroke and 0.55 (95% CI, 0.32-0.95; P for trend=0.03) for
      hemorrhagic stroke. CONCLUSIONS: These findings suggest that dietary TAC is
      inversely associated with total stroke among CVD-free women and hemorrhagic
      stroke among women with CVD history.

PMID- 22135075
TI  - Letter by Nedeltchev et al regarding article, "Short-term outcomes after
      symptomatic internal carotid artery occlusion".

PMID- 22135076
TI  - Determining the modified Rankin score after stroke by postal and telephone
      questionnaires.
AB  - BACKGROUND AND PURPOSE: The modified Rankin Scale (mRS) is the most common
      outcome measure in large randomized controlled trials in stroke. We tested 2
      postal mRS questionnaires and a telephone questionnaire to determine completion
      rates and intermodality agreement. METHODS: We sent postal questionnaires
      containing 2 versions of the mRS to surviving stroke patients. One version, tick
      box, involved the patient/proxy ticking 1 of the 5 descriptions equating to mRS
      scores; the other, the simplified modified Rankin questionnaire (smRSq), included
      5 questions with yes/no responses from which the mRS is derived. We performed a
      semistructured telephone interview to consenting respondents, blinded to postal
      responses, to assign an mRS. We compared the mRS obtained by these different
      methods. RESULTS: We sent questionnaires to 343 of 356 surviving patients (96%)
      and received 225 responses (66%). The mRS could not be derived in 27 respondents
      (12%) and 10 respondents (4%) on the tick box and smRSq, respectively (difference
      in proportion, 8% [95% CI, 3-13]. One hundred three of 190 respondents (54%) to
      the postal questionnaire agreed on the tick box versus smRSq version (kappa=0.44
      [0.38, 0.50]). Agreements between the tick box versus telephone and smRSq versus
      telephone were 57% (ie, 87/152, kappa=0.47 [0.40, 0.55], and 64% (ie, 104/161,
      kappa=0.55 [0.47, 0.62], respectively. CONCLUSIONS: In large studies where face
      to-face assessment of mRS is impractical, a postal smRSq with telephone follow-up
      to nonresponders will achieve higher levels of follow-up than will the tick box
      version and also good levels of intermodality agreement with least risk of bias.

PMID- 22135077
TI  - Switching the targeting pathways of a therapeutic antibody by nanodesign.

PMID- 22135078
TI  - Successful treatment with gemtuzumab ozogamicin and donor lymphocyte infusion for
      acute myeloid leukemia relapsing after allogeneic stem cell transplantation.

PMID- 22135079
TI  - Novel ester-functionalized solid-state electrolyte for highly efficient all-solid
      state dye-sensitized solar cells.

PMID- 22135080
TI  - Comparison between two anionic reverse micelle interfaces: the role of water
      surfactant interactions in interfacial properties.
AB  - The water/sodium bis(2-ethylhexyl) phosphate (NaDEHP) reverse micelle (RM) system
      is revisited by using, for the first time, molecular probes to investigate
      interface properties. The solvatochromic behavior of 1-methyl-8-oxyquinolinium
      betaine (QB) and 6-propionyl-2-(N,N-dimethyl)aminonaphthalene (PRODAN) in the
      water/NaDEHP/toluene system is studied, and the results are compared with those
      obtained in water/sodium 1,4-bis(2-ethylhexyl) sulfosuccinate (AOT)/toluene RM
      media. The results demonstrate that the micropolarity, microviscosity,
      interfacial water structure, molecular probe partition, and intramolecular
      electron-transfer processes are dramatically altered for NaDEHP RM interfaces in
      comparison to the AOT systems. Because of organic nonpolar solvent penetration
      into the interface, NaDEHP RM media offer an interface with lower micropolarity
      and microviscosity than AOT media. Also, the interfacial water in the NaDEHP
      system shows enhanced water-water hydrogen-bond interaction in comparison with
      bulk water. The AOT RM interface represents a unique environment for PRODAN to
      undergo dual emission.

PMID- 22135081
TI  - Quantification of pluripotency transcription factor levels in embryonic stem
      cells by flow cytometry.
AB  - Embryonic stem (ES) cell lines are derived from the inner cell mass of the pre
      implantation blastocyst and are characterized by the ability to undergo
      indefinite self-renewal while retaining the potential to differentiate into each
      of the three primary germ layers. The ability of individual ES cells to self
      renew or appropriately respond to differentiation signals is influenced by the
      intracellular level of a number of crucial transcription factors. It is therefore
      important to be able to reliably quantify the levels of these proteins in single
      cells. Here we present an intracellular staining technique for flow cytometry
      suitable for monitoring transcription factor expression in ES cells. We
      illustrate the application of this technique to the detection of Oct4 and Nanog
      proteins and the coupling of this approach with fluorescent reporters of gene
      activity.

PMID- 22135082
TI  - Live-cell immunofluorescence staining of human pluripotent stem cells.
AB  - Antibodies are instrumental tools in stem cell identification, purification, and
      analysis. Most commonly, cell samples are either dissociated to obtain a single
      cell suspension suitable for FACS analysis or cell sorting, or fixed in situ for
      immunostaining and fluorescence microscopy imaging. This unit describes an
      alternative method in which live adherent cells are stained and imaged in situ
      without the need for cell dissociation, fixation, or fluorescent reporter genes.
      This minimally invasive method is particularly useful for identification and
      distinction of fully and partially reprogrammed induced pluripotent stem cells
      (iPSCs). The unit also describes the use of mCD49e and hCD29 antibodies in live
      cell (vital) imaging. mCD49e strongly stains mouse embryonic fibroblast (MEF)
      feeder cells in human pluripotent stem cell cultures, whereas hCD29 recognizes an
      antigen expressed on undifferentiated and many differentiated cells. A
      distinguishing feature of hCD29 in live-cell staining is that its antigen is
      precluded from detection wherever cells have formed tight epithelial junctions
      (e.g., in the center but not the periphery of pluripotent stem cell colonies) due
      to basolateral location. A non-fluorescent fixed-cell staining protocol is also
      provided for medium- to high-throughput quantification of stem cell experiments
      without an automated microscope. The discussion addresses technical limitations,
      pitfalls, troubleshooting, and potential applications, such as identification of
      emerging bona fide human iPSC colonies in reprogramming experiments.

PMID- 22135083
TI  - Isolation and culture of adult ciliary epithelial cells, previously identified as
      retinal stem cells, and retinal progenitor cells.
AB  - The protocols described in this unit provide detailed information on how to
      isolate and expand, in culture, ciliary epithelial cells (CECs), previously
      identified as retinal stem cells, from the adult mouse eye, and embryonic retinal
      progenitor cells (RPCs) from the developing retina. CECs are initially cultured
      in floating conditions as neurospheres and then expanded in monolayer cultures.
      RPCs are cultured in floating conditions. Detailed protocols for retinal
      differentiation, as well as exogenous gene expression using lentivirus are also
      described.

PMID- 22135084
TI  - Organotypic explant culture of glioblastoma multiforme and subsequent single-cell
      suspension.
AB  - Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM
      cell lines used in laboratory studies are frequently passaged in various culture
      media at high proliferation rates, resulting in significant genetic and molecular
      alterations. Thus, data obtained in cell lines are often inapplicable to patient
      tumors. Furthermore, recent studies suggest that there is a stem cell-like
      hierarchy among GBM cell populations and a crucial role for tumor vasculature in
      stem cells, as well as tumor growth, which cannot be reproduced in cell line
      cultures. Our laboratory has developed a novel three-dimensional (3D) organotypic
      "explant" system of surgical GBM specimens that preserves tumor cells in their
      original milieu, as well as the cytoarchitecture of the tumor stroma. Our
      previous study on the role of Notch inhibition has demonstrated a definitive
      effect on the tumor endothelium that could only be highlighted by this system. In
      this unit, we describe a detailed protocol for preparing GBM explants, and
      discuss strengths, as well as limitations of the explant system as an in vitro 3D
      model of GBM.

PMID- 22135085
TI  - VERSE-guided numerical RF pulse design: a fast method for peak RF power control.
AB  - In parallel excitation, the computational speed of numerical radiofrequency (RF)
      pulse design methods is critical when subject dependencies and system
      nonidealities need to be incorporated on-the-fly. One important concern with
      optimization-based methods is high peak RF power exceeding hardware or safety
      limits. Hence, online controllability of the peak RF power is essential. Variable
      rate selective excitation pulse reshaping is ideally suited to this problem due
      to its simplicity and low computational cost. In this work, we first improve the
      fidelity of variable-rate selective excitation implementation for discrete-time
      waveforms through waveform oversampling such that variable-rate selective
      excitation can be robustly applied to numerically designed RF pulses. Then, a
      variable-rate selective excitation-guided numerical RF pulse design is suggested
      as an online RF pulse design framework, aiming to simultaneously control peak RF
      power and compensate for off-resonance.

PMID- 22135086
TI  - High-throughput screening for various classes of doping agents using a new
      'dilute-and-shoot' liquid chromatography-tandem mass spectrometry multi-target
      approach.
AB  - A new multi-target approach based on liquid chromatography--electrospray
      ionization tandem mass spectrometry (LC-(ESI)-MS/MS) is presented to screen for
      various classes of prohibited substances using direct injection of urine
      specimens. With a highly sensitive new generation hybrid mass spectrometer
      classic groups of drugs--for example, diuretics, beta2-agonists--stimulants and
      narcotics are detectable at concentration levels far below the required limits.
      Additionally, more challenging and various new target compounds could be
      implemented. Model compounds of stimulant conjugates were studied to investigate
      a possible screening without complex sample preparation. As a main achievement,
      the integration of the plasma volume expanders dextran and hydroxyethyl starch
      (HES), commonly analyzed in time-consuming, stand-alone procedures, is
      accomplished. To screen for relatively new prohibited compounds, a common
      metabolite of the selective androgen receptor modulator (SARMs) andarine, a
      metabolite of growth hormone releasing peptide (GHRP-2), and 5-amino-4
      imidazolecarboxyamide ribonucleoside (AICAR) are analyzed. Following a completely
      new approach, conjugates of di(2-ethylhexyl) phthalate (DEHP) metabolites are
      monitored to detect abnormally high levels of plasticizers indicating for illicit
      blood transfusion. The assay was fully validated for qualitative purposes
      considering the parameters specificity, intra- (3.2-16.6%) and inter-day
      precision (0.4-19.9%) at low, medium and high concentration, robustness, limit of
      detection (1-70 ng/ml, dextran: 30 ug/ml, HES: 10 ug/ml) and ion
      suppression/enhancement effects. The analyses of post-administration and routine
      doping control samples demonstrates the applicability of the method for sports
      drug testing. This straightforward and reliable approach accomplishes the
      combination of different screening procedures resulting in a high-throughput
      method that increases the efficiency of the labs daily work.

PMID- 22135087
TI  - Absolute cerebral blood flow quantification with pulsed arterial spin labeling
      during hyperoxia corrected with the simultaneous measurement of the longitudinal
      relaxation time of arterial blood.
AB  - Quantitative arterial spin labeling (ASL) estimates of cerebral blood flow (CBF)
      during oxygen inhalation are important in several contexts, including functional
      experiments calibrated with hyperoxia and studies investigating the effect of
      hyperoxia on regional CBF. However, ASL measurements of CBF during hyperoxia are
      confounded by the reduction in the longitudinal relaxation time of arterial blood
      (T(1a) ) from paramagnetic molecular oxygen dissolved in blood plasma. The aim of
      this study is to accurately quantify the effect of arbitrary levels of hyperoxia
      on T(1a) and correct ASL measurements of CBF during hyperoxia on a per-subject
      basis. To mitigate artifacts, including the inflow of fresh spins, partial
      voluming, pulsatility, and motion, a pulsed ASL approach was implemented for in
      vivo measurements of T(1a) in the rat brain at 3 Tesla. After accounting for the
      effect of deoxyhemoglobin dilution, the relaxivity of oxygen on blood was found
      to closely match phantom measurements. The results of this study suggest that the
      measured ASL signal changes are dominated by reductions in T(1a) for brief
      hyperoxic inhalation epochs, while the physiologic effects of oxygen on the
      vasculature account for most of the measured reduction in CBF for longer
      hyperoxic exposures.

PMID- 22135088
TI  - Synthesis and characterization of 2,7-linked carbazole oligomers.
AB  - A set of monodisperse 2,7-linked carbazole oligomers (3-mer, 5-mer, 7-mer, and 9
      mer) was synthesized, and their photophysical, electrochemical, and thermal
      properties were investigated. In solutions, these oligomers exhibited bright blue
      emission with almost quantitative fluorescence quantum yield. The emission
      spectra of these oligomers in films are quite different. 3-Mer and 5-mer
      exhibited featureless emission spectra, whereas 7-mer and 9-mer showed well
      resolved emission spectra.

PMID- 22135089
TI  - Carotid atherosclerosis and chronic hepatitis C: a prospective study of risk
      associations.
AB  - There are contrasting results in studies of cardiovascular risk in patients with
      genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid
      atherosclerosis compared with a control population in order to assess the
      potential association between atherosclerosis, host and viral factors, and liver
      histological features. In all, 174 consecutive biopsy-proven G1 CHC patients were
      evaluated by anthropometric and metabolic measurements and 174 patients attending
      an outpatient cardiology unit were used as controls. Intima-media thickness (IMT)
      and carotid plaques, defined as focal thickening of >1.3 mm at the level of
      common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were
      scored by one pathologist for staging and grading, and graded for steatosis.
      Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%)
      control patients (P < 0.001). Similarly, G1 CHC patients had a greater IMT
      compared with control patients (1.04 +/- 0.21 versus 0.90 +/- 0.16; P < 0.001).
      Multivariate logistic regression analysis showed that older age (odds ratio [OR]
      1.047, 95% confidence interval [CI]: 1.014-1.082, P = 0.005), and severe hepatic
      fibrosis (OR 2.177, 95% CI: 1.043-4.542, P = 0.03), were independently linked to
      the presence of carotid plaques. In patients <=55 years, 15/67 cases with F0-F2
      fibrosis (22.3%) had carotid plaques, compared with 11/21 (52.3%) with F3-F4
      fibrosis (P = 0.008). By contrast, in patients >55 years the prevalence of
      carotid plaques was similar in those with or without severe fibrosis (25/43,
      58.1% versus 22/43, 51.1%; P = 0.51). CONCLUSION: Severe hepatic fibrosis is
      associated with a high risk of early carotid atherosclerosis in G1 CHC patients.

PMID- 22135090
TI  - Electrophysiological indices of emotion processing during retrieval of
      autobiographical memories by school-age children.
AB  - We used event-related potentials (ERPs) to examine emotion processing during
      retrieval of emotional autobiographical memories by school-age children. We
      initiated processing of the emotional experiences using neutral cue words. On one
      third of trials, children were instructed to think of a memory of a negative
      event, and on another third of trials, they were instructed to think of a memory
      of a positive event. We then recorded ERPs from 32 electrode sites as the
      children processed the emotional memories again later in the testing session. The
      7- to 10-year-old children generated memories appropriate to the valences
      specified in the instructions. Neural responses differed as a function of the
      emotional valence of the events associated with the cues and as a function of
      gender. In the sample as a whole, differential processing of positive relative to
      negative and neutral emotions was apparent at posterior electrode sites 1,000
      1,500 ms after stimulus onset. For girls, the effect was apparent beginning at
      500 ms. No differences between the neural responses to negative and neutral
      stimuli were observed. At frontal electrode sites, girls evidenced faster
      processing of positive than of negative emotion, whereas boys evidenced faster
      processing of negative than of positive emotion. In conclusion, we discuss the
      possible origins of gender-differential patterns of neural processing.

PMID- 22135091
TI  - Double-chambered left ventricle in an asymptomatic adult patient.
AB  - This article shows a case of double-chambered left ventricle in asymptomatic 60
      year-old man. This rare congenital entity is usually diagnosed in the neonatal or
      paediatric age, and it is characterized by the subdivision of the left ventricle
      in two chambers by an abnormal septum or muscle band. Differential diagnosis
      includes two other congenital left ventricular (LV) outpouching entities, such as
      diverticulum and aneurysm. As shown in our case, double-chambered left ventricle
      exhibits mixed features. A comprehensive cardiovascular magnetic imaging study is
      useful in the distinction of these closely related congenital diseases and,
      therefore, important for the correct final diagnosis.

PMID- 22135093
TI  - Multicolor labeling of living-virus particles in live cells.

PMID- 22135094
TI  - Life stages: interactions and spatial patterns.
AB  - In many stage-structured species, different life stages often occupy separate
      spatial niches in a heterogeneous environment. Life stages of the giant flour
      beetle Tribolium brevicornis (Leconte), in particular adults and pupae, occupy
      different locations in a homogeneous habitat. This unique spatial pattern does
      not occur in the well-studied stored grain pests T. castaneum (Herbst) and T.
      confusum (Duval). We propose density dependent dispersal as a causal mechanism
      for this spatial pattern. We model and explore the spatial dynamics of T.
      brevicornis with a set of four density dependent integrodifference and difference
      equations. The spatial model exhibits multiple attractors: a spatially uniform
      attractor and a patchy attractor with pupae and adults spatially separated. The
      model attractors are consistent with experimental observations.

PMID- 22135092
TI  - Functional interaction between responses to lactic acidosis and hypoxia regulates
      genomic transcriptional outputs.
AB  - Within solid tumor microenvironments, lactic acidosis, and hypoxia each have
      powerful effects on cancer pathophysiology. However, the influence that these
      processes exert on each other is unknown. Here, we report that a significant
      portion of the transcriptional response to hypoxia elicited in cancer cells is
      abolished by simultaneous exposure to lactic acidosis. In particular, lactic
      acidosis abolished stabilization of HIF-1alpha protein which occurs normally
      under hypoxic conditions. In contrast, lactic acidosis strongly synergized with
      hypoxia to activate the unfolded protein response (UPR) and an inflammatory
      response, displaying a strong similarity to ATF4-driven amino acid deprivation
      responses (AAR). In certain breast tumors and breast tumor cells examined, an
      integrative analysis of gene expression and array CGH data revealed DNA copy
      number alterations at the ATF4 locus, an important activator of the UPR/AAR
      pathway. In this setting, varying ATF4 levels influenced the survival of cells
      after exposure to hypoxia and lactic acidosis. Our findings reveal that the
      condition of lactic acidosis present in solid tumors inhibits canonical hypoxia
      responses and activates UPR and inflammation responses. Furthermore, these data
      suggest that ATF4 status may be a critical determinant of the ability of cancer
      cells to adapt to oxygen and acidity fluctuations in the tumor microenvironment,
      perhaps linking short-term transcriptional responses to long-term selection for
      copy number alterations in cancer cells.

PMID- 22135095
TI  - Searching Simkania negevensis in environmental waters.
AB  - Simkania negevensis is an obligate intracellular bacterium grouped into the order
      Chlamydiales. This new amoeba-resistant bacterium represents a novel aetiologic
      agent of bronchiolitis and community-acquired pneumonia in both adults and
      children. It has been suggested that Simkania could be an ubiquitous
      microorganism presented in water environments. In the natural history of
      infections with amoeba-related bacteria encountered in aquatic habitats, the
      transmissions by environmental aerosols or contaminated water/air systems have
      been extensively recognized. Therefore, understanding the feasibility of Simkania
      infection by these or similar routes is relevant. In the present work, we
      investigated the prevalence of this novel disease-associated microorganism in
      water samples from different sources by real-time PCR (qPCR). Our results show
      Simkania detection in 5 of 185 water analyzed samples (2.7%: 2 of 88 cooling
      towers and 3 of 8 waste water samples). However, no Simkania was detected in a
      drinking water.

PMID- 22135096
TI  - A simple method of storing nonsynnematous and synnematous isolates of Hirsutella
      thompsonii while conserving their pleomorphism, pathogenicity and genetic purity.
AB  - Five nonsynnematous and six synnematous isolates of the acaropathogenic fungus
      Hirsutella thompsonii were successfully stored as mycelial beads in sterile water
      under refrigeration. They were viable for up to 96 months without any adverse
      effect on their pleomorphic characteristics. Besides, there was loss neither in
      pathogenicity nor in genetic purity. Thus, mycelial beads can now be an addition
      to the list of fungal propagules that are amenable to storage in sterile water
      over a long period.

PMID- 22135097
TI  - The prolipoprotein diacylglyceryl transferase (Lgt) of Enterococcus faecalis
      contributes to virulence.
AB  - Enterococcus faecalis is an opportunistic pathogen responsible for nosocomial
      infections. Lipoproteins in Gram-positive bacteria are translocated across the
      plasma membrane and anchored by the fatty acid group. They perform critical
      roles, with some described as virulence determinants. The aim of this study was
      to explore the roles of E. faecalis lipoproteins in the stress response and
      virulence. We constructed a mutant affected in the predicted prolipoprotein
      diacylglyceryl transferase gene lgt, and examined the role of Lgt in membrane
      anchoring, growth, the stress response and virulence. Inactivation of lgt
      enhanced growth in a high concentration of Mn(2+) or under oxidative stress in
      vitro, and significantly decreased virulence.

PMID- 22135098
TI  - An outer membrane porin protein modulates phage susceptibility in Edwardsiella
      ictaluri.
AB  - Bacteriophages PhieiAU and PhieiDWF are lytic to the catfish pathogen
      Edwardsiella (Edw.) ictaluri. The Edw. ictaluri host factors that modulate phage
      host interactions have not been described previously. This study identified
      eleven unique Edw. ictaluri host factors essential for phage infection by
      screening a transposon mutagenized library of two Edw. ictaluri strains for phage
      resistant mutants. Two mutants were isolated with independent insertions in the
      ompLC gene that encodes a putative outer membrane porin. Phage binding and
      efficiency of plaquing assays with Edw. ictaluri EILO, its ompLC mutant and a
      complemented mutant demonstrated that OmpLC serves as a receptor for phage
      PhieiAU and PhieiDWF adsorption. Comparison of translated OmpLCs from 15 Edw.
      ictaluri strains with varying degrees of phage susceptibility revealed that amino
      acid variations were clustered on the predicted extracellular loop 8 of OmpLC.
      Deletion of loop 8 of OmpLC completely abolished phage infectivity in Edw.
      ictaluri. Site-directed mutagenesis and transfer of modified ompLC genes to
      complement the ompLC mutants demonstrated that changes in ompLC sequences affect
      the degree of phage susceptibility. Furthermore, Edw. ictaluri strain Alg-08-183
      was observed to be resistant to PhieiAU, but phage progeny could be produced if
      phage DNA was electroporated into this strain. A host-range mutant of PhieiAU,
      PhieiAU-183, was isolated that was capable of infecting strain Alg-08-183 by
      using OmpLC as a receptor for adsorption. The results of this study identified
      Edw. ictaluri host factors required for phage infection and indicated that OmpLC
      is a principal molecular determinant of phage susceptibility in this pathogen.

PMID- 22135099
TI  - Creating and modulating microdomains in pore-spanning membranes.
AB  - The architecture of the plasma membrane is not only determined by the lipid and
      protein composition, but is also influenced by its attachment to the underlying
      cytoskeleton. Herein, we show that microscopic phase separation of "raft-like"
      lipid mixtures in pore-spanning bilayers is strongly determined by the underlying
      highly ordered porous substrate. In detail, lipid membranes composed of
      DOPC/sphingomyelin/cholesterol/Gb(3) were prepared on ordered pore arrays in
      silicon with pore diameters of 0.8, 1.2 and 2 MUm, respectively, by spreading and
      fusion of giant unilamellar vesicles. The upper part of the silicon substrate was
      first coated with gold and then functionalized with a thiol-bearing cholesterol
      derivative rendering the surface hydrophobic, which is prerequisite for membrane
      formation. Confocal laser scanning fluorescence microscopy was used to
      investigate the phase behavior of the obtained pore-spanning membranes.
      Coexisting liquid-ordered- (l(o)) and liquid-disordered (l(d)) domains were
      visualized for DOPC/sphingomyelin/cholesterol/Gb(3) (40:35:20:5) membranes. The
      size of the l(o)-phase domains was strongly affected by the underlying pore size
      of the silicon substrate and could be controlled by temperature, and the
      cholesterol content in the membrane, which was modulated by the addition of
      methyl-beta-cyclodextrin. Binding of Shiga toxin B-pentamers to the Gb(3)-doped
      membranes increased the l(o)-phase considerably and even induced l(o)-phase
      domains in non-phase separated bilayers composed of
      DOPC/sphingomyelin/cholesterol/Gb(3) (65:10:20:5).

PMID- 22135100
TI  - Tuning the transition temperature and cooperativity of bapbpy-based mononuclear
      spin-crossover compounds: interplay between molecular and crystal engineering.
AB  - In this study, we show that 1) different isomers of the same mononuclear iron(II)
      complex give materials with different spin-crossover (hereafter SCO) properties,
      and 2) minor modifications of the bapbpy (bapbpy=N6,N6'-di(pyridin-2-yl)-2,2'
      bipyridine-6,6'-diamine) ligand allows SCO to be obtained near room temperature.
      We also provide a qualitative model to understand the link between the structure
      of bapbpy-based ligands and the SCO properties of their iron(II) compounds. Thus,
      seven new trans-[Fe{R(2)(bapbpy)}(NCS)(2)] compounds were prepared, in which the
      R(2)bapbpy ligand bears picoline (9-12), quin-2-oline (13), isoquin-3-oline (14),
      or isoquin-1-oline (15) substituents. From this series, three compounds (12, 14,
      and 15) have SCO properties, one of which (15) occurs at 288 K. The crystal
      structures of compounds 11, 12, and 15 show that the intermolecular interactions
      in these materials are similar to those found in the parent compound
      [Fe(bapbpy)(NCS)(2)] (1), in which each iron complex interacts with its neighbors
      through weak N-H...S hydrogen bonding and pi-pi stacking. For compounds 12 and
      15, hindering groups located near the N-H bridges weaken the N-S intermolecular
      interactions, which is correlated to non-cooperative SCO. For compound 14, the
      substitution is further away from the N-H bridges, and the SCO remains
      cooperative as in 1 with a hysteresis cycle. Optical microscopy photographs show
      the strikingly different spatio-temporal evolution of the phase transition in the
      noncooperative SCO compound 12 relative to that found in 1. Heat-capacity
      measurements were made for compounds 1, 12, 14, and 15 and fitted to the Sorai
      domain model. The number n of like-spin SCO centers per interacting domain, which
      is related to the cooperativity of the spin transition, was found high for
      compounds 1 and 14 and low for compounds 12 and 15. Finally, we found that
      although both pairs of compounds 11/12 and 14/15 are pairs of isomers their SCO
      properties are surprisingly different.

PMID- 22135102
TI  - Transmembrane dynamics of water exchange in human brain.
AB  - Tracking arterial spin labeled (ASL) water in the human brain with magnetic
      resonance imaging can provide important information on the dynamics of the trans
      capillary and trans-membrane water exchange. This information however, is not
      only important from a basic biological standpoint, but also is essential for
      deciphering positron emission tomography and MRI perfusion experiments based on
      the movement of labeled water. While substantial information exists on water
      exchange through cellular membranes in vitro, the in vivo information remains
      limited and controversial. In this MRI study, we use a combination of pulsed ASL
      and recently developed quantitative blood-oxygen-level-dependent technique to
      address this question. Our approach is based on the measurements of the intrinsic
      MR transverse relaxation (T2*) properties of the ASL-labeled water. We discovered
      that T2* of the ASL-labeled water in the extravascular space is 87 ms +/- 10 ms
      while T2* of the corresponding tissue water is much shorter, 50 ms +/- 4 ms. This
      suggests that the ASL-labeled water does not reach equilibrium with the
      extravascular tissue and is mostly localized to the extraneuronal space. We
      estimated that the water transport time through the neuronal membranes is on the
      order of several tens of seconds; a finding consistent with older PET tracer
      kinetic studies using (15)O-water.

PMID- 22135101
TI  - Effects of basic calponin on the flexural mechanics and stability of F-actin.
AB  - The cellular actin cytoskeleton plays a central role in the ability of cells to
      properly sense, propagate, and respond to external stresses and other mechanical
      stimuli. Calponin, an actin-binding protein found both in muscle and non-muscle
      cells, has been implicated in actin cytoskeletal organization and regulation. In
      this work, we studied the mechanical and structural interaction of actin with
      basic calponin, a differentiation marker in smooth muscle cells, on a single
      filament level. We imaged fluorescently labeled thermally fluctuating actin
      filaments and found that at moderate calponin binding densities, actin filaments
      were more flexible, evident as a reduction in persistence length from 8.0 to 5.8
      MUm. When calponin-decorated actin filaments were subjected to shear, we observed
      a marked reduction of filament lengths after decoration with calponin, which we
      argue was due to shear-induced filament rupture rather than depolymerization.
      This increased shear susceptibility was exacerbated with calponin concentration.
      Cryo-electron microscopy results confirmed previously published negative stain
      electron microscopy results and suggested alterations in actin involving actin
      subdomain 2. A weakening of F-actin intermolecular association is discussed as
      the underlying cause of the observed mechanical perturbations.

PMID- 22135103
TI  - Toward the Realization of a practical diketopyrrolopyrrole-based small molecule
      for improved efficiency in ternary BHJ solar cells.
AB  - An easily accessible DPP-based small molecule (DMPA-DTDPP) has been synthesized
      by a simple and efficient route. The resulting molecule, when incorporated into a
      P3HT:PCBM-based BHJ solar cell, is found to significantly improve the efficiency.
      The utility of DMPA-DTDPP as an additive yields an increase in the short circuit
      current density (Jsc) because DMPA-DTDPP serves as an energy funnel for P3HT
      excitons at the P3HT:PCBM interfaces, resulting in an improved overall power
      conversion efficiency, compared to the P3HT:PCBM control device. Considering the
      trouble-free and cost effective synthesis of DMPA-DTDPP, it may prove very useful
      in high-performance solar cells. 

PMID- 22135104
TI  - Association of thiazolidinediones with liver cancer and colorectal cancer in type
      2 diabetes mellitus.
AB  - The objective of this nationwide case-control study was to evaluate the risk of
      specific malignancy in diabetic patients who received thiazolidinediones (TZDs).
      A total of 606,583 type 2 diabetic patients, age 30 years and above, without a
      history of cancer were identified from the Taiwan National Health Insurance
      claims database during the period between January 1 2000 and December 31 2000. As
      of December 31 2007, patients with incident cancer of liver, colorectal, lung,
      and urinary bladder were included as cases and up to four age- and sex-matched
      controls were selected by risk-set sampling. Logistic regression models were
      applied to estimate the odds ratio (OR) and 95% confidence interval (CI) between
      TZDs and cancer incidence. A total of 10,741 liver cancer cases, 7,200 colorectal
      cancer cases, and 70,559 diabetic controls were included. A significantly lower
      risk of liver cancer incidence was found for any use of rosiglitazone (OR: 0.73,
      95% CI: 0.65-0.81) or pioglitazone (OR: 0.83, 95% CI: 0.72-0.95), respectively.
      The protective effects were stronger for higher cumulative dosage and longer
      duration. For colorectal cancer, rosiglitazone, but not pioglitazone, was
      associated with a significantly reduced risk (OR: 0.86; 95% CI: 0.76-0.96). TZDs
      were not associated with lung and bladder cancer incidence, although a potential
      increased risk for bladder cancer with pioglitazone use >=3 years could not be
      excluded (OR: 1.56; 95% CI: 0.51-4.74). CONCLUSION: The use of pioglitazone and
      rosiglitazone is associated with a decreased liver cancer incidence in diabetic
      patients. The effects on occurrence of specific cancer types may be different for
      pioglitazone and rosiglitazone.

PMID- 22135106
TI  - Sizing up information distortion: quantifying its effect on the subjective values
      of choice options.
AB  - When choosing between options, people often distort new information in a
      direction that favors their developing preference. Such information distortion is
      widespread and robust, but less is known about the magnitude of its effects. In
      particular, research has not quantified the effects of distortion relative to the
      values of the choice options. In two experiments, we manipulated participants'
      initial preferences in choices between risky three-outcome monetary gambles (win,
      lose, or neither) by varying the order of five information items (e.g., amount to
      win, chance of losing). In Experiment 1 (N = 397), the effect of initial
      information on gambles' certainty equivalents (subjective values) was mediated by
      the distortion of later information. The indirect effect on the difference
      between gambles' certainty equivalents averaged 27% of the gambles' mean expected
      value. In Experiment 2 (N = 791), we increased the difference between gambles on
      a later information item to overcome the effect of initial information on
      participants' choices. The required change averaged 31% of the gambles' mean
      expected value. We conclude that the effects of information distortion can be
      substantial.

PMID- 22135105
TI  - Catalytic enantioselective 1,2-diboration of 1,3-dienes: versatile reagents for
      stereoselective allylation.
AB  - More with boron: The development of catalytic enantioselective 1,2-diboration of
      1,3-dienes enables a new strategy for enantioselective carbonyl allylation
      reactions (see scheme). These reactions occur with outstanding levels of
      stereoselection and can be applied to both monosubstituted and 1,1-disubstituted
      dienes. The carbonyl allylation reactions provide enantiomerically enriched
      functionalized homoallylic alcohol products.

PMID- 22135107
TI  - Learning new vocabulary in German: the effects of inferring word meanings, type
      of feedback, and time of test.
AB  - In the present study, introductory-level German students read a simplified story
      and learned the meanings of new German words by reading English translations in
      marginal glosses versus trying to infer (i.e., guess) their translations.
      Students who inferred translations were given feedback in English or in German,
      or no feedback at all. Although immediate retention of new vocabulary was better
      for students who used marginal glosses, students who inferred word meanings and
      then received English feedback forgot fewer translations over time. Plausible but
      inaccurate inferences (i.e., those that made sense in the context) were more
      likely to be corrected by students who received English feedback as compared with
      German feedback, providing support for the beneficial effects of mediating
      information. Implausible inaccurate inferences, however, were more likely to be
      corrected on the delayed vocabulary test by students who received German feedback
      as compared with English feedback, possibly because of the additional contextual
      support provided by German feedback.

PMID- 22135108
TI  - Optimization studies on gastroretentive floating system using response surface
      methodology.
AB  - The aim of the present investigation was to develop and optimize gastroretentive
      floating system of amoxicillin for the efficient treatment of peptic ulcer
      induced by Helicobacter pylori infection. Floating microballoons were developed
      using central composite design (CCD), and optimization was done by employing
      response surface methodology. The selected independent variables were cellulose
      acetate phthalate, drug-Eudragit S100 ratio, and the ratio of
      dichloromethane/ethanol/isopropyl alcohol. The selected dependent variables were
      yield, mean particle size, buoyancy, encapsulation efficiency, and drug release
      within 8 h. A quadratic polynomial model was generated which had linear,
      interaction, and quadratic terms to predict and evaluate the independent
      variables with respect to the dependent variables. Results showed that selected
      independent variables significantly affect the yield (30.53-82.71%), particle
      size (31.62-47.03 MUm), buoyancy (42.68-95.75%), encapsulation efficiency (56.96
      93.13%), and cumulative drug release from the microballoons (34.01-74.65%). The
      interaction and quadratic terms were also found to affect the process variables.
      An excellent agreement was found between the actual value and predicted value. In
      conclusion, it can be said that CCD is a valuable second-degree design to develop
      and optimize GFS of amoxicillin which in turn provides a basis to localize the
      drug release in the gastric region for effective treatment of H. pylori-mediated
      infection.

PMID- 22135109
TI  - Carbonyl-functionalized quaterthiophenes: a study of the vibrational Raman and
      electronic absorption/emission properties guided by theoretical calculations.
AB  - This work investigates the evolution of the molecular, vibrational, and optical
      properties within a family of carbonyl-functionalized quaterthiophenes: 5,5'''
      diheptanoyl-2,2':5',2'':5'',2'''-quaterthiophene (1), 5,5'''
      diperfluorohexylcarbonyl-2,2':5',2'':5'',2'''-quaterthiophene (2), and 2,7-[bis(5
      perfluorohexylcarbonylthien-2-yl)]-4H-cyclopenta[2,1-b:3,4-b']-dithiophene-4-one
      (3). The analysis is performed by Raman and UV/Vis
      absorption/excitation/fluorescence spectroscopy in combination with density
      functional calculations. Theoretical calculations show that substitution with
      carbonyl groups and perfluorohexyl chains induces progressive quinoidization of
      the pi-conjugated backbone in comparison to the carbonyl-free compound 5,5'''
      dimethyl-2,2':5',2'':5'',2'''-quaterthiophene (DM-4T) used as reference. Raman
      spectra are dominated by a strong Raman line which mainly corresponds to a
      combination of C-C/C=C stretching vibrations spreading over the whole thiophene
      core. This band undergoes a remarkable downshift as a consequence of the
      structural changes induced by the electron-withdrawing groups on the pi
      conjugated backbone. The band splitting on incorporation of a central carbonyl
      bridge evidences the formation of two structural domains in the molecule. The
      excitation and fluorescence spectra recorded at low temperature show well
      resolved vibronic structures associated with the most intense collective C-C/C=C
      stretching mode. Optical absorption and fluorescence bands exhibit remarkable
      bathochromic dispersion on carbonyl functionalization, indicative of extension of
      pi conjugation. TDDFT calculations enable a detailed description of the trends
      observed in the absorption spectra. Resonance Raman spectra reflect the
      structural changes predicted for the S(0)->S(1) electronic transition and
      evidence the cross-conjugated character that the central carbonyl group confers
      on 3.

PMID- 22135110
TI  - Is the conventional interpretation of the anisotropic effects of C=C double bonds
      and aromatic rings in NMR spectra in terms of the pi-electron
      shielding/deshielding contributions correct?
AB  - Based on the nucleus-independent chemical shift (NICS) concept, isotropic
      magnetic shielding values have been computed along the three Cartesian axes for
      ethene, cyclobutadiene, benzene, naphthalene, and benzocyclobutadiene, starting
      from the molecular/ring center up to 10 A away. These through-space NMR
      spectroscopic shielding (TSNMRS) values, which reflect the anisotropic effects,
      have been broken down into contributions from localized- and canonical molecular
      orbitals (LMOs and CMOs); these contributions revealed that the proton NMR
      spectroscopic chemical shifts of nuclei that are spatially close to the C=C
      double bond or the aromatic ring should not be explained in terms of the
      conventionally accepted pi-electron shielding/deshielding effects. In fact, these
      effects followed the predictions only for the antiaromatic cyclobutadiene ring.

PMID- 22135111
TI  - Hepatic arterial infusion chemotherapy with a coaxial reservoir system using a
      non-braided spiral tip microcatheter.
AB  - PURPOSE: To evaluate the efficacy and safety of a coaxial reservoir system with a
      non-braided spiral tip microcatheter and exclusive port for hepatic arterial
      infusion chemotherapy. MATERIALS AND METHODS: In vitro evaluation included
      evaluation of pressure tolerance/flow rate of the coaxial reservoir system, and
      the strength of connection between the 2.7-F catheter and port. Due to the
      difficulty of implanting conventional reservoirs, coaxial reservoirs were
      implanted via the femoral artery of 80 patients. We implanted a non-braided 2.7-F
      microcatheter with a spiral shaped tip, 5-F catheter, and a port. Clinical
      assessment included evaluation of technical success and complications. RESULTS:
      In vitro evaluation of the coaxial reservoir at its maximum pressure load showed
      that flow rates for 300 mg I/mL iopamidol contrast medium were 0.25 +/- 0.04 mL/s
      (undiluted), 1.03 +/- 0.01 mL/s (50% dilution), and 2.91 +/- 0.01 mL/s (30%
      dilution). Connection strength between the 2.7-F catheter and port was 13.4 +/-
      0.57 N. Percutaneous port catheter placement was successful in all patients
      (100%, n = 80). Complications included hepatic arterial occlusion (10%, n = 8),
      catheter tip dislocation (1.3%, n = 1), and catheter occlusion (1.3%, n = 1).
      CONCLUSIONS: A coaxial reservoir system with a non-braided microcatheter and
      exclusive port is safe and effective for difficulty of implanting conventional
      reservoir.

PMID- 22135112
TI  - Precision of the measurement of CT numbers: comparison of dual-energy CT spectral
      imaging with fast kVp switching and conventional CT with phantoms.
AB  - PURPOSE: To compare dual-energy computed tomography (CT) spectral imaging and
      conventional CT imaging in terms of precision of the measurement of CT numbers in
      phantoms. MATERIALS AND METHODS: A circular phantom (CP) and an elliptical
      phantom (EP) were used. Capsules filled with iodine contrast media solutions at
      various concentration levels were placed in the phantoms. Conventional CT was
      performed at a tube voltage of 120 kVp. Simulated monochromatic images at 65 keV
      were obtained by dual-energy CT spectral imaging. The CT number of each iodine
      capsule was measured. A linear regression model was used to evaluate linearity,
      while analysis of covariance was used to investigate the degree of variability
      according to phantom shape for each imaging method. RESULTS: With conventional
      imaging, the slopes of the regression lines for CT numbers measured at the EP
      center and EP periphery were significantly lower than those measured for CP (P <
      0.0001 for both EP center vs. CP and for EP periphery vs. CP). No significant
      difference in slope was found among phantom shapes in dual-energy spectral CT
      imaging. CONCLUSION: Computed tomography numbers varied considerably depending on
      the phantom shape in conventional CT, whereas dual-energy CT provided consistent
      CT numbers regardless of the phantom shape.

PMID- 22135113
TI  - Usefulness of portography and contrast-enhanced computed tomography to predict
      the embolized area in percutaneous transhepatic portal vein embolization with
      absolute ethanol under temporary balloon occlusion.
AB  - PURPOSE: To assess the usefulness of portography and contrast-enhanced computed
      tomography (CECT) for predicting the embolized area after the first injection of
      absolute ethanol (AE) in right portal vein embolization (RPVE). MATERIALS AND
      METHODS: Portograms were retrospectively reviewed in 50 patients (30 men and 20
      women, mean age 65 years) who had undergone percutaneous transhepatic RPVE with
      AE under temporary balloon occlusion (TBO) between February 2002 and October
      2009. The enhancement pattern before embolization and the embolization pattern
      after the first AE injection were analyzed by portography. The angles of portal
      branches against the horizontal plane were measured in 48 patients using pre
      treatment CECT. RESULTS: The enhancement pattern was not consistent with the
      embolization pattern in 35 patients (p < 0.001). When the anterior branch angles
      were divided into two groups at -5 degrees , 0 degrees , 10 degrees , and 15
      degrees , the frequency of the posterior-branch-dominant embolization pattern was
      higher in the more negatively angled group (p = 0.002-0.041). CONCLUSION: The
      distribution of AE is different from that of contrast medium in percutaneous
      transhepatic RPVE under TBO. The pre-treatment measurement of the angles of
      portal branches against the horizontal plane on CECT is suggested to be useful
      for predicting the embolized area.

PMID- 22135114
TI  - Long-term assessment of contrast effects of gadofluorine M and gadofluorine P in
      magnetic resonance imaging of mice.
AB  - PURPOSE: To investigate the long-term time course of the contrast effects after
      the intravenous injection of gadofluorine M or gadofluorine P in mice. MATERIALS
      AND METHODS: Magnetic resonance images were acquired longitudinally after
      intravenous injection of 0.1 MUmol Gd/g gadofluorine M into BALB/c mice. The
      contrast effects were also assessed in C57BL/6J mice injected with gadofluorine
      M, BALB/c mice injected with gadofluorine P, and BALB/c mice injected with a
      double dose of gadopentetate dimeglumine. RESULTS: The injection of gadofluorine
      M into BALB/c mice caused prolonged contrast effects in the blood and other
      organs. The liver enhancement was especially long-lasting and still evident 6
      days after injection. Strain-related differences in contrast kinetics of
      gadofluorine M were not observed between BALB/c mice and C57BL/6J mice. In
      comparison with gadofluorine M, clearances from the blood, liver, and kidney were
      more rapid and contrast enhancement in the spleen was generally lower for
      gadofluorine P. The enhancement in the gallbladder cavity, indicating biliary
      excretion, was evident only after gadofluorine P injection. Blood enhancement at
      10 min was much weaker for gadopentetate dimeglumine. CONCLUSION: Both
      gadofluorine M and gadofluorine P appear to be applicable to blood pool imaging
      and liver imaging in mice.

PMID- 22135115
TI  - Optically active helical substituted polyacetylenes showing reversible helix
      inversion in emulsion and solution state.
AB  - This Communication reports two substituted polyacetylenes that can adopt helical
      structures of preferential screw sense in both emulsion (nanoparticle) and
      solution; however, the handedness of the macromolecular helices is just opposite
      in the two states. More interestingly, the helical screw sense of the polymers
      demonstrated a reversible transition between the two states. The unprecedented
      findings are of significant importance for acquiring new insights into helical
      polymers and for developing novel advanced chiral materials.

PMID- 22135116
TI  - Economic model of a birth cohort screening program for hepatitis C virus.
AB  - Recent research has identified high hepatitis C virus (HCV) prevalence among
      older U.S. residents who contracted HCV decades ago and may no longer be
      recognized as high risk. We assessed the cost-effectiveness of screening 100% of
      U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared
      with current risk-based screening, by projecting costs and outcomes of screening
      over the remaining lifetime of this birth cohort. A Markov model of the natural
      history of HCV was developed using data synthesized from surveillance data,
      published literature, expert opinion, and other secondary sources. We assumed
      eligible patients were treated with pegylated interferon plus ribavirin, with
      genotype 1 patients receiving a direct-acting antiviral in combination. The
      target population is U.S. residents born 1946-1970 with no previous HCV
      diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected)
      eligible for screening, birth-cohort screening leads to 84,000 fewer cases of
      decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000
      fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort
      screening leads to higher overall costs than risk-based screening ($80.4 billion
      versus $53.7 billion), but yields lower costs related to advanced liver disease
      ($31.2 billion versus $39.8 billion); birth-cohort screening produces an
      incremental cost-effectiveness ratio (ICER) of $37,700 per quality-adjusted life
      year gained versus risk-based screening. Sensitivity analyses showed that
      reducing the time horizon during which health and economic consequences are
      evaluated increases the ICER; similarly, decreasing the treatment rates and
      efficacy increases the ICER. Model results were relatively insensitive to other
      inputs. CONCLUSION: Birth-cohort screening for HCV is likely to provide important
      health benefits by reducing lifetime cases of advanced liver disease and HCV
      related deaths and is cost-effective at conventional willingness-to-pay
      thresholds.

PMID- 22135117
TI  - Assessing asset indices.
AB  - The use of asset indices in welfare analysis and poverty targeting is increasing,
      especially in cases in which data on expenditures are unavailable or hard to
      collect. We compare alternative approaches to welfare measurement. Our analysis
      shows that inferences about inequalities in education, health care use,
      fertility, and child mortality, as well as labor market outcomes, are quite
      robust to the economic status measure used. Different measures-most significantly
      per capita expenditures versus the class of asset indices-do not, however, yield
      identical household rankings. Two factors stand out in predicting the degree of
      congruence in rankings. First is the extent to which expenditures can be
      explained by observed household and community characteristics. Rankings are most
      similar in settings with small transitory shocks to expenditure or with little
      random measurement error in expenditure. Second is the extent to which
      expenditures are dominated by individually consumed goods, such as food. Asset
      indices are typically derived from indicators of goods that are effectively
      public at the household level, while expenditures are often dominated by food, an
      almost exclusively private good. In settings in which individually consumed goods
      are the main component of expenditures, asset indices and per capita consumption
      yield the least similar results.

PMID- 22135118
TI  - A general strategy to construct fluorogenic probes from charge-generation
      polymers (CGPs) and AIE-active fluorogens through triggered complexation.
AB  - Trip the light of plastic: An aqueous fluorogenic sensing system consisting of
      selective and specific analyte-triggerable charge-generation polymers (CGPs) and
      a negatively charged aggregation-induced emission active fluorogen (TPE-COOH(4))
      is presented. In the presence of a triggering analyte of interest, the CGPs
      undergo electrostatic complexation with TPE-COOH(4) leading to intense
      fluorescence emission due to the aggregation of TPE-COOH(4).

PMID- 22135119
TI  - Risk stratification in acute coronary syndromes.
AB  - Accurate and readily available systems for risk stratification and a wide array
      of antithrombotic agents, on top of classical anti-ischemic drugs, provide the
      noninvasive cardiologist admitting the patient in the CCU with an effective and
      reliable armamentarium for the safe management of most patients with ACS. From
      the interventionalist's perspective, the immediate knowledge of the coronary
      anatomy yields the most valuable information to address the most appropriate
      treatment. The sooner angiography is performed the higher the benefit for
      patients at moderate to high risk, but if performed by expert teams and with the
      correct use of modern drugs and devices, the invasive approach has the potential
      to reduce costs and length of hospital stay also in low-risk patients. Although
      still some reluctance remains to equalize treatment strategies for patients with
      STEMI to those with NSTEMI, such differences will likely disappear in the near
      future with upcoming new evidence. Cardiac surgery may represent a life-saving
      alternative for patients presenting with NSTEMI evolving in cardiogenic shock or
      with mechanical complications, or in patients unsuitable for PCI or with failed
      PCI attempts. In stabilized conditions after the treatment of the culprit lesion,
      patients with severe multivessel disease may benefit from cardiac surgery to
      complete myocardial revascularization. Indications for CABG in this setting
      should be evaluated in the context of a local "heart team" or through
      prespecified protocols in centers without cardiac surgery on site.

PMID- 22135120
TI  - Prevalence of skin lesions in familial adenomatous polyposis: a marker for
      presymptomatic diagnosis?
AB  - BACKGROUND AND AIMS: Benign skin tumors such as lipomas, fibromas, and epidermal
      cysts are among the extracolonic manifestations of familial adenomatous polyposis
      (FAP). Readily detectable by inspection, they could serve as presymptomatic
      diagnostic markers to identify FAP patients. We therefore prospectively
      determined the prevalence of cutaneous lesions in genetically confirmed
      adenomatous polyposis coli (APC) mutation carriers and assessed their potential
      usefulness in the identification of FAP patients. METHODS: Whole-skin examination
      was performed in 56 adult APC mutation carriers, compared with a control group (n
      = 116). In addition, FAP patients were investigated for the presence of
      congenital hypertrophy of the retinal pigment epithelium (CHRPE), an established
      clinical marker for FAP, and a detailed review of medical records was performed.
      RESULTS: Nearly half of all FAP patients (48.2%) had at least one FAP-associated
      skin lesion, compared with one third (34.5%) of controls. Only multiple lipomas
      and combined skin lesions were significantly more prevalent in APC mutation
      carriers. CHRPE was observed in 22 (43.1%) of 51 FAP patients, including 14
      (37.8%) of 37 individuals with APC mutations outside the CHRPE-associated region
      between codons 311 and 1465. CONCLUSIONS: Despite a significantly higher
      prevalence of multiple lipomas, occurring at younger age, and combined skin
      lesions in APC mutation carriers, the low diagnostic sensitivity of FAP
      associated skin lesions precludes their use as markers for FAP in clinical
      practice. Based on our findings, the common CHRPE-associated region should be
      extended to APC codons 148-2043.

PMID- 22135121
TI  - The outcomes and safety of single-agent sorafenib in the treatment of elderly
      patients with advanced hepatocellular carcinoma (HCC).
AB  - BACKGROUND: With the aging population, hepatocellular carcinoma (HCC) in the
      elderly represents a significant health burden. We aimed to evaluate and compare
      the efficacy and tolerability of single-agent sorafenib in treating elderly
      patients with advanced HCC versus the younger population. METHODS: We
      retrospectively analyzed a consecutive cohort of advanced HCC patients with Child
      Pugh A or B liver function and an Eastern Cooperative Oncology Group performance
      status score of 0-2 treated with sorafenib. The patients were categorized into
      older (age >=70 years) and younger (age <70 years) groups. Treatment outcomes and
      related adverse events (AEs) were compared. RESULTS: In total, 172 patients, 35
      in the older (median age, 73 years) and 137 in the younger (median age, 55 years)
      group, were analyzed. The median progression-free survival time was similar in
      the older and younger groups (2.99 months versus 3.09 months; p = .275), as was
      the overall survival time (5.32 months versus 5.16 months; p = .310). Grade 3 or
      4 AEs were observed in 68.6% of older and 62.7% of younger patients (p = .560),
      with neutropenia (11.4% versus 0.7%; p = .007), malaise (11.4% versus 2.2%; p =
      .033), and mucositis (5.7% versus 0.0%; p = .041) being more frequently reported
      in the elderly cohort. CONCLUSIONS: The survival benefits and overall treatment
      related AEs of sorafenib are comparable in elderly and younger advanced HCC
      patients. Nevertheless, more vigilant monitoring in the elderly is warranted
      because they are more susceptible to develop neutropenia, malaise, and mucositis.

PMID- 22135122
TI  - The effect of cigarette smoking on cancer treatment-related side effects.
AB  - BACKGROUND: Cigarette smoking has long been implicated in cancer development and
      survival. However, few studies have investigated the impact of smoking on symptom
      burden in cancer survivors during treatment and at survivorship stage. This study
      examines the influence of cigarette smoking on side effects among 947 cancer
      patients during and 6 months following treatment. METHODS: Patients diagnosed
      with cancer and scheduled to receive chemotherapy and/or radiation therapy
      reported on current smoking status (yes, no) and total symptom burden [the sum of
      12 common symptoms (fatigue, hair loss, memory, nausea, depression, sleep, pain,
      concentration, hot flashes, weight loss, skin problems, and dyspnea) scored on an
      11-point scale ranging from 0 = "not present" to 10 = "as bad as you can
      imagine"] during treatment and at 6-month follow-up. The adjusted mean total
      symptom burden by smoking status was determined by analysis of covariance
      controlling for age, gender, race, education, occupation, treatment, cancer site,
      and Karnofsky performance score. RESULTS: During treatment, smokers (S) had a
      significantly higher total symptom burden than nonsmokers (NS) (S = 46.3 vs. NS =
      41.2; p < 0.05). At 6-month follow-up, smokers continued to report a higher total
      symptom burden than nonsmokers (S = 27.7 vs. NS = 21.9; p < 0.05). Participants
      who quit smoking before treatment levels had a total symptom burden similar to
      nonsmokers. CONCLUSION: Smoking was associated with an increased symptom burden
      during and following treatments for cancer. Targeted cessation efforts for
      smokers to decrease symptom burden may limit the likelihood of treatment
      interruptions and increase quality of life following treatment.

PMID- 22135124
TI  - Construction of metal-organic frameworks: versatile behaviour of a ligand
      containing mono- and bidentate coordination sites.
AB  - Five new coordination polymers based on a new 2,2'-bipyridine derived ligand N,N'
      bis(pyridin-4-yl)-2,2'-bipyridine-5,5'-dicarboxamide (=L) are reported herein.
      Isostructural three-dimensional coordination polymers with a rare (4,6)-connected
      network of {4(4).6(2)}(3){4(6).8(9)}(2) topology were synthesised from
      Cu(NO(3))(2), Zn(NO(3))(2) or a mixture of Cu(NO(3))(2)/Fe(BF(4))(2) with L in
      complexes {[Cu(5)L(6)].(NO(3))(10).(H(2)O)(18)}(infinity) (1),
      {[Zn(5)L(6)].(NO(3))(10).(H(2)O)(18)}(infinity) (2) and
      {[Fe(x)Cu(y)L(6)].(NO(3))(10).(H(2)O)(18)}(infinity) (3; where x+y=5). Complexes
      with two-dimensional grid structures resulted from treatment with CoCl(2) or
      Cd(NO(3))(2) with L in complexes {[CoLCl(2)].DMF}(infinity) (4) and
      {CdL(NO(3))(2)}(infinity) (5).

PMID- 22135123
TI  - Toxicity as a biomarker of efficacy of molecular targeted therapies: focus on
      EGFR and VEGF inhibiting anticancer drugs.
AB  - In addition to being present in tumor cells, many targets of signal transduction
      inhibitors are also found in normal tissue. Side effects attributable to the
      mechanism of action of molecular targeted agents thus represent "on-target"
      modulation in normal tissues. These mechanism-based toxicities can be
      pharmacodynamic effects of pathway inhibition and, in tumors depending on the
      inhibited pathway for proliferation, might be biomarkers of efficacy. The
      development of rash with tyrosine kinase inhibitors or monoclonal antibodies
      targeting the epidermal growth factor receptor is associated with superior
      outcomes in lung, head and neck, colorectal, and pancreatic cancer studies.
      Correlated with superior efficacy in retrospective analyses of large studies in
      advanced colorectal, breast, and renal cell carcinoma, arterial hypertension as
      an adverse event of antiangiogenic agents may also be a marker of effective
      target inhibition. An association between hypothyroidism and the activity of
      multitargeted tyrosine kinase inhibitors has been identified in renal cell
      carcinoma patients. Tumor growth addiction to the specific pathway that is
      effectively targeted may be the link between a mechanism-based toxicity and
      efficacy. The biological basis for this correlation can be pharmacological, with
      higher drug exposure being associated with greater toxicity and antitumor
      activity, and can also be genetic, because single nucleotide polymorphisms play
      an important role in drug pharmacokinetic and pharmacodynamic processes.
      Investigators have proposed that interpatient differences and associated
      toxicities can be exploited for dose selection and titration, and clinical trials
      are currently exploring intrapatient "dosing-to-toxicity" strategies. Ultimately,
      the predictive value of a side effect of molecular targeted therapies requires
      validation in prospective trials.

PMID- 22135126
TI  - Pancreatic adenocarcinoma: complete tumor extirpation improves survival benefit
      despite larger tumors for patients who undergo distal pancreatectomy and
      splenectomy.
AB  - INTRODUCTION: Patients with pancreatic adenocarcinoma have poor survival.
      Presumably, tumors in the body or tail of the pancreas, due to paucity of
      symptoms, present later than patients with tumors in the head of the pancreas.
      This study was undertaken to determine if tumors amenable to complete extirpation
      by distal pancreatectomy/splenectomy have worse survival when compared to their
      proximal counterparts. METHODS: Since 1992, patients undergoing
      pancreaticoduodenectomy or distal pancreatectomy/splenectomy for pancreatic
      adenocarcinoma have been prospectively followed. The impact of resection was
      evaluated using a survival curve analysis (Mantel-Cox). Data are presented as
      median, mean +/- SD. RESULTS: Two hundred twenty patients underwent
      pancreaticoduodenectomy and 33 patients underwent distal
      pancreatectomy/splenectomy for pancreatic adenocarcinoma. Comparing overall
      survival, there was not a significant difference between patients undergoing
      pancreaticoduodenectomy (16.8 months, 25.6 +/- 26) and distal
      pancreatectomy/splenectomy (15.2 months, 19.7 +/- 18.6), p = 0.34. Patients
      undergoing distal pancreatectomy/splenectomy had significantly larger tumors (4
      cm, 5 +/- 2.3) compared to patients undergoing pancreaticoduodenectomy (3 cm, 3
      +/- 1.4), p = 0.005. CONCLUSION: Long-term survival after resection of pancreatic
      adenocarcinoma is poor despite the location within the pancreas. Complete tumor
      extirpation continues to be an independent predictor of survival, regardless of
      operation undertaken, despite larger tumors for patients who undergo distal
      pancreatectomy/splenectomy.

PMID- 22135125
TI  - Knee confidence as it relates to physical function outcome in persons with or at
      high risk of knee osteoarthritis in the osteoarthritis initiative.
AB  - OBJECTIVE: To evaluate whether low knee confidence at baseline is associated with
      poor baseline-to-3-year physical function outcome in the Osteoarthritis
      Initiative. METHODS: Knee confidence was assessed using an item from the Knee
      Injury and Osteoarthritis Outcome Score instrument. Physical function was
      assessed using self-report measures (Western Ontario and McMaster Universities
      Osteoarthritis Index [WOMAC] function score and Short Form 12 physical component
      scale) and performance-based measures (20-meter walk and chair stand test). Poor
      function outcome was defined as moving into a worse function group or remaining
      in the 2 worst function groups between baseline and 3 years. Logistic regression
      was used to evaluate the relationship between baseline knee confidence level and
      poor baseline-to-3-year function outcome, adjusting for potential confounders.
      RESULTS: The sample included 3,975 men and women with or at high risk of
      developing osteoarthritis of the knee, of whom 37-53% had poor baseline-to-3-year
      function outcome. For both self-report measures, increasingly worse knee
      confidence was associated with a greater risk of poor function outcome, and trend
      tests supported a graded response (e.g., the adjusted odds ratios [95% confidence
      intervals] for the WOMAC function score for worsening confidence categories were
      1.26 [1.07-1.49], 1.43 [1.16-1.77], and 2.05 [1.49-2.82], P for trend <0.0001).
      Similar associations between confidence and performance-based function outcome
      were observed, but statistical significance did not persist in adjusted analyses.
      Factors independently associated with poor function outcome for all 4 outcome
      measures were depressive symptoms, comorbidity, body mass index, and joint space
      narrowing. CONCLUSION: These findings indicate that worse knee confidence at
      baseline is independently associated with greater risk of poor function outcome
      by self-report measures, with evidence of a graded response; the relationship
      with performance measures is not significant in fully adjusted models.

PMID- 22135127
TI  - Diagnostic accuracy of 4D-CT for parathyroid adenomas and hyperplasia.
AB  - BACKGROUND AND PURPOSE: 4D-CT is a novel method of multiphase CT imaging. When
      used to localize parathyroid adenomas and hyperplasia, this technique may allow
      for more robust diagnostic accuracy than traditional sonography and nuclear
      scintigraphy techniques. The purpose of our study is to assess the accuracy of 4D
      CT for localizing pathologically proved parathyroid adenomas and hyperplasia
      found during surgery. MATERIALS AND METHODS: A total of 35 pathologically proved
      cases of parathyroid adenoma and hyperplasia were retrospectively reviewed
      between January 2009 and March 2011. Inclusion criteria were availability of
      final surgical pathology and performance of preoperative 4D-CT. No cases were
      excluded. Sensitivity, specificity, and accuracy of 4D-CT were ascertained
      including both the side and quadrant of the pathologically proved lesion.
      RESULTS: Of the 35 pathologically proved cases collected over the study period,
      32 (sensitivity = 91%) patients were found positive for parathyroid disease using
      4D-CT, including 3 cases of multigland disease. For lateralization of single
      gland disease, 4D-CT demonstrated an accuracy of 93%. 4D-CT revealed a suboptimal
      44% sensitivity, but 100% specificity, for multigland disease. CONCLUSIONS: 4D-CT
      demonstrated a high diagnostic accuracy for single and multigland disease in our
      cohort. Importantly, 4D-CT accurately lateralized single-gland adenomas in >90%
      of cases, allowing the surgeon to employ a directed operative approach. 4D-CT
      also showed a very high specificity for the detection of multigland disease.

PMID- 22135128
TI  - Systematic review of methods for assessing leptomeningeal collateral flow.
AB  - BACKGROUND AND PURPOSE: The importance of LMF in the outcome after acute ischemic
      stroke is increasingly recognized, but imaging presents a wide range of options
      for identification of collaterals and there is no single system for grading
      collateral flow. The aim of this study was to systematically review the
      literature on the available methods for measuring LMF adequacy. MATERIALS AND
      METHODS: We performed a systematic review of Ovid, MEDLINE, and Embase databases
      for studies in which flow in the leptomeningeal collateral vessels was evaluated.
      Imaging technique, grading scale, and reliability assessment for collateral flow
      measurement were recorded. RESULTS: We found 81 publications describing 63
      methods for grading collateral flow on the basis of conventional angiography (n =
      41), CT (n = 7), MR imaging (n = 9), and transcranial Doppler (n = 6). Inter-
      and/or intraobserver agreement was assessed in only 8 publications. CONCLUSIONS:
      There is inconsistency in how LMF is graded, with a variety of grading scales and
      imaging modalities being used. Consistency in evaluating collateral flow at
      baseline is required for the impact of collateral flow to be fully appreciated.

PMID- 22135129
TI  - Clopidogrel (plavix).
AB  - Clopidogrel is an inhibitor of platelet aggregation, indicated for the prevention
      of ischemic stroke and in-stent thrombosis. However, it has a number of
      drawbacks, including an increased risk of hemorrhage; a clinical effect that is
      slow in onset and irreversible; a genetically determined variability in its
      clinical potency; and interactions with other commonly administered drugs.

PMID- 22135130
TI  - Imaging approaches for dementia.
AB  - Brain imaging has progressed from exclusion of rare treatable mass lesions to a
      specific antemortem diagnosis. MR imaging-derived hippocampal atrophy and WMH are
      regarded as imaging biomarkers of AD and CVD respectively. Abnormal FP-CIT SPECT
      or cardiac iodobenzamide SPECT is a useful supportive imaging feature in the
      diagnosis of DLB. Frontal and/or anterior temporal atrophy and anterior defects
      on molecular imaging with FDG-PET or perfusion SPECT are characteristic of FTDs.
      Whole-body FDG-PET may be helpful in patients with rapidly progressing
      "autoimmune dementias," and FLAIR and DWI are indicated in suspected CJD. A major
      role of imaging is in the development of new drugs and less costly biomarkers.

PMID- 22135131
TI  - Immediate and midterm results following treatment of recently ruptured
      intracranial aneurysms with the Pipeline embolization device.
AB  - BACKGROUND AND PURPOSE: A number of flow-diverting devices have become available
      for endovascular occlusion of cerebral aneurysms. This article reports immediate
      and midterm results in recently ruptured aneurysms treated with the PED.
      MATERIALS AND METHODS: A prospective registry was established at 3 Australian
      neurointerventional sites to collect data on ruptured and unruptured aneurysms
      treated with PED during a 12-month period from August 2009. From this data base
      of 65 patients, 11 cases of recent aneurysmal SAH were examined. Relevant data
      including antiplatelet therapy, technical issues, complications, and imaging
      findings during at least a 6-month period of follow-up were collected and
      analyzed. RESULTS: Eleven patients had acutely ruptured aneurysms with SAH.
      Clinical follow-up was available on all cases with imaging follow-up at 6 months
      in 9 patients. Two patients died from rebleeding during the acute illness. There
      was no other procedural or delayed significant symptomatic morbidity. Eight
      aneurysms were occluded with a single case of residual body filling. CONCLUSIONS:
      PED should be used in SAH with caution, reserved for suitable patients
      concomitantly treated with endosaccular coiling if possible.

PMID- 22135133
TI  - Generalized spatiotemporal myocardial strain analysis for DENSE and SPAMM
      imaging.
AB  - Displacement encoding using stimulated echoes (DENSE) and spatial modulation of
      magnetization (SPAMM) are MRI techniques for quantifying myocardial displacement
      and strain. However, DENSE has not been compared against SPAMM in phantoms
      exhibiting nonhomogeneous strain, and interobserver variability has not been
      compared between DENSE and SPAMM. To perform these comparisons, there is a need
      for a generalized analysis framework for the evaluation of myocardial strain. A
      spatiotemporal mathematical model was used to represent myocardial geometry and
      motion. The model was warped to each frame using tissue displacement maps
      calculated from either automated phase unwrapping (DENSE) or nonrigid
      registration (SPAMM). Strain and motion were then calculated from the model using
      standard methods. DENSE and SPAMM results were compared in a deformable gel
      phantom exhibiting known nonhomogeneous strain, and interobserver errors were
      determined in 19 healthy human volunteers. Nonhomogeneous strain in the phantom
      was accurately quantified using both DENSE and SPAMM. In the healthy volunteers,
      DENSE produced better interobserver errors than SPAMM for radial strain (-0.009
      +/- 0.069 vs. 0.029 +/- 0.152, respectively, bias +/- 95% confidence interval).
      In conclusion, generalized spatiotemporal modeling enables robust myocardial
      strain analysis for DENSE or SPAMM.

PMID- 22135134
TI  - Prenatal programming of adult mineral metabolism: relevance to blood pressure,
      dietary prevention strategies, and cardiovascular disease.
AB  - OBJECTIVES: Mounting evidence indicates that adult health outcomes such as the
      development of cardiovascular disease or diabetes can trace some of their roots
      back to prenatal development. This study investigated the epigenetic impact of a
      particular prenatal hormonal condition on specific health-related consequences,
      i.e., on concentrations of minerals and mineral metabolism in adults. METHODS: In
      70 university students, the second-to-fourth digit length (2D:4D) was measured as
      a proxy of prenatal sex steroid action, and the concentrations of sodium (Na),
      potassium (K), magnesium (Mg), and calcium (Ca) were determined in hair samples
      by inductively coupled plasma-mass spectrometry. Mineral concentrations and the
      mineral ratios Na/K, Na/Mg, and Na/Ca were analyzed in multivariate analyses of
      variance, with digit ratios and sex of participants as grouping variables. The
      results were validated in a replication cohort from the general population, and
      with a wider age-range. In addition, the correlation of mineral concentrations
      and mineral ratios with blood pressure was examined. RESULTS: Men with relatively
      lower (i.e., more masculine) and women with relatively higher (i.e., more
      feminine) digit ratios had higher Na/K, Na/Mg, and Na/Ca ratios than their
      counterparts. Virtually identical results were obtained in the replication study.
      Moreover, Na concentrations and Na/K ratios were significantly correlated with
      systolic blood pressure. CONCLUSIONS: The findings suggest that the individual
      variation in mineral metabolism can be predicted by 2D:4D, indicating that
      prenatal sex steroid action may be involved in the epigenetic programming of
      specific metabolic conditions which are highly relevant to adult health and
      disease.

PMID- 22135135
TI  - Cross-amyloid interaction of Abeta and IAPP at lipid membranes.

PMID- 22135138
TI  - Introduction to the special issue on the microenvironment of bone metastasis.

PMID- 22135136
TI  - Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody
      positive versus antimitochondrial autoantibody-negative primary biliary
      cirrhosis.
AB  - Substantial evidence supports dysregulated B-cell immune responses in patients
      with primary biliary cirrhosis (PBC), including the presence of serum
      antimitochondrial antibodies (AMAs). However, recent reports from murine models
      of PBC suggest that B cells may also provide regulatory function, and indeed the
      absence of B cells in such models leads to exacerbation of disease. The vast
      majority of patients with PBC have readily detectable AMAs, but a minority (<5%)
      are AMA negative (AMA(-)), even with recombinant diagnostic technology. This
      issue prompted us to examine the nature of B-cell infiltrates surrounding the
      portal areas in AMA-positive (AMA(+)) and AMA(-) patients, because they display
      indistinguishable clinical features. Of importance was the finding that the
      degree of bile duct damage around the portal areas was significantly milder in
      AMA(+) PBC than those observed in AMA(-) PBC patients. The portal areas from AMA(
      ) patients had a significant increase of cluster of differentiation (CD)5(+)
      cells infiltrating the ductal regions, and the levels of B-cell infiltrates were
      worse in the early phase of bile duct damage. The frequency of positive portal
      areas and the magnitude of CD5(+) and CD20(+) cellular infiltrates within areas
      of ductal invasion is associated with the first evidence of damage of biliary
      duct epithelia, but becomes reduced in the ductopenia stage, with the exception
      of CD5(+) cells, which remain sustained and predominate over CD20(+) cells.
      CONCLUSION: Our data suggest a putative role of B-cell autoimmunity in regulating
      the portal destruction characteristic of PBC.

PMID- 22135137
TI  - Short-term additional enfuvirtide therapy is associated with a greater
      immunological recovery in HIV very late presenters: a controlled pilot study.
AB  - OBJECTIVES: To evaluate whether the addition of enfuvirtide to standard highly
      active antiretroviral therapy (HAART) could confer immunovirological benefits in
      human immunodeficiency virus (HIV)-infected very late presenters. The current
      study is an open comparative therapeutic trial of standard protease inhibitor
      (PI)-based HAART +/- additional enfuvirtide in treatment-naive deeply
      immunologically impaired HIV-positive patients. METHODS: Very late presenters
      (CD4 <50/mm(3)), without tuberculosis and neoplasms, were alternatively allocated
      to two nucleoside reverse transcriptase inhibitors (NRTIs) and
      lopinavir/ritonavir without (control arm, CO) or with (ENF arm) enfuvirtide 90 mg
      bid. Enfuvirtide was administered until the achievement of viral load <50
      copies/ml and for at least 24 weeks. The primary objective was the magnitude of
      CD4+ cell recovery at 6 months. HIV RNA was intensively monitored in the first
      month, and, thereafter, monthly, as for CD4+ cell count and percentage, clinical
      data, and plasma drug concentrations. RESULTS: Of 22 enrolled patients (11 per
      arm), 19 completed the study (10 in the ENF arm). Baseline CD4+ cell counts and %
      were comparable, with 20 CD4+/mm(3) (12-37) and a percentage of 3.3 (1.7-7.1) in
      the ENF arm, and 16 CD4+/mm(3) (9-29) and a percentage of 3.1 (2.3-3.8) in the CO
      arm, respectively. The baseline viral load was also comparable between the two
      arms, with 5.77 log10 (5.42-6) and 5.39 log10 (5.06-6) in the ENF and CO arms,
      respectively. Enfuvirtide recipients had higher CD4+ percentage at week 8 (7.6
      vs. 3.6%, p = 0.02) and at week 24 (10.7 vs. 5.9%, p = 0.02), and a greater CD4+
      increase at week 24 (207 vs. 134 cells/mm(3), p = 0.04), with 70% of enfuvirtide
      intakers versus 12.5% of controls who achieved a CD4+ cell count >200/mm(3) (p =
      0.01). At 48 weeks, patients in the ENF arm had CD4+ cell counts higher than
      controls (251 vs. 153cells/mm(3), p = 0.04) and were also found to be faster in
      reaching a CD4 cell count over 200/mm(3): 18 (8-24) versus 48 (36-108) weeks (p =
      0.01). Viral load decay at week 4 was greater in the ENF arm (-3 vs. -2.2 log, p
      = 0.04), while the proportion of patients with viral load <50 copies/ml at week
      24 was comparable. CONCLUSIONS: In this pilot study, the addition of enfuvirtide
      to a lopinavir-based HAART was shown to be associated with a significantly faster
      and greater immunological recovery in newly discovered HIV-positive patients with
      very low CD4+ cell counts. Induction strategies using an enfuvirtide-based
      approach in such subjects warrant further investigation.

PMID- 22135139
TI  - Hydrogel photonic sensor for the detection of 3-pyridinecarboxamide.
AB  - Molecular imprinting is recognized as a powerful technique for preparing
      polymeric structures that contains tailor-made recognition sites for certain
      molecules. By combining a responsive hydrogel photonic crystal and molecular
      imprinting of 3-pyridinecarboxamide, polyacrylamide (PAM) imprinted photonic
      crystals (IPCs) with an inverse opal structure were prepared. They showed a
      rapid, recoverable, and selective response to 3-pyridinecarboxamide, which was
      detected by measuring the diffraction peak. The position of the diffraction peak
      could be tuned by copolymerizing acrylamide (AM) with acrylic acid (AA), by
      changing the ratio of AM to AA, by adding N,N'-methylene bisacrylamide to the
      monomers, or by imprinting molecules to monomers. More interestingly, the change
      in the Bragg diffraction of the IPCs can be directly converted into a readable
      optical signal that is visible to the naked eye without any labeling treatment.

PMID- 22135140
TI  - Statins and sepsis - scientifically interesting but clinically inconsequential.

PMID- 22135141
TI  - Assessment of right ventricle volumes and function by cardiac MRI: quantification
      of the regional and global interobserver variability.
AB  - Reproducibility of the manual assessment of right ventricle volumes by short-axis
      cine-MRI remains low and is often attributed to the difficulty in separating the
      right atrium from the ventricle. This study was designed to evaluate the regional
      interobserver variability of the right ventricle volume assessment to identify
      segmentation zones with the highest interobserver variability. Short-axis views
      of 90 right ventricles (30 hypertrophic, 30 dilated, and 30 normal) were acquired
      with 2D steady-state free precession sequences at 1.5 T and were manually
      segmented by two observers. The two segmentations were compared and the
      variations were quantified with a variation score based on the Hausdorff distance
      between the two segmentations and the interobserver 95% limits of concordance of
      the global volumes. The right ventricles were semiautomatically split into four
      subregions: apex, mid-ventricle, tricuspid zone, and infundibulum. These four
      subregions represented 11%, 34%, 36%, and 19% of the volume but, respectively,
      yielded variation scores of 8%, 16%, 42%, and 34%. The infundibulum yielded the
      highest interobserver regional variability although its variation score remained
      comparable to the tricuspid zone due to its lower volume. These results emphasize
      the importance of standardizing the segmentation of the infundibulum and the
      tricuspid zone to improve reproducibility.

PMID- 22135142
TI  - Active foot synovitis in patients with rheumatoid arthritis: applying clinical
      criteria for disease activity and remission may result in underestimation of foot
      joint involvement.
AB  - OBJECTIVE: To determine whether application of criteria for remission in
      rheumatoid arthritis (RA) may result in underestimation of foot joint involvement
      among patients in a clinic setting. METHODS: RA patients (n = 123) were assessed
      at baseline and 6 months after commencement of a response-driven combination
      disease-modifying antirheumatic drug (DMARD) protocol. Remission was assessed
      using disease activity measures (the 28-joint Disease Activity Score using the
      erythrocyte sedimentation rate [DAS28-ESR], Simplified Disease Activity Index
      [SDAI], and Clinical Disease Activity Index [CDAI]) as well as Boolean-based
      criteria for remission (the 1981 American College of Rheumatology [ACR]
      preliminary criteria and the 2011 ACR/European League Against Rheumatism [EULAR]
      provisional criteria). The prevalence of foot synovitis and the mean
      swollen/tender foot joint count in RA patients meeting any of these remission
      criteria were estimated by hurdle (mixed distribution) regression. RESULTS: In
      patients who received 6 months of combination DMARD treatment, application of the
      1981 ACR criteria and the newly proposed 2011 ACR/EULAR criteria, each utilizing
      full joint counts (which includes assessment of the feet), classified the least
      number of patients as being in remission (8-10%), and evidence of foot synovitis
      was minimal among these patients. In contrast, ongoing foot synovitis was present
      in a substantial proportion of patients (>20%) meeting the 28-joint count
      criteria for remission, including the DAS28-ESR, SDAI, CDAI, and 2011 ACR/EULAR
      criteria (clinical practice setting or clinical trials). Furthermore, applying
      the 2011 ACR/EULAR composite remission criterion of a SDAI score <=3.3 to define
      remission did not adequately capture the resolution of foot synovitis (i.e.,
      residual foot involvement was still detected in a substantial proportion of
      patients classified as being in remission by this definition). CONCLUSION:
      Although the DAS28-ESR, CDAI, and SDAI have been validated for assessment of
      remission in RA, this study shows that the performance of these 3 disease
      activity measures, which do not provide a direct assessment of the foot, in
      detecting foot synovitis is poor, in contrast to that of the 1981 ACR and 2011
      ACR/EULAR remission criteria utilizing full joint counts. Thus, patients may be
      at risk of ongoing damage if treatment decisions are made solely on the basis of
      criteria that omit foot joint assessment.

PMID- 22135143
TI  - Effect of microcystin-LR on protein phosphatase 2A and its function in human
      amniotic epithelial cells.
AB  - Due to their toxicity, the increased distribution of microcystins (MCs) has
      become an important worldwide problem. MCs have been recognized as inhibitors of
      protein phosphatase 2A (PP2A) through their binding to the PP2A catalytic
      subunit. However, the exact mechanism of MC toxicity has not been elucidated,
      especially concerning the cellular response and its autoregulation. To further
      dissect the role of PP2A in MC-induced toxicity, the present study was undertaken
      to determine the response of PP2A in human amniotic epithelial (FL) cells treated
      with microcystin-LR (MCLR), one of the MC congeners. The results show that a low
      dose treatment of MCLR in FL cells for 6 h induced an increase in PP2A activity,
      and a high-dose treatment of MCLR for 24 h decreased the activity of PP2A, as
      expected. The increased mRNA and protein levels of the PP2A C subunit may explain
      the increased activity of PP2A. Furthermore, MCLR altered microtubule post
      translational modifications through PP2A. These results further clarify the
      underlying mechanism how MCLR affects PP2A and may be helpful for elucidating the
      complex toxicity of MCLR.

PMID- 22135144
TI  - Red pigment production by Penicillium purpurogenum GH2 is influenced by pH and
      temperature.
AB  - The combined effects of pH and temperature on red pigment production and fungal
      morphology were evaluated in a submerged culture of Penicillium purpurogenum GH2,
      using Czapek-Dox media with d-xylose as a carbon source. An experimental design
      with a factorial fix was used: three pH values (5, 7, and 9) and two temperature
      levels (24 and 34  degrees C) were evaluated. The highest production of red
      pigment (2.46 g/L) was reached with a pH value of 5 and a temperature of 24 
      degrees C. Biomass and red pigment production were not directly associated. This
      study demonstrates that P. purpurogenum GH2 produces a pigment of potential
      interest to the food industry. It also shows the feasibility of producing and
      obtaining natural water-soluble pigments for potential use in food industries. A
      strong combined effect (p<0.05) of pH and temperature was associated with maximal
      red pigment production (2.46 g/L).

PMID- 22135145
TI  - Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and
      cell morphology of the temporal lobe.
AB  - In order to investigate the physiological effects of airport noise exposure on
      organisms, in this study, we exposed Sprague-Dawley rats in soundproof chambers
      to previously recorded aircraft-related noise for 65 d. For comparison, we also
      used unexposed control rats. Noise was arranged according to aircraft flight
      schedules and was adjusted to its weighted equivalent continuous perceived noise
      levels (L(WECPN)) of 75 and 80 dB for the two experimental groups. We examined
      rat behaviors through an open field test and measured the concentrations of
      plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric
      detection (HPLC-FLD). We also examined the morphologies of neurons and synapses
      in the temporal lobe by transmission electron microscopy (TEM). Our results
      showed that rats exposed to airport noise of 80 dB had significantly lower line
      crossing number (P<0.05) and significantly longer center area duration (P<0.05)
      than control animals. After 29 d of airport noise exposure, the concentration of
      plasma NE of exposed rats was significantly higher than that of the control group
      (P<0.05). We also determined that the neuron and synapsis of the temporal lobe of
      rats showed signs of damage after aircraft noise of 80 dB exposure for 65 d. In
      conclusion, exposing rats to long-term aircraft noise affects their behaviors,
      plasma NE levels, and cell morphology of the temporal lobe.

PMID- 22135147
TI  - Gastric motility functional study based on electrical bioimpedance measurements
      and simultaneous electrogastrography.
AB  - For some time now, the research on gastric motility and function has fallen
      behind in the amount of research on gastric endocrine, exocrine secretion, and
      gastric morphology. In this paper, a noninvasive method to study gastric motility
      was developed, taking bioimpedance measurements over the gastric area
      simultaneously with the electrogastrography (EGG). This is based on the concept
      of observing and analyzing simultaneously the intrinsic electrical gastric
      activity (basic electric rhythm) and the mechanical gastric activity.
      Additionally, preliminary clinical studies of healthy subjects and subjects with
      functional dyspepsia (FD) and gastritis were carried out. The impedance gastric
      motility (IGM) measurements of the healthy and FD subjects were compared, along
      with the studies of the FD subjects before treatment and after one week and three
      weeks of treatment. We also compared IGM measurements of healthy subjects and
      subjects with erosive gastritis, along with the studies of the subjects with
      erosive gastritis before treatment and after one week of treatment. Results show
      that FD subjects have poor gastric motility (P<0.01). After a week of treatment,
      the gastric motility of FD subjects was not yet improved although the EGG had
      returned to normal by this time. By three weeks of treatment, the regular IGM
      rhythm returned in FD subjects. There was a significant difference of IGM
      parameters between the gastritis and healthy subjects (P<0.05). The EGG rhythm of
      the gastritis subjects returned to normal at one week post-treatment, while IGM
      parameters showed a trend to improvement (P>0.05), These results suggest the
      possibility of clinic application of the proposed method.

PMID- 22135146
TI  - An efficient method of addressing ectopic beats: new insight into data
      preprocessing of heart rate variability analysis.
AB  - Heart rate variability (HRV) analysis is affected by ectopic beats. An efficient
      method was proposed to deal with the ectopic beats. The method was based on trend
      correlation of the heart timing signal. Predictor of R-R interval (RRI) value at
      ectopic beat time was constructed by the weight calculation and the slope
      estimation of preceding normal RRI. The type of ectopic beat was detected and
      replaced by the predictor of RRI. The performance of the simulated signal after
      ectopic correction was tested by the standard value using power spectrum density
      (PSD) estimation, whereas the results of clinical data with ectopic beats were
      compared with the adjacent ectopic-free data. The result showed the frequency
      indexes after ectopy corrected had less error than other methods with the test of
      simulated signal and clinical data. It indicated our method could improve the PSD
      estimation in HRV analysis. The method had advantages of high accuracy and real
      time properties to recover the sinus node modulation.

PMID- 22135148
TI  - Three-dimensional evaluation of upper anterior alveolar bone dehiscence after
      incisor retraction and intrusion in adult patients with bimaxillary protrusion
      malocclusion.
AB  - OBJECTIVE: The purpose of this study was to evaluate three-dimensional (3D)
      dehiscence of upper anterior alveolar bone during incisor retraction and
      intrusion in adult patients with maximum anchorage. METHODS: Twenty adult
      patients with bimaxillary dentoalveolar protrusion had the four first premolars
      extracted. Miniscrews were placed to provide maximum anchorage for upper incisor
      retraction and intrusion. A computed tomography (CT) scan was performed after
      placement of the miniscrews and treatment. The 3D reconstructions of pre- and
      post-CT data were used to assess the dehiscence of upper anterior alveolar bone.
      RESULTS: The amounts of upper incisor retraction at the edge and apex were
      (7.64+/-1.68) and (3.91+/-2.10) mm, respectively, and (1.34+/-0.74) mm of upper
      central incisor intrusion. Upper alveolar bone height losses at labial alveolar
      ridge crest (LAC) and palatal alveolar ridge crest (PAC) were 0.543 and 2.612 mm,
      respectively, and the percentages were (6.49+/-3.54)% and (27.42+/-9.77)%,
      respectively. The shape deformations of LAC-labial cortex bending point (LBP) and
      PAC-palatal cortex bending point (PBP) were (15.37+/-5.20) degrees  and (6.43+/
      3.27) degrees , respectively. CONCLUSIONS: Thus, for adult patients with
      bimaxillary protrusion, mechanobiological response of anterior alveolus should be
      taken into account during incisor retraction and intrusion. Pursuit of maximum
      anchorage might lead to upper anterior alveolar bone loss.

PMID- 22135149
TI  - Sociodemographic characteristics and risk factor analysis of Demodex infestation
      (Acari: Demodicidae).
AB  - To identify sociodemographic characteristics and risk factor of Demodex
      infestation, 756 students aged 13-22 years in Xi'an, China were sampled for the
      school-based cross-sectional study. Demodex was examined using the cellophane
      tape method (CTP). The results showed that the total detection rate of Demodex
      was 67.6%. Logistic regression analysis revealed that five variables (gender,
      residence, sharing sanitary ware, frequency of face-wash per day, and use of
      facial cleanser) were found to be uncorrelated with Demodex infestation, whereas
      three variables (age, skin type, and skin disease) were found to be independent
      correlates. Students aged over 18 years had 22.1 times higher odds of Demodex
      infestation compared to those under 16 years and students aged 16-18 years also
      had 2.1 times higher odds compared to those aged 13-15 years. Odds of having a
      Demodex infestation for oily or mixed skin were 2.1 times those for dry or
      neutral skin. Students with a facial skin disease had 3.0 times higher odds of
      being infested with Demodex compared to those without. The inception rate of
      students with facial dermatoses increased in parallel with increasing mite count.
      The inception rates were 21.3%, 40.7%, 59.2%, and 67.7% in the negative, mild,
      moderate, and severe infestation groups, respectively (chi(2)=60.6, P<0.001).
      Specifically, the amount of infested mites and inception rate of acne vulgaris
      were positively correlated (R(2)=0.57, moderate infestation odds ratio (OR)=7.1,
      severe infestation OR=10.3). It was concluded that Demodex prevalence increases
      with age, and Demodex presents in nearly all adult human. Sebaceous hyperplasia
      with oily or mixed skin seems to favour Demodex proliferation. Demodex
      infestation could be associated with acne vulgaris. The CTP is a good sampling
      method for studies of Demodex prevalence.

PMID- 22135150
TI  - Facial dermatosis associated with Demodex: a case-control study.
AB  - Demodex has been considered to be related with multiple skin disorders, but
      controversy persists. In this case-control study, a survey was conducted with 860
      dermatosis patients aged 12 to 84 years in Xi'an, China to identify the
      association between facial dermatosis and Demodex. Amongst the patients, 539
      suffered from facial dermatosis and 321 suffered from non-facial dermatosis.
      Demodex mites were sampled and examined using the skin pressurization method.
      Multivariate regression analysis was applied to analyze the association between
      facial dermatosis and Demodex infestation, and to identify the risk factors of
      Demodex infestation. The results showed that total detection rate of Demodex was
      43.0%. Patients aged above 30 years had higher odds of Demodex infestation than
      those under 30 years. Compared to patients with neutral skin, patients with
      mixed, oily, or dry skin were more likely to be infested with Demodex (odds
      ratios (ORs) were 2.5, 2.4, and 1.6, respectively). Moreover, Demodex infestation
      was found to be statistically associated with rosacea (OR=8.1), steroid-induced
      dermatitis (OR=2.7), seborrheic dermatitis (OR=2.2), and primary irritation
      dermatitis (OR=2.1). In particular, ORs calculated from the severe infestation
      (>=5 mites/cm(2)) rate were significantly higher than those of the total rate.
      Therefore, we concluded that Demodex is associated with rosacea, steroid-induced
      dermatitis, seborrheic dermatitis, and primary irritation dermatitis. The rate of
      severe infestation is found to be more correlated with various dermatosis than
      the total infestation rate. The risk factors of Demodex infestation, age, and
      skin types were identified. Our study also suggested that good hygiene practice
      might reduce the chances of demodicosis and Demodex infestation.

PMID- 22135151
TI  - Different effects of L-arginine on morphine tolerance in sham and ovariectomized
      female mice.
AB  - OBJECTIVE: The roles of gonadal hormones and nitric oxide (NO) on the analgesic
      effects of morphine, tolerance to morphine, and their interactions have been
      widely investigated. In the present study, the effect of L-arginine (an NO
      precursor) on morphine tolerance in sham and ovariectomized (OVX) female mice was
      investigated. METHODS: Forty mice were divided into sham and OVX groups. On the
      first day, a hot plate test ((55+/-0.2)  degrees C; cut-off 30 s) was carried out
      as a base record 15 min before injection of morphine (10 mg/kg, subcutaneously
      (s.c.)) and was repeated every 15 min after injection. The sham group was then
      divided into two subgroups: sham-tolerance-L-arginine (Sham-Tol-LA) and sham
      tolerance-saline (Sham-Tol-Sal) which received either L-arginine 50 mg/kg
      (intraperitoneally (i.p.)) or saline 10 ml/kg (i.p.), respectively, three times
      in a day for three consecutive days. Morphine tolerance was induced in animals by
      injecting 30 mg/kg morphine (s.c.) three times/day for three days. This treatment
      was also used for OVX subgroups. On the fifth day, the hot plate test was
      repeated. The analgesic effect of morphine was calculated as the maximal percent
      effect (MPE). The results were compared using repeated measure analysis of
      variance (ANOVA). RESULTS: There was no significant difference in MPE between the
      OVX and sham groups. The MPEs in both the Sham-Tol-Sal and OVX-Tol-Sal groups
      were lower than those in both the sham and OVX groups (P<0.01). The MPE in the
      OVX-Tol-Sal group was greater than that in the Sham-Tol-Sal group (P<0.01). The
      MPE in the Sham-Tol-LA group was higher than that in the Sham-Tol-Sal group
      (P<0.01). However, there was no significant difference between the Sham-Tol-LA
      and sham groups or between the OVX-Tol-LA and OVX-Tol-Sal groups. CONCLUSIONS:
      The results of the present study showed that repeated administration of morphine
      causes tolerance to the analgesic effect of morphine. L-arginine could prevent
      tolerance to morphine but its effect was different in the presence of ovarian
      hormones.

PMID- 22135152
TI  - Cordyceps cicadae extracts ameliorate renal malfunction in a remnant kidney
      model.
AB  - BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is a growing public
      health problem with an urgent need for new pharmacological agents. Cordyceps
      cicadae is widely used in traditional Chinese medicine (TCM) and has potential
      renoprotective benefits. The current study aimed to determine any scientific
      evidence to support its clinical use. METHODS: We analyzed the potential of two
      kinds of C. cicadae extract, total extract (TE) and acetic ether extract (AE), in
      treating kidney disease simulated by a subtotal nephrectomy (SNx) model. Sprague
      Dawley rats were divided randomly into seven groups: sham-operated group, vehicle
      treated SNx, Cozaar, 2 g/(kg?d) TE SNx, 1 g/(kg?d) TE SNx, 92 mg/(kg?d) AE SNx,
      and 46 mg/(kg?d) AE SNx. Renal injury was monitored using urine and serum
      analyses, and hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) stainings
      were used to analyze the level of fibrosis. The expression of type IV collagen
      (Col IV), fibronectin (FN), transforming growth factor-beta1 (TGF-beta1), and
      connective tissue growth factor (CTGF) was detected by immunohistochemistry.
      RESULTS: Renal injury, reflected in urine and serum analyses, and pathological
      changes induced by SNx were attenuated by TE and AE intervention. The depositions
      of Col IV and FN were also decreased by the treatments and were accompanied by
      reduced expression of TGF-beta1 and CTGF. In some respects, 2 g/(kg?d) of TE
      produced better effects than Cozaar. CONCLUSIONS: For the first time, we have
      shown that C. cicadae may inhibit renal fibrosis in vivo through the TGF
      beta1/CTGF pathway. Therefore, we conclude that the use of C. cicadae could
      provide a rational strategy for combating renal fibrosis.

PMID- 22135153
TI  - Chaiqin Chengqi Decoction decreases IL-6 levels in patients with acute
      pancreatitis.
AB  - OBJECTIVE: In this paper, we investigated the effect of the traditional Chinese
      medicine Chaiqin Chengqi Decoction (CQCQD) on serum cytokines in acute
      pancreatitis (AP) patients. METHODS: Peripheral blood samples from 107 AP
      patients were collected within the first 48 h of AP onset and on the 10th day of
      CQCQD treatment. Control samples were collected from 20 healthy individuals.
      Serum proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6), and anti-inflammatory cytokines IL-10 and IL-1beta receptor
      antagonist (IL-1ra) were examined using the Luminex 100 system. RESULTS: Within
      the first 48 h of AP onset, IL-6 and IL-1ra levels in severe AP (SAP) patients
      were significantly higher than those in mild AP (MAP) patients, but IL-10 levels
      in SAP patients were significantly lower than those in MAP patients.
      Proinflammatory cytokine IL-6 was significantly decreased after CQCQD treatment
      (P<0.05), especially in SAP patients (n=25 of 36, P<0.05). The hospitalization
      time of SAP patients was shortened significantly when serum IL-6 decreased after
      CQCQD treatment (P<0.05). CONCLUSIONS: CQCQD decreased proinflammatory cytokine
      IL-6 levels in AP patients.

PMID- 22135154
TI  - The timing of antibiotics at cesarean: a randomized controlled trial.
AB  - We compared maternal and neonatal outcomes in women who received prophylactic
      antibiotics prior to skin incision to those who received antibiotics at cord
      clamp. We performed a randomized clinical trial at two sites. Eligible women
      included those undergoing nonemergency cesarean at 36 weeks' gestation or
      greater. Subjects were randomized (permuted blocks) into one of two treatments:
      "preoperative antibiotics" (cefazolin 1 g given <30 minutes prior to skin
      incision) or "intraoperative antibiotics" (cefazolin 1 g at cord clamping).
      Patients who reported an allergy to penicillin received clindamycin 900 mg. The
      trial primary outcome was a composite of maternal infectious morbidities, defined
      as having any one of the following: (1) postoperative fever (defined as oral
      temperature >38 degrees C on two separate occasions more than 6 hours apart,
      after the initial 24-hour postoperative period); (2) wound infection (defined as
      purulent discharge from the incision); (3) endomyometritis (defined as fundal
      tenderness and fever malodorous lochia, fever); (4) urinary tract infection
      (defined as fever, positive urine culture). We enrolled a total of 434 subjects
      in this study, with 217 in each group. Overall, we found no difference in
      composite maternal infectious morbidity between those who received antibiotics
      preoperatively and those who received antibiotics at cord clamp (relative risk =
      1.2, 95% confidence interval 0.7 to 1.5). Neonatal outcomes were also similar
      between the two intervention arms. The rate of suspected sepsis was similar
      between the two groups. There were no cases of antibiotic resistance in the
      neonates. Either preoperative antibiotic therapy or antibiotic administration
      after cord clamp is a reasonable clinical method for reducing the risk of
      postcesarean infectious morbidity.

PMID- 22135155
TI  - Improved least squares MR image reconstruction using estimates of k-space data
      consistency.
AB  - This study describes a new approach to reconstruct data that has been corrupted
      by unfavorable magnetization evolution. In this new framework, images are
      reconstructed in a weighted least squares fashion using all available data and a
      measure of consistency determined from the data itself. The reconstruction scheme
      optimally balances uncertainties from noise error with those from data
      inconsistency, is compatible with methods that model signal corruption, and may
      be advantageous for more accurate and precise reconstruction with many least
      squares-based image estimation techniques including parallel imaging and
      constrained reconstruction/compressed sensing applications. Performance of the
      several variants of the algorithm tailored for fast spin echo and self-gated
      respiratory gating applications was evaluated in simulations, phantom
      experiments, and in vivo scans. The data consistency weighting technique
      substantially improved image quality and reduced noise as compared to traditional
      reconstruction approaches.

PMID- 22135156
TI  - Incidence and risk factors for radiographic knee osteoarthritis and knee pain in
      Japanese men and women: a longitudinal population-based cohort study.
AB  - OBJECTIVE: To examine the incidence and progression of radiographic knee
      osteoarthritis (OA) and the incidence of knee pain, and their risk factors in
      Japan, using the large-scale population of the nationwide cohort study ROAD
      (Research on Osteoarthritis/osteoporosis Against Disability). METHODS: Subjects
      from the ROAD study who had been recruited in 2005-2007 were followed up with
      knee radiography 3 years later. A total of 2,262 paired radiographs (74.4% of the
      original sample) were scored using the Kellgren/Lawrence (K/L) grading system,
      and the incidence and progression rate of knee OA was examined. The incidence
      rate of knee pain was also examined. In addition, risk factors were tested for
      their association with incident and progressive radiographic knee OA and incident
      knee pain. RESULTS: Given the ~3.3-year followup, the rate of incident K/L grade
      >=2 radiographic knee OA was 6.9% and 11.9% in men and women, respectively, while
      that of K/L grade >=3 knee OA was 8.4% and 13.9% in men and women, respectively.
      The rate of progressive knee OA was 17.8% and 22.3% in men and women,
      respectively. The incident rate of knee pain was 21.2% and 27.3% in men and
      women, respectively. Female sex was a risk factor for incident K/L grade >=2 knee
      OA, but was not associated with incident K/L grade >=3 knee OA or progressive
      knee OA. Knee pain was a risk factor for incident and progressive knee OA.
      Previous knee injury was a risk factor for knee pain but not for radiographic
      knee OA. CONCLUSION: The present longitudinal study revealed a high incidence of
      radiographic knee OA in Japan.

PMID- 22135157
TI  - Herbert Mayr.

PMID- 22135158
TI  - Proceedings of the human biology association 36th annual meeting, Hilton
      Minneapolis, Minneapolis, MN.

PMID- 22135159
TI  - Sequential alterations of microRNA expression in hepatocellular carcinoma
      development and venous metastasis.
AB  - Hepatocellular carcinoma (HCC) is a prevalent cancer with an extremely high
      mortality rate attributed to HCC metastasis, which is the major cause of tumor
      recurrence and organ failure. Presence of tumor thrombi in the portal veins
      (venous metastases) is a clinicopathological feature of metastatic HCCs. In this
      study, we analyzed the microRNA (miRNA) expression profiles of nontumorous
      livers, primary HCCs, and venous metastases in the same livers from 20 HCC
      patients by way of TaqMan low-density array (TLDA) and identified the precise
      alterations of miRNA expression from nontumorous livers to primary HCCs and
      venous metastases globally. By unsupervised clustering analysis, nontumorous
      livers were distinctly segregated from primary HCCs and venous metastases,
      whereas no discernible difference in the expression pattern could be found
      between primary HCCs and venous metastases. However, a marked global reduction of
      miRNA expression levels was detected in venous metastases, as compared with
      primary HCCs. These data suggest that miRNA deregulation is an early event in
      liver carcinogenesis and the later global miRNA down-regulation aggravates the
      preexisting miRNA deregulation to further promote HCC metastasis. CONCLUSION: Our
      study has enriched the current understanding of the deregulation of miRNAs in HCC
      progression and highlighted the sequential and distinctive alterations of miRNA
      expression in primary HCC and venous metastasis formation.

PMID- 22135160
TI  - Selective action of metoprolol to attenuate regadenoson-induced tachycardia in
      conscious dogs.
AB  - BACKGROUND: Regadenoson is a coronary vasodilator that causes tachycardia via
      activation of the sympathetic nervous system. We determined whether beta(1)
      adrenergic blockade can attenuate tachycardia without significantly reducing
      coronary vasodilation induced by regadenoson. METHODS AND RESULTS: Hemodynamics
      and coronary blood flow (CBF) were measured in conscious dogs. Baseline CBF and
      heart rate (HR) were 42 +/- 2 mL/min and 87 +/- 8 bpm (mean +/- SEM),
      respectively. Regadenoson (1, 2.5, and 5 MUg/kg) increased peak CBF by 129 +/-
      10, 149 +/- 7, and 174 +/- 10 mL/min and HR by 48 +/- 6, 67 +/- 5, and 85 +/- 11
      bpm, respectively, (all P < .05 vs baseline). In the presence of metoprolol (1.5
      mg/kg), the peak increases in CBF caused by these three doses of regadenoson were
      reduced by only 11 +/- 7%, 10 +/- 4%, and 21 +/- 2% (P = NS, <.05, and <.05 vs
      regadenoson alone), respectively, whereas the regadenoson-induced tachycardia was
      significantly reduced by 55 +/- 8%, 55 +/- 4%, and 52 +/- 5% (all P < .05). In
      the presence of metoprolol, the duration of the regadenoson-induced increase in
      CBF was reduced, but the duration of the 2-fold increase in CBF caused by 5
      MUg/kg regadenoson was still nearly 6 minutes. CONCLUSION: beta(1)-Adrenergic
      blockade with metoprolol attenuated the regadenoson-induced increase in HR more
      than the increase in CBF.

PMID- 22135161
TI  - Treatment of familial hypercholesterolemia: is there a need beyond statin
      therapy?
AB  - Familial hypercholesterolemia (FH) is a genetic lipid disorder that is
      characterized by severely elevated cholesterol levels and premature
      cardiovascular disease. Both the heterozygous and homozygous forms of FH require
      aggressive cholesterol-lowering therapy. Statins alone frequently do not lower
      these patients' cholesterol to therapeutic levels, and some patients are
      intolerant to statins. Combination or monotherapy with other current
      pharmacotherapies are options, but even with these some FH patients do not meet
      their low-density lipoprotein (LDL) cholesterol goals. In the cases of statin
      intolerance, LDL apheresis may be another treatment option. There are currently
      several novel therapies in development for LDL lowering that target either
      production or catabolism of LDL, plaque regression, and potentially gene
      transfer. We conclude that there is a need beyond statins for patients with FH,
      especially in cases of statin intolerance, and when even the highest doses of
      statin do not get patients to goal cholesterol levels.

PMID- 22135162
TI  - Role of microRNAs in stem/progenitor cells and cardiovascular repair.
AB  - MicroRNAs (miRNAs), small non-coding RNAs, play a critical role in
      differentiation and self-renewal of pluripotent stem cells, as well as in
      differentiation of cardiovascular lineage cells. Several miRNAs have been
      demonstrated to repress stemness factors such as Oct4, Nanog, Sox2 and Klf4 in
      embryonic stem cells, thereby promoting embryonic stem cell differentiation.
      Furthermore, targeting of different miRNAs promotes reprogramming towards induced
      pluripotent stem cells. MicroRNAs are critical for vascular smooth muscle cell
      differentiation and phenotype regulation, and miR-143 and miR-145 play a
      particularly important role in this respect. Notably, these miRNAs are down
      regulated in several cardiovascular disease states, such as in atherosclerotic
      lesions and vascular neointima formation. MicroRNAs are critical regulators of
      endothelial cell differentiation and ischaemia-induced neovascularization. miR
      126 is important for vascular integrity, endothelial cell proliferation and
      neovascularization. miR-1 and miR-133 are highly expressed in cardiomyocytes and
      their precursors and regulate cardiomyogenesis. In addition, miR-499 promotes
      differentiation of cardiomyocyte progenitor cells. Notably, miRNA expression is
      altered in cardiovascular disease states, and recent studies suggest that
      dysregulated miRNAs may limit cardiovascular repair responses. Dysregulation of
      miRNAs may lead to an altered function and differentiation of cardiovascular
      progenitor cells, which is also likely to represent a limitation of autologous
      cell-based treatment approaches in these patients. These findings suggest that
      targeting of specific miRNAs may represent an interesting novel opportunity to
      impact on endogenous cardiovascular repair responses, including effects on
      stem/progenitor cell differentiation and functions. This approach may also serve
      to optimize cell-based treatment approaches in patients with cardiovascular
      disease.

PMID- 22135163
TI  - IkappaBNS regulates interleukin-6 production and inhibits neointimal formation
      after vascular injury in mice.
AB  - AIMS: IkappaBNS regulates a subset of Toll-like receptor (TLR)-dependent genes
      including interleukin-6 (IL-6) by inhibiting nuclear factor-kappaB (NF-kappaB).
      IL-6 is an inflammatory biomarker for cardiovascular diseases. The aim of this
      study was to determine whether IkappaBNS changes arterial inflammation and
      intimal hyperplasia after vascular injury. METHODS AND RESULTS: We investigated
      neointimal formation in IkappaBNS-deficient (IkappaBNS(-/-); C57BL/6 background)
      and wild-type (IkappaBNS(+/+)) mice 2 weeks after cuff injury. The mean intimal
      area and the intima/media ratio of IkappaBNS(-/-) mice increased 89% (8066 +/-
      1141 vs. 4267 +/- 1095 MUm(2); P = 0.027) and 100% (0.72 +/- 0.13 vs. 0.36 +/-
      0.09; P = 0.032) compared with IkappaBNS(+/+) mice. We observed significant up
      regulation of TLR4 in injured arteries of IkappaBNS(-/-) mice. NF-kappaB activity
      in the intima of IkappaBNS(-/-) mice was 5.1-fold higher (P = 0.008) compared
      with IkappaBNS(+/+) mice at 7 days post-injury. IL-6 mRNA levels in injured
      arteries of IkappaBNS(-/-) mice were 1.8-fold higher (P = 0.002) compared with
      those of IkappaBNS(+/+) mice at 3 days post-injury. Vascular smooth muscle cells
      from IkappaBNS(-/-) mice showed a significant increase in cell migration compared
      with those from IkappaBNS(+/+) mice after IL-6 stimulation in the scratch-wound
      healing assay. Furthermore, anti-mouse IL-6 receptor antibody (MR16-1)
      significantly reduced intimal hyperplasia compared with control IgG injection in
      IkappaBNS(-/-) mice. These findings suggest that IL-6 participates in the
      development of neointimal hyperplasia after vascular injury in IkappaBNS(-/-)
      mice. CONCLUSION: IkappaBNS down-regulates TLR4 expression, NF-kappaB activity,
      and IL-6 production after vascular injury. IkappaBNS might suppress intimal
      hyperplasia caused by vascular inflammation such as atherosclerosis, and
      restenosis after angioplasty.

PMID- 22135165
TI  - Association between use of nicotine replacement therapy for harm reduction and
      smoking cessation: a prospective study of English smokers.
AB  - AIMS: It is important to know how far smokers' attempts at using nicotine
      replacement therapy (NRT) for smoking 'harm reduction' (reducing harm from
      continued smoking) promote or undermine cessation. To contribute to that goal,
      this study aimed to assess whether smokers' reports of smoking reduction (SR) and
      the use of NRT for SR and temporary abstinence (TA) predicted subsequent attempts
      to quit smoking and smoking status in a population sample. It also examined
      whether use of NRT for SR or TA was associated with reduced cigarette consumption
      compared with SR without NRT and non-use of NRT for TA. METHOD: Data were
      collected from 15 539 smokers involved in the Smoking Toolkit Study, a series of
      monthly household surveys of adults aged 16+; of whom 23% (n=3149) completed a 6
      month follow-up questionnaire. At baseline, participants were asked whether they
      were currently using NRT for SR or TA. They were also asked for demographic
      information and daily cigarette consumption. At 6-month follow-up, data on
      attempts to quit smoking and smoking status were collected. RESULTS: NRT use for
      SR and TA prospectively predicted attempts to quit smoking (OR 1.61, 95% CI 1.30
      to 2.01 and OR 1.94, 95% CI 1.56 to 2.38 for SR and TA respectively) and
      abstinence (OR 1.51, 95% CI 1.06 to 2.16 and OR 2.09, 95% CI 1.51 to 3.34 for SR
      and TA respectively) at 6-months follow-up. Use of NRT for SR or TA was
      associated with a small reduction in cigarette consumption (two cigarettes per
      day) compared with SR without NRT or non-use of NRT for TA. CONCLUSIONS: The use
      of NRT for SR or TA appears to be positively associated with subsequent attempts
      to quit smoking and abstinence among smokers in England, despite very little
      apparent effect on daily cigarette consumption. With replication, these findings
      support the potential benefit of using NRT for harm reduction but primarily as a
      means of promoting cessation.

PMID- 22135164
TI  - Energy-preserving effects of IGF-1 antagonize starvation-induced cardiac
      autophagy.
AB  - AIMS: Insulin-like growth factor 1 (IGF-1) is known to exert cardioprotective
      actions. However, it remains unknown if autophagy, a major adaptive response to
      nutritional stress, contributes to IGF-1-mediated cardioprotection. METHODS AND
      RESULTS: We subjected cultured neonatal rat cardiomyocytes, as well as live mice,
      to nutritional stress and assessed cell death and autophagic rates. Nutritional
      stress induced by serum/glucose deprivation strongly induced autophagy and cell
      death, and both responses were inhibited by IGF-1. The Akt/mammalian target of
      rapamycin (mTOR) pathway mediated the effects of IGF-1 upon autophagy.
      Importantly, starvation also decreased intracellular ATP levels and oxygen
      consumption leading to AMP-activated protein kinase (AMPK) activation; IGF-1
      increased mitochondrial Ca(2+) uptake and mitochondrial respiration in nutrient
      starved cells. IGF-1 also rescued ATP levels, reduced AMPK phosphorylation and
      increased p70(S6K) phosphorylation, which indicates that in addition to Akt/mTOR,
      IGF-1 inhibits autophagy by the AMPK/mTOR axis. In mice harbouring a liver
      specific igf1 deletion, which dramatically reduces IGF-1 plasma levels, AMPK
      activity and autophagy were increased, and significant heart weight loss was
      observed in comparison with wild-type starved animals, revealing the importance
      of IGF-1 in maintaining cardiac adaptability to nutritional insults in vivo.
      CONCLUSION: Our data support the cardioprotective actions of IGF-1, which, by
      rescuing the mitochondrial metabolism and the energetic state of cells, reduces
      cell death and controls the potentially harmful autophagic response to
      nutritional challenges. IGF-1, therefore, may prove beneficial to mitigate damage
      induced by excessive nutrient-related stress, including ischaemic disease in
      multiple tissues.

PMID- 22135166
TI  - Objective measurement of area differences in 'private' smoking behaviour:
      observing smoking in vehicles.
AB  - OBJECTIVES: The objective is to (a) refine and use methods to measure the point
      prevalence of smoking and of secondhand smoke exposure in moving vehicles and (b)
      compare these prevalences (1) between two areas of contrasting socioeconomic
      status and (2) over time. METHODS: The authors developed and tested a single
      observer method and observed the point prevalence of smoking in vehicles in
      Wellington, New Zealand. The two observation sites represented high and low areas
      of socioeconomic deprivation (based on a small area deprivation index). RESULTS:
      A total of 149 886 vehicles were observed. The mean point prevalence of smoking
      in vehicles at both sites combined was 3.2% (95% CI 3.1% to 3.3%). Of those
      vehicles with smoking, 4.1% had children present. Smoking point prevalence in
      vehicles was 3.9 times higher in the area of high deprivation than in the area of
      low deprivation (95% CI 3.6 to 4.2). The same pattern was seen for vehicles with
      only the driver at 3.6 times (95% CI 3.4 to 4.0), in vehicles with other adults
      at 4.0 times (95% CI 3.4 to 4.7) and in vehicles with children at 10.9 times (95%
      CI 6.8 to 21.3), with all results adjusted for vehicle occupancy. CONCLUSIONS:
      Observing smoking in vehicles using a single-observer method provides a feasible
      and objective indicator of the different smoking behaviours, especially around
      children, within an area. This study further supports the evidence from this
      country and internationally that adults and children from high-deprivation areas
      are much more likely to be exposed to secondhand smoke.

PMID- 22135167
TI  - Cigarette butts near building entrances: what is the impact of smoke-free college
      campus policies?
AB  - BACKGROUND: Indoor and outdoor tobacco-free campus policies for schools,
      hospitals and universities are increasingly being adopted. Yet, little direct
      evidence exists on the impact of tobacco-free campuses on tobacco outcomes.
      OBJECTIVES: To identify differences in cigarettes smoked at main campus building
      entrances by campus policy strength. METHODS: Researchers collected cigarette
      butts (n=3427) at main building entrances (n=67) at baseline and follow-up on 19
      community college campuses stratified by strength of campus outdoor tobacco
      policy (none, perimeter/designated area, 100% tobacco free). Outcome measures
      included the number of butts per day at building entrances averaged to create a
      campus score. Analysis of variance techniques examined differences in scores by
      the strength of campuses' outdoor tobacco policy. RESULTS: One hundred per cent
      tobacco-free community college campuses had significantly fewer cigarette butts
      at doors than campuses with no outdoor restrictions. Butts on community college
      campuses with partial policies were not statistically different from campuses
      with no policy or campuses with a 100% tobacco-free policy but indicated that a
      dose-response relationship may exist. CONCLUSIONS: This study provides some of
      the first evidence on the impact of 100% tobacco-free outdoor policies on college
      campuses using an objective and reproducible measure. Such policies likely
      provide a more healthful environment for students, staff, faculty and visitors.

PMID- 22135168
TI  - SA2RAGE: a new sequence for fast B1+ -mapping.
AB  - At high magnetic field strengths (>= 3T), the radiofrequency wavelength used in
      MRI is of the same order of magnitude of (or smaller than) the typical sample
      size, making transmit magnetic field (B1+) inhomogeneities more prominent.
      Methods such as radiofrequency-shimming and transmit SENSE have been proposed to
      mitigate these undesirable effects. A prerequisite for such approaches is an
      accurate and rapid characterization of the B1+ field in the organ of interest. In
      this work, a new phase-sensitive three-dimensional B1+-mapping technique is
      introduced that allows the acquisition of a 64 * 64 * 8 B1+-map in ~ 20 s,
      yielding an accurate mapping of the relative B1+ with a 10-fold dynamic range
      (0.2-2 times the nominal B1+). Moreover, the predominant use of low flip angle
      excitations in the presented sequence minimizes specific absorption rate, which
      is an important asset for in vivo B1+-shimming procedures at high magnetic
      fields. The proposed methodology was validated in phantom experiments and
      demonstrated good results in phantom and human B1+-shimming using an 8-channel
      transmit-receive array.

PMID- 22135169
TI  - Remarkably high oxide ion conductivity at low temperature in an ordered fluorite
      type superstructure.

PMID- 22135171
TI  - Systematic review and meta-analysis of the use of lightweight versus heavyweight
      mesh in open inguinal hernia repair (Br J Surg 2012; 99: 29-37).

PMID- 22135172
TI  - Randomized clinical trial of a brief psychological intervention to increase
      walking in patients with intermittent claudication (Br J Surg 2012; 99: 49-56).

PMID- 22135173
TI  - Extended surgery for advanced pancreatic endocrine tumours.
AB  - BACKGROUND: Pancreatic endocrine tumours are often diagnosed at an advanced stage
      with hepatic metastasis. This study investigated whether extended resections for
      advanced malignant pancreatic endocrine tumours influenced disease-free and
      disease-specific survival. METHODS: Patients who had curative resection of
      pancreatic endocrine tumours were analysed retrospectively for disease-free and
      disease-specific survival, with a focus on the role of extended surgical
      resection. RESULTS: Forty-one patients were included in the analysis, 13 of whom
      underwent extended surgical resection in addition to pancreatic resection. This
      included partial liver resection in nine patients, portal vein resection in
      three, partial gastric resection in five and liver transplantation in three
      patients. There were no deaths in hospital or within 30 days. Median follow-up
      was 40 (range 2-239) months. Thirty-five, 24 and 13 patients survived more than
      1, 3 and 5 years respectively. Patients who underwent extended resection had
      similar disease-specific survival to those who had pancreatic resection alone
      (hazard ratio (HR) 1.50, 95 per cent confidence interval (c.i.) 0.35 to 6.35; P =
      0.581) but with a higher frequency of complications (odds ratio (OR) 4.28, 95 per
      cent c.i. 1.04 to 17.62; P = 0.044). Among patients with liver metastases, the
      mortality rate was higher in those in whom liver resection was not possible than
      in patients who had liver resection (HR 9.24, 1.00 to 85.18; P = 0.049). Patients
      who had liver resection had similar disease-specific survival to those without
      liver metastases (HR 0.84, 0.09 to 7.57; P = 0.877). CONCLUSION: Extended
      surgical resection for locally advanced and metastatic pancreatic endocrine
      tumours is feasible with encouraging disease-specific survival.

PMID- 22135174
TI  - Assessment of haemorrhoidal artery network using colour duplex imaging and
      clinical implications (Br J Surg 2012; 99: 112-118).

PMID- 22135176
TI  - Systematic review and meta-analysis of intraoperative versus preoperative
      endoscopic sphincterotomy in patients with gallbladder and suspected common bile
      duct stones (Br J Surg 2011; 98: 908-916).

PMID- 22135177
TI  - Polymorphisms in the toll-like receptor 9 gene associated with sepsis and
      multiple organ dysfunction after major blunt trauma (Br J Surg 2011; 98: 1252
      1259).

PMID- 22135179
TI  - Effect of type of alcoholic beverage in causing acute pancreatitis (Br J Surg
      2011; 98: 1609-1616).

PMID- 22135182
TI  - [The need to revise the hemoglobin threshold value in the  German Quality
      Assurance Directive for Dialysis].
AB  - The German Quality Assurance Directive for Dialysis (QSD-RL) stipulates that no
      more than 15 % of all patients treated in a dialysis unit in any quarter may have
      a hemoglobin (Hb) value lower than 10 g/dl. For approximately 90 % of dialysis
      patients, this Hb threshold value can be simply achieved by administering
      erythropoiesis-stimulating agents (ESA). However, the question is raised as to
      wether this Hb threshold accords with the current state of knowledge. It is now
      evident from four randomized controlled trials (above all the TREAT study) and
      three meta-analyses that an ESA-induced increase in Hb does not produce any
      significant survival benefit in cases of chronic kidney disease (CKD), but may
      actually be detrimental. Critical attention must be focused in this regard on the
      higher risk of cardiovascular and cerebrovascular events, as well as malignoma
      associated risks. In 2011, in response to these findings, the American Food and
      Drug Administration (FDA), the Drug Directive (AM-RL) of the German Federal Joint
      Committee and KDIGO (Kidney Disease: Improving Global Outcomes) amended
      guidelines for the treatment of renal anemia. Very restrictive recommendations
      were made regarding the use of ESA in CKD, according to which the Hb threshold
      value of 10 g/dl stipulated in the Quality Assurance Directive is now obsolete,
      thus necessitating prompt revision of the Directive. Two alternatives are
      available in this regard: either the 10 g/dl Hb threshold value applicable
      hitherto is withdrawn without replacement, and individualized treatment of renal
      anemia is practised ("individualization") instead, or a threshold value of 9 g/dl
      (modified "standardization") is applied in future.

PMID- 22135183
TI  - A pilot study of a physical activity intervention targeted towards women at
      increased risk for breast cancer.
AB  - OBJECTIVE: The objective was to pilot test a physical activity intervention
      targeted towards women with a first-degree relative with breast cancer. METHODS:
      Sedentary women (n = 27) with at least one first-degree relative with breast
      cancer but no personal breast cancer diagnosis received a print-based physical
      activity intervention. The intervention was a 12-week theory-based and
      individually tailored physical activity intervention targeted towards women with
      a family history of breast cancer. Participants' minutes of physical activity,
      worry about breast cancer, perceived risk of developing breast cancer, and
      perceived control over breast cancer risk were assessed at baseline and 12 weeks.
      RESULTS: There was a significant increase in minutes of moderate to vigorous
      intensity physical activity from baseline to 12 weeks (t = 4.93, p < 0.001), with
      a mean increase in physical activity of 130.56 min/week (SD = 137.50). At 12
      weeks, 41% met the American College of Sports Medicine criteria of engaging in
      150 min or more of moderate intensity activity. Regression models indicate that
      change in perceived risk of breast cancer was significantly associated with
      change in physical activity (t = -2.36, p = 0.03, r = 0.34), with decreases in
      perceived risk associated with increases in physical activity over time.
      CONCLUSIONS: Findings suggest that a targeted intervention can increase physical
      activity and decrease perceived risk of breast cancer.

PMID- 22135184
TI  - The emerging role of cardiac resynchronization therapy in milder heart failure:
      are we implanting too late for response?
AB  - The role of cardiac resynchronization therapy in mild heart failure has become a
      focus of attention with the publication of recent clinical trials. We present a
      review of the data supporting implantation of cardiac resynchronization devices
      in early stage heart failure. In addition, we present evidence that may suggest
      patients are often implanted too late for clinical benefit, potentially
      contributing to the relatively high nonresponder rate seen in randomized trials
      and clinical practice.

PMID- 22135186
TI  - Evaluating heart failure after implantation of mechanical circulatory support
      devices.
AB  - The medical community has seen an explosive rise in the utilization of
      implantable mechanical circulatory support devices for late-stage cardiomyopathy.
      Care for these complex patients requires a basic understanding of device
      physiology and potential complications. This review focuses on an algorithm that
      incorporates a careful clinical history and examination with diagnostic
      modalities for the evaluation of a patient who is failing therapy with a
      continuous-flow left ventricular assist device, as well as the general management
      and optimization of patients implanted with an artificial heart.

PMID- 22135185
TI  - Pharmacogenetics in chronic heart failure: new developments and current
      challenges.
AB  - The individual patient responses to chronic heart failure (HF) pharmacotherapies
      are highly variable. This variability cannot be entirely explained by clinical
      characteristics, and genetic variation may play a role. Therefore, this review
      will summarize the background pharmacogenetic literature for major HF
      pharmacotherapy classes (ie, beta-blockers, angiotensin-converting enzyme
      inhibitors, digoxin, and loop diuretics), evaluate recent advances in the HF
      pharmacogenetic literature in the context of previous findings, and discuss the
      challenges and conclusions for HF pharmacogenetic data and its clinical
      application.

PMID- 22135187
TI  - Variants in ABCB1, TGFB1, and XRCC1 genes and susceptibility to viral hepatitis A
      infection in Mexican Americans.
AB  - Hepatitis A vaccination has dramatically reduced the incidence of hepatitis A
      virus (HAV) infection, but new infections continue to occur. To identify human
      genetic variants conferring a risk for HAV infection among the three major
      racial/ethnic populations in the United States, we assessed associations between
      67 genetic variants (single nucleotide polymorphisms [SNPs]) among 31 candidate
      genes and serologic evidence of prior HAV infection using a population-based,
      cross-sectional study of 6,779 participants, including 2,619 non-Hispanic whites,
      2,095 non-Hispanic blacks, and 2,065 Mexican Americans enrolled in phase 2 (1991
      1994) of the Third National Health and Nutrition Examination Survey. Among the
      three racial/ethnic groups, the number (weighted frequency) of seropositivity for
      antibody to HAV was 958 (24.9%), 802 (39.2%), and 1540 (71.5%), respectively. No
      significant associations with any of the 67 SNPs were observed among non-Hispanic
      whites or non-Hispanic blacks. In contrast, among Mexican Americans, variants in
      two genes were found to be associated with an increased risk of HAV infection:
      TGFB1 rs1800469 (adjusted odds ratio [OR], 1.38; 95% confidence interval [CI],
      1.14-1.68; P value adjusted for false discovery rate [FDR-P] = 0.017) and XRCC1
      rs1799782 (OR, 1.57; 95% CI, 1.27-1.94; FDR-P = 0.0007). A decreased risk was
      found with ABCB1 rs1045642 (OR, 0.79; 95% CI, 0.71-0.89; FDR-P = 0.0007).
      CONCLUSION: Genetic variants in ABCB1, TGFB1, and XRCC1 appear to be associated
      with susceptibility to HAV infection among Mexican Americans. Replication studies
      involving larger population samples are warranted.

PMID- 22135188
TI  - Long-term outcomes following vocational rehabilitation treatments in patients
      with prolonged fatigue.
AB  - BACKGROUND: Multi-component vocational rehabilitation (VR) provides positive
      short-term outcomes in patients with prolonged fatigue. PURPOSE: The purpose of
      this study is to evaluate the long-term outcomes of Dutch multi-component VR up
      to 18 months after treatment. METHOD: In a pre-post-study, measurements were
      taken before treatment (t0), after treatment (t1) and in long-term follow-ups at
      6 (t2), 12 (t3) and 18 months (t4) after treatment. Primary outcomes (fatigue,
      work participation and workability) and secondary outcomes [physical and social
      functioning, mental health and heart rate variability (HRV)] were assessed over
      time using linear mixed models analyses. Post hoc long-term outcomes were
      compared with t0 and t1. RESULTS: Sixty patients with severe fatigue complaints
      participated. The primary outcomes significantly (p < 0.001) improved at follow
      ups compared with t0 and showed no relapse compared with t1. Moreover, fatigue
      decreased (p < 0.002) whereas workability (p < 0.001) and work participation (p <
      0.001) increased further after treatment (t1). The secondary outcomes, physical
      functioning, mental health, social functioning and HRV, improved significantly (p
      < 0.001, p < 0.001, p < 0.001 and p = 0.049, respectively) over the long term
      compared with t0. At 6-month follow-up (t2), mental health (p < 0.003) and social
      functioning (p = 0.003) further increased after the treatment was stopped.
      CONCLUSION: Multi-component VR treatments seem to significantly and in a
      clinically relevant way decrease fatigue symptoms and improve individual
      functioning and work participation in patients with severe prolonged fatigue over
      the long term and without showing relapse.

PMID- 22135189
TI  - Corolla monosymmetry: evolution of a morphological novelty in the Brassicaceae
      family.
AB  - Evolution of floral monosymmetry is thought to be a major driving force of
      angiosperm radiation, making angiosperms the most successful land plant group in
      terms of species richness. Monosymmetry evolved from a polysymmetric ancestor
      repeatedly in different angiosperm lineages, where it likely facilitated
      diversification through the interaction with insects. Most monosymmetric taxa are
      thus dominated by monosymmetric members. However, in the Brassicaceae, only few
      members develop a monosymmetric corolla with two petal pairs of unequal size,
      making them an ideal system to study the evolution of molecular mechanisms
      enhancing flower complexity. Monosymmetry is controlled by the TCP transcription
      factors that belong to the CYC2 clade in distantly related taxa. In Iberis amara,
      the first crucifer analyzed in terms of monosymmetry development, unequal corolla
      formation is due to a stronger CYC2 clade gene expression in the smaller adaxial
      petals compared with the larger abaxial ones. Phylogenetic reconstruction of the
      crucifer family reveals that the monosymmetric genera Iberis, Calepina, and
      Teesdalia belong to one major crucifer lineage. Monosymmetry is most pronounced
      in Iberis and less so in Calepina and Teesdalia, with a positive dosage-dependent
      correlation between the strength of a CYC2 expression difference and the extent
      of monosymmetry formation. An early adaxial CYC2 expression in floral meristems,
      observed in many distantly related taxa, might have facilitated the repeated
      evolution of CYC2-controlled monosymmetry. Comparison of early and late CYC2
      expression in monosymmetric and polysymmetric crucifers representative for the
      four major crucifer lineages reveals that an adaxial CYC2 expression in floral
      meristems is likely ancestral for the Brassicaceae. However, it got lost in all
      analyzed monosymmetric members and is, as such, not a prerequisite for the
      establishment of corolla monosymmetry in crucifers. Here, monosymmetry evolved
      via a heterochronic CYC2 expression shift from an ancestral early adaxial
      expression in floral meristems to an adaxial CYC2 transcript accumulation later
      in petal development. This study emphasizes the potential of regulatory changes
      in the evolution of morphological novelties, like corolla monosymmetry in the
      Brassicaceae. In combination with a corymboid inflorescence, monosymmetry might
      have served as a key invention driving diversification in the genus Iberis
      comprising more than 20 monosymmetric species.

PMID- 22135190
TI  - Rapid functional divergence of a newly evolved polyubiquitin gene in Drosophila
      and its role in the trade-off between male fecundity and lifespan.
AB  - The cost of reproduction is a pivotal trade-off with various biological processes
      during the evolution of organisms. However, the genes and molecular mechanisms
      underlying the evolution of balancing reproductive capacity and its cost are
      still largely unknown. Here, we present a comprehensive study on the evolution,
      expression, and biological functions of a newly evolved pair of X-linked
      polyubiquitin tandemly duplicated genes, CG32744 and CG11700, of which the
      duplication event occurred in Drosophila melanogaster lineage after the split
      from D. simulans clade. We found that CG32744 retains conserved polyubiquitin
      coding sequences across Drosophila species and is ubiquitously expressed, whereas
      CG11700 has accumulated numerous amino acid changes and shows a male-specific
      expression pattern. Null mutants of CG11700 have a higher male fecundity but
      shorter lifespan, whereas its overexpression decreases male fecundity. In
      contrast, the null mutants of the peptide-conserved CG32744 do not exhibit such
      phenotypes. These results suggest that CG11700 might have experienced
      neofunctionalization and evolved important functions in the trade-off between
      male fecundity and lifespan and that CG32744 likely has retained the ancestral
      function.

PMID- 22135191
TI  - Network-level and population genetics analysis of the insulin/TOR signal
      transduction pathway across human populations.
AB  - Genes and proteins rarely act in isolation, but they rather operate as components
      of complex networks of interacting molecules. Therefore, for understanding their
      evolution, it may be helpful to take into account the interaction networks in
      which they participate. It has been shown that selective constraints acting on
      genes depend on the position that they occupy in the network. Less understood is
      how the impact of local adaptation at the intraspecific level is affected by the
      network structure. Here, we analyzed the patterns of molecular evolution of 67
      genes involved in the insulin/target of rapamycin (TOR) signal transduction
      pathway. This well-characterized pathway plays a key role in fundamental
      processes such as energetic metabolism, growth, reproduction, and aging and is
      involved in metabolic disorders such as obesity, insulin resistance, and
      diabetes. For that purpose, we combined genotype data from worldwide human
      populations with current knowledge of the structure and function of the pathway.
      We identified the footprint of recent positive selection in nine of the studied
      genomic regions. Most of the adaptation signals were observed among Middle East
      and North African, European, and Central South Asian populations. We found that
      positive selection preferentially targets the most central elements in the
      pathway, in contrast to previous observations in the whole human interactome.
      This observation indicates that the impact of positive selection on genes
      involved in the insulin/TOR pathway is affected by the pathway structure.

PMID- 22135192
TI  - Rooting the eukaryotic tree with mitochondrial and bacterial proteins.
AB  - By exploiting the large body of genome data and the considerable progress in
      phylogenetic methodology, recent phylogenomic studies have provided new insights
      into the relationships among major eukaryotic groups. However, confident
      placement of the eukaryotic root remains a major challenge. This is due to the
      large evolutionary distance separating eukaryotes from their closest relatives,
      the Archaea, implying a weak phylogenetic signal and strong long-branch
      attraction artifacts. Here, we apply a new approach to the rooting of the
      eukaryotic tree by using a subset of genomic information with more recent
      evolutionary origin-mitochondrial sequences, whose closest relatives are alpha
      Proteobacteria. For this, we identified and assembled a data set of 42
      mitochondrial proteins (mainly encoded by the nuclear genome) and performed
      Bayesian and maximum likelihood analyses. Taxon sampling includes the recently
      sequenced Thecamonas trahens, a member of the phylogenetically elusive Apusozoa.
      This data set confirms the relationships of several eukaryotic supergroups seen
      before and places the eukaryotic root between the monophyletic "unikonts" and
      "bikonts." We further show that T. trahens branches sister to Opisthokonta with
      significant statistical support and question the bikont/excavate affiliation of
      Malawimonas species. The mitochondrial data set developed here (to be expanded in
      the future) constitutes a unique alternative means in resolving deep eukaryotic
      relationships.

PMID- 22135193
TI  - Measurement of liver iron overload: noninvasive calibration of MRI-R2* by
      magnetic iron detector susceptometer.
AB  - An accurate assessment of body iron accumulation is essential for the diagnosis
      and therapy of iron overload in diseases such as thalassemia or hemochromatosis.
      Magnetic iron detector susceptometry and MRI are noninvasive techniques capable
      of detecting iron overload in the liver. Although the transverse relaxation rate
      measured by MRI can be correlated with the presence of iron, a calibration step
      is needed to obtain the liver iron concentration. Magnetic iron detector provides
      an evaluation of the iron overload in the whole liver. In this article, we
      describe a retrospective observational study comparing magnetic iron detector and
      MRI examinations performed on the same group of 97 patients with transfusional or
      congenital iron overload. A biopsy-free linear calibration to convert the average
      transverse relaxation rate in iron overload (R(2) = 0.72), or in liver iron
      concentration evaluated in wet tissue (R(2) = 0.68), is presented. This article
      also compares liver iron concentrations calculated in dry tissue using MRI and
      the existing biopsy calibration with liver iron concentrations evaluated in wet
      tissue by magnetic iron detector to obtain an estimate of the wet-to-dry
      conversion factor of 6.7 +/- 0.8 (95% confidence level).

PMID- 22135194
TI  - Pharmaceutical Statistics 10th anniversary.

PMID- 22135195
TI  - An effective training system for endoscopic submucosal dissection of gastric
      neoplasm.
AB  - BACKGROUND AND STUDY AIMS: A standard training system for endoscopic submucosal
      dissection (ESD) remains to be established. In this study, we evaluated the
      validity of our training program for gastric ESD. PATIENTS AND METHODS: Four
      trainees performed gastric ESD for a total of 117 lesions in 107 patients (27 to
      30 consecutive lesions per trainee) at a tertiary referral center during 2 years
      in the training program. Trainees, who already had the fundamental skills and
      knowledge needed for ESD, each assisted at 40 gastric ESD procedures, then in 20
      cases applied post-ESD coagulation (PEC) to gastric mucosal defects; they then
      began to perform ESD, starting with gastric antral lesions. Treatment outcomes,
      including mean procedure time, and rates of en bloc resection, en bloc plus R0
      resections, complications, and self-completion, were evaluated, for the initial
      15 and subsequent 12 to 15 cases. RESULTS: Overall rates of en bloc resection and
      en bloc plus R0 resection were as high as 100 % and 96.6 %, respectively.
      Regarding complications, seven cases of delayed hemorrhage (6.0 %) and three
      cases of perforation (2.6 %) occurred; all complications were solved
      endoscopically. The most frequent reason for operator change was lack of
      submucosal dissection skill. The self-completion rate was more than 80 % even in
      the early period, and did not increase for later cases. CONCLUSIONS: Our training
      system enabled novice operators to perform gastric ESD without a decline in
      clinical outcomes. Key features of this training are prior intensive learning and
      actual ESD during the learning period under expert supervision.

PMID- 22135196
TI  - Participation in colorectal cancer screening trials after first-time invitation:
      a systematic review.
AB  - BACKGROUND AND STUDY AIM: Colorectal cancer (CRC) screening is implemented by an
      increasing number of countries. Participation rates of screening programs
      influence the health benefit and cost-effectiveness of the applied method. The
      aim was to systematically review participation rate after first-time invitation
      for CRC screening with fecal occult blood test (FOBT), sigmoidoscopy,
      colonoscopy, and/or computed tomography (CT) colonography. METHODS: A systematic
      literature search was performed prior to October 1 2009. Prospective CRC
      screening studies of unselected populations reporting participation rates were
      included. RESULTS: After meta-analyses, overall participation rates were found to
      be 47 % for FOBT, 42 % for fecal immunologic tests (FITs), 35 % for
      sigmoidoscopy, 41 % for sigmoidoscopy combined with FIT/FOBT, 28 % for
      colonoscopy, and 22 % for CT colonography. Studies comparing screening methods
      showed higher participation rates for less invasive methods. Studies comparing
      invitation methods showed higher participation rates with general practitioner
      involvement, a more personalized recruitment approach, and reduction of barriers
      that discourage participation. CONCLUSIONS: Knowledge of identified factors
      affecting CRC screening participation can be used to improve screening programs.

PMID- 22135199
TI  - Establishment of a pure NOTES procedure using a conventional flexible endoscope.

PMID- 22135201
TI  - Fully covered self-expandable metallic stents with anchor fins: a rose with many
      thorns.

PMID- 22135202
TI  - Use of covered self-expandable metallic stents in post-endoscopic sphincterotomy
      bleeding.

PMID- 22135206
TI  - lambda5-Phospha[7]helicenes: synthesis, properties, and columnar aggregation with
      one-way chirality.

PMID- 22135205
TI  - Screening for distress, the sixth vital sign: examining self-referral in people
      with cancer over a one-year period.
AB  - PURPOSE: Although research has indicated a diagnosis of cancer is most often
      distressing for patients and their families, few studies have examined which
      patients access resources to manage distress or how distress levels affect
      resource utilization. This study explored psychosocial and supportive care
      resource utilization in a large cancer population at a Canadian tertiary cancer
      centre over a 12-month period in a usual care setting. METHODS: Patients who were
      new to the Tom Baker Cancer Centre completed the Distress Thermometer, the Pain
      and Fatigue Thermometers, the Psychological Screen for Cancer (Part C) that
      measures anxiety and depression, self-report questions on resources accessed and
      a demographic form at baseline, 3, 6 and 12 months. No feedback or specific
      triage to services was provided in order to observe usual care practices.
      RESULTS: A total of 714 patients provided baseline data with 505 retained at 12
      months. Twenty-four percent indicated they accessed at least one service (e.g.
      individual counselling, nutritionist or resource social worker) over the 12
      months. Patients who were older, less educated and with lower income were less
      likely to access services. People who reported higher symptom burden were more
      likely to access services at each time point. CONCLUSIONS: Overall levels of
      access of psychosocial services were relatively low in this population and varied
      by socio-demographic variables and symptom burden. Routine monitoring of
      psychosocial, practical and physical concerns is a potential strategy for
      targeting individuals who may require additional information or support in
      accessing available services to manage their concerns.

PMID- 22135207
TI  - M-atrial natriuretic peptide: a novel antihypertensive protein therapy.
AB  - The natriuretic peptides, specifically atrial natriuretic peptide (ANP), are
      increasingly recognized to play a fundamental role in blood pressure (BP)
      regulation. This role in BP regulation reflects the pluripotent cardiorenal
      actions of ANP, which include diuresis, enhancement of renal blood flow and
      glomerular filtration rate, systemic vasodilatation, suppression of aldosterone,
      and inhibition of the sympathetic nervous system. These actions of ANP, in
      addition to recent human studies demonstrating an association of higher plasma
      ANP with lower risk of hypertension, support the development of an ANP-based
      therapy for hypertension. M-ANP is a novel ANP-based peptide that is resistant to
      proteolytic degradation and possesses greater BP-lowering, renal function
      enhancing, and aldosterone-suppressing properties than native ANP. In an animal
      model of hypertension, M-ANP lowers BP via multiple mechanisms, including
      vasodilatation, diuresis, and inhibition of aldosterone. Importantly, M-ANP
      enhances both glomerular filtration rate and renal blood flow despite reductions
      in BP. The pluripotent BP-lowering actions and concomitant enhancement of renal
      function associated with M-ANP are highly attractive characteristics for an
      antihypertensive agent and underscore the therapeutic potential of M-ANP. M-ANP
      currently is heading into clinical testing, which may advance this novel strategy
      for human hypertension.

PMID- 22135208
TI  - The cyclophilin inhibitor alisporivir prevents hepatitis C virus-mediated
      mitochondrial dysfunction.
AB  - Alisporivir (Debio-025) is an analogue of cyclosporine A and represents the
      prototype of a new class of non-immunosuppressive cyclophilin inhibitors. In
      vitro and in vivo studies have shown that alisporivir inhibits hepatitis C virus
      (HCV) replication, and ongoing clinical trials are exploring its therapeutic
      potential in patients with chronic hepatitis C. Recent data suggest that the
      antiviral effect is mediated by inhibition of cyclophilin A, which is an
      essential host factor in the HCV life cycle. However, alisporivir also inhibits
      mitochondrial permeability transition by binding to cyclophilin D. Because HCV is
      known to affect mitochondrial function, we explored the effect of alisporivir on
      HCV protein-mediated mitochondrial dysfunction. Through the use of inducible cell
      lines, which allow to investigate the effects of HCV polyprotein expression
      independent from viral RNA replication and which recapitulate the major
      alterations of mitochondrial bioenergetics observed in infectious cell systems,
      we show that alisporivir prevents HCV protein-mediated decrease of cell
      respiration, collapse of mitochondrial membrane potential, overproduction of
      reactive oxygen species and mitochondrial calcium overload. Strikingly, some of
      the HCV-mediated mitochondrial dysfunctions could even be rescued by alisporivir.
      CONCLUSION: These observations provide new insights into the pathogenesis of HCV
      related liver disease and reveal an additional mechanism of action of alisporivir
      that is likely beneficial in the treatment of chronic hepatitis C.

PMID- 22135209
TI  - Review article: the influence of psychology and human factors on education in
      anesthesiology.
AB  - PURPOSE: We look at the changing nature of medical education in the developed
      world with particular reference to those areas of the new curriculum frameworks
      which have introduced topics from the psychosocial realm. PRINCIPLE FINDINGS:
      Research in the branch of psychology dealing with human factors has developed a
      useful body of working knowledge which applies to other industries where humans
      interact with the complex systems in which they function. Some findings are
      already being applied to facets of anesthesia performance, including situation
      awareness, effective teamwork, countermeasures against active errors and latent
      pathogens, and limitations of human performance. However, existing lessons and
      practices from industrial or military research may not translate directly into
      effective strategies for anesthesiologists. Collaborative studies between
      psychologists and clinicians should continue in order to provide the anesthetic
      curriculum with an effective body of knowledge for each role of the
      anesthesiologist. Although individual anesthesiologists have made important
      contributions in this field, such material has not been formally incorporated
      into the curricula serving anesthesiologists in the developed world. CONCLUSIONS:
      There is a gap between the human factors psychologists now know and the human
      factors anesthesiologists need to know. As that gap closes, anesthesiologists may
      come to think more like human factor psychologists as well as biomedical
      scientists.

PMID- 22135210
TI  - Review article: teaching, learning, and the pursuit of excellence in anesthesia
      education.
AB  - PURPOSE: Excellence in anesthesia education has been advocated to meet the future
      needs and direction of the specialty. The purpose of this article is twofold:
      first, to review the current medical education literature and theory in order to
      inform teaching and learning in anesthesia; and second, to advocate for
      excellence in anesthesia education. SOURCE: This review considers the general
      education, educational psychology, and medical education literature based on a
      search of the MEDLINE and ERIC databases, educational Web sites, and library
      catalogues. PRINCIPAL FINDINGS: Excellent teaching is considered that which
      facilitates and maximizes learning. A conceptual framework of learning as a
      convergence of teacher, learner, assessment, and context is proposed. The
      contribution of each component to learning is examined in order to enable
      anesthesia teachers to choose and adapt the most appropriate educational
      approaches for their particular contexts. The relationship of excellent teaching,
      scholarly teaching, and the scholarship of teaching is explored. Strategies for
      promoting excellence in anesthesia education are suggested. CONCLUSIONS: The call
      for excellence in anesthesia has become an important theme, particularly with
      respect to education. While excellent teaching is a goal to which all anesthesia
      faculty should aspire, scholarly teaching and scholarship in teaching should also
      be promoted in order to advance anesthesia education for the benefit of the
      profession and ultimately for patient care.

PMID- 22135211
TI  - Assessment of a single-operator real-time ultrasound-guided epidural technique in
      a porcine phantom.

PMID- 22135212
TI  - A user's guide to reading the scholarship of anesthesia education.

PMID- 22135213
TI  - Effects of KCNQ channel modulators on the M-type potassium current in primate
      retinal pigment epithelium.
AB  - Recently, we demonstrated the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts
      in monkey retinal pigment epithelium (RPE) and showed that the M-type current in
      RPE cells is blocked by the specific KCNQ channel blocker XE991. Using patch
      clamp electrophysiology, we investigated the pharmacological sensitivity of the M
      type current in isolated monkey RPE cells to elucidate the subunit composition of
      the channel. Most RPE cells exhibited an M-type current with a voltage for half
      maximal activation of approximately -35 mV. The M-type current activation
      followed a double-exponential time course and was essentially complete within 1
      s. The M-type current was inhibited by micromolar concentrations of the
      nonselective KCNQ channel blockers linopirdine and XE991 but was relatively
      insensitive to block by 10 MUM chromanol 293B or 135 mM tetraethylammonium (TEA),
      two KCNQ1 channel blockers. The M-type current was activated by 1) 10 MUM
      retigabine, an opener of all KCNQ channels except KCNQ1, 2) 10 MUM zinc
      pyrithione, which augments all KCNQ channels except KCNQ3, and 3) 50 MUM N
      ethylmaleimide, which activates KCNQ2, KCNQ4, and KCNQ5, but not KCNQ1 or KCNQ3,
      channels. Application of cAMP, which activates KCNQ1 and KCNQ4 channels, had no
      significant effect on the M-type current. Finally, diclofenac, which activates
      KCNQ2/3 and KCNQ4 channels but inhibits KCNQ5 channels, inhibited the M-type
      current in the majority of RPE cells but activated it in others. The results
      indicate that the M-type current in monkey RPE is likely mediated by channels
      encoded by KCNQ4 and KCNQ5 subunits.

PMID- 22135214
TI  - Constitutive expression of a Mg2+-inhibited K+ current and a TRPM7-like current
      in human erythroleukemia cells.
AB  - Whole cell patch-clamp experiments were undertaken to define the basal K(+)
      conductance(s) in human erythroleukemia cells and its contribution to the setting
      of resting membrane potential. Experiments revealed a non-voltage-activated,
      noninactivating K(+) current. The magnitude of the current recorded under whole
      cell conditions was inhibited by an increase in free intracellular Mg(2+)
      concentration. Activation or inactivation of the Mg(2+)-inhibited K(+) current
      (MIP) was paralleled by activation or inactivation of a Mg(2+)-inhibited TRPM7
      like current displaying characteristics indistinguishable from those reported for
      molecularly identified TRPM7 current. The MIP and TRPM7 currents were inhibited
      by 5-lipoxygenase inhibitors. However, inhibition of the MIP current was
      temporally distinct from inhibition of TRPM7 current, allowing for isolation of
      the MIP current. Isolation of the MIP conductance revealed a current reversing
      near the K(+) equilibrium potential, indicative of a highly K(+)-selective
      conductance. Consistent with this finding, coactivation of the nonselective
      cation current TRPM7 and the MIP current following dialysis with nominally Mg(2+)
      free pipette solution resulted in hyperpolarized whole cell reversal potentials,
      consistent with an important role for the MIP current in the setting of a
      negative resting membrane potential. The MIP and TRPM7-like conductances were
      constitutively expressed under in vivo conditions of intracellular Mg(2+), as
      judged by their initial detection and subsequent inactivation following dialysis
      with a pipette solution containing 5 mM free Mg(2+). The MIP current was blocked
      in a voltage-dependent fashion by extracellular Cs(+) and, to a lesser degree, by
      Ba(2+) and was blocked by extracellular La(3+) and 2-aminoethoxydiphenyl borate.
      MIP currents were unaffected by blockers of ATP-sensitive K(+) channels, human
      ether-a-go-go-related gene current, and intermediate-conductance Ca(2+)-activated
      K(+) channels. In addition, the MIP current displayed characteristics distinct
      from conventional inwardly rectifying K(+) channels. A similar current was
      detected in the leukemic cell line CHRF-288-11, consistent with this current
      being more generally expressed in cells of leukemic origin.

PMID- 22135215
TI  - Estradiol attenuates high glucose-induced endothelial nitrotyrosine: role for
      neuronal nitric oxide synthase.
AB  - Hyperglycemia in diabetes causes increased oxidative stress in the vascular
      endothelium with generation of free radicals such as superoxide. Peroxynitrite, a
      highly reactive species generated from superoxide and nitric oxide (NO), induces
      proinflammatory tyrosine nitration of intracellular proteins under such
      conditions. The female sex hormone estrogen appears to exert protective effects
      on the nondiabetic endothelium. However, several studies show reduced vascular
      protection in women with diabetes, suggesting alterations in estrogen signaling
      under high glucose. In this study, we examined the endothelial effects of
      estrogen under increasing glucose levels, focusing on nitrotyrosine and
      peroxynitrite. Human umbilical vein endothelial cells were incubated with normal
      (5.5 mM) or high (15.5 or 30.5 mM) glucose before addition of estradiol (E2, 1 or
      10 nM). Selective NO synthase (NOS) inhibitors were used to determine the role of
      specific NOS isoforms. Addition of E2 significantly reduced high glucose-induced
      increase in peroxynitrite and consequently, nitrotyrosine. The superoxide levels
      were unchanged, suggesting effects on NO generation. Inhibition of neuronal NOS
      (nNOS) reduced high glucose-induced nitrotyrosine, demonstrating a critical role
      for this enzyme. E2 increased nNOS activity under normal glucose while decreasing
      it under high glucose as determined by its phosphorylation status. These data
      show that nNOS contributes to endothelial peroxynitrite and subsequent
      nitrotyrosine generation under high glucose, which can be attenuated by E2
      through nNOS inhibition. The altered regulation of nNOS by E2 under high glucose
      is a potential therapeutic target in women with diabetes.

PMID- 22135216
TI  - Thiopental-induced insulin secretion via activation of IP3-sensitive calcium
      stores in rat pancreatic beta-cells.
AB  - While glucose-stimulated insulin secretion depends on Ca(2+) influx through
      voltage-gated Ca(2+) channels in the cell membrane of the pancreatic beta-cell,
      there is also ample evidence for an important role of intracellular Ca(2+) stores
      in insulin secretion, particularly in relation to drug stimuli. We report here
      that thiopental, a common anesthetic agent, triggers insulin secretion from the
      intact pancreas and primary cultured rat pancreatic beta-cells. We investigated
      the underlying mechanisms by measurements of whole cell K(+) and Ca(2+) currents,
      membrane potential, cytoplasmic Ca(2+) concentration ([Ca(2+)](i)), and membrane
      capacitance. Thiopental-induced insulin secretion was first detected by enzyme
      linked immunoassay, then further assessed by membrane capacitance measurement,
      which revealed kinetics distinct from glucose-induced insulin secretion. The
      thiopental-induced secretion was independent of cell membrane depolarization and
      closure of ATP-sensitive potassium (K(ATP)) channels. However, accompanied by the
      insulin secretion stimulated by thiopental, we recorded a significant
      intracellular [Ca(2+)] increase that was not from Ca(2+) influx across the cell
      membrane, but from intracellular Ca(2+) stores. The thiopental-induced
      [Ca(2+)](i) rise in beta-cells was sensitive to thapsigargin, a blocker of the
      endoplasmic reticulum Ca(2+) pump, as well as to heparin (0.1 mg/ml) and 2
      aminoethoxydiphenyl borate (2-APB; 100 MUM), drugs that inhibit inositol 1,4,5
      trisphosphate (IP(3)) binding to the IP(3) receptor, and to U-73122, a
      phospholipase C inhibitor, but insensitive to ryanodine. Thapsigargin also
      diminished thiopental-induced insulin secretion. Thus, we conclude that
      thiopental-induced insulin secretion is mediated by activation of the
      intracellular IP(3)-sensitive Ca(2+) store.

PMID- 22135217
TI  - Quick diagnosis units versus hospitalization for the diagnosis of potentially
      severe diseases in Spain.
AB  - OBJECTIVES: We describe the functioning of a quick diagnosis unit (QDU) in a
      Spanish public university hospital to ascertain the utility and cost of the model
      compared to conventional hospitalization. DESIGN: Observational study with a
      prospective and retrospective cohort. SETTING: Spanish tertiary public university
      hospital. PATIENTS: Two thousand consecutive patients evaluated between December
      2007 and July 2010 with potentially severe diseases normally requiring
      hospitalization for diagnosis. For comparative purposes, we analyzed a
      randomized, retrospective cohort of 1454 hospitalized patients. MEASUREMENTS:
      Variables measured included source of referral, reason for consultation, time to
      diagnosis and length-of-stay, hospitalizations avoided, Charlson comorbidity
      index, costs, and patient satisfaction using a telephone survey. RESULTS:
      Suspected anemia, cachexia-anorexia syndrome, febrile syndrome, adenopathies
      and/or palpable masses, abdominal pain, diarrhea, and lung abnormalities
      accounted for 88% of QDU patients. The most-frequent diagnoses were cancer
      (26.3%) and iron-deficiency anemia. QDU patients with anemia were significantly
      younger than hospitalized patients with the same diagnosis (P < 0.0001). Other
      parameters were similar between QDU and hospitalized patients. The mean cost of
      treatment was 3153.87 Euros for hospitalization and 702.33 Euros for the QDU.
      Patients expressed a high degree of satisfaction with QDU care. CONCLUSIONS: QDUs
      can manage the diagnosis of patients with potentially severe diseases equally as
      well as traditional hospitalization, and saves costs. QDU patients expressed a
      high degree of satisfaction, with most preferring this model to hospitalization.

PMID- 22135218
TI  - Effects of B1 inhomogeneity correction for three-dimensional variable flip angle
      T1 measurements in hip dGEMRIC at 3 T and 1.5 T.
AB  - Delayed gadolinium-enhanced MRI of cartilage is a technique for studying the
      development of osteoarthritis using quantitative T(1) measurements. Three
      dimensional variable flip angle is a promising method for performing such
      measurements rapidly, by using two successive spoiled gradient echo sequences
      with different excitation pulse flip angles. However, the three-dimensional
      variable flip angle method is very sensitive to inhomogeneities in the
      transmitted B(1) field in vivo. In this study, a method for correcting for such
      inhomogeneities, using an additional B(1) mapping spin-echo sequence, was
      evaluated. Phantom studies concluded that three-dimensional variable flip angle
      with B(1) correction calculates accurate T(1) values also in areas with high B(1)
      deviation. Retrospective analysis of in vivo hip delayed gadolinium-enhanced MRI
      of cartilage data from 40 subjects showed the difference between three
      dimensional variable flip angle with and without B(1) correction to be generally
      two to three times higher at 3 T than at 1.5 T. In conclusion, the B(1)
      variations should always be taken into account, both at 1.5 T and at 3 T.

PMID- 22135219
TI  - Prevalence of primary aldosteronism in patient's cohorts and in population-based
      studies--a review of the current literature.
AB  - There is an ongoing controversy on the prevalence of primary aldosteronism (PA).
      We aimed to update a meta-analysis published in 2008, that compiled studies
      reporting the prevalence of positive ARR screening tests and PA. We therefore
      reviewed original studies published in 2008 or later to examine whether current
      reports provide similar, higher or lower prevalences of elevated ARRs or PA than
      reports included in the original meta-analysis. A systematic review of English
      articles using PubMed was conducted. Search and extraction of articles were
      performed by one review author; the second review author checked all extracted
      data. We identified 11 eligible studies. The updated, weighted mean prevalences
      of elevated ARRs and PA in primary care (prevalence of high ARRs 16.5%;
      prevalence of PA 4.3%) and referred patients (prevalence of high ARRs 19.6%;
      prevalence of PA 9.5%) were only marginally different from the mean values
      obtained in the original meta-analysis. Among the current studies the maximum
      values for the prevalence of elevated ARRs and PA were substantially lower than
      among the older studies. Our results confirm the main conclusions from the
      original meta-analysis. The prevalence of PA increases with the severity of
      hypertension and the inclusion of current study results did not alter the mean
      prevalences of elevated ARRs and PA in primary care and referred patients.
      Additionally, we found that current studies focus increasingly on patients in
      referral centers or special subgroups, while the prevalence of PA in the general
      hypertensive population is yet unknown.

PMID- 22135220
TI  - Deciphering aromatic oligoamide foldamer-DNA interactions.
AB  - Finest selection: Side-chain selective, end-group selective, diastereoselective,
      and RNA- vs. DNA-selective interactions have been revealed between multiturn
      helical aromatic amide foldamers having cationic side chains and G-quadruplex
      aptamers.

PMID- 22135222
TI  - Dealing with stress.

PMID- 22135221
TI  - Between-session practice and therapeutic alliance as predictors of mindfulness
      after mindfulness-based relapse prevention.
AB  - OBJECTIVES: Mindfulness-based treatments have demonstrated efficacy in reducing
      symptoms in clinical populations. Not surprisingly, research suggests increases
      in client mindfulness might be a mechanism of change in these treatments.
      However, little is known about specific factors that lead to increased
      mindfulness. DESIGN: The present study is a secondary analysis of 93 adults in
      outpatient treatment for substance abuse, assessing effects of between-session
      mindfulness practice and therapeutic alliance on levels of mindfulness after an 8
      week Mindfulness-Based Relapse Prevention (MBRP) program. RESULTS: Between
      session practice over the course of the 8 weeks was predictive of mindfulness at
      postcourse, although not at the 2-month or 4-month follow-up assessments. Client
      rated therapeutic alliance was a significant predictor at the 2-month follow-up,
      although not at 4 months. CONCLUSIONS: These findings suggest that between
      session practice and therapeutic alliance might be important factors in the
      initial increases in mindfulness after mindfulness-based treatments, but factors
      supporting longer term mindfulness might shift over time.

PMID- 22135223
TI  - The taboo of cancer: the experiences of cancer disclosure by Iranian patients,
      their family members and physicians.
AB  - OBJECTIVE: The objective of this study is to describe the experiences of cancer
      disclosure by Iranian cancer patients, their family members and physicians.
      METHODS: Twenty cancer patients, ten family members and eight physicians
      participated in this study. Data were collected via semi-structured, in-depth
      interviews and analyzed using qualitative content analysis. RESULTS: Three
      categories were identified: cancer avoidance, a climate of non-disclosure and
      mutual concern. The findings demonstrated that cancer is a taboo subject and the
      word cancer, as well as other indicative terms, was rarely used in daily
      communication. A climate of non-disclosure predominated because patients were the
      last to know their diagnosis, they were unaware of their prognosis, and family
      members and physicians employed strategies to conceal this information. The
      mutual concern of patients, family members and physicians was the main reason
      that cancer was not discussed. CONCLUSION: Cancer is a taboo subject in Iran that
      is maintained and reinforced primarily because of the mutual concern of patients,
      family members and physicians. The first step to address this taboo and inform
      cancer patients of their diagnosis would be to understand and help mitigate the
      individual, family and social consequences of disclosure.

PMID- 22135224
TI  - Enrichment and detection of peptides from biological systems using designed
      periodic mesoporous organosilica microspheres.
AB  - Periodic mesoporous organosilica microspheres (PMOMs) are designed with
      integrated structural features, including a cubic mesostructure, hydrophobic wall
      composition, a uniform pore size of ~3 nm, and a spherical morphology in
      micrometers, all advantageous for size-selective and highly efficient enrichment
      of peptides from mixtures. Consequently, PMOMs can be used to capture peptides in
      a range of complex biological systems. 

PMID- 22135225
TI  - [A comparison of low-chirp- and notched-noise-evoked auditory brainstem
      response].
AB  - BACKGROUND: In order to obtain a low-frequency specific auditory brainstem
      response (ABR) there are less stimuli that plege a satisfying accordance with the
      ABR threshold and the behavioural threshold. This study investigates the so
      called low-chirp-ABR as to predict a low-frequency-amblyacousia and compares it
      to the notched-noise-500 Hz-ABR. MATERIAL AND METHODS: We evaluated behavioural
      and ABR thresholds to a low-chirp respectively a 500 Hz tone presented in notched
      noise masking from 32 patients with a severe hearing loss at low-frequencies and
      28 patients with normal hearing. RESULTS: The average difference +/- single
      standard deviation between low-chirp-ABR and behavioural threshold is 1.53 dB +/-
      7.68 dB in the group of patient with low-frequency hearing loss and 2.55 dB +/-
      5.46 dB in the group of normal hearing. On the contrary the difference between
      notched-noise-500 Hz- and behavioural thereshold averages 2.67 dB +/- 9.29 dB
      (low-frequency hearing loss) respectively 8.82 dB +/- 7.90 dB (normal hearing).
      In order to verify the equivalence between the several methods we did a
      equivalence test that shows that low-chip-ABR and behavioural threshold can be
      considered as equal to obtain a low-frequency threshold. In contrast the
      comparison of notched-noise-500 Hz-ABR and behavioural threshold proves no
      equivalence. CONCLUSION: We detected a significant equivalence between low-chirp
      ABR and pure-tone audiometric. The ABR to a low-chirp stimulus seems to be rather
      precise in contrast to the notched-noise-500 Hz-evoked-ABR in order to diagnose a
      low-frequency-hearing loss.

PMID- 22135226
TI  - The interplay between mutasynthesis and semisynthesis: generation and evaluation
      of an ansamitocin library.

PMID- 22135227
TI  - Motion correction for myocardial T1 mapping using image registration with
      synthetic image estimation.
AB  - Quantification of myocardial T1 relaxation has potential value in the diagnosis
      of both ischemic and nonischemic cardiomyopathies. Image acquisition using the
      modified Look-Locker inversion recovery technique is clinically feasible for T1
      mapping. However, respiratory motion limits its applicability and degrades the
      accuracy of T1 estimation. The robust registration of acquired inversion recovery
      images is particularly challenging due to the large changes in image contrast,
      especially for those images acquired near the signal null point of the inversion
      recovery and other inversion times for which there is little tissue contrast. In
      this article, we propose a novel motion correction algorithm. This approach is
      based on estimating synthetic images presenting contrast changes similar to the
      acquired images. The estimation of synthetic images is formulated as a
      variational energy minimization problem. Validation on a consecutive patient data
      cohort shows that this strategy can perform robust nonrigid registration to align
      inversion recovery images experiencing significant motion and lead to suppression
      of motion induced artifacts in the T1 map.

PMID- 22135228
TI  - DCE and DW MRI in monitoring response to androgen deprivation therapy in patients
      with prostate cancer: a feasibility study.
AB  - Androgen deprivation therapy (ADT) is a key primary treatment for advanced and
      metastatic prostate cancer and is an important neoadjuvant before radiotherapy.
      We evaluated 3.0 T dynamic contrast-enhanced MRI and diffusion-weighted (DW) MRI
      in monitoring ADT response. Twenty-three consecutive patients with prostate
      cancer treated by primary ADT were included. Imaging was performed at baseline
      and 3 months posttreatment with ADT. After 3 months therapy there was a
      significant reduction in all dynamic contrast-enhanced MRI parameters measured in
      tumor regions of interest (K(trans), k(ep), v(p), IAUGC-90); P < 0.001. Areas of
      normal-appearing peripheral zone showed no significant change; P = 0.285-0.879.
      Post-ADT, there was no significant change in apparent diffusion coefficient
      values in tumors, whilst apparent diffusion coefficient values significantly
      decreased in areas of normal-appearing peripheral zone, from 1.786 * 10(-3) mm(2)
      /s to 1.561 * 10(-3) mm(2) /s; P = 0.007. As expected the median Prostate
      Specific Antigen (PSA) significantly reduced from 30 ng/mL to 1.5 ng/mL
      posttreatment, and median prostate volume dropped from 47.6 cm(3) to 24.9 cm(3) ;
      P < 0.001. These results suggest that dynamic contrast-enhanced MRI and diffusion
      weighted MRI offer different information but that both could prove useful
      adjuncts to the anatomical information provided by T2-weighted imaging. dynamic
      contrast-enhanced as a marker of angiogenesis may help demonstrate ADT resistance
      and diffusion-weighted imaging may be more accurate in determining presence of
      tumor cell death versus residual tumor.

PMID- 22135229
TI  - Quality of life and mental health in caregivers of outpatients with advanced
      cancer.
AB  - OBJECTIVE: This study evaluates the quality of life (QOL) and mental health (MH)
      of caregivers of patients with advanced cancer who are receiving ambulatory
      oncology care and associations with patient, caregiver and care-related
      characteristics. METHODS: Patients with advanced gastrointestinal, genitourinary,
      breast, lung or gynaecologic cancer, and their caregivers, were recruited from 24
      medical oncology clinics for a cluster-randomized trial of early palliative care.
      Caregivers completed the Caregiver QOL--Cancer scale and the Medical Outcomes
      Study Short Form, version 2, and a questionnaire including care-related factors
      such as hours/day providing care and change in work situation. Patients completed
      a demographic questionnaire and measures of their QOL and symptom severity.
      Associations of these factors with caregiver QOL and MH were examined using
      linear regression analyses. RESULTS: Of the 191 caregivers, 84% were
      spouses/partners, 90% cohabited with the patient, half were working and 25% had a
      change in work situation since the patient's diagnosis. On multiple regression
      analysis, better caregiver QOL was associated with better caregiver MH and
      patient physical well-being and with not providing care for other dependents.
      Worse caregiver MH was associated with female caregiver sex, worse patient
      emotional well-being, more hours spent caregiving and change in the caregiver's
      work situation. CONCLUSIONS: Caregivers of ambulatory patients with advanced
      cancer may have compromised QOL and MH associated with worse patient physical and
      emotional well-being and with simultaneously caring for others and working
      outside the home. Early palliative care interventions directed at patient
      symptoms and caregiver support may improve QOL in this population.

PMID- 22135230
TI  - Retinoid-regulated FGF8f secretion by osteoblasts bypasses retinoid stimuli to
      mediate granulocytic differentiation of myeloid leukemia cells.
AB  - Signaling from the human hematopoietic stem cell (HSC) niche formed by
      osteoblastic cells regulates hematopoiesis. We previously found that retinoic
      acid receptor alpha (RARalpha), a transcription factor activated by retinoic acid
      (RA), mediates both granulocytic and osteoblastic differentiation. This effect
      depends on decreased phosphorylation of serine 77 of RARalpha (RARalphaS77) by
      the cyclin-dependent kinase-activating kinase (CAK) complex, a key cell-cycle
      regulator. In this article, we report that, by suppressing CAK phosphorylation of
      RARalpha, RA induces FGF8f to mediate osteosarcoma U2OS cell differentiation in
      an autocrine manner. By contrast, paracrine FGF8f secreted into osteoblast
      conditioned medium by U2OS cells transduced with FGF8f or a phosphorylation
      defective RARalphaS77 mutant, RARalphaS77A, bypasses RA stimuli to cross-mediate
      granulocytic differentiation of different types of human leukemic myeloblasts and
      normal primitive hematopoietic CD34(+) cells, possibly through modulating mitogen
      activated protein kinase (MAPK) pathways. Further experiments using recombinant
      human FGF8f (rFGF8f) stimuli, antibody neutralization, and peptide blocking
      showed that paracrine FGF8f is required for mediating terminal leukemic
      myeloblast differentiation. These studies indicate a novel regulatory mechanism
      of granulocytic differentiation instigated by RA from the HSC niche, which links
      loss of CAK phosphorylation of RARalpha with paracrine FGF8f-mediated MAPK
      signaling to mediate leukemic myeloblast differentiation in the absence of RA.
      Therefore, these findings provide a compelling molecular rationale for further
      investigation of paracrine FGF8f regulation, with the intent of devising HSC
      niche-based FGF8f therapeutics for myeloid leukemia, with or without RA
      resistance.

PMID- 22135231
TI  - Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma
      rationale for comprehensive mutation profiling.
AB  - Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) encodes the
      p110alpha subunit of the mitogenic signaling protein phosphoinositide 3-kinase
      (PI3K). PIK3CA mutations in the helical binding domain and the catalytic subunit
      of the protein have been associated with tumorigenesis and treatment resistance
      in various malignancies. Characteristics of patients with PIK3CA-mutant lung
      adenocarcinomas have not been reported. We examined epidermal growth factor
      receptor (EGFR), Kirsten rate sarcoma viral oncogene homolog (KRAS), v-Raf murine
      sarcoma viral oncogene homolog B1 (BRAF), human epidermal growth factor receptor
      2 (HER2), PIK3CA, v-akt murine thymoma vial oncogene homolog 1 (AKT1), v-ras
      neuroblastoma viral oncogene homolog (NRAS), dual specificity mitogen-activated
      protein kinase kinase 1 (MEK1), and anaplastic lymphoma kinase (ALK) in patients
      with adenocarcinoma of the lung to identify driver mutations. Clinical data were
      obtained from the medical records of individuals with mutations in PIK3CA. Twenty
      three of 1,125 (2%, 95% CI: 1-3) patients had a mutation in PIK3CA, 12 in exon 9
      (10 E545K and 2 E542K), and 11 in exon 20 (3 H1047L and 8 H1047R). The patients
      (57% women) had a median age of 66 at diagnosis (range: 34-78). Eight patients
      (35%) were never smokers. Sixteen of 23 (70%, 95% CI: 49-86) had coexisting
      mutations in other oncogenes-10 KRAS, 1 MEK1, 1 BRAF, 1 ALK rearrangement, and 3
      EGFR exon 19 deletions. We conclude that PIK3CA mutations occur in lung
      adenocarcinomas, usually concurrently with EGFR, KRAS, and ALK. The impact of
      PIK3CA mutations on the efficacy of targeted therapies such as erlotinib and
      crizotinib is unknown. Given the high frequency of overlapping mutations,
      comprehensive genotyping should be carried out on tumor specimens from patients
      enrolling in clinical trials of PI3K and other targeted therapies.

PMID- 22135232
TI  - Evaluation of the antitumor effects and mechanisms of PF00299804, a pan-HER
      inhibitor, alone or in combination with chemotherapy or targeted agents in
      gastric cancer.
AB  - Recently, HER2-directed treatment, such as trastuzumab, has shown clinical
      benefit in HER2-amplified gastric cancer. On the basis of recent studies about
      epidermal growth factor receptor (EGFR) or HER2-targeting agents (including
      gefitinib, lapatinib, and trastuzumab) in gastric cancer, the potent effects of
      pan-HER inhibitors targeting the HER family are anticipated. In this study, we
      evaluated the activity and mechanisms of PF00299804, an irreversible pan-HER
      inhibitor, in gastric cancer in vitro and in vivo models. PF00299804 showed
      significant growth-inhibitory effects in HER2-amplified gastric cancer cells
      (SNU216, N87), and it had lower 50% inhibitory concentration values compared with
      other EGFR tyrosine kinase inhibitors, including gefitinib, lapatinib, BIBW-2992,
      and CI-1033. PF00299804 induced apoptosis and G(1) arrest and inhibited
      phosphorylation of receptors in the HER family and downstream signaling pathways
      including STAT3, AKT, and extracellular signal-regulated kinases (ERK) in HER2
      amplified gastric cancer cells. PF00299804 also blocked EGFR/HER2, HER2/HER3, and
      HER3/HER4 heterodimer formation as well as the association of HER3 with p85alpha
      in SNU216 cells. The combination of PF00299804 with clinically relevant
      chemotherapeutic agents or molecular-targeted agents including trastuzumab (an
      anti-HER2 monoclonal antibody), CP751871 (an IGF1R inhibitor), PD0325901 (an
      ERK1/2 inhibitor), and PF04691502 (a PI3K/mTOR inhibitor) produced synergistic
      effects. These findings indicate that PF00299804 can be used as a targeted
      therapy for the treatment of HER2-amplified gastric cancer through inhibition of
      HER family heterodimer formation and may augment antitumor efficacy of
      chemotherapeutic and/or molecular-targeted agents.

PMID- 22135233
TI  - Alkylboronic esters from copper-catalyzed borylation of primary and secondary
      alkyl halides and pseudohalides.
AB  - Easy access: An unprecedented copper-catalyzed cross-coupling reaction of the
      title compounds with diboron reagents is described (see scheme; Ts = 4
      toluenesulfonyl). This reaction can be used to prepare both primary and secondary
      alkylboronic esters having diverse structures and functional groups. The
      resulting products would be difficult to access by other means.

PMID- 22135234
TI  - Improving GRAPPA using cross-sampled autocalibration data.
AB  - In conventional generalized autocalibrating partially parallel acquisitions, the
      autocalibration signal (ACS) lines are acquired with a frequency-encoding
      direction in parallel to other undersampled lines. In this study, a cross
      sampling method is proposed to acquire the ACS lines orthogonal to the
      undersampled lines. This cross sampling method increases the amount of
      calibration data along the direction, where k-space is undersampled, and
      especially improves the calibration accuracy when a small number of ACS lines are
      acquired. The cross sampling method is implemented with swapped frequency and
      phase encoding gradients. In addition, an iterative coregistration method is also
      developed to correct the inconsistency between the ACS and undersampled data,
      which are acquired separately in two orthogonal directions. The same calibration
      and reconstruction procedure as conventional generalized autocalibrating
      partially parallel acquisitions is then applied to the corrected data to recover
      the unacquired k-space data and obtain the final image. Reconstruction results
      from simulations, phantom and in vivo human brain experiments have distinctly
      demonstrated that the proposed method, named cross-sampled generalized
      autocalibrating partially parallel acquisitions, can effectively reduce the
      aliasing artifacts of conventional generalized autocalibrating partially parallel
      acquisitions when very few ACS lines are acquired, especially at high outer k
      space reduction factors.

PMID- 22135236
TI  - Striking alkenol versus allenol reactivity: metal-catalyzed chemodifferentiating
      oxycyclization of enallenols.
AB  - An efficient chemodivergent metal-controlled methodology for the generation of
      different highly functionalized oxygen heterocycles from common enallenol
      substrates has been developed. Chemoselectivity control in the O-C
      functionalization of an enallenol can be achieved through the choice of catalyst:
      AuCl(3), PdCl(2), and [PtCl(2)(CH(2)=CH(2))](2) exclusively afford dihydrofurans
      through selective activation of the allenol moiety, whereas FeCl(3) solely gives
      tetrahydrofurans or tetrahydropyrans through selective activation of the alkenol
      moiety. We have also shown that a combination of metal-mediated hydroalkoxylation
      and allenic aminocyclization reactions can lead to a useful preparation of the
      tetrahydrofuro[3,2-b]piperidine core of the antimalarial alkaloid isofebrifugine.
      These divergent heterocyclization reactions have been developed experimentally
      and additionally, their mechanisms have been investigated by a theoretical study.

PMID- 22135235
TI  - Control of mitochondrial activity by miRNAs.
AB  - Mitochondria supply energy for physiological function and they participate in the
      regulation of other cellular events including apoptosis, calcium homeostasis, and
      production of reactive oxygen species. Thus, mitochondria play a critical role in
      the cells. However, dysfunction of mitochondria is related to a variety of
      pathological processes and diseases. MicroRNAs (miRNAs) are a class of small
      noncoding RNAs about 22 nucleotides long, and they can bind to the 3'
      untranslated region (3'-UTR) of mRNAs, thereby inhibiting mRNA translation or
      promoting mRNA degradation. We summarize the molecular regulation of
      mitochondrial metabolism, structure, and function by miRNAs. Modulation of miRNAs
      levels may provide a new therapeutic approach for the treatment of mitochondria
      related diseases.

PMID- 22135237
TI  - Spectroscopic evidence for the unusual stereochemical configuration of an
      endosome-specific lipid.
AB  - At a glance: The stereochemical configuration of the diglycerophosphate backbone
      of the endosome-specific lipid bis(monoacylglycero)phosphate (BMP, see picture)
      was determined by (1)H NMR spectroscopy. Enantiomeric discrimination was
      facilitated by introduction of D-camphor ketals as chiral shift reagents, and
      enantiopure synthetic BMP analogues were prepared as reference materials. Natural
      BMP exhibited the unusual sn-1,1' diglycerophosphate backbone.

PMID- 22135238
TI  - Mapping of (3) He apparent diffusion coefficient anisotropy at sub-millisecond
      diffusion times in an elastase-instilled rat model of emphysema.
AB  - Hyperpolarized (3) He gas can provide detailed anatomical maps of the macroscopic
      airways in the lungs (i.e., ventilation) as well as insight into the lung
      microstructure through the apparent diffusion coefficient. In particular, the
      apparent diffusion coefficient of (3) He in the lung exhibits anisotropic effects
      that depend on diffusion time (delta), and it has been shown to be
      extraordinarily sensitive to enlargement in terminal airways and alveoli
      associated with emphysema. In this study, the anisotropic nature of the (3) He
      apparent diffusion coefficient is studied in a rat model of emphysema, based on
      elastase instillation, specifically for delta values less than one millisecond.
      Longitudinal (D(L) ) and transverse (D(T) ) diffusion coefficients were mapped at
      delta = 360 MUs and delta = 800 MUs based on a cylinder model of lung structure
      and correlated with histological measurement of alveolar damage based on mean
      linear intercept (L(m) ). Whole-lung mean D(T) measured at delta = 360 MUs in the
      elastase-instilled rat lungs (0.14 +/- 0.09 cm(2) /s) demonstrated the most
      significant increase (p = 0.00195) compared to the sham-instilled cohort (0.06 +/
      0.06 cm(2) /s) and had a strong linear correlation with L(m) (Pearson's
      correlation coefficient of 0.9). These results suggest that measurement of (3) He
      apparent diffusion coefficient anisotropy, specifically D(T) , can provide a
      sensitive indicator of emphysema, particularly at very short diffusion times
      (delta = 360 MUs).

PMID- 22135239
TI  - Leptin regulates estrogen receptor gene expression in ATDC5 cells through the
      extracellular signal regulated kinase signaling pathway.
AB  - Both estrogen and leptin play an important role in the regulation of
      physiological processes of endochondral bone formation in linear growth. Estrogen
      receptors (ERalpha and ERbeta) are known as members of the superfamily of nuclear
      steroid hormone receptors and are detected in all zones of growth plate
      chondrocytes. They can be regulated in a ligand-independent manner. Whether
      leptin regulates ERs in the growth plate is still not clear. To explore this
      issue, chondrogenic ATDC5 cells were used in the present study. Messenger RNA and
      protein analyses were performed by quantitative PCR and Western blotting. We
      found that both ERalpha and ERbeta were dynamically expressed during the ATDC5
      cell differentiation for 21 days. Leptin (50 ng/ml) significantly upregulated
      ERalpha and ERbeta mRNA and protein levels 48 h after leptin stimulation (P<0.05)
      at day 14. The up-regulation of ERalpha and ERbeta mRNA by leptin was shown in a
      dose-dependent manner, but the most effective dose of leptin was different (100
      and 1,000 ng/ml, respectively). Furthermore, we confirmed that leptin augmented
      the phosphorylation of ERK1/2 in a time-dependent manner. A maximum eightfold
      change was observed at 15 min. Finally, a specific ERK1/2 inhibitor, UO126,
      blocked leptin-induced ERs regulation in ATDC5 cells, indicating that ERK1/2
      mediates, partly, the effects of leptin on ERs. These data demonstrate, for the
      first time, that leptin regulates the expression of ERs in growth plate
      chondrocytes via ERK signaling pathway, thereby suggesting a crosstalk between
      leptin and estrogen receptors in the regulation of bone formation.

PMID- 22135240
TI  - A follow-up study on men tested for BRCA1/BRCA2 mutations: impacts and coping
      processes.
AB  - OBJECTIVE: The objective of this study was to examine cognitive, emotional, and
      behavioral impacts of testing for germline mutations in breast/ovarian cancer
      associated genes (BRCA1/BRCA2) among men who undergo genetic testing. METHODS: A
      cross-sectional study compared 51 mutation carriers with 30 men who tested
      negative for the mutations in both genes. Telephone interviews were conducted
      with all participants at a median of 4 years after disclosure of test results in
      a genetic counseling context. Testing-related distress, cancer risk perceptions,
      perceived behavioral changes following testing, and perceptions of breast cancer
      were measured using standard questionnaires. RESULTS: Up to 4 years postgenetic
      testing, 48% of those who tested positively report that the test increased their
      perceptions of risk, and 74% of them increased surveillance for cancer. Men who
      had been tested as non-carriers did not report increased perceived risk (0%) and
      relatively few increased surveillance (31%). Carriers were significantly more
      distressed from testing, perceived breast cancer as having less consequences and
      emotional effects on the patient, and as being more treatable than non-carriers.
      CONCLUSIONS: These results have implications with regard to the Self Regulatory
      Theory. They show that (i) illness representations are affected by fear-arousing
      health information; (ii) risk perceptions elicit health behaviors; and (iii) men
      tested for BRCA mutations have specific concerns that should be attended to.

PMID- 22135241
TI  - Rare-earth metal allyl and hydrido complexes supported by an (NNNN)-type
      macrocyclic ligand: synthesis, structure, and reactivity toward biomass-derived
      furanics.
AB  - The preparation and characterization of a series of neutral rare-earth metal
      complexes [Ln(Me(3)TACD)(eta(3)-C(3)H(5))(2)] (Ln=Y, La, Ce, Pr, Nd, Sm)
      supported by the 1,4,7-trimethyl-1,4,7,10-tetraazacyclododecane anion (Me(3)TACD(
      )) are reported. Upon treatment of the neutral allyl complexes
      [Ln(Me(3)TACD)(eta(3)-C(3)H(5))(2)] with Bronsted acids, monocationic allyl
      complexes [Ln(Me(3)TACD)(eta(3)-C(3)H(5))(thf)(2)][B(C(6)X(5))(4)] (Ln=La, Ce,
      Nd, X=H, F) were isolated and characterized. Hydrogenolysis gave the hydride
      complexes [Ln(Me(3)TACD)H(2)](n) (Ln=Y, n=3; La, n=4; Sm). X-ray crystallography
      showed the lanthanum hydride to be tetranuclear. Reactivity studies of
      [Ln(Me(3)TACD)R(2)](n) (R=eta(3)-C(3)H(5), n=0; R=H, n=3,4) towards furan
      derivatives includes hydrosilylation and deoxygenation under ring-opening
      conditions.

PMID- 22135242
TI  - Integrated active tracking detector for MRI-guided interventions.
AB  - We present a fully integrated detector suitable for active tracking of
      interventional devices in MR-guided interventions. The single-chip microsystem
      consists of a detection coil, a tuning capacitor, an intermediate frequency
      downconversion receiver, and a phase-locked-loop-based frequency synthesizer.
      Thanks to the integrated mixer, the chip output stage delivers an analog
      frequency-downconverted NMR signal in the frequency range from 0 to 200 kHz. The
      microchip, realized in a standard complementary metal oxide semiconductor
      technology, has a size of 1 * 2 * 0.74 mm(3) and operates at a frequency of 63
      MHz (i.e., in 1.5 T clinical scanners). Tests in a standard clinical scanner
      demonstrate the compatibility of the complementary metal oxide semiconductor
      microchip with clinical MRI systems. Using a solid sample of cis-polyisoprene
      having a size of 1 * 1.9 * 0.8 mm(3) as internal signal source, the detector
      achieves a three-dimensional isotropic spatial resolution of 0.15 mm in a
      measuring time of 100 ms.

PMID- 22135243
TI  - The role of somatostatin and dopamine D2 receptors in endocrine tumors.
AB  - Somatostatin (SS) and dopamine (DA) receptors have been highlighted as two
      critical regulators in the negative control of hormonal secretion in a wide group
      of human endocrine tumors. Both families of receptors belong to the superfamily
      of G protein-coupled receptors and share a number of structural and functional
      characteristics. Because of the generally reported high expression of
      somatostatin receptors (SSTRs) in neuroendocrine tumors (NET), somatostatin
      analogs (SSA) have a pronounced role in the medical therapy for this class of
      tumors, especially pituitary adenomas and well-differentiated
      gastroenteropancreatic NET (GEP NET). Moreover, NET express not only SSTR but
      also frequently dopamine receptors (DRs), and DA agonists targeting the D(2)
      receptor (D(2)) have been demonstrated to be effective in controlling hormone
      secretion and cell proliferation in in vivo and in vitro studies. The treatment
      with SSAs combined with DA agonists has already been demonstrated efficacious in
      a subgroup of patients with GH-secreting pituitary adenomas and few reported
      cases of carcinoids. The recent availability of new selective and universal SSA
      and DA agonists, as well as the chimeric SS/DA compounds, may shed new light on
      the potential role of SSTR and D(2) as combined targets for biotherapy in NET.
      This review provides an overview of the latest studies evaluating the expression
      of SSTR and DR in NET, focusing on their co-expression and the possible clinical
      implications of such co-expression. Moreover, the most recent insights in SSTR
      and D(2) pathophysiology and the future perspectives for treatment with SSA, DA
      agonists, and SS/DA chimeric compounds are discussed.

PMID- 22135244
TI  - Intramolecular domino electrophilic and thermal cyclization of peri-ethynylene
      naphthalene oligomers.
AB  - The intramolecular electrophilic or thermal cyclization of arylene ethynylene
      precursors recently became a powerful method for the synthesis of new polycyclic
      aromatic hydrocarbons (PAHs). In this work, we investigated in detail the
      synthesis and intramolecular cyclization reaction of a series of peri-ethynylene
      naphthalene oligomers in which the ethynylene units are fixed in close proximity
      within the naphthalene framework. The high reactivity of these precursors led to
      simultaneous thermal cyclization reactions, even during their syntheses.
      Electrophilic cyclizations with iodine were also undertaken. Several new PAHs
      containing five-membered rings, for example, indeno[2,1-a]phenalene,
      acenaphtho[1,2-a]pyrene, and benzo- or naphtho-annulated fluoranthene
      derivatives, were synthesized and their structures were unambiguously determined
      by X-ray crystallographic analysis. Plausible mechanisms were proposed and it was
      demonstrated that oligomers most probably underwent intramolecular domino
      cyclization via either radical or cationic intermediates. The photophysical and
      electrochemical properties of these new PAHs were investigated and some of them
      displayed amphoteric redox behavior, due to the existence of five-membered rings.

PMID- 22135245
TI  - Interobserver reproducibility of quantitative meniscus analysis using coronal
      multiplanar DESS and IWTSE MR imaging.
AB  - The objective of this study was to determine the interobserver reproducibility of
      quantitative measures of meniscus size and position, and to compare the
      interobserver reproducibility and agreement between a double echo steady state
      water excitation and an intermediately-weighted turbo spin-echo sequence. Eight
      knees (four healthy, four with radiographic knee osteoarthritis) from the
      Osteoarthritis Initiative cohort were studied. Manual segmentation of the menisci
      was performed by three observers and quantitative measures of meniscus size and
      position (i.e., extrusion) computed using image analysis software. The root mean
      square interobserver reproducibility error (e.g., 5.4% for medial meniscus volume
      with double echo steady state and 8.4% with intermediately-weighted turbo spin
      echo) was found considerably smaller than the intersubject variability (average
      ratio ~1:3). The lowest interobserver reproducibility error for meniscus
      extrusion was obtained for the central five coronal slices across the tibial
      surface. Quantitative meniscus measures from double echo steady state and
      intermediately-weighted turbo spin-echo were highly correlated (r = 0.71 to 0.99
      for the medial meniscus).

PMID- 22135246
TI  - Specific recognition of beta-cyclodextrin by a tetraphenylethene luminogen
      through a cooperative boronic acid/diol interaction.

PMID- 22135247
TI  - A perylene diimide rotaxane: synthesis, structure and electrochemically driven de
      threading.
AB  - The first example of a [2]-rotaxane in which a perylene diimide acts as a
      recognition site has been synthesised and characterised. The interlocked nature
      of the compound has been verified by both NMR studies and an X-ray structure
      determination. Electrochemical investigations confirm that the nature of the
      redox processes associated with the perylene diimide are modified by the
      complexation process and that it is possible to mono-reduce the [2]-rotaxane to
      give a radical anion based rotaxane. Further reduction of the compound leads to
      de-threading of the macrocycle from the reduced PTCDI recognition site. Our
      synthetic strategies confirm the potential of PTCDI-based rotaxanes as viable
      targets for the preparation of complex interlocked species.

PMID- 22135248
TI  - Extracranial measurements of amide proton transfer using exchange-modulated point
      resolved spectroscopy (EXPRESS).
AB  - Chemical exchange saturation transfer (CEST) imaging has been used experimentally
      in a large range of applications. However, full quantification of CEST effects in
      vivo using standard imaging sequences is time consuming as a large number of
      saturation frequency offsets, each followed by an imaging readout, are required
      to define a z spectrum. Furthermore, outside the brain, the presence of fat can
      confound the interpretation of z spectra. A novel acquisition and post-processing
      technique is presented in this study, named exchange-modulated point-resolved
      spectroscopy (EXPRESS), which aims to address these limitations and to enable
      spatially localised, high signal-to-noise measurements of CEST effects in vivo.
      Using amide proton exchange (APT) measurements in tumours, it is demonstrated
      that the acquisition of two-dimensional EXPRESS spectra composed of chemical
      shift and saturation frequency offset dimensions allows the correction of CEST
      data containing both fat and water signals, which is a common confounding
      property of tissues found outside the brain.

PMID- 22135249
TI  - Recycling of 3He from lung magnetic resonance imaging.
AB  - We have developed the means to recycle (3) He exhaled by patients after imaging
      the lungs using magnetic resonance of hyperpolarized (3) He. The exhaled gas is
      collected in a helium leak proof bag and further compressed into a steel bottle.
      The collected gas contains about 1-2% of (3) He, depending on the amount
      administered and the number of breaths collected to wash out the (3) He gas from
      the lungs. (3) He is separated from the exhaled air using zeolite molecular sieve
      adsorbent at 77 K followed by a cold head at 8 K. Residual gaseous impurities are
      finally absorbed by a commercial nonevaporative getter. The recycled (3) He gas
      features high purity, which is required for repolarization by metastability
      exchange optical pumping. At present, we achieve a collection efficiency of 80
      84% for exhaled gas from healthy volunteers and cryogenic separation efficiency
      of 95%.

PMID- 22135250
TI  - Prosthetic joint infection caused by Helcococcus kunzii.
AB  - Helcococcus kunzii was isolated by sonication and conventional cultures obtained
      from a case of infection following total knee prosthesis in an immunocompetent
      patient. The patient recovered uneventfully. This is the first known case of an
      H. kunzii prosthetic joint infection.

PMID- 22135251
TI  - High frequency of Tropheryma whipplei in culture-negative endocarditis.
AB  - "Classical" Whipple's disease (cWD) is caused by Tropheryma whipplei and is
      characterized by arthropathy, weight loss, and diarrhea. T. whipplei infectious
      endocarditis (TWIE) is rarely reported, either in the context of cWD or as
      isolated TWIE without signs of systemic infection. The frequency of TWIE is
      unknown, and systematic studies are lacking. Here, we performed an observational
      cohort study on the incidence of T. whipplei infection in explanted heart valves
      in two German university centers. Cardiac valves from 1,135 patients were
      analyzed for bacterial infection using conventional culture techniques, PCR
      amplification of the bacterial 16S rRNA gene, and subsequent sequencing. T.
      whipplei-positive heart valves were confirmed by specific PCR, fluorescence in
      situ hybridization, immunohistochemistry, histological examination, and culture
      for T. whipplei. Bacterial endocarditis was diagnosed in 255 patients, with
      streptococci, staphylococci, and enterococci being the main pathogens. T.
      whipplei was the fourth most frequent pathogen, found in 16 (6.3%) cases, and
      clearly outnumbered Bartonella quintana, Coxiella burnetii, and members of the
      HACEK group (Haemophilus species, Actinobacillus actinomycetemcomitans,
      Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae). In this
      cohort, T. whipplei was the most commonly found pathogen associated with culture
      negative infective endocarditis.

PMID- 22135252
TI  - Is vancomycin MIC "creep" method dependent? Analysis of methicillin-resistant
      Staphylococcus aureus susceptibility trends in blood isolates from North East
      Scotland from 2006 to 2010.
AB  - This study investigated "creep" in vancomycin and daptomycin MICs among
      methicillin-resistant Staphylococcus aureus (MRSA) isolates from blood cultures
      over a 5-year period in a hospital in the United Kingdom, using different
      susceptibility testing methods. Trends in vancomycin and daptomycin
      susceptibility were evaluated by using Etest performed prospectively on isolates
      in routine clinical practice from December 2007 to December 2010 (n = 102).
      Comparison was made to results from prospective testing of subcultures at the
      Scottish MRSA Reference Laboratory, using an automated system (Vitek 2) and
      retrospective testing (Etest and CLSI reference broth microdilution [BMD] method)
      of stored isolates from 2006 to 2010 (n = 208). Spearman's rank correlations
      revealed a significant increase in vancomycin MIC (P = 0.012) and a significant
      decrease in daptomycin MIC (P = 0.03) by year of study for Etest results from the
      time of isolation. However, neither trend was replicated in MICs from automated
      or retrospective testing. The Friedman test revealed a significant difference
      between vancomycin MICs obtained from the same samples by different testing
      methods (chi(2) [3 degrees of freedom] = 97; P < 0.001). MICs from automated
      testing and Etest analysis of stored isolates were significantly lower than those
      from Etest analysis at the time of isolation for both antibiotics (P < 0.001).
      Effects of storage on the MIC appeared within the first 6 months of storage.
      Inconsistent evidence on vancomycin MIC creep and the relevance of the MIC to
      clinical outcome may arise from differences in susceptibility testing methods,
      including storage of isolates. There is a need to standardize and streamline
      susceptibility testing of vancomycin against MRSA.

PMID- 22135253
TI  - Preparation and evaluation of recombinant severe fever with thrombocytopenia
      syndrome virus nucleocapsid protein for detection of total antibodies in human
      and animal sera by double-antigen sandwich enzyme-linked immunosorbent assay.
AB  - The recent emergence of the human infection confirmed to be caused by severe
      fever with thrombocytopenia syndrome virus (SFTSV) in China is of global concern.
      Safe diagnostic immunoreagents for determination of human and animal
      seroprevalence in epidemiological investigations are urgently needed. This paper
      describes the cloning and expression of the nucleocapsid (N) protein of SFTSV. An
      N-protein-based double-antigen sandwich enzyme-linked immunosorbent assay (ELISA)
      system was set up to detect the total antibodies in human and animal sera. We
      reasoned that as the double-antigen sandwich ELISA detected total antibodies with
      a higher sensitivity than traditional indirect ELISA, it could be used to detect
      SFTSV-specific antibodies from different animal species. The serum neutralization
      test was used to validate the performance of this ELISA system. All human and
      animal sera that tested positive in the neutralization test were also positive in
      the sandwich ELISA, and there was a high correlation between serum neutralizing
      titers and ELISA readings. Cross-reactivity was evaluated, and the system was
      found to be highly specific to SFTSV; all hantavirus- and dengue virus-confirmed
      patient samples were negative. SFTSV-confirmed human and animal sera from both
      Anhui and Hubei Provinces in China reacted with N protein in this ELISA,
      suggesting no major antigenic variation between geographically disparate virus
      isolates and the suitability of this assay in nationwide application. ELISA
      results showed that 3.6% of the human serum samples and 47.7% of the animal field
      serum samples were positive for SFTSV antibodies, indicating that SFTSV has
      circulated widely in China. This assay, which is simple to operate, poses no
      biohazard risk, does not require sophisticated equipment, and can be used in
      disease surveillance programs, particularly in the screening of large numbers of
      samples from various animal species.

PMID- 22135254
TI  - Detection of human papillomavirus type 18 E7 oncoprotein in cervical smears: a
      feasibility study.
AB  - Persistent infections by high-risk human papillomaviruses (HPVs) are the main
      etiological factor for cervical cancer, and expression of HPV E7 oncoproteins was
      suggested to be a potential marker for tumor progression. The objective of this
      study was to generate new reagents for the detection of the HPV18 E7 oncoprotein
      in cervical smears. Rabbit monoclonal antibodies against recombinant E7 protein
      of HPV type 18 (HPV18) were generated and characterized using Western blotting,
      epitope mapping, indirect immunofluorescence, and immunohistochemistry. One clone
      specifically recognizing HPV18 E7 was used for the development of a sandwich
      enzyme-linked immunosorbent assay (ELISA). The assay was validated using
      recombinant E7 proteins of various HPV types and lysates from E7-positive
      cervical carcinoma cells. A total of 14 HPV18 DNA-positive cervical swab
      specimens and 24 HPV DNA-negative-control specimens were used for the
      determination of E7 protein levels by the newly established sandwich ELISA. On
      the basis of the average absorbance values obtained from all 24 negative
      controls, a cutoff above which a clinical sample can be judged E7 positive was
      established. Significant E7 signals 6- to 30-fold over background were found in 7
      out of 14 abnormal HPV18 DNA-positive cervical smear specimens. This feasibility
      study demonstrates for the first time that HPV18 E7 oncoprotein can be detected
      in cervical smears.

PMID- 22135255
TI  - Diagnosis of tuberculosis by trained African giant pouched rats and confounding
      impact of pathogens and microflora of the respiratory tract.
AB  - Trained African giant-pouched rats (Cricetomys gambianus) can detect
      Mycobacterium tuberculosis and show potential for the diagnosis of tuberculosis
      (TB). However, rats' ability to discriminate between clinical sputum containing
      other Mycobacterium spp. and nonmycobacterial species of the respiratory tract is
      unknown. It is also unknown whether nonmycobacterial species produce odor similar
      to M. tuberculosis and thereby cause the detection of smear-negative sputum.
      Sputum samples from 289 subjects were analyzed by smear microscopy, culture, and
      rats. Mycobacterium spp. were isolated on Lowenstein-Jensen medium, and
      nonmycobacterial species were isolated on four different media. The odor from
      nonmycobacterial species from smear- and M. tuberculosis culture-negative sputa
      detected by >=2 rats ("rat positive") was analyzed by gas chromatography-mass
      spectrometry and compared to the M. tuberculosis odor. Rats detected 45 of 56
      confirmed cases of TB, 4 of 5 suspected cases of TB, and 63 of 228 TB-negative
      subjects (sensitivity, 80.4%; specificity, 72.4%; accuracy, 73.9%; positive
      predictive value, 41.7%; negative predictive value, 93.8%). A total of 37 (78.7%)
      of 47 mycobacterial isolates were M. tuberculosis complex, with 75.7% from rat
      positive sputa. Ten isolates were nontuberculous mycobacteria, one was M.
      intracellulare, one was M. avium subsp. hominissuis, and eight were unidentified.
      Rat-positive sputa with Moraxella catarrhalis, Streptococcus pneumoniae,
      Staphylococcus spp., and Enterococcus spp. were associated with TB. Rhodococcus,
      Nocardia, Streptomyces, Staphylococcus, and Candida spp. from rat-positive sputa
      did not produce M. tuberculosis-specific volatiles (methyl nicotinate, methyl
      para-anisate, and ortho-phenylanisole). Prevalence of Mycobacterium-related
      Nocardia and Rhodococcus in smear-negative sputa did not equal that of smear
      negative mycobacteria (44.7%), of which 28.6% were rat positive. These findings
      and the absence of M. tuberculosis-specific volatiles in nonmycobacterial species
      indicate that rats can be trained to specifically detect M. tuberculosis.

PMID- 22135256
TI  - Characterization of ertapenem-resistant Enterobacter cloacae in a Taiwanese
      university hospital.
AB  - The emergence of carbapenem resistance in Enterobacteriaceae has become a great
      concern. The aim of this study was to characterize ertapenem-resistant
      Enterobacter cloacae isolates from a Taiwanese university hospital. A total of
      355 nonduplicated E. cloacae isolates collected in 2007 were analyzed by
      antimicrobial susceptibility testing with and without an inhibitor of efflux
      pumps and AmpC beta-lactamase. The phenotype of extended-spectrum beta-lactamase
      (ESBL), profile of outer membrane proteins (OMPs), and clonal relatedness were
      investigated by the double-disk synergy test, urea/SDS-PAGE, and pulsed-field gel
      electrophoresis (PFGE), respectively. beta-Lactamase genes were examined by PCR
      and sequencing, and the expression of efflux pump gene acrB was evaluated by
      reverse transcription-PCR. The contribution of porin deficiency to resistance was
      investigated by restoring functional porin genes on plasmids. We demonstrated
      that ertapenem resistance was prevalent (53/355; 14.9%) in E. cloacae. Among the
      strains, IMP-8, SHV-12, and TEM-1 beta-lactamases were identified in 3 (5.7%), 40
      (75.5%), and 46 (86.8%) isolates, respectively. PFGE showed clonal diversity
      among these isolates. Phenotypes of ESBL, AmpC beta-lactamase overproduction, an
      active efflux pump, and change in the expression of OMPs were found in 18 (34%),
      11 (20.8%), 51 (96.2%), and 23 (43.4%) of ertapenem-resistant strains,
      respectively. Ertapenem MICs were restored in strains with OmpC and OmpF
      expression plasmids. This study suggests that ESBL, AmpC beta-lactamase
      overproduction, and decreased OMP expression combined with an active efflux pump
      contribute to the ertapenem resistance of E. cloacae. The presence of IMP-8 may
      also play a partial role in ertapenem resistance in Taiwan.

PMID- 22135257
TI  - Liquid-based urine cytology as a tool for detection of human papillomavirus,
      Mycoplasma spp., and Ureaplasma spp. in men.
AB  - Liquid-based urine cytology (LB-URC) was evaluated for cytological diagnosis and
      detection of human papillomavirus (HPV), Mycoplasma, and Ureaplasma. Midstream
      urine samples were collected from 141 male patients with urethritis and 154
      controls without urethritis, and sediment cells were preserved in liquid-based
      cytology solution. Urethral swabs from urethritis patients were tested for the
      presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Papanicolaou tests
      were performed for cytological evaluation. HPV, Mycoplasma, and Ureaplasma
      genomes were determined by PCR-based methods, and localization of HPV DNA in
      urothelial cells was examined by in situ hybridization (ISH). The beta-globin
      gene was positive in 97.9% of LB-URC samples from urethritis patients and in
      97.4% of control samples, suggesting that high-quality cellular DNA was obtained
      from the LB-URC samples. HPV DNA was detected in 29 (21.0%) urethritis cases and
      in five (3.3%) controls (P < 0.05). HPV type 16 (HPV 16) was most commonly found
      in urethritis patients. Cytological evaluations could be performed for 92.1% of
      urethritis patients and 64.3% of controls. Morphological changes suggestive of
      HPV infection were seen in 20.7% of the HPV-positive samples, and ISH
      demonstrated the presence of HPV DNA in both squamous and urothelial cells in HPV
      positive samples. Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum,
      and Ureaplasma urealyticum were detected in 14.5%, 10.9%, 6.5%, and 12.3% of
      urethritis patients, respectively. The prevalence rates of these microorganisms
      (except Ureaplasma parvum) were significantly higher in urethritis cases than
      controls (P < 0.05). LB-URC is applicable for detection of HPV, Mycoplasma, and
      Ureaplasma. HPV infection occurs in urothelial cells, especially in gonococcal
      urethritis.

PMID- 22135258
TI  - Evaluation of the VersaTREK system compared to the Bactec MGIT 960 system for
      first-line drug susceptibility testing of Mycobacterium tuberculosis.
AB  - The aim of this study was to evaluate the reliability of the VersaTREK system for
      Mycobacterium tuberculosis drug susceptibility testing compared with results
      obtained with the Bactec MGIT 960 system. A total of 67 strains were evaluated.
      Overall agreement was at 98.5%. Kappa indexes were 1.0 for isoniazid, rifampin,
      and ethambutol, 0.937 for pyrazinamide, and 0.907 for streptomycin. The VersaTREK
      system is validated for M. tuberculosis drug susceptibility testing.

PMID- 22135259
TI  - Direct analysis and identification of pathogenic Lichtheimia species by matrix
      assisted laser desorption ionization-time of flight analyzer-mediated mass
      spectrometry.
AB  - Zygomycetes of the order Mucorales can cause life-threatening infections in
      humans. These mucormycoses are emerging and associated with a rapid tissue
      destruction and high mortality. The resistance of Mucorales to antimycotic
      substances varies between and within clinically important genera such as Mucor,
      Rhizopus, and Lichtheimia. Thus, an accurate diagnosis before onset of
      antimycotic therapy is recommended. Matrix-assisted laser desorption ionization
      (MALDI)-time of flight (TOF) mass spectrometry (MS) is a potentially powerful
      tool to rapidly identify infectious agents on the species level. We investigated
      the potential of MALDI-TOF MS to differentiate Lichtheimia species, one of the
      most important agents of mucormycoses. Using the Bruker Daltonics FlexAnalysis
      (version 3.0) software package, a spectral database library with m/z ratios of
      2,000 to 20,000 Da was created for 19 type and reference strains of clinically
      relevant Zygomycetes of the order Mucorales (12 species in 7 genera). The
      database was tested for accuracy by use of 34 clinical and environmental isolates
      of Lichtheimia comprising a total of five species. Our data demonstrate that
      MALDI-TOF MS can be used to clearly discriminate Lichtheimia species from other
      pathogenic species of the Mucorales. Furthermore, the method is suitable to
      discriminate species within the genus. The reliability and robustness of the
      MALDI-TOF-based identification are evidenced by high score values (above 2.3) for
      the designation to a certain species and by moderate score values (below 2.0) for
      the discrimination between clinically relevant (Lichtheimia corymbifera, L.
      ramosa, and L. ornata) and irrelevant (L. hyalospora and L. sphaerocystis)
      species. In total, all 34 strains were unequivocally identified by MALDI-TOF MS
      with score values of >1.8 down to the generic level, 32 out of 34 of the
      Lichtheimia isolates (except CNM-CM 5399 and FSU 10566) were identified
      accurately with score values of >2 (probable species identification), and 25 of
      34 isolates were identified to the species level with score values of >2.3
      (highly probable species identification). The MALDI-TOF MS-based method reported
      here was found to be reproducible and accurate, with low consumable costs and
      minimal preparation time.

PMID- 22135260
TI  - Life-threatening respiratory tract disease with human bocavirus-1 infection in a
      4-year-old child.
AB  - The disease spectrum associated with human bocavirus-1 infection remains to be
      fully defined. We report a case of bocavirus-1-associated bronchiolitis, leading
      to severe respiratory failure and extracorporeal membrane oxygenation in a 4-year
      old child, and suggest blood testing for human bocavirus-1 in children with
      severe respiratory tract infection.

PMID- 22135261
TI  - Genotypic and phenotypic characterization of carriage and invasive disease
      isolates of Neisseria meningitidis in Finland.
AB  - The relationship between carriage and the development of invasive meningococcal
      disease is not fully understood. We investigated the changes in meningococcal
      carriage in 892 military recruits in Finland during a nonepidemic period (July
      2004 to January 2006) and characterized all of the oropharyngeal meningococcal
      isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and
      genotypic (porA typing and multilocus sequence typing) methods. For comparison,
      84 invasive meningococcal disease strains isolated in Finland between January
      2004 and February 2006 were also analyzed. The rate of meningococcal carriage was
      significantly higher at the end of military service than on arrival (18% versus
      2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates
      belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates
      belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged
      to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23
      clonal complex were cultured more often from oropharyngeal samples taken during
      the acute phase of respiratory infection than from samples taken at health
      examinations at the beginning and end of military service (odds ratio [OR], 6.7;
      95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was
      associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the
      ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to
      35.2). These findings point to the importance of meningococcal vaccination for
      military recruits and also to the need for an efficacious vaccine against
      serogroup B isolates.

PMID- 22135262
TI  - Baseline cellular HIV DNA load predicts HIV DNA decline and residual HIV plasma
      levels during effective antiretroviral therapy.
AB  - Cellular human immunodeficiency virus type 1 (HIV-1) DNA may be considered a
      marker of disease progression with significant predictive power, but published
      data on its correlation with plasma HIV RNA levels and CD4 counts in acute and
      chronic patients are not conclusive. We evaluated a cohort of 180 patients naive
      for antiretroviral therapy before the beginning of treatment and after a
      virological response in order to define the indicators correlated with HIV DNA
      load decrease until undetectability. The following variables were evaluated as
      continuous variables: age, CD4 cell count and log(10) HIV DNA level at baseline
      and follow-up, and baseline log(10) HIV RNA level. Primary HIV infection at the
      start of therapy, an HIV RNA level at follow-up of <2.5 copies/ml, origin,
      gender, and transmission risk were evaluated as binary variables. The decline of
      HIV DNA values during effective therapy was directly related to baseline HIV DNA
      and HIV RNA values, to an increase in the number of CD4 cells, and to the
      achievement of an HIV RNA load of <2.5 copies/ml. An undetectable cellular HIV
      DNA load was achieved by 21.6% of patients at the follow-up time point and
      correlated significantly with lower baseline cellular HIV DNA values and with
      being in the primary stage of infection when therapy started. In conclusion,
      early treatment facilitated the achievement of undetectable levels of plasma
      viremia and cellular HIV DNA and a better recovery of CD4 lymphocytes. HIV DNA
      levels before and during highly active antiretroviral therapy may be used as a
      new tool for monitoring treatment efficacy.

PMID- 22135264
TI  - Quality, frailty, and common sense.

PMID- 22135263
TI  - Complete genome and clinicopathological characterization of a virulent Newcastle
      disease virus isolate from South America.
AB  - Newcastle disease (ND) is one of the most important diseases of poultry,
      negatively affecting poultry production worldwide. The disease is caused by
      Newcastle disease virus (NDV) or avian paramyxovirus type 1 (APMV-1), a negative
      sense single-stranded RNA virus of the genus Avulavirus, family Paramyxoviridae.
      Although all NDV isolates characterized to date belong to a single serotype of
      APMV-1, significant genetic diversity has been described between different NDV
      isolates. Here we present the complete genome sequence and the
      clinicopathological characterization of a virulent Newcastle disease virus
      isolate (NDV-Peru/08) obtained from poultry during an outbreak of ND in Peru in
      2008. Phylogenetic reconstruction and analysis of the evolutionary distances
      between NDV-Peru/08 and other isolates representing established NDV genotypes
      revealed the existence of large genomic and amino differences that clearly
      distinguish this isolate from viruses of typical NDV genotypes. Although NDV
      Peru/08 is a genetically distinct virus, pathogenesis studies conducted with
      chickens revealed that NDV-Peru/08 infection results in clinical signs
      characteristic of velogenic viscerotropic NDV strains. Additionally, vaccination
      studies have shown that an inactivated NDV-LaSota/46 vaccine conferred full
      protection from NDV-Peru/08-induced clinical disease and mortality. This
      represents the first complete characterization of a virulent NDV isolate from
      South America.

PMID- 22135265
TI  - The negative U wave in the setting of demand ischemia (AUGUST 2011).

PMID- 22135266
TI  - Dabigatran (OCTOBER 2011).

PMID- 22135268
TI  - A 25-year-old man with very high alkaline phosphatase.

PMID- 22135269
TI  - A less common source of dyspnea in scleroderma.

PMID- 22135270
TI  - Presumed premature ventricular contractions.

PMID- 22135271
TI  - A 54-year-old woman with pancytopenia.

PMID- 22135272
TI  - Essential tremor: choosing the right management plan for your patient.
AB  - Essential tremor is a common neurologic problem seen widely at all levels of
      patient care. It should be differentiated from secondary causes of tremor and
      Parkinson disease. It can be managed with commonly used drugs. However, severe,
      resistant, or atypical cases should be referred to a specialist for evaluation
      and the possible use of botulinum toxin or deep brain stimulation.

PMID- 22135273
TI  - Bioidentical hormone therapy: clarifying the misconceptions.
AB  - Many women are turning to bioidentical hormone therapy on the basis of
      misconceptions and unfounded claims, eg, that this therapy can reverse the aging
      process and that it is more natural and safe than approved hormone therapy. The
      aim of this article is to clarify some of the misconceptions.

PMID- 22135274
TI  - Heart failure in frail, older patients: we can do 'MORE'.
AB  - A comprehensive approach is necessary in managing heart failure in frail older
      adults. To provide optimal care, physicians need to draw on knowledge from the
      fields of internal medicine, geriatrics, and cardiology. The acronym "MORE" is a
      mnemonic for what heart failure management should include: multidisciplinary
      care, attention to other (ie, comorbid) diseases, restrictions (of salt, fluid,
      and alcohol), and discussion of end-of-life issues.

PMID- 22135275
TI  - Structural complex of sterol 14alpha-demethylase (CYP51) with 14alpha
      methylenecyclopropyl-Delta7-24, 25-dihydrolanosterol.
AB  - Sterol 14alpha-demethylase (CYP51) that catalyzes the removal of the 14alpha
      methyl group from the sterol nucleus is an essential enzyme in sterol
      biosynthesis, a primary target for clinical and agricultural antifungal azoles
      and an emerging target for antitrypanosomal chemotherapy. Here, we present the
      crystal structure of Trypanosoma (T) brucei CYP51 in complex with the substrate
      analog 14alpha-methylenecyclopropyl-Delta7-24,25-dihydrolanosterol (MCP). This
      sterol binds tightly to all protozoan CYP51s and acts as a competitive inhibitor
      of F105-containing (plant-like) T. brucei and Leishmania (L) infantum orthologs,
      but it has a much stronger, mechanism-based inhibitory effect on I105-containing
      (animal/fungi-like) T. cruzi CYP51. Depicting substrate orientation in the
      conserved CYP51 binding cavity, the complex specifies the roles of the contact
      amino acid residues and sheds new light on CYP51 substrate specificity. It also
      provides an explanation for the effect of MCP on T. cruzi CYP51. Comparison with
      the ligand-free and azole-bound structures supports the notion of structural
      rigidity as the characteristic feature of the CYP51 substrate binding cavity,
      confirming the enzyme as an excellent candidate for structure-directed design of
      new drugs, including mechanism-based substrate analog inhibitors.

PMID- 22135276
TI  - Comprehensive sequence analysis of nine Usher syndrome genes in the UK National
      Collaborative Usher Study.
AB  - BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder comprising
      retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It
      is clinically and genetically heterogeneous with three distinctive clinical types
      (I-III) and nine Usher genes identified. This study is a comprehensive clinical
      and genetic analysis of 172 Usher patients and evaluates the contribution of
      digenic inheritance. METHODS: The genes MYO7A, USH1C, CDH23, PCDH15, USH1G,
      USH2A, GPR98, WHRN, CLRN1 and the candidate gene SLC4A7 were sequenced in 172 UK
      Usher patients, regardless of clinical type. RESULTS: No subject had definite
      mutations (nonsense, frameshift or consensus splice site mutations) in two
      different USH genes. Novel missense variants were classified UV1-4 (unclassified
      variant): UV4 is 'probably pathogenic', based on control frequency <0.23%,
      identification in trans to a pathogenic/probably pathogenic mutation and
      segregation with USH in only one family; and UV3 ('likely pathogenic') as above,
      but no information on phase. Overall 79% of identified pathogenic/UV4/UV3
      variants were truncating and 21% were missense changes. MYO7A accounted for
      53.2%, and USH1C for 14.9% of USH1 families (USH1C:c.496+1G>A being the most
      common USH1 mutation in the cohort). USH2A was responsible for 79.3% of USH2
      families and GPR98 for only 6.6%. No mutations were found in USH1G, WHRN or
      SLC4A7. CONCLUSIONS: One or two pathogenic/likely pathogenic variants were
      identified in 86% of cases. No convincing cases of digenic inheritance were
      found. It is concluded that digenic inheritance does not make a significant
      contribution to Usher syndrome; the observation of multiple variants in different
      genes is likely to reflect polymorphic variation, rather than digenic effects.

PMID- 22135278
TI  - Rehabilitation, weaning and physical therapy strategies in chronic critically ill
      patients.
AB  - In critically ill patients, a prolonged hospital stay, due to the initial acute
      insult and adverse side-effects of drug therapy, may cause severe late
      complications, such as muscle weakness, prolonged symptoms, mood alterations and
      poor health-related quality of life. The clinical aims of physical rehabilitation
      in both medical and surgical intensive care units (ICUs) are focussed on the
      patient to improve their short- and even long-term care. The purpose of this
      article is to review the currently available evidence on comprehensive
      rehabilitation programmes in critically ill patients, and describe the key
      components and techniques used, particularly in specialised ICUs. Despite the
      literature suggesting that several techniques have led to beneficial effects and
      that muscle training is associated with weaning success, scientific evidence is
      limited. Due to limitations in undertaking comparative studies in ICUs, further
      studies with solid clinical short- and long-term outcome measures are now
      welcomed.

PMID- 22135277
TI  - Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations
      of COPD: MAESTRAL results.
AB  - Bacterial infections causing acute exacerbations of chronic obstructive pulmonary
      disease (AECOPD) frequently require antibacterial treatment. More evidence is
      needed to guide antibiotic choice. The Moxifloxacin in Acute Exacerbations of
      Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind
      non-inferiority outpatient study. Patients were aged >= 60 yrs, with an
      Anthonisen type I exacerbation, a forced expiratory volume in 1 s < 60% predicted
      and two or more exacerbations in the last year. Following stratification by
      steroid use patients received moxifloxacin 400 mg p.o. q.d. (5 days) or
      amoxicillin/clavulanic acid 875/125 mg p.o. b.i.d. (7 days). The primary end
      point was clinical failure 8 weeks post-therapy in the per protocol population.
      Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end
      point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95%
      CI -5.89-3.83%). In patients with confirmed bacterial AECOPD, moxifloxacin led to
      significantly lower clinical failure rates than amoxicillin/clavulanic acid (in
      the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out
      of 335, respectively; p=0.016). Confirmed bacterial eradication at end of therapy
      was associated with higher clinical cure rates at 8 weeks post-therapy overall
      (p=0.0014) and for moxifloxacin (p=0.003). Patients treated with oral
      corticosteroids had more severe disease and higher failure rates. The MAESTRAL
      study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in
      the treatment of outpatients with AECOPD. Both therapies were well tolerated.

PMID- 22135279
TI  - Nocturnal hypoxaemia and hypercapnia in children with neuromuscular disorders.
AB  - The aim of the study was to identify daytime predictors of nocturnal gas exchange
      anomalies in children with neuromuscular disease (NMD) and normal daytime gas
      exchange. Lung function tests, respiratory muscle evaluation and nocturnal gas
      exchange were obtained as part of routine evaluation. We included 52 consecutive
      children with Duchenne muscular dystrophy (n = 20), spinal muscular atrophy (n =
      10) and other NMD (n = 22). 20 patients had nocturnal hypoxaemia, defined as
      minimal arterial oxygen saturation measured by pulse oximetry (S(p,O(2))) <90%
      for >= 2% of night time, and 22 had nocturnal hypercapnia, defined as maximal
      transcutaneous carbon dioxide tension (P(tc,CO(2))) >50 mmHg for >= 2% of night
      time. Forced vital capacity and helium functional residual capacity correlated
      with minimal nocturnal S(p,O(2)) (p = 0.009 and p = 0.01, respectively). Daytime
      pH correlated negatively with maximal nocturnal P(tc,CO(2)) (p=0.005) and daytime
      arterial carbon dioxide tension (P(a,CO(2))) correlated with the percentage of
      time with a P(tc,CO(2)) >50 mmHg (p = 0.02). Sniff nasal inspiratory pressure
      correlated with minimal nocturnal S(p,O(2)) (p = 0.02). Daytime P(a,CO(2)) was a
      weak predictor of nocturnal hypercapnia (sensitivity 80%; specificity 57%).
      Daytime lung function and respiratory muscle parameters correlate poorly with
      nocturnal hypoxaemia and hypercapnia in children with NMD and normal daytime gas
      exchange, which necessitates more systematic sleep studies in these children.

PMID- 22135280
TI  - Effect of pulmonary exacerbations on long-term lung function decline in cystic
      fibrosis.
AB  - It is unknown what proportion of long-term lung function decline in cystic
      fibrosis (CF) is explained by pulmonary exacerbations. The aim of this study was
      to determine how exacerbations requiring hospitalisation contribute to the course
      of CF lung disease. This was a retrospective cohort study. The primary outcome
      was the rate of decline of forced expiratory volume in 1 s (FEV(1)) % predicted.
      Out of 851 subjects, 415 (48.8%) subjects had >= 1 exacerbation. After adjustment
      for confounders, the annual rate of FEV(1) decline in those without an
      exacerbation was 1.2% per yr (95% CI 1.0-1.5), compared with 2.5% per yr (95% CI
      2.1-2.8) in those with an exacerbation. The proportion of overall FEV(1) decline
      associated with >= 1 exacerbation was 52% (95% CI 35.0-68.9). For a given number
      of exacerbations, the annual rate of FEV(1) decline was greatest in subjects with
      <= 6 months between exacerbations. Half of FEV(1) decline seen in CF patients was
      associated with pulmonary exacerbations. Time between exacerbations, specifically
      <= 6 months between exacerbations, plays an important contribution to overall
      lung function decline. These findings support using time to next exacerbation as
      a clinical end-point for CF trials.

PMID- 22135281
TI  - Prognosis of acute respiratory distress syndrome in neutropenic cancer patients.
AB  - To date, no study has been specifically designed to identify determinants of
      death in neutropenic cancer patients presenting with acute respiratory distress
      syndrome (ARDS). The aim of this study was to identify early predictive factors
      of 28-day mortality in these patients. Factors associated with 28-day mortality
      during intensive care unit (ICU) stay were also described. 70 consecutive cancer
      patients with ARDS and neutropenia were prospectively analysed over a 6-yr
      period. Mortality at 28 days was 63%. Factors independently associated with good
      prognosis were: lobar ARDS (OR 0.10, 95% CI 0.02-0.48), use of initial antibiotic
      treatment active on difficult to treat bacteria (ticarcillin-resistant
      Pseudomonas aeruginosa, Stenotrophomonas maltophilia or extended-spectrum beta
      lactamase-producing strains) (OR 0.08, 95% CI 0.02-0.33) and first-line
      chemotherapy (OR 0.08, 95% CI 0.02-0.37). During the ICU stay, mortality was
      associated with the markers of organ dysfunctions, the absence of neutropenia
      recovery and the use of vasopressors. During the first 3 weeks, the conditional
      probability of discharge alive from ICU did not decrease. At ICU admission, first
      line chemotherapy, lobar ARDS and antibiotic treatment active on difficult-to
      treat bacteria were associated with survival. During ICU stay, mortality was
      associated with organ dysfunctions and use of vasopressors. Most survivors have
      an ICU stay of >3 weeks.

PMID- 22135282
TI  - Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary
      fibrosis.
AB  - The aim of this study was to evaluate the risk factors for and outcomes of acute
      exacerbations in patients with advanced idiopathic pulmonary fibrosis (IPF), and
      to examine the relationship between disease severity and neovascularisation in
      explanted IPF lung tissue. 55 IPF patients assessed for lung transplantation were
      divided into acute (n=27) and non-acute exacerbation (n=28) groups. Haemodynamic
      data was collected at baseline, at the time of acute exacerbation and at lung
      transplantation. Histological analysis and CD31 immunostaining to quantify
      microvessel density (MVD) was performed on the explanted lung tissue of 13
      transplanted patients. Acute exacerbations were associated with increased
      mortality (p=0.0015). Pulmonary hypertension (PH) at baseline and acute
      exacerbations were associated with poor survival (p<0.01). PH at baseline was
      associated with a significant risk of acute exacerbations (HR 2.217, p=0.041).
      Neovascularisation (MVD) was significantly increased in areas of cellular
      fibrosis and significantly decreased in areas of honeycombing. There was a
      significant inverse correlation between mean pulmonary artery pressure and MVD in
      areas of honeycombing. Acute exacerbations were associated with significantly
      increased mortality in patients with advanced IPF. PH was associated with the
      subsequent development of an acute exacerbation and with poor survival.
      Neovascularisation was significantly decreased in areas of honeycombing, and was
      significantly inversely correlated with mean pulmonary arterial pressure in areas
      of honeycombing.

PMID- 22135283
TI  - Population-based survival for malignant mesothelioma after introduction of novel
      chemotherapy.
AB  - Malignant mesothelioma is known for its dismal prognosis and poor response to
      conventional treatment. Chemotherapy with cisplatin-antifolate combinations
      recently showed promising response rates and prolonged survival in randomised
      trials. To assess the impact of this development on clinical practice and
      survival at a population-based level, treatment patterns and survival trends were
      studied for patients diagnosed with mesothelioma in the period 1995-2006. 4,731
      records were retrieved from the Netherlands Cancer Registry and chemotherapy use
      and median survival were analysed. For the periods 1995-1998 to 2005-2006,
      chemotherapy use increased from 8% to 36%. Median survival increased over time
      from 7.1 months to 9.2 months. For pleural mesothelioma, multivariable analysis
      demonstrated that survival was poorer for elderly patients and sarcomatoid
      tumours. The prognostic impact of chemotherapy increased with time. Median
      survival for chemotherapy treated patients improved from 10.1 months (1995-1998)
      to 13.1 months (2005-2006). For peritoneal mesothelioma, median survival was poor
      (3.9 months) but better for females and younger patients. This study demonstrates
      that chemotherapy use increased at a national level and coincided with an
      improvement in survival. The novel chemotherapy regimen appears to be more
      effective but, due to the observational nature of this study, alternative
      explanations cannot be excluded.

PMID- 22135284
TI  - Effectiveness of exercise training in patients with COPD: the role of muscle
      fatigue.
AB  - The improvement in exercise performance in response to exercise training varies
      greatly from one patient with chronic obstructive pulmonary disease to another.
      It is possible that in a portion of patients the muscle stimulus applied during
      exercise training is insufficient to elicit training effects. We investigated
      whether patients presenting quadriceps contractile fatigue after training have
      more favourable effects of a rehabilitation programme. 46 patients followed a 3
      month high-intensity exercise training programme. Exercise capacity, quadriceps
      force and quality of life were measured before and after the programme. Exercise
      training-induced quadriceps contractile fatigue was assessed after 1 month of
      rehabilitation with magnetic stimulation. A fall in quadriceps force of >=15%, 15
      min after training was considered as significant fatigue. 29 (63%) out of 46
      patients developed significant fatigue. Patients with fatigue had a higher
      increase in 6-min walk distance (median (interquartile range) 57 (47-103) m
      versus 17 (-7-46) m; p=0.0023) and Chronic Respiratory Disease Questionnaire
      score (mean+/-sd 22+/-12 points versus 14+/-12 points; p=0.028) after the
      training programme compared with patients without fatigue. Improvements in
      quadriceps force and maximal exercise capacity were similar in both subgroups.
      Patients who develop quadriceps contractile fatigue during exercise training show
      greater training effects in terms of functional exercise capacity and health
      related quality of life.

PMID- 22135285
TI  - Solution structure of the dimerization domain of the eukaryotic stalk P1/P2
      complex reveals the structural organization of eukaryotic stalk complex.
AB  - The lateral ribosomal stalk is responsible for the kingdom-specific binding of
      translation factors and activation of GTP hydrolysis during protein synthesis.
      The eukaryotic stalk is composed of three acidic ribosomal proteins P0, P1 and
      P2. P0 binds two copies of P1/P2 hetero-dimers to form a pentameric P-complex.
      The structure of the eukaryotic stalk is currently not known. To provide a better
      understanding on the structural organization of eukaryotic stalk, we have
      determined the solution structure of the N-terminal dimerization domain (NTD) of
      P1/P2 hetero-dimer. Helix-1, -2 and -4 from each of the NTD-P1 and NTD-P2 form
      the dimeric interface that buries 2200 A(2) of solvent accessible surface area.
      In contrast to the symmetric P2 homo-dimer, P1/P2 hetero-dimer is asymmetric.
      Three conserved hydrophobic residues on the surface of NTD-P1 are replaced by
      charged residues in NTD-P2. Moreover, NTD-P1 has an extra turn in helix-1, which
      forms extensive intermolecular interactions with helix-1 and -4 of NTD-P2.
      Truncation of this extra turn of P1 abolished the formation of P1/P2 hetero
      dimer. Systematic truncation studies suggest that P0 contains two spine-helices
      that each binds one copy of P1/P2 hetero-dimer. Modeling studies suggest that a
      large hydrophobic cavity, which can accommodate the loop between the spine
      helices of P0, can be found on NTD-P1 but not on NTD-P2 when the helix-4 adopts
      an 'open' conformation. Based on the asymmetric properties of NTD-P1/NTD-P2, a
      structural model of the eukaryotic P-complex with P2/P1:P1/P2 topology is
      proposed.

PMID- 22135286
TI  - Promiscuous DNA synthesis by human DNA polymerase theta.
AB  - The biological role of human DNA polymerase theta (POLQ) is not yet clearly
      defined, but it has been proposed to participate in several cellular processes
      based on its translesion synthesis capabilities. POLQ is a low-fidelity
      polymerase capable of efficient bypass of blocking lesions such as abasic sites
      and thymine glycols as well as extension of mismatched primer termini. Here, we
      show that POLQ possesses a DNA polymerase activity that appears to be template
      independent and allows efficient extension of single-stranded DNA as well as
      duplex DNA with either protruding or multiply mismatched 3'-OH termini. We
      hypothesize that this DNA synthesis activity is related to the proposed role for
      POLQ in the repair or tolerance of double-strand breaks.

PMID- 22135288
TI  - Dr.VIS: a database of human disease-related viral integration sites.
AB  - Viral integration plays an important role in the development of malignant
      diseases. Viruses differ in preferred integration site and flanking sequence.
      Viral integration sites (VIS) have been found next to oncogenes and common
      fragile sites. Understanding the typical DNA features near VIS is useful for the
      identification of potential oncogenes, prediction of malignant disease
      development and assessing the probability of malignant transformation in gene
      therapy. Therefore, we have built a database of human disease-related VIS
      (Dr.VIS, http://www.scbit.org/dbmi/drvis) to collect and maintain human disease
      related VIS data, including characteristics of the malignant disease, chromosome
      region, genomic position and viral-host junction sequence. The current build of
      Dr.VIS covers about 600 natural VIS of 5 oncogenic viruses representing 11
      diseases. Among them, about 200 VIS have viral-host junction sequence.

PMID- 22135287
TI  - miRNEST database: an integrative approach in microRNA search and annotation.
AB  - Despite accumulating data on animal and plant microRNAs and their functions,
      existing public miRNA resources usually collect miRNAs from a very limited number
      of species. A lot of microRNAs, including those from model organisms, remain
      undiscovered. As a result there is a continuous need to search for new microRNAs.
      We present miRNEST (http://mirnest.amu.edu.pl), a comprehensive database of
      animal, plant and virus microRNAs. The core part of the database is built from
      our miRNA predictions conducted on Expressed Sequence Tags of 225 animal and 202
      plant species. The miRNA search was performed based on sequence similarity and as
      many as 10,004 miRNA candidates in 221 animal and 199 plant species were
      discovered. Out of them only 299 have already been deposited in miRBase.
      Additionally, miRNEST has been integrated with external miRNA data from
      literature and 13 databases, which includes miRNA sequences, small RNA sequencing
      data, expression, polymorphisms and targets data as well as links to external
      miRNA resources, whenever applicable. All this makes miRNEST a considerable miRNA
      resource in a sense of number of species (544) that integrates a scattered miRNA
      data into a uniform format with a user-friendly web interface.

PMID- 22135289
TI  - MMDB: 3D structures and macromolecular interactions.
AB  - Close to 60% of protein sequences tracked in comprehensive databases can be
      mapped to a known three-dimensional (3D) structure by standard sequence
      similarity searches. Potentially, a great deal can be learned about proteins or
      protein families of interest from considering 3D structure, and to this day 3D
      structure data may remain an underutilized resource. Here we present enhancements
      in the Molecular Modeling Database (MMDB) and its data presentation, specifically
      pertaining to biologically relevant complexes and molecular interactions. MMDB is
      tightly integrated with NCBI's Entrez search and retrieval system, and mirrors
      the contents of the Protein Data Bank. It links protein 3D structure data with
      sequence data, sequence classification resources and PubChem, a repository of
      small-molecule chemical structures and their biological activities, facilitating
      access to 3D structure data not only for structural biologists, but also for
      molecular biologists and chemists. MMDB provides a complete set of detailed and
      pre-computed structural alignments obtained with the VAST algorithm, and provides
      visualization tools for 3D structure and structure/sequence alignment via the
      molecular graphics viewer Cn3D. MMDB can be accessed at
      http://www.ncbi.nlm.nih.gov/structure.

PMID- 22135290
TI  - PoSSuM: a database of similar protein-ligand binding and putative pockets.
AB  - Numerous potential ligand-binding sites are available today, along with hundreds
      of thousands of known binding sites observed in the PDB. Exhaustive similarity
      search for such vastly numerous binding site pairs is useful to predict protein
      functions and to enable rapid screening of target proteins for drug design.
      Existing databases of ligand-binding sites offer databases of limited scale. For
      example, SitesBase covers only ~33,000 known binding sites. Inferring protein
      function and drug discovery purposes, however, demands a much more comprehensive
      database including known and putative-binding sites. Using a novel algorithm, we
      conducted a large-scale all-pairs similarity search for 1.8 million known and
      potential binding sites in the PDB, and discovered over 14 million similar pairs
      of binding sites. Here, we present the results as a relational database Pocket
      Similarity Search using Multiple-sketches (PoSSuM) including all the discovered
      pairs with annotations of various types. PoSSuM enables rapid exploration of
      similar binding sites among structures with different global folds as well as
      similar ones. Moreover, PoSSuM is useful for predicting the binding ligand for
      unbound structures, which provides important clues for characterizing protein
      structures with unclear functions. The PoSSuM database is freely available at
      http://possum.cbrc.jp/PoSSuM/.

PMID- 22135291
TI  - Rhea--a manually curated resource of biochemical reactions.
AB  - Rhea (http://www.ebi.ac.uk/rhea) is a comprehensive resource of expert-curated
      biochemical reactions. Rhea provides a non-redundant set of chemical
      transformations for use in a broad spectrum of applications, including metabolic
      network reconstruction and pathway inference. Rhea includes enzyme-catalyzed
      reactions (covering the IUBMB Enzyme Nomenclature list), transport reactions and
      spontaneously occurring reactions. Rhea reactions are described using chemical
      species from the Chemical Entities of Biological Interest ontology (ChEBI) and
      are stoichiometrically balanced for mass and charge. They are extensively
      manually curated with links to source literature and other public resources on
      metabolism including enzyme and pathway databases. This cross-referencing
      facilitates the mapping and reconciliation of common reactions and compounds
      between distinct resources, which is a common first step in the reconstruction of
      genome scale metabolic networks and models.

PMID- 22135292
TI  - A comprehensive manually curated protein-protein interaction database for the
      Death Domain superfamily.
AB  - The Death Domain (DD) superfamily, which is one of the largest classes of protein
      interaction modules, plays a pivotal role in apoptosis, inflammation, necrosis
      and immune cell signaling pathways. Because aberrant or inappropriate DD
      superfamily-mediated signaling events are associated with various human diseases,
      such as cancers, neurodegenerative diseases and immunological disorders, the
      studies in these fields are of great biological and clinical importance. To
      facilitate the understanding of the molecular mechanisms by which the DD
      superfamily is associated with biological and disease processes, we have
      developed the DD database (http://www.deathdomain.org), a manually curated
      database that aims to offer comprehensive information on protein-protein
      interactions (PPIs) of the DD superfamily. The DD database was created by
      manually curating 295 peer-reviewed studies that were published in the
      literature; the current version documents 175 PPI pairs among the 99 DD
      superfamily proteins. The DD database provides a detailed summary of the DD
      superfamily proteins and their PPI data. Users can find in-depth information that
      is specified in the literature on relevant analytical methods, experimental
      resources and domain structures. Our database provides a definitive and valuable
      tool that assists researchers in understanding the signaling network that is
      mediated by the DD superfamily.

PMID- 22135293
TI  - The Genomes OnLine Database (GOLD) v.4: status of genomic and metagenomic
      projects and their associated metadata.
AB  - The Genomes OnLine Database (GOLD, http://www.genomesonline.org/) is a
      comprehensive resource for centralized monitoring of genome and metagenome
      projects worldwide. Both complete and ongoing projects, along with their
      associated metadata, can be accessed in GOLD through precomputed tables and a
      search page. As of September 2011, GOLD, now on version 4.0, contains information
      for 11,472 sequencing projects, of which 2907 have been completed and their
      sequence data has been deposited in a public repository. Out of these complete
      projects, 1918 are finished and 989 are permanent drafts. Moreover, GOLD contains
      information for 340 metagenome studies associated with 1927 metagenome samples.
      GOLD continues to expand, moving toward the goal of providing the most
      comprehensive repository of metadata information related to the projects and
      their organisms/environments in accordance with the Minimum Information about any
      (x) Sequence specification and beyond.

PMID- 22135294
TI  - NONCODE v3.0: integrative annotation of long noncoding RNAs.
AB  - Facilitated by the rapid progress of high-throughput sequencing technology, a
      large number of long noncoding RNAs (lncRNAs) have been identified in mammalian
      transcriptomes over the past few years. LncRNAs have been shown to play key roles
      in various biological processes such as imprinting control, circuitry controlling
      pluripotency and differentiation, immune responses and chromosome dynamics.
      Notably, a growing number of lncRNAs have been implicated in disease etiology.
      With the increasing number of published lncRNA studies, the experimental data on
      lncRNAs (e.g. expression profiles, molecular features and biological functions)
      have accumulated rapidly. In order to enable a systematic compilation and
      integration of this information, we have updated the NONCODE database
      (http://www.noncode.org) to version 3.0 to include the first integrated
      collection of expression and functional lncRNA data obtained from re-annotated
      microarray studies in a single database. NONCODE has a user-friendly interface
      with a variety of search or browse options, a local Genome Browser for
      visualization and a BLAST server for sequence-alignment search. In addition,
      NONCODE provides a platform for the ongoing collation of ncRNAs reported in the
      literature. All data in NONCODE are open to users, and can be downloaded through
      the website or obtained through the SOAP API and DAS services.

PMID- 22135295
TI  - Metastases suppressor NME2 associates with telomere ends and telomerase and
      reduces telomerase activity within cells.
AB  - Analysis of chromatin-immunoprecipitation followed by sequencing (ChIP-seq)
      usually disregards sequence reads that do not map within binding positions
      (peaks). Using an unbiased approach, we analysed all reads, both that mapped and
      ones that were not included as part of peaks. ChIP-seq experiments were performed
      in human lung adenocarcinoma and fibrosarcoma cells for the metastasis suppressor
      non-metastatic 2 (NME2). Surprisingly, we identified sequence reads that uniquely
      represented human telomere ends in both cases. In vivo presence of NME2 at
      telomere ends was validated using independent methods and as further evidence we
      found intranuclear association of NME2 and the telomere repeat binding factor 2.
      Most remarkably, results demonstrate that NME2 associates with telomerase and
      reduces telomerase activity in vitro and in vivo, and sustained NME2 expression
      resulted in reduced telomere length in aggressive human cancer cells. Anti
      metastatic function of NME2 has been demonstrated in human cancers, however,
      mechanisms are poorly understood. Together, findings reported here suggest a
      novel role for NME2 as a telomere binding protein that can alter telomerase
      function and telomere length. This presents an opportunity to investigate
      telomere-related interactions in metastasis suppression.

PMID- 22135296
TI  - VectorBase: improvements to a bioinformatics resource for invertebrate vector
      genomics.
AB  - VectorBase (http://www.vectorbase.org) is a NIAID-supported bioinformatics
      resource for invertebrate vectors of human pathogens. It hosts data for nine
      genomes: mosquitoes (three Anopheles gambiae genomes, Aedes aegypti and Culex
      quinquefasciatus), tick (Ixodes scapularis), body louse (Pediculus humanus),
      kissing bug (Rhodnius prolixus) and tsetse fly (Glossina morsitans). Hosted data
      range from genomic features and expression data to population genetics and
      ontologies. We describe improvements and integration of new data that expand our
      taxonomic coverage. Releases are bi-monthly and include the delivery of
      preliminary data for emerging genomes. Frequent updates of the genome browser
      provide VectorBase users with increasing options for visualizing their own high
      throughput data. One major development is a new population biology resource for
      storing genomic variations, insecticide resistance data and their associated
      metadata. It takes advantage of improved ontologies and controlled vocabularies.
      Combined, these new features ensure timely release of multiple types of data in
      the public domain while helping overcome the bottlenecks of bioinformatics and
      annotation by engaging with our user community.

PMID- 22135297
TI  - TarBase 6.0: capturing the exponential growth of miRNA targets with experimental
      support.
AB  - As the relevant literature and the number of experiments increase at a super
      linear rate, databases that curate and collect experimentally verified microRNA
      (miRNA) targets have gradually emerged. These databases attempt to provide
      efficient access to this wealth of experimental data, which is scattered in
      thousands of manuscripts. Aim of TarBase 6.0 (http://www.microrna.gr/tarbase) is
      to face this challenge by providing a significant increase of available miRNA
      targets derived from all contemporary experimental techniques (gene specific and
      high-throughput), while incorporating a powerful set of tools in a user-friendly
      interface. TarBase 6.0 hosts detailed information for each miRNA-gene
      interaction, ranging from miRNA- and gene-related facts to information specific
      to their interaction, the experimental validation methodologies and their
      outcomes. All database entries are enriched with function-related data, as well
      as general information derived from external databases such as UniProt, Ensembl
      and RefSeq. DIANA microT miRNA target prediction scores and the relevant
      prediction details are available for each interaction. TarBase 6.0 hosts the
      largest collection of manually curated experimentally validated miRNA-gene
      interactions (more than 65,000 targets), presenting a 16.5-175-fold increase over
      other available manually curated databases.

PMID- 22135298
TI  - PhosphoSitePlus: a comprehensive resource for investigating the structure and
      function of experimentally determined post-translational modifications in man and
      mouse.
AB  - PhosphoSitePlus (http://www.phosphosite.org) is an open, comprehensive, manually
      curated and interactive resource for studying experimentally observed post
      translational modifications, primarily of human and mouse proteins. It
      encompasses 1,30,000 non-redundant modification sites, primarily phosphorylation,
      ubiquitinylation and acetylation. The interface is designed for clarity and ease
      of navigation. From the home page, users can launch simple or complex searches
      and browse high-throughput data sets by disease, tissue or cell line. Searches
      can be restricted by specific treatments, protein types, domains, cellular
      components, disease, cell types, cell lines, tissue and sequences or motifs. A
      few clicks of the mouse will take users to substrate pages or protein pages with
      sites, sequences, domain diagrams and molecular visualization of side-chains
      known to be modified; to site pages with information about how the modified site
      relates to the functions of specific proteins and cellular processes and to
      curated information pages summarizing the details from one record. PyMOL and
      Chimera scripts that colorize reactive groups on residues that are modified can
      be downloaded. Features designed to facilitate proteomic analyses include
      downloads of modification sites, kinase-substrate data sets, sequence logo
      generators, a Cytoscape plugin and BioPAX download to enable pathway
      visualization of the kinase-substrate interactions in PhosphoSitePlus(r).

PMID- 22135299
TI  - Structural, energetic and dynamic properties of guanine(C8)-thymine(N3) cross
      links in DNA provide insights on susceptibility to nucleotide excision repair.
AB  - The one-electron oxidation of guanine in DNA by carbonate radical anions, a
      decomposition product of peroxynitrosocarbonate which is associated with the
      inflammatory response, can lead to the formation of intrastrand cross-links
      between guanine and thymine bases [Crean et al. (Oxidation of single-stranded
      oligonucleotides by carbonate radical anions: generating intrastrand cross-links
      between guanine and thymine bases separated by cytosines. Nucleic Acids Res.
      2008; 36: 742-755.)]. These involve covalent bonds between the C8 positions of
      guanine (G*) and N3 of thymine (T*) in 5'-d(...G*pT*...) and 5'-d(...G*pCpT*...)
      sequence contexts. We have performed nucleotide excision repair (NER) experiments
      in human HeLa cell extracts which show that the G*CT* intrastrand cross-link is
      excised with approximately four times greater efficiency than the G*T* cross-link
      embedded in 135-mer DNA duplexes. In addition, thermal melting studies reveal
      that both lesions significantly destabilize duplex DNA, and that the
      destabilization induced by the G*CT* cross-link is considerably greater.
      Consistent with this difference in NER, our computations show that both lesions
      dynamically distort and destabilize duplex DNA. They disturb Watson-Crick base
      pairing and base-stacking interactions, and cause untwisting and minor groove
      opening. These structural perturbations are much more pronounced in the G*CT*
      than in the G*T* cross-link. Our combined experimental and computational studies
      provide structural and thermodynamic understanding of the features of the damaged
      duplexes that produce the most robust NER response.

PMID- 22135300
TI  - Structural and functional insights into DNA-end processing by the archaeal HerA
      helicase-NurA nuclease complex.
AB  - Helicase-nuclease systems dedicated to DNA end resection in preparation for
      homologous recombination (HR) are present in all kingdoms of life. In
      thermophilic archaea, the HerA helicase and NurA nuclease cooperate with the
      highly conserved Mre11 and Rad50 proteins during HR-dependent DNA repair. Here we
      show that HerA and NurA must interact in a complex with specific subunit
      stoichiometry to process DNA ends efficiently. We determine crystallographically
      that NurA folds in a toroidal dimer of intertwined RNaseH-like domains. The
      central channel of the NurA dimer is too narrow for double-stranded DNA but
      appears well suited to accommodate one or two strands of an unwound duplex. We
      map a critical interface of the complex to an exposed hydrophobic epitope of NurA
      abutting the active site. Based upon the presented evidence, we propose
      alternative mechanisms of DNA end processing by the HerA-NurA complex.

PMID- 22135301
TI  - BacMap: an up-to-date electronic atlas of annotated bacterial genomes.
AB  - Originally released in 2005, BacMap is an electronic, interactive atlas of fully
      sequenced bacterial genomes. It contains fully labeled, zoomable and searchable
      chromosome maps for essentially all sequenced prokaryotic (archaebacterial and
      eubacterial) species. Each map can be zoomed to the level of individual genes and
      each gene is hyperlinked to a richly annotated gene card. The latest release of
      BacMap (http://bacmap.wishartlab.com/) now contains data for more than 1700
      bacterial species (~10* more than the 2005 release), corresponding to more than
      2800 chromosome and plasmid maps. All bacterial genome maps are now supplemented
      with separate prophage genome maps as well as separate tRNA and rRNA maps. Each
      bacterial chromosome entry in BacMap also contains graphs and tables on a variety
      of gene and protein statistics. Likewise, every bacterial species entry contains
      a bacterial 'biography' card, with taxonomic details, phenotypic details, textual
      descriptions and images (when available). Improved data browsing and searching
      tools have also been added to allow more facile filtering, sorting and display of
      the chromosome maps and their contents.

PMID- 22135302
TI  - DiseaseMeth: a human disease methylation database.
AB  - DNA methylation is an important epigenetic modification for genomic regulation in
      higher organisms that plays a crucial role in the initiation and progression of
      diseases. The integration and mining of DNA methylation data by methylation
      specific PCR and genome-wide profiling technology could greatly assist the
      discovery of novel candidate disease biomarkers. However, this is difficult
      without a comprehensive DNA methylation repository of human diseases. Therefore,
      we have developed DiseaseMeth, a human disease methylation database
      (http://bioinfo.hrbmu.edu.cn/diseasemeth). Its focus is the efficient storage and
      statistical analysis of DNA methylation data sets from various diseases.
      Experimental information from over 14,000 entries and 175 high-throughput data
      sets from a wide number of sources have been collected and incorporated into
      DiseaseMeth. The latest release incorporates the gene-centric methylation data of
      72 human diseases from a variety of technologies and platforms. To facilitate
      data extraction, DiseaseMeth supports multiple search options such as gene ID and
      disease name. DiseaseMeth provides integrated gene methylation data based on
      cross-data set analysis for disease and normal samples. These can be used for in
      depth identification of differentially methylated genes and the investigation of
      gene-disease relationship.

PMID- 22135303
TI  - GADD45alpha inhibition of DNMT1 dependent DNA methylation during homology
      directed DNA repair.
AB  - In this work, we examine regulation of DNA methyltransferase 1 (DNMT1) by the DNA
      damage inducible protein, GADD45alpha. We used a system to induce homologous
      recombination (HR) at a unique double-strand DNA break in a GFP reporter in
      mammalian cells. After HR, the repaired DNA is hypermethylated in recombinant
      clones showing low GFP expression (HR-L expressor class), while in high expressor
      recombinants (HR-H clones) previous methylation patterns are erased. GADD45alpha,
      which is transiently induced by double-strand breaks, binds to chromatin
      undergoing HR repair. Ectopic overexpression of GADD45alpha during repair
      increases the HR-H fraction of cells (hypomethylated repaired DNA), without
      altering the recombination frequency. Conversely, silencing of GADD45alpha
      increases methylation of the recombined segment and amplifies the HR-L expressor
      (hypermethylated) population. GADD45alpha specifically interacts with the
      catalytic site of DNMT1 and inhibits methylation activity in vitro. We propose
      that double-strand DNA damage and the resulting HR process involves precise,
      strand selected DNA methylation by DNMT1 that is regulated by GADD45alpha. Since
      GADD45alpha binds with high avidity to hemimethylated DNA intermediates, it may
      also provide a barrier to spreading of methylation during or after HR repair.

PMID- 22135304
TI  - A novel zinc-finger nuclease platform with a sequence-specific cleavage module.
AB  - Zinc-finger nucleases (ZFNs) typically consist of three to four zinc fingers
      (ZFs) and the non-specific DNA-cleavage domain of the restriction endonuclease
      FokI. In this configuration, the ZFs constitute the binding module and the FokI
      domain the cleavage module. Whereas new binding modules, e.g. TALE sequences,
      have been considered as alternatives to ZFs, no efforts have been undertaken so
      far to replace the catalytic domain of FokI as the cleavage module in ZFNs. Here,
      we have fused a three ZF array to the restriction endonuclease PvuII to generate
      an alternative ZFN. While PvuII adds an extra element of specificity when
      combined with ZFs, ZF-PvuII constructs must be designed such that only PvuII
      sites with adjacent ZF-binding sites are cleaved. To achieve this, we introduced
      amino acid substitutions into PvuII that alter K(m) and k(cat) and increase
      fidelity. The optimized ZF-PvuII fusion constructs cleave DNA at addressed sites
      with a >1000-fold preference over unaddressed PvuII sites in vitro as well as in
      cellula. In contrast to the 'analogous' ZF-FokI nucleases, neither excess of
      enzyme over substrate nor prolonged incubation times induced unaddressed cleavage
      in vitro. These results present the ZF-PvuII platform as a valid alternative to
      conventional ZFNs.

PMID- 22135305
TI  - DOMMINO: a database of macromolecular interactions.
AB  - With the growing number of experimentally resolved structures of macromolecular
      complexes, it becomes clear that the interactions that involve protein structures
      are mediated not only by the protein domains, but also by various non-structured
      regions, such as interdomain linkers, or terminal sequences. Here, we present
      DOMMINO (http://dommino.org), a comprehensive database of macromolecular
      interactions that includes the interactions between protein domains, interdomain
      linkers, N- and C-terminal regions and protein peptides. The database complements
      SCOP domain annotations with domain predictions by SUPERFAMILY and is
      automatically updated every week. The database interface is designed to provide
      the user with a three-stage pipeline to study macromolecular interactions: (i) a
      flexible search that can include a PDB ID, type of interaction, SCOP family of
      interacting proteins, organism name, interaction keyword and a minimal threshold
      on the number of contact pairs; (ii) visualization of subunit interaction
      network, where the user can investigate the types of interactions within a
      macromolecular assembly; and (iii) visualization of an interface structure
      between any pair of the interacting subunits, where the user can highlight
      several different types of residues within the interfaces as well as study the
      structure of the corresponding binary complex of subunits.

PMID- 22135306
TI  - Identification of a core set of signature cell cycle genes whose relative order
      of time to peak expression is conserved across species.
AB  - A cell division cycle is a well-coordinated process in eukaryotes with cell cycle
      genes exhibiting a periodic expression over time. There is considerable interest
      among cell biologists to determine genes that are periodic in multiple organisms
      and whether such genes are also evolutionarily conserved in their relative order
      of time to peak expression. Interestingly, periodicity is not well-conserved
      evolutionarily. A conservative estimate of a number of periodic genes common to
      fission yeast (Schizosaccharomyces pombe) and budding yeast (Saccharomyces
      cerevisiae) ('core set FB') is 35, while those common to fission yeast and humans
      (Homo sapiens) ('core set FH') is 24. Using a novel statistical methodology, we
      discover that the relative order of peak expression is conserved in ~80% of FB
      genes and in ~40% of FH genes. We also discover that the order is evolutionarily
      conserved in six genes which are potentially the core set of signature cell cycle
      genes. These include ace2 (a transcription factor) and polo-kinase plo1, which
      are well-known hubs of early M-phase clusters, cdc18 a key component of pre
      replication complexes, mik1 which is critical for the establishment and
      maintenance of DNA damage check point, and histones hhf1 and hta2.

PMID- 22135307
TI  - Endogenous cannabinoid system regulates intestinal barrier function in vivo
      through cannabinoid type 1 receptor activation.
AB  - The deleterious effects of stress on the gastrointestinal tract seem to be mainly
      mediated by the induction of intestinal barrier dysfunction and subsequent subtle
      mucosal inflammation. Cannabinoid 1 receptor (CB1R) is expressed in the mammalian
      gut under physiological circumstances. The aim of this investigation is to study
      the possible role of CB1R in the maintenance of mucosal homeostasis after stress
      exposure. CB1R knockout mice (CB1R(-/-)) and their wild-type (WT) counterparts
      were exposed to immobilization and acoustic (IA) stress for 2 h per day during 4
      consecutive days. Colonic protein expression of the inducible forms of the nitric
      oxide synthase and cyclooxygenase (NOS2 and COX2), IgA production, permeability
      to (51)Cr-EDTA, and bacterial translocation to mesenteric lymph nodes were
      evaluated. Stress exposure induced greater expression of proinflammatory enzymes
      NOS2 and COX2 in colonic mucosa of CB1R(-/-) mice when compared with WT animals.
      These changes were related with a greater degree of colonic barrier dysfunction
      in CB1R(-/-) animals determined by 1) a significantly lower IgA secretion, 2)
      higher paracellular permeability to (51)Cr-EDTA, and 3) higher bacterial
      translocation, both under basal conditions and after IA stress exposure.
      Pharmacological antagonism with rimonabant reproduced stress-induced increase of
      proinflammatory enzymes in the colon described in CB1R(-/-) mice. In conclusion,
      CB1R exerts a protective role in the colon in vivo through the regulation of
      intestinal secretion of IgA and paracellular permeability. Pharmacological
      modulation of cannabinoid system within the gastrointestinal tract might be
      therapeutically useful in conditions on which intestinal inflammation and barrier
      dysfunction takes place after exposure to stress.

PMID- 22135308
TI  - Expression profiling identifies novel gene targets and functions for Pdx1 in the
      duodenum of mature mice.
AB  - Transcription factor pancreatic and duodenal homeobox 1 (Pdx1) plays an essential
      role in the pancreas to regulate its development and maintain proper islet
      function. However, the functions of Pdx1 in mature small intestine are less
      known. We aimed to investigate the intestinal role of Pdx1 by profiling the
      expression of genes differentially regulated in response to inactivation of Pdx1
      specifically in the intestinal epithelium. Pdx1 was conditionally inactivated in
      the intestinal epithelium of Pdx1(flox/flox);VilCre mice. Total RNA was isolated
      from the first 5 cm of the small intestine from mature Pdx1(flox/flox);VilCre and
      littermate control mice. Microarray analysis identified 86 probe sets
      representing 68 genes significantly upregulated or downregulated 1.5-fold or
      greater in Pdx(flox/flox);VilCre mice maintained under standard conditions.
      Ingenuity Pathway Analysis revealed that functions of the differentially
      expressed genes are significantly associated with metabolism of nutrients
      including lipids and iron. Network analysis examining the interactions among the
      differentially expressed genes further supports the notion that Pdx1 may modulate
      metabolism of lipids and iron from mature intestinal epithelium. Following forced
      oil feeding, Pdx1(flox/flox);VilCre mice showed diminished lipid staining in the
      duodenal epithelium and decreased serum triglyceride levels, indicating reduced
      lipid absorption compared with control duodenal epithelium. Blood samples from
      Pdx1(flox/flox);VilCre mice have significantly lower mean values for mean
      corpuscular volume and mean corpuscular hemoglobin, consistent with iron
      deficiency. The absence of nonheme iron in the villous epithelium and lamina
      propria of Pdx1(flox/flox);VilCre duodenum indicates that the duodenal epithelium
      lacking Pdx1 may have defects in importing iron through enterocytes, resulting in
      iron deficiency in Pdx1(flox/flox);VilCre mice.

PMID- 22135309
TI  - Interleukin-18 facilitates neutrophil transmigration via myosin light chain
      kinase-dependent disruption of occludin, without altering epithelial
      permeability.
AB  - Compromised epithelial barrier function and tight junction alterations are
      hallmarks of a number of gastrointestinal disorders, including inflammatory bowel
      disease (IBD). Increased levels of IL-18 have been observed in mucosal samples
      from Crohn's disease and ulcerative colitis patients. Remarkably, several reports
      have demonstrated that immunological or genetic blockage of IL-18 ameliorates the
      severity of colitis in multiple in vivo models of IBD. Nevertheless, the effects
      of IL-18 on intestinal epithelial barrier function remain unclear. We
      hypothesized that IL-18 could disrupt intestinal epithelial barrier structure and
      function, thus contributing to tissue damage in the context of IBD. The aims of
      the present study were to determine the effects of IL-18 on epithelial barrier
      structure and function and to characterize the mechanisms involved in these
      modulatory properties. Human colonic epithelial Caco-2 monolayers were
      coincubated with IL-18 for 24 h and processed for immunocytochemistry,
      immunoblotting, quantitative PCR, and permeability measurements (transepithelial
      resistance, FITC-dextran fluxes, and bacterial translocation). Our findings
      indicate that IL-18 selectively disrupts tight junctional occludin, without
      affecting the distribution pattern of claudin-4, claudin-5, zonula occludens-1,
      or E-cadherin. This effect coincided with a significant increase in myosin light
      chain kinase (MLCK) protein levels and activity. Pharmacological inhibition of
      MLCK and NF-kappaB prevented IL-18-induced loss of occludin. Although too subtle
      to alter paracellular permeability, these fine changes correlated with an MLCK
      dependent increase in neutrophil transepithelial migration. In conclusion, our
      data suggest that IL-18 may potentiate inflammation in the context of IBD by
      facilitating neutrophil transepithelial migration via MLCK-dependent disruption
      of tight junctional occludin.

PMID- 22135310
TI  - Coexpression of ecto-5'-nucleotidase/CD73 with specific NTPDases differentially
      regulates adenosine formation in the rat liver.
AB  - Ectonucleotidases modulate purinergic signaling by hydrolyzing ATP to adenosine.
      Here we characterized the impact of the cellular distribution of hepatic
      ectonucleotidases, namely nucleoside triphosphate diphosphohydrolase
      (NTPDase)1/CD39, NTPDase2/CD39L1, NTPDase8, and ecto-5'-nucleotidase/CD73, and of
      their specific biochemical properties, on the levels of P1 and P2 receptor
      agonists, with an emphasis on adenosine-producing CD73. Immunostaining and enzyme
      histochemistry showed that the distribution of CD73 (protein and AMPase activity)
      overlaps partially with those of NTPDase1, -2, and -8 (protein levels and ATPase
      and ADPase activities) in normal rat liver. CD73 is expressed in fibroblastic
      cells located underneath vascular endothelial cells and smooth muscle cells,
      which both express NTPDase1, in portal spaces in a distinct fibroblast population
      next to NTPDase2-positive portal fibroblasts, and in bile canaliculi, together
      with NTPDase8. In fibrotic rat livers, CD73 protein expression and activity are
      redistributed but still overlap with the NTPDases mentioned. The ability of the
      observed combinations of ectonucleotidases to generate adenosine over time was
      evaluated by reverse-phase HPLC with the recombinant rat enzymes at high
      "inflammatory" (500 MUM) and low "physiological" (1 MUM) ATP concentrations.
      Overall, ATP was rapidly converted to adenosine by the NTPDase1+CD73 combination,
      but not by the NTPDase2+CD73 combination. In the presence of NTPDase8 and CD73,
      ATP was sequentially dephosphorylated to the CD73 inhibitor ADP, and then to AMP,
      thus resulting in a delayed formation of adenosine. In conclusion, the specific
      cellular cocompartmentalization of CD73 with hepatic NTPDases is not redundant
      and may lead to the differential activation of P1 and P2 receptors, under normal
      and fibrotic conditions.

PMID- 22135311
TI  - Sodium intake, ACE inhibition, and progression to ESRD.
AB  - High sodium intake limits the antihypertensive and antiproteinuric effects of
      angiotensin-converting enzyme (ACE) inhibitors in patients with CKD; however,
      whether dietary sodium also associates with progression to ESRD is unknown. We
      conducted a post hoc analysis of the first and second Ramipril Efficacy in
      Nephropathy trials to evaluate the association of sodium intake with proteinuria
      and progression to ESRD among 500 CKD patients without diabetes who were treated
      with ramipril (5 mg/d) and monitored with serial 24-hour urinary sodium and
      creatinine measurements. Urinary sodium/creatinine excretion defined low (<100
      mEq/g), medium (100 to <200 mEq/g), and high (>=200 mEq/g) sodium intake. During
      a follow-up of >4.25 years, 92 individuals (18.4%) developed ESRD. Among those
      with low, medium, and high sodium intakes, the incidence of ESRD was 6.1 (95%
      confidence interval [95% CI], 3.8-9.7), 7.9 (95% CI, 6.1-10.2), and 18.2 (95% CI,
      11.3-29.3) per 100 patient-years, respectively (P<0.001). Patients with high
      dietary sodium exhibited a blunted antiproteinuric effect of ACE inhibition
      despite similar BP among groups. Each 100-mEq/g increase in urinary
      sodium/creatinine excretion associated with a 1.61-fold (95% CI, 1.15-2.24)
      higher risk for ESRD; adjusting for baseline proteinuria attenuated this
      association to 1.38-fold (95% CI, 0.95-2.00). This association was independent
      from BP but was lost after adjusting for changes in proteinuria. In summary,
      among patients with CKD but without diabetes, high dietary salt (>14 g daily)
      seems to blunt the antiproteinuric effect of ACE inhibitor therapy and increase
      the risk for ESRD, independent of BP control.

PMID- 22135312
TI  - The renal mononuclear phagocytic system.
AB  - The renal mononuclear phagocytic system, conventionally composed of macrophages
      (Mo) and dendritic cells (DCs), plays a central role in health and disease of the
      kidney. Overlapping definitions of renal DCs and Mo, stemming from historically
      separate research tracks and the lack of experimental tools to specifically study
      the roles of these cells in vivo, have generated confusion and controversy,
      however, regarding their immunologic function in the kidney. This brief review
      provides an appraisal of the current state of knowledge of the renal mononuclear
      phagocytic system interpreted from the perspective of immunologic function.
      Physical characteristics, ontogeny, and known functions of the main subsets of
      renal mononuclear phagocytes as they relate to homeostasis, surveillance against
      injury and infection, and immune-mediated inflammatory injury and repair within
      the kidney are described. Gaps and inconsistencies in current knowledge are used
      to create a roadmap of key questions to be answered in future research.

PMID- 22135313
TI  - APOL1 risk variants predict histopathology and progression to ESRD in HIV-related
      kidney disease.
AB  - With earlier institution of antiretroviral therapy, kidney diseases other than
      HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes
      for these diseases are typically worse among those infected with HIV, but the
      reasons for this are not clear. Here, we examined the role of APOL1 risk variants
      in predicting renal histopathology and progression to ESRD in 98 HIV-infected
      African Americans with non-HIVAN kidney disease on biopsy. We used survival
      analysis to determine time to ESRD associated with APOL1 genotype. Among the 29
      patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had
      hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1
      risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had
      FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN
      and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to
      ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly
      three-fold higher risk for ESRD compared with those with one or zero risk alleles
      (P=0.03). In summary, these data demonstrate an association between APOL1
      variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible
      use for APOL1 genotyping to help guide the care of HIV-infected patients.

PMID- 22135314
TI  - GPR48 increases mineralocorticoid receptor gene expression.
AB  - Aldosterone and the mineralocorticoid receptor (MR) are critical to the
      maintenance of electrolyte and BP homeostasis. Mutations in the MR cause
      aldosterone resistance known as pseudohypoaldosteronism type 1 (PHA1); however,
      some cases consistent with PHA1 do not exhibit known gene mutations, suggesting
      the possibility of alternative genetic variants. We observed that G protein
      coupled receptor 48 (Gpr48/Lgr4) hypomorphic mutant (Gpr48(m/m)) mice had
      hyperkalemia and increased water loss and salt excretion despite elevated plasma
      aldosterone levels, suggesting aldosterone resistance. When we challenged the
      mice with a low-sodium diet, these features became more obvious; the mice also
      developed hyponatremia and increased renin expression and activity, resembling a
      mild state of PHA1. There was marked renal downregulation of MR and its
      downstream targets (e.g., the alpha-subunit of the amiloride-sensitive epithelial
      sodium channel), which could provide a mechanism for the aldosterone resistance.
      We identified a noncanonical cAMP-responsive element located in the MR promoter
      and demonstrated that GPR48 upregulates MR expression via the cAMP/protein kinase
      A pathway in vitro. Taken together, our data demonstrate that GPR48 enhances
      aldosterone responsiveness by activating MR expression, suggesting that GPR48
      contributes to homeostasis of electrolytes and BP and may be a candidate gene for
      PHA1.

PMID- 22135315
TI  - Neighborhood location, rurality, geography, and outcomes of peritoneal dialysis
      patients in the United States.
AB  - BACKGROUND: The adjusted 5-year survival for dialysis patients in the United
      States is 33%-35%, and patients treated with peritoneal dialysis (PD) have a high
      risk of transfer to hemodialysis (HD). No data are available on the effect of
      neighborhood characteristics or regional differences on the outcomes of PD
      patients in the United States. METHODS: We analyzed the relationships of selected
      patient demographics, socio-economic characteristics of the dialysis unit's
      neighborhood, "rurality," and geographic location with transfer to HD and with a
      composite outcome of transfer to HD or death, for all PD patients in the United
      States who, between 2004 and 2009, used supplies manufactured by Baxter
      Healthcare (n = 58 700). RESULTS: Over a median follow-up of 18.7 months, 29% of
      patients transferred to HD (median time to HD transfer: 49 months), and 54%
      reached the composite outcome. More than 20% of the events occurred within the
      first 90 days of PD start. The risk for each of the study outcomes was higher for
      patients who had received any previous treatment with HD, for those treated in
      units located in areas with a higher proportion of black residents, and for those
      living in remote rural areas. Furthermore, the risk for reaching either of the
      study outcomes was consistently lower for patients treated in units located in
      California, Alaska, Hawaii, Guam, the Mariana Islands, and American Samoa.
      CONCLUSIONS: We observed significant regional differences in the outcomes of PD
      patients in the United States that have not previously been reported.
      Understanding the differences in clinical practice that underlie these regional
      differences might help to further improve PD outcomes.

PMID- 22135316
TI  - Intermittent peritoneal dialysis: urea kinetic modeling and implications of
      residual kidney function.
AB  - BACKGROUND: Intermittent peritoneal dialysis (IPD) is an old strategy that has
      generally been eclipsed, in the home setting, by daily peritoneal therapies.
      However, for a select group of patients with exhausted vascular access or
      inability to receive PD at home, in-center IPD may remain an option or may serve
      as an incremental strategy before initiation of full-dose PD. We investigated the
      residual kidney clearance requirements necessary to allow thrice-weekly IPD
      regimens to meet current adequacy targets. METHODS: The 3-pore model of
      peritoneal transport was used to examine 2 thrice-weekly IPD dialysis modalities:
      5 - 6 dwells with 10 - 12 L total volume (low-dose IPD), and 50% tidal with 20 -
      24 L total volume (high-dose IPD). We assumed an 8-hour dialysis duration and
      1.5% dextrose solution, with a 2-L fill volume, except in tidal mode. The PD
      Adequest application (version 2.0: Baxter Healthcare Corporation, Deerfield, IL,
      USA) and typical patient kinetic parameters derived from a large dataset [data on
      file from Treatment Adequacy Review for Gaining Enhanced Therapy (Baxter
      Healthcare Corporation)] were used to model urea clearances. The minimum
      glomerular filtration rate (GFR) required to achieve a total weekly urea Kt/V of
      1.7 was calculated. RESULTS: In the absence of any dialysis, the minimum residual
      GFR necessary to achieve a weekly urea Kt/V of 1.7 was 9.7 mL/min/1.73 m(2).
      Depending on membrane transport type, the low-dose IPD modality met urea
      clearance targets for patients with a GFR between 6.0 mL/min/1.73 m(2) and 7.6
      mL/min/1.73 m(2). Similarly, the high-dose IPD modality met the urea clearance
      target for patients with a GFR between 4.7 mL/min/1.73 m(2) and 6.5 mL/min/1.73
      m(2). CONCLUSIONS: In patients with residual GFR of at least 7.6 mL/min/1.73
      m(2), thrice-weekly low-dose IPD (10 L) achieved a Kt/V urea of 1.7 across all
      transport types. Increasing the IPD volume resulted in a decreased residual GFR
      requirement of 4.7 mL/min/1.73 m(2) (24 L, 50% tidal). In patients with residual
      kidney function and dietary compliance, IPD may be a viable strategy in certain
      clinical situations.

PMID- 22135317
TI  - Idiopathic atrial fibrillation revisited in a large longitudinal clinical cohort.
AB  - AIMS: An age of 60 years is often used as cut-off for the diagnosis of idiopathic
      atrial fibrillation (AF). We investigated the importance of age and atrial size
      in patients with idiopathic AF and AF patients with isolated hypertension.
      METHODS AND RESULTS: Out of 3978 AF patients in the Euro Heart Survey on AF with
      known follow-up, 119 (3%) patients had idiopathic AF. We disregarded age and
      atrial size when selecting idiopathic AF patients since the atria may enlarge by
      AF itself. For comparison, we selected 152 patients with isolated hypertension
      from the database. A total of 57 (48%) of the patients were older than 60 years.
      Persistent or permanent AF was more prevalent in the older idiopathic AF patients
      (34% in the age <60 vs. 66% in the age >60 years group, P= 0.002) but mean
      duration of known AF did not differ between these groups [310 days (inter
      quartile range, IQR) 60-1827) vs. 430 days (IQR 88-1669), P= 0.824]. Left atrial
      size did not differ significantly in relation to age (1.50 +/- 0.29 mm/kg/m2 in
      the age <60 vs. 1.56 +/- 0.31 mm/kg/m2 in the age >60 years group, P= 0.742).
      Only two paroxysmal AF patients progressed to permanent AF. No cardiovascular
      events occurred during the 1-year follow-up. In contrast, strokes occurred in
      five patients (6%) with isolated hypertension despite similar clinical profile
      and comparable atrial size as idiopathic AF patients. CONCLUSION: Idiopathic AF
      may present at advanced age and is even then not associated with significant
      atrial enlargement, AF progression, or an adverse short-term prognosis. In
      contrast, elevated blood pressure even when found in the absence of significant
      atrial remodelling, seems of prognostic importance.

PMID- 22135318
TI  - Non-contact mapping system accurately localizes right-sided accessory pathways in
      type B Wolff-Parkinson-White syndrome.
AB  - AIMS: Ablation of right-sided accessory pathways (APs) is sometimes challenging
      because several anatomical features of the tricuspid annulus (TA) and surrounding
      structures differ from those of the mitral annulus. This study investigated the
      electrophysiological characteristics and efficacy of a non-contact mapping (NCM)
      system for catheter ablation of right-sided APs. METHODS AND RESULTS: We examined
      nine APs in six consecutive patients who underwent catheter ablation of right
      sided APs with NCM. In Case 6, we compared NCM with contact activation mapping.
      Three of six patients had two APs, and one of these had previously failed
      ablation. We observed atrial activation during sinus rhythm or atrial pacing
      using a multiple-electrode array (MEA) deployed in the right atrium near the TA.
      Non-contact mapping identified the AP location as a peri-TA breakout point that
      appeared prior to or simultaneously with the delta wave onset in all APs. In Case
      6 we confirmed that the peri-TA breakout identified by NCM corresponded to the
      earliest ventricular activation identified by contact mapping. We successfully
      ablated nine APs by radiofrequency (RF) energy application to the breakout sites,
      while one AP located just above the pole of the MEA required additional
      conventionally guided mapping and ablation. The mean RF duration was 189.8 +/-
      119.0 s. After 33.2 +/- 9.4 months of follow-up, one para-hisian AP and one right
      lateral AP recurred, but these were successfully ablated in a second procedure
      using NCM. CONCLUSION: Non-contact mapping was able to identify the location of
      right-sided APs accurately and quickly.

PMID- 22135320
TI  - Public health and welfare.

PMID- 22135319
TI  - The effect of atrial preference pacing on paroxysmal atrial fibrillation
      incidence in myotonic dystrophy type 1 patients: a prospective, randomized,
      single-bind cross-over study.
AB  - AIMS: Atrial Preference Pacing (APP) is a pacemaker (PM) algorithm that supports
      a continuous atrial stimulation instead of a spontaneous atrial rhythm to prevent
      supraventricular tachyarrhythmias. The role of the APP in the prevention of
      atrial fibrillation (AF) is still controversial. The aim of our study was to
      evaluate the effect of preventive atrial pacing on AF incidence in myotonic
      dystrophy type I patients during a 12-month follow-up period. METHODS AND
      RESULTS: We studied 40 patients with myotonic dystrophy type 1 (MD1) who
      underwent dual-chamber PM implantation for first- and second-degree
      atrioventricular block. After a 1-month stabilization period, they were
      randomized to APP algorithm programmed OFF or ON for 6 months each, using a cross
      over design. The number of AF episodes during active treatment (APP ON phases)
      was lower than those registered during no treatment (APP OFF phases). No
      statistically significant difference was found in AF episodes duration between
      the two phases. During the APP OFF phases and APP ON phases, the atrial pacing
      percentage was 0 and 98%, respectively, while the ventricular pacing percentage
      did not show statistically significant difference (10 vs. 8%, P =0.2). Atrial
      premature beats count was significantly greater during APP OFF phases than during
      APP ON phases. Lead parameters remained stable over time and there were no lead
      related complications. CONCLUSIONS: Based on these 12-month follow-up data, it is
      concluded that APP is an efficacy algorithm for preventing paroxysmal AF in MD1
      patients who underwent dual-chamber PM implantation for atrioventricular
      conduction disorders.

PMID- 22135321
TI  - Examining organizational change in primary care practices: experiences from using
      ethnographic methods.
AB  - BACKGROUND: Qualitative methods are an important part of the primary care
      researcher's toolkit providing a nuanced view of the complexity in primary care
      reform and delivery. Ethnographic research is a comprehensive approach to
      qualitative data collection, including observation, in-depth interviews and
      document analysis. Few studies have been published outlining methodological
      issues related to ethnography in this setting. OBJECTIVE: This paper examines
      some of the challenges of conducting an ethnographic study in primary care
      setting in Canada, where there recently have been major reforms to traditional
      methods of organizing primary care services. METHODS: This paper is based on an
      ethnographic study set in primary care practices in Ontario, Canada, designed to
      investigate changes to organizational and clinical routines in practices
      undergoing transition to new, interdisciplinary Family Health Teams (FHTs). The
      study was set in six new FHTs in Ontario. This paper is a reflexive examination
      of some of the challenges encountered while conducting an ethnographic study in a
      primary care setting. RESULTS: Our experiences in this study highlight some
      potential benefits of and difficulties in conducting an ethnographic study in
      family practice. Our study design gave us an opportunity to highlight the changes
      in routines within an organization in transition. A study with a clinical
      perspective requires training, support, a mixture of backgrounds and perspectives
      and ongoing communication. CONCLUSIONS: Despite some of the difficulties, the
      richness of this method has allowed the exploration of a number of additional
      research questions that emerged during data analysis.

PMID- 22135322
TI  - The five hepatitis viruses.

PMID- 22135324
TI  - The nuclear receptor PPARbeta/delta programs muscle glucose metabolism in
      cooperation with AMPK and MEF2.
AB  - To identify new gene regulatory pathways controlling skeletal muscle energy
      metabolism, comparative studies were conducted on muscle-specific transgenic
      mouse lines expressing the nuclear receptors peroxisome proliferator-activated
      receptor alpha (PPARalpha; muscle creatine kinase [MCK]-PPARalpha) or
      PPARbeta/delta (MCK-PPARbeta/delta). MCK-PPARbeta/delta mice are known to have
      enhanced exercise performance, whereas MCK-PPARalpha mice perform at low levels.
      Transcriptional profiling revealed that the lactate dehydrogenase b (Ldhb)/Ldha
      gene expression ratio is increased in MCK-PPARbeta/delta muscle, an isoenzyme
      shift that diverts pyruvate into the mitochondrion for the final steps of glucose
      oxidation. PPARbeta/delta gain- and loss-of-function studies in skeletal myotubes
      demonstrated that PPARbeta/delta, but not PPARalpha, interacts with the exercise
      inducible kinase AMP-activated protein kinase (AMPK) to synergistically activate
      Ldhb gene transcription by cooperating with myocyte enhancer factor 2A (MEF2A) in
      a PPARbeta/delta ligand-independent manner. MCK-PPARbeta/delta muscle was shown
      to have high glycogen stores, increased levels of GLUT4, and augmented capacity
      for mitochondrial pyruvate oxidation, suggesting a broad reprogramming of glucose
      utilization pathways. Lastly, exercise studies demonstrated that MCK
      PPARbeta/delta mice persistently oxidized glucose compared with nontransgenic
      controls, while exhibiting supranormal performance. These results identify a
      transcriptional regulatory mechanism that increases capacity for muscle glucose
      utilization in a pattern that resembles the effects of exercise training.

PMID- 22135327
TI  - Using simulation to further best practices in nursing leadership.

PMID- 22135323
TI  - A TRPC5-regulated calcium signaling pathway controls dendrite patterning in the
      mammalian brain.
AB  - Transient receptor potential (TRP) channels have been implicated as sensors of
      diverse stimuli in mature neurons. However, developmental roles for TRP channels
      in the establishment of neuronal connectivity remain largely unexplored. Here, we
      identify an essential function for TRPC5, a member of the canonical TRP
      subfamily, in the regulation of dendrite patterning in the mammalian brain.
      Strikingly, TRPC5 knockout mice harbor long, highly branched granule neuron
      dendrites with impaired dendritic claw differentiation in the cerebellar cortex.
      In vivo RNAi analyses suggest that TRPC5 regulates dendrite morphogenesis in the
      cerebellar cortex in a cell-autonomous manner. Correlating with impaired dendrite
      patterning in the cerebellar cortex, behavioral analyses reveal that TRPC5
      knockout mice have deficits in gait and motor coordination. Finally, we uncover
      the molecular basis of TRPC5's function in dendrite patterning. We identify the
      major protein kinase calcium/calmodulin-dependent kinase II beta (CaMKIIbeta) as
      a critical effector of TRPC5 function in neurons. Remarkably, TRPC5 forms a
      complex specifically with CaMKIIbeta, but not the closely related kinase
      CaMKIIalpha, and thereby induces the CaMKIIbeta-dependent phosphorylation of the
      ubiquitin ligase Cdc20-APC at the centrosome. Accordingly, centrosomal CaMKIIbeta
      signaling mediates the ability of TRPC5 to regulate dendrite morphogenesis in
      neurons. Our findings define a novel function for TRPC5 that couples calcium
      signaling to a ubiquitin ligase pathway at the centrosome and thereby
      orchestrates dendrite patterning and connectivity in the brain.

PMID- 22135328
TI  - Low-dose corticosteroids to treat septic shock: a critical literature review.
AB  - Septic shock is the 13th leading cause of death in the United States. The rate of
      severe sepsis nearly doubled and mortality increased more than 60% during the 10
      year period ending in 2003. Systemic inflammatory response syndrome has
      noninfectious and infectious causes. Noninfectious ones include burns, trauma,
      severe pancreatitis, and therapy with monoclonal antibodies or immunomodulatory
      drugs such as interleukin 2. Progression from sepsis syndrome to septic shock is
      caused by a series of immune responses. As an infectious injury progresses, host
      activation of the coagulation, immunological, and stress response systems ensues,
      resulting in tissue hypoperfusion and organ failure. Early studies with small
      numbers of patients suggest that treatment with low-dose corticosteroids has
      marked beneficial effects on shock reversal, the immune system, and the
      hemodynamic profile. Low-dose corticosteroids should only be administered to a
      subset of patients with septic shock who are unresponsive to fluid replacement
      and vasopressor therapy.

PMID- 22135329
TI  - Nurse-led implementation of a safe and effective intravenous insulin protocol in
      a medical intensive care unit.
AB  - BACKGROUND: Recent evidence has linked tight glucose control to worsened clinical
      outcomes among adults in intensive care units. OBJECTIVE: To evaluate the
      effectiveness and safety of a nurse-led intravenous insulin protocol designed to
      achieve conservative blood glucose control in patients in a medical intensive
      care unit. METHODS: A nurse-led intravenous insulin protocol was developed,
      targeting blood glucose levels at 110 to 149 mg/dL. Hypoglycemia was defined as a
      blood glucose level less than 70 mg/dL. Patients admitted to the medical
      intensive care unit who required an insulin infusion were enrolled in the study.
      Blood glucose levels in those patients were compared with levels in 153
      historical control patients admitted to the unit in the 12 months before the
      protocol was implemented who required an insulin infusion. RESULTS: Ninety-six
      patients were enrolled and treated with the protocol. The protocol and control
      groups had similar characteristics at baseline. More measurements in the protocol
      group than in the control group (46.3% vs 36.1%, P<.001) were within the target
      glucose range (110-149 mg/dL). Hyperglycemia (blood glucose >=200 mg/dL) occurred
      less often in the protocol group than in the control group (14.8% vs 20.1%,
      P=.003). Hypoglycemic events (blood glucose <70 mg/dL) also occurred less often
      in the protocol group (0.07% vs 0.83%, P<.001). CONCLUSIONS: Implementation of a
      nurse-led, conservative intravenous insulin protocol in the medical intensive
      care unit is effective and safe and markedly reduces the rate of hypoglycemia.

PMID- 22135330
TI  - Postoperative nausea and vomiting in adults: implications for critical care.
AB  - Postoperative nausea and vomiting is a dreaded, uncomfortable, and unpleasant
      patient experience that is also a factor contributing to adverse outcomes in
      postoperative recovery. The key to management of this concern is to identify high
      risk patients and to develop a systematic method of assessment, intervention, and
      evaluation within the perianesthesia care continuum. This discussion outlines the
      wide range of pharmacological and alternative therapies that are available in
      clinical practice with a case study to illustrate incorporation of these
      interventions in critically ill patients.

PMID- 22135331
TI  - Achieving quality patient-ventilator management: advancing evidence-based nursing
      care.
AB  - This article presents suggestions for nurses to gain skill, competence, and
      comfort in caring for critically ill patients receiving mechanical ventilatory
      support, with a specific focus on education strategies and building communication
      skills with these challenging nonverbal patients. Engaging in evidence-based
      practice projects at the unit level and participating in or leading research
      studies are key ways nurses can contribute to improving outcomes for patients
      receiving mechanical ventilation. Suggestions are offered for evidence-based
      practice projects and possible research studies to improve outcomes and advance
      the science in an effort to achieve quality patient-ventilator management in
      intensive care units.

PMID- 22135332
TI  - A nurse's experience being intubated and receiving mechanical ventilation.
AB  - A nurse with a history of childhood asthma describes her experiences with
      intubation and mechanical ventilation. It is important for nurses to recognize
      that mechanical ventilation is very stressful for patients and for the patients'
      families. It is essential for nurses to keep the patient as the focus of their
      care. A key part of that focus is to reorient patients who are receiving
      mechanical ventilation frequently.

PMID- 22135333
TI  - Using a nursing productivity committee to achieve cost savings and improve
      staffing levels and staff satisfaction.
AB  - Challenged by rising costs, higher registered nurse vacancy rates and declining
      staff morale, a Nursing Productivity Committee was formed to analyze productive
      and nonproductive hours and seek improvements in our staffing models and
      scheduling processes. The changes implemented led to lower nurse to patient
      ratios, better control of labor costs, elimination of agency staff, greater staff
      satisfaction, and introduction of new technologies. Nurse managers, nursing
      supervisors, and frontline staff are now more knowledgeable and empowered to use
      creative solutions to manage their budgets and schedules in these times of
      fluctuating census and varying vacancy rates.

PMID- 22135334
TI  - Setting goals for pain management when using a behavioral scale: example with the
      critical-care pain observation tool.

PMID- 22135335
TI  - Focusing on mind, body, and spirit while caring for patients and their families.

PMID- 22135337
TI  - I am a critical care nurse.

PMID- 22135338
TI  - Inhaled treprostinil for the treatment of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension is a progressive disease characterized by
      vascular proliferation and vasoconstriction of the small pulmonary arteries that
      eventually leads to right-sided heart failure and death. Patients often initially
      have symptoms such as shortness of breath, fatigue, and edema; later in the
      disease, presyncope and syncope are common. Patients with progressive pulmonary
      arterial hypertension despite oral therapy and/or with severe disease typically
      require treatment with a prostanoid. Inhaled treprostinil (Tyvaso) is a
      prostacyclin analog indicated for the treatment of pulmonary arterial
      hypertension to increase walk distance in patients with symptoms classified as
      New York Heart Association functional class III. Inhaled treprostinil was
      approved by the Food and Drug Administration in July 2009. This article provides
      a brief overview of the pathophysiology of pulmonary arterial hypertension and
      reviews the mechanism of action, key clinical data, and the practical management
      of inhaled treprostinil in patients with pulmonary arterial hypertension.

PMID- 22135339
TI  - Critical care staff nurses: empowerment, certification, and intent to leave.
AB  - BACKGROUND: Certification is a voluntary process that is used to recognize
      specialized knowledge and skills. Little research has been focused on staff
      nurses with specialty certification. OBJECTIVE: To determine if perceptions of
      empowerment and intent to leave the position and the profession differed among
      staff nurses who were certified by the American Association of Critical-Care
      Nurses, nurses certified by other certifying organizations, and nurses who were
      not certified. METHODS: A comparative descriptive study was used to analyze the
      results of a 2007 to 2008 Web-based survey of members of the association. Data
      were available on 4268 staff nurses. RESULTS: Total empowerment scores and intent
      to leave either the position or the profession did not differ between nurses who
      were certified and those who were not. However, perceptions of informal power,
      opportunity, and support did differ between the 2 groups. CONCLUSIONS: The
      differences between nurses who were certified and those who were not may be
      related to variables other than certification. Further research and theoretical
      model testing is needed to determine the value of certification.

PMID- 22135340
TI  - Optimal management of shivering during therapeutic hypothermia after cardiac
      arrest.
AB  - Both pharmacological and nonpharmacological methods are used to control shivering
      in therapeutic hypothermia. An evidence-based protocol based on the most current
      research has been developed for the management of shivering during therapeutic
      hypothermia. Meperidine is the drug of choice and provides the greatest reduction
      in the shivering threshold. Other effective pharmacological agents recommended
      for reducing the threshold include dexmedetomidine, midazolam, fentanyl, and
      magnesium sulfate. In addition, skin counterwarming techniques, such as use of an
      air-circulating blanket, are effective nonpharmacological methods for reducing
      shivering when used in conjunction with medication. As a last resort,
      neuromuscular blocking agents are considered appropriate therapy for management
      of refractory shivering.

PMID- 22135341
TI  - A mechanistic role for type III IFN-lambda1 in asthma exacerbations mediated by
      human rhinoviruses.
AB  - RATIONALE: Human rhinoviruses (HRV) are the leading cause of upper respiratory
      infections and have been postulated to trigger asthma exacerbations. However,
      whether HRV are detected during crises because upper respiratory infections often
      accompany asthma attacks, or because they specifically elicit exacerbations, is
      unclear. Moreover, although several hypotheses have been advanced to explain
      virus-induced exacerbations, their mechanism remains unclear. OBJECTIVES: To
      determine the role of HRV in pediatric asthma exacerbations and the mechanisms
      mediating wheezing. METHODS: We prospectively studied 409 children with asthma
      presenting with upper respiratory infection in the presence or absence of
      wheezing. Candidate viral and immune mediators of illness were compared among
      children with asthma with different degrees of severity of acute asthma.
      MEASUREMENTS AND MAIN RESULTS: HRV infections specifically associated with asthma
      exacerbations, even after adjusting for relevant demographic and clinical
      variables defined a priori (odds ratio, 1.90; 95% confidence interval, 1.21-2.99;
      P = 0.005). No difference in virus titers, HRV species, and inflammatory or
      allergic molecules was observed between wheezing and nonwheezing children
      infected with HRV. Type III IFN-lambda(1) levels were higher in wheezing children
      infected with HRV compared with nonwheezing (P < 0.001) and increased with
      worsening symptoms (P < 0.001). Moreover, after adjusting for IFN-lambda(1),
      children with asthma infected with HRV were no longer more likely to wheeze than
      those who were HRV-negative (odds ratio, 1.18; 95% confidence interval, 0.57
      2.46; P = 0.66). CONCLUSIONS: Our findings suggest that HRV infections in
      children with asthma are specifically associated with acute wheezing, and that
      type III IFN-lambda(1) responses mediate exacerbations caused by HRV. Modulation
      of IFN- lambda(1) should be studied as a therapeutic target for exacerbations
      caused by HRV.

PMID- 22135342
TI  - Regulation of lymphocyte trafficking by CXC chemokine receptor 3 during septic
      shock.
AB  - RATIONALE: Lymphocytes have been shown to facilitate systemic inflammation and
      physiologic dysfunction in experimental models of severe sepsis. Our previous
      studies show that natural killer (NK) cells migrate into the peritoneal cavity
      during intraabdominal sepsis, but the trafficking of NKT and T lymphocytes has
      not been determined. The factors that regulate lymphocyte trafficking during
      sepsis are currently unknown. OBJECTIVES: To ascertain the importance of CXC
      chemokine receptor 3 (CXCR3) as a regulator of lymphocyte trafficking during
      sepsis and determine the contribution of CXCR3-mediated lymphocyte trafficking to
      the pathogenesis of septic shock. METHODS: Lymphocyte trafficking was evaluated
      in control and CXCR3-deficient mice using flow cytometry during sepsis caused by
      cecal ligation and puncture (CLP). Survival, core temperature, cytokine
      production, and bacterial clearance were measured as pathobiological endpoints.
      MEASUREMENTS AND MAIN RESULTS: This study shows that concentrations of the CXCR3
      ligands CXCL9 (monokine induced by interferon gamma, MIG) and CXCL10 (interferon
      gamma-induced protein 10, IP-10) increase in plasma and the peritoneal cavity
      after CLP, peak at 8 hours after infection, and are higher in the peritoneal
      cavity than in plasma. The numbers of CXCR3(+) NK cells progressively decreased
      in spleen after CLP with a concomitant increase within the peritoneal cavity, a
      pattern that was ablated in CXCR3-deficient mice. CXCR3-dependent recruitment of
      T cells was also evident at 16 hours after CLP. Treatment of mice with anti-CXCR3
      significantly attenuated CLP-induced hypothermia, decreased systemic cytokine
      production, and improved survival. CONCLUSIONS: CXCR3 regulates NK- and T-cell
      trafficking during sepsis and blockade of CXCR3 attenuates the pathogenesis of
      septic shock.

PMID- 22135343
TI  - Acute upper airway responses to hypoglossal nerve stimulation during sleep in
      obstructive sleep apnea.
AB  - RATIONALE: Hypoglossal nerve stimulation (HGNS) recruits lingual muscles, reduces
      pharyngeal collapsibility, and treats sleep apnea. OBJECTIVES: We hypothesized
      that graded increases in HGNS relieve pharyngeal obstruction progressively during
      sleep. METHODS: Responses were examined in 30 patients with sleep apnea who were
      implanted with an HGNS system. Current (milliampere) was increased stepwise
      during non-REM sleep. Frequency and pulse width were fixed. At each current
      level, stimulation was applied on alternating breaths, and responses in maximal
      inspiratory airflow (V(I)max) and inspiratory airflow limitation (IFL) were
      assessed. Pharyngeal responses to HGNS were characterized by the current levels
      at which V(I)max first increased and peaked (flow capture and peak flow
      thresholds), and by the V(I)max increase from flow capture to peak
      (DeltaV(I)max). MEASUREMENTS AND MAIN RESULTS: HGNS produced linear increases in
      V(I)max from unstimulated levels at flow capture to peak flow thresholds (215 +/-
      21 to 509 +/- 37 ml/s; mean +/- SE; P < 0.001) with increasing current from 1.05
      +/- 0.09 to 1.46 +/- 0.11 mA. V(I)max increased in all patients and IFL was
      abolished in 57% of patients (non-IFL subgroup). In the non-IFL compared with IFL
      subgroup, the flow response slope was greater (1241 +/- 199 vs. 674 +/- 166
      ml/s/mA; P < 0.05) and the stimulation amplitude at peak flow was lower (1.23 +/-
      0.10 vs. 1.80 +/- 0.20 mA; P < 0.05) without differences in peak flow.
      CONCLUSIONS: HGNS produced marked dose-related increases in airflow without
      arousing patients from sleep. Increases in airflow were of sufficient magnitude
      to eliminate IFL in most patients and IFL and non-IFL subgroups achieved normal
      or near-normal levels of flow, suggesting potential HGNS efficacy across a broad
      range of sleep apnea severity.

PMID- 22135345
TI  - The use of nonphysician providers in adult intensive care units.
AB  - In the United States there are not currently enough critical care-trained
      practitioners to provide care to all critically ill patients. With calls for
      "high-intensity" staffing and 24-hour coverage of our intensive care units, the
      board-certified intensivists we do have are being stretched ever more thin.
      Nonphysician providers (physician assistants and nurse practitioners) are being
      used with increasing frequency in critical care settings to provide care to
      critically ill patients. In this review, we explore the impact of introducing
      nonphysician providers into the adult intensive care unit.

PMID- 22135344
TI  - Cystic fibrosis transmembrane conductance regulator regulates epithelial cell
      response to Aspergillus and resultant pulmonary inflammation.
AB  - RATIONALE: Mutations in the cystic fibrosis transmembrane conductance regulator
      (CFTR) alter epithelial cell (EC) interactions with multiple microbes, such that
      dysregulated inflammation and injury occur with airway colonization in people
      with cystic fibrosis (CF). Aspergillus fumigatus frequently colonizes CF airways,
      but it has been assumed to be an innocent saprophyte; its potential role as a
      cause of lung disease is controversial. OBJECTIVES: To study the interactions
      between Aspergillus and EC, and the role of the fungus in evoking inflammatory
      responses. METHODS: A. fumigatus expressing green fluorescent protein was
      developed for in vitro and in vivo models, which used cell lines and mouse
      tracheal EC. MEASUREMENTS AND MAIN RESULTS: Fungal spores (conidia) are rapidly
      ingested by ECs derived from bronchial cell lines and murine tracheas, supporting
      a role for EC in early airway clearance. Bronchial ECs harboring CFTR mutations
      (DeltaF508) or deletion demonstrate impaired uptake and killing of conidia, and
      ECs with CFTR mutation undergo more conidial-induced apoptosis. Germinated
      (hyphal) forms of the fungus evoke secretion of inflammatory mediators, with CFTR
      mutation resulting in increased airway levels of macrophage inflammatory protein
      2 and KC, and higher lung monocyte chemotactic protein-1. After A. fumigatus
      inhalation, CFTR(-/-) mice develop exaggerated lymphocytic inflammation, mucin
      accumulation, and lung injury. CONCLUSIONS: Data demonstrate a critical role for
      CFTR in mediating EC responses to A. fumigatus. Results suggest that the fungus
      elicits aberrant pulmonary inflammation in the setting of CFTR mutation,
      supporting the potential role of antifungals to halt progressive CF lung disease.

PMID- 22135347
TI  - Transcriptional regulatory circuitries in the human pathogen Candida albicans
      involving sense--antisense interactions.
AB  - Candida albicans, a major human fungal pathogen, usually contains a diploid
      genome, but controls adaptation to a toxic alternative carbon source L-sorbose,
      by the reversible loss of one chromosome 5 (Ch5). We have previously identified
      multiple unique regions on Ch5 that repress the growth on sorbose. In one of the
      regions, the CSU51 gene determining the repressive property of the region was
      identified. We report here the identification of the CSU53 gene from a different
      region on Ch5. Most importantly, we find that CSU51 and CSU53 are associated with
      novel regulatory elements, ASUs, which are embedded within CSUs in an antisense
      configuration. ASUs act opposite to CSUs by enhancing the growth on sorbose. In
      respect to the CSU transcripts, the ASU long antisense transcripts are in lesser
      amounts, are completely overlapped, and are inversely related. ASUs interact with
      CSUs in natural CSU/ASU cis configurations, as well as when extra copies of ASUs
      are placed in trans to the CSU/ASU configurations. We suggest that ASU long
      embedded antisense transcripts modulate CSU sense transcripts.

PMID- 22135348
TI  - Low-pass genome-wide sequencing and variant inference using identity-by-descent
      in an isolated human population.
AB  - Whole-genome sequencing in an isolated population with few founders directly
      ascertains variants from the population bottleneck that may be rare elsewhere. In
      such populations, shared haplotypes allow imputation of variants in unsequenced
      samples without resorting to complex statistical methods as in studies of outbred
      cohorts. We focus on an isolated population cohort from the Pacific Island of
      Kosrae, Micronesia, where we previously collected SNP array and rich phenotype
      data for the majority of the population. We report identification of long regions
      with haplotypes co-inherited between pairs of individuals and methodology to
      leverage such shared genetic content for imputation. Our estimates show that
      sequencing as few as 40 personal genomes allows for inference in up to 60% of the
      3000-person cohort at the average locus. We ascertained a pilot data set of whole
      genome sequences from seven Kosraean individuals, with average 5* coverage. This
      assay identified 5,735,306 unique sites of which 1,212,831 were previously
      unknown. Additionally, these variants are unusually enriched for alleles that are
      rare in other populations when compared to geographic neighbors (published Korean
      genome SJK). We used the presence of shared haplotypes between the seven Kosraen
      individuals to estimate expected imputation accuracy of known and novel
      homozygous variants at 99.6% and 97.3%, respectively. This study presents whole
      genome analysis of a homogenous isolate population with emphasis on optimal rare
      variant inference.

PMID- 22135349
TI  - The structure of genealogies in the presence of purifying selection: a fitness
      class coalescent.
AB  - Compared to a neutral model, purifying selection distorts the structure of
      genealogies and hence alters the patterns of sampled genetic variation. Although
      these distortions may be common in nature, our understanding of how we expect
      purifying selection to affect patterns of molecular variation remains incomplete.
      Genealogical approaches such as coalescent theory have proven difficult to
      generalize to situations involving selection at many linked sites, unless
      selection pressures are extremely strong. Here, we introduce an effective
      coalescent theory (a "fitness-class coalescent") to describe the structure of
      genealogies in the presence of purifying selection at many linked sites. We use
      this effective theory to calculate several simple statistics describing the
      expected patterns of variation in sequence data, both at the sites under
      selection and at linked neutral sites. Our analysis combines a description of the
      allele frequency spectrum in the presence of purifying selection with the
      structured coalescent approach of Kaplan et al. (1988), to trace the ancestry of
      individuals through the distribution of fitnesses within the population. We also
      derive our results using a more direct extension of the structured coalescent
      approach of Hudson and Kaplan (1994). We find that purifying selection leads to
      patterns of genetic variation that are related but not identical to a neutrally
      evolving population in which population size has varied in a specific way in the
      past.

PMID- 22135346
TI  - Obstructive sleep apnea in infants.
AB  - Obstructive sleep apnea in infants has a distinctive pathophysiology, natural
      history, and treatment compared with that of older children and adults. Infants
      have both anatomical and physiological predispositions toward airway obstruction
      and gas exchange abnormalities; including a superiorly placed larynx, increased
      chest wall compliance, ventilation-perfusion mismatching, and ventilatory control
      instability. Congenital abnormalities of the airway, such as laryngomalacia,
      hemangiomas, pyriform aperture stenosis, choanal atresia, and laryngeal webs, may
      also have adverse effects on airway patency. Additional exacerbating factors
      predisposing infants toward airway collapse include neck flexion, airway
      secretions, gastroesophageal reflux, and sleep deprivation. Obstructive sleep
      apnea in infants has been associated with failure to thrive, behavioral deficits,
      and sudden infant death. The proper interpretation of infant polysomnography
      requires an understanding of normative data related to gestation and
      postconceptual age for apnea, arousal, and oxygenation. Direct visualization of
      the upper airway is an important diagnostic modality in infants with obstructive
      apnea. Treatment options for infant obstructive sleep apnea are predicated on the
      underlying etiology, including supraglottoplasty for severe laryngomalacia,
      mandibular distraction for micrognathia, tonsillectomy and/or adenoidectomy,
      choanal atresia repair, and/or treatment of gastroesophageal reflux.

PMID- 22135350
TI  - Patterning of the adult mandibulate mouthparts in the red flour beetle, Tribolium
      castaneum.
AB  - Specialized insect mouthparts, such as those of Drosophila, are derived from an
      ancestral mandibulate state, but little is known about the developmental genetics
      of mandibulate mouthparts. Here, we study the metamorphic patterning of
      mandibulate mouthparts of the beetle Tribolium castaneum, using RNA interference
      to deplete the expression of 13 genes involved in mouthpart patterning. These
      data were used to test three hypotheses related to mouthpart development and
      evolution. First, we tested the prediction that maxillary and labial palps are
      patterned using conserved components of the leg-patterning network. This
      hypothesis was strongly supported: depletion of Distal-less and dachshund led to
      distal and intermediate deletions of these structures while depletion of
      homothorax led to homeotic transformation of the proximal maxilla and labium,
      joint formation required the action of Notch signaling components and odd-skipped
      paralogs, and distal growth and patterning required epidermal growth factor (EGF)
      signaling. Additionally, depletion of abrupt or pdm/nubbin caused fusions of palp
      segments. Second, we tested hypotheses for how adult endites, the inner branches
      of the maxillary and labial appendages, are formed at metamorphosis. Our data
      reveal that Distal-less, Notch signaling components, and odd-skipped paralogs,
      but not dachshund, are required for metamorphosis of the maxillary endites.
      Endite development thus requires components of the limb proximal-distal axis
      patterning and joint segmentation networks. Finally, adult mandible development
      is considered in light of the gnathobasic hypothesis. Interestingly, while EGF
      activity is required for distal, but not proximal, patterning of other
      appendages, it is required for normal metamorphic growth of the mandibles.

PMID- 22135351
TI  - Gene duplication of endothelin 3 is closely correlated with the hyperpigmentation
      of the internal organs (Fibromelanosis) in silky chickens.
AB  - During early development in vertebrates, pluripotent cells are generated from the
      neural crest and migrate according to their presumptive fate. In birds and
      mammals, one of the progeny cells, melanoblasts, generally migrate through a
      dorsolateral route of the trunk region and differentiate to melanocytes. However,
      Silky is an exceptional chicken in which numerous melanoblasts travel via a
      ventral pathway and disperse into internal organs. Finally, these ectopic
      melanocytes induce heavy dermal and visceral melanization known as Fibromelanosis
      (Fm). To identify the genetic basis of this phenotype, we confirmed the mode of
      inheritance of Fm as autosomal dominant and then performed linkage analysis with
      microsatellite markers and sequence-tagged site markers. Using 85 backcross
      progeny from crossing Black Minorca chickens (BM-C) with F(1) individuals between
      White Silky (WS) and BM-C Fm was located on 10.2-11.7 Mb of chicken chromosome
      20. In addition, we noticed a DNA marker that all Silky chickens and the F(1)
      individuals showed heterozygous genotyping patterns, suggesting gene duplication
      in the Fm region. By quantitative real-time PCR assay, Silky line-specific gene
      duplication was detected as an ~130-kb interval. It contained five genes
      including endothelin 3 (EDN3), which encoded a potent mitogen for
      melanoblasts/melanocytes. EDN3 with another three of these duplicated genes in
      Silky chickens expressed almost twofold of those in BM-C. Present results
      strongly suggest that the increase of the expression levels resulting from the
      gene duplication in the Fm region is the trigger of hypermelanization in internal
      organs of Silky chickens.

PMID- 22135352
TI  - A Bayesian antedependence model for whole genome prediction.
AB  - Hierarchical mixed effects models have been demonstrated to be powerful for
      predicting genomic merit of livestock and plants, on the basis of high-density
      single-nucleotide polymorphism (SNP) marker panels, and their use is being
      increasingly advocated for genomic predictions in human health. Two particularly
      popular approaches, labeled BayesA and BayesB, are based on specifying all SNP
      associated effects to be independent of each other. BayesB extends BayesA by
      allowing a large proportion of SNP markers to be associated with null effects. We
      further extend these two models to specify SNP effects as being spatially
      correlated due to the chromosomally proximal effects of causal variants. These
      two models, that we respectively dub as ante-BayesA and ante-BayesB, are based on
      a first-order nonstationary antedependence specification between SNP effects. In
      a simulation study involving 20 replicate data sets, each analyzed at six
      different SNP marker densities with average LD levels ranging from r(2) = 0.15 to
      0.31, the antedependence methods had significantly (P < 0.01) higher accuracies
      than their corresponding classical counterparts at higher LD levels (r(2) > 0.
      24) with differences exceeding 3%. A cross-validation study was also conducted on
      the heterogeneous stock mice data resource (http://mus.well.ox.ac.uk/mouse/HS/)
      using 6-week body weights as the phenotype. The antedependence methods increased
      cross-validation prediction accuracies by up to 3.6% compared to their classical
      counterparts (P < 0.001). Finally, we applied our method to other benchmark data
      sets and demonstrated that the antedependence methods were more accurate than
      their classical counterparts for genomic predictions, even for individuals
      several generations beyond the training data.

PMID- 22135353
TI  - Novel transcript truncating function of Rap1p revealed by synthetic codon
      optimized Ty1 retrotransposon.
AB  - Extensive mutagenesis via massive recoding of retrotransposon Ty1 produced a
      synthetic codon-optimized retrotransposon (CO-Ty1). CO-Ty1 is defective for
      retrotransposition, suggesting a sequence capable of down-regulating
      retrotransposition. We mapped this sequence to a critical ~20-bp region within CO
      Ty1 reverse transcriptase (RT) and confirmed that it reduced Ty1 transposition,
      protein, and RNA levels. Repression was not Ty1 specific; when introduced
      immediately downstream of the green fluorescent protein (GFP) stop codon, GFP
      expression was similarly reduced. Rap1p mediated this down-regulation, as shown
      by mutagenesis and chromatin immunoprecipitation. A regular threefold drop is
      observed in different contexts, suggesting utility for synthetic circuits. A
      large reduction of RNAP II occupancy on the CO-Ty1 construct was observed 3' to
      the identified Rap1p site and a novel 3' truncated RNA species was observed. We
      propose a novel mechanism of transcriptional regulation by Rap1p whereby it
      serves as a transcriptional roadblock when bound to transcription unit sequences.

PMID- 22135354
TI  - An integrated biochemistry and genetics outreach program designed for elementary
      school students.
AB  - Exposure to genetic and biochemical experiments typically occurs late in one's
      academic career. By the time students have the opportunity to select specialized
      courses in these areas, many have already developed negative attitudes toward the
      sciences. Given little or no direct experience with the fields of genetics and
      biochemistry, it is likely that many young people rule these out as potential
      areas of study or career path. To address this problem, we developed a 7-week (~1
      hr/week) hands-on course to introduce fifth grade students to basic concepts in
      genetics and biochemistry. These young students performed a series of
      investigations (ranging from examining phenotypic variation, in vitro enzymatic
      assays, and yeast genetic experiments) to explore scientific reasoning through
      direct experimentation. Despite the challenging material, the vast majority of
      students successfully completed each experiment, and most students reported that
      the experience increased their interest in science. Additionally, the experiments
      within the 7-week program are easily performed by instructors with basic skills
      in biological sciences. As such, this program can be implemented by others
      motivated to achieve a broader impact by increasing the accessibility of their
      university and communicating to a young audience a positive impression of the
      sciences and the potential for science as a career.

PMID- 22135355
TI  - The genetic consequences of spatially varying selection in the panmictic American
      eel (Anguilla rostrata).
AB  - Our understanding of the genetic basis of local adaptation has recently benefited
      from the increased power to identify functional variants associated with
      environmental variables at the genome scale. However, it often remains
      challenging to determine whether locally adaptive alleles are actively maintained
      at intermediate frequencies by spatially varying selection. Here, we evaluate the
      extent to which this particular type of balancing selection explains the
      retention of adaptive genetic variation in the extreme situation of perfect
      panmixia, using the American eel (Anguilla rostrata) as a model. We first
      conducted a genome scan between two samples from opposite ends of a latitudinal
      environmental gradient using 454 sequencing of individually tagged cDNA
      libraries. Candidate SNPs were then genotyped in 992 individuals from 16 sampling
      sites at different life stages of the same cohort (including larvae from the
      Sargasso Sea, glass eels, and 1-year-old individuals) as well as in glass eels of
      the following cohort. Evidence for spatially varying selection was found at 13
      loci showing correlations between allele frequencies and environmental variables
      across the entire species range. Simulations under a multiple-niche Levene's
      model using estimated relative fitness values among genotypes rarely predicted a
      stable polymorphic equilibrium at these loci. Our results suggest that some
      genetic-by-environment interactions detected in our study arise during the
      progress toward fixation of a globally advantageous allele with spatially
      variable effects on fitness.

PMID- 22135356
TI  - The genetic basis of heterosis: multiparental quantitative trait loci mapping
      reveals contrasted levels of apparent overdominance among traits of agronomical
      interest in maize (Zea mays L.).
AB  - Understanding the genetic bases underlying heterosis is a major issue in maize
      (Zea mays L.). We extended the North Carolina design III (NCIII) by using three
      populations of recombinant inbred lines derived from three parental lines
      belonging to different heterotic pools, crossed with each parental line to obtain
      nine families of hybrids. A total of 1253 hybrids were evaluated for grain
      moisture, silking date, plant height, and grain yield. Quantitative trait loci
      (QTL) mapping was carried out on the six families obtained from crosses to
      parental lines following the "classical" NCIII method and with a multiparental
      connected model on the global design, adding the three families obtained from
      crosses to the nonparental line. Results of the QTL detection highlighted that
      most of the QTL detected for grain yield displayed apparent overdominance effects
      and limited differences between heterozygous genotypes, whereas for grain
      moisture predominance of additive effects was observed. For plant height and
      silking date results were intermediate. Except for grain yield, most of the QTL
      identified showed significant additive-by-additive epistatic interactions. High
      correlation observed between heterosis and the heterozygosity of hybrids at
      markers confirms the complex genetic basis and the role of dominance in
      heterosis. An important proportion of QTL detected were located close to the
      centromeres. We hypothesized that the lower recombination in these regions favors
      the detection of (i) linked QTL in repulsion phase, leading to apparent
      overdominance for heterotic traits and (ii) linked QTL in coupling phase,
      reinforcing apparent additive effects of linked QTL for the other traits.

PMID- 22135357
TI  - New insights into the genetics of in vivo induction of maternal haploids, the
      backbone of doubled haploid technology in maize.
AB  - Haploids and doubled haploid (DH) inbred lines have become an invaluable tool for
      maize genetic research and hybrid breeding, but the genetic basis of in vivo
      induction of maternal haploids is still unknown. This is the first study
      reporting comparative quantitative trait locus (QTL) analyses of this trait in
      maize. We determined haploid induction rates (HIR) in testcrosses of a total of
      1061 progenies of four segregating populations involving two temperate haploid
      inducers, UH400 (HIR = 8%) and CAUHOI (HIR = 2%), one temperate and two tropical
      inbreds with HIR = 0%, and up to three generations per population. Mean HIR of
      the populations ranged from 0.6 to 5.2% and strongly deviated from the midparent
      values. One QTL (qhir1) explaining up to p = 66% of the genetic variance was
      detected in bin 1.04 in the three populations involving a noninducer parent and
      the HIR-enhancing allele was contributed by UH400. Segregation ratios of loci in
      bin 1.04 were highly distorted against the UH400 allele in these three
      populations, suggesting that transmission failure of the inducer gamete and
      haploid induction ability are related phenomena. In the CAUHOI * UH400
      population, seven QTL were identified on five chromosomes, with qhir8 on
      chromosome 9 having p > 20% in three generations of this cross. The large-effect
      QTL qhir1 and qhir8 will likely become fixed quickly during inducer development
      due to strong selection pressure applied for high HIR. Hence, marker-based
      pyramiding of small-effect and/or modifier QTL influencing qhir1 and qhir8 may
      help to further increase HIR in maize. We propose a conceptual genetic framework
      for inheritance of haploid induction ability, which is also applicable to other
      dichotomous traits requiring progeny testing, and discuss the implications of our
      results for haploid inducer development.

PMID- 22135358
TI  - Conflicting physiological and genomic cardiopulmonary effects of recruitment
      maneuvers in murine acute lung injury.
AB  - Low tidal volume ventilation, although promoting atelectasis, is a protective
      strategy against ventilator-induced lung injury. Deep inflation (DI) recruitment
      maneuvers restore lung volumes, but potentially compromise lung parenchymal and
      vascular function via repetitive overdistention. Our objective was to examine
      cardiopulmonary physiological and transcriptional consequences of recruitment
      maneuvers. C57/BL6 mice challenged with either PBS or LPS via aspiration were
      placed on mechanical ventilation (5 h) using low tidal volume inflation (TI; 8
      MUl/g) alone or in combination with intermittent DIs (0.75 ml twice/min). Lung
      mechanics during TI ventilation significantly deteriorated, as assessed by forced
      oscillation technique and pressure-volume curves. DI mitigated the TI-induced
      alterations in lung mechanics, but induced a significant rise in right ventricle
      systolic pressures and pulmonary vascular resistances, especially in LPS
      challenged animals. In addition, DI exacerbated the LPS-induced genome-wide lung
      inflammatory transcriptome, with prominent dysregulation of a gene cluster
      involving vascular processes, as well as increases in cytokine concentrations in
      bronchoalveolar lavage fluid and plasma. Gene ontology analyses of right
      ventricular tissue expression profiles also identified inflammatory signatures,
      as well as apoptosis and membrane organization ontologies, as potential elements
      in the response to acute pressure overload. Our results, although confirming the
      improvement in lung mechanics offered by DI, highlight a detrimental impact in
      sustaining inflammatory response and exacerbating lung vascular dysfunction,
      events contributing to increases in right ventricle afterload. These novel
      insights should be integrated into the clinical assessment of the risk/benefit of
      recruitment maneuver strategies.

PMID- 22135359
TI  - Meta-analysis for linear and nonlinear dose-response relations: examples, an
      evaluation of approximations, and software.
AB  - Two methods for point and interval estimation of relative risk for log-linear
      exposure-response relations in meta-analyses of published ordinal categorical
      exposure-response data have been proposed. The authors compared the results of a
      meta-analysis of published data using each of the 2 methods with the results that
      would be obtained if the primary data were available and investigated the
      circumstances under which the approximations required for valid use of each meta
      analytic method break down. They then extended the methods to handle nonlinear
      exposure-response relations. In the present article, methods are illustrated
      using studies of the relation between alcohol consumption and colorectal and lung
      cancer risks from the ongoing Pooling Project of Prospective Studies of Diet and
      Cancer. In these examples, the differences between the results of a meta-analysis
      of summarized published data and the pooled analysis of the individual original
      data were small. However, incorrectly assuming no correlation between relative
      risk estimates for exposure categories from the same study gave biased confidence
      intervals for the trend and biased P values for the tests for nonlinearity and
      between-study heterogeneity when there was strong confounding by other model
      covariates. The authors illustrate the use of 2 publicly available user-friendly
      programs (Stata and SAS) to implement meta-analysis for dose-response data.

PMID- 22135360
TI  - Intercellular protein movement in syncytial Drosophila follicle cells.
AB  - Ring canals connecting Drosophila germline, follicle and imaginal disc cells
      provide direct contact of cytoplasm between cells. To date, little is known about
      the formation, structure, or function of the somatic ring canals present in
      follicle and imaginal disc cells. Here, we show by confocal and electron
      microscopy that Pavarotti kinesin-like protein and Visgun are stable components
      of somatic ring canals. Using live-cell confocal microscopy, we show that somatic
      ring canals form from the stabilization of mitotic cleavage furrows. In contrast
      to germline cells, syncytial follicle cells do not divide synchronously, are not
      maximally branched and their ring canals do not increase in size during egg
      chamber development. We show for the first time that somatic ring canals permit
      exchange of cytoplasmic proteins between follicle cells. These results provide
      insight into the composition and function of ring canals in somatic cells,
      implying a broader functional significance for syncytial organization of cells
      outside the germline.

PMID- 22135361
TI  - Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX
      1.
AB  - Lectin-like oxidized LDL receptor-1 (LOX-1) is a surface scavenger receptor for
      oxidized low-density lipoprotein (oxLDL). Several transcription factors have been
      reported to regulate LOX-1 expression. MicroRNAs are small noncoding RNAs that
      control gene expression, but there have been no reports of LOX-1 expression being
      regulated by microRNAs. Because the microRNA let-7g has been predicted to bind to
      LOX-1 mRNA, we investigated whether let-7g can regulate LOX-1 expression. Our
      experiments first demonstrated that oxLDL can reduce let-7g expression. We later
      confirmed that there is a let-7g binding site on the 3'-untranslated region of
      LOX-1 mRNA. We showed that intracellular Ca(2+)-activated protein kinase C is
      involved in the oxLDL-LOX-1-let-7g pathway. Bioinformatics predicted that the let
      7g promoter has a binding site for the transcriptional repressor OCT-1. We used a
      promoter assay and chromatin immunoprecipitation to confirm this binding.
      Consequently, knockdown of OCT-1 was found to increase let-7g expression.
      Transfection of let-7g inhibited oxLDL-induced LOX-1 and OCT-1 expression, cell
      proliferation and migration. Mice fed with a high-fat diet showed a decrease in
      let-7g and an increase in LOX-1 and OCT-1. A study on humans showed the serum
      levels of let-7g are lower in subjects with hypercholesterolemia compared with
      normal controls. Our findings identify a negative feedback regulation between let
      7g and LOX-1, and indicate that let-7g could be a target to treat cardiovascular
      disease.

PMID- 22135363
TI  - Dynamic association-dissociation and harboring of endogenous mRNAs in stress
      granules.
AB  - In response to environmental stress, cytoplasmic mRNAs aggregate to form stress
      granules (SGs). SGs have mainly been studied indirectly using protein markers,
      but the real-time behavior of endogenous mRNAs in SGs remains uncertain. Here, we
      visualized endogenous cytoplasmic poly(A)(+) mRNAs in living mammalian cells
      using a linear antisense 2'-O-methyl RNA probe. In arsenite-stressed cells,
      endogenous mRNAs aggregated in granules that colocalized with SGs marked by TIA-1
      GFP. Moreover, analysis of mRNA dynamics using fluorescence recovery after
      photobleaching showed that approximately one-third of the endogenous mRNAs in SGs
      was immobile, another one-third was diffusive, and the remaining one-third was in
      equilibrium between binding to and dissociating from SGs, with a time constant of
      approximately 300 seconds. These dynamic characteristics of mRNAs were
      independent of the duration of stress and microtubule integrity. Similar
      characteristics were also observed from fos mRNA labeled with an antisense 2'-O
      methyl RNA probe. Our results revealed the behavior of endogenous mRNAs, and
      indicated that SGs act as dynamic harbors of untranslated poly(A)(+) mRNAs.

PMID- 22135364
TI  - Reconsidering "what works".

PMID- 22135362
TI  - Rescue of Aspergillus nidulans severely debilitating null mutations in ESCRT-0,
      I, II and III genes by inactivation of a salt-tolerance pathway allows
      examination of ESCRT gene roles in pH signalling.
AB  - The Aspergillus pal pathway hijacks ESCRT proteins into ambient pH signalling
      complexes. We show that components of ESCRT-0, ESCRT-I, ESCRT-II and ESCRT-III
      are nearly essential for growth, precluding assessment of null mutants for pH
      signalling or trafficking. This severely debilitating effect is rescued by loss
      of-function mutations in two cation tolerance genes, one of which, sltA, encodes
      a transcription factor whose inactivation promotes hypervacuolation. Exploiting a
      conditional expression sltA allele, we demonstrate that deletion of vps27 (ESCRT
      0), vps23 (ESCRT-I), vps36 (ESCRT-II), or vps20 or vps32 (both ESCRT-III) leads
      to numerous small vacuoles, a phenotype also suppressed by SltA downregulation.
      This situation contrasts with normal vacuoles and vacuole-associated class E
      compartments seen in Saccharomyces cerevisiae ESCRT null mutants. Exploiting the
      suppressor phenotype of sltA(-) mutations, we establish that Vps23, Vps36, Vps20
      and Vps32 are essential for pH signalling. Phosphatidylinositol 3-phosphate
      recognising protein Vps27 (ESCRT-0) is not, consistent with normal pH signalling
      in rabB null mutants unable to recruit Vps34 kinase to early endosomes. In
      contrast to the lack of pH signalling in the absence of Vps20 or Vps32,
      detectable signalling occurs in the absence of ESCRT-III subunit Vps24. Our data
      support a model in which certain ESCRT proteins are recruited to the plasma
      membrane to mediate pH signalling.

PMID- 22135365
TI  - Recent research in science teaching and learning.

PMID- 22135368
TI  - GCAT-SEEKquence: genome consortium for active teaching of undergraduates through
      increased faculty access to next-generation sequencing data.
AB  - To transform undergraduate biology education, faculty need to provide
      opportunities for students to engage in the process of science. The rise of
      research approaches using next-generation (NextGen) sequencing has been
      impressive, but incorporation of such approaches into the undergraduate
      curriculum remains a major challenge. In this paper, we report proceedings of a
      National Science Foundation-funded workshop held July 11-14, 2011, at Juniata
      College. The purpose of the workshop was to develop a regional research
      coordination network for undergraduate biology education (RCN/UBE). The network
      is collaborating with a genome-sequencing core facility located at Pennsylvania
      State University (University Park) to enable undergraduate students and faculty
      at small colleges to access state-of-the-art sequencing technology. We aim to
      create a database of references, protocols, and raw data related to NextGen
      sequencing, and to find innovative ways to reduce costs related to sequencing and
      bioinformatics analysis. It was agreed that our regional network for NextGen
      sequencing could operate more effectively if it were partnered with the Genome
      Consortium for Active Teaching (GCAT) as a new arm of that consortium, entitled
      GCAT-SEEK(quence). This step would also permit the approach to be replicated
      elsewhere.

PMID- 22135369
TI  - Assessment of learning gains associated with independent exam analysis in
      introductory biology.
AB  - This study evaluates the impact of an independent postmidterm question analysis
      exercise on the ability of students to answer subsequent exam questions on the
      same topics. It was conducted in three sections (~400 students/section) of
      introductory biology. Graded midterms were returned electronically, and each
      student was assigned a subset of questions answered incorrectly by more than 40%
      of the class to analyze as homework. The majority of questions were at Bloom's
      application/analysis level; this exercise therefore emphasized learning at these
      higher levels of cognition. Students in each section answered final exam
      questions matched by topic to all homework questions, providing a within-class
      control group for each question. The percentage of students who correctly
      answered the matched final exam question was significantly higher (p < 0.05) in
      the Topic Analysis versus Control Analysis group for seven of 19 questions. We
      identified two factors that influenced activity effectiveness: 1) similarity in
      topic emphasis of the midterm-final exam question pair and 2) quality of the
      completed analysis homework. Our data suggest that this easy-to-implement
      exercise will be useful in large-enrollment classes to help students develop self
      regulated learning skills. Additional strategies to help introductory students
      gain a broader understanding of topic areas are discussed.

PMID- 22135370
TI  - Integrating theory and practice to increase scientific workforce diversity: a
      framework for career development in graduate research training.
AB  - Few, if any, educational interventions intended to increase underrepresented
      minority (URM) graduate students in biological and behavioral sciences are
      informed by theory and research on career persistence. Training and Education to
      Advance Minority Scholars in Science (TEAM-Science) is a program funded by the
      National Institute of General Medical Sciences at the University of Wisconsin
      Madison with the twin goals of increasing the number of URM students entering and
      completing a PhD in BBS and increasing the number of these students who pursue
      academic careers. A framework for career development in graduate research
      training is proposed using social cognitive career theory. Based on this
      framework, TEAM-Science has five core components: 1) mentor training for the
      research advisor, 2) eight consensus-derived fundamental competencies required
      for a successful academic career, 3) career coaching by a senior faculty member,
      4) an individualized career development plan that aligns students' activities
      with the eight fundamental competencies, and 5) a strengths, weaknesses,
      opportunities, and threats personal career analysis. This paper describes the
      theoretical framework used to guide development of these components, the research
      and evaluation plan, and early experience implementing the program. We discuss
      the potential of this framework to increase desired career outcomes for URM
      graduate trainees in mentored research programs and, thereby, strengthen the
      effectiveness of such interventions on participants' career behaviors.

PMID- 22135371
TI  - The C.R.E.A.T.E. approach to primary literature shifts undergraduates' self
      assessed ability to read and analyze journal articles, attitudes about science,
      and epistemological beliefs.
AB  - The C.R.E.A.T.E. (Consider, Read, Elucidate hypotheses, Analyze and interpret
      data, Think of the next Experiment) method uses intensive analysis of primary
      literature in the undergraduate classroom to demystify and humanize science. We
      have reported previously that the method improves students' critical thinking and
      content integration abilities, while at the same time enhancing their self
      reported understanding of "who does science, and why." We report here the results
      of an assessment that addressed C.R.E.A.T.E. students' attitudes about the nature
      of science, beliefs about learning, and confidence in their ability to read,
      analyze, and explain research articles. Using a Likert-style survey administered
      pre- and postcourse, we found significant changes in students' confidence in
      their ability to read and analyze primary literature, self-assessed understanding
      of the nature of science, and epistemological beliefs (e.g., their sense of
      whether knowledge is certain and scientific talent innate). Thus, within a single
      semester, the inexpensive C.R.E.A.T.E. method can shift not just students'
      analytical abilities and understanding of scientists as people, but can also
      positively affect students' confidence with analysis of primary literature, their
      insight into the processes of science, and their beliefs about learning.

PMID- 22135372
TI  - Applying computerized-scoring models of written biological explanations across
      courses and colleges: prospects and limitations.
AB  - Our study explored the prospects and limitations of using machine-learning
      software to score introductory biology students' written explanations of
      evolutionary change. We investigated three research questions: 1) Do scoring
      models built using student responses at one university function effectively at
      another university? 2) How many human-scored student responses are needed to
      build scoring models suitable for cross-institutional application? 3) What
      factors limit computer-scoring efficacy, and how can these factors be mitigated?
      To answer these questions, two biology experts scored a corpus of 2556 short
      answer explanations (from biology majors and nonmajors) at two universities for
      the presence or absence of five key concepts of evolution. Human- and computer
      generated scores were compared using kappa agreement statistics. We found that
      machine-learning software was capable in most cases of accurately evaluating the
      degree of scientific sophistication in undergraduate majors' and nonmajors'
      written explanations of evolutionary change. In cases in which the software did
      not perform at the benchmark of "near-perfect" agreement (kappa > 0.80), we
      located the causes of poor performance and identified a series of strategies for
      their mitigation. Machine-learning software holds promise as an assessment tool
      for use in undergraduate biology education, but like most assessment tools, it is
      also characterized by limitations.

PMID- 22135373
TI  - Active learning not associated with student learning in a random sample of
      college biology courses.
AB  - Previous research has suggested that adding active learning to traditional
      college science lectures substantially improves student learning. However, this
      research predominantly studied courses taught by science education researchers,
      who are likely to have exceptional teaching expertise. The present study
      investigated introductory biology courses randomly selected from a list of
      prominent colleges and universities to include instructors representing a broader
      population. We examined the relationship between active learning and student
      learning in the subject area of natural selection. We found no association
      between student learning gains and the use of active-learning instruction.
      Although active learning has the potential to substantially improve student
      learning, this research suggests that active learning, as used by typical college
      biology instructors, is not associated with greater learning gains. We contend
      that most instructors lack the rich and nuanced understanding of teaching and
      learning that science education researchers have developed. Therefore, active
      learning as designed and implemented by typical college biology instructors may
      superficially resemble active learning used by education researchers, but lacks
      the constructivist elements necessary for improving learning.

PMID- 22135374
TI  - Using clickers to facilitate development of problem-solving skills.
AB  - Classroom response systems, or clickers, have become pedagogical staples of the
      undergraduate science curriculum at many universities. In this study, the
      effectiveness of clickers in promoting problem-solving skills in a genetics class
      was investigated. Students were presented with problems requiring application of
      concepts covered in lecture and were polled for the correct answer. A histogram
      of class responses was displayed, and students were encouraged to discuss the
      problem, which enabled them to better understand the correct answer. Students
      were then presented with a similar problem and were again polled. My results
      indicate that those students who were initially unable to solve the problem were
      then able to figure out how to solve similar types of problems through a
      combination of trial and error and class discussion. This was reflected in
      student performance on exams, where there was a statistically significant
      positive correlation between grades and the percentage of clicker questions
      answered. Interestingly, there was no clear correlation between exam grades and
      the percentage of clicker questions answered correctly. These results suggest
      that students who attempt to solve problems in class are better equipped to solve
      problems on exams.

PMID- 22135375
TI  - Osmosis and diffusion conceptual assessment.
AB  - Biology student mastery regarding the mechanisms of diffusion and osmosis is
      difficult to achieve. To monitor comprehension of these processes among students
      at a large public university, we developed and validated an 18-item Osmosis and
      Diffusion Conceptual Assessment (ODCA). This assessment includes two-tiered
      items, some adopted or modified from the previously published Diffusion and
      Osmosis Diagnostic Test (DODT) and some newly developed items. The ODCA, a
      validated instrument containing fewer items than the DODT and emphasizing
      different content areas within the realm of osmosis and diffusion, better aligns
      with our curriculum. Creation of the ODCA involved removal of six DODT item
      pairs, modification of another six DODT item pairs, and development of three new
      item pairs addressing basic osmosis and diffusion concepts. Responses to ODCA
      items testing the same concepts as the DODT were remarkably similar to responses
      to the DODT collected from students 15 yr earlier, suggesting that student
      mastery regarding the mechanisms of diffusion and osmosis remains elusive.

PMID- 22135376
TI  - Adding an extra dimension to what students see through the light microscope: a
      lab exercise demonstrating critical analysis for microscopy students.
AB  - This article describes an undergraduate lab exercise that demonstrates the
      importance of students thinking critically about what they see through a
      microscope. The students are given growth data from tip-growing organisms that
      suggest the cells grow in a pulsatile manner. The students then critique this
      data in several exercises that incorporate aspects of a problem-based learning
      approach, envisaging growth not just in two dimensions, but in three dimensions.
      For some cells, what appears to be pulsatile growth could also be explained by
      growth at a constant rate up and down in the z-axis. Depending on the diffraction
      pattern generated by the tip of the cell, this movement in the z-axis could go
      undetected. This raises the possibility that pulsatile growth seen in some
      species may be an artifact generated by the limitations of the light microscope.
      Students were subsequently asked to rate their awareness of the need to think
      critically about what they see through a microscope, using a scale of 1 (unaware)
      to 5 (very much aware). Prior to doing the lab exercise, the mean rating was 2.7;
      this increased to 4.4 after the lab. The students also indicated a likelihood of
      being more critical in their thinking in other aspects of their biology
      curriculum.

PMID- 22135377
TI  - The maintenance and disambiguation of object representations depend upon feature
      contrast within and between objects.
AB  - The brain processes many aspects of the visual world separately and in parallel,
      yet we perceive a unified world populated by objects. In order to create such a
      "bound" percept, the visual system must construct object-centered representations
      out of separate features and then maintain the representations across changes in
      space and time. Here, we examine the role of features themselves in maintaining
      and disambiguating the representations of the objects to which they belong. In
      three experiments, we measure how the perceived motion of two objects traversing
      ambiguous trajectories is affected by the contrast between the features and
      surrounding fields, by the contrast between features, and by changes to
      orientation of texture within objects. We report that the maintenance and
      disambiguation of object representations depend on the contrast of the features
      relative to their surrounds and on the extent of feature differences between the
      two objects. These feature dependencies indicate that object representation
      relies on relative response to many stimulus dimensions.

PMID- 22135378
TI  - Precision of working memory for visual motion sequences and transparent motion
      surfaces.
AB  - Recent studies investigating working memory for location, color, and orientation
      support a dynamic resource model. We examined whether this might also apply to
      motion, using random dot kinematograms (RDKs) presented sequentially or
      simultaneously. Mean precision for motion direction declined as sequence length
      increased, with precision being lower for earlier RDKs. Two alternative models of
      working memory were compared specifically to distinguish between the
      contributions of different sources of error that corrupt memory (W. Zhang & S. J.
      Luck, 2008 vs. P. M. Bays, R. F. G. Catalao, & M. Husain, 2009). The latter
      provided a significantly better fit for the data, revealing that decrease in
      memory precision for earlier items is explained by an increase in interference
      from other items in a sequence rather than random guessing or a temporal decay of
      information. Misbinding feature attributes is an important source of error in
      working memory. Precision of memory for motion direction decreased when two RDKs
      were presented simultaneously as transparent surfaces, compared to sequential
      RDKs. However, precision was enhanced when one motion surface was prioritized,
      demonstrating that selective attention can improve recall precision. These
      results are consistent with a resource model that can be used as a general
      conceptual framework for understanding working memory across a range of visual
      features.

PMID- 22135379
TI  - Bile acids in sputum and increased airway inflammation in patients with cystic
      fibrosis.
AB  - BACKGROUND: Up to 80% of patients with cystic fibrosis (CF) may have increased
      gastroesophageal reflux and aspiration of duodenogastric contents into the lungs.
      We aimed to assess aspiration in patients with CF by measuring duodenogastric
      components in induced sputum and to investigate whether the presence of bile
      acids (BAs) in sputum was correlated with disease severity and markers of
      inflammation. METHODS: In 41 patients with CF, 15 healthy volunteers, 29 patients
      with asthma, and 28 patients with chronic cough, sputum was obtained after
      inhalation of hypertonic saline. Sputum supernatant was tested for BA and
      neutrophil elastase. Spirometry and BMI were assessed on the day of sputum
      collection. RESULTS: Two of 15 healthy patients (13%), eight of 29 patients (28%)
      with asthma, four of 28 patients (14%) with chronic cough, and 23 of 41 patients
      (56%) with CF had BA in sputum. BA concentrations were similar in patients who
      are positive for BA with genotype F508del homozygote, F508del heterozygote, and
      other CF mutations and were not related with BMI and age. Patients with CF with
      BA in sputum had a higher concentration of neutrophil elastase compared with
      patients without BA in sputum (31.25 [20.33-54.78] MUg/mL vs 14.45 [7.11-27.88]
      MUg/mL, P < .05). There was a significant correlation between BA concentrations
      and dynamic lung volumes (FEV(1) % predicted [r = -0.53, P < .01], FVC% [r = 
      0.59, P < .01]) as well as with number of days of antibiotic IV treatment (r =
      0.58, P < .01). CONCLUSIONS: BAs are present in the sputum of more than one-half
      of patients with CF, suggesting aspiration of duodenogastric contents. Aspiration
      of BA was associated with increased airway inflammation. In patients with BA
      aspiration, the levels of BA were clearly associated with the degree of lung
      function impairment as well as the need for IV antibiotic treatment.

PMID- 22135380
TI  - Limited short-term steroid responsiveness is associated with thickening of
      bronchial basement membrane in severe asthma.
AB  - BACKGROUND: The clinical manifestations of bronchial remodeling in asthma and the
      potential impact of this process on lung function remain unclear. We aimed to
      determine whether the presence of pathologic features of airway remodeling in
      patients with asthma was associated with steroid responsiveness in the short
      term. METHODS: Sixty-three consecutive patients with severe asthma with chronic
      airflow impairment (post-bronchodilator FEV(1) < 80% predicted values) were
      recruited, clinically characterized, and had an initial bronchoscopy where
      endobronchial biopsy and BAL were performed. BAL cellular content was reported
      and reticular basement membrane (RBM) thickness was measured by validated
      repeated measures. Patients were then treated with 1 mg/kg/d of methyl
      prednisone, directly administered IV, for 10 days. A threshold of 15% FEV(1)
      improvement was used to discriminate responsive (group 1) and refractory patients
      (group 2). RESULTS: Thirty-eight patients had a steroid responsiveness > 15%
      (group 1) and a thinner RBM at the biopsy level (5.78 +/- 2.0 MUm vs 7.60 +/- 2.2
      MUm; P = .001) compared with nonsteroid responsive group 2 patients as defined.
      The best predictors for being unresponsive were no long-term treatment with oral
      steroids and increased RBM thickness. The associated receiver operating
      characteristic curve indicated that RBM thickness could predict steroid
      responsiveness below 15% with an area under the curve of 0.747 (P = .0002) at a
      threshold of 7 MUm. CONCLUSIONS: Features of airway remodeling are associated
      with limited short-term steroid responsiveness in severe asthma.

PMID- 22135381
TI  - Direct comparison of three natriuretic peptides for prediction of short- and long
      term mortality in patients with community-acquired pneumonia.
AB  - BACKGROUND: Early and accurate risk stratification for patients with community
      acquired pneumonia (CAP) is an unmet clinical need. METHODS: We enrolled 341
      unselected patients presenting to the ED with CAP in whom blinded measurements of
      N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-atrial
      natriuretic peptide (MR-proANP), and B-type natriuretic peptide (BNP) were
      performed. The potential of these natriuretic peptides to predict short- (30-day)
      and long-term mortality was compared with the pneumonia severity index (PSI) and
      CURB-65 (confusion, urea plasma level, respiratory rate, BP, age over 65 years).
      The median follow-up was 942 days. RESULTS: NT-proBNP, MR-proANP, and BNP levels
      at presentation were higher in short-term (median 4,882 pg/mL vs 1,133 pg/mL; 426
      pmol/L vs 178 pmol/L; 436 pg/mL vs 155 pg/mL, all P < .001) and long-term
      nonsurvivors (3,515 pg/mL vs 548 pg/mL; 283 pmol/L vs 136 pmol/L; 318 pg/mL vs
      103 pg/mL, all P < .001) as compared with survivors. Receiver operating
      characteristics analysis to quantify the prognostic accuracy showed comparable
      areas under the curve for the three natriuretic peptides to PSI for short-term
      (PSI 0.76, 95% CI, 0.71-0.81; NT-proBNP 0.73, 95% CI, 0.67-0.77; MR-proANP 0.72,
      95% CI, 0.67-0.77; BNP 0.68, 95% CI, 0.63-0.73) and long-term (PSI 0.72, 95% CI,
      0.66-0.77; NT-proBNP 0.75, 95% CI, 0.70-0.80; MR-proANP 0.73, 95% CI, 0.67-0.77,
      BNP 0.70, 95% CI, 0.65-0.75) mortality. In multivariable Cox-regression analysis,
      NT-proBNP remained an independent mortality predictor (hazard ratio 1.004, 95%
      CI, 1.00-1.01, P = .02 for short-term; hazard ratio 1.004, 95% CI, 1.00-1.01, P =
      .001 for long-term, increase of 300 pg/mL). A categorical approach combining PSI
      point values and NT-pro-BNP levels adequately identified patients at low, medium,
      and high short- and long-term mortality risk. CONCLUSIONS: Natriuretic peptides
      are simple and powerful predictors of short- and long-term mortality for patients
      with CAP. Their prognostic accuracy is comparable to PSI.

PMID- 22135382
TI  - Epigenetic augmentation of the macrophage inflammatory protein 2/C-X-C chemokine
      receptor type 2 axis through histone H3 acetylation in injured peripheral nerves
      elicits neuropathic pain.
AB  - Although there is growing evidence showing that the involvement of chemokines in
      the pathogenesis of neuropathic pain is associated with neuroinflammation, the
      details are unclear. We investigated the C-X-C chemokine ligand type 2
      [macrophage inflammatory protein 2 (MIP-2)]/C-X-C chemokine receptor type 2
      (CXCR2) axis and epigenetic regulation of these molecules in neuropathic pain
      after peripheral nerve injury. Expression of MIP-2 and CXCR2 were up-regulated
      and localized on accumulated neutrophils and macrophages in the injured sciatic
      nerve (SCN) after partial sciatic nerve ligation (PSL). Perineural injection of
      MIP-2-neutralizing antibody (anti-MIP-2) or the CXCR2 antagonist N-(2
      bromophenyl)-N'-(2-hydroxy-4-nitrophenyl)urea (SB225002) prevented PSL-induced
      tactile allodynia and thermal hyperalgesia. Perineural injection of recombinant
      MIP-2 elicited neuropathic pain-like behaviors. Anti-MIP-2 suppressed neutrophil
      accumulation in the SCN after PSL. Neutrophil depletion by intraperitoneal
      injection of Ly6G antibody attenuated PSL-induced neuropathic pain. Both anti-MIP
      2 and SB225002 suppressed up-regulation of inflammatory cytokines and chemokines
      in the injured SCN. In addition, acetylation of histone H3 [lysine (Lys9)
      acetylated histone H3 (AcK9-H3)] on the promoter region of MIP-2 and CXCR2 was
      increased in the injured SCN after PSL. Expression of AcK9-H3 was observed in the
      nuclei of neutrophils and macrophages surrounding the epineurium. Administration
      of the histone acetyltransferase inhibitor anacardic acid suppressed the up
      regulation of MIP-2 and CXCR2 in the SCN after PSL and resulted in the prevention
      of PSL-induced neuropathic pain. Taken together, these results show that
      augmentation of the MIP-2/CXCR2 axis by hyperacetylation of histone H3 on the
      promoter region of MIP-2 and CXCR2 located in the injured peripheral nerve
      elicits chronic neuroinflammation through neutrophil accumulation, leading to
      neuropathic pain.

PMID- 22135383
TI  - Roles of the M1 muscarinic acetylcholine receptor subtype in the regulation of
      basal ganglia function and implications for the treatment of Parkinson's disease.
AB  - Antagonists of the muscarinic acetylcholine receptors (mAChRs) were among the
      first treatments for Parkinson's disease. However, the clinical utility of mAChR
      antagonists is limited by adverse effects associated with the blockade of
      multiple mAChR subtypes. Understanding the roles of specific mAChR subtypes in
      regulating basal ganglia and motor function could lead to the development of
      novel agents that have antiparkinsonian activity with fewer adverse effects.
      Using the novel, highly selective M1 antagonist N-[3-oxo-3-[4-(4-pyridinyl)-1
      piperazinyl]propyl]-2,1,3-benzothiadiazole-4-sulfonamide (VU0255035) and the M1
      positive allosteric modulator benzylquinolone carboxylic acid, we investigated
      the roles of M1 receptors in cholinergic excitation and regulation of synaptic
      transmission in striatal medium spiny neurons (MSNs) and neurons in the
      subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr).
      Electrophysiological studies demonstrate that M1 activation has excitatory
      effects on MSNs but plays little or no role in mAChR-mediated increases in firing
      frequency or the regulation of synaptic transmission in STN and SNr neurons. On
      the basis of this profile, M1-selective antagonists may have weak
      antiparkinsonian activity but would not have the full efficacy observed in
      nonselective mAChR antagonists. Consistent with this, the M1-selective antagonist
      VU0255035 partially reversed reserpine-induced akinesia and decreased haloperidol
      induced catalepsy in rats but did not have the full efficacy observed with the
      nonselective mAChR antagonist scopolamine. These results suggest that the M1
      receptor participates in the overall regulation of basal ganglia function and
      antiparkinsonian effects of mAChR antagonists but that other mAChR subtype(s)
      also play important roles at multiple levels of the basal ganglia motor circuit.

PMID- 22135384
TI  - The selective M1 muscarinic cholinergic agonist CDD-0102A enhances working memory
      and cognitive flexibility.
AB  - Various neurodegenerative diseases and psychiatric disorders are marked by
      alterations in brain cholinergic function and cognitive deficits. Efforts to
      alleviate such deficits have been limited by a lack of selective M(1) muscarinic
      agonists. 5-(3-Ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine
      hydrochloride (CDD-0102A) is a partial agonist at M(1) muscarinic receptors with
      limited activity at other muscarinic receptor subtypes. The present studies
      investigated the effects of CDD-0102A on working memory and strategy shifting in
      rats. CDD-0102A administered intraperitoneally 30 min before testing at 0.1, 0.3,
      and 1 mg/kg significantly enhanced delayed spontaneous alternation performance in
      a four-arm cross maze, suggesting improvement in working memory. In separate
      experiments, CDD-0102A had potent enhancing effects on learning and switching
      between a place and visual cue discrimination. Treatment with CDD-0102A did not
      affect acquisition of either a place or visual cue discrimination. In contrast,
      CDD-0102A at 0.03 and 0.1 mg/kg significantly enhanced a shift between a place
      and visual cue discrimination. Analysis of the errors in the shift to the place
      or shift to the visual cue strategy revealed that in both cases CDD-0102A
      significantly increased the ability to initially inhibit a previously relevant
      strategy and maintain a new, relevant strategy once selected. In anesthetized
      rats, the minimum dose required to induce salivation was approximately 0.3 mg/kg
      i.p. Salivation increased with dose, and the estimated ED(50) was 2.0 mg/kg. The
      data suggest that CDD-0102A has unique memory and cognitive enhancing properties
      that might be useful in the treatment of neurological disorders at doses that do
      not produce adverse effects such as salivation.

PMID- 22135385
TI  - The 719Arg variant of KIF6 and cardiovascular outcomes in statin-treated, stable
      coronary patients of the treating to new targets and incremental decrease in end
      points through aggressive lipid-lowering prospective studies.
AB  - BACKGROUND: Carriers of the KIF6 719Arg variant may be at increased risk for CVD
      and may benefit more from statin therapy, in terms of CVD risk reduction, than
      noncarriers. Our objective was to investigate whether carriers of the KIF6 719Arg
      genetic variant (rs20455) are at increased cardiovascular risk and obtain more
      benefit from high-dose statin therapy than do noncarriers. METHODS AND RESULTS:
      We used an adjusted Cox proportional hazard model to assess the hazard ratio (HR)
      for the reduction of major cardiovascular events by 80 mg/d atorvastatin over 10
      mg/d atorvastatin in 4599 patients of the Treating to New Targets (TNT) study and
      by 80 mg/d atorvastatin over 20-40 mg/d simvastatin in 6541 patients of the
      Incremental Decrease in End Points Through Aggressive Lipid-Lowering (IDEAL)
      study. A total of 381 and 648 patients had a cardiovascular event during follow
      up in TNT and IDEAL, respectively. Heterozygotes and homozygotes for the minor
      allele were not at increased risk compared with noncarriers. In TNT, for
      noncarriers of the 719Arg allele, the HR for high- versus low-dose atorvastatin
      was 0.81 (95% confidence interval, 0.59-1.11). In carriers of 1 or 2 minor
      alleles, the HR was 0.85 (0.66-1.11) and carriers of 2 copies of the minor allele
      obtained a significant risk reduction (HR: 0.44, 95% confidence interval, 0.23
      0.84). In IDEAL, the respective HRs were 0.85 (0.67-1.10), 0.88 (0.62-1.07) and
      0.91 (0.58-1.43). The interaction term for carrier status by treatment was also
      nonsignificant (P=0.810 in TNT and P=0.909 in IDEAL). CONCLUSIONS: In these 2
      large, randomized clinical trials, carriers of the KIF6 719Arg allele were not at
      increased cardiovascular risk and did not obtain consistent cardiovascular
      benefit from high-dose statin therapy compared with noncarriers.

PMID- 22135388
TI  - Introduction: the Centers for Disease Control and Prevention's Epi-Aids--a fond
      recollection.
AB  - The Epidemic Intelligence Service (EIS) has served the United States and the
      world for >58 years by being an extraordinary apprenticeship in the fundamentals
      of practical field epidemiology: a training program, a professional entry point,
      the basis for lifelong careers, and a closely supervised and mentored opportunity
      for research, analysis, and community service. Epidemic-assistance
      investigations, a key element of the EIS experience, are the written summaries of
      each field investigation undertaken by the EIS officer. The resulting reports
      enter the record of the Centers for Disease Control and Prevention (CDC), provide
      scientific feedback to the state and locality where the epidemic or health
      problem occurred, and often form the basis for a subsequent manuscript to be
      submitted to a peer-reviewed medical journal. The EIS Program was created in 1951
      to be a defense against potential bioterrorism, serve the immediate needs for
      field investigation, and provide for future workforce demands by combining
      epidemiology and laboratory science. During the past 60 years, CDC and public
      health practitioners have broadened their areas of responsibility by adding
      programs in reproductive health, environmental health, chronic diseases,
      nutrition, injury control and prevention, and noncommunicable disease risk
      factors. Epidemic-assistance investigations have evolved similarly. The papers in
      this Journal supplement reflect the evolution of public health responsibilities
      and the growth and development of CDC. They are a testimony to the value of
      clear, concise information and analysis, communicated to those who need to know
      as a public health and societal good.

PMID- 22135386
TI  - Excess of rare variants in non-genome-wide association study candidate genes in
      patients with hypertriglyceridemia.
AB  - BACKGROUND: Rare variant accumulation studies can implicate genes in disease
      susceptibility when a significant burden is observed in patients versus control
      subjects. Such analyses might be particularly useful for candidate genes that are
      selected based on experiments other than genome-wide association studies (GWAS).
      We sought to determine whether rare variants in non-GWAS candidate genes
      identified from mouse models and human mendelian syndromes of
      hypertriglyceridemia (HTG) accumulate in patients with polygenic adult-onset HTG.
      METHODS AND RESULTS: We resequenced protein coding regions of 3 genes with
      established roles (APOC2, GPIHBP1, LMF1) and 2 genes recently implicated (CREB3L3
      and ZHX3) in TG metabolism. We identified 41 distinct heterozygous rare variants,
      including 29 singleton variants, in the combined sample; in total, we observed 47
      rare variants in 413 HTG patients versus 16 in 324 control subjects (odds
      ratio=2.3; P=0.0050). Post hoc assessment of genetic burden in individual genes
      using 3 different tests suggested that the genetic burden was most prominent in
      the established genes LMF1 and APOC2, and also in the recently identified CREB3L3
      gene. CONCLUSIONS: These extensive resequencing studies show a significant
      accumulation of rare genetic variants in non-GWAS candidate genes among patients
      with polygenic HTG, and indicate the importance of testing specific hypotheses in
      large-scale resequencing studies.

PMID- 22135389
TI  - Afterword.
AB  - In 1949, Alexander Langmuir became the first chief epidemiologist at the
      Communicable Disease Center (CDC) in Atlanta, Georgia. Among his many
      contributions to the agency and to public health, 2 of the most important--the
      Epidemic Intelligence Service (EIS) and his particular brand of epidemic
      assistance investigation (the Epi-Aid)--are highlighted in this supplement to the
      American Journal of Epidemiology. What makes these and many other of Langmuir's
      innovations so remarkable is their continued relevance to the health challenges
      we face in this new century. CDC (now the Centers for Disease Control and
      Prevention) is recognized globally for its quality science, not only in
      epidemiology and laboratory practice but also in the behavioral and social
      sciences, statistics, and economics. Support to state and local health
      departments has been instrumental to CDC's success during its first 60 years, and
      the articles describing Epi-Aids in this supplement capture this partnership
      elegantly. They also reflect the evolution of CDC from an agency focused almost
      entirely on communicable diseases to one engaged in a broad array of global
      public health challenges.

PMID- 22135390
TI  - Vaccine-preventable diseases, immunizations, and the Epidemic Intelligence
      Service.
AB  - During 1946-2005, vaccine-preventable diseases were the topic of approximately
      20% of all epidemic-assistance investigations by the Centers for Disease Control
      and Prevention. Both in the United States and abroad, current and former Epidemic
      Intelligence Service officers have played a critical role in describing the
      epidemiology of vaccine-preventable diseases, contributing to development of
      immunization policies, participating in the implementation of immunization
      programs, and establishing effective means for assessing adverse events following
      immunization. As newer vaccines are developed and introduced, they will continue
      to play similar roles and most likely will be involved increasingly in
      investigations of the factors that affect people's willingness to accept
      vaccination for themselves or their children.

PMID- 22135391
TI  - Overview of the impact of epidemic-assistance investigations of foodborne and
      other enteric disease outbreaks, 1946-2005.
AB  - Epidemic-assistance investigations (Epi-Aids) in response to outbreaks of
      foodborne and other enteric pathogens have identified novel pathogens, clinical
      syndromes, and sequelae; described new reservoirs and vehicles of transmission;
      evaluated existing prevention strategies; and identified deficiencies in the food
      safety systems on local, national, and international levels. Since the first Epi
      Aid was issued in 1946, approximately 23% (1,023 of 4,484 for which
      investigations were initiated) of all Epi-Aids have been related to foodborne or
      other enteric diseases. Epi-Aid results have yielded valuable insights into the
      epidemiology of these pathogens and have molded prevention strategies for
      detecting, responding to, and preventing future outbreaks. New challenges,
      brought about in part by centralization and globalization of the food supply,
      will continue to emerge. The need for Epi-Aids of such outbreaks undoubtedly will
      persist as an integral part of future public health response efforts, prevention
      strategies, and training programs.

PMID- 22135392
TI  - Epidemic Intelligence Service investigations of respiratory illness, 1946-2005.
AB  - Infectious respiratory pathogens were the suspected cause of 480 outbreaks
      investigated by the Centers for Disease Control and Prevention's Epidemic
      Intelligence Service officers during 1946-2005. All epidemic-assistance
      investigation reports and associated articles from scientific journals were
      reviewed. Investigations identified 25 different infectious respiratory pathogens
      including, most frequently, tuberculosis, influenza, and legionellosis. Other
      bacterial-, viral-, and fungal-related pathogens also were identified. Epidemic
      assistance investigations were notable for first identifying Legionnaires disease
      and Pontiac fever, hantavirus pulmonary syndrome, and new strains of human and
      avian influenza, as well as emerging challenges (e.g., multidrug-resistant
      tuberculosis and pneumococcus). The investigations provided clinical insights
      into such diseases as pulmonary anthrax and identified high risks of serious
      respiratory illnesses for persons infected with human immunodeficiency virus,
      other immunocompromised persons, and persons with diabetes. They identified
      settings placing persons at high risk of acquiring disease, including nursing
      homes, prisons, homeless shelters, and hospitals. Travel also placed persons at
      risk. Key environmental factors related to spread of diseases and occupational
      risks for brucellosis and psittacosis were identified. The outbreak
      investigations constitute a wealth of prevention experience and provide the basis
      for recommendations to mitigate outbreaks and reduce future risks.

PMID- 22135393
TI  - Epidemic assistance by the Centers for Disease Control and Prevention: role of
      the Epidemic Intelligence Service, 1946-2005.
AB  - Since 1946, the Centers for Disease Control and Prevention has responded to
      urgent requests from US states, federal agencies, and international organizations
      through epidemic-assistance investigations (Epi-Aids). The authors describe the
      first 60 years of Epi-Aids, breadth of problems addressed, evolution of
      methodologies, scope of activities, and impact of investigations on population
      health. They reviewed Epi-Aid reports and EIS Bulletins, contacted current and
      former Epidemic Intelligence Service staff, and systematically searched the
      PubMed and Web of Science databases. They abstracted information on dates,
      location, staff involved, health problems, methods, and impacts of investigations
      according to a preplanned protocol. They assessed the methods presented as well
      as the quality of reports. During 1946-2005, a total of 4,484 investigations of
      health events were initiated by 2,815 Epidemic Intelligence Service officers. In
      the early years, the majority were in response to infectious agents, although
      environmental problems emerged. Investigations in subsequent years focused on
      occupational conditions, birth defects, reproductive health, tobacco use, cancer,
      violence, legal debate, and terrorism. These Epi-Aids heralded expansion of the
      agency's mission and presented new methods in statistics and epidemiology.
      Recommendations from Epi-Aids led to policy implementation, evaluation, or
      modification. Epi-Aids provide the Centers for Disease Control and Prevention
      with the agility to respond rapidly to public health crises.

PMID- 22135394
TI  - Health care-associated infection outbreak investigations by the Centers for
      Disease Control and Prevention, 1946-2005.
AB  - Since 1946, Centers for Disease Control and Prevention (CDC) personnel have
      investigated outbreaks of infections and adverse events associated with delivery
      of health care. CDC Epidemic Intelligence Service officers have led onsite
      investigations of these outbreaks by systematically applying epidemiology,
      statistics, and laboratory science. During 1946-2005, CDC Epidemic Intelligence
      Service officers conducted 531 outbreak investigations in facilities across the
      United States and abroad. Initially, the majority of outbreaks involved
      gastrointestinal tract infections; however, in later years, bloodstream,
      respiratory tract, and surgical wound infections predominated. Among pathogens
      implicated in CDC outbreak investigations, Staphylococcus aureus, Enterococcus
      species, Enterobacteriaceae, nonfermentative Gram-negative bacteria, or yeasts
      predominated, but unusual organisms (e.g., the atypical mycobacteria) were often
      included. Outbreak types varied and often were linked to transfer of colonized
      patients or health care personnel between facilities (multihospital outbreaks),
      national distribution of contaminated products, use of invasive medical devices,
      or variances in practices and procedures in health care environments (e.g.,
      intensive care units, water reservoirs, or hemodialysis units). Through
      partnerships with health care facilities and local and state health departments,
      outbreaks were terminated and lives saved. Data from investigations invariably
      contributed to CDC-generated guidelines for prevention and control of health care
      associated infections.

PMID- 22135395
TI  - Environmental- and injury-related epidemic-assistance investigations, 1946-2005.
AB  - This paper summarizes environmental investigations (n = 458) conducted during the
      first 60 years of the epidemic-assistance investigation program at the Centers
      for Disease Control and Prevention. These investigations were grouped into 10
      categories: toxic chemicals (n = 102), indoor air quality and outdoor air toxics
      (n = 21), new or rare epidemic diseases and unexplained syndromes (n = 29),
      natural disasters (n = 81), terrorism and unintentional human-made disasters (n =
      9), substance use and abuse (n = 13), environmental aspects of infectious disease
      (n = 132), those affecting neonates and infants (n = 11), violence and injuries
      (n = 51), and miscellaneous (n = 9). Among the most important or prominent were
      studies of lead and arsenic toxicity at smelters, mercury in paint and beauty
      creams, dioxin in waste oil in Missouri, polychlorinated biphenyls and multiple
      other toxic chemicals, global pesticide poisoning outbreaks, hepatic angiosarcoma
      among vinyl chloride workers, toxic oil syndrome in Spain, eosinophilia-myalgia
      syndrome from contaminated L-tryptophan, diethylene glycol poisoning in Haiti,
      aflatoxicosis in Kenya, Gulf War illness among veterans, impact and needs
      assessments during natural disasters (e.g., Hurricane Katrina (2005) and the
      Mount St. Helens volcano eruptions (1980)), risk factors for heat-related
      mortality, domestic and international terrorist attacks, Parkinsonism related to
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in California, and unintentional
      injury- and violence-related events.

PMID- 22135396
TI  - Maternal and child health epidemic-assistance investigations, 1946-2005.
AB  - In this article, the authors focus on epidemic-assistance investigations that
      dealt with maternal and child health problems, including unintended and
      adolescent pregnancy and family planning; international reproductive health
      surveys among refugees; pregnancy outcomes, including abortion, maternal
      mortality, infant mortality, and birth defects; leukemia; and Reye syndrome.
      During 1946-2005, a total of 1,969 investigations had sufficient data to classify
      them as possibly related to maternal and child health and were characterized by
      distinctive periods. Those related to family planning, pregnancy intention, and
      reproductive health among refugees began in the early 1970s and continued through
      2005. Abortion-related investigations occurred during 1971-1982. Investigations
      of non-abortion-related maternal morbidity and mortality began in 1979 and
      included 2 international epidemic-assistance investigations. Investigations of
      clusters of disease among infants began in the 1960s, with a special focus on
      Reye syndrome during 1964-1984. Investigations of childhood cancer and birth
      defects began in the late 1950s. The Centers for Disease Control and Prevention
      has used the epidemic-assistance investigations mechanism to respond to a wide
      range of health concerns of women and children. The investigations of abortion
      related health problems might have had the best-documented impact on public
      policy and public health.

PMID- 22135397
TI  - Epidemic assistance from the Centers for Disease Control and Prevention involving
      American Indians and Alaska Natives, 1946-2005.
AB  - The authors describe 169 Centers for Disease Control and Prevention epidemic
      assistance investigations involving American Indians and Alaska Natives that
      occurred during 1946-2005. The unique relation between the US federal government
      and American Indian and Alaska Native tribes is described in the context of
      transfer in the 1950s of responsibility for Indian health to the US Public Health
      Service, which at the time included the Communicable Disease Center, the Centers
      for Disease Control and Prevention's precursor. The vast majority of epidemic
      assistance investigations were for infectious disease outbreaks (86%), with a
      relatively limited number, since 1980 only, involving environmental exposures and
      chronic disease. Although outbreaks investigated were often widespread
      geographically, the majority were limited in scope, typically involving fewer
      than 100 patients. Epidemic-assistance investigations for hepatitis A,
      gastrointestinal and foodborne infectious diseases, vaccine-preventable diseases,
      zoonotic and vectorborne diseases, acute respiratory tract infections,
      environmental exposures, and chronic diseases are described chronologically in
      more detail.

PMID- 22135398
TI  - Fifty-five years of international epidemic-assistance investigations conducted by
      CDC's disease detectives.
AB  - For more than 60 years, the Centers for Disease Control and Prevention (CDC) has
      used its scientific expertise to help people throughout the world live healthier,
      safer, longer lives through science-based health action. In 1951, CDC officially
      established the Epidemic Intelligence Service to help build public health
      capacity. During 1950-2005, CDC's Epidemic Intelligence Service officers
      conducted 462 international epidemiologic field investigations in 131 foreign
      countries and 7 territories. Investigations have included responding to emerging
      infectious and noninfectious disease outbreaks, assisting in disaster response,
      and evaluating core components of public health programs worldwide. Approximately
      81% of investigations were responses to infectious disease outbreaks, but the
      proportion of investigations related to chronic and other noninfectious
      conditions increased 7-fold (6%-45%). These investigations have contributed to
      detecting and characterizing new pathogens (e.g., severe acute respiratory
      syndrome-associated coronavirus) and conditions, provided insights regarding
      factors that cause or contribute to disease acquisition (e.g., Ebola hemorrhagic
      fever), led to development of new diagnostics and surveillance technologies, and
      provided information upon which global health policies and regulations can be
      based. CDC's disease detectives will undoubtedly continue to play a critical role
      in global health and in responding to emerging global disease threats.

PMID- 22135399
TI  - Association between diffuse myocardial fibrosis by cardiac magnetic resonance
      contrast-enhanced T1 mapping and subclinical myocardial dysfunction in diabetic
      patients: a pilot study.
AB  - BACKGROUND: Diabetic patients have increased interstitial myocardial fibrosis on
      histological examination. Magnetic resonance imaging (MRI) T(1) mapping is a
      previously validated imaging technique that can quantify the burden of global and
      regional interstitial fibrosis. However, the association between MRI T(1) mapping
      and subtle left ventricular (LV) dysfunction in diabetic patients is unknown.
      METHODS AND RESULTS: Fifty diabetic patients with normal LV ejection fraction
      (EF) and no underlying coronary artery disease or regional macroscopic scar on
      MRI delayed enhancement were prospectively recruited. Diabetic patients were
      compared with 19 healthy controls who were frequency matched in age, sex and body
      mass index. There were no significant differences in mean LV end-diastolic volume
      index, end-systolic volume index and LVEF between diabetic patients and healthy
      controls. Diabetic patients had significantly shorter global contrast-enhanced
      myocardial T(1) time (425+/-72 ms vs. 504+/-34 ms, P<0.001). There was no
      correlation between global contrast-enhanced myocardial T(1) time and LVEF
      (r=0.14, P=0.32) in the diabetic patients. However, there was good correlation
      between global contrast-enhanced myocardial T(1) time and global longitudinal
      strain (r=-0.73, P<0.001). Global contrast-enhanced myocardial T(1) time was the
      strongest independent determinant of global longitudinal strain on multivariate
      analysis (standardized beta=-0.626, P<0.001). Similarly, there was good
      correlation between global contrast-enhanced myocardial T(1) time and septal E'
      (r=0.54, P<0.001). Global contrast-enhanced myocardial T(1) time was also the
      strongest independent determinant of septal E' (standardized beta=0.432,
      P<0.001). CONCLUSIONS: A shorter global contrast-enhanced myocardial T(1) time
      was associated with more impaired longitudinal myocardial systolic and diastolic
      function in diabetic patients.

PMID- 22135400
TI  - Molecular imaging of mesenchymal stem cell: mechanistic insight into cardiac
      repair after experimental myocardial infarction.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) can differentiate into endothelial
      cells in vivo. However, it is unknown if the differentiated MSCs persist in vivo
      and if this potential persistence contributes to functional improvement after
      experimental myocardial infarction. METHODS AND RESULTS: We generated a
      lentivector encoding 2 distinct reporter genes, one driven by a constitutive
      murine stem cell virus promoter and the other driven by an endothelial-specific
      Tie-2 promoter. The endothelial specificity of the lentivector was validated by
      its expression in endothelial cells but not in human MSCs (hMSCs). The lentivirus
      transduced hMSCs were injected into peri-infarct areas of the hearts of severe
      combined immune-deficient mice. Persistence of injected cells was tracked by
      bioluminescence imaging (BLI) and verified by immunohistochemical staining. The
      BLI signal from the endothelial-specific reporter revealed that hMSCs
      differentiated into endothelial cells 48 hours after injection. However, both the
      constitutive and endothelial-specific BLI signals disappeared by day 50.
      Nonetheless, the improvement in left ventricle ejection fraction with hMSC
      therapy persisted for up to 6 months. Immunohistochemical staining showed that
      hMSC-derived endothelial cells integrated into endogenous CD31(+) vessels.
      Furthermore, hMSC-transplanted hearts had more CD31(+) vessels and a lesser
      degree of cardiac fibrosis compared with the controls at 6 months. CONCLUSIONS:
      hMSCs differentiated into endothelial cells and integrated into blood vessels
      after experimental myocardial infarction. The differentiated hMSCs only lasted
      for up to 50 days in vivo, but improvement in cardiac function persisted for up
      to 6 months. Increased angiogenesis and decreased fibrosis were associated with
      cardiac functional improvement after hMSC transplantation.

PMID- 22135401
TI  - Intermediate-signal-intensity late gadolinium enhancement predicts ventricular
      tachyarrhythmias in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: In hypertrophic cardiomyopathy (HCM), the arrhythmic potential
      associated with a variety of left ventricular myocardial signal intensities
      evident on contrast-enhanced cardiovascular magnetic resonance with late
      gadolinium enhancement (LGE) is unresolved. METHODS AND RESULTS: In 145 HCM
      patients (43+/-15 years old), visually identified areas of LGE in left ventricle
      were analyzed quantitatively for intermediate (>=4 but <6 SD) and high (>=6 SD
      above the mean signal intensity of normal myocardium) LGE signal intensity (LGE
      SI). Ambulatory Holter ECGs were obtained within 7.8+/-8.3 weeks of
      cardiovascular magnetic resonance. HCM patients with nonsustained ventricular
      tachycardia, ventricular couplets, and premature ventricular contractions showed
      greater amounts of intermediate LGE-SI (17+/-7 versus 10+/-10 g, 16+/-10 versus
      10+/-11 g, and 13+/-8 versus 10+/-13 g, respectively; P=0.003 to <0.001) and
      greater amounts of high LGE-SI (15+/-6 versus 10+/-8 g, 14+/-9 versus 10+/-12 g,
      and 12+/-7 versus 10+/-8 g, respectively; P=0.02-0.003) than patients without
      these arrhythmias. In HCM patients with either nonsustained ventricular
      tachycardia, couplets, or premature ventricular contractions, the extent of
      intermediate LGE-SI exceeded that of high LGE-SI (17+/-7 versus 15+/-6 g, 16+/-10
      versus 14+/-9 g, and 13+/-8 versus 12+/-7 g, respectively; P=0.01-0.04). In
      addition, the receiver operating characteristic area under the curve established
      intermediate LGE-SI as a better discriminator of patients with nonsustained
      ventricular tachycardia than was high LGE-SI, with 7 additional patients with
      this arrhythmia identified. CONCLUSIONS: In patients with HCM, intermediate LGE
      SI is a better predictor of ventricular tachyarrhythmias (including nonsustained
      ventricular tachycardia, a risk factor for sudden death) than is high LGE-SI.
      Longitudinal studies in larger HCM cohorts are justified to define the
      independent prognostic impact of intermediate LGE-SI.

PMID- 22135402
TI  - Akt1-mediated skeletal muscle growth attenuates cardiac dysfunction and
      remodeling after experimental myocardial infarction.
AB  - BACKGROUND: It is appreciated that aerobic endurance exercise can attenuate
      unfavorable myocardial remodeling following myocardial infarction. In contrast,
      little is known about the effects of increasing skeletal muscle mass, typically
      achieved through resistance training, on this process. Here, we utilized
      transgenic (TG) mice that can induce the growth of functional skeletal muscle by
      switching Akt1 signaling in muscle fibers to assess the impact of glycolytic
      muscle growth on post-myocardial infarction cardiac remodeling. METHODS AND
      RESULTS: Male-noninduced TG mice and their nontransgenic littermates (control)
      were subjected to left anterior coronary artery ligation. Two days after surgery,
      mice were provided doxycycline in their drinking water to activate Akt1 transgene
      expression in a skeletal muscle-specific manner. Myogenic Akt1 activation led to
      diminished left ventricular dilation and reduced contractile dysfunction compared
      with control mice. Improved cardiac function in Akt1 TG mice was coupled to
      diminished myocyte hypertrophy, decreased interstitial fibrosis, and increased
      capillary density. ELISA and protein array analyses demonstrated that serum
      levels of proangiogenic growth factors were upregulated in Akt1 TG mice compared
      with control mice. Cardiac eNOS was activated in Akt1 TG mice after myocardial
      infarction. The protective effect of skeletal muscle Akt activation on cardiac
      remodeling and systolic function was abolished by treatment with the eNOS
      inhibitor l-NAME. CONCLUSIONS: Akt1-mediated skeletal muscle growth attenuates
      cardiac remodeling after myocardial infarction and is associated with an
      increased capillary density in the heart. This improvement appears to be mediated
      by skeletal muscle to cardiac communication, leading to activation of eNOS
      signaling in the heart.

PMID- 22135403
TI  - Differential expression of PDE5 in failing and nonfailing human myocardium.
AB  - BACKGROUND: Recognizing that inhibitors of phosphodiesterase type 5 (PDE5) are
      increasingly employed in patients with pulmonary hypertension and right
      ventricular (RV) failure, we examined PDE5 expression in the human RV and its
      impact on myocardial contractility. METHODS AND RESULTS: Tissue extracts from the
      RV of 20 patients were assayed for PDE5 expression using immunoblot and
      immunohistochemical staining. Tissues were selected from groups of nonfailing
      organ donors and transplant recipients with endstage ischemic cardiomyopathy or
      idiopathic dilated cardiomyopathy. Among dilated cardiomyopathy patients,
      subgroups with mild or severe RV dysfunction and prior left ventricular assist
      devices were analyzed separately. Our results showed that PDE5 abundance
      increased more than 4-fold in the RVs of the ischemic cardiomyopathy compared
      with the nonfailing group. In dilated cardiomyopathy, PDE5 upregulation was more
      moderate and varied with the severity of RV dysfunction. Immunohistochemical
      staining confirmed that cardiac myocytes contributed to the upregulation in the
      failing hearts. In functional studies, PDE5 inhibition produced little change in
      developed force in RV trabeculae from nonfailing hearts but produced a moderate
      increase in RV trabeculae from failing hearts. CONCLUSIONS: Our results showed
      the etiology- and severity-dependent upregulation of myocyte PDE5 expression in
      the RV and the impact of this upregulation on myocardial contractility. These
      findings suggest that RV PDE5 expression could contribute to the pathogenesis of
      RV failure, and direct myocardial responses to PDE5 inhibition may modulate the
      indirect responses mediated by RV afterload reduction.

PMID- 22135404
TI  - Etsrp/Etv2 is directly regulated by Foxc1a/b in the zebrafish angioblast.
AB  - RATIONALE: Endothelial cells are developmentally derived from angioblasts
      specified in the mesodermal germ cell layer. The transcription factor etsrp/etv2
      is at the top of the known genetic hierarchy for angioblast development. The
      transcriptional events that induce etsrp expression and angioblast specification
      are not well understood. OBJECTIVE: We generated etsrp:gfp transgenic zebrafish
      and used them to identify regulatory regions and transcription factors critical
      for etsrp expression and angioblast specification from mesoderm. METHODS AND
      RESULTS: To investigate the mechanisms that initiate angioblast cell
      transcription during embryogenesis, we have performed promoter analysis of the
      etsrp locus in zebrafish. We describe three enhancer elements sufficient for
      endothelial gene expression when place in front of a heterologous promoter. The
      deletion of all 3 regulatory regions led to a near complete loss of endothelial
      expression from the etsrp promoter. One of the enhancers, located 2.3 kb upstream
      of etsrp contains a consensus FOX binding site that binds Foxc1a and Foxc1b in
      vitro by EMSA and in vivo using ChIP. Combined knockdown of foxc1a/b, using
      morpholinos, led to a significant decrease in etsrp expression at early
      developmental stages as measured by quantitative reverse transcriptase-polymerase
      chain reaction and in situ hybridization. Decreased expression of primitive
      erythrocyte genes scl and gata1 was also observed, whereas pronephric gene pax2a
      was relatively normal in expression level and pattern. CONCLUSIONS: These
      findings identify mesodermal foxc1a/b as a direct upstream regulator of etsrp in
      angioblasts. This establishes a new molecular link in the process of mesoderm
      specification into angioblast.

PMID- 22135408
TI  - Bifidobacteria and subsets of dendritic cells: friendly players in immune
      regulation!

PMID- 22135405
TI  - Genome-wide analysis of retrogene polymorphisms in Drosophila melanogaster.
AB  - Gene duplication via retrotransposition has been shown to be an important
      mechanism in evolution, affecting gene dosage and allowing for the acquisition of
      new gene functions. Although fixed retrotransposed genes have been found in a
      variety of species, very little effort has been made to identify retrogene
      polymorphisms. Here, we examine 37 Illumina-sequenced North American Drosophila
      melanogaster inbred lines and present the first ever data set and analysis of
      polymorphic retrogenes in Drosophila. We show that this type of polymorphism is
      quite common, with any two gametes in the North American population differing in
      the presence or absence of six retrogenes, accounting for ~13% of gene copy
      number heterozygosity. These retrogenes were identified by a straightforward
      method that can be applied using any type of DNA sequencing data. We also use a
      variant of this method to conduct a genome-wide scan for intron presence/absence
      polymorphisms, and show that any two chromosomes in the population likely differ
      in the presence of multiple introns. We show that these polymorphisms are all in
      fact deletions rather than intron gain events present in the reference genome.
      Finally, by leveraging the known location of the parental genes that give rise to
      the retrogene polymorphisms, we provide direct evidence that natural selection is
      responsible for the excess of fixations of retrogenes moving off of the X
      chromosome in Drosophila. Further efforts to identify retrogene and intron
      presence/absence polymorphisms will undoubtedly improve our understanding of the
      evolution of gene copy number and gene structure.

PMID- 22135409
TI  - Tendon vibration does not alter decreased responsiveness of motoneurones in the
      absence of motor cortical input during fatigue.

PMID- 22135410
TI  - Human hand function: the limitations of brain and brawn.

PMID- 22135411
TI  - Cartilage quality, overweight and osteoarthritis: a case for new behaviour?

PMID- 22135414
TI  - Disparities in child access to emergency care for acute oral injury.

PMID- 22135412
TI  - Weight loss in obese people has structure-modifying effects on medial but not on
      lateral knee articular cartilage.
AB  - BACKGROUND: Obesity is an important risk factor for knee osteoarthritis (OA),
      Weight loss can reduce the symptoms of knee OA. No prospective studies assessing
      the impact of weight loss on knee cartilage structure and composition have been
      performed. OBJECTIVES: To assess the impact of weight loss on knee cartilage
      thickness and composition. METHODS: 111 obese adults were recruited from either
      laparoscopic adjustable gastric banding or exercise and diet weight loss
      programmes from two tertiary centres. MRI was performed at baseline and 12-month
      follow-up to assess cartilage thickness. 78 eligible subjects also underwent
      delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), an estimate of
      proteoglycan content. The associations between cartilage outcomes (cartilage
      thickness and dGEMRIC index) and weight loss were adjusted for age, gender, body
      mass index (BMI) and presence of clinical knee OA. RESULTS: Mean age was 51.7 +/-
      11.8 years and mean BMI was 36.6 +/- 5.8 kg/m(2); 32% had clinical knee OA. Mean
      weight loss was 9.3 +/- 11.9%. Percentage weight loss was negatively associated
      with cartilage thickness loss in the medial femoral compartment in multiple
      regression analysis (beta=0.006, r(2)=0.19, p=0.029). This association was not
      detected in the lateral compartment (r(2)=0.12, p=0.745). Percentage weight loss
      was associated with an increase in medial dGEMRIC in multiple regression analysis
      (beta=3.9, r(2)=0.26; p=0.008) but not the lateral compartment (r(2)=0.14,
      p=0.34). For every 10% weight loss there was a gain in the medial dGEMRIC index
      of 39 ms (r(2)=0.28; p=0.014). The lowest weight loss cut-off associated with
      reduced medial femoral cartilage thickness loss and improved medial dGEMRIC index
      was 7%. CONCLUSIONS: Weight loss is associated with improvements in the quality
      (increased proteoglycan content) and quantity (reduced cartilage thickness
      losses) of medial articular cartilage. This was not observed in the lateral
      compartment. This could ultimately lead to a reduced need for total joint
      replacements and is thus a finding with important public health implications.

PMID- 22135415
TI  - Care of an infant with lethal malformation: where do we draw the line?

PMID- 22135416
TI  - Which species is it? Species-driven gene name disambiguation using random walks
      over a mixture of adjacency matrices.
AB  - MOTIVATION: The scientific literature contains a wealth of information about
      biological systems. Manual curation lacks the scalability to extract this
      information due to the ever-increasing numbers of papers being published. The
      development and application of text mining technologies has been proposed as a
      way of dealing with this problem. However, the inter-species ambiguity of the
      genomic nomenclature makes mapping of gene mentions identified in text to their
      corresponding Entrez gene identifiers an extremely difficult task. We propose a
      novel method, which transforms a MEDLINE record into a mixture of adjacency
      matrices; by performing a random walkover the resulting graph, we can perform
      multi-class supervised classification allowing the assignment of taxonomy
      identifiers to individual gene mentions. The ability to achieve good performance
      at this task has a direct impact on the performance of normalizing gene mentions
      to Entrez gene identifiers. Such graph mixtures add flexibility and allow us to
      generate probabilistic classification schemes that naturally reflect the
      uncertainties inherent, even in literature-derived data. RESULTS: Our method
      performs well in terms of both micro- and macro-averaged performance, achieving
      micro-F(1) of 0.76 and macro-F(1) of 0.36 on the publicly available DECA corpus.
      Re-curation of the DECA corpus was performed, with our method achieving 0.88
      micro-F(1) and 0.51 macro-F(1). Our method improves over standard classification
      techniques [such as support vector machines (SVMs)] in a number of ways:
      flexibility, interpretability and its resistance to the effects of class bias in
      the training data. Good performance is achieved without the need for
      computationally expensive parse tree generation or 'bag of words classification'.

PMID- 22135417
TI  - SNPxGE(2): a database for human SNP-coexpression associations.
AB  - MOTIVATION: Recently, gene-coexpression relationships have been found to be often
      conditional and dynamic. Many studies have suggested that single nucleotide
      polymorphisms (SNPs) have impacts on gene expression variations in human
      populations. RESULTS: The SNPxGE(2) database contains the computationally
      predicted human SNP-coexpression associations, i.e. the differential coexpression
      between two genes is associated with the genotypes of an SNP. These data were
      generated from a large-scale association study that was based on the HapMap phase
      I data, which covered 269 individuals from 4 human populations, 556 873 SNPs and
      15 000 gene expression profiles. In order to reduce the computational cost, the
      SNP-coexpression associations were assessed using gap/substitution models, proven
      to have a comparable power to logistic regression models. The results, at a false
      discovery rate (FDR) cutoff of 0.1, consisted of 44 769 and 50 792 SNP
      coexpression associations based on single and pooled populations, respectively,
      and can be queried in the SNPxGE(2) database via either gene symbol or reference
      SNP ID. For each reported association, a detailed information page is provided.
      AVAILABILITY: http://lambchop.ads.uga.edu/snpxge2/index.php CONTACT:
      wyp1125@uga.edu, rrekaya@uga.edu.

PMID- 22135419
TI  - DMAN: a Java tool for analysis of multi-well differential scanning fluorimetry
      experiments.
AB  - SUMMARY: Differential scanning fluorimetry (DSF) is a rapid technique that can be
      used in structural biology to study protein-ligand interactions. We have
      developed DMAN, a novel tool to analyse multi-well plate data obtained in DSF
      experiments. DMAN is easy to install and provides a user-friendly interface.
      Multi-well plate layouts can be designed by the user and experimental data can be
      annotated and analysed by DMAN according to the specified plate layout.
      Statistical tests for significance are performed automatically, and graphical
      tools are also provided to assist in data analysis. The modular concept of this
      software will allow easy development of other multi-well plate analysis
      applications in the future. AVAILABILITY AND IMPLEMENTATION: DMAN is implemented
      in Java to provide a cross-platform compatibility. It is freely available to
      academic users at http://www.structuralchemistry.org/pcsb/. To download DMAN,
      users will be asked for their name, institution and email address. A manual can
      also be downloaded from this site. CONTACT: conan.wang@griffith.edu.au;
      a.hofmann@griffith.edu.au.

PMID- 22135421
TI  - Eating disorders.

PMID- 22135418
TI  - Metscape 2 bioinformatics tool for the analysis and visualization of metabolomics
      and gene expression data.
AB  - MOTIVATION: Metabolomics is a rapidly evolving field that holds promise to
      provide insights into genotype-phenotype relationships in cancers, diabetes and
      other complex diseases. One of the major informatics challenges is providing
      tools that link metabolite data with other types of high-throughput molecular
      data (e.g. transcriptomics, proteomics), and incorporate prior knowledge of
      pathways and molecular interactions. RESULTS: We describe a new, substantially
      redesigned version of our tool Metscape that allows users to enter experimental
      data for metabolites, genes and pathways and display them in the context of
      relevant metabolic networks. Metscape 2 uses an internal relational database that
      integrates data from KEGG and EHMN databases. The new version of the tool allows
      users to identify enriched pathways from expression profiling data, build and
      analyze the networks of genes and metabolites, and visualize changes in the
      gene/metabolite data. We demonstrate the applications of Metscape to annotate
      molecular pathways for human and mouse metabolites implicated in the pathogenesis
      of sepsis-induced acute lung injury, for the analysis of gene expression and
      metabolite data from pancreatic ductal adenocarcinoma, and for identification of
      the candidate metabolites involved in cancer and inflammation. AVAILABILITY:
      Metscape is part of the National Institutes of Health-supported National Center
      for Integrative Biomedical Informatics (NCIBI) suite of tools, freely available
      at http://metscape.ncibi.org. It can be downloaded from http://cytoscape.org or
      installed via Cytoscape plugin manager. CONTACT: metscape-help@umich.edu;
      akarnovs@umich.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 22135422
TI  - Staphylococcal infections in the era of MRSA.

PMID- 22135423
TI  - Developmental milestones 3: social-emotional development.

PMID- 22135424
TI  - Focus on diagnosis: congenital infections (TORCH).

PMID- 22135425
TI  - Index of suspicion. Case 1: pallor, screaming, sweating, and breathing difficulty
      associated with feeding in a 2-month-old infant. Case 2: Swelling, redness,
      warmth, tenderness, and purulent drainage under the nail in an adolescent girl.
      Case 3: urticarial rash, fatigue, achiness, and dark urine in an adolescent girl.

PMID- 22135426
TI  - Methanol ingestion.

PMID- 22135427
TI  - Visual diagnosis: a 7-month-old who has a persistent rash.

PMID- 22135428
TI  - Question from the clinician: management of prenatal hydronephrosis.

PMID- 22135429
TI  - Hybrid incompatibility in Arabidopsis is determined by a multiple-locus genetic
      network.
AB  - The cross between Arabidopsis thaliana and the closely related species
      Arabidopsis arenosa results in postzygotic hybrid incompatibility, manifested as
      seed death. Ecotypes of A. thaliana were tested for their ability to produce live
      seed when crossed to A. arenosa. The identified genetic variation was used to map
      quantitative trait loci (QTLs) encoded by the A. thaliana genome that affect the
      frequency of postzygotic lethality and the phenotypes of surviving seeds. Seven
      QTLs affecting the A. thaliana component of this hybrid incompatibility were
      identified by crossing a Columbia * C24 recombinant inbred line population to
      diploid A. arenosa pollen donors. Additional epistatic loci were identified based
      on their pairwise interaction with one or several of these QTLs. Epistatic
      interactions were detected for all seven QTLs. The two largest additive QTLs were
      subjected to fine-mapping, indicating the action of at least two genes in each.
      The topology of this network reveals a large set of minor-effect loci from the
      maternal genome controlling hybrid growth and viability at different
      developmental stages. Our study establishes a framework that will enable the
      identification and characterization of genes and pathways in A. thaliana
      responsible for hybrid lethality in the A. thaliana * A. arenosa interspecific
      cross.

PMID- 22135430
TI  - Control of starch granule numbers in Arabidopsis chloroplasts.
AB  - The aim of this work was to investigate starch granule numbers in Arabidopsis
      (Arabidopsis thaliana) leaves. Lack of quantitative information on the extent of
      genetic, temporal, developmental, and environmental variation in granule numbers
      is an important limitation in understanding control of starch degradation and the
      mechanism of granule initiation. Two methods were developed for reliable
      estimation of numbers of granules per chloroplast. First, direct measurements
      were made on large series of consecutive sections of mesophyll tissue obtained by
      focused ion beam-scanning electron microscopy. Second, average numbers were
      calculated from the starch contents of leaves and chloroplasts and estimates of
      granule mass based on granule dimensions. Examination of wild-type plants and
      accumulation and regulation of chloroplast (arc) mutants with few, large
      chloroplasts provided the following new insights. There is wide variation in
      chloroplast volumes in cells of wild-type leaves. Granule numbers per chloroplast
      are correlated with chloroplast volume, i.e. large chloroplasts have more
      granules than small chloroplasts. Mature leaves of wild-type plants and arc
      mutants have approximately the same number of granules per unit volume of stroma,
      regardless of the size and number of chloroplasts per cell. Granule numbers per
      unit volume of stroma are also relatively constant in immature leaves but are
      greater than in mature leaves. Granule initiation occurs as chloroplasts divide
      in immature leaves, but relatively little initiation occurs in mature leaves.
      Changes in leaf starch content over the diurnal cycle are largely brought about
      by changes in the volume of a fixed number of granules.

PMID- 22135432
TI  - Editorial policies aimed at improving the transparency and validity of published
      research.

PMID- 22135431
TI  - Genetic architecture of maize kernel composition in the nested association
      mapping and inbred association panels.
AB  - The maize (Zea mays) kernel plays a critical role in feeding humans and livestock
      around the world and in a wide array of industrial applications. An understanding
      of the regulation of kernel starch, protein, and oil is needed in order to
      manipulate composition to meet future needs. We conducted joint-linkage
      quantitative trait locus mapping and genome-wide association studies (GWAS) for
      kernel starch, protein, and oil in the maize nested association mapping
      population, composed of 25 recombinant inbred line families derived from diverse
      inbred lines. Joint-linkage mapping revealed that the genetic architecture of
      kernel composition traits is controlled by 21-26 quantitative trait loci.
      Numerous GWAS associations were detected, including several oil and starch
      associations in acyl-CoA:diacylglycerol acyltransferase1-2, a gene that regulates
      oil composition and quantity. Results from nested association mapping were
      verified in a 282 inbred association panel using both GWAS and candidate gene
      association approaches. We identified many beneficial alleles that will be useful
      for improving kernel starch, protein, and oil content.

PMID- 22135433
TI  - Cannabis use and cognitive dysfunction.

PMID- 22135434
TI  - "Blues" ain't good for the heart.

PMID- 22135435
TI  - Repackaging mental health programs in low- and middle-income countries.

PMID- 22135436
TI  - Closing the treatment gap.

PMID- 22135438
TI  - Catatonia from its creation to DSM-V: Considerations for ICD.
AB  - Catatonia was delineated only as a type of schizophrenia in the many American
      Psychiatric Association DSM classifications and revisions from 1952 until 1994
      when "catatonia secondary to a medical condition" was added. Since the 1970s the
      diagnosis of catatonia has been clarified as a syndrome of rigidity, posturing,
      mutism, negativism, and other motor signs of acute onset. It is found in about
      10% of psychiatric hospital admissions, in patients with depressed and manic mood
      states and in toxic states. It is quickly treatable to remission by
      benzodiazepines and by ECT. The DSM-V revision proposes catatonia in two major
      diagnostic classes, specifiers for 10 principal diagnoses, and deletion of the
      designation of schizophrenia, catatonic type. This complex recommendation serves
      no clinical or research purpose and confuses treatment options. Catatonia is best
      considered in the proposed ICD revision as a unique syndrome of multiple forms
      warranting a single unique defined class similar to that of delirium.

PMID- 22135439
TI  - Development and validation of the Domestic Violence Questionnaire in married
      women aged 18-55 years.
AB  - BACKGROUND: Intimate partner violence against women is seen in all cultures. It
      has wide-ranging effects on the physical and psychological health of women. In
      the local language, available questionnaires are either too exhaustive or
      inadequate to assess domestic violence comprehensively. OBJECTIVE: To develop a
      Domestic Violence Questionnaire in Malayalam and validate it for married women
      aged 18-55 years in the local population. STUDY DESIGN: Descriptive study -
      Validation of questionnaire. MATERIALS AND METHODS: A 29-item questionnaire, to
      identify domestic violence over the past 1 year, was developed in the local
      language, by selecting items from two other questionnaires and based on expert
      opinion. Item reduction was done after pilot testing. Then, this 25-item
      questionnaire was administered to 276 married women aged 18-55 years. Reliability
      and validity were estimated. Factor analysis was done for item reduction. Poor
      loading, wrong-loading and cross-loading items were removed from the
      questionnaire. Taking the subjective perception of the participants regarding
      themselves experiencing domestic violence as the gold standard, a Receiver
      Operator Characteristic curve was drawn to decide the cut-off score with optimum
      sensitivity and specificity. RESULTS: The final questionnaire had 20 items - 13
      items for psychological and 7 items for physical violence. Internal consistency
      reliability was 0.92. At a cut-off score of 5, sensitivity was 89.5% and
      specificity 87.2%. CONCLUSIONS: The Domestic Violence Questionnaire in Malayalam
      has adequate psychometric properties to identify intimate partner violence
      against women in the local population.

PMID- 22135437
TI  - State of Consultation-Liaison Psychiatry in India: Current status and vision for
      future.
AB  - Over the years Consultation-Liaison (C-L) psychiatry has contributed
      significantly to the growth of the psychiatry and has brought psychiatry very
      close to the advances in the medicine. It has also led to changes in the medical
      education and in the providing comprehensive management to the physically ill. In
      India, although the General Hospital Psychiatric units were established in 1930s,
      C-L Psychiatry has never been the main focus of training and research. Hence
      there is an urgent need to improve C-L Psychiatry services and training to
      provide best and optimal care to the patients and provide best education to the
      trainees.

PMID- 22135440
TI  - The development of a guideline and its impact on the media reporting of suicide.
AB  - CONTEXT: A causal association between media reporting of suicides and the
      subsequent actual suicides has been observed. There are no studies from India
      regarding media reporting of suicide. This study examines whether educating media
      professionals about responsible reporting of suicides can change the quality of
      reporting. AIMS: To study the impact of a guideline on the reporting style of
      suicides by journalists. SETTINGS AND DESIGN: Newspaper reports in the local
      language examined by psychiatrists. MATERIALS AND METHODS: The Department of
      Psychiatry of a Teaching Hospital conducted a workshop for journalists, with the
      collaboration of media and mental health professionals and came out with a
      guideline about responsible reporting of suicide. Using this, a proforma was
      designed for assessing newspaper reports of suicides. All the suicide reports in
      the leading newspapers in Kerala were analyzed for one year prior to the
      workshop, the immediate next year, the second year, and six years later, using
      the 15 item proforma and whether each report was concordant or discordant to each
      item in the proforma was noted. RESULTS: The total concordant responses were
      43.7% in the year prior to the workshop, 45.2% during the first year following
      the workshop, 46.2% in the next year, and 45.7% after six years. When the trend
      of each item was examined, the concordance rates were increasing in each item,
      except two. There was no statistical significance. CONCLUSIONS: A workshop for
      journalists could bring about positive changes in the media reporting of
      suicides. The changes persisted over the years, although they did not reach
      statistical significance.

PMID- 22135441
TI  - Indian experiences with International Classification of Mental and Behaviour
      Disorders-10: Pathway for ICD-11.
AB  - BACKGROUND: International Classification of Mental and Behavioural Disorders
      (ICD)-10 has been serving its purpose in the spheres of diagnosing psychiatric
      patients, research, and education since long. With ICD-11 is on the horizon, this
      is the right time to assess issues in the application of these guidelines in
      routine clinical practice. AIM: In this study, an effort was made to find out day
      to-day difficulties in application of ICD-10. MATERIALS AND METHODS: A total of
      130 patients attending for the first time the outpatient Department of
      Psychiatry, CSMMU, Lucknow, were taken as sample for the present study. The
      "provisional diagnosis", which was made after the usual assessments on a single
      day at the clinical setting was recorded. The selected patients were later
      assessed in detail and a "final diagnosis was recorded for these patients. The
      diagnoses were matched with ICD-10 and rated on a five-point scale. STATISTICS:
      The direct count and percentage analysis was done. RESULTS: Results show that
      67.69% "provisional diagnosis" were fully matched, while 8% and 5% diagnosis had
      no match and some match, respectively with the "final diagnosis". There were also
      some cases that had significant match (1.5%) and almost match (17.69%).
      CONCLUSION: In a busy clinical setting, the focus of the clinicians is more on
      management and accurate diagnosis based on ICD-10 may be ignored.

PMID- 22135442
TI  - Help-seeking behavior of patients with mental health problems visiting a tertiary
      care center in north India.
AB  - BACKGROUND: Patients with mental health problems in the nonwestern world seek
      help from a variety of sources, such as the family physicians, psychiatrists,
      psychologists, traditional faith-healers, or alternative medicine practitioners.
      Understanding the help-seeking behavior is important from the public health
      perspective. MATERIALS AND METHODS: Two hundred new patients visiting a
      psychiatric outpatient service at a tertiary care hospital were interviewed on a
      semi-structured questionnaire for various services contacted by them for their
      mental health problems. RESULTS: Psychiatrists were the first choice in 45% of
      the cases followed by nonpsychiatric physicians and religious faith healers.
      Important reasons to seek help from different sources included easy
      accessibility, belief in the system, or particular healer and good reputation.
      Mean duration of treatment varied from 2.35 months with the alternative system
      practitioners to 16.63 months with the psychiatrists. The mean expenditure per
      visit to a service was highest for the nonpsychiatric physician and lowest for
      alternative system practitioners. CONCLUSION: Patients with mental health
      problems seek help from psychiatrists, nonpsychiatric physicians, faith healers,
      alternative system practitioners, and traditional faith healers for multiple
      reasons. It is important to sensitize various nonpsychiatric physicians with
      early identification and optimum management of mental disorders.

PMID- 22135443
TI  - Development of a murine animal model of depression for repeated dosing with human
      interferon alpha.
AB  - BACKGROUND: Neuropsychiatric adverse effects of interferon (IFN) alpha are well
      known. There is little clinically relevant research on animal models of
      depression with recombinant human IFN alpha 2b (rhIFN-alpha2b). AIM: To identify
      an appropriate dose and duration of administration of recombinant human
      interferon alpha-2b (rhIFN-alpha2b) to establish a convenient and clinically
      relevant murine model of chronic rhIFN-alpha2b-induced depression using the
      forced swim test (FST). MATERIALS AND METHODS: Using a 4*3 factorial design,
      rhIFN-alpha2b was administered subcutaneously to mice (n=180) in the dose range
      of 400, 800, and 1600 IU/g/day for 5, 10, and 15 days; saline-treated mice formed
      the control groups. In each group, 1 day after the last dose, the mice were
      assessed for immobility in the FST. In another experiment, at these same doses
      and time points, the effect of rhIFN-alpha2b on murine motility was assessed in
      the small open field. RESULTS: We found that rhIFN-alpha2b significantly
      increased immobility in the FST. The immobility was detectable by day 5 and did
      not increase with duration of IFN treatment. The immobility was apparent with the
      400 IU/g/day dose and was not greater at higher IFN doses. At no dose or time
      point did rhIFN-alpha2b alter murine motility in the small open field.
      CONCLUSION: We conclude that rhIFN-alpha2b-induced behavioral despair,
      represented by immobility in the FST, is not due to reduced basal motility. The
      FST may therefore be used as a convenient Swiss albino mouse model of chronic
      rhIFN-alpha2b-induced depression with a 400-1600 IU/g/day dose administered
      subcutaneously for 5-15 days. The most economical model is 400 IU/g/day
      administered for 5 days.

PMID- 22135444
TI  - Intervention for suicide attempters: A randomized controlled study.
AB  - AIM: To determine whether brief intervention and contact (BIC) is effective in
      reducing subsequent suicidal behavior among suicide attempters. MATERIALS AND
      METHODS: Suicide attempters (n=680) admitted in a general hospital in Chennai
      were randomly allocated to treatment as usual and BIC whose components include
      brief intervention at the time of discharge and contact for 18 months. RESULTS:
      Completed suicide was significantly lower in the BIC group, OR 35.4 (CI 18.4 -
      78.2) as also attempted suicide, OR 17.3 (CI 10.8 - 29.7). CONCLUSIONS: This low
      cost intervention which can be readily implemented may be an important suicide
      prevention strategy in healthcare settings in India.

PMID- 22135445
TI  - Changes in intellectual and academic performance of children following computer
      based training: Preliminary results.
AB  - BACKGROUND: The aim of this pilot study was to assess the effectiveness of a
      computer-based intervention on children who were average in academic performance.
      MATERIALS AND METHODS: Twenty-one children aged between 8 and 11 years, in
      classes 3(rd), 4(th) or 5(th) formed the sample with 12 in the experimental (who
      underwent the computer-based training) and 9 in the control group (who did not
      undergo the training). Pre- and post-assessment was done for all children using a
      battery of intelligence tests, and the marks obtained by the child at school. The
      difference in performance of the two groups was compared using the t test.
      RESULT: There was significant improvement within the performance of the
      experimental group in cognitive functioning (P<0.05) and school marks (P<0.05),
      as compared with the children in the control group. The limitations of the study
      include the small sample size, non-random allocation to groups and the (pre and
      post) assessments being carried out by the researcher. However, the trend of
      results is promising. CONCLUSION: Thus, a brief computer-aided intervention for
      improving neuropsychological functions such as attention and working memory has
      had a positive impact on the cognitive and academic skills of children who were
      average in scholastic performance.

PMID- 22135446
TI  - Psychiatric morbidity in prisoners.
AB  - CONTEXT: The prevalence of psychiatric illness in correctional settings is
      significantly elevated, with higher than community rates reported for most mental
      disorders. AIMS: (1) To examine the socio-demographic profile of convicted
      prisoners. (2) To evaluate the prevalence of psychiatric disorders in convicted
      prisoners. MATERIALS AND METHODS: 500 convicts were assessed for psychiatric
      morbidity with the help of (a) Socio-demographic proforma, (b) Pareek Udai and
      Trivedi G's socio-economic status scale (rural) (household schedule), (c)
      Kuppuswamy's economic status scale (urban) and (d) Present State Examination
      (PSE). RESULTS: 23.8% of the convicted prisoners were suffering from psychiatric
      illness excluding substance abuse. 56.4% of the prisoners had history of
      substance abuse / dependence prior to incarceration. CONCLUSIONS: The results
      suggest that a substantial burden of psychiatric morbidity exists in the prison
      population of India and the burden of psychiatric illness in this vulnerable and
      marginalized population poses a serious challenge to psychiatrists.

PMID- 22135447
TI  - Psychiatry movie club: A novel way to teach psychiatry.
AB  - For decades, films across the world have entertained people and affected their
      attitudes regarding certain issues and conditions. Documentary films have been
      used by governments in different parts of the world to educate the general public
      and promote health and prevent the spread of disease as part of public health
      programs. Psychiatry as a branch of medicine like the rest of medicine continues
      to develop. With an increasing awareness among the general population and
      popularity of films showing various aspects of mental illnesses on the rise,
      educators and teachers are turning their attention to using films for education
      of medical students and psychiatric trainees. Although films may be stereotypical
      and prejudiced, they can be used successfully in teaching psychiatry trainees. In
      this paper, development of a movie club and its use are described and suggestions
      made to improve the use of films in this process.

PMID- 22135448
TI  - National mental health programme: Manpower development scheme of eleventh five
      year plan.
AB  - Mental disorders impose a massive burden in the society. The National Mental
      Health Programme (NMHP) is being implemented by the Government of India to
      support state governments in providing mental health services in the country.
      India is facing shortage of qualified mental health manpower for District Mental
      Health Programme (DMHP) in particular and for the whole mental health sector in
      general. Recognizing this key constraint Government of India has formulated
      manpower development schemes under NMHP to address this issue. Under the scheme
      11 centers of excellence in mental health, 120 PG departments in mental health
      specialties, upgradation of psychiatric wings of medical colleges, modernization
      of state-run mental hospitals will be supported. The expected outcome of the
      Manpower Development schemes is 104 psychiatrists, 416 clinical psychologists,
      416 PSWs and 820 psychiatric nurses annually once these institutes/ departments
      are established. Together with other components such as DMHP with added services,
      Information, education and communication activities, NGO component, dedicated
      monitoring mechanism, research and training, this scheme has the potential to
      make a facelift of the mental health sector in the country which is essentially
      dependent on the availability and equitable distribution mental health manpower
      in the country.

PMID- 22135449
TI  - Delusion of polygamy in proxy: An addition in delusional procreation syndrome.
AB  - The content of a delusion is of special interest to mental health professional
      and is still expanding. The concept of delusional procreation syndrome (DPS),
      containing delusions in all possible sequential steps in procreation, has been
      recently proposed. The authors report the case of a married woman harboring a
      delusion that her husband has been having 10 wives (ie, married once every year
      in last 10 years) and, as an extension to that, of having two children from each
      wife. The authors name this as "delusion of polygamy in proxy," and describe it
      as another dimension of DPS.

PMID- 22135450
TI  - Anterior capsulotomy for refractory OCD: First case as per the core group
      guidelines.
AB  - Obsessive-compulsive disorder (OCD) is a psychiatric disease characterized by
      anxiety-provoking thoughts (obsessions) leading to repeated, time-consuming
      behaviors (compulsions) that may or may not provide temporary relief. With an
      approximate prevalence of 2-3% of the general population and 0.6% in the Indian
      population, OCD is a debilitating disorder that can significantly affect nearly
      every aspect of a patient's life, and in some cases, lead to suicide.

PMID- 22135451
TI  - Prayer, randomized controlled trials and distance healing: A response to Dr.
      Jana.

PMID- 22135452
TI  - Clozapine: A friend estranged?

PMID- 22135453
TI  - Penfield - A great explorer of psyche-soma-neuroscience.

PMID- 22135454
TI  - Neuronal and molecular substrates for optimal foraging in Caenorhabditis elegans.
AB  - Variation in food quality and abundance requires animals to decide whether to
      stay on a poor food patch or leave in search of better food. An important
      question in behavioral ecology asks when is it optimal for an animal to leave a
      food patch it is depleting. Although optimal foraging is central to evolutionary
      success, the neural and molecular mechanisms underlying it are poorly understood.
      Here we investigate the neuronal basis for adaptive food-leaving behavior in
      response to resource depletion in Caenorhabditis elegans, and identify several of
      the signaling pathways involved. The ASE neurons, previously implicated in salt
      chemoattraction, promote food-leaving behavior via a cGMP pathway as food becomes
      limited. High ambient O(2) promotes food-leaving via the O(2)-sensing neurons
      AQR, PQR, and URX. Ectopic activation of these neurons using channelrhodopsin is
      sufficient to induce high food-leaving behavior. In contrast, the neuropeptide
      receptor NPR-1, which regulates social behavior on food, acts in the ASE neurons,
      the nociceptive ASH neurons, and in the RMG interneuron to repress food-leaving.
      Finally, we show that neuroendocrine signaling by TGF-beta/DAF-7 and neuronal
      insulin signaling are necessary for adaptive food-leaving behavior. We suggest
      that animals integrate information about their nutritional state with ambient
      oxygen and gustatory stimuli to formulate optimal foraging strategies.

PMID- 22135457
TI  - Gating of the MlotiK1 potassium channel involves large rearrangements of the
      cyclic nucleotide-binding domains.
AB  - Cyclic nucleotide-regulated ion channels are present in bacteria, plants,
      vertebrates, and humans. In higher organisms, they are closely involved in
      signaling networks of vision and olfaction. Binding of cAMP or cGMP favors the
      activation of these ion channels. Despite a wealth of structural and studies,
      there is a lack of structural data describing the gating process in a full-length
      cyclic nucleotide-regulated channel. We used high-resolution atomic force
      microscopy (AFM) to directly observe the conformational change of the membrane
      embedded bacterial cyclic nucleotide-regulated channel MlotiK1. In the nucleotide
      bound conformation, the cytoplasmic cyclic nucleotide-binding (CNB) domains of
      MlotiK1 are disposed in a fourfold symmetric arrangement forming a pore-like
      vestibule. Upon nucleotide-unbinding, the four CNB domains undergo a large
      rearrangement, stand up by ~1.7 nm, and adopt a structurally variable grouped
      conformation that closes the cytoplasmic vestibule. This fully reversible
      conformational change provides insight into how CNB domains rearrange when
      regulating the potassium channel.

PMID- 22135456
TI  - The inflammatory cytokine IL-18 induces self-reactive innate antibody responses
      regulated by natural killer T cells.
AB  - Inflammatory responses initiate rapid production of IL-1 family cytokines,
      including IL-18. This cytokine is produced at high levels in inflammatory
      diseases, including allergy and autoimmunity, and is known to induce IgE
      production in mice. Here we provide evidence that IL-18 is directly coupled to
      induction of self-reactive IgM and IgG antibody responses and recruitment of
      innate B2 B cells residing in the marginal zone of the spleen. Moreover, the data
      suggest that the B-cell activation occurs predominantly in splenic
      extrafollicular plasma cell foci and is regulated by natural killer T (NKT) cells
      that prevent formation of mature germinal centers. We also find evidence that NKT
      cells control this type of B-cell activation via cytotoxicity mediated by both
      the perforin and CD95/CD178 pathways. Thus, NKT cells regulate innate antibody
      responses initiated by an inflammatory stimulus, suggesting a general mechanism
      that regulates B-cell behavior in inflammation and autoreactivity.

PMID- 22135458
TI  - Contribution of a mutational bias in hepatitis C virus replication to the genetic
      barrier in the development of drug resistance.
AB  - The development of resistance to direct-acting antivirals (DAAs) targeting the
      hepatitis C virus (HCV) can compromise therapy. However, mechanisms that
      determine prevalence and frequency of resistance-conferring mutations remain
      elusive. Here, we studied the fidelity of the HCV RNA-dependent RNA polymerase
      NS5B in an attempt to link the efficiency of mismatch formation with genotypic
      changes observed in vivo. Enzyme kinetic measurements revealed unexpectedly high
      error rates (approximately 10(-3) per site) for G:U/U:G mismatches. The strong
      preference for G:U/U:G mismatches over all other mistakes correlates with a
      mutational bias in favor of transitions over transversions. Deep sequencing of
      HCV RNA samples isolated from 20 treatment-naive patients revealed an
      approximately 75-fold difference in frequencies of the two classes of mutations.
      A stochastic model based on these results suggests that the bias toward
      transitions can also affect the selection of resistance-conferring mutations.
      Collectively, the data provide strong evidence to suggest that the nature of the
      nucleotide change can contribute to the genetic barrier in the development of
      resistance to DAAs.

PMID- 22135459
TI  - Functional reconstitution of human eukaryotic translation initiation factor 3
      (eIF3).
AB  - Protein fate in higher eukaryotes is controlled by three complexes that share
      conserved architectural elements: the proteasome, COP9 signalosome, and
      eukaryotic translation initiation factor 3 (eIF3). Here we reconstitute the 13
      subunit human eIF3 in Escherichia coli, revealing its structural core to be the
      eight subunits with conserved orthologues in the proteasome lid complex and COP9
      signalosome. This structural core in eIF3 binds to the small (40S) ribosomal
      subunit, to translation initiation factors involved in mRNA cap-dependent
      initiation, and to the hepatitis C viral (HCV) internal ribosome entry site
      (IRES) RNA. Addition of the remaining eIF3 subunits enables reconstituted eIF3 to
      assemble intact initiation complexes with the HCV IRES. Negative-stain EM
      reconstructions of reconstituted eIF3 further reveal how the approximately 400
      kDa molecular mass structural core organizes the highly flexible 800 kDa
      molecular mass eIF3 complex, and mediates translation initiation.

PMID- 22135460
TI  - Crystal structure of the bacteriophage T4 late-transcription coactivator gp33
      with the beta-subunit flap domain of Escherichia coli RNA polymerase.
AB  - Activated transcription of the bacteriophage T4 late genes, which is coupled to
      concurrent DNA replication, is accomplished by an initiation complex containing
      the host RNA polymerase associated with two phage-encoded proteins, gp55 (the
      basal promoter specificity factor) and gp33 (the coactivator), as well as the DNA
      mounted sliding-clamp processivity factor of the phage T4 replisome (gp45, the
      activator). We have determined the 3.0 A-resolution X-ray crystal structure of
      gp33 complexed with its RNA polymerase binding determinant, the beta-flap domain.
      Like domain 4 of the promoter specificity sigma factor (sigma(4)), gp33 interacts
      with RNA polymerase primarily by clamping onto the helix at the tip of the beta
      flap domain. Nevertheless, gp33 and sigma(4) are not structurally related. The
      gp33/beta-flap structure, combined with biochemical, biophysical, and structural
      information, allows us to generate a structural model of the T4 late promoter
      initiation complex. The model predicts protein/protein interactions within the
      complex that explain the presence of conserved patches of surface-exposed
      residues on gp33, and provides a structural framework for interpreting and
      designing future experiments to functionally characterize the complex.

PMID- 22135461
TI  - Sparse linear modeling of next-generation mRNA sequencing (RNA-Seq) data for
      isoform discovery and abundance estimation.
AB  - Since the inception of next-generation mRNA sequencing (RNA-Seq) technology,
      various attempts have been made to utilize RNA-Seq data in assembling full-length
      mRNA isoforms de novo and estimating abundance of isoforms. However, for genes
      with more than a few exons, the problem tends to be challenging and often
      involves identifiability issues in statistical modeling. We have developed a
      statistical method called "sparse linear modeling of RNA-Seq data for isoform
      discovery and abundance estimation" (SLIDE) that takes exon boundaries and RNA
      Seq data as input to discern the set of mRNA isoforms that are most likely to
      present in an RNA-Seq sample. SLIDE is based on a linear model with a design
      matrix that models the sampling probability of RNA-Seq reads from different mRNA
      isoforms. To tackle the model unidentifiability issue, SLIDE uses a modified
      Lasso procedure for parameter estimation. Compared with deterministic isoform
      assembly algorithms (e.g., Cufflinks), SLIDE considers the stochastic aspects of
      RNA-Seq reads in exons from different isoforms and thus has increased power in
      detecting more novel isoforms. Another advantage of SLIDE is its flexibility of
      incorporating other transcriptomic data such as RACE, CAGE, and EST into its
      model to further increase isoform discovery accuracy. SLIDE can also work
      downstream of other RNA-Seq assembly algorithms to integrate newly discovered
      genes and exons. Besides isoform discovery, SLIDE sequentially uses the same
      linear model to estimate the abundance of discovered isoforms. Simulation and
      real data studies show that SLIDE performs as well as or better than major
      competitors in both isoform discovery and abundance estimation. The SLIDE
      software package is available at
      https://sites.google.com/site/jingyijli/SLIDE.zip.

PMID- 22135462
TI  - Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle
      cells.
AB  - Soft-tissue sarcomas are heterogeneous cancers that can present with tissue
      specific differentiation markers. To examine the cellular basis for this
      histopathological variation and to identify sarcoma-relevant molecular pathways,
      we generated a chimeric mouse model in which sarcoma-associated genetic lesions
      can be introduced into discrete, muscle-resident myogenic and mesenchymal cell
      lineages. Expression of Kirsten rat sarcoma viral oncogene [Kras(G12V)] and
      disruption of cyclin-dependent kinase inhibitor 2A (CDKN2A; p16p19) in
      prospectively isolated satellite cells gave rise to pleomorphic rhabdomyosarcomas
      (MyoD-, Myogenin- and Desmin-positive), whereas introduction of the same
      oncogenetic hits in nonmyogenic progenitors induced pleomorphic sarcomas lacking
      myogenic features. Transcriptional profiling demonstrated that myogenic and
      nonmyogenic Kras; p16p19(null) sarcomas recapitulate gene-expression signatures
      of human rhabdomyosarcomas and identified a cluster of genes that is concordantly
      up-regulated in both mouse and human sarcomas. This cluster includes genes
      associated with Ras and mechanistic target of rapamycin (mTOR) signaling, a
      finding consistent with activation of the Ras and mTOR pathways both in Kras;
      p16p19(null) sarcomas and in 26-50% of human rhabdomyosarcomas surveyed.
      Moreover, chemical inhibition of Ras or mTOR signaling arrested the growth of
      mouse Kras; p16p19(null) sarcomas and of human rhabdomyosarcoma cells in vitro
      and in vivo. Taken together, these data demonstrate the critical importance of
      lineage commitment within the tumor cell-of-origin in determining sarcoma
      histotype and introduce an experimental platform for rapid dissection of sarcoma
      relevant cellular and molecular events.

PMID- 22135463
TI  - Genomic anatomy of Escherichia coli O157:H7 outbreaks.
AB  - The rapid emergence of Escherichia coli O157:H7 from an unknown strain in 1982 to
      the dominant hemorrhagic E. coli serotype in the United States and the cause of
      widespread outbreaks of human food-borne illness highlights a need to evaluate
      critically the extent to which genomic plasticity of this important enteric
      pathogen contributes to its pathogenic potential and its evolution as well as its
      adaptation in different ecological niches. Aimed at a better understanding of the
      evolution of the E. coli O157:H7 pathogenome, the present study presents the high
      quality sequencing and comparative phylogenomic analysis of a comprehensive panel
      of 25 E. coli O157:H7 strains associated with three nearly simultaneous food
      borne outbreaks of human disease in the United States. Here we present a
      population genetic analysis of more than 200 related strains recovered from
      patients, contaminated produce, and zoonotic sources. High-resolution
      phylogenomic approaches allow the dynamics of pathogenome evolution to be
      followed at a high level of phylogenetic accuracy and resolution. SNP discovery
      and study of genome architecture and prophage content identified numerous
      biomarkers to assess the extent of genetic diversity within a set of clinical and
      environmental strains. A total of 1,225 SNPs were identified in the present study
      and are now available for typing of the E. coli O157:H7 lineage. These data
      should prove useful for the development of a refined phylogenomic framework for
      forensic, diagnostic, and epidemiological studies to define better risk in
      response to novel and emerging E. coli O157:H7 resistance and virulence
      phenotypes.

PMID- 22135464
TI  - Investment in rapid growth shapes the evolutionary rates of essential proteins.
AB  - Proteins evolve at very different rates and, most notably, at rates inversely
      proportional to the level at which they are produced. The relative frequency of
      highly expressed proteins in the proteome, and thus their impact on the cell
      budget, increases steeply with growth rate. The maximal growth rate is a key life
      history trait reflecting trade-offs between rapid growth and other fitness
      components. We show that the maximal growth rate is weakly affected by genetic
      drift. The negative correlation between protein expression levels and
      evolutionary rate and the positive correlation between expression levels of
      highly expressed proteins and growth rates, suggest that investment in growth
      affects the evolutionary rate of proteins, especially the highly expressed ones.
      Accordingly, analysis of 61 families of orthologs in 74 proteobacteria shows that
      differences in evolutionary rates between lowly and highly expressed proteins
      depend on maximal growth rates. Analyses of complexes with key roles in bacterial
      growth and strikingly different expression levels, the ribosome and the
      replisome, confirm these patterns and suggest that the growth-related sequence
      conservation is associated with protein synthesis. Maximal growth rates also
      shape protein evolution in the other bacterial clades. Long-branch attractions
      associated with this effect might explain why clades with persistent history of
      slow growth are attracted to the root when the tree of prokaryotes is inferred
      using highly, but not lowly, expressed proteins. These results indicate that
      reconstruction of deep phylogenies can be strongly affected by maximal growth
      rates, and highlight the importance of life-history traits and their
      physiological consequences for protein evolution.

PMID- 22135465
TI  - Quantitative differences in CD45 expression unmask functions for CD45 in B-cell
      development, tolerance, and survival.
AB  - The receptor-like tyrosine phosphatase CD45 positively regulates antigen receptor
      signaling by dephosphorylating the inhibitory tyrosine of the src family kinases.
      CD45-deficient mice fail to fully unmask the role of CD45 in B cells because of
      the expression of a partially redundant tyrosine phosphatase, CD148. However,
      mice that are doubly deficient in CD45 and CD148 exhibit a very early block in B
      cell development, thereby obscuring later roles for CD45. To overcome these
      limitations, here we take advantage of an allelic series of mice in which CD45
      expression is titrated broadly (0-180%). Although high expression of CD45
      inhibits T-cell receptor (TCR) signaling, we show that CD45 plays a purely
      positive regulatory role during B-cell receptor (BCR) signaling. In concert with
      exaggerated BCR signaling, increasing CD45 expression drives enhanced receptor
      editing in the bone marrow and profound loss of follicular and marginal zone B
      cells in the spleen. In the context of the IgHEL/sHEL model of B-cell tolerance,
      such high CD45 expression transforms anergy into deletion. Unexpectedly,
      elimination of the autoantigen sHEL in this model system in order to block clonal
      deletion fails to rescue survival of mature B cells. Rather, high CD45 expression
      reduces B-cell activating factor receptor (BAFFR) expression and inhibits B-cell
      activating factor (BAFF)-induced B-cell survival in a cell-intrinsic manner.
      Taken together, our findings reveal how CD45 function diverges in T cells and B
      cells, as well as how autoreactive B cells are censored as they transit
      development.

PMID- 22135466
TI  - Mechanistic modeling of the effects of myoferlin on tumor cell invasion.
AB  - Myoferlin (MYOF) is a member of the evolutionarily conserved ferlin family of
      proteins, noted for their role in a variety of membrane processes, including
      endocytosis, repair, and vesicular transport. Notably, ferlins are implicated in
      Caenorhabditis elegans sperm motility (Fer-1), mammalian skeletal muscle
      development and repair (MYOF and dysferlin), and presynaptic transmission in the
      auditory system (otoferlin). In this paper, we demonstrate that MYOF plays a
      previously unrecognized role in cancer cell invasion, using a combination of
      mathematical modeling and in vitro experiments. Using a real-time impedance-based
      invasion assay (xCELLigence), we have shown that lentiviral-based knockdown of
      MYOF significantly reduced invasion of MDA-MB-231 breast cancer cells in Matrigel
      bioassays. Based on these experimental data, we developed a partial differential
      equation model of MYOF effects on cancer cell invasion, which we used to generate
      mechanistic hypotheses. The mathematical model predictions revealed that matrix
      metalloproteinases (MMPs) may play a key role in modulating this invasive
      property, which was supported by experimental data using quantitative RT-PCR
      screens. These results suggest that MYOF may be a promising target for biomarkers
      or drug target for metastatic cancer diagnosis and therapy, perhaps mediated
      through MMPs.

PMID- 22135467
TI  - Measurement of the ground-state distributions in bistable mechanically
      interlocked molecules using slow scan rate cyclic voltammetry.
AB  - In donor-acceptor mechanically interlocked molecules that exhibit bistability,
      the relative populations of the translational isomers--present, for example, in a
      bistable [2]rotaxane, as well as in a couple of bistable [2]catenanes of the
      donor-acceptor vintage--can be elucidated by slow scan rate cyclic voltammetry.
      The practice of transitioning from a fast scan rate regime to a slow one permits
      the measurement of an intermediate redox couple that is a function of the
      equilibrium that exists between the two translational isomers in the case of all
      three mechanically interlocked molecules investigated. These intermediate redox
      potentials can be used to calculate the ground-state distribution constants, K.
      Whereas, (i) in the case of the bistable [2]rotaxane, composed of a dumbbell
      component containing pi-electron-rich tetrathiafulvalene and dioxynaphthalene
      recognition sites for the ring component (namely, a tetracationic cyclophane,
      containing two pi-electron-deficient bipyridinium units), a value for K of 10 +/-
      2 is calculated, (ii) in the case of the two bistable [2]catenanes--one
      containing a crown ether with tetrathiafulvalene and dioxynaphthalene recognition
      sites for the tetracationic cyclophane, and the other, tetrathiafulvalene and
      butadiyne recognition sites--the values for K are orders (one and three,
      respectively) of magnitude greater. This observation, which has also been probed
      by theoretical calculations, supports the hypothesis that the extra stability of
      one translational isomer over the other is because of the influence of the
      enforced side-on donor-acceptor interactions brought about by both pi-electron
      rich recognition sites being part of a macrocyclic polyether.

PMID- 22135468
TI  - Dynamics of transcriptional start site selection during nitrogen stress-induced
      cell differentiation in Anabaena sp. PCC7120.
AB  - The fixation of atmospheric N(2) by cyanobacteria is a major source of nitrogen
      in the biosphere. In Nostocales, such as Anabaena, this process is spatially
      separated from oxygenic photosynthesis and occurs in heterocysts. Upon nitrogen
      step-down, these specialized cells differentiate from vegetative cells in a
      process controlled by two major regulators: NtcA and HetR. However, the regulon
      controlled by these two factors is only partially defined, and several aspects of
      the differentiation process have remained enigmatic. Using differential RNA-seq,
      we experimentally define a genome-wide map of >10,000 transcriptional start sites
      (TSS) of Anabaena sp. PCC7120, a model organism for the study of prokaryotic cell
      differentiation and N(2) fixation. By analyzing the adaptation to nitrogen
      stress, our global TSS map provides insight into the dynamic changes that modify
      the transcriptional organization at a critical step of the differentiation
      process. We identify >900 TSS with minimum fold change in response to nitrogen
      deficiency of eight. From these TSS, at least 209 were under control of HetR,
      whereas at least 158 other TSS were potentially directly controlled by NtcA. Our
      analysis of the promoters activated during the switch to N(2) fixation adds
      hundreds of protein-coding genes and noncoding transcripts to the list of
      potentially involved factors. These data experimentally define the NtcA regulon
      and the DIF(+) motif, a palindrome at or close to position -35 that seems
      essential for heterocyst-specific expression of certain genes.

PMID- 22135469
TI  - QnAs with Inder M. Verma. Interview by Prashant Nair.

PMID- 22135470
TI  - Galacturonosyltransferase (GAUT)1 and GAUT7 are the core of a plant cell wall
      pectin biosynthetic homogalacturonan:galacturonosyltransferase complex.
AB  - Plant cell wall pectic polysaccharides are arguably the most complex
      carbohydrates in nature. Progress in understanding pectin synthesis has been slow
      due to its complex structure and difficulties in purifying and expressing the low
      abundance, Golgi membrane-bound pectin biosynthetic enzymes. Arabidopsis
      galacturonosyltransferase (GAUT) 1 is an alpha-1,4-galacturonosyltransferase
      (GalAT) that synthesizes homogalacturonan (HG), the most abundant pectic
      polysaccharide. We now show that GAUT1 functions in a protein complex with the
      homologous GAUT7. Surprisingly, although both GAUT1 and GAUT7 are type II
      membrane proteins with single N-terminal transmembrane-spanning domains, the N
      terminal region of GAUT1, including the transmembrane domain, is cleaved in vivo.
      This raises the question of how the processed GAUT1 is retained in the Golgi, the
      site of HG biosynthesis. We show that the anchoring of GAUT1 in the Golgi
      requires association with GAUT7 to form the GAUT1:GAUT7 complex. Proteomics
      analyses also identified 12 additional proteins that immunoprecipitate with the
      GAUT1:GAUT7 complex. This study provides conclusive evidence that the GAUT1:GAUT7
      complex is the catalytic core of an HG:GalAT complex and that cell wall matrix
      polysaccharide biosynthesis occurs via protein complexes. The processing of GAUT1
      to remove its N-terminal transmembrane domain and its anchoring in the Golgi by
      association with GAUT7 provides an example of how specific catalytic domains of
      plant cell wall biosynthetic glycosyltransferases could be assembled into protein
      complexes to enable the synthesis of the complex and developmentally and
      environmentally plastic plant cell wall.

PMID- 22135471
TI  - Rice, fish, and the planet.

PMID- 22135472
TI  - Accurate sampling and deep sequencing of the HIV-1 protease gene using a Primer
      ID.
AB  - Viruses can create complex genetic populations within a host, and deep sequencing
      technologies allow extensive sampling of these populations. Limitations of these
      technologies, however, potentially bias this sampling, particularly when a PCR
      step precedes the sequencing protocol. Typically, an unknown number of templates
      are used in initiating the PCR amplification, and this can lead to unrecognized
      sequence resampling creating apparent homogeneity; also, PCR-mediated
      recombination can disrupt linkage, and differential amplification can skew allele
      frequency. Finally, misincorporation of nucleotides during PCR and errors during
      the sequencing protocol can inflate diversity. We have solved these problems by
      including a random sequence tag in the initial primer such that each template
      receives a unique Primer ID. After sequencing, repeated identification of a
      Primer ID reveals sequence resampling. These resampled sequences are then used to
      create an accurate consensus sequence for each template, correcting for
      recombination, allelic skewing, and misincorporation/sequencing errors. The
      resulting population of consensus sequences directly represents the initial
      sampled templates. We applied this approach to the HIV-1 protease (pro) gene to
      view the distribution of sequence variation of a complex viral population within
      a host. We identified major and minor polymorphisms at coding and noncoding
      positions. In addition, we observed dynamic genetic changes within the population
      during intermittent drug exposure, including the emergence of multiple resistant
      alleles. These results provide an unprecedented view of a complex viral
      population in the absence of PCR resampling.

PMID- 22135473
TI  - More than one dynamic crossover in protein hydration water.
AB  - Studies of liquid water in its supercooled region have helped us better
      understand the structure and behavior of water. Bulk water freezes at its
      homogeneous nucleation temperature (approximately 235 K), but protein hydration
      water avoids this crystallization because each water molecule binds to a protein.
      Here, we study the dynamics of the hydrogen bond (HB) network of a percolating
      layer of water molecules and compare the measurements of a hydrated globular
      protein with the results of a coarse-grained model that successfully reproduces
      the properties of hydration water. Using dielectric spectroscopy, we measure the
      temperature dependence of the relaxation time of proton charge fluctuations.
      These fluctuations are associated with the dynamics of the HB network of water
      molecules adsorbed on the protein surface. Using Monte Carlo simulations and mean
      field calculations, we study the dynamics and thermodynamics of the model. Both
      experimental and model analyses are consistent with the interesting possibility
      of two dynamic crossovers, (i) at approximately 252 K and (ii) at approximately
      181 K. Because the experiments agree with the model, we can relate the two
      crossovers to the presence at ambient pressure of two specific heat maxima. The
      first is caused by fluctuations in the HB formation, and the second, at a lower
      temperature, is due to the cooperative reordering of the HB network.

PMID- 22135474
TI  - Effect of beta-sheet crystalline content on mass transfer in silk films.
AB  - The material properties of silk are favorable for drug delivery due to the
      ability to control material structure and morphology under ambient, aqueous
      processing conditions. Mass transport of compounds with varying physical-chemical
      characteristics was studied in silk fibroin films with control of beta-sheet
      crystalline content. Two compounds, vitamin B12 and fluorescein isothiocynate
      (FITC) labeled lysozyme were studied in a diffusion apparatus to determine
      transport through silk films. The films exhibited size exclusion phenomenon with
      permeability coefficients with contrasting trends with increases in beta-sheet
      crystallinity. The size exclusion phenomenon observed with the two model
      compounds was characterized by contrasting trends in permeability coefficients of
      the films as a function of beta-sheet crystallinity. The diffusivity of the
      compounds was examined in the context of free volume theory. Apart from the beta
      sheet crystallinity, size of the compound and its interactions with silk
      influenced mass transfer. Diffusivity of vitamin B12 was modeled to define a
      power law relationship with beta-sheet crystallinity. The results of the study
      demonstrate that diffusion of therapeutic agents though silk fibroin films can be
      directed to match a desired rate by modulating secondary structure of the silk
      proteins.

PMID- 22135475
TI  - Bayesian Experimental Design for Long-Term Longitudinal HIV Dynamic Studies.
AB  - The study of HIV dynamics is one of the most important developments in recent
      AIDS research for understanding the pathogenesis of HIV-1 infection and antiviral
      treatment strategies. Currently a large number of AIDS clinical trials on HIV
      dynamics are in development worldwide. However, many design issues that arise
      from AIDS clinical trials have not been addressed. In this paper, we use a
      simulation-based approach to deal with design problems in Bayesian hierarchical
      nonlinear (mixed-effects) models. The underlying model characterizes the long
      term viral dynamics with antiretroviral treatment where we directly incorporate
      drug susceptibility and exposure into a function of treatment efficacy. The
      Bayesian design method is investigated under the framework of hierarchical
      Bayesian (mixed-effects) models. We compare a finite number of feasible candidate
      designs numerically, which are currently used in AIDS clinical trials from
      different perspectives, and provide guidance on how a design might be chosen in
      practice.

PMID- 22135476
TI  - Editorial preface to the fourth issue of 2011.

PMID- 22135477
TI  - Abdominal obesity, an independent cardiovascular risk factor in Indian
      subcontinent: A clinico epidemiological evidence summary.
AB  - Evidence is emerging that obesity-associated cardiovascular disorders (CVD) show
      variations across regions and ethnicities. However, it is unclear if there are
      distinctive patterns of abdominal obesity contributing to an increased CVD risk
      in South Asians. Also, potential underlying mechanistic pathways of such unique
      patterns are not comprehensively reported in South Asians. This review sets out
      to examine both. A comprehensive database search strategy was undertaken, namely,
      PubMed, Embase and Cochrane Library, applying specific search terms for
      potentially relevant published literature in English language. Grey literature,
      including scientific meeting abstracts, expert consultations, text books and
      government/non-government publications were also retrieved. South Asians have 3
      5% higher body fat than whites, at any given body mass index. Additional
      distinctive features, such as South Asian phenotype, low adipokine production,
      lower lean body mass, ethno-specific socio-cultural and economic factors, were
      considered as potential contributors to an early age-onset of obesity-linked CVD
      risk in South Asians. Proven cost-effective anti-obesity strategies, including
      the development of ethno-specific clinical risk assessment tools, should be
      adopted early in the life-course to prevent premature CVD deaths and morbidity in
      South Asians.

PMID- 22135478
TI  - Evaluating the role of connexin43 in congenital heart disease: Screening for
      mutations in patients with outflow tract anomalies and the analysis of knock-in
      mouse models.
AB  - BACKGROUND: GJA1 gene encodes a gap junction protein known as connexin 43 (Cx43).
      Cx43 is abundantly expressed in the ventricular myocardium and in cardiac neural
      crest cells. Cx43 is proposed to play an important role in human congenital heart
      disease, as GJA1 knock-out mice die neonatally from outflow tract obstruction. In
      addition, patients with visceroatrial heterotaxia or hypoplastic left heart
      syndrome were reported to have point mutations in GJA1 at residues that affect
      protein kinase phosphorylation and gating of the gap junction channel. However,
      as these clinical findings were not replicated in subsequent studies, the
      question remains about the contribution of GJA1 mutations in human congenital
      heart disease (CHD). MATERIALS AND METHODS: We analyzed the GJA1 coding sequence
      in 300 patients with CHD from two clinical centers, focusing on outflow tract
      anomalies. This included 152 with Tetralogy of Fallot from over 200 patients
      exhibiting outflow tract anomalies, as well as other structural heart defects
      including atrioventricular septal defects and other valvar anomalies. Our
      sequencing analysis revealed only two silent nucleotide substitutions in 8
      patients. To further assess the possible role of Cx43 in CHD, we also generated
      two knock-in mouse models with point mutations at serine residues subject to
      protein kinase C or casein kinase phosphorylation, sites that are known to
      regulate gating and trafficking of Cx43, respectively. RESULTS: Both heterozygous
      and homozygous knock-in mice were long term viable and did not exhibit overt CHD.
      CONCLUSION: The combined clinical and knock-in mouse mutant studies indicate GJA1
      mutation is not likely a major contributor to CHD, especially those involving
      outflow tract anomalies.

PMID- 22135479
TI  - Diastolic dysfunction in asymptomatic type 2 diabetes mellitus with normal
      systolic function.
AB  - BACKGROUND: The incidence of heart failure in diabetic subjects is high even in
      the absence of hypertension and coronary artery disease. AIMS: The purpose of
      this study was to study the incidence of diastolic dysfunction in diabetic
      subjects and its relation to age, duration of diabetes mellitus (DM),
      Glycosylated hemoglobin (HbA1c) levels, obesity indices and diabetic
      microangiopathies. SETTINGS AND DESIGN: This was a case control prospective study
      conducted at the teaching hospital during a one year period. MATERIALS AND
      METHODS: A total of 127 subjects (case) with type 2 diabetes of more than five
      years duration were studied. Total 100 healthy subjects were included as the
      control group. Echocardiography was performed to assess left ventricular
      diastolic function. RESULTS: Out of the total 127 subjects, 69 (54.33%) from the
      case group had diastolic dysfunction, and 11% amongst 100 in the control group
      population showed the diastolic dysfunction (P < 0.001). Patients with a longer
      duration of DM (of 11 to 15 years) had a higher prevalence of diastolic
      dysfunction (P < 0.02). Subjects with high waist circumference and high waist to
      hip ratio had statistically significant diastolic dysfunction with 'P' =0.001 and
      'P' = < 0.02 respectively. Subjects with HbA1c > 7.5% had a higher prevalence of
      diastolic dysfunction than subjects with HbA1c < 7.5% (P < 0.02). Diastolic
      dysfunction was present in majority of the subjects with autonomic neuropathy and
      retinopathy. CONCLUSIONS: Present study reveals high incidence of diastolic
      dysfunction in asymptomatic diabetic; subjects and, this finding was correlated
      with the duration of diabetes, HbA1c levels, obesity indices and diabetic
      microangiopathies. We conclude that early diagnosis and institution of treatment
      will reduce morbidity and improve the outcomes, and prevent future heart failure.

PMID- 22135480
TI  - Effect of yogic bellows on cardiovascular autonomic reactivity.
AB  - CONTEXT: Yoga is an ancient science, which originated in India. Pranayama has
      been assigned a very important role in yogic system of exercises. It is known
      that regular practice of breathing exercises (pranayama) increases
      parasympathetic tone, decreases sympathetic activity, and improves cardiovascular
      functions. Different types of breathing exercises alter autonomic balance for
      good by either decrease in sympathetic or increase in parasympathetic activity.
      Mukh Bhastrika (yogic bellows), a type of pranayama breathing when practiced
      alone, has demonstrated increase in sympathetic activity and load on heart, but
      when practiced along with other types of pranayama has showed improved cardiac
      performance. AIM: The present study was conducted to evaluate the effect of long
      term practice of fast pranayama (Mukh Bhastrika) on autonomic balance on
      individuals with stable cardiac function. SETTINGS AND DESIGN: This
      interventional study was conducted in the department of physiology. MATERIALS AND
      METHODS: 50 healthy male subjects of 18 - 25 years age group, fulfilling the
      inclusion and exclusion criteria underwent Mukh Bhastrika training for 12 weeks.
      Cardiovascular autonomic reactivity tests were performed before and after the
      training. STATISTICAL ANALYSIS USED: The parameters were analyzed by Student t
      test. RESULTS: This study showed an increase in parasympathetic activity i.e.,
      reduced basal heart rate, increase in valsalva ratio and deep breathing
      difference in heart rate; and reduction in sympathetic activity i.e., reduction
      in fall of systolic blood pressure on posture variation. CONCLUSION: It can be
      concluded that Mukh Bhastrika has beneficial effect on cardiac autonomic
      reactivity, if practiced for a longer duration.

PMID- 22135482
TI  - Cardio-pulmonary fitness test by ultra-short heart rate variability.
AB  - OBJECTIVES: It is known that exercise induces cardio-respiratory autonomic
      modulation. The aim of this study was to assess the cardio-pulmonary fitness by
      ultra-short heart rate variability. MATERIALS AND METHODS: Study population was
      divided into 3 groups: Group-1 (n = 40) consisted of military sports man. Group-2
      (n = 40) were healthy age-matched sedentary male subjects with normal body mass
      index [BMI = 19 - 25 kg/m(2)). Group-3 (n = 40) were healthy age-matched obese
      male subjects [BMI > 29 kg/m(2)). Standard deviation of normal-to-normal QRS
      intervals (SDNN) was recorded over 15 minutes. Bruce protocol treadmill test was
      used; and, maximum oxygen consumption (VO(2)max) was calculated. RESULTS: WHEN
      THE STUDY POPULATION WAS DIVIDED INTO QUARTILES OF SDNN (FIRST QUARTILE: < 60
      msec; second quartile: > 60 and < 100 msec; third quartile: > 100 and <140 msec;
      and fourth quartile: >140 msec), progressive increase was found in VO(2)max; and,
      SDNN was significantly linked with estimated VO(2)max. CONCLUSION: In conclusion,
      the results of this study demonstrate that exercise training improves cardio
      respiratory autonomic function (and increases heart rate variability).
      Improvement in cardio-respiratory autonomic function seems to translate into a
      lower rate of long term mortality. Ultra-short heart rate variability is a simple
      cardio-pulmonary fitness test which just requires 15 minutes, and involves no
      exercise such as in the treadmill or cycle test.

PMID- 22135481
TI  - Prevalence of hypertension in school going children of Surat city, Western India.
AB  - BACKGROUND: Early diagnosis of hypertension (HT) is an important strategy in its
      control. Previous studies have documented that hypertension may begin in
      adolescence, perhaps even in childhood. The purpose of this study was to
      determine the prevalence of hypertension and risk factors among school going
      children in Surat city, south Gujarat, India. MATERIALS AND METHODS: School going
      children aged between 6 to 18 years, of two schools were selected by purposive
      sampling method and blood pressure measurements were taken by mercury
      sphygmomanometer as per recommendation of American heart association.
      Hypertension is considered when blood pressure is more than 95(th) percentile
      according to update on task force report (2004) and children having hypertension
      in first and second recording repeat measurement was done to confirm hypertension
      after a week. RESULTS: Total prevalence of hypertension in our study was 6.48%.
      Hypertension in males was 6.74% (<10 yrs 5.88%, 10-13yrs 6.04%, >13yrs 9.19%) and
      in females was 6.13% (<10yrs 0.62%, 10-13yrs 8.67%,.13yrs 8.48%). Prevalence of
      obesity in hypertension was 8.7% against normotensive 1.1% (P <0.05). Prevalence
      of hypertension in family members of hypertensive was 18.6% and in normotensive
      13.1% (P =0.1). Prevalence of diabetes mellitus in family members of hypertensive
      was 23.4% and 13.7% in normotensive (P<0.05); while prevalence of ischemic heart
      disease in family members was 12.34% in hypertensive and 8.3% in normotensive (P
      <0.05). CONCLUSION: Prevalence of hypertension was 6.48% in the study subjects.
      We identified obesity, family history of diabetes mellitus, ischemic heart
      disease was found to be significant association for childhood hypertension.

PMID- 22135483
TI  - Truncus arteriosus: A major cause of proteinuria in children.
AB  - BACKGROUND: There are many studies about the association of nephropathy with
      congenital heart diseases (CHD), and the risk factors such as cyanosis and
      pulmonary hypertension have been evaluated. In our study, we have considered the
      relation of CHD associated nephropathy with other newer factors and the type of
      the structural heart defect. MATERIALS AND METHODS: A prospective cross sectional
      study was carried out. 48 children were selected on the basis of specific
      inclusion criteria, and reviewed over a period of 9 months. Nine different simple
      and complex structural heart defects were evaluated and compared after obtaining
      the imaging, blood and urine test results. RESULTS: Significant proteinuria
      occurred in 8 patients included in the study. More severe forms of pulmonary
      hypertension were observed in patients suffering from truncus arteriosus (TA);
      while the least values were detected in cases of pulmonary stenosis (PS) and
      tetralogy of fallot (TOF). The highest values of protein excretion were seen in
      patients of TA; and, the lowest values were observed in patients of PS and aortic
      stenosis (AS). Renal insufficiency was uncommon in infants and children with CHD.
      CONCLUSION: TA is an important cause of proteinuria among the infants and
      children suffering from CHD, probably because of the associated severe pulmonary
      hypertension (PH) and cyanosis. Also, proteinuria occurred at an earlier age in
      patients of TA as compared to other conditions, and was also found to be more
      severe if the TA was associated with moderate to severe tricuspid regurgitation.

PMID- 22135484
TI  - Accelerated atherosclerosis in a human immunodeficiency virus infected patient
      not on highly active anti-retroviral therapy: An autopsy case report.
AB  - The pandemic spread of human immunodeficiency virus (HIV) has been the greatest
      challenge to public health in modern times. However today, people infected with
      HIV are living longer due to highly active antiretroviral therapy (HAART). This
      has resulted in age related complications like cardiovascular diseases, causing
      increased morbidity and mortality. The relative contributions of HIV infection
      versus potential adverse effects of HAART to coronary heart disease risk remains
      unclear. Recent reports implicate both HIV infection per se and HAART therapy to
      cause metabolic derangements which are pro-atherogenic. Here, we report a case of
      HIV infected young patient never exposed to HAART, presenting with accelerated
      atherosclerosis in aorta, coronary and carotid arteries.

PMID- 22135485
TI  - Acute ST-segment elevation myocardial infarction from a centipede bite.
AB  - Acute myocardial infarction (AMI) following a centipede bite has been very rarely
      reported. Here, we describe a 22 year-old man who had ST-segment elevation AMI
      after a centipede bite. He presented with typical chest pain, electro and
      echocardiographic abnormalities, and elevated cardiac enzymes with normal
      coronary angiography. The probable mechanisms were described. Practitioners
      treating centipede bites shall not consider it lightly, as centipede envenomation
      may produce a variety of systemic and local manifestations in susceptible
      individuals.

PMID- 22135486
TI  - A case of cyanotic L-transposition with complete heart block in an adult female
      who had three in-hospital normal deliveries.
AB  - A 48-year-old female presented with complete heart block. On evaluation, it was
      diagnosed as a congenital cyanotic heart disease, namely, L-transposition of
      great arteries (L-TGA) with Fallot's physiology. She led the normal life of a
      manual laborer and had three hospital deliveries and yet escaped detection of her
      cardiac condition.

PMID- 22135487
TI  - The Polya Tree Sampler: Towards Efficient and Automatic Independent Metropolis
      Hastings Proposals.
AB  - We present a simple, efficient, and computationally cheap sampling method for
      exploring an un-normalized multivariate density on R(d), such as a posterior
      density, called the Polya tree sampler. The algorithm constructs an independent
      proposal based on an approximation of the target density. The approximation is
      built from a set of (initial) support points - data that act as parameters for
      the approximation - and the predictive density of a finite multivariate Polya
      tree. In an initial "warming-up" phase, the support points are iteratively
      relocated to regions of higher support under the target distribution to minimize
      the distance between the target distribution and the Polya tree predictive
      distribution. In the "sampling" phase, samples from the final approximating
      mixture of finite Polya trees are used as candidates which are accepted with a
      standard Metropolis-Hastings acceptance probability. Several illustrations are
      presented, including comparisons of the proposed approach to Metropolis-within
      Gibbs and delayed rejection adaptive Metropolis algorithm.

PMID- 22135488
TI  - Use of cluster analysis to describe desaturator phenotypes in COPD: correlations
      between pulmonary function tests and nocturnal oxygen desaturation.
AB  - BACKGROUND: Significant heterogeneity of clinical presentation and disease
      progression exists within chronic obstructive pulmonary disease (COPD). Although
      forced expiratory volume in 1 second (FEV(1)) inadequately describes this
      heterogeneity, a clear alternative has not emerged. This article discusses and
      refines the concept of phenotyping desaturators in COPD and shows a possible
      pattern which could be used as a framework for future research. RECENT FINDINGS:
      COPD is a complex condition with pulmonary and extrapulmonary manifestations. We
      suggest that COPD phenotypes should be associated with clinically meaningful
      outcomes. The innovation of COPD phenotyping is defined as COPD desaturators.
      Sleep-related hypoxemia and hypercapnia are well recognized in COPD and the
      development of systemic inflammation during sleep. These sleep-related changes
      predispose to nocturnal cardiac arrhythmias, pulmonary hypertension, and possibly
      death, particularly during acute exacerbations. CONCLUSION: A more focused
      definition makes possible a classification of patients into two distinct
      subgroups for both clinical and research purposes. Establishing a common language
      for future research will facilitate our understanding and management of such
      diseases. Even if different treatment strategies have different outcomes for
      these groups, we will have confirmation, or otherwise, of the clinical value of
      cluster analysis. This knowledge could lead to pharmacological treatment and
      other interventions directed to specific phenotypic groups.

PMID- 22135490
TI  - Severity of COPD at initial spirometry-confirmed diagnosis: data from medical
      charts and administrative claims.
AB  - PURPOSE: This study was conducted to determine COPD severity at the time of
      diagnosis as confirmed by spirometry in patients treated in a US managed care
      setting. PATIENTS AND METHODS: All patients with one or more inpatient stays, one
      or more emergency department visits, or two or more outpatient visits with
      diagnosis codes for COPD during 1994-2006 were identified from the Lovelace
      Patient Database. From this group, a subset of continuously enrolled patients
      with evidence in claims of a first available pulmonary function test or pulmonary
      clinic visit and a confirmatory claim for a COPD diagnosis was selected. Medical
      chart abstraction was undertaken for this subset to gather information for
      diagnosis and severity staging of each patient based on the Global Initiative for
      Chronic Obstructive Lung Disease (GOLD) criteria for COPD. RESULTS: Of the 12,491
      patients with a primary or secondary COPD diagnosis between 1994 and 2006, there
      were 1520 continuously enrolled patients who comprised the study cohort. Among
      the 648 eligible records from patients with evidence of a pulmonary function
      test, 366 were identified by spirometry as having COPD of GOLD stage I or higher
      (average percentage of predicted forced expiratory volume in 1 second: 60%): 19%
      were diagnosed at the stage of mild disease (GOLD stage I); 50% at moderate
      disease (GOLD stage II); and 31% at severe or very severe disease (GOLD stage III
      or IV, respectively). The majority of patients in these groups were not receiving
      maintenance treatment. CONCLUSION: The results demonstrate a very low incidence
      of early-stage diagnosis, confirmed by a pulmonary function test, of COPD in a
      large US sample and support calls for increased screening for COPD and treatment
      upon diagnosis.

PMID- 22135489
TI  - Safety-net facilities and hospitalization rates of chronic obstructive pulmonary
      disease: a cross-sectional analysis of the 2007 Texas Health Care Information
      Council inpatient data.
AB  - PURPOSE: Geographic disparities in hospitalization rates for chronic obstructive
      pulmonary disease (COPD) have been observed in Texas. However, little is known
      about the sources of these variations. The purpose of this manuscript is to
      further explore the geographic disparity of COPD hospitalization rates in Texas
      by examining county-level factors affecting access to care. PATIENTS AND METHODS:
      The study is a cross-sectional analysis of the 2007 Texas Health Care Information
      Council, Texas, demographer population projections and the 2009 Area Resource
      File (ARF). The unit of analysis was county-specific hospitalization rate,
      calculated as the number of discharges of county residents divided by county
      level population estimates. Indicators of access to care included: type of safety
      net facility and number of pulmonary specialists in a county. Safety-net
      facilities of interest were federally qualified health centers (FQHCs) and rural
      health clinics (RHCs). RESULTS: There was a significant difference (P < 0.05) in
      hospitalization rates according to health center presence. Counties with only
      FQHCs had the lowest COPD hospitalization rate (132 per 100,000 observations),
      and counties with only RHCs had the highest hospitalization rate (229 per 100,000
      observations). The presence of a pulmonary specialist was associated with a
      significant decrease (25%) in hospitalization rates among counties with only
      FQHCs. CONCLUSION: In Texas, counties with only FQHCs were associated with lower
      COPD hospitalization rates. The presence of a RHC alone may be insufficient to
      decrease hospitalizations from COPD. There are a number of factors that may
      contribute to these variations in hospitalization rates, such as racial/ethnic
      distribution, types and quality of services provided, and the level of rurality,
      which creates greater distances to care and lower concentration of hospitals and
      pulmonary specialists.

PMID- 22135491
TI  - Dyadic coping, quality of life, and psychological distress among chronic
      obstructive pulmonary disease patients and their partners.
AB  - BACKGROUND: Successfully coping with a chronic disease depends significantly on
      social support, particularly that of a significant other. Thus, it depends on the
      ways of dealing with stress within a couple (dyadic coping). In this study, the
      relationship between dyadic coping and well-being was investigated among couples
      in which one partner suffers from chronic obstructive pulmonary disease (COPD).
      METHODS: A total of 43 couples participated. They were mailed questionnaires on
      anxiety and depression (Hospital Anxiety and Depression Scale), quality of life
      (World Health Organization Quality of Life Questionnaire-BREF), and dyadic coping
      (Dyadic Coping Inventory). RESULTS: Low scores of positive and high scores of
      negative dyadic coping were associated with poorer quality of life and higher
      psychological distress among couples. Delegated coping (assistance with daily
      tasks) was higher among partners. When estimated by patients, high delegated
      partner coping (frequent provision of support by partners) and low delegated
      personal coping (low provision of support by patients) were associated with
      poorer quality of life for both patient and partner. COPD patients suffering from
      depression were supported more often and attributed deficits in dyadic coping
      primarily to themselves, whereas partners with higher scores of depression
      provided higher estimates of both their own negative coping and the negative
      coping of their partner. CONCLUSION: The higher the patient perceived the
      imbalance in delegated dyadic coping, the lower the couple's quality of life.
      More negative and less positive dyadic coping were associated with lower quality
      of life and higher psychological distress. Psychotherapeutic interventions to
      improve dyadic coping may lead to better quality of life and less psychological
      distress among COPD patients and their partners.

PMID- 22135492
TI  - Asthma, chronic obstructive pulmonary disease, or both? Diagnostic labeling and
      spirometry in primary care patients aged 40 years or more.
AB  - AIMS: To describe symptoms and lung function in patients registered with asthma
      or chronic obstructive pulmonary disease (COPD) in primary care and to examine
      how spirometry findings fit with general practitioners' (GPs) diagnoses. METHODS:
      Patients aged >=40 years with a diagnosis of asthma or COPD registered in the
      electronic medical record during the previous 5 years were recruited at seven GP
      offices in Norway in 2009-2010. Registered diagnosis, spirometry results,
      comorbidity, and reported symptoms were compared. RESULTS: Among 376 patients,
      62% were women. Based on Global Initiative for Chronic Obstructive Lung Diseases
      criteria, a spirometry diagnosis of COPD could be made in 68.1% of the patients
      with a previous COPD diagnosis and in 17.1% of those diagnosed with asthma only
      (P < 0.001). The kappa agreement between last clinical diagnosis of COPD and COPD
      based on spirometry was 0.50. A restrictive spirometry pattern was found in 19.4%
      and more frequently in patients diagnosed with both asthma and COPD (23.9%) than
      in patients diagnosed with COPD only (6.8%, P = 0.003). CONCLUSION: The ability
      of GPs to differentiate between asthma and COPD seems to have considerably
      improved during the last decade, probably due to the dissemination of spirometry
      and guidelines for COPD diagnosis. A diagnosis of COPD that cannot be confirmed
      by spirometry represents a challenge in clinical practice, in particular when a
      restrictive pattern on spirometry is found.

PMID- 22135494
TI  - Medication prescribing errors in the intensive care unit of Jimma University
      Specialized Hospital, Southwest Ethiopia.
AB  - BACKGROUND: A number of studies indicated that prescribing errors in the
      intensive care unit (ICU) are frequent and lead to patient morbidity and
      mortality, increased length of stay, and substantial extra costs. In Ethiopia,
      the prevalence of medication prescribing errors in the ICU has not previously
      been studied. OBJECTIVE: To assess medication prescribing errors in the ICU of
      Jimma University Specialized Hospital (JUSH), Southwest Ethiopia. METHODS: A
      cross-sectional study was conducted in the ICU of Jimma University Specialized
      Hospital from February 7 to April 15, 2011. All medication-prescribing
      interventions by physicians during the study period were included in the study.
      Data regarding prescribing interventions were collected from patient cards and
      medication charts. Prescribing errors were determined by comparing prescribed
      drugs with standard treatment guidelines, textbooks, handbooks, and software.
      Descriptive statistics were generated to meet the study objective. RESULTS: The
      prevalence of medication prescribing errors in the ICU of Jimma University
      Specialized Hospital was 209/398 (52.5%). Common prescribing errors were using
      the wrong combinations of drugs (25.7%), wrong frequency (15.5%), and wrong dose
      (15.1%). Errors associated with antibiotics represented a major part of the
      medication prescribing errors (32.5%). CONCLUSION: Medication errors at the
      prescribing phase were highly prevalent in the ICU of Jimma University
      Specialized Hospital. Health care providers need to establish a system which can
      support the prescribing physicians to ensure appropriate medication prescribing
      practices.

PMID- 22135493
TI  - The effects of long-term noninvasive ventilation in hypercapnic COPD patients: a
      randomized controlled pilot study.
AB  - INTRODUCTION: Noninvasive ventilation (NIV) is a well-established treatment for
      acute-on- chronic respiratory failure in hypercapnic COPD patients. Less is known
      about the effects of a long-term treatment with NIV in hypercapnic COPD patients
      and about the factors that may predict response in terms of improved oxygenation
      and lowered CO(2) retention. METHODS: In this study, we randomized 15 patients to
      a routine pharmacological treatment (n = 5, age 66 [standard deviation +/- 6]
      years, FEV(1) 30.5 [+/-5.1] %pred, PaO(2) 65 [+/-6] mmHg, PaCO(2) 52.4 [+/-6.0]
      mmHg) or to a routine treatment and NIV (using the Synchrony BiPAP device
      [Respironics, Inc, Murrsville, PA]) (n = 10, age 65 [+/-7] years, FEV(1) 29.5 [+/
      9.0] %pred, PaO(2) 59 [+/-13] mmHg, PaCO(2) 55.4 [+/-7.7] mmHg) for 6 months. We
      looked at arterial blood gasses, lung function parameters and performed a low
      dose computed tomography of the thorax, which was later used for segmentation
      (providing lobe and airway volumes, iVlobe and iVaw) and post-processing with
      computer methods (providing airway resistance, iRaw) giving overall a functional
      image of the separate airways and lobes. RESULTS: In both groups there was a
      nonsignificant change in FEV(1) (NIV group 29.5 [9.0] to 38.5 [14.6] %pred,
      control group 30.5 [5.1] to 36.8 [8.7] mmHg). PaCO(2) dropped significantly only
      in the NIV group (NIV: 55.4 [7.7] -> 44.5 [4.70], P = 0.0076; control: 52.4 [6.0]
      -> 47.6 [8.2], NS). Patients actively treated with NIV developed a more
      inhomogeneous redistribution of mass flow than control patients. Subsequent
      analysis indicated that in NIV-treated patients that improve their blood gases,
      mass flow was also redistributed towards areas with higher vessel density and
      less emphysema, indicating that flow was redistributed towards areas with better
      perfusion. There was a highly significant correlation between the % increase in
      mass flow towards lobes with a blood vessel density of >9% and the increase in
      PaO(2). Improved ventilation-perfusion match and recruitment of previously
      occluded small airways can explain the improvement in blood gases. CONCLUSION: We
      can conclude that in hypercapnic COPD patients treated with long-term NIV over 6
      months, a mass flow redistribution occurs, providing a better ventilation
      perfusion match and hence better blood gases and lung function. Control patients
      improve homogeneously in iVaw and iRaw, without improvement in gas exchange since
      there is no improved ventilation/perfusion ratio or increased alveolar
      ventilation. These differences in response can be detected through functional
      imaging, which gives a more detailed report on regional lung volumes and
      resistances than classical lung function tests do. Possibly only patients with
      localized small airway disease are good candidates for long-term NIV treatment.
      To confirm this and to see if better arterial blood gases also lead to better
      health related quality of life and longer survival, we have to study a larger
      population.

PMID- 22135495
TI  - A systematic review of randomized controlled trials on exercise parameters in the
      treatment of patellofemoral pain: what works?
AB  - PURPOSE: There is research evidence which supports the effectiveness of exercise
      in reducing pain and increasing function in patients with patellofemoral pain
      syndrome. However, what is unclear are the parameters underpinning this
      intervention. This has led to uncertainty when operationalizing exercises for
      patients with patellofemoral pain syndrome in clinical practice. The aim of this
      review was to evaluate the parameters of exercise programs reported in primary
      research, to provide clinicians with evidence-based recommendations for exercise
      prescription for patellofemoral pain. METHODS: A systematic review of randomized
      controlled trials was undertaken. Only trials that identified exercise to be
      effective in treating patellofemoral pain were included. Appropriate databases
      and reference lists were searched using established keywords. Data relating to
      common exercise parameters such as the type of exercise, length, and frequency of
      intervention, intensity, repetitions, sets, and specific technique were
      extracted, along with details of co-interventions that may have been used.
      RESULTS: A total of ten randomized controlled trials were included in this review
      and from these trials 14 interventions arms were evaluated. All 14 interventions
      focused on active exercises, all but two of which also included a passive
      stretching component. The current body of evidence demonstrates positive results
      with exercise interventions such as knee extension, squats, stationary cycling,
      static quadriceps, active straight leg raise, leg press, and step-up and down
      exercises for patients with patellofemoral pain syndrome. A progressive regime of
      daily exercises of two to four sets of ten or more repetitions over an
      intervention period of 6 weeks or more, combined with exercises to address
      flexibility of the lower limb musculature was commonly used. CONCLUSION:
      Currently, the primary research on this topic supports the use of closed kinetic
      chain, strengthening exercises for musculature of the lower limb, combined with
      flexibility options. The current evidence base supports a prescription of daily
      exercises of two-four sets of ten or more repetitions over a period of 6 weeks or
      more.

PMID- 22135496
TI  - Integrating evidence into practice: use of McKenzie-based treatment for
      mechanical low back pain.
AB  - Low back pain (LBP) is a major health issue with significant socioeconomic
      implications in most Western countries. Many forms of treatment have been
      proposed and investigated in the past, with exercise being a commonly prescribed
      intervention. Within allied health, in particular physiotherapy, there has been a
      growing movement that recognizes the role of the McKenzie method in treating LBP.
      Within the McKenzie framework, directional preference (DP) exercises are one such
      intervention, with preliminary data demonstrating its effectiveness in the
      management of LBP. In this paper, we aim to integrate the evidence from current
      research, identified using a systematic review, and utilize a practical real-life
      case scenario to outline how evidence from the literature can be implemented in
      clinical practice. The findings from the systematic review indicate that DP
      exercises may have positive effects in the management of LBP. While the body of
      evidence to support this is limited (only four studies) and therefore modest at
      best, it does provide some emerging evidence to support the use of DP exercises
      in clinical practice. Despite this, gaps also persist in the literature on DP
      exercises, and this relates to the exercise parameters and the compliance rates.
      Recognizing this dichotomy (modest evidence in some areas and evidence gaps in
      other areas), which is likely to confront health practitioners, using a practical
      approach with a real-life clinical scenario, we outline how the evidence from the
      systematic review can be implemented in clinical practice. This approach builds
      on the philosophy of evidence-based practice of integrating research evidence
      with clinical expertise and patient values.

PMID- 22135497
TI  - Role of rheumatology clinical nurse specialists in optimizing management of hand
      osteoarthritis during daily practice in secondary care: an observational study.
AB  - BACKGROUND: The purpose of this study was to describe the effectiveness of a
      single one-hour consultation by a clinical nurse specialist in patients with hand
      osteoarthritis during daily rheumatology practice in secondary care. METHODS:
      Consecutive patients diagnosed by rheumatologists to have primary hand
      osteoarthritis and referred to the clinical nurse specialist were eligible for
      entry into this study. The standardized 1-hour consultation consisted of
      assessments and education on hand osteoarthritis by a clinical nurse specialist.
      Before and 3 months after the consultation, assessments were done to evaluate
      treatment (use of assistive devices, acetaminophen), health-related quality of
      life (physical component summary [PCS] score of Short-Form 36), and hand
      pain/function (Australian/ Canadian Osteoarthritis Hand Index [AUSCAN]). Paired t
      tests and McNemar tests were used to analyze differences between baseline and
      follow-up. Satisfaction was measured after consultation at follow-up using a
      multidimensional questionnaire comprising 13 items (rated on a four-point scale).
      RESULTS: A total of 439 patients were referred, with follow-up data available for
      195 patients, comprising 177 (87%) females, and of mean age 59 +/- 9.0 years.
      After consultation, the proportions of patients using assistive devices and/or
      acetaminophen increased significantly from 30% to 39% and from 35% to 49%,
      respectively. PCS improved significantly (P = 0.03) whereas AUSCAN hand
      pain/function showed no significant differences compared with baseline (P values
      0.52 and 0.92, respectively). The proportions of patients reporting to be
      satisfied or fully satisfied ranged from 78% to 99% per item. CONCLUSION: A
      single, comprehensive, standardized assessment and education by a clinical nurse
      specialist improved the physical dimension of health-related quality of life in
      hand osteoarthritis. Most patients were satisfied with the consultation. Further
      controlled trials are needed to determine the added value of the clinical nurse
      specialist in care for hand osteoarthritis.

PMID- 22135498
TI  - What patients want and need to know about atrial fibrillation.
AB  - Clinicians in a variety of settings are called upon to care for patients
      diagnosed with atrial fibrillation (AF), a common chronic condition that affects
      up to 3 million people in the USA. Evidence-based guidelines provide clinicians
      with direction for treatment of AF, but recommended content for educating
      patients and counseling about self-management of AF is not included in published
      guidelines. When patients believe they have a good understanding of AF they
      report fewer symptoms, perceive greater control over AF, and attribute less
      emotional distress to AF. Thus, providing patients with information about AF and
      how to manage it is important for promoting positive outcomes. The purpose of
      this article is to offer evidence-based recommendations for content to include in
      self-management education and counseling for patients with AF. Approaches for
      educating and counseling patients related to AF pathophysiology, the nature of AF
      (its cause, consequences, and trajectory), treatments, action plans, and symptom
      management, and managing the psychosocial challenges of living with AF, are
      discussed.

PMID- 22135500
TI  - Clinical and behavioral factors associated with management outcome in
      hospitalized patients with diabetic foot ulcer.
AB  - OBJECTIVES: Diabetic foot ulcer (DFU) has been linked to high mortality and
      morbidity in diabetic patients. In spite of the increasing prevalence of diabetes
      and its complications, this issue has not been adequately studied in Iran.
      MATERIALS AND METHODS: In this cross-sectional study we attempt to describe the
      prevalence of diabetic foot amputation in patients admitted to our training
      hospitals in Urmia, Iran, and also to determine the associated demographic,
      behavioral, and clinical factors. RESULTS: Of 94 patients with DFU, 34 (32%) had
      amputation. Those with amputation were significantly older and were also less
      educated than those without amputation, had longer duration of diabetes (hence
      were more likely to suffer from complications), and had high-risk wounds plus a
      poor glycemic control. On logistic regression analysis two variables were
      associated with amputation: Wagner classification >=3 and HbA(1c). On a receiver
      operating characteristics curve, the HbA(1c) cutoff point of 9.7% significantly
      discriminated to predict increasing risk of amputation. CONCLUSION: Both glycemic
      control and promoting the knowledge of patients and health care professionals in
      order to diagnose DFU in the early stages and to prevent development of the high
      grade wounds would be a significant step in reducing the burden of DFU and its
      effect on quality of life in Iran.

PMID- 22135499
TI  - Management of diabetes across the course of disease: minimizing obesity
      associated complications.
AB  - Obesity increases the risk for developing type 2 diabetes mellitus (T2DM) and
      this in turn correlates with an elevated probability of long-term diabetes
      complications once diabetes is established. Interventions aimed at lowering
      weight via changes in diet and lifestyle have repeatedly been shown to improve
      glycemic control in patients with T2DM and even to reverse early disease. Weight
      gain, a potential side effect of treatment for patients with T2DM, is also an
      important concern, and it has been noted that weight increases associated with
      antidiabetes therapy may blunt cardiovascular risk reductions achieved by
      decreasing blood glucose. Among older agents, metformin and acarbose have the
      lowest risk for weight gain, while sulfonylureas, meglitinides, and
      thiazolidinediones are all associated with weight increases. Clinical trial
      results have also consistently demonstrated that treatment with glucagon-like
      peptide-1 receptor agonists and amylin lowers weight, and that dipeptidyl
      peptidase-4 inhibitors are weight neutral in patients with T2DM. Conventional
      human insulin formulations are known to increase weight in patients with T2DM.
      However, some insulin analogs, particularly insulin detemir, have lower liability
      for this adverse event. The use of both pharmacologic and surgical therapies
      aimed at treating obesity rather than lowering blood glucose have the potential
      to improve glycemic control and even resolve T2DM in some patients.

PMID- 22135501
TI  - Use of electronic medical records (EMR) for oncology outcomes research: assessing
      the comparability of EMR information to patient registry and health claims data.
AB  - Electronic medical records (EMRs) are used increasingly for research in clinical
      oncology, epidemiology, and comparative effectiveness research (CER). OBJECTIVE:
      To assess the utility of using EMR data in population-based cancer research by
      comparing a database of EMRs from community oncology clinics against Surveillance
      Epidemiology and End Results (SEER) cancer registry data and two claims databases
      (Medicare and commercial claims). STUDY DESIGN AND SETTING: DEMOGRAPHIC,
      CLINICAL, AND TREATMENT PATTERNS IN THE EMR, SEER, MEDICARE, AND COMMERCIAL
      CLAIMS DATA WERE COMPARED USING SIX TUMOR SITES: breast, lung/bronchus,
      head/neck, colorectal, prostate, and non-Hodgkin's lymphoma (NHL). We identified
      various challenges in data standardization and selection of appropriate
      statistical procedures. We describe the patient and clinic inclusion criteria,
      treatment definitions, and consideration of the administrative and clinical
      purposes of the EMR, registry, and claims data to address these challenges.
      RESULTS: Sex and 10-year age distributions of patient populations for each tumor
      site were generally similar across the data sets. We observed several differences
      in racial composition and treatment patterns, and modest differences in
      distribution of tumor site. CONCLUSION: Our experience with an oncology EMR
      database identified several factors that must be considered when using EMRs for
      research purposes or generalizing results to the US cancer population. These
      factors were related primarily to evaluation of treatment patterns, including
      evaluation of stage, geographic location, race, and specialization of the medical
      facilities. While many specialty EMRs may not provide the breadth of data on
      medical care, as found in comprehensive claims databases and EMR systems, they
      can provide detailed clinical data not found in claims that are extremely
      important in conducting epidemiologic and outcomes research.

PMID- 22135502
TI  - Characteristics of Dutch and Swiss primary care COPD patients - baseline data of
      the ICE COLD ERIC study.
AB  - INTRODUCTION: INTERNATIONAL COLLABORATIVE EFFORT ON CHRONIC OBSTRUCTIVE LUNG
      DISEASE: Exacerbation Risk Index Cohorts (ICE COLD ERIC) is a prospective cohort
      study with chronic obstructive pulmonary disease (COPD) patients from Switzerland
      and The Netherlands designed to develop and validate practical COPD risk indices
      that predict the clinical course of COPD patients in primary care. This paper
      describes the characteristics of the cohorts at baseline. MATERIAL AND METHODS:
      Standardized assessments included lung function, patient history, self
      administered questionnaires, exercise capacity, and a venous blood sample for
      analysis of biomarkers and genetics. RESULTS: A total of 260 Dutch and 151 Swiss
      patients were included. Median age was 66 years, 57% were male, 38% were current
      smokers, 55% were former smokers, and 76% had at least one and 40% had two or
      more comorbidities with cardiovascular disease being the most prevalent one. The
      use of any pulmonary and cardiovascular drugs was 84% and 66%, respectively.
      Although lung function results (median forced expiratory volume in 1 second
      [FEV(1)] was 59% of predicted) were similar across the two cohorts, Swiss
      patients reported better COPD-specific health-related quality of life (Chronic
      Respiratory Questionnaire) and had higher exercise capacity. DISCUSSION: COPD
      patients in the ICE COLD ERIC study represent a wide range of disease severities
      and the prevalence of multimorbidity is high. The rich variation in these primary
      care cohorts offers good opportunities to learn more about the clinical course of
      COPD.

PMID- 22135503
TI  - Hip fracture history and risk of nonmelanoma skin cancer: a Danish population
      based study.
AB  - BACKGROUND: Vitamin D deficiency is associated with osteoporotic fractures, such
      as hip fracture. Sun exposure, the natural source of vitamin D, is the main risk
      factor for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In this
      study, we examined the association between a history of hip fracture and risk of
      BCC and SCC. METHODS: We conducted a population-based case-controlled study using
      data on BCC and SCC cases registered in the Danish Cancer Registry from 1990
      2005. For each case, we selected five population controls matched by age and
      gender. We used conditional logistic regression to compute odds ratios (OR) and
      95% confidence intervals (CI), while adjusting for chronic diseases and
      socioeconomic status. RESULTS: A history of hip fracture was associated with a
      decreased risk of BCC (OR 0.90, 95% CI 0.85-0.94), which was most pronounced in
      cases of tumors on the trunk, extremities, or at multiple sites. We found no
      association for SCC (OR 1.07, 95% CI 0.98-1.17). CONCLUSION: Our study showed an
      inverse association between history of hip fracture and risk of BCC, but not of
      SCC. Sun exposure, resulting in vitamin D synthesis, may explain the link between
      the two diseases.

PMID- 22135506
TI  - It's Time for Doctors to Speak Out on Climate Change.

PMID- 22135505
TI  - Potential for modulation of the fas apoptotic pathway by epidermal growth factor
      in sarcomas.
AB  - One important mechanism by which cancer cells parasitize their host is by
      escaping apoptosis. Thus, selectively facilitating apoptosis is a therapeutic
      mechanism by which oncotherapy may prove highly advantageous. One major apoptotic
      pathway is mediated by Fas ligand (FasL). The death-inducing signaling Ccmplex
      (DISC) and subsequent death-domain aggregations are created when FasL is bound by
      its receptor thereby enabling programmed cell death. Conceptually, if a better
      understanding of the Fas pathway can be garnered, an oncoselective prodeath
      therapeutic approach can be tailored. Herein, we propose that EGF and CTGF play
      essential roles in the regulation of the Fas apoptotic pathway in sarcomas. Tumor
      and in vitro data suggest viable cells counter the prodeath signal induced by
      FasL by activating EGF, which in turn induces prosurvival CTGF. The prosurvival
      attributes of CTGF ultimately predominate over the death-inducing FasL. Cells
      destined for elimination inhibit this prosurvival response via a presently
      undefined pathway. This scenario represents a novel role for EGF and CTGF as
      regulators of the Fas pathway in sarcomas.

PMID- 22135504
TI  - Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma.
AB  - Ewing's sarcoma family tumors (ESFT) are characterized by specific chromosomal
      translocations, which give rise to EWS-ETS chimeric proteins. These aberrant
      transcription factors are the main pathogenic drivers of ESFT. Elucidation of the
      factors influencing EWS-ETS expression and/or activity will guide the development
      of novel therapeutic agents against this fatal disease.

PMID- 22135508
TI  - A study of learning environments in the kulliyyah (faculty) of nursing,
      international islamic university malaysia.
AB  - BACKGROUND: In a nursing programme, the main objective is to produce nursing
      graduates who can provide comprehensive care and treatment to the community. A
      good approach to the systematic design of a learning environment can lead to
      positive outcomes for graduates. The learning environment is more than student
      teacher interaction, teaching and learning activities. Good physical structures
      and facilities provided by the university are important, too. Furthermore, the
      university must also be concerned about meeting students' psychosocial and
      emotional needs. The aim of this study is to measure the learning environment by
      administering the Dundee Ready Educational Environment Measure (DREEM)
      questionnaire to students across the four years of the Bachelor of Nursing
      programme at the Faculty of Nursing, IIUM, and to identify areas for change that
      may contribute to a more meaningful student learning experience. METHODS: The
      DREEM questionnaire was administered to 105 Bachelor of Nursing students at IIUM.
      RESULTS: The total mean score on the 50-item DREEM inventory was 120.12 out of a
      maximum of 200. Student perceptions of learning and their teachers, their
      academic self, social self and their perception of the atmosphere were all
      positive. Eight items with low mean scores (less than two) on the DREEM
      questionnaire were identified as requiring remediation. CONCLUSION: The
      implications include the need to create and maintain a supportive environment, in
      addition to designing and implementing interventions to remedy unsatisfactory
      elements of the learning environment if effective and successful teaching and
      learning are to be realised. Thus, specific remedial steps to improve the student
      learning environment of the Faculty of Nursing, IIUM are described.

PMID- 22135507
TI  - Identification of Dengue-specific B-Cell Epitopes by Phage-display Random Peptide
      Library.
AB  - BACKGROUND: Dengue is the most important human viral disease transmitted by
      arthropod vectors. The availability of random peptide libraries (RPL) displayed
      on phage has provided a powerful tool for selecting sequences that mimic epitopes
      from microorganisms that are useful for diagnostic and vaccine development
      purposes. In this paper, we describe peptides that resemble the antigenic
      structure of B-cell epitopes of dengue virus identified from a phage-peptide
      library using human sera containing polyclonal antibodies against dengue virus.
      MATERIALS AND METHODS: Eighteen phage clones were isolated from the phage-display
      peptide library, J404, by affinity selection using human antisera against dengue
      virus type 3. These clones were tested for reactivity by ELISA with a panel of
      hyperimmune ascitic fluids (HAFs) containing antibodies either against all four
      dengue serotypes, West Nile virus (WNV) or Eastern equine encephalitis virus
      (EEEV) with control ascitic fluid (NAF) used as a negative control. RESULTS:
      Eight clones were recognized by HAFs against the four dengue serotypes, of which
      four significantly inhibited binding of anti-dengue antibodies to the virus. Two
      peptides with similar sequences to regions of NS3 and NS4B non-structural dengue
      virus proteins were identified. CONCLUSION: Our results suggest that these
      peptides could be used for the development of diagnostic tools for the detection
      of dengue virus infection and for a potential vaccine against this pathogen.

PMID- 22135509
TI  - Prognostic factors of severe traumatic brain injury outcome in children aged 2-16
      years at a major neurosurgical referral centre.
AB  - BACKGROUND: Traumatic Brain Injury (TBI) in children has been poorly studied, and
      the literature is limited. We evaluated 146 children with severe TBI (coma score
      less than 8) in an attempt to establish the prognostic factors of severe TBI in
      children. METHODS: The severity of TBI was assessed via modified Glasgow Coma
      Score for those more than 3 years old and via Children Coma Score for those under
      3 years old. Clinical presentations, laboratory parameters and features of
      Computerised Tomography brain scans were analyzed. Outcomes were assessed at 6
      months with the Pediatric Cerebral Performance Categories Scale; the outcomes
      were categorised as good or poor outcomes. Correlations with outcome were
      evaluated using univariate and multivariate logistic models. RESULTS: A low coma
      score upon admission was independently associated with poor outcome. The presence
      of diabetes insipidus within 3 days post-TBI (OR: 1.9), hyperglycaemia (OR: 1.2),
      prolonged PT ratio (OR: 2.3) and leukocytosis (OR: 1.1) were associated with
      poorer outcome. CONCLUSION: Knowledge of these prognostic factors helps
      neurosurgeons and neurocritical care specialists to manage and improve outcome in
      severe TBI in children.

PMID- 22135510
TI  - Superselective embolisation in acute lower gastrointestinal haemorrhage: a single
      institution experience.
AB  - BACKGROUND: Superselective embolisation has been recognised as integral in the
      management of lower gastrointestinal haemorrhage. It has also reduced the need
      for emergency surgery. The objective of this case series was to describe the
      lower gastrointestinal haemorrhage cases seen in our centre, its diagnosis and
      the role of superselective embolisation in patient management. METHODS: All
      patients who underwent superselective embolisation from January 2008 until April
      2009 in our centre were analysed. Data were collected from the hospital
      electronic medical records. RESULTS: Four patients (three males) with a mean age
      of 81 years were analysed. Multidetector computerised tomography and digital
      subtraction angiography were positive in all patients. Superselective
      embolisation with platinum microcoils was performed in all patients (n = 4).
      Technical success was achieved in all patients (100%). CONCLUSION: Superselective
      embolisation in the treatment of lower gastrointestinal haemorrhage is safe and
      effective with a very high technical success rate.

PMID- 22135511
TI  - Dreams In Jungian Psychology: The use of Dreams as an Instrument For Research,
      Diagnosis and Treatment of Social Phobia.
AB  - BACKGROUND: The significance of dreams has been explained in psychoanalysis,
      depth psychology and gestalt therapy. There are many guidelines in analytic
      psychology for dream interpretation and integration in clinical practice. The
      present study, based on the Jungian analytic model, incorporated dreams as an
      instrument for assessment of aetiology, the psychotherapy process and the outcome
      of treatment for social phobia within a clinical case study. METHOD: This case
      study describes the use of dream analysis in treating a female youth with social
      phobia. RESULTS: The present findings supported the three stage paradigm
      efficiency in the Jungian model for dream working within a clinical setting, i.e.
      written details, reassembly with amplification and assimilation. It was indicated
      that childhood and infantile traumatic events, psychosexual development
      malfunctions, and inefficient coping skills for solving current life events were
      expressed in the patient's dreams. CONCLUSION: Dreams can reflect a patient's
      aetiology, needs, illness prognosis and psychotherapy outcome. Dreams are an
      instrument for the diagnosis, research and treatment of mental disturbances in a
      clinical setting.

PMID- 22135512
TI  - Challenges in the management of nasopharyngeal carcinoma: a review.
AB  - Nasopharyngeal carcinoma (NPC) is a non-lymphomatous, squamous cell carcinoma
      that occurs in the epithelial lining of the nasopharynx, an area that shows
      varying degrees of differentiation. Although relatively rare worldwide, NPC has
      substantial incidence and mortality in populations in Southeast Asia and in
      people with Southern Chinese ancestry. In Malaysia, NPC is a leading cancer type.
      In the clinic, NPC presents on a very wide spectrum. Therefore, a high degree of
      suspicion on the part of the clinician and an increased awareness by the patient
      is essential for the recognition of an early lesion. Early detection of the
      cancer is important as it affects the patient's prognosis and the mode of
      treatment. Managing patients with NPC is very challenging as patients usually
      present late when the cancer is already in an advanced stage. Here, we review the
      challenges in the management of NPC.

PMID- 22135513
TI  - Retrospective review of outcomes of a multimodal chronic pain service in a major
      teaching hospital: a preliminary experience in universiti sains malaysia.
AB  - BACKGROUND: Chronic pain is a common medical issue. Beside chronic devastating
      pain, patients also suffer dysfunction more generally, including in the physical,
      emotional, social, recreational, vocational, financial, and legal spheres.
      Integrated multidisciplinary and multimodal chronic pain management programmes
      offer clear evidence for relief of suffering and return to functional lifestyles.
      MATERIALS AND METHODS: This retrospective review was performed in order to
      evaluate one-year outcomes among all newly referred patients of the multimodal
      chronic pain service at Hospital Universiti Sains Malaysia (HUSM). All patients
      received multimodal pain therapy, including pharmacological, physical, and
      psychological therapy, exercise, and pain intervention. The variables evaluated
      were based on a patient's global pain assessments, which were made using the
      Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI), modified by
      patient self-report, and were taken within days to months of commencing our
      multimodal pain regime. RESULTS: A total of 169 patients were enrolled in this
      study. Out of this number, 102 (60.4%) were seen at the pain clinic, and 67
      (39.6%) were referred while they were inpatients. About one-third of the patients
      had chronic pain due to cancer. Our data showed that 128 (75.7%) of our chronic
      pain patients were successfully managed when >=50% of pain relief (as measured by
      their VAS score) was achieved at any point during the course of the study period.
      In addition, 104 patients (61.5%) showed improvement in their modified ODI by 50%
      or more. CONCLUSION: A multimodal chronic pain service plays a significant role
      in managing chronic pain patients in a major hospital, as it is capable of
      delivering comprehensive and attainable care to manage refractory and intractable
      chronic pain.

PMID- 22135514
TI  - Alum irrigation for the treatment of intractable haematuria.
AB  - Managing intractable haematuria is a daunting task. One cause of this condition
      is radiationinduced haemorrhagic cystitis. Several treatments for the condition
      have been proposed and one non-invasive option is alum irrigation. Here, we
      report on a 65-year-old woman with intractable haematuria secondary to radiation
      cystitis who was successfully treated with alum irrigation. Alum irrigation is
      safe, well tolerated and relatively cheap. A review of the literature and a
      comprehensive discussion on alum irrigation as treatment for haematuria is
      discussed here to create an awareness regarding this treatment option.

PMID- 22135515
TI  - Calcification of the Alar Ligament Mimics Fracture of the Craniovertebral
      Junction (CVJ): An Incidental Finding from Computerised Tomography of the
      Cervical Spine Following Trauma.
AB  - When performing a radiological assessment for a trauma case with associated head
      injury, a fragment of dense tissue detected near the craniovertebral junction
      would rapidly be assessed as a fractured bone fragment. However, if further
      imaging and evaluation of the cervical spine with computerised tomography (CT)
      did not demonstrate an obvious fracture, then the possibility of ligament
      calcification would be considered. We present a case involving a previously
      healthy 44-yearold man who was admitted following a severe head injury from a
      road traffic accident. CT scans of the head showed multiple intracranial
      haemorrhages, while scans of the cervical spine revealed a small, well-defined,
      ovoid calcification in the right alar ligament. This was initially thought to be
      a fracture fragment. Although such calcification is uncommon, accident and
      emergency physicians and radiologists may find this useful as a differential
      diagnosis in patients presenting with neck pain or traumatic head injury.

PMID- 22135516
TI  - Acute Tonsillitis With Concurrent Kikuchi's Disease as a Cause of Persistent
      Lymphadenopathy.
AB  - We present a young adult female with symptoms of acute tonsillitis and tender
      cervical lymphadenopathy. Despite a full course of oral antibiotics, she had
      persistent left lower cervical lymphadenopathy measuring 2.0 x 1.5 cm at 2 weeks
      post-treatment. Rigid and flexible scope examinations did not reveal any
      abnormalities in the nasopharynx, oropharynx or hypopharynx. Tuberculosis tests
      were negative and blood index results were normal. Fine needle aspiration
      cytology revealed a non-specific granulomatous inflammatory process. Excisional
      lymph node biopsy was performed, and the patient was diagnosed as having
      Kikuchi's Disease (KD). We would like to highlight the diagnostic challenges in
      detecting this condition and the importance of differentiating KD from
      tuberculosis and malignant lymphoma, the latter of which requires aggressive
      treatment.

PMID- 22135517
TI  - Non-detection of Acute Angiography-induced Cerebral Vasospasm by Transcranial
      Doppler Sonography amongst Patients with Subarachnoid Haemorrhage in Kelantan.

PMID- 22135518
TI  - Healthcare as a bottomless pit.

PMID- 22135519
TI  - Role of Pioglitazone with Metformin or Glimepiride on Oxidative Stress-induced
      Nuclear Damage and Reproductive Toxicity in Diabetic Rats.
AB  - BACKGROUND: Oxidative stress due to improper control of blood glucose in chronic
      diabetes plays a major role in the development of secondary complications
      including cancer and birth defect. The aim of this study is to evaluate the
      protective effect of combination of pioglitazone with metformin or glimepiride
      against the experimental type-2 diabetes induced nuclear damage and reproductive
      toxicity in rats. METHODS: The combinations of Pioglitazone (Pio-1 mg/kg) with
      metformin (Met-50 mg/kg) or glimepiride (Gmp-0.2 mg/kg) given orally daily for 4
      weeks were tested against nicotinamide (NA-230 mg/kg, ip)-streptozotocin (STZ-65
      mg/kg, ip)-induced micronuclei (MN) formation and sperm abnormalities in male
      Wistar rats. The antioxidant status was evaluated by measuring the levels of
      serum lipid peroxidation (LPO), catalase (CAT) and superoxide dismutase (SOD).
      RESULTS: The administration of Pio+Met significantly (P<0.01) reduced the number
      of micronucleated erythrocytes, increased the polychromatic: normochromatic
      erythrocytes (P/N ratio), reduced (P<0.001) sperm morphology defects and
      increased (P<0.05) the caudal sperm count compared to the untreated diabetic
      condition. Furthermore, the Pio+Met combination enhanced the antioxidant status
      in diabetic animals. However, Pio+Gmp did not attenuate the nuclear and sperm
      defects or oxidative stress. CONCLUSIONS: The observations suggest that Pio+Met
      combination reduced nuclear damage and sperm abnormalities by enhancing the
      antioxidant status in the diabetic animals.

PMID- 22135520
TI  - HIV- and AIDS-related Ocular Manifestations in Tanzanian Patients.
AB  - BACKGROUND: Although around 70% of HIV+ cases used to have ocular manifestations,
      the late reporting of cases often results in severe forms of ocular morbidity
      that would otherwise have been prevented. The objective of this study was to
      describe the ocular manifestations of HIV and AIDS-related patients who had been
      admitted to TM Jafferji Hospital, Dar-es-Salaam, Tanzania. METHODS: Proven cases
      of HIV were recruited in this study. Detailed slit lamp examination and
      fundoscopy using a +90D lens were carried out in all cases after thoroughly
      dilating the pupil with 1% Tropicamide eye drops. RESULTS: Around 90% of the
      recruited cases were in clinical stage III and IV HIV. The notable ocular
      manifestations included micro-vasculopathy of the retina in 25%, uveitis in 8%,
      CMV retinitis in 7%, neuro-ophthalmic manifestation in 6%, Herpes zoster
      ophthalmicus in 5%, Kaposi's sarcoma in 3% and conjunctival carcinoma in 2% of
      cases. Fifty-three percent of the cases had other anterior segment disorders like
      conjunctivitis, blepharitis and corneal ulcers. CONCLUSION: Most of the cases
      recruited in our study were in the late stages of HIV. A significantly high
      number of cases (70%) had ocular manifestations. Around 53% had additional
      anterior segment disorders like conjunctivitis, blepharitis and corneal ulcers.

PMID- 22135521
TI  - Assessing patient pain scores in the emergency department.
AB  - BACKGROUND: Pain management in the Emergency Department is challenging. Do we
      need to ask patients specifically about their pain scores, or does our
      observational scoring suffice? The objective of this study was to determine the
      inter-rater differences in pain scores between patients and emergency healthcare
      (EHC) providers. Pain scores upon discharge or prior to ward admission were also
      determined. METHODS: A prospective study was conducted in which patients
      independently rated their pain scores at primary triage; EHC providers (triagers
      and doctors) separately rated the patients' pain scores, based on their
      observations. RESULTS: The mean patient pain score on arrival was 6.8 +/- 1.6,
      whereas those estimated by doctors and triagers were 5.6+/-1.8 and 4.3+/-1.9,
      respectively. There were significant differences among patients, triagers and
      doctors (P< 0.001). There were five conditions (soft tissue injury, headache,
      abdominal pain, fracture and abscess/cellulites) that were significantly
      different in pain scores between patients and EHC providers (P<0.005). The mean
      pain score of patients upon discharge or admission to the ward was 3.3 +/- 1.9.
      CONCLUSIONS: There were significant differences in mean patient pain scores on
      arrival, compared to those of doctors and triagers. Thus, asking for pain scores
      is a very important step towards comprehensive pain management in emergency
      medicine.

PMID- 22135522
TI  - Treatment outcome of superficial cerebral abscess: an analysis of two surgical
      methods.
AB  - BACKGROUND: The purpose of the study is to compare the two surgical methods (burr
      hole and craniotomy) used as treatment for superficial cerebral abscess and its
      outcome in terms of radiological clearance on brain CT, improvement of
      neurological status, the need for repeated surgery, and survival and morbidity at
      three months after surgery. This report is a retrospective case review of the
      patients who were treated surgically for superficial cerebral abscess in Hospital
      Kuala Lumpur (HKL) and Hospital Sultanah Aminah (HSA) over a period of four years
      (2004 to 2007). METHODS: Fifty-one cases were included in this study: 64.7% of
      patients were male and 35.5% were female. Most of the patients were Malay
      (70.6%); 28 patients (54.9%) had undergone craniotomy and excision of abscess,
      and the rest had undergone burr hole aspiration as their first surgical
      treatment. RESULTS: This study reveals that patients who had undergone craniotomy
      and excision of abscess showed a significantly earlier improvement in
      neurological function, better radiological clearance and lower rate of re-surgery
      as compared to the burr hole aspiration group (P<0.05). However, with respect to
      neurological improvement at 3 months, morbidity and mortality, there is no
      significant difference between the two surgical methods. CONCLUSION: The
      significance of these findings can only be confirmed by a prospective randomised
      series. Further study will be required to assess the cost effectiveness,
      intensive care needs, and possibility of shorter antibiotic usage as compared to
      burr hole aspiration.

PMID- 22135523
TI  - Prevalence and Sources of Stress among Universiti Sains Malaysia Medical
      Students.
AB  - BACKGROUND: Being in medical school has always been regarded as highly stressful.
      Excessive stress causes physical and mental health problems. Persistent stress
      can impair students' academic achievement and personal or professional
      development. The aim of this study is to explore the nature of stress among
      medical students by determining the prevalence, sources and pattern of stress and
      the factors affecting it. METHODS: We chose a cross-sectional study design
      utilizing validated questionnaires, the 12 items General Health Questionnaire
      (GHQ-12) and Medical Student Stressor Questionnaire (MSSQ), to evaluate stress
      levels and stressors. School and ethical committee clearance were obtained prior
      to the study. Data were analysed using SPSS version 12. RESULTS: Of the medical
      students who were administered the questionnaire, 761 (72%) respondents
      participated in this study. The prevalence of stress among the medical students
      was 29.6%. The top 10 stressors were academic-related. Prevalence of stress for
      the first, second, third, fourth and fifth year students was 26.3%, 36.5 %,
      31.4%, 35.3% and 21.9%, respectively. Year of study was the only significant
      factor affecting stress among medical students (P-value < 0.05). CONCLUSIONS: The
      prevalence of stress among medical students in USM is high. Academic-related
      problems were the major stressor among medical students. Year of study was the
      factor most significantly associated with medical students' stress. There was a
      bimodal pattern of the stress level throughout the year of study.

PMID- 22135524
TI  - A study on the magnitude and the effectiveness of the observation ward of
      hospital universiti sains malaysia.
AB  - BACKGROUND: The observation ward (OW) allows patients to be reassessed and
      monitored before deciding either to admit or to discharge them. This is a six
      month descriptive cross-sectional study conducted in the observation ward of the
      Emergency Department (ED) of Hospital Universiti Sains Malaysia, Kelantan. The
      objective of this study was to examine the demographic characteristics and
      clinical profiles of adult observed patients and to determine the effectiveness
      of OW management. METHODS: Patients were selected randomly by convenience
      sampling. One hundred and twenty-four patients were included in the study. The
      mean age was 40.3 +/- 18.5 years (95% CI: 37.2 to 43.8). RESULTS: Among the
      common clinical problems were abdominal discomfort (23%), diarrhoea and vomiting
      (13%) and fever (13%). Reasons for OW admission included diagnostic uncertainty
      (63%) and short course of treatment (33%). The mean length of stay was 4.1 +/-
      1.8 hours (95% CI=3.8 to 4.4 hours). Most of the patients (85%) were discharged.
      CONCLUSIONS: The OW of HUSM is effective in managing adult patients as determined
      by the hospitalisation rate and the length of stay.

PMID- 22135525
TI  - Angioarchitecture of brain arteriovenous malformations and the risk of bleeding:
      an analysis of patients in northeastern malaysia.
AB  - BACKGROUND: Central nervous system arteriovenous malformation (AVM) is a vascular
      malformation of the brain and involves entanglement of veins and arteries without
      an intervening capillary bed. Affecting predominantly young male patients, AVM
      presents with different clinical manifestations namely headache, seizures,
      neurological deficit and intracranial haemorrhage. The patients who present
      acutely with intracranial bleeding have a significant morbidity and mortality.
      The aim is to study the angioarchitecture of brain AVM (BAVM) and determine the
      risk factors for intracranial bleeding. Ultimately, the goal of the study is to
      look for the association between volume of haematoma and architecture of BAVM.
      METHODS: A cross-sectional study of 58 patients was conducted at the Hospital
      Universiti Sains Malaysia. Data were collected over a period of seven years (2000
      to 2007) to look for the association between the angioarchitecture of brain
      arteriovenous malformations (BAVM), haemodynamics and the natural history and
      risk of intracranial haemorrhage. RESULTS: BAVM was predominantly found in young
      male patients in 65.5%. Small nidal size (P-value=0.004), deep location (P
      value=0.003) and deep venous drainage (P-value=0.006) were found to be
      significant factors contributing to intracranial haemorrhage. All patients with
      coexisting intranidal or prenidal aneurysms presented with intracranial
      haematoma. CONCLUSION: The angioarchitecture of BAVM like nidal size, deep
      location and deep venous drainage can predict the risk of intracranial bleeding
      and can help in the management of high risk patients without any delay. Small
      sized and deep seated lesions have a diffuse type of intracranial bleed which
      eventually need more attention to the managing team as diffuse haematoma
      indicates more insult to brain.

PMID- 22135526
TI  - Phonophobia and hyperacusis: practical points from a case report.
AB  - Phonophobia and hyperacusis are two separate but closely related symptoms that
      are often mistakenly used in clinical practice as the same entity. Here we
      present a case report to highlight the distinguishing features of both and
      discuss the steps of management in these conditions. It is vital for the
      attending doctors to recognise hyperacusis and phonophobia as different entities
      to manage them successfully.

PMID- 22135527
TI  - An unexpected cause of hoarseness of voice in a healthy teenager.
AB  - Laryngeal amyloidosis is a rare cause of stridor in a healthy young adult. We
      report a case of localised laryngeal amyloidosis, including our MRI findings,
      which included a necrotic centre that has not previously been described. This
      case also highlights the need for a high index of clinical suspicion to achieve
      the correct histopathological interpretation.

PMID- 22135528
TI  - Endoscopic-assisted Enucleation of Radicular Cysts - A Case Report.
AB  - The standard management for the majority of benign jaw cysts is enucleation,
      marsupialisation, curettage and decompression. Enucleation has the advantage that
      the whole specimen is sent for microscopic evaluation so that more sinister
      pathological processes (i.e. squamous cell carcinoma) may not be missed. In a
      large cystic lesion, enucleation is still possible, but technical difficulties
      might be encountered. In such instances, inevitable damage can occur to the
      surrounding structures. We report a case of a large radicular cyst of the maxilla
      that was enucleated via endoscopic assistance through the Caldwell Luc approach.

PMID- 22135530
TI  - Brain in business: the economics of neuroscience.

PMID- 22135529
TI  - Scalene myofascial pain syndrome mimicking cervical disc prolapse: a report of
      two cases.
AB  - Scalene myofascial pain syndrome is a regional pain syndrome wherein pain
      originates over the neck area and radiates down to the arm. This condition may
      present as primary or secondary to underlying cervical pathology. Although
      scalene myofascial pain syndrome is a well known medical entity, it is often
      misdiagnosed as being some other neck pain associated with radiculopathy, such as
      cervical disc prolapse, cervical spinal stenosis and thoracic outlet syndrome.
      Because scalene myofascial pain syndrome mimics cervical radiculopathy, this
      condition often leads to mismanagement, which can, in turn, result in persistent
      pain and suffering. In the worst-case scenarios, patients may be subjected to
      unjustifiable surgical intervention. Because the clinical findings in scalene
      myofascial pain syndrome are "pathognomonic", clinicians should be aware of ways
      to recognize this disorder and be able to differentiate it from other conditions
      that present with neck pain and rediculopathy. We present two cases of unilateral
      scalene myofascial pain syndrome that significantly impaired the patients'
      functioning and quality of life. This case report serves to create awareness
      about the existence of the syndrome and to highlight the potential morbidity due
      to clinical misdiagnosis.

PMID- 22135531
TI  - Observation of ureteric diameter in negative intravenous urogram in hospital
      universiti kebangsaan malaysia.
AB  - BACKGROUND: This study observed the widest ureteric diameter in negative
      intravenous urogram (IVU) examinations using low osmolar contrast media. METHODS:
      We reviewed a total of one hundred and eighty four ureters from 92 negative IVUs.
      RESULTS: The results show a mean diameter for the abdominal ureter of 4.19 mm
      with an SD of 1.27 mm and a mean pelvic ureteric diameter of 4.45 mm with an SD
      of 1.37 mm. The upper limits for abdominal ureter and pelvic ureter based on a
      confidence interval of 95% were 4.37 mm and 4.64 mm, respectively. CONCLUSIONS:
      There was no significant difference between the right and left ureteric diameter
      in both female and male subjects. There was no significant correlation between
      ureteric diameters and the age of subjects, from the second to the eighth
      decades.

PMID- 22135532
TI  - Preventing HIV Transmission in Nigeria: Role of the Dentists.
AB  - BACKGROUND: As healthcare providers, dentists are in a unique position to foster
      behavioural changes that are needed to stem the spread of HIV infection. This
      study was conducted to assess the role of dentists in the prevention of HIV
      transmission in Nigeria. METHODS: This descriptive cross-sectional survey was
      conducted from June 2006 to January 2007. A multi-stage sampling technique was
      used to select 300 practising dentists from all parts of Nigeria. Data were
      collected through a self-administered questionnaire that focused on dentist
      demographic details, attitudes towards treating HIV-infected persons, involvement
      in public or clinic-based patient education on HIV and infection control.
      RESULTS: Two hundred and fifty-seven questionnaires were returned completed,
      constituting an 86% response rate. The majority of respondents (77.8%) had their
      dental practice in the southern part of Nigeria, and 89% were in the age bracket
      of 21-40 years. HIV education by dentists was ranked as poor, as less than a
      quarter of respondents routinely educated patients on HIV in the clinic. Only a
      few dentists (33.3%) were involved in public enlightenment programme on HIV in
      the previous 12 months. Most of the respondents (93%) reported a willingness to
      treat HIV-infected patients while observing universal precautions. Good infection
      barrier practices were adopted by 89.9% of dentists, and disposable cartridges
      for local anaesthetic agents and dental needles were not reused by 93.4% of the
      respondents. Autoclaving was the most widely used sterilization method (73.2%),
      but less than half of the respondents knew how to ascertain whether sterilization
      was effective. CONCLUSION: This study revealed that efforts by Nigerian dentists
      to prevent HIV transmission are presently less than optimal. Therefore, there is
      a need for sensitisation and motivation through seminars, workshops and lectures.

PMID- 22135533
TI  - The Prevalence of Urinary Incontinence among the Elderly in a Rural Community in
      Selangor.
AB  - BACKGROUND: Urinary incontinence is a common but poorly understood problem in the
      elderly population. The aim of this study was to determine the prevalence of
      urinary incontinence and its associated factors among the elderly in a community
      setting. METHODS: A cross-sectional study design was used. Stratified cluster
      sampling was used in this study. All elderly residents aged 60 years old and
      above who fulfilled the selection criteria were included as respondents. The
      translated Malay version of the Barthel's Index (BI) was used to identify the
      presence of urinary incontinence. RESULTS: The prevalence of urinary incontinence
      was 9.9% among the elderly respondents. Urinary incontinence among the elderly
      was significantly associated with age, gender, depression, functional dependence,
      and diabetes mellitus (P < 0.05).

PMID- 22135534
TI  - Effect on Antioxidant Levels in Patients of Breast Carcinoma during Neoadjuvant
      Chemotherapy and Mastectomy.
AB  - BACKGROUND: Breast cancer is the most common cancer in Indian women. The aim of
      this study was to assess the levels of red blood cell (RBC) superoxide dismutase
      (r-SOD), RBC catalase (r-CAT), RBC glutathione peroxidase (r-GPx) and the ferric
      reducing ability of plasma (FRAP) in advanced breast cancer patients post
      mastectomy before and after chemotherapy. METHODS: Female breast cancer patients
      between 27 and 65 years of age who were admitted to the Department of Surgery of
      the All India Institute of Medical Sciences in New Delhi were enrolled in the
      study. This study included two arms: a control group of healthy age-matched
      females (n=20) and patients undergoing treatment with a combination of the
      anticancer drugs cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) (n=55),
      No treatment was given to the control group. The CAF group received CAF treatment
      at weeks 0, 3, and 6, then surgery at week 9 followed by CAF treatment at weeks
      12, 15, and 18. A three-week drug-free interval was included between each cycle
      of drug treatment. Blood samples were collected from control subjects and from
      patients in the CAF group before administration of drugs at week zero to
      establish a baseline, again weeks 12 and 18, and once more at the end of the 26
      week treatment. Blood samples collected from the control subjects and CAF
      patients were analysed to determine levels of the endogenous antioxidants, r-SOD,
      r-CAT, r-GPx, and FRAP. RESULTS: Levels of r-SOD, r-CAT, r-GPx, and FRAP in CAF
      treated patients at 12, 18, and 26 weeks were significantly decreased (P<0.001)
      in comparison to the baseline levels observed at week zero. CONCLUSION: The
      results from the present study show that a change in the enzyme antioxidant
      systems in patients after chemotherapy and mastectomy causes an overall decrease
      in antioxidant levels. Chemotherapeutic agents induce oxidative stress that
      damages many cellular targets.

PMID- 22135535
TI  - Computed Tomography (CT) Imaging of Injuries from Blunt Abdominal Trauma: A
      Pictorial Essay.
AB  - Blunt abdominal trauma can cause multiple internal injuries. However, these
      injuries are often difficult to accurately evaluate, particularly in the presence
      of more obvious external injuries. Computed tomography (CT) imaging is currently
      used to assess clinically stable patients with blunt abdominal trauma. CT can
      provide a rapid and accurate appraisal of the abdominal viscera, retroperitoneum
      and abdominal wall, as well as a limited assessment of the lower thoracic region
      and bony pelvis. This paper presents examples of various injuries in trauma
      patients depicted in abdominal CT images. We hope these images provide a resource
      for radiologists, surgeons and medical officers, as well as a learning tool for
      medical students.

PMID- 22135536
TI  - Outcome of neonatal hyperbilirubinemia in a tertiary care hospital in bangladesh.
AB  - BACKGROUND: Kernicterus occurs in infants around the world. This study examined
      the outcomes of various treatments for neonatal hyperbilirubinemia (NH) used in
      the Khulna Medical College Hospital in Bangladesh. METHODS: All of the jaundiced
      newborns in the neonatal ward between 2005 and 2008 were included in the study.
      Total serum bilirubin and fractional levels were measured in all cases,
      regardless of the degree of jaundice. NH was classified as mild, moderate or
      severe depending on the bilirubin level; mild NH was treated with a sunbath,
      moderate NH was treated with phototherapy, and severe NH was treated with
      exchange transfusion. RESULTS: Of 1981 neonates, 426 (22%) were diagnosed with
      NH. Physiological jaundice (26.7%) was most common, followed by the jaundice of
      prematurity (20.9%). Haemolytic jaundice was primarily caused by ABO
      incompatibility (11.3%) and Rh incompatibility (5.4%). Exchange transfusion (ET)
      was performed in 22 patients; four (18.2%) died as a result of hazards that could
      have been avoided with skilled monitoring. Twelve (2.8%) individuals with
      jaundice died. Kernicterus developed in nine (2.1%) children, four of whom
      survived with neurological sequelae. CONCLUSION: ABO incompatibility is twice as
      common as Rh incompatibility. The majority of kernicterus patients died in the
      acute phase.

PMID- 22135537
TI  - Gastric schwannoma in a female patient with pulmonary tuberculosis - a
      clinicopathological assessment and diagnosis.
AB  - Schwannomas, or neurinomas, are generally benign, slow-growing, asymptomatic
      neoplasms originating from the Schwann cells of a nerve sheath. As a part of
      spindle cell mesenchymal tumours, schwannomas arising from the gastrointestinal
      tract (GIT) are unusual; however, when they occur, the most common site involved
      is the stomach, which represents 0.2% of all gastric tumours. We report the case
      of a 35-year-old female patient with a history of pulmonary tuberculosis
      presenting with a large palpable abdominal mass reaching up to the peritoneal
      cavity. The initial clinical impression was a tuberculous abdominal mass, a cyst,
      or a teratoma. However, intra-operative findings during a subtotal gastrectomy
      revealed an exophytic gastric serosal mass, which suggested a gastrointestinal
      stromal tumour (GIST). Post-operative histopathological findings showed a
      fascicular arrangement of neoplastic spindle cells with pallisading nuclei that
      showed intense positivity for S-100 protein, and were negative for CD117 and
      desmin in immunohistochemistry studies. These results confirmed the final
      diagnosis of a gastric schwannoma.

PMID- 22135538
TI  - Necrotizing fasciitis of the head and neck: surgical outcomes in three cases.
AB  - Necrotizing fasciitis of the head and neck is a rare, rapidly progressive
      infection involving the skin, subcutaneous tissue and fascia. We report three
      cases of necrotizing fasciitis that differ in their presentation and outcome. The
      first case involves a patient who presented with progressively enlarging anterior
      neck swelling that was later complicated by dehydration and reduced
      consciousness. The second case is a patient with neck swelling and ipsilateral
      otorrhea. The third case concerns a patient with a buccal ulcer complicated by
      ipsilateral facial swelling. All of them underwent a fasciotomy with wound
      debridement with the addition of a cortical mastoidectomy in the second case. Two
      of these patients recovered well. Unfortunately, the third case succumbed to
      death due to airway compromise and septicaemia. We advocate the importance of
      eradicating the source of infection followed by frequent, meticulous wound
      dressing and strict blood sugar control to obtain better outcomes in managing
      necrotizing fasciitis of the head and neck. However, involvement of the airway
      carries a grave prognosis despite aggressive treatment.

PMID- 22135539
TI  - Bilateral vocal cord palsy as the sole presentation of acquired syphilis.
AB  - Bilateral vocal cord palsy is almost always caused by neck surgery, particularly
      surgery of the thyroid. We report a case of bilateral vocal cord palsy requiring
      emergency surgery to relieve the airway obstruction as the sole presentation of
      acquired syphilis. As the incidence of syphilis worldwide is rising, this unusual
      presentation may give clinicians a different perspective on the disease.

PMID- 22135540
TI  - Ketamine-associated ulcerative cystitis: a case report and literature review.
AB  - Ketamine can be abused as a recreational drug, and there has been a recent surge
      in its usage. The effects of ketamine on the urinary system were unknown until
      the recent publication of a few case reports. Many doctors are still unaware of
      this new clinical entity, termed ketamine-associated ulcerative cystitis. We
      report a case that we encountered and discuss the diagnosis and disease
      management in addition to a review of the literature.

PMID- 22135541
TI  - Antibody mediated immunity - a missed opportunity in the fight against
      tuberculosis?

PMID- 22135542
TI  - The Confluence Between Arts and Medical Science - Music and movement therapy for
      children with Cerebral Palsy.

PMID- 22135544
TI  - Lycopersicon esculentum (Tomato) Prevents Adverse Effects of Lead on Blood
      Constituents.
AB  - BACKGROUND: Lead is known for its adverse effects on various organs and systems.
      In this study, the ability of lead to adversely affect blood parameters was
      investigated, and Lycopersicon esculentum, or commonly known as tomato (a source
      of antioxidants), was administered orally in the form of tomato paste (TP) to
      reduce the adverse effects of lead. METHODS: The study involved 56 Wistar rats
      divided equally into 4 groups of 14 rats each: Control, LA(G), TP(G), and
      LA+TP(G). Control and TP(G) rats were given distilled water ad libitum, while
      LA(G) and LA+TP(G) rats were given 1% lead (II) acetate (LA) per day. TP(G) and
      LA+TP(G) rats were additionally treated with 1.5 ml of TP per day. All treatments
      lasted for 10 weeks, after which the rats were weighed and sacrificed, and
      haematological and biochemical parameters were measured. The independent samples
      t test was used to analyse the results. RESULTS: LEAD CAUSED SIGNIFICANT
      REDUCTIONS IN THE FOLLOWING PARAMETERS: weight; packed cell volume; red blood
      cell and white blood cell counts; the percentages of lymphocytes and monocytes;
      total serum protein, albumin, and globulin levels; and plasma superoxide
      dismutase and catalase activities. In contrast, lead caused a significant
      increase in the percentage of neutrophils and the plasma malondialdehyde
      concentration. TP, however, significantly prevented the adverse effects of LA.
      CONCLUSION: The oral administration of TP prevents the adverse effects of lead on
      blood constituents.

PMID- 22135543
TI  - Genetic aberrations in childhood acute lymphoblastic leukaemia: application of
      high-density single nucleotide polymorphism array.
AB  - Screening of the entire human genome using high-density single nucleotide
      polymorphism array (SNPA) has become a powerful technique used in cancer genetics
      and population genetics studies. The GeneChip(r) Mapping Array, introduced by
      Affymetrix, is one SNPA platform utilised for genotyping studies. This GeneChip
      system allows researchers to gain a comprehensive view of cancer biology on a
      single platform for the quantification of chromosomal amplifications, deletions,
      and loss of heterozygosity or for allelic imbalance studies. Importantly, this
      array analysis has the potential to reveal novel genetic findings involved in the
      multistep development of cancer. Given the importance of genetic factors in
      leukaemogenesis and the usefulness of screening the whole genome, SNPA analysis
      has been utilised in many studies to characterise genetic aberrations in
      childhood acute lymphoblastic leukaemia.

PMID- 22135545
TI  - Correlation of Nuclear Morphometry and AgNOR Score with Radiation Response in
      Squamous Cell Cancers of the Head and Neck: A Preliminary Study.
AB  - BACKGROUND: Prediction of radiation response before the completion of the
      radiotherapy schedule is challenging. Information about radiation response could
      help oncologist to choose the appropriate combination and sequence of therapies
      in the multidisciplinary management of cancer. METHODS: The study involved 26
      patients with squamous cell cancers of the head and neck region who received
      radiotherapy to a dose of 30 Gy in 10 fractions over a 2-week period as part of a
      split-course technique. Fine-needle aspiration cytology was performed on day 1
      and day 5 of the schedule. The silver staining of the nuclear organiser region
      (AgNOR) and nuclear morphometric study were done on both days. RESULTS: The
      median age of the patients was 44 years old. The primary tumours were distributed
      in the nasopharynx (n = 11), larynx and hypopharynx (n = 5), metastatic node (n =
      4), and miscellaneous tumours were found in the head and neck sub sites (n = 6).
      The mean initial AgNOR score was 3.0, range 1.2-7.0. The median of nuclear and
      nucleolar diameters were 11.07 MUm, range 7.70-16.6 MUm, and 2.92 MUm, range 1.09
      11.66 MUm, respectively. Patients with a pre-radiotherapy AgNOR score of greater
      than 2.5 were associated with disease progression and metastasis. However, the
      increased of nuclear diameter on day 5 compared with baseline predicted a good
      radiation response in patients (P = 0.016). CONCLUSION: Intra-radiotherapy
      nuclear morphometry combined with baseline AgNOR score could be a simple and
      useful tool for the prediction of radiation response in head and neck cancers.

PMID- 22135546
TI  - The effect of delayed transportation of blood samples on serum bilirubin values
      in neonates.
AB  - BACKGROUND: Delays in transporting blood samples may cause inaccurate results.
      Samples may be exposed to light or heat during delays, resulting in the
      degradation of analytes, for example, bilirubin. This study was done to determine
      the effect of delays in the transportation of blood samples on serum bilirubin
      test results. METHODS: Samples taken from neonates admitted to a tertiary
      hospital with jaundice were included in the study. The samples were collected
      through venipuncture in 3 labelled containers. The first container was sent
      immediately to the laboratory, while the second and third containers were sent
      after being kept in the ward for 1 and 3 hours, respectively. Bilirubin values
      were measured colourimetrically at a wavelength of 578 nm using a Roche Hitachi
      912 Chemistry Analyser upon arrival in the laboratory. RESULTS: A total of 36
      serum samples were studied. The mean of the indirect bilirubin measurements for 0
      , 1-, and 3-hour samples were 174 (SD 68.65), 186.97 (SD 60.47), and 184.56 (SD
      66.93), respectively. There was a significant difference in the mean indirect
      bilirubin measurement of 1-hour samples (P = 0.047, 95% CI -24.66 to -1.18) and 3
      hour samples (P = 0.045, 95% CI -19.77 to -0.23) compared with 0-hour samples.
      There were no significant differences observed in either the mean total bilirubin
      or the mean direct bilirubin measurements of different time intervals.
      CONCLUSION: This study confirms that delays in the transportation of blood
      samples influence the bilirubin test results.

PMID- 22135547
TI  - Reliability and validity of a Malay-version questionnaire assessing knowledge of
      breastfeeding.
AB  - BACKGROUND: There is a need to identify the knowledge that mothers have about
      breastfeeding to help promote it. Therefore, it is important to develop a valid
      and reliable questionnaire to provide useful and comparable data about
      breastfeeding knowledge. The objectives of this study were to determine the
      reliability and validity of a Malay version of a questionnaire assessing
      breastfeeding knowledge and describe the breastfeeding knowledge level among
      respondents. METHODS: A cross-sectional study was conducted from 1 January to 31
      May 2008 among female staff working at the Universiti Sains Malaysia Health
      Campus. A self-administered questionnaire containing 53 items assessing
      breastfeeding knowledge was given to respondents. The questions were adapted and
      modified from a breastfeeding questionnaire developed by a team of Hospital
      Universiti Sains Malaysia paediatric nurses. Exploratory factor analysis,
      internal consistency reliability, and descriptive analysis of respondents'
      knowledge were conducted. RESULTS: A total of 252 female staff participated in
      the study. Factor analysis constructed 10 domains of knowledge and excluded 6
      items, leaving 47 items in the final questionnaire. Cronbach's alpha of the final
      questionnaire was 0.77. Respondents' lowest knowledge was on the practical
      aspects of breastfeeding. CONCLUSION: The questionnaire is reliable and valid to
      assess the breastfeeding knowledge of Malaysian women.

PMID- 22135548
TI  - Big Sib Students' Perceptions of the Educational Environment at the School of
      Medical Sciences, Universiti Sains Malaysia, using Dundee Ready Educational
      Environment Measure (DREEM) Inventory.
AB  - BACKGROUND: A cross-sectional descriptive study was conducted among Big Sib
      students to explore their perceptions of the educational environment at the
      School of Medical Sciences, Universiti Sains Malaysia (USM) and its weak areas
      using the Dundee Ready Educational Environment Measure (DREEM) inventory. The
      DREEM inventory is a validated global instrument for measuring educational
      environments in undergraduate medical and health professional education. METHOD:
      The English version of the DREEM inventory was administered to all Year 2 Big Sib
      students (n = 67) at a regular Big Sib session. The purpose of the study as well
      as confidentiality and ethical issues were explained to the students before the
      questionnaire was administered. RESULTS: The response rate was 62.7% (42 out of
      67 students). The overall DREEM score was 117.9/200 (SD 14.6). The DREEM
      indicated that the Big Sib students' perception of educational environment of the
      medical school was more positive than negative. Nevertheless, the study also
      revealed some problem areas within the educational environment. CONCLUSION: This
      pilot study revealed that Big Sib students perceived a positive learning
      environment at the School of Medical Sciences, USM. It also identified some low
      scored areas that require further exploration to pinpoint the exact problems. The
      relatively small study population selected from a particular group of students
      was the major limitation of the study. This small sample size also means that the
      study findings cannot be generalised.

PMID- 22135549
TI  - The risk factors of external ventricular drainage-related infection at hospital
      kuala lumpur: an observational study.
AB  - BACKGROUND: External ventricular drainage (EVD) has been widely used for the
      purpose of cerebrospinal fluid (CSF) diversion at Hospital Kuala Lumpur (HKL).
      METHOD: This prospective observational study was conducted in HKL from December
      2006 to December 2008 among patients who were subjected for EVD, following strict
      inclusion and exclusion criteria. RESULTS: The frequency of EVD-related infection
      was as high as 32.2% (95% CI 23.3% to 42.57%) among 87 patients studied. This
      study clearly demonstrates that tunnelling the catheter for more than 5 cm under
      the scalp, from the burr hole to the exit site of the skin, carried a
      significantly lower risk of infection compared with tunnelling the catheter for 5
      cm or less (OR = 0.184, 95% CI 0.083 to 0.406, P < 0.001). The majority of cases
      (19 out of 28) with EVD-related infection occurred among patients catheterised
      for more than 10 days (OR = 0.334, 95% CI 0.171 to 0.652, P < 0.001). CONCLUSION:
      The technique of subgaleal tunnelling of more than 5cm and the duration of the
      ventricular catheterisation of 10 days and less should be implemented as
      standardised protocol at health institutions to reduce the risk of EVD-related
      infections.

PMID- 22135550
TI  - Embolisation of a bronchial artery of anomalous origin in massive haemoptysis.
AB  - Massive haemoptysis is the most dreaded of all respiratory emergencies. Bronchial
      artery embolisation is known to be a safe and effective procedure in massive
      haemoptysis. Bronchial artery of anomalous origin presents a diagnostic challenge
      to interventional radiologists searching for the source of haemorrhage. Here, we
      report a case of massive haemoptysis secondary to a lung carcinoma with the
      bronchial artery originating directly from the right subclavian artery. This
      artery was not evident during the initial flush thoracic aortogram. The anomalous
      origin bronchial artery was then embolised using 15% diluted glue with good
      results. An anomalous-origin bronchial artery should be suspected if the source
      of haemorrhage is not visualised in the normally expected bronchial artery
      location.

PMID- 22135551
TI  - Atretic cephalocele - an uncommon cause of cystic scalp mass.
AB  - A 6 year-old girl presented with a midline parietal scalp swelling that had been
      gradually enlarging since birth. Magnetic resonance imaging revealed
      communication of the cyst with the subarachnoid space through a calvarial defect,
      with concomitant findings of vertically positioned straight venous sinus and
      subependymal grey matter heterotopia. A diagnosis of atretic cephalocele was thus
      made based on these classical imaging findings.

PMID- 22135552
TI  - Migration of the abdominal catheter of a ventriculoperitoneal shunt into the
      mouth: a rare presentation.
AB  - A 1-year-old boy with a history of exomphalos and hydrocephalus had surgeries to
      correct these pathologies. The ventriculopleural (VP(L)) shunt inserted for
      hydrocephalus was complicated by pleural effusion, for which a
      ventriculoperitoneal (VP) shunt was inserted on the contralateral side. He
      subsequently presented with protrusion of the distal VP shunt tip from the mouth
      due to perforation through the gastrointestinal tract. The child also had a
      history of peritonitis post-exomphalos repair, which may have predisposed him to
      this relatively uncommon shunt complication. Probable causes and risk factors of
      the perforation are discussed.

PMID- 22135553
TI  - Two cases of congenital vallecular cyst: a reminder of the potentially fatal
      cause of upper airway obstruction in infants.
AB  - Vallecular cyst, a benign yet rare laryngeal lesion, may cause stridor and even
      life-threatening upper airway obstruction in infants. It can cause apnoea and
      poor feeding habits, thus reducing the chance of survival. Although
      laryngomalacia remains the most common cause of stridor in this age group,
      awareness and a high level of suspicion for this condition can help lead to early
      management and intervention. Direct laryngoscopy is accepted as the gold standard
      for diagnostic purposes, and marsupialisation of the cyst is the preferred
      treatment. We describe 2 cases of vallecular cysts in infants admitted to our
      hospital where timely diagnoses led to appropriate treatment.

PMID- 22135554
TI  - Troponin-keep up or be left behind.

PMID- 22135555
TI  - Evaluation of the antidiabetic and antilipaemic activities of the hydroalcoholic
      extract of phoenix dactylifera palm leaves and its fractions in alloxan-induced
      diabetic rats.
AB  - BACKGROUND: The antidiabetic and antilipaemic effects of Phoenix dactylifera leaf
      extract (PDE) and its fractions were investigated in various rat models. METHODS:
      Diabetes was induced in male Wistar rats by alloxan monohydrate. Diabetic animals
      were randomly divided into 8 groups (1 diabetic control and 7 treated groups).
      Diabetic control animals received saline (5 mL/kg) orally, whereas the treatment
      groups received different doses of PDE (100, 200, and 400 mg/kg), PDE fractions
      (50, 100, and 200 mg/kg), or glibenclamide (4 mg/kg) orally once a day for 14
      days. Blood was withdrawn for glucose determination on the 1(st), 6(th), 10(th),
      and 14(th) days. The rats were fasted overnight and then sacrificed on the 14(th)
      day; blood was collected for biochemical evaluation, including the levels of
      blood glucose, plasma insulin, serum triglyceride, and cholesterol. RESULTS:
      Subacute administration of PDE or its fractions in alloxan-induced diabetic rats
      significantly reduced blood glucose (P < 0.01). Water intake, serum triglyceride,
      and cholesterol also decreased in treated animals compared with the control group
      (P < 0.01). Plasma insulin level increased in the treated groups relative to the
      control group (P < 0.01). CONCLUSION: The results suggested that PDE exhibits
      antidiabetic and antilipaemic effects in alloxan-induced diabetic rats.

PMID- 22135556
TI  - Abnormal microvascular reactivity with hypercholesterolaemia in pregnancy.
AB  - BACKGROUND: Post-occlusive skin reactive hyperaemia (PORH) is a model used to
      assess microvascular reactivity. This study aims to compare PORH response among
      pregnant hypercholesterolaemic patients with age and gestational age-matched
      controls. METHODS: This cross sectional study involved 17 hypercholesterolaemic,
      pregnant women and 20 pregnant controls entering their early third trimester.
      Laser Doppler fluximetry (LDF) was used to measure skin perfusion. The process of
      PORH was performed by occluding the upper arm with an occlusion cuff at 200 mmHg
      for 3 minutes. Skin perfusion was recorded before, during, and after occlusion
      release. Baseline perfusion, time to achieve peak perfusion (Tp), peak perfusion
      after occlusion release (PORH(peak)), and maximum change in perfusion due to
      occlusion (PORH(max)) were recorded. RESULTS: Serum total cholesterol (TC) was
      significantly different (P < 0.001) between the 2 groups: 7.25 (SEM 0.18) mmol/L
      for hypercholesterolaemic women and 5.54 (SEM 0.15) mmol/L for the control group.
      There were no significant differences in their baseline, PORH(peak), and
      PORH(max). However, Tp in the hypercholesterolaemic group was significantly
      increased (P = 0.024) compared with the controls at 14.9 (SEM 0.6) seconds and
      13.1 (SEM 0.5) seconds, respectively. CONCLUSION: Pregnant hypercholesterolaemic
      patients showed an abnormal microvascular reactivity response. Tp with ischemia
      was significantly increased compared with normocholesterolaemic controls.

PMID- 22135557
TI  - Hyperendemicity of onchocerciasis in ovia northeast local government area, edo
      state, Nigeria.
AB  - BACKGROUND: Onchocerciasis is a chronic parasitic infection caused by the
      filarial nematode, Onchocerca volvulus. The objective of this study was to
      determine the prevalence, endemicity, and symptomatic effects of the disease in
      Ovia Northeast Local Government Area. METHODS: The prevalence of onchocerciasis
      was investigated in Ovia Northeast Local Government Area of Edo State, Nigeria,
      between March 2008 and June 2009 using the standard skin-snip method. A total of
      2020 subjects, who had visited various primary health centres located in each
      community, were enlisted using randomised sampling, and the data were analysed
      using the Chi-squared (chi(2)) test and logistic regression. RESULTS: A Of the
      2020 individuals examined, 1674 (83%) harboured microfilaria in their skin
      tissues. On the basis of the standardised scale for microfilaria prevalence-less
      than 10% is considered sporadic, 10%-29% is considered hypoendemic, 30%-59% is
      considered mesoendemic, and 60% and above is considered hyperendemic-the
      prevalence (83%) reported in this study led to the disease being classified as
      hyperendemic. Females were more frequently infected than were males, and this was
      statistically significant (P < 0.001). Prevalence was also found to increase with
      age, and this correlation was significant (P < 0.001). The prevalence of the
      clinical features of the disease in the local government area was 87.5% for
      leopard skin, 84.16% for itching, and 75.42% for nodules. CONCLUSION: A
      prevalence of 83% was observed and considered hyperendemic. Female gender and age
      (50 years or more) were significant risk factors that affected the prevalence of
      onchocerciasis. The findings demonstrated the hyperendemicity of infection and
      the need for urgent attention with ivermectin treatment and other control
      measures.

PMID- 22135558
TI  - A three-dimensional computed tomography analysis of craniofacial asymmetry in
      malaysian infants with cleft lip and palate.
AB  - BACKGROUND: The application of three-dimensional computed tomography (3D CT) to
      analyse craniofacial morphology in individuals with cleft lip and palate (CLP)
      enables detailed assessments to be made of asymmetry in the region of the cleft
      and in regions distant from the cleft. The aim of this study was to compare
      craniofacial morphology in a sample of Malaysian infants with unoperated CLP with
      a control sample of unaffected Malaysian infants. METHODS: The study sample
      comprised 29 individuals: 10 with unilateral CLP (UCLP), 5 with bilateral CLP
      (BCLP), 7 with cleft lip and primary palate (CLPP), and 7 with isolated cleft
      palate (ICP). The control sample consisted of 12 non-cleft (NC) infants. All
      subjects were between 0.4 and 12.2 months of age. Nine mid-facial and 4 nasal
      bone landmarks were located on 3D CT scans and compared to a midline reference
      plane, which was created using the landmarks basion, sella, and nasion. Unpaired
      t tests and F tests were used to compare means and variances between sample
      groups, whereas paired t tests were used for comparisons within the UCLP and NC
      groups. RESULTS: Differences in variances of some mid-facial breadths and nasal
      bone dimensions were found in both male and female cleft groups when compared to
      the NC sample. In the UCLP group, some nasal bone and facial breadth dimensions
      were larger than in the NC sample and the nasal bone tended to deviate to the
      contralateral side of the cleft. CONCLUSION: CLP affects the size and orientation
      of the nasal bones and is associated with an altered morphology of some facial
      bones at positions distant from the region of the cleft.

PMID- 22135559
TI  - Risk Factors and Phenytoin Prophylaxis for Early Post-Traumatic Seizures among
      Patients with Traumatic Brain Injury.
AB  - BACKGROUND: Post-traumatic seizure is a well-known and serious complication of
      traumatic brain injury (TBI). The incidence and risk factors vary among study
      populations. Very little data have been published concerning this in the
      Malaysian population. The aim of this study was to ascertain the risk factors for
      the development of early post-traumatic seizures among patients with TBI.
      METHODS: This was a prospective observational study, carried out in Hospital
      Universiti Sains Malaysia, Kubang Kerian, Kelantan, under the Department of
      Neurosciences. A total of 157 patients, from all age groups, who were diagnosed
      with TBI were enrolled from June 2007 to December 2007. They were followed-up for
      12 months until death or their first post-traumatic seizure. Survival analysis
      with Kaplan-Meier curves and Cox proportional hazards regression was performed.
      RESULTS: A total of 11 (7.0%) of the patients developed early post-traumatic
      seizures. The risk factors for early post-traumatic seizures were young age (P =
      0.021, 95% CI 0.806 to 0.982) and intubated patients (P = 0.029, 95% CI 1.194 to
      25.913). The incidence of early post-traumatic seizures in the local population
      was 7.0%. CONCLUSION: The incidence of early post-traumatic seizures in the local
      population of Kelantan and Terengganu is comparable to the incidences reported
      elsewhere. Younger as well as intubated patients were at a higher risk of
      developing this condition. It may be necessary to give antiepileptic prophylaxis
      because any seizure could adversely affect morbidity and mortality. However, the
      study showed that antiepileptic drug was not beneficial in preventing late post
      traumatic seizures, but may have a role in preventing early seizures.

PMID- 22135560
TI  - Mastoid abscess in acute and chronic otitis media.
AB  - BACKGROUND: Mastoid abscess remains a recognised complication of otitis media
      despite the advent of antibiotics. The objectives of this study were to describe
      the risk factors in patients with mastoid abscess following acute and chronic
      otitis media and discuss the management of this infection. METHOD: A
      retrospective analysis was done on all patients who underwent mastoidectomy for
      mastoid abscess from January 2002 to December 2007. Data on the patients'
      presentation, associated complications, management, and follow-up were analysed.
      RESULTS: A total of 12 patients were enrolled in this study population. Group A
      consisted of patients with mastoid abscess preceded by acute otitis media, while
      Group B consisted of patients with mastoid abscess and chronic otitis media. In
      Group A (n = 7), 4 patients had a pre-morbid immunocompromised condition, but
      they did not have cholesteatoma. None of the patients in Group B (n = 5) had any
      pre-morbid illnesses. Out of 12 patients, 7 patients had associated extracranial
      complications, and 1 patient had intracranial complications. Most patients
      recovered well after mastoidectomy. Recurrence was noted in 1 patient who had
      acute lymphoblastic leukaemia. CONCLUSION: Mastoid abscess is still a recognised
      complication of acute otitis media, especially in patients who are
      immunocompromised. Immunocompetent patients may also develop mastoid abscess
      following chronic otitis media associated with cholesteatoma. Thus, early
      treatment of otitis media and close vigilant follow-up are advocated to ensure
      prompt detection of mastoid abscess complications.

PMID- 22135561
TI  - Computed tomography perfusion imaging on traumatic cerebral contusion: a
      preliminary report.
AB  - BACKGROUND: Brain ischaemia and infarction are the leading factors in morbidity
      and mortality of traumatic brain injury. This study aimed to determine the
      perfusion status of pericontusional hypodense areas in traumatic cerebral
      contusion METHODS: Ten patients involved in motor vehicle accidents were enrolled
      in this study, and contusions were diagnosed from plain computed tomography scans
      of the brain. Subsequent computed tomography perfusion (CTP) was performed to
      analyse the perfusion of pericontusional hypodense areas, which were divided into
      4 regions of interest (ROI). RESULTS: Most ischaemic perfusion was found in ROI 6
      (affecting 60% of patients), although the mean of the perfusion parameters were
      normal. A significant positive correlation was found between the perfusion status
      in the pericontusional area nearest to the skull vault (ROI 3) and its
      distance/thickness to the skull vault (r = 0.698, P = 0.025). Two adjacent
      pericontusional hypodense areas (ROI 4 and ROI 5) showed a significant positive
      correlation with each other (r = 0.667, P = 0.035) in terms of perfusion status.
      The presence of a hypodense pericontusional area is suggestive of oedema and
      perfusion disturbances. CONCLUSION: CTP is a useful, fast, and appropriate method
      in evaluating perfusion of pericontusional hypodensity area that may help the
      treating physician to provide an appropriate treatment to the patient.

PMID- 22135562
TI  - Chronic Sclerosing Sialadenitis (Kuttner's tumour) of the Parotid Gland.
AB  - Chronic sclerosing sialadenitis is a chronic inflammatory salivary gland disease.
      Kuttner reported 4 cases of submandibular gland lesions for the first time in
      1896. Chronic sclerosing sialadenitis is a very rare inflammatory lesion of the
      parotid gland and cannot be easily distinguished from salivary malignant masses.
      We reported a 28-year-old male with a painful parotid tumour, which grew slowly
      for 4 years.

PMID- 22135563
TI  - Perineal myxoid liposarcomas: a case report and literature review.
AB  - Myxoid liposarcoma is the major subtype of liposarcoma and commonly presents in
      the extremities, particularly in the thigh. We introduce an unusual case of a
      myxoid liposarcoma presenting as a large perineal swelling occupying the para
      rectal and para-anal spaces in a 49-year-old male patient. The diagnosis,
      management, and prognosis of myxoid liposarcoma are discussed. A literature
      review is performed for myxoid liposarcoma.

PMID- 22135564
TI  - Fatal airbag-mediated atlanto-occipital dislocation in a child.
AB  - An atlanto-occipital dislocation is a rare airbag-induced injury in trauma
      patients. We report a case of an atlanto-occipital dislocation in a 6-year-old
      patient who was an unrestrained passenger in the front seat of a vehicle involved
      in a low-speed motor vehicle accident. This case illustrates the fatal threat of
      airbag deployment to the child passenger travelling in the vehicle front seat
      even in a low-speed collision, and supports the recommendation that children
      under 12 years of age travelling in vehicles with dual airbag systems should be
      seated in the back.

PMID- 22135565
TI  - Multiple metastatic deposits in the head and neck region from a renal cell
      carcinoma.
AB  - Metastatic renal cell carcinoma (RCC) presenting with multiple deposits in the
      head and neck region is unusual. It is not uncommon for a RCC to metastasise to a
      distant site after years of a tumour-free period, but most of it would be
      expected to have a single site of deposit. We report a rare case of a patient who
      had a nephrectomy 10 years earlier for RCC and presented with tumours in the
      frontal sinus and posterior pharyngeal wall. Radiological imaging and histology
      confirmed metastatic RCC at both sites.

PMID- 22135566
TI  - MJMS at the Dawn of Its Electronic Era.
AB  - This special editorial assessed the recent developments in Malaysian Journal of
      Medical Sciences (MJMS) and examined the characteristics of the submission, peer
      review, and publication processes for MJMS. This retrospective analysis used
      information about the manuscripts submitted to MJMS during the one-year period
      (from 1 June 2010 to 31 May 2010) since the start of current online submission
      and review system (ScholarOne(TM) Manuscripts, Thomson Reuters). In addition, we
      also discussed the future directions of MJMS. Finally, we would like to recommend
      an annual internal audit for MJMS, which is very useful to monitor the growth of
      this journal progressively.

PMID- 22135567
TI  - Neuroimaging in the field of psychoses.
AB  - This review looks at the recent findings in the neuroimaging of the psychoses,
      with a view to clarifying the question of the unitary versus the two-disorder
      theory of psychosis. Schizophrenia is associated with significantly more cortical
      grey matter loss than bipolar disorder. The distribution of these losses is
      different; schizophrenia is characteristically associated with loss of the medial
      and middle frontal, the superior temporal gyri, and the dorsolateral prefrontal
      cortex, while bipolar disorder has particular loss in the medial frontal gyrus
      and the anterior cingulate cortex. Both disorders were associated with extensive
      white matter deficits. In summary, neuroimaging indicates different patterns of
      grey matter loss for schizophrenia and bipolar disorder. However, neuroimaging of
      white matter reveals a good deal of overlap between these two disorders. Thus,
      neuroimaging does not suggest a unitary psychosis or a two-psychosis model,
      instead it suggests a two-dimensional psychosis field, on which disorders are
      located according to two dimensions, the degree of grey matter loss and the
      degree of white matter abnormality.

PMID- 22135568
TI  - Modelling of Cerebral Tuberculosis: Hope for Continuous Research in Solving the
      Enigma of the Bottom Billion's Disease.
AB  - Cerebral tuberculosis is a severe type of extrapulmonary disease that is highly
      predominant in children. It is thought that meningeal tuberculosis, the most
      common form of cerebral tuberculosis, begins with respiratory infection followed
      by early haematogenous dissemination to extrapulmonary sites involving the brain.
      Host genetic susceptibility factors and specific mycobacteria substrains could be
      involved in the development of this serious form of tuberculosis. In this
      editorial the different animal models of cerebral tuberculosis are commented,
      highlighting a recently described murine model in which BALB/c mice were infected
      by the intratracheal route with clinical isolates, which exhibited rapid
      dissemination and brain infection. These strains were isolated from the
      cerebrospinal fluid of patients with meningeal tuberculosis; they showed specific
      genotype and induced a peculiar immune response in the infected brain. This model
      could be a useful tool to study host and bacilli factors involved in the
      pathogenesis of the most severe form of tuberculosis.

PMID- 22135569
TI  - Psychiatric intervention improved pregnancy rates in infertile couples.
AB  - BACKGROUND: Infertility has mental, social, and reproductive consequences. The
      aim of this study is to evaluate the effect of psychiatric intervention on the
      pregnancy rate of infertile couples. METHODS: In an experimental and intervention
      control study, 638 infertile patients who were referred to a university
      infertility clinic were evaluated; 140 couples (280 patients) with depression
      (from mild to severe) in at least one of the spouses were followed. All couples
      provided informed consent and were randomly numbered from 1 to 140. Those with
      even numbers were assigned to the psychological intervention before infertility
      treatment, and those with odd numbers were assigned to the psychological
      intervention during infertility treatment. Patients in the experimental group
      received 6-8 sessions of psychotherapy (individually) before beginning
      infertility treatment and were given Fluoxetine (antidepressant) at 20-60 mg per
      day during the psychotherapy period. The control group did not receive any
      intervention. Three questionnaires, the Beck Depression Inventory (BDI), the
      Stress Scale (Holmes-Rahe), and a sociodemographic questionnaire, were
      administered to all patients before and after treatment. The clinical pregnancy
      rate was compared between the two groups based on sonographic detection of
      gestational sac 6 weeks after the last menstrual period. The data were analysed
      by t test, X(2) and logistic regression methods. RESULTS: Pregnancy occurred in
      33 (47.1%) couples in the treatment group and in only 5 (7.1%) couples in the
      control group. There was a significant difference in pregnancy rate between the
      treatment and control groups (X(2)= 28.318, P < 0.001). To determine the
      effectiveness of psychiatric interventions on pregnancy, a logistic regression
      analysis was used. In this analysis, all demographic and infertility variables
      were entered in a stepwise manner. The results showed that in the treatment
      group, Pregnancy in the treatment group was 14 times higher than the control
      group (95% CI 4.8 to 41.7). Furthermore, cause of infertility was an effective
      factor of pregnancy. The adjusted odds ratio in male factor infertility was 0.115
      (95% CI 0.02 to 0.55) and in both factors (male and female) infertility was 0.142
      (95% CI 0.03 to 0.76) compared with the unexplained group. In this study, no
      other variables had any significant effect on pregnancy. CONCLUSION: Based on the
      effectiveness of psychiatric interventions in increasing pregnancy rate, it is
      crucial to mandate psychiatric counselling in all fertility centres in order to
      diagnose and treat infertile patients with psychiatric disorders.

PMID- 22135570
TI  - A prediction equation to estimate the maximum oxygen uptake of school-age girls
      from kolkata, India.
AB  - BACKGROUND: The 20-metre multistage shuttle run test is a useful method for the
      regular monitoring of aerobic fitness. However, the validity of the test should
      be established in the particular population prior to application. The aim of the
      study was to validate the applicability of the 20-metre multistage shuttle run
      test in non-athlete, girls from Kolkata, India. METHODS: Thirty-six untrained
      girls from different schools in Kolkata (age range 14-16 years) were recruited
      for the study. Direct estimation of cardiorespiratory endurance (VO(2)max)
      comprised treadmill exercise followed by expired gas analysis using Scholander
      micro-gas analyser. VO(2)max was indirectly predicted by the 20-metre multistage
      shuttle run test. RESULTS: The difference between the mean (SD) VO(2)max values
      of the direct measurement, 32.91 (2.66) ml.kg(-1).min(-1), and the 20-metre
      multistage shuttle run test, 33.79 (2.56) ml.kg(-1).min(-1), was statistically
      significant (P < 0.01). However, limits of agreement analysis suggested that the
      20-metre multistage shuttle run test can be applied for use with the studied
      population. Intra-class correlation coefficients also suggested good reliability
      of the 20-metre multistage shuttle run data. CONCLUSION: The results suggest that
      the use of the 20-metre multistage shuttle run test for the prediction of
      VO(2)max is justified in the studied population. For better prediction of
      VO(2)max, a new equation has been developed based on the present data for
      untrained girls from Kolkata.

PMID- 22135571
TI  - A randomised control trial on the use of topical methicillin in reducing post
      operative ventriculoperitoneal shunt infection.
AB  - BACKGROUND: A double-blind randomised control study was conducted on all patients
      who were admitted or referred to the Department of Neurosurgery, Sultanah Aminah
      Hospital, Johor Bahru, with a diagnosis of hydrocephalus where a
      ventriculoperitoneal shunt was indicated. METHODS: The period of study was from
      November 2005 to May 2007, and the follow-up period was 3 months after surgery.
      Randomisation was carried out in the operating room prior to the procedure. The
      scrub nurse selected a sealed envelope, which contained the assignment of each
      patient to 1 of 2 treatment groups: Group 1 patients were treated with topical
      methicillin, and Group 2 patients were not treated with topical methicillin.
      Prophylactic antibiotic, cefuroxime (25 mg/kg) was given intravenously at
      induction. Standard sterile operative technique was followed in preparing and
      draping the patients. RESULTS: A total of 90 patients were recruited in the
      study, and 13 (14.4%) patients developed an infection within 3 months post
      operation. Group 1 had a 8.9% risk of infection, and Group 2 had a 20% risk;
      however, there was no statistically significant post-operative
      ventriculoperitoneal shunt (VPS) infection reduction with the use of topical
      methicillin in VPS surgery (P = 0.230). Multivariate analysis showed that only
      duration of surgery had a significant influence on the incidence of post
      operative VPS infection in the non-methicillin group (P = 0.02). The non
      methicillin group had an 8 times greater risk of developing post-operative VPS
      infection than the methicillin group if surgery lasted longer than 1 hour.
      CONCLUSION: Topical methicillin had no significance in the reduction of post
      operative VPS infection.

PMID- 22135572
TI  - Peripheral Blood Lymphocyte Subset Counts in Pre-menopausal Women with Iron
      Deficiency Anaemia.
AB  - BACKGROUND: Iron-deficiency anaemia (IDA) is a major worldwide public health
      problem. Children and women of reproductive age are especially vulnerable to IDA,
      and it has been reported that these patients are more prone to infection. This
      study was done to evaluate alteration of lymphocyte subgroups in IDA. METHODS: In
      this prospective study, we investigated lymphocyte subsets in pre-menopausal
      women with iron-deficiency anaemia; 50 normal subjects and 50 IDA (hypochromic
      microcytic) cases were enrolled. Experimental and control anticoagulated blood
      samples were evaluated using flow cytometry to determine the absolute and
      relative numbers of various lymphocyte subgroups. Finally, the results of the
      patient and control groups were compared. RESULTS: Mean (SD) absolute counts of
      lymphocytes, CD3+ cells, CD3+/CD4+ subsets (T helper) and CD3+/CD8+ subsets (T
      cytotoxic) in the patient group were 2.08 (0.65) x 109/L, 1.53 (0.53) x 10(9)/L,
      0.87 (0.28) x 109/L, and 0.51 (0.24) x 10(9)/L, respectively. The results showed
      significant differences between case and control groups in mean absolute counts
      of lymphocytes (P = 0.014), T lymphocytes (P = 0.009), helper T cells (P =
      0.004), and cytotoxic T cells (P = 0.043). CONCLUSION: This study showed that
      absolute counts of peripheral blood T lymphocytes as a marker of cell-mediated
      immunity may be decreased in pre-menopausal women with iron-deficiency anaemia,
      and that these patients may be more prone to infection.

PMID- 22135573
TI  - Thirteen Years' Experience of Diaphragmatic Injury in Children from the Post
      Graduate Institute of Medical Sciences (PGIMS), Rohtak, India.
AB  - BACKGROUND: Diaphragmatic hernia is migration of abdominal viscera into the
      thoracic cavity through a defect in the diaphragm. In children, it is mostly
      congenital; traumatic diaphragmatic hernia being less common. This study aimed to
      review our experience with traumatic diaphragmatic rupture (TDR) and to identify
      the clinical findings and diagnostic modality that may help in early diagnosis
      and prompt therapy. METHODS: The study involved 11 children (1-18 years old) with
      TDR who were hospitalised between 1993 and 2005. In addition to clinical
      examination, a plain X-ray of the chest and abdomen, an ultrasound, barium
      studies, and a computerised tomography (CT) scan were used to evaluate the
      patients. RESULTS: All of the diaphragmatic ruptures occurred on the left side,
      with 10 occurring in the posterolateral part and 1 near the oesophageal hiatus.
      Two of our patients presented 7 and 10 days after the injury, and 1 patient
      presented 1 year after the trauma. CONCLUSION: TDR should remain a diagnostic
      possibility in children. These patients are best assessed using a CT scan. New
      research on stem cells and tissue-engineered bioprosthetics may pave the path for
      better future therapies in these cases.

PMID- 22135574
TI  - Factors affecting the outcomes in children post-myelomeningocoele repair in
      northeastern peninsular malaysia.
AB  - BACKGROUND: The present study aimed to evaluate the impact of multiple factors
      and outcomes (ambulatory function and sphincter function) on children with
      myelomeningocoele (MMC) following surgical repair. METHOD: A retrospective chart
      review of children that underwent surgery for MMC in the Hospital Universiti
      Sains Malaysia from 1 January 1990 to 31 December 2004 was conducted. Only those
      children who were followed-up for at least 18 months after the operation were
      included in the study. RESULTS: A total of 42 children with MMC were included in
      the study. Approximately 79% of the MMC were located in the lumbosacral and
      sacral regions. Thirty (71.4%) of the children had hydrocephalus, and 28 (67.7%)
      had a cerebrospinal fluid (CSF) shunt inserted. An analysis of the association
      between the predictors of ambulatory status revealed that hydrocephalus (P =
      0.013), the presence of a CSF shunt (P = 0.005), intact motor function at L3 and
      below (P < 0.001), and the presence of deep tendon reflexes (P < 0.001) were good
      factors of ambulatory status. Only 16.7% of the children did not have urinary or
      faecal incontinence. Hydrocephalus (P = 0.049) and low-level MMC (P = 0.028) were
      significantly associated with sphincter control. CONCLUSION: Multiple factors
      contributed to the outcomes in post-MMC repair children in terms of ambulation
      and sphincter function following a repair of MMC. The Spina Bifida Neurological
      Scale (SBNS) should be applied during the management of these children to
      identify neurological deterioration.

PMID- 22135575
TI  - Computed tomography of blunt spleen injury: a pictorial review.
AB  - The spleen is one of the organs most frequently injured in blunt abdominal
      trauma. Computed tomography (CT) scanning can accurately detect splenic injury
      and is currently the imaging modality of choice in assessing clinically stable
      patients with blunt abdominal trauma. The CT features of spleen injury include
      lacerations, subcapsular or parenchymal haematomas, active haemorrhage, and
      vascular injuries. We present a pictorial review of the spectrum of CT findings
      for blunt splenic injuries. This article will be a useful reference for
      radiologists and surgeons as CT scan is widely used for the assessment of splenic
      injuries and contributes to the current trend towards nonsurgical management of
      this injury.

PMID- 22135576
TI  - Unilateral axillary arch and variations in the axillary vein and intercostal
      nerves: a case report.
AB  - Knowledge of muscular, vascular, and neural variations in the axilla is of great
      clinical importance, especially in mastectomies, breast reconstruction, and
      axillary bypass operations. In the present paper, we report unilateral variations
      observed in the axillary region of a male cadaver. A fibromuscular axillary arch
      was observed on the right side. On the same side, there was a bifurcated axillary
      vein; a medial cutaneous nerve of the arm passed through and later ran beneath
      this axillary vein. In addition, the intercostobrachial nerve was absent on the
      right side. The clinical significance of the variations observed and their
      embryological basis are discussed in this paper.

PMID- 22135577
TI  - Metallic foreign body penetrating the carotid sheath: a case report.
AB  - Foreign bodies are a common problem seen in otolaryngological practice. Of the
      reported foreign bodies, metallic foreign bodies are a rare entity. One of the
      least common complications of foreign body ingestion is penetration and
      migration. We describe a case of a migrating metallic foreign body in a 50-year
      old woman with a history of accidental ingestion causing odynophagia. In the
      present case, the foreign body migrated extraluminally into the carotid sheath.
      Our review of literature revealed that few such cases have been reported.

PMID- 22135578
TI  - Acute Acalculous Cholecystitis after Laparoscopic Appendicectomy that Responded
      to Conservative Management.
AB  - Inflammation of the gallbladder without evidence of calculi is known as acute
      acalculous cholecystitis (AAC). AAC is frequently associated with a poor
      prognosis and a high mortality rate. Thus, early diagnosis and prompt surgical
      intervention has been recommended to improve the outcome of AAC. Herein, I
      present a case report of AAC complicating laparoscopic appendicectomy. Unlike
      previous studies that have reported the need for urgent intervention in patients
      with AAC, in this study, our patient responded to conservative management.
      Therefore, the management of AAC after laparoscopic appendicectomy should be
      individualised.

PMID- 22135579
TI  - Knee joint pain may be an indicator for a hip joint problem in children: a case
      report.
AB  - Knee joint pain is one of the most common complaints related to the skeletal
      system encountered by paediatricians. Knee joint pain generally occurs as the
      result of hypermobility and growing pains, though disorders manifesting as
      arthritis/arthralgia and orthopaedic problems should be considered in the
      differential diagnosis. A thorough and careful physical examination and
      laboratory and radiological findings are of importance for an accurate diagnosis.
      Although treatment should be based on the aetiology of the knee pain, non-steroid
      anti-inflammatory drugs can be used to alleviate the pain. A 7-year-old male
      patient presented with recurring pain in the left knee. Physical examination of
      the patient, laboratory tests, and radiological examination of the knee joint
      were normal; roentgenograms performed for a presumed hip joint problem revealed a
      focal cortical defect on the left femoral head and an increased effusion in the
      left hip joint space compared with the right counterpart. With this case report,
      we would like to highlight that paediatric health and diseases specialists
      (paediatricians) should consider hip joint pathologies when patients present with
      knee pain, particularly knee pain with an unidentified aetiology.

PMID- 22135580
TI  - For an international decade of the mind.
AB  - The International Decade of the Mind Project seeks to harness science across
      multiple disciplines to discover how human "mind" emerges from the biological
      activity of human brains. Given the complexity of the human brain, with
      approximately 10(11) neurons each with 10(4) connections, the effort will be
      daunting and require resources and expertise from many nations. The Decade of the
      Mind Project began as a United States initiative in 2007 and expanded to Europe
      in 2009 and then Asia in 2010. Here we advocate for a team-based approach to the
      Decade of the Mind initiative, where each nation contributes to the overall
      scientific effort with its own indigenous scientific expertise.

PMID- 22135581
TI  - Brain Activation during Addition and Subtraction Tasks In-Noise and In-Quiet.
AB  - BACKGROUND: In spite of extensive research conducted to study how human brain
      works, little is known about a special function of the brain that stores and
      manipulates information-the working memory-and how noise influences this special
      ability. In this study, Functional magnetic resonance imaging (fMRI) was used to
      investigate brain responses to arithmetic problems solved in noisy and quiet
      backgrounds. METHODS: Eighteen healthy young males performed simple arithmetic
      operations of addition and subtraction with in-quiet and in-noise backgrounds.
      The MATLAB-based Statistical Parametric Mapping (SPM8) was implemented on the
      fMRI datasets to generate and analyse the activated brain regions. RESULTS: Group
      results showed that addition and subtraction operations evoked extended
      activation in the left inferior parietal lobe, left precentral gyrus, left
      superior parietal lobe, left supramarginal gyrus, and left middle temporal gyrus.
      This supported the hypothesis that the human brain relatively activates its left
      hemisphere more compared with the right hemisphere when solving arithmetic
      problems. The insula, middle cingulate cortex, and middle frontal gyrus, however,
      showed more extended right hemispheric activation, potentially due to the
      involvement of attention, executive processes, and working memory. For addition
      operations, there was extensive left hemispheric activation in the superior
      temporal gyrus, inferior frontal gyrus, and thalamus. In contrast, subtraction
      tasks evoked a greater activation of similar brain structures in the right
      hemisphere. For both addition and subtraction operations, the total number of
      activated voxels was higher for in-noise than in-quiet conditions. CONCLUSION:
      These findings suggest that when arithmetic operations were delivered auditorily,
      the auditory, attention, and working memory functions were required to accomplish
      the executive processing of the mathematical calculation. The respective brain
      activation patterns appear to be modulated by the noisy background condition.

PMID- 22135583
TI  - Microbiology of lower respiratory tract infections in benin city, Nigeria.
AB  - BACKGROUND: Lower respiratory tract infections are among the most common
      infectious diseases of humans worldwide and continue to be a major cause of
      morbidity in Nigeria. This study focused on determining the microbial agents of
      lower respiratory tract infections, the effect of age and gender on its
      prevalence, and the susceptibility profile of bacterial isolates. METHODS: Sputum
      specimens were collected from 1539 patients with symptoms of lower respiratory
      tract infections. The sputum specimens were processed to recover microbial
      aetiologic agents and susceptibility profiles of bacterial isolates were
      determined using standard techniques. RESULTS: An overall prevalence of 18.91% of
      lower respiratory tract infections was observed in this study. There is no
      difference in the prevalence of lower respiratory tract infection between the
      genders (P = 0.649). The prevalence of lower respiratory tract infections
      increases significantly with age (P < 0.001), with patients 71 years and older
      having the highest prevalence. Klebsiella pneumoniae was the most predominant
      isolate causing lower respiratory tract infection while Acinetobacter species
      were the least predominant isolate. The fluoroquinolones, beta-lactams, and
      gentamicin showed moderate to high activity. CONCLUSION: Gender did not affect
      the prevalence, but age did. beta-lactams, fluoroquinolones, and gentamicin were
      the most active antibacterial agents and, therefore, the drugs of choice in
      treating lower respiratory tract infections in our setting.

PMID- 22135582
TI  - Ergonomic Training Reduces Musculoskeletal Disorders among Office Workers:
      Results from the 6-Month Follow-Up.
AB  - BACKGROUND: Musculoskeletal disorders are commonly reported among computer users.
      This study explored whether these disorders can be reduced by the provision of
      ergonomics education. METHODS: A cluster randomised controlled trial was
      conducted in which 3 units were randomised for intervention and received
      training, and 3 units were given a leaflet. The effect of intervention on
      workstation habits, musculoskeletal disorders, days and episodes of sick leave,
      and psychological well-being were assessed. RESULTS: A significant improvement in
      workstation habits was found, and the differences remained significant at the
      follow-up time point for keyboard, mouse, chair, and desk use. The largest
      reduction in the percentage of musculoskeletal disorders was in the neck region (
      42.2%, 95% CI -60.0 to -24.4). After adjusting for baseline values, significant
      differences were found at the follow-up time point in the neck, right shoulder,
      right and left upper limbs, lower back, and right and left lower limbs. No
      significant differences were found for the days and episodes of sick leave or the
      psychological well-being among workers after the intervention. CONCLUSION:
      Consistent reductions were observed for all musculoskeletal disorders at the
      follow-up time point, although the difference was not statistically significant
      for the upper back. The improvements in the musculoskeletal disorders did not
      translate into fewer days lost from work or improved psychological well-being.

PMID- 22135584
TI  - The Changes of Tear Status after Conventional and Wavefront-Guided IntraLASIK.
AB  - BACKGROUND: IntraLASIK is a LASIK surgery that involved IntraLase femtosecond
      laser for the corneal flap creating. The objective of this research was to
      investigate and compare the changes in tear status at 1 and 3 months after
      undergoing conventional IntraLASIK with Bausch & Lomb PlanoScan (PS) algorithm,
      Bausch & Lomb Zyoptix Tissue Saving (ZTS) algorithm, and wavefront-guided (WG)
      IntraLASIK with VISX CustomVue. METHODS: Tear status of 36 patients who were
      divided into 3 groups depending on the type of IntraLASIK they underwent (PS, n =
      13; ZTS, n = 9; WG, n = 14) was evaluated. Tear status was determined by
      classifying the category of the thickness of pre-corneal tear lipid layer, non
      invasive tear break-up time, and tear meniscus height. Repeated measures analysis
      of variance (ANOVA) and one way ANOVA were used for the statistical analyses.
      RESULTS: The category of the thickness of tear lipid layer, non-invasive tear
      break up time and tear meniscus height were neither significantly changed after
      IntraLASIK for all groups nor showed significant difference among groups at 1 and
      3 months post-IntraLASIK (P > 0.05). Blinking rate and palpebral aperture also
      had no significant changed after IntraLASIK. CONCLUSION: Both conventional (PS
      and ZTS) and WG IntraLASIK did not affect tear status up to 3 months post
      IntraLASIK. WG IntraLASIK did not show superiority in preserving tear status 1
      and 3 months post-surgery compared with conventional IntraLASIK.

PMID- 22135585
TI  - Influence of sitting and prone lying positions on proprioceptive knee assessment
      score in early knee osteoarthritis.
AB  - BACKGROUND: Knee proprioception is compromised in knee osteoarthritis. There are
      several ways of measuring proprioceptive acuity, but there is lack of consensus
      over the ideal testing position. The study aimed to evaluate the influence of 2
      testing positions (sitting versus prone lying) on proprioceptive knee assessment
      score in patients with early knee osteoarthritis. METHODS: The study included 70
      subjects who came to the Out-Patient Department with a diagnosis of early knee
      osteoarthritis. The subjects were assessed for their proprioceptive acuity scores
      in both the test positions at 30 degrees  and 60 degrees  of knee flexion using
      proprioceptive knee assessment device. They were asked to perform 5 trials in
      both testing positions with appropriate rest intervals. After initial assessment,
      the subjects were randomly allocated among group 1 and group 2. Treatment
      implementation was done for 8 weeks followed by re-evaluation: group 1 received
      context-specific proprioceptive retraining along with multijoint coupling
      strategies and group 2, conventional treatment. RESULTS: The subjects were
      compared using difference of pre- and post-treatment proprioceptive acuity
      scores. The difference of proprioceptive acuity impairment scores of the left
      knee at 30 degrees  and 60 degrees , and the right knee at 60 degrees  in prone
      lying position were statistically significant, with P value ranging from less
      than 0.001 to 0.028. CONCLUSION: It was found that the prone lying testing
      position was more sensitive than sitting position for assessing proprioceptive
      acuity for knee osteoarthritis.

PMID- 22135586
TI  - Chemical composition of gallstones from Al-jouf province of saudi arabia.
AB  - BACKGROUND: It is essential to understand the aetiopathogenesis of gallstone
      disease. This study was undertaken to determine the chemical composition of
      gallstones from patients living in Al-Jouf Province of Saudi Arabia. METHODS:
      This was a descriptive study where 46 gallstones from Al-Jouf Province of Saudi
      Arabia were analysed by semiquantitative titrimetric and colourimetric methods.
      The proportion of different types of gallstones was described using 95%
      confidence interval based on exact method. RESULTS: Gallstones were found more
      frequently in female patients (60.9%) than males (39.1%), and these stones were
      composed of pure cholesterol (54.3%), pure bilirubin (2.2%), or mixed stones
      (43.5%). The most common chemical constituent was cholesterol (82.6%), while
      bilirubin was seen in 26.1% of the stones. Calcium was present in 32.6% of the
      stones in the form of calcium salts of bilirubin and carbonate. Bilirubin
      containing stones were slightly more frequent in males than in females, while
      cholesterol-containing stones were less frequent in males. CONCLUSION: The
      findings indicate that gallstones in the Al-Jouf Province develop more frequently
      in the age group of the third decade of life, with more risk among females than
      males, and are predominated by cholesterol together with calcium bilirubinate and
      calcium carbonate.

PMID- 22135587
TI  - Robotic neurosurgery: a preliminary study using an active vision-guided robotic
      arm for bone drilling and endoscopic manoeuvres.
AB  - BACKGROUND: Surgical robots have been appearing in operating rooms over the past
      decade, and neurosurgery has been one of the pioneers in this area. In
      neurosurgery, the clinical use of robots has been limited to stereotactic
      procedures and endoscopic manoeuvres, although the brain is a unique organ and
      well-suited for robotic application. The aim of this study was to assess the
      ability of our vision-guided robotic system to perform basic neurosurgical
      procedures. METHODS: THE STUDY WAS DIVIDED INTO TWO PARTS: bone drilling and
      endoscopic manoeuvres. The robotic system was instructed to recognise targets on
      artificial skull models placed in different positions (supine, lateral, sitting,
      and prone) and to make burr holes. A total of 10 selected burr holes were used to
      assess the capability of the robot to insert an endoscope. RESULTS: The accuracy
      ranged 0.1-1.0 mm with repeatability ranged 0.03-0.92 mm. CONCLUSION: Generally,
      the present robotic system is able to perform the surgical tasks. However,
      further study is needed to refine the robotic system, including the safety
      mechanisms.

PMID- 22135588
TI  - A preliminary study on the prevalence of cardiovascular disease risk factors in
      selected rural communities in samarahan and kuching division, sarawak, malaysia.
AB  - BACKGROUND: It is important to understand the prevalence of risk factors for
      cardiovascular disease, especially in a rural setting. METHODS: A cross-sectional
      study was carried out in 238 rural households located in the Kuching and
      Samarahan divisions of Sarawak among individuals aged 16 years and above.
      Anthropometric measurements, blood levels of glucose and cholesterol, and blood
      pressure were collected. RESULTS: Prevalence of blood pressure in the
      hypertensive range was 43.1%. The highest rates of blood pressure in the
      hypertensive range were found in individuals aged above 60 years (38.6%) and 50
      59 years old (31.8%). Age was one factor found to be significantly associated
      with blood pressure in the hypertensive range (P < 0.001). Prevalence of obesity
      was 49.0%. The highest prevalence of obesity was found among those aged 40-49
      years (41.9%) and 50-59 years (29.9%). Gender was significantly associated with
      obesity (P = 0.004). The prevalence of blood cholesterol at risk was 21.6%, and
      the highest rate was found in the 40-49 years age group (34.0%). Fifty percent of
      respondents were found to have hyperglycaemia, with the highest prevalence in the
      50-59 years age group (37.5%). A significant association was found between
      obesity, blood pressure in the hypertensive range and blood glucose level. When
      compared with non-obese individuals, those who were obese were more likely to
      have blood pressure in the hypertensive range and hyperglycaemia. CONCLUSION: The
      risk of developing lifestyle-related diseases is no longer based on geographical
      or socio-economic factors.

PMID- 22135589
TI  - BCG Adenitis-Need for Increased Awareness.
AB  - Bacille Calmette-Guerin (BCG) vaccination for protection against tuberculosis has
      been in use for long. Although the vaccine is safe, its administration can result
      in complications such as BCG adenitis. We report here a series of children with
      BCG adenitis with a view to recognise and manage this condition. It is hoped that
      this case series would encourage the increased identification of this condition.

PMID- 22135590
TI  - The value of pre-operative embolisation in primary inferior vena cava
      paraganglioma.
AB  - We report a case of a 13-year-old boy who complained of progressive abdominal
      distension and symptoms of anaemia. Radiological investigations revealed that the
      child had a hypervascular tumour of the inferior vena cava (IVC). Unfortunately,
      the child presented with acute lower gastrointestinal bleed soon after the
      investigation. He underwent an urgent pre-operative embolisation, aimed to reduce
      the tumour vascularity. A total resection of the tumour, right nephrectomy, and
      partial duodenal resection were done within 24 hours post-embolisation. The child
      was stable postoperatively. The histopathological examination revealed
      chromogranin-positive paraganglioma originating from the IVC. We highlight the
      radiological findings of rare primary IVC paraganglioma and the role of
      embolisation prior to surgical removal of the tumour.

PMID- 22135591
TI  - Clavicle fracture and subclavian vessels disruption with massive haemothorax
      mimic intrathoracic injury.
AB  - We report a case of open fracture of the clavicle with subclavian artery and vein
      laceration and perforation of the parietal pleural below the first rib that
      caused massive haemothorax. Emergency thoracotomy and exploration followed by
      repair of both vessels were able to salvage the patient and the extremity.

PMID- 22135592
TI  - A rare case of a subcutaneous phaeomycotic cyst with a brief review of
      literature.
AB  - Phaeohyphomycosis consists of a heterogeneous group of fungal infections caused
      by more than 80 genera and species. Subcutaneous infection usually follows
      traumatic implantation of a fungus by a wooden splinter that the fungus inh abits
      as a saprophyte. The growth of the fungus forms verrucous plaques or a painless
      subcutaneous abscess. We report a subcutaneous cyst (phaeomycotic cyst) in the
      leg of a 60-year-old woman that developed after a thorn prick at that site. With
      the provisional diagnosis of an epidermoid cyst, she was treated with a simple
      excision of the cyst. However, histopathological examination of the cyst revealed
      the typical features of fungus, and a definitive diagnosis of a phaeomycotic cyst
      was made. As the infective aetiology was not considered clinically, the specimen
      was not sent for microbiological culture, and hence the exact species was not
      identified. As the lesion was localised, simple excision was sufficient
      treatment, and no recurrence was observed during 12 months of follow-up.

PMID- 22135593
TI  - Isolated ipsilateral nipple recurrence: important lessons to learn.
AB  - Most breast cancer recurrences occur in the surgical scars or within other
      quadrants of the same breast. Isolated tumour recurrence occurring in the nipple
      after breast-conserving surgery and radiotherapy is extremely unusual. The reason
      for this is unknown, but is speculated to be due to involved surgical margins or
      an occult involvement of the nipple-areolar complex in a breast cancer of the
      same breast. We present a case of a 44-year-old Indian woman who had recurrent
      tumour over her right nipple after an ipsilateral breast-conserving surgery that
      was followed by adjuvant chemotherapy and radiotherapy. There was no typical
      malignancy features from the mammogram. However, histopathological study
      confirmed a malignant growth that infiltrated into the dermis and the underneath
      breast tissue. Completion mastectomy was then performed and the patient was later
      treated with Taxane-based chemotherapy. Nipple recurrence after breast-conserving
      surgery and adjuvant radiotherapy may be confused with other nipple conditions
      such as Paget's disease of the breast. Comprehensive assessments, which include
      mammogram and biopsy, have proved that such recurrence do occur, as presented in
      this case. This warrants a specific management strategy.

PMID- 22135594
TI  - Malaysia collaborates with the new york academy of sciences to develop an
      innovation-based economy.
AB  - If Malaysia is to become a high-income country by 2020, it will have to transform
      into a knowledge-based, innovation economy. This goal will be achieved by
      developing an atmosphere conducive to experimentation and entrepreneurship at
      home; while reaching out to partners across the globe. One of Malaysia's newest
      partnerships is with the New York Academy of Sciences. The Academy has expertise
      in innovation and higher education and a long history of promoting science,
      education, and science-based solutions through a global network of scientists,
      industry-leaders, and policy-makers. Malaysia's Prime Minister, Dato' Sri Mohd
      Najib Tun Abdul Razak, leveraged the Academy's network to convene a science,
      technology, and innovation advisory council. This council would provide practical
      guidance to establish Malaysia as an innovation-based economy. Three initial
      focus areas, namely palm-oil biomass utilisation, establishment of smart
      communities, and capacity building in science and engineering, were established
      to meet short-term and long-term targets.

PMID- 22135595
TI  - Disorders of sex development: diagnostic approaches and management options-an
      islamic perspective.
AB  - Ambiguous genitalia, currently defined as disorders of sex development (DSD), are
      not uncommon in the Muslim community. DSD constitute a complex, major social and
      medical emergency, as several forms of congenital adrenal hyperplasia can lead to
      significant salt loss, which may lead to shock if unrecognised and not
      appropriately treated. To ensure that the affected individual has a high quality
      of life (a successful outcome), medical practitioners must quickly and correctly
      assign the individual's gender and effectively assuage the family's concerns and
      anxieties. It is important to review and understand the embryology and physiology
      of sexual differentiation, and to understand the various aetiological causes of
      sexual ambiguity. In this review, the diagnostic approach and management of
      ambiguous genitalia is thoroughly discussed from an Islamic point of view.

PMID- 22135596
TI  - In silico identification of drug targets for antifertility from natural products
      by differential reaction content analysis of metabolic pathways.
AB  - BACKGROUND: One of the major concerns of governments of developing and developed
      countries is to have a check on their population increase. Realising the
      importance of avoiding the harmful effects of synthetic compounds, scientists and
      researchers throughout the world are cooperating in efforts to design new and
      effective contraceptives from compounds of plant origin. METHODS: In this paper,
      we compared 11 plant species by analysing compounds showing antifertility
      properties with respect to the metabolic pathways involved. The Kyoto
      Encyclopedia of Genes and Genome pathway database was the source of metabolic
      pathway information. Protein sequences and classification numbers of unique
      enzymes exclusively present in certain species were identified using the Expert
      Protein Analysis System. RESULTS: Two enzymes, namely, L-aspartate dehydrogenase
      (EC no. 1.4.1.21) and trans-hexaprenyltranstransferase (EC no. 2.5.1.30), were
      identified as novel drug targets from the metabolic pathway analysis. Validation
      of the essential proteins identified through metabolic pathway comparison was
      done based on the literature information. CONCLUSION: The in silico analysis
      resulted in identification of 2 enzymes that are predicted to be the targets for
      putative antifertility drug. These enzymes can further be modelled to obtain
      their 3-dimensional structures with the help of various protein structure
      modelling softwares.

PMID- 22135597
TI  - Spasmogenic Activity of the Seed of Terminalia chebula Retz in Rat Small
      Intestine: In Vivo and In Vitro Studies.
AB  - BACKGROUND: Terminalia chebula Retz is traditionally used to relieve
      constipation. The current study was performed to investigate the pharmacological
      action of aqueous extract of Terminalia chebula seeds (ATC) in vitro and in vivo.
      METHODS: Terminal pieces of rat ileum were suspended in organ bath containing
      Tyrode solution. The ileum spontaneous motility frequency and contractility were
      recorded isotonically. To induce ileal contraction, carbachol and ATC were added
      to the organ bath. In addition, the effect of hexamethonium, indomethacin,
      atropine, and verapamil on the ATC-induced ileal contractions was also
      investigated. The effectiveness of ATC on relieving morphine-induced constipation
      was investigated in an in vivo study by measuring the faecal number, faecal water
      content, and intestinal transit ratio. RESULTS: ATC increased the frequency of
      ileum motility and tension of contraction dose-dependently (P < 0.05). Responses
      induced by ATC were inhibited by pre-treatment of the tissue with verapamil. The
      ATC activities were not affected by atropine, hexamethonium, and indomethacin.
      The faecal number and faecal water content were increased dose-dependently by ATC
      (P < 0.05). CONCLUSION: The excitatory effects of ATC on ileal contractile
      frequency and tension are possibly mediated through Ca(2+) channels activation.
      The results of the present study support the traditional usage of ATC for the
      treatment of constipation.

PMID- 22135598
TI  - Identification of Major and Minor Allergens of Black Tiger Prawn (Penaeus
      monodon) and King Prawn (Penaeus latisulcatus).
AB  - BACKGROUND: Prawns and shrimp are a frequent cause of seafood allergy mediated by
      IgE antibodies. Penaeus monodon and Penaeus latisulcatus, commonly known as black
      tiger prawn and king prawn, respectively, are among the most frequently consumed
      prawns in Malaysia. The aim of this study was to identify the IgE-binding
      proteins of these 2 prawn species. METHODS: Raw and boiled prawn extracts were
      prepared and then resolved by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE). IgE-immunoblotting was then performed using sera from
      patients with positive skin prick tests to the raw prawn extracts. RESULTS: SDS
      PAGE analysis of the raw extracts of both prawn species revealed 23 protein
      bands; the boiled extracts yielded fewer protein bands. The bands in the range of
      40 to 100 kDa were sensitive to heat and therefore were not found in the boiled
      extracts. Immunoblot of raw extracts of black tiger prawns and king prawns
      yielded 14 and 11 IgE-binding proteins, respectively, with molecular weights of
      between 15 and 200 kDa. Proteins at 36, 42, and 49 kDa were detected as the major
      allergens in both species of prawns. A protein of 75 kDa was also identified as a
      major allergen in black tiger prawns. Other potential allergens were also
      observed at various molecular masses. CONCLUSION: Proteins of 36, 42, and 49 kDa
      were identified as the major allergens of both species of prawns. The 36 and 42
      kDa proteins are hypothesised to be tropomyosin and arginine kinase,
      respectively. A high molecular weight protein of 75 kDa was found to be an
      additional major allergen in black tiger prawns.

PMID- 22135599
TI  - The Relationship between Media Use and Body Mass Index among Secondary Students
      in Kuching South City, Sarawak, Malaysia.
AB  - BACKGROUND: Overweight and obesity rates among adolescents have increased
      substantially over the years. This study aimed to determine the body mass index
      (BMI) of students and parents and the relationship among media use, BMI, socio
      demographic profiles, and snacking behaviour during television watching of
      secondary school students in Kuching South City. METHODS: In accordance with the
      two-stage sampling method, a total of 316 adolescents aged 13-17 years from 7
      secondary schools participated. Data were collected using questionnaire and
      anthropometric measurement. Independent t test, one-way ANOVA, Mann-Whitney U
      test, and chi-square test were performed. RESULTS: The mean BMI was 20.56 kg/m(2)
      (SD 4.33) for boys and 20.15 kg/m(2) (SD 3.91) for girls. No significant
      difference in terms of z score for BMI-for-age or socio-demographic factors was
      found. The mean duration of time devoted to media use was 4.69 hours (SD 2.93) on
      weekdays and 5.69 hours (SD 2.87) on weekends. Boys were found to spend more
      hours on media use than did the girls (t = 4.293, P < 0.01). Respondents were
      reported to consume more cereal compared with soft drinks and junk foods.
      Respondents whose fathers worked in the private sector devoted the fewest hours
      to media use, whereas those with self-employed fathers devoted the most time to
      media use. Respondents with mothers who were employed spent more time on media
      use than did respondents whose mothers were housewives (F = 4.067, P < 0.01). No
      significant difference was found between BMI and media time or snacking habits.
      CONCLUSION: This finding indicated that media time has no effect on body weight,
      because respondents were found to have normal weight and to consume less
      unhealthy food.

PMID- 22135600
TI  - A comparison study of conjunctiva disorders in technical and administrative
      sawmill workers in Nigeria.
AB  - BACKGROUND: Workers in the sawmilling industry are at risk of various ocular
      hazards as a direct result of the sawmilling processes. The aim of this study was
      to determine the pattern of conjunctival disorders between technical and
      administrative sawmill workers in Benin, Nigeria. METHODS: A cross-sectional
      study was performed on sawmill workers in Benin, Nigeria, between January and May
      2009, with the aid of pre-tested questionnaires. Ocular examination was performed
      on all subjects. Data obtained were recorded and analysed using SPSS version 13.
      RESULTS: A total of 553 sawmill workers were studied, among whom 449 (81.2%) and
      104 (18.8%) were technical and administrative workers, respectively. There were
      496 (89.7%) males and 57 (10.3%) females. The age range was 15-80 years, with a
      mean of 38.9 years (SD 12.8). Pingueculum was found in 127 (23%) workers, among
      whom 122 (27.2%) were technical workers and 5 (4.8%) were administrative workers.
      Pterygium was present in 65 (11.8%) workers, among whom 64 (14.3%) were technical
      workers and 1 (1%) was an administrative worker. Seven (1.6%) technical workers
      used protective eyewear; 2 (0.4%) wore this protective eyewear regularly.
      CONCLUSION: Technical sawmill workers are at risk of developing conjunctival
      disorders, which result from chronic ocular irritation. This can be prevented by
      the provision of protective eye devices in the workplace.

PMID- 22135601
TI  - The Socio-Demographic and Clinical Factors Associated with Quality of Life among
      Patients with Haematological Cancer in a Large Government Hospital in Malaysia.
AB  - BACKGROUND: The paper examined the quality of life of haematological cancer
      patients according to their socio-demographic profiles and clinical diagnoses.
      METHODS: This cross-sectional study was conducted at the tertiary referral centre
      of Ampang Hospital, Kuala Lumpur, involving 105 patients. The European
      Organisation for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30)
      questionnaire was used to measure their quality of life. RESULTS: The study
      involved patients diagnosed with all types of haematological cancer, including
      non-Hodgkin lymphoma (NHL), acute myelogenous leukaemia (AML), acute
      lymphoblastic leukaemia (ALL), Hodgkin lymphoma (HL), and multiple myeloma (MM),
      with a response rate of 83.3%. The patients with ALL, HL, without NHL, and
      without MM were younger than other patients. There were significant differences
      in quality of life scores in different socio-demographic groups and types of
      cancer diagnosis. The global quality of life of the female patients was much
      better than that of the male patients. Patients who were 40 years old or younger
      had a better global quality of life and physical functioning, as well as fewer
      symptoms of constipation, nausea, and vomiting. Employed patients were in less
      pain but showed greater impairments of cognitive function than did unemployed
      patients. Patients who earned a monthly wage of RM1000 or less had reduced
      physical function, more symptoms of pain, and more financial difficulties
      compared with patients who earned more. Patients with AML tended to have better
      physical functioning than did patients with MM, whose physical functioning was
      impaired. Comparatively, more symptoms of dyspnoea were found in ALL and HL
      patients than in other types of lymphoma. Compared with other patients, those
      with ALL had a greater loss of appetite, and other lymphoma patients had fewer
      symptoms of pain. Patients with NHL had impaired role functioning and more
      constipation compared with other patients. The results were all statistically
      significant (P < 0.05). CONCLUSION: The quality of life of haematological cancer
      patients is affected by socio-demographic factors and clinical diagnoses. Efforts
      should be made to improve the overall quality of life of these patients.

PMID- 22135602
TI  - Stress and coping strategies of students in a medical faculty in malaysia.
AB  - BACKGROUND: Stress may affect students' health and their academic performance.
      Coping strategies are specific efforts that individuals employ to manage stress.
      This study aimed to assess the perception of stress among medical students and
      their coping strategies. METHODS: A cross-sectional study was conducted among 376
      medical and medical sciences undergraduates in Management and Science University
      in Malaysia. Stress was assessed by a global rating of stress. Sources of stress
      were assessed using a 17-item questionnaire. The validated Brief COPE inventory
      was used to assess coping strategies. RESULTS: The majority of respondents were
      females (64.4%), aged 21 years or older (63.0%), and were Malays (68.9%). Forty
      six percent felt stress. The most common stressor was worries of the future
      (71.0%), followed by financial difficulties (68.6%). Significant predictors of
      stress were smoking (OR = 2.9, 95% CI 1.3-6.8, P = 0.009), worries of the future
      (OR = 2.1, 95% CI 1.3-3.4, P = 0.005), self-blame (OR = 1.3, 95% CI 1.1-1.5, P =
      0.001), lack of emotional support (OR = 0.8, 95% CI 0.7-0.9, P = 0.017), and lack
      of acceptance (OR = 0.8, 95% CI 0.6-0.9, P = 0.010). Students used active coping,
      religious coping reframing, planning, and acceptance to cope with stress.
      CONCLUSION: Stressors reported by the students were mainly financial and academic
      issues. Students adopted active coping strategies rather than avoidance. Students
      should receive consultation on how to manage and cope with stress.

PMID- 22135603
TI  - Towards the prevention and management of prostatic diseases in Nigeria: a
      framework.
AB  - The prevalence of prostatic diseases is reportedly high in Nigeria, and in some
      cases, it is comparable to figures from industrialised countries. However, to
      date, the research and policy responses in Nigeria are regrettably inadequate.
      The presence of "the double burden of diseases" and a limited appreciation of
      recent trends in prostatic diseases may be partly responsible for this situation.
      Given the frequently meagre healthcare budgetary allocations, it is pertinent to
      develop a properly thought-out plan for the prevention and management of
      prostatic diseases in Nigeria. A framework aimed at contributing to the
      development of such a plan is presented here. The development of a Central
      Prostatic Diseases Unit (CPDU) in the Federal Ministry of Health is advocated.
      The CPDU would be responsible for planning research and information dissemination
      programmes. Emphasis should be placed on targeting modifiable risk factors at the
      population level, proper surveillance to identify emerging trends, and research
      on both the operational dynamics and the efficacy of locally available herbs that
      could be useful in the management of prostatic diseases.

PMID- 22135604
TI  - Wernicke's Encephalopathy in a Patient with Nasopharyngeal Carcinoma: Magnetic
      Resonance Imaging Findings.
AB  - We report a case of Wernicke's encephalopathy in a patient with nasopharyngeal
      carcinoma with a 3-month history of poor oral intake related to nausea and
      vomiting due to chemotherapy. The patient later developed deep coma while
      receiving in-patient therapy. Magnetic resonance imaging of the brain revealed
      typical findings of Wernicke's encephalopathy. The patient was treated with
      thiamine injections, which resulted in subsequent partial recovery of
      neurological function. This paper stresses the importance of magnetic resonance
      imaging for prompt diagnosis of Wernicke's encephalopathy.

PMID- 22135605
TI  - A case of isolated laryngeal candidiasis mimicking laryngeal carcinoma in an
      immunocompetent individual.
AB  - Respiratory fungal infections are usually found in immunocompromised individuals
      who have received either long-term steroid therapy or broad-spectrum anti
      microbial therapy or have a non-resolving underlying chronic disease. These
      infections are seen as a part of bronchopulmonary fungal infections, and their
      isolated and primary occurrence as laryngeal diseases is highly uncommon.
      Laryngeal fungal infections can also mimic various diseases, such as
      gastroesophageal reflux disease, granulomatous diseases, leukoplakia, and
      carcinoma, thereby misleading the treating team from correct diagnosis and
      management. It is therefore important to identify the lesion at the earliest
      point possible to avoid morbid or life-threatening consequences. We report a case
      of isolated laryngeal candidiasis in an immunocompetent Indian male with an
      unusual presentation mimicking laryngeal carcinoma. The clinical and histological
      features are highlighted with a review of relevant literature to demonstrate the
      possibility of such an isolated fungal lesion, even in an immunocompetent
      individual.

PMID- 22135606
TI  - An unusual case of amoebic liver abscess presenting with hepatic encephalopathy:
      a case report.
AB  - Amoebic liver abscess (ALA) with jaundice and encephalopathy is a rare occurrence
      and has been recognised and studied more frequently in recent years. We present a
      case of massive ALA presenting with jaundice, hepatic encephalopathy, and
      septicaemia that was treated successfully with percutaneous drainage of the
      abscess, right-sided chest tube insertion, and anti-amoebic therapy.

PMID- 22135607
TI  - A case report of atypical teratoid/rhabdoid tumour in a 9-year-old girl.
AB  - Primary central nervous system atypical rhabdoid/teratoid tumour (ATRT) is a rare
      and highly malignant tumour that tends to occur in infancy and early childhood.
      The majority of tumours (approximately two-third) arise in the posterior fossa.
      The optimal treatment for ATRT remains unclear. Options of treatment include
      surgery, radiotherapy, and chemotherapy. Each of their role is still not clearly
      defined until now. The prognosis of the disease is generally unfavourable. This
      is a case report of ATRT in an atypical site in a 9-year-old girl.

PMID- 22135608
TI  - Subarachnoid hemorrhage associated with epidemic hemorrhagic fever: a rare case
      report.
AB  - Nervous system injuries associated with epidemic hemorrhagic fever (EHF) are not
      rarely seen. However, cerebrovascular disease arising from EHF is rarely reported
      in the literature. A 50-year-old male patient suffered from subarachnoid
      hemorrhage (SAH). No abnormal condition was found in intracranial vascular
      digital subtraction angiography (DSA). But, this patient presented with positive
      hantavirus-IgM and IgG, with typical clinical process, which lead to the
      diagnosis of EHF followed by SAH. To our knowledge, SAH associated with EHF has
      not been previously reported. A meticulous assessment of EHF patients with a
      serious condition had one or more central nervous system (CNS) abnormalities,
      such as sudden headache, vomiting, confusion, meningismus, and convulsions, which
      is necessary for diagnosing and giving timely treatment to improve the prognosis.

PMID- 22135609
TI  - Umbilical arterial blood gas and perinatal outcome in the second twin according
      to the planned mode of delivery.
AB  - PURPOSE: To compare umbilical arterial gas parameters in the second twin of twin
      pregnancies according to the mode of delivery. METHODS: We retrospectively
      analyzed the medical records of twin deliveries after 34 weeks of gestation for 3
      years. Excluding the cases which underwent emergency cesarean delivery during
      trial of labor, a total of 79 twin gestations had umbilical arterial blood gas
      values available and were and divided into cesarean delivery group (N=40) and
      vaginal delivery group (N=39). The mean differences of umbilical arterial blood
      parameters and the Apgar score between the first and second twin in each
      pregnancy were compared according the mode of delivery. RESULTS: The differences
      of umbilical arterial gas parameters between twin siblings showed no significant
      difference according to the mode of delivery. With regard to the 1 minute and 5
      minute Apgar scores, the differences between twin siblings are significantly
      increased in vaginal delivery group compared to cesarean delivery group (p=0.048,
      and p=0.038, respectively). In comparing the 28 cases delivered vaginally with an
      inter-twin delivery interval < 10 minutes and 40 cases delivered by cesarean
      section, no significant differences were observed in the umbilical arterial gas
      parameters and Apgar scores. CONCLUSION: The inter-twin umbilical arterial blood
      gas parameters according to the mode of delivery showed no difference. For twin
      deliveries, it is relatively safe to plan for a vaginal delivery, but an effort
      should be made to reduce the inter-twin delivery interval time.

PMID- 22135610
TI  - Oral piercing and oral diseases: a short time retrospective study.
AB  - Body piercing indicates the puncturing of a part of the body in which jewelry may
      be worn. In recent years, oral piercing is increasingly popular especially among
      young people. Body piercing has to be considered as a surgical procedure to all
      intents and purposes and, as such, has to be performed only by qualified
      personnel able to assure high standards of professionalism in facilities subject
      to sanitary inspections.The aim of the present work is to verify what risks
      patients may be exposed to and what complications may occur after a healthcare
      professional performs oral piercing.Our retrospective study includes 108 patients
      (74 males and 34 females) aged between 14 and 39 years, who had oral piercing
      done 12+/-4 months earlier. All the patients underwent clinical examination to
      reveal the possible presence of late complications. After piercing, none of the
      108 patients developed widespread complications.Although all patients said they
      had followed the piercers' instructions, 96% of them reported postoperative local
      complications such as bleeding within 12 hours of piercing (90%), perilesional
      edema for 3+/-2 days after piercing surgery (80%), and persistent mucosal atrophy
      (70%).

PMID- 22135611
TI  - Body weight reducing effect of oral boric acid intake.
AB  - BACKGROUND: Boric acid is widely used in biology, but its body weight reducing
      effect is not researched. METHODS: Twenty mice were divided into two equal
      groups. Control group mice drank standard tap water, but study group mice drank
      0.28mg/250ml boric acid added tap water over five days. Total body weight
      changes, major organ histopathology, blood biochemistry, urine and feces analyses
      were compared. RESULTS: Study group mice lost body weight mean 28.1% but in
      control group no weight loss and also weight gained mean 0.09% (p<0.001). Total
      drinking water and urine outputs were not statistically different. Cholesterol,
      LDL, AST, ALT, LDH, amylase and urobilinogen levels were statistically
      significantly high in the study group. Other variables were not statistically
      different. No histopathologic differences were detected in evaluations of all
      resected major organs. CONCLUSION: Low dose oral boric acid intake cause serious
      body weight reduction. Blood and urine analyses support high glucose, lipid and
      middle protein catabolisms, but the mechanism is unclear.

PMID- 22135612
TI  - Repercussions of surgically assisted maxillary expansion on nose width and
      position of septum and inferior nasal conchae.
AB  - The aim of the present study was to assess the clinical and radiographic
      repercussions of surgically assisted maxillary expansion on the septum, nasal
      cavity and nasal conchae. The sample was made up of 15 patients with skeletal
      maturity (9 females and 6 males between 16 and 45 years of age) and maxillary
      transverse deficiency. Assessments were performed through anterior rhinoscopy and
      frontal cephalometric radiographs on three occasions: (T0) preoperative period,
      (T1) locking of the expander and (T2) six months following the locking procedure.
      An increase was observed in the basal portion of the pyriform aperture and
      distances between the lateral wall of the basal portion of the pyriform aperture
      and the septum. The radiographic exam revealed that the nasal septum did not
      undergo any statistically significant change in its position. Moreover, no
      significant changes in the position of the nasal septum or nasal conchae were
      detected throughout the three evaluation times. The results suggest that
      surgically assisted maxillary expansion is capable of widening the basal portion
      of the pyriform aperture, with little repercussion on the anterior position of
      the nasal septum and inferior nasal conchae.

PMID- 22135613
TI  - Use of cone-beam computerized tomography for evaluation of bisphosphonate
      associated osteonecrosis of the jaws in an experimental rat model.
AB  - BACKGROUND: Bisphosphonate-induced osteonecrosis of the jaw (BONJ) is a
      frequently reported complication. The aim of this study was to investigate the
      clinical and histopathological presentation of BONJ with the Hounsfield score and
      to evaluate the reliability of the score for determining necrosis in an animal
      model. MATERIAL/METHODS: Eighty rats were prospectively and randomly divided into
      two groups of 40 each: a control group and an experimental group. Half of the
      animals from each group underwent extraction of the left mandibular molars, and
      the other half underwent extraction of the left maxillary molars under
      pentobarbital-induced general anesthesia. All animals were euthanized 28 days
      after tooth extraction. Maxillae and mandibles were extracted, cone beam computed
      tomography (CBCT) was performed, and Hounsfield scores were evaluated. RESULTS:
      The Hounsfield scores of the experimental group were found to be compatible with
      chronic osteomyelitis and periosteal reactions. The Hounsfield scores of the
      control group were compatible with a healthy healing period. CONCLUSION: In light
      of these results, both cone beam computed tomography (CBCT) and the Hounsfield
      Units (HU) evaluations together are thought to be efficient in the diagnosis of
      BONJ.

PMID- 22135614
TI  - Comparison of cervical parameters by three-dimensional ultrasound according to
      parity and previous delivery mode.
AB  - BACKGROUND: We would like to find out that whether the patient's parity, previous
      delivery mode and previous labor could influence cervical parameters. Cervical
      length, volume and width were measured using two-dimensional (2D) and three
      dimensional (3D) transvaginal ultrasound on normal pregnant women. METHOD: This
      study was conducted between January 2009 and December 2010 in singleton pregnant
      women who were admitted for routine antenatal care at hospitals in affiliation
      with the Catholic University, Seoul, Korea. The study group was classified by
      parity (nullipara and multipara) and previous delivery mode (cesarean section
      group and vaginal delivery group). The previous cesarean section group was
      divided by elective group who did not undergo labor and labor group who underwent
      labor. Cervical parameters such as cervical length, volume and width were
      measured using 2D and 3D ultrasound examinations in the first and second
      trimesters and the results were analyzed between those groups mentioned above.
      RESULTS: One hundred and twenty-one pregnant women in their 1st trimester and 233
      pregnant women in their 2nd trimester (a total of 354) were enrolled in this
      study. Cervical parameters were not statistically significant from parity, nor
      previous delivery mode and previous labor in 1st trimester. Cervical volumes were
      not statistically significant from nullipara and elective cesarean section groups
      (35.96+/-9.81 vs. 34.73+/-9.75 cm3), but the nullipara groups were significantly
      lowered in the vaginal group (35.96+/-9.81 vs. 43.10+/-11.87 cm3) in 2nd
      trimester. For the nullipara group, cervical widths were not statistically
      significant in the elective cesarean section group but these were significantly
      lower than labor and previous vaginal group in the 2nd trimester. CONCLUSION: The
      cervical volume and width have an influence on parity, previous delivery mode and
      labor in the 2nd trimester.

PMID- 22135616
TI  - The effect of irrigation temperature on bone healing.
AB  - OBJECTIVE: Osteotomies, performed by rotational instruments, can cause
      temperature rise on the bone and elevated temperature can disrupt the bone
      healing. When the osteotomies are performed for the insertion of miniscrews, the
      bone healing disruption may cause stability loosening or failures. Saline
      irrigation is mostly used for the prevention of the heat generation during
      osteotomy. PURPOSE: The purpose of this study was to evaluate the effect of the
      saline irrigation temperature on bone healing. MATERIAL AND METHOD: Standardized
      drilling and miniscrew placement was performed in the tibias of 18 Sprague Dawley
      rats with rotating bur uncooled, cooled with 25 degrees C and 4 degrees C saline
      irrigations. After the 21 days, the difference in healing was observed between
      the uncooled and cooled groups. RESULTS: Although there was no statistically
      significant difference between the group irrigated with 25 degrees C and 4
      degrees C saline for newly bone formation, osteoblasts were seen more active and
      bone marrow was more dynamic in group 4 degrees C than group 25 degrees C. There
      is no disadvantage to use 25 degrees C, but it may be better to use 4 degrees C
      for rapid healing.

PMID- 22135617
TI  - Large mass arising from the tongue as an initially and sole manifestation of
      Kaposi sarcoma.
AB  - We report a 30- year-old Iranian woman presenting with a red to yellowish, well
      demarcated, painless exophytic and lobulated mass originating from the right hand
      side of the tongue. An excisional biopsy was obtained and it was diagnosed
      histopathologically as Kaposi's sarcoma by detecting atypical spindle cells with
      rare mitoses delineating blood-filled vascular slits.

PMID- 22135618
TI  - Lateral ventricular meningioma presenting with intraventricular hemorrhage: a
      case report and literature review.
AB  - Lateral ventricular meningiomas presenting with primary intraventricular
      hemorrhage are extremely uncommon. We report here a case of primary
      intraventricular hemorrhage attributable to a lateral ventricular meningioma.
      This case concerns a 46-year-old female patient who presented with sudden onset
      of headache. Computed tomography (CT), computed tomography angiography (CTA) and
      magnetic resonance imaging (MRI) examinations showed hemorrhage from a ruptured
      tumor mass, which was pathologically confirmed as a transitional meningioma. The
      patient underwent surgical treatment and had a good prognosis. A retrospective
      review of eight previous cases of hemorrhage from ruptured lateral ventricular
      meningiomas revealed that hemorrhage of lateral ventricular meningiomas and
      hemorrhage of meningiomas at other intracranial sites have similar causes. The
      clinical and pathological features of ruptured lateral ventricular meningiomas
      are consistent with those of unruptured lateral ventricular meningiomas. As this
      clinical entity is extremely rare, attention is called for while performing
      differential diagnosis.

PMID- 22135620
TI  - Addiction treatment ultimatums and U.S. health reform: A case study.
AB  - AIMS: Increased access to health care, including addiction treatment, has long
      been a goal of health reform in the U.S. An unanswered question is whether reform
      will change the way people get to addiction treatment; when treatment is easily
      accessible, do individuals self-refer, or do they still enter treatment via
      ultimatums, and if so, from which sources? To begin examining this, we used a
      single case study of a U.S. health plan that provides access similar to that
      called for in health reform.  METHOD: Using a case study method of data from
      studies conducted in a large, private non-profit, integrated managed care health
      plan which includes addiction services, we examined the prevalence and source of
      ultimatums to enter treatment, and the characteristics of those receiving them.
      The plan is highly representative of changes to U.S. health care and other
      countries due to health reform.  RESULTS: Many individuals entering addiction
      treatment had received an ultimatum stemming from employment, legal, medical, and
      family sources. Having more employment problems, an occupation with public safety
      concerns, being older, male, and ethnicity predicted an employment ultimatum.
      Higher legal problem severity predicted a legal ultimatum. More men (and younger
      people) had family ultimatums, and more women (and older people) had medical
      ultimatums. Being younger, male, married, having higher employment and family
      problem severity, and being drug or combined drug/alcohol dependent rather than
      dependent on alcohol-only predicted an ultimatum from one's family. On the whole,
      an ultimatum from one source was not related to having one from another source.
      Those most likely to receive ultimatums from multiple sources were women, those
      separated/divorced, and those having higher psychiatric and legal problem
      severity.  CONCLUSIONS: Even in an insured population with good access to
      addiction treatment, individuals often receive ultimatums to enter treatment
      rather than being self-referred. Understanding the treatment entry process, and
      how it is affected by health care systems, could benefit from international and
      other comparative research.

PMID- 22135619
TI  - A paired-comparision of the Multifunction Cardiogram (MCG) and sestamibi SPECT
      myocardial perfusion imaging (MPI) to quantitative coronary angiography for the
      detection of relevant coronary artery obstruction (>=70%) - a single-center study
      of 116 consecutive patients referred for coronary angiography.
AB  - BACKGROUND: An analysis of the US National Cardiovascular Data Registry has
      revealed that only 38% of patients referred for coronary angiography after non
      invasive coronary testing have relevant coronary obstruction (CO) (>=70%) of one
      or more coronary arteries. METHODS: A single-center trial was undertaken in 165
      consecutive, symptomatic patients with either known or suspected coronary disease
      and/or valve disease(VHD) who agreed to undergo cardiac catheterization and
      coronary angiography if stress myocardial perfusion imaging was abnormal. A total
      of 116 patients with abnormal SPECT MPI tests, persistent chest pain, or
      significant VHD underwent final analysis. An MCG coronary obstruction (CO) score
      of >= 4.0 was considered indicative of relevant CO (>=70%) in one or more
      coronary arteries. Angiographic results were finalized by consensus of two
      angiographers. RESULTS: CO (>=70%) was present in 53 of 116 patients (46%). The
      MCG CO score was significantly higher for patients with relevant CO (5.4 +/- 1.9
      vs. 2.5 +/- 1.9). The MCG correctly classified 103 of the 116 patients (89%)
      enrolled in the study as either having or not having CO (>=70%) (sensitivity-
      91%; specificity- 87%; NPV- 92%; PPV- 86%). SPECT MPI was abnormal in 99 of the
      116 (85%) patients undergoing catheterization, but correctly classified only 54
      of the 116 patients (47%) entered in the study as either having or not having
      relevant CO (sensitivity-85%; specificity-14%; NPV - 53%; PPV- 45%). CONCLUSIONS:
      The MCG was shown in this paired-comparison trial with SPECT MPI to safely and
      accurately identify patients with relevant CO (>=70%) prior to catheterization.

PMID- 22135621
TI  - Diabetes mellitus: the long way of standardization of HbA(1c) to the level of
      highest metrological order.
AB  - Glycated haemoglobin (HbA(1c)) measurements are used in clinical studies and for
      the management of diabetic patients. Various efforts were made to standardize the
      HbA(1c) measurements with consensus standards and standards based on a reference
      measurement procedure with external calibration. According to ISO 17511 a
      standard should meet highest accuracy possible, have a defined uncertainty of
      measurement and the calibration should be traceable to SI units. For HbA(1c) this
      has been realized using a LC-ID-MS procedure based on the existing reference
      measurement procedure.

PMID- 22135622
TI  - New Clues to Breast Cancer Heterogeneity.

PMID- 22135615
TI  - Anorexia nervosa: a unified neurological perspective.
AB  - The roles of corticotrophin-releasing factor (CRF), opioid peptides, leptin and
      ghrelin in anorexia nervosa (AN) were discussed in this paper. CRF is the key
      mediator of the hypothalamo-pituitary-adrenal (HPA) axis and also acts at various
      other parts of the brain, such as the limbic system and the peripheral nervous
      system. CRF action is mediated through the CRF1 and CRF2 receptors, with both HPA
      axis-dependent and HPA axis-independent actions, where the latter shows nil
      involvement of the autonomic nervous system. CRF1 receptors mediate both the HPA
      axis-dependent and independent pathways through CRF, while the CRF2 receptors
      exclusively mediate the HPA axis-independent pathways through urocortin. Opioid
      peptides are involved in the adaptation and regulation of energy intake and
      utilization through reward-related behavior. Opioids play a role in the addictive
      component of AN, as described by the "auto-addiction opioids theory". Their
      interactions have demonstrated the psychological aspect of AN and have shown to
      prevent the functioning of the physiological homeostasis. Important opioids
      involved are beta-lipotropin, beta-endorphin and dynorphin, which interact with
      both u and kappa opioids receptors to regulate reward-mediated behavior and
      describe the higher incidence of AN seen in females. Moreover, ghrelin is known
      as the "hunger" hormone and helps stimulate growth hormone (GH) and hepatic
      insulin-like-growth-factor-1(IGF-1), maintaining anabolism and preserving a lean
      body mass. In AN, high levels of GH due to GH resistance along with low levels of
      IGF-1 are observed. Leptin plays a role in suppressing appetite through the
      inhibition of neuropeptide Y gene. Moreover, the CRF, opioid, leptin and ghrelin
      mechanisms operate collectively at the HPA axis and express the physiological and
      psychological components of AN. Fear conditioning is an intricate learning
      process occurring at the level of the hippocampus, amygdala, lateral septum and
      the dorsal raphe by involving three distinct pathways, the HPA axis-independent
      pathway, hypercortisolemia and ghrelin. Opioids mediate CRF through noradrenergic
      stimulation in association with the locus coeruleus. Furthermore, CRF's
      inhibitory effect on gonadotropin releasing hormone can be further explained by
      the direct relationship seen between CRF and opioids. Low levels of gonadotropin
      have been demonstrated in AN where only estrogen has shown to mediate energy
      intake. In addition, estrogen is involved in regulating u receptor
      concentrations, but in turn both CRF and opioids regulate estrogen. Moreover,
      opioids and leptin are both an effect of AN, while many studies have demonstrated
      a causal relationship between CRF and anorexic behavior. Moreover, leptin,
      estrogen and ghrelin play a role as predictors of survival in starvation. Since
      both leptin and estrogen are associated with higher levels of bone marrow fat
      they represent a longer survival than those who favor the ghrelin pathway. Future
      studies should consider cohort studies involving prepubertal males and females
      with high CRF. This would help prevent the extrapolation of results from studies
      on mice and draw more meaningful conclusions in humans. Studies should also
      consider these mechanisms in post-AN patients, as well as look into what
      predisposes certain individuals to develop AN. Finally, due to its complex
      pathogenesis the treatment of AN should focus on both the pharmacological and
      behavioral perspectives.

PMID- 22135623
TI  - Invasive Breast Cancer: Recognition of Molecular Subtypes.
AB  - SUMMARY: Molecular profiling has fundamentally changed our understanding of
      breast cancer in the last 10 years, by creating a new taxonomy of breast cancers
      based on the expression patterns of so-called 'intrinsic genes'. Hierarchical
      clustering analyses performed on microarray-based gene expression profiles of
      breast cancers defined distinct breast cancer subgroups (luminal type A/B, HER2
      enriched type, basal-like type). Since the initial landmark study by Perou et
      al., the concept of intrinsic breast cancer subtypes has been corroborated and
      expanded by several independent research groups. Further studies revealed
      individual properties of the intrinsic subgroups regarding the clinical course
      and the responsiveness to chemotherapy. The new gene expression profile-based
      taxonomy of breast cancer has been enthusiastically embraced by the scientific
      community and hailed as a major breakthrough on the way to individually tailored
      therapies. However, validation of the gene signatures in prospective studies is
      necessary before accepting these new technologies in daily clinical practice. In
      this review, the current data regarding the intrinsic subtypes and the associated
      clinical implications as well as the methodology of molecular profiling and
      possible use of immunohistochemistry in identifying intrinsic subtypes are
      discussed.

PMID- 22135624
TI  - Prediction of Response to Neoadjuvant Chemotherapy: New Biomarker Approaches and
      Concepts.
AB  - SUMMARY: About 10-25% of breast cancer patients achieve a pathologically
      confirmed complete response after neoadjuvant chemotherapy. Tissue samples of
      pretreatment core biopsies are a valuable resource for translational research
      aiming towards predictive biomarkers for selecting patients who are likely to
      benefit from neoadjuvant therapy. The German Breast Group (GBG) and the AGO-B
      Group (AGO = Working Group Gynecological Oncology) have extensive experience in
      conducting neoadjuvant clinical trials. Technologies as immunohistochemistry on
      tissue microarrays and standardized reverse transcription-polymerase chain
      reaction (RT-PCR) approaches on formalin-fixed paraffin-embedded samples allow
      high-throughput investigation of protein and mRNA biomarkers. With these
      approaches, we could demonstrate that molecular tumor subtypes and immunological
      infiltrates are valuable and independent predictors of therapy response. New
      biomarkers such as poly(ADPribose) polymerase (PARP) might be useful for the
      prediction of response to conventional and new targeted therapies. This review
      summarizes current research projects focusing on biomarker discovery in the
      neoadjuvant setting.

PMID- 22135626
TI  - Physicians' Perceptions of Patients' Knowledge and Opinions Regarding Breast
      Cancer: Associations with Patient Education and Physician Numeracy.
AB  - SUMMARY: Background: The aim of this study was to assess physicians' perception
      of their patients' knowledge and opinions regarding regular screening, and the
      association of their perceptions with physician numeracy and patient education
      level. Methods: We carried out a survey study of 240 obstetrician-gynecologists.
      Results: Overall, 99.6% physicians perceive that their patients know that breast
      cancer is hereditary, 86.5% predicted that there is a gene mutation related to
      breast cancer, and 79.4% predicted that most breast cancer cases occur in women
      aged 50 years or greater. Physicians with less educated patients thought that
      their patients would not know about genetic screening, and physicians with more
      educated patients thought that their patients would know that mammography does
      not reduce the risk of getting breast cancer. A total of 66.0% of obstetrician
      gynecologists answered all 3 numeracy questions correctly. Less numerate
      physicians were more likely to indicate that their typical patient would agree
      with the statement about regular mammography screens than the more numerate
      physicians. Conclusions: Obstetrician-gynecologists expect that their patients
      know some things about breast cancer and not others. Some of the physicians'
      perceptions about patients differ based on numeracy.

PMID- 22135625
TI  - Triple-Negative Breast Cancer: Clinical and Histological Correlations.
AB  - SUMMARY: Triple-negative breast cancer (TNBC) is characterized by the lack of
      estrogen and progesterone receptors and the lack of HER2 expression or
      amplification. Much interest has recently been focused on these triple-negative
      (TN) subtypes because they may be aggressive and are more likely to recur and
      metastasize than other subtypes of breast cancer. TNBC accounts for approximately
      10-24% of all breast cancer cases, and typically it occurs in younger patients
      and in patients with BRCA1 mutation. There is a substantial heterogeneity of
      TNBCs both at the morphological and the molecular level, but there are also
      common features, such as low tumor grade and accelerated tumor proliferation.
      Morphologically, TNBC may present as invasive ductal, metaplastic, medullary,
      apocrine, or other types. Molecularly, they are most frequently associated with a
      basal phenotype, but there is a distinct subgroup of cancers that are not of
      basal type and belong to the claudin-low or molecular-apocrine type. The basal
      phenotype is frequently associated with the loss of BRCA1.

PMID- 22135627
TI  - Liver alveolar echinococcosis metastasized to the breast.
AB  - BACKGROUND: Alveolar echinococcosis (AE) is a potentially fatal and chronically
      progressive infestation produced by the multivesicular metacestode of
      Echinococcus multilocularis, which most commonly affects the liver, lungs, and
      brain. CASE REPORT: We present a case of AE in which an alveolar cyst, as a
      result of exophytic growth, adhered to intra-abdominal and pelvic organs and
      metastasized to the breast. Exploration showed that the exophytic cyst in the
      liver filled the entire abdominal cavity, reaching to the uterus and bladder, and
      was adherent to the neighboring tissues and organs. This cystic lesion was
      totally excised, as was the 7*6 cm cystic lesion in the right breast.
      CONCLUSIONS: The liver is the most common site for echinococcal cysts of the
      pastoral strains (>65%), followed by the lungs (25%); the cyst is seen less
      frequently in the spleen, kidneys, heart, bone, and central nervous system. AE
      must be considered in areas where liver cysts are endemic and in the presence of
      a liver cyst, and the organs where a metastasis is possible must be thoroughly
      investigated. Furthermore, in these areas, when cystic disorders of the breast
      are present, AE should not be discounted among possible definitive diagnoses.

PMID- 22135628
TI  - Mucoepidermoid carcinoma in a breast affected by burn scars: comprehensive
      literature review and case report.
AB  - SUMMARY:  BACKGROUND: Mucoepidermoid carcinoma (MEC), which is primarily found in
      the salivary glands, is rarely seen in the breast. These tumors usually develop
      from squamous and mucus-secreting cells. Histological grading is an important
      prognostic factor. CASE REPORT: We present herein a case of a 69-year-old female
      patient with a painful mass in the left breast. Of importance is that, in
      addition to MEC, the patient had a wide area of scar tissue secondary to a burn
      that completely occupied the left bottom quadrant of the abdomen and retracted
      the left nipple up to the left upper quadrant. Fine needle aspiration biopsy was
      negative, and a lumpectomy was performed. Because the pathology results were
      consistent with MEC, modified radical mastectomy with subsequent adjuvant
      chemotherapy and radiotherapy was performed. The patient remained disease-free
      for 12 months after the treatment. In addition to a discussion of this case, we
      performed a review of the clinicopathological characteristics of 30 cases with
      breast MEC reported in the English language literature between 1979 and 2010.
      CONCLUSIONS: MEC of the breast is a rarely seen tumor, and this is the first
      report of MEC in a breast affected by burn scars.

PMID- 22135629
TI  - A Case of Metastatic Extramammary Paget's Disease Responding to Trastuzumab plus
      Paclitaxel Combination Therapy.
AB  - There is no effective treatment for advanced extramammary Paget's disease (EMPD).
      The human epidermal growth factor receptor 2 (HER2) protein is often
      overexpressed in EMPD. Trastuzumab is a humanized monoclonal antibody against
      HER2 used in the treatment of breast cancers in which HER2 is overexpressed. We
      report a case of advanced EMPD in which trastuzumab and paclitaxel combination
      therapy was effective. The patient was a 70-year-old Japanese woman who presented
      with EMPD on the vulva and multiple metastatic lymph nodes. Immunohistochemical
      staining revealed strong HER2 protein expression in the primary tumor and
      metastatic lymph nodes. The patient received trastuzumab and paclitaxel. After 4
      courses of this regimen, the mass on the vulva and the metastatic lymph nodes
      regressed. Our findings may imply that trastuzumab plus paclitaxel combination
      therapy is useful for the treatment of advanced EMPD overexpressing HER2.

PMID- 22135630
TI  - The ADMA-Metformin Hypothesis: Linking the Cardiovascular Consequences of the
      Metabolic Syndrome and Type 2 Diabetes.
AB  - Metformin and asymmetric dimethylarginine (ADMA) are structural analogs. They
      have opposite effects at multiple points on complex signaling pathways that
      coordinate energy, molecular synthesis, growth, and metabolism with nutrient
      intake. Excess saturated fats and glucose may initiate the methylation of
      arginine residues in proteins involved in the transcription of genes mediating
      inflammation, cell proliferation, apoptosis, and oncogenesis. Free ADMA may
      appear in the circulation after proteolysis of these proteins when the work of
      transcription is complete and ADMA subsequently functions as a signaling
      molecule. In children, ADMA levels are not significantly related to the usual
      metabolic syndrome risk factors but instead there is a significant association
      between ADMA and alkaline phosphatase - a marker of normal growth. There is only
      one direct study that shows that ADMA negates the metabolic effects of metformin.
      There are no investigations that demonstrate that metformin blocks the effect of
      ADMA and so this review must be considered hypothesis generating. The potential
      implications of the metformin-ADMA relationship merit further investigation.

PMID- 22135631
TI  - A Case for Early Screening for Diabetic Kidney Disease.
AB  - Chronic kidney disease (CKD) is a public health dilemma contributing to
      increasing global morbidity and mortality. There is increasing recognition that
      early detection and management of CKD is critical in delaying disease progression
      as well as improving mortality rates. However, kidney disease is a silent process
      and usually goes undetected until more advanced stages, wherein the opportunity
      to intervene and improve kidney-related outcome is diminished, since awareness of
      CKD is low in earlier stages. Herein, we will review the screening and detection
      strategies for CKD as well as the importance of intervention in early stages to
      reduce progression and also the burden of CKD.

PMID- 22135632
TI  - From Mycobacterium bovis, oxidative stress and HIV to brucellosis.

PMID- 22135633
TI  - Socio-demographic determinants of stigma among patients with pulmonary
      tuberculosis in Lagos, Nigeria.
AB  - BACKGROUND: Patients living with tuberculosis (TB) experience significant
      disruption of their social life and are exposed to stigma and discrimination.
      This situation impacts on treatment adherence by individual patients and on
      disease control especially in developing nations. Different aetiological
      propositions have been propounded, including the relationship of tuberculosis
      with the Acquired Immune Deficiency Syndrome (AIDS). OBJECTIVES: We sought to
      evaluate self-reported stigma experience among TB patients in Lagos and examine
      its socio-demographic determinants. METHOD: This was a descriptive cross
      sectional study, recruiting 205 patients on treatment at two government-owned
      referral centres for tuberculosis, using self-administered questionnaires to
      collect each respondent's data. RESULT: Eighteen percent reported a previous
      stigma experience. Stigma experience was observed to be significantly determined
      by age, low socio-economic status, level of education below secondary level,
      disclosure of status, history of weight loss, previous smoking and alcohol
      history. Also, patients unable to work on clinic days were more likely to
      experience stigma. Sex, religion, marital status and ethnicity were not
      significant determinants. CONCLUSION: Experience of stigma among patients with
      tuberculosis is common and may adversely affect treatment adherence. Healthcare
      workers and policy makers need to pay closer attention to the identified
      determinants for effective tuberculosis control.

PMID- 22135634
TI  - Predictors of treatment failure among pulmonary tuberculosis patients in Mulago
      hospital, Uganda.
AB  - INTRODUCTION: Early identification of Tuberculosis (TB) treatment failure using
      cost effective means is urgently needed in developing nations. The study set out
      to describe affordable predictors of TB treatment failure in an African setting.
      OBJECTIVE: To determine the predictors of treatment failure among patients with
      sputum smear positive pulmonary TB at Mulago hospital. The study was carried out
      in the TB clinic of Mulago hospital Kampala, Uganda. This was an unmatched case
      control study where fifty patients with a diagnosis of TB treatment failure
      (cases) and 100 patients declared cured after completing anti TB treatment
      (controls) were recruited into the study. Cases were compared with controls to
      determine predictors of treatment failure. RESULTS: Significant predictors of
      treatment failure in this study included a positive sputum smear at 2 months of
      TB treatment (OR 20.63, 95%CI 5.42- 78.41) and poor adherence to anti TB
      treatment (OR 14.59, 95%CI 3.04-70.15). CONCLUSION: This study identified a
      treatment related and a simple laboratory predictor of TB treatment failure in
      Mulago hospital which may be used in resource limited settings for early
      recognition of those at risk and early intervention.

PMID- 22135635
TI  - Pulmonary involvement of Brucellosis: a report of six cases.
AB  - BACKGROUND: Pulmonary involvement of brucellosis rarely occurs due to inhalation
      of infected aerosol or hematogenous overspreading. OBJECTIVE: The study aimed to
      reveal the pulmonary manifestations of brucellosis that occur rarely in Brucella
      infections in the context of six cases in this report. METHODS: Between 1998
      2008, 82 patients with brucellosis treated and followed up at infectious diseases
      clinic have been retrospectively studied in relation to their clinical and
      laboratory findings and treatment results. RESULTS: Patients' (n=6) age ranged
      from 48 to 59 years and they showed equal gender distribution. All patients
      presented with fever and cough. Radiological examination showed pneumonic patches
      and consolidation in two cases, bilateral glass round opacity in four cases,
      perivascular and peribronchial thickness increase in two cases, pleural effusion
      in two cases, sentri-acinar emphysematous images in one patient, and athelectasis
      in one patient. Blood cultures of three patients grew Brucella spp. All patients
      responded to treatment containing doxycycline, rifampicin and streptomycin (for
      only one patient) within seven to 10 days and were treated for six weeks except
      for one patient for who was treated eight weeks due to hepatosplenic brucellosis.
      CONCLUSION: Pulmonary involvement of brucellosis has good prognosis with combined
      antimicrobial therapy.

PMID- 22135636
TI  - Poverty, child sexual abuse and HIV in the Transkei region, South Africa.
AB  - Everyone love children. They want them to be happy and prosperous, but poverty
      takes away their rights. Poverty even forces them to sell their daughters in
      exchange for money. The trio of poverty, sexual assaults and HIV are
      complimentary to one another.This paper is a selection of 5 cases who presented
      at Sinawe Center as victims of rape, where money has played a role in the delay
      in reporting to the police. First, a young girl of 13 years was raped by a known
      person. The cost of settlement was a mere R500 (equivalent to 70 US dollars). The
      second victim was paid R10 or R20 for each sexual act. Third, fourth and fifth
      cases, were young girls who were forced to marry by their parents. The history,
      physical examination and laboratory investigations are given. Psychosocial and
      economic aspects are also discussed.

PMID- 22135637
TI  - Evaluation of oxidative status in patients with Fasciola hepatica infection.
AB  - BACKGROUND: F. hepatica infection is rare and mostly subclinical. Migration of
      juvenile forms of F. hepatica into the host's liver is accompanied by an
      inflammatory reaction followed by fibrosis and cirrhosis. OBJECTIVE: The aim of
      this study was to evaluate oxidative status by using a novel automated method in
      patients with Fasciola hepatica. METHODS: Twenty two patients with a diagnosis of
      F. hepatica and 26 healthy volunteers were enrolled in the study. Their Total
      antioxidant capacity status (TAC), total oxidant status (TOS) and catalase were
      measured in them and oxidative stress index (OSI) was calculated. These
      measurements were also taken for the control group and the values were compared.
      RESULTS: Plasma levels of total TOS and OSI were significantly increased in
      patients as compared with healthy controls (P<0.001, P<0.001, P=0.001, P=0.008)
      respectively. In contrast, TAC level was significantly lower in patients as
      compared with controls (p<0.05). There was no significant difference between the
      catalase results of the two groups (p>0.05). CONCLUSION: Total oxidative status
      and OSI were increased and total antioxidative status capacity was decreased in
      patients with F. hepatica infection. A high oxidative stress occurs during F.
      hepatica infection, which may cause severe damage in both the liver.

PMID- 22135638
TI  - Isolation and molecular characterisation of Mycobacterium bovis from raw milk in
      Tunisia.
AB  - BACKGROUND: Consumption of raw milk and unpasteurized dairy products is common in
      Tunisia where bovine tuberculosis remains enzootic. We herein investigated the
      frequency of M. bovis isolation from raw milk. METHODS: Three hundred and six
      milk samples collected from 102 infected cows in different Tunisian regions were
      analysed. M. bovis isolates were further characterized by spoligotyping and
      variable number tandem repeat typing. RESULTS: A total of five (4.9 %) M. bovis
      strains exhibiting three different genotypes were isolated. CONCLUSION: This
      study demonstrates that consumers of raw milk or derivatives in Tunisia are at
      high risk of zoonotic infection with M. bovis.

PMID- 22135639
TI  - Hepatitis B virus and HIV infection among patients with primary hepatocellular
      carcinoma in Kampala, Uganda.
AB  - BACKGROUND: Hepatitis B virus (HBV) is the commonest cause of primary
      hepatocellular (PHC) carcinoma worldwide. Co-infection with the HIV leads to more
      rapid progression of liver disease. OBJECTIVES: We described prevalence of HBV
      and HIV among patients with PHC admitted to Mulago Hospital, Kampala, Uganda.
      METHODS: We assessed all patients admitted to the gastrointestinal service of
      Mulago hospital with a diagnosis of PHC for HBV and HIV infection. RESULTS: From
      March to June 2008, we recruited 15 patients. Nine (60%) were male; the overall
      median age was 32 years (IQR 15 -67), with median ages for male and female 33 and
      36 years respectively. Alanine aminotransferase, aspartate aminotransferase,
      alkaline phosphatase and AFP were all elevated with median values of 57.5 IU/L,
      222 IU/L, 392 IU/L and 362 ng/ml respectively (IQR 14-145, 49-393, 165-1294 and 7
      480). Eight (53%) patients were from North and Northeastern Uganda. The HBsAg was
      reactive in 13(87%) patients and HIV in 3(20%), all of whom were also co-infected
      with HBV. CONCLUSION: There is high prevalence of HBV and HBV/HIV co-infection
      among patients with PHC in Uganda with high mortality. Reduction in incidence and
      mortality due to PHC in Uganda will require urgent large scale HBV vaccination.

PMID- 22135640
TI  - Prevalence of intestinal parasitic infections among HIV/AIDS patients from two
      health institutions in Abuja, Nigeria.
AB  - BACKGROUND: Intestinal parasitic infections play a vital role in the prognosis of
      HIV/AIDS in patients. OBJECTIVES: The aim of this study was to determine the
      prevalence of intestinal parasitic infections (IPIs) in HIV-infected individuals
      in two health facilities in Abuja-Nigeria. METHODS: A cross sectional study was
      conducted in two sites: the GEDE AIDS and Infectious Diseases Research Institute
      (GAIDRI), and the Human Virology Institute-General Hospital Asokoro-Abuja,
      Nigeria. A total of 119 subjects were recruited (85 HIV infected and 34 HIV
      negative). Stool specimens collected were analyzed macroscopically and
      microscopically for consistency and the presence of enteric parasites. RESULTS:
      The overall prevalence rate of enteroparasites obtained in this study was 22.7%
      (27/119). The prevalence of intestinal parasitic infections in HIV infected
      patients was 24.7 %; while in HIV negative persons, it was 17.6%. However, the
      high rate obtained for HIV infected patients was not statistically significant
      (p> 0.05). CONCLUSION: Although the prevalence rate of enteric parasites in
      HIV/AIDS patients was higher than in HIV negative individuals, this difference is
      not statistically significant. Even though there was no statistical difference in
      the two groups, parasitic infections in HIV/AIDS patients often result in
      debilitating illness.

PMID- 22135641
TI  - Renal disease in HIV infected patients at University of Benin Teaching Hospital
      in Nigeria.
AB  - BACKGROUND: HIV related renal disease is a common occurrence in patients with HIV
      infection. It is the third leading cause of end stage renal disease among African
      American males between the ages of 20 and 64 years in USA. Renal function
      impairment has been reported at all stages of HIV infection. The aim of this
      study is to determine the relationship between severity of renal function
      impairment and CD4 cell count in HIV infected patients. METHOD: HIV patients
      presenting at University of Benin Teaching Hospital Benin, City Nigeria from
      1(st) January to 30(th) June 2007 were randomly selected and screened for renal
      functional impairment (RFI). Those with RFI detected by glomerular filtration
      rate < 60 ml/min/1.73 m(2) or urine protein creatinine ratio 3 200 were
      stratified into mild, moderate and severe RFI. Forty patients from each stratum
      and forty HIV infected patients with normal renal functions were recruited as
      subjects and control respectively. Their clinical and laboratory parameters were
      evaluated. The data obtained were analysed using SPSS vs 15.0. RESULTS: Of the
      HIV patients screened, 53.3% had renal functional impairment. of these, 40.2% had
      mild, 37.7% had moderate and 22.2% had severe impairment in their renal functions
      respectively Their mean age was 36.0 +/- 8.8 years. The CD4 cell count was found
      to be 309.75 +/- 268.71/ul, 188.45 +/- 173.12/ul, and 141.10 +/- 126.01/ul among
      subjects with mild, moderate and severe RFI respectively. The CD4 cell count in
      control group was 319.05 +/- 248.41/ul. The difference was statistically
      significant. (p = <0.001). CD4 cell count had a significant positive correlation
      with GFR (r = 0.32, p = 0.042). However, there was a negative correlation between
      CD4 cell count and proteinuria but this was not statistically significant (r =
      0.09, p = 0.173). CONCLUSION: Severity of RFI has a positive correlation with
      degree of immunosuppression in HIV infected patients.

PMID- 22135642
TI  - Antibiotic susceptibility of Staphylococcus aureus in suppurative lesions in
      Lacor Hospital, Uganda.
AB  - BACKGROUND: Staphylococcus aureus, a mainly acquired hospital infection is
      responsible for many suppurative lesions and has demonstrated the ability of
      developing resistance to many antimicrobial agents leading to life threatening
      infections and long hospital stay. OBJECTIVE: To determined the prevalence and
      antibiotic susceptibility of Staphylococcus aureus in suppurative lesions of the
      surgical ward and outpatients of Lacor Hospital (Uganda). METHODS: A cross
      sectional study was conducted at St. Mary's Hospital Lacor to determine the
      prevalence and antibiotic susceptibility profiles of Staphylococcus aureus in
      suppurative lesions in both surgical inpatients and outpatients. Using culture
      techniques on MacConkey and blood agar, Staphylococcus aureus was isolated based
      on the colonial characteristics and confirmed by Catalase and tube Coagulase
      tests. The antibiotic susceptibility test was done using Kirby-Buer disk
      diffusion method on 4% Salt Muellar Hinton II agar for the Methicillin and non
      salted Muellar Hinton II agar for the other antibiotics (NCCLS M100S9). RESULTS:
      The prevalence of Staphylococcus aureus in 122 patients sampled was 59.4% for the
      surgical inpatients and 48.3% for outpatients giving an average prevalence of
      53.9% for both groups of patients. The average antibiotic susceptibility patterns
      for the 8 antibiotic tested were: Ampicillin (75.0%), Chloramphenicol (34.4%),
      Ciprofloxacin (1.6%), Erythromycin (7.8%), Gentamycin (0%), Methicillin (1.6%),
      Tetracycline (45.3%) and Co-trimoxazole (50.0%). The resistance in surgical
      inpatients was significantly higher than outpatients (t=1299, p<0.05) and
      Methicillin resistance was confirmed by PCR. CONCLUSION: Staphylococcus aureus is
      highly prevalent and more resistant in inpatients. There is a higher risk of
      acquiring drug resistant staphylococcus aureus infection in inpatients of Lacor
      Hospital with a Methicillin resistance of 0% and 2.6% for out and inpatients
      respectively.

PMID- 22135643
TI  - Antimicrobial susceptibility patterns of E. coli from clinical sources in
      northeast Ethiopia.
AB  - BACKGROUND: Escherichia coli is the leading cause of urinary tract, ear, wound
      and other infections in humans. Increasing rates of antimicrobial resistance
      among E. coli is a growing concern worldwide. OBJECTIVES: The aim of this study
      was to determine the prevalence and antimicrobial susceptibility of E. coli from
      clinical samples. METHOD: A retrospective review of culture results of urine, ear
      discharge, pus swab from wounds, and eye discharge was done. A total of 3,149
      samples were analyzed for isolation and identification of bacteria and
      antimicrobial susceptibility testing. RESULTS: E. coli was isolated from 446
      (14.2%) samples. The highest isolation rate was obtained from urine samples 203
      (45.5%). High resistance rates to erythromycin (89.4%), amoxicillin (86.0%) and
      tetracycline (72.6%) were documented. However, significantly high degree of
      sensitivity rates to nitrofurantoin (96.4%), norflaxocin (90.6%), gentamicin
      (79.6%) and ciprofloxacin were recorded (p<0.001). Multiple antimicrobial
      resistances of 74.6% and increased resistance rates to all antimicrobials except
      ciprofloxacin were also recorded. CONCLUSION: E. coli isolates showed high rates
      of resistance to erythromycin, amoxicillin and tetracycline. Nitrofurantoin,
      norflaxocin, gentamicin and ciprofloxacin are considered appropriate for
      empirical treatment of E. coli in the study area. Regular monitoring of
      antimicrobial susceptibility is recommended.

PMID- 22135644
TI  - Bothersome lower urinary symptoms during pregnancy: a preliminary study using the
      International Consultation on Incontinence Questionnaire.
AB  - BACKGROUND: During pregnancy, many women suffer from lower urinary tract symptoms
      which they hardly report to their care providers. Measuring the prevalence of
      these symptoms has been difficult because of lack of uniform nomenclature and
      standardized tool. The updated nomenclature and the new ICIQ-FLUTS questionnaire
      offer an opportunity for assessment of these symptoms especially in developing
      countries. OBJECTIVE: This study aimed to establish the prevalence of bothersome
      lower urinary symptoms among pregnant women in Zaria, Nigeria. METHODS: This was
      a cross-sectional study in which the International Consultation on Incontinence
      Questionnaire on Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) was
      administered by trained interviewers to 204 consenting pregnant women aged 15 to
      42 years who were attending Antenatal care (ANC) at a tertiary health facility in
      Zaria, Nigeria. RESULTS: Storage phase symptoms (nocturia, urgency, daytime
      frequency and painful bladder) were common among respondents. Of these, nocturia
      was the commonest with 94.1% of the respondents reporting it. Voiding symptoms
      (hesitancy, straining to pass urine and interrupted stream) were also found.
      Interrupted stream was the commonest of these, occurring in 8.3% of respondents.
      Incontinence; stress (13.7%), urge (9.8%) and enuresis (1%) were found among the
      respondents. CONCLUSIONS: These findings show that diverse, bothersome forms of
      lower urinary tract symptoms are experienced by pregnant women in this
      environment and the ICIQ-FLUTS questionnaire is a helpful tool in identifying
      these symptoms.

PMID- 22135645
TI  - Prescribing practices for malaria in a rural Ugandan hospital: evaluation of a
      new malaria treatment policy.
AB  - BACKGROUND: Increasing resistance to first line antimalarial drugs led to a
      change in the antimalarial policy of Uganda in 2005. Successful implementation of
      this policy depends on changing prescribing patterns of health workers.
      OBJECTIVES: To describe prescribing patterns for malaria and associated factors
      in a rural Ugandan hospital following a change in antimalarial treatment policy
      from chloroquine plus sulphadoxine-pyrimethamine to artemisinin-based combination
      therapies. METHODS: From the outpatients register, 715 prescriptions for malaria
      were reviewed. Data was collected on patient demographics, prescriber factors and
      prescription patterns. Prescriptions were considered to conform to the new
      antimalarial policy if artemether-lumefantrine was prescribed for uncomplicated
      malaria or quinine for treatment failure or complicated malaria. RESULTS: The
      most frequently prescribed antimalarials for uncomplicated and complicated
      malaria were artemetherlumefantrine (n=564, 88.5%) and quinine (n=66, 84.6%)
      respectively. The proportion of prescriptions conforming to the new antimalarial
      treatment policy was 88.1% (n=630). Predictors of conformity were: duration in
      service of less than 6 years (OR=3.40. CI=1.24-9.33), prescriber's profession
      (OR=97.51, CI=27.29-348.34) and diagnosis of uncomplicated malaria (OR=10.13,
      CI=3.37-30.42). CONCLUSIONS: Adequate training and provision of information
      relevant to the needs of different cadres of health workers is needed to promote
      effective uptake of new treatment policies.

PMID- 22135646
TI  - Increased oxidative stress in patients with familial Mediterranean fever during
      attack period.
AB  - OBJECTIVES: We aimed to investigate the status of oxidant and antioxidants during
      attack period (AP) and attack free periods (AFP) in Familial Mediterranean fever
      (FMF) patients. METHODS: Measured the levels of malondialdehyde (MDA), protein
      carbonyl (PC), glutathione (GSH) and antioxidant vitamins (A,C and E) as well as
      the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in serum and
      whole blood of FMF patients in FMF-AP and FMF-AFP. RESULTS: Levels of MDA and PC
      were found significantly higher (p <0.05) both in serum and whole blood of FMF-AP
      group compared with other groups. The CAT and GSH-Px activities in FMF-AP group
      were found markedly lower (p <0.05) comparing to HC group. However, there were no
      statistically significant differences between the groups in terms of antioxidant
      vitamin levels. CONCLUSIONS: Our study demonstrated increased oxidative stress in
      patients with FMF during AP. Investigations are needed to establish the effect of
      antioxidant supplementation on FMF attack frequency and severity. We also suggest
      that these increased MDA and PC levels and decreased antioxidants may be used as
      supportive markers to differentiate AP from AFP. These conclusions need to be
      validated in further multicenter studies with high number of FMF patients.

PMID- 22135647
TI  - Patient satisfaction with health care services provided at HIV clinics at Amana
      and Muhimbili hospitals in Dar es Salaam.
AB  - BACKGROUND: Since the establishment of free HIV/AIDS care and treatment services
      in Tanzania a lot of research has been done to assess how health care providers
      discharge their duties in these clinics. Little research however has been done
      regarding satisfaction of HIV patients with free health care services provided.
      OBJECTIVES: To determine satisfaction of HIV patients with health care services
      provided at the HIV clinics and specifically, to determine patients' satisfaction
      with the general physical environment of the clinic and with services offered by
      doctors, nurses, laboratory, and pharmacy. METHODS: A cross-sectional study was
      conducted at Muhimbili National Hospital (MNH) and Amana hospital. A total of 375
      patients attending outpatient HIV clinics were selected randomly and interviewed
      using a questionnaire, after obtaining a verbal consent. Data collected was
      analyzed using Epi-info program version 6. RESULTS: Patients at Amana Hospital
      clinic were either very satisfied (44.3%) or satisfied (55.7%) and none were
      unsatisfied, while at MNH clinic 1.1% patients were very satisfied while (94.7%)
      were satisfied and (4.2%) were unsatisfied with health care services provided.
      Lack of privacy when consulting with doctors and the dispenser contributed to
      patients' unsatisfaction with the services. CONCLUSION: Most of the participants
      were satisfied with the services provided at the two clinics. However at MNH, a
      few patients were unsatisfied due to lack of privacy during consultation with
      doctors and with the pharmacy services.

PMID- 22135648
TI  - The influence of knowledge and sociodemographics on AIDS perception and sexual
      practices among secondary school students in Nigeria.
AB  - BACKGROUND: Recent trends show a disproportionate increase in new incidences of
      HIV infection among teenagers compared to other population segments. OBJECTIVES:
      This study assessed secondary school students' perception of AIDS epidemic, and
      the influence of sociodemographic variables and AIDS knowledge on their
      perception and sexual practices. METHODS: Nigerian teenagers (N=1143) were
      surveyed using a questionnaire that elicited information on their demographics,
      AIDS knowledge, perceptions and previous encounter with survivors, and sexual
      practices. RESULTS: Although AIDS epidemic was not a serious issue of concern to
      a substantial number of the students, they were knowledgeable on AIDS, and their
      perceptions on AIDS epidemics influenced their sexual practices. Female teenagers
      were more knowledgeable and concerned, and more frequently reported inexperience
      with sexual intercourse compared to their male counterparts. CONCLUSION: AIDS
      education and campaigns that foster the internalization of the seriousness of
      AIDS epidemics and arouse concern about them could enhance safe sexual practices
      among the youths.

PMID- 22135649
TI  - Condom social marketing program to prevent HIV/AIDS in post-conflict Liberia.
AB  - BACKGROUND: Youths in sub-Saharan Africa (SSA) account for a large burden of the
      global HIV/STI crises. As such, strategies directed at promoting behavioral
      modifications would be critical to reducing the prevalence of risky sexual
      behaviors among high risk adolescents in post-conflict environments. OBJECTIVES:
      This study describes a condom promotion strategy to prevent HIV/STIs among highly
      vulnerable urban youth in a post-conflict, resource-constrained environment via
      the provision of both male and female condoms to nontraditional venues like music
      and photo shops, ice cream parlors, money exchange centers and beauty salons.
      METHODS: Community members in the designated catchment areas volunteered their
      services and the use of their small businesses to support this endeavor. RESULTS:
      In this paper, we describe the condom promotion strategy and its implications
      within the context of a community-based participatory social marketing program to
      prevent risky sexual behaviors among highly vulnerable urban youth in a post
      conflict country. CONCLUSION: We postulate that this approach may likely increase
      condom use among urban youth in Monrovia, the capital city of Liberia.

PMID- 22135650
TI  - Social factors associated with pulmonary hydatid cyst in Aegean, Turkey.
AB  - BACKGROUND: Pulmonary hydatid cysts are caused by larval forms of the tapeworm
      Echinococcus granulosus. Hydatid disease, which is endemic in Turkey, is an
      important health problem in agricultural and stockbreeding areas where there are
      insufficient environmental health and preventive medicine services. Previous
      studies on this topic reported that hydatid disease was frequently associated
      with stockbreeding in rural areas. OBJECTIVES: In this retrospective clinical
      study, it is aimed to evaluate the social factors associated with pulmonary
      hydatid cyst in the Aegean region of Turkey. METHODS: Seventy-one pulmonary
      hydatid cyst cases reported between 1998 and 2010 in four hospitals in the Aegean
      region for which data were available on social and lifestyle factors were
      reviewed. RESULTS: In contrast to expectations, we found that pulmonary hydatid
      disease in the Aegean region was associated with city rather than rural life and
      with occupations other than stockbreeding. CONCLUSION: The findings are
      attributed to the presence of uncontrolled dogs in the city and urban
      environmental pollution. The offices of the public administration have a
      responsibility to inform citizens about the control of street animals,
      environmental health, and food hygiene.

PMID- 22135651
TI  - Reliability of scored patient generated subjective global assessment for
      nutritional status among HIV infected adults in TASO, Kampala.
AB  - OBJECTIVE: Establish the reliability of the scored Patient Generated-Subjective
      Global Assessment (PG-SGA) in determining nutritional status among Antiretroviral
      Therapy (ART) naive HIV-infected adults. METHODS: A descriptive, cross sectional
      study among outpatient medical clinics, in The AIDS Support Organization (TASO),
      Mulago Centre, Kampala, Uganda. The study group (n=217) consisted of male (n=60)
      and female (n=157) HIV patients (18-67 years). Purposive sampling was used.
      Anthropometry (weight, height, BMI), nutritional history (body weight, dietary
      intake, gastrointestinal symptoms, functional capacity and infections), and
      clinical status were assessed. Sensitivity and specificity of PG-SGA were
      determined using Receiver Operating Characteristic (ROC) curve. Data collection
      was done from April-May 2008. RESULTS: Only 12% of the subjects were underweight
      and over half (58.2%) had normal weight. The PG-SGA had low sensitivity (69.2%)
      and specificity (57.1%) at categorizing the risk for malnutrition indicated by
      BMI< 18.5. CONCLUSION: There was a high prevalence of malnutrition among the
      study group. Overall, this study indicated the PG-SGA could not adequately
      discriminate between underweight and normal patients. The tool was not reliable
      enough for determining nutritional status in this population.

PMID- 22135652
TI  - Feasibility of implementing recommendations to improve communicable diseases
      surveillance--a modified Delphi study.
AB  - BACKGROUND: Effective control of communicable diseases requires an effective
      disease surveillance system (CDSS) which provides information for action on
      priority communicable diseases. It is the basis for public health decision-making
      worldwide. Implementation of any public health recommendations for improving a
      disease surveillance system depends on the acceptability of such recommendations
      by the relevant stakeholders and the feasibility of implementing the
      recommendations in practice. OBJECTIVES: The aim of this study was to assess the
      acceptability and the feasibility of recommended improvements in CDSS among
      relevant stakeholders in Khartoum state. METHODS: A Delphi consensus process was
      used in the form of three analytical written rounds and individual face-to-face
      discussions among relevant stakeholders in Khartoum state to study the
      feasibility of the recommended improvements in CDSS in Khartoum state. RESULTS:
      The stakeholders in Khartoum state agreed with most of our statements to improve
      the CDSS core activities, supportive functions and quality in Khartoum State, and
      that the existing CDSS in Khartoum state needs to be strengthened with more
      effective coordination at different levels. Regarding the feasibility of
      implementing our recommendations, the results of our Delphi survey suggest
      neither expanding CDSS system, nor including vertical programmes; formulation of
      updated objectives; improving data management and feedback; strengthening
      epidemic management, as well as the quality of the system in terms of timeliness,
      completeness and acceptability. CONCLUSION: This study added strength to our
      recommendations, based on two previous studies assessing the CDSS in Khartoum
      state. The Ministry of Health in Khartoum state can implement our consensus
      recommendations to improve the CDSS system in the future in order to achieve its
      targeted goals.

PMID- 22135653
TI  - The lesser Egyptian jerboa, Jaculus jaculus: a unique rodent model for evolution
      and development.
AB  - Tetrapods that have evolved the ability to run or bound at great speeds over long
      distances have repeatedly converged on specific morphological limb adaptations,
      including the loss of lateral digits, elongation of limb segments, and fusion of
      individual elements. Many of the more familiar cursorial animals, such as horses
      and deer, are large and do not lend themselves well to experimental embryonic
      analyses. However, a group of lesser-known bipedal rodents, the three-toed
      jerboas, has become an exceptional model for studying the developmental and
      molecular mechanisms shaping these limb morphologies. The lesser Egyptian jerboa,
      Jaculus jaculus, represents the most derived subfamily of jerboas and shows loss
      of the anterior and posterior hindlimb digits, fusion of the three central
      metatarsals, and dramatic elongation of the hindlimb relative to the forelimb
      with disproportionate elongation of the metatarsals. In addition, several unique
      physiological and morphological characteristics make these excellent animals for
      evolutionary studies. As small docile rodents, they are amenable to rearing in a
      laboratory setting and, along with several related species with a variety of
      skeletal morphologies, are plentiful enough in the wild to support field
      collections. The close evolutionary relationship to Mus musculus and the
      development of genomic resources for J. jaculus support comparative developmental
      and molecular analyses.

PMID- 22135654
TI  - Husbandry and breeding of the lesser Egyptian Jerboa, Jaculus jaculus.
AB  - The lesser Egyptian jerboa, Jaculus jaculus, is the ideal jerboa species for use
      as a laboratory model system. As a member of the most derived clade of three-toed
      jerboas, it shows all of the specialized characteristics for bipedalism,
      including loss of the lateral digits and fusion and elongation of the
      metatarsals. It is a small rodent, weighing ~55 g as an adult, and it does not
      hibernate through the winter as is common with many other jerboa species. It is
      the first Dipodoid rodent whose genome is to be sequenced, and multiple genomic
      resources are being generated. The jerboa has been notoriously difficult to breed
      in captivity with only a small number of zoos and private breeders achieving
      success. The Harvard University colony of 60 adult animals (half male/half
      female) has had 36 offspring born in captivity in one year. The jerboa colony at
      the Breeding Centre for Endangered Arabian Wildlife in Sharjah, UAE has been
      operating since 2007 and has had 180 live births. Here, we outline guidelines for
      successfully maintaining and breeding a colony of J. jaculus in a laboratory
      setting.

PMID- 22135655
TI  - Dissection of adult Drosophila brains.
AB  - The Drosophila nervous system provides a valuable model for studying various
      aspects of brain development and function. The postembryonic Drosophila brain is
      especially useful, because specific neuron types derive from specific progenitors
      at particular times. Elucidating the means by which diverse neuron types derive
      from a limited number of progenitors can contribute significantly to our
      understanding of the genetic and molecular mechanisms involved in developmental
      neurobiology. This protocol describes general procedures for dissecting the brain
      and ventral nerve cord (VNC) of adult Drosophila. The dissected tissues are
      suitable for further analysis, e.g., by any number of labeling techniques.

PMID- 22135656
TI  - Fragmentation and labeling of probe DNA for whole-mount FISH in Drosophila.
AB  - Good probes for whole-mount fluorescent in situ hybridization (FISH) must meet
      two criteria: The DNA fragments must be very small and they must be highly
      labeled. This article describes an effective labeling scheme that involves
      fragmenting the probe DNA and then adding a mixture of labeled and unlabeled
      nucleotides to the 3' ends using the enzyme terminal deoxynucleotidyl transferase
      (TdT). This method can be used to label a variety of DNA probes, regardless of
      their initial size (e.g., plasmid, cosmid, or P1 clones, polymerase chain
      reaction [PCR] products, or total genomic DNA). Short oligonucleotides may also
      be labeled in this way without digestion, because their small size allows them to
      diffuse through thick tissues. A potential advantage of end-labeling is that the
      modified nucleotides are not incorporated into the complementary probe sequence
      itself and may thus interfere less with hybridization. The free 3' tail may also
      make haptens more accessible to detection reagents.

PMID- 22135657
TI  - Manual dissection and fixation of Drosophila egg chambers for whole-mount FISH.
AB  - This article describes a procedure for the manual dissection and fixation of
      Drosophila egg chambers for whole-mount fluorescent in situ hybridization (FISH).
      Egg chambers are more challenging to fix than embryos. They are easily overfixed
      so that probes will not penetrate well into the oocyte nucleus, even if some
      hybridization is detected in the follicle and nurse cells closer to the surface.
      If late-stage oocytes are to be examined, the tissue must also be protected
      against osmotic shock before and during fixation, because this will activate
      metaphase-arrested nuclei to undergo the metaphase-anaphase transition. Warming
      the buffered formaldehyde to 30 degrees C immediately prior to fixation tends to
      enhance probe penetration. In contrast to reported results with immunostaining,
      FISH is equally successful whether fixation is performed with freshly prepared
      formaldehyde or commercial formaldehyde solutions. Manual dissection of fixed
      ovarioles gives a much higher yield per adult than the blender technique
      (facilitating analysis of mutants), and younger egg chambers in particular will
      be enriched, although the procedure itself is more laborious.

PMID- 22135658
TI  - Hybridization to tissues in suspension for whole-mount FISH in Drosophila.
AB  - Hybridization to some Drosophila tissues, such as embryos or egg chambers, is
      easily performed in suspension. The reaction is set up in 0.5-mL polymerase chain
      reaction (PCR) tubes and the solutions are changed by allowing the tissue to
      settle to the bottom of the tube, aspirating the liquid carefully, and replacing
      it with 400-500 uL of a new solution. This is by far the most convenient way to
      perform the hybridization and requires a minimum volume for all washing steps.
      The denaturation step is also easy to perform consistently because the sample can
      be heated and annealed in a thermal cycler or conventional water bath. This
      protocol describes hybridization to tissues in suspension for whole-mount
      fluorescent in situ hybridization (FISH) in Drosophila.

PMID- 22135659
TI  - Single fly tethered paradigms.
AB  - The most successful approaches for studying visual perception and visual learning
      in Drosophila have been single fly paradigms in which tethered individuals
      respond to different visual stimuli, as described here. The equipment and
      protocols involved are quite sophisticated and differ depending on whether
      behavior or electrophysiology will be pursued. For either approach, flies must
      first be secured to a metal wire. This is typically performed by first cooling
      flies down to 4 degrees C and then gluing them to a copper or tungsten wire with
      ultraviolet (UV)-activated cement. For electrophysiology, tethering requires a
      few extra steps to accommodate the placement of electrodes. Prepared individuals
      are then placed inside a cylindrical arena where images can be presented, or in
      front of a computer screen or even in front of a laptop. Flight dynamics or brain
      activity in response to visual stimuli is recorded by using a variety of
      specialized and/or commercially available electronic devices.

PMID- 22135660
TI  - Forensic DNA testing.
AB  - Forensic DNA testing has a number of applications, including parentage testing,
      identifying human remains from natural or man-made disasters or terrorist
      attacks, and solving crimes. This article provides background information
      followed by an overview of the process of forensic DNA testing, including sample
      collection, DNA extraction, PCR amplification, short tandem repeat (STR) allele
      separation and sizing, typing and profile interpretation, statistical analysis,
      and quality assurance. The article concludes with discussions of possible
      problems with the data and other forensic DNA testing techniques.

PMID- 22135661
TI  - Methods for imaging thick specimens: confocal microscopy, deconvolution, and
      structured illumination.
AB  - When a thick specimen is viewed through a conventional microscope, one sees the
      sum of a sharp image of an in-focus region plus blurred images of all of the out
      of-focus regions. High background, scattering, and aberrations are all problems
      when viewing thick specimens. Several methods are available to deal with these
      problems in living samples. These methods can be grouped into three classes:
      primarily optical (e.g., confocal microscopy, multiphoton microscopy), primarily
      computational (e.g., deconvolution techniques), and mixed (e.g., structured
      illumination) approaches. This article describes these techniques, which make it
      possible to see details within thick specimens (e.g., the interiors of cells
      within living tissue) by optical sectioning, without the artifacts associated
      with physically sectioning the specimen.

PMID- 22135662
TI  - Production of recombinant Herpesvirus saimiri-based vectors.
AB  - Herpesvirus saimiri (HVS) is capable of infecting a range of human cell types
      with high efficiency. The viral genome persists as high-copy-number, circular,
      nonintegrated episomes that segregate to progeny upon cell division. This allows
      HVS-based vectors to transduce stably a dividing cell population and provide
      sustained transgene expression for an extended period of time both in vitro and
      in vivo. Moreover, the insertion of a bacterial artificial chromosome (BAC)
      cassette into the HVS genome simplifies the incorporation of large amounts of
      heterologous DNA for gene delivery. These properties offer characteristics
      similar to that of an artificial chromosome combined with an efficient delivery
      system. To insert and express a heterologous gene in an HVS-based vector, a
      recombinant virus must be constructed, as described in this protocol. An HVS-BAC
      is used to simplify and enhance the production of recombinant viruses. This
      requires a two-step process to insert the heterologous expression cassette first
      into the pHVS-Shuttle and then into the HVS-BAC.

PMID- 22135663
TI  - Assessment of infectivity using a Herpesvirus saimiri (HVS) recombinant that
      expresses HVS-GFP.
AB  - Herpesvirus saimiri (HVS) is capable of infecting a wide range of human cell
      types with high efficiency. The viral genome persists as high-copy-number,
      circular, nonintegrated episomes that segregate to progeny on cell division. This
      allows HVS-based vectors to transduce stably a dividing cell population and
      provide sustained transgene expression for an extended period of time both in
      vitro and in vivo. Moreover, the insertion of a bacterial artificial chromosome
      (BAC) cassette into the HVS genome simplifies the incorporation of large amounts
      of heterologous DNA for gene delivery. These properties offer characteristics
      similar to that of an artificial chromosome combined with an efficient delivery
      system. This protocol describes the use of an HVS recombinant virus expressing
      green fluorescent protein (GFP) (HVS-GFP) to assess the infectivity of a specific
      cell line.

PMID- 22135664
TI  - Gardella gel analysis to detect Herpesvirus saimiri episomal DNA.
AB  - Herpesvirus saimiri (HVS) is capable of infecting a range of human cell types
      with high efficiency. The viral genome persists as high-copy-number, circular,
      nonintegrated episomes that segregate to progeny on cell division. This allows
      HVS-based vectors to transduce stably a dividing cell population and provide
      sustained transgene expression for an extended period of time both in vitro and
      in vivo. Moreover, the insertion of a bacterial artificial chromosome (BAC)
      cassette into the HVS genome simplifies the incorporation of large amounts of
      heterologous DNA for gene delivery. These properties offer characteristics
      similar to that of an artificial chromosome combined with an efficient delivery
      system. In this protocol, Gardella gel analysis is performed to determine whether
      the HVS genome is maintained in a nonintegrated episomal form. This method allows
      the identification of chromosomal/integrated DNA and episomal and linear forms of
      viral DNA, which run at the top, middle, and bottom of the gel, respectively. To
      obtain the required sensitivity to detect HVS episomes within host tissues, a
      modified polymerase chain reaction (PCR)-based Gardella gel can also be utilized.

PMID- 22135665
TI  - Single-molecule gold-nanoparticle tracking.
AB  - Gold nanoparticles, like single fluorophores, can be used to locate single
      molecules with nanometer accuracy. Unlike an optical trap, the gold particle
      label does not exert an external load, which is important for studying diffusive
      processes. Thus, a gold particle can be used analogously to a single fluorophore,
      providing similar information but with submillisecond time resolution. The
      features of gold-nanoparticle tracking (high temporal resolution, small label
      size, and lack of applied force) facilitate the characterization of structural
      properties of short-lived intermediates, as shown by our work with myosin V. This
      protocol provides details for gold-nanoparticle-tracking experiments, including
      flow cell construction, microscopy, and data analysis, along with a brief outline
      of actin and myosin preparation. Although details particular to our experiment
      are given, the approach should be generally applicable.

PMID- 22135666
TI  - Imaging synaptic inhibition with the genetically encoded chloride indicator
      Clomeleon.
AB  - Several techniques are available to image excitatory processes in the brain, but
      synaptic inhibition has remained largely invisible. Most synaptic inhibition in
      the brain arises from transmembrane fluxes of chloride ions (Cl(-)), so imaging
      intracellular Cl(-) concentration ([Cl(-)](i)) is, in principle, a natural way to
      visualize the spatiotemporal dynamics of inhibition. This protocol describes the
      use of Clomeleon, a genetically encoded indicator of Cl(-), as a tool for
      monitoring synaptic inhibition. It outlines procedures that can be used to image
      neuronal [Cl(-)](i) in brain slices prepared from Clomeleon transgenic mice. With
      only minor adjustments, the same procedures should be suitable for imaging from
      cultured cells as well.

PMID- 22135667
TI  - Preparation of samples for single-worm tracking.
AB  - Neurobiological research in genetically tractable organisms relies heavily on
      robust assays for behavioral phenotypes. The simple body plan of the nematode
      Caenorhabditis elegans makes it particularly amenable to the use of automated
      microscopy and image analysis to describe behavioral patterns quantitatively.
      This protocol first describes the preparation and use of media for growing and
      maintaining worms for tracking. The second part of the protocol describes how to
      prepare a single young adult worm for recording during video analysis. Although
      the protocol was developed for use in a single-worm tracker, it addresses factors
      important for the generation of reproducible, standardized images in all systems.

PMID- 22135668
TI  - Illumination for worm tracking and behavioral imaging.
AB  - Neurobiological research in genetically tractable organisms relies heavily on
      robust assays for behavioral phenotypes. The simple body plan of the nematode
      Caenorhabditis elegans makes it particularly amenable to the use of automated
      microscopy and image analysis to describe behavioral patterns quantitatively.
      This protocol provides an approach for obtaining uniform illumination during worm
      tracking. Good lighting can be more of an art than a science. Once the system is
      set up, it will be necessary to play with it, testing the results after each
      adjustment to ensure that the analysis software is able to clearly identify the
      worm and its boundaries. Although the protocol was developed for use in a single
      worm tracker, it addresses factors important for the generation of reproducible,
      standardized images in all systems.

PMID- 22135670
TI  - X-ray microtomographic imaging of intact vertebrate embryos.
AB  - X-ray microtomography (microCT) is a highly versatile imaging method, and with
      appropriate contrast stains and sample mounting, it can produce high-quality
      images of embryos at a wide range of developmental stages. The techniques
      presented here provide simple and robust methods for gel embedding and microCT
      scanning of vertebrate embryos. The specimens are fixed by any common method,
      contrast-stained with phosphotungstic acid (PTA, a common reagent in histological
      staining), and mounted in agarose gel for scanning. The gel mounting immobilizes
      the sample effectively during a long scan, and holds the embryo in its liquid
      medium (70% ethanol), allowing nondestructive three-dimensional (3D) imaging to
      be followed by, for example, histological processing. An alternative procedure is
      given for imaging resin-embedded samples intended for transmission electron
      microscopy (TEM) or subsequent sectioning and ultrastructural analysis. These
      procedures are expected to lend themselves well to quantitative analyses of
      mutant and experimental phenotypes and to generating accurate 3D anatomical data
      for embryological atlases.

PMID- 22135669
TI  - Tracking movement behavior of multiple worms on food.
AB  - Neurobiological research in genetically tractable organisms relies heavily on
      robust assays for behavioral phenotypes. The simple body plan of the nematode
      Caenorhabditis elegans makes it particularly amenable to the use of automated
      microscopy and image analysis to describe behavioral patterns quantitatively.
      Forward genetic screens and screens of drug libraries require high-throughput
      phenotyping, a task traditionally incompatible with manual scoring of
      quantitatively varying behaviors. High-throughput automated analysis of C.
      elegans movement behavior is now possible with several different tracking
      software packages. The Multiworm Tracker (MWT) described here is designed for
      high-throughput analysis: it can record dozens of worms simultaneously at 30
      frames per second for hours or days at a time. This is accomplished by performing
      all image analysis in real time, saving only the worm centroid, bearing, and
      outline data to the disk. To simplify image processing, the system focuses only
      on worms that have moved, and detects and discards worms that are touching rather
      than trying to isolate them computationally. Because the software is entirely
      automated, protocols can run unattended once the worms have been placed and the
      software has been started. The MWT does not save images for later analysis, but
      behavior can be validated manually with a companion analysis tool that replays
      recorded body postures. This protocol describes a basic basal movement assay on
      food using the MWT; similar protocols apply to related assays and to similar
      multiple animal trackers. The protocol can be extended to a variety of assays
      ranging from tap response to chemotaxis.

PMID- 22135671
TI  - Coating particles with carbocyanine dyes.
AB  - Imaging and reconstruction of developing neurons require cells that are labeled
      in a way that distinguishes them from their neighbors. This can be achieved with
      ballistic labeling, which refers to the delivery of a cell label by means of
      carrier particles (tungsten or gold) propelled from a pressurized gun. Ballistic
      delivery can reach many dispersed cells in one shot and can deploy a wide variety
      of cell markers to neurons in diverse preparations. The three most commonly used
      types of ballistic labels are carbocyanine dyes, dextran-conjugated fluorescent
      markers, and DNA plasmids. The primary advantage of ballistic labeling is that
      multiple dispersed cells can be labeled quickly in live or fixed tissue. This
      article describes a protocol for coating tungsten particles (~1 um in diameter)
      with carbocyanine dyes, which are widely used to label neurons in tissue and
      neural cells in suspension. These dyes are lipophilic and highly fluorescent
      within lipid bilayers. Because tissue damage worsens with the increasing pressure
      required for deeper bullet penetration, ballistic labeling of neurons is most
      effective when the target cells are near the surface of the preparation. This
      protocol was developed for labeling ganglion cells in retinal flat mounts.

PMID- 22135672
TI  - Shooting DNA, dyes, or indicators into tissue slices using the gene gun.
AB  - Imaging and reconstruction of developing neurons require cells that are labeled
      in a way that distinguishes them from their neighbors. This can be achieved with
      ballistic labeling, which refers to the delivery of a cell label by means of
      carrier particles (tungsten or gold) propelled from a pressurized gun. Ballistic
      delivery can reach many dispersed cells in one shot and can deploy a wide variety
      of cell markers to neurons in diverse preparations. The three most commonly used
      types of ballistic labels are carbocyanine dyes, dextran-conjugated fluorescent
      markers, and DNA plasmids. This article describes a protocol for using a Helios
      Gene Gun (Bio-Rad Laboratories) to inject coated particles into cells located
      near the surface of a tissue preparation. Shooting particles coated with
      carbocyanine dyes or dextran-conjugated fluorescent markers requires that a
      filter be placed between the gene gun and the target tissue. The filter prevents
      unbound dye clumps from reaching the tissue and attenuates the pressure wave
      reaching the tissue. DNA-coated particles can be shot without a filter if the
      target cells are located near enough to the surface (<20 MUm deep) for the
      particles to penetrate using low helium pressures (35-40 psi).

PMID- 22135673
TI  - Neuroprotective Mechanisms of PPARdelta: Modulation of Oxidative Stress and
      Inflammatory Processes.
AB  - Peroxisome proliferator-activated receptors (PPARalpha, delta, and gamma) are
      ligand-activated transcription factors that regulate a wide range of cellular
      processes, including inflammation, proliferation, differentiation, metabolism,
      and energy homeostasis. All three PPAR subtypes have been identified in the
      central nervous system (CNS) of rodents. While PPARalpha and PPARgamma are
      expressed in more restricted areas of the CNS, PPARdelta is ubiquitously
      expressed and is the predominant subtype. Although data regarding PPARdelta are
      limited, studies have demonstrated that administration of PPARdelta agonists
      confers neuroprotection following various acute and chronic injuries to the CNS,
      such as stroke, multiple sclerosis, and Alzheimer's disease. The antioxidant and
      anti-inflammatory properties of PPARdelta agonists are thought to underly their
      neuroprotective efficacy. This review will focus on the putative neuroprotective
      benefits of therapeutically targeting PPARdelta in the CNS, and specifically,
      highlight the antioxidant and anti-inflammatory functions of PPARdelta agonists.

PMID- 22135674
TI  - Atherogenic omega-6 Lipids Modulate PPAR- EGR-1 Crosstalk in Vascular Cells.
AB  - Atherogenic omega-6 lipids are physiological ligands of peroxisome proliferator
      activated receptors (PPARs) and elicit pro- and antiatherogenic responses in
      vascular cells. The objective of this study was to investigate if omega-6 lipids
      modulated the early growth response-1 (Egr-1)/PPAR crosstalk thereby altering
      vascular function. Rat aortic smooth muscle cells (RASMCs) were exposed to omega
      6 lipids, linoleic acid (LA), or its oxidized form, 13-HPODE (OxLA) in the
      presence or absence of a PPARalpha antagonist (MK886) or PPARgamma antagonist
      (GW9662) or PPAR-specific siRNA. Our results demonstrate that omega-6 lipids,
      induced Egr-1 and monocyte chemotactic protein-1 (MCP-1) mRNA and protein levels
      at the acute phase (1-4 hrs) when PPARalpha was downregulated and at subacute
      phase (4-12 hrs) by modulating PPARgamma, thus resulting in altered monocyte
      adhesion to RASMCs. We provide novel insights into the mechanism of action of
      omega-6 lipids on Egr-1/PPAR interactions in vascular cells and their potential
      in altering vascular function.

PMID- 22135676
TI  - Domoic Acid-Induced Neurotoxicity Is Mainly Mediated by the AMPA/KA Receptor:
      Comparison between Immature and Mature Primary Cultures of Neurons and Glial
      Cells from Rat Cerebellum.
AB  - Domoic acid (DomA) is a naturally occurring shellfish toxin that can induce brain
      damage in mammalians. Neonates have shown increased sensitivity to DomA-induced
      toxicity, and prenatal exposure has been associated with e.g. decreased brain
      GABA levels, and increased glutamate levels. Here, we evaluated DomA-induced
      toxicity in immature and mature primary cultures of neurons and glial cells from
      rat cerebellum by measuring the mRNA levels of selected genes. Moreover, we
      assessed if the induced toxicity was mediated by the activation of the AMPA/KA
      and/or the NMDA receptor. The expression of all studied neuronal markers was
      affected after DomA exposure in both immature and mature cultures. However, the
      mature cultures seemed to be more sensitive to the treatment, as the effects were
      observed at lower concentrations and at earlier time points than for the immature
      cultures. The DomA effects were completely prevented by the antagonist of the
      AMPA/KA receptor (NBQX), while the antagonist of the NMDA receptor (APV) partly
      blocked the DomA-induced effects. Interestingly, the DomA-induced effect was also
      partly prevented by the neurotransmitter GABA. DomA exposure also affected the
      mRNA levels of the astrocytic markers in mature cultures. These DomA-induced
      effects were reduced by the addition of NBQX, APV, and GABA.

PMID- 22135675
TI  - Thiazolidinediones on PPARgamma: The Roles in Bone Remodeling.
AB  - Thiazolidinediones (TZDs) are synthetic PPARgamma (peroxisome proliferator
      activated receptor gamma) agonists and a class of drugs for diabetes mellitus
      type 2 that can decrease blood sugar efficiently by enhancing insulin
      sensitivity. However, increased bone fracture risk in diabetic individuals
      treated with TZDs is one of the reported side effects. Recent studies show that
      TZDs such as rosiglitazone simultaneously inhibit osteoblast differentiation and
      activate osteoclast differentiation, leading to bone loss due to decreased bone
      formation and increased bone resorption. Furthermore, TZDs may activate PPARgamma
      in tissues other than bone, such as the hypothalamus-pituitary-gonad (HPG) axis
      to indirectly regulate bone mass. This paper will focus on current new
      developments that implicate potential mechanisms for how PPARgamma modulates
      skeletal homeostasis and how TZDs exert bone-loss side effects.

PMID- 22135677
TI  - "Down the language rabbit hole with alice": a case study of a deaf girl with a
      cochlear implant.
AB  - Alice, a deaf girl who was implanted after age three years of age was exposed to
      four weeks of storybook sessions conducted in American Sign Language (ASL) and
      speech (English). Two research questions were address: (1) how did she use her
      sign bimodal/bilingualism, codeswitching, and code mixing during reading
      activities and (2) what sign bilingual code-switching and code-mixing strategies
      did she use while attending to stories delivered under two treatments: ASL only
      and speech only. Retelling scores were collected to determine the type and
      frequency of her codeswitching/codemixing strategies between both languages after
      Alice was read to a story in ASL and in spoken English. Qualitative descriptive
      methods were utilized. Teacher, clinician and student transcripts of the reading
      and retelling sessions were recorded. Results showed Alice frequently used
      codeswitching and codeswitching strategies while retelling the stories retold
      under both treatments. Alice increased in her speech production retellings of the
      stories under both the ASL storyreading and spoken English-only reading of the
      story. The ASL storyreading did not decrease Alice's retelling scores in spoken
      English. Professionals are encouraged to consider the benefits of early sign
      bimodal/bilingualism to enhance the overall speech, language and reading
      proficiency of deaf children with cochlear implants.

PMID- 22135678
TI  - Quality of life in endometrial cancer survivors: what does obesity have to do
      with it?
AB  - Objective. Most women with type I endometrial cancer (EC) are obese, increasing
      the risk of morbidity and mortality in this population. The study objective was
      to evaluate the impact of obesity on quality of life (QOL) and general health
      status in EC survivors with early-stage disease. Methods. A prospective ancillary
      analysis of stage I/II EC survivors. The association of BMI with QOL
      questionnaire variables measured with the functional assessment of cancer therapy
      (subscales: physical (PWB), functional (FWB), social, and emotional well-being)
      and the physical (PCS) and mental component summary subscales of the short-form
      medical outcomes survey was determined. Results. 152 women completed both
      questionnaires; 81% were obese. After multiple linear regression, BMI was
      inversely associated with PWB (P = .001), FWB (P = 0.048), and PCS (P = .001).
      Conclusions. Despite the good prognosis associated with early-stage EC, QOL, and
      physical health are not optimized in obese survivors. This paper highlights the
      importance of incorporating health-related QOL assessments and obesity
      interventions during the survivorship period.

PMID- 22135679
TI  - Effect of Red Clover Isoflavones over Skin, Appendages, and Mucosal Status in
      Postmenopausal Women.
AB  - Objective. Evaluate in postmenopausal women the effect of red clover extract
      (RCE) isoflavones over subjective status of skin, appendages, and several mucosal
      sites. Method. Postmenopausal women (n = 109) were randomly assigned to receive
      either two daily capsules of the active compound (80 mg RCE, Group A) or placebo
      of equal appearance (Group B) for a 90-day period. After a washout period of 7
      days, medication was crossed over and taken for 90 days more. Subjective
      improvement of skin, appendages, and several mucosal site status was assessed for
      each studied group at 90 and 187 days using a visual analogue scale (VAS). In
      addition, libido, tiredness, and urinary, sleep, and mood complaints were also
      evaluated. Results. Women after RCE intervention (both groups) reported better
      subjective improvement of scalp hair and skin status, libido, mood, sleep, and
      tiredness. Improvement of urinary complaints, nail, body hair, and mucosa (oral,
      nasal, and ocular) status did not differ between treatment phases (intra- and
      intergroup). Overall satisfaction with treatment was reported higher after RCE
      intervention (both groups) as compared to placebo. Conclusion. RCE
      supplementation exerted a subject improvement of scalp hair and skin status as
      well as libido, mood, sleep, and tiredness in postmenopausal women.

PMID- 22135680
TI  - Surgical management of uterine fibroids at aminu kano teaching hospital.
AB  - Objective. To determine the influence of age and parity on the surgical
      management of uterine fibroids, clinical presentation, presence of pelvic
      adhesions, cadre of surgeons, and postoperative complications at the Aminu Kano
      Teaching Hospital, Kano, Nigeria. Methods. A retrospective analysis of 105 cases
      of uterine fibroids that were managed between 1st January 2003 and 31st December
      2007. Results. The period prevalence of uterine fibroids was 24.7% of all major
      gynecological operations. The mean age was 35.8 +/- 7.6 and mean parity 4.7 +/-
      2.8. Abdominal hysterectomy accounted for 58.1% of the cases and myomectomy
      41.9%. The odd of using abdominal hysterectomy was about twice that of
      myomectomy. Pelvic adhesions were found in 67.6% of the cases. Menorrhagia
      (86.7%) was the commonest symptom, while post operative anemia and pyrexia showed
      significant association with myomectomy. There was no maternal mortality.
      Conclusion. Surgical operations for uterine fibroids are safe and common kind of
      gynecological operations at the Aminu Kano Teaching Hospital. Uterine fibroid is
      associated more with high parity and dominance of abdominal hysterectomy over
      myomectomy, because early girl marriage is common in our community.

PMID- 22135681
TI  - Indications and outcomes of uterine artery embolization in patients with uterine
      leiomyomas.
AB  - Objective. To investigate the indication and limitations of uterine artery
      embolization (UAE), we retrospectively analyzed the case of patients with uterine
      leiomyomas who had undergone UAE. Methods. During the past 7 years, 25 patients
      with uterine leiomyomas had undergone UAE in our hospital. UAE was indicated in
      patients with menstrual disturbances such as hypermenorrhea or dysmenorrhea. The
      outcomes of this procedure for uterine leiomyomas were analyzed. Results.
      Improvement in the menstrual symptoms and/or reduction in the leiomyoma size
      after UAE were observed in 24 patients (96.0%). There was mean 67.9% reduction in
      the volume of leiomyomas at six months after UAE (P < 0.05). However, the
      symptoms recurred after UAE in 6 patients (24.0%), with multiple or intramural
      leiomyomas larger than 7 cm, which necessitated additional procedures.
      Conclusion. The indications and limitations of the UAE should be considered
      because of its noneffectiveness and/or recurrence in over 20% of patients with
      uterine leiomyomas.

PMID- 22135683
TI  - Stem cells and nuclear reprogramming.

PMID- 22135682
TI  - The haematopoietic stem cell niche: new insights into the mechanisms regulating
      haematopoietic stem cell behaviour.
AB  - The concept of the haematopoietic stem cell (HSC) niche was formulated by
      Schofield in the 1970s, as a region within the bone marrow containing functional
      cell types that can maintain HSC potency throughout life. Since then, ongoing
      research has identified numerous cell types and a plethora of signals that not
      only maintain HSCs, but also dictate their behaviour with respect to homeostatic
      requirements and exogenous stresses. It has been proposed that there are
      endosteal and vascular niches within the bone marrow, which are thought to
      regulate different HSC populations. However, recent data depicts a more
      complicated picture, with functional crosstalk between cells in these two
      regions. In this review, recent research into the endosteal/vascular cell types
      and signals regulating HSC behaviour are considered, together with the
      possibility of a single subcompartmentalised niche.

PMID- 22135685
TI  - A tribute to Professor Seyyed Behrouz Mousavi, D.D.S, MSc, Endodontist.

PMID- 22135684
TI  - Generation and characterization of erythroid cells from human embryonic stem
      cells and induced pluripotent stem cells: an overview.
AB  - Because of the imbalance in the supply and demand of red blood cells (RBCs),
      especially for alloimmunized patients or patients with rare blood phenotypes,
      extensive research has been done to generate therapeutic quantities of mature
      RBCs from hematopoietic stem cells of various sources, such as bone marrow,
      peripheral blood, and cord blood. Since human embryonic stem cells (hESCs) and
      induced pluripotent stem cells (iPSCs) can be maintained indefinitely in vitro,
      they represent potentially inexhaustible sources of donor-free RBCs. In contrast
      to other ex vivo stem-cell-derived cellular therapeutics, tumorigenesis is not a
      concern, as RBCs can be irradiated without marked adverse effects on in vivo
      function. Here, we provide a comprehensive review of the recent publications
      relevant to the generation and characterization of hESC- and iPSC-derived
      erythroid cells and discuss challenges to be met before the eventual realization
      of clinical usage of these cells.

PMID- 22135687
TI  - Patient satisfaction analysis on service quality of dental health care based on
      empathy and responsiveness.
AB  - BACKGROUND: Transformation of health care is underway from sellers' market to
      consumers' market, where the satisfaction of the patients' need is a primary
      concern while defining the service quality. Hence, commitment to provide a high
      quality service and achieving patients' satisfaction becomes an important issue
      for dental health care provider. The aim of this research is to investigate the
      quality of dental health care service based on empathy and responsiveness
      aspects. METHODS: A total of 90 questionnaires were completed by the dental
      patients who came to dental polyclinic located in Government Hospital, West Java,
      Indonesia. The questionnaire was concerned on two dimensions of service quality
      model, i.e. empathy and responsiveness. The obtained data were analyzed using
      inferential statistics (t test) and also descriptive statistics with importance
      performance analysis. RESULTS: All the attributes tested by t test showed that
      perception and expectation differed significantly, except for responsiveness,
      i.e. ability of dental assistants in assisting the dentist (t test 0.505<t table
      1.987). The most important factor in evaluating patient satisfaction is the
      response given by administration staff related to long waiting time (t test
      5.377), followed by dental assistant's knowledge about the patient's need during
      treatment (t test 4.822) and explanation that was given by dentist (t test
      4.700). CONCLUSION: It can be inferred from IPA that priority should be given to
      dentist's communication and dental assistant's knowledge toward patient's needs
      to enhance the service quality.

PMID- 22135686
TI  - Strategies used to inhibit postoperative swelling following removal of impacted
      lower third molar.
AB  - Postoperative swelling following different surgical strategies is an area of
      great interest. The main part of literature on the topic deals with swelling
      after extraction of low impacted third molar. In this review, we have analyzed
      publications of the last 20 years with a pubmed search using the following key
      words: impacted third molar, swelling third molar, wisdom tooth, edema jaw,
      corticosteroids and extraction third molar, antibiotic prophylaxis and tooth
      extraction. Attention has often been focused on corticosteroid therapy
      administered by diverse routes (orally, IV, IM, topically) and at different time
      schedules (before or after surgery or both). This investigation revealed how the
      use of different molecules and dosages makes the obtained results hardly
      comparable. Similar conclusions can be drawn from studies aimed at evaluating the
      efficacy of antibiotic therapy administered either before or after surgery. A
      complete review has also to take into account different surgical strategies used
      including various flaps, no traumatic osteothomy, and primary or secondary
      closure. The use of pharmacological therapy and application of an ice pack is
      critical in the postoperative period and has always provided positive results.
      However, even if it is difficult to come to definite conclusions, due to the
      variability of the design of studies analyzed, the postoperative discomfort
      identified with edema, pain and trismus following wisdom tooth removal is
      influenced by various factors such as the difficulty of the surgical procedure
      involved, age and gender of the patient, and experience of the surgeon. The
      pharmacological therapy when performed with corticosteroids seems to improve
      control of the postoperative swelling related with this kind of surgeries.

PMID- 22135688
TI  - Does the presence of the Helicobacter pylori in the dental plaque associate with
      its gastric infection? A meta-analysis and systematic review.
AB  - BACKGROUND: There is a great deal of studies on the relationship between the
      existence of Helicobacter pylori (H. pylori) in oral cavity (dental plaque) and
      in stomach of patients, with conflicting results worldwide. The purpose of this
      study was to systematically review the existing litreature to assess if the
      dental plaque could be a source of gastric H. pylori infection and to explore the
      source of heterogeneity around it. METHODS: We searched all the papers published
      since 2000 on international (Medline, ISI, Embase) databases using standard
      keywords. Two researchers evaluated the articles with standard critical appraisal
      form independently and those articles with the quality acquired greater than 70%
      were included in the study. The combined results were calculated with weighted
      average and the source of hetrogeneity was tested by meta-regression (random)
      model. RESULTS: Finally, 23 studies were included (1861 patients). The prevalence
      of co-infection of gastric and dental plaque H. pylori was 49.7% (95% CI 16
      83.4%) and the percent of agreement between the dental plaque H. pylori status
      and the gastric H. pylori was estimated as 82%. Only one study has reported that
      dental treatment has a preventive effect on the recurrence of gastric H. pylori
      infection. CONCLUSION: Co-infection of gastric H. pylori and dental plaque is
      reported by half of the studies. However, there is not enough evidence for the
      efficacy of dental treatment on prevention of recurrent gastric H. pylori
      infection.

PMID- 22135689
TI  - The effect of acidulated phosphate fluoride incorporated phosphoric acid etchant
      on shear bond strength of orthodontic brackets.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of adding acidulated
      phosphate fluoride (APF) to phosphoric acid etchant on shear bond strength (SBS)
      and adhesive remnant index (ARI) of orthodontic brackets bonded to etched teeth.
      METHODS: In this in vitro experimental study, 40 human premolars were etched with
      37% phosphoric acid solution (Dentsply) blended with 0, 25%, 50%, and 75%
      fractions of 1.23% APF (Dentsply). The brackets (Mini Dyna Lock, 3M) were bonded
      (Transbond XT, 3M) and were subjected to 96 hours of 37 degrees C incubation and
      thermocycling procedures (2000 cycles, 5-55 degrees C, dwell time = 30 s). Then,
      they were debonded at 1-mm crosshead speed to measure the SBS. The ARI was
      estimated at 10* magnification. The data were analyzed using the tests one-way
      analysis of variance (ANOVA), Tukey, chi-square, one-sample t-test, and Spearman
      correlation. RESULTS: The SBS of the groups control, 25%, 50%, and 75% APF were
      11.90+/-2.72, 8.01+/-3.13, 5.40+/-2.51, and 3.27+/-2.01 MPa, respectively. Mean
      ARI scores of these groups were 2.4 (control), 4.3, 4.7, and 4.8, respectively.
      According to the Tukey's test, only the mean SBS of the second group (25%) was
      not different from the control group (P=0.091). CONCLUSION: Adding about 20-25%
      of 1.23% APF to the phosphoric acid etchant might considerably reduce the amount
      of residual adhesive, without compromising the SBS.

PMID- 22135690
TI  - Evaluation of knowledge and plaque scores in school children before and after
      health education.
AB  - BACKGROUND: Health education is a process of transmission of knowledge and skills
      necessary for improvement in quality of life. The purpose of the present study
      was to evaluate the oral hygiene related knowledge and plaque scores of 12-year
      old school children in Belgaum city before and after health education. METHODS:
      Three schools of Belgaum city were randomly selected and assigned into one of
      three health educational groups - group I (audiovisual aids), group II (chalk and
      blackboard) and group III (no health education). Oral health related knowledge
      and plaque scores were assessed in all the groups before and after health
      education. RESULTS: The mean knowledge score before intervention in group I was
      7.94, in group II was 7.86 and in group III was 7.74 (P=0.86). After
      intervention, the mean knowledge score was 14.42 in group I, 12.7 in group II and
      9.58 in group III (P<0.001). Plaque scores in the three groups were similar and
      statistically nonsignificant at baseline. After the oral health education, the
      mean plaque scores were 0.627 in group I, 0.8826 in group II and 1.0156 in group
      III. Within the group comparisons revealed a statistically improved oral hygiene
      with decreased plaque scores in all the three groups. CONCLUSION: Health
      education by audiovisual aids could be an effective preventive measure against
      plaque-related oral diseases.

PMID- 22135691
TI  - The use of aminoguanidine, a selective inducible nitric oxide synthase inhibitor,
      to evaluate the role of nitric oxide on periapical healing.
AB  - BACKGROUND: Nitric oxide (NO) is one of the many chemical mediators involved in
      inflammatory processes. In addition to periapical inflammation, NO can have a
      role in periapical healing. The purpose of this study was to evaluate the effect
      of aminoguanidine (AG) as a selective inhibitor of inducible nitric oxide
      synthase (iNOS) on the degree of healing response of periapical lesions of the
      canine teeth of cats. METHODS: In this interventional experimental study, the
      root canals of 48 cat canine teeth were infected with cat dental plaque and
      sealed. After induction of periapical lesions, root canal therapy (RCT) was
      performed. On the day of RCT phase, the cats were administered either AG
      (experimental group) or normal saline (control group), which was continued on a
      daily basis until the day of sacrifice. Four canine teeth in one cat served as
      negative and positive controls. The animals were sacrificed 6 weeks after RCT.
      The healing response of the periapical zones was analyzed histologically. The
      mean scores of healing for the two groups were compared using Mann-Whitney U
      test. RESULTS: The mean scores of healing for the AG group (2.45+/-0.508) were
      significantly higher than those of the control group (2+/-0.510) (P<0.05).
      CONCLUSION: The use of an iNOS selective inhibitor such as AG can accelerate the
      healing process in periapical lesions.

PMID- 22135692
TI  - Comparison between cone beam computed tomography and panoramic radiography in the
      assessment of the relationship between the mandibular canal and impacted class C
      mandibular third molars.
AB  - BACKGROUND: Preoperative radiographic evaluation of impacted third molars is
      essential to determine the proximity to the mandibular canal to minimize the risk
      of nerve injury. Our study aim was to evaluate the relationship between the
      mandibular canal and impacted mandibular third molars using cone beam computed
      tomography (CBCT) and to compare findings therein with panoramic radiographic
      signs. METHODS: CBCT images were taken from 29 patients having 43 Class C
      impacted mandibular third molars whose panoramic radiographs showed a close
      relationship between the mandibular canal and mandibular third molars. We
      evaluated their tomographs to determine the course of the canal, its proximity to
      the root, any narrowing of the canal, the presence of root grooving or hooks and
      the proximity of the root to the cortex. A Chi-square test was used for data
      analysis. RESULTS: The lingual course of the canal was the most frequently
      detected course in all panoramic findings. Contact of the tooth with the canal
      was observed in all cases in which panoramic signs of deviation of the canal and
      darkening of the roots were found. The frequency of observing the narrowing of
      the canal in CBCT as compared to seeing the presence or the absence of canal
      narrowing in panoramic radiographs was significantly different (P=0.01).
      CONCLUSION: CBCT provides more precise diagnostic information to determine the
      relationship of impacted third molars to the canal. Deviation of the canal and
      darkening of the roots in panoramic view can be highly valuable to predict the
      risk of nerve injury.

PMID- 22135693
TI  - Influence of smokeless tobacco on periodontal health status in local population
      of north India: A cross-sectional study.
AB  - BACKGROUND: Limited studies have been published so far, which revealed the
      association of different types of smokeless tobacco on various periodontal health
      indicators, including mobility and furcation, on North Indian population. The
      present study has been undertaken to evaluate the effects of commonly used
      smokeless tobacco forms on periodontal health in Lucknow, North India. METHODS:
      This cross-sectional study investigated the effect of commonly used smokeless
      tobacco on periodontal health in local population of Lucknow, for which 2045
      individuals were evaluated. Amongst them, 1069 individuals were found to be using
      some kind of tobacco; amongst the tobacco users, n=122 were smokers, n=657 were
      only using only smokeless tobacco and n=290 were using both smokeless tobacco as
      well as tobacco in smoking form. After completing the questionnaire, all the
      participants underwent clinical examination for the various clinical parameters.
      RESULTS: The impact of smokeless form of tobacco use was significantly higher on
      all the periodontal health indicators, viz., plaque index, gingival index,
      calculus, clinical attachment loss, gingival recession, mobility, furcation,
      lesion, and probing pocket depth. Both duration and frequency of smokeless
      tobacco use significantly affected the periodontal health. CONCLUSION: The
      periodontal health of the general population in the region required immediate
      attention as majority of subjects irrespective of their habit status had onset of
      clinical attachment loss and gingival recession, more so amongst the smokeless
      tobacco users than smoking form of tobacco as well as than from non-tobacco
      users.

PMID- 22135694
TI  - A simple method for reconstruction of severely damaged primary anterior teeth.
AB  - Restoration of severely decayed primary anterior teeth is often considered as a
      special challenge by pedodontists. This case report presents a 5-year-old boy
      with severely damaged maxillary right canine. Subsequent to root canal treatment,
      a reversed (upside-down) metal post was put into the canal and composite build-up
      was performed. This new method offers a simple, practical and effective procedure
      for reconstruction of severely decayed primary anterior teeth, which re
      establishes function and esthetics for time the tooth should be present and
      functional in the child's mouth.

PMID- 22135695
TI  - Adenomatoid hyperplasia of lower lip.
AB  - Adenomatoid hyperplasia (AH) is an uncommon, non-neoplastic swelling on the
      palate caused due to hyperplasia of the mucinous acini. The lesion clinically
      presents as a sessile tumor-like nodule resembling pleomorphic adenoma.
      Histopathologic findings include lobules of enlarged mucinous acini which are
      filled with secretory granules. The nuclei are squeezed to the basal portions,
      associated with focal inflammation and ductal dilatation, and a history of trauma
      is often elicited. Here, we report a rare case of AH of the lower lip in a 20
      year-old male patient, which mimics a mucous retention cyst or mucocele.

PMID- 22135696
TI  - Facial talon in mandibular incisor: An unusual occurrence.
AB  - Talon cusp, also known as an eagle's talon, is a dental anomaly that occurs on
      the lingual aspect of teeth commonly, but occurrence on the facial aspect has
      rarely been reported. It is an extra cusp on an anterior tooth, which arises as a
      result of evagination on the surface of a crown before calcification has
      occurred. The incidence of talon cusp on lingual side is less than 6% and is even
      lesser on the facial aspect. Commonly involved teeth are maxillary incisors,
      usually unilateral but in some instances bilateral. The classical radiographical
      feature of talon cusp is double teeth appearance. The anomaly has been reported
      to be unusual in the mandibular dentition and extremely rare on the facial
      aspect. We report one such extremely rare case of facial talon cusp in mandibular
      central incisor.

PMID- 22135697
TI  - PEDIATRIC MENTAL HEALTH PROBLEMS AND ASSOCIATED BURDEN ON FAMILIES.
AB  - Approximately 20% of children in the United States have mental health problems.
      The factors associated with childhood mental health problems and the associated
      burdens on families are not well understood. Therefore, our goals were to profile
      mental health problems in children to identify disparities, and to quantify and
      identify correlates of family burden. We used the National Survey of Children's
      Health, 2003 (N=85,116 children aged 3-17 years) for this analysis. The
      prevalence, unadjusted and adjusted odds ratios of mental health problems and
      family burden were calculated for children by child-, family- and health systems-
      level characteristics. The prevalence of mental health problems among children
      aged 3-17 years was 18%. The odds of mental health problems were higher for boys,
      older children, children living in or near relative poverty, those covered by
      public insurance, children of mothers with fair or poor mental health, children
      living in homes without two parents, children without a personal doctor or nurse,
      and children with unmet health care needs. Among families with children with
      mental health problems, 28% reported family burden. Correlates of family burden
      included White race, severity, older age, higher income, non-two parent family
      structure, and having a mother with mental health problems. In conclusion,
      childhood mental health problems are common and disproportionally affect children
      with fewer family and health care resources. Families frequently report burden,
      especially if the mental health problem is moderate to severe, but the correlates
      of family burden are not the same correlates associated with mental health
      problems. Understanding those highest at risk for mental health problems and
      family burden will help assist clinicians and policy makers to ensure appropriate
      support systems for children and families.

PMID- 22135699
TI  - Transition from self-supported to supported living: Older people's experiences.
AB  - To become dependent on professional support to accomplish the daily activities of
      life can be considered a turning point, involving a range of challenging changes
      in life. The purpose of the study was to describe the experiences of older home
      dwelling individuals in transition from self-supported to supported living from a
      lifeworld perspective. Five women and five men were interviewed, and a
      descriptive phenomenological design was used. The findings showed that an
      attitude of acceptance was an essential characteristic for this group. An
      attitude of acceptance comprised: flexibility and tolerance, recognition and
      hopes, and valuation of self and situation. Finding themselves in a situation
      they had to submit to, they took an attitude of acceptance. An attitude of
      acceptance implied acknowledgement of the situation as well as positivity and
      desires to manage. This attitude may represent a significant potential for
      improvement. Awareness of this is crucial to support older individuals in a
      healthy way through the transition process. An attitude of acceptance, however,
      also implied an acceptance of discontinuity in their lives, renunciations, and
      denigration of own needs. But this aspect of the acceptance was trivialized by
      the participants and not equally obvious. Insight into this complexity is vital
      to avoid ignorance of older individuals' vulnerability in the transition process.

PMID- 22135698
TI  - Meta-Review of Metanalytic Studies with Repetitive Transcranial Magnetic
      Stimulation (rTMS) for the Treatment of Major Depression.
AB  - BACKGROUND: Major Depression (MD) and treatment-resistant depression (TRD) are
      worldwide leading causes of disability and therapeutic strategies for these
      impairing and prevalent conditions include pharmacological augmentation
      strategies and brain stimulation techniques. In this perspective, repetitive
      transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation
      technique with a favorable profile of tolerability which, despite being recently
      approved by the Food and Drug Administration (FDA) for the treatment of patients
      with medication-refractory unipolar depression, still raises some doubts about
      most effective parameters of stimulation. METHODS: A literature search was
      performed using PubMed for the years 2001 through February 2011 in order to
      review meta-analytic studies assessing efficacy and safety issues for rTMS in
      depressive disorders. Fifteen meta-analyses were identified and critically
      discussed in order to provide an updated and comprehensive overview of the topic
      with specific emphasis on potentially optimal parameters of stimulation. RESULTS:
      First meta-analyses on the efficacy of rTMS for the treatment of MD and TRD have
      shown mixed results. On the other hand, more recent meta-analytic studies seem to
      support the antidepressant efficacy of the technique to a greater extent, also in
      light of longer periods of stimulation (e.g. > 2 weeks). CONCLUSION: rTMS seems
      to be an effective and safe brain stimulation technique for the treatment of
      medication refractory depression. Nevertheless, further studies are needed to
      better define specific stimulation-related issues, such as duration of treatment
      as well as durability of effects and predictors of response.

PMID- 22135700
TI  - Closure of an open wound associated with bisphosphonate-related osteonecrosis of
      the jaw in a breast cancer patient.
AB  - BACKGROUND AND OBJECTIVE: Many clinicians will not treat patients presenting with
      bisphosphonate-related osteonecrosis of the jaw following long-term use of
      bisphosphonates because of the lack of predictable outcomes.   MATERICAL AND
      METHODS: The patient presented with pain from a nonhealing lesion in the
      posterior maxilla following extraction of the maxillary right third molar. The
      lesion had not responded to any conventional dental treatment. The patient had
      suffered from breast cancer, and her treatment included several years of therapy
      with Zometa (zoledronic acid), a bisphosphonate. RESULTS: The patient stopped
      taking Zometa and commenced rinsing with phosphate buffer-stabilized 0.1%
      chlorine dioxide-containing mouthwash. After 5 months, changes in the morphology
      of the lesion were noted and the soft tissue had closed over the open wound.
      CONCLUSION: Cessation of bisphosphonate therapy and usage of a phosphate buffer
      stabilized 0.1% chlorine dioxide-containing mouthwash lessened the patient's pain
      and resulted in closure of the soft tissue lesion.

PMID- 22135701
TI  - HLA-DQB1 Haplotypes and their Relation to Oral Signs Linked to Celiac Disease
      Diagnosis.
AB  - OBJECTIVES: Celiac disease (CD) is an autoimmune disorder that can be divided
      into typical and atypical forms. Atypical forms can show extraintestinal
      manifestations among which oral signs are very frequent. Considering that the
      pathogenesis of CD is related to a positivity to specific HLA-DQB1 haplotypes, we
      tested whether the presence of the HLA-DQB1*02 allele could be a hypothetical
      cause of the development of oral manifestations. SUBJECTS AND METHODS: For this
      study was been examined the oral condition of 98 Sardinian patients, all affected
      by CD and all on a gluten-free diet for at least 1 year. Then was been determined
      each patient's HLA-DQB1 haplotype and compared these results with clinical
      information. RESULTS: The statistical analysis evidenced that the absence of the
      HLA-DQB1*02 allele predisposes to oral manifestations such as dental enamel
      defects (DED) and recurrent aphthous stomatitis (RAS) (Pvalue=5.98x10(-05), OR =
      0.23, CI: (0.10 - 0.45) per each copy of the HLA allele). CONCLUSIONS: These
      results showed that the presence of the HLA-DQB1*02 allele influences the
      development of oral signs in a dose-dependent manner and also how the HLA
      haplotype connected to oral signs could have a fundamental role for the diagnosis
      of atypical forms of CD.

PMID- 22135702
TI  - Mononuclear Phagocytes in Rheumatoid Arthritis Patients and their Relatives -
      Family Similarity.
AB  - The aim of this work was to study the peripheral blood monocyte functions in
      patients with advanced RA and their predisposed to RA relatives in comparison
      with those in women, not hereditary tainted with autoimmune diseases (donors). In
      groups comprising 24 RA patients, 24 relatives, and 24 donors the following
      monocyte functions were assessed: engulfment and digestion (radioisotope method);
      release of lysosomal glucuronidase in response to opsonized zymosan (fluorescent
      method); reactive oxygen species (ROS) generation (chemiluminescence), and serum
      levels of proinflammatory cytokines (ELISA). The monocyte specific feature in
      patients and their relatives is chiefly extracellular digestion due to the
      delayed engulfment. The digestive activity, probably inhibited in relatives, is
      increased in advanced RA. ROS generation by the cells and serum levels of TNF
      alpha and IL-1-beta are abundant both in the patients and their relatives. High
      levels of pro-inflammatory cytokines, presumably, of monocyte origin, and
      increased levels of stimulated ROS generation may be due to the priming and
      prolonged activation of monocytes in relatives. CONCLUSION: We show for the first
      time that the functioning of circulating mononuclear phagocytes in the assumed to
      be healthy predisposed to RA individuals differs from that in the healthy people
      not hereditary tainted with autoimmune diseases and in general resembles the
      functioning of the cells in the patients with advanced RA.

PMID- 22135703
TI  - Telehealth as a means of health care delivery for physical therapist practice.

PMID- 22135704
TI  - Muscle atrophy and functional deficits of knee extensors and flexors in people
      with chronic stroke.
AB  - BACKGROUND: Further clarification is needed with regard to the degree of atrophy
      in individual muscle groups and its possible relationship to joint torque deficit
      poststroke. OBJECTIVE: The purpose of this study was to investigate quadriceps
      and hamstring muscle volume and strength deficits of the knee extensors and
      flexors in people with chronic hemiparesis compared with a control group. DESIGN:
      This was a cross-sectional study. METHODS: Thirteen individuals with hemiparesis
      due to chronic stroke (hemiparetic group) and 13 individuals who were healthy
      (control group) participated in this study. Motor function, quadriceps and
      hamstring muscle volume, and maximal concentric and eccentric contractions of the
      knee extensors and flexors were assessed. RESULTS: Only the quadriceps muscle of
      the paretic limb showed reduced muscle volume (24%) compared with the
      contralateral (nonparetic) limb. There were no differences in muscle volume
      between the hemiparetic and control groups. The peak torque of the paretic-limb
      knee extensors and flexors was reduced in both contraction modes and velocities
      compared with the nonparetic limb (36%-67%) and with the control group (49%-75%).
      The nonparetic limb also showed decreased extensor and flexor peak torque
      compared with the control group (17%-23%). Power showed similar deficits in
      strength (12%-78%). There were significant correlations between motor function
      and strength deficits (.54-.67). LIMITATIONS: Magnetic resonance imaging coil
      length did not allow measurement of the proximal region of the thigh.
      CONCLUSIONS: There were different responses between quadriceps and hamstring
      muscle volumes in the paretic limb that had quadriceps muscle atrophy only.
      However, both paretic and nonparetic limbs showed knee extensor and flexor torque
      and power reduction.

PMID- 22135705
TI  - Effect of time ratio of heat to cold on brachial artery blood velocity during
      contrast baths.
AB  - BACKGROUND: Contrast baths have been adopted widely in clinics. However, the time
      ratio of heat to cold modalities has not been well established. OBJECTIVE: The
      purpose of this study was to explore the effect of time ratio on brachial artery
      mean blood velocity (aMBV) and determine the optimal duration in the second
      heating phase. DESIGN: This was a within-participant, repeated-measures,
      experimental study. METHODS: Thirty-four young volunteers who were healthy were
      recruited. Each participant performed 2 kinds of contrast baths within 2 separate
      sessions. In the first trial with a fixed time ratio, participants immersed their
      left hands in a 40 degrees C hot bath for 3 minutes and then in an 18 degrees C
      cold bath for 1 minute. This procedure was repeated 3 times. In the second trial,
      after the initial 3-minute hot bath and 1-minute cold bath, a 10-minute 40
      degrees C hot bath immersion was adopted as the second cycle. A color Doppler
      ultrasound scanner was used to measure aMBV, which was used to calculate the
      percentage of change related to the baseline (aMBV%) and the fluctuation in the
      heating phases (DeltaaMBV%). RESULTS: In the first trial, compared with the first
      heating phase, the DeltaaMBV% was significantly lower by 57% and by 46% in the
      second and third heating phases, respectively. In the second trial, the
      DeltaaMBV% beyond the 7th minute did not reach a significantly lower level.
      LIMITATIONS: The results cannot be generalized to elderly individuals or patients
      with medical conditions. CONCLUSION: A longer duration in the second heating
      phase during contrast baths was required to produce a sufficient fluctuation in
      blood flow.

PMID- 22135706
TI  - Brazilian validation of the Alberta Infant Motor Scale.
AB  - BACKGROUND: The Alberta Infant Motor Scale (AIMS) is a well-known motor
      assessment tool used to identify potential delays in infants' motor development.
      Although Brazilian researchers and practitioners have used the AIMS in
      laboratories and clinical settings, its translation to Portuguese and validation
      for the Brazilian population is yet to be investigated. OBJECTIVE: This study
      aimed to translate and validate all AIMS items with respect to internal
      consistency and content, criterion, and construct validity. DESIGN: A cross
      sectional and longitudinal design was used. METHODS: A cross-cultural translation
      was used to generate a Brazilian-Portuguese version of the AIMS. In addition, a
      validation process was conducted involving 22 professionals and 766 Brazilian
      infants (aged 0-18 months). RESULTS: The results demonstrated language clarity
      and internal consistency for the motor criteria (motor development score,
      alpha=.90; prone, alpha=.85; supine, alpha=.92; sitting, alpha=.84; and standing,
      alpha=.86). The analysis also revealed high discriminative power to identify
      typical and atypical development (motor development score, P<.001; percentile,
      P=.04; classification criterion, chi(2)=6.03; P=.05). Temporal stability (P=.07)
      (rho=.85, P<.001) was observed, and predictive power (P<.001) was limited to the
      group of infants aged from 3 months to 9 months. LIMITATIONS: Limited predictive
      validity was observed, which may have been due to the restricted time that the
      groups were followed longitudinally. CONCLUSIONS: In sum, the translated version
      of AIMS presented adequate validity and reliability.

PMID- 22135707
TI  - Defining, agreeing on, and testing an international physical therapy core data
      set: results of a feasibility study involving seven countries.
AB  - BACKGROUND: To date, there has been no attempt to describe or compare physical
      therapy as practiced globally, nor any evidence that an international data set
      exists to support this effort. It is known that research evidence can be used in
      strategic and tactical ways, especially within the highly politicized context of
      the policy arena. The International Private Practitioners Association recognized
      the potential value a global evidence base could have in influencing policy and
      supporting professional development in a number of countries, yet it lacked a
      mechanism to achieve these aims. OBJECTIVES: The purposes of this study were: (1)
      to identify and test an international data set, definitions, and means of data
      collection and (2) to establish views in relation to the value of international
      collaborations. DESIGN: A mixed, prospective design was used in the study.
      METHOD: Phase 1 (2006-2007) involved the development of a data set, definitions,
      and Web-based and paper-based data collection options involving 98 physical
      therapists from 68 physical therapy practices in 7 countries. Phase 2 (2008-2009)
      involved testing of the data set in 34 practices involving 3,195 patient episodes
      and included physical therapist feedback of experience, local relevance of the
      data set, and value of international collaborations. RESULTS: Testing confirmed
      the relevance and reliability of the data set and definitions and a preference
      for Web-based data collection (74.0%). Physical therapist feedback supported
      these findings. Most respondents (60.0%-100.0%) reported the value of further
      international collaborations for their profession nationally or internationally.
      LIMITATIONS: Although a true international collaboration, the limited sample size
      should be recognized. CONCLUSIONS: It is possible to develop an agreed-upon
      international data set and means of data collection. Testing appears to support
      its acceptability and relevance for use in practice. Participants highly valued
      the opportunity to undertake international collaborations that may benefit their
      profession nationally and internationally. Further testing and use of the data
      set are advocated before final validation is sought.

PMID- 22135708
TI  - Executive function and type 2 diabetes: putting the pieces together.
AB  - The devastating impact of type 2 diabetes mellitus (DM) on vascular, renal,
      retinal, and peripheral nerve functions has been well documented. However, there
      is also evidence that older adults with this disease exhibit impairments in the
      planning, coordinating, sequencing, and monitoring of cognitive operations,
      collectively known as executive function. Although poorly understood,
      disturbances in executive function, particularly within the dimension of time
      sharing, may contribute to the gait abnormalities and increased risk for falls,
      functional impairments, and disabilities associated with type 2 DM. However, the
      relationships between executive function and functional abilities remain poorly
      understood in this population. Current neuropsychological research regarding the
      concept of executive function is presented here as a framework upon which to
      examine the integrity of this critical cognitive entity in adults with type 2 DM.
      The pathophysiological mechanisms thought to underlie diabetes-related executive
      dysfunction are explored, and the possible contributions of executive deficits to
      impairments in gait and function observed in older people with type 2 DM are
      summarized. Finally, a brief discussion of dual-task assessment and intervention
      strategies that may facilitate the care and rehabilitation of the growing
      population of patients with type 2 DM is provided.

PMID- 22135709
TI  - Understanding falls in multiple sclerosis: association of mobility status,
      concerns about falling, and accumulated impairments.
AB  - BACKGROUND: Falls in people with multiple sclerosis (MS) are a serious health
      concern, and the percentage of people who restrict their activity because of
      concerns about falling (CAF) is not known. Mobility function and accumulated
      impairments are associated with fall risk in older adults but not in people with
      stroke and have not been studied in people with MS. OBJECTIVE: The purposes of
      this study were: (1) to estimate the percentage of people who have MS and report
      falling, CAF, and activity restrictions related to CAF; (2) to examine
      associations of these factors with fall status; and (3) to explore associations
      of fall status with mobility function and number of accumulated impairments.
      DESIGN: A cross-sectional survey was conducted. METHODS: A total of 575 community
      dwelling people with MS provided information about sociodemographics, falls, CAF,
      activity restrictions related to CAF, mobility function, and accumulated
      impairments. Chi-square statistics were used to explore associations among these
      factors. RESULTS: In all participants, about 62% reported CAF and about 67%
      reported activity restrictions related to CAF. In participants who did not
      experience falls, 25.9% reported CAF and 27.7% reported activity restrictions
      related to CAF. Mobility function was associated with fall status; participants
      reporting moderate mobility restrictions reported the highest percentage of
      falls, and participants who were nonwalkers (ie, had severely limited self
      mobility) reported the lowest percentage. Falls were associated with accumulated
      impairments; the participants who reported the highest percentage of 2 or more
      falls were those with 10 impairments. LIMITATIONS: This cross-sectional study
      relied on self-reported falls, mobility, and impairment status, which were not
      objectively verified. CONCLUSIONS: Both CAF and activity restrictions related to
      CAF were common in people with MS and were reported by people who experienced
      falls and those who did not. The association of fall status with mobility
      function did not appear to be linear. Fall risk increased with declining mobility
      function; however, at a certain threshold, further declines in mobility function
      were associated with fewer falls, possibly because of reduced fall risk exposure.

PMID- 22135710
TI  - Validation of the Revised Physical Therapist Clinical Performance Instrument (PT
      CPI): Version 2006.
AB  - BACKGROUND: Based on changes in core physical therapy documents and problems with
      the earlier version, the Physical Therapist Clinical Performance Instrument (PT
      CPI): Version 1997 was revised to create the PT CPI: Version 2006. OBJECTIVE: The
      purpose of this study was to validate the PT CPI: Version 2006 for use with
      physical therapist students as a measure of clinical performance. DESIGN: This
      was a combined cross-sectional and prospective study. METHODS: A convenience
      sample of physical therapist students from the United States and Canada
      participated in this study. The PT CPI: Version 2006 was used to collect CPI item
      level data from the clinical instructor about student performance at midterm and
      final evaluation periods in the clinical internship. Midterm evaluation data were
      collected from 196 students, and final evaluation data were collected from 171
      students. The students who participated in the study had a mean age of 24.8 years
      (SD=2.3, range=21-41). Sixty-seven percent of the participants were from programs
      in the United States, and 33% were from Canada. RESULTS: The PT CPI: Version 2006
      demonstrated good internal consistency, and factor analysis with varimax rotation
      produced a 3-factor solution explaining 94% of the variance. Construct validity
      was supported by differences in CPI item scores between students on early
      compared with final clinical experiences. Validity also was supported by
      significant score changes from midterm to final evaluations for students on both
      early and final internships and by fair to moderate correlations between prior
      clinical experience and remaining course work. LIMITATIONS: This study did not
      examine rater reliability. CONCLUSION: The results support the PT CPI: Version
      2006 as a valid measure of physical therapist student clinical performance.

PMID- 22135711
TI  - Effect of peroneal electrical stimulation versus an ankle-foot orthosis on
      obstacle avoidance ability in people with stroke-related foot drop.
AB  - BACKGROUND: Walking ability of people with foot drop in the chronic phase after
      stroke is better with functional electrical stimulation (FES) of the peroneal
      nerve than without an orthotic device. However, the literature is not conclusive
      on whether peroneal FES also is better than an ankle-foot orthosis (AFO) in this
      regard. OBJECTIVE: This study aimed to identify potential benefits of peroneal
      FES over an AFO with respect to the ability to negotiate a sudden obstacle.
      DESIGN: The study design was a within-subject comparison between FES and AFO
      using repeated measures. METHODS: Twenty-four community-dwelling people with
      stroke (mean age=52.6 years, SD=12.7) who regularly used a polypropylene AFO were
      fitted with a transcutaneous FES device. The participants' obstacle avoidance
      ability was tested after 2 and 8 weeks. They had to avoid 30 obstacles that were
      suddenly dropped on a treadmill in front of the affected leg while walking with
      either FES or an AFO. The obstacle avoidance success rates were determined.
      RESULTS: Success rates were higher with FES than with an AFO, especially after
      adjustment for individual leg muscle strength. Participants with relatively low
      muscle strength (Motricity Index score <64) were most likely to benefit from FES
      regarding obstacle avoidance ability. LIMITATION: Further work is needed to
      determine whether the results may be generalized to other groups of people with
      stroke. CONCLUSIONS: Peroneal FES seems to be superior to an AFO with regard to
      obstacle avoidance ability in community-dwelling people with stroke. The observed
      gains in obstacle avoidance ability appear to be clinically most relevant in the
      people with relatively low leg muscle strength.

PMID- 22135712
TI  - Effect of motor control exercises versus graded activity in patients with chronic
      nonspecific low back pain: a randomized controlled trial.
AB  - BACKGROUND: Motor control exercises to improve control and coordination of trunk
      muscles and graded activity under the principles of cognitive-behavioral therapy
      are 2 commonly used exercise therapies, yet there is little evidence to support
      the use of one intervention over the other. OBJECTIVE: The objective of this
      study was to compare the effectiveness of motor control exercises and graded
      activity for patients with chronic nonspecific low back pain. DESIGN: This study
      was a prospectively registered randomized controlled trial with outcome
      assessment and statistical analyses conducted blind to group. SETTING: The study
      was conducted in primary care settings. PATIENTS: The participants were 172
      patients with chronic (>12 weeks) nonspecific low back pain. INTERVENTIONS:
      Patients were randomly assigned to receive either motor control exercises or
      graded activity. There was no attempt to subclassify patients to match them to a
      treatment. Patients in both groups received 14 sessions of individualized,
      supervised exercise therapy. MEASUREMENTS: Primary outcomes were average pain
      over the previous week (numeric rating scale) and function (Patient-Specific
      Functional Scale); secondary outcomes were disability (24-item Roland-Morris
      Disability Questionnaire), global impression of change (Global Perceived Effect
      Scale), and quality of life (36-Item Short-Form Health Survey questionnaire [SF
      36]). Outcome measures were collected at baseline and at 2, 6, and 12 months
      after intervention. RESULTS: A linear mixed models analysis showed that there
      were no significant differences between treatment groups at any of the time
      points for any of the outcomes studied. For example, the effect for pain at 2
      months was 0.0 (-0.7 to 0.8). LIMITATIONS: Clinicians could not be blinded to the
      interventions. CONCLUSION: results of this study suggest that motor control
      exercises and graded activity have similar effects for patients with chronic
      nonspecific low back pain.

PMID- 22135713
TI  - Prognosis of surgical treatment for degenerative lumbar spinal stenosis: a
      prospective cohort study of clinical outcomes and health-related quality of life
      across gender and age groups.
AB  - Degenerative lumbar spinal stenosis is a common condition and the most usual
      indication for spinal surgery in adult patients. The main objective of this study
      was to investigate clinical outcomes, health-related quality of life (HRQoL) and
      satisfaction among patients with a diagnosed lumbar spinal stenosis who were
      surgically treated, and whether these outcomes differed according to gender and
      age. Surgery was performed on 100 patients with clinical and radiological defined
      lumbar spinal stenosis. All patients completed questionnaires twice before
      surgery and at 6 weeks, 12 weeks, and 1 year postoperatively. Main outcomes were
      symptoms, physical function and patient satisfaction assessed by the Swiss Spinal
      Stenosis Questionnaire and HRQoL by the Short Form 36 health survey (SF36). There
      were large improvements in all clinical outcomes and in the physical subscales of
      the SF36. A marked reduction of average 32.3% was seen in symptoms already at 6
      weeks follow-up. Physical function had improved with an average of 29.8% at 1
      year follow-up. There was no statistical significant effect of age and gender on
      symptoms and physical function. Patients more than 65 years were significantly
      less satisfied at the 1-year follow-up as compared to the younger patients
      (p=0.012). This study showed that the majority of patients improved significantly
      in symptoms, physical function and physical HRQoL after surgery for degenerative
      lumbar spinal stenosis, regardless of age and gender. Age showed to be closely
      connected to satisfaction.

PMID- 22135714
TI  - Discord of biological and psychological measures in a group of depressed african
      american and white cancer patients.
AB  - OBJECTIVE: This study examined racial differences in the self-report of
      depressive symptoms by reference to biological states. METHODS: The study used a
      convenience sample of 20 depressed cancer patients (CES-D >=16) (15 African
      Americans and 5 Whites). Subjects completed depression assessment on a battery of
      psychological measures and provided blood and saliva samples. Laboratory tests
      were performed on biomarkers (serotonin, cortisol and IL-6). T-test was computed
      to examine racial differences on biological and psychological measures. RESULTS:
      Depressed Whites had a significantly higher cortisol level than depressed African
      Americans, but no significant group difference was found on any self-reported
      psychological measures of depression. There was a trend that African Americans
      reported fewer depressive symptoms on psychological measures but exceeded Whites
      on the domain of somatization; however, such group differences did not approach
      statistic significance in this small sample. CONCLUSION: African Americans did
      not appear to underreport depression in consideration of their biological states,
      but had a tendency to report more somatic symptoms than Whites; this may be
      attributable to non-depression diseases or reporting behavior rather than somatic
      sensitivity. African Americans exhibited more mistrust in the health care system,
      which could affect the self-report of depression. There is a discord between
      biological and psychological measures of depression. Biomarkers prove to be
      useful for evaluating racial difference in the self-report of depression. 
      IMPLICATION FOR NURSING:  Nurses should be cautious of somatic complaints when
      assessing African American cancer patient's depression. Establishing trust is
      essential for an accurate assessment of depression in African American cancer
      patients.

PMID- 22135715
TI  - Information sharing and case conference among the multidisciplinary team improve
      patients' perceptions of care.
AB  - BACKGROUND: As the advent of genomic technology accelerates personalized medicine
      and complex care, multidisciplinary care is essential for management of breast
      cancer. OBJECTIVES: To assess whether healthcare delivery systems are related to
      patients' perceptions of care in breast cancer treatment institutions. METHODS:
      We conducted a cross-sectional nationwide study of breast cancer treatment
      institutions approved by the Japanese Breast Cancer Society in Japan. From 128 of
      the 457 institutions, 1,206 patients were included in the analysis. Each patient
      completed a questionnaire regarding perceptions of care that consisted of a
      multidisciplinary care subscale and a patient-centered care subscale. RESULTS:
      Multiple regression analysis revealed that the multidisciplinary care subscale
      was significantly related to implementation of patient-based medical record
      system that was paper-based (p<0.05). The results of the secondary analysis
      showed a significant relationship between the interdepartmental medical record
      system and the patient's perception of multidisciplinary care (p<0.05) and
      patient-centered care (p<0.05). When a multidisciplinary case conference took
      place regularly or multidisciplinary viewpoints were incorporated into the
      conference records, the conference had a significantly higher correlation with
      both subscales (p<0.001). CONCLUSIONS: Integrated patient-based information and
      regular multidisciplinary case conferences that include records of viewpoints
      from different professionals improve patients' perceptions of comprehensive
      breast cancer care.

PMID- 22135716
TI  - Germany's First Young Carers Project's Impact on the Children: Relieving the
      Entire Family. A Qualitative Evaluation.
AB  - BACKGROUND: In 2009, the first German young carers project "SupaKids" was
      implemented in a large German city. The project's concept was mainly based on
      findings of a prior Grounded Theory study, and the concept's aim was to focus on
      supporting enrolled families (especially the children) in order to prevent
      negative effects. Quantitative as well as qualitative data have been assessed for
      the project's evaluation. In this paper, first results on the mainly qualitative
      evaluation concerning the project's impact are presented. RESULTS: The project
      has an impact on the entire family. Both parents and children perceive the
      project as a kind of shelter, where they a) are allowed to be as they are, b)
      don't have to explain themselves, c) meet others in similar situations, d) may
      deposit their sorrows, e) have a first port of call for any problem, f)
      experience a hiatus from the domestic situation, and g) find friends and peers.
      All enrolled families value this shelter as a copious relief. CONCLUSIONS: The
      project's concept has delivered an optimal performance in practice: the family
      orientation seems to be appropriate, the concept's modules seem to be all
      embracing, and the modular body of the concept has been confirmed. The project
      relieves the entire family. TRIAL REGISTRATION NUMBER: NCT00734942.

PMID- 22135717
TI  - "Striving for a good life" - the management of rheumatoid arthritis as
      experienced by patients.
AB  - AIM: To generate a theoretical model how patients experience their management of
      rheumatoid arthritis (RA) in everyday life. METHOD: An explorative design with
      the grounded theory approach was used by interviewing 16 informants with RA.
      RESULTS: The generated theoretical model emerged in a core category- Striving for
      a good life with two categories; making use of personal resources and grasping
      for support from others, which formed the base of managing RA. When relating
      these categories together, four dimensions emerged which characterised patients'
      different ways of managing RA: mastering, relying, struggling and being resigned.
      DISCUSSION: The management of RA incorporated the use of personal resources and
      the grasping for support from others. Both self-management strategies and
      patients' need of support were highlighted as aspects that were of importance
      when managing RA. Patients' experiences of their need of support to manage RA
      give extended knowledge that is of importance for nurses and other healthcare
      providers. The relationship between patients and healthcare providers is always
      the key to a good encounter. Interventions to increase self-management in RA have
      to incorporate this knowledge when trying to increase patients' self-efficacy and
      with their experience of support.

PMID- 22135718
TI  - The challenge of coming to terms with the use of a new digital assistive device:
      a case study of two persons with mild dementia.
AB  - There is an increased interest in supporting persons with dementia with technical
      services in daily life. The aim of this case study was to explore the complex
      issues involved in the process from a user driven development to the acceptance
      and usage of a new digital assistive device for persons with mild dementia. Even
      though it was developed in a user driven process and personalized to meet their
      individual needs they rarely used it. To deepening the understanding of this
      disparity between actual usage and perceived usefulness, the participants were
      studied whilst performing daily life activities through participant observations
      and interviews. Their partners were interviewed two years after the first
      observations to clarify the change in needs over time. The results show that the
      participant needs encompassed occupation, safety, social interaction, and memory
      support together with the receipt of general support. The overriding requirement
      for both participants was a need to maintain their self-image. When the digital
      assistive device did not correspond with the participants' expectations or view
      of themselves, their interest in using it faded, since the digital assistive
      device failed to support their self-image. The acceptance of a digital assistive
      device by a person with dementia is a process that begins with identifying and
      personalizing the functions of the device according to individual needs, and then
      supporting the usage and the gradual integration of the device into daily life.
      During this process, the person's self-image must be taken into consideration and
      supported.

PMID- 22135719
TI  - Smaller regional gray matter volume in homeless african american cocaine
      dependent men: a preliminary report.
AB  - Models of addiction include abnormalities in parts of the brain involving
      executive function/inhibitory control. Although previous studies have reported
      evidence of structural abnormalities in cocaine-dependent individuals, none have
      specifically targeted the homeless. The present preliminary study investigated
      brain structure in such an understudied group, homeless, crack-cocaine-dependent
      African American men (n = 9), comparing it to that in healthy controls (n = 8).
      Structural data were analyzed using voxel based morphometry (VBM) and a regions
      of interest (ROI) analysis. Homeless cocaine-dependent individuals had smaller
      gray matter volume in dorsolateral prefrontal cortex, anterior cingulate, the
      cerebellum, insula, and superior temporal gyrus. Most of these areas subserve
      executive function or inhibitory control. These results are similar to those
      found in most previous studies of non-homeless cocaine-dependent individuals.
      Reduced gray matter in executive function/inhibitory control regions of the brain
      in cocaine-dependent individuals may be a preexisting risk factor for the
      development of addiction and/or a consequence of drug abuse.

PMID- 22135720
TI  - Clinicopathologic significance of putative stem cell markers, CD44 and nestin, in
      gastric adenocarcinoma.
AB  - Cancer stem cells (CSC) are unique subpopulations that have the capacity to drive
      malignant progression and mediate radio/chemoresistance. The role of nestin as a
      CSC marker in gastric adenocarcinoma is largely unknown. Our objective was to
      evaluate immunoexpression of CSC markers CD44 and nestin in gastric
      adenocarcinoma versus non-neoplastic gastric mucosae (NNGM) and correlate it with
      various clinicopathologic factors. Tissue microarray blocks from 174 cases of
      gastric adenocarcinoma and 41 samples of adjacent NNGM were assembled. Clinical
      data including patient's age and sex, tumor histologic subtype and grade, and
      disease stage were obtained. Expression of CD44 and nestin was assessed by
      immunohistochemistry. Expression of membranous CD44 (51%, 78/152) and cytoplasmic
      nestin (25%, 43/174) was significantly greater in gastric adenocarcinoma than in
      NNGM (P<0.001). A subset of cases (n=15) that co-expressed membranous CD44 and
      cytoplasmic nestin were significantly more frequent in Lauren intestinal
      histologic subtype than in diffuse subtype (P<0.05). Foci of intestinal
      metaplasia (n=6) showed either CD44 (3/6) or nestin (2/6) expression. This is the
      first study to report the clinicopathologic significance of nestin expression in
      gastric cancers, and to correlate the nestin expression with CD44, another stem
      cell marker. The study shows that nestin and CD44, are significantly expressed in
      a subset of gastric adenocarcinoma, particularly co-expression of nestin and CD44
      is significantly revealed in Lauren intestinal histologic subtype. Their
      expression is also increased in intestinal metaplasia, a premalignant lesion.
      These findings suggest that CSCs may have a pathogenetic role in the pathway of
      intestinal metaplasia-intestinal type gastric adenocarcinoma.

PMID- 22135721
TI  - beta-catenin expression in benign and malignant pleural disorders.
AB  - Benign and malignant pleural processes display a large and overlapping spectrum
      of morphological appearances, and can be difficult to distinguish,
      histologically, from each other. beta-catenin, a participant in the wingless-type
      (Wnt) transduction pathway, is involved in the pathogenesis of malignant
      mesothelioma and has received limited evaluation for its ability to serve as a
      diagnostic aid for distinguishing between individual pleural disorders. We
      performed immunohistochemistry for beta-catenin on 10 pleural malignant
      mesotheliomas, 10 examples of mesothelial hyperplasia and 18 cases of organizing
      pleuritis. Although differences were noted in staining intensity between the
      mesothelioma and mesothelial hyperplasia groups, extensiveness and cellular
      location were similar. Staining intensity (mean +/- s.d.) in mesotheliomas (2.00
      +/- 0.67) was significantly less intense than in mesothelial hyperplasia cases
      (3.00 +/- 0.00) (p=0.0005). Stromal cell staining was cytoplasmic in all cases,
      and endothelial cell staining was membranous, submembranous and cytoplasmic.
      Nuclear expression of beta-catenin was not observed in any of the cases studied.
      This lack of nuclear staining in the stromal cells of organizing pleuritis
      differs markedly from the previously reported high frequencies of nuclear beta
      catenin expression in other pleural spindle cell proliferations (desmoid tumors
      and solitary fibrous tumors). In summary, the current study adds to previous work
      indicating a role for beta-catenin in the genesis of pleural conditions including
      organizing pleuritis, mesothelial hyperplasia and malignant mesothelioma.
      Although IHC for beta-catenin does not appear to be conclusive for separating
      benign from malignant mesothelial proliferations, it may be valuable for
      assisting in the differential diagnosis of mesothelial and spindle cell
      proliferations in the pleura.

PMID- 22135722
TI  - Evaluation of a high avidity anti-dsDNA IgG enzyme-linked immunosorbent assay for
      the diagnosis of systemic lupus erythematosus.
AB  - The high avidity (HA) anti-dsDNA IgG ELISA is considered highly specific for the
      diagnosis of systemic lupus erythematosus (SLE). The main objective of this study
      was to determine the performance of this test with existing assays for detecting
      anti-dsDNA IgG antibodies as well as assess its analytical characteristics. For
      method comparison studies, we investigated the correlation between the HA ELISA
      with 8 other assays for the detection of dsDNA IgG antibodies namely; six anti
      dsDNA IgG ELISA, the Crithidia luciliae immunofluorescence test (CLIFT) and an in
      house developed Farr radioimmunoassay (RIA). Overall, 125 patient (100 ANA
      positive, 25 CLIFT-tested) and 100 healthy control samples were tested. The assay
      was also evaluated for imprecision, lot-to-lot consistency and the effect of
      interfering substances using commercial quality control materials based on the
      manufacturer's claims unless otherwise stated. Of the 100 ANA positive samples,
      18 were positive in the HA ELISA with significant levels of antibodies in the six
      ELISAs and CLIFT. The HA ELISA had a specificity of 100% with an overall
      agreement of 84% with the RIA. Intra - and inter-assay imprecision ranged from
      13.9-16.5% and the reproducibility between lots based on qualitative
      interpretation was 100%. Hemoglobin, bilirubin and lipemia showed variable
      interference with assay performance based on the manufacturer's claims and our in
      house protocol. Our data suggest that the HA ELISA although less sensitive than
      the other dsDNA IgG assays evaluated, is specific and predicts high levels of
      anti-dsDNA IgG antibodies.

PMID- 22135723
TI  - Immunohistochemical expressions of fatty acid synthase and phosphorylated c-Met
      in thyroid carcinomas of follicular origin.
AB  - Thyroid carcinoma is the most common endocrine malignancy and the first cause of
      death among endocrine cancers. Fatty acid synthase (FASN) and c-Met are
      overexpressed in many types of human cancers. Recent studies have suggested a
      functional interaction between FASN and c-Met. However, their roles in thyroid
      carcinomas have not been fully investigated. In this study, we evaluated the
      expressions of FASN and phosphorylated (p)-c-Met by using immunohistochemistry in
      thyroid carcinomas of follicular origin, from 32 patients. The adjacent non
      neoplastic thyroid tissue was also evaluated for comparison. Immunoreactive
      intensity and extensiveness were semi-quantified. The overexpression of FASN was
      observed in a subset of papillary thyroid carcinomas (PTC) including the
      classical type and tall cell, follicular, trabecular/insular and diffuse
      sclerosing variants, a subset of follicular thyroid carcinomas (FTC), and the PTC
      and FTC components in anaplastic thyroid carcinomas (ATC). No overexpression was
      observed in the ATCs per se and the columnar cell, solid, and cribriform variants
      of PTCs. All Hurthle cell variant FTCs and non-neoplastic Hurthle cells
      demonstrated positive staining for FASN while the non-neoplastic follicular cells
      without Hurthle cell change were negative. An association in overexpression
      between FASN and p-c-Met was observed in the majority of carcinomas as well as in
      the non-neoplastic Hurthle cells. In conclusion, overexpressions of FASN and p-c
      Met were observed in a subset of thyroid carcinomas of follicular origin, which
      may be of values for targeted therapy and predicting prognosis while the positive
      immunostaining for these immunomarkers may be nonspecific for Hurthle cell
      thyroid carcinomas.

PMID- 22135724
TI  - EPO improves the proliferation and inhibits apoptosis of trophoblast and decidual
      stromal cells through activating STAT-5 and inactivating p38 signal in human
      early pregnancy.
AB  - The erythropoietin (EPO) belongs to the family of angiogenic factors, which is
      regulated by Hypoxia-inducible factor- 1alpha (HIF-1alpha). As known, EPO are
      expressed in human villi and decidua, but the function is not clear. In this
      study, we investigated the expression and roles of HIF-1alpha, EPO and its
      receptor (EPOR) in the biological functions of trophoblast and decidual stromal
      cell (DSC) in human early pregnancy. The expression of EPO, EPOR and HIF-1alpha
      was evaluated in the villi and deciduas by RT-PCR and immunohistochemistry.
      Thereafter, we silenced HIF-1alpha expression in HTR-8/SVneo cell line and
      decidual stromal cells (DSCs). The effects of EPO on the proliferation and
      apoptosis of trophoblasts and DSCs, and activation of signal molecules were
      investigated by BrdU proliferation assay, flow cytometry and western blot,
      respectively. We have observed that the HIF-1alpha silence results in the lower
      expression of EPO in trophoblasts and DSCs. The anti-EPO neutralizing antibody
      can inactivate the phosphorylation of STAT5 and activate p38 of these cells in a
      dosage-dependent manner. Furthermore, the expressions of EPO, EPOR and HIF-1alpha
      in the villi and decidua from the unexplained miscarriage were significantly
      lower than that of the normal early pregnancy. This study suggests that HIF
      1alpha may regulate the expression of EPO, which plays a favorable regulatory
      role in the proliferation and survival of human first-trimester trophoblast cells
      and DSCs via inactivating p38 and activating STAT5 in an autocrine manner, while
      the inadequate EPO expression at maternal-fetal interface may lead to pregnancy
      wastage in humans.

PMID- 22135725
TI  - C-kit expression in human osteosarcoma and in vitro assays.
AB  - Biologic agents targeting oncogenes have encourage researchs trying to correlate
      the role of tyrosine kinase in the pathogenesis of tumours. Osteosarcoma is a
      high grade aggressive neoplasm with poor survival. Our aim was to investigate c
      kit immunoexpression, its prognostic relevance for patients with osteosarcoma,
      and the effect of imatinib mesylate (STI571) on proliferation and invasion of the
      human osteosarcoma cell line.A retrospective immunohistochemical study was
      performed on archival formalin-fixed paraffin-embedded specimens from 52 patients
      with high-grade primary osteosarcoma of extremities treated at the Pediatric
      Oncology Institute (IOP, GRAAC) and archived in the Department of Pathology,
      Federal University of Sao Paulo. Only pre-chemotherapy specimens were analyzed.
      Strongly stained cytoplasm and membrane cells were taken as positive. Human
      osteosarcoma cells from line MG-63 were incubated and the inhibitory effect of
      imatinib mesylate (STI571) on cell proliferation and invasion was studied. In 24
      cases (46.15%), c-kit was expressed by the cells and c-kit-positive tumors
      exhibited lower necrosis post-chemotherapy. No correlation was found between c
      kit expression and overall and disease-free survival. Imatinib mesylate decreased
      the rates of cell growth of osteosarcoma cells in low doses and invasion in high
      doses C-kit-positive tumors had worse response to chemotherapy and imatinib
      mesylate can play a role in blocking or decreasing the rate of growth of
      osteosarcoma cells, but not the invasive capacity of these neoplastic cells.
      These data suggested that imatinib mesylate could be a therapeutic target of
      strategies against osteosarcoma tumors. Further studies are necessary to confirm
      this indication.

PMID- 22135726
TI  - Intravascular large B-cell lymphoma: report of three cases and analysis of the
      mTOR pathway.
AB  - Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive and often
      fatal non-Hodgkin lymphoma characterized by preferential growth of malignant B
      cells within the lumina of small vessels. Rituximab plus anthracycline-based
      chemotherapy is the current standard regimen for IVLBCL, however it has minimal
      efficacy in relapsed or refractory diseases. Recent clinical trials have shown a
      significant anti-lymphoma activity of mammalian target of rapamycin (mTOR)
      inhibitors in relapsed and refractory diffuse large B-cell lymphoma (DLBCL);
      however, the activation status of the mTOR pathway and the therapeutic potential
      of mTOR inhibitors in IVLBCL have not yet been studied. Here we described the
      clinicopathological features of 3 cases of IVLBCL diagnosed at our institutions,
      and evaluated the activation status of the mTOR signaling in these tumors. Our
      results showed that the mTOR complex 2 pathway was selectively upregulated in
      IVLBCL, as evidenced by a predominant nuclear localization of the activated form
      of mTOR (p-mTOR at Ser2448) with concomitant overexpression of nuclear p-Akt
      (Ser473) and vascular endothelial growth factor (VEGF)-A in the lymphoma cells.
      These data suggest that overactivation of mTOR pathway may play a role in
      lymphomagenesis of IVLBCL and mTORC2 inhibitors may be beneficial in treating
      IVLBCL.

PMID- 22135727
TI  - Angiosarcoma of the mandibular gingiva.
AB  - Angiosarcoma of the oral cavity is extremely rare. A 77-year-old woman consulted
      to our hospital because of polypoid mass of the mandibular gingival. Physical
      examination showed polypoid reddish mass measuring 1.5 * 1.5 * 1 cm in the
      mandibular gingival posterior to the front tooth. Enucleation of the tumor was
      performed. Grossly, the tumor was not encapsulated. Histologically, the tumor
      consisted of atypical spindle with hyperchromatic nuclei with nucleoli. Mitotic
      figures were scattered. Vasoformative channels were present in some areas. The
      surgical margins were positive. Immunohistochemically, the tumor cells were
      positive for factor VIII-related antigen, CD31, CD34, vimentin, p53 protein, but
      negative for pancytokeratin (AE1/3 and CAM5.2), S100 protein, alpha-smooth muscle
      antigen, and desmin. The Ki-67 labeling was 60%. A pathological diagnosis of
      angiosarcoma was made. Radical operation is planned now.

PMID- 22135728
TI  - Papillary squamous cell carcinoma of the oral cavity with acantholytic and
      pseudovascular features.
AB  - Herein reported is a case of papillary squamous cell carcinoma (PSCC) in the oral
      cavity with features of koilocytosis, acantholysis and pseudovascular structure.
      A 73-year-old woman consulted to our hospital because of a tumor in the right
      mandibular gum. Physical examination revealed an exophytic papillary tumor of the
      right mandibular gum, and a biopsy was performed. The biopsy revealed squamous
      cell carcinoma. No metastases were found by various imaging techniques.
      Therefore, resection of the tumor and mandibular bone was performed. Grossly, the
      tumor was exophytic and papillary, and measured 2 * 2 * 1 cm. The mandibular bone
      was free from tumor invasion. Microscopically, the tumor showed exophytic
      papillary proliferation with fibrovascular cores and consisted of atypical
      squamous epithelial cells. The tumor cells showed hyperchromasia, nuclear atypia,
      mitotic figures, apoptotic bodies, cancer pearls, and individual keratinization.
      Mild stromal invasion was seen. Therefore, PSCC was diagnosed. Koilocytosis,
      acantholytic features, and pseudovascular features were recognized in some areas.
      The lateral and vertical margins are negative for tumor cells. The mandibular
      bone was negative for tumor invasion. The pathological diagnosis was PSCC with
      koilocytotic, acantholytic and pseudovascular features. The patient was healthy
      and free from tumor three months after the operation.

PMID- 22135729
TI  - Well differentiated adenocarcinoma of the stomach composed of chief cell-like
      cells and parietal cells (Gastric adenocarcinoma of fundic gland type).
AB  - Gastric adenocarcinoma of fundic gland type is extremely rare. A 78-year-old
      Japanese man with carcinomatosis of unknown primary origin underwent upper
      gastrointestinal endoscopy. The endoscopy revealed an elevated lesion with
      central ulcer (1.3 * 2 * 1.5 cm) in the gastric corpus of fundic gland area. One
      biopsy was taken. The biopsy showed well differentiated adenocarcinoma. The
      adenocarcinoma was composed of basophilic chief cell-like cells and acidophilic
      parietal cells. The biopsy diagnosis was well differentiated adenocarcinoma of
      the stomach composed of chief cell-like cells and parietal cells (gastric
      adenocarcinoma of fundic gland type).

PMID- 22135730
TI  - Primary diffuse large B-cell lymphoma of the ethmoid sinus.
AB  - Malignant lymphoma of the ethmoid sinus is very rare. A case of diffuse large B
      cell lymphoma (DLBCL) of the left ethmoid sinus is presented here. A 79-year-old
      Japanese man was consulted to our hospital because of head ache and disturbance
      of left eye movement. Nasal endoscopy revealed a tumor, and imaging modalities
      including CT and MRI detected a tumor in the left ethmoid sinus. The tumor was
      invasive into left eye and left nose. A biopsy was performed via the nasal
      cavity. The biopsy revealed a diffuse proliferation of atypical lymphocytes. The
      atypical lymphocytes were large and had enlarged hyperchromatic nuclei. Mitotic
      figures were scattered. Hodgkin's cells were absent. Follicular structures were
      not seen. Immunohistochemically, the tumor cells were negative for cytokeratins
      (AE1/2, polyclonal, KL-1, and CAM5.2, Dako) and epithelial membrane antigen, CD3,
      CD15, CD30, CD45RO, and TdT. In contrast, the tumor cells were positive for CD20,
      CD45, CD79alpha, and p53. KI-67 labeling was 100%. Light chain restriction was
      present; there were numerous lambda-chain-positive cells, while kappa-chain
      positive cells were scant. The pathological diagnosis was DLBCL of the left
      ethmoid sinus. Imaging of the whole body revealed no tumors and lymphadenopathy
      other than the ethmoid DLBCL. The patient was treated with chemoradiation, and is
      now alive 3 months after the presentation. In conclusion, a very rare case of
      DLBCL of the ethmoid sinus was reported.

PMID- 22135731
TI  - A simplified method for stent placement in the distal duodenum: Enteroscopy
      overtube.
AB  - The treatment of choice for patients with unresectable neoplastic obstruction of
      the small intestine is the placement of expandable metal stents. However,
      endoscopic delivery from the distal duodenum can be more difficult. This case,
      shows the usefulness and technical advantages of the overtube and single balloon
      enteroscopy in the treatment of neoplastic stenosis affecting the small
      intestine.

PMID- 22135733
TI  - Physical activity: exploring views of older Russian-speaking slavic immigrants.
AB  - Many of the 1.3 million Russian-speaking immigrants in the US have chronic
      conditions such as cardiovascular disease, diabetes, obesity, and depression.
      They engage in physical activity less often than other groups, and little is
      known about their views of physical activity. This qualitative study explored
      physical activity attitudes, beliefs, motivators, and barriers among older
      Russian-speaking immigrants. In four focus group interviews, 23 participants
      discussed physical activity. "Movement is life" was a theme throughout all
      interviews. Walking was the most frequently mentioned activity. Increased energy
      and decreased pain were described as health benefits. Motivators for physical
      activity were maintaining function, improved health, and the support of God and
      family. Barriers included poor health and environmental safety concerns.
      Participants suggested community walking groups and church-supported programs as
      useful methods to promote physical activity. Future research includes developing
      culturally appropriate interventions that utilize physical activity to prevent
      and manage chronic illness with ethnic minority older adults.

PMID- 22135732
TI  - Voices that care: licensed practical nurses and the emotional labour underpinning
      their collaborative interactions with registered nurses.
AB  - Recognizing the emotional labour underlying interprofessional collaborations
      (IPCs) could be considered a crucial step towards building a cohesive nursing
      team. Although IPCs between registered nurses (RNs) and licensed practical nurses
      (LPNs) have been linked to quality nursing care, little is known about the
      emotions experienced by LPNs during their interactions with RNs or those factors
      that influence IPCs. A questionnaire administered to 309 LPNs found that (1) the
      professional identity of LPNs has evolved into a that of a unique social group;
      (2) LPNs define IPC as an interpersonal process of exploring similar or
      dissimilar assessments of a patient's status with RNs and, together, establishing
      a course of nursing actions; (3) the primary organizational factor facilitating
      IPCs is inclusive nursing leadership; (4) the interpersonal factor promoting IPCs
      is the level of trust RNs extend to LPNs; and (5) an LPN's emotional labour
      (i.e., internal emotional regulation) is most tangible during uncollaborative
      interactions with RNs.

PMID- 22135734
TI  - Newly Licensed RNs Describe What They Like Best about Being a Nurse.
AB  - About 25% of newly licensed registered nurses (NLRNs) leave their first job
      within two years, but only 2% leave the nursing profession in this same
      timeframe. Therefore, the researchers sought to discover what new nurses like
      best about being a nurse, in hopes of gaining information that might help
      facilities to reduce turnover rates. Data were collected between January and
      March 2009 from 1,152 NLRNs licensed in 15 US states. Krippendorff's method was
      used to analyze survey responses. Five themes emerged: "providing holistic
      patient care," "having an autonomous and collaborative practice," "using diverse
      knowledge and skills to impact patient outcomes," "receiving recognition," and
      "having a job that is secure and stimulating." Strategies are discussed that
      organizations might employ in helping NLRNs to realize what they best like about
      their work, which might lead to improved retention rates.

PMID- 22135735
TI  - Drugs for pain management in shock wave lithotripsy.
AB  - Objective. With this review, we provide a comprehensive overview of the main
      aspects and currently used drugs for analgesia in shockwave lithotripsy. Evidence
      Acquisition. We reviewed current literature, concentrating on newer articles and
      high-quality reviews in international journals. Results. No standardized
      protocols for pain control in SWL exist, although it is crucial for treatment
      outcome. General and spinal anaesthesia show excellent pain control but are only
      recommended for selected cases. The newer opioids and nonsteroidal anti
      inflammatory drugs are able to deliver good analgesia. Interest in inhalation
      anaesthesia with nitrous oxide, local anaesthesia with deep infiltration of the
      tissue, and dermal anaesthesia with EMLA or DMSO has recently rekindled, showing
      good results in terms of pain control and a favourable side effect profile.
      Tamsulosin and paracetamol are further well-known drugs being currently
      investigated. Conclusion. Apart from classically used drugs like opioids and
      NSARs, medicaments like nitrous oxide, paracetamol, DMSA, or refined
      administration techniques for infiltration anaesthesia show a good effectiveness
      in pain control for SWL.

PMID- 22135736
TI  - Bedside testing for chronic pelvic pain: discriminating visceral from somatic
      pain.
AB  - Objectives. This study was done to evaluate three bedside tests in discriminating
      visceral pain from somatic pain among women with chronic pelvic pain. Study
      Design. The study was an exploratory cross-sectional evaluation of 81 women with
      chronic pelvic pain of 6 or more months' duration. Tests included abdominal
      cutaneous allodynia (aCA), perineal cutaneous allodynia (pCA), abdominal and
      perineal myofascial trigger points (aMFTP) and (pMFTP), and reduced pain
      thresholds (RPTs). Results. Eighty-one women were recruited, and all women
      provided informed consent. There were 62 women with apparent visceral pain and 19
      with apparent somatic sources of pain. The positive predictive values for pelvic
      visceral disease were aCA-93%, pCA-91%, aMFTP-93%, pMFTP-81%, and RPT-79%. The
      likelihood ratio (+) and 95% C.I. for the detection of visceral sources of pain
      were aCA-4.19 (1.46, 12.0), pCA-2.91 (1.19, 7.11), aMTRP-4.19 (1.46, 12.0), pMFTP
      1.35 (0.86, 2.13), and RPT-1.14 (0.85, 1.52), respectively. Conclusions. Tests of
      cutaneous allodynia, myofascial trigger points, and reduced pain thresholds are
      easily applied and well tolerated. The tests for cutaneous allodynia appear to
      have the greatest likelihood of identifying a visceral source of pain compared to
      somatic sources of pain.

PMID- 22135737
TI  - Effect of diclofenac with B vitamins on the treatment of acute pain originated by
      lower-limb fracture and surgery.
AB  - The aim of this study was to compare the efficacy of diclofenac, for the
      treatment of acute pain originated by lower-limb fracture and surgery, with that
      of diclofenac plus B vitamins. This was a single-center, prospective, randomized,
      and double-blinded clinical trial. Patients with lower-limb closed fractures
      rated their pain on a 10 cm visual analog scale (VAS). Patients were then
      randomized to receive diclofenac or diclofenac plus B vitamins (thiamine,
      pyridoxine, and cyanocobalamin) intramuscularly twice daily. Patient evaluations
      of pain intensity were recorded throughout two periods: twenty-four hours
      presurgery and twenty-four hours postsurgical. One hundred twenty-two patients
      completed the study. The subjects' assessments of limb pain on the VAS showed a
      significant reduction from baseline values regardless of the treatment group.
      Diclofenac plus B vitamins combination was more effective to reduce the pain than
      diclofenac alone. The results showed that the addition of B vitamins to
      diclofenac increased its analgesic effect. The novelty of this paper consists in
      that diclofenac and diclofenac plus B vitamins were useful for treatment of acute
      pain originated by lower-limb fracture and surgery.

PMID- 22135738
TI  - The clinical concept of fibromyalgia as a changing paradigm in the past 20 years.
AB  - Fibromyalgia (FMS) is a valid clinical condition that affects 2%-4% of the
      population with a pivot symptom of widespread body pain. The cause and cure of
      FMS are as yet unknown. The concept of FMS has evolved over the past two decades
      to incorporate symptoms beyond pain as contributing to the global spectrum of
      suffering. FMS is now recognized to be grounded in the neurological domain with
      evidence of dysregulation of pain processing. Appreciation of the
      neurophysiologic mechanisms operative in FMS has contributed to rational
      treatment recommendations, although a "gold standard treatment" does not
      currently exist. Ideal treatments for FMS patients should be individualized with
      emphasis on active patient participation, good health practices, and multimodal
      intervention, incorporating nonpharmacologic and pharmacologic treatments.
      Predictors of outcome, which is favourable in over 50% of patients, are unknown,
      but those with better outcome do more physical activity and use fewer
      medications.

PMID- 22135739
TI  - Neurobiology underlying fibromyalgia symptoms.
AB  - Fibromyalgia is characterized by chronic widespread pain, clinical symptoms that
      include cognitive and sleep disturbances, and other abnormalities such as
      increased sensitivity to painful stimuli, increased sensitivity to multiple
      sensory modalities, and altered pain modulatory mechanisms. Here we relate
      experimental findings of fibromyalgia symptoms to anatomical and functional brain
      changes. Neuroimaging studies show augmented sensory processing in pain-related
      areas, which, together with gray matter decreases and neurochemical abnormalities
      in areas related to pain modulation, supports the psychophysical evidence of
      altered pain perception and inhibition. Gray matter decreases in areas related to
      emotional decision making and working memory suggest that cognitive disturbances
      could be related to brain alterations. Altered levels of neurotransmitters
      involved in sleep regulation link disordered sleep to neurochemical
      abnormalities. Thus, current evidence supports the view that at least some
      fibromyalgia symptoms are associated with brain dysfunctions or alterations,
      giving the long-held "it is all in your head" view of the disorder a new meaning.

PMID- 22135740
TI  - Gastro-oesophageal reflux in noncystic fibrosis bronchiectasis.
AB  - The clinical presentation of noncystic fibrosis bronchiectasis may be complicated
      by concomitant conditions, including gastro-oesophageal reflux (GOR). Increased
      acidic GOR is principally caused by gastro-oesophageal junction incompetence and
      may arise from lower oesophageal sphincter hypotension, including transient
      relaxations, hiatus hernia, and oesophageal dysmotility. Specific
      pathophysiological features which are characteristic of respiratory diseases
      including coughing may further increase the risk of GOR in bronchiectasis. Reflux
      may impact on lung disease severity by two mechanisms, reflex bronchoconstriction
      and pulmonary microaspiration. Symptomatic and clinically silent reflux has been
      detected in bronchiectasis, with the prevalence of 26 to 75%. The cause and
      effect relationship has not been established, but preliminary reports suggest
      that GOR may influence the severity of bronchiectasis. Further studies examining
      the implications of GOR in this condition, including its effect across the
      disease spectrum using a combination of diagnostic tools, will clarify the
      clinical significance of this comorbidity.

PMID- 22135741
TI  - Effect and safety of mycophenolate mofetil in idiopathic pulmonary fibrosis.
AB  - Background. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic
      interstitial lung disease with ineffective treatment. Mycophenolate mofetil (MMF)
      is an immunomodulatory agent which inhibits lymphocyte proliferation. Objective.
      We sought to determine the safety and efficacy profile of MMF in IPF patients.
      Methods. We retrospectively identified ten patients, who met the ATS/ERS 2000
      criteria for IPF and received MMF 2 gr/day for 12 months. All of them had routine
      laboratory, pulmonary function and radiological (high resolution computed
      tomography-HRCT) data available and were enrolled in the study. Forced vital
      capacity (FVC), total lung capacity (TLC), diffusion capacity of the lung for
      carbon monoxide (DL(CO)), 6-minute walking distance (6MWD), HRCT scans and
      routine laboratory data at treatment onset were compared with respective values
      12 months after treatment onset. Results. There were no significant alterations
      in FVC, TLC, DL(CO) and 6MWD pre- and 6 and 12 months post-treatment. HRCT
      evaluation showed deterioration of the total extent of disease (P = 0.002) and
      extent of ground-glass opacity (P = 0.02). No cases of clinically significant
      infection, leucopenia, or elevated liver enzymes were recorded. Conclusions. MMF
      is a safe therapeutic modality which failed to show a beneficial effect both in
      functional and radiological parameters in a small cohort of IPF patients.

PMID- 22135742
TI  - Successful use of extracorporeal life support after double traumatic
      tracheobronchial injury in a patient with severe acute asthma.
AB  - We report the case of an asthmatic patient with blunt trachea and left main
      bronchus injuries who developed acute severe asthma after surgical repair.
      Despite medical treatment and ventilatory support, asthma persisted with high
      airway pressures and severe respiratory acidosis. We proposed venovenous
      extracorporeal life support for CO(2) removal which allowed arterial blood gas
      normalization and airway pressures decrease. Extracorporeal life support was
      removed on day five after medical treatment of acute severe asthma. So we report
      the successful use of extracorporeal life support for operated double blunt
      tracheobronchial injury with acute severe asthma.

PMID- 22135743
TI  - The PPARgamma Agonist Rosiglitazone Is Antifibrotic for Scleroderma Lung
      Fibroblasts: Mechanisms of Action and Differential Racial Effects.
AB  - We present novel data demonstrating that the expression of PPARgamma is reduced
      in lung fibroblasts from black SSc-ILD patients as compared to white patients.
      Activating PPARgamma with the agonist rosiglitazone increased the expression of
      MMP-1 and inhibited collagen type I in lung fibroblasts isolated from white, but
      not black, SSc-ILD patients. Blocking the c-Met receptor abolishes
      rosiglitazone's effects on collagen and MMP-1 in lung fibroblasts isolated from
      white SSc-ILD patients, while augmenting the expression of the c-Met receptor in
      fibroblasts from black SSc-ILD patients replicates the effects of rosiglitazone
      seen in whites. We conclude that PPARgamma agonists warrant consideration as
      potential antifibrotic drugs in patients with SSc-ILD. Differential therapeutic
      effects might be anticipated especially relative to racial differences and the
      functional expression of the c-Met receptor.

PMID- 22135744
TI  - Dopamine dysregulation syndrome and deep brain stimulation of the subthalamic
      nucleus in Parkinson's disease.
AB  - Dopamine dysregulation syndrome is a complication of the dopaminergic treatment
      in Parkinson's disease that may be very disabling due to the negative impact that
      compulsive medication use may have on patients' social, psychological, and
      physical functioning. The relationship between subthalamic nucleus deep brain
      stimulation and dopamine dysregulation syndrome in patients with Parkinson's
      disease remains unclear. Deep brain stimulation may improve, worsen, or have no
      effect on preoperative dopamine dysregulation syndrome. Moreover, dopamine
      dysregulation syndrome may appear for the first time after deep brain stimulation
      of the subthalamic nucleus. The outcome of postoperative dopamine dysregulation
      syndrome is poor despite stimulation and medication adjustments. Here we review
      the phenomenology and neurobiology of this disorder, discuss possible mechanisms
      that may underlie the diverse outcomes of dopamine dysregulation syndrome after
      subthalamic nucleus deep brain stimulation, and propose management strategies.

PMID- 22135745
TI  - Infection-induced vulnerability of perinatal brain injury.
AB  - A growing body of evidence demonstrates that susceptibility and progression of
      both acute and chronic central nervous system disease in the newborn is closely
      associated with an innate immune response that can manifest from either direct
      infection and/or infection-triggered damage. A common feature of many of these
      diseases is the systemic exposure of the neonate to bacterial infections that
      elicit brain inflammation. In recent years, the importance of innate immune
      receptors in newborn brain injury, the so-called Toll-like receptors, has been
      demonstrated. In this paper we will discuss how neonatal sepsis, with particular
      emphasis on Escherichia coli, coagulase-negative staphylococci, and group B
      streptococcal infections in preterm infants, and Toll-like receptor-mediated
      inflammation can increase the vulnerability of the newborn brain to injury.

PMID- 22135746
TI  - Imaging the visual pathway in neuromyelitis optica.
AB  - The focus of this paper is to summarize the current knowledge on visual pathway
      damage in neuromyelitis optica (NMO) assessed by magnetic resonance imaging (MRI)
      and optical coherence tomography (OCT).

PMID- 22135747
TI  - A retrospective study on pathologic features and racial disparities in prostate
      cancer.
AB  - We reviewed more than 3,000 pathology reports on prostate cancer-related surgical
      specimens and analyzed racial disparities in histological and clinical features
      at the time of initial biopsy, diagnosis of prostate cancer, and prostatectomy,
      as well as in characteristics of tumor evolution between African American and
      Caucasian patients. As compared to Caucasians, African American patients had
      younger age, higher cancer detection rate, higher Gleason score of prostate
      cancer, and more bilateral involvement of the prostate. African Americans also
      had larger prostates, greater volume of tumor, and more positive margins. The
      diagnosis of HGPIN or ASAP in prostate biopsies and African American race
      conferred an increased risk of diagnosis of prostate cancer. The interval between
      prior noncancerous biopsy and the subsequent biopsy with diagnosis of prostate
      cancer was shorter in men with HGPIN, with ASAP, or of African American race.

PMID- 22135748
TI  - Role of heparan sulfate 2-o-sulfotransferase in prostate cancer cell
      proliferation, invasion, and growth factor signaling.
AB  - Heparan-sulfate proteoglycans (HSPGs) are required for maximal growth factor
      signaling in prostate cancer progression. The degree of sulfate modification on
      the covalently attached heparan sulfate (HS) chains is one of the determining
      factors of growth factor-HSPG interactions. Sulfate groups are transferred to HS
      chains via a series of O-sulfotransferases. In the present study, we demonstrate
      that Heparan sulfate 2-O-sulfotransferase (2OST) is essential for maximal
      proliferation and invasion of prostate cancer cells in the LNCaP-C4-2B model. We
      also show that a decrease in invasion due to 2OST siRNA is associated with an
      increase in actin and E-cadherin accumulation at the cell surface. 2OST
      expression correlates with increasing metastatic potential in this model. We
      demonstrate that 2OST expression is upregulated by the stress-inducible
      transcription factors HIF1alpha, ATF2, and NFkappaB. Chromatin
      immunoprecipitation analysis suggests that HIF1alpha and ATF2 act directly on the
      2OST promoter, while NFkappaB acts indirectly.

PMID- 22135749
TI  - Three trocars laparoscopic resection of angiomyolipoma of the liver.
AB  - Angiomyolipoma of the liver (AML) is an infrequent neoplasm composed of three
      tissues (adipose, muscle and vessels). In spite of advances in radiology,
      preoperative correct diagnosis is difficult. Clasically, a conservative
      management strategy was adopted in patients with asymptomatic tumors less than 5
      cm with undoubtful diagnosis. But after publishing some few cases of malignant
      angiomyolipoma a more radical has been advocated. Laparoscopic resection of liver
      tumors is becoming a excellent approach for operating on benign liver tumors.
      Usually is performed using five trocars but in some cases a less invasive
      technique with three trocars could be used. We present a laparoscopic resection
      of liver angiomyolipoma in a 65 year-old male using only three trocars and also
      discuss the optimal management of AML and technical tips of three-trocar
      technique.

PMID- 22135750
TI  - Liver resection after downstaging hepatocellular carcinoma with sorafenib.
AB  - Background. Sorafenib is a molecular-targeted therapy used in palliative
      treatment of advanced hepatocellular carcinoma in Child A patients. Aims. To
      address the question of sorafenib as neoadjuvant treatment. Methods. We describe
      the cases of 2 patients who had surgery after sorafenib. Results. The patients
      had a large hepatocellular carcinoma in the right liver with venous neoplastic
      thrombi (1 in the right portal branch, 1 in the right hepatic vein). After 9
      months of sorafenib, reassessment showed that tumours had decreased in size with
      a necrotic component. A right hepatectomy with thrombectomy was performed, and
      histopathology showed 35% to 60% necrosis. One patient had a recurrence after 6
      months and had another liver resection; they are both recurrence-free since then.
      Conclusion. Sorafenib can downstage hepatocellular carcinoma and thus could
      represent a bridge to surgery. It may be possible to select patients in good
      general condition with partial regression of the tumour with sorafenib for a
      treatment in a curative intent.

PMID- 22135751
TI  - Relationship of exercise volume with change in depression and its association
      with self-efficacy to control emotional eating in severely obese women.
AB  - Introduction. Exercise may improve one's perceived ability to control overeating
      related to negative emotions through psychological pathways such as reduced
      depression; however, the volume required is unclear. Methods. Severely obese
      women (N = 88) participated in a 24-week exercise and nutrition treatment
      incorporating self-regulatory skills training, and were assessed on depression,
      self-efficacy, self-regulatory skills usage, weight, and waist circumference, at
      baseline and treatment end. Results. Subjects completing low-moderate (40-149.9
      minutes/week) and public health (>=150 minutes/week) volumes of exercise had
      significant and similar reductions in depression scores. No significant changes
      were found for those completing <40 minutes/week. For all subjects aggregated,
      depression change was significantly related to change in self-efficacy to control
      emotional eating; however, this relationship was completely mediated by changes
      in self-regulatory skill usage. When changes in depression, self-efficacy, and
      self-regulatory skills usage were entered into multiple regression equations as
      predictors, only self-regulatory skill changes explained significant unique
      portions of the overall variance in weight and weight circumference change.
      Discussion. Exercise of less than half the public health recommendation was
      associated with depression improvement, with no dose-response effect. Changes in
      depression, self-efficacy, and self-regulation may be salient variables to
      account for in behavioral weight-loss treatment research.

PMID- 22135752
TI  - From 1994's "Physical Disability" to 2011's "Advances in Disability Research".

PMID- 22135753
TI  - Disability research: progress made, opportunities for even greater gains.

PMID- 22135754
TI  - An appreciation of Stephen M. Haley.

PMID- 22135755
TI  - Clonal hypereosinophilic syndrome: two cases report in black men from sub-saharan
      Africa and literature reviews.
AB  - The first case is about a man of 60 years old suffering of hypereosinophilic
      syndrome (HES) developed since 1998. He presented chronic cough, insomnia, and
      negative parasitical test. We observed hypereosinophilia and fibroblastic
      hyperplasia at the bone marrow biopsy. Initially, hydroxyurea and alpha
      interferon treatment failed. We proposed to him imatinib mesylate in May 2003.
      The FIP1L1-PDGFRA gene was detected. The second case is about a man of 34 years
      old seen in March 2002. First investigation concluded to CML. Progressively,
      eosinophil cells increased, and complications occurred as oedema syndrome,
      dyspnoea, and parietal chronic endocarditic fibrosis associated with
      pericarditis. In addition, a bowel obstruction happened and was cured by surgery.
      Bcr-abl fusion was negative, and FIP1L1-PDGFRA gene was detected after and
      imatinib mesylate was given. Actually, endocarditic fibrosis decreased. The two
      patients are in haematological and cytogenetic remission. We concluded that
      clonal HES is present in Africa, and imatinib mesylate is effective.

PMID- 22135756
TI  - Place cells, grid cells, attractors, and remapping.
AB  - Place and grid cells are thought to use a mixture of external sensory information
      and internal attractor dynamics to organize their activity. Attractor dynamics
      may explain both why neurons react coherently following sufficiently large
      changes to the environment (discrete attractors) and how firing patterns move
      smoothly from one representation to the next as an animal moves through space
      (continuous attractors). However, some features of place cell behavior, such as
      the sometimes independent responsiveness of place cells to environmental change
      (called "remapping"), seem hard to reconcile with attractor dynamics. This paper
      suggests that the explanation may be found in an anatomical separation of the two
      attractor systems coupled with a dynamic contextual modulation of the connection
      matrix between the two systems, with new learning being back-propagated into the
      matrix. Such a scheme could explain how place cells sometimes behave coherently
      and sometimes independently.

PMID- 22135757
TI  - Deafferentation-induced redistribution of MMP-2, but not of MMP-9, depends on the
      emergence of GAP-43 positive axons in the adult rat cochlear nucleus.
AB  - The matrix metalloproteinases MMP-9 and MMP-2, major modulators of the
      extracellular matrix (ECM), were changed in amount and distribution in the rat
      anteroventral cochlear nucleus (AVCN) following its sensory deafferentation by
      cochlear ablation. To determine what causal relationships exist between the
      redistribution of MMP-9 and MMP-2 and deafferentation-induced reinnervation,
      kainic acid was stereotaxically injected into the ventral nucleus of the
      trapezoid body (VNTB) prior to cochlear ablation, killing cells that deliver the
      growth associated protein 43 (GAP-43) into AVCN. Deafferentation-induced changes
      in the pattern of MMP-9 staining remained unaffected by VNTB lesions. By
      contrast, changes in the distribution of MMP-2 normally evoked by sensory
      deafferentation were reversed if GAP-43 positive axons were prevented to grow in
      AVCN. In conclusion, GAP-43-containing axons emerging in AVCN after cochlear
      ablation seem to be causal for the maintenance of MMP-2-mediated ECM remodeling.

PMID- 22135758
TI  - Cortical plasticity during motor learning and recovery after ischemic stroke.
AB  - The motor system has the ability to adapt to environmental constraints and injury
      to itself. This adaptation is often referred to as a form of plasticity allowing
      for livelong acquisition of new movements and for recovery after stroke. We are
      not sure whether learning and recovery work via same or similar neural
      mechanisms. But, all these processes require widespread changes within the matrix
      of the brain. Here, basic mechanisms of these adaptations on the level of
      cortical circuitry and networks are reviewed. We focus on the motor cortices
      because their role in learning and recovery has been investigated more thoroughly
      than other brain regions.

PMID- 22135759
TI  - The influence of dopamine on automatic and controlled semantic activation in
      Parkinson's disease.
AB  - Two semantic priming tasks, designed to isolate automatic and controlled semantic
      activation, were utilized to investigate the impact of dopamine depletion on
      semantic processing in Parkinson's disease (PD). Seven people with PD (tested
      whilst on and off levodopa medication) and seven healthy adults participated in
      the study. The healthy adult participants demonstrated intact automatic and
      controlled semantic activation. Aberrant controlled semantic activation was
      observed in the PD group on levodopa; however, automatic semantic activation was
      still evident. In contrast, automatic semantic activation was not evident in the
      PD group off levodopa. These results further clarify the impact of PD on semantic
      processing, demonstrating that dopamine depletion can cause disturbances in both
      automatic and controlled semantic activation.

PMID- 22135760
TI  - Sentence comprehension and its association with executive functions in patients
      with Parkinson's disease.
AB  - Coexistent impairments in executive functions and language comprehension in
      patients with Parkinson's disease (PD) have been repeatedly observed. In this
      study, the aim was to provide insights into the interaction between linguistic
      representation and processing and executive functioning. Therefore, sentence
      comprehension and executive functions were assessed in 28 Dutch-speaking PD
      patients and 28 healthy control subjects. Three aspects of the sentence materials
      were varied: (1) phrase structure complexity, (2) sentence length, and (3)
      picture congruence. PD patients with mild-to-moderate disease severity showed
      decreased sentence comprehension compared to healthy control subjects. The
      difficulties encountered by PD patients were not limited to one aspect of the
      sentence materials. The same pattern of results was present in healthy control
      subjects. Deficits in set-switching were specifically associated with the
      comprehension of passive sentences. Generally, our study confirms that there does
      not appear to be a language faculty encapsulated from the influence of executive
      functions.

PMID- 22135761
TI  - Comparing the Mini-BESTest with the Berg Balance Scale to Evaluate Balance
      Disorders in Parkinson's Disease.
AB  - Objective. The purpose of this study was to explore the usefulness of the Mini
      BESTest compared to the Berg Balance Scale in evaluating balance in people with
      PD of varying severity. We evaluated (1) the distribution of patients scores to
      look for ceiling effects, (2) concurrent validity with severity of disease, and
      (3) the sensitivity/specificity of separating people with or without postural
      response deficits. Subjects. Ninety-seven people with PD were tested for balance
      deficits using the Berg, Mini-BESTest, Unified Parkinson's Disease Rating Scale
      (UPDRS) III and the Hoehn & Yahr (H&Y) disease severity classification. Setting.
      Clinical research facility at Oregon Health & Science University. Results. The
      Mini-BESTest is highly correlated with the Berg (r = 0.79, P < 0.001), but avoids
      the ceiling compression effect of the Berg for mild PD (skewness -2.30 Berg, 
      0.93 Mini-BESTest). Consequently, the Mini-BESTest is more effective than the
      Berg for predicting UPDRS Motor score (P < 0.001 Mini-BESTest versus P = 0.86
      Berg), and for discriminating between those with and without postural response
      deficits as measured by the H&Y (ROC differential P = 0.06). Conclusion. The Mini
      BESTest is a promising tool for discerning balance deficits in patients with PD,
      most importantly those with more subtle deficits.

PMID- 22135762
TI  - Cognitive rehabilitation for executive dysfunction in Parkinson's disease:
      application and current directions.
AB  - Cognitive dysfunction in Parkinson's disease contributes to disability, caregiver
      strain, and diminished quality of life. Cognitive rehabilitation, a behavioral
      approach to improve cognitive skills, has potential as a treatment option to
      improve and maintain cognitive skills and increase quality of life for those with
      Parkinson's disease-related cognitive dysfunction. Four cognitive rehabilitation
      programs in individuals with PD are identified from the literature.
      Characteristics of the programs and outcomes are reviewed and critiqued. Current
      studies on cognitive rehabilitation in PD demonstrate feasibility and
      acceptability of a cognitive rehabilitation program for patients with PD, but are
      limited by their small sample size and data regarding generalization of effects
      over the long term. Because PD involves progressive heterogeneous physical,
      neurological, and affective difficulties, future cognitive rehabilitation
      programs should aim for flexibility and individualization, according to each
      patient's strengths and deficits.

PMID- 22135763
TI  - Effectiveness of an inpatient movement disorders program for patients with
      atypical parkinsonism.
AB  - This paper investigated the effectiveness of an inpatient movement disorders
      program for patients with atypical parkinsonism, who typically respond poorly to
      pharmacologic intervention and are challenging to rehabilitate as outpatients.
      Ninety-one patients with atypical parkinsonism participated in an inpatient
      movement disorders program. Patients received physical, occupational, and speech
      therapy for 3 hours/day, 5 to 7 days/week, and pharmacologic adjustments based on
      daily observation and data. Differences between admission and discharge scores
      were analyzed for the functional independence measure (FIM), timed up and go test
      (TUG), two-minute walk test (TMW), Berg balance scale (BBS) and finger tapping
      test (FT), and all showed significant improvement on discharge (P > .001).
      Clinically significant improvements in total FIM score were evident in 74% of the
      patients. Results were similar for ten patients whose medications were not
      adjusted. Patients with atypical parkinsonism benefit from an inpatient
      interdisciplinary movement disorders program to improve functional status.

PMID- 22135767
TI  - Fine-needle aspiration cytology: an advancing horizon.

PMID- 22135765
TI  - Reliability in one-repetition maximum performance in people with Parkinson's
      disease.
AB  - Strength training is an effective modality to improve muscular strength and
      functional performance in people with Parkinson's disease (PWP). One-repetition
      maximum (1-RM) is the gold standard assessment of strength; however, PWP suffer
      from day-to-day variations in symptom severity and performance characteristics,
      potentially adversely affecting the reliability of 1-RM performance. Herein, we
      assessed the reliability of 1-RM in PWP. Forty-six participants completed two
      sessions of 1-RM testing of knee extension, knee flexion, chest press, and biceps
      curl at least 72 hours apart. Significantly differences between testing sessions
      were identified for knee extension (P < 0.001), knee flexion (P = 0.042), and
      biceps curl (P = 0.001); however, high reliability (ICC > 0.90) was also
      identified between sessions. Interestingly, almost third of subjects failed to
      perform better on the second testing session. These findings suggest that 1-RM
      testing can be safely performed in PWP and that disease-related daily variability
      may influence 1-RM performance.

PMID- 22135764
TI  - A review of dual-task walking deficits in people with Parkinson's disease: motor
      and cognitive contributions, mechanisms, and clinical implications.
AB  - Gait impairments in Parkinson's disease (PD) are exacerbated under dual-task
      conditions requiring the simultaneous performance of cognitive or motor tasks.
      Dual-task walking deficits impact functional mobility, which often requires
      walking while performing concurrent tasks such as talking or carrying an object.
      The consequences of gait impairments in PD are significant and include increased
      disability, increased fall risk, and reduced quality of life. However, effective
      therapeutic interventions for dual-task walking deficits are limited. The goals
      of this narrative review are to describe dual-task walking deficits in people
      with PD, to discuss motor and cognitive factors that may contribute to these
      deficits, to review potential mechanisms underlying dual-task deficits, and to
      discuss the effect of therapeutic interventions on dual-task walking deficits in
      persons with PD.

PMID- 22135766
TI  - Association between AgNORs and Immunohistochemical Expression of ER, PR,
      HER2/neu, and p53 in Breast Carcinoma.
AB  - Settings. Despite the limited diagnostic utility of AgNORs (argyrophilic
      nucleolar organiser region-associated proteins) for individual breast lesions,
      AgNOR analysis bears a significant potential for characterizing cell
      proliferative activity of breast lesions. Methodology. The present study
      investigated the relationship between mean AgNORs count and immunohistochemical
      expression of ER, PR, HER2/neu, and p53 in breast carcinoma in serial paraffin
      sections from 137 breast carcinomas. Twenty control cases of benign breast
      lesions were included. Results. Mean AgNOR counts correlated significantly
      inversely with hormone estrogen receptors (ER), Progesterone receptors (PR), and
      p53 immunohistochemical expression, denoting P values of 0.05, 0.01, and 0.001,
      respectively. No significant correlation was found between mean AgNOR counts and
      HER2/neu, P = 0.9. Mean AgNOR count was significantly higher in grade II tumor
      cells. We conclude that mean AgNOR counts correlate with ER, PR, and P53 tumor
      markers in breast carcinomas. Conclusion. We recommend the use of mean AgNOR
      count for accurate reporting of breast carcinomas, as well as prediction of ER,
      PR, and P53 in routine paraffin sections.

PMID- 22135768
TI  - Value of Procollagen Type I Aminoterminal Propeptide in Women with Breast Cancer
      with regard to Metastases.
AB  - Background. The aim of this study was to show the importance of the bone marker
      procollagen type 1 aminoterminal propeptide (P1NP) in detecting bone metastases
      in women suffering from breast cancer. We furthermore investigated to what degree
      P1NP is correlated to the degree of bone metastases, and if P1NP is increased in
      patients with metastases other than bone. Patients and Methods. We analyzed 80
      serum samples of women (17 premenopausal/63 postmenopausal) with breast cancer.
      Therefore we used a specific immunoassay "ELECSYS 2010" by Roche Diagnostics. We
      divided our group of patients with regard to menopausal status, sites of
      metastases and number of bone metastases. Results. As a result we found higher
      concentrations of P1NP in women with radiologically confirmed bone metastases
      (median: 125.75 ng/mL) in comparison to the collective without bone involvement
      (median: 73.61 ng/mL). However, both groups showed values above the applied
      cutoff values of median 27.8 ng/mL for premenopausal women and median: 37.1 ng/mL
      for the postmenopausal group due to the fact that all patients had cancer.
      Furthermore higher P1NP concentrations were found in women with more than 5 sites
      of bone metastases (median: 183.9 ng/mL) than in patients with only one site of
      bone metastases (median: 37 ng/mL). Also patients with no bone involvement but
      other sites of metastases showed quite high P1NP concentrations (median: 73.61
      ng/mL). Conclusion. The marker of bone turnover procollagen type 1 aminoterminal
      propeptide can be considered as a useful tool for estimating the extent of bone
      involvement and for the detection of bone metastases. P1NP cannot replace
      conventional methods for detecting bone metastases such as radiological methods
      but it can help clarify unclear radiological results. This study does not take
      into account the change of P1NP concentration during the course of therapy.

PMID- 22135770
TI  - Is Near-Infrared Spectroscopy a Reliable Method to Evaluate Clamping Ischemia
      during Carotid Surgery?
AB  - Guidelines do not include cerebral oximetry among monitoring for carotid
      endarterectomy (CEA). The purpose of this study was to evaluate the reliability
      of near-infrared spectroscopy (NIRS) in the detection of clamping ischemia and in
      the prevention of clamping-related neurologic deficits using, as a cutoff for
      shunting, a 20% regional cerebral oxygen saturation (rSO(2)) decrease if
      persistent more than 4 minutes, otherwise a 25% rSO(2) decrease. Bilateral rSO(2)
      was monitored continuously in patients undergoing CEA under general anesthesia
      (GA). Data was recorded after clamping, declamping, during shunting and lowest
      values achieved. Preoperative neurologic, CT-scan, and vascular lesions were
      recorded. We reviewed 473 cases: 305 males (64.5%) mean age 73.3 +/- 7.3. Three
      patients presented transient ischemic deficits at awakening, no perioperative
      stroke or death; 41 (8.7%) required shunting: 30 based on the initial rSO(2)
      value and 11 due to a decrease during surgery. Using the ROC curve analysis we
      found, for a >25% reduction from baseline value, a sensitivity of 100% and a
      specificity of 90.6%. Reliability, PPV, and NPV were 95.38%, 9%, and 100%,
      respectively. In conclusion, this study indicates the potential reliability of
      NIRS monitoring during CEA under GA, using a cutoff of 25% or a cutoff of 20% for
      prolonged hypoperfusion.

PMID- 22135769
TI  - Gene-drug interaction in stroke.
AB  - Stroke is the third cause of mortality and one of most frequent causes of long
      term neurological disability, as well as a complex disease that results from the
      interaction of environmental and genetic factors. The focus on genetics has
      produced a large number of studies with the objective of revealing the genetic
      basis of cerebrovascular diseases. Furthermore, pharmacogenetic research has
      investigated the relation between genetic variability and drug
      effectiveness/toxicity. This review will examine the implications of
      pharmacogenetics of stroke; data on antihypertensives, statins, antiplatelets,
      anticoagulants, and recombinant tissue plasminogen activator will be illustrated.
      Several polymorphisms have been studied and some have been associated with
      positive drug-gene interaction on stroke, but the superiority of the genotype
      guided approach over the clinical approach has not been proved yet; for this
      reason, it is not routinely recommended.

PMID- 22135771
TI  - Hemispheric asymmetry of visual cortical response by means of functional
      transcranial Doppler.
AB  - We assessed the visual evoked response and investigated side-to-side differences
      in mean blood flow velocities (MBFVs) by means of functional transcranial Doppler
      (fTCD) in 49 right-handed patients with severe internal carotid artery (ICA)
      stenosis and 30 healthy volunteers, simultaneously in both posterior cerebral
      arteries (PCAs) using 2 MHz probes, successively in the dark and during the white
      light stimulation. Statistically significant correlation (P = 0.001) was shown in
      healthy and in patients (P < 0.05) between MBFV in right PCA in physiological
      conditions and MBFV in right PCA during the white light stimulation and in the
      dark. The correlation between MBVF in right PCA and contralateral left PCA was
      not statistically significant (P > 0.05). The correlation between ipsilateral
      left PCA was significantly higher than the one with contralateral right PCA (P <
      0.05). There is a clear trend towards the lateralisation of the visual evoked
      response in the right PCA.

PMID- 22135772
TI  - A basic strategy to manage global health with reference to livestock production
      in Asia.
AB  - Newly emerging infectious diseases (nEIDs) have increased rapidly presenting
      alarming challenges to global health. We argue that for effective management of
      global health a basic strategy should include at least three essential tactical
      forms: actions of a directly focused nature, institutional coordination, and
      disciplinary integration in approaches to health management. Each level of action
      is illustrated with examples from the livestock sector in Asia. No clear example
      of all three tactical forms in place can be found from developing countries where
      food security is a significant threat although Vietnam is developing a
      comprehensive strategy. Finally, an ecosystem health approach to global health
      management is advocated; such an approach moves away from the traditional single
      disciplinary approach. Stronger guidance is needed to direct ecohealth research
      and application in the management of global health.

PMID- 22135776
TI  - Tracing the pathogen Staphylococcus aureus on laboratory ants using physical
      preconcentration coupled ZnO nanoparticle assisted MALDI-TOF MS.
AB  - Ants and humans coexist closely and for the most part happily. We consider ants
      to be harmless, small beings--we have no problem picking them out of our tea cups
      or sugar jars, throwing them away and continuing to consume the food. This paper
      is an eye-opener that these ants are not as harmless as they may seem. In
      particular, our relationship with those present in bacteria-rich environments
      (e.g. a microbiological lab) need to be reconsidered. From an analytical point of
      view we have applied the physical preconcentration coupled ZnO NPs assisted MALDI
      MS (PP-MALDI-MS) as a novel and sensitive technique for detecting bacteria on the
      surface of a species of ant present in our laboratory. The preconcentration
      methods consist of simple techniques comprising of vortex combined with
      centrifugation or ultrasonication resulting in increasing sample concentration up
      to the MALDI-MS detection limit. ZnO NPs were used to further enhance the
      bacterial signals for culture free rapid analysis using MALDI-MS. The importance
      of a vortex-combined centrifugation approach, using a large number of samples
      (large number of ants) and decreasing the suspension volume and addition of
      sample to ZnO NPs (3.5g L(-1)) were found to be crucial prerequisites for
      increasing MALDI-MS detection of bacteria on ants. We were able to identify the
      pathogenic clinically important Staphylococcus aureus on the surface of the ants.
      The bacterial identification was validated using ClinPro 2.1.

PMID- 22135777
TI  - Amperometric determination of xanthine in fish meat by zinc oxide
      nanoparticle/chitosan/multiwalled carbon nanotube/polyaniline composite film
      bound xanthine oxidase.
AB  - Xanthine oxidase (XOD) was immobilized on a composite film of zinc oxide
      nanoparticle/chitosan/carboxylated multiwalled carbon nanotube/polyaniline (ZnO
      NP/CHIT/c-MWCNT/PANI) electrodeposited over the surface of a platinum (Pt)
      electrode. A xanthine biosensor was fabricated using XOD/ZnO-NP/CHIT/c
      MWCNT/PANI/Pt as working electrode, Ag/AgCl as reference electrode and Pt wire as
      auxiliary electrode connected through a potentiostat. The ZnO-NPs were
      characterized by X-ray diffraction (XRD) and transmission electron microscopy
      (TEM), and the enzyme electrode was characterized by cyclic voltammetry, scanning
      electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and
      electrochemical impedance spectroscopy (EIS). The biosensor showed optimum
      response within 4 s at 0.5 V potential, pH 7.0, 35  degrees C and linear range
      0.1-100 MUM with a detection limit of 0.1 MUM. The enzyme electrode was employed
      for determination of xanthine in fish meat during storage. The electrode lost 30%
      of its initial activity after 80 uses over one month, when stored at 4  degrees
      C.

PMID- 22135778
TI  - Novel cathodic electrochemiluminescence of tris(bipyridine) ruthenium(II) on a
      gold electrode in acidic solution.
AB  - The novel phenomenon of cathodic electrochemiluminescence on a gold electrode in
      tris(bipyridine) ruthenium(II) (Ru(bpy)(3)(2+)) solution is described for the
      first time. A cathodic electrochemiluminescence (ECL) was found to mainly occur
      at 0.4-0.8 V with continuous potential scanning from 0.2-1.4 V and the ECL peak
      was observed around 0.68 V, which was quite different from generally reported
      Ru(bpy)(3)(2+) ECL. Our group speculated that Ru(bpy)(3)(2+) possibly reacts with
      the gold electrode in the acidic phosphate buffer solution (PBS) to generate
      luminescence. The possible ECL mechanism was discussed according to the presented
      results. Moreover, it is revealed that the Au as co-reactant in the Ru-system
      contributed dominantly to the whole ECL. Therefore, the reaction between
      Ru(bpy)(3)(2+) and the newly formed Au implied that the inert metal Au could
      become a promising material for ECL investigations.

PMID- 22135779
TI  - Response to letter by Freeman et al regarding article, "Very early mobilization
      after stroke fast-tracks return to walking: further results from the phase II
      AVERT randomized controlled trial".

PMID- 22135780
TI  - Investments in healthcare: observations of a changing landscape in manuscript
      submissions.

PMID- 22135781
TI  - Continence Coach: Eliminating moisture-associated skin damage: continual devotion
      to continence care.

PMID- 22135782
TI  - Special to OWM: Clinicians speak out: innovations in products and practice.

PMID- 22135783
TI  - Guest editor's introduction: special section on the Symposium on Interactive 3D
      Graphics and Games (I3D).

PMID- 22135784
TI  - Guest editors' introduction: special section on the IEEE International Symposium
      on Mixed and Augmented Reality (ISMAR).

PMID- 22135785
TI  - Safe splinting in hand surgery  (original author response).

PMID- 22135786
TI  - Evaluating the curriculum by  using the SPICES model at  King Khalid University 
      Medical School.

PMID- 22135787
TI  - "Cells to Society": a course that introduces new students to medicine's ideals,
      values, and culture.

PMID- 22135788
TI  - Improving medical  management and  leadership development  in undergraduates.

PMID- 22135789
TI  - Peer-assisted learning  improves prescribing skills.

PMID- 22135790
TI  - Adding up the evidence: systematic reviews and meta-analyses.
AB  - A systematic review aims to synthesize all available individual studies on a
      certain topic and uses explicit and reproducible methods for searching the
      literature, while a meta-analysis is a mathematical synthesis of the results of
      these individual studies. Because of the explosion of information in the
      scientific literature, these study designs can be useful tools to summarize the
      knowledge on a particular subject. In addition, combining individual studies in a
      meta-analysis increases statistical power, resulting in more precise effect
      estimates. Even though all parts of the specific methodology of systematic
      reviews include steps to minimize bias, both investigators and readers should be
      aware of potential biases like poor study quality and heterogeneity between
      studies. This paper explains how systematic reviews and meta-analyses should be
      performed and how to critically appraise them, based on an example from the
      nephrology literature.

PMID- 22135791
TI  - Control of blood pressure in chronic kidney disease: how low to go?
AB  - Blood pressure (BP) lowering is an important therapeutic goal in patients with
      diabetic and non-diabetic chronic kidney disease (CKD) for slowing progression
      and preventing onset of cardiovascular disease. The guidelines for treatment of
      hypertension in patients with CKD recommend a target BP <130/80 mm Hg, with no
      clear threshold on the lower limit. However, results of recent randomized
      controlled trials on CKD indicate that aggressive lowering of BP may not provide
      additional benefit in the vast majority of patients. This paper will review the
      literature on the main trials examining the question concerning the optimal level
      of target BP in patients with CKD and also discuss reasonable target BP levels in
      light of the evidence, as well as future direction for research in such patients.

PMID- 22135792
TI  - Management of acute coronary syndrome in patients with chronic kidney disease: if
      we don't risk anything, we risk even more.
AB  - The utilization of coronary angiography and percutaneous coronary intervention in
      the routine care for patients with acute coronary syndromes (ACS) has resulted in
      significant improvement in their prognosis. Consequently, recommendations on the
      use of these management strategies are reflected in the ACC/AHA guidelines for
      the management of patients with unstable angina and myocardial infarction.
      However, among other causes, the 'phobia' of nephrotoxicity of iodinated contrast
      media (ICM) in chronic kidney disease (CKD) patients and its claimed adverse
      effect on short-term and long-term survival has led to a worryingly low use of
      ICM-based diagnostic and therapeutic interventions in patients with CKD. We argue
      that the fear of iodinated contrast media-induced acute kidney injury (ICI-AKI)
      is not a valid reason to avoid ICM-based investigations/interventions in CKD
      patients with ACS; the risks of myocardial infarction and death greatly outweigh
      the risk of ICI-AKI in most of these patients and hence they should always be
      considered for myocardial revascularization.

PMID- 22135793
TI  - Renal involvement in psychological eating disorders.
AB  - Psychological eating disorders--anorexia nervosa (AN), bulimia nervosa (BN),
      binge eating disorder--are an increasing public health problem with severe
      clinical manifestations: hypothermia, hypotension, electrolyte imbalance,
      endocrine disorders and kidney failure; they are of interest to nephrologists,
      but pathophysiological mechanisms in determining the renal involvement are still
      unclear. We describe pathophysiology, histological features and clinical
      manifestations of the most frequent psychological eating disorders: AN and BN.
      Regarding AN, we analyze the recent literature, and identify 3 principal pathways
      towards renal involvement: chronic dehydration-hypokalemia, nephrocalcinosis and
      chronic rhabdomyolysis. Regarding BN, we describe the correlation between obesity
      and many proinflammatory cytokines, chemokines, growth factors and adipokines,
      having potential metabolic and hemodynamic effects on the kidney and an important
      role in the pathogenesis of obesity-related renal injury, independently of
      hypertension and diabetes.

PMID- 22135794
TI  - Prognostic value of standard parameters as predictors for long-term renal
      replacement therapy after liver transplantation.
AB  - Chronic kidney disease has become increasingly prevalent after liver
      transplantation (LTPL) because outcome and survival rates have improved. Chronic
      kidney insufficiency is most likely associated with increased morbidity and
      mortality. The challenge is to identify patients who will be in need of long-term
      renal replacement therapy (RRT) after LTPL. We analyzed 208 liver transplant
      recipients with respect to mortality, associated laboratory values, underlying
      liver disease, immunosuppressive protocol and the need for RRT. Long-term RRT was
      defined by the need for RRT 3 months after LTPL. Altogether, 5.8% of the
      surviving study patients remained in need of RRT 3 months after LTPL. All of
      these patients continued to need RRT throughout the study period (2 years). The
      need for RRT significantly increased the 2-year mortality rate 4.3-fold, from
      15.4 to 66.7% (p = 0.004). Comparison of laboratory and clinical parameters at
      the time of LTPL revealed no significant differences for creatinine, albumin and
      MDRD between patients undergoing hemodialysis 3 months after LTPL and patients
      without RRT. Comparing mean urea, a difference was observed. However,
      multivariate regression analyses using easy-to-observe demographic or laboratory
      parameters failed to generate a model to predict the need for RRT after LTPL. In
      addition, a comparison of underlying liver disease and immunosuppressive regimes
      identified no significant differences. Taken together, patients who were on
      hemodialysis 3 months after LTPL were also on hemodialysis 2 years after LTPL or
      until death. RRT 3 months after LTPL may predict the risk for chronic renal
      insufficiency and is associated with significantly increased mortality.

PMID- 22135796
TI  - Single-cell analysis: Imaging is everything .

PMID- 22135795
TI  - Stopping renin-angiotensin system inhibitors in chronic kidney disease:
      predictors of response.
AB  - BACKGROUND/AIMS: Renin-angiotensin system (RAS) inhibitors are considered first
      line agents for hypertensive patients with progressive chronic kidney disease
      (CKD). In a previous study, we showed that stopping RAS inhibitors increased
      estimated glomerular filtration rate (eGFR) in a significant number of advanced
      CKD patients. The present study tries to address who would benefit and whether
      this benefit is predictable. METHODS: Forty-three CKD stage 4 patients had RAS
      inhibitors stopped and were followed for at least 24 months. Compared outcome
      groups were 'alive', 'renal replacement therapy (RRT)' or 'died'. Improvement in
      eGFR was used in a receiver-operating characteristic curve and finds the best
      predictor for surviving without RRT. RESULTS: Patients who survived without RRT
      were all hypertensive and had a higher eGFR increment after stopping the drugs.
      Those with eGFR improvement >=5 ml/min/1.73 m(2) were the most likely to survive
      long term without RRT (log-rank test, p = 0.03). They had a significant increment
      in blood pressure that correlated with eGFR improvement (r = 0.403, p = 0.013).
      CONCLUSION: A significant increase in eGFR after stopping RAS inhibitors suggests
      that long-term survival without RRT is more likely. Our findings question the
      universal preemptive indication of RAS inhibitors in advanced CKD and suggest
      that they can be safely stopped, at least in some patients.

PMID- 22135797
TI  - Health of the Public: publication rate following program structure modification.

PMID- 22135798
TI  - Relationships between the stereochemistry and biological activity of fungal
      phytotoxins.
AB  - Toxins produced by phytopathogenic fungi assume great importance because of their
      involvement in several plant diseases. Although such pathogens are known to have
      seriously damaged crops, forest, and environmental resources, they represent a
      very important tool to develop new environmentally friendly herbicides and
      fungicides. This review deals with the relationships between the biological
      activity of some phytotoxins produced by pathogenic fungi for major forest plants
      and for damaging weeds and their stereochemistry. In particular, the methods used
      to determine their relative and/or absolute configuration will be illustrated.
      These include the application of Mosher's and Murata's methods, X-ray
      diffractometric analysis, circular dichroism, and the use of computational
      methods to determine the theoretical optical rotatory power as well as the CD
      spectrum. The importance of determining the absolute configuration to achieve the
      total synthesis of some phytotoxins, interesting for their potential practical
      application, is also discussed.

PMID- 22135799
TI  - Role of polyproline II conformation in human tropoelastin structure.
AB  - In this review, we present a comprehensive overview of the molecular studies on
      human tropoelastin domains accomplished by Tamburro and co-workers in the last
      decade. The used approach is the reductionist approach applied to human
      tropoelastin and is based on the observation that the tropoelastin gene exhibits
      a cassette-like organization, with a regular alternation of cross-linking and
      hydrophobic domains putatively responsible for the elasticity of the protein. The
      peculiar structure of human tropoelastin gene prompted us to study the isolated
      domains encoded by the exons of tropoelastin, with the perspective to get deep
      insights into the structural properties of the whole protein. At the molecular
      level, the results clearly evidence large flexibility of the polypeptide chains
      in the hydrophobic domains, which oscillate between rather extended and folded
      conformations. An important role was assigned to poly-proline II conformation
      considered as the hinge structure in the dynamic conformational equilibrium
      suggested for the hydrophobic domains. For the lysine-rich cross-linking domains,
      the structural studies exactly localized alpha-helix along the polypeptide
      sequence. Furthermore, at supramolecular level, these studies showed that several
      domains are able to self-assemble in two different aggregation patterns, the
      fibrous elastin-like structure for some proline-rich hydrophobic domains and the
      amyloid-like for some glycine-rich hydrophobic domains. Accordingly, the studies
      suggest that the reductionist approach was a valid tool for studying a complex
      protein, such as elastin, elucidating not only the structure but also the
      specific role played by its constituent domains.

PMID- 22135800
TI  - Experimental methods for measuring optical rotatory dispersion: survey and
      outlook.
AB  - The measurement of optical rotation (OR) and optical rotatory dispersion has been
      finding renewed interest for some years, because of advancement in computational
      methods and in the performance of new experiments. Here, we shortly review the
      traditional and most-used experimental methods. We define and discuss the two
      main types of approaches in measuring OR: the intensity method and the optical
      null method. We report on some new results obtained by redesigning experiments
      based on the first approach, by adapting nonsophisticated hardware to current
      circular dichroism instrumentation.

PMID- 22135801
TI  - Modeling solvent effects on chiroptical properties.
AB  - In this article, the most advanced extensions of solvation models to chiroptical
      properties of solvated systems will be reviewed. The main aspects determining the
      complex phenomenon of solvation will be first discussed in terms of the physical
      interactions beyond them and successively translated in a computational language
      introducing the specific models. A particular attention will be devoted to the
      family of solvation models which couple a quantum-mechanical description of the
      molecular solute and a continuum description of the solvent. The theoretical
      analysis will be supported with examples of applications showing the
      potentialities of the models and their accuracy in capturing the essence of
      solvent effects on optically active molecules.

PMID- 22135802
TI  - Central-to-axial chirality transfer revealed by liquid crystals: a combined
      experimental and computational approach for the determination of absolute
      configuration of carboxylic acids with an alpha chirality centre.
AB  - The conversion into 6,7-dihydro-5H-dibenz[c,e]azepine (DAZ) N-protected amides is
      a viable route for the determination of the absolute configuration of chiral 2
      substituted carboxylic acids. The biphenyl moiety of DAZ, besides being a probe
      of chirality for the electronic circular dichroism (ECD) spectroscopy, makes
      these systems suitable for configuration assignment by exploiting the chirality
      amplification which occurs in nematic liquid crystals. To assess the reliability
      of the liquid crystal method in detecting the absolute stereochemistry of chiral
      amides bound to a biphenyl group, we measured the helical twisting power of a
      series of DAZ-N-protected amides and compared these data with the results
      obtained from ECD measurements. We will show that the liquid crystal method,
      corroborated by HTP predictions, is trustworthy with our biphenyl derivatives,
      even when ECD spectra are ambiguous for the presence of aryl moieties displaying
      strong UV absorptions in the same range of the biphenyl chromophore.

PMID- 22135803
TI  - Refined model of optical activity of cis-dihydrodiol metabolites: role of 1,3
      diene conformation in the electronic circular dichroism spectra.
AB  - The effect of the secondary structural feature, that is, nonplanarity of carbon
      carbon double bonds, on the rotatory strength of the long-wavelength pi-pi*
      electronic transition has been investigated for the series of monocyclic cis
      dihydrodiol arene metabolites and model compounds. The contribution from
      nonplanar C=C bonds to the overall rotatory strength of the pi-pi* electronic
      transition is more significant than the contribution from twisted 1,3-diene
      chromophore. The effect of the substitution pattern in the cyclohexadiene
      skeleton may be decisive for the sign of the long-wavelength pi-pi* Cotton
      effect.

PMID- 22135804
TI  - Searching for a good candidate to perform a chiral nuclear magnetic resonance
      experiment in disordered phase: a study of 8,9-difluoro-P-hexahelicene.
AB  - Calculations of nuclear magnetic shielding polarizabilities of the P-hexahelicene
      and 8,9-difluoro-P-hexahelicene molecules have been accomplished at the CTOCD
      DZ2/6-31G(d,p) level. Pseudoscalars of the nuclear magnetic shielding
      polarizability are the largest reported so far for second-row atoms. The rf
      voltage generated by the rotating chiral electric polarization, induced by the
      permanent magnetic dipole moment of the (19)F nuclei of the 8,9-difluoro-P
      hexahelicene and by the spectrometer's magnetic field, is predicted to be ~10 nV,
      that is, detectable with modern equipments.

PMID- 22135805
TI  - The critical main-chain length for helix formation in water: determined in a
      peptide series with alternating Aib and Ala residues exclusively and detected
      with ECD spectroscopy.
AB  - Critical main-chain length for peptide helix formation in the crystal (solid)
      state and in organic solvents has been already reported. In this short
      communication, we describe our results aiming at assessing the aforementioned
      parameter in water solution. To this goal, we synthesized step-by-step by
      solution procedures a complete series of N-terminally acetylated, C-terminally
      methoxylated oligopeptides, characterized only by alternating Aib and Ala
      residues, from the dimer to the nonamer level. All these compounds were
      investigated by electronic circular dichroism in the far-UV region in water
      solution as a function of chemical structure, namely presence/absence of an ester
      moiety or a negative charge at the C-terminus, and temperature. We find that the
      critical main-chain lengths for 3(10)- and alpha-helices, although still formed
      to a limited extent, in aqueous solution are six and eight residues,
      respectively.

PMID- 22135806
TI  - Asymmetric addition of dimethylzinc to alkylidenmalonates mediated by phosphorous
      ligands: a new synthetic route to floral fragrances.
AB  - Six new phosphite ligands were prepared and their efficiency as chiral ligands
      was investigated in the copper-catalyzed asymmetric conjugate addition of
      dimethylzinc to diethyl 3-phenylpropylidenmalonate (5), affording the addition
      product with ees up to 74%. Moreover, a simple and straightforward route to
      floral fragrances Phenoxanol, Citralis, and Nitrile Citralis in optically active
      form through the above cited reaction was proposed.

PMID- 22135808
TI  - Mono- and bis-quinidine organocatalysts in the asymmetric methanolysis of cis
      1,2,3,6-tetrahydrophthalic anhydride: a conformational and mechanistic NMR study.
AB  - The enantioselective organocatalytic methanolysis of cis-1,2,3,6
      tetrahydrophthalic anhydride mediated by quinidine derivatives with pyridazine or
      anthraquinone core was investigated, carrying out a detailed nuclear magnetic
      resonance study of the conformational preferences of the alkaloid catalysts in
      the pure solvent and in the presence of the reaction substrates and products. No
      significant interaction between the meso-anhydride and the alkaloid derivatives
      was detected. In contrast, evidence for a considerable influence of the alcohol
      reactant on the conformational state of some of the chiral organocatalysts could
      be obtained, which lends support to the hypothesis of general-base catalysis
      mechanism, as opposed to the nuclephilic one. The catalytic properties of the
      studied derivatives showed no obvious correlation with their conformational
      prevalence in the resting state, suggesting that the alkaloid 9-O substituent
      should have a more active role than merely enforcing the chiral fragments to
      adopt a preferential reactive conformation. A strong enantioselective interaction
      between the enantiomers of the hemiester product and the alkaloid derivatives was
      also observed, leading to the conclusion that in the actual reaction conditions a
      relatively large fraction of the latter is in the protonated form.

PMID- 22135807
TI  - An alternative stereoselective synthesis of (R)- and (S)-Rosaphen(r) via
      asymmetric catalytic hydrogenation.
AB  - We report an alternative synthesis of the two enantiomers of the floral fragrance
      Rosaphen(r). The key intermediate 2-methyl-5-phenylpentanoic acid 3 is
      synthesized via asymmetric hydrogenation (ee up to 99%) in the presence of an in
      situ prepared ruthenium catalyst containing the chiral ferrocenyl phosphine
      Mandyphos-4.

PMID- 22135809
TI  - Enantiopure Ti(IV) amino triphenolate complexes as NMR chiral solvating agents.
AB  - Enantiopure Ti(IV) complexes bearing pseudo-C(3) amino triphenolate ligands have
      been synthesized and characterized. The complexes bearing ortho phenyl groups act
      as (1)H NMR chiral solvating agent (CSA) for the stereochemical analysis of a
      series of sulfoxides. The coordination of a Lewis base coligand (sulfoxide) and
      the presence of aromatic rings are the key structural factors for the efficiency
      of the CSA.

PMID- 22135810
TI  - Comparison of mid-infrared Fourier transform vibrational circular dichroism
      measurements with single and dual polarization modulations.
AB  - Fourier transform infrared vibrational circular dichroism (FTIR-VCD) measurements
      have gone through major advances in the last decade. A major thrust in these
      advances was to find ways that can minimize the VCD spectral artifacts and obtain
      the VCD signals at enhanced signal quality. However, all these advances are not
      incorporated in FTIR-VCD instruments manufactured by some commercial
      manufacturers. In this article, we compare the measurements obtained with single
      and dual polarization modulations to seek the attention of the users of single
      polarization modulation method in minimizing the artifacts in such measurements.
      We also report that the VCD spectrum of a home-made collagen film can serve as a
      simple and convenient sample for routine verification of the correct functioning
      of the VCD spectrometers.

PMID- 22135811
TI  - Stereodivergent synthesis of diastereoisomeric carba analogs of glycal-derived
      vinyl epoxides: a new access to carbasugars.
AB  - A convenient method for the stereoselective synthesis of diasteroisomeric vinyl
      epoxides (-)-2alpha and (-)-2beta, the carba analogs of D-galactal and D-allal
      derived vinyl epoxides 1alpha and 1beta, has been elaborated starting from tri-O
      acetyl-D-glucal. The key step of this synthesis is an application of the known
      Claisen thermal rearrangement of a glucal derivative, the vinyl allyl ether (+)
      3b, which allows to switch the glycal structure into the corresponding carba
      analog scaffold. Epoxides (-)-2alpha and (-)-2beta derive from the same synthetic
      intermediate, the trans diol (+)-5.

PMID- 22135812
TI  - Evidence-based guideline update: plasmapheresis in neurologic disorders.

PMID- 22135813
TI  - Evidence-based guideline update: plasmapheresis in neurologic disorders.

PMID- 22135814
TI  - Evidence-based guideline update: plasmapheresis in neurologic disorders.

PMID- 22135815
TI  - Evidence-based guideline update: plasmapheresis in neurologic disorders.

PMID- 22135816
TI  - Evidence-based guideline update: plasmapheresis in neurologic disorders.

PMID- 22135817
TI  - Evidence-based guideline update: plasmapheresis in neurologic disorders.

PMID- 22135818
TI  - Evidence-based guideline update: plasmapheresis in neurologic disorders.

PMID- 22135819
TI  - Cell phone photos tested for use in medication adherence to treat meth addiction.

PMID- 22135820
TI  - Join the campaign to fight dementia.

PMID- 22135821
TI  - Assess your health for Mental Health Week.

PMID- 22135822
TI  - Sleep and transcultural CPE coming your way.

PMID- 22135823
TI  - Diagnostic discussion. Primary herpes.

PMID- 22135824
TI  - Commentary.  Dr. Aaron T. Beck's enduring impact on mental health.

PMID- 22135825
TI  - Aspirin and cancer: will a tablet a day keep tumors at bay?

PMID- 22135826
TI  - Reducing prostate cancer risk: good news, bad news, or no new news?

PMID- 22135827
TI  - On call. My doctor just started me on Zocor to lower my cholesterol. I have had
      just one side effect, forgetfulness. It's not as bad as it sounds, since my
      memory remains excellent, except that I often forget to take my pill in the
      evening. So I'd like to know if it would be okay for me to take Zocor in the
      morning with my other pills, which I never forget.

PMID- 22135828
TI  - On call.  I am a 64-year-old man.  Aside from diabetes, I've been healthy and
      until now, the only prescription I've taken is insulin.  But I've been having
      trouble with erections, and my doctor just gave me a prescription for Viagra.  He
      also told me to be careful about using other drugs with Viagra but didn't give me
      a list.  Can you please fill me in?

PMID- 22135829
TI  - Intraoperative CT: A teaching tool for the management of complex facial fracture
      fixation in surgical training.

PMID- 22135830
TI  - The University of North Dakota (SCORE) experience.

PMID- 22135831
TI  - Legacy institute for surgical education and innovation: current progress and
      future direction.

PMID- 22135832
TI  - Acetylcholine activates a chloride channel as well as glutamate and GABA.
AB  - In conventional two microelectrode experiments,acetylcholine had qualitatively
      the same effect as GABA and glutamate on membrane potential and input resistance
      of muscle fibres of the opener and intrinsic stomach muscles of
      crayfish(Austropotamobius torrentium). In patch-clamp experiments,acetylcholine
      occasionally elicited single channel openings in cell-attached patches on these
      muscles. If outside-out patches were excised and the C1(-) (-)concentration was
      high on both sides of the membrane, acetylcholine at concentrations of1 nM
      regularly elicited single channel currents. The amplitude of single channel
      currents depended strongly on the intracellular concentration of C1(-).The
      reversal potential of the channel, determined after replacing intracellular K (+)
      with Cs (+), corresponded to the Nernst potential for C1(-). The voltage
      dependence and the reversal potential of single channel current amplitudes
      elicited by ACh, glutamate and GABA were identical. The distribution of life
      times of openings (> 1 ms) elicited by ACh and glutamate could be fitted by a
      single exponential with a time constant of about 2.5 ms, corresponding to the
      mean open time. ACh and glutamate applied to the same outside-out patch showed
      cross-desensitization, and thus ACh and glutamate activate the same channels. An
      excitatory, cationic ACh-activated channel could not be identified.Permeabilities
      of the chloride channel were calculated according to the Goldman-Hodgkin-Katz
      equation at different membrane potentials. Negative single channel current
      amplitudes (inward currents)could be fitted with a permeability of (pi)(2) =3.9 x
      l0 (-14) (cm3s)(-1). For positive currents (outward)the channel had a
      permeability of (pi)1 = 1.4 x10(-14) (cm3s)(-1). The permeability of the channel
      declined from 16 x 10 (-14) (cm3s)(-1) to 2.3 x 10 (-14) cm3s)(-1) if the
      intracellular C1(-) (-)concentration was raised from 6 to 257 mM. The activation
      elicited by acetylcholine was inhibited by extracellular Ca (+)(+). The mean
      current activated by ACh was reduced by a factor of 50 if the extracellular
      concentration of Ca (+)(+) was raised from 0.1 mM to the physiological
      concentration of 13.5 mM.

PMID- 22135833
TI  - The evolution of Mayo Clinic Proceedings.

PMID- 22135834
TI  - Mayo Clinic Proceedings 2002: new activities, new services.

PMID- 22135835
TI  - Mayo Clinic Proceedings 2004: A view of the present, a peek at the future.

PMID- 22135836
TI  - Mayo Clinic Proceedings 2007: Enriching our service to authors and readers.

PMID- 22135837
TI  - The insecticide avermectin b (la) activates a chloride channel in crayfish muscle
      membrane.
AB  - Effects of avermectin Bl a (AVM) have been tested on excised outside-out or
      inside-out patches of crayfish stomach muscle membrane. Continuous supervision of
      AVM (0.1-1 pmoll (-1)) to the outside-out patches induced openings of channels(22
      pS) which were similar in conductance and kinetics to the chloride channels
      activated by glutamate, quisqualic acid, ibotenic acid and nicotinic
      agonists,whereas GAB A mainly activated a second, larger conductance state (44
      pS). This effect was reversible. AVM did not activate the excitatory, glutamate
      activated cation channel. Upon raising the AVM-concentration to 10 pmol1(-1) and
      above, an enormous increase in the rate of openings of channels (22 pS) occurred.
      This effect could not be washed out during the lifetime of the patch. Using
      inside-out patches,it was shown that the single-channel current amplitude, for
      both the reversible and irreversible drug actions, strongly depended on
      intracellular chloride concentration.Applied to the sarcoplasmic side of inside
      out patches, AVM did not activate any channel. The distribution of open times for
      0-1 pmol1(-1) AVM could be fitted by a single exponential ((tau)=3-3 ms). For a
      higher AVM concentration(1 pmol1(-1)) two exponentials ((tau)(1) = 0-5 ms,
      (tau)(2) = 2-4 ms) were needed to fit the distribution. A similar effect was
      elicited by decreasing the extracellular Ca2(+)concentration from 13-5 to 1
      mmol1(-1) during the application of 0.1 pmol1(-1) AVM.Picrotoxin blocked the
      activation of chloride channels for both the reversible and irreversible effects
      of AVM. It is suggested that AVM activates the multi transmitter-gated chloride
      channel in this preparation. Binding sites for the drug are discussed.

PMID- 22135838
TI  - The diagnosis of art: melancholy and the portrait of Dr. Gachet.

PMID- 22135839
TI  - The diagnosis of art: diastrophic dysplasia and Hephaistos.

PMID- 22135840
TI  - The diagnosis of art: Lowry's cripples.

PMID- 22135842
TI  - The diagnosis of art: Millais' blind girl.

PMID- 22135841
TI  - The diagnosis of art: Albrecht Durer and the Christ Child's drooped shoulder.

PMID- 22135844
TI  - [Social factors that determines health (5) WHO policies dealing with disparity in
      health].

PMID- 22135845
TI  - [Health service research (12) Incorporation of the ideal of the International
      Classification of Functioning into facility care--through the preparation of the
      "R4 System" assessment format].

PMID- 22135843
TI  - Communicating about alcohol consumption to nonharmful drinkers with Hepatitis C:
      patient and provider perspectives.
AB  - BACKGROUND: Abstaining from alcohol consumption is generally recommended for
      patients with Hepatitis C(HCV). However, mixed research findings coupled with a
      lack of consistent guidelines on alcohol consumption and HCV may influence what
      healthcare providers tell their HCV patients about drinking. This may be more
      problematic when advising nonharmful drinkers with HCV, a population for whom
      consumption would not bea problem in the absence of their HCV diagnosis.
      OBJECTIVE: This study explores what healthcare providers advise their HCV
      patients who are drinking alcohol at nonharmful levels about alcohol use and what
      these patients actually hear. DESIGN: We conducted separate focus groups and
      interviews about alcohol use and HCV with nonharmful drinkers with HCV (N=50) and
      healthcare providers (N=14) at a metropolitan teaching hospital. All focus groups
      and interviews were audio-taped, transcribed, and analyzed using NVivo, a
      qualitative data management and analysis program. RESULTS: We found similar
      themes about HCV and alcohol consumption (stop completely, occasional drink is
      ok, cut down, and provision of mixed/ambiguous messages), reported by both
      providers and patients.Patient respondents who reported hearing "stop
      completely"were more likely to have had their last medical visit at the
      gastroenterology (GI) clinic as opposed to the internal medicine (IM) clinic.
      Furthermore, IM providers were more likely to give their recommendations
      in"medical language" than were GI providers. CONCLUSIONS: To make the best health
      related decisions about their disease, HCV patients need consistent information
      about alcohol consumption. Departments of Internal Medicine can increase provider
      knowledge about HCV and alcohol use by providing more education and training on
      HCV.

PMID- 22135846
TI  - [Public health for scientific analysis of society and health (8) "Medical cost of
      the aged"].

PMID- 22135847
TI  - [Public health monitoring report (5) "Health status disparity among the aged
      according to their social status"].

PMID- 22135848
TI  - Biochemia Medica introduces the revised policy on statement of conflict of
      Interest.
AB  - Biochemia Medica announces that from this issue Journal will be publishing the
      Statement on Conflict of Interest for Authors for all article types in printed as
      well as in electronic form of the Journal. This way Journal wishes to provide its
      readers the opportunity to unambiguously judge the quality and reliability of the
      data presentation and potential competing interests that could have biased the
      quality of the presented work in any way. This decision was made because we
      believe that scientific journals have an ultimate responsibility to provide
      unbiased scientific articles to its readership. We also believe that if any
      potential source of bias exists, it is the responsibility of the journal to
      disclose this information, since this might influence the judging the manuscript
      by editors, reviewers and readers. Therefore, when submitting their work in the
      future, author are kindly invited to make sure that they have carefully
      considered and disclosed all potential sources of competing interests that might
      have influenced their work. We hope that in such way we can help build a better
      future for the evidence based scientific research, on an international level.

PMID- 22135849
TI  - Summarizing and presenting numerical data.
AB  - Scientific hypothesis and type of the study define variables that have to be
      measured. Measurements are determined by four distinct scales of measurement;
      nominal, ordinal, interval and ratio, producing two distinct types of data:
      categorical and numerical. Numerical data are usually summarized and presented by
      distribution, measures of central tendency and dispersion. For normally
      distributed data, arithmetic mean and standard deviation are used. For data not
      normally distributed, median with data range (minimum to maximum, interquartile
      range or percentile range) and mode are used. Commonly used graph types in
      descriptive statistics for numerical data presentation are error bar and box-and
      whisker plots. Outliers are values that are numerically distant from the rest of
      the data and must be recognized.

PMID- 22135850
TI  - Eosinophil cationic protein--current concepts and controversies.
AB  - Eosinophil cationic protein (ECP) is a heterogeneous molecule originating from
      activated eosinophil granulocytes. Biological activity and the cellular content
      of ECP are determined by genetic and posttranslational factors. Several single
      nucleotide polymorphisms (SNPs) in human ECP gene (RNASE3) have been described so
      far. ECP is a mediator in host immune response to parasites, bacteria and
      viruses. By its cytotoxic and non-cytotoxic activity, ECP may also cause side
      effects in the host's own tissues. The largest number of clinical studies is
      focused on the role of ECP in eosinophil-related disorders, particularly in
      asthma. Although present in numerous body fluids, difficult bioavailability of
      biological material, invasive sampling methods and complex sample management
      prior to ECP level determination are the reasons that serum is most commonly used
      in routine laboratory practice. As numerous biological and methodological
      preanalytical factors (the type of collection test-tube, temperature and duration
      of blood clotting, centrifugation, hemolysis) may affect test result, the sample
      for serum ECP determination should be collected under standardized conditions.
      Regarding interpretation of results, it is necessary, along with absolute ECP
      concentration values, to monitor changes in ECP concentration during the duration
      of disease or after implemented therapy, and interpret ECP test result in
      combination with other laboratory and clinical findings. Rational approach to
      selection of new tests is indeed one of important requirements that medical
      workers meet today. To enable them to determine the clinical significance of ECP
      with better certainty, further studies on a large number of specific patient
      groups are needed.

PMID- 22135851
TI  - The paraoxonase 1, 2 and 3 in humans.
AB  - The paraoxonase gene family in humans includes three members: PON1, PON2 and
      PON3. The products of those three genes are the following enzymes: paraoxonase 1
      (PON1), paraoxonase 2 (PON2) and paraoxonase 3 (PON3). PON1 is mainly associated
      with a high density lipoprotein (HDL). A small amount of this enzyme is also
      bound to very low-density lipoprotein (VLDL) and postprandial chylomicrons. PON1
      possess organophosphatase, arylesterase and lactonase activity and it hydrolyzes
      many different substrates. It is also known that PON1 may have antiatherogenic
      function. Compared to the PON1, PON2 and PON3 are much less studied and
      described. PON2 is ubiquitously expressed intracellular protein, while PON3 is
      bound to HDL, like PON1. The both enzymes possess antioxidant properties.

PMID- 22135852
TI  - Interleukin 13 expression in the primary breast cancer tumour tissue.
AB  - INTRODUCTION: The aim of this study was to investigate the presence and the
      expression levels of the interleukin 13 (I1-13) in the primary breast cancer
      tumour tissue in relation to the unchanged breast tissue in the same patients and
      to the breast tissue in the patients with benign breast disease, and to
      investigate the correlation between the IL-13 expression levels and the
      pathohistological factors, and between IL-13 expression and estrogens and
      progesterone receptor status. MATERIALS AND METHODS: 50 patients with invasive
      ductal breast cancer and 20 patients with benign breast diseases were included in
      this prospective case-control study. The three-step immunohistochemical staining
      was used for testing the levels of IL-13 expression and hormone receptor status.
      RESULTS: IL-13 was present in breast cancer tumour tissue, and in the surrounding
      unchanged tissue in the same patients, and in breast tissue in patients with
      benign breast disease. The expression of IL-13 was significantly higher in breast
      cancer tumour compared with surrounding tissue (P < 0.05) of the same, lymph node
      positive patients. In addition, IL-13 expression was significantly higher in
      breast cancer tumour compared with breast tissue in patients with benign breast
      diseases (P < 0.01). There was significant correlation between IL-13 expression
      and tumour size in patients with lymph node-negative breast cancer (r = 0.405, P
      = 0.050). There was no significant correlation between IL-13 expression and the
      other pathohistological factors, and no significant correlation between IL-13
      expression and the lymph node status. CONCLUSION: Obtained results suggest
      possible involvement of IL-13 in breast carcinogenesis.

PMID- 22135853
TI  - Urates in exhaled breath condensate of children with obstructive sleep apnea.
AB  - BACKGROUND: Urate levels may be a marker of oxidative stress. The aim of the
      present study was to find out are there any differences in urate concentrations
      in exhaled breath condensate (EBC) between children with obstructive sleep apnea
      (OSA) and healthy children. MATERIALS AND METHODS: EBC was collected in children
      with obstructive sleep apnea (OSA) and clinically healthy children. Urate
      measurements in EBC and serum were performed by enzymatic color test. RESULTS:
      The higher concentration of urates in EBC of children with OSA than clinically
      healthy children indicate the oxidative stress in their airways. Since there was
      no significant difference in serum concentration of urates between children with
      OSA and healthy children, it could be considered that urates are sintetized in
      the airways of children with OSA. CONCLUSIONS: The present study indicated that
      urates in EBC (but not in serum) may be used as a marker of local synthesis of
      antioxidant compounds, but definitive conclusion must be supported by
      investigations involving larger number of participants.

PMID- 22135854
TI  - Impaired oxidative balance and association of blood glucose, insulin and HOMA-IR
      index in migraine.
AB  - INTRODUCTION: The nature of the relationship between glucose metabolism and
      occurrence of migraine has not been elucidated precisely. This study investigated
      the status of oxidative/antioxidative balance and its relationship with the
      glucose metabolism in migraineurs to get new points of view for the underlying
      oxidative mechanisms. MATERIALS AND METHODS: Sixty migraineurs and 46 control
      subjects were included in the study. Oxidative stress index, total oxidant and
      antioxidant status of both groups were examined in addition to the insulin and
      HOMA-IR index levels. RESULTS: HOMA-IR index was significantly enhanced in
      migraineurs (P = 0.038); similarly oxidative stress index and total oxidant
      status were higher in patients compared to the controls (P < 0.001 for both).
      CONCLUSION: This preliminary study shows that oxidative/antioxidative balance
      shifts towards the oxidative status in migraine. Higher total oxidant status and
      elevated HOMA-IR index might play a role in the potential early pathogenesis for
      migraine.

PMID- 22135855
TI  - New ways to deal with known preanalytical issues: use of transilluminator instead
      of tourniquet for easing vein access and eliminating stasis on clinical
      biochemistry.
AB  - INTRODUCTION: Tourniquet due venous stasis can alter both concentration and/or
      activity of several blood analytes, but is rarely regarded as an issue of
      laboratory variability. To overcome the problem transillumination devices (TD)
      have been proposed for a stasis-free phlebotomy. In this paper the use of a TD in
      place of tourniquet during blood collection has been evaluated. MATERIALS AND
      METHODS: Blood was collected from 250 volunteers divided in five homogenous
      groups of tourniquet times (G1: 30 sec, G2: 60 sec, G3: 90 sec, G4:120 sec, G5:
      180 sec) and compared to blood obtained using TD. All samples were analyzed for
      glucose (GLU), total protein (TP), albumin (ALB), triglycerides (TRIG), potassium
      (K), sodium (NA), phosphate (PHOS), calcium (CA), alkaline phosphatase (ALKP) and
      magnesium (MG). RESULTS: In respect of TD, G1 did not show statistically
      significant increases in all clinical chemistry tests; G2 showed increases for
      GLU, TP, ALB, TRIG, K, CA, MG and ALKP. G3 and G4, showed no significant increase
      only for PHOS. G5 showed significant increases in all the tests evaluated.
      Moreover, clinically significant variations were observed for TP, ALB, K and CA
      in G2 to G5; for NA in G3 to G5; for MG in G4 and G5; for GLU, TRIG, ALKP only in
      G5. CONCLUSIONS: These results support the application of TD in blood collection
      for routine clinical chemistry laboratory tests, suggesting its use should be
      more diffused.

PMID- 22135856
TI  - Lipemia interferences in routine clinical biochemical tests.
AB  - INTRODUCTION: Lipemic specimens are a common and frequent, but yet unresolved
      problem in clinical chemistry, and may produce significant interferences in the
      analytical results of different biochemical parameters. MATERIAL AND METHODS: The
      aim of this study was to examine the effect of lipid removal using
      ultracentrifugation of lipemic samples, on some routine biochemistry parameters.
      Among all the samples obtained daily in our laboratory, the ones which were
      visibly muddy were selected and underwent to a process of ultracentrifugation,
      being determined a variety of biochemical tests before and after
      ultracentrifugation. A total of 110 samples were studied. RESULTS: We found
      significant differences in all the parameters studied except for total bilirubin,
      glucose, gamma-glutamyl transferase (GGT) and aspartate aminotransferase (AST).
      The greatest differences in the parameters analyzed were found in the
      concentration of alanine aminotransferase (ALT) (7.36%) and the smallest ones in
      the concentration of glucose (0.014%). Clinically significant interferences were
      found for phosphorus, creatinine, total protein and calcium. CONCLUSION: Lipemia
      causes clinically significant interferences for phosphorus, creatinine, total
      protein and calcium measurement and those interferences could be effectively
      removed by ultracentrifugation.

PMID- 22135857
TI  - Development of a new DHPLC assay for genotyping UGT1A (TA)n polymorphism
      associated with Gilbert's syndrome.
AB  - INTRODUCTION: Gilbert's syndrome is the most common hereditary disorder of
      bilirubin metabolism. The causative mutation in Caucasians is almost exclusively
      a (TA) dinucleotide insertion in the UGT1A1 promoter. Affected individuals are
      homozygous for the variant promoter and have 7 TA repeats instead of 6. Promoters
      with 5 and 8 TA repeats also exist but are extremely rare in Caucasians. The aim
      of our study was to develop denaturing high-performance liquid chromatography
      (DHPLC) assay for genotyping UGT1A1(TA)n polymorphism and to compare it with a
      previously described single-strand conformation polymorphism (SSCP) assay.
      MATERIALS AND METHODS: Fifty DNA samples with common genotypes ((TA)6/6, (TA)6/7,
      (TA)7/7) as well as 7 samples with one of the following rare genotypes- (TA)5/6,
      (TA)5/7, (TA)6/8 or (TA)7/8 were amplified by polymerase chain reaction (PCR) and
      genotyped by DHPLC using sizing mode. All samples were previously genotyped by
      SSCP assay which was validated by sequencing analysis. RESULTS: All samples with
      either common or rare genotypes showed completely concordant results between
      DHPLC and SSCP assays. Our results show that sizing DHPLC assay is more efficient
      compared to classical SSCP assay due to shorter time of genotyping analysis,
      ability of genotyping increased number of samples per day, higher robustness,
      reproducibility and cost-effectiveness with no loss of accuracy in detection of
      all UGT1A1(TA)n genotypes. CONCLUSIONS: We developed a new DHPLC assay which is
      suitable for accurate, automated, highthroughput, robust genotyping of all
      UGT1A1(TA)n polymorphism variants, compared to a labour intensive and time
      consuming SSCP assay.

PMID- 22135858
TI  - Identifying candidate genes for Parkinson's disease by integrative genomics
      method.
AB  - INTRODUCTION: The recent studies of Parkinson's disease (PD) indicate that
      genetics and environmental factors may play an important role in developing of
      PD. Nowadays, the cell death and cell adhesion are pathogenetic mechanisms which
      could be related with PD. On the basis of relationship of those mechanisms with
      PD, the aim of this study was to identify new candidate genes for PD by
      integration of results of transcriptomics studies and results obtained by
      Biomedical Discovery Support System (BITOLA). MATERIALS AND METHODS: For the
      detection of functional relationship between potential candidate gene and
      pathogenetic mechanisms associated with PD, we designed strategy of integration
      of results of transcriptomics studies with discovery approach in bibliographic
      data bases and BITOLA. Data of chromosome location, tissue-specific expression,
      function of potential candidate genes and their association with genetics
      disorders were obtained from Medline, Locus Link, Gene Cards and OMIM. RESULTS:
      Integration and comparison of results obtained using the BITOLA system and
      analysis of transcriptomics studies identified six genes (MAPT, UCHL1, NSF,
      CDC42, PARK2 and GFPT1) that occur simultaneously in both group of results. The
      function of genes NSF, CDC42 and GFPT1 in the pathogenesis of PD has not been
      studied yet. CONCLUSIONS: According to our result that aforementioned genes
      appeared in both groups of results and partially match the criteria set for the
      selection of candidate genes and their potential role in the development of PD,
      they should be tested by methods specifically intended for those three genes.

PMID- 22135859
TI  - Validation of methods performance for routine biochemistry analytes at Cobas 6000
      analyzer series module c501.
AB  - INTRODUCTION: Cobas 6000 (Roche, Germany) is biochemistry analyzer for
      spectrophotometric, immunoturbidimetric and ion-selective determination of
      biochemical analytes. Hereby we present analytical validation with emphasis on
      method performance judgment for routine operation. MATERIALS AND METHODS:
      Validation was made for 30 analytes (metabolites, enzymes, trace elements,
      specific proteins and electrolytes). Research included determination of within
      run (N = 20) and between-run imprecision (N = 30), inaccuracy (N = 30) and method
      comparison with routine analyzer (Beckman Coulter AU640) (N = 50). For validation
      of complete analytical process we calculated total error (TE). Results were
      judged according to quality specification criteria given by European Working
      Group. RESULTS: Within-run imprecision CVs were all below 5% except for
      cholesterol, triglycerides, IgA and IgM. Between-run CVs for all analytes were
      below 10%. Analytes that did not meet the required specifications for imprecision
      were: total protein, albumin, calcium, sodium, chloride, immunoglobulins and HDL
      cholesterol. Analytes that did not fulfill requirements for inaccuracy were:
      total protein, calcium, sodium and chloride. Analytes that deviated from quality
      specifications for total error were: total protein, albumin, calcium, sodium,
      chloride and IgM. Passing-Bablok regression analysis provided linear equation and
      95% confidence interval for intercept and slope. Complete accordance with routine
      analyzer Beckman Coulter AU640 showed small number of analytes. Other analytes
      showed small proportional and/or small constant difference and therefore need to
      be adjusted for routine operation. CONCLUSIONS: Regarding low CV values, tested
      analyzer has satisfactory accuracy and precision and is extremely stable. Except
      for analytes that are coherent on both analyzers, some analytes require
      adjustments of slope and intercept for complete accordance.

PMID- 22135860
TI  - Stunting: there is more than meets the eye.

PMID- 22135861
TI  - Development, validity and reproducibility of a food frequency questionnaire in
      pregnancy for the Universiti Sains Malaysia birth cohort study.
AB  - INTRODUCTION: This study aimed to develop and examine the validity and
      reproducibility of a semi-quantitative food frequency questionnaire (FFQ) among
      Malay pregnant women in Kelantan, Malaysia. METHODS: A total of 177 Malay
      pregnant women participated in the validation study while 85 of them participated
      in the reproducibility study which was carried out in the antenatal clinic of
      Universiti Sains Malaysia Hospital. The newly developed FFQ was validated against
      two 24-hour dietary recalls (DR). The FFQ was repeated 20 to 28 days apart.
      RESULTS: Results showed that the FFQ moderately over-estimated the nutrient and
      food intakes compared to the DR. Spearman correlation coefficients for nutrients
      ranged from 0.24 (fat) to 0.61 (calcium) and for foods, ranged from 0.13 (organ
      meats, onion and garlic) to 0.57 (malt drink). For nutrients, 72 to 85% of women
      were classified into the correct quartiles from the FFQ and the DR while for
      foods, 67 to 85% of women were classified correctly. Bland-Altman plot showed
      relatively good agreement between these two dietary methods. The intra-class
      correlation (ICC) was used to estimate reproducibility. It ranged from 0.75
      (vitamin C) to 0.94 (phosphorus) for nutrients while it ranged from 0.73
      (confectionary) to 0.96 (coffee) for foods. CONCLUSION: On average, at least 90%
      of pregnant women were correctly classified into the quartiles for nutrients and
      foods from the two sets of the FFQ. The FFQ presented acceptable reproducibility
      and appears to be a valid tool for categorising pregnant women according to
      dietary intake.

PMID- 22135862
TI  - Nutritional status of children living with HIV and receiving antiretroviral (ARV)
      medication in the Klang Valley, Malaysia.
AB  - INTRODUCTION: Nutrition and HIV are closely related. Any immune impairment as a
      result of HIV leads to malnutrition, which in turn, can also lead to reduced
      immunity, thus contributing to a more rapid progression to AIDS. METHODS: This
      cross-sectional study determined the nutritional status of children living with
      HIV and are receiving antiretroviral medication in the Klang Valley. A total of
      95 children aged one to eighteen years old were recruited between September 2008
      and February 2009. Data collected included socio-economic status, anthropometric
      measurements, dietary intake, medical history and serum levels of selected
      micronutrients specific for immunity. RESULTS: The mean age of the children was
      8.4 +/- 3.9 years and the mean duration on antiretroviral medications was 68.3 +/
      38.3 months. Anthropometric assessment found that 9.5% of the children were
      underweight and 31.6% were overweight. In contrast, 20.8% were stunted and 14.6%
      severely stunted. Biochemical indicators showed that 10.4% had deficiency in
      vitamin A while 12.5% had deficiency in selenium. Total cholesterol and HDL-C
      levels were found to be low in 30.5% and 10.5% of the children respectively.
      CONCLUSION: Dietary assessment showed almost all the children did not achieve the
      recommended energy intake for their age groups and almost half of the children
      did not achieve the RNI for selenium and vitamin A. This study provides an
      insight on the nutritional status of children living with HIV.

PMID- 22135863
TI  - Food preferences and dietary intakes of Filipino adolescents in metro Manila, the
      Philippines.
AB  - INTRODUCTION: This study examined differences in food preferences and dietary
      intake among male and female Filipino adolescents of different nutritional status
      as measured by body mass index (BMI). METHODS: One hundred and twenty 13-17-year
      olds from various schools and communities in Metro Manila, The Philippines were
      selected through quota sampling with BMI, sex and age as criteria. Data on mean
      dietary intake and food preference were collected using pretested instruments--a
      3-day food record and a food preference questionnaire, respectively. Resulting
      values were analysed using one-way ANOVA, Bonferroni test and Pearson's product
      moment and Spearman's correlation using SAS Enterprise Guide version 2. RESULTS:
      Preference for cereals prepared with added sugar or fat (p=0.21, p=.0240), and
      low fat meat (p=0.18, p=0.420) were found to be positively correlated with BMI,
      while preference for fruits that are high in vitamin A (p=-0.18, p=0.430) was
      negatively correlated with the said variable. Overweight respondents gave lower
      and significantly different preference scores to donut (p=.02780), banana cue
      (p=.0489) and mayonnaise (p=.0291). Respondents of different nutritional status
      also had statistically different intakes of fibre, calcium and phosphorus,
      corresponding with the positive correlation of fibre (p=0.25231, p=0.0054),
      calcium (p=0.2529, p=0.0134) and phosphorus (p=0.25887, p=0.0043) intake with
      BMI. With respect to sex, male respondents gave statistically higher preference
      for French fries (p=.0370), tofu (p=.0005), garlic (p=.0190) and mussels
      (p=.0023). Also, males have significantly higher intakes of energy and
      carbohydrate than female respondents. CONCLUSION: Results suggest that food
      preferences should be considered in the nutritional care management of
      malnourished adolescents.

PMID- 22135864
TI  - Assessing the resting energy expenditure of cancer patients in the Penang General
      Hospital.
AB  - INTRODUCTION: Malnutrition is common in cancer patients. Generally, it is
      believed that the resting energy expenditure (REE) is elevated in cancer patients
      and this contributes to the development of malnutrition. Thus, to be able to
      assess the REE is important in planning adequate nutrition support. METHODS: A
      cross-sectional study was carried out to assess the REE in patients with solid
      tumour (n=25), leukemia (n=25) and healthy subjects (n=50) by using the indirect
      calorimetry method under standard conditions. RESULTS: There was no significant
      difference between the measured REE among patients with solid tumour, leukemia
      and the control group (p=0.534). By contrast, there was a significant difference
      between the REE/kg FFM in solid tumour patients compared to the leukemia group
      and the healthy subjects, (p=0.049 and p=0.002). The REE derived from the Harris
      Benedict Equation was found to be significantly higher than the measured REE. The
      stress factor for patients with solid tumour was 1.35 and that for leukemia
      patients was 1.36. CONCLUSION: The REE/kg FFM in the cancer patients undergoing
      anticancer therapy appeared to be higher than expected compared to healthy
      subjects. The Harris Benedict Equation (HBE) was found to over-estimate the REE
      of cancer patients in the study. As the total energy expenditure (TEE) is
      estimated by multiplying the REE with the stress factor and physical activity
      factor, the overestimated REE from HBE will further increase the risk of
      overfeeding in this population.

PMID- 22135865
TI  - Body weight satisfaction: association with weight control practices among type 2
      diabetic patients.
AB  - INTRODUCTION: The recommendation to lose weight has been the guiding principle in
      the treatment of type 2 diabetic patients. However, to facilitate this process,
      it is vital to understand factors associated with personal feelings about body
      weight and related behaviour. METHODS: The objectives of this cross-sectional
      study were (1) to determine mean BMI and weight of satisfaction and (2) to
      measure the association between body weight satisfaction vs. sex, BMI, glycaemic
      control (as measured by Fasting Blood Glucose (FBG), and attempts to lose weight
      among type 2 diabetic patients. Descriptive statistics and non-parametric tests
      were employed (SPSS 16). A total of 67 subjects were recruited from Klinik
      Kesihatan Bandar Kuantan (age = 54.1 +/- 8.1 years; female = 62.7%; Malay =
      73.1%; overweight/obese = 62.7%) who completed a set of self-administered
      questionnaires. RESULTS: The mean BMI and weight of satisfaction were 27.9 +/-
      5.3 kg/m2 and 62.7 +/- 10.9 kg respectively. A greater proportion of women
      (65.0%) reported dissatisfaction with their body weight. Patients with higher BMI
      generally reported greater dissatisfaction with body weight compared to those
      with lesser BMI (p = 0.090). There was no significant difference in the glycaemic
      control of patients who were satisfied or dissatisfied with their weight (p =
      0.839). There was also no significant association between body weight
      satisfaction and diet (p = 0.957), physical activity (p = 0.517) or both (p =
      0.734). CONCLUSION: This study implies that body weight satisfaction alone is not
      a strong factor that may drive type 2 diabetic patients to control their body
      weight.

PMID- 22135866
TI  - Gender differences in body mass index, body weight perception and weight loss
      strategies among undergraduates in Universiti Malaysia Sarawak.
AB  - INTRODUCTION: This study was carried out among undergraduate students in
      Universiti Malaysia Sarawak with the objective of examining gender differences in
      body mass index (BMI), body weight perception, eating attitudes and weightloss
      strategies. METHODS: Subjects consisted of 600 undergraduates (300 males and 300
      females) recruited from the various faculties between September 2008 until mid
      November 2008. The Original Figure Rating Scale: Body Weight Perception, Body
      Shape Questionnaire (BSQ) and Eating Attitudes Test-26 (EAT-26) were used as
      assessment tools. RESULTS: Overall, 52.8% of students had normal BMI, with
      approximately an equal number of both sexes. More males than females were
      overweight (33.7%), while more females were underweight (25.3%). Males were more
      likely to perceive themselves as overweight, and fail to see themselves as
      underweight. More than half of the females preferred their ideal figure to be
      underweight, whereas about 30% males chose an overweight figure as their ideal
      model. Females were generally more concerned about body weight, body shape and
      eating than males. They diet more frequently, had self-induced vomiting, and used
      laxatives and exercise as their weight-loss strategies. CONCLUSION: Issues
      pertaining to body weight perception, eating attitudes and weight-loss strategies
      exist with differences among male and female undergraduates. Thus, in order to
      correct misperceptions among young adults, a more tailored intervention programme
      and more in-depth studies into the various factors involved are required.

PMID- 22135867
TI  - In vitro inhibitory potential of selected Malaysian plants against key enzymes
      involved in hyperglycemia and hypertension.
AB  - INTRODUCTION: This study was conducted to determine the inhibitory potential of
      selected Malaysian plants against key enzymes related to type 2 diabetes and
      hypertension. METHODS: The samples investigated were pucuk ubi (Manihot
      esculenta), pucuk betik (Carica papaya), ulam raja (Cosmos caudatus), pegaga
      (Centella asiatica) and kacang botol (Psophocarpus tetragonolobus). The
      inhibitory potential of hexane and dichloromethane extracts against the enzymes
      were determined by using alpha-amylase, alpha-glucosidase and angiotensin I
      converting enzyme (ACE) inhibition assay. RESULTS: In alpha-amylase inhibition
      assay, the inhibitory potential was highest in pucuk ubi for both hexane (59.22%)
      and dichloromethane extract (54.15%). Hexane extract of pucuk ubi (95.01%) and
      dichloromethane extract of kacang botol (38.94%) showed the highest inhibitory
      potential against alpha-glucosidase, while in ACE inhibition assay, the
      inhibitory potential was highest in hexane extract of pegaga (48.45%) and
      dichloromethane extract of pucuk betik (59.77%). CONCLUSION: This study suggests
      a nutraceutical potential of some of these plants for hyperglycemia and
      hypertension prevention associated with type 2 diabetes.

PMID- 22135868
TI  - Dietary practices among overweight and obese Chinese children in Kota Bharu,
      Kelantan.
AB  - INTRDUCTION: Obesity and chronic diseases have been increasing since the last few
      decades alongside rapid economic development in developed and developing
      countries. The alarming increase in the prevalence of childhood obesity had been
      shown by many epidemiological studies worldwide. The aims of this study were to
      determine the prevalence of overweight and obesity among Chinese school children
      in Kota Bharu, Kelantan, and to map the association between dietary practices and
      their nutritional status. METHODS: A cross-sectional study was conducted on 278
      school children aged 10 to 12 years old (144 boys and 134 girls) studying in a
      Chinese primary school in Kota Bharu. RESULTS: The survey revealed that while
      only 1.4% (n=4) were overweight, 23.4% (n=65) of the children were obese. A total
      of 67.7% (n=44) of the obese children were boys. The overweight and obese
      children (n=70) were compared with a randomly selected group of normal weight
      children (n=70). Dietary assessment showed that protein, fat and total calorie
      intake were significantly higher among the overweight group (p<0.05). A
      significantly higher proportion of the normal weight children (85.7%) took
      breakfast daily or at least 4 days per week compared to the overweight groups
      (59.4%) (p<0.05). CONCLUSION: The prevalence of obesity among school children in
      the study is a matter of concern. These findings may be useful in targeting
      programmes and strategies for prevention and intervention of childhood obesity.

PMID- 22135869
TI  - Sri Lankan rice mixed meals: effect on glycaemic index and contribution to daily
      dietary fibre requirement.
AB  - INTRODUCTION: The glycaemic index (GI) concept ranks starchy foods according to
      the blood glucose responses following ingestion. When considering commonly
      consumed Sri Lankan meals, only a few can be categorised as low GI. However, a
      significant negative correlation between the GI of Sri Lankan meals and fibre
      content has been observed indicating the potential to reduce the GI of meals by
      incorporating naturally occurring sources of fibre. Thus, the objective of this
      study was to study the effect of increased edible quantities of fibre on the GI
      of rice meals consumed in Sri Lanka. METHODS: Meal 1 consisted of rice with
      several meal accompaniments (lentil curry, boiled egg, coconut gravy and Centella
      asiatica (gotukola) leaves salad). Meal 2 contained similar constituents as meal
      1 and a Lasia spinosa (kohila) rhizome salad. The composition of meal 3 was
      similar to meal 2 but contained Trichosanthes cucumerina (snake gourd) salad
      instead of Lasia spinosa salad. Meal 3 contained similar fibre contents as meal 1
      and similar meal size as meal 2. The glycaemic indices of the three meals were
      determined with healthy individuals (n=10, age=20-30 yrs, BMI=24 +/- 3 kg/m2)
      using bread as the standard. RESULTS: Meals 1 and 3 contained total dietary fibre
      (TDF) contents of 15.2g. Meal 2 contained 16.3g TDF. The GI values of the three
      meals were 63 +/- 5, 57 +/- 5, 61 +/- 5 respectively and were not significantly
      different from one another (p>0.05). The GI of the rice mixed meal 2 was reduced
      by 9% when total edible dietary fibre content of the actual meal was increased by
      7.2%. CONCLUSION: The study results show that the GI of rice mixed meals may be
      reduced by including naturally occurring sources of fibre with starchy staples
      while fulfilling daily dietary fibre requirement of an adult at low cost.

PMID- 22135870
TI  - Socio-economic determinants of severe and moderate stunting among under-five
      children of rural Bangladesh.
AB  - INTRODUCTION: Malnutrition among under-five children is a chronic problem in
      developing countries. This study explores the socio-economic determinants of
      severe and moderate stunting among under-five children of rural Bangladesh.
      METHODS: The study used data from the 2007 Bangladesh Demographic and Health
      Survey. Cross-sectional and multinomial logistic regression analyses were used to
      assess the effect of the socio-demographic variables on moderate and severe
      stunting over normal among the children. RESULTS: Findings revealed that over two
      fifths of the children were stunted, of which 26.3% were moderately stunted and
      15.1% were severely stunted. The multivariate multinomial logistic regression
      analysis yielded significantly increased risk of severe stunting (OR=2.53, 95%
      CI=1.34-4.79) and moderate stunting (OR=2.37, 95% CI=1.47-3.83) over normal among
      children with a thinner mother. Region, father's education, toilet facilities,
      child's age, birth order of children and wealth index were also important
      determinants of children's nutritional status. CONCLUSION: Development and
      poverty alleviation programmes should focus on the disadvantaged rural segments
      of people to improve their nutritional status.

PMID- 22135871
TI  - Effect of trans fatty acids intake on blood lipid profile of workers in East
      Kalimantan, Indonesia.
AB  - INTRODUCTION: In experiencing epidemiologic transition, Indonesia faces emerging
      nutrition problems. METHODS: Among the dietary lifestyle changes over the years
      is the rising consumption of fats and oils, including trans fatty acids. Intake
      of these fatty acids from ruminant meats, hydrogenated vegetable oils and fried
      foods is known to have detrimental effects on serum lipoprotein cholesterol
      levels. The purpose of this study was to determine the effects of trans fatty
      acid intake on blood lipid profile. A prospective cohort study was conducted on
      388 workers at an on-shore oil company in East Kalimantan. RESULTS: The mean
      intake of trans fatty acid was 0.48% of the total dietary calories. Fried foods
      contributed most to the total trans fatty acid consumed at 0.20% of the total
      calories. Trans fatty acid intake from ruminant products, and margarine/
      hydrogenated vegetable oil products were 0.09% and 0.06% of calories,
      respectively. The high consumption of fried foods is associated with risks of
      hypertriglyceridemia (RR: 1.41, 95%CI 1.06; 1.86), high ratio of total
      cholesterol/ HDL-C (RR: 1.98, 95%CI 1.00; 3.98) and dyslipidemia (RR: 1.35, 95%CI
      1.00;1.84). Every additional one percent of saturated fatty acid intake is
      associated with an increase in trans fatty acids amounting to 0.03% of total
      calories (r = 0.320, p = 0.000). CONCLUSION: These results suggest that a
      reduction in consumption of fried foods will be of benefit as it will reduce
      intake of both saturated and trans fatty acids. Further studies are recommended
      to determine the intake of trans fatty acids and their health effects on other
      population groups in Indonesia.

PMID- 22135872
TI  - Type 2 diabetes in the sultanate of Oman.
AB  - During the past four decades, Oman has undergone a rapid socioe-conomic and
      epidemiological transition leading to a substantial reduction in the prevalence
      of various communicable diseases, including vaccine-preventable diseases. Health
      care planning together with the commitment of policy makers has been a critical
      factor in this reduction. However, with rapid social and economic growth,
      lifestyle-related non communicable diseases have emerged as new health challenges
      to the country. Diabetes and obesity are leading risks posed by the chronic
      diseases. The burden of diabetes has increased sharply in Oman over the last
      decade, rising from 8.3% in 1991 to 11.6% in 2000 among adults aged 20 years and
      older. The World Health Organization (WHO) predicted an increase of 190% in the
      number of subjects living with diabetes in Oman over the next 20 years, rising
      from 75,000 in 2000 to 217,000 in 2025. There is a lack of awareness of the major
      risk factors for diabetes mellitus in the Omani population generally. As
      education is often the most significant predictor of knowledge regarding risk
      factors, complications and the prevention of diabetes, health promotion in Oman
      is deemed critical, along with other prevention and control measures. Suitable
      prevention strategies for reducing the prevalence of diabetes in Oman are
      discussed. Recommendations are made for reforms in the current health care
      system; otherwise, diabetes will constitute a major drain on Oman's human and
      financial resources, threatening the advances in health and longevity achieved
      over the past decades.

PMID- 22135873
TI  - Medicinal mushroom Lingzhi or Reishi, Ganoderma lucidum (W.Curt.:Fr.) P. Karst.,
      beta-glucan induces Toll-like receptors and fails to induce inflammatory
      cytokines in NF-kappaB inhibitor-treated macrophages.
AB  - Beta-Glucan of medicinal Lingzhi or Reishi mushroom, Ganoderma lucidum (BGG),
      possesses immunostimulatory and anti-tumor activities. Innate immune cells are
      activated by the binding of beta-glucan to the dectin-1 receptor. The present
      study investigated the immunostimulating activities of BGG, including binding to
      dectin-1, secretion of cytokines and reactive oxygen species, and induction of
      Toll-like receptors (TLRs) in RAW264.7 mouse macrophages. Reverse transcription
      polymerase chain reaction and flow cytometry were used for the cytokine and TLR
      analyses. A mouse inflammation antibody array was used for protein-level cytokine
      analysis. BGG bound to dectin-1 and induced RAW264.7 cell secretion of several
      cytokines, including granulocyte colony-stimulating factor, interleukin (IL)-6,
      regulated upon activation normal T cell expressed and secreted (RANTES), tissue
      inhibitor of metalloproteinase-1, and tumor necrosis factor-alpha. The secretion
      of these cytokines was further increased by the addition of lipopolysaccharide
      (LPS). BGG also induced both nitric oxide and inducible nitric oxide synthase
      (iNOS). Treatment with an inhibitor of nuclear factor-kappa B (NF-kappaB) reduced
      the induction of IL-1, IL-6, and iNOS in a concentration-dependent manner.
      Expressions of TLR2, TLR4, and TLR6 were increased by BGG treatment, and addition
      of LPS induced further induction of TLR4 and TLR6. Our result indicates that BGG
      induces macrophage secretion of inflammatory cytokines, which can be potentiated
      by the presence of LPS, likely by binding to dectin-1 and TLR-2/6 receptors,
      which activate NF-kappaB and prompt the secretion of cytokines.

PMID- 22135874
TI  - 28-day oral safety evaluation of extracellular polysaccharopeptides produced in
      submerged culture from the turkey tail medicinal mushroom Trametes versicolor
      (L.:Fr.) Pilat LH-1 in mice.
AB  - Turkey tail medicinal mushroom, Trametes versicolor (TV), is a species with a
      variety of pharmacological activities. Its intracellular polysaccharopeptides are
      widely commercialized. Recently, we found a novel TV strain LH-1 in Taiwan and
      demonstrated that the extracellular polysaccharopeptide (ePSP) of LH-1 obtained
      from submerged culture exhibits significant immunomodulatory activity. In this in
      vivo study, we further evaluated the safety of orally administered LH-1 ePSP
      using both male and female ICR mice. The LH-1 ePSP was orally administered to
      mice at levels of 0 (water), 100 (low dose), 500 (medium dose), or 1000 mg/kg/day
      (high dose) for 28 days. Clinical observations, growth, food consumption,
      histopathological examination, and clinical biochemical analyses revealed no
      adverse effects of LH-1 ePSP in mice. There were no significant differences in
      the results of target organ weights, hematological analyses, and urinalysis
      examination among groups. However, male mice that ingested high doses of LH-1
      ePSP tended to have decreased lung weights and platelet numbers. In conclusion,
      the results of the present study suggested that oral administration of LH-1 ePSP
      for 28 days is accompanied by no obvious signs of toxicity. The lack of toxicity
      supports the potential use of LH-1 ePSP as a food or dietary supplement.

PMID- 22135875
TI  - Hot water extract of the sclerotium of Polyporus rhinocerus Cooke enhances the
      immune functions of murine macrophages.
AB  - Treatment of hot water extract of the sclerotium of Polyporus rhinocerus (PRW)
      with murine macrophages including RAW 264.7 cell line and primary macrophages
      (PMs) could enhance their functional activities. These include a significant up
      regulation of pinocytosis; an increase in the production of reactive oxygen
      species (ROS) and nitric oxide (NO); an increase in tumor necrosis factor alpha
      (TNF-alpha) production and inducible nitric oxide synthase (iNOS) expression in
      both RAW 264.7 cells and PMs. Cell surface receptors for yeast-derived beta
      glucan, including Dectin-1, CR3, and TLR2, were determined by flow cytometry, and
      the expression of Dectin-1+ cells on the cell surface decreased in the responses
      of PMs to PRW. PRW increased phosphorylation of IkappaBalpha, which could trigger
      the nuclear factor kappa B (NF-kappaB) signal pathway for macrophage activation
      in RAW 264.7 cells. Therefore, the immunomodulatory effect of PRW could be
      mediated by macrophage activation via the NF-kappaB signal pathway.

PMID- 22135876
TI  - Comparative study of antioxidant activities and total phenolic content of
      selected edible wild mushrooms.
AB  - The present study aims to assess the antioxidant activities (AOA) and total
      phenolic content (TPC) of water extracts of selected edible wild mushrooms:
      Pleurotus porrigens, Schizophyllum commune, Hygrocybe conica, and Lentinus
      ciliatus. The AOA were evaluated against DPPH radical and ABTS radical cation
      scavenging ability, ferric-reducing antioxidant power (FRAP) and beta-carotene
      linoleate bleaching (beta-CB) assays, and the Folin-Ciocalteu method for TPC. BHA
      was used as reference. P. porrigens showed significantly higher (p < 0.05) DPPH*
      scavenging ability (90.78 +/- 0.30%) and FRAP (6.37 +/- 0.22 mM FE/100g), while
      Sch. commune showed significantly higher (p < 0.05) ABTS*+ inhibition activity
      (94.96 +/- 0.70%) and beta-CB inhibition activity (94.18 +/- 0.17%),
      respectively. TPC was found in a descending order of P. poriggens > L. ciliatus =
      Pleurotus ostreatus (cultivated) > H. conica = Sch. commune. Positive correlation
      was observed between the AOA and TPC. When compared to BHA (2 mM), P. porrigens
      showed significantly higher (p < 0.05) DPPH* scavenging ability and reducing
      power, while Sch. commune showed comparable DPPH* scavenging ability and ABTS*+
      inhibition activity. All the mushrooms have better ABTS*+ inhibition activity
      than BHA (1 mM). The beta-CB inhibition activity of BHA was significantly higher
      than those of edible wild mushrooms. The water extracts of edible wild mushrooms
      showed potent antioxidant activities compared to BHA to a certain extent.

PMID- 22135877
TI  - Antioxidant properties of extracts of wild medicinal mushroom species from
      Croatia.
AB  - Antioxidant activity and total phenol (TP) content of methanol and water extracts
      of three wild Croatian mushroom species Auricularia auricula-judae (Bull.) Quel.,
      Sarcoscypha austriaca (Sacc.) Boud., and Strobilurus esculentus (Wulfen) Singer
      were determined and compared with the values obtained for extracts of four
      cultivated mushrooms Agaricus bisporus (J.E. Lange) Imbach (brown and white
      strains), Pleurotus ostreatus (Jacq.) P. Kumm., and Lentinus edodes (Berk.)
      Singer. Spectrophotometric determination of the TP content was performed using
      the Folin-Ciocalteu method, while antioxidant activity was measured in a reaction
      with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH assay) and ferric
      tripyridyltriazine (Fe3+-TPTZ) complex (FRAP assay). On the average, 5.8-fold
      higher TP content was observed for water in comparison to methanol extracts of
      all analyzed mushrooms. Consequently, antioxidant activity was also higher for
      water extracts, which is evident from the obtained higher values in the FRAP
      assay and lower EC50 values in the DPPH assay. Among the three tested wild
      species, the water extract of S. esculentus exhibited the highest concentration
      of TP, 8.12 mg/g gallic acid equivalents (GAE), the highest reducing power, 19.42
      mmol Fe2+/kg, and the best radical scavenging properties, EC50= 13.5 mg/mL.

PMID- 22135878
TI  - Nonvolatile taste components of culinary-medicinal maitake mushroom, Grifola
      frondosa (Dicks.:Fr.) S.F. Gray.
AB  - Culinary-medicinal maitake mushroom Grifola frondosa (Dicks.: Fr.) S.F. Gray
      mycelium was inoculated into wheat, a new product was formed after fungal
      fermentation, and its nonvolatile taste components were studied. Contents of
      crude ash, fat, fiber, and protein were higher in fruit bodies and mycelia,
      whereas carbohydrate contents were higher in the uninoculated and fermented
      wheat. Contents of total soluble sugars and polyols were 234.06, 111.70, 88.58,
      and 28.83 mg/g for fermented wheat, fruiting bodies, mycelia, and wheat,
      respectively. Contents of total free amino acids were in the descending order of
      mycelia > fermented wheat > fruiting bodies > wheat. Contents of total 5'
      nucleotides were in the descending order: fruiting bodies > mycelia > fermented
      wheat > wheat. Based on the results obtained, fruiting bodies and mycelia
      possessed highly intense umami taste. Overall, as a result of solid-state
      fermentation, fermented wheat contained more taste components and a higher
      equivalent umami concentration than wheat did.

PMID- 22135879
TI  - Isolation and in vitro cultivation of Auriculoscypha anacardiicola D.A. Reid et
      Manim., an insect-associated and potentially medicinal fungus from India.
AB  - Auriculoscypha anacardiicola, an obligate insect-associate and a potential
      medicinal fungus, is isolated and studied in vitro. Suitable methods for
      isolation and cultivation of the fungus have been developed. Incubating spore
      deposits made to fall from basidiomata on tap water agar seems to be the best
      method for developing cultures. Successful isolations were also accomplished from
      infected coccids. Cultures could not be developed from single basidiospores and
      from tissues of the basidiomata. Although production of ballistospores and
      blastospores as well as germ tube formation were observed at the time of
      germination of basidiospores, budding blastospores alone produced mycelial
      cultures. Observations such as the inability of single basidiospores to
      germinate, emergence of mycelium from a spore deposit, and the apparent
      conjugation of yeast cells indicate that dikaryotization resulting from fusion of
      compatible yeast cells is essential for development of mycelium in A.
      anacardiicola. The fungus grew well on all complex media tested. It seems that a
      purely synthetic medium devoid of any growth factors cannot support the growth
      ofA. anacardiicola and yeast extract seems to provide the required growth
      factors.

PMID- 22135880
TI  - Evaluation of Royal Sun Agaricus, Agaricus brasiliensis S. Wasser et al., aqueous
      extract in mice challenged with Salmonella enterica serovar Typhimurium.
AB  - This study investigated the effects of Agaricus brasiliensis S. Wasser et al.
      (=Agaricus blazei Murrill sensu Heinem.) aqueous extract on small intestinal sIgA
      levels, serum TNF-alpha, IFN-gamma and IL-10 levels, splenic index, bacterial
      translocation, and histology of small intestine, spleen, and liver from mice
      orally challenged with 10(6) CFU of Salmonella enterica serovar Typhimurium
      (SEST). Splenic index values as well as sIgA, TNF-alpha, IFN-gamma, and IL-10
      levels were not affected by either A. brasiliensis aqueous extract treatment or
      by pathogenic challenge. Typical colonies of SEST were recovered from liver,
      spleen, and mesenteric lymph nodes of challenged animals, but there was no
      significant difference in this translocation between groups treated or not with
      A. brasiliensis aqueous extract. Translocation was confirmed by histopathological
      analysis in mice challenged with SEST, which showed small and diffuse foci of
      mixed inflammatory infiltrate in hepatic parenchyma. In conclusion, A.
      brasiliensis aqueous extract as tested in the present study did not influence any
      of the variables selected to evaluate in vivo its immunomodulatory effect
      suggested in the literature.

PMID- 22135881
TI  - High genetic diversity in wild culinary-medicinal wood ear mushroom, Auricularia
      polytricha (Mont.) Sacc., in tropical China revealed by ISSR analysis.
AB  - The genetic diversity of 40 wild Auricularia polytricha strains within ten
      natural populations in tropical China and five cultivated strains were analyzed
      by using twelve inter-simple sequence repeat (ISSR) primers. At the species
      level, the percentage of polymorphic loci (P) = 99.8%, the effective number of
      alleles (Ne) = 1.3569, Nei's gene diversity (H) = 0.2398, Shannon information
      index (I) = 0.3896, and total genetic diversity (Ht)= 0.2346 indicate a high
      level of genetic diversity in wild A. polytricha. At the population level of the
      wild fungus, P = 43.51%, Ne = 1.2675, H = 0.1702, I = 0.2504. However, the
      genetic diversity of cultivated strains was the lowest of all populations (Ne =
      1.1584, H = 0.0940, I = 0.1440). A moderate degree of genetic differentiation
      (G(st) = 0.347) among the sampled wild populations was detected based on Nei's
      gene diversity analysis, suggesting that 65.3% of variation existed within this
      population. The high genetic variation level within wild populations may mostly
      result from a low level of gene flow (N = 0.9408) and random genetic drift.

PMID- 22135882
TI  - Ethnomycological studies of edible and medicinal mushrooms in the Mount Cameroon
      region (Cameroon, Africa).
AB  - Inhabitants of the Mount Cameroon region depend on the forest resources of the
      region for their livelihood, including the diverse use of macrofungi. With the
      increasing loss of forest due to exploitation and urbanization, they are liable
      to rapidly lose their indigenous knowledge of the forest resources, especially of
      mushrooms. An ethnomycological survey was conducted with the aim of documenting
      the indigenous knowledge of mushrooms as a prelude to conservation efforts. We
      also sought to assess the mycophilic and mycophobic tendencies of the
      inhabitants. It was revealed that traditionally, mushrooms were used as food,
      medicine, for mythological purposes, for aesthetics, and some poisonous species
      were also recorded. At least 15 different species were identified to be edible
      among the Bakweri people. Species used for ethnomedicine among the Bakweris
      belonged to several genera, including Termitomyces, Auricularia, Agaricus,
      Daldinia, Dictyophora, Pleurotus, Russula, Trametes, Chlorophyllum, and
      Ganoderma. Mushrooms were used as love charms, for dispelling evil spirits, and
      as part of cultural festivals.

PMID- 22135884
TI  - Professor Tetsuro Ikekawa on his 80th birthday.

PMID- 22135883
TI  - New dietary supplements from medicinal mushrooms: Dr Myko San--a registration
      report.
AB  - In December 2010 the Ministry of Health and Social Welfare of the Republic of
      Croatia registered tablet preparations AGARIKON. 1 and MYKOPROTECT. 1, developed
      by Dr Myko San-Health From Mushrooms Co., as dietary supplements. This may be the
      first time for a European manufacturer to successfully register its own medicinal
      mushroom products in a European country. As a product with a very broad spectrum
      of action, officially described as a preparation for immunity strengthening and
      general health improvement, AGARIKON.1 is a result of 20 years of research and
      practice, and is based on the formulation that has achieved the best tumor growth
      inhibition rates-above 90% on tumor cell lines of mouse squamous cell carcinoma
      and fibrosarcoma. Since the usage of massive dosages of proprietary blended
      liquid mushroom extracts in patients with breast, colorectal, lung, and other
      cancers significantly improved their survival rates, alleviated side effects of
      standard oncological therapies, improved their quality of life, and resulted in
      life prolongation-the very idea is that scientifically verified medicinal
      mushroom products can be used as powerful biological weapons to fight human
      malignancies. If progressive modem medicine were redefined in a more effective
      and humane way, cancer mycotherapy should be a part of a broad concept of
      biological prevention and therapy of cancer. Also, with a very broad spectrum of
      action, generally formulated as "to strengthen immunity," MYKOPROTECT. 1 is
      intended as an important element in the prevention and fighting of serious viral
      infections, whether they are caused by well-known viruses (hepatitis, HIV, etc.)
      or newly emerging ones.

PMID- 22135885
TI  - Characterization of blood beta-1,3-glucan and anti-beta-glucan antibody in
      hemodialysis patients using culinary-medicinal Royal Sun Agaricus, Agaricus
      brasiliensis S. Wasser et al. (Agaricomycetideae).
AB  - Beta-glucan is a major component of fungal cell walls and shows various
      immunopharmacological activities including antitumor activity. Previously, we
      detected anti-beta-glucan antibody in human sera. Anti-beta-glucan antibody
      participates in the immune response to fungal cell wall beta-glucan. Patients on
      dialysis are at high risk of infection including fungal infections. We examined
      the plasma beta-glucan level and the titer of anti-beta-glucan antibody in
      dialysis patients. We measured plasma beta-1,3-glucan concentrations with the
      limulus G test and anti-beta-glucan antibody titers by ELISA with Candida beta
      glucan-coated plates. We also examined the influence of the period of dialysis
      and the kind of dialysis membrane. The patients were positive for beta-1,3-glucan
      in their plasma. The anti-beta-glucan antibody titer was lower in the dialysis
      patients than in healthy volunteers. Long-term dialysis patients showed lower
      anti-beta-glucan antibody titers than short-term dialysis patients. No
      significant difference was found between the kinds of dialysis membrane. The
      titer of anti-beta-glucan antibody as recognition molecule of beta-glucan was low
      in dialysis patients compared with healthy volunteers. This is likely to be one
      factor explaining the sensitivity to infection of the dialysis patients. An
      appropriate application of culinary-medicinal mushroom such as Agaricus
      brasiliensis has potential for the prevention of fungal infection in dialysis
      patients.

PMID- 22135886
TI  - Effect of immunomodulating and antiviral agent of medicinal mushrooms (immune
      assist 24/7) on CD4+ T-lymphocyte counts of HIV-infected patients.
AB  - Immune enhancement through the use of natural products is a potentially valuable
      therapeutic modality in HIV-infected people, especially those who are not good
      candidates for aggressive ARV therapy. One such immune enhancement, a medicinal
      mushroom product from the United States, is Immune Assist 24/7. In this study the
      effect of Immune Assist 24/7, which is a naturally derived immune-modulating and
      antiviral agent, on CD4+ T-lymphocyte counts was evaluated in 8 HIV-infected
      patients at the Sunyani Regional Hospital (Ghana). The subjects were administered
      three tablets of 800 mg Immune Assist 24/7 once daily (2.4 g/day) and peripheral
      blood samples were drawn at baseline, day 30, and day 60, and the CD4+ count
      measured. The study revealed that Immune Assist 24/7, used as a sole therapeutic
      agent without additional ARV drugs, significantly increased CD4+ T-lymphocyte
      populations in all of the patients. In one patient, the CD4+ T-lymphocyte count
      went from 4 at the baseline, to 170 cells in 60 days, representing an increase of
      more than 4000%. In another patient, the CD4+ count went from 88 to 470 cells
      within the same period. Even in the patients with the highest CD4+ counts of
      around 800, there was a significant elevation in the CD4+ count noted. This study
      did not deal with the effect of Immune Assist 24/7 on other immune parameters
      such as CD3+ T-lymphocyte count, natural killer cells count, or viral load among
      HIV-infected patients. These initial results are promising, and indicate the
      potential value of further evaluating the effects of Immune Assist 24/7 on other
      immune parameters and viral load among HIV patients, administered either as a
      sole therapeutic agent, as an adjuvant with standard ARV therapy, or in
      comparison with standard ARV therapy alone.

PMID- 22135887
TI  - Preparation of Black Hoof medicinal mushroom Phellinus linteus (Berk. et M.A.
      Curt.) Teng (Aphyllophoromycetideae) beta-glucan sulfate and in vitro tumor cell
      growth inhibitory activity.
AB  - Polysaccharide beta-glucans were extracted from the medicinal mushroom Phellinus
      linteus (Hymenochaetaceae, Aphyllophoromycetideae) and subjected to sulfation.
      Chemical modification of the beta-glucan was confirmed by structural analysis,
      and its biological properties were compared with those of native beta-glucan. The
      results of Fourier transform infrared spectroscopy and elemental analysis
      indicated that successive preparation of the sulfated derivative yielded a degree
      of substitution of 0.47. Nitric oxide production measured by the bronchoalveolar
      lavage (BAL) experiments increased 1.5-fold after sulfation. In addition, the
      introduction of sulfate groups into the beta-glucan chains improved in vitro
      growth inhibitory activity against SNU-C2A cells. Therefore, sulfated beta-glucan
      extracted from Ph. linteus may be beneficial for immune support due to its
      incorporation of functional groups into its polymer structure.

PMID- 22135888
TI  - In vitro antitumor activity and structure characterization of ethanol extracts
      from wild and cultivated Chaga medicinal mushroom, Inonotus obliquus (Pers.:Fr.)
      Pilat (Aphyllophoromycetideae).
AB  - Inonotus obliquus (Pers.:Fr.) Pilat has been traditionally used as a folk remedy
      for treatment of cancers, cardiovascular disease and diabetes in Russia, Poland,
      and most of the Baltic countries, but natural reserves of this fungus have nearly
      been exhausted. This study was designed to investigate the artificial cultivation
      of I. obliquus and the antitumor activity of its tissues. The ethanol extract of
      cultivated sclerotium had the highest cell growth inhibitory rate (74.6%) as
      determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay. 78% of the bags produced sclerotia and only 6.17 g/bag of sclerotium
      was obtained. Extracts of the cultivated fruiting body showed 44.2% inhibitory
      activity against tumor cells. However, the yield was as high as 18.24 g/bag, and
      98% of the bags produced fruiting body. The results of gas chromatography-mass
      spectroscopy (GC-MS) showed that similar compounds were extracted from the wild
      and cultivated samples. The principal compounds observed were lanosterol,
      inotodiol, and ergosterol. Their percentages of the mass fraction were 86.1,
      59.9, and 71.8% of the total, for the wild sclerotium, cultivated sclerotium, and
      cultivated fruiting body, respectively. Ergosterol was found to be much higher
      (27.32%) in cultivated fruiting body. We conclude that cultivated fruiting body
      of I. obliquus obtained by inoculation of the substrate with spawn mycelium of
      the fifth generation could serve as an ideal substitute for the wild I. obliquus.

PMID- 22135889
TI  - Anticancer effects of fraction isolated from fruiting bodies of Chaga medicinal
      mushroom, Inonotus obliquus (Pers.:Fr.) Pilat (Aphyllophoromycetideae): in vitro
      studies.
AB  - The medicinal mushroom Chaga, Inonotus obliquus (Pers.:Fr.) Pilat
      (Hymenochaetaceae), has been used in folk medicine in Russia, Poland, and most of
      the Baltic countries, as a cleansing and disinfecting measure, and as decoctions
      for stomach diseases, intestinal worms, liver and heart ailments, and cancer
      treatment. Many reports have been published concerning the health promoting
      functions of this mushroom, including antibacterial, hepatoprotective, anti
      inflammatory, antitumor, and antioxidant activities. The purpose of the present
      study was evaluation of in vitro anticancer activity of fraction IO4 isolated
      from I. obliquus. The effect on cell proliferation, motility and viability was
      assessed in a range of cancer and normal cells. Chaga fraction prepared from
      dried fruiting bodies was subjected to anticancer evaluation in human lung
      carcinoma (A549), colon adenocarcinoma (HT-29), and rat glioma (C6) cell
      cultures. Human skin fibroblasts (HSF), bovine aorta endothelial cells (BAEC),
      models of rat oligodendrocytes (OLN-93), hepatocytes (Fao), rat astroglia, and
      mouse neurons (P19) were applied to test toxicity in normal cells. The following
      methods were applied: tumor cell proliferation (MTT assay and BrdU assay),
      cytotoxicity (LDH assay), tumor cell motility (wound assay), tumor cell
      morphology (May-Grunwald-Giemsa staining), and death detection (ELISA). Chaga
      fraction elicited anticancer effects which were attributed to decreased tumor
      cell proliferation, motility and morphological changes induction. Of note is the
      fact that it produced no or low toxicity in tested normal cells. The data
      presented could open interesting paths for further investigations of fraction IO4
      as a potential anticancer agent.

PMID- 22135890
TI  - Antioxidant and cytotoxic activities of ethanolic extracts and isolated fractions
      of species of the genus Phellinus Quel. (Aphyllophoromycetideae).
AB  - Ethanolic extracts of fruit bodies of 5 species (8 strains) of the genus
      Phellinus, and isolated fractions derived from 1 of these extracts (Ph. baumii PB
      10), were evaluated for antioxidant activity, inhibitory effects on the growth of
      human tumor cells, and the capacity to protect PC12 cells against H2O2-induced
      oxidative damage. Extracts of all 8 strains of Phellinus spp. exhibited
      antioxidant activity and protected PC12 cells against oxidative damage at
      different magnitudes of potency. The strongest antioxidant activity was exhibited
      by extracts of Ph. baumii PB-10, with recorded IC50 values for superoxide radical
      and hydrogen peroxide scavenging activity of 3.76 microg/mL and 4.24 microg/mL,
      respectively. Radical-scavenging activity and protection levels against H2O2
      induced damage to PC12 cells were highly correlated with the flavonoid content of
      the extracts and isolated fractions. All the extracts inhibited L1210, SW620, and
      MCF-7 tumor cell proliferation at 200 microg/mL concentrations, but inhibition
      was not correlated with the flavone content of the test samples and was clearly
      dependent upon the presence of other, as yet, unidentified components. Our data
      indicate that fruit bodies of species of the genus Phellinus represent a
      potentially valuable source of natural antioxidants of relevance to both the
      health and food industries.

PMID- 22135891
TI  - A comparative assessment of the potential of polysaccharide production and
      intracellular sugar composition within Lingzhi or Reishi medicinal mushroom,
      Ganoderma lucidum (W.Curt.:Fr.)P. Karst. (Aphyllophoromycetideae).
AB  - Ganoderma lucidum is a well-known medicinal mushroom species in which
      polysaccharides are one of the major sources of biological activity. The species
      was considered as a species-complex due to significant variations in
      morphological, biochemical, and genetic features among populations with a
      worldwide distribution. This fact was the basis for setting the aim of this
      research: to study intraspecific diversity in polysaccharide production and
      intracellular sugar composition among selected G. lucidum strains. The presence
      ofintraspecific diversity among 10 G. lucidum strains, from different areas
      worldwide, was noted. Values of produced mycelia biomass and intracellular
      polysaccharides were found in wide ranges (3.1 - 28.2 g L(-1) and 20.0 - 53.3 mg
      g(-1), respectively), while differences in extracellular polysaccharide amounts
      were minor (0.2 - 1.5 mg mL(-1)). The significant quantitative and qualitative
      differences in intracellular sugar composition were noted. Glucose was the
      predominant sugar in almost all strains except one (HAI 447), where sucrose was
      dominant. The potential of polysaccharide production and intracellular sugar
      composition could be one more taxonomic criterion for strain characterization
      within G. lucidum. The differences in intracellular sugar composition and
      proportions could be reflected in features of produced polysaccharides and also
      in their biological activities.

PMID- 22135892
TI  - Lectin activity of species of genus Cerrena S.F. Gray (Aphyllophoromycetideae) in
      submerged fermentation of lignocellulosic materials.
AB  - The capability of 5 strains of 2 species of genus Cerrena
      (Aphyllophoromycetideae) to express hemagglutinating activity (HA) was evaluated
      in submerged fermentation of 7 lignocellulosic materials of different chemical
      compositions. Among the lignocellulosic substrates tested, walnut pericarp,
      followed by mandarin and kiwi peels provided the highest specific HA of C.
      unicolor IBB 300; walnut leaves and pericarp appeared to be the best substrates
      for the accumulation of lectin by C. unicolor IBB 301, whereas the fermentation
      of kiwi peels ensured the highest HA of C. unicolor IBB 302. The highest HA was
      detected in C. maxima IBB 402 cultivation in submerged fermentation of walnut
      leaves (64103 U/mg), mandarin (33333 U/mg) and kiwi peels (28571 U/mg). Moreover,
      the fermentation of walnut pericarp and leaves provided the secretion of high
      lectin levels in culture liquid (9143 U/mg). The carbohydrate specificity of
      tested preparations significantly depended on both fungus strain and
      lignocellulosic growth substrate. By substitution of lignocellulosic material, it
      is possible to regulate lectin production and to obtain a preparation with
      different specificity toward carbohydrates.

PMID- 22135893
TI  - Chemical, pharmacological, and biological characterization of the culinary
      medicinal honey mushroom, Armillaria mellea (Vahl) P. Kumm. (Agaricomycetideae):
      a review.
AB  - Recently, studies have been conducted on the chemical composition of fruiting
      bodies of the culinary-medicinal Honey mushroom, Armillaria mellea (Vahl.) P.
      Kumm. (higher Basidiomycetes). It is considered in Europe and Asia as edible and
      medicinal, when appropriately prepared, and has demonstrated the presence of
      different groups of organic compounds, including carbohydrates, sterols,
      sphingolipids, fatty acids, sesquiterpenes, non-hallucinogenic indole compounds,
      peptides, enzymes, adenosine derivatives, and many other components. Most of
      these metabolite groups possess potential therapeutic and dietary values. The
      results of quantitative analyses of indole compounds and heavy metals signal
      potential health hazards for humans. Some of the studies reviewed herein describe
      in detail the mechanism of symbiosis between A. mellea and the orchid species
      Gastrodia elata. This orchid is native to Asia, Australia, and New Zealand, and
      is used in therapeutics in official Chinese medicine.

PMID- 22135894
TI  - Properties and potential applications of the culinary-medicinal cauliflower
      mushroom, Sparassis crispa Wulf.:Fr. (Aphyllophoromycetideae): a review.
AB  - Sparassis crispa is a culinary-medicinal mushroom that has recently become
      popular in Korea, China, Japan, Germany, and the USA. S. crispa is a good source
      of food and nutraceuticals, or dietary supplements, due to its rich flavor
      compounds and beta-glucan content. This review is a comprehensive summary of its
      distribution, growth, management, general constituents, functional ingredients,
      as well as its current and potential medicinal and other applications.

PMID- 22135895
TI  - The influence of different submerged cultivation conditions on mycelial biomass
      and protease production by Lentinus citrinus Walleyn et Rammeloo DPUA 1535
      (Agaricomycetideae).
AB  - The influence of different carbon and nitrogen sources, pH of the culture medium,
      and temperature and period of cultivation on mycelial biomass production and
      protease activity by Lentinus citrinus DPUA 1535 were investigated in submerged
      culture. A 2(5) full factorial design with three central points was employed, and
      the results showed that at a significance level of 95% only nitrogen source and
      temperature were statistically significant for mycelial biomass production. On
      the other hand, for protease activity all factors and some interactions were
      significant, and the temperature and nitrogen source had the most significant
      effect. The best condition for mycelial biomass production (5.76 mg mL(-1)) and
      protease activity (32.3 U mL(-1)) was obtained in medium formulated with 0.5%
      soluble starch, 0.2% gelatin, pH 7.0, 25 degrees C, in 5 days.

PMID- 22135896
TI  - Cultivation of the culinary-medicinal Lung Oyster mushroom, Pleurotus pulmonarius
      (Fr.) Quel. (Agaricomycetideae) on grass plants in Taiwan.
AB  - Cultivation of the culinary-medicinal Lung Oyster mushroom, Pleurotus
      pulmonarius, on the stalks of three grass plants, i.e., Panicum repens,
      Pennisetum purpureum, and Zea mays were investigated. The effects of various
      combinatorial substrates on mushroom mycelial growth and yield calculated as
      biological efficiency (BE) were determined. Among 9 experimental substrates, the
      most suitable substrate for mycelial growth was 45ZMS:45S, followed by 45PRS:45S;
      their mycelial growth rates were obviously quicker than that of the control
      substrate. The BEs of all the experimental substrates respectively containing P.
      repens stalk, P. purpureum stalk and Z. mays stalk were higher than that of the
      control (39.55%) during the 2.5 months of cultivation period. The best substrate
      in terms of BE was 60ZMS:30S (58.33%), followed by 45PRS:45S (57.16%), 45ZMS:45S
      (49.86%), and 30ZMS:60S (47.20%). Based on the BE of the tested substrates, Z
      mays stalk appeared to be the best alternative material for the production of P.
      pulmonarius.

PMID- 22135897
TI  - Professor Shu-Ting Chang on his 80th birthday.

PMID- 22135898
TI  - Mechanism of nitric oxide production in macrophages treated with medicinal
      mushroom extracts (review).
AB  - Nitric oxide (NO) is a gas with highly reactive radicals and is an important
      signal molecule in living organisms with diverse pathophysiological functions.
      Inducible NO synthase (iNOS) can be expressed in macrophages and is able to
      induce NO production. Studies have proposed that mushroom extracts can promote or
      inhibit NO production in macrophages through acting on iNOS, nuclear factor kappa
      B, and other signaling pathways. This article is dedicated to the mechanism of
      mushroom extracts affecting NO secretion in macrophages.

PMID- 22135899
TI  - Anti-infective properties of the melanin-glucan complex obtained from medicinal
      tinder bracket mushroom, Fomes fomentarius (L.: Fr.) Fr.
      (Aphyllophoromycetideae).
AB  - The goal of this investigation was to comparatively study the efficiency of
      traditionally used anti-infective drugs and biopolymer complexes originated from
      the medicinal mushroom Fomes fomentarius (L.:Fr.) Fr.: 1) water-soluble melanin
      glucan complex (MGC; -80% melanins and -20% beta-glucans) and 2) insoluble chitin
      glucan-melanin complex (ChGMC; -70% chitin, -20% beta-glucans, and -10%
      melanins). Infectious materials (Helicobacter pylori, Candida albicans, and
      Herpes vulgaris I and HIV-1(zmb) were used in pure cultures of in vitro and in
      vivo models on experimental animals. Comparison studies of fungal biopolymers and
      effective modern antifungal, antibacterial, and antiviral drugs were used in in
      vitro models. The comparative clinical efficiency of ChGMC and of etiotropic
      pharmaceuticals in models of H. pylori, C. albicans, and H. vulgaris I infection
      contamination were studied. Using in vitro models, it was established that MGC
      completely depresses growth of C. albicans. MGC had an antimicrobial effect on H.
      pylori identical to erythromycin in all concentrations, and had a stronger action
      on this bacterium than other tested antibiotics. Tested MGC possesses
      simultaneously weak toxicity and high anti-HIV-1 activity in comparison with
      zidovudine (Retrovir). The obtained results show that CLUDDT therapy in Wistar
      rats with the application of ChGMC is, on average, 1.35-1.43 times as effective
      as a traditional one. Considering the absence of MGC and ChGMC toxic properties
      on blood cells even in very high concentrations, these complexes may be used as a
      source of biopolymers for the creation of essentially new agents for wide
      application in infectious pathology.

PMID- 22135900
TI  - The Shaggy Inc Cap medicinal mushroom, Coprinus comatus (O.F.Mull.: Fr.) Pers.
      (Agaricomycetideae) substances interfere with H2O2 induction of the NF-kappaB
      pathway through inhibition of Ikappaalpha phosphorylation in MCF7 breast cancer
      cells.
AB  - Breast cancer is the most commonly diagnosed cancer among women. Currently, there
      is no effective therapy for malignant estrogen-independent breast cancer. In our
      study, we used hydrogen peroxide, a well-known strong oxidative reagent capable
      of activating the nuclear factor kappa B (NF-kappaB) transcription factor. The
      IC50 value of the culinary-medicinal Shaggy Inc Cap mushroom Coprinus comatus
      culture liquid crude extract on MCF7 cell viability was found to be as low as 76
      microg/mL, and the IC50 value of C. comatus ethyl acetate extract was only 32
      microg/ mL. Our results also showed that both extracts significantly affected
      IkappaBalpha phosphorylation in a dose-dependent manner. The effect of ethyl
      acetate extract was comparable to the effect of curcumin, a known NF-kappaB
      pathway inhibitor, and seemed to be the most active inhibitor of H2O2-dependent
      IkappaBalpha phosphorylation. In addition, the data obtained showed that only
      ethyl acetate extract inhibited the activity of IKK complex, at close to 90% as
      compared to the control of the untreated sample. These results suggest that C.
      comatus contains potent compounds capable of inhibiting NF-kappaB function and
      also possibly acts as an antitumor agent.

PMID- 22135901
TI  - An antifungal protein from the culinary-medicinal beech mushroom, Hypsizygus
      marmoreus (Peck) Bigel. (Agaricomycetideae).
AB  - An antifungal protein (HM-af) was purified from the culinary-medicinal mushroom
      Hypsizygus marmoreus. The results of sodium dodecyl sulfate polyacrylamide gel
      electrophoresis and matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry of HM-af indicated that its molecular mass was 9.5 kDa. The N
      terminal amino acid sequence of HM-af showed homology to ribonuclease H from
      Clostridium thermocellum. HM-af showed the antifungal activity against Flammulina
      velutipes.

PMID- 22135902
TI  - Potential activity of aqueous extract of culinary-medicinal Lion's Mane mushroom,
      Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) in accelerating
      wound healing in rats.
AB  - This study was conducted to evaluate the effects of topical application of
      aqueous extract of Hericium erinaceus fruiting bodies (HEFB) on the rate of wound
      healing enclosure and histology of the healed wound. Five groups of male Sprague
      Dawley rats were experimentally wounded in the posterior neck area. A uniform
      wound area of 2.00 cm in diameter, using a circular stamp, was excised from the
      nape of the dorsal neck of all rats with the aid of a round seal. The animal
      groups were topically treated, respectively, with 0.2 mL each of sterilized
      distilled water (sdH2O); Intrasite gel; and 20, 30, and 40 mg/mL HEFB.
      Macroscopically, those rats whose wounds were dressed with HEFB and those in the
      Intrasite gel-treated group healed earlier than those treated with sdH2O.
      Histological analysis of healed wounds dressed with HEFB showed less scar width
      at wound enclosure and the healed wound contained fewer macrophages and more
      collagen with angiogenesis, compared to wounds dressed with sdH2O. In conclusion,
      wounds dressed with HEFB significantly enhanced the acceleration of wound healing
      enclosure in rats.

PMID- 22135903
TI  - Statistical optimization of polysaccharide production by submerged cultivation of
      Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.: Fr.) P. Karst.
      MTCC 1039 (Aphyllophoromycetideae).
AB  - Response surface methodology was employed to optimize the concentration of four
      important cultivation media components such as cottonseed oil cake, glucose,
      NH4Cl, and MgSO4 for maximum medicinal polysaccharide yield by Lingzhi or Reishi
      medicinal mushroom, Ganoderma lucidum MTCC 1039 in submerged culture. The second
      order polynomial model describing the relationship between media components and
      polysaccharide yield was fitted in coded units of the variables. The higher value
      of the coefficient of determination (R2 = 0.953) justified an excellent
      correlation between media components and polysaccharide yield, and the model
      fitted well with high statistical reliability and significance. The predicted
      optimum concentration of the media components was 3.0% cottonseed oil cake, 3.0%
      glucose, 0.15% NH4Cl, and 0.045% MgSO4, with the maximum predicted polysaccharide
      yield of 819.76 mg/L. The experimental polysaccharide yield at the predicted
      optimum media components was 854.29 mg/L, which was 4.22% higher than the
      predicted yield.

PMID- 22135904
TI  - Production of bioactive exopolysaccharides from bitter medicinal mushroom,
      Antrodia camphorata (M. Zang et C.H. Su) Sh.H. Wu et al. (Aphyllophoromycetideae)
      in submerged cultivation.
AB  - This study examines the effects of various fructose concentrations in media on
      the production and quality of bioactive exopolysaccharides (EPS) from Bitter
      medicinal mushroom, Antrodia camphorata in submerged cultures. The fructose in
      media of submerged cultures of A. camphorata significantly affected the
      production, average molecular weight (Mn), and antioxidant activity of
      exopolysaccharides. The specific growth rate decreased monotonically from 0.33 to
      0.25 1/day as the fructose concentration increased from 10 to 60 g/L; however,
      maximum production and productivity for EPS increased from 75.23 to 164.87 mg/L
      and 6.27 to 9.70 mg/L/day, respectively. In addition, the fed-batch culture used
      in this study significantly improved the production of EPS (2.43-fold
      enhancement, from 75.23 to 182.99 mg/L), number average molecular weights of EPS
      (1.47-fold enhancement, from 5.44 x 10, to 7.98 x 10(5) Da),
      protein/exopolysaccharide ratios (1.63-fold enhancement, from 16% to 26%), and
      antioxidant activity of EPS (1.32-fold enhancement, from 60% to 79%), as compared
      with corresponding properties of batch fermentation at 10 g/L fructose in an air
      lift bioreactor. The antioxidant activity of EPS was highly correlated with
      number average molecular weights (R2 = 0.90) and protein/exopolysaccharide ratios
      (R2 = 0.96). The positive results of this research have successfully verified the
      promotion efficiency on the production and quality of EPS from the medicinal
      mushroom A. camphorata.

PMID- 22135905
TI  - Preparation of culinary-medicinal maitake mushroom, Grifola frondosa (Dicks.:
      Fr.) S.F. Gray (Aphyllophoromycetideae)-fermented wheat and its antioxidant
      properties.
AB  - The optimization of solid-state fermentation conditions for mycelial growth in
      wheat by culinary-medicinal maitake mushroom, Grifola frondosa (Dicks.: Fr.) S.F.
      Gray was studied. The results from the center of the design analysis showed that
      the recommended optimal conditions for carbon, nitrogen sources, and temperature
      were 19 mg lactose/g, 2.0 mg malt extract/g, and 30 degrees C, respectively.
      Under these conditions, the mycelial biomass of 533.1 mg/g was obtained in
      fermented wheat, comparable to that (545.7 mg/g) obtained using the one-factor-at
      a-time method. Based on the results obtained, EC50 values of ethanolic and hot
      water extracts from fermented wheat were 1.13-15.27 mg/mL, indicating that
      fermented wheat was effective in antioxidant activity, reducing power, scavenging
      ability on 1,1-diphenyl-2-picrylhydrazyl radicals, and chelating ability on
      ferrous ions. Total phenol contents of both extracts were 13.35 and 23.01 mg/g,
      respectively. Accordingly, the information obtained would be applicable for the
      cultivation and consumption of G. frondosa-fermented wheat to provide its
      beneficial health effects.

PMID- 22135907
TI  - Long-term preservation, regeneration, and cultivation of Paecilomyces tenuipes
      (Peck) Samson (Ascomycetes), an entomopathogenic fungus inoculated into the
      silkworm larva of Bombyx mori.
AB  - Paecilomyces tenuipes reportedly have anticancer and immune activities, along
      with various other medicinal uses. Cultured products with P. tenuipes are
      certified for use in food in South Korea, and processed goods containing this
      fungus have been developed in many countries, particularly South Korea, Japan,
      and China. Research on mass production technology-procured raw materials for the
      manufacture of P. tenuipes is very important; however, cultures of the fungus
      have been unstable. This study identified stable cultivation conditions, focusing
      on growth inhibition and revitalization. Moisture regulation and preservation of
      pupae inoculated with P. tenuipes were used to control growth inhibition and
      revitalization. When inoculated silkworm pupae were dehydrated to 4% moisture and
      preserved freeze-dried or at -70 degrees C, -20 degrees C, or 4 degrees C, the
      mycelia in their bodies were able to survive for 14 d. Inoculated silkworm pupae
      were rehydrated for 3 h and the mycelia within their bodies were recovered at
      94.3-96.3%. Silkworm pupae at 4% moisture were able to survive for 135 d at
      temperatures < 4 degrees C and for 1 y after freeze-drying. Optimal conditions
      for synnemata induction were 25 degrees C and 100-300 1x.

PMID- 22135906
TI  - Partial purification and characterization of polyphenoloxidase from culinary
      medicinal Royal Sun mushroom (the Himematsutake), Agaricus brasiliensis S. Wasser
      et al. (Agaricomycetideae).
AB  - The Royal Sun mushroom, the Himematsutake culinary-medicinal mushroom, Agaricus
      brasiliensis has several polyphenoloxidase activities in a broad sense. Here we
      report the partial purification of tyrosinase-type polyphenoloxidase (PPO). PPO
      is purified from A. brasiliensis without browning using a two-phase partitioning
      with Triton X-114 and ammonium sulfate fractionation. Partially denaturing SDS
      PAGE (sodium dodecyl sulfate-polyacrylamide electrophoresis) staining with L-3,4
      dihydroxyphenylalanine was performed and the indicated molecular sizes were
      approximately 70 kDa and 45 kDa. The purified enzyme is in its latent state and
      can be activated maximally in the presence of 1.6 mM sodium dodecyl sulfate
      (SDS). This enzyme catalyzes two distinct reactions, monophenolase and
      diphenolase activity, and the monophenolase activity showed a lag time typical of
      polyphenoloxidase. The K(m) value for 4-tert-butylcatechol was quite similar in
      the presence and absence of SDS, but the apparent V(max) value was increased 2.0
      fold by SDS. Mimosine was a typical competitive inhibitor with K(i) values of
      138.2 microM and 281.0 microM n the presence and absence of SDS, respectively.

PMID- 22135908
TI  - Blockade of mGluR5 reverses abnormal firing of subthalamic nucleus neurons in 6
      hydroxydopamine partially lesioned rats.
AB  - Activation of metabotropic glutamate receptor 5 (mGluRs) in the subthalamic
      nucleus (STN) results in burst-firing activity of STN neurons, which is similar
      to that observed in Parkinson's disease (PD). We examined the effects of chronic
      and systemic treatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a
      selective mGluR5 antagonist, in firing activity of STN neurons in partially
      lesioned rats by 6-hydroxydopamine (6-OHDA). In 6-OHDA-lesioned rats treated with
      vehicle, injection of 6-OHDA (4 microg) into the medial forebrain bundle produced
      a partial lesion causing 36% loss of tyrosine hydroxylase-immunoreactive (TH-ir)
      neurons in the substantia nigra pars compacta (SNpc). The 6-OHDA lesion in
      vehicle-treated rats showed an increasing firing rate and a more irregular firing
      pattern of STN neurons. Whereas chronic, systemic treatment of MPEP (3 mg/kg/day,
      14 days) produced neuroprotecive effects on the TH-ir neurons and normalized the
      hyperactive firing activity of STN neurons in 6-OHDA partially lesioned rats.
      These data demonstrate that partial lesion of the nigrostriatal pathway increases
      firing activity of STN neurons in the rat, and chronic, systemic MPEP treatment
      has the neuroprotective effect and reverses the abnormal firing activity of STN
      neurons, suggesting that MPEP has an important implication for the treatment of
      PD.

PMID- 22135910
TI  - Effect of interleukin-6 (IL-6) on the vascular smooth muscle contraction in
      abdominal aorta of rats with streptozotocin-induced diabetes.
AB  - Patients with type 1 diabetes are at a risk of hypertension. However, the
      mechanisms behind the findings are not completely known. The aim of the present
      study was to investigate involvement of interleukin-6 (IL-6) on the contraction
      of abdominal aorta in rats with type 1 diabetes. IL-6 levels in the plasma of
      rats with streptozotocin (STZ)-induced diabetes were determined by ELISA. The
      abdominal aorta was dissected free of fat and connective tissues and then cut
      into spiral rings. The endothelium-denuded strip was vertically suspended in
      tissue chambers containing 5 ml Krebs solution at 37 degrees C and bubbled
      continuously with 95% O2-5% CO2. The effects of phenylephrine (Phe) on the
      contractile responses of abdominal aorta were recorded. The effects of IL-6 and
      anti-rat IL-6 antibody on the Phe-induced response were also examined. Plasma
      levels of IL-6 increased time-dependently in rats with STZ-induced diabetes. Phe
      caused concentration-dependent contraction in aortic rings. Phe-induced
      contractions were higher in vascular strips of STZ-induced diabetic rats than
      that of control rats. Pretreatment of vascular strips with IL-6 for 1 h did not
      cause contraction but enhanced the contraction in response to Phe. Treatment of
      the vascular strips with an anti-IL-6 antibody for 1 h decreased the Phe-induced
      contractions. These results suggest that IL-6 causes vascular smooth muscle
      contraction in abdominal aorta of rats with type 1 diabetes.

PMID- 22135909
TI  - Paroxetine-induced Ca2+ movement and death in OC2 human oral cancer cells.
AB  - The effect of the antidepressant paroxetine on cytosolic free Ca2+ concentrations
      ([Ca2+]i) in OC2 human oral cancer cells is unclear. This study explored whether
      paroxetine changed basal [Ca2+]i levels in suspended OC2 cells by using fura-2 as
      a Ca2+-sensitive fluorescent dye. Paroxetine at concentrations between 100-1,000
      microM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was
      reduced by 50% by removing extracellular Ca2+. Paroxetine-induced Ca2+ influx was
      inhibited by the store-operated Ca2+ channel blockers nifedipine, econazole and
      SK&F96365, and protein kinase C modulators. In Ca2+-free medium, pretreatment
      with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished
      paroxetine-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did
      not alter paroxetine-induced [Ca2+]i rise. Paroxetine at 10-50 microM induced
      cell death in a concentration-dependent manner. The death was not reversed when
      cytosolic Ca2+ was chelated with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid. Propidium iodide staining suggests that apoptosis plays a role
      in the death. Collectively, in OC2 cells, paroxetine induced [Ca2+]i rise by
      causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum
      and Ca2+ influx via store-operated Ca2+ channels in a manner regulated by protein
      kinase C and phospholipase A2. Paroxetine (up to 50 microM) induced cell death in
      a Ca2+-independent manner.

PMID- 22135911
TI  - A radioimmunoassay for rat ghrelin: evaluation of method and effects of
      nonylphenol on ghrelin secretion in force-fed young rats.
AB  - Antiserum YJC 13-31 against the rat ghrelin conjugated to bovine serum albumin
      (BSA) was produced in the rabbit and a double antibody radioimmunoassay (RIA) for
      ghrelin has been developed. Characterization results of this antiserum revealed
      no cross-reaction with human growth hormone and somatostatin. Weak cross
      reactions with insulin (0.1%), rat growth hormone (0.1%) and glucagon (0.3%) were
      observed, which scarcely interfered the assay system. The sensitivity of this RIA
      was 5 pg per assay tube. With the rat serum samples, the within-assay precision
      was 7.1% and the between-assay precision was 12.3%. The RIA was also available to
      detect the ghrelin in rat tissue extracts with good parallelism to the rat
      ghrelin standard. In application, the serum ghrelin and corticosterone levels in
      weaned rats were measured by RIA. Gavage of saline was sufficient to raise serum
      ghrelin from 2.6 +/- 0.18 to 6.7 +/- 0.7 ng/ml (P < 0.01). Gavage with
      nonylphenol (NP) suppressed the elevation of serum ghrelin levels in a dose
      dependent manner. Besides, gavages of saline elevated the serum levels of
      corticosterone from 108.8 +/- 13.5 to 188.7 +/- 23.5 ng/ml (P < 0.01) but the
      elevation effects of corticosterone from gavages were overcome by NP in the low
      dose of 50 mg/kg. It can be speculated that ingestion of NP is harmful to young
      animals during growth and environmental adaptation.

PMID- 22135912
TI  - Clinicopathological significance of CEACAM1 gene expression in breast cancer.
AB  - Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell
      adhesion molecule expressed in a variety of cell types. The role of CEACAM1 in
      breast cancer development and progression is largely unknown. Immunohistochemical
      analysis was used to examine CEACAM1 expression in breast cancer with long-term
      follow-up. CEACAM1 expression level in primary breast cancer was low or
      undetectable. In 65% of the cases, CEACAM1 expression within tumor tissue was
      lower than that in adjacent tissues. In 20% of the cases, CEACAM1 was negative.
      In 28.3% of cases, equivalent CEACAM1 expression level was detected in tumor and
      adjacent tissues. The expression level of CEACAM1 in tumor tissue was negatively
      correlated with patient mortality, while positively correlated with the
      expression level of ER+/PR+. CEACAM1 expression was not related with patients'
      age, pathological classification, lymphatic involvement and the size of tumor.
      The down-regulation of CEACAM1 was correlated with negative ER-/PR- and might be
      attributed to the malignant process of breast cancer. The prognosis of the
      patients with low CEACAM1 expression and high tumor pathological grade were
      poorer than those patients with high expression and low pathological grade, P <
      0.05. Clinically, it is possible to predict the prognosis among the patients of
      breast cancer by measuring CEACAM1 gene expression in the tumor tissues.

PMID- 22135913
TI  - Physiological demands of cyclists during an ultra-endurance relay race: a field
      study report.
AB  - This study was to describe and compare the physiological demands of ultra
      endurance cyclists during a 24 h cycling relay race. Eleven male athletes (means
      +/- SD: 34.8 +/- 5.6 years; 71.6 +/- 4.9 kg; 174.6 +/- 7.3 cm; BMI 23.5 +/- 0.5
      kg/m2; VO2 max: 66.0 +/- 6.4 ml/kg/min) participated in the study; eight in teams
      with a format of four riders (4C) and three in teams with six riders (6C). To
      investigate exercise intensity, heart rate (HR) was recorded while cycling using
      portable telemetric monitors. Three different exercise intensities were defined
      according to the reference HR values obtained during a pre race laboratory
      incremental VO2 max test: Zone I (< anaerobic threshold [AT]), Zone II (between
      AT and the respiratory compensation point [RCP]), Zone III (> RCP). Total volume
      and intensity were integrated as a single variable (training impulse: TRIMP). The
      score for TRIMP in each zone was computed by multiplying the accumulated duration
      in this zone by a multiplier for this particular zone of exercise intensity. The
      average intensity did not differ between cyclists in 4C (means +/- SD; 4C: 87 +/-
      3 HRmax) and 6C (87 +/- 1% of HRmax), despite the higher volume performed by 4C
      (means +/- SD; 4C: 361 +/- 65; 6C: 242 +/- 25 per min; P = 0.012). These
      differences in total exercise volume significantly affected the values TRIMP
      accumulated (means +/- SD; 4C: 801 +/- 98, confidence interval [CI] 95%: 719 -
      884; 6C: 513 +/- 25, CI 95%: 451 - 575; P = 0.012). The ultra-endurance threshold
      of 4C and 6C athletes lies at about 87% of HRmax for both. Although the intensity
      profile was similar, the TRIMP values differed significantly as a consequence of
      the higher volume performed by the 4C cyclists.

PMID- 22135914
TI  - A biological validation procedure for the measurements of fecal outputs and fecal
      cortisol metabolites in male Syrian hamsters.
AB  - Monitoring fecal outputs and fecal cortisol metabolites (FCM), a noninvasive
      technique, has been used to investigate physiological responses to stress and
      relationships between hormones and behavior in an increasing number of species.
      The aim of this study was to investigate whether measurements of fecal outputs
      and FCM can be used as indexes to repeatedly and precisely monitor stress levels
      in male Syrian hamsters using a social defeat as a biological validation method.
      The feces voided by each animal were collected every 3 h for at least 1 day
      before and after experiencing a single fighting interaction, and the extracted
      FCM during the pre- and post-fight phases was quantified by enzyme immunoassays.
      During the pre-fight baseline phase, both the number of fecal pellets and the FCM
      levels fluctuated throughout the whole day. Although the number of fecal pellets
      did not differ between the dark and light cycles, the levels of FCM were
      significantly higher during the dark cycle than during the light cycle. During
      the post-fight phase, the experience of fighting did not result in a significant
      difference in the number of fecal pellets per hour between the winner and loser
      groups, but did considerably increase the total amount of fecal outputs in both
      groups. The level of FCM was significantly higher in the loser group than in the
      winner group during the 1st and 7th 3-h collection periods after the fight, which
      indicated that the experience of defect affected the behavioral and physiological
      responses of the losers. Our findings suggest that measurement of FCM is
      sensitive enough to distinguish the stress levels between winners and losers
      after experiencing a fight. The measurements of fecal outputs and FCM levels
      provide new opportunities to longitudinally and frequently monitor behavioral and
      hormonal responses to stress in hamsters and other small laboratory animals.

PMID- 22135915
TI  - Alterations of central hypercapnic respiratory response induced by acute central
      administration of serotonin re-uptake inhibitor, fluoxetine.
AB  - Long-term neurochemical changes are responsible for therapeutic actions of
      fluoxetine. The role of increased central concentration of serotonin by
      inhibiting its re-uptake via fluoxetine on the central hypercapnic ventilatory
      response is complex and little is known. We aimed to research the effect of acute
      intracerebroventricular (ICV) injection of fluoxetine on hypercapnic ventilatory
      response in the absence of peripheral chemoreceptor impulses and the role of 5
      HT2 receptors on responses. Eighteen anesthetized albino rabbits were divided as
      Fluoxetine and Ketanserin groups. For ICV administration of fluoxetine and
      ketanserin, a cannula was placed in the left lateral ventricle by the stereotaxic
      method. Respiratory frequency (fR), tidal volume (V(T)) and ventilation minute
      volume (V(E)) were recorded in both groups. ICV fluoxetine (10.12 mmol/kg)
      injection during normoxia caused significant increases in V(T) and V(E) (both P <
      0.01) in the fluoxetine group. When the animals were switched to hypercapnia
      f/min, V(T) and V(E) increased significantly. The increases in percentage values
      in V(T) and V(E) in Fluoxetine + Hypercapnia phase were higher than those during
      hypercapnia alone (P < 0.01 and P < 0.05, respectively). On blocking of 5-HT2
      receptors by ketanserin (0.25 mmol/kg), the ventilatory response to Fluoxetine
      was abolished and the degree of increases in V(T) and V(E) in the Ketanserin +
      Hypercapnia phase were lower than those during hypercapnia alone (P < 0.01 and P
      < 0.001, respectively). We concluded that acute central fluoxetine increases
      normoxic ventilation and also augments the stimulatory effect of hypercapnia on
      respiratory neuronal network by 5-HT2 receptors in the absence of peripheral
      chemoreceptor impulses.

PMID- 22135916
TI  - Effects of human parvovirus B19 on expression of defensins and Toll-like
      receptors.
AB  - Both cell-mediated and humoral immunity have been widely investigated for the
      roles in pathogenesis of human parvovirus B19 (B19) infection. However, little is
      known about the effects of B19 infection on innate immunity. In the current
      study, expression of alpha-human neutrophil peptides (HNP) 1-3, alpha-human
      defensin (HD) 5, HD6, beta-human defensin (hBD)-1, hBD-3, toll-like receptor
      (TLR) 4, TLR5, TLR7 and TLR9 in B19-nonstructural protein (NS)-1 or B19-viral
      protein (VP)-2 transfected COS-7 cells was investigated by reverse transcription
      (RT)-PCR or by western blots. Significantly increased HNP1-3, HD5, HD6, hBD1 and
      hBD3 mRNA levels were detected at both 24 h and 20 days post-transfection in COS
      7 cells transfected with pEGFP-NS1. In pEGFP-VP2-transfected COS-7 cells,
      significantly increased HNP1-3, HD5, HD6, hBD-1 and hBD-3 mRNA expression levels
      were observed on day 20, albeit only hBD3 mRNA increased significantly at 24 h
      post-transfection. Additionally, TLR4, TLR5 and TLR7 proteins decreased
      significantly in COS-7 cells transfected with pEGFP-NS1 or pEGFP-VP2 at 48 h but
      significantly increased on day 20. Notably, only TLR9 protein increased
      significantly in the cells transfected with pEGFP-NS1 on day 20. No significant
      variation of TLRs was observed in cells transfected with pEGFP-NS1K334E, a single
      substitution mutantation of B19-NS1 protein without original cytotoxicity, at
      both 48 h and on day 20. These novel findings revealed the different effects of
      B19-NS1 and VP2 on the stimulation of defensins and TLRs and could provide a clue
      in understanding the roles of B19-NS1 and VP2 on innate immunity.

PMID- 22135917
TI  - [The role of Robben Island as a stock breeding station for the settlement at the
      Cape of Good Hope].
AB  - The universal notoriety of Robben Island as a penitentiary for political
      prisoners, notably in the 19th and 20th centuries, overshadows its previous
      historical significance established centuries ago. The Island, initially a source
      of seals and penguins to European mariners rounding the southern tip of Africa,
      and later for several other reasons, including its proximity to the Cape of Good
      Hope, played a pivotal role in the selection of this halfway station. The seals
      would provide blubber for train oil and the penguins, meat and eggs. The
      transhumant Peninsular Khoekhoe was to provide cattle and sheep by a barter
      process as before. Inconsistent access to Khoen livestock forced the Vereenigde
      Oost-Indische Compagnie (VOC) to consider their own breeding programmes and
      ultimately the establishment of Free Burgers. Van Riebeeck confirmed the
      suitability of Robben Island for the fattening and breeding of sheep and this
      island made a substantial contribution to the provision of sheep and mutton to
      the fleets and the local community. Khoen sheep did not do well in the Table
      Valley in early summer and it was expected that they would thrive on the drier
      island. Predators and stock theft were major problems at the Cape and neither
      occurred on the island. It is contended that it was unlikely that the settlement
      at the Cape would have occurred and succeeded without Robben Island.

PMID- 22135918
TI  - The sensitivity of direct faecal examination, direct faecal flotation, modified
      centrifugal faecal flotation and centrifugal sedimentation/flotation in the
      diagnosis of canine spirocercosis.
AB  - Several faecal examination techniques have shown variable sensitivity in
      demonstrating Spirocerca lupi (S. lupi) eggs. The objective of this study was to
      determine which faecal examination technique, including a novel modified
      centrifugal flotation technique, was most sensitive to diagnose spirocercosis.
      Ten coproscopic examinations were performed on faeces collected from 33 dogs
      confirmed endoscopically to have spirocercosis. The tests included a direct
      faecal examination, a faecal sedimentation/flotation test, 4 direct faecal
      flotations and 4 modified faecal centrifugal flotations. These latter 2 flotation
      tests utilised 4 different faecal flotation solutions: NaNO3 (SG 1.22), MgSO4 (SG
      1.29), ZnSO4 (SG 1.30) and sugar (SG 1.27). The sensitivity of the tests ranged
      between 42% and 67%, with the NaNO3 solution showing the highest sensitivity in
      both the direct and modified-centrifugal flotations. The modified NaNO3
      centrifugal method ranked 1st with the highest mean egg count (45.24 +/- 83), and
      was superior (i.e. higher egg count) and significantly different (P < 0.05)
      compared with the routine saturated sugar, ZnSO4 and MgSO4 flotation methods. The
      routine NaNO3 flotation method was also superior and significantly different (P <
      0.05) compared with the routine ZnSO4 and MgSO4 flotation methods. Fifteen per
      cent (n = 5) of dogs had neoplastic oesophageal nodules and a further 18% (n = 6)
      had both neoplastic and non-neoplastic nodules. S. lupi eggs were demonstrated in
      40% of dogs with neoplastic nodules only and 72.9% of the dogs with non
      neoplastic nodules. The mean egg count in the non-neoplastic group (61) was
      statistically greater (P = 0.02) than that of the neoplastic group (1). The
      results show that faecal examination using a NaNO3 solution is the most sensitive
      in the diagnosis of spirocercosis. The modified centrifugal flotation faecal
      method using this solution has the highest egg count. The study also found that
      dogs with neoplastic nodules shed significantly fewer eggs than dogs with non
      neoplastic nodules.

PMID- 22135919
TI  - In vitro antimicrobial susceptibility of Staphylococcus aureus strains from dairy
      herds in KwaZulu-Natal.
AB  - Staphylococcus aureus is 1 of the most important causes of bovine mastitis and is
      responsible for significant economic losses to the dairy industry worldwide. One
      of the principal approaches used in treating intramammary infections is the
      administration of antimicrobials. Due to the propensity of S. aureus to develop
      resistance, antimicrobial susceptibility monitoring is necessary to ensure that
      treatment regimens are effective. As part of this investigation, 90 S. aureus
      strains isolated from mastitis cases submitted to Allerton Provincial Veterinary
      Laboratory during 2008 and 2009 were evaluated for their susceptibility to a
      panel of 10 antimicrobials. Only 8 of the 90 S. aureus isolates tested (8.9%)
      were found to be susceptible to all of the antimicrobials evaluated. A very high
      level of resistance to the beta-lactam antibiotics was noted: 47.8% of the
      isolates were resistant to penicillin and 65.6% were resistant to ampicillin.
      Minimal resistance to oxacillin, cephalothin and trimethoprim-sulfamethoxazole
      (1.1%) was found. Seventeen (18.9%) of the isolates tested were found to be
      resistant to 3 or more antimicrobials. The need for vigilant monitoring of
      bacterial resistance trends in the dairy industry is warranted as the potential
      public health implications are significant.

PMID- 22135921
TI  - The utility of uric acid assay in dogs as an indicator of functional hepatic
      mass.
AB  - Uric acid was used as a test for liver disease before the advent of enzymology.
      Three old studies criticised uric acid as a test of liver function. Uric acid, as
      an end-product of purine metabolism in the liver, deserved re-evaluation as a
      liver function test. Serum totalbile acids are widely accepted as the most
      reliable liver function test. This study compared the ability of serum uric acid
      concentration to assess liver function with that of serum pre-prandial bile acids
      in dogs. In addition, due to the renal excretion of uric acid the 2 assays were
      also compared in a renal disease group. Using a control group of healthy dogs, a
      group of dogs with congenital vascular liver disease, a group of dogs with non
      vascular parenchymal liver diseases and a renal disease group, the ability of
      uric acid and pre-prandial bile acids was compared to detect reduced functional
      hepatic mass overall and in the vascular or parenchymal liver disease groups
      separately. Sensitivities, specificities and predictive value parameters were
      calculated for each test. The medians of uric acid concentration did not differ
      significantly between any of the groups, whereas pre-prandial bile acids medians
      were significantly higher in the liver disease groups compared with the normal
      and renal disease group of dogs. The sensitivity of uric acid in detecting liver
      disease overall was 65% while the specificity of uric acid in detecting liver
      disease overall was 59%. The sensitivity and specificity of uric acid in
      detecting congenital vascular liver disease was 68% and 59%, respectively. The
      sensitivity and specificity of uric acid in detecting parenchymal liver disease
      was 63% and 60%, respectively. The overall positive and negative predictive
      values for uric acid in detecting liver disease were poor and the data in this
      study indicated uric acid to be an unreliable test of liver function. In dogs
      suffering from renal compromise serum uric acid concentrations may increase into
      the abnormal range due to its renal route of excretion.

PMID- 22135920
TI  - Detection and characterisation of papillomavirus in skin lesions of giraffe and
      sable antelope in South Africa.
AB  - Papillomavirus was detected electron microscopically in cutaneous fibropapillomas
      of a giraffe (Giraffa camelopardalis) and a sable antelope (Hippotragus niger).
      The virus particles measured 45 nm in diameter. Histopathologically, the lesions
      showed histopathological features similar to those of equine sarcoid as well as
      positive immunoperoxidase-staining of tissue sections for papillomavirus antigen.
      Polymerase chain reaction (PCR) detected bovine papillomavirus (BPV) DNA. Bovine
      papillomavirus-1 was characterised by real-time PCR in the sable and giraffe, and
      cloning and sequencing of the PCR product revealed a similarity to BPV-1. As in
      the 1st giraffe, the lesions from a 2nd giraffe revealed locally malignant
      pleomorphism, possibly indicating the lesional end-point of papilloma infection.
      Neither virus particles nor positively staining papillomavirus antigen could be
      demonstrated in the 2nd giraffe but papillomavirus DNA was detected by real-time
      PCR which corresponded with BPV-1 and BPV-2.

PMID- 22135922
TI  - Determination of an optimal dose of medetomidine-ketamine-buprenorphine for
      anaesthesia in the Cape ground squirrel (Xerus inauris).
AB  - The optimal dose of medetomidine-ketamine-buprenorphine was determined in 25 Cape
      ground squirrels (Xerus inauris) undergoing surgical implantation of a
      temperature logger into the abdominal cavity. At the end of anaesthesia, the
      squirrels were given atipamezole intramuscularly to reverse the effects of
      medetomidine. The mean dose of medetomidine was 67.6 +/- 9.2microg/kg, ketamine
      13.6 +/- 1.9 mg/kg and buprenorphine 0.5 +/- 0.06 microg/kg. Induction time was
      3.1 +/- 1.4 min. This produced surgical anaesthesia for 21 +/- 4.2 min.
      Atipamezole 232 +/- 92 microg/kg produced a rapid recovery. Squirrels were
      sternally recumbent in 3.5 +/- 2.2 min.

PMID- 22135923
TI  - Pathology and immunohistochemistry of papillomavirus-associated cutaneous lesions
      in Cape mountain zebra, giraffe, sable antelope and African buffalo in South
      Africa.
AB  - Skin lesions associated with papillomaviruses have been reported in many animal
      species and man. Bovine papillomavirus (BVP) affects mainly the epidermis, but
      also the dermis in several species including bovine, the best-known example being
      equine sarcoid, which is associated with BVP types 1 and 2. This publication
      describes and illustrates the macroscopic and histological appearance of BPV
      associated papillomatous, fibropapillomatous or sarcoid-like lesions in Cape
      mountain zebra (Equus zebra zebra) from the Gariep Dam Nature Reserve, 2 giraffes
      (Giraffa camelopardalis) from the Kruger National Park, and a sable antelope
      (Hippotragus niger) from the Kimberley area of South Africa. An African buffalo
      (Syncerus caffer) cow from Kruger National Park also had papillomatous lesions
      but molecular characterisation of lesional virus was not done.
      Immunohistochemical staining using polyclonal rabbit antiserum to chemically
      disrupted BPV-1, which cross-reacts with the L1 capsid of most known
      papillomaviruses, was positive in cells of the stratum granulosum of lesions in
      Giraffe 1, the sable and the buffalo and negative in those of the zebra and
      Giraffe 2. Fibropapillomatous and sarcoid-like lesions from an adult bovine were
      used as positive control for the immunohistochemistry and are described and the
      immunohistochemistry illustrated for comparison. Macroscopically, both adult
      female giraffe had severely thickened multifocal to coalescing nodular and
      occasionally ulcerated lesions of the head, neck and trunk with local poorly
      circumscribed invasion into the subcutis. Necropsy performed on the 2nd giraffe
      revealed neither internal metastases nor serious underlying disease. Giraffe 1
      had scattered, and Giraffe 2 numerous, large, anaplastic, at times indistinctly
      multinucleated dermal fibroblasts with bizarre nuclei within the sarcoid-like
      lesions, which were BPV-1 positive in Giraffe 1 and BPV-1 and -2 positive in
      Giraffe 2 by RT-PCR. The sable antelope presented with a solitary large lesion
      just proximal to the right hind hoof, which recurred after excision, and was BPV
      1 positive by RT-PCR. Other wart-like growths were present elsewhere on the body.
      The Cape mountain zebra either succumbed from their massive lesions or were
      euthanased or removed from the herd because of them. The lesions were BPV-1
      and/or -2 positive by RT-PCR. The buffalo lesions were wart-like papillomatous
      projections in the inguinal and udder region. Stratum granulosum cells that
      stained immunohistochemically positive in the various species appeared koilocyte
      like, as described in human papillomaviral lesions.

PMID- 22135924
TI  - A survey of the prevalence of blowfly strike and the control measures used in the
      Ruens area of the Western Cape Province of South Africa.
AB  - Blowfly strike and the methods used to combat blowfly strike were recorded on 33
      properties in the Ruens area of South Africa during 2003/2004. Data were recorded
      on Merino and Dohne Merino hoggets (n = 4951) with at least 3 months' wool
      growth. The following data were captured: presence or absence of strike, site of
      the strike (body or breech), presence or absence of dermatophilosis as well as
      subjective scores for wool quality and wool colour. Control measures recorded
      include: chemical treatment (preventative and spot treatment), crutching,
      mulesing and the use of the Lucitrap system. Blowfly strike was not significantly
      influenced by gender or breed. Hoggets suffering from dermatophilosis were more
      likely to be struck, compared with contemporaries not suffering from the skin
      disorder (0.057 vs 0.027; P < 0.05). Merino hoggets generally had higher scores
      than their Dohne Merino contemporaries for wool quality (32.6 vs 27.4; P < 0.05)
      and wool colour (29.0 vs 27.2; P < 0.05). There was an indication that the
      Lucitrap system may have reduced flystrike, but the effect was not statistically
      significant (P = 0.19 for overall strikes and P = 0.12 for body strike). The
      Mules operation benefited overall flystrike (0.013 vs 0.110; P < 0.05); mainly
      through an effect on breech strike (0.010 vs 0.109; P < 0.05). The proportion of
      fly strikes increased with wool length, and declined with an increase in farm
      size in wool colour score. None of the ethically acceptable control measures
      assessed could substantially reduce blowfly strike on their own, and an
      integrated pest management programme was proposed.

PMID- 22135925
TI  - Nicotiana glauca poisoning in ostriches (Struthio camelus).
AB  - Putative Nicotiana glauca (wild tobacco) poisoning was diagnosed in a flock of
      ostriches near Oudtshoorn, South Africa. Post mortem examinations (n = 7) were
      performed on ostriches (Struthio camelus) that had died. Suspicious leaf remnants
      (weighing 80-770 g), packed in a layer on top of other plant material, were
      carefully separated from the proventricular content and submitted for chemical
      determination of anabasine, the major toxic principle contained by this plant. A
      standard solid phase extraction method was used followed by an optimised liquid
      chromatography-mass spectrometry procedure. Anabasine was detected in the leaf
      remnants (114-177 microg/g dry weight) removed from the proventriculus of the
      ostriches that succumbed as well as in control N. glauca leaves (193 microg/g dry
      weight). The analytical methods used in this study revealed the presence of
      anabasine in the suspicious leaf remnants, indicating that the birds had been
      exposed to N. glauca and had died of this poisoning.

PMID- 22135926
TI  - Bilateral multiple cystic kidney disease and renal cortical abscess in a
      Boerboel.
AB  - Cystic renal disease is rare in dogs and although infected renal cysts have been
      reported in humans, no report could be found in dogs. A 58 kg, 5-year-old,
      castrated, male Boerboel presented with weight loss, pyrexia, lethargy and
      vomiting, 20 months after an incident of haematuria was reported. The initial
      ultrasonographic diagnosis was bilateral multiple renal cysts of unknown
      aetiology. The cysts had significantly increased in size over the 20-month period
      and some contained echogenic specks which could be related to infection, normal
      cellular debris or haemorrhage. In both kidneys the renal contours were distorted
      (the left more than the right). The abnormal shape of the left kidney was largely
      due to multiple cysts and a large crescent-shaped septate mass on the cranial
      pole of the kidney. Aspirates of the septate mass were performed (left kidney)
      and the cytology and culture were indicative of an abscess. It is suggested that
      the previous incident of haematuria provided a portal of entry for bacteria into
      the cysts resulting in renal cortical abscess formation.

PMID- 22135927
TI  - Contrast-enhanced computed tomography angiography and volume-rendered imaging for
      evaluation of cellophane banding in a dog with extrahepatic portosystemic shunt.
AB  - A 4-year-old, 1.8 kg, male, castrated Maltese was presented for evaluation of
      urolithiasis. Urinary calculi were composed of ammonium biurate. Preprandial and
      postprandial bile acids were 44.2 and 187.3 micromol/l, respectively (reference
      ranges 0-10 and 0-20 micromol/l, respectively). Single-phase contrast-enhanced
      computed tomography angiography (CTA) with volume-rendered imaging (VRI) was
      obtained. VRI revealed a portocaval shunt originating just cranial to a tributary
      of the gastroduodenal vein and draining into the caudal vena cava at the level of
      the epiploic foramen. CTA revealed a 3.66 mm-diameter shunt measured at the level
      of the termination of the shunt and a 3.79 mm-diameter portal vein measured at
      the level between the origin of the shunt and the porta of the liver. Surgery was
      performed using cellophane banding without attenuation. Follow-up single-phase
      CTA with VRI was obtained 10 weeks after surgery. VRI revealed no evidence of
      portosystemic communication on the level of a cellophane band and caudal to the
      cellophane band. CTA demonstrated an increased portal vein diameter (3.79-5.27
      mm) measured at the level between the origin of the shunt and the porta of the
      liver. Preprandial and postprandial bile acids were 25 and 12.5 micromol/l,
      respectively (aforementioned respective reference ranges), 3 months post-surgery.
      No problems were evident at 6 months.

PMID- 22135928
TI  - Should veterinarians consider acrylamide that potentially occurs in starch-rich
      foodstuffs as a neurotoxin in dogs?
AB  - Three clinically healthy Labrador puppies developed ataxia, hypermetria and
      convulsions shortly after eating the burnt crust of maize porridge. Two of the
      puppies died. Acrylamide toxicity was considered based on the history of all 3
      puppies developing nervous signs after being exposed to a starch-based foodstuff
      that was subjected to high temperature during preparation. Acrylamide-induced
      neurotoxicity is thought to partially result from a distal axonopathy.

PMID- 22135929
TI  - Variability of yellow tulp (Moraea pallida Bak.) toxicity.
AB  - Yellow tulp (Moraea pallida Bak.), collected predominantly during the flowering
      stage from a number of sites in South Africa, showed large variation in digoxin
      equivalent values, indicating variability in yellow tulp toxicity. Very low
      values were recorded for tulp collected from certain sites in the Northern Cape.

PMID- 22135930
TI  - [The right to receive care to die with dignity].

PMID- 22135931
TI  - [Vaccines. Official calendar of vaccinations in the infancy and the adolescence].
AB  - Vaccines are a key tool in disease prevention and public health. Its application
      through a vaccination schedule, which displayed what vaccinations and at what age
      should be given, it is irreplaceable for a high coverage. Nurses, working in a
      multidisciplinary manner are essential for successful implementation of
      vaccination programs.

PMID- 22135932
TI  - [Responsibility versus informed consent nurse].
AB  - In recent years we have witnessed a quick development in concern and research
      about informed consent in the biomedical field. This development has taken place
      mainly due to the increased importance given within the medical field to the
      patient's autonomy as well as law ratified legally recognized and regulated in
      our country in law 41/2002 of patient autonomy However, in the field of nursing
      is not even clear what the role of professional nursing with regard to informed
      consent, or what its responsibilities in this regard. Therefore, the objective of
      this study is to clarify what is the responsibility of nursing in relation to the
      CI. In addition, we discuss the relevance or otherwise of the implementation of
      informed consent documents for nursing care, addressing both its advantages and
      disadvantages.

PMID- 22135933
TI  - [Generic medications, yes, but not at any price].

PMID- 22135934
TI  - [Morbid obesity].
AB  - Morbid obesity (MO) is a serious disease caused by genetic and environmental
      factors, which is associated with multiple comorbid factors that impact very
      significantly on the amount and life quality. Obesity surgery is a complex
      surgery but not without complications, which objective is to achieve an ideal
      weight or cure obesity reducing comorbidities and improving the welfare of
      patients. The Spanish Society for the Study of Obesity (SEED) and the Spanish
      Society of Obesity Surgery (SECO) have developed a consensus document that allows
      the various professionals involved in the treatment of OM practical guidance in
      developing their own protocols in their work environment. In this context, the
      general and digestive service of the HUB team developed the clinical course of
      this surgical procedure because it is a tool that facilitates systematic care and
      multidisciplinary group of patients with a predictable clinical course, such as
      whether morbidly obese patients operated by laparotomy or laparoscopy.

PMID- 22135935
TI  - [Therapeutic uses of ortho-podiatry in the diabetic foot].
AB  - The neuropathic diabetic foot ulcers are a major public health problem given by
      different situations: the chronic nature of the injury, a low response to
      treatment, relapse rates, etc. Therefore pose a serious personal, family health
      and social, with a significant expenditure of human and material resources.
      Treatment requires a multidisciplinary team which integrates a podiatrist as part
      of it. He will address especially the pre-ulcers, and have a singular care in
      diabetic foot by treatment with orthosis. Since your question can be seen changes
      in the feet of diabetic patients could be treated on an outpatient basis.

PMID- 22135936
TI  - [Abuse in the elderly].
AB  - Reflections on the UN decree of June 15 as International Day of No Abuse of the
      Elderly which have been enhanced by the celebration in Madrid, Hospital Clinico
      San Carlos, a day devoted to this topic with the aim of raising awareness among
      professionals working in health centers and other interest groups, groups of
      retirees and social services, health problems and abuse in the elderly

PMID- 22135937
TI  - [Endoscopic transvaginal cholecystectomy].
AB  - INTRODUCTION: Transluminal endoscopic surgery through natural orifices (NOTES)
      allows intraperitoneal surgical procedures with minimal access to the abdominal
      wall. Currently it is not yet possible to perform these interventions without
      laparoscopic assistance, so these procedures are hybrids, fusion of
      minilaparoscopy and transluminal endoscopic surgery We present a prospective
      clinical series of patients undergoing surgery for gallstones, with hybrid NOTES
      transvaginal cholecystectomy with a nursing care plan adapted to this new
      approach. METHODS: Prospective clinical series of consecutive patients,
      nonrandomized, with transvaginal NOTES cholecystectomy. The surgery was performe
      with the assistance of two parietal entryports, one of umbilical 5 mm and 3 mm
      right upper quadrant of the abdomen. Analysis of nursing care plan with
      particular attention to safety of the procedure parameters and anxiety associated
      to the surgery RESULTS: There were no serious systemic complications. The main
      problem with this type of surgery is the fear of patients in relation to the new
      ways for a non-gynecological transvaginal procedures as ckolecystectomy and the
      risk of vaginal bleeding and urinary infection. DISCUSSION: Hybrid transvaginal
      cholecystectomy is a good surgical model of minimally invasive surgery. Its
      implementation is possible in groups with habit laparoscopic surgery, using
      standard instrumentation of endoscopy and laparoscopic surgery. The surgical
      team, doctors and nurses, must be well prepared for this new approach, because
      special and innovative cares are demanded.

PMID- 22135938
TI  - [A study on surgical dressings and the uses associated to them].
AB  - OBJECTIVE: To identify the variability in the surgical dressing practices and to
      assess the factors of their use. METHOD: A prospective study on surgical
      dressings was carried out. Data was collected on some post surgery patients who,
      once outside the operating room in a general hospital, they were still wearing a
      surgical dressing. A non-random sample was included. Socio demographic data, pre
      operative and intra operative data inside the operating room were collected as
      well as post surgical tests in the surgical inpatient wards. Tests chi2 were
      carried out for the category variables, tau Student for the continuous ones and
      the variant analysis. RESULTS: 315 patients were put into groups of 5 according
      to the surgical proceedings. All dressings were realized with non-woven gauze
      dressings (more absorbent) and mostly removed every 24 to 48 hours. Two groups
      showed more exuded dressings. The highest percentage of lesions appeared when
      dressings were removed between 24 and 48 hours. 50% of the removed ones before
      the first 24 hours had been over dressed and the chance of having skin lesion was
      increased 7 times with the reinforcement. Patients showed a medium average of
      comfort of 6,09 (EVA 0-10) to the dressings. CONCLUSIONS: The use of the
      traditional dry dressings to cover surgical wounds and the technique to apply a
      dressing over the existing one are here confirmed. A direct relation is observed
      between the reapplication of dressings to the same wound and the skin lesions.

PMID- 22135939
TI  - [Educating children means to lead out of... Interview by Maria Jesus Nadal
      Nadal].

PMID- 22135940
TI  - [Nursing care in the neurosurgical patient].
AB  - The Neurosurgery patient is the one who has been undergone to surgery in the
      brain or in the peripheral nervous system, and might suffer complications during
      per operative period. They are patients who require attention in areas
      specialized in critical health care and who will need advanced monitorization,
      due to it is a high risk postoperative. It is in this point, in the one in which
      the nurse develops a function of vital importance in the health care, through the
      constant and specialized attention, to get the best quality of health care. The
      nurse should be able to evaluate, prevent, control and identify risk situations,
      avoiding complications and helping patient recovery

PMID- 22135941
TI  - Body weight maintenance and levels of mutans streptococci and lactobacilli in a
      group of Swedish women seven years after completion of a Weight Watchers' diet.
AB  - The long-term effect of the WW programme on weight and oral cariogenic bacteria
      was evaluated after 7 yr. All WW who completed the 8-wk dietary regimen in an
      earlier study (n=33) and the persons in the reference group (REF) (n=27) were
      invited to participate. The salivary secretion rate, numbers of mutans
      streptococci (MS) and lactobacilli (lbc) were determined. The WW were weighed.
      Sustaining a 5% weight loss from the initial weight was regarded as successful
      weight maintenance. An interview according to a standardised questionnaire was
      conducted on medication,the intake of antimicrobial agents, dietary changes and
      experience of dental caries during the last 7 yr. 25 WW and 21 REF qualified to
      participate. On a group basis, weight, salivary MS and lbc displayed pre-diet
      levels after 7yr. 15 of the WW (60%) were below their initial weight. Successful
      weight maintenance was achieved by 32%. Reported changes in the intake of fat
      rich products differed significantly between the WW and the REF. Nine WW reported
      fewer carious lesions after joining the WW. Ninety per cent of REF did not regard
      caries as a problem. Comparisons of pre- and post-diet data and 7 yr data
      indicated short-term compliance and varying outcome in terms of long-term
      compliance. No association was found between salivary levels of bacteria and long
      term weight maintenance on a group basis. However,further well-designed
      longitudinal studies are required to confirm whether salivary MS could be used on
      an individual basis to validate reported sucrose intake in a dietary regimen.

PMID- 22135942
TI  - Clinical evaluation of fixed partial dentures made in Sweden and China.
AB  - The aim of this study was to compare the quality of fixed partial dentures (FPDs)
      made in a Chinese dental laboratory with corresponding FPDs made in Swedish
      dental laboratories. Twenty-one patients were fitted with FPDs between March 2007
      and December 2008. Single crowns and prostheses of up to seven units were made.
      All dentures, gold and CoCr alloys covered with ceramic, were produced in
      duplicate: one by a dental technician in China and the other by a dental
      technician in Sweden. The dentures were blind-tested with regard to marginal
      integrity, anatomic form and color, approximal and occlusal contacts, and time
      taken for adjustments. The composition of dentures was analyzed, and the material
      used, framework weight, compliance of the laboratories, and costs (material and
      labour) were recorded. There was no difference in the quality of marginal
      integrity, anatomic form, color, approximal and occlusal contacts, or in the time
      taken for adjustments. The bridge frameworks made in China were thinner and
      lighter (p<0.01) than those made in Sweden. Three FPDs from China showed elastic
      deformation when tested clinically and were considered too thin for clinical use.
      In 11 out of 14 orders from the Chinese laboratory, the gold alloy specified was
      not delivered and the cobalt-chromium alloy contained small amounts (0.19%) of
      nickel.The prostheses with gold-alloy frameworks from China cost 47% of those
      from Sweden (p<0.01) and those with cobalt/chromium frameworks 44% (p<0.01). In
      conclusion, the quality of the FPDs made in Sweden and China was comparable, with
      the exception of the dimension of the Chinese bridges, which in some cases was
      considered too weak. The gold alloy ordered from the Chinese laboratory was often
      not the alloy delivered and the CoCr alloy contained small amounts of nickel.
      FPDs from China cost less than half the price of those from Sweden.

PMID- 22135943
TI  - Frequent jaw-face pain in chronic Whiplash-Associated Disorders.
AB  - Chronic Whiplash-Associated Disorders (WAD) present with frequent pain in the
      neck, head and shoulder regions but the presence of frequent jaw-face pain is
      unclear. The aim of the study was to investigate the frequency of jaw-face pain,
      pain in other regions, and general symptoms in chronic WAD patients. Fifty
      whiplash-patients and 50 healthy age- and sex-matched controls were examined by
      questionnaire for pain in the jaw-face, pain in other regions and other symptoms.
      In contrast to healthy, a majority of the WAD patients (88%) reported frequent
      pain in the jaw-face, in addition to frequent pain in the neck (100%), shoulders
      (94%), head (90%) and back (72%). The WAD patients also reported stiffness and
      numbness in the jaw-face region, and frequent general symptoms such as balance
      problems, stress and sleep disturbances. The result suggests that frequent pain
      in the jaw-face can be part of the spectrum of symptoms in chronic WAD.The
      finding of self-reported numbness in the jaw-face indicates disturbed trigeminal
      nerve function and merits further investigation. We conclude that assessment of
      WAD should include pain in the jaw-face region. A multidisciplinary
      rehabilitation program including dentists, preferably specialized in the area of
      orofacial pain, should be advocated after whiplash injury.

PMID- 22135944
TI  - Patients' adherence to hard acrylic interocclusal appliance treatment in general
      dental practice in Sweden.
AB  - The aims of the present study were to investigate patient adherence to treatment
      with hard acrylic interocclusal appliance in general dentistry in Sweden and to
      see if some general factors could predict patient adherence or non-adherence.
      During the period January - May 2009 a postal questionnaire was sent to all adult
      patients (> or = 20 years of age) that had received a hard acrylic interocclusal
      appliance from the public dental health service in the County of Uppsala during
      2007 (n=388). The same questionnaire was also sent to all adult patients that had
      received a hard acrylic interocclusal appliance at a specialist clinic during the
      same year (n=69). The response rate in general dental practice was 71% and at the
      specialist clinic the response rate was 91%. In general dental practice, 97% of
      the hard acrylic interocclusal appliances were stabilisation appliances. At the
      specialist clinic other types of interocclusal appliances was used to a greater
      extent. A vast majority of patients in both general dental practice and at the
      specialist clinic experienced that the interocclusal appliance had a positive
      treatment effect. In general dental practice, 73% of the patients still used
      their interocclusal appliances 1 1/2-2 years after they had received them. The
      corresponding figure at the specialist clinic was 54%. The main reasons for not
      using the interocclusal appliance, besides disappearance/reduction of TMD
      symptoms, were different kinds of comfort problems. From the results of this
      study it is concluded that the patient adherence to hard acrylic stabilisation
      appliances made in general dental practice in Sweden is good. It can also be
      concluded that a perceived good treatment effect, as well as treatment of more
      long-term conditions, predicted a better patient adherence to hard acrylic
      stabilisation appliances. More studies concerning factors affecting patient
      adherence in TMD therapy are warranted.

PMID- 22135945
TI  - SEITO - Stockholm Eastman Index of Treatment Outcome.
AB  - To obtain high quality in orthodontics; it is important to evaluate the
      treatment. There are many indices for evaluation of treatment outcome however all
      of them compare treatment outcome with ideal occlusion. Therefore Stockholm
      Eastman Index of Treatment Outcome (SEITO) was invented. This index relates the
      treatment outcome to the treatment goal. SEITO is a morphological index based on
      criteria from the records including study casts, and/or intra oral photos.
      METHOD: The outcome of treatment is related to the treatment goal as stated in
      the records. Pre-treatment goals are divided into subgroups; overjet, vertical
      relation anterior/lateral), anterior cross bite, transverse relations, impacted
      teeth and space crowding/ spacing. Each subgroup is scored; the points are 0, 1,
      3 or 5 depending on the severity of the malocclusion. The points for each
      subgroup are added to give a total sum of treatment goal points. Each post
      treatment subgroup above is evaluated. If the treatment goal is fulfilled, the
      treatment outcome points are equal to the treatment goal points. If not - there
      is a reduction in the outcome points. Finally the outcome points are expressed as
      a percentage of the treatment goal points and form a measure of the success of
      treatment. CONCLUSION: SEITO index is a simple and quick way to obtain a picture
      of the quality of treatment outcome, and the only orthodontic index that relates
      the treatment outcome to the treatment goal.

PMID- 22135947
TI  - Characteristics of patients referred for Cone Beam Computed Tomography (CBCT) of
      ectopically erupting maxillary canines.
AB  - The aim was to study the characteristics of patients referred for tomographic
      examinations of maxillary canines suspected of ectopic eruption and evaluate
      whether the criteria used for referring the patients could be considered
      appropriate. During a 1-year-period all patients (n=63) referred for tomographic
      examinations of ectopically erupting maxillary canines, when intra-oral x-ray
      examinations were insufficient to describe the position of the canine and the
      conditions at adjacent teeth, were examined by means of Cone Beam Computed
      Tomography (CBCT). There was a statistically significant overrepresentation of
      girls (63.5%) among the referred patients. The mean age for the girls was 146.0
      +/- 22.2 months and for the boys 151.8 +/- 17.8 months, a statistically non
      significant difference. In total, 91 maxillary canine sites were examined and in
      33 of the examined sites (36%) a resorption was found in the root surface of an
      adjacent tooth, in the vast majority the lateral incisor. Since more than one
      tooth was occasionally affected the total number of resorptions was 38 of which
      14 had reached the pulp (37%). Considering the frequency of teeth, adjacent to
      ectopically erupting maxillary canines, that were affected by resorptions it can
      be concluded that the referral criteria used were appropriate. Given theyoung age
      of the patients it can be recommended that tomography should be performed with
      CBCT techniques that permit the examination of small volumes and result in high
      quality images.

PMID- 22135946
TI  - Esthetic views on facial and dental appearance in young adults with treated
      bilateral cleft lip and palate (BCLP). A comparison between professional and non
      professional evaluators.
AB  - The aim of the present study was to make a comparison between the professional
      and non-professional evaluations concerning the esthetic outcome after the
      completion of patients who have been treated for bilateral cleft lip and palate.
      A web-based questionnaire, with 12 photo sets, was answered by 25 orthodontists
      and 20 young adults who had been treated with orthodontic fixed appliances. They
      ranked the three first features they noticed when looking at each photo set, and
      then rated specific variables as being bad, fairly good, good, or excellent. At
      the end of each set, they had an opportunity to add any additional comments. The
      three features first noticed by the orthodontists were 'the upper lip', 'the
      nose' and 'the scar'. The young adults reported first 'the teeth', 'the upper
      lip' and 'occlusion/alignment of the teeth'. The specific variables similarly
      rated by orthodontists and young adults were 'the profile of the face', 'the form
      of the upper lip' and 'the entire facial appearance'. The orthodontists were less
      critical than the young adults concerning 'the upper teeth alignment', 'the lower
      teeth alignment', 'shape of the upper teeth', and 'color of the upper teeth'. The
      individual opinion on each separate set of photos was additionally important in
      explaining the rating, regardless the category of being either orthodontists or
      young adults.

PMID- 22135948
TI  - Unmanaged Risk in the Gulf.

PMID- 22135949
TI  - Protection from whatever they face.

PMID- 22135950
TI  - Hazard recognition training to prevent future failures.

PMID- 22135951
TI  - Filling the manager's toolkit.

PMID- 22135952
TI  - Ready to run.

PMID- 22135953
TI  - Family ties. Interview by Jerry Laws.

PMID- 22135954
TI  - Stay healthy on the job this cold & flu season.

PMID- 22135955
TI  - Cut performance levels and testing.
AB  - While the ISEA performance levels and general recommendations detailed above can
      help tp provide guidance when selecting hand protection products, the
      responsibility for testing products for specific end-user applications still
      rests with the end user. We can indicate, for example, that a medium-weight,
      uncoated Kevlar glove will typically have an ISEA cut rating of 3, but we cannot
      say the glove will provide the level of protection needed for the range of jobs
      on an automobile assembly line. Another Level 3 glove might be better suited to
      an application the require the worker to have an oil grip. As glove
      manufacturers, we know gloves. We do not know the details about every workplace.
      We therefore, must look to our customers to provide us the properties they need
      for hand protection products that will sufficiently protect their workers on the
      job.

PMID- 22135956
TI  - Protecting the past, securing the future.

PMID- 22135957
TI  - The real story behind AED failures.

PMID- 22135958
TI  - 12-step leadership.

PMID- 22135960
TI  - Ending costly mandatory detention for asylum seekers.

PMID- 22135959
TI  - Nurses' and midwives' EB8: strengthening nursing and midwifery.

PMID- 22135961
TI  - [At the gates of Paris, tuberculosis].

PMID- 22135962
TI  - [Excision and other sexual mutilations. Between culture and abuse].

PMID- 22135963
TI  - [Systemic mastocytosis. Osteoporotic fracture as a manifestation].

PMID- 22135964
TI  - [Risk of reactivation or exacerbation of an infectious disease during iatrogenic
      immunosuppression or immune reconstitution].
AB  - Drug induced immunosuppression increases the risk of infections, both occurring
      as reactivation of latent-infections and occurrence of recent opportunistic ones.
      Thus, a careful mandatory infection screening is needed before immunosuppressive
      drugs onset. In addition, immune reconstitution after immunosuppression cessation
      can be associated with acute worsening of the underlying infection leading to the
      immune reconstitution inflammatory syndrome that must be differenciated from
      infection recurrences, relapses or resistance to antiinfective agents.

PMID- 22135965
TI  - [Dorsal meningioma].

PMID- 22135966
TI  - [Cutis marmorata telangiectatica congenita].

PMID- 22135967
TI  - [Pneumonia is the leading cause of death of infectious origin].

PMID- 22135968
TI  - [Epidemiology and mechanisms of pneumonia in adults].
AB  - Pneumonia is a major cause of morbidity and mortality in France. Microbial
      epidemiology, profile of bacterial resistance and prognosis depend on the type of
      pneumonia (community acquired pneumonia [CAP], health-care associated pneumonia,
      hospital acquired pneumonia or ventilator associated bacterial pneumonia).
      Streptococcus pneumoniae, community respiratory viruses, Mycoplasma pneumoniae,
      Chlamydia pneumonia and Legionella sp. are the five most common pathogens causing
      CAP in adults. The susceptibility of these four bacteria to antibiotics used in
      the management of CAP remains stable over time. Comorbidities, risk factors or
      impairment of the host defence mechanisms changes the microbial classic
      epidemiology of CAP. Patients with health care-associated pneumonia have an
      increased risk of multidrug-resistant bacteria, initial inappropriate
      antimicrobial treatment, severity and mortality, due to a different microbial
      epidemiology from those of CAP.

PMID- 22135969
TI  - [Alterations of mechanical and immune host defenses causing pneumonia: the case
      of recurrent pneumonia].

PMID- 22135970
TI  - [When to ask a microbiological diagnostic test in pneumonia and how to interpret
      the results].
AB  - Pneumonia is a leading cause of death in adults in the industrialised countries
      and in the rest of the world in infants. Most of the time the pathogens stay
      unkown and the current recommendations for the treatment of pneumonia are mainly
      based on a severity score to adapt the treatement to the risk. Nonethless new
      pathogens have recently been identified, coronavirus for SRASS, H5N1 for avian
      Flu, N1N1 for pandemic Flu, 35 years after the identification of Legionella
      pneumophila. These exemples stress the necessity to do and continue to identify
      pathogens in these clinical situations. Those last years new diagnostic tests
      have been elaborated: antigen detection in urines or in nasopharyngeal samples,
      molecular methods allowing to look at one or several pathogens at the same time
      on a single sample (Multiplex) with an increased sensitivity with regard to the
      more classical methods. Indirect methods have been developed to quantify
      inflammation in correlation with a bacterial or not infection. All these tests
      contribute to a better understanding but can and/or could be used in new
      algorithms to treat patients with pneumonia.

PMID- 22135971
TI  - [Biological markers and antigen tests for pneumonia].

PMID- 22135972
TI  - [Community-acquired pneumonia in adults].
AB  - Community-acquired pneumonia are potentially life threatening infections for
      which accurate diagnosis and adequate antibiotic treatment are mandatory. S.
      pneumoniae remains the first bacterial agent and, is responsible, with L.
      pneumophila of most of fatal issues. Analysis of risk factors and severity signs
      by practitionners is required to properly manage such infections, Microbiological
      documentation is scarce in ambulatory medecine and account for less than 50% of
      hospitalised patients; thus, antibiotic treatment is empirical in most of cases.
      Amoxicillin remains drug of choice for ambulatory or hospitalized patients
      without risk factors or severity signs in medical wards, pristinamycin is
      recommended when an atypical agent cannot be rule out. Respiratory quinolone,
      mainly levofloxacin, can be prescribed in high risk patients, or in case of a
      failure of a first line of treatment.

PMID- 22135973
TI  - [Management of pneumonia in the elderly].
AB  - Pneumonias in elderly are frequent and severe. They require an accurate
      assessment following clinical, biological and radiological steps. Each of them
      can contribute to give answers to the following questions: does this patient need
      emergency hospitalisation? Is the infection really bacterial and pulmonary?
      Should antibiotics be started? Which others treatments should be associated for
      the infection itself and for comorbid conditions? Concerning prevention, every
      effort must be done to decrease the incidence of these infections, especially
      vaccination. Pulmonary infections in nursing home need specific attention:
      cumulation of bad prognosis factors, risk of epidemic propagation, and
      vaccination of all people caring patients when required.

PMID- 22135974
TI  - [When pneumonia does not respond to antibiotic therapy].
AB  - The favorable pneumonia outcome with antibiotics according to the recommendations
      is defined by improving clinical symptoms in 48-72 hours followed by their
      normalization within less than 10 days. This is different to stop progression of
      radiological abnormalities that can be delayed for 48-72 hours and moreover to
      radiological normalization which may require 4 to 8 weeks. The non favorable
      outcome, 48-72 hours after a first line of antibiotic therapy results in the vast
      majority of cases, from an infection: the pneumonia is not or poorly treated. The
      non favorable outcome 5-6 days after two successive lines of antibiotic therapy
      may also result from a non infectious cause: immunologic, toxic or tumoral
      pneumonitis. Practitioner dilemna is not to worry too early (slow-resolving
      pneumonia with clinical cure in normal time but slow radiological resolution) or
      too late (non-resolving pneumonia with no clinical cure and persistence or
      radiological extension).

PMID- 22135976
TI  - [Precision in PubMed/MEDLINE].

PMID- 22135977
TI  - [Management of hypercholesterolemia: what target for LDL cholesterol?].
AB  - Low-density lipoprotein cholesterol (LDL-c) concentration is an independent
      cardiovascular risk factor, which mostly contributes to the development and
      progression of atherosclerosis. Results of randomized clinical trial with statins
      demonstrate that the optimal LDL-c target is < 70 mg/dL. The physiological range
      of LDL-c in hunter-gatherers and wild mammals, who do not develop
      atherosclerosis, is 0.5 to 0.7 g/L. No major safety concern was found in human
      with genetically-related low levels of LDL-c. A moderate increase in haemorrhagic
      stroke and diabetes was found in some trials with statins. Guidelines recommend
      to modulate the LDL-c target according to the level of the total cardiovascular
      risk.

PMID- 22135975
TI  - [Pneumonia in the immunocompromised patient].
AB  - Immunosuppression occurs as a result of neutropenia (neutrophil count < 500/mm3),
      cellular immunodeficiency (CD4 lymphocyte count < 200/mm3) and humoral
      immunodeficiency (hypogamma- or dysglobulinemia), Immunocompromised patients are
      susceptible to infection and the lung is one of the most commonly affected
      organs. Bacterial pathogens are seen in the three types of immunodeficiency.
      Prolonged neutropenia of more than 7 days is associated with fungal infection and
      particularly with invasive aspergillosis. Cellular immunodeficiency is associated
      more frequently with tuberculosis and Pneumocysti jiroveci pneumonia. Diagnosis
      approach begins with looking for historical clues (immunodeficiency type,
      exposure...). Computed tomography features are often useful with some suggestive
      abnormalities (i.e. halo sign and invasive aspergillosis). Bronchoalveolar lavage
      is the key to microbiologic diagnosis. Hospitalization is required in most cases.
      Antimicrobial therapy must be introduced quickly because delayed therapy is
      responsible for increased mortality. Empirical treatment is used initially until
      specific microbiological data are available.

PMID- 22135978
TI  - [Screening for familial hypercholesterolemia].

PMID- 22135979
TI  - [Hypertriglyceridemia: therapeutic strategy].
AB  - Causes of hypertriglyceridemia (HTG) vary according to their severity and to
      their character pure or mixed. Environmental factors including caloric intake
      excess, fructose overload, alcohol consumption, metabolic syndrom, diabetes, and
      drug exposure are mostly involved in pure, mild HTG. In contrast, the main
      etiology of mixed HTG (combined dyslipidemia) is familial combined hyperlipidemia
      which is commonly associated with metabolic syndrome. Major HTG (> 10 g/L)
      results mostly from genetic disorder in lipid metabolism with a variable
      contribution of environmental factors. The complications of HTG are an increased
      risk of acute pancreatitis (TG > 10 g/L) and a controversial atherogenic risk.
      Lifestyle modification is the treatment cornerstone. Nevertheless, statins are
      generally considered as the first drug if a medication is necessary for mixed
      hyperlipidemia. Fibrates may be used in combination with statin for patient with
      high atherogenic risk and simultaneous residual hypertriglyceridemie and low HDLc
      or in high risk patient with severe pure hypertriglyceridemia.

PMID- 22135980
TI  - [What about HDL cholesterol?].
AB  - Epidemiological and clinical intervention data have consistently shown that low
      levels of HDL-cholesterol (HDL-C) are associated with an increased risk of
      cardiovascular disease. In contrast, data for gene variants associated with
      changes in HDL-C are more conflicting, potentially reflecting the complexity of
      HDL metabolism. Indeed reverse cholesterol transport and HDL functionality cannot
      be appreciated by HDL-C level alone. In clinical practice, low HDL-C is
      frequently combined with other metabolic abnormalities, particularly with type 2
      diabetes, metabolic syndrome and abdominal obesity. These circumstances are
      usually associated with the presence of an atherogenic dyslipidemia characterized
      by the lipid triad low HDL-C, elevated triglycerides and excess of small dense
      LDL particles. The first step in the management of low HDL-C is lifestyle
      interventions: weight loss, physical activity and smoking cessation are effective
      in increasing HDL-C. The residual cardiovascular risk among high risk patients
      who are treated with statins, have triggered intense interest in therapies
      raising HDL-C. Until now, nicotinic acid is the most effective drug. All the new
      therapeutic strategies acting on HDL should be validated by cardiovascular
      clinical trials.

PMID- 22135981
TI  - [Statins in the management of dyslipidemias].
AB  - Statins, combined with life-style advices, have a key position in the prevention
      of cardiovascular diseases. By inhibiting HMG-CoA reductase enzyme, these
      medications reduce total and LDL cholesterol levels in a dose-dependent manner.
      They also exert various pleiotropic effects that may contribute to the
      cardiovascular protection. Although some differences exist between available
      statins, a class effect seems predominant. Statins have proven their efficacy in
      numerous controlled randomized trials (recently pooled in meta-analyses), both in
      primary and secondary prevention, including various specific populations, among
      them patients with diabetes. Tolerance and safety profile is rather good even if
      muscular and hepatic adverse events may occur. The prescription of statins should
      target high-risk individuals and both therapeutic inertia and drug non-compliance
      should be avoided.

PMID- 22135982
TI  - [Alternative drugs to statins].

PMID- 22135983
TI  - [Payment-for-performance].

PMID- 22135984
TI  - [Sudden onset sensorimotor deficit: first consider stroke].

PMID- 22135985
TI  - [Acute pericarditis: a not so simple question].

PMID- 22135986
TI  - [Height and weight delay in growth].

PMID- 22135987
TI  - [Acute renal failure. Anuria].

PMID- 22135988
TI  - [Angina pectoris and myocardial infarction].

PMID- 22135989
TI  - [Renal tumors].

PMID- 22135990
TI  - [Kidney transplantation. The creative contribution of Rene Kuss and Jean
      Hamburger].

PMID- 22135991
TI  - [Culture trap].

PMID- 22135992
TI  - [Muslim diabetes patients. No reason to be afraid!].

PMID- 22135993
TI  - [Culture sensitive nursing requires flexible solutions (interview by Urs Luthi)].

PMID- 22135995
TI  - [Prevention of delirium. Nursing interventions on multiple levels].

PMID- 22135994
TI  - [Information and communication technology. New ways to strengthen health
      competence].

PMID- 22135996
TI  - [Decubitus ulcer, accidental falls and malnutrition. Assessment data as the basis
      for better quallity].

PMID- 22135997
TI  - [Research in nursing practice. A backpack filled with skills].

PMID- 22135998
TI  - [Job market. Job seekers in nursing care?].

PMID- 22135999
TI  - [Osteoporosis. Good patient education can prevent fractures].

PMID- 22136000
TI  - [Mobbing. Mostly the victim leaves, not the perpetrator].

PMID- 22136001
TI  - [Sensitive care, beyond the labels].

PMID- 22136002
TI  - [The volunteering in the nursing care unit. A breath of fresh air much
      appreciated].

PMID- 22136003
TI  - [Stress and burnout in psychiatry. A threat to the therapeutic relationship].

PMID- 22136004
TI  - [Patient safety. Safer surgery in Switzerland].

PMID- 22136005
TI  - [Do you know the publications of the ASI? Reference documents to discover].

PMID- 22136006
TI  - [40 years service in nursing care. Homage to Liliane Bergier].

PMID- 22136008
TI  - [Culturally sensitive nursing care].

PMID- 22136007
TI  - [The soccer game. The patient as captain of the team].

PMID- 22136009
TI  - The epidemic of children's dental diseases: putting teeth into the law.

PMID- 22136010
TI  - No role for apology: remedial work and the problem of medical injury.

PMID- 22136011
TI  - Delayed and denied: toward an effective ERISA remedy for improper processing of
      healthcare claims.

PMID- 22136012
TI  - Transgender health at the crossroads: legal norms, insurance markets, and the
      threat of healthcare reform.

PMID- 22136013
TI  - [Indications and prospects of acupuncture-moxibustion].

PMID- 22136015
TI  - [Intervention of electroacupuncture for patients with impaired glucose
      tolerance].
AB  - OBJECTIVE: To explore the regulation on 2-hour postprandial blood glucose (2h
      PBG) for patients with impaired glucose tolerance (IGT) in the intervention with
      electroacupuncture. METHODS: Sixty cases of IGT were divided randomly into an
      electroacupuncture group and a blank control group, 30 cases in each one. In
      electroacupuncture group, electroacupuncture was applied to Shenshu (BL 23),
      Pishu (BL 20), Zusanli (ST 36) and Sanyinjiao (SP 6) in the intervention, lasting
      for 6 sessions. In blank control group, no any intervention was adopted. The
      levels of fasting blood-glucose (FBG), 2 h PBG with 75 g glucose and hemoglobin
      Alc (HbAlc) were observed before and after the intervention for the patients in
      electroacupuncture group, as well as in blank con trol group. RESULTS: The total
      effective rate was 76.7% (23/30) in electroacupuncture group, which was superior
      to that of 16.7% (5/30) in blank control group (P < 0.01). 2h PBG [(7.08 +/-
      0.74) mmol/L] and HbAlc [(5.74 +/- 0.35)%] were down-regulated significantly
      after the intervention with electroacupuncture of 6 sessions in
      electroacupuncture group. The therapeutic effects of it were superior remarkably
      to those [(8.93 +/- 1.87) mmol/L, (5.97 +/- 0.591)%] in blank control group,
      indicating statistical significant difference (P < 0.01, P < 0.05). But, there
      was no any impact for the patients with normal FBG. CONCLUSION:
      Electroacupuncture may be the means to achieve the clinical effective
      intervention for the people with IGT and the approach in the prevention and
      treatment of diabetes at the early stage.

PMID- 22136014
TI  - [Impact of acupoint heat-sensitive moxibustion on lung function and life quality
      of patients with chronic persistent bronchial asthma: a randomized controlled
      study].
AB  - OBJECTIVE: To observe the impact of heat-sensitive moxibustion on lung function
      in chronic persistent bronchial asthma and analyze its effect on the improvement
      of life quality as well as compare its efficacy with Seretide inhaler. METHODS:
      Fifty-seven cases were divided into a heat-sensitive moxibustion group (28 cases)
      and a Seretide group (29 cases) according to the random number table. In heat
      sensitive moxibustion group, the therapy of heat-sensitive moxibustion was
      applied to the regions at the level of Feishu (BL 13) and Geshu (BL 17), or to
      the heat-sensitized points in the region 6 cun lateral from the 1st and 2nd
      intercostal spaces in the chest. The treatment was given continuously for 8 days,
      once per day, 12 treatments should be ensured in the later 22 days of the 1st
      month. In the later two months since then, 15 treatments should be ensured each
      month (< or = 1 treatment each day). In Seretide group, Seritide manufactured in
      GlaxoSmithKLine was used, one inhalation each time, twice per day. The cases in
      both groups were received treatment for 3 months. The changes in lung function
      such as forced expiratory volume one second (FEV1), TCM symptoms score, Asthma
      Control Test (ACT) and St George's Respiratory Questionnaire (SGRQ) were assessed
      and compared between two groups and within group separately. RESULTS: Lung
      function as FEV1 was improved in either group (P < 0.05, P < 0.01). The terminal
      improvement effects on symptoms of Chinese medicine, life quality and others were
      same between two groups (all P > 0.05). But the improvements in general
      situation, chills, fever and sweating in heat-sensitive moxibustion group were
      superior to those in Seretide group (both P < 0.05). Concerning to the
      improvement in respiratory symptoms, the effect of Seretide was better than that
      of heat-sensitive moxibustion (P < 0.05). CONCLUSION: Heat-sensitive moxibustion
      improves lung function, relieves clinical symptoms and benefits life quality for
      patients with chronic persistent bronchial asthma. It's efficacy on the disease
      is equal to the internationally-recognized effect of Seretide.

PMID- 22136016
TI  - [Acupuncture-moxibustion at Baihui (GV 20) for 56 cases of vasovagal syncope].

PMID- 22136017
TI  - [Efficacy observation on the needling depth recorded in Lingshu (Miraculous
      Pivot) for irritable bowel syndrome of diarrhea].
AB  - OBJECTIVE: To observe the clinical efficacy of the needling depth recorded in
      Lingshu (Miraculous Pivot) for irritable bowel syndrome of diarrhea (IBS-D) in
      Germany. METHODS: With the needling technique recorded in Lingshu: Jingshui
      (Miraculous Pivot: Meridian Water), 21 cases of IBSD were treated with
      acupuncture at Zhangmen(lR 13), Zhongwan(CV 12), Tianshu (ST 25), Guanyuan(CV 4),
      Qimen (LR 14), Quchi (LI 11), Hegu (LI 4), Yinlingquan(SP 9), Zusanli (ST 36) and
      Taichong (LR 3), 0. 1-0. 6 cun (2-12 mm) in depth. Even needling technique was
      applied. The treatment was given 2-3 times each week, and 8 treatments made one
      session. The efficacy and the scale for the severity degree of symptom (IBS-SSS)
      were observed in 1-2 sessions of treatment. RESULTS: The total effective rate was
      52.4% (11/21) in the 1st session and was 90.5% (19/21) in the 2nd session. The
      efficacy in the 2nd session was superior to that in the 1st session (P < 0.05).
      IBS-SSS was 143.58 +/- 70.15 in the 1st session and was 115.98 +/- 72.68 in the
      2nd session, all reduced obviously as compared with those before treatment (all P
      < 0.01). The reducing degree in the 2nd session was much remarkable than that in
      the 1st session (P < 0.05). CONCLUSION: The better clinical efficacy has been
      achieved for IBS-D treated with needling depth recorded in Lingshu (Miraculous
      Pivot) in Germany. The longer session of treatment is, the better efficacy is
      obtained.

PMID- 22136018
TI  - [Discussion on clinical application of five-shu points about "nourishing the
      mother and deficient the son"].

PMID- 22136019
TI  - [Simple motor aphasia caused by cerebral infarction treated with blood-pricking
      at Yamen (GV 15) combined with language training].
AB  - OBJECTIVE: To explore an effective method for pure motor aphasia caused by
      cerebral infarction. Methods Ninety-six cases were randomized into a blood
      pricking therapy combined with rehabilitation group (comprehensive group), a
      blood-pricking therapy group and a rehabilitation group, 30 cases in each group.
      Based on the routine therapy of primary disease, blood-pricking at Yamen (GV 15)
      combined with language rehabilitation training was applied in comprehensive
      group, blood-pricking at Yamen (GV 15) was applied only in blood-pricking therapy
      group, and language rehabilitation training was applied in rehabilitation group.
      The classification table of speech ability in Speech Therapy and Chinese Standard
      Aphasia Test Battery by Beijing Medical University were adopted to evaluate the
      clinical effects of speaking functions and words information, fluency, retelling,
      and naming of aphasia. RESULTS: After 30 days treatment, the speaking functions
      of 3 groups were all significantly improved. The total effective rate was 90.6%
      (29/32) in comprehensive group, which was superior to that of 84.4% (27/32) in
      blood-pricking therapy group and 75.0% (24/32) in rehabilitation group (both P <
      0.01), and it in blood-pricking therapy group was superior to that in
      rehabilitation group (P < 0.05). The scores of words information and fluency in
      comprehensive group were much more higher than those in blood-pricking therapy
      group and rehabilitation group (both P < 0.01); retelling and naming in
      comprehensive group were higher than those in other two groups (both P < 0.05);
      the scores of words information and fluency in blood-pricking therapy group were
      higher than those in rehabilitation group (both P < 0.05). CONCLUSION: The
      curative effect of simple motor aphasia caused by cerebral infarction treated
      with blood-pricking at Yamen (GV 15) combined with language training was
      significantly, superior to that with either blood-pricking therapy or
      rehabilitation, especially in words information and fluency aspects.

PMID- 22136020
TI  - [Retrospective controlled study on early postoperative inflammatory small bowel
      obstruction treated with electroacupuncture and acupuncture].
AB  - OBJECTIVE: To reveal the efficacy on early postoperative inflammatory small bowel
      obstruction (EPISBO) treated with electroacupuncture and acupuncture separately
      and make the comparison of the efficacy difference. METHODS: Through
      retrospective analysis, 459 cases of EPISBO were divided into an
      electroacupuncture group (355 cases) and an acupuncture group (104 cases). Based
      on routine treatment, Zusanli (ST 36), Shangjuxu (ST 37), Taichong (LR 3),
      Gongsun (SP 4) and Xuanzhong (GB 39) were selected in either group, but
      stimulated with electroacupuncture and acupuncture separately, once per day, for
      30 min each time. RESULTS: All of 459 cases were cured. The average days of
      curative achievement in electroacupuncture group were less apparently than those
      in acupuncture group (13.5 +/- 7.5 vs. 20.8 +/- 6.5, P < 0.05). The days of
      curative achievement in either group were less significantly than those treated
      with parenteral nutrition and medication recorded in literatures (32.0 +/- 7.0,
      both P < 0.05). CONCLUSION: Either electroacupuncture or acupuncture achieves a
      significant efficacy on EPISBO, but the efficacy of electroacupuncture is better
      than that of acupuncture.

PMID- 22136021
TI  - [Observation on therapeutic effect of electroacupuncture at Jiaji (EX-B 2) and
      points of bladder meridian mainly for lumbar disc herniation].
AB  - OBJECTIVE: To compare the efficacy differences between electroacupuncture and
      medication in lumbar disc herniation. METHODS: Eighty-five cases of lumbar disc
      herniation were randomly divided into an electroacupuncture group (45 cases) and
      a medication group (40 cases). The electroacupuncture group was treated with
      electroacupuncture at Jiaji (EX-B 2), Shenshu (BL 23), Qihaishu (BL 24),
      Guanyuanshu (BL 26), Dachangshu (BL 25) and Yangtlingquan (GB 34) etc., once a
      day; and the medication group was treated with oral administration of Fugui
      Gutong capsule (3 times a day, 4 capsule each time) and 0.3 g ibuprofen (once a
      day). The scores of clincial symptoms and therapeutic effect were observed before
      and after treatment. Results In the electroacupuncture group, the effective rate
      was 84.4% (38/45), which was superior to that of 65.0% (26/40) in the medication
      group (P < 0.05). After treatment, the scores of symptoms significantly decreased
      in the two groups (both P < 0.01), and the reduction of scores in
      electroacupuncture group was superior to that in medication group (P < 0.05, P <
      0.01). CONCLUSION: Electroacupuncture at Jiaji (EX-B 2) and points of Bladder
      Meridian mainly has a better therapeutic effect on lumbar disc herniation, which
      is superior to oral administration of fugui gutong capsule and ibuprofen.

PMID- 22136022
TI  - [Acute ankle sprain treated with daling (PC 7) penetrating to yuji (LU 10) as
      main].

PMID- 22136023
TI  - [Forty-eight cases of intractable urticaria treated with moxibustion at belt
      vessel].

PMID- 22136024
TI  - [Effects of retained needling and non-retained needling on regulation of the
      cardiac autonomic nerve].
AB  - OBJECTIVE: To investigate the mechanism of retained needling and non-retained
      needling on the physiologic regulating effect of the cardiac autonomic nerve in
      healthy persons. METHODS: Sixty volunteers were randomly divided into a retained
      needling group and a non-retained needling group, 30 cases in each group. They
      were all received perpendicular needling at Neiguan (PC 6) and Jianshi (PC 5)
      retaining for 20 min in the retained nee dling group and without retaining in the
      non-retained needling group. The heart rate variability (HRV) indices, i.e., R-R
      interval, low frequency (LF), high frequency (HF) and LF/HF were observed.
      RESULTS: Compared with before acupuncture, the R-R interval were significant
      increased during the stimulation period and during the post-stimulation period in
      the retained needling group, especially during the stimulation period (all P <
      0.01), and during the post-stimulation period of 5 min and 10 min in the non
      retained needling group (P < 0.01, P < 0.05), then returned to pre-acupuncture
      level quickly, and the R-R interval in the retained needling group was
      significant ly higher than that in the non retained needling group at 10 min (P <
      0.05). At 5 min, the HF were significantly higher, and the LF/HF were
      significantly lower than those before acupuncture (P < 0.01, P < 0.05), and there
      was no obvious change in LF in both groups. CONCLUSION: Retained needling and non
      retained needling at Neiguan (PC 6) and Jianshi (PC 5) can both excite cardiac
      vagus nerve briefly and then the acupuncture effects reduce grad ually until
      disappearance, while no obvious changes can be found with cardiac sympathetic
      activity. Both of needling can reduce heart rate and the action time of heart
      rate decrease by retained needling is longer than non-retained needling.

PMID- 22136025
TI  - [Case of bulbar conjunctiva-lymphatics blokage in the left eye].

PMID- 22136026
TI  - [Comparative study on curative effects of stroke treated with acupuncture by
      NIRS].
AB  - OBJECTIVE: To compare the intracephalic imaging differences of stroke treated
      with combined therapy of scalp and body acupuncture and body acupuncture only, in
      order to apply the image basis for the differences of clinical curative effects.
      METHODS: Twenty cases of stroke were randomized into a body acupuncture group
      (group A) and a scalp and body acupuncture group (group B), ten cases in each
      group respectively. In group A, body acupuncture was applied simply, and
      different acupoints were selected according to the symptoms: Shousanli (LI 10),
      Jianliao (TE 14), Huantiao (GB 30) and Jiaji (EX-B 2) etc. were selected for
      hemiplegia, Fengchi (GB 20), Xiaguan (ST 7) and Quanliao (SI 18) etc. were for
      facial paralysis, Fengfu (GV 16) and Lianquan (CV 23) etc. were for aphasia. In
      group B, combined therapy were applied, the body acupoints selection was same as
      above; for scalp acupoints, corresponding motor area, sensory area and foot motor
      sensory area were selected. Instant changes of local cerebral blood flow before
      and after treatment were examined and evaluated by NIRS and the curative effects
      of both groups were evaluated. RESULTS: The total therapeutic effective rate was
      90.0% (9/10) and the basically cured rate was 30.0% (3/10) in group A; and 100.0%
      (10/10) and 50.0% (5/10) respectively in group B, indicating that the clinical
      curative effect in group B was superior to that in group A at 20, 30 min of
      acupuncture treatment (P < 0.05). Both imaging results showed that blood flows of
      prefrontal cortex in both groups were increased with varying degrees after
      treatment (P < 0.05, P < 0.01); the cerebral blood flow in group B was much more
      improved than that in group A at 20, 30 min of acupuncture treatment (all P <
      0.05). CONCLUSION: Acupuncture can significantly increase blood flow and oxygen
      saturation in brain cortex, and the effect with combined therapy of scalp and
      body acupuncture is superior to that with body acupuncture.

PMID- 22136027
TI  - [Application of "regulating spirit and conducting qi" therapy in treatment of
      psychological diseases].
AB  - Taking the clinical curative effects of psychological diseases treated with
      "regulating spirit and conducting qi" therapy as the starting point, the
      manipulation and technology method of "regulating spirit and conducting qi"
      therapy are introduced in the paper. Based on analysis of "conducting qi" therapy
      of Neijing (Internal Classic), it is summarized that, in "regulating spirit and
      conducting qi" therapy, tardiness and tenderness are taken as technical core of
      manipulation, individualization of patients is taken as basis, and regulation on
      spirit as key issue of technology, so as to rapidly, effectively and safely
      regulate the functional status of emotion and organism. It is aq effective
      technology method for treating psychological diseases, especially for insomnia,
      anxiety and somatic symptoms, with better curative effects.

PMID- 22136028
TI  - [Electroacupuncture at back-shu points as main combined with solar-term
      moxibustion for 150 cases of bronchial asthma].

PMID- 22136029
TI  - [Correlation study on effects of electroacupuncture on the muscle condition and
      MNCV in rabbits with lumbar nerve root compression].
AB  - OBJECTIVE: To observe the effects of electroacupuncture on the muscle condition
      and electrophysiology of the muscle in rabbits with lumbar nerve root compression
      and to explore potential mechanisms. METHODS: Twenty-four New Zealand white
      rabbits were randomly divided into a normal group, a model group, a medication
      group and an electroacupuncture group. The rabbit model with lumbar nerve root
      compression was established in the model group, the medication group and the
      electroacupuncture group. The model and the treatment were not produced in the
      normal group. The medication group was treated with oral administration of
      Loxoprofen tablets at a dose of 30 mg each day for 14 days. The
      electroacupuncture group was treated with electroacupuncture at "Jiaji" (EX-B 2)
      of L5 and L6 for 14 days. The hibateral muscle condition before and after making
      model and after treatment was detected and the electromyogram and the nerve
      conduction velocity (NCV) were observed. RESULTS: The spontaneous potential and
      the insertion potential were increased in the model group, the medication group
      and the electroacupuncture group after making model. The value of the activation
      and the relaxed condition of the strength-creep (ARCSC) in the right muscle was
      significantly decreased. The motor nerve conduction velocity (MNCV) and the wave
      amplitude of evoked potential (WAEP) were significantly decreased in the model
      group, the medication group and the electroacupuncture group after treatment, but
      the value of MNCV and WAEP in the electroacupuncture group, and ARCSC in the
      right muscle in the electroacupuncture group and the medicine group were closed
      to those level in the normal group, among them, the relaxed condition in the
      electroacupuncture group was more close to the level in the normal group.
      CONCLUSION: Electroacupuncture can improve the strength-creep condition of the
      muscle that damage nerve place controls and the electrophysiology of the muscle
      can recover the MNCV and the wave amplitude of evoked potential in the
      compression nerve root.

PMID- 22136030
TI  - [Effects of electroacupuncture on expression of calmodulin in the hippocampus of
      rats with cerebral ischemia-reperfusion injury].
AB  - OBJECTIVE: To investigate the protective effect of electroacupuncture (EA) on
      injured neurons and the signal transduction mechanism of calmodulin (CaM) in rats
      with cerebral ischemia-reperfusion injury (CIRI). METHODS: A total of 25 SD rats
      were randomly divided into a sham-operation group, a model group, an EA. group, a
      TFP group and an EA+TFP group. The rat model of middle cerebral artery occlusion
      (MCAO) was established by the modified Longa thread occlusion method. The EA
      group was treated with EA at "Dazhui" (GV 14) and "Baihui" (GV 20) for 30
      minutes. The TFP group was treated with lumbar intrathecal injection of
      Trinuoperazine (TFP) at a dose of 40 microL/kg, the inhibitor of CaM. The EA +
      TFP group was treated with EA combined with TFP, and the sham-operation group and
      the model group without any treatment. The neurology deficit score was evaluated
      by the Julio's neuroethology score methods in all rats, and the expression of CaM
      in cerebral hippocampus tissue was detected with immunohistochemical method in
      different intervention condition. RESULTS: (1) In comparison with the model group
      of 6.90 +/- 1.66, the neuroethology score in the EA group of 14.50 +/- 1.08, the
      TFP group of 11.70 +/- 1.06 and the EA + TFP group of 14.30 +/- 1.06 were all
      significantly increased (all P < 0.01), while those still were all lower than the
      sham group of 17.60 +/- 0.52 (all P < 0.01), and the EA group was better than the
      TFP group (P < 0.01). (2) In comparison with the sham group of 0.080 +/- 0.045,
      the immune positive expression score of CaM protein in hippocampus in the model
      group of 1.680 +/- 0.268 was sig nificantly increased (P < 0.01). In comparison
      with the model group, the expression score of CaM protein in the EA group of
      0.880 +/- 0.179, the TFP group of 0.720 +/- 0.179 and the EA + TFP group of 0.420
      +/- 0.249 were all significantly reduced (all P < 0.01), and the expression score
      of CaM in the EA + TFP group was lower than that in the TFP group (P < 0.05).
      CONCLUSION: EA can reduce the injury of cerebral neurons induced by CIRI in rats
      and promote the recovery, which may be related to its effect in regulating CaM
      signaling pathway after the ischemia-reperfusion injury.

PMID- 22136031
TI  - [Protecting action of acupuncture-drug compound anesthesia with different
      frequency electroacupuncture on stress reaction in pneumonectomy].
AB  - OBJECTIVE: To observe the protective effect of acupuncture-drug compound
      anesthesia with different frequency electroacupuncture on stress reaction in
      pneumonectomy and to explore potential mechanisms. METHODS: Eighty patients
      scheduled for pneumonectomy were randomly divided into four groups, named group
      A, B, C and D, 20 cases in each group. General anesthesia and single lung
      protective mechanical ventilation were produced in all the groups. They were
      treated with acupuncture at Houxi (SI 3), Zhigou (TE 6), Neiguan (PC 6), and Hegu
      (Li 4) 30 min before general anesthesia, and then with Han's acupoint nerve
      stimulator (HANS-200). The acupuncture needles without needle bodies were pasted
      on the acupoints and the electroacupuncture were not turned on in group A, and
      the 2 Hz continuous wave were produced in group B, and 100 Hz continuous wave
      were produced in group C and the 2 Hz/100 Hz were produced in group D. The
      supplementary anesthesia medicine during pneumonectomy, heart rate (HR), mean
      arterial pressure (MAP), CD4+ /CD/ in venous blood before and after the surgery,
      and the contents of epinephrine (E) and cortisol (Cor) in plasma at the time of
      inter-room and outer-room were detected. RESULTS: (1) The supplementary fentanyl
      in group B and C were lower than those in group A and D (P < 0.05, P < 0.01). (2)
      The MAP in the four groups at intratracheal intubation (T1) were all higher than
      those at before anesthesia (T0) (all P < 0.01), and the ascending extent in group
      B, C and D were lower than that in group A (all P < 0.01). The HR at T in group A
      was higher than that at T0 (P < 0.05) and there were no significant differences
      in the other groups (all P > 0.05), and the ascending extent in group B and D
      were lower than that in group A (both P < 0.05). The MAP and HR at the other
      moment in all the groups were maintained stable. (3) CD4+ /CD8+ in group A after
      pneumonectomy was lower than that before the surgery (P < 0.05), and there were
      no significant differences in the other groups (all P > 0.05). (4) The content of
      E and Cor after the surgery were all increased (all P < 0.01), and the ascending
      extent of E in group D was lower than that in group A (P < 0.05), and the
      ascending level of Cor in group B and D were lower than that in group A (P <
      0.01) and group B compared with group C and D were got the same result.
      CONCLUSION: Acupuncture-drug compound anesthesia can attenuate the stress
      reaction so as to protect organs under the condition of less drug and can
      alleviates the undulate phenomenon of MAP and HR at intubation and stabilize CD4+
      /CD8+ after pneumonectomy. Among them, the 2 Hz and 2 Hz/100 Hz
      electroacupuncture groups have the comparatively better effects.

PMID- 22136032
TI  - [Surrounded needling at great trochanter mainly for 42 cases of chronic bursitis
      of hip joint].

PMID- 22136033
TI  - [Case of phantom limb pain].

PMID- 22136034
TI  - [Academic thinking on Cheng Dan-an's theory of acupuncture].
AB  - Academic thinking on Cheng Dan-an's theory of acupuncture is analyzed. It is
      stated that Cheng's theory of acupuncture has put exceptional emphasis and
      efforts on inheriting the tradition and learning from the west by pursuing truth.
      He concisely reinterpretes the traditional theory of acupuncture and practically
      improves the acupuncture instruments according to clinical experiences.
      Meanwhile, he introduces the advanced achievements of anatomy and neurophysiology
      into acupuncture teaching and research, which plays an important role for
      modernization of acupuncture.

PMID- 22136035
TI  - [Mechanism and case study on treatment of refractory diseases of oculopathy with
      abdominal eight-diagram holotherapy].
AB  - Mechanism and case study on treatment of refractory diseases of oculopathy with
      Dr. Shen Feng-ren's abdominal eight-diagram holotherapy are introduced in the
      article. The accurate location of acupoints, comprehensive understanding of the
      theory and features of the eight-diagram are held as the prerequisites of the
      application of the therapy. The combination of the theories of five wheels, five
      zang organs, and mother and son relation among the five elements are taken as the
      theoretical foundation of the treatment. And clinical analyses on three cases
      treated with the theory are provided as well.

PMID- 22136037
TI  - [Development and significance of theory on yang meridians].
AB  - The theory on yang meridians was reviewed from the aspect of intellectual
      history. It is held that the significant change of the relation between yang
      meridians and zang-fu organs influenced the theory and the sense of yang
      meridians. The comprehension on yang meridians closely related with the
      understanding on the whole classic theory of meridian. And the knowledge on
      features of meridians would finally affect the proper understanding of
      differentiation of syndromes according to meridians and collaterals. From the
      view of point, new comprehensions are proposed including the interior and
      exterior relations of meridians, relations between meridians and zang-fu organs,
      specialty of differentiation of syndromes according to meridians and collaterals,
      syndromes of yang meridians and changing of the indications of acupoints.

PMID- 22136036
TI  - [Thirty-two cases of scapulohumeral periarthritis treated with superficial
      puncture combined with elongated needle therapy].

PMID- 22136038
TI  - [Plum blossom needling for 74 cases of scapulohumeral periarthritis].

PMID- 22136039
TI  - [Influence factors on supply and demand changes in the field of acupuncture and
      moxibustion].
AB  - Based on principles of health economy and the present situation, the possibility
      and regularity on changes in the supply and demand field of acupuncture and
      moxibustion through various viewpoints were analyzed, which included demand and
      supply elasticity of acup-mox services to market price and the relevant factors,
      categories and nature of acup-mox services, business idea of supplier on the
      strength of marginal cost and marginal benefit, expenditure level and inclination
      of demander, complementary and substitutive treatment of acup-mox therapy, and
      the relevant time and geographic factors to change in quantity demand and supply.
      Therefore, it could be applied as reference to redaction and reform of the
      relevant health economics policy by health administrative management.

PMID- 22136040
TI  - [Rethink on "experiment of progated sensation along meridians"].
AB  - The theory, methods and ideas of "experiment of progated sensation along
      meridians (PSM)" were examined in the article through retrieval of ancient
      medical books, excavating the theory of meridians, the qi of meridians, ying
      (nutrient) qi, wei (defensive) qi and the related acupuncture techniques. The
      result shows that PSM is not the reaction of the meridian qi, but the reflection
      of wei (defensive) qi. Therefore, whether the experiment of PSM revealed with the
      phenomenon of meridian and all hypothesis based on it or not are still remained
      as a question. However, although PSM is considered to be related with the wei
      (defensive) qi, it can not be concluded that the experiment of PSM revealed the
      function of the wei (defensive) qi.

PMID- 22136041
TI  - [Discussion on research status of acupoints-acupuncture effect].
AB  - To analyze the status of attention on specificity of acupuncture in the study of
      mechanism of acupuncture-acupuncture effect. By dissecting the relationship
      between acupoints stimulatory method and acupoints attribute, the research
      approaches to the acupoint stimulatory effect based on "meridian awakening
      threshold" are put forward so as to explore the research strategy of acupuncture
      mechanism.

PMID- 22136042
TI  - [Fifty-five cases of postoperative intestinal obstruction treated by quick
      cupping therapy and acupuncture].

PMID- 22136043
TI  - [Study progression on the specificity of meridian points effectiveness].
AB  - The present situation of the study on the specificity of meridian points
      effectiveness through checking up the relevant literatures on the study of this
      subject published in recent 10 years from the databases such as CNKI and SCI are
      summarized in the paper. It is indicated in the summarization that the
      effectiveness of meridian points is specific and the meridian points bring their
      role into play probably through the biological mechanism in the body. But, it is
      still limitative in systematic, complete and scientific study on such conclusion.
      In future, the relevant study is required by adopting adequately modern
      scientific technology and facility, strict and scientific experiment designs as
      well as assessment method and taking extensive diseases or disease models as the
      carriers.

PMID- 22136044
TI  - [Two hundreds and thirty-eight cases of kidney-yang deficiency syndrome treated
      with fine fire needle].

PMID- 22136046
TI  - Microfluidic paper-based analytical devices: from POCKET to paper-based ELISA.

PMID- 22136045
TI  - Uptake of methacrolein into aqueous solutions of sulfuric acid and hydrogen
      peroxide.
AB  - Multiphase acid-catalyzed oxidation by hydrogen peroxide has been suggested to be
      a potential route to secondary organic aerosol (SOA) formation from isoprene and
      its gas-phase oxidation products, but the kinetics and chemical mechanism remain
      largely uncertain. Here we report the first measurement of uptake of methacrolein
      into aqueous solutions of sulfuric acid and hydrogen peroxide in the temperature
      range of 253-293 K. The steady-state uptake coefficients were acquired and
      increased quickly with increasing sulfuric acid concentration and decreasing
      temperature. Propyne, acetone, and 2,3-dihydroxymethacrylic acid were suggested
      as the products. The chemical mechanism is proposed to be the oxidation of
      carbonyl group and C?C double bonds by peroxide hydrogen in acidic environment,
      which could explain the large content of polyhydroxyl compounds in atmospheric
      fine particles. These results indicate that multiphase acid-catalyzed oxidation
      of methacrolein by hydrogen peroxide can contribute to SOA mass in the
      atmosphere, especially in the upper troposphere.

PMID- 22136047
TI  - 8th Exploratory Measurement Science Group Ardgour Symposium.
AB  - Once again the impressive 18th Century Ardgour House, located in the stunning
      highland scenery of Fort William, Scotland, hosted the annual Exploratory
      Measurement Science Group Ardgour Symposium. The 5 day meeting, now in its 8th
      year, is organized to bring together a diverse international group of young and
      established scientists, who are interested in the development, or application, of
      advanced analytical instrumentation. This year's meeting contained presentations
      from world-leading academics, instrument manufacturers and pharmaceutical
      researchers, fostering wide-ranging interdisciplinary discussion.

PMID- 22136048
TI  - Incurred sample reanalysis: a global transformation.
AB  - Incurred sample reanalysis (ISR) is accepted as both a fundamental concept and an
      integral part in the conduct of pharmacokinetic, bioequivalence and preclinical
      safety studies. Reproducibility demonstrated by ISR reinforces confidence that
      the method is valid and the results dependable. In this article, the history of
      the uptake of ISR is discussed and the current practices described. The industry
      is given credit for its awareness of the importance of, and implementation of,
      ISR practices in bioanalytical laboratories. Finally, in the context of the
      recent publication of guidelines for ISR by the EMA, implications for
      globalization and harmonization of regulations pertaining to ISR are described.

PMID- 22136049
TI  - Hydrophilic interaction LC-MS/MS analysis of opioids in urine: significance of
      glucuronide metabolites.
AB  - BACKGROUND: In clinical laboratories, a large proportion of the toxicology
      workload is drug confirmations. Our GC-MS method for opioid confirmation detects
      total codeine, morphine, hydrocodone, hydromorphone, oxycodone and oxymorphone.
      The objective of this study was to develop a LC-MS/MS assay measuring the above
      drugs and glucuronide metabolites. In addition, to determine if measuring free
      drug only would lead to false negative results. RESULTS: In 85 patient urines,
      43% were positive for morphine glucuronide, but not morphine, 48% were positive
      for hydromorphone glucuronide, but not hydromorphone, 33% were positive for
      codeine glucuronide, but not codeine, and 44% were positive for oxymorphone
      glucuronide, but not oxymorphone. CONCLUSION: We developed an LC-MS/MS assay
      capable of detecting codeine, morphine, hydrocodone, hydromorphone, oxycodone,
      oxymorphone and glucuronide metabolites. Detection of free drug only led to false
      negative confirmations.

PMID- 22136050
TI  - High-throughput polymer monolith in-tip SPME fiber preparation and application in
      drug analysis.
AB  - BACKGROUND: A simple, low-cost and reproducible automated procedure has been
      developed to prepare in-tip solid-phase microextraction (SPME) fibers coated with
      polymer monoliths using a photopolymerization technique. Up to 96 fibers were
      prepared at one time using a polymerization mixture consisting of ethylene glycol
      dimethacrylate, dimethoxy-alpha-phenylacetophenone and 1-decanol. RESULTS: The
      optimization procedures that affected polymer morphology, such as compositions of
      the crosslinkers and porogens, polymerization time and fiber thickness as well as
      extraction efficiency of the immobilized Oasis hydrophilic-lipophilic-balanced
      extraction sorbent were investigated. Also, the reproducibility of automated in
      tip SPME fiber preparation, as well as sample process parameters, such as sample
      extraction and desorption volumes, are discussed. CONCLUSION: The performance of
      the polymer monoliths in-tip SPME assessed with a model drug compound from
      clinical studies and a head-to-head comparison using in-tip SPME and conventional
      SPE clearly demonstrated that the SPME is a feasible approach for routine drug
      analysis in the pharmaceutical industry.

PMID- 22136051
TI  - Proposal for a new protein therapeutic immunogenicity titer assay cutpoint.
AB  - BACKGROUND: Generally, immunogenicity assessment strategies follow this assay
      triage schema: screen->confirm->titer. Each requires the determination of a
      threshold value (cutpoint) for decision making. No guidance documents exist for
      the determination of a specific titration assay cutpoint. The default practice is
      to use the screening assay cutpoint, frequently leading to controls or samples
      not reaching this cutpoint. We propose a method for determination of a titration
      cutpoint based upon the variance of the negative-control sample. RESULTS:
      Positive-control samples that did not cross a screening cutpoint did cross the
      titer cutpoint, albeit generating slightly lower titer values. CONCLUSION: Our
      approach is consistent with the statistical methods currently recommended for the
      screening and confirmatory assay cutpoints and is operationally simple and
      efficient.

PMID- 22136052
TI  - Bioanalytical aspects of clinical mass balance studies in oncology.
AB  - Clinical mass balance studies aim to investigate the absorption, distribution,
      metabolism and excretion (ADME) of a(n) (often radiolabeled) drug, following a
      single administration to humans. They are perfectly suited to determine the
      disposition and major metabolic pathways of a drug, the exposure to the parent
      drug and its metabolites, and the rate and route of elimination. A mass balance
      study, however, poses interesting challenges to the analysis of parent drug and
      metabolites in different biological matrices. Using recent clinical mass balance
      studies in oncology as an example, this review focuses on the aspects of mass
      balance studies, from bioanalytical assay development, analysis of clinical
      samples to reporting of study results. Along the way, it discusses bioanalytical
      problems and practical solutions.

PMID- 22136053
TI  - In vitro cytokine release assays: reducing the risk of adverse events in man.
AB  - The induction of cytokine release is a common consequence of the administration
      of therapeutic antibodies and in most cases is either tolerated by the patient or
      can be managed clinically by the administration of corticosteroids. However, in
      2006, the administration of TGN1412 to six patients in a Phase I trial resulted
      in a unprecedentedly high level of cytokine release, systemic organ failure and
      the hospitalization of the subjects. Whilst the path to failure in this incident
      was multifactorial, at least one contributing factor was the lack of a robust in
      vitro model that would allow the prediction of the in vivo activity of a
      therapeutic antibody. In this article we review the current 'state of the art' of
      in vitro cytokine release assays and explore potential future developments.

PMID- 22136054
TI  - State-of-the-art MS technology applications in lung disease.
AB  - Two frontline MS technologies, which have recently gained much attention, are
      discussed within the scope of this review. Besides a brief summary on the
      contemporary state of lung cancer and chronic obstructive pulmonary disease, the
      principles of multiple reaction monitoring and matrix assisted laser desorption
      ionization (MALDI) MS imaging are presented. A comprehensive overview of
      quantitative mass spectrometry applications is provided, covering multiple
      reaction monitoring assay developments for analysis of proteins (biomarkers) and
      low-molecular-weight compounds (drugs) with a special focus on the disease areas
      of lung cancer and chronic obstructive pulmonary disease. The MALDI-MS imaging
      applications are discussed similarly, providing references to studies conducted
      on lung tissues in order to localize drug compounds and protein biomarkers.

PMID- 22136056
TI  - There goes the neighbourhood: contextual control over the breadth of lexical
      activation when reading aloud.
AB  - There are currently two computational accounts of how the time to read
      pseudohomophones (like BRANE) and their nonword controls (like FRANE) varies with
      changes in context. In Reynolds and Besner's (2005) account, readers vary the
      breadth of lexical activation in response to changes in context. A competing
      account proposed by Kwantes and Marmurek (2007) and independently by Perry,
      Ziegler, and Zorzi (2007) has readers varying their response criterion in
      response to changes in context. The present work adjudicates between these two
      accounts by examining how the effect of neighbourhood density changes as a
      function of list context when reading pseudohomophones aloud. The results of an
      experiment and simulations from a leading computational model support the lexical
      breadth account, but are inconsistent with the response criterion account.

PMID- 22136060
TI  - Estimates of induced abortion in South Korea: health facilities survey.
AB  - AIM: The aim of this study was to estimate the national rates of induced abortion
      in South Korea, where no quantitative national studies of abortion exist because
      the procedure is illegal. MATERIALS AND METHODS: A survey of 25 hospitals and 176
      private clinics that provide induced abortions was conducted in 2005. The data
      were analyzed to estimate the nationwide rate of induced abortion. Indirect
      estimation methodology was used to calculate the number of annual induced
      abortions. RESULTS: In 2005, an estimated 342 433 induced abortions were
      performed in South Korea at a rate of 29.8 per 1000 women aged 15-44years. We
      observed that the abortion rate was higher in single women (31.6 per 1000 women)
      than in married women (28.6 per 1000 women). CONCLUSIONS: A significant number of
      induced abortions occur in both cohorts of married and unmarried women. To
      prevent serious physical harm to patients, the government should reconsider the
      practicality of the current statutes that prohibit women from seeking abortions
      from a qualified provider.

PMID- 22136061
TI  - Molecular mechanism of the effects of salt and pH on the affinity between protein
      A and human immunoglobulin G1 revealed by molecular simulations.
AB  - Protein A from the bacterium Staphylococcus aureus (SpA) has been widely used as
      an affinity ligand for purification of immunoglobulin G (IgG). The affinity
      between SpA and IgG is affected differently by salt and pH, but their molecular
      mechanisms still remain unclear. In this work, molecular dynamics simulations and
      molecular mechanics Poisson-Boltzmann surface area analysis were performed to
      investigate the salt (NaCl) and pH effects on the affinity between SpA and human
      IgG1 (hIgG1). It is found that salt and pH affect the interactions of the hot
      spots of SpA by different mechanisms. In the salt solution, the compensations
      between helices I and II of SpA as well as between the nonpolar and electrostatic
      energies make the binding free energy independent of salt concentration. At pH
      3.0, the unfavorable electrostatic interactions increase greatly and become the
      driving force for dissociation of the SpA-hIgG1 complex. They mainly come from
      the strong electrostatic repulsions between positively charged residues (H137,
      R146, and K154) of SpA and the positively charged residues of hIgG1. It is
      considered to be the molecular basis for hIgG1 elution from SpA-based affinity
      adsorbents at pH 3.0. The dissociation mechanism is then used to refine the
      binding model of SpA to hIgG1. The model is expected to help design high-affinity
      peptide ligands of IgG.

PMID- 22136062
TI  - Removal of organics and degradation products from industrial wastewater by a
      membrane bioreactor integrated with ozone or UV/H2O2 treatment.
AB  - The treatment of a pharmaceutical wastewater resulting from the production of an
      antibacterial drug (nalidixic acid) was investigated employing a membrane
      bioreactor (MBR) integrated with either ozonation or UV/H(2)O(2) process. This
      was achieved by placing chemical oxidation in the recirculation stream of the
      MBR. A conventional configuration with chemical oxidation as polishing for the
      MBR effluent was also tested as a reference. The synergistic effect of MBR when
      integrated with chemical oxidation was assessed by monitoring (i) the main
      wastewater characteristics, (ii) the concentration of nalidixic acid, (iii) the
      48 organics identified in the raw wastewater and (iv) the 55 degradation products
      identified during wastewater treatment. Results showed that MBR integration with
      ozonation or UV/H(2)O(2) did not cause relevant drawbacks to both biological and
      filtration processes, with COD removal rates in the range 85-95%. Nalidixic acid
      passed undegraded through the MBR and was completely removed in the chemical
      oxidation step. Although the polishing configuration appeared to give better
      performances than the integrated system in removing 15 out of 48 secondary
      organics while similar removals were obtained for 19 other compounds. The benefit
      of the integrated system was however evident for the removal of the degradation
      products. Indeed, the integrated system allowed higher removals for 34 out of 55
      degradation products while for only 4 compounds the polishing configuration gave
      better performance. Overall, results showed the effectiveness of the integrated
      treatment with both ozone and UV/H(2)O(2).

PMID- 22136063
TI  - Therapies using anti-angiogenic peptide mimetics of thrombospondin-1.
AB  - INTRODUCTION: The role of hrombospondin-1 (TSP1) as a major endogenous
      angiogenesis inhibitor has been confirmed by numerous studies and subsequent
      mechanistic discoveries. It has yielded a new class of potential drugs against
      cancer and other angiogenesis-driven diseases. AREAS COVERED: An overview of TSP1
      functions and molecular mechanisms, including regulation and signaling. Functions
      in endothelial and non-endothelial cells, with emphasis on the role of TSP1 in
      the regulation of angiogenesis and inflammation. The utility of duplicating these
      activities for drug discovery. Past and current literature on endogenous TSP1 and
      its role in the progression of cancer and non-cancerous pathological conditions
      is summarized, as well as the research undertaken to identify and optimize short
      bioactive peptides derived from the two TSP1 anti-angiogenic domains, which bind
      CD47 and CD36 cell surface receptors. Lastly, there is an overview of the
      efficacy of some of these peptides in pre-clinical and clinical models of
      angiogenesis-dependent disease. EXPERT OPINION: It is concluded that TSP1-derived
      peptides and peptide mimetics hold great promise as future agents for the
      treatment of cancer and other diseases driven by excessive angiogenesis. They may
      fulfill unmet medical needs including neovascular ocular disease and the diseases
      of the female reproductive tract including ovarian cancer.

PMID- 22136064
TI  - Quantitation of the hydroxycinnamic acid derivatives and the glycosides of
      flavonols and flavones by UV absorbance after identification by LC-MS.
AB  - A general approach was developed to quantify hydroxycinnamic acid derivatives and
      the glycosides of flavonols and flavones using UV molar relative response factors
      (MRRFs). More than 90 standards were analyzed by LC-MS and divided into five
      groups based on the lambda(max) of their band I absorbance profiles. For each
      group, a commercially available standard was chosen as the group reference
      standard. Response factors were determined for each standard in each group as
      purchased (MRRF) and, when possible, after vacuum drying (MRRF(D)). The MRRF(D)
      values for 17 compounds whose lambda(max) values fell within +/-2 nm of the group
      reference standard were 1.01 +/- 0.03. MRRF values for compounds whose
      lambda(max) values fell within +/-10 nm of the group reference standard were 0.96
      +/- 0.13. Group reference standards were used to quantify 44 compounds in Chinese
      lettuce, red onion, and white tea. This approach allows quantitation of numerous
      compounds for which there are no standards.

PMID- 22136065
TI  - A fiber chimeric CRAd vector Ad5/11-D24 double-armed with TRAIL and arresten for
      enhanced glioblastoma therapy.
AB  - Malignant gliomas remain refractory to treatment despite advances in chemotherapy
      and surgical techniques. Conditionally replicating adenoviral vector (CRAd) could
      kill the tumor cells by selectively replicating in neoplastic cells, which
      represents a novel strategy for tumor therapy. Although CRAd with a 24-bp
      deletion in CR2 of the E1 region (CRAd5-D24) has been shown to have a better
      therapeutic effect over the other types of CRAd vectors, the current CRAd5-D24
      still has some shortcomings for an efficient therapy of gliomas. In this study,
      we developed for the first time a novel vector CRAd5/11-D24.TRAIL/arresten by the
      following strategies: (1) modify CRAd5-D24 with Ad5/11 chimeric fiber to improve
      its infection efficiency for glioblastoma; and (2) insert two transgene
      expression cassettes into the E3 region and the region between the fiber and E4,
      respectively, for an enhanced therapeutic effect. The results indicated that the
      CRAd5/11-D24.TRAIL/arresten achieved nearly complete inhibition of glioma growth
      in nude mice possibly by increased antiangiogenesis and enhanced tumor apoptosis.
      The vector is the first reported E1A D24-deleted, Ad5/11 chimeric, and dual-armed
      oncolytic virus that shows markedly improved antitumor activities compared with
      the conventional oncolytic viruses. This novel antitumor agent should be
      evaluated further in future preclinical and clinical studies.

PMID- 22136066
TI  - Analysis of the role of Ser1/Ser2/Thr9 phosphorylation on myosin II assembly and
      function in live cells.
AB  - BACKGROUND: Phosphorylation of non-muscle myosin II regulatory light chain (RLC)
      at Thr18/Ser19 is well established as a key regulatory event that controls myosin
      II assembly and activation, both in vitro and in living cells. RLC can also be
      phosphorylated at Ser1/Ser2/Thr9 by protein kinase C (PKC). Biophysical studies
      show that phosphorylation at these sites leads to an increase in the Km of myosin
      light chain kinase (MLCK) for RLC, thereby indirectly inhibiting myosin II
      activity. Despite unequivocal evidence that PKC phosphorylation at Ser1/Ser2/Thr9
      can regulate myosin II function in vitro, there is little evidence that this
      mechanism regulates myosin II function in live cells. RESULTS: The purpose of
      these studies was to investigate the role of Ser1/Ser2/Thr9 phosphorylation in
      live cells. To do this we utilized phospho-specific antibodies and created GFP
      tagged RLC reporters with phosphomimetic aspartic acid substitutions or
      unphosphorylatable alanine substitutions at the putative inhibitory sites or the
      previously characterized activation sites. Cell lines stably expressing the RLC
      GFP constructs were assayed for myosin recruitment during cell division, the
      ability to complete cell division, and myosin assembly levels under resting or
      spreading conditions. Our data shows that manipulation of the activation sites
      (Thr18/Ser19) significantly alters myosin II function in a number of these assays
      while manipulation of the putative inhibitory sites (Ser1/Ser2/Thr9) does not.
      CONCLUSIONS: These studies suggest that inhibitory phosphorylation of RLC is not
      a substantial regulatory mechanism, although we cannot rule out its role in other
      cellular processes or perhaps other types of cells or tissues in vivo.

PMID- 22136067
TI  - Identification and characterization of three cholinesterases from the common bed
      bug, Cimex lectularius.
AB  - We identified and characterized the full-length cDNA sequences encoding two
      acetylcholinesterases (ClAChE1 and ClAChE2) and a salivary gland-specific
      cholinesterase-like protein (ClSChE) from the common bed bug, Cimex lectularius.
      All three cholinesterase genes (Clac1, Clace2 and Clsce) have conserved motifs,
      including a catalytic triad, a choline-binding site and an acyl pocket.
      Phylogenetic analysis showed that ClAChE1 belongs to the insect AChE1 clade,
      whereas ClAChE2 belongs to the insect AChE2 clade. ClSChE was grouped into the
      clade containing all AChE1s, suggesting a paralogous relationship to ClAChE1.
      Transcription levels of Clace1 were higher than those of Clace2 in all tissues
      examined, including the central nervous system (CNS). In contrast, the Clsce
      transcript was not detected in the CNS but specifically found in the salivary
      gland at much higher levels (>3000-fold) than those of Clace1 and Clace2. Western
      blot analysis using anti-ClAChE antibodies, in conjunction with activity
      staining, revealed that ClAChE1 is more active than ClAChE2, whereas ClSChE has
      little enzyme activity. Three-dimensional structure modelling suggested that
      ClAChEs and ClSChE shared structural similarities, but had some differences in
      the residues forming the acyl pocket and oxyanion hole. The current findings
      should provide valuable insights into the evolution and functional
      diversification of insect cholinesterase.

PMID- 22136068
TI  - Twenty-four-week efficacy and safety of switching virologically suppressed HIV-1
      infected patients from nevirapine immediate release 200 mg twice daily to
      nevirapine extended release 400 mg once daily (TRANxITION).
AB  - OBJECTIVES: Once-daily (qd) antiretroviral therapies improve convenience and
      adherence. If found to be effective, nevirapine extended release (NVP XR) will
      confer this benefit. The TRANxITION trial examined the efficacy and safety of
      switching virologically suppressed patients from NVP immediate release (NVP IR)
      200 mg twice daily to NVP XR 400 mg qd. METHODS: An open-label, parallel-group,
      noninferiority, randomized (2:1 NVP XR:NVP IR) study was performed. Adult HIV-1
      infected patients receiving NVP IR plus a fixed-dose nucleoside reverse
      transcriptase inhibitor (NRTI) combination of lamivudine (3TC)/abacavir (ABC),
      tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV) with undetectable
      viral load (VL) were enrolled in the study. The primary endpoint was continued
      virological suppression with VL < 50 HIV-1 RNA copies/mL up to week 24
      (calculated using a time to loss of virological response algorithm). Cochran's
      statistic (background regimen adjusted) was used to test noninferiority. Adverse
      events (AEs) were recorded. RESULTS: Among 443 randomized patients, continued
      virological suppression was observed in 93.6% (276 of 295) of NVP XR- and 92.6%
      (137 of 148) of NVP IR-treated patients, an observed difference of 1% [95%
      confidence interval (CI) -4.3, 6.0] at 24 weeks of follow-up. Noninferiority
      (adjusted margin of -10%) of NVP XR to NVP IR was robust and further supported by
      SNAPSHOT analysis. Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3
      and 4 events were similar for the NVP XR and NVP IR groups (3.7 vs. 4.1%,
      respectively), although overall AEs were higher in the NVP XR group (75.6 vs.
      60.1% for the NVP-IR group). CONCLUSIONS: NVP XR administered once daily resulted
      in continued virological suppression at week 24 that was noninferior to that
      provided by NVP IR, with similar rates of moderate and severe AEs. The higher
      frequency of overall AEs with NVP XR may be a consequence of the open-label
      design.

PMID- 22136069
TI  - Intestinal levodopa infusion and COMT inhibition - a promising link.

PMID- 22136070
TI  - The genome sequence of the wine yeast VIN7 reveals an allotriploid hybrid genome
      with Saccharomyces cerevisiae and Saccharomyces kudriavzevii origins.
AB  - The vast majority of wine fermentations are performed principally by
      Saccharomyces cerevisiae. However, there are a growing number of instances in
      which other species of Saccharomyces play a predominant role. Interestingly, the
      presence of these other yeast species generally occurs via the formation of
      interspecific hybrids that contain genomic contributions from both S. cerevisiae
      and non-S. cerevisiae species. However, despite the large number of wine strains
      that are characterized at the genomic level, there remains limited information
      regarding the detailed genomic structure of hybrids used in winemaking. To
      address this, we describe the genome sequence of the thiol-releasing commercial
      wine yeast hybrid VIN7. VIN7 is shown to be an almost complete allotriploid
      interspecific hybrid that is comprised of a heterozygous diploid complement of S.
      cerevisiae chromosomes and a haploid Saccharomyces kudriavzevii genomic
      contribution. Both parental strains appear to be of European origin, with the S.
      cerevisiae parent being closely related to, but distinct from, the commercial
      wine yeasts QA23 and EC1118. In addition, several instances of chromosomal
      rearrangement between S. cerevisiae and S. kudriavzevii sequences were observed
      that may mark the early stages of hybrid genome consolidation.

PMID- 22136071
TI  - Prevalence of oral mucosal lesions in institutionalized elderly people in
      Mashhad, Northeast Iran.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of oral mucosal
      lesions in institutionalized elderly people in Mashhad, northeast of Iran.
      BACKGROUND: This study was conducted to assess the prevalence of oral lesions in
      the institutionalized elderly. METHODS: In this survey, we studied all of the
      nursing homes in Mashhad; a total of five encompassing 237 residents. The
      subjects were examined and lesions recorded in a designed checklist. T-test, chi
      square and Fisher's exact tests were used for the analysis. RESULTS: The mean age
      of the patients was 79.59 +/- 8.88. Ninety-eight per cent of cases had at least
      one oral mucosal lesion. The most common lesions were fissured tongue (66.5%),
      atrophic glossitis (48.8%), sublingual varicosity (42%) and xerostomia (38%).
      There was no significant difference in the prevalence of denture-related lesions
      (DRLs) between men and women (p > 0.05). Xerostomia was more prevalent in 70-79
      year-old than in 60-69-year-old subjects. No case of oral malignant lesion was
      detected. DISCUSSION: These findings revealed a higher prevalence of oral mucosal
      lesions in Mashhad city compared with other studies conducted in other major
      cities in Iran and abroad. The results emphasise the necessity of national
      programmes towards oral health promotion.

PMID- 22136072
TI  - QSAR study of 4-aryl-4H-chromenes as a new series of apoptosis inducers using
      different chemometric tools.
AB  - The apoptosis-inducing activity data of a series of 4-aryl-4H-chromenes based on
      three cell lines (human breast cancer cell line T47D, human non-smal cell lung
      cancer cell line H1299, and human colorectal cancer cell line DLD-1) have been
      subjected to quantitative structure-activity relationship (QSAR) analysis. A
      collection of chemometrics methods including multiple linear regression (MLR),
      factor analysis-based multiple linear regression (FA-MLR), principal component
      regression (PCR), and partial least squared combined with genetic algorithm for
      variable selection (GA-PLS) were employed to make connections between structural
      parameters and induction of apoptosis in three different cell lines. Models of
      high statistical qualities were obtained for each cell line using GA-PLS method.
      The results revealed that 2D autocorrelation descriptors and dipole moments as a
      quantum chemical parameter are important structural parameters that significantly
      influence the activity in all three types of cell lines. However, the determinant
      descriptors for activity of compounds in H1299 cell line were partly different
      from the two other cell lines, which might be deduce that the studied compounds
      induce apoptosis through a different mechanism of action.

PMID- 22136073
TI  - Can yoga improve fatigue in breast cancer patients? A systematic review.

PMID- 22136074
TI  - Ocular safety and pharmacokinetics study of FK506 suspension eye drops after
      corneal transplantation.
AB  - PURPOSE: The aim of this study was to investigate the sensitization,
      pharmacokinetics, and absorption of FK506 after corneal transplantation. METHODS:
      New Zealand albino rabbits were divided into normal and corneal transplantation
      groups. Each group was divided into 5 subgroups--saline, blank matrix, high-dose,
      medium-dose, and low-dose, respectively. There were 10 rabbits in each subgroup.
      One drop (25 MUL) of FK506 was administered topically to both eyes of the rabbits
      4 times daily for 30 days. Thirty days later, 5 rabbits of each subgroup were
      sacrificed after the administration of the last dose. Both eyes were enucleated;
      the left eye was used for pathologic examination and the right eye for the
      determination of FK506 distribution. The other 5 rabbits in each subgroup were
      sacrificed 14 days after the former 5 rabbits were sacrificed, and their eyes
      were enucleated for pathologic examination and tissue distribution determination
      as the former 5 rabbits in each subgroup (the second batch). RESULTS: Fluorescein
      staining and local ocular reaction provided evidence that there were no
      significant differences between control and FK506-instilled eyes in the rabbit
      model at any of the tested doses. Histologic examination revealed no ocular
      abnormality in the rabbits instilled with any doses of FK506 eyedrop. The peak
      serum concentration (C(max)) of systemic absorption ranged from 4.31+/-0.79 ng/mL
      to 14.89+/-6.85 ng/mL. CONCLUSION: Our study suggests that up to 0.1% FK506
      administered 4 times a day (q.i.d.) topically is safe for the rabbit eye.
      However, further safety studies are required in view of systemic adverse effects.

PMID- 22136078
TI  - Prospective use of subtraction ictal SPECT coregistered to MRI (SISCOM) in
      presurgical evaluation of epilepsy.
AB  - PURPOSE: In patients with drug-refractory focal epilepsy, nonlesional magnetic
      resonance imaging (MRI) or discordant data of presurgical standard investigations
      leads to failure generating a sufficient hypothesis for electrode implantation or
      epilepsy surgery. The seizure-onset zone can be further investigated by
      subtraction ictal single-photon emission computed tomography (SPECT) coregistered
      to MRI (SISCOM). This is an observational study of a large consecutive cohort of
      patients undergoing prospective SISCOM to generate hypothesis for electrode
      implantation or site of epilepsy surgery. METHODS: One hundred seventy-five
      consecutive patients undergoing presurgical evaluation with either nonlesional
      MRI or discordant data of standard investigations preventing the generation of
      hypothesis for seizure onset were evaluated with SISCOM. Results were compared to
      gold standard for seizure onset detection, either electrocorticography (ECoG)
      and/or postoperative outcome. KEY FINDINGS: One hundred thirty patients had
      successful SPECT injection. Hypothesis for electrode implantation/site of surgery
      was generated in 74 patients. Forty patients had gold standard comparison. Twenty
      eight patients underwent resective surgery. SISCOM was concordant to site of
      surgery in 82%. An additional 12 patients underwent invasive EEG monitoring but
      were not suitable for surgery. SISCOM was concordant multifocal in 75%. Two years
      postsurgical follow-up of 26 patients showed favorable outcome in 22 (Engel class
      I and class II). SIGNIFICANCE: SISCOM is a highly valuable diagnostic tool to
      localize the seizure-onset zone in nonlesional and extratemporal epilepsies.
      Outcome in this patient group was unexpectedly good, even in patients with
      nonlesional MRI. The high correlation with ECoG and site of successful surgery is
      a strong indicator that outcome prediction in this patient group should be
      adapted accordingly, which may encourage more patients to undergo electrode
      implantation and subsequent successful surgery. Statistical analysis showed that
      SISCOM with shorter duration of seizures, focal seizures, and lesional MRI was
      more likely to generate implantation hypothesis.

PMID- 22136077
TI  - Determinants of health-related quality of life in pharmacoresistant epilepsy:
      results from a large multicenter study of consecutively enrolled patients using
      validated quantitative assessments.
AB  - PURPOSE: To evaluate the relative contribution of demographic and epilepsy
      related variables, depressive symptoms, and adverse effects (AEs) of
      antiepileptic drugs (AEDs) to health-related quality of life (HRQOL) in adults
      with pharmacoresistant epilepsy. METHODS: Individuals with epilepsy whose
      seizures failed to respond to at least one AED were enrolled consecutively at 11
      tertiary referral centers. HRQOL was assessed by the Quality of Life in Epilepsy
      Inventory-31 (QOLIE-31), AEs by the Adverse Event Profile (AEP), and depressive
      symptoms by the Beck Depression Inventory-II (BDI-II). Multivariate linear
      regression models were used to identify variables associated with QOLIE-31 total
      score and subscale scores. KEY FINDINGS: Of 933 enrolled individuals aged 16
      years or older, 809 (87%) were able to complete the self-assessment instruments
      and were included in the analysis. Overall, 61% of the variance in QOLIE-31
      scores was explained by the final model. The strongest predictors of HRQOL were
      AEP total scores (beta = -0.451, p < 0.001) and BDI-II scores (beta = -0.398, p <
      0.001). These factors were also the strongest predictors of scores in each of the
      seven QOLIE-31 subscales. Other predictors of HRQOL were age (beta = -0.060, p =
      0.008), lack of a driving license (beta = -0.053, p = 0.018), pharmacoresistance
      grade, with higher HRQOL in individuals who had failed only one AED (beta =
      0.066, p = 0.004), and location of the enrolling center. Epilepsy-related
      variables (seizure frequency, occurrence of tonic-clonic seizures, age of
      epilepsy onset, disease duration) and number of AEDs had no significant
      predictive value on HRQOL. The AEP total score was the strongest negative
      predictor of HRQOL in the subgroup of 362 patients without depressive symptoms
      (BDI-II score <10), but even in this subgroup the BDI-II score was retained as a
      significant predictor. SIGNIFICANCE: In individuals with pharmacoresistant
      epilepsy, AEs of medication and depressive symptoms are far more important
      determinants of HRQOL than seizures themselves. When seizure freedom cannot be
      achieved, addressing depressive comorbidity and reducing the burden of AED
      toxicity is likely to be far more beneficial than interventions aimed at reducing
      the frequency of seizures.

PMID- 22136079
TI  - Valproate effects on generalized spike-wave discharges and photoparoxysmal
      response.

PMID- 22136080
TI  - Understanding community perceptions, social norms and current practice related to
      respiratory infection in Bangladesh during 2009: a qualitative formative study.
AB  - BACKGROUND: Respiratory infections are the leading cause of childhood deaths in
      Bangladesh. Promoting respiratory hygiene may reduce infection transmission. This
      formative research explored community perceptions about respiratory infections.
      METHODS: We conducted 34 in-depth interviews and 16 focus group discussions with
      community members and school children to explore respiratory hygiene related
      perceptions, practices, and social norms in an urban and a rural setting. We
      conducted unstructured observations on respiratory hygiene practices in public
      markets. RESULTS: Informants were not familiar with the term "respiratory
      infection"; most named diseases that had no relation to respiratory dysfunction.
      Informants reported that their community identified a number of 'good behaviors'
      related to respiratory hygiene, but they also noted, and we observed, that very
      few people practiced these. All informants cited hot/cold weather changes or
      using cold water as causes for catching cold. They associated transmission of
      respiratory infections with close contact with a sick person's breath, cough
      droplets, or spit; sharing a sick person's utensils and food. Informants
      suggested that avoiding such contact was the most effective method to prevent
      respiratory infection. Although informants perceived that handwashing after
      coughing or sneezing might prevent illness, they felt this was not typically
      feasible or practical. CONCLUSION: Community perceptions of respiratory
      infections include both concerns with imbalances between hot and cold, and with
      person-to-person transmission. Many people were aware of measures that could
      prevent respiratory infection, but did not practice them. Interventions that
      leverage community understanding of person-to-person transmission and that
      encourage the practice of their identified 'good behaviors' related to
      respiratory hygiene may reduce respiratory disease transmission.

PMID- 22136081
TI  - Nanostructured Al-ZnO/CdSe/Cu2O ETA solar cells on Al-ZnO film/quartz glass
      templates.
AB  - The quartz/Al-ZnO film/nanostructured Al-ZnO/CdSe/Cu2O extremely thin absorber
      solar cell has been successfully realized. The Al-doped ZnO one-dimensional
      nanostructures on quartz templates covered by a sputtering Al-doped ZnO film was
      used as the n-type electrode. A 19- to 35-nm-thin layer of CdSe absorber was
      deposited by radio frequency magnetron sputtering, coating the ZnO
      nanostructures. The voids between the Al-ZnO/CdSe nanostructures were filled with
      p-type Cu2O, and therefore, the entire assembly formed a p-i-n junction. The cell
      shows the energy conversion efficiency as high as 3.16%, which is an interesting
      option for developing new solar cell devices.PACS: 88.40.jp; 73.40.Lq; 73.50.Pz.

PMID- 22136082
TI  - Safety and efficacy of tinea pedis and onychomycosis treatment in people with
      diabetes: a systematic review.
AB  - BACKGROUND: Effective treatment of tinea pedis and onychomycosis is crucial for
      patients with diabetes as these infections may lead to foot ulcers and secondary
      bacterial infections resulting in eventual lower limb amputation. Although
      numerous studies have assessed the effectiveness of antifungal drug and treatment
      regimens, most exclude patients with diabetes and examine otherwise healthy
      individuals. While these studies are useful, results cannot necessarily be
      extrapolated to patients with diabetes. The purpose of this study was to
      therefore identify the best evidence-based treatment interventions for tinea
      pedis or onychomycosis in people with diabetes. METHODS: The question for this
      systemic review was: 'what evidence is there for the safety and/or efficacy of
      all treatment interventions for adults with tinea pedis and/or onychomycosis in
      people with diabetes'? A systematic literature search of four electronic
      databases (Scopus, EbscoHost, Ovid, Web of Science) was undertaken (6/1/11). The
      primary outcome measure for safety was self-reported adverse events likely to be
      drug-related, while the primary outcome measures assessed for 'efficacy' were
      mycological, clinical and complete cure. RESULTS: The systematic review
      identified six studies that examined the safety and/or efficacy of treatment
      interventions for onychomycosis in people with diabetes. No studies were
      identified that examined treatment for tinea pedis. Of the studies identified,
      two were randomised controlled trials (RCTs) and four were case series. Based on
      the best available evidence identified, it can be suggested that oral terbinafine
      is as safe and effective as oral itraconazole therapy for the treatment of
      onychomycosis in people with diabetes. However, efficacy results were found to be
      poor. CONCLUSIONS: This review indicates that there is good evidence (Level II)
      to suggest oral terbinafine is as safe and effective as itraconazole therapy for
      the treatment of onychomycosis in people with diabetes. Further research is
      needed to establish the evidence for other treatment modalities and treatment for
      tinea pedis for people with diabetes. Future efforts are needed to improve the
      efficacy of treatment intervention.

PMID- 22136083
TI  - Determination of cryoprotectant for magnetic cryopreservation of dental pulp
      tissue.
AB  - Dental pulp, covered with dental hard tissue, is a promising source of
      mesenchymal stem cells and osteoprogenitor cells for regenerative medicine. Our
      previous studies showed that 73% of dental pulp cells isolated from magnetically
      cryopreserved teeth where their viability, morphology, and expression of stem
      cell surface markers were similar to the cells isolated from fresh teeth,
      suggesting that magnetic cryopreservation is an applicable method for intact
      tooth as well as dental pulp tissue banking. However, the cryoprotectant,
      concentration, contact surface, and equilibration time for magnetic
      cryopreservation of dental pulp require optimization. In addition, the integrity
      and viability of post-thawed dental pulp with and without dental hard tissue
      covering after magnetic cryopreservation were investigated. Lower concentration
      of the cryoprotectant (5% dimethyl sulfoxide [DMSO]) and shorter preequilibration
      time are required for magnetic cryopreservation compared with the conventional
      cryopreservation method. The structure of at least 33% of post-thawed pulp with
      dental hard tissue from the open end remained intact where >80% of cells were
      viable. The addition of the cryoprotectant additive trehalose did not replace or
      improve DMSO's efficacy for magnetic cryopreservation of dental pulp or intact
      tooth. Tooth banking for transplantation provides an alternative treatment to
      replace missing teeth. The optimized cryoprotectant conditions for dental pulp
      tissue during magnetic cryopreservation should lead to more satisfactory outcomes
      in clinical applications such as autotransplantation and the isolation and
      expansion of dental pulp stem cells for tissue repair.

PMID- 22136084
TI  - Cognition and Emotion over twenty-five years.
AB  - In the 25 years since its foundation, Cognition and Emotion has become a leading
      psychological journal of research on emotion. Here we review some of the ways in
      which this has occurred. Questions have included how parallel systems of
      cognition and emotion can operate in emotion regulation and psychological
      therapies (including the issue of free will), how the cognitive approach to
      emotion works, how emotion affects attention, memory, and decision making, and
      how emotion research is moving beyond the individual mind into the space of the
      interpersonal.

PMID- 22136090
TI  - The kallikrein/kinin system in ocular function.
AB  - The kallikrein/kinin system uses two distinct serine proteases, plasma kallikrein
      and tissue kallikrein, to yield bradykinin and Lys-bradykinin (kallidin) from
      specific substrate kininogens. The kallikrein/kinin system is known to have a
      role in contact-activated coagulation mechanisms and in inflammatory responses,
      and recently has been shown to contribute to homeostatic and protective
      mechanisms in the cardiovascular and renal systems. This article reviews current
      knowledge of the ocular kallikrein/kinin system within the context of proposed
      roles for this system in other important organs and tissues. All components of
      the kallikrein/kinin system are present in the eye and are positioned to
      participate in key ocular functions. Plasma kallikrein binds to vascular
      endothelium and generates bradykinin, which may contribute to regulation of
      ocular blood flow, and, in excess, has been implicated in the pathogenesis of
      retinal edema in patients with proliferative diabetic retinopathy. Tissue
      kallikrein is expressed in retina, ciliary muscle, and trabecular meshwork cells
      and could be a significant factor in the protective mechanism of ischemic
      preconditioning, and in the modulation of aqueous dynamics. Improved
      understanding of the role of plasma and tissue kallikreins and kinins in such
      processes has the potential to identify significant new targets for the therapy
      of ocular dysfunction.

PMID- 22136089
TI  - Comparison of human ocular distribution of bimatoprost and latanoprost.
AB  - PURPOSE: This study investigated the ocular distribution of bimatoprost,
      latanoprost, and their acid hydrolysis products in the aqueous humor, cornea,
      sclera, iris, and ciliary body of patients treated with a single topical dose of
      0.03% bimatoprost or 0.005% latanoprost for understanding concentration-activity
      relationships. METHODS: Thirty-one patients undergoing enucleation for an
      intraocular tumor not affecting the anterior part of the globe were randomized to
      treatment with bimatoprost or latanoprost at 1, 3, 6 or 12 h prior to surgery.
      Concentrations of bimatoprost, bimatoprost acid, latanoprost, and latanoprost
      acid in the human aqueous and ocular tissues were measured using liquid
      chromatography tandem mass spectrometry. RESULTS: Following topical
      administration, intact bimatoprost was distributed in human eyes with a rank
      order of cornea/sclera >iris/ciliary body >aqueous humor. Bimatoprost acid was
      also detected in these tissues, where its low levels in the cornea relative to
      that of latanoprost acid indicated that bimatoprost hydrolysis was limited.
      Latanoprost behaved as a prodrug that entered eyes predominantly via the corneal
      route. Levels of latanoprost acid were distributed as cornea >>aqueous
      humor>iris>sclera>ciliary body. CONCLUSIONS: Our study provided experimental
      evidence that levels of bimatoprost in relevant ocular tissues, and not only
      aqueous humor, are needed to understand the mechanisms by which bimatoprost
      lowers intraocular pressure (IOP) in human subjects. The data suggest that
      bimatoprost reached the target tissues favoring the conjunctival/scleral
      absorption route. Findings of intact bimatoprost in the target ciliary body
      indicated its direct involvement in reducing IOP. However, bimatoprost acid may
      have only a limited contribution on the basis that bimatoprost has
      greater/similar IOP-lowering efficacy than latanoprost, yet bimatoprost acid
      levels were a fraction of latanoprost acid levels in the aqueous humor and cornea
      and only sporadically detectable in the ciliary body. In this report, human
      ocular tissues were examined concurrently with aqueous humor for the in vivo
      distribution of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid.

PMID- 22136091
TI  - An open-label naturalistic pilot study of acamprosate in youth with autistic
      disorder.
AB  - To date, placebo-controlled drug trials targeting the core social impairment of
      autistic disorder (autism) have had uniformly negative results. Given this, the
      search for new potentially novel agents targeting the core social impairment of
      autism continues. Acamprosate is U.S. Food and Drug Administration-approved drug
      to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid
      and glutamate neurotransmission. This study describes our initial open-label
      experience with acamprosate targeting social impairment in youth with autism. In
      this naturalistic report, five of six youth (mean age, 9.5 years) were judged
      treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks
      (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only
      mild gastrointestinal adverse effects noted in three (50%) subjects.

PMID- 22136092
TI  - The pharmacoepidemiology of antipsychotic medications for Canadian children and
      adolescents: 2005-2009.
AB  - OBJECTIVE: To describe the frequency and trends of use of antipsychotics in
      Canadian children and adolescents from 2005 to 2009. METHODS: We performed
      analyses on the IMS Brogan databases on drug recommendation (prescribed drug)
      frequency, reasons for recommendations (therapeutic indication), and duration of
      use of antipsychotics, psychostimulants, and selective serotonin reuptake
      inhibitors (SSRIs) for Canadian children between 2005 and 2009. Changes in the
      number of and reasons for drug recommendations over the 5-year period are
      highlighted by using descriptive statistics. RESULTS: Antipsychotic drug
      recommendations by all specialists for children increased by 114% from 2005 to
      2009. In contrast, psychostimulant and SSRI drug recommendations increased by 36%
      and 44%, respectively. The majority of antipsychotic drug recommendations were
      for second-generation antipsychotics (SGAs). Attention-deficit/hyperactivity
      disorder (ADHD) was the most common therapeutic indication associated with an SGA
      recommendation. Antipsychotic drug recommendations for children with ADHD more
      than tripled between 2005 and 2009. The average duration of antipsychotic use in
      children varied by drug and age group. For risperidone, median duration of use
      was 90 days in children aged 1-6, 180 days in children aged 7-12, and 200 days in
      children aged 13-18. CONCLUSION: The use of antipsychotics in Canadian children
      greatly increased from 2005 to 2009. Comparison of antipsychotic data with
      psychostimulant and SSRI data shows that there has been a disproportionate
      increase in antipsychotic use over this interval, despite the lack of approval
      for pediatric use by Health Canada. Postmarketing surveillance activities of
      antipsychotic use in children appear appropriate.

PMID- 22136093
TI  - Risperidone and double incontinence in a child with autism.

PMID- 22136095
TI  - Relaxation drinks and their use in adolescents.
AB  - OBJECTIVES: A new class of beverages called relaxation drinks advertises calming
      effects and an easy way to wind down when life gets stressful. This article
      examines these drinks in the context of their use in adolescents. METHODS: A
      review of the literature relevant to relaxation drinks and their functional
      ingredients was conducted. RESULTS: The beverages contain ingredients such as
      melatonin, valerian, kava, tryptophan, and other products traditionally thought
      to play a role in sleep, sedation, or neurocognitive function. Studies of the
      efficacy and safety of these supplements are limited and many have significant
      methodological limitations. Despite appropriate warnings placed on the labels of
      relaxation drinks, marketing is cleverly designed to appeal to young consumers
      and often evokes the experiences produced by alcohol and drug use. CONCLUSION:
      Although moderate consumption of these beverages by healthy individuals is likely
      safe, an objective reduction in stress is improbable and associated adverse
      effects are possible.

PMID- 22136094
TI  - Dose effects and comparative effectiveness of extended release dexmethylphenidate
      and mixed amphetamine salts.
AB  - OBJECTIVE: To compare the dose effects of long-acting extended-release
      dexmethylphenidate (ER d-MPH) and ER mixed amphetamine salts (ER MAS) on
      attention-deficit/hyperactivity disorder (ADHD) symptom dimensions, global and
      specific impairments, and common adverse events associated with stimulants.
      METHODS: Fifty-six children and adolescents with ADHD participated in an 8-week,
      double-blind, crossover study comparing ER d-MPH (10, 20, 25-30 mg) and ER MAS
      (10, 20, 25-30) with a week of randomized placebo within each drug period.
      Efficacy was assessed with the ADHD Rating Scale-IV (ADHD-RS-IV), whereas global
      and specific domains of impairment were assessed with the Clinical Global
      Impressions Severity and Improvement Scales and the parent-completed Weiss
      Functional Impairment Scale, respectively. Insomnia and decreased appetite,
      common stimulant-related adverse events, were measured with the parent-completed
      Stimulant Side Effects Rating Scale. RESULTS: Both ER d-MPH and ER MAS were
      associated with significant reductions in ADHD symptoms. Improvement in Total
      ADHD and Hyperactivity/Impulsivity symptoms were strongly associated with
      increasing dose, whereas improvements in Inattentive symptoms were only
      moderately associated with dose. About 80% demonstrated reliable change on ADHD
      RS-IV at the highest dose level of ER MAS compared with 79% when receiving ER d
      MPH. Decreased appetite and insomnia were more common at higher dose levels for
      both stimulants. Approximately 43% of the responders were preferential responders
      to only one of the stimulant formulations. CONCLUSIONS: Dose level, rather than
      stimulant class, was strongly related to medication response.

PMID- 22136096
TI  - Co-morbid disruptive behavior disorder and aggression predict functional outcomes
      and differential response to risperidone versus divalproex in pharmacotherapy for
      pediatric bipolar disorder.
AB  - OBJECTIVE: Co-morbid diagnoses, such as disruptive behavior disorders (DBDs) and
      high levels of aggression, are extremely common among youth with pediatric
      bipolar disorder (PBD) and may interfere with treatment response; however, they
      have rarely been examined as predictors of response to pharmacotherapy. The
      current study examines co-morbid DBD and aggression prospectively as predictors
      of pharmacotherapy outcome, as well as potential moderators of response to a
      specific medication (risperidone vs. divalproex), among children with PBD.
      METHODS: Data are from a prospective 6-week double-blind, placebo-controlled,
      randomized outpatient medication treatment trial of risperidone versus divalproex
      for manic episodes in 65 children 8-18 with PBD. Outcome measures were
      administered at pretest, post-test, and weekly during the 6 weeks of treatment.
      Mixed-effects regression models were used to examine pharmacotherapy response.
      RESULTS: Results indicated that youth with co-morbid DBD experienced greater
      improvement in manic symptoms in response to risperidone versus divalproex,
      whereas youth with non-co-morbid DBD experienced similar trajectories of symptom
      improvement in both medication groups. In addition, the non-DBD group experienced
      greater improvement in global functioning over time as compared with youth with
      co-morbid-DBD, and this gap increased over the course of treatment. Results also
      indicated that high-aggression youth experienced worse global functioning by end
      treatment versus low-aggression youth. CONCLUSIONS: In conclusion, a co-morbid
      diagnosis of DBD and/or high levels of aggressive symptoms in youth with PBD may
      be important clinical predictors of variation in treatment response to
      pharmacotherapy. These findings may help researchers and clinicians develop
      tailored treatment approaches that optimize symptom and functional outcomes.

PMID- 22136097
TI  - Buspirone for bruxism in a child with pervasive developmental disorder-not
      otherwise specified.

PMID- 22136098
TI  - Two-year follow-up of cognitive functions in schizophrenia spectrum disorders of
      adolescent patients treated with electroconvulsive therapy.
AB  - OBJECTIVE: The aim of the current study was to investigate the long-term
      cognitive effects of electroconvulsive therapy (ECT) in a sample of adolescent
      patients in whom schizophrenia spectrum disorders were diagnosed. METHODS: The
      sample was composed of nine adolescent subjects in whom schizophrenia or
      schizoaffective disorder was diagnosed according to DSM-IV-TR criteria on whom
      ECT was conducted (ECT group) and nine adolescent subjects matched by age,
      socioeconomic status, and diagnostic and Positive and Negative Syndrome Scale
      (PANSS) total score at baseline on whom ECT was not conducted (NECT group).
      Clinical and neuropsychological assessments were carried out at baseline before
      ECT treatment and at 2-year follow-up. RESULTS: Significant differences were
      found between groups in the number of unsuccessful medication trials. No
      statistically significant differences were found between the ECT group and the
      NECT group in either severity as assessed by the PANSS, or in any cognitive
      variables at baseline. At follow-up, both groups showed significant improvement
      in clinical variables (subscales of positive, general, and total scores of PANSS
      and Clinical Global Impressions-Improvement). In the cognitive assessment at
      follow-up, significant improvement was found in both groups in the semantic
      category of verbal fluency task and digits forward. However, no significant
      differences were found between groups in any clinical or cognitive variable at
      follow-up. Repeated measures analysis found no significant interaction of
      time*group in any clinical or neuropsychological measures. CONCLUSIONS: The
      current study showed no significant differences in change over time in clinical
      or neuropsychological variables between the ECT group and the NECT group at 2
      year follow-up. Thus, ECT did not show any negative influence on long-term
      neuropsychological variables in our sample.

PMID- 22136099
TI  - Interferential and burst-modulated biphasic pulsed currents yield greater
      muscular force than Russian current.
AB  - OBJECTIVE: Previous data regarding neuromuscular electrical stimulation (NMES)
      have suggested that muscle torque production with interferential current (IFC) is
      inferior to Russian current; however, waveform parameters specific and critical
      to NMES were inconsistent, making interpretation of previous findings precarious.
      The purpose of this investigation was to compare muscle force production of three
      electrical stimulating waveforms when using equivalent stimulus parameters.
      DESIGN: The percent of maximal voluntary isometric knee extensor force (%MVIF)
      elicited using interferential, Russian, and burst-modulated biphasic pulsed
      currents were compared in 23 healthy college-aged subjects. A repeated measures
      single factor design in a university laboratory setting was used. RESULTS: A
      significant effect for waveform used was noted. Data showed significantly greater
      %MVIF of the knee extensors were obtained using IFC or burst-modulated BP current
      versus conventional Russian current. CONCLUSIONS: The results of this
      investigation suggest that IFC and burst-modulated BP current are viable waveform
      options for purposes of eliciting muscle force. These findings offer significant
      new evidence with strong clinical implications when selecting waveform parameters
      for elicitation of muscle force for NMES.

PMID- 22136100
TI  - Bioactive healthy components of bulgur.
AB  - Bulgur has been one of the most important traditional Durum wheat products in
      Turkey and Middle Eastern countries for ages. The objective of this study was to
      reveal the composition of some healthy components of industrial bulgur samples
      produced in Turkey. Total starch, resistant starch, dietary fibre and total
      phenolic contents and their high-performance liquid chromatography (HPLC) profile
      and antioxidant capacity of bulgur samples using 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical
      scavenging activity methods were investigated. The results showed that total
      dietary fibre ranged between 5.8 +/- 0.7 and 8.2 +/- 0.7% and resistant starch
      between 2.1 +/- 0.2 and 2.8 +/- 0.2%. Moreover, phenolic content with an average
      of 59.5 +/- 5.2 mg Gallic acid/100 g dry matter and a moderate level of
      antioxidant capacity with an average of 22.2 +/- 2.4% DPPH scavenging activity
      and 563.3 +/- 60.7 MUmol Trolox Equivalent Antioxidant Capacity/100 g dry matter
      of ABTS scavenging activity add value to the health benefits of bulgur product.

PMID- 22136101
TI  - Sonogashira coupling reactions of bromomaleimides: route to alkyne/cis
      alkene/alkyl maleimides: synthesis of luffarin X and cacospongionolide C.
AB  - Palladium-catalyzed Sonogashira coupling reaction of bromomaleimides with a
      diverse range of terminal alkynes has been demonstrated to furnish the
      corresponding alkynylmaleimides in very good yields. This coupling reaction
      followed by selective reduction of the triple bond to single bond have been
      utilized as the decisive steps to accomplish the first total synthesis of natural
      products (+/-)-luffarin X and (+/-)-cacospongionolide C.

PMID- 22136102
TI  - Correlation of magnesium levels in cord blood and maternal serum among pre
      eclamptic pregnant women treated with magnesium sulfate.
AB  - AIM: The aim of this study was to determine the correlation between cord blood
      and maternal serum magnesium levels among pre-eclamptic pregnant women treated
      with magnesium sulfate. MATERIALS AND METHODS: A total of 36 pregnant women,
      >28weeks' gestation, diagnosed with pre-eclampsia and treated with magnesium
      sulfate (MgSO(4) ), were enrolled. Maternal and umbilical cord blood samples were
      obtained immediately after delivery and sent for determination of magnesium and
      calcium levels. RESULTS:   Mean maternal age was 27.4+/-6.4years and mean
      gestational age was 38.1+/-1.8weeks. Most were diagnosed with pre-eclampsia
      (94.5%), others had HELLP syndrome. Mean total MgSO(4) the women received was
      14.4+/-6.0g and mean duration of treatment was 5.1+/-3.3h. Mean maternal serum
      and cord blood magnesium levels were 2.2+/-0.4 and 1.8+/-0.3mmol/L, respectively.
      Maternal magnesium and calcium levels showed significant positive correlation
      with their levels in cord blood (P<0.001). Significant positive correlation was
      found between total dose as well as duration of MgSO4 and maternal and cord blood
      magnesium levels (P<0.001) but was inversely correlated with maternal and cord
      blood calcium levels. CONCLUSIONS: Maternal serum magnesium and calcium levels
      were correlated with cord blood levels in pre-eclamptic pregnant women who
      received MgSO4 therapy.

PMID- 22136103
TI  - Oral versus intravenous antibiotics in treatment of paediatric febrile
      neutropenia.
AB  - The purpose of this study is to determine whether, in low-risk febrile
      neutropenic paediatric populations, oral antibiotics are as effective as
      intravenous antibiotics in obtaining resolution of the febrile neutropenic
      episode. A comprehensive literature search of MEDLINE, EMBASE and CENTRAL
      identified prospective, randomised controlled trials comparing oral antibiotics
      with intravenous antibiotics in the treatment of febrile neutropenic episodes in
      low-risk paediatric oncology patients. Outcomes assessed were mortality, rate of
      treatment failure, length of the febrile neutropenic episode and adverse events.
      The random effects model was used to calculate risk ratios (RRs) for dichotomous
      data and mean difference with standard deviation for continuous data. Seven
      trials were included in the overall analysis, which included 934 episodes of
      febrile neutropenia in 676 patients aged between 9 months and 20 years. The
      overall treatment failure rates were not significantly different between oral and
      intravenous antibiotics (RR: 1.02, 95% confidence interval 0.78-1.32, P= 0.91).
      In carefully selected low-risk febrile neutropenic children, empiric treatment
      with oral antibiotics is a safe and effective alternative to intravenous
      antibiotics as they lower the cost of treatment as well as psychosocial burden on
      these children and their families.

PMID- 22136104
TI  - Tackling alcohol misuse: purchasing patterns affected by minimum pricing for
      alcohol.
AB  - BACKGROUND: Alcohol consumption is associated with a range of health and social
      harms that increase with the level of consumption. Policy makers are interested
      in effective and cost-effective interventions to reduce alcohol consumption and
      associated harms. Economic theory and research evidence demonstrate that
      increasing price is effective at the population level. Price interventions that
      target heavier consumers of alcohol may be more effective at reducing alcohol
      related harms with less impact on moderate consumers. Minimum pricing per unit of
      alcohol has been proposed on this basis but concerns have been expressed that
      'moderate drinkers of modest means' will be unfairly penalized. If those on low
      incomes are disproportionately affected by a policy that removes very cheap
      alcohol from the market, the policy could be regressive. The effect on
      households' budgets will depend on who currently purchases cheaper products and
      the extent to which the resulting changes in prices will impact on their demand
      for alcohol. This paper focuses on the first of these points. OBJECTIVE: This
      paper aims to identify patterns of purchasing of cheap off-trade alcohol
      products, focusing on income and the level of all alcohol purchased. METHOD:
      Three years (2006-08) of UK household survey data were used. The Expenditure and
      Food Survey provides comprehensive 2-week data on household expenditure.
      Regression analyses were used to investigate the relationships between the
      purchase of cheap off-trade alcohol, household income levels and whether the
      household level of alcohol purchasing is categorized as moderate, hazardous or
      harmful, while controlling for other household and non-household characteristics.
      Predicted probabilities and quantities for cheap alcohol purchasing patterns were
      generated for all households. RESULTS: The descriptive statistics and regression
      analyses indicate that low-income households are not the predominant purchasers
      of any alcohol or even of cheap alcohol. Of those who do purchase off-trade
      alcohol, the lowest income households are the most likely to purchase cheap
      alcohol. However, when combined with the fact that the lowest income households
      are the least likely to purchase any off-trade alcohol, they have the lowest
      probability of purchasing cheap off-trade alcohol at the population level.
      Moderate purchasing households in all income quintiles are the group predicted as
      least likely to purchase cheap alcohol. The predicted average quantity of low
      cost off-trade alcohol reveals similar patterns. CONCLUSION: The results suggest
      that heavier household purchasers of alcohol are most likely to be affected by
      the introduction of a 'minimum price per unit of alcohol' policy. When we focus
      only on those households that purchase off-trade alcohol, lower income households
      are the most likely to be affected. However, minimum pricing in the UK is
      unlikely to be significantly regressive when the effects are considered for the
      whole population, including those households that do not purchase any off-trade
      alcohol. Minimum pricing will affect the minority of low-income households that
      purchase off-trade alcohol and, within this group, those most likely to be
      affected are households purchasing at a harmful level.

PMID- 22136105
TI  - Alcohol policy and taxation in South Africa: an examination of the economic
      burden of alcohol tax.
AB  - BACKGROUND: Alcohol consumption accounts for over 4% of the global burden of
      disease and an even higher figure in developing countries. Several policies have
      been proposed to curb the negative impact of alcohol misuse. Apart from South
      Africa, which has witnessed a rapid development in alcohol policy, such policies
      are poorly developed in most African countries. South Africa uses taxation as a
      policy lever, in line with international evidence, to reduce alcohol consumption.
      However, the problem of alcohol abuse still exists. OBJECTIVE: The objective of
      this article is to present an analysis of alcohol tax incidence for the first
      time in South Africa. This was done for each category of alcohol tax (wines,
      spirits, beer and traditional brew [sorghum beer]) and for alcohol tax as a
      whole. The paper also uses the results to point to the areas where a greater
      understanding of the issues surrounding alcohol abuse needs to be developed.
      METHODS: Data were drawn from the 2005/06 South African Income and Expenditure
      Survey. Reported expenditures on alcohol beverages were used to obtain the tax
      component paid by households. This was done under certain assumptions relating to
      alcohol content and the price per litre of alcohol. Per adult equivalent
      consumption expenditure was used as the measure of relative living standards and
      concentration curves and Kakwani indices to assess relative progressivity of
      alcohol taxes. Statistical dominance tests were also performed. RESULTS: Most
      sorghum beer and malt beer drinkers were in the poorer quintiles. The reverse was
      the case for wines and spirits. Overall, alcohol tax in South Africa was
      regressive (Kakwani index -0.353). The individual categories were found to be
      regressive. The most regressive tax was that on sorghum beer (Kakwani index 
      1.01); the least regressive was that on spirits (Kakwani index -0.09), although
      this was not statistically significant at conventional levels. These results were
      confirmed by the test of dominance. CONCLUSION: In South Africa, there has been a
      renewed interest in addressing the problem of rising alcohol abuse, but the
      extent to which this will translate into meaningful policies is unclear. The use
      of an excise tax is increasingly being recognized by economists as a way to get
      around some of the negative effects of abusive alcohol consumption. However, this
      study indicates that alcohol taxes are regressive in South Africa.

PMID- 22136106
TI  - Kinetics of calcium phosphate nucleation and growth on calcite: implications for
      predicting the fate of dissolved phosphate species in alkaline soils.
AB  - Unraveling the kinetics of calcium orthophosphate (Ca-P) precipitation and
      dissolution is important for our understanding of the transformation and mobility
      of dissolved phosphate species in soils. Here we use an in situ atomic force
      microscopy (AFM) coupled with a fluid reaction cell to study the interaction of
      phosphate-bearing solutions with calcite surfaces. We observe that the mineral
      surface-induced formation of Ca-P phases is initiated with the aggregation of
      clusters leading to the nucleation and subsequent growth of Ca-P phases on
      calcite, at various pH values and ionic strengths relevant to soil solution
      conditions. A significant decrease in the dissolved phosphate concentration
      occurs due to the promoted nucleation of Ca-P phases on calcite surfaces at
      elevated phosphate concentrations and more significantly at high salt
      concentrations. Also, kinetic data analyses show that low concentrations of
      citrate caused an increase in the nucleation rate of Ca-P phases. However, at
      higher concentrations of citrate, nucleation acceleration was reversed with much
      longer induction times to form Ca-P nuclei. These results demonstrate that the
      nucleation-modifying properties of small organic molecules may be scaled up to
      analyze Ca-P dissolution-precipitation processes that are mediated by a more
      complex soil environment. This in situ observation, albeit preliminary, may
      contribute to an improved understanding of the fate of dissolved phosphate
      species in diverse soil systems.

PMID- 22136107
TI  - Indian herbal medicines in the treatment of liver diseases: problems and
      promises.
AB  - Plant drugs are known to play a major role in the management of liver diseases.
      There are many plants and their extracts that have been shown to possess
      hepatoprotective activities. There are more than 300 preparations in Indian
      system of medicine for the treatment of jaundice and chronic liver diseases.
      About 600 commercial herbal formulations with claimed hepatoprotective activity
      are being sold all over the globe. The active phytochemical fraction that imparts
      hepatoprotective activity has been identified in many plants. These
      phytochemicals can be isolated and developed as single-ingredient drugs, with
      quality and standards of modern medicine. The major problem faced with herbal
      products is their standardization and their quality assurance. There can be batch
      to-batch variations in their efficacies as a result of natural and genetic
      alterations, seasonal changes, differences in soil and climatic conditions, and
      nutritional status of the medicinal plant. Pharmacological validation of each
      hepatoprotective plant should include efficacy evaluation against liver diseases
      induced by various agents. The most effective drugs for each kind of liver
      disease have to be selected by separate efficacy evaluations. To treat liver
      disease of known, unknown, or multiple causes, a combination of different herbs
      with active fractions (or purified compounds) has to be developed. They may prove
      to be useful in the treatment of infective, toxic, and degenerative diseases of
      the liver.

PMID- 22136108
TI  - Solution-processed organic solar cells from dye molecules: an investigation of
      diketopyrrolopyrrole:vinazene heterojunctions.
AB  - Although one of the most attractive aspects of organic solar cells is their low
      cost and ease of fabrication, the active materials incorporated into the vast
      majority of reported bulk heterojunction (BHJ) solar cells include a
      semiconducting polymer and a fullerene derivative, classes of materials which are
      both typically difficult and expensive to prepare. In this study, we demonstrate
      that effective BHJs can be fabricated from two easily synthesized dye molecules.
      Solar cells incorporating a diketopyrrolopyrrole (DPP)-based molecule as a donor
      and a dicyanoimidazole (Vinazene) acceptor function as an active layer in BHJ
      solar cells, producing relatively high open circuit voltages and power conversion
      efficiencies (PCEs) up to 1.1%. Atomic force microscope images of the films show
      that active layers are rough and apparently have large donor and acceptor domains
      on the surface, whereas photoluminescence of the blends is incompletely quenched,
      suggesting that higher PCEs might be obtained if the morphology could be improved
      to yield smaller domain sizes and a larger interfacial area between donor and
      acceptor phases.

PMID- 22136110
TI  - Advancing secondary metabolite biosynthesis in yeast with synthetic biology
      tools.
AB  - Secondary metabolites are an important source of high-value chemicals, many of
      which exhibit important pharmacological properties. These valuable natural
      products are often difficult to synthesize chemically and are commonly isolated
      through inefficient extractions from natural biological sources. As such, they
      are increasingly targeted for production by biosynthesis from engineered
      microorganisms. The budding yeast species Saccharomyces cerevisiae has proven to
      be a powerful microorganism for heterologous expression of biosynthetic pathways.
      S. cerevisiae's usefulness as a host organism is owed in large part to the wealth
      of knowledge accumulated over more than a century of intense scientific study.
      Yet many challenges are currently faced in engineering yeast strains for the
      biosynthesis of complex secondary metabolite production. However, synthetic
      biology is advancing the development of new tools for constructing, controlling,
      and optimizing complex metabolic pathways in yeast. Here, we review how the
      coupling between yeast biology and synthetic biology is advancing the use of S.
      cerevisiae as a microbial host for the construction of secondary metabolic
      pathways.

PMID- 22136109
TI  - Delayed activation of host innate immune pathways in streptozotocin-induced
      diabetic hosts leads to more severe disease during infection with Burkholderia
      pseudomallei.
AB  - Diabetes mellitus is a predisposing factor of melioidosis, contributing to higher
      mortality rates in diabetics infected with Burkholderia pseudomallei. To
      investigate how diabetes alters the inflammatory response, we established a
      streptozotocin (STZ) -induced diabetic murine acute-phase melioidosis model.
      Viable B. pseudomallei cells were consistently detected in the blood, liver and
      spleen during the 42-hr course of infection but the hyperglycaemic environment
      did not increase the bacterial burden. However, after 24 hr, granulocyte counts
      increased in response to infection, whereas blood glucose concentrations
      decreased over the course of infection. A genome-wide expression analysis of the
      STZ-diabetic murine acute melioidosis liver identified ~1000 genes whose
      expression was altered in the STZ-diabetic mice. The STZ-diabetic host
      transcriptional response was compared with the normoglycaemic host
      transcriptional response recently reported by our group. The microarray data
      suggest that the presence of elevated glucose levels impairs the host innate
      immune system by delaying the identification and recognition of B. pseudomallei
      surface structures. Consequently, the host is unable to activate the appropriate
      innate immune response over time, which may explain the increased susceptibility
      to melioidosis in the STZ-diabetic host. Nevertheless, a general 'alarm signal'
      of infection as well as defence programmes are still triggered by the STZ
      diabetic host, although only 24 hr after infection. In summary, this study
      demonstrates that in the face of a B. pseudomallei acute infection, poor
      glycaemic control impaired innate responses during the early stages of B.
      pseudomallei infection, contributing to the increased susceptibility of STZ
      induced diabetics to this fatal disease.

PMID- 22136111
TI  - Proteomics analysis of egg white proteins from different egg varieties.
AB  - The market of specialty eggs, such as omega-3-enriched eggs, organic eggs, and
      free-range eggs, is continuously growing. The nutritional composition of egg yolk
      can be manipulated by feed diet; however, it is not known if there is any
      difference in the composition of egg white proteins among different egg
      varieties. The purpose of the study was to compare the egg white proteins among
      six different egg varieties using proteomics analysis. Egg white proteins were
      analyzed using two-dimensional gel electrophoresis (2-DE), and 89 protein spots
      were subjected to LC-MS/MS. A total of 23 proteins, belonging to  Gallus gallus ,
      were identified from 72 detected protein spots. A quiescence-specific protein
      precursor in egg white was identified for the first time in this study.
      Significant differences in the abundant levels of 19 proteins (from 65 protein
      spots) were observed among six egg varieties. Four proteins, ovalbumin-related
      protein Y, cystatin, avidin, and albumin precursor, were not different among
      these six egg varieties. These findings suggest that the abundance, but not the
      composition, of egg white proteins varied among the egg varieties.

PMID- 22136112
TI  - Update of the cholesterol force field parameters in CHARMM.
AB  - A modification of the CHARMM36 lipid force field (C36) for cholesterol,
      henceforth, called C36c, is reported. A fused ring compound, decalin, was used to
      model the steroid section of cholesterol. For decalin, C36 inaccurately predicts
      the heat of vaporization (~10 kJ/mol) and molar volume (~10 cc/mol), but C36c
      resulted in near perfect comparison with experiment. MD simulations of decalin
      and heptane at various compositions were run to estimate the enthalpy and volumes
      of mixing to compare to experiment for this simple model of cholesterol in a
      chain environment. Superior estimates for these thermodynamic properties were
      obtained with C36c versus C36. These new parameters were applied to cholesterol,
      and quantum mechanical calculations were performed to modify the torsional
      potential of an acyl chain torsion for cholesterol. This model was tested through
      simulations of DMPC/10% cholesterol, DMPC/30% cholesterol, and DOPC/10%
      cholesterol. The C36 and C36c results were similar for surface areas per lipid,
      deuterium order parameters, electron density profiles, and atomic form factors
      and generally agree well with experiment. However, C36 and C36c produced slightly
      different cholesterol angle distributions with C36c adopting a more perpendicular
      orientation with respect to the bilayer plane. The new parameters in the C36c
      modification should enable more accurate simulations of lipid bilayers with
      cholesterol, especially for those interested in the free energy of lipid
      flip/flop or transfer of phospholipids and/or cholesterol.

PMID- 22136113
TI  - Neck exercises, physical and cognitive behavioural-graded activity as a treatment
      for adult whiplash patients with chronic neck pain: design of a randomised
      controlled trial.
AB  - BACKGROUND: Many patients suffer from chronic neck pain following a whiplash
      injury. A combination of cognitive, behavioural therapy with physiotherapy
      interventions has been indicated to be effective in the management of patients
      with chronic whiplash-associated disorders. The objective is to present the
      design of a randomised controlled trial (RCT) aimed at evaluating the
      effectiveness of a combined individual physical and cognitive behavioural-graded
      activity program on self-reported general physical function, in addition to neck
      function, pain, disability and quality of life in patients with chronic neck pain
      following whiplash injury compared with a matched control group measured at
      baseline and 4 and 12 months after baseline. METHODS/DESIGN: The design is a two
      centre, RCT-study with a parallel group design. Included are whiplash patients
      with chronic neck pain for more than 6 months, recruited from physiotherapy
      clinics and an out-patient hospital department in Denmark. Patients will be
      randomised to either a pain management (control) group or a combined pain
      management and training (intervention)group. The control group will receive four
      educational sessions on pain management, whereas the intervention group will
      receive the same educational sessions on pain management plus 8 individual
      training sessions for 4 months, including guidance in specific neck exercises and
      an aerobic training programme. Patients and physiotherapists are aware of the
      allocation and the treatment, while outcome assessors and data analysts are
      blinded. The primary outcome measures will be Medical Outcomes Study Short Form
      36 (SF36), Physical Component Summary (PCS). Secondary outcomes will be Global
      Perceived Effect (-5 to +5), Neck Disability Index (0-50), Patient Specific
      Functioning Scale (0-10), numeric rating scale for pain bothersomeness (0-10), SF
      36 Mental Component Summary (MCS), TAMPA scale of Kinesiophobia (17-68), Impact
      of Event Scale (0-45), EuroQol (0-1), craniocervical flexion test (22 mmHg - 30
      mmHg), joint position error test and cervical range of movement. The SF36 scales
      are scored using norm-based methods with PCS and MCS having a mean score of 50
      with a standard deviation of 10. DISCUSSION: The perspectives of this study are
      discussed, in addition to the strengths and weaknesses. TRIAL REGISTRATION: The
      study is registered in http://www.ClinicalTrials.gov identifier NCT01431261.

PMID- 22136114
TI  - Metabolic abnormalities and viral replication are associated with biomarkers of
      vascular dysfunction in HIV-infected children.
AB  - OBJECTIVES: HIV-infected children may be at risk for premature cardiovascular
      disease. We compared levels of biomarkers of vascular dysfunction in HIV-infected
      children (with and without hyperlipidaemia) with those in HIV-exposed, uninfected
      (HEU) children enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and
      determined factors associated with these biomarkers. METHODS: A prospective
      cohort study was carried out. Biomarkers of inflammation [C-reactive protein
      (CRP), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP1)],
      coagulant dysfunction (fibrinogen and P-selectin), endothelial dysfunction
      [soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell
      adhesion molecule-1 (sVCAM) and E-selectin], and metabolic dysfunction
      (adiponectin) were measured in 226 HIV-infected and 140 HEU children.
      Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity,
      and antiretroviral therapy were recorded. RESULTS: The median ages of the
      children were 12.3 years in the HIV-infected group and 10.1 years in the HEU
      group. Body mass index (BMI) z-scores, waist and hip circumferences, and
      percentage body fat were lower in the HIV-infected children. Total and non-high
      density lipoprotein (HDL) cholesterol and triglycerides were higher in HIV
      infected children. HIV-infected children also had higher MCP-1, fibrinogen, sICAM
      and sVCAM levels. In multivariable analyses in the HIV-infected children alone,
      BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and
      sVCAM. Unfavourable lipid profiles were positively associated with IL-6, MCP-1,
      fibrinogen, and P- and E-selectin, whereas increased HIV viral load was
      associated with markers of inflammation (MCP-1 and CRP) and endothelial
      dysfunction (sICAM and sVCAM). CONCLUSIONS: HIV-infected children have higher
      levels of biomarkers of vascular dysfunction than do HEU children. Risk factors
      associated with higher biomarkers include unfavourable lipid levels and active
      HIV replication.

PMID- 22136115
TI  - Automatic telangiectasia analysis in dermoscopy images using adaptive critic
      design.
AB  - BACKGROUND: Telangiectasia, tiny skin vessels, are important dermoscopy
      structures used to discriminate basal cell carcinoma (BCC) from benign skin
      lesions. This research builds off of previously developed image analysis
      techniques to identify vessels automatically to discriminate benign lesions from
      BCCs. METHODS: A biologically inspired reinforcement learning approach is
      investigated in an adaptive critic design framework to apply action-dependent
      heuristic dynamic programming (ADHDP) for discrimination based on computed
      features using different skin lesion contrast variations to promote the
      discrimination process. Lesion discrimination results for ADHDP are compared with
      multilayer perception backpropagation artificial neural networks. RESULTS: This
      study uses a data set of 498 dermoscopy skin lesion images of 263 BCCs and 226
      competitive benign images as the input sets. This data set is extended from
      previous research [Cheng et al., Skin Research and Technology, 2011, 17: 278].
      Experimental results yielded a diagnostic accuracy as high as 84.6% using the
      ADHDP approach, providing an 8.03% improvement over a standard multilayer
      perception method. CONCLUSION: We have chosen BCC detection rather than vessel
      detection as the endpoint. Although vessel detection is inherently easier, BCC
      detection has potential direct clinical applications. Small BCCs are detectable
      early by dermoscopy and potentially detectable by the automated methods described
      in this research.

PMID- 22136116
TI  - Putting the pH into phosphatidic acid signaling.
AB  - The lipid phosphatidic acid (PA) has important roles in cell signaling and
      metabolic regulation in all organisms. New evidence indicates that PA also has an
      unprecedented role as a pH biosensor, coupling changes in pH to intracellular
      signaling pathways. pH sensing is a property of the phosphomonoester headgroup of
      PA. A number of other potent signaling lipids also contain headgroups with
      phosphomonoesters, implying that pH sensing by lipids may be widespread in
      biology.

PMID- 22136117
TI  - The cost of headache disorders in Europe: the Eurolight project.
AB  - BACKGROUND AND PURPOSE: Headache disorders are very common, but their monetary
      costs in Europe are unknown. We performed the first comprehensive estimation of
      how economic resources are lost to headache in Europe. METHODS:   From November
      2008 to August 2009, a cross-sectional survey was conducted in eight countries
      representing 55% of the adult EU population. Participation rates varied between
      11% and 59%. In total, 8412 questionnaires contributed to this analysis. Using
      bottom-up methodology, we estimated direct (medications, outpatient health care,
      hospitalization and investigations) and indirect (work absenteeism and reduced
      productivity at work) annual per-person costs. Prevalence data, simultaneously
      collected and, for migraine, also derived from a systematic review, were used to
      impute national costs. RESULTS:   Mean per-person annual costs were ?1222 for
      migraine (95% CI 1055-1389; indirect costs 93%), ?303 for tension-type headache
      (TTH, 95% CI 230-376; indirect costs 92%), ?3561 for medication-overuse headache
      (MOH, 95% CI 2487-4635; indirect costs 92%), and ?253 for other headaches (95% CI
      99-407; indirect costs 82%). In the EU, the total annual cost of headache amongst
      adults aged 18-65 years was calculated, according to our prevalence estimates, at
      ?173 billion, apportioned to migraine (?111 billion; 64%), TTH (?21 billion;
      12%), MOH (?37 billion; 21%) and other headaches (?3 billion; 2%). Using the 15%
      systematic review prevalence of migraine, calculated costs were somewhat lower
      (migraine ?50 billion, all headache ?112 billion annually). CONCLUSIONS:  
      Headache disorders are prominent health-related drivers of immense economic
      losses for the EU. This has immediate implications for healthcare policy. Health
      care for headache can be both improved and cost saving.

PMID- 22136119
TI  - Language function in a child following mild traumatic brain injury: Evidence from
      pre- and post-injury language testing.
AB  - OBJECTIVE: Pre- and post-injury language performance scores following mild
      traumatic brain injury (mTBI) were investigated through a replication and
      subsequent extension of a previous case study where a trend for declining
      language scores was described based on pre- and post-injury data. METHODS: Test
      norms were used to descriptively analyze pre- and post-morbid language
      performance and performance score changes. Score changes were subsequently
      statistically analyzed using data obtained from a group of age-matched non-brain
      injured control children. RESULTS: Descriptive analysis identified a trend for
      declining skill on general and high-level language skills. Statistical analysis
      failed to differentiate the mTBI case from the control group on language score
      changes. CONCLUSIONS: While supporting the earlier identified trends in language
      decline following mTBI, subsequent statistical analysis undertaken to extend the
      earlier findings failed to detect statistically significant changes in language
      outcomes following mild injury. The need for monitoring of yet-to-emerge higher
      level adolescent language skills, however, is highlighted.

PMID- 22136118
TI  - Progenitor expansion in apc mutants is mediated by Jak/Stat signaling.
AB  - BACKGROUND: Mutations in APC, a negative regulator of the Wnt/beta-catenin
      pathway, can cause cancer as well as profound developmental defects. In both
      cases, affected cells adopt a proliferative progenitor state and fail to
      differentiate. While the upregulation of some target genes of Wnt/beta-catenin
      signaling has been shown to mediate these phenotypes in individual tissues, it is
      unclear whether a common mechanism underlies the defects in APC mutants. RESULTS:
      Here we show that stat3, a known oncogene and a target of beta-catenin in
      multiple tissues, is upregulated in apc mutant zebrafish embryos. We further
      demonstrate that Jak/Stat signaling is necessary for the increased level of
      proliferation and neural progenitor gene expression observed in apc mutants.
      CONCLUSIONS: Together, our data suggest that the regulation of Jak/Stat signaling
      may represent a conserved mechanism explaining the expansion of undifferentiated
      cells downstream of APC mutations.

PMID- 22136120
TI  - Methodological note: video analysis of the early development of Rett syndrome-
      one method for many disciplines.

PMID- 22136121
TI  - The relationship between parents' first concerns and symptoms of autism spectrum
      disorders.
AB  - OBJECTIVE: To examine the relationship between parents' first concerns and early
      Autism Spectrum Disorder (ASD) symptoms. METHODS: Symptoms of ASD were compared
      in 1393 toddlers with and without a diagnosis of an ASD, based on the area of
      parents' first concerns. Communication and behaviour problems were examined in
      the current study, as they are the most frequently reported first concerns in the
      literature. A series of one-way, between-subjects ANOVAs were conducted on each
      sub-scale of the BISCUIT Part-1. RESULTS: Symptoms of Autism Spectrum Disorders
      (ASD) significant differences were found between most groups on all sub-scales.
      On the Socialization/Non-verbal Communication and Repetitive Behaviour/Restricted
      Interest sub-scales, those with ASD and behaviour concerns had the highest
      scores. On the Communication sub-scale, those with ASD and communication concerns
      had the highest scores. CONCLUSIONS: A significant relationship exists between
      early ASD symptoms and area of first concern. The implications of these results
      are discussed.

PMID- 22136122
TI  - Training paraprofessionals to implement interventions for people autism spectrum
      disorders: a systematic review.
AB  - OBJECTIVE: This review summarizes studies in which paraprofessionals were trained
      to implement interventions for people with autism spectrum disorders (ASD) in
      school and rehabilitation settings. METHODS: Systematic searches identified 12
      studies meeting inclusion criteria. These studies were evaluated in terms of: (a)
      participant characteristics, (b) intervention implemented, (c) training
      procedures, (d) outcomes and (e) certainty of evidence. RESULTS: Across the 12
      studies intervention was provided to a total of 39 paraprofessionals including
      teacher aides and rehabilitation staff. Paraprofessionals were trained to
      implement: social stories, prompting, Picture Exchange Communication System
      (PECS), Discrete Trial Training (DTT), Pivotal Response Training (PRT),
      incidental teaching or activity schedules. Training procedures included written
      and verbal explanations, modelling, video demonstrations, role playing and
      feedback. Positive outcomes were reported in 92% of the included studies.
      CONCLUSION: Although the literature base is limited, this review highlights
      promising training procedures and areas in need of further research.

PMID- 22136123
TI  - The effects of inclusion class programmes on physical fitness for children with
      mental challenges.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of inclusion
      education programmes with special education programmes on physical fitness levels
      of children with mental challenges. METHODS: Participants were 69 elementary
      school students with mental challenges. Thirty-four children with a mean age of
      12.3 +/- 2.4 were included in an inclusion physical education programme with non
      disabled peers. In addition, 35 children with a mean age of 12.1 +/- 1.8
      participated in a special class for children with mental challenges. Balance
      tests, grip strength and Brockport Physical Fitness Test (BPFT) were used to
      evaluate the physical fitness levels of children. RESULTS: Results indicated that
      physical fitness parameters; 20 metre shuttle run, push-up, trunk lift, vertical
      jump and balance test scores were significantly lower in children in the special
      class (p < 0.05). There were no significant differences in BMI, calf skinfold
      thickness, grip strength in dominant hand, sit and reach test and modified Apley
      test (p > 0.05). CONCLUSION: The physical fitness level was better in children
      with mental challenges who were participating in an inclusion programme with non
      disabled peers. Therefore, it is recommended for children with mental challenges
      to be part of an inclusion programme with their non-disabled peers.

PMID- 22136124
TI  - Glucose and plant exudate enhanced enumeration of bacteria capable of degrading
      polycyclic aromatic hydrocarbons.
AB  - Enumerating environmental microbial isolates capable of polycyclic aromatic
      hydrocarbon (PAH) degradation can provide insight into the microbe-plant
      interactions that facilitate PAH removal. We examined a known PAH degrader (
      Pseudomonas putida  G7), a nondegrader ( Agrobacterium tumefaciens  LBA4404), and
      several microorganisms isolated from the environment by using a PAH cocktail in
      an enumeration medium with or without  0.025% (m/v) glucose and (or) root
      exudates. Compared with the standard most probable number (MPN), the addition of
      glucose and root exudates in a modified MPN method resulted in a 3- to 11-fold
      enhancement of PAH degraders being enumerated among microorganisms found in PAH
      contaminated soils. High-performance liquid chromatography analysis verified that
      PAH levels were reduced using this modified enumeration method. Low levels of
      glucose, perhaps in concert with other materials in exudates, may promote
      microbial metabolism, thereby enhancing PAH degradation.

PMID- 22136125
TI  - Application of layered poly (L-lactic acid) cell free scaffold in a rabbit
      rotator cuff defect model.
AB  - BACKGROUND: This study evaluated the application of a layered cell free poly (L
      lactic acid) (PLLA) scaffold to regenerate an infraspinatus tendon defect in a
      rabbit model. We hypothesized that PLLA scaffold without cultivated cells would
      lead to regeneration of tissue with mechanical properties similar to reattached
      infraspinatus without tendon defects. METHODS: Layered PLLA fabric with a smooth
      surface on one side and a pile-finished surface on the other side was used. Novel
      form of layered PLLA scaffold was created by superimposing 2 PLLA fabrics.
      Defects of the infraspinatus tendon were created in 32 rabbits and the PLLA
      scaffolds were transplanted, four rabbits were used as normal control.
      Contralateral infraspinatus tendons were reattached to humeral head without
      scaffold implantation. Histological and mechanical evaluations were performed at
      4, 8, and 16 weeks after operation. RESULTS: At 4 weeks postoperatively, cell
      migration was observed in the interstice of the PLLA fibers. Regenerated tissue
      was directly connected to the bone composed mainly of type III collagen, at 16
      weeks postoperatively. The ultimate failure load increased in a time-dependent
      manner and no statistical difference was seen between normal infraspinatus tendon
      and scaffold group at 8 and 16 weeks postoperatively. There were no differences
      between scaffold group and reattach group at each time of point. The stiffness
      did not improve significantly in both groups. CONCLUSIONS: A novel form of
      layered PLLA scaffold has the potential to induce cell migration into the
      scaffold and to bridge the tendon defect with mechanical properties similar to
      reattached infraspinatus tendon model.

PMID- 22136126
TI  - Improving mass transfer to soften tissues by pulsed electric fields: fundamentals
      and applications.
AB  - The mass transfer phenomenon occurs in many operations of the food industry with
      the purpose of obtaining a given substance of interest, removing water from
      foods, or introducing a given substance into the food matrix. Pretreatments that
      modify the permeability of the cell membranes, such as grinding, heating, or
      enzymatic treatment, enhance the mass transfer. However, these techniques may
      require a significant amount of energy and can cause losses of valuable food
      compounds.   Pulsed electric field (PEF) technology is a nonthermal processing
      method that causes permeabilization of cell membranes using low energy
      requirements and minimizing quality deterioration of the food compounds. Many
      practical applications of PEF for enhancing mass transfer in the food industry
      have been investigated. The purpose of this chapter is to give an overview of the
      state of the art of application of PEF for improving mass transfer in the food
      industry.

PMID- 22136127
TI  - Polymer and colloidal models describing structure-function relationships.
AB  - Colloidal and polymer systems are not only abundant in food but also useful for
      gaining insights into structure-function relationships of food. Colloid and
      polymer systems are composed of mesoscopic scale particles dispersed in a liquid.
      Because of a relatively small potential barrier against aggregation between
      mesoscopic particles, a small change in temperature, pH, or chemical compositions
      can trigger aggregation and induce remarkable changes in structure and function
      of colloidal and polymer systems. An aggregated state is not normally an
      equilibrium state but a kinetically trapped state also called a jammed state.
      Various kinetic factors in food processing, such as the rate of changes in
      temperature, water content, and chemical compositions, must be taken into account
      to establish a complete state diagram of colloid- and polymer-based food systems.

PMID- 22136128
TI  - Egg yolk antibodies for passive immunity.
AB  - The avian egg contains all of the necessary nutrients and growth factors required
      for the developing embryo, including antibodies that are transported from the
      blood of the hen into the egg yolk to provide immunity to the chick. Since the
      discovery of egg yolk antibodies, now called immunoglobulin Y (IgY), in the late
      1800s, this process has been harnessed to produce antigen-specific yolk
      antibodies for numerous applications in the medical and research fields,
      including in areas such as diagnostics and proteomics. However, one of the most
      valuable and promising areas of IgY research is its use for passive immunization
      to treat and prevent human and animal diseases. The following review covers the
      key features and advantages of IgY and the production and purification of IgY
      from the egg yolk, as well as highlights some of the most promising applications
      of egg yolk antibodies in human and veterinary medicine.

PMID- 22136129
TI  - Acrylamide in foods: a review of the science and future considerations.
AB  - Acrylamide occurs in foods commonly consumed in diets worldwide. It is formed
      from the reaction of reducing sugars (e.g., glucose or fructose) with the amino
      acid asparagine via the Maillard reaction, which occurs during heat processing of
      foods, primarily those derived from plant origin, such as potato and cereal
      products, above 120 degrees C (248 degrees F). The majority of epidemiological
      studies concerning potential relationships between acrylamide consumption and
      different types of cancer have indicated no increased risk, except with a few
      types that warrant further study. Efforts to reduce the formation of acrylamide
      in food products have resulted in some successes, but there is no common approach
      that works for all foods. Reduction in some foods is probably not possible. The
      results from a major toxicological study (aqueous intake of acrylamide by rats
      and mice) are in the process of being released. The status of current knowledge
      in these areas is reviewed.

PMID- 22136130
TI  - Mission to Mars: food production and processing for the final frontier.
AB  - The food systems of the National Aeronautics and Space Administration (NASA) have
      evolved tremendously since the early manned spaceflights of the 1960s. To date,
      NASA's mission focus has been limited to exploration of low Earth orbit (LEO),
      and the agency's prepackaged food systems have been adequate to enable success of
      their parent programs. With NASA's mission focus increasing to achieve manned
      space exploration of the Martian surface, the agency is considering a significant
      departure from the prepackaged food systems of current and past space programs.
      NASA's Advanced Food Technology (AFT) project is presently investigating the
      introduction of a bioregenerative food system to support long duration habitat
      missions to the Martian surface. A bioregenerative food system is expected to
      impart less of a burden on critical mission resources, such as mass and volume,
      than a prepackaged, shelf-stable system. This review provides an introduction to
      past and present spaceflight food systems, and provides a broad examination of
      the research conducted to date to enable crop production and food processing on
      the Martian surface.

PMID- 22136131
TI  - Maintenance of human embryonic stem cells in media conditioned by human
      mesenchymal stem cells obviates the requirement of exogenous basic fibroblast
      growth factor supplementation.
AB  - Despite the improvements in the human embryonic stem cell (hESC) culture systems,
      very similar conditions to those used to maintain hESCs on mouse feeders are
      broadly applied to culture methods based on human feeders. Indeed, basic
      fibroblast growth factor (bFGF), a master hESC-sustaining factor, is still added
      in nearly all medium formulations for hESC propagation. Human foreskin
      fibroblasts (HFFs) and mesenchymal stem cells (MSCs) used as feeders have
      recently been reported to support hESC growth without exogenous bFGF. However,
      whether hESCs may be maintained undifferentiated without exogenous bFGF using
      media conditioned (CM) by human feeders remains elusive. We hypothesize that HFFs
      and hMSCs are likely to be functionally different and therefore the mechanisms by
      which HFF-CM and MSC-CM support undifferentiated growth of hESCs may differ. We
      have thus determined whether HFF-CM and/or MSC-CM sustain feeder-free
      undifferentiated growth of hESC without exogenous supplementation of bFGF. We
      report that hMSCs synthesize higher levels of endogenous bFGF than HFFs.
      Accordingly and in contrast to HFF-CM, MSC-CM produced without the addition of
      exogenous bFGF supports hESC pluripotency and culture homeostasis beyond 20
      passages without the need of bFGF supplementation. hESCs maintained without
      exogenous bFGF in MSC-CM retained hESC morphology and expression of pluripotency
      surface markers and transcription factors, formed teratomas, and showed
      spontaneous and lineage-directed in vitro differentiation capacity. Our data
      indicate that MSC-CM, but not HFF-CM, provides microenvironment cues supporting
      feeder-free long-term maintenance of pluripotent hESCs and obviates the
      requirement of exogenous bFGF at any time.

PMID- 22136132
TI  - Controlled field evaporation of fluorinated self-assembled monolayers.
AB  - Self-assembled monolayers of amino-undecanethiol and perfluoro-decanethiol are
      studied by atom probe tomography based on laser-assisted controlled field
      desorption. In the case of hydrogenated chains the identification of detected
      molecular species is difficult because of residual hydrocarbons. By contrast,
      fractions of the fluorinated chains can be unequivocally identified. Although
      chemically similar, the evaporation of both chains appears in significantly
      different molecular fractions. For the fluorinated chains, a well-ordered
      evaporation sequence is determined that allows conclusions to be drawn about the
      strength of bonds under field conditions and may lay the basis for the future
      numerical reconstruction of the chemical structure of such films.

PMID- 22136134
TI  - Graphene oxide as a high-performance fluid-loss-control additive in water-based
      drilling fluids.
AB  - Graphene oxide (GO) performs well as a filtration additive in water-based
      drilling fluids at concentrations as low as 0.2 % (w/w) by carbon content.
      Standard American Petroleum Institute (API) filtration tests were conducted on pH
      adjusted, aqueous dispersions of GO and xanthan gum. It was found that a
      combination of large-flake GO and powdered GO in a 3:1 ratio performed best in
      the API tests, allowing an average fluid loss of 6.1 mL over 30 min and leaving a
      filter cake ~20 MUm thick. In comparison, a standard suspension (~12 g/L) of
      clays and polymers used in the oil industry gave an average fluid loss of 7.2 mL
      and a filter cake ~280 MUm thick. Scanning electron microscopy imaging revealed
      the extreme pliability of well-exfoliated GO, as the pressure due to filtration
      crumpled single GO sheets, forcing them to slide through pores with diameters
      much smaller than the flake's flattened size. GO solutions also exhibited greater
      shear thinning and higher temperature stability compared to clay-based fluid-loss
      additives, demonstrating potential for high-temperature well applications.

PMID- 22136133
TI  - Recombination hotspots and host susceptibility modulate the adaptive value of
      recombination during maize streak virus evolution.
AB  - BACKGROUND: Maize streak virus -strain A (MSV-A; Genus Mastrevirus, Family
      Geminiviridae), the maize-adapted strain of MSV that causes maize streak disease
      throughout sub-Saharan Africa, probably arose between 100 and 200 years ago via
      homologous recombination between two MSV strains adapted to wild grasses. MSV
      recombination experiments and analyses of natural MSV recombination patterns have
      revealed that this recombination event entailed the exchange of the movement
      protein - coat protein gene cassette, bounded by the two genomic regions most
      prone to recombination in mastrevirus genomes; the first surrounding the virion
      strand origin of replication, and the second around the interface between the
      coat protein gene and the short intergenic region. Therefore, aside from the
      likely adaptive advantages presented by a modular exchange of this cassette,
      these specific breakpoints may have been largely predetermined by the underlying
      mechanisms of mastrevirus recombination. To investigate this hypothesis, we
      constructed artificial, low-fitness, reciprocal chimaeric MSV genomes using
      alternating genomic segments from two MSV strains; a grass-adapted MSV-B, and a
      maize-adapted MSV-A. Between them, each pair of reciprocal chimaeric genomes
      represented all of the genetic material required to reconstruct - via
      recombination - the highly maize-adapted MSV-A genotype, MSV-MatA. We then co
      infected a selection of differentially MSV-resistant maize genotypes with pairs
      of reciprocal chimaeras to determine the efficiency with which recombination
      would give rise to high-fitness progeny genomes resembling MSV-MatA. RESULTS:
      Recombinants resembling MSV-MatA invariably arose in all of our experiments.
      However, the accuracy and efficiency with which the MSV-MatA genotype was
      recovered across all replicates of each experiment depended on the MSV
      susceptibility of the maize genotypes used and the precise positions - in
      relation to known recombination hotspots - of the breakpoints required to re
      create MSV-MatA. Although the MSV-sensitive maize genotype gave rise to the
      greatest variety of recombinants, the measured fitness of each of these
      recombinants correlated with their similarity to MSV-MatA. CONCLUSIONS: The
      mechanistic predispositions of different MSV genomic regions to recombination can
      strongly influence the accessibility of high-fitness MSV recombinants. The
      frequency with which the fittest recombinant MSV genomes arise also correlates
      directly with the escalating selection pressures imposed by increasingly MSV
      resistant maize hosts.

PMID- 22136135
TI  - Neuropeptide Y inhibits interleukin-1beta-induced phagocytosis by microglial
      cells.
AB  - BACKGROUND: Neuropeptide Y (NPY) is emerging as a modulator of communication
      between the brain and the immune system. However, in spite of increasing evidence
      that supports a role for NPY in the modulation of microglial cell responses to
      inflammatory conditions, there is no consistent information regarding the action
      of NPY on microglial phagocytic activity, a vital component of the inflammatory
      response in brain injury. Taking this into consideration, we sought to assess a
      potential new role for NPY as a modulator of phagocytosis by microglial cells.
      METHODS: The N9 murine microglial cell line was used to evaluate the role of NPY
      in phagocytosis. For that purpose, an IgG-opsonized latex bead assay was
      performed in the presence of lipopolysaccharide (LPS) and an interleukin-1beta
      (IL-1beta) challenge, and upon NPY treatment. A pharmacological approach using
      NPY receptor agonists and antagonists followed to uncover which NPY receptor was
      involved. Moreover, western blotting and immunocytochemical studies were
      performed to evaluate expression of p38 mitogen-activated protein kinase (MAPK)
      and heat shock protein 27 (HSP27), in an inflammatory context, upon NPY
      treatment. RESULTS: Here, we show that NPY inhibits phagocytosis of opsonized
      latex beads and inhibits actin cytoskeleton reorganization triggered by LPS
      stimulation. Co-stimulation of microglia with LPS and adenosine triphosphate also
      resulted in increased phagocytosis, an effect inhibited by an interleukin-1
      receptor antagonist, suggesting involvement of IL-1beta signaling. Furthermore,
      direct application of LPS or IL-1beta activated downstream signaling molecules,
      including p38 MAPK and HSP27, and these effects were inhibited by NPY. Moreover,
      we also observed that the inhibitory effect of NPY on phagocytosis was mediated
      via Y1 receptor activation. CONCLUSIONS: Altogether, we have identified a novel
      role for NPY in the regulation of microglial phagocytic properties, in an
      inflammatory context.

PMID- 22136136
TI  - Utilization of chicken feather hydrolysate as a novel fermentation substrate for
      production of exopolysaccharide and mycelial biomass from edible mushroom
      Morchella esculenta.
AB  - This study was performed to investigate the usability of chicken feather
      hydrolysate (Chicken feather peptone (CFP)) as substrate for mycelial biomass and
      extracellular polysaccharides (EPS) production from edible mushroom Morchella
      esculenta. The ability of CFP to support biomass and EPS production in edible
      mushroom M. esculenta was compared to those of two commercial peptones (Tryptone
      peptone (TP) and Fish peptone (FP)). The maximum biomass (16.3 g/l) and EPS (4.8
      g/l) concentrations were achieved with TP. Second, high biomass (15.9 g/l) and
      EPS (4.6 g/l) concentrations were obtained with CFP. Also, biomass and EPS
      concentrations in CFP medium were statistically near to those in the TP medium.
      CFP and TP resulted in not only uniform pellets with smaller size (5 mm) but also
      faster mycelial growth compared to FP. This study showed for the first time that
      CFP could be effectively used as a novel EPS production substrate.

PMID- 22136137
TI  - Sb(III) and Sb(V) sorption onto Al-rich phases: hydrous Al oxide and the clay
      minerals kaolinite KGa-1b and oxidized and reduced nontronite NAu-1.
AB  - We have studied the immobilization of Sb(III) and Sb(V) by Al-rich phases -
      hydrous Al oxide (HAO), kaolinite (KGa-1b), and oxidized and reduced nontronite
      (NAu-1) - using batch experiments to determine the uptake capacity and the
      kinetics of adsorption and Extended X-ray Absorption Fine Structure (EXAFS)
      Spectroscopy to characterize the molecular environment of adsorbed Sb. Both
      Sb(III) and Sb(V) are adsorbed in an inner-sphere mode on the surfaces of the
      studied substrates. The observed adsorption geometry is mostly bidentate corner
      sharing, with some monodentate complexes. The kinetics of adsorption is
      relatively slow (on the order of days), and equilibrium adsorption isotherms are
      best fit using the Freundlich model. The oxidation state of the structural Fe
      within nontronite affects the adsorption capacity: if the clay is reduced, the
      adsorption capacity of Sb(III) is slightly decreased, while Sb(V) uptake is
      increased significantly. This may be a result of the presence of dissolved Fe(II)
      in the reduced nontronite suspensions or associated with the structural
      rearrangements in nontronite due to reduction. These research findings indicate
      that Sb can be effectively immobilized by Al-rich phases. The increase in Sb(V)
      uptake in response to reducing structural Fe in clay can be important in natural
      settings since Fe-rich clays commonly go through oxidation-reduction cycles in
      response to changing redox conditions.

PMID- 22136138
TI  - One-year survival of demented stroke patients: data from the Dijon Stroke
      Registry, France (1985-2008).
AB  - BACKGROUND AND PURPOSE:   Dementia is a frequent condition after stroke that may
      affect the prognosis of patients. Our aim was to determine whether post-stroke
      dementia was a predictor of 1-year case-fatality and to evaluate factors that
      could influence survival in demented stroke patients. METHODS: From 1985 to 2008,
      all first-ever strokes were recorded in the population-based stroke registry of
      Dijon, France (150, 000 inhabitants). Dementia was diagnosed during the first
      month following stroke, according to DSM-III and DSM-IV criteria. Survival was
      evaluated at 1 year and multivariate analyses were performed using Cox
      proportional hazards to identify independent predictive factors. RESULTS:   We
      recorded 3948 first-ever strokes. Among these stroke patients, 3201 (81%) were
      testable, and of these, 653 (20.4%) had post-stroke dementia (337 women and 316
      men). Demented patients had lower 1-year survival than patients without dementia
      (82.9% vs. 86.9%, P = 0.013). However, in multivariate analysis, dementia did not
      appear as an independent predictor of 1-year death. In demented stroke patients,
      age >80 years old, severe handicap at discharge, recurrent stroke within the
      first year and subarachnoid haemorrhage were associated with a higher risk of 1
      year death, and the risk was lower in the study period 2003-2008. CONCLUSIONS:  
      Dementia after stroke is not independently associated with an increased risk of
      death at 1 year. In recent years, 1-year case-fatality decreased in demented as
      well as in and non-demented patients suggesting that improvements in the
      management of stroke also benefited the most fragile patients.

PMID- 22136139
TI  - Evolutionary engineering of Saccharomyces cerevisiae for improved industrially
      important properties.
AB  - This article reviews evolutionary engineering of Saccharomyces cerevisiae.
      Following a brief introduction to the 'rational' metabolic engineering approach
      and its limitations such as extensive genetic and metabolic information
      requirement on the organism of interest, complexity of cellular physiological
      responses, and difficulties of cloning in industrial strains, evolutionary
      engineering is discussed as an alternative, inverse metabolic engineering
      strategy. Major evolutionary engineering applications with S. cerevisiae are then
      discussed in two general categories: (1) evolutionary engineering of substrate
      utilization and product formation and (2) evolutionary engineering of stress
      resistance. Recent developments in functional genomics methods allow rapid
      identification of the molecular basis of the desired phenotypes obtained by
      evolutionary engineering. To conclude, when used alone or in combination with
      rational metabolic engineering and/or computational methods to study and analyze
      processes of adaptive evolution, evolutionary engineering is a powerful strategy
      for improvement in industrially important, complex properties of S. cerevisiae.

PMID- 22136140
TI  - Synthesis, structure, and reactivity of carbene-stabilized phosphorus(III)
      centered trications [L3P]3+.
AB  - Carbene-stabilized [L(3)P](+3) cations have been synthesized for the first time
      by a reaction between 1-chloro-2,3-bis(dialkylamino)cyclopropenium salts and
      P(SiMe(3))(3). In addition, the first structural characterization of such an
      entity is reported. Consistent with the X-ray data, density functional
      calculations indicate that these P-centered cations, despite their high positive
      charge, still feature a nonbonding electron pair on the P-atom (HOMO) and a very
      low-lying LUMO depicting them as poor sigma-donors and excellent pi-acceptors.

PMID- 22136141
TI  - Influence of preoperative nucleus pulposus status and radiculopathy on outcomes
      in mono-segmental lumbar total disc replacement: results from a nationwide
      registry.
AB  - BACKGROUND: Currently, herniated nucleus pulposus (HNP) with radiculopathy and
      other preconditions are regarded as relative or absolute contraindications for
      lumbar total disc replacement (TDR). In Switzerland it is left to the surgeon's
      discretion when to operate. The present study is based on the dataset of
      SWISSspine, a governmentally mandated health technology assessment registry. We
      hypothesized that preoperative nucleus pulposus status and presence or absence of
      radiculopathy has an influence on clinical outcomes in patients treated with mono
      segmental lumbar TDR. METHODS: Between March 2005 and April 2009, 416 patients
      underwent mono-segmental lumbar TDR, which was documented in a prospective
      observational multicenter mode. The data collection consisted of perioperative
      and follow-up data (physician based) and clinical outcomes (NASS, EQ-5D).Patients
      were divided into four groups according to their preoperative status: 1) group
      degenerative disc disease ("DDD"): 160 patients without HNP and no radiculopathy,
      classic precondition for TDR; 2) group "HNP-No radiculopathy": 68 patients with
      HNP but without radiculopathy; 3) group "Stenosis": 73 patients without HNP but
      with radiculopathy, and 4) group "HNP-Radiculopathy": 132 patients with HNP and
      radiculopathy. The groups were compared regarding preoperative patient
      characteristics and pre- and postoperative VAS and EQ-5D scores using general
      linear modeling. RESULTS: Demographics in all four groups were comparable.
      Regarding the improvement of quality of life (EQ-5D) there were no differences
      across the four groups. For the two main groups DDD and HNP-Radiculopathy no
      differences were found in the adjusted postoperative back- and leg pain
      alleviation levels, in the stenosis group back- and leg pain relief were lower.
      CONCLUSIONS: Despite higher preoperative leg pain levels, outcomes in lumbar TDR
      patients with HNP and radiculopathy were similar to outcomes in patients with the
      classic indication; this because patients with higher preoperative leg pain
      levels benefit from a relatively greater leg pain alleviation. The group with
      absence of HNP but presence of radiculopathy showed considerably less benefits
      from the operation, which is probably related to ongoing degenerative processes
      of the posterior segmental structures. This observational multicenter study
      suggests that the diagnoses HNP and radiculopathy, combined or alone, may not
      have to be considered as absolute or relative contraindications for mono
      segmental lumbar TDR anymore, whereas patients without HNP but with radiculopathy
      seem to be suboptimal candidates for the procedure.

PMID- 22136142
TI  - Depletion of complement does not impact initiation of xenobiotic-induced
      autoimmune disease.
AB  - Deficiency in Daf1, a complement regulatory protein, has been shown to exacerbate
      development of various autoimmune diseases and recent studies have suggested that
      this may be explained by Daf1 acting to limit T-cell hyper-responsiveness. It has
      been suggested that the absence of Daf1 aggravates autoimmune disease in a
      complement-dependent manner, but others have shown that activation of T cells in
      the absence of Daf1 can be complement independent. However, the relationship
      between Daf1, complement components, lymphocyte activation, cytokine expression
      and antibody production remains to be determined in mice that are not Daf1
      deficient. We have recently demonstrated, in murine mercury-induced autoimmunity
      (mHgIA), that an accumulation of CD44(high) Daf(low) CD4(+) T cells is associated
      with the development of autoimmunity. In this study we observed that complement
      depletion does not affect the accumulation of activated CD4(+) T cells, elevation
      of splenic interleukin-4 expression and autoantibody production in mHgIA. In
      addition, neither the accumulation of CD44(high) Daf(low) CD4(+) T cells nor the
      down-regulation of Daf1 expression on CD4(+) T cells was influenced by a lack of
      complement. In conclusion, these studies show that initiating events in
      xenobiotic-induced autoimmunity, including lymphocyte activation, cytokine
      expression and autoantibody production, are not dependent on complement.

PMID- 22136143
TI  - Impact of extra virgin olive oil and ethylenediaminetetraacetic acid (EDTA) on
      the oxidative stability of fish oil emulsions and spray-dried microcapsules
      stabilized by sugar beet pectin.
AB  - The influence of EDTA on lipid oxidation in sugar beet pectin-stabilized oil-in
      water emulsions (pH 6, 15% oil, wet basis), prepared from fish oil (FO) and fish
      oil-extra virgin olive oil (FO-EVOO) (1:1 w/w), as well as the spray-dried
      microcapsules (50% oil, dry basis) prepared from these emulsions, was
      investigated. Under accelerated conditions (80  degrees C, 5 bar oxygen pressure)
      the oxidative stability was significantly (P < 0.05) higher for FO and FO-EVOO
      formulated with EDTA, in comparison to corresponding emulsions and spray-dried
      microcapsules formulated without EDTA. The EDTA effect was greater in emulsions
      than in spray-dried microcapsules, with the greatest protective effect obtained
      in FO-EVOO emulsions. EDTA enhanced the oxidative stability of the spray-dried
      microcapsules during ambient storage (~25  degrees C, a(w) = 0.5), as
      demonstrated by their lower concentration of headspace volatile oxidation
      products, propanal and hexanal. These results show that the addition of EDTA is
      an effective strategy to maximize the oxidative stability of both FO emulsions
      and spray-dried microcapsules in which sugar beet pectin is used as the
      encapsulant material.

PMID- 22136144
TI  - Gender-specific differences in susceptibility to low-dose methadone-associated
      QTc prolongation in patients with heroin dependence.
AB  - BACKGROUND: Methadone is associated with QTc prolongation and sudden death in
      susceptible patients. We sought to investigate whether there is a gender-based
      difference in susceptibility to methadone-associated QTc prolongation in heroin
      dependent patients receiving a low-dose treatment regimen. METHODS: A cross
      sectional assessment of dose and gender effects was performed in 283 patients
      (229 males, 54 females) who received a 12-lead ECG for QTc measurement 59 days
      (interquartile range: 36-288 days) after methadone treatment. To determine the
      effects of methadone over time, a subset of 150 participants (126 men, 24 women)
      who underwent a 12-lead ECG before and 37 days (interquartile range: 32-44 days)
      after methadone treatment were selected. RESULTS: In the cross-sectional study, a
      significant dose-dependent interaction between methadone and QTc (r = 0.201, P =
      0.0007) was observed in individuals receiving a median methadone dose of 40
      mg/day (interquartile range: 30-60 mg/day). The methadone-QTc correlation was
      significant in males (r = 0.210, P = 0.0014) but not in females (r = 0.164, P =
      0.2363). The longitudinal assessment of methadone's effects over a 6-month period
      showed that 60.7% of individuals experienced an increase in QTc compared to
      baseline data. The adjusted QTc significantly increased from 418.5 to 426.9
      milliseconds in males (P < 0.0001), compared to an insignificant change in
      females (437.7 milliseconds vs 441.1 milliseconds, P = 0.468). CONCLUSIONS: Low
      dose methadone therapy shows dose-dependent QTc prolongation and is associated
      with significant QTc lengthening within 6 months of treatment initiation. Men are
      more susceptible than women to low-dose methadone-associated QTc prolongation.

PMID- 22136145
TI  - The importance of side difference in nasal obstruction and rhinomanometry: a
      retrospective correlation of symptoms and rhinomanometry in 1000 patients.
AB  - OBJECTIVES: The correlation between subjective and objective outcomes of nasal
      obstruction is still a matter of controversy. The aim of this study was to
      determine the minimal level of side difference in nasal airway resistance (NAR
      measured by Broms'v(2)) between the two nasal cavities, which could be discerned
      subjectively by the patient on a visual analogue scale (VAS). Nasal airway
      resistance was calculated from rhinomanometric measurements of nasal airflow and
      transnasal pressure after decongestion of the nasal mucosa. DESIGN: A
      retrospective study. SETTING: ENT department, Vaxjo Central Hospital, Sweden.
      PARTICIPANTS: We studied 1000 active anterior rhinomanometries from patients with
      nasal obstructions. MAIN OUTCOME MEASURES: We compared the side difference of
      nasal airway resistance with the side difference of VAS estimated immediately
      prior to the rhinomanometry. Each measurement was performed after nasal
      decongestion. RESULTS: When the difference in nasal airway resistance between the
      two nasal cavities was larger than 20 degrees  (Broms'v(2)) or R(2) > 0.36
      Pa/cm(3) /s, we found a significant correlation between side differences of the
      objective measurement and the subjective assessment (VAS). With a nasal airway
      resistance side difference over 20 degrees , an additional 20 degrees  difference
      corresponded to a 0.9 centimetre average VAS change. The more obstructed side of
      the nose could be determined by VAS in 823 (82.3%) of 1000 patients. Yet, 177
      (17.7%) patients had a paradoxical sensation of nasal obstruction with the low
      resistance side of the nose experienced as the most congested side. CONCLUSION: A
      significant correlation between the side differences of nasal airway resistance
      and VAS can serve as a supplement to rhinoscopy in decisions about nasal surgery.
      This study also showed that in 17.7% of patients, there was a negative
      correlation between subjective and objective evaluations of nasal airway
      resistance. But in this group, the nasal airway resistance side difference was
      mostly under 20 degrees .

PMID- 22136146
TI  - Visual function in patients on ethambutol therapy for tuberculosis.
AB  - PURPOSE: Aim of the study was to evaluate the effects of ethambutol therapy in
      visual functions. METHODS: Prospective evaluation of 88 eyes of 44 patients on
      ethambutol therapy under Directly Observed Treatment Short-course (category I)
      for primary tuberculosis was done before start of ethambutol therapy and after 2
      months of starting the therapy. Parameters evaluated were visual acuity with
      Bailey Lovie Log-MAR chart, contrast sensitivity with Pelli-Robson contrast
      sensitivity chart, color vision with Farnsworth D15 test, visual fields with
      Octopus automated perimetry, and multifocal electroretinography (ERG) with Roland
      RETI scan along with anterior and posterior segments evaluation. RESULTS: No
      visual functional defect was noted at baseline. On follow-up, color vision,
      visual field parameters, and anterior and posterior segment findings were not
      affected in any patients. Mean visual acuity before starting therapy was 0.00+/
      0.08 Log-MAR and after therapy was 0.08+/-0.18 Log-MAR. Change in visual acuity
      was statistically significant (p=0.004). Difference between contrast sensitivity
      before and after therapy was statistically highly significant both monocularly
      and binocularly (p<0.005 in both cases). P1 amplitudes (in terms of nV/deg(2) and
      MUV) of ERG waves were significantly reduced and their P1 latencies were
      significantly increased in all the rings after ethambutol therapy (p<0.05). There
      was no significant change in N1 amplitudes and N1 latencies after therapy in any
      of the rings. CONCLUSIONS: Visual acuity, contrast sensitivity, and multifocal
      ERG are sensitive tests to detect ethambutol toxicity in subclinical stages and
      hence very useful tools for monitoring patients under ethambutol therapy for
      ocular toxicity.

PMID- 22136147
TI  - Inhibitory potential of traditional herbs on alpha-amylase activity.
AB  - CONTEXT: There has been enormous interest in the development of alternative
      medicines for the control of diabetes. Use of carbohydrate-hydrolyzing enzyme
      inhibitors proved to be an important strategy for the management of postprandial
      hyperglycemia by delaying the process of carbohydrate hydrolysis and absorption.
      OBJECTIVE: Three common traditional herbs, namely, stem bark of Terminalia arjuna
      (Combretaceae), seeds of Eugenia cumini (Myrtaceae), and leaves of Aegle marmelos
      (Rutaceae), were tested for their alpha-amylase inhibitory activities to
      establish antidiabetic potential. MATERIALS AND METHODS: The plant extracts
      (aqueous, 50%, and 100% methanol) obtained were subjected to an in vitro amylase
      inhibitory assay using starch as a substrate and pancreatic amylase as the
      enzyme. Statistical differences and linear regression analysis were performed
      using GraphPad prism 5 software. RESULTS: The 50% methanol extracts of T. arjuna,
      E. cumini, and A. marmelos at a concentrations 50-500 MUg/mL showed maximum
      percentage inhibition on amylase activity with IC(50) values of 302 +/- 0.55, 632
      +/- 0.21, and 503 +/- 0.28 MUg/mL, respectively. However, the 100% methanol
      extracts of all the three plants showed the least inhibitory activity. DISCUSSION
      AND CONCLUSION: The results show that T. arjuna > E. cumini > A. marmelos have
      excellent inhibitory activity and, therefore, might be effective in lowering
      postprandial hyperglycemia.

PMID- 22136148
TI  - Hyperosmolar glucose induces vasoconstriction through Rho/Rho-kinase pathway in
      the rat aorta.
AB  - Rho/Rho-kinase signalling pathway plays a substantial role in vascular
      contractions. In this study, we investigated any roles of Rho/Rho-kinase pathway
      in the vasoconstriction of the rat conductance and capacitance vessels by
      hyperosmolar glucose solution. Isolated aortic, mesenteric and renal rings were
      suspended and exposed to hyperosmolar glucose, sucrose and NaCl in the organ
      chambers filled with Krebs solution gassed with 95% O2 and 5% CO2 and maintained
      at 37  degrees C. The effect of a Rho-kinase inhibitor, (+)-(R)-trans-4-(1
      aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y
      27632, 10(-5) M), was tested on the contraction induced by hypertonic solutions.
      Endothelial integrity was also assessed after hyperosmolar glucose exposure.
      Moreover, the activity and expression of Rho-kinase (ROCK-2) as well as RhoA
      translocation were detected by Western blotting and enzyme-linked immunosorbent
      assay-based RhoA activity detection method detection kit. The vessels produced
      substantial contractions in response to hyperosmolar solutions. Y-27632
      significantly reduced hyperosmolarity-induced vasoconstrictions (P < 0.05).
      Phosphorylation of myosin-phosphatase target 1 increased after hyperosmolar
      glucose exposure, and this phosphorylation was significantly decreased by Y-27632
      (P < 0.05) in the aorta. Furthermore, RhoA translocation but not ROCK-2
      expression markedly increased by hyperosmolar glucose solution. These results may
      indicate that hyperosmolarity could induce vasoconstriction through Rho/Rho
      kinase signalling.

PMID- 22136149
TI  - Efficacy and safety of ketamine in patients with complex regional pain syndrome:
      a systematic review.
AB  - Despite being a recognized clinical entity for over 140 years, complex regional
      pain syndrome (CRPS) remains a difficult-to-treat condition. While there have
      been multiple therapies explored in the treatment of CRPS, NMDA antagonists such
      as ketamine continue to hold significant interest because of their potential
      ability to alter the central sensitization noted in chronic pain states. The
      objective of this review is to identify published literature for evidence of the
      efficacy and safety of ketamine in the treatment of CRPS. PubMed and the Cochrane
      Controlled Trials Register were searched (final search 26 May 2011) using the
      MeSH terms 'ketamine', 'complex regional pain syndrome', 'analgesia' and 'pain'
      in the English literature. The manuscript bibliographies were then reviewed to
      identify additional relevant papers. Observational trials were evaluated using
      the Agency for Healthcare Research and Quality criteria; randomized trials were
      evaluated using the methodological assessment of randomized clinical trials. The
      search methodology yielded three randomized, placebo-controlled trials, seven
      observational studies and nine case studies/reports. In aggregate, the data
      available reveal ketamine as a promising treatment for CRPS. The optimum dose,
      route and timing of administration remain to be determined. Randomized controlled
      trials are needed to establish the efficacy and safety of ketamine and to
      determine its long-term benefit in CRPS.

PMID- 22136150
TI  - Pharmacological interventions for the treatment of smokeless tobacco use.
AB  - Smokeless tobacco (SLT) is used in a variety of forms throughout the world. Long
      term SLT use is associated with adverse health consequences. Effective
      pharmacotherapies are needed to treat SLT users who want to achieve tobacco
      abstinence. In the current review, we discuss the pharmacological interventions
      identified in a recent meta-analysis of interventions for SLT users, with
      inclusion of additional articles identified by searching PubMed up to August
      2011. Nicotine replacement therapy (NRT) has been demonstrated to increase short
      term tobacco abstinence rates and to alleviate craving and withdrawal symptoms
      among SLT users trying to quit. Bupropion sustained release has been shown to
      decrease craving and attenuate post-cessation weight gain among SLT users trying
      to quit. Varenicline is the only available medication demonstrated to increase
      long-term (>=6 months) tobacco abstinence rates among SLT users. Overall,
      findings from studies investigating pharmacotherapies for SLT users have been
      relatively disappointing. SLT reduction interventions may hold some promise for
      increasing abstinence rates among SLT users not interested in quitting.
      Additional investigations of higher dose NRT and combination pharmacotherapy are
      needed to advance the treatment of SLT users.

PMID- 22136151
TI  - On-chip transduction of nucleic acid hybridization using spatial profiles of
      immobilized quantum dots and fluorescence resonance energy transfer.
AB  - The glass surface of a glass-polydimethylsiloxane (PDMS) microfluidic channel was
      modified to develop a solid-phase assay for quantitative determination of nucleic
      acids. Electroosmotic flow (EOF) within channels was used to deliver and
      immobilize semiconductor quantum dots (QDs), and electrophoresis was used to
      decorate the QDs with oligonucleotide probe sequences. These processes took only
      minutes to complete. The QDs served as energy donors in fluorescence resonance
      energy transfer (FRET) for transduction of nucleic acid hybridization.
      Electrokinetic injection of fluorescent dye (Cy3) labeled oligonucleotide target
      into a microfluidic channel and subsequent hybridization (within minutes)
      provided the proximity for FRET, with emission from Cy3 being the analytical
      signal. The quantification of target concentration was achieved by measurement of
      the spatial length of coverage by target along a channel. Detection of femtomole
      quantities of target was possible with a dynamic range spanning an order of
      magnitude. The assay provided excellent resistance to nonspecific interactions of
      DNA. Further selectivity of the assay was achieved using 20% formamide, which
      allowed discrimination between a fully complementary target and a 3 base pair
      mismatch target at a contrast ratio of 4:1.

PMID- 22136153
TI  - Increased arterial stiffness in mildly-hypertensive women with polycystic ovary
      syndrome.

PMID- 22136152
TI  - Molecular imaging in Alzheimer's disease: new perspectives on biomarkers for
      early diagnosis and drug development.
AB  - Recent progress in molecular imaging has provided new important knowledge for
      further understanding the time course of early pathological disease processes in
      Alzheimer's disease (AD). Positron emission tomography (PET) amyloid beta (Abeta)
      tracers such as Pittsburgh Compound B detect increasing deposition of fibrillar
      Abeta in the brain at the prodromal stages of AD, while the levels of fibrillar
      Abeta appear more stable at high levels in clinical AD. There is a need for PET
      ligands to visualize smaller forms of Abeta, oligomeric forms, in the brain and
      to understand how they interact with synaptic activity and neurodegeneration. The
      inflammatory markers presently under development might provide further insight
      into the disease mechanism as well as imaging tracers for tau. Biomarkers
      measuring functional changes in the brain such as regional cerebral glucose
      metabolism and neurotransmitter activity seem to strongly correlate with clinical
      symptoms of cognitive decline. Molecular imaging biomarkers will have a clinical
      implication in AD not only for early detection of AD but for selecting patients
      for certain drug therapies and to test disease-modifying drugs. PET fibrillar
      Abeta imaging together with cerebrospinal fluid biomarkers are promising as
      biomarkers for early recognition of subjects at risk for AD, for identifying
      patients for certain therapy and for quantifying anti-amyloid effects. Functional
      biomarkers such as regional cerebral glucose metabolism together with measurement
      of the brain volumes provide valuable information about disease progression and
      outcome of drug treatment.

PMID- 22136154
TI  - Diphenylparabanic acid as a synthon for the synthesis of alpha-diketones and
      alpha-ketocarboxylic acids.
AB  - Diphenylparabanic acid was found to react with >2 equiv of organolithiums at -78 
      degrees C to effectively give the corresponding symmetrical alpha-diketones.
      However, upon treatment with 1 equiv of organolithium, the parabanic acid gave
      mainly 5-substituted 5-hydroxyimidazolidine-2,4-diones. On the other hand,
      Grignard reagents were less reactive toward the parabanic acid at low
      temperature, and selectively gave the corresponding 5-hydroxyimidazolidine-2,4
      diones even if more than 1 equiv of the reagents was used. A tandem process in
      which the parabanic acid was first reacted with a Grignard reagent and then
      reacted in one-pot with an organolithium effectively gave the unsymmetrical alpha
      diketone. 5-Substituted 5-hydroxyimidazolidine-2,4-diones were useful as
      versatile precursors for preparing alpha-ketocarboxylic acids as well as
      unsymmetrical alpha-diketones.

PMID- 22136155
TI  - Isolation and molecular characterization of  Chikungunya virus  from the Andaman
      and Nicobar archipelago, India: evidence of an East, Central, and South African
      genotype.
AB  - Chikungunya virus (CHIKV) is an Alphavirus belonging to the family Togaviridae.
      In 2006, CHIKV infection struck the Andaman and Nicobar archipelago, with an
      attack rate of 60%. There were more than 10 cases with acute flaccid paralysis
      simulating the Guillian Barre Syndrome. The majority of the patients presented
      severe joint pain. The cause for such an explosive nature of the outbreak with
      increased morbidity was not known. The isolation of CHIKV was attempted and
      succeeded from nine subjects presenting clinical symptoms of Chikungunya fever.
      The cDNA of all the isolates was sequenced for partial E1 and nsP1 genes.
      Sequences were aligned based on the double locus sequence typing concept. The
      phylogenetic analysis shows that sequences of Andaman isolates grouped with the
      East, Central, and South African genotype of virus isolates from India, Sri
      Lanka, and Reunion. The genetic distance between Andaman isolates and the Reunion
      isolates was very small. The phylogenetic analysis confirmed the origin of the
      isolates responsible for the first ever confirmed CHIKV outbreak in these islands
      to be the East, Central, and South African genotype. In this manuscript, we
      discuss the involvement of the East, Central, and South African strain with the
      Chikungunya fever outbreak in this archipelago and double locus sequence typing
      as a first time approach.

PMID- 22136156
TI  - T3 rapidly increases SLC2A4 gene expression and GLUT4 trafficking to the plasma
      membrane in skeletal muscle of rat and improves glucose homeostasis.
AB  - BACKGROUND: Glucose transporter 4 (GLUT4) is highly expressed in muscle and fat
      tissue, where triiodothyronine (T(3)) induces solute carrier family 2 facilitated
      glucose transporter member 4 (SLC2A4) gene transcription. T(3) was also shown to
      rapidly increase glucose uptake in myocytes exposed to cycloheximide, indicating
      that it might act nongenomically to regulate GLUT4 availability. We tested this
      hypothesis by evaluating, in thyroidectomized rats (Tx rats), the acute and/or
      chronic T(3) effects on GLUT4 mRNA expression and polyadenylation, protein
      content, and trafficking to the plasma membrane (PM) in skeletal muscle, as well
      as on blood glucose disappearance rate (kITT) after insulin administration.
      METHODS: Rats were surgically thyroidectomized and treated with T(3) (0.3 to 100
      MUg/100 g body weight) from 10 minutes to 5 days, and killed thereafter. Sham
      operated (SO) rats were used as controls. Total RNA was extracted from the
      skeletal muscles (soleus [SOL] and extensorum digitalis longus [EDL]) and
      subjected to Northern blotting analysis using rat GLUT4 cDNA probe. Total protein
      was extracted and subjected to specific centrifugations for subcellular
      fractionation, and PM as well as microsomal (M) fractions were subjected to
      Western blotting analysis, using anti-GLUT4 antiserum as a probe. GLUT4 mRNA
      polyadenylation was examined by a rapid amplification of cDNA ends-poly(A) test
      (RACE-PAT). RESULTS: Thyroidectomy reduced skeletal muscle GLUT4 mRNA, mRNA
      poly(A) tail length, protein content, and trafficking to the PM, as well as the
      kITT. The acute T(3) treatment rapidly (30 minutes) increased all these
      parameters compared with Tx rats. The 5-day T(3) treatment increased GLUT4 mRNA
      and protein expression, and restored GLUT4 trafficking to the PM and kITT to SO
      values. CONCLUSIONS: The results presented here show for the first time that, in
      parallel to its transcriptional action on the SLC2A4 gene, T(3) exerts a rapid
      post-transcriptional effect on GLUT4 mRNA polyadenylation, which might increase
      transcript stability and translation efficiency, leading to the increased GLUT4
      content and availability to skeletal muscle, as well as on GLUT4 translocation to
      the PM, improving the insulin sensitivity, as shown by the kITT.

PMID- 22136157
TI  - Thyroid cancer patients treated with 131I: radiation dose to relatives after
      discharge from the hospital.
AB  - BACKGROUND: Thyroid cancer patients treated with radioiodine are potential source
      of radiation exposure for other individuals. Thus, we evaluated the radiation
      dose received by family members of thyroid cancer patients treated with (131)I
      after hospital discharge. MATERIALS AND METHODS: Seventy-six family members of 56
      thyroid cancer patients were included in the study. Thyroid cancer patients were
      given 3.7 GBq of (131)I and remained in a radiation protection ward for 3 days.
      Radiation protection recommendations were given to patients and relatives. Life
      conditions were recorded and radiation doses were monitored using a personal
      dosimeter. RESULTS AND DISCUSSION: At discharge, the mean residual activity was
      188 MBq. The mean radiation dose delivered to relatives during the 7 days after
      discharge was low (51.5 MUSv) and was similar with either recombinant human
      thyrotropin (rhTSH) (59 MUSv) or withdrawal (50 MUSv) (p = 0.37). CONCLUSION:
      With our current practice, radiation doses to relatives are low and well below
      international recommendations.

PMID- 22136158
TI  - Assessing the role of spatial engagement and disengagement of attention in
      anxiety-linked attentional bias: a critique of current paradigms and suggestions
      for future research directions.
AB  - A considerable volume of research has demonstrated an anxiety-linked attentional
      bias characterized by selective processing of threat stimuli. The last decade has
      seen growing interest in identifying the precise attentional mechanisms which
      underlie such selective processing to advance both theoretical and etiological
      models of anxiety. This research has particularly focused on the roles of spatial
      engagement and disengagement of attention. The relative contribution of these
      attentional components to selective processing of threat in anxious individuals
      remains unclear however. Moreover, we argue here that many of the tasks employed
      to examine these mechanisms, may not be capable of indexing the attentional
      processes that they claim to measure. In this article, we provide a
      methodological review, critically evaluating the adequacy of previous tasks
      employed to measure biased attentional engagement and disengagement. Based on a
      number of concerns raised about the ability of such tasks to differentiate these
      component attentional processes, we detail three task criteria that we believe
      are essential to be confident that a task will accurately index biased
      attentional engagement with, and disengagement from threat in anxious
      participants.

PMID- 22136159
TI  - An exonic insertion within Tex14 gene causes spermatogenic arrest in pigs.
AB  - BACKGROUND: Male infertility is an increasing problem in all domestic species
      including man. Localization and identification of genes involved in defects
      causing male infertility provide valuable information of specific events in sperm
      development. Sperm development is a complex process, where diploid spermatogonia
      develop into haploid, highly specialized spermatozoa. Correct expression and
      function of various genes and their protein products are required for production
      of fertile sperm. We have identified an infertility defect in Finnish Yorkshire
      boars caused by spermatogenic arrest. The aim of this study was to locate the
      disease associated region using genome wide screen with the PorcineSNP60 Beadchip
      and identify the causal mutation by candidate gene approach. RESULTS: In the
      Finnish Yorkshire pig population the spermatogenic arrest (SA) defect appears to
      be of genetic origin and causes severe degeneration of germ cells and total
      absence of spermatozoa. Genome wide scan with the PorcineSNP60 Beadchip localized
      the SA defect to porcine chromosome 12 in a 2 Mbp region. Sequencing of a
      candidate gene Tex14 revealed a 51 bp insertion within exon 27, which caused
      differential splicing of the exon and created a premature translation stop codon.
      The expression of Tex14 was markedly down regulated in the testis of a SA
      affected boar compared to control boars and no protein product was identified by
      Western blotting. The SA insertion sequence was also found within intron 27 in
      all analyzed animals, thus the insertion appears to be a possible duplication
      event. CONCLUSION: In this study we report the identification of a causal
      mutation for infertility caused by spermatogenic arrest at an early meiotic
      phase. Our results highlight the role of TEX14 specifically in spermatogenesis
      and the importance of specific genomic remodeling events as causes for inherited
      defects.

PMID- 22136160
TI  - Composite electronic materials based on poly(3,4-propylenedioxythiophene) and
      highly charged poly(aryleneethynylene)-wrapped carbon nanotubes for
      supercapacitors.
AB  - Supercapacitor charge storage media were fabricated using the semiconducting
      polymer poly(3,4-propylenedioxythiophene) (PProDOT) and single-walled carbon
      nanotubes (SWNTs) that were helically wrapped with ionic, conjugated poly[2,6
      {1,5-bis(3-propoxysulfonicacidsodiumsalt)}naphthylene]ethynylene (PNES). These
      PNES-wrapped SWNTs (PNES-SWNTs) enable efficient dispersion of individualized
      nanotubes in a wide range of organic solvents. PNES-SWNT film-modified Pt
      electrodes were prepared by drop casting PNES-SWNT suspensions in MeOH; high
      stability, first-generation PProDOT/PNES/SWNT composites were realized via
      electropolymerization of the ProDOT parent monomer (3,4-propylenedioxythiophene)
      in a 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide/propylene
      carbonate solution at the PNES-SWNT-modified electrode. The electrochemical
      properties of PProDOT and PProDOT/PNES/SWNT single electrodes and devices were
      examined using cyclic voltammetric methods. The hybrid composites were found to
      enhance key supercapacitor figures of merit (charge capacity and capacitance) by
      approximately a factor of 2 relative to those determined for benchmark Type I
      devices that exploited a classic PProDOT-based electrode material. The
      charge/discharge stability of the supercapacitors was probed by repeated rounds
      of cyclic voltammetric evaluation at a minimum depth of discharge of 73%; these
      experiments demonstrated that the hybrid PProDOT/PNES/SWNT composites retained
      ~90% of their initial charge capacity after 21,000 charge/discharge cycles,
      contrasting analogous data obtained for PProDOT-based devices, which showed only
      84% retention of their initial charge capacity.

PMID- 22136161
TI  - Geometrical and electrical properties of indium tin oxide clusters in ink
      dispersions.
AB  - The analysis of the TEM images of indium tin oxide (ITO) clusters in ink
      solutions deposited from ink dispersions reveals that their geometry arises from
      a diffusion limited cluster aggregation (DLCA) process. We model films of ITO
      clusters as built through deposition of DLCA clusters made of primary spherical
      nanoparticles of 13 nm in diameter. The deposition is then followed by a further
      compactification process that imitates sintering. We determine the conductivity
      of the sintered films by mapping the problem to that of the resistor network in
      which the contact regions between the touching spheres provide the dominant
      electric resistance. For a given volume fraction, conductivity of the sintered
      films is shown to be larger than that for the randomly packed spheres. However,
      the larger a typical radius of gyration of the clusters the smaller the
      enhancement. We also provide numerical tests for the routines used in the
      interpretation of the TEM images.

PMID- 22136164
TI  - The effect of frequency of calcium hydroxide dressing change and various pre- and
      inter-operative factors on the endodontic treatment of traumatized immature
      permanent incisors.
AB  - AIM: The objectives of this clinical study were as follows: (i) to determine the
      effect of frequency of calcium hydroxide [Ca(OH)(2)] dressing change on the
      apical barrier formation in immature permanent incisors with necrotic pulps and
      (ii) to investigate the effect of various clinical factors before and during
      treatment that may be associated with the frequency of Ca(OH)(2) dressing
      changes. METHODS: The study involved 21 healthy subjects, 8-12 years old. Twenty
      three immature traumatized permanent maxillary central incisors were treated
      using Ca(OH)(2) powder mixed with barium sulfate and distilled water. The
      progress of barrier formation was reviewed after 6 months of first placement of
      Ca(OH)(2) and then every 3 months until the detection of an apical barrier.
      Clinical and radiographic evaluations were performed before and after treatment.
      Data were evaluated using a chi-square test. RESULTS: Apical barrier formation
      was successful for all 23 teeth. Seventeen teeth (74%) needed only a single
      application of Ca(OH)(2), while six teeth (26%) required more than one
      application. The average time of apical barrier formation was 30 weeks, and the
      mean number of Ca(OH)(2) dressing changes was 1.3. A significant positive
      association was found between teeth that presented with displacement and the
      number of Ca(OH)(2) dressing changes (P = 0.004). CONCLUSION: An initial 6-month
      application of Ca(OH)(2) dressing followed by 3-month replacements (usually in
      teeth presenting with displacement and/or sinus tracts) may be successfully used
      in apexification treatment. This would assist in reducing the number of Ca(OH)(2)
      dressing changes, number of appointments, cost of treatment and radiation
      exposure.

PMID- 22136163
TI  - Levodopa infusion combined with entacapone or tolcapone in Parkinson disease: a
      pilot trial.
AB  - BACKGROUND AND PURPOSE: Catechol-O-methyltransferase inhibitors may be used to
      decrease levodopa requirement. The objective was to investigate whether the
      levodopa/carbidopa intestinal gel infusion dose can be reduced by 20% without
      worsening of motor fluctuations and levodopa concentration stability when oral
      catechol-O-methyltransferase inhibitors are added. METHODS: A short-term,
      randomized, partly blinded, crossover, investigator-initiated clinical trial was
      performed, with levodopa/carbidopa intestinal gel combined with oral entacapone
      and tolcapone on two different days in 10 patients. The primary outcome measure
      was difference in coefficient of variation of levodopa in plasma between
      levodopa/carbidopa, levodopa/carbidopa/entacapone, and
      levodopa/carbidopa/tolcapone. The secondary outcome measures other
      pharmacokinetic variables, patient-reported outcome, and blinded analysis of
      motor performance. RESULTS: Variation of plasma levodopa concentrations did not
      differ significantly between the treatments. The treatments did not differ
      regarding motor performance. Levodopa concentrations were significantly higher
      using tolcapone. Concentrations of the metabolite 3-O-methyldopa decreased
      gradually during catechol-O-methyltransferase inhibition. CONCLUSIONS: According
      to this small, short-term pilot study, oral catechol-O-methyltransferase
      inhibitors administered in 5-h intervals may be useful in cases where
      levodopa/carbidopa intestinal gel dose reduction is wanted. Stability of plasma
      levodopa levels is not significantly altered, and off-time is not increased when
      decreasing the levodopa/carbidopa intestinal gel dose by 20%. Rather, the dose
      should probably be decreased more than 20%, especially under tolcapone co
      treatment, to avoid increased dyskinesias with time.

PMID- 22136165
TI  - Synthesis, characterization, and calculated electronic structure of the
      crystalline metal-organic polymers [Hg(SC6H4S)(en)]n and [Pb(SC6H4S)(dien)]n.
AB  - The reaction of Hg(OAc)(2) with 1,4-benzenedithiol in ethylenediamine at 80 
      degrees C yields [Hg(SC(6)H(4)S)(en)](n), while the reaction of Pb(OAc)(2) with
      1,4-benzenedithiol in diethylenetriamine at 130  degrees C yields
      [Pb(SC(6)H(4)S)(dien)](n). Both products are crystalline materials, and structure
      determination by synchrotron X-ray powder diffraction revealed that both are
      essentially one-dimensional metal-organic polymers with -M-SC(6)H(4)S- repeat
      units. Diffuse reflectance UV-visible spectroscopy indicates band gaps of 2.89 eV
      for [Hg(SC(6)H(4)S)(en)](n) and 2.54 eV for [Pb(SC(6)H(4)S)(dien)](n), while
      density functional theory (DFT) band structure calculations yielded band gaps of
      2.24 and 2.10 eV, respectively. The two compounds are both infinite polymers of
      metal atoms linked by 1,4-benzenedithiolate, the prototypical molecule for single
      molecule conductivity studies, yet neither compound has significant electrical
      conductivity as a pressed pellet. In the case of [Pb(SC(6)H(4)S)(dien)](n)
      calculations indicate fairly flat bands and therefore low carrier mobilities,
      while the conduction band of [Hg(SC(6)H(4)S)(en)](n) does have moderate
      dispersion and a calculated electron effective mass of 0.29.m(e). Hybridization
      of the empty Hg 6s orbital with SC(6)H(4)S orbitals in the conduction band leads
      to the band dispersion, and suggests that similar hybrid materials with smaller
      band gaps will be good semiconductors.

PMID- 22136162
TI  - Immunopathogenesis of primary biliary cirrhosis: an old wives' tale.
AB  - Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by
      the autoimmune destruction of the small intrahepatic bile ducts. The disease has
      an unpredictable clinical course, but may progress to fibrosis and cirrhosis.
      Although medical treatment with urseodeoxycholic acid is largely successful, some
      patients may progress to liver failure requiring liver transplantation. PBC is
      characterised by the presence of disease specific anti-mitochondrial (AMA)
      antibodies, which are pathognomonic for PBC development. The disease demonstrates
      an overwhelming female preponderance and virtually all women with PBC present in
      middle age. The reasons for this are unknown; however several environmental and
      immunological factors may be involved. As the immune systems ages, it become less
      self tolerant, and mounts a weaker response to pathogens, possibly leading to
      cross reactivity or molecular mimicry. Some individuals display immunological
      changes which encourage the development of autoimmune disease. Risk factors
      implicated in PBC include recurrent urinary tract infection in females, as well
      as an increased prevalence of reproductive complications. These risk factors may
      work in concert with and possibly even accelerate, immune system ageing,
      contributing to PBC development. This review will examine the changes that occur
      in the immune system with ageing, paying particular attention to those changes
      which contribute to the development of autoimmune disease with increasing age.
      The review also discusses risk factors which may account for the increased female
      predominance of PBC, such as recurrent UTI and oestrogens.

PMID- 22136166
TI  - The Basel Institute for Immunology.
AB  - At the Centennial Exhibition of the Nobel Prize, the Nobel Foundation called it
      one of the ten cradles of creativity. The journal Nature likened its ideals to
      those of the French revolution--Liberte, Egalite, Fraternite--and called it a
      paradise devoted to the science of immune systems: the Basel Institute for
      Immunology (BII). Founded by Roche in 1968, inaugurated in 1971, and closed in
      2000, it was home to almost 450 scientific members, over 1,000 scientific
      visitors, and nearly 100 scientific advisors from more than 30 countries who
      worked in complete academic freedom and without commercial motives on over 3,500
      projects, publishing more than 3,200 scientific papers, almost all of them on the
      structure and functions of immune systems of different species. This review
      contains a first collection of historical facts and dates that describe the
      background of the exceptionally successful performance and the strong scientific
      impact of the institute on the field of immunology.

PMID- 22136168
TI  - Decisions about dendritic cells: past, present, and future.
AB  - A properly functioning adaptive immune system signifies the best features of
      life. It is diverse beyond compare, tolerant without fail, and capable of
      behaving appropriately with a myriad of infections and other challenges.
      Dendritic cells are required to explain how this remarkable system is energized
      and directed. I frame this article in terms of the major decisions that my
      colleagues and I have made in dendritic cell science and some of the guiding
      themes at the time the decisions were made. As a result of progress worldwide,
      there is now evidence of a central role for dendritic cells in initiating antigen
      specific immunity and tolerance. The in vivo distribution and development of a
      previously unrecognized white cell lineage is better understood, as is the
      importance of dendritic cell maturation to link innate and adaptive immunity in
      response to many stimuli. Our current focus is on antigen uptake receptors on
      dendritic cells. These receptors enable experiments involving selective targeting
      of antigens in situ and new approaches to vaccine design in preclinical and
      clinical systems.

PMID- 22136169
TI  - Comparative study of the effects of solid-state fermentation with three
      filamentous fungi on the total phenolics content (TPC), flavonoids, and
      antioxidant activities of subfractions from oats (Avena sativa L.).
AB  - The aim of present work was to investigate the effect of solid-state fermentation
      with filamentous fungi (Aspergillus oryzae var. effuses, Aspergillus oryzae, and
      Aspergillus niger) on total phenolics content (TPC), flavonoids, and antioxidant
      activities of four subfractions of oat, namely, n-hexane, ethyl acetate (EA), n
      butanol, and water, and compare them to their corresponding subfractions of
      unfermented oat. The TPC and total flavonoids increased dramatically, especially
      in EA subfractions (p < 0.05). The levels of antioxidant activity of subfractions
      were also significantly enhanced (p < 0.05). The highest antioxidant activities
      were also found in the EA subfractions. The polyphenols in EA were analyzed by
      high-performance liquid chromatography at 280 nm. Most polyphenols were increased
      remarkably, especially ferulic and caffeic acids. There was a clear correlation
      between the TPC and antioxidant activity. In conclusion, fungi fermentation is a
      potential bioprocess for increasing the TPC, flavonoids, and antioxidant
      activities of oat-based food.

PMID- 22136170
TI  - Laparoscopic gastric pouch and remnant resection: a novel approach to refractory
      anastomotic ulcers after Roux-en-Y gastric bypass: case report.
AB  - BACKGROUND: Anastomotic or marginal ulcers occur in 0.6 to 16% of patients after
      laparoscopic Roux-en-Y-Gastric Bypass. Initial therapy aims at eliminating known
      risk factors including smoking, Helicobacter pylori infection, use of non
      steroidal anti-inflammatory drugs and inhibition of gastric acid secretion. While
      this approach is successful in 68 to 88% of the cases, up to one third of
      patients need a subsequent surgical revision. However, marginal ulcers still
      recur in up to 10% of cases after revisional surgery, thus constituting a serious
      challenge for bariatric surgeons. CASE PRESENTATION: We herein report a case of
      an insidious marginal ulcer refractory to both medical therapy with high-dosed
      proton pump inhibitors and sucralfate as well as surgical therapy consisting of
      the lengthening of a short alimentary limb and later resection of the
      gastroenterostomy and construction of a new tension-free anastomosis. Only after
      gastrectomy by laparoscopic en-bloc resection of the gastrojejunostomy, the
      gastric pouch and resection of the gastric remnant with reconstruction by
      esophagojejunostomy the patient remained free of symptoms. CONCLUSION: By
      laparoscopic resection of the entire gastric pouch and the gastric remnant the
      risk to leave a suboptimally vascularised or even ischemic pouch in situ was
      avoided. The esophagojejunostomy was then created in healthy, good vascularised
      tissue. In our case this novel approach was effective in the management of a
      refractory anastomotic ulcer and might represent a rescue option when simple
      revision of the gastrojejunostomy fails.

PMID- 22136167
TI  - Regulation of immune responses by mTOR.
AB  - mTOR is an evolutionarily conserved serine/threonine kinase that plays a central
      role in integrating environmental cues in the form of growth factors, amino
      acids, and energy. In the study of the immune system, mTOR is emerging as a
      critical regulator of immune function because of its role in sensing and
      integrating cues from the immune microenvironment. With the greater appreciation
      of cellular metabolism as an important regulator of immune cell function, mTOR is
      proving to be a vital link between immune function and metabolism. In this
      review, we discuss the ability of mTOR to direct the adaptive immune response.
      Specifically, we focus on the role of mTOR in promoting differentiation,
      activation, and function in T cells, B cells, and antigen-presenting cells.

PMID- 22136172
TI  - Chemical composition and antibacterial activity of a hexane extract of Tunisian
      caprifig latex from the unripe fruit of Ficus carica.
AB  - CONTEXT: The plant kingdom has become a target in the search for new drugs and
      biologically active lead compounds. The common Jrani Tunisian caprifig Ficus
      carica L. (Moraceae) is one of the large number of plant species that are used in
      folklore medicine yet to be investigated for the treatment of many diseases,
      including those of infectious nature. OBJECTIVE: Hexane extract of the Tunisian
      common Jrani caprifig latex was assayed for antibacterial activity against
      several Gram-positive and Gram-negative bacteria. Chemical composition of the
      extract was also investigated. MATERIALS AND METHODS: The hexane extract was
      obtained from Tunisian Jrani caprifig latex by maceration, and then analyzed by
      gas chromatography-mass spectrometry. The extract was tested in vitro for
      antibacterial activity by the disc diffusion method and minimal inhibitory
      concentration (MIC) was also determined for all the test cultures. RESULTS:
      Thirty-six compounds of the extract were identified, 90.56% of the total area of
      peaks were coumarins. A strong bactericidal effect was demonstrated. The most
      sensitive bacteria were Staphylococcus saprophyticus clinical isolate, and
      Staphylococcus aureus ATCC 25923, with a MIC of 19 ug/mL. DISCUSSION AND
      CONCLUSION: These findings demonstrate an effective in vitro antibacterial
      activity of the hexane extract of caprifig latex.

PMID- 22136171
TI  - Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile
      ducts: an anatomical in situ study yielding evidence of maturational lineages.
AB  - Stem/progenitors have been identified intrahepatically in the canals of Hering
      and extrahepatically in glands of the biliary tree. Glands of the biliary tree
      (peribiliary glands) are tubulo-alveolar glands with mucinous and serous acini,
      located deep within intrahepatic and extrahepatic bile ducts. We have shown that
      biliary tree stem/progenitors (BTSCs) are multipotent, giving rise in vitro and
      in vivo to hepatocytes, cholangiocytes or pancreatic islets. Cells with the
      phenotype of BTSCs are located at the bottom of the peribiliary glands near the
      fibromuscular layer. They are phenotypically heterogeneous, expressing
      transcription factors as well as surface and cytoplasmic markers for
      stem/progenitors of liver (e.g. SOX9/17), pancreas (e.g. PDX1) and endoderm (e.g.
      SOX17, EpCAM, NCAM, CXCR4, Lgr5, OCT4) but not for mature markers (e.g. albumin,
      secretin receptor or insulin). Subpopulations co-expressing liver and pancreatic
      markers (e.g. PDX1(+)/SOX17(+)) are EpCAM(+/-), and are assumed to be the most
      primitive of the BTSC subpopulations. Their descendants undergo a maturational
      lineage process from the interior to the surface of ducts and vary in the mature
      cells generated: pancreatic cells in hepatopancreatic ducts, liver cells in large
      intrahepatic bile ducts, and bile duct cells along most of the biliary tree. We
      hypothesize that there is ongoing organogenesis throughout life, with BTSCs
      giving rise to hepatic stem cells in the canals of Hering and to committed
      progenitors within the pancreas. The BTSCs are likely to be central to normal
      tissue turnover and injury repair and to be key elements in the pathophysiology
      of liver, pancreas and biliary tree diseases, including oncogenesis.

PMID- 22136173
TI  - Electrocardiographic determinants of the polymorphic QRS morphology in idiopathic
      right ventricular outflow tract tachycardia.
AB  - INTRODUCTION: Premature ventricular contractions (PVCs) arising from the right
      ventricular outflow tract (RVOT) can trigger polymorphic ventricular tachycardia
      (PVT) or ventricular fibrillation (VF) in patients with no structural heart
      disease. We aimed to clarify the ECG determinants of the polymorphic QRS
      morphology in idiopathic RVOT PVT/VF. METHODS AND RESULTS: The ECG parameters
      were compared between 18 patients with idiopathic PVT/VF (PVT-group) and 21 with
      monomorphic VT arising from the RVOT (MVT-group). The coupling interval (CI) of
      the first VT beat was comparable between the 2 groups. However, the prematurity
      index (PI) of the first VT beat was smaller in the PVT-group than in the MVT
      group (P < 0.001). Furthermore, the QT index, defined as the ratio of the CI to
      the QT interval of the preceding sinus complex, was also smaller for the PVT/VF
      in the PVT-group than that for the VT in the MVT-group (P < 0.01). In the PVT
      group, the CI of the first VT beat was comparable between that of VT and isolated
      PVCs, but the PI of the first VT beat was shorter for VT than isolated PVCs (P <
      0.05). The PI was the only independent determinant of the polymorphic QRS
      morphology (odd ratio = 2.198; 95% confidence interval = 1.321-3.659; P = 0.002).
      CONCLUSION: The smaller PIs of the first VT beat may result in a polymorphic QRS
      morphology.

PMID- 22136174
TI  - Several prescription patterns of antipsychotic drugs influence cognitive
      functions in Japanese chronic schizophrenia patients.
AB  - OBJECTIVE: We hypothesized that an excessive dose of antipsychotic drug and/or a
      larger number of antipsychotic drug worsens cognitive functions in schizophrenia
      patients. To confirm the hypothesis, we compared several cognitive functions in
      the patients taking a second-generation antipsychotic drug (SGA) only (SGA
      monotherapy group) with those in patients taking more than two kinds of
      antipsychotic drugs (polypharmacy group). METHODS: The cognitive functions of 136
      chronic schizophrenia patients were evaluated using the Brief Assessment of
      Cognition in Schizophrenia, Japanese-language version (BACS-J). RESULTS: A
      significantly negative correlation was found between the composite score in the
      BACS-J and the chlorpromazine equivalence of doses of antipsychotic drugs in
      whole patients (r = -0.43, P < 0.001). Schizophrenia patients in the polypharmacy
      group had lower composite scores than those in the SGA monotherapy group in the
      BACS-J. No difference was observed in the composite score and the primary score
      in each item in the BACS-J between patients with first- plus second-generation
      antipsychotic drug (FGA + SGA group) and those with two kinds of SGA (SGA + SGA
      group). CONCLUSION: These results suggest that an excessive dose of antipsychotic
      drugs regardless of FGA and SGA might cause the deterioration of cognitive
      functions in chronic Japanese schizophrenia patients.

PMID- 22136176
TI  - The mechanisms of antihyperalgesic effect of topiramate in a rat model of
      inflammatory hyperalgesia.
AB  - Recent studies have shown that topiramate, a structurally novel anticonvulsant,
      exerts antinociceptive activity in animal models of neuropathic, acute somatic,
      and visceral pain. This study was aimed to examine: (i) the effects of
      systemically and locally peripherally administered topiramate in the rat
      inflammatory pain model and (ii) the potential role and site(s) of gamma
      aminobutyric acid (GABA), opioid, and adrenergic receptors in topiramate's
      antihyperalgesia. Rats received intraplantar (i.pl.) injections of the pro
      inflammatory compound carrageenan. A paw pressure test was used to determine: (i)
      the effect of systemic and local peripheral topiramate on carrageenan-induced
      hyperalgesia and (ii) the effects of systemic and local peripheral bicuculline
      (selective GABAA receptor antagonist), naloxone (nonselective opioid receptor
      antagonist), and yohimbine (selective alpha2-adrenergic receptor antagonist) on
      topiramate-induced antihyperalgesia. Systemic topiramate (40-160 mg/kg; p.o.)
      produced a significant dose-dependent reduction in the paw inflammatory
      hyperalgesia induced by carrageenan. The antihyperalgesic effect of systemic
      topiramate was significantly decreased by systemic bicuculline (0.5-1 mg/kg;
      i.p.), naloxone (2-5 mg/kg; i.p.), and yohimbine (1-3 mg/kg; i.p.). Local
      peripheral topiramate (0.03-0.34 mg/paw; i.pl.) also produced significant dose
      dependent antihyperalgesia, which was significantly depressed by local peripheral
      yohimbine (0.05-0.2 mg/paw; i.pl.) but not by local peripheral bicuculline (0.15
      mg/paw; i.pl.) or naloxone (0.1 mg/paw; i.pl.). The results suggest that
      topiramate produces systemic and local peripheral antihyperalgesia in an
      inflammatory pain model, which is, at least partially, mediated by central GABAA
      and opioid receptors and by peripheral and most probably central alpha2
      adrenergic receptors. These findings contribute to better understanding of
      topiramate's action in pain states involving inflammation.

PMID- 22136175
TI  - Permanent genetic resources added to Molecular Ecology Resources Database 1
      August 2011-30 September 2011.
AB  - This article documents the addition of 299 microsatellite marker loci and nine
      pairs of single-nucleotide polymorphism (SNP) EPIC primers to the Molecular
      Ecology Resources (MER) Database. Loci were developed for the following species:
      Alosa pseudoharengus, Alosa aestivalis, Aphis spiraecola, Argopecten purpuratus,
      Coreoleuciscus splendidus, Garra gotyla, Hippodamia convergens, Linnaea borealis,
      Menippe mercenaria, Menippe adina, Parus major, Pinus densiflora, Portunus
      trituberculatus, Procontarinia mangiferae, Rhynchophorus ferrugineus,
      Schizothorax richardsonii, Scophthalmus rhombus, Tetraponera aethiops,
      Thaumetopoea pityocampa, Tuta absoluta and Ugni molinae. These loci were cross
      tested on the following species: Barilius bendelisis, Chiromantes haematocheir,
      Eriocheir sinensis, Eucalyptus camaldulensis, Eucalyptus cladocalix, Eucalyptus
      globulus, Garra litaninsis vishwanath, Garra para lissorhynchus, Guindilla
      trinervis, Hemigrapsus sanguineus, Luma chequen. Guayaba, Myrceugenia
      colchaguensis, Myrceugenia correifolia, Myrceugenia exsucca, Parasesarma
      plicatum, Parus major, Portunus pelagicus, Psidium guayaba, Schizothorax
      richardsonii, Scophthalmus maximus, Tetraponera latifrons, Thaumetopoea bonjeani,
      Thaumetopoea ispartensis, Thaumetopoea libanotica, Thaumetopoea pinivora,
      Thaumetopoea pityocampa ena clade, Thaumetopoea solitaria, Thaumetopoea
      wilkinsoni and Tor putitora. This article also documents the addition of nine
      EPIC primer pairs for Euphaea decorata, Euphaea formosa, Euphaea ornata and
      Euphaea yayeyamana.

PMID- 22136177
TI  - Supersensitive gastrin assay using antibodies raised against a cholecystokinin
      homolog.
AB  - Peptide hormones may occur in particularly low amounts in samples from small
      animals. Hence, in a rat microdialysis study conventional immunoassays were not
      sufficiently sensitive to measure gastrin in the dialysis samples. We therefore
      exploited the observation that antibodies raised against the homologous hormone
      cholecystokinin (CCK) occasionally bind gastrin peptides with significantly
      higher affinity than the proper ligand. The immunoassay thus established could
      detect 1.0 pmol/l in 15 MUl microdialysate, which corresponds to 23 attomol
      gastrin. Such detection limit is five-fold lower than that obtained with the most
      avid conventional gastrin antibodies. The results may encourage similar
      approaches for other peptides using homologue-raised antibodies when
      supersensitivity is required.

PMID- 22136178
TI  - Enantioselective total synthesis of (+)-scuteflorin A using organocatalytic
      asymmetric epoxidation.
AB  - We report the first enantioselective total synthesis of (+)-scuteflorin A in 14%
      overall yield, employing a chiral iminium salt to effect an organocatalytic
      asymmetric epoxidation of xanthyletin in >99% ee as the key step.

PMID- 22136179
TI  - Why radiography should no longer be considered a surrogate outcome measure for
      longitudinal assessment of cartilage in knee osteoarthritis.
AB  - Imaging of cartilage has traditionally been achieved indirectly with conventional
      radiography. Loss of joint space width, or 'joint space narrowing', is considered
      a surrogate marker for cartilage thinning. However, radiography is severely
      limited by its inability to visualize cartilage, the difficulty of ascertaining
      the optimum and reproducible positioning of the joint in serial assessments, and
      the difficulty of grading joint space narrowing visually. With the availability
      of advanced magnetic resonance imaging (MRI) scanners, new pulse sequences, and
      imaging techniques, direct visualization of cartilage has become possible. MRI
      enables visualization not only of cartilage but also of other important features
      of osteoarthritis simultaneously. 'Pre-radiographic' cartilage changes depicted
      by MRI can be measured reliably by a semiquantitative or quantitative approach.
      MRI enables accurate measurement of longitudinal changes in quantitative
      cartilage morphology in knee osteoarthritis. Moreover, compositional MRI allows
      imaging of 'pre-morphologic' changes (that is, visualization of subtle
      intrasubstance matrix changes before any obvious morphologic alterations occur).
      Detection of joint space narrowing on radiography seems outdated now that it is
      possible to directly visualize morphologic and pre-morphologic changes of
      cartilage by using conventional as well as complex MRI techniques.

PMID- 22136181
TI  - Occluded uterine rupture: preventing catastrophe, preventing early diagnosis.

PMID- 22136180
TI  - Analysis of substrate access to active sites in bacterial multicomponent
      monooxygenase hydroxylases: X-ray crystal structure of xenon-pressurized phenol
      hydroxylase from Pseudomonas sp. OX1.
AB  - In all structurally characterized bacterial multicomponent monooxygenase (BMM)
      hydroxylase proteins, a series of hydrophobic cavities in the alpha-subunit trace
      a conserved path from the protein exterior to the carboxylate-bridged diiron
      active site. This study examines these cavities as a potential route for
      transport of dioxygen to the active site by crystallographic characterization of
      a xenon-pressurized sample of the hydroxylase component of phenol hydroxylase
      from Pseudomonas sp. OX1. Computational analyses of the hydrophobic cavities in
      the hydroxylase alpha-subunits of phenol hydroxylase (PHH), soluble methane
      monooxygenase (MMOH), and toluene/o-xylene monooxygenase (ToMOH) are also
      presented. The results, together with previous findings from crystallographic
      studies of xenon-pressurized sMMO hydroxylase, clearly identify the propensity
      for these cavities to bind hydrophobic gas molecules in the protein interior.
      This proposed functional role is supported by recent stopped flow kinetic studies
      of ToMOH variants [Song, W. J., et al. (2011) Proc. Natl. Acad. Sci. U.S.A.108,
      14795-14800]. In addition to information about the Xe sites, the structure
      determination revealed significantly weakened binding of regulatory protein to
      the hydroxylase in comparison to that in the previously reported structure of
      PHH, as well as the presence of a newly identified metal-binding site in the
      alpha-subunit that adopts a linear coordination environment consistent with
      Cu(I), and a glycerol molecule bound to Fe1 in a fashion that is unique among
      hydrocarbon-diiron site adducts reported to date in BMM hydroxylase structures.
      Finally, a comparative analysis of the alpha-subunit structures of PHH, MMOH, and
      ToMOH details proposed routes for the other three BMM substrates, the
      hydrocarbon, electrons, and protons, comprising cavities, channels, hydrogen
      bonding networks, and pores in the structures of their alpha-subunits.

PMID- 22136182
TI  - Benefit-risk assessment of bevacizumab in the treatment of breast cancer.
AB  - An evaluation of the benefit-versus-risk of bevacizumab in the treatment of
      advanced breast cancer is timely and relevant. Recently, the US FDA has withdrawn
      the approval of bevacizumab as a therapeutic option for the treatment of advanced
      breast cancer, generating controversy in the scientific community. Although the
      pivotal study (Eastern Cooperative Oncology Group 2100 trial [E2100]) had shown
      doubling of the progression-free survival when bevacizumab was added to
      chemotherapy, this magnitude of benefit could not be replicated in subsequent
      studies. Furthermore, individual studies and meta-analyses failed to demonstrate
      an overall survival benefit with the addition of bevacizumab to different
      chemotherapy regimens. In addition, this agent is associated with an increased
      incidence of serious adverse events such as hypertension, congestive heart
      failure and thromboembolism, and its cost is likely to be a consideration in its
      use for many patients worldwide. Retrospective biomarker-based studies aiming to
      identify the subpopulation of patients most likely to benefit from the addition
      of bevacizumab to standard chemotherapy in breast cancer should be a research
      priority.

PMID- 22136183
TI  - Identifying adverse events of vaccines using a Bayesian method of medically
      guided information sharing.
AB  - BACKGROUND: The detection of adverse events following immunization (AEFI)
      fundamentally depends on how these events are classified. Standard methods impose
      a choice between either grouping similar events together to gain power or
      splitting them into more specific definitions. We demonstrate a method of
      medically guided Bayesian information sharing that avoids grouping or splitting
      the data, and we further combine this with the standard epidemiological tools of
      stratification and multivariate regression. OBJECTIVE: The aim of this study was
      to assess the ability of a Bayesian hierarchical model to identify
      gastrointestinal AEFI in children, and then combine this with testing for effect
      modification and adjustments for confounding. STUDY DESIGN: Reporting odds ratios
      were calculated for each gastrointestinal AEFI and vaccine combination. After
      testing for effect modification, these were then re-estimated using multivariable
      logistic regression adjusting for age, sex, year and country of report. A
      medically guided hierarchy of AEFI terms was then derived to allow information
      sharing in a Bayesian model. SETTING: All spontaneous reports of AEFI in children
      under 18 years of age in the WHO VigiBaseTM (Uppsala Monitoring Centre, Uppsala,
      Sweden) before June 2010. Reports with missing age were included in the main
      analysis in a separate category and excluded in a subsequent sensitivity
      analysis. EXPOSURES: The 15 most commonly prescribed childhood vaccinations,
      excluding influenza vaccines. MAIN OUTCOME MEASURES: All gastrointestinal AEFI
      coded by WHO Adverse Reaction Terminology. RESULTS: A crude analysis identified
      132 signals from 655 reported combinations of gastrointestinal AEFI. Adjusting
      for confounding by age, sex, year of report and country of report, where
      appropriate, reduced the number of signals identified to 88. The addition of a
      Bayesian hierarchical model identified four further signals and removed three.
      Effect modification by age and sex was identified for six vaccines for the
      outcomes of vomiting, nausea, diarrhoea and salivary gland enlargement.
      CONCLUSION: This study demonstrated a sequence of methods for routinely analysing
      spontaneous report databases that was easily understandable and reproducible. The
      combination of classical and Bayesian methods in this study help to focus the
      limited resources for hypothesis testing studies towards adverse events with the
      strongest support from the data.

PMID- 22136184
TI  - Terminological challenges in safety surveillance.

PMID- 22136185
TI  - Screening of thyroid nodules by serum calcitonin measurements: why not?

PMID- 22136186
TI  - A novel cross-shear metric for application in computer simulation of ultra-high
      molecular weight polyethylene wear.
AB  - Wear testing of polyethylene in total joint replacements is common and required
      for any new device. Computational wear modelling has obvious utility in this
      context as it can be conducted with much greater economy than physical testing.
      Archard's law has become the accepted standard for wear simulation in total
      joints but it does not account for cross-shear, which is known to increase wear
      significantly relative to unidirectional sliding. The purpose of this study was
      to develop a robust cross-shear model applicable to any interface geometry under
      any kinematic conditions. The proposed metric, x (*), is distinguished from
      existing cross-shear models by the fact that it measures cross-path motion
      incrementally throughout a motion cycle and quantifies cross-shear based on
      incremental changes in sliding direction. Validation showed strong support for
      the predictive capability of x (*) when applied to pin-on-disc test data.

PMID- 22136187
TI  - Mesoscopic simulations of the phase behavior of aqueous EO19PO29EO19 solutions
      confined and sheared by hydrophobic and hydrophilic surfaces.
AB  - The MesoDyn method is used to investigate associative structures in aqueous
      solution of a nonionic triblock copolymer consisting of poly(propylene oxide)
      capped on both ends with poly(ethylene oxide) chains. The effect of adsorbing
      (hydrophobic) and nonadsorbing (hydrophilic) solid surfaces in contact with
      aqueous solutions of the polymer is elucidated. The macromolecules form self
      assembled structures in solution. Confinement under shear forces is investigated
      in terms of interfacial behavior and association. The formation of micelles under
      confinement between hydrophilic surfaces occurs faster than in bulk aqueous
      solution while layered structures assemble when the polymers are confined between
      hydrophobic surfaces. Micelles are deformed under shear rates of 1 MUs(-1) and
      eventually break to form persistent, adsorbed layered structures. As a result,
      surface damage under frictional forces is prevented. Overall, this study
      indicates that aqueous triblock copolymers of poly(ethylene oxide) (PEO) and
      poly(propylene oxide) (PPO) (Pluronics, EO(m)PO(n)EO(m)) act as a boundary
      lubricant for hydrophobic surfaces but not for hydrophilic ones.

PMID- 22136188
TI  - Involvement of remnant spleen volume on the progression of steatohepatitis in
      diet-induced obese rats after a splenectomy.
AB  - AIM:   This study investigated the correlation between remnant spleen volume
      after splenectomy (SPX) and the degree of hepatic steatosis and/or inflammation.
      METHODS:   Male Sprague-Dawley rats were fed HF food and divided into three
      groups: sham-operation (Sham) group, a hemisplenectomy (H-SPX) group, and a total
      splenectomy (T-SPX) group. Serum was collected and livers removed 12 weeks after
      surgery. We measured serum lipid markers and evaluated liver changes by comparing
      the three groups. Additionally, we examined liver changes 24 weeks after SPX.
      RESULTS:   Serum triglyceride and free fatty acid levels after SPX were higher
      than those of sham controls, and a significant difference was found between T-SPX
      and the other groups (P < 0.05 for each). Increased intrahepatic fat accumulation
      was shown in SPX rats along with lower residual spleen volume; this fat
      accumulation after SPX was accelerated in rats at 24 weeks. Additionally, liver
      inflammatory changes, including an increase in the Kupffer cell population and
      pro-inflammatory cytokine production, as well as a high level of oxidative
      stress, were observed in the liver sections from SPX rats, which correlated
      significantly with less volume of the residual spleen. Also, an increase in pro
      inflammatory cytokine content and a decrease in anti-inflammatory cytokine
      content were shown in the residual spleen from H-SPX rats, as compared to those
      of sham controls (P < 0.05 for each). CONCLUSION:   These results indicate the
      importance of preserving splenic tissue. This residual spleen may play an
      important role in preventing the progression from diet-induced hepatic steatosis
      to steatohepatitis.

PMID- 22136189
TI  - Intra- and interfamily phenotypic diversity in pain syndromes associated with a
      gain-of-function variant of NaV1.7.
AB  - BACKGROUND: Sodium channel NaV1.7 is preferentially expressed within dorsal root
      ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine
      diamter axons, where it acts as a threshold channel, amplifying stimuli such as
      generator potentials in nociceptors. Gain-of-function mutations and variants
      (single amino acid substitutions) of NaV1.7 have been linked to three pain
      syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder
      (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by
      burning pain and redness that is usually focused on the distal extremities,
      precipitated by mild warmth and relieved by cooling, and is caused by mutations
      that hyperpolarize activation, slow deactivation, and enhance the channel ramp
      response. PEPD is characterized by perirectal, periocular or perimandibular pain,
      often triggered by defecation or lower body stimulation, and is caused by
      mutations that severely impair fast-inactivation. SFN presents a clinical picture
      dominated by neuropathic pain and autonomic symptoms; gain-of-function variants
      have been reported to be present in approximately 30% of patients with biopsy
      confirmed idiopathic SFN, and functional testing has shown altered fast
      inactivation, slow-inactivation or resurgent current. In this paper we describe
      three patients who house the NaV1.7/I228M variant. METHODS: We have used clinical
      assessment of patients, quantitative sensory testing and skin biopsy to study
      these patients, including two siblings in one family, in whom genomic screening
      demonstrated the I228M NaV1.7 variant. Electrophysiology (voltage-clamp and
      current-clamp) was used to test functional effects of the variant channel.
      RESULTS: We report three different clinical presentations of the I228M NaV1.7
      variant: presentation with severe facial pain, presentation with distal (feet,
      hands) pain, and presentation with scalp discomfort in three patients housing
      this NaV1.7 variant, two of which are from a single family. We also demonstrate
      that the NaV1.7/I228M variant impairs slow-inactivation, and produces
      hyperexcitability in both trigeminal ganglion and DRG neurons. CONCLUSION: Our
      results demonstrate intra- and interfamily phenotypic diversity in pain syndromes
      produced by a gain-of-function variant of NaV1.7.

PMID- 22136190
TI  - Identification of dysfunctional modules and disease genes in congenital heart
      disease by a network-based approach.
AB  - BACKGROUND: The incidence of congenital heart disease (CHD) is continuously
      increasing among infants born alive nowadays, making it one of the leading causes
      of infant morbidity worldwide. Various studies suggest that both genetic and
      environmental factors lead to CHD, and therefore identifying its candidate genes
      and disease-markers has been one of the central topics in CHD research. By using
      the high-throughput genomic data of CHD which are available recently, network
      based methods provide powerful alternatives of systematic analysis of complex
      diseases and identification of dysfunctional modules and candidate disease genes.
      RESULTS: In this paper, by modeling the information flow from source disease
      genes to targets of differentially expressed genes via a context-specific protein
      protein interaction network, we extracted dysfunctional modules which were then
      validated by various types of measurements and independent datasets. Network
      topology analysis of these modules revealed major and auxiliary pathways and
      cellular processes in CHD, demonstrating the biological usefulness of the
      identified modules. We also prioritized a list of candidate CHD genes from these
      modules using a guilt-by-association approach, which are well supported by
      various kinds of literature and experimental evidence. CONCLUSIONS: We provided a
      network-based analysis to detect dysfunctional modules and disease genes of CHD
      by modeling the information transmission from source disease genes to targets of
      differentially expressed genes. Our method resulted in 12 modules from the
      constructed CHD subnetwork. We further identified and prioritized candidate
      disease genes of CHD from these dysfunctional modules. In conclusion, module
      analysis not only revealed several important findings with regard to the
      underlying molecular mechanisms of CHD, but also suggested the distinct network
      properties of causal disease genes which lead to identification of candidate CHD
      genes.

PMID- 22136191
TI  - Lip cancer: retrospective analysis of 181 cases.
AB  - BACKGROUND: In Germany little data on the epidemiology and histology of lip
      cancers are available, as lip cancers are commonly pooled together with head and
      neck tumors. PATIENTS AND METHODS: Retrospective analysis of 181 patients with
      malignant tumors of the lips with respect to gender, location, histology, risk
      factors and comorbidity. RESULTS: There were 90 women and 91 men with a mean age
      of 71 years. 98 had a tumor on the upper lip and 83 patients on the lower lip.
      Tumors of the upper lip showed a slight female preference (61%). In contrast
      lower lip cancer was more common (64%) in men. Histological analysis revealed
      that in both regions nodular basal cell carcinomas as well as squamous cell
      carcinomas (NOS) are the most common subtypes. Vertical tumor thickness of
      squamous cell carcinomas was in most cases smaller than 6 mm (n = 71) and only in
      4 cases was a tumor thickness of >6 mm detected. Altogether, 57% of the patients
      reported a high to very high sun exposure. CONCLUSIONS: In comparison to previous
      studies we found a weaker preference for women for tumors of the upper lip and
      also a weaker preference for men for tumors of the lower lip. The causes remain
      unclear, but could be causally related to an increased life expectancy and/or
      changed risk profile.

PMID- 22136192
TI  - Role of adsorbed surfactant in the reaction of aryl diazonium salts with single
      walled carbon nanotubes.
AB  - Because covalent chemistry can diminish the optical and electronic properties of
      single-walled carbon nanotubes (SWCNTs), there is significant interest in
      developing methods of controllably functionalizing the nanotube sidewall. To
      date, most attempts at obtaining such control have focused on reaction
      stoichiometry or strength of oxidative treatment. Here, we examine the role of
      surfactants in the chemical modification of single-walled carbon nanotubes with
      aryl diazonium salts. The adsorbed surfactant layer is shown to affect the
      diazonium derivatization of carbon nanotubes in several ways, including
      electrostatic attraction or repulsion, steric exclusion, and direct chemical
      modification of the diazonium reactant. Electrostatic effects are most pronounced
      in the cases of anionic sodium dodecyl sulfate and cationic
      cetyltrimethylammonium bromide, where differences in surfactant charge can
      significantly affect the ability of the diazonium ion to access the SWCNT
      surface. For bile salt surfactants, with the exception of sodium cholate, we find
      that the surfactant wraps tightly enough such that exclusion effects are
      dominant. Here, sodium taurocholate exhibits almost no reactivity under the
      explored reaction conditions, while for sodium deoxycholate and sodium
      taurodeoxycholate, we show that the greatest extent of reaction is observed among
      a small population of nanotube species, with diameters between 0.88 and 0.92 nm.
      The anomalous reaction of nanotubes in this diameter range seems to imply that
      the surfactant is less effective at coating these species, resulting in a reduced
      surface coverage on the nanotube. Contrary to the other bile salts studied,
      sodium cholate enables high selectivity toward metallic species and small band
      gap semiconductors, which is attributed to surfactant-diazonium coupling to form
      highly reactive diazoesters. Further, it is found that the rigidity of anionic
      surfactants can significantly influence the ability of the surfactant layer to
      stabilize the diazonium ion near the nanotube surface. Such Coulombic and
      surfactant packing effects offer promise toward employing surfactants to
      controllably functionalize carbon nanotubes.

PMID- 22136193
TI  - Summary of roundtable discussion meeting: non-human primates to assess risk for
      EBV-related lymphomas in humans.
AB  - Epstein-Barr virus (EBV)-associated lymphomas are a known risk for
      immunosuppressed individuals. Non-clinical methods to determine the potential of
      new immunomodulatory compounds to produce EBV-associated lymphomas (hazard
      identification) have not been developed. Since lymphocryptovirus (LCV) in non
      human primates (NHP) has similar characteristics to EBV in humans, a Roundtable
      meeting was held in October 2010 to explore how the potential for EBV-related
      lymphomas in humans can be assessed by using surrogate biomarkers for lymphoma
      risk in NHP toxicity studies. Stakeholders from regulatory agencies, academia,
      and industry came together to determine the research gaps and potential benefits
      and considerations of such an approach given the current state-of-the-science.
      Key conclusions from the discussion included considerations raised about the
      potential usefulness of LCV-related biomarkers from NHP studies since there is
      significant controversy over the reliability of using EBV viral load or EBV
      specific T-lymphocytes to predict for lymphoproliferative disorders in transplant
      patients. In addition, there are technical challenges that need to be further
      addressed in order to develop methods to measure LCV viral load and LCV-specific
      T-lymphocytes from cynomolgus monkeys.

PMID- 22136194
TI  - Visible-light generation of the naked 12-electron fragment C5H5Fe+: alkyne-to
      vinylidene isomerization and synthesis of polynuclear iron vinylidene and alkynyl
      complexes including hexairon stars.
AB  - Visible-light photolysis of [FeCp(eta(6)-C(6)H(5)CH(3))][PF(6)] using a simple
      100-W bulb or a compact fluorescent light bulb in the presence of terminal
      alkynes and dppe yielded the vinylidene complexes [FeCp(?C?CHR)(dppe)][PF(6)]
      that were deprotonated by t-BuOK to yield the alkynyl complexes [FeCp(
      C=CR)(dppe)]. The reaction has been extended to the synthesis of bis-, tris,
      tetra-, and hexanuclear iron complexes including three alkynes of the ferrocenyl
      family.

PMID- 22136195
TI  - RibM from Streptomyces davawensis is a riboflavin/roseoflavin transporter and may
      be useful for the optimization of riboflavin production strains.
AB  - BACKGROUND: The bacterium Bacillus subtilis, which is not a natural riboflavin
      overproducer, has been converted into an excellent production strain by classical
      mutagenesis and metabolic engineering. To our knowledge, the enhancement of
      riboflavin excretion from the cytoplasm of overproducing cells has not yet been
      considered as a target for (further) strain improvement. Here we evaluate the
      flavin transporter RibM from Streptomyces davawensis with respect to improvement
      of a riboflavin production strain. RESULTS: The gene ribM from S. davawensis,
      coding for a putative facilitator of riboflavin uptake, was codon optimized
      (ribMopt) for expression in B. subtilis. The gene ribMopt was functionally
      introduced into B. subtilis using the isopropyl-beta-thiogalactopyranoside (IPTG)
      inducible expression plasmid pHT01: Northern-blot analysis of total RNA from IPTG
      treated recombinant B. subtilis cells revealed a ribMopt specific transcript.
      Western blot analysis showed that the his6-tagged heterologous gene product RibM
      was present in the cytoplasmic membrane. Expression of ribM in Escherichia coli
      increased [14C]riboflavin uptake, which was not affected by the protonophore
      carbonyl cyanide m-chlorophenylhydrazone (CCCP). Expression of ribMopt supported
      growth of a B. subtilis DeltaribB::Ermr DeltaribU::Kanr double mutant deficient
      in riboflavin synthesis (DeltaribB) and also deficient with respect to riboflavin
      uptake (DeltaribU). Expression of ribMopt increased roseoflavin (a toxic
      riboflavin analog produced by S. davawensis) sensitivity of a B. subtilis
      DeltaribU::Kanr strain. Riboflavin synthesis by a model riboflavin B. subtilis
      production strain overproducing RibM was increased significantly depending on the
      amount of the inducer IPTG. CONCLUSIONS: The energy independent flavin
      facilitator RibM could in principle catalyze riboflavin export and thus may be
      useful to increase the riboflavin yield in a riboflavin production process using
      a recombinant RibM overproducing B. subtilis strain (or any other microorganism).

PMID- 22136196
TI  - Isolating neural components of threat bias in pediatric anxiety.
AB  - BACKGROUND:   Attention biases toward threat are often detected in individuals
      with anxiety disorders. Threat biases can be measured experimentally through dot
      probe paradigms, in which individuals detect a probe following a stimulus pair
      including a threat. On these tasks, individuals with anxiety tend to detect
      probes that occur in a location previously occupied by a threat (i.e., congruent)
      faster than when opposite threats (i.e., incongruent). In pediatric anxiety
      disorders, dot-probe paradigms detect abnormal attention biases toward threat and
      abnormal ventrolateral prefrontal cortex (vlPFC) function. However, it remains
      unclear if this aberrant vlPFC activation occurs while subjects process threats
      (e.g., angry faces) or, alternatively, while they process and respond to probes.
      This magnetoencephalography (MEG) study was designed to answer this question.
      METHODS:   Adolescents with either generalized anxiety disorder (GAD, n = 17) or
      no psychiatric diagnosis (n = 25) performed a dot-probe task involving angry and
      neutral faces while MEG data were collected. Synthetic Aperture Magnetometry
      (SAM) beamformer technique was used to determine whether there were group
      differences in power ratios while subjects processed threats (i.e., angry vs.
      neutral faces) or when subjects responded to incongruent versus. congruent
      probes. RESULTS:   Group differences in vlPFC activation during the response
      period emerged with a 1-30 Hz frequency band. No group differences in vlPFC
      activation were detected in response to angry-face cues. CONCLUSIONS:   In the
      dot-probe task, anxiety-related perturbations in vlPFC activation reflect
      abnormal attention control when responding to behaviorally relevant probes, but
      not to angry faces. Given that motor responses to these probes are used to
      calculate threat bias, this study provides insight into the pathophysiology
      reflected in this commonly used marker of anxiety. In addition, this finding may
      inform the development of novel anxiety-disorder treatments targeting the vlPFC
      to enhance attention control to task-relevant demands.

PMID- 22136197
TI  - An estimation of the worldwide economic and health burden of visual impairment.
AB  - This study aims to provide a rigorous estimate of the worldwide costs of visual
      impairment (VI), and the associated health burden. The study used a prevalence
      based model. Prevalence rates for mild VI (visual acuity (VA) worse than 6/12 but
      not worse than 6/18), moderate VI (VA worse than 6/18 but not worse than 6/60)
      and blindness (VA worse than 6/60) were applied to population forecasts for each
      World Health Organisation (WHO) subregion. The limited available country cost
      data were extrapolated between subregions using economic and population health
      indicators. Age and gender subgroup population numbers were derived from United
      Nations' data. Costs and the health burden of VI were estimated for each world
      subregion using published disease prevalence rates, health care expenditures and
      other economic data. The study includes direct health care costs, indirect costs
      and the health burden of VI. The total cost of VI globally was estimated at $3
      trillion in 2010, of which $2.3 trillion was direct health costs. This burden is
      projected to increase by approximately 20% by 2020. VI is associated with a
      considerable disease burden. Unless steps are taken to reduce prevalence through
      prevention and treatment, this burden will increase alongside global population
      growth.

PMID- 22136198
TI  - Effectiveness of biweekly low-dosage peginterferon treatment on the improvement
      of serum alanine aminotransferase and alpha-fetoprotein levels.
AB  - AIM:   The purpose of this clinical study was to determine the effect of a
      biweekly low-dosage peginterferon alpha-2a treatment program on serum alanine
      aminotransferase (ALT) and alpha-fetoprotein (AFP) levels. METHODS:   Fifty-five
      patients participated in the study. The inclusion criteria included chronic
      genotype 1b hepatitis C virus (HCV) infection, liver cirrhosis, or the absence of
      cirrhosis in subjects 65 years old or above, and interferon therapy naivety or a
      lack of sustained response to therapy with interferon-plus-ribavirin or
      peginterferon-plus-ribavirin. Patients were divided into naive, relapser, and non
      responder groups. The median age of the patients was 70 years, and 73% of
      patients had cirrhosis. All patients were treated with peginterferon alpha-2a at
      90 ug biweekly. RESULTS:   The rates of normalization (<=30 IU/l) of ALT levels
      at week 24 in the relapser group and the >=2 log(10)  HCV RNA decline group were
      high (74% and 68%, respectively). However, the ALT and AFP levels decreased
      significantly in each group, including the non-responder group. The ALT levels
      decreased significantly even in patients in whom the HCV RNA levels did not
      decrease. Furthermore, the AFP levels decreased significantly in the patients
      showing no decline in the ALT and HCV RNA levels. Only three patients
      discontinued treatment within 48 weeks due to adverse events, and more than 70%
      of the patients experienced no subjective symptoms during treatment. CONCLUSION: 
      A biweekly low-dosage peginterferon alpha-2a therapy is effective for reducing
      the serum levels of ALT and AFP and may reduce hepatocarcinogenesis in patients
      with liver cirrhosis and in the elderly individuals.

PMID- 22136199
TI  - CT thoracic duct lymphography in cats by popliteal lymph node iohexol injection.
AB  - Three different doses (1.0, 1.5, and 2.0 ml) of iohexol (300 mgl/ml) were
      injected percutaneously into the popliteal lymph node of eight adult cats under
      ultrasound guidance. Serial transverse CT images of five regions of interest (L3,
      T13, T8, T4, and T1 level) were performed at 2-min intervals, and the attenuation
      in Hounsfield Units (HU) of the lymphatic vessels was measured for determination
      of the optimal dose of iohexol and CT scan parameters. The optimal dose was 1.5
      ml and helical CT acquisition is recommended to be performed as soon as possible
      after iohexol injection. In helical scans, the thoracic duct was characterized by
      variable branch numbers that formed a single trunk and entered the venous system
      at variable levels. CT lymphography using this protocol was performed in a cat
      with chylothorax. The thoracic duct was tortuous and focally dilated, and leakage
      of contrast medium was observed. Percutaneous CT lymphography using ultrasound
      guided administration of iohexol into the popliteal lymph node appears reliable
      for delineation of the thoracic duct in cats.

PMID- 22136200
TI  - Central pain contributions in osteoarthritis: next steps for improving
      recognition and treatment?
AB  - There is increasing recognition that central pain sensitivity plays an important
      role in pain severity among patients with osteoarthritis. Murphy and colleagues
      identified clusters of patients with osteoarthritis according to pain severity
      and accompanying symptoms, and one of these groups appeared to have a greater
      degree of centrally mediated pain. This observation provides some evidence that
      patients with greater central pain contributions can be identified in routine
      clinical settings, but brief, evidence-based strategies are still needed to more
      readily and systematically identify these patients. There is also a need to
      develop new strategies and to further evaluate existing therapies
      (pharmacological and nonpharmacological) that target central aspects of
      osteoarthritis pain.

PMID- 22136201
TI  - Direct asymmetric aldol reactions inspired by two types of natural aldolases:
      water-compatible organocatalysts and Zn(II) complexes.
AB  - In this article the utility of water-compatible amino-acid-based catalysts was
      explored in the development of diastereo- and enantioselective direct aldol
      reactions of a broad range of substrates. Chiral C(2)-symmetrical proline- and
      valine-based amides and their Zn(II) complexes were designed for use as efficient
      and flexible chiral catalysts for enantioselective aldol reactions in water, on
      water, and in the presence of water. The presence of 5 mol % of the prolinamide
      based catalyst affords asymmetric intermolecular aldol reactions between
      unmodified ketones and various aldehydes to give anti products with excellent
      enantioselectivities. We also demonstrate aldol reactions of more demanding
      substrates with high affinity to water (i.e., acetone and formaldehyde). Newly
      designed serine-based organocatalyst promoted aldol reaction of hydroxyacetone
      leading to syn-diols. For presented catalytic systems organic solvent-free
      conditions are also acceptable, making the elaborated methodology interesting
      from a green chemistry perspectives.

PMID- 22136203
TI  - Trypanosoma cruzi: in vivo evaluation of iron in skin employing X-ray
      fluorescence (XRF) in mouse strains that differ in their susceptibility to
      infection.
AB  - Trypanosoma cruzi, the causative agent of Chagas' disease (CD), is a substantial
      public health concern in Latin America. Laboratory mice inoculated with T. cruzi
      have served as important animal models of acute CD. Host hypoferremic responses
      occur during T. cruzi infection; therefore, it has been hypothesized that T.
      cruzi requires iron for optimal growth in host cells and, unlike extracellular
      pathogens, may benefit from host hypoferremic responses. Recent technological
      improvements of X-ray fluorescence are useful for diagnostics or monitoring in
      biomedical applications. The goal of our study was to determine whether the iron
      availabilities in Swiss and C57BL/6 mice differ during the acute phase of T.
      cruzi infection and whether the availability correlates with oxidative stress in
      the susceptible and resistant phenotypes identified in these mice. Our results
      showed that the decrease in iron levels in the skin of resistant infected mice
      correlated with the increase in oxidative stress associated with anemia and the
      reduction in parasite burden.

PMID- 22136204
TI  - Efficient n-GaAs photoelectrodes grown by close-spaced vapor transport from a
      solid source.
AB  - n-GaAs films were grown epitaxially on n(+)-GaAs substrates by a close-spaced
      vapor transport method and their photoelectrochemical energy conversion
      properties studied. Under 100 mW cm(-2) of ELH solar simulation, conversion
      efficiencies up to 9.3% for CSVT n-GaAs photoanodes were measured in an
      unoptimized ferrocene/ferrocenium test cell. This value was significantly higher
      than the 5.7% measured for similarly doped commercial n-GaAs wafers. Spectral
      response experiments showed that the higher performance of CSVT n-GaAs films
      relative to the commercial wafers was due to longer minority carrier diffusion
      lengths (L(D)), up to 1,020 nm in the CSVT films compared to 260 nm in the
      commercial n-GaAs wafers. Routes to improve the performance of CSVT GaAs and the
      implications of these results for the development of scalable GaAs-based solar
      energy conversion devices are discussed.

PMID- 22136202
TI  - Gliotransmission modulates baseline mechanical nociception.
AB  - Pain is a physiological and adaptive process which occurs to protect organisms
      from tissue damage and extended injury. Pain sensation beyond injury, however, is
      a pathological process which is poorly understood. Experimental models of
      neuropathic pain demonstrate that reactive astrocytes contribute to reduced
      nociceptive thresholds. Astrocytes release "gliotransmitters" such as D-serine,
      glutamate, and ATP, which is extracellularly hydrolyzed to adenosine. Adenosine 1
      receptor activation in the spinal cord has anti-nociceptive effects on baseline
      pain threshold, but the source of the endogenous ligand (adenosine) in the spinal
      cord is unknown. In this study we used a transgenic mouse model in which SNARE
      mediated gliotransmission was selectively attenuated (called dnSNARE mice) to
      investigate the role of astrocytes in mediating baseline nociception and the
      development of neuropathic pain. Under baseline conditions, immunostaining in the
      dorsal horn of the spinal cord showed astrocyte-specific transgene expression in
      dnSNARE mice, and no difference in expression levels of the astrocyte marker GFAP
      and the microglia marker Iba1 relative to wild-type mice. The Von Frey filament
      test was used to probe sensitivity to baseline mechanical pain thresholds and
      allodynia following the spared nerve injury model of neuropathic pain. DnSNARE
      mice exhibit a reduced nociceptive threshold in response to mechanical
      stimulation compared to wild-type mice under baseline conditions, but nociceptive
      thresholds following spared nerve injury were similar between dnSNARE and wild
      types. This study is the first to provide evidence that gliotransmission
      contributes to basal mechanical nociception.

PMID- 22136205
TI  - Ursolic acid enhances mouse liver regeneration after partial hepatectomy.
AB  - CONTEXT: Ursolic acid is a pentacyclic triterpenoid which has hepatoprotective
      and antihepatotoxic activities. OBJECTIVE: This study investigated whether
      ursolic acid is able to stimulate liver regeneration in partially hepatectomized
      mice. MATERIALS AND METHODS: Ursolic acid or the vehicle solution was orally
      administered to the experimental, sham-operated and vehicle-treated group mice
      for 7 days, positive control animal (mice) was treated with recombinant human
      hepatocyte growth factor (rhHGF), and then the 70% liver partial hepatectomy was
      performed. The liver mass recovery rate was estimated by measuring the ratios of
      mice liver weight to body weight. The liver cells undergoing DNA synthesis were
      identified by immunohistochemistry analysis using monoclonal anti-BrdU
      antibodies. The expression levels of cyclin D1, cyclin E and C/EBP proteins
      (C/EBPalpha and C/EBPbeta) were detected by the Western blotting technique.
      RESULTS: Our results showed administration of ursolic acid significantly
      increased the ratio of the liver to body weight and BrdU labeling index at 36 and
      48 h after partial hepatectomy, and the potency of UA is similar to rhHGF treated
      positive control mice. In addition, ursolic acid treatment significantly
      increased cyclin D1, cyclin E and C/EBPbeta protein expression levels at 36 h
      after liver PHx compared with the vehicle-treated control mice. DISCUSSION AND
      CONCLUSION: All these results suggest that ursolic acid stimulates liver
      proliferation after partial hepatectomy, and this effect may be associated with
      the stimulation of C/EBPbeta expression.

PMID- 22136206
TI  - MicroRNA signature in thyroid fine needle aspiration cytology applied to "atypia
      of undetermined significance" cases.
AB  - BACKGROUND: MicroRNA (miR) expression signatures are proposed to be able to
      differentiate thyroid cancer from benign thyroid lesions. We selected eight miRs
      (miR-146b, -221, -187, -197, -346, -30d, -138, and -302c) to examine the
      potential use of miRs to supplement diagnostic cytology in cases designated as
      "atypia of undetermined significance." METHODS: miR expression was measured in
      thyroid fine needle aspiration (FNA) specimens by quantitative polymerase chain
      reaction. Gene expression analyses and linear discriminant analysis (LDA) were
      performed in a training sample set (n=60) to obtain a classification rule to
      predict FNA cases as benign or malignant. The predictions were cross-validated by
      comparing with the corresponding histological diagnoses. A validation sample set
      (n=68) was further tested with the established four-miR LDA classification rule.
      RESULTS: A set of four miRs (miR-146b, -221, -187, and -30d) was identified that
      could differentiate malignant from benign lesions. A four-miR LDA classification
      rule was obtained and used to predict FNA cases as benign or malignant. For the
      training sample set, we obtained a diagnostic accuracy of 93.3%, sensitivity of
      93.2%, specificity of 93.8%, positive predictive value (PPV) of 0.98, and
      negative predictive value (NPV) of 0.83. For the validation sample set, we
      obtained a diagnostic accuracy of 85.3%, sensitivity of 88.9%, specificity of
      78.3%, PPV of 0.89, and NPV of 0.78. For the 30 atypia cases in the validation
      sample set, we obtained a diagnostic accuracy of 73.3%, sensitivity of 63.6%,
      specificity of 78.9%, PPV of 0.64, and NPV of 0.79. Based on the miR predictions,
      we classified the atypia cases predicted as "malignant" into "high risk" and
      those predicted as "benign" into "low risk" categories. While thyroid carcinomas,
      particularly papillary thyroid carcinomas (PTCs), were relatively enriched in the
      high-risk category, this particular miR panel is subject to inaccurate results in
      follicular neoplasias in atypia cases. CONCLUSIONS: We demonstrate that miR
      amplification from FNA samples is feasible and that the particular four miR
      profile in this study can identify PTCs. However, further refinement is required
      for application to FNA cytology of "atypia of undetermined significance" cases
      due to low accuracy in classifying follicular neoplasias.

PMID- 22136207
TI  - Association of BRCA1 functional single nucleotide polymorphisms with risk of
      differentiated thyroid carcinoma.
AB  - BACKGROUND: Breast cancer 1, early onset (BRCA1) is a vital DNA repair gene, and
      the single nucleotide polymorphisms (SNPs) of this gene have been studied in
      diverse cancer types. In this study, we investigated the association between
      eight common BRCA1 functional SNPs and the risk of differentiated thyroid
      carcinoma (DTC). METHODS: This cancer center-based case-control study included
      303 DTC cases and 511 controls. A polymerase chain reaction-based restriction
      fragment length polymorphism assay was performed for genotyping. Unconditional
      logistical regression analysis was used to calculate odds ratios (ORs) and 95%
      confidence intervals (CIs) in single-SNP analysis and haplotype analysis.
      RESULTS: A decreased risk of DTC was found for the A1988G heterozygous AG
      genotype (adjusted OR=0.63, 95% CI: 0.45-0.87, Bonferroni-adjusted p
      value=0.036). AATAATA and ATAA haplotypes that carry C33420T variant allele were
      associated with reduced papillary thyroid cancer risk (adjusted OR=0.52, 95% CI:
      0.33-0.84; adjusted OR=0.62, 95% CI: 0.40-0.95, respectively). Also, having a
      combination of >=3 favorable genotypes was associated with a DTC risk reduction
      (adjusted OR=0.69, 95% CI: 0.50-0.95). The A31875G AG/GG genotype was associated
      with a 69% reduced risk of multifocal primary tumor in DTC patients (adjusted
      OR=0.31, 95% CI: 0.12-0.81). CONCLUSION: BRCA1 genetic polymorphisms may play a
      role in DTC risk, while the possible associations warrant confirmation in
      independent studies.

PMID- 22136208
TI  - Acute pancreatitis induced by methimazole in a patient with Graves' disease.
AB  - BACKGROUND: Antithyroid drugs such as methimazole (MMI), the mainstay of
      pharmacologic therapy for Graves' disease, can provoke a variety of adverse
      effects. MMI-induced acute pancreatitis is very rare, being described in only a
      few patients and never after more than two exposures as reported here. Here, we
      report an 18-year-old girl with Graves' disease who developed acute pancreatitis
      each time she received MMI. SUMMARY: The patient was an 18-year-old girl with
      Graves' disease who took MMI on four occasions. Each time she promptly developed
      similar features consisting of high fever and left upper quadrant abdominal pain.
      On three occasions, serum lipase and amylase values were measured. Serum lipase
      was elevated on all three occasions and serum amylase was elevated once. Features
      resolved after MMI was stopped. We considered these episodes to be most
      consistent with pancreatitis, and to be induced by MMI administration.
      CONCLUSION: MMI-induced acute pancreatitis is rare and easily misdiagnosed. Based
      on very limited experience, it should resolve after MMI is stopped. The
      pathogenesis of MMI-induced pancreatitis is not known. Clinicians should be aware
      of this entity so that MMI is promptly stopped if the features described here
      develop after MMI is started, and measures are taken to avoid future MMI
      treatment.

PMID- 22136209
TI  - In patients with thyroid cancer of follicular cell origin, a family history of
      nonmedullary thyroid cancer in one first-degree relative is associated with more
      aggressive disease.
AB  - BACKGROUND: About 5% of nonmedullary thyroid cancers (NMTCs) are familial. Most
      patients with a family history of thyroid cancer do not meet the definition of
      familial NMTC (FNMTC; two or more affected family members). The aim of this study
      was to determine whether patients with a family history of NMTC, but who do not
      meet the definition of FNMTC, have more aggressive disease. METHODS: A database
      of 1502 thyroidectomies was reviewed and 358 patients with NMTC who did not have
      a family history of benign thyroid disease and who underwent thyroidectomy from
      January 1994 to December 2008 were identified. These included 324 (90%) patients
      with papillary thyroid carcinoma (PTC), 24 (7%) with follicular thyroid cancer,
      and 10 (3%) with anaplastic or Hurthle cell carcinoma. Among them, those with and
      without a family history of NMTC in first-degree relatives were compared. Then
      patients with only one affected family member were compared with FNMTC patients.
      RESULTS: Thirty-seven (10%) patients had a family history of thyroid cancer, all
      to of which had PTC. Patients with a family history of NMTC had a similar tumor
      size than those without (2+/-0 vs. 2.1+/-0 cm, p=0.72) but they were
      significantly younger (43+/-3 vs. 49+/-1 years, p=0.04), and more likely to have
      multicentricity (48% vs. 22%, p=0.01), malignant lymph nodes (22% vs. 11%,
      p=0.02), and local invasion to surrounding tissues (5.4% vs. 0.6%, p=0.007). They
      also had a higher recurrence rate (24% vs. 12%, p=0.03) than patients without a
      family history. Interestingly, patients with only one affected family member were
      similar to FNMTC patients with respect to age (44+/-4 vs. 40+/-3 years, p=0.4),
      tumor size (2+/-0 vs. 1.9+/-0 cm, p=0.65), rate of multicentricity (44% vs. 52%,
      p=0.57), malignant lymph nodes (22% vs. 21%, p=0.93), local invasiveness (5.5%
      vs. 11%, p=0.59), and disease recurrence (28% vs. 21%, p=0.56). CONCLUSION:
      Patients with NMTC having a family history of thyroid cancer have more aggressive
      disease, regardless of whether they meet the current definition of FNMTC
      regarding number of affected family members. Therefore, any positive family
      history should be considered a risk factor for more aggressive thyroid carcinoma.

PMID- 22136210
TI  - Thyrotoxicosis with post-treatment hypothyroidism in a patient with acute
      suppurative thyroiditis due to porphyromonas.
AB  - BACKGROUND: Acute suppurative thyroiditis (AST) is a rare, life-threatening
      thyroid infection characterized by a tender neck mass and fever. As these
      features are shared with self-limited subacute thyroiditis (SAT), it is important
      to differentiate between the two disorders. PATIENT FINDINGS: We report a case of
      AST in a 21-year-old woman who presented with steadily worsening throat pain for
      3 weeks, a tender left neck mass, and thyrotoxicosis. She was initially given
      prednisone for treatment of presumed SAT but then it acutely worsened. Fine
      needle aspiration yielded pus on gross examination, and she required intubation
      and emergent surgical drainage to maintain her airway. Culture of the abscess
      isolated Streptococcus F and Porphyromonas, a gram-negative intracellular
      anaerobe not previously reported to cause AST. She improved quickly after
      surgery, developed transient hypothyroidism that did not require treatment with
      thyroid hormone, and is currently euthyroid. An abnormal piriform sinus fistula
      was identified on the left using an esophagram. SUMMARY: AST may be difficult to
      clinically differentiate from SAT. Fine needle aspiration revealing pus, culture
      yielding bacteria or fungi, abscess on ultrasonography and computed tomography,
      and left-sided predominance are important in the diagnosis of AST. CONCLUSIONS:
      AST should be considered in any patient with SAT who does not rapidly improve
      following institution of steroids. Further, the presence of thyrotoxicosis does
      not eliminate AST as an initial diagnosis.

PMID- 22136211
TI  - Surgical correction for sinus of valsalva aneurysm with right ventricular outflow
      tract stenosis.
AB  - BACKGROUND: Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly, and SVA
      combined with right ventricular outflow tract stenosis is even rarer. We
      retrospectively analyzed 222 patients receiving surgical repair of SVA in our
      center over nine years, and report the incidence of right ventricular outflow
      tract stenosis in SVAs and the surgical results of 13 cases of SVA with right
      ventricular outflow tract stenosis. METHODS: Between January 2000 and December
      2009, 13 patients with SVA combined with right ventricular outflow tract stenosis
      underwent surgical repair of SVA and correction of right ventricular outflow
      tract stenosis. There were nine males and four females. The mean age was 29.69 +/
      9.98 years (range 13 to 45 years). Associated cardiovascular lesions were
      ventricular septal defect (n = 12), aortic regurgitation (n = 9), mitral
      regurgitation (n = 2), and tricuspid regurgitation (n = 1). All 13 patients were
      followed from 35 to 126 months (mean 80.15 +/- 32,14 months). RESULTS: There was
      neither early death after operation nor late death. All the patients recovered
      well uneventfully. The incidence of right ventricular outflow tract stenosis
      among 222 SVA patients was 5.86%. CONCLUSIONS: Surgical correction of SVA with
      right ventricular outflow tract stenosis results in good mid-term results. Longer
      follow-up is needed to determine the efficacy of this procedure as this cohort of
      patients ages.

PMID- 22136212
TI  - Outpatient treatment of children and adolescents with antidepressants in Croatia.
AB  - OBJECTIVE: This study is aimed to determine the prevalence and patterns of
      antidepressants prescription in outpatient setting in Croatia. METHODS:
      Retrospective analysis of outpatient visits to child psychiatrists by persons
      aged 18 and younger that included prescription of antidepressants during the year
      2010. Antidepressant prescription data were identified by medication class, drug
      entity and were analyzed in relation to age group, gender, psychiatric diagnosis.
      RESULTS: Antidepressants were prescribed to 139 youths (0.240/00), significantly
      more to adolescents than pre-adolescents and for the treatment of depressive
      disorders in females, and mixed disorders of emotions and conduct in males.
      Sertraline was the most prescribed antidepressant for the treatment of major
      depressive disorder, followed by fluvoxamine and tianeptine. Fluvoxamine was the
      most prescribed antidepressant for the treatment of anxiety disorders and mixed
      disorders of emotions and conduct. Off-label prescribing of antidepressants was
      found in 85.6% of young patients. CONCLUSIONS: This study found considerably
      lower prevalence and higher off-label rate of antidepressant prescriptions to
      young people in Croatia to that in other European Countries and in the United
      States. Selective serotonine reuptake inhibitors comprise most of the
      antidepressant medications prescribed to young people, reflecting trends in the
      developed countries.

PMID- 22136213
TI  - Effect of stressful life events on the initiation of graves' disease.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between
      stressful life events (LESs) and its effect on the initiation of Graves' disease
      (GD) and toxic nodular goitre (TNG). PATIENTS AND METHOD: Forty-five patients
      with GD, 24 patients with TNG and 36 healthy control (CG) were included to the
      study. Graves and TNG patients had diagnosed within the last 12 months, with
      clinical and biochemical confirmation in Endocrinology Metabolism Outpatient
      Clinic of Cerrahpasa Medical School. The Holmes-Rahe Stress Scale and the Life
      Experience Survey (LES) was the psychological evaluation instrument used in this
      study. RESULTS: There was no significant difference according to Holmes-Rahe
      scale (Graves & TNG P = 0.329, Graves & Control P = 0.115, TNG and control P =
      0.571). According to LES scale when negative event number, positive event number,
      neutral events and their effects are considered, between Graves and TNG groups no
      statistically difference was observed (P = 0.139, P = 0.083, P = 0.167, P =
      0.162, P = 0.861). The number and impact of negative SLEs were significantly
      higher in GD compared to CG (P = 0.015, P < 0.001). CONCLUSION: According to LES
      scale GD patients has significant difference with respect to CG when negative
      event number and impact are considered.

PMID- 22136214
TI  - Evaluation of anxiety and depression in patients prior to myocardial perfusion
      scintigraphy.
AB  - OBJECTIVE: In myocardial perfusion scintigraphy (MPS) negative results indicate
      coronary artery diseases which might cause prominent anxiety and other
      psychological reactions. The aim of this study was to determine anxiety and
      depression levels of patients prior to MPS procedures. METHODS: The Hospital
      Anxiety Depression Scale(HADS) and the State and Trait Anxiety Inventory I and II
      were used to evaluate the anxiety and depression levels of the patients.
      Descriptive analyses and independent sample t-test were used for statistical
      assessment. RESULTS: The mean score of HADS-anxiety score prior to MPS was 8.1 +/
      4.2, whereas the mean HADS depression score was 6.1 +/- 3.7. The mean state
      anxiety score prior to MPS was 39.7 +/- 10.6 and the mean trait anxiety score was
      45.02 +/- 9.1. HAD and state and trait anxiety scores were found to be
      significantly higher in female patients than male patients and non-smoker
      patients than smoker patients. Other risk factors such as having bypass
      operation, myocardial infarction, hypercholesterolemia, diabetes and hypertension
      were not related to depression and anxiety scores. CONCLUSION: The results in
      this study suggest a role for MPS as a risk factor for higher state anxiety. The
      MPS procedures might lead to an increase in anxiety levels of patients which is
      possibly associated with anticipation anxiety felt during waiting period and
      expectation life-threatening.

PMID- 22136215
TI  - Development of a high-throughput microsphere-based molecular assay to identify 15
      common bloodmeal hosts of Culex mosquitoes.
AB  - For vectorborne infections, host selection by bloodfeeding arthropods dictates
      the interaction between host and pathogen. Because Culex mosquitoes that transmit
      West Nile virus (WNV) feed both on mammalian and avian hosts with varying
      competence, understanding the bloodfeeding patterns of these mosquitoes is
      important for understanding the transmission dynamics of WNV. Herein, we describe
      a new microsphere-based assay using Luminex xMAP(r) technology to rapidly
      identify 15 common hosts of Culex mosquitoes at our California study sites. The
      assay was verified with over 100 known vertebrate species samples and was used in
      conjunction with DNA sequencing to identify over 125 avian and mammalian host
      species from unknown Culex bloodmeals, more quickly and with less expense than
      sequencing alone. In addition, with multiplexed labelled probes, this microsphere
      array identified mixed bloodmeals that were difficult to discern with traditional
      sequencing. The microsphere set was easily expanded or reduced according to host
      range in a specific area, and this assay has made it possible to rapidly screen
      thousands of Culex spp. bloodmeals to extend our understanding of WNV
      transmission patterns.

PMID- 22136216
TI  - Robotic-assisted surgery in the management of endometrial cancer.
AB  - Advanced laparoscopic procedures for hysterectomy and staging lymphadenectomy
      were not widely adopted for management of endometrial cancer despite nearly 20
      years of improvements in laparoscopic technology. Many surgeons have recently
      embraced da Vinci robotic-assisted laparoscopy in preference to traditional
      laparoscopy because of its technological advantages of wristed instrumentation,
      high-definition 3-D optics, ergonomics and autonomy of camera control; the
      majority of women with endometrial cancer in the USA now undergo robotic-assisted
      surgery. The purpose of this article is to review the robotic surgical techniques
      for hysterectomy, pelvic and aortic lymphadenectomy procedures, and the current
      comparative literature discussing perioperative outcomes. Additionally,
      literature that discusses challenges managing obese patients and robotic surgical
      costs are reviewed. Future multi-institutional, prospective registration studies
      comparing perioperative outcomes, complications, pain, recovery time, cost and
      long-term clinical outcomes with open, laparoscopic and robotic procedures will
      be necessary to completely appreciate the impact of robotic-assisted technology.

PMID- 22136217
TI  - Influence of film dimensions on film droplet formation.
AB  - BACKGROUND: Aerosol particles may be generated from rupturing liquid films
      through a droplet formation mechanism. The present work was undertaken with the
      aim to throw some light on the influence of film dimensions on droplet formation
      with possible consequences for exhaled breath aerosol formation. METHODS: The
      film droplet formation process was mimicked by using a purpose-built device,
      where fluid films were spanned across holes of known diameters. As the films
      burst, droplets were formed and the number and size distributions of the
      resulting droplets were determined. RESULTS: No general relation could be found
      between hole diameter and the number of droplets generated per unit surface area
      of fluid film. Averaged over all film sizes, a higher surface tension yielded
      higher concentrations of droplets. Surface tension did not influence the
      resulting droplet diameter, but it was found that smaller films generated smaller
      droplets. CONCLUSIONS: This study shows that small fluid films generate droplets
      as efficiently as large films, and that droplets may well be generated from films
      with diameters below 1 mm. This has implications for the formation of film
      droplets from reopening of closed airways because human terminal bronchioles are
      of similar dimensions. Thus, the results provide support for the earlier proposed
      mechanism where reopening of closed airways is one origin of exhaled particles.

PMID- 22136218
TI  - Comparative analysis of root transcriptome profiles of two pairs of drought
      tolerant and susceptible rice near-isogenic lines under different drought stress.
AB  - BACKGROUND: Plant roots are important organs to uptake soil water and nutrients,
      perceiving and transducing of soil water deficit signals to shoot. The current
      knowledge of drought stress transcriptomes in rice are mostly relying on
      comparative studies of diverse genetic background under drought. A more reliable
      approach is to use near-isogenic lines (NILs) with a common genetic background
      but contrasting levels of resistance to drought stress under initial exposure to
      water deficit. Here, we examined two pairs of NILs in IR64 background with
      contrasting drought tolerance. We obtained gene expression profile in roots of
      rice NILs under different levels of drought stress help to identify genes and
      mechanisms involved in drought stress. RESULTS: Global gene expression analysis
      showed that about 55% of genes differentially expressed in roots of rice in
      response to drought stress treatments. The number of differentially expressed
      genes (DEGs) increased in NILs as the level of water deficits, increased from
      mild to severe condition, suggesting that more genes were affected by increasing
      drought stress. Gene onthology (GO) test and biological pathway analysis
      indicated that activated genes in the drought tolerant NILs IR77298-14-1-2-B-10
      and IR77298-5-6-B-18 were mostly involved in secondary metabolism, amino acid
      metabolism, response to stimulus, defence response, transcription and signal
      transduction, and down-regulated genes were involved in photosynthesis and cell
      wall growth. We also observed gibberellic acid (GA) and auxin crosstalk
      modulating lateral root formation in the tolerant NILs. CONCLUSIONS:
      Transcriptome analysis on two pairs of NILs with a common genetic background
      (~97%) showed distinctive differences in gene expression profiles and could be
      effective to unravel genes involved in drought tolerance. In comparison with the
      moderately tolerant NIL IR77298-5-6-B-18 and other susceptible NILs, the tolerant
      NIL IR77298-14-1-2-B-10 showed a greater number of DEGs for cell growth, hormone
      biosynthesis, cellular transports, amino acid metabolism, signalling,
      transcription factors and carbohydrate metabolism in response to drought stress
      treatments. Thus, different mechanisms are achieving tolerance in the two
      tolerant lines.

PMID- 22136219
TI  - Sensitive biomarkers of cancer recurrence and metastasis: inexpensive tools to
      cut costs and reduce radiation exposure among cancer patients.

PMID- 22136220
TI  - High dietary ratio of omega-6 to omega-3 polyunsaturated acids during pregnancy
      and prevalence of post-partum depression.
AB  - Observational studies suggest association between low concentrations of omega-3
      family fatty acids and greater risk for post-partum depression (PPD). The
      objective was to investigate the effect of unbalanced dietary intake of omega
      6/omega-3 ratio >9:1 in the prevalence for PPD. The study comprises a prospective
      cohort with four waves of follow-up during pregnancy and one following delivery.
      PPD was evaluated according to the Edinburgh Post-partum Depression Scale (PPD >=
      11) in 106 puerperae between 2005 and 2007, in Rio de Janeiro, Brazil.
      Independent variables included socio-demographic, obstetric, pre-pregnancy body
      mass index (BMI) and dietary intake data, which were obtained by means of a food
      frequency questionnaire in the first trimester of pregnancy. Statistical analysis
      involved calculation of PPD prevalence and multivariate Poisson regression with
      robust variance. PPD prevalence amounted to 26.4% [n = 28; confidence interval
      (CI) 95%: 18.0-34.8], and higher prevalences of PPD were observed in women who
      consumed an omega-6/omega-3 ratio >9:1 (60.0%) and in those with pre-pregnancy
      BMI <18.5 kg/m(2) (66.7%). These variables held as factors associated to PPD in
      the multivariate model, elevating the chances of occurrence of the outcome in
      2.50 (CI 95%: 1.21-5.14) and 4.01 times (CI 95%: 1.96-8.20), respectively.
      Analyses were adjusted for age, schooling, pre-pregnancy BMI, lipids consumption
      and time elapsed since delivery. It verified an association between omega-6/omega
      3 ratio above 9:1, the levels recommended by the Institute of Medicine, and the
      prevalence of PPD. These results add to the evidence regarding the importance of
      omega-6 and omega-3 fatty acids in the regulation of mental health mechanisms.

PMID- 22136221
TI  - 'Breast is not always best': South Asian women's experiences of infant feeding in
      the UK within an acculturation framework.
AB  - Acculturating to a host country has a negative impact on immigrant women's
      breastfeeding practices, particularly when coming from countries where
      breastfeeding rates are higher than Western countries. Whether this is true of
      those immigrating to the UK remains to be investigated. The study aimed to
      explore whether acculturating to the UK had detrimental effects on breastfeeding
      practices of South Asian women, and to provide explanations as to how
      acculturation may have exerted its influence. Twenty South Asian women completed
      semi-structured interviews exploring infant feeding experiences. Data were
      thematically analysed. A bidimensional measure assessed women's acculturation
      status. Women displaying low acculturation levels were aware of living in a
      formula-feeding culture but this had little influence on breastfeeding
      intentions/behaviours; drawing upon South Asian cultural teachings of the
      psychological benefits of breast milk. These women opted to formula-feed in
      response to their child's perceived demands or in a bid to resolve conflict;
      either when receiving information about the best feeding method or between their
      roles as a mother and daughter-in-law. Highly acculturated women also experienced
      such conflict; their awareness of the formula-feeding culture governed feeding
      choice. The findings provide a picture of how acculturation may affect South
      Asian women's breastfeeding intentions and behaviours; encouraging health service
      providers to meet the varying needs of an acculturating population. If
      breastfeeding is to be encouraged, it is necessary to understand factors
      influencing feeding choice; with particular attention to the acculturation
      pathways that may govern such decisions. This paper highlights ways to tailor
      information for South Asian women depending on levels of acculturation.

PMID- 22136222
TI  - Using video narratives of women's lived experience of breastfeeding in midwifery
      education: exploring its impact on midwives' attitudes to breastfeeding.
AB  - Strong evidence supports the health benefits of breastfeeding contributing to the
      public health campaign to improve initiation and duration of breastfeeding
      globally, yet breastfeeding continuation rates are persistently low in the UK.
      Inadequate support from health professionals appears to be an underlying feature,
      aggravated by a dearth of professional education that uses a biopsychosocial
      approach. This paper describes how using women's video narratives of their lived
      experience of breastfeeding within higher education impacted positively on the
      attitudes of a group of midwives in relation to supporting breastfeeding women.
      It reports on the qualitative element of a two-phase sequential mixed methods
      study where focus group methods generated rich data about how and why the
      educational intervention altered attitudes. Analysis was thematic. Six major
      themes emerged, 'listening and learning from real women's experiences';
      'generation of emotions'; 'acquisition of new knowledge and learning';
      'reflection on practice'; 'promotion of independent learning' and 'sharing
      learning and ideas with peers'. 'Listening and learning from real women's
      experiences' was central to learning, and was pivotal to attitudinal change,
      motivating an intense need to improve practice. Findings support the value of
      using women's video narratives within midwifery education, through their power to
      integrate affective and cognitive learning, and to promote a transformative
      learning process. This novel approach brings value-added learning benefits by
      enhancing the potential to improve attitudes towards supporting breastfeeding
      women and improving clinical practice.

PMID- 22136223
TI  - Examination of facilitators and barriers to home-based supplemental feeding with
      ready-to-use food for underweight children in western Uganda.
AB  - Poor complementary feeding practices and low-quality complementary foods are
      significant causes of growth faltering and child mortality throughout the
      developing world. Ready-to-use foods (RUF) are energy-dense, lipid-based products
      that do not require cooking or refrigeration that have been used to prevent and
      treat malnutrition among vulnerable children. The effectiveness of these products
      in improving child nutritional status depends on household use by caregivers. To
      identify the key facilitators and barriers that influence appropriate in-home RUF
      consumption by supplemental feeding program beneficiaries, we conducted
      individual interviews among caregivers (n = 80), RUF producers (n = 8) and
      program staff (n = 10) involved in the Byokulia Bisemeye mu Bantu supplemental
      feeding program in Bundibugyo, Uganda. By documenting caregiver perceptions and
      feeding practices related to RUF, we developed a conceptual framework of factors
      that affect appropriate feeding with RUF. Findings suggest that locally produced
      RUF is well received by caregivers and children, and is perceived by caregivers
      and the community to be a healthy supplemental food for malnourished children.
      However, child feeding practices, including sharing of RUF within households,
      compromise the nutrient delivery to the intended child. Interventions and
      educational messages informed by this study can help to improve RUF delivery to
      targeted beneficiaries.

PMID- 22136224
TI  - Re: ESPGHAN's 2008 recommendation for early introduction of complementary foods:
      how good is the evidence? (Cattaneo et al. 2011).

PMID- 22136228
TI  - Empirical classification of eating disorders.
AB  - Current diagnostic criteria for anorexia nervosa (AN) and bulimia nervosa (BN)
      account for a minority of individuals with clinically significant disorders of
      eating, raising concerns about the clinical utility of current definitions. This
      review examines evidence for the validity of current and alternative approaches
      to defining eating disorders and implications for draft criteria for the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
      Although this review largely supports the predictive validity of distinctions
      among AN, BN, and the newly proposed binge eating disorder (BED), it also
      highlights that our tendency to "study what we define" has created a gap between
      the problems that people have and what we know about those problems. Future
      research on the causes and consequences of eating disorders should include more
      heterogeneous groups to enable identification of meaningful boundaries that
      distinguish between disorders based on etiological and predictive validity.

PMID- 22136227
TI  - Improved coiled-coil design enhances interaction with Bcr-Abl and induces
      apoptosis.
AB  - The oncoprotein Bcr-Abl drives aberrant downstream activity through trans
      autophosphorylation of homo-oligomers in chronic myelogenous leukemia (CML).(1,
      2) The formation of Bcr-Abl oligomers is achieved through the coiled-coil domain
      at the N-terminus of Bcr.(3, 4) We have previously reported a modified version of
      this coiled-coil domain, CCmut2, which exhibits disruption of Bcr-Abl oligomeric
      complexes and results in decreased proliferation of CML cells and induction of
      apoptosis.(5) A major contributing factor to these enhanced capabilities is the
      destabilization of the CCmut2 homodimers, increasing the availability to interact
      with and inhibit Bcr-Abl. Here, we included an additional mutation (K39E) that
      could in turn further destabilize the mutant homodimer. Incorporation of this
      modification into CCmut2 (C38A, S41R, L45D, E48R, Q60E) generated what we termed
      CCmut3, and resulted in further improvements in the binding properties with the
      wild-type coiled-coil domain representative of Bcr-Abl [corrected]. A separate
      construct containing one revert mutation, CCmut4, did not demonstrate improved
      oligomeric properties and indicated the importance of the L45D mutation. CCmut3
      demonstrated improved oligomerization via a two-hybrid assay as well as through
      colocalization studies, in addition to showing similar biologic activity as
      CCmut2. The improved binding between CCmut3 and the Bcr-Abl coiled-coil may be
      used to redirect Bcr-Abl to alternative subcellular locations with interesting
      therapeutic implications.

PMID- 22136230
TI  - Dual-parameter optimisation of the elastic properties of skin.
AB  - This paper presents a procedure for characterising the mechanical properties of
      skin using stochastic inverse identification. It is based on the minimisation of
      a cost function relative to the comparison between experimental suction
      experiments and their corresponding finite element models. Two different models
      are compared: a classical single-layer approach and a dual-layer medium which
      account for both the dermis and the hypodermis. Finite element results are used
      to construct the pre-optimisation database which is required for the inverse
      analysis. To compare the calculations, the entire identification is based on a
      dual-parameter optimisation procedure: for the single-layer approach a quadratic
      hyperelastic constitutive equation is used, whereas for the dual-layer medium a
      simple neo-Hookean potential is used. Theoretical conclusions, which are
      developed first, are then compared with actual case studies.

PMID- 22136229
TI  - Genetic variation in TERT and TERC and human leukocyte telomere length and
      longevity: a cross-sectional and longitudinal analysis.
AB  - Telomerase is of key importance for telomere maintenance, and variants of the
      genes encoding its major subunits, telomerase reverse transcriptase (TERT) and
      telomerase RNA component (TERC), are candidates for interindividual variation in
      telomere length. Recently, the two SNPs rs3772190 and rs12696304 in the TERC
      locus were reported to be associated with leukocyte telomere length (LTL) in two
      genome-wide association studies, while one haplotype of TERT (rs2853669,
      rs2736098, rs33954691, and rs2853691) has been reported to be associated with
      both LTL and longevity in a candidate gene study. In this study, we investigated
      the two TERC and four TERT SNPs in middle-aged, old, and oldest-old Danes (58-100
      years) and their association with LTL (n = 864) and longevity (n = 1069).
      Furthermore, data on 11 TERT tagging SNPs in 1089 oldest-old and 736 middle-aged
      Danes were investigated with respect to longevity. For all SNPs, the association
      with longevity was investigated using both a cross-sectional and a longitudinal
      approach. Applying an additive model, we found association of LTL with the minor
      TERC alleles of rs3772190 (A) and rs12696304 (G), such that a shorter LTL was
      seen in rs3772190 A carriers (regression coefficient = -0.08, P = 0.011) and in
      male rs12696304 G carriers (regression coefficient = -0.13, P = 0.014). No TERT
      variations showed association. Moreover, the A allele of rs3772190 (TERC) was
      found to be associated with longevity [hazard rate (AG + AA) = 1.31, P = 0.006].
      No associations with longevity were observed for the TERT SNPs or haplotypes. Our
      study, thus, indicates that TERC is associated with both LTL and longevity in
      humans.

PMID- 22136231
TI  - Mapping N-linked glycosylation sites in the secretome and whole cells of
      Aspergillus niger using hydrazide chemistry and mass spectrometry.
AB  - Protein glycosylation (e.g., N-linked glycosylation) is known to play an
      essential role in both cellular functions and secretory pathways; however, our
      knowledge of in vivo N-glycosylated sites is very limited for the majority of
      fungal organisms including Aspergillus niger. Herein, we present the first
      extensive mapping of N-glycosylated sites in A. niger by applying an optimized
      solid phase glycopeptide enrichment protocol using hydrazide-modified magnetic
      beads. The enrichment protocol was initially optimized using both mouse blood
      plasma and A. niger secretome samples, and it was demonstrated that the protein
      level enrichment protocol offered superior performance over the peptide-level
      protocol. The optimized protocol was then applied to profile N-glycosylated sites
      from both the secretome and whole cell lysates of A. niger. A total of 847 N
      glycosylated sites from 330 N-glycoproteins (156 proteins from the secretome and
      279 proteins from whole cells) were confidently identified by LC-MS/MS. The
      identified N-glycoproteins in the whole cell lysate were primarily localized in
      the plasma membrane, endoplasmic reticulum, Golgi apparatus, lysosome, and
      storage vacuoles, supporting the important role of N-glycosylation in the
      secretory pathways. In addition, these glycoproteins are involved in many
      biological processes including gene regulation, signal transduction, protein
      folding and assembly, protein modification, and carbohydrate metabolism. The
      extensive coverage of N-glycosylated sites and the observation of partial glycan
      occupancy on specific sites in a number of enzymes provide important initial
      information for functional studies of N-linked glycosylation and their
      biotechnological applications in A. niger.

PMID- 22136232
TI  - Lanthanide-thiophene-2,5-dicarboxylate frameworks: ionothermal synthesis, helical
      structures, photoluminescent properties, and single-crystal-to-single-crystal
      guest exchange.
AB  - Eight three-dimensional lanthanide-thiophene-2,5-dicarboxylate frameworks,
      [Ln(TDC)(2)].(choline) (1-6; Ln = Gd, Nd, Eu, Er, Tb, Dy; TDC = thiophene-2,5
      dicarboxylate), [Yb(TDC)(2)(e-urea)].(choline).H(2)O (7; e-urea = ethyleneurea),
      [Nd(2)(TDC)(3)(e-urea)(4)].3(e-urea) (8) have been successfully prepared in deep
      eutectic solvents (choline chloride/e-urea), respectively. Compounds 1-7 are
      anionic frameworks with 8-connected bcu topology, while compound 8 features a
      neutral 6-connected rob-type framework with guest e-urea molecules. In these
      structures, lanthanide ions show dicapped trigonal prism, pentagonal bipyramid,
      and tricapped trigonal prism coordination configurations, respectively, and the
      TDC ligands exhibit different coordination modes. Versatile helical substructures
      are presented in these compounds. The photoluminescent properties of compounds 3
      (Eu) and 8 (Nd) were studied. Moreover, compound 8 can perform single-crystal-to
      single-crystal guest exchange. The ethanol-exchange mechanism of 8 can be
      ascribed to the kinetically controlled flexibility (KCF).

PMID- 22136233
TI  - Biological diversity of fish communities: pattern and process.
AB  - For over 150 years, ecologists have been striving to explain fundamental patterns
      of biological diversity, such as the observation that communities invariably
      consist of common and rare species, and to unravel the processes that underpin
      these patterns. This task is increasingly urgent given the accelerating loss of
      biological diversity. Although fishes are the most diverse vertebrate taxon and
      fish communities occur in a wide range of habitats, they have been relatively
      little studied in the quest to elucidate the processes that shape patterns of
      biological diversity. Here, some of the topics that investigations of fish
      assemblages can illuminate are highlighted. These include the characteristics of
      ecological communities and the role that dispersal limitation plays in
      structuring them, the distinction between core and occasional species, the
      insights that evaluating abundance in different currencies can bring and the
      assessment of community capacity. Questions are identified that future
      investigations of fish communities might tackle and a case study of a biodiverse
      ecoregion (Thailand and Peninsula Malaysia) is used to illustrate the need for
      better links between these ecological questions and effective conservation
      practice.

PMID- 22136234
TI  - Walking the tightrope: trends in African freshwater systematic ichthyology.
AB  - Africa is blessed with an abundance and rich diversity of freshwater fishes,
      reflecting its Gondwanan history and geographical position astride the equator.
      Africa is, however, relatively poorly serviced scientifically, in this respect
      presenting a challenge to the tension between conserving biodiversity and
      sustainable development. Biosystematics has experienced several paradigm shifts
      in the past half century, including the rise of cladistics and more recently the
      adoption of molecular DNA applications to taxonomy and phylogeny and the assembly
      and manipulation of large data sets in an era of major development of
      bioinformatics. The richness of African biodiversity is a magnet to the global
      systematic community that, to a degree, offsets the disadvantage of an
      impoverished indigenous scientific capacity. Conservation biology, however, is
      rooted more closely to the local situation and therefore requires indigenous
      taxonomic services that are inevitably scarce. Balancing this network of tensions
      between scientific knowledge generation and application is like walking a
      tightrope for existing African scientific resources, and to cope it is essential
      to embrace modern innovative approaches such as barcoding to identify organisms.
      This paper considers the historical development of African freshwater
      ichthyology, presents a suite of recent examples illustrating trends in
      systematic ichthyology in Africa and draws conclusions to suggest that both
      traditional and new-age approaches to taxonomy are necessary for a complete
      understanding and appreciation of African freshwater fish diversity and its
      conservation. The chosen examples also suggest that the tensions between the
      approaches can be effectively managed provided exponents work collaboratively.
      The emerging evidence indicates that the combined skills and insight of complex
      scientific teams including systematists, ecologists, molecular biologists and
      earth scientists are needed to resolve the deep complexity of evolution in terms
      of space, time and form.

PMID- 22136235
TI  - Time trends in fish populations in metropolitan France: insights from national
      monitoring data.
AB  - Using the electrofishing database of the French National Agency for Water and
      Aquatic Environment (Onema), the time trends of 48 freshwater fish taxa at 590
      sites monitored for at least 8 years from 1990 to 2009 were investigated. The
      results demonstrated that species richness increased steadily from the beginning
      of the monitoring period. This is congruent with the finding that the number of
      species displaying a significant increase in spatial distribution or abundance
      was greater than those showing a significant decrease. Some species, however, had
      declined both in occurrence and abundance, e.g. tench Tinca tinca, common bream
      Abramis brama, brown trout Salmo trutta and European eel Anguilla anguilla. The
      species showing the most spectacular colonization were non-native, e.g. topmouth
      gudgeon Pseudorasbora parva, wels catfish Silurus glanis and asp Aspius aspius.
      The time trends in population density were related to the maximal body size,
      habitat requirement, occurrence and abundance and the status (i.e. native or
      exotic) but not to the spawning temperature.

PMID- 22136236
TI  - Long-term changes in community composition and life-history traits in a highly
      exploited basin (northern Adriatic Sea): the role of environment and
      anthropogenic pressures.
AB  - The changes in a marine community in the northern Adriatic Sea were explored over
      a period of 65 years using landings data from a commercial fishing fleet, and the
      role of fishing pressure and environmental variations in driving these changes
      was investigated. A total of 40 taxonomic categories, including one or several
      species, were analysed, representing 93.7% of the total landings. From 1945 to
      2010 a significant decrease in the evenness index was observed, indicating a
      trend towards landings dominated by fewer taxa. The composition of the landings
      showed a temporal shift during the 1980s; from 1945 to the 1980s a continuous,
      clear change in composition took place, probably driven by an increase in fishing
      pressure as well as riverine nutrient inputs. Since the 1980s, a different trend
      of changing composition emerged. Among the analysed predictors, fishing capacity,
      summer seawater temperature, inflow from the Po River (the major river of the
      northern Adriatic Sea) and nutrients were related to the changes in landings. In
      relation to life-history traits of the landed species, the community shifted from
      large, late-maturing species to more fecund, smaller and earlier-maturing
      species. A high fishing pressure is probably the major cause of these changes,
      possibly acting synergistically with environmental variations.

PMID- 22136237
TI  - Asian river fishes in the Anthropocene: threats and conservation challenges in an
      era of rapid environmental change.
AB  - This review compares and contrasts the environmental changes that have
      influenced, or will influence, fishes and fisheries in the Yangtze and Mekong
      Rivers. These two rivers have been chosen because they differ markedly in the
      type and intensity of prevailing threats. The Mekong is relatively pristine,
      whereas the Three Gorges Dam on the Yangtze is the world's largest dam
      representing the apotheosis of environmental alteration of Asian rivers thus far.
      Moreover, it is situated at the foot of a planned cascade of at least 12 new dams
      on the upper Yangtze. Anthropogenic effects of dams and pollution of Yangtze
      fishes will be exacerbated by plans to divert water northwards along three
      transfer routes, in part to supplement the flow of the Yellow River. Adaptation
      to climate change will undoubtedly stimulate more dam construction and flow
      regulation, potentially causing perfect storm conditions for fishes in the
      Yangtze. China has already built dams along the upper course of the Mekong, and
      there are plans for as many as 11 mainstream dams in People's Democratic Republic
      (Laos) and Cambodia in the lower Mekong Basin. If built, they could have profound
      consequences for biodiversity, fisheries and human livelihoods, and such concerns
      have stalled dam construction. Potential effects of dams proposed for other
      rivers (such as Nujiang-Salween) are also cause for concern. Conservation or
      restoration measures to sustain some semblance of the rich fish biodiversity of
      Asian rivers can be identified, but their implementation may prove problematic in
      a context of increasing Anthropocene alteration of these ecosystems.

PMID- 22136238
TI  - Fish response to the temporal hierarchy of the natural flow regime in the Daly
      River, northern Australia.
AB  - In this study, relationships between flow variation across multiple temporal
      scales and the distribution and abundance of three fish species, western
      rainbowfish Melanotaenia australis, sooty grunter Hephaestus fuliginosus and
      barramundi Lates calcarifer were examined at eight sampling reaches in the Daly
      River, Northern Territory, Australia. Discharge was highly seasonal during the
      study period of 2006-2010 with a distinct wet-dry discharge pattern. Significant
      catchment-wide correlations were identified between species abundance and
      hydrologic variables across several scales describing the magnitude and
      variability of flow. A Bayesian hierarchical model which accounted for >80% of
      variation in abundances for all species and age classes (i.e. juvenile and
      adult), identified the extent to which the influence of short-term flow variation
      was dependent upon the historical flow regime. There were distinct ontogenetic
      differences in these relationships for H. fuliginosus, with variability of recent
      flows having a negative effect on juveniles which was stronger at locations with
      higher historical mean daily flow. Lates calcarifer also displayed ontogenetic
      differences in relationships to flow variation with adults showing a positive
      association with increase in recent flows and juveniles showing a negative one.
      The effect of increased magnitude of wet-season flows on M. australis was
      negative in locations with lower historical mean daily flow but positive in
      locations with higher historical mean daily flow. The results highlighted how
      interactions between multiple scales of flow variability influence the abundance
      of fish species according to their life-history requirements.

PMID- 22136239
TI  - Out of sight out of mind: current knowledge of Chinese cave fishes.
AB  - Caves and karsts are among the most threatened ecosystems in the world. They are
      very fragile, balanced habitats with high levels of endemic species that are
      extremely sensitive to environmental changes. In recent decades, however, threats
      from rapid economic growth have increased the need for conservation efforts for
      cave-dwelling communities. In addition, difficulties in accessing and sampling
      these habitats mean that they remain as one of the least known ecosystems in the
      world with modern studies of cave fishes only starting in China during the 1980s.
      Here, the current status of cave fishes in China is reviewed. China is host to
      the highest number of cave fish species in the world, with 48 troglobite species
      out of a total of 101 cave fish species. All of these cave fish species (one
      order and three families) and half of the genera are endemic to China with
      Sinocyclocheilus being the most speciose cave fish genus. Species from this genus
      possess horns and humpbacks resulting from processes of parallel evolution, but
      the function of these features remains unknown. With the exception of Onychostoma
      macrolepis distributed in north China, all other species are found in the karst
      environment of the Yunnan-Guizhou Plateau. Sympatric distribution is common, and
      sometimes several different cave fish species can be found in the same cave or
      subterranean river. For this reason, Chinese cave fishes represent an important
      evolutionary framework.

PMID- 22136240
TI  - Communication gaps in knowledge of freshwater fish biodiversity: implications for
      the management and conservation of Mexican biosphere reserves.
AB  - To detect differences in the information available on freshwater fish species
      found in Mexican biosphere reserves, the number of species considered in three
      sources of information: management programmes, Global Biodiversity Information
      Facility (GBIF) and the scientific literature were compared. Additionally,
      management actions for the reserves were evaluated. More than 55% of freshwater
      fish species registered for the reserves were found only in one of the three
      sources of information, while just 12% was shared among all the three. Fifteen
      threatened species were registered in GBIF and the scientific literature that
      were not found in management programmes. Although all the management programmes
      described conservation actions, none of them gave details about how they would be
      implemented. Lack of communication among the sources studied, unawareness of the
      existence of threatened species and the absence of detailed management actions
      hinder the development of adequate conservation strategies.

PMID- 22136241
TI  - Heated competition: how climate change will affect non-native pumpkinseed Lepomis
      gibbosus and native perch Perca fluviatilis interactions in the U.K.
AB  - Heated and ambient temperature experimental ponds were used to examine
      competition between introduced pumpkinseed Lepomis gibbosus and native perch
      Perca fluviatilis in England, U.K., and how these interactions are likely to
      change under climate warming conditions. Results from three sets of two-week
      experiments indicated that in both species and in all sets, growth was faster in
      heated than in ambient temperature ponds. Growth of both P. fluviatilis and L.
      gibbosus in sympatry did not differ significantly from that observed in
      allopatric ponds. Diet analysis indicated that increased resource partitioning
      occurred when P. fluviatilis and L. gibbosus were reared in sympatry, with P.
      fluviatilis shifting to a diet higher in microcrustaceans. The results do not
      support the previous claims of adverse effects of L. gibbosus on P. fluviatilis
      populations. Under conditions of climate change, however, which have been
      demonstrated experimentally to enhance L. gibbosus recruitment, this species is
      expected to become invasive in England, resulting in higher densities that may
      exert a stronger competitive effect than examined in this study.

PMID- 22136242
TI  - Towards the conservation of crucian carp Carassius carassius: understanding the
      extent and causes of decline within part of its native English range.
AB  - The extent and causes of crucian carp Carassius carassius decline were assessed
      during an initial study of c. 25 ponds in north Norfolk, eastern England, U.K.,
      which was then replicated (a validation study) on another c. 25 ponds in an
      adjacent area. Of these ponds, c. 40 are known to have contained C. carassius
      during the 1970s-1980s. In the initial and validation studies, C. carassius were
      found in only 11 of these ponds, yielding declines of 76% (five of 21 ponds) and
      68% (six of 19 ponds), respectively (72% decline overall). Non-native cyprinids,
      including goldfish Carassius auratus and common carp Cyprinus carpio and their
      hybrids with C. carassius, were observed in 20% of the ponds. Causes of C.
      carassius local extinction from 21 ponds were confidently determined as
      desiccation due to drought, terrestrialization and habitat deterioration,
      hybridization and competition with non-native cyprinids, agricultural land
      reclamation and predation (after the introduction of pike Esox lucius). This
      study led to C. carassius being designated as a Biodiversity Action Plan (BAP)
      species in the county of Norfolk, the first formal conservation designation for
      the species in the U.K. The C. carassius BAP plan aims to halt the decline of
      this much overlooked species through reintroductions and selective stocking of
      suitable ponds within the native range of the species.

PMID- 22136243
TI  - Small-scale Arctic charr Salvelinus alpinus fisheries in Canada's Nunavut:
      management challenges and options.
AB  - The Arctic charr Salvelinus alpinus is a diverse and abundant resource in
      Canada's Nunavut. The anadromous form is primarily targeted by exploitation in
      small-scale fisheries. The continued importance of subsistence fisheries and
      growing interest in further developing commercial fisheries underline the need
      for proper management of S. alpinus in northern Canada. This paper presents the
      current state of S. alpinus fisheries in Nunavut and related management
      challenges. An alternate framework for assessment using life-history information
      as it determines stock productivity and resilience to harvesting is presented.
      This framework combines (1) a risk assessment tool [productivity-susceptibility
      analysis (PSA)] to evaluate the relative vulnerability of S. alpinus stocks to
      harvest and (2) a conceptual model for quantitative assessment to determine
      sustainable harvest levels. Diversity in S. alpinus life history and contrast in
      vulnerability scores derived from PSA assessment are demonstrated for a sample of
      86 anadromous stocks from throughout Nunavut. These data provide evidence in
      support of an alternate strategy for assessment permitting to integrate diversity
      in S. alpinus life history for improved generalization and representativeness.
      Salvelinus alpinus fisheries in Arctic regions exemplify the need for stock
      assessment and management alternatives to ensure fish conservation in remote,
      sensitive ecosystems and in data-poor circumstances.

PMID- 22136244
TI  - Importance of fish behaviour in modelling conservation problems: food limitation
      as an example.
AB  - Simulation experiments using the inSTREAM individual-based brown trout Salmo
      trutta population model explored the role of individual adaptive behaviour in
      food limitation, as an example of how behaviour can affect managers'
      understanding of conservation problems. The model includes many natural
      complexities in habitat (spatial and temporal variation in characteristics such
      as depth and velocity, temperature, hiding and feeding cover, drift-food supply
      and predation risk), fish physiology (especially, how food intake and growth vary
      with hydrodynamics, cover, fish size and temperature) and behaviour. When drift
      food concentration was increased over a wide range in 7 year simulations, the
      simulated population was always food limited. In fact, as food supply increased,
      the population increased at an increasing rate and consumed a higher percentage
      of the food supply, apparently because higher food concentrations make more
      stream area energetically profitable for drift feeders. The behaviour most
      responsible for this response was activity selection: when food was abundant,
      fish chose to feed less frequently and more nocturnally, thereby reducing
      predation mortality so more fish survived longer. These results indicate that the
      traditional concept of food limitation, that food availability stops limiting
      population size when it exceeds some threshold level, may not be useful and can
      be misleading. Results also strongly contradict the concept that a salmonid
      population is not food limited if the total food supply is greater than the
      population's consumption. Explicit consideration of adaptive behaviour produced a
      novel but believable understanding of food effects on salmonid populations.
      Published 2011. This article is a U.S. Government work and is in the public
      domain in the USA.

PMID- 22136245
TI  - Paradigm shifts in fish conservation: moving to the ecosystem services concept.
AB  - Various factors constrain the existence and development of inland fishes and
      fisheries, such as pollution, habitat degradation, alien invasive species, local
      user conflicts, low social priority and inadequate research and funding. In many
      cases, however, degradation of the environment and loss of aquatic habitat are
      the predominant concerns for the conservation of freshwater aquatic biota. The
      need for concerted effort to prevent and reduce environmental degradation, as
      well as protection of freshwater fishes and fisheries as renewable common pool
      resources or entities in their own right, are the greatest challenges facing the
      conservation of fishes in inland waters. Unfortunately, traditional conservation
      practices such as regulation of exploitation, protected areas and habitat
      restoration have failed to arrest the alarming increase in number of threatened
      freshwater fish species worldwide. This paper examines the shifting paradigm of
      fisheries management from rule-based regulation, through fishery enhancement
      towards the ecosystem approach to fisheries, with reference to inland waters, and
      how the emerging concept of ecosystem services coupled with traditional fish
      conservation management practices, institutional restructuring and integrated
      management planning should provide a more sustainable thrust to formulation and
      promotion of fish conservation initiatives.

PMID- 22136246
TI  - T cells as key players for bone destruction in gouty arthritis?
AB  - The deposition of monosodium urate (MSU) crystals in synovial fluid and tissue
      leads to gouty arthritis frequently associated with synovial inflammation and
      bone erosions. The cellular mechanism that links MSU crystals to an increased
      number of osteoclasts has not yet been fully understood. In a recent issue of
      Arthritis Research & Therapy Lee and colleagues proposed that bone destruction in
      chronic gouty arthritis is at least in part dependent on expression by T cells of
      receptor activator of NF-kappaB ligand (RANKL). The authors showed that pro
      resorptive cytokines such as IL-1beta, IL-6, and TNFalpha are expressed within
      tophi and stromal infiltrates. In vitro stimulation with MSU crystals revealed
      monocytes as a source for these cytokines, whereas T cells produce RANKL, the
      major trigger of osteoclastogenesis.

PMID- 22136247
TI  - Ecological transcriptomics of lake-type and riverine sockeye salmon (Oncorhynchus
      nerka).
AB  - BACKGROUND: There are a growing number of genomes sequenced with tentative
      functions assigned to a large proportion of the individual genes. Model organisms
      in laboratory settings form the basis for the assignment of gene function, and
      the ecological context of gene function is lacking. This work addresses this
      shortcoming by investigating expressed genes of sockeye salmon (Oncorhynchus
      nerka) muscle tissue. We compared morphology and gene expression in natural
      juvenile sockeye populations related to river and lake habitats. Based on
      previously documented divergent morphology, feeding strategy, and predation in
      association with these distinct environments, we expect that burst swimming is
      favored in riverine population and continuous swimming is favored in lake-type
      population. In turn we predict that morphology and expressed genes promote burst
      swimming in riverine sockeye and continuous swimming in lake-type sockeye.
      RESULTS: We found the riverine sockeye population had deep, robust bodies and
      lake-type had shallow, streamlined bodies. Gene expression patterns were measured
      using a 16 k microarray, discovering 141 genes with significant differential
      expression. Overall, the identity and function of these genes was consistent with
      our hypothesis. In addition, Gene Ontology (GO) enrichment analyses with a larger
      set of differentially expressed genes found the "biosynthesis" category enriched
      for the riverine population and the "metabolism" category enriched for the lake
      type population. CONCLUSIONS: This study provides a framework for understanding
      sockeye life history from a transcriptomic perspective and a starting point for
      more extensive, targeted studies determining the ecological context of genes.

PMID- 22136248
TI  - Infrared study of the stability and folding kinetics of a series of beta-hairpin
      peptides with a common NPDG turn.
AB  - The thermal stability and folding kinetics of a series of 15-residue beta
      hairpins with a common Type I [3:5] NPDG turn were studied using Fourier
      transform infrared spectroscopy (FTIR) and laser-induced temperature jump (T
      jump) with infrared detection, respectively. Mutations at positions 3, 5, or 13
      in the peptide sequence SEXYXNPDGTWTXTE, where X represents the position of
      mutation, were performed to study the roles of hydrophobic interactions in
      determining the thermodynamic and kinetic properties of beta-hairpin folding. The
      thermal stability studies show a broad thermal folding/unfolding transition for
      all the peptides. T-jump studies indicate that these beta-hairpin peptides fold
      in less than 2 MUs. In addition, both folding and unfolding rate constants
      decrease with increasing strength of hydrophobic interactions. Kinetically, the
      hydrophobic interactions have more significant influence on the unfolding rate
      than the folding rate. Phi-value analysis indicates that the hydrophobic
      interactions between the side chains are mainly formed at the latter part of the
      transition-state region during the folding process. In summary, the results
      suggest that the formation of the native structure of these beta-hairpins depends
      on the correct topology of the hydrophobic cluster. Besides the formation of the
      turn region as a key process for folding as suggested by previous studies, a
      hydrophobic collapse process may also play a crucial role during beta-hairpin
      folding.

PMID- 22136249
TI  - Expression levels of mRNA-encoding PDGF receptors in goat ovaries and the
      influence of PDGF on the in vitro development of caprine pre-antral follicles.
AB  - The aims of this study were to investigate the expression levels of mRNA for
      platelet-derived growth factor (PDGF) receptors (PDGFR-alpha and -beta) in
      caprine follicles at different developmental stages and to evaluate the influence
      of PDGF on the in vitro development of pre-antral follicles. For this, goat
      primordial, primary and secondary follicles, as well as small (1-3 mm) and large
      (3-6 mm) antral follicles, were obtained, and PDGFR-alpha and -beta mRNA levels
      were quantified by real-time PCR. Furthermore, pre-antral follicles (>= 200 MUm)
      were isolated from goat ovaries and cultured for 18 days in alpha- minimum
      essential medium supplemented with PDGF at 50 or 100 ng/ml, containing or not
      FSH. Real-time PCR showed highest PDGFR-alpha mRNA levels in secondary follicles,
      while PDGFR-beta mRNA levels were highest in primary follicles onwards. Both
      receptors showed higher mRNA levels in granulosa/theca cells from small and large
      antral follicles than in their corresponding cumulus-oocyte complexes. In
      culture, the percentage of antrum formation was significantly higher in 100 ng/ml
      PDGF compared with the same PDGF concentration associated with FSH. After 18
      days, PDGF in both concentrations associated with FSH promoted follicular growth
      significantly higher than the control. Moreover, the addition of FSH to 50 ng/ml
      PDGF positively influenced the follicular growth when compared with the same PDGF
      concentration in the absence of FSH. In conclusion, PDGF is important for early
      goat folliculogenesis, because the presence of PDGFR-alpha and -beta mRNA was
      detected in all follicular categories, and PDGF associated with FSH stimulated
      the growth of goat pre-antral follicles isolated and cultured in vitro.

PMID- 22136250
TI  - One-pot access to indolo[2,3-b]quinolines by electrophile-triggered cross
      amination/Friedel-Crafts alkylation of indoles with 1-(2
      tosylaminophenyl)ketones.
AB  - Activation of C2 and C3 of indoles by molecular iodine (I(2)) and base followed
      by in situ reaction with 1-(2-tosylaminophenyl)ketones or 2
      tosylaminobenzaldehyde can afford highly substituted indolo(2,3-b)quinolines in
      moderate to excellent yields (up to 99%). The reaction provides a metal-free
      selective difunctionalization of indoles. The synthetic potential of the protocol
      has been illustrated by the synthesis of neocryptolepine and its 11-methyl
      analogue.

PMID- 22136252
TI  - Single-composition trichromatic white-emitting Ca4Y6(SiO4)6O: Ce3+/Mn2+/Tb3+
      phosphor: luminescence and energy transfer.
AB  - A series of Ca(4)Y(6)(SiO(4))(6)O (CYS): Ce(3+)/Mn(2+)/Tb(3+) oxyapatite
      phosphors were prepared via high-temperature solid-state reaction. Under UV
      excitation, there exist dual energy transfers (ET), i.e., Ce(3+)->Mn(2+) and
      Ce(3+)->Tb(3+) in the CYS: Ce(3+), Mn(2+), Tb(3+) system and their emitting
      colors can be adjusted from blue to orange-red via ET of Ce(3+)->Mn(2+) and from
      blue to green via ET of Ce(3+)->Tb(3+), respectively. Moreover, a wide-range
      tunable white light emission with high quantum yields (13%-30%) were obtained by
      precisely controlling the contents of Ce(3+), Mn(2+) and Tb(3+) ions. On the
      other hand, the CL properties of CYS: Ce(3+), Mn(2+), Tb(3+) phosphors have been
      investigated in detail. The studied results indicate that the as-prepared CYS:
      Ce(3+), Mn(2+), Tb(3+) phosphors have good CL intensity and CIE color coordinate
      stability with a color-tunable emission crossing the whole white light region
      under low-voltage electron beam excitation. In general, the white light with
      varied hues has been obtained in Ce(3+), Mn(2+), and Tb(3+)-triactivated CYS
      phosphors by utilizing the principle of energy transfer and properly designed
      activator contents under UV (284, 358 nm) and low-voltage (1-5 kV) electron beam
      excitation, which make them as a potential single-composition trichromatic white
      emitting phosphor.

PMID- 22136251
TI  - Analogues of orphan nuclear receptor small heterodimer partner ligand and
      apoptosis inducer (E)-4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid.
      2. Impact of 3-chloro group replacement on inhibition of proliferation and
      induction of apoptosis of leukemia and cancer cell lines.
AB  - The parent phenol of adapalene and its (E)-cinnamic acid analogue were found to
      induce cancer cell apoptosis but cause adverse systemic effects when administered
      to mice. In contrast, their respective 5-Cl- and 3-Cl-substituted analogues had
      their adverse effects mitigated without a comparable loss of cancer cell
      inhibitory activity. As a result, pharmacologic space in this region of the
      cinnamic phenyl ring scaffold was explored. Various substituents were introduced,
      and their effects on cancer cell proliferation and viability were evaluated.
      Cinnamic acids having 3-Br, CN, NO(2), NH(2), OMe, and N(3) groups had activity
      comparable to that of 4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-chlorocinnamic
      acid. A comparative molecular field analysis study indicated that introduction of
      an H-bond acceptor at position 3 of the central phenyl ring would favor
      inhibition of leukemia cell viability, and docking suggested its hydrogen bonding
      with a polar group in a small heterodimer partner homology model. The 3-CN,
      NO(2), NH(2), and OH analogues also inhibited MMTV-Wnt1 murine mammary stem cell
      viability.

PMID- 22136255
TI  - Forthcoming events.

PMID- 22136253
TI  - Revelation on the potency of alpha(1) -blockers - parallel blockade of
      angiotensin II receptor: a new finding.
AB  - CONTEXT: The problem of hypertension has gained enormous proportions in the past
      decade. Multifactorial etiology and complex pathophysiology of the disease has
      rendered the treatment of the disease a hard task. Sympathetic nervous system and
      the renin-angiotensin-aldosterone system are primary contributors of blood
      pressure homeostasis. OBJECTIVE: Structural similarities were identified among
      AT(1) and alpha(1)-antagonists, initiating a speculation that alpha(1)
      antagonists could possibly block the AT(1) receptor and vice-versa. METHODS: To
      corroborate this speculation, we screened prototypical alpha(1)-antagonists such
      as prazosin, doxazosin, and terazosin for antagonism of angiotensin II on rat
      aortic strips. We also examined the AT(1) antagonists losartan, valsartan, and
      olmesartan for their possible antagonistic effect, on contractions of rat aortic
      strips induced by phenylephrine. RESULTS: To our astonishment, we found that
      prazosin and its analogs which have been reported to have alpha(1)-antagonistic
      activity only, were able to shift concentration response curves of angiotensin
      II. CONCLUSION: Our findings suggest that the potent antihypertensive effect of
      prazosin-type alpha(1)-antagonists is not purely due to alpha(1)-receptor
      blocking activity of these compounds but also due to blockade of AT(1) receptors.
      This finding may lead to the development of more potent dual inhibitors which
      would prove to be of immense value in the control of the scourge of hypertension.

PMID- 22136256
TI  - Transcription factor binding sites are highly enriched within microRNA precursor
      sequences.
AB  - BACKGROUND: Transcription factors are thought to regulate the transcription of
      microRNA genes in a manner similar to that of protein-coding genes; that is, by
      binding to conventional transcription factor binding site DNA sequences located
      in or near promoter regions that lie upstream of the microRNA genes. However, in
      the course of analyzing the genomics of human microRNA genes, we noticed that
      annotated transcription factor binding sites commonly lie within 70- to 110-nt
      long microRNA small hairpin precursor sequences. RESULTS: We report that about
      45% of all human small hairpin microRNA (pre-miR) sequences contain at least one
      predicted transcription factor binding site motif that is conserved across human,
      mouse and rat, and this rises to over 75% if one excludes primate-specific pre
      miRs. The association is robust and has extremely strong statistical
      significance; it affects both intergenic and intronic pre-miRs and both isolated
      and clustered microRNA genes. We also confirmed and extended this finding using a
      separate analysis that examined all human pre-miR sequences regardless of
      conservation across species. CONCLUSIONS: The transcription factor binding sites
      localized within small hairpin microRNA precursor sequences may possibly regulate
      their transcription. Transcription factors may also possibly bind directly to
      nascent primary microRNA gene transcripts or small hairpin microRNA precursors
      and regulate their processing.

PMID- 22136257
TI  - Applying plant DNA barcodes to identify species of Parnassia (Parnassiaceae).
AB  - DNA barcoding is a technique to identify species by using standardized DNA
      sequences. In this study, a total of 105 samples, representing 30 Parnassia
      species, were collected to test the effectiveness of four proposed DNA barcodes
      (rbcL, matK, trnH-psbA and ITS) for species identification. Our results
      demonstrated that all four candidate DNA markers have a maximum level of primer
      universality and sequencing success. As a single DNA marker, the ITS region
      provided the highest species resolution with 86.7%, followed by trnH-psbA with
      73.3%. The combination of the core barcode regions, matK+rbcL, gave the lowest
      species identification success (63.3%) among any combination of multiple markers
      and was found unsuitable as DNA barcode for Parnassia. The combination of
      ITS+trnH-psbA achieved the highest species discrimination with 90.0% resolution
      (27 of 30 sampled species), equal to the four-marker combination and higher than
      any two or three marker combination including rbcL or matK. Therefore, matK and
      rbcL should not be used as DNA barcodes for the species identification of
      Parnassia. Based on the overall performance, the combination of ITS+trnH-psbA is
      proposed as the most suitable DNA barcode for identifying Parnassia species. DNA
      barcoding is a useful technique and provides a reliable and effective mean for
      the discrimination of Parnassia species, and in combination with morphology-based
      taxonomy, will be a robust approach for tackling taxonomically complex groups. In
      the light of our findings, we found among the three species not identified a
      possible cryptic speciation event in Parnassia.

PMID- 22136258
TI  - Endovascular repair of thoracic aortoenteric fistulas.
AB  - Aortoesophageal fistula is a rare manifestation of thoracic aortic surgery or
      esophageal disease. We describe a patient who underwent emergent endovascular
      repair of an aortoesophageal fistula due to a ruptured penetrating ulcer of the
      descending thoracic aorta and review the literature on this subject.

PMID- 22136259
TI  - Controlled release pulmonary administration of curcumin using swellable
      biocompatible microparticles.
AB  - This study involves a promising approach to achieve sustained pulmonary drug
      delivery. Dry powder particulate carriers were engineered to allow simultaneous
      aerosol lung delivery, evasion of macrophage uptake, and sustained drug release
      through a controlled polymeric architecture. Chitosan grafted with PEG was
      synthesized and characterized (FTIR, EA, DSC and 2D-XRD). Then, a series of
      respirable amphiphilic hydrogel microparticles were developed via spray drying of
      curcumin-loaded PLGA nanoparticles with chitosan-grafted-PEG or chitosan. The
      nanoparticles and microparticles were fully characterized using an array of
      physicochemical analytical methods including particle size, surface morphology,
      dynamic swelling, density, moisture content and biodegradation rates. The PLGA
      nanoparticles and the hydrogel microspheres encapsulating the curcumin-loaded
      PLGA nanoparticles showed average size of 221-243 nm and 3.1-3.9 MUm,
      respectively. The developed carriers attained high swelling within a few minutes
      and showed low moisture content as dry powders (0.9-1.8%), desirable
      biodegradation rates, high drug loading (up to 97%), and good sustained release.
      An aerosolization study was conducted using a next generation impactor, and
      promising aerosolization characteristics were shown. In vitro macrophage uptake
      studies, cytotoxicity and in vitro TNF-alpha assays were performed for the
      investigated particles. These assays revealed promising biointeractions for the
      respirable/swellable nano-micro particles developed in this study as potential
      carriers for sustained pulmonary drug delivery.

PMID- 22136260
TI  - Cosmetic surgery prior to diagnosis of breast cancer.
AB  - BACKGROUND: Cosmetic breast surgery is amongst the top five most commonly
      performed cosmetic surgical procedures. With breast cancer being the most common
      non-skin malignancy in women, the likelihood that a woman undergoing cosmetic
      breast surgery may have an occult breast cancer needs to be considered. Most of
      the available data pertaining to breast cancer diagnosis in the setting of
      cosmetic surgery are from studies of cosmetic breast surgery populations. We
      report on the prevalence of breast cancer as an incidental finding during
      cosmetic breast surgery in the context of women subsequently diagnosed with
      invasive breast cancer. METHODS: The Bupa Health Foundation Health and Wellbeing
      after Breast Cancer Study is a prospective cohort study of 1684 women recruited
      within 12 months of their first diagnosis with invasive breast cancer.
      Participants completed an enrolment questionnaire and annual follow-up
      questionnaires for 5 years. RESULTS: At the second follow-up, 1.5% of women
      reported having undergone cosmetic breast surgery prior to being diagnosed with
      breast cancer, 16 had undergone breast reduction and seven had augmentations.
      Invasive breast cancer was diagnosed at the time of a cosmetic breast procedure
      in two women, in both an augmentation and a reduction procedure, which is 8.7%
      (95% confidence interval 23.5% to +20.9%) of the women in our study reporting a
      cosmetic breast procedure prior to diagnosis. CONCLUSIONS: Although prior
      cosmetic breast surgery was reported by few women, breast cancer was diagnosed in
      two women during the procedure. Surgeons performing elective breast surgery need
      to understand and apply consistent, reliable breast cancer screening practices.

PMID- 22136261
TI  - Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into
      foods from the Indian subcontinent - a blinded, randomised, placebo controlled
      trial.
AB  - BACKGROUND: Coronary heart disease (CHD) is highly prevalent amongst the South
      Asian communities in Britain. The reasons for this excess CHD risk are
      multifactorial, but in part relate to a susceptibility to diabetes mellitus -
      where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose
      are likely to underpin vascular disease in this population. Dietary intervention
      is an important and first line approach to manage increased CHD risk. However,
      there is limited information on the impact of the South Asian diet on CHD risk.
      METHODS/DESIGN: The Diabetes Health, Residence & Metabolism in Asians (DHRMA)
      study is a blinded, randomised, placebo controlled trial that analyses the
      efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in
      relation to cardio-metabolic risk factors that are commonly perturbed amongst
      South Asian populations - primarily glucose, fatty acid and lipoprotein
      metabolism and central adiposity. Using a 10-week dietary intervention study, 50
      healthy South Asians will be randomised to receive either a DHRMA (reduced GI)
      supply of chapatti (bread), stone ground, high protein wheat flour and white
      basmati rice (high bran, unpolished) or commercially available (leading brand)
      versions chapatti wheat flour and basmati rice. Volunteers will be asked to
      complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up,
      where blood metabolites and hormones, blood pressure and anthropometry will also
      be assessed in a standardised manner. DISCUSSION: It is anticipated that the
      information collected from this study help develop healthy diet options specific
      (but not exclusive) for South Asian ethnic communities. Trial registration
      Current Controlled Trials ISRCTN02839188.

PMID- 22136262
TI  - Emergency medicine physicians' perspectives of providing palliative care in an
      emergency department.
AB  - This study describes emergency physicians' perspectives on the challenges and
      benefits to providing palliative care in an academic, urban, public hospital in
      Los Angeles. Participants underwent a semi-structured interview on their training
      and experiences related to palliative care, perceptions of providing palliative
      care, and their recommendations for education and training in this area. Overall,
      respondents felt that palliative care is not prioritized appropriately, leading
      patients to be unaware of their options for end-of-life care. Providing
      educational materials and courses that have been developed from the ED
      perspective should be included in ongoing continuing medical education. Having a
      palliative care team that is responsive to the needs of the ED will further
      enhance collaboration with the ED. Future research should focus on understanding
      the range of benefits to having palliative care in the ED.

PMID- 22136263
TI  - The complexity of the etiology of autoimmune thyroid disease is gravely
      underestimated.

PMID- 22136264
TI  - E. Chester Ridgway delivers the first Lewis E. Braverman distinguished award
      lectureship at the American Thyroid Association's 2011 annual meeting.

PMID- 22136265
TI  - Papillary thyroid carcinoma patients assessed to be at low or intermediary risk
      after primary treatment are at greater risk of long term recurrence if they are
      thyroglobulin antibody positive or do not have distinctly low thyroglobulin at
      initial assessment.
AB  - BACKGROUND: In papillary thyroid carcinoma (PTC), recurrences during long-term
      follow-up (R-LTFU) occur even in those who appear to have an excellent prognosis
      after initial thyroid surgery and usually, radioactive iodine (i.e., "primary
      treatment"). Initial studies that predict R-LTFU are not well defined. Values for
      serum thyroglobulin (Tg) measurements when serum thyrotropin (TSH) is >30 MUU/mL,
      as a result of either recombinant TSH or L-thyroxine withdrawal, referred to here
      as stimulated Tg (STg), have been previously evaluated. The aim of the current
      study was to determine the parameters associated with R-LTFU in patients with PTC
      categorized as having low-risk disease 9 to 12 months after their primary
      treatment. METHODS: This was a retrospective study of 469 patients with PTC with
      a mean follow-up 5.8+/-3.9 years. Study patients had to have no uptake in the
      first postablative diagnostic (131)iodine whole body scan (WBS) performed 9-12
      months after primary treatment, a normal cervical ultrasonography (C-US), and STg
      of <2 ng/mL if their test for antithyroglobulin antibody (anti-Tg) was negative.
      The first two criteria were required for patients with a positive anti-Tg test,
      and their nominal serum Tg concentrations were not analyzed. RESULTS: Twelve
      patients developed recurrences (2.6%) in cervical region. Greater tumor size,
      higher STg, and positive anti-Tg tests at initial evaluation were associated with
      greater R-LTFU. The recurrence rates were 1.5% (7/450) and 26% (5/19),
      respectively, in patients with negative and positive anti-Tg tests at initial
      evaluation. Recurrence-free survival was lower in the patients with initial lymph
      node metastases, positive anti-Tg tests, and STg of >=0.3 ng/mL at the first
      postablative WBS (p=0.022, 0.001, 0.035, respectively, by log-rank test).
      Regression analysis in patients who were anti-Tg negative revealed that STg >=0.3
      ng/mL at this first WBS was the only parameter related to recurrence (p=0.031,
      odds ratio: 10.30, confidence interval: 1.23-83.3). CONCLUSION: Patients with PTC
      traditionally categorized as low risk during their first 9 to 12 months after
      primary treatment have a greater risk of R-LTFU if their postablative STg is
      >=0.3 ng/mL, or they have positive anti-Tg, even at this early stage. Periodic C
      US is important in these patients and should probably be more frequent in
      patients with PTC who have positive anti-Tg tests or STg >=0.3 ng/mL in the first
      year after diagnosis.

PMID- 22136266
TI  - Long-term outcome of comprehensive central compartment dissection in patients
      with recurrent/persistent papillary thyroid carcinoma.
AB  - BACKGROUND: Persistent or recurrent papillary thyroid carcinoma (PTC) occurs in
      some patients after initial thyroid surgery and often, radioactive iodine
      treatment. Here, we identify the efficacy, safety, and long-term outcome of our
      current surgical management paradigm for persistent/recurrent PTC in the central
      compartment in an interdisciplinary thyroid cancer clinical and research program
      at a tertiary thyroid cancer referral center. METHODS: We retrospectively
      analyzed our standardized approach of comprehensive bilateral level VI/VII lymph
      node dissection (SND [VI, VII]) for cytologically confirmed PTC in the central
      compartment. RESULTS: From 1994 to 2004, 210 patients, median age 42 (range 12
      82) underwent SND (VI, VII). Most patients (106, 51%) had already undergone >=2
      surgical procedures for persistent or recurrent disease, and 31 (15%) had distant
      metastases at presentation. Postoperatively, 104 (71%) of the 146 patients who
      were thyroglobulin (Tg) positive had no evidence of disease. Anti-Tg antibodies
      were present in 38 patients (18%), 17 of whom (53%) did not have anti-Tg
      antibodies postoperatively. Fourteen patients (7%) were hypoparathyroid at
      presentation, and 2 more (1%) became permanently hypoparathyroid after surgery.
      Four patients (2%) experienced recurrent laryngeal nerve paralysis (RLNP) of a
      previously functioning nerve. Unanticipated RLNP was observed in only one nerve
      at risk. External beam radiation was given to 33 patients (17%). An additional 17
      patients (8%) developed distant metastases during follow-up. At the last follow
      up, 130 (66%) of the 196 patients had no detectable Tg; of these, 99 (76%) had no
      further evidence of disease. A median of 7.25 years after surgery, 167 (90%) of
      the 185 patients were without evidence of central disease, and 18 (10%) had
      developed central compartment recurrences within a median interval of 24.3
      months. Of those with recurrence, 16 out of 18 patients (89%) underwent a
      subsequent surgical procedure, thus resulting in an overall 98% central
      compartment control rate. Kaplan-Meier disease-specific survival at 10 years was
      98.9% for patients <45 years old and 77.9% for those >=45 years old (log-rank
      p<0.00001). The only predictor of central compartment recurrence was malignancy
      in a thyroid remnant noted within the central compartment surgical specimen.
      CONCLUSIONS: Bilateral comprehensive level VI/VII dissections are safe and
      effective for long-term control of recurrent/persistent PTC in the central
      lymphatic compartment.

PMID- 22136267
TI  - In differentiated thyroid cancer, an incomplete structural response to therapy is
      associated with significantly worse clinical outcomes than only an incomplete
      thyroglobulin response.
AB  - BACKGROUND: We previously demonstrated the clinical utility of using response to
      therapy variables obtained during the first 2 years of follow-up to actively
      modify initial risk estimates which were obtained using standard clinic
      pathologic staging systems. While our proposed dynamic risk stratification system
      accurately reclassified patients who demonstrated an excellent response to
      therapy as low-risk patients, it grouped patients with either biochemical or
      structural evidence of disease into a single incomplete response to therapy
      cohort. This cohort included a wide variety of patients ranging from very minor
      thyroglobulin (Tg) elevations in the absence of structurally identifiable disease
      to widespread, progressive structural disease. Here we determined whether
      subdivision of the incomplete response to therapy category more precisely
      predicted clinical outcomes. We hypothesized that patients with an incomplete
      response to therapy based on persistently abnormal Tg values alone would have
      better clinical outcomes than patients having structurally identifiable disease.
      METHODS: Following total thyroidectomy and radioactive iodine (RAI) ablation, 192
      adult thyroid cancer patients were retrospectively identified as having either a
      biochemical incomplete response (abnormal Tg without structural evidence of
      disease) or structural incomplete response (structurally identifiable disease
      with or without abnormal Tg) as the best response to initial therapy within the
      first 24 months after RAI ablation. Clinical outcomes evaluated included
      structural disease progression, biochemical disease progression, and overall
      survival. RESULTS: Sixty-three patients (33%) had a biochemical incomplete
      response while 129 (67%) had a structural incomplete response. Eleven to 156
      months after evaluation of their responses (mean=70 months), patients with
      structural incomplete response were significantly more likely to have structural
      evidence of disease at final follow-up (37% vs. 17%, p=0.0004), structural
      progression (52% vs. 5%, p<0.001), biochemical progression (45% vs. 11%,
      p<0.001), and death from disease (38% vs. 0%, p<0.0001) than patients
      demonstrating a biochemical incomplete response. Overall survival was
      significantly better in patients with either a biochemical incomplete response or
      a loco-regional structural incomplete response than patients demonstrating a
      structural incomplete response with distant metastasis (Kaplan-Meier analysis,
      p<0.0001). CONCLUSIONS: A structural incomplete response to initial therapy is
      associated with significantly worse clinical outcome than a biochemical
      incomplete response to therapy.

PMID- 22136269
TI  - Intraoral removal of a thyroglossal duct cyst using a frenotomy incision.
AB  - BACKGROUND: Thyroglossal duct cyst (TGDC) is one of the most common causes of
      anterior neck swelling close to the midline. Surgical removal of a TGDC is
      usually accomplished through an external neck incision, including the removal of
      the middle part of hyoid bone and a block of tissues extending to the foramen
      cecum. However, this procedure inevitably results in a neck scar. METHODS: We
      report the case of a 20-year-old woman with TGDC. We implemented a modified
      approach to TGDC removal through a frenotomy incision of the mouth using an
      endoscope system. RESULTS: The patient received a modified approach to TGDC
      removal. The total operative time was 60 minutes. She remains free of disease 12
      months after her surgery. CONCLUSION: We describe, in a single patient, a
      procedure in detail for endoscope-assisted transoral TGDC excision using an
      intraoral frenotomy incision. The advantage of this approach is the avoidance of
      a neck scar. Our experience with this patient indicates that resection of a TGDC
      appears to be feasible through a transoral endoscope-assisted approach using a
      frenotomy incision in the mouth. Further experience with this procedure is
      required.

PMID- 22136268
TI  - Suitability of animal models for studying radiation-induced thyroid cancer in
      humans: evidence from nuclear architecture.
AB  - BACKGROUND: Rat and mouse have been widely used to estimate the radiation risk
      and tumorigenic effects of radiation with extrapolating the findings to humans.
      RET/PTC is a characteristic genetic alteration frequently found in radiation
      induced thyroid cancer in human populations. Recently, nuclear architecture and
      spatial proximity between recombinogenic genes have been implicated as important
      factors in the generation of RET/PTC and other chromosomal rearrangements in
      human cells. However, it is unknown whether the nuclear architecture in rodent
      thyroid cells is similar to that of human thyroid cells. The aim of this study
      was to test whether the proximity effects that are observed between loci involved
      in RET/PTC rearrangements in humans are conserved across different species.
      METHODS: Using 3D fixation, fluorescence in situ hybridization, and confocal
      microscopy, we compared the distance between genes involved in RET/PTC
      rearrangement in normal thyroid cells from humans, mice, and rats. RESULTS: While
      in humans, RET, NCOA4, and H4 are all located on the same chromosome (10q), in
      rodents these genes are located on separate chromosomes. In mouse, RET is located
      on chromosome 6F1, NCOA4 on 14B, and H4 on 10B5.3. In rat, RET is on chromosome
      4q42, NCOA4 on 16p16, and H4 (TST1) on 9q36. We further observed that in human
      thyroid cells, mean distance between genes involved in two most common types of
      RET/PTC, that is, RET and NCOA4 (partners of RET/PTC3) and RET and H4 (partners
      of RET/PTC1), was 1.08+/-0.04 and 1.24+/-0.05 MUm, respectively. In mouse thyroid
      cells, these distances were 3.21+/-0.1 and 3.43+/-0.1 MUm, and in rat cells the
      values were 3.37+/-0.1 and 3.87+/-0.1 MUm (p<0.001). Moreover, we found that in
      contrast to human thyroid cells, in rodent cells these genes were randomly
      positioned with respect to each other. CONCLUSIONS: The differences in nuclear
      architecture and spatial positioning of genes involved in RET/PTC rearrangements
      between human and rodent thyroid cells raise a concern about suitability of
      animal models for assessing RET/PTC-driven thyroid carcinogenesis in humans.

PMID- 22136270
TI  - BRAF(K601E) mutation in a patient with a follicular thyroid carcinoma.
AB  - BACKGROUND: BRAF mutations, the most common genetic alteration associated with
      papillary thyroid carcinoma (PTC), have never been associated with follicular
      thyroid carcinoma (FTC) except for one possible case, which, however, had some
      cellular features of the follicular variant of PTC. Here, we present a patient
      with a BRAF mutation within a FTC. SUMMARY: A 78-year-old man presented with a
      nodular lesion 8 cm in size in the right thyroid lobe, coexisting with a goiter.
      Fine-needle aspiration samples were obtained for cytology, immunocytology, and
      molecular analysis. Immunoblot analysis on thyroid tissues was performed to
      evaluate the most important tumor activating pathways. Cytology was consistent
      with "follicular neoplasia" (negative for galectin-3 immunostaining); molecular
      analysis on the cytology sample detected a K601E mutation in the exon 15 of the
      BRAF gene. After total thyroidectomy with lymph-node dissection, the diagnosis of
      FTC was established by histopathological examination. The BRAF(K601E) mutation
      was confirmed in DNA obtained from different areas of the FTC. In addition, an
      activating mutation (E545A) in the PKI3CA oncogene was found in the FTC. As
      expected, immunoblot analysis showed activation of the PI3K/Akt pathway.
      CONCLUSION: This article describes what may be the first case of a classical FTC
      carrying a BRAF mutation. Unlike the most common BRAF mutation seen in PTC
      carcinoma (BRAF(V600E)), this patient's mutation was a BRAF(K601E) mutation that
      previously has been associated with some cases of the follicular variant of PTC.
      The BRAF(K601E) mutation should be included in the spectrum of genetic
      alterations in FTC.

PMID- 22136274
TI  - Self-assembly of silver(I) and gold(I) N-heterocyclic carbene complexes in solid
      state, mesophase, and solution.
AB  - The assembly of silver(I) and gold(I) complexes of functionalized N-heterocyclic
      carbenes (NHCs) of the type [M(C(n),amide-imy)(2)][anion] were studied, in which
      C(n),amide-imy stands for an NHC of imidazol-2-ylidene having one N-alkyl
      substituent (C(n)H(2n+1)) and one N-acetamido substituent, while the anions are
      Br(-), NO(3)(-), BF(4)(-) or PF(6)(-). A single crystal X-ray diffraction study
      reveals that self-assembly of [Ag(C(10),amide-imy)(2)][PF(6)] through Coulombic,
      hydrogen bonding, and hydrophobic interactions gives a lamellar structure with
      tubular architecture around the metal ion head core. Self-assembly of these
      functionalized NHC complexes also leads to the formation of the first example of
      thermotropic liquid crystals of silver(I)-NHCs and gels of gold(I)-NHC. Results
      from an infrared spectroscopy study show that the degree of chain motion in the
      gel state is smaller than that in the mesophase, yet comparable to that in the
      solid state. In addition, the technique of nuclear magnetic resonance diffusion
      ordered spectroscopy was found for the first time to be a good tool to study the
      phase transition of gels. Xerogels of gold(I)-NHCs display fibers, oriental
      lantern-shaped bundles of belts and helical fibers when observed under scanning
      electron and transmission electron microscopes.

PMID- 22136271
TI  - Simultaneous occurrence of subacute thyroiditis and Graves' disease.
AB  - BACKGROUND: Rare cases of Graves' disease occurring years after subacute
      thyroiditis (SAT) have been reported. Here, we present the first known case of
      simultaneous occurrence of Graves' disease and SAT. PATIENT FINDINGS: A 41-year
      old woman presented with 10 days of neck pain, dysphagia, and hyperthyroid
      symptoms. Neck pain had initially started at the base of the right anterior neck
      and gradually spread to her upper chest, the left side of her neck, and bilateral
      ears. Physical examination revealed a heart rate of 110 beats/minute and a
      diffusely enlarged tender thyroid gland without evidence of orbitopathy. There
      was a resting tremor of the fingers and brisk deep tendon reflexes. Laboratory
      values: thyrotropin<0.01 mcIU/mL (nL 0.39-5.33), free thyroxine 2.0 ng/dL (nL
      0.59-1.60), free T3 6.6 pg/mL (nL 2.3-4.2), thyroglobulin 20.1 ng/mL (nL 2.0
      35.0), thyroglobulin antibody 843 IU/mL (nL 0-80), thyroperoxidase antibody 130
      IU/mL (nL 0-29), thyroid stimulating hormone receptor antibody 22.90 IU/L
      (nL<1.22), thyroid stimulating immunoglobulins 299 units (nL<140), erythrocyte
      sedimentation rate 120 mm/h (nL 0-20), and C-reactive protein 1.117 mg/dL (nL 0
      0.5). Human leukocyte antigen (HLA) typing revealed DRB1, DR8, B35, B39, DQB1,
      DQ4, and DQ5. A thyroid ultrasound showed an enlarged heterogeneous gland with
      mild hypervascularity. Fine-needle aspiration (FNA) biopsies of both thyroid
      lobes revealed granulomatous thyroiditis. The thyroid scan showed a diffusely
      enlarged gland and heterogeneous trapping. There was a focal area of relatively
      increased radiotracer accumulation in the right upper pole. The 5-hour uptake
      ((123)I) was 6.6% (nL 4-15). The patient was symptomatically treated. Over the
      next several weeks, she developed hypothyroidism requiring levothyroxine
      treatment. SUMMARY: This case illustrates a rare simultaneous occurrence of
      Graves' disease and SAT. Previous case studies have shown that Graves' disease
      may develop months to years after an episode of SAT. A strong family history of
      autoimmune thyroid disorders was noted in this patient. Genetic predilection was
      also shown by HLA typing. CONCLUSION: Although the occurrence of SAT with Graves'
      disease may be coincidental, SAT-induced autoimmune alteration may promote the
      development of Graves' disease in susceptible patients. Genetically mediated
      mechanisms, as seen in this patient by HLA typing and a strong family history,
      may also be involved.

PMID- 22136275
TI  - Identification and functional characterization of a primate-specific E2F1 binding
      motif regulating MCPH1 expression.
AB  - MCPH1 (also named BRIT1) is one of the known genes responsible for autosomal
      recessive primary microcephaly (small head syndrome), suggesting its important
      role in brain development. The interaction of MCPH1 with transcriptional factors
      like E2F1 is required for the activation of cell cycle checkpoint, DNA repair and
      apoptosis. However, the molecular mechanism of MCPH1 regulation is currently
      unclear. Here, we cloned the human MCPH1 promoter and we identified a novel E2F1
      binding motif located in the proximal promoter region of MCPH1. The experiments
      using electrophoretic mobility shift and promoter assays showed that E2F1 could
      stimulate MCPH1 transcription by direct binding to the E2F1 motif. Overexpression
      of E2F1 led to the upregulation of MCPH1 transcription, and knocking down the
      endogenous E2F1 resulted in the inhibition of the MCPH1 promoter activity.
      Surprisingly, sequence comparison of vertebrate species suggested that the
      identified E2F1 binding motif is primate specific, consistent with the previous
      observation of rapid evolution of MCPH1 protein sequence in primates. We propose
      that during primate evolution MCPH1 has acquired a novel E2F1 binding motif in
      its promoter which may act as a parallel mechanism, acting together with the
      rapid protein sequence changes in primates, and eventually contributed to brain
      enlargement during primate evolution and human origin. Database The MCPH1
      promoter region was sequenced in human, chimpanzee and rhesus macaque. Nucleotide
      sequence data are available in the GenBank database
      (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers JN573214, JN573215
      and JN573216.

PMID- 22136276
TI  - Everolimus: in patients with subependymal giant cell astrocytoma associated with
      tuberous sclerosis complex.
AB  - Everolimus is an orally administered inhibitor of the mammalian target of
      rapamycin (mTOR). Everolimus (starting dosage 3.0 mg/m(2)) was associated with a
      significant reduction in the volume of the largest subependymal giant cell
      astrocytoma (SEGA) in 28 patients aged >=3 years with tuberous sclerosis complex
      (TSC) in a phase II trial (C2485). At 6 months, 32% of patients treated with
      everolimus had a >=50% reduction in the volume of their largest SEGA lesion
      (assessed via an independent central radiology review); 75% had a >=30%
      reduction. No patients developed new lesions. During the extension phase of this
      trial (median duration 34 months), the reduction in SEGA volume was maintained,
      with no everolimus recipient requiring surgery or other therapy for SEGA or
      hydrocephalus. In a phase III trial (EXIST-1) in 117 patients with SEGA
      associated with TSC, 35% of everolimus recipients (starting dosage 4.5 mg/m(2))
      versus none of the placebo recipients (p < 0.0001) had an overall response (a
      reduction in the sum of all target SEGA volumes of >=50% relative to baseline,
      nonworsening of non-target SEGA lesions, no new SEGA lesions, and no
      new/worsening hydrocephalus). Everolimus was generally well tolerated in patients
      with SEGA associated with TSC; most drug-related adverse reactions were mild to
      moderate in severity.

PMID- 22136277
TI  - Correlation between serum calcium levels and dual-phase (99m)Tc-sestamibi
      parathyroid scintigraphy in primary hyperparathyroidism.
AB  - AIM: The goal of the study is to correlate serum calcium levels with the results
      of dual-phase (99m)Tc-sestamibi parathyroid scintigraphy to find the best cut-off
      level of the serum calcium that correlates with a positive presurgery. METHODS:
      In 111 patients, serum calcium and plasma parathormone (PTH) levels were compared
      with the results of the (99m)Tc-MIBI scintigraphy and with this data determined
      the level of calcium above which the (99m)Tc-MIBI scintigraphy was likely to be
      positive and below which the study was likely to be negative. RESULTS: In total,
      11 men (18%) and 50 women (82%) had a positive (99m)Tc-MIBI study. Overall 67% of
      those patients with a positive (99m)Tc-MIBI study had a PTH >200 ng l(-1)
      compared to only 9% of those with a negative (99m)Tc-MIBI scintigraphy; however,
      for those with a positive study on an early (99m)Tc-MIBI scintigraphy, this rose
      to 85%. Overall a serum calcium of >2.70 mmol l(-1) was found in 82% of patients
      with a positive (99m)Tc-MIBI study but only 14% of those with a negative (99m)Tc
      MIBI study, this is rose to 97% of patients with a parathyroid adenoma identified
      on early images. It is also shown that patients whose serum total calcium <2.51
      mmol l(-1) rarely have positive (99m)Tc-MIBI scintigraphy. CONCLUSION: (99m)Tc
      MIBI parathyroid scintigraphy is most likely to yield identification and
      localization of a parathyroid adenoma when both PTH and calcium are elevated;
      however, although there is no lower limit of PTH which can predict a negative
      study, we cannot recommend (99m)Tc-MIBI parathyroid scintigraphy if the serum
      calcium is <2.51 mmol l(-1).

PMID- 22136278
TI  - Leptin enhances maturation and development of calf oocytes in vitro.
AB  - We investigated the effects of leptin on the in vitro maturation (IVM) and
      development of calf oocytes. Cumulus-oocyte complexes were matured in IVM medium
      containing 0-100 ng/ml leptin. Experiment 1 showed that exposure of calf oocytes
      to IVM medium containing 1 or 10 ng/ml leptin significantly increased rates of
      development to the metaphase II stage compared with the control (81.7 +/- 3.0%
      and 83.3 +/- 2.1% for 1 and 10 ng/ml leptin, respectively, vs 64.1 +/- 5.1% for
      control; p < 0.05). Experiment 2 showed that 1 or 10 ng/ml leptin significantly
      improved cleavage rates after in vitro fertilization when compared to control
      (58.6 +/- 3.3% and 59.3 +/- 2.9% for 1 and 10 ng/ml leptin, respectively, vs 48.5
      +/- 2.6% for control; p < 0.05); in addition, when compared to control medium,
      the addition of 10 ng/ml leptin to the IVM medium resulted in more presumptive
      zygotes reaching the 4- to 8-cell stage after 48 h of in vitro culture (30.3 +/-
      2.3% vs 20.1 +/- 2.3%; p < 0.05) and developing into blastocysts after 8 days of
      culture (20.4 +/- 1.6% vs 11.7 +/- 1.7%; p < 0.05). Experiment 3 showed that the
      addition of 1 or 10 ng/ml leptin significantly increased the total number of
      blastocyst cells on day 8 of culture (114.6 +/- 7.8 and 117.4 +/- 5.9 for 1 and
      10 ng/ml leptin, respectively, vs 92.7 +/- 8.3 for control; p < 0.05) and
      trophectoderm (TE) cells (88.5 +/- 5.5 and 90.6 +/- 3.7 for 1 and 10 ng/ml
      leptin, respectively, vs 70.1 +/- 5.9 for control; p < 0.05). In summary, these
      results indicate that the addition of leptin to IVM medium enhances meiotic
      maturation and embryo development from calf oocytes and improves the quality of
      embryos derived from these oocytes.

PMID- 22136280
TI  - Water: a responsive small molecule.
AB  - Unique among small molecules, water forms a nearly tetrahedral yet flexible
      hydrogen-bond network. In addition to its flexibility, this network is dynamic:
      bonds are formed or broken on a picosecond time scale. These unique features make
      probing the local structure of water challenging. Despite the challenges, there
      is intense interest in developing a picture of the local water structure due to
      water's fundamental importance in many fields of chemistry.  Understanding
      changes in the local network structure of water near solutes likely holds the key
      to unlock problems from analyzing parameters that determine the three dimensional
      structure of proteins to modeling the fate of volatile materials released into
      the atmosphere. Pictures of the local structure of water are heavily influenced
      by what is known about the structure of ice. In hexagonal I(h) ice, the most
      stable form of solid water under ordinary conditions, water has an equal number
      of donor and acceptor bonds; a kind of symmetry. This symmetric tetrahedral
      coordination is only approximately preserved in the liquid. The most obvious
      manifestation of this altered tetrahedral bonding is the greater density in the
      liquid compared with the solid. Formation of an interface or addition of solutes
      further modifies the local bonding in water.  Because the O-H stretching
      frequency is sensitive to the environment, vibrational spectroscopy provides an
      excellent probe for the hydrogen-bond structure in water. In this Account, we
      examine both local interactions between water and small solutes and longer range
      interactions at the aqueous surface. Locally, the results suggest that water is
      not a symmetric donor or acceptor, but rather has a propensity to act as an
      acceptor. In interactions with hydrocarbons, action is centered at the water
      oxygen. For soluble inorganic salts, interaction is greater with the cation than
      the anion. The vibrational spectrum of the surface of salt solutions is altered
      compared with that of neat water. Studies of local salt-water interactions
      suggest that the picture of the local water structure and the ion distribution at
      the surface deduced from the surface vibrational spectrum should encompass both
      ions of the salt.

PMID- 22136279
TI  - Influence of the Chungkookjang on histamine-induced wheal and flare skin
      response: a randomized, double-blind, placebo controlled trial.
AB  - BACKGROUND: Allergic disease is a consequence of exposure to normally innocuous
      substances that elicit the activation of mast cells. Mast-cell-mediated allergic
      response is involved in many diseases such as anaphylaxis, urticaria, allergic
      rhinitis, asthma and allergic dermatitis. The development of food products for
      the prevention of allergic disease is an important subject in human health. The
      chungkookjang (CKJ) has been reported to exhibit antiallergic inflammatory
      activity. Therefore, the aim of the study is to examine the effects of the CKJ to
      reduce histamine-induced wheal and flare skin responses. METHODS/DESIGN: A
      randomized, double-blind, placebo-controlled study in 60 healthy subjects will be
      carried out. Sixty volunteers (aged 20-80) who gave a written consent before
      entering the study will be randomized in two groups of thirty subjects each. The
      skin prick test with histamine solution of 10 mg/ml will be performed on the
      ventral forearm, 10 cm from the elbow. The subjects will be instructed to take 35
      g per day of either the CKJ pills or a placebo pills for a period of 3 months.
      Diameters of wheal and flare will be assessing 15 minutes after performing the
      above-mentioned skin prick test. The primary outcome is change in wheal and flare
      responses. Secondary outcomes will be include change in serum histamine,
      immunoglobulin E, cytokines (interferon-gamma, interleukin-4, -10, and tumor
      necrosis factor-alpha), and eosinophil cationic protein. DISCUSSION: This study
      will show the potential anti-inflammatory properties of the CKJ in their skin
      activity when histamine is the challenging agent as occurs in the clinical
      situation. And the present protocol will confirm the efficacy and safety of the
      CKJ for allergy symptoms, suggesting more basic knowledge to conduct further
      randomized controlled trials (RCT). If this study will be successfully performed,
      the CKJ will be an alternative dietary supplemental remedy for allergy patients.
      TRIAL REGISTRATION: NCT01402141.

PMID- 22136281
TI  - Pioglitazone reduces peritoneal fibrosis via inhibition of TGF-beta, MMP-2, and
      MMP-9 in a model of encapsulating peritoneal sclerosis.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) and transforming growth factor beta
      (TGF-beta) were increased in peritoneal dialysis patients with encapsulating
      peritoneal sclerosis (EPS) and in chlorhexidine gluconate (CG)-induced peritoneal
      sclerosing animal models. Peroxisome proliferator-activated receptors (PPARs) are
      the major regulators of key metabolic pathways of various inflammatory responses
      in fibrosing processes in most tissues. The objective of this study was to
      investigate the effect of pioglitazone (Pio), a synthetic PPAR-gamma ligand, on
      the development of peritoneal fibrosis in CG-induced EPS rats. METHODS: Thirty
      two Wistar albino rats were intraperitoneally injected with saline (C group n =
      8) or with CG (1.5 mL/100 g; CG group, n = 8). Pio (30 mg/kg/day) was
      administered orally to another group of CG injected rats (the CG + Pio group, n =
      8) and to another control group (Pio group, n = 8) from initiation to the end of
      this study. After 14 days of Pio administration, the rats were killed and the
      parietal and visceral peritoneum were harvested. TGF-beta, MMP-2, MMP-9, tissue
      inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 activity assays and a
      morphological examination of the peritoneal tissues were performed. RESULTS: Pio
      significantly inhibited thickening of the submesothelial layer, fibrosis, and
      inflammation in the peritoneum. It also prevented increases in pro-MMP-2, pro-MMP
      9, TIMP-1, and TGF-beta activities. CONCLUSION: Pio, via MMP and TGF-beta
      inhibition, may lessen accumulation of peritoneal extracellular matrix and
      fibrosis to some extent in an EPS model and might be a new approach to the
      amelioration of EPS.

PMID- 22136282
TI  - Herbal remedies affecting coagulation: a review.
AB  - CONTEXT: Herbal remedies are used to treat a large variety of diseases, including
      blood-related disorders. However, a number of herbal preparations have been
      reported to cause variations in clotting time, this is mainly by disruption of
      the coagulation cascade. OBJECTIVE: The compiling of plants investigated for
      effects on the coagulation cascade. METHODS: Information was withdrawn from
      Google Scholar and the journal databases Scopus and PubMed. RESULTS: Sixty-five
      herbal remedies were identified with antiplatelet, anticoagulant, or coagulating
      ability. Bioactive compounds included polyphenols, taxanes, coumarins, saponins,
      fucoidans, and polysaccharides. CONCLUSION: Although research has been conducted
      on the effect of herbal remedies on coagulation, most information relies on in
      vitro assays. Contradictory evidence is present on bleeding risks with herbal
      uses, though herb-drug interactions pose a threat. As the safety of many herbals
      has not been proven, nor their effect on blood parameters determined, the use of
      herbal preparations before undergoing any surgical procedure should discontinued.

PMID- 22136283
TI  - Teamwork and team training in the ICU: where do the similarities with aviation
      end?
AB  - The aviation industry has made significant progress in identifying the skills and
      behaviors that result in effective teamwork. Its conceptualization of teamwork,
      development of training programs, and design of assessment tools are highly
      relevant to the intensive care unit (ICU). Team skills are important for
      maintaining safety in both domains, as multidisciplinary teams must work
      effectively under highly complex, stressful, and uncertain conditions. However,
      there are substantial differences in the nature of work and structure of teams in
      the ICU in comparison with those in aviation. While intensive care medicine may
      wish to use the advances made by the aviation industry for conceptualizing team
      skills and implementing team training programs, interventions must be tailored to
      the highly specific demands of the ICU.

PMID- 22136284
TI  - Deoxygenation of hydroquinones as a general route to norbornane-fused aromatic
      systems: an entry into substituted and functionalized dimethano- and
      methanoanthracenes.
AB  - A high-yielding route to substituted and functionalized dimethanoanthracenes by
      the Pd-catalyzed deoxyenation of the corresponding hydroquinone precursors is
      described. Attempts were made to deoxygenate the 9,10-dimesylate, ditosylate, and
      ditriflate derivatives of anti-dimethanoanthracene 1a, and it was found that
      under the studied conditions only the ditriflate 8a gave the corresponding
      deoxygenated aromatic scaffold. Optimization of the reaction conditions
      identified the Pd(OAc)(2)/dppf tandem as a suitable catalytic system for this
      transformation. The presented strategy was further extended to a novel and
      efficient synthetic route to methanoanthracenes employing a one-pot Pd-catalyzed
      deoxygenation/hydrogenation sequence.

PMID- 22136285
TI  - Aortic valve replacement for paraprosthetic leak after transcatheter
      implantation.
AB  - Conversion to surgical aortic valve replacement (AVR) has been described as a
      complication following transcatheter aortic valve implantation. This complication
      occurs in up to 8% of cases and, to the best of our knowledge, preoperative data
      and surgical outcomes of such patients have not been properly evaluated. Mild
      paraprosthetic regurgitation is commonly observed after transcatheter aortic
      valve implantation and usually leads to a benign clinical course. Unequal
      distribution of valve calcifications is described as a potential mechanism. We
      report a case of a perioperative paraprosthetic regurgitation that underwent
      successful urgent surgical AVR and review the incidence and results of
      paraprosthetic leaks following transcatheter implantation.

PMID- 22136286
TI  - Clinical features cannot distinguish allergic from non-allergic asthma in
      children.
AB  - OBJECTIVE: Environmental allergens are a major trigger of asthma, but not all
      asthmatics are allergic. This study was designed to review clinical
      characteristics in children with allergic and non-allergic asthma, based on
      responsiveness to allergy skin tests, in order to identify a combination of
      features that could distinguish allergic from non-allergic asthma in children.
      METHODS: Medical records of 321 children who had allergy skin testing were
      reviewed, and demographic and clinical data were compared between allergic and
      non-allergic patients. RESULTS: Approximately two-thirds of the asthmatic
      children had at least one positive skin test. These allergic patients were more
      likely to have a history of eczema or Medicaid insurance, but these findings had
      poor predictive value. There was no difference between allergic patients and non
      allergic patients in terms of family history of atopy or asthma, home tobacco
      smoke exposure, age of onset of asthma, gender, rate of obesity, or asthma
      severity. Among the allergic asthma patients, neither the number of positive skin
      tests nor specific individual allergic sensitivities correlated with age of onset
      of asthma or asthma severity. CONCLUSIONS: This study failed to identify any
      combination of features that could reliably distinguish allergic from non
      allergic asthma in children. Thus, all children with asthma should undergo
      allergy testing in order to identify potential allergic triggers in allergic
      patients and to avoid the institution of unnecessary environmental control
      measures in non-allergic patients.

PMID- 22136287
TI  - Optimization of preservation and storage time of sponge tissues to obtain quality
      mRNA for next-generation sequencing.
AB  - Transcriptome sequencing with next-generation sequencing technologies has the
      potential for addressing many long-standing questions about the biology of
      sponges. Transcriptome sequence quality depends on good cDNA libraries, which
      requires high-quality mRNA. Standard protocols for preserving and isolating mRNA
      often require optimization for unusual tissue types. Our aim was assessing the
      efficiency of two preservation modes, (i) flash freezing with liquid nitrogen
      (LN2) and (ii) immersion in RNAlater, for the recovery of high-quality mRNA from
      sponge tissues. We also tested whether the long-term storage of samples at -80 
      degrees C affects the quantity and quality of mRNA. We extracted mRNA from nine
      sponge species and analysed the quantity and quality (A260/230 and A260/280
      ratios) of mRNA according to preservation method, storage time, and taxonomy. The
      quantity and quality of mRNA depended significantly on the preservation method
      used (LN2) outperforming RNAlater), the sponge species, and the interaction
      between them. When the preservation was analysed in combination with either
      storage time or species, the quantity and A260/230 ratio were both significantly
      higher for LN2-preserved samples. Interestingly, individual comparisons for each
      preservation method over time indicated that both methods performed equally
      efficiently during the first month, but RNAlater lost efficiency in storage times
      longer than 2 months compared with flash-frozen samples. In summary, we find that
      for long-term preservation of samples, flash freezing is the preferred method. If
      LN2 is not available, RNAlater can be used, but mRNA extraction during the first
      month of storage is advised.

PMID- 22136288
TI  - Mutational complex genotype of the hepatitis B virus X /precore regions as a
      novel predictive marker for hepatocellular carcinoma.
AB  - This study explored the combined effect of number and pattern of mutations in the
      X/precore regions of the hepatitis B virus (HBV) genome, mutational complex
      genotype (MCG), on hepatocellular carcinoma (HCC) development. Sequence
      variations were determined by direct sequencing and multiplex restriction
      fragment mass polymorphism analysis in 150 age-, sex- and hepatitis B e antigen
      (HBeAg) status-matched patients with and without HCC. In addition, a longitudinal
      study and an external validation of MCG were conducted. All were HBV subgenotype
      C2. Eight high-frequency mutations (G1613A, C1653T, T1753V, A1762T, G1764A,
      A1846T, G1896A and G1899A) were significantly associated with HCC. Whereas
      C1653T, T1753V, G1764A and A1846T were independent mutational factors for HCC,
      the significance of these individual mutations was negligible when analyzed with
      all clinico-virological variables. The total number of mutations was the only
      independent viral factor for HCC, irrespective of HBeAg status. There was a
      significant dose-risk relationship between the number of mutations and HCC, in
      which high risks for HCC were associated with mutation numbers >= 6. Pattern
      analysis of the mutations revealed disparity in distribution among the top seven
      high-risk mutation combination patterns, which accounted for 40 and 2.7% of HCC
      and non-HCC cases, respectively. The predictive accuracy of the high-risk
      mutations for HCC was similar to that of alpha-fetoprotein. Longitudinal and
      external validation studies also supported the association of mutation number
      with HCC development. MCG in the HBV X/precore regions is a risk indicator for
      HCC, and might serve as a new guide to the HCC screening scheme for chronic HBV
      carriers.

PMID- 22136290
TI  - Computer-aided Medicine and Surgery.

PMID- 22136289
TI  - Insights into intermediate phases of human intestinal fluids visualized by atomic
      force microscopy and cryo-transmission electron microscopy ex vivo.
AB  - The current work aims to study at the ultrastructural level the morphological
      development of colloidal intermediate phases of human intestinal fluids (HIFs)
      produced during lipid digestion. HIFs were aspirated near the ligament of Treitz
      early (30 min), Aspirate(early), and 1 h, Aspirate(1h)(ave,comp), after the
      administration of a heterogeneous liquid meal into the antrum. The composition of
      the sample aspirated 1 h after meal administration was similar to the average
      lumenal composition 1 h after meal administration (Aspirate(1h)(ave,comp)). The
      colloidal structures of individual aspirates and supernatants of aspirates after
      ultracentrifugation (micellar phase) were characterized by means of atomic force
      microscopy (AFM) and cryogenic transmission electron microscopy (Cryo-TEM). AFM
      revealed domain-like structures in Aspirate(early) and both vesicles and large
      aggregates Aspirate(1h)(ave,comp). Rough surfaces and domains varying in size
      were frequently present in the micellar phase of both Aspirate(early) and
      Aspirate(1h)(ave,comp). Cryo-TEM revealed an abundance of spherical micelles and
      occasionally presented worm-like micelles coexisting with faceted and less
      defined vesicles in Aspirate(early) and Aspirate(1h)(ave,comp). In
      Aspirate(1h)(ave,comp) oil droplets were visualized with bilayers closely located
      to their surface suggesting lipolytic product phases accumulated on the surface
      of the oil droplet. In the micellar phase of Aspirate(early), Cryo-TEM revealed
      the presence of spherical micelles, small vesicles, membrane fragments, oil
      droplets and plate-like structures. In the micellar phase of
      Aspirate(1h)(ave,comp) the only difference was the absence of oil droplets.
      Visualization studies previously performed with biorelevant media revealed
      structural features with many similarities as presented in the current
      investigation. The impression of the complexity and diversion of these phases has
      been reinforced with the excessive variation of structural features visualized ex
      vivo in the current study offering insights at the ultrastuctural level of
      intermediate phases which impact drug solubilization.

PMID- 22136291
TI  - Structural frustration and occupational disorder: the rare earth metal
      polysulfides Tb8S(14.8), Dy8S(14.9), Ho8S(14.9), and Y8S(14.8).
AB  - Dark red crystals of Y8S(14.8), Tb8S(14.8), Dy8S(14.9), and Ho8S(14.9) have been
      obtained following different reaction routes. The isostructural title compounds
      adopt the Gd8Se15 type, a 24-fold superstructure of the ZrSSi-type and can be
      described in space group A112 (non standard setting of C121, no. 5) with lattice
      parameter of a = 11.505(1) A, b = 15.385(1) A, c = 15.726(1) A, and gamma =
      90.21(2) degrees  for Y8S(15-x); a = 11.660(1) A, b = 15.468(2) A, c = 15.844(2)
      A, and gamma = 90.19(2) degrees  for Tb8S(15-x); a = 11.584(1) A, b = 15.340(2)
      A, c = 15.789(2) A, and gamma = 90.34(2) degrees  for Dy8S(15-x); and a =
      11.538(1) A, b = 15.288(2) A, c = 15.740(2) A, and gamma = 90.23(1) degrees  for
      Ho8S(15-x), respectively. The structure consists of an alternating stacking of
      puckered [RES] (RE, rare-earth metals) double slabs and planar sulfur layers
      along [001]. The planar sulfur layers have a complex arrangement of S22-
      dinuclear dianions, isolated S2- ions, and vacancies. All compounds contain
      trivalent rare-earth metal ions, for Tb8S(15-x) and Dy8S(15-x) antiferromagnetic
      order was found at T(N) = 5.4(2) K and 3.8(1) K, respectively. Short wavelength
      cutoff optical band gaps of 1.6 to 1.7 eV were determined.

PMID- 22136292
TI  - The higher exercise intensity and the presence of allele I of ACE gene elicit a
      higher post-exercise blood pressure reduction and nitric oxide release in elderly
      women: an experimental study.
AB  - BACKGROUND: The absence of the I allele of the angiotensin converting enzyme
      (ACE) gene has been associated with higher levels of circulating ACE, lower
      nitric oxide (NO) release and hypertension. The purposes of this study were to
      analyze the post-exercise salivary nitrite (NO2-) and blood pressure (BP)
      responses to different exercise intensities in elderly women divided according to
      their ACE genotype. METHODS: Participants (n = 30; II/ID = 20 and DD = 10)
      underwent three experimental sessions: incremental test - IT (15 watts workload
      increase/3 min) until exhaustion; 20 min exercise 90% anaerobic threshold (90%
      AT); and 20 min control session without exercise. Volunteers had their BP and NO2
      measured before and after experimental sessions. RESULTS: Despite both
      intensities showed protective effect on preventing the increase of BP during post
      exercise recovery compared to control, post-exercise hypotension and increased
      NO2- release was observed only for carriers of the I allele (p < 0.05).
      CONCLUSION: Genotypes of the ACE gene may exert a role in post-exercise NO
      release and BP response.

PMID- 22136293
TI  - Protocol: high throughput silica-based purification of RNA from Arabidopsis
      seedlings in a 96-well format.
AB  - The increasing popularity of systems-based approaches to plant research has
      resulted in a demand for high throughput (HTP) methods to be developed. RNA
      extraction from multiple samples in an experiment is a significant bottleneck in
      performing systems-level genomic studies. Therefore we have established a high
      throughput method of RNA extraction from Arabidopsis thaliana to facilitate gene
      expression studies in this widely used plant model. We present optimised manual
      and automated protocols for the extraction of total RNA from 9-day-old
      Arabidopsis seedlings in a 96 well plate format using silica membrane-based
      methodology. Consistent and reproducible yields of high quality RNA are isolated
      averaging 8.9 MUg total RNA per sample (~20 mg plant tissue). The purified RNA is
      suitable for subsequent qPCR analysis of the expression of over 500 genes in
      triplicate from each sample. Using the automated procedure, 192 samples (2 * 96
      well plates) can easily be fully processed (samples homogenised, RNA purified and
      quantified) in less than half a day. Additionally we demonstrate that plant
      samples can be stored in RNAlater at -20 degrees C (but not 4 degrees C) for 10
      months prior to extraction with no significant effect on RNA yield or quality.
      Additionally, disrupted samples can be stored in the lysis buffer at -20 degrees
      C for at least 6 months prior to completion of the extraction procedure providing
      a flexible sampling and storage scheme to facilitate complex time series
      experiments.

PMID- 22136294
TI  - Assessing the contribution of prescribing in primary care by nurses and
      professionals allied to medicine: a systematic review of literature.
AB  - BACKGROUND: Safe and timely access to effective and appropriate medication
      through primary care settings is a major concern for all countries addressing
      both acute and chronic disease burdens. Legislation for nurses and other
      professionals allied to medicine to prescribe exists in a minority of countries,
      with more considering introducing legislation. Although there is variation in the
      range of medicines permitted to be prescribed, questions remain as to the
      contribution prescribing by nurses and professionals allied to medicine makes to
      the care of patients in primary care and what is the evidence on which
      clinicians, commissioners of services and policy makers can consider this
      innovation. METHODS: A integrative review of literature on non-medical
      prescribing in primary care was undertaken guided by dimensions of health care
      quality: effectiveness, acceptability, efficiency and access. RESULTS: 19 papers
      of 17 empirical studies were identified which provided evidence of patient
      outcome of non medical prescribing in primary care settings. The majority were
      undertaken in the UK with only one each from the USA, Canada, Botswana and
      Zimbabwe. Only two studies investigated clinical outcomes of non-medical
      prescribing. Seven papers reported on qualitative designs and four of these had
      fewer than ten participants. Most studies reported that non medical prescribing
      was widely accepted and viewed positively by patients and professionals.
      CONCLUSIONS: Primary health care is the setting where timely access to safe and
      appropriate medicines is most critical for the well-being of any population. The
      gradual growth over time of legislative authority and in the numbers of non
      medical prescribers, particularly nurses, in some countries suggests that the
      acceptability of non-medical prescribing is based on the perceived value to the
      health care system as a whole. Our review suggests that there are substantial
      gaps in the knowledge base to help evidence based policy making in this arena. We
      suggest that future studies of non-medical prescribing in primary care focus on
      the broad range of patient and health service outcomes and include economic
      dimensions.

PMID- 22136296
TI  - Initial cord blood unit volume affects mononuclear cell and CD34+ cell-processing
      efficiency in a non-linear fashion.
AB  - BACKGROUND AIMS: Umbilical cord blood (UCB) is a source of hematopoietic stem
      cells that initially was used exclusively for the hematopoietic reconstitution of
      pediatric patients. It is now suggested for use for adults as well, a fact that
      increases the pressure to obtain units with high cellularity. Therefore, the
      optimization of UCB processing is a priority. METHODS: The present study focused
      on parameters influencing total nucleated cell (TNC), mononucleated cell (MNC)
      and CD34+ cell (CD34C) recovery after routine volume reduction of 1553 UCB units
      using hydroxyethyl starch-induced sedimentation with an automated device, under
      routine laboratory conditions. RESULTS: We show that the unit volume rather than
      the TNC count significantly affects TNC, MNC and CD34C processing efficiency
      (PEf), and this in a non-linear fashion: when units were sampled according to the
      collection volume, including pre-loaded anticoagulant (gross volume), PEf
      increased up to a unit volume of 110-150 mL and decreased thereafter. Thus units
      with initial gross volumes < 90 mL and > 170 mL similarly exhibited a poor PEf.
      CONCLUSIONS: These data identify unit gross volume as a major parameter
      influencing PEf and suggest that fractionation of large units should be
      contemplated only when the resulting volume of split units is > 90 mL.

PMID- 22136295
TI  - Activated T cells modulate immunosuppression by embryonic-and bone marrow-derived
      mesenchymal stromal cells through a feedback mechanism.
AB  - BACKGROUND AIMS: Human embryonic stem cell (hESC)-derived mesenchymal stromal
      cells (MSC) (hESC-MSC) are an alternative source of MSC to bone marrow (BM)
      derived MSC (BM-MSC), which are being investigated in clinical trials for their
      immunomodulatory potential. hESC-MSC have the advantage of being consistent
      because each batch can be generated from hESC under defined conditions. In
      contrast, BM-MSC have a limited proliferative capacity. METHODS: The ability to
      suppress the proliferation of anti-CD3/CD28-stimulated CD4 (+) T cells by hESC
      MSC was compared with adult BM-MSC and neonatal foreskin fibroblast (Fb).
      RESULTS: hESC-MSC suppress the proliferation of CD4 (+) T cells in both contact
      and transwell systems, although inhibition is less in the transwell system. hESC
      MSC are approximately 2-fold less potent (67 cells/100 T cells) than BM-MSC and
      Fb (37 and 34 cells/100 T cells, respectively) at suppressing T-cell
      proliferation by 50% in a transwell [inhibitory concentration(IC)(50)]. The anti
      proliferative effect is not contact-dependent but requires the presence of
      factors such as interferon (IFN)-gamma produced by activated T cells. IFN-gamma
      induces the expression of indoleamine-2,3-dioxygenase (IDO) in hESC-MSC, BM-MSC
      and Fb, contributing to their immunosuppressive property. CONCLUSIONS: The
      feedback loop between MSC or Fb and activated T cells may limit the
      immunosuppressive effects of MSC and Fb to sites containing ongoing immunologic
      or inflammatory responses where activated T cells induce the up-regulation of IDO
      and immunomodulatory properties of MSC and Fb. These data demonstrate that hESC
      MSC may be evaluated further as an allogeneic cell source for therapeutic
      applications requiring immunosuppression.

PMID- 22136297
TI  - Self-perception of weight gain among multiethnic reproductive-age women.
AB  - OBJECTIVE: To examine the accuracy of self-perception of weight gain and its
      correlates in a multiethnic reproductive-age population of women. METHODS: A
      total of 608 women (balanced by contraceptive methods and race/ethnicity) self
      reported their perceptions of weight gain at baseline and every 6 months
      thereafter for 36 months. Data regarding body weight, height, and other
      covariates were also obtained. Women with at least two follow-up visits were
      included in the final analysis. Generalized estimating equations (GEE) models
      were used to examine correlates of the accuracy of self-perception of weight gain
      over time. RESULTS: Overall, 466 women had at least two follow-up visits with
      1744 total observations over 36 months. In total, 44%, 30%, 19%, 12%, and 8%
      observations had at least 1, 2, 3, 4, and 5 kg weight gain in 6 months while 59%,
      67%, 73%, 78%, and 85% of women accurately recognized it, respectively. Depot
      medroxyprogesterone (DMPA) users were more likely than nonhormonal method users
      (69%/51%, 76%/59%, 81%/63%, 85%/59%, and 93%/71%), and blacks more likely than
      whites (70%/51%, 76%/59%, 83%/65%, 90%/68%, and 95%/78%) (p<0.05 for all) to
      recognize weight gains of 1, 2, 3, 4, and 5 kg. The differences remained
      significant after adjusting for covariates using GEE. A significant difference
      was also observed between DMPA and oral contraceptive users. CONCLUSIONS:
      Inability to recognize weight gain is common among young women. Both
      race/ethnicity and contraceptive methods influence the accurate perception of
      weight gain. Clinicians should provide patient-specific counseling to address the
      frequent inaccuracies to recognize weight gain.

PMID- 22136298
TI  - Lifestyle intervention and cardiovascular risk reduction in the Illinois
      WISEWOMAN Program.
AB  - BACKGROUND: The Illinois WISEWOMAN Program (IWP) was designed to address the
      disproportionate risk of cardiovascular disease (CVD) among disadvantaged, low
      income women. In total, 1021 women aged 40 to 64 years were recruited from the
      Illinois Breast and Cervical Cancer Program. The women were randomized to either
      a minimum intervention (MI) or an enhanced intervention (EI) group. Both groups
      received CVD risk factor screening and educational materials, and the EI group
      received a 12-week lifestyle change intervention. METHODS: Demographic and
      clinical data were collected in addition to data on CVD risk, which was measured
      in terms of nutritional and physical activity behavior, using culturally adapted
      versions of three valid and reliable questionnaires. IWP data were analyzed for
      demographic characteristics and clinical and behavioral outcomes at baseline,
      post-intervention, and follow-up at 1 and 2 years from baseline. This article
      reports the change in these outcomes up to the 1-year follow-up. RESULTS:
      Participants in the EI group showed significant improvement on some of the
      dietary and physical activity outcomes both at post-intervention and 1-year
      follow-up. Compared with the MI group, the EI group showed more improvement in
      dietary fat- and fiber-related behaviors and increased physical activity levels.
      There were improvements in all of the cardiovascular outcomes at post
      intervention in both the EI and MI groups; however, these changes were not
      statistically significant. CONCLUSION: As an integrated physical activity and
      nutrition intervention, the IWP has shown its strength in addressing some of the
      lifestyle behaviors for CVD prevention in this at-risk target population.

PMID- 22136299
TI  - A survey of congenital reproductive abnormalities in rams in abattoirs in South
      west England.
AB  - Congenital abnormalities of the reproductive tract of male sheep were surveyed at
      three abattoirs in the south west of England during the period June 2000-January
      2004. A total of 7307 rams were examined [6521 lambs (prepubescent) and hoggets
      (aged from their first autumn after birth until first shorn) and 786 adult rams
      mature rams that had been exposed to ewes]. A total of 156 congenital lesions
      were detected, 87 of which occurred in lambs. Testicular hypoplasia was the most
      common lesion occurring in 69 lambs as well as eight hoggets ('microtestes' were
      recognized in nine other animals in which the testis was disproportionately
      smaller than the epididymis). The second most common lesion found was notched
      scrotum occurring in 34 animals (27 young rams and seven adults). Some cases of
      notched scrotum were accompanied by hypospadias which was seen in a total of
      seven lambs and eight hoggets. Other lesions, detected in five or less animals
      (less than approximately 0.05% of the animals examined), included cryptorchidism
      and various abnormalities of the epididymis (segmental aplasia of the epididymis,
      blind efferent ducts and epididymal cyst) and congenital scrotal hernia. The
      overall prevalence of congenital lesions of 2.21% emphasizes the importance of
      undertaking breeding soundness examinations of young rams before they are put
      with the flock.

PMID- 22136300
TI  - Kinetic analysis of 3'-5' nucleotide addition catalyzed by eukaryotic tRNA(His)
      guanylyltransferase.
AB  - The tRNA(His) guanylyltransferase (Thg1) catalyzes the incorporation of a single
      guanosine residue at the -1 position (G(-1)) of tRNA(His), using an unusual 3'-5'
      nucleotidyl transfer reaction. Thg1 and Thg1 orthologs known as Thg1-like
      proteins (TLPs), which catalyze tRNA repair and editing, are the only known
      enzymes that add nucleotides in the 3'-5' direction. Thg1 enzymes share no
      identifiable sequence similarity with any other known enzyme family that could be
      used to suggest the mechanism for catalysis of the unusual 3'-5' addition
      reaction. The high-resolution crystal structure of human Thg1 revealed remarkable
      structural similarity between canonical DNA/RNA polymerases and eukaryotic Thg1;
      nevertheless, questions regarding the molecular mechanism of 3'-5' nucleotide
      addition remain. Here, we use transient kinetics to measure the pseudo-first
      order forward rate constants for the three steps of the G(-1) addition reaction
      catalyzed by yeast Thg1: adenylylation of the 5' end of the tRNA (k(aden)),
      nucleotidyl transfer (k(ntrans)), and removal of pyrophosphate from the G(-1)
      containing tRNA (k(ppase)). This kinetic framework, in conjunction with the
      crystal structure of nucleotide-bound Thg1, suggests a likely role for two-metal
      ion chemistry in all three chemical steps of the G(-1) addition reaction.
      Furthermore, we have identified additional residues (K44 and N161) involved in
      adenylylation and three positively charged residues (R27, K96, and R133) that
      participate primarily in the nucleotidyl transfer step of the reaction. These
      data provide a foundation for understanding the mechanism of 3'-5' nucleotide
      addition in tRNA(His) maturation.

PMID- 22136302
TI  - Australian newspaper coverage of human papillomavirus vaccination, October 2006
      December 2009.
AB  - Vaccination against human papillomavirus (HPV) is now routine practice for
      adolescent females in Australia. Media information about HPV vaccination is
      likely to affect girls' and parents' decisions about vaccination. This article
      reports a content analysis of 131 Australian print media news stories published
      between October 2006 and December 2009. Each story was coded for main themes of
      the article; completeness and accuracy of information presented; potential issues
      and concerns related to HPV vaccination; phrasing, emphasis, and language used;
      and representation of experts. Resulting themes were as follows: Australian pride
      in vaccine development; details and progress of the National Vaccination Program;
      vaccine safety; HPV vaccination's future; whether or not males could and/or
      should get the vaccine; issues related to sexual activity and the vaccine; and
      issues about decision making for acceptance of HPV vaccine. To fill gaps that are
      created by media representations of HPV vaccination, educational interventions
      should include information about HPV transmission and male vaccination and should
      promote adolescent involvement in decision making.

PMID- 22136301
TI  - Apoptotic activity of the marine diatom Cocconeis scutellum and eicosapentaenoic
      acid in BT20 cells.
AB  - CONTEXT: The marine diatoms Cocconeis scutellum Ehrenberg (Bacillariophyceae) are
      known to trigger apoptosis in the androgenic gland of the Mediterranean
      crustacean Hippolyte inermis Leach (Decapoda), affecting the shrimp's sex
      reversal. OBJECTIVE: The aim of this study was to evaluate a possible apoptotic
      effect of extracts and fractions from these microalgae also on human tissues.
      MATERIALS AND METHODS: The chemical profile of C. scutellum was determined by gas
      chromatography-mass spectrometry (GC-MS) and, afterwards, organic extracts and
      fractions from the diatoms were used to treat to breast cancer BT20 cells. Double
      labeling with annexin V-FITC and isotonic propidium iodide (PI) along with flow
      cytometry analysis enabled the evaluate of cell apoptosis and viability, whereas
      hypotonic PI staining was used to analyze the cell cycle in BT20 lines. The
      involvement of specific caspases was studied by Western blotting. RESULTS:
      Results demonstrated that the diethyl ether extract and, in particular, fraction
      3, the richest fraction in eicosapentaenoic acid (EPA) from the diethyl ether
      extract, selectively induced apoptosis (up to 89.2% at 1 MUg/well of fraction 3)
      and decreased viability in BT20 cells. The apoptotic effect was displayed in a
      concentration and time-dependent manner, by activating caspases-8 and 3, and
      arresting the progression of the cell cycle from S to G2-M phase. EPA alone
      showed similar apoptotic effects in BT20 cells. DISCUSSION AND CONCLUSION: The
      study demonstrates the apoptotic activity of C. scutellum diatoms on breast
      cancer cells and suggests their potential use as a source of apoptotic compounds.

PMID- 22136303
TI  - Dronedarone for the treatment of atrial fibrillation: a NICE single technology
      appraisal.
AB  - The National Institute for Health and Clinical Excellence (NICE) invited the
      manufacturer of dronedarone (Multaq(r), Sanofi-Aventis Limited, UK) to submit
      evidence on the clinical and cost effectiveness of the anti-arrhythmic drug (AAD)
      for the treatment of atrial fibrillation (AF) and atrial flutter, as part of the
      Institute's single technology appraisal (STA) process. The Centre for Reviews and
      Dissemination and the Centre for Health Economics, both at the University of
      York, were commissioned to act as the independent Evidence Review Group (ERG).
      This article provides a description of the company submission, the ERG review and
      NICE's subsequent decisions regarding the use of dronedarone within the UK NHS.
      The ERG review comprised a critique of the submitted evidence on the clinical
      effectiveness and cost effectiveness of dronedarone. The ERG examined the search
      strategy used to obtain relevant evidence, the selection of studies included in
      the assessment, outcome measures chosen and statistical methods employed. The ERG
      also validated the manufacturer's decision analytic model and used it to explore
      the robustness of the cost-effectiveness results to key assumptions. The main
      clinical effectiveness evidence supporting the use of dronedarone as a treatment
      for AF came from four randomized controlled trials. These trials were compared
      with a broader set of trials examining the effectiveness of other AADs for AF:
      amiodarone, sotalol and class 1c agents (flecainide and propafenone). The
      evidence suggested that all AADs decreased the recurrence of AF but dronedarone
      had the smallest effect. A mixed treatment comparison analysis of the trials
      showed that dronedarone was associated with a lower risk of all-cause mortality
      than other AADs, but this was highly uncertain. There was limited evidence to
      assess the effect of dronedarone on stroke, and no statistically significant
      differences between dronedarone and other AADs were found for treatment
      discontinuation. From the evidence presented by the manufacturer, dronedarone
      appeared highly cost effective in each of the population groups examined compared
      with using standard baseline therapy alone as first-line treatment, or compared
      with sotalol or amiodarone as first-line AAD, with incremental cost-effectiveness
      ratios (ICERs) well below L20,000 per QALY gained. The ICER for dronedarone
      relative to class 1c agents was around L19,000 per QALY. Although the evidence
      presented by the manufacturer indicated that dronedarone was cost effective, the
      estimates of treatment effect relative to other AADs and safety in the longer
      term were highly uncertain. The NICE Appraisal Committee in its preliminary
      guidance did not recommend the use of dronedarone for AF. However, following the
      response from a large number of consultees and commentators, NICE revised its
      preliminary guidance to allow the use of the drug in a specific subgroup of AF
      patients with additional cardiovascular risk factors.

PMID- 22136304
TI  - Direct arylation of arene and N-heteroarenes with diaryliodonium salts without
      the use of transition metal catalyst.
AB  - A novel and simple transition metal-free direct arylation of arene and N
      heteroarenes with diaryliodonium salts has been developed. This cross-coupling
      reaction is promoted only by base and gives the desired products in moderate to
      good yields.

PMID- 22136305
TI  - Clinical review: Optimizing enteral nutrition for critically ill patients--a
      simple data-driven formula.
AB  - In modern critical care, the paradigm of 'therapeutic nutrition' is replacing
      traditional 'supportive nutrition'. Standard enteral formulas meet basic macro-
      and micronutrient needs; therapeutic enteral formulas meet these basic needs and
      also contain specific pharmaconutrients that may attenuate hyperinflammatory
      responses, enhance the immune responses to infection, or improve gastrointestinal
      tolerance. Choosing the right enteral feeding formula may positively affect a
      patient's outcome; targeted use of therapeutic formulas can reduce the incidence
      of infectious complications, shorten lengths of stay in the ICU and in the
      hospital, and lower risk for mortality. In this paper, we review principles of
      how to feed (enteral, parenteral, or both) and when to feed (early versus delayed
      start) patients who are critically ill. We discuss what to feed these patients in
      the context of specific pharmaconutrients in specialized feeding formulations,
      that is, arginine, glutamine, antioxidants, certain omega-3 and omega-6 fatty
      acids, hydrolyzed proteins, and medium-chain triglycerides. We summarize current
      expert guidelines for nutrition in patients with critical illness, and we present
      specific clinical evidence on the use of enteral formulas supplemented with anti
      inflammatory or immune-modulating nutrients, and gastrointestinal tolerance
      promoting nutritional formulas. Finally, we introduce an algorithm to help
      bedside clinicians make data-driven feeding decisions for patients with critical
      illness.

PMID- 22136306
TI  - Single-particle studies of band alignment effects on electron transfer dynamics
      from semiconductor hetero-nanostructures to single-walled carbon nanotubes.
AB  - We utilize single-molecule spectroscopy combined with time-correlated single
      photon counting to probe the electron transfer (ET) rates from various types of
      semiconductor hetero-nanocrystals, having either type-I or type-II band
      alignment, to single-walled carbon nanotubes. A significantly larger ET rate was
      observed for type-II ZnSe/CdS dot-in-rod nanostructures as compared to type-I
      spherical CdSe/ZnS core/shell quantum dots and to CdSe/CdS dot-in-rod structures.
      Furthermore, such rapid ET dynamics can compete with both Auger and radiative
      recombination processes, with significance for effective photovoltaic operation.

PMID- 22136308
TI  - Late migration of percutaneous bio-absorbable devices--a word of caution.
AB  - BACKGROUND: Closures of atrial septal defects or a patent foramen ovale (PFO) are
      increasingly performed percutaneously. The experience of late migration of a new
      bio-absorbable device is presented here, followed by conceptual discussion.
      METHODS: Six months post PFO closure with a BioSTAR(r) device a patient presented
      with chest pain. Echocardiography showed a hyperechogenic structure perforating
      the aortic wall. RESULTS: Surgical exploration showed a perforation of the
      ascending aorta by one metallic, non absorbable arm. This is the second case of
      late (>6 months) dislocation of the residual framework of the occluder.
      CONCLUSIONS: The overall incidence of perforation of cardiac structures due to
      secondary dislocation is low. However this complication exists and should kept in
      mind in symptomatic patients with new onset of chest pain, after percutaneous
      procedures. The concept of biodegradation, with residual, non absorbable metal
      braiding, should be reviewed, analyzing in particular long term results and
      incidence of secondary dislocation.

PMID- 22136309
TI  - Dysregulation of melanocyte function by Th17-related cytokines: significance of
      Th17 cell infiltration in autoimmune vitiligo vulgaris.
AB  - The aim of this study was to determine whether CD4(+) IL-17A(+) Th17 cells
      infiltrate vitiligo skin and to investigate whether the proinflammatory cytokines
      related to Th17 cell influence melanocyte enzymatic activity and cell fate. An
      immunohistochemical analysis showed Th17 cell infiltration in 21 of 23 vitiligo
      skin samples in addition to CD8(+)  cells on the reticular dermis. An in vitro
      analysis showed that the expression of MITF and downstream genes was
      downregulated in melanocytes by treatment with interleukin (IL)-17A, IL-1beta, IL
      6, and tumor necrosis factor (TNF)-alpha. Treatment with these cytokines also
      induced morphological shrinking in melanocytes, resulting in decreased melanin
      production. In terms of local cytokine network in the skin, IL-17A dramatically
      induced IL-1beta, IL-6, and TNF-alpha production in skin-resident cells such as
      keratinocytes and fibroblasts. Our results provide evidence of the influence of a
      complex Th17 cell-related cytokine environment in local depigmentation in
      addition to CD8(+)  cell-mediated melanocyte destruction in autoimmune vitiligo.

PMID- 22136310
TI  - Optimizing biochemical markers as endpoints for clinical trials in primary
      biliary cirrhosis.
AB  - BACKGROUND: Biochemical tests have been recommended as endpoints for clinical
      trials in primary biliary cirrhosis (PBC) because the use of liver
      transplantation and death as endpoints in ursodeoxycholic acid (UDCA) therapeutic
      trials is unfeasible. The best inclusion criteria cut-off values and cut-off for
      demonstrating treatment success have not been defined. AIM: Our aim was to
      determine the optimal biochemical values for patient inclusion and to define
      values for treatment success in therapeutic trials. METHODS: We performed a
      retrospective review of 73 patients with PBC treated with UDCA followed over 36
      months. Following one year of UDCA therapy, the likelihood of developing clinical
      endpoints of varices, ascites, encephalopathy, death or transplantation over the
      ensuing two years, based on degrees of elevation of biochemical markers, was
      analyzed using chi-square or Fisher's exact test. RESULTS: Patients with ALP>=2 X
      upper limit of normal (ULN) had a 2-fold greater likelihood of developing
      endpoints compared to patients with lower values (23% versus 11%), (p < 0.05).
      Patients with bilirubin > 1 mg/dL were 4 times more likely to develop endpoints
      compared to those with lower values (33% versus 8%), (p = 0.02). These values
      help identify the patient population for adjunctive therapy trials. Patients with
      ALP <=1.67 X ULN and bilirubin <=1mg/dL demonstrated the least likelihood of
      reaching adverse clinical endpoints and can be used to define treatment success.
      CONCLUSION: Optimal ALP and Bilirubin levels can be used as appropriate
      biochemical criteria for patient selection and defining treatment success in
      future clinical trials in patients with PBC.

PMID- 22136311
TI  - The degree of erythema in melasma lesion is associated with the severity of
      disease and the response to the low-fluence Q-switched 1064-nm Nd:YAG laser
      treatment.

PMID- 22136313
TI  - Evolution of drug resistance in cancer: the emergence of unique mechanisms and
      novel techniques.

PMID- 22136314
TI  - Preface: A physical sciences perspective of the evolution of drug resistance in
      cancer.

PMID- 22136312
TI  - Synthesis and evaluation of 1,5-disubstituted tetrazoles as rigid analogues of
      combretastatin A-4 with potent antiproliferative and antitumor activity.
AB  - Tubulin, the major structural component of microtubules, is a target for the
      development of anticancer agents. Two series of 1,5-diaryl substituted 1,2,3,4
      tetrazoles were concisely synthesized, using a palladium-catalyzed cross-coupling
      reaction, and identified as potent antiproliferative agents and novel tubulin
      polymerization inhibitors that act at the colchicine site. SAR analysis indicated
      that compounds with a 4-ethoxyphenyl group at the N-1 or C-5 position of the
      1,2,3,4-tetrazole ring exhibited maximal activity. Several of these compounds
      also had potent activity in inhibiting the growth of multidrug resistant cells
      overexpressing P-glycoprotein. Active compounds induced apoptosis through the
      mitochondrial pathway with activation of caspase-9 and caspase-3. Furthermore,
      compound 4l significantly reduced in vivo the growth of the HT-29 xenograft in a
      nude mouse model, suggesting that 4l is a promising new antimitotic agent with
      clinical potential.

PMID- 22136315
TI  - Morbidity-mortality and performance evaluation of Brahman calves from in vitro
      embryo production.
AB  - BACKGROUND: The use of bovine in vitro embryo production (IVP) increases the
      reproductive potential of genetically superior cows, enabling a larger scale of
      embryo production when compared with other biotechnologies. However, deleterious
      effects such as abnormal fetal growth, longer gestation period, increased birth
      weight, abortion, preterm birth and higher rates of neonatal mortality have been
      attributed to IVP. The aim of this study was to compare the influence of in vitro
      embryo production and artificial insemination (AI) on gestation length,
      complications with birth, birth weight, method of feeding colostrum, passive
      transfer of immunity, morbidity-mortality, and performance in Brahman calves.
      RESULTS: Whilst gestation length and birth weight were significantly increased in
      IVP-derived calves, no difference in weaning weight was observed between groups.
      The passive transfer of immunity (PT), was assessed in IVP (n = 80) and AI (n =
      20) groups 24 hours after birth by determination of gamma-glutamyl transferase
      (GGT) and gammaglobulin activity as well as by quantification of the
      concentration of total protein in serum. No differences in passive transfer or
      incidences of dystocia and diseases at weaning were observed between groups.
      Birth weight, method of feeding colostrum and dystocia were not correlated with
      PT in either group. CONCLUSIONS: In this study, in vitro embryo production did
      not affect the health status, development, or passive transfer of immunity in
      Brahman calves.

PMID- 22136316
TI  - Syntheses and crystal structures of the closo-borate M[B8H9] (M = [PPh4]+ and
      [N(n-Bu4)]+).
AB  - Protonation of M(2)[B(8)H(8)] with HCl or NEt(3).HCl resulted in M[B(8)H(9)] (M =
      [PPh(4)](+) or [N(n-Bu(4))](+)). The monoanion was isolated and characterized by
      (1)H, (1)H{(11)B}, (11)B, and (11)B{(1)H} NMR spectroscopy. The "protonated" form
      [B(8)H(9)](-) showed a dynamic behavior in solution, which was analyzed by NMR
      spectroscopy and compared with theoretical calculations. The structures of
      [B(8)H(9)](-) as well as [B(8)H(8)](2-) were determined by single-crystal X-ray
      diffraction.

PMID- 22136317
TI  - Outcomes of Japanese breast cancer patients treated with pre-operative and post
      operative anastrozole or tamoxifen.
AB  - The present study examined long-term efficacy outcomes in a subgroup of
      postmenopausal, estrogen receptor-positive Japanese breast cancer patients from
      the Pre-Operative "Arimidex" Compared with Tamoxifen trial, following pre
      operative (3 months) and post-operative (5 years) adjuvant treatment with either
      anastrozole or tamoxifen. Patients with large, potentially operable, locally
      advanced breast cancer were randomized to receive anastrozole (1 mg/day) plus
      tamoxifen placebo or tamoxifen (20 mg/day) plus anastrozole placebo pre
      operatively. After surgery at 3 months, patients continued on the same study
      medication as adjuvant therapy for up to 5 years or until recurrence, intolerable
      toxicity or withdrawal of patient consent. Recurrence-free survival and overall
      survival were measured from the date of randomization to the date of recurrence
      or death, whichever occurred first. Patients were monitored for adverse events
      throughout the study period and up to 30 days following administration of the
      last study medication. During post-operative adjuvant therapy, 4/48 (8%)
      anastrozole and 25/49 (51%) tamoxifen patients experienced recurrence. There was
      a significant difference in recurrence-free survival between the two groups
      (hazard ratio 0.14; 95% confidence interval 0.05-0.41; P = 0.0003). There was a
      significant increase in overall survival with anastrozole (0.21; 0.05-0.96; P =
      0.0436) and there were 2/48 (4%) and 10/49 (20%) deaths with anastrozole and
      tamoxifen, respectively. Most patients responding to pre-operative therapy
      remained recurrence-free. Sequential pre-operative/post-operative treatment with
      anastrozole resulted in lower recurrence and death rates, compared with
      tamoxifen.

PMID- 22136318
TI  - An approach to addressing governance from a health system framework perspective.
AB  - As countries strive to strengthen their health systems in resource constrained
      contexts, policy makers need to know how best to improve the performance of their
      health systems. To aid these decisions, health system stewards should have a good
      understanding of how health systems operate in order to govern them
      appropriately. While a number of frameworks for assessing governance in the
      health sector have been proposed, their application is often hindered by
      unrealistic indicators or they are overly complex resulting in limited empirical
      work on governance in health systems. This paper reviews contemporary health
      sector frameworks which have focused on defining and developing indicators to
      assess governance in the health sector. Based on these, we propose a simplified
      approach to look at governance within a common health system framework which
      encourages stewards to take a systematic perspective when assessing governance.
      Although systems thinking is not unique to health, examples of its application
      within health systems has been limited. We also provide an example of how this
      approach could be applied to illuminate areas of governance weaknesses which are
      potentially addressable by targeted interventions and policies. This approach is
      built largely on prior literature, but is original in that it is problem-driven
      and promotes an outward application taking into consideration the major health
      system building blocks at various levels in order to ensure a more complete
      assessment of a governance issue rather than a simple input-output approach.
      Based on an assessment of contemporary literature we propose a practical approach
      which we believe will facilitate a more comprehensive assessment of governance in
      health systems leading to the development of governance interventions to
      strengthen system performance and improve health as a basic human right.

PMID- 22136320
TI  - The insignificance of statistical significance.

PMID- 22136319
TI  - Sexually related behaviors as predictors of HPV vaccination among young rural
      women.
AB  - PURPOSE: To explore whether sexually related behaviors predict refusal of the
      human papillomavirus (HPV) vaccine among a sample of women aged 18-26 in
      Appalachian Kentucky. METHODS: Using a convenience sample, young women attending
      health clinics and a community college in southeastern Kentucky were recruited to
      participate in a Women's Health Study. After completing a questionnaire, women
      received a free voucher for the three-dose HPV vaccine series. Completion of dose
      one served as the outcome variable. RESULTS: Women with a history of an abnormal
      Pap test were almost two times more likely to decline the HPV vaccine (adjusted
      odds ratio [AOR] 1.91, 95% confidence interval [CI] 1.14-3.20, p=0.015), and
      women who reported they had never had a Pap test were four times more likely to
      decline the vaccine (AOR 4.02, 95% CI 1.13-14.32, p=0.032). Women engaging in
      mutual masturbation were nearly two times more likely to decline the free vaccine
      (AOR 1.91, 95% CI 1.17-3.10, p=0.009). Use of hormonal birth control showed a
      protective effect against refusal of the free HPV vaccine (AOR 0.593, 95% CI 0.44
      0.80, p=0.001). CONCLUSIONS: Among this sample of Appalachian women, those
      engaging in behaviors that increase their risk for HPV infection were more likely
      to refuse the vaccine. Conversely, those women engaging in protective health
      behaviors were more likely to accept the vaccine. These findings suggest that
      those women not being vaccinated may be the very group most likely to benefit
      from vaccination. Cervical cancer prevention programs need to be creative in
      efforts to reach young women most in need of the vaccine based on a higher
      profile of sexually related behaviors and the proxy measure of this risk (having
      an abnormal Pap test result).

PMID- 22136322
TI  - Determination of the optimal concentration of several selective drugs useful for
      generating multi-transgenic porcine embryonic fibroblasts.
AB  - Porcine embryonic fibroblasts (PEFs) are widely used as donor cells for somatic
      cell nuclear transfer (SCNT) in pigs. Transfection of PEFs with exogenous DNA is
      essential for producing genetically modified (GM; transgenic or knockout) pigs
      via SCNT. In this case, selectable markers are strictly required selecting and
      enriching stably transfected cells. The most frequently used selective drug for
      this purpose is a neomycin analogue (G418/geneticin); neo has been widely used as
      a selectable marker gene in the genomic manipulation of pigs. However, little is
      known about optimal concentrations of other selection drugs. This often hampers
      functional analysis of the porcine genome and development of individual GM pigs.
      This study explores the optimal concentrations of selective drugs, other than
      neomycin, that can be used for the selection of transfected PEFs. Porcine
      embryonic fibroblasts were incubated in media containing different concentrations
      of drugs for up to 10 days, to determine the optimal drug concentrations fatal
      for PEFs. The following concentrations were found to be optimal selective
      concentrations for use with PEFs: G418/geneticin, 400 MUg/ml; blasticidin S, 8
      MUg/ml; hygromycin B, 40 MUg/ml; puromycin, 2 MUg/ml; and zeocin, 800 MUg/ml.
      Repeated transfections with plasmids carrying selectable markers resulted in the
      generation of multidrug-resistant swine transfectants. Furthermore, these markers
      were found to be independent. The present information will be useful for the
      production of SCNT-mediated GM piglets that express multiple transgenes.

PMID- 22136321
TI  - Role of aldosterone on lung structural remodelling and right ventricular function
      in congestive heart failure.
AB  - BACKGROUND: The mechanisms of benefit of mineralocorticoid receptors antagonists
      in congestive heart failure (CHF) are still debated. We hypothesized that
      aldosterone contributes to pulmonary remodelling and right ventricular (RV)
      dysfunction associated with CHF by stimulation of lung myofibroblasts (MYFs)
      proliferation. METHODS: Rats with moderate to large myocardial infarcts (MI) and
      CHF were studied. Two weeks after MI, spironolactone 100 mg/kg/day (n = 21) or no
      treatment (n = 24) were given for 3 weeks and compared to sham (n = 8). RESULTS:
      Infarct size was similar by ultrasound and pathologic measures in both MI
      groups.The MI-untreated group developed important lung remodelling with nearly
      doubling of dry lung weight (p < 0.01), reduced left ventricular (LV) fractional
      shortening (16 +/- 2% vs. 53 +/- 1%; mean +/- SEM, p < 0.0001), pulmonary
      hypertension (RV systolic pressure: 40 +/- 3 mmHg vs. 27 +/- 1 mmHg, p < 0.01)
      and RV hypertrophy (RV/(LV + septum): 38 +/- 3% vs. 24 +/- 1%, p < 0.05).
      Spironolactone had no effect on these parameters and did not improve LV or RV
      performance (tricuspid annular plane systolic excursion and RV myocardial
      performance index) measured by echocardiography. CHF induced a restrictive
      respiratory syndrome with histological lung fibrosis: this was also unaffected by
      spironolactone. Finally, isolated lung MYFs did not proliferate after exposure to
      aldosterone. CONCLUSION: Aldosterone does not significantly contribute to
      pulmonary remodelling and RV dysfunction associated with CHF. Other mechanisms
      are responsible for the beneficial effects of spironolactone in CHF.

PMID- 22136323
TI  - Characterization of arabinoxylan/cellulose nanocrystals gels to investigate
      fluorescent probes mobility in bioinspired models of plant secondary cell wall.
AB  - Biomass from lignocellulose (LC) is a highly complex network of cellulose,
      hemicellulose, and lignin, which is considered to be a sustainable source of
      fuels, chemicals and materials. To achieve an environmental friendly and
      efficient LC upgrading, a better understanding of the LC architecture is
      necessary. We have devised some LC bioinspired model systems, based on
      arabinoxylan gels, in which mobility of dextrans and BSA grafted with FITC has
      been studied by FRAP. Our results indicate that the probes diffusion is more
      influenced by their hydrodynamic radius than by the gel mesh size. The addition
      of some cellulose nanocrystals (CNCs) decreases polymer chain mobility and has
      low effect on the probes diffusion, suggesting that the gels are better organized
      in the presence of CNCs, as shown by rheological measurements and scanning
      electronic microscopy observations. This demonstrates that the FRAP analysis can
      be a powerful tool to screen the architecture of LC model systems.

PMID- 22136324
TI  - Improved postprandial glycemic control in patients with type 2 diabetes from
      subcutaneous injection of insulin lispro with hyaluronidase.
AB  - BACKGROUND: Coinjection of hyaluronidase has been shown to accelerate insulin
      absorption in healthy volunteers and patients with type 1 diabetes mellitus. This
      study was undertaken to compare the postprandial glycemic response of patients
      with type 2 diabetes mellitus (T2DM) administered insulin lispro with and without
      recombinant human hyaluronidase (rHuPH20) and regular human insulin (RHI) with
      rHuPH20. METHODS: This double-blind three-way crossover study compared the
      insulin pharmacokinetics and glucodynamic response to a standardized liquid meal
      (80 g of carbohydrate) in 21 patients with T2DM who received subcutaneous
      injections of individually optimized doses of lispro+/-rHuPH20 and RHI+rHuPH20.
      The optimum dose (targeting postprandial glucose [PPG] of 70-140 mg/dL) of each
      preparation was selected by the investigator following a fixed-dose escalation
      procedure in three dose-finding meals. RESULTS: Co-injection of lispro+rHuPH20
      accelerated pharmacokinetics relative to lispro alone (time to peak insulin
      concentration, 43 vs. 74 min; P=0.0045) with increased exposure in the first hour
      (184% of control; P<0.0001) and reduced exposure after 2 h (67% of control;
      P=0.0001). These accelerated pharmacokinetics improved both total hyperglycemic
      excursions (area under the curve for 0-4 h >140 mg/dL, 56% of control; P=0.048)
      and hypoglycemic excursions (area under the curve for 0-8 h <70 mg/dL, 34% of
      control; P=0.033), allowing over three times as many patients to reach the
      American Diabetes Association's target of peak PPG <180 mg/dL without requiring
      glucose treatment for hypoglycemia. The mean optimum dose of lispro was reduced
      8% from 0.275 U/kg without rHuPH20 to 0.254 U/kg with rHuPH20 (P=0.04).
      RHI+rHuPH20 had responses and optimum doses comparable to insulin lispro alone.
      All insulin preparations were well tolerated. CONCLUSIONS: Lispro+rHuPH20
      provided superior control of glycemic excursion compared with lispro alone, with
      lower insulin requirements and reduced hypoglycemic excursions.

PMID- 22136325
TI  - Samarium iodide-mediated Reformatsky reactions for the stereoselective
      preparation of beta-hydroxy-gamma-amino acids: synthesis of isostatine and
      dolaisoleucine.
AB  - The synthesis of beta-hydroxy-gamma-amino acids via SmI(2)-mediated Reformatsky
      reactions of alpha-chloroacetyloxazolidinones with aminoaldehydes is reported.
      Diastereoselective coupling is demonstrated to depend on the absolute
      configuration of the Evans chiral auxiliary employed in the reaction, allowing
      erythro or threo products to be obtained selectively. The potential utility of
      the methodology is exemplified by the facile synthesis of biologically relevant N
      Boc-isostatine (2b) and N-Boc-dolaisoleucine (3c).

PMID- 22136326
TI  - Cardioprotective activity of standardized extract of Ficus racemosa stem bark
      against doxorubicin-induced toxicity.
AB  - CONTEXT: Ficus racemosa Linn. (Moraceae) bark is a rich source of phenolic
      compounds having diverse biological properties including antioxidant activity.
      The present study evaluated the cardioprotective activity of sequential acetone
      extract of Ficus racemosa bark against doxorubicin-induced cardiotoxicity in
      rats. MATERIALS AND METHODS: The extract was standardized by high-performance
      liquid chromatography (HPLC) and subjected to acute toxicological evaluation in
      mice. Cardiotoxicity was induced by administration of doxorubicin (10 mg kg(-1)
      i.v.) to the extract pretreated rats (250 and 500 mg kg(-1)) and compared with
      that of Arjuna, a standard cardiotonic. Biochemical parameters included CK-MB,
      LDH, AST, ALT, troponin I, thiobarbituric acid reactive substances (TBARS), and
      glutathione. RESULTS: The HPLC fingerprinting of the extract indicated the
      presence of bergenin (0.89%) and bergapten (0.07%). In an acute toxicity study,
      the extract at a dose of 2 g kg(-1) did not cause any adverse changes and no
      mortality was observed. Administration of doxorubicin significantly increased (p
      <= 0.05) serum levels of creatine kinase, lactate dehydrogenase, aspartate
      aminotransferase, and alanine aminotransferase, which were decreased to an extent
      of 68, 63, 41, and 65%, respectively, in extract pretreated group (500 mg kg(
      1)). Troponin I was undetected in control group, while it was found in serum of
      all the experimental groups. The extract pretreatment significantly decreased (p
      <= 0.05) TBARS and increased glutathione levels in serum and cardiac tissue.
      These observations were further substantiated by the histopathological studies.
      CONCLUSION: The acetone extract of F. racemosa bark possesses potential
      cardioprotective activity against doxorubicin-induced cardiotoxicity in rats by
      scavenging free radicals generated by the administration of the drug.

PMID- 22136329
TI  - Synthesis, structure, and magnetism of an f element nitrosyl complex,
      (C5Me4H)3UNO.
AB  - (C(5)Me(4)H)(3)U, 1, reacts with 1 equiv of NO to form the first f element
      nitrosyl complex (C(5)Me(4)H)(3)UNO, 2. X-ray crystallography revealed a 180
      degrees  U-N-O bond angle, typical for (NO)(1+) complexes. However, 2 has a
      1.231(5) A N?O distance in the range for (NO)(1-) complexes and a short 2.013(4)
      A U-N bond like the U?N bond of uranium imido complexes. Structural,
      spectroscopic, and magnetic data as well as DFT calculations suggest that
      reduction of NO by U(3+) has occurred to form a U(4+) complex of (NO)(1-) that
      has pi interactions between uranium 5f orbitals and NO pi* orbitals. These
      bonding interactions account for the linear geometry and short U-N bond. The
      complex displays temperature-independent paramagnetism with a magnetic moment of
      1.36 MU(B) at room temperature. Complex 2 reacts with Al(2)Me(6) to form the
      adduct (C(5)Me(4)H)(3)UNO(AlMe(3)), 3.

PMID- 22136331
TI  - 'Any body is better than nobody?' Ethical questions around recruiting and/or
      retaining health professionals in rural areas.
AB  - INTRODUCTION: The literature on recruiting and/or retaining health professionals
      in rural areas focuses primarily on the development of recruitment and retention
      strategies and assessing whether such strategies are effective. The objective of
      this article is to argue that it is important for all stakeholders involved in
      rural recruitment and/or retention processes to consider their decisions and
      actions from an ethics perspective. Recruitment and/or retention processes are
      not value neutral and it is important to understand their ethical dimensions.
      METHODS: From the literature, elements of the recruitment and/or retention
      strategies that have been employed were identified and organised in respect of
      levels of governance (namely, the levels of health system/government, community,
      and individual health professionals). The elements identified in these levels
      were subjected to analysis to identify their ethical dimensions and to determine
      whether a clash or complement of values arose at each level of governance or
      between governance levels. RESULTS: There is very little literature in this area
      that considers the ethical dimensions of rural recruitment and/or retention
      processes. However, all policies and practices have ethical dimensions that need
      to be identified and understood as they may have significant implications for
      recruitment and/or retention processes. CONCLUSIONS: This article recommends the
      application of an ethics perspective when reflecting on rural recruitment and/or
      retention strategies. The collective decisions of all involved in rural
      recruitment and/or retention processes may fundamentally influence the 'health'
      (broadly understood) of rural communities.

PMID- 22136330
TI  - Overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in visceral adipose
      tissue and portal hypercortisolism in non-alcoholic fatty liver disease.
AB  - BACKGROUND: The enzyme 11beta-hydroxysteroid-dehydrogenase type 1 (11beta-HSD1)
      catalyses the reactivation of intracellular cortisol. We explored the potential
      role of 11beta-HSD1 overexpression in visceral adipose tissue (VAT) in non
      alcoholic fatty liver disease (NAFLD) assessing sequential changes of enzyme
      expression, in hepatic and adipose tissue, and the occurrence of portal
      hypercortisolism in obese mice. 11beta-HSD1 expression was also assessed in
      tissues from obese patients undergoing bariatric surgery. METHODS: Peripheral and
      portal corticosterone levels and liver histology were assessed in ob/ob mice at
      two time points (8-12 weeks of age). 11beta-HSD1 tissue expression was assessed
      in by RT-pcr in ob/ob mice and in 49 morbidly obese patients. RESULTS: Portal
      corticosterone serum levels were higher in obese mice with a 26% decrease between
      8 and 12 weeks of age (controls: 78.3 +/- 19.7 ng/ml, 8-week-old ob/ob: 167.5 +/-
      14.5 ng/ml and 12-week-old ob/ob: 124.3 +/- 28 ng/ml, P < 0.05). No significant
      differences were found in peripheral corticosterone serum levels. Expression of
      11beta-HSD1 was lower in the liver [-45% at 8 weeks and -35% at 12-weeks (P =
      0.0001)] and highly overexpressed in VAT in obese mice, compared to controls (128
      fold higher in 8-week-old ob/ob and 41-fold higher in 12-week-old ob/ob, P <
      0.01). No significant differences were seen in the expression of 11beta-HSD1 in
      subcutaneous adipose tissue. In multivariate analysis, human 11beta-HSD1
      expression in VAT (OR: 1.385 +/- 1.010-1.910) was associated with NAFLD.
      CONCLUSION: Murine NAFLD is associated with portal hypercortisolism and11beta
      HSD1 overexpression in VAT. In humans, 11beta-HSD1 VAT expression was associated
      with the presence of NAFLD. Thus, local corticosteroid production in VAT may
      contribute to NAFLD pathogenesis.

PMID- 22136332
TI  - How to approach genome wars in sepsis?
AB  - Sepsis continues to pose a clear challenge as one of the most difficult and
      costly problems to treat and prevent. Sepsis is caused by systemic or localized
      infections that damage the integrity of microcirculation in multiple organs. The
      challenge of sepsis and its long-term sequelae was addressed by the National
      Institutes of Health National Heart Lung and Blood Institute Division of Blood
      Diseases and Resources. Defining sepsis as severe endothelial dysfunction
      syndrome that causes multiorgan failure in response to intravascular or
      extravascular microbial agents, the National Heart Lung and Blood Institute panel
      proposed the concept of genome wars as a platform for new diagnostic,
      therapeutic, and preventive approaches to sepsis.

PMID- 22136333
TI  - Decellularization of porcine corneas and repopulation with human corneal cells
      for tissue-engineered xenografts.
AB  - PURPOSE: To evaluate the potential use of decellularized porcine corneas (DPCs)
      as a carrier matrix for cultivating human corneal cells in tissue engineering.
      METHODS: Corneal cells were isolated from human corneoscleral rims. Porcine
      corneas were decellularized using hypotonic tris buffer, ethylene diamine tetra
      acetic acid (EDTA, 0.1%), aprotinin (10 KIU/ml) and 0.3% sodium dodecyl sulphate.
      Haematoxylin-eosin (HE) and 4,6-diamidino-2-phenylindole (DAPI) staining were
      performed to confirm removal of the corneal cells. Quantitative analysis was
      performed to determine levels of desoxyribonucleic acid (DNA) using DNA
      Purification Kit (Fermentas, St. Leon-Rot, Germany). Alcian blue staining was
      carried out to analyse the structure of the extracellular matrix (ECM). Corneal
      stromal cells were injected into the DPCs; limbal corneal epithelial cells and
      corneal endothelial cells were seeded onto the anterior and posterior surfaces of
      the DPCs, respectively. Evaluation was undertaken at days 14 and 30. The
      phenotypical properties of the cultivated corneal cells were investigated using
      Immunolocalization of type I collagen, keratocan, lumican, cytokeratin 3 (AE5)
      and type VIII collagen. RESULTS: Haematoxylin-eosin and DAPI staining showed
      efficient elimination of porcine corneal cells, whereas alcian blue confirmed
      gross preservation of the ECM. The quantitative analysis of the DNA content
      showed a significant reduction (mean before decellularization: 75.45 +/- 13.71
      ng/mg; mean after decellularization: 9.87 +/- 2.04 ng/mg, p < 0.001). All three
      types of corneal cells were efficiently cultured and expanded on the DPCs.
      CONCLUSIONS: Decellularized porcine corneas might serve as a potential scaffold
      for tissue engineering of the cornea, possibly providing xenogenic substrate for
      corneal transplantation.

PMID- 22136334
TI  - Anti-TNF agents and nail psoriasis: a single-center, retrospective, comparative
      study.
AB  - BACKGROUND: Anti-tumor necrosis factor (TNF) agents' effect on psoriatic nails is
      still under investigation. OBJECTIVE: To evaluate the therapeutic potentials of
      anti-TNF agents on psoriatic nails of patients suffering from moderate-to-severe
      plaque psoriasis. MATERIALS AND METHODS: A retrospective study was conducted
      based on the medical records of 12 patients treated with infliximab, 14 with
      adalimumab and 13 with etanercept in daily practice. The Nail Psoriasis Severity
      Index (NAPSI) was recorded at baseline, week 12, 24 and 48. RESULTS: At week 12,
      NAPSI was improved compared to baseline by 48.0% (range: 40.2-66.6%) with
      infliximab, 35.0% (range: 25.0-52.6%) with adalimumab and 41.7% (range: 39.5
      46.4%) with etanercept. At week 24, NAPSI was improved by 80.4% (range: 66.6
      90.2%) with infliximab, 70.2% (66.6-80.2%) with adalimumab and 76.1% (62.5-85.5%)
      with etanercept. At week 48, NAPSI was improved by 95.1% (range: 89.5-97.3%) with
      infliximab, 89.5% (75.0-94.8%) with adalimumab and 92.8% (84.3-96.0%) with
      etanercept. NAPSI percentage improvement was statistically significant across
      follow-up period (p = 0.000) for each anti-TNF treatment, as well as among
      treatments at all time points (week 12, p = 0.000; week 24, p = 0.001; week 48, p
      = 0.000). CONCLUSION: All anti-TNF agents result in a significant improvement of
      NAPSI score, with infliximab given the precedence and followed by etanercept and
      adalimumab.

PMID- 22136335
TI  - The role of the minimally invasive beating heart technique in reoperative valve
      surgery.
AB  - OBJECTIVE: We reviewed our experience to assess potential advantages of minimally
      invasive surgery without aortic clamping over conventional median sternotomy and
      cardioplegic arrest during reoperative valve surgery. METHODS: From August 2008
      to August 2010, 22 reoperative valve procedures were performed through a
      minimally invasive approach without aortic cross-clamping [no-clamp group (NCG)].
      Postoperative results were compared to a matched population in terms of sex, age,
      and type of surgery, and operated through median sternotomy with aortic cross
      clamping and cardioplegic arrest [clamp group (CG)]. RESULTS: We performed 17
      mitral valve replacements (MVRs), one mitral valve repair, one MVR associated to
      a tricuspid plasty (TVP), and three isolated TVP in both groups. Cardiopulmonary
      bypass (CPB) time was 166 and 163 minutes in NCG and CG, respectively. Intra
      aortic balloon pump was necessary in two (NCG) and three (CG) patients. Two
      patients died in both groups from multiorgan failure. Biochemical analysis showed
      no significant differences in perioperative lactate or creatine kinase-MB values.
      CONCLUSIONS: Redo valve surgery with an unclamped aorta is feasible, effective,
      and at least as safe as surgery using cardioplegic arrest. There was, however, no
      difference in biochemical or clinical outcomes from conventional surgery using
      aortic clamping and cardioplegic techniques.

PMID- 22136336
TI  - Synthesis, biological evaluation, and molecular modeling of chalcone derivatives
      as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatases
      (PtpA and PtpB).
AB  - Tuberculosis (TB) is a major infectious disease caused by  Mycobacterium
      tuberculosis  (Mtb). According to the World Health Organization (WHO), about 1.8
      million people die from TB and 10 million new cases are recorded each year.
      Recently, a new series of naphthylchalcones has been identified as inhibitors of
      Mtb protein tyrosine phosphatases (PTPs). In this work, 100 chalcones were
      designed, synthesized, and investigated for their inhibitory properties against
      MtbPtps. Structure-activity relationships (SAR) were developed, leading to the
      discovery of new potent inhibitors with IC(50) values in the low-micromolar
      range. Kinetic studies revealed competitive inhibition and high selectivity
      toward the Mtb enzymes. Molecular modeling investigations were carried out with
      the aim of revealing the most relevant structural requirements underlying the
      binding affinity and selectivity of this series of inhibitors as potential anti
      TB drugs.

PMID- 22136337
TI  - Genetic variant in CASP3 affects promoter activity and risk of esophageal
      squamous cell carcinoma.
AB  - Caspase-3 (CASP3) is the main executioner of apoptosis, mediating both extrinsic
      and intrinsic cell death signaling pathways, and is involved in tumor behaviors.
      In this study, we investigated the association of two regulatory variants in
      CASP3 and the risk of esophageal squamous cell carcinoma (ESCC) in 1026 cases and
      1270 healthy controls. Odds ratios (OR) and 95% confidence intervals (CI) were
      computed by logistic regression. The function of the CASP3 829 A>C polymorphism
      was examined by luciferase reporter assay and real-time PCR. A significant
      increased risk of ESCC was found for the CASP3 829 AC and CC genotypes with OR
      (95% CI), 1.53 (1.26-1.89) and 1.42 (1.11-1.82), respectively. When stratified by
      age and gender, the risk of ESCC was more significant in younger (<=57 years) and
      male individuals. No significantly changed risk of ESCC was related to 20541 C>T
      variant. Luciferase reporter assay showed 829 A>C variant dramatically reduced
      the transcriptional activity of luciferase reporter gene by over 95% in both
      KYSE30 and KYSE450 esophageal cancer cells. Remarkably, the transcriptional
      activity of the 829C-containing construct was much lower than the activity of the
      pGL3-basic construct, with over 85% reduction in both cell lines. Real-time PCR
      analyses showed that 829 AA genotype carriers had significantly higher RNA levels
      (0.015 +/- 0.00216, n = 24) than the 829 AC genotype carriers (0.00969 +/-
      0.00136, n = 36), and 829 CC genotype carriers (0.00663 +/- 0.00097, n = 20).
      These findings suggest that CASP3 829 A>C polymorphism may highly affect the
      function of caspase-3 and play an important role in the development of ESCC in
      Chinese populations.

PMID- 22136339
TI  - Recurrent uncomplicated urinary tract infections in women: a review.
AB  - Recurrent urinary tract infections most often present with symptoms of irritative
      voiding. In most cases, they are caused by reinfection with a previously isolated
      organism. Patients with one or more symptoms of uncomplicated recurrent urinary
      tract infection should undergo thorough examination and screening for underlying
      comorbidities that increase susceptibility. When frequent reinfections, empiric
      treatment relapse, persistent infections, or risk factors for complicated
      infections are encountered, patients may benefit from urodynamics, cystoscopy,
      renal ultrasound, intravenous urogram, or voiding cystourethrogram to evaluate
      for anatomic, functional, or metabolic abnormalities affecting the urinary tract
      (e.g., stones, stricture, obstruction, vesicoureteral reflux, lesions, detrusor
      underactivity). These patients may benefit from culture-guided empiric treatment
      and further evaluation by urology, nephrology, or infectious disease specialists.
      In patients with a history of uncomplicated urinary tract infections, empiric
      treatment guided by local antimicrobial resistance may efficiently treat a
      suspected recurrence. After successful treatment of the acute infection,
      postcoital prophylaxis, continuous prophylaxis, or self-start empiric treatment
      may be selected based on frequency of recurrent infections, temporal relation to
      intercourse, and patient characteristics. Ancillary measures such as probiotics,
      cranberry products, or local estrogen replacement may also be considered. This
      article will review the current definition, epidemiology, pathogenesis,
      diagnosis, work-up, treatment, treatment side effects, and prevention of
      recurrent urinary tract infections in women. A suggested algorithm for evaluation
      and treatment based on current literature is provided.

PMID- 22136340
TI  - Applying the Female Sexual Functioning Index to sexual minority women.
AB  - BACKGROUND: Available measurements of women's sexual function do not account for
      different sexual orientations; rather, instruments have been developed using
      heterosexual samples. The Female Sexual Functioning Index (FSFI) is a widely used
      instrument, applicable for sexually active or inactive women. We apply the FSFI
      to a sample of women who have or prefer women as sexual partners, defined as
      sexual minority women, and who vary with respect to their sexual activity.
      METHODS: A modified version of the FSFI was used in a sample of sexual minority
      women. Statistical analyses focused on examining associations between FSFI
      responses of no sexual activity and women's characteristics. RESULTS: Partner
      status and sexual frequency was significantly associated with reporting no sexual
      activity on the FSFI. A revised scoring of the FSFI allows for the use of this
      instrument among women who vary on sexual frequency and partner status, without
      biasing their scores towards sexual dysfunction. The desire subscale is
      independent of sexual frequency, partner status, and sexual orientation.
      CONCLUSIONS: The modified wording of the FSFI and its revised scoring allow for
      the use of this instrument among sexual minority women. A separate reporting of
      the desire subscale will generate reliable and valid assessments of sexual
      minority women's sexual functioning.

PMID- 22136338
TI  - Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a
      molecular perspective of postnatal normal spinal growth and the etiopathogenesis
      of AIS with consideration of a network approach and possible implications for
      medical therapy.
AB  - Genetic factors are believed to play an important role in the etiology of
      adolescent idiopathic scoliosis (AIS). Discordant findings for monozygotic (MZ)
      twins with AIS show that environmental factors including different intrauterine
      environments are important in etiology, but what these environmental factors may
      be is unknown. Recent evidence for common chronic non-communicable diseases
      suggests epigenetic differences may underlie MZ twin discordance, and be the link
      between environmental factors and phenotypic differences. DNA methylation is one
      important epigenetic mechanism operating at the interface between genome and
      environment to regulate phenotypic plasticity with a complex regulation across
      the genome during the first decade of life. The word exposome refers to the
      totality of environmental exposures from conception onwards, comprising factors
      in external and internal environments. The word exposome is used here also in
      relation to physiologic and etiopathogenetic factors that affect normal spinal
      growth and may induce the deformity of AIS. In normal postnatal spinal growth we
      propose a new term and concept, physiologic growth-plate exposome for the normal
      processes particularly of the internal environments that may have epigenetic
      effects on growth plates of vertebrae. In AIS, we propose a new term and concept
      pathophysiologic scoliogenic exposome for the abnormal processes in molecular
      pathways particularly of the internal environment currently expressed as
      etiopathogenetic hypotheses; these are suggested to have deforming effects on the
      growth plates of vertebrae at cell, tissue, structure and/or organ levels that
      are considered to be epigenetic. New research is required for chromatin
      modifications including DNA methylation in AIS subjects and vertebral growth
      plates excised at surgery. In addition, consideration is needed for a possible
      network approach to etiopathogenesis by constructing AIS diseasomes. These
      approaches may lead through screening, genetic, epigenetic, biochemical,
      metabolic phenotypes and pharmacogenomic research to identify susceptible
      individuals at risk and modulate abnormal molecular pathways of AIS. The
      potential of epigenetic-based medical therapy for AIS cannot be assessed at
      present, and must await new research derived from the evaluation of epigenetic
      concepts of spinal growth in health and deformity. The tenets outlined here for
      AIS are applicable to other musculoskeletal growth disorders including infantile
      and juvenile idiopathic scoliosis.

PMID- 22136341
TI  - The process evaluation of two interventions aimed at portion size in worksite
      cafeterias.
AB  - BACKGROUND:   In a previous study, the effectiveness of introducing a small meal
      in addition to the existing size and a proportional pricing strategy have been
      assessed in Dutch worksite cafeterias. To assess the degree of implementation and
      to inform the design of future interventions, the present study aimed to describe
      the process evaluation of both interventions. METHODS:   Process evaluation
      components from Baranowski and Stables, and Rogers (i.e. Recruitment,
      Maintenance, Context, Resources, Implementation, Exposure, Contamination, and
      Continued use) were chosen as a theoretical basis. The process evaluation
      involved qualitative (e.g. structured observations, semi-structured interviews)
      and quantitative data (e.g. consumer questionnaires) collected from 17
      intervention and eight control worksite cafeterias. RESULTS:   In all
      intervention cafeterias, two portion sizes were offered. The pricing instructions
      were followed in 13 intervention cafeterias. The cafeterias managers indicated
      that they did not consider offering large and small meals as being complex, risky
      or time-consuming to implement. Some managers perceived the consumer demand as
      high, others as (too) low. One year after the study had ended, nine of the
      intervention cafeterias had continued (at least partly) to follow the protocol.
      CONCLUSIONS:   Offering a smaller portion size in addition to the existing size,
      as well as proportional pricing, was generally implemented as prescribed by the
      protocol and can be considered promising in terms of continued use. However,
      additional efforts are needed to make the intervention more effective in
      motivating consumers to replace their large portion with a small portion.

PMID- 22136343
TI  - A social work perspective: attitudes toward end-of-life planning.
AB  - This research examined social workers' attitudes toward end-of-life planning and
      related factors in a cross-sectional study (N = 844). Data were gathered on
      completion of a health care proxy, personal comfort, training experiences of
      social workers, and demographics. Attitudes toward end-of-life planning were
      related to personal completion of the health care proxy, personal comfort, and
      years of social work experience. These measures remained significant in all steps
      of the regression, regardless of practice grouping (health and aging or other
      than health and aging), suggesting the relative importance of personal rather
      than professional aspects. Respondents in the health and aging fields are older
      than those in other than health and aging, underscoring concerns about workforce
      issues in the field of aging.

PMID- 22136342
TI  - Biological activities of histidine-rich peptides; merging biotechnology and
      nanomedicine.
AB  - Histidine-rich peptides are commonly used in recombinant protein production as
      purification tags, allowing the one-step affinity separation of the His-tagged
      proteins from the extracellular media or cell extracts. Genetic engineering makes
      feasible the post-purification His-tag removal by inserting, between the tag and
      the main protein body, a target site for trans-acting proteases or a self
      proteolytic peptide with regulatable activities. However, for technical ease, His
      tags are often not removed and the fusion proteins eventually used in this form.
      In this commentary, we revise the powerful biological properties of histidine
      rich peptides as endosomolytic agents and as architectonic tags in nanoparticle
      formation, for which they are exploited in drug delivery and other nanomedical
      applications. These activities, generally unknown to biotechnologists, can
      unwillingly modulate the functionality and biotechnological performance of
      recombinant proteins in which they remain trivially attached.

PMID- 22136344
TI  - Design of a rural diabetes self-directed care program.
AB  - This article describes a rural self-directed care program for adults with
      diabetes. The intervention consisted of coordinating with primary care clinics,
      six 2-hour facilitated educational peer groups, communication with physicians,
      referral tracking and follow-up, telephone support, and cooking demonstrations.
      The educators minimized lectures and they allowed content to emerge from
      participant questions and concerns. The program provided culturally tailored
      written educational materials. The author identifies theory and process issues
      for designing a diabetes self-directed care program in rural settings.

PMID- 22136345
TI  - Parent perceptions to promote a healthier lifestyle for their obese child.
AB  - Parents of children referred to a pediatric multidisciplinary weight-management
      clinic were queried regarding the importance of and their readiness to promote
      healthy lifestyle behaviors with their children and also regarding their
      confidence in their ability to adopt those changes. Among the 193 children's
      parents who completed a questionnaire (93.7% response), greater than 75% of
      respondents recognized the importance of healthy eating and physical activity,
      and many indicated feeling both confident and ready to make changes.
      Surprisingly, even among those not confident, parents also indicated they were
      ready to change their child's eating (p < .001). This study explores the
      discrepancy between parents indicating a high level of importance and readiness
      to promote healthy lifestyle behaviors but having less confidence that they would
      actually be able to enact change.

PMID- 22136346
TI  - Promoting and measuring family caregiver self-efficacy in caregiver-physician
      interactions.
AB  - This article describes the development of a 5-item scale that assesses family
      caregivers' self-efficacy in communicating with physicians about ill family
      members (Perceived Efficacy in Caregiver-Physician Interactions-PECPI) in the
      context of an evaluation study of an online training in health care communication
      skills for caregivers. A national sample of 197 self-identified family caregivers
      participated in an online webinar and completed a brief evaluation instrument
      before and immediately after the training. Results indicated that the webinar was
      effective in increasing perceived self-efficacy and self-reported knowledge about
      and level of preparation for medical visits. Principal component analysis
      indicates that the PECPI is unidimensional with a Cronbach's alpha of .91.

PMID- 22136347
TI  - Patterns of social support among lymphoma patients considering stem cell
      transplantation.
AB  - There is lack of literature addressing factors that influence the process of care
      for patients with hematological malignancies. We evaluated the forms of social
      support available for patients with relapsed lymphoma considering stem cell
      transplantation and examined the influence of support on treatment delay. Data
      were collected from 119 patients with relapsed lymphoma using a questionnaire to
      capture sociodemographic information and emotional, informational, and
      instrumental forms of social support. Sixty-four percent of the patients were
      married, 56% had children over 18 years of age, 43% were employed, and 72% had
      private health insurance. Family members formed a major source of emotional
      support (83%), while 47% of patients considered personal prayers to be important.
      While 79% of patients received clinical support from nurses, few received formal
      group support or formal peer support (6.7% and 1.7% respectively). Support from
      extended family and peer groups reduced the likelihood of treatment delays. The
      potential benefits of peer group support should be reinforced for patients
      considering transplantation given how infrequent this form of social support is
      utilized and its positive impact on the process of care. Future studies should
      test the impact of social support on health outcomes especially among the
      underserved population.

PMID- 22136348
TI  - Barriers impeding access to primary oral health care among farmworker families in
      Central Florida.
AB  - Oral health care is critical for farmworkers' families in Central Florida. There
      is little research regarding the access to primary oral health care, barriers,
      and behaviors of Mexican migrant families. Forty semi-structured interviews were
      conducted with parents who are farmworkers in order to understand the factors
      that impact dental service utilization. Other factors that were also examined
      related to parental decisions regarding visits to the dentist with their
      children. This study highlights the inconsistent and inadequate patterns of
      dental health care services available for women, men, and children of farmworkers
      in Central Florida.

PMID- 22136349
TI  - The perceptions of the personal and professional factors influencing social
      workers in Saudi hospitals: a qualitative analysis.
AB  - The perceptions of 10 social workers regarding the personal and professional
      characteristics influencing their practice at Saudi hospitals were examined using
      semi-structured interviews. A qualitative analysis employing a thematic approach
      informed by grounded theory was undertaken and produced three broad interrelated
      themes: "skills upgrading," "departmental support," and "personal experience in
      the workplace," which subsequently informed the development of the overarching
      theme of "personal and professional factors." The discussion illustrates social
      work practitioners are inhibited from effectively performing their roles. These
      include: (a) Deficiencies related to job training and professional skills
      updating where there is a lack of efficient and accessible inservice training
      programs, especially in relation to practical issues. Further, these perceptions
      relate to a lack of long-term educational opportunities that impact on individual
      practitioner's currency of skills, techniques and pedagogy enabling/disenabling
      him/her to excel at his/her job, (b) Obvious bureaucracy within the controlling
      hierarchy and difficulty with the dissemination of information between the social
      workers were perceived to detrimentally impact on a practitioner's ability to
      attend to one's work demands, and (c) Personal day to day work experiences,
      including counterproductive emotional feelings (high stress), increased
      dissatisfaction with the job, and ineffective communication within the workplace
      were seen as limiting the social workers' professional potential. This article
      will focus on how these themes were addressed in terms of qualitative interview
      data.

PMID- 22136351
TI  - Enantio- and diastereoselective organocatalytic alpha-alkylation of aldehydes
      with 3-substituted 2-(bromomethyl)acrylates.
AB  - The catalytic direct alpha-alkylation of aldehydes with 2-(bromomethyl)acrylates
      has been accomplished, giving rise to alpha-branched and functionalized aldehydes
      of high diastereo- and enantiopurity. The influence of the nature of the ester
      group of the acrylates in reaction stereoselectivity and especially in reactivity
      is investigated. Optimum conditions implicate the use of phenyl acrylates in
      conjunction with organocatalyst 8. Application of thus obtained adducts in
      synthesis is illustrated with a concise stereocontrolled preparation of
      trisubstituted cyclopentenes.

PMID- 22136352
TI  - Molecular structure and vibrational spectra of mixed MDyX4 (M = Li, Na, K, Rb,
      Cs; X = F, Cl, Br, I) vapor complexes: a computational and matrix-isolation
      infrared spectroscopic study.
AB  - The structures, energetic, and vibrational properties of MDyX(4) (M = Li, Na, K,
      Rb, Cs; X = F, Cl, Br, I) mixed alkali halide/dysprosium halide complexes have
      been investigated by a joint computational and experimental, matrix-isolation
      Fourier-transform infrared spectroscopic (MI-IR), study. According to our DFT
      computations for the complexes with heavier halides and alkali metals the ground
      state structure is the tridentate isomer; while at high temperatures the
      bidentate structural isomer dominates. The survey of various dissociation
      processes revealed the preference of the dissociation to neutral MX and DyX(3)
      fragments over ionic and radical dissociation products. Cationic complexes are
      considerably less stable at 1000 K than the neutral complexes, and they prefer to
      dissociate to M(+) + DyX(4)(*) fragments. The vapor species of selected mixtures
      of NaBr and CsBr with DyBr(3) and of CsI with DyI(3) in the temperature range 900
      1000 K have been isolated in krypton and xenon matrices and investigated by
      infrared spectroscopy. Besides the characteristic vibrational frequencies of the
      monomeric and dimeric alkali halide species and of the dysprosium trihalide
      molecules, certain signals indicated the formation of MDyX(4) (M = Na, Cs; X =
      Br, I) mixed complexes. Comparison with the computed vibrational and
      thermodynamic characteristics of the relevant species lead to the conclusion that
      these complexes appear in the vapor predominantly as the C(2v)-symmetry bidentate
      isomer. This is the first time that this structure was identified in an
      experimental vibrational spectroscopic study. The signals appearing upon
      performing a thermal anneal cycle were tentatively assigned to the double complex
      M(2)DyX(5) (M = Na, Cs; X = Br, I). A structure in which one alkali atom is bound
      to dysprosium by three and the other by two bridges is proposed for these double
      complexes.

PMID- 22136353
TI  - Ultrathin hydrogel films for rapid optical biosensing.
AB  - Novel biosensors have been designed by reporting an analyte-induced (de)swelling
      of a stimuli-responsive hydrogel (usually in a form of thin film) with a suitable
      optical transducer. These simple, inexpensive hydrogel biosensors are highly
      desirable, however, their practical applications have been hindered, largely
      because of their slow response. Here we show that quick response hydrogel sensors
      can be designed from ultrathin hydrogel films. By the adoption of layer-by-layer
      assembly, a simple but versatile approach, glucose-sensitive hydrogel films with
      thickness on submicrometer or micrometer scale, which is 2 orders of magnitude
      thinner than films used in ordinary hydrogel sensors, can be facilely fabricated.
      The hydrogel films can not only respond to the variation in glucose
      concentration, but also report the event via the shift of Fabry-Perot fringes
      using the thin film itself as Fabry-Perot cavity. The response is linear and
      reversible. More importantly, the response is quite fast, making it possible to
      be used for continuous glucose monitoring.

PMID- 22136354
TI  - Alterations in promoter methylation status of tumor suppressor HIC1, SFRP2, and
      DAPK1 genes in prostate carcinomas.
AB  - Hypermethylated genomic DNA is a common feature in tumoral tissues, although the
      prevalence of this modification remains poorly understood. We aimed to determine
      the frequency of five tumor suppressor (TS) genes in prostate cancer and the
      correlation between promoter hypermethylation of these genes and low and high
      grade of prostate carcinomas. A total of 30 prostate tumor specimens were
      investigated for promoter methylation status of TS hypermethylated in cancer 1
      (HIC1), death-associated protein kinase 1 (DAPK1), secreted frizzled-related
      protein 2 (SFRP2), cyclin-dependent kinase inhibitor 2A (p16), and O-6
      methylguanine-DNA methyltransferase (MGMT) genes by using bisulfite modifying
      method. A high frequency of promoter hypermethylation was found in HIC1 (70.9%),
      SFRP2 (58.3%), and DAPK1 (33.3%) genes in tumor samples that were examined. The
      current data show high frequency of hypermethylation changes in HIC1, SFRP2, and
      DAPK1 genes in prostate carcinomas of high Gleason Score (GS).

PMID- 22136355
TI  - Genomic organization and promoter cloning of the human X11alpha gene APBA1.
AB  - X11alpha is a brain specific multi-modular protein that interacts with the
      Alzheimer's disease amyloid precursor protein (APP). Aggregation of amyloid-beta
      peptide (Abeta), an APP cleavage product, is believed to be central to the
      pathogenesis of Alzheimer's disease. Recently, overexpression of X11alpha has
      been shown to reduce Abeta generation and to ameliorate memory deficit in a
      transgenic mouse model of Alzheimer's disease. Therefore, manipulating the
      expression level of X11alpha may provide a novel route for the treatment of
      Alzheimer's disease. Human X11alpha is encoded by the gene APBA1. As evidence
      suggests that X11alpha expression can be regulated at transcription level, we
      have determined the gene structure and cloned the promoter of APBA1. APBA1 spans
      over 244 kb on chromosome 9 and is composed of 13 exons and has multiple
      transcription start sites. A putative APBA1 promoter has been identified upstream
      of exon 1 and functional analysis revealed that this is highly active in neurons.
      By deletion analysis, the minimal promoter was found to be located between -224
      and +14, a GC-rich region that contains a functional Sp3 binding site. In
      neurons, overexpression of Sp3 stimulates the APBA1 promoter while an Sp3
      inhibitor suppresses the promoter activity. Moreover, inhibition of Sp3 reduces
      endogenous X11alpha expression and promotes the generation of Abeta. Our findings
      reveal that Sp3 play an essential role in APBA1 transcription.

PMID- 22136356
TI  - Frequent increased gene copy number and high protein expression of tRNA (cytosine
      5-)-methyltransferase (NSUN2) in human cancers.
AB  - NSUN2, also known as SAKI or MISU, is a methyltransferase which catalyses
      (cytosine-5-)-methylation of tRNA. The human NSUN2 gene is located on chromosome
      5p15.31-33. We show that NSUN2 gene copy number is increased in oral and
      colorectal cancers. Protein expression levels of NSUN2 were determined by
      immunoblot using novel polyclonal antibodies raised against a synthetic peptide
      corresponding to the C-terminal region of the protein. In most normal tissues,
      NSUN2 expression levels were extremely low. On the other hand, oral and
      colorectal cancers typically expressed high levels of NSUN2. The level of NSUN2
      was similar in interphase and mitotic cells, and immunohistochemical analysis
      demonstrated strong staining for NSUN2 in oral and colon cancer tissues when
      compared with normal tissues, providing a distinct diagnostic significance for
      NSUN2 in comparison with Ki-67, a widely used marker of actively proliferating
      cells. In addition, elevated protein expression of NSUN2 was confirmed by
      immunohistochemical analysis of various cancers including esophageal, stomach,
      liver, pancreas, uterine cervix, prostate, kidney, bladder, thyroid, and breast
      cancers. NSUN2 is regulated by Aurora-B, a newly developed molecular target for
      cancer therapy, leading us to propose that NSUN2 might become a valuable target
      for cancer therapy and a cancer diagnostic marker.

PMID- 22136357
TI  - Reliability of the Marlowe-Crowne social desirability scale in Ethiopia, Kenya,
      Mozambique, and Uganda.
AB  - BACKGROUND: Studies of HIV often use self-reported surveys to measure sexual
      knowledge, attitudes, and practices. However, the self-reported data are
      vulnerable to social desirability (SD), a propensity of individuals to report
      favorable responses. The Marlowe-Crowne Social Desirability Scale (MC-SDS) was
      developed as a measure of the effect of social desirability, but it has not been
      adapted for or used in Africa. This study aimed to apply the MC-SDS nested in an
      HIV behavioral intervention program and to measure its reliability in four
      African countries. METHODS: The MC-SDS was adapted based on consultations with
      local stakeholders and pilot tested in Ethiopia, Kenya, Mozambique, and Uganda.
      Trained interviewers administered the modified 28-item MC-SDS survey to 455 men
      and women (ages 15-24 years). The scores for the social desirability scales were
      calculated for all participants. An analysis of the internal consistency of
      responses was conducted using the Cronbach's alpha coefficient. Acceptable
      internal consistency was defined as an alpha coefficient of >= 0.70. RESULTS:
      Mean social desirability scores ranged from a low of 15.7 in Kenya to a high of
      20.6 in Mozambique. The mean score was 17.5 for Uganda and 20.6 for Mozambique.
      The Cronbach's alpha coefficients were 0.63 in Kenya, 0.66 in Mozambique, 0.70 in
      Uganda, and 0.80 in Ethiopia. CONCLUSIONS: The MC-SDS can be effectively adapted
      and implemented in sub-Saharan Africa. The reliability of responses in these
      settings suggest that the MC-SDS could be a useful tool for capturing potential
      SD in surveys of HIV related risk behaviors.

PMID- 22136359
TI  - Nitrogen-doped graphene quantum dots with oxygen-rich functional groups.
AB  - Graphene quantum dots (GQDs) represent a new class of quantum dots with unique
      properties. Doping GQDs with heteroatoms provides an attractive means of
      effectively tuning their intrinsic properties and exploiting new phenomena for
      advanced device applications. Herein we report a simple electrochemical approach
      to luminescent and electrocatalytically active nitrogen-doped GQDs (N-GQDs) with
      oxygen-rich functional groups. Unlike their N-free counterparts, the newly
      produced N-GQDs with a N/C atomic ratio of ca. 4.3% emit blue luminescence and
      possess an electrocatalytic activity comparable to that of a commercially
      available Pt/C catalyst for the oxygen reduction reaction (ORR) in an alkaline
      medium. In addition to their use as metal-free ORR catalysts in fuel cells, the
      superior luminescence characteristic of N-GQDs allows them to be used for
      biomedical imaging and other optoelectronic applications.

PMID- 22136358
TI  - Chemical composition, antimicrobial, and cytotoxicity studies on S. erianthum and
      S. macranthum essential oils.
AB  - CONTEXT: Solanum erianthum D. Don and Solanum macranthum Dunal (Solanaceae) are
      widely used in traditional medicine. The leaves act as an abortifacient and in
      particular to treat leucorrhoea, sores, and skin irritations. OBJECTIVE: This
      study was undertaken to characterize the volatile constituents of the leaf and
      fruit essential oils of S. erianthum and S. macranthum; their antimicrobial and
      in vitro cytotoxic bioassay against human breast and prostate tumor cells.
      METHODS: The volatile oils were obtained by hydrodistillation and analyzed for
      their constituents by gas chromatography-mass spectrometry (GC-MS). Minimum
      Inhibitory Concentrations (MIC) were determined using the microbroth dilution
      technique while the cytotoxic potentials were evaluated using the Cell Titre
      96((R)) AQ(ueous) Non-Radioactive Cell Proliferation Assay method. RESULTS:
      Solanum erianthum essential oils were characterized by the abundance of alpha
      terpinolene (17.8%), alpha-phellandrene (17.5%), p-cymene (15.7%) and beta-pinene
      (11.7%) in the leaves; alpha-humulene (23.1%), humulene epoxide II (20.0%),
      caryophyllene oxide (16.5%), methyl salicylate (11.8%) and beta-caryophyllene
      (10.9%) in the fruits. The leaf oil of S. macranthum consisted of (E)-phytol
      (29.0%), pentadecanal (28.1%) and pentadecane (7.7%) while the major fruit oil
      constituents were alpha-humulene (36.5%), beta-caryophyllene (17.8%), ethyl
      palmitate (9.4%), and methyl salicylate (8.2%). Solanum erianthum leaf volatile
      oil demonstrated potent inhibitory activity against Hs 578T and PC-3 human breast
      and prostate tumor cells respectively. In addition, the Solanum essential oils
      exhibited significant antimicrobial activity (19.5-625 ug/mL) on pathogens
      employed in the assay. CONCLUSION: The Solanum essential oils possess strong
      antimicrobial activity in addition to the potent cytotoxic potential of S.
      erianthum leaf oil against Hs 578T and PC-3 cells.

PMID- 22136360
TI  - A maxillofacial tumour after liver transplantation.

PMID- 22136361
TI  - Qualitative research and AAC: strong methods and new topics.

PMID- 22136362
TI  - Communication intervention in children with severe disabilities and multilingual
      backgrounds: perceptions of pedagogues and parents.
AB  - Increasing global population movement has resulted in a corresponding increase of
      children with severe and multiple disabilities and complex communication needs
      who at home are exposed to languages different from the language used at school.
      The aim of this study was to highlight facilitating as well as limiting factors
      for effective communication intervention for these children both in school and
      within the family. Based on observations, qualitative research interviews and
      analysis in the tradition of grounded theory the results indicate that the
      quality of parent-teacher-interaction is central to effective communication
      intervention and culturally sensitive use of communication aids. Challenges for
      teachers as well as parents to achieve a mutually satisfying interaction are
      addressed, and issues regarding the language use with children with severe
      disabilities and a multilingual and multicultural background and the inclusion of
      their parents in school based activities are discussed.

PMID- 22136363
TI  - Using a life course approach to explore how the use of AAC impacts on adult
      sibling relationships.
AB  - A life-course methodology was used to explore the relationship between four
      adults with moderate/severe cerebral palsy with complex communication needs who
      used AAC, and six of their non-disabled siblings. In-depth interview data were
      analyzed using a constructivist grounded-theory approach. Elder's life-course
      paradigm illuminated the importance of historical timing, social time, linked
      lives, and human agency to the development of communication strategies between
      siblings. Taking a life-course approach to studying issues related to individuals
      who use AAC assists understanding of how their family experiences and
      relationships change over time. This understanding is important, given the strong
      commitment by family members demonstrated in this study to supporting individuals
      who use AAC.

PMID- 22136364
TI  - Communication and AAC in the lives of adults with autism: the stories of their
      older parents.
AB  - The aim of this study was to explore the communication experiences, particularly
      those related to augmentative and alternative communication (AAC), of older
      parents who had an adult son or daughter with autism. A narrative analysis of in
      depth interviews with 16 older parents indicated that the majority had rarely
      spontaneously mentioned AAC or other communication interventions. Most did not
      express the need for such services. Yet, communication breakdown featured
      prominently in parents' narratives about interactions with their son or daughter.
      The quality of the communication between older parents and their offspring with
      autism constituted important sources of both gratification and strain in parents'
      roles as caregivers. Reasons for the current lack of communication interventions
      are discussed, along with implications for communication and AAC service
      provision.

PMID- 22136365
TI  - The challenges and benefits of using participant observation to understand the
      social interaction of adults with intellectual disabilities.
AB  - Observation methods have been used in both communication and interaction
      research. Qualitative interpretive approaches are rare where participants have
      complex communication needs. Issues for qualitative researchers utilizing
      participant observation research methods have been well documented, but a similar
      discussion is lacking where the participants are people with severe intellectual
      disability. Observational data collected from a study of adults with severe
      intellectual disabilities in interaction with their social network members were
      scrutinized to identify challenges and benefits of participant observation.
      Challenges identified include the consent process, changing roles, and researcher
      intrusion. The use of participant observation with adults with severe
      intellectual disabilities allows for unexpected insights and provides context and
      credence for other lines of inquiry. Participant observation may be useful with
      other groups of people.

PMID- 22136366
TI  - The storybook method: research feedback with young participants.
AB  - Children are valuable informants for social research; however, their
      participation presents additional ethical and practical challenges. Of these
      challenges, feedback to verify the researchers' interpretations drawn from
      children's data, and the dissemination of project findings to young participants,
      have proven difficult to overcome. In this paper, we outline the Storybook
      method, an approach to feedback in research with young children. In the example
      study, illustrations, interactive pop-ups, and third-person disclosure were used
      to aid children aged 7-9 years to overcome the power imbalance in interviews with
      adults. The Storybook method facilitated active participation in the validation
      process. Potential modifications of the method for use with older populations,
      including adults with intellectual disabilities, complex communication needs, and
      those requiring alternate access to written texts, are also explored.

PMID- 22136367
TI  - Parachute without a ripcord: the skydive of communication interaction.
AB  - Identifying and rating the outcomes of an intervention is not a new concept, but
      has gained impetus and currency with the emergence of evidence-based practice to
      support clinical decision making. In this paper, we present a metaphor as a
      unifying framework for the many different goals and outcomes that may come into
      focus across extended interventions with individuals who use aided communication.
      The metaphor is that of skydiving. We explore the value of this metaphor in
      understanding outcome measures for interventions, using analysis of interview
      data collected with adults who have used high-tech aided communication devices
      over many years.

PMID- 22136368
TI  - Influence of genomic ancestry on the distribution of SLCO1B1, SLCO1B3 and ABCB1
      gene polymorphisms among Brazilians.
AB  - The frequency distribution of SNPs and haplotypes in the ABCB1, SLCO1B1 and
      SLCO1B3 genes varies largely among continental populations. This variation can
      lead to biases in pharmacogenetic studies conducted in admixed populations such
      as those from Brazil and other Latin American countries. The aim of this study
      was to evaluate the influence of self-reported colour, geographical origin and
      genomic ancestry on distributions of the ABCB1, SLCO1B1 and SLCO1B3 polymorphisms
      and derived haplotypes in admixed Brazilian populations. A total of 1039 healthy
      adults from the north, north-east, south-east and south of Brazil were recruited
      for this investigation. The c.388A>G (rs2306283), c.463C>A (rs11045819) and
      c.521T>C (rs4149056) SNPs in the SLCO1B1 gene and c.334T>G (rs4149117) and
      c.699G>A (rs7311358) SNPs in the SLCO1B3 gene were determined by Taqman 5'
      nuclease assays. The ABCB1 c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and
      c.3435C>T (rs1045642) polymorphisms were genotyped using a previously described
      single-base extension/termination method. The results showed that genotype and
      haplotype distributions are highly variable among populations of the same self
      reported colour and geographical region. However, genomic ancestry showed that
      these associations are better explained by a continuous variable. The influence
      of ancestry on the distribution of alleles and haplotype frequencies was more
      evident in variants with large differences in allele frequencies between European
      and African populations. Design and interpretation of pharmacogenetic studies
      using these transporter genes should include genomic controls to avoid spurious
      conclusions based on improper matching of study cohorts from Brazilian
      populations and other highly admixed populations.

PMID- 22136369
TI  - Clinical guidelines for diagnosing and managing ocular manifestations in children
      with mucopolysaccharidosis.
AB  - The mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders
      characterized by the accumulation of glycosaminoglycans in several tissues and
      organs. This accumulation results in an array of clinical manifestations and
      premature death in severe cases. Ocular problems are very common in children with
      MPS and may involve the cornea, sclera, trabecular meshwork, retina, optic nerve
      and also the posterior visual pathways. The aims of this study are to give an
      overview of ocular problems in MPS and to provide clinical guidelines for
      paediatric ophthalmologists for early diagnosis and management of ocular
      manifestations in children with MPS. Diagnostic problems may arise in children
      with severe corneal clouding, hampering visualization of the fundus. Intraocular
      pressures may be falsely high, even leading to suspicion and unnecessary pressure
      lowering treatment. Simple interventions such as the use of prescription glasses
      or photochromatic glasses can considerably improve quality of life in children
      with MPS.

PMID- 22136370
TI  - Interrupted aortic arch in the adult.

PMID- 22136371
TI  - Urine sTREM-1 assessment in diagnosing sepsis and sepsis-related acute kidney
      injury.
AB  - The triggering receptor expressed on myeloid cells-1 (TREM-1) is an
      immunoreceptor whose role is to amplify the inflammatory response mediated by the
      engagement of Toll-like and NOD-like receptors. As the expression of TREM-1 is
      believed to be upregulated during infection, this protein has been studied as a
      sepsis biomarker. In the previous issue of Critical Care, Su and colleagues
      reported on the usefulness of urinary soluble TREM-1 in diagnosing sepsis and
      assessing its severity. Importantly, the authors describe, for the first time,
      that urinary soluble TREM-1 measurement is able to predict the development of
      sepsis-associated acute kidney injury (AKI). If these results were to be
      confirmed by larger studies, urinary soluble TREM-1 would possibly become a new
      biomarker for sepsis-associated AKI.

PMID- 22136372
TI  - Interleukin-6 in sepsis and capillary leakage syndrome.
AB  - Bacterial sepsis is one of the most frequent and dreaded causes of death in
      intensive care units. According to the current understanding of sepsis, bacterial
      components activate innate immune responses via pattern-recognition receptors
      that stimulate signaling pathways, thereby leading to activation of NF-kappaB and
      the release of cytokines, alarming the organism and coordinating appropriate
      defense mechanisms. The resulting "cytokine storm" not only restricts bacterial
      invasion; it also harms the host by triggering a hemodynamic collapse with a drop
      in blood pressure, which could lead to death. One of the cytokines released
      during sepsis is interleukin-6 (IL-6). Originally described as a B-cell
      stimulating factor, this cytokine has since been shown to have multiple
      additional functions. Interestingly, there is emerging evidence of IL-6 trans
      signaling in the pathogenesis of sepsis. We review recent findings and discuss
      whether therapeutic interference with IL-6 trans-signaling may be beneficial in
      this important clinical scenario.

PMID- 22136373
TI  - Opioid activity of spinally selective analogues of N-naphthoyl-beta-naltrexamine
      in HEK-293 cells and mice.
AB  - Using the selective mu-kappa agonist, N-naphthoyl-beta-naltrexamine 1, as the
      prototype ligand, a series of closely related naphthalene analogues were
      synthesized to study the chemical space around the naphthalene moiety in an
      effort to evaluate how receptor selectivity is affected by chemical modification.
      Nine analogues (2-10) of compound 1 were synthesized and tested on HEK-293 cells
      expressing homomeric and heteromeric opioid receptors, and in the mouse tail
      flick assay. It was found that a small change in structure produces profound
      changes in selectivity in this series. This is exemplified by the discovery that
      introduction of a 6-fluoro group transforms 1 from a selective mu-kappa
      heteromeric receptor agonist to a delta-preferring agonist 7. The in vivo studies
      reveal that many of the ligands are more potent spinally than supraspinally and
      devoid of tolerance.

PMID- 22136374
TI  - Antioxidant activity of some lichen metabolites.
AB  - Antioxidant activity of several classes of lichen metabolites were assessed in
      the in vitro superoxide radical (SOR), nitric oxide radical and 2,2-diphenyl-1
      picrylhydrazil radical scavenging assays. The despsides sekikaic acid and
      lecanoric acid showed promising antioxidant activity in SOR assay with IC50
      values of 82.0 +/- 0.3 umol and 91.5 +/- 2.1 umol, respectively, while the
      depsidone lobaric acid exhibited an IC50 value of 97.9 +/- 1.6 umol, all relative
      to the standard, propyl gallate (IC50 = 106.0 +/- 1.7 umol). One of the most
      abundant mononuclear phenolic compounds, methyl-beta-orcinol carboxylate was
      found to be a potent NO scavenger (IC50 = 84.7 +/- 0.1 umol), compared to the
      standard rutin (IC50 = 86.8 +/- 1.9 umol).

PMID- 22136375
TI  - Fine needle aspiration cytology of a spindle epithelial tumour with thymus-like
      differentiation (SETTLE) occurring in the thyroid.

PMID- 22136376
TI  - Radiation techniques for acromegaly.
AB  - Radiotherapy (RT) remains an effective treatment in patients with acromegaly
      refractory to medical and/or surgical interventions, with durable tumor control
      and biochemical remission; however, there are still concerns about delayed
      biochemical effect and potential late toxicity of radiation treatment, especially
      high rates of hypopituitarism. Stereotactic radiotherapy has been developed as a
      more accurate technique of irradiation with more precise tumour localization and
      consequently a reduction in the volume of normal tissue, particularly the brain,
      irradiated to high radiation doses. Radiation can be delivered in a single
      fraction by stereotactic radiosurgery (SRS) or as fractionated stereotactic
      radiotherapy (FSRT) in which smaller doses are delivered over 5-6 weeks in 25-30
      treatments. A review of the recent literature suggests that pituitary irradiation
      is an effective treatment for acromegaly. Stereotactic techniques for GH
      secreting pituitary tumors are discussed with the aim to define the efficacy and
      potential adverse effects of each of these techniques.

PMID- 22136377
TI  - Long-term survival in patients with peripheral T-cell non-Hodgkin lymphomas after
      allogeneic hematopoietic stem cell transplant.
AB  - Peripheral T-cell non-Hodgkin lymphomas (T-NHL) are rare diseases, with a worse
      prognosis compared to their B-cell counterparts. Allogeneic hematopoietic stem
      cell transplant may have a role in the treatment of relapsed/refractory disease
      or high-risk histologies in the upfront setting. However, there is limited
      information on the efficacy of allogeneic transplant for these diseases, as well
      as what factors may predict outcomes. We therefore performed a retrospective
      study of 34 patients who received an allogeneic transplant for the treatment of T
      NHL at a single center between 1 January 1992 and 31 December 2009. The median
      follow-up for survivors was 45 months (range 9-160 months). The 2-year overall
      survival (OS) was 0.61 (95% confidence interval [CI]: 0.43-0.75) with a plateau
      at 28 months. Ki-67 expression <= 25% was predictive of improved OS (p < 0.01),
      and transplant in complete remission was predictive of a decreased cumulative
      incidence of events (p = 0.04). Three patients received a donor leukocyte
      infusion, and two patients demonstrated a response, supporting a graft-versus
      lymphoma effect. These data demonstrate that allogeneic transplant is a viable
      option for the treatment of T-NHL and merits prospective evaluation.

PMID- 22136378
TI  - Salvage chemotherapy and autologous stem cell transplant in primary refractory
      diffuse large B-cell lymphoma: outcomes and prognostic factors.
AB  - Patients with primary refractory diffuse large B-cell lymphoma (REF DLBCL:
      progression on or within 3 months of completion of primary therapy) sensitive to
      salvage chemotherapy undergo autologous stem cell transplant (ASCT). We conducted
      a retrospective review of 111 patients with REF DLBCL treated between 1999 and
      2007. Primary treatment consisted of cyclophosphamide, adriamycin, vincristine
      and prednisone (CHOP; 66%) and rituximab with CHOP (R-CHOP; 33%); 14% received
      involved field radiation. The response rate (RR) to first salvage chemotherapy
      was 23% (RR by regimen: dexamethasone, cytosine arabinoside and cisplatin [DHAP]
      15%, etoposide, Solu-Medrol, cytosine arabinoside and cisplatin [ESHAP] 36%, and
      gemcitabine, dexamethasone and cisplatin [GDP] 45%); 25% (n = 28) of patients
      underwent ASCT. With a median follow-up of 5.9 months (range 1-94), the median
      progression-free and overall survival from primary treatment failure was 3 and 10
      months, respectively. Outcomes in patients with REF DLBCL after CHOP or R-CHOP
      appear equally poor. Second-generation platinum-containing regimens (ESHAP, GDP)
      may be superior to DHAP in this setting. Novel, prospectively evaluated treatment
      approaches should be pursued in REF DLBCL.

PMID- 22136379
TI  - Anti-Hu-associated paraneoplastic limbic encephalitis in Hodgkin lymphoma.

PMID- 22136380
TI  - Electronic detection of lectins using carbohydrate-functionalized nanostructures:
      graphene versus carbon nanotubes.
AB  - Here we investigated the interactions between lectins and carbohydrates using
      field-effect transistor (FET) devices comprised of chemically converted graphene
      (CCG) and single-walled carbon nanotubes (SWNTs). Pyrene- and porphyrin-based
      glycoconjugates were functionalized noncovalently on the surface of CCG-FET and
      SWNT-FET devices, which were then treated with 2 MUM nonspecific and specific
      lectins. In particular, three different lectins (PA-IL, PA-IIL, and ConA) and
      three carbohydrate epitopes (galactose, fucose, and mannose) were tested. The
      responses of 36 different devices were compared and rationalized using computer
      aided models of carbon nanostructure/glycoconjugate interactions. Glycoconjugate
      surface coverage in addition to one-dimensional structures of SWNTs resulted in
      optimal lectin detection. Additionally, lectin titration data of SWNT- and CCG
      based biosensors were used to calculate lectin dissociation constants (K(d)) and
      compare them to the values obtained from the isothermal titration
      microcalorimetry technique.

PMID- 22136381
TI  - Selective inhibition of nuclear factor-kappaB by nuclear factor-kappaB essential
      modulator-binding domain peptide suppresses the metastasis of highly metastatic
      oral squamous cell carcinoma.
AB  - Nuclear factor-kappaB (NF-kappaB) activation contributes to the development of
      metastasis, thus leading to a poor prognosis in many cancers, including OSCC.
      However, little in vivo experimental data are available about the effects of NF
      kappaB inhibition on OSCC metastasis. OSCC sublines were established from a GFP
      expressing parental cell line, GSAS, and designated GSAS/N3 and N5 according to
      the in vivo passage number after cervical lymph node metastasis by a serial
      orthotopic transplantation model. In vitro migration and invasion were assessed
      in these cells, and the NF-kappaB activities and expression of NF-kappaB
      regulated metastasis-related molecules were also examined. In in vivo
      experiments, the metastasis and survival of tumor-engrafted mice were monitored.
      Furthermore, the effects of a selective NF-kappaB inhibitor, NEMO-binding domain
      (NBD) peptide, on metastasis in GSAS/N5-engrafted mice were assessed, and
      engrafted tongue tumors were immunohistochemically examined. Highly metastatic
      GSAS/N3 and N5 cells showed an enhanced NF-kappaB activity, thus contributing to
      increased migration, invasion, and a poor prognosis compared with the parent
      cells. Furthermore, the expression levels of NF-kappaB-regulated metastasis
      related molecules, such as fibronectin, beta1 integrin, MMP-1, -2, -9, and -14,
      and VEGF-C, were upregulated in the highly metastatic cells. The NBD peptide
      suppressed metastasis and tongue tumor growth in GSAS/N5-inoculated mice, and was
      accompanied by the downregulation of the NF-kappaB-regulated metastasis-related
      molecules in engrafted tongue tumors. Our results suggest that the selective
      inhibition of NF-kappaB activation by NBD peptide may provide an effective
      approach for the treatment of highly metastatic OSCC.

PMID- 22136383
TI  - Glycosidation of thioglycosides in the presence of bromine: mechanism,
      reactivity, and stereoselectivity.
AB  - Elaborating on previous studies by Lemieux for highly reactive "armed" bromides,
      we discovered that beta-bromide of the superdisarmed (2-O-benzyl-3,4,6-tri-O
      benzoyl) series can be directly obtained from the thioglycoside precursor. When
      this bromide is glycosidated, alpha-glycosides form exclusively; however, the
      yields of such transformations may be low due to the competing anomerization into
      alpha-bromide that is totally unreactive under the established reaction
      conditions.

PMID- 22136382
TI  - Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells
      to TRAIL-induced apoptosis.
AB  - BACKGROUND: Dysregulation of many apoptotic related genes and androgens are
      critical in the development, progression, and treatment of prostate cancer. The
      differential sensitivity of tumour cells to TRAIL-induced apoptosis can be
      mediated by the modulation of surface TRAIL receptor expression related to
      androgen concentration. Our previous results led to the hypothesis that
      downregulation of TRAIL-decoy receptor DcR2 expression following androgen
      deprivation would leave hormone sensitive normal prostate cells vulnerable to the
      cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested
      this hypothesis under pathological conditions by exploring the regulation of
      TRAIL-induced apoptosis related to their death and decoy receptor expression, as
      also to hormonal concentrations in androgen-sensitive human prostate cancer,
      LNCaP, cells. RESULTS: In contrast to androgen-insensitive PC3 cells, decoy
      (DcR2) and death (DR5) receptor protein expression was correlated with hormone
      concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen
      sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL
      mediated apoptosis related to androgen concentration in LNCaP cells. CONCLUSIONS:
      The data support the hypothesis that hormone modulation of DcR2 expression
      regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death
      induction in apoptosis-resistant hormone-sensitive tumour cells from prostate
      cancer. TRAIL action and DcR2 expression modulation are potentially of clinical
      value in advanced tumour treatment.

PMID- 22136384
TI  - Structural determinants for rCNT2 sorting to the plasma membrane of polarized and
      non-polarized cells.
AB  - rCNT2 (rat concentrative nucleoside transporter 2) (Slc28a2) is a purine
      preferring concentrative nucleoside transporter. It is expressed in both non
      polarized and polarized cells, where it is localized in the brush border
      membrane. Since no information about the domains implicated in the plasma
      membrane sorting of rCNT2 is available, the present study aimed to identify
      structural and functional requirements for rCNT2 trafficking. The comprehensive
      topological mapping of the intracellular N-terminal tail revealed two main
      features: (i) a glutamate-enriched region (NPGLELME) between residues 21 and 28
      that seems to be implicated in the stabilization of rCNT2 in the cell surface,
      since mutagenesis of these conserved glutamates resulted in enhanced endocytosis;
      and (ii) mutation of a potential protein kinase CK2 domain that led to a loss of
      brush border-specific sorting. Although the shortest proteins assayed (rCNT2
      74AA, -48AA and -37AA) accumulated intracellularly and lost their brush border
      membrane preference, they were still functional. A deeper analysis of CK2
      implication in CNT2 trafficking, using a CK2-specific inhibitor [DMAT (2
      dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)] and other complementary
      mutations mimicking the negative charge provided by phosphorylation (S46D and
      S46E), demonstrated an effect of this kinase on rCNT2 activity. In summary, the N
      terminal tail of rCNT2 contains dual sorting signals. An acidic region is
      responsible for its proper stabilization at the plasma membrane, whereas the
      putative CK2 domain (Ser(46)) is implicated in the apical sorting of the
      transporter.

PMID- 22136385
TI  - Profiling of antibody production against xenograft-released proteins by protein
      microarrays discovers prostate cancer markers.
AB  - This study describes a novel xenograft-based biomarker discovery platform and
      proves its usefulness in the discovery of serum markers for prostate cancer. By
      immunizing immuno-competent mice with serum from nude mice bearing prostate
      cancer xenografts, an antibody response against xenograft-derived antigens was
      elicited. By probing protein microarrays with serum from immunized mice, several
      prostate cancer-derived antigens were identified, of which a subset was
      successfully retrieved in serum from mice bearing prostate cancer xenografts and
      prevalidated in human serum samples of prostate cancer patients. Among the
      discovered and validated proteins were the members of the TAM receptor family
      (TYRO3, AXL, and MERTK), ACY1, and PSMA1. In conclusion, this novel method allows
      for the identification of low abundant cancer-derived serum proteins,
      circumventing dynamic range and host-response issues in standard patient cohort
      proteomics comparisons.

PMID- 22136386
TI  - Phosphonium-containing polyelectrolytes for nonviral gene delivery.
AB  - Nonviral gene therapy focuses intensely on nitrogen-containing macromolecules and
      lipids to condense and deliver DNA as a therapeutic for genetic human diseases.
      For the first time, DNA binding and gene transfection experiments compared
      phosphonium-containing macromolecules with their respective ammonium analogs.
      Conventional free radical polymerization of quaternized 4-vinylbenzyl chloride
      monomers afforded phosphonium- and ammonium-containing homopolymers for gene
      transfection experiments of HeLa cells. Aqueous size exclusion chromatography
      confirmed similar absolute molecular weights for all polyelectrolytes. DNA gel
      shift assays and luciferase expression assays revealed phosphonium-containing
      polymers bound DNA at lower charge ratios and displayed improved luciferase
      expression relative to the ammonium analogs. The triethyl-based vectors for both
      cations failed to transfect HeLa cells, whereas tributyl-based vectors
      successfully transfected HeLa cells similar to Superfect demonstrating the
      influence of the alkyl substituent lengths on the efficacy of the gene delivery
      vehicle. Cellular uptake of Cy5-labeled DNA highlighted successful cellular
      uptake of triethyl-based polyplexes, showing that intracellular mechanisms
      presumably prevented luciferase expression. Endocytic inhibition studies using
      genistein, methyl beta-cyclodextrin, or amantadine demonstrated the caveolae
      mediated pathway as the preferred cellular uptake mechanism for the delivery
      vehicles examined. Our studies demonstrated that changing the polymeric cation
      from ammonium to phosphonium enables an unexplored array of synthetic vectors for
      enhanced DNA binding and transfection that may transform the field of nonviral
      gene delivery.

PMID- 22136387
TI  - Predictors of referral uptake in children with disabilities in Bangladesh-
      exploring barriers as a first step to improving referral provision.
AB  - PURPOSE: Making services available to children with disabilities in low- and
      middle-income countries does not guarantee their use. This study aims to identify
      factors associated with the uptake of referrals in order to investigate barriers
      to service use. METHODS: Children with impairments identified in two districts of
      Bangladesh were invited to attend screening camps where their condition was
      confirmed; they were provided with referrals for rehabilitation and treatment
      services. Predictors of referral uptake were identified using logistic
      regression. RESULTS: Overall referral uptake was 47%, 32% in Sirajganj and 61% in
      Natore. There was no association between age or gender and referral uptake.
      Factors predictive of referral uptake were higher income in Sirajganj (OR=2.6
      95%CI 1.4-5.0), and the districts combined (OR=1.6 95%CI 1.1-2.1); maternal
      literacy in Natore (OR=1.6 95%CI 1.0-2.5); and epilepsy in all three models
      (Sirajganj: OR=2.6 95%CI 1.7-4.0; Natore: OR=13.5 95%CI 6.5-28.3; Combined:
      OR=4.6 95%CI 3.3-6.5). Physical impairment was associated with increased odds of
      uptake in Sirajganj and in the combined model (OR=2.7 95%CI 1.8-4.1; OR=3.34
      95%CI 2.2-5.2). CONCLUSIONS: Even when some logistical and financial assistance
      is available, children with impairment from low-income families may require
      additional support to take up referrals. There may be greater willingness to
      accept treatment that is locally provided, such as medication for epilepsy or
      therapy at village level.

PMID- 22136388
TI  - Guidelines on acute gastroenteritis in children: a critical appraisal of their
      quality and applicability in primary care.
AB  - BACKGROUND: Reasons for poor guideline adherence in acute gastroenteritis (AGE)
      in children in high-income countries are unclear, but may be due to inconsistency
      between guideline recommendations, lack of evidence, and lack of generalizability
      of the recommendations to general practice. The aim of this study was to assess
      the quality of international guidelines on AGE in children and investigate the
      generalizability of the recommendations to general practice. METHODS: Guidelines
      were retrieved from websites of professional medical organisations and websites
      of institutes involved in guideline development. In addition, a systematic search
      of the literature was performed. Articles were selected if they were a guideline,
      consensus statement or care protocol. RESULTS: Eight guidelines met the inclusion
      criteria, the quality of the guidelines varied. 242 recommendations on diagnosis
      and management were found, of which 138 (57%) were based on evidence.There is a
      large variety in the classification of symptoms to different categories of
      dehydration. No signs are generalizable to general practice.It is consistently
      recommended to use hypo-osmolar ORS, however, the recommendations on ORS-dosage
      are not evidence based and are inconsistent. One of 14 evidence based
      recommendations on therapy of AGE is based on outpatient research and is
      therefore generalizable to general practice. CONCLUSIONS: The present study shows
      considerable variation in the quality of guidelines on AGE in children, as well
      as inconsistencies between the recommendations. It remains unclear how to asses
      the extent of dehydration and determine the preferred treatment or referral of a
      young child with AGE presenting in general practice.

PMID- 22136389
TI  - Adjacent-level biomechanics after single versus multilevel cervical spine fusion.
AB  - OBJECT: Previous studies have demonstrated that patients with spinal fusion are
      at greater risk for adjacent-segment disease and require additional surgery. It
      has been postulated that excessive motion of a given motion segment unit (MSU)
      leads to an increased risk of disc degeneration. It is the authors' hypothesis
      that a greater increase in adjacent-segment motion will be observed following a 2
      level versus a single-level anterior cervical discectomy and instrumented fusion
      (ACDF). Therefore, they undertook this study to determine the effect of single
      level versus 2-level ACDF on the biomechanics of adjacent MSUs. METHODS: Ten
      fresh-frozen human cervical spines were used in this study. The specimens were
      potted at C-4 and T-1 and tested in flexion and extension. Range of motion (ROM)
      was 30 degrees  of flexion and 15 degrees  of extension at a maximum load of 50
      N. The specimens were tested intact and then were randomized into 2 groups of 5
      specimens each. Group 1 underwent a single-level ACDF at the C5-6 level first,
      and Group 2 underwent the procedure at the C6-7 level. After testing, both groups
      had the fusion extended to include the C5-7 levels, and the testing was repeated.
      Changes in overall ROM, stiffness, and segmental motion were calculated and
      statistically analyzed using a paired Student t-test. RESULTS: An increase in
      sagittal ROM of 31.30% above (p = 0.012) and 33.88% below (p = 0.066) the fused
      MSU was found comparing a 2-level with a 1-level ACDF. The overall stiffness of
      the entire spinal construct increased 37.34% (p = 0.051) in extension and 30.59%
      (p = 0.013) in flexion as the second fusion level was added. As expected, the
      overall sagittal ROM of the entire spinal construct decreased by 13.68% (p =
      0.0014) with a 2-level compared with a 1-level fusion. CONCLUSIONS: This study
      has shown that the biomechanics at adjacent levels to a cervical spine fusion are
      altered and that there is increased adjacent-segment motion at the levels above
      and below, after a 2-level compared with a 1-level ACDF.

PMID- 22136390
TI  - Differences between soft-disc herniation and spondylosis in cervical
      arthroplasty: CT-documented heterotopic ossification with minimum 2 years of
      follow-up.
AB  - OBJECT: Cervical arthroplasty is a valid option for patients with single-level
      symptomatic cervical disc diseases causing neural tissue compression, but
      postoperative heterotopic ossification (HO) can limit the mobility of an
      artificial disc. In the present study the authors used CT scanning to assess HO
      formation, and they investigated differences in radiological and clinical
      outcomes in patients with either a soft-disc herniation or spondylosis who
      underwent cervical arthroplasty. METHODS: Medical records, radiographs, and
      clinical evaluations of consecutive patients who underwent single-level cervical
      arthroplasty were reviewed. Arthroplasty was performed using the Bryan disc. The
      patients were divided into a soft-disc herniation group and a spondylosis group.
      Clinical outcomes were measured using the visual analog scale (VAS) for neck and
      arm pain and the Neck Disability Index (NDI), whereas HO grading was determined
      by studying CT scans. Radiological and clinical outcomes were analyzed, and the
      minimum follow-up duration was 24 months. RESULTS: Forty-seven consecutive
      patients underwent a single-level cervical arthroplasty. Forty patients (85.1%)
      had complete radiological evaluations and clinical follow-up of more than 2
      years. Patients were divided into 1 of 2 groups: soft-disc herniation (16 cases)
      and the spondylosis group (24 cases). Their mean age was 45.51 +/- 11.12 years.
      Sixteen patients (40%) were female. Patients in the soft-disc herniation group
      were younger than those in the spondylosis group, but the difference was not
      statistically significant (42.88 vs 47.26, p = 0.227). The mean follow-up
      duration was 38.83 +/- 9.74 months. Sex, estimated blood loss, implant size, and
      perioperative NSAID prescription were not significantly different between the
      groups (p = 0.792, 0.267, 0.581, and 1.000, respectively). The soft-disc
      herniation group had significantly less HO formation than the spondylosis group
      (1 HO [6.25%] vs 14 Hos [58.33%], p = 0.001). Almost all artificial discs in both
      groups remained mobile (100% and 95.8%, p = 0.408). The clinical outcomes were
      not significantly different between the groups at all postoperative time points
      of evaluation, and clinical improvements were also similar. CONCLUSIONS: Clinical
      outcomes of single-level cervical arthroplasty for soft-disc herniation and
      spondylosis were similar 3 years after surgery. There was a significantly higher
      rate of HO formation in patients with spondylosis than in those with a soft-disc
      herniation. The mobility of the artificial disc is maintained, but the long-term
      effects of HO and its higher frequency in spondylotic cases warrant further
      investigation.

PMID- 22136391
TI  - Validation of a simple computerized tool for measuring spinal and pelvic
      parameters.
AB  - OBJECT: Recent studies have emphasized measuring the sagittal vertical axis (SVA)
      and pelvic parameters (pelvic incidence, sacral slope, and pelvic tilt) when
      evaluating spinal disorders. An accurate and reproducible measurement is
      important for a reliable result. Although computerized measurement is more
      consistent than manual measurement, computerized measurement requires an
      expensive software program, the need to transfer images to a workstation, and
      additional education for users. An inexpensive and convenient computerized
      measurement program is desirable and necessary. The object of this study was to
      propose a computerized tool for measuring spinal and pelvic parameters and to
      evaluate the efficacy of this new tool compared with manual measurement. METHODS:
      The authors devised a tool that provides computerized measurements of the SVA and
      pelvic parameters in a picture archiving and communication system (PACS) without
      transferring images to another program. This tool was created by merging
      functions in the PACS. The resulting tool is easy to implement by merging
      functions (indicate the center of 2 points, plot a vertical and a horizontal line
      from a point, and measure the angles between lines) in any image viewer. The tool
      was made into icons on a toolbar in the PACS. Measurements of distance and angle
      were computerized by identifying crucial points after selecting the icon. For
      SVA, 4 points were identified around each corner of the C-7 body and a fifth
      point at the superior/posterior corner of the S-1 body. For pelvic parameters, 4
      points were identified at the centers of each femoral head and at the
      anterior/superior and posterior/superior corners of S-1. Thirty-three whole-spine
      lateral radiographs were randomly selected from the radiographic database. To
      evaluate inter- and intraobserver variability between observers and method,
      skilled (2 years of experience) and unskilled (1 week of experience) observers
      measured SVA and pelvic parameters 3 times with a 7-day interval between each
      time using both computerized and manual measurement methods. The reliability was
      measured using the intraclass correlation coefficient. RESULTS: The computerized
      method showed better congruity than the manual method in both skilled and
      unskilled observers (p < 0.05), and the intraclass correlation coefficients were
      > 0.9. The skilled observer showed better agreement than the unskilled observer
      with both computerized and manual methods, and this difference was prominent in
      measuring pelvic parameters (p < 0.05). The computerized method required less
      time than the manual method, especially for the unskilled observer (p < 0.05).
      CONCLUSIONS: A computerized measurement of pelvic parameters may be a more
      reliable and efficacious approach than manual measurements. This benefit is more
      prominent in the unskilled observer, and adding this simple function to an image
      viewer may be recommended in future studies.

PMID- 22136392
TI  - Spinal cord bypass surgery with intercostal and spinal accessory nerves: an
      anatomical feasibility study in human cadavers.
AB  - OBJECT: Despite extensive study, no meaningful progress has been made in
      encouraging healing and recovery across the site of spinal cord injury (SCI) in
      humans. Spinal cord bypass surgery is an unconventional strategy in which intact
      peripheral nerves rostral to the level of injury are transferred into the spinal
      cord below the injury. This report details the feasibility of using spinal
      accessory nerves to bypass cervical SCI and intercostal nerves to bypass
      thoracolumbar SCI in human cadavers. METHODS: Twenty-three human cadavers
      underwent cervical and/or lumbar laminectomy and dural opening to expose the
      cervical cord and/or conus medullaris. Spinal accessory nerves were harvested
      from the Erb point to the origin of the nerve's first major branch into the
      trapezius. Intercostal nerves from the T6-12 levels were dissected from the
      lateral border of paraspinal muscles to the posterior axillary line. The distal
      ends of dissected nerves were then transferred medially and sequentially inserted
      4 mm deep into the ipsilateral cervical cord (spinal accessory nerve) or conus
      medullaris (intercostals). The length of each transferred nerve was measured, and
      representative distal and proximal cross-sections were preserved for axonal
      counting. RESULTS: Spinal accessory nerves were consistently of sufficient length
      to be transferred to caudal cervical spinal cord levels (C4-8). Similarly,
      intercostal nerves (from T-7 to T-12) were of sufficient length to be transferred
      in a tension-free manner to the conus medullaris. Spinal accessory data revealed
      an average harvested nerve length of 15.85 cm with the average length needed to
      reach C4-8 of 4.7, 5.9, 6.5, 7.1, and 7.8 cm. The average length of available
      intercostal nerve from each thoracic level compared with the average length
      required to reach the conus medullaris in a tension-free manner was determined to
      be as follows (available, required in cm): T-7 (18.0, 14.5), T-8 (18.7, 11.7), T
      9 (18.8, 9.0), T-10 (19.6, 7.0), T-11 (18.8, 4.6), and T-12 (15.8, 1.5). The
      number of myelinated axons present on cross-sectional analysis predictably
      decreased along both spinal accessory and intercostal nerves as they coursed
      distally. CONCLUSIONS: Both spinal accessory and intercostal nerves, accessible
      from a posterior approach in the prone position, can be successfully harvested
      and transferred to their respective targets in the cervical spinal cord and conus
      medullaris. As expected, the number of axons available to grow into the spinal
      cord diminishes distally along each nerve. To maximize axon "bandwidth" in nerve
      bypass procedures, the most proximal section of the nerve that can be transferred
      in a tension-free manner to a spinal level caudal to the level of injury should
      be implanted. This study supports the feasibility of SAN and intercostal nerve
      transfer as a means of treating SCI and may assist in the preoperative selection
      of candidates for future human clinical trials of cervical and thoracolumbar SCI
      bypass surgery.

PMID- 22136393
TI  - Screening of marine extracts for schistosomicidal activity in vitro. Isolation of
      the triterpene glycosides echinosides A and B with potential activity from the
      Sea Cucumbers Actinopyga echinites and Holothuria polii.
AB  - CONTEXT: Praziquantel (PZQ) is the drug available for the treatment of
      schistosomiasis. The reported reduced cure rates, the failure of treatment after
      PZQ administration in patients and the existence of resistant parasite strains,
      reinforce the need to rapidly discover new effective molecules against
      Schistosoma parasite. OBJECTIVE: To screen the methanol extracts of 79 marine
      organisms for their schistosomicidal activities against Schistosoma mansoni adult
      worms in vitro and perform bio-assay directed chromatography for the most active
      extracts to isolate the active compounds. MATERIALS AND METHODS: Screening of the
      marine organisms and bio-assay directed chromatography of the most active
      extracts together with identification of the active isolates using 1D and 2D NMR
      analysis, were investigated. RESULTS: RESULTS indicated that the isolates
      echinosides A and B from the sea cucumbers Actinopyga echinites Jaeger and
      Holothuria polii Delle Chiaie (Holothuriidae) were highly active. Their LC(50)
      values were equal to 0.19 MUg/ml and 0.27 MUg/ml, respectively. Detailed (1)HNMR
      data for echinosides A and B are reported here for the first time. DISCUSSION AND
      CONCLUSION: These findings demonstrate that the isolated echinosides possess
      potential in vitro schistosomicidal activity against S. mansoni adult worms.
      Therefore, echinosides are promising as lead compounds for the development of new
      schistosomicidal agents.

PMID- 22136394
TI  - Incomplete tracheal intussusception in a dog.
AB  - An 18-year-old male miniature poodle had a chronic nonproductive cough. On
      radiographic examination, an opacification resembling a foreign body was noticed
      within the trachea at the level of the sixth cervical vertebra. When the trachea
      was examined endoscopically, a circumferential flap-like lesion was found. To
      differentiate the invagination from an annular mass, thoracic computed tomography
      (CT) of the trachea was performed. There was cranial displacement and
      invagination of a tracheal segment creating the flap-like lesion. Tracheal
      intussusception should be considered as a cause of an annular tracheal mass.

PMID- 22136395
TI  - Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection.
AB  - BACKGROUND: Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a
      negative regulator of T cell-mediated immune response. Molecular changes
      associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and
      control lymphocyte proliferation. AIMS: To evaluate the frequency of CTLA-4 gene
      polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate
      to clinical and histological findings. METHODS: We evaluated 112 HCV-infected
      subjects prospectively selected and 183 healthy controls. Clinical and liver
      histological data were analysed. -318C > T, A49G and CT60 CTLA-4 single
      nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism
      by DNA fragment analysis by capillary electrophoresis in automatic sequencer.
      RESULTS: Eight AT repetitions in 3'UTR region were more frequent in HCV-infected
      subjects. We found a positive association of -318C and + 49G with HCV genotype 3
      (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association
      of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38
      respectively). Allele + 49G was also associated to aminotransferases quotients >
      3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated
      with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively
      associated to severe necroinflammatory activity scores in liver biopsies (P =
      0.045, OR 4.62). CONCLUSION: CTLA-4 gene polymorphisms were associated to HCV
      infection. Eight AT repetitions were more prevalent in HCV-infected subjects. 
      318C and + 49G alleles were associated to genotypes 1 and 3 infections and
      increased number of AT repetitions in 3'UTR region favoured severe
      necroinflammatory activity scores in liver biopsies.

PMID- 22136396
TI  - Homogamy and imprinting-like effect on mate choice preference for body height in
      the current Japanese population.
AB  - BACKGROUND: Homogamy for body height has been repeatedly documented in Western
      societies. Nevertheless, the underlying mechanism is unclear and the reasons for
      its apparent absence in non-Western societies remain unexplained. AIM: This study
      investigates spousal correlation and mate preference for height in the Japanese
      population. SUBJECTS AND METHODS: This study analyses self-reported data on the
      height of individuals, their parents and their ideal marriage partners, collected
      by a series of questionnaires on university students. RESULTS: In contrast to a
      previous study, this study found a significant positive correlation between the
      heights of Japanese spouses, after controlling for age. It also found a positive
      correlation between the heights of subjects and of their ideal partners,
      suggesting that an individual's self-referent preference may contribute to the
      observed homogamy for height. However, a subject's preference is also influenced
      by the height of his/her opposite-sex--but not same-sex--parent, where this
      effect is more prominent in male subjects. CONCLUSION: This study shows that
      homogamy for body height is present in the current Japanese population and that
      it may in part result from an individual's preference. It also indicates a
      possible role of a sexual imprinting-like mechanism in human mate choice.

PMID- 22136397
TI  - Comparison of surgical outcomes in patients with colorectal liver metastases
      versus non-colorectal liver metastases: A Chinese experience.
AB  - AIM:   To compare the surgical treatment outcomes between patients with
      colorectal liver metastases (CLM) and non-colorectal liver metastases (NCLM).
      METHODS:   The study population consisted of 132 patients undergoing hepatectomy
      at Tianjin Medical University Cancer Hospital between January 1996 and December
      2008. Survival analyses were used to assess the differences in prognosis and
      survival between groups. RESULTS:   The primary tumor site was colorectal in 60
      (45.5%), breast in 16 (12.1%), lung in 14 (10.6%), non-colorectal
      gastrointestinal in 12 (9.1%), genitourinary in 10 (7.6%), pancreatobiliary tumor
      (n = 8, 6.1%) and others in 12 (9.1%). A curative liver resection was performed
      in all patients by pathological findings. After a median follow-up of 32 months,
      the overall 3- and 5-year survival rate was 44.7 and 29.5% in all patients,
      respectively. The 3- and 5-year survival rates were 53.3 and 36.7% for liver
      metastases from colorectal tumors, 62.5 and 43.8% from breast, 60.0 and 40.0%
      from genitourinary neoplasm, 41.7 and 25.0% from non-colorectal gastrointestinal
      cancer, 28.5 and 15.0% from lung, 12.5 and 0% from pancreatobiliary malignancies,
      and 41.7 and 8.3% from other sites, respectively. CONCLUSIONS:   Hepatic
      resection is an effective and safe treatment for liver metastases mainly
      depending on primary tumor sites. Hepatic metastases from non-colorectal
      gastrointestinal cancer, pulmonary and pancreatobiliary malignancies have the
      worst prognosis; those from breast and genitourinary neoplasm show the best
      prognosis.

PMID- 22136398
TI  - Structural role of counterions adsorbed on self-assembled peptide nanotubes.
AB  - Among noncovalent forces, electrostatic ones are the strongest and possess a
      rather long-range action. For these reasons, charges and counterions play a
      prominent role in self-assembly processes in water and therefore in many
      biological systems. However, the complexity of the biological media often hinders
      a detailed understanding of all the electrostatic-related events. In this
      context, we have studied the role of charges and counterions in the self-assembly
      of lanreotide, a cationic octapeptide. This peptide spontaneously forms
      monodisperse nanotubes (NTs) above a critical concentration when solubilized in
      pure water. Free from any screening buffer, we assessed the interactions between
      the different peptide oligomers and counterions in solutions, above and below the
      critical assembly concentration. Our results provide explanations for the
      selection of a dimeric building block instead of a monomeric one. Indeed, the
      apparent charge of the dimers is lower than that of the monomers because of
      strong chemisorption. This phenomenon has two consequences: (i) the dimer-dimer
      interaction is less repulsive than the monomer-monomer one and (ii) the lowered
      charge of the dimeric building block weakens the electrostatic repulsion from the
      positively charged NT walls. Moreover, additional counterion condensation
      (physisorption) occurs on the NT wall. We furthermore show that the counterions
      interacting with the NTs play a structural role as they tune the NTs diameter. We
      demonstrate by a simple model that counterions adsorption sites located on the
      inner face of the NT walls are responsible for this size control.

PMID- 22136399
TI  - Reduced calcium/calmodulin-dependent protein kinase II activity in the
      hippocampus is associated with impaired cognitive function in MPTP-treated mice.
AB  - Parkinson's disease (PD) patients frequently reveal deficit in cognitive
      functions during the early stage in PD. The dopaminergic neurotoxin, MPTP-induced
      neurodegeneration causes an injury of the basal ganglia and is associated with PD
      like behaviors. In this study, we demonstrated that deficits in cognitive
      functions in MPTP-treated mice were associated with reduced calcium/calmodulin
      dependent protein kinase II (CaMKII) autophosphorylation and impaired long-term
      potentiation (LTP) induction in the hippocampal CA1 region. Mice were injected
      once a day for 5days with MPTP (25mg/kg i.p.). The impaired motor coordination
      was observed 1 or 2week after MPTP treatment as assessed by rota-rod and beam
      walking tasks. In immunoblotting analyses, the levels of tyrosine hydroxylase
      protein and CaMKII autophosphorylation in the striatum were significantly
      decreased 1week after MPTP treatment. By contrast, deficits of cognitive
      functions were observed 3-4weeks after MPTP treatment as assessed by novel object
      recognition and passive avoidance tasks but not Y-maze task. Impaired LTP in the
      hippocampal CA1 region was also observed in MPTP-treated mice. Concomitant with
      impaired LTP induction, CaMKII autophosphorylation was significantly decreased
      3weeks after MPTP treatment in the hippocampal CA1 region. Finally, the reduced
      CaMKII autophosphorylation was closely associated with reduced AMPA-type
      glutamate receptor subunit 1 (GluR1; Ser-831) phosphorylation in the hippocampal
      CA1 region of MPTP-treated mice. Taken together, decreased CaMKII activity with
      concomitant impaired LTP induction in the hippocampus likely account for the
      learning disability observed in MPTP-treated mice.

PMID- 22136401
TI  - Enteral nutrition: better navigation, yet unknown destination?
AB  - The nutrition dose truly absorbed by a patient is crucial information in the
      management or the investigation of nutrition during critical illness. In the
      present issue of Critical Care, assessment of nutritional losses in stools was
      studied. These losses together with enteral nutrition lost in gastric fluids and
      enteral nutrition prescribed but never infused make up the difference between the
      dose supposedly given to a patient and the amount effectively taken up.
      Additionally, the optimal dosing and timing of nutrition during critical illness
      are still debated. When enteral nutrition is insufficient, the options are
      limited.

PMID- 22136402
TI  - First-order reversal curve probing of spatially resolved polarization switching
      dynamics in ferroelectric nanocapacitors.
AB  - Spatially resolved polarization switching in ferroelectric nanocapacitors was
      studied on the sub-25 nm scale using the first-order reversal curve (FORC)
      method. The chosen capacitor geometry allows both high-veracity observation of
      the domain structure and mapping of polarization switching in a uniform field,
      synergistically combining microstructural observations and probing of uniform
      field polarization responses as relevant to device operation. A classical
      Kolmogorov-Avrami-Ishibashi model has been adapted to the voltage domain, and the
      individual switching dynamics of the FORC response curves are well approximated
      by the adapted model. The comparison with microstructures suggests a strong
      spatial variability of the switching dynamics inside the nanocapacitors.

PMID- 22136403
TI  - Inferring extinction of mammals from sighting records, threats, and biological
      traits.
AB  - For species with five or more sightings, quantitative techniques exist to test
      whether a species is extinct on the basis of distribution of sightings. However,
      70% of purportedly extinct mammals are known from fewer than five sightings, and
      such models do not include some important indicators of the likelihood of
      extinction such as threats, biological traits, search effort, and demography.
      Previously, we developed a quantitative method that we based on species' traits
      in which we used Cox proportional hazards regression to calculate the probability
      of rediscovery of species regarded as extinct. Here, we used two versions of the
      Cox regression model to determine the probability of extinction in purportedly
      extinct mammals and compared the results of these two models with those of
      stationary Poisson, nonparametric, and Weibull sighting-distribution models. For
      mammals with five or more sightings, the stationary Poisson model categorized all
      but two critically endangered (flagged as possibly extinct) species in our data
      set as extinct, and results with this model were consistent with current
      categories of the International Union for the Conservation of Nature. The scores
      of probability of rediscovery for individual species in one version of our Cox
      regression model were correlated with scores assigned by the stationary Poisson
      model. Thus, we used this Cox regression model to determine the probability of
      extinction of mammals with sparse records. On the basis of the Cox regression
      model, the most likely mammals to be rediscovered were the Montane monkey-faced
      bat (Pteralopex pulchra), Armenian myotis (Myotis hajastanicus), Alcorn's pocket
      gopher (Pappogeomys alcorni), and Wimmer's shrew (Crocidura wimmeri). The Cox
      model categorized two species that have recently disappeared as extinct: the
      baiji (Lipotes vexillifer) and the Christmas Island pipistrelle (Pipistrellus
      murrayi). Our new method can be used to test whether species with few records or
      recent last-sighting dates are likely to be extinct.

PMID- 22136404
TI  - Fragment-based discovery of bromodomain inhibitors part 1: inhibitor binding
      modes and implications for lead discovery.
AB  - Bromodomain-containing proteins are key epigenetic regulators of gene
      transcription and readers of the histone code. However, the therapeutic benefits
      of modulating this target class are largely unexplored due to the lack of
      suitable chemical probes. This article describes the generation of lead molecules
      for the BET bromodomains through screening a fragment set chosen using structural
      insights and computational approaches. Analysis of 40 BRD2/fragment X-ray
      complexes highlights both shared and disparate interaction features that may be
      exploited for affinity and selectivity. Six representative crystal structures are
      then exemplified in detail. Two of the fragments are completely new bromodomain
      chemotypes, and three have never before been crystallized in a bromodomain, so
      our results significantly extend the limited public knowledge-base of
      crystallographic small molecule/bromodomain interactions. Certain fragments
      (including paracetamol) bind in a consistent mode to different bromodomains such
      as CREBBP, suggesting their potential to act as generic bromodomain templates. An
      important implication is that the bromodomains are not only a phylogenetic family
      but also a system in which chemical and structural knowledge of one bromodomain
      gives insights transferrable to others.

PMID- 22136405
TI  - Neuropsychological and neurophysiological effects of strengthening exercise for
      early dementia: a pilot study.
AB  - Research demonstrates a positive effect of aerobic exercise on cognitive
      functioning in older adults. Unfortunately, aerobic exercise is often
      contraindicated for older adults due to cardiovascular and functional
      limitations. Low-intensity strengthening exercise may offer a practical
      alternative, but the neuropsychological benefits and potential neurophysiological
      mechanisms are less well understood. The current study evaluated the effects of a
      10-week strengthening exercise intervention on cognitive functioning and EEG in a
      sample of 13 older adults with early dementia, and 9 normative controls. Results
      revealed beneficial effects of strengthening exercise on verbal memory coupled
      with frontal beta and delta power asymmetries and N200 amplitude asymmetry.
      Results point to increased cognitive efficiency following 10 weeks of
      strengthening exercise. The findings suggest it is feasible to conduct a
      strengthening intervention with early dementia patients, and to gather
      neuropsychological and neurophysiological data to evaluate outcomes.
      Strengthening exercise may serve as a useful alternative to aerobic exercise.

PMID- 22136406
TI  - Association between antibodies to Coxiella burnetii in bulk tank milk and
      perinatal mortality of Danish dairy calves.
AB  - BACKGROUND: Coxiella burnetii is a well-known cause of placentitis and subsequent
      abortion in ruminants, but there are no reports on the relationship with
      perinatal mortality. The study was performed to determine the influence of level
      and change of bulk tank milk (BTM) antibodies to C. burnetii on two outcomes
      associated with parturition in cattle: a) stillbirth; and b) stillbirth and
      neonatal mortality combined (perinatal death). METHODS: Twenty-four Danish dairy
      herds were tested repeatedly for antibodies to C. burnetii in BTM using a
      commercial ELISA. Samples were collected monthly from July 2008 to July 2009.
      Information on the 2,362 calvings occurring in the study period was obtained from
      the Danish Cattle Database. Two multilevel logistic regression models were
      created for the two outcomes stillbirth and perinatal mortality. One model
      included the level of BTM antibodies in a specified period before or after the
      outcome had occurred. The other model included the change in antibodies over
      time. These predictors were included both at herd and animal level. Furthermore,
      all models included parity and breed. RESULTS: The individual monthly BTM
      antibody levels were highly correlated within herds. Consequently, changes in BTM
      antibody levels were not found to be associated with neither risk of stillbirth
      nor the risk of perinatal mortality. However, the risk of stillborn calves and
      perinatal death was higher with high level of BTM antibodies 8 to 9 months after
      the incident, but not outside this period. CONCLUSION: We conclude that the level
      of antibodies to C. burnetii in BTM may be associated with perinatal mortality,
      but the association was not persistent and should be investigated further.

PMID- 22136407
TI  - Analgesic concentrations of oxycodone--a prospective clinical PK/PD study in
      patients with laparoscopic cholecystectomy.
AB  - The analgesic concentrations of oxycodone in acute post-operative pain management
      have not been established. Here, we have evaluated the minimum effective
      concentration (MEC) and the minimum effective analgesic concentration (MEAC) of
      oxycodone in pain after laparoscopic cholecystectomy (LCC) in 23 adult patients.
      The patients were provided with 0.1 mg/kg of oxycodone i.v. 10-15 min. before the
      end of surgery. After surgery, when the wound pain at rest was >=3/10 and/or
      >=5/10 during wound compression, a first blood sample was obtained (MEC). A
      second blood sample was obtained after titration with 2 mg i.v. of oxycodone to
      wound pain <3/10 at rest and <5/10 during wound compression (MEAC). A third blood
      sample was obtained at the recurrence of the wound pain (the second MEC), and the
      final blood sample when pain relief was obtained a second time (the second MEAC).
      At the first onset of pain (MEC), mean P-oxycodone was 21 ng/mL (95% CI 13-29
      ng/mL). At the first pain relief (MEAC), P-oxycodone was 55 ng/mL (19-91 ng/mL).
      The second MEC was 34 ng/mL (11-57 ng/mL), and the second MEAC was 47 ng/mL (14
      80 ng/mL). In conclusion, the estimated MEC, 20-35 ng/mL, and MEAC, 45-50 ng/mL,
      values of P-oxycodone in patients after LLC were significantly higher than those
      proposed previously. Early pain after LCC appeared to be a feasible method to
      estimate the analgesic efficacy of oxycodone in acute pain management.

PMID- 22136408
TI  - Simulation of haemodynamic flow in head and neck cancer chemotherapy.
AB  - BACKGROUND: In recent years, intra arterial chemotherapy has become an important
      component in head and neck cancer treatment. However, therapy success can vary
      significantly and consistent treatment guidelines are missing. The purpose of
      this study was to create a computer simulation of the chemical agent injection in
      the head and neck arteries to investigate the distribution and concentration of
      the chemical. METHODS: Realistic three dimensional patient specific geometry was
      created from image scan data. Pulsatile blood flow, turbulence, the chemical
      agent injection via a catheter, and the mixture between blood and the chemical
      were then simulated through the arterial network by computational fluid dynamics
      software. RESULTS: The results show a consistent chemical distribution throughout
      all the arteries and this is ineffective. In addition, due to high wall shear
      stress and turbulence at the inner bifurcation wall, serious complications during
      the treatment could occur, for instance haemolysis or thrombosis. CONCLUSIONS:
      The modelled catheter position is insufficient to provide a high chemical agent
      concentration in the desired tumour feeding artery, which is vital for therapy
      success.

PMID- 22136409
TI  - Mass spectrometry-based analysis of proteomic changes in the root tips of flooded
      soybean seedlings.
AB  - Flooding injury is a major problem in soybean cultivation. A proteomics approach
      was used to clarify the occurrence of changes in protein expression level and
      phosphorylation in soybeans under flooding stress. Two-day-old seedlings were
      flooded for 1 day, proteins were extracted from root tips of the seedlings and
      digested with trypsin, and their expression levels and phosphorylation states
      were compared to those of untreated controls using mass spectrometry-based
      proteomics techniques. Phosphoproteins were enriched using a phosphoprotein
      purification column prior to digestion and mass spectrometry. The expression of
      proteins involved in energy production increased as a result of flooding, while
      expression of proteins involved in protein folding and cell structure maintenance
      decreased. Flooding induced changes of phosphorylation status of proteins
      involved in energy generation, protein synthesis and cell structure maintenance.
      The response to flooding stress may be regulated by both modulation of protein
      expression and phosphorylation state. Energy-demanding and production-related
      metabolic pathways may be particularly subject to regulation by changes in
      protein phosphorylation during flooding.

PMID- 22136410
TI  - Borderline nuclear change, high-grade dyskaryosis not excluded: current concepts
      and impact on clinical practice.
AB  - OBJECTIVE: Borderline nuclear change, high-grade dyskaryosis not excluded (B/HG)
      is a subcategory of the borderline category recommended by the British Society
      for Clinical Cytology as warranting direct referral to colposcopy. This
      subcategory is equivalent to the Bethesda category of atypical squamous cells,
      cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of
      this study was to determine the validity and accuracy of using B/HG to identify
      potential cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+).
      METHODS: Data were collected from the hospital pathology database for borderline,
      B/HG and high-grade cytology (moderate dyskaryosis and above), and their
      respective histological and colposcopic outcomes. SPSS was used for data
      analysis. RESULTS: Of the 84,799 total cytology samples screened between July
      2006 and December 2009, 5225 (6.1%) were reported as borderline, 309 (0.4%) as
      B/HG and 1222 (1.4%) as high-grade cytology. Thus, B/HG comprised 5.9% of the
      overall borderline category, in keeping with national guidelines (<10%). CIN2+
      was confirmed in 86.6% of high-grade, 40.8% of B/HG and 3.0% of borderline
      cytology. Of 309 women reported with B/HG cytology, 239 had colposcopy.
      Colposcopic appearances showed a positive predictive value (PPV) of 71.8% for
      detecting CIN2+ and a negative predictive value of 60.7%. CONCLUSIONS: The B/HG
      category was associated with a significantly higher incidence of CIN2+ compared
      with borderline cytology as a whole. This refining performance justifies its
      existence. Colposcopic appearances had a high PPV for detecting CIN2+. Therefore,
      colposcopy is recommended in patients with B/HG cytology and treatment should be
      offered if high-grade colposcopic changes are seen.

PMID- 22136412
TI  - Chloride-based CVD growth of silicon carbide for electronic applications.

PMID- 22136411
TI  - SPARC modulates expression of extracellular matrix genes in human trabecular
      meshwork cells.
AB  - PURPOSE: To investigate the effects of secreted protein acidic and rich in
      cysteine (SPARC) on the expression of components of the extracellular matrix
      (ECM) in cultured human trabecular meshwork (TM) cells. METHODS: Cultured human
      trabecular cells were transfected with small interfering RNAs (siRNAs) specific
      for the human SPARC gene. Protein and mRNA expressions of fibronectin (FN) and
      the alpha1chains of collagen I and collagen III were quantified. RESULTS: After
      silencing of the SPARC gene by transfection of cells with SPARC siRNA, the
      expression of COL1A1 and COL3A1 mRNAs and proteins was significantly enhanced, as
      compared to that in the control group (all, p < 0.001). In contrast, SPARC siRNA
      significantly reduced the expression of FN and SPARC mRNAs and FN protein, as
      compared to that in the control group (all, p < 0.001.). CONCLUSIONS: SPARC
      modulates the expression of several ECM genes in cultured human TM cells.

PMID- 22136413
TI  - Reversal of haloperidol-induced orofacial dyskinesia by Murraya koenigii leaves
      in experimental animals.
AB  - CONTEXT: Orofacial dyskinesia (OD) is a late complication of prolonged
      neuroleptic treatment characterized by involuntary movements of the oral region.
      Chronic treatment with neuroleptics leads to development of vacuous chewing
      movements (VCMs). VCMs in rats are widely accepted as an animal model of OD.
      OBJECTIVE: To study the effect of Murraya koenigii L. (Rutaceae) leaves on
      haloperidol-induced OD. MATERIALS AND METHODS: Effect of alcohol extract of M.
      koenigii leaves (EEMK) and its alkaloid fraction (AMK) on body weight, locomotor
      activity, behavioral parameters, such as VCMs, tongue protrusions (TPs),
      orofacial bursts (OBs), and biochemical parameters such as antioxidant defense
      enzymes levels [superoxide dismutase (SOD) and catalase (CAT)], glutathione (GSH)
      levels, and lipid peroxidation (LPO) in the forebrain region was studied in
      haloperidol-treated rats. RESULTS: Rats chronically treated with haloperidol (1
      mg/kg, i.p., 21 days) significantly decreased locomotion and developed VCMs, OBs,
      and TPs. Biochemical analysis reveals that chronic haloperidol-treated rats also
      showed decreased levels of SOD and CAT. Chronic haloperidol treatment
      significantly induced LPO and decreased the forebrain GSH levels in the rats. Co
      administration of EEMK (100 and 300 mg/kg, p.o.) and AMK (30 and 100 mg/kg, p.o.)
      along with haloperidol significantly reversed the effect on locomotion. EEMK and
      AMK significantly reversed the haloperidol-induced decrease in forebrain SOD and
      CAT levels in rats and significantly reduced the LPO and restored the decreased
      GSH levels by chronic haloperidol treatment. CONCLUSION: The study concludes that
      M. koenigii could be screened as a potential drug for the prevention or treatment
      of neuroleptic-induced OD.

PMID- 22136415
TI  - Knowledge, attitudes, practices, and barriers reported by patients receiving
      diabetes and hypertension primary health care in Barbados: a focus group study.
AB  - BACKGROUND: Deficiencies in the quality of diabetes and hypertension primary care
      and outcomes have been documented in Barbados. This study aimed to explore the
      knowledge, attitudes and practices, and the barriers faced by people with
      diabetes and hypertension in Barbados that might contribute to these
      deficiencies. METHODS: Five structured focus groups were conducted for randomly
      selected people with diabetes and hypertension. RESULTS: Twenty-one patients (5
      diabetic, 5 hypertensive, and 11 with both diseases) with a mean age of 59 years
      attended 5 focus group sessions.Patient factors that affected care included the
      difficulty in maintaining behaviour change. Practitioner factors included not
      considering the "whole person" and patient expectations, and not showing enough
      respect for patients. Health care system factors revolved around the amount of
      time spent accessing care because of long waiting times in public sector clinics
      and pharmacies. Society related barriers included the high cost and limited
      availability of appropriate food, the availability of exercise facilities, stigma
      of disease and difficulty taking time off work.Attendees were not familiar with
      guidelines for diabetes and hypertension management, but welcomed a patient
      version detailing a place to record results, the frequency of tests, and blood
      pressure and blood glucose targets. Appropriate education from practitioners
      during consultations, while waiting in clinic, through support and education
      groups, and for the general public through the schools, mass media and billboards
      were recommended. CONCLUSIONS: Primary care providers should take a more patient
      centred approach to the care of those with diabetes and hypertension. The care
      system should provide better service by reducing waiting times. Patient self
      management could be encouraged by a patient version of care guidelines and
      greater educational efforts.

PMID- 22136416
TI  - Hepatic veno-occlusive disease after taking Gynura Rhizome: The value of
      multidetector computed tomography in diagnosing the disease and evaluating the
      clinical therapeutic effect.
AB  - AIM:   We conducted this study to evaluate the role of multidetector computed
      tomography (MDCT) in diagnosing and differential diagnosis hepatic veno-occlusive
      disease (HVOD), and as well as assessing the clinical therapeutic effects.
      METHODS:   From 2007 to 2010, 10 inpatients with weight increasing, liver pains,
      ascites, jaundice and history of taking gynura rhizome before hospitalization
      were scanned with a 64-MDCT. The data were reconstructed every 0.625 mm and
      reviewed using multiplanar reconstruction (MPR) and liver CT angiography (CTA) on
      a GE AW4.2 workstation. Patients were re-scanned with MDCT after medication so
      that the clinical therapeutic effect could be evaluated before the patients
      discharging from hospital. RESULTS:   In 10 HVOD patients, the diagnoses of MDCT
      were coincident with clinical results. All patients had ascites and pleural
      fluid, hepatomegaly except the caudate lobe in MDCT. Failure to view hepatic
      veins in hepatic 3 phase scans, but portal veins and inferior vena cava were
      unobstructed. In portal-phase, hepatic enhancements were non-uniform. Three
      patients were incorrectly diagnosed before hospital admission. All patients
      improved significantly after hepato-protection and supporting therapy. No
      ascites, hydrothorax, hepatomegaly and obstruction of hepatic veins were observed
      by MDCT before patients were discharged from hospital. CONCLUSION:  
      Multidetector computed tomography combined with MPR and liver CTA images are
      helpful in the diagnosis and differential diagnosis of HVOD and in the evaluation
      of clinical therapeutic effects.

PMID- 22136417
TI  - Recognition-mediated light-up of thiazole orange with cucurbit[8]uril: exchange
      and release by chemical stimuli.
AB  - This article reports a convenient supramolecular strategy to construct
      fluorescent photoswitchable molecular assemblies between a macrocyclic host,
      cucurbit[8]uril (CB8), and a fluorogenic dye, thiazole orange (TO). The
      interaction mechanism and the stable stoichiometric host-guest arrangements have
      been claimed on the basis of the optical absorption, steady-state and time
      resolved fluorescence lifetime and anisotropy measurements, and also the geometry
      optimization studies. The CB8 recognized TO in its 2:2 stoichiometry exhibited
      spectacular fluorescence enhancement of the order of 1700 fold, which is the
      largest directly determined value so far reported for a dye in an organic
      macrocyclic system. This prospective 2CB8:2TO assembly responded to selected
      chemical stimuli such as metal ions, adamantylamine, and tryptophan, providing
      different dissociation mechanisms and demonstrating a controlled exchange and
      release action desired with such noncovalently linked assemblies. Positively,
      considering the aqueous solubility and biocompatibility of the host-guest
      constituents, this methodology can evolve into a general approach to deliver and
      operate intracellularly functional molecular components under
      chemical/thermal/optical trigger control, especially for therapeutic
      applications.

PMID- 22136418
TI  - Influenza virus: a single noninfectious interferon induction-suppressing particle
      blocks expression of interferon-inducing particles.
AB  - The interferon (IFN)-inducing capacity of influenza virus plays a significant
      role in the efficacy of candidate live attenuated influenza vaccines (LAIVs). IFN
      is induced by a subpopulation of noninfectious biologically active particles
      (niBAPs) that can be defined and quantified as IFN-inducing particles (IFPs).
      When chicken embryonic cells were infected with increasing multiplicities of IFP
      (m(ifp)), the amount of IFN produced was that expected from a Poisson
      distribution of cells infected with >=1 IFP. Problematically, some isolates of
      influenza virus induced less IFN than expected at higher m(ifp). We postulated
      that these stocks contained another subpopulation of niBAP, IFN induction
      suppressing particles (ISPs). A single ISP was assumed capable of preventing IFN
      production completely in cells coinfected with IFP. Virus stocks were
      reconstructed to contain a wide range of ratios of IFP:ISP and used to generate
      IFN-induction dose-response curves. The deviation of the observed yields of IFN
      from those expected if the virus stock consisted only of IFP fits well the
      results expected from a formulation of the Poisson distribution that provides the
      fraction of IFP-infected cells expected to become coinfected with ISP, and hence
      not yield IFN, as the ratio IFP:ISP decreases. The ideal LAIV might be thought to
      contain little or no ISP so as to maximize IFN production; however, the most
      effective LAIV appear to regulate the production of IFN. Thus, it is possible
      that an optimal ratio of IFP:ISP may exist to produce more effective LAIV, an
      event that may sometimes occur in nature, or be reconstructed.

PMID- 22136419
TI  - Gender roles and substance use among Mexican American adolescents: a relationship
      moderated by acculturation?
AB  - This research assesses the effects of adaptive/ maladaptive gender roles and
      acculturation in predicting substance use in a 2007 sample of 1466 Mexican
      American seventh-grade adolescents from Phoenix, Arizona, U.S.A. Multiple
      regression analyses found significant effects for both adaptive and maladaptive
      gender roles, as well as several gender-specific interactions between gender
      roles and linguistic acculturation that predicted substance use. Limitations of
      the research are noted, as well as implications for understanding the impact of
      acculturation on how gender roles differentially affect substance use in Mexican
      American boys versus girls.

PMID- 22136420
TI  - Left ventricular morphology and function in diabetic and nondiabetic hemodialyzed
      patients.
AB  - Morbidity in end-stage renal disease (ESRD) diabetic patients is worse than in
      patients without diabetes mellitus (DM). This study aims to compare clinical,
      laboratory, and echocardiographic features between the ESRD patients with and
      without DM. Fifty-eight ESRD patients on dialysis were prospectively divided into
      two groups according to the presence of DM. Demographic, clinical, laboratory,
      and echocardiographic features (ejection fraction and wall motion score index)
      were compared between the two groups. Overall, 20 out of 58 patients (37.8%) with
      ESRD had DM. There were no significant differences between the patients with DM
      and those without DM when it comes to age (60.6 +/- 10.6 vs. 59.0 +/- 10.6 years,
      P = 0.665), ejection fraction (52.6% +/- 12.8% vs. 54.2% +/- 12.8%, P = 0.59),
      and wall motion score index (1.21 +/- 0.3 vs.1.15 +/- 0.3, P = 0.37). In
      multivariant analysis of the interventricular septum, posterior wall thickness
      and left atrium size correlated positively with DM. There was also no statistical
      difference in myocardial perfusion disturbances on real-time contrast
      echocardiography between the groups with and without DM (12 (60%) patients vs. 14
      patients (36.8%), P = 0.079). Among diabetics 77.8% had significant
      atherosclerotic changes, while in the group without DM, only 38.1%, P = 0.01.
      From the laboratory parameters ferritin and high-sensitivity C-reactive protein
      levels were significantly higher in the group with DM, P = 0.014 and P = 0.026,
      respectively. Patients with ESRD and DM have significantly bigger left atrial
      size, thicker left ventricular walls, and higher serum ferritin and high
      sensitivity C-reactive protein levels than the patients without DM. The
      aforementioned features may be possible risk factors for the development of
      adverse cardiac events in patients on hemodialysis.

PMID- 22136421
TI  - GPx-Like activity of selenides and selenoxides: experimental evidence for the
      involvement of hydroxy perhydroxy selenane as the active species.
AB  - The reaction mechanism of the GPx-like oxidation of PhSH with H(2)O(2) catalyzed
      by selenoxides proceeds via formation of the hydroxy perhydroxy selenane, which
      is a stronger oxidizing agent than selenoxide. A hydroxy perhydroxy selenane
      intermediate was observed by electrospray ionization mass spectrometry and (77)Se
      NMR spectroscopy in reactions of selenoxide 8 with H(2)O(2).The initial velocity
      of oxidation of PhSH by H(2)O(2) with selenoxide 8 is 4 orders of magnitude
      higher than that of 8 without peroxide. Selenoxide 8 is not reduced to selenide 6
      by PhSH in the presence of H(2)O(2). While electronic substituent effects have
      minimal impact on the catalytic performance of selenoxides, chelating groups
      increase the rate of catalysis.

PMID- 22136422
TI  - Effects of probiotics on serum levels of Th1/Th2 cytokine and clinical outcomes
      in severe traumatic brain-injured patients: a prospective randomized pilot study.
AB  - INTRODUCTION: Traumatic brain injury (TBI) is associated with a profound
      immunological dysfunction manifested by a severe shift from T-helper type 1 (Th1)
      to T-helper type 2 (Th2) response. This predisposes patients to infections,
      sepsis, and adverse outcomes. Probiotic bacteria have been shown to balance the
      Th1/Th2 cytokines in allergic murine models and patients. For the present study,
      we hypothesized that the enteral administration of probiotics would adjust the
      Th1/Th2 imbalance and improve clinical outcomes in TBI patients. METHODS: We
      designed a prospective, randomized, single-blind study. Patients with severe TBI
      and Glasgow Coma Scale scores between 5 and 8 were included, resulting in 26
      patients in the control group and 26 patients in the probiotic group. All
      patients received enteral nutrition via a nasogastric tube within 24 to 48 hours
      following admission. In addition, the probiotic group received 109 bacteria of
      viable probiotics per day for 21 days. The associated serum levels of Th1/Th2
      cytokines, Acute Physiology and Chronic Health Evaluation (APACHE) II and
      Sequential Organ Failure Assessment (SOFA) scores, nosocomial infections, length
      of ICU stay, and 28-day mortality rate were studied. RESULTS: The patients
      responded to viable probiotics, and showed a significantly higher increase in
      serum IL-12p70 and IFNgamma levels while also experiencing a dramatic decrease in
      IL-4 and IL-10 concentrations. APACHE II and SOFA scores were not significantly
      affected by probiotic treatment. Patients in the probiotic group experienced a
      decreased incidence of nosocomial infections towards the end of the study.
      Shorter ICU stays were also observed among patients treated with probiotic
      therapy. However, the 28-day mortality rate was unaffected. CONCLUSIONS: The
      present study showed that daily prophylactic administration of probiotics could
      attenuate the deviated Th1/Th2 response induced by severe TBI, and could result
      in a decreased nosocomial infection rate, especially in the late period. TRIAL
      REGISTRATION: ChiCTR-TRC-10000835.

PMID- 22136423
TI  - Significance of IDH mutations varies with tumor histology, grade, and genetics in
      Japanese glioma patients.
AB  - Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found frequently in
      malignant gliomas and are likely involved in early gliomagenesis. To understand
      the prevalence of these mutations and their relationship to other genetic
      alterations and impact on prognosis for Japanese glioma patients, we analyzed 250
      glioma cases. Mutations of IDH1 and IDH2 were found in 73 (29%) and 2 (1%) cases,
      respectively. All detected mutations were heterozygous, and most mutations were
      an Arg132His (G395A) substitution. IDH mutations were frequent in
      oligodendroglial tumors (37/52, 71%) and diffuse astrocytomas (17/29, 59%), and
      were less frequent in anaplastic astrocytomas (8/29, 28%) and glioblastomas
      (13/125, 10%). The pilocytic astrocytomas and gangliogliomas did not have either
      mutation. Notably, 28 of 30 oligodendroglial tumors harboring the 1p/19q co
      deletion also had an IDH mutation, and these alterations were significantly
      correlated (P < 0.001). The association between TP53 and IDH mutation was
      significant in diffuse astrocytomas (P = 0.0018). MGMT promoter methylation was
      significantly associated with IDH mutation in grade 2 (P < 0.001) and grade 3 (P
      = 0.02) gliomas. IDH mutation and 1p/19q co-deletion were independent favorable
      prognostic factors for patients with grade 3 gliomas. For patients with grade 3
      gliomas and without 1p/19q co-deletion, IDH mutation was strongly associated with
      increased progression-free survival (P < 0.0001) and overall survival (P <
      0.0001), but no such marked correlation was observed with grade 2 gliomas or
      glioblastomas. Therefore, IDH mutation would be most useful when assessing
      prognosis of patients with grade 3 glioma with intact 1p/19q; anaplastic
      astrocytomas account for most of these grade 3 gliomas.

PMID- 22136425
TI  - Nitrogen-doped graphene/ZnSe nanocomposites: hydrothermal synthesis and their
      enhanced electrochemical and photocatalytic activities.
AB  - Nitrogen-doped graphene (GN) has great potential applications in many fields
      because doping with nitrogen can alter the electrical properties of graphene. It
      is still a challenge to develop a convenient method for synthesis of GN sheets.
      In this paper, we first report the synthesis of a nitrogen-doped graphene/ZnSe
      nanocomposite (GN-ZnSe) by a one-pot hydrothermal process at low temperature
      using graphene oxide nanosheets and [ZnSe](DETA)(0.5) nanobelts as precursors.
      ZnSe nanorods composed of ZnSe nanoparticles were found to deposit on the surface
      of the GN sheets. The results demonstrated that [ZnSe](DETA)(0.5) nanobelts were
      used not only as the source of ZnSe nanoparticles but also as the nitrogen
      source. Interestingly, it was found that the as-prepared nanocomposites exhibit
      remarkably enhanced electrochemical performance for oxygen reduction reaction and
      photocatalytic activities for the bleaching of methyl orange dye under visible
      light irradiation. This facile and catalyst-free approach for depositing ZnSe
      nanoparticles onto the graphene sheets may provide an alternative way for
      preparation of other nanocomposites based on GN sheets under mild conditions,
      which show their potential applications in wastewater treatment, fuel cells,
      energy storage, nanodevices, and so on.

PMID- 22136426
TI  - Effects of varied ionic calcium and phosphate on the proliferation, osteogenic
      differentiation and mineralization of human periodontal ligament cells in vitro.
AB  - BACKGROUND AND OBJECTIVE: A number of bone-filling materials containing calcium
      (Ca(2+) ) and phosphate (P) ions have been used in the repair of periodontal bone
      defects; however, the effects that local release of Ca(2+) and P ions has on
      biological reactions are not fully understood. In this study, we investigated the
      effects of various levels of Ca(2+) and P ions on the proliferation, osteogenic
      differentiation and mineralization of human periodontal ligament cells (hPDLCs).
      MATERIAL AND METHODS: The hPDLCs were obtained using an explant culture method.
      Defined concentrations and ratios of ionic Ca(2+) to inorganic P were added to
      standard culture and osteogenic induction media. The ability of hPDLCs to
      proliferate in these growth media was assayed using the Cell Counting Kit-8. Cell
      apoptosis was evaluated by the fluorescein isothiocyanate-annexin V/propidium
      iodide double-staining method. Osteogenic differentiation and mineralization were
      investigated by morphological observations, alkaline phosphatase activity and
      Alizarin Red S/von Kossa staining. The mRNA expression of osteogenic related
      markers was analysed using RT-PCR. RESULTS: Within the ranges of Ca(2+) and P ion
      concentrations tested, we observed that increased concentrations of Ca(2+) and P
      ions enhanced cell proliferation and formation of mineralized matrix nodules,
      whereas alkaline phosphatase activity was reduced. The RT-PCR results showed that
      elevated concentrations of Ca(2+) and P ions led to a general increase of Runx2
      mRNA expression and decreased alkaline phosphatase mRNA expression, but gave no
      clear trend on osteocalcin mRNA levels. CONCLUSION: The concentrations and ratios
      of Ca(2+) and P ions could significantly influence proliferation, differentiation
      and mineralization of hPDLCs. Within the range of concentrations tested, we found
      that the combination of 9.0 mm Ca(2+) ions and 4.5 mm P ions were the optimal
      concentrations for proliferation, differentiation and mineralization in hPDLCs.

PMID- 22136427
TI  - Magnetic resonance imaging of canine mast cell tumors.
AB  - Mast cell tumors (MCT) are the most common cutaneous tumors in dogs. Our purpose
      was to describe the magnetic resonance (MR) imaging characteristics of cutaneous
      MCT and to identify imaging characteristics that allow differentiation of
      metastatic from normal lymph nodes. Eight dogs with a total of nineMCT were
      imaged as were their presumed draining and associated contralateral lymph nodes.
      The signal intensity of tumors and lymph nodes was compared to adjacent
      musculature. On T2-W images, 7/9 MCT were hyperintense to muscle and 2/9 were
      isointense. On T1-W images, 8/9 MCT were isointense and 1/9 were mildly
      hypointense. All tumors were strongly contrast enhancing; 5/9 were homogeneous
      and 4/9 heterogeneous in their enhancement patterns. Six lymph node pairs were
      included in the evaluation (five sentinel lymph nodes with metastases, one
      without, and six contralateral lymph nodes). Metastatic lymph nodes were
      significantly larger than their contralateral lymph nodes (P = 0.039). All lymph
      nodes were isointense on T1-W images and hyperintense on T2-W images. 5/5
      metastatic and 2/7 normal lymph nodes were heterogeneously T2-hyperintense. All
      lymph nodes were moderately to strongly contrast enhancing. 4/5 metastatic and
      2/7 normal lymph nodes had heterogeneous enhancement patterns. While
      heterogeneity was more common in metastatic than in normal lymph nodes, this
      difference was not significant (P = 0.058 for T2-W images; P = 0.234 for
      postcontrast images). MR imaging may be useful in the presurgical evaluation and
      clinical staging of cutaneous MCT.

PMID- 22136428
TI  - Biology and significance of signalling pathways activated by IGF-II.
AB  - Insulin-like growth factor-II (IGF-II) affects many aspects of cellular function
      through its ability to activate several different receptors and, consequently,
      numerous intracellular signalling molecules. Thus, IGF-II is a key regulator of
      normal foetal development and growth. However, abnormalities in IGF-II function
      are associated with cardiovascular disease and cancer. Here, we review the
      cellular mechanisms by which IGF-II's physiological and pathophysiological
      actions are exerted by discussing the involvement of the type 1 and type 2 IGF
      receptors (IGF1R and IGF2R), the insulin receptor and the downstream MAP kinase,
      PI-3 kinase and G-protein-coupled signalling pathways in mediating IGF-II
      stimulated cellular proliferation, survival, differentiation and migration.

PMID- 22136429
TI  - Age benefits in everyday prospective memory: the influence of personal task
      importance, use of reminders and everyday stress.
AB  - The present diary study examined everyday prospective memory tasks in younger and
      old adults and explored the role of personal task importance, use of reminders
      and everyday stress as possible correlates of age-related prospective memory
      performance in everyday life. Results revealed an age benefit in everyday
      prospective memory tasks. In addition, task importance was identified as a
      critical moderator of age-related prospective memory performance. More frequent
      use of reminders and lower levels of stress, however, were associated with better
      prospective memory performance in general but did not contribute to age-related
      prospective memory performance. Exploring further possible correlates of
      prospective memory revealed that the strategy to reprioritize initially planned
      intentions was associated with age benefits in everyday prospective memory.
      Results suggest that the age-related benefit observed in experimenter-given tasks
      transfers to everyday prospective memory and varies in dependence of motivational
      and cognitive factors. Implications for theoretical models of prospective memory
      and aging are discussed.

PMID- 22136430
TI  - Decoupling fragmentation from habitat loss for spiders in patchy agricultural
      landscapes.
AB  - Habitat loss reduces species diversity, but the effect of habitat fragmentation
      on number of species is less clear because fragmentation generally accompanies
      loss of habitat. We compared four methods that aim to decouple the effects of
      fragmentation from the effects of habitat loss. Two methods are based on species
      area relations, one on Fisher's alpha index of diversity, and one on plots of
      cumulative number of species detected against cumulative area sampled. We used
      these methods to analyze the species diversity of spiders in 2, 3.2 * 4 km
      agricultural landscapes in Southern Judea Lowlands, Israel. Spider diversity
      increased as fragmentation increased with all four methods, probably not because
      of the additive within-patch processes, such as edge effect and heterogeneity.
      The positive relation between fragmentation and species diversity might reflect
      that most species can disperse through the fields during the wheat-growing
      season. We suggest that if a given area was designated for the conservation of
      spiders in Southern Judea Lowlands, Israel, a set of several small patches may
      maximize species diversity over time.

PMID- 22136432
TI  - History of Acta Ophthalmologica - the first 50 years.
AB  - Acta Ophthalmologica appeared as the scientific journal of the Nordic
      ophthalmological Societies in 1923. The intention was to expose the clinical and
      experimental developments among the ophthalmological communities of the four
      Nordic countries: Denmark, Finland, Norway and Sweden. The collaboration within
      the field of ophthalmology had been attempted with the publication of 'Nordisk
      ophthalmologisk Tidsskrift' in the years 1889-1892. Now, once again, the wish for
      a tighter Nordic cooperation was explored by enthusiastic ophthalmologists in all
      four countries. One person stands out as the driving force, K.K.K. Lundsgaard,
      who in spite of his early death in 1931 was remembered by name on the front page
      of Acta since 1936 by the Latin phrase 'A K.K.K. Lundsgaard edi coepta'. The
      present review recalls details from the early years when the journal found its
      place in the ophthalmology and creates the background for some reflections on
      purpose and goals by publishing a scientific journal.

PMID- 22136431
TI  - Affinity for risky behaviors following prenatal and early childhood exposure to
      tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort
      study.
AB  - BACKGROUND: Many studies of adults with acute and chronic solvent exposure have
      shown adverse effects on cognition, behavior and mood. No prior study has
      investigated the long-term impact of prenatal and early childhood exposure to the
      solvent tetrachloroethylene (PCE) on the affinity for risky behaviors, defined as
      smoking, drinking or drug use as a teen or adult. OBJECTIVES: This retrospective
      cohort study examined whether early life exposure to PCE-contaminated drinking
      water influenced the occurrence of cigarette smoking, alcohol consumption, and
      drug use among adults from Cape Cod, Massachusetts. METHODS: Eight hundred and
      thirty-one subjects with prenatal and early childhood PCE exposure and 547
      unexposed subjects were studied. Participants completed questionnaires to gather
      information on risky behaviors as a teenager and young adult, demographic
      characteristics, other sources of solvent exposure, and residences from birth
      through 1990. PCE exposure was estimated using the U.S. EPA's water distribution
      system modeling software (EPANET) that was modified to incorporate a leaching and
      transport model to estimate PCE exposures from pipe linings. RESULTS: Individuals
      who were highly exposed to PCE-contaminated drinking water during gestation and
      early childhood experienced 50-60% increases in the risk of using two or more
      major illicit drugs as a teenager or as an adult (Relative Risk (RR) for teen use
      = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9). Specific
      drugs for which increased risks were observed included crack/cocaine,
      psychedelics/hallucinogens, club/designer drugs, Ritalin without a prescription,
      and heroin (RRs:1.4-2.1). Thirty to 60% increases in the risk of certain smoking
      and drinking behaviors were also seen among highly exposed subjects. CONCLUSIONS:
      The results of this study suggest that risky behaviors, particularly drug use,
      are more frequent among adults with high PCE exposure levels during gestation and
      early childhood. These findings should be confirmed in follow-up investigations
      of other exposed populations.

PMID- 22136434
TI  - Ring-hydroxylating dioxygenase (RHD) expression in a microbial community during
      the early response to oil pollution.
AB  - The early functional response of a bacterial community from the sediments of a
      chronically oil-polluted retention basin located at the Etang de Berre (France)
      was investigated just after petroleum addition. After removing hydrocarbon
      compounds by natural abiotic and biotic processes, the sediments were maintained
      in microcosms and Vic Bilh petroleum was added. The diversity and the expression
      of genes encoding ring-hydroxylating dioxygenases (RHD) were examined just after
      the petroleum addition until 14 days focussing on the first hours following the
      contamination. RHD gene copy numbers and diversity were maintained throughout all
      the incubation period; however, transcripts were detected only during the first 2
      days. One dominant RHD gene, immediately and specifically expressed in response
      to petroleum contamination, was related to RHD gene carried by a plasmid found in
      Pseudomonas spp. The expression of the RHD genes was correlated with high
      biodegradation levels observed for low molecular weight PAHs at 7 days of
      incubation. The study shows that the bacterial metabolism induced just after the
      oil input is a key stage that could determine the bacterial community structure
      changes. Monitoring the expression of RHD genes, key genes involved in
      hydrocarbon degradation, may provide useful information for managing
      bioremediation processes.

PMID- 22136433
TI  - 7,8-dichloro-1-oxo-beta-carbolines as a versatile scaffold for the development of
      potent and selective kinase inhibitors with unusual binding modes.
AB  - Development of both potent and selective kinase inhibitors is a challenging task
      in modern drug discovery. The innate promiscuity of kinase inhibitors largely
      results from ATP-mimetic binding to the kinase hinge region. We present a novel
      class of substituted 7,8-dichloro-1-oxo-beta-carbolines based on the distinct
      structural features of the alkaloid bauerine C whose kinase inhibitory activity
      does not rely on canonical ATP-mimetic hinge interactions. Intriguingly,
      cocrystal structures revealed an unexpected inverted binding mode and the
      presence of halogen bonds with kinase backbone residues. The compounds exhibit
      excellent selectivity over a comprehensive panel of human protein kinases while
      inhibiting selected kinases such as the oncogenic PIM1 at low nanomolar
      concentrations. Together, our biochemical and structural data suggest that this
      scaffold may serve as a valuable template for the design and development of
      specific inhibitors of various kinases including the PIM family of kinases, CLKs,
      DAPK3 (ZIPK), BMP2K (BIKE), and others.

PMID- 22136435
TI  - The MLH1 2101C>A (Q701K) variant increases the risk of gastric cancer in Chinese
      males.
AB  - BACKGROUND: Gastric cancer is one of the most common cancers affecting East
      Asians, and MLH1 could play a critical role during tumorigenesis in this
      condition. METHODS: Samples from 236 Chinese patients suffering from gastric
      cancer were screened for MLH1 germline mutations. Carrier frequencies of the
      mutations were compared between gastric cancer patients and 240 cancer-free
      controls. Bioinformatic analysis was used to predict the effect of these
      mutations on protein function and mRNA splicing. RESULTS: Six MLH1 sequence
      alterations were identified in gastric cancer patients including two promoter
      region substitutions, -93G>A and -28A>G, and four missense mutations 649C>T
      (R217C), 655A>G (I219V), 1151T>A (V384D) and 2101C>A (Q701K). Compared with the
      MLH1 2101CC genotype, the 2101CA genotype was associated with a risk of gastric
      cancer (OR = 8.42, 95% CI = 1.04-68.06) in males. Furthermore, the MLH1 2101C>A
      mutant was predicted by in silico analysis to affect exon splicing ability.
      Immunohistochemistry of one index patient carrying the MLH1 2101C>A mutation
      demonstrated a loss of MLH1 protein and normal expression of MSH2 and E-cadherin.
      No significant differences were demonstrated between cases and controls for the
      other five MLH1 variants but the data indicated an ethnic difference in the
      frequency of these variations between Eastern Asians and Western populations.
      CONCLUSIONS: An ethnic-specific MLH1 mutation spectrum occurred in Chinese
      gastric cancer patients. The MLH1 2101C>A mutation could be a marker for
      susceptibility to gastric cancer, particularly in males.

PMID- 22136437
TI  - Ionic liquids-based extraction: a promising strategy for the advanced nuclear
      fuel cycle.

PMID- 22136436
TI  - Benralizumab--a humanized mAb to IL-5Ralpha with enhanced antibody-dependent cell
      mediated cytotoxicity--a novel approach for the treatment of asthma.
AB  - INTRODUCTION: Benralizumab is a monoclonal antibody that binds the alpha subunit
      of the receptor to IL-5. As IL-5 is implicated in disease states that are
      mediated by eosinophils, benralizumab is an attractive option for use in the
      management of asthma. As a result of enhanced antibody-directed cell
      cytotoxicity, it has enhanced eosinophil-depleting activity as compared with
      neutralizing monoclonal antibody directed against IL-5. AREAS COVERED: This
      review presents the available data on benralizumab, including pharmacodynamics,
      pharmacokinetics, preclinical data and relevant clinical studies. EXPERT OPINION:
      Our review indicates that although further investigation is necessary to
      demonstrate clinical benefit, benralizumab remains a promising treatment
      modality.

PMID- 22136441
TI  - The burden of chronic low back pain with and without a neuropathic component: a
      healthcare resource use and cost analysis.
AB  - BACKGROUND: This research addresses the need for population-based studies on the
      burden of chronic low back pain (CLBP) by examining healthcare service use and
      costs for patients with and without neuropathic components in the US population.
      METHODS: Data were analyzed from PharMetrics IMS LifeLinkTM US Claims Database
      (2006-2008). Patients (>=18 years) with 36 months continuous enrollment, ICD-9
      code for low back pain, and claims in 3 out of 4 consecutive months in the 12
      month prospective period were included and classified with CLBP. Patients were
      further classified with a neuropathic component (wNP) and without a neuropathic
      component (woNP) based on ICD-9 codes. Healthcare resources, physical therapy,
      prescription medication use, and associated costs were assessed for the period
      January 1-December 31, 2008. RESULTS: A number of patients (39,425) were
      identified with CLBP (90.4% wNP). Patients wNP included more women, were older
      and more likely to have clinically diagnosed depression, and made significantly
      greater use of any prescription medication at index event, opioids (particularly
      schedule II), and healthcare resources. Total direct costs of CLBP-related
      resource use were ~US$96 million over a 12-month follow-up. CLBP wNP accounted
      for 96% of total costs and mean annual cost of care/patient was ~160% higher than
      CLBP patients woNP (US$ 2577 vs US$ 1007, p < 0.0001). LIMITATIONS: This study
      was descriptive and was not designed to demonstrate causality between diagnosis,
      treatment, and outcomes. Resource use and costs for reasons other than LBP were
      not included. Patients with neuropathic pain are more likely to seek treatment;
      therefore CLBP patients with a non-neuropathic component may be under
      represented. CONCLUSIONS: The disproportionately high share of interventional
      resource use in CLBP wNP suggests greater need for new treatment options that
      more comprehensively manage the range of pain symptoms and signaling mechanisms
      involved, to help improve patient outcomes and reduce the burden on healthcare
      systems.

PMID- 22136442
TI  - An ethnobotanical survey of medicinal plants of Laos toward the discovery of
      bioactive compounds as potential candidates for pharmaceutical development.
AB  - CONTEXT: An ethnobotany-based approach in the selection of raw plant materials to
      study was implemented. OBJECTIVE: To acquire raw plant materials using
      ethnobotanical field interviews as starting point to discover new bioactive
      compounds from medicinal plants of the Lao People's Democratic Republic. METHODS:
      Using semi-structured field interviews with healers in the Lao PDR, plant samples
      were collected, extracted, and bio-assayed to detect bioactivity against cancer,
      HIV/AIDS, TB, malaria. Plant species demonstrating activity were recollected and
      the extracts subjected to a bioassay-guided isolation protocol to isolate and
      identify the active compounds. RESULTS: Field interviews with 118 healers in 15
      of 17 provinces of Lao PDR yielded 753 collections (573 species) with 955 plant
      samples. Of these 955, 50 extracts demonstrated activity in the anticancer, 10 in
      the anti-HIV, 30 in the anti-TB, and 52 in the antimalarial assay. Recollection
      of actives followed by bioassay-guided isolation processes yielded a series of
      new and known in vitro-active anticancer and antimalarial compounds from 5
      species. DISCUSSION: Laos has a rich biodiversity, harboring an estimated 8000
      11,000 species of plants. In a country highly dependent on traditional medicine
      for its primary health care, this rich plant diversity serves as a major source
      of their medication. CONCLUSIONS: Ethnobotanical survey has demonstrated the
      richness of plant-based traditional medicine of Lao PDR, taxonomically and
      therapeutically. Biological assays of extracts of half of the 955 samples
      followed by in-depth studies of a number of actives have yielded a series of new
      bioactive compounds against the diseases of cancer and malaria.

PMID- 22136444
TI  - Too late to say it is too early--how to get children with non-cirrhotic metabolic
      diseases transplanted at the right time?

PMID- 22136443
TI  - Model-based clustering reveals vitamin D dependent multi-centrality hubs in a
      network of vitamin-related proteins.
AB  - BACKGROUND: Nutritional systems biology offers the potential for comprehensive
      predictions that account for all metabolic changes with the intricate biological
      organization and the multitudinous interactions between the cellular proteins.
      Protein-protein interaction (PPI) networks can be used for an integrative
      description of molecular processes. Although widely adopted in nutritional
      systems biology, these networks typically encompass a single category of
      functional interaction (i.e., metabolic, regulatory or signaling) or nutrient.
      Incorporating multiple nutrients and functional interaction categories under an
      integrated framework represents an informative approach for gaining system level
      insight on nutrient metabolism. RESULTS: We constructed a multi-level PPI network
      starting from the interactions of 200 vitamin-related proteins. Its final size
      was 1,657 proteins, with 2,700 interactions. To characterize the role of the
      proteins we computed 6 centrality indices and applied model-based clustering. We
      detected a subgroup of 22 proteins that were highly central and significantly
      related to vitamin D. Immune system and cancer-related processes were strongly
      represented among these proteins. Clustering of the centralities revealed a
      degree of redundancy among the indices; a repeated analysis using subsets of the
      centralities performed well in identifying the original set of 22 most central
      proteins. CONCLUSIONS: Hierarchical and model-based clustering revealed multi
      centrality hubs in a vitamin PPI network and redundancies among the centrality
      indices. Vitamin D-related proteins were strongly represented among network hubs,
      highlighting the pervasive effects of this nutrient. Our integrated approach to
      network construction identified promiscuous transcription factors, cytokines and
      enzymes - primarily related to immune system and cancer processes - representing
      potential gatekeepers linking vitamin intake to disease.

PMID- 22136445
TI  - Gel-induced selective crystallization of polymorphs.
AB  - Although nanoporous materials have been explored for controlling crystallization
      of polymorphs in recent years, polymorphism in confined environments is still
      poorly understood, particularly from a kinetic perspective, and the role of the
      local structure of the substrate has largely been neglected. Herein, we report
      the use of a novel material, polymer microgels with tunable microstructure, for
      controlling polymorph crystallization from solution and for investigating
      systematically the effects of nanoconfinement and interfacial interactions on
      polymorphic outcomes. We show that the polymer microgels can improve polymorph
      selectivity significantly. The polymorphic outcomes correlate strongly with the
      gel-induced nucleation kinetics and are very sensitive to both the polymer
      microstructure and the chemical composition. Further mechanistic investigations
      suggest that the nucleation-templating effect and the spatial confinement imposed
      by the polymer network may be central to achieving polymorph selectivity. We
      demonstrate polymer microgels as promising materials for controlling crystal
      polymorphism. Moreover, our results help advance the fundamental understanding of
      polymorph crystallization at complex interfaces, particularly in confined
      environments.

PMID- 22136446
TI  - Intraurban mobility and its potential impact on the spread of blood-borne
      infections among drug injectors in Tijuana, Mexico.
AB  - We explored intraurban mobility of Tijuana, Mexico, injection drug users (IDUs).
      In 2005, 222 IDUs underwent behavioral surveys and infectious disease testing.
      Participants resided in 58 neighborhoods, but regularly injected in 30. From
      logistic regression, "mobile" IDUs (injecting >=3 km from their residence) were
      more likely to cross the Mexico/U.S. border, share needles, and get arrested for
      carrying syringes-but less likely to identify hepatitis as an injection risk.
      Mobile participants lived in neighborhoods with less drug activity, treatment
      centers, or migrants, but higher marriage and home ownership rates. Mobile IDUs
      should be targeted for outreach and further investigation. The study's
      limitations are noted.

PMID- 22136447
TI  - Structure-behavior-property relationship study of surfactants as foam stabilizers
      explored by experimental and molecular simulation approaches.
AB  - A multiscale stability study of foams stabilized by sodium dodecyl sulfate (SDS),
      sodium dodecylbenzene sulfonate (SDBS), and sodium polyoxyethylene alkylether
      sulfate (AES) was conducted, to investigate the relationship of surfactant
      molecular behavior and interfacial monolayer configuration of foam film to the
      foam film properties. Molecular dynamic (MD) simulations using a full-atom model
      was utilized to explore the microscopic features of the air/liquid interface
      layer. Several parameters such as the distribution of surfactant head groups and
      the order degree of surfactant hydrophobic tails were used to describe the
      molecular adsorption behavior. The effect of molecular structure on the nature of
      the foam film and the impact on the dynamic stability of wet foam is discussed.
      In the experimental evaluation, the SDBS foam films manifest strong stiffness and
      low viscoelasticity as shown by the interfacial shear rheology determination as
      well as texture analyzer (TA) measurement results, which agree very well with the
      array behavior of SDBS molecules at the air/water interface as described by the
      simulation results and is identified to be the reason for the poor dynamic
      stability. Comparing the molecular structure of SDS, SDBS, and AES, the special
      contributions of the linking groups such as the O atom, the phenyl group, and the
      EO (oxyethyl) chain to the interfacial array behavior of surfactants were
      characterized. It is concluded that microhardness of the foam film enhanced by
      rigid linking groups favors static foam stability but decreases the dynamic foam
      stability, while viscoelasticity of the foam film enhanced by soft linking groups
      increases the dynamic foam stability.

PMID- 22136448
TI  - Canine obesity--weighing on the mind of the owner?

PMID- 22136449
TI  - Thromboelastographic profile for a dog with hypocoagulable and hyperfibrinolytic
      phase of disseminated intravascular coagulopathy.
AB  - The objective of this study is to report the use of thromboelastography as a
      diagnostic tool for the hyperfibrinolytic phase of disseminated intravascular
      coagulopathy in a dog with metastatic haemangiosarcoma. We established a
      cytological (i.e. fine needle aspirate) and histopathological (i.e. excisional
      surgical biopsy) diagnosis of haemangiosarcoma in a 10-year-old male castrated
      Bichon Frise with multiple dark purple dermoepidermal nodules on the ventral
      abdomen and medial stifle areas, multiple small pulmonary nodules and a solitary
      liver mass. The dog was treated with chemotherapy (AC protocol). Forty-nine days
      after completion of four treatment cycles, the dog was presented for recheck.
      Complete blood count revealed anaemia and mild thrombocytopenia. Chemistry
      profile showed no significant abnormalities. Analysis of haemostasis consisted of
      prolonged clotting times (prothrombin time, activated partial thromboplastin
      time), mild hypofibrinogenaemia and increased D-dimers. A presumptive diagnosis
      of disseminated intravascular coagulopathy was made. A re-calcified
      thromboelastography was simultaneously done to confirm the coagulopathy.
      Thromboelastographic tracings correlated with the plasma-based test results
      showing hypocoagulability (prolonged clotting times and prolonged
      thromboelastography clot kinetics; weaker clot with decreased fibrinogen levels,
      platelet count and lower thromboelastography tracing amplitude) and
      hyperfibrinolysis (increased D-dimers and increased D-dimers and increased
      thromboelastography lysis parameters). Based on these results, the dog was
      considered to be in the hyperfibrinolytic phase of disseminated intravascular
      coagulopathy. Results of the conventional haemostasis tests supported those
      obtained on thromboelastography. Humane euthanasia was performed because of poor
      prognosis and progressive disease, making further follow-up unavailable. As
      demonstrated in this case report, thromboelastography was found to be a helpful
      diagnostic tool for the diagnosis and monitoring of the hyperfibrinolytic phases
      of disseminated intravascular coagulopathy.

PMID- 22136450
TI  - Nasal polyps in dogs: five cases (2005 to 2011).
AB  - This series describes five dogs with nasal polyps diagnosed between 2000 and
      2011. Clinical signs included reverse sneezing, nasal discharge, epistaxsis, and
      stertor when breathing. Computerised tomographic findings included soft tissue
      mass, turbinate destruction, extension through the bony nasal septum and partial
      lysis of bones surrounding the nasal cavity. Three dogs were treated by dorsal
      rhinotomy, one dog was treated by ventral rhinotomy, and in one dog the polyp
      tissue was removed during nasal flushing. Three dogs have no clinical signs of
      nasal disease. One dog had confirmed recurrence of nasal polyps and was
      successfully treated with megavoltage radiation. One dog had recurrent nasal
      disease eight months after dorsal rhinotomy. Nasal polyps are a possible cause of
      nasal disease in dogs with nasal discharge, epistaxsis and stertor, and a
      differential diagnosis for dogs with extensive soft tissue lesions of the nasal
      cavities on computerised tomography. Nasal polyps can be treated successfully by
      rhinotomy in some cases but may reoccur.

PMID- 22136451
TI  - Cavitating pulmonary lesions in German shepherd dogs.

PMID- 22136452
TI  - Histiocytic sarcoma of the urinary bladder in a dog.

PMID- 22136453
TI  - Femoral head and/or neck disease in cats: a histopathological investigation into
      the disease(s) involved.

PMID- 22136455
TI  - Progressive multifocal leukoencephalopathy: a review of the neuroimaging features
      and differential diagnosis.
AB  - Progressive multifocal leukoencephalopathy (PML) is an uncommon and often fatal
      demyelinating disease of human central nervous system, which is caused by
      reactivation of the polyomavirus JC (JCV). PML generally occurs in patients with
      profound immunosuppression such as AIDS patients. Recently, a number of PML cases
      have been associated with administration of natalizumab for treatment of multiple
      sclerosis (MS) patients. Diagnosis and management of PML became a major concern
      after its occurrence in multiple sclerosis patients treated with natalizumab.
      Diagnosis of PML usually rests on neuroimaging in the appropriate clinical
      context and is further confirmed by cerebrospinal fluid polymerase chain reaction
      (PCR) for JCV DNA. Treatment with antiretroviral therapies in HIV-seropositive
      patients or discontinuing natalizumab in MS patients with PML may lead to the
      development of immune reconstitution inflammatory syndrome (IRIS) which presents
      with deterioration of the previous symptoms and may lead to death. In patients
      under treatment with monoclonal antibodies in routine practice, or new ones in
      ongoing clinical trials, differentiating PML from new MS lesions on brain MRI is
      critical for both the neurologists and neuroradiologists. In this review, we
      discuss the clinical features, neuroimaging manifestations of PML, IRIS and
      neuroimaging clues to differentiate new MS lesions from PML. In addition, various
      neuroimaging features of PML on the non-conventional MR techniques such as
      diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and MR
      spectroscopy (MRS) are discussed.

PMID- 22136456
TI  - Health-related quality of life, sleep quality, and depression in peritoneal
      dialysis and hemodialysis patients.
AB  - Health-related quality of life (HRQoL) and sleep quality (SQ) were impaired in
      patients with end-stage renal disease (ESRD). The impairment of both HRQoL and SQ
      and being in a depressive mood were found to be associated with increased
      morbidity and mortality in dialysis patients. We aimed to investigate the
      association between SQ, HRQoL, and depression, and to define independent
      predictors of SQ and depression in peritoneal dialysis (PD) and hemodialysis (HD)
      patients. Ninety HD patients (41 females, 49 males with mean age 50 +/- 15.7
      years) and 64 PD patients (27 females, 37 males with mean age 52.4 +/- 15.3
      years) receiving renal replacement therapy for at least 3 months were screened
      for the assessment of SQ, HRQoL, and depression in this cross-sectional study. A
      modified postsleep inventory, Short Form of Medical Outcomes Study (SF-36) and
      Beck depression inventory (BDI) were applied to all patients for evaluating SQ,
      HRQoL, and depression, respectively. HD and PD patients had similar total SQ
      scores. Physical and mental component scale of HRQoL were found to be
      significantly higher in HD patients (p < 0.001). PD patients were found to be
      much more in depressive mood when compared with HD patients (p < 0.001).
      Independent predictors of depression in patients were mental component scale of
      HRQoL, gender (being female), and dialysis modality (being PD patient). Physical
      component scale was also found to be an independent predictor of SQ. This study
      showed that despite similar SQ scores between two groups, HD patients had better
      HRQoL and less depression than PD patients.

PMID- 22136457
TI  - Nucleation and island growth of alkanethiolate ligand domains on gold
      nanoparticles.
AB  - The metal oxide cluster alpha-AlW(11)O(39)(9-) (1), readily imaged by cryogenic
      transmission electron microscopy (cryo-TEM), is used as a diagnostic protecting
      anion to investigate the self-assembly of alkanethiolate monolayers on
      electrostatically stabilized gold nanoparticles in water. Monolayers of 1 on 13.8
      +/- 0.9 nm diameter gold nanoparticles are displaced from the gold surface by
      mercaptoundecacarboxylate, HS(CH(2))(10)CO(2)(-) (11-MU). During this process, no
      aggregation is observed by UV-vis spectroscopy, and the intermediate ligand-shell
      organizations of 1 in cryo-TEM images indicate the presence of growing
      hydrophobic domains, or "islands", of alkanethiolates. UV-vis spectroscopic
      "titrations", based on changes in the surface plasmon resonance upon exchange of
      1 by thiol, reveal that the 330 +/- 30 molecules of 1 initially present on each
      gold nanoparticle are eventually replaced by 2800 +/- 30 molecules of 11-MU. UV
      vis kinetic data for 11-MU-monolayer formation reveal a slow phase, followed by
      rapid self-assembly. The Johnson, Mehl, Avrami, and Kolmogorov model gives an
      Avrami parameter of 2.9, indicating continuous nucleation and two-dimensional
      island growth. During nucleation, incoming 11-MU ligands irreversibly displace 1
      from the Au-NP surface via an associative mechanism, with k(nucleation) = (6.1 +/
      0.4) * 10(2) M(-1) s(-1), and 19 +/- 8 nuclei, each comprised of ca. 8
      alkanethiolates, appear on the gold-nanoparticle surface before rapid growth
      becomes kinetically dominant. Island growth is also first-order in [11-MU], and
      its larger rate constant, k(growth), (2.3 +/- 0.2) * 10(4) M(-1) s(-1), is
      consistent with destabilization of molecules of 1 at the boundaries between the
      hydrophobic (alkanethiolate) and the electrostatically stabilized (inorganic)
      domains.

PMID- 22136458
TI  - RNA-seq in grain unveils fate of neo- and paleopolyploidization events in bread
      wheat (Triticum aestivum L.).
AB  - BACKGROUND: Whole genome duplication is a common evolutionary event in plants.
      Bread wheat (Triticum aestivum L.) is a good model to investigate the impact of
      paleo- and neoduplications on the organization and function of modern plant
      genomes. RESULTS: We performed an RNA sequencing-based inference of the grain
      filling gene network in bread wheat and identified a set of 37,695 non-redundant
      sequence clusters, which is an unprecedented resolution corresponding to an
      estimated half of the wheat genome unigene repertoire. Using the Brachypodium
      distachyon genome as a reference for the Triticeae, we classified gene clusters
      into orthologous, paralogous, and homoeologous relationships. Based on this wheat
      gene evolutionary classification, older duplicated copies (dating back 50 to 70
      million years) exhibit more than 80% gene loss and expression divergence while
      recent duplicates (dating back 1.5 to 3 million years) show only 54% gene loss
      and 36 to 49% expression divergence. CONCLUSIONS: We suggest that structural
      shuffling due to duplicated gene loss is a rapid process, whereas functional
      shuffling due to neo- and/or subfunctionalization of duplicates is a longer
      process, and that both shuffling mechanisms drive functional redundancy erosion.
      We conclude that, as a result of these mechanisms, half the gene duplicates in
      plants are structurally and functionally altered within 10 million years of
      evolution, and the diploidization process is completed after 45 to 50 million
      years following polyploidization.

PMID- 22136459
TI  - Positivity effect in healthy aging in observational but not active feedback
      learning.
AB  - The present study investigated the impact of healthy aging on the bias to learn
      from positive or negative performance feedback in observational and active
      feedback learning. In active learning, a previous study had already shown a
      negative learning bias in healthy seniors older than 75 years, while no bias was
      found for younger seniors. However, healthy aging is accompanied by a 'positivity
      effect', a tendency to primarily attend to stimuli with positive valence. Based
      on recent findings of dissociable neural mechanisms in active and observational
      feedback learning, the positivity effect was hypothesized to influence older
      participants' observational feedback learning in particular. In two separate
      experiments, groups of young (mean age 27) and older participants (mean age 60
      years) completed an observational or active learning task designed to
      differentially assess positive and negative learning. Older but not younger
      observational learners showed a significant bias to learn better from positive
      than negative feedback. In accordance with previous findings, no bias was found
      for active learning. This pattern of results is discussed in terms of differences
      in the neural underpinnings of active and observational learning from performance
      feedback.

PMID- 22136460
TI  - Soluble human leukocyte antigen-G expression in hepatitis B virus infection and
      hepatocellular carcinoma.
AB  - We investigated soluble human leukocyte antigen-G (sHLA-G) expression according
      to the phases of hepatitis B virus (HBV) infections and hepatocellular carcinoma
      (HCC). A total of 267 sera from anti-HBs positive healthy individuals (n = 50),
      chronic HBV carriers (n = 45), as well as patients with active hepatitis B (n =
      46), liver cirrhosis (LC, n = 46) and early stage HCC (n = 80) were collected and
      assayed for sHLA-G. Relationships between sHLA-G levels and clinicopathologic
      parameters including HCC stages, differentiation grades, and levels of
      aminotransferases, HBV DNA and alpha-fetoprotein (AFP) were assessed.
      Concentrations of sHLA-G were higher in the active hepatitis B and HCC groups
      (median sHLA-G 53.7 and 178.8 U/ml, respectively) in comparison to other groups
      (P < 0.05), and there were no significant differences among sHLA-G levels of the
      anti-HBs positive, chronic HBV carrier and LC groups. Serum sHLA-G concentrations
      were not shown to be associated with clinicopathologic indices including the
      levels of aminotransferases, AFP, anti-HBs titer, HBV DNA, as well as HCC stages,
      numbers of tumor nodules, pathologic grades and presence of vessel invasion. The
      receiver-operating characteristic area under the curve (AUC) value of sHLA-G for
      differentiating HCC from LC was 0.98, which was greater than that of AFP (0.78)
      (P < 0.0001), and sensitivity and specificity of sHLA-G were, respectively, 90.0%
      and 95.7% for HCC when applying a cutoff level of 97.3 U/ml. Serum sHLA-G levels
      could be used as a diagnostic marker for HCC. Although sHLA-G levels did not
      reflect the severity of HBV infections and HCC, they were related with phases of
      the disease.

PMID- 22136461
TI  - Cardiovascular importance of the microRNA-23/27/24 family.
AB  - MicroRNAs (miRNAs) are a class of highly conserved, noncoding short RNA molecules
      that regulate gene expression on the post-transcriptional level. MiRNAs are
      involved in a variety of processes such as proliferation, differentiation, and
      apoptosis. Deregulated expression of miRNAs has been linked to the development of
      diseases including cardiovascular disorders. Recently, the miR-23/27/24 cluster
      has been shown to be involved in angiogenesis and endothelial apoptosis in
      cardiac ischemia and retinal vascular development. In the present review, we
      summarize and discuss the role and importance of the miRNA-23/27/24 cluster
      during cardiovascular angiogenesis. Moreover, we illustrate a novel therapeutic
      application of the miRNA-23/27/24 cluster in vascular disorders and ischemic
      heart disease.

PMID- 22136464
TI  - DataBase: Research and Evaluation Results.

PMID- 22136462
TI  - Enhanced optical trapping and arrangement of nano-objects in a plasmonic
      nanocavity.
AB  - Gentle manipulation of micrometer-sized dielectric objects with optical forces
      has found many applications in both life and physical sciences. To further extend
      optical trapping toward the true nanometer scale, we present an original approach
      combining self-induced back action (SIBA) trapping with the latest advances in
      nanoscale plasmon engineering. The designed resonant trap, formed by a
      rectangular plasmonic nanopore, is successfully tested on 22 nm polystyrene
      beads, showing both single- and double-bead trapping events. The mechanism
      responsible for the higher stability of the double-bead trapping is discussed, in
      light of the statistical analysis of the experimental data and numerical
      calculations. Furthermore, we propose a figure of merit that we use to quantify
      the achieved trapping efficiency and compare it to prior optical nanotweezers.
      Our approach may open new routes toward ultra-accurate immobilization and
      arrangement of nanoscale objects, such as biomolecules.

PMID- 22136466
TI  - Endurance exercise is a leptin signaling mimetic in hypothalamus of Wistar rats.
AB  - BACKGROUND: Endurance exercise is known to promote a substantial effect on the
      energy balance in rats and humans. However, little is known about the exact
      mechanisms for the appetite-suppressive effects of endurance exercise. We
      hypothesized that endurance training might activate signaling cascades in the
      hypothalamus known to be involved in leptin signaling. METHODS: 16 male Wistar
      rats were randomly assigned to two groups: sedentary (n = 8) and exercise groups
      (n = 8). Animals in the exercise group started treadmill running at 30 m/min, 0%
      grade, for 1 min/bout. Running time was gradually increased by 2 min/bout every
      day. The training plan was one bout per day during initial two weeks, and two
      bouts per day during 3rd-9th week. At the end of nine-week experiment, blood was
      analyzed for low-density lipoprotein cholesterol (LDL-C), triglyceride (TG),
      total cholesterol (TC), free fatty acid (FFA), interleukin (IL)-6, and leptin in
      both groups. Activations of janus kinase 2-signaling transducer and activator of
      transcription 3 (JAK2-STAT3), protein kinase B (Akt), extracellular regulated
      kninase (ERKs), and suppressor of cytokine signaling 3 (SOCS3) in hypothalamus
      were measured in the end of nine weeks of exercise protocol. RESULTS: Nine-week
      endurance exercise induced lower concentrations of LDL-C, TG, TC, FFA, and leptin
      in rats (P < 0.05 or P < 0.01). Nine-week endurance exercise significantly
      increased the circulating IL-6 concentration compared with sedentary group (239.6
      +/- 37.2 pg/ml vs. 151.8 +/- 31.5 pg/ml, P < 0.01). Exercise rats showed
      significant increases in JAK2, STAT3, Akt, ERKs, and SOCS3 phosphorylations
      compared with sedentary rats (P < 0.01). CONCLUSION: The data suggest that
      endurance exercise is a leptin signaling mimetic in hypothalamus of Wistar rats.

PMID- 22136467
TI  - Clinical pathways in transplantation: a review and examples from Beth Israel
      Deaconess Medical Center.
AB  - Clinical pathways (CP) have been developed to aid in the management of many
      surgical and medical conditions. Studies show the benefits of CP on outcomes
      including reduction in length of stay (LOS), morbidity, costs, and improvement in
      patient satisfaction (Arch Surg 2008: 394: 31; J Eval Clin Pract 2007: 13: 920;
      Arch Otolaryngol Head Neck Surg 2000: 126: 322; Circulation 2000: 101: 461; BMC
      Pulm Med 2006: 6: 22; Int J Health Care Qual Assur 2006: 19: 237; Am J Med Qual
      2005: 20: 83; Am J Surg 2006: 192: 399; Am Surg 2005: 71: 152). Reports of CP in
      solid organ transplantation are lacking, possibly given the complexity of the
      transplant procedures that entail a complex, multidisciplinary pre-operative
      evaluation, inpatient, and post-operative time frames. We have developed CP from
      presentation for transplant evaluation to post-transplant follow-up for liver,
      kidney, and pancreas transplantation and live kidney and live liver donation and
      are making them available online for viewing. Our CPs encompass the pre
      operative, peri-operative, and post-operative period, including both outpatient
      and inpatient care. We propose that transplantation is an ideal forum for
      successful implementation of CP, given the rigorous process that centers are
      subject to for CMS approval and the ample opportunity for improving our patients'
      lives by improvement in and streamlining of the entire process of clinical care
      from end-stage organ failure to post-transplant long-term management. Our CPs can
      be found at
      http://bidmc.org/CentersandDepartments/Departments/TransplantInstitute/Transplant
      linicalPathways.aspx.

PMID- 22136468
TI  - Short wavelength light filtering by the natural human lens and IOLs --
      implications for entrainment of circadian rhythm.
AB  - PURPOSE: Photoentrainment of circadian rhythm begins with the stimulation of
      melanopsin containing retinal ganglion cells that respond directly to blue light.
      With age, the human lens becomes a strong colour filter attenuating transmission
      of short wavelengths. The purpose of the study was to examine the effect the
      ageing human lens may have for the photoentrainment of circadian rhythm and to
      compare with intraocular implant lenses (IOLs) designed to block UV radiation,
      violet or blue light. METHODS: The potential for photoentrainment of circadian
      rhythm was computed for 29 human donor lenses (18-76 years) and five IOLs (one
      UV, two violet and two blue light blocking) based on the transmission properties
      of the lenses and the spectral characteristics of melanopsin activation and two
      of it's physiological outcomes; melanopsin-driven pupillary light reponse and
      light-induced melatonin suppression. RESULTS: The potential for melanopsin
      stimulation and melatonin suppression was reduced by 0.6-0.7 percentage point per
      year of life because of yellowing of the natural lens. The computed effects were
      small for the IOLs and did not exceed that of a 22.2-year-old natural lens for
      the blue-blocking IOLs. CONCLUSION: The results show that photoentrainment of
      circadian rhythm may be significantly impaired in older subjects because of the
      colour filtering characteristics of the human lens, whereas the effects were
      small for all three types of IOLs studied. Consequently, the ageing process of
      the natural lens is expected to influence the photoentrainment of circadian
      rhythm, whereas IOLs are not expected to be detrimental to circadian rhythm.

PMID- 22136469
TI  - Fragment-based discovery of bromodomain inhibitors part 2: optimization of
      phenylisoxazole sulfonamides.
AB  - Bromodomains are epigenetic reader modules that regulate gene transcription
      through their recognition of acetyl-lysine modified histone tails. Inhibitors of
      this protein-protein interaction have the potential to modulate multiple diseases
      as demonstrated by the profound anti-inflammatory and antiproliferative effects
      of a recently disclosed class of BET compounds. While these compounds were
      discovered using phenotypic assays, here we present a highly efficient
      alternative approach to find new chemical templates, exploiting the abundant
      structural knowledge that exists for this target class. A phenyl dimethyl
      isoxazole chemotype resulting from a focused fragment screen has been rapidly
      optimized through structure-based design, leading to a sulfonamide series showing
      anti-inflammatory activity in cellular assays. This proof-of-principle experiment
      demonstrates the tractability of the BET family and bromodomain target class to
      fragment-based hit discovery and structure-based lead optimization.

PMID- 22136470
TI  - Greyhound-specific reference intervals: a good start to a long race.

PMID- 22136472
TI  - Successful immunostaining demonstrates abnormal intracytoplasmic MYH9 protein
      (NMMHC-IIA) in neutrophils of a dog with May-Hegglin anomaly.

PMID- 22136473
TI  - It's odd not to use odds.

PMID- 22136477
TI  - Flow cytometric assessment of canine erythrocytes and platelets for dog
      erythrocyte antigen 1.1.
AB  - BACKGROUND: In human medicine, transfusion of ABO-mismatched platelets has been
      associated with shortened platelet survival and refractoriness to platelet
      transfusion because of expression of certain blood group antigens on platelets.
      It remains unknown if canine platelets express dog erythrocyte antigens (DEAs).
      OBJECTIVE: The aim of this study was to develop a flow cytometric assay for DEA
      1.1 and determine whether DEA 1.1 is present on canine platelets. METHODS: Blood
      was collected from 172 clinically healthy dogs. Platelets and erythrocytes from
      each dog were tested for DEA 1.1 by flow cytometry using anti-DEA 1.1 blood
      typing sera. Erythrocytes from each dog were also assessed for DEA 1.1 using a
      standard tube-typing test (T1) and using a second tube method (T2), if the flow
      cytometric and T1 results differed. RESULTS: Using flow cytometry, DEA 1.1 was
      detected on erythrocytes of all 110 dogs shown by T1 or T2 testing to be DEA 1.1
      positive. Initial results of the T1 test had a diagnostic accuracy of 93% (160
      correct/172 tests). The frequency of erythrocyte DEA 1.1 positivity in previously
      untyped dogs (n = 118) was 56%. DEA 1.1 expression was not detected on platelets
      from DEA 1.1-positive dogs. CONCLUSIONS: Flow cytometry was a reliable method for
      detection of DEA 1.1 on canine erythrocytes. The absence of DEA 1.1 on platelets
      from DEA 1.1-positive dogs suggests that their platelets do not express DEA 1.1
      and will not induce production of anti-DEA 1.1 antibodies that might lead to
      platelet refractoriness or reactions to a subsequent transfusion of DEA 1.1
      positive erythrocytes.

PMID- 22136478
TI  - Frequency of dog erythrocyte antigen 1.1 in 4 breeds native to different areas in
      Turkey.
AB  - BACKGROUND: Dog erythrocyte antigen (DEA) 1.1 is the most important RBC antigen
      clinically, as it is highly immunogenic and causes acute hemolytic transfusion
      reactions (HTR) in sensitized dogs. OBJECTIVES: The aims of this study were to
      determine the frequency of DEA 1.1 expression in 4 Turkish dog breeds, and to
      estimate the potential risk of HTR when blood from a DEA 1.1-positive donor is
      administered to a DEA 1.1-negative recipient following sensitization by a prior
      mismatched transfusion. METHODS: EDTA blood samples (n = 178) were typed for DEA
      1.1 using a commercial gel-column agglutination test (ID-Gel-Test Canine DEA
      1.1). Probabilities of sensitization and risk of an HTR were calculated. RESULTS:
      The frequency of positivity for DEA 1.1 among Kars (n = 59), Kangal (n = 53),
      Akbash (n = 50), and Catalburun (n = 16) breeds was 71.2%, 67.9%, 60.0%, and
      50.0%, respectively. Potential risk for occurrence of an HTR after administration
      of blood from a dog of the same breed ranged from 12.5% to 14.8%, whereas HTR
      induced by blood of a dog from a different breed ranged from 7.2% to 25.3%.
      CONCLUSIONS: The frequency of DEA 1.1-positive dogs among 4 Turkish breeds is
      high compared with that of most other breeds previously surveyed. The predicted
      risk of both sensitization and occurrence of DEA 1.1-related HTR following
      transfusion between dogs of either the same or different Turkish breeds was
      considerable. Although few dogs are transfused >=4 days after the first
      transfusion, we recommend that (1) all donors and recipients be typed for DEA
      1.1, (2) DEA 1.1-negative recipients receive only DEA 1.1-negative blood, and (3)
      blood be cross-matched prior to transfusing any dog >=4 days after the first
      transfusion. These guidelines are also applicable to other breeds and countries.

PMID- 22136479
TI  - Granulomatous lymphadenitis caused by Talaromyces helicus in a Labrador
      Retriever.
AB  - A 3-year-old spayed female Labrador Retriever was presented for right prescapular
      lymphadenomegaly. Examination of fine-needle aspirates and impression smears of
      the node revealed many short hyphal structures found within macrophages and
      extracellularly. Hyphae were approximately 3 MUm in diameter, were irregularly
      septate with nonparallel walls, and had a small clear halo surrounding a
      partially stained basophilic internal structure. Hyphae were tapered on one end
      and had oval to pyriform swellings of 7-10 MUm on the other, resulting in a
      bulbous appearance. Fungal elements stained positively with Gomori methenamine
      silver and Periodic acid-Schiff stains. The dog was euthanized at the owner's
      request, and necropsy revealed marked peripheral and visceral lymphadenomegaly.
      Histopathologic examination of lymph nodes confirmed granulomatous lymphadenitis
      with many fungal hyphae. Fungal culture yielded pure cultures of organisms that
      failed to produce ascospores or conidia precluding morphologic identification.
      PCR was performed using pan-fungal primers, ITS-1 and ITS-2, to amplify the
      intergenic spacer regions of ribosomal RNA; the PCR product was sequenced and a
      BLAST search of the GenBank databases at NCBI revealed 100% identity of the
      organism with Talaromyces helicus, the sexual form of Penicillium helicum.
      Talaromyces helicus has not previously been reported to cause disease in people
      or animals.

PMID- 22136480
TI  - What is your diagnosis? Bone marrow aspirate from a hyacinth macaw (Anodorhynchus
      hyacinthinus).

PMID- 22136482
TI  - Development of validated stability-indicating chromatographic method for the
      determination of fexofenadine hydrochloride and its related impurities in
      pharmaceutical tablets.
AB  - A simple reversed phase high performance liquid chromatographic method with
      diode array detector (HPLC-DAD) has been developed and subsequently validated for
      the determination of fexofenadine hydrochloride (FEX) and its related compounds;
      keto fexofenadine (Impurity A), meta isomer of fexofenadine (Impurity B), methyl
      ester of fexofenadine (Impurity C) in addition to the methyl ester of
      ketofexofenadine (Impurity D). The separation was based on the use of a Hypersil
      BDS C-18 analytical column (250 * 4.6 mm, i.d., 5 MUm). The mobile phase
      consisted of a mixture of phosphate buffer containing 0.1 gm% of 1-octane
      sulphonic acid sodium salt monohydrate and 1% (v/v) of triethylamine, pH 2.7 and
      methanol (60:40, v/v). The separation was carried out at ambient temperature with
      a flow rate of 1.5 ml/min. Quantitation was achieved with UV detection at 215 nm
      using lisinopril as internal standard, with linear calibration curves at
      concentration ranges 0.1-50 MUg/ml for FEX and its related compounds. The
      optimized conditions were used to develop a stability-indicating HPLC-DAD method
      for the quantitative determination of FEX and its related compounds in tablet
      dosage forms. The drugs were subjected to oxidation, hydrolysis, photolysis and
      heat to apply stress conditions. Complete separation was achieved for the parent
      compounds and all degradation products. The method was validated according to ICH
      guidelines in terms of accuracy, precision, robustness, limits of detection and
      quantitation and other aspects of analytical validation.

PMID- 22136481
TI  - Rationale and design of the B-PROOF study, a randomized controlled trial on the
      effect of supplemental intake of vitamin B12 and folic acid on fracture
      incidence.
AB  - BACKGROUND: Osteoporosis is a major health problem, and the economic burden is
      expected to rise due to an increase in life expectancy throughout the world.
      Current observational evidence suggests that an elevated homocysteine
      concentration and poor vitamin B12 and folate status are associated with an
      increased fracture risk. As vitamin B12 and folate intake and status play a large
      role in homocysteine metabolism, it is hypothesized that supplementation with
      these B-vitamins will reduce fracture incidence in elderly people with an
      elevated homocysteine concentration. METHODS/DESIGN: The B-PROOF (B-Vitamins for
      the PRevention Of Osteoporotic Fractures) study is a randomized double-blind
      placebo-controlled trial. The intervention comprises a period of two years, and
      includes 2919 subjects, aged 65 years and older, independently living or
      institutionalized, with an elevated homocysteine concentration (>= 12 MUmol/L).
      One group receives daily a tablet with 500 MUg vitamin B12 and 400 MUg folic acid
      and the other group receives a placebo tablet. In both tablets 15 MUg (600 IU)
      vitamin D is included. The primary outcome of the study is osteoporotic
      fractures. Measurements are performed at baseline and after two years and cover
      bone health i.e. bone mineral density and bone turnover markers, physical
      performance and physical activity including falls, nutritional intake and status,
      cognitive function, depression, genetics and quality of life. This large multi
      center project is carried out by a consortium from the Erasmus MC (Rotterdam, the
      Netherlands), VUmc (Amsterdam, the Netherlands) and Wageningen University,
      (Wageningen, the Netherlands), the latter acting as coordinator. DISCUSSION: To
      our best knowledge, the B-PROOF study is the first intervention study in which
      the effect of vitamin B12 and folic acid supplementation on osteoporotic
      fractures is studied in a general elderly population. We expect the first
      longitudinal results of the B-PROOF intervention in the second semester of 2013.
      The results of this intervention will provide evidence on the efficacy of vitamin
      B12 and folate supplementation in the prevention of osteoporotic fractures. TRIAL
      REGISTRATION: The B-PROOF study is registered with the Netherlands Trial (NTR
      NTR1333) and with ClinicalTrials.gov (NCT00696514).

PMID- 22136483
TI  - Evaluation of IL18 and IL18R1 polymorphisms: genetic susceptibility to knee
      osteoarthritis.
AB  - We examined single-nucleotide polymorphisms (SNPs) in IL18 and IL18/R1 genes and
      knee OA. IL18 rs1946518 wild-type allele was more frequently observed in cases (P
      = 0.04). Haplotype 1 was more frequently observed in cases (P = 0.04). Genetic
      variation in the promoter region of IL18, but not IL18R1, may be associated with
      OA.

PMID- 22136484
TI  - Mercaptocarborane-capped gold nanoparticles: electron pools and ion traps with
      switchable hydrophilicity.
AB  - A simple single-phase method for the preparation of ca. 2 nm gold nanoparticles
      capped with mercaptocarborane ligands is introduced. The resultant monolayer
      protected clusters (MPCs) exhibit redox-dependent solubility and readily phase
      transfer between water and nonpolar solvents depending on the electronic and
      ionic charge stored in the metal core and in the ligand shell, respectively. The
      particles and their properties have been characterized by high angle annular dark
      field imaging in a scanning transmission electron microscope, elemental analysis,
      centrifugal particle sizing, UV-vis and FTIR spectroscopy, and thermogravimetric
      analysis and by (1)H, (11)B, and (7)Li NMR spectroscopy. Cellular uptake of the
      MPCs by HeLa cells has been studied by TEM, and the subsequent generation of
      reactive oxygen species inside the cells has been evaluated by confocal
      fluorescence microscopy. These MPCs qualitatively showed significant toxicity and
      the ability to penetrate into most cell compartments with a strong tendency of
      finally residing inside membranes. Applications in catalysis, electrocatalysis,
      and biomedicine are envisaged.

PMID- 22136485
TI  - Elicitation of utility scores in Canada for immune thrombocytopenia treated with
      romiplostim or watch and rescue.
AB  - OBJECTIVES: The objective of this study was to obtain utilities, or preference
      based quality-of-life values, from the Canadian general public, for potential
      health states experienced by immune thrombocytopenia (ITP) patients receiving
      either romiplostim (a new thrombopoietin mimetic agent) or 'watch and rescue'
      therapy. Utilities are needed to conduct a cost-utility analysis of romiplostim
      for formulary and reimbursement decisions. METHODS: An electronic Time Trade-off
      (TTO) survey was developed and administered to a sample of the general public in
      Canada, with 12 distinct health states derived from two randomized clinical
      trials of romiplostim vs watch and rescue treatment. Two pilot tests assessed
      interpretability and respondent burden. In the final survey, each subject was
      administered the TTO for four randomly-selected health states. Descriptive
      statistics were computed for utility scores, and differences between health
      states were evaluated with an analysis of variance model. RESULTS: Eight hundred
      and twenty-one adults completed the TTO survey. Mean age was 36.4 (SD = 15)
      years; 63% were female. Mean (SD) utility scores ranged from 0.476 (0.271) for
      the most severe health state (significant bleeding) to 0.633 (0.282) for the
      least severe health state depicting successful treatment with romiplostim.
      Statistical significance was found on the mean difference between the most severe
      health state and five other health states (p < 0.05). After adjusting utilities
      for matching Canadian demographic parameters, no substantial difference was found
      between original utility scores and adjusted scores. CONCLUSIONS: This study
      provides evidence of the Canadian general public's preference for 12 ITP health
      states pertaining to romiplostim treatment or watch and rescue. This study had a
      number of limitations, the main ones being the lack of perfect match in
      demographics between this sample and the Canadian population, as well as the fact
      that the scenario descriptions were based on both published literature and expert
      opinion. Despite those limitations, the obtained utility scores may be used in
      cost-utility models of romiplostim as a treatment for ITP patients in Canada.

PMID- 22136486
TI  - Molecular dynamics simulations of the supramolecular assembly between an
      azobenzene-containing surfactant and alpha-cyclodextrin: role of
      photoisomerization.
AB  - Control of the self-assembly and disassembly at the molecular level has become a
      subject of increasing activity. The supramolecular assembly between a
      photoswitchable azobenzene-containing surfactant, AzoC10, and alpha-cyclodextrin
      that combines photochemistry and host-guest chemistry for a stimulus-responsive
      vesicle has been recently reported. To clarify the role of photoisomerization in
      the reversible assembly and disassembly, we present in this work atomistic
      molecular dynamics simulations of the host-guest complexation of AzoC10 with
      alpha-cyclodextrin. The results of simulation reveal that both cis- and trans
      AzoC10 form the inclusion complexes with alpha-CD, but the binding modes are
      rather different. The azobenzene moiety of trans-AzoC10 is included at the center
      of the cavity of alpha-CD, whereas one of the phenyl rings of cis-AzoC10 is
      exposed to water and the other is included in the cavity of alpha-CD. The
      shuttling motion of alpha-CD over the long alkyl chain of cis-AzoC10 is observed
      in the simulations. The potentials of mean force calculated for AzoC10 to pass
      through the cavity of alpha-CD show that the host-guest assembly is basically
      downhill for trans-AzoC10, but an energy barrier has to be overcome for cis
      AzoC10 to complex with alpha-CD.

PMID- 22136487
TI  - Analysis of BK viral infection after alemtuzumab induction for renal transplant.
AB  - Induction immunosuppression has provided great advances in reducing the incidence
      of acute rejection (AR) following kidney transplantation. Despite this success,
      there has been recent concern over possible increased rates of viral
      complications when such powerful immunosuppressive therapy is used. This study
      was undertaken to determine the incidence of BK viral infection following kidney
      transplantation under alemtuzumab induction therapy. METHODS: With institutional
      review board approval, a retrospective study was performed of all patients
      undergoing kidney transplantation under alemtuzumab induction at a single center.
      The incidence of BK viremia was determined, and univariate analysis was performed
      to determine factors associated with the development of BK viremia. Further
      analysis was undertaken, using standard statistical methods, to determine the
      rates of graft survival and hazard ratio (HR) for AR in patients with and without
      BK viremia. RESULTS: There were 456 patients in the current study, with a mean
      age of 51 years. The majority of these (61.8%) were male, and 73.5% were
      Caucasian. The overall incidence of BK viremia identified on routine screening
      was 6.6%. Univariate analysis failed to identify any significant predictors of BK
      viremia. One-, 3-, and 5-year graft survival for patients who developed BK
      viremia was 96.6%, 91.7%, and 91.7%, respectively, compared with 94.1%, 87.8%,
      and 80.2% for patients without BK viremia (P = 0.860). BK viremia was associated
      with a significantly increased risk for AR (HR 3.48, 95% confidence interval 1.24
      9.76; P = 0.018). CONCLUSION: The incidence of BK viremia following alemtuzumab
      induction appears to be in concordance with the published literature, with
      satisfactory graft survival rates. BK viremia is, however, associated with an
      increased risk for AR.

PMID- 22136488
TI  - Tigecycline penetration into skin and soft tissue.
AB  - BACKGROUND: Tigecycline, a derivative of minocycline, has antibacterial activity
      against common pathogens associated with complicated skin and soft tissue
      infections (cSSTIs), including methicillin-resistant Staphylococcus aureus. At
      present, there is a paucity of data concerning its penetration into skin and soft
      tissue (SST). METHODS: This study evaluated the penetration of tigecycline into
      SST in 25 patients (mean age, 52 years) with cSSTIs requiring surgical
      intervention. After a 100-mg loading dose, each patient received 50 mg of
      tigecycline infused intravenously over 1 h every 12 h. Blood samples were
      obtained on the day of surgery at 1 h (peak), during surgery, and 12 h (trough)
      after the beginning of a 50-mg infusion. A viable SST sample was harvested at the
      infection site. Tissue and concomitant serum concentrations were grouped into
      three time intervals: 2-4 h (median, 3 h), 5-7 h (median, 7 h), and 8-10 h
      (median, 9h), and analyzed for tissue penetration. RESULTS: Tissue and blood
      samples were obtained one to six days (mean 2.5 days) after initiation of
      tigecycline treatment. The mean serum peak and trough concentrations of
      tigecycline were 0.56+/-0.25 mg/L and 0.26+/-0.12 mg/L, respectively. The mean
      tissue:serum ratios at the three study time periods were 3.8 (range 0.7-5.5), 5.2
      (range 0.8-7.1), and 2.8 (range 0.8-8.8). CONCLUSIONS: In general, we found
      higher concentrations of tigecycline in SST than in the serum at the same time
      point.

PMID- 22136490
TI  - Use of an antimicrobial skin sealant reduces surgical site infection in patients
      undergoing routine cardiac surgery.
AB  - BACKGROUND: With high morbidity and potentially devastating consequences,
      surgical site infections (SSIs) after cardiac surgery add substantially to the
      healthcare burden. Inhibiting migration of skin microbes is likely to reduce
      contamination of the surgical incision by endogenous potential pathogens. We
      studied the effect of treatment with a cyanoacrylate-based antimicrobial skin
      sealant (INTEGUSEAL(r)) on the SSI rate in cardiac surgery patients. METHODS: In
      a consecutive series of 910 prospective patients undergoing routine cardiac
      surgery, standard pre-operative preparation was performed on 721 patients of whom
      189 also received antimicrobial skin sealant. A further 189 consecutive patients
      who received only standard pre-operative care were studied retrospectively. The
      primary study endpoint was occurrence of superficial or deep SSI according to the
      definitions of the U.S. Centers for Disease Control and Prevention. RESULTS: The
      mean (standard deviation) SSI risk score based on combined pre-operative and
      intra-operative factors according to the Society of Thoracic Surgeons risk
      scoring system was significantly higher for the skin sealant group (9.1+/-1.0)
      than for the prospective (7.1+/-3.2; p<0.001) and retrospective (8.7+/-0.8;
      p<0.001) control groups. Surgical site infections occurred in two patients (1.1%)
      in the sealant group, 33 patients (4.6%) in the prospective control group
      (p<0.025), and nine patients (4.8%) in the retrospective control group (p<0.032).
      CONCLUSIONS: When added to existing pre-operative measures to reduce bacterial
      contamination of surgical incisions that are employed routinely at this
      cardiovascular surgery unit, use of antimicrobial skin sealant decreased the
      incidence of SSI in cardiac surgery patients.

PMID- 22136489
TI  - Comparison of two computer algorithms to identify surgical site infections.
AB  - BACKGROUND: Surgical site infections (SSIs), the second most common healthcare
      associated infections, increase hospital stay and healthcare costs significantly.
      Traditional surveillance of SSIs is labor-intensive. Mandatory reporting and new
      non-payment policies for some SSIs increase the need for efficient and
      standardized surveillance methods. Computer algorithms using administrative,
      clinical, and laboratory data collected routinely have shown promise for
      complementing traditional surveillance. METHODS: Two computer algorithms were
      created to identify SSIs in inpatient admissions to an urban, academic tertiary
      care hospital in 2007 using the International Classification of Diseases, Ninth
      Revision, Clinical Modification (ICD-9-CM) diagnosis codes (Rule A) and
      laboratory culture data (Rule B). We calculated the number of SSIs identified by
      each rule and both rules combined and the percent agreement between the rules. In
      a subset analysis, the results of the rules were compared with those of
      traditional surveillance in patients who had undergone coronary artery bypass
      graft surgery (CABG). RESULTS: Of the 28,956 index hospital admissions, 5,918
      patients (20.4%) had at least one major surgical procedure. Among those and
      readmissions within 30 days, the ICD-9-CM-only rule identified 235 SSIs, the
      culture-only rule identified 287 SSIs; combined, the rules identified 426 SSIs,
      of which 96 were identified by both rules. Positive and negative agreement
      between the rules was 36.8% and 97.1%, respectively, with a kappa of 0.34 (95%
      confidence interval [CI] 0.27-0.41). In the subset analysis of patients who
      underwent CABG, of the 22 SSIs identified by traditional surveillance, Rule A
      identified 19 (86.4%) and Rule B identified 13 (59.1%) cases. Positive and
      negative agreement between Rules A and B within these "positive controls" was
      81.3% and 50.0% with a kappa of 0.37 (95% CI 0.04-0.70). CONCLUSION: Differences
      in the rates of SSI identified by computer algorithms depend on sources and
      inherent biases in electronic data. Different algorithms may be appropriate,
      depending on the purpose of case identification. Further research on the
      reliability and validity of these algorithms and the impact of changes in
      reimbursement on clinician practices and electronic reporting is suggested.

PMID- 22136491
TI  - A supramolecular aggregate of four exchange-biased single-molecule magnets.
AB  - The reaction between 3-phenyl-1,5-bis(pyridin-2-yl)pentane-1,5-dione dioxime
      (pdpdH(2)) and triangular [Mn(III)(3)O(O(2)CMe)(py)(3)](ClO(4)) (1) affords
      [Mn(12)O(4)(O(2)CMe)(12)(pdpd)(6))](ClO(4))(4) (3). Complex 3 has a rectangular
      shape and consists of four [Mn(III)(3)O](7+) triangular units linked covalently
      by the dioximate ligands into a supramolecular [Mn(3)](4) tetramer. Solid-state
      dc and ac magnetic susceptibility measurements revealed that [Mn(3)](4) contains
      four Mn(3) single-molecule magnets (SMMs), each with an S = 6 ground state.
      Magnetization versus dc-field sweeps on a single crystal gave hysteresis loops
      below 1 K that exhibited exchange-biased quantum tunneling of magnetization
      steps, confirming 3 to be a supramolecular aggregate of four weakly exchange
      coupled SMM units.

PMID- 22136492
TI  - Identification of the GST-T1 and GST-M1 null genotypes using high resolution
      melting analysis.
AB  - Glutathione S-transferases, including GST-T1 and GST-M1, are known to be involved
      in the phase II detoxification pathways for xenobiotics as well as in the
      metabolism of endogenous compounds. Polymorphisms in these genes have been linked
      to an increased susceptibility to carcinogenesis and associated with risk factors
      that predispose to certain inflammatory diseases. In addition, GST-T1 and GST-M1
      null genotypes have been shown to be responsible for interindividual variations
      in the metabolism of arsenic, a known human carcinogen. To assess the specific
      GST genotypes in the Mexican population chronically exposed to arsenic, we have
      developed a multiplex High Resolution Melting PCR (HRM-PCR) analysis using a
      LightCycler480 instrument. This method is based on analysis of the PCR product
      melting curve that discriminates PCR products according to their lengths and base
      sequences. Three pairs of primers that specifically recognize GST-T1, GST-M1, and
      beta-globin, an internal control, to produce amplicons of different length were
      designed and combined with LightCycler480 High Resolution Melting Master Mix
      containing ResoLight, a completely saturating DNA dye. Data collected from
      melting curve analysis were evaluated using LightCycler480 software to determine
      specific melting temperatures of individual melting curves representing target
      genes. Using this newly developed multiplex HRM-PCR analysis, we evaluated GST-T1
      and GST-M1 genotypes in 504 DNA samples isolated from the blood of individuals
      residing in Zimapan, Lagunera, and Chihuahua regions in Mexico. We found that the
      Zimapan and Lagunera populations have similar GST-T1 and GST-M1 genotype
      frequencies which differ from those of the Chihuahua population. In addition, 14
      individuals have been identified as carriers of the double null genotype, i.e.,
      null genotypes in both GST-T1 and GST-M1 genes. Although this procedure does not
      distinguish between biallelic (+/+) and monoallelic (+/-) genotypes, it can be
      used in an automated workflow as a simple, sensitive, and time and money saving
      procedure for rapid identification of the GST-T1 and GST-M1 positive or null
      genotypes.

PMID- 22136493
TI  - Inhibitory activities of baicalin against renin and angiotensin-converting
      enzyme.
AB  - CONTEXT: Baicalin has been characterized as the active compound and quality
      control marker in Scutellaria baicalensis Georgi, traditionally used as a
      hypotensive herb. OBJECTIVES: To investigate the inhibitory activities of
      baicalin against renin and angiotensin-I converting enzyme (ACE) and their
      molecule mechanism of interactions. METHODS: The fluorescence method using renin
      substrate 1(R-2932) and the spectroscopy method by Cushman were used to determine
      renin and ACE activities, respectively. The fluorescence quench techniques were
      used to characterize their interactions. RESULTS: The results showed that
      baicalin inhibited renin activity with an IC(50) value of 120.36 uM and inhibited
      ACE activity with an IC(50) value of 2.24 mM in vitro. The fluorescence emission
      of both renin and ACE were efficiently quenched by baicalin and a complete
      quenching was achieved at a high concentration of baicalin. Furthermore, baicalin
      was more effective in quenching the fluorescence of renin (K(SV) = 60 * 10(3) M(
      1)) than ACE (K(SV) = 17.1 * 10(3) M(-1)). The quenching of fluorescence of renin
      and ACE involved static interactions, which was characterized by the formation of
      quencher-enzyme complex. The baicalin-renin complex formed through three-sites
      binding including the active site with a binding constant of 796.15 * 10(13) M(
      1), but there was only one binding site for the baicalin-ACE complex with a much
      smaller binding constant of 6.8 * 10(5) M(-1). CONCLUSION: The inhibition
      activity of baicalin against renin was a result of the formation of stable
      complex through multisites binding including the active site, which could explain
      the higher inhibitory efficiency.

PMID- 22136494
TI  - Increased number of Purkinje cell dendritic swellings in essential tremor.
AB  - BACKGROUND AND PURPOSE: Essential Tremor (ET) is among the most prevalent
      neurologic disorders. Growing clinical and neuro-imaging evidence implicates
      cerebellar dysfunction in the pathogenesis of ET and emerging postmortem studies
      have identified structural changes in the cerebellum, particularly in Purkinje
      cells. In this study we systematically quantified focal Purkinje cell dendritic
      swellings (DS) in 20 ET vs. 19 control brains. METHODS: In each brain, a standard
      parasagittal neocerebellar tissue block was harvested. DS were quantified in one
      7-MUm thick section stained with Luxol Fast Blue/Hematoxylin and Eosin (LH&E) and
      one section stained with Bielschowsky method. RESULTS: The number of DS were
      higher in cases than controls by LH&E (1.50 +/- 1.79 vs. 0.05 +/- 0.23, P =
      0.002) and Bielschowsky methods (2.70 +/- 3.10 vs. 0.37 +/- 0.50, P = 0.002). The
      number of DS was correlated with the number of torpedoes and marginally inversely
      correlated with the number of Purkinje cells. CONCLUSION: The current study
      documents and quantifies an additional structural abnormality in the ET
      cerebellum, adding to the growing list of such changes in this disease. The
      mechanisms that underlie this and other structural changes observed in ET are
      currently unknown, and they deserve additional exploration.

PMID- 22136495
TI  - Expression and functionality of type I interferon receptor in the megakaryocytic
      lineage.
AB  - BACKGROUND: Type I interferons (IFN-I) negatively regulate
      megakaryo/thrombopoiesis. However, expression of the IFN-I receptor (IFNAR) in
      the megakaryocytic lineage is poorly characterized. OBJECTIVES: To study the
      expression and functionality of IFNAR in the megakaryocytic lineage. METHODS AND
      RESULTS: Although IFNAR mRNA was found in every cell type studied, its protein
      expression showed differences between them. According to flow cytometry and
      immunofluorescence, IFNAR1 was observed in Meg-01, Dami, CD34+ cells and
      megakaryocytes, but not in proplatelets or platelets. Immunoblotting assays
      showed that IFNAR1 and IFNAR2 were highly expressed in all cell types, except in
      platelets where it was barely detectable. Regarding IFNAR1, 130- and 90-kDa bands
      were detected in Meg-01 and Dami, whereas 130- and 60-kDa bands were found in
      CD34+ cells and megakaryocytes. Activation of megakaryocytic IFNAR by IFN-beta
      induced pSTAT1/2 and upregulated the antiviral genes IRF7 and MXA. The latter
      response was completely suppressed by IFNAR blockade. In contrast, the low levels
      of IFNAR in platelets were not functional as pSTAT1/2, aggregation and P-selectin
      expression were not induced by IFN-I. In addition, megakaryocytes increased IFN-I
      transcript levels and produced IFN-beta upon stimulation with PolyI:C, a
      synthetic dsRNA that mimics viral infection. CONCLUSIONS: Early progenitors and
      mature megakaryocytes, but not platelets, express functional IFNAR and
      synthetize/release IFN-beta, revealing not only that megakaryo/thrombopoiesis
      regulation by IFN-I is associated with a specific interaction with its receptor,
      but also that megakaryocytes may play a role in the antiviral defense by being
      both IFN producers and responders.

PMID- 22136496
TI  - Why plant science matters.

PMID- 22136497
TI  - Herbs and secondary woodiness--keeping up the cambial habit.

PMID- 22136498
TI  - Terrestrial vs aquatic plants: how general is the drag tolerance-avoidance trade
      off?

PMID- 22136499
TI  - Molecular systematic perspectives on biome origins and dynamics.

PMID- 22136500
TI  - New frontiers in community and ecosystem genetics for theory, conservation, and
      management.

PMID- 22136501
TI  - Tropical forests in a warming world.

PMID- 22136502
TI  - Large band gap opening between graphene Dirac cones induced by Na adsorption onto
      an Ir superlattice.
AB  - We investigate the effects of Na adsorption on the electronic structure of bare
      and Ir cluster superlattice-covered epitaxial graphene on Ir(111) using angle
      resolved photoemission spectroscopy and scanning tunneling microscopy. At Na
      saturation coverage, a massive charge migration from sodium atoms to graphene
      raises the graphene Fermi level by ~1.4 eV relative to its neutrality point. We
      find that Na is adsorbed on top of the graphene layer, and when coadsorbed onto
      an Ir cluster superlattice, it results in the opening of a large band gap of
      Delta(Na/Ir/G) = 740 meV, comparable to the one of Ge and with preserved high
      group velocity of the charge carriers.

PMID- 22136503
TI  - Doping monolayer graphene with single atom substitutions.
AB  - Functionalized graphene has been extensively studied with the aim of tailoring
      properties for gas sensors, superconductors, supercapacitors, nanoelectronics,
      and spintronics. A bottleneck is the capability to control the carrier type and
      density by doping. We demonstrate that a two-step process is an efficient way to
      dope graphene: create vacancies by high-energy atom/ion bombardment and fill
      these vacancies with desired dopants. Different elements (Pt, Co, and In) have
      been successfully doped in the single-atom form. The high binding energy of the
      metal-vacancy complex ensures its stability and is consistent with in situ
      observation by an aberration-corrected and monochromated transmission electron
      microscope.

PMID- 22136504
TI  - Early markers of tubular dysfunction in antiretroviral-experienced HIV-infected
      patients treated with tenofovir versus abacavir.
AB  - Tenofovir disoproxil fumerate (TDF) is an effective nucleoside reverse
      transcriptase inhibitor for HIV infection but it is potentially nephrotoxic. A
      selective mithochondrial toxicity has been hypothesized. To assess early markers
      of renal toxicity, we evaluated a cohort of antiretroviral (ARV)-experienced HIV
      patients who had been switched from a thymidinic backbone to either a
      TDF/emtricitabine regimen (TDF; 73 patients) or an abacavir/lamivudine (ABV)
      regimen (28 patients). Markers of mitochondrial toxicity (cytochrome c, Cyc) or
      cytosolic (alpha-glutathione S transferase, alpha-GST) together with common
      indicators of renal damage were assessed at baseline (T0) and after 1 (T1), 3
      (T2), 6 (T3), and 12 (T4) months of patient exposure to therapy. Clinical
      features of both groups were comparable at T0. There was no significant variation
      in estimated glomerular filtration rate (eGRF), median urine protein excretion,
      or microalbuminuria and serum phosphate levels in both groups during the study
      period. There was a significant increase in urinary excretion of phosphate in
      patients on TDF compared to those on ABV at T3 and T4. Fractional excretion of
      uric acid was also altered in the two treatment groups; there was no change in
      the ABV (constantly less than 0.10), but a progressive increase in TDF patients.
      Serum potassium levels were significantly lower in ABV than in TDF treated
      patients. Urine concentrations of alpha-GST showed a nonsignificant variation in
      both groups, while Cyc excretion was significantly higher at T1 and T3 in TDF
      treated compared to ABV-treated patients. In conclusion, TDF may be associated
      with subclinical mitochondrial damage, inducing at a later stage increased
      urinary excretion of phosphate and uric acid, as markers of incipient tubular
      injury.

PMID- 22136505
TI  - Gross hematuria as the presentation of an inguinoscrotal hernia: a case report.
AB  - INTRODUCTION: Several complications have been reported with inguinal hernias.
      Although hematuria and flank pain, either as the presentation or as a
      complication of inguinal hernia, are infrequent, this condition may lead to the
      development of obstructive uropathy, which can have diverse manifestations. CASE
      PRESENTATION: A 71-year-old Iranian man with Persian ethnicity presented with new
      onset episodes of gross hematuria and left-sided flank pain. A physical
      examination revealed a large and non-tender inguinal hernia on his left side. An
      initial workup included an abdominal ultrasound, an intravenous pyelogram and
      cystoscopy, which showed left hydronephrosis and a bulging on the left-side of
      his bladder wall. On further evaluation, computed tomography confirmed that his
      sigmoid colon was the source of the pressure effect on his bladder, resulting in
      hydroureteronephrosis and hematuria. No tumoral lesion was evident. Herniorrhaphy
      led to the resolution of his signs and symptoms. CONCLUSION: Our case illustrates
      a rare presentation of inguinal hernia responsible for gross hematuria and
      unilateral hydronephrosis. Urologic signs and symptoms can be caused by the
      content of inguinal hernias. They can also present as complications of inguinal
      hernias.

PMID- 22136506
TI  - NADPH oxidase-dependent and -independent mechanisms of reported inhibitors of
      reactive oxygen generation.
AB  - NADPH oxidase isoform-2 (NOX2) generates reactive oxygen species (ROS) that
      contribute to neurodegenerative and cardiovascular pathologies. However,
      validation of NOX2 as a pharmacotherapeutic target has been hampered by a lack of
      mechanistically-defined inhibitors. Using cellular and biochemical assays, we
      explored previously reported inhibitors of ROS production (perhexiline, suramin,
      VAS2870 and two Shionogi patent compounds) as direct NOX2 inhibitors. All but
      suramin, which presumably lacks cell penetrance, inhibit cellular ROS production.
      However, only perhexiline and suramin inhibit biochemical NOX2 activity. Indeed,
      our data suggest that NOX2 inhibition by perhexiline may contribute significantly
      to its demonstrated cardioprotective effects. Inhibition of protein kinase
      CbetaII explains the cellular activity of the Shionogi compounds, whereas VAS2870
      inhibits by an as-yet unidentified mechanism unrelated to direct NOX2 function or
      subunit assembly. These data delineate the mechanisms of action of these
      compounds and highlight their strengths and limitations for use in future target
      validation studies.

PMID- 22136507
TI  - Elderly care in daily living in rural Vietnam: need and its socioeconomic
      determinants.
AB  - BACKGROUND: The proportion of older people is increasing rapidly in Vietnam. The
      majority of the elderly live in rural areas. Their health status is generally
      improving but this is less pronounced among the most vulnerable groups. The
      movement of young people for employment and the impact of other socioeconomic
      changes leave more elderly on their own and with less family support. This study
      aims to assess the daily care needs and their socioeconomic determinants among
      older people in a rural setting. METHODS: In 2007, people aged 60 years and
      older, living in 2,240 households, were randomly selected from the FilaBavi
      Demographic Surveillance System (DSS). They were interviewed using structured
      questionnaires to assess needed support in activities of daily living (ADLs).
      Individuals were interviewed about the presence of chronic illnesses that had
      been diagnosed by a physician. Participant socioeconomic characteristics were
      extracted from the FilaBavi repeat census. The repeat census used a repeat of the
      same survey methods and questions as the original FilaBavi DSS. Distributions of
      study participants by socioeconomic group, supports needed, levels of support
      received, types of caregivers, and the ADL index were described. Multivariate
      analyses were performed to identify socioeconomic determinants of the ADL index.
      RESULTS: The majority of older people do not need of support for each specific
      ADL item. Dependence in instrumental or intellectual ADLs was more common than
      for basic ADLs. People who need total help were less common than those who need
      some help in most ADLs. Over three-fifths of those who need help receive enough
      support in all ADL dimensions. Children and grandchildren are the main
      caregivers. Age group, sex, educational level, marital status, household
      membership, working status, household size, living arrangement, residential area,
      household wealth, poverty status, and chronic illnesses were determinants of
      daily care needs in old age. CONCLUSIONS: Although majority of older people who
      needed help received enough support in daily care, the need of care is more
      demanded in disadvantaged groups. Future community-based, long-term elderly care
      should focus on instrumental and intellectual ADLs among the general population
      of older people, and on basic ADLs among those with chronic illnesses.
      Socioeconomic determinants of care needs should be addressed in future
      interventions.

PMID- 22136508
TI  - Bivariate analysis of basal serum anti-Mullerian hormone measurements and human
      blastocyst development after IVF.
AB  - BACKGROUND: To report on relationships among baseline serum anti-Mullerian
      hormone (AMH) measurements, blastocyst development and other selected embryology
      parameters observed in non-donor oocyte IVF cycles. METHODS: Pre-treatment AMH
      was measured in patients undergoing IVF (n = 79) and retrospectively correlated
      to in vitro embryo development noted during culture. RESULTS: Mean (+/- SD) age
      for study patients in this study group was 36.3 +/- 4.0 (range = 28-45) yrs, and
      mean (+/- SD) terminal serum estradiol during IVF was 5929 +/- 4056 pmol/l. A
      moderate positive correlation (0.49; 95% CI 0.31 to 0.65) was noted between basal
      serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive
      correlation (0.44) was observed between serum AMH and number of early cleavage
      stage embryos (95% CI 0.24 to 0.61), suggesting a relationship between serum AMH
      and embryo development in IVF. Of note, serum AMH levels at baseline were
      significantly different for patients who did and did not undergo blastocyst
      transfer (15.6 vs. 10.9 pmol/l; p = 0.029). CONCLUSIONS: While serum AMH has
      found increasing application as a predictor of ovarian reserve for patients prior
      to IVF, its roles to estimate in vitro embryo morphology and potential to advance
      to blastocyst stage have not been extensively investigated. These data suggest
      that baseline serum AMH determinations can help forecast blastocyst developmental
      during IVF. Serum AMH measured before treatment may assist patients, clinicians
      and embryologists as scheduling of embryo transfer is outlined. Additional
      studies are needed to confirm these correlations and to better define the role of
      baseline serum AMH level in the prediction of blastocyst formation.

PMID- 22136509
TI  - Treatment of recurrent glomus tumor using Mohs surgery.

PMID- 22136510
TI  - Adverse mood symptoms with oral contraceptives.
AB  - In spite of combined oral contraceptives (COCs) having been available for more
      than 50 years, surprisingly little is known about the prevalence of truly COC
      related adverse mood symptoms and about the underlying biological mechanisms of
      proposed changes in mood and affect. Precise estimates of COC-related adverse
      mood symptoms are not available due to the lack of placebo-controlled trials. In
      prospective trials the frequency of women who report deteriorated mood or
      deteriorated emotional well-being varies between 4 and 10%, but it can be assumed
      that the causal relation in these prevalence rates is overestimated. Adverse mood
      symptoms and somatic symptoms are most pronounced during the pill-free interval
      of the treatment cycles, but whether extended COC regimens would be more
      favorable in this respect is not known. COCs with anti-androgenic progestagens,
      such as drospirenone and desogestrel, appear more favorable in terms of mood
      symptoms than progestagens with a more androgenic profile. Available data suggest
      that lower doses of ethinylestradiol could be beneficial.

PMID- 22136511
TI  - Differential response patterns on the Personality Assessment Inventory (PAI) in
      compensation-seeking and non-compensation-seeking mild traumatic brain injury
      patients.
AB  - There is relatively little research on the Personality Assessment Inventory (PAI)
      with mild traumatic brain injury (MTBI) populations. There is also little
      research on how compensation-seeking status affects personality assessment
      results in MTBI patients. The current study examined the PAI scales and subscales
      in two MTBI groups, one composed of compensation-seeking MTBI patients and the
      other consisting of non-compensation-seeking MTBI patients. Results indicated
      significant differences on several scales and subscales between the two MTBI
      groups, with the compensation-seeking MTBI patients having significantly higher
      elevations on scales related to somatic preoccupation (Somatic Complaint Scale,
      SOM), emotional distress (Anxiety Scale, ANX; Anxiety Related Disorders Scale,
      ARD; Depression Scale, DEP), and the Negative Impression Management, NIM,
      validity scale. All the SOM subscales and the Anxiety Cognitive (ANX-C) and ANX
      Affective, ANX-A, subscales were also elevated in the compensation-seeking group.
      Results indicated that several scales on the PAI were sensitive to group
      differences in compensation-seeking status in MTBI patients.

PMID- 22136512
TI  - HLA alleles and drug hypersensitivity reactions.
AB  - The human leucocyte antigen (HLA) system is well known for its association with
      certain diseases such as ankylosing spondylitis, celiac disease and many others.
      More recently, severe and even fatal drug hypersensitivity reactions linked to
      particular HLA alleles have been discovered. The significance of these
      discoveries has led the European Medicines Agency (EMA) and its member state
      agencies to recommend HLA gene testing before initiation of drug treatment. To
      date, the following drugs have been identified as causing significant drug
      hypersensitivity reactions in patients who have the following HLA alleles:
      abacavir and HLA-B*57:01, carbamazepine and HLA-B*15:02/A*31:01 and finally
      allopurinol and HLA-B*58:01. This review will outline and discuss these three
      drugs and their associated HLA alleles as well as examine the pathogenesis of the
      drug hypersensitivity reactions.

PMID- 22136513
TI  - Optical properties of a visible push-pull chromophore covalently bound to
      carbohydrates: solution and gas-phase spectroscopy combined to theoretical
      investigations.
AB  - The use of visible absorbing and fluorescent tags for sensing and structural
      analysis of carbohydrates is a promising route in a variety of medical,
      diagnostic, and therapeutic contexts. Here we report an easy method for covalent
      attachment of nonfluorescent push-pull chromophores based on the 4-cyano-5
      dicyanomethylene-2-oxo-3-pyrroline ring to carbohydrate moieties. The impact of
      sugar grafting on the optical properties of the push-pull chromophore in the gas
      phase and in solution was investigated by absorption and action spectroscopy and
      theoretical methods. The labeled sugars efficiently absorb photons in the visible
      range, as demonstrated by their intense photodissociation in a quadrupole ion
      trap. A strong blue shift (-70 nm) of the gas-phase photodissociation intensity
      maximum is observed upon sugar grafting, whereas no such effect is visible on the
      solution absorption spectra. Molecular dynamics simulations of labeled maltose in
      the gas phase describe strong interactions between the sulfonated chromophore and
      the carbohydrate, which lead to cyclic conformations. These are not observed in
      the simulations with explicit solvation. Time-dependent density functional theory
      (TD-DFT) calculations on model molecules permit us to attribute the observed
      shift to the formation of such cyclic conformations and to the displacement of
      the negative charge relative to the aromatic moiety of the chromophore.

PMID- 22136514
TI  - Adverse life event and risk of cognitive impairment: a 5-year prospective
      longitudinal study in Chongqing, China.
AB  - BACKGROUND AND PURPOSE: Current knowledge of factors that increase or decrease
      the risk of cognitive impairment in elderly people is limited. Recently adverse
      life events appeared to be associated with the increased risk of cognitive
      impairment in elderly people. However, this is less studied. We conducted a 5
      year prospective study to evaluate the association between adverse life events
      and the risk of cognitive impairment in Chinese elderly people. METHODS: Of 9167
      community residents aged 55 years and over, 5262 were enrolled into the study and
      followed up annually for 5 years. At baseline demographic data, smoking and
      drinking status, medical history, adverse life events, clinical, functional and
      cognitive status, depressive symptom, and complementary data were collected. The
      cognitive status was assessed using a structured battery of neuropsychological
      tests. Subjects were followed-up annually to assess the cognitive function during
      follow-up. RESULTS: Over the follow-up period of 5 years, cognitive impairment
      developed in 569 subjects. Among the adverse life events, the death of the spouse
      and a financial crisis were associated with the increased risk of cognitive
      impairment. These associations persisted after adjusting for the subjects with
      possible baseline pre-clinical cognitive impairment, depressive symptom, stroke
      and vascular risk factors respectively. CONCLUSIONS: Adverse life events, such as
      the death of a spouse and a financial crisis, are associated with a higher risk
      of cognitive impairment. Further in-depth longitudinal and intervention studies
      are needed to confirm the causal relationship between adverse life events and
      risk of cognitive impairment in the future.

PMID- 22136515
TI  - In vitro evaluation of cellular response induced by manufactured nanoparticles.
AB  - "Nanoparticle" is defined as the particles whose diameter in at least one
      dimension is less than 100 nm. Compared with fine-particles, nanoparticles have
      large specific surface area. There is a dramatic increase over fine-particles in
      chemical and physical activities, such as ion release, adsorption ability, and
      ROS production. These properties are important for industrial use, and many
      nanoparticles are already used in products familiar to consumers as sunscreens
      and cosmetics. However, nanoparticle properties beneficial to the industry may
      also induce biological influences, including toxic activities. Recently, many
      investigations about the toxicology of nanoparticles have been reported. In the
      evaluation of nanoparticles toxicity, in vitro studies give us important
      information, especially in terms of toxic mechanisms. In vitro studies showed
      that some nanoparticles induce oxidative stress, apoptosis, production of
      cytokines, and cell death. There are reports that cellular influences of other
      nanoparticles are small. There are also reports of different results, some with
      low and some with high influences, for the same nanoparticle. One of the causes
      of this inconsistency might be a diremption of the living body influence study
      and the characterization study. Characterization of individual nanoparticles and
      their dispersions are essential for in vitro evaluation of their biological
      effects since each nanoparticle shows unique chemical and physical properties.
      Particularly, the aggregation state and metal ion release ability of
      nanoparticles affect its cellular influences. Reports concerning the
      characterization in the in vitro toxicity assessment are increasing. For an
      accurate risk assessment of nanoparticles, in this review, we outline recent
      studies of in vitro evaluation of cellular influences induced by nanoparticles.
      Moreover, we also introduce current studies about the characterization methods of
      nanoparticles and their dispersions for toxicological evaluation.

PMID- 22136516
TI  - Differential effect of oral dehydroepiandrosterone-sulphate on metabolic syndrome
      features in pre- and postmenopausal obese women.
AB  - OBJECTIVE: To analyze the effect in obese pre- and postmenopausal women of a
      daily dose of 100 mg dehydroepiandrosterone-sulphate (DHEA-S) provided over a
      period of 3 months as replacement therapy against metabolic syndrome. CONTEXT:
      Although DHEA-S appears to be effective against certain features of metabolic
      syndrome, its usefulness against this syndrome as a whole has not been evaluated
      to date. DESIGN/PATIENTS: A randomized, double-blind placebo-controlled trial was
      conducted involving 61 postmenopausal women, who received DHEA-S (n = 41) or
      placebo (n = 20) for 3 months. The effect of DHEA-S treatment on the same
      postmenopausal women was compared with the effects observed in a group of
      premenopausal women (n = 20). MEASUREMENTS: Anthropometric measurements were
      taken at the beginning and at the end of the treatment. Similarly, different
      parameters that define metabolic syndrome and other cardiometabolic variables
      were determined. RESULTS: Dehydroepiandrosterone-sulphate replacement produced
      weight loss in the obese women studied. Moreover, waist circumference, glucose
      and systolic and diastolic blood pressure, among other metabolic syndrome
      parameters, improved in the postmenopausal group, who showed a significant
      reduction in the total metabolic syndrome score (P < 0.05). In contrast, in
      premenopausal women, the effect of DHEA-S was limited to obesity parameters, and
      no effect was observed on metabolic syndrome components. No significant changes
      were evident in the placebo group. CONCLUSIONS: An oral dose of DHEA-S is useful
      for weight loss. In obese postmenopausal women, the hormone significantly
      improves plasma biochemical levels and anthropometric characteristics, leading to
      a better metabolic profile, which highlights the usefulness of this therapy
      against metabolic syndrome in this group of women.

PMID- 22136517
TI  - Association between low colonic short-chain fatty acids and high bile acids in
      high colon cancer risk populations.
AB  - We propose that the influence of diet on colon cancer risk is mediated by the
      microbiota. To investigate how dietary fat influences risk, we compared the
      colonic contents of 12 adult high-risk African Americans (AAs) and 10 Caucasian
      Americans (CAs) who consumed a high-fat diet (123 +/- 11 g/d and 129 +/- 17 g/d,
      respectively) to 13 native Africans (NAs) who subsisted on a low-fat (38 +/- 3.0
      g/d) diet, all aged 50-60 yr. The colonic bile acids were measured by LC-MS and
      the short-chain fatty acids (SCFAs) by GC. The chief secondary colonic bile
      acids, deoxycholic acid and lithocholic acid, were correlated with fat intake and
      similar between AAs and CAs, but 3-4 times higher than in AAs (p < 0.05). The
      major SCFAs were lower in AAs (p < 0.001) and CAs (p < 0.001) compared to AAs,
      but conversely, the branched chain fatty acids (BFCA) were higher. Our results
      suggest that the higher risk of colon cancer in Americans may be partly explained
      by their high-fat and high-protein, low complex carbohydrate diet, which produces
      colonic residues that promote microbes to produce potentially carcinogenic
      secondary bile acids and less antineoplastic SCFAs. The role of BCFA in colonic
      carcinogenesis deserves further study.

PMID- 22136518
TI  - Broad substrate specificity of the amide synthase in S. hygroscopicus--new 20
      membered macrolactones derived from geldanamycin.
AB  - The amide synthase of the geldanamycin producer, Streptomyces hygroscopicus,
      shows a broader chemoselectivity than the corresponding amide synthase present in
      Actinosynnema pretiosum, the producer of the highly cytotoxic ansamycin
      antibiotics, the ansamitocins. This was demonstrated when blocked mutants of both
      strains incapable of biosynthesizing 3-amino-5-hydroxybenzoic acid (AHBA), the
      polyketide synthase starter unit of both natural products, were supplemented with
      3-amino-5-hydroxymethylbenzoic acid instead. Unlike the ansamitocin producer A.
      pretiosum, S. hygroscopicus processed this modified starter unit not only to the
      expected 19-membered macrolactams but also to ring enlarged 20-membered
      macrolactones. The former mutaproducts revealed the sequence of transformations
      catalyzed by the post-PKS tailoring enzymes in geldanamycin biosynthesis. The
      unprecedented formation of the macrolactones together with molecular modeling
      studies shed light on the mode of action of the amide synthase responsible for
      macrocyclization. Obviously, the 3-hydroxymethyl substituent shows similar
      reactivity and accessibility toward C-1 of the seco-acid as the arylamino group,
      while phenolic hydroxyl groups lack this propensity to act as nucleophiles in the
      macrocyclization. The promiscuity of the amide synthase of S. hygroscopicus was
      further demonstrated by successful feeding of four other m-hydroxymethylbenzoic
      acids, leading to formation of the expected 20-membered macrocycles. Good to
      moderate antiproliferative activities were encountered for three of the five new
      geldanamycin derivatives, which matched well with a competition assay for
      Hsp90alpha.

PMID- 22136519
TI  - Size-tunable, hexagonal plate-like Cu3P and Janus-like Cu-Cu3P nanocrystals.
AB  - We describe two synthesis approaches to colloidal Cu(3)P nanocrystals using
      trioctylphosphine (TOP) as phosphorus precursor. One approach is based on the
      homogeneous nucleation of small Cu(3)P nanocrystals with hexagonal plate-like
      morphology and with sizes that can be tuned from 5 to 50 nm depending on the
      reaction time. In the other approach, metallic Cu nanocrystals are nucleated
      first and then they are progressively phosphorized to Cu(3)P. In this case,
      intermediate Janus-like dimeric nanoparticles can be isolated, which are made of
      two domains of different materials, Cu and Cu(3)P, sharing a flat epitaxial
      interface. The Janus-like nanoparticles can be transformed back to single
      crystalline copper particles if they are annealed at high temperature under high
      vacuum conditions, which makes them an interesting source of phosphorus. The
      features of the Cu-Cu(3)P Janus-like nanoparticles are compared with those of the
      striped microstructure discovered more than two decades ago in the rapidly
      quenched Cu-Cu(3)P eutectic of the Cu-P alloy, suggesting that other
      alloy/eutectic systems that display similar behavior might give origin to
      nanostructures with flat, epitaxial interface between domains of two diverse
      materials. Finally, the electrochemical properties of the copper phosphide plates
      are studied, and they are found to be capable of undergoing
      lithiation/delithiation through a displacement reaction, while the Janus-like Cu
      Cu(3)P particles do not display an electrochemical behavior that would make them
      suitable for applications in batteries.

PMID- 22136520
TI  - Reconstruction of corneal stroma with decellularized porcine xenografts in a
      rabbit model.
AB  - PURPOSE: To evaluate the potential use of decellularized porcine stromal matrix
      (PSM) for reconstruction of corneal stroma in a rabbit model. METHODS: Ten
      chinchilla bastard rabbit corneas were exposed to a circular half-thickness
      keratotomy with a 3.0 mm diameter at the central cornea. Porcine corneas were
      decellularized using hypotonic tris buffer, ethylene diamine tetra-acetic acid
      (EDTA, 0.1%), aprotinin (10 K IU/ml) and 0.3% sodium dodecyl sulphate (SDS). The
      3.0 mm in diameter decellularized corneal stromal xenograft was inserted into the
      pocket, and the incision was closed with four 10.0 nylon sutures. Clinical
      photographs were taken at day 1, day 7, day 30 and on a monthly basis for up to 6
      months after transplantation. Six months after surgery, the rabbits were killed
      and eyes were enucleated. Haematoxylin-eosin (HE) and 4,6-diamidino-2
      phenylindole (DAPI) staining were performed to confirm the complete removal of
      the corneal cells after decellularization of porcine corneas and repopulation
      with rabbit cells. Alcian blue staining was performed for analysing the structure
      of the extracellular matrix (ECM). RESULTS: Efficient elimination of porcine
      cells was achieved by our decellularization protocol and confirmed via HE and
      DAPI stainings. Moreover, the major histoarchitectural ECM structure had been
      maintained as visualized by the alcian blue stain. Finally, the PSM was
      biocompatible with the host's epithelium evidenced as a regrowth covering the
      exposed xenograft. CONCLUSIONS: This novel technique of tissue engineering may
      provide one of many solutions to addressing anterior corneal pathological
      conditions in the face of a shortage of human corneal material.

PMID- 22136521
TI  - Oxidative stress is a consequence, not a cause, of aluminum toxicity in the
      forage legume Lotus corniculatus.
AB  - * Aluminum (Al) toxicity is a major limiting factor of crop production on acid
      soils, but the implication of oxidative stress in this process is controversial.
      A multidisciplinary approach was used here to address this question in the forage
      legume Lotus corniculatus. * Plants were treated with low Al concentrations in
      hydroponic culture, and physiological and biochemical parameters, together with
      semiquantitative metabolic and proteomic profiles, were determined. * The
      exposure of plants to 10 MUM Al inhibited root and leaf growth, but had no effect
      on the production of reactive oxygen species or lipid peroxides. By contrast,
      exposure to 20 MUM Al elicited the production of superoxide radicals, peroxide
      and malondialdehyde. In response to Al, there was a progressive replacement of
      the superoxide dismutase isoforms in the cytosol, a loss of ascorbate and
      consistent changes in amino acids, sugars and associated enzymes. * We conclude
      that oxidative stress is not a causative factor of Al toxicity. The increased
      contents in roots of two powerful Al chelators, malic and 2-isopropylmalic acids,
      together with the induction of an Al-activated malate transporter gene, strongly
      suggest that both organic acids are implicated in Al detoxification. The effects
      of Al on key proteins involved in cytoskeleton dynamics, protein turnover,
      transport, methylation reactions, redox control and stress responses underscore a
      metabolic dysfunction, which affects multiple cellular compartments, particularly
      in plants exposed to 20 MUM Al.

PMID- 22136522
TI  - Discrimination of Escherichia coli strains using glycan cantilever array sensors.
AB  - Carbohydrate-based sensors, that specifically detect sugar binding molecules or
      cells, are increasingly important in medical diagnostic and drug screening. Here
      we demonstrate that cantilever arrays functionalized with different mannosides
      allow the real-time detection of several  Escherichia coli  strains in solution.
      Cantilever deflection is thereby dependent on the bacterial strain studied and
      the glycan used as the sensing molecule. The cantilevers exhibit specific and
      reproducible deflection with a sensitivity range over four orders of magnitude.

PMID- 22136523
TI  - Antiproliferative acetogenins from a Uvaria sp. from the Madagascar dry forest.
AB  - Investigation of the endemic Madagascan plant Uvaria sp. for antiproliferative
      activity against the A2780 ovarian cancer cell line led to the isolation of two
      new acetogenins. The structures of these two compounds were elucidated on the
      basis of analysis of their 1D and 2D NMR spectra, circular dichroism, and mass
      spectrometric data, together with chemical modification. The two acetogenins
      display weak antiproliferative activity against the A2780 ovarian cancer, the
      A2058 melanoma, and the H522 lung cancer cell lines.

PMID- 22136524
TI  - Antibacterial activity of some African medicinal plants used traditionally
      against infectious diseases.
AB  - CONTEXT: Plants are known to play a crucial role in African traditional medicine
      for the treatment of infection diseases. OBJECTIVES: To investigate the claimed
      antimicrobial properties of plants traditionally used in African countries,
      providing scientific validation for their use. MATERIALS AND METHODS: Eighty
      three polar and non-polar extracts from 22 medicinal plants were screened for
      their antibacterial activity against Gram-positive (Staphylococcus aureus and
      Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas
      aeruginosa, Klebsiella pneumoniae) and Mycobacterium smegmatis using the broth
      microdilution method. RESULTS AND DISCUSSION: In vitro antibacterial activity
      against one or more tested bacteria was shown by 83% of the extracts. The highest
      activity was obtained with the methanol extracts of the aerial parts of Acacia
      karroo Hayne (Fabaceae) and Anacardium occidentale L. (Anacardiaceae) and the
      roots of Bridelia cathartica G. Bertol (Euphorbiaceae), against S. aureus
      (minimum inhibitory concentration (MIC) = 7.5 ug/mL). The same MIC values were
      exhibited against E. faecalis by the methanol extract of A. occidentale, the
      dichloromethane and methanol extracts of B. cathartica and the ethyl acetate
      extract of Momordica balsamina l. (Curcubitaceae) leaves. Gram-negative bacteria
      were less sensitive; the growth of P. aeruginosa was significantly inhibited (MIC
      = 31 ug/mL) by the n-hexane and methanol extracts of Gomphocarpus fruticosus (l.)
      Ait. (Asclepiadaceae) fruits and by the dichloromethane extract of Trichilia
      emetica Vahl (Meliaceae) seeds. Most of the active extracts were rich in
      fenols/flavonoids. CONCLUSION: This study supports the use of most of the studied
      plants in traditional medicine, for the treatment of infectious diseases. Some of
      them are worthy of further investigation.

PMID- 22136525
TI  - Identification and characterization of mutations in the promoter region of the
      factor VIII gene.

PMID- 22136526
TI  - Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to
      the periphery of the aging lung: a unifying hypothesis regarding etiology and
      pathogenesis.
AB  - CONTEXT: Idiopathic pulmonary fibrosis is a progressive, fatal lung disease
      occurring in older individuals. Despite 50 years of accrued data about the
      disease, little progress has been made in slowing functional loss or in
      decreasing patient mortality. OBJECTIVE: To present a novel hypothesis on the
      etiology and pathogenesis of idiopathic pulmonary fibrosis. DESIGN: Published
      data are reviewed regarding the epidemiology, clinical presentation, natural
      history, radiologic findings, and pathologic findings in patients with idiopathic
      pulmonary fibrosis. RESULTS: Patients with idiopathic pulmonary fibrosis may be
      predisposed genetically to tractional injury to the peripheral lung. The result
      is recurrent damage to the epithelial-mesenchymal interface, preferentially at
      the outer edges of the basilar lung lobules where tractional stress is high
      during inspiration, compliance is relatively low, and there is a greater tendency
      for alveolar collapse at end-expiration. A distinctive "reticular network of
      injury" (the fibroblast focus) forms, attended by a prolonged phase of wound
      repair (tear and slow repair). Discrete areas of alveolar collapse are observed
      in scar at the periphery of the lung lobules. The cycle repeats over many years
      resulting in progressive fibrous remodeling and replacement of the alveoli in a
      lobule by bronchiolar cysts surrounded by scar (honeycomb lung). Abnormalities in
      surfactant function are proposed as a potential mechanism of initial lung damage.
      Age of onset may be a function of a required threshold of environmental exposures
      (eg, cigarette smoking) or other comorbid injury to the aging lung. CONCLUSIONS:
      Evidence supporting this hypothesis is presented and potential mechanisms are
      discussed. A potential role for contributing cofactors is presented.

PMID- 22136527
TI  - 3-cyano-8-methyl-2-oxo-1,4-disubstituted-1,2,5,6,7,8-hexahydroquinolines:
      synthesis and biological evaluation as antimicrobial and cytotoxic agents.
AB  - The synthesis, in vitro antimicrobial and cytotoxic activities of some novel
      hexahydroquinolines supported with various pharmacophores are described. The
      results revealed that 18 compounds displayed pronounced activity against
      Staphylococcus aureus and Escherichia coli bacteria beside a moderate antifungal
      activity. Compound 25 is the most active candidate with equipotency to ampicillin
      against S. aureus, E. coli and Pseudomonas aeruginosa, together with an obvious
      antifungal activity. Additionally, 12 compounds showed remarkable cytotoxic
      efficiency against human colon carcinoma HT29, hepatocellular carcinoma Hep-G2
      and Caucasian breast adenocarcinoma MCF7 cell lines. Among these, the analogs 22
      and 25 proved to be the most active cytotoxic members. Collectively, the results
      would suggest that compounds 22 and 25 could be considered as possible dual
      antimicrobial-anticancer agents.

PMID- 22136528
TI  - Intrathecal injection of human umbilical cord blood-derived mesenchymal stem
      cells for the treatment of basilar artery dissection: a case report.
AB  - INTRODUCTION: Basilar artery dissection is a rare occurrence, and is
      significantly associated with morbidity and mortality. To the best of our
      knowledge, we report the first case of basilar artery dissection treated with
      mesenchymal stem cells. CASE PRESENTATION: We present the case of a 17-year-old
      Korean man who was diagnosed with basilar artery dissection. Infarction of the
      bilateral pons, midbrain and right superior cerebellum due to his basilar artery
      dissection was partially recanalized by intrathecal injection of human umbilical
      cord blood-derived mesenchymal stem cells. No immunosuppressants were given to
      our patient, and human leukocyte antigen alloantibodies were not detected after
      cell therapy. CONCLUSIONS: This case indicates that intrathecal injections of
      mesenchymal stem cells can be used in the treatment of basilar artery dissection.

PMID- 22136529
TI  - Breastfeeding, asthma, and allergy: a tale of two cities.
AB  - BACKGROUND: The effect of breastfeeding duration on subsequent asthma and allergy
      remains the subject of much controversy. OBJECTIVE: To investigate whether
      differences in study design or disease-related exposure modification were the
      cause of the differences in study findings. METHOD: The data from two cohorts,
      the Childhood Asthma Prevention Study (CAPS) from Australia and the Barn Allergi
      Miljo Stockholm cohort from Sweden, which had reported different findings on the
      association between breastfeeding and asthma, were combined. For this analysis,
      the definitions for breastfeeding, asthma, and allergy were harmonized. Subjects
      were included if they had at least one parent with wheeze or asthma and had a
      gestational age of more than 36 wks (combined n = 882). The risk of disease
      related exposure modification was assessed using survival analysis. RESULTS:
      Breastfeeding reduced the risk of asthma at 4/5 and 8 yrs of age in children with
      a family history of asthma. The effect was stronger in the Swedish cohort.
      Breastfeeding had no effect on the prevalence of sensitization to inhaled
      allergens in this cohort with a family history of asthma but was a risk factor
      for sensitization to cow's milk, peanuts, and eggs in the CAPS cohort at 4/5 yrs
      and in the combined cohort at 8 yrs. There was no evidence to support the
      existence of disease-related exposure modification in either cohort. CONCLUSION:
      These findings point to the importance of harmonization of features of study
      design, including subject selection criteria and variable definitions, in
      resolving epidemiological controversies such as those surrounding the impact of
      breastfeeding on asthma and allergic sensitization.

PMID- 22136531
TI  - Preventing unintentional childhood injury at home: injury circumstances and
      interventions.
AB  - New Zealand's (NZ) preschoolers carry the greatest injury burden among children
      aged 0-14 years. These injuries commonly occur at home. To identify how NZ
      addresses child injury the 1990s national injury datasets and associated free
      text were examined retrospectively, NZ injury circumstances and interventions
      were compared to internationally recognised hazards and best practice, and
      whether NZ interventions addressed common circumstances of injury was assessed.
      Certain injuries, often associated with activities of daily living, were not
      addressed by interventions, although most interventions advocated internationally
      are implemented in NZ. Possible reasons for main injuries not being addressed
      were the specificity and variable effectiveness of interventions, normality of
      many injury circumstances, difficulties in evaluating complex environments, and
      the need for active intervention. There is considerable scope for NZ to improve
      its child safety. It is unlikely that simple solutions will be found for complex
      circumstances in which injury events occur. Strategies to address multifaceted
      problems requiring changes to personal, social and societal factors are required,
      with evaluation methods able to match their complexity.

PMID- 22136530
TI  - Transmissibility and temporal changes of 2009 pH1N1 pandemic during summer and
      fall/winter waves.
AB  - BACKGROUND: In order to compare the transmissibility of the 2009 pH1N1 pandemic
      during successive waves of infections in summer and fall/winter in the Northern
      Hemisphere, and to assess the temporal changes during the course of the outbreak
      in relation to the intervention measures implemented, we analyze the
      epidemiological patterns of the epidemic in Taiwan during July 2009-March 2010.
      METHODS: We utilize the multi-phase Richards model to fit the weekly cumulative
      pH1N1 epidemiological data (numbers of confirmed cases and hospitalizations) as
      well as the daily number of classes suspended under a unique "325" partial school
      closing policy in Taiwan, in order to pinpoint the turning points of the summer
      and fall/winter waves, and to estimate the reproduction numbers R for each wave.
      RESULTS: Our analysis indicates that the summer wave had slowed down by early
      September when schools reopened for fall. However, a second fall/winter wave
      began in late September, approximately 4 weeks after the school reopened, peaking
      at about 2-3 weeks after the start of the mass immunization campaign in November.
      R is estimated to be in the range of 1.04-1.27 for the first wave, and between
      1.01-1.05 for the second wave. CONCLUSIONS: Transmissibility of the summer wave
      in Taiwan during July-early September, as measured by R, was lower than that of
      the earlier spring outbreak in North America and Europe, as well as that of the
      winter outbreak in Southern Hemisphere. Furthermore, transmissibility during
      fall/winter in Taiwan was noticeably lower than that of the summer, which is
      attributable to population-level immunity acquired from the earlier summer wave
      and also to the intervention measures that were implemented prior to and during
      the fall/winter wave.

PMID- 22136533
TI  - A rare cause of involuntary weight loss in an older woman: endometrial
      tuberculosis.

PMID- 22136532
TI  - Symmetric C-C stretching mode splitting versus CH2-chain conformation order in
      sodium montmorillonite modified by cetyltrimethylammonium bromide.
AB  - Exploiting Raman spectroscopy and computational modeling, for the first time, we
      report and explain an interesting phenomenon in clay modified by
      cetyltrimethylammonium bromide. A splitting of the CH(2)-chain's symmetric C-C
      stretching Raman mode found at ~1128 cm(-1) in cetyltrimethylammonium bromide
      into two bands at 1128 and 1139 cm(-1) in clay modified by cetyltrimethylammonium
      bromide is observed. We demonstrate that this splitting appears if two types of
      trans-segments with nonequivalent lengths and terminal groups coexist in the
      CH(2)-chain of the alkylammonium ion embedded into the clay interlayer space. We
      report Raman experimental evidence for a CH(2)-chain bending within the clay
      galleries, resulting in the symmetric C-C stretching band splitting, as was also
      suggested by computational modeling. Noteworthy, we postulate that this unique
      behavior based on CH(2)-chain bending provides a general understanding of
      conformation reorganization and switching within long CH(2)-chain molecules
      confined within modified clay interlayer galleries. For all modifier
      concentrations, we show that the intercalated cetyltrimethylammonium ions exist
      in a liquid-like state, consisting mainly of trans conformations (~86%) of two
      types in approximately equal proportions. Moreover, we demonstrate that the
      integral Raman intensity ratio I(1295)(CH(2))/I(705)(clay) provides a rapid
      nondestructive quantification of the relative content of alkylammonium ions in
      modified clays. These results demonstrate that a simple direct monitoring of
      specific modifier-dependent interlayer conformational states is possible, which
      is of great importance for a tunable fabrication of modified clays-based
      nanocomposites with desired properties.

PMID- 22136534
TI  - Transthyretin cardiac amyloidosis diagnosed by analyzing a prostatic tissue
      sample: a case report.

PMID- 22136535
TI  - Antibiotic-induced cardiac arrhythmia in elderly patients.

PMID- 22136536
TI  - Glomerular membranous nephropathy and Werner syndrome: a case report.

PMID- 22136537
TI  - Polypharmacy and underprescribing in older adults: rational underprescribing by
      general practitioners.

PMID- 22136538
TI  - Plasma homocysteine level and apathy in Alzheimer's disease.

PMID- 22136539
TI  - Cognitive reserve, homocysteine, and cognition in the Bavarian School Sisters
      Study.

PMID- 22136540
TI  - Home visits by trained undergraduate pre-health professional students: an
      extension of the principles of the patient-centered medical home.

PMID- 22136541
TI  - Piloting a renal drug alert system for prescribing to residents in long-term
      care.

PMID- 22136542
TI  - Analysis of early and late outcomes after concomitant aortic valve replacement
      and coronary artery bypass graft surgery in octogenarians: a multi-institutional
      Australian study.

PMID- 22136543
TI  - Adverse drug events in older adults: development of a predictive model.

PMID- 22136544
TI  - Age-related changes in mean corpuscular volume in adult whites and African
      Americans.

PMID- 22136545
TI  - Self-perception of oral health in older adults: an important input into public
      policy-making.

PMID- 22136546
TI  - Assessing adherence to use of hip protectors: automated monitoring is feasible.

PMID- 22136547
TI  - Fractures in people with dizziness: 5-year follow-up.

PMID- 22136548
TI  - Stool antigen test in diagnosis of Helicobacter pylori in older adults with
      dyspepsia.

PMID- 22136549
TI  - Analysis of 111 cases of hepatitis E in older adults in China: 1997-2010.

PMID- 22136550
TI  - Reducing nursing home polypharmacy using systematic medication and assessment
      review and tracking: the SMART Program.

PMID- 22136551
TI  - "Wisdom lies neither in fixity nor in change but in the dialectic between the
      two"--Octavia Paz.

PMID- 22136552
TI  - Activating the knowledge-to-action cycle for geriatric care in India.
AB  - Despite a rapidly aging population, geriatrics--the branch of medicine that
      focuses on healthcare of the elderly--is relatively new in India, with many
      practicing physicians having little knowledge of the clinical and functional
      implications of aging. Negative attitudes and limited awareness, knowledge or
      acceptance of geriatrics as a legitimate discipline contribute to inaccessible
      and poor quality care for India's old. The aim of this paper is to argue that
      knowledge translation is a potentially effective tool for engaging Indian
      healthcare providers in the delivery of high quality geriatric care. The paper
      describes India's context, including demographics, challenges and current
      policies, summarizes evidence on provider behaviour change, and integrates the
      two in order to propose an action plan for promoting improvements in geriatric
      care.

PMID- 22136553
TI  - Cat's whiskers tea (Orthosiphon stamineus) extract inhibits growth of colon tumor
      in nude mice and angiogenesis in endothelial cells via suppressing VEGFR
      phosphorylation.
AB  - Cat's whiskers (Orthosiphon stamineus) is commonly used as Java tea to treat
      kidney stones including a variety of angiogenesis-dependent diseases such as
      tumorous edema, rheumatism, diabetic blindness, and obesity. In the present
      study, antitumor potential of standardized 50% ethanol extract of O. stamineus
      leaves (EOS) was evaluated against colorectal tumor in athymic mice and
      antiangiogenic efficacy of EOS was investigated in human umbilical vein
      endothelial cells (HUVEC). EOS at 100 mg/kg caused 47.62 +/- 6.4% suppression in
      tumor growth, while at 200 mg/kg it caused 83.39 +/- 4.1% tumor regression. Tumor
      histology revealed significant reduction in extent of vascularization. Enzyme
      linked immunosorbent assay showed EOS (200 mg/kg) significantly reduced the
      vascular endothelial growth factor (VEGF) level in vitro (211 +/- 0.26 pg/ml cell
      lysate) as well as in vivo (90.9 +/- 2 pg/g tissue homogenate) when compared to
      the control (378 +/- 5 and 135.5 +/- 4 pg, respectively). However, EOS was found
      to be noncytotoxic to colon cancer and endothelial cells. In vitro, EOS
      significantly inhibited the migration and tube formation of human umbilical vein
      endothelial cells (HUVECs). EOS suppressed VEGF-induced phosphorylation of VEGF
      receptor-2 in HUVECs. High performance liquid chromatography (HPLC) analysis of
      EOS showed high rosmarinic acid contents, whereas phytochemical analysis revealed
      high protein and phenolic contents. These results demonstrated that the antitumor
      activity of EOS may be due to its VEGF-targeted antiangiogenicity.

PMID- 22136554
TI  - Factor H and CFHR1 polymorphisms associated with atypical Haemolytic Uraemic
      Syndrome (aHUS) are differently expressed in Tunisian and in Caucasian
      populations.
AB  - Several polymorphisms in the complement components factor H and CFHR1 are
      associated with higher risk to develop atypical Haemolytic Uraemic Syndrome
      (aHUS) in Caucasians. We have determined the prevalence of these polymorphisms in
      Tunisian controls by using genetic and immunological techniques. No differences
      in the frequency of the factor H risk alleles c.-331C>T, c.2089A>G or c.2881G>T
      between Tunisian and Caucasians were found. On the contrary, the analysis of
      CFHR1 polymorphism revealed a higher frequency of Tunisian individuals homozygous
      for the CFHR1*Del (deleted) allele, and of individuals presenting the CFHR1*A
      phenotype. These results suggest distinct contributions of factor H and CFHR1
      polymorphisms to aHUS in Tunisian and Caucasian populations.

PMID- 22136556
TI  - Charge retention by gold clusters on surfaces prepared using soft landing of mass
      selected ions.
AB  - Monodisperse gold clusters have been prepared on surfaces in different charge
      states through soft landing of mass-selected ions. Ligand-stabilized gold
      clusters were prepared in methanol solution by reduction of
      chloro(triphenylphosphine)gold(I) with borane tert-butylamine complex in the
      presence of 1,3-bis(diphenylphosphino)propane. Electrospray ionization was used
      to introduce the clusters into the gas phase, and mass selection was employed to
      isolate a single ionic cluster species (Au(11)L(5)(3+), L = 1,3
      bis(diphenylphosphino)propane), which was delivered to surfaces at well
      controlled kinetic energies. Using in situ time-of-flight secondary ion mass
      spectrometry (TOF-SIMS), it is demonstrated that the Au(11)L(5)(3+) cluster
      retains its 3+ charge state when soft landed onto the surface of a 1H,1H,2H,2H
      perfluorodecanethiol self-assembled monolayer (FSAM) on gold. In contrast, when
      deposited onto 16-mercaptohexadecanoic acid (COOH-SAM) and 1-dodecanethiol (HSAM)
      surfaces on gold, the clusters exhibit larger relative abundances of the 2+ and
      1+ charge states, respectively. The kinetics of charge reduction on the FSAM and
      HSAM surfaces are investigated using in situ Fourier transform ion cyclotron
      resonance (FT-ICR) SIMS. It is shown that an extremely slow interfacial charge
      reduction occurs on the FSAM surface while an almost instantaneous neutralization
      takes place on the surface of the HSAM. Our results demonstrate that the size and
      charge state of small gold clusters on surfaces, both of which exert a dramatic
      influence on their chemical and physical properties, may be tuned through soft
      landing of mass-selected ions onto carefully selected substrates.

PMID- 22136555
TI  - Dietary patterns and risk of Parkinson's disease: a case-control study in Japan.
AB  - BACKGROUND: Nearly all epidemiologic studies examining the association between
      the risk of Parkinson's disease (PD) and diet have focused on single foods and
      specific nutrients. However, epidemiologic evidence for the association of
      dietary pattern with PD, namely the measurement of overall diet by considering
      the cumulative effects of nutrients is extremely limited. We conducted a hospital
      based case-control study in Japan to examine the relationship between dietary
      patterns and the risk of PD. METHODS: Patients with PD diagnosed using the UK PD
      Society Brain Bank criteria (n = 249) and controls without neurodegenerative
      diseases (n = 368) were recruited. At the time of recruitment, dietary intake
      during the preceding 1 month was assessed using a validated, self-administered
      diet history questionnaire. Dietary patterns from 33 predefined food groups
      (energy-adjusted food g/day) were extracted by factor analysis. RESULTS: Three
      dietary patterns were identified: 'Healthy', 'Western' and 'Light meal' patterns.
      After adjustment for potential non-dietary confounding factors, the Healthy
      pattern, characterized by a high intake of vegetables, seaweed, pulses,
      mushrooms, fruits and fish, was inversely associated with the risk of PD with a
      border-line significance (P for trend = 0.06). Multivariate Odds ratio (95%
      confidence intervals) for PD in the highest quartile of the Healthy pattern was
      0.54 (0.32-0.92) compared with the lowest quartile. No associations with PD were
      detected for the other two dietary patterns. CONCLUSION: In this case-control
      study in Japan, a dietary pattern consisting of high intakes of vegetables,
      fruits and fish may be associated with a decreased risk of PD.

PMID- 22136557
TI  - Consistency of GINA criteria and childhood asthma control test on the
      determination of asthma control.
AB  - BACKGROUND: Reliable assessment of asthma control is essential for effective
      treatment. Although several methods are used to assess asthma control, it is
      still suboptimal all over the world. Childhood asthma control test (C-ACT) is a
      widely used complementary test in determining the level of asthma control in
      conjunction with GINA guidelines. OBJECTIVE: To evaluate the consistency between
      the childhood asthma control test (C-ACT) and the Global Initiative for Asthma
      (GINA) guideline-based asthma control measure in children with asthma and, if
      present, to investigate the reasons for any discrepancy. METHODS: Patients and
      their caregivers filled a C-ACT and a socioeconomic status survey before the
      physician visit. Asthma control level was also assessed according to GINA
      criteria by a pediatric allergist who was blinded to C-ACT scores. RESULTS: The
      mean age of the total 314 patients was 9.0 +/- 1.9 yr, ranging between 4.3 and
      11.8 yr, of whom 56.1% (n = 176) were men. Regarding the study group, 54.8% of
      patients were controlled according to GINA, and 51.0% of patients were controlled
      according to C-ACT (score >=20). There was inconsistency between GINA and C-ACT
      in 26.7% (84/314) of the study group when the patients were evaluated
      individually (kappa = 0.464). There was not any significant variable that could
      predict the consistency and inconsistency between these methods. CONCLUSION:
      Consistency between GINA and C-ACT is not as to be expected. Using only one
      method for determining the control level of asthma does not seem to be reliable
      and accurate.

PMID- 22136559
TI  - Resilience of Mediterranean shrubland to a severe drought episode: the role of
      seed bank and seedling emergence.
AB  - Extreme climate events, such as severe drought episodes, may induce changes in
      vegetation if they induce species-specific adult mortality and changes in the
      seedling recruitment pattern. In 2005 a severe drought occurred in Donana
      National Park (south Spain) causing extensive shrubland mortality. Over the
      following years we monitored the soil seed bank and seedling emergence via a
      gradient of canopy dieback induced by the drought episode. The canopy dieback
      corresponded to an increase in emergence of seedlings of woody species in 2007,
      probably because of the reduced competition induced by canopy loss. The soil seed
      bank of woody species sampled in 2008 was less abundant on plots with a higher
      proportion of dead vegetation, probably because of depletion of the seed bank as
      a result of the increased germination in the previous year and also as a result
      of a reduction in seed supply in these sites. Accordingly, in 2009 we detected
      reduced emergence of woody species on plots that had suffered the greatest shrub
      mortality. We failed to find any significant changes in patterns of the soil seed
      bank and seedling emergence of short-lived herbaceous species, indicating greater
      resilience in these types of species. This study highlights the resilience of
      Mediterranean shrublands to climate fluctuations at one extreme of the
      variability characteristic of these ecosystems. An increase in the frequency of
      severe drought episodes - increasingly probable under the new climate conditions 
      does have the potential, however, to induce changes in vegetation, especially in
      woody communities that need more time to replenish their seed banks.

PMID- 22136558
TI  - Bacterial isolation by lectin-modified microengines.
AB  - New template-based self-propelled gold/nickel/polyaniline/platinum
      (Au/Ni/PANI/Pt) microtubular engines, functionalized with the Concanavalin A
      (ConA) lectin bioreceptor, are shown to be extremely useful for the rapid, real
      time isolation of Escherichia coli (E. coli) bacteria from fuel-enhanced
      environmental, food, and clinical samples. These multifunctional microtube
      engines combine the selective capture of E. coli with the uptake of polymeric
      drug-carrier particles to provide an attractive motion-based theranostics
      strategy. Triggered release of the captured bacteria is demonstrated by movement
      through a low-pH glycine-based dissociation solution. The smaller size of the new
      polymer-metal microengines offers convenient, direct, and label-free optical
      visualization of the captured bacteria and discrimination against nontarget
      cells.

PMID- 22136560
TI  - Determination of lignans in edible and nonedible parts of pomegranate (Punica
      granatum L.) and products derived therefrom, particularly focusing on the
      quantitation of isolariciresinol using HPLC-DAD-ESI/MSn.
AB  - A method for the characterization and quantitation of phyto-estrogenic lignans
      from pomegranate (Punica granatum L.) fruits and fruit-derived products by HPLC
      DAD-MS(n) was developed. For this purpose, edible and nonedible parts of
      pomegranate (aril, peel, mesocarp, seed, and twigs), commercial juices, juices
      produced on pilot-plant scale, and encapsulated dietary supplements were
      analyzed. In addition to the peel, mesocarp, and twigs, lignans were detected in
      two juices obtained from entire fruits, four commercial juices, and three
      encapsulated pomegranate extracts. Isolariciresinol was the predominant lignan
      with contents of 5.0, 10.5, and 45.8 mg/kg dry matter in processed pomegranate
      mesocarp, peel, and twigs, respectively. In contrast, due to their low amounts,
      quantitation of lignans in pomegranate products was impossible. Therefore,
      contrary to previous assumptions, lignans were found to be less relevant in
      pomegranate-derived products. However, the byproduct from pomegranate processing
      may be used for lignan extraction. The method presented allows one to
      differentiate between pomegranate-derived products obtained from fruits without
      peels or by dejuicing applying low pressures, which were devoid of lignans, and
      those obtained from entire fruits applying high pressures, thus containing
      lignans. Consequently, this study helps to optimize process technology aiming at
      the recovery of preparations with well-desired compositions, which may reduce the
      risk of a wide range of diseases, such as certain types of cancer.

PMID- 22136561
TI  - Analysis of clinical data of patients with different outcomes after short-time
      insemination.
AB  - The study is to analyse the clinical data of the two groups of patients with
      different fertilisation outcomes after short-time insemination and probe into
      short-time insemination indications. A retrospective study including 558 cycles
      of short-time insemination in our centre during January 2009 to June 2010 which
      were divided into two groups by the method of fertilisation, 472 cycles by IVF
      and 86 cycles by Re-ICSI group according to fertilisation conditions to and
      compare the differences between the two groups in the indexes of average female
      age, average male age, duration of infertility, forward-moving sperm counts,
      abnormal sperm rate, proportion of primary infertility, etc. The differences
      between the two groups have statistical significance in duration of infertility,
      forward-moving sperm counts, abnormal sperm rate and proportion of primary
      infertility (5.02 +/- 3.12 versus 5.86 +/- 3.35; 83.06 +/- 78.55 versus 54.02 +/-
      61.78; 83.56 +/- 5.24% versus 86.31 +/- 5.26%; 56.87% versus 74.42%; P < 0.05).
      The discrepancy between the two groups has no statistical significance in average
      female age and average male age (P > 0.05). Duration of infertility, forward
      moving sperm counts, abnormal sperm rate and previous pregnancy history have
      great significance to predict fertilisation failure, so decisions should be made
      on the basis of the above indexes when evaluating whether a patient should
      conduct short-time insemination.

PMID- 22136562
TI  - Terrestrial plant methane production and emission.
AB  - In this minireview, we evaluate all experimental work published on the phenomenon
      of aerobic methane (CH(4) ) generation in terrestrial plants and plant. Clearly,
      despite much uncertainty and skepticism, we conclude that the phenomenon is true.
      Four stimulating factors have been observed to induce aerobic plant CH(4) 
      production, i.e. cutting injuries, increasing temperature, ultraviolet radiation
      and reactive oxygen species. Further, we analyze rates of measured emission of
      aerobically produced CH(4)  in pectin and in plant tissues from different studies
      and argue that pectin is very far from the sole contributing precursor. In
      consequence, scaling up of aerobic CH(4)  emission needs to take into
      consideration other potential sources than pectin. Due to the large uncertainties
      related to effects of stimulating factors, genotypic responses and type of
      precursors, we conclude that current attempts for upscaling aerobic CH(4)  into a
      global budget is inadequate. Thus it is too early to draw the line under the
      aerobic methane emission in plants. Future work is needed for establishing the
      relative contribution of several proven potential CH(4)  precursors in plant
      material.

PMID- 22136563
TI  - RGS2 deficiency in mice does not affect platelet thrombus formation at sites of
      vascular injury.

PMID- 22136564
TI  - Synthetic chromosome platforms in plants.
AB  - Synthetic chromosomes provide the means to stack transgenes independently of the
      remainder of the genome. Combining them with haploid breeding could provide the
      means to transfer many transgenes more easily among varieties of the same
      species. The epigenetic nature of centromere formation complicates the production
      of synthetic chromosomes. However, telomere-mediated truncation coupled with the
      introduction of site-specific recombination cassettes has been used to produce
      minichromosomes consisting of little more than a centromere. Methods that have
      been developed to modify genes in vivo could be applied to minichromosomes to
      improve their utility and to continue to increase their length and genic content.
      Synthetic chromosomes establish the means to add or subtract multiple transgenes,
      multigene complexes, or whole biochemical pathways to plants to change their
      properties for agricultural applications or to use plants as factories for the
      production of foreign proteins or metabolites.

PMID- 22136565
TI  - Seed germination and vigor.
AB  - Germination vigor is driven by the ability of the plant embryo, embedded within
      the seed, to resume its metabolic activity in a coordinated and sequential
      manner. Studies using "-omics" approaches support the finding that a main
      contributor of seed germination success is the quality of the messenger RNAs
      stored during embryo maturation on the mother plant. In addition, proteostasis
      and DNA integrity play a major role in the germination phenotype. Because of its
      pivotal role in cell metabolism and its close relationships with hormone
      signaling pathways regulating seed germination, the sulfur amino acid metabolism
      pathway represents a key biochemical determinant of the commitment of the seed to
      initiate its development toward germination. This review highlights that
      germination vigor depends on multiple biochemical and molecular variables. Their
      characterization is expected to deliver new markers of seed quality that can be
      used in breeding programs and/or in biotechnological approaches to improve crop
      yields.

PMID- 22136566
TI  - Plasmodesmata paradigm shift: regulation from without versus within.
AB  - Plant cells are surrounded by cellulosic cell walls, creating a potential
      challenge to resource sharing and information exchange between individual cells.
      To overcome this, plants have evolved channels called plasmodesmata that provide
      cytoplasmic continuity between each cell and its immediate neighbors. We first
      review plasmodesmata basics-their architecture, their origin, the types of cargo
      they transport, and their molecular components. The bulk of this review discusses
      the regulation of plasmodesmata formation and function. Historically,
      plasmodesmata research has focused intensely on uncovering regulatory or
      structural proteins that reside within or immediately adjacent to plasmodesmata.
      Recent findings, however, underscore that plasmodesmata are exquisitely sensitive
      to signals far removed from the plasmodesmal channel itself. Signals originating
      from molecules and pathways that regulate cellular homeostasis-such as reactive
      oxygen species, organelle-organelle signaling, and organelle-nucleus signaling
      lead to astonishing alterations in gene expression that affect plasmodesmata
      formation and function.

PMID- 22136567
TI  - The evolution of flavin-binding photoreceptors: an ancient chromophore serving
      trendy blue-light sensors.
AB  - Photoreceptor flavoproteins of the LOV, BLUF, and cryptochrome families are
      ubiquitous among the three domains of life and are configured as UVA/blue-light
      systems not only in plants-their original arena-but also in prokaryotes and
      microscopic algae. Here, we review these proteins' structure and function, their
      biological roles, and their evolution and impact in the living world, and
      underline their growing application in biotechnologies. We present novel
      developments such as the interplay of light and redox stimuli, emerging enzymatic
      and biological functions, lessons on evolution from picoalgae, metagenomics
      analysis, and optogenetics applications.

PMID- 22136568
TI  - Guillain-Barre syndrome presenting with sensory disturbance following a herpes
      virus infection: a case report.
AB  - INTRODUCTION: We present a case of an unusual clinical manifestation of Guillain
      Barre syndrome following a pre-existing herpes virus infection. Although there
      have been several reports describing the co-existence of herpes virus infection
      and Guillain-Barre syndrome, we undertook a more in-depth study of the cross
      reactivity between herpes viruses and recommend a follow-up study based on
      serology tests. CASE PRESENTATION: A 39-year-old healthy Caucasian man with
      Guillain-Barre syndrome presented to our facility initially with sensory
      disturbance, followed by an atypical descending pattern of clinical progression.
      On physical examination, our patient showed hot and cold temperature sensory
      disturbance under the T4 vertebrae level, symmetrically diminished muscle power
      mainly to his lower limbs, blurred vision, a loss of taste and paresis and
      diminished reflexes of his lower limbs. Serology test results for common viruses
      on hospital admission were positive for cytomegalovirus immunoglobulin M,
      cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin M, herpes
      simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin M, and
      varicella zoster virus immunoglobulin G, borderline for Epstein-Barr virus
      immunoglobulin G and negative for varicella zoster virus immunoglobulin M. At one
      month after hospital admission his test results were positive for cytomegalovirus
      immunoglobulin M, cytomegalovirus immunoglobulin G, herpes simplex virus
      immunoglobulin G, Epstein-Barr virus immunoglobulin G, varicella zoster virus
      immunoglobulin G, borderline for herpes simplex virus immunoglobulin M and
      negative for Epstein-Barr virus immunoglobulin M and varicella zoster virus
      immunoglobulin M. At his six month follow-up, tests were positive for
      cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin M, herpes
      simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin G and varicella
      zoster virus immunoglobulin G and negative for cytomegalovirus immunoglobulin M,
      Epstein-Barr virus immunoglobulin M and varicella zoster virus immunoglobulin M.
      CONCLUSIONS: The clinical manifestation of Guillain-Barre syndrome in our patient
      followed a combined herpes virus infection. The cross-reactivity between these
      human herpes viruses may have a pathogenic as well as evolutionary significance.
      Our patient showed seroconversion at an early stage of Epstein-Barr virus
      immunoglobulin M to immunoglobulin G antibodies, suggesting that Epstein-Barr
      virus might have been the cause of this syndrome. Even if this case is not the
      first of its kind to be reported, it may contribute to a better understanding of
      the disease and the cross-reaction mechanisms of herpes virus infections. This
      case report may have a broader clinical impact across more than one area of
      medicine, suggesting that cooperation between different specialties is always in
      the patient's best interest.

PMID- 22136569
TI  - Perseverations and non-verbal confabulations on the Rey-Osterrieth Complex Figure
      Test in a fronto-temporal dementia single case study.
AB  - We describe the case of a patient with late onset fronto-temporal dementia (FTD),
      who presented with typical personality changes, but also perseverative and
      confabulatory behaviors while performing the Rey-Osterrieth Complex Figure Test.
      We hypothesize that the progressive atrophy of orbitobasal, medial, and
      dorsolateral frontal cortices may give rise to both confabulations and
      perseverations in the non-verbal domain. In agreement with previous studies,
      reporting atypical profiles, this case report underlines the clinical
      heterogeneity of FTD.   Authors declare that they have no conflicts of interest.

PMID- 22136570
TI  - The epidemiology of human papillomavirus infection in HIV-positive and HIV
      negative high-risk women in Kigali, Rwanda.
AB  - BACKGROUND: The prevalence, incidence and persistence of human papillomavirus
      (HPV) types in sub-Saharan Africa are not well established. The objectives of the
      current study are to describe (predictors of) the epidemiology of HPV among high
      risk women in Kigali, Rwanda. METHODS: HIV-negative, high-risk women were seen
      quarterly for one year, and once in Year 2. HIV serostatus, clinical, and
      behavioral information were assessed at each visit, HPV types at Month 6 and Year
      2, and other sexually transmitted infections (STI) at selected visits. HPV
      prevalence was also assessed in HIV-positive, high-risk women. RESULTS:
      Prevalence of any HPV was 47.0% in HIV-negative women (median age 25 years)
      compared to 72.2% in HIV-positive women (median age 27 years; OR 2.9, 95% CI 1.9
      4.6). Among HIV-negative women, cumulative incidence of high-risk (HR)-HPV was
      28.0% and persistence 32.0% after a mean period of 16.6 and 16.9 months,
      respectively. Prior Chlamydia trachomatis and Neisseria gonorrhoeae infection,
      concurrent low-risk (LR)-HPV infection and incident HSV-2 were associated with HR
      HPV prevalence among HIV-negative women; prior C. trachomatis infection and co
      infection with LR-HPV and HPV16-related HPV types with HR-HPV acquisition. HPV16
      related types were the most prevalent and persistent. CONCLUSIONS: High HPV
      prevalence, incidence and persistence were found among high-risk women in Kigali.
      HPV52 had the highest incidence; and, together with HPV33 and HPV58, were
      strongly associated with acquisition of other HR-HPV types in HIV-negative women.

PMID- 22136572
TI  - Novel effects of macrolide antibiotics on cardiovascular diseases.
AB  - Macrolide antibiotics are broadly used for the treatment of various microbial
      infections. However, they are also known to have multiple biologic effects, such
      as alteration of inflammatory factors and matrix metalloproteinases (MMPs).
      Because of controversial results in clinical trials, the effects of macrolides on
      cardiovascular diseases are still to be elucidated. It has been reported that MMP
      activity is upregulated in various cardiovascular diseases, such as myocarditis,
      cardiac transplant rejection and myocardial infarction. However, little is known
      about the effects of macrolides on cardiovascular diseases. We have reported that
      clarithromycin suppressed the development of myocarditis, cardiac rejection and
      myocardial ischemia using animal models. In this article, we reviewed the roles
      of MMPs in cardiovascular diseases and the effects of macrolides on the
      prevention of adverse tissue remodeling.

PMID- 22136573
TI  - ANZJOG in 2011.

PMID- 22136575
TI  - Self-assembly process of peptide amphiphile worm-like micelles.
AB  - Peptide amphiphile molecules (PA) are remarkably versatile and useful as building
      blocks for construction of complex supramolecular structures in a bottom-up
      fashion. Worm-like micelles of PA have been demonstrated to have successful
      application to creation of synthetic extracellular matrix materials for tissue
      engineering and regenerative medicine. However, the pathway of the self-assembly
      process of the PA worm-like micelle has not been fully characterized or
      understood. This work analyzes the self-assembly process leading to worm-like
      micelle formation in our designed PA with small-angle neutron scattering and
      atomic force microscopy. The experimental results demonstrate the existence of
      transient spherical micelles in the early stage of the process and subsequent
      micelle chain elongation by attachment of spherical micelles to the end of
      growing cylindrical micelles to form worm-like micelles in a process mimicking
      chain-growth polymerization.

PMID- 22136576
TI  - Acremostrictin, a highly oxygenated metabolite from the marine fungus Acremonium
      strictum.
AB  - The novel natural product acremostrictin was isolated from the culture broth of
      Acremonium strictum, a marine fungus collected from a Choristida sponge off the
      coast of Korea. Structurally, acremostrictin is a tricyclic lactone of an
      unprecedented skeletal class based on combined spectroscopic and X-ray
      crystallographic analyses. The new compound exhibited weak antibacterial and
      moderate antioxidant activities.

PMID- 22136577
TI  - Fatigue in survivors of childhood acute lymphoblastic and myeloid leukemia in
      Japan.
AB  - BACKGROUND: Fatigue in cancer survivors is a serious problem in pediatric
      oncology, but reports on this issue are limited, especially in Asian countries.
      METHODS: Sixty-three patients with acute lymphoblastic leukemia and 18 patients
      with acute myeloid leukemia who attended a follow-up outpatient clinic were
      enrolled. Participants were required to be >8 years of age, in remission, and
      without any cancer treatment for at least the previous 1 year. A control group
      consisted of 243 subjects whose age and gender were matched with the patient
      group. A questionnaire consisting of 12 items was devised for fatigue
      measurement. RESULTS: Principal factor analysis identified three dimensions,
      defined as physical fatigue, decreased function, and altered mood. The mean total
      and the three fatigue dimension scores tended to be higher in the control group,
      but significant differences between the scores were seen only in the total and
      physical fatigue scores. Multiple regression analysis indicated an association of
      present older age or shorter duration after completion of treatment with total
      and physical fatigue, and an association of presence of total body irradiation
      with decreased function. CONCLUSION: Pediatric leukemia survivors in Japan
      experience equal or less fatigue compared with that of controls in different
      fatigue dimensions. Elucidation of underlying mechanisms of cancer-related
      fatigue including the differences of cultural background among different
      countries is necessary for future study of this issue.

PMID- 22136578
TI  - A comparison of two short-term intensive physical activity interventions:
      methodological considerations.
AB  - BACKGROUND: Increases in chronic illness due to sedentary lifestyles and poor
      metabolic fitness have led to numerous intervention strategies to promote
      physical activity (PA). This paper describes the methodological strategies of two
      short-term PA interventions. Outcome measures reported are PA adherence and
      compliance rates during the intervention and at 3, 6 and 12-month follow-up.
      METHODS: The 40-day interventions were: a pedometer-based walking program (n =
      251) and a group-based intensive program (n = 148). There was also an active
      control group (n = 135). Intervention subjects were prescribed PA each day and
      required to record all activity sessions (pedometer steps or energy expenditure
      from heart rate monitors). RESULTS: Compliance (>= 150 min/wk PA) was highest
      post-intervention (81.1% and 64.5% for the group and pedometer subjects,
      respectively) and then progressively decreased across the 12-month follow-up
      period (final compliance rates were 53.5% and 46.6%, respectively) although they
      remained significantly higher than pre-intervention rates (zero %). There was
      significantly higher adherence to 6 months (75.0% and 64.9%), and compliance to 3
      months (64.9% and 51.0%), for group versus pedometer subjects. The active control
      group maintained the highest adherence and compliance rates across the study.
      CONCLUSIONS: The group-based program resulted in higher adherence and compliance
      rates post-intervention although both types of interventions showed long-term
      effectiveness to increase activity patterns.

PMID- 22136579
TI  - Multiple sclerosis and cognitive dysfunction: how accurate are patients' self
      assessments?

PMID- 22136580
TI  - QSAR models for toxicity of organic substances to Daphnia magna built up by using
      the CORAL freeware.
AB  - CORAL (CORrelations And Logic, http://www.insilico.eu/coral/) is a freeware
      available on the Internet. This freeware is designed to build up quantitative
      structure - property/activity relationships. The molecular structure for CORAL
      should be represented by the simplified molecular input line entry system
      (SMILES). Optimal descriptors calculated with SMILES are a mathematical function
      of the presence or absence of SMILES elements. The essence of this approach is
      the calculation of correlation weights for each element or combination of the
      elements by the Monte Carlo method. These coefficients serve to calculate the
      descriptors correlated with the endpoint for the training set, hoping that this
      correlation will also hold for the external test set. These descriptors can be
      improved by taking into account global physicochemical situations in molecules.
      An example of the physicochemical situation is the presence of oxygen and
      nitrogen. One can calculate these situations with SMILES and represent them by
      combining 0 (absence) and 1 (presence). The involving in the modelling of
      correlation weights of aforementioned physicochemical situations gave improvement
      in accuracy of models of toxicity to Daphnia magna for test set: n(test) = 75,
      r(2) = 0.7322, r(2) (pred) = 0.7193, r(2) (m) = 0.6549 (without correlation
      weights of the physicochemical situations); and n(test) = 75, r(2) = 0.7897, r(2)
      (pred) = 0.7790, r(2) (m) = 0.6850 (with aforementioned correlation weights of
      physicochemical situations).

PMID- 22136581
TI  - Comparative effects of sesame seed lignan and flaxseed lignan in reducing the
      growth of human breast tumors (MCF-7) at high levels of circulating estrogen in
      athymic mice.
AB  - Flaxseed (FS) has a breast tumor-reducing effect, possibly because of its high
      content of secoisolariciresinol diglucoside (SDG) lignan. Sesame seed (SS) is
      rich in the lignan sesamin (SES) but is non-protective. Both lignans are
      metabolized to estrogen-like enterodiol and enterolactone. The objective of this
      study was to differentiate the effects of SDG and SES on established human
      estrogen receptor-positive breast tumors (MCF-7) in athymic mice with high serum
      estrogen to help explain the different effects of FS and SS. Mice were fed for 8
      wk the basal diet (BD, control) or BD supplemented with 1 g/kg SDG or SES. SES
      reduced palpable tumor size by 23% compared to control, whereas SDG did not
      differ from SES or control. Both treatments reduced tumor cell proliferation, but
      only SES increased apoptosis. SDG and SES reduced human epidermal growth factor
      receptor 2 and endothelial growth factor receptor expressions, but only SES
      reduced downstream pMAPK. Neither treatment affected IGF-1R, vascular endothelial
      growth factor receptor-2, Akt, pAkt, or MAPK of the growth factor signaling
      pathway. Thus, at high serum estrogen levels, SDG may not account for the tumor
      reducing effect of FS. SES was more effective than SDG in reducing breast tumor
      growth, but its effect may have been lost when consumed as a component of SS.

PMID- 22136582
TI  - Sheddable ternary nanoparticles for tumor acidity-targeted siRNA delivery.
AB  - Drug delivery systems for cancer therapy usually need to be sterically stabilized
      by a poly(ethylene glycol) (PEG) layer during blood circulation to minimize
      nonspecific interactions with serum components. However, PEGylation significantly
      reduces cellular uptake of the delivery systems after they accumulate at the
      tumor site, which markedly impairs the in vivo antitumor efficiency. Here, we
      develop a ternary small interfering RNA (siRNA) delivery system with tumor
      acidity-activated sheddable PEG layer to overcome the challenge. The sheddable
      nanoparticle is fabricated by introducing a tumor acidity-responsive PEGylated
      anionic polymer to the surface of positively charged polycation/siRNA complexes
      via electrostatic interaction. We show clear evidence that introducing the
      PEGylated anionic polymer to the surface of a nanoparticle markedly reduces its
      nonspecific interactions with protein. We further demonstrate that the
      nanoparticle is capable of deshielding the PEG layer at the slightly acidic tumor
      extracellular microenvironment to facilitate the delivery of siRNA to the tumor
      cells after accumulation at the tumor site. Accordingly, this promotes the RNA
      interfering efficiencies and enhances the inhibition of tumor growth. Such
      delivery system with the ability to deshield the PEG layer at the target tissues
      has remarkable potential in cancer therapy.

PMID- 22136583
TI  - Monitoring honeybee venom immunotherapy in children with the basophil activation
      test.
AB  - BACKGROUND: New in vitro methods are essential for developing better follow-up
      criteria for venom immunotherapy (VIT). METHODS: Thirty-one children with a
      history of honeybee venom-induced systemic anaphylaxis were included in this
      prospective, single-blinded study. The basophil CD63 activation test (BAT) was
      assessed before starting VIT, at the end of the build-up phase (day 5), 6 months
      later, and after 2-4 yr of VIT. RESULTS: Basophil CD63 activation test allowed
      identification of the culprit insect in 74% of honeybee venom-allergic children.
      In comparison, IgE reactivity was single positive in only 52% of children. Five
      days after starting VIT, BAT was highly comparable to before VIT. However, after
      6 months and further after 2-4 yr of VIT, a significant and approximately
      fourfold decrease was demonstrated in CD63 response at sub-maximal 0.1 MUg/ml
      allergen concentration, which mainly represents cellular sensitivity. No such
      differences were found at a higher 1 MUg/ml of allergen concentration. Person-to
      person analyses showed that after 2-4 yr of VIT, a marked CD63 decrease was
      evident in 85% of children. In addition, elevated basophil sensitivity measured
      before VIT was associated with the appearance of side effects observed during the
      build-up phase of VIT. CONCLUSION: Basophil CD63 allergen-specific sensitivity
      seems to be a promising tool for monitoring protective immune response in
      honeybee VIT.

PMID- 22136584
TI  - Assessment of mechanical ventilation parameters on respiratory mechanics.
AB  - Better understanding of airway mechanics is very important in order to avoid lung
      injuries for patients undergoing mechanical ventilation for treatment of
      respiratory problems in intensive-care medicine, as well as pulmonary medicine.
      Mechanical ventilation depends on several parameters, all of which affect the
      patient outcome. As there are no systematic numerical investigations of the role
      of mechanical ventilation parameters on airway mechanics, the objective of this
      study was to investigate the role of mechanical ventilation parameters on airway
      mechanics using coupled fluid-solid computational analysis. For the airway
      geometry of 3 to 5 generations considered, the simulation results showed that
      airflow velocity increased with increasing airflow rate. Airway pressure
      increased with increasing airflow rate, tidal volume and positive end-expiratory
      pressure (PEEP). Airway displacement and airway strains increased with increasing
      airflow rate, tidal volume and PEEP form mechanical ventilation. Among various
      waveforms considered, sine waveform provided the highest airflow velocity and
      airway pressure while descending waveform provided the lowest airway pressure,
      airway displacement and airway strains. These results combined with optimization
      suggest that it is possible to obtain a set of mechanical ventilation strategies
      to avoid lung injuries in patients.

PMID- 22136586
TI  - Intramolecular SN'-type aromatic substitution of benzylic carbonates at their
      para-position.
AB  - The benzylic carbonates, which connect with an active methine through an o
      phenylene tether at their meta-position, are cyclized by Pd(eta(3)-C(3)H(5))Cp-S
      Phos catalyst, yielding 3-methyl-9,10-dihydrophenanthrenes. In the catalytic
      cyclization, the internal nucleophile attacks not the ortho-carbon but the para
      carbon of the benzylic ester. The [3 + 2] cycloaddition of m-(silylmethyl)benzyl
      carbonates with alkylidene malonates was developed from the palladium-catalyzed
      intramolecular S(N)'-type aromatic substitution.

PMID- 22136585
TI  - Use of fluorogenic probes to differentiate between hydrophilic and lipophilic
      antioxidant activity in a fish cell line.
AB  - In finfish aquaculture, dietary antioxidants have been shown to improve
      indicators of general fish health and to inhibit the oxidative deterioration of
      polyunsaturated fatty acids. To facilitate the characterization of novel
      antioxidants or antioxidant mixtures, we developed assays for antioxidant
      activity in a fish cell line. We used 2',7'-dichlorodihydrofluorescein diacetate
      (H(2)DCFDA) to determine the protective effects of a panel of representative
      antioxidant compounds against the formation of reactive oxygen species (ROS)
      under conditions that promote oxidative stress, whereas protective effects
      against lipid peroxidation were measured using the thiobarbituric acid reactive
      substances (TBARS) assay and a novel implementation of 4,4-difluoro-5-(4-phenyl
      1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid (C(11)
      BODIPY(581/591)). We found that the highly hydrophilic antioxidant, sodium
      ascorbate, inhibited H(2)DCFDA oxidation but had no effect on lipid peroxidation,
      whereas the highly hydrophobic antioxidant, alpha-tocopherol, potently inhibited
      lipid peroxidation but did not prevent H(2)DCFDA oxidation. The data suggest that
      a single assay is not sufficient for estimating antioxidant activity in cultured
      fish cells.

PMID- 22136587
TI  - Non-occupational contact sensitization to epoxy resin of bisphenol A among
      general dermatology patients.
AB  - BACKGROUND: Sensitization to epoxy resins often results from occupational
      exposure in various fields of construction and industry. Non-occupational
      sensitization sources and environments have remained overlooked. OBJECTIVES: To
      analyse non-occupational and occupational contact sensitization to epoxy resin of
      bisphenol A among general dermatology patients. Special attention was paid to
      patients sensitized from non-occupational sources. PATIENTS AND METHODS: During a
      10-year period, 6042 general dermatology patients were patch tested with epoxy
      resin (bisphenol A) in the Dermatology Clinic of Turku University Hospital. The
      clinical data and the sources of occupational and non-occupational exposure to
      epoxy resin were analysed in sensitized patients. RESULTS: Epoxy resin
      sensitization was found in 59 patients. Non-occupational sensitization was found
      in 21 (35%) patients, whereas the number of occupational cases was 38 (65%). The
      most common sources of non-occupational epoxy resin sensitization were materials
      used in domestic renovation and construction projects and in boat repair.
      CONCLUSIONS: Non-occupational sensitization sources account for approximately one
      third of epoxy resin sensitization cases, and therefore represent an important
      risk among hobbies and leisure activities.

PMID- 22136588
TI  - Hemibonding of hydroxyl radical and halide anion in aqueous solution.
AB  - Molecular geometries and properties of the possible reaction products between the
      hydroxyl radical and the halide anions in aqueous solution were investigated. The
      formation of two-center three-electron bonding (hemibonding) between the hydroxyl
      radical and halide anions (Cl, Br, I) was examined by density functional theory
      (DFT) calculation with a range-separated hybrid (RSH) exchange-correlation
      functional. The long-range corrected hybrid functional (LC-omegaPBE), which have
      given quantitatively satisfactory results for odd electron systems and excited
      states, was examined by test calculations for dihalogen radical anions (X(2)(-);
      X = Cl, Br, I) and hydroxyl radical-water clusters. Equilibrium geometries with
      hemibonding between the hydroxyl radical and halide anions were located by
      including four hydrogen-bonded water molecules. Excitation energies and
      oscillator strengths of sigma-sigma* transitions calculated by the time-dependent
      DFT method showed good agreement with observed values. Calculated values of the
      free energy of reaction on the formation of hydroxyl halide radical anion from
      the hydroxyl radical and halide anion were endothermic for chloride but
      exothermic for bromide and iodide, which is consistent with experimental values
      of equilibrium constants.

PMID- 22136589
TI  - Interspecific and annual variation in pre-dispersal seed predation by a
      granivorous bird in two East Asian hackberries, Celtis biondii and Celtis
      sinensis.
AB  - Pre-dispersal seed predation by granivorous birds has potential to limit fruit
      removal and subsequent seed dispersal by legitimate avian seed dispersers in bird
      dispersed plants, especially when the birds form flocks. We monitored pre
      dispersal seed predation by the Japanese grosbeak, Eophona personata, of two bird
      dispersed hackberry species (Cannabaceae), Celtis biondii (four trees) and Celtis
      sinensis (10 trees), for 3 years (2005, 2007 and 2008) in a fragmented forest in
      temperate Japan. Throughout the 3 years, predation was more intense on C.
      biondii, which, as a consequence, lost a larger part of its fruit crop. Grosbeaks
      preferred C. biondii seeds that had a comparatively lower energy content and
      lower hardness than C. sinensis, suggesting an association between seed hardness
      and selective foraging by grosbeaks. In C. biondii, intensive predation markedly
      reduced fruit duration and strongly limited fruit removal by seed dispersers,
      especially in 2007 and 2008. In C. sinensis, seed dispersers consumed fruits
      throughout the fruiting seasons in all 3 years. In C. biondii, variation in the
      timing of grosbeak migration among years was associated with annual variation in
      this bird's effects on fruit removal. Our results demonstrate that seed predation
      by flocks of granivorous birds can dramatically disrupt seed dispersal in fleshy
      fruited plants and suggest the importance of understanding their flocking
      behaviour.

PMID- 22136590
TI  - Novel roles of cAMP/cGMP-dependent signaling in platelets.
AB  - Endothelial prostacyclin and nitric oxide potently inhibit platelet functions.
      Prostacyclin and nitric oxide actions are mediated by platelet adenylyl and
      guanylyl cyclases, which synthesize cyclic AMP (cAMP) and cyclic GMP (cGMP),
      respectively. Cyclic nucleotides stimulate cAMP-dependent protein kinase (protein
      kinase A [PKA]I and PKAII) and cGMP-dependent protein kinase (protein kinase G
      [PKG]I) to phosphorylate a broad panel of substrate proteins. Substrate
      phosphorylation results in the inactivation of small G-proteins of the Ras and
      Rho families, inhibition of the release of Ca(2+) from intracellular stores, and
      modulation of actin cytoskeleton dynamics. Thus, PKA/PKG substrates translate
      prostacyclin and nitric oxide signals into a block of platelet adhesion, granule
      release, and aggregation. cAMP and cGMP are degraded by phosphodiesterases, which
      might restrict signaling to specific subcellular compartments. An emerging
      principle of cyclic nucleotide signaling in platelets is the high degree of
      interconnection between activating and cAMP/cGMP-dependent inhibitory signaling
      pathways at all levels, including cAMP/cGMP synthesis and breakdown, and PKA/PKG
      mediated substrate phosphorylation. Furthermore, defects in cAMP/cGMP pathways
      might contribute to platelet hyperreactivity in cardiovascular disease. This
      article focuses on recent insights into the regulation of the cAMP/cGMP signaling
      network and on new targets of PKA and PKG in platelets.

PMID- 22136591
TI  - Ipsilesional 'where' with contralesional 'what' neglect.
AB  - Whereas contralesional spatial neglect is usually caused by right temporo
      parietal lesions, ipsilesional spatial neglect is induced primarily by right
      frontal lesions. This report describes a 73-year-old woman with a right inferior
      parietal lesion who on 'where' tasks (line bisection and midline pointing)
      demonstrated ipsilesional neglect, but on 'what' tests (gap vs. no-gap detection
      cancellation and clothing tape removal) demonstrated contralesional neglect. This
      'what' and 'where' directional dissociation provides evidence for independent
      'what' and 'where' attentional networks; however, the reason this parietal lesion
      causes this contralesional vs. ipsilesional spatial attentional 'what' and
      'where' dichotomy remains to be determined.

PMID- 22136592
TI  - Spontaneous progression of experimental peri-implantitis at implants with
      different surface characteristics: an experimental study in dogs.
AB  - AIM: To analyse spontaneous progression of ligature-induced peri-implantitis at
      implants with different surface characteristics. MATERIAL AND METHODS: Four
      implants with similar geometry and with two different surface characteristics
      (turned/TiUnite; Nobel Biocare AB) were placed pairwise in one side of the
      mandible in five dogs, 3 months after tooth extraction. Experimental peri
      implantitis was initiated by placement of ligatures and plaque formation. The
      ligatures were removed when about 40% of the supporting bone was lost. After 6
      months, block biopsies were obtained and prepared for histological analysis.
      RESULTS: The amount of bone loss that occurred during the plaque accumulation
      period after ligature removal was significantly larger at implants with a TiUnite
      surface than at implants with a turned surface. The histological analysis
      revealed that the vertical dimensions of the lesion and the pocket epithelium and
      the apical extension of the biofilm were significantly larger at TiUnite implants
      than at turned implants. CONCLUSION: It is suggested that the implant surface
      characteristics influence progression of peri-implantitis.

PMID- 22136593
TI  - Recent derivatives from smaller classes of fermentation-derived antibacterials.
AB  - INTRODUCTION: New antibiotics, without cross-resistance to existing agents, are
      needed to treat infections caused by increasingly resistant pathogens and to
      improve the safety and efficacy of older agents. Renewed investigations of
      several older but smaller or underexploited classes of fermentation-derived
      antibiotics have generated active new derivatives and analogs that resulted from
      medicinal chemistry programs and/or manipulations of the biosynthetic pathways of
      producing microbes. Several of these programs have now produced clinical
      candidates undergoing preclinical studies or early clinical trials. AREAS
      COVERED: This review surveys the recent patent and journal literature for
      relevant new antibacterial derivatives from about 2007 until the present. EXPERT
      OPINION: Following the regulatory approvals of daptomycin and retapamulin for
      human use, these renewed investigations of underdeveloped fermentation-derived
      classes have demonstrated the further potential to discover new clinical
      candidates. However, many other classes of natural product antibiotics still
      remain underinvestigated and are thus available for renewed examinations. This
      strategy is one means for finding new antibiotics to add to the physician's
      armamentarium for treating resistant pathogens.

PMID- 22136594
TI  - Effects of cold stimulation on the harmonic structure of the blood pressure and
      photoplethysmography waveforms.
AB  - BACKGROUND: Cold stimulation (CS) accompanied by vasoconstriction can increase
      the stiffness of the arterial system. The vascular responses during CS have been
      studied using photoplethysmography (PPG), but most have focused on time-domain
      waveform indexes. Focusing on the radial arterial blood pressure (BPW) and the
      finger PPG waveforms, we aimed to determine if harmonic index could help to
      noninvasively characterize the changes in arterial pulse transmission following
      mild CS. METHODS: Trials were measured on male healthy volunteers (n=29); mild CS
      was applied by placing a bag filled with 2000 cc of water at a temperature of 19
      21 degrees C around the right lower arm. For each experiment, we recorded a 3-min
      baseline-data sequence, applied local mild CS and recorded a 3-min effect
      sequence, and then recorded another 3-min effect sequence immediately after
      stopping CS. BPW and PPG spectra were used to calculate the amplitude proportion
      (C(n)) and phase angle (P(n)) for each harmonic (for n=1-10) from averages of all
      the pulses during the measurement period. RESULTS: Several harmonic indexes were
      prominently increased following CS, including C(4)-C(10) and P(3)-P(10) for the
      BPW and C(5)-C(10) and P(3) and P(4) for PPG waveforms. CONCLUSIONS: It was
      demonstrated that the application of mild CS significantly changes several
      harmonic-analysis indexes of the BPW and the PPG waveforms. By providing detailed
      information about the pulse transmission of each frequency component, harmonic
      analysis may improve the ability to detect arterial elastic properties induced by
      CS, other forms of external stimulation, or pathological factors. It may be
      pertinent to the development of medical devices for application in telemedicine.

PMID- 22136595
TI  - Improving the emission efficiency of MBE-grown GaN/AlN QDs by strain control.
AB  - The quantum-confined stark effect induced by polarization has significant
      effects on the optical properties of nitride heterostructures. In order to
      improve the emission efficiency of GaN/AlN quantum dots [QDs], a novel epitaxial
      structure is proposed: a partially relaxed GaN layer followed by an AlN spacer
      layer is inserted before the growth of GaN QDs. GaN/AlN QD samples with the
      proposed structure are grown by molecular beam epitaxy. The results show that by
      choosing a proper AlN spacer thickness to control the strain in GaN QDs, the
      internal quantum efficiencies have been improved from 30.7% to 66.5% and from
      5.8% to 13.5% for QDs emitting violet and green lights, respectively.

PMID- 22136596
TI  - Prenatally diagnosed submicroscopic familial aberrations at 18p11.32 without
      phenotypic effect.
AB  - BACKGROUND: Recent development of MLPA (Multiplex-Ligation-dependent Probe
      Amplification, MRC-Holland) and microarray technology allows detection of a wide
      range of new submicroscopic abnormalities. Publishing new cases and case reviews
      associated with both clinical abnormalities and a normal phenotype is of great
      value. FINDINGS/RESULTS: We report on two phenotypically normal foetuses carrying
      a maternally-inherited interstitial submicroscopic abnormality of chromosome
      18p11.32. Both abnormalities were found with the aneuploidy MLPA kit P095 during
      rapid aneuploidy detection, which was offered along with conventional
      karyotyping. Foetus 1 and its mother have a 1,7 Mb deletion and foetus 2 and its
      mother have a 1,9 Mb duplication. In both cases normal babies were born. We used
      the HumanCytoSNP-12 array of Illumina to visualize the CNVs and map the
      breakpoints. CONCLUSIONS: We suggest that a CNV at 18p11.32 (528,050-2,337,486)
      may represent a new benign euchromatic variant.

PMID- 22136597
TI  - Molecular detection of tick-borne pathogens of the family Anaplasmataceae in
      Brazilian brown brocket deer (Mazama gouazoubira, Fischer, 1814) and marsh deer
      (Blastocerus dichotomus, Illiger, 1815).
AB  - Deer are important natural reservoir hosts of Anaplasmataceae. The present study
      used nested PCR and nucleotide sequencing to evaluate the occurrence of
      Anaplasmataceae species in 23 free-living and six captive specimens of the
      cervids Mazama gouazoubira and Blastocerus dichotomus in Minas Gerais State,
      Brazil. Blood samples were tested for the presence of Ehrlichia and Anaplasma
      spp. using nPCR assays and sequencing of the msp4, msp1 and 16S rRNA genes. The
      identity of each sequence was confirmed by comparison with sequences available
      from GenBank using BLAST software. Of the animals investigated, 93.1% (27/29)
      were infected with haemoparasites including Anaplasma marginale (79.3%),
      Ehrlichia chaffeensis (3.4%), Anaplasma bovis (3.4%) and Anaplasma spp. (assigned
      to A. platys and A. phagocytophilum) (17.2%). Co-infection occurred in 20% (6/29)
      of the deer examined. Four (13.8%) were infected with A. marginale and Anaplasma
      sp., one (3.4%) was infected with A. marginale and E. chaffeensis, and one (3.4%)
      was infected with A. marginale and A. bovis. The results of the present study
      suggest that cross-protection does not occur in these deer. Immunological cross
      reaction occurs when sera are tested diagnostically because these bacteria are
      closely related taxonomically, reinforcing the importance of molecular diagnosis
      followed by nucleotide sequencing.

PMID- 22136598
TI  - Heat-killed bacillus Calmette-Guerin and Mycobacterium kansasii antigen 85B
      combined vaccination ameliorates dermatitis in a mouse model of atopic dermatitis
      by inducing regulatory T cells.
AB  - BACKGROUND: Atopic dermatitis (AD) is a recurrent inflammatory skin disease
      characterized by dominant T-helper (Th) 2 cytokine response. Bacillus Calmette
      Guerin (BCG) has been used for preventing tuberculosis, and is regarded as a
      strong Th1 cytokine inducer. Antigen (Ag) 85B is a secretory protein present in
      Mycobacterium species that induces Th1 cytokine production. OBJECTIVES: We
      investigated the effects of combined vaccination of heat-killed BCG (hkBCG) and
      Mycobacterium kansasii Ag85B in an AD mouse model. METHODS: For the AD model,
      keratin 14 promoter-derived caspase-1 overexpressing mice (KCASP1Tg) were used.
      The mice received a combination therapy of hkBCG at age 3 weeks and Ag85B twice
      weekly for 11 weeks from the 4th week; Ag85B monotherapy from the 4th week; hkBCG
      monotherapy at the 3rd week; or control saline. Areas of skin lesions, cytokine
      mRNA expression and serum interleukin (IL)-18 and immunoglobulin (Ig) E levels
      were analysed. Inducible Foxp3+  regulatory T cells (iTreg), IL-10-producing T
      cells (Tr1), and interferon (IFN)-gamma/IL-4/IL-17-producing T cells were
      evaluated in the spleen. RESULTS: Saline-treated mice and hkBCG monotherapy mice
      spontaneously developed severe dermatitis. However, combined therapy with hkBCG
      and Ag85B significantly suppressed the development of skin lesions and mast cell
      infiltrations. Elevations of the serum IgE and IL-18 levels were significantly
      suppressed with combined therapy. Mice treated with hkBCG and Ag85B had a normal
      number of iTreg in the spleen, and decreased number of both IL-4- and IL-17
      producing CD4+ T cells. The effect of Ag85B monotherapy was limited. CONCLUSIONS:
      Combined vaccination with hkBCG and Ag85B decreases AD skin lesions by inducing
      regulatory T cells, suggesting that this vaccination is a potent and novel
      therapeutic strategy for AD.

PMID- 22136599
TI  - Aberrant spikelet and panicle1, encoding a TOPLESS-related transcriptional co
      repressor, is involved in the regulation of meristem fate in rice.
AB  - Post-embryonic development depends on the activity of meristems in plants, and
      thus control of cell fate in the meristem is crucial to plant development and its
      architecture. In grasses such as rice and maize, the fate of reproductive
      meristems changes from indeterminate meristems, such as inflorescence and branch
      meristems, to determinate meristems, such as the spikelet meristem. Here we
      analyzed a recessive mutant of rice, aberrant spikelet and panicle1 (asp1), that
      showed pleiotropic phenotypes such as a disorganized branching pattern, aberrant
      spikelet morphology, and disarrangement of phyllotaxy. Close examination revealed
      that regulation of meristem fate was compromised in asp1: degeneration of the
      inflorescence meristem was delayed, transition from the branch meristem to the
      spikelet meristem was accelerated, and stem cell maintenance in both the branch
      meristem and the spikelet meristem was compromised. The genetic program was also
      disturbed in terms of spikelet development. Gene isolation revealed that ASP1
      encodes a transcriptional co-repressor that is related to TOPLESS (TPL) in
      Arabidopsis and RAMOSA ENHANCER LOCUS2 (REL2) in maize. It is likely that the
      pleiotropic defects are associated with de-repression of multiple genes related
      to meristem function in the asp1 mutant. The asp1 mutant also showed de
      repression of axillary bud growth and disturbed phyllotaxy in the vegetative
      phase, suggesting that the function of this gene is closely associated with auxin
      action. Consistent with these observations and the molecular function of
      Arabidopsis TPL, auxin signaling was also compromised in the rice asp1 mutant.
      Taken together, these results indicate that ASP1 regulates various aspects of
      developmental processes and physiological responses as a transcriptional co
      repressor in rice.

PMID- 22136600
TI  - Mapping DNA quantity into electrophoretic mobility through quantum dot
      nanotethers for high-resolution genetic and epigenetic analysis.
AB  - Newly discovered nanoparticle properties have driven the development of novel
      applications and uses. We report a new observation where the electrophoretic
      mobility of a quantum dot/DNA nanoassembly can be precisely modulated by the
      degree of surface DNA conjugation. By using streptavidin-coated quantum dots
      (QDs) as nanotethers to gather biotin-labeled DNA into electrophoretic
      nanoassemblies, the QD surface charge is modulated and transformed into
      electrophoretic mobility shifts using standard agarose gel electrophoresis.
      Typical fluorescent assays quantify based on relative intensity. However, this
      phenomenon uses a novel approach that accurately maps DNA quantity into shifts in
      relative band position. This property was applied in a QD-enabled nanoassay
      called quantum dot electrophoretic mobility shift assay (QEMSA) that enables
      accurate quantification of DNA targets down to 1.1-fold (9%) changes in quantity,
      beyond what is achievable in qPCR. In addition to these experimental findings, an
      analytical model is presented to explain this behavior. Finally, QEMSA was
      applied to both genetic and epigenetic analysis of cancer. First, it was used to
      analyze copy number variation (CNV) of the RSF1/HBXAP gene, where conventional
      approaches for CNV analysis based on comparative genomic hybridization (CGH),
      microarrays, and qPCR are unable to reliably differentiate less than 2-fold
      changes in copy number. Then, QEMSA was used for DNA methylation analysis of the
      p16/CDK2A tumor suppressor gene, where its ability to detect subtle changes in
      methylation was shown to be superior to that of qPCR.

PMID- 22136601
TI  - Transaminase in rotavirus gastroenteritis.
AB  - BACKGROUND: Children infected with rotavirus often show increased levels of
      transaminase, and symptoms are characterized by white stool, similar to biliary
      atresia. Rotavirus infections are also sporadically accompanied with convulsions,
      encephalopathy and Reye syndrome. The aim of the present study was therefore to
      investigate transaminase and interleukin (IL)-6 levels in rotavirus infection, in
      order to better understand their clinical significance. METHODS: Results of liver
      function tests, mainly the elevation of transaminase and IL-6 in rotavirus
      gastroenteritis with or without convulsions, were evaluated. RESULTS: Aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) levels were high in 23
      of 26 samples (88.5%), and in three of 26 samples (11.5%), respectively. No
      significant differences in liver function tests could be found between the groups
      with or without convulsions. Three patients whose direct bilirubin levels were
      above the upper normal limit were all classified into the group without
      convulsions. Spearman's correlation coefficient was 0.89 between increasing AST
      levels and IL-6 levels. CONCLUSION: Rotavirus infection is occasionally
      accompanied with hepatitis, but only in a mild form, and does not correlate with
      neurological complications. High levels of transaminase might reflect high IL-6.

PMID- 22136603
TI  - Synthesis and biodistribution of a new (99m) Tc-oxo complex with deoxyglucose
      dithiocarbamate for tumor imaging.
AB  - The deoxyglucose dithiocarbamate (DGDTC) was radiolabeled with (99m) Tc(V)
      glucoheptonate (GH), for the potential use as radiopharmaceuticals for tumor
      imaging. For labeling, (99m) TcO-DGDTC was prepared by ligand-exchange reaction
      with (99m) Tc-GH. The radiochemical purity of the (99m) TcO-DGDTC complex was
      over 90% by thin-layer chromatography and high-performance liquid chromatography,
      without any notable decomposition at room temperature over a period of 6 h. Its
      partition coefficient indicated that it was a hydrophilic complex. The ligand
      exchange reaction occured at neutral condition and under 100  degrees C for 15
      min to achieve high radiochemical purity. In vitro cell studies showed there was
      an increase in the uptake of (99m) TcO-DGDTC as a function of incubation time and
      the cellular uptake of (99m) TcO-DGDTC was possibly mediated by way of a d
      glucose mechanism. The biodistribution of (99m) TcO-DGDTC in mice bearing S 180
      tumor showed that the complex accumulated in the tumor with good uptake and
      excellent retention. As compared with other reported (99m) Tc radiolabeled
      glucose derivatives, (99m) TcO-DGDTC showed the highest tumor uptake and good
      tumor/muscle ratios. The tumor/muscle ratio of (99m) TcO-DGDTC uptake was higher
      than that of [(18) F] FDG uptake. Single photon emission computed tomography
      (SPECT) image studies showed there was a visible accumulation in tumor sites,
      suggesting (99m) TcO-DGDTC would be a promising candidate for tumor imaging.

PMID- 22136602
TI  - Risk factors for HIV-1 seroconversion among Taiwanese men visiting gay saunas who
      have sex with men.
AB  - BACKGROUND: Men having sex with men (MSM) accounts for 33.6% of all reported
      cases of HIV-1 infection in Taiwan. The aim of this study was to investigate the
      epidemiology of HIV-1 infection among MSM in gay saunas in Taiwan. METHODS:
      Patrons of 5 gay saunas were recruited for a weekly volunteer counseling and
      testing program from 2001 to 2005. Questionnaires were collected for a risk
      factor analysis. HIV-1 subtypes were determined using DNA sequencing and
      phylogenetic analyses. RESULTS: HIV-1 prevalence rates among MSM in gay saunas in
      2001 through 2005 were 3.4%, 5.1%, 8.9%, 8.5%, and 8.3%, respectively. In total,
      81 of 1, 093 (7.4%) MSM had HIV-1 infection. Fifty-two HIV-1 strains were
      genotyped, and all of them were subtype B. HIV-seropositive men were
      significantly younger than the seronegatives. Only 37.1% used condoms every time
      during sexual intercourse. A multivariate logistic regression analysis showed
      that the risk factors for HIV-1 were being uncircumcised (odds ratio (OR) = 2.19;
      95% confidence interval (CI), 1.08~4.45); having sexual intercourse with at least
      2 partners during each sauna visit (>= 2 vs. <= 1, OR = 1.71; 95% CI, 1.02~2.89);
      and the role played during anal intercourse (versatile vs. an exclusively
      insertive role, OR = 2.76; 95% CI, 1.42~5.36). CONCLUSIONS: Overall, 7.4%
      Taiwanese MSM participating in this study had HIV-1 subtype B infection.
      Uncircumcised, being versatile role during anal intercourse, and having sex with
      more than one person during each sauna visit were main risk factors for HIV-1
      infection.

PMID- 22136604
TI  - Dry beriberi mimicking Guillain-Barre syndrome as the first presenting sign of
      thiamine deficiency.

PMID- 22136605
TI  - Human exposure from dioxins in soil.
AB  - Dioxins are a family of chemical compounds that has received considerable
      attention, both historically and currently.  This article reviews scientific
      field studies that examine the relationship between living on soil contaminated
      with dioxins and the level of dioxins in people's serum, with an emphasis on the
      University of Michigan Dioxin Exposure Study (UMDES), the largest and most
      comprehensive study of its kind.  These studies conclude that the levels of
      dioxins in serum are most strongly correlated with age, gender, body mass index,
      weight loss, breast feeding, and smoking.  Levels of dioxins in soil are not
      significant predictors for dioxin concentrations in serum. The increase in serum
      dioxin levels that is seen with age results from historic exposure and does not
      represent ongoing exposure.  Based on the scientific field studies conducted to
      date, it appears that, in the absence of the consumption of contaminated animal
      products, there is little evidence of ongoing exposure from contaminated soil.

PMID- 22136607
TI  - Extraction of tryptophan with ionic liquids studied with molecular dynamics
      simulations.
AB  - Extraction of amino acids from aqueous solutions with ionic liquids (ILs) in
      biphasic systems is analyzed with molecular dynamics (MD) simulations. Extraction
      of tryptophan (TRP) with the imidazolium-based ILs [C(4)mim][PF(6)],
      [C(8)mim][PF(6)], and [C(8)mim][BF(4)] are considered as model cases. Solvation
      free energies of TRP are calculated with MD simulations and thermodynamic
      integration in combination with an empirical force field, whose parametrization
      is based on the liquid-phase charge distribution of the ILs. Calculated solvation
      free energies reproduce successfully all observed experimental trends according
      to the previously reported partition of TRP between water and IL phases. Water is
      present in ILs as a cosolvent, due to direct contact with the aqueous phase
      during extraction, and is found to play a major role in the extraction of TRP.
      Water improves solvation of cationic TRP by 7.8 and 5.1 kcal/mol in
      [C(4)mim][PF(6)] and [C(8)mim][PF(6)], respectively, which is in the case of
      [C(4)mim][PF(6)] sufficient to extract TRP. Extraction in [C(8)mim][PF(6)] is not
      feasible, since the hydrophobic octyl groups of the cations limit the water
      concentration in the IL. The solvation of cationic TRP is 2.4 kcal/mol less
      favorable in [C(8)mim][PF(6)] than in [C(4)mim][PF(6)]. Water improves the
      solvation of TRP in ILs mostly through dipole-dipole interactions with the polar
      backbone of TRP. Extraction is most efficient with [C(8)mim][BF(4)], where
      hydrophilic BF(4)(-) anions substantially increase the water concentration in the
      IL. Additionally, stronger direct electrostatic interactions of TRP with BF(4)(-)
      anions improve its solvation in the IL further. The solvation of cationic TRP in
      [C(8)mim][BF(4)] is 3.4 kcal/mol more favorable than in [C(8)mim][PF(6)].
      Overall, the extractive power of the ILs correlates with the water saturation
      concentration of the IL phase, which in turn is determined by the hydrophilicity
      of the constituting ions. The results of this work identify relations between the
      extraction performance of ILs and the basic chemical properties of the ions,
      which provide guidelines that could contribute to the design of improved novel
      ILs for amino acid extraction.

PMID- 22136606
TI  - Estimation of cancer incidence and mortality attributable to overweight, obesity,
      and physical inactivity in China.
AB  - The objective was to provide an evidence-based, systematic assessment of the
      burden of cancer due to overweight/obesity and physical inactivity in China. This
      study evaluated the proportion of cancers of colon, rectum, pancreas, breast
      (postmenopausal), endometrium, and kidney attributable to overweight [30 kg/m(2)
      > body mass index (BMI) >= 25 kg/m(2))/obesity (BMI >= 30 kg/m(2)) and physical
      inactivity in China in 2005. Data of prevalence of overweight/obesity and lack of
      physical activity were derived from cross-sectional surveys among representative
      samples of Chinese population, and data of relative risks on cancers were derived
      from meta-analyses or large-scale studies from China and East Asian populations.
      The attributable fractions were calculated by combining both data of prevalence
      and relative risks. In China in 2005, 0.32% of cancer deaths and 0.65% of cancer
      cases were attributable to overweight and obesity combined. Lack of physical
      activity was responsible for 0.27% of cancer deaths and 0.39% of cancer cases.
      Future projections indicate that the contribution of overweight and obesity to
      the overall cancer burden will increase in the next decades. The largest
      increased attributable fractions will be for endometrial cancer. The increase in
      attributable fractions would be greater in men and in rural populations. Although
      the current burden of cancer associated with overweight/obesity and physical
      inactivity is still relatively small in China, it is expected to increase in the
      future.

PMID- 22136608
TI  - Inadvertent exposures in children with peanut allergy.
AB  - OBJECTIVES: To determine the annual incidence, characterize the severity and
      management, and identify predictors of accidental exposure among a cohort of
      children with peanut allergy. METHODS: From 2004 to November 2009, parents of
      Canadian children with a physician-confirmed peanut allergy completed entry and
      follow-up questionnaires about accidental exposures over the preceding year.
      Logistic regression analyses were used to examine potential predictors. RESULTS:
      A total of 1411 children [61.3% boys, mean age 7.1 yr (SD, 3.9)] participated.
      When all children were included, regardless of length of observation, 266
      accidental exposures occurred over 2227 patient-years, yielding an annual
      incidence rate of 11.9% (95% CI, 10.6-13.5). When all accidental exposures
      occurring after study entry and patients providing <1 yr of observation were
      excluded, 147 exposures occurred over a period of 1175 patient-years, yielding a
      rate of 12.5% (95% CI, 10.7-14.5). Only 21% of moderate and severe reactions were
      treated with epinephrine. Age >=13 yr at study entry (OR, 2.33; 95% CI, 1.20
      4.53) and a severe previous reaction to peanut (OR, 2.04; 95% CI, 1.44-2.91) were
      associated with an increased risk of accidental exposure, and increasing disease
      duration (OR, 0.88; 95% CI, 0.83-0.92) with a decreased risk. CONCLUSION: The
      annual incidence rate of accidental exposure for children with peanut allergy is
      12.5%. Children with a recent diagnosis and adolescents are at higher risk.
      Hence, education of allergic children and their families is crucial immediately
      after diagnosis and during adolescence. As many reactions were treated
      inappropriately, healthcare professionals require better education on anaphylaxis
      management.

PMID- 22136609
TI  - Foetal phonocardiographic signal denoising based on non-negative matrix
      factorization.
AB  - Foetal phonocardiography (fPCG) is a non-invasive, cost-effective and simple
      technique for antenatal care. The fPCG signals contain vital information of
      diagnostic importance regarding the foetal health. However, the fPCG signal is
      usually contaminated by various noises and thus requires robust signal processing
      to denoise the signal. The main aim of this paper is to develop a methodology for
      removal of unwanted noise from the fPCG signal. The proposed methodology utilizes
      the non-negative matrix factorization (NMF) algorithm. The developed methodology
      is tested on both simulated and real-time fPCG signals. The performance of the
      developed methodology has been evaluated in terms of the gain in signal-to-noise
      ratio (SNR) achieved through the process of denoising. In particular, using the
      NMF algorithm, a substantial improvement in SNR of the fPCG signals in the range
      of 12-30 dB has been achieved, providing a high quality assessment of foetal well
      being.

PMID- 22136610
TI  - Substituted benzoxadiazoles as fluorogenic probes: a computational study of
      absorption and fluorescence.
AB  - General chemical strategies which provide controlled changes in the emission or
      absorption properties of biologically compatible fluorophores remain elusive. One
      strategy employed is the conversion of a fluorophore-attached alkyne (or azide)
      to a triazole through a copper-catalyzed azide-alkyne coupling (CuAAC) reaction.
      In this study, we have computationally examined a series of structurally related
      2,1,3-benzoxadiazole (benzofurazan) fluorophores and evaluated changes in their
      photophysical properties upon conversion from alkyne (or azide) to triazole
      forms. We have also determined the photophysical properties for a known set of
      benzoxadiazole compounds. The absorption and emission energies have been
      determined computationally using time-dependent density functional theory (TD
      DFT) with the Perdew, Burke, and Ernzerhof exchange-correlation density
      functional (PBE0) and the 6-31+G(d) basis set. The TD-DFT results consistently
      agreed with the experimentally determined absorption and emission wavelengths
      except for certain compounds where charge-transfer excited states occurred. In
      addition to determining the absorption and emission wavelengths, simple methods
      for predicting relative quantum yields previously derived from semiempirical
      calculations were reevaluated on the basis of the new TD-DFT results and shown to
      be deficient. These results provide a necessary framework for the design of new
      substituted benzoxadiazole fluorophores.

PMID- 22136611
TI  - Development and validation of an indirect competitive enzyme-linked immunosorbent
      assay for the screening of tylosin and tilmicosin in muscle, liver, milk, honey
      and eggs.
AB  - Incorrect use of tylosin and tilmicosin could result in allergy and select
      resistance. To monitor the illegal use of these antibiotics in animals, a
      monoclonal-based indirect competitive enzyme-linked immunosorbent assay (ic
      ELISA) has been established. Several haptens were synthesized and conjugated to
      carrier protein. Female Balb/c mice were inoculated with the four different
      conjugates to produce monoclonal antibodies according to the schemes of
      immunization. Aftercell fusion and culture several times, nine hybridoma cell
      lines were isolated. Only one, 3C4 that has isotype IgG2a, was selected for
      detailed study. The cross-reactivity of the monoclonal antibody 3C4 to tylosin
      and tilmicosin was 100% and 51% respectively. The standard curves based on the
      tylosin and tilmicosin matrix calibration ranged from 2.5 to 40 MUg L(-1), with
      an IC(50) value of 6.1 MUg L(-1) and 12.1 MUg L(-1), respectively. The limits of
      detection of the ic-ELISA ranged from 5.1 MUg kg(-1) to 13.8 MUg kg(-1) in edible
      animal tissues. The recoveries were 74.1% to 120.7% with less than 18.6% of the
      coefficient of variation when tylosin and tilmicosin were spiked in various
      biological matrices with the concentrations of 25.0-200.0 MUg kg(-1). Good
      correlations between the results of the ic-ELISA and high performance liquid
      chromatography were observed in the incurred tissues. These results suggest that
      the ic-ELISA is a sensitive, accurate and low-cost method that would be a useful
      tool for the screening of the residues of tylosin and tilmicosin in muscle,
      liver, milk, honey and eggs.

PMID- 22136612
TI  - Pharmacokinetics and preliminary safety evaluation of azithromycin in adult
      horses.
AB  - Azithromycin is widely used in foals but has not been studied in adult horses.
      The goals of this study were to determine the pharmacokinetic profile and to make
      a preliminary assessment of the safety of azithromycin in adult horses.
      Azithromycin was administered intravenously (5 mg/kg) and intragastrically (10
      mg/kg) to six healthy mares in a crossover design. Serial plasma samples, blood
      neutrophils, and pulmonary macrophages were collected for the measurement of
      azithromycin concentrations. Azithromycin was also administered orally (10 mg/kg)
      once a day for 5 days to five healthy mares for preliminary evaluation of safety
      in adult horses. The bioavailability of azithromycin following intragastric
      administration was 45 +/- 12%. Concentrations within peripheral neutrophils and
      bronchoalveolar macrophages were several fold higher than that of plasma. Mild
      decreases in appetite (n = 3) and alterations in fecal consistency (n = 3) were
      noted following repeated oral administration. The pharmacokinetic profiles of
      azithromycin in adult horses, especially the slow elimination rate and
      intraneutrophil and intrapulmonary macrophage accumulation, demonstrate that it
      is conducive to use in this age group. Because of the gastrointestinal
      alterations noted, further studies are warranted before azithromycin can be
      recommended for use in adult horses.

PMID- 22136613
TI  - A mutation in the beta3 cytoplasmic tail causes variant Glanzmann thrombasthenia
      by abrogating transition of alphaIIb beta3 to an active state.
AB  - BACKGROUND: The cytoplasmic tails of alpha(IIb) and beta(3) regulate essential
      alpha(IIb) beta(3) functions. We previously described a variant Glanzmann
      thrombasthenia mutation in the beta(3) cytoplasmic tail, IVS14: -3C>G, which
      causes a frameshift with an extension of beta(3) by 40 residues. OBJECTIVES: The
      aim of this study was to characterize the mechanism by which the mutation
      abrogates transition of alpha(IIb) beta(3) from a resting state to an active
      state. METHODS:  We expressed the natural mutation, termed 742ins, and three
      artificial mutations in baby hamster kidney (BHK) cells along with wild-type (WT)
      alpha(IIb) as follows: beta(3) -742stop, a truncated mutant to evaluate the
      effect of deleted residues; beta(3) -749stop, a truncated mutant that preserves
      the NPLY conserved sequence; and beta(3) -749ins, in which the aberrant tail
      begins after the conserved sequence. Flow cytometry was used to determine ligand
      binding to BHK cells. RESULTS AND CONCLUSIONS: Surface expression of alpha(IIb)
      beta(3) of all four mutants was at least 60% of WT expression, but there was
      almost no binding of soluble fibrinogen following activation with activating
      antibodies (anti-ligand-induced-binding-site 6 [antiLIBS6] or PT25-2). Activation
      of the alpha(IIb) beta(3) mutants was only achieved when both PT25-2 and
      antiLIBS6 were used together or following treatment with dithiothreitol. These
      data suggest that the ectodomain of the four mutants is tightly locked in a
      resting conformation but can be forced to become active by strong stimuli. These
      data and those of others indicate that the middle part of the beta(3) tail is
      important for maintaining alpha(IIb) beta(3) in a resting conformation.

PMID- 22136614
TI  - Verification of the influence of the arrangement of implants on the load
      distribution (a well-known figure by Rangert).
AB  - The purpose of this study is to evaluate the effects of the number and the
      placement of implants on load distribution for multiple implants with three
      dimensional geometric analysis, and to verify the well-known conceptual figure by
      Rangert. Three teeth missing in left mandibular region was geometrically modelled
      in clinically simulated situation. Two implants placement as 'control',
      'cantilever', 'three-implants' and 'offset placements' were analyzed with
      geometric analysis. The cantilever received 180-182% load of control, that is,
      almost same to the result by Rangert (200%). Three implants received 59-65% load
      of control, that is, almost same to the result by Rangert (67%). Offset
      arrangement received 59-65% load of control, that is, larger than the result by
      Rangert (40%). It was concluded that the influence of the arrangement of implants
      on the load distribution presented in the conceptual figure by (Rangert BR,
      Sullivan RM & Jemt TM, J Oral Maxillofac Implants. 1997;12:360) was verified
      except for the effects of the offset arrangement.

PMID- 22136615
TI  - LH-RH agonists modulate amygdala response to visual sexual stimulation: a single
      case fMRI study in pedophilia.
AB  - Pedophilia is characterized by a persistent sexual attraction to prepubescent
      children. Treatment with anti-androgen agents, such as luteinizing hormone
      releasing hormone (LH-RH) agonists, reduces testosterone levels and thereby
      sexual drive and arousal. We used functional magnetic resonance imaging (fMRI) to
      compare visual erotic stimulation pre- and on-treatment with the LH-RH agonist
      leuprolide acetate in the case of homosexual pedophilia. The pre-treatment
      contrasts of the erotic pictures against the respective neutral pictures showed
      an activation of the right amygdala and adjacent parahippocampal gyrus that
      decreased significantly under treatment with leuprolide acetate. Our single case
      fMRI study supports the notion that anti-androgens may modify amygdala response
      to visual erotic stimulation, a hypothesis that should be further examined in
      larger studies.

PMID- 22136616
TI  - Posttranslational modification of cysteine in redox signaling and oxidative
      stress: Focus on s-glutathionylation.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have become
      recognized as second messengers for initiating and/or regulating vital cellular
      signaling pathways, and they are known also as deleterious mediators of cellular
      stress and cell death. ROS and RNS, and their cross products like peroxynitrite,
      react primarily with cysteine residues whose oxidative modification leads to
      functional alterations in the proteins. In this Forum, the collection of six
      review articles presents a perspective on the broad biological impact of cysteine
      modifications in health and disease from the molecular to the cellular and
      organismal levels, focusing in particular on reversible protein-S
      glutathionylation and its central role in transducing redox signals as well as
      protecting proteins from irreversible cysteine oxidation. The Forum review
      articles consider the role of S-glutationylation in regulation of the
      peroxiredoxin enzymes, the special redox environment of the mitochondria, redox
      regulation pertinent to the function of the cardiovascular system, mechanisms of
      redox-activated apoptosis in the pulmonary system, and the role of
      glutathionylation in the initiation, propagation, and treatment of
      neurodegenerative diseases. Several common themes emerge from these reviews;
      notably, the probability of crosstalk between signaling/regulation mechanisms
      involving protein-S-nitrosylation and protein-S-glutathionylation, and the need
      for quantitative analysis of the relationship between specific cysteine
      modifications and corresponding functional changes in various cellular contexts.

PMID- 22136617
TI  - Impact of PGPR inoculation on growth and antioxidant status of wheat under saline
      conditions.
AB  - Two plant growth-promoting rhizobacterial (PGPR) strains, Bacillus subtilis SU47
      and Arthrobacter sp. SU18, were found to tolerate 8% NaCl. Wheat co-inoculated
      with these two PGPR strains, and grown under different salinity regimes (2-6 dS
      m(-1) ), showed an increase in dry biomass, total soluble sugars and proline
      content. Wheat sodium content was reduced under co-inoculated conditions but not
      after single inoculation with either strain or in the control. The activity of
      antioxidant enzymes in wheat leaves decreased under salinity stress after PGPR co
      inoculation, suggesting these PGPR species could be used for amelioration of
      stress in wheat plants. Activity of three antioxidant enzymes in wheat grown with
      both PGPR strains was reduced, most notably that of catalase activity at a
      salinity of 6 dS m(-1) , when compared with the control. The results indicate
      that co-inoculation with B. subtilis and Arthrobacter sp. could alleviate the
      adverse effects of soil salinity on wheat growth.

PMID- 22136618
TI  - Relationships of osteoprotegerin with albuminuria and asymmetric dimethylarginine
      in essential hypertension: integrating vascular dysfunction.
AB  - OBJECTIVES: To investigate the inter-relationships of osteoprotegerin (OPG) with
      albumin to creatinine ratio (ACR) and asymmetric dimethylargine (ADMA) in
      hypertensive patients. METHODS: In 198 untreated non-diabetic hypertensive
      patients [130 males, mean age=51.5 years, office blood pressure (BP)=152/98 mmHg]
      ACR values and OPG and ADMA levels were determined. RESULTS: Based on the median
      value of OPG distribution (5.03 pmol/l) patients with high (n=101) compared with
      those with low OPG values (n=97) had greater 24-h systolic BP (152+/-5 versus
      137+/-7 mmHg, p<0.0001), ACR [25.3 (5-190) versus 17.3 (5-92) mg/g, p=0.003) and
      ADMA [0.62 (0.58-0.68) versus 0.57 (0.48-0.62) MUmol/l, p=0.001), independently
      of confounding factors. Multiple regression analyses revealed that ADMA (b=0.388,
      p<0.0001), 24-h systolic BP (b=0.228, p=0.01) and ACR (b=0.470, p<0.0001) were
      independent predictors of OPG (R2=0.398, p<0.0001). CONCLUSIONS: In hypertensive
      patients, high OPG levels are accompanied by pronounced albuminuria and
      endothelial dysfunction, as reflected by raised ADMA levels. Furthermore, the
      independent associations of OPG with ACR and ADMA, suggests a link between OPG
      and the progression of diffuse hypertensive vascular damage.

PMID- 22136619
TI  - Soluble peptidyl phosphoranes for metal-free, stereoselective ligations in
      organic and aqueous solution.
AB  - Protocols for solid-phase syntheses of soluble peptidyl phosphoranes are
      presented. Various supported phosphoranylidene acetates were prepared on Rink
      amide or via alkylation of trialkyl- and triarylphosphines with bromoacetyl Wang
      ester. C-Acylation was conducted racemization-free with activated Fmoc-amino
      acids, followed by SPPS (solid-phase peptide synthesis). Acidic conditions
      released decarboxylated peptidyl phosphoranes into solution. The protocol allowed
      for the electronic variation of peptidyl phosphoranes which were investigated in
      ligation reactions with azides in organic and aqueous solvents.

PMID- 22136621
TI  - The polymer/colloid duality of microgel suspensions.
AB  - Colloidal dispersions have been studied for decades as a result of their utility
      in numerous applications and as models for molecular and atomic condensed phases.
      More recently, a number of groups have exploited in such studies submicrometer
      sized hydrogel particles (microgels) that have environmentally tunable sizes. The
      experimental convenience of tuning the dispersion's colloidal volume fraction
      while maintaining a constant number density of particles provides a clear
      advantage over more tedious studies that employ traditional hard-sphere
      particles. However, as studies delved deeper into the fundamental physics of
      colloidal dispersions comprising microgel particles, it became abundantly clear
      that a microgel's utility as a tunable hard sphere was limited and that the
      impact of softness was more profound than previously appreciated. Herein we
      review the brief history of microgel-based colloidal dispersions and discuss
      their transition from tunable hard spheres to a class of soft matter that has
      revealed a landscape of physics and chemistry notable for its extraordinary
      richness and diversity.

PMID- 22136622
TI  - Optical characterisation of silicon nanocrystals embedded in SiO2/Si3N4 hybrid
      matrix for third generation photovoltaics.
AB  - Silicon nanocrystals with an average size of approximately 4 nm dispersed in
      SiO2/Si3N4 hybrid matrix have been synthesised by magnetron sputtering followed
      by a high-temperature anneal. To gain understanding of the photon absorption and
      emission mechanisms of this material, several samples are characterised optically
      via spectroscopy and photoluminescence measurements. The values of optical band
      gap are extracted from interference-minimised absorption and luminescence
      spectra. Measurement results suggest that these nanocrystals exhibit transitions
      of both direct and indirect types. Possible mechanisms of absorption and emission
      as well as an estimation of exciton binding energy are also discussed.

PMID- 22136623
TI  - H3K36 methylation is critical for brassinosteroid-regulated plant growth and
      development in rice.
AB  - Methylation of histone lysine residues plays an essential role in epigenetic
      regulation of gene expression in eukaryotes. Enzymes involved in establishment of
      the repressive H3K9 and H3K27 methylation marks have been previously
      characterized, but the deposition and function of H3K4 and H3K36 methylation
      remain uncharacterized in rice. Here, we report that rice SDG725 encodes a H3K36
      methyltransferase, and its down-regulation causes wide-ranging defects, including
      dwarfism, shortened internodes, erect leaves and small seeds. These defects
      resemble the phenotypes previously described for some brassinosteroid-knockdown
      mutants. Consistently, transcriptome analyses revealed that SDG725 depletion
      results in down-regulation by more than two-fold of over 1000 genes, including
      D11, BRI1 and BU1, which are known to be involved in brassinosteroid biosynthesis
      or signaling pathways. Chromatin immunoprecipitation analyses showed that levels
      of H3K36me2/3 are reduced in chromatin at some regions of these brassinosteroid
      related genes in SDG725 knockdown plants, and that SDG725 protein is able to
      directly bind to these target genes. Taken together, our data indicate that
      SDG725-mediated H3K36 methylation modulates brassinosteroid-related gene
      expression, playing an important role in rice plant growth and development.

PMID- 22136620
TI  - Membrane protein structure and dynamics from NMR spectroscopy.
AB  - We review the current state of membrane protein structure determination using
      solid-state nuclear magnetic resonance (NMR) spectroscopy. Multidimensional magic
      angle-spinning correlation NMR combined with oriented-sample experiments has made
      it possible to measure a full panel of structural constraints of membrane
      proteins directly in lipid bilayers. These constraints include torsion angles,
      interatomic distances, oligomeric structure, protein dynamics, ligand structure
      and dynamics, and protein orientation and depth of insertion in the lipid
      bilayer. Using solid-state NMR, researchers have studied potassium channels,
      proton channels, Ca(2+) pumps, G protein-coupled receptors, bacterial outer
      membrane proteins, and viral fusion proteins to elucidate their mechanisms of
      action. Many of these membrane proteins have also been investigated in detergent
      micelles using solution NMR. Comparison of the solid-state and solution NMR
      structures provides important insights into the effects of the solubilizing
      environment on membrane protein structure and dynamics.

PMID- 22136624
TI  - A novel pharmacophore model to identify leads for simultaneous inhibition of anti
      coagulation and anti-inflammatory activities of snake venom phospholipase A(2).
AB  - In addition to catalytic action, snake venom phospholipase A(2)  induces several
      pharmacological effects including neurotoxicity, cardiotoxicity as well as anti
      coagulant and anti-platelet aggregation effects. Therefore, strategy to identify
      dual inhibitor for this enzyme will be of much importance in medical research. In
      this paper, structure-based pharmacophore mapping, molecular docking, protein
      ligand interaction fingerprints, binding energy calculations, and binding
      affinity predictions were employed in a virtual screening strategy to identify
      new hits for dual inhibition of anti-coagulation and inflammation of
      phospholipase A(2) . A structure-based pharmacophore map was modeled which
      comprised of important interactions as observed in co-crystal of phospholipase
      A(2)  and its dual inhibitor indomethacin. The generated model was used to
      retrieve molecules from ChemBridge, a free database of commercially available
      compounds. A total of 381 molecules mapped on the developed pharmacophore model
      from ChemBridge database. The hits retrieved were further screened by molecular
      docking, protein-ligand interaction fingerprints, binding energy calculations,
      and binding affinity predictions using Genetic Optimization for Ligand Docking
      and moe. Based on these results, 32 chemo-types molecules were predicted as
      potential lead scaffolds for developing novel, potent and structurally diverse
      dual inhibitor of phospholipase A(2.).

PMID- 22136625
TI  - Monitoring emerging diseases of fish and shellfish using electronic sources.
AB  - New and emerging fish and shellfish diseases represent an important constraint to
      the growth and sustainability of many aquaculture sectors and have also caused
      substantial economic and environmental impacts in wild stocks. This paper details
      the results of 8 years of a monitoring programme for emerging aquatic animal
      diseases reported around the world. The objectives were to track global
      occurrences and, more specifically, to identify and provide advanced warning of
      disease threats that may affect wild and farmed fish stocks in the UK. A range of
      electronic information sources, including Internet newsletters, alerting services
      and news agency releases, was systematically searched for reports of new
      diseases, new presentations of known pathogens and known diseases occurring in
      new geographic locations or new host species. A database was established to log
      the details of key findings, and 250 emerging disease events in 52 countries were
      recorded during the period of study. These included 14 new diseases and a further
      16 known diseases in new species. Viruses and parasites accounted for the
      majority of reports (55% and 24%, respectively), and known diseases occurring in
      new locations were the most important emerging disease category (in which viruses
      were dominant). Emerging diseases were reported disproportionally in salmonid
      species (33%), in farmed populations (62%) and in Europe and North America (80%).
      The lack of reports from some regions with significant aquaculture or fishery
      production may indicate that emerging diseases are not being recognized in these
      areas owing to insufficient surveillance or testing or that these events are
      being under-reported. The results are discussed in relation to processes
      underpinning disease emergence in the aquatic environment.

PMID- 22136626
TI  - Off-hours admission for acute stroke is not associated with worse outcome--a
      nationwide Israeli stroke project.
AB  - BACKGROUND AND PURPOSE: Several studies reported worse outcome for stroke
      patients arriving on weekends. We compared working hours to off-work hours
      throughout the week as there is lack of experienced staff and special services
      during off-hours. METHODS: A nationwide stroke survey project on acute stroke was
      carried out in all acute care hospitals in Israel during 2004, 2007 and 2010 (2
      month each). 'On-hours' were defined as regular Israel working hours and the
      rest, including holidays, were defined as 'off-hours'. The modified Rankin scale
      (mRS) at discharge was used for the main analysis on outcome. RESULTS: A total of
      4827 acute strokes patients were analyzed (2139 arrived on-hours and 2688 during
      off-hours). 'Off-hours' patients were 1 year younger (mean 70 vs. 71 years in 'on
      hours') had lower rates of prior cardiac interventions, but had higher admission
      blood pressure levels and had more intracerebral hemorrhages (ICH) (11% vs. 8% in
      'on-hours' patients, P < 0.001). Death during hospitalization was recorded in 9%
      of 'off-hours' vs. 6% of 'on-hours' patient (P = 0.004). Controlling for age,
      blood pressure, stroke type, pre-stroke mRS, admission NIHSS, and thrombolysis,
      the relative odds of poor outcome (i.e. mRS >= 2) amongst 'off-hours' admissions
      compared to on-hours was 1.09 (95% CI: 0.92-1.30). Odds ratio amongst ischaemic
      stroke patients was 1.08 (95% CI: 0.88-1.33). CONCLUSIONS: Off-hours stroke
      admissions were associated with higher short-term mortality rate, probably due to
      a higher rate of ICH. After controlling for the latter and other potential
      confounders, 'off-hours' admissions were not different from 'on-hours' with
      respect to poor outcome.

PMID- 22136627
TI  - Structure and interactions of charged triblock copolymers studied by small-angle
      X-ray scattering: dependence on temperature and charge screening.
AB  - A series of thermo-responsive cationic triblock copolymers composed of methoxy
      poly(ethylene glycol) (MPEG, hydrophilic), poly(N-isopropylacrylamide) (PNIPAAM,
      temperature sensitive), and poly((3-acrylamidopropyl) trimethyl ammonium
      chloride) (PN(+), cationic) has been investigated as a function of temperature
      and ionic strength. In the MPEG-b-PNIPAAM-b-PN(+) copolymers, the MPEG block
      length is constant, and the lengths of the PNIPAAM and PN(+) blocks are varied.
      The solubility of the PNIPAAM block decreases with increasing temperature, and
      the triblock copolymer thus provides the possibilities of studying micelles with
      both neutral and charged blocks in the micelle corona as well as the interplay
      between these two blocks as the electrostatic interactions are varied by addition
      of salt. Investigation of the systems by densitometry and small-angle X-ray
      scattering (SAXS) in a temperature range from 20 to 70  degrees C gave detailed
      information on the behavior both below and above the critical micelle temperature
      (CMT). A clear effect of the addition of salt is observed in both the apparent
      partial specific volume, obtained from the densitometry measurements, and the
      SAXS data. Below the CMT, the single polymers can be described as Gaussian
      chains, for which the repulsive interchain interactions, originating from the
      charged PN(+) block, have to be taken into account in salt-free aqueous solution.
      Increasing the salt concentration of the solution to 30 mM NaCl leads to an
      increase in the apparent partial specific volume, and the electrostatic repulsive
      interchain interactions between the single polymers vanish. Raising the
      temperature results in micelle formation, except for the copolymer with only 20
      NIPAAM units. The SAXS data show that the polymer with the medium PNIPAAM block
      length forms spherical micelles, whereas the polymer with the longest PNIPAAM
      block forms cylindrical micelles. Increasing the temperature further above the
      CMT results in an increase in the micellar aggregation number for both of the
      polymers forming spherical and cylindrical micelles. The addition of salt to the
      solution also influences the aggregates formed above the CMT. Overall, the
      micelles formed in the salt solution have a smaller cross-section radius than
      those in aqueous solution without added salt.

PMID- 22136628
TI  - Direct cupration of fluoroform.
AB  - We have found the first reaction of direct cupration of fluoroform, the most
      attractive CF(3) source for the introduction of the trifluoromethyl group into
      organic molecules. Treatment of CuX (X = Cl, Br, I) with 2 equiv of MOR (M = K,
      Na) in DMF or NMP produces novel alkoxycuprates that readily react with CF(3)H at
      room temperature and atmospheric pressure to give CuCF(3) derivatives. The CuCl
      and t-BuOK (1:2) combination provides best results, furnishing the CuCF(3)
      product within seconds in nearly quantitative yield. As demonstrated, neither
      CF(3)(-) nor CF(2) mediate the Cu-CF(3) bond formation, which accounts for its
      remarkably high selectivity. The fluoroform-derived CuCF(3) solutions can be
      efficiently stabilized with TREAT HF to produce CuCF(3) reagents that readily
      trifluoromethylate organic and inorganic electrophiles in the absence of
      additional ligands such as phenanthroline. A series of novel Cu(I) complexes have
      been structurally characterized, including K(DMF)[Cu(OBu-t)(2)] (1),
      Na(DMF)(2)[Cu(OBu-t)(2)] (2), [K(8)Cu(6)(OBu-t)(12)(DMF)(8)(I)](+) I(-) (3), and
      [Cu(4)(CF(3))(2)(C(OBu-t)(2))(2)(MU(3)-OBu-t)(2)] (7).

PMID- 22136629
TI  - The predictive value of skin prick testing for challenge-proven food allergy: a
      systematic review.
AB  - Immunoglobulin E-mediated (IgE) food allergy affects 6-8% of children, and the
      prevalence is believed to be increasing. The gold standard of food allergy
      diagnosis is oral food challenges (OFCs); however, they are resource-consuming
      and potentially dangerous. Skin prick tests (SPTs) are able to detect the
      presence of allergen-specific IgE antibodies (sensitization), but they have low
      specificity for clinically significant food allergy. To reduce the need for OFCs,
      it has been suggested that children forgo an OFC if their SPT wheal size exceeds
      a cutoff that has a high predictability for food allergy. Although data for these
      studies are almost always gathered from high-risk populations, the 95% positive
      predictive values (PPVs) vary substantially between studies. SPT thresholds with
      a high probability of food allergy generated from these studies may not be
      generalizable to other populations, because of highly selective samples and
      variability in participant's age, test allergens, and food challenge protocol.
      Standardization of SPT devices and allergens, OFC protocols including
      standardized cessation criteria, and population-based samples would all help to
      improve generalizability of PPVs of SPTs.

PMID- 22136630
TI  - Effectiveness of activated carbon and biochar in reducing the availability of
      polychlorinated dibenzo-p-dioxins/dibenzofurans in soils.
AB  - Five activated carbons (ACs) and two biochars were tested as amendments to reduce
      the availability of aged polychlorinated dibenzo-p-dioxin/dibenzofurans (PCDD/Fs)
      in two soils. All sorbents (ACs and biochars) tested substantially reduced the
      availability of PCDD/Fs measured by polyoxymethylene (POM) passive uptake and
      earthworm (E. fetida) biouptake. Seven sorbents amended at a level of 0.2 * soil
      total organic carbon (0.2X) reduced the passive uptake (physicochemical
      availability) of total PCDD/Fs in POM by 40% to 92% (or toxic equivalent by 48%
      to 99%). Sorbents with finer particle sizes or more macropores showed higher
      reduction efficiencies. The powdered regenerated AC and powdered coconut AC
      demonstrated to be the most effective and the two biochars also performed
      reasonably well especially in the powdered form. The passive uptake of PCDD/F in
      POM increased approximately 4 to 5 fold as the contact time between POM and soil
      slurry increased from 24 to 120 d while the efficacy of ACs in reducing the
      physicochemical availability remained unchanged. The reduction efficiencies
      measured by POM passive uptake for the regenerated AC were comparable to those
      measured by earthworm biouptake (bioavailability) at both dose levels of 0.2X and
      0.5X. The biota-soil accumulation factor (BSAF) values for unamended soil ranged
      from 0.1 for tetra-CDD/F to 0.02 for octa-CDD/F. At both dose levels, the
      regenerated AC reduced the BSAFs to below 0.03 with the exception of two hexa
      CDD/Fs. The reduction efficiencies measured by earthworm for coconut AC and corn
      stover biochar were generally less than those measured by POM probably due to
      larger particle sizes of these sorbents that could not be ingested by the worms.

PMID- 22136631
TI  - Results of carbon ion radiotherapy for skin carcinomas in 45 patients.
AB  - BACKGROUND; Heavy ions represent the best tool for external radiotherapy (RT) of
      inoperable tumours. Heavy ion RT has been used in the treatment of various
      tumours, especially for radioresistant tumours mediated by hypoxia, localized
      near organs at risk. Most of these treatments are concentrated in deep-seated
      tumours such as those of the brain, head, lung, liver, rectum and urogenital
      organs, and treatment of skin carcinomas is limited. OBJECTIVES: To evaluate the
      outcome and toxicity after carbon ion RT for skin carcinomas at the Heavy Ion
      Research Facility in Lanzhou, China. METHODS: Between November 2006 and March
      2009, 45 patients with skin carcinoma [squamous cell carcinoma (SCC) (n = 16),
      basal cell carcinoma (BCC) (n = 12), malignant melanoma (MM) (n = 7), Bowen
      disease (n = 8) and Paget disease (n = 2)] were treated with carbon ion RT within
      a clinical Phase I trial. Patients received total doses of 60-70 GyE for SCC and
      BCC, 61-75 GyE for MM, 60 GyE for Bowen disease and 42.5 GyE for Paget disease,
      administered in 6-11 fractions over 6-11 days, with a fraction dose of 7-10 GyE.
      RESULTS: The mean follow-up was 24 months, range 12-36 months. The actuarial
      local control rates at 1 and 3 years were 90.9% and 65.5% for SCC, 91.7% and
      80.2% for BCC, 85.7% and 42.9% for MM, 90% and 90% for Bowen and Paget diseases,
      respectively. The actuarial 1- and 3-year overall survival rates for 45 patients
      were 88.9% and 86%, respectively. No severe side-effects greater than Common
      Toxicity Criteria grade 3 have been observed. CONCLUSIONS: The results
      demonstrated that heavy ion RT offers high local tumour control and progression
      free survival rates without significant radiation-induced toxicity for patients
      with skin carcinomas.

PMID- 22136632
TI  - Assessment of the intrinsic conformational preferences of dipeptide amino acids
      in aqueous solution by combined umbrella sampling/MBAR statistics. A comparison
      with experimental results.
AB  - The propensities of 19 amino acid dipeptides have been calculated by a
      distributed umbrella sampling molecular dynamics simulation procedure using the
      OPLS-AA force field. The potential of mean force maps was estimated with the
      multiple Bennett acceptance ratio statistics. The resulting propensities compare
      satisfactorily well with very recently published experimental data on equivalent
      systems. In particular, alpha conformation-probabilities for all of the
      dipeptides remain much lower than either beta or P(II) propensities. This result
      is in agreement with most experimental data for dipeptides. However, it is also
      in contrast with most simulation studies performed so far with other force
      fields, where alpha conformations result even more probable than P(II) or beta
      ones. We discuss the behavior of the OPLS-AA force field, which can be useful for
      the improvement of this model in reproducing the recent experimental observations
      on amino acid dipeptides.

PMID- 22136633
TI  - Isolated trisomy 7q21.2-31.31 resulting from a complex familial rearrangement
      involving chromosomes 7, 9 and 10.
AB  - BACKGROUND: Genotype-phenotype correlations for chromosomal imbalances are often
      limited by overlapping effects of partial trisomy and monosomy resulting from
      unbalanced translocations and by poor resolution of banding analysis for
      breakpoint designation. Here we report the clinical features of isolated partial
      trisomy 7q21.2 to 7q31.31 without overlapping phenotypic effects of partial
      monosomy in an 8 years old girl. The breakpoints of the unbalanced rearranged
      chromosome 7 could be defined precisely by array-CGH and a further imbalance
      could be excluded. The breakpoints of the balanced rearranged chromosomes 9 and
      10 were identified by microdissection of fluorescence labelled derivative
      chromosomes 9 and 10. RESULTS: The proband's mother showed a complex balanced
      translocation t(9;10)(p13;q23) with insertion of 7q21.2-31.31 at the
      translocation breakpoint at 9p13. The daughter inherited the rearranged
      chromosomes 9 and 10 but the normal chromosome 7 from her mother, resulting in
      partial trisomy 7q21.2 to 7q31.31. The phenotype of the patient consisted of
      marked developmental retardation, facial dysmorphism, short stature, strabism,
      and hyperextensible metacarpophalangeal joints. DISCUSSION: For better
      understanding of genotype-phenotype correlation a new classification of 7q
      duplications which will be based on findings of molecular karyotyping is needed.
      Therefore, the description of well-defined patients is valuable. This case shows
      that FISH-microdissection is of great benefit for precise breakpoint designation
      in balanced rearrangements.

PMID- 22136634
TI  - Characteristics of insulin secretion patterns in Japanese women with overt
      diabetes and gestational diabetes defined according to the International
      Association of Diabetes and Pregnancy Study Groups criteria.
AB  - AIM: To characterize patterns of insulin secretion in women with overt diabetes
      and gestational diabetes (GDM) defined by the International Association of
      Diabetes and Pregnancy Study Groups (IADPSG) criteria. MATERIAL AND METHODS: A
      total of 228 Japanese women were examined retrospectively. All 228 women had a
      positive 50-g glucose challenge test (GCT) result at 25.2+/-1.2weeks of gestation
      and underwent a 75-g glucose tolerance test (GTT) at 27.4+/-1.8weeks of
      gestation. The immunoreactive insulin levels were determined during the GTT in
      four groups of pregnant women: five with overt diabetes, 20 with GDM according to
      both the previous Japan Society of Gynecology and Obstetrics (JSOG) and current
      IADPSG criteria (traditional GDM group), 43 with GDM according to only the IADPSG
      criteria (new GDM group), and 160 with non- GDM, but with a positive GCT result.
      RESULTS: Attenuated and slow rise in plasma insulin in concert with prolonged
      hyperglycemia were characteristic in women with overt diabetes, compared with
      women with GDM in whom excessive insulin secretion in the presence of
      hyperglycemia was characteristic. The new GDM group did not differ significantly
      from the traditional GDM group with respect to scores of such indices as the
      insulinogenic index, the homeostasis model assessment for insulin resistance, and
      the quantitative insulin sensitivity check index. CONCLUSION: Women with overt
      diabetes have both an impaired capacity for insulin secretion and elevated
      insulin resistance, while women with GDM exhibit a maintained insulin secretory
      capacity with an elevated insulin resistance.

PMID- 22136635
TI  - Behavioral effects of congenital ventromedial prefrontal cortex malformation.
AB  - BACKGROUND: A detailed behavioral profile associated with focal congenital
      malformation of the ventromedial prefrontal cortex (vmPFC) has not been reported
      previously. Here we describe a 14 year-old boy, B.W., with neurological and
      psychiatric sequelae stemming from focal cortical malformation of the left vmPFC.
      CASE PRESENTATION: B.W.'s behavior has been characterized through extensive
      review Patience of clinical and personal records along with behavioral and
      neuropsychological testing. A central feature of the behavioral profile is severe
      antisocial behavior. He is aggressive, manipulative, and callous; features
      consistent with psychopathy. Other problems include: egocentricity, impulsivity,
      hyperactivity, lack of empathy, lack of respect for authority, impaired moral
      judgment, an inability to plan ahead, and poor frustration tolerance.
      CONCLUSIONS: The vmPFC has a profound contribution to the development of human
      prosocial behavior. B.W. demonstrates how a congenital lesion to this cortical
      region severely disrupts this process.

PMID- 22136636
TI  - Dietary habits and prostate cancer prevention: a review of observational studies
      by focusing on South America.
AB  - There exist several works considering the association between diet and prostate
      cancer (PC) risk, but the issue is largely unsettled. This article systematically
      reviews the epidemiological studies on diet and risk of PC focusing on those
      carried out in countries of South America. There is some suggestion that dairy
      products, red meat, processed meat, alpha-linolenic fatty acids, as well as
      dietary patterns characterized by higher intakes of red and processed meat, eggs,
      and grains may play some role in the development of PC. There is no clear
      association with the intake of vegetables and fruits, lycopene, fats, and
      different types of fatty acids. The evidence on diet and PC is therefore
      inconclusive in general and specifically in South America. Particular attention
      must be paid to the study of cancer risk in some countries of South America
      because of the singularly risky dietary pattern consumed by its population.

PMID- 22136637
TI  - Toward systems biology in brown algae to explore acclimation and adaptation to
      the shore environment.
AB  - Brown algae belong to a phylogenetic lineage distantly related to land plants and
      animals. They are almost exclusively found in the intertidal zone, a harsh and
      frequently changing environment where organisms are submitted to marine and
      terrestrial constraints. In relation with their unique evolutionary history and
      their habitat, they feature several peculiarities, including at the level of
      their primary and secondary metabolism. The establishment of Ectocarpus
      siliculosus as a model organism for brown algae has represented a framework in
      which several omics techniques have been developed, in particular, to study the
      response of these organisms to abiotic stresses. With the recent publication of
      medium to high throughput profiling data, it is now possible to envision
      integrating observations at the cellular scale to apply systems biology
      approaches. As a first step, we propose a protocol focusing on integrating
      heterogeneous knowledge gained on brown algal metabolism. The resulting
      abstraction of the system will then help understanding how brown algae cope with
      changes in abiotic parameters within their unique habitat, and to decipher some
      of the mechanisms underlying their (1) acclimation and (2) adaptation,
      respectively consequences of (1) the behavior or (2) the topology of the system
      resulting from the integrative approach.

PMID- 22136639
TI  - Models and tools for studying drought stress responses in peas.
AB  - The pea (Pisum sativum L.) is an important pulse crop but the growing area is
      limited because of its relatively low yield stability. In many parts of the world
      the most important abiotic factor limiting the survival and yield of plants is
      the restricted water supply, and the crop productivity can only be increased by
      improving drought tolerance. Development of pea cultivars well adapted to dry
      conditions has been one of the major tasks in breeding programs. Conventional
      breeding of new cultivars for dry conditions required extensive selection and
      testing for yield performance over diverse environments using various biometrical
      approaches. Several morphological and biochemical traits have been proven to be
      related to drought resistance, and methods based on physiological attributes can
      also be used in development of better varieties. Osmoregulation plays a role in
      the maintenance of turgor pressure under water stress conditions, and information
      on the behaviour of genotypes under osmotic stress can help selection for drought
      resistance. Biotechnological approaches including in vitro test, genetic
      transformation, and the use of molecular markers and mutants could be useful
      tools in breeding of pea. In this minireview we summarized the present status of
      different approaches related to drought stress improvement in the pea.

PMID- 22136640
TI  - A strategy for the identification of new abiotic stress determinants in
      Arabidopsis using web-based data mining and reverse genetics.
AB  - Since the sequencing of the Arabidopsis thaliana genome in 2000, plant
      researchers have faced the complex challenge of assigning function to thousands
      of genes. Functional discovery by in silico prediction or homology search
      resolved a significant number of genes, but only a minor part has been
      experimentally validated. Arabidopsis entry into the post-genomic era signified a
      massive increase in high-throughput approaches to functional discovery, which
      have since become available through publicly-available web-based resources. The
      present work focuses on an easy and straightforward strategy that couples data
      mining to reverse genetics principles, to allow for the identification of new
      abiotic stress determinant genes. The strategy explores systematic microarray
      based transcriptomics experiments, involving Arabidopsis abiotic stress
      responses. An overview of the most significant resources and databases for
      functional discovery in Arabidopsis is presented. The successful application of
      the outlined strategy is illustrated by the identification of a new abiotic
      stress determinant gene, HRR, which displays a heat-stress-related phenotype
      after a loss-of-function reverse genetics approach.

PMID- 22136638
TI  - SnRK2 protein kinases--key regulators of plant response to abiotic stresses.
AB  - The SnRK2 family members are plant-specific serine/threonine kinases involved in
      plant response to abiotic stresses and abscisic acid (ABA)-dependent plant
      development. SnRK2s have been classed into three groups; group 1 comprises
      kinases not activated by ABA, group 2 comprises kinases not activated or
      activated very weakly by ABA, and group 3 comprises kinases strongly activated by
      ABA. So far, the ABA-dependent kinases belonging to group 3 have been studied
      most thoroughly. They are considered major regulators of plant response to ABA.
      The regulation of the plant response to ABA via SnRK2s pathways occurs by direct
      phosphorylation of various downstream targets, for example, SLAC1, KAT1, AtRbohF,
      and transcription factors required for the expression of numerous stress response
      genes. Members of group 2 share some cellular functions with group 3 kinases;
      however, their contribution to ABA-related responses is not clear. There are
      strong indications that they are positive regulators of plant responses to water
      deficit. Most probably they complement the ABA-dependent kinases in plant defense
      against environmental stress. So far, data concerning the physiological role of
      ABA-independent SnRK2s are very limited; it is to be expected they will be
      studied extensively in the nearest future.

PMID- 22136641
TI  - Glioma spheroids.

PMID- 22136642
TI  - Increased rate of complications on a neurological surgery service after
      implementation of the Accreditation Council for Graduate Medical Education work
      hour restriction.
AB  - OBJECT: The Accreditation Council for Graduate Medical Education instituted
      mandatory 80-hour work-week limitations in July 2003. The work-hour restriction
      was met with skepticism among the academic neurosurgery community and is thought
      to represent a barrier to teaching, ultimately compromising patient care. The
      authors hypothesize that the introduction of the mandatory resident work-hour
      restriction corresponds with an overall increase in morbidity rate. METHODS: This
      study compares the morbidity and mortality rates on an academic neurological
      surgery service before and after institution of the work-hour restriction.
      Complications are individually assessed at a monthly divisional conference by
      neurosurgical faculty and residents. A prospective database was commenced in July
      2000 recording all complications, complications that were deemed to be
      potentially avoidable ("possibly preventable"), and complications that were
      deemed unavoidable. The incidence of morbidity and mortality from July 2000 to
      June 2003 is compared with the incidence from July 2003 to June 2006. RESULTS:
      The overall rate of morbidity and mortality increased from 103 to 114 per 1000
      patients treated after institution of the work-hour restriction, although this
      increase was not statistically significant (chi(2)(1, N = 8546) = 2.6, p =
      0.106). The morbidity rate increased from 70 to 89 per 1000 patients treated
      after institution of the work-hour restriction (chi(2)(1, N = 8546) = 10, p =
      0.001). The overall mortality rate was diminished from 32 to 27 per 1000 patients
      treated after institution of the work-hour restriction (chi(2)(1, N = 8546) =
      3.2, p = 0.075). Morbidities considered avoidable or possibly preventable were
      seen to increase from 56 to 66 per 1000 patients treated (chi(2)(1, N = 8546) =
      5.7, p = 0.017). Avoidable or possibly preventable mortalities numbered 3 per
      1000 patients treated, and this rate did not change after introduction of the
      work-hour restriction (chi(2)(1, N = 8546) = 0.08, p = 0.777). CONCLUSIONS: The
      morbidity rate on a neurological surgery service is increased after
      implementation of the work-hour restriction. Mortality rates remain unchanged.

PMID- 22136643
TI  - Resident work hours.

PMID- 22136644
TI  - Intracranial hemorrhage after removal of deep brain stimulation electrodes.
AB  - OBJECT: Many previous studies have shown that placement of deep brain stimulation
      (DBS) electrodes carries a considerable risk of hemorrhage. To date, no studies
      have evaluated the incidence of intracranial hemorrhage after removal of DBS
      electrodes. The authors performed a retrospective chart review to identify the
      incidence and trends in hemorrhage after DBS electrode removal. METHODS: A
      retrospective chart review of all DBS electrodes removed at the Cleveland Clinic
      between October 2000 and May 2010 was performed. All patients underwent
      postoperative CT scanning. Each patient was evaluated for age, sex, side of
      placement, target, duration of lead placement, reason for removal, and medical
      comorbidities. RESULTS: A total of 78 lead removals were performed in the 10-year
      period (1300 leads were implanted during the same period). Of the 78 leads
      removed, 10 (12.8%) resulted in hemorrhages seen on postoperative CT scans. The
      hemorrhages were superficial cortical in 6 cases of lead removal (60%) and deep
      in 4 cases (40%). No statistically significant correlation to any of the factors
      evaluated was found. All hemorrhages were asymptomatic. The authors'
      retrospective study of 78 DBS lead removals revealed a high risk of intracranial
      hemorrhage (12.8% per lead). The risk of hemorrhage during removal is
      significantly greater than the risk of hemorrhage during implantation (2.0% per
      lead at the authors' center during the same period). There were more superficial
      hemorrhages, and all hemorrhages were asymptomatic. CONCLUSIONS: Removal of DBS
      leads carries a significantly higher risk of postoperative hemorrhages that are
      seen on images but are not clinically symptomatic.

PMID- 22136645
TI  - The effect of call on neurosurgery residents' skills: implications for policy
      regarding resident call periods.
AB  - OBJECT: Although fatigue and its effects on surgical proficiency have been an
      actively researched area, previous studies have not examined the effect of
      fatigue on neurosurgery residents specifically. This study aims to quantify the
      effect of fatigue on the psychomotor and cognitive skills of neurosurgery
      residents. METHODS: Seven neurosurgery residents performed a minimum of 3 and a
      maximum of 4 sessions of 6 surgical exercises precall and postcall. The
      simulation exercises were designed to measure a surgeon's cognitive abilities,
      such as memory and attention, while performing simulated surgical tasks and
      exercises that have been previously validated in several studies, including
      studies measuring the impact of fatigue on general surgery residents. Each
      exercise measured tool-movement smoothness, time elapsed, and cognitive errors.
      The change in surgical skills in precall and postcall conditions was assessed by
      means of an ANOVA, with p < 0.05 considered statistically significant. RESULTS:
      The neurosurgery residents did not show a statistically significant difference in
      their surgical skills between the pre- and postcall states (p < 0.3, p < 0.4, and
      p < 0.2 for movement smoothness, time elapsed, and cognitive errors,
      respectively). The mean decrement for all residents in the postcall condition was
      13.1%. CONCLUSIONS: Postcall fatigue is associated with a marginal decrease in
      proficiency during simulated surgery in neurosurgery residents. In a similar
      study, general surgery residents showed a statistically significant decrement of
      27.3% in the postcall condition. The impact of fatigue on different specialties
      should be further investigated prior to implementation of a national physician
      work-hour policy.

PMID- 22136646
TI  - Artificially depleted plasmas are not necessarily commutable with native patient
      plasmas for International Sensitivity Index calibration and International
      Normalized Ratio derivation.

PMID- 22136647
TI  - Isothermal evaporation of ethanol in a dynamic gas atmosphere.
AB  - Optimization of evaporation and pyrolysis conditions for ethanol are important in
      carbon nanotube (CNT) synthesis. The activation enthalpy (DeltaH(?)), the
      activation entropy (DeltaS(?)), and the free energy barrier (DeltaG(?)) to
      evaporation have been determined by measuring the molar coefficient of
      evaporation, k(evap), at nine different temperatures (30-70  degrees C) and four
      gas flow rates (25-200 mL/min) using nitrogen and argon as carrier gases. At 70 
      degrees C in argon, the effect of the gas flow rate on k(evap) and DeltaG(?) is
      small. However, this is not true at temperatures as low as 30  degrees C, where
      the increase of the gas flow rate from 25 to 200 mL/min results in a nearly 6
      times increase of k(evap) and decrease of DeltaG(?) by ~5 kJ/mol. Therefore, at
      30  degrees C, the effect of the gas flow rate on the ethanol evaporation rate is
      attributed to interactions of ethanol with argon molecules. This is supported by
      simultaneous infrared spectroscopic analysis of the evolved vapors, which
      demonstrates the presence of different amounts of linear and cyclic hydrogen
      bonded ethanol aggregates. While the amount of these aggregates at 30  degrees C
      depends upon the gas flow rate, no such dependence was observed during
      evaporation at 70  degrees C. When the evaporation was carried out in nitrogen,
      DeltaG(?) was almost independent of the evaporation temperature (30-70  degrees
      C) and the gas flow rate (25-200 mL/min). Thus the evaporation of ethanol in a
      dynamic gas atmosphere at different temperatures may go via different mechanisms
      depending on the nature of the carrier gas.

PMID- 22136649
TI  - Effect of ultrahigh hydrostatic pressure on the activity and structure of
      mushroom (Agaricus bisporus) polyphenoloxidase.
AB  - High hydrostatic pressure (HHP, treatment pressure <=700 MPa) is approved to be
      the most successful commercial nonthermal processing due to its minimal
      modifications in nutritional and sensory quality. However, for some pressure
      stable enzymes such as PPO, this unique technology can hardly inactivate them at
      treatment pressure below of 700 MPa. This study investigated the effects of
      ultrahigh hydrostatic pressure (UHHP, treatment pressure >700 MPa) on the
      activity of Agaricus bisporus mushroom polyphenoloxidase (PPO) both in the
      phosphate buffer and in the mushroom puree, and on the structure of the enzyme by
      means of circular dichroism (CD), fluorescence emission spectra, and sulphydryl
      group detection. The results showed that UHHP treatment at pressure from 800 to
      1600 MPa caused significant inactivation on the PPO both in the phosphate buffer
      and in the mushroom puree. UHHP treatment at 1400 and 1600 MPa for 1 min reduced
      the enzyme activity by 90.4% and 99.2% in the buffer;, however, higher enzyme
      activity remained in the puree after UHHP treatment at the same condition. CD and
      fluorescence spectra analysis showed that the secondary and tertiary structures
      of UHHP treated mushroom PPO were changed. The sulphydryl group (SH) detection
      revealed that the SH content on the surface of UHHP treated mushroom PPO was
      increased. It has been suggested that the inactivation of mushroom PPO by UHHP
      treatment at pressure higher than 1000 MPa was due to the synergistic effect of
      the pressure and the heat arising from pressurization, in which heat plays a
      major role.

PMID- 22136650
TI  - Guiding principles for printed education materials: design preferences of people
      with aphasia.
AB  - The objectives of this study were to obtain the preferences of people with
      aphasia for the design of stroke and aphasia printed education materials (PEMs)
      and to compare these preferences with recommendations in the literature for
      developing written information for other populations. A face-to-face quantitative
      questionnaire was completed with 40 adults with aphasia post-stroke. The
      questionnaire explored preferences for: (1) the representation of numbers, (2)
      font size and type, (3) line spacing, (4) document length, and (5) graphic type.
      Most preferences (62.4%, n = 146) were for numbers expressed as figures rather
      than words. The largest proportion of participants selected 14 point (28.2%, n =
      11) and Verdana ref (33.3%, n = 13) as the easiest font size and type to read,
      and a preference for 1.5 line spacing (41.0%, n = 16) was identified. Preference
      for document length was not related to the participant's reading ability or
      aphasia severity. Most participants (95.0%, n = 38) considered graphics to be
      helpful, with photographs more frequently reported as a helpful graphic type. The
      identified preferences support many of the formatting recommendations found
      within the literature. This research provides guiding principles for developing
      PEMs in preferred formats for people with aphasia.

PMID- 22136651
TI  - A molecular linkage map for Drosophila mediopunctata confirms synteny with
      Drosophila melanogaster and suggests a region that controls the variation in the
      number of abdominal spots.
AB  - The classic approach to gene discovery relies on the construction of linkage
      maps. We report the first molecular-based linkage map for Drosophila
      mediopunctata, a neotropical species of the tripunctata group. Eight hundred F(2)
      individuals were genotyped at 49 microsatellite loci, resulting in a map that is
      ~450 centimorgans long. Five linkage groups were detected, and the species'
      chromosomes were identified through cross-references to BLASTn searches and
      Muller elements. Strong synteny was observed when compared with the Drosophila
      melanogaster chromosome arms, but little conservation in the gene order was seen.
      The incorporation of morphological data corresponding to the number of central
      abdominal spots on the map was consistent with the expected location of a genomic
      region responsible for the phenotype on the second chromosome.

PMID- 22136652
TI  - Silicon supply modifies C:N:P stoichiometry and growth of Phragmites australis.
AB  - Silicon is a non-essential element for plant growth. Nevertheless, it affects
      plant stress resistance and in some plants, such as grasses, it may substitute
      carbon (C) compounds in cell walls, thereby influencing C allocation patterns and
      biomass production. How variation in silicon supply over a narrow range affects
      nitrogen (N) and phosphorus (P) uptake by plants has also been investigated in
      some detail. However, little is known about effects on the stoichiometric
      relationships between C, N and P when silicon supply varies over a broader range.
      Here, we assessed the effect of silicon on aboveground biomass production and
      C:N:P stoichiometry of common reed, Phragmites australis, in a pot experiment in
      which three widely differing levels of silicon were supplied. Scanning electron
      microscopy (SEM) showed that elevated silicon supply promoted silica deposition
      in the epidermis of Phragmites leaves. This resulted in altered N:P ratios,
      whereas C:N ratios changed only slightly. Plant growth was slightly (but not
      significantly) enhanced at intermediate silicon supply levels but significantly
      decreased at high levels. These findings point to the potential of silicon to
      impact plant growth and elemental stoichiometry and, by extension, to affect
      biogeochemical cycles in ecosystems dominated by Phragmites and other grasses and
      sedges.

PMID- 22136653
TI  - The interruptive effect of pain on attention.
AB  - Pain is known to disrupt attentional performance in both healthy adults and
      patients with chronic pain. Exactly which aspects of attentional function are
      affected are, however, still to be determined. The primary aim of this
      investigation was to systematically examine the effects of experimentally induced
      pain on a range of attentional performance tasks. Following a review of tests of
      attentional disruption, seven best candidate tasks were selected and examined
      across seven experiments. The tasks were: continuous performance, flanker,
      endogenous precueing, n-back, inhibition, attentional switching, and divided
      attention. Healthy adult participants performed each of these tasks under three
      different conditions: a painful heat sensation, a warm heat sensation, and a
      nonheat control. Pain differentially affected attentional performance across
      these tasks; pain-related attentional impairment was found on the n-back,
      attentional switching, and divided attention tasks, but not on the other tasks.
      This finding suggests that the aspects of attention most affected by pain are
      those essential for the completion of complex tasks that require the processing
      of multiple cues and control over attentional deployment. These results are
      discussed in the context of an emerging view of pain as a demand for executive
      control and the development of measures that could be used to examine attentional
      disruption in the context of pain.

PMID- 22136654
TI  - Synthesis of 2-(polyfluoroaryl)benzofurans via a copper(I)-catalyzed reaction of
      2-(2,2-dibromovinyl)phenol with polyfluoroarene.
AB  - A novel and efficient route for the synthesis of 2-(polyfluoroaryl)benzofurans
      via a copper(I)-catalyzed tandem reaction of 2-(2,2-dibromovinyl)phenol with
      polyfluoroarene is reported. The corresponding products are generated in good
      yields. During the reaction process, a copper-catalyzed intramolecular C-O bond
      formation and a C-H activation are involved.

PMID- 22136648
TI  - Convergent mechanisms in etiologically-diverse dystonias.
AB  - INTRODUCTION: Dystonia is a neurological disorder associated with twisting
      motions and abnormal postures, which compromise normal movements and can be both
      painful and debilitating. It can affect a single body part (focal), several
      contiguous regions (segmental), or the entire body (generalized), and can arise
      as a result of numerous causes, both genetic and acquired. Despite the diversity
      of causes and manifestations, shared clinical features suggest that common
      mechanisms of pathogenesis may underlie many dystonias. AREAS COVERED: Shared
      themes in etiologically-diverse dystonias exist at several biological levels. At
      the cellular level, abnormalities in the dopaminergic system, mitochondrial
      function and calcium regulation are often present. At the anatomical level, the
      basal ganglia and the cerebellum are frequently implicated. Global CNS
      dysfunction, specifically aberrant neuronal plasticity, inhibition and
      sensorimotor integration, are also observed in a number of dystonias. Using
      clinical data and data from animal models, this article seeks to highlight shared
      pathways that may be critical in understanding mechanisms and identifying novel
      therapeutic strategies in dystonia. EXPERT OPINION: Identifying shared features
      of pathogenesis can provide insight into the biological processes that underlie
      etiologically diverse dystonias, and can suggest novel targets for therapeutic
      intervention that may be effective in a broad group of affected individuals.

PMID- 22136655
TI  - Computational evidence for alpha-nitrosamino radical as initial metabolite for
      both the P450 dealkylation and denitrosation of carcinogenic nitrosamines.
AB  - The mutagenic and carcinogenic potency of alpha-CH(n)-nitrosamines such as N
      nitrosodimethylamine (NDMA) is caused by their P450-catalyzed alpha-hydroxylation
      and subsequent dealkylation, yielding alkyl diazonium ions (R-N=N(+)) as potent
      electrophiles. Alternatively, P450s may also catalyze their denitrosation as
      metabolic detoxification. DFT calculations at the UB3LYP/LANL2DZ(Fe)/6
      31G+**(H,C,N,O,S)//LANL2DZ(Fe)/6-31G(H,C,N,O,S) level of theory show that H
      abstraction from the alpha-C of NDMA as initial metabolic step yields an alpha
      nitrosamino radical (*CH(2)N(CH(3))NO) as common first intermediate for both the
      oxidative dealkylation (toxification) and denitrosation (detoxification)
      pathways. In particular, the calculated kinetic isotope effect for the P450
      mediated dealkylation of NDMA is in good agreement with experimental information.
      The results show further that the initial alpha-hydroxylation of NDMA may proceed
      in two spin states. Besides a stepwise high-spin (HS, quartet) route with a
      separate rebound barrier, there is a concerted low-spin (LS, doublet) pathway.
      Interestingly, the resultant two-state reactivity appears to discriminate between
      metabolic toxification and detoxification: Evaluation of calculated free energy
      barriers of the H-abstraction (DeltaG(?)) through the Eyring equation suggests
      that the dealkylation:denitrosation product ratio is governed by the LS:HS ratio
      of the overall metabolic process. Moreover, inclusion of three further alpha
      CH(n)-nitrosamines in the computational analysis demonstrates that the initial H
      abstraction barrier is proportional to the C-H bond dissociation enthalpy (BDE)
      of the substrates, which enables the estimation of spin-averaged reaction
      barriers through ground-state BDE calculations. The discussion includes also
      reductive denitrosation pathways that according to current computational evidence
      appear to be unlikely for aliphatic nitrosamines.

PMID- 22136656
TI  - Identification of new peptide ligands for epidermal growth factor receptor using
      phage display and computationally modeling their mode of binding.
AB  - Peptide phage display, a powerful method for ligand identification, was used to
      identify new peptide ligands for epidermal growth factor receptor. A-431 cells
      expressing epidermal growth factor receptor were used as the matrix in a cell
      based subtractive biopanning approach using a 7-mer peptide displaying phage
      library. Two novel peptide ligands were identified and tested for their
      affinities and functional effects on epidermal growth factor receptor. The
      identified peptides were able to inhibit the epidermal growth factor-induced
      phosphorylation of epidermal growth factor receptor in a concentration-dependent
      manner. The results of affinity binding experiments showed that the natural
      ligand, that is epidermal growth factor, was able to inhibit competitively the
      binding of peptide-bearing phage to epidermal growth factor receptor expressing A
      431 cells. Molecular modeling studies were used to calculate the free energies
      for the binding of peptides to the receptor-binding site as well as proposing the
      interaction modes for this binding. The calculated values for the binding
      energies were found to be similar to our experimental data and those of
      previously reported studies.

PMID- 22136657
TI  - Regeneration of native-like neo-urinary tissue from nonbladder cell sources.
AB  - Urinary pathology requiring urinary diversion, partial or full bladder
      replacement, is a significant clinical problem affecting ~14,000 individuals
      annually in the United States alone. The use of gastrointestinal tissue for
      urinary diversion or bladder reconstruction/replacement surgeries is frequently
      associated with complications. To try and alleviate or reduce the frequency of
      these complications, tissue engineering and regenerative medicine strategies have
      been developed using bio-absorbable materials seeded with cells derived from the
      bladder. However, bladder-sourced cells may not always be suitable for such
      applications, especially in patients with bladder cancer. In this study, we
      describe the isolation and characterization of smooth muscle cells (SMCs) from
      porcine adipose and peripheral blood that are phenotypically and functionally
      indistinguishable from bladder-derived SMCs. In a preclinical Good Laboratory
      Practice study, we demonstrate that autologous adipose- and peripheral blood
      derived SMCs may be used to seed synthetic, biodegradable tubular scaffold
      structures and that implantation of these seeded scaffolds into a porcine
      cystectomy model leads to successful de novo regeneration of a tubular neo-organ
      composed of urinary-like neo-tissue that is histologically identical to native
      bladder. The ability to create urologic structures de novo from scaffolds seeded
      by autologous adipose- or peripheral blood-derived SMCs will greatly facilitate
      the translation of urologic tissue engineering technologies into clinical
      practice.

PMID- 22136658
TI  - Risk of obstetric and thromboembolic complications in family members of women
      with previous adverse obstetric outcomes carrying common inherited thombophilias.
AB  - BACKGROUND: Factor (F)V Leiden and the prothrombin 20210A mutation (PTm) are
      associated with the occurrence of obstetric complications, including pregnancy
      related venous thromboembolism (VTE). It is not known whether family members of
      women with FV Leiden or PTm and previous obstetric complications have a higher
      risk of VTE or adverse obstetric outcomes. METHODS: A retrospective family study
      including 563 relatives of 177 women with previous adverse outcomes carrying FV
      Leiden or PTm, referred between April 1993 and June 2010. A history of obstetric
      complications and VTE was obtained. Prevalence of VTE and obstetric complications
      in relatives with and without inherited thrombophilias was compared. Adjusted odd
      ratios (OR) and 95% confidence intervals (CI) were calculated using logistic
      regression models that controlled for predictors (age, FV Leiden and PTm).
      RESULTS: Relatives carrying FV Leiden had a significant and independent risk for
      obstetric complications (OR: 1.98, 95% CI 1.03-3.83); this risk was not observed
      in the presence of PTm (OR: 1.03, 95% CI 0.46-2.32). The presence of FV Leiden or
      PTm in heterozygosis was significantly and independently associated with the
      occurrence of VTE (OR: 5.2, 95% CI: 1.70-15.91). Severe thrombophilias were
      strong risk factors for VTE (OR: 23.2, 95% CI: 6.0-89.85). Male gender was a
      significant and independent risk factor for VTE (OR: 3.49, 95% CI: 1.51-8.05).
      The risk did not change when relatives of women with a previous pregnancy-related
      VTE were excluded (OR: 3.49, 95% CI: 1.51-8.05). CONCLUSIONS: Knowledge of
      thrombophilia status may help to better define the obstetric and thromboembolic
      risks in asymptomatic family members of women who suffered from obstetric
      complications.

PMID- 22136660
TI  - Prenatal administration of Lactobacillus rhamnosus has no effect on the diversity
      of the early infant gut microbiota.
AB  - We have recently shown that maternal administration of Lactobacillus rhamnosus GG
      (LGG) during late pregnancy can have beneficial effects on the early development
      of infant gut microbiota, promoting a bifidobacteria profile similar to that of a
      healthy breastfed infant. It is uncertain, however, whether such probiotic
      supplementation could influence the diversity of infant gut microbiota. We
      investigated the effect of pre-natal LGG on gut microbial diversity in the early
      post-natal period. Day-7 faecal samples were collected from 98 infants at high
      risk of allergic disease, whose mothers participated in a pre-natal probiotic
      eczema prevention study. Faecal microbial diversity was assessed by terminal
      restriction fragment length polymorphism using restriction enzymes Sau96I and
      AluI. A greater number of peaks represent greater diversity of bacterial
      communities. Administration of LGG to mothers during late pregnancy had no
      effects on the mean number of peaks in faecal samples from 1-wk-old infants as
      compared to placebo (AluI 14.4 vs. 15.5, p = 0.17, 95% CI -0.4, 2.5; Sau96I 17.3
      vs. 15.8, p = 0.15, 95% CI -3.5, 0.5). Prenatal LGG failed to modulate diversity
      of early infant gut microbiota despite promoting a beneficial bifidobacteria
      profile.

PMID- 22136659
TI  - STAT3 activation in monocytes accelerates liver cancer progression.
AB  - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is an
      important transcription factor ubiquitously expressed in different cell types.
      STAT3 plays an essential role in cell survival, proliferation, and
      differentiation. Aberrantly hyper-activated STAT3 signaling in cancer cells and
      in the tumor microenvironment has been detected in a wide variety of human
      cancers and is considered an important factor for cancer initiation, development,
      and progression. However, the role of STAT3 activation in monocytes in the
      development of HCC has not been well understood. METHODS: Immunohistochemical
      analysis of phosphorylated STAT3 was performed on tissue microarray from HCC
      patients. Using a co-culture system in vivo, HCC cell growth was determined by
      the MTT assay. In vivo experiments were conducted with mice given
      diethylinitrosamine (DEN), which induces HCC was used to investigate the role of
      STAT3 expression in monocytes on tumor growth. Real-time PCR was used to
      determine the expression of cell proliferation and cell arrest associated genes
      in the tumor and nontumor tissue from liver. RESULTS: Phosphorylated STAT3 was
      found in human hepatocellular carcinoma tissue samples and was expressed in tumor
      cells and also in monocytes. Phosphorylated STAT3 expression in monocyte was
      significantly correlated to advanced clinical stage of HCC and a poor prognosis.
      Using a co-culture system in vivo, monocytes promoted HCC cell growth via the IL
      6/STAT3 signaling pathway. The STAT3 inhibitor, NSC 74859, significantly
      suppressed tumor growth in vivo in mice with diethylinitrosamine (DEN)-induced
      HCC. In this animal model, blockade of STAT3 with NSC 74859 induced tumor cell
      apoptosis, while inhibiting both tumor cells and monocytes proliferation.
      Furthermore, NSC 74859 treatment suppressed cancer associated inflammation in DEN
      induce HCC. CONCLUSION: Our data suggest constitutively activated STAT3 monocytes
      promote liver tumorigenesis in clinical patients and animal experiments. Thus,
      STAT3 in tumor infiltrating inflammatory cells may an attractive target for liver
      cancer therapy.

PMID- 22136661
TI  - Mercury in municipal solid waste in China and its control: a review.
AB  - Although a potentially significant and preventable source of environmental
      pollution, mercury in municipal solid waste (MSW) has not received adequate
      attention in China. Discarded mercury-containing products, if not recycled,
      ultimately release mercury to air, soil, and groundwater, even after being
      properly collected and disposed of in MSW management facilities. This review
      presents an overview on mercury in MSW and describes the emissions associated
      with landfilling, incineration, and composting in China. Besides end-of-pipe
      technologies for controlling mercury emissions from MSW management, strategies
      for controlling mercury in MSW are also discussed, focusing on mercury source
      reduction and recycling. Batteries and fluorescent lamps contribute to
      approximately three-quarters of mercury in MSW, and are expected to remain as
      significant sources of mercury in the near future. Reducing or eliminating the
      mercury contents in household products, particularly batteries and fluorescent
      lamps, should be the top priority in controlling mercury in MSW, while it is also
      important to set mercury contents in consumer products at acceptable and
      achievable levels based on a life-cycle approach. Meanwhile, cost-effective
      recycling programs should be developed targeting products containing elemental
      mercury, such as medical thermometers and sphygmomanometers, and waste products
      with high mercury contents (e.g., button cells) as well.

PMID- 22136662
TI  - A European multicentre reappraisal of distal compound muscle action potential
      duration in chronic inflammatory demyelinating polyneuropathy.
AB  - BACKGROUND: The electrodiagnostic value of distal compound muscle action
      potential duration (DCMAPD) has been studied rarely in chronic inflammatory
      demyelinating polyneuropathy (CIDP). Cut-offs proposed have not been widely
      evaluated. The influence of low-cut EMG filter settings <= 10 Hz as used in
      Europe is uncertain. METHODS: We retrospectively reviewed records of 110 patients
      with typical, treatment-responsive CIDP, from Leicester, U.K., Paris and Angers,
      France. All fulfilled revised European Federation of Neurological
      Societies/Peripheral Nerve Society (EFNS/PNS) clinical and electrodiagnostic
      criteria for typical CIDP (2010), before consideration of DCMAPD prolongation.
      Results were compared with those of 110 controls with chronic sensory/sensory
      motor axonal neuropathy. We constructed receiver operating characteristic (ROC)
      curves for each nerve and derived cut-offs for DCMAPD prolongation, offering
      specificity of >= 98% vs. controls. RESULTS: DCMAPD was significantly greater in
      all nerves for CIDP patients, compared with controls (P < 0.001). ROC curves
      allowed derivation of cut-offs of sensitivities ranging from 27.1% (ulnar nerve)
      to 60% (tibial nerve). Using these cut-offs to define DCMAPD prolongation in any
      studied motor nerve offered a sensitivity of 69.1% for CIDP and specificity of
      97.3% vs. controls. CONCLUSION: Cut-offs for DCMAPD are dependent on EMG filter
      settings. DCMAPD prolongation in any motor nerve, using our derived cut-offs,
      represents a sensitive and specific marker of CIDP in patients studied with EMG
      equipment with low-cut filter settings <= 10 Hz. Appropriate use of this
      parameter appears an essential criterion to consider in assessing suspected CIDP,
      which may be helpful in limiting extensiveness and duration of
      electrophysiological testing, thereby reducing patient discomfort.

PMID- 22136663
TI  - Omics of root-to-shoot signaling under salt stress and water deficit.
AB  - Maximizing crop yield depends on the leaves receiving an optimal supply of water,
      mineral nutrients, small organic molecules, proteins, and hormones from the root
      system via the xylem. Soil drying and salinization alter these xylem fluxes, and
      modern omics techniques offer unparalleled opportunities to understand the
      complexity of these responses. Although absolute xylem concentrations of any
      constituent depend on the genotype and xylem sap sampling methodology, analysis
      of the relative changes in concentrations has revealed some conserved behavior.
      Typically, these stresses increase xylem concentrations of the plant hormone
      abscisic acid (ABA) that limits crop water loss, but decrease the concentrations
      of certain cytokinins that stimulate expansive growth and prevent premature leaf
      senescence. Further understanding of the ionic and biophysical alterations in the
      rhizosphere environment that cause increased xylem concentrations of the ethylene
      precursor (ACC) is needed. Interactions of these plant hormones with plant
      nutrient status and xylem nutrient delivery may be important in tuning plant
      responses to their environment. Xylem proteomics is an emerging area that will
      help understand mechanisms of plant stress adaptation. Using omics techniques to
      underpin rootstock-mediate plant improvement is likely to improve crop yields in
      dry or saline soil.

PMID- 22136664
TI  - Transcription regulation of abiotic stress responses in rice: a combined action
      of transcription factors and epigenetic mechanisms.
AB  - Plant growth and crop production are highly reduced by adverse environmental
      conditions and rice is particularly sensitive to abiotic stresses. Plants have
      developed a number of different mechanisms to respond and try to adapt to abiotic
      stress. Plant response to stress such as drought, cold, and high salinity,
      implies rapid and coordinated changes at transcriptional level of entire gene
      networks. During the last decade many transcription factors, belonging to
      different families, have been shown to act as positive or negative regulators of
      stress responsive genes, thus playing an extremely important role in stress
      signaling. More recently, epigenetic mechanisms have been also involved in the
      regulation of the stress responsive genes. In this review, we have performed a
      comprehensive analysis of the rice transcription factors reported so far as being
      involved in abiotic stress responses. The impact of abiotic stresses on
      epigenomes is also addressed. Finally, we update the connections made so far
      between DNA-binding transcription factors (TFs), and epigenetic mechanisms (DNA
      methylation and histones methylation or acetylation) emphasizing an integrative
      view of transcription regulation.

PMID- 22136665
TI  - Effect of chitosan coating enriched with thyme oil on postharvest quality and
      shelf life of shiitake mushroom (Lentinus edodes).
AB  - The effect of chitosan-oil coating on the postharvest quality and shelf life of
      shiitake (Lentinus edodes) mushrooms stored at 4 +/- 1  degrees C for 16 days was
      investigated. Mushroom weight loss, firmness, total phenolics, ascorbic acid,
      malondialdehyde (MDA), electrolyte leakage rate, and microbial and sensory
      quality were measured. The results indicate that treatment with chitosan-oil
      coating maintained tissue firmness, inhibited increase of respiration rate, and
      reduced microorganism counts, such as yeasts and molds and pseudomonad, compared
      to control treatment. The efficiency was better than that of thyme oil treatment
      or chitosan coating. Furthermore, shiitake mushrooms treated with chitosan-oil
      coating also exhibited significantly higher levels of total phenolics,
      flavonoids, as well as individual phenolic compounds than control. Sensory
      evaluation proved the efficacy of chitosan-oil coating by maintaining the overall
      quality of shiitake mushroom during the storage period. Our study suggests that
      chitosan-oil coating might be a promising candidate for maintaining shiitake
      mushroom quality and extending their postharvest life.

PMID- 22136666
TI  - Transforming growth factor beta receptor 1 is a new candidate prognostic
      biomarker after acute myocardial infarction.
AB  - BACKGROUND: Prediction of left ventricular (LV) remodeling after acute myocardial
      infarction (MI) is clinically important and would benefit from the discovery of
      new biomarkers. METHODS: Blood samples were obtained upon admission in patients
      with acute ST-elevation MI who underwent primary percutaneous coronary
      intervention. Messenger RNA was extracted from whole blood cells. LV function was
      evaluated by echocardiography at 4-months. RESULTS: In a test cohort of 32 MI
      patients, integrated analysis of microarrays with a network of protein-protein
      interactions identified subgroups of genes which predicted LV dysfunction
      (ejection fraction <= 40%) with areas under the receiver operating characteristic
      curve (AUC) above 0.80. Candidate genes included transforming growth factor beta
      receptor 1 (TGFBR1). In a validation cohort of 115 MI patients, TGBFR1 was up
      regulated in patients with LV dysfunction (P < 0.001) and was associated with LV
      function at 4-months (P = 0.003). TGFBR1 predicted LV function with an AUC of
      0.72, while peak levels of troponin T (TnT) provided an AUC of 0.64. Adding
      TGFBR1 to the prediction of TnT resulted in a net reclassification index of 8.2%.
      When added to a mixed clinical model including age, gender and time to
      reperfusion, TGFBR1 reclassified 17.7% of misclassified patients. TGFB1, the
      ligand of TGFBR1, was also up-regulated in patients with LV dysfunction (P =
      0.004), was associated with LV function (P = 0.006), and provided an AUC of 0.66.
      In the rat MI model induced by permanent coronary ligation, the TGFB1-TGFBR1 axis
      was activated in the heart and correlated with the extent of remodeling at 2
      months. CONCLUSIONS: We identified TGFBR1 as a new candidate prognostic biomarker
      after acute MI.

PMID- 22136668
TI  - Immunohistological pointers to a possible role for excessive cathelicidin (LL-37)
      expression by apocrine sweat glands in the pathogenesis of hidradenitis
      suppurativa/acne inversa.
AB  - BACKGROUND:   The cause of follicular occlusion, a key early event in the
      pathogenesis of hidradenitis suppurativa (HS), also known as acne inversa,
      remains unknown. OBJECTIVES: To identify changes, if any, in the antimicrobial
      peptide (AMP) and cytokine expression profile of HS affected human skin. METHODS:
      Quantitative immunohistomorphometry was used to compare the in situ protein
      expression of selected AMPs and cytokines in lesional HS skin from 18 patients
      with that in healthy skin (n = 12). The lesional skin from patients with HS was
      histologically subclassified based on the predominance of inflammation vs.
      scarring. RESULTS: Compared with healthy controls, significantly increased
      immunoreactivity for cathelicidin (LL-37) was noted in the apocrine sweat gland
      and distal outer root sheath (ORS) of the hair follicle (HF) epithelium in
      lesional HS skin. Immunoreactivity for LL-37, psoriasin, human beta-defensin 3
      (hBD3), alpha-melanocyte stimulating hormone (alpha-MSH), macrophage migration
      inhibitory factor (MIF), tumour necrosis factor (TNF)-alpha and interleukin (IL)
      8 was significantly increased in HS epidermis. LL-37 and TNF-alpha
      immunoreactivity was also increased in the dermis of lesional HS skin. In
      contrast, lysozyme expression was decreased in the epidermis of lesional HS skin,
      while that of TNF-alpha and IL-8 was decreased in the proximal ORS of HFs in HS
      lesions. These differences were most pronounced in HS with predominant
      inflammation. CONCLUSIONS:   Our observations raise the question as to whether
      excessive secretion of AMPs by the skin, in particular by the apocrine sweat
      glands, distal HF epithelium, and epidermis, may attract inflammation and thus
      facilitate or promote HS development.

PMID- 22136667
TI  - Cryptosporidium infection in a veal calf cohort in France: molecular
      characterization of species in a longitudinal study.
AB  - Feces from 142 animals were collected on 15 farms in the region of Brittany,
      France. Each sample was directly collected from the rectum of the animal and
      identified with the ear tag number. Animals were sampled three times, at 5, 15
      and 22 weeks of age. After DNA extraction from stool samples, nested PCR was
      performed to amplify partial 18S-rDNA and 60 kDa glycoprotein genes of
      Cryptosporidium. The parasite was detected on all farms. One hundred out of 142
      calves (70.4%) were found to be parasitized by Cryptosporidium. Amplified
      fragments were sequenced for Cryptosporidium species identification and revealed
      the presence of C. parvum (43.8%), C. ryanae (28.5%), and C. bovis (27%). One
      animal was infected with Cryptosporidium ubiquitum. The prevalence of these
      species was related to the age of the animal. C. parvum caused 86.7% of
      Cryptosporidium infections in 5-week-old calves but only 1.7% in 15-week-old
      animals. The analysis of the results showed that animals could be infected
      successively by C. parvum, C. ryanae, and C. bovis for the study period. C.
      parvum gp60 genotyping identifies 6 IIa subtypes of which 74.5% were represented
      by IIaA15G2R1. This work confirms previous studies in other countries showing
      that zoonotic C. parvum is the dominant species seen in young calves.

PMID- 22136669
TI  - Angiogenesis-related gene expression analysis in celiac disease.
AB  - Celiac disease (CD) involves disturbance of the small-bowel mucosal vascular
      network, and transglutaminase autoantibodies (TGA) have been related to
      angiogenesis disturbance, a complex phenomenon probably also influenced by common
      genetic variants in angiogenesis-related genes. A set of genes with
      "angiogenesis" GO term identified in a previous expression microarray experiment
      (SCG2, STAB1, TGFA, ANG, ERBB2, GNA13, PML, CASP8, ECGF1, JAG1, HIF1A, TNFSF13
      and TGM2) was selected for genetic and functional studies. SNPs that showed a
      trend for association with CD in the first GWAS were genotyped in 555 patients
      and 541 controls. Gene expression of all genes was quantified in 15 pairs of
      intestinal biopsies (diagnosis vs. GFD) and in three-dimensional HUVEC and T84
      cell cultures incubated with TGA-positive and negative serum. A regulatory SNP in
      TNFSF13 (rs11552708) is associated with CD (p = 0.01, OR = 0.7). Expression
      changes in biopsies pointed to TGM2 and PML as up-regulated antiangiogenic genes
      and to GNA13, TGFA, ERBB2 and SCG2 as down-regulated proangiogenic factors in CD.
      TGA seem to enhance TGM2 expression in both cell models, but PML expression was
      induced only in T84 enterocytes while GNA13 and ERBB2 were repressed in HUVEC
      endothelial cells, with several genes showing discordant effects in each model,
      highlighting the complexity of gene interactions in the pathogenesis of CD.
      Finally, cell culture models are useful tools to help dissect complex responses
      observed in human explants.

PMID- 22136670
TI  - Global assessment of experimental climate warming on tundra vegetation:
      heterogeneity over space and time.
AB  - Understanding the sensitivity of tundra vegetation to climate warming is critical
      to forecasting future biodiversity and vegetation feedbacks to climate. In situ
      warming experiments accelerate climate change on a small scale to forecast
      responses of local plant communities. Limitations of this approach include the
      apparent site-specificity of results and uncertainty about the power of short
      term studies to anticipate longer term change. We address these issues with a
      synthesis of 61 experimental warming studies, of up to 20 years duration, in
      tundra sites worldwide. The response of plant groups to warming often differed
      with ambient summer temperature, soil moisture and experimental duration. Shrubs
      increased with warming only where ambient temperature was high, whereas
      graminoids increased primarily in the coldest study sites. Linear increases in
      effect size over time were frequently observed. There was little indication of
      saturating or accelerating effects, as would be predicted if negative or positive
      vegetation feedbacks were common. These results indicate that tundra vegetation
      exhibits strong regional variation in response to warming, and that in vulnerable
      regions, cumulative effects of long-term warming on tundra vegetation - and
      associated ecosystem consequences - have the potential to be much greater than we
      have observed to date.

PMID- 22136671
TI  - Structural and physical properties of antibacterial Ag-doped nano-hydroxyapatite
      synthesized at 100 degrees C.
AB  - Synthesis of nanosized particle of Ag-doped hydroxyapatite with antibacterial
      properties is in the great interest in the development of new biomedical
      applications. In this article, we propose a method for synthesized the Ag-doped
      nanocrystalline hydroxyapatite. A silver-doped nanocrystalline hydroxyapatite was
      synthesized at 100 degrees C in deionized water. Other phase or impurities were
      not observed. Silver-doped hydroxyapatite nanoparticles (Ag:HAp) were performed
      by setting the atomic ratio of Ag/[Ag + Ca] at 20% and [Ca + Ag]/P as 1.67. The X
      ray diffraction studies demonstrate that powders made by co-precipitation at 100
      degrees C exhibit the apatite characteristics with good crystal structure and no
      new phase or impurity is found. The scanning electron microscopy (SEM)
      observations suggest that these materials present a little different morphology,
      which reveals a homogeneous aspect of the synthesized particles for all samples.
      The presence of calcium (Ca), phosphor (P), oxygen (O), and silver (Ag) in the
      Ag:HAp is confirmed by energy dispersive X-ray (EDAX) analysis. FT-IR and FT
      Raman spectroscopies revealed that the presence of the various vibrational modes
      corresponds to phosphates and hydroxyl groups. The strain of Staphylococcus
      aureus was used to evaluate the antibacterial activity of the Ca10
      xAgx(PO4)6(OH)2 (x = 0 and 0.2). In vitro bacterial adhesion study indicated a
      significant difference between HAp (x = 0) and Ag:HAp (x = 0.2). The Ag:Hap
      nanopowder showed higher inhibition.

PMID- 22136672
TI  - Identification of protein marker in vaginal wall tissues of women with stress
      urinary incontinence by protein chip array.
AB  - AIM: We sought to investigate protein biomarkers for stress urinary incontinence
      (SUI) in vaginal tissues using surface-enhanced laser desorption/ionization time
      of-flight mass spectrometry (SELDI-TOF MS) and examine if this is a reliable
      methodology to examine proteins in small tissue specimens. MATERIAL AND METHODS: 
      We compared protein expression profile of vaginal tissue from women with SUI and
      continent controls. A 22.6kDa peak was identified by subsequent weak cation
      exchange, reverse-phase fractionation, gel electrophoresis, and trypsin
      digestion, then analyzed by matrix assisted laser desorption/ionization mass
      spectrometry (MALDI MS) and MALDI MS-MS. Biomarker identity and expression level
      were confirmed by Western-blotting and immunohistochemistry. RESULTS: Expression
      of the 22.6kDa protein, identified as SM-22alpha, was significantly higher in
      women with SUI versus controls. A 3*3-mm tissue sample was sufficient for
      identification. Western-blot/immunohistochemistry confirmed the SELDI-TOS MS
      findings. CONCLUSION: SM-22alpha, a marker for myofibroblasts, was identified as
      a biomarker of SUI. Differential protein profiling by SELDI-TOF MS is a powerful
      and reliable tool for urogynecological research as it allows us to study an array
      of proteins simultaneously using small tissue samples.

PMID- 22136673
TI  - Foveal development in the premature infant: the motion picture.

PMID- 22136674
TI  - Inflammation after phakic implants.

PMID- 22136675
TI  - Corneal crosslinking and lens opacity.

PMID- 22136676
TI  - Myopic choroidal neovascularization.

PMID- 22136677
TI  - Late onset retinitis pigmentosa.

PMID- 22136679
TI  - Cataract and juvenile arthritis.

PMID- 22136680
TI  - Preoperative pupil size and LASIK.

PMID- 22136681
TI  - Holladay 2 formula.

PMID- 22136684
TI  - Lamellar keratoplasty.

PMID- 22136685
TI  - Visual function in glaucoma.

PMID- 22136686
TI  - Diabetic retinopathy and cardiovascular disease.

PMID- 22136689
TI  - Stem cell "tourism".

PMID- 22136690
TI  - Corneal collagen cross-linking.

PMID- 22136691
TI  - Herpetic blepharitis and inhaled budesonide.

PMID- 22136692
TI  - Rationale for the diabetic retinopathy clinical research network treatment
      protocol for center-involved diabetic macular edema.
AB  - OBJECTIVE: To describe the underlying principles used to develop a web-based
      algorithm that incorporated intravitreal anti-vascular endothelial growth factor
      (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy
      Clinical Research Network (DRCR.net) randomized clinical trial. DESIGN:
      Discussion of treatment protocol for DME. PARTICIPANTS: Subjects with vision loss
      resulting from DME involving the center of the macula. METHODS: The DRCR.net
      created an algorithm incorporating anti-VEGF injections in a comparative
      effectiveness randomized clinical trial evaluating intravitreal ranibizumab with
      prompt or deferred (>=24 weeks) focal/grid laser treatment in eyes with vision
      loss resulting from center-involved DME. Results confirmed that intravitreal
      ranibizumab with prompt or deferred laser provides superior visual acuity
      outcomes compared with prompt laser alone through at least 2 years. Duplication
      of this algorithm may not be practical for clinical practice. To share their
      opinion on how ophthalmologists might emulate the study protocol, participating
      DRCR.net investigators developed guidelines based on the algorithm's underlying
      rationale. MAIN OUTCOME MEASURES: Clinical guidelines based on a DRCR.net
      protocol. RESULTS: The treatment protocol required real-time feedback from a web
      based data entry system for intravitreal injections, focal/grid laser treatment,
      and follow-up intervals. Guidance from this system indicated whether treatment
      was required or given at investigator discretion and when follow-up should be
      scheduled. Clinical treatment guidelines, based on the underlying clinical
      rationale of the DRCR.net protocol, include repeating treatment monthly as long
      as there is improvement in edema compared with the previous month or until the
      retina is no longer thickened. If thickening recurs or worsens after
      discontinuing treatment, treatment is resumed. CONCLUSIONS: Duplication of the
      approach used in the DRCR.net randomized clinical trial to treat DME involving
      the center of the macula with intravitreal ranibizumab may not be practical in
      clinical practice, but likely can be emulated based on an understanding of the
      underlying rationale for the study protocol. Inherent differences between a web
      based treatment algorithm and a clinical approach may lead to differences in
      outcomes that are impossible to predict. The closer the clinical approach is to
      the algorithm used in the study, the more likely the outcomes will be similar to
      those published. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure
      may be found after the references.

PMID- 22136693
TI  - Recent advances in regulatory T cells.

PMID- 22136695
TI  - Recommendations on modern contact investigation methods for enhancing
      tuberculosis control.
AB  - Effective contact investigations are paramount to the success of tuberculosis
      (TB) control in high-risk communities in low TB prevalence countries. National
      and international guidelines on TB contact investigations are available and vary
      widely on recommendations. Because of the limitations  of traditional contact
      tracing, new approaches are under investigation, and in some cases in use, to
      ensure effective TB control in those persons and communities at greatest risk.
      These non-traditional approaches include the use of social network analysis,
      geographic information systems and  genomics, in addition to the widespread use
      of genotyping, to better understand TB transmission. Detailed guidelines for the
      use of these methods during TB outbreaks and in routine follow-up of TB contact
      investigations do not currently exist despite evidence that they may improve TB
      control  efforts. It remains unclear as to when it is most appropriate and
      effective to use a network-informed approach alone, or in combination with other
      methodologies as well as the extent of data collection required to inform
      practice. TB controllers should consider developing the capacity to facilitate 
      the systematic collection, analysis, and interpretation of contact investigation
      data using such novel methodologies, particularly in high-risk communities.
      Further investigation should focus on questionnaire development and adaptation,
      electronic data management and infrastructure, development  of local capability
      and consultant expertise, and the use of coordinated approaches, including
      deployment strategies and evaluation.

PMID- 22136694
TI  - Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells.
AB  - Mounting an efficient immune response to pathogens while avoiding damage to host
      tissues is the central task of the immune system. Emerging evidence has
      highlighted the contribution of the CD8(+) lineage of regulatory T cells to the
      maintenance of self-tolerance. Specific recognition of the MHC class Ib molecule
      Qa-1 complexed to peptides expressed by activated CD4(+) T cells by regulatory
      CD8(+) T cells triggers an inhibitory interaction that prevents autoimmune
      responses. Conversely, defective Qa-1-restricted CD8(+) regulatory activity can
      result in development of systemic autoimmune disease. Here, we review recent
      research into the cellular and molecular basis of these regulatory T cells, their
      mechanism of suppressive activity and the potential application of these insights
      into new treatments for autoimmune disease and cancer.

PMID- 22136696
TI  - Combined process automation for large-scale EEG analysis.
AB  - Epileptogenesis is a dynamic process producing increased seizure susceptibility.
      Electroencephalography (EEG) data provides information critical in understanding
      the evolution of epileptiform changes throughout epileptic foci. We designed an
      algorithm to facilitate efficient large-scale EEG analysis via linked automation
      of multiple data processing steps. Using EEG recordings obtained from electrical
      stimulation studies, the following steps of EEG analysis were automated: (1)
      alignment and isolation of pre- and post-stimulation intervals, (2) generation of
      user-defined band frequency waveforms, (3) spike-sorting, (4) quantification of
      spike and burst data and (5) power spectral density analysis. This algorithm
      allows for quicker, more efficient EEG analysis.

PMID- 22136697
TI  - Modeling porous scaffold microstructure by a reaction-diffusion system and its
      degradation by hydrolysis.
AB  - One of the most important areas of Tissue Engineering is the research about bone
      regeneration and the replacement of its function. To meet this requirement,
      scaffolds have been developed to allow the cell migration, the growth of bone
      tissue, the transport of growth factors and nutrients and the renovation of the
      mechanical properties of bone. Scaffolds are made of different biomaterials and
      manufactured using various techniques that, in some cases, do not allow full
      control over the size and orientation of the pores that characterize the scaffold
      microstructure. From this perspective, we propose a novel hypothesis that a
      reaction-diffusion system can be used to design the geometrical specifications of
      the bone matrix. The validation of this hypothesis is performed by simulations of
      the reaction-diffusion system in a representative tridimensional unit cell,
      coupled with a model of scaffold degradation by hydrolysis. The results show the
      possibility that a Reaction-Diffusion system can control features such as the
      percentage of porosity, trabecular size, orientation, and interconnectivity of
      pores.

PMID- 22136698
TI  - Identifying an effective way to communicate with homeless populations.

PMID- 22136699
TI  - Using Trust databases to identify predictors of late booking for antenatal care
      within the UK.
AB  - OBJECTIVES: To identify predictors of late booking for antenatal care using
      routinely collected data. STUDY DESIGN: Retrospective cohort study. METHODS:
      Variables were selected with reference to comprehensive literature review. Data
      were extracted from a London hospital case-note database, and predictors of late
      booking were identified using logistic regression. RESULTS: In total, 5629 women
      were included in the study. Median gestation at booking was 14 weeks, and 31% of
      women booked after 18 weeks of gestation. Variables with insufficient data
      recorded included language abilities, nationality and social risk. Women aged
      between 15 and 19 years, women with more than four children, and women belonging
      to the ethnic group 'other' were all significantly more likely to book late.
      Women with a body mass index >=30kg/m(2) were 1.5 times more likely to book late
      (not significant). CONCLUSION: Case-note databases are a potentially easy and
      effective way to analyse access to care and provider compliance with quality
      standards. Current deficits in routine data collection need to be addressed
      urgently in order to make this possible.

PMID- 22136700
TI  - Unusual epidemic events: a new method of early orientation and differentiation
      between natural and deliberate epidemics.
AB  - OBJECTIVE: To develop a model for quick and accurate evaluation of unusual
      epidemic events (UEE), based on the original model of bioterrorism risk
      assessment. METHODS: A new scoring system was developed for quick differentiation
      between a biological attack and other epidemics, using eight qualitative and six
      quantitative indicators. RESULTS: A new scoring system was applied to three UEEs:
      (1) a spontaneous outbreak of a new or re-emerging disease ('swine flu'); (2) a
      spontaneous outbreak following accidental release of a pathogen (Sverdlovsk
      anthrax); and (3) a spontaneous natural outbreak of a known endemic disease that
      may mimic bioterrorism or biowarfare (Kosovo tularaemia). The disease agent was
      found to be the most important and the most informative UEE component of the
      scoring system. CONCLUSIONS: This new scoring system may be useful for public
      health institutions and federal civil and military officials responsible for bio
      attack investigations.

PMID- 22136701
TI  - Taloside inhibitors of galectin-1 and galectin-3.
AB  - Galectin-1 and galectin-3 have roles in cancer and inflammation. Galectin-1 has
      recently emerged as a significant protein produced by tumour cells to promote
      tumour development, angiogenesis and metastasis and consequently represents an
      important target to inhibit. The design of inhibitors targeting the carbohydrate
      recognition domain that is known to recognize galactose is an important approach
      in the fight against cancer. Based on the analysis of crystal structures, we
      pursued the concept that if the galactose was replaced with talose (the C2 epimer
      of galactose) as a scaffold, then O2 substituents would be directed closer to the
      protein surface and provide opportunity to design inhibitors that are more
      specific towards particular galectins. Our elucidation of X-ray crystal
      structures of two of our synthesized talosides in complex with galectin-1 and
      galectin-3 provides the first atomic information on the interactions of
      galectins, and indeed any protein, with talosides. These results have enabled a
      structure-based rationale for the specificity differences shown by galectin-1 and
      galectin-3 towards these talosides and demonstrate new opportunities for further
      exploitation as specific inhibitors of galectins.

PMID- 22136702
TI  - Health care providers involved in end-of-life care. Foreword.

PMID- 22136703
TI  - The history of hospice and palliative care.

PMID- 22136704
TI  - Vital communication skills at the end of life.

PMID- 22136705
TI  - Pain management principles.

PMID- 22136706
TI  - Too much, too little, or just the right amount: finding the balance in palliative
      radiotherapy.

PMID- 22136707
TI  - Establishing communication within the field of pediatric oncology: a palliative
      care approach.

PMID- 22136708
TI  - Palliative care nursing.

PMID- 22136709
TI  - Oncology social work in palliative care.

PMID- 22136710
TI  - Spiritual care for palliative patients.

PMID- 22136711
TI  - Oxidised fish oil does not influence established markers of oxidative stress in
      healthy human subjects: a randomised controlled trial.
AB  - Intake of fish oil reduces the risk of CHD and CHD deaths. Marine n-3 fatty acids
      (FA) are susceptible to oxidation, but to our knowledge, the health effects of
      intake of oxidised fish oil have not previously been investigated in human
      subjects. The aim of the present study was to investigate markers of oxidative
      stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after
      intake of oxidised fish oil. In a double-blinded randomised controlled study,
      healthy subjects (aged 18-50 years, n 54) were assigned into one of three groups
      receiving capsules containing either 8 g/d of fish oil (1.6 g/d EPA+DHA; n 17), 8
      g/d of oxidised fish oil (1.6 g/d EPA+DHA; n 18) or 8 g/d of high-oleic sunflower
      oil (n 19). Fasting blood and morning spot urine samples were collected at weeks
      0, 3 and 7. No significant changes between the different groups were observed
      with regard to urinary 8-iso-PGF2alpha; plasma levels of 4-hydroxy-2-hexenal, 4
      hydroxy-2-nonenal and alpha-tocopherol; serum high sensitive C-reactive protein;
      or activity of antioxidant enzymes in erythrocytes. A significant increase in
      plasma level of EPA+DHA was observed in both fish oil groups, but no significant
      difference was observed between the fish oil groups. No changes in a variety of
      in vivo markers of oxidative stress, lipid peroxidation or inflammation were
      observed after daily intake of oxidised fish oil for 3 or 7 weeks, indicating
      that intake of oxidised fish oil may not have unfavourable short-term effects in
      healthy human subjects.

PMID- 22136712
TI  - Biocleavable comb-shaped gene carriers from dextran backbones with bioreducible
      ATRP initiation sites.
AB  - It is of crucial importance to design reduction-sensitive polysaccharide-based
      copolymers for intracellular triggered gene and drug delivery. In this work, a
      simple two-step method involving the reaction of hydroxyl groups of dextran with
      cystamine was first developed to introduce reduction-sensitive disulfide linked
      initiation sites of atom transfer radical polymerization (ATRP) onto dextran.
      Well-defined biocleavable comb-shaped vectors consisting of nonionic dextran
      backbones and disulfide-linked cationic P(DMAEMA) side chains were subsequently
      prepared via ATRP for highly efficient gene delivery. The P(DMAEMA) side chains
      can be readily cleavable from the dextran backbones under reducible conditions.
      Moreover, the bioreducible P(DMAEMA) side chains can be functionalized by
      poly(poly(ethylene glycol)ethyl ether methacrylate) (P(PEGEEMA)) end blocks to
      reduce the cytotoxicity and further enhance the gene transfection efficiency.
      This present study demonstrated that properly grafting short bioreducible
      polycation side chains from a nonionic polysaccharide backbone with biocleavable
      ATRP initiation sites is an effective means to produce a class of polysaccharide
      based gene delivery vectors.

PMID- 22136713
TI  - 3D co-culture of hematopoietic stem and progenitor cells and mesenchymal stem
      cells in collagen scaffolds as a model of the hematopoietic niche.
AB  - Here, we propose a collagen-based three-dimensional (3D) environment for
      hematopoietic stem and progenitor cells (HPC) with mesenchymal stem cells (MSC)
      derived either from bone marrow (BM) or umbilical cord (UC), to recapitulate the
      main components of the BM niche. Mechanisms described for HPC homeostasis were
      systematically analyzed in comparison to the conventional liquid HPC culture. The
      3D-cultivation allows dissecting two sub-populations of HPC: (I) HPC in
      suspension above the collagen gel and (II) migratory HPC in the collagen fibres
      of the collagen gel. The different sites represent distinct microenvironments
      with significant impact on HPC fate. HPC in niche I (suspension) are
      proliferative and a dynamic culture containing HPC (CD34(+)/CD38(-)), maturing
      myeloid cells (CD38(+), CD13(+), CAE(+)) and natural killer (NK) cells (CD56(+)).
      In contrast, HPC in niche II showed clonal growth with significant high levels of
      the primitive CD34(+)/CD38(-) phenotype with starting myeloid (CD13(+), CAE(+))
      differentiation, resembling the endosteal part of the BM niche. In contrast, UC
      MSC are not adequate for HSC expansion as they significantly enhance HPC
      proliferation and lineage commitment. In conclusion, the 3D-culture system using
      collagen and BM-MSC enables HPC expansion and provides a potential platform to
      dissect regulatory mechanisms in hematopoiesis.

PMID- 22136714
TI  - Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant
      breast cancer and inhibiting invasive metastases of melanoma.
AB  - Multidrug resistance and cancer metastases are two obstacles to a successful
      chemotherapy and metastases are closely associated with drug resistance.
      Mitochondrial targeting topotecan-loaded liposomes have been developed to
      overcome this resistance and resistance-related metastases. Investigations were
      performed on breast cancer MCF-7 and resistant MCF-7/adr cells, MCF-7 and
      resistant MCF-7/adr tumor spheroids, resistant MCF-7/adr cell xenografts in nude
      mice, and a naturally resistant B16 melanoma metastatic model in nude mice. The
      mitochondrial targeting topotecan-loaded liposomes were approximately 64 nm in
      size, and exhibited the strongest inhibitory effects on MCF-7 cells and resistant
      MCF-7/adr cells. Mitochondrial targeting effects were demonstrated by co
      localization in mitochondria, enhanced drug content in mitochondria, dissipated
      mitochondrial membrane potential, opening of mitochondrial permeability
      transition pores, release of cytochrome C, and activation of caspase 9 and 3. The
      targeting liposomes had a stronger inhibitory effect on the resistant tumor
      spheroids in vitro, enhanced accumulation in resistant MCF-7/adr cell xenografts
      in mice, as well as being very effective on resistant MCF-7/adr cell xenografts
      in mice, and having a marked anti-metastastic effect on the naturally resistant
      B16 melanoma metastatic model in mice. In conclusion, mitochondrial targeting
      topotecan-loaded liposomes could be a promising strategy for treating resistant
      cancers and resistance-related metastases.

PMID- 22136716
TI  - Inducing functional radial glia-like progenitors from cortical astrocyte cultures
      using micropatterned PMMA.
AB  - Radial glia cells (RGC) are multipotent progenitors that generate neurons and
      glia during CNS development, and which also served as substrate for neuronal
      migration. After a lesion, reactive glia are the main contributor to CNS
      regenerative blockage, although some reactive astrocytes are also able to de
      differentiate in situ into radial glia-like cells (RGLC), providing beneficial
      effects in terms of CNS recovery. Thus, the identification of substrate
      properties that potentiate the ability of astrocytes to transform into RGLC in
      response to a lesion might help in the development of implantable devices that
      improve endogenous CNS regeneration. Here we demonstrate that functional RGLC can
      be induced from in vitro matured astrocytes by using a precisely-sized
      micropatterned PMMA grooved scaffold, without added soluble or substrate adsorbed
      biochemical factors. RGLC were extremely organized and aligned on 2 MUm line
      patterned PMMA and, like their embryonic counterparts, express nestin, the neuron
      glial progenitor marker Pax6, and also proliferate, generate different
      intermediate progenitors and support and direct axonal growth and neuronal
      migration. Our results suggest that the introduction of line patterns in the size
      range of the RGC processes in implantable scaffolds might mimic the topography of
      the embryonic neural stem cell niche, driving endogenous astrocytes into an RGLC
      phenotype, and thus favoring the regenerative response in situ.

PMID- 22136715
TI  - Predicting biomaterial property-dendritic cell phenotype relationships from the
      multivariate analysis of responses to polymethacrylates.
AB  - Dendritic cells (DCs) play a critical role in orchestrating the host responses to
      a wide variety of foreign antigens and are essential in maintaining immune
      tolerance. Distinct biomaterials have been shown to differentially affect the
      phenotype of DCs, which suggested that biomaterials may be used to modulate
      immune response toward the biologic component in combination products. The
      elucidation of biomaterial property-DC phenotype relationships is expected to
      inform rational design of immuno-modulatory biomaterials. In this study, DC
      response to a set of 12 polymethacrylates (pMAs) was assessed in terms of surface
      marker expression and cytokine profile. Principal component analysis (PCA)
      determined that surface carbon correlated with enhanced DC maturation, while
      surface oxygen was associated with an immature DC phenotype. Partial square
      linear regression, a multivariate modeling approach, was implemented and
      successfully predicted biomaterial-induced DC phenotype in terms of surface
      marker expression from biomaterial properties with R(prediction)(2) = 0.76.
      Furthermore, prediction of DC phenotype was effective based on only theoretical
      chemical composition of the bulk polymers with R(prediction)(2) = 0.80. These
      results demonstrated that immune cell response can be predicted from biomaterial
      properties, and computational models will expedite future biomaterial design and
      selection.

PMID- 22136717
TI  - The effect of collagen-binding vascular endothelial growth factor on the
      remodeling of scarred rat uterus following full-thickness injury.
AB  - Serious injuries of uterine which lead to scar formation will finally result in
      infertility or pregnancy complications. There are few effective methods to treat
      such damages because of the shortage of native tissues. Vascular endothelial
      growth factor (VEGF) is important for the formation of new vessels and re
      epithelialization of endometrium. Here we produced a collagen-binding VEGF by
      fusing a collagen-binding domain to the N-terminal of native VEGF. After
      injection into a rat scarred uterus model (partial of rat uterine horn was
      excised and left for scar formation) the collagen targeting VEGF promoted
      remodeling of the scarred uterus including the regeneration of endometrium,
      muscular cells, and vascularization and improved pregnancy outcomes. Thus,
      collagen-binding VEGF may be a pragmatic solution for the treatment of severe
      uterine damages.

PMID- 22136718
TI  - Cardiac tissue engineering using tissue printing technology and human cardiac
      progenitor cells.
AB  - Tissue engineering is emerging as a potential therapeutic approach to overcome
      limitations of cell therapy, like cell retention and survival, as well as to
      mechanically support the ventricular wall and thereby prevent dilation. Tissue
      printing technology (TP) offers the possibility to deliver, in a defined and
      organized manner, scaffolding materials and living cells. The aim of our study
      was to evaluate the combination of TP, human cardiac-derived cardiomyocyte
      progenitor cells (hCMPCs) and biomaterials to obtain a construct with cardiogenic
      potential for in vitro use or in vivo application. With this approach, we were
      able to generate an in vitro tissue with homogenous distribution of cells in the
      scaffold. Cell viability was determined after printing and showed that 92% and
      89% of cells were viable at 1 and 7 days of culturing, respectively. Moreover, we
      demonstrated that printed hCMPCs retained their commitment for the cardiac
      lineage. In particular, we showed that 3D culture enhanced gene expression of the
      early cardiac transcription factors Nkx2.5, Gata-4 and Mef-2c as well as the
      sarcomeric protein TroponinT. Printed cells were also able to migrate from the
      alginate matrix and colonize a matrigel layer, thereby forming tubular-like
      structures. This indicated that printing can be used for defined cell delivery,
      while retaining functional properties.

PMID- 22136719
TI  - The involvement of integrin beta1 signaling in the migration and myofibroblastic
      differentiation of skin fibroblasts on anisotropic collagen-containing
      nanofibers.
AB  - Utilization of nanofibrous matrices for skin wound repair holds great promise due
      to their morphological and dimensional similarity to native extracellular matrix
      (ECM). It becomes highly desired to understand how various nanofibrous matrices
      regulate skin cell behaviors and intracellular signaling pathways, important to
      tuning the functionality of tissue-engineered skin grafts and affecting the wound
      healing process. In this study, the phenotypic expressions of normal human dermal
      fibroblasts (NHDFs) on collagen-containing nanofibrous matrices with either
      isotropic (i.e., fibers collected randomly with no alignment) or anisotropic
      (i.e., fibers collected with alignment) fiber organizations were studied by
      immunostaining, migration assay and molecular analyses. Results showed that both
      nanofibrous matrices supported the attachment and growth of NHDFs similarly,
      while showing different cell morphology with distinct variation in focal adhesion
      formation and distribution. Anisotropic nanofibers significantly triggered the
      integrin beta1 signaling pathway in NHDFs as evidenced by an increase of active
      integrin beta1 (130 kD mature form) and phosphorylation of focal adhesion kinase
      (FAK) at Tyr-397. Anisotropic matrices also promoted the migration of NHDFs along
      the fibers, while neutralization of the integrin beta1 activity abolished this
      promotion. Moreover, the fibroblast-to-myofibroblast differentiation was greatly
      enhanced for the NHDFs cultured on anisotropic nanofibrous matrices over a period
      of 48 h. Inhibition of cellular integrin beta1 activity by neutralizing antibody
      eliminated this enhancement. These findings suggest the important role of
      integrin beta1 signaling pathway in regulating the nanofiber-induced fibroblast
      phenotypic alteration and providing insightful understanding of the possible
      application of collagen-containing nanofibrous matrices for skin regeneration.

PMID- 22136720
TI  - Predicting protein instability in sustained protein delivery systems using
      spectral-phase interference.
AB  - Biodegradable and non-biodegradable polymers represent promising materials for
      sustained protein delivery systems. However, structural protein instabilities due
      to interactions with the polymer surface are often observed. Aim of the present
      study was to analyze and predict these instabilities by determination of
      adsorption pattern and extent via biomolecular interaction analysis. A new
      optical method based on spectral-phase interference successfully demonstrated its
      suitability for this new application scope. It was characterized in terms of
      sensitivity, reproducibility and dynamic range using bovine serum albumin (BSA)
      as model compound. For protein-polymer interaction studies, materials with
      different wettabilities and zeta potential were selected and successfully applied
      on the sensor chip: Glass, poly(styrene), poly(lactic acid), poly(lactic-co
      glycolic acid), and poly(ethylene carbonate). Concentration dependent adsorption
      curves revealed two principal adsorption patterns based on the connection between
      BSA spreading and supply rate. This connection was stronger influenced by polymer
      hydrophobicity than surface charge. Association, dissociation and binding rate
      constants in the range from 0.15 to 34.19 * 10(-6) M were obtained. Atomic force
      microscopy images of the films before and after adsorption confirmed the previous
      elaborated model. Poly(ethylene carbonate) emerged as highly promising
      biomaterial for protein delivery due to its favorable adsorption behavior based
      on low polymer-protein interactions.

PMID- 22136721
TI  - Successful use of acarbose to manage post-prandial glycaemia in two patients with
      type 1 diabetes on continuous subcutaneous insulin infusion.
AB  - Post-prandial hyperglycaemia is a particular problem for some patients with
      diabetes despite administering continuous subcutaneous insulin infusion (CSII) to
      deliver insulin flexibly. We describe two cases of patients on CSII with
      persistent post-prandial hyperglycaemia despite varying insulin doses and timing.
      Treatment with acarbose improved their glycaemic control.

PMID- 22136722
TI  - Insulin analogues and severe hypoglycaemia in type 1 diabetes.
AB  - INTRODUCTION: The effect of insulin analogues on glycaemic control is well
      documented, whereas the effect on avoidance of severe hypoglycaemia remains
      tentative. We studied the frequency of severe hypoglycaemia in unselected
      patients with type 1 diabetes treated with insulin analogues, human insulin, or
      mixed regimens. METHODS: A questionnaire was posted from six Danish diabetes
      clinics to 6112 unselected patients with type 1 diabetes and filled in by 3861
      patients (63.2%). Primary endpoint was number of episodes of severe hypoglycaemia
      in the preceding year. Mild hypoglycaemia was also reported. RESULTS: The
      frequency of severe hypoglycaemic episodes per patient-year in patients receiving
      long-acting insulin analogues was 1.47+/-0.18 versus 1.09+/-0.10 in patients on
      long-acting human insulin (p=0.01). The frequency of severe hypoglycaemic
      episodes per patient-year was 1.09+/-0.11 in patients on short-acting insulin
      analogues versus 1.26+/-0.13 in patients on short-acting human insulin (p=0.15),
      which was statistically significant in an adjusted analysis. CONCLUSIONS: Severe
      hypoglycaemia is more frequent in patients with type 1 diabetes treated with long
      acting insulin analogues. Confounding by indication may be involved. Clinical
      intervention trials using insulin analogues in patients prone to severe
      hypoglycaemia are highly needed.

PMID- 22136723
TI  - Open-label study of the efficacy and safety of topical treatment with TDT 067
      (terbinafine in Transfersome(r)) in patients with onychomycosis.

PMID- 22136724
TI  - Serum cholesterol levels and survival after rtPA treatment in acute stroke.
AB  - BACKGROUND: According to the reverse epidemiology hypothesis, high cholesterol
      levels might be protective and associated with greater survival rates under
      certain conditions. In stroke patients, a clear correlation between lipid levels
      and mortality after ischaemic and hemorrhagic strokes has been demonstrated. The
      aim of this study was to analyze the impact of lipid levels on 3-month mortality
      in patients with ischaemic stroke (IS) homogeneously treated with intravenous
      rtPA and admitted to a monitored acute stroke unit. METHODS: Retrospective
      analysis of a prospective cohort of 220 patients with an IS treated with rtPA
      within the first 4.5 h in a single tertiary hospital from January 2005 to August
      2010. RESULTS: Mortality at 3 months was 15.0%. Univariate analysis showed that
      age, NIHSS at admission, heart failure, and atrial fibrillation were directly
      related to 3-month mortality; cholesterol, triglycerides, and low density
      lipoprotein were inversely associated. The death rate by cholesterol level was
      5.5% for the highest tertile (>192 mg/dl), 13.7% for the middle (192-155 mg/dl),
      and 25.7% for the lowest (<155 mg/dl), P = 0.003. Multivariate analysis showed
      that amongst the lipid determinations, only cholesterol [OR: 0.985 (95% CI: 0.972
      0.998), P = 0.021] was inversely associated with 3-month mortality. The
      'protective' effect of cholesterol was independent of stroke severity and
      remained significant in non-lacunar strokes. CONCLUSIONS: Survival of stroke
      patients receiving current, most effective medical treatment is related to blood
      cholesterol levels, with an inverse relationship between cholesterol and
      mortality. The mechanism of this apparently paradoxical situation remains
      unexplained but merits further research.

PMID- 22136725
TI  - Ovarian responses in Bos indicus heifers treated to synchronise ovulation with
      intravaginal progesterone releasing devices, oestradiol benzoate, prostaglandin
      F(2alpha) and equine chorionic gonadotrophin.
AB  - The objectives were: (i) improve understanding of the ovarian responses of Bos
      indicus heifers treated with different ovulation synchronisation protocols, (ii)
      compare ovarian responses of B. indicus heifers treated with intravaginal
      progesterone releasing device (IPRD)+oestradiol benzoate (ODB) versus a
      conventional prostaglandin F(2alpha) (PGF(2alpha)) protocol and (iii) investigate
      whether reducing the amount of progesterone (P(4)) in the IPRD, and treatment
      with equine chorionic gonadotrophin (eCG) would increase the proportion of
      heifers with normal ovarian function during the synchronised and return cycles.
      Two-year-old Brahman (n=30) and Brahman-cross (n=34) heifers were randomly
      allocated to three IPRD-treatment groups: (i) standard-dose IPRD (Cue-Mate((r))
      1.56g P(4); n=17); (ii) half-dose IPRD (Cue-Mate((r)) 0.78g P(4); n=15); (iii)
      half-dose IPRD+300IU eCG at IPRD removal (n=14), and a non-IPRD control group
      (iv) 2*PGF(2alpha) (500MUg cloprostenol) on Days -16 and -2 (n=18). IPRD-treated
      heifers received 250MUg cloprostenol at IPRD insertion (Day -10) and IPRD removal
      (Day -2) and 1mg ODB on Days -10 and -1. Ovarian function was evaluated by
      ultrasonography and plasma P(4) throughout the synchronised and return cycles.
      The mean diameter of the dominant follicle observed at 54-56h after IPRD removal,
      was greater for heifers which ovulated than heifers which did not ovulate
      (P<0.001; 14.5+/-1.1 vs. 9.3+/-0.6mm, respectively). The prevalence of IPRD
      treated heifers with ovarian dysfunction (persistent CL, failure to re-ovulate,
      shortened luteal phase) was 39%. This relatively high prevalence of ovarian
      dysfunction may explain the commonly reported, lower than expected pregnancy
      rates to FTAI in B. indicus heifers treated to synchronise ovulation.

PMID- 22136726
TI  - Lactoferrin, a key molecule in immune and inflammatory processes.
AB  - Lactoferrin (Lf) belongs to the family of antimicrobial molecules that constitute
      the principal defense line of nonvertebrate organisms. In human immunity, their
      roles are considerably extended, and actually exceed mere direct antimicrobial
      properties. As a result, Lf is involved in both innate and adaptive immunities
      where its modulating effects not only help the host fight against microbes but
      also protect the host against harmful effects of inflammation. Such beneficial
      effects have been noticed in studies using dietary Lf, without the experimenters
      always explaining the exact modes of action of Lf. Effects on mucosal and
      systemic immunities are indeed often observed, which make the roles of Lf tricky
      to decipher. It is now known that the immunomodulatory properties of Lf are due
      to its ability to interact with numerous cellular and molecular targets. At the
      cellular level, Lf modulates the migration, maturation, and functions of immune
      cells. At the molecular level, in addition to iron binding, interactions of Lf
      with a plethora of compounds, either soluble or cell-surface molecules, account
      for its modulatory properties. This paper reviews our current understanding of
      the mechanisms that explain the regulatory properties of Lf in immune and
      inflammatory processes.

PMID- 22136727
TI  - Sialidases play a key role in infection and anaemia in Trypanosoma congolense
      animal trypanosomiasis.
AB  - Animal African trypanosomiasis is a major constraint to livestock productivity
      and has an important impact on millions of people in developing African
      countries. This parasitic disease, caused mainly by Trypanosoma congolense,
      results in severe anaemia leading to animal death. In order to characterize
      potential targets for an anti-disease vaccine, we investigated a multigenic trans
      sialidase family (TcoTS) in T. congolense. Sialidase and trans-sialidase
      activities were quantified for the first time, as well as the tightly regulated
      TcoTS expression pattern throughout the life cycle. Active enzymes were expressed
      in bloodstream form parasites and released into the blood during infection. Using
      genetic tools, we demonstrated a significant correlation between TcoTS silencing
      and impairment of virulence during experimental infection with T. congolense.
      Reduced TcoTS expression affected infectivity, parasitaemia and pathogenesis
      development. Immunization-challenge experiments using recombinant TcoTS
      highlighted their potential protective use in an anti-disease vaccine.

PMID- 22136728
TI  - Intestinal infection following aerosol challenge of calves with Mycobacterium
      avium subspecies paratuberculosis.
AB  - A challenge experiment was performed to investigate whether administration of
      Mycobacterium avium subsp. paratuberculosis (MAP) via the respiratory route leads
      to MAP infection in calves. Eighteen calves from test negative dams were randomly
      allocated to four groups. Six calves were challenged with MAP nasally and six
      calves were challenged by transtracheal injection; three orally challenged calves
      served as positive controls, and three non challenged calves as negative
      controls. The challenge was performed as a nine-fold trickle dose, 10(7) CFU in
      total. Blood and faecal samples were collected frequently. Calves were euthanized
      three months post-challenge and extensively sampled. Blood samples were tested
      for the presence of antibodies and interferon gamma producing cells by ELISA.
      Faecal and tissue samples were cultured in a liquid culture system and the
      presence of MAP was confirmed by IS900 realtime PCR. Fourteen out of fifteen
      calves had no MAP antibody response. The negative controls remained negative; all
      positive controls became infected. Two nasally challenged calves showed a
      Purified Protein Derivative Avian (PPDA) specific interferon gamma response. In
      all nasally challenged calves, MAP positive intestinal samples were detected. In
      three calves of the nasal group MAP positive retropharyngeal lymph nodes or
      tonsils were detected. In all calves of the transtracheal group MAP positive
      intestinal tissues were detected as well and three had a MAP positive
      tracheobronchial lymph node. These findings indicate that inhalation of MAP
      aerosols can result in infection. These experimental results may be relevant for
      transmission under field conditions since viable MAP has been detected in dust on
      commercial dairy farms.

PMID- 22136729
TI  - Commentary on "The modifying effect of Xmn1-HBG2 on thalassemic phenotype is
      associated with its linked elements in the beta globin locus control region,
      including the palindromic site at 5' HS4" by M. Neishabury et al.

PMID- 22136730
TI  - Alteration of HGF and TSP-1 expression in ovarian carcinoma associated with
      clinical features.
AB  - AIM: The aim of this study was to investigate the expression levels of hepatocyte
      growth factor (HGF) and thrombospondin-1 (TSP-1) with the clinical pathological
      factors in ovarian cancer, and the correlation between HGF and TSP-1 expression
      at the protein level. MATERIAL AND METHODS: Immunohistochemistry was applied to
      detect the location and expression of HGF and TSP-1 protein in ovarian cancer and
      benign ovarian tumor tissue. Real-time quantitative polymerase chain reaction was
      applied to detect HGF and TSP-1 gene mRNA expression in ovarian cancer and benign
      ovarian tumor tissue. RESULTS: The level and positive expression rate of HGF mRNA
      in ovarian cancer tissue was significantly higher than in ovarian adenoma
      tissues. The positive expression of HGF protein in ovarian cancer was related
      with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph
      node metastasis. The level and positive expression rate of TSP-1 mRNA in ovarian
      cancer tissue was lower than in ovarian adenoma. The absence expression of TSP-1
      protein in ovarian cancer was significantly related with FIGO stage and
      histological grade. The intensity of these positive expressions in ovarian cancer
      tissues were significant negatively associated with each other. CONCLUSION:
      Abnormal expression of HGF and TSP-1 may be related to malignant progression of
      ovarian cancer and associated in the pathogenesis of ovarian cancer.

PMID- 22136731
TI  - Coagulation factor VII R353Q polymorphism and the risk of puerperal cerebral
      venous thrombosis.
AB  - Puerperal cerebral venous thrombosis (CVT) is a relatively common form of stroke
      in young women in India. The blood coagulation factor VII (FVII) R353Q
      polymorphism increases the risk for venous thrombosis. Our aim was to investigate
      the association of FVII R353Q polymorphism with the risk of puerperal CVT. A
      total of 100 women with puerperal CVT and 102 age-matched women without
      postpartum complications were investigated. FVII R353Q genotypes were identified
      using restriction fragment length polymorphism analysis. Our results showed that
      the homozygous FVII 353QQ genotype was present in 9% and 8% of patients and
      controls, respectively; and 42% of patients and 31.4% of controls had the
      heterozygous 353RQ genotype (odds ratio = 1.55, 95% confidence interval = 0.89
      2.70; p = 0.243). Our findings suggest that the FVII R353Q polymorphism is not
      associated with increased risk for CVT occurring during the puerperal period in
      Indian women.

PMID- 22136732
TI  - Prognostic value of intra-operative abnormal muscle response monitoring during
      microvascular decompression for long-term outcome of hemifacial spasm.
AB  - The reliability of intra-operative abnormal muscle response (AMR) monitoring as
      an indicator of post-operative outcome in patients with hemifacial spasm (HFS) is
      under debate. The primary aim of this study was to evaluate the correlation
      between intra-operative AMR changes and long-term post-operative outcome. We
      monitored intra-operative AMR during microvascular decompression (MVD) in
      consecutive patients with HFS (n = 104). Patients in this study were divided into
      two groups based on whether their AMR disappeared or persisted following MVD.
      Ninety patients were followed-up, and the mean duration from surgery to final
      follow-up examination was 3.7 years. Fourteen patients were lost to follow-up.
      AMR disappeared during surgery for 80 patients; of these, 74 achieved complete
      resolution of HFS, five had persistent HFS, and one patient developed a
      recurrence of HFS. Of the 10 patients with persistent AMR despite effective MVD,
      eight patients achieved complete resolution, one patient had persistent HFS, and
      one developed recurrent HFS. The long-term clinical outcome of HFS after MVD did
      not significantly correlate with intra-operative AMR changes (p = 0.791).
      Therefore, we suggest that intra-operative AMR monitoring may not be a reliable
      indicator of long-term post-operative outcome for HFS.

PMID- 22136733
TI  - Recanalization with stent-based mechanical thrombectomy in anterior circulation
      major ischemic stroke.
AB  - We report the use of a self-expanding stent as a thrombectomy device in 17
      patients (mean age 64.3 years) with major ischemic stroke secondary to large
      vessel occlusion. The patients had a mean National Institutes of Health Stroke
      Scale (NIHSS) score of >12, no cerebral hemorrhage or early infarction signs that
      affected more than 1/3 of the endangered territory, and an insufficient
      collateral supply. Within 8 hours of symptom onset, a stent (Solitaire; ev3,
      Irvine, CA, USA) was deployed across the occluded segment (endovascular bypass
      step). A repeat angiogram was performed to evaluate reconstituted flow. The guide
      catheter balloon was inflated for proximal carotid occlusion. The partially
      deployed stent was slowly pulled back (mechanical thrombectomy step) under
      continuous aspiration. Complete recanalization (TIMI grade 3 flow) was achieved
      in fewer than 66 minutes after femoral access in all patients, with complete clot
      removal in a mean of two thrombectomy attempts. No stent was permanently
      implanted. Two patients developed asymptomatic hemorrhagic transformation
      (11.8%). Two patients presented post-recanalization parenchymal hemorrhage
      (11.8%); one suffered an intracerebral and intraventricular hemorrhage 12 hours
      after a successful and uneventful procedure and died 10 days later. The modified
      Rankin Scale scores were 0 to 2 in 15 patients (88.2%) and 3 in one patient
      (5.9%) at 1 month. In our preliminary experience, rapid stent-based mechanical
      thrombectomy has had unprecedented success.

PMID- 22136734
TI  - Analysis of the treatment of 576 patients with congenital craniovertebral
      junction malformations.
AB  - We aim to report our experience treating craniovertebral junction malformations
      (CVJM) and to investigate the management of this uncommon condition. Between 2000
      and 2009, 629 patients with CVJM underwent surgery in our department. Fifty-three
      patients were lost to follow-up; therefore 576 patients completed follow-up, for
      an average period of 3 years and 2 months. All patients were diagnosed on the
      basis of clinical presentation and imaging features, and we found that anomalies
      of the occipitocervical junction manifested as four major types. Different
      microsurgical treatments were carried out in these patients according to disease
      type, and the effectiveness of individualised treatments was analysed.
      Categorizing patients with CVJM into these four types to simplify this somewhat
      unclear area could provide insight into the pathogenesis of the anomaly and a
      basis for rational surgical treatment.

PMID- 22136735
TI  - Nocturnal headache associated with melatonin deficiency due to a pineal gland
      cyst.
AB  - The cyclic nature of some of headache disorders is closely related to melatonin,
      which is secreted by the pineal gland. We report a 29-year-old male patient with
      a 2.5-year history of headaches that woke him in the middle of the night. These
      headaches were pulsatile and continued until sunrise. During these attacks he
      also suffered from allodynia over the scalp, bilateral conjunctival hyperemia,
      and nervousness. His brain MRI showed a 5mm by 4mm neuroepithelial cyst in the
      pineal gland. The peak plasma melatonin level that was measured at 2 am was 28
      pg/mL. The patient underwent oral melatonin treatment (6 mg/day). After 1 month
      he experienced a 70% reduction in his symptoms. When the melatonin dosage was
      increased to 10mg/day he became headache-free, and 5 months after the treatment
      began, had no complaints. His 5-month follow-up plasma melatonin level at 2 am
      was 61 pg/mL. To our knowledge this is the first report of a patient with
      nocturnal headache associated with a low level of melatonin due to a
      neuroepithelial cyst in the pineal gland.

PMID- 22136736
TI  - Intra-operative neurophysiology during microvascular decompression for hemifacial
      spasm.
AB  - There is evidence that primary hemifacial spasm (HFS) in the majority of patients
      is related to a vascular compression of the facial nerve at its root exit zone
      (REZ). As a consequence, the hyperexcitability of facial nerve generates spasms
      of the facial muscles. Microvascular decompression (MVD) of the facial nerve near
      its REZ has been established as an effective treatment of HFS. Intra-operative
      disappearance of abnormal muscle responses (lateral spread) elicited by
      stimulating one of the facial nerve branches has been used as a method to predict
      MVD effectiveness. Other neurophysiologic techniques, such as facial F-wave,
      blink reflex and facial corticobulbar motor evoked potentials (FCoMEP), are
      feasible to intra-operatively study changes in excitability of the facial nerve
      and its nucleus during MVDs. Intra-operative neuromonitoring with the mentioned
      techniques allows a better understanding of HFS pathophysiology and helps to
      optimise the MVD.

PMID- 22136737
TI  - Contribution of anti-ryanodine receptor antibody to impairment of excitation
      contraction coupling in myasthenia gravis.
AB  - OBJECTIVE: The aim of this study was to elucidate the relationship between the
      impairment of excitation-contraction (E-C) coupling and anti-ryanodine receptor
      (RyR) antibody in patients with myasthenia gravis (MG). METHODS: Masseteric
      compound muscle action potential (CMAP) and mandibular movement-related
      potentials (MRPs) were recorded simultaneously after stimulating the trigeminal
      motor nerve with a needle electrode. The E-C coupling time (ECCT) was calculated
      as the latency difference between CMAP and MRP. For each patient, we selected a
      representative data set when there was no abnormal decrement in response to
      repetitive nerve stimulation. The 26 data sets were divided into an anti-RyR
      positive group (n=12) and an anti-RyR-negative group (n=14). RESULTS: Masseteric
      ECCT was significantly longer (p=0.017) in anti-RyR-positive group (median, mean,
      range; 3.6, 3.8, 3.0-5.9 ms) than in anti-RyR-negative group (3.1, 3.1, 2.7-4.0)
      although there were no significant differences in masseteric CMAP amplitude and %
      decrement between the two groups. The bite force was significantly lower in anti
      RyR-positive group than in normal controls. CONCLUSIONS: Presence of anti-RyR
      antibodies is associated with significantly prolonged masseteric ECCT compared to
      absence of the antibodies in MG. SIGNIFICANCE: Anti-RyR antibody contributes to E
      C coupling impairment in the masseter muscle in patients with MG.

PMID- 22136738
TI  - Impact of depressive and anxiety disorder comorbidity on the clinical expression
      of obsessive-compulsive disorder.
AB  - BACKGROUND: The identification of distinct subtypes based on comorbidity offers
      potential utility in understanding variations in the clinical expression of
      obsessive-compulsive disorder (OCD). Hence, we examined the hypothesis whether
      patients with OCD with major depressive disorder (MDD) or anxiety disorder
      comorbidity would differ from those without in terms of phenomenology. METHODS: A
      total of 545 consecutive patients who consulted a specialty OCD clinic during the
      period 2004 to 2009 at a psychiatric hospital in India formed the sample. They
      were evaluated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS), the Mini
      International Neuropsychiatric Interview, and the Clinical Global Impression
      scale. RESULTS: Among 545 patients, 165 (30%) had current MDD, and 114 (21%) had
      current anxiety disorder comorbidity. Patients with OCD with MDD were mostly
      women who had a greater severity of OCD symptoms, more of obsessions (especially
      religious), greater occurrence of miscellaneous compulsions (need to confess or
      need to touch), higher suicidal risk, and past suicidal attempts. Patients with
      OCD with anxiety disorder had an earlier onset of illness that was associated
      with prior life events, less of compulsions, more of aggressive and hoarding
      obsessions, pathologic doubts, checking, and cognitive compulsions. CONCLUSIONS:
      Obsessive-compulsive disorder, when comorbid with MDD, is more severe and is
      associated with higher suicidal risk. On the other hand, anxiety disorder
      comorbidity seems to influence not so much the morbidity but the phenotypic
      expression of OCD.

PMID- 22136739
TI  - Global isoniazid resistance patterns in rifampin-resistant and rifampin
      susceptible tuberculosis.
AB  - Following the World Health Organization's endorsement of the Xpert(r) MTB/RIF
      assay, which rapidly and simultaneously diagnoses tuberculosis (TB) and detects
      resistance to rifampin (RMP), the question arises to what extent RMP resistance
      is an adequate marker for multidrug-resistant TB (MDR-TB). A retrospective
      analysis of data from >81 countries and subnational settings demonstrated that
      >40% of RMP-resistant isolates from new TB cases did not display resistance to
      isoniazid (INH) in settings with relatively low MDR-TB prevalence (one third of
      all countries and subnational settings). Results indicated the need for INH
      susceptibility testing in addition to RMP susceptibility testing.

PMID- 22136740
TI  - Increasing the folic acid content of maternal or post-weaning diets induces
      differential changes in phosphoenolpyruvate carboxykinase mRNA expression and
      promoter methylation in rats.
AB  - Environmental exposures throughout the life course, including nutrition, may
      induce phenotypic and epigenetic changes. There is limited information about how
      timing affects the nature of such effects induced by a specific nutritional
      exposure. We investigated the effect of increased exposure to folic acid before
      birth or during the juvenile-pubertal period in rats on the epigenetic regulation
      of glucose homeostasis. Rats were fed either a folic acid-adequate (AF; 1 mg/kg
      feed) or a folic acid-supplemented (FS; 5 mg/kg feed) diet from conception until
      delivery and then an AF diet during lactation. Juvenile rats were fed either the
      AF or the FS diet from weaning for 28 d and then an AF diet. Liver and blood were
      collected after a 12 h fast between postnatal days 84 and 90. Maternal FS diet
      increased plasma glucose concentration significantly (P < 0.05) in females, but
      not in males. Post-weaning FS diet decreased glucose concentration significantly
      in females, but increased glucose concentration in males. There were no effects
      of the FS diet on phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in
      males, while the pattern of expression was related to plasma glucose
      concentration in females. The FS diet induced specific changes in the methylation
      of individual CpG in females, but not in males, which were related to the time of
      exposure. Methylation of CpG - 248 increased the binding of CCAAT-enhancer
      binding protein beta to the PEPCK promoter. Together, these findings show that
      both the period during the life course and sex influence the effect of increased
      exposure to folic acid on the epigenetic regulation of PEPCK and glucose
      homeostasis.

PMID- 22136741
TI  - The nasopharynx in infants with cleft lip and palate.
AB  - OBJECTIVE: The purpose of this study was to use three-dimensional computed
      tomography data and computer imaging technology to assess the skeletal components
      of the naso-pharyngeal area in patients with cleft lip and palate and to quantify
      anatomical variations. METHODS: CT scans were obtained from 29 patients of Malay
      origin with cleft lip and palate aged between 0 and 12 months and 12 noncleft
      patients in the same age group, using a GE Lightspeed Plus Scanner housed in
      Hospital Universiti Sains Malaysia. Measurements were obtained using the
      'Persona' three-dimensional software package, developed at Australian
      Craniofacial Unit, Adelaide. RESULTS: The results of the present study show that
      there is an increased nasopharyngeal space in cleft lip and palate that may lead
      to compression of the nasopharyngeal structures, including the Eustachian tube.
      Alterations of the medial pterygoid plate and the hamulus may lead to an
      alteration in the origin and orientation of the tensor veli palatini muscle
      leading to alteration in its function. CONCLUSIONS: These anatomical variations
      may compromise the dilatory mechanism of the Eustachian tube, thus leading to
      recurrent middle ear infections in cleft children and subsequent loss of hearing.

PMID- 22136742
TI  - A model of canine tracheal stenosis induced by radiofrequency cauterization.
AB  - OBJECTIVE: The current methods of management of tracheal stenosis have
      disadvantages and are controversial, therefore ideal experimental animal models
      for the further studies are required. The aim of this study was to establish a
      new model of canine tracheal stenosis by radiofrequency cauterization. METHODS:
      The tracheal cartilage ring was injured by radiofrequency at the level of the
      sixth tracheal ring in 12 mongrel dogs. A fibrolaryngoscope was used to guide the
      procedure. The animals were observed after operation and examined after
      euthanasia. Endoscopic and histological examinations were undertaken to evaluate
      the progress of stenosis. The degree of stenosis was calculated using the
      formula: degree of stenosis=(initial lumen area-final lumen area)/initial lumen
      area * 100%. RESULTS: Tracheal stenosis had developed in all dogs by the 21st day
      post operation. Costal retraction was observed in all dogs after the 18th day
      post operation. At the end of the study, gross and endoscopic examinations showed
      that stenosis had been induced to a satisfactory degree and without any
      complications. The median of the degree of stenosis was 92%, with a range of 84
      94%. Histological examination showed that cartilage was damaged and that
      granulation tissue and collagen fibres had formed. CONCLUSIONS: The model of
      canine tracheal stenosis induced by radiofrequency cauterization is a relatively
      simple, reliable, and reproducible animal model. This model may be useful in the
      development of new methods of treatment for tracheal stenosis.

PMID- 22136743
TI  - From hybridization theory to microarray data analysis: performance evaluation.
AB  - BACKGROUND: Several preprocessing methods are available for the analysis of
      Affymetrix Genechips arrays. The most popular algorithms analyze the measured
      fluorescence intensities with statistical methods. Here we focus on a novel
      algorithm, AffyILM, available from Bioconductor, which relies on inputs from
      hybridization thermodynamics and uses an extended Langmuir isotherm model to
      compute transcript concentrations. These concentrations are then employed in the
      statistical analysis. We compared the performance of AffyILM and other
      traditional methods both in the old and in the newest generation of GeneChips.
      RESULTS: Tissue mixture and Latin Square datasets (provided by Affymetrix) were
      used to assess the performances of the differential expression analysis depending
      on the preprocessing strategy. A correlation analysis conducted on the tissue
      mixture data reveals that the median-polish algorithm allows to best summarize
      AffyILM concentrations computed at the probe-level. Those correlation results are
      equivalent to the best correlations observed using popular preprocessing methods
      relying on intensity values. The performances of each tested preprocessing
      algorithm were quantified using the Latin Square HG-U133A dataset, thanks to the
      comparison of differential analysis results with the list of spiked genes. The
      figures of merit generated illustrates that the performances associated to
      AffyILM(medianpolish), inferred from the present statistical analysis, are
      comparable to the best performing strategies previously reported. CONCLUSIONS:
      Converting probe intensities to estimates of target concentrations prior to the
      statistical analysis, AffyILM(medianpolish) is one of the best performing
      strategy currently available. Using hybridization theory, probe-level estimates
      of target concentrations should be identically distributed. In the future, a
      probe-level multivariate analysis of the concentrations should be compared to the
      univariate analysis of probe-set summarized expression data.

PMID- 22136744
TI  - Chromate-resistance genes in plasmids from antibiotic-resistant nosocomial
      enterobacterial isolates.
AB  - The presence of chromate-resistance genes in enterobacteria was evaluated in a
      collection of 109 antibiotic-resistant nosocomial isolates from nine major cities
      in Mexico. Results were compared with the presence of mercury-resistance genes.
      Susceptibility tests showed that 21% of the isolates were resistant to chromate
      (Cr(R)), whereas 36% were resistant to mercury (Hg(R)). Cr(R) levels were high in
      Klebsiella pneumoniae (61%), low in Enterobacter cloacae (12%) and Escherichia
      coli (4%), and null in Salmonella sp. isolates. Colony hybridization demonstrated
      that the majority of metal-resistant isolates hybridized with chrA gene (87% of
      Cr(R) isolates), encoding a CHR transporter homologue, and merA gene (74% of
      Hg(R) isolates), encoding MerA mercuric reductase, suggesting that most isolates
      expressed these widespread metal-resistance systems. Southern blot hybridization
      of Cr(R) isolates showed that plasmids of 80, 85, and 95 kb from K. pneumoniae
      isolates, and of 100 kb from an E. cloacae isolate, contained chrA-related
      sequences. These plasmids belonged to IncN or IncP incompatibility groups, and
      conferred Cr(R), as well as multiple antibiotic resistance, when transferred by
      conjugation to an E. coli standard strain. These data indicated that Cr(R) genes
      may be distributed among clinical enterobacteria via conjugative plasmids,
      probably by coselection with antibiotic-resistant genes.

PMID- 22136745
TI  - Population mobility and the changing epidemics of HIV-2 in Portugal.
AB  - INTRODUCTION: Portugal is the European country with the highest frequency of HIV
      2 infection, which is mainly concentrated in West Africa. The cumulative number
      of notified HIV-2 infections in Portugal was 1813 by the end of December 2008. To
      better characterize the dynamics of HIV-2 infection in the country and to obtain
      data that may be of use in the prevention of the spread of HIV-2, we evaluated a
      large pooled sample of patients. PATIENTS AND METHODS: Five Portuguese hospitals
      provided data on HIV-2-infected patients from 1984 to the end of 2007. Data
      concerning demographic characteristics and clinical variables were extracted.
      Patients were stratified according to date of diagnosis in approximately 5-year
      categories. RESULTS: The sample included 442 patients, accounting for 37% of all
      HIV-2 infections notified in Portugal during that period. HIV-2-infected patients
      showed clearly different characteristics according to the period of diagnosis.
      Until 2000, the majority of HIV-2-infected patients were Portuguese-born males
      living in the north of the country. From 2000 to 2007, most of the patients
      diagnosed with HIV-2 infection had a West African origin, were predominantly
      female and were living in the capital, Lisbon. The average age at diagnosis and
      loss to follow-up significantly increased over time. CONCLUSION: HIV-2 infection
      has been documented in Portugal since the early 1980s and its epidemiology
      appears to reflect changes in population movement. These include the movements of
      soldiers and repatriates from African territories during the independence wars
      and, later, migration and mobility from high-endemicity areas. The findings of
      this study stress the importance of promoting migrant-sensitive health care.

PMID- 22136746
TI  - Effect of estrogen therapy on adipocytokines in ovariectomized-aged rats.
AB  - AIM: Obesity is a chronic disease that is characterized by excessive accumulation
      of body fat. The physiological changes associated with estrogen deprivation in
      menopause have a significant impact on total body fat and adipose tissue
      distribution. Adipocytokines, such as adiponectin and leptin are related to
      adipose tissue, and their levels are affected by estrogen. The aim of the present
      study was to investigate the alteration of adipocytokine levels with estrogen
      therapy. MATERIAL AND METHODS: Aged Wistar albino rats were divided into two main
      groups: control (C) and ovariectomized (OVX). Six months after ovariectomy, the
      ovariectomized group was divided into four subgroups: two ovariectomized groups
      received saline (OVX) and sesame oil (OVX+S.oil), and two groups received
      physiological dose (OVX+PhyE2) and pharmacological dose (OVX+PharmE2) estrogen (2
      and 20ug/kg per day, respectively). Body weight was monitored weekly for 6weeks.
      Adiponectin, leptin and homocysteine levels were measured from blood samples
      before and after treatment. RESULTS: Body weight increased in OVX, OVX+S.oil and
      OVX+PhyE2 over 6weeks (P<0.001). Adiponectin levels were significantly decreased
      in the OVX+S.oil and OVX+PhyE2 groups (P=0.017 and P=0.008, respectively). Leptin
      level was significantly decreased in the OVX+PharmE2 group (P=0.042).
      Homocysteine level was decreased in the OVX+S.oil group (P=0.037). CONCLUSION:  
      Adipocytokines may play a role in the pathogenesis of cancer or obesity-related
      complications in menopause. Estrogen therapy may reduce these complications by
      changing the levels of adipocytokines.

PMID- 22136747
TI  - [Epidemiology of Clostridium difficile infection in Spain].
AB  - There has been increasing interest in Clostridium difficile infection (CDI) due
      its association with healthcare and its impact on morbidity and mortality in the
      elderly. During the last few years there has been a growing increase in the
      number of published studies on the incidence, changes on the clinical
      presentation and on the epidemiology, with the description of new risk factors.
      The frequency of CDI in Spain is not sufficiently characterised. The available
      data indicates that incidence is within the range of that of surrounding
      countries but increasing. Furthermore, the high and growing use of broad spectrum
      antibiotics, both in our hospitals and in the community setting, are factors that
      favour the increase of the disease. The hyper-virulent ribotype 027 has not
      spread in our hospitals. We need to know with enhanced validity and accuracy the
      incidence of CDI, both community and healthcare-associated, the information on
      outbreaks, the incidence on certain population groups, the characterisation of
      circulating ribotypes and the impact of the disease in terms of mortality and
      health costs. We need to implement programs for the improvement of antibiotic
      therapy in the hospital, as well as in the community. Furthermore, the knowledge
      and the performance of standard precautions need to be improved, particularly
      hand hygiene, and the specific measures to limit the transmission of C. difficile
      among the healthcare institutions.

PMID- 22136748
TI  - Association of depression and urolithiasis.
AB  - OBJECTIVES: To study the hypothesis that patients with urolithiasis would have a
      higher prevalence of depression compared to the general population. Urolithiasis
      is associated with frequent recurrences. Patients with urolithiasis may develop a
      chronic condition associated with poor quality of life and depression. The
      frequency and severity of stones episodes would relate to depression. METHODS: In
      an institutional review board-approved study; we prospectively recruited 115
      patients who were evaluated for urolithiasis. Patients completed an Emory stone
      questionnaire covering demographics and a validated CES-D depression
      questionnaire. Depression scores were compared with U.S. norms. Demographics and
      clinical variables were analyzed. RESULTS: On the CES-D depression questionnaire
      30.4% of patients scored >= 16, a "significant level of physiological distress."
      The U.S. lifetime prevalence of depression was 16.5%. Determinants of depression
      included the following: family history of urolithiasis (OR = 3.49, CI = 1.51;
      8.07), stone episode within the last 12 months (OR = 2.77, CI = 1.18; 6.53), and
      >1 emergency room visits for stone disease (OR = 2.61, CI = 1.14; 5.99). Patients
      with Charlson comorbidity indexes of <= 1 were more likely to be depressed than
      those scoring >1 (OR 2.89, CI = 1.20; 6.95). There were no significant
      associations with age at first stone, number of lifetime stones, number of
      surgeries, number of workdays missed, and need for dietary modifications or
      medications for stone prevention. CONCLUSIONS: The prevalence of depression in
      our patient cohort with urolithiasis was substantially greater than societal
      norms. Multiple stone-related factors were associated with significant
      psychological distress. Appreciation of this issue may allow better patient care.

PMID- 22136749
TI  - Neural mechanisms mediating the effects of expectation in visceral placebo
      analgesia: an fMRI study in healthy placebo responders and nonresponders.
AB  - This functional magnetic resonance imaging study analysed the behavioural and
      neural responses during expectation-mediated placebo analgesia in a rectal pain
      model in healthy subjects. In N=36 healthy subjects, the blood oxygen level
      dependent (BOLD) response during cued anticipation and painful rectal stimulation
      was measured. Using a within-subject design, placebo analgesia was induced by
      changing expectations regarding the probability of receiving an analgesic drug to
      0%, 50%, and 100%. Placebo responders were identified by median split based on
      pain reduction (0% to 100% conditions), and changes in neural activation
      correlating with pain reduction in the 0% and 100% conditions were assessed in a
      regions-of-interest analysis. Expectation of pain relief resulted in overall
      reductions in pain and urge to defecate, and this response was significantly more
      pronounced in responders. Within responders, pain reduction correlated with
      reduced activation of dorsolateral and ventrolateral prefrontal cortices,
      somatosensory cortex, and thalamus during cued anticipation (paired t tests on
      the contrast 0%>100%); during painful stimulation, pain reduction correlated with
      reduced activation of the thalamus. Compared with nonresponders, responders
      demonstrated greater placebo-induced decreases in activation of dorsolateral
      prefrontal cortex during anticipation and in somatosensory cortex, posterior
      cingulate cortex, and thalamus during pain. In conclusion, the expectation of
      pain relief can substantially change perceived painfulness of visceral stimuli,
      which is associated with activity changes in the thalamus, prefrontal, and
      somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate
      psychological components of the pain response relevant to the pathophysiology and
      treatment of chronic abdominal pain.

PMID- 22136750
TI  - Cognitive dimensions of anger in chronic pain.

PMID- 22136751
TI  - Association of vitamin K status with adiponectin and body composition in healthy
      subjects: uncarboxylated osteocalcin is not associated with fat mass and body
      weight.
AB  - Osteocalcin (OC) is a vitamin K-dependent protein found in bone and in
      circulation. High serum gamma-carboxylated OC reflects a high, and high
      uncarboxylated OC (ucOC) reflects a low vitamin K status. A revolutionary
      hypothesis is that ucOC acts as a hormone improving glucose handling and reducing
      fat mass. The objective was to test the logical extrapolation of the ucOC hormone
      hypothesis to humans that elevated ucOC is associated with higher body weight,
      BMI and fat mass. In a cross-sectional analysis, the associations of vitamin K
      status with circulating adiponectin and body composition were investigated in 244
      postmenopausal women (study I). The effects of vitamin K treatment on
      adiponectin, body weight and BMI were investigated in archived samples from forty
      two young men and women who received varying doses of menaquinone-7 during 12
      weeks (study II) and from a cohort of 164 postmenopausal women who participated
      in a 3-year placebo-controlled trial on 45 mg menaquinone-4 (MK-4) (study III).
      No association was found between vitamin K status and circulating adiponectin
      before or after vitamin K supplementation. A higher carboxylation of OC was
      significantly correlated with lower body weight, BMI and fat mass of the trunk.
      Women taking MK-4 maintained their baseline body weight and BMI, whereas women
      taking placebo showed significant increases in both indices. These findings
      demonstrate that a high vitamin K status of bone has no effect on circulating
      adiponectin in healthy people and long-term vitamin K supplementation does not
      increase weight in healthy postmenopausal women.

PMID- 22136752
TI  - Experimental study of a novel mechanical connector for sutureless open arterial
      anastomosis.
AB  - OBJECTIVES: This study assessed the feasibility and efficacy of a new sutureless
      connector for end-to-end arterial anastomosis. METHODS: The anastomotic device is
      a connector consisting of a bare-metal stent with spikes covering its outer
      surface, which is introduced through the prosthesis. The seal of the anastomosis
      is obtained by inflating a balloon anchoring the stent with the spikes in the
      prosthesis and in the receiving artery. This experiment was conducted in three
      phases: (1) A feasibility study was done on four cadaveric femoral arteries using
      a polytetrafluoroethylene prosthesis, with measurement of the penetration of the
      spikes into the layers of the arterial wall. (2) Bench tests were conducted in
      seven automated and in seven sutured anastomoses. Anastomosis sealing was tested
      using a pump system (<=250 mm Hg) in a water-filled closed circuit. (3) The
      infrarenal aorta of seven pigs was replaced with a 6- to 8-mm diameter
      prosthesis, using this automated device for the proximal anastomosis. The distal
      anastomosis was handsewn on the aortic bifurcation. After completion angiography,
      animals were euthanized for macroscopic and histologic studies of the aorta,
      connector, and prosthesis. Explantations were done immediately (2 pigs), and at
      15 (2 pigs), at 30 (2 pigs), and 42 days (1 pig). Study end points were the
      automated anastomosis time compared with manual suturing, leakage, mechanical
      strength, and patency of the anastomosis together with the histologic changes of
      the aortic wall in contact with the spiked stent. RESULTS: Tests performed on
      four cadaveric arteries showed complete penetration of the spikes into the
      arterial wall layers without metal fracture. Tests of traction showed that the
      median force needed to rupture the automated anastomosis was 18.3 N
      (interquartile range [IQR], 17.7-19.9 N), with no significant difference from the
      handmade anastomosis (19.5 N; IQR, 17.9-20.2 N, P = .33). No leakage was
      demonstrated in vitro with a pulsatile flow and a pressure up to 250 mm Hg. The
      median automated anastomosis time on pig aorta was 2.4 minutes (IQR, 1.4-3.3 min)
      vs 17.0 minutes (IQR, 15.1-17.2 minutes) for the handmade aortic anastomosis
      performed on the same animals (P = .002). There was no anastomotic leak.
      Histology showed incorporation of the connector spikes in the aortic wall,
      without intimal hyperplasia or false aneurysm. CONCLUSIONS: This preliminary
      study confirms the feasibility of this sutureless system, suggesting its
      usefulness for a faster and simpler anastomosis in hybrid arterial surgery.

PMID- 22136753
TI  - Streptomyces coelicolor RedP and FabH enzymes, initiating undecylprodiginine and
      fatty acid biosynthesis, exhibit distinct acyl-CoA and malonyl-acyl carrier
      protein substrate specificities.
AB  - RedP is proposed to initiate undecylprodiginine biosynthesis in Streptomyces
      coelicolor by condensing an acyl-CoA with malonyl-ACP and is homologous to FabH
      that catalyzes the same reaction for initiation of fatty acid biosynthesis.
      Herein, we report the substrate specificities of RedP and FabH from assays using
      pairings of two acyl-CoA substrates (acetyl-CoA and isobutyryl-CoA) and two
      malonyl-ACP substrates (malonyl-RedQ and malonyl-FabC). RedP activity was
      observed only with a pairing of acetyl-CoA and malonyl-RedQ, consistent with its
      proposed role in initiating the formation of acetyl-CoA-derived prodiginines.
      Malonyl-FabC is not a substrate for RedP, indicating that ACP specificity is one
      of the factors that permit a separation between prodiginine and fatty acid
      biosynthetic processes. FabH demonstrated greater catalytic efficiency for
      isobutyryl-CoA in comparison with acetyl-CoA using malonyl-FabC, consistent with
      the observation that in streptomycetes, a broad mixture of fatty acids is
      synthesized, with those derived from branched-chain acyl-CoA starter units
      predominating. Diminished FabH activity was also observed using malonyl-RedQ with
      the same preference for isobutyryl-CoA, completing biochemical and genetic
      evidence that in the absence of RedP this enzyme can produce branched-chain alkyl
      prodiginines.

PMID- 22136754
TI  - Pregnancy outcomes in adolescents in the UK and Ireland growing up with HIV.
AB  - OBJECTIVES: Adolescents with HIV infection acquired perinatally or in early
      childhood are becoming sexually active, but little is known about fertility and
      pregnancy outcomes. Multicentre data on pregnancy outcomes in this population are
      described here. METHODS: A retrospective case note review of pregnant women with
      perinatal/early acquired HIV infection, conceiving before 1 September 2009 and
      attending participating centres in the UK and Ireland, was carried out. RESULTS:
      Among 252 women with perinatal/early acquired infection aged 12 years and older
      under follow-up in 21 centres, 42 pregnancies were reported in 30 women (19 women
      with a single pregnancy, 10 women with two pregnancies, and one woman with three
      pregnancies). Fifteen women (50%) had previous AIDS-defining diagnoses. The
      median age at first reported pregnancy was 18 years (range 14-22 years). Of the
      42 pregnancies, 34 (81%) were reportedly unplanned, 31 (74%) involved regular
      partners, and in 21 (50%) of the 42 pregnancies the partners were reported to be
      unaware of maternal HIV status. Fifteen of the 42 pregnancies (36%) were
      electively terminated, six of the 42 (14%) resulted in first-trimester
      miscarriages and 21 of the 42 (50%) resulted in live births. Maternal viral load
      was detectable close to delivery in seven of 21 pregnancies (33%). Four infants
      required neonatal intensive care, three of whom were delivered preterm. One
      infant is HIV infected, there are ongoing concerns about the development of three
      of 21 infants (14%), and two of 21 (10%) have been fostered. CONCLUSIONS: Despite
      access to ongoing sexual health and contraceptive services, unplanned pregnancies
      are occurring in young women growing up with HIV. Pregnancy care and prevention
      of onward transmission require complex case management for this emerging
      population.

PMID- 22136755
TI  - Recalcitrance of bacterial vaginosis among herpes-simplex-virus-type-2
      seropositive women.
AB  - AIM: The multifactorial etiology of bacterial vaginosis (BV) impedes development
      of effective treatment and prevention strategies. Herein, we evaluated the
      effects of herpes simplex virus type 2 (HSV-2), a suspected BV risk factor, on
      vaginal flora composition. MATERIALS AND METHODS:   Correlations between HSV-2
      infection and BV were prospectively explored among 12 HSV-2-seropositive women
      with asymptomatic BV who were asked to collect daily vaginal swab specimens for
      Gram stain analysis of vaginal flora and determination of HSV-2 shedding
      frequencies during the 1month before and after metronidazole therapy. RESULTS:
      Unlike prior longitudinal studies that reported rapid fluctuations in vaginal
      flora composition and frequent episodes of spontaneously resolving BV, we found
      that 99.4% (310/312) of vaginal smears collected before initiation of
      metronidazole were consistent with a diagnosis of BV. Effectiveness of
      metronidazole therapy was also much lower than previously reported in studies not
      restricting enrollment to HSV-2-seropositive women; we observed a BV recurrence
      rate of 89% in the first month after completion of therapy while the median time
      to this recurrence occurred only 14days after treatment. CONCLUSIONS: Our study
      demonstrates BV recalcitrance among HSV-2-infected women and provides additional
      evidence for a linkage between this chronic viral infection and abnormal vaginal
      flora. Additional work will be needed to define mechanisms responsible for this
      correlation and to determine if vaginal flora health of HSV-2-infected women is
      improved by medications that suppress HSV-2 shedding.

PMID- 22136756
TI  - Predicting urinary creatinine excretion and its usefulness to identify incomplete
      24 h urine collections.
AB  - Studies using 24 h urine collections need to incorporate ways to validate the
      completeness of the urine samples. Models to predict urinary creatinine excretion
      (UCE) have been developed for this purpose; however, information on their
      usefulness to identify incomplete urine collections is limited. We aimed to
      develop a model for predicting UCE and to assess the performance of a creatinine
      index using para-aminobenzoic acid (PABA) as a reference. Data were taken from
      the European Food Consumption Validation study comprising two non-consecutive 24
      h urine collections from 600 subjects in five European countries. Data from one
      collection were used to build a multiple linear regression model to predict UCE,
      and data from the other collection were used for performance testing of a
      creatinine index-based strategy to identify incomplete collections. Multiple
      linear regression (n 458) of UCE showed a significant positive association for
      body weight (beta = 0.07), the interaction term sex * weight (beta = 0.09,
      reference women) and protein intake (beta = 0.02). A significant negative
      association was found for age (beta = -0.09) and sex (beta = -3.14, reference
      women). An index of observed-to-predicted creatinine resulted in a sensitivity to
      identify incomplete collections of 0.06 (95 % CI 0.01, 0.20) and 0.11 (95 % CI
      0.03, 0.22) in men and women, respectively. Specificity was 0.97 (95 % CI 0.97,
      0.98) in men and 0.98 (95 % CI 0.98, 0.99) in women. The present study shows that
      UCE can be predicted from weight, age and sex. However, the results revealed that
      a creatinine index based on these predictions is not sufficiently sensitive to
      exclude incomplete 24 h urine collections.

PMID- 22136757
TI  - The expression of the cerato-platanin gene is related to hyphal growth and
      chlamydospores formation in Ceratocystis platani.
AB  - Cerato-platanin (CP) is a protein produced by Ceratocystis platani, the causal
      agent of canker stain disease of plane trees. CP is the first member of the
      'cerato-platanin family', and its role as a pathogen-associated molecular pattern
      (PAMP), inducing defence responses both in host and nonhost plants, is
      established. However, the primary role of CP and its homologues in the fungal
      life remains unknown. In the present work, we investigated the regulation of the
      cp gene during the in vitro growth of C. platani in different conditions and
      under the effect of potential stress factors. Fungal growth and conidiogenesis
      were also analysed. Results showed that cp is a single-copy gene whose expression
      level is strictly associated with hyphal growth and with chlamydospores
      formation. The analysis of a 1368 bp 5'-flanking region revealed putative motifs
      that could be involved in the regulation of gene expression in response to stress
      and developmental cues. Taking into account the localization of CP in the fungal
      cell wall and the recently published 3D structure of the protein, our results
      support a role for CP in growth and developmental processes of C. platani.

PMID- 22136758
TI  - Development and characterization of 5 canine B-cell lymphoma cell lines.
AB  - Canine and human lymphoma share similar characteristics in disease development
      and response to therapy. Translational research can be furthered using tools such
      as canine cell lines to model therapeutic compounds and strategies. We developed
      5 B-cell lymphoma cell lines from dogs with confirmed large B-cell lymphoma.
      These cell lines were CD3, CD18, CD20, and CD90 positive with variable CD79a,
      CD1c and CD34 expression. All cell lines were tumorigenic in Nu/nu mice and were
      wild type for p53. Canine lymphoma cell lines serve as an important resource for
      translational lymphoma research.

PMID- 22136759
TI  - Impaired lung function in individuals chronically exposed to biomass combustion.
AB  - BACKGROUND: The use of biomass for cooking and heating is considered an important
      factor associated with respiratory diseases. However, few studies evaluate the
      amount of particulate matter less than 2.5 MUm in diameter (PM2.5), symptoms and
      lung function in the same population. OBJECTIVES: To evaluate the respiratory
      effects of biomass combustion and compare the results with those of individuals
      from the same community in Brazil using liquefied petroleum gas (Gas). METHODS:
      1402 individuals in 260 residences were divided into three groups according to
      exposure (Gas, Indoor-Biomass, Outside-Biomass). Respiratory symptoms were
      assessed using questionnaires. Reflectance of paper filters was used to assess
      particulate matter exposure. In 48 residences the amount of PM2.5 was also
      quantified. Pulmonary function tests were performed in 120 individuals. RESULTS:
      Reflectance index correlated directly with PM2.5 (r=0.92) and was used to
      estimate exposure (ePM2.5). There was a significant increase in ePM2.5 in Indoor
      Biomass and Outside-Biomass, compared to Gas. There was a significantly increased
      odds ratio (OR) for cough, wheezing and dyspnea in adults exposed to Indoor
      Biomass (OR=2.93, 2.33, 2.59, respectively) and Outside-Biomass (OR=1.78, 1.78,
      1.80, respectively) compared to Gas. Pulmonary function tests revealed both Non
      Smoker-Biomass and Smoker-Gas individuals to have decreased %predicted-forced
      expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC)
      as compared to Non-Smoker-Gas. Pulmonary function tests data was inversely
      correlated with duration and ePM2.5. The prevalence of airway obstruction was 20%
      in both Non-Smoker-Biomass and Smoker-Gas subjects. CONCLUSION: Chronic exposure
      to biomass combustion is associated with increased prevalence of respiratory
      symptoms, reduced lung function and development of chronic obstructive pulmonary
      disease. These effects are associated with the duration and magnitude of exposure
      and are exacerbated by tobacco smoke.

PMID- 22136760
TI  - Dental implantology. Preface.

PMID- 22136761
TI  - Macrobenthic community structure in the northern Saudi waters of the Gulf, 14
      years after the 1991 oil spill.
AB  - The 1991 Gulf oil spill heavily impacted the coastal areas of the Saudi waters of
      the Arabian Gulf and recent studies have indicated that even 15 years after the
      incident, macrobenthos had not completely recovered in the sheltered bays in the
      affected region such as, Manifa Bay. This study investigates the community
      conditions of macrobenthos in the open waters in one of the impacted areas, Al
      Khafji waters, about 14 years after the spill. Diversity measures and community
      structure analyses indicate a healthy status of polychaete communities. The BOPA
      index reveals that oil sensitive amphipods were recolonized in the study area.
      This confirms that the benthic communities of the oil spill impacted area had
      taken only <14 years to recover in the open waters of the impacted areas. The
      study also reveals the existence of three distinct polychaete communities along
      the depth and sediment gradients.

PMID- 22136762
TI  - Nanoporous polystyrene fibers for oil spill cleanup.
AB  - The development of oil sorbents with high sorption capacity, low cost, scalable
      fabrication, and high selectivity is of great significance for water
      environmental protection, especially for oil spillage on seawater. In this work,
      we report nanoporous polystyrene (PS) fibers prepared via a one-step
      electrospinning process used as oil sorbents for oil spill cleanup. The
      oleophilic-hydrophobic PS oil sorbent with highly porous structures shows a motor
      oil sorption capacity of 113.87 g/g, approximately 3-4 times that of natural
      sorbents and nonwoven polypropylene fibrous mats. Additionally, the sorbents also
      exhibit a relatively high sorption capacity for edible oils, such as bean oil
      (111.80 g/g) and sunflower seed oil (96.89 g/g). The oil sorption mechanism of
      the PS sorbent and the sorption kinetics were investigated. Our nanoporous
      material has great potential for use in wastewater treatment, oil accident
      remediation and environmental protection.

PMID- 22136763
TI  - Monitoring of suspended sediment variation using Landsat and MODIS in the
      Saemangeum coastal area of Korea.
AB  - Suspended sediment concentration (SS) is an important indicator of marine
      environmental changes due to natural causes such as tides, tidal currents, and
      river discharges, as well as human activities such as construction in coastal
      regions. In the Saemangeum area on the west coast of Korea, construction of a
      huge tidal dyke for land reclamation has strongly influenced the coastal
      environment. This study used remotely sensed data to analyze the SS changes in
      coastal waters caused by the dyke construction. Landsat and MODIS satellite
      images were used for the spatial analysis of finer patterns and for the detailed
      temporal analysis, respectively. Forty Landsat scenes and 105 monthly composite
      MODIS images observed during 1985-2010 were employed, and four field campaigns
      (from 2005 to 2006) were performed to verify the image-derived SS. The results of
      the satellite data analyses showed that the seawater was clear before the dyke
      construction, with SS values lower than 20 g/m(3). These values increased
      continuously as the dyke construction progressed. The maximum SS values appeared
      just before completion of the fourth dyke. Values decreased to below 5 g/m(3)
      after dyke construction. These changes indicated tidal current modification. Some
      eddies and plumes were observed in the images generated from Landsat data.
      Landsat and MODIS can reveal that coastal water turbidity was greatly reduced
      after completion of the construction.

PMID- 22136764
TI  - Towards ecologically relevant targets for river pollutant loads to the Great
      Barrier Reef.
AB  - Degradation of coastal ecosystems in the Great Barrier Reef (GBR), Australia, has
      been linked with a decline in water quality from land-based runoff. This paper
      examines the reduction in current end-of-catchment loads required for total
      suspended solids (TSS) and dissolved inorganic nitrogen (DIN) to achieve GBR
      water quality guidelines. Based on first-order estimates of sustainable pollutant
      loads, current TSS and DIN loads would need to be reduced by approximately
      7000ktons/y (41%) and 6000tons/y (38%), respectively. Next, these estimated
      reductions for TSS and DIN are compared with Reef Plan targets for anthropogenic
      sediment (-20% by 2020) and nitrogen (-50% by 2013) loads. If successful, these
      targets will accomplish approximately 40% of TSS and 92% of DIN load reductions
      required to achieve sustainable loads to the GBR lagoon. These first-order
      estimates elucidate the need to establish ecologically relevant targets for river
      pollutant loads to the GBR for management and policy.

PMID- 22136765
TI  - Synthesis, radiofluorination and pharmacological evaluation of a fluoromethyl
      spirocyclic PET tracer for central sigma1 receptors and comparison with
      fluoroalkyl homologs.
AB  - The spirocyclic sigma(1) receptor ligand 1 (1'-benzyl-3-(fluoromethyl)-3H
      spiro[[2]benzofuran-1,4'-piperidine]) was prepared in four steps starting from
      methoxy derivative 5. Due to its high sigma(1) affinity (K(i)=0.74nM) and
      selectivity against several other relevant targets, 1 was investigated as (18)F
      labeled PET tracer and its biological properties were compared with those of
      homologous fluoroalkyl derivatives 2-4. The fluoromethyl derivative 1 was faster
      metabolized in vitro than homologs 2-4. In contrast to the radiosynthesis of
      [(18)F]2-4, the nucleophilic substitution of the tosylate 15 using the K[(18)F]F
      K(222)-carbonate complex required heating to 150 degrees C in DMSO to achieve
      high labeling efficiencies. Whereas radiometabolites of [(18)F]2-4 were not
      detected in vivo in the brain of mice, two radiometabolites of [(18)F]1 were
      found. Analysis of ex vivo autoradiography images provided rather low target-to
      nontarget ratio for [(18)F]1 compared with [(18)F]2-4. [(18)F]1 showed a fast
      uptake in the brain, which decreased continuously over time. The brain-to-plasma
      ratio of the radiotracer [(18)F]1 was only exceeded by the fluoroethyl tracer
      [(18)F]2.

PMID- 22136766
TI  - Syntheses of 1,2-annulated and 1-spiroannulated carbohydrate derivatives: recent
      developments.
AB  - A variety of different strategies has been used for the 1,2-annulation and the 1
      spiroannulation of further rings to monosaccharides. This short review presents
      some recent methods to access such structures involving radical chemistry,
      cycloadditions, Michael reactions and metal-catalyzed transformations.

PMID- 22136767
TI  - Increasing dosage of statins in patients with coronary heart disease in China: a
      note of caution.

PMID- 22136768
TI  - 16S partial gene mitochondrial DNA and internal transcribed spacers ribosomal DNA
      as differential markers of Trichuris discolor populations.
AB  - Comparative morphological, biometrical and molecular studies of Trichuris
      discolor isolated from Bos taurus from Spain and Iran was carried out.
      Furthermore, Trichuris ovis isolated from B. taurus and Capra hircus from Spain
      has been, molecularly, analyzed. Morphological studies revealed clear differences
      between T. ovis and T. discolor isolated from B. taurus but differences were not
      observed between populations of T. discolor isolated from different geographical
      regions. Nevertheless, the molecular studies based on the amplification and
      sequencing of the internal transcribed spacers 1 and 2 ribosomal DNA and 16S
      partial gene mitochondrial DNA showed clear differences between both populations
      of T. discolor from Spain and Iran suggesting two cryptic species. Phylogenetic
      studies corroborated these data. Thus, phylogenetic trees based on ITS1, ITS2 and
      16S partial gene sequences showed that individuals of T. discolor from B. taurus
      from Iran clustered together and separated, with high bootstrap values, of T.
      discolor isolated from B. taurus from Spain, while populations of T. ovis from B.
      taurus and C. hircus from Spain clustered together but separated with high
      bootstrap values of both populations of T. discolor. Furthermore, a comparative
      phylogenetic study has been carried out with the ITS1and ITS2 sequences of
      Trichuris species from different hosts. Three clades were observed: the first
      clustered all the species of Trichuris parasitizing herbivores (T. discolor, T.
      ovis, Trichuris leporis and Trichuris skrjabini), the second clustered all the
      species of Trichuris parasitizing omnivores (Trichuris trichiura and Trichuris
      suis) and finally, the third clustered species of Trichuris parasitizing
      carnivores (Trichuris muris, Trichuris arvicolae and Trichuris vulpis).

PMID- 22136769
TI  - Evaluation of indirect TaSP enzyme-linked immunosorbent assay for diagnosis of
      tropical theileriosis in cattle (Bos indicus) and water buffaloes (Bubalus
      bubalis) in Egypt.
AB  - The aim of the present study was to evaluate the validity of Theileria annulata
      surface protein (TaSP)-ELISA, in comparison with traditional microscopic test,
      for the diagnosis of T. annulata infection among Egyptian baladi cattle (Bos
      taurus) and water buffaloes (Bubalus bubalis). Molecular confirmation of
      infection using T. annulata merozoite surface (Tams-1) target amplification by
      PCR was used as a gold standard. A total of 76 clinically suspected animals
      including 64 baladi cattle and 12 water buffaloes were investigated in the
      current study by the three methods. Based on the PCR-confirmed results, the
      evaluation study revealed higher sensitivity of TaSP-ELISA (72.9% and 75%) as
      compared to microscopic examination (58.3% and 50%) among cattle and buffaloes,
      respectively. On the other hand, the specificity of TaSP-ELISA in diagnosis of T.
      annulata infection was higher (87.5%) in baladi cattle as compared to water
      buffaloes (37.5%). In conclusion, TaSP-ELISA was shown to be suitable for the
      diagnosis of T. annulata infection in cattle under field conditions.

PMID- 22136770
TI  - Molecular evidence of shared hookworm Ancylostoma tubaeforme haplotypes between
      the critically endangered Iberian lynx and sympatric domestic cats.
AB  - Hookworms of the genus Ancylostoma are the most pathogenic parasites of young
      cats, and A. tubaeforme may cause morbidity or mortality in young individuals of
      the most endangered felid species in the world, the Iberian lynx (Lynx pardinus).
      Since the transmission of monoxenous parasites is related to host density and
      remaining lynx populations are currently very small, the presence of reservoir
      hosts may be necessary for the maintenance of the hookworm life-cycle, the
      domestic cat being the most likely reservoir of A. tubaeforme. In order to
      confirm this hypothesis, the mitochondrial cytochrome c oxidase subunit I gene
      (Cox I) sequences of three A. tubaeforme specimens from a road-killed Iberian
      lynx from Donana were compared with 14 specimens retrieved from five sympatric
      free-roaming cats from the same area, and with six specimens from three free
      roaming cats from the Mediterranean island of Mallorca. Gene fragments (300 bp)
      from 23 A. tubaeforme individuals representing 16 different haplotypes were
      obtained. A statistical parsimony haplotype network analysis showed that the
      three specimens infecting an Iberian lynx corresponded to two different
      haplotypes, one of which was identical to a specimen in a cat found only 10 km
      from the lynx. Specimens from the Iberian lynx and those from cats in Donana were
      only 1.03% genetically divergent, whereas specimens from Mallorca cats and those
      from Donana cats and the lynx diverged by 1.33% and 1.36%, respectively. The
      existence of shared haplotypes of hookworms between lynx and cat reinforces the
      hypothesis that the abundant sympatric domestic cat population is acting as a
      reservoir for A. tubaeforme infection in the endangered Iberian lynx.

PMID- 22136771
TI  - Ablation of esophageal squamous neoplasia: addressing the bigger picture.

PMID- 22136772
TI  - Improved risk assessment in upper GI bleeding.

PMID- 22136774
TI  - Transoral gastroplasty for morbid obesity: a multicenter trial with a 1-year
      outcome.
AB  - BACKGROUND: Bariatric surgery is associated with specific complications and
      mortality. Transoral gastroplasty (TOGA) is a transoral restrictive bariatric
      procedure that might offer the benefits of surgery with a reduced complication
      rate. OBJECTIVE: To evaluate the safety and efficacy of TOGA at 12-month follow
      up. DESIGN: Prospective, multicenter, single-arm trial. SETTING: Two tertiary
      care referral medical centers. PATIENTS: This study involved 67 patients (average
      age 41.0 years, 47 women, baseline body mass index [BMI] 41.5 kg/m(2); 20
      patients with BMI <40). INTERVENTION: The TOGA procedures were performed by using
      2 stapling devices that were used to create a small, restrictive pouch along the
      lesser gastric curvature. The pouch is designed to give the patient a sustained
      feeling of satiety after small meals. MAIN OUTCOME MEASUREMENTS: Excess weight
      loss, excess BMI loss, safety, and improvements in quality of life, obesity
      related comorbidities, and medication use. RESULTS: Fifty-three patients were
      available at the 12-month follow-up. Excess BMI loss was 33.9%, 42.6%, and 44.8%
      at 3, 6, and 12 months, respectively. At 12 months, excess BMI loss was 52.2% for
      patients with a baseline BMI of <40.0 and 41.3% for patients with a baseline BMI
      of >= 40.0 (P < .05). At 12 months, hemoglobin A(1c) levels decreased from 7.0%
      at baseline to 5.7% (P = .01); triglyceride levels decreased from 142.9 mg/dL to
      98 mg/dL (P < .0001); high-density lipoprotein levels increased from 47.0 mg/dL
      to 57.5 mg/dL (P < .0001). Two complications occurred: a case of respiratory
      insufficiency and an asymptomatic pneumoperitoneum treated conservatively.
      LIMITATIONS: Small number of patients. Short-term follow-up. Twenty-one percent
      of patients were not available for the 12-month follow-up. CONCLUSION: The TOGA
      procedure allowed a substantial weight loss 1 year after the operation without
      severe complications. A long-term evaluation is needed before definitive
      conclusions can be drawn.

PMID- 22136775
TI  - Usefulness of magnifying endoscopy with narrow-band imaging for determining the
      horizontal extent of early gastric cancer when there is an unclear margin by
      chromoendoscopy (with video).
AB  - BACKGROUND: Magnifying endoscopy (ME) with narrow-band imaging (NBI) may allow
      reliable delineation of the horizontal extent of early gastric cancers before
      endoscopic submucosal dissection (ESD). However, the advantages of ME with NBI
      over standard endoscopy with dye spraying (chromoendoscopy [CE]) have yet to be
      elucidated. OBJECTIVE: To investigate the usefulness and limitations of ME with
      NBI when CE is unsuccessful for determining the horizontal extent of early
      gastric cancer. DESIGN: Case series. SETTING: Single tertiary referral center.
      MATERIALS: Series of 350 consecutive early gastric cancers resected en bloc using
      ESD. INTERVENTION: ME with NBI for cancers with unclear margins by CE. MAIN
      OUTCOME MEASUREMENTS: The rate of successful delineation by ME with NBI for
      cancers that had demonstrated unclear margins using CE. RESULTS: The proportion
      of cancers showing unclear margins using CE was 18.9% (66/350). Of these, 62 of
      66 cancers were examined using ME with NBI, with the entire margins successfully
      delineated in 72.6% (45/62) of the lesions that had shown unclear margins using
      CE. The success rate was 0% for undifferentiated cancers, significantly lower
      than that for differentiated lesions (P < .00001). LIMITATIONS: Even by using ME
      with NBI, endoscopic delineation remains difficult for undifferentiated lesions.
      CONCLUSIONS: ME with NBI is an excellent modality for identifying the entire
      margin of early gastric cancers, when the margins are unclear using CE.

PMID- 22136773
TI  - Obesity as a risk factor for sedation-related complications during propofol
      mediated sedation for advanced endoscopic procedures.
AB  - BACKGROUND: There are limited data on the safety of anesthesia-assisted endoscopy
      by using propofol-mediated sedation in obese individuals undergoing advanced
      endoscopic procedures (AEPs). OBJECTIVE: To study the association between obesity
      (as measured by body mass index [BMI]) and the frequency of sedation-related
      complications (SRCs) in patients undergoing AEPs. DESIGN: Prospective cohort
      study. SETTING: Tertiary referral center. PATIENTS: A total of 1016 consecutive
      patients undergoing AEPs (BMI <30, 730 [72%]; 30-35, 159 [16%]; >35, 127 [12%]).
      INTERVENTION: Monitored anesthesia sedation with propofol alone or in combination
      with benzodiazepines and/or opioids. MAIN OUTCOME MEASUREMENTS: SRCs, airway
      maneuvers (AMs), hypoxemia, hypotension requiring vasopressors, and early
      procedure termination were compared across 3 groups. RESULTS: There were 203 AMs
      in 13.9% of patients, hypoxemia in 7.3%, need for vasopressors in 0.8%, and
      premature termination in 0.6% of patients. Increasing BMI was associated with an
      increased frequency of AMs (BMI <30, 10.5%; 30-35, 18.9%; >35-26.8%; P < .001)
      and hypoxemia (BMI <30, 5.3%; 30-35, 9.4%; >35, 13.4%; P = .001); there was no
      difference in the frequency of need for vasopressors (P = .254) and premature
      termination of procedures (P = .401). On multivariable analysis, BMI (odds ratio
      [OR] 2.0; 95% CI, 1.3-3.1), age (OR 1.1; 95% CI, 1.0-1.1), and American Society
      of Anesthesiologists class 3 or higher (OR 2.4; 95% CI, 1.1-5.0) were independent
      predictors of SRCs. In obese individuals (n = 286), there was no difference in
      the frequency of SRCs in patients receiving propofol alone or in combination (P =
      .48). LIMITATIONS: Single tertiary center study. CONCLUSIONS: Although obesity
      was associated with an increased frequency of SRCs, propofol sedation can be used
      safely in obese patients undergoing AEPs when administered by trained
      professionals.

PMID- 22136776
TI  - Single-operator cholangioscopy-guided laser lithotripsy in patients with
      difficult biliary and pancreatic ductal stones (with videos).
AB  - BACKGROUND: Scant data exist on the utility of the holmium:yttrium-aluminum
      garnet laser for the treatment of biliary or pancreatic duct stones. OBJECTIVE:
      To evaluate the efficacy and safety of fiberoptic probe and catheter system
      guided holmium laser lithotripsy of difficult biliary and pancreatic duct stones.
      DESIGN: Prospective study. SETTING: Tertiary-care referral center. PATIENTS: This
      study involved 64 patients who underwent holmium laser stone fragmentation.
      INTERVENTION: A total of 64 patients (60 bile duct stones, 4 pancreatic duct
      stones) underwent endoscopic retrograde stone fragmentation with a holmium laser
      and a fiberoptic probe and catheter system. The inclusion criterion for bile duct
      stones was stones not amenable to retrieval by mechanical lithotripsy and/or
      balloon sphincteroplasty or standard techniques. Pancreatic duct stones included
      in this study were not amenable to removal by stone retrieval basket or balloon.
      MAIN OUTCOME MEASUREMENTS: Rates of ductal clearance and procedural
      complications. RESULTS: All 64 patients had successful fragmentation of biliary
      and pancreatic duct stones with the holmium laser. Fifty of 60 patients (83.3%)
      had complete biliary duct clearance after a single session; 10 patients required
      an additional session. All pancreatic duct stones were fragmented in a single
      session. Mean duration of ERCP sessions was 45.9 minutes (range 30-90 minutes).
      Complications were mild and were encountered in 13.5% of patients; fever (n = 3),
      transient abdominal pain (n = 4), and biliary stricture (n = 1). LIMITATIONS: No
      comparative treatment group. CONCLUSION: The fiberoptic probe and catheter system
      facilitates transpapillary access for holmium laser fragmentation of difficult
      biliary and pancreatic duct stones. The technique is safe and highly effective
      for single-setting duct clearance. Complications are minimal and transient.

PMID- 22136777
TI  - The role of capsule endoscopy in patients with nonresponsive celiac disease.

PMID- 22136778
TI  - Clinical outcomes and factors related to resectability and curability of EMR for
      early colorectal cancer.
AB  - BACKGROUND: EMR has emerged as an alternative therapeutic option for selected
      cases of early colorectal cancer (ECC). However, the factors associated with
      resectability and curability of EMR for ECC remain unknown. OBJECTIVE: To
      investigate clinical outcomes and factors related to resectability and curability
      in ECC cases treated with EMR. DESIGN: Retrospective study. SETTING: Tertiary
      care academic medical center. PATIENTS: This study involved all patients in whom
      EMR was performed for ECC at Severance Hospital between March 1997 and August
      2007. A total of 236 cases of ECC occurring in 231 patients (66.2% men) were
      enrolled. INTERVENTION: EMR. Curative surgical resection and lymph node
      dissection were used in cases that were incompletely cured by EMR. MAIN OUTCOME
      MEASUREMENTS: Resectability, curability, and recurrence. RESULTS: Complete cure
      was achieved for 162 lesions (68.6%). Of the remaining 74 cases (31.4%), 69
      (29.2%) were incompletely cured, and the other 5 (2.1%) had an undetermined
      resection status and ultimately required supplementary surgical resection for
      curative treatment. Location on the right side of the colon, piecemeal resection,
      and submucosal carcinoma were independently associated with incomplete resection,
      whereas depressed tumor type was independently related to incomplete cure. Among
      the ECC cases completely cured by EMR and followed for more than a year (n =
      118), local recurrence was observed in one case (0.8%) during the median follow
      up period of 39.4 months (range 12.4-123.1 months). LIMITATIONS: Single-center,
      retrospective study. CONCLUSION: Our data show that EMR is feasible and could be
      an effective option for treatment of ECC if the technique is applied with the
      appropriate indications.

PMID- 22136779
TI  - Nitrous oxide for analgesia in colonoscopy without sedation.
AB  - BACKGROUND: Colonoscopy is associated with pain and discomfort, and intravenous
      analgesics and sedatives are widely used. There are several disadvantages
      regarding this practice, including risk of complications, resources demanded, and
      amnesia after sedation. In spite of promising results in previous studies,
      nitrous oxide is rarely used at endoscopy centers around the world. OBJECTIVE: To
      investigate the efficiency of nitrous oxide versus placebo as an analgesic during
      colonoscopy without sedation. DESIGN: A double-blind, randomized, placebo
      controlled trial. SETTING: The endoscopy unit at Oslo University Hospital
      Rikshospitalet, Oslo, Norway, between June 2006 and May 2008. PATIENTS: This
      study involved patients undergoing elective colonoscopy. INTERVENTION: Patients
      inhaled nitrous oxide or placebo on demand. MAIN OUTCOME MEASUREMENTS: The
      participants filled in a questionnaire regarding their experiences with the
      examination. Pain was graded from 1 (no pain) to 4 (severe pain). RESULTS: We
      recruited 199 patients. We randomized 97 patients to the nitrous oxide group and
      102 to the control group. The groups were comparable regarding demographic
      factors. Median patient-reported pain was 2 in both the nitrous oxide group and
      the control group (interquartile range 2-3 in both groups). Additional sedatives
      and analgesics were given equally often and in similar doses in both groups. No
      side effects related to administration of nitrous oxide were reported.
      LIMITATIONS: The questionnaire was returned by 76% of the patients. The study gas
      was given on demand, not continuously. CONCLUSION: Nitrous oxide given
      intermittently is not an effective substitution for intravenous on-demand
      sedation and analgesics in the setting of colonoscopy without sedation.

PMID- 22136780
TI  - When to call the anesthesiologist for assistance with sedation.

PMID- 22136781
TI  - Endoscopic management of colonoscopic perforations (with videos).

PMID- 22136783
TI  - Look before you eat: hazards of grilling.

PMID- 22136782
TI  - The efficacy of endoscopic triamcinolone injection for the prevention of
      esophageal stricture after endoscopic submucosal dissection.
AB  - BACKGROUND: Use of endoscopic submucosal dissection (ESD) for management of
      widespread superficial esophageal carcinomas may be complicated by the
      development of severe strictures, which may require serial treatment with
      endoscopic balloon dilatation (EBD). OBJECTIVE: The goal of this study was to
      determine the efficacy of endoscopic triamcinolone injection (ETI) for the
      prevention of stricture formation after ESD. DESIGN: Case series. SETTING:
      Tertiary-care referral center. PATIENTS: A total of 41 consecutive patients who
      had a semi-circumferential mucosal defect that arose after ESD for superficial
      esophageal squamous cell carcinomas were enrolled in this study. INTERVENTIONS:
      EBD and ETI. MAIN OUTCOME MEASUREMENTS: Incidence of stricture and frequency of
      required EBD. RESULTS: ETI was performed in one group of patients (study group, n
      = 21) but not in the other (control group, n = 20). The incidence of stricture
      was significantly lower in the study group (19.0%) than in the control group
      (75.0%; P < .001). The number of required EBDs was also lower in the study group
      (mean, 1.7; range, 0-15) than in the control group (mean, 6.6; range 0-20). There
      were no side effects or complications associated with ETI. LIMITATIONS:
      Nonrandomized study design and small number of patients in a single endoscopic
      center. CONCLUSIONS: This study suggests that ETI is safe and effective for the
      prevention of esophageal stricture in patients undergoing ESD for superficial
      esophageal squamous cell carcinomas.

PMID- 22136784
TI  - A bullet to the head.

PMID- 22136785
TI  - Cyst fluid carcinoembryonic antigen in the investigation of cystic neuroendocrine
      tumors of the pancreas.

PMID- 22136786
TI  - Endoscopic management of GI fistulae with the over-the-scope clip system (with
      video).

PMID- 22136787
TI  - Pill-related esophageal intramural dissection treated by an endoscopic procedure.

PMID- 22136789
TI  - Pancreaticobiliary complications after composite visceral transplantation:
      incidence, risk, and management strategies.

PMID- 22136790
TI  - Does removal of prophylactic pancreatic stents induce acute pancreatitis?

PMID- 22136791
TI  - Sufficient sphincterotomy or rescue for impacted entrapped bile stones.

PMID- 22136794
TI  - Somatoform disorder after conscious sedation.

PMID- 22136795
TI  - Accumulative gene integration into a pre-determined site using Cre/loxP.
AB  - Site-specific gene recombination systems, such as Cre/loxP, have been used for
      genetic modification of cells and organisms in both basic and applied research.
      We previously developed an accumulative gene integration system (AGIS), in which
      target gene cassettes could be repeatedly integrated into a pre-determined site
      on a plasmid or cellular genome by recombinase-mediated cassette exchange (RMCE),
      using Cre and mutated loxPs. In the present study, we designed a simplified AGIS.
      For gene integration into a target site, the previous system used two loxP sites
      in the acceptor DNA, whereas the new system uses a single loxP site. The gene
      integration reactions were repeated four times in vitro using Cre protein and
      specific plasmids. The expected integration reactions mediated by Cre occurred at
      the loxP sites, resulting in integration of four target genes. The system was
      also used for genomic integration of reporter genes using Chinese hamster ovary
      (CHO) cells. The reporter genes were efficiently introduced into the CHO genome
      in a Cre-dependent manner, and transgene expression was detected after the
      integration reaction. The expression levels of the reporter genes were enhanced,
      corresponding to the increase of transgene copy number. Recombinase-mediated AGIS
      provides a useful tool for the modification of cellular genomes.

PMID- 22136796
TI  - Development of a heat-processing method for koji to enhance its antioxidant
      activity.
AB  - We developed a heat-processing method to enhance the antioxidant activity of
      koji. The superoxide anion scavenging activity (SOSA) and oxygen radical
      absorbance capacity (ORAC) of heat-processed koji (HP-koji) at 55  degrees C for
      7 days were 4.9 times and 4.2 times, respectively, those of unheated koji. These
      results showed that heat processing effectively enhances the antioxidant activity
      of koji. Analysis of the antioxidant activities of koji subjected to a range of
      temperatures (45-75  degrees C) revealed that the SOSA is enhanced by heating at
      higher temperatures, which might be catalyzed by Maillard reaction, whereas the
      ORAC was enhanced by heating at lower temperatures, which might be catalyzed by
      an enzymatic reaction. Assuming these enhancements in antioxidant activities are
      contributed by both Maillard and enzyme reactions, we hypothesized that the
      antioxidant activity of HP-koji could be more effectively amplified by heating at
      a higher temperature after the progression of the enzymatic reaction at a
      moderate temperature. Therefore, we evaluated the effect of heating of koji in a
      stepwise manner, first at 55  degrees C for 2 days and then at 75  degrees C for
      5days. The antioxidant activities of stepwise-heated HP-koji were higher than
      those of koji heated at either 55  degrees C or 75  degrees C. The SOSA and ORAC
      of stepwise-heated HP-koji were 94 times and 6 times, respectively, those of
      unheated koji. This result suggests that enzymatic reaction followed by Maillard
      reaction can effectively enhance the antioxidant activity of HP-koji. Thus, we
      developed a novel heat-processing method to enhance the antioxidant activity of
      koji.

PMID- 22136797
TI  - Correlation and discriminant analysis between clinical, endoscopic, thoracic X
      ray and bronchoalveolar lavage fluid cytology scores, for staging horses with
      recurrent airway obstruction (RAO).
AB  - As recurrent airway obstruction (RAO) is progressive and as medical history is
      frequently unknown by owners, it's important to suggest a score model to
      characterize RAO stages for a more accurate diagnosis and treatment. The authors
      correlated clinical (CS), endoscopic (ES), thoracic X-ray (XRS) and
      bronchoalveolar lavage fluid (BALFS) scores in horses with RAO, in an attempt to
      establish relevance of each factor's contribution for the characterization of RAO
      stages and to suggest a staging method. Thirty horses with RAO and ten healthy
      controls were studied. Pearson correlation coefficients were determined between
      CS, ES, XRS and BALFS. Only significant correlation coefficients (>0.60) were
      considered. One way variance analyses were used to compare the two groups. A
      discriminant analysis model was adjusted on the RAO staging method suggested.
      There was a significant correlation coefficient between the CS cough, nostril
      flare and abdominal lift, all the mucus ES (0.61-0.84), the XRS interstitial
      pattern, bronchial radiopacity and thickening and tracheal thickening (0.67-0.78)
      and the BALFS neutrophil percentages (0.63-0.84). These variables (e.g., cough)
      which presented a significant correlation coefficient were considered relevant
      and chosen for a score model to characterize RAO stages. The ten healthy controls
      were attributed stage 0 and the 30 RAO horses were attributed stages 1 (4
      horses), 2 (7 horses), 3 (10 horses) and 4 (9 horses). There was also a
      significant correlation coefficient between all the relevant variables and the
      RAO stage (0.61-0.89). Furthermore, discriminant analysis of the RAO staging
      method showed 92.5% of original grouped cases and 85.0% of cross-validated
      grouped cases correctly classified, having confirmed major contribution of the
      same variables that had significant correlation coefficients. Even though further
      confirmation by lung functional testing is desirable, the significant correlation
      between relevant variables and RAO stage and the results of RAO staging
      discriminant analysis support the suggestion of our score model for the
      characterization of RAO stages.

PMID- 22136798
TI  - Aromatase inhibitors in the treatment of recurrent ovarian granulosa cell tumors:
      brief report and review of the literature.
AB  - Granulosa cell tumors are ovarian sex cord stromal cancers that are unique for
      their indolent nature and late recurrence. Standard treatment regimens utilized
      include surgery, chemotherapy, and radiotherapy. However, hormonal suppression
      with aromatase inhibitors, which have shown promising results, may be a viable
      alternative to these modalities. We present a heavily pre-treated, multi-operated
      patient who experienced significant tumor shrinkage following treatment with an
      aromatase inhibitor for her recurrent granulosa cell tumor.

PMID- 22136799
TI  - Spectral analysis of heart rate variability with the autoregressive method: what
      model order to choose?
AB  - This work assessed the influence of the autoregressive model order (ARMO) on the
      spectral analysis of the heart rate variability (HRV). A sample of 68 R-R series
      obtained from digital ECG records of young healthy adults in the supine position
      was used. Normalized spectral indexes for each ARMO were compared by Friedman
      test followed by the Dunn's procedure and statistical significance was set at
      P<0.05. The results showed that the AR method using orders from 9 to 25 produces
      normalized spectral parameters statistically similar and, hence, the algorithms
      commonly employed to estimate optimum order are not mandatory in this case.

PMID- 22136800
TI  - [Trade-off between formal and informal care in Europe].
AB  - OBJECTIVE: To study the relationship between formal and informal care for the
      dependent population in a number of European countries. METHOD: Data from the
      Survey of Health, Aging and Retirement in Europe for 2004 were used and a
      bivariate probit model was estimated. Unlike other studies, the present analysis
      includes the institutional features of the various long-term care systems, in
      addition to the demographic, health and environmental characteristics of the
      individual receiving care. RESULTS: A significant correlation was found between
      the two options, which reveals that, conditional on receiving care, there was a
      preference for the combination of both types of care. The results show the
      importance of health status and living arrangements for defining the combination
      of formal and informal care. There were substantial differences in the likelihood
      of the two types of care among European countries. A notable finding was the
      importance of informal care in Spain in comparison with other countries.
      CONCLUSIONS: The probability of receiving formal or informal care is higher in
      countries where families have a legal obligation to look after dependent
      relatives and where institutionalization rates are higher. This finding should be
      considered in the design of long-term care policies. Therefore, to control growth
      of public expenditure and, at the same time, improve caregiver satisfaction,
      policies that combine distinct formal services should be promoted over the
      implementation of care allowances.

PMID- 22136801
TI  - Oesophageal cancer treatment in a tertiary referral hospital evaluated by
      indicators for quality of care.
AB  - BACKGROUND: Studies on quality of care for oesophageal cancer patients usually
      include only traditional outcome parameters. The aim of the study was to address
      quality of care in a broader perspective. METHODS: Between 2003 and 2008, 821
      oesophageal cancer patients were referred to our institute. Indicators to measure
      quality of care (i.e., process and outcome measures) were defined and comparisons
      between two time periods were made. RESULTS: 335 patients came for a second
      opinion only, 382 patients received palliative treatment and 104 (13%) patients
      underwent potentially curative treatment. The median time between the first
      hospital visit and start of treatment decreased from 24 days in period I to 18
      days in period II (P = 0.03). Of patients who underwent potentially curative
      treatment, 81% in period I and 86% in period II were discussed during a weekly
      multidisciplinary meeting (P = 0.54). Compliance with the national guideline was
      comparable in both periods (84% vs. 80%, P = 0.27). There were non-significant
      improvements in completion of chemoradiation (85% vs. 91%), postoperative
      complication rates (57% vs. 33%) and 3-year survival (40% vs. 46%). CONCLUSION:
      By evaluating different dimensions of health care quality, we have identified
      which steps in the multidisciplinary care path need more attention in order to
      raise the whole level of care. Efforts for improvement should focus primarily on
      process measures rather than on outcome measures for which high-quality standards
      are already met.

PMID- 22136802
TI  - Layer-by-layer films composed of poly(allylamine) and insulin for pH-triggered
      release of insulin.
AB  - Layer-by-layer (LbL) thin films containing insulin were prepared by alternately
      depositing insulin and poly(allylamine hydrochloride) (PAH) onto a solid surface
      at pH 7.4. The deposition behavior of the LbL films was studied using a quartz
      crystal microbalance, UV-vis absorption spectrometer, zeta-potential analyzer,
      and an atomic force microscope. The insulin-containing LbL films were stable in
      neutral pH media, but the films decomposed in solutions at pH 5.0 or lower. The
      decomposition of the LbL films can be rationalized on the basis of the loss of
      electrostatic interactions between insulin and PAH due to a shift in the net
      electric charge of insulin from negative to positive in acidic media. The films
      also decomposed to some extent in media at pH 9.0 and 10. A circular dichroism
      analysis showed that insulin retained its original conformation when released
      from LbL film into acidic solutions.

PMID- 22136803
TI  - Diabetes mellitus effect on rat corneal dielectric properties.
AB  - In the course of the study, we carried out a dielectric examination to determine
      the effect of diabetes mellitus on the rat corneal function. Measurements were
      performed over the frequency range of 500 Hz-100 kHz in air and at the
      temperatures from 25 to 150 degrees C. The frequency dependencies of the loss
      tangent for the healthy and the diabetic cornea exhibit two peaks at 2 kHz and 16
      kHz in the alpha-dispersion region. The amplitude of these both peaks is smaller
      for the diabetic cornea than that for the healthy one. The temperature
      dependencies of the loss tangent for the healthy and the diabetic cornea reveal
      beta-relaxation in the range of 30-70 degrees C and 50-90 degrees C,
      respectively. The present study exhibits that the dielectric spectroscopy is
      useful in detection of the effect of diabetes mellitus on the corneal molecular
      behavior.

PMID- 22136804
TI  - Application of albumin-grafted scaffolds to promote neocartilage formation.
AB  - This study investigates the capacity of albumin-grafted biomaterials as tissue
      engineering scaffolds to regenerate cartilaginous components. Porcine knee
      chondrocytes were seeded and cultivated in porous ternary matrix consisting of
      polyethylene oxide, chitin, and chitosan with surface albumin. The results
      revealed that the quantity of albumin did not affect the viability of porcine
      knee chondrocytes in the constructs. However, a high grafting concentration of
      albumin favored the adhesion of porcine knee chondrocytes on the scaffolding pore
      surface. After cultivation over 4 weeks, an increase in the concentration of
      albumin enhanced the quantities of porcine knee chondrocytes, glycosaminoglycans,
      and collagen in the constructs. The histological staining of porcine knee
      chondrocytes showed an active chondrocytic growth in the albumin-grafted
      constructs. In addition, the safranin-O staining indicated that the surface
      albumin could stabilize the secretion of glycosaminoglycans. Moreover, the
      immunochemical staining against type II collagen exhibited a regular production
      of collagen by phenotypic porcine knee chondrocytes in the constructs. Albumin
      grafted polyethylene oxide/chitin/chitosan scaffolds can be a promising
      biomimetic substrate in neocartilage formation.

PMID- 22136805
TI  - Modulation of efflux proteins by electromagnetic field for delivering
      azidothymidine and saquinavir into the brain.
AB  - An exposure to an electromagnetic field (EMF) has been shown to enhance the
      membrane permeability of endothelial cells. This study investigates the effect of
      EMF on the modulation of P-glycoprotein (P-gp) and multidrug resistance
      associated protein (MRP) for delivering saquinavir (SQV) and azidothymidine
      (AZT). To assess the transport of SQV and AZT, an EMF and P-gp/MRP (transport
      protein) inhibitors were employed to stimulate confluent human brain
      microvascular endothelial cells (HBMECs) with the regulation of human astrocytes.
      SQV at 40 MUM and AZT at 300 MUM were acceptable dosages for the viability of
      HBMECs. Under an EMF, verapamil showed a higher ability to elevate the permeation
      across the blood-brain barrier (BBB) than probenecid during treating with SQV.
      The reverse was true during treating with AZT. After an exposure to an EMF and
      administration of SQV and AZT, P-gp and MRP1 localized on the luminal side of
      HBMECs, exhibiting polar characteristics of the cell membranes. The synergetic
      effect of an EMF exposure and efflux protein inhibition can be promising in
      delivering antiretroviral drugs across the BBB.

PMID- 22136806
TI  - Prematurity does not markedly affect intestinal sensitivity to endotoxins and
      feeding in pigs.
AB  - Preterm neonates show enhanced sensitivity to nutrient maldigestion and bacteria
      mediated gut inflammatory disorders, such as necrotising enterocolitis (NEC). We
      hypothesised that preterm birth increases the sensitivity of intestinal nutrient
      absorption to endotoxins and that feeding after birth reduces this response.
      Hence, we investigated the postnatal development of nutrient digestive and
      absorptive capacity in the preterm and term pig intestine, and its responsiveness
      to endotoxins. Pigs were delivered by caesarean section at preterm (n 20) or term
      (n 17) gestation, and the small intestine was collected at birth or after 2 d of
      colostrum feeding, followed by ex vivo stimulation with lipopolysaccharide
      endotoxins and mixed gut contents collected from pigs with NEC. Brush border
      enzyme activities were reduced in newborn preterm v. term pigs (39-45 %
      reduction, P < 0.05), but normalised after 2 d of feeding. Ex vivo leucine and
      glucose uptake increased with prenatal age. Bacterial stimulation reduced the
      nutrient uptake similarly at birth and after 2 d in preterm and term pigs (23-41
      % reduction, P < 0.05), whereas IL-6 and TNF-alpha expression was stimulated only
      at birth. Toll-like receptor-4 expression increased markedly at day 2 for preterm
      and term pigs (22-33-fold, P < 0.05) but with much lower expression levels in
      newborn preterm pigs (approximately 95 %, P < 0.01). In conclusion, digestive and
      absorptive functions mature in the prenatal period, but are similarly affected by
      postnatal feeding and bacterial exposure in both preterm and term pigs. Nutrient
      maldigestion may contribute to NEC development, while a prematurity-related hyper
      responsiveness to endotoxins could be less important, at least in pigs.

PMID- 22136807
TI  - Short-term cast immobilisation is effective in reducing lesion propagation in a
      surgical model of equine superficial digital flexor tendon injury.
AB  - REASONS FOR PERFORMING THE STUDY: Larger superficial digital flexor tendon (SDFT)
      injuries have a poorer prognosis than smaller lesions. During the inflammatory
      phase enlargement of the initial lesion is frequently noted, with biomechanical
      loading being recently proposed to play an important role. OBJECTIVES: To
      evaluate the effect of lower limb cast immobilisation on tendon lesion
      propagation in an equine model of surgically induced SDFT injury. METHODS: Core
      lesions were surgically induced in both front SDFTs of 6 young mature horses. At
      the end of surgery, one leg was randomly placed in a lower limb cast and the
      other leg (control) was bandaged for 10 days. Computerised ultrasonographic
      tissue characterisation performed at Days 10, 15, 21, 28, 35 and 42 allowed
      measurement of lesion length (cm) and width (expressed as a percentage of whole
      tendon cross-section). On Day 42 horses were subjected to euthanasia and both
      SDFTs were sectioned every centimetre to assess the lesion length
      macroscopically. Statistics were performed to compare cast vs. control legs with
      significance set at P<0.05. RESULTS: When all time points were combined, lesion
      length was 19% shorter (P<0.0001) and lesion width 57% smaller (P = 0.0002) in
      the cast legs (6.13 +/- 0.12 cm; 6.90 +/- 0.64%) than in the control legs (7.30
      +/- 0.21 cm; 10.85 +/- 1.22%). On Day 42 the lesion length on macroscopic
      evaluation was 19% shorter (P = 0.04) in the cast (7.00 +/- 0.36 cm) than in the
      control legs (8.33 +/- 0.33 cm). CONCLUSIONS: Cast immobilisation for 10 days
      effectively reduced lesion propagation (length and width) compared to bandaging
      in an in vivo model of artificially-induced tendon lesions. POTENTIAL RELEVANCE:
      A short period of cast immobilisation during the early phase of tendon healing
      may be an easy and cost-effective way to reduce the initial enlargement of lesion
      size and hence to improve prognosis.

PMID- 22136808
TI  - Assessment of food offerings and marketing strategies in the food-service venues
      at California Children's Hospitals.
AB  - OBJECTIVE: Marketing strategies and food offerings in hospital cafeterias can
      impact dietary choices. Using a survey adapted to assess food environments, the
      purpose of this study was to assess the food environment available to patients,
      staff, and visitors at the food-service venues in all 14 California children's
      hospitals. METHODS: We modified a widely-used tool to create the Nutritional
      Environment Measures Survey for Cafeterias (NEMS-C) by partnering with a hospital
      wellness committee. The NEMS-C summarizes the number of healthy items offered,
      whether calorie labeling is present, if there is signage promoting healthy or
      unhealthy foods, pricing structure, and the presence of unhealthy combination
      meals. The range of possible scores is zero (unhealthy) to 37 (healthy). We
      directly observed the food-service venues at all 14 tertiary care children's
      hospitals in California and scored them. RESULTS: Inter-rater reliability showed
      89% agreement on the assessed items. For the 14 hospitals, the mean score was
      19.1 (SD = 4.2; range, 13-30). Analysis revealed that nearly all hospitals
      offered diet drinks, low-fat milk, and fruit. Fewer than one-third had nutrition
      information at the point of purchase and 30% had signs promoting healthy eating.
      Most venues displayed high calorie impulse items such as cookies and ice cream at
      the registers. Seven percent (7%) of the 384 entrees served were classified as
      healthy according to NEMS criteria. CONCLUSIONS: Most children's hospitals' food
      venues received a mid-range score, demonstrating there is considerable room for
      improvement. Many inexpensive options are underused, such as providing
      nutritional information, incorporating signage that promotes healthy choices, and
      not presenting unhealthy impulse items at the register.

PMID- 22136809
TI  - Respiratory allergy to fungi in Barcelona, Spain: clinical aspects, diagnosis and
      specific treatment in a general allergy unit.
AB  - BACKGROUND: The importance of hypersensitivity to fungal allergens is a
      relatively unknown and somewhat controversial subject. METHODS: An open
      prospective study was carried out in just one centre to determine the clinical
      and epidemiological characteristics as well as the diagnostic usefulness of skin
      prick and conjunctiva provocation tests, associated with total and specific IgE
      determination in two groups of patients, one of which was monosensitised to fungi
      and the other of which had multiple sensitisations, including fungi. RESULTS:
      Rhinitis, exclusive or associated with asthma, was the main consultation cause
      (88% in monosensitised patients). Severe asthma was rarely found. In the
      polysensitised group, 64% were simultaneously allergic to moulds and mites.
      Alternaria alternata was the most common sensitising fungus, although a
      considerable number of cases were associated with other species such as
      Cladosporium, Penicillium and/or Aspergillus. The skin prick test gave the
      highest sensitivity and specificity. In 67% of the cases, the specific IgE was
      found between classes 3 and 4. The conjunctival provocation test was an innocuous
      and highly useful method for verifying the diagnosis and determining the degree
      of clinical sensitisation. A large number of patients exclusively allergic to
      fungi received specific immunotherapy, and it was generally well tolerated.
      CONCLUSIONS: This protocolised study shows the importance of Alternaria and other
      fungi sensitisations in rhinitis alone or associated with asthma. Combined
      diagnosis of prick test, specific IgE and conjunctiva provocation test is very
      useful for deciding specific immunotherapy.

PMID- 22136810
TI  - Cancer patient pathways in Denmark as a joint effort between bureaucrats, health
      professionals and politicians--a national Danish project.
AB  - In 2007 and 2008 Danish Cancer Patient Pathways for 32 cancer types were
      developed and afterwards implemented on a national scale. Often bureaucrats,
      health professionals and politicians look upon the health sector in different
      ways and work independent of each other. In Denmark, as indeed internationally,
      patient pathways are frequently developed solely by health professionals and the
      consequence may be major difficulties in implementing the pathways on a national
      scale. In this article we describe how national Danish Cancer Patient Pathways
      were developed with a consensus seeking model and the impact it has had on the
      health system. The model used in Denmark ensured involvement and cooperation
      between bureaucrats, health professionals and politicians and afterwards a
      successful national implementation. The Cancer Patient Pathways has significantly
      reduced waiting times which is thought to increase survival. This experience
      gives important input to the continuous challenges on how to implement evidence
      based medicine on a national scale and stipulates a model for this process.

PMID- 22136811
TI  - Scanning the horizon: development and implementation of an early awareness system
      for anticancer drugs in Austria.
AB  - BACKGROUND: Due to increasing expenditures for cancer therapies, an instrument
      was needed in Austria to facilitate the evidence-based use of new anticancer
      drugs and to pre-estimate their financial implications. OBJECTIVES: To describe
      and analyse the development and implementation of a Horizon Scanning System (HSS)
      in Austria that allows for the evaluation of new anticancer drugs before their
      routine introduction into clinical practice in order to inform decision-makers.
      METHODS: Common stages involved in HSSs were identified by a literature review
      and in cooperation with experts. A first concept for an HSS in Oncology was
      developed and piloted, and further adjustments were made after several feedback
      rounds with experts in oncology. RESULTS: To specifically tailor the five common
      stages of HSSs to the needs of our HSS, a continually evolving process was
      required. Now, 21 information sources are regularly scanned, the information is
      retrieved and extracted in a standardised format, and only anticancer drugs in
      phase III are included and prioritised by a team of eight experts. Since the HSS
      in Oncology was implemented as a standard practice, 19 assessments on novel
      cancer therapies with likely therapeutic and/or financial impacts have been
      published. CONCLUSIONS: The successful implementation of an HSS necessitates a
      repetitive cycle of adjustments in order to meet the objectives set by the
      individual HSS.

PMID- 22136812
TI  - From evidence assessments to coverage decisions?: the case example of glinides in
      Germany.
AB  - In Germany, coverage decisions in the statutory health insurance (SHI) system are
      based on the principles of evidence-based medicine. Recently, an evidence
      assessment by the Institute for Quality and Efficiency in Health Care (IQWiG) of
      the oral antidiabetics of the glinide class showed that their long-term benefit
      is not proven. Accordingly, the responsible Federal Joint Committee (G-BA)
      decided to exclude glinides from prescription in the SHI system. This was,
      however, objected to by the Ministry of Health, which is charged with legal
      supervision. We use this case to illustrate the path from evidence assessments to
      coverage decisions in Germany against the background of the latest health reform,
      which has changed the legal requirements for evidence assessments and the ensuing
      coverage decisions.

PMID- 22136813
TI  - How innovative are pharmaceutical innovations?: the case of medicines financed
      through add-on payments outside of the French DRG-based hospital payment system.
AB  - OBJECTIVE: To analyze the characteristics of inpatient medicines placed on the
      list of innovative high-cost medicines funded in addition to DRG-based payment,
      and to identify whether they really are innovative and/or high-cost. METHODOLOGY:
      The medicines placed on the list of innovative and high-cost medicines were
      analyzed on the basis of criteria describing their innovative nature and cost.
      They were categorized as innovative and high-cost, only high-cost, only
      innovative and neither innovative nor high-cost. RESULTS: Among the medicines
      financed in addition to DRG-based payment, 25.5% were classified as innovative
      and high-cost, 23.5% only high-cost, 22.9% only innovative and 28.1% neither
      innovative nor high-cost. CONCLUSIONS: The list of innovative and high-cost
      medicines contains medicines other than innovative and high-cost medicines.
      Stricter criteria for placing medicines on this list should be considered in
      order to limit the increase in expenditure.

PMID- 22136814
TI  - Measurements and standards for bulk-explosives detection.
AB  - Recent years have seen a dramatic expansion in the application of radiation and
      isotopes to security screening. This has been driven primarily by increased
      incidents involving improvised explosive devices as well as their ease of
      assembly and leveraged disruption of transportation and commerce. With global
      expenditures for security-screening systems in the hundreds of billions of
      dollars, there is a pressing need to develop, apply, and harmonize standards for
      x-ray and gamma-ray screening systems used to detect explosives and other
      contraband. The National Institute of Standards and Technology has been
      facilitating the development of standard measurement tools that can be used to
      gauge the technical performance (imaging quality) and radiation safety of systems
      used to screen luggage, persons, vehicles, cargo, and left-behind objects. After
      a review of this new suite of national standard test methods, test objects, and
      radiation-measurement protocols, we highlight some of the technical trends that
      are enhancing the revision of baseline standards. Finally we advocate a more
      intentional use of technical-performance standards by security stakeholders and
      outline the advantages this would accrue.

PMID- 22136815
TI  - Development of k0-INAA standardization method by neutron activation with Am-Be
      source.
AB  - The k(0)-standardization method on the (241)Am-Be isotopic neutron source has
      been studied and developed. In this paper, the characteristics of the neutron
      spectrum in an isotropic neutron field of (241)Am-Be isotopic neutron sources was
      experimentally determined by dual monitor method using measured cadmium ratios of
      (197)Au(n, gamma)(198)Au and (98)Mo(n, gamma)(99)Mo(beta(-))(99m)Tc reactions.
      Application of the k(0)-standardization method for the determination of elemental
      concentrations such as Al, Mn and Na in cement is carried out as well. The
      obtained results are in agreement with other analyses.

PMID- 22136816
TI  - Papillary carcinoma of the thyroid: balancing principles of oncology with
      emerging technology.

PMID- 22136817
TI  - Molecular pathways associated with mortality in papillary thyroid cancer.
AB  - BACKGROUND: A better understanding of the molecular mechanisms involved in
      papillary thyroid cancer (PTC)-associated adverse outcome is needed to manage
      these patients effectively. Our objectives were to identify molecular pathways
      associated with unfavorable features and outcomes in patients with PTC. METHODS:
      We performed genome-wide expression (GWE) analysis in 64 human tissue samples
      affected by PTC. Clinical, pathologic, and microarray data were analyzed to
      identify differentially expressed genes and pathways associated with unfavorable
      outcomes. Gene set enrichment analysis (GSEA) was used to determine which
      molecular pathways are associated with mortality. RESULTS: GWE analysis
      identified 43, 115, and 40 genes that were significantly differentially expressed
      by gender, tumor differentiation status, and mortality, respectively, with a
      false-discovery rate of <5%. For mortality, GSEA revealed 7 enriched pathways,
      including transfer RNA synthesis, mitochondria and oxidative phosphorylation,
      porphyrin and chlorophyll metabolism, and fatty acid synthesis. Leading-edge
      analysis showed that 341 genes were significantly involved in the enriched
      pathways. Cluster analysis using 100 differentially expressed genes showed
      complete separation of patients by mortality. CONCLUSION: To our knowledge, this
      is the first GWE analysis of PTC and adverse outcomes. We found 11 molecular
      pathways that were significantly associated with mortality resulting from PTC. A
      100-gene signature completely separates patients with and without PTC-associated
      mortality.

PMID- 22136818
TI  - Necroptosis is a novel mechanism of radiation-induced cell death in anaplastic
      thyroid and adrenocortical cancers.
AB  - BACKGROUND: Necroptosis is a recently described mechanism of programmed cellular
      death. We hypothesize that necroptosis plays an important role in radiation
      induced cell death in endocrine cancers. METHODS: Thyroid and adrenocortical
      carcinoma cell lines were exposed to increasing doses of radiation in the
      presence of necroptosis inhibitor Nec-1 and/or apoptosis-inhibitor zVAD. H295R
      cells deficient in receptor interacting protein 1 (RIP1), an essential kinase for
      necroptosis, were used as controls. Survival curves were generated at increasing
      doses of radiation. RESULTS: Nec-1 and zVAD increased cellular survival with
      increasing doses of radiotherapy in 8505c, TPC-1, and SW13. Both inhibitors used
      together had an additive effect. At 6 Gy, 8505c, TPC-1, and SW13 cell survival
      was significantly increased compared to controls by 40%, 33%, and 31% with Nec-1
      treatment, by 53%, 47%, and 44% with zVAD treatment, and by 80%, 70%, and 65%
      with both compounds, respectively (P < .05). H295R showed no change in survival
      with Nec-1 treatment. The radiobiologic parameter quasithreshold dose was
      significantly increased in 8505c, TPC-1, and SW13 cells when both Nec-1 and zVAD
      were used in combination to inhibit necroptosis and apoptosis together, revealing
      resistance to standard doses of fractionated therapeutic radiation. CONCLUSION:
      Necroptosis contributes to radiation-induced cell death. Future studies should
      investigate ways to promote the activation of necroptosis to improve
      radiosensitivity.

PMID- 22136819
TI  - Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia
      virus carrying the human sodium iodide symporter.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is fatal with resistance to
      radiotherapy because of the loss of intrinsic human sodium iodine symporter
      (hNIS). We determined whether vaccinia virus carrying hNIS kills and induces hNIS
      reexpression in ATC cells, facilitating deep-tissue imaging. METHODS: Vaccinia
      virus (GLV-1h153) carrying hNIS was tested against ATC lines for killing and
      replication via cytotoxicity and viral plaque assays. Cellular radiouptake was
      determined using radiouptake assays. GLV-1h153-infected ATC xenografts were
      imaged via (99m)Tc-pertechnetate. RESULTS: GLV-1h153 infected, replicated in, and
      killed all ATC cell lines. GFP expression confirmed viral infection by 24 hours.
      At a multiplicity of infection (MOI) of 1.0, GLV-1h153 reached near 100%
      cytotoxicity in 8305c and FRO by day 5 and 70% in the least sensitive cell line,
      8505c. GLV-1h153-infected ATC cells had a 14-fold increase of hNIS-specific
      radiouptake compared with uninfected control 24 hours after infection at an MOI
      of 1.0. In vivo, GLV-1h153 facilitated imaging of hNIS expression in 8505c tumors
      using (99m)Tc-pertechnetate. CONCLUSION: GLV-1h153 is an effective oncolytic
      agent against ATC. The results show hNIS-specific radiouptake in infected ATC
      cells, facilitating deep-tissue imaging. GLV-1h153 is a promising candidate for
      treatment and imaging, and potentially enhancing susceptibility to radioiodine
      therapy by converting non-hNIS-expressing cells into hNIS-expressing ATC cells.

PMID- 22136820
TI  - A multicenter cohort study of total thyroidectomy and routine central lymph node
      dissection for cN0 papillary thyroid cancer.
AB  - BACKGROUND: The role of routine central lymph node dissection (CLND) for
      papillary thyroid cancer (PTC) remains controversial. The aim of this study was
      to evaluate the impact of routine CLND after total thyroidectomy (TTx) in the
      management of patients with PTC who were clinically node negative at presentation
      with emphasis on stimulated thyroglobulin (Tg) levels and reoperation rates.
      METHODS: This retrospective, multicenter, cohort study used pooled data from 3
      international Endocrine Surgery units in Australia, the United States, and
      England. All study participants had PTC >1 cm without preoperative evidence of
      lymph node disease (cN0). Group A patients had TTx alone and group B had TTx with
      the addition of CLND. RESULTS: There were 606 patients included in the study.
      Group A had 347 patients and group B 259 patients. Stimulated Tg values were
      lower in group B before initial radioiodine ablation (15.0 vs 6.6 ng/mL; P =
      .025). There was a trend toward a lower Tg at final follow-up in group B (1.9 vs
      7.2 ng/mL; P = .11). The rate of reoperation in the central compartment was lower
      in group B (1.5 vs 6.1%; P = .004). The number of CLND procedures required to
      prevent 1 central compartment reoperation was calculated at 20. CONCLUSION: The
      addition of routine CLND in cN0 papillary thyroid carcinoma is associated with
      lower postoperative Tg levels and reduces the need for reoperation in the central
      compartment.

PMID- 22136821
TI  - Prophylactic central compartment neck dissection for papillary thyroid cancer:
      the search for justification continues.

PMID- 22136822
TI  - The effect of vitamin D levels on postoperative calcium requirements, symptomatic
      hypocalcemia, and parathormone levels following parathyroidectomy for primary
      hyperparathyroidism.
AB  - BACKGROUND: Low vitamin D-25 is common in primary hyperparathyroidism but the
      effect of this deficiency on postparathyroidectomy calcium requirements is
      unclear. METHODS: A prospective study was conducted on 4 groups based on
      preoperative vitamin D-25 levels: very low (<20 ng/mL, n = 500); low (21 to 30
      ng/mL, n = 500); normal (>30 ng/mL, n = 500); and supplemented (<25 ng/mL
      supplemented to >40 ng/mL, n = 285). Patients were placed on identical
      postoperative oral calcium regimens, and hypocalcemia symptoms were recorded.
      Total calcium requirements for 2 weeks postoperation were calculated and
      parathormone (PTH) levels were measured for 2-6 months. RESULTS: Mean vitamin D
      levels (ng/mL) for each group were: very low (14.2); low (24.4); normal (38.3);
      and supplemented (16.5 supplemented to 54.3). Postoperative oral calcium
      requirements (in grams) were identical for all groups (18.7, 18.2, and 18.6, and
      19.0, respectively, all P = NS); the incidence and timing of hypocalcemia
      symptoms were nearly identical for all groups: 8.1%, 7.9%, and 7.8% (P = .8).
      Elevated postsurgical PTH was identical (below 8%) and was not influenced by
      vitamin D levels. CONCLUSION: The incidence of hypocalcemic symptoms and the
      postoperative calcium requirements are identical for patients with very low, low,
      normal, or supplemented (high) vitamin D. The incidence of persistently elevated
      PTH postoperatively is also unrelated to preoperative vitamin D levels. Vitamin D
      supplementation from very low to high levels has no clinical benefit.

PMID- 22136823
TI  - Transient increases in intraoperative parathyroid levels related to anesthetic
      technique.
AB  - BACKGROUND: Parathyroid hormone (PTH) secretion is partially regulated by
      circulating catecholamines. We examined the effect of different anesthetic
      techniques on intraoperative PTH (IOPTH) levels in patients undergoing
      parathyroidectomy for primary hyperparathyroidism. METHODS: We prospectively
      studied 132 patients divided into 3 anesthetic cohorts: monitored anesthetic care
      (MAC; n = 45), general anesthesia with laryngeal mask airway (LMA; n = 43), or
      general endotracheal anesthesia (GETA; n = 39). IOPTH levels were drawn before
      induction and at defined intervals postinduction. RESULTS: All anesthetic
      techniques increased IOPTH levels from preinduction to 3 minutes postinduction
      (MAC, 28%; LMA, 45%; GETA, 65%; P < .001). Temporal trends in postinduction IOPTH
      levels were similar in patients receiving general anesthesia, characterized by a
      peak effect at 6 minutes. Using a multivariate logistic regression analysis, GETA
      was >7 times more likely to increase the preinduction IOPTH by >= 50% at 3
      minutes postinduction compared with MAC (P < .0001). Using immediate
      postinduction IOPTH levels in surgical decision making would have led to failed
      surgery in 2 of 6 patients with multiple gland disease receiving GETA.
      CONCLUSION: Preincision IOPTH samples should be drawn before induction to avoid
      incorporation of potentially misleading anesthetic-related IOPTH elevations into
      surgical decision making.

PMID- 22136824
TI  - Normocalcemic parathormone elevation after successful parathyroidectomy: long
      term analysis of parathormone variations over 10 years.
AB  - BACKGROUND: The long-term significance of normocalcemic parathormone elevation
      (NPE) after successful parathyroidectomy for sporadic primary hyperparathyroidism
      remains unclear. METHOD: Of 239 consecutive patients who underwent targeted
      parathyroidectomy with intraoperative parathormone monitoring, 96 were followed
      for >= 10 years. NPE was defined as a normal serum calcium level and parathormone
      (PTH) above the normal reference range >= 6 months after successful
      parathyroidectomy. Recurrence was defined as elevated serum calcium and PTH
      levels >= 6 months after parathyroidectomy. Risk factors for NPE, patterns of
      postoperative PTH variation, and 10-year outcomes were analyzed. RESULTS: Of 96
      patients followed >= 10 years, 42 had postoperative NPE. Only male gender (P =
      .008) was a risk factor for NPE, and NPE did not predict recurrence. Three
      patterns of postoperative NPE were identified in patients with >= 3 PTH
      measurements over this 10-year period. Group 1 (n = 11): 1 to 2 consecutive PTH
      elevations; none recurred, and most were explained by physiologic variation.
      Group 2 (n = 23): multiple PTH fluctuations; 3 recurred, and almost all had
      physiologic variations. Group 3 (n = 4): PTH always elevated; 2 recurred.
      CONCLUSION: Postoperative NPE may be a dynamic, reversible, and transient
      clinical entity that does not predict recurrence. Nevertheless, patients with
      postoperative NPE should be monitored and an attempt made to correct any obvious
      potential causes of PTH elevation.

PMID- 22136825
TI  - Risk stratification of indeterminate thyroid fine-needle aspiration biopsy
      specimens based on mutation analysis.
AB  - BACKGROUND: Mutation analysis is potentially a powerful tool to enhance the
      diagnostic accuracy of thyroid fine-needle aspiration (FNA) biopsy specimens.
      However, some clinicians may rely on a negative mutation panel to exclude
      malignancy. We aimed to determine the malignancy rate in indeterminate lesions
      with negative mutation analysis. METHODS: A literature review established a
      mutation analysis model using the prevalence of BRAF, RET, RAS, and
      PAX8/peroxisome proliferator-activated receptor-gamma mutations in indeterminate
      lesions. This model was applied retrospectively to a study cohort of 466
      consecutive indeterminate lesions that underwent hemi- or total thyroidectomy for
      definitive diagnosis, to evaluate its accuracy for identifying malignancy.
      RESULTS: Of 466 indeterminate lesions in the study, 30% (139) were malignant.
      These included 66 cases of papillary thyroid cancer, 45 cases of follicular
      variant of papillary thyroid cancer, 18 cases of follicular thyroid cancer, and
      10 others. The risk of malignancy was 42% when cytologic atypia was present vs
      17% without. The mutation analysis model would correctly identify only 48 of 139
      (34%) of malignant indeterminate lesions. Therefore, when mutation analysis is
      negative, the overall risk of malignancy would be 23%. When atypia is present,
      the risk of malignancy would be 31% vs 13% in lesions without. CONCLUSION:
      Indeterminate lesions with a negative mutation analysis still carry a significant
      risk of malignancy, especially in the presence of atypia, requiring surgery for
      definitive diagnosis.

PMID- 22136826
TI  - Good question.

PMID- 22136827
TI  - Elevated parathyroid hormone predicts mortality in dialysis patients undergoing
      valve surgery.
AB  - BACKGROUND: Dialysis patients requiring valve surgery have high morbidity and
      mortality rates. Although elevated serum parathyroid hormone (PTH) levels are
      associated with increased mortality in dialysis patients, this correlation has
      not been investigated in patients undergoing cardiac valve operations. This study
      assesses the impact of PTH levels on mortality in dialysis patients undergoing
      valve operations. METHODS: A retrospective analysis of 109 dialysis patients
      undergoing valve operation with preoperative PTH levels between 1996 and 2007 at
      a US academic center was performed. Cox regression analyses were done using PTH
      as a binary variable. The patients were followed from the date of the operative
      procedure until death or loss to follow-up. RESULTS: Higher mortality risk was
      seen once preoperative PTH exceeded 200 pg/mL (hazard ratio [HR], 3.43; P =
      .003). Mean survival was improved in the PTH < 200 pg/mL group when compared with
      the PTH >= 200 pg/mL group (86.7 vs 40.3 months, respectively). Other independent
      predictors of mortality included serum phosphate (HR, 1.20; P = .017), calcium
      phosphate product (HR, 1.02; P = .038), and history of myocardial infarction (HR,
      2.12; P = .015). CONCLUSION: Preoperative PTH level >= 200 pg/mL is predictive of
      increased mortality after valve surgery among dialysis patients.
      Hyperparathyroidism should be investigated further as a possible modifiable risk
      factor for postoperative mortality in this high-risk patient cohort.

PMID- 22136828
TI  - The phenotype of primary hyperparathyroidism with normal parathyroid hormone
      levels: how low can parathyroid hormone go?
AB  - BACKGROUND: While normocalcemic hyperparathyroidism is well recognized in primary
      hyperparathyroidism (PHP), less is known about patients with high calcium but
      normal intact parathyroid hormone (iPTH). We aimed to describe this entity and
      designated it normohormonal primary hyperparathyroidism (NHPHP). METHODS: From a
      prospectively maintained database of patients undergoing bilateral parathyroid
      exploration for PHP, we identified and compared those with preoperative iPTH
      levels below (NHPHP) and above (typical PHP) normal reference peak (60 pg/mL).
      RESULTS: NHPHP occurred in 46 of 843 patients (5.5%) undergoing initial
      parathyroidectomy for PHP. All had hypercalcemia (11.1 mg/dL). Regarding
      preoperative iPTH, 7 patients (15%) had values <40 pg/mL, 19 (41%) had values <60
      pg/mL; and 20 (44%) had intermittent values >60 pg/mL. Unlike patients with
      elevated iPTH, nearly all NHPHP patients had additional testing delaying the
      operation. Imaging correctly localized NHPHP parathyroid disease in 80%. At the
      time of operation, 74% of NHPHP patients had single adenomas. Intraoperatively
      postmobilization, using the same assay that was used preoperatively, 82% had PTH
      levels >60 pg/mL (mean, 279 pg/mL). During the follow-up period, iPTH levels
      remained lower among NHPHP patients (21 pg/mL) compared to 41 pg/mL for patients
      with preoperative iPTH 60 to 100 pg/mL and 56 pg/mL for patients with
      preoperative iPTH 100 to 200 pg/mL (P < .0001). CONCLUSION: Lower PTH set points
      may exist in some patients with otherwise typical PHP features. Although high
      normal iPTH is inappropriate for hypercalcemia and should suggest PHP, this
      disorder may occur with iPTH levels as low as 5 pg/mL. Awareness of the unusual
      phenotype of NHPHP may facilitate earlier diagnosis and surgery.

PMID- 22136829
TI  - Population-level predictors of persistent hyperparathyroidism.
AB  - BACKGROUND: Systematic study of outcomes of initial surgery for primary
      hyperparathyroidism (PHPT) has been limited by selection and self-reporting
      biases. To avoid these biases, we evaluated parathyroidectomy (PTx) outcomes
      within an integrated health care system encompassing 3.25 million enrollees.
      METHODS: All patients undergoing PTx for PHPT from 1995 to 2010 were studied.
      Persistent and recurrent disease were defined by a serum calcium level >10.5
      mg/dL before or after 6 months postoperatively, respectively. The effect of
      demographic, clinical, and hospital volume-related variables was assessed by the
      use of multivariate logistic regression. RESULTS: A total of 1,190 initial
      operations for PHPT were performed at 14 hospitals. Follow-up calcium levels were
      available in 97% of subjects. The overall success rate was 92%, and 5% of
      patients developed recurrent disease. Age >= 70 years was predictive of
      persistent disease (odds ratio 1.80, P < .05). High-volume hospital (>100 cases)
      predicted against persistent disease (odds ratio 0.42, P < .05) and carried 96%
      success rate. Negative or equivocal sestamibi scan was associated with a lower
      success rate (success rate 89% vs 95% for positive scan, P < .05). Reoperation
      was performed in 12% of patients with persistent or recurrent PHPT. CONCLUSION:
      The success rate of PTx is influenced by patient age, hospital volume, and
      sestamibi scan result. Surgical outcomes may be optimized by designating high
      volume centers in the community setting.

PMID- 22136830
TI  - Population-level predictors of persistent hyperparathyroidism.

PMID- 22136831
TI  - Comparison of 6-18F-fluoro-L-DOPA, 18F-2-deoxy-D-glucose, CT, and MRI in patients
      with pancreatic neuroendocrine neoplasms with von Hippel-Lindau disease.
AB  - INTRODUCTION: There are limited data on the utility of 6-(18)F-fluoro-l-3,4
      dihydroxyphenylalanine ((18)F-DOPA) and (18)F-2-deoxy-d-glucose ((18)F-FDG) in
      the workup of patients with pancreatic neuroendocrine tumors (PNETs). The aim of
      our study was to determine the accuracy of (18)F-DOPA and (18)F-FDG to detect
      PNETs in patients with von Hippel-Lindau disease (vHL). METHODS: We studied
      prospectively 69 patients with a diagnosis of vHL and pancreatic lesion(s) using
      computed tomography (CT), magnetic resonance imaging (MRI), (18)F-FDG, and (18)F
      DOPA. Clinical, genetic, and laboratory characteristics were analyzed to
      determine association with imaging study results. RESULTS: In sum, 40 patients
      underwent evaluation by all 4 modalities; 98 PNETs and 55 PNETs were identified
      on CT and MRI, respectively. Only 11 of the 98 lesions (11%) were positive on
      (18)F-DOPA and 45 of the 98 (46%) lesions were positive on (18)F-FDG. There were
      13 (18)F-DOPA and 26 (18)F-FDG avid extrapancreatic lesions. One patient
      underwent resection of an (18)F-DOPA avid extrapancreatic lesion in the lung,
      with pathology demonstrating a NET. There was no association between (18)F-DOPA
      and (18)F-FDG avidity and tumor size, age, gender, vHL mutation, or serum
      chromogranin A level. CONCLUSION: (18)F-FDG and MRI may be adjuncts to CT in
      identifying PNETs and metastatic disease. (18)F-DOPA has limited value in
      identifying PNETs in patients with vHL, but may be useful for identifying
      extrapancreatic NET lesions.

PMID- 22136832
TI  - Zollinger-Ellison syndrome associated with a history of alcohol abuse:
      coincidence or consequence?
AB  - BACKGROUND: This 47-year observational study suggests that sporadic Zollinger
      Ellison (Z-E) syndrome, particularly duodenal wall gastrinomas (DWG), is
      associated with a history of alcohol abuse. METHODS: Thirty-nine consecutive Z-E
      patients were followed from 1962 through 2010. The drinking patterns of these
      patients were assessed and compared with 3,786 community controls. RESULTS:
      Thirty-five patients had extrapancreatic gastrinomas (34 DWG and/or paraduodenal
      lymph nodes, 1 antral gastrinoma). Total gastrectomy was done in 24; 9 underwent
      less extensive operations to remove DWG, and 2 patients had no operations. There
      were no deaths from tumor progression. Four patients presented with pancreatic
      gastrinoma (PG) and liver metastasis, all died from tumor progression. Alcohol
      abuse (>50 g/d) was documented in 81% of patients with DWG and/or paraduodenal
      lymph nodes. The drinking patterns (drinks per day) of DWG patients were
      significantly different: DWG vs community control-abstainers, 3% vs 24%; 1-2
      drinks, 16% vs 62%; 3-5 drinks, 29% vs 12%; and >= 6 drinks, 52% vs 2.5% (P <
      .01). CONCLUSION: Alcohol abuse is strongly associated with and may be a risk
      factor for sporadic Z-E with extrapancreatic DWG. Liver metastases and tumor
      deaths were not observed in this subgroup, supporting the concept that DWG and PG
      are different tumor entities.

PMID- 22136833
TI  - SSTR5 P335L monoclonal antibody differentiates pancreatic neuroendocrine
      neuroplasms with different SSTR5 genotypes.
AB  - BACKGROUND: Somatostatin receptor type 5 (SSTR5) P335L is a hypofunctional,
      single nucleotide polymorphism of SSTR5 with implications in the diagnostics and
      therapy of pancreatic neuroendocrine neoplasms. The purpose of this study is to
      determine whether a SSTR5 P335L-specific monoclonal antibody could sufficiently
      differentiate pancreatic neuroendocrine neoplasms (PNENs) with different SSTR5
      genotypes. METHODS: Cellular proliferation rate, SSTR5 mRNA level, and SSTR5
      protein level were measured by performing MTS assay, a quantitative reverse
      transcription polymerase chain reaction study, Western blot analysis, and
      immunohistochemistry, respectively. SSTR5 genotype was determined with the TaqMan
      SNP Genotyping assay (Applied Biosystems, Foster City, CA). RESULTS: We found
      that the SSTR5 analogue RPL-1980 inhibited cellular proliferation of CAPAN-1
      cells more than that of PANC-1 cells. Only PANC-1 (TT) cells, but not CAPAN-1
      (CC) cells expressed SSTR5 P335L. In 29 white patients with PNENs, 38% had a TT
      genotype for SSTR5 P335L, 24% had a CC genotype for WT SSTR5, and 38% hada CT
      genotype for both SSTR5 P335L and WT SSTR5. Immunohistochemistry using SSTR5
      P335L monoclonal antibody detected immunostaining signals only from the
      neuroendocrine specimens with TT and CT genotypes, but not those with CC
      genotypes. CONCLUSION: A SSTR5 P335L monoclonal antibody that specifically
      recognizes SSTR5 P335L but not WT SSTR5 could differentiate PNENs with different
      SSTR5 genotypes, thereby providing a potential tool for the clinical diagnosis of
      PNEN.

PMID- 22136834
TI  - Achieving eugastrinemia in MEN1 patients: both duodenal inspection and formal
      lymph node dissection are important.
AB  - BACKGROUND: Controversy exists regarding the role and extent of operation for
      patients with multiple endocrine neoplasia type 1 (MEN1) and hypergastrinemia.
      METHODS: An institutional MEN1 database was reviewed to identify patients with
      evidence of hypergastrinemia. The relationship of extent of resection to
      achievement of eugastrinemia was evaluated. RESULTS: Operation was performed in
      20 patients with MEN1 and hypergastrinemia with a median follow-up of 71 months.
      Duodenal gastrinomas were identified in 85% of patients who underwent duodenal
      evaluation. Nodal metastases were identified in 80%. Patients who underwent
      anatomic regional lymph node dissection (RLND) had a median of 16 nodes removed,
      vs 1 in patients who did not undergo a formal regional lymphadenectomy.
      Eugastrinemia was achieved in 12 patients (60%), and 8 (40%) had persistent
      hypergastrinemia. Compared with patients with persistent hypergastrinemia,
      patients rendered eugastrinemic more often underwent duodenal evaluation (11/12
      vs 2/8; P = .01) and RLND (11/12 vs 3/8; P = .03); there was no relationship
      between pancreatic resection and achievement of eugastrinemia (P = .32).
      CONCLUSION: For patients with MEN1-associated hypergastrinemia selected for
      operative treatment, a strategy including duodenal evaluation and anatomic
      regional lymphadenectomy is associated with long-term eugastrinemia. In contrast,
      the extent of pancreatic resection should be dictated by the extent and
      distribution of pancreatic neuroendocrine neoplasms, rather than by the presence
      of hypergastrinemia.

PMID- 22136835
TI  - Case series of targeted parathyroidectomy with surgeon-performed ultrasonography
      as the only preoperative imaging study.
AB  - BACKGROUND: Targeted parathyroidectomy for treatment of sporadic primary
      hyperparathyroidism (SPHPT) has become the preferred approach in many centers.
      Therefore, preoperative localization studies are increasingly important. Although
      surgeon-performed ultrasonography (SUS) is equivalent to sestamibi scanning
      (MIBI), many surgeons still obtain either a MIBI or both studies before cervical
      exploration. The goal of this study was to demonstrate the feasibility of
      targeted parathyroidectomy guided by intraoperative PTH monitoring (IPM) based on
      SUS localization alone. METHODS: We studied 136 consecutive patients with SPHPT
      undergoing parathyroidectomy guided by IPM. Ninety-six (71%) patients had only
      SUS, whereas 40 (29%) also had a negative MIBI (total n = 136). Pre-, intra- and
      postoperative data were analyzed to evaluate SUS accuracy in localizing abnormal
      glands. RESULTS: SUS correctly identified >= 1 abnormal gland in 90% (123/136) of
      the patients. Sensitivity and overall accuracy of SUS was 87% and 88%,
      respectively. Operative success was 99% with multiglandular disease incidence of
      10%. Unilateral neck exploration was possible in the majority of patients.
      CONCLUSION: Preoperative SUS is accurate in localizing hypersecreting glands;
      however, IPM remains paramount in determining the extent of neck dissection. The
      use of SUS as a single imaging method obviates the need for MIBI in most patients
      and decreases costs of parathyroidectomy guided by IPM.

PMID- 22136836
TI  - The incidence of central neck micrometastatic disease in patients with papillary
      thyroid cancer staged preoperatively and intraoperatively as N0.
AB  - BACKGROUND: In papillary thyroid cancer, the incidence of regional lymph node
      metastasis in the central compartment has been reported to be between 21% and
      60%. This study sought to establish the rate of micrometastatic disease in the
      central neck in patients staged as N0 by preoperative and intraoperative
      assessment. METHODS: We studied 72 consecutive patients with diagnoses of
      papillary thyroid cancer without preoperative or intraoperative evidence of
      central neck metastases. They underwent total thyroidectomies and were given
      elective central compartment neck dissection (CCND) ispsilateral to the lobe
      harboring the tumor or bilaterally in cases of primary tumor located in the
      isthmus. RESULTS: Of the patients, 30 underwent right CCND, 30 underwent left
      CCND, and in 12 cases the dissection was bilateral. The incidence of lymph node
      micrometastasis was 25%. Male gender and histologic type showed association with
      lymph node micrometasis. Among these cases, 7% had temporary vocal cord palsy,
      and 8% had temporary hypoparathyroidism. No cases of definitive vocal cord palsy
      or definitive hypocalcemia were observed. After the procedure 8 patients were up
      staged according to the American Joint Committee on Cancer staging system.
      CONCLUSION: Despite being a safe procedure, this relatively low rate of
      micrometastatic disease emphasizes the need for a careful weighing of the risks
      and benefits of elective CCND.

PMID- 22136837
TI  - Preoperative basal calcitonin and tumor stage correlate with postoperative
      calcitonin normalization in patients undergoing initial surgical management of
      medullary thyroid carcinoma.
AB  - BACKGROUND: The optimal initial operative management of medullary thyroid cancer
      (MTC) and the use of biomarkers to guide the extent of operation remain
      controversial. We hypothesized that preoperative serum levels of calcitonin and
      carcinoembryonic antigen (CEA) correlate with extent of disease and postoperative
      levels reflect the extent of operation performed. METHODS: We assessed
      retrospectively clinical and pathologic factors among patients with MTC
      undergoing at least total thyroidectomy; these factors were correlated with
      biomarkers using regression analyses. RESULTS: Data were obtained from 104
      patients, 28% with hereditary MTC. Preoperative calcitonin correlated with tumor
      size (P < .001) and postoperative serum calcitonin levels (P = .01) after
      multivariable adjustment for lymph node positivity, extent of operation, and
      hereditary MTC. No patient with a preoperative calcitonin level of <53 pg/mL (n =
      20) had lymph node metastases. TNM stage (P = .001) and preoperative calcitonin
      levels (P = .04), but not extent of operation, independently correlated with the
      failure to normalize postoperative calcitonin. Postoperative CEA correlated with
      positive margins (adjusted P = 04). Neither preoperative nor postoperative CEA
      was correlated with lymph node positivity or extent of surgery. CONCLUSION:
      Preoperative serum calcitonin and TMN stage, but not extent of operation, were
      independent predictors of postoperative normalization of serum calcitonin levels.
      Future studies should evaluate preoperative serum calcitonin levels as a
      determinate of the extent of initial operation.

PMID- 22136838
TI  - A quantitative tool to assess degree of sarcopenia objectively in patients with
      hypercortisolism.
AB  - BACKGROUND: Muscle weakness and wasting are known manifestations of
      hypercortisolism (HC). Central sarcopenia is a marker of frailty and predicts
      mortality. The hypothesis of this study is that central sarcopenia can be used as
      a marker of disease severity and frailty in patients with HC. METHODS: Psoas
      muscle area and psoas muscle density (PMD) were measured at specific points on CT
      scans of patients with HC using a defined protocol. We compared 24-hour urine
      cortisol (24HUC) levels by time point to each CT scan. A linear regression model
      was used to describe the relationship between 24HUC and morphometric variables. A
      comparison with matched non-HC patients was performed. RESULTS: We identified 45
      patients (34 female). The median age was 46 years (range, 14-80); the median
      24HUC was 211 mg/dL (range, 9.5-39,500); the median PMD was 50.1 24HUC (range, 20
      72). An inverse correlation (-0.29) between 24HUC levels and PMD was noted (P =
      .045). Intra-abdominal fat was also significantly and positively correlated with
      24HUC: 27 non-HC patients matched for age, sex, and body-mass index showed higher
      (58 vs 51) PMD (P = .0127) compared to those with HC. CONCLUSION: PMD and intra
      abdominal fat are significantly related to 24HUC levels. Morphometric measures of
      the overall burden of HC may allow more precise assessment of disease severity.

PMID- 22136839
TI  - Comparison of clinical and imaging features in succinate dehydrogenase-positive
      versus sporadic paragangliomas.
AB  - BACKGROUND: Limited data exist concerning the clinical and imaging features that
      distinguish sporadic from familial paragangliomas (PGLs). METHODS: Clinical,
      genetic (succinate dehydrogenase [SDHB] vs no SDHx), and imaging (computed
      tomography [CT], magnetic resonance imaging, (18)F-fluoro-deoxy-glucose positron
      emission tomography [(18)F-FDG-PET]) features obtained during a decade in 124 PGL
      patients were studied. Data were analyzed by Fisher's exact test or Wilcoxon rank
      sum test. RESULTS: Mean age at diagnosis was younger in the SDHB-positive (SDHB+)
      group compared with the sporadic (no SDHx) group (28 vs 39 years, respectively, P
      < .001). Rate of supradiaphragmatic neoplasms were greater in the SDHB+ group
      (16.7 vs 4.7%, P = .11). Metastasis rates were greater in the SDHB+ group (78.9
      vs 48.3%, P < .001), as was the existence of metastases or multiple PGLs at
      presentation (38.5 vs 16.7%, P < .05). Tumor volumes >250 mL were exclusively
      observed in SDHB+ patients (P < .05). On CT, SDHB+ tumors were more enhanced (P <
      .05). On (18)F-FDG-PET, SDHB+ tumors' had greater mean standard uptake values
      (12.3 vs 8.0, P < .05). CONCLUSION: Clinically young age, large tumor volume,
      greater rate of metastatic and multifocal PGLs, greater SUV values on (18)F-FDG
      PET, and increased CT enhancement are observed in SDHB+ PGLs. These findings may
      warrant genetic screening. Because SDHB+ patients demonstrate more
      supradiaphragmatic lesions, whole-body imaging may be of particular value in
      these patients.

PMID- 22136840
TI  - Is genetic screening indicated in apparently sporadic pheochromocytomas and
      paragangliomas?
AB  - BACKGROUND: Pheochromocytoma (Pheo) is usually considered a sporadic disease.
      Recently, an increasing rate of genetically based tumors has been reported.
      However, the need for systematic screening of unsuspected germline mutations in
      apparently sporadic forms is still debated. This study aimed to assess the
      effective rate of germline mutations causing Pheo and Paraganglioma (PGL), and
      the role of systematic genetic screening. METHODS: Demographics, clinical, and
      genetic evaluation were performed in a series of 71 patients with Pheo and/or
      PGL. RESULTS: Twelve patients had evident inherited/familial disease at
      presentation: NF1 (n = 4); MEN2 (n = 4), and familial Pheo/PGL (n = 4). Among 59
      patients with apparently sporadic disease, unsuspected germline mutations
      occurred in 8 cases: TMEM127 (n = 4), SDHB (n = 2), VHL (n = 1), SDHC (n = 1). No
      differences were found between hereditary and sporadic disease concerning age,
      sex, and tumor size; bilateral Pheo and/or PGL and recurrences occurred most
      often in hereditary disease. CONCLUSION: Hereditary Pheo and/or PGL are frequent
      (28.2%). Inheritance is evident at presentation only in 16.9% of cases; 13.6% of
      apparently sporadic variants are genetically determined. Despite increased costs,
      systematic genetic screening might be useful because it might lead to a stricter
      follow-up, early diagnosis of recurrences in index cases and presymptomatic
      detection of disease in relatives.

PMID- 22136841
TI  - Cardiovascular dysfunction and catecholamine cardiomyopathy in pheochromocytoma
      patients and their reversal following surgical cure: results of a prospective
      case-control study.
AB  - BACKGROUND: Cardiovascular (CV) dysfunction and cardiomyopathy can cause
      perioperative morbidity in pheochromocytoma patients, but have not been studied
      systematically. This prospective, case-control study evaluated nature and extent
      of CV dysfunctions and their reversal following curative pheochromocytoma
      surgery. METHODS: Thirty-five pheochromocytoma patients, 9 normotensive
      nonpheochromocytoma adrenal tumors and 10 essential hypertensives were evaluated
      with 2-dimensional echocardiography, tissue Doppler, and serum N-terminal pro
      brain natriuretic peptide (s-NTpro-BNP, a sensitive myocardial damage biomarker)
      serially before and after treatment. RESULTS: Pheochromocytoma patients had
      systolic and diastolic dysfunction, reduced left ventricular (LV) ejection
      fraction (EF), increased LV end-diastolic and systolic dimensions and volumes,
      myocardial performance index, and decreased transmitral early/late velocity
      ratio, which were worse compared with controls. All indices improved
      significantly with alpha-blockade and after pheochromocytoma resection, and
      normalized over 3-6 months. Tissue Doppler early velocity was lower (P = .04) and
      s-NT-proBNP higher (P = .0001) in pheochromocytoma patients compared with
      controls. Seven pheochromocytoma patients (20%) had significant LV dysfunction
      (LVEF <45%; s-NTpro-BNP levels >500 pg/mL) and had more marked postoperative
      improvement. CONCLUSION: Global LV diastolic and systolic dysfunctions specific
      to pheochromocytoma are common and improve early postoperatively, with sustained
      improvement upon follow-up. Detailed cardiac evaluation with echocardiography,
      tissue Doppler, and s-NTpro-BNP may help to reduce perioperative morbidity and
      monitor recovery in pheochromocytoma patients.

PMID- 22136842
TI  - Prospective application of our novel prognostic index in the treatment of
      anaplastic thyroid carcinoma.
AB  - BACKGROUND: We have previously performed retrospective analysis of patients with
      anaplastic thyroid carcinoma (ATC) treated between April 1976 and March 1999,
      revealing acute symptoms, large tumor (>5 cm), distant metastasis, and
      leukocytosis >= 10,000/mm(3) as the most important prognostic factors. We devised
      a novel prognostic index (PI) as the total number of these 4 factors present,
      giving a PI of 0-4. METHODS: We have adopted this PI since April 1999. In
      principle, multimodal treatment has been encouraged for a PI of <= 1, whereas
      aggressive treatment has been avoided to maintain quality of life for a PI of >=
      3. The validity of this therapeutic strategy was prospectively investigated in 74
      patients with ATC. RESULTS: Six-month survival rates for PI <= 1 and PI >= 3 were
      72% and 12%, respectively. Among patients with a PI of <= 1,11 (42%) underwent
      multimodal treatment and showed significantly better survival than previous
      cases. Survival rates did not differ between stages. For patients with a PI of >=
      3, survival rates were equally dismal, regardless of stage. Numbers of patients
      who underwent tracheostomy or died from local disease were significantly
      decreased compared with previous cases. CONCLUSION: Our PI is valid for
      anticipating prognosis and aiding timely decisions on treatment policy for ATC
      patients.

PMID- 22136843
TI  - Anaplastic thyroid carcinoma: hope on the horizon?

PMID- 22136844
TI  - Motor and sensory branching of the recurrent laryngeal nerve in thyroid surgery.
AB  - INTRODUCTION: Recognition of extralaryngeal bifurcation of the recurrent
      laryngeal nerve (RLN) is crucial, because inadvertent intraoperative division may
      lead to significant morbidity. The purpose of this study was to examine the
      incidence of extralaryngeal bifurcation of the RLN and the distance that the
      initial bifurcation occurs from the cricothyroid insertion site of the RLN. We
      also sought to demonstrate the location of the RLN branches containing a
      predominance of motor fibers. METHODS: This prospective study of 220 patients
      with data on 310 RLNs collected the type of operation, incidence of bifurcation,
      distance from the cricothyroid insertion point to the point of initial
      bifurcation, and location of the motor fibers by assessing a stimulus response on
      the Medtronic NIMS as they relate to the laryngeal muscles. RESULTS: A total of
      310 RLNs in 220 patients were studied. There were 133 RLNs (42.9%) that
      bifurcated before entering the larynx. These bifurcations occurred 51.1% on the
      right, 48.9% on the left, and 33.3% bilaterally. The median branching distance
      from the cricothyroid membrane on the right was 6.33 mm, and on the left was 6.37
      mm. In all bifurcated RLNs, the motor fibers were located exclusively in the
      anterior branches. CONCLUSION: Extralaryngeal bifurcation was found in 42.9% of
      the RLNs in this case series. The motor fibers are located in the anterior
      branches. Great caution is therefore required after the presumed identification
      of the RLN to ensure there is no unidentified anterior branch.

PMID- 22136845
TI  - Predictive factors of malignancy in pediatric thyroid nodules.
AB  - BACKGROUND: Studies suggest that while most pediatric thyroid nodules are benign,
      there is a higher rate of malignancy than in adults. We investigate clinical
      factors that may predict malignancy in pediatric thyroid nodules. METHODS: A
      retrospective review of 207 pediatric thyroidectomies was conducted over 15 years
      at 2 tertiary hospitals. Analyses examined predictive values of 16
      clinicopathologic factors associated with cancer. Positive predictive values
      (PPVs) of fine-needle aspiration biopsy specimens (FNABs) were analyzed
      independently. RESULTS: Malignancy occurred in 41% of patients. After excluding
      missing data, malignancy was more likely with family history of thyroid cancer
      (34.2% vs 17.7%; P = .111), palpable lymphadenopathy (34.2% vs 2.9%; P = .001),
      and hypoechoic nodules (52.2% vs 19.2%; P = .016). Palpable lymphadenopathy
      indicated greater than 2-fold increased risk for malignancy (relative risk, 2.18;
      95% confidence interval, 1.56-3.05). PPVs of FNAB results were 0.94 for
      malignancy, 0.63 for suspicious for malignancy, and 0.55 for indeterminate
      lesions. PPV for benign FNAB to be benign on final pathology was 0.71.
      CONCLUSION: While malignancy is associated with family history of thyroid cancer
      and hypoechoic lesions, palpable lymphadenopathy had the greatest risk. When
      compared to adults, a benign FNAB in children is not as accurate and the
      likelihood that an indeterminate nodule is cancer is greater.

PMID- 22136846
TI  - The impact of atypia/follicular lesion of undetermined significance on the rate
      of malignancy in thyroid fine-needle aspiration: evaluation of the Bethesda
      System for Reporting Thyroid Cytopathology.
AB  - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was
      developed to refine definitions and improve clinical communication and
      management. This study evaluates the impact of the BSRTC in a large cohort of
      patients undergoing thyroidectomy before and after its adoption at a single
      institution. METHODS: The records from 469 patients in the pre-BSRTC (n = 187)
      and post-BSRTC (n = 282) periods were reviewed. Cytologic categories in group 1
      included nondiagnostic, benign, follicular/Hurthle neoplasm, suspicious for
      malignancy, and malignant. Atypia/follicular lesion of undetermined significance
      (AUS/FLUS) was included in group 2. The percentage of each fine-needle aspiration
      (FNA) category, malignancy rate per category, and rate of AUS/FLUS utilization
      were calculated. RESULTS: Group 1 FNA results included 3% (n = 6) nondiagnostic,
      48% (n = 89) benign, 17% (n = 32) follicular/Hurthle, 13% (n = 25) suspicious for
      malignancy, and 19% (n = 35) malignant. Group 2 results included 4% (n = 11)
      nondiagnostic, 34% (n = 96) benign, 29% (n = 82) AUS/FLUS, 12% (n = 33)
      follicular/Hurthle, 10% (n = 29) suspicious for malignancy, and 11% (n = 31)
      malignant. The rate of cancer changed from 25% to 36% for follicular/Hurthle
      lesions. AUS/FLUS was utilized in 154 of 1095(14%) FNAs reviewed with a
      malignancy rate of 20%. CONCLUSION: The new AUS/FLUS category was used more often
      than recommended (14%) with a higher than expected rate of malignancy (20%).
      Rigorous cytopathology to histopathology correlation is needed to accurately
      reflect the malignancy rates of the different BSRTC categories at each individual
      institution. Clinical management should be tailored based on such institutional
      findings.

PMID- 22136847
TI  - The impact of microscopic extrathyroid extension on outcome in patients with
      clinical T1 and T2 well-differentiated thyroid cancer.
AB  - OBJECTIVE: To report the impact of microscopic extrathyroid extension (ETE) on
      outcome in patients with cT1/cT2 well-differentiated thyroid cancer (WDTC), and
      to determine the effect of extent of surgery and adjuvant radioactive iodine
      (RAI) treatment on outcome in patients with microscopic ETE. PATIENTS AND
      METHODS: From an institutional database, we identified 984 patients (54%) who
      underwent surgery for cT1/T2N0 disease. Of these, 869 patients were pT1/T2 and
      115 were upstaged to pT3 based on the finding of microscopic ETE. Disease
      specific survival (DSS) and recurrence-free survival (RFS) were analyzed for each
      group using the Kaplan-Meier method. In the pT3 group, factors predictive of
      outcome were analyzed by univariate and multivariate analyses. RESULTS: There was
      no difference in the 10-year DSS (99% vs 100%; P = .733) or RFS (98% vs 95%; P =
      .188) on comparison of the pT1/pT2 and pT3 cohorts. Extent of surgery and
      administration of postoperative RAI were not significant for recurrence on
      univariate or multivariate analysis in the pT3 cohort. CONCLUSION: Outcomes in
      patients with cT1T2N0 WDTC are excellent and not affected by microscopic ETE. The
      extent of resection and administration of postoperative RAI in patients with
      microscopic ETE does not impact survival or recurrence.

PMID- 22136848
TI  - Effect of postoperative thyrotropin suppressive therapy on bone mineral density
      in patients with papillary thyroid carcinoma: a prospective controlled study.
AB  - BACKGROUND: The influence of thyrotropin (thyroid-stimulating hormone [TSH])
      suppressive therapy on bone mineral density (BMD) remains contentious. We have
      conducted a randomized controlled trial evaluating the effects of postoperative
      TSH suppressive therapy on disease-free survival for papillary thyroid carcinoma
      (PTC) since 1996, while prospectively verifying the effects of TSH suppression on
      BMD. METHODS: Lumbar spine BMD as expressed by T-score was examined annually in
      female patients randomly assigned to receive TSH suppressive therapy (group A; n
      = 144) or no therapy (group B; n = 127). RESULTS: The mean TSH level was 0.07 +/-
      0.10 mU/L in group A and 3.14 +/- 1.69 mU/L in group B. Group B did not show any
      significant decrease in T-score until 5 years postoperatively, whereas group A
      had a significant deterioration from 1 year postoperatively. Among group A
      patients, significant decreases in T-score within 1 year were seen in patients >=
      50 years of age, but not in those <50 years of age. After 5 years of TSH
      suppression, 20 patients had T-scores below -2.0 and 100 patients did not. These
      former patients were significantly older and had lower preoperative BMD
      measurements than the latter. CONCLUSION: This prospective controlled trial
      suggests that TSH suppression after surgery for PTC has adverse effects on BMD in
      women >= 50 years of age.

PMID- 22136849
TI  - Activation of mTOR signaling in medullary and aggressive papillary thyroid
      carcinomas.
AB  - BACKGROUND: Because mammalian target of rapamycin (mTOR) may be involved in
      thyroid carcinogenesis, we investigated the expression and activation patterns of
      mTOR signaling proteins in thyroid carcinoma cells and tumors and their
      association with tumor histology and aggressiveness. METHODS: Tissue specimens
      from 50 patients with thyroid cancer were analyzed for eIF4E, a critical
      downstream target of the mTOR pathway, using immunohistochemistry. In addition,
      fresh-frozen samples from patients, and primary tumor cell cultures were analyzed
      for expression and activation of mTOR signaling proteins by Western blot.
      Moreover, pharmacologic studies with rapamycin were performed. RESULTS: High
      expression of eIF4E was observed in medullary thyroid carcinomas (MTC) and in
      aggressive variants of papillary thyroid carcinomas (PTC) as compared with
      conventional PTC and follicular thyroid carcinomas (P < .0001). The level of
      eIF4E expression also correlated with tumor stage (P = .002). Using Western blot
      analysis, p-rpS6, p-4EBP1, 4EBP1, and eIF4E were detected at higher levels in
      aggressive PTC and MTC cells. Treatment of MTC cells with increasing
      concentrations of rapamycin resulted in significant cell death and in decreased
      cell growth associated with deactivation of the mTOR pathway. CONCLUSION: mTOR
      signaling, which controls protein synthesis through regulation of translation
      initiation, is activated in aggressive PTC and MTC and represents a promising
      target for investigational therapies in these patients.

PMID- 22136850
TI  - Surgical completeness of bilateral axillo-breast approach robotic thyroidectomy:
      comparison with conventional open thyroidectomy after propensity score matching.
AB  - BACKGROUND: Bilateral axillo-breast approach (BABA) robotic thyroidectomy (RoT)
      has good postoperative and excellent cosmetic outcomes. To assess the surgical
      completeness of BABA RoT, it was compared to open thyroidectomy (OT) after
      propensity score matching of the cohorts. METHODS: Between 2008 and 2010, 760
      patients who underwent total thyroidectomy with central node dissection (CND)
      caused by papillary thyroid carcinoma (PTC) in Seoul National University Hospital
      were enrolled; 327 BABA robotic and 423 open method operations were performed. We
      selected 174 robotic and 237 open thyroidectomy patients who received radioactive
      iodine (RAI) ablation. Propensity score matching using 3 demographic and 5
      pathologic factors was used to generate 2 matched cohorts, each composed of 108
      patients. RESULTS: The matched BABA RoT and OT cohorts were not different with
      regard to the RAI uptake ratio, stimulated thyroglobulin (Tg) levels, or
      proportion of patients with stimulated Tg levels <1.0 ng/mL on the first
      ablation. The number of RAI ablation sessions and RAI doses needed to achieve a
      complete ablation also did not differ significantly. CONCLUSION: The surgical
      completeness of BABA RoT did not differ from OT. BABA RoT may be suitable for
      patients with PTC who prefer scarless neck surgery.

PMID- 22136851
TI  - Does the presence of thyroid cancer increase the risk of venous thromboembolism
      in patients undergoing thyroidectomy?
AB  - BACKGROUND: Venous thromboembolism (VTE) is a leading cause of postoperative
      morbidity and mortality in cancer patients. We evaluate the association between
      thyroid cancer (TCA) and VTE in thyroidectomy patients and assess the impact of
      TCA status on risk level using the American College of Surgeons National Surgical
      Quality Improvement Program (ACS NSQIP) Best Practices guideline. METHODS: A
      retrospective cohort study of thyroidectomy patients using the ACS NSQIP database
      (2005-2008) was performed. Patients were stratified by the presence (TCA) or
      absence (non-TCA) of TCA. The incidence of 30-day postoperative VTE and VTE risk
      factors were compared between groups. Risk factor scores (RFS) for VTE were
      computed with and without TCA as a factor. RESULTS: Fifteen VTE events were
      documented in 19,640 patients. The incidence of VTE was 0.08% in the TCA and
      0.07% in non-TCA groups (P = .783). TCA patients were younger, had a lower body
      mass index, and had longer operations than non-TCA patients. TCA patients had
      slightly higher RFS before inclusion of TCA (mean of 4.26 vs 4.16; P < .001).
      After adjustment for the RFS, TCA was not associated with an increased risk of
      VTE. CONCLUSION: TCA does not seem to be independently associated with VTE in
      patients undergoing thyroidectomy. The decision for anticoagulation should
      therefore be determined by individual patient risk factors.

PMID- 22136852
TI  - Would scan, but which scan? A cost-utility analysis to optimize preoperative
      imaging for primary hyperparathyroidism.
AB  - BACKGROUND: Minimally invasive parathyroidectomy for primary hyperparathyroidism
      depends on accurate preoperative localization. This study examines the cost
      utility of sestamibi in combination with single photon emission computed
      tomography (sestamibi-SPECT); ultrasound; and 4-dimensional computed tomography
      (4D-CT). METHODS: A decision tree was constructed for patients undergoing initial
      parathyroidectomy. Patients were randomized to 1 of 5 preoperative localization
      protocols: (1) ultrasound; (2) sestamibi-SPECT; (3) 4D-CT; (4) sestamibi-SPECT
      and ultrasound; and (5) sestamibi-SPECT and ultrasound and 4D-CT, if discordant
      (sestamibi-SPECT and ultrasound +/- 4D-CT). From a societal perspective, all
      relevant costs were included. Input data were obtained from literature and
      Medicare. The incremental cost-utility ratio was determined in dollars per
      quality-adjusted life years ($/QALY). Sensitivity analyses were performed.
      RESULTS: In the base-case, ultrasound was least expensive, with a cost of $6666,
      compared to $6773 (4-D CT); $7214 (sestamibi-SPECT and ultrasound +/- 4D-CT);
      $7330 (sestamibi-SPECT); and $7371(sestamibi-SPECT and ultrasound). Sestamibi
      SPECT and ultrasound +/- 4D-CT were most cost-effective because improved
      localization resulted in fewer bilateral explorations. QALY were comparable
      across modalities. Compared to sestamibi-SPECT, ultrasound, 4D- CT, and sestamibi
      SPECT and ultrasound +/- 4D-CT resulted a win-win situation-costing less and
      accruing more utility. Sensitivity analyses demonstrated that the model was
      sensitive to surgery cost and diagnostic accuracy of imaging. CONCLUSION: In our
      model, sestamibi-SPECT and ultrasound +/- 4D-CT were the most cost-effective
      methods, followed by 4D-CT and ultrasound. Sestamibi-SPECT alone was least cost
      effective. Cost-utilities were dependent on the sensitivities of ultrasound and
      4D-CT and may vary by institution.

PMID- 22136854
TI  - The founding of the American Association of Endocrine Surgeons: the time was
      right.

PMID- 22136853
TI  - Thyroid-specific knockout of the tumor suppressor mitogen-inducible gene 6
      activates epidermal growth factor receptor signaling pathways and suppresses
      nuclear factor-kappaB activity.
AB  - BACKGROUND: Mitogen-inducible gene 6 (Mig-6) is a putative tumor suppressor gene
      and prognostic biomarker in papillary thyroid cancer. We hypothesized that Mig-6
      knockout would activate pro-oncogenic signaling in mouse thyrocytes. METHODS: We
      performed a thyroid-specific knockout using the Cre/loxP recombinase system.
      RESULTS: Four knockout and 4 control mouse thyroids were harvested at 2 months of
      age. Immunoblotting confirmed Mig-6 ablation in knockout mice thyrocytes.
      Epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase
      (ERK) phosphorylation levels were increased in Mig-6 knockout compared to wild
      type mice. Total EGFR levels were similar in knockout and wild-type mice.
      However, EGFR was absent in the caveolae-containing membrane fraction of knockout
      mice, indicating that Mig-6 depletion is associated with a change in the membrane
      distribution of EGFR. Although p65 localized to the nucleus in wild-type mice, it
      was distributed in both cytoplasm and nucleus in knockouts, suggesting that Mig-6
      loss decreases p65 activity. CONCLUSION: Our results confirm the feasibility of
      targeted, thyroid-specific gene knockout as a strategy for studying the relevance
      of specific genes in thyroid oncogenesis. We suggest that the loss of Mig-6
      alters the membrane distribution of EGFR, which may limit receptor degradation
      and activate this oncogenic signaling pathway.

PMID- 22136855
TI  - Intranasal hypocretin-1: making sense of scents?

PMID- 22136856
TI  - Dabigatran for patients with a mechanical valve.

PMID- 22136857
TI  - The "Fringe Sign" - A useful clinical finding in traction alopecia of the
      marginal hair line.
AB  - INTRODUCTION: Traction alopecia is hair loss caused by prolonged or repetitive
      tension on the hair. Diagnostic challenges are encountered when the clinical
      suspicion is not high and when a history of traction is remote or not obtained.
      We have made the observation that the presence of retained hairs along the
      frontal and/or temporal rim, which we termed the "fringe sign," is a finding seen
      in both early and late traction alopecia, and may be a useful clinical marker of
      the condition. METHODS: This was a retrospective single-center review to
      determine the frequency of the fringe sign in patients with traction alopecia.
      RESULTS: Over a 3.5-year period the diagnosis of traction alopecia was made in 41
      women. Twelve of the 41 patients were Hispanic (29%). Thirty-five (85%) of all
      women and 100 percent of women who had traction involving the marginal hairline
      had the fringe sign. Fourteen biopsies (58%) were available for review.
      Histopathologic findings included retained sebaceous glands (100%), an increase
      in vellus-sized hairs (50%), a decrease in terminal hairs (100%), fibrotic
      fibrous tracts (100%), and sparse lymphocytic inflammation (57%). CONCLUSIONS:
      The fringe sign is a sensitive and specific clinical feature of traction alopecia
      when it involves the marginal hairline.

PMID- 22136858
TI  - Acute methotrexate toxicity seen as plaque psoriasis ulceration and necrosis: A
      diagnostic clue.
AB  - In addition to the well-known signs of methotrexate toxicity, rare cutaneous side
      effects have been described. These cutaneous signs may provide a diagnostic clue
      into the diagnosis of toxicity as well as facilitate early and aggressive
      therapy. We describe the case of a 37-year-old male, with a diagnosis of
      psoriasis, who developed characteristic signs and symptoms of acute methotrexate
      toxicity after receiving an unknown amount of intravenous methotrexate. The
      patient experienced a distinct change in the morphology of his existing psoriatic
      plaques, which became ulcerated and necrotic in the week following the
      methotrexate injection. Shortly after the development of cutaneous erosions, the
      patient developed pancytopenia, which ultimately led to his death. Ulceration and
      necrosis of cutaneous psoriasis plaques may serve as a herald for the impending
      development of life-threatening pancytopenia in patients with acute methotrexate
      toxicity.

PMID- 22136859
TI  - Waardenburg Syndrome type 1: A case report.
AB  - Waardenburg Syndrome (WS) is a rare hereditary disorder that is characterized by
      the clinical manifestations of oculocutaneous anomalies of pigmentation,
      congenital deafness, dystopia canthorum, and broad nasal root. It demonstrates
      both genetically and clinically heterogenous characteristics. In this article, we
      report an 11-month-old boy with WS1, one of four clinicat types of WS. He
      exhibited white forelock, hypopigmented macules and patches, heterochromia
      irides, and dystopia canthorum.

PMID- 22136860
TI  - An unusual adverse effect of nadroparin injections: Calcinosis cutis.
AB  - In 1988, Tumiati et al described the first case of calcinosis cutis related to a
      calcium-containing heparin. Since then, only 18 cases have been reported in the
      literature; they usually have an altered calcium-phosphate product, an elevated
      parathyroid hormone (PTH), or both. We report a 33-year-old patient who developed
      calcinosis cutis at sites of nadroparin injections without any disturbance of
      calcium-phosphate product, PTH, or vitamin D. The pathogenesis of calcinosis
      cutis secondary to nadroparin injections remains controversial; Proposed causes
      included metastatic, dystrophic, iatrogenic, or multifactorial etiologies. This
      is the first case of multiple nodules of calcinosis cutis without alterations of
      calcium-phosphate product, PTH, or vitamin D, which supports an iatrogenic
      mechanism. We also suggest that calcinosis cutis could be more frequent than we
      thought and is probably an underdiagnosed entity.

PMID- 22136861
TI  - Primary cutaneous actinomycosis caused by Actinomyces meyeri as first
      manifestation of HIV infection.
AB  - Primary cutaneous actinomycosis is very uncommon. We report a patient with
      cutaneous actinomycosis with multiple lesions without any detectable extra
      cutaneous lesions. In our patient the actinomycosis was the presenting
      manifestation of HIV infection.

PMID- 22136862
TI  - Sezary syndrome presenting with leonine facies and treated with low-dose
      subcutaneous alemtuzumab.
AB  - Cutaneous T-cell lymphomas (CTCL) comprise a group of diseases characterized by
      the accumulation of malignant T cells within the skin. Sezary syndrome represents
      an aggressive form of CTCL, in which the skin is diffusely affected and the
      peripheral blood is involved. It is characterized by the triad of generalized
      erythroderma, lymphadenopathy, and neoplastic T cells (Sezary cells) in the skin,
      lymph nodes, and peripheral blood. Leonine facies is rare and corresponds to the
      morphologic manifestation of diffuse dermal infiltration of the face. It can
      occur in cutaneous T-cell lymphomas that progress during years without therapy.
      We present the case of a 54-year-old man with Sezary syndrome presenting with
      leonine facies, unresponsive to conventional therapies; he exhibited a promising
      response to subcutaneous low-dose alemtuzumab.

PMID- 22136863
TI  - Acquired perforating dermatosis associated with metastatic colon cancer.
AB  - Acquired perforating dermatosis (APD) is a type of perforating disorder that is
      traditionally thought to be associated with diabetes, chronic renal failure, or
      occasionally liver disease. We report a case of APD in a patient with stage IV
      colon cancer with hepatic metastases. Although rare, APD associated with colon
      cancer is an important entity to consider; APD may be associated with a broader
      range of systemic diseases than previously recognized.

PMID- 22136864
TI  - [Lipoid proteinosis of Urbach-Wiethe: a case report].
AB  - Lipoid proteinosis or Urbach-Wiethe disease is a rare autosomal recessive
      mucocutaneous disorder caused by mutation in the EMC1 gene. Hoarseness is
      observed in early childhood associated with infiltration and thickening of skin.
      Multiple systemic manifestations develop involving mucosal deposition of hyalin
      material. We describe a 12-year-old boy with typical manifestations: a hoarse
      voice, thick skin with yellowish papules, including the typical disposition on
      the margin of the eyelids, infiltration of the tongue and lips, and varicella
      like scars. Histopathological examination revealed deposition of hyaline
      substance with PAS-positive diastase-resistance at the dermoepidermal junction
      and around vessels. Ultrastructural study showed considerable thickening of the
      basal lamina of vessels besides the intense deposition of amorphous material in
      the dermis. Genetic analysis was not available.

PMID- 22136865
TI  - Congenital onychogryphosis: Leaning Tower nail.
AB  - A 45-year-old man presented with a thickened and raised nail of his left fifth
      finger since birth. He was otherwise healthy. On examination, the nail of the
      left little finger was markedly thickened, hyperkeratotic, and situated at an
      angle of approximately 45 degrees to the long axis of the distal phalanx. There
      was prominent subungual hyperkeratosis. A diagnosis of congenital onychogryphosis
      of the little finger of idiopathic nature was considered. Visual analogy to the
      leaning tower of Pisa encouraged us to describe it as congenital leaning tower
      nail.

PMID- 22136867
TI  - A rare case of idiopathic neutrophilic dermatosis of the hands.
AB  - Neutrophilic dermatosis of the hands is a rare localized variant of Sweet
      syndrome. The following is a case report of a 68-year-old man who presented to
      our clinic with progressive redness, swelling, and decreased mobility of the
      fingers. Examination revealed symmetric, violaceous, edematous, annular plaques
      and nodules on the dorsal and lateral surfaces of the thumb and index fingers.
      Biopsy demonstrated a dense neutrophilic infiltrate in the papillary dermis
      without evidence of vasculitis, changes consistent with Sweet syndrome. A
      thorough work up revealed no concurrently associated condition. Treatment with
      prednisone 10 mg daily, colchicine 0.6 mg twice daily, and pentoxifylline 400 mg
      three times daily resulted in significant improvement in this case of idiopathic
      neutrophilic dermatosis of the hands.

PMID- 22136866
TI  - Disseminated histoplasmosis mimicking secondary syphilis.
AB  - A 34-year-old, HIV-positive man living in Texas presented with a 2-week history
      of fever, malaise, myalgias, oral ulcers, and papules on his chest, back, face,
      and extremities, including the palms. Initially secondary syphilis was suspected.
      However, RPR was negative. Histopathologic examination revealed a lymphocytic
      infiltrate with numerous intra-histiocytic fungal organisms. GMS and PAS stains
      were positive, consistent with the diagnosis of histoplasmosis. We report a case
      of disseminated histoplasmosis clinically mimicking secondary syphilis.

PMID- 22136868
TI  - Pigmented lesion in the inguinal region.
AB  - Pigmented Bowen disease (PBD) is a rare tumor characterized by increased melanin
      pigment in the epidermis or papillary dermis in addition to the typical findings
      of Bowen disease. We report the case of a 60-year-old woman who presented with a
      6-month history of a gradually enlarging solitary dark brown plaque in her right
      inguinal region. Histopathology showed hyperkeratosis with parakeratosis,
      acanthosis, disorganization of epidermal architecture, atypical keratinocytes,
      and increased melanin pigment of the papillary dermis. Considering the clinical
      and the histological evidence, a diagnosis of PBD was established. Complete
      resection confirmed the diagnosis. Pigmented Bowen disease is an unusual form of
      squamous carcinoma in situ. Other tumors in the differential diagnosis include
      pigmented basal cell carcinoma and superficial spreading melanoma.

PMID- 22136869
TI  - Letter: Misdiagnosis of "neurofibromatosis" in patients with piebaldism.
AB  - Miminal diagnostic criteria for the diagnosis of neurofibromatosis 1 (NF1)
      includes six or more cafe-au-lait macules plus axillary freckling. However, a
      recent report by Duarte et al claims co-occurrence of piebaldism and NF1 using
      this minimal criteria. We assert that this is not an accurate conclusion because
      both of these pigmentary findings occur frequently in typical cases of
      piebaldism.

PMID- 22136870
TI  - Letter: Adenocarcinoma of the lung associated with pityriasis rubra pilaris.
AB  - We describe a case of pityriasis rubra pilaris refractory to conventional
      treatment, found to be associated with an unrecognized primary adenocarcinoma of
      the lung. Complete resolution of the eruption followed surgical resection of the
      tumor.

PMID- 22136871
TI  - Letter: Cutaneous mastocytosis with systemic involvement mimicking clinical and
      dermatoscopically multiple melanocytic nevi.
AB  - Mastocytosis can sometimes resemble other skin conditions, especially pigmented
      ones, not only clinically but also dermatoscopically. We report the case of a
      woman with the diagnosis of cutaneous mastocytosis mimicking multiple melanocytic
      nevi. Melanocytic stimulation can be induced by high levels of stem cell factor.
      The progressive increase in the number of pigmented lesions in a patient should
      lead us to perform a biopsy to search for mastocytosis.

PMID- 22136872
TI  - Letter: Docetaxel-induced supravenous serpentine dermatitis.
AB  - Serpentine erythematous or hyperpigmented streaks along the superficial venous
      network proximal to the site of injection may occur as a distinctive eruption
      after infusion of several chemotherapeutic agents. This morphological pattern has
      been described under various terms like, "persistent supravenous erythematous
      eruption," "persistent serpentine supravenous hyperpigmented eruption," or
      "persistent serpentine supravenous hyperpigmentation." These changes belong to
      the same clinical spectrum, which most often starts as erythematous serpentine
      streaks precisely located over the injected veins; the erythema is shortly
      replaced by hyperpigmentation. We report here a case of docetaxel-induced
      supravenous serpentine dermatitis with some interesting clinical and histological
      features.

PMID- 22136873
TI  - Cluster subtypes appropriate for preventing postpartum smoking relapse.
AB  - OBJECTIVE: While the majority of women quit smoking either before or during
      pregnancy, 60 to 80% relapse in the postpartum period. The objective of this
      research was to examine postpartum women who quit smoking during their
      pregnancies and to determine the predictive factors for relapse in the postpartum
      period by identifying different subgroups that predict risk of relapse. METHOD:
      One hundred forty four postpartum women who were abstinent at the time of
      delivery were recruited. Data regarding the Acquisition Stage of Change,
      Decisional Balance and Situational Temptations to Smoke were assessed in the
      immediate postpartum period. Based on their intention to remain abstinent, 121
      women identified in the acquisition-Precontemplation (aPC) group comprised the
      study sample. Smoking status was assessed again at 2 months postpartum. RESULTS:
      A cluster analysis was performed to identify subgroups of the acquisition
      Precontemplation (aPC) group. Four subgroups were identified and were labeled
      Most Protected, Ambivalent, Risk Denial, and High Risk. Logistic regression was
      performed to establish external validity of the clusters. The clusters and
      exclusive breastfeeding were the only statistically significant variables
      associated with relapse at 2 months postpartum. CONCLUSIONS: The results
      confirmed the clusters identified in previous prevention research with both
      adolescents and postpartum women, The cluster profiles can serve to guide the
      development of a tailored intervention program.

PMID- 22136874
TI  - Initiation and persistence of alcohol use in United States Black, Hispanic, and
      White male and female youth.
AB  - BACKGROUND: The relation between early and frequent alcohol use and later
      difficulties is quite strong. However, the degree that alcohol use persists,
      which is often a necessary cause for developing alcohol-related problems or an
      alcohol use disorder, is not well studied, particularly with attention to race
      and gender. A novel statistical approach, the Multi-facet Longitudinal Model,
      enables the concurrent study of age of initiation and persistence. METHODS: The
      models were applied to longitudinal data on youth alcohol use from ages 12
      through 19, collected in the (U.S.) National Longitudinal Survey of Youth 1997
      cohort (N=8984). RESULTS: Results confirmed that Black adolescents initiate
      alcohol use at later ages than do White youth. Further, after initiation, White
      adolescents were substantially more likely than Black adolescents to continue
      reporting alcohol use in subsequent years. Hispanic teens showed an intermediate
      pattern. Gender differences were more ambiguous, with a tendency for boys to be
      less likely to continue drinking after initiation than were girls. CONCLUSIONS:
      Novel findings from the new analytic models suggest differential implications of
      early alcohol use by race and gender. Early use of alcohol might be less
      consequential for males who initiate alcohol use early, Black, and Hispanic youth
      than for their female and White counterparts.

PMID- 22136876
TI  - At the forefront of clinical neuroscience.

PMID- 22136875
TI  - Structural basis for promoter-10 element recognition by the bacterial RNA
      polymerase sigma subunit.
AB  - The key step in bacterial promoter opening is recognition of the -10 promoter
      element (T(-12)A(-11)T(-10)A(-9)A(-8)T(-7) consensus sequence) by the RNA
      polymerase sigma subunit. We determined crystal structures of sigma domain 2
      bound to single-stranded DNA bearing-10 element sequences. Extensive interactions
      occur between the protein and the DNA backbone of every -10 element nucleotide.
      Base-specific interactions occur primarily with A(-11) and T(-7), which are
      flipped out of the single-stranded DNA base stack and buried deep in protein
      pockets. The structures, along with biochemical data, support a model where the
      recognition of the -10 element sequence drives initial promoter opening as the
      bases of the nontemplate strand are extruded from the DNA double-helix and
      captured by sigma. These results provide a detailed structural basis for the
      critical roles of A(-11) and T(-7) in promoter melting and reveal important
      insights into the initiation of transcription bubble formation.

PMID- 22136877
TI  - Salmeterol or doxycycline do not inhibit acute bronchospasm and airway
      inflammation in cats with experimentally-induced asthma.
AB  - The objective of this study was to determine if inhaled salmeterol, a long-acting
      beta(2)-adrenergic agonist, and oral doxycycline, a tetracycline antibiotic
      displaying matrix metalloproteinase (MMP) inhibitory activity, reduce airway
      inflammation and obstruction in cats with experimentally-induced asthma. Eight
      Ascaris suum (AS)-sensitised cats were enrolled in a prospective study in which
      they underwent four AS-challenges at 1 month intervals. The challenged animals
      were given no treatment or were treated on 4 consecutive days with either: (1)
      oral prednisolone (1mg/kg twice daily), (2) inhaled salmeterol (50 MUg twice
      daily), or (3) oral doxycycline (5mg/kg twice daily), according to a randomised
      cross-over design. Inhibition of allergen-induced early (EAR) and late (LAR)
      asthmatic reactions were assessed by barometric whole-body plethysmography.
      Cytology and measurement of MMP-2 and -9 activities were carried out on
      bronchoalveolar lavage fluid (BALF). Although none of the treatments prevented
      the EAR, prednisolone treatment inhibited the LAR. Relative to untreated cats,
      the eosinophil percentage and MMP-2 activity in BALF were significantly reduced
      following prednisolone treatment (P<0.05). Short-term therapy with either
      salmeterol or doxycycline had no effect on the EAR or LAR or on airway
      inflammation. Given the chronic nature of this disease in cats, long-term therapy
      may be required to produce more favourable functional and clinical outcomes.

PMID- 22136878
TI  - Combination of B-Lynch brace suture and uterine artery embolization for atonic
      bleeding after cesarean section in a patient with placenta previa accreta.
AB  - We report the case of a patient with placenta previa accreta. A 29-year-old
      multipara, who had previously undergone a cesarean section, was admitted to our
      hospital for vaginal bleeding. An emergency cesarean section was carried out at
      the 33rd week of gestation. Uterine bleeding was uncontrollable, and hence,
      hysterectomy was planned. However, before hysterectomy, B-Lynch brace suture was
      carried out to control the massive bleeding; moreover, the suturing technique
      enabled uterine artery embolization to be carried out as an interventional
      radiological technique. A good postoperative course was observed, and thus, a
      secondary hysterectomy was not required. A combination of the B-Lynch brace
      suture technique and uterine artery embolization may be an alternative treatment
      for emergency bleeding during cesarean section in patients with placenta previa
      accreta.

PMID- 22136879
TI  - [Hypothalamic involvement in multiple sclerosis].
AB  - Hypothalamic involvement is a rare condition in patients with multiple sclerosis
      (MS). We report two patients with a long history of MS who presented with severe
      acute hypothermia with associated thrombocytopenia and elevated transaminase
      levels. Several cases of hypothermia or hyperthermia in patients with MS have
      been reported in the literature. They could be linked with hypothalamic lesions,
      in particular in the pre-optic area. However, other anatomical locations seem to
      be involved in thermoregulation and can be affected by MS. Besides, some cases of
      syndrome of inappropriate antidiuretic hormone secretion have been reported in
      patients with MS. Finally, some sleep disorders, particularly hypersomnia or
      narcolepsy, could be related to hypothalamic lesions, through the fall in
      hypocretin-1 in the cerebrospinal fluid. Hypocretin-1 is a neuropeptide that is
      secreted by some hypothalamic cells. It plays a role in the sleep-awake rhythm.
      We report one patient with narcolepsy and cataplexy before the first symptoms of
      MS appeared. Hypothalamic signs are rare in MS. However, several series of
      autopsies have shown a high frequency of demyelinating lesions in the
      hypothalamic area. Among these lesions, the proportion of active lesions seems
      elevated. Yet only few of them have a clinical or biological translation such as
      thermoregulation dysfunction, sleep disorders or natremia abnormalities. Thus, it
      seems unlikely that inflammatory hypothalamic lesions alone, even when bilateral,
      could be the explanation of these signs. A sufficient number of inflammatory
      demyelinating lesions, which we can observe in patients with a long history of MS
      and an already severe disability, is probably necessary to develop such a rare
      symptomatology. Hypothalamic signs might be a factor of poor prognosis for the
      disease course and progression of the disability.

PMID- 22136880
TI  - Neurological manifestations of Behcet's disease: evaluation of 40 patients
      treated by cyclophosphamide.
AB  - INTRODUCTION: Neurological manifestations in Behcet's disease represent between 4
      to 49% of systemic manifestations and remain, in the long term, the leading cause
      of morbidity and mortality. METHODS: Retrospective series of 40 severe
      Neurobehcet cases fulfilling the International Study Group criteria for Behcet's
      disease were consecutively recruited over a period from June 2004 to December
      2010. All patients had clinical and ophthalmologic examinations; they underwent
      laboratory and imaging investigations. They received corticosteroids and
      cyclophosphamide as initial bolus of 600 mg/m(2) of BSA in the 1st, 2nd, 4th, 6th
      and 8th day followed by a bolus of 600 mg/m(2) BSA every 2 months for 2 years.
      Antithrombotic therapy was given to patients with cerebral deep venous
      thrombosis. Patient follow-up and tolerance to treatment were analyzed. RESULTS:
      The average age at diagnosis was 34+/-13 years, with a sex-ratio of 1.78. The
      clinical presentation was dominated by the meningoencephalitis in 48.8% of cases,
      cerebral deep venous thrombosis in 43.6% of cases and myelopathy in 7.7% of
      cases. The 40 patients receiving cyclophosphamide bolus, despite two aggravated
      cases, evolved positively with clinical improvement and good tolerance.
      CONCLUSION: The demographic and clinical aspects of our series are similar to
      those reported in the literature. In contrast to previously reported cases of a
      poor prognosis in severe neurobehcet's disease, our study suggests that immediate
      and aggressive treatment by cyclophosphamide may ameliorate the prognosis.
      However, a multicenter study is needed to confirm the possible efficacy of
      cyclophosphamide and further assess the long-term tolerance.

PMID- 22136881
TI  - Guts, germs and glucose: understanding the effects of prematurity on the
      interaction between bacteria and nutrient absorption across the intestine.

PMID- 22136882
TI  - Metabolomic biomarkers of impaired glucose tolerance and type 2 diabetes mellitus
      with a potential for risk stratification in women with polycystic ovary syndrome.
AB  - There is a need to identify biomarkers of impaired glucose tolerance (IGT) and
      type 2 diabetes mellitus (T2DM) risk in women with PCOS to facilitate screening
      and the development of novel strategies to prevent disease progression.
      Metabolomic technologies may address this need. All published studies on
      metabolomic biomarkers of IGT and/or T2DM identified through MEDLINE (1966
      December 2010), EMBASE (1980-December 2010) and Cochrane (1993-December 2010)
      were retrieved. Eligible studies were screened and specific study characteristics
      recorded including study design, number of participants, selection criteria, type
      of metabolomic technique used, site of sample collection, and a list of
      metabolites identified to have been altered in IGT and/or T2DM versus healthy
      controls was created. Nine metabolomic biomarkers that could potentially be used
      to identify women with PCOS at risk of developing IGT and/or T2DM were identified
      including leucine, isoleucine, citrate, glucose, creatinine, valine, glutamine,
      alanine and HDL. Of these biomarkers, a panel of four biomarkers were
      consistently either elevated or reduced including glucose (elevated), valine
      (reduced), HDL (reduced) and alanine (reduced) in IGT/T2DM compared with
      controls. These biomarkers may predict the development of IGT/T2DM in young women
      with PCOS. More studies are required to test this hypothesis and translate the
      findings into patient benefit by reducing the morbidity/mortality associated with
      IGT/T2DM in PCOS.

PMID- 22136883
TI  - Vaginal cuff dehiscence after laparoscopic hysterectomy.

PMID- 22136884
TI  - Laparoscopically guided minilaparotomy: a minimally invasive approach for the
      treatment of gynaecologic diseases in morbidly obese patients.
AB  - OBJECTIVE: Obese patients are at greater risk of gynaecologic surgery. Laparotomy
      is generally performed, even though this approach is regarded as highly invasive,
      whereas laparoscopy, though minimally invasive, is relatively contraindicated
      because of the high conversion rates to laparotomy. In light of this, we propose
      laparoscopically guided transverse minilaparotomy (LGTM) as a minimally invasive
      alternative technique. The rationale of diagnostic laparoscopy is to evaluate the
      feasibility of a minimally invasive approach. We have evaluated the feasibility
      and compared the outcomes with a historical group treated with laparotomy (LPTM),
      in morbidly obese patients (MOP) subjected to gynaecologic surgery. STUDY DESIGN:
      From November 2004, MOPs with body mass index (BMI) >= 40 kg/m2 and admitted for
      gynaecologic surgery (early stage endometrial cancer and benign disease) were
      enrolled in this observational study and submitted to LGTM. Patients with a
      uterine size greater than the umbilical transverse line and with indication for
      vaginal surgery were excluded operative data and outcome were prospectively
      recorded. RESULTS: LGTM was feasible in 34 cases (87%) out of 39. In two women,
      the procedure was aborted due to intraperitoneal and ovarian malignant disease
      spread diagnosed at laparoscopy. In three cases, conversion was necessary due to
      severe adhesions in one case; laparoscopically unrecognized disease spread in the
      parametria in the second, and in the remaining case a right common iliac vein
      injury during lymphadenectomy. When compared to LPTM, haemoglobin drop and
      postoperative stay were significantly reduced with LGTM. Complications were
      higher in the control group: due to a significantly higher incidence of wound
      dehiscence (OR 0.27, 95% CI 0.05-1.32, p<0.05). CONCLUSIONS: LGTM is feasible in
      the vast majority of MOPs and achieves significantly better results when compared
      to the standard approach.

PMID- 22136886
TI  - Insights into the failure of the potential, neutral myocardial imaging agent TcN
      NOET: physicochemical identification of by-products and degradation species.
AB  - INTRODUCTION: The neutral complex [(99m)Tc(N)(NOEt)(2)], often referred to as TcN
      NOET [NOEt=N-ethoxy,N-ethyldithiocarbamate(1-)], was proposed several years ago
      as a myocardial imaging agent. Despite some favorable clinical properties
      evidenced during phase I and phase II studies, the overall results of the
      European and American phase III clinical studies have been judged insufficient
      for a successful approval process by the regulatory agencies. METHODS: Non
      carrier-added and carrier-added experiments using short-lived (99m)Tc and long
      lived (99g)Tc have been utilized to prepare a series of bis-substituted
      [Tc(N)(DTC)(2)] complexes [DTC=dithiocarbamate(1-)]. They have been purified by
      means of chromatographic techniques (high-performance liquid chromatography and
      thin-layer chromatography) and identified via double detection (UV-vis and
      radiometry) by comparison with authenticated samples of (99g)Tc compounds
      prepared by conventional coordination chemistry procedures. RESULTS: The
      molecular structure of the lipophilic, neutral complex cis-[Tc(N)(NOEt)(2)] has
      been assigned by comparison with similar nitrido-Tc(V) complexes already reported
      in the literature. Novel bis-substituted nitrido-Tc complexes containing
      hydrolyzed portions of coordinated NOEt, namely, N-ethyldithiocarbamate [NHEt(1
      )] and N-hydroxy, N-ethyldithiocarbamate [NOHEt(1-)], have been prepared and
      characterized by means of multinuclear nuclear magnetic resonance spectroscopy
      and mass spectrometry. CONCLUSIONS: Despite the identification of these
      "hydrolyzed" species, it is still unclear whether the failure to reach the
      clinical goal of the perfusion tracer [(99m)Tc(N)(NOEt)(2)] is related to the
      degradation processes evidenced in this study or is the result of the mediocre
      imaging properties of the tracer.

PMID- 22136885
TI  - Characterization of 4-[18F]-ADAM as an imaging agent for SERT in non-human
      primate brain using PET: a dynamic study.
AB  - INTRODUCTION: Serotonin transporter (SERT) has been associated with many
      psychiatric diseases. This study investigated the biodistribution of a serotonin
      transporter imaging agent, N,N-dimethyl-2-(2-amino-4-(18)F
      fluorophenylthio)benzylamine (4-[(18)F]-ADAM), in nonhuman primate brain using
      positron emission tomography (PET). METHODS: Six and four Macaca cyclopis monkeys
      were used to determine the transit time (i.e., time necessary to reach
      biodistribution equilibrium) and the reproducibility of 4-[(18)F]-ADAM
      biodistribution in the brain, respectively. The sensitivity and specificity of 4
      [(18)F]-ADAM binding to SERT were evaluated in one monkey challenged with
      different doses of fluoxetine and one monkey treated with 3,4
      methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h
      after 4-[(18)F]-ADAM intravenous bolus injection. The specific uptake ratios
      (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC)
      were calculated. RESULTS: The distribution of 4-[(18)F]-ADAM reached equilibrium
      120-150 min after injection. The mean SURs were 2.49 +/- 0.13 in MB, 1.59 +/-
      0.17 in TH, 1.35 +/- 0.06 in ST and 0.34 +/- 0.03 in FC, and the minimum
      variability was shown 120-150 min after 4-[(18)F]-ADAM injection. Using SURs and
      intraclass coefficient of correlation, the test/retest variability was under 8%
      and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75-2
      mg) dose-dependently inhibited the SURs in various brain regions. 4-[(18)F]-ADAM
      binding was markedly reduced in the brain of an MDMA-treated monkey compared to
      that in brains of normal controls. CONCLUSION: 4-[(18)F]-ADAM appears to be a
      highly selective radioligand for imaging SERT in monkey brain.

PMID- 22136887
TI  - Nonlinear compartmental model of 18F-choline.
AB  - INTRODUCTION: This work develops a compartmental model of (18)F-choline in order
      to evaluate its biokinetics and so to describe the temporal variation of the
      radiopharmaceuticals' uptake in and clearance from organs and tissues. METHODS:
      Ten patients were considered in this study. A commercially available tool for
      compartmental analysis (SAAM II) was used to model the values of activity
      concentrations in organs and tissues obtained from PET images or from
      measurements of collected blood and urine samples. RESULTS: A linear
      compartmental model of the biokinetics of the radiopharmaceutical was initially
      developed. It features a central compartment (blood) exchanging with organs. The
      structure describes explicitly liver, kidneys, spleen, blood and urinary
      excretion. The linear model tended to overestimate systematically the activity in
      the liver and in the kidney compartments in the first 20 min post-administration.
      A nonlinear process of kinetic saturation was considered, according to the
      typical Michaelis-Menten kinetics. Therefore nonlinear equations were added to
      describe the flux of (18)F-choline from blood to liver and from blood to kidneys.
      The nonlinear model showed a tendency for improvement in the description of the
      activity in liver and kidneys, but not for the urine. CONCLUSIONS: The simple
      linear model presented is not able to properly describe the biokinetics of (18)F
      choline as measured in prostatic cancer patients. The introduction of nonlinear
      kinetics, although based on physiologically plausible assumptions, resulted in
      nonsignificant improvements of the model predictive power.

PMID- 22136888
TI  - Preclinical evaluation of a 68Ga-labeled biotin analogue for applications in
      islet transplantation.
AB  - INTRODUCTION: Islet transplantation is a promising treatment for type 1 diabetes
      mellitus, but the fate of the cells after intraportal infusion is unclear. It is
      therefore imperative to develop novel techniques for noninvasive imaging and
      quantification of events following islet transplantation. METHODS: Small islet
      like microbeads, avidin-covered agarose resins (AARs), were used as a model
      system for islet transplantation. Capability for specific [(68)Ga]Ga-DOTA
      (PEG)(2)-biotin uptake and retention for either AARs or human islets conjugated
      with avidin by means of a heparin scaffold was studied in vitro. Biodistribution
      of the novel positron emission tomography (PET) tracer [(68)Ga]Ga-DOTA-(PEG)(2)
      biotin was evaluated in mice treated by intraportal transplantation of AARs by
      MUPET/computed tomography and ex vivo organ distribution and compared with
      control mice. RESULTS: AARs had high capability to bind [(68)Ga]Ga-DOTA-(PEG)(2)
      biotin, close to 50% of administrated tracer/MUl in vitro (>0.25 MBq/MUl). Avidin
      tagged human islets could bind on average 2.2% of administered tracer/MUl.
      Specificity (>90%) and retention (>90% after 1 h) were high for both AARs and
      avidin-tagged islets. Hepatic tracer uptake and retention were increased in mice
      transplanted with AARs [standardized uptake value (SUV)=2.6] compared to the
      untreated group (SUV=1.4). In vivo uptake of tracer to AARs was blocked by
      preadministration of unlabeled biotin. CONCLUSIONS: Avidin-tagged islet-like
      objects can be tracked in hepatic volume after intraportal transplantation by
      using [(68)Ga]Ga-DOTA-(PEG)(2)-biotin and PET.

PMID- 22136889
TI  - Fluorine-18 labeling of three novel D-peptides by conjugation with N-succinimidyl
      4-[18F]fluorobenzoate and preliminary examination by postmortem whole-hemisphere
      human brain autoradiography.
AB  - INTRODUCTION: beta-Amyloid (Abeta) plaques and neurofibrillary tangles are the
      main characteristics of Alzheimer's disease (AD). Positron emission tomography
      (PET), a high-resolution, sensitive, and noninvasive imaging technique, has been
      widely utilized in visualizing the localization of plaques and tangles and
      thereby distinguishing between AD and healthy controls. A small 12-mer D
      enantiomeric peptide (amino acid sequence=QSHYRHISPAQV), denoted as D1, has high
      binding affinity to Abeta in vitro in the sub-micromolar range, and consequently,
      its radiolabeled analogues have a potential as radioligands for visualizing
      amyloid plaques in vivo by PET. AIM: The aims of the present work were to develop
      three different potent D1 derivative peptides labeled with fluorine-18 and to
      examine them in the AD and control postmortem human brain by autoradiography
      (ARG). METHODS: Three different D1 derivative peptides were radiolabeled with
      fluorine-18 ([(18)F]ACI-87, [(18)F]ACI-88, [(18)F]ACI-89) using the prosthetic
      group N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB) and purified by high
      performance liquid chromatography (HPLC). Preliminary ARG measurements were
      performed in AD and control brains. RESULTS: The three fluorine-18-labeled d
      peptides were obtained in a total synthesis time of 140 min with radiochemical
      purity higher than 98%. The specific radioactivities of the three different D1
      derivative peptides were between 9 and 113 GBq/MUmol. ARG demonstrated a higher
      radioligand uptake in the cortical gray matter and the hippocampus in the AD
      brain as compared to age-matched control brain. CONCLUSIONS: Fluorine-18 labeling
      of the three novel D1 derivative peptides using [(18)F]SFB was successfully
      accomplished. Higher contrast between AD and control brain slices demonstrates
      their potential applicability for further use in vivo by PET.

PMID- 22136890
TI  - Evaluation of (111)In-labeled macrocyclic chelator-amino acid derivatives for
      cancer imaging.
AB  - PURPOSE: We evaluated new (111)In-labeled amino acid derivatives, in which the
      amino acids are conjugated with1,4,7,10-tetra-azacyclododecane-1,4,7,10
      tetraacetic acid (DOTA), 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A)
      or 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A). METHODS: DOTA
      aminoalanine (DOTA-A), DOTA-aminohomoalanine (DOTA-H), DOTA-lysine (DOTA-L), DO2A
      alanine (DO2A-A), DO3A-alanine (DO3A-A) and DO3A-homoalanine (DO3A-H) were
      labeled with (111)In. In vitro cell uptake assays were performed usingHep3B (a
      human hepatoma cell line), CT26 (a mouse colon cancer cell line) and U87MG (a
      human glioma cell line). In vitro cell uptake inhibition assays were performed
      using U87MG and (111)In-DO3A-H. U87MG bearing xenografted mice were subject to
      biodistribution, SPECT imaging, autoradiography, and immunohistochemistry
      studies. RESULTS: Of the amino acid derivatives and cell lines examined, U87MG
      and (111)In-DO3A-H showed highest uptake in vitro. This uptake was blocked by 2
      aminobicyclo-[2,2,1] heptane-2-carboxylic acid (BCH) and by tryptophan. (111)In
      DO3A-HSPECT imaging of U87MG bearing xenografted mice visualized tumors (mean
      tumor-to-muscle ratio 3.16+/-0.74). Autoradiography and immunohistochemistry
      revealed that (111)In-DO3A-H uptake matched L-type amino acid transporter 1
      expression. CONCLUSION: Tumor uptake was successfully imaged using (111)In-DO3A-H
      in U87MG bearing xenografted mice. (111)In-DO3A-H appears to be useful for
      imaging tumors expressing L-type amino acid transporter.

PMID- 22136891
TI  - Sleep-to-wake transition movement disorders.
AB  - Consciousness and vigilance level are important factors for the manifestation and
      variability of many disorders, including movement disorders. Usually lumped
      together into unspecified "Wakefulness," the transition between wakefulness and
      sleep--the pre-dormitum, and between sleep and wakefulness--the post-dormitum,
      possess intrinsic cerebral metabolic patterns and mental, behavioural, and
      neurophysiological characteristics which make these peculiar states of vigilance
      independent. Moreover, the pre- and post-dormitum, with the relative state
      dependent changes in firing patterns of many neuronal supra-pinal populations,
      act to release pacemakers responsible for different sleep-related motor
      phenomena. The relevance of pre-dormitum and post-dormitum as states different
      from full wakefulness and full sleep is, indeed, indicated by disorders which
      appear exclusively during either state, including motor disorders such as
      propriospinal myoclonus and awakening epilepsy. We will focus on three
      paradigmatic physiological/pathological motor phenomena (rhythmic movement
      disorder, hypnic jerks, and propriospinal myoclonus) strictly linked to the sleep
      wake transition periods. Thereafter we will briefly discuss how the process of
      pre-dormitum and post-dormitum can lead to such disruption of motor control.

PMID- 22136892
TI  - Pre- and post-dormitum epilepsies: idiopathic generalized epilepsies.
AB  - Epilepsy and sleep have a profound bidirectional influence. Idiopathic
      generalized epilepsy (IGE) comprises a fascinating group of syndromes that
      constitute nearly one-third of all epilepsies. These syndromes are genetically
      determined and affect otherwise normal people of both sexes and all races. IGE
      manifests with typical absences, myoclonic jerks, and generalized tonic-clonic
      seizures, alone or in varying combinations and severity. IGE syndromes are
      typically modulated by the sleep-wake cycle, and particularly by the sleep-wake
      transition process, both in terms of the occurrence of seizures and interictal
      epileptiform discharges (IED), with pronounced susceptibility to sleep
      deprivation. IGE analysis from the point of view of arousal modulation enhances
      the concept of a biological continuum existing among IGE syndromes. At the same
      time, this analysis broaches the problem of syndromic diagnosis and
      identification of the factors influencing the phenotypic expression of some
      epileptic phenomena over the course of life with potential bidirectional
      influences between epileptic manifestations and sleep-wake processes.

PMID- 22136893
TI  - Movement and behavioral disorders during sleep. Introduction.

PMID- 22136894
TI  - Arousal disorders.
AB  - Arousal Disorders (AD) are motor behaviours arising from NREM sleep. They
      comprise a spectrum of manifestations of increasing complexity from confusional
      arousal to sleep terror to sleepwalking. AD usually appear in childhood with a
      low frequency of episodes and spontaneously disappear before adolescence. The
      advent of video-polysomnography disclosed the existence of other phenomena
      alongside AD, in particular nocturnal frontal lobe seizures, requiring a
      differential diagnosis from AD. History-taking is usually sufficient to establish
      a correct diagnosis of AD even though viewing the episodes is essential for the
      clinician to distinguish the different motor events. Videopolysomnographic
      recording in a sleep laboratory is not always necessary and homemade video
      recordings are useful to capture events closest to real life episodes.

PMID- 22136895
TI  - Parasomnias and nocturnal frontal lobe epilepsy (NFLE): lights and shadows-
      controversial points in the differential diagnosis.
AB  - Nocturnal frontal lobe epilepsy (NFLE) is characterized by seizures with complex,
      often bizarre, violent behaviour arising only or mainly during sleep. These
      unusual seizures and their occurrence during sleep are often accompanied by
      normal EEG tracings and neuroradiological findings, making it difficult to
      distinguish NFLE seizures from other non-epileptic nocturnal paroxysmal events,
      namely parasomnias. NFLE was described for the first time in 1981, but, as its
      epileptic origin was controversial, the condition was called nocturnal paroxysmal
      dystonia. Even though many aspects of parasomnias and NFLE have been clarified in
      the last two decades, the problem of differential diagnosis remains a challenge
      for clinicians. This paper discusses some controversial points still under
      debate. The difficulties in distinguishing nocturnal epileptic seizures from
      parasomnias reflect just one aspect of the intriguing issue of the
      pathophysiological relationships between all types of paroxysmal motor behaviours
      during sleep.

PMID- 22136896
TI  - Agrypnia excitata.
AB  - The concept of Agrypnia excitata (AE) was originally proposed as a concept
      deriving from the clinical and anatomo-pathological observations obtained in
      three different diseases, Fatal familial insomnia (FFI), Delirium tremens (DT),
      and Morvan syndrome (MS). Agrypnia refers to a condition of severely reduced or
      absent sleep due to organic disorders. Excitata refers to the association of
      agrypnia with generalized motor and autonomic hyperactivation. AE is a syndrome
      that has been claimed to relate to a dysfunction in the thalamo-limbic circuits
      that govern sleep-wake cycles and autonomic activities.

PMID- 22136897
TI  - Epileptic motor behaviors during sleep: anatomo-electro-clinical features.
AB  - BACKGROUND: Sleep-related complex motor seizures have long been considered
      pathognomonic features of Nocturnal Frontal Lobe Epilepsy (NFLE). In recent
      years, these manifestations have also been reported to have a temporal or insular
      origin. METHOD: We describe 40 drug-resistant epileptic patients with complex
      motor seizures during sleep, submitted to presurgical stereo-EEG (SEEG)
      evaluation and seizure-free after surgical resection of the epileptogenic zone.
      RESULTS: In a significant proportion (30%) of these patients, seizures arose from
      extra-frontal regions, including mainly the temporal lobe and the insular cortex,
      but also the parietal and occipital lobes. In patients with extra-frontal
      epilepsy, when complex motor behaviors appeared, SEEG revealed that the ictal
      discharge involved the cingulate and the frontal regions. Finally, at histology,
      Taylor's focal cortical dysplasia (TFCD) was the most common finding (90% of
      patients), independent of the site of seizure onset. CONCLUSION: As previously
      reported by other studies, this histologic substrate may be a major determinant
      of sleep-related seizures in drug-resistant epileptic patients.

PMID- 22136898
TI  - Nocturnal frontal lobe epilepsy: new pathophysiological interpretations.
AB  - Since the first descriptions of Nocturnal Frontal Lobe Epilepsy (NFLE) many
      theories have been proposed to explain its pathophysiological mechanisms. The aim
      of this paper is to formulate a tentative hypothesis designed to unify the
      clinical, anatomo-physiological, and genetic aspects underlying this condition.
      According to this hypothesis, NFLE is due to a disorder in the thalamocortical
      circuit involved in the arousal mechanism. Other cortical-networks involving the
      limbic system may explain, for instance, primitive behaviors. The role of the
      cholinergic system and related pathways in the pathogenesis of nocturnal seizures
      and parasomnias is also discussed.

PMID- 22136899
TI  - Does idiopathic REM sleep behavior disorder (iRBD) really exist? What are the
      potential markers of neurodegeneration in iRBD?
AB  - REM sleep behavior disorder (RBD) may be idiopathic or associated with other
      neurologic disorders. A strong association between RBD and alpha
      synucleinopathies has recently been observed, with the parasomnia often heralding
      the clinical onset of the neurodegenerative disease. The idiopathic form accounts
      for up to 60% of the cases reported in the three largest series of patients with
      RBD. Some clinical follow-up studies revealed that a large proportion of these
      patients will eventually develop a parkinsonian syndrome or a dementia of the
      Lewy bodies type in the years following the RBD diagnosis. The estimated 10-year
      risk of neurodegenerative disease for idiopathic RBD is about 40%. Moreover, it
      has been reported that the median interval between RBD and subsequent neurologic
      syndrome is 25years. Several studies have looked at neurophysiologic and
      neuropsychological functions in idiopathic RBD and have found evidence of CNS
      dysfunction during both wakefulness and sleep in a variable proportion of these
      patients, challenging the concept of idiopathic RBD. Identifying subjects with a
      high risk of developing a neurodegenerative process may be crucial to develop
      early intervention strategies. Prospective studies in idiopathic RBD showed that
      potential markers of neurodegeneration include: (1) marked EEG slowing on
      spectral analysis; (2) decreased striatal 123I-FP-CIT binding and substantia
      nigra hyperechogenicity; (3) impaired olfactory function; (4) impaired color
      vision.

PMID- 22136900
TI  - Secondary ''incidental'' REM sleep behavior disorder: do we ever think of it?
AB  - Most secondary forms of REM sleep behavior disorder are associated with
      neurodegenerative diseases belonging to the alpha-synucleinopathies or with
      narcolepsy. However, RBD may also occur in subacute- or acute-onset conditions
      involving the central nervous system, irrespective of subjects' age and sex, and
      with or without relapse at follow-up. These conditions include structural brain
      lesions (vascular, demyelinating, tumoral, iatrogenic, etc.), CNS diseases
      (encephalitis, Guillain-Barre syndrome, etc.), forms induced by drug consumption
      or alcohol withdrawal, and possibly post-traumatic stress disorder. This review
      focuses on these forms of RBD, which are referred to as 'acute' as they occur as
      incidental phenomena within the context of other subacute- or acute-onset
      disorders. In these cases, RBD does not appear as a 'classical' clinical feature
      of the underlying condition, but rather as an intercurrent, somewhat unexpected
      phenomenon that deserves consideration in routine clinical practice, in order to
      avoid misdiagnoses and mistreatments.

PMID- 22136901
TI  - REM behaviour disorder and neurodegenerative diseases.
AB  - Rapid-eye movement (REM) sleep behaviour disorder (RBD) is an REM sleep
      parasomnia characterized by enactment of dream content during REM sleep
      associated with loss of muscle atonia. RBD can be either idiopathic or secondary
      to drugs or other diseases. The best recognized association is with
      neurodegenerative diseases, namely alpha-synucleinopathies. RBD may represent the
      first feature of neurodegeneration and can be considered an early marker of these
      disorders. This review describes the main clinical, pathogenetic, and therapeutic
      features of RBD, pointing to its association with neurodegenerative diseases and
      emphasizing the clinical and prognostic implications.

PMID- 22136902
TI  - Motor events during REM sleep in patients with narcolepsy-cataplexy: a video
      polysomnographic pilot study.
AB  - OBJECTIVE: We carried out a systematic video-polysomnographic analysis of the
      number and type of motor events during REM sleep in narcolepsy-cataplexy patients
      with REM sleep behavior disorder (NC + RBD) but not clinical RBD (NC-RBD).
      METHODS: Twelve NC + RBD and 10 NC-RBD male patients underwent video
      polysomnography (video-PSG). Motor events of different type and complexity (i.e.,
      elementary and complex movements and vocalizations) occurring during REM sleep
      were visually assessed, and indices of their frequency per hour of REM sleep were
      calculated. Subsequently, the index values were compared in NC + RBD versus NC
      RBD patients. RESULTS: Typical RBD behaviors observed in five NC + RBD patients
      were not included in any type of motor events. No objective conventional sleep
      parameter, including visual analysis of chin electromyographic (EMG) activity,
      significantly differed between the two groups of NC patients. NC + RBD patients
      showed higher occurrence of elementary movements (p = 0.034) during REM sleep
      compared with NC-RBD patients, but the occurrence of complex movements did not
      differ significantly. CONCLUSIONS: Video-analysis of motor events during REM
      sleep may improve the diagnosis of RBD in NC. RBD in NC patients is mainly
      characterized by elementary rather than complex movements, consistent with the
      view that RBD with NC patients displays a distinct phenotype with respect to
      other RBD patients.

PMID- 22136903
TI  - Oneiric stupor: the peculiar behaviour of agrypnia excitata.
AB  - Agrypnia excitata (AE) is a syndrome characterized by the inability to sleep
      associated with a generalized motor and autonomic over-activation. AE is caused
      by a thalamo-limbic system dysfunction and comprises three different conditions:
      Fatal Familial Insomnia (FFI), Delirium Tremens (DT), and Morvan Syndrome (MS).
      Oneiric Stupor episodes (OS) are the peculiar motor behaviour of AE. During OS
      patients perform simple automatic gestures mimicking daily-life activities. This
      paper is the first description of the different characteristics of OS in two
      patients with MS and another with FFI, emphasizing the specific clinical features
      that reliably differentiate OS from REM sleep behaviour disorders.

PMID- 22136904
TI  - From REM sleep behaviour disorder to status dissociatus: insights into the maze
      of states of being.
AB  - Sleep is a coordinated process involving more or less simultaneous changes in
      sensory, motor, autonomic, hormonal, and cerebral processes. On the other hand,
      none of the changes occurring with sleep are invariably coupled to sleep. EEG
      synchrony, heat loss, sleep-related hormone secretion, and even REM-related
      motoneuron paralysis may occur independent of the parent state. In REM sleep
      behaviour disorder (RBD) the muscle tone of wakefulness intrudes into REM sleep,
      allowing the release of dream-enacting behaviours. Status dissociatus (SD) is a
      condition in which brain and mind are in disarray along the boundaries of sleep
      and wakefulness. The existence of such dissociated behaviours shows that they
      have separate neuronal control systems and indicates that the whole organization
      of sleep is an emergent property of the collective neuronal systems to
      synchronize. Insults to the brain can drastically alter the circuitries
      responsible for maintaining the integrity of wakefulness, NREM sleep, and REM
      sleep. As a consequence, the basic states of existence can become admixed and
      interchanged with striking disturbances of consciousness, brain
      electrophysiology, and the behavioural and polygraphic expression of sleep and
      wakefulness. The evolution of RBD into SD may result from a disarray of
      (brainstem) structures that orchestrate the whole brain wake-sleep conditions,
      but with preserved discrete systems and dissociable strategies to still place
      navigation in wake and sleep. Advances in the fields of genetics, neuroimaging,
      and behavioural neurology will expand the understanding of the mechanisms
      underlying the organization of the states of being along with their
      somatic/behavioural manifestations.

PMID- 22136905
TI  - PEG-SO(3)H catalyzed synthesis and cytotoxicity of alpha-aminophosphonates.
AB  - One pot three-component PEG-SO(3)H catalyzed reaction of 4-(Pyridin-4
      yl)benzaldehyde and triethyl phosphite with various primary amines afforded alpha
      aminophosphonates with high yields by the Kabachnik-Field's reaction. These new
      structurally diversified set of alpha-aminophosphonates (4a-j) were evaluated for
      their anti-tumor activity on human chronic myeloid leukemia cells (K 562), human
      colon carcinoma cells (Colo 205) along with non-cancerous human embryonic kidney
      cells (HEK 293). They showed moderate activity on both cancerous cells and non
      cancerous cells.

PMID- 22136906
TI  - New N-methylpiperazinyl derivatives of bicyclic antiprotozoal compounds.
AB  - The 4-methylpiperazinyl group was inserted as substituent at the bridgehead of
      bicyclic compounds or as terminal group of their aminoacyl and aminoalkyl side
      chains. The new compounds were tested in vitro for their activities against the
      multidrug-resistant K(1) strain of Plasmodium falciparum and Trypanosoma brucei
      rhodesiense (STIB 900). The results were compared to those of formerly prepared
      analogues and of drugs in use. A couple of bicyclo-octyl omega-(4-piperazin-1
      yl)alkanoates showed high antitrypanosomal (IC(50)<=0.087MUM) and antiplasmodial
      activity (IC(50)<=0.06MUM). The most active omega-(4-methylpiperazin-1-yl)alkyl-2
      azabicyclo-nonane possessed higher antiplasmodial activity (IC(50)<=0.023MUM) and
      selectivity (S.I.=IC(50) (Cytotox.)/IC(50) (P. falciparum)=2188) than the
      antimalarial drug chloroquine (IC(50)=0.15MUM, S.I.=1257).

PMID- 22136908
TI  - Type IA choledochal cyst in adult.

PMID- 22136907
TI  - Synthesis and anticancer activity of 4beta-alkylamidochalcone and 4beta-cinnamido
      linked podophyllotoxins as apoptotic inducing agents.
AB  - A series of 4beta-alkylamidochalcone and 4beta-cinnamido linked podophyllotoxin
      congeners have been synthesized. All the twenty nine compounds were evaluated for
      anticancer activity against five human cancer cell lines (A-549, A375, MCF-7, HT
      29 and ACHN). Some of the synthesized compounds showed good anticancer activity
      that is comparable to etoposide. The IC(50) of compounds 17a and 17f is 2.7 and
      2.1 MUM respectively against A-549 cancer cell line. Flow cytometric analysis
      showed that these two compounds arrested the cell cycle in the G2/M phase leading
      to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and
      DNA fragmentation assay also suggested that 17a and 17f induced cell death by
      apoptosis.

PMID- 22136909
TI  - [The two types of auto-immune pancreatitis].
AB  - Autoimmune pancreatitis (AIP) is a rare disease (less than 5% of all chronic
      pancreatitis). AIP concept was first described 20 years ago but usual diagnostic
      criteria were published in 2006 (HISORt criteria). Since 2 years, a new AIP
      concept was described distinghing two AIP types because of differences between
      Asian and Western series. This new classification is based on pathological
      features. AIP type 1 is a systemic IgG4-related disease, defined by periductal
      lymphoplasmacytic infiltrate with obliterative phlebitis and storiform fibrosis
      and/or lymphoplasmacytic infiltrate with abundant IgG4 positive-plasma cells at
      immunostaining. AIP type 1 fits the classic description of the disease reported
      in Asian series. It appears to be a pancreatic manifestation of an IgG4
      associated systemic disease which could affect numerous organs with abundant
      infiltration of IgG4 positive-plasma cells (biliary tree, salivary glands, lymph
      nodes, retroperitoneum, kidney...), associated with elevated IgG4 serum levels.
      AIP type 2 is characterized by the presence of granulocyte epithelial lesion on
      pathological examination. The inflammatory infiltrate is usually devoid of IgG4
      positive-plasma cells and the IgG4 serum levels are normal. AIP type 2 represents
      the main pattern in Western series. No association with extra-pancreatic
      involvement has been described, except for inflammatory bowel disease (IBD) in 20
      30% of the cases. AIP diagnosis is based on association of clinical, biological
      and morphological features. MRI is essential to argue for AIP diagnosis. The
      consensual treatment is a steroid therapy (4 weeks) according to symptoms and
      relapses.

PMID- 22136910
TI  - [Psoriasis: a systemic disease].
AB  - Psoriasis is an inflammatory immune-mediated disorder which mainly affects the
      skin but which also has pathogenic effects with systemic impact. It represents a
      major psychological burden. During the past decade, inflammatory, cardiovascular,
      metabolic, and neuropsychiatric comorbidities of psoriasis have been described,
      especially in young patients with severe psoriasis. Whether psoriasis is an
      independent risk factor for these comorbidities remains a topic of scientific
      debate. Interpretation of available epidemiologic data is complex because of bias
      concerning data recruitment in the studies and non-consideration of other
      confounding risk factors and employed treatment. The hypothesis of an etiologic
      role of psoriasis in its cardiovascular and metabolic comorbidities is powered by
      pathophysiologic concepts establishing a link between chronic inflammation in
      psoriasis, endothelial dysfunction, formation of atherosclerotic plaques, and the
      different compounds of metabolic syndrome. Since psoriasis is recognized as a
      systemic disease, patient management has to be multidisciplinary. It implicates
      identification and treatment of psychological disorders, addictions, and
      associated cardiovascular and metabolic diseases. Preliminary experimental and
      epidemiological data indicate that adequate systemic treatment of psoriasis may
      prevent some comorbidities.

PMID- 22136911
TI  - Effects of weight loss and exercise on chemerin serum concentrations and adipose
      tissue expression in human obesity.
AB  - Chemerin is a chemoattractant adipokine that regulates adipogenesis and may
      induce insulin resistance. Chemerin serum concentrations are elevated in obese,
      insulin-resistant, and inflammatory states in vivo. Here we investigate the role
      of omental (OM) and subcutaneous (SC) adipose tissue chemerin and CMKLR1
      messenger RNA (mRNA) expression in human obesity. In addition, we test the
      hypothesis that changes in chemerin serum concentrations are primarily associated
      with reduced body fat mass in the context of 3 weight loss intervention studies.
      Chemerin serum concentration was measured in 740 individuals in a cross-sectional
      (n = 629) study including a subgroup (n = 161) for which OM and SC chemerin mRNA
      expression has been analyzed as well as in 3 interventions including 12 weeks of
      exercise (n = 60), 6 months of calorie-restricted diet (n = 19) studies, and 12
      months after bariatric surgery (n = 32). Chemerin mRNA is significantly higher
      expressed in adipose tissue of patients with type 2 diabetes mellitus and
      correlates with circulating chemerin, body mass index (BMI), percentage body fat,
      C-reactive protein, homeostasis model assessment of insulin resistance, and
      glucose infusion rate in euglycemic-hyperinsulinemic clamps. CMKLR1 mRNA
      expression was not significantly different between the 2 fat depots. Obesity
      surgery-induced weight loss causes a significant reduction on both OM and SC
      chemerin expression. All interventions led to significantly reduced chemerin
      serum concentrations. Decreased chemerin serum concentrations significantly
      correlate with improved glucose infusion rate and reduced C-reactive protein
      levels independently of changes in BMI. Insulin resistance and inflammation are
      BMI-independent predictors of elevated chemerin serum concentrations. Reduced
      chemerin expression and serum concentration may contribute to improved insulin
      sensitivity and subclinical inflammation beyond significant weight loss.

PMID- 22136912
TI  - ENPP1 K121Q polymorphism and type 2 diabetes mellitus in the Chinese population:
      a meta-analysis including 11,855 subjects.
AB  - Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) K121Q gene
      polymorphism has been suggested to be associated with the increased risk of
      developing type 2 diabetes mellitus (T2D), but relevant research results are
      still contradictory. To explore the relationship between ENPP1 K121Q gene
      polymorphism and T2D in the Chinese population, a meta-analysis was performed.
      Fourteen independent studies involving 11 855 subjects were retrieved from
      electronic databases. The pooled odds ratio (ORs) for the distribution of Q
      allele frequency of the ENPP1 K121Q gene and its corresponding 95% confidence
      interval (95% CI) were assessed using a random-effects model. Under an allelic
      model of inheritance, the distribution of Q allele frequency was 0.107 for the
      T2D group and 0.093 for the control group. The pooled OR for the distribution of
      Q allele frequency of ENPP1 K121Q gene was 1.29 (95% CI, 1.09-1.53;
      P(heterogeneity) = .006; I(2) = 55.6%). There was a significant association
      between ENPP1 K121Q gene polymorphism and T2D in the Chinese population (P =
      .003). Under a dominant model of inheritance, the KQ + QQ/KK value was 0.259 for
      the T2D group and 0.220 for the control group. The pooled OR for the KQ + QQ/KK
      value was 1.51 (95% CI, 1.20-1.91; P(heterogeneity) < .0001; I(2) = 71.8%). The
      association between ENPP1 K121Q gene polymorphism and T2D in the Chinese
      population followed a dominant model of inheritance (P = .0005). In the Chinese
      population, the ENPP1 K121Q gene polymorphism was implied to be involved with T2D
      susceptibility. People with the Q allele of the ENPP1 K121Q gene might be
      predisposed to T2D.

PMID- 22136913
TI  - Association between serum fibroblast growth factor 21 and diabetic nephropathy.
AB  - Fibroblast growth factor 21 (FGF-21) is a new metabolic regulator with beneficial
      effects on lipid and glucose metabolism in animal models of diabetes mellitus.
      The aim of this study was to explore the relationship between FGF-21 and diabetic
      nephropathy in humans. Serum FGF-21 levels were determined in groups of control
      (n = 50) and type 2 diabetes mellitus (T2DM) patients with normoalbuminuria (n =
      158), microalbuminuria (n = 68), and macroalbuminuria (n = 38) using enzyme
      linked immunosorbent assay. Multiple linear regression models were used to
      analyze the associations between FGF-21 or other biomedical indices and urinary
      albumin excretion (UAE). Median serum FGF-21 levels were increased in T2DM
      patients compared with nondiabetic controls and were significantly higher in
      patients of higher UAE group. In groups of control and T2DM patients with
      normoalbuminuria, microalbuminuria, and macroalbuminuria, median serum
      (interquartile range) FGF-21 levels were 467.89 (294.59-519.56), 492.30 (354.59
      640.42), 595.01 (480.49-792.31), and 665.20 (448.68-829.75) ng/L (P < .001),
      respectively. After adjustment for the confounders, FGF-21, fasting plasma
      glucose, and high-density lipoprotein cholesterol levels were found to be
      independently associated with UAE in diabetic patients. Serum FGF-21 level is
      independently correlated with UAE in T2DM patients, indicating that circulating
      FGF-21 may be involved in diabetic nephropathy.

PMID- 22136914
TI  - Surgical hemostatic agents: assessment of drugs and medical devices.
AB  - Surgical hemostatic agents are indicated to improve hemostasis when conventional
      techniques (compression, sutures or electrocoagulation) are inadequate. The
      National French Authority for Health (Haute Autorite de sante [HAS]) set out to
      assess these products (medical devices and agents) to determine their optimal
      utility. This evaluation included one class of products containing some form of
      human fibrinogen and thrombin and eight classes of medical devices and automated
      devices to prepare autologous fibrin. The assessment was based on a systematic
      review of the literature and expert opinion of health care professionals. The
      main measures of effectiveness of hemostatic agents were the success rate as
      expressed in terms of the time necessary to obtain adequate hemostasis, the
      volume of intra and/or postoperative blood loss, the need for blood transfusions,
      complication rate, duration of operations and hospital stay. A meta-analysis and
      52 controlled randomized studies were selected involving cardiac or vascular
      surgery (19), ENT surgery (11), gastrointestinal surgery (5), urology (4),
      orthopedic surgery (4). Approximately half of the studies retained in this
      analysis evaluated blood derived agents (fibrin sealants) while the other half
      evaluated medical devices. The working group considered that there is not any
      evidence that these surgical hemostatic agents decrease the rates of transfusion,
      complications, reoperation, mortality, duration of operation and/or hospital
      stay. The working group considered that the use of surgical hemostatic agents to
      improve the safety of hemostasis in the absence of identified bleeding as an
      alternative to adequate conventional hemostasis was not justified. Surgical
      hemostatic agents can be used in ad hoc settings, as a complement to conventional
      methods to control persistent bleeding after conventional hemostatic techniques,
      or when abundant bleeding has led to biologic hemostatic disorders. The working
      group also distinguished several particular settings (mouth and dental care in
      patients under antiagregant or anticoagulation therapy, central nervous system
      surgery or acute aortic dissection). Comparative data are insufficient to
      determine if one product is superior to another for a specific use. To evaluate
      the clinical value of these products, methodologically sound clinical studies are
      necessary.

PMID- 22136915
TI  - On the borderline of dissolved and particulate organic matter: partitioning and
      bioavailability of polycyclic aromatic hydrocarbons.
AB  - The functionality of dissolved organic matter (DOM) was studied by assessing the
      availability of polycyclic aromatic hydrocarbons (PAHs) spiked in pore water
      samples separated from sediments by water extraction and centrifugation with or
      without subsequent filtration. The purpose was to compare the effects of
      traditionally defined DOM (0.45-MUm cut off) and larger colloidal material
      present in the separated pore water samples on the partitioning and
      bioavailability of PAHs. The tested PAHs included phenanthrene (Phe),
      fluoranthene (Flu), pyrene (Pyr) and benzo[a]pyrene (BaP). Bioavailability of the
      selected PAHs was tested with two ecologically different organisms: pelagic
      filter feeder Daphnia magna and sediment-dwelling deposit feeder Lumbriculus
      variegatus. Sorption to DOM (i.e. in filtered samples) was clearly higher for BaP
      than for the other PAH. This was also reflected in significantly reduced
      bioavailability for both model organisms in the filtered samples compared to DOM
      free conditions. For the other PAHs the sorption was significant only in the
      unfiltered samples indicating the importance of larger colloidal material. Thus,
      the bioavailability of PAHs was also more effectively reduced by the colloidal
      material. This holds true for both the model organisms, indicating that the
      ecological differences i.e. filter feeder vs. deposit feeder do not affect in
      this respect. It appears that considering only traditionally defined DOM,
      material that may be present in environmental samples and is important for the
      speciation and bioavailability of contaminants is ignored.

PMID- 22136916
TI  - Reprogramming, in print and in person.

PMID- 22136917
TI  - Haploid embryonic stem cells and the dominance of recessive traits.
AB  - Diploidy, though essential for normal development, is a foil to geneticists. Two
      recent studies (Elling et al., 2011, this issue of Cell Stem Cell; Leeb and Wutz,
      2011, Nature), report the isolation of haploid pluripotent mouse ESCs, thus
      enabling efficient functional screening for genes involved in diverse cellular
      and developmental processes.

PMID- 22136918
TI  - Making a pituitary gland in a dish.
AB  - The adenohypophysis secretes multiple hormones that control vital physiological
      functions. A recent article in Nature (Suga et al., 2011) describes a 3D protocol
      for the derivation of several endocrine pituitary cell types from mouse ESCs.

PMID- 22136919
TI  - Epicardial origin of cardiac CFU-Fs.
AB  - The epicardium has been recognized as a source of cardiovascular progenitors
      during embryogenesis and postnatal life. In this issue of Cell Stem Cell, Chong
      et al. (2011) identify cardiac CFU-Fs as cardiac-resident cells of epicardial
      origin with broad multilineage differentiation potential.

PMID- 22136920
TI  - Blood cells need glia, too: a new role for the nervous system in the bone marrow
      niche.
AB  - Regulation of hematopoietic stem cell (HSC) dormancy by specific cell types in
      the hematopoietic niche remains poorly understood. Yamazaki et al. (2011) now
      report that nerve-associated nonmyelinating Schwann cells activate TGF-beta to
      maintain dormant HSCs, suggesting that glia are novel players in the bone marrow
      niche.

PMID- 22136921
TI  - Stem cell maintenance of the mammary gland: it takes two.
AB  - Transplantation assays suggest that multipotent stem cells maintain the two
      lineages of the mammary gland. Recently in Nature, Van Keymeulen et al. (2011)
      used lineage tracing to discover unipotent stem cells that maintain the bulk of
      the mouse mammary gland after birth and during pregnancy.

PMID- 22136922
TI  - Consternation and confusion following EU patent judgment.

PMID- 22136923
TI  - European court ruling on embryonic stem cells: ripple effects.

PMID- 22136924
TI  - Brustle decision is unhelpful, but not catastrophic.

PMID- 22136925
TI  - The European Court of Justice ruling in Brustle v. Greenpeace: the impacts on
      patenting of human induced pluripotent stem cells in Europe.

PMID- 22136926
TI  - Historical origins of transdifferentiation and reprogramming.
AB  - Transcription factor-induced reprogramming of specialized cells into other cell
      types and to pluripotency has revolutionized our thinking about cell plasticity,
      differentiation, and stem cells. The recent advances in this area were enabled by
      the confluence of a number of experimental breakthroughs that took place over the
      past 60 years. In this article, I give a historical and personal perspective of
      the events that set the stage for our current understanding of cellular
      reprogramming.

PMID- 22136927
TI  - Induced neuronal cells: how to make and define a neuron.
AB  - Cellular plasticity is a major focus of investigation in developmental biology.
      The recent discovery that induced neuronal (iN) cells can be generated from mouse
      and human fibroblasts by expression of defined transcription factors suggested
      that cell fate plasticity is much wider than previously anticipated. In this
      review, we summarize the most recent developments in this nascent field and
      suggest criteria to help define and categorize iN cells that take into account
      the complexity of neuronal identity.

PMID- 22136928
TI  - Adult cardiac-resident MSC-like stem cells with a proepicardial origin.
AB  - Colony-forming units - fibroblast (CFU-Fs), analogous to those giving rise to
      bone marrow (BM) mesenchymal stem cells (MSCs), are present in many organs,
      although the relationship between BM and organ-specific CFU-Fs in homeostasis and
      tissue repair is unknown. Here we describe a population of adult cardiac-resident
      CFU-Fs (cCFU-Fs) that occupy a perivascular, adventitial niche and show broad
      trans-germ layer potency in vitro and in vivo. CRE lineage tracing and embryo
      analysis demonstrated a proepicardial origin for cCFU-Fs. Furthermore, in BM
      transplantation chimeras, we found no interchange between BM and cCFU-Fs after
      aging, myocardial infarction, or BM stem cell mobilization. BM and cardiac and
      aortic CFU-Fs had distinct CRE lineage signatures, indicating that they arise
      from different progenitor beds during development. These diverse origins for CFU
      Fs suggest an underlying basis for differentiation biases seen in different CFU-F
      populations, and could also influence their capacity for participating in tissue
      repair.

PMID- 22136929
TI  - Erythroid/myeloid progenitors and hematopoietic stem cells originate from
      distinct populations of endothelial cells.
AB  - Hematopoietic stem cells (HSCs) and an earlier wave of definitive
      erythroid/myeloid progenitors (EMPs) differentiate from hemogenic endothelial
      cells in the conceptus. EMPs can be generated in vitro from embryonic or induced
      pluripotent stem cells, but efforts to produce HSCs have largely failed. The
      formation of both EMPs and HSCs requires the transcription factor Runx1 and its
      non-DNA binding partner core binding factor beta (CBFbeta). Here we show that the
      requirements for CBFbeta in EMP and HSC formation in the conceptus are temporally
      and spatially distinct. Panendothelial expression of CBFbeta in Tek-expressing
      cells was sufficient for EMP formation, but was not adequate for HSC formation.
      Expression of CBFbeta in Ly6a-expressing cells, on the other hand, was sufficient
      for HSC, but not EMP, formation. The data indicate that EMPs and HSCs
      differentiate from distinct populations of hemogenic endothelial cells, with Ly6a
      expression specifically marking the HSC-generating hemogenic endothelium.

PMID- 22136930
TI  - Fate restriction and multipotency in retinal stem cells.
AB  - Stem cells have the capacity to both self-renew and generate postmitotic cells.
      Long-term tracking of individual clones in their natural environment constitutes
      the ultimate way to validate postembryonic stem cells. We identify retinal stem
      cells (RSCs) using the spatiotemporal organization of the fish retina and follow
      the complete offspring of a single cell during the postnatal life. RSCs generate
      two tissues of the adult fish retina, the neural retina (NR) and the retinal
      pigmented epithelium (RPE). Despite their common embryonic origin and tight
      coordination during continuous organ growth, we prove that NR and RPE are
      maintained by dedicated RSCs that contribute in a fate-restricted manner to
      either one or the other tissue. We show that in the NR, RSCs are multipotent and
      generate all neuron types and glia. The clonal origin of these different cell
      types from a multipotent NSC has far-reaching implications for cell type and
      tissue homeostasis.

PMID- 22136933
TI  - IVIVC for circulation kinetics of liposomes.

PMID- 22136932
TI  - Reprogramming factor stoichiometry influences the epigenetic state and biological
      properties of induced pluripotent stem cells.
AB  - We compared two genetically highly defined transgenic systems to identify
      parameters affecting reprogramming of somatic cells to a pluripotent state. Our
      results demonstrate that the level and stoichiometry of reprogramming factors
      during the reprogramming process strongly influence the resulting pluripotency of
      iPS cells. High expression of Oct4 and Klf4 combined with lower expression of c
      Myc and Sox2 produced iPS cells that efficiently generated "all-iPSC mice" by
      tetraploid (4n) complementation, maintained normal imprinting at the Dlk1-Dio3
      locus, and did not create mice with tumors. Loss of imprinting (LOI) at the Dlk1
      Dio3 locus did not strictly correlate with reduced pluripotency though the
      efficiency of generating "all-iPSC mice" was diminished. Our data indicate that
      stoichiometry of reprogramming factors can influence epigenetic and biological
      properties of iPS cells. This concept complicates efforts to define a "generic"
      epigenetic state of iPSCs and ESCs and should be considered when comparing
      different iPS and ES cell lines.

PMID- 22136931
TI  - Forward and reverse genetics through derivation of haploid mouse embryonic stem
      cells.
AB  - All somatic mammalian cells carry two copies of chromosomes (diploidy), whereas
      organisms with a single copy of their genome, such as yeast, provide a basis for
      recessive genetics. Here we report the generation of haploid mouse ESC lines from
      parthenogenetic embryos. These cells carry 20 chromosomes, express stem cell
      markers, and develop into all germ layers in vitro and in vivo. We also developed
      a reversible mutagenesis protocol that allows saturated genetic recessive screens
      and results in homozygous alleles. This system allowed us to generate a knockout
      cell line for the microRNA processing enzyme Drosha. In a forward genetic screen,
      we identified Gpr107 as a molecule essential for killing by ricin, a toxin being
      used as a bioweapon. Our results open the possibility of combining the power of a
      haploid genome with pluripotency of embryonic stem cells to uncover fundamental
      biological processes in defined cell types at a genomic scale.

PMID- 22136934
TI  - Heart drugs that affect bone.
AB  - There have been important developments in our understanding of the mechanisms
      underlying the development of osteoporosis, and several of these mechanisms also
      underlie atherosclerosis. Drugs given to treat cardiovascular disease may impact
      on bone health in either a beneficial or a harmful way. There is evidence that
      nitrates are beneficial to bone, but evidence for the benefit of statins,
      thiazide diuretics, and beta-blockers is weaker. By contrast, it is likely to be
      that some drugs such as loop-acting diuretics are harmful to bone, whereas
      evidence for harm caused by drugs such as warfarin is weaker. These observations
      point towards opportunities for new drug development for bone diseases, and
      possibly the development of treatments that will benefit more than one disease.

PMID- 22136935
TI  - In quest of the missing neuron: spike sorting based on dominant-sets clustering.
AB  - Spike sorting algorithms aim at decomposing complex extracellular signals to
      independent events from single neurons in the electrode's vicinity. The decision
      about the actual number of active neurons is still an open issue, with sparsely
      firing neurons and background activity the most influencing factors. We introduce
      a graph-theoretical algorithmic procedure that successfully resolves this issue.
      Dimensionality reduction coupled with a modern, efficient and progressively
      executable clustering routine proved to achieve higher performance standards than
      popular spike sorting methods. Our method is validated extensively using
      simulated data for different levels of SNR.

PMID- 22136936
TI  - A systematic approach to embedded biomedical decision making.
AB  - An embedded decision making is a key feature for many biomedical systems. In most
      cases human life directly depends on correct decisions made by these systems,
      therefore they have to work reliably. This paper describes how we applied systems
      engineering principles to design a high performance embedded classification
      system in a systematic and well structured way. We introduce the structured
      design approach by discussing requirements capturing, specifications refinement,
      implementation and testing. Thereby, we follow systems engineering principles and
      execute each of these processes as formal as possible. The requirements, which
      motivate the system design, describe an automated decision making system for
      diagnostic support. These requirements are refined into the implementation of a
      support vector machine (SVM) algorithm which enables us to integrate automated
      decision making in embedded systems. With a formal model we establish
      functionality, stability and reliability of the system. Furthermore, we
      investigated different parallel processing configurations of this computationally
      complex algorithm. We found that, by adding SVM processes, an almost linear
      speedup is possible. Once we established these system properties, we translated
      the formal model into an implementation. The resulting implementation was tested
      using XMOS processors with both normal and failure cases, to build up trust in
      the implementation. Finally, we demonstrated that our parallel implementation
      achieves the speedup, predicted by the formal model.

PMID- 22136938
TI  - [Our congress and our journal: Dynamism and modernity].

PMID- 22136937
TI  - Bv8/PK2 and prokineticin receptors: a druggable pronociceptive system.
AB  - Mammalian Bv8 (also called prokineticin 2) is a secreted protein that regulates
      diverse biological processes including pain perception. It belongs to a new
      family of chemokines, which activate two G-protein linked receptors (prokineticin
      receptor 1 and 2, PKR1 and PKR2) expressed in regions of the nervous system
      associated with pain and in cells participating to immuno-inflammatory responses.
      Primary sensitive neurons co-express PKRs and the transient potential receptor
      vanilloid 1, cooperating in nociceptor sensitization. Bv8, strongly upregulated
      in neutrophils and other inflammatory cells, is a main pronociceptive mediator in
      inflamed tissues, where it sensitizes peripheral nociceptors, stimulates
      neutrophil chemotaxis and modulates the release of inflammatory and
      pronociceptive cytokines. Availability of a nonpeptide PKR antagonist, leading to
      blockade of the Bv8/PKR system, ameliorates pain arising from tissue injury and
      reduces the time required for recovery from injury.

PMID- 22136939
TI  - [Pandora's digital box: mental disorders in cyberspace].
AB  - The emersion of the Internet did not only change human communication and
      information seeking, it also contributed to manifold alterations in the
      manifestation, perception and treatment of mental disorders. Thus, one focus of
      current psychological research lies on the relationship between the new medium
      and psychosocial functioning. This review embraces recent results on this topic
      following a discussion from two different perspectives: first, it poses the
      question, whether the Internet - due to its very specific character - is capable
      of creating new mental disorders and second, it asks whether rare disorders may
      possibly be uncovered by the Internet or if already known disorders may be
      sustained and intensified by the online medium. Accordingly, the first part of
      this review deals with the conceptual basis of problematic Internet use, Internet
      addiction and problematic online-gaming as an example of specific internet use.
      Predisposing psychosocial factors, such as social isolation, depression and
      compulsive behavior are reviewed as potential triggers for these new internet-
      related disorders. The second part however draws upon two already existing groups
      of psychological disorders: eating disorders in relation to Pro-Ana and Pro-Mia
      on the one hand and Body Integrity Identity Disorder (BIID) on the other hand.
      Recent research is discussed to explore the sustaining and intensifying effect of
      the Internet on these disorders.

PMID- 22136940
TI  - [Raising awareness about depression together with service users and relatives -
      results of workshops for police officers in Lower Austria].
AB  - OBJECTIVE: Within the European Alliance Against Depression (EAAD), community
      mental health services inform in their service region in Lower Austria (pop.
      1.600.000) about symptoms of depression, about treatment options and service
      characteristics. Social distance can be overcome preferably by public mental
      health projects involving users and relatives. Therefore, community mental health
      services in Lower Austria routinely inform the public about depression, treatment
      options and services together with service users and relatives. This paper
      presents an evaluation of workshops for police officers. METHODS: During the year
      2010, 38 workshops for the police were conducted. All officers were asked to fill
      in the Gotland Scale of Male Depression, and to rate social distance and
      stereotypes regarding a case vignette of a fictitious depressive person. One week
      after the workshop, social distance and stereotypes were again rated. RESULTS:
      852 police officers took part in the workshops, 703 were screened by the Gotland
      Scale of Male Depression. 9 % showed depressive symptoms. The officers were
      content with the workshops, they felt better informed afterwards and thought they
      could better help affected persons. The interpretation of the case vignette was
      more often "mentally ill" or "insane". CONCLUSIONS: Personal experience with
      depression was more strongly related to present depressive symptoms than age or
      years on duty. Personal contact with a person that had been affected by
      depression before, and the slogan "depression can affect anybody" may have
      increased feelings of anxiety in officers that had taken part in the workshops.

PMID- 22136941
TI  - [Incidence and risk factors for mental abnormalities in children of psychiatric
      inpatients].
AB  - Children of mentally ill parents are exposed to a variety of stress- and harmful
      life events. To which extent the mental illness of one or both parents affects
      their children's mental development is barely studied. Therefore, over a period
      of 6 months 142 patients with children below the age of 18 (n=237 children), who
      were admitted to the Dept. for Psychiatry and Psychotherapy 1 of the Paracelsus
      Medical University Salzburg, were questioned for abnormalities in their
      children's mental development. Additionally all these patients were assessed for
      their family situation, demographic data and psychiatric disorder. 38.4% (n=91)
      of the children showed mental abnormalities. The most common one were emotional
      (n=41), social (n=41) and learning (n=34) disabilities. Parental duration of the
      illness (p=0.001), age of the children (p=0.044), illness of both parents
      (p=0.008), longlasting family conflicts (p=0.003) and living with only one parent
      (p=0.012) were correlated significantly with mental abnormalities in children.
      The results confirm an increase risk for mental abnormalities in children of
      psychiatric patients. This risk varies with existing risk and protective factors,
      which can be partially influenced. Therefore children of mentally ill parents
      with problems in their mental development should be detected early. Even if
      genetic risk factors cannot be changed reducing known psychosocial risk factors
      and promotion protective factors can significantly influence a healthy
      development of these vulnerable children.

PMID- 22136942
TI  - [Communicate instead of stigmatizing - does social contact with a depressed
      person change attitudes of medical students towards psychiatric disorders? A
      study of attitudes of medical students to psychiatric patients].
AB  - OBJECTIVE: The aim of the present study was to investigate how attitudes to
      psychiatric patients of medical students change, when given an opportunity to
      have social contact with a depressed individual, during their usual psychiatric
      practical. METHODS: In the course of their compulsory practical at the University
      Clinic for General and Social Psychiatry, 127 students additionally participated
      in an information session in which a person suffering from depression reported on
      his/her life, illness and experiences with the illness. The control group
      comprised 98 students who did only the psychiatry practical. Both at the
      beginning and end of the practical, students filled in a questionnaire, among
      others, on cognitive and affective dimensions and social distance. The
      questionnaire was preceded by 4 different case vignettes describing a fictional
      person (a man/woman suffering from paranoid schizophrenia and a man/woman
      suffering from unipolar depression). RESULTS: The results of our study show that
      before students took their practical, female students felt more pro-social and
      socially closer, but at the same time more fearful, in relation to mentally ill
      persons than male students. Females also considered psychiatric illnesses as
      better treatable than males. Basically, students felt socially closer towards
      depressed persons than towards schizophrenic patients who were also perceived to
      be more severely ill, more dangerous and more unpredictable. Students with
      personal contact with a female depressed patient during their practical
      demonstrated significant reduction of social distance and fear in relation to
      depressed persons, and in the sense of a generalization effect, there was also a
      significant reduction in their assessment of the danger and unpredictability of
      schizophrenic patients. As against this, students who did only their compulsory
      practical developed an even stronger stereotype of schizophrenic patients as
      being dangerous and unpredictable. Additionally, contact with a depressed person
      during practical resulted in a better assessment of the treatability of this
      illness. Students who participated in the compulsory practical alone reduced
      their fear towards depressed persons and increased prosocial feelings towards
      schizophrenic patients. CONCLUSIONS: Compared to students who did only the
      psychiatry practical, additional contact with a depressed person resulted in
      major changes in attitude, in particular, in relation to the stereotype of
      schizophrenic patients being "dangerous". Thus, enabling direct contact with
      patients during psychiatry practical represents a meaningful and effective anti
      stigma intervention.

PMID- 22136943
TI  - [Screening for depression in nursing homes: validity of the WHO (Five) Well-Being
      Index].
AB  - OBJECTIVE: Depression is common in nursing home residents, but is still
      underrecognized. Screening for depression could be a first step to increase
      recognition rates within this high-risk group. Therefore, we investigated the
      validity of the WHO (Five) Well-Being Index (WHO-5) for early detection of
      depression in nursing home residents. METHODS: The Structural Clinical Interview
      for DSM-IV (SCID) was used as the gold standard for the validation of the WHO-5.
      The diagnoses covered in this assessment were both current major depression as
      well as minor depression according to DSM-IV research criteria. RESULTS: In our
      sample of 92 nursing home residents in Munich aged 65-97 years, (73.9% female,
      26.1% male) 14.1% fulfilled the criteria of major depression and again 14.1%
      fulfilled the criteria of minor depression in the SCID. Overall diagnostic
      validity (area under the ROC curve) of the WHO-5 was .90 (95% confidence
      interval: .84- .97). The best cut-off-point according to Youden's index yielded a
      sensitivity of .92 and a specificity of .79. CONCLUSIONS: The diagnostic accuracy
      of the WHO-5 in our study is promising. The WHO-5 might be an efficient screening
      tool for nursing home residents, but results have to be replicated in a larger
      sample.

PMID- 22136944
TI  - [Schizophrenic psychosis with polycystic ovarian syndrome and lupus
      erythematosus].
AB  - We present the case of a patient with cycloid paranoid psychosis, polycystic
      ovarian syndrome (PCOS) and lupus erythematosus discoides, whose peculiar course
      of illness illustrates the interdependence of endocrinological, immunological and
      psychosocial factors.

PMID- 22136945
TI  - Indexation of cerebral cell membrane phospholipid catabolism by the non
      invasively determined cerebral 31-phosphorus neurospectroscopic phosphodiester
      peak.
AB  - Breakdown of mammalian cerebral cell membrane phospholipids releases
      phosphorylated polar head groups from the sn-3 phospholipid position, including
      phosphorylcholine and phosphorylethanolamine. Glycerophosphorylcholine and
      glycerophosphorylethanolamine are on their catabolic pathways and have been
      assigned to the phosphodiester narrow resonance obtained from 31-phosphorus
      neurospectroscopy, accounting for approximately 38% of the overall signal;
      therefore in human in vivo 31-phosphorus neurospectroscopy neuropsychiatric
      studies this narrow resonance has been used to index the catabolism of cerebral
      cell membrane phospholipids non-invasively. However, for ethical reasons direct
      assessment of this assumption has not hitherto been possible in humans. Recently,
      it has become possible to analyze signal directly from the cell membrane motion
      restricted phospholipids by analysis of a broad resonance signal. It was
      therefore hypothesized that there should be a negative correlation between the
      phosphodiester narrow resonance and the broad resonance signal if the former does
      indeed index cell membrane phospholipid catabolism. Cerebral 31-phosphorus
      magnetic resonance spectroscopy was carried out in 54 human subjects (mean age 38
      years; 41 male), including normal volunteers and patients with schizophrenia, in
      order potentially to widen the range of phosphodiester and broad resonance
      values. Spectra were obtained from 70 * 70 * 70 mm(3) voxels using an image
      selected in vivo spectroscopy pulse sequence. There was a highly significant
      negative correlation between the phosphodiester resonances and the broad
      resonance signals (r=-0.509, P<0.0001). This result is consistent with the
      hypothesis that the phosphodiester narrow resonance does index cell membrane
      phospholipid catabolism in non-invasive human neuropsychiatric studies.

PMID- 22136946
TI  - Dietary intake of cottonseed toxins is hypothesized to be a partial cause of
      Alzheimer's disorder.
AB  - The cause of Alzheimer's disorder is not known. The most influential known risk
      factor is increasing age. The risk factor of increasing age is consistent with
      exposure to environmental toxins throughout life as a cause of Alzheimer's. In
      addition, microbleeding, changes in membrane permeability and increased
      cholesterol are all factors important in Alzheimer's. Cottonseed contains toxins
      and is fed to animals, fish and poultry. Cottonseed toxins remain in the animals,
      fish and poultry and are present in the human diet at seemingly low levels. The
      average person is ingesting cottonseed toxins throughout life. Cottonseed toxins
      cause bleeding, changes in membrane permeability and increased cholesterol. In
      addition, the cottonseed toxin gossypol is known to reach the brain and bind
      randomly to important cellular structures. Gossypol also binds to microtubules
      and interferes with microtubule assembly, which may inhibit binding of tau to
      microtubules and lead to formation of neurofibrillary tangles. Cottonseed toxins
      are also known to accumulate in the body. In a preliminary study of female rats
      fed low level cottonseed for their lifetimes, apparent neurofibrillary tangles
      and phosphorylated tau were found. The intake of cottonseed toxins throughout
      life should be evaluated further as a possible cause of Alzheimer's.

PMID- 22136947
TI  - Is oral bisphosphonate-related osteonecrosis of the jaw an endemic condition?
AB  - Since the introduction of bisphosphonates to treat diseases that affect bone
      remodelling, there has been an increasing number of cases of bisphosphonate (BP)
      related osteonecrosis of the jaw (BRONJ). Epidemiological data regarding BRONJ
      vary widely between studies, and a number of potential methodological biases have
      been detected. In some small preliminary studies, single nucleotide polymorphisms
      associated with an increased risk of BRONJ among cancer patients have been
      identified. However, genetic susceptibility to oral BP-related BRONJ has not
      previously been discussed. We suggest that epidemiological variability could be
      related to the existence of a susceptibility factor particularly prevalent in the
      population of a well-defined geographical region. To support our hypothesis we
      performed a search for published case series, only including those with at least
      10 patients detected in a single city or a delimited geographical region; this
      showed that 55% of reports came from Mediterranean countries such as Italy,
      Israel, Spain and France. The finding does not appear to be conditioned by
      publication bias. Furthermore, conditions such as classic Kaposi sarcoma and beta
      thalassaemia, though not exclusive to the Mediterranean region, also have a high
      prevalence in that area. We speculate that some of the patients included in the
      selected US and Australian series may be of Spanish or Italian descent. With an
      ageing population, the prevalence of osteoporosis will increase, and the number
      of cases of oral BP-related BRONJ may rise exponentially. Identification of risk
      groups with susceptibility to BRONJ will arise caution when prescribing BPs and
      will allow new preventive and therapeutic strategies to be developed.

PMID- 22136948
TI  - Structure-property relationship in new photo-cured dimethacrylate-based dental
      resins.
AB  - OBJECTIVES: In this study five novel dimethacrylates of different chain lengths
      having rigid aromatic rings were synthesized and proposed as possible dental
      monomers for dental resin mixtures. METHODS: Four monomers were prepared by the
      reaction of glycidyl methacrylate with dicarboxylic acid esters obtained from
      phthalic anhydride and 1,3-propylene, 1,4-butylene, 1,5-penthylene and 1,6
      hexylene glycols. The addition reaction of glycidyl methacrylate and the acidic
      compound was carried out in the presence of tetraethylammonium bromide. The fifth
      monomer was obtained from 1,5-penthylene glycol-based dimethacrylate by blocking
      its hydroxyl groups with acetyl groups. The monomers were photo-copolymerized
      with triethyleneglycol dimethacrylate (TEGDMA) in the presence of a
      photoinitiator which was 2,2-dimethoxy-2-phenyloacetophenone. Unfilled polymers
      were evaluated for photopolymerization conversion and volumetric curing
      shrinkage. Water sorption, water solubility, flexural strength and hardness were
      measured. The prepared polymers were also subjected to dynamic mechanical studies
      (DMA). RESULTS: Results show that, increasing the distance between double bonds
      decreases flexural modulus and hardness. As expected, the curing shrinkage
      increased with increasing degree of conversion. The acetylation of hydroxyl
      groups resulted in improved water uptake properties of the compositions. It was
      demonstrated that, depending upon the content of acetyl groups in the network,
      the glass transition temperature may be significantly lowered. In polymers with
      large amounts of pendant groups, beta relaxation overlaps with alpha relaxation
      (glass transition temperature), and it is the former that discloses the maximum
      on the tandelta curve. SIGNIFICANCE: The systematic change in the length of the
      new dimethacrylates provided insight into the effects on the resultant material
      properties. It was shown in the article that the properties of the new monomers
      compare favorably with properties of the commercially available resins.

PMID- 22136949
TI  - The mechanical stability of nano-hybrid composites with new methacrylate monomers
      for matrix compositions.
AB  - OBJECTIVES: Dimer acid based metacrylates and TCD-urethane are promoted as new
      monomers of nano-hybrid resin based composites as alternatives for the
      conventional BisGMA. Investigations of this study focused on the mechanical and
      the storage behavior of nano-hybrid resin based composites (RBCs) composed of
      these new types of monomers in comparison to RBCs using BisGMA. METHODS: Flexural
      strength and modulus were determined in a three-point-bending test. Additionally,
      the modulus of elasticity was measured on microscopic scale (E(micro)) using an
      automatic microhardness indenter. Tests were performed on samples after 24 h
      storage in distilled water, as well as after thermocycling and storing the
      materials for four weeks in either distilled water, artificial saliva or ethanol.
      RESULTS: The six measured materials showed a pronounced decrease of flexural
      strength, flexural modulus and E(micro) after four weeks storage in alcohol.
      Results after four weeks storage in water and saliva could not be proven to be
      significantly different. The most sensitive factor of influence on all test
      parameters was the material. SIGNIFICANCE: Nano-hybrid composites with new or
      conventional monomers performed similar in regard to the mechanical properties
      and the behavior of the materials after aging.

PMID- 22136950
TI  - Spin evolution in a radio frequency field studied through muon spin resonance.
AB  - The application of composite inversion pulses to a novel area of magnetic
      resonance, namely muon spin resonance, is demonstrated. Results confirm that
      efficient spin inversion can readily be achieved using this technique, despite
      the challenging experimental setup required for beamline measurements and the
      short lifetime (~2.2MUs) associated with the positive muon probe. Intriguingly,
      because the muon spin polarisation is detected by positron emission, the muon
      magnetisation can be monitored during the radio-frequency (RF) pulse to provide a
      unique insight into the effect of the RF field on the spin polarisation. This
      technique is used to explore the application of RF inversion sequences under the
      non-ideal conditions typically encountered when setting up pulsed muon resonance
      experiments.

PMID- 22136951
TI  - Oscillating gradient measurements of fast oscillatory and rotational motion in
      the fluids.
AB  - We demonstrate the combination of oscillating gradient waveforms with single
      point imaging techniques to perform measurements of rapidly oscillating and/or
      rotating fluid motion. Measurements of Fourier components of motion can be
      performed over a wide range of frequencies, while the immunity of single-point
      imaging to time-evolution artefacts allows applications to systems with great
      susceptibility variations. The processing approaches, displacement resolution,
      and the diffusive attenuation are analyzed. Measurements of high-speed flow
      rotation in a spiral phantom, periodic displacements of oscillating gas in a
      thermoacoustic device and of cavitating liquid reveal a variety of motion
      spectra. The potential systems for study with the technique include turbulent
      motion, cavitation, and multiphase flows in general.

PMID- 22136952
TI  - Gastric cancer in Africa: what do we know about incidence and risk factors?
AB  - Gastric cancer is a major contributor to mortality worldwide, yet its incidence
      varies widely around the world in a way which our current understanding of
      aetiology cannot fully explain. Incidence data from Africa are weak, reflecting
      poor diagnostic resources, but there are firm data on intestinal metaplasia and
      gastric atrophy which are important steps in the carcinogenesis pathway. The
      available registry data suggest that incidence is unlikely to be dramatically
      different from Europe or North America. Helicobacter pylori infection is an
      important permissive factor in the development of cancer, but H. pylori
      seroprevalence is high all over Africa and cannot clearly be correlated with
      cancer. However, there is evidence that specific bacterial virulence genes,
      particularly vacA and iceA allele1, do contribute to cancer risk. Intestinal
      metaplasia and gastric atrophy have been the focus of twelve studies and are
      common in Africa. Epstein-Barr virus, which causes 10% of cancer worldwide, is
      the focus of only one African study. Work in other continents demonstrates that
      other risk factors apply only to one or other of the two major histological
      types, intestinal and diffuse. Diet, smoking, alcohol and salt intake predispose
      to the intestinal type of cancer, but genetic factors predispose to the diffuse
      type. There is a pressing need for information on the histological types
      occurring in Africa, and their associated risk factors. Most urgently,
      information on dietary predisposition to cancer is required to inform public
      health policy with respect to the demographic transition (urbanisation and
      lifestyle changes) which is occurring all over the continent.

PMID- 22136953
TI  - Investigation of Chagas disease in four periurban areas in northeastern Brazil:
      epidemiologic survey in man, vectors, non-human hosts and reservoirs.
AB  - Chagas disease was investigated in four periurban areas of Ceara state,
      northeastern Brazil, through serological, parasitological and molecular methods
      in humans, reservoirs and vectors. A cross-sectional survey revealed a
      seroprevalence rate of 1.2% (13/1076 residents, six also proving positive through
      PCR). Trypanosoma cruzi infection was not detected in children under 10 years
      old. Triatoma pseudomaculata prevailed in the peridomiciles: 63 specimens, 69%
      (34/49) infected with trypanosomatids. Rhodnius nasutus was captured in
      Copernicia prunifera palm trees (n=280; 25.0% infected with trypanosomatids) and
      inside dwellings (n=8, all uninfected). Trypanosoma cruzi seropositive
      reservoirs, represented by Didelphis albiventris (n=27), Rattus rattus (n=24),
      Thrichomys laurentius (n=2), Mus musculus (n=1) and Monodelphis domestica (n=1),
      were identified. Among domestic dogs (n=96) seroprevalence reached 21.9%.
      Miniexon multiplex PCR assays characterized TcI in triatomines. Both TcI and TcII
      were detected in wild mammal hosts. We conclude that Trypanosoma cruzi circulates
      within a domestic zoonotic cycle, requiring continuous surveillance. Insecticide
      application to domiciles does not appear to prevent continuous reintroduction of
      wild triatomine specimens, presenting a challenge to authorities involved in
      Chagas disease control.

PMID- 22136955
TI  - Haplotypes of heparin-binding epidermal-growth-factor-like growth factor gene are
      associated with pre-eclampsia.
AB  - AIM: Heparin-binding epidermal-growth-factor-like growth factor (HBEGF) plays an
      important role in placentation, including impaired placentation, the primary
      defect seen in pre-eclampsia. We carried out a case-control disease-association
      study to examine the association of single nucleotide polymorphisms (SNP) in the
      HBEGF gene and haplotypes defined by them with pre-eclampsia in a Sinhalese
      population in Sri Lanka. MATERIALS AND METHODS: A total of 175 women with pre
      eclampsia and 171 matched normotensive controls were genotyped for six SNP
      selected in silico as having putative functional effects using mass array
      Sequenom iplex methodology and a newly designed polymerase chain reaction
      restriction fragment length polymorphism assay. RESULTS: The individual SNP were
      not associated with pre-eclampsia. The haplotypes defined by them, however,
      showed both predisposing
      (rs13385T,rs2074613G,rs2237076G,rs2074611C,rs4150196A,rs1862176A; odds
      ratio,1.65; 95% confidence interval1.04-2.60; P=0.032) and protective
      (rs13385C,rs2074613G,rs2237076A,rs2074611C,rs4150196A,rs1862176A; odds
      ratio,0.20; 95% confidence interval, 0.04-0.89; P=0.034) effects. CONCLUSIONS:
      These results confirm that polymorphisms in the HGEGF gene are associated with
      pre-eclampsia. The haplotypes are likely to exert their effects through the
      numerous transcription regulation factors binding to the polymorphic sites,
      namely GATA-1, GATA-3, MZF-1 and AML-1a.

PMID- 22136954
TI  - Pathways of care-seeking during fatal infant illnesses in under-resourced South
      African settings.
AB  - The purpose of this study was to examine care-seeking during fatal infant
      illnesses in under-resourced South African settings to inform potential
      strategies for reducing infant mortality. We interviewed 22 caregivers of
      deceased infants in a rural community and 28 in an urban township. We also
      interviewed seven local leaders and 12 health providers to ascertain opinions
      about factors contributing to infant death. Despite the availability of free
      public health services in these settings, many caregivers utilized multiple
      sources of care including allopathic, indigenous and home treatments. Urban
      caregivers reported up to eight points of care while rural caregivers reported up
      to four points of care. The specific pathways taken and combinations of care
      varied, but many caregivers used other types of care shortly after presenting at
      public services, indicating dissatisfaction with the care they received. Many
      infants died despite caregivers' considerable efforts, pointing to critical
      deficiencies in the system of care serving these families. Initiatives that aim
      to improve assessment, management and referral practices by both allopathic and
      traditional providers (for example, through training and improved collaboration),
      and caregiver recognition of infant danger signs may reduce the high rate of
      infant death in these settings.

PMID- 22136956
TI  - New technique using an Airtraq optical laryngoscope in emergencies.

PMID- 22136957
TI  - The importance of reducing SFA intake to limit CHD risk.

PMID- 22136958
TI  - Linking early determinants and cilia-driven leftward flow in left-right axis
      specification of Xenopus laevis: a theoretical approach.
AB  - In vertebrates, laterality - the asymmetric placement of the viscera including
      organs of the gastrointestinal system, heart and lungs - is under the genetic
      control of a conserved signaling pathway in the left lateral plate mesoderm
      (LPM). A key feature of this pathway, shared by embryos of all non-avian
      vertebrate classes analyzed to date (e.g. fish, amphibia and mammals) is the
      formation of a transitory midline epithelial structure. Remarkably, the motility
      of cilia projecting from this epithelium produce a leftward-directed movement of
      extracellular liquid. This leftward flow precedes any sign of asymmetry in gene
      expression. Numerous analyses have shown that this leftward flow is not only
      necessary, but indeed sufficient to direct laterality. Interestingly, however,
      cilia-independent mechanisms acting much earlier in development in the frog
      Xenopus have been reported during the earliest cleavage stages, a period before
      any major zygotic gene transcription. The relationship between these two distinct
      mechanisms is not understood. In this review we present the conserved and
      critical steps of Xenopus LR axis formation. Next, we address the basic question
      of how an early asymmetric activity might contribute to, feed into, or regulate
      the conserved cilia-dependent pathway. Finally, we discuss the possibility that
      Spemann's organizer is itself polarized in the left-right dimension. In
      attempting to reconcile the sufficiency of the cilia-dependent pathway with
      potential earlier-acting asymmetries, we offer a general practical experimental
      checklist for the Xenopus community working on the process of left-right
      determination. This approach indicates areas where work still needs to be done to
      clarify the relationship between early determinants and cilia-driven leftward
      flow.

PMID- 22136959
TI  - rs12255372 variant of TCF7L2 gene is protective for obesity in Mexican children.
AB  - BACKGROUND AND AIMS: Variants in the transcription factor 7-like 2 (TCF7L2) gene
      are consistently associated with type 2 diabetes in adults, but the association
      of TCF7L2 with weight-related traits and body fat in humans is unclear. The aim
      of this study was to determine the relationship between the TCF7L2 gene
      (rs12255372) and obese phenotype in Mexican school-age children. METHODS: The
      study was performed in schools in Mexico City; 186 obese and 194 control children
      were studied. Fasting insulin and glucose, total cholesterol, LDL-C, HDL-C and
      triglycerides concentration were determined. The variant rs12255372 of the TCF7L2
      gene was genotyped. We used age- and sex-adjusted linear models to test for
      association with metabolic measurements with this variant. RESULTS: Genotype of
      the TCF7L2 rs12255372 gene was associated with lower fasting plasma glucose (p =
      0.001) and lower homeostasis model assessment of insulin resistance (HOMA-R; p =
      0.001) in nonobese children. Heterozygous carriers for this variant were more
      prevalent in lean children (32.5%) than in the obese group (23.7%), which
      resulted in a strong protective effect for the normal weight condition (OR =
      0.56, 0.32-0.97). CONCLUSIONS: TCF7L2 rs12255372 polymorphism protects Mexican
      children from obesity. Further research in other large, population-based studies
      is needed to replicate these findings.

PMID- 22136960
TI  - Supplementation of n3 long-chain polyunsaturated fatty acid synergistically
      decreases insulin resistance with weight loss of obese prepubertal and pubertal
      children.
AB  - BACKGROUND AND AIMS: Supplementation with n3 long-chain polyunsaturated fatty
      acids (n3-LCPUFA) appears to affect body weight, adipokines, and insulin
      resistance (IR) in obese individuals. However, it is unclear whether the effect
      on IR is independent of weight loss and if the same effect is observed in
      children. We undertook this study to analyze the effect of supplementation with
      n3-LCPUFA on adipokine concentration and IR of prepubertal and pubertal children,
      independent of weight loss. METHODS: Included were 76 children, 9- to 18-years of
      age. Subjects were overweight and insulin resistant, but otherwise healthy. They
      were randomly assigned to receive 900 mg n3-LCPUFA daily (Omega III, Salmon Oil,
      GNLD) or placebo for 1 month. No dietary intervention was conducted. Dietary
      information, anthropometry, and blood samples to measure adipokines and IR were
      obtained at baseline. Anthropometry and measurement of biochemical parameters
      were repeated at the end of follow-up. For analysis, children were stratified by
      treatment (placebo and n3-FA) and according to changes in body weight (increase,
      decrease, unchanged). RESULTS: Twenty seven children received placebo and 49
      received the n3-LCPUFA. Despite no differences at baseline, only the n3-FA group
      decreased fasting insulin and HOMA-IR (p <0.010). Significant differences between
      groups were observed for changes in TNF-alpha, leptin and adiponectin after
      supplementation (p <0.050). At the end of the 1-month period, 16 children lost
      weight and 27 children gained weight. Multiple analysis demonstrated that
      supplementation with n3-LCPUFA decreased HOMA-IR by 15% after adjusting for
      puberty, treatment adherence, changes in adipokines, and weight loss. Interaction
      between supplementation and weight loss was significant (p = 0.007). CONCLUSIONS:
      Supplementation with n3-LCPUFA is a potential beneficial tool for obese at-risk
      children.

PMID- 22136961
TI  - The search for a practice model to reduce miscarriage after assisted
      reproduction.
AB  - The analysis of 52,874 clinical pregnancies recorded on the Australian and New
      Zealand Assisted Reproduction Database (ANZARD) between 2004 and 2008 showed that
      maternal age and obstetrics history are closely related to the risk of
      miscarriage, and that the transfer of fresh embryos is associated with fewer
      miscarriages than transfer of frozen-thawed embryos. It also suggested a higher
      miscarriage rate is associated with the transfer of thawed blastocysts compared
      with transfer of thawed cleavage-stage embryos or the blastocysts that ensued
      from them. Therefore, the authors proposed a practice model of transferring fresh
      blastocysts and freezing of cleavage-stage embryos to reduce the miscarriage rate
      after assisted reproduction. This model may have practical limitation and would
      need validation in a randomized trial. Retrospective analysis of large national
      databases is useful in identifying trends and generating hypothesis, but
      evaluation of these hypotheses in randomized trials remains necessary for
      objective validation.

PMID- 22136964
TI  - Are polycyclic aromatic hydrocarbons from fossil emissions potential hormone
      analogue sources for modern man?

PMID- 22136963
TI  - Pre-treatment with an intravenous lipid emulsion containing fish oil
      (eicosapentaenoic and docosahexaenoic acid) decreases inflammatory markers after
      open-heart surgery in infants: a randomized, controlled trial.
AB  - BACKGROUND & AIMS: This study assessed the effects of administering a lipid
      emulsion containing eicosapentaenoic and docosahexaenoic acid before and after
      open-heart surgery on cytokine production and length of hospital stay in infants.
      METHODS: Thirty-two infants (40 +/- 2.3 weeks gestational age; 10.6 days at time
      of surgery) undergoing open-heart surgery with cardiopulmonary bypass were
      randomized to receive an intravenous lipid emulsion with (treatment) or without
      (control) eicosapentaenoic and docosahexaenoic acid in this prospective,
      randomized, double-blind, controlled trial. RESULTS: Mean plasma TNF-alpha
      concentration was significantly (p = 0.003) lower in the treatment (5.9 pg/mL)
      compared to the control group (14.8 pg/mL). In infants without sepsis, plasma TNF
      alpha did not differ according to treatment, however when sepsis developed, mean
      plasma TNF-alpha was 21.1 pg/mL and 1.5 pg/mL (p = 0.0007) in control and
      treatment groups, respectively. Plasma TNF-alpha was positively correlated with
      length of hospital stay in the control group (p = 0.01), and negatively
      correlated with length of stay in the treatment group (p = 0.004), with a
      significant time by treatment interaction (p = 0.02). CONCLUSIONS: Providing a
      lipid emulsion containing eicosapentaenoic and docosahexaenoic acid reduces TNF
      alpha concentrations in infants undergoing open-heart surgery. Lipid emulsions
      containing eicosapentaenoic and docosahexaenoic acid may ameliorate the
      inflammatory response among critically ill infants.

PMID- 22136965
TI  - Local diagnostic reference levels for typical radiographic procedures.
AB  - PURPOSE: To establish local diagnostic reference levels (DRL) for typical
      radiographic examinations in a fully digital imaging institution. METHODS: The
      initial survey included 6 standard radiographic projections performed in 19
      computed radiography (CR) and digital radiography (DR) rooms. Because of the
      expected difference in the performance, the local reference levels were analysed
      separately for those 2 modalities. Data of 226 average size adult patients were
      included in the analysis. Entrance surface dose (ESD) was calculated from the
      recorded radiographic techniques and tube radiation output measurements. After
      observing wide variations in the results of the patient survey, the examinations
      were repeated by using anthropomorphic phantoms. Initial efforts to understand
      the reasons for dose variations were focused on CR chest, abdomen, pelvis, and
      lumbar spine examinations. RESULTS: The average size patient doses for similar
      examinations were lower in the DR rooms than in the CR rooms by factors that
      ranged from 1.2 to 3, with the exception of the chest examination.
      Standardization of the CR exposure index value allowed us to decrease ESD by 21%
      30%. Detector sensitivity had an insignificant effect (2%) on ESD; proper
      collimation lowered the dose by 17%. However, the major effect, up to 46%
      difference, was found because of antiscatter grids cutoff. CONCLUSION: Modality
      specific local diagnostic reference levels for standard examinations have been
      established in a large digital imaging department with hybrid modalities.
      Typically the local reference values were lower than those recommended in Safety
      Code 35, except for CR chests. Factors that affect the dose variations have been
      investigated and determined.

PMID- 22136966
TI  - Preoperative breast magnetic resonance imaging: applications in clinical
      practice.
AB  - Results of large randomized trials have shown that survival rates after breast
      conserving surgery are equivalent to those obtained by radical mastectomy. Breast
      conserving surgery with wide local excision in women with early stage breast
      cancer who are thought to have a single and resectable tumour as determined by
      clinical examination and conventional imaging followed by postoperative
      irradiation is the standard of care in early breast cancer. Mapping of local
      disease is the key element to guide optimal surgery to obtain tumour-free
      margins, thereby decreasing risk of local recurrence. The usual preoperative
      workup of breast malignancy consists of clinical breast examination and
      mammography with or without ultrasound. However, mammography and ultrasound fail
      to accurately assess tumour extent in as many as a third of patients eligible for
      breast conserving therapy. It is well established that magnetic resonance imaging
      is far superior to mammography (with and without ultrasound) for mapping the
      local extent of breast cancer. Experts advocate its use despite its high costs,
      high number of false positive findings, and lack of evidence from randomized
      prospective trials and, notably, fear of "overtreatment." This article discusses
      the current role of breast magnetic resonance imaging with its clinical
      advantages and applications.

PMID- 22136967
TI  - Incremental value of computed tomography in triaging emergency department
      patients with acute chest pain.

PMID- 22136968
TI  - The relationship of body mass index and abdominal fat on the radiation dose
      received during routine computed tomographic imaging of the abdomen and pelvis.
AB  - PURPOSE: To determine the relationship of increasing body mass index (BMI) and
      abdominal fat on the effective dose acquired from computed tomography (CT)
      abdomen and pelvis scans. METHODS: Over 6 months, dose-length product and total
      milliamp-seconds (mAs) from routine CT abdomen and pelvis scans of 100 patients
      were recorded. The scans were performed on a 64-slice CT scanner by using an
      automatic exposure control system. Effective dose (mSv) based on dose-length
      product, BMI, periumbilical fat thickness, and intra-abdominal fat were
      documented for each patient. BMI, periumbilical fat thickness, and intra
      abdominal fat were compared with effective dose. RESULTS: Thirty-nine men and 61
      women were included in the study (mean age, 56.3 years). The mean BMI was 26.2
      kg/m(2). The mean effective dose was 10.3 mSv. The mean periumbilical fat
      thickness was 2.4 cm. Sixty-five patients had a small amount of intra-abdominal
      fat, and 35 had a large amount of intra-abdominal fat. The effective dose
      increased with increasing BMI (P < .001) and increasing amounts of intra
      abdominal fat (P < .001). For every kilogram of weight, there is a 0.13 mSv
      increase in effective dose, which is equal to 6.5 chest radiographs per CT
      examination. For an increase in BMI by 5 kg/m(2), there is a 1.95 mSv increase in
      effective dose, which is equal to 97.5 chest radiographs per CT examination.
      CONCLUSION: Increasing BMI and abdominal fat significantly increases the
      effective dose received from CT abdomen and pelvis scans.

PMID- 22136969
TI  - Thyroid incidentalomas on fluorine-18-fluorodeoxyglucose positron emission
      tomography-computed tomography: incidence, malignancy risk, and comparison of
      standardized uptake values.
AB  - INTRODUCTION: To determine the incidence of fluorine-18-fluorodeoxyglucose (FDG)
      avid thyroid incidentalomas detected on positron emission tomography (PET) with
      integrated computed tomography (CT), and correlate the FDG-PET-CT findings to
      cytology. METHODS: A total of 942 FDG-PET-CT reports were retrospectively
      reviewed. Patients with FDG-avid thyroid incidentalomas were further reviewed for
      correlative cytology. RESULTS: The incidence of FDG-avid thyroid incidentalomas
      is 2.2%. Thyroid malignancies were identified in 3 of 6 patients who underwent
      cytologic correlation, with a positive predictive value of 50% (95% confidence
      interval, 14%-86%). The mean maximum standardized uptake values of benign and
      malignant FDG-avid thyroid incidentalomas were 5.6 and 6.6, respectively.
      CONCLUSION: A FDG-avid thyroid incidentaloma may predict underlying malignancy.
      Cytologic assessment should be considered for FDG-avid thyroid incidentalomas.

PMID- 22136970
TI  - Cochlear implant in patients with sudden unilateral sensorineural hearing loss
      and associated tinnitus.
AB  - INTRODUCTION AND OBJECTIVES: To assess the efficacy of cochlear implantation in
      patients with unilateral sudden sensorineural hearing loss and associated
      disabling tinnitus. METHODS: Ten patients suffering from severe-to-profound
      sudden hearing loss and tinnitus in the affected ear received implants. The
      sample was comprised of 4 men and 6 women, with a mean age of 42.7 years (range
      34-62) at implantation. The severity of the tinnitus was evaluated with the
      Spanish validated version of the Tinnitus Handicap Inventory (THI) and a visual
      analogue scale. These assessments were obtained before and after implantation.
      RESULTS: Tinnitus suppression was observed in 2 patients. In 7 cases, we observed
      an improvement in the THI, in different degrees, and 1 patient remained without
      changes. Tinnitus worsening was not found in the series studied. CONCLUSIONS:
      Tinnitus reduction following cochlear implantation can be explained by several
      mechanisms, such as habituation, acoustic masking, direct stimulation of the
      cochlear nerve and reorganisation of cortical areas. Even though further research
      is required, cochlear implantation is an effective method for the treatment of
      disabling tinnitus in patients with severe-to-profound unilateral sudden
      sensorineural hearing loss.

PMID- 22136971
TI  - Elemental analysis of glass by laser ablation inductively coupled plasma optical
      emission spectrometry (LA-ICP-OES).
AB  - The elemental analysis of glass evidence has been established as a powerful
      discrimination tool for forensic analysts. Laser ablation inductively coupled
      plasma optical emission spectrometry (LA-ICP-OES) has been compared to laser
      ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and energy
      dispersive micro X-ray fluorescence spectroscopy (MUXRF/EDS) as competing
      instrumentation for the elemental analysis of glass. The development of a method
      for the forensic analysis of glass coupling laser ablation to ICP-OES is
      presented for the first time. LA-ICP-OES has demonstrated comparable analytical
      performance to LA-ICP-MS based on the use of the element menu, Al (Al I 396.15
      nm), Ba (Ba II 455.40 nm), Ca (Ca II 315.88 nm), Fe (Fe II 238.20 nm), Li (Li I
      670.78 nm), Mg (Mg I 285.21 nm), Sr (Sr II 407.77 nm), Ti (Ti II 368.51 nm), and
      Zr (Zr II 343.82 nm). The relevant figures of merit, such as precision, accuracy
      and sensitivity, are presented and compared to LA-ICP-MS. A set of 41 glass
      samples was used to assess the discrimination power of the LA-ICP-OES method in
      comparison to other elemental analysis techniques. This sample set consisted of
      several vehicle glass samples that originated from the same source (inside and
      outside windshield panes) and several glass samples that originated from
      different vehicles. Different match criteria were used and compared to determine
      the potential for Type I and Type II errors. It was determined that broader match
      criteria is more applicable to the forensic comparison of glass analysis because
      it can reduce the affect that micro-heterogeneity inherent in the glass fragments
      and a less than ideal sampling strategy can have on the interpretation of the
      results. Based on the test set reported here, a plus or minus four standard
      deviation (+/- 4s) match criterion yielded the lowest possibility of Type I and
      Type II errors. The developed LA-ICP-OES method has been shown to perform
      similarly to LA-ICP-MS in the discrimination among different sources of glass
      while offering the advantages of a lower cost of acquisition and operation of
      analytical instrumentation making ICP-OES a possible alternative elemental
      analysis method for the forensic laboratory.

PMID- 22136972
TI  - Stent longitudinal integrity bench insights into a clinical problem.
AB  - OBJECTIVES: Standardized bench-top compression and elongation testing was
      undertaken to assess the longitudinal strength of contemporary stents. Insights
      gained may improve clinical stent choice and deployment techniques, and
      facilitate future stent design improvements. BACKGROUND: The hoops of coronary
      stents provide radial support, and connectors hold hoops together. Strut
      material, shape, and thickness, along with connector number and configuration,
      provide the balance between stent flexibility and longitudinal integrity.
      Longitudinal distortion manifests as length change, strut overlap, strut
      separation, malapposition, and luminal obstruction. These may predispose to
      restenosis and stent thrombosis, obstruct passage of devices, be misinterpreted
      as strut fracture, and require additional stenting. METHODS: The force required
      to compress and to elongate 7 contemporary stents was measured with an Instron
      universal testing machine (Norwood, Massachusetts). Stents deployed in a silicone
      phantom damaged by a balloon or guide catheter were imaged by microcomputed
      tomography to understand better the appearances and effects of longitudinal
      distortion. RESULTS: Stents with 2 connectors (Boston Scientific [Natick,
      Massachusetts] Omega and Medtronic [Santa Rosa, California] Driver) required
      significantly less force to be compressed up to 5 mm and elongated by 1 mm than
      designs with more connectors. The 6-connector Cypher Select required
      significantly more force to be elongated 5 mm than other designs. CONCLUSIONS:
      Stents with 2 connectors between hoops have less longitudinal strength when
      exposed to compressing or elongating forces than those with more connectors. This
      independent, standardized study may assist stent selection in clinical situations
      where longitudinal integrity is important, and may aid future design
      improvements. Stent longitudinal strength, the resistance to shortening or
      elongation, appears related to the number of connectors between hoops. Using a
      standardized testing protocol, designs with 2 connectors were more likely to
      shorten or elongate than those with more connectors. Distortion may be recognized
      clinically as bunching or separation of struts, and may be confused with strut
      fracture. Without post-dilation or further stent deployment, the patient may be
      at increased risk for adverse clinical events. A stent design change ensuring 3
      connectors, especially at the proximal end of a stent, should increase
      longitudinal integrity, but perhaps at the expense of stent flexibility.

PMID- 22136973
TI  - Dye-assisted lymphatic-sparing laparoscopic varicocelectomy in children.
AB  - INTRODUCTION: The ideal method for varicocelectomy in children remains
      controversial. We present our experience with dye-assisted lymphatic-sparing
      laparoscopic varicocelectomy (LSLV) in children, which overcomes the limitations
      of previously described techniques. MATERIALS AND METHODS: Twenty-five
      consecutive LSLVs were performed on children with a mean age of 15 years over a 4
      year period. Varicocele grade was 3 in 21 cases and grade 2 in 4. Indications for
      intervention were hypotrophy in 12, pain in 11 cases and family preference in 2.
      A scrotal injection of lymphatic dye was utilized to spare at least one lymphatic
      and the remaining spermatic vessels were divided. RESULTS: Lymphatic sparing was
      accomplished in all cases. Operative time varied from 30 to 140 min (mean 85 +/-
      26). No perioperative complications were noted. On average follow-up of 13 months
      a residual varicocele was noted in 2 cases, with no hydrocele and resolution of
      pain. Mean testicular volume difference diminished from 33% pre to 18%
      postoperatively. CONCLUSION: This multi-surgeon experience demonstrates that dye
      assisted LSLV is easily accomplished with promising results. It appears that
      preservation of a single spermatic lymphatic vessel is sufficient, although in
      some cases a second dye injection is required to visualize the lymphatics.

PMID- 22136974
TI  - High plasma CXCL10 levels are associated with HCV-genotype 1, and higher insulin
      resistance, fibrosis, and HIV viral load in HIV/HCV coinfected patients.
AB  - BACKGROUND: CXCL10 may contribute to the host immune response against the
      hepatitis C virus (HCV), liver disease progression, and response to HCV antiviral
      therapy. The aim of our study was to analyze the relationship among virological,
      immunological, and clinical characteristics with plasma CXCL10 levels in human
      immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We carried out a
      cross-sectional study on 144 patients. CXCL10 and insulin were measured using an
      immunoassay kit. The degree of insulin resistance was estimated for each patient
      using the homeostatic model assessment (HOMA) method. Insulin resistance was
      defined as a HOMA index higher than or equal to 3.8. Aspartate aminotransferase
      (AST) to platelet ratio (APRI), FIB-4, Forns index, HGM1, and HGM2 were
      calculated. RESULTS: The variables associated with log(10) CXCL10 levels by
      univariate analysis were age (b=0.013; p=0.023), prior AIDS-defining condition
      (b=0.127; p=0.045), detectable plasma HIV viral load (b=0.092; p=0.006), log(10)
      HOMA (b=0.216; p=0.002), HCV-genotype 1 (b=0.114; p=0.071), and liver fibrosis
      assessed by all non-invasive indexes (log(10) APRI (b=0.296; p=0.001), log(10)
      FIB-4 (b=0.436; p<0.001), log(10) Forns index (b=0.591; p<0.001), log(10) HGM1
      (b=0.351; p=0.021), and log(10) HGM2 (b=0.215; p=0.018)). However, in
      multivariate analysis, CXCL10 levels were only associated with HOMA, detectable
      plasma HIV viral load, HCV-genotype 1 and FIB-4 (R-square=0.235; p<0.001).
      CONCLUSION: Plasma CXCL10 levels were influenced by several characteristics of
      patients related to HIV and HCV infections, insulin resistance, and liver
      fibrosis, indicating that CXCL10 may play an important role in the pathogenesis
      of both HCV and HIV infections.

PMID- 22136975
TI  - Early release of macrophage migration inhibitory factor after liver ischemia and
      reperfusion injury in rats.
AB  - Macrophage migration inhibitory factor (MIF) is an important mediator of
      ischemia/reperfusion (I/R) injury in heart, brain and intestine. We previously
      demonstrated that MIF was released during warm/cold ischemia in vitro. However,
      the role of MIF in liver I/R injury remains unclear. We aimed to test the
      hypothesis that MIF acts as an early proinflammatory cytokine and could mediate
      the inflammatory injury in liver I/R. Rats (n=6 per group) were subjected to 90
      min warm ischemia followed by 0.5h, 6h and 24h reperfusion, respectively to liver
      transplantation (LTx) after 6h of cold ischemia followed by 24h of reperfusion.
      The expression of MIF, its receptor (cluster of differentiation 74 (CD74)) and
      the downstream inflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-1 beta (IL-1beta)) were analyzed. Peritoneal macrophages were
      cultured for 6h alone or in the presence of effluent from cold-preserved livers
      or effluent depleted of MIF. Warm I/R increased hepatic MIF-mRNA and protein
      expression. MIF-protein was released into peripheral circulation in vivo with a
      maximum at 0.5h after reperfusion. Induction of MIF-expression was associated
      with the expression of proinflammatory cytokines and its receptor in both models.
      MIF released by isolated cold preserved livers, induced TNF-alpha and IL-1beta
      production by cultured peritoneal macrophages. Intrahepatic upregulation of MIF,
      release into systemic circulation and the associated upregulation of the
      proinflammatory mediators suggest a role of MIF in mediating the inflammatory
      response to I/R injury. Blocking experiments will help to elucidate its role as
      potential molecular target for preventing hepatic I/R injury.

PMID- 22136976
TI  - Tadalafil and pulmonary arterial hypertension.

PMID- 22136977
TI  - Characteristics of successful recruitment in prospective pediatric
      pharmacogenetic studies.
AB  - BACKGROUND: There is a need to explore feasible means of accruing an appropriate
      study cohort to help fill the knowledge gap between pharmacogenetic contributions
      to drug response and clinical application in the pediatric population.
      OBJECTIVES: The aim of this study was to identify factors affecting recruitment
      of eligible subjects in pharmacogenetic studies at a large Midwestern pediatric
      academic medical center. The objectives were to evaluate recruitment success of
      ongoing trials and ascertain contributors to differential recruitment rates. We
      hypothesized that studies with good recruitment of eligible subjects would share
      characteristics not present in studies with lower than anticipated recruitment.
      The goal was to better understand barriers to good recruitment in pharmacogenetic
      studies to help inform future trial and infrastructure design. METHODS:
      Investigators designed a survey with proposed elements of success, which was then
      completed by lead and/or site investigators of all pharmacogenetics studies at
      the institution. Results were evaluated using an investigator-developed
      likelihood of success scoring system. RESULTS: Two studies recruited >95% of the
      approached eligible patients; 4 studies were consistent with investigator
      anticipated recruitment (>50%), and 1 study did not meet expected recruitment. A
      study's total score on the investigator-devised scoring tool correlated well with
      the proportion of approached patients recruited (Pearson's correlation, r = 0.82;
      P < 0.001). Multiple factors impacted successful recruitment into these
      pharmacogenetic studies. Features of studies with successful recruitment included
      standardized clinical care, an ongoing team-patient relationship, severe and/or
      life-threatening outcome measures, study coordinator with experience in clinical
      research, a study medication with few or no alternative treatment options, and
      active involvement of the research team in clinical care. CONCLUSIONS: A scoring
      system for study characteristics may be useful to calculate the risk of failure
      for successful recruitment, allow discrimination among characteristics
      contributing to the risk, and permit study design alterations to improve
      likelihood of successful recruitment in pediatric pharmacogenetic studies.

PMID- 22136978
TI  - Comparative efficacy and safety profile of amlodipine 5 mg/losartan 50 mg fixed
      dose combination and amlodipine 10 mg monotherapy in hypertensive patients who
      respond poorly to amlodipine 5 mg monotherapy: an 8-week, multicenter,
      randomized, double-blind phase III noninferiority study.
AB  - BACKGROUND: The number of hypertensive patients achieving treatment targets is
      not ideal with therapies that engage a single mechanism of action, and
      combination therapies using different mechanisms of action can increase drug
      efficacy in a synergistic way. OBJECTIVE: This noninferiority study compared the
      clinical efficacy and safety profile of fixed-dose combination of
      amlodipine/losartan 5/50 mg and amlodipine 10 mg monotherapy in essential
      hypertensive patients who respond poorly to amlodipine 5 mg monotherapy. METHODS:
      This was a double-blind, multicenter, randomized trial of hypertensive patients
      (N = 185) aged >=18 years taking amlodipine 5 mg during the run-in treatment
      period but failed to achieve sitting diastolic blood pressure (DBP) <90 mm Hg.
      After randomization into the amlodipine/losartan 5/50 mg fixed-dose combination
      group (n = 92) and the amlodipine 10 mg monotherapy group (n = 93), treatment was
      maintained without dose escalation for 8 weeks. The noninferiority margin was
      prespecified as 4 mm Hg after 8 weeks of treatment for the difference of the
      average change in DBP between treatments. The primary efficacy evaluation of
      noninferiority was tested using a confidence interval approach with a 97.5% 1
      sided lower confidence limit using the average difference in DBP measured at
      baseline and 8 weeks. RESULTS: After 8 weeks, the DBP of both groups decreased
      from baseline by 8.9 (6.1) and 9.4 (7.5) mm Hg, respectively (difference = -0.5
      [6.9] mm Hg, 95% CI: -2.5 to 1.5). Secondary end points of reductions in DBP
      after 4 weeks (-8.1 [6.7] vs -9.9 [7.3] mm Hg, difference = -1.8 mm Hg, 95% CI: 
      3.9 to 0.2) and sitting systolic blood pressure after 4 (-10.2 [11.8] vs -12.8
      [10.2] mm Hg, difference = -2.6 mm Hg, 95% CI: -5.9 to 0.6) and 8 weeks (-12.2
      [11.0] vs -13.4 [11.3] mm Hg, difference = -1.2 mmHg, 95% CI: -4.4 to 2.1) were
      comparable between the 2 treatment groups. There were 38 adverse events in 20
      patients (21.7%) in the amlodipine/losartan 5/50 mg fixed-dose combination group
      and 31 in 24 patients (26.1%) in the amlodipine 10 mg monotherapy group; most
      were mild. There were 7 adverse events in 6 patients (6.5%) related to treatment
      in the fixed-dose combination group and 13 in 10 patients (10.9%) in the
      monotherapy group (P = 0.30). CONCLUSIONS: Fixed-dose combination
      amlodipine/losartan 5/50 mg was not inferior in terms of reductions in DBP after
      8 weeks of treatment and had comparable safety profile to amlodipine 10 mg in
      patients who did not respond to amlodipine 5 mg monotherapy. ClinicalTrials.gov
      identifier: NCT00940667.

PMID- 22136979
TI  - Noninsulin treatment of type 2 diabetes mellitus in geriatric patients: a review.
AB  - BACKGROUND: Currently, 42% of the US population with diabetes is aged >=65 years.
      OBJECTIVE: The aim of this review was to discuss the efficacy and tolerability of
      noninsulin therapies for type 2 diabetes mellitus (T2DM), with an emphasis on
      patients aged >=65 years. METHODS: PubMed and EMBASE (1977-2010) were searched
      using the terms geriatric, elderly patients, type 2 diabetes mellitus, metformin,
      secretagogues, thiazolidinediones (TZDs), alpha-glucosidase inhibitors,
      dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1)
      receptor agonists. Articles were included if they were clinical trials, reviews,
      or meta-analyses. RESULTS: More than 10 classes of noninsulin treatments are
      available for T2DM. However, most treatments have been evaluated only in trials
      in patients aged <65 years, and trials in older populations are scarce.
      Therefore, health care providers should consider the overall benefit to risk,
      with a focus on risk factors in older patients. A1C reductions range from 0.6% to
      2%, with similar decreases observed for metformin, TZDs, sulfonylureas (SUs),
      glinides, and GLP-1 receptor agonists Treatment-associated adverse events vary.
      The prevalence of hypoglycemia is high with the secretagogues, SUs, and glinides
      (20% with glibenclamide or glipizide, 16% with repaglinide). The TZDs have been
      associated with an increased risk for heart failure (adjusted ratio = 1.60; 95%
      CI, 1.21-2.10; P < 0.001) compared with the other oral therapies.
      Gastrointestinal adverse events have been commonly reported with metformin (38%
      of patients), which is contraindicated in cases of renal insufficiency. Use of
      the GLP-1 RAs liraglutide and exenatide have been associated with comparable
      weight reductions of ~3 kg and with a low risk for hypoglycemia (prevalence, 4%
      with exenatide 10 MUg; ~5% with liraglutide 1.2 or 1.8 mg). Treatment with the
      GLP-1 RAs has been associated with transient gastrointestinal reactions, mainly
      nausea. CONCLUSIONS: The selection of noninsulin treatments in older patients
      with T2DM should be individualized based on patient assessment and on careful
      evaluation of the potential benefits (glycemic and extraglycemic) and risks (ie,
      hypoglycemia, weight gain, cardiovascular risks). More clinical trials in older
      patients, especially those aged >=65 years, with T2DM are needed.

PMID- 22136981
TI  - Concentration of biologically active polyamines in rabbit meat, liver and kidney
      after slaughter and their changes during meat storage and cooking.
AB  - The concentration of putrescine (PUT), spermidine (SPD) and spermine (SPM) was
      determined in chilled meat and kidneys of 18 rabbits and in liver of 12 animals
      24h after slaughter. Very low PUT concentrations were detected only in kidneys.
      Mean SPD levels were 2.2, 2.2, 61.7 and 32.7mgkg(-1) in saddle, leg, liver and
      kidneys, respectively. The respective SPM concentrations were 14.7, 8.0, 115 and
      88.4mgkg(-1). SPD and SPM losses of about one third of the initial levels were
      apparent in saddles stored at -18 degrees C for 8months. Losses of both
      polyamines of about 15-20% of the initial concentrations were found in saddles
      stored aerobically at +2 degrees C for up to 9days. Stewing of saddles caused
      significant SPD and SPM losses of about 20-25%, while upon roasting and pan
      roasting without oil a decrease of about 50% of the initial concentration was
      observed.

PMID- 22136980
TI  - Solving the antidepressant efficacy question: effect sizes in major depressive
      disorder.
AB  - BACKGROUND: Numerous reviews and meta-analyses of the antidepressant literature
      in major depressive disorders (MDD), both acute and maintenance, have been
      published, some claiming that antidepressants are mostly ineffective and others
      that they are mostly effective, in either acute or maintenance treatment.
      OBJECTIVE: The aims of this study were to review and critique the latest and most
      notable antidepressant MDD studies and to conduct our own reanalysis of the US
      Food and Drug Administration database studies specifically analyzed by Kirsch et
      al. METHODS: We gathered effect estimates of each MDD study. In our reanalysis of
      the acute depression studies, we corrected analyses for a statistical floor
      effect so that relative (instead of absolute) effect size differences were
      calculated. We also critiqued a recent meta-analysis of the maintenance treatment
      literature. RESULTS: Our reanalysis showed that antidepressant benefit is seen
      not only in severe depression but also in moderate depression and confirmed a
      lack of benefit for antidepressants over placebo in mild depression. Relative
      antidepressant versus placebo benefit increased linearly from 5% in mild
      depression to 12% in moderate depression to 16% in severe depression. The claim
      that antidepressants are completely ineffective, or even harmful, in maintenance
      treatment studies involves unawareness of the enriched design effect, which, in
      that analysis, was used to analyze placebo efficacy. The same problem exists for
      the standard interpretation of those studies, although they do not prove
      antidepressant efficacy either, since they are biased in favor of
      antidepressants. CONCLUSIONS: In sum, we conclude that antidepressants are
      effective in acute depressive episodes that are moderate to severe but are not
      effective in mild depression. Except for the mildest depressive episodes,
      correction for the statistical floor effect proves that antidepressants are
      effective acutely. These considerations only apply to acute depression, however.
      For maintenance, the long-term efficacy of antidepressants is unproven, but the
      data do not support the conclusion that they are harmful.

PMID- 22136982
TI  - Giant cystic superficial low-grade fibromyxoid sarcoma.
AB  - Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of fibrosarcoma
      characterized by combination of myxoid and fibrous zones consisted of bland
      spindled cells. Despite its innocuous histopathologic appearance, LGFMS can
      produce local recurrence and distant metastasis in the significant number of
      cases. Tumors are usually situated in deep soft tissues, whereas superficial
      localization in the dermis and subcutaneous fat is rare. We present a case of 56
      year-old man with the huge tumor on the lateral part of the right buttock that
      had been slowly enlarging over the previous 15 years. Needle aspiration cytology
      provided only serohemorrhagic fluid with the red blood cells and rare
      inflammatory elements. Complete surgical excision revealed subcutaneous tumor,
      measuring 220 * 180 * 130 mm, which was completely cystic, with the residual
      tumor tissue in the 3- to 25-mm-thick wall. Histopathologic, immunohistochemical,
      and cytogenetic analysis confirmed LGFMS diagnosis. Long evolution, large size,
      and the superficial location could cause the repetitive tissue damage and
      hemorrhage, eventually transforming the tumor into a large cystic mass. In some
      parts, collagen rosettes composed of eosinophilic core surrounded by a palisade
      of tumor cells could be seen, occasionally appearing to sprout from the
      perivascular fibrous coat. Data from the literature regarding cystic appearance
      as well as the superficial location and the size of LGFMS in relation to the
      clinical outcome are presented and discussed.

PMID- 22136983
TI  - A modified batch reactor system to study equilibrium-reactive transport problems.
AB  - It is difficult to design column experiments to study transport processes
      involving slow geochemical reactions that require long residence times to reach
      equilibrium. We propose a sequential equilibration reactor (SER) setup to study
      such equilibrium geochemical reactive transport problems. The proposed system
      consists of sequentially operated batch reactors that directly mimic typical one
      dimensional grids used in numerical reactive transport models. The SER
      experimental setup has the characteristics of batch experiments and provides
      complete control over the reaction time; in addition, the setup also includes
      certain simple transport features. We conducted several single-reactor and
      multiple-reactor SER experiments to investigate arsenic adsorption and transport
      on iron-oxide coated sand, at different pH, solid-solution ratio, and initial
      arsenic concentration conditions. The data generated from the experiments are
      compared against predictions from a geochemical transport code (PHREEQCI) that
      used previously developed surface complexation model parameters to describe the
      reaction system. The model predictions matched the SER experimental data well.
      The proposed SER system provides a flexible alternative to column experiments and
      allows better control over system parameters such as pH, reaction time, and solid
      solution ratio.

PMID- 22136984
TI  - New perspectives on nutritional interventions to augment lipid utilisation during
      exercise.
AB  - The enhancement of fat oxidation during exercise is an aim for both recreational
      exercising individuals and endurance athletes. Nutritional status may explain a
      large part of the variation in maximal rates of fat oxidation during exercise.
      This review reveals novel insights into nutritional manipulation of substrate
      selection during exercise, explaining putative mechanisms of action and
      evaluating the current evidence. Lowering the glycaemic index of the pre-exercise
      meal can enhance lipid utilisation by up to 100 % through reduced insulin
      concentrations, although its application may be restricted to specific training
      sessions rather than competition. Chronic effects of dietary glycaemic index are
      less clear and warrant future study before firm recommendations can be made. A
      flurry of recent advances has overthrown the conventional view of l-carnitine
      supplementation, with skeletal muscle uptake possible under certain dietary
      conditions and providing a strategy to influence energy metabolism in an exercise
      intensity-dependent manner. Use of non-carbohydrate nutrients to stimulate muscle
      l-carnitine uptake may prove more beneficial for optimising lipid utilisation,
      but this requires more research. Studies investigating fish oil supplementation
      on fat oxidation during exercise are conflicting. In spite of some strong
      putative mechanisms, the only crossover trial showed no significant effect on
      lipid use during exercise. Ca may increase NEFA availability although it is not
      clear whether these effects occur. Ca and caffeine can increase NEFA availability
      under certain circumstances which could theoretically enhance fat oxidation, yet
      strong experimental evidence for this effect during exercise is lacking. Co
      administration of nutrients to maximise their effectiveness needs further
      investigation.

PMID- 22136985
TI  - Brief report: a family risk study exploring bipolar spectrum problems and
      cognitive biases in adolescent children of bipolar parents.
AB  - Children of parents with bipolar disorder are at increased risk of bipolar
      spectrum diagnoses. This cross-sectional study explores cognitive factors in the
      prediction of vulnerability to bipolar disorder. Adolescents at high-risk (with a
      parent with bipolar disorder; n = 23) and age and gender matched adolescents (n =
      24) were recruited. Parent and adolescent diagnoses were evaluated (SCID and SADS
      L). Adolescents completed self-report measures assessing attributional style
      (ASQ), appraisal of hypomania-relevant experiences (HIQ), and hypomanic
      personality/temperament (HPS). Despite limitations in the power of the study,
      significantly more adolescents at high-risk for disorder received bipolar
      spectrum diagnoses. Groups did not differ in attributional style, hypomanic
      temperament or appraisals of hypomania-relevant experiences. A trend in ASQ
      results and general implications are discussed. The current study suggests that
      familial risk of bipolar disorder is not inevitably associated with cognitive
      biases in adolescence.

PMID- 22136986
TI  - Is chronic obstructive pulmonary disease associated with increased arterial
      stiffness?
AB  - OBJECTIVE: We hypothesize that airflow limitation is associated with increasing
      arterial stiffness and that having COPD increases a non-invasive measure of
      arterial stiffness - the aortic augmentation index (AIx) - independently of other
      CVD risk factors. METHODS: This population study is based on 3374 subjects from
      the Copenhagen City Heart Study; 494 had COPD. We used multiple linear regression
      analyses to examine the association between COPD and AIx adjusted for CVD risk
      factors. Furthermore, we analyzed the association between AIx and FEV(1), FVC and
      FEV(1)/FVC in the entire population. RESULTS: AIx was higher in subjects with
      COPD than in subjects without: 25.7 vs. 21.0 (p < 0.001) in men and 33.6 vs. 29.4
      (p < 0.001) in women. We found no increase in AIx with COPD adjusted for CVD risk
      factors: difference 0.63 (-0.26 to 1.52, p = 0.16). In sensitivity analyses in
      subjects younger than 60 years with exclusion of mild COPD from the analyses,
      COPD was associated with an increase in AIx in men only of 4.1 (0.88-7.22, p =
      0.007). AIx had a curvilinear association with FEV(1) and FVC but no association
      with the FEV(1)/FVC ratio. CONCLUSION: AIx and COPD are only weakly associated.
      In the general population, this finding argues against increased arterial
      stiffness, as measured by AIx, being a complication of COPD.

PMID- 22136987
TI  - Positive surgical margins after nephron-sparing surgery.
AB  - CONTEXT: Little is known on the natural history of positive surgical margins
      (PSMs) in partial nephrectomy (PN). Accumulating data suggest that secondary
      nephrectomy might not be necessary in all patients with PSMs after PN. OBJECTIVE:
      Provide an overview on incidence and risk factors for PSMs after partial
      nephrectomy and on the rate of local and distant disease recurrence related to
      PSMs. We also provide recommendations on how to avoid and how to treat PSMs after
      PN. EVIDENCE ACQUISITION: A nonsystematic literature research was based on
      Medline, Scopus, and Web of Science queries on these keywords: nephron-sparing
      surgery, partial nephrectomy/ies, and margin. Only human studies (original
      research) published in English were included. EVIDENCE SYNTHESIS: PSMs are
      present in 0-7% of patients after open PN, in 0.7-4% after laparoscopic PN, and
      in 3.9-5.7% after robot-assisted PN. The thickness of healthy parenchyma
      surrounding the tumour is irrelevant as long as complete tumour removal is
      achieved. The coincidence of a highly malignant tumour and PSM increases the risk
      of local recurrence. Intermediate follow-up data indicate that the vast majority
      of patients with PSMs will not experience local or distant tumour recurrence.
      Frozen-section analysis for evaluation of resection margins during PN is of minor
      clinical significance, as the surgeon's gross assessment of macroscopically
      negative margins provides reliable results. CONCLUSIONS: PSMs in PN are rare. As
      indicated by intermediate follow-up data, the majority of patients with PSMs
      after PN remain without disease recurrence, and a surveillance strategy seems
      preferable to surgical reintervention.

PMID- 22136988
TI  - Laparoendoscopic single-site surgery for the upper urinary tract: awaiting
      evidence.

PMID- 22136989
TI  - The importance of being 'well-placed': the influence of context on perceived
      typicality and esthetic appraisal of product appearance.
AB  - Earlier findings have suggested that esthetic appraisal of product appearances is
      influenced by perceived typicality. However, prior empirical research on
      typicality and esthetic appraisal of product appearances has not explicitly taken
      context effects into account. In this paper, we investigate how a specific
      context influences perceived typicality and thus the esthetic appraisal of
      product appearances by manipulating the degree of typicality of a product's
      appearance and its context. The findings of two studies demonstrate that the
      perceived typicality of a product appearance and consequently its esthetic
      appraisal vary depending on the typicality of the context in which the product is
      presented. Specifically, contrast effects occur for product appearances that are
      perceived as typical. Typical product appearances are perceived as more typical
      and are more esthetically appealing when presented in an atypical context
      compared to when presented in a typical context. No differences in perceived
      typicality and esthetic appraisal were found for product appearances that are
      perceived as atypical.

PMID- 22136990
TI  - Sporadic hemiplegic migraine presenting as acute encephalopathy.
AB  - A 10-year-old boy with psychomotor developmental delay and cerebellar vermis
      atrophy developed right hemiplegia with vomiting, unconsciousness, convulsions,
      and late-onset fever. Slow delta activity was noted over the left hemisphere on
      electroencephalography, and neuroimaging revealed swelling of the left temporo
      occipital cerebral cortex with restricted diffusivity, successive transient
      cortical atrophy, and hyperperfusion over the left cerebral hemisphere.
      Interleukin-6 was elevated in the cerebrospinal fluid. The acute symptoms
      resolved completely within 3 weeks after onset, but hypoperfusion persisted in
      the left posterior cortex thereafter. Another episode with transient left
      hemiplegia appeared 7 months later, followed by recurrence of migraine attacks.
      Analysis of the CACNA1A gene revealed a mutation of c.1997 C>T (p.T666M). None of
      his family members had migraine. This case represents an unusual evolution of
      sporadic hemiplegic migraine with manifestations of acute encephalopathy, for
      which the role of migraine-related inflammatory process is assumed.

PMID- 22136991
TI  - From heart to bad sleep-lessons for sleep apnoea in times of crisis.

PMID- 22136992
TI  - The demand for proof of quality.

PMID- 22136993
TI  - Ethical radiologic practice.

PMID- 22136994
TI  - Decision support for radiologist report recommendations.

PMID- 22136995
TI  - Quality and creativity.

PMID- 22136996
TI  - McAllen revisited.

PMID- 22136997
TI  - Introduction: Ain't misbehavin': ethical considerations in the research and
      practice of radiology.

PMID- 22136998
TI  - Toward providing effective, efficient, and equitable care: how much care can we
      afford?
AB  - There is no precise answer to the question of what is the "right amount" of
      imaging care. The author assesses the problem of what represents appropriate
      imaging care, the evidence base for using imaging, and the tension between the
      desires for imaging of individual patients and the health care needs of the
      broader society.

PMID- 22136999
TI  - Rationing and health care reform: not a question of if, but when.
AB  - Evidence-based medicine and rationing have been increasingly discussed in the
      context of health care reform recently. Both concepts are frequently the source
      of heated debate, leading to polarization of different health care practitioners
      and public parties. In some public arenas, rationing has become a dirty word. The
      term evidence-based medicine is perceived as being used as a "cover" for
      rationing. However, rationing is widespread, whether explicit or implicit, and
      exists within health care. Evidence-based medicine (or imaging) and rationing
      overlap considerably, and it looks like both are here to stay, given the current
      state of developed-world health care systems and the proposed reforms. The
      authors review these entities and argue that evidence-based medicine (or imaging)
      is one form of health care rationing. Rationing already occurs, and it is
      important that it be done in a way that provides the greater good for the
      majority. This article reviews the history of rationing and evidence-based
      medicine, the reasons evidence-based medicine and rationing are necessary,
      examples of rationing that already exist (economic), proposed forms of rationing
      (age based), the need for physicians (radiologists) to be at the forefront of any
      rationing efforts, and the basis (cost and comparative effectiveness research and
      evidence-based medicine) and principles of physician decision rationing (optimum
      outcome-based rationing) in the context of proposed health care reforms.

PMID- 22137000
TI  - Ethical considerations in CMS's coverage with evidence development.
AB  - This paper reviews the CMS coverage with evidence development policy, its manner
      of implementation, and key ethical issues raised by the policy. The author
      describes ethical considerations and issues associated with the process of
      coverage with evidence development for generating evidence for novel or emerging
      technologies.

PMID- 22137001
TI  - How to keep your integrity when performing sponsored (imaging) trials.
AB  - The broadening of imaging capabilities and the increasing capacity of imaging to
      quantitate biologic processes has increased industry interest in using imaging
      methods in new drug development. Investigators participating in industry
      sponsored trials should be aware of how such trials differ from investigator
      initiated, grant-funded research. In particular, investigators should be
      cognizant of possible ethical conflicts in the care of patients, the development
      and analysis of data, and issues related to the dissemination of results.

PMID- 22137002
TI  - Incidental findings in brain MRI research: what do we owe our subjects?
AB  - Concern regarding incidental findings on brain MRI studies has been increasing
      with the growing use of MRI as tool for scientific investigation. In this
      article, the authors provide an overview of possible approaches to address
      incidental findings. Incidental findings are surprisingly common (5%-20% of all
      examinations), although the percentage of clinically serious abnormalities is low
      (0.3%-3.4%). At present, there is no consensus concerning the optimal strategy on
      how to deal with incidental findings, in particular how to fulfill ethical
      responsibilities appropriately within the constraints of available resources.
      There are a variety of responses possible, and currently, reasonable guidelines
      exist for formulating a plan tailored to the needs of each institution that will
      meet the reasonable expectations of subjects participating in brain research
      studies.

PMID- 22137003
TI  - Handoffs between radiologists and patients: threat or opportunity?
AB  - Radiologists, referring physicians, and patients all have certain legal rights
      regarding access to medical records, including imaging data. The degree of
      patient access is likely to increase with the growing adoption of patient portals
      and personal health records. In addition, referring physicians and radiologists
      have a collective responsibility to ensure that important findings are
      transferred appropriately between their practices. In some cases when this is not
      possible, communicating directly with patients is the best way to protect the
      interests of both patients and radiologists. Even when not required, some
      radiologists have extensive experience communicating results directly to
      patients. Direct communication of radiology results to patients may present an
      opportunity to satisfy patients and reassert the importance of the physician
      patient relationship in radiology.

PMID- 22137004
TI  - Medical imaging data reconciliation, part 4: Reconciliation of radiology reports
      and clinical outcomes data.
AB  - An accurate clinical assessment of how radiology report data affect health care
      outcomes cannot be performed without the standardization, integration, and
      longitudinal analysis of radiology report and clinical outcomes data. The
      creation of such a technology can be accomplished by creating a standardized
      finding-specific radiology and clinical database, in which individual report
      findings are assigned extensible markup language tags and tracked over time with
      associated clinical data. The derived knowledge can in turn be used to improve
      overall outcomes through the data-derived analysis of reporting accuracy, imaging
      utilization, the timeliness of clinical care, and compliance with best practice
      guidelines.

PMID- 22137005
TI  - ACR Appropriateness Criteria(r) posttreatment follow-up of prostate cancer.
AB  - Although prostate cancer can be effectively treated, recurrent or residual
      disease after therapy is not uncommon and is usually detected by a rise in
      prostate-specific antigen. Patients with biochemical prostate-specific antigen
      relapse should undergo a prompt search for the presence of local recurrence or
      distant metastatic disease, each requiring different forms of therapy. Various
      imaging modalities and image-guided procedures may be used in the evaluation of
      these patients. Literature on the indications and usefulness of these radiologic
      studies and procedures in specific clinical settings is reviewed. 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- 22137006
TI  - Practical examples of natural language processing in radiology.

PMID- 22137007
TI  - Performance quality improvement projects: suggestions for radiologists who image
      children.

PMID- 22137008
TI  - Bismuth shields for CT dose reduction: do they help or hurt?

PMID- 22137009
TI  - Branding: an emerging necessity.

PMID- 22137010
TI  - Edward B. D. Neuhauser.

PMID- 22137011
TI  - Photoactive azoimine dyes: 4-(2-pyridylazo)-N,N-diethylaniline and 4-(2
      pyridylazo)-N,N-dimethylaniline: computational and experimental investigation.
AB  - 4-(2-Pyridylazo)-N,N-dimethylaniline and 4-(2-pyridylazo)-N,N-diethylaniline, two
      photoactive azoimine dyes, were prepared from the reaction of 2-aminopyridine
      with N,N-dialkyl-1,4-nitrosoaniline at room temperature. Structural
      characterizations of these dyes using single crystal X-ray diffraction, (1)H NMR,
      elemental analysis, mass spectroscopy and IR spectroscopy have been carried out.
      The X-ray structure indicates a trans configuration around the azo group. The
      photochemical behavior of these compounds differs from that of 2
      phenylazopyridine, the non-dialkylamino substituent compound. The synthesized
      compounds show emission spectra at room temperature while 2-phenylazopyridine
      does not. The excitation spectra of these compounds differ from their absorption
      spectra which can be explained on the basis of the trans to cis
      photoisomerization which is supported by the TD-PBE0/6-31G(d,p) calculations.
      Both oxidation of the dialkylamino substituents (-NR(2); R=-CH(3) and -C(2)H(5))
      and reduction of -N=N-/-N=N-(-) and -N=N-(-)/-N=N-(2-) were observed in the
      cyclic voltammogram indicating a pi-acidity of both dyes.

PMID- 22137012
TI  - Support vector regression and artificial neural network models for stability
      indicating analysis of mebeverine hydrochloride and sulpiride mixtures in
      pharmaceutical preparation: a comparative study.
AB  - A comparison between support vector regression (SVR) and Artificial Neural
      Networks (ANNs) multivariate regression methods is established showing the
      underlying algorithm for each and making a comparison between them to indicate
      the inherent advantages and limitations. In this paper we compare SVR to ANN with
      and without variable selection procedure (genetic algorithm (GA)). To project the
      comparison in a sensible way, the methods are used for the stability indicating
      quantitative analysis of mixtures of mebeverine hydrochloride and sulpiride in
      binary mixtures as a case study in presence of their reported impurities and
      degradation products (summing up to 6 components) in raw materials and
      pharmaceutical dosage form via handling the UV spectral data. For proper
      analysis, a 6 factor 5 level experimental design was established resulting in a
      training set of 25 mixtures containing different ratios of the interfering
      species. An independent test set consisting of 5 mixtures was used to validate
      the prediction ability of the suggested models. The proposed methods (linear SVR
      (without GA) and linear GA-ANN) were successfully applied to the analysis of
      pharmaceutical tablets containing mebeverine hydrochloride and sulpiride
      mixtures. The results manifest the problem of nonlinearity and how models like
      the SVR and ANN can handle it. The methods indicate the ability of the mentioned
      multivariate calibration models to deconvolute the highly overlapped UV spectra
      of the 6 components' mixtures, yet using cheap and easy to handle instruments
      like the UV spectrophotometer.

PMID- 22137013
TI  - Determination of dopamine at the nanogram level based on the formation of
      Prussian blue nanoparticles by resonance Rayleigh scattering technique.
AB  - In pH 2.6 HCl solution, dopamine (DA) could reduce Fe(III) to Fe(II), which
      further reacted with [Fe(CN)(6)](3-) to form a Fe(3)[Fe(CN)(6)](2) complex. By
      virtue of hydrophobic force and Van der Waals force, the complex aggregated to
      form Fe(3)[Fe(CN)(6)](2) nanoparticles with the average diameter of about 20 nm.
      This resulted in a significant enhancement of resonance Rayleigh scattering
      (RRS). The maximum wavelength of the ion-association complex was located at about
      350 nm. The increment of scattering intensity (DeltaI(RRS)) was directly
      proportional to the concentration of DA in the range of 0.06-1.0 MUg/mL. This
      method has high sensitivity and the detection limit (3sigma) for DA was 3.43
      ng/mL. In this work, the characteristics of absorption and RRS spectra of this
      reaction have been studied. The optimum reaction condition and influencing
      factors have been investigated. The method was applied to the determination of DA
      in pharmaceutical samples with satisfactory results. Furthermore, the reaction
      mechanism and the reasons of RRS enhancement have been explored.

PMID- 22137014
TI  - Optical and spectroscopic studies of potassium p-nitrophenolate dihydrate crystal
      for frequency doubling applications.
AB  - Non centrosymmetric potassium p-nitrophenolate dihydrate single crystals have
      been grown by employing the technique of slow solvent evaporation from aqueous
      solution by slightly adjusting the pH and growth temperature. The grown crystals
      have been identified from single crystal XRD analysis, FTIR and FT Raman
      spectroscopic techniques. The high resolution X-ray diffraction experiments
      substantiate good quality of the title material. Between 510 and 2000 nm, the
      material is observed to be nearly transparent allowing it to be explored for
      potential use in device fabrication. In addition, the photoluminescence spectrum
      of the grown crystal at room temperature shows a stable broad violet-blue
      emission around the 383-550 nm wavelengths with the maximum centered at 436 nm.
      Owing to its excellent non linear figure of merit and strong PL emission, the
      title crystal can have technological applications in opto-electronic devices.

PMID- 22137015
TI  - Response-repetition costs in task switching: how they are modulated by previous
      trial response-category activation.
AB  - A common finding is that there are response-repetition (RR) costs under task
      switching. Moreover, when the stimulus on the previous trial was congruent then
      RR costs are usually larger than when it was incongruent. This effect of the
      previous trial has been explained by assuming that a response category is
      generally inhibited after the execution of its corresponding response on the
      previous trial and that the amount of inhibition depends on the activation of the
      response category. However, up to now it was open which property of the response
      category activation on the previous trial is crucial: the absolute activation of
      the correct response category or the activation difference between the
      alternative response categories. To differentiate between these two possibilities
      we compared RR costs after congruent, neutral, and incongruent trials. In two
      experiments we found similar RR costs after congruent and neutral trials, whereas
      the RR costs were smaller after incongruent trials. These results support the
      hypothesis that the amount of response inhibition is determined by the activation
      differences between the alternative response categories on the previous trial.

PMID- 22137016
TI  - [Adolescent with anorexia nervosa: consequences on bone mineralization].
AB  - INTRODUCTION: Anorexia nervosa is responsible for abnormalities in bone
      mineralization, which are well known and described in adults, but less well
      documented in adolescents. The aim of this research was to evaluate the frequency
      and severity and to determine predictive factors for these abnormalities in a
      population of adolescents with diagnosed anorexia nervosa. PATIENTS AND METHODS:
      This retrospective study involved 39 female adolescents with anorexia nervosa
      having undergone dual energy X-ray absorptiometry prior to the age of 18 years.
      Clinical (age, Tanner puberty stages, weight, body mass index [BMI] at different
      times during the anorexia phase and amenorrhea features), radiological (bone
      mineral density [BMD] in Z-score units and in absolute values), and biological
      (calcemia and vitamin D) parameters were collected. RESULTS: In total, 20
      patients (51%) presented osteopenia (Z-score <-1 DS and >-2.5 DS) and 2 (5%) had
      osteoporosis (Z-score <-2.5 DS). Five (13%) exhibited a Z-score less than -2 DS.
      BMD expressed in Z-scores correlated with none of the parameters assessed. At
      univariate analysis, BMD in absolute values correlated with the age at disease
      onset, BMI, weight loss at the lowest weight achieved and BMI at the time of
      densitometry (P<0.01). At multivariate analyses, only the correlation with the
      age at disease onset persisted (P<0.05). CONCLUSION: Bone loss in anorexia
      nervosa is a complication that may be present as early as adolescence. It must be
      systematically searched for in all adolescents with severe malnutrition because,
      even if BMD correlated with nutritional parameters, no clinical predictor for
      osteoporosis or osteopenia could be identified in this study.

PMID- 22137017
TI  - Role of positron emission tomography in the early prediction of response to
      chemotherapy in patients with non--small-cell lung cancer.
AB  - In recent years, molecular imaging with [(18)F]fluorodeoxyglucose-positron
      emission tomography, [(18)F]FDG-PET, has become part of the standard of care in
      initial staging of patients with non-small-cell lung cancer. Currently, there is
      an increasing interest in the role of [(18)F]FDG-PET in the evaluation of
      biological characteristics of the tumor and the prediction of response to
      anticancer therapies at an early phase of treatment. According to the existing
      data, quantitative assessment of therapy-induced changes in tumor [(18)F]FDG
      uptake may allow the prediction of tumor response and patient outcome very early
      in the course of therapy. Treatment may be adjusted according to the
      chemosensitivity of the tumor tissue in an individual patient. Thus, [(18)F]FDG
      PET has the potential to reduce the side effects and costs of ineffective
      therapy. This review provides an update on recent studies that evaluate the role
      of [(18)F]FDG-PET in the early prediction of response to chemotherapy and
      prognosis in patients with non-small-cell lung cancer. In addition, it discusses
      the application of [(18)F]FDG-PET to the monitoring of new targeted forms of
      anticancer therapy and particularly of epidermal growth factor receptor tyrosine
      kinase inhibitors. Finally, it evaluates the usefulness of
      [(18)F]fluorothymidine, a PET tracer for imaging tumor proliferation, in
      predicting response to therapy in patients with lung cancer.

PMID- 22137018
TI  - GQ10 "Groundwater quality management in a rapidly changing world".

PMID- 22137019
TI  - Challenges in linear accelerator radiotherapy for chordomas and chondrosarcomas
      of the skull base: focus on complications.
AB  - PURPOSE: Intracranial chordomas and chondrosarcomas are histologically low-grade,
      locally invasive tumors that infiltrate the skull base. Currently, consensus
      therapy includes surgical resection and adjuvant radiotherapy. Radiation delivery
      is typically limited by the proximity of these tumors to critical skull base
      structures. METHODS: This is a retrospective review of 13 cases of chordomas and
      2 cases of chondroid chondrosarcomas of the skull based treated with linear
      accelerator stereotactic radiotherapy (SRT, n = 10) or stereotactic radiosurgery
      (SRS, n = 5). The average time to the most recent follow-up visit was 4.5 years.
      The tumor characteristics, treatment details, and outcomes were recorded. Each
      radiation plan was reviewed, and the dosage received by the brainstem, optic
      apparatus, and pituitary was calculated. RESULTS: Of the 10 patients treated with
      SRT, 6 were found to have unchanged or decreased tumor size as determined from
      radiographic follow-up. Of the 5 patients treated with SRS, 3 were found to have
      stable or unchanged tumors at follow-up. The complications included 1 SRT patient
      who developed endocrinopathy, 2 patients (1 treated with SRS and the other with
      SRT), who developed cranial neuropathy, and 1 SRS patient who developed visual
      deficits. Additionally, 1 patient who received both SRS and SRT within 2 years
      for recurrence experienced transient medial temporal lobe radiation changes that
      resolved. CONCLUSIONS: Where proton beam therapy is unavailable, linear
      accelerator-based SRT or radiosurgery remains a safe option for adjuvant therapy
      of chordomas and chondrosarcomas of the skull base. The exposure of the optic
      apparatus, pituitary stalk, and brainstem must be considered during planning to
      minimize complications. If the optic apparatus is included in the 80% isodose
      line, it might be best to fractionate therapy. Exposure of the pituitary stalk
      should be kept to <30 Gy to minimize endocrine dysfunction. Brainstem exposure
      should be limited to <60 Gy in fractions.

PMID- 22137021
TI  - Intensity-modulated radiation therapy with concurrent chemotherapy as
      preoperative treatment for localized gastric adenocarcinoma.
AB  - PURPOSE: The goal of this study was to evaluate dosimetric parameters, acute
      toxicity, pathologic response, and local control in patients treated with
      preoperative intensity-modulated radiation therapy (IMRT) and concurrent
      chemotherapy for localized gastric adenocarcinoma. METHODS: Between November 2007
      and April 2010, 25 patients with localized gastric adenocarcinoma were treated
      with induction chemotherapy, followed by preoperative IMRT and concurrent
      chemotherapy and, finally, surgical resection. The median radiation therapy dose
      was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18
      patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was
      performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and
      other surgeries in 5. RESULTS: Target coverage, expressed as the ratio of the
      minimum dose received by 99% of the planning target volume to the prescribed
      dose, was a median of 0.97 (range, 0.92-1.01). The median V(30) (percentage of
      volume receiving at least 30 Gy) for the liver was 26%; the median V(20)
      (percentage of volume receiving at least 20 Gy) for the right and left kidneys
      was 14% and 24%, respectively; and the median V(40) (percentage of volume
      receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed
      in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in
      5. Grade 4 acute toxicity did not develop in any patient. There were no
      significant differences in the rates of acute toxicity, hospitalization, or
      feeding tube use in comparison to those in a group of 50 patients treated with
      preoperative three-dimensional conformal radiation therapy with concurrent
      chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic
      complete response occurred in 5 (20%). CONCLUSIONS: Preoperative IMRT for gastric
      adenocarcinoma was well tolerated, accomplished excellent target coverage and
      normal structure sparing, and led to appropriate pathologic outcomes.

PMID- 22137020
TI  - Radioembolization for neuroendocrine liver metastases: safety, imaging, and long
      term outcomes.
AB  - PURPOSE: To present long-term outcomes on the safety and efficacy of Yttrium-90
      radioembolization in the treatment of unresectable hepatic neuroendocrine
      metastases refractory to standard-of-care therapy. METHODS AND MATERIALS: This
      study was approved by our institutional review board and was compliant with the
      Health Insurance Portability and Accountability Act. Forty patients with hepatic
      neuroendocrine metastases were treated with (90)Y radioembolization at a single
      center. Toxicity was assessed using National Cancer Institute Common Terminology
      Criteria v3.0. Response to therapy was assessed by World Health Organization
      (WHO) guidelines for size and European Association for the Study of the Liver
      disease (EASL) guidelines for necrosis. Time to response and overall survival
      were calculated using the Kaplan-Meier method. Univariate and multivariate
      analyses were performed. RESULTS: The median dose was 113 Gy (29-299 Gy).
      Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain
      (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin
      toxicities were experienced by 2 patients and 1 patient, respectively. Different
      responses were noted by WHO (complete response, 1.2%; partial response, 62.7%)
      and EASL (complete response, 20.5%; partial response, 43.4%). Median time to
      response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-,
      and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively.
      Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor
      burden <=25% (p = 0.0019), albumin >=3.5 g/dL (p = 0.017), and bilirubin <=1.2
      mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG
      performance score 0 and bilirubin <=1.2 mg/dL prognosticated better survival
      outcome on multivariate analysis (p = 0.0001 and p = 0.02). CONCLUSION: Yttrium
      90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor
      response and patient survival with low toxicity, in line with published national
      guidelines recommending radioembolization as a potential option for unresectable
      hepatic neuroendocrine metastases.

PMID- 22137022
TI  - Cosmetic outcomes and complications reported by patients having undergone breast
      conserving treatment.
AB  - PURPOSE: Over the past 30 years, much work in treatment of breast cancer has
      contributed to improvement of cosmetic and functional outcomes. The goal of
      breast-conservation treatment (BCT) is avoidance of mastectomy through use of
      lumpectomy and adjuvant radiation. Modern data demonstrate "excellent" or "good"
      cosmesis in >90% of patients treated with BCT. METHODS AND MATERIALS: Patient
      reported data were gathered via a convenience sample frame from breast cancer
      survivors using a publically available, free, Internet-based tool for creation of
      survivorship care plans. During use of the tool, breast cancer survivors are
      queried as to the cosmetic appearance of the treated breast, as well as perceived
      late effects. All data have been maintained anonymously with internal review
      board approval. RESULTS: Three hundred fifty-four breast cancer survivors having
      undergone BCT and voluntarily using this tool were queried with regard to breast
      cosmesis and perceived late effects. Median diagnosis age was 48 years, and
      median current age 52 years. "Excellent" cosmesis was reported by 27% (n = 88),
      "Good" by 44% (n = 144), "Fair" by 24% (n = 81), and "Poor" by 5% (n = 18). Of
      the queries posted to survivors after BCT, late effects most commonly reported
      were cognitive changes (62%); sexual concerns (52%); changes in texture and color
      of irradiated skin (48%); chronic pain, numbness, or tingling (35%); and loss of
      flexibility in the irradiated area (30%). Survivors also described
      osteopenia/osteoporosis (35%), cardiopulmonary problems (12%), and lymphedema
      (19%). CONCLUSIONS: This anonymous tool uses a convenience sample frame to gather
      patient reported assessments of cosmesis and complications after breast cancer.
      Among the BCT population, cosmetic assessment by survivors appears less likely to
      be "excellent" or "good" than would be expected, with 30% of BCT survivors
      reporting "fair" or "poor" cosmesis. Patient reported incidence of chronic pain,
      as well as cognitive and sexual changes, also appears higher than expected.

PMID- 22137023
TI  - Long-term outcome after radiotherapy in patients with atypical and malignant
      meningiomas--clinical results in 85 patients treated in a single institution
      leading to optimized guidelines for early radiation therapy.
AB  - PURPOSE: Previously, we could show that the new World Health Organization (WHO)
      classification of meningiomas significantly correlated with outcome in patients
      with atypical and anaplastic histology. In the present work, we analyzed our long
      term experience in radiotherapy for atypical and malignant meningioma diagnosed
      according to the most recent WHO categorization system. PATIENTS AND METHODS:
      Sixty-two patients with atypical and 23 patients with malignant meningioma have
      been treated with radiotherapy. Sixty percent of all patients received
      radiotherapy (RT) after surgical resection, 19% at disease progression and 8.3%
      as a primary treatment. Radiation was applied using different techniques
      including fractionated stereotactic RT (FSRT), intensity-modulated RT, and
      combination treatment with carbon ions. The median PTV was 156.0 mL. An average
      dose of 57.6 Gy (range, 30-68.4 Gy) in 1.8-3 Gy fractions was applied. All
      patients were followed regularly including clinical-neurological follow-up as
      well as computed tomographies or magnetic resonance imaging. RESULTS: Overall
      survival was impacted significantly by histological grade, with 81% and 53% at 5
      years for atypical or anaplastic meningiomas, respectively. This difference was
      significant at p = 0.022. Eighteen patients died of tumor progression during
      follow-up. Progression-free survival was 95% and 50% for atypical, and 63% and
      13% for anaplastic histology at 2 and 5 years. This difference was significant at
      p = 0.017. Despite histology, we could not observe any prognostic factors
      including age, resection status, or Karnofsky performance score. However,
      preexisting clinical symptoms observed in 63 patients improved in 29.3% of these
      patients. CONCLUSION: RT resulted in improvement of preexisting clinical
      symptoms; outcome is comparable to other series reported in the literature. RT
      should be offered after surgical resection after initial diagnosis to increase
      progression-free survival as well as overall survival. Novel clinical concepts
      are under investigation to further improve outcome in patients with high-grade
      meningiomas.

PMID- 22137024
TI  - Dose-effect relationships for individual pelvic floor muscles and anorectal
      complaints after prostate radiotherapy.
AB  - PURPOSE: To delineate the individual pelvic floor muscles considered to be
      involved in anorectal toxicity and to investigate dose-effect relationships for
      fecal incontinence-related complaints after prostate radiotherapy (RT). METHODS
      AND MATERIALS: In 48 patients treated for localized prostate cancer, the internal
      anal sphincter (IAS) muscle, the external anal sphincter (EAS) muscle, the
      puborectalis muscle (PRM), and the levator ani muscles (LAM) in addition to the
      anal wall (Awall) and rectal wall (Rwall) were retrospectively delineated on
      planning computed tomography scans. Dose parameters were obtained and compared
      between patients with and without fecal urgency, incontinence, and frequency.
      Dose-effect curves were constructed. Finally, the effect of an endorectal
      balloon, which was applied in 28 patients, was investigated. RESULTS: The total
      volume of the pelvic floor muscles together was about three times that of the
      Awall. The PRM was exposed to the highest RT dose, whereas the EAS received the
      lowest dose. Several anal and rectal dose parameters, as well as doses to all
      separate pelvic floor muscles, were associated with urgency, while incontinence
      was associated mainly with doses to the EAS and PRM. Based on the dose-effect
      curves, the following constraints regarding mean doses could be deduced to reduce
      the risk of urgency: <= 30 Gy to the IAS; <= 10 Gy to the EAS; <= 50 Gy to the
      PRM; and <= 40 Gy to the LAM. No dose-effect relationships for frequency were
      observed. Patients treated with an endorectal balloon reported significantly less
      urgency and incontinence, while their treatment plans showed significantly lower
      doses to the Awall, Rwall, and all pelvic floor muscles. CONCLUSIONS:
      Incontinence-related complaints show specific dose-effect relationships to
      individual pelvic floor muscles. Dose constraints for each muscle can be
      identified for RT planning. When only the Awall is delineated, substantial
      components of the continence apparatus are excluded.

PMID- 22137025
TI  - Predictors of metastatic disease after prostate brachytherapy.
AB  - PURPOSE: To identify predictors of metastatic disease after brachytherapy
      treatment for prostate cancer. METHODS AND MATERIALS: All patients who received
      either brachytherapy alone (implant) or brachytherapy in combination with
      external beam radiation therapy for treatment of localized prostate cancer at The
      Mount Sinai Hospital between June 1990 and March 2007 with a minimum follow-up of
      2 years were included. Univariate and multivariable analyses were performed on
      the following variables: risk group, Gleason score (GS), clinical T stage,
      pretreatment prostate-specific antigen level, post-treatment prostate-specific
      antigen doubling time (PSA-DT), treatment type (implant vs. implant plus external
      beam radiation therapy), treatment era, total biological effective dose, use of
      androgen deprivation therapy, age at diagnosis, and race. PSA-DT was analyzed in
      the following ordinate groups: 0 to 90 days, 91 to 180 days, 180 to 360 days, and
      greater than 360 days. RESULTS: We included 1,887 patients in this study.
      Metastases developed in 47 of these patients. The 10-year freedom from distant
      metastasis (FFDM) rate for the entire population was 95.1%. Median follow-up was
      6 years (range, 2-15 years). The only two significant predictors of metastatic
      disease by multivariable analyses were GS and PSA-DT (p < 0.001 for both
      variables). Estimated 10-year FFDM rates for GS of 6 or less, GS of 7, and GS of
      8 or greater were 97.9%, 94.3%, and 76.1%, respectively (p < 0.001). Estimated
      FFDM rates for PSA-DT of 0 to 90 days, 91 to 180 days, 181 to 360 days, and
      greater than 360 days were 17.5%, 67.9%, 74%, and 94.8%, respectively (p <
      0.001). Estimated 10-year FFDM rates for the low-, intermediate-, and high-risk
      groups were 98.6%, 96.2%, and 86.7%, respectively. A demographic shift to
      patients presenting with higher-grade disease in more recent years was observed.
      CONCLUSIONS: GS and post-treatment PSA-DT are both statistically significant
      independent predictors of metastatic disease. Patients with a high GS and/or
      short PSA-DT have a higher likelihood of developing metastatic disease and should
      be considered for systemic therapy.

PMID- 22137026
TI  - A planned neck dissection is not necessary in all patients with N2-3 head-and
      neck cancer after sequential chemoradiotherapy.
AB  - PURPOSE: To assess the role of a planned neck dissection (PND) after sequential
      chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal
      disease. METHODS AND MATERIALS: We reviewed 90 patients with N2-N3 head-and-neck
      squamous cell carcinoma treated between 1991 and 2001 on two sequential
      chemoradiotherapy protocols. All patients received induction and concurrent
      chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine.
      Patients with less than a clinical complete response (cCR) in the neck proceeded
      to a PND after chemoradiation. The primary endpoint was nodal response. Clinical
      outcomes and patterns of failure were analyzed. RESULTS: The median follow-up
      durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and
      5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal
      cCR whose necks were observed, 5 patients had neck failures as a component of
      their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1);
      neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited
      only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n =
      1)]. The pathologic complete response (pCR) rate for those with a clinical
      partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control
      rates after cCR, cPR->pCR, and cPR->pPR were 90%, 93%, and 78%, respectively (p =
      0.36). The 5-year disease-free survival rates for the cCR, cPR->pCR, and cPR->pPR
      groups were 53%, 75%, and 42%, respectively (p = 0.04). CONCLUSION: In our
      series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would
      have benefited only 4% and, therefore, is not recommended. Patients with a cPR
      should be treated with PND. Residual tumor in the PND specimens was associated
      with poor outcomes; therefore, aggressive therapy is recommended. Studies using
      novel imaging modalities are needed to better assess treatment response.

PMID- 22137027
TI  - Complement factor H-ligand interactions: self-association, multivalency and
      dissociation constants.
AB  - Factor H (FH) is the major plasma regulator of the central complement protein C3b
      in the alternative pathway of complement activation. The elucidation of the FH
      interactions with five major ligands (below) is complicated by their weak MUM
      dissociation constants K(D) and FH multivalency. We present the first survey of
      all the K(D) values for the major FH-ligand interactions and critically review
      their physiological significance. (i) FH self-association is presently well
      established. We review multiple data sets that show that 5-14% of FH is self
      associated in physiological conditions. FH self-association is significant for
      both laboratory investigations and physiological function.(ii) The FH-C3b complex
      shows low M affinity, meaning that the complex is not fully formed in plasma. In
      addition, C3, its hydrolysed form C3u, and its cleaved forms C3b and C3d show
      multimerisation. Current data favour a model when two C3b molecules bind
      independently to one FH molecule, as opposed to a1:1 stoichiometry where FH wraps
      itself around C3b.(iii) Heparin is often used as an analogue of the polyanionic
      host cell surface. The FH-heparin complex also shows a low M affinity, again
      meaning that complexes are not fully formed in vivo. The oligomeric FH-heparin
      complexes clarify a two-site interaction model of FH with host-cell surfaces.(iv)
      Reinvestigation of the FH and C-reactive protein (CRP) interaction revealed that
      this can only occur in plasma when CRP levels are elevated during acute-phase
      conditions. Given that CRP binds more weakly to the His402 allotype of FH than
      the Tyr402 allotype, this suggested a link with age-related macular degeneration
      (AMD).(v) FH activity is inhibited by zinc, which causes FH to aggregate
      strongly. High levels of bioavailable zinc occur in sub-retinal pigment
      epithelial deposits which lead to AMD. Excess zinc binds weakly to a central
      region of FH, explaining how zinc inhibits FH regulation of C3b.

PMID- 22137028
TI  - Increased serum human beta-defensin-2 levels in atopic dermatitis: relationship
      to IL-22 and oncostatin M.
AB  - Atopic dermatitis (AD) is associated with dysregulated expression of human beta
      defensins (hBDs) and infiltration of T cells producing cytokines which regulate
      hBD expression. We examined serum levels of hBDs and cytokines in AD patients,
      the effects of cytokines on hBD production in human keratinocytes, and those of
      hBDs on cytokine production in human peripheral blood-derived T cells. Levels of
      serum hBD-2, IL-22, and oncostatin M, but not hBD-3, were higher in AD patients
      than in normal donors. Serum hBD-2 levels of AD patients correlated with AD
      scoring and IL-22 levels. IL-22 and oncostatin M enhanced hBD-2 production and
      signal transducer and activator of transcription 3 (STAT3) activities strongly
      and hBD-3 production moderately in human keratinocytes. STAT3 inhibitor
      suppressed IL-22 and oncostatin M-induced production of hBD-2 and hBD-3. hBD-2
      strongly and hBD-3 moderately enhanced IL-22 and oncostatin M production, whereas
      hBD-3 strongly and hBD-2 moderately enhanced IL-31, IL-13, and IL-4 production in
      CD3/28-stimulated T cells. hBD-2 induced phosphorylation of c-Jun N-terminal
      kinase, extracellular signal-regulated kinase, and Akt, while hBD-3 induced
      phosphorylation of inhibitory kappaB kinase, p38 mitogen-activated protein
      kinase, and Akt in CD3/28-stimulated T cells. Inhibitors of these signals
      attenuated hBD-2- or hBD-3-induced production of cytokines. These results suggest
      that serum hBD-2 may be a biomarker of skin inflammation. IL-22 and oncostatin M
      may enhance hBD-2 production via STAT3 in keratinocytes, while hBD-2 may enhance
      IL-22 and oncostatin M production in T cells. hBD-3 may enhance T(H)2 responses.

PMID- 22137029
TI  - A cholesterol and actinide dependent shadow biosphere of archaea and viroids in
      autoimmune diseases.
AB  - Endogenous digoxin has been related to the pathogenesis of multiple sclerosis and
      other autoimmune diseases like systemic lupus erythematosis and rheumatoid
      arthritis. The possibility of endogenous digoxin synthesis by archaea with a
      mevalonate pathway and cholesterol catabolism was considered. 10 cases each of
      multiple sclerosis and other autoimmune diseases like systemic lupus
      erythematosis and rheumatoid arthritis before starting treatment and 10 age and
      sex matched healthy controls from general population were chosen for the study.
      Cholesterol substrate was added to the plasma of the patients and the generation
      of cytochrome F420, free RNA, free DNA, polycyclic aromatic hydrocarbon, hydrogen
      peroxide, serotonin, pyruvate, ammonia, glutamate, cytochrome C, hexokinase, ATP
      synthase, HMG CoA reductase, digoxin and bile acids were studied. The changes
      with the addition of antibiotics and cerium to the patient's plasma were also
      studied. The statistical analysis was done by ANOVA. The parameters mentioned
      above were increased the patient's plasma with addition of cholesterol substrate.
      The addition of antibiotics to the patient's plasma caused a decrease in all the
      parameters while addition of cerium increased their levels. An actinide dependent
      shadow biosphere of archaea and viroids is described in multiple sclerosis and
      other autoimmune diseases like systemic lupus erythematosis and rheumatoid
      arthritis contributing to their pathogenesis.

PMID- 22137031
TI  - Binding of TNT to amplifying fluorescent polymers: an ab initio and molecular
      dynamics study.
AB  - Molecular modeling techniques were employed to study the interaction of
      trinitrotoluene with an amplifying fluorescent polymer used in explosive sensor
      devices. The pentiptycene moiety present in these polymers appears to be the most
      energetically favorable binding site for trinitrotoluene. Surface features of the
      polymer suggest that the small cavity feature of the pentiptycene moiety may be
      more available for binding to analyte compounds due to steric crowding about the
      large cavity. Binding energies between model binding sites of the polymer and
      various analyte compounds were more rigorously estimated by semiempirical and ab
      initio techniques. Binding energies were found to be largest with trinitrotoluene
      and other nitroaromatic compounds. Electrostatic and pi-stacking interactions
      between trinitrotoluene and the model host were investigated by studying a series
      of modified host compounds.

PMID- 22137030
TI  - Prevention of liver ischemia reperfusion injury by a combined thyroid hormone and
      fish oil protocol.
AB  - Several preconditioning strategies are used to prevent ischemia-reperfusion (IR)
      liver injury, a deleterious condition associated with tissue resection,
      transplantation or trauma. Although thyroid hormone (T3) administration exerts
      significant protection against liver IR injury in the rat, its clinical
      application is controversial due to possible adverse effects. Considering that
      prevention of liver IR injury has also been achieved by n-3 polyunsaturated fatty
      acid (n-3 PUFA) supplementation to rats, we studied the effect of n-3 PUFA
      dietary supplementation plus a lower dose of T3 against IR injury. Male Sprague
      Dawley rats receiving fish oil (300 mg/kg) for 3 days followed by a single
      intraperitoneal dose of 0.05 mg T3/kg were subjected to 1 h of ischemia followed
      by 20 h of reperfusion. Parameters of liver injury (serum transaminases,
      histology) and oxidative stress (liver contents of GSH and oxidized proteins)
      were correlated with fatty acid composition, NF-kappaB activity, and tumor
      necrosis factor-alpha (TNF-alpha) and haptoglobin expression. IR significantly
      modified liver histology; enhanced serum transaminases, TNF-alpha response or
      liver oxidative stress; and decreased liver NF-kappaB activity and haptoglobin
      expression. Although IR injury was not prevented by either n-3 PUFA
      supplementation or T3 administration, substantial decrease in liver injury and
      oxidative stress was achieved by the combined protocol, which also led to
      increased liver n-3 PUFA content and decreased n-6/n-3 PUFA ratios, with recovery
      of NF-kappaB activity and TNF-alpha and haptoglobin expression. Prevention of
      liver IR injury achieved by a combined protocol of T3 and n-3 PUFA
      supplementation may represent a novel noninvasive preconditioning strategy with
      potential clinical application.

PMID- 22137032
TI  - Musculoskeletal phenotype through the life course: the role of nutrition.
AB  - This review considers the definition of a healthy bone phenotype through the life
      course and the modulating effects of muscle function and nutrition. In
      particular, it will emphasise that optimal bone strength (and how that is
      regulated) is more important than simple measures of bone mass. The forces
      imposed on bone by muscle loading are the primary determinants of musculoskeletal
      health. Any factor that changes muscle loading on the bone, or the response of
      bone to loading results in alterations of bone strength. Advances in technology
      have enhanced the understanding of a healthy bone phenotype in different skeletal
      compartments. Multiple components of muscle strength can also be quantified. The
      critical evaluation of emerging technologies for assessment of bone and muscle
      phenotype is vital. Populations with low and moderate/high daily Ca intakes
      and/or different vitamin D status illustrate the importance of nutrition in
      determining musculoskeletal phenotype. Changes in mass and architecture maintain
      strength despite low Ca intake or vitamin D status. There is a complex
      interaction between body fat and bone which, in addition to protein intake, is
      emerging as a key area of research. Muscle and bone should be considered as an
      integrative unit; the role of body fat requires definition. There remains a lack
      of longitudinal evidence to understand how nutrition and lifestyle define
      musculoskeletal health. In conclusion, a life-course approach is required to
      understand the definition of healthy skeletal phenotype in different populations
      and at different stages of life.

PMID- 22137033
TI  - Profound pectus excavatum in Marfan's syndrome.

PMID- 22137034
TI  - Of colors and teeth.

PMID- 22137035
TI  - Perspectives November 2011.

PMID- 22137036
TI  - Biosynthesis of non-cellulosic polysaccharides of plant cell walls.
AB  - Enzymes that make the polymer backbones of plant cell wall polysaccharides have
      proven to be recalcitrant to biochemical purification. Availability of mutational
      genetics and genomic tools paved the way for rapid progress in identifying genes
      encoding various cell wall glycan synthases. Mutational genetics, the primary
      tool used in unraveling cellulose biosynthesis, was ineffective in assigning
      function to any of the hemicellulosic, polymerizing glycan synthases. A
      combination of comparative genomics and functional expression in a heterologous
      system allowed identification of various cellulose synthase-like (Csl) sequences
      as being involved in the formation of beta-1,4-mannan, beta-1,4-glucan, and mixed
      linked glucan. A number of xylose-deficient mutants have led to a variety of
      genes, none of which thus far possesses the motifs known to be conserved among
      polymerizing beta-glycan synthases. Except for xylan synthase, which appears to
      be an agglomerate of proteins just like cellulose synthase, Golgi glycan
      synthases already identified suggest that the catalytic polypeptide by itself is
      sufficient for enzyme activity, most likely as a homodimer. Several of the Csl
      genes remain to be assigned a function. The possibility of the involvement of
      various Csl genes in making more than one product remains.

PMID- 22137037
TI  - Secondary metabolites from Spirotropis longifolia (DC) Baill and their antifungal
      activity against human pathogenic fungi.
AB  - A phytochemical study of the ethyl acetate extract of the roots and adventitious
      roots of Spirotropis longifolia, a monodominant tree species of the Guianan
      rainforest, has allowed the isolation of three compounds: 2-hydroxy-8,9
      methylenedioxy-2',2'-dimethylpyrano-[5',6':4,3]-6a-prenyl-[6aS,11aS]-pterocarpan
      (spirotropin A), 2-hydroxy-8,9-methylenedioxy-2',2'-dimethyl-3',4'-dihydropyrano
      [5',6':4,3]-6a-prenyl-[6aS,11aS]-pterocarpan (spirotropin B), and 5,7-dihydroxy
      6,8-diprenyl-2'''',2''''-dimethylpyrano[5'''',6'''': 3',4']-isoflavone
      (spirotropone). In addition, 10 known compounds, trans-oxyresveratrol, trans
      resveratrol, piceatannol, daidzein, genistein, isoprunetin, lupeol, latifolol,
      gnetin D and gnetin E, were also isolated. These compounds were evaluated for
      their antifungal activity and their cytotoxicity, and their structures were
      established by 1D and 2D NMR, HRMS, CD and optical rotation measurements.

PMID- 22137038
TI  - [Invasive aspergillosis: new tools for a targeted medical management].

PMID- 22137039
TI  - Causes of blindness and visual impairment in Latin America.
AB  - We review what is known in each country of the Latin American region with regards
      to blindness and visual impairment and make some comparisons to Hispanic
      populations in the United States. Prevalence of blindness varied from 1.1% in
      Argentina to 4.1% in Guatemala in people 50 years of age and older, with the
      major cause being cataract. Diabetic retinopathy and glaucoma are starting to
      make serious inroads, although epidemiological data are limited, and age-related
      macular degeneration is now a concern in some populations. Infectious diseases
      such as trachoma and onchocerciasis are quickly diminishing. Although progress
      has been made, retinopathy of prematurity remains the major cause of childhood
      blindness. If VISION 2020 is to succeed, many more epidemiological studies will
      be needed to set priorities, although some can be of the Rapid Assessment of
      Avoidable Blindness design. Developing the infrastructure for screening and
      treatment of ophthalmic disease in Latin America continues to be a challenge.

PMID- 22137040
TI  - Use of poly(ether-block-amide) in pervaporation coupling with a fermentor to
      enhance butanol production in the cultivation of Clostridium acetobutylicum.
AB  - The toxicity of the end-products of acetone-butanol-ethanol (ABE) process, mainly
      butanol, is recognized as the major problem contributing to the low productivity
      of butanol. The pervaporation technique was regarded as one of the ways to
      efficiently remove organic components. The results of pervaporation performance
      of poly(ether-block-amide) (PEBA) and polydimethylsiloxane (PDMS) membrane in a
      model solution indicated that PEBA membrane owned a higher butanol permeation
      flux of 9.975 gm(-2)h(-1) as opposed to 3.911 gm(-2)h(-1) using a PDMS membrane.
      Moreover, a higher temperature would result in a higher permeation flux, but has
      a lower separation factor (alpha) obtained, while using PEBA membrane. The batch
      fermentor operation connected to the pervaporation with PEBA membrane created 43%
      and 34% of increase in the butanol productivity and in the yield as compared to
      that of the simple batch. The fed-batch fermentation mode by glucose feeding
      combined with PEBA pervaporation lasting for 24h could achieve 39% increase of
      butanol productivity as compared to a simple batch. Conclusively, the
      pervaporation with PEBA membrane coupling with fermentor was presumed to be
      capable of enhancing butanol production in ABE fermentation, which might have the
      potential applied in the commercialized ABE fermentation process.

PMID- 22137041
TI  - Fibrinolytic enzyme from newly isolated marine bacterium Bacillus subtilis ICTF
      1: media optimization, purification and characterization.
AB  - Fibrinolytic enzymes are important in treatment of cardiovascular diseases. The
      present work reports isolation, screening and identification of marine cultures
      for production of fibrinolytic enzymes. A potent fibrinolytic enzyme-producing
      bacterium was isolated from marine niches and identified as Bacillus subtilis
      ICTF-1 on the basis of the 16S rRNA gene sequencing and biochemical properties.
      Further, media optimization using L(18)-orthogonal array method resulted in
      enhanced production of fibrinolytic enzyme (8814 U/mL) which was 2.6 fold higher
      than in unoptimized medium (3420 U/mL). In vitro assays revealed that the enzyme
      could catalyze blood clot lysis effectively, indicating that this enzyme could be
      a useful thrombolytic agent. A fibrinolytic enzyme was purified from the culture
      supernatant to homogeneity by three step procedures with a 34.42-fold increase in
      specific activity and 7.5% recovery. This purified fibrinolytic enzyme had
      molecular mass of 28 kDa, optimal temperature and pH at 50  degrees C and 9,
      respectively. It was stable at pH 5.0-11.0 and temperature of 25-37  degrees C.
      The enzyme activity was activated by Ca(2+) and obviously inhibited by Zn(2+),
      Fe(3)(+), Hg(2+) and PMSF. The purified fibrinolytic enzyme showed high stability
      towards various surfactants and was relatively stable towards oxidizing agent.
      Considering these properties purified fibrinolytic enzyme also finds potential
      application in laundry detergents in addition to thrombolytic agent. The gene
      encoding fibrinolytic enzyme was isolated and its DNA sequence was determined.
      Compared the full DNA sequence with those in NCBI, it was considered to be a
      subtilisin like serine-protease.

PMID- 22137042
TI  - Fluorescein angiographic findings after intra-arterial chemotherapy for
      retinoblastoma.
AB  - PURPOSE: To evaluate fluorescein angiography (FA) findings after intra-arterial
      chemotherapy (IAC) for retinoblastoma. DESIGN: Retrospective case series.
      PARTICIPANTS: Twenty-four eyes of 24 patients. INTERVENTION: Fifty-five IAC
      procedures for delivery of melphalan 5 mg and possible carboplatin 30 mg. MAIN
      OUTCOME MEASURES: Vascular flow of iris, retina, and choroid after IAC. RESULTS:
      All patients received melphalan 5 mg, whereas the first 6 patients also were
      treated with additional carboplatin 30 mg. The IAC was performed as primary
      treatment in 17 eyes and as secondary treatment (after systemic chemotherapy) in
      7 eyes. Two patients also received external-beam radiotherapy before IAC. At
      presentation, FA revealed neovascularization of the iris (NVI) in 8 eyes, and
      after IAC, complete NVI regression was noted in 5 eyes (63%). After a mean follow
      up of 13 months after IAC, FA depicted the main tumor with decreased fluorescence
      in 22 eyes (92%). After 55 ophthalmic artery catheterizations, retinal vascular
      abnormalities by FA were detected in 7 eyes (13%) and choroidal vascular
      abnormalities were detected in 6 eyes (11%). The retinal abnormalities included
      ophthalmic artery obstruction (n = 1), transient ophthalmic artery spasm (n = 1),
      central retinal artery obstruction (n = 1), branch retinal artery obstruction (n
      = 2), and peripheral retinal ischemia (n = 2). Additional retinal
      neovascularization was found in 1 patient. The choroidal abnormalities included
      sector (n = 5) or diffuse (n = 1) choroidal nonperfusion. New-onset iris
      neovascularization was found in 2 patients. Retinal vascular abnormalities were
      diagnosed after median of 1 month after the first IAC, whereas choroidal vascular
      abnormalities were found after median of 5 months after the first IAC.
      CONCLUSIONS: Fluorescein angiography suggests that vascular perfusion to the
      retina and the choroid can be compromised after IAC for retinoblastoma. The most
      common vascular abnormality was choroidal sector or diffuse nonperfusion.

PMID- 22137044
TI  - Ethical considerations of biomarker use in neurodegenerative diseases--a case
      study of Alzheimer's disease.
AB  - A major issue in current Alzheimer research presents in a growing dysbalance
      between a swiftly advancing biological marker and diagnostic research field
      (including advances in genetic research towards genetic profiling), key aspects
      of which have already found their way into newly proposed diagnostic criteria and
      international clinical dementia guidelines, and still rather limited and
      stagnating therapeutic and preventive options for physicians and patients
      worldwide. While Alzheimer's disease (AD) to date can be diagnosed with high
      accuracy years ahead of the late stage clinical syndromal dementia manifestation
      supported by biomarker guided detection of AD-characteristic pathophysiological
      features, there are currently no approved preventive or disease-modifying
      therapies available and the existing approved symptomatic therapy options provide
      only modest effect sizes in already demented patients without affecting the
      overall course and progression of the chronically progressive and complex brain
      disease. This unsatisfactory situation brings along a number of important ethical
      issues that need to be addressed. We outline some of the relevant ethical
      implications mainly related to the patient's best interest as well as to the
      patient's autonomy in the specific context of medical, psychological and social
      consequences of predicting AD using multi-modal biological markers. Consent,
      disclosure, or failure to disclose, information from genetic and predictive
      biomarker results raises significant ethical concerns among IRBs, regulators and
      advocacy groups. With the swift advances in ever earlier detection, diagnosis and
      classification in AD, a worldwide debate on ethical issues and consensus
      processes to reach a common ethical framework is warranted to safely and
      responsibly bring the best possible diagnostic measures as early as possible to
      patients and to the health care system.

PMID- 22137043
TI  - Glaucoma Progression Analysis software compared with expert consensus opinion in
      the detection of visual field progression in glaucoma.
AB  - PURPOSE: To compare the results of Glaucoma Progression Analysis (GPA, Carl Zeiss
      Meditec, Dublin, CA) to subjective expert consensus in the detection of
      glaucomatous visual field progression. DESIGN: Retrospective, observational case
      series. PARTICIPANTS: We included 100 eyes of 83 glaucoma patients. METHODS: Five
      serial Humphrey visual fields from 100 eyes of 83 glaucoma patients were
      evaluated by 5 masked glaucoma subspecialists for determination of progression.
      Four months later, with a randomly reordered patient sequence, the same visual
      field series were reevaluated by the same graders, at which time they had access
      to the Glaucoma Progression Analysis (GPA) printout. MAIN OUTCOME MEASURES: The
      level of agreement between majority expert consensus and GPA, both before and
      after access to GPA data, was assessed using kappa statistics. RESULTS: On
      initial review and on reevaluation with access to the GPA printout, the level of
      agreement between majority expert consensus and GPA was fair (kappa = 0.52, 95%
      confidence interval [CI], 0.35-0.69 and kappa = 0.62; 95% CI, 0.46-0.78,
      respectively). Expert consensus was more likely to classify a series of fields as
      showing progression than was GPA (P <= 0.002). There was good agreement between
      expert consensus on initial review and reevaluation 4 months later (kappa = 0.77;
      95% CI, 0.65-0.90). CONCLUSIONS: The level of agreement between majority expert
      consensus of subjective determination of visual field progression and GPA is
      fair. In cases of disagreement with GPA, the expert consensus classification was
      usually progression. Access to the results of GPA did not significantly change
      the level of agreement between expert consensus and the GPA result; however,
      expert consensus did change in 11 of 100 cases.

PMID- 22137045
TI  - The future of Alzheimer's disease: the next 10 years.
AB  - Alzheimer's disease (AD) is a fast growing world-wide epidemic. AD is a
      genetically complex, slowly progressive, and irreversible neurodegenerative
      disease of the brain. During decades of asymptomatic progression multiple
      interactive systems, pathways and molecular mechanisms (e.g. protein processing,
      aberrant signaling, inflammation and immune system, lipid transport, endocytosis,
      apoptosis, oxidative damage and response to stress, tau pathology, neuron and
      synapse loss, energy metabolism), contribute to the development of the early
      clinical prodromal stage with episodic memory deficits and to further decline and
      loss of general cognitive functioning during the final syndromal dementia stage.
      The non-mendelian genetically complex "sporadic" AD type is the most common form
      of dementia affecting people usually over the age of 65. Despite considerable
      progress of AD research in recent years and evolving paradigm shifts in both
      pathophysiological concepts as well as in diagnostic criteria fundamental
      challenges have not yet been resolved. The strong age-related incidence, the
      recent failure and complete lack of disease-modifying or preventive therapy that
      may delay onset or substantially affect the pathophysiology of AD, result in an
      enormous burden posed both on individuals, their families and care givers, and
      the societies at large, and these call for urgent concerted worldwide measures.
      Based on the meeting of the German Task Force on Alzheimer's Disease (GTF-AD) in
      Paris on July 19th 2011, the present position paper provides an overview on the
      current state and future developments in epidemiology, pathophysiology, disease
      conceptualization, diagnostic criteria and their use in research and clinical
      practice, as well as preventive and symptomatic therapeutic approaches.
      Particular emphasis is placed on a discussion of the different approaches to
      diagnostics and therapy taken by preventive/public health medicine,
      methodologically advanced academic research propagating the use of sophisticated
      biomarkers, and everyday clinical practice focusing on patient-centered care.
      During the next 10 years, major advances both in early detection as well as in
      therapy and comprehensive AD care seem mandatory. These still unmet needs call
      for ever more concerted and focused efforts in research across the world to
      combat the erupting and as yet uncontrolled epidemic of AD.

PMID- 22137046
TI  - Onwards and upwards.

PMID- 22137047
TI  - An apparently jawless cadaver: a case of post-mortem slippage.
AB  - Passer-by witnesses reported a human cadaver in woodland associated with an
      agricultural college to police in Northern Ireland. The cadaver comprised
      reasonably preserved feet, legs and pelvis, with poorly preserved arms and torso,
      lying with the torso down-slope abutting a fallen tree. A search of the area
      around the torso, and for some 20m around, failed to find the cranium and
      mandible. The mandible was found, embedded inside the chest cavity. The cranium
      was found some 30m away. The victim was later identified as a 24-year old drug
      addict who had absconded from a local hospital. Mapping of the area led us to
      speculate that he had tripped and fallen down-slope: other reasons for the body
      location were also considered. After death, the cadaver had further slipped down
      slope forcing the mandible into the chest cavity: slippage of human remains is
      well-known in forensic and archaeological literature but not well documented.
      Knowledge of this process of cadaver 'slip' may save wasted police resources in
      future similar environments where the mandible, and possible other nearby bones
      appear missing yet are inside the body.

PMID- 22137048
TI  - On the frequency of occurrence of a peculiar polyester fibre type found in blue
      denim textiles.
AB  - In a double murder investigation, the victims were found after a prolonged stay
      in a drainage canal. In spite of the expectations, fibre examination established
      a multitude of primary and secondary transferred fibres. One of these fibre types
      was a colourless polyester fibre possessing a blue coloured molten fibre end.
      These matched one of the types present in the suspect's blue denim trousers. The
      aim of this study was to verify the rarity of this peculiar fibre type and more
      precisely its presence in blue denim textiles. Over five hundred different blue
      jeans textiles were examined and only one of these presented exactly the same
      type. The comparison involved microscopy, microspectrophotometry in the visible
      range and Raman spectroscopy. The results indicate this fibre type is extremely
      rare in a blue jeans fabrics and that "standard" blue denim should not be
      disregarded in case work.

PMID- 22137049
TI  - Dichroism measurements in forensic fibre examination. Part 2 - dyed polyamide,
      wool and silk fibres.
AB  - A number of dyed polyamide, wool and silk samples were examined with plane
      polarized light on their dichroic behavior by optical light microscopy (OLM) and
      microspectrophotometry with plane polarized light (MSP-PPL). It was found that
      most of these acid dyed peptidic fibres possess dichroism, but these are weaker
      than the effects previously described for polyester fibres. The small effects may
      be not observed, especially for wool, but these can be measured using MSP-PPL. In
      the three peptidic fibre classes, for the first time, a so called "inverse
      dichroism" is observed which appears in the absorption spectra as a hyperchromic
      effect.

PMID- 22137050
TI  - Dichroism measurements in forensic fibre examination. Part 3 - dyed cotton and
      viscose fibres.
AB  - A number of dyed cellulosic fibres were examined with plane polarized light on
      their dichroic behavior by microscopy and microspectrophotometry (MSP-PPL).
      Significant dichroic effects (mostly hypochromic effects and hypsochromic bands
      shifts) were reported. The effect is related to the chemical structure: some dye
      structures always possess dichroism (azo, stilbene, thiazole and oxazine), some
      dyes demonstrate sometimes dichroic effects (anthraquinoid, indigoid) while other
      structures never demonstrate dichroic effects (sulphur, diphenylmethanes,
      triarylmethanes, phthalocyanines). In some cases a different dichroic behavior
      was found for the same dyes applied on cotton and on viscose.

PMID- 22137051
TI  - The persistence of fibres on skin in an outdoor deposition crime scene scenario.
AB  - Textile fibres were transferred to a pig skin carcass and their persistence
      determined at daily intervals for up to a 12 day period during which time the
      carcass was left outdoors exposed to the prevailing weather conditions and animal
      activity. In the absence of strong winds and precipitation, the loss of fibres
      was found to be exponential. Stronger winds and heavier precipitation caused an
      increase in the rate of loss of fibres. The results of this study showed that the
      majority of fibres transferred to a body deposited outdoors, can be expected to
      be lost after the first 2 days, however, none of the experiments performed
      resulted in a complete loss of fibres, even after 12 days exposure. These
      persistence characteristics differed from those observed in a similar study using
      small sections of skin, rather than carcasses. The implications of the results of
      the present study in relation to the examination of fibre evidence in cases of
      homicide are discussed.

PMID- 22137052
TI  - Recovery of human DNA profiles from poached deer remains: a feasibility study.
AB  - Poaching is a crime that occurs worldwide and can be extremely difficult to
      investigate and prosecute due to the nature of the evidence available. If a
      species is protected by international legislation such as the Convention on
      International Trade in Endangered Species of Wild Fauna and Flora then simply
      possessing any part of that species is illegal. Previous studies have focused on
      the identification of endangered species in cases of potential poaching.
      Difficulties arise if the poached animal is not endangered. Species such as deer
      have hunting seasons whereby they can legally be hunted however poaching is the
      illegal take of deer, irrespective of season. Therefore, identification of deer
      alone has little probative value as samples could have originated from legal
      hunting activities in season. After a deer is hunted it is usual to remove the
      innards, head and lower limbs. The limbs are removed through manual force and
      represent a potential source of human touch DNA. We investigate the potential to
      recover and profile human autosomal DNA from poached deer remains. Samples from
      the legs of ten culled deer were obtained (40 in total) using minitapes. DNA from
      samples was extracted, quantified and amplified to determine if it would be
      possible to recover human STR profiles. Low quantification data led to the use of
      an extended PCR cycling protocol of 34 cycles. Samples from seven deer amplified,
      however some samples were excluded from further analysis due to 'drop in' alleles
      or the low level of successfully amplified loci. Samples from five deer could be
      further analysed and gave match probabilities ranging from 6.37*10(-3) to
      9.53*10(-11). This study demonstrates the potential of recovering human touch DNA
      from poached animal remains. There is the potential for this test to be used in
      relation to other species of poached remains or other types of wildlife crimes.
      This is the first time, to our knowledge, that human STR profiling has been
      successfully applied to touch DNA in regards to simulated wildlife crime.

PMID- 22137053
TI  - Ultra-trace analysis of illicit drugs from transfer of an electrostatic lift.
AB  - This article introduces a method of collecting and analysing drug residues that
      integrates both electrostatic lifting and nanomanipulation-coupled to nanospray
      ionization mass spectrometry. The application of this hyphenated technique
      exhibits a useful means of collection and extraction of drug residues with ease
      and efficiency along with decreased limits of detection. From this method, it
      will be shown how increased sensitivity of analysis and lower limits of detection
      for drug analysis can be achieved. The same principles that allow lifting of dust
      prints by electrostatic lifting can be applied to lifting drug residues. Probing
      of the drug residues by nanomanipulation occurs directly from the lift, which
      provides a great platform for extraction. Nanomanipulation-coupled to nanospray
      ionization-mass spectrometry has been used for the extraction of trace analytes
      in previous experiments and is known as a very sensitive technique for the
      detection of ultra-trace residue. This method will demonstrate the electrostatic
      lifting of drug residue particles from a surface followed by extraction and
      ionization with nanomanipulation-nanospray ionization. The utility of this novel
      methodology allows for a more productive analysis when presented with ultra-trace
      amounts of sample.

PMID- 22137054
TI  - Subjectivity and bias in forensic DNA mixture interpretation.
AB  - The objectivity of forensic science decision making has received increased
      attention and scrutiny. However, there are only a few published studies
      experimentally addressing the potential for contextual bias. Because of the
      esteem of DNA evidence, it is important to study and assess the impact of
      subjectivity and bias on DNA mixture interpretation. The study reported here
      presents empirical data suggesting that DNA mixture interpretation is subjective.
      When 17 North American expert DNA examiners were asked for their interpretation
      of data from an adjudicated criminal case in that jurisdiction, they produced
      inconsistent interpretations. Furthermore, the majority of 'context free' experts
      disagreed with the laboratory's pre-trial conclusions, suggesting that the
      extraneous context of the criminal case may have influenced the interpretation of
      the DNA evidence, thereby showing a biasing effect of contextual information in
      DNA mixture interpretation.

PMID- 22137055
TI  - Reflection and direction: Founder's Lecture, Spring 2011 CAC, Long Beach, CA.

PMID- 22137056
TI  - Re: expressing evaluative opinions; a position statement.

PMID- 22137057
TI  - Response to Aitken et al. on R v T.

PMID- 22137059
TI  - Gold nano particle decorated graphene core first generation PAMAM dendrimer for
      label free electrochemical DNA hybridization sensing.
AB  - A novel first generation (G1) poly(amidoamine) dendrimer (PAMAM) with graphene
      core (GG1PAMAM) was synthesized for the first time. Single layer of GG1PAMAM was
      immobilized covalently on mercaptopropionic acid (MPA) monolayer on Au
      transducer. This allows cost effective and easy deposition of single layer
      graphene on the Au transducer surface than the advanced vacuum techniques used in
      the literature. Au nano particles (17.5 nm) then decorated the GG1PAMAM and used
      for electrochemical DNA hybridization sensing. The sensor discriminates
      selectively and sensitively the complementary double stranded DNA (dsDNA,
      hybridized), non-complementary DNA (ssDNA, un-hybridized) and single nucleotide
      polymorphism (SNP) surfaces. Interactions of the MPA, GG1PAMAM and the Au nano
      particles were characterized by Ultra Violet (UV), Fourier Transform Infrared
      (FTIR), Raman spectroscopy (RS), Thermo gravimetric analysis (TGA), Scanning
      Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Cyclic Voltmetric (CV),
      Impedance spectroscopy (IS) and Differntial Pulse Voltammetry (DPV) techniques.
      The sensor showed linear range 1*10(-6) to 1*10(-12) M with lowest detection
      limit 1 pM which is 1000 times lower than G1PAMAM without graphene core.

PMID- 22137060
TI  - Quantum dots-based multifunctional dendritic superstructure for amplified
      electrochemiluminescence detection of ATP.
AB  - A novel multifunctional dendrimeric CdSe-CdS-Quantum dots (QDs) hybrid
      superstructure with highly intense electrochemiluminescence (ECL), fluorescence
      and excellent magnetic property is prepared for the first time, and successfully
      applied to amplified ECL assays of ATP using DNA cycle amplification technique.
      The magnetic nanoparticles (MNPs) were firstly assembled with unique dendrimer
      nanoclusters (NCs), then large numbers of QDs were labeled onto the dendrimer
      NCs, the superstructure exhibits highly enhanced ECL and fluorescence than the
      pure QDs. Remarkable ECL quenching of the nanocomposites by gold nanoparticles
      (GNPs) was observed, based on which a novel strategy for highly sensitive ATP
      detection was developed by cycle amplification technique. Furthermore, the
      nanocomposites with excellent magnetic properties can be easily labeled,
      separated and immobilized onto a magnetic electrode. In particular, all the
      procedures such as linking GNPs, sensing target and DNA cycle amplification were
      directly accomplished on the nanocomposites, which is more rapid, convenient,
      complete and has better reproducibility than the conventional methods on
      electrode. To the best of our knowledge, this is the first report on the
      multifunctional QDs superstructure with highly intense ECL, fluorescence,
      excellent magnetism and its ECL biosensing, which opens a new pathway for
      developing QD-based nanocomposites for broad applications in ECL bioassays and
      optical imaging.

PMID- 22137061
TI  - High sensitivity carbon nanotube based electrochemiluminescence sensor array.
AB  - Ink jet printed carbon nanotube forest arrays capable of detecting picomolar
      concentrations of immunoglobulin G (IgG) using electrochemiluminescence (ECL) are
      described. Patterned arrays of vertically aligned single walled carbon nanotube
      (SWCNT) forests were printed on indium tin oxide (ITO) electrodes. Capture anti
      IgG antibodies were then coupled through peptide bond formation to acidic
      functional groups on the vertical nanotubes. IgG immunoassays were performed
      using silica nano particles (Si NP) functionalized with the ECL luminophore
      [Ru(bpy)(2)PICH(2)](2+)], and IgG labelled G1.5 acid terminated PAMAM dendrimers.
      PAMAM is poly(amido amine), bpy is 2,2'-bipyridyl and PICH(2) is (2-(4
      carboxyphenyl)imidazo[4,5-f][1,10]phenanthroline). The carboxyl terminal of
      [Ru(bpy)(2)PICH(2)](2+) (fluorescence lifetime ~ 682+/-5 ns) dye was covalently
      coupled to amine groups on the 800 nm diameter silica spheres in order to produce
      significant ECL enhancement in the presence of sodium oxalate as co-reactant in
      PBS at pH 7.2). Significantly, this SWCNT-based sensor array shows a wide linear
      dynamic range for IgG coated spheres (10(6) to 10(12) spheres) corresponding to
      IgG concentrations between 20 pM and 300 nM. A detection limit of 1.1+/-0.1 pM
      IgG is obtained under optimal conditions.

PMID- 22137062
TI  - Determinants of return to work after carpal tunnel release.
AB  - PURPOSE: The determinants of time to return to work-a common measure of treatment
      effectiveness-are incompletely defined. Our primary hypothesis was that
      employment circumstances are the strongest determinant of earlier return to work.
      Our secondary hypothesis was that return to work in patients with desk-based jobs
      is predicted by patient expectations and other psychosocial factors. METHODS: We
      enrolled 65 employed patients with limited incision open carpal tunnel release in
      a prospective cohort study. Patients completed validated measures of depression,
      coping strategies, pain anxiety, and job burnout. Heavy lifting was not allowed
      for 1 month after surgery. Return to modified and full work duty was recorded in
      days. Although not specifically an exclusion criterion, none of the patients had
      a workers' compensation claim or other source of secondary gain. RESULTS:
      Patients returned to modified duty an average of 11.8 days and full duty at an
      average of 18.9 days after surgery. Predictors of earlier return to modified duty
      in multivariate analyses included desk-based work and both the number of days
      patients expected to take off and the numbers of days they wanted to take off for
      the entire cohort, with an additional influence from catastrophic thinking in
      desk-based workers. Predictors of earlier return to full duty in multivariate
      analyses included desk-based work and number of days patients expected to take
      off before for the entire cohort, fewer days off desired in non-desk-based
      workers, fewer days off desired and change in work role in desk-based workers,
      and lower pain anxiety in part-time workers. CONCLUSIONS: The most important
      determinant of return to full duty work after limited incision open carpal tunnel
      release is job type, but psychological factors such as patient expectations,
      catastrophic thinking, and anxiety in response to pain also have a role. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 22137063
TI  - Long-term results of forearm shortening and volar radiocarpal capsulotomy for
      wrist flexion deformity in children with amyoplasia.
AB  - PURPOSE: To perform a long-term review of results of forearm shortening
      osteotomies, tenotomy, and volar wrist capsulotomy for treatment of typical wrist
      flexion deformities in children with the amyoplasia form of arthrogryposis, a
      procedure originally reported and described as "most rewarding" by Lexington
      Shriners Hospital for Children in 1965. METHODS: A retrospective review of
      operating room and clinic records was done. An attempt to contact all patients
      produced 1 current follow-up. RESULTS: Nine extremities in 6 patients had
      undergone the procedure. Of the 9 extremities, 3 subsequently underwent salvage
      procedures, 2 had salvage procedures recommended, and 1 had a distal forearm
      fracture angular malunion that compensated for the wrist flexion contracture. The
      charts for the patients with the 3 remaining extremities showed that at 3-year
      follow-up, the wrist flexion contractures had recurred. CONCLUSIONS: Long-term
      follow-up of the procedure shows that the initial improvement in wrist position
      is not maintained. This procedure is not recommended for correction of the wrist
      deformity in amyoplasia. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22137064
TI  - Radiolunate and radioscapholunate arthrodeses as treatments for rheumatoid and
      psoriatic arthritis: long-term follow-up.
AB  - PURPOSE: We evaluated long-term results for radiolunate and radioscapholunate
      arthrodeses for patients with rheumatoid or psoriatic arthritis to determine the
      durability and efficacy of the procedures. The results are described and compared
      with those in the literature. METHODS: We carried out arthrodesis of the
      radiolunate joint (33 wrists) and the radioscapholunate joint (13 wrists) to
      achieve pain reduction and ulnar translation of the carpus in patients with
      rheumatoid (42 wrists) or psoriatic arthritis (4 wrists). At follow-up, 11
      patients (13 wrists) had died, 2 patients (4 wrists) were lost to follow-up, and
      in 6 wrists an additional midcarpal arthrodesis had been performed. We evaluated
      the remaining 23 wrists (19 radiolunate and 4 radioscapholunate, and 1 psoriatic
      arthritic wrist) after a mean of 11 years. RESULTS: Clinical outcome was good,
      with a mean visual analog score of 2 out of 10 for pain, mean grip strength of 13
      kg, and mean range of flexion-extension of 60 degrees . Outcomes as measured by
      questionnaires were good. Radiographs demonstrated deterioration of all
      intracarpal joints as noted by an increased Larsen score and evidence of carpal
      translation. We noted no significant change in carpal height. CONCLUSIONS:
      Despite radiographic progression, radiolunate and radioscapholunate arthrodeses
      yield good clinical results at long-term follow-up. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 22137065
TI  - Do admissions and discharges to long-term care facilities influence hospital
      burden of Clostridium difficile infection?
AB  - BACKGROUND: Substantial geographical clustering of Clostridium difficile
      infection (CDI) outbreaks in hospitals in the USA have previously been
      demonstrated. AIM: To test the hypothesis that hospital burden of CDI is
      associated with admission from and discharge to long-term care facilities
      (LTCFs). METHODS: Hospital discharge data from 19 states in the USA were used to
      identify all patients discharged with a diagnosis of CDI from 1 January 2002 to
      31 December 2004. For every hospital, the proportion of discharges with a
      diagnosis of CDI was calculated, and those above the 90th percentile were
      classified as 'high CDI' hospitals. We tested the association between this
      measure of hospital burden of CDI and the rates of admission from and discharges
      to LTCFs. We adjusted for other hospital level characteristics, case-complexity
      and local population characteristics. FINDINGS: We identified 38,372,951
      discharges during the three-year study period. Of all discharges, 274,311 (0.71%)
      had a primary or secondary diagnosis of CDI. Hospitals had a mean CDI burden of
      7.8 cases per 1000 discharges. High CDI hospitals (N = 610; 10.0%) had a mean CDI
      burden of 34.8 cases per 1000 discharges. Compared to other hospitals, high CDI
      hospitals were more likely to have a high proportion of admissions from or
      discharges to LTCFs. This association persisted after adjustments for other
      hospital characteristics, case-complexity, and area population characteristics.
      CONCLUSION: A high rate of admission from or discharge to LTCFs is associated
      with an increased hospital burden of CDI.

PMID- 22137066
TI  - Meticillin-resistant Staphylococcus aureus is more resistant to vaporized
      hydrogen peroxide than commercial Geobacillus stearothermophilus biological
      indicators.
AB  - BACKGROUND: Vaporized hydrogen peroxide (VHP) is increasingly used in the
      decontamination of hospital isolation rooms. Commercially available
      bioindicators, most frequently Geobacillus stearothermophilus spores, are used to
      assess the efficacy of the decontamination phase. Staphylococcus aureus,
      including meticillin-resistant S. aureus (MRSA), produce catalase, which breaks
      down VHP, therefore potentially making it resistant to the decontamination phase.
      AIM: This investigation was designed to assess the resistance of meticillin
      resistant S. aureus to VHP in comparison with commercially available biological
      indicators loaded with spores. METHODS: Stainless steel indicators were prepared
      with the same loading of MRSA (NCTC 13142) as commercially available indicators
      of G. stearothermophilus (ATCC 7953) (~3.1*10(6) spores) and both indicators were
      exposed to a vapour hydrogen peroxide cycle (750 ppm). At set time-points during
      the exposure period, indicators containing both organisms were removed for
      processing and enumeration to compare survivability. FINDINGS: During the
      exposure period the recovery of MRSA from the coupons was between 1.5 and 3.5
      log(10) higher than the recovery of G. stearothermophilus spores (P<0.05). This
      greater resistance may be due to the production of catalase which could break
      down the hydrogen peroxide, resulting in a reduction of the effectiveness of VHP.
      CONCLUSION: These findings highlight that the reduction achieved with a
      commercially available biological indicator cannot always be extrapolated to
      other micro-organisms. It must be recognized that although gaseous
      decontamination is the final step of the decontamination process, pre-cleaning of
      surfaces must be carried out to reduce the microbial loading being exposed.

PMID- 22137067
TI  - Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of
      randomized, double-blind, placebo-controlled trials.
AB  - BACKGROUND: Previous studies suggest that L-arginine, an amino acid and a
      substrate of nitric oxide synthase, may have blood pressure (BP)-lowering effect.
      Because some studies were performed with limited number of patients with
      hypertension and therefore limited statistical power with sometimes inconsistent
      results, we aimed to examine the effect of oral L-arginine supplementation on BP
      by conducting a meta-analysis of randomized, double-blind, placebo-controlled
      trials. METHODS: PubMed, Cochrane Central Register of Controlled Trials, and the
      ClinicalTrials.gov databases were searched through June 2011 to identify
      randomized, double-blind, placebo-controlled trials of oral L-arginine
      supplementation on BP in humans. We also reviewed reference lists of obtained
      articles. Either a fixed-effects or, in the presence of heterogeneity, a random
      effects model was used to calculate the combined treatment effect. RESULTS: We
      included 11 randomized, double-blind, placebo-controlled trials involving 387
      participants with oral L-arginine intervention ranging from 4 to 24 g/d. Compared
      with placebo, L-arginine intervention significantly lowered systolic BP by 5.39
      mm Hg (95% CI -8.54 to -2.25, P = .001) and diastolic BP by 2.66 mm Hg (95% CI 
      3.77 to -1.54, P < .001). Sensitivity analyses restricted to trials with a
      duration of 4 weeks or longer and to trials in which participants did not use
      antihypertensive medications yielded similar results. Meta-regression analysis
      suggested an inverse, though insignificant (P = .13), relation between baseline
      systolic BP and net change in systolic BP. CONCLUSIONS: This meta-analysis
      provides further evidence that oral L-arginine supplementation significantly
      lowers both systolic and diastolic BP.

PMID- 22137068
TI  - Rationale and design of the treatment of preserved cardiac function heart failure
      with an aldosterone antagonist trial: a randomized, controlled study of
      spironolactone in patients with symptomatic heart failure and preserved ejection
      fraction.
AB  - BACKGROUND: Despite increasing prevalence of heart failure (HF) in patients with
      preserved ejection fraction (PEF), there are no available therapies proven to
      reduce morbidity and mortality. Aldosterone, a potent stimulator of myocardial
      and vascular fibrosis, may be a key mediator of HF progression in this population
      and is therefore an important therapeutic target. OBJECTIVE: The TOPCAT trial is
      designed to evaluate the effect of spironolactone, an aldosterone antagonist, on
      morbidity, mortality, and quality of life in patients with HF-PEF. METHODS: Up to
      3,515 patients with HF-PEF will be randomized in double-blind fashion to
      treatment with spironolactone (target dose 30 mg daily) or matching placebo.
      Eligible patients include those with age >=50 years, left ventricular ejection
      fraction >=45%, symptomatic HF, and either a hospitalization for HF within the
      prior year or an elevated natriuretic peptide level (B-type natriuretic peptide
      >=100 pg/mL or N-terminal pro-B-type natriuretic peptide >=360 pg/mL) within the
      60 days before randomization. Patients with uncontrolled hypertension and those
      with known infiltrative or hypertrophic cardiomyopathy are excluded. The primary
      end point is the composite of cardiovascular death, hospitalization for HF, or
      aborted cardiac arrest. Key secondary end points include quality of life,
      nonfatal cardiovascular events, and new-onset atrial fibrillation. Ancillary
      studies of echocardiography, tonometry, and cardiac biomarkers will provide more
      insight regarding this understudied population and the effects of spironolactone
      therapy. CONCLUSION: TOPCAT is designed to assess definitively the role of
      spironolactone in the management of HF-PEF.

PMID- 22137069
TI  - Developing mechanistic insights into cardiovascular cell therapy: Cardiovascular
      Cell Therapy Research Network Biorepository Core Laboratory rationale.
AB  - Moderate improvements in cardiac performance have been reported in some clinical
      settings after delivery of bone marrow mononuclear cells to patients with
      cardiovascular disease. However, mechanistic insights into how these cells impact
      outcomes are lacking. To address this, the National Heart, Lung and Blood
      Institute (NHLBI) Cardiovascular Cell Therapy Research Network (CCTRN)
      established a Biorepository Core for extensive phenotyping and cell function
      studies and storing bone marrow and peripheral blood for 10 years. Analyzing cell
      populations and cell function in the context of clinical parameters and clinical
      outcomes after cell or placebo treatment empower the development of novel
      diagnostic and prognostics. Developing such biomarkers that define the safety and
      efficacy of cell therapy is a major Biorepository aim.

PMID- 22137070
TI  - Survival after acute myocardial infarction (SAMI) study: the design and
      implementation of a positive deviance study.
AB  - Positive deviance studies combining qualitative and quantitative designs-a mixed
      methods approach-can discover strategies to produce exemplary performance. We
      present the SAMI study, a national positive deviance study to discover hospital
      strategies associated with lower 30-day hospital risk-standardized mortality
      rates (RSMRs). There is marked variation across hospitals in 30-day hospital
      RSMRs for patients with acute myocardial infarction and little information about
      what accounts for differences in performance. We first conducted a qualitative
      study of hospitals in the United States (n = 11; 158 key staff) that ranked in
      the top 5% of RSMRs for each of the 2 most recent years of data (2005-2006 and
      2006-2007) from the Centers for Medicare & Medicaid Services at the time of
      sample selection and in the bottom 5% for contrast, with diversity among
      hospitals in key characteristics. Using hypotheses generated in this qualitative
      stage, we constructed a quantitative survey that was administered in a cross
      sectional study of acute care hospitals in the United States operating from July
      1, 2005, through June 30, 2008, that publicly reported Centers for Medicare &
      Medicaid Services data for RSMRs during this time. We included hospitals with at
      least 75 acute myocardial infarction discharges during the 3-year period. Of the
      600 hospitals we attempted to contact, 10 had closed, leaving a final sample of
      590, of which 537 responded (91%). This type of study, using a positive deviance
      approach and mixed-methods design, can generate and test hypotheses about factors
      most strongly associated with exemplary performance based on practices currently
      in use.

PMID- 22137071
TI  - Regional differences in clinical profile, quality of care, and outcomes among
      Hispanic patients hospitalized with acute myocardial infarction in the Get with
      Guidelines-Coronary Artery Disease (GWTG-CAD) registry.
AB  - BACKGROUND: Although Hispanics constitute the largest minority in the United
      States, it is unknown whether regional differences in quality of care and
      outcomes exist among Hispanic patients hospitalized with acute myocardial
      infarction (MI). METHODS: Using the GWTG-CAD Registry, clinical characteristics,
      conformity with quality measures, and in-hospital outcomes were assessed among
      Hispanic patients from different geographic regions admitted for acute MI in
      participating hospitals. RESULTS: A total of 11,299 Hispanic patients treated for
      acute MI at 277 hospitals from 4 regions were included in the study. Midwestern
      Hispanics were more likely to be younger, with male predominance in all regions.
      Northeastern Hispanics were more often insured with Medicaid. All subgroups
      showed high rates of hypertension, dyslipidemia, diabetes, and smoking, with the
      highest rates observed in the northeast region. Northeastern Hispanics were more
      likely to be discharged on angiotensin-converting enzyme inhibitors/angiotensin
      receptor blockers, beta-blockers, and statin or other lipid-lowering therapy. No
      significant regional differences were observed in aspirin, clopidogrel, and
      guideline-recommended door-to-balloon and door-to-thrombolysis times. Although
      Hispanics in the south and northeast were more likely to have a longer hospital
      stay compared with the west, there were no regional differences in in-hospital
      mortality. CONCLUSIONS: Among Hispanics with acute MI enrolled in the GWTG-CAD
      program, there were modest regional differences in clinical profile; high rates
      of use and, with few exceptions, no regional differences in guideline-recommended
      therapies; and no regional variation in in-hospital mortality.

PMID- 22137072
TI  - The kinetics of integrilin limited by obesity: a multicenter randomized
      pharmacokinetic and pharmacodynamic clinical trial.
AB  - BACKGROUND: KILO tested 2 novel weight-based eptifibatide dosing strategies
      compared with standard dosing in obese patients undergoing elective percutaneous
      coronary intervention (PCI). Eptifibatide dosing is weight adjusted for patients
      up to 121 kg. Patients above this weight receive the same maximal dose, although
      it is unknown if this provides adequate eptifibatide concentration or platelet
      inhibition. METHODS: Sixty-seven patients weighing >=125 kg undergoing elective
      PCI were randomized to 1 of 3 eptifibatide dosing regimens: standard dosing using
      a weight of 121 kg, actual body weight (ABW)-based dosing with no upper limit, or
      ideal body weight (IBW)-based dosing. Boluses of 180 MUg/kg were given 10 minutes
      apart, followed by a 2.0 MUg/kg per minute infusion. Plasma eptifibatide
      concentrations were drawn at 12 to 18 hours after initiating the infusion.
      Platelet aggregation was assessed at baseline and 10 minutes after the second
      bolus. RESULTS: Sixty-seven patients were randomized to standard (n = 22), ABW (n
      = 23), or IBW (n = 22) dosing. The median (25th, 75th) steady-state plasma
      eptifibatide concentrations were 1,740 ng/mL (1,350, 2,350), 1,780 ng/mL (1,510,
      2,350), and 1,055 ng/mL (738, 1,405), respectively (P < .001). Ten-minute median
      (25th, 75th) platelet aggregation units were 7 (0, 21), 2 (0, 8), and 14 (8, 20),
      respectively (P = .001). CONCLUSIONS: Actual body weight eptifibatide dosing
      leads to higher plasma concentrations and greater platelet inhibition than
      standard or IBW dosing in obese patients undergoing PCI. Current recommendations
      for eptifibatide dosing may be inadequate in patients >121 kg. Further study is
      warranted to define the optimal dosing of eptifibatide and other medications in
      obese patients.

PMID- 22137073
TI  - Benefit of exercise therapy for systolic heart failure in relation to disease
      severity and etiology-findings from the Heart Failure and A Controlled Trial
      Investigating Outcomes of Exercise Training study.
AB  - BACKGROUND: This post hoc analysis of the HF-ACTION cohort explores the primary
      and secondary results of the HF-ACTION study by etiology and severity of illness.
      METHODS: HF-ACTION randomized stable outpatients with reduced left ventricular
      (LV) function and heart failure (HF) symptoms to either supervised exercise
      training plus usual care or to usual care alone. The primary outcome was all
      cause mortality or all-cause hospitalization; secondary outcomes included all
      cause mortality, cardiovascular mortality or cardiovascular hospitalization, and
      cardiovascular mortality or HF hospitalization. The interaction between treatment
      and risk variable, etiology or severity as determined by risk score, New York
      Heart Association class, and duration of cardiopulmonary exercise test was
      examined in a Cox proportional hazards model for all clinical end points.
      RESULTS: There was no interaction between etiology and treatment for the primary
      outcome (P = .73), cardiovascular (CV) mortality or CV hospitalization (P = .59),
      or CV mortality or HF hospitalization (P = .07). There was a significant
      interaction between etiology and treatment for the outcome of mortality (P =
      .03), but the interaction was no longer significant when adjusted for HF-ACTION
      adjustment model predictors (P = .08). There was no significant interaction
      between treatment effect and severity, except a significant interaction between
      cardiopulmonary exercise duration and training was identified for the primary
      outcome of all-cause mortality or all-cause hospitalization. CONCLUSION:
      Consideration of symptomatic (New York Heart Association classes II to IV)
      patients with HF with reduced LV function for participation in an exercise
      training program should be made independent of the cause of HF or the severity of
      the symptoms.

PMID- 22137074
TI  - Treadmill testing improves survival prediction models in pulmonary arterial
      hypertension.
AB  - BACKGROUND: Six-minute walk distance (6MWD) is used in the REVEAL equation to
      predict 1-year survival for patients with pulmonary arterial hypertension. We
      sought to determine whether exercise treadmill testing (ETT) could be used in its
      place. METHODS: This was a single-center study in which 449 patients were
      enrolled. The variables predictive of survival in the REVEAL equation were
      evaluated and compared with survival predicted by the REVEAL equation without an
      exercise measure and a revised equation using ETT. RESULTS: The addition of ETT
      to the equation improved the predictive ability of the REVEAL equation in the
      high- and low-risk patient groups. CONCLUSION: The study findings suggest that
      the addition of ETT parameters to the REVEAL prognostic equation improves the
      predictive value of the equation when 6-minute walk distance is unavailable.

PMID- 22137075
TI  - Platelet reactivity in patients with chronic kidney disease receiving adjunctive
      cilostazol compared with a high-maintenance dose of clopidogrel: results of the
      effect of platelet inhibition according to clopidogrel dose in patients with
      chronic kidney disease (PIANO-2 CKD) randomized study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a factor of low response to
      clopidogrel. We sought to assess the functional impact of cilostazol in CKD
      patients with undergoing hemodialysis. METHODS: Seventy-four patients with CKD
      undergoing hemodialysis and percutaneous coronary intervention were enrolled.
      Patients were randomly assigned to receive clopidogrel (75 mg/d [group 1, n =
      24]), high-maintenance dose of clopidogrel (150 mg/d [group 2, n = 25]), or
      clopidogrel (75 mg/d) with cilostazol (200 mg/d [group 3, n = 25]) for 14 days.
      Another 50 patients with normal renal function undergoing percutaneous coronary
      intervention were treated with 75 mg of clopidogrel and served as the control
      group. Platelet function was evaluated before and after antiplatelet therapy with
      light transmittance aggregometry and with VerifyNow P2Y12 assay (Accumetrics, San
      Diego, CA). Platelet activation markers (soluble CD40 ligand and soluble P
      selectin) were also assessed. RESULTS: The baseline platelet function
      measurements were similar in the 3 groups of patients; however, the CKD groups
      had significantly higher platelet aggregation activity compared with the control
      groups. The rate of high on-treatment platelet reactivity was significantly lower
      in group 3 than in groups 1 and 2 (10% vs 43% vs 32%, respectively; P < .05).
      After 14 days of antiplatelet therapy, the changes in plasma soluble CD40 ligand
      and soluble P-selectin levels were significantly higher in group 3 compared with
      groups 1 and 2 (P < .01); however, there were no significant differences in
      platelet function and activation markers between groups 1 and 2. CONCLUSIONS:
      Adjunctive cilostazol improves platelet inhibition compared with 75 or 150 mg of
      clopidogrel in CKD patients undergoing hemodialysis.

PMID- 22137076
TI  - Effects of atorvastatin pretreatment on infarct size in patients with ST-segment
      elevation myocardial infarction undergoing primary percutaneous coronary
      intervention.
AB  - BACKGROUND: Atorvastatin pretreatment has been reported to reduce myocardial
      damage in patients undergoing percutaneous coronary intervention (PCI). We sought
      to investigate the effect of atorvastatin pretreatment on infarct size in
      patients with ST-segment elevation myocardial infarction (STEMI). METHODS:
      Patients undergoing primary PCI for ST-segment elevation myocardial infarction
      within 12 hours after symptom onset were randomized to an atorvastatin group (80
      mg before PCI and for 5 days after PCI [n = 89]) or a control group (10 mg daily
      after PCI [n = 84]). The primary end point was infarct size measured by
      technetium Tc 99m tetrofosmin single-photon emission computed tomography between
      days 5 and 14. RESULTS: Baseline clinical, angiographic, and procedural
      characteristics were not significantly different between groups except for age
      and current smoking status. There was no significant difference in infarct size
      (as a percentage of the left ventricle) between groups (22.2% +/- 15.5% in the
      atorvastatin group vs 21.6% +/- 15.4% in the control group, P = .79). The median
      infarct size was 19.0% (interquartile range 9.0-32.0) in the atorvastatin group
      and 18.0% (9.3-32.5) in the control group (P = .76). Achievement of myocardial
      blush grade 2/3 and complete ST-segment resolution at 60 minutes after PCI
      occurred with similar frequency (72.8% vs 81.9%, P = .33 and 43.2% vs 47.5%, P =
      .57, respectively). CONCLUSIONS: Pretreatment with high-dose atorvastatin
      followed by further treatment for 5 days did not reduce infarct size measured by
      single-photon emission computed tomography in patients undergoing primary PCI.

PMID- 22137077
TI  - Is cardiac catheterization necessary before initial management of patients with
      stable ischemic heart disease? Results from a Web-based survey of cardiologists.
AB  - BACKGROUND: It is unknown whether preconceived beliefs regarding the need for
      cardiac catheterization and revascularization in patients with stable ischemic
      heart disease (SIHD) would preclude a study randomizing patients with significant
      ischemia to a conservative strategy. Given the widespread practice of performing
      revascularization in patients with SIHD, we assessed the feasibility of
      conducting a randomized trial comparing initial invasive and conservative
      strategies in patients with SIHD and moderate or severe ischemia. METHODS: An
      online survey to cardiologists queried their willingness to enroll a sample
      patient with frequent stable angina, >10% myocardial ischemia, and normal
      ejection fraction into a randomized trial with a 50% chance of being
      conservatively managed without cardiac catheterization. RESULTS: Among 499
      respondents, 57% (95% CI 53%-62%) were willing to enroll the patient. Among 207
      cardiologists unwilling to enroll, 55% (95% CI 48%-61%) would be willing if they
      knew the patient did not have very high-risk features on stress imaging, yielding
      a total of 80% (95% CI 76%-83%) of cardiologists willing to enroll. No
      differences were observed among different types of cardiologists (interventional,
      invasive/noninterventional, and noninvasive). Seventy-one percent (95% CI 67%
      75%) were more likely to try initial medical therapy after the publication of the
      Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation
      trial results. CONCLUSIONS: Most surveyed cardiologists were willing to enroll
      SIHD patients with at least moderate ischemia into a trial with an initial
      noninvasive strategy arm. These findings support the feasibility of planning a
      large-scale trial to test the role of cardiac catheterization and
      revascularization in the initial management of SIHD patients with moderate or
      severe ischemia.

PMID- 22137078
TI  - Relationship between angiographic dynamic and densitometric assessment of
      myocardial reperfusion and survival in patients with acute myocardial infarction
      treated with primary percutaneous coronary intervention: the harmonizing outcomes
      with revascularization and stents in AMI (HORIZONS-AMI) trial.
AB  - OBJECTIVES: We evaluated 2 different methods of assessing tissue myocardial
      perfusion (TMP) and its impact on long-term mortality in patients with ST-segment
      elevation myocardial infarction (STEMI). BACKGROUND: Although primary
      percutaneous coronary intervention restores brisk epicardial flow in
      approximately 90% of patients with STEMI, normal TMP is less commonly achieved.
      Tissue myocardial perfusion has been shown to correlate mostly with early
      clinical outcomes. METHODS: We analyzed the outcomes of 3,267 patients in the
      HORIZONS-AMI study according to final TMP, assessed by angiographic dynamic (Dyn)
      and densitometric (Den) methods. Multivariable analysis was performed to identify
      the independent influence of TMP grade 2/3 on late survival. RESULTS: Dyn TMP 2/3
      was achieved in 2,600 patients (79.6%), whereas Den TMP 2/3 was achieved in 2,483
      (76.0%). Mortality was significantly lower in those with Dyn TMP 2/3 compared
      with TMP 0/1 at 30 days (1.1% vs 6.9%, P < .0001) and at 3 years (5.1% vs 11.2%,
      P < .0001). Similar results were obtained with Den TMP. Dyn TMP 2/3 was an
      independent predictor of mortality at both time points (HR 0.21, 95% CI 0.12
      0.37, P < .0001 and HR 0.53, 95% CI 0.38-0.73, P < .0001, respectively), as was
      Den TMP. Survival was comparable in patients with TMP 2 and TMP 3. CONCLUSIONS:
      Angiographic TMP can be assessed reliably using either Dyn or Den methods and is
      a powerful, independent predictor of early and late mortality after primary
      percutaneous coronary intervention in STEMI.

PMID- 22137079
TI  - Trends and predictors of length of stay after primary percutaneous coronary
      intervention: a report from the CathPCI registry.
AB  - BACKGROUND: Post hoc analyses of clinical trials suggest that certain patients
      are eligible for early discharge after ST-segment elevation myocardial
      infarction. The extent to which ST-segment elevation myocardial infarction
      patients are discharged early after primary percutaneous coronary intervention
      (PPCI) in current practice is unknown. METHODS: We examined 115,113 patients in
      the CathPCI Registry to assess temporal trends in length of stay (LOS) after
      PPCI. Baseline characteristics were compared between patients with LOS <=2 and >2
      days. Predictors of LOS >2 days were determined by logistic regression and
      adjusted for clustering among centers. Patterns of discharge within 2 days for
      low-risk patients with no inhospital complications were examined. RESULTS: From
      January 2005 through March 2009, mean LOS (4.0 +/- 3.0 to 3.6 +/- 2.7 days) (P
      for trend <.001) and the proportion of patients discharged after 2 days decreased
      (72.0%-65.9%), while predicted inhospital mortality risk remained unchanged.
      Patients with LOS >2 days (n = 77,471; 67.3%) were older and more likely to have
      had an intra-aortic balloon pump, cardiogenic shock, transfusions, and post-PPCI
      complications. Of 958 hospitals, 437 (45.6%) discharged at least half of their
      low-risk patients with no inhospital complications within 2 days. CONCLUSIONS:
      While the predicted risk profile has remained stable, there has been a
      significant decrease in LOS after PPCI. Nevertheless, hospitals vary in
      discharging low-risk and uncomplicated patients early. Discharge within 2 days
      was associated with specific patient, procedure, and hospital factors. Further
      study is needed to determine the safety of early discharge among patients
      undergoing PPCI.

PMID- 22137080
TI  - Temporal trends in gastrointestinal bleeding associated with percutaneous
      coronary intervention: analysis of the 1998-2006 Nationwide Inpatient Sample
      (NIS) database.
AB  - BACKGROUND: Gastrointestinal bleeding (GIB) after percutaneous coronary
      intervention (PCI) for acute coronary syndrome (ACS) and coronary artery disease
      (CAD) is associated with high morbidity and mortality. METHODS: The NIS database
      from 1998 to 2006 was used to identify 1,216,759 PCIs performed for ACS and CAD.
      We sought to analyze temporal trends in the incidence and in-hospital outcomes of
      GIB associated with PCI along with its predictors. RESULTS: The overall incidence
      of GIB was 1.04% (95% confidence interval (CI), 1.02%-1.06%). The incidence of
      GIB decreased over the study period (P for trend <.0001). The overall mortality
      in the GIB group was 6.0% (95% CI, 5.6%-6.4%). The adjusted OR for in-hospital
      mortality and GIB was 4.70 (95% CI, 4.23-5.23; P < .0001); this remained high and
      essentially unchanged over the study period. Independent predictors of GIB
      included rectum/anal cancer (OR, 4.64; 95% CI, 3.20-6.73; P < .0001), stomach
      cancer (OR, 2.74; 95% CI, 1.62-4.66; P = .0002), esophageal cancer (OR, 1.99; 95%
      CI, 1.08-3.69; P = .0288), colon cancer (OR, 1.69; 95% CI, 1.43-2.02; P < .0001),
      congestive heart failure (OR, 1.43; 95% CI, 1.35-1.52; P < .0001), and acute
      myocardial infarction (OR, 1.23; 95% CI, 1.13-1.35; P < .0001). CONCLUSIONS:
      Although the incidence of GIB associated with PCI decreased from 1998 to 2006 in
      the face of aggressive therapies for ACS and CAD, the risk of GIB-associated
      death remained high. Underlying GI malignancy is a significant independent
      predictor of GIB associated with PCI; identifying these patients may reduce the
      rate of GIB.

PMID- 22137081
TI  - Risk of target lesion failure in relationship to vessel angiographic geometry and
      stent conformability using the second generation of drug-eluting stents.
AB  - BACKGROUND: Vessel angulation and large changes in vessel geometry after stent
      implantation have been associated with an increased risk of target lesion failure
      (TLF) using bare-metal stents. Second-generation drug-eluting stents (DES)offer
      superior conformability and inhibition of neointima. The aim of the study is to
      investigate the relationship between pre and post-implant vessel geometry and the
      occurrence of TLF at 1 year after treatment with second-generation DES; and to
      compare the conformability of Resolute and Xience stents. METHODS: The RESOLUTE
      All-Comers trial randomized 2292 patients (3366 lesions) to Resolute zotarolimus
      DES (Medtronic CardioVascular) or Xience everolimus-DES (Abbott Vascular). At 1
      year, 176 lesions (121 patients)presented with TLF; a composite of cardiac death,
      acute myocardial infarction (AMI) and target lesion revascularization (TLR).
      Lesions with TLF were matched with 176 lesions (168 patients) without TLF
      adjusting for clinical and procedural characteristics. The number of bends,
      vessel curvature and angulation were assessed with quantitative coronary
      angiography pre and post-implantation. The absolute difference post minus pre
      implantation was used as a surrogate of stent conformability. RESULTS: At pre
      implantation, lesions without and with TLF had similar numbers of bends/lesion
      (1.81 vs 1.74; P = .35), vessel curvature (0.295 cm(-1) vs 0.363 cm(-1); P = .13)
      and vessel angulation (46.3 degrees  vs 43.5 degrees ; P = .80), respectively.
      Lesions without and with TLR also had similar numbers of bends/lesion (1.39 vs
      1.39; P = .83), vessel curvature (0.368 cm(-1) vs 0.325 cm(-1); P = .33) and
      angulation (40.2 degrees  vs 37.2 degrees ; P = .19). Lesions without and with in
      hospital AMI also presented with similar number of bends/lesion (1.69 vs 1.81; P
      = .48), vessel curvature (0.349 cm(-1) vs 0.345 cm(-1); P = .91) and vessel
      angulation (43.53 degrees  vs 48.45 degrees ; P = .38). The absolute difference
      post- - pre-implantation was similar in lesions without and with TLF, TLR and In
      hospital AMI. The absolute difference post- - pre-implantation was similar with
      both Resolute and Xience in vessel curvature (-0.046 cm(-1) vs -0.047 cm(-1); P =
      .66) and was smaller in number of bends/lesion (-0.08 vs -0.16; P = .13) and in
      vessel angulation (-6.0 degrees  vs -10.1 degrees ; P = .03) with the Resolute.
      CONCLUSIONS: Bended, curved, and angulated lesions and changes in the number of
      bends/lesion, vessel curvature, and angulation from pre to post-implantation have
      no relation with TLF and TLR at 1 year and have no relation with In-hospital AMI
      using second-generation of DES. Resolute appears to be more conformable than
      Xience.

PMID- 22137082
TI  - A randomized study of the effects of exercise training on patients with atrial
      fibrillation.
AB  - BACKGROUND: Exercise training is beneficial in ischemic and congestive heart
      disease. However, the effect on atrial fibrillation (AF) is unknown. METHODS:
      Forty-nine patients with permanent AF (age [mean +/- SD], 70.2 +/- 7.8 years;
      male-to-female ratio, 0.75; body mass index [mean +/- SD], 29.7 +/- 4.3 kg/m(2))
      were randomized to 12-week aerobic exercise training or a control group. Exercise
      capacity, 6-minute walk test (6MWT), cardiac output, quality of life, and
      natriuretic peptides were measured. Cardiac output was measured at rest and
      during ergometer testing, and atrial natriuretic peptide and N-terminal pro-B
      type natriuretic peptide were measured before and after the training period.
      Quality of life was evaluated using the Short-Form 36 and Minnesota Living With
      Heart Failure (MLHF-Q) questionnaires. RESULTS: Improved exercise capacity and
      6MWT were observed in the active patients (P < .001), and at study end, there was
      a significant difference between the active patients and the controls (P = .002).
      Resting pulse decreased in the active patients (94.8 +/- 22.4 to 86.3 +/- 22.5
      beats/min, P = .049) but remained unchanged in the controls. Cardiac output was
      unchanged from baseline to end-of-study period. The MLHF-Q score improved in the
      active group (21.1 +/- 18.0 vs 15.4 +/- 17.5, P = .03). Active patients showed
      progress in 3 of the 8 Short-Form 36 subscales: physical functioning (P = .02),
      general health perceptions (P = .001), and vitality (P = .02). Natriuretic
      peptides were unchanged. CONCLUSION: Twelve weeks of exercise training increased
      exercise capacity and 6MWT and decreased resting pulse rate significantly in
      patients with AF. Overall quality of life increased significantly as measured by
      the cardiology-related MLHF-Q. Cardiac output and natriuretic peptides were
      unchanged in both groups.

PMID- 22137083
TI  - Mutations in the human phospholamban gene in patients with heart failure.
AB  - BACKGROUND: Phospholamban (PLN) is a crucial Ca(2+) cycling protein and a primary
      mediator of the beta-adrenergic effects resulting in enhanced cardiac output.
      Mutations in the gene encoding PLN have been associated with idiopathic dilated
      cardiomyopathy; however, no systematic search for PLN mutations in heart failure
      has been conducted. METHODS: We screened a cohort of 1,014 Brazilian patients
      with heart failure for mutations in the PLN gene. Molecular modeling studies of
      the mutations found were developed. Different disease etiologies were present in
      our sample: idiopathic, ischemic, Chagas, valvular, hypertensive, and others.
      RESULTS: We identified 4 unrelated patients with PLN mutations (prevalence of
      0.4%), 3 of them in the same amino acid residue (R9). Two patients presented a G
      T missense mutation at the G26 nucleotide, which encodes an Arg-Leu substitution
      at codon 9 (R9L). One patient presented a G-A missense mutation at the same
      nucleotide, which encodes an Arg-His substitution at codon 9 (R9H). The fourth
      affected patient presented a T-G nonsense mutation at the nucleotide 116,
      substituting a termination codon for Leu-39 (L39stop). Molecular modeling studies
      suggested that R9L and R9H mutations might affect the region involved in protein
      kinase A docking and probably affect the mechanism modulating the release of
      phosphorylated PLN from the substrate binding site of protein kinase A.
      CONCLUSIONS: Mutations in the PLN gene are a rare cause of heart failure, present
      almost exclusively in patients with dilated cardiomyopathy etiology. The Arg9 and
      Leu39 residues are the leading location of mutations described at this locus to
      date. Despite the few mutated residues described to date, the clinical spectrum
      of presentation appears to vary considerably.

PMID- 22137084
TI  - A trial-based economic evaluation of 2 nurse-led disease management programs in
      heart failure.
AB  - BACKGROUND: Although previously conducted meta-analyses suggest that nurse-led
      disease management programs in heart failure (HF) can improve patient outcomes,
      uncertainty regarding the cost-effectiveness of such programs remains. METHODS:
      To compare the relative merits of 2 variants of a nurse-led disease management
      program (basic or intensive support by a nurse specialized in the management of
      patients with HF) against care as usual (routine follow-up by a cardiologist), a
      trial-based economic evaluation was conducted alongside the COACH study. RESULTS:
      In terms of costs per life-year, basic support was found to dominate care as
      usual, whereas the incremental cost-effectiveness ratio between intensive support
      and basic support was found to be equal to ?532,762 per life-year; in terms of
      costs per quality-adjusted life-year (QALY), basic support was found to dominate
      both care as usual and intensive support. An assessment of the uncertainty
      surrounding these findings showed that, at a threshold value of ?20,000 per life
      year/?20,000 per QALY, basic support was found to have a probability of 69/62% of
      being optimal against 17/30% and 14/8% for care as usual and intensive support,
      respectively. The results of our subgroup analysis suggest that a stratified
      approach based on offering basic support to patients with mild to moderate HF and
      intensive support to patients with severe HF would be optimal if the willingness
      to-pay threshold exceeds ?45,345 per life-year/?59,289 per QALY. CONCLUSIONS:
      Although the differences in costs and effects among the 3 study groups were not
      statistically significant, from a decision-making perspective, basic support
      still had a relatively large probability of generating the highest health
      outcomes at the lowest costs. Our results also substantiated that a stratified
      approach based on offering basic support to patients with mild to moderate HF and
      intensive support to patients with severe HF could further improve health
      outcomes at slightly higher costs.

PMID- 22137085
TI  - Rhinoplasty: current therapy.

PMID- 22137086
TI  - Ectopic pituitary adenoma presenting as a nasopharyngeal mass: CT and MRI
      findings.

PMID- 22137087
TI  - Factors predicting quality of life in a group of Polish subjects with multiple
      sclerosis: accounting for functional state, socio-demographic and clinical
      factors.
AB  - OBJECTIVES: Quality of life (QoL) has presently a firmly established position as
      an important endpoint in medical care. Multiple sclerosis (MS) is a chronic
      neurological disease with considerable effect on patients' QoL. QoL of MS
      patients from many European countries has already been assessed but little is
      known on health-related QoL of Polish subjects with MS. Few studies have taken
      into consideration multiple predictors of QoL. The aim of this study was to
      elicit the most relevant factors that determine QoL of Polish group of MS
      patients. Socio-demographic and clinical factors as well as the influence of
      disability level were analyzed in this study. PATIENTS AND METHODS: 173 MS
      patients and 86 healthy controls underwent assessment using the Mini Mental
      Status Examination, WHOQOL-100, Beck Depression Inventory and Fatigue Severity
      Scale. Data were analyzed by a stepwise linear regression analysis. RESULTS: MS
      patients had significantly worse global QoL and worse QoL in physical and
      psychological health domains, lower level of independence, worse social relations
      and were less satisfied with the surrounding environment they lived in compared
      with healthy controls (p<0.05). MS subjects had also higher level of depression
      and fatigue compared to healthy controls (p<0.05). CONCLUSIONS: The study
      determined that the strongest predictors of global QoL of Polish MS patients were
      depression, disability level and fatigue.

PMID- 22137088
TI  - Effect of superficial collagen patterns and fibrillation of femoral articular
      cartilage on knee joint mechanics-a 3D finite element analysis.
AB  - Collagen fibrils of articular cartilage have specific depth-dependent
      orientations and the fibrils bend in the cartilage surface to exhibit split
      lines. Fibrillation of superficial collagen takes place in osteoarthritis. We
      aimed to investigate the effect of superficial collagen fibril patterns and
      collagen fibrillation of cartilage on stresses and strains within a knee joint. A
      3D finite element model of a knee joint with cartilage and menisci was
      constructed based on magnetic resonance imaging. The fibril-reinforced
      poroviscoelastic material properties with depth-dependent collagen orientations
      and split-line patterns were included in the model. The effects of joint loading
      on stresses and strains in cartilage with various split-line patterns and medial
      collagen fibrillation were simulated under axial impact loading of 1000 N. In the
      model, the collagen fibrils resisted strains along the split-line directions.
      This increased also stresses along the split-lines. On the contrary, contact and
      pore pressures were not affected by split-line patterns. Simulated medial
      osteoarthritis increased tissue strains in both medial and lateral femoral
      condyles, and contact and pore pressures in the lateral femoral condyle. This
      study highlights the importance of the collagen fibril organization, especially
      that indicated by split-line patterns, for the weight-bearing properties of
      articular cartilage. Osteoarthritic changes of cartilage in the medial femoral
      condyle created a possible failure point in the lateral femoral condyle. This
      study provides further evidence on the importance of the collagen fibril
      organization for the optimal function of articular cartilage.

PMID- 22137089
TI  - Estimation of the time-dependent radioactive source-term from the Fukushima
      nuclear power plant accident using atmospheric transport modelling.
AB  - Caesium-137 and Iodine-131 radionuclides released after the Fukushima Dai-ichi
      nuclear power plant accident in March 2011 were detected at monitoring stations
      throughout the world. Using the CTBT radionuclide data and the assumption that
      the Fukushima accident was the only source of these radionuclides, it was
      possible to estimate their time-dependent source-term fourteen days following the
      accident by using atmospheric transport modelling. A reasonable agreement was
      obtained between the modelling results and the estimated radionuclide release
      rates from the Fukushima accident.

PMID- 22137090
TI  - A comparison of verbal communication and psychiatric medication use by Greek and
      Italian residents with dementia in Australian ethno-specific and mainstream aged
      care facilities.
AB  - BACKGROUND: Older migrants with dementia and limited English language proficiency
      in residential care may have unmet needs for social interaction. This project
      compared verbal communication and prescribed psychiatric medication of Greek and
      Italian residents with dementia in ethno-specific and mainstream residential
      care. METHODS: Participants were 82 older Australians of Greek or Italian
      background who had been diagnosed with dementia and were residing in mainstream
      or ethno-specific care. Residents were observed and their language use was
      recorded. An assessment of cognitive impairment was conducted. A structured
      interview was held with a family member and a staff member. RESULTS: The observed
      rate of resident-to-resident communication was higher in the ethno-specific
      facilities. Staff-to-resident interaction rate did not differ between the
      facility types. Residents in ethno-specific care were prescribed antipsychotics
      at a significantly lower rate. CONCLUSIONS: Residents with dementia and limited
      English language proficiency in mainstream care would benefit from greater
      opportunities to interact with peers in their own language. Prescribed medication
      should be monitored to ensure that these residents are not misinterpreted as
      "disruptive," or are not actually more agitated due to difficulty in
      communicating their needs.

PMID- 22137091
TI  - Molecular characteristics of bone marrow mesenchymal stem cells, source of
      regenerative medicine.
AB  - Bone marrow-mesenchymal stem cells (MSCs) are multipotent stem cells capable to
      differentiate into a variety of lineages. MSCs have emerged as reservoirs for
      tissue regeneration and wound healing. Through stress signals, MSCs show great
      tropism for the injured site to manage regenerative process via direct or
      indirect interactions. MSCs avoid the immune rejection, a high quality factor for
      treatment of degenerative diseases. Understanding the molecular mechanisms
      underlying dynamic regulation of various signals, plays an important role for
      future treatment of heart disorders.

PMID- 22137092
TI  - Post-infarction scar coverage using a pericardial-derived vascular adipose flap.
      Pre-clinical results.
AB  - BACKGROUND: Myocardial salvage after coverage with a fat flap was recently
      demonstrated in acute coronary occlusion. The effect of this novel therapeutic
      strategy on a chronic myocardial scar is unknown. METHODS: Myocardial infarction
      (MI) was induced by coil deployment in the mid circumflex artery in the swine
      model. Two weeks after infarction, a pericardial-derived adipose flap was
      transposed, fully covering the scar, in the treated group. Infarct size and
      histopathology were analyzed on post mortem sections. To assess cell migration,
      adenoviral eGFP vectors were injected in the adipose flap and expression was
      evaluated upon sacrifice both at the flap and myocardium. Magnetic resonance
      imaging (MRI) was used to measure left ventricular (LV) ejection fraction and
      ventricular volumes at baseline, 2 weeks post-MI, and at 6 weeks. RESULTS: One
      month after flap transposition, histopathology confirmed a 34% reduction in
      infarct size (8.7% vs. 5.7%; P=0.04) and the presence of vascular connections at
      the flap-myocardium interface. High eGFP expression was detected at the infarct
      core both at the gene and protein level (negligible signal was detected at the
      flap on sacrifice). At the functional level, changes in LV ejection fraction and
      volumes (end-systolic and end-diastolic) were not significantly different between
      groups (all P values>0.1). CONCLUSIONS: Our data support the use of post
      infarction scar coverage with a pericardial-derived fat flap to reduce infarct
      size, due partly to neovascular connections and cell trafficking at the flap
      myocardium interface. Further studies are needed to validate the functional and
      clinical relevance of this intervention.

PMID- 22137093
TI  - Rethinking drinking cultures: a review of drinking cultures and a reconstructed
      dimensional approach.
AB  - OBJECTIVES: This paper presents the synthesis of findings from a literature
      review study of drinking cultures across five West European countries (France,
      Germany, Spain, Sweden and the UK), examining the nature and features of drinking
      typologies before proposing a new dimensional approach. STUDY DESIGN: The study
      incorporated a systematic literature search covering the period 1980-2010 for
      literature from each of the five countries. METHODS: Researchers reviewed
      abstracts and selected relevant material, leading to the inclusion of 203
      articles from database searches plus 26 records from other sources. A summary of
      key findings are presented here. Intercoder reliability checks were performed to
      ensure consistency in inclusion in the review according to pre-ordained selection
      criteria. The review was further supplemented by the inclusion of gray literature
      including policy documents obtained from a range of sources. RESULTS: It was
      found that sociocultural contexts have a major influence on drinking cultures,
      and this is an area in which there have been dramatic changes over the past 30
      years. Differences were found between the countries in terms of drinking
      cultures, the way in which alcohol is viewed, and how alcohol-related policy and
      practice operates. However, there seems to be an increasing homogenization of
      drinking cultures across many countries, strongly influenced by Anglo-US cultural
      zeitgeist. Modern drinking patterns have emerged, offering a complex and often
      overlapping schema of drinking typologies. CONCLUSIONS: The study suggests that
      the wet-dry dichotomy is no longer relevant and that a revised version of a more
      recent dimensional approach featuring three dimensions - hedonism, function and
      control - may be better placed to describe and measure contemporary drinking
      cultures.

PMID- 22137095
TI  - Higher education does not protect against firework-related injuries: a review of
      the economic burden and the risk factors of firework-related injuries in the
      capital of Iran.
AB  - OBJECTIVE: To examine the incidence and risk factors of firework-related injuries
      during the Last Wednesday Eve Festival in Tehran, Iran, with a focus on the
      association of socio-economic status and educational level with the use of
      fireworks and the incidence of firework-related injury. STUDY DESIGN: Cross
      sectional household survey. METHODS: Using a random cluster sampling approach, a
      household survey was conducted in Greater Tehran in April 2008. During a
      structured interview with an adult member of the household, questions were asked
      about the use of fireworks and any firework-related injuries sustained by
      household members during the preceding festival. Data were gathered on
      expenditure on fireworks, medical treatment of firework-related injuries, length
      of hospital stay for the treatment of these injuries, and damage to personal
      property by fireworks. RESULTS: The survey included 2456 households in Greater
      Tehran. At least one member of 18% of these households had used fireworks during
      the Last Wednesday Eve Festival in 2008. The overall incidence of firework
      related injuries was 100 per 100,000 population (95% confidence interval 37-163).
      The use of fireworks was less common among parents and more common among male
      children. Individuals who used fireworks were younger than non-users. Younger age
      and use of fireworks were associated with firework-related injuries (P < 0.05).
      The mean household expenditure on fireworks was US$1.62. Among the households
      that had bought fireworks, the mean expenditure was US$9.40 (standard deviation
      US$16.34). Thirty-two households (1.3%) reported damage to personal property due
      to fireworks during the festival costing US$3.30-167.20. The regional price of
      housing in the study area was correlated with the educational level of the head
      of the household. Higher educational level of the head of the household was
      associated with participation in firework activities by household members,
      expenditure on fireworks, and the amount of financial loss due to fireworks (all
      P < 0.05). CONCLUSION: Fireworks are associated with serious injuries, and impose
      a non-trivial financial burden on families. While personal use of fireworks was
      an independent risk factor for firework-related injuries, higher socio-economic
      status of the household and higher educational level of the head of the household
      were not protective factors.

PMID- 22137096
TI  - Increase in reported adverse events following seasonal influenza vaccination
      among the French armed forces, 2008-2009: possible role of stimulated reporting
      and background cases of influenza-like infection.
AB  - OBJECTIVES: In September 2009, an increase in seasonal influenza vaccine adverse
      events (VAE), compared with reports for previous years, was detected among the
      French armed forces in the setting of an extended immunization campaign. This
      work presents the results of this investigation. STUDY DESIGN: VAE were surveyed
      among all French military personnel from 2008 to 2009 by Epidemiological
      Departments of the French Military Health Service. For each case, a notification
      form was completed, providing patient and clinical information. METHODS: Case
      definitions were derived from the French drug vigilance guidelines. Three types
      of VAE were considered: non-serious, serious and unexpected. Incidence rates were
      calculated by relating VAE to the number of vaccine doses injected. RESULTS:
      Forty-seven seasonal influenza VAE were reported in continental France: 18 in
      2008 and 29 in 2009. The annual reporting rate was higher in 2009 (31.6 vs 16.6
      VAE per 100,000 injections, respectively). The highest monthly incidence was
      observed in September 2009 (60.8 events per 100,000 injections). Two other peaks
      were observed in February 2008 and March 2009. The incidence in September 2009
      was not significantly different from the incidences in February 2008 and March
      2009. It was observed that incidence peaks occurred during influenza epidemic
      periods. One serious neurological VAE was observed. CONCLUSIONS: The increase in
      seasonal influenza VAE in late 2009 mainly involved non-serious events, and could
      reflect stimulated reporting in the context of the A(H1N1)pdm09 pandemic. VAE
      reporting rates were highest during influenza epidemic periods, which could be
      explained by VAE being wrongly attributed to the vaccine when symptoms could
      reflect coincident background cases of viral infection.

PMID- 22137094
TI  - Risk factors for injury in a national cohort of 87,134 Thai adults.
AB  - BACKGROUND: Information is needed regarding risk factors associated with injury.
      In middle- and lower-income countries, injury studies have focused on road
      traffic injuries and less attention has been given to other types of injuries.
      METHODS: This study is part of overarching health-risk transition research in
      Thailand with a large national cohort study that began in 2005 (n = 87,134).
      Associations between potential determinants and overall injury were measured, as
      well as injury by location (transport, home, work and sport), using data gathered
      from the baseline questionnaire. RESULTS: In total, 21.5% of the cohort reported
      at least one incidence of injury over the last 12 months. Risk factors associated
      with injury were being male [odds ratio (OR) 1.20], having lower income (OR
      1.70), having problems with vision (OR 1.46), having epilepsy (OR 3.02), having
      depression/anxiety (OR 1.62), poor self-assessed health (OR 1.68), being obese
      (OR 1.24) and death of father due to injury (OR 1.59). Analysis of injury by
      location provided more specific information on risk factors. For example, females
      were more likely to report injuries at home, while males, urban residents and
      regular alcohol drinkers were more likely to report transport injuries.
      CONCLUSIONS: The risk of injury in Thailand varies considerably by location,
      sociodemographic group and several categories of co-existing morbidities. Such
      epidemiological information identifying risk factors for injury is useful for
      designing targeted injury prevention programmes in Thailand and other middle
      income countries.

PMID- 22137097
TI  - Needle track seeding after percutaneous microwave ablation of malignant liver
      tumors under ultrasound guidance: analysis of 14-year experience with 1462
      patients at a single center.
AB  - OBJECTIVE: To determine the incidence and risk factors associated with needle
      tract seeding after percutaneous microwave ablation (MWA) of liver cancer under
      ultrasound guidance. MATERIALS AND METHODS: Over a 14-year period, a total of
      1462 patients with 2530 malignant nodules were treated by MWA. The influence of
      age, sex, Child-pugh classification, tumor size, tumor position, previous biopsy,
      insertion number and antenna type on the risk of neoplastic seeding was assessed.
      The survival of seeding patients after the MWA was analyzed. RESULTS: Eleven
      patients with 12 nodules (0.47% per tumor, 0.75% per patient) were identified
      with needle tract seeding with an interval time of 6-37 (median 10) months after
      MWA. The mean size of the seeding nodule was 2.3 +/- 0.7 cm (from 1.3 to 3.9 cm).
      Only previous biopsy was significantly associated with neoplastic seeding
      (P=0.02). All the seeding lesions were successfully treated by resection, MWA,
      radiation or high intensity focus ultrasound. The median survival period of the
      11 patients after the MWA was 36.0 months. The cumulative survival rates of the
      11 patients after the MWA at 1-, 2-, 3-, 4- and 5-year were 90.9%, 72.7%, 62.3%,
      31.2% and 15.6%, respectively. CONCLUSION: The results showed that the neoplastic
      seeding was a low risk complication of percutaneous MWA of liver cancer and was
      considered acceptable in general.

PMID- 22137098
TI  - Man to man training: can it help improve the diagnostic performances and
      interobserver variabilities of thyroid ultrasonography in residents?
AB  - OBJECTIVE: The purpose of this study was to determine whether the man to man
      training can improve the diagnostic performances and interobserver variabilities
      of residents on thyroid ultrasonography. MATERIALS AND METHODS: A set of 80 quiz
      cases with ultrasonography images of thyroid nodules (40 benign and 40 malignant
      on histopathology) were shown to the residents. Residents 1, 2, and 3 had not
      received the man to man training while Residents 4, 5, 6, and 7 had. The seven
      residents were asked to fill out one of the ultrasonography features (internal
      composition, echogenicity, margin, calcification, and shape) and the final
      assessment (probably benign and suspicious). Thyroid nodules with one or more
      ultrasonography features including marked hypoechogenicity, microlobulated or
      irregular margins, microcalcifications, and taller than wide shape were assessed
      as suspicious nodules. The diagnostic performances of US by the seven residents
      and interobserver variabilities between the seven residents and a faculty
      radiologist were calculated. RESULTS: The sensitivities, negative predictive
      values, and accuracies of Residents 4, 5, 6, and 7 were higher than those of
      Residents 1, 2, and 3. The final assessment between Residents 4, 5, 6, and 7 and
      the faculty radiologist showed almost perfect agreement but that between
      Residents 1, 2, and 3 and the faculty radiologist showed substantial agreement.
      CONCLUSION: The man to man training is crucial for the residents to show better
      diagnostic performances and improvement of interobserver variabilities for
      evaluating thyroid nodules with ultrasonography.

PMID- 22137100
TI  - Just follow your nose: homing by olfactory cues in ants.
AB  - How is an ant-equipped with a brain that barely exceeds the size of a pinhead
      capable of achieving navigational marvels? Even though evidences suggest that
      navigation is a multimodal process, ants heavily depend on olfactory cues-of
      pheromonal and non-pheromonal nature-for foraging and orientation. Recent studies
      have directed their attention to the efficiency of pheromone trail networks.
      Advances in neurophysiological techniques make it possible to investigate trail
      pheromone processing in the ant's brain. In addition to relying on pheromone
      odours, ants also make use of volatiles emanating from the nest surroundings.
      Deposited in the vicinity of the nest, these home-range markings help the ants to
      home after a foraging run. Furthermore, olfactory landmarks associated with the
      nest enhance ants' homing abilities.

PMID- 22137099
TI  - Finding disease variants in Mendelian disorders by using sequence data: methods
      and applications.
AB  - Many sequencing studies are now underway to identify the genetic causes for both
      Mendelian and complex traits. Via exome-sequencing, genes harboring variants
      implicated in several Mendelian traits have already been identified. The
      underlying methodology in these studies is a multistep algorithm based on
      filtering variants identified in a small number of affected individuals and
      depends on whether they are novel (not yet seen in public resources such as
      dbSNP), shared among affected individuals, and other external functional
      information on the variants. Although intuitive, these filter-based methods are
      nonoptimal and do not provide any measure of statistical uncertainty. We describe
      here a formal statistical approach that has several distinct advantages: (1) it
      provides fast computation of approximate p values for individual genes, (2) it
      adjusts for the background variation in each gene, (3) it allows for
      incorporation of functional or linkage-based information, and (4) it accommodates
      designs based on both affected relative pairs and unrelated affected individuals.
      We show via simulations that the proposed approach can be used in conjunction
      with the existing filter-based methods to achieve a substantially better ranking
      of a gene relevant for disease when compared to currently used filter-based
      approaches, this is especially so in the presence of disease locus heterogeneity.
      We revisit recent studies on three Mendelian diseases and show that the proposed
      approach results in the implicated gene being ranked first in all studies, and
      approximate p values of 10(-6) for the Miller Syndrome gene, 1.0 * 10(-4) for the
      Freeman-Sheldon Syndrome gene, and 3.5 * 10(-5) for the Kabuki Syndrome gene.

PMID- 22137101
TI  - Humans seem to produce arsenobetaine and dimethylarsinate after a bolus dose of
      seafood.
AB  - Seafood is the predominant food source of several organoarsenic compounds. Some
      seafood species, like crustaceans and seaweed, also contain inorganic arsenic
      (iAs), a well-known toxicant. It is unclear whether human biotransformation of
      ingested organoarsenicals from seafood result in formation of arsenicals of
      health concern. The present controlled dietary study examined the urinary
      excretion of arsenic compounds (total arsenic (tAs), iAs, AB (arsenobetaine),
      dimethylarsinate (DMA) and methylarsonate (MA)) following ingestion of a single
      test meal of seafood (cod, 780 MUg tAs, farmed salmon, 290 MUg tAs or blue
      mussel, 690 MUg tAs or potato (control, 110 MUg tAs)) in 38 volunteers. The
      amount of ingested tAs excreted via the urine within 0-72 h varied significantly
      among the groups: Cod, 74% (52-92%), salmon 56% (46-82%), blue mussel 49% (37
      78%), control 45% (30-60%). The estimated total urinary excretion of AB was
      higher than the amount of ingested AB in the blue mussel group (112%) and also
      ingestion of cod seemed to result in more AB, indicating possible endogenous
      formation of AB from other organoarsenicals. Excretion of iAs was lower than
      ingested (13-22% of the ingested iAs was excreted in the different groups).
      Although the ingested amount of iAs+DMA+MA was low for all seafood groups (1.2
      4.5% of tAs ingested), the urinary DMA excretion was high in the blue mussel and
      salmon groups, counting for 25% and 11% of the excreted tAs respectively. In
      conclusion our data indicate a possible formation of AB as a result of
      biotransformation of other organic arsenicals. The considerable amount of DMA
      excreted is probably not only due to methylation of ingested iAs, but due to
      biotransformation of organoarsenicals making it an inappropriate biomarker of iAs
      exposure in populations with a high seafood intake.

PMID- 22137102
TI  - Silica-metal core-shell nanostructures.
AB  - Silica-metal nanostructures consisting of silica cores and metal nanoshells
      attract a lot of attention because of their unique properties and potential
      applications ranging from catalysis and biosensing to optical devices and
      medicine. The important feature of these nanostructures is the possibility of
      controlling their properties by the variation of their geometry, shell morphology
      and shell material. This review is devoted to silica-noble metal core-shell
      nanostructures; specifically, it outlines the main methods used for the
      preparation and surface modification of silica particles and presents the major
      strategies for the formation of metal nanoshells on the modified silica
      particles. A special emphasis is given to the Stober method, which is relatively
      simple, effective and well verified for the synthesis of large and highly uniform
      silica particles (with diameters from 100 nm to a few microns). Next, the surface
      chemistry of these particles is discussed with a special focus on the attachment
      of specific organic groups such as aminopropyl or mercaptopropyl groups, which
      interact strongly with metal species. Finally, the synthesis, characterization
      and application of various silica-metal core-shell nanostructures are reviewed,
      especially in relation to the siliceous cores with gold or silver nanoshells.
      Nowadays, gold is most often used metal for the formation of nanoshells due to
      its beneficial properties for many applications. However, other metals such as
      silver, platinum, palladium, nickel and copper were also used for fabrication of
      core-shell nanostructures. Silica-metal nanostructures can be prepared using
      various methods, for instance, (i) growth of metal nanoshells on the siliceous
      cores with deposited metal nanoparticles, (ii) reduction of metal species
      accompanied by precipitation of metal nanoparticles on the modified silica cores,
      and (iii) formation of metal nanoshells under ultrasonic conditions. A special
      emphasis is given to the seed-mediated growth, where metal nanoshells are formed
      on the modified silica cores with deposited metal nanoparticles. This strategy
      assures a good control of the nanoshell thickness as well as its surface
      properties.

PMID- 22137103
TI  - The temporal relationship between growth hormone and slow wave sleep is weaker
      after menopause.
AB  - OBJECTIVE: To study the temporal association between growth hormone (GH) and slow
      wave sleep (SWS) in middle-aged women. METHODS: Seventeen premenopausal and 18
      postmenopausal women were studied using all-night polygraphic sleep recordings
      and blood sampling at 20-min intervals. The postmenopausal women were re-studied
      after six months on hormone therapy (HT) according to a randomized, double-blind,
      placebo-controlled protocol. RESULTS: The total sleep time (premenopausal 361.9+/
      81.5 min, postmenopausal 358+/-67.7 min) and the percentages of the sleep stages
      did not differ between pre- and postmenopausal women. In postmenopausal women the
      first GH peak after sleep onset occurred later and with a more variable time
      interval compared to premenopausal women. The percentage of SWS was highest 40-20
      min prior to the first GH peak after sleep onset in both groups with a higher SWS
      proportion in premenopausal women (p=0.048), although the total SWS percent for
      night did not differ. HT did not affect the distribution of SWS in postmenopausal
      women. CONCLUSIONS: The temporal relationship between GH and SWS in premenopausal
      women is less robust after menopause and is not improved with HT.

PMID- 22137104
TI  - Desaturation during sleep in mild to moderate COPD: a marker of poor sleep
      quality alone?

PMID- 22137105
TI  - Young-onset REM sleep behavior disorder: Beyond the antidepressant effect.

PMID- 22137106
TI  - Hypoxemia and cardiovascular disease in COPD. Not related to sleep disordered
      breathing after all.

PMID- 22137107
TI  - Dehydration during sleep affects cognitive performance.

PMID- 22137108
TI  - Helicobacter pylori may play a role in both obstructive sleep apnea and metabolic
      syndrome.

PMID- 22137109
TI  - Quality of life in patients with narcolepsy with cataplexy, narcolepsy without
      cataplexy, and idiopathic hypersomnia without long sleep time: comparison between
      patients on psychostimulants, drug-naive patients and the general Japanese
      population.
AB  - OBJECTIVE: To assess the quality of life of patients with narcolepsy with
      cataplexy (NA-CA), narcolepsy without cataplexy (NA w/o CA), and idiopathic
      hypersomnia without long sleep time (IHS w/o LST) who were taking psychostimulant
      medication, and to ascertain which factors (including psychosocial and
      environmental variables) influence quality of life in this population. METHODS:
      In total, 185 patients who had received regular treatment were enrolled in the
      study (NA-CA, n=83; NA w/o CA, n=48; IHS w/o LST, n=54). Patients were asked to
      complete questionnaires including the Short Form-36 Health Survey (SF-36), the
      Epworth Sleepiness Scale (ESS), and items concerning psychosocial and
      environmental variables. RESULTS: All three diagnostic groups had significantly
      lower scores for most SF-36 domains compared with the Japanese normative data,
      and the ESS score was significantly reduced with treatment. Multiple logistic
      regression analyses revealed that several SF-36 domains were associated with the
      ESS score; autonomy in controlling own job schedule, experience of divorce or
      break up with a partner due to symptoms, experience of being forced to relocate
      or being dismissed due to symptoms, and perception of support from others.
      CONCLUSIONS: The severity of subjective sleepiness and psychological and
      environmental variables influenced quality of life in patients with these
      hypersomnias of central origin.

PMID- 22137110
TI  - Sleep induced abnormal motor behaviors caused by medium-chain acyl-CoA
      dehydrogenase deficiency: a case report.

PMID- 22137111
TI  - Sleep duration pattern and chronic diseases in Brazilian adults (ISACAMP,
      2008/09).
AB  - OBJECTIVE: The aim of the present study was to assess sleep patterns in the adult
      population of the city of Campinas (Brazil) according to
      socioeconomic/demographic variables, chronic diseases, and symptoms. METHODS: A
      population-based cross-sectional study was conducted using data from the Campinas
      Health Survey (ISACAMP) carried out in 2008 and 2009. A total of 2637 individuals
      aged 18 years or older (obtained from a probabilistic sample) were analyzed.
      Associations between sleep pattern and the independent variables were determined
      using the chi-square test. Multinomial logistic regression models were used to
      adjust for confounders. RESULTS: The prevalence of six or fewer hours of sleep
      was greater among individuals aged 40 years or older and among divorced or single
      individuals. The sleep pattern of nine or more hours was more prevalent among
      those with less than 40 years of age, among those who were divorced, or single,
      among those with a lower level of schooling, those who did not work and
      housewives. Both short and long sleep patterns were more prevalent among
      individuals with heart disease, vascular problems,
      rheumatism/arthritis/arthrosis, osteoporosis, or emotional problems. The
      prevalence of the short sleep duration was greater among individuals with back
      problems and those with three or more health conditions. A strong association was
      found between sleep duration and sleep quality. CONCLUSIONS: Socio-demographic
      factors and health diseases were associated to sleep duration. This issue should
      be considered in health promotion strategies.

PMID- 22137112
TI  - In the fight against advanced glycation end-products (AGEs), you should treat
      OSA, shouldn't you?

PMID- 22137114
TI  - Diagnostic accuracy of a structured interview for nocturnal frontal lobe epilepsy
      (SINFLE): a proposal for developing diagnostic criteria.
AB  - OBJECTIVES: To measure the accuracy of anamnestic features collected during
      clinical history for the diagnosis of nocturnal frontal lobe epilepsy (NFLE).
      METHODS: A case-control diagnostic study. Participants included a case group of
      people with ascertained target disease (NFLE group) and a control group of people
      with sleep disorders potentially confounding for NFLS (NOT-NFLE group), defined
      by means of a consensus procedure among experts (panel diagnosis as reference
      standard). Two major clinical patterns defining the semeiology of the epileptic
      event (i.e. dystonic, DP, and/or hyperkinetic pattern, HP), and 13 additional
      minor features were identified, formulated as questions, and telephonically
      administered to NFLE and NOT-NFLE groups by a trained doctor blinded to the final
      diagnosis. The diagnostic accuracy of each characteristic was tested against the
      reference standard. RESULTS: Out of 262 selected subjects, 101 were recruited; 42
      were NFLE and 59 NOT-NFLE. A positive history of DP or HP had a sensitivity of
      59.5% and a specificity of 91.5%, irrespective of the other minor anamnestic
      features. The anamnestic model improved, with a sensitivity of 59.5% and
      specificity of 96.6%, if at least one of the following four minor anamnestic
      features was added: (a) duration less than two minutes, (b) unstructured
      vocalization during the episode, (c) experience of an aura preceding the motor
      attack, and (d) a history of tonic-clonic seizures during sleep. CONCLUSIONS: The
      present study disclosed two major anamnestic patterns and four minor features
      that we called SINFLE, with unsatisfactory sensitivity but high specificity.
      These patterns could be the basis for developing future NFLE diagnostic criteria
      and to quantify the diagnostic accuracy of elements usually collected in the
      clinical history.

PMID- 22137115
TI  - What is cause and what is effect?

PMID- 22137116
TI  - Increased serum levels of advanced glycation end-products is associated with
      severity of sleep disordered breathing but not insulin sensitivity in non
      diabetic men with obstructive sleep apnoea.
AB  - BACKGROUND: Patients with diabetes mellitus are known to have increased serum
      levels of advanced glycation end-products (AGEs), and this is also associated
      with insulin resistance. This study aimed to investigate the relationship between
      serum AGEs and insulin sensitivity in non-diabetic subjects with obstructive
      sleep apnoea (OSA). METHODS: Adult males with no known comorbidities were
      recruited from the sleep clinic of a university teaching hospital. They underwent
      overnight in-laboratory polysomnography. Fasting blood was taken to measure serum
      AGE and plasma glucose levels. Insulin sensitivity was estimated using the short
      insulin tolerance test. RESULTS: In total, 105 subjects with a mean age of 43.5
      (standard deviation [SD] 9.2)years, mean body mass index of 27.1 (SD 4.0)kg/m(2),
      and median apnoea-hypopnoea index (AHI) of 17 (interquartile range 5-46) were
      analysed. Serum AGE levels were significantly higher in subjects with OSA (AHI
      >=5), compared with those without OSA (AHI <5) (3.9 [SD 1.2] vs. 3.2 [SD
      0.8]MUg/ml, respectively; P=0.037) after adjusting for confounders. AGE levels
      were positively correlated with AHI (r=0.318, P=0.001), but not with insulin
      sensitivity. AGE levels decreased in subjects with moderate-to-severe OSA who
      received continuous positive airway pressure (CPAP) treatment for three months
      (n=18, P=0.017). CONCLUSIONS: Serum AGE levels correlate with AHI in non-diabetic
      adult males. This relationship cannot be explained by insulin sensitivity.
      Supporting the hypothesis of a direct relationship between AHI and AGEs, AGE
      levels were found to decline with CPAP therapy.

PMID- 22137117
TI  - Sleep in the critically ill: an epoch adventure.

PMID- 22137118
TI  - Infant sleep and early parental sleep-related cognitions predict sleep in pre
      school children.
AB  - OBJECTIVE: To investigate early predictors of sleep patterns in pre-school age
      children. Specifically, we were interested in exploring whether infant sleep
      patterns and parenting factors assessed at 12 months would predict sleep in four
      year-old children. METHODS: This was a follow-up study of a home-based
      longitudinal study, exploring the links between parental cognitions and
      children's sleep. The present study included 71 families (boys 58%) and focused
      on data collected when children were 12 months and four years old. Sleep at both
      time points was assessed for four weekdays by actigraphy and parental reports.
      RESULTS: Statistically significant zero-order correlations were found between
      early sleep patterns, maternal cognitions, and soothing behaviors at 12 months,
      and sleep patterns at four years. Multiple regression analysis revealed that 12
      months maternal cognitions reflecting difficulties with limiting parental
      nighttime involvement were a statistically significant predictor of fragmented
      child's sleep and of parental bedtime involvement at four years. More objective
      infant night-wakings at 12 months predicted lower sleep efficiency at four years.
      CONCLUSIONS: Both early sleep patterns and maternal sleep-related cognitions
      during infancy are significant predictors of sleep quality of pre-school
      children. These findings are clinically meaningful as they suggest that improving
      infant sleep and addressing early parental beliefs and perceptions regarding
      infant sleep may help in preventing sleep problems of pre-school children.

PMID- 22137119
TI  - Efficacy and safety of pramipexole in chinese patients with restless legs
      syndrome: results from a multi-center, randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: We performed a six-week study of pramipexole vs. a placebo in Chinese
      restless legs syndrome patients. METHODS: Overall, 305 enrolled patients were
      assigned randomly in a 2:1 ratio to the pramipexole group (N=202) and the placebo
      group (N=103). RESULTS: Of 287 patients in the full analysis set, the pramipexole
      group showed significant improvement compared with the placebo group in the
      change of their International Restless Legs Syndrome Study Group Rating Scale of
      Severity (IRLS) total score from baseline to week 6 after adjustment of centers
      and baseline characters (-15.87+/-0.66 vs. -11.35+/-0.92, p<0.0001) and in the
      proportion of patients who were "much improved" and "very much improved" when
      measured by Clinical Global Impressions-Improvement (81.9% vs. 54.3%, p<0.0001).
      At week 6, the IRLS responder rate was 73.8% (pramipexole) and 48.9% (placebo)
      (p<0.0001) and the patient global impression responder rate was 68.6%
      (pramipexole) and 43.5% (placebo) (p<0.0001). The proportion of adverse events
      was 62.9% in the pramipexole group and 43.7% in the placebo group, respectively.
      No deaths occurred. CONCLUSION: Pramipexole was effective and well-tolerated in
      Chinese patients with restless legs syndrome.

PMID- 22137120
TI  - Interferon gamma induces actin polymerization, Rac1 activation and down regulates
      phagocytosis in human monocytic cells.
AB  - IFNgamma is a potent activator and IL-10 a powerful inhibitor of macrophage
      functions. However, neither all cellular functions are enhanced by IFNgamma nor
      IL-10 inhibits all cellular responses. Thus, FcgammaRs-mediated phagocytosis in
      monocyte-derived macrophages (MDM) increases after IL-10 treatment, and decreases
      after treatment with IFNgamma, although both IL-10 and IFNgamma up regulate
      FcgammaRI expression. In this work we investigated the effect of IFNgamma and IL
      10 on phagocytic signaling by FcgammaRs in MDM. Treatment with IFNgamma
      diminished phagocytosis of IgG-opsonized SRBC (IgG-SRBC) while treatment with IL
      10 increased it. These opposite effects cannot be attributed to changes in
      FcgammaR expression induced by each cytokine. Early biochemical responses
      mediated by FcgammaRs were distinctly affected by cytokine treatment. Syk
      phosphorylation and the rise in [Ca(2+)](i) were higher after IL-10 treatment,
      whereas IFNgamma treatment also increased Syk phosphorylation but had no effect
      on the rise in [Ca(2+)](i). IFNgamma treatment led to increased basal levels of F
      actin and this effect correlated with the decrease in phagocytosis of both IgG
      SRBC and non-opsonized Escherichia coli. IL-10 did not alter F-actin basal
      levels, and enhanced the phagocytosis of E. coli and IgG-SRBC. The level of F
      actin reached after IFNgamma treatment was not further increased after
      stimulation with IgG-SRBC or CCL5, whereas MDM treated with IL-10 showed a
      slightly higher response than control cells to CCL5. IFNgamma increased Rac1-GTP
      levels. Inhibition of PI3K with LY294002 prevented IFNgamma-mediated actin
      polymerization. Our data suggest that IFNgamma induces a higher basal level of F
      actin and activation of Rac1, affecting the response to stimuli that induce
      cytoskeleton rearrangement such as phagocytic or chemotactic stimuli.

PMID- 22137121
TI  - Interpretation of elevated plasma visfatin concentrations in patients with ST
      elevation myocardial infarction.
AB  - Visfatin is a cytokine that is expressed in many tissues, including the heart,
      and has been proposed to play a role in plaque destabilization leading to acute
      myocardial injury. The present study evaluates plasma levels of visfatin in acute
      ST-elevation myocardial infarction (STEMI) patients and examines the temporal
      changes in visfatin levels from the acute period to the subacute period to
      determine a correlation with the degree of myocardial ischemia. We evaluated 54
      patients with STEMI. Circulating levels of visfatin and brain natriuretic peptide
      (BNP) were measured by ELISA. In addition, local expression of visfatin and BNP
      were detected by quantitative real-time polymerase chain reaction and
      immunohistochemical (IHC) analysis of left ventricular myocytes in a mouse model
      of myocardial infarction (MI). Plasma levels of visfatin were significantly
      increased in patients with STEMI on admission, relative to controls (effort
      angina patients and individuals without coronary artery disease). The visfatin
      levels reached a peak 24h after percutaneous coronary intervention (PCI) and then
      decreased toward the control range during the first week after PCI. The basal
      plasma visfatin levels were found to correlate with peak troponin-I, peak
      creatine kinase-MB, total white blood cell count, and BNP levels. Trend analyses
      confirmed that visfatin levels correlated with the number of diseased coronary
      arteries. Further, in MI mice, mRNA levels of visfatin and BNP were found to be
      higher than in sham-treated mice. IHC analysis showed that visfatin and BNP
      immunoreactivity was diffusely observable in left ventricular myocytes of the MI
      mice. This study indicates that plasma visfatin levels are significantly higher
      in STEMI patients and that these higher visfatin levels correlate with elevated
      levels of cardiac enzymes, suggesting that increased plasma visfatin may be
      closely related to the degree of myocardial damage.

PMID- 22137122
TI  - Paraneoplastic syndrome in mice bearing high-angiogenic variant of Lewis lung
      carcinoma: relations with tumor derived VEGF.
AB  - BACKGROUND: It is well-known that tumor exerts nonmetastatic systemic effect on
      organism caused the development of paraneoplastic syndrome (PNS). Recent findings
      point to relationships between development of PNS and tumor-derived vascular
      endothelial growth factor (VEGF). AIM: Comparative study of PNS manifestations in
      mice with transplanted two variants of Lewis lung carcinoma with different
      angiogenic potential. METHODS: Plasma VEGF level was determined by immunoenzyme
      method, hematological indices were estimated with the use of hematological
      analyzer, the weight and cellularity of spleen and thymus were registered and
      histological analysis of tissue section of these organs was performed. RESULTS:
      Manifestations of anemia, extramedullary hemopoiesis and tumor-associated
      inflammatory disease was observed in animals with high angiogenic LLC/R9 variant
      and was not registered in low angiogenic LLC. The emergence of PNS symptoms
      correlated with elevated level of circulating VEGF at the early stages of LLC/R9
      growth. CONCLUSION: Manifestation of the paraneoplastic hematological syndrome
      most likely is conditioned on the ability of cancer cell to secrete VEGF in a
      high rate.

PMID- 22137123
TI  - Controllable synthesis of monodispersed silver nanoparticles as standards for
      quantitative assessment of their cytotoxicity.
AB  - Silver nanoparticles (Ag NPs) are appealing due to their excellent
      antibacterial/antivirus properties. At the meantime, the wide applications of Ag
      NPs as antibacterial/antivirus agents arise the concern of Ag NPs' toxicity.
      However, quantitative understanding of the cytotoxicity of Ag NPs is minimum
      since that the Ag NPs in current studies have wide size distributions, in which
      the size effect of Ag NPs on cytotoxicity was unable to be accurately evaluated.
      In this work, unprecedentedly monodispersed Ag NPs with sizes of 25, 35, 45, 60
      and 70 nm were obtained, respectively, by using an optimized polyol method with
      poly(vinyl pyrrolidone) (PVP) as surfactant. It was found that the reaction
      temperature, reaction time, concentration of the surfactant and reactants are
      playing important roles in determining the size and size distribution of Ag NPs.
      With the monodispersed Ag NPs as standard samples, the size- and dose- dependent
      cytotoxicity of Ag NPs against Human lung fibroblast (HLF) cells was accurately
      accomplished in terms of cell viability, apoptosis and necrosis, reactive oxygen
      species, etc. We expect that the monodispersed Ag NPs will act as the standard
      samples for quantitatively characterizing the toxicity of Ag NPs in vitro and in
      vivo.

PMID- 22137124
TI  - Plasmonic nanobubble-enhanced endosomal escape processes for selective and guided
      intracellular delivery of chemotherapy to drug-resistant cancer cells.
AB  - Cancer chemotherapies suffer from multi drug resistance, high non-specific
      toxicity and heterogeneity of tumors. We report a method of plasmonic nanobubble
      enhanced endosomal escape (PNBEE) for the selective, fast and guided
      intracellular delivery of drugs through a self-assembly by cancer cells of
      separately targeted gold nanoparticles and encapsulated drug (Doxil). The co
      localized with Doxil plasmonic nanobubbles optically generated in cancer cells
      released the drug into the cytoplasm thus increasing the therapeutic efficacy
      against these drug-resistant cells by 31-fold, reducing drug dose by 20-fold, the
      treatment time by 3-fold and the non-specific toxicity by 10-fold compared to
      standard treatment. Thus the PNBEE mechanism provided selective, safe and
      efficient intracellular drug delivery in heterogeneous environment opening new
      opportunities for drug therapies.

PMID- 22137125
TI  - The use of cholesterol-containing biodegradable block copolymers to exploit
      hydrophobic interactions for the delivery of anticancer drugs.
AB  - A series of biodegradable amphiphilic block copolymers with controlled
      composition and relatively low polydispersity index were synthesized from
      monomethoxy polyethylene glycol (mPEG-OH, 5 kDa) via organocatalytic ring opening
      polymerization of aliphatic cyclic carbonate monomers - trimethylene carbonate
      (TMC) or cholesteryl 2-(5-methyl-2-oxo-1,3-dioxane-5-carboxyloyloxy)ethyl
      carbamate (MTC-Chol) or a copolymer of both the monomers (TMC and MTC-Chol):
      mPEG(113)-b-PTMC(67), mPEG(113)-b-P(MTC-Chol(11)) and mPEG(113)-b-P(MTC-Chol(x)
      co-TMC(y))(x+y). These well-defined polymers were employed to study the role of
      molecular weight and composition of the hydrophobic block of the polymers in
      loading paclitaxel (PTX), an extremely hydrophobic anticancer drug with rigid
      structure and strong tendency of self-association to form long fibers. The PTX
      loaded micelles were fabricated by simple self-assembly without sonication or
      homogenization procedures. The results demonstrated that the presence of both MTC
      Chol and TMC in the hydrophobic block significantly increased PTX loading levels,
      and the micelles formed from the polymer with the optimized composition (i.e.
      mPEG(113)-b-P(MTC-Chol(11)-co-TMC(30))) were in nanosize (36 nm) with narrow size
      distribution (PDI: 0.07) and high PTX loading capacity (15 wt.%). In vitro
      treatment of human liver hepatocellular carcinoma HepG2 cells with blank micelles
      showed that these polymeric carriers were non-cytotoxic with cell viability
      greater than 90% at ~2400 mg/L. Importantly, PTX-loaded micelles were able to
      kill cancer cells much more effectively compared to free PTX. In addition, these
      nanocarriers also possessed exceptional kinetic stability. The results from non
      invasive near-infrared fluorescence (NIRF) imaging studies showed that these
      micelles allowed effective passive targeting, and were preferably accumulated in
      tumor tissue with limited distribution to healthy organs.

PMID- 22137126
TI  - Consequences of ineffective decellularization of biologic scaffolds on the host
      response.
AB  - Biologic scaffold materials composed of extracellular matrix (ECM) are routinely
      used for a variety of clinical applications. Despite known variations in tissue
      remodeling outcomes, quantitative criteria by which decellularization can be
      assessed were only recently described and as a result, the amount of retained
      cellular material varies widely among commercial products. The objective of this
      study was to evaluate the consequences of ineffective decellularization on the
      host response. Three different methods of decellularization were used to
      decellularize porcine small intestinal ECM (SIS-ECM). The amount of cell remnants
      was quantified by the amount and fragmentation of DNA within the scaffold
      materials. The M1/M2 phenotypic polarization profile of macrophages, activated in
      response to these ECM scaffolds, was assessed in vitro and in vivo using a rodent
      model of body wall repair. The results show that, in vitro, more aggressive
      decellularization is associated with a shift in macrophage phenotype predominance
      from M1 to M2. While this shift was not quantitatively apparent in vivo, notable
      differences were found in the distribution of M1 vs. M2 macrophages within the
      various scaffolds. A clear association between macrophage phenotype and
      remodeling outcome exists and effective decellularization remains an important
      component in the processing of ECM-based scaffolds.

PMID- 22137127
TI  - Single walled carbon nanotubes as drug delivery vehicles: targeting doxorubicin
      to tumors.
AB  - Single walled carbon nanotubes (SWNTs) are emerging as promising delivery
      vehicles for cancer diagnostics and chemotherapies due to their unique
      properties, including, remarkable cell membrane penetrability, high drug-carrying
      capacities, pH-dependent therapeutic unloading, prolonged circulating times and
      intrinsic fluorescent, photothermal, photoacoustic and Raman properties. In this
      leading opinion paper, we systemically discuss and evaluate the relationship of
      the biological safety of SWNTs with their physicochemical properties such as
      their length, purity, agglomeration state, concentration and surface
      functionalization. Other relevant issues, including the cellular uptake
      mechanism, biodistribution and metabolism of SWNTs are also reviewed. The design
      and preparation of SWNT-based drug delivery systems (DDSs) and their
      pharmacokinetic, cancer targeting and therapeutic properties both in vitro and in
      vivo are highlighted. Future opportunities and challenges of SWNT-based DDSs are
      also discussed.

PMID- 22137128
TI  - Editorial on "Mass transfer kinetics, band broadening and column efficiency" by
      F. Gritti and G. Guiochon.

PMID- 22137129
TI  - Critical overview of selected contemporary sample preparation techniques.
AB  - Sample preparation procedures in use in many application areas are still tedious
      and manually intensive protocols. These characteristics mean that sample
      treatment is considered the most time-consuming and error-prone part of the
      analytical scheme. The increasing demand for faster, more cost-effective and
      environmental friendly analytical methods is a major incentive to improve these
      conventional procedures and has spurred research in this field during the last
      decades. This review provides an overview of the most relevant developments and
      successful approaches proposed in recent years concerning sample preparation. The
      current state-of-the-art is discussed on the basis of examples selected from
      representative application areas and involving conventional instrumental
      techniques for the final determination of the target compounds. Emphasis will be
      on those techniques and approaches that have already demonstrated their
      practicality by the analysis of real-life samples, and in particular on those
      dealing with the determination of minor organic components. The potential of the
      latest developments in this field for sample treatment simplification and
      complete hyphenation and integration of analytical process is discussed and the
      most pressing remaining limitations evaluated.

PMID- 22137131
TI  - What I've learned.

PMID- 22137132
TI  - Claude H. Organ Jr Memorial Lecture. The care of the patient: character, science,
      and service.
AB  - Surgery as a profession rests on an age-old foundation based on 3 fundamental
      pillars: the collective character of our surgeons, their commitment to a practice
      based on science, and their pledge of service to humanity. The past 2 centuries
      bear witness to the success of surgical science. Significant improvement in the
      remaining 2 pillars is less evident. Our profession would be transformed in a
      positive way if we strengthened our commitment to improving our character while
      consciously building the character of our young, if we made the scientific method
      a way of life, and if we truly dedicated ourselves to the service of others.

PMID- 22137130
TI  - CFTR mutation analysis and haplotype associations in CF patients.
AB  - Most newborn screening (NBS) laboratories use second-tier molecular tests for
      cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease
      Control and Prevention's NBS Quality Assurance Program offers proficiency testing
      (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation
      detection. Extensive molecular characterization on 76 CF patients, family members
      or screen positive newborns was performed for quality assurance. The coding,
      regulatory regions and portions of all introns were sequenced and large
      insertions/deletions were characterized as well as two intronic di-nucleotide
      microsatellites. For CF patient samples, at least two mutations were
      identified/verified and four specimens contained three likely CF-associated
      mutations. Thirty-four sequence variations in 152 chromosomes were identified,
      five of which were not previously reported. Twenty-seven of these variants were
      used to predict haplotypes from the major haplotype block defined by HapMap data
      that spans the promoter through intron 19. Chromosomes containing the F508del
      (p.Phe508del), G542X (p.Gly542X) and N1303K (p.Asn1303Lys) mutations shared a
      common haplotype subgroup, consistent with a common ancient European founder.
      Understanding the haplotype background of CF-associated mutations in the U.S.
      population provides a framework for future phenotype/genotype studies and will
      assist in determining a likely cis/trans phase of the mutations without need for
      parent studies.

PMID- 22137133
TI  - Edgar J. Poth Memorial Lecture. Innovation in surgery: from imagination to
      implementation.
AB  - Surgeons, perhaps more than any other specialists, recognize the concept of
      furthering the current state of the art by making conscious changes, whether by
      tweaking how a surgical procedure is done to push the envelope of minimally
      invasive techniques, finding novel means of advancing surgical education in the
      face of work-hour restrictions, or advancing quality initiatives in an era of
      health care reform. Indeed, innovation seems to be the imperative to moving the
      field forward, for surgeons recognize that without continual process improvement,
      we stagnate in the status quo. This article pays tribute to Dr Edgar J. Poth by
      describing innovation in surgery as an iterative cycle beginning with an
      imaginative idea that is subjected to a series of "plan, do, check, act" quality
      cycles and ultimately is implemented as a new initiative, only to yield further
      creative ideas for improvement.

PMID- 22137134
TI  - Prognostic implications of anatomic location of primary cutaneous melanoma of 1
      mm or thicker.
AB  - BACKGROUND: Breslow thickness, ulceration, and sentinel lymph node (SLN) status
      are well established as the most important prognostic factors for patients with
      cutaneous melanoma. Anatomic location of the primary tumor is generally
      considered to play a minor role in determining prognosis compared with these
      other factors. This analysis was performed to better define the influence of
      anatomic location of the primary melanoma on prognosis. METHODS: In this post hoc
      analysis of a prospective randomized trial that included patients ages 18 to 70
      years with melanomas 1 mm or greater in Breslow thickness, all patients underwent
      SLN biopsy and completion lymphadenectomy if tumor-positive SLN were found.
      Kaplan-Meier survival analysis and univariate and multivariate analyses were
      performed to evaluate factors predictive of disease-free survival (DFS), local
      and in-transit recurrence-free survival (LITRFS), and overall survival (OS).
      RESULTS: A total of 2,500 patients were included in this analysis with a median
      follow-up period of 68 months. Anatomic locations included head, neck, trunk,
      upper extremity, and lower extremity. Age, Breslow thickness, and percentage of
      patients with a positive SLN were significantly different by anatomic location on
      univariate analysis, as were positive SLN status, presence of regression, sex,
      and histologic subtype (P < .0001). On multivariate analysis, anatomic location
      was an independent predictor of SLN status (P < .0001), DFS (P = .045), LITRFS (P
      = .023), and OS (P < .0001). By Kaplan-Meier analysis, anatomic location was
      associated significantly with DFS, LITRFS, and OS. CONCLUSIONS: Anatomic location
      of the primary melanoma is an important independent predictor of SLN status and
      prognosis. Patients with primary melanomas of the head/neck and trunk have a
      worse prognosis than primary melanomas of other anatomic locations.

PMID- 22137135
TI  - Incidence of blunt cerebrovascular injury in low-risk cervical spine fractures.
AB  - BACKGROUND: It has been suggested that specific cervical spine fractures (CSfx)
      (location at upper cervical spine [CS], subluxation, or involvement of the
      transverse foramen) are predictive of blunt cerebrovascular injury (BCVI). We
      sought to determine the incidence of BCVI with CSfx in the absence of high-risk
      injury patterns. METHODS: We performed a retrospective study in patients with
      CSfx who underwent evaluation for BCVI. The presence of recognized CS risk
      factors for BCVI and other risk factors (Glasgow coma score <= 8, skull-based
      fracture, complex facial fractures, soft-tissue neck injury) were reviewed.
      Patients were divided into 2 groups based on the presence/absence of risk
      factors. RESULTS: A total of 260 patients had CSfx. When screened for high-risk
      pattern of injury for BCVI, 168 patients were identified and 13 had a BCVI (8%).
      The remaining 92 patients had isolated low CSfx (C4-C7) without other risk
      factors for BCVI. In this group, 2 patients were diagnosed with BCVI (2%).
      Failure to screen all patients with CSfx would have missed 2 of 15 BCVIs (13%).
      CONCLUSIONS: We propose that all CS fracture patterns warrant screening for BCVI.

PMID- 22137136
TI  - Mopeds: the legal loophole for repeat driving while intoxicated offenders.
AB  - BACKGROUND: Mopeds have less stringent licensing laws than automobiles. Moped
      operators in motorized vehicle collisions (MVCs) exhibit significantly higher
      rates of driving while intoxicated (DWI) and higher blood alcohol levels than
      automobile or motorcycle operators. This study evaluates the public safety issue
      of DWI recidivism among moped operators. METHODS: Moped operators evaluated after
      MVCs were identified from 2007 to 2009. Demographics, hospital data, and
      Department of Motor Vehicles records were reviewed. RESULTS: Sixty-five moped
      operators were evaluated. Thirty-two (49%) had a positive blood alcohol level, 29
      (45%) had a previous DWI, and 21 (72%) of those were repeat offenders. Twenty
      five (38%) had a revoked license at the time of injury. Of these, 19 (76%)
      incurred multiple revocations. Twenty-two (34%) showed prior charges of driving
      with a revoked license (DWRL), with 15 (68%) incurring multiple DWRL charges.
      CONCLUSIONS: Moped operators are often intoxicated at the time of injury and
      represent a public safety hazard. The majority are recidivists with multiple
      alcohol-related traffic charges. Current laws allow repeat offenders the
      sustained opportunity to operate motorized vehicles. Re-evaluation of current
      moped laws is needed to keep habitual offenders off the road.

PMID- 22137137
TI  - Implementation of an acute care surgery service at an academic trauma center.
AB  - BACKGROUND: The establishment of acute care surgery is rapidly becoming a
      solution to meet emergency surgical needs. Challenges include competition for
      emergency surgery opportunities and the ability to economically sustain a
      practice. METHODS: Clinical activity was measured by reviewing the institutional
      and practice plan databases. Work relative value units and practice plan
      collection rates defined clinical activity and revenue. RESULTS: Operative
      procedures and intensive care unit activity accounted for 52% and 36% of
      activity, respectively. Although procedures on the digestive tract accounted for
      half of the operative activity, significant activity was observed in nearly all
      other systems. Overall clinical productivity remained constant but did
      demonstrate a 25% increase in operative work relative value units. Current
      billing activity supports 4.0 clinical full-time equivalents, but estimated
      collections would cover <73% of physician direct costs. CONCLUSIONS: The authors
      describe the implementation of an acute care surgery service that combines
      trauma, emergency general surgery, and surgical critical care in an established
      academic surgery department. Developing a sustainable economic model must include
      income sources other than patient service revenue.

PMID- 22137138
TI  - Esophageal salvage with removable covered self-expanding metal stents in the
      setting of intrathoracic esophageal leakage.
AB  - BACKGROUND: Intrathoracic contamination from esophageal perforation, staple line
      dehiscence, or trauma can be a preterminal event. In our institution, covered
      self-expanding metal stents have been used aggressively in the management of
      esophageal leak, but their use remains controversial. The primary objective of
      this study was to evaluate the efficacy of esophageal salvage using stents to
      assist in the management of intrathoracic esophageal leakage. METHODS: Over 38
      months, 63 patients with esophageal or gastric leaks were evaluated for stenting
      as primary treatment and identified using a prospective database. RESULTS: Fifty
      six patients were managed with endoscopic stenting as primary therapy and 30 of
      those patients required a thoracic intervention after stenting. Seven of these
      patients required esophageal diversion after stent failure. Thirty-day mortality
      was 10% in the patients with intrathoracic contamination. CONCLUSIONS: We suggest
      that the use of covered self-expanding metal stents in patients with
      intrathoracic leak after esophageal perforation is safe and offers esophageal
      salvage in 77% regardless of time of presentation.

PMID- 22137139
TI  - Nonsurgical management of blunt splenic injury: is it cost effective?
AB  - BACKGROUND: This study analyzed outcomes and cost of splenic embolization
      compared with surgery for the management of blunt splenic injury. METHODS: We
      performed a retrospective chart review of all patients admitted with isolated,
      blunt splenic injury. An intent-to-treat analysis was initially conducted.
      Outcomes and cost/charges were compared in patients treated with embolization and
      surgical treatment. RESULTS: Of 236 patients admitted with isolated, blunt
      splenic injury, 190 patients were ultimately managed by observation, 31 by
      splenic embolization, and 15 by surgical management. Comparing outcomes and cost
      data for splenic embolization versus surgical management, there was no
      significant difference in intensive care unit use, hospital stay, complications,
      or re-admission. Surgical management patients required more blood transfusions
      and incurred higher procedure charges. Conversely, splenic embolization patients
      underwent more radiologic evaluations and charges. Total procedure-related
      charges were higher for surgical management when compared with splenic
      embolization ($28,709 vs $19,062; P = .016), but total hospital cost and total
      hospital charges were not significantly different. CONCLUSIONS: Nonsurgical
      treatment of blunt splenic injury is safe and cost effective. Angioembolization
      was statistically similar to surgical therapy regarding cost.

PMID- 22137140
TI  - Autotransfusion of hemothorax blood in trauma patients: is it the same as fresh
      whole blood?
AB  - BACKGROUND: Autotransfusable shed blood has been poorly characterized in trauma
      and may have similarities to whole blood with additional benefits. METHODS: This
      was a prospective descriptive study of adult patients from whom >=50 mL of blood
      was drained within the first 4 hours after chest tube placement. Pleural and
      venous blood samples were analyzed for coagulation, hematology, and electrolytes.
      RESULTS: Twenty-two subjects were enrolled in 9 months. The following measured
      coagulation factors of hemothorax were significantly depleted compared with
      venous blood: international normalized ratio (>9 in contrast to 1.1, P < .001),
      activated partial thromboplastin time (>180 in contrast to 28.5 seconds, P <
      .001), and fibrinogen (<50 in contrast to 288 mg/dL, P < .001). The mean
      hematocrit (26.4 in contrast to 33.9), (P = .003), hemoglobin (9.3 in contrast to
      11.8 g/dL, P = .004), and platelet count (53 in contrast to 174 K/MUL, P < .001)
      of hemothorax were significantly lower than venous blood. A hemothorax volume of
      726 mL was calculated to be equivalent to 1 U of red blood cells. CONCLUSIONS:
      Hemothorax blood contains significantly decreased coagulation factors and has
      lower hemoglobin when compared with venous blood.

PMID- 22137141
TI  - Gender influences outcomes in trauma patients with elevated systolic blood
      pressure.
AB  - BACKGROUND: This analysis explored the association between gender and systolic
      blood pressure (SBP) in trauma patients and then established how gender
      influenced outcomes in those with elevated SBP. METHODS: Demographics and
      outcomes were compared using the Los Angeles County Trauma System Database and
      multivariable modeling determined predictors for SBP, pneumonia, and mortality.
      RESULTS: Age and male sex were significant predictors for increased SBP, whereas
      the Injury Severity Score (ISS) >=16 was a significant predictor for decreased
      SBP. In both male and female TBI patients, SBP >=160 mmHg was associated with
      increased pneumonia (Adjusted odds ratio [AOR] = 1.74, P = .002 and AOR = 2.37, P
      = .046, respectively), whereas SBP >=160 mmHg was a predictor for mortality only
      among male TBI patients (AOR = 1.48, P = .03). In non-TBI patients, SBP >=160
      mmHg was not a predictor for pneumonia or mortality in either sex. CONCLUSIONS:
      In this retrospective review of trauma registry data, men presented with higher
      SBP. In patients with TBI, regardless of gender, increased SBP was associated
      with increased pneumonia, and in men with TBI increased SBP was associated with
      increased mortality. The cause and relevance of these epidemiological findings
      require further investigation.

PMID- 22137142
TI  - Robotic telepresence: a helpful adjunct that is viewed favorably by critically
      ill surgical patients.
AB  - BACKGROUND: The purpose of this study was to assess how surgical intensive care
      unit (SICU) patients and their families would perceive robotic telepresence. We
      hypothesized that they would view such technology positively. METHODS: This
      research was an Institutional Review Board-approved prospective observational
      study. Our robotic telepresence program augmented the SICU multidisciplinary team
      rounding process. We anonymously surveyed patients and their families on their
      perceptions. Those who interacted at least once with the robot served as our
      participant base. RESULTS: Twenty-four patients and 26 family members completed
      the survey. Ninety-two percent of respondents were comfortable with the robot,
      and 84% believed communication was "easy." Ninety percent did not perceive the
      robot as "annoying" and 92% did not believe that "the doctor cared less about
      them" because of the robot. Ninety-two percent of respondents supported the
      continued use of the robot. CONCLUSIONS: Robotic telepresence was viewed
      positively by patients and their families in the SICU. Furthermore, they believed
      the robot was beneficial to their care and indicated their support for its
      continued use.

PMID- 22137144
TI  - Carnosine inhibits KRAS-mediated HCT116 proliferation by affecting ATP and ROS
      production.
AB  - Carnosine is a natural dipeptide that has generated particular interest for its
      antioxidant, anti-aging and especially for its antiproliferative properties. In
      this study, we demonstrate that carnosine inhibits the proliferation of human
      HCT116 colon cancer cells. In this cell line, the activating KRAS mutation
      induces mitochondrial ROS, the signaling molecules for cell proliferation. We
      observed that 50-100 mM carnosine decreases ATP and ROS concentration and induces
      cell cycle arrest in G1 phase. In HCT116 cells these effects are related to
      decreased ERK1/2 phosphorylation and increased p21waf1 protein. Our findings
      support the concept that carnosine could inhibit HCT116 cell growth via its
      antioxidant activity and its ability to affect glycolysis.

PMID- 22137145
TI  - Morphofunctional aspects of dental implants.
AB  - Although oral implantology is among the most beneficial developments of modern
      dentistry, the widely spread opinion that the long-term outcome of implants is
      superior to that of natural teeth has been refuted. To evade uncritical
      extractions, the morphofunctional properties of natural teeth and implant
      supported restorations are compared from a proprioceptive and occlusal trauma
      perspective. The periodontal ligament of natural teeth provides the central nerve
      system with feedback for sensory perception and motor control. Conversely, the
      lack of such proprioception causes lower tactile sensitivity and less coordinated
      masticatory muscle activity in implant-borne restorations and makes them more
      prone to occlusal overload and possible subsequent failure. Moreover, occlusal
      anomalies may be conducive to parafunctional activity, craniomandibular disorder,
      tinnitus, and headache. Oral implantology, therefore, has to take appropriate
      account of occlusal conditions and the biomechanical and neuromuscular aspects of
      masticatory function.

PMID- 22137143
TI  - Some evolutionary perspectives on Alzheimer's disease pathogenesis and pathology.
AB  - There is increasing urgency to develop effective prevention and treatment for
      Alzheimer's disease (AD) as the aging population swells. Yet, our understanding
      remains limited for the elemental pathophysiological mechanisms of AD dementia
      that may be causal, compensatory, or epiphenomenal. To this end, we consider AD
      and why it exists from the perspectives of natural selection, adaptation, genetic
      drift, and other evolutionary forces. We discuss the connection between the
      apolipoprotein E (APOE) allele and AD, with special consideration to APOE E4 as
      the ancestral allele. The phylogeny of AD-like changes across species is also
      examined, and pathology and treatment implications of AD are discussed from the
      perspective of evolutionary medicine. In particular, amyloid-beta (Abeta)
      neuritic plaques and paired helical filament tau (PHFtau) neurofibrillary tangles
      have been traditionally viewed as injurious pathologies to be targeted, but may
      be preservative or restorative processes that mitigate harmful neurodegenerative
      processes or may be epiphenoma of the essential processes that cause
      neurodegeneration. Thus, we raise fundamental questions about current strategies
      for AD prevention and therapeutics.

PMID- 22137146
TI  - The validity and reliability of the Turkish version of the University of
      Washington Quality of Life Questionnaire for patients with head and neck cancer.
AB  - PURPOSE: The University of Washington Quality of Life Questionnaire (UW-QOL) is
      an English-language survey used to assess the quality of life of patients with
      head and neck cancer. The present study aimed to translate this widely used
      questionnaire into Turkish according to international guidelines and to
      statistically determine its validity and reliability by administering it to
      native Turkish-speaking patients. MATERIALS AND METHODS: This prospective study
      was performed at Hacettepe University, Faculty of Medicine, Turkey. The study
      included patients newly diagnosed as having head and neck cancer. Translation and
      cultural adaptation of the questionnaire were performed first. Then, the
      translated version was tested on a consecutive series of patients seen in the
      department of otorhinolaryngology head and neck surgery and the department of
      radiation oncology between September 2006 and February 2008. The patients were
      asked to complete 3 sets of questionnaires. The first set was completed 1 day
      before the beginning of treatment, the second 3 months after the completion of
      treatment, and the third 10 days after the second questionnaire was completed.
      The first and second sets included the European Organization for Research and
      Treatment of Cancer Quality of Life Core Questionnaire-Turkish version and UW-QOL
      Turkish version. The third set included the Turkish UW-QOL only. Performance
      status was assessed and rated by a physician using the Karnofsky and ZEW
      (Zubrod/The Eastern Cooperative Oncology Group (ECOG)/World Health Organization)
      performance scales, synchronous with the first and second sets of questionnaires.
      RESULTS: The original English version of UW-QOL was carefully translated into
      Turkish, and a final Turkish version of UW-QOL was developed in an iterative
      fashion. To determine its validity and reliability, 67 patients were included in
      the study. Internal consistency (Cronbach alpha = .757) was adequate, and test
      retest reliability (interclass correlation coefficient, 0.941) was excellent. The
      composite scores of the translated UW-QOL were compared statistically with the
      European Organization for Research and Treatment of Cancer Quality of Life Core
      Questionnaire scores, Karnofsky and ZEW performance scales, T stage of the
      disease, and UW-QOL global questions scores to support the scale's construct
      validity, and statistically significant associations were observed. CONCLUSIONS:
      The Turkish UW-QOL appears to be a valid and reliable tool for use with Turkish
      patients with head and neck cancer; it can also be used in clinical
      investigations and routine clinical practice in Turkey.

PMID- 22137147
TI  - Femoral bone strains during antegrade nailing: a comparison of two entry points
      with identical nails using finite element analysis.
AB  - BACKGROUND: Antegrade femoral nailing has become the standard treatment for
      diaphyseal femoral shaft fractures. Concerns linger that improper location of the
      nail entry point may lead to iatrogenic fracture and further complications. This
      study used finite element analysis to compare the strain magnitude and
      distribution resulting from each of two entry points in the proximal femur during
      antegrade nailing. METHODS: A finite element model was created from a CT scan of
      a 37 year old male femur and of a standard antegrade nail. Using implicit time
      stepping, the nail was inserted through piriformis and trochanteric entry points
      and strain was computed at 9 anatomic locations. FINDINGS: The strain levels were
      higher overall when inserting a nail through the trochanteric starting point. The
      highest strain occurred immediately medial and lateral to the trochanteric entry
      point. The posterior greater trochanter also showed very high strain levels
      during nail insertion. All strain values for nail insertion through the
      piriformis entry point were less than 2000 MUm/m. INTERPRETATION: The
      trochanteric entry will have a much greater potential of iatrogenic fracture of
      the proximal femur during insertion of a nail. Strains with this entry point
      exceed the yield level of bone and the repeated loading with the progression of
      the nail could cause fissures or fractures. Caution should be taken during
      insertion of an antegrade nail when utilizing a lateral trochanteric starting
      point secondary to an increased risk of trochanteric fracture and lateral cortex
      fracture.

PMID- 22137148
TI  - Trajectories of health-related quality of life differ by age among adults:
      results from an eight-year longitudinal study.
AB  - To date, only a few studies have assessed determinants of health trajectories
      using longitudinal health survey data. Multilevel models were used to estimate
      health-related quality of life trajectories and assess factors associated with
      variations among trajectories, controlling for mortality effects and cohort
      membership. Four biennial cycles (1996/97-2004/05) of the Canadian National
      Population Health Survey were used. Information for 13,665 respondents, including
      those who were subsequently institutionalized and/or died, was used. A typical
      life-course trajectory was concave with a slow decline until the age of 60,
      followed by a more rapid decline. Receiving social assistance, lower education
      and not being married had significant negative impacts on trajectories for young
      (age 18-39) and middle-aged (40-64). Chronic conditions and health behaviours
      such as smoking were important for seniors (65+). It is important to focus on the
      most relevant and important determinants of health in each phase of life.

PMID- 22137149
TI  - An evaluation of a national program to implement the Cornell Scale for Depression
      in Dementia into routine practice in aged care facilities.
AB  - BACKGROUND: Screening tools have been recommended for use in aged care to improve
      the detection and treatment of depression. This study aimed to evaluate the
      impact of a program for the routine implementation of the Cornell Scale for
      Depression in Dementia in Australian facilities, to determine whether use of the
      instrument by nurses led to further monitoring of depressive symptoms, medical
      referral, and changes in treatments prescribed for depression. METHODS: A file
      review was completed for 412 participants out of a total of 867 older people
      (47.5%) who resided in ten aged care facilities. The review examined Cornell
      Scale assessment data, medication charts, medical history, nursing progress
      notes, and resident care plans. Nursing staff who administered the Cornell Scale
      to each participant were also interviewed, and ten facility managers took part in
      an interview to determine barriers to the effective implementation of the
      instrument. RESULTS: The Cornell Scale had been administered to 46.8% of the
      sample in the previous 12 months, with 25% of these participants scoring 9-13 and
      27% scoring 14 and above. Less than one third of the residents with high scores
      were monitored by the staff following the assessment. Only 18% of residents with
      high scores were referred for further assessment of depression, while 10%
      received a treatment change. CONCLUSIONS: The absence of a protocol for
      responding to high Cornell Scale scores limited the potential of this program to
      result in widespread improved treatment of depressed older people. The use of the
      Cornell Scale by aged care nurses with limited training raised concern.

PMID- 22137150
TI  - [Virtual reality for clinical assessment of elderly people: early screening for
      dementia].
AB  - Today, there are 24.3 million people suffering from dementia worldwide, that is a
      new case every 7 seconds (Ferri et al., 2005) and more than 80 million cases
      expected in 2040. Aging-related morbidity is a real social problem making
      screening a major challenge. Currently, screening and diagnostic tools for
      dementia remain independent from each other, screening tools being non-specific
      and diagnostic tools non-naturalistic. With the technological possibilities
      offered by virtual reality, it is becoming easier to investigate cognition and
      behavior in elderly people. Virtual reality allows a better understanding and
      assessment, and perhaps could stimulate cognitive functioning of elderly people.
      Combining measurements of cognitive impairment and disability might help close
      the gap between structural and naturalistic validity.

PMID- 22137151
TI  - Diagnostic pitfalls at admission in patients with acute superior mesenteric
      artery occlusion.
AB  - BACKGROUND: Acute superior mesenteric artery (SMA) occlusion leads to acute
      intestinal ischemia and is associated with high mortality. Early diagnosis is
      often missed, and confounding factors leading to diagnostic delays need to be
      highlighted. OBJECTIVES: To identify potential diagnostic laboratory pitfalls at
      admission in patients with acute SMA occlusion. METHODS: Fifty-five patients with
      acute SMA occlusion were identified from the in-hospital register during a 4-year
      period, 2005-2009. RESULTS: The median age was 76 years; 78% were women. The
      occlusion was embolic in 53% and thrombotic in 47% of patients. At admission,
      troponin I was above the clinical decision level (> 0.06 MUg/L) for acute
      ischemic myocardial injury in 9/19 (47%) patients with embolic occlusion.
      Elevated pancreas amylase and normal plasma lactate were found in 12/45 and
      13/27, respectively. A troponin I (TnI) above the clinical decision level was
      associated with a high frequency of referrals from the general surgeon to a
      specialist in internal medicine (p = 0.011) or a cardiologist (p = 0.024). The
      diagnosis was established after computed tomography angiography in 98% of the
      patients. The overall in-hospital mortality rate was 33%. Attempting intestinal
      revascularization (n = 43; p < 0.001), with a 95% frequency rate of completion
      control of the vascular procedure, was associated with a higher survival rate,
      whereas referral to the cardiologist was associated with a higher mortality rate
      (p = 0.018). CONCLUSION: Elevated TnI was common in acute SMA occlusion, and
      referral to the cardiologist was found to be associated with adverse outcome.
      Elevated pancreas amylase and normal plasma lactate values are also potential
      pitfalls at admission in patients with acute SMA occlusion.

PMID- 22137152
TI  - Hypovolemia-induced Cardiac Tamponade in a Patient with Hypothyroidism.
AB  - BACKGROUND: Pericardial effusion occurs frequently in patients with
      hypothyroidism and is typically mild. Although extremely uncommon, massive
      pericardial effusion can compromise hemodynamics and cause cardiac tamponade.
      Reduced plasma volume has been reported to induce cardiac tamponade in massive
      pericardial effusion, but to our knowledge, hypovolemia-induced cardiac tamponade
      has not been reported in cases of hypothyroidism with pericardial effusion.
      OBJECTIVES: We describe a case of hypothyroidism with cardiac tamponade due to an
      uncommon cause that, to our knowledge, has never been reported. CASE REPORT: A 64
      year-old woman with untreated hypothyroidism presented with acute abdominal pain
      and watery diarrhea. The patient experienced shock and cardiac arrest during the
      examination. Massive pericardial effusion was detected and cardiac tamponade was
      diagnosed. We suspected that the pericardial effusion was pre-existing due to an
      11-year history of untreated hypothyroidism. On presentation, there was no
      hemodynamic compromise. Watery diarrhea persisted and intravenous fluid
      supplementation may have been inadequate. Hypovolemia developed and induced
      cardiac tamponade in the presence of the massive pericardial effusion. Successful
      resuscitation was achieved after cardiopulmonary resuscitation, aggressive
      intravenous fluid supplementation, and immediate pericardiocentesis. CONCLUSION:
      Pericardiocentesis is indicated for hypothyroid patients with cardiac tamponade.
      We recommend the use of small, multi-hole catheters and daily measurement of
      drainage fluid. If the pericardial effusion does not resolve, a pericardial
      window with chest tube drainage should be performed.

PMID- 22137153
TI  - A foreign body found incidentally in a pediatric patient who was unable to
      communicate.

PMID- 22137154
TI  - An unusual cause of dysphagia: pericardial effusion after implantable
      cardioverter-defibrillator placement.
AB  - BACKGROUND: Dysphagia is a known complication of pericardial effusions. Most
      cases of pericardial effusions are idiopathic, infectious, and neoplastic, but
      can also occur after cardiac procedures. OBJECTIVE: To report the case of a
      patient who developed dysphagia from a sub-acute pericardial effusion caused by
      the placement of an implantable cardioverter-defibrillator (ICD). CASE REPORT: A
      62-year-old woman presented to the Emergency Department (ED) with a 2-day history
      of dysphagia. Imaging revealed a large pericardial effusion compressing the
      esophagus from the mid-thoracic level to the gastroesophageal junction. Ten days
      prior, a dual-chamber ICD with small-diameter active fixation leads was placed in
      the patient. There had been no apparent complications from the procedure,
      however, over this 10-day period she developed a sub-acute pericardial effusion
      from an incidental perforation during ICD lead placement that led to the
      extrinsic compression of the esophagus and her presenting symptom of dysphagia.
      The patient underwent pericardiocentesis for the pericardial effusion and she was
      discharged in stable condition. CONCLUSION: This case report highlights the
      importance of recognizing a non-cardiac complaint such as dysphagia as the
      primary symptom of a critical cardiac condition. With an increase in cardiac
      procedures anticipated, clinicians should consider the possibility of a
      pericardial effusion as a cause of dysphagia, especially for those patients with
      recent cardiac procedures.

PMID- 22137155
TI  - Bringing genetics back to psychiatric endophenotypes.

PMID- 22137156
TI  - Depression and inflammation: an intricate relationship.

PMID- 22137157
TI  - Surveillance of elevated blood lead levels in children in Torreon, Coahuila,
      Mexico, 1998-2010.
AB  - INTRODUCTION: Because children exposed to lead have a very high health risk,
      surveillance and prevention programs are very important to avoid short- and long
      term health effects. OBJECTIVES: To describe the trend for the blood lead levels
      over a 12-year period in environmentally exposed children and to document the
      actions implemented to reduce the blood lead levels. MATERIALS AND METHODS: We
      performed a retrospective cohort study of children aged 0-15 years who were
      enrolled in the Coahuila Health Secretary's Childhood Blood Lead Level
      Surveillance program. This database includes children from the city of Torreon,
      Coahuila, Mexico, where the biggest smelter in Latin America is located. RESULTS:
      A total of 151,322 observations were analyzed in the study. The percentage of
      samples with elevated blood lead levels decreased from 84.9% to 10.4% during 1998
      2010, and the decrease was greater in girls than in boys. CONCLUSION: According
      to the results of our study, the majority of strategies and activities to
      decrease blood lead levels in an environmentally exposed population should be
      focused on children aged 0-5 years, on the home environment, on preventing
      fugitive emissions from smelters and other sources and on the proper disposal and
      confinement of industrial residues.

PMID- 22137158
TI  - Inter- and intra-subject variability of kinetics of airway exhalation and
      deposition of particulate matter in indoor polluted environments.
AB  - PM(2.5) generated by indoor combustion activities can contribute significantly to
      personal PM exposure. The aims of this study were: (1) to validate a device
      specifically designed to study the kinetics of particle exhalation and the
      percentage of airway particle deposition (%DEP) in polluted indoor environments
      (welding fumes, environmental tobacco smoke - ETS) and (2) to assess the intra-
      and inter-subject variability of the signal. The device was tested on 14 subjects
      exposed to welding fumes and 10 subjects exposed to environmental tobacco smoke
      (ETS), performing repeated measures at different environmental PM concentrations.
      The intra-subject variability of the signal for particles with diameter 0.3-1.0
      MUm showed a geometric mean of %CV always below 6%, despite the values of %DEP.
      In the welding fume study, the increase in airborne 0.5-1.0 MUm PM concentrations
      between the consulting room and production department was explainable in terms of
      increased density due to the metallic composition of particles. The %DEP of 0.3
      1.0 MUm ETS particles decreased with airborne PM concentration due to the
      technical limits of a laser particle counter and the perturbation induced by the
      physical characteristics of ETS PM. However, also at those extreme conditions,
      the signal remained repeatable and the individual susceptibility to PM remained
      substantially unaltered. In conclusion, the versatility and portability of our
      device, together with the repeatability of the signal, confirmed that the
      kinetics of exhaled particles and %DEP could be routinely measured in polluted
      environments and used to define individual susceptibility to airborne particles.

PMID- 22137159
TI  - [1.6% peppermint oil solution as intestinal spasmolytic in retrograde endoscopic
      cholangiopancreatography].
AB  - OBJECTIVES: Intestinal peristalsis can impede explorations and interventions
      using retrograde endoscopic cholangiopancreatography. Systemic spasmolytics are
      frequently employed to reduce this phenomenon, in spite of the adverse anti
      cholinergic effects they are associated with. We proposed a formula using 1.6%
      peppermint oil solution with local use in order to avoid these adverse side
      effects. METHOD: We formulated a preparation of 1.6% peppermint oil solution in
      accordance with the medical literature. The effectiveness of the formula was
      evaluated in a semi-qualitative manner according to the reduction in peristalsis.
      RESULTS: We tested two different emulgents, and polysorbate provided the best
      results. The pilot study carried out with 8 patients demonstrated its
      effectiveness and safety in reducing intestinal peristalsis. CONCLUSIONS: 1.6%
      peppermint oil solution constitutes an effective and safe alternative to the use
      of systemic spasmolytics. More studies are needed with a larger sample size in
      order to establish its usefulness in normal clinical practice.

PMID- 22137161
TI  - [Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH
      SEIMC, SEFH and SEMPSPH consensus document].
AB  - The antimicrobial agents are unique drugs for several reasons. First, their
      efficacy is higher than other drugs in terms of reduction of morbidity and
      mortality. Also, antibiotics are the only group of drugs associated with
      ecological effects, because their administration may contribute to the emergence
      and spread of microbial resistance. Finally, they are used by almost all medical
      specialties. Appropriate use of antimicrobials is very complex because of the
      important advances in the management of infectious diseases and the spread of
      antibiotic resistance. Thus, the implementation of programs for optimizing the
      use of antibiotics in hospitals (called PROA in this document) is necessary. This
      consensus document defines the objectives of the PROA (namely, to improve the
      clinical results of patients with infections, to minimise the adverse events
      associated to the use of antimicrobials including the emergence and spread of
      antibiotic resistance, and to ensure the use of the most cost-efficacious
      treatments), and provides recommendations for the implementation of these
      programs in Spanish hospitals. The key aspects of the recommendations are as
      follows. Multidisciplinary antibiotic teams should be formed, under the auspices
      of the Infection Committees. The PROA need to be considered as part of
      institutional programs and the strategic objectives of the hospital. The PROA
      should include specific objectives based on measurable indicators, and activities
      aimed at improving the use of antimicrobials, mainly through educational
      activities and interventions based more on training activities directed to
      prescribers than just on restrictive measures.

PMID- 22137162
TI  - Study of compliance with prescription information sheet of trastuzumab
      prescriptions in a tertiary level hospital.
AB  - INTRODUCTION: This study compares trastuzumab's actual conditions of use in
      clinical practice with those officially described on its summary of product
      characteristics. We also measure the cost associated with its use. METHODS:
      Observational study of the prescription/indication of trastuzumab in a tertiary
      hospital from January 2006 to 31 December 2007. We analysed whether trastuzumab
      use in clinical practice complied with its summary of product characteristics,
      concerning the following: HER2 over expression, indication (breast cancer),
      treatment plan, line of treatment, dosage, frequency and number of cycles. To
      measure cost, we calculated the total number of milligrams used and then
      multiplied it by the laboratory's sale price per milligram plus VAT. RESULTS: All
      patients (n=77) used trastuzumab for breast cancer. Sixty-two point two percent
      of patients presented with HER2+++ over expression. Twenty-nine treatment plans
      were used, that were not authorised on the summary of product characteristics.
      The total trastuzumab cost during the study period was ?1537 622.73. CONCLUSIONS:
      Although trastuzumab is always used for breast cancer, it is used in conditions
      other than those described on its summary of product characteristics, both for
      HER2 over expression and treatment plans.

PMID- 22137163
TI  - Characteristics and outcome of patients with ganglioneuroblastoma, nodular
      subtype: a report from the INRG project.
AB  - AIM: Describe characteristics and outcome of INRG patients with
      ganglioneuroblastoma, nodular subtype (GNBn). PATIENTS AND METHODS: Amongst 4071
      patients in the INRG database with known INPC histological category, 232 patients
      with GNBn were identified. Patients were categorised by clinical, pathological
      and genetic characteristic. For event-free survival (EFS) and overall survival
      (OS), Kaplan-Meier curves and lifetables were generated, and the outcome of
      subgroups was compared using log rank test. RESULTS: Patients with GNBn were
      older (83% >18 months), a higher proportion had unfavourable INPC pathology
      (83%), and rarely had MYCN gene amplified tumours (2%). Otherwise, the
      distribution of clinical and biological risk factors including stage, ferritin,
      initial treatment, grade of NB differentiation, MKI, 11q, 1p, and 17q were
      similar between patients with GNBn and the overall INRG cohort. EFS and OS were
      54%+/-5% and 68%+/-5%, respectively. A cohort with superior outcome was
      identified: OS for GNBn patients younger than 18 months was 95%+/-5% (n=39) and
      for GNBn patients with stage 1, 2, 3, 4s was 95%+/-3% (n=125). Conversely, a poor
      outcome sub-group could also be identified: OS for stage 4 was 35%+/-7% (n=107).
      CONCLUSIONS: Patients with GNBn tumours are rare and have a very heterogeneous
      outcome. Except for LDH and MKI, the factors prognostic in the overall NB cohort
      are also prognostic in patients with GNBn. Similar to the overall NB cohort,
      patients with GNBn older than 18 months of age, with stage 4 disease represent a
      high-risk sub-group and should be considered for aggressive treatment upfront.

PMID- 22137164
TI  - Human equilibrative nucleoside transporter 1 (hENT1) expression is a potential
      predictive tool for response to gemcitabine in patients with advanced
      cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinoma (CC) is a rare cancer of the liver. Surgery offers
      the only chance for cure. When surgery is unfeasible, chemotherapy is the
      backbone of treatment. The combined administration of cisplatin and gemcitabine
      is considered standard of care. Human equilibrative nucleoside transporter 1
      (hENT1) is the major transporter responsible for gemcitabine uptake into cells.
      hENT1 expression is associated with an increased survival for patients receiving
      gemcitabine after pancreatic cancer surgery, suggesting that hENT1 is predictive
      of response to gemcitabine. AIM: To determine whether there is a correlation
      between the expression of hENT1 and disease outcome in CC. METHODS: A
      retrospective study on 43 patients treated at our centre with a locally advanced
      or metastatic CC, who received first line treatment with gemcitabine, was
      performed. RESULTS: For the whole population, median Progression Free Survival
      (PFS) and overall survival (OS) were 4.0 (95% Confidence Interval 2.7-5.3 months)
      and 10.0 months (95%CI 6.8-13.2 months), respectively. From the 26 samples
      available for hENT1 staining, 18 (69%) and 8 (31%) patients had high and low
      hENT1 immunostaining, respectively. The median PFS were 2.0 versus 6.0 months for
      low versus high staining respectively (p = 0.012). The median OS were 5.0 versus
      11.0 months for low versus high staining, respectively (p = 0.036). On
      multivariate analysis, hENT1 expression was the single independent predictive
      factor associated with prolonged PFS (HR 0.35, p = 0.023) and OS (HR 0.41, p =
      0.046). CONCLUSION: In this study we show the potential of hENT1 expression as a
      predictor of outcome in CC treated with gemcitabine. Larger studies are necessary
      to confirm these promising results.

PMID- 22137165
TI  - Magnetic assistance highly sensitive protein assay based on surface-enhanced
      resonance Raman scattering.
AB  - A simple and effective surface-enhanced Raman scattering (SERS)-based protocol
      for the detection of protein-small molecule interactions has been developed. We
      employed silver-coated magnetic particles (AgMNPs), which can provide high SERS
      activity as a protein carrier to capture a small molecule. Combining magnetic
      separation and the SERS method for protein detection, highly reproducible SERS
      spectra of a protein-small molecule complex can be obtained with high
      sensitivity. This time-saving method employs an external magnetic field to induce
      the AgMNPs to aggregate to increase the amount of atto610-biotin/avidin complex
      in a unit area with the SERS enhancement. Because of the contribution of the
      AgMNP aggregation to the SERS, this protocol has great potential for practical
      high-throughput detection of the protein-small molecule complex and the antigen
      antibody immunocomplex.

PMID- 22137166
TI  - Adsorption of Cu(II) from aqueous solution by anatase mesoporous TiO2 nanofibers
      prepared via electrospinning.
AB  - Anatase mesoporous titanium nanofibers (m-TiO(2) NFs) have been synthesized from
      calcination of the as-spun TiO(2)/polyvinyl pyrrolidone (PVP)/pluronic123 (P123)
      composite nanofibers at 450  degrees C in air for 3h. The structures and the
      physicochemical properties of m-TiO(2) NFs are characterized by scanning electron
      microscopy, X-ray diffraction, nitrogen adsorption-desorption isotherm analysis,
      and determination point of zero charge, respectively. An investigation of Cu(II)
      adsorption onto m-TiO(2) NFs has been studied in this research. The pH effect,
      adsorption kinetics, and adsorption isotherms are examined in batch experiments.
      Experimental data were analyzed using pseudo-first order and pseudo-second order
      kinetic models. It was found that adsorption kinetics were the best fitting by a
      pseudo-second order kinetic model. The optimum pH for Cu(II) adsorption was found
      to be 6.0. The equilibrium data were analyzed by the Langmuir, Freundlich,
      Temkin, and Dubinin-Radushkevich isotherm models, which revealed that the
      Freundlich isotherm is the best-fit isotherm for the adsorption of Cu(II).
      Compared to the TiO(2) NFs (regular anatase titanium nanofibers) in the same
      experimental conditions to elucidate the role of the mesoporous structure of m
      TiO(2) NFs, experimental results showed that the m-TiO(2) NFs had a better
      adsorption capacity for Cu(II) due to its higher surface area.

PMID- 22137167
TI  - Ratchet composite thin film for low-temperature self-propelled Leidenfrost
      droplet.
AB  - The droplet control, especially for the self-propelled Leidenfrost droplet, has
      attracted many researchers' attention in applied and fundamental fields. In this
      paper, the ratchet thin film was fabricated by magnetron sputtering and hybrid
      ion beams deposition. The micro- and nanoscale structure of the film was
      characterized by field emission scanning electron microscope. This study reports
      an interesting phenomenon that the self-propelled Leidenfrost water droplet was
      initiated at low temperature. The Leidenfrost point of droplets was controlled by
      the surface wettability and parameters of the asymmetric ratchet substrate. This
      novel self-propelled interfacial material and preparation technology can be
      expanded to the manufacture process and constructed a temperature-dependent
      tubule for microfluidic systems.

PMID- 22137168
TI  - Effective adsorption of sodium dodecylsulfate (SDS) by hydrocalumite (CaAl-LDH
      Cl) induced by self-dissolution and re-precipitation mechanism.
AB  - Hydrocalumite (CaAl-LDH-Cl) was synthesized through a rehydration method
      involving a freshly prepared tricalcium aluminate (C(3)A) with CaCl(2) solution.
      To understand the intercalation behavior of sodium dodecylsulfate (SDS) with CaAl
      LDH-Cl, X-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning
      electron microscopy (SEM), transmission electron microscope (TEM), X-ray
      photoelectron spectroscopy (XPS), inductively coupled plasma-atomic emission
      spectrometer (ICP), and elemental analysis have been undertaken. The sorption
      isotherms with SDS reveal that the maximum sorption amount of SDS by CaAl-LDH-Cl
      could reach 3.67 mmol g(-1). The results revealed that CaAl-LDH-Cl holds a self
      dissolution property, about 20-30% of which is dissolved. And the dissolved
      Ca(2+) and Al(3+) ions are combined with SDS to form CaAl-SDS or Ca-SDS
      precipitation. It has been highlighted that the composition of resulting products
      is strongly dependent upon the SDS concentration. With increasing SDS
      concentrations, the main resulting product changes from CaAl-SDS to Ca-SDS, and
      the value of interlayer spacing increased to 3.27 nm.

PMID- 22137169
TI  - Adsorption of modified dextrins on molybdenite: AFM imaging, contact angle, and
      flotation studies.
AB  - The adsorption of three dextrins (a regular wheat dextrin, Dextrin TY,
      carboxymethyl (CM) Dextrin, and hydroxypropyl (HP) Dextrin) on molybdenite has
      been investigated using adsorption isotherms, tapping mode atomic force
      microscopy (TMAFM), contact angle measurements, and dynamic bubble-surface
      collisions. In addition, the effect of the polymers on the flotation recovery of
      molybdenite has been determined. The isotherms revealed the importance of
      molecular weight in determining the adsorbed amounts of the polymers on
      molybdenite at plateau coverage. TMAFM revealed the morphology of the three
      polymers, which consisted of randomly dispersed domains with a higher area
      fraction of surface coverage for the substituted dextrins. The contact angle of
      polymer-treated molybdenite indicated that polymer layer coverage and hydration
      influenced the mineral surface hydrophobicity. Bubble-surface collisions
      indicated that the polymers affected thin film rupture and dewetting rate
      differently, correlating with differences in the adsorbed layer morphology.
      Direct correlations were found between the surface coverage of the adsorbed
      layers, their impact on thin film rupture time, and their impact on flotation
      recovery, highlighting the paramount role of the polymer morphology in the
      bubble/particle attachment process and subsequent flotation.

PMID- 22137170
TI  - Synthesis and characterization of TiO2@C core-shell nanowires and nanowalls via
      chemical vapor deposition for potential large-scale production.
AB  - TiO(2) nanowires and nanowalls core structures covered with carbon shell were
      selectively synthesized by a simple chemical vapor deposition (CVD) method using
      commercial titanium powder as the starting material. Morphology and structure of
      the products were characterized by scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM). The core shell structure is composed of
      single crystalline rutile titanium dioxide wrapped by amorphous carbon shell. By
      adjusting the growth temperature, morphology of the products can be controlled
      from one-dimensional nanowires to two-dimensional nanowalls. While TiO(2)@C
      nanowires were a preferred structure at higher temperature, TiO(2)@C nanowalls
      dominated the final product at lower temperature. A growth mechanism was proposed
      based on the initial growth state of these nanostructures, in which solid-state
      diffusion of the elements involved in the reaction was assumed to play an
      essential role. The obtained TiO(2)@C core shell structures may find potential
      applications in various nanoscale realms such as optoelectronic, electronic and
      electrochemical nanodevices and the simple synthesis procedure promises large
      scale production and commercialization of the titanium oxide@carbon
      nanostructures.

PMID- 22137171
TI  - Preparation of activated carbon derived from cotton linter fibers by fused NaOH
      activation and its application for oxytetracycline (OTC) adsorption.
AB  - The objective of this research is to produce high surface area-activated carbon
      derived from cotton linter fibers by fused NaOH activation and to examine the
      feasibility of removing oxytetracycline (OTC) from aqueous solution. The cotton
      linter fibers activated carbon (CLAC) was characterized by N(2)
      adsorption/desorption isotherms, Fourier transform infrared spectroscopy (FTIR),
      and scanning electron microscope (SEM). The results showed that CLAC had a
      predominantly microporous structure with a large surface area of 2143 m(2)/g. The
      adsorption system followed pseudo-second-order kinetic model, and equilibrium was
      achieved within 24h. The equilibrium data were described well by Langmuir
      isotherm. Thermodynamic study showed that the adsorption was exothermic reaction
      at low concentration and became endothermic nature with the concentration
      increasing. Competitive adsorption took place in the weakly acidic to neutral
      conditions. Under the strong acidity or strong alkaline condition, the adsorption
      of the oxytetracycline was hindered by electrostatic repulsion. The adsorption
      mechanism depended on the pH of the solutions as well as the pK(a) of the
      oxytetracycline.

PMID- 22137172
TI  - Photo-responsive properties of poly(NIPAM-co-AAc) microgel particles with
      absorbed, hydrophobically modified organic salts.
AB  - The absorption of two hydrophobically modified organic salts (HMOSs), containing
      azobenzene units, into poly(N-isopropylacrylamide-co-acrylic acid) microgel
      particles has been studied at pH 8 and 20  degrees C. These dispersions were then
      irradiated with UV light (wavelength 365 nm) for 10 min to observe the effect on
      the microgel particle properties, such as the adsorbed amount of the HMOS, the
      particle size, and the electrophoretic mobility. We show that irradiation of
      these dispersions with UV light can lead to induced, partial desorption of the
      HMOS molecules, with concomitant changes in the size and electrophoretic mobility
      of the microgel particles. This is due to a conformational switch (trans-form to
      cis-form) in the HMOS molecules, which reduces the strength of the hydrophobic
      interaction between the HMOS molecules and the isopropyl moieties within the
      microgel network. Moreover, the original absorbed amounts, size, and
      electrophoretic mobility values can be largely restored after storage in the dark
      for extended periods.

PMID- 22137174
TI  - As(III) oxidation by MnO2 coated PEEK-WC nanostructured capsules.
AB  - PEEK-WC nanostructured capsules were prepared by the phase inversion technique
      and used as support for the coating of a manganese dioxide layer. The coating was
      done by a chemical treatment of the capsules followed by a thermal one. The
      presence of the MnO(2) layer was confirmed by scanning electron microscopy (SEM),
      back scattering electron (BSE), energy dispersive X-ray (EDX) and X-ray
      diffraction (XRD) analysis. The produced capsules were, then, tested for As(III)
      oxidation in batch. The experiments consisted in treating 165 ml of As(III)
      solution with 1g of coated capsules at fixed temperature (15 degrees C) and pH
      (5.7-5.8). In particular, the efficiency of the system was investigated for
      different As(III) concentrations (0.1, 0.3, 0.7 and 1 ppm). For feeds at lower
      As(III) content (0.1-0.3 ppm), tests lasted for 8h, while prolonged runs (up to
      48 h) were carried out on more concentrated solutions (0.7 and 1 ppm). The
      produced capsules were able to oxidize As(III) into As(V) leading to complete
      conversion after 3 and 4h for feed concentrations of 0.1 and 0.3 ppm,
      respectively.

PMID- 22137175
TI  - Removal of Pb(II) from water by natural zeolitic tuff: kinetics and
      thermodynamics.
AB  - The present study was aimed at examining the ability of a natural zeolitic
      volcanic tuff to remove Pb(II) ions from aqueous solutions under various
      conditions. The effects of various parameters such as optimum adsorbent mass,
      contact time, pH of the medium, Pb(II) concentration, and temperature were
      investigated. In addition, different adsorption isotherms were obtained using
      concentrations of Pb(II) ions ranging from 1mg/L to 200mg/L. The adsorption
      process follows second-order reaction kinetics and follows the Langmuir
      adsorption isotherm. The thermodynamic parameters are discussed in this article,
      including changes in Gibbs free energy, entropy, and enthalpy, for the adsorption
      of Pb(II) on tuff, and it is revealed that the adsorption process was spontaneous
      and exothermic under natural conditions. The maximum removal efficiency of 92%
      was obtained at a pH of 5 with a 25-min contact time for a 10 g/L solid-to-liquid
      ratio and an initial heavy metal concentration of 100mg/L.

PMID- 22137173
TI  - Biallelic mutations in PLA2G5, encoding group V phospholipase A2, cause benign
      fleck retina.
AB  - Flecked-retina syndromes, including fundus flavimaculatus, fundus albipunctatus,
      and benign fleck retina, comprise a group of disorders with widespread or limited
      distribution of yellow-white retinal lesions of various sizes and configurations.
      Three siblings who have benign fleck retina and were born to consanguineous
      parents are the basis of this report. A combination of homozygosity mapping and
      exome sequencing helped to identify a homozygous missense mutation, c.133G>T
      (p.Gly45Cys), in PLA2G5, a gene encoding a secreted phospholipase (group V
      phospholipase A(2)). A screen of a further four unrelated individuals with benign
      fleck retina detected biallelic variants in the same gene in three patients. In
      contrast, no loss of function or common (minor-allele frequency>0.05%)
      nonsynonymous PLA2G5 variants have been previously reported (EVS, dbSNP, 1000
      Genomes Project) or were detected in an internal database of 224 exomes (from
      subjects with adult onset neurodegenerative disease and without a diagnosis of
      ophthalmic disease). All seven affected individuals had fundoscopic features
      compatible with those previously described in benign fleck retina and no visual
      or electrophysiological deficits. No medical history of major illness was
      reported. Levels of low-density lipoprotein were mildly elevated in two patients.
      Optical coherence tomography and fundus autofluorescence findings suggest that
      group V phospholipase A(2) plays a role in the phagocytosis of photoreceptor
      outer-segment discs by the retinal pigment epithelium. Surprisingly,
      immunohistochemical staining of human retinal tissue revealed localization of the
      protein predominantly in the inner and outer plexiform layers.

PMID- 22137176
TI  - Synthesis of composite by application of mixed Fe, Mg (hydr)oxides coatings onto
      bentonite--a use for the removal of Pb(II) from water.
AB  - The procedure for obtaining a bentonite based composite involves the application
      of mixed Fe and Mg hydroxides coatings onto bentonite particles in aqueous
      suspension and subsequent thermal treatment of the solid phase at 498 K.
      Structural and textural modifications of montmorillonite which occurred during
      the synthesis of composite were confirmed by XRD technique and N(2) adsorption at
      77K. The composite structure was found to be less ordered, while its specific
      surface area was about two times higher than the specific surface area of the
      starting/native bentonite. The effectiveness of the composite in Pb(II) removal
      from aqueous solutions at different initial concentrations, pH and ionic
      strengths of the solutions was examined. The equilibrium adsorption data were
      analyzed using three widely applied isotherms: Langmuir, Freundlich and Dubinin
      Radushkevich. The composite effectively removes both ionic and colloidal forms of
      Pb(II) from water and the maximum adsorption capacity obtained from the Langmuir
      equation was 95.88 mg/g. The main mechanisms of Pb(II) removal at low pH values
      were ion-exchange and outer-sphere surface complexation.

PMID- 22137177
TI  - Enhanced degradation of phenanthrene and pyrene in freshwater sediments by
      combined employment of sediment microbial fuel cell and amorphous ferric
      hydroxide.
AB  - The degradation of phenanthrene and pyrene in freshwater sediment was
      investigated under three kinds of treatments (addition of amorphous ferric
      hydroxide to sediments, employment of sediment microbial fuel cell (SMFC), and
      the combination of ferric addition and SMFC employment). After 240 days of
      experiments, it was found that the combined treatment led to the highest removal
      efficiencies of phenanthrene (99.47 +/- 0.15%) and pyrene (94.79 +/- 0.63%),
      while the employment of SMFC could obtain higher removal efficiencies than
      Fe(III) addition. The combined approach improved potentials of phenanthrene and
      pyrene biodegradation in sediments under anaerobic pathways except methanogenic
      condition, and also stimulated humification of organic matters in sediments. At
      the end of experiments, ratios of humic acid to fulvic acid in sedimentary
      organic matters reached to 2.967 +/- 0.240 in the combined treatment, and were
      only around 1.404-1.506 in the other treatments. Thus, organic matters in
      sediments in the combined treatment could adsorb tightly residual PAHs with less
      bioavailability. Considering both enhanced biodegradation and final sequestration
      of PAHs in sediments, the combined application of Fe(III) addition and SMFC
      employment offered a new promising remediation technology for contaminated
      sediments.

PMID- 22137178
TI  - Real-time virtual sonography, a coordinated sonography and MRI system that uses
      magnetic navigation, improves the sonographic identification of enhancing lesions
      on breast MRI.
AB  - This study verified that recently developed real-time virtual sonography (RVS) to
      coordinate a sonography image and the magnetic resonance imaging (MRI)
      multiplanar reconstruction (MPR) with magnetic navigation was useful. The purpose
      of this study was to evaluate the accuracy of RVS to sonographically identify
      enhancing lesions by breast MRI. Between December 2008 and May 2009, RVS was
      performed in 51 consecutive patients with 63 enhancing lesions. MRI was performed
      with the patients in the supine position using a 1.5-T imager with a body surface
      coil to achieve the same position as with sonography. To assess the accuracy of
      the RVS, the following three issues were analyzed: (i) The sonographic detection
      rate of enhancing lesions, (ii) the comparison of the tumor size measured by
      sonography and the MRI-MPR and (iii) the positioning errors as the distance from
      the actual sonographic position to the expected MRI position in 3-D. Among the 63
      enhancing lesions, 42 (67%) lesions were identified by conventional B-mode,
      whereas the remaining 21 (33%) initial conventional B-mode occult lesions were
      identified by RVS alone. The sonographic size of the lesions detected by RVS
      alone was significantly smaller than that of lesions detected by conventional B
      mode (p < 0.001). The mean tumor size provided by RVS was 12.3 mm for real-time
      sonography and 14.1 mm for MRI-MPR (r = 0.848, p < 0.001). The mean positioning
      errors for the transverse and sagittal planes and the depth from the skin were
      7.7, 6.9 and 2.8 mm, respectively. The overall mean 3D positioning error was 12.0
      mm. Our results suggest that RVS has good targeting accuracy to directly compare
      a sonographic image with MRI results without operator dependence.

PMID- 22137179
TI  - Representativeness of nodal sampling with endobronchial ultrasonography in non
      small-cell lung cancer staging.
AB  - The objective of our study was to determine the procedure-related requirements of
      mediastinal node sampling with endobronchial ultrasonography with real-time
      transbronchial needle aspiration (EBUS-TBNA) that would provide negative
      predictive value (NPV) for the identification of stage III disease in non-small
      cell lung cancer (NSCLC) high enough to consider the technique equivalent to
      cervical mediastinoscopy. Representative EBUS-TBNA was defined as a sampling
      procedure obtaining satisfactory samples from normal nodes in regions 4R, 4L and
      7 or diagnosing malignancy in mediastinal nodes. NPV was estimated using the
      results of postsurgical staging in patients who underwent surgery as a reference.
      Two-hundred ninety-six patients staged with EBUS-TBNA were included.
      Representative samples from regions 4R, 4L and 7 showing nonmalignant cytology
      were obtained from 98 patients (33.1%) and EBUS-TBNA detected N2/N3 disease in
      150 (50.7%). Accordingly, an EBUS-TBNA procedure accomplishing the
      representativeness criteria required for sampling was attained in 248 of the
      participating patients (83.8%). The NPV of the procedure in this setting was
      93.6%, with false-negative results only found in 5 patients, four of them with
      nodal metastasis out of the reach of EBUS-TBNA (regions 5, 8 and 9). In
      conclusion, representative sampling of regions 4R, 4L and 7 is achieved in more
      than 80% of patients staged using EBUS-TBNA, and in the procedures that attain
      this requirement a NPV >90% for mediastinal malignancy is reached, a figure
      equivalent to cervical mediastinoscopy.

PMID- 22137180
TI  - The 'magic button question' for those with a mood disorder--would they wish to re
      live their condition?
AB  - BACKGROUND: To determine any positive aspects of living with a clinical mood
      disorder, and indirectly address the question--"If you could live your life
      again, would you press the 'magic button' to experience life without a mood
      disorder?" METHOD: Patients referred to a tertiary mood disorder facility were
      asked to complete a series of questionnaires pursuing detailed historical
      information about their mood disorder, including its 'best' and 'worst' aspects.
      RESULTS: Of the 884 patients surveyed, 335 (38%) returned data on their mood
      disorder's advantages and/or disadvantages. Of these, 62.2% of the bipolar and
      22.4% of the unipolar patients stated that having their condition had advantages,
      with the most commonly nominated consequences being increased empathy and self
      awareness, enhanced relationships, a heightened appreciation of life and
      increased creativity. LIMITATIONS: The qualitative design disallows any
      inferences as to the exact cause of benefits described in this study, so that we
      cannot conclude that the patients perceived these benefits as attributable to
      depression or bipolar disorder alone. CONCLUSIONS: While some respondents may
      well have focussed on transient benefits associated with bipolar 'highs',
      analyses indicated that a distinct sub-set of both unipolar and bipolar patients
      experienced some benefits, arguing for introducing the principles of positive
      psychology into management of wellbeing plans. In essence, while mood disorders
      are--by definition--disabling, they may also have enabling consequences.

PMID- 22137181
TI  - Frontal regional homogeneity increased and temporal regional homogeneity
      decreased after remission of first-episode drug-naive major depressive disorder
      with panic disorder patients under duloxetine therapy for 6 weeks.
AB  - OBJECTIVE: We designed this study to investigate the changes of regional
      homogeneity (ReHo) after a 6-week duloxetine therapy in first-episode drug-naive
      major depressive disorder with panic disorder (FEMDDPD) patients. METHOD: 3T
      magnetic resonance imaging (MRI) scanning and ReHo functional MRI analysis were
      performed on 15 patients (male: 5; female: 10; age: 35.87+/-9.59 years old) at
      baseline and remitted status (sixth week) compared with 15 healthy control
      subjects (male: 4; female: 11; age: 34.30+/-9.87 years old) which were scanned
      twice within 6 weeks. The ReHo was analyzed by the REST toolbox (resting-state
      functional MRI data analysis toolbox). The ReHos of different time-points were
      compared by using paired t test function of REST. RESULTS: ReHo increased in
      right superior frontal cortex, right medial frontal cortex and decreased in right
      superior temporal cortex (uncorrected p<0.00005, cluster threshold>20, surface
      connected theory) after remission of symptoms in these FEMDDPD patients within 6
      weeks (improvements of clinician rating and self rating scale scores; post-hoc
      corrected p<0.001). No significant changes of ReHo were observed in the controls
      within 6 weeks (uncorrected p<0.1, no cluster threshold setting, surface
      connected theory). The changes of ReHo value were mildly correlated with
      improvements of clinical rating scales with age, gender, depression and anxiety
      severity as covariates. CONCLUSION: Our study suggested that differential
      modulations inside the default mode network probably were associated with
      remission of FEMDDPD symptoms after duloxetine therapy.

PMID- 22137182
TI  - The 2011 meeting of the International Federation of Placenta Associations.

PMID- 22137183
TI  - Highlights in clinical autonomic neurosciences: device-based therapy for
      resistant hypertension.

PMID- 22137184
TI  - Posture and hand load alter muscular response to sudden elbow perturbations.
AB  - Joint stiffness and stability are reliant on coordinated muscle activity which
      may differ depending on initial posture and loading during sudden perturbations.
      This study investigated the effects of arm posture and hand load on muscle
      activity during perturbations of the arm. Fifteen male participants experienced
      perturbations to the wrist causing elbow extension using a combination of three
      body postures (standing, supine, sitting) and three hand load conditions (no,
      solid, and fluid loads), with known and unknown timing. Surface EMG was collected
      from eight muscles of the right upper extremity. The response to sudden loading
      was examined using muscle activities pre (baseline) and post (reflex)
      perturbation. During the baseline period, known perturbation timing resulted in
      greater muscular activity than for unknown timing, while the opposite was found
      for the reflex period. During the reflex period with fluid load, biceps brachii
      and brachioradialis demonstrated increased activity of 2.4% and 4.0% of maximum
      respectively, from supine to standing. During the reflex period, the fluid load
      resulted in forearm co-contraction 23% and 47% greater than the solid and no load
      conditions. Body orientation and hand loading influenced muscular response to
      elbow perturbations. Muscle co-contraction at the elbow during known timing
      suggests a contribution to elbow joint stability that may reduce injury risk
      caused by sudden elbow loading.

PMID- 22137185
TI  - A pragmatic randomized controlled trial of computerized CBT (SPARX) for symptoms
      of depression among adolescents excluded from mainstream education.
AB  - BACKGROUND: Adolescents excluded from mainstream education have high mental
      health needs. The use of computerized Cognitive Behavioural Therapy (cCBT) has
      not been investigated with this group. AIMS: To test the efficacy of the SPARX
      cCBT programme for symptoms of depression among adolescents in programmes for
      students excluded or alienated from mainstream education. METHOD: Adolescents
      (32; 34% Maori, 38% Pacific Island, 56% male) aged 13-16 with Child Depression
      Rating Scale Revised (CDRS-R) scores indicating possible through to almost
      certain depressive disorder were randomized to SPARX to be completed over the
      following 5 weeks (n = 20) or to waitlist control (n = 12). Assessments were at
      baseline, 5 weeks and 10 weeks. Those in the wait condition were invited to
      complete SPARX after the 5 week assessment. RESULTS: Most participants (n = 26,
      81%) completed at least 4 levels of SPARX and 22 (69%) completed all 7 levels.
      Among the 30 (94%) participants who began treatment as randomized and provided 5
      week data, significant differences were found between cCBT and wait groups on the
      CDRS-R (baseline to 5-week mean change -14.7 versus -1.1, p<.001), remission (78%
      vs. 36%, p = .047) and on the Reynolds Adolescent Depression Scale (-4.6 vs. +3.2
      p = .05) but not on other self-rating psychological functioning scales. In intent
      to-treat analyses CDRS-R changes and remission remained significant. Gains were
      maintained at 10-week follow-up. CONCLUSIONS: SPARX appears to be a promising
      treatment for students with symptoms of depression who are in alternative
      schooling programmes for those excluded from mainstream education.

PMID- 22137186
TI  - Composition of the sequence downstream of the dengue virus 5' cyclization
      sequence (dCS) affects viral RNA replication.
AB  - RNA replication of dengue virus (DENV) requires an RNA-RNA mediated
      circularization of the viral genome, which includes at least three sets of
      complementary RNA sequences on both ends of the genome. The 5' and the 3'
      untranslated regions form several additional RNA elements that are involved in
      regulation of translation and required for RNA replication. Communication between
      the genomic termini results in a structural reorganization of the RNA elements,
      forming a functional RNA panhandle structure. Here we report that the sequence
      composition downstream of the 5' CS element in the capsid gene, designated as
      downstream CS (dCS) sequence - but not the capsid protein - also influences the
      ability of the viral genome to circularize and hence replicate by modulating the
      topology of the 5' end. These results provide insights for the design of reporter
      sub-genomic and genomic mosquito-borne flavivirus constructs and contribute to
      the understanding of viral RNA replication.

PMID- 22137188
TI  - How the interplay between antigen presenting cells and microbiota tunes host
      immune responses in the gut.
AB  - Coordination of immune responses in the gut is a complex task. In order to fight
      pathogens and maintain a defined population of commensal microbes, the mucosal
      immune system has to coordinate information from the external (luminal) and
      internal (abluminal) environment and respond accordingly. Dendritic cells (DCs)
      are crucial cell types involved in this process as they integrate these signals
      and direct immunogenic or tolerogenic responses. Here, we review how various
      functions of DCs depend on microbial stimuli and how these stimuli influence the
      course of immune activation.

PMID- 22137189
TI  - The effect of using standardized patients or peer role play on ratings of
      undergraduate communication training: a randomized controlled trial.
AB  - OBJECTIVES: Considering the expense of standardized patients (SP) for training
      communication skills and the convenience of peer role playing (RP) there is a
      surprising lack of studies directly comparing the two methods. METHODS: Fifth
      year medical students (N=103) were assigned to three groups receiving a training
      in counseling parents of sick children with RP (N=34) or SP (N=35) or to a
      control group (CG, N=34). We assessed self-efficacy, as well as objective
      performance in parent-physician communication using questionnaires and the
      Calgary-Cambridge-Observation-Guide Checklist in a six-station OSCE,
      respectively. RESULTS: The training led to an increase in self-efficacy ratings
      and in the post-intervention OSCE score after RP (p<.021 and p<.001 respectively)
      and SP-training (p<.007 and p<.006 respectively) compared to controls.
      Surprisingly, this benefit was higher after RP than after SP-training (p<.021)
      due to significantly higher performance in the domain understanding of
      parents'perspective (p<.001). CONCLUSION: Both RP and SP are valuable tools for
      training specific communication skills. RP offer a methodological advantage in
      fostering empathy for patient perspectives. PRACTICE IMPLICATIONS: Both peer-role
      play and standardized patients hold specific benefits for communication training.
      Peer-role-play seems to foster a more empathic approach towards patients'
      concerns justifying its prominent role in medical curricula.

PMID- 22137190
TI  - The cost effectiveness of Nucleic Acid Amplification Techniques for the diagnosis
      of tuberculosis.
AB  - BACKGROUND: There is wide variation in the techniques deployed to diagnose
      tuberculosis in the UK, with little agreement on which tools or strategies are
      cost effective. This analysis therefore comprehensively evaluated the cost
      effectiveness of currently available diagnostic strategies for routine diagnosis
      of TB in the NHS. METHODS: The analysis compared strategies consisting of Nucleic
      Acid Amplification Techniques, culture and microscopy. A decision tree was used
      to estimate costs and Quality-Adjusted Life Years (QALYs) from a UK health
      service perspective. The sensitivity and specificity of each test determined the
      true and false positive and negative results in patients suspected of having
      active tuberculosis. These results led to either early, correct diagnosis or
      delayed diagnosis and the associated costs and QALYs. The presence of active
      tuberculosis combined with the side effects of treatment was associated with
      reduction in quality of life. Costs included were test costs, drug costs and the
      management of tuberculosis. Drug costs were based on generic UK list prices.
      Uncertainty in the model was explored through probabilistic and deterministic
      sensitivity analyses. RESULTS/CONCLUSIONS: The cost effective strategy at
      threshold of L20,000 per QALY was a strategy using only sputum microscopy and
      culture routinely, meaning Nucleic Acid Amplification Techniques are not cost
      effective at baseline. When the prevalence of tuberculosis was increased,
      however, nucleic acid amplification became cost effective at the same threshold.
      Aside from the prevalence, the results were shown to be robust. At low
      tuberculosis prevalence, Nucleic Acid Amplification Techniques may not be cost
      effective but their potential in higher prevalence situations is considerable.

PMID- 22137187
TI  - The role of B cells in solid organ transplantation.
AB  - The role of antibodies in chronic injury to organ transplants has been suggested
      for many years, but recently emphasized by new data. We have observed that when
      immunosuppressive potency decreases either by intentional weaning of maintenance
      agents or due to homeostatic repopulation after immune cell depletion, the
      threshold of B cell activation may be lowered. In human transplant recipients the
      result may be donor-specific antibody, C4d+ injury, and chronic rejection. This
      scenario has precise parallels in a rhesus monkey renal allograft model in which
      T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse
      model using alemtuzumab to deplete T cells. Such animal models may be useful for
      the testing of therapeutic strategies to prevent DSA. We agree with others who
      suggest that weaning of immunosuppression may place transplant recipients at risk
      of chronic antibody-mediated rejection, and that strategies to prevent this
      scenario are needed if we are to improve long-term graft and patient outcomes in
      transplantation. We believe that animal models will play a crucial role in
      defining the pathophysiology of antibody-mediated rejection and in developing
      effective therapies to prevent graft injury. Two such animal models are described
      herein.

PMID- 22137191
TI  - Residual activity and integrity of PermaNet(r) 2.0 after 24 months of household
      use in a community randomised trial of long lasting insecticidal nets against
      visceral leishmaniasis in India and Nepal.
AB  - The World Health Organization (WHO) recommends several brands of long lasting
      insecticidal net (LN) for protection against insect vectors but also advises
      national programmes to monitor and evaluate performance under local conditions to
      help them select the most suitable LN for their setting. During the course of a
      community randomised trial of LNs against visceral leishmaniasis in northern
      India and Nepal, opportunity arose to assess the efficacy of PermaNet 2.0
      (Vestergaard-Frandsen, Denmark) after two years of use against sandfly vectors.
      Between 63% (India) and 78% (Nepal) of LNs became holed over the course of two
      years, deltamethrin residues fell from 55 mg/m(2) to an average of 11.6 mg/m(2)
      (India) and 27.9 mg/m(2) (Nepal), but on the basis of bioassay criteria all LNs
      tested still met the WHO Pesticide Evaluation Scheme standard for LN
      effectiveness. Nets had on average only been washed 2.5 times (India) and 0.6
      times (Nepal) by householders over the course of two years. The loss of
      insecticide was attributed to factors which had little or nothing to do with
      washing, such as handling, friction and torsion during daily use. Under
      conditions pertaining in this region of south Asia, and for two years at least,
      this brand of net continues to meet the criteria established by WHO for LNs.

PMID- 22137192
TI  - Is leishmaniasis widespread in Spain? First data on canine leishmaniasis in the
      province of Lleida, Catalonia, northeast Spain.
AB  - Canine leishmaniasis (CanL) is a widespread disease present in 42 countries. It
      is considered of epidemiological importance because of its role as a reservoir of
      human leishmaniasis. Knowledge of the real distribution of CanL and its emergence
      and/or re-emergence is of great importance in order to determine the extension of
      the disease. This work reports the detection of CanL in a farm dog located in a
      Pyrenean area of northwest Catalonia (Spain) where the disease was previously
      unknown. Since the dog had never left the region and sandfly vectors, Phlebotomus
      ariasi and P. perniciosus, were present in the farm the case is considered as
      autochthonous and is the first to be published in this region of Spain.

PMID- 22137193
TI  - [Pathologie Biologie: an evolution].

PMID- 22137194
TI  - Over-the-counter delivery of antibiotics: are we sending the right message?

PMID- 22137195
TI  - Effect of lateral epicondylosis on grip force development.
AB  - STUDY DESIGN: Case-Control. INTRODUCTION: Although it is well known that grip
      strength is adversely affected by lateral epicondylosis (LE), the effect of LE on
      rapid grip force generation is unclear. PURPOSE OF THE STUDY: To evaluate the
      effect of LE on the ability to rapidly generate grip force. METHODS: Twenty-eight
      participants with LE (13 unilateral and 15 bilateral LE) and 13 healthy controls
      participated in this study. A multiaxis profile dynamometer was used to evaluate
      grip strength and rapid grip force generation. The ability to rapidly produce
      force is composed of the electromechanical delay and rate of force development.
      Electromechanical delay is defined as the time between the onset of electrical
      activity and the onset of muscle force production. The Patient-rated Tennis Elbow
      Evaluation (PRTEE) questionnaire was used to assess pain and functional
      disability. Magnetic resonance imaging was used to evaluate tendon degeneration.
      RESULTS: LE-injured upper extremities had lower rate of force development (50
      lb/sec, confidence interval [CI]: 17, 84) and less grip strength (7.8 lb, CI:
      3.3, 12.4) than nonnjured extremities. Participants in the LE group had a longer
      electromechanical delay (- 59% , CI: 29, 97) than controls. Peak rate of force
      development had a higher correlation (r = 0.56; p<0.05) with PRTEE function than
      grip strength (r = 0.47; p<0.05) and electromechanical delay (r = 0.30; p>0.05)
      for participants with LE. In addition to a reduction in grip strength, those with
      LE had a reduction in rate of force development and an increase in
      electromechanical delay. CONCLUSIONS: Collectively, these changes may contribute
      to an increase in reaction time, which may affect risk for recurrent symptoms.
      These findings suggest that therapists may need to address both strength and
      rapid force development deficits in patients with LE. LEVEL OF EVIDENCE: 3B.

PMID- 22137196
TI  - Post-match changes in neuromuscular function and the relationship to match
      demands in amateur rugby league matches.
AB  - OBJECTIVES: The current study investigated the change in neuromuscular
      contractile properties following competitive rugby league matches and the
      relationship with physical match demands. DESIGN: Eleven trained, male rugby
      league players participated in 2-3 amateur, competitive matches (n = 30).
      METHODS: Prior to, immediately (within 15-min) and 2h post-match, players
      performed repeated counter-movement jumps (CMJ) followed by isometric tests on
      the right knee extensors for maximal voluntary contraction (MVC), voluntary
      activation (VA) and evoked twitch contractile properties of peak twitch force
      (Pt), rate of torque development (RTD), contraction duration (CD) and relaxation
      rate (RR). During each match, players wore 1 Hz Global Positioning Satellite
      devices to record distance and speeds of matches. Further, matches were filmed
      and underwent notational analysis for number of total body collisions. RESULTS:
      Total, high-intensity, very-high intensity distances covered and mean speed were
      5585 +/- 1078 m, 661 +/- 265, 216 +/- 121 m and 75 +/- 14 m min(-1),
      respectively. MVC was significantly reduced immediately and 2h post-match by 8 +/
      11 and 12 +/- 13% from pre-match (p<0.05). Moreover, twitch contractile
      properties indicated a suppression of Pt, RTD and RR immediately post-match
      (p<0.05). However, VA was not significantly altered from pre-match (90 +/- 9%),
      immediately-post (89 +/- 9%) or 2h post (89 +/- 8%), (p>0.05). Correlation
      analyses indicated that total playing time (r = -0.50) and mean speed (r = -0.40)
      were moderately associated to the change in post-match MVC, while mean speed (r =
      0.35) was moderately associated to VA. CONCLUSIONS: The present study highlights
      the physical demands of competitive amateur rugby league result in interruption
      of peripheral contractile function, and post-match voluntary torque suppression
      may be associated with match playing time and mean speeds.

PMID- 22137197
TI  - Weissella sp. outbreaks in commercial rainbow trout (Oncorhynchus mykiss) farms
      in Brazil.
AB  - The genus Weissella contains 14 bacterial species that usually occur in nutrient
      rich environments and in fermented foods and beverages. Outbreaks of hemorrhagic
      septicemia were reported in three commercial rainbow trout (Oncorhynchus mykiss)
      farms in Brazil in 2008 and 2009. Seventy-seven Gram-positive isolates were
      obtained from 41 diseased fish from these farms. The bacterial strains were
      identified as Weissella at the genus level using biochemical tests, Weissella
      genus-specific PCR, and 16S rRNA sequencing. To evaluate potential routes of
      infection, rainbow trout juveniles were experimentally infected with the
      pathogen. In addition, the resistance of the pathogen to five antibiotics was
      tested, and provisional epidemiological cut-off values were calculated using the
      normalized resistance interpretation (NRI). All isolates presented similar
      phenotypic profiles and positive reactions for Weissella genus-specific PCR. The
      16S rRNA sequences of the Brazilian strains showed 100% similarity with sequences
      of Chinese isolates that previously were identified as the first case of
      Weissella sp. infection in fish. The disease was successfully reproduced in the
      laboratory by intraperitoneal injection, immersion, and cohabitation between
      diseased and healthy fish. All isolates were resistant to sulfonamide, and based
      on NRI analysis, one, two, and three isolates were classified as non-wild-type
      (NWT) for erythromycin, oxytetracycline, and norfloxacin, respectively. This is
      the first description of multiple cases of Weissella sp. infection in rainbow
      trout farms outside of China, of infectious routes for the disease, and of
      provisional epidemiological cut-off values for resistance of these bacteria to
      four antibiotics.

PMID- 22137198
TI  - [Monitoring of quality indicators of prescriptions after acute myocardial
      infarction].
AB  - OBJECTIVES: Cardiovascular disease is the primary cause of death in the world.
      Various drugs have shown their efficiency in the management of patients with
      acute coronary syndrome, along with the recommendations established by different
      Scientific Societies. The objective of this survey is to assess the monitoring of
      the quality standards established in Andalusia for the management of patients
      with myocardial infarction with evaluation of the ST segment and to analyse the
      source of variability of the prescription provided by the physician. METHOD: An
      observational descriptive survey, of indication-prescription, which analysed all
      the prescriptions included in the hospital discharge reports in patients treated
      in a tertiary hospital after having suffered acute myocardial infarction with ST
      segment elevation, between August 2005 and July 2007. RESULTS: A total of 287
      patients were included. Antiplatelets were prescribed in 99.3% of the patients,
      and acetylsalicylic acid in 95.8%. The percentage of beta-blockers received was
      89.5%, angiotensin converting enzyme inhibitors (ACEI) in 74.2%, with ARA-II
      indicated in 2.85%. The use of statins was 84.6%. The indication of conditional
      sublingual nitroglycerin was 60.3%. The use of ACEI and sublingual nitroglycerin
      showed statistically significant differences according to the prescribing
      physician. CONCLUSIONS: The fitness of the prescriptions to the recommendations
      established in Andalusia is high. The prescription of conditional sublingual
      nitroglycerin is the indicator which varies most in the quality standards
      established. Its use in conjunction with the indication of ACEI, are the
      recommendations which show a higher deviation depending on the prescribing
      physician.

PMID- 22137199
TI  - [Panem et circenses or how football shows the use of emergency rooms at
      convenient times].

PMID- 22137200
TI  - [Morbidity and costs in complete thyroidectomies. Improvement in Value of the
      Process by a change in the management].
AB  - OBJECTIVES: 1) To present the postoperative morbidity of complete thyroidectomies
      and the results of their clinical management and costs obtained after surgery. 2)
      To compare the results obtained for the morbidity and costs in the complete
      thyroidectomy Process, after the management changes introduced by the Endocrine
      Surgical Unit (ESU). 3) To define whether these changes improve the Value
      (benefit/cost ratio) of the Process. MATERIAL AND METHODS: Prospective study of
      cohorts conducted on 529 complete thyroidectomies performed between 1998 and
      2011. We present their clinical-pathological characteristics and we compare the
      clinical and management results obtained after surgery in 2 time periods: 1998
      2006 without ESU (group 1, 205 patients) and 2007-2011 with ESU (group 2, 324
      patients). The clinical results and the possible benefits are assessed by
      studying the morbimortality (recurrent lesions, hypocalcaemia [<8 mg/dl],
      suffocative haematomas and bleeding), and those of management, for the evaluation
      of the use of operating room time, the average stay and the total cost of the
      Process. The statistical comparison study was made using Student t test, for the
      comparison of means and the Chi(2) to compare percentages, accepting P<.05 as
      significant. RESULTS: The global percentage of transient recurrent dysfunctions
      (TRD) was 6%, and for definitive recurrent paralysis (DRP) it was 1.5%.
      Hypocalcaemia, at 24 hours was 54.6%, at one month 7%, at six months 6.2% and
      that of definitive hypoparathyroidism 1.3%. There were 2.8% of suffocative
      haematomas and 2% adverse effects. The mean surgical time was 98 minutes, and the
      average stay was 3.66 days. In the comparison of results of the groups, the ESU
      improved the TRD index by nearly 7 points (10.2 vs. 3.4%, P=.002), that of DRP by
      1.5 (2.4 vs. 0.4%; P=.3) until reaching under 1%. The figures on bleeding at 24
      hours (53 vs. 44 cc; P=.002) and 48 hours (23 to 17 cc; P<.001), the rate of
      haematomas by another 6 points (6.3 vs. 0.6%; P<.001), and that of hypocalcaemia
      at 24 hours (P=.01). The average stay also improved (4.79 vs. 2.94 days; P<.001),
      the use of operating room time (reduced by 20 minutes/operation; P<.001), the
      total cost of the Process, decreasing by more than ? 2,000/Process (P<.001), and
      produced a total savings for the hospital in the period of study of ? 665,820.
      CONCLUSIONS: 1) The global results (post-operative morbidity) of our total
      thyroidectomies are within the quality standards. 2) The surgical specialisation
      and the changes introduced by the ESU improved the clinical results (greater
      benefit) and those of management, cutting down the average stay and the operating
      room usage time and decreasing costs. 3) The change in management increased the
      Value of the Process.

PMID- 22137201
TI  - [Patients' perspective and economic variables as objectives in clinical trials:
      added value to clinical parameters].
AB  - OBJECTIVE: Patient-reported outcome (PRO) measures complement traditional
      biomedical outcome measures. The purpose of this study was to evaluate the use of
      PRO measures including health-related quality of life (HRQoL) questionnaires as a
      measurement of efficacy and the frequency of inclusion of economic variables
      related to direct and indirect costs in the design of clinical trials and phase
      IV observational studies. Moreover, for the trials quality score were measured,
      and if there were any relationship between the quality study design score and the
      PRO inclusion. MATERIAL AND METHODS: Retrospective observational study of the
      clinical trials and phase IV observational studies approved by a Clinical
      Research Ethics Committee (2008-2010). We gathered data concerning general
      aspects including medical specialty, pathology, methodological quality based on
      Jadad scale (0-5), inclusion of PRO and economic variables. For clinical trials
      including HRQoL measurements, we analysed the type of questionnaire in use. Where
      there were no HRQoL measurements, we analysed if their inclusion would have been
      proper or not. RESULTS: A total of 70 protocols (59 CTs and 11 phase IV
      observational studies) were analysed; 37 (52.8%) included PRO measures, and 3
      protocols (4.3%) used them as a primary endpoint. Data analysis by therapeutic
      area showed that PRO measures were most commonly studied in the fields of
      endocrinology, neurology, digestive diseases, and cardiology. The average quality
      score for the trials was 2.8. The trials with more PRO inclusion in their end
      points had a significantly higher quality score. Only 13 (22%) clinical trials
      and 2 (18.2%) phase IV observational studies included economic variables.
      CONCLUSIONS: The emergence of economic variables in clinical trials and phase IV
      observational studies evaluated was low, however, more than half of the revised
      protocols have included PRO measures, reflecting the importance of these
      parameters in the assessment of the effectiveness of drug treatments, although
      its use is still not systematic.

PMID- 22137202
TI  - [Modification of specialised care prescriptions by Primary Healthcare
      physicians].
AB  - OBJECTIVE: To determine the percentage of new Specialist Healthcare prescriptions
      received and modified by Primary Healthcare physicians. DESIGN: Descriptive,
      cross-sectional and multi-centre study with the participation of Primary
      Healthcare physicians from one Madrid Health Area during 2 months. A method was
      established for registering the origin of the new prescriptions in the
      Computerised Medical Record System. In order to register new prescriptions
      without any change from Specialist Healthcare, the "second level" option was
      marked when the prescription was issued. A protocol was prepared and was
      available on the Computerized Medical Record System, so for those cases where
      there was a new Specialist Healthcare prescription, the Primary Healthcare
      physician would not issue any prescription or issue a prescription with changes
      as regards the original one. RESULTS: A total of 69 Primary Healthcare physicians
      from 15 Primary Healthcare centres registered 46,512 new prescriptions, 3,893
      (8.4%) from Specialist Healthcare. From this number, 3,544 prescriptions (91.0%
      95% CI: 90.1-91.9) were issued without changes, and 298 prescriptions were
      modified (7.7% 95% CI: 7.0-8.7). In 46 cases (1.2% 95% CI: 0.8-1.5) no
      prescription was issued. Some prescriptions were changed by 51% of Primary
      Healthcare physicians, and the median of prescriptions changed or not issued was
      3. The main reason for the modification was replacement with generics.
      CONCLUSIONS: A high percentage of new Specialist Healthcare prescriptions are
      issued without any changes being made by Primary Healthcare physicians.
      Modifications are concentrated in half of the participating physicians.
      Therefore, these data suggest that this practice is not generally adopted by the
      professionals.

PMID- 22137203
TI  - Highly sensitive voltammetric determination of lamotrigine at highly oriented
      pyrolytic graphite electrode.
AB  - The electrochemical behavior of lamotrigine (LMT) at the pyrolytic graphite
      electrode (PGE) is investigated in detail by the means of cyclic voltammetry.
      During the electrochemical reduction of LMT, an irreversible cathodic peak
      appeared. Cyclic voltammetric studies indicated that the reduction process has an
      irreversible and adsorption-like behavior. The observed reduction peak is
      attributed to a two-electron process referring to the reduction of azo group. The
      electrode showed an excellent electrochemical activity toward the electro
      reduction of LMT, leading to a significant improvement in sensitivity as compared
      to the glassy carbon electrode. The results of electrochemical impedance
      spectroscopy and cyclic voltammetry showed that edge-plane pyrolytic graphite
      electrode has excellent electrochemical response properties toward LMTs with
      respect to glassy carbon electrode modified with carbon nanotubes. High
      sensitivity, low detection limit and very good repeatability together with
      excellent recovery make the electrode as a powerful devise for accurate
      determination of LMT in pharmaceutical and biological samples.

PMID- 22137204
TI  - Direct electrochemistry of dopamine on gold-Agaricus bisporus laccase enzyme
      electrode: characterization and quantitative detection.
AB  - Direct electrochemistry of a new laccase enzyme immobilized on gold and its
      application as a biosensor for dopamine (DA) are investigated by voltammetry and
      electrochemical impedance spectroscopy. The sensor demonstrated a redox
      adsorption behavior with E(0') = + 180 mV vs. Ag/AgCl for immobilized Agaricus
      bisporus laccase (LacAB) enzyme. The MPA platform was assembled on Au with and
      without utilization of ultrasounds. Excellent results were obtained by using the
      enzyme electrode fabricated based on MPA assembled with sonication. The LacAB
      immobilized in this condition showed a large electrocatalytic activity for
      oxidation of DA. Accordingly, a third-generation (mediator free) biosensor was
      constructed for DA. The DA concentration could be measured in the linear range of
      0.5 to 13.0 and 47.0 to 430.0 MUmol L(-1) with correlation coefficients of 0.999
      and 0.989, respectively, and a detection limit of 29.0 nmol L(-1). The biosensor
      was successfully tested for determination of DA in human blood plasma and
      pharmaceutical samples.

PMID- 22137205
TI  - Fathers show modifications of infant-directed action similar to that of mothers.
AB  - Mothers' actions are more enthusiastic, simple, and repetitive when demonstrating
      novel object properties to their infants than to adults, a behavioral
      modification called "infant-directed action" by Brand and colleagues (2002). The
      current study tested whether fathers also tailor their behavior when interacting
      with infants and whether this modification differs from the infant-directed
      action that mothers show. A sample of 42 parents (21 mothers and 21 fathers)
      demonstrated the properties of two novel toys to their infants (12-month-olds)
      and to other adults. Fathers and mothers modified their actions with respect to
      repetitiveness, rate, range of motion, proximity, interactiveness, and enthusiasm
      compared with interactions with other adults. Fathers differed from mothers with
      respect to proximity, carrying out actions closer to their infants than mothers
      did. These results provide evidence that fathers show modifications in their
      infant-directed action that is similar to that of mothers.

PMID- 22137206
TI  - Retinal adherence and fibrillary surface changes correlate with surgical
      difficulty of epiretinal membrane removal.
AB  - PURPOSE: To correlate surgical difficulty of epiretinal membrane (ERM) removal
      with characteristics of ERM adherence seen by spectral-domain optical coherence
      tomography (SD-OCT). DESIGN: Prospective observational case series. METHODS:
      Surgical difficulty was correlated with extent of ERM adherence by SD-OCT using
      masked observers in consecutive eyes undergoing ERM removal (N=31). Surgical
      videos were analyzed and difficulty of ERM removal (grade 1-3) was determined in
      4 quadrants as well as the fovea by consensus of observers masked to SD-OCT
      findings. Extent of ERM adhesion was categorized (focal, broad, or complete) by
      masked observers using SD-OCT. The presence of fibrillary changes between the ERM
      and retinal nerve fiber layer (RNFL) was also evaluated. Surgical difficulty of
      ERM removal for each quadrant and fovea was compared to extent of ERM adherence
      and presence of fibrillary changes. RESULTS: Assessment of ERM adherence using SD
      OCT between masked observers was highly concordant (kappa=0.9178). Surgical
      difficulty of ERM removal was strongly associated with more extensive ERM
      adherence to the retina observed by SD-OCT. Complete ERM adherence correlated
      with an 8.6-fold increased surgical difficulty of ERM removal compared to focal
      adherence (P<.0001). The presence of fibrillary changes between the ERM and RNFL
      also correlated with a 25.5-fold increased difficulty of surgical removal
      compared to the absence of fibrillary changes (P<.0001). CONCLUSION: Extent of
      ERM-retinal adhesion and presence of fibrillary changes determined by SD-OCT
      provide reliable preoperative assessment of surgical difficulty. Furthermore, SD
      OCT analysis may help localize surgically advantageous coordinates to initiate
      ERM removal.

PMID- 22137207
TI  - Association between hyperreflective foci in the outer retina, status of
      photoreceptor layer, and visual acuity in diabetic macular edema.
AB  - PURPOSE: To determine if hyperreflective foci in the outer retina are associated
      with photoreceptor integrity and the logarithm of minimal angle of resolution
      (logMAR) visual acuity (VA) in patients with diabetic macular edema (DME).
      DESIGN: Retrospective, observational, cross-sectional study. METHODS: Patients
      (n=76; 108 eyes) with clinically relevant macular edema and no serous retinal
      detachment were analyzed retrospectively. Spectral-domain optical coherence
      tomography (SD-OCT) images were obtained for all patients. We investigated the
      relationship between the hyperreflective foci in the outer retinal layers of the
      external limiting membrane (ELM) at the fovea and the photoreceptor integrity and
      VA. RESULTS: SD-OCT showed that 58 eyes (53.7%) had hyperreflective foci in the
      outer retinal layers, and 107 eyes (99.1%) had hyperreflective foci in the inner
      retinal layers. The logMAR VA was significantly (P<.0001) worse in eyes with
      hyperreflective foci in the outer retinal layers than in eyes without them
      (0.463+/-0.382 vs 0.127+/-0.206, respectively). Disruption of the ELM line on OCT
      was significantly (P<.0001, for both comparisons) associated with both
      hyperreflective foci in the outer retinal layers and poor logMAR VA. Disruption
      of the junction of the inner and outer segment line (IS/OS) also was related to
      hyperreflective foci in the outer retinal layers and poor logMAR VA (P<.0001 for
      both comparisons). CONCLUSIONS: The presence of hyperreflective foci in the outer
      retina is closely associated with a disrupted ELM and IS/OS line on SD-OCT images
      and decreased VA in DME.

PMID- 22137208
TI  - Progressive constriction of the hyperautofluorescent ring in retinitis
      pigmentosa.
AB  - PURPOSE: To evaluate the constriction of the hyperautofluorescent ring over time
      in patients with retinitis pigmentosa (RP). DESIGN: Prospective study. METHODS:
      Fourteen eyes of 14 RP patients with a hyperautofluorescent ring were studied.
      Ring constriction was evaluated by measurements of its external and internal
      boundaries along the vertical and horizontal axes at baseline and at 12-, 24-, 36
      , and 48-month follow-ups. Repeat fundus autofluorescence was obtained at 12, 24,
      36, and 48 months in 13, 7, 5, and 1 eyes respectively. Spectral-domain optical
      coherence tomography (SD-OCT) images were obtained on 8 eyes and the horizontal
      extent of the inner segment/outer segment (IS/OS) junction was measured. SD-OCT
      was repeated at 12 and 24 months in 6 and 4 eyes respectively. RESULTS: The
      external boundaries of the ring were identified along the horizontal axis in 12
      eyes and along the vertical axis in 13. Internal boundaries were identified in 7
      eyes. Constriction was demonstrated in all patients except 1 who demonstrated
      minimal expansion of the internal boundary along the horizontal axis. SD-OCT
      measurements showed a decrease in the IS/OS junction length. CONCLUSION:
      Progressive constriction of the hyperautofluorescent ring and a concordant
      decrease in IS/OS junction length were observed over time.

PMID- 22137209
TI  - Proteomic alteration of Marc-145 cells and PAMs after infection by porcine
      reproductive and respiratory syndrome virus.
AB  - Viral infections usually result in alterations in the host cell proteome, which
      determine the fate of infected cells and the progress of pathogenesis. To uncover
      cellular protein responses in porcine reproductive and respiratory syndrome virus
      (PRRSV), infected pulmonary alveolar macrophages (PAMs) and Marc-145 cells were
      subjected to proteomic analysis involving two-dimensional electrophoresis (2-DE)
      followed by MALDI-TOF-MS/MS identification. Altered expression of 44 protein
      spots in infected cells was identified in 2D gels, of which the 29 characterised
      by MALDI-TOF-MS/MS included 17 up-regulated and 12 down-regulated proteins. Some
      of these proteins were further confirmed at the mRNA level using real-time RT
      PCR. Moreover, Western blot analysis confirmed the up-regulation of HSP27,
      vimentin and the down-regulation of galectin-1. Our study is the first attempt to
      analyze the cellular protein profile of PRRSV-infected Marc-145 cells using
      proteomics to provide valuable information about the effects of PRRSV-induced
      alterations on Marc-145 cell function. Further study of the affected proteins may
      facilitate our understanding of the mechanisms of PRRSV infection and
      pathogenesis.

PMID- 22137210
TI  - [Law, practice: How to collect the reports of psychiatric disorders in electronic
      patient's records?].

PMID- 22137211
TI  - [Abstinence from cocaine after long-term addiction].
AB  - BACKGROUND: Experimental data strongly suggest that in animal and probably in
      man, noradrenergic and serotoninergic become uncoupled during repeated
      consumption of drugs of abuse, strongly suggesting that different drugs share
      common mechanisms for drug-dependence. Using cocaine-dependence as model of
      strong addiction we speculate that careful analysis of psychic adjustments in
      patients who experience prolonged abstinence could be a useful tool for patient's
      care. AIM: The aim of this retrospective study was first to establish
      similarities in patients' histories concerning modes of entrance, circumstances
      favouring the stopping, and modality of withdrawal. Secondly, we analysed the
      different ways used by subjects to substitute their cocaine-dependence. PATIENTS
      AND METHODS: Cocaine-dependent subjects who had succeeded in supporting
      abstinence for at least 12 months without consumption were evaluated
      retrospectively by a face-to face interview. RESULTS: We obtained a list of
      circumstances associated with entries and exit from cocaine-dependence. Second,
      when seeking for similarities in addictive behaviour, before and after, between
      cocaine users, we proposed to classify patients according to the strength in
      their addictive dominant trait between strong, moderate, mild, or absence of
      addictive behaviour. For didactic aims, purposes are illustrated by clinical
      vignettes. CONCLUSIONS: This retrospective study allows us to clear arbitrarily
      four types of psychical modifications associated with prolonged abstinence in
      cocaine-dependent patients. Prospective clinical studies are clearly needed to
      standardize and to validate these clinical criteria.

PMID- 22137212
TI  - [To an integrative management of pathological gamblers].
AB  - INTRODUCTION: Recent researches on pathological gambling indicate that the
      various gambling activities are heterogeneous by nature. Indeed, some findings
      support the view that gambling cannot be seen as a homogeneous activity.
      Therefore, pathological gamblers do not represent a homogeneous population.
      However, treatment does not appear to take into account this heterogeneity and
      studies in the field have assessed the efficacy of the various types of
      treatment. Furthermore, recent empirical data emphasize the need for delineating
      distinct subtypes of pathological gambling presenting similar symptoms but which,
      at the same time, differ on certain variables. These subtypes will be essential
      in the management, treatment, and prognosis of pathological gambling. LITERATURE
      FINDINGS: Blaszczynski and Nower (2002) identified three subtypes of gamblers.
      The first subtype, referred to as the "emotionally vulnerable problem gamblers",
      includes gamblers who mainly gamble to escape painful emotional experiences. The
      second includes "antisocial impulsivist problem gamblers" who are mainly driven
      by impulsivity and sensation seeking. The last one, referred to as the
      "behaviourally conditioned problem gamblers", includes gamblers who gamble
      because of behavioural contingencies offered by the game, rather than
      psychological difficulties. Each group is characterized by specific psychological
      variables, and each may require a different treatment approach. Hence, these
      subgroups should be used and taken into account in the choice of the treatment.
      AIM OF THE PAPER: The purpose of this article is to provide an integrative model
      of treatment of this disorder based on the typology of pathological gamblers.
      Many studies have tried to understand this pathological behaviour by exploring
      motivational, psychological, biological and ecological correlates of gambling to
      explain the aetiology. An approach integrating various orientations, at the same
      time cognitive-behavioural, motivational, psychoanalytical and bodily-centred is
      the most relevant for this behavioural disorder. On the one hand, treatment
      should focus on the similarities displayed by the gambler. On the other hand,
      treatment should evaluate and focus on the specificities of each subtype of
      pathological gamblers. This last point refers to the question of the role played
      by the game for the gambler. All pathological gamblers present similar symptoms.
      Concerning those common points, professionals should evaluate and treat
      comorbidities, wrong perceptions/cognitions, motivation to change, gambling
      behaviour and social aspects of the gambling behaviour. Concerning the
      specificities, professionals should evaluate to which subtype or pathway the
      gambler corresponds, and then adapt the treatment. For example, for emotionally
      vulnerable problem gamblers gambling to escape painful emotional experiences and
      presenting alexithymia components, specific psychotherapeutic techniques
      improving affect identification and differentiation should be applied. Thus, add
      on individual psychoanalytical oriented sessions and relaxation sessions should
      be included in the treatment.

PMID- 22137213
TI  - [Description of medicosocial profiles of pharmacodependent subjects consulting
      addictology centres using a computerized database].
AB  - INTRODUCTION: Lots of similar vulnerabilities to substance use disorders are
      described in the literature: clinical, genetics, family, environment, etc.
      Although, when we follow up patients, we know perfectly well that there are also
      differences due to the substance mainly causing addiction. But we found very
      little research on the differences between various substance use disorders
      according to the substance mainly causing dependence. HYPOTHESIS: Our main
      hypothesis was that significant differences do not exist in medical and social
      data between patients with substance use disorders according to the substance
      mainly used. We expected to find significant differences between illegal
      substance use disorders (opiates, cocaine, cannabis) and legal substance use
      disorders (BZD, alcohol). OBJECTIVE: Our study aimed to identify differences
      between patients with substance related disorders in medical and social data
      according to the main addictive substance. MATERIAL AND METHOD: A specific
      software has been created by the CEIP and the Department of Addictology of Nantes
      University Hospital. Anonymous data were gathered and all patients gave their
      written consent. This database has been declared to CNIL (number 1350706). All
      data have been directly collected by the physician during medical consultation.
      The following data were recorded during the first medical examination: age, sex,
      illicit substance use, prior criminal record or psychiatric disorders, prior
      addictive behaviours among relatives and/or friends, family history (divorce,
      separation, abandonment). Other data were gathered prospectively:
      socioprofessional insertion, marital status, drug prescriptions (time and
      duration). RESULTS: We found significant differences in social (age, sex) and
      medical data (prior psychiatric disorders) between patients according to the
      substance causing dependence. We identified five profiles depending on the
      substance: cannabis, cocaine, heroin, alcohol and benzodiazepine. DISCUSSION: We
      clearly identified different types of patient's profiles according to substances
      mainly causing addiction. These differences can modify our strategies of
      prevention and treatment, so as to meet patients' needs better.

PMID- 22137214
TI  - [A preliminary validation of a new French instrument to assess quality of life
      for caregivers of patients suffering from schizophrenia].
AB  - INTRODUCTION: Since psychiatric institutions began discharging mentally ill
      patients into the community, family of patients suffering from schizophrenia are
      more and more involved in the therapeutic process. The adverse consequences of
      having a patient suffering from schizophrenia at home are called "burden of care"
      and have been studied by numerous authors. We were interested in the quality of
      life of caregivers and its evaluation. This concept represents a more complex,
      multidimensional approach in which many variables are taken into account. We
      propose the development of a French self-administered instrument of quality of
      life for caregivers of individuals with schizophrenia, the caregiver
      schizophrenia quality of life questionnaire (S-CGQoL). METHODS: Data were
      collected through the departments of six psychiatric hospitals in France (n=246).
      The item reduction and validation processes were based on both item response
      theory and classical test theory. The study of external validity used the generic
      Short Form 36 questionnaire. Scores of isolated dimensions were also confronted
      with caregivers' and patients' demographic data and with patients' clinical data.
      RESULTS: The S-CGQoL contains 25 items describing seven dimensions (psychological
      and physical well-being; burden and daily routine; relationships with spouse;
      relationships with psychiatric team; relationships with family; relationships
      with friends; and material burden). The seven-factor structure accounted for
      74.4% of the total variance. Internal consistency was satisfactory; Cronbach's
      alpha coefficients ranged from 0.79 to 0.92 in the whole sample. The scalability
      was satisfactory, with INFIT statistics within an acceptable range. In addition,
      the results confirmed the absence of DIF and supported the invariance of the item
      calibrations. Acceptability was good. The study of external validity found
      significant correlation between S-CGQoL index and all SF-36 dimension scores.
      Certain dimensions of the S-CGQoL are associated with caregivers' characteristics
      (age, sex, number of children, living situation, and employment status).
      Moreover, some domains of caregiver's quality of life are dependant on subtype of
      schizophrenia (paranoid) and symptomatology (positive factor and general
      psychopathology). We did not find any correlation with negative factor.
      DISCUSSION: The content of the S-CGQoL encompasses experiences of great
      importance to patients and is substantially different from other generic quality
      of life or burden instruments. In our questionnaire, the focus on the different
      aspect of the social life permits a precise analytical description of the social
      dimension that is not assessed as much in other questionnaires. LIMITATIONS: The
      psychometric properties need to be studied in a wider population. Some parameters
      of internal validity are missing, such as reproductibility (test-retest
      reliability) and sensibility to change. The external validity needs to study
      relationships between S-CGQoL and burden. CONCLUSION: The S-CGQoL is the first
      self-administered quality of life questionnaire for caregivers of patients
      suffering from schizophrenia. It presents satisfactory psychometric properties,
      which can be completed in five minutes and, therefore, fulfils the goal of
      brevity sought in research and clinical practice.

PMID- 22137215
TI  - [Psychosis and trauma. Theorical links between post-traumatic and psychotic
      symptoms].
AB  - INTRODUCTION: The co-occurrence between post-traumatic symptoms and psychotic
      symptoms is well described in the immediate suites of a trauma but can also be
      chronic. This symptomatic co-occurrence, rarely studied in the literature, is
      often approached under the sole angle of a primary post-traumatic stress disorder
      (PTSD) or of a primary psychosis, without federative will to unify the psychotic
      and post-traumatic symptoms within the same nosological framework. Individuals
      with schizophrenia or schizoaffective disorder report higher rates of trauma and
      assault than the general population. LITERATURE FINDINGS: High rates of PTSD have
      been noted in severe mental illness cohorts. Psychotic phenomena may be a
      relatively common manifestation in patients with chronic PTSD. AIM: The purpose
      of this paper is to expose the various theorical psychopathological aspects
      between the symptoms of psychosis and PTSD. In populations of veterans, positive
      and negative symptoms of psychosis in PTSD are described as delusional thoughts
      and hallucinations often combat-specific. CLINICAL FINDINGS: When a PTSD becomes
      established at a subject to the personality of neurotic structure, the intensity
      of the PTSD's symptoms lead to a psychotic expression which constitutes a factor
      of seriousness. Besides, PTSD often induces a risk of substance use disorder
      supplying psychotic symptoms. Cannabis increases the hallucinations, cocaine
      strengthens an underlying paranoid tone, and alcohol implies withdrawal
      hallucinosis. Moreover, such consumption could be a risk factor for the future
      development of chronic psychosis. From another point of view, by basing
      themselves on the plasma dopamine beta-hydroxylase activity, some authors made
      the analogy between psychotic major depression and PTSD with psychotic features
      (also characterized as a distinct psychotic subtype of PTSD). However, other
      studies found no correlation between PTSD with psychotic features and family
      predisposition for schizophrenia or schizoaffective disorder. DISCUSSION: The
      determination of the structure of personality seems fundamental in the
      understanding of the symptoms. A personality of psychotic structure increases the
      risk of traumatization and PTSD. At the same time, the fragility of this
      structure causes an increased sensitivity to the trauma, which takes on a
      particular echo. Moreover, a trauma can test a latent psychotic structure to
      reveal its existence. The experience of psychosis may be traumatic in itself for
      patients with, notably, seclusion and sedation during hospitalization. Lastly,
      the symptoms of this post-traumatic psychosis will be differentiated from
      neurological confusion caused by a traumatic brain injury. Clinicians often fail
      to screen routinely for trauma and PTSD symptoms in patients with severe mental
      illness because few systematic guidelines exist for the identification and
      treatment of this comorbidity. CONCLUSION: The links between psychotic and psycho
      traumatic symptoms are complex and multidirectional; this co-occurrence is a
      factor of seriousness. The clinician, while paying attention to these symptoms,
      has to distinguish the structure of the personality of the subject to articulate
      the psychotherapy and the pharmacological treatment. Further investigational
      studies may determine whether antipsychotics will enhance treatment response in
      PTSD patients with psychotic features.

PMID- 22137216
TI  - [The mental stress of the accompaniment in Alzheimer's disease].
AB  - INTRODUCTION: Alzheimer's disease affects patients in time and space and all
      dimensions of emotional, cognitive and social life. It is, in return, an
      unprecedented threat for the family, a disaster for each member of the family.
      Because of the love story, because of the suffering, the disease remains the
      relationship between patient and caregiver. We try to approach their suffering
      according to the carer's reports. Our research, conducted with support from
      France Alzheimer, aims to understand the nuances of the experience of becoming
      the accompanying person, drawing on some key moments of this accompaniment.
      METHODOLOGY: It is through an exploratory research that we met eight caregivers
      of patients with Alzheimer's disease. Among them, seven were the spouses (four of
      seven patients are men), and one was the daughter of a patient. In a clinical
      psychological environment, we asked each caregiver the same question: "How would
      you talk about living or having lived Alzheimer'disease?" Our response will only
      aim to support words of the participant whenever necessary, but will also propose
      in difficult and particularly challenging moments, the possibility of sharing to
      enable the participant to verbalize their emotions. RESULTS: The meeting with
      some caregivers evidenced the preservation of a particular relationship with the
      patient, relationship within which the caregiver perceives in return the
      unspeakable weight of a disease, which works silently. Alzheimer's disease
      induces psychological modifications and requires great investment by caregivers,
      which is grafted on an earlier relationship. We should not consider the
      modifications in a linear relationship patient-caregiver but in a circular
      relationship, which complicates the relation of the couple and makes it
      indecisive. The violence of the confrontation with this disease results from
      multiple factors: social representations, impact of the diagnosis, evolution of
      the disease, affectivity and permanent interactions, in spite of the non verbal
      communication of the patient, which associates a love story, behaviour disorders
      and the impact on the social circle. The family's responses are for example
      denial, overprotection, mothering and aggressiveness in caregiving in order to
      maintain the relationship. Becoming a caregiver is difficult because of the limit
      between professional and caregiver. Accompaniment is not a simple role of
      watching and caring. Because of the love, because of the strength of the
      communication which continues even in the absence of words, the investment
      remains massive and Alzheimer's disease opens a distance where the relationship,
      if it is perturbed, is none the less reactivated, and makes the accompaniment
      possible, however painful it may be.

PMID- 22137217
TI  - [Psychomotor agitation, pharmaceutical sedation and psychiatric emergency in
      psychotic patients].
AB  - Psychomotor agitation, very common among psychiatric emergencies, raises the
      question of pharmaceutical sedation, its indications, and its issues, notably
      with regard to the observance in postemergency. A new approach to sedation places
      it within its therapeutic aim and also takes into account the sometimes harmful
      impact on the course of the patient's care. A pretherapeutical, analysis both
      clinical and environmental is crucial. The time spent on the initial meeting and
      assessment is essential. The evolution of professional practices in mental health
      allows us to distinguish three kinds of sedation (vigilance, behaviour and
      psychical) that guide the choice and the mode of psychotropic drug use. The
      harmful effects of an ever-increasing use of sedation is debated. The use of
      atypical antipsychotics and injectable forms is argued. Early psychical sedation
      is preferable to the obsolete practice of vigilance sedation and to behavioural
      sedation with its limited indications. The use of excessive or prolonged sedation
      might have a detrimental effect on the care offered after psychiatric emergency
      treatment.

PMID- 22137218
TI  - [The contributions of the evidence-based medicine or how to optimize the
      management of major depressive disorder].
AB  - In the early 1980s, Evidence-Based Medicine (EBM) has been developed in the
      Department of Clinical Epidemiology at McMaster Medical School in Canada to meet
      the ever-increasing need to integrate publications in clinical practice. In this
      approach, we cannot ever consider that the evidence will replace clinical
      experience. The quality of scientific data is prioritized taking into account the
      methodological characteristics of studies. It takes time to learn and practice
      the method, which is often difficult in daily practice. The concept of
      "management recommendations" covers multiple realities. It can rely on the
      results of clinical trials (randomized, controlled or not...), the trends from
      the meta-analysis that attempt to "simplify" the field of literature or the
      Clinical Practice Guidelines. Meta-analysis should be used with caution. They do
      not preclude the need to use the data "sources", but they help the comparability
      of results and synthesis work. However it should be aware that this is a work of
      interpretation. The controversy over the action of antidepressants compared to
      placebo in depression according to the severity of the episode shows that a
      result depends on the included studies, the statistical technique used, but also
      how the results are reported. The international literature produced many
      recommendations in the management of depression. It is useful to refer to it as
      the meta-analysis because they provide an overall view of the current state of
      knowledge. We can regret the lack of recent French recommendations that could
      articulate the specifics of the French practice and data from the literature. The
      use of guidelines in clinical practice remains low in all fields of medicine.
      However improving the consideration of the recommendations is an important issue
      because it is associated with improved patient care. It remains to develop a
      collective strategy to implement them. The Evidence-Based Medicine is a major
      change in the everyday clinical practice. It may be insufficiently known and
      understood, seems too complex, time-consuming and therefore inapplicable. We have
      to mobilize our efforts to improve our practices.

PMID- 22137219
TI  - [Reticence towards electroconvulsive therapy: a study of 120 caregivers in a
      teaching hospital in Tunisia].
AB  - INTRODUCTION: Electroconvulsive therapy (ECT) is rarely practiced in Tunisia. We
      have tried to explain this lack of use by studying theoretical knowledge, the
      perception and the attitudes of health professionals towards ECT. METHODS: We
      conducted a survey in the region of Sfax in Tunisia. It included 120
      participants. The latter were divided into four groups, composed of 30 members,
      in order to compare them: group 1 (psychiatrists); group 2 (neurologists and
      anaesthetists); group 3 (psychiatric nurses); group 4 (paramedics in the
      neurological and anaesthesia wards). The surveyed people answered an auto
      questionnaire including essentially 16 items: 11 had binary answers (true or
      false) related to theoretical knowledge about ECT, and five others explored the
      perception and attitudes concerning this therapy. RESULTS: Concerning the items
      exploring theoretical knowledge, 67.5% of people were not able to answer, in
      conformity with the consensual scientific data, a minimum of 75% questions. The
      rates were significantly lower among the paramedics (P<0.001) and those who work
      outside the psychiatric wards (P=0.003). The answers of psychiatric caregivers
      were less frequently incorrect compared to those of non psychiatric ward workers.
      The latter more frequently thought that the psychiatrists easily resorted to ECT
      (P=0.003). The paramedics perceived, more frequently than doctors, the ECT as a
      violent therapeutic means (P=0.001), and more frequently refused to give their
      consent to apply ECT to a relative (P=0.044). The rate of doctors who refused to
      give their consent to apply ECT to a relative was statistically higher in group 2
      than in group 1 (P=0.017). Doctors with higher scores in theoretical knowledge,
      consent more frequently to apply ECT to a member of their families (P=0.001).
      DISCUSSION: The comparison of theoretical knowledge between the two groups of
      doctors (group 1 versus group 2) revealed significantly more frequent incorrect
      answers among non-psychiatrists. The latter more frequently had erroneous ideas:
      that ECT was performed without anaesthesia; that it wasn't possible to apply it
      to pregnant women, nor to people suffering from Parkinson's disease, nor as a
      preventive treatment of recurrence, and that the vital risk was higher with ECT
      than medical treatments. Compared to the caregivers of group 3, group 4 had
      significantly more frequent negative attitudes toward ECT; concerning the
      application without anaesthesia, the lack of tolerance and the over-mortality
      rate related to ECT. This therapy seems to create an apprehension and a reticence
      among health professionals, mainly the paramedics and the non-psychiatrists. The
      lack of valid scientific knowledge concerning ECT allows prejudiced ideas to
      tarnish the image of this therapy. CONCLUSION: Information and training would
      play a primordial role in the improvement of the perception and attitudes
      concerning ECT, and lower the reticence towards this therapy, which in spite of
      its proven efficacy, always maintains a pejorative image.

PMID- 22137220
TI  - [Psychiatric, psychological comorbidities of typical and atypical Charles-Bonnet
      syndrome].
AB  - OBJECTIVES: Charles-Bonnet syndrome (CBS) is conventionally defined by the
      presence of visual hallucinations in patients suffering from lowered visual
      acuity without having psychosis or dementia. Actually, it is a syndrome that
      interests many specialties, especially ophthalmology, geriatrics, neurology and
      psychiatry. "Atypical CBS" or "CBS plus" was introduced to designate any kind of
      visual hallucinations that could be considered as a CBS but accompanied by a low
      level of insight, a possible cognitive decline, other hallucinatory modalities
      etc. Since all patients suffering from CBS have to be psychiatrically evaluated,
      psychological and psychiatric implications of their syndrome have to be well
      understood in order to better manage them. These psychiatric and psychological
      implications are: the relationship between the CBS and dementia, the
      psychological reaction of the patients towards their hallucinations and
      psychiatric comorbidities that could be developed during the course of the
      syndrome. METHODS: A research via MEDLINE for all the articles published in
      French or in English between January 1999 and December 2009 was done using the
      following keywords Charles-Bonnet, psychiatric comorbidities and Charles-Bonnet
      syndrome, Charles-Bonnet syndrome and dementia, psychological reaction and
      Charles-Bonnet syndrome. RESULTS: Although some studies report an association
      between the CBS and dementia, the majority of these studies do not confirm this
      association and point towards an atypical initial presentation of the syndrome.
      The psychological reaction accompanying the visual hallucinations of the typical
      CBS is variable (mild distress, indifference, pleasure). Patients suffering from
      a typical CBS conserve a full insight during the course of the syndrome. A
      positive personal psychiatric history or a concomitant psychiatric disorder
      changes the clinical presentation of the syndrome. DISCUSSION: Our research
      allowed us to define the following diagnostic criteria for the atypical CBS: 1)
      diminished level or absence of insight towards the visual hallucinations; 2)
      presence of a mild cognitive decline; 3) presence of an atypical psychological
      reaction towards the visual hallucinations as in the case of a severe and
      prolonged stressful reaction; 4) presence of other hallucinatory modalities; 5)
      presence of a positive personal psychiatric history or a concomitant psychiatric
      disorder. Each patient suffering from CBS should be initially evaluated
      psychiatrically and neurologically in order to confirm or to eliminate the
      presence of the most common causes of visual hallucinations. In the presence of a
      lowered visual acuity and a conserved cognitive functioning, the typical CBS is
      diagnosed after eliminating more common disorders. Once this diagnosis is
      established, patients should be evaluated in order to rule out the presence of an
      atypical clinical presentation. CONCLUSION: Atypical CBS is a syndrome that could
      be eventually associated with dementia, accompanied with a major depressive
      disorder or another psychiatric disorder, or with vulnerability towards
      psychiatric disorders. Patients suffering from atypical CBS should be closely
      followed psychiatrically and neurologically. Patients suffering from the typical
      CBS should also benefit from a psychiatric follow-up, due to their multiple
      psychiatric vulnerability factors and their possible management with psychotropic
      drugs.

PMID- 22137222
TI  - Bullous pemphigoid: from the clinic to the bench.
AB  - Bullous pemphigoid (BP) constitutes the most frequent autoimmune subepidermal
      blistering disease. It is associated with autoantibodies directed against the BP
      antigens 180 (BP180, BPAG2) and BP230 (BPAG1-e). The pathogenicity of anti-BP180
      antibodies has been convincingly demonstrated in animal models. The clinical
      features of BP are extremely polymorphous. The diagnosis of BP critically relies
      on immunopathologic findings. The recent development of novel enzyme-linked
      immunosorbent assays has allowed the detection of circulating autoantibodies with
      relatively high sensitivity and specificity. Although potent topical steroids
      have emerged in the past decade as first-line treatment of BP, management of the
      disease may be challenging.

PMID- 22137223
TI  - Autoimmune bullous diseases associations.
AB  - The presence of one autoimmune disorder helps lead to the discovery of other
      autoimmune conditions. It is thought that diseases in which autoimmunity is a
      feature tend to be associated together more often than one can ascribe to chance.
      A variety of diseases have been implicated in the onset of intraepidermal and
      subepidermal autoimmune diseases. The presence of one autoimmune disease should
      alert the physician to watch for a second immunologic disorder. A list of
      autoimmune bullous diseases associations includes autoimmune bullous diseases,
      pemphigus, pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis
      (Duhring), linear immunoglobulin A disease, and multiple autoimmune syndrome.

PMID- 22137224
TI  - Ocular and oral mucous membrane pemphigoid (cicatricial pemphigoid).
AB  - Mucous membrane pemphigoid, a heterogeneous group of autoimmune blistering
      diseases, affects primarily the mucous membranes. Although oral and ocular
      mucosae can both be affected in a given patient, patients with involvement
      restricted to oral mucosae tend to have a benign outcome, whereas those with
      ocular disease commonly face treatment resistance, resulting in scarring and
      blindness. Diagnosis requires direct immunofluorescence microscopy to demonstrate
      a linear deposition of immunoglobulin (Ig) G or IgA, or complement component 3
      (C3), at the epithelial basement membrane. Although the target antigens vary,
      subsets of patients affected exclusively by oral and ocular mucosal diseases have
      autoantibodies targeting alpha-6 and beta-4 integrins, respectively.

PMID- 22137225
TI  - Linear immunoglobulin A bullous dermatosis.
AB  - Linear immunoglobulin A (IgA) bullous dermatosis, also known as linear IgA
      disease, is an autoimmune mucocutaneous disorder characterized by subepithelial
      bullae, with IgA autoantibodies directed against several different antigens in
      the basement membrane zone. Its immunopathologic characteristic resides in the
      presence of a continuous linear IgA deposit along the basement membrane zone,
      which is clearly visible on direct immunofluorescence. This disorder shows
      different clinical features and distribution when adult-onset of linear IgA
      disease is compared with childhood-onset. Diagnosis is achieved via clinical,
      histopathologic, and immunopathologic examinations. Two common therapies are
      dapsone and sulfapyridine, which reduce the inflammatory response and achieve
      disease remission in a variable period of time.

PMID- 22137226
TI  - Pemphigoid gestationis.
AB  - Pemphigoid gestationis is a rare autoimmune subepidermal bullous dermatosis that
      occurs during pregnancy and postpartum. Diagnosis is made on the basis of the
      presence of a subepidermal vesicle on routine histologic examination and of
      linear deposition of complement along the basement membrane zone of perilesional
      skin. The disorder is accompanied by severe pruritus and polymorphous bullous
      skin lesions. Clinical diagnosis is confirmed by histology and positive cutaneous
      immunofluorescence and immunoelectron microscopy tests (linear deposition of C3,
      with or without immunoglobulin G, along the basement membrane zone, within the
      lamina lucida, and localized to the proximal part of anchoring filaments of the
      epidermal fragment of salt-split skin). Enzyme-linked immunosorbent assay for
      pemphigoid gestationis antibody (BP180) is commercially available. If local
      treatment fails, systemic corticosteroid therapy should be administered. Oral
      corticosteroids are the therapeutic mainstay in pregnancy and postpartum. The
      prognosis is good for mother and child, except that there is a risk of preterm
      delivery and of moderate fetal growth restriction. Recurrence is possible during
      subsequent pregnancies. There is no significant maternal morbidity or mortality.

PMID- 22137227
TI  - Dermatitis herpetiformis.
AB  - Dermatitis herpetiformis (DH) is a chronic, polymorphic, pruritic skin disease
      that develops mostly in patients with latent gluten-sensitive enteropathy. DH
      patients usually present with skin manifestations only and are not aware of the
      underlying small-bowel problems. Owing to the granular immunoglobulin (Ig) A
      deposition at the tips of the papillary dermis and to the subepidermal blister
      formation associated with neutrophilic accumulations underlying the basement
      membrane, DH is considered to be an autoimmune blistering disease. Contrary to
      the other bullous disorders, DH patients have no circulating autoantibodies
      binding to the cutaneous basement membrane components or to other adherent
      structures of the skin, but they have gluten-induced IgA autoantibodies against
      transglutaminase (TG) 2 and TG3. The serum IgA against tissue TG2 is a most
      specific and sensitive serologic marker of gluten-sensitive enteropathy and is
      equivalent to the perviously described IgA endomysium antibodies. DH could be a
      cutaneous IgA-epidermal TG3 immunocomplex disease, developing only in a few
      patients with gluten-sensitive enteropathy as a second gluten-dependent disease.
      The main treatment of DH today is a strict, life-long gluten-free diet. Untreated
      DH patients should be regularly monitored for malabsorption and lymphomas.
      Associated autoimmune diseases are more common among DH patients. Family
      screening for gluten sensitivity is also strongly suggested.

PMID- 22137229
TI  - Inherited epidermolysis bullosa: new diagnostic criteria and classification.
AB  - Epidermolysis bullosa (EB) is a group of inherited, mechanobullous disorders
      caused by mutations in various structural proteins in the skin. There have been
      several advances in the classification of EB since it was first introduced in the
      late 19th century. We now recognize four major types of EB, depending on the
      location of the target proteins and level of the blisters: EB simplex
      (epidermolytic), junctional EB (lucidolytic), dystrophic EB (dermolytic), and
      Kindler syndrome (mixed levels of blistering). This contribution will summarize
      the most recent classification and discuss the molecular basis, target genes, and
      proteins involved. We have also included new subtypes, such as autosomal dominant
      junctional EB and autosomal recessive EB due to mutations in the dystonin (DST)
      gene, which encodes the epithelial isoform of bullouspemphigoid antigen 1. The
      main laboratory diagnostic techniques-immunofluorescence mapping, transmission
      electron microscopy, and mutation analysis-will also be discussed. Finally, the
      clinical characteristics of the different major EB types and subtypes will be
      reviewed.

PMID- 22137230
TI  - Immunosuppressive therapy for autoimmune bullous diseases.
AB  - Adjuvant immunosuppressive drugs are widely used to minimize corticosteroid
      related adverse effects in the short-term and long-term management of cautoimmune
      bullous diseases. In bullous pemphigoid and pemphigus vulgaris, azathioprine and
      mycophenolate mofetil seem to be equally effective when used in combination with
      oral corticosteroids, but mycophenolate mofetil is less myelosuppressive and
      hepatotoxic. Due to a better safety profile, mycophenolate mofetil or enteric
      coated mycophenolate sodium may gradually replace azathioprine as the first-line
      adjuvant of choice in the treatment of moderate to severe autoimmune bullous
      diseases, including epidermolysis bullosa acquisita and cicatricial pemphigoid.
      Cyclophosphamide still has a place in the treatment of severe relapsing
      autoimmune bullous diseases. Continuous oral cyclophosphamide provides optimal
      immunosuppression, but it also produces the highest cumulative dose. Several
      pulsed cyclophosphamide regimens have, therefore, been developed and are reported
      to be effective in severe forms of pemphigus. Randomized controlled studies are
      needed to compare the efficacy and safety of cyclophosphamide with newer
      treatment options, such as rituximab and immunoapheresis, and to define optimal
      dose ranges and duration of available immunosuppressive treatments in different
      stages of autoimmune bullous diseases.

PMID- 22137228
TI  - Epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is a rare, acquired, chronic subepidermal
      bullous disease of the skin and mucosa characterized by autoantibodies to type
      VII collagen (C7) structures, a major component of anchoring fibrils, which
      attach the epidermis to the dermis. EBA patients have tissue-bound and
      circulating antitype C7 autoantibodies that attack type C7 and result in a
      reduction or perturbation of normally functioning anchoring fibrils. Patients
      with EBA have skin fragility, blisters, erosions, scars, milia, and nail loss,
      all features reminiscent of genetic dystrophic epidermolysis bullosa. These
      immunoglobulin G antitype C7 antibodies are pathogenic, because when they are
      injected into mice, the mice develop an EBA-like blistering disease. In addition
      to the classical mechanobullous presentation, EBA also has several other distinct
      clinical syndromes similar to bullous pemphigoid, Brunsting-Perry pemphigoid, or
      cicatricial pemphigoid. Although treatment for EBA is often unsatisfactory, some
      therapeutic success has been achieved with colchicine, dapsone, plasmapheresis,
      photopheresis, infliximab, and intravenous immunoglobulin.

PMID- 22137231
TI  - Current therapy of the pemphigus group.
AB  - Treatment of pemphigus patients is still challenging and, in some cases,
      conventional therapy with systemic corticosteroids in combination with adjuvant
      corticosteroid-sparing immunosuppressive drugs is not sufficient to induce
      clinical remission. More recently, high-dose intravenous immunoglobulins,
      immunoadsorption, and the monoclonal anti-CD20 antibody, rituximab, have been
      established as additional successful therapeutic options. This contribution
      covers both conventional therapies and most current treatment strategies for
      pemphigus.

PMID- 22137232
TI  - Treatment of subepidermal immunobullous diseases.
AB  - The subepidermal immunobullous diseases are a group of autoimmune blistering
      disorders of the skin and mucous membranes that share the common features of
      autoantibody deposition and blister formation at the dermal-epidermal junction or
      basement membrane. This group includes bullous pemphigoid, linear IgA disease,
      dermatitis herpetiformis, and epidermolysis bullosa acquisita, among others.
      Although these disorders share some common features, each disease is unique in
      its clinical presentation, histopathology, and immunofluorescence patterns, which
      allows for accurate diagnosis and disease-specific treatment strategy. Treatment
      of these disorders is complex and requires expert knowledge of disease
      pathogenesis. We review common treatment approaches for each of these disorders.

PMID- 22137234
TI  - Severity score indexes for blistering diseases.
AB  - Scoring systems are used to assess the severity of a disease and the response to
      treatment. The main severity scoring indexes are the Autoimmune Bullous Skin
      Disorder Intensity Score (ABSIS) and the Pemphigus Disease Area Index (PDAI).
      They have been validated and are already used in the evaluation of pemphigus and
      in clinical trials. They quantify disease severity by performing a global
      assessment of all lesions. In recent years, other severity scoring systems have
      been developed for pemphigus and other autoimmune blistering diseases.

PMID- 22137233
TI  - Quality of life in patients with bullous dermatoses.
AB  - Genetic and acquired bullous dermatoses can severely affect multiple domains of a
      patient's quality of life (QOL). Integrating formal evaluation of QOL into the
      clinical evaluation of patients facilitates an objective assessment of disease
      severity, mapping of disease trajectory, and captures therapeutic intervention
      outcomes. There have been 5 studies evaluating QOL in autoimmune dermatoses and 4
      studies reviewing QOL in the genodermatoses. All literature to date indicates a
      significant disease burden in this setting. The development of formal QOL
      instruments has facilitated quantification of QOL deficits in this arena and
      offers promising tools for patient assessment in the future.

PMID- 22137235
TI  - Autoimmune bullous diseases in childhood.
AB  - Autoimmune blistering disorders are a heterogeneous group of diseases that result
      from autoantibodies generated against target antigens found in the skin and
      mucous membranes. This process leads to a variety of disruptions in keratinocyte
      adhesion and cellular integrity, resulting in fluid accumulation and development
      of blisters. Physicians should have an appreciation and understanding of
      autoimmune blistering disorders in the pediatric population when formulating a
      differential diagnosis of a patient who presents with skin blistering. Early
      detection and discrimination between the varied autoimmune blistering disorders
      can change the course of treatment and outcome. Due to the similarity in clinical
      presentation among different diseases within this category, histopathologic
      evaluation and, especially, immunofluorescence studies are necessary to establish
      the definitive diagnosis.

PMID- 22137236
TI  - Effective communications using key messaging.

PMID- 22137237
TI  - 2011 consensus statement on endomyocardial biopsy from the Association for
      European Cardiovascular Pathology and the Society for Cardiovascular Pathology.
AB  - The Association for European Cardiovascular Pathology and the Society for
      Cardiovascular Pathology have produced this position paper concerning the current
      role of endomyocardial biopsy (EMB) for the diagnosis of cardiac diseases and its
      contribution to patient management, focusing on pathological issues, with these
      aims: * Determining appropriate EMB use in the context of current diagnostic
      strategies for cardiac diseases and providing recommendations for its rational
      utilization * Providing standard criteria and guidance for appropriate tissue
      triage and pathological analysis * Promoting a team approach to EMB use,
      integrating the competences of pathologists, clinicians, and imagers.

PMID- 22137238
TI  - Comparison of a novel bone-tendon allograft with a human dermis-derived patch for
      repair of chronic large rotator cuff tears using a canine model.
AB  - PURPOSE: This study tested a bone-tendon allograft versus human dermis patch for
      reconstructing chronic rotator cuff repair by use of a canine model. METHODS:
      Mature research dogs (N = 15) were used. Radiopaque wire was placed in the
      infraspinatus tendon (IST) before its transection. Three weeks later, radiographs
      showed IST retraction. Each dog then underwent 1 IST treatment: debridement (D),
      direct repair of IST to bone with a suture bridge and human dermis patch
      augmentation (GJ), or bone-tendon allograft (BT) reconstruction. Outcome measures
      included lameness grading, radiographs, and ultrasonographic assessment. Dogs
      were killed 6 months after surgery and both shoulders assessed biomechanically
      and histologically. RESULTS: BT dogs were significantly (P = .01) less lame than
      the other groups. BT dogs had superior bone-tendon, tendon, and tendon-muscle
      integrity compared with D and GJ dogs. Biomechanical testing showed that the D
      group had significantly (P = .05) more elongation than the other groups whereas
      BT had stiffness and elongation characteristics that most closely matched normal
      controls. Radiographically, D and GJ dogs showed significantly more retraction
      than BT dogs (P = .003 and P = .045, respectively) Histologically, GJ dogs had
      lymphoplasmacytic infiltrates, tendon degeneration and hypocellularity, and poor
      tendon-bone integration. BT dogs showed complete incorporation of allograft bone
      into host bone, normal bone-tendon junctions, and well-integrated allograft
      tendon. CONCLUSIONS: The bone-tendon allograft technique re-establishes a
      functional IST bone-tendon-muscle unit and maintains integrity of repair in this
      model. CLINICAL RELEVANCE: Clinical trials using this bone-tendon allograft
      technique are warranted.

PMID- 22137239
TI  - Modified dendrimer cross-linked collagen-based matrices.
AB  - Dendrimer cross-linking has been achieved with pepsin digested over 80% type-I
      bovine collagen to create strong hydrogels with good cell compatibility. Herein
      we investigate the use of commercially available collagen-based products with the
      dendrimer cross-linking technology. Specifically PureCol((r)) (PC), a 97% bovine
      type-I collagen, human collagen (HC) and human extracellular matrix (hECM) were
      concentrated, and then cross-linked with polypropyleneimine octaamine generation
      two dendrimers using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide
      hydrochloride (EDC) and N-hydroxysuccinimide (NHS) chemistry. PC gels with 30 and
      20 mg/ml bovine collagen were fabricated, and despite similar concentrations to
      >80% type-I bovine collagen dendrimer cross-linked gels (CG), PC gels
      demonstrated increased swelling and decreased stability, as determined with
      collagenase digestion. The highly purified bovine (PC) and human sourced-collagen
      (HC) gels were similar in performance, but not as stable as the CG gels, which
      may correlate to the manufacturer's collagen purification and storage. Finally,
      the addition of hECM components to PC to create PC-hECM gels, resulted in a
      looser gel network, compared to heparinized dendrimer cross- linked bovine >80%
      type-I collagen gels (CHG). However, all collagen-based gels supported 3T3
      fibroblast cell growth over 4 days, indicating these gels may be suitable for
      tissue-engineering applications. 

PMID- 22137240
TI  - Calcium and other signalling pathways in neuroendocrine regulation of somatotroph
      functions.
AB  - Relative to mammals, the neuroendocrine control of pituitary growth hormone (GH)
      secretion and synthesis in teleost fish involves numerous stimulatory and
      inhibitory regulators, many of which are delivered to the somatotrophs via direct
      innervation. Among teleosts, how multifactorial regulation of somatotroph
      functions are mediated at the level of post-receptor signalling is best
      characterized in goldfish. Supplemented with recent findings, this review focuses
      on the known intracellular signal transduction mechanisms mediating the ligand-
      and function-specific actions in multifactorial control of GH release and
      synthesis, as well as basal GH secretion, in goldfish somatotrophs. These include
      membrane voltage-sensitive ion channels, Na(+)/H(+) antiport, Ca(2+) signalling,
      multiple pharmacologically distinct intracellular Ca(2+) stores, cAMP/PKA, PKC,
      nitric oxide, cGMP, MEK/ERK and PI3K. Signalling pathways mediating the major
      neuroendocrine regulators of mammalian somatotrophs, as well as those in other
      major teleost study model systems are also briefly highlighted. Interestingly,
      unlike mammals, spontaneous action potential firings are not observed in goldfish
      somatotrophs in culture. Furthermore, three goldfish brain somatostatin forms
      directly affect pituitary GH secretion via ligand-specific actions on membrane
      ion channels and intracellular Ca(2+) levels, as well as exert isoform-specific
      action on basal and stimulated GH mRNA expression, suggesting the importance of
      somatostatins other than somatostatin-14.

PMID- 22137241
TI  - Pulsatile distention of the nondiseased and stenotic aortic valve annulus:
      analysis with electrocardiogram-gated computed tomography.
AB  - BACKGROUND: Knowledge of the dynamic changes of the aortic valve (AV) annulus may
      aid in the sizing and design of transcatheter valve prostheses. We assessed AV
      annulus distention in patients without AV disease and with severe AV stenosis
      (AS) using computed tomography (CT). METHODS: Electrocardiogram-gated multislice
      CT scans of 15 patients without AV disease (age 53+/-12 years) and 20 patients
      with severe AS (age 81+/-6 years) were analyzed. Images in plane with the AV
      annulus were reconstructed for every 10% to 12.5% of the cardiac cycle. With the
      use of dedicated software the annulus was segmented. In all phases of the cardiac
      cycle the area was measured, as were the maximum radius (Rmax) and minimum radius
      (Rmin) of an ellipse fitted around the segmented lumen. The asymmetry ratio was
      defined as Rmax/Rmin. Direct comparison of both groups was not possible because
      age and scan protocols were confounding factors. RESULTS: The mean change of the
      area, Rmax, and Rmin was 122+/-33 mm2, 1.8+/-0.7 mm, and 2.4+/-0.5 mm in the
      patients with nondiseased annulus and 98+/-52 mm2, 1.4+/-0.7 mm, and 1.9+/-0.8 mm
      in those with AS. The mean asymmetry ratio was 1.3+/-0.1, indicating an elliptic
      annulus. Both the asymmetry ratio and the area changed significantly over the
      cardiac cycle (p<0.001). CONCLUSIONS: With the use of CT and postprocessing
      software, significant area and radius changes during the cardiac cycle were
      demonstrated in both the nondiseased annulus and the stenotic annulus. This
      finding may help selection of the optimal size in patients undergoing AV
      implantation and also aid in prosthesis design.

PMID- 22137242
TI  - Longer blood storage is associated with suboptimal outcomes in high-risk
      pediatric cardiac surgery.
AB  - BACKGROUND: The negative effects of long-term storage of allogeneic red blood
      cells (RBCs) on outcomes in adult cardiac surgery have been established, but
      evidence of a similar effect in pediatric cardiac surgery is limited. METHODS:
      The weighted average duration of storage for RBC units used in 1,225 pediatric
      cardiac operations was determined. Operations were divided into high RBC use
      (more than 4 units or more than 150 mL/kg) or low RBC use. For both categories,
      associations between storage duration and surgical outcomes, adjusted for
      relevant patient characteristics, were evaluated. RESULTS: High RBC use was
      associated with higher surgical complexity. Storage duration for patients who
      received low RBC volumes was not associated with surgical outcomes. For patients
      with high RBC transfusion volumes, longer storage duration (per day) was
      associated with higher odds of bleeding complications (odds ratio 1.029, p=0.07),
      renal insufficiency (odds ratio 1.085, p=0.001), higher inotrope score after
      surgery (12 to 24 hours +0.08, p=0.002; 24 to 48 hours +0.07, p<0.001), greater
      chest tube drainage (24 hours +1.5 mL/kg, p<0.001), longer postoperative
      hospitalization (+0.3 days p=0.02), and increased in-hospital mortality (odds
      ratio 1.054, p=0.03). Effects of RBC transfusions on postoperative bleeding were
      greatest for storage duration longer than 14 days. CONCLUSIONS: The freshest RBC
      units available should be used for pediatric cardiac operations expected to
      require more than 4 units or more than 150 mL/kg of allogeneic RBC transfusions,
      with no units more than 14 days old being transfused whenever possible.

PMID- 22137243
TI  - Model of health? Distributed preparedness and multi-agency interventions
      surrounding UK regional airports.
AB  - The liberalisation of the European aviation sector has multiplied paths of entry
      into the United Kingdom (UK) for the international traveller. These changing
      mobilities necessitate a reconceptualisation of the border as a series of
      potentially vulnerable nodes occurring within, and extending beyond, national
      boundaries. In this paper, we consider the border through the lens of port
      health, the collective term for various sanitary operations enacted at
      international transport terminals. In the UK, a critical player in the oversight
      of port health is the Health Protection Agency (HPA), which became a non
      Departmental public body in 2005. A major part of port health is preparedness, a
      set of techniques aimed at managing, and responding to, emergencies of public
      health concern. More recently, certain jurisdictions have embarked on public
      health preparedness work across a number of different geographical scales. Using
      methods pioneered by the military, this form of 'distributed preparedness' is of
      increased interest to social science and medical scholars. With reference to case
      studies conducted in localities surrounding two UK regional airports following
      the 2009-10 H1N1 influenza pandemic, we consider the extent to which distributed
      preparedness as a concept and a set of practices can inform current debates - in
      the UK, and beyond - concerning interventions at the border 'within'.

PMID- 22137244
TI  - How does the business cycle affect eating habits?
AB  - As economic expansions raise employment and wages, associated shifts in income
      and time constraints would be expected to also impact individuals' health. This
      study utilizes information from the US Behavioral Risk Factor Surveillance System
      (1990-2009) to explore the relationship between the state unemployment rate and
      the consumption of various healthy and unhealthy foods in the United States.
      Estimates, based on fixed effects methodologies, indicate that unemployment is
      associated with reduced consumption of fruits and vegetables and increased
      consumption of "unhealthy" foods such as snacks and fast food. Heterogeneous
      responses are also identified through detailed sample stratifications and by
      isolating the effect for those predicted to be at highest risk of unemployment
      based on their socioeconomic characteristics. Among individuals predicted to be
      at highest risk of being unemployed, a one percentage point increase in the
      resident state's unemployment rate is associated with a 3-6% reduction in the
      consumption of fruits and vegetables. The impact is somewhat higher among
      younger, low-educated, and married adults. Supplementary analyses also explore
      specific mediating pathways, and point to reduced family income and adverse
      mental health as significant channels underlying the procyclical nature of
      healthy food consumption.

PMID- 22137245
TI  - Five years later: recovery from post traumatic stress and psychological distress
      among low-income mothers affected by Hurricane Katrina.
AB  - Hurricane Katrina, which struck the Gulf Coast of the United States in August
      2005, exposed area residents to trauma and extensive property loss. However,
      little is known about the long-run effects of the hurricane on the mental health
      of those who were exposed. This study documents long-run changes in mental health
      among a particularly vulnerable group-low income mothers-from before to after the
      hurricane, and identifies factors that are associated with different recovery
      trajectories. Longitudinal surveys of 532 low-income mothers from New Orleans
      were conducted approximately one year before, 7-19 months after, and 43-54 months
      after Hurricane Katrina. The surveys collected information on mental health,
      social support, earnings and hurricane experiences. We document changes in post
      traumatic stress symptoms (PTSS), as measured by the Impact of Event Scale
      Revised, and symptoms of psychological distress (PD), as measured by the K6
      scale. We find that although PTSS has declined over time after the hurricane, it
      remained high 43-54 months later. PD also declined, but did not return to pre
      hurricane levels. At both time periods, psychological distress before the
      hurricane, hurricane-related home damage, and exposure to traumatic events were
      associated with PTSS that co-occurred with PD. Hurricane-related home damage and
      traumatic events were associated with PTSS without PD. Home damage was an
      especially important predictor of chronic PTSS, with and without PD. Most
      hurricane stressors did not have strong associations with PD alone over the short
      or long run. Over the long run, higher earnings were protective against PD, and
      greater social support was protective against PTSS. These results indicate that
      mental health problems, particularly PTSS alone or in co-occurrence with PD,
      among Hurricane Katrina survivors remain a concern, especially for those who
      experienced hurricane-related trauma and had poor mental health or low
      socioeconomic status before the hurricane.

PMID- 22137246
TI  - Reply: PGD and aneuploidy screening for 24 chromosomes by genome-wide SNP
      analysis: a responsible path towards greater utility.

PMID- 22137247
TI  - Hepatic aminotransferases of normal and IUGR fetuses in cord blood at birth.
AB  - BACKGROUND: The accepted standard for assessing the wellbeing of the newborn is
      the Apgar score and blood gas analysis. However, the prediction of neonatal
      morbidity or mortality is limited. In small-for-gestation (SGA) fetuses at 18-38
      weeks of gestation, pO(2) is <5th centile both in the umbilical artery and vein
      in 30%. In a previous study in singleton term neonates cardiac specific enzymes
      (B-type natriuretic peptide, BNP and cardiac troponin T, cTnT) are increased in
      growth-restricted fetuses compared with normals. AIMS: To test the hypothesis,
      that fetuses with intra uterine growth restriction (IUGR) have elevated AST (GOT)
      and ALT (GPT) aminotransferases as a result of hypoxic liver cell injury, and to
      establish references ranges. STUDY DESIGN: Prospective cohort study, serum of
      umbilical artery (n=156) and vein (n=180), 599 normal singletons at 37(+0)
      42(+0)weeks, neonates with IUGR (n=41), analysis for pH, birthweight and maternal
      weight, spontaneous vs cesarean section, vein vs artery and for the sex. OUTCOME
      MEASURES: Aspartate aminotransferase (AST, GOT) and Alanine aminotransferase
      (ALT, GPT) were measured in normals and IUGR neonates. RESULTS: Neonates with
      IUGR (n=41) had AST values that were not different from the reference group, but
      had significantly lower ALT (-1.49, 95% CI -1.98 to -1.00 vs 0.14, 95% CI -0.42
      0.13), (p<0.001), (Fig. 3). CONCLUSIONS: In neonates with IUGR, hypoxic hepatic
      injury markers in cord blood were not elevated. Rather, a substantially reduced
      ALT suggests a down-regulated hepatic activity.

PMID- 22137248
TI  - Introductory editorial: prenatal diagnosis and fetal surgery.

PMID- 22137249
TI  - Influence of light on growth, fumonisin biosynthesis and FUM1 gene expression by
      Fusarium proliferatum.
AB  - Fumonisins are a group of mycotoxins, mainly found in maize and maize-based food
      and feed, associated with several diseases in animals. The impact of these toxins
      on the economy and health worldwide has driven several efforts to clarify the
      role of environmental factors that can influence fumonisin biosynthesis by the
      toxigenic species. We analyzed the influence of light of varying wavelength on
      growth and fumonisin biosynthesis by the fungus Fusarium proliferatum ITEM 1719.
      Light in general had a positive influence on growth, with a mean increase of the
      grow rate of about 40% under light exposure in comparison to the dark incubation.
      Wavelengths from both sides of the spectrum, from long (627 nm) to short
      wavelength (470-455 nm) had a stimulating effect on fumonisin biosynthesis
      compared to the dark incubation: fumonisins B(1) (FB(1)) and B(2) (FB(2))
      production increased of about 40 fold under red, 35 fold under blue, 20 fold
      under royal blue, 10 fold under green, 5 fold under yellow and 3 fold under white
      light in comparison to the dark incubation. The transcriptional regulation of the
      FUM1 fumonisin biosynthesis gene was analyzed by Real time reverse transcriptase
      PCR quantification, revealing a correlation between fumonisin biosynthesis and
      gene expression. These findings show a role of light on the growth and the
      modulation of fumonisin biosynthesis and provide new information on the
      physiology of an important toxigenic maize pathogen.

PMID- 22137250
TI  - Identification and characterization of Lactobacillus florum strains isolated from
      South African grape and wine samples.
AB  - A total of 213 strains of lactic acid bacteria were examined in this study. Among
      these, 30 strains previously isolated from South African grape and wine samples
      remained unidentified. The identification of these isolates was performed by
      BLAST and phylogenetic analyses of 16S rDNA gene sequences, which indicated that
      the isolates belonged to Lactobacillus florum. In this work, we also designed a
      discriminative species-specific primer FLOR targeting the 16S rDNA gene of Lb.
      florum. The validity and specificity of this primer was confirmed. Of particular
      interest in this study was to further evaluate the identified strains for the
      presence of genes encoding enzymes of oenological relevance. Reference strains
      included three flower-associated Lb. florum (F9-1(T), F9-2 and F17) and two
      Lactobacillus lindneri (AWRI B530 and DSM 20691) strains. Lb. lindneri strains
      were incorporated as being the closest relatives of Lb. florum. PCR detection
      results revealed that all Lb. florum strains and Lb. lindneri AWRI B530 (grape
      isolate) possessed the majority of the tested genes relative to DSM 20691 (beer
      isolate); these enzyme-encoding genes included malolactic enzyme, peptidases
      (PepC, PepI, PepN), citrate lyase (alpha- and beta-subunits), phenolic acid
      decarboxylase and arginine deiminase pathway enzymes (arginine deiminase and
      ornithine transcarbamylase). Sequence verification of PCR-generated fragments was
      performed by sequencing. The sequence data were used to construct the
      phylogenetic trees, which indicated that our Lb. florum isolates cluster with
      other Lb. florum strains of flower origin but rather distinct from other LAB
      species, with Lb. lindneri being the next closest species.

PMID- 22137251
TI  - Safety assessment of Zanthoxylum alatum Roxb. essential oil, its antifungal,
      antiaflatoxin, antioxidant activity and efficacy as antimicrobial in preservation
      of Piper nigrum L. fruits.
AB  - The investigation deals with antifungal, antiaflatoxin and antioxidant efficacy
      of Zanthoxylum alatum Roxb. essential oil (EO), its two major constituents and
      their comparison with five commonly used organic acid preservatives. The chemical
      profile of EO, characterized through GC and GC-MS analysis, revealed linalool
      (56.10%) and methyl cinnamate (19.73%) as major components. The EO, linalool and
      methyl cinnamate completely inhibited the growth of a toxigenic strain of A.
      flavus (LHP-10) as well as aflatoxin B(1) secretion at different concentrations.
      Methyl cinnamate was found to be more efficacious than EO, linalool and five
      organic acid preservatives, showing antifungal and antiaflatoxigenic efficacy at
      a low concentration (0.6 MUl/ml) and the nature of its toxicity was fungicidal.
      However, EO showed strong antioxidant activity with an IC(50) value at 5.6
      MUl/ml. Moreover, EO was found to have negligible mammalian toxicity as its
      LD(50) value, determined through oral administration on mice, was calculated to
      be 6124MUl/kg body weight during safety profile assessment. During in vivo
      investigation on fruit systems, the Zanthoxylum EO, when tested as fumigant,
      provided 66.27% and 86.33% protection respectively at 1.25 MUl/ml and 2.5 MUl/ml
      against fungi infesting Piper nigrum L. fruits demonstrating its practical
      efficacy as a plant based antimicrobial for post harvest application.

PMID- 22137252
TI  - Head-to-head comparison of peak supine bicycle exercise echocardiography and
      treadmill exercise echocardiography at peak and at post-exercise for the
      detection of coronary artery disease.
AB  - BACKGROUND: Supine bicycle exercise (SBE) echocardiography and treadmill exercise
      (TME) echocardiography have been used for evaluation of coronary artery disease
      (CAD). Although peak imaging acquisition has been considered unfeasible with TME,
      higher sensitivity for the detection of CAD has been recently found with this
      method compared with post-TME echocardiography. However, peak TME
      echocardiography has not been previously compared with the more standardized peak
      SBE echocardiography. The aim of this study was to compare peak TME
      echocardiography, peak SBE echocardiography, and post-TME echocardiography for
      the detection of CAD. METHODS: A series of 116 patients (mean age, 61 +/- 10
      years) referred for evaluation of CAD underwent SBE (starting at 25 W, with 25-W
      increments every 2-3 min) and TME with peak and postexercise imaging acquisition,
      in a random sequence. Digitized images at baseline, at peak TME, after TME, and
      at peak SBE were interpreted in a random and blinded fashion. All patients
      underwent coronary angiography. RESULTS: Maximal heart rate was higher during
      TME, whereas systolic blood pressure was higher during SBE, resulting in similar
      rate-pressure products. On quantitative angiography, 75 patients had coronary
      stenosis (>=50%). In these patients, wall motion score indexes at maximal
      exercise were higher at peak TME (median, 1.45; interquartile range [IQR], 1.13
      1.75) than at peak SBE (median, 1.25; IQR, 1.0-1.56) or after TME (median, 1.13;
      IQR, 1.0-1.38) (P = .002 between peak TME and peak SBE imaging, P < .001 between
      post-TME imaging and the other modalities). The extent of myocardial ischemia
      (number of ischemic segments) was also higher during peak TME (median, 5; IQR, 2
      12) compared with peak SBE (median, 3; IQR, 0-8) or after TME (median, 2; IQR, 0
      4) (P < .001 between peak TME and peak SBE imaging, P < .001 between post-TME
      imaging and the other modalities). ST-segment changes in patients with CAD and
      normal baseline ST segments were higher during TME (median, 1 mm [IQR, 0-1.9 mm]
      vs 0 mm [IQR, 0-1.5 mm]; P = .006). The sensitivity of peak TME, peak SBE, and
      post-TME echocardiography for CAD was 84%, 75%, and 60% (P = .001 between post
      TME and peak TME echocardiography, P = .055 between post-TME and peak SBE
      echocardiography), with specificity of 63%, 80%, and 78%, respectively (P = NS)
      and accuracy of 77%, 77%, and 66%, respectively (P = NS). Peak TME
      echocardiography diagnosed multivessel disease in 27 of the 40 patients with
      stenoses in more than one coronary artery, in contrast to 17 patients with peak
      SBE imaging and 12 with post-TME imaging (P < .05 between peak TME imaging and
      the other modalities). Image quality was similar with the three techniques. The
      duration of the test was longer with SBE echocardiography (9.5 +/- 3.8 vs 7.6 +/-
      2.5 min, P < .001). CONCLUSIONS: During TME and SBE, patients achieve similar
      double products. Ischemia is more extensive and frequent with peak TME, which
      makes peak TME a more valuable exercise echocardiographic modality to increase
      sensitivity. However, peak SBE should be preferred to TME if the latter is
      performed with postexercise imaging acquisition.

PMID- 22137253
TI  - Strain, strain rate, and the force frequency relationship in patients with and
      without heart failure.
AB  - BACKGROUND: The aim of this study was to examine the effect of heart rate (HR) on
      indices of deformation in adults with and without heart failure (HF) who
      underwent simultaneous high-fidelity catheterization of the left ventricle to
      describe the force-frequency relationship. METHODS: Right atrial pacing to
      control HR and high-fidelity recordings of left ventricular (LV) pressure were
      used to inscribe the force-frequency relationship. Simultaneous two-dimensional
      echocardiographic imaging was acquired for speckle-tracking analysis. RESULTS:
      Thirteen patients with normal LV function and 12 with systolic HF (LV ejection
      fraction, 31 +/- 13%) were studied. Patients with HF had depressed isovolumic
      contractility and impaired longitudinal strain and strain rate. HR-dependent
      increases in LV+dP/dt(max), the force-frequency relationship, was demonstrated in
      both groups (normal LV function, baseline to 100 beats/min: 1,335 +/- 296 to
      1,564 +/- 320 mm Hg/sec, P < .0001; HF, baseline to 100 beats/min: 970 +/- 207 to
      1,083 +/- 233 mm Hg/sec, P < .01). Longitudinal strain decreased significantly
      (normal LV function, baseline to 100 beats/min: 18.0 +/- 3.5% to 10.8 +/- 6.0%, P
      < .001; HF: 9.4 +/- 4.1% to 7.5 +/- 3.4%, P < .01). The decrease in longitudinal
      strain was related to a decrease in LV end-diastolic dimensions. Strain rate did
      not change with right atrial pacing. CONCLUSIONS: Despite the inotropic effect of
      increasing HR, longitudinal strain decreases in parallel with stroke volume as
      load-dependent indices of ejection. Strain rate did not reflect the modest HR
      related changes in contractility; on the other hand, the use of strain rate for
      quantitative stress imaging is also less likely to be confounded by chronotropic
      responses.

PMID- 22137254
TI  - Prognostic value of exercise echocardiography in patients with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Although exercise echocardiography may assess left ventricular (LV)
      function and LV outflow tract (LVOT) gradients during exercise in patients with
      hypertrophic cardiomyopathy (HCM), its value for predicting outcomes has not been
      studied. The aim of this study was to determine whether exercise echocardiography
      predicts outcomes in patients with HCM. METHODS: LV function and LVOT gradients
      were evaluated during exercise echocardiography in 239 patients with HCM.
      RESULTS: Sixty patients (25.1%) had LVOT obstruction at rest, and 43 (18%)
      developed exercise-induced LVOT obstruction. The mean resting LV ejection
      fraction was 69 +/- 9%, and the mean resting wall motion score index was 1.00 +/-
      0.06. Wall motion abnormalities during exercise were seen in 19 patients (7.9%).
      During follow-up of 4.1 +/- 2.6 years, 19 patients had hard events (cardiac
      death, cardiac transplantation, appropriate discharge of a defibrillator, stroke,
      myocardial infarction, or hospitalization for heart failure), and 41 patients had
      composite end points of hard or soft events (including atrial fibrillation and
      syncope). Exercise wall motion abnormalities occurred in 31.5% of patients with
      hard events compared with 5.9% of patients without hard events (P < .001). After
      adjustment, LV wall thickness (hazard ratio [HR], 1.13; 95% confidence interval
      [CI], 1.05-1.21; P = .002), resting wall motion score index (HR, 21.59; 95% CI,
      2.38-196.1, P = .006), and metabolic equivalents (HR, 0.74; 95% CI, 0.63-0.88; P
      = .001) remained independent predictors of hard events. Change in wall motion
      score index was also independently associated with hard events (HR, 52.30; 95%
      CI, 3.81-718.5; P = .003) and with the composite end point (HR, 39.51; 95% CI,
      3.79-412.4; P = .002). LVOT obstruction was not associated with either end point.
      CONCLUSIONS: Assessment of exercise capacity and LV systolic function during
      exercise echocardiography may have a role in risk stratification of patients with
      HCM.

PMID- 22137255
TI  - Right-heart function related to the results of acute pulmonary vasodilator
      testing in patients with pulmonary arterial hypertension caused by connective
      tissue disease.
AB  - BACKGROUND: Acute pulmonary vasodilator testing is important for patients with
      pulmonary arterial hypertension, but little is known about the predictors of
      response to such testing. METHODS: Forty-eight patients (mean age, 41.3 +/- 11.6
      years; 91.7% women) with pulmonary arterial hypertension associated with
      connective tissue diseases who underwent right-heart catheterization and acute
      pulmonary vasodilator testing were prospectively recruited. Echocardiography was
      performed before and immediately after testing. RESULTS: There were 14 responders
      (29.2%) to acute pulmonary vasodilator testing. Responders had lower pulmonary
      vascular resistance, higher peak systolic velocity of the lateral tricuspid valve
      annulus (right ventricular [RV] S') and tricuspid annular plane systolic
      excursion, and smaller RV end-diastolic area. After vasodilator testing, mean
      pulmonary artery pressure and pulmonary vascular resistance decreased
      significantly in both groups, cardiac index increased significantly in
      responders, and RV function improved significantly in nonresponders. Receiver
      operating characteristic curve analysis identified an optimal cutoff value for RV
      S' of >=10.5 cm/sec to predict response, with sensitivity of 71% and specificity
      of 71%. There were more responders among patients with RV S' >= 10.5 cm/sec
      (45.5% vs 15.4%, P = .02). On multivariate logistic regression analysis, RV S' >=
      10.5cm/sec emerged as an independent predictor of response (odds ratio, 4.58; 95%
      confidence interval, 1.18-17.79; P = .02). CONCLUSIONS: Right-heart function is
      better in responders to acute pulmonary vasodilator testing than in nonresponders
      among patients with pulmonary arterial hypertension associated with connective
      tissue diseases, and pulmonary vasodilators may improve RV function in
      nonresponders and cardiac index in responders. RV S' is a simple and clinically
      useful tool for predicting the results of pulmonary vasodilator testing.

PMID- 22137256
TI  - Acute supplementation with eicosapentaenoic acid reduces platelet microparticle
      activity in healthy subjects.
AB  - BACKGROUND: Dietary supplementation with omega-3 fatty acids has been associated
      with reduced incidence in thrombotic events. In addition, administration of n-3
      polyunsaturated fatty acids (PUFAs) has been shown to rectify elevated platelet
      microparticle (MP) number and procoagulant activity in post myocardial infarction
      patients. However, it is unknown whether supplementation can alter these
      parameters in healthy individuals and if such effects are immediate or require
      long-term supplementation. We have previously demonstrated a gender-specific
      effect of LCn-3PUFA supplementation on platelet aggregation in healthy human
      subjects. Here we extend these findings to include the acute effects of
      supplementation with EPA- or DHA-rich oils on circulating MP levels and activity
      in healthy subjects. DESIGN: A placebo-controlled trial was conducted in healthy
      males and females (n=30). MP activity, MP levels and platelet aggregation were
      measured at 0 and 24 h postsupplementation with either a placebo or EPA- or DHA
      rich oil. RESULTS: Both EPA and DHA effectively reduced platelet aggregation at
      24 h postsupplementation relative to placebo (-13.3%, P=.006 and -11.9%, P=.016,
      respectively), but only EPA reduced MP activity (-19.4%, P=.003). When grouped by
      gender, males showed a similar reduction in both platelet aggregation and MP
      activity (-20.5%, P=.008; -22%, P=.008) following EPA, while females showed
      significantly reduced platelet aggregation (-13.7%, P=.04) but not MP activity
      after DHA only. CONCLUSION: EPA and DHA exert gender-dependent effects on
      platelet aggregation and platelet MP activity, but not on MP levels. With respect
      to thrombotic disease risk, males may benefit more from EPA supplementation.

PMID- 22137257
TI  - Intrauterine growth restriction leads to changes in sulfur amino acid metabolism,
      but not global DNA methylation, in Yucatan miniature piglets.
AB  - Intrauterine growth restriction (IUGR), in both animals and humans, has been
      linked to metabolic syndrome later in life. There has been recent evidence that
      perturbations in sulfur amino acid metabolism may be involved in this early
      programming phenomenon. Methionine is the precursor for cellular methylation
      reactions and for the synthesis of cysteine. It has been suggested that the
      mechanism behind the "fetal origins" of adult diseases may be epigenetic,
      involving DNA methylation. Because we have recently demonstrated the fetal
      origins phenomenon in Yucatan miniature swine, we hypothesized that sulfur amino
      acid metabolism is altered in IUGR piglets. In this study, metabolites and the
      activities of sulfur amino acid cycle enzymes were analyzed in liver samples of 3
      to 5-day-old runt (IUGR: 0.85+/-0.13 kg) and large (1.36+/-0.21 kg) Yucatan
      miniature pig littermates (n=6 pairs). The IUGR piglets had significantly lower
      specific and total activities of betaine-homocysteine methyltransferase (BHMT)
      and cystathionine gamma-lyase (CGL) than larger littermates (P<.05). Expression
      of CGL (but not BHMT) mRNA was also lower in IUGR piglets (P<.05). This low CGL
      reduced cysteine and taurine concentrations in IUGR pigs and led to an
      accumulation of hepatic cystathionine, with lower homocysteine concentrations.
      Methylation index and liver global DNA methylation were unaltered. Reduced
      prenatal growth in Yucatan miniature piglets impairs their remethylation capacity
      as well as their ability to remove cystathionine and synthesize cysteine and
      taurine, which could have important implications on long-term health outcomes of
      IUGR neonates.

PMID- 22137258
TI  - Biophysical and biochemical mechanisms by which dietary N-3 polyunsaturated fatty
      acids from fish oil disrupt membrane lipid rafts.
AB  - N-3 polyunsaturated fatty acids (PUFAs) from fish oil exert their functional
      effects by targeting multiple mechanisms. One mechanism to emerge in the past
      decade is the ability of n-3 PUFA acyl chains to perturb the molecular
      organization of plasma membrane sphingolipid/cholesterol-enriched lipid raft
      domains. These domains are nanometer-scale assemblies that coalesce to
      compartmentalize select proteins for optimal function. Here we review recent
      evidence on how n-3 PUFAs modify lipid rafts from biophysical and biochemical
      experiments from several different model systems. A central theme emerges from
      these studies. N-3 PUFA acyl chains display tremendous conformational flexibility
      and a low affinity for cholesterol and saturated acyl chains. This unique
      flexibility of n-3 PUFA acyl chains impacts the organization of inner and outer
      leaflet lipid rafts by disrupting acyl chain packing and molecular order within
      rafts. Ultimately, the disruption in raft organization has consequences for
      protein clustering and thereby signaling. Overall, elucidating the complex
      mechanisms by which n-3 PUFA acyl chains reorganize membrane architecture will
      enhance the translation of these fatty acids into the clinic for treating several
      diseases.

PMID- 22137259
TI  - Nutritional and supranutritional levels of selenate differentially suppress
      prostate tumor growth in adult but not young nude mice.
AB  - The inhibitory effect of oral methylseleninic acid or methylselenocysteine
      administration on cancer cell xenograft development in nude mice is well
      characterized; however, less is known about the efficacy of selenate and age on
      selenium chemoprevention. In this study, we tested whether selenate and duration
      on diets would regulate prostate cancer xenograft in nude mice. Thirty-nine
      homozygous NU/J nude mice were fed a selenium-deficient, Torula yeast basal diet
      alone (Se-) or supplemented with 0.15 (Se) or 1.0 (Se+) mg selenium/kg (as
      Na2SeO4) for 6 months in Experiment 1 and for 4 weeks in Experiment 2, followed
      by a 47-day PC-3 prostate cancer cell xenograft on the designated diet. In
      Experiment 1, the Se- diet enhanced the initial tumor development on days 11-17,
      whereas the Se+ diet suppressed tumor growth on days 35-47 in adult nude mice.
      Tumors grown in Se- mice were loosely packed and showed increased necrosis and
      inflammation as compared to those in Se and Se+ mice. In Experiment 2, dietary
      selenium did not affect tumor development or histopathology throughout the time
      course. In both experiments, postmortem plasma selenium concentrations in Se and
      Se+ mice were comparable and were twofold greater than those in Se- mice. Taken
      together, dietary selenate at nutritional and supranutritional levels
      differentially inhibit tumor development in adult, but not young, nude mice
      engrafted with PC-3 prostate cancer cells.

PMID- 22137260
TI  - Pretreatment with alanyl-glutamine suppresses T-helper-cell-associated cytokine
      expression and reduces inflammatory responses in mice with acute DSS-induced
      colitis.
AB  - T-helper (Th) cells play a major role in initiating and shaping the pathologic
      response in inflammatory bowel disease (IBD). Glutamine (GLN) is a nutrient with
      immune-modulating effects. This study investigated the effect of GLN on cytokine
      expressions and inflammatory responses of three subsets of Th cells in dextran
      sulfate sodium (DSS)-induced IBD. There were one normal control (NC) and two DSS
      groups. Mice in the DSS groups drank distilled water containing 3% DSS for 5
      days, whereas the NC group received distilled water. Mice in the G-DSS group were
      given intraperitoneal injection of 0.5 g GLN/kg/d for 3 days before receiving DSS
      water. The other DSS group (C-DSS) received an identical amount of amino acid
      solution without GLN. After induction of IBD, the mice were allowed to recover
      for 3 days and then were sacrificed. Blood and colon samples were collected for
      further analysis. The C-DSS group had higher percentages of blood interleukin
      (IL)-17A, IL-17F, IL-22, IL-4 and interferon-gamma than the NC group. The G-DSS
      group had lower Th1/Th17/Th2 cytokine expressions, which showed no differences
      from the NC group. Plasma haptoglobin, colon immunoglobin G and chemokine levels
      and myeloperoxidase activities were higher in the DSS groups than the NC group.
      These parameters were significantly lower in the G-DSS than the C-DSS group.
      These results suggest that pretreatment with GLN suppressed Th-associated
      cytokine expressions and may consequently reduce inflammatory mediator production
      and leukocyte infiltration into tissues, thus ameliorating the severity of acute
      DSS-induced colitis.

PMID- 22137261
TI  - Resveratrol induces Sirt1-dependent apoptosis in 3T3-L1 preadipocytes by
      activating AMPK and suppressing AKT activity and survivin expression.
AB  - Resveratrol is a natural polyphenolic compound with anti-inflammatory,
      antioxidant and neuroprotective properties, and it serves as a chemopreventive
      and chemotherapeutic agent. However, only very limited data have been obtained
      regarding the effects of resveratrol on preadipocytes, and the mechanisms of
      these effects remain largely unknown. In this study, murine 3T3-L1 preadipocytes
      were incubated with resveratrol, and cell apoptosis was investigated. Resveratrol
      caused S-phase arrest to inhibit cell proliferation and significantly increased
      the lactate dehydrogenase leaking ratio. Hoechst 33258 staining and transmission
      electron microscopy revealed the ultrastructural changes in nuclear chromatins of
      apoptotic cells. Furthermore, resveratrol activated the mitochondrial signaling
      with decreases in the mitochondrial membrane potential, cytochrome c release and
      the activation of caspase 9 and caspase 3. Resveratrol treatment also increased
      the protein level of Sirt1. By using small interfering RNAs of Sirt1, adenosine
      monophosphate-activated protein kinase (AMPK) alpha, survivin and the AMPK
      agonist (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside) and specific
      inhibitors for protein kinase B (AKT) or caspases, it was demonstrated that
      activation of Sirt1 inhibited AKT activation and further decreased the expression
      of survivin. It could also increase AMPK activation. Both signaling pathways
      activated mitochondrion-mediated pathway. Our findings clarified the apoptotic
      effects of resveratrol in 3T3-L1 preadipocytes and revealed the involved pathway
      including AMPK, AKT and survivin, suggesting its potential therapeutic
      application in the treatment or prevention of obesity and related metabolic
      symptoms.

PMID- 22137263
TI  - Lycopene and the LXRalpha agonist T0901317 synergistically inhibit the
      proliferation of androgen-independent prostate cancer cells via the PPARgamma
      LXRalpha-ABCA1 pathway.
AB  - In our previous study, we demonstrated that lycopene can inhibit the
      proliferation of androgen-dependent prostate LNCaP cancer cells through the
      activation of the peroxisome proliferator-activated receptor gamma (PPARgamma)
      liver X receptor alpha (LXRalpha)-ATP-binding cassette transporter 1 (ABCA1)
      pathway. However, it is still unclear whether lycopene possesses similar effects
      in androgen-independent prostate cancer cells DU145 and PC-3. As lycopene
      inhibited the proliferation of both cell types to a similar extent, we chose
      DU145 cells for most of the subsequent studies. We show that lycopene
      significantly increased protein and mRNA expression of PPARgamma, LXRalpha and
      ABCA1 and cholesterol efflux (i.e., decreased cellular cholesterol and increased
      cholesterol in culture medium). Lycopene (10 MUM) in the presence of a specific
      antagonist of PPARgamma (GW9662) or of LXRalpha (GGPP) restored the proliferation
      of DU145 cells and significantly suppressed lycopene-induced protein and mRNA
      expression of PPARgamma and LXRalpha and cholesterol efflux. Liver X receptor
      alpha knockdown by siRNA against LXRalpha significantly promoted the
      proliferation of DU145 cells, whereas si-LXRalpha knockdown followed by
      incubation with lycopene (10 MUM) restored the proliferation to the control
      level. Furthermore, lycopene in combination with the LXRalpha agonist T0901317
      exhibited synergistic effects on cell proliferation and protein expression of
      PPARgamma, LXRalpha and ABCA1. These results demonstrate that lycopene can
      inhibit DU145 cell proliferation via PPARgamma-LXRalpha-ABCA1 pathway and that
      lycopene and T0901317 exhibit synergistic effects.

PMID- 22137264
TI  - Coordinate expression and localization of iron and zinc transporters explain iron
      zinc interactions during uptake in Caco-2 cells: implications for iron uptake at
      the enterocyte.
AB  - Iron and zinc have diverse and important physiological functions. Yet, the
      mechanism of their absorption at the intestine remains controversial and is
      confounded by the fact that many studies have shown, to varying extents, that
      they inhibit the absorption of each other. We have studied the expression of iron
      and zinc transporters and storage proteins, and their regulation, in Caco-2
      cells, an established enterocyte model, under normal culture conditions and under
      conditions of iron and zinc depletion and supplementation using a combination of
      immunoblotting, confocal microscopy and reverse transcriptase polymerase chain
      reaction. We show that divalent metal transporter-1 (DMT-1) delocalizes from the
      plasma membrane upon iron or zinc depletion, but its apical abundance increases
      with zinc supplementation. This translocation of DMT-1 coincides with an increase
      in iron uptake upon zinc supplementation, as previously reported by us. FPN-1
      expression increases upon zinc supplementation and decreases with iron or zinc
      depletion, effluxing the excess sequestered iron and thus maintaining cellular
      iron homeostasis. Zinc influx transporters Zip-1 and Zip-14 and efflux
      transporters ZnT-1 and ZnT-4 are coordinately regulated under conditions of zinc
      supplementation and depletion to ensure cellular zinc homeostasis. We have
      previously reported that iron uptake can entail two transporters and that zinc
      noncompetitively inhibits iron uptake in Caco-2 cells. We now provide evidence
      that this inhibition is independent of DMT-1 and that Zip-14 may be a relevant
      iron transporter. These new observations provide experimental support to this two
      transporter model of iron uptake and give mechanistic insight to iron-zinc
      interactions during uptake at the enterocyte.

PMID- 22137262
TI  - Epigallocatechin gallate induces expression of heme oxygenase-1 in endothelial
      cells via p38 MAPK and Nrf-2 that suppresses proinflammatory actions of TNF
      alpha.
AB  - Epigallocatechin gallate (EGCG), the major polyphenol in green tea, acutely
      stimulates production of nitric oxide (NO) from vascular endothelium to reduce
      hypertension and improve endothelial dysfunction in spontaneously hypertensive
      rats. Herein, we explored additional mechanisms whereby EGCG may mediate
      beneficial cardiovascular actions. When compared with vehicle-treated controls,
      EGCG treatment (2.5 MUM, 8 h) of human aortic endothelial cells (HAEC) caused a
      ~three-fold increase in heme oxygenase-1 (HO-1) mRNA and protein with comparable
      increases in HO-1 activity. This was unaffected by pretreatment of cells with
      wortmannin, LY294002, PD98059 or L-NAME (PI 3-kinase, MEK and NO synthase
      inhibitors, respectively). Pretreatment of HAEC with SB203580 (p38 MAPK
      inhibitor) or siRNA knockdown of p38 MAPK completely blocked EGCG-stimulated
      induction of HO-1. EGCG treatment also inhibited tumor-necrosis-factor-alpha
      stimulated expression of vascular cell adhesion molecule (VCAM)-1 and decreased
      adhesion of monocytes to HAEC. siRNA knockdown of HO-1, p38 MAPK or Nrf-2 blocked
      these inhibitory actions of EGCG. In HAEC transiently transfected with a human HO
      1 promoter luciferase reporter (or an isolated Nrf-2 responsive region),
      luciferase activity increased in response to EGCG. This was inhibitable by
      SB203580 pretreatment. EGCG-stimulated expression of HO-1 and Nrf-2 was blocked
      by siRNA knockdown of Nrf-2 or p38 MAPK. Finally, liver from mice chronically
      treated with EGCG had increased HO-1 and decreased VCAM-1 expression. Thus, in
      vascular endothelium, EGCG requires p38 MAPK to increase expression of Nrf-2 that
      drives expression of HO-1, resulting in increased HO-1 activity. Increased HO-1
      expression may underlie anti-inflammatory actions of EGCG in vascular endothelium
      that may help mediate beneficial cardiovascular actions of green tea.

PMID- 22137265
TI  - L-Arginine stimulates the mTOR signaling pathway and protein synthesis in porcine
      trophectoderm cells.
AB  - Impairment of placental growth is a major factor contributing to intrauterine
      growth retardation (IUGR) in both human pregnancy and animal production. Results
      of recent studies indicate that administration of L-arginine (Arg) to gestating
      pigs or sheep with IUGR fetuses can enhance fetal growth. However, the underlying
      mechanisms are largely unknown. The present study tested the hypothesis that Arg
      stimulates the mammalian target of rapamycin (mTOR) signaling pathway and protein
      synthesis in porcine conceptus trophectoderm (pTr2) cells. The cells were
      cultured for 4 days in Arg-free Dulbecco's modified Eagle's Ham medium containing
      10, 50, 100, 200, 350 or 500 MUM Arg. Cell numbers, protein synthesis and
      degradation, as well as total and phosphorylated levels of mTOR, ribosomal
      protein S6 kinase 1 (p70S6K) and eukaryotic initiation factor 4E-binding protein
      1 (4EBP1), were determined. The pTr2 cells exhibited time (0-6 days)- and Arg
      concentration (10-350 MUM)-dependent increases in proliferation. Addition of 100
      and 350 MUM Arg to culture medium dose-dependently increased (a) protein
      synthesis and decreased protein degradation and (b) the abundance of total and
      phosphorylated mTOR, p70S6K and 4EBP1 proteins. Effects of 350 MUM Arg on
      intracellular protein turnover were only modestly affected when nitric oxide
      synthesis was inhibited. Collectively, these results indicate a novel and
      important role for Arg in promoting growth of porcine placental cells largely via
      a nitric-oxide-independent pathway. Additionally, these findings help to explain
      beneficial effects of Arg supplementation on improving survival and growth of
      embryos/fetuses in mammals.

PMID- 22137266
TI  - Docosahexaenoic acid attenuates macrophage-induced inflammation and improves
      insulin sensitivity in adipocytes-specific differential effects between LC n-3
      PUFA.
AB  - OBJECTIVE: Adipose tissue inflammation with immune cell recruitment plays a key
      role in obesity-induced insulin resistance (IR). Long-chain (LC) n-3
      polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) have anti-inflammatory potential; however, their
      individual effects on adipose IR are ill defined. We hypothesized that EPA and
      DHA may differentially affect macrophage-induced IR in adipocytes. METHODS:
      J774.2 macrophages pretreated with EPA or DHA (50 MUM for 5 days) were stimulated
      with lipopolysaccharide (LPS, 100 ng/ml for 30 min-48 h). Cytokine secretion
      profiles and activation status of macrophages were assessed by enzyme-linked
      immunosorbent assay and flow cytometry. Pretreated macrophages were seeded onto
      transwell inserts and placed over 3T3-L1 adipocytes for 24-72 h; effects on
      adipocyte-macrophage cytokine cross-talk and insulin-stimulated 3H-glucose
      transport into adipocytes were monitored. RESULTS: DHA had more potent anti
      inflammatory effects relative to EPA, with marked attenuation of LPS-induced
      nuclear factor (NF)kappaB activation and tumor necrosis factor (TNF)alpha
      secretion in macrophages. DHA specifically enhanced anti-inflammatory interleukin
      (IL)-10 secretion and reduced the expression of proinflammatory M1 (F4/80+/CD11+)
      macrophages. Co-culture of DHA-enriched macrophages with adipocytes attenuated IL
      6 and TNFalpha secretion while enhancing IL-10 secretion. Conditioned media (CM)
      from DHA-enriched macrophages attenuated adipocyte NFkappaB activation.
      Adipocytes co-cultured with DHA-enriched macrophages maintained insulin
      sensitivity with enhanced insulin-stimulated 3H-glucose transport, GLUT4
      translocation and preservation of insulin-receptor substrate-1 expression
      compared to co-culture with untreated macrophages. We confirmed that IL-10
      expressed by DHA-enriched macrophages attenuates the CM-induced proinflammatory
      IR phenotype in adipocytes. CONCLUSIONS: We demonstrate an attenuated
      proinflammatory phenotype of DHA-pretreated macrophages, which when co-cultured
      with adipocytes partially preserved insulin sensitivity.

PMID- 22137267
TI  - The acai flavonoid velutin is a potent anti-inflammatory agent: blockade of LPS
      mediated TNF-alpha and IL-6 production through inhibiting NF-kappaB activation
      and MAPK pathway.
AB  - Recent studies have shown that some flavonoids are modulators of proinflammatory
      cytokine production. In this study, velutin, a unique flavone isolated from the
      pulp of acai fruit (Euterpe oleracea Mart.), was examined for its effects in
      reducing lipopolysaccharide-induced proinflammatory cytokine tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-6 production in RAW 264.7 peripheral
      macrophages and mice peritoneal macrophages. Three other structurally similar and
      well-studied flavones, luteolin, apigenin and chrysoeriol, were included as
      controls and for comparative purposes. Velutin exhibited the greatest potency
      among all flavones in reducing TNF-alpha and IL-6 production. Velutin also showed
      the strongest inhibitory effect in nuclear factor (NF)-kappaB activation (as
      assessed by secreted alkaline phosphatase reporter assay) and exhibited the
      greatest effects in blocking the degradation of inhibitor of NF-kappaB as well as
      in inhibiting mitogen-activated protein kinase p38 and JNK phosphorylation; all
      of these are important signaling pathways involved in production of TNF-alpha and
      IL-6. The present study led to the discovery of a strong anti-inflammatory
      flavone, velutin. This compound effectively inhibited the expression of
      proinflammatory cytokines TNF-alpha and IL-6 in low micromole levels by
      inhibiting NF-kappaB activation and p38 and JNK phosphorylation.

PMID- 22137268
TI  - Marginal selenium deficiency down-regulates inflammation-related genes in splenic
      leukocytes of the mouse.
AB  - Moderate selenium deficiency may lead to an impaired capacity to cope with health
      challenges. Functional effects of suboptimal selenium intake are not fully known,
      and biomarkers for an insufficient selenium supply are inadequate. We therefore
      fed mice diets of moderately deficient or adequate selenium intake for 6 weeks.
      Changes in global gene expression were monitored by microarray analysis in
      splenic leukocytes. Genes for four selenoproteins, Sepw1, Gpx1, Selh and Sep15,
      were the most significantly down-regulated in moderate selenium deficiency, and
      this was confirmed by quantitative polymerase chain reaction (qPCR).
      Classification of significantly affected genes revealed that processes related to
      inflammation, heme biosynthesis, DNA replication and transcription, cell cycle
      and transport were affected by selenium restriction. Down-regulation by moderate
      selenium deficiency of specific genes involved in inflammation and heme
      biosynthesis was confirmed by qPCR. Myeloperoxidase and lysozyme activities were
      decreased in selenium-restricted leukocytes, providing evidence for functional
      consequences. Genes for 31 nuclear factor (NF)-kappaB targets were down-regulated
      in moderate selenium deficiency, indicating an impaired NF-kappaB signaling.
      Together, the observed changes point to a disturbance in inflammatory response.
      The selenoproteins found here to be sensitive to selenium intake in murine
      leukocytes might also be useful as biomarkers for a moderate selenium deficiency
      in humans.

PMID- 22137269
TI  - Treatment with low-dose resveratrol reverses cardiac impairment in obese prone
      but not in obese resistant rats.
AB  - We hypothesized that a low-dose resveratrol will reverse cardiovascular
      abnormalities in rats fed a high-fat (HF) diet. Obese prone (OP) and obese
      resistant (OR) rats were fed an HF diet for 17 weeks; Sprague-Dawley rats fed
      laboratory chow served as control animals. During the last 5 weeks of study,
      treatment group received resveratrol daily by oral gavage at a dosage of 2.5
      mg/kg body weight. Assessments included echocardiography, blood pressure,
      adiposity, glycemia, insulinemia, lipidemia, and inflammatory and oxidative
      stress markers. Body weight and adiposity were significantly higher in OP rats
      when compared to OR rats. Echocardiographic measurements showed prolonged
      isovolumic relaxation time in HF-fed OP and OR rats. Treatment with resveratrol
      significantly improved diastolic function in OP but not in OR rats without
      affecting adiposity. OP and OR rats had increased blood pressure which remained
      unchanged with treatment. OP rats had elevated fasting serum glucose and insulin,
      whereas OR rats had increased serum glucose and normal insulin concentrations.
      Resveratrol treatment significantly reduced serum glucose while increasing serum
      insulin in both OP and OR rats. Inflammatory and oxidative stress markers, serum
      triglycerides and low-density lipoprotein were higher in OP rats, which were
      significantly reduced with treatment. In conclusion, HF induced cardiac
      dysfunction in both OP and OR rats. Treatment reversed abnormalities in diastolic
      heart function associated with HF feeding in OP rats, but not in OR rats. The
      beneficial effects of resveratrol may be mediated through regression of
      hyperglycemia, oxidative stress and inflammation.

PMID- 22137270
TI  - First report of mefA and msrA/msrB multidrug efflux pumps associated with blaTEM
      1 beta-lactamase in Enterococcus faecalis.
AB  - OBJECTIVES: Enterococcus faecalis is thought to possess a great deal of intrinsic
      resistance to several antimicrobial agents. In this study we identified
      ampicillin- and erythromycin-resistant clinical isolates of E. faecalis and
      sought to identify the resistance mechanisms among these isolates. METHODS:
      Twelve isolates of E. faecalis were collected from 12 different patients.
      Identification of the isolates and their susceptibility patterns were determined
      using the Phoenix automated phenotypic identification criteria. PCR amplification
      and sequencing were used to detect beta-lactamase production. Colony blotting was
      performed in order to screen for multidrug efflux pump production. Extraction and
      N-terminal sequencing of the multidrug efflux pumps was carried out. RESULTS: The
      E. faecalis isolates showed high resistance to erythromycin and ampicillin, with
      minimum inhibitory concentrations of >16 MUg/ml. PCR amplification and sequencing
      showed that isolates produced TEM-1 beta-lactamase. Colony blotting showed that
      these isolates harbored multidrug efflux pump genes. Multidrug efflux pump
      extraction, purification, and sequencing showed the distribution of mefA and
      msrA/msrB efflux pumps. CONCLUSION: Two resistance mechanisms among E. faecalis
      are described - the production of TEM beta-lactamase and mefA and msrA/msrB
      efflux pumps. These results are of great interest because this is the first
      report of the co-existence of these resistance mechanisms among E. faecalis
      strains.

PMID- 22137271
TI  - The role of combination antifungal therapy in the treatment of invasive
      aspergillosis: a systematic review.
AB  - BACKGROUND: Because treatment outcomes of invasive aspergillosis (IA) remain
      suboptimal, clinicians have resorted to the use of combination antifungal
      therapy. We therefore sought to systematically review the evidence that addresses
      the role of combination antifungal therapy in the treatment of invasive
      aspergillosis. METHODS: We retrieved the literature from MEDLINE, EMBASE, Web of
      Science, Cochrane Controlled Trials Register, and Scopus from inception up to
      March 2011 for cohort and randomized controlled trial (RCT) studies that assessed
      the efficacy of combination antifungal therapy for IA and reported on clinical
      outcomes. RESULTS: Eight studies (one RCT and seven cohort studies) that enrolled
      a total of 1071 patients met our inclusion criteria. Six cohort studies examined
      the role of combination therapy for the primary treatment of IA and two for
      salvage therapy. Various antifungal combinations were used, mainly azoles with
      either an echinocandin or a polyene. Of the seven cohort studies, four reported
      adjusted effect estimates, one of which showed a better outcome with combination
      antifungal therapy and one a trend towards a better outcome, while the remaining
      two revealed that there was no added advantage of combination antifungal therapy
      over monotherapy or a better response with monotherapy, respectively. The
      randomized controlled trial revealed that the use of combination therapy was
      associated with a better outcome. CONCLUSION: Cumulative evidence supporting the
      use of combination antifungal therapy in IA is conflicting and of moderate
      strength. Well-designed RCTs are required to adequately address the issue of the
      usefulness of this approach.

PMID- 22137273
TI  - Catalytic production of 1,2-propanediol from glycerol in bio-ethanol solvent.
AB  - Production of 1,2-propanediol (1,2-PDO) from glycerol hydrogenolysis was carried
      out in bio-ethanol solvent over small amount of Rh-promoted Cu/solid-base
      catalysts prepared via layered double hydroxide precursors. It was found that
      glycerol hydrogenolysis proceeded easily on Rh-Cu/solid-base catalysts than
      separated Rh and Cu/solid-base. The conversion of glycerol and selectivity to 1,2
      PDO over Rh(0.02)Cu(0.4)/Mg(5.6)Al(1.98)O(8.57) reached 91.0% and 98.7%,
      respectively, at 2.0 MPa H(2), 180  degrees C. And this catalyst was stable in
      five consecutive hydrogenolysis tests in ethanol.

PMID- 22137272
TI  - Immobilization of laccase on magnetic bimodal mesoporous carbon and the
      application in the removal of phenolic compounds.
AB  - A novel magnetically separable laccase immobilized system was constructed by
      adsorbing laccase into bimodal carbon-based mesoporous magnetic composites
      (CMMC). A large adsorption capacity (491.7 mg g(-1)), excellent activity recovery
      (91.0%) and broader pH and temperature profiles than free laccase have been
      exhibited by the immobilized laccase. Thermal stability was enhanced to a great
      extent and operational stability was increased to a certain extent. The shift of
      kinetic parameters indicated affinity change between enzyme and substrate.
      Application of the immobilized system in phenol and p-chlorophenol removal was
      investigated in a batch system. Adsorption effects of the support were
      responsible for the quick removal rate in the first hour, and up to 78% and 84%
      of phenol and p-chlorophenol were removed in the end of the reaction,
      respectively, indicating that the magnetic bimodal mesoporous carbon is a
      promising carrier for both immobilization of laccase and further application in
      phenol removal.

PMID- 22137274
TI  - Endocrine disruptive estrogens role in electron transfer: bio-electrochemical
      remediation with microbial mediated electrogenesis.
AB  - Bioremediation of selected endocrine disrupting compounds (EDCs)/estrogens viz.
      estriol (E3) and ethynylestradiol (EE2) was evaluated in bio-electrochemical
      treatment (BET) system with simultaneous power generation. Estrogens
      supplementation along with wastewater documented enhanced electrogenic activity
      indicating their function in electron transfer between biocatalyst and anode as
      electron shuttler. EE2 addition showed more positive impact on the electrogenic
      activity compared to E3 supplementation. Higher estrogen concentration showed
      inhibitory effect on the BET performance. Poising potential during start up phase
      showed a marginal influence on the power output. The electrons generated during
      substrate degradation might have been utilized for the EDCs break down. Fuel cell
      behavior and anodic oxidation potential supported the observed electrogenic
      activity with the function of estrogens removal. Voltammetric profiles,
      dehydrogenase and phosphatase enzyme activities were also found to be in
      agreement with the power generation, electron discharge and estrogens removal.

PMID- 22137275
TI  - The role of the Epstein-Barr virus receptor CD21 in multiple sclerosis.
AB  - Multiple Sclerosis (MS) is characterised by a chronic inflammation and
      demyelination of brain and spinal cord with a yet unknown aetiology. Based on
      multiple epidemiological and immunological studies, which suggest a role of
      Epstein-Barr virus (EBV) infection in the pathogenesis of MS, we investigated
      CD21 (CR2, complement receptor type 2), which serves as the EBV receptor. Serum
      concentrations of soluble CD21 receptor (sCD21) were determined in MS patients
      and controls. In accordance with findings in other autoimmune disorders decreased
      sCD21 levels were found in MS patients. On beta-IFN treatment serum sCD21
      concentrations further decreased. To explore the role of the CD21 gene for MS
      susceptibility and the altered CD21 levels in MS patients we performed exon
      sequencing of the CD21 gene. While we identified new single nucleotide
      polymorphism (SNP) and confirmed previously reported SNPs, none of the SNPs was
      associated with MS. Our findings demonstrate that sCD21 expression is altered in
      MS patients similar to other autoimmune diseases although no evidence was found
      for a specific role of the CD21 gene in MS.

PMID- 22137276
TI  - [Acute chest syndrome of adults suffering from sickle cell disease].
AB  - Sickle cell disease is a common but often poorly understood by chest physicians.
      The acute chest syndrome represents its main respiratory complication. STATE OF
      ART: Sickle cell disease is an autosomal recessive disorder inducing, in certain
      circumstances, sickling of red cells. Natives from western or central Africa and
      from the Caribbean islands are mainly affected. Acute chest syndrome is defined
      by the association of chest pain or fever and recent radiographic infiltrates, in
      patients suffering from sickle cell disease. Determination of etiology,
      infection, fat embolism or hypoventilation, is difficult, as a self-perpetuating
      vicious circle is ongoing. Support, largely undervalued, is based on etiological
      treatment and measures to avoid worsening linked to complications, especially
      microcirculatory disease. CONCLUSIONS: Acute chest syndrome is a severe
      respiratory complication of sickle cell disease. Therapeutic measures are simple
      but undervalued.

PMID- 22137277
TI  - [Renal failure in sarcoidosis].
AB  - Renal sarcoidosis is rare and may lead to renal failure in less than 3% of
      patients. It may occur as a consequence of calcium metabolism disorders or
      granulomatous interstitial nephritis. In this retrospective study, we present
      five patients with renal failure secondary to sarcoidosis diagnosed in our centre
      on one period of nine years. Patients were three males and two females with a
      mean age at the time of the diagnosis of 31,6 years. Pulmonary involvement was
      present in three cases. Renal biopsy revealed granulomatous interstitial
      nephritis lesions in all patients. Extra-membranous glomerulonephritis was
      present in one case. In another case, moderate interstitial fibrosis was
      observed. Corticosteroid therapy using prednisolone 1mg/kg per day was used in
      all patients. Three patients had methylprednisolone pulse before oral
      corticosteroid therapy. One patient required several sessions of haemodialysis.
      All patients were followed up for a mean period of 52,6 months (ranged from 13 to
      84 months). All patients improved their renal function with normalization of
      creatininemia in two of them. Renal involvement in sarcoidosis is probably
      underestimated. Corticosteroids therapy is efficient and must be introduced early
      to prevent progression to chronic renal failure.

PMID- 22137278
TI  - [Knowledge, attitudes and behaviors of hospital staff members towards smoking and
      anti-smoking regulations: results of a survey in F.-Hached University Teaching
      Hospital of Sousse (Tunisia)].
AB  - BACKGROUND: Promoting a smoke-free hospital is a priority component for tobacco
      control strategies. The aim of our investigation was to study the attitudes and
      behaviors of the hospital staff of the F.-Hached UH of Sousse towards smoking,
      and to assess their knowledge about the harms of passive smoking and about
      tobacco regulations in the hospital. METHODS: We conducted a descriptive cross
      sectional study using an anonymous self-administered questionnaire. In January
      February 2008, the questionnaire was submitted to hospital staff members selected
      at random from the care units at F.-Hached UH of Sousse, Tunisia. RESULTS: The
      response rate was 92.8% (452 participants). The average age of the population was
      39.7+/-19 years; all professional categories were represented. The prevalence of
      active smoking among the staff interviewed was 19% (89.5% males). About 75% of
      the smokers stated they smoked on the work site and 8% in the presence of
      patients. The majority of the smokers wished to stop smoking. Discomfort from
      exposure to tobacco smoke was reported by 83.4% of respondents. The large
      majority of staff respondents (95%) knew that tobacco smoke is dangerous and 80%
      were aware of the existence of a law that prohibits smoking in the hospital.
      CONCLUSION: The prevalence of smoking remains high among male hospital workers.
      In our hospital, the majority of the care staff favored promotion of a tobacco
      free hospital. The success of this project will depend on education, implicating
      the entire hospital staff in the anti-smoking battle. Smoking staff members
      should be supported in their attempts to stop smoking.

PMID- 22137279
TI  - [Isoniazid-induced myopathy].
AB  - Drug-induced muscle disorders are now well known and vary from a simple isolated
      increase in muscle enzymes to severe drug-induced myopathy. The list of drugs
      inducing myopathy is very long and continues to grow. The onset of muscle
      disorders under isoniazid often falls within a drug-induced neuropathy or a drug
      induced lupus. However, the occurrence of isolated isoniazid-induced drug
      myopathy without neuropathy is an extremely rare condition especially with non
      toxic doses. The authors report the case of a 28-year-old man, without a previous
      medical history, hospitalized for pulmonary tuberculosis. After initiating
      tuberculosis treatment for five days, he presented muscle pain, fasciculation and
      weakness initially involving the lower left limb that quickly propagated to all
      four limbs. The physical examination noted a left ankle flush, a swollen left
      calf and fasciculation of both calves while the neurological examination was
      normal. The CPK was normal. Electromyography confirmed the myopathy without
      neuropathic findings. Isoniazid withdrawal was marked by the rapid disappearance
      of the symptoms. The reintroduction of a half-dose of isoniazid only induced a
      few transitional muscular fasciculations. The onset of the symptoms under
      tuberculosis treatment, the absence of later muscle disorders, the absence of any
      other cause of myopathy and the total disappearance of the symptoms after
      isoniazid withdrawal confirmed the diagnosis of isoniazid-induced myopathy.

PMID- 22137280
TI  - [A case of costal haemangioma].
AB  - Costal primary tumors are rare and dominated by malignant tumors. Haemangioma of
      the bone represents only 1% of bone tumors. Costal localization accounts only for
      1% of the cases and only about fifty cases have been reported in the literature.
      AIM: The authors aim to describe a rare costal tumor, its histological features
      and the main differential diagnoses. OBSERVATION: The authors describe the case
      of a 46-year-old woman who presented with chest pain. Radiological findings did
      not permit a malignant tumor to be ruled out and the treatment consisted of a
      resection of the posterior arch of the rib. Microscopic examination concluded
      that the patient had a costal haemangioma and the patient didn't present any
      recurrence after a six-year follow-up. CONCLUSION: The costal haemangioma is a
      very rare tumor with a debated etiology. Some radiological features are specific
      such as the "soap bubble" or "honeycomb" aspect. However, the basis for diagnosis
      remains microscopic examination. These tumors have a good prognosis and no cases
      of recurrence have been reported following complete resection.

PMID- 22137281
TI  - [Eosinophilic pleural effusion related to taking valproic acid].
AB  - Eosinophilic pleural effusions have multiple aetiologies. We report on the case
      of a 40-year-old man who experienced an eosinophilic pleural effusion with blood
      hypereosinophilia that occurred nine weeks after a treatment with valproic acid
      was introduced. Usual aetiologies of eosinophilic pleural effusion were excluded.
      Once valproic acid was discontinued, both pleural effusion and blood eosinophilia
      decreased rapidly. The persistence of a residual pleural effusion required the
      introduction of oral corticosteroids, which resulted in the effusion disappearing
      completely and rapidly. Valproic acid is a rare cause of eosinophilic pleural
      effusion. The effusion usually regresses when treatment is discontinued but short
      term oral corticotherapy may be necessary in order to heal the patient.

PMID- 22137282
TI  - [Acute interstitial lung disease revealing antisynthetase syndrome].
AB  - INTRODUCTION: The antisynthetase syndrome is characterized by the presence of
      myositis, interstitial lung disease, arthritis, Raynaud's phenomenon, mechanics
      hands and anti-Jo1 antibody (histidyl tRNA synthetase). The prognosis of this
      syndrome is closely related to the severity of lung disease. Myositis can occur
      several years after lung disease and some patients with interstitial lung disease
      associated with anti-Jo1 antibodies will not suffer from muscle disease. CASE
      REPORT: We report the case of a 69-year-old man admitted to the medical intensive
      care unit for acute respiratory insufficiency related to rapidly progressive
      interstitial lung disease. Antisynthetase syndrome was diagnosed the presence of
      wrists' arthritis, 'mechanic's hands and anti-Jo1 antibodies. Despite the
      dramatic efficacy of corticosteroid therapy on ventilation parameters, the
      patient died from a Pseudomonas Aeruginosa nosocomial ventilator-acquired
      pneumonia. CONCLUSION: Our case emphasizes the importance to search for anti-Jo1
      antibodies in the presence of interstitial lung disease. During the course of
      antisynthetase syndrome, the occurrence of interstitial lung disease is almost
      always constant and is correlated with poor prognosis.

PMID- 22137283
TI  - [Pediatric Ewing sarcoma of the rib: role of neoadjuvant chemotherapy in tumoral
      shrinking and sterilization. A case report].
AB  - Ewing sarcoma is a rare tumor, which represents, nevertheless, the most common
      primary chest wall tumor in children. The management and prognosis of these
      tumors have markedly improved with the use of multimodal therapy including
      adjuvant chemotherapy, surgery and/or irradiation. A good response to
      chemotherapy often avoids the need for extensive local treatment without
      sacrificing local control or long-term survival. Here, we report a new case of a
      bulky rib Ewing sarcoma, well managed by neoadjuvant chemotherapy resulting in
      significantly tumor shrinking that allowed complete resection. At the
      histological examination of the specimen, there was only inflammatory and
      fibrosis tissues without viable tumoral tissue.

PMID- 22137284
TI  - [Atypical metastatic site of lung adenocarcinoma].
AB  - The case concerns a 40 years old smoker male, treated for an adenocarcinoma of
      the left upper lobe, metastatic in muscle extended to the right femur cortex. The
      patient had first a surgical excision of the mass of the thigh, an intramedullary
      femoral nailing, and six courses of chemotherapy (cisplatin-vinorelbine) with
      concurrent thoracic radiotherapy. This treatment led to disease stability. One
      year later, hematuria revealed a bladder tumor. Cystoscopy with biopsy concluded
      to an adenocarcinoma pulmonary origin. The PET-scanner showed an uptake of the
      bladder mass, a hypermetabolic right adrenal gland and subcutaneous left shoulder
      nodule. The patient had a partial cystectomy associated with enterocystoplasty
      and left ureteral reimplantation, plus excision of the subcutaneous nodule
      located in the left shoulder and a right adrenalectomy during the same time. All
      of the sites were metastasis from adenocarcinoma of pulmonary origin. A salvage
      chemotherapy was initiated. In the vast majority of cases, bladder metastasis as
      primary bladder tumours is revealed by hematuria, cystitis or sometimes vague
      pelvic pain. Our case is a very unusual bladder metastatic site from lung cancer.
      We will discuss the different procedures and the therapeutic strategies on the
      basis of the published data.

PMID- 22137285
TI  - [Bilio-bronchial fistula due to hydatic disease: case report and review of the
      literature].
AB  - Bilio-bronchial fistula due to hydatid disease is a rare but severe condition.
      Three levels, abdominal, diaphragmatic and thoracic, may be involved, with high
      perioperative mortality. We report a case of bilio-bronchial fistula successfully
      managed by thoracotomy. Thoracotomy is the best approach for surgical treatment
      at all three levels.

PMID- 22137286
TI  - [Death following administration of pristinamycine and colchicine].

PMID- 22137287
TI  - [An unexplained fall in a 65-year-old patient].

PMID- 22137288
TI  - [Nutritional management in amyotrophic lateral sclerosis: A medical and ethical
      stake].
AB  - Malnutrition and dehydration are common and result from swallowing disorders
      secondary to degeneration of brainstem motor neurons. Recent knowledge argues in
      favor of the associated primary metabolism abnormalities. Though muscle atrophy,
      a paradoxical hypermetabolism at rest has often been observed. Hyperlipidemia and
      glucose intolerance are more frequent than in general population. The
      heterogeneity of the nutritional assessment of patients in published series is
      due, partially at least, to the use of disparate criteria and evaluating
      procedures. Weight lost is an independent negative survival prognostic factor.
      Overweight may be beneficial for the survival of ALS patients. A specific
      nutritional management for ALS is an essential point in the multidisciplinary
      support. The criteria leading to artificial nutrition indication are medical,
      mainly based on percentage of weight loss, but also psychological and ethical.

PMID- 22137289
TI  - [Potential severity of self-poisoning with trimebutine].

PMID- 22137290
TI  - [Pneumatosis cystoides intestinalis in the colon].

PMID- 22137291
TI  - Characteristic analysis on temporal evolution of floc size and structure in low
      shear flow.
AB  - A series of flocculation tests were performed to investigate the effect of low
      shear rates (G = 3-16 s(-1)) on flocculation of kaolin suspension by polyaluminum
      chloride (PACl), with the goal of understanding floc growth mechanisms. Results
      were reported in terms of floc average size (d(p)) and boundary fractal dimension
      (D(pf)), derived from a non-intrusive optical sampling and digital image analysis
      technique. As expected, the rate of floc aggregation increased with increasing G,
      resulting in faster changes in aggregate size and structure in the initial stage
      of flocculation. Nevertheless, steady state was attained faster for D(pf) than
      for d(p) at the same shear rates, possibly due to the self-similarity of fractal
      aggregates. An interesting finding was that at G = 3 s(-1), an obvious plateau
      was observed for the average-size evolution at steady state; for shear rates of 6
      and 7 s(-1), the flocs exhibited some decrease after reaching the peak of size,
      mainly as a result of floc settling at steady state; and for G = 11-16 s(-1), a
      decrease in floc size was possibly attributed to the irreversibility of PACl-floc
      breakage. The process of floc growth was described using a fractal growth model,
      which defined flocculation as the result of the combined processes of aggregation
      and restructuring. The conceptual model could effectively characterize temporal
      changes in floc size and structure, and found that fragmentation followed by
      reformation seemed to be more effective in forming larger and more compact
      aggregates than the restructuring process due to erosion and reformation, which
      may provide useful insights for the design of flocculation reactors.

PMID- 22137292
TI  - Effects of ozone and ozone/peroxide on trace organic contaminants and NDMA in
      drinking water and water reuse applications.
AB  - An ozone and ozone/peroxide oxidation process was evaluated at pilot scale for
      trace organic contaminant (TOrC) mitigation and NDMA formation in both drinking
      water and water reuse applications. A reverse osmosis (RO) pilot was also
      evaluated as part of the water reuse treatment train. Ozone/peroxide showed lower
      electrical energy per order of removal (EEO) values for TOrCs in surface water
      treatment, but the addition of hydrogen peroxide increased EEO values during
      wastewater treatment. TOrC oxidation was correlated to changes in UV(254)
      absorbance and fluorescence offering a surrogate model for predicting contaminant
      removal. A decrease in N-nitrosodimethylamine (NDMA) formation potential (after
      chloramination) was observed after treatment with ozone and ozone/peroxide.
      However, during spiking experiments with surface water, ozone/peroxide achieved
      limited destruction of NDMA, while in wastewaters net direct formation of NDMA of
      6-33 ng/L was observed after either ozone or ozone/peroxide treatment. Once
      formed during ozonation, NDMA passed through the subsequent RO membranes, which
      highlights the significance of the potential for direct NDMA formation during
      oxidation in reuse applications.

PMID- 22137293
TI  - Toxic cyanobacterial breakthrough and accumulation in a drinking water plant: a
      monitoring and treatment challenge.
AB  - The detection of cyanobacteria and their associated toxins has intensified in
      recent years in both drinking water sources and the raw water of drinking water
      treatment plants (DWTPs). The objectives of this study were to: 1) estimate the
      breakthrough and accumulation of toxic cyanobacteria in water, scums and sludge
      inside a DWTP, and 2) to determine whether chlorination can be an efficient
      barrier to the prevention of cyanotoxin breakthrough in drinking water. In a full
      scale DWTP, the fate of cyanobacteria and their associated toxins was studied
      after the addition of coagulant and powdered activated carbon, post
      clarification, within the clarifier sludge bed, after filtration and final
      chlorination. Elevated cyanobacterial cell numbers (4.7 * 10(6)cells/mL) and
      total microcystins concentrations (up to 10 mg/L) accumulated in the clarifiers
      of the treatment plant. Breakthrough of cells and toxins in filtered water was
      observed. Also, a total microcystins concentration of 2.47 MUg/L was measured in
      chlorinated drinking water. Cyanobacterial cells and toxins from environmental
      bloom samples were more resistant to chlorination than results obtained using
      laboratory cultured cells and dissolved standard toxins.

PMID- 22137294
TI  - The complement component C5a receptor mediates pain and inflammation in a
      postsurgical pain model.
AB  - The complement system is an important part of innate immunity. Complement
      activation generates a set of effector molecules with diverse biological
      functions. C5a is a crucial terminal component of the complement cascade. Several
      reports suggest that C5a can support nociceptive sensitization and inflammation
      in various models, including models of incisional pain. However, information
      concerning the differential effects of C5a on specific modalities of nociception,
      the role of C5a in supporting neutrophil infiltration, secondary nociceptive
      mediator generation, and the location of the relevant populations of C5a
      receptors supporting incisional sensitization are needed. In these studies we
      utilized C5a receptor-null mice (C5aR(-/-)) and matched controls to study
      nociceptive changes after hind paw incision. Heat hyperalgesia and mechanical
      allodynia were measured for 4 days after incision. We also followed hind paw
      edema, wound area neutrophil infiltration using the myeloperoxidase assay, and
      interleukin-1beta and nerve growth factor levels using both enzyme-linked
      immunosorbent assay and immunohistochemical techniques. The main findings were:
      (1) Heat vs mechanical nociceptive sensitization after incision were
      differentially reduced in C5aR(-/-) mice, with thermal sensitization affected
      throughout the postincisional period but mechanical sensitization affected only
      at later time points; (2) Edema developed after incision in wild-type mice but
      only slightly and transiently in C5aR(-/-) mice, and (3) Deletion of C5aR blocked
      interleukin-1beta and nerve growth factor production near the wound site. These
      findings demonstrate that the complement system component C5a is a novel
      biomarker and mediator associated with postsurgical nociceptive processing. C5aR
      may provide a novel target for the control of pain and inflammation after
      surgery.

PMID- 22137296
TI  - Multisystem complications following endodontic therapy.

PMID- 22137295
TI  - Purinergic receptor P2Y1 regulates polymodal C-fiber thermal thresholds and
      sensory neuron phenotypic switching during peripheral inflammation.
AB  - We have recently found that, following complete Freund's adjuvant (CFA)-induced
      inflammation, cutaneous polymodal nociceptors (CPM) lacking the transient
      receptor potential vanilloid 1 (TRPV1) are sensitized to heat stimuli. In order
      to determine possible mechanisms playing a role in this change, we examined gene
      expression in the L2/L3 sensory ganglia following CFA injection into the hairy
      hind paw skin and found that G-protein-coupled purinoreceptor P2Y1 expression was
      increased. This receptor is of particular interest, as most CPMs innervating
      mouse hairy skin bind isolectin B4, which co-localizes with P2Y1. Additionally,
      our recent findings have shown that cutaneous CPMs in P2Y1-/- mice displayed
      significantly reduced thermal sensitivity. Together, these findings suggested a
      possible role for P2Y1 in inflammation-induced heat sensitization in these
      fibers. To test this hypothesis, we utilized our in vivo small interfering RNA
      technique to knock down the inflammation-induced increase in P2Y1 expression and
      then examined the functional effects using ex vivo recording. We found that the
      normal reduction of heat thresholds in CPM fibers induced by CFA was completely
      blocked by inhibition of P2Y1. Surprisingly, inhibition of P2Y1 during
      inflammation also significantly increased the number of CPM neurons expressing
      TRPV1 without a change in the total number of TRPV1-positive cells in the L2 and
      L3 dorsal root ganglia. These results show that the inflammation-induced enhanced
      expression of P2Y1 is required for normal heat sensitization of cutaneous CPM
      fibers. They also suggest that P2Y1 plays a role in the maintenance of phenotype
      in cutaneous afferent fibers containing TRPV1.

PMID- 22137297
TI  - Tuberculosis in Texas 2011--victories and challenges.

PMID- 22137299
TI  - Invited commentary.

PMID- 22137300
TI  - Invited commentary.

PMID- 22137301
TI  - Long-term single institution comparison of endovascular aneurysm repair and open
      aortic aneurysm repair.
AB  - INTRODUCTION: Since the development of endovascular aneurysm repair (EVAR), there
      remains concerns regarding its durability, need for secondary procedures, and
      associated long-term morbidity. We compared these two approaches to evaluate
      secondary interventions and their respective long-term durability. METHODS: All
      patients who had undergone endovascular and open abdominal aortic aneurysm (AAA)
      repair were identified from a prospectively maintained registry. Health system
      charts, medical communication, and national death indexes were reviewed.
      Secondary interventions were classified as vascular (aortic graft or remote) and
      nonvascular (incisional or gastrointestinal). RESULTS: Between July 1985 and
      September 2009, 1908 patients underwent 1986 AAA repair procedures (EVAR = 1066;
      open = 920). Patients were followed up to 290 months (mean 27.6 +/- 35.9) and
      identified with 427 surgical encounters (EVAR 233% to 21.9%; open 194% to 21.1%).
      Most encounters (338% to 74.6%) were related to vascular disease: 178 (EVAR =
      131; open = 47) related to the aortic graft; 160 (EVAR = 93; open = 67) were
      related to nonaortic vascular disease. The remaining 89 surgical encounters
      included incisional hernias, small bowel obstruction, intra-abdominal abscesses,
      and wound dehiscence requiring operation. Of these 89 encounters (EVAR = 9; open
      = 80), 44 patients required surgical intervention and 36 required hospitalization
      without surgical procedure. Over the period of 100 months, the all-cause
      mortality rate was 25.2% after EVAR and 39.1% after open repair. One-year
      survival was 88.0% (SE 0.01) and 85.0% (SE 0.01), while 5-year survival was 58.0%
      (SE 0.02) and 53.0% (SE 0.02) for EVAR and open repair, respectively (log-rank P
      value < .0164). Seven-year survival was 46% (SE 0.03) for EVAR and 36% (SE 0.03)
      for open AAA repair. CONCLUSION: EVAR requires more late secondary vascular
      interventions than open AAA repair, but patients who undergo open repair have
      more nonvascular long-term morbidity. Long-term survival is better after EVAR
      compared to open repair in this selected patient group.

PMID- 22137303
TI  - Invited commentary.

PMID- 22137304
TI  - Invited commentary.

PMID- 22137306
TI  - How informed need be informed consent?
AB  - Dr C. Lever is a pioneer in endovascular infrarenal aneurysmectomy, with some of
      the best results published in the literature. He attempted an endovascular stent
      in an octogenarian that required an acute open repair. The procedure was touch
      and-go and the postoperative course a train wreck, with multiple organ
      dysfunction syndrome. After steadily deteriorating, the patient died. The son has
      filed a lawsuit claiming Dr Lever did not specify that a standard procedure might
      need to be done as an emergency. Dr Lever usually indicates an open procedure
      might be necessary, but the resident did not include whether or not Dr Lever did
      so in the informed consent note. Regarding technical details in the informed
      consent note: A. Always include operative details that will increase the risk, no
      matter how rare. B. Operative details are not necessary. C. Complications are the
      only necessary important components of informed consent documentation. D. As long
      as you postoperatively document what happened in the OR, you are legally and
      ethically all right. E. Every factor that could influence the patient's decision
      must be mentioned and then adequately documented.

PMID- 22137309
TI  - Regarding "Outcomes of carotid artery stenting versus historical surgical
      controls for radiation-induced carotid stenosis".

PMID- 22137311
TI  - Regarding "Evaluation of the Endurant stent graft under instructions for use vs
      off label conditions for endovascular aortic aneurysm repair".

PMID- 22137312
TI  - Carotid artery stenting may be contraindicated in female patients with
      symptomatic carotid artery stenosis.

PMID- 22137313
TI  - Regarding "Repairing immediate proximal endoleaks during abdominal aortic
      aneurysm repair".

PMID- 22137316
TI  - Clinical profile and outcome of patients of acute myeloid leukemia with high
      hyperdiploidy.

PMID- 22137318
TI  - Update on developments in the diagnosis and prognostic evaluation of patients
      with myelodysplastic syndromes (MDS): consensus statements and report from an
      expert workshop.
AB  - Several new treatments for myelodysplastic syndromes (MDS) have recently become
      available, or are in development. Patients who could benefit from active
      treatment must be effectively identified and followed up. Therefore, guidelines
      for the diagnosis and prognostic evaluation of MDS need to be kept up to date
      with technological and scientific advances. An expert workshop was convened to
      review currently available and emerging diagnostic technologies and developments
      in prognostic classification systems, to ensure appropriate management of
      individual patients. The panel also provided suggestions to ensure adherence to
      guidelines and highlighted the mandatory requirement for cytogenetic evaluation
      in patients with MDS.

PMID- 22137317
TI  - Synergistic activity of rapamycin and dexamethasone in vitro and in vivo in acute
      lymphoblastic leukemia via cell-cycle arrest and apoptosis.
AB  - Activation of the mTOR pathway subsequent to phosphatase and tensin homolog
      (PTEN) mutation may be associated with glucocorticoid (GC) resistance in acute
      lymphoblastic leukemia (ALL). The combination activity of rapamycin and
      dexamethasone in cell lines and xenograft models of ALL was determined. Compared
      with either drug alone, dexamethasone+rapamycin showed significantly greater
      apoptosis and cell cycle arrest in some cell lines, and was more frequently seen
      in T-lineage cell lines with PTEN mutation. The combination significantly
      extended the event-free survival of mice carrying PTEN mutated xenografts. Our
      data suggest that PI3K/mTOR pathway inhibitors could benefit patients with PTEN
      mutated T-ALL.

PMID- 22137319
TI  - Combustion and inorganic bromine emission of waste printed circuit boards in a
      high temperature furnace.
AB  - High temperature combustion experiments of waste printed circuit boards (PCBs)
      were conducted using a lab-scale system featuring a continuously-fed drop tube
      furnace. Combustion efficiency and the occurrence of inorganic bromine (HBr and
      Br(2)) were systematically studied by monitoring the main combustion products
      continuously. The influence of furnace temperature (T) was studied from 800 to
      1400 degrees C, the excess air factor (EAF) was varied from 1.2 to 1.9 and the
      residence time in the high temperature zone (RT(HT)) was set at 0.25, 0.5, or
      0.75 s. Combustion efficiency depends on temperature, EAF and RT(HT); temperature
      has the most significant effect. Conversion of organic bromine from flame
      retardants into HBr and Br(2) depends on temperature and EAF. Temperature has
      crucial influence over the ratio of HBr to Br(2), whereas oxygen partial pressure
      plays a minor role. The two forms of inorganic bromine seem substantially to
      reach thermodynamic equilibrium within 0.25s. High temperature is required to
      improve the combustion performance: at 1200 degrees C or higher, an EAF of 1.3 or
      more, and a RT(HT) exceeding 0.75 s, combustion is quite complete, the CO
      concentration in flue gas and remained carbon in ash are sufficiently low, and
      organobrominated compounds are successfully decomposed (more than 99.9%).
      According to these results, incineration of waste PCBs without preliminary
      separation and without additives would perform very well under certain
      conditions; the potential precursors for brominated dioxins formation could be
      destroyed efficiently. Increasing temperature could decrease the volume
      percentage ratio of Br(2)/HBr in flue gas greatly.

PMID- 22137321
TI  - The "50% rule".

PMID- 22137322
TI  - Can we detect a clinical difference?

PMID- 22137323
TI  - Three-dimensional stereoscopic anatomy.

PMID- 22137326
TI  - Factors used to determine return to unrestricted sports activities after anterior
      cruciate ligament reconstruction.
AB  - PURPOSE: Anterior cruciate ligament (ACL) reconstruction is commonly performed in
      athletes, with the goal of return to sports activities. Unfortunately, this
      operation may fail, and the rates of either reinjuring an ACL-reconstructed knee
      or sustaining an ACL rupture to the contralateral knee range from 3% to 49%. One
      problem that exists is a lack of information and consensus regarding the
      appropriate criteria for releasing patients to unrestricted sports activities
      postoperatively. The purpose of this study was to determine the published
      criteria used to allow athletes to return to unrestricted sports activities after
      ACL reconstruction. METHODS: A systematic search was performed to identify the
      factors investigators used to determine when return to athletics was allowed
      after primary ACL reconstruction. Inclusion criteria were English language,
      publication within the last 10 years, clinical trial, all adult patients, primary
      ACL reconstruction, original research investigation, and minimum 12 months'
      follow-up. RESULTS: Of 716 studies identified, 264 met the inclusion criteria. Of
      these, 105 (40%) failed to provide any criteria for return to sports after ACL
      reconstruction. In 84 studies (32%) the amount of time postoperatively was the
      only criterion provided. In 40 studies (15%) the amount of time along with
      subjective criteria were given. Only 35 studies (13%) noted objective criteria
      required for return to athletics. These criteria included muscle strength or
      thigh circumference (28 studies), general knee examination (15 studies), single
      leg hop tests (10 studies), Lachman rating (1 study), and validated
      questionnaires (1 study). CONCLUSIONS: The results of this systematic review show
      noteworthy problems and a lack of objective assessment before release to
      unrestricted sports activities. General recommendations are made for
      quantification of muscle strength, stability, neuromuscular control, and function
      in patients who desire to return to athletics after ACL reconstruction, with
      acknowledgment of the need for continued research in this area. LEVEL OF
      EVIDENCE: Level IV, systematic review of Level I to IV studies.

PMID- 22137327
TI  - Making a case for anterior inferior iliac spine/subspine hip impingement: three
      representative case reports and proposed concept.
AB  - Femoroacetabular impingement is typically described as occurring due to a
      conflict between the femoral head-neck junction and acetabular rim. A prior case
      report described an open decompression of the anterior inferior iliac spine
      (AIIS) due to impingement against the proximal femur. AIIS impingement may be
      developmental or the result of a prior AIIS avulsion or pelvic osteotomy. We
      describe 3 representative cases with minimum 1-year follow-up treated with an
      arthroscopic AIIS decompression.

PMID- 22137328
TI  - Candidacidal activities of the glucose oxidase-mediated lactoperoxidase system.
AB  - OBJECTIVE: The purpose of this study was to investigate the candidacidal activity
      of the glucose oxidase-mediated lactoperoxidase system at various levels of
      glucose and glucose oxidase. DESIGN: Candida albicans ATCC strains 18804, 10231,
      11006, bovine lactoperoxidase (25 and 50 MUg/mL), and KSCN (1 mM) were used.
      Different levels of glucose oxidase (1, 5, 10, and 20 units/mL) and glucose
      (0.03, 0.3, and 3.0 mg/mL) were added to complete the system. The candidacidal
      activity of the system was examined by preincubating its components for 0-60 min,
      and then with C. albicans. Candidacidal activity was determined by comparing the
      numbers of CFU and calculating the percent loss of cell viability. RESULTS: The
      system displayed 13.9-27.4% (without preincubation) to 28.6-34.3% (preincubation
      for 60 min) loss of viability at 25 MUg/mL of bovine lactoperoxidase, 10 units/mL
      of glucose oxidase, and 0.03 mg/mL of glucose; similar results were obtained with
      20 units/mL of glucose oxidase or 0.06 mg/mL of glucose. The candidacidal
      activity of the system increased markedly as the glucose concentration increased.
      The candidacidal activity displayed 87.2% (without preincubation) to 100.0%
      (preincubation for 60 min) at 3.0 mg/mL of glucose. At 3.0 mg/mL of glucose, the
      system containing 1 or 5 units of glucose oxidase also showed significant levels
      of candidacidal activity. CONCLUSIONS: The candidacidal activity of the glucose
      oxidase-mediated lactoperoxidase system at physiological concentrations of
      salivary glucose was moderate, but was greatly elevated with increases of glucose
      level.

PMID- 22137329
TI  - Preparation of PLGA scaffolds with graded pores by using a gelatin-microsphere
      template as porogen.
AB  - Porous scaffolds with graded pores are crucial to osteochondral regeneration. In
      this study, a technique combining solution casting with gelatin-microsphere
      template leaching has been developed to produce poly(L-lactide-co-glycolide)
      (PLGA) scaffolds with graded pores. The traditional emulsification and solvent
      extraction method was improved by using the gradient ethanol/water solutions to
      extract water to prepare gelatin microspheres with a smooth surface without the
      use of any surfactant. Gelatin microspheres with different diameters were in
      sequence put into a custom-made cylindrical Teflon mold and bonded together to
      obtain gelatin-microsphere templates. By using the gelatin-microsphere templates
      as porogen, PLGA scaffolds with graded pore size across the cylindrical axis were
      prepared. The porosity of the scaffold was as high as 95%. The pore size effect
      on osteoblasts was studied. The results showed that the graded scaffolds
      possessed good biocompatibility for osteoblast growth. During the 14 days
      culture, the cell proliferation of all the three pore layers displayed the trend
      of increasing. The proliferation rate of the large pore layer was lower than the
      other two layers. However, the difference of alkaline phosphatase activity on the
      three pore layers was not statistically significant. We assumed that it was
      probably because of the hydrophobicity and the short culture time. It was
      demonstrated that gradient ethanol/water solutions provided a simple way to
      prepared gelatin microspheres. The graded scaffolds would provide potential
      application for osteochondral regeneration. 

PMID- 22137330
TI  - Genome-wide study links MTMR7 gene to variant Creutzfeldt-Jakob risk.
AB  - The aim of our study was to discover genomic variations related to variant
      Creutzfeldt-Jakob disease (vCJD) susceptibility. A genome-wide association
      analysis with most vCJD samples available in the world was performed. A series of
      93 vCJD UK patients and 1504 UK controls were included in the discovery stage.
      Our best findings were replicated in an independent population of 22 UK and 20
      French vCJD cases. Post hoc analysis to assess our main results included 5711
      French controls, 445 Dutch controls, and 446 sporadic Creutzfeldt-Jakob disease
      (CJD) cases. We found 2 genome wide significant variants tagging PRNP: rs6107516
      (p = 2.6 * 10(-18)) and rs2065706 (p = 8.8 * 10(-14)). Two other single
      nucleotide polymorphisms (SNPs) (rs4921542 and rs7565981) were successfully
      replicated in independent samples and reached genome-wide significance after
      pooling discovery and replication populations. Rs4921542 (p = 1.6 * 10(-8)) is an
      intronic variant in the myotubularin related protein 7 gene (MTMR7), which is
      specifically expressed in the central nervous system (CNS) and dephosphorylates
      phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. Rs7565981 (p =
      4.2 * 10(-8)) is in an intergenic region upstream of the neuronal PAS (per-ARNT
      sim) domain-containing protein 2 gene (NPAS2), a regulatory gene belonging to a
      family of transcription factors that has been implicated in memory, seasonal
      affective disorder, and the molecular clock in the mammalian forebrain. A proxy
      of rs7565981 (rs17024792; r(2) = 1.0) has been found to regulate the
      phospholipase C-delta-3 gene (PLCD3) in trans. This enzyme catalyzes the
      hydrolysis of phosphatidylinositol 4,5-bisphosphate. Our study reveals 2 new
      genome-wide significant markers for vCJD outside PRNP and provides evidence
      supporting a role of the phosphatidylinositol pathway in vCJD susceptibility.

PMID- 22137331
TI  - Chronic kidney disease and diabetes.
AB  - Chronic kidney disease has a significant worldwide prevalence affecting 7.2% of
      the global adult population with the number dramatically increasing in the
      elderly. Although the causes are various, diabetes is the most common cause of
      CKD in the United States and an increasing cause of the same worldwide.
      Therefore, we chose to focus on diabetic chronic kidney disease in this review.
      The pathogenesis is multifactorial involving adaptive hyperfiltration, advanced
      glycosylated end-product synthesis (AGES), prorenin, cytokines, nephrin
      expression and impaired podocyte-specific insulin signaling. Treatments focus on
      lifestyle interventions including control of hyperglycemia, hypertension and
      hyperlipidemia as well treatment of complications and preparation for renal
      replacement therapy. This review examines the current literature on the
      epidemiology, pathogenesis, complications and treatment of CKD as well as
      possible areas of future disease intervention.

PMID- 22137332
TI  - Music therapy for dementia.

PMID- 22137333
TI  - Methylation status of the E2 binding sites of HPV16 in cervical lesions
      determined with the Luminex(r) xMAPTM system.
AB  - Cervical carcinogenesis is driven by deregulated E6/E7 expression in dividing
      cells. A potential deregulating mechanism is methylation of E2 binding sites in
      the viral long control region, thereby prohibiting HPVE2-mediated transcription
      regulation. Here the frequency of HPV16E2BS methylation in cervical lesions (SCC,
      n=29; CIN3, n=17) and scrapes (controls, n=17; CIN3, n=21) was investigated.
      Three E2BSs were amplified using methylation independent PCR followed by specific
      detection of methylated CpGs using the Luminex(r) xMAPTM system. The frequency of
      E2BS1, E2BS3 and E2BS4 methylation was significantly higher in SCC compared to
      CIN3, i.e. 93% vs. 21% (p<0.01), 90% vs. 47% (p<0.01) and 69% vs. 5% (p<0.01),
      respectively and ranged from 6 to 15% in controls. In scrapings of women with
      CIN3 methylation ranged from 24 to 33%. In conclusion, we showed that the MIP
      Luminex system is a highly sensitive method for methylation analysis. HPV16 E2BSs
      methylation appeared highly frequent in SCC, with particularly E2BS3 methylation
      occurring proportional to severity of cervical disease.

PMID- 22137334
TI  - Long term stability of mandibular advancement procedures: bilateral sagittal
      split osteotomy versus distraction osteogenesis.
AB  - The aim of this study was to compare the postoperative stability of the mandible
      after a bilateral lengthening procedure, either by bilateral sagittal split
      osteotomy (BSSO) or distraction osteogenesis (DO). All patients who underwent
      mandibular advancement surgery between March 2001 and June 2004 were evaluated.
      There were 17 patients in the BSSO group and 18 patients in the DO group. The
      decision to use intra-oral distraction or BSSO for mandibular advancement
      primarily depended on the choice of the patient and their parents. In both
      groups, standardized cephalometric radiographs were taken preoperatively,
      postoperatively (BSSO group) or directly post-distraction (DO group) and during
      the last study measurement in May 2008. Cephalometric analysis was performed
      using the following measurements: sella/nasion-mandibular point B and
      sella/nasion-mandibular plane. Point B was used to estimate relapse. This study
      showed no significant difference in relapse between the BSSO and the DO groups
      measured 46-95 months after advancement of the mandible (P>.05). It can be
      concluded from this study that there is no postoperative difference in the
      stability between BSSO and DO after mandibular advancement after 4 years.

PMID- 22137335
TI  - Morphological features of the maxillary incisors roots and relationship with
      neighbouring anatomical structures: possible implications in endodontic surgery.
AB  - The purpose of this study was to investigate the relationship between the root
      apex of the upper incisors and neighbouring anatomical structures as well as the
      morphology of the root-end foramen after apicoectomy. Fifty-seven patients
      requiring endodontic surgical treatment for a maxillary anterior root were
      enrolled. A preoperative diagnostic computed tomography (CT) scan was analysed to
      determine: the distance between the anterior wall of the nasopalatine duct and
      the central (CI-ND) incisor root 4mm from the apex; and the distance between the
      floor of the nasal cavity and the tip of either the central (CI-NF) or the
      lateral (LI-NF) incisor root. After apicoectomy, root-end foramen endoscopic
      pictures were taken in order to characterize their morphology. Fifty-nine central
      and 26 lateral incisors were evaluated. The average CI-ND was 4.71 +/- 1.26 (SD)
      mm. The average CI-NF was 10.62 +/- 2.25 mm. The average LI-NF was 13.05 +/- 2.43
      mm. The foramen shape after apicoectomy was ovoid to circular in about 90% of
      cases in both central and lateral incisors. A sound knowledge of the anatomical
      relationships at the surgical site is essential for the clinician to perform a
      safe endodontic surgical procedure.

PMID- 22137336
TI  - Sensory axon regeneration: rebuilding functional connections in the spinal cord.
AB  - Functional regeneration within the adult spinal cord remains a formidable task. A
      major barrier to regeneration of sensory axons into the spinal cord is the dorsal
      root entry zone. This region displays many of the inhibitory features
      characteristic of other central nervous system injuries. Several experimental
      treatments, including inactivation of inhibitory molecules (such as Nogo and
      chondroitin sulfate proteoglycans) or administration of neurotrophic factors
      (such as nerve growth factor, neurotrophin3, glial-derived neurotrophic factor
      and artemin), have been found to promote anatomical and functional regeneration
      across this barrier. However, there have been relatively few experiments to
      determine whether regenerating axons project back to their appropriate target
      areas within the spinal cord. This review focuses on recent advances in sensory
      axon regeneration, including studies assessing the ability of sensory axons to
      reconnect with their original synaptic targets.

PMID- 22137338
TI  - [Postoperative abdominal adhesions and their prevention in gynaecological
      surgery: II. How can they be prevented?].
AB  - This paper is the second of a two-part publication. The initial paper provided a
      comprehensive overview of the evidence on adhesions to allow gynaecological
      surgeons to be best informed on adhesions, their development, impact on patients,
      health systems and surgical outcomes. There is rising evidence that surgeons can
      take important steps to reduce the burden of adhesions. In this second paper, we
      review the various strategies to reduce the impact of adhesions, improve surgical
      outcomes and provide some practical proposals for action on adhesions. As well as
      improvements in surgical technique, developments in adhesion-reduction strategies
      and new agents offer a realistic possibility of reducing adhesion formation and
      improving outcomes for patients. They should be considered for use particularly
      in high-risk surgery and in patients with adhesiogenic conditions. Further
      research into new strategies to prevent adhesions more effectively through an
      improved surgical environment, new and combination devices and pharmacological
      agents should be encouraged. Formal recommendations would ensure better
      prioritisation of adhesion-reduction within the French health system. Patients
      should also be better informed of the risks of adhesions.

PMID- 22137339
TI  - Design, synthesis and in vitro evaluation of novel bivalent S-adenosylmethionine
      analogues.
AB  - In optimal cases, bivalent ligands can bind with exceptionally high affinity to
      their protein targets. However, designing optimised linkers, that orient the two
      binding groups perfectly, is challenging, and yet crucial in both fragment-based
      ligand design and in the discovery of bisubstrate enzyme inhibitors. To further
      our understanding of linker design, a series of novel bivalent S
      adenosylmethionine (SAM) analogues were designed with the aim of interacting with
      the MetJ dimer in a bivalent sense (1:1 ligand/MetJ dimer). A range of ligands
      was synthesised and analyzed for ability to promote binding of the Escherichia
      coli methionine repressor, MetJ, to its operator DNA. Binding of bivalent SAM
      analogues to the MetJ homodimer in the presence of operator DNA was evaluated by
      fluorescence anisotropy and the effect of linker length and structure was
      investigated. The most effective bivalent ligand identified had a flexible
      linker, and promoted the DNA-protein interaction at 21-times lower concentration
      than the corresponding monovalent control compound.

PMID- 22137340
TI  - Discovery of estrogen receptor alpha modulators from natural compounds in Si-Wu
      Tang series decoctions using estrogen-responsive MCF-7 breast cancer cells.
AB  - The binding between the estrogen receptor alpha (ER-alpha) and a variety of
      compounds in traditional Chinese formulae, Si-Wu-Tang (SWT) series decoctions,
      was studied using a stably-transfected human breast cancer cell line (MVLN). In
      38 compounds tested from SWT series decoctions, the estrogen-like activity of 22
      compounds was above 60% in 20 MUg mL(-1). Furthermore, theoretical affinity of
      these compounds was certificated using the functional virtual screen of ER-alpha
      modulators by FlexX-Pharm. The accuracy of functional virtual screening of ER
      alpha modulators could reach to 77.27%. The results showed that some compounds,
      such as organic acids and flavones in SWT series decoctions could be used as
      selective estrogen receptor modulators (SERMs) and could be selected for further
      development as potential agents for estrogen related diseases.

PMID- 22137337
TI  - Prion protein at the crossroads of physiology and disease.
AB  - The presence of the cellular prion protein (PrP(C)) on the cell surface is
      critical for the neurotoxicity of prions. Although several biological activities
      have been attributed to PrP(C), a definitive demonstration of its physiological
      function remains elusive. In this review, we discuss some of the proposed
      functions of PrP(C), focusing on recently suggested roles in cell adhesion,
      regulation of ionic currents at the cell membrane and neuroprotection. We also
      discuss recent evidence supporting the idea that PrP(C) may function as a
      receptor for soluble oligomers of the amyloid beta peptide and possibly other
      toxic protein aggregates. These data suggest surprising new connections between
      the physiological function of PrP(C) and its role in neurodegenerative diseases
      beyond those caused by prions.

PMID- 22137341
TI  - Identification of oxazolidinediones and thiazolidinediones as potent 17beta
      hydroxysteroid dehydrogenase type 3 inhibitors.
AB  - Novel and potent inhibitors of 17beta-hydroxysteroid dehydrogenase type 3 (17beta
      HSD3) were identified based on oxazolidinedione and thiazolidinedione
      derivatives, starting from a high-throughput screening hit, 5-(3-bromo-4
      hydroxybenzyl)-3-(4-methoxyphenyl)-1,3-thiazol-2-one. 5-(3-Bromo-4
      hydroxybenzylidene)-3-(4-methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one exhibited
      a promising activity profile and demonstrated significant selectivity over the
      related 17beta-HSD isoenzymes and nuclear receptors.

PMID- 22137342
TI  - Discovery and optimization of thieno[2,3-d]pyrimidines as B-Raf inhibitors.
AB  - The serine/threonine specific protein kinase B-Raf is part of the MAPK pathway
      and is an interesting oncology target. We have identified thieno[2,3
      d]pyrimidines as a core scaffold of small molecule B-Raf inhibitors. The SAR of
      analogs in this series will be described.

PMID- 22137343
TI  - Development of phyllanthin containing microcapsules and their improved biological
      activity towards skin cells and Staphylococcus aureus.
AB  - Chitosan based microcapsule which encapsulated with phyllanthin was developed by
      simple coacervation. The composition and surface morphology of phyllanthin
      containing microcapsules were analyzed by Fourier Transform Infrared spectroscopy
      and Scanning Electron Microscopy, respectively. The release of phyllanthin from
      the microcapsules was found to be more than 60% after 120 h. In vitro biological
      assays demonstrated that these phyllanthin containing microcapsules showed a
      stronger anti-oxidation potential on both human fibroblasts and keratinocytes as
      well as a better growth inhibitory activity towards Staphylococcus aureus.

PMID- 22137344
TI  - Synthesis and anticonvulsant evaluation of some new 2,3,8-trisubstituted-4(3H)
      quinazoline derivatives.
AB  - A new series of 2,3,8-trisubstituted-4(3H)-quinazoline derivatives were
      synthesized, evaluated for their anticonvulsant activity against electrically
      (MES) and chemically (PTZ, picrotoxin and Strychnine) induced seizures and
      compared with the standard drugs methaqualone and sodium valproate. Compounds 3,
      17 and 22 proved to be the most potent compounds of this series with relatively
      low neurotoxicity and low toxicity in the median lethal dose test as compared
      with the reference drugs. The obtained results showed that the most active
      compounds could be useful as a template for future design, modification and
      investigation to produce more active analogs.

PMID- 22137345
TI  - 5- and 6-membered (thio)lactones are prodrug type carbonic anhydrase inhibitors.
AB  - The inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) with
      (thio)coumarins has been recently reported (Maresca et al., J. Am. Chem. Soc.
      2009, 131, 3057). Here we demonstrate that a series of gamma- and delta
      (thio)lactones also act as mechanism based, prodrug type CA inhibitors, similar
      to the (thio)coumarins. Through the esterase activity of CA, these compounds are
      hydrolyzed in situ to the corresponding hydroxy/keto/mercapto acids which
      thereafter act as inhibitors. CA isoforms I and IX were efficiently inhibited by
      simple such compounds, with K(I)s in the range of 0.92-19.1MUM, whereas CA II was
      not inhibited at all. Isoform-selective CA inhibitors which spare the ubiquitous
      off-target CA II may have interesting applications for example for selectively
      inhibiting the tumor-associated CA IX, a validated anticancer target.

PMID- 22137346
TI  - Trials for the control of trichodinosis and gyrodactylosis in hatchery reared
      Oreochromis niloticus fries by using garlic.
AB  - The present work was designed to study the prevalence of trichodinosis and
      gyrodactylosis in Oreochromis niloticus fries, and to test the therapeutic
      efficacy and preventive efficacy of garlic oil and crushed garlic cloves.
      Trichodinosis and gyrodactylosis are ectoparasitic diseases that affect most warm
      freshwater fish, especially fries and fingerlings. In a private O. niloticus fish
      hatchery, the prevalence of trichodinosis in 5-, 15- and 30-day-old-fries was
      37%, 23% and 40.5%, respectively. The highest infection intensity was detected in
      30-day-old-fries. The gyrodactylosis was reported only in combination with
      trichodinosis. In addition, we found that its prevalence in 5-, 15- and 30-day
      old-fries was 17%, 19.5% and 29%, respectively. Mortality rate of fry in the
      first month of life was 53% as a result of injury to these two types of
      parasites. The garlic oil and crushed garlic cloves were tested in both in vitro
      and earthen ponds of the hatchery. Using 2-, 2.5- and 3-ppt (parts per thousand)
      garlic oil for 4h in vitro water bath treatment resulted in 100% recovery, while
      1 and 1.5 ppt garlic oil, respectively, needed 24 and 16 h to treat the infected
      fries. The treatment by 3 ppt garlic oil as a water bath for 1h treated the two
      diseases in 55% in 7 days from application in the hatchery earthen pond. In the
      mean time, 300 mg L(-1) crushed garlic cloves as an indefinite bath in the
      hatchery earthen pond eliminated 68% of the diseases. The same protocol for
      preventing the two diseases resulted in obtaining 65% and 75% of parasite free
      fries, for garlic oil and crushed garlic cloves, respectively, compared to 53% of
      the control fries.

PMID- 22137347
TI  - Humoral and cellular immune responses in pigs immunized intranasally with crude
      rhoptry proteins of Toxoplasma gondii plus Quil-A.
AB  - We evaluated the humoral and cellular immune responses in pigs immunized
      intranasally with crude rhoptry proteins of Toxoplasma gondii plus Quil-A. The
      experiment used 13 mixed-breed pigs divided into the following three groups: G1
      (vaccinated-challenged, n=6), which received the rhoptry vaccine (200(g/dose); G2
      (adjuvant-challenged, n=4), which received PBS plus Quil-A; and G3 (unvaccinated
      challenged, n=3), which was the control group. The treatments were performed
      intranasally at days 0, 21, and 42. Three pigs from G1 produced IgG and IgM
      antibody levels above the cut-off in the ELISA on the challenge day. Partial
      protection was observed in G1 at the chronic phase of infection when compared
      with G3. The preventable fractions were 41.6% and 6.5%, in G1 and G2,
      respectively. The results of this study suggest that rhoptry proteins plus Quil-A
      stimulated humoral, local, and systemic immune responses, which were able to
      partially protect the brain from cyst formation.

PMID- 22137348
TI  - The opportunistic Sarcoptes scabiei: a new episode from giraffe in the drought
      suffering Kenya.
AB  - The ubiquitous Sarcoptes mite is unexplainable emerging and re-emerging parasite,
      threatening biodiversity and human health. When a new outbreak occurs, it is not
      clear if it is a genuine emergence resulting from a new incidence or apparent
      emergence resulting from increased detection. In this paper we report, for the
      first time to our knowledge, an outbreak of sarcoptic mange in giraffes in the
      wild. Three decaying carcasses and five free-ranging subadult reticulated
      giraffes were observed to have mange-like lesions in the drought-suffering Wajir
      Region in North Eastern Kenya, while apparently all sympatric wild and domestic
      animals were mange-free. Affected giraffes were captured and successfully
      treated. The possible relations between this outbreak and annual seasons, animal
      age-classes and sex, and spatial distribution are discussed.

PMID- 22137349
TI  - Acaricidal activity of hydroethanolic formulations of thymol against
      Rhipicephalus sanguineus (Acari: Ixodidae) and Dermacentor nitens (Acari:
      Ixodidae) larvae.
AB  - The aim of this study was to assess the acaricidal activity of hydroethanolic
      formulations of thymol at varying concentrations on Rhipicephalus sanguineus and
      Dermacentor nitens larvae. The larval packet test was used and the thymol
      concentrations tested were 2.5, 5.0, 10.0, 15.0 and 20.0 mg/ml. The control group
      was exposed only to water and ethanol (50/50%) and there were 10 repetitions for
      each treatment. The mortality was evaluated after 24 h. For the R. sanguineus
      larvae, the mortality rates were 47.5, 50.2, 96.7, 95.9 and 98.1%, while for D.
      nitens the rates were 14.1, 75.0, 90.2, 90.3 and 99.5%, at respective thymol
      concentrations of 2.5, 5.0, 10.0, 15.0 and 20.0 mg/ml. The results indicate that
      the hydroethanolic formulations of thymol tested have acaricidal activity on R.
      sanguineus and D. nitens larvae exposed topically, causing mortality greater than
      90% 24 h post-treatment starting at the concentration of 10 mg/ml.

PMID- 22137350
TI  - Phenology and attraction of potential Culicoides vectors of bluetongue virus in
      Basque Country (northern Spain).
AB  - Bluetongue virus is transmitted by Culicoides biting midges (Diptera:
      Ceratopogonidae). Culicoides associated with livestock were captured using CDC
      blacklight traps at three BTV-infected farms in Basque Country between November
      2007 and December 2008. Twenty-seven and nineteen Culicoides species were
      collected in outdoor and indoor habitats respectively. Indoor insect community
      represented 86.1% of the whole captured individual biting midges. Culicoides
      obsoletus/Culicoides scoticus (two sibling species of the Obsoletus complex) were
      dominant throughout all months and sexes with maximum phenological peaks in
      November 2007 and June-July 2008. Culicoides lupicaris was the second most
      dominant species followed by Culicoides pulicaris (both species of the Pulicaris
      complex). Few specimens of Culicoides imicola, the principal Afro-Mediterranean
      vector of BTV, as well as four new species recorded for the Iberian Peninsula,
      were also collected. BTV was detected by RT-PCR from pools of C. obsoletus/C.
      scoticus, C. lupicaris and C. pulicaris parous females. DL-Lactic acid
      significantly attracted more C. obsoletus/C. scoticus females and males, C.
      lupicaris females, C. pulicaris females and Culicoides punctatus females and
      males; whereas acetone increased only the captures of Culicoides achrayi.

PMID- 22137353
TI  - Advances in preoperative risk assessment and management.

PMID- 22137355
TI  - TRACK-HD: both promise and disappointment.

PMID- 22137354
TI  - Potential endpoints for clinical trials in premanifest and early Huntington's
      disease in the TRACK-HD study: analysis of 24 month observational data.
AB  - BACKGROUND: TRACK-HD is a prospective observational biomarker study in
      premanifest and early Huntington's disease (HD). In this report we define a
      battery of potential outcome measures for therapeutic trials. METHODS: We
      assessed longitudinal data collected at baseline, 12 months, and 24 months at
      sites in Leiden (Netherlands), London (UK), Paris (France), and Vancouver
      (Canada). Participants were individuals without HD but carrying the mutant HTT
      gene (ie, premanifest HD), patients with early HD, and healthy control
      individuals matched by age and sex to the combined HD groups. Data were collected
      with 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and
      neuropsychiatric assessments. We estimated adjusted, between-group differences in
      rates of change in these measures and concomitant longitudinal effect sizes.
      FINDINGS: Longitudinal data were available for 116 control individuals, 117
      premanifest gene carriers, and 116 participants with early HD. Significantly
      greater progressive grey-matter, white-matter, whole-brain, and regional atrophy
      was recorded in the premanifest and early HD groups than in the control group.
      Effect sizes for atrophy rates between participants with early HD and controls
      were largest in the caudate (2.04, 95% CI 1.68 to 2.48) and white matter (1.70,
      1.40 to 2.08). Functional, quantitative motor, and cognitive measures
      deteriorated to a greater extent in the early HD group than in controls, with the
      largest effect size in the symbol digit modality test (1.00, 0.67 to 1.27). In
      the early HD group, changes in structural imaging and various cognitive and
      quantitative motor scores were associated with worsening total motor score (TMS)
      and total functional capacity (TFC). In the premanifest group, despite
      significant declines in regional and overall brain volumes, few functional
      variables showed significant 24 month change compared with controls; TMS, emotion
      recognition, and speeded tapping were exceptions. Premanifest individuals with
      progression, predefined as an increase in TMS score of 5 points or more, any TFC
      decline, or a new diagnostic confidence score of 4, exhibited higher rates of
      brain atrophy and deterioration on some quantitative motor tasks compared with
      other premanifest participants. INTERPRETATION: On the basis of longitudinal
      effect size, we recommend several objective outcome measures for clinical trials
      in participants with early HD. Hypothetical treatment effects defined by slower
      longitudinal changes in these measures would be detectable over a realistic
      timescale with practical sample sizes. The restricted 24 month cognitive or motor
      decline in the premanifest sample illustrates the greater challenge in trial
      design for this group. FUNDING: CHDI/HighQ Foundation Inc.

PMID- 22137356
TI  - An unlikely role for the NAT2 genotypes and haplotypes in the oral cancer of
      south Indians.
AB  - The arylamine N-acetyltransferase 2 (NAT2) enzyme detoxifies a wide spectrum of
      naturally occurring xenobiotics including carcinogens and drugs. Acetylation
      catalysed by the NAT2 is an important process in metabolic activation of
      arylamines to electrophilic intermediates that initiate carcinogenesis.
      Polymorphism in N-acetyltransferase 2 gene was reported to be associated with the
      susceptibility of various cancers. OBJECTIVE: The aim of our study was to
      determine whether there is any association between the susceptibility to oral
      cancer amongst the variations of NAT2 genotypes. DESIGN: This study was carried
      out in 157 patients with oral cancer. The control group consisted of 132 healthy
      volunteers. The most common polymorphisms rs1799929, rs1799930 and rs1799931 on
      the NAT2 gene were screened for the genotypes using TaqMan allelic
      discrimination. RESULTS: All the three SNPs were polymorphic with minor allele
      frequency of 0.339, 0.372 and 0.061 for rs1799929, rs1799930 and rs1799931,
      respectively. None of the polymorphic site deviated from HWE in controls. There
      were no significant differences in genotype or allele frequencies of three SNPs
      between controls and cases with oral cancer. Risk of oral cancer development for
      the carriers of the individual deduced phenotypes was also not statistically
      significant. Of the 3 studied polymorphisms, 2 were in strong LD and form one
      haplotype block. None of the haplotype had shown significant association with the
      oral cancer. CONCLUSIONS: Our study concludes that the NAT2 genotypes, phenotypes
      and haplotypes are not involved in the susceptibility to oral cancer in South
      Indian subjects.

PMID- 22137357
TI  - Polyfluorinated compounds in the atmosphere along a cruise pathway from the Japan
      Sea to the Arctic Ocean.
AB  - Neutral polyfluorinated alkyl substances (PFASs) were measured in high-volume air
      samples collected on board the research vessel Snow Dragon during the 4th Chinese
      National Arctic Expedition from the Japan Sea to the Arctic Ocean in 2010. Four
      volatile and semi-volatile PFASs (fluorotelomer alcohols (FTOHs), fluorotelomer
      acids (FTAs), perfluoroalkyl sulfonamides (FASAs), and sulfonamidoethanols
      (FASEs)) were analyzed respectively in the gas and particle phases. FTOHs were
      the dominant PFASs in the gas phase (61-358pgm(-3)), followed by FTAs (5.2
      47.9pgm(-3)), FASEs (1.9-15.0pgm(-3)), and FASAs (0.5-2.1pgm(-3)). In the
      particle phase, the dominant PFAS class was FTOHs (1.0-9.9pgm(-3)). The particle
      associated fraction followed the general trend of FASEs>FASAs>FTOHs. Compared
      with other atmospheric PFAS measurements, the ranges of concentrations of ?FTOH
      in this study were similar to those reported from Toronto, north America (urban),
      the northeast Atlantic Ocean, and northern Germany. Significant correlations
      between FASEs in the gas phase and ambient air temperature indicate that cold
      surfaces such as sea-ice, snowpack, and surface seawater influence atmospheric
      FASEs.

PMID- 22137358
TI  - Direct and indirect photolysis of two quinolinecarboxylic herbicides in aqueous
      systems.
AB  - The photodegradation of two quinolinecarboxylic herbicides, 7-chloro-3
      methylquinoline-8-carboxylic acid (QMe) and 3,7-dichloroquinoline-8-carboxylic
      acid (QCl), was studied in aqueous solution at different irradiation wavelengths.
      The effect of sunlight irradiation was investigated also in the presence of
      titanium dioxide (TiO(2)). UV irradiation degraded rapidly QMe affording 7-chloro
      3-methylquinoline (MeQ) through a decarboxylation reaction. The reaction rate was
      lower in the presence of dissolved organic carbon (DOC) because of the adsorption
      of the herbicide on the organic components. Instead, QCl was stable under both UV
      light and sunlight irradiation. The irradiation of QMe or QCl solutions with
      simulated sunlight in the presence of TiO(2) produced the complete mineralization
      of the two herbicides.

PMID- 22137359
TI  - [Present and future of the formation MIR of Endocrinology and Nutrition].

PMID- 22137360
TI  - Relative toxicity of the components of the original formulation of Roundup to
      five North American anurans.
AB  - The responses of five North American frog species that were exposed in an aqueous
      system to the original formulation of Roundup were compared. Carefully designed
      and un-confounded laboratory toxicity tests are crucial for accurate assessment
      of potential risks from the original formulation of Roundup to North American
      amphibians in aquatic environments. The formulated mixture of this herbicide as
      well as its components, isopropylamine (IPA) salt of glyphosate and the
      surfactant MON 0818 (containing polyethoxylated tallowamine (POEA)) were
      separately tested in 96 h acute toxicity tests with Gosner stage 25 larval
      anurans. Rana pipiens, R. clamitans, R. catesbeiana, Bufo fowleri, and Hyla
      chrysoscelis were reared from egg masses and exposed to a series of 11
      concentrations of the original formulation of Roundup herbicide, nine
      concentrations of MON 0818 and three concentrations of IPA salt of glyphosate in
      static (non-renewal) aqueous laboratory tests. LC50 values are expressed as
      glyphosate acid equivalents (ae) or as mg/L for MON 0818 concentrations for
      comparison between the formulation and components. R. pipiens was the most
      sensitive of five species with 96 h-LC50 values for formulation tests, for the
      five species, ranging from 1.80 to 4.22 mg ae/L, and MON 0818 exposures with 96 h
      LC50 values ranging from 0.68 to 1.32 mg/L. No significant mortality was observed
      during exposures of 96 h for any of the five species exposed to glyphosate IPA
      salt at concentrations up to 100 times the predicted environmental concentration
      (PEC). These results agree with previous studies which have noted that the
      surfactant MON 0818 containing POEA contributes the majority of the toxicity to
      the herbicide formulations for fish, aquatic invertebrates, and amphibians. These
      study results suggest that anurans are among the most sensitive species, and
      emphasize the importance of testing the herbicide formulation in addition to its
      separate components to accurately characterize the toxicity and potential risk of
      the formulation.

PMID- 22137361
TI  - Implementation of a minimal set of biological tests to assess the ecotoxic
      effects of effluents from land-based marine fish farms.
AB  - Environmental monitoring plans (EMP) that include chemical analysis of water, a
      battery of bioassays and the study of local hydrodynamic conditions are required
      for land-based marine aquaculture. In this study, the following standardized
      toxicity tests were performed to assess the toxicity of effluents from eight land
      base marine fish farms (LBMFFs) located on the northwest coast of Spain:
      bacterial bioluminescence (with Vibrio fischeri at 15 and 30 min), microalgal
      growth (with Phaeodactyllum tricornutum and Isochrysis galbana) and sea urchin
      larval development (with Paracentrotus lividus and Arbacia lixula). These
      bioassays were evaluated for inclusion in routine fish farm monitoring. Effective
      concentrations (EC(5), EC(10), EC(20), EC(50)) for each bioassay were calculated
      from dose-response curves, obtained by fitting the bioassay results to the best
      parametric model. Moreover, a graphical method of integrating the results from
      the battery of bioassays and classifying the toxicity was proposed, and the
      potential ecotoxic effects probe (PEEP) index was calculated. The bacterial
      bioluminiscence test at 30min, growth of I. galbana and larval development of A.
      lixula were found to be the most sensitive and useful tests. Graphical
      integration of these test results enabled definition of the ecotoxicological
      profiles of the different farms. The PEEP index, considering EC(20), efficiently
      reflected the toxic loading potential of LBMFF effluents. In conclusion, a
      battery of bioassays with species from different low trophic levels is
      recommended as a rapid and cost-effective methodology for assessing LBMFF
      discharges. The graphical integration method and the PEEP index are proposed for
      consideration in EMPs for such farms.

PMID- 22137363
TI  - Diabetic retinopathy screening in patients with diabetes mellitus in primary
      care: Incentives and barriers to screening attendance.
AB  - AIM: Although diabetic retinopathy (DR) screening is a basic component of
      diabetes care, uptake of screening programs is less than optimal. Because
      attendance rates and reasons for non-attendance in an unselected diabetes
      population are unknown, this study examines incentives and barriers to attend DR
      screening. METHOD: Four focus groups provided patient-related themes concerning
      individual decision-making regarding attendance at DR-screening. A questionnaire
      measuring attendance rates and the influence of several factors was sent to 3236
      diabetes patients (>18 years) in 20 Dutch general practices, of which 2363 (73%)
      responded. RESULTS: In the past 3 years, 81% of the patients had attended DR
      screening. Patients not attending had lower levels of education, a more recent
      diagnosis of diabetes, and less frequently used insulin. There was no difference
      in DM types 1 and 2 patients regarding attendance. Patients attending more often
      visited health-care providers. Patients reported 'knowledge of detrimental
      effects of DR on visual acuity', 'sense of duty' and 'fear of impaired vision' as
      main incentives. The main barrier was the absence of a recommendation by the
      health-care provider. CONCLUSION: Knowledge about detrimental effects of DR on
      visual acuity and recommendation by health-care providers are important, possibly
      modifiable, factors in the attendance to DR screening.

PMID- 22137362
TI  - Decrease in calcium-sensing receptor in the progress of diabetic cardiomyopathy.
AB  - To observe the dynamic expression of calcium-sensing receptor (CaSR) in
      myocardium of diabetic rats and explore its role in diabetic cardiomyopathy
      (DCM), 40 male Wistar rats were randomly divided into 4 groups including control,
      diabetic-4 weeks, diabetic-8 weeks and spermine treatment groups (240 MUM of
      spermine in drinking water). The type 2 Diabetes mellitus (DM) models were
      established by intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) after
      high-fat and high-sugar diet for one month. The echocardiographic parameters were
      measured, cardiac morphology was observed by electron microscope and HE staining.
      The intracellular calcium concentration ([Ca(2+)](i)) was detected by laser
      scanning confocal microscope. Western blot analyzed the expression of CaSR,
      protein kinase C alpha(PKC-alpha) and calcium handling regulators, such as
      phospholamban (PLN), Ca(2+)-ATPase (SERCA), and ryanodine receptor (RyR).
      Compared with control group, [Ca(2+)](i) and the expression of CaSR, RyR and
      SERCA/PLN were decreased, while PKC-alpha and PLN were significantly increased in
      a time-dependent manner in diabetic groups. Meanwhile diabetic rats displayed
      abnormal cardiac structure and systolic and diastolic dysfunction, and spermine
      (CaSR agonist) could prevent or slow its progression. These results indicate that
      the CaSR expression of myocardium is reduced in the progress of DCM, and its
      potential mechanism is related to the impaired intracellular calcium homeostasis.

PMID- 22137364
TI  - The validation of an active control intervention for Mindfulness Based Stress
      Reduction (MBSR).
AB  - Most of the extant literature investigating the health effects of mindfulness
      interventions relies on wait-list control comparisons. The current article
      specifies and validates an active control condition, the Health Enhancement
      Program (HEP), thus providing the foundation necessary for rigorous
      investigations of the relative efficacy of Mindfulness Based Stress Reduction
      (MBSR) and for testing mindfulness as an active ingredient. 63 participants were
      randomized to either MBSR (n = 31) or HEP (n = 32). Compared to HEP, MBSR led to
      reductions in thermal pain ratings in the mindfulness- but not the HEP-related
      instruction condition (eta(2) = .18). There were significant improvements over
      time for general distress (eta(2) = .09), anxiety (eta(2) = .08), hostility
      (eta(2) = .07), and medical symptoms (eta(2) = .14), but no effects of
      intervention. Practice was not related to change. HEP is an active control
      condition for MBSR while remaining inert to mindfulness. These claims are
      supported by results from a pain task. Participant-reported outcomes (PROs)
      replicate previous improvements to well-being in MBSR, but indicate that MBSR is
      no more effective than a rigorous active control in improving these indices.
      These results emphasize the importance of using an active control condition like
      HEP in studies evaluating the effectiveness of MBSR.

PMID- 22137365
TI  - How awkward! Social anxiety and the perceived consequences of social blunders.
AB  - Seventy high socially anxious (HSA) and 74 low socially anxious (LSA)
      participants rated perceived interpersonal and emotional consequences of both (a)
      autobiographical social blunders recalled from their own lives and (b) imagined
      blunders presented in standardized hypothetical social scenarios. Ratings of
      participants' autobiographical blunders were also provided by research assistants
      who were blind to hypotheses. Results indicated that HSA participants
      overestimated the negative consequences of their own autobiographical blunders.
      These negative perceptions among HSA participants extended to imagined blunders,
      even when participants were instructed to imagine a third party other than
      themselves as the person committing the blunder. This pattern of results suggests
      the conclusion that the perceived consequences of social blunders among HSA
      individuals are driven by the belief that social standards are high, inflexible,
      or both.

PMID- 22137366
TI  - Effects of an Internet-based intervention for subthreshold eating disorders: a
      randomized controlled trial.
AB  - BACKGROUND: Women reporting initial eating disorder (ED) symptoms are at highest
      risk for the development of an eating disorder. Preventive interventions should,
      therefore, be specifically tailored for this subgroup. AIMS: To adapt and
      evaluate the effects of the Internet-based prevention program "Student BodiesTM"
      for women with symptoms of disordered eating and/or subthreshold eating disorder
      (ED) syndromes. METHOD: 126 women, reporting subthreshold ED symptoms (high
      weight and shape concerns and below threshold bingeing, purging, chronic dieting
      or several of these symptoms) were randomly assigned to a Student BodiesTM+ (SB+)
      intervention or a wait-list control group and assessed at pre-intervention, post
      intervention, and 6-month follow-up. "Student BodiesTM" was adapted to be
      suitable for subthreshold EDs. Main outcome measures were attitudes and symptoms
      of disordered eating. Pre-follow-up data were analyzed by ANCOVAS with mixed
      effects. RESULTS: At 6-month follow-up, compared to participants in the control
      group, participants in the intervention group showed significantly greater
      improvements on ED-related attitudes. Intervention participants also showed 67%
      (95% CI = 20-87%) greater reductions in combined rates of subjective and
      objective binges, and 86% (95% CI = 63-95%) greater reduction in purging
      episodes. Also, the rates of participants abstinent from all symptoms of
      disordered eating (restrictive eating, binge eating and any compensatory
      behavior) were significantly higher in the intervention group (45.1% vs. 26.9%).
      Post-hoc subgroup analyses revealed that for participants with binge eating the
      effect on EDE-Q scores was larger than in the pure restricting subgroup.
      CONCLUSION: The adapted "SB+" program represents an effective intervention for
      women with subthreshold EDs of the binge eating subtype.

PMID- 22137367
TI  - A pilot study of discontinuous, insulin-like growth factor 1-dosing growth
      hormone treatment in young children with FGFR3 N540K-mutated hypochondroplasia.
AB  - OBJECTIVE: To assess the growth promoting effect of a recombinant growth hormone
      (rGH) treatment protocol adjusted on insulin-like growth factor 1 (IGF-1) dosing
      in children affected by the most severe forms of FGFR3 N540K-mutated
      hypochondroplasia. STUDY DESIGN: Midterm results of an open-label, single-center,
      nonrandomized, 2003-2020 pilot trial to final stature, including 6 children (mean
      age, 2.6 +/- 0.7 years; mean height SDS, -3.0 +/- 0.5) with the N540K mutation of
      FGFR3 gene who received an rGH dosage titrated to an IGF-1 level close to 1.5 SDS
      of the normal range. rGH therapy was interrupted 1 day per week, 1 month per
      year, and 6 months every 2 years. RESULTS: The mean height SDS increased by 1.9
      during the 6.1 +/- 0.9-year study period, reaching -0.8 to -1.3 at age 8.7 +/- 1
      years. The mean+/-SDS baseline IGF-1 value was -1.6 +/- 0.5 before rGH treatment
      and 1.4+/-0.3 during the last year of observation. The average cumulative rGH
      dose was 0.075 +/- 0.018 mg/kg/day (range, 0.059-0.100 mg/kg/day). Trunk/leg
      disproportion was improved. CONCLUSION: IGF-1-dosing rGH treatment durably
      improves growth and reduces body disproportion in children with severe forms of
      hypochondroplasia.

PMID- 22137368
TI  - Human papillomavirus genotypes present in the oral mucosa of newborns and their
      concordance with maternal cervical human papillomavirus genotypes.
AB  - OBJECTIVES: To elucidate the concordance of human papillomavirus (HPV) genotypes
      between the mother and her newborn and to identify risk factors for the vertical
      transmission of HPV. STUDY DESIGN: HPV genotypes present in 329 pregnant women,
      their newborns, cord blood, and placenta samples were determined by molecular
      techniques, including using pure DNA for nested polymerase chain reaction. HPV
      antibodies were tested using multiplex HPV serology. Kappa statistics and the
      Wilcoxon test were used to assess concordance, and regression analysis was used
      to calculate ORs and 95% CIs. RESULTS: HPV DNA was detected in 17.9% of oral
      samples from newborns and in 16.4% of the cervical samples of the mothers. At
      delivery, mother-newborn pairs had similar HPV-genotype profiles, but this
      concordance disappeared in 2 months. Oral HPV carriage in newborns was most
      significantly associated with the detection of HPV in the placenta (OR=14.0; 95%
      CI, 3.7-52.2; P=.0001). The association between status of the cord blood and oral
      HPV was also significant at delivery (OR=4.7; 95% CI, 1.4-15.9; P=.015) but
      disappeared within 1 month. HPV antibodies in infants were of maternal origin
      (OR=68; 95% CI, 20.1-230.9; P=.0001). CONCLUSIONS: HPV is prevalent in oral
      samples from newborns. The genotype profile of newborns was more restricted than
      that of the maternal cervical samples. The close maternal-newborn concordance
      could indicate that an infected mother transmits HPV to her newborn via the
      placenta or cord blood.

PMID- 22137369
TI  - Development of immunosensors for direct detection of three wound infection
      biomarkers at point of care using electrochemical impedance spectroscopy.
AB  - A method for label-free, electrochemical impedance immunosensing for the
      detection and quantification of three infection biomarkers in both buffer and
      directly in the defined model matrix of mock wound fluid is demonstrated.
      Triggering Receptor-1 Expressed on Myeloid cells (TREM-1) and Matrix
      MetalloPeptidase 9 (MMP-9) are detected via direct assay and N-3-oxo-dodecanoyl-l
      HomoSerineLactone (HSL), relevant in bacterial quorum sensing, is detected using
      a competition assay. Detection is performed with gold screen-printed electrodes
      modified with a specific thiolated antibody. Detection is achieved in less than
      1h straight from mock wound fluid without any extensive sample preparation steps.
      The limits of detection of 3.3 pM for TREM-1, 1.1 nM for MMP-9 and 1.4 nM for HSL
      are either near or below the threshold required to indicate infection. A
      relatively large dynamic range for sensor response is also found, consistent with
      interaction between neighbouring antibody-antigen complexes in the close-packed
      surface layer. Together, these three novel electrochemical immunosensors
      demonstrate viable multi-parameter sensing with the required sensitivity for
      rapid wound infection detection directly from a clinically relevant specimen.

PMID- 22137370
TI  - [Susceptibility to measles and varicella in healthcare workers in a tertiary
      hospital in Catalonia].
AB  - INTRODUCTION: To estimate the susceptibility to measles and varicella
      (chickenpox) in healthcare workers in a public tertiary level teaching hospital,
      in Catalonia. METHODS: A prevalence study was conducted from January 2006 to
      December 2008 on 2,752 workers who had serology performed for the determination
      of measles or varicella by ELISA test during a health examination. Data were
      analysed by, sex, age, professional category and work unit. RESULTS: A total of
      153 healthcare workers were susceptible to measles and 187 to varicella. The
      susceptibility of healthcare workers to measles was 6.04% (95% CI: 5.78 to 6.30),
      and to varicella it was 7.45% (95% CI: 7.14 to 7.75). The highest susceptibility
      to measles was in resident physicians with 14% (95% CI: 10.8 to 18.5). In high
      risk services, where highly immunocompromised patients are attended, the
      susceptibility of workers was slightly higher than the rest to measles (6.32% vs
      5.93%) and varicella (8.34% vs 7.09%). Healthcare workers born after 1980 were 20
      times (95% CI: 11.0 to 37.2) more likely to be susceptible to measles, and 2
      times (95% CI: 1.2 to 3.2) more likely to be susceptible to varicella than those
      those born before 1965. CONCLUSIONS: The susceptibility to measles in healthcare
      workers in our centre is higher in younger cohorts, with values higher than
      expected in a community with high vaccination coverage against measles, mumps,
      rubella vaccine (MMR) in the paediatric population for many years.

PMID- 22137371
TI  - [Iliopsoas abscess: therapeutic approach and outcome in a series of 35 patients].
AB  - INTRODUCTION: The present study was aimed at reviewing the iliopsoas abscess
      (IPA) from a contemporary perspective, on the basis of experience from two
      tertiary referral centres. MATERIAL AND METHODS: We performed a retrospective
      analysis of 35 cases of IPA diagnosed between 1998 and 2009. Their clinical and
      microbiological features were recorded, as well as their long-term outcome
      according to the type of treatment: antibiotics alone (10 patients), or
      antibiotics plus percutaneous drainage or surgery (25 patients). RESULTS: Primary
      abscess occurred in 8 patients. The most frequent source of secondary abscesses
      was spondylodiscitis. The classic clinical triad (fever, pain and functional
      impairment) was present in 10 patients, with a median duration of symptoms before
      diagnosis of 12 days. Staphylococcus aureus was the most frequently isolated
      microorganism. At the end of a median follow-up of 454 days, the risk of poor
      outcome (related death and/or relapse) was higher among patients with diabetes
      mellitus (44.4% vs. 7.7%; P=.027), with no significant differences according to
      the therapeutic approach (20.0% in the group of antibiotics alone vs. 28.0% in
      the group with drainage or surgery). CONCLUSIONS: In our series, most cases of
      IPA were due to S. aureus and secondary to a skeletal source. Antibiotic therapy
      seems effective in the long-term, although diabetic patients had a higher risk of
      relapse.

PMID- 22137372
TI  - [Introduction of a rapid HIV test in Sexually Transmitted Infections Units].
AB  - INTRODUCTION: The aim of the study was to analyze the implementation of a rapid
      HIV test in Asturias (Spain). METHODS: The study was conducted in two STI Units
      using the Determine(r) HIV-1/2 test. RESULTS: A total of 1011 people were tested,
      of whom 65.3% had never been tested for HIV previously, and 71.4% were
      heterosexual men. Twenty-one tests were confirmed positive by Enzyme
      Immunoassay/Western Blot (EIA/WB) assay An increase was observed in the diagnosis
      of HIV. CONCLUSION: Awareness campaigns and rapid tests could be effective
      methods for the early diagnosis of HIV.

PMID- 22137373
TI  - Special issue on mast cells in inflammation.

PMID- 22137375
TI  - Feasibility of contralateral trapezius transfer to restore shoulder external
      rotation: part I.
AB  - PURPOSE: We evaluated the feasibility of contralateral trapezius transfer to
      restore shoulder external rotation. MATERIALS AND METHODS: The length of the
      lower trapezius and distance necessary for contralateral trapezius transfer were
      measured in 20 volunteers and directly in 12 cadavers. The average distances
      between the medial spine of the scapula and T12 (length of lower trapezius) and
      the spine to the greater tuberosity (distance for transfer) were measured with
      the scapula neutral, maximally protracted, and maximally retracted. In cadavers,
      the origin of the lower trapezius was detached, transferred to the contralateral
      greater tuberosity, and retracted to determine its effectiveness in external
      rotation and tension on the vascular pedicle. RESULTS: In volunteers, the average
      difference between the length of the lower trapezius and the transfer distance
      was 19 mm in neutral. When the scapula was protracted and retracted, the
      difference was 79 and -49 mm. In the cadavers, the average transfer distance (in
      mm) was 290 +/- 12, 365 +/- 15, and 209 +/- 25 in the neutral, protracted, and
      retracted positions, respectively. The average length of the lower trapezius (in
      mm) was 270 +/- 10, 285 +/- 12, and 258 +/- 10 in the neutral, protracted, and
      retracted positions. The transfer was universally feasible when the scapula was
      partially retracted. Prolongation of the lower trapezius with lumbar fascia made
      the transfer possible in all scapular positions. Pulling on the transferred
      muscle resulted in contralateral shoulder external rotation without tension or
      impingement on the neurovascular pedicle. CONCLUSION: Contralateral trapezius
      transfer to the infraspinatus insertion appears feasible and potentially
      effective in restoration of shoulder external rotation.

PMID- 22137374
TI  - Development of a foot scanner for assessing the mechanical properties of plantar
      soft tissues under different bodyweight loading in standing.
AB  - Mechanical properties of plantar soft tissues are important characteristics of
      the foot and are prone to being affected by foot pathologies such as diabetes.
      Therefore, it is of great importance to measure the mechanical properties of
      plantar soft tissues in vivo. However, such measurement in previous studies is
      mostly conducted in foot without loading and there is a paucity of instrument
      available which can assess the foot mechanical properties under a weight-loading
      status. In this study, a foot scanner incorporating a tissue ultrasound palpation
      (indentation) system (TUPS) which could assess the mechanical properties of
      plantar soft tissues under different body-weight loading was developed. The
      movement of the foot could also be monitored in real time during the indentation
      test to improve the test reliability. Preliminary tests were conducted on ten
      normal subjects at the heel region under various loading of the bodyweight. The
      results showed that the thickness decreased by 12.0% (from 13.83+/-2.52 mm to
      12.10+/-1.95 mm) while the stiffness increased by 83.4% (from 40.0+/-20.7 kPa to
      69.0+/-26.0 kPa) when the loading increased from 0% to 80% of the bodyweight
      (both p<0.001, repeated measure one-way ANOVA). Therefore, our system has been
      demonstrated to be useful in studying the loading dependence of mechanical
      properties of plantar soft tissues. Potential applications of the system in
      clinical studies for characterization and monitoring of foot pathologies such as
      ageing and diabetes are discussed at the end of this note.

PMID- 22137376
TI  - A quantitative three-dimensional templating method for shoulder arthroplasty:
      biomechanical validation in cadavers.
AB  - BACKGROUND: Press-fit humeral components for total shoulder arthroplasty have
      notable potential complications that may be minimized by preoperative templating
      and improvements in stem design. The purpose of this study was to develop a 3
      dimensional templating technique for the humeral stem and to validate this
      templating in cadaveric specimens. MATERIALS AND METHODS: A cylindrical stem and
      a stem with a rectangular cross-section were selected for templating and force
      measurements. Templating was carried out for 15 clinical patients and 16
      cadaveric shoulders, including calculation of the cortical-implant volume ratio
      (CIVR). Insertion forces for stem broaching and impaction were measured for 15
      patients and 8 paired cadaveric shoulders. Hoop strain and periprosthetic
      fractures were monitored in cadaveric shoulders with strain gauges. RESULTS: A
      significant difference in the CIVR was noted between rectangular and cylindrical
      stems. No difference was observed in impact forces for ideally sized rectangular
      or cylindrical stems. A difference in insertion forces was found between
      oversized cylindrical and oversized rectangular implant stems and also between
      ideal and oversized cylindrical implant stems. The difference in maximal hoop
      strain between ideally sized rectangular and cylindrical stems was also
      statistically significant. CONCLUSIONS: CIVR is useful to predict an ideal
      humeral stem size. Cylindrical stems have a different design rationale for
      fixation than rectangular stems. Surgeon awareness of the fixation rationale for
      a particular stem design is important because different stem types have different
      effects on the insertion force. More anatomic humeral stem designs may help to
      minimize the risk of complications and optimize stem fixation.

PMID- 22137377
TI  - Prognostic value of extravascular lung water index in critically ill patients: a
      systematic review of the literature.
AB  - BACKGROUND: The prognostic value of extravascular lung water (EVLW) has been
      widely investigated; however, a wide range of its predictive accuracy has been
      reported. STUDY DESIGN: A meta-analysis of diagnostic test studies was conducted.
      SETTING AND POPULATION: Various patient populations in the intensive care unit
      were included, such as burned patients and patients with acute lung injury/acute
      respiratory distress syndrome and sepsis. SELECTION CRITERIA: A computerized
      search of PubMed, Current Contents, CINAHL, and EMBASE from inception until March
      1, 2011, was performed to identify potentially relevant articles. The inclusion
      criteria were studies investigating the prognostic value of EVLW in critically
      ill patients. There was no language restriction in the searching. INDEX TESTS:
      The EVLW index (EVLWI) was used. REFERENCE TESTS: The outcome was mortality
      (including in-hospital mortality, intensive care unit mortality, and 28-day
      mortality). RESULTS: We analyzed data from 11 studies and 9 countries involving
      670 patients. Overall, the EVLWI was significantly higher in nonsurvivors than in
      survivors, with a mean difference of 5.06 mL/kg (95% confidence interval, -7.53
      to -2.58). The heterogeneity was significant with I(2) = 90%. The pooled
      statistics of diagnostic accuracy together with relevant 95% confidence interval
      were as follows: sensitivity, 0.81 (0.72-0.88); specificity, 0.66 (0.55-0.76);
      diagnostic odds ratio, 8.84 (3.83-20.4), positive likelihood ratio, 2.44 (1.69
      3.52); negative likelihood ratio, 0.28 (0.16-0.46). LIMITATIONS: The sample sizes
      of included studies were small. CONCLUSION: The EVLWI appears to be a good
      predictor of mortality in critically ill patients.

PMID- 22137378
TI  - The adequacy of timely empiric antibiotic therapy for ventilator-associated
      pneumonia: an important determinant of outcome.
AB  - OBJECTIVE: The individual impact of timeliness vs adequacy of empiric antibiotic
      therapy for a clinical suspicion of ventilator-associated pneumonia (CSVAP) is
      unknown. Accordingly, in patients with CSVAP and timely initiation of empiric
      antibiotic therapy, we determined the impact of inadequate therapy (IT). METHODS:
      Analysis of a randomized trial of CSVAP treated empirically with meropenem or
      meropenem plus ciprofloxacin was done. Adequate therapy (AT) was considered
      present if all pathogens in the index culture were sensitive to the empiric
      antibiotics; IT was defined as the presence of pathogens resistant to the empiric
      antibiotics. A priori, for Pseudomonas sp, 2 antibiotics with activity against
      the organisms were required for AT to be considered present. RESULTS: Of 739
      patients with CSVAP, 350 had positive cultures: 313 (89.4%) had AT, and 37
      (10.6%), IT. The IT group had higher intensive care unit (35.1% vs 11.8%, P =
      .0001) and hospital mortalities (48.7% vs 19.5%, P < .0001), increased mechanical
      ventilation (15.8 vs 6.8 days, P = .0005), intensive care unit stay (13.5 vs 8.4
      days, P = .02), and hospital stay (42.2 vs 27.9 days, P = .04). In multivariate
      analysis and a separate case control analysis, the odds ratio of hospital
      mortality with IT was 3.05 (95% confidence interval, 1.25-7.45; P = .01) and 3.00
      (95% confidence interval, 1.24-7.24; P = .01), respectively. CONCLUSION: In the
      context of early administration of empiric broad spectrum antibiotics for CSVAP,
      IT is associated with higher morbidity and mortality.

PMID- 22137379
TI  - The sensitivity and specificity of ultrasound estimation of central venous
      pressure using the internal jugular vein.
AB  - PURPOSE: The fluid volume status of a patient is difficult to assess clinically.
      The aim of this study was to compare the ultrasound estimation of the height of
      the right internal jugular vein (CVP(IJV)) with direct estimation of central
      venous pressure (CVP) (CVP(CVC)). MATERIALS AND METHODS: A portable ultrasound
      machine defined the "top" of the right internal jugular vein in 44 patients from
      a single tertiary hospital. The vertical height from this point to the sternal
      angle was used to estimate CVP(IJV). A central venous catheter was then inserted
      and direct measurement of CVP was made with a pressure transducer. A normal CVP
      was defined as 3 to 6 mm Hg. RESULTS: For overloaded patients, CVP(IJV)
      correlated well with CVP(CVC), P = .004, sensitivity of 64.3%, specificity of
      81.3%, and positive predictive value of 85.7%. The area under the curve for the
      receiver operating characteristic curve was 0.73 (95% confidence interval, 0.59
      0.86). For undervolumed patients, the correlation remained statistically
      significant, P < .001, sensitivity of 88.9%, specificity of 77.1%, and negative
      predictive value of 96.4%. The area under the curve was 0.83 (95% confidence
      interval, 0.70-0.96). CONCLUSION: Ultrasound estimation of CVP using a portable
      ultrasound machine and the internal jugular vein is simple, noninvasive, and
      accurate.

PMID- 22137380
TI  - Multifocal fibrosclerosis and IgG4-related disease involving the cardiovascular
      system.
AB  - The cardiovascular system may be involved as a target organ of multifocal
      fibrosclerosis, which may manifest as idiopathic retroperitoneal fibrosis,
      inflammatory aortic aneurysm, inflammatory periarteritis, and inflammatory
      pericarditis. These pathological conditions can sometimes occur concomitantly.
      Idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm
      are both characterized by the presence of fibro-inflammatory tissue around the
      abdominal aorta expanding into the surrounding retroperitoneal structures, and
      together they may be termed 'chronic periaortitis'. Cardiovascular fibrosclerosis
      has become non-uncommonly encountered condition since imaging modalities have
      made its diagnosis more feasible. In addition, recent studies have demonstrated
      that a certain fraction, but not all, of cardiovascular fibrosclerosis may have a
      link with immunoglobulin-G4 (IgG4)-related sclerosing disease (IgG4-SD). IgG4-SD
      is histologically characterized by dense fibrosclerosis and infiltration of
      lymphocytes and IgG4-positive plasma cells, and these histopathologic findings
      seem to be essentially similar regardless of the organs involved. In this mini
      review, we summarize what is known so far about multifocal fibrosclerosis of the
      cardiovascular system and its association with IgG4-SD, and what remains to be
      clarified in future investigations.

PMID- 22137382
TI  - General practice: struggling to deliver.

PMID- 22137383
TI  - New approaches to dealing with opioid drug dependence.

PMID- 22137384
TI  - Fair and equal assessment in postgraduate training? A future research agenda.

PMID- 22137385
TI  - Survivors of critical illness: victims of our success?

PMID- 22137387
TI  - GP continuing professional development--done and dusted?

PMID- 22137386
TI  - RCGP Annual Conference.

PMID- 22137388
TI  - The QOF, NICE, and depression.

PMID- 22137389
TI  - The increase in spend.

PMID- 22137390
TI  - Ubi Scientia in the midst of the cosy cardigans of Caritas.

PMID- 22137391
TI  - Primary care electronic health records: who is in control?

PMID- 22137392
TI  - Electronic health records: research into design and implementation.

PMID- 22137393
TI  - Alcohol and pregnancy.

PMID- 22137394
TI  - The Olympic legacy.

PMID- 22137395
TI  - Physical inactivity is associated with earlier mortality--the evidence is
      incontrovertible.

PMID- 22137396
TI  - Time for a national undergraduate curriculum for primary care.

PMID- 22137397
TI  - Time for a national undergraduate curriculum for primary care.

PMID- 22137398
TI  - Trainees and palliative care.

PMID- 22137399
TI  - Extent of cotton-bud use in ears.

PMID- 22137400
TI  - Nursing care in hospitals.

PMID- 22137401
TI  - Edward R Tufte--the 'Information Man': a profile of America's leading proponent
      of effective strategies for seeing and showing.

PMID- 22137402
TI  - A social institution based on mutuality and trust.

PMID- 22137403
TI  - A Jester joins The Gatekeeper and Wizard: working as an academic GP.

PMID- 22137404
TI  - Registrar to GP: a transition.

PMID- 22137406
TI  - Let's reflect: what is the point?

PMID- 22137410
TI  - What do we actually know about the referral process?

PMID- 22137411
TI  - Harmful drinking and alcohol dependence: advice from recent NICE guidelines.

PMID- 22137412
TI  - Tips for GP trainees working in general medicine.

PMID- 22137413
TI  - Comparison of methadone and buprenorphine for opiate detoxification (LEEDS
      trial): a randomised controlled trial.
AB  - BACKGROUND: Many opiate users require prescribed medication to help them achieve
      abstinence, commonly taking the form of a detoxification regime. In UK prisons,
      drug users are nearly universally treated for their opiate use by primary care
      clinicians, and once released access  GP services where 40% of practices now
      treat drug users. There is a paucity of evidence evaluating methadone and
      buprenorphine (the two most commonly prescribed agents in the UK) for opiate
      detoxification. AIM: To evaluate whether buprenorphine or methadone help to
      achieve  drug abstinence at completion of a reducing regimen for heroin users
      presenting to UK prison health care for detoxification. DESIGN: Open-label,
      pragmatic, randomised controlled trial in three prison primary healthcare
      departments in the north of England. METHOD: Prisoners (n = 306) using illicit
      opiates were recruited and given daily sublingual buprenorphine or oral
      methadone, in the context of routine care, over a standard reduced regimen of not
      more than 20 days. The primary outcome measure was abstinence from illicit
      opiates at 8 days post  detoxification, as indicated by urine test (self
      report/clinical notes where urine sample was not feasible). Secondary outcomes
      were also recorded. RESULTS: Abstinence was ascertained for 73.7% at 8 days post
      detoxification (urine sample = 52.6%, self report = 15.2%, clinical  notes =
      5.9%). There was no statistically significant difference in the odds of achieving
      abstinence between methadone and buprenorphine (odds ratio [OR] = 1.69; 95%
      confidence interval [CI] = 0.81 to 3.51; P = 0.163). Abstinence was associated
      solely with whether or not the participant was  still in prison at that time
      (15.22 times the odds; 95% CI = 4.19 to 55.28). The strongest association for
      lasting abstinence was abstinence at an earlier time point. CONCLUSION: There is
      equal clinical effectiveness between methadone and buprenorphine in achieving
      abstinence  from opiates at 8 days post detoxification within prison.

PMID- 22137415
TI  - Primary care access and its relationship with emergency department utilisation:
      an observational, cross-sectional, ecological study.
AB  - BACKGROUND: Recent health service policies in the UK have focused on improving
      primary care access in order to reduce the use of costly emergency department
      services, even though the relationship between the two is based on weak or little
      evidence. Research is required to  establish whether improving primary care
      access can influence emergency department attendance. AIM: To ascertain whether a
      relationship exists between the degree of access to GP practices and avoidable
      emergency department attendances in an inner-London primary care trust  (PCT).
      DESIGN AND SETTING: Observational, cross-sectional ecological study in 68 general
      practices in Brent Primary Care Trust, north London, UK. METHOD: GP practices
      were used as the unit of analysis and avoidable emergency department attendance
      as the  dependent variable. Routinely collected data from GP practices, Hospital
      Episode Statistics, and census data for the period covering 2007-2009 were used
      across three broad domains: GP access characteristics, population
      characteristics, and health status aggregated to the level of the  GP practice.
      Multiple linear regression was used to ascertain which variables account for the
      variation in emergency department attendance experienced by patients registered
      to each GP practice. RESULTS: None of the GP access variables accounted for the
      variation in emergency  department attendance. The only variable that explained
      this variance was the Index of Multiple Deprivation (IMD). For every unit
      increase in IMD score of the GP practice, there would be an increase of 6.13 (95%
      CI = 4.56, 7.70) per 1000 patients per year in emergency department attendances. 
      This accounted for 47.9% of the variance in emergency department attendances in
      Brent. CONCLUSION: Avoidable emergency department attendance appears to be mostly
      driven by underlying deprivation rather than by the degree of access to primary
      care.

PMID- 22137414
TI  - Deep vein thromboses in users of opioid drugs: incidence, prevalence, and risk
      factors.
AB  - BACKGROUND: Users of illicit opioids are at increased risk of hospital admission
      for deep vein thromboses (DVTs); however, the community prevalence, risk factors,
      and complications of DVTs in this group are poorly understood. AIM: This study
      aimed to describe  the prevalence of previous DVT for users of opioids in primary
      care; provide age- and sex-adjusted annual incidence rates of DVT; and explore
      factors associated with DVT, concordance with subsequent treatment, and
      complications. DESIGN: A retrospective analysis of DVT prevalence  and incidence,
      and analysis of risk factors for DVT using Poisson regression of incidence rates.
      METHOD: A review of 734 patients in treatment for opioid addiction, who were
      registered to a single, specialised primary care practice in Middlesbrough,
      England. RESULTS: The prevalence of previous DVT in users of opioids was 13.9%
      (95% confidence interval [CI] = 11.5 to 16.6) with an annual incidence rate of
      3.2% (95% CI = 2.6 to 3.7). The incidence rate increased with age and for female
      users; an exploration of risk factors suggests that rising age, female  sex, sex
      worker status, and intravenous delivery all independently increase the risk of
      DVT. Concordance with treatment appeared reasonable and, compared with DVT in
      groups of people who do not use drugs, there was no evidence of increased risk of
      pulmonary embolism. Participants with previous  DVT reported lower health and
      wellbeing scores. CONCLUSION: Primary care providers should be aware of the
      considerably increased risk of DVT and its sequelae in users of intravenous
      drugs. Evidence for effective primary care prevention and the effective
      management of DVT  complications is lacking; until this emerges, vigilance on the
      part of clinicians may help to minimise harm.

PMID- 22137416
TI  - Fit for purpose? Using the fit note with patients with chronic pain: a
      qualitative study.
AB  - BACKGROUND: Staying in work may benefit patients with chronic pain, but can be
      difficult for GPs to negotiate with patients and their employers. The new fit
      note is designed to help this process, but little is known of how it is
      operating. AIM: To explore  GPs' views on the fit note, with particular reference
      to sickness certification for patients with chronic pain. DESIGN AND SETTING:
      Qualitative study using semi-structured interviews in eight primary care trusts
      in south-west England. METHOD: In-depth  interviews with 13 GPs. RESULTS: GPs
      reported that the rationale behind the fit note is sound and that it may help
      patients with chronic pain to return to work earlier. However, GPs also reported
      barriers to successful fit note use, including the need to preserve doctor
      patient  relationships, inconsistent engagement from employers, GPs' lack of
      specialist occupational health knowledge, issues with fit note training, and
      whether a new form can achieve cultural shift. CONCLUSION: While doctors agree
      that good work improves health outcomes, they do  not think that fit notes will
      greatly alter sickness-certification rates without more concerted initiatives to
      manage the tripartite negotiation between doctor, patient, and employer.

PMID- 22137417
TI  - Does higher quality primary health care reduce stroke admissions? A national
      cross-sectional study.
AB  - BACKGROUND: Hospital admission rates for stroke are strongly associated with
      population factors. The supply and quality of primary care services may also
      affect admission rates, but there is little previous research. AIM: To determine
      if the hospital admission rate for stroke is reduced by effective primary and
      secondary prevention in primary care. DESIGN AND SETTING: National cross
      sectional study in an English population (52,763,586 patients registered with
      7969 general practices in 152 primary care trusts). METHOD: A combination of data
      on hospital admissions for 2006-2009, primary healthcare staffing, practice
      clinical quality and access indicators, census sources, and prevalence estimates
      was used. The main outcome measure was indirectly standardised hospital admission
      rates for stroke, for each practice population. RESULTS: Mean (3 years) annual
      stroke admission rates per 100,000 population varied from zero to 476.5 at
      practice level. In a practice-level multivariable Poisson regression, observed
      stroke prevalence, deprivation, smoking prevalence, and GPs/100,000 population
      were all risk factors for hospital admission. Protective healthcare factors
      included the percentage of stroke or transient ischaemic attack patients whose
      last measured total cholesterol was <=5 mmol/l (P<0.001), and ability to book an
      appointment with a GP (P<0.003). All effect sizes were relatively small.
      CONCLUSION: Associations of stroke admission rates with deprivation and smoking
      highlight the need for smoking-cessation services. Of the stroke and hypertension
      clinical quality indicators examined, only reaching a total cholesterol target
      was associated with reduced admission rates. Patient experience of access to
      primary care may also be clinically important. In countries with well-developed
      primary healthcare systems, the potential to reduce hospital admissions by
      further improving the clinical quality of primary healthcare may be limited.

PMID- 22137419
TI  - Interventions to reduce primary care delay in cancer referral: a systematic
      review.
AB  - BACKGROUND: Reducing delay in the primary care part of the cancer care pathway is
      likely to improve cancer survival. Identifying effective interventions in primary
      care would allow action by primary healthcare professionals and local
      commissioners to reduce delay. AIM: To identify interventions that reduce primary
      care delay in the referral of patients with cancer to secondary care. DESIGN AND
      SETTING: Systematic review in primary care. METHOD: Eight electronic databases
      were searched using terms for primary  care, cancer, and delay. Exclusion
      criteria included screening and the 2-week-wait referral system. Reference lists
      of relevant papers were hand searched. The quality of each paper was assessed
      using predefined criteria, and checked by a second reviewer. RESULTS: Searches 
      identified 1798 references, of which 22 papers were found to meet the criteria.
      Interventions concerning education, audit and feedback, decision support software
      and guideline use, diagnostic tools, and other specific skills training were
      identified. Most studies reported a positive effect  on their specified outcomes,
      although no study measured a direct effect on reducing delay. CONCLUSION: There
      was no evidence that any intervention directly reduced primary care delay in the
      diagnosis of cancer. Limited evidence suggests that complex interventions,
      including  audit and feedback and specific skills training, have the potential to
      do so.

PMID- 22137420
TI  - Medicalisation, morality, and addiction: why we should be wary of problem
      gamblers in primary care.

PMID- 22137418
TI  - Case identification of depression in patients with chronic physical health
      problems: a diagnostic accuracy meta-analysis of 113 studies.
AB  - BACKGROUND: Depression is more likely in patients with chronic physical illness,
      and is associated with increased rates of disability and mortality. Effective
      treatment of depression may reduce morbidity and mortality. The use of two stem
      questions for case finding in diabetes and coronary heart disease is advocated in
      the Quality and Outcomes Framework, and has become normalised into primary care.
      AIM: To define the most effective tool for use in consultations to detect
      depression in people with chronic physical illness. DESIGN: Meta-analysis.
      METHOD: The following data sources were searched: CENTRAL, CINAHL, Embase, HMIC,
      MEDLINE, PsycINFO, Web of Knowledge, from inception to July 2009. Three authors
      selected studies that examined identification tools and used an interview-based
      ICD (International Classification of Diseases) or DSM (Diagnostic and statistical
      Manual of Mental Disorders) diagnosis of depression as reference standard. At
      least two authors independently extracted study characteristics and outcome data
      and assessed methodological quality. RESULTS: A total of 113 studies met the
      eligibility criteria, providing data on 20,826 participants. It was found that
      two stem questions, PHQ-9 (Patient Health Questionnaire), the Zung, and GHQ-28
      (General Health Questionnaire) were the optimal measures for case identification,
      but no method was sufficiently accurate to recommend as a definitive case-finding
      tool. Limitations were the moderate-to-high heterogeneity for most scales and the
      facts that few studies used ICD diagnoses as the reference standard, and that a
      variety of methods were used to determine DSM diagnoses. CONCLUSION: Assessing
      both validity and ease of use, the two stem questions are the preferred method.
      However, clinicians should not rely on the two-questions approach alone, but
      should be confident to engage in a more detailed clinical assessment of patients
      who score positively.

PMID- 22137421
TI  - The importance of identifying the association between metabolic alkalosis and
      respiratory acidosis.

PMID- 22137422
TI  - The insertion of self expanding metal stents with flexible bronchoscopy under
      sedation for malignant tracheobronchial stenosis: a single-center retrospective
      analysis.
AB  - OBJECTIVE: To describe a 10-year experience of inserting UltraflexTM self
      expanding metal stents (SEMS) under sedation using flexible bronchoscopy for the
      treatment of malignant tracheobronchial stenosis in a tertiary referral centre.
      METHODS: Medical notes were retrospectively reviewed for all patients who
      underwent SEMS insertion between 1999 and 2009. RESULTS: A data analysis of 68
      patients who had UltraflexTM SEMS inserted under sedation was completed. Thirty
      three males and 35 females with a mean age of 67.9 years (range 35-94) presented
      with features including dyspnea/respiratory distress (39 patients), stridor (16
      patients) and hemoptysis/dyspnea (13 patients). Etiology of stenosis included
      lung cancer (46 patients) esophageal cancer (14 patients) and other malignancies
      (8 patients). Mean dose of midazolam administered was 5mg (range 0-10mg). The
      trachea was the most common site of stent insertion followed by the right and
      left main bronchus, respectively. Adjuvant laser therapy was applied at some
      stage in 31% of all cases, and chemotherapy and/or radiotherapy was administered
      to at least 64% of patients with malignant disease. Hemoptysis and stent
      migration were the most frequent complications (5 and 4 patients, respectively).
      The mean survival time of stented non-small cell lung cancer (NSCLC) patients was
      214 days (range 5-1233) and that of esophageal malignancy was 70 days (range 12
      249). Mean pack-year history of individuals with lung cancer requiring stent
      insertion was 37 (range 2-100). CONCLUSION: Ultraflex stents offer a safe and
      effective therapy for patients who are inoperable or unresectable that otherwise
      would have no alternative therapy. It has an immediate beneficial effect upon
      patients, not only through symptom relief but, in some, through prolongation of
      life. Survival data is no worse than other studies using different varieties of
      stents and insertion techniques indicating its longer-term efficacy. Moreover,
      this report highlights the feasibility of performing this procedure successfully
      in a respiratory unit, without the need for general anesthesia.

PMID- 22137423
TI  - Gastric schwannoma: a clinicopathologic study of 51 cases and critical review of
      the literature.
AB  - Schwannoma is a rare gastrointestinal mesenchymal tumor, as the vast majority of
      gastric mesenchymal tumors are gastrointestinal stromal tumors. In this study, we
      analyzed clinicopathologically 51 gastric schwannomas. These tumors predominantly
      occurred in older adults with a marked female predominance (40 women and 11 men;
      median and mean ages, 60 and 58 years). They variably presented with gastric
      discomfort, bleeding, or rarely gastric outlet obstruction; and many were
      incidental findings during other medical procedures. The tumors ranged from 1 to
      10.5 cm (median, 4.5 cm). The typical histologic features included spindle cells
      usually with microtrabecular architecture and focal nuclear atypia, and
      peritumoral lymphoid cuff, whereas features of soft tissue schwannomas, such as
      encapsulation, nuclear palisading, vascular hyalinization, and dilatation, were
      absent or infrequent. Median mitotic count was 2/50 high-power fields, with the
      highest count being 13/50 high-power fields. No malignant variants were
      recognized, and long-term follow-up did not reveal recurrences or metastases.
      Immunohistochemically, all examined tumors were S100 protein positive and most
      were also GFAP positive, whereas CD34 and NF68 were encountered rarely and all
      tumors were negative for HMB45, KIT, DOG1/Ano 1, smooth muscle actin, desmin, and
      synaptophysin. None of the 9 tumors studied contained gastrointestinal stromal
      tumor-specific KIT or PDGFRA mutations. Fluorescence in situ hybridization
      studies revealed multiple signals with BCR probe (chromosome 22) and centromeric
      probes for chromosomes 2 and 18 suggesting polyploidy. These findings indicate
      that gastric schwannoma is a distinctive form of peripheral nerve sheath tumor
      that in many ways differs from soft tissue schwannoma. It should be distinguished
      from gastrointestinal stromal tumor and other mesenchymal tumors of the
      gastrointestinal tract, such as the S100 protein-positive gastrointestinal clear
      cell sarcoma and metastatic melanoma.

PMID- 22137424
TI  - Denying a patient's final will: public safety vs. medical confidentiality and
      patient autonomy.
AB  - Especially when caring for patients approaching the end of life, physicians and
      nursing staff feel committed to fulfilling as many patient desires as possible.
      However, sometimes a patient's "final will" may threaten public safety. This can
      lead to severe conflicts, outweighing the physician's obligation and dedication
      to care for the patient and to respect his autonomy. Yet, public safety can be
      threatened if confidentiality is not broken. This article provides a concise
      summary of the medicolegal and ethical fundamentals concerning this difficult
      situation. If the patient's and others' health and safety are at risk, physicians
      may (and in some countries must) break medical confidentiality and disclose
      confidential patient information to the police and other authorities. Physicians
      should be able to professionally deal with such a conflict in all patients, not
      only in patients with advanced illness.

PMID- 22137425
TI  - Legislating for (public) health.

PMID- 22137426
TI  - Sleep breathing disorders in 40 Italian patients with Myotonic dystrophy type 1.
AB  - The aim of this study was to estimate the prevalence and nature of sleep
      breathing disorders in Myotonic dystrophy type 1 (DM1). We wanted to determine
      whether there is a relationship between sleep breathing disorders and clinical
      parameters such as pulmonary function, degree of neuromuscular impairment,
      daytime sleepiness, and fatigue. This will help assess the prevalence of DM1
      patients requiring nocturnal ventilatory treatments. We studied a random sample
      of 40 unrelated patients and found that 22/40 patients had obstructive sleep
      apnoea. Of these 22 patients, five showed also periodic breathing and four showed
      sleep hypoventilation. Nine patients were put on nocturnal ventilation following
      clinical and instrumental evaluations. Our study reveals that obstructive sleep
      apnoea is very common in these patients, but cannot be predicted on the basis of
      clinical-neurological features and diurnal functional respiratory tests. Our data
      emphasize that a periodical evaluation by polysomnography should be mandatory to
      ascertain, and treat if necessary, the presence of obstructive sleep apnoea,
      periodic breathing or nocturnal hypoventilation.

PMID- 22137427
TI  - Animal models of atherosclerosis.
AB  - Cardiovascular disease is currently the predominant cause of mortality worldwide
      and its incidence is expected to increase significantly during the next decades
      owing to the unhealthy effects of modern lifestyle habits (e.g., obesity and lack
      of physical exercise). Cardiovascular death is frequently associated with acute
      myocardial infarction or stroke, which are generally the ultimate consequence of
      an underlying atherosclerotic process. Small and big animal models are valuable
      tools to understand the molecular mechanisms underlying atherosclerotic plaque
      formation and progression, as well as the occurrence of associated ischemic
      events. Moreover, animal models of atherosclerosis are pivotal for testing
      mechanistic hypothesis and for translational research, including the assessment
      of dietary and/or pharmacological interventions and the development of imaging
      technologies and interventional devices. In this chapter, we will describe the
      most widely used animal models that have permitted major advances in
      atherosclerosis research and significant improvements in the treatment and
      diagnosis of atherosclerotic disease.

PMID- 22137429
TI  - Experimental models of seizures and epilepsies.
AB  - Epilepsy is one of the most common neurological conditions that affect people of
      all ages. Epilepsy is characterized by occurrence of spontaneous recurrent
      seizures. Currently available drugs are ineffective in controlling seizures in
      approximately one-third of patients with epilepsy. Moreover, these drugs are
      associated with adverse effects, and none of them are effective in preventing
      development of epilepsy following an insult or injury. To develop an effective
      therapeutic strategy that can interfere with the process of development of
      epilepsy (epileptogenesis), it is crucial to study the changes that occur in the
      brain after an injury and before epilepsy develops. It is not possible to
      determine these changes in human tissue for obvious ethical reasons. Over the
      years, experimental models of epilepsies have contributed immensely in improving
      our understanding of mechanism of epileptogenesis as well as of seizure
      generation. There are many models that replicate at least some of the
      characteristics of human epilepsy. Each model has its advantages and
      disadvantages, and the investigator should be aware of this before selecting a
      specific model for his/her studies. Availability of a good animal model is a key
      to the development of an effective treatment. Unfortunately, there are many
      epilepsy syndromes, specifically pediatric, which still lack a valid animal
      model. It is vital that more research is done to develop animal models for such
      syndromes.

PMID- 22137431
TI  - Acute phase proteins in animals.
AB  - Acute phase proteins (APP) were first identified in the early 1900s as early
      reactants to infectious disease. They are now understood to be an integral part
      of the acute phase response (APR) which is the cornerstone of innate immunity.
      APP have been shown to be valuable biomarkers as increases can occur with
      inflammation, infection, neoplasia, stress, and trauma. All animals--from fish to
      mammals--have demonstrable APP, but the type of major APP differs by species.
      While the primary application of these proteins in a clinical setting is
      prognostication, studies in animals have demonstrated relevance to diagnosis and
      detection and monitoring for subclinical disease. APP have been well documented
      in laboratory, companion, and large animals. With the advent of standardized and
      automated assays, these biomarkers are available for use in all fields of
      veterinary medicine as well as basic and clinical research.

PMID- 22137428
TI  - Genetic animal models of cerebral vasculopathies.
AB  - Cerebral amyloid angiopathy (CAA) and cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy (CADASIL) are genetic
      cerebrovasculopathies associated with neurodegeneration and vascular cognitive
      impairment. Linked to autosomal dominant mutations in diverse genes that encode
      cell-surface receptors (i.e., amyloid precursor protein in CAA and NOTCH3 in
      CADASIL), both diseases are associated with accumulation of abnormal material
      around cerebral vessels, such as amyloid in CAA or granular osmiophilic material
      in CADASIL. Both CAA and CADASIL share clinical features of white matter
      degeneration and infarcts, and vascular dementia in the human adult; microbleeds
      occur in both CADASIL and CAA, but large intracerebral hemorrhages are more
      characteristic for the latter. While the mechanisms are poorly understood, wall
      thickening, luminal narrowing, and eventual loss of vascular smooth muscle cells
      are overlapping pathologies involving leptomeningeal, and pial or penetrating
      small arteries and arterioles in CAA and CADASIL. Dysregulation of cerebral blood
      flow and eventual hypoperfusion are believed to be the key pathophysiological
      steps in neurodegeneration and cognitive impairment. Although animal models
      expressing CAA or CADASIL mutations have partially reproduced the human
      pathology, there has been marked heterogeneity in the phenotypic spectrum,
      possibly due to genetic background differences among mouse models, and obvious
      species differences between mouse and man. Here, we provide an overview of animal
      models of CAA and CADASIL and the insight on molecular and physiological
      mechanisms of disease gained from these models.

PMID- 22137433
TI  - Animal models of lung cancer characterization and use for chemoprevention
      research.
AB  - Of the potential sites of cancer development, cancer of the lung accounts for the
      highest number of cancer deaths each year in the United States (Jemal et al.,
      2010(1)). Based on its histopathological features, lung cancer is grouped into
      small cell lung cancer (SCLC; ~20%) and non-SCLC (NSCLC; ~80%), which is further
      divided into three subtypes: squamous cell carcinoma (~30%), adenocarcinoma
      (~50%), and large cell lung carcinoma. Every subtype of lung cancer has a
      relatively low 5-year survival rate that is attributed, in part, to the fact that
      they are routinely diagnosed at later histologic stages. Due to this alarming
      statistic, it is necessary to develop not only new and effective means of
      treatment but also of prevention. One of the promising approaches is
      chemoprevention which is the use of synthetic or natural agents to inhibit the
      initial development of or further progression of early lung lesions (Hong and
      Sporn, 1997). Many compounds have been identified as potentially effective
      chemopreventive agents using animal models. Most chemopreventive studies have
      been performed using mouse models which were developed to study lung adenomas or
      adenocarcinomas. More recently, models of squamous cell lung cancer and small
      cell lung cancer have also been developed. This review seeks to highlight mouse
      models which we helped to develop and presents the results of recent
      chemopreventive studies that we have performed in models of lung adenocarcinoma,
      squamous cell carcinoma, and small cell lung cancer.

PMID- 22137430
TI  - Animal models of muscular dystrophy.
AB  - The muscular dystrophies (MDs) represent a diverse collection of inherited human
      disorders, which affect to varying degrees skeletal, cardiac, and sometimes
      smooth muscle (Emery, 2002). To date, more than 50 different genes have been
      implicated as causing one or more types of MD (Bansal et al., 2003). In many
      cases, invaluable insights into disease mechanisms, structure and function of
      gene products, and approaches for therapeutic interventions have benefited from
      the study of animal models of the different MDs (Arnett et al., 2009). The large
      number of genes that are associated with MD and the tremendous number of animal
      models that have been developed preclude a complete discussion of each in the
      context of this review. However, we summarize here a number of the more commonly
      used models together with a mixture of different types of gene and MD, which
      serves to give a general overview of the value of animal models of MD for
      research and therapeutic development.

PMID- 22137434
TI  - Cardiovascular magnetic resonance imaging in small animals.
AB  - Noninvasive imaging studies involving small animals are becoming increasingly
      important in preclinical pharmacological, genetic, and biomedical cardiovascular
      research. Especially small animal magnetic resonance imaging (MRI) using high
      field and clinical MRI systems has gained significant importance in recent years.
      Compared to other imaging modalities, like computer tomography, MRI can provide
      an excellent soft tissue contrast, which enables the characterization of
      different kinds of tissues without the use of contrast agents. In addition,
      imaging can be performed with high spatial and temporal resolution. Small animal
      MRI cannot only provide anatomical information about the beating murine heart; it
      can also provide functional and molecular information, which makes it a unique
      imaging modality. Compared to clinical MRI examinations in humans, small animal
      MRI is associated with additional challenges. These included a smaller size of
      all cardiovascular structures and a up to ten times higher heart rate. Dedicated
      small animal monitoring devices make a reliable cardiac triggering and
      respiratory gating feasible. MRI in combination with molecular probes enables the
      noninvasive imaging of biological processes at a molecular level. Different kinds
      of iron oxide or gadolinium-based contrast agents can be used for this purpose.
      Compared to other molecular imaging modalities, like single photon emission
      computed tomography (SPECT) and positron emission tomography (PET), MRI can also
      provide imaging with high spatial resolution, which is of high importance for the
      assessment of the cardiovascular system. The sensitivity for detection of MRI
      contrast agents is however lower compared to sensitivity of radiation associated
      techniques like PET and SPECT. This chapter is divided into the following
      sections: (1) "Introduction," (2) "Principals of Magnetic Resonance Imaging," (3)
      "MRI Systems for Preclinical Imaging and Experimental Setup," and (4)
      "Cardiovascular Magnetic Resonance Imaging."

PMID- 22137435
TI  - Animal models of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition
      that is medicated by genetic, immune, and environmental factors. At least 66
      different kinds of animal models have been established to study IBD, which are
      classified primarily into chemically induced, cell-transfer, congenial mutant,
      and genetically engineered models. These IBD models have provided significant
      contributions to not only dissect the mechanism but also develop novel
      therapeutic strategies for IBD. In addition, recent advances on genetically
      engineered techniques such as cell-specific and inducible knockout as well as
      knockin mouse systems have brought novel concepts on IBD pathogenesis to the
      fore. Further, mouse models, which lack some IBD susceptibility genes, have
      suggested more complicated mechanism of IBD than previously predicted. This
      chapter summarizes the distinct feature of each murine IBD model and discusses
      the previous and current lessons from the IBD models.

PMID- 22137436
TI  - Animal models of molecular pathology systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple
      organ systems. A hallmark of SLE is the production of antinuclear antibodies
      against nuclear antigens such as chromatin and DNA. High levels of autoAbs
      promote the formation of immune complexes which can lead to the development of
      glomerulonephritis and progress to end-stage renal failure. Although the exact
      etiology of SLE is unknown, it is thought to be multifactorial in nature. A
      combination of environmental, hormonal, and a predisposed genetic background lead
      to the development of this disorder. Here, we review the various mouse models
      that have been used to study SLE and discuss how their study has led to a better
      understanding of the genetic and cellular factors involved in the development of
      systemic autoimmunity and lupus-like clinical symptoms. We also review the mouse
      studies that have explored the molecular pathways that are altered in this
      disease and the investigation of their therapeutic potentials.

PMID- 22137437
TI  - Animal models of cutaneous and hepatic fibrosis.
AB  - Fibrosis occurs as a part of normal wound healing. However, excessive or
      dysregulated fibrosis can lead to severe organ dysfunction and is a feature of a
      variety of diseases. Due to its insidious onset, fibrosis tends to go undetected
      in its early stages. This is in part why these diseases remain so poorly
      understood. Animal models have provided a means to examine these early stages and
      to isolate and understand the effect of perturbations in signaling pathways,
      chemokines, and cytokines. Here, we summarize recent progress in the
      understanding of the molecular pathogenesis of fibrosis, both its initiation and
      its maintenance phases, from animal models of fibrosis in the skin and liver. Due
      to these organs' properties, modeling fibrosis in them poses unique challenges.
      Elegant solutions have therefore been developed for modeling fibrosis in each,
      and now, great potential for animal models to contribute to our understanding
      appears scientifically imminent.

PMID- 22137438
TI  - Animal models of schizophrenia emphasizing construct validity.
AB  - Achieving animal models of schizophrenia which are representative of clear
      aspects of the illness is critical to understanding pathophysiology and
      developing novel treatments for the complex syndrome. This chapter reviews the
      various approaches that have been used in the past to create animal models of
      schizophrenia, including pharmacological approaches, environmental risk
      conditions and schizophrenia risk genes. In addition, we present a new animal
      model which derives directly from human tissue and brain imaging data used to
      develop a human schizophrenia model. This chapter emphasizes the crucial need for
      construct validity and of modeling discrete elements of schizophrenia's illness
      presentation as the way to successful advances.

PMID- 22137440
TI  - Descriptive analysis of malaria prophylaxis for travellers from Greece visiting
      malaria-endemic countries.
AB  - International travel is changing the epidemiology of imported malaria. Our aim
      was to study malaria prophylaxis administered to travellers from Greece. The
      study was conducted during 2008-2009. Data were collected using a standardized
      form. A total of 2337 travellers were studied; prophylaxis was recommended to
      60.2% of them. Of the 2337 travellers, 32.6% travelled to sub-Saharan Africa,
      25.5% to South America, 11.8% to Indian subcontinent, 11.7% to Middle East, and
      4.4% to Southeast Asia; prophylaxis was recommended to 77.4%, 64%, 80.6%, 4.8%
      and 73.5% of them, respectively. According to the purpose of travel, prophylaxis
      was recommended to 85.4% of those travelling for work, 75.2% of those visiting
      friends and relatives, and 62% of those travelling for recreation. Prophylaxis
      advised was provided to 68.5%, 66.2%, 61.5%, and 18.9% to those staying at a
      residence of local people, camping, hotels, and cruise ships, respectively.
      Regarding long-term travellers, malaria prophylaxis was recommended to 42.6%.
      Recommendation of malaria prophylaxis was significantly statistically in
      association with destination countries, purpose of travel, type of residence in
      endemic areas There is a need to improve recommendations for malaria prophylaxis
      for travellers from Greece, and to increase awareness and education of
      professionals providing travel health services in Greece.

PMID- 22137441
TI  - Plasmodium species co-infection as a cause of treatment failure.
AB  - We report a case of Plasmodium falciparum and Plasmodium malariae coinfection
      with associated failure of clinical response to artemether + lumefantrine
      therapy. This case highlights the need to consider co-infection in the setting of
      apparent treatment failure and the impact of mixed species infection upon host
      dynamics and clinical presentation. Recognition of malarial co-infection is
      clinically important for determining appropriate therapy and preventing disease
      sequelae.

PMID- 22137432
TI  - Animal models of hemophilia.
AB  - The X-linked bleeding disorder hemophilia is caused by mutations in coagulation
      factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic
      treatment is provided, patients with severe disease (less than 1% clotting
      activity) typically experience frequent spontaneous bleeds. Current treatment is
      largely based on intravenous infusion of recombinant or plasma-derived
      coagulation factor concentrate. More effective factor products are being
      developed. Moreover, gene therapies for sustained correction of hemophilia are
      showing much promise in preclinical studies and in clinical trials. These
      advances in molecular medicine heavily depend on availability of well
      characterized small and large animal models of hemophilia, primarily hemophilia
      mice and dogs. Experiments in these animals represent important early and
      intermediate steps of translational research aimed at development of better and
      safer treatments for hemophilia, such a protein and gene therapies or immune
      tolerance protocols. While murine models are excellent for studies of large
      groups of animals using genetically defined strains, canine models are important
      for testing scale-up and for long-term follow-up as well as for studies that
      require larger blood volumes.

PMID- 22137442
TI  - Burn and cancer risk: a state-wide longitudinal analysis.
AB  - BACKGROUND: Major burn can lead to impairment of the immune system and
      individuals who experience chronic immunosuppression are at a greater risk of
      developing a malignancy. Examination of prospective long term follow-up data to
      clarify the risk of cancer in this patient group is important. METHODS: Linked
      hospital morbidity records of 23,450 persons admitted with an index burn in
      Western Australia from 1983 to 2008 were merged with cancer and death data. The
      cancer incidence of those hospitalised for burn was compared to the general
      population of Western Australia. Poisson regression was used to assess the impact
      of burn severity and skin graft on cancer risk. RESULTS: From 1983 to 2008, there
      were 759 notifications of cancer (standardised incidence ratio (SIR), 95%
      confidence interval (CI): 0.97, 0.90-1.04). For the cohort admitted 1983-2008, a
      significant decrease in cancer risk for males (SIR, 95%CI: 0.90, 0.83-0.99), and
      a non-significant increase in cancer risk for females (SIR, 95%CI: 1.12, 1.00
      1.28) were estimated. For the sub-cohort admitted 1983-1987 with optimum follow
      up, incidence of cancer was significantly less for males (SIR, 95%CI: 0.86, 0.75
      0.99), while a significant increase in risk of cancer for females (SIR, 95%CI:
      1.39, 1.15-1.69) was estimated. CONCLUSIONS: There appears to be a gender effect
      in relation to incidence of cancer after burn. The risk of cancer for females
      hospitalised for burn during 1983-1987, with optimum follow-up time, was
      significant and increased in magnitude to 39% greater incidence of all-cause
      cancer than that for females in the general population of Western Australia. BURN
      AND CANCER RISK: A state-wide longitudinal analysis.

PMID- 22137443
TI  - Rulers of the zodiac.
AB  - Everybody thinks they know what science is, but pinning down a definite time and
      place for its origins is more problematic.

PMID- 22137444
TI  - Welfare states, flexible employment, and health: a critical review.
AB  - OBJECTIVES: The aim of this literature review is to identify whether differences
      between welfare regimes can manifest diverse consequences for the health effects
      of insecure and precarious employment, as well as to address challenging issues
      and implications for future research. METHODS: By searching PubMed, PsychINFO,
      Stork Social Science Citation Index, and Index Lilac, from 1988 to June 2010, a
      total of 104 original articles were selected (65 on job insecurity; 39 on
      precarious employment). RESULTS: After classifying selected empirical studies
      according to a six-regime welfare state typology (Scandinavian, Bismarckian,
      Southern European, Anglo-Saxon, Eastern European, and East Asian), this
      systematic review reveals that welfare regimes may be an important determinant of
      employment-related health. Precarious workers in Scandinavian welfare states
      report better or equal health status when compared to their permanent
      counterparts. By contrast, precarious work in the remaining welfare state regimes
      is found to be associated with adverse health outcomes, including poor self-rated
      health, musculoskeletal disorders, injuries, and mental health problems.
      CONCLUSIONS: Future research should be conducted by employing conceptual models
      that specify how macro-economic processes, country-level welfare factors, and
      individual employment histories and environments relate to employment-related
      health inequalities.

PMID- 22137445
TI  - Do we need broad immunological work-up in all patients with CIS?
AB  - BACKGROUND: The aim of this study was to determine the prevalence of altered
      immunological tests and their clinical significance in patients with clinically
      isolated syndrome (CIS) suggestive of multiple sclerosis (MS). PATIENTS AND
      METHODS: The information was gathered from medical records of patients
      hospitalized in the Referral Center for Demyelinating Diseases in the 2008-2010
      period. All patients had ANA, ENA profile, ANCA, aCl IgG and IgM, C3, C4, CH50,
      anti-TPO, AST and RF antibodies tested. RESULTS: From 726 patients with CIS that
      were reviewed, the complete battery of immunological tests was performed in 418
      of them (57.6%), representing our cohort. Altered tests were found in 235
      patients (56.2%); 73 (17.4%) had positive antinuclear antibodies, 14 (3.3%) had
      positive ENA, 47 (11.2%) had positive aCl IgG, 83 (19.8%) had positive aCl IgM,
      and 13 (3.1%) had anti TPO antibodies. We found no correlation between ANA, aCl
      IgG or IgM positivity (ANA vs aCL IgG p=0.554; ANA vs aCL IgM p=0.19; aCL IgG vs
      aCL IgM, p=0.155). None of the patients had any clinical manifestations other
      than MS symptoms. CONCLUSION: These results indicate that significant number of
      patients with CIS have altered immunological tests but nevertheless none of them
      had clinical expression of any other autoimmune disease making them clinically
      insignificant. In conclusion there is no need to perform extensive immunological
      work-up in all patients with CIS. Contrary, our results argue for more focused
      testing rather than a battery of screening tests.

PMID- 22137446
TI  - Melatonin dysregulation, sleep disturbances and fatigue in multiple sclerosis.
AB  - BACKGROUND: Sleep disruption and fatigue are common in Multiple Sclerosis (MS).
      Melatonin is one of the major regulators of sleep-wake cycle. The role of
      melatonin in MS-related sleep disturbances and fatigue as well as the interaction
      between melatonin and Interferon beta (IFN-beta) treatment were the subject of
      this study. OBJECTIVE: To assess the influence of IFN-beta treatment on melatonin
      secretion, fatigue and sleep characteristics in patients with MS. METHODS: 13 MS
      patients and 12 healthy controls participated. Fatigue was evaluated using the
      Fatigue Impact Scale (FIS), sleep was assessed by actigraphy and day/night levels
      of 6-sulphatoxy-melatonin (6-SMT) in urine were determined using a highly
      specific ELISA assay. RESULTS: Naive MS patients demonstrated significantly
      decreased levels of 6-SMT and disrupted circadian regulation of its secretion,
      which were increased with IFN-beta treatment, in association with improved
      fatigue. Sleep Efficiency was significantly lower in the MS group compared to
      controls. CONCLUSION: Our findings suggest dysregulation of Melatonin secretion
      in MS, which may be influenced by IFN-beta treatment. The results call for
      further characterization of the role of neuro-hormones such as melatonin in MS,
      and their cross-regulation with immune-mediators.

PMID- 22137447
TI  - Controlling toxic cyanobacteria: effects of dredging and phosphorus-binding clay
      on cyanobacteria and microcystins.
AB  - Sediment dredging and Phoslock((r)) addition were applied individually and in
      combination in an enclosure experiment in a Dutch hypertrophic urban pond. These
      measures were applied to control eutrophication and reduce the risk of exposure
      to cyanobacterial toxins. Over the 58 days course of the experiment,
      cyanobacteria (predominantly Microcystis aeruginosa) gradually decreased until
      they dropped below the level of detection in the combined treated enclosures,
      they were reduced in dredged enclosures, but remained flourishing in controls and
      Phoslock((r)) treated enclosures. Cyanobacteria were, however, less abundant in
      the enclosures (medians chlorophyll-a 30-87 MUg l(-1)) than in the pond (median
      chlorophyll-a 162 MUg l(-1)), where also a thick surface scum covered one-third
      of the pond for many weeks. Soluble reactive phosphorus (SRP), total phosphorus
      and total nitrogen concentrations were significantly lower in the combined
      dredged and Phoslock((r)) treated enclosures than in controls. Median SRP
      concentrations were 24 MUg P l(-1) in the combined treatment, 58 MUg P l(-1) in
      dredged enclosures, and 90 MUg P l(-1) in controls and 95 MUg P l(-1) in
      Phoslock((r)) treated enclosures. Hence, the combined treatment was most
      effective in decreasing SRP and TP, and in lowering cyanobacterial biomass.
      Microcystin (MC) concentrations were analyzed by LC-MS/MS. MC concentrations and
      cyanobacterial biomass were positively correlated in all treatments. Mean MC
      concentrations in controls (71 MUg l(-1)), Phoslock((r)) treated enclosures (37
      MUg l(-1)) and dredged enclosures (25 MUg l(-1)) exceeded the provisional
      guideline of 20 MUg l(-1), whereas mean MC concentrations were 13 MUg l(-1) in
      the combined treated enclosures. All samples contained the MC variants dmMC-RR,
      MC-RR, MC-YR, dmMC-LR and MC-LR; traces of MC-LY and nodularin were detected in
      few samples. The different treatments did not change the relative contribution of
      the variants to the MC pool; MC profiles in all treatments and the pond showed
      dominance of MC-RR followed by MC-LR. In the surface scum of the pond, total MC
      concentration was extremely high (64000 MUg l(-1) or 1300 MUg g(-1) DW), which
      poses a serious health hazard to children playing on the banks of the pond. Based
      on our results and pond characteristics, we propose combined sediment dredging
      and Phoslock((r)) addition, fish removal and strong reduction of duck feeding by
      the neighborhood as most promising measures controlling cyanobacterial hazards in
      this pond.

PMID- 22137448
TI  - A compartmental model to describe hydraulics in a full-scale waste stabilization
      pond.
AB  - The advancement of experimental and computational resources has facilitated the
      use of computational fluid dynamics (CFD) models as a predictive tool for mixing
      behaviour in full-scale waste stabilization pond systems. However, in view of
      combining hydraulic behaviour with a biokinetic process model, the computational
      load is still too high for practical use. This contribution presents a method
      that uses a validated CFD model with tracer experiments as a platform for the
      development of a simpler compartmental model (CM) to describe the hydraulics in a
      full-scale maturation pond (7 ha) of a waste stabilization ponds complex in
      Cuenca (Ecuador). 3D CFD models were validated with experimental data from pulse
      tracer experiments, showing a sufficient agreement. Based on the CFD model
      results, a number of compartments were selected considering the turbulence
      characteristics of the flow, the residence time distribution (RTD) curves and the
      dominant velocity component at different pond locations. The arrangement of
      compartments based on the introduction of recirculation flow rate between
      adjacent compartments, which in turn is dependent on the turbulence diffusion
      coefficient, is illustrated. Simulated RTD's from a systemic tanks-in-series
      (TIS) model and the developed CM were compared. The TIS was unable to capture the
      measured RTD, whereas the CM predicted convincingly the peaks and lags of the
      tracer experiment using only a minimal fraction of the computational demand of
      the CFD model. Finally, a biokinetic model was coupled to both approaches
      demonstrating the impact an insufficient hydraulic model can have on the outcome
      of a modelling exercise. TIS and CM showed drastic differences in the output
      loads implying that the CM approach is to be used when modelling the biological
      performance of the full-scale system.

PMID- 22137449
TI  - Cation exchange during subsurface iron removal.
AB  - Subsurface iron removal (SIR), or in-situ iron removal, is an established
      treatment technology to remove soluble iron (Fe(2+)) from groundwater. Besides
      the adsorptive-catalytic oxidation theory, it has also been proposed that the
      injection of O(2)-rich water onsets the exchange of adsorbed Fe(2+) with other
      cations, such as Ca(2+) and Na(+). In sand column experiments with synthetic and
      natural groundwater it was found that cation exchange (Na(+)-Fe(2+)) occurs
      during the injection-abstraction cycles of subsurface iron removal. The Fe(2+)
      exchange increased at higher Na(+) concentration in the injection water, but
      decreased in the presence of other cations in the groundwater. Field results with
      injection of elevated O(2) concentrations (0.55 mM) showed increased Fe removal
      efficacy; the operational parameter V/Vi (abstraction volume with [Fe]<2 MUM
      divided by the injection volume) increased from an average 7 to 16, indicating
      that not the exchangeable Fe(2+) on the soil material is the limiting factor
      during injection, but it is the supply of O(2) to the available Fe(2+).

PMID- 22137451
TI  - Transradial approach in the catheterization laboratory: pros/cons and suggestions
      for successful implementation.
AB  - In the last decade the radial access use in the catheterization laboratory has
      sensibly grown up worldwide. From an initial sporadic use as alternative but
      challenging vascular approach, radial artery is today utilized by default for
      percutaneous procedures in many centers. The tangible interest in the transradial
      approach is also testified by increasing presence of specific sessions in the
      main interventional meetings and by continuous development of dedicated catheters
      and ancillary devices by manufacturers. In this review we describe the anatomical
      characteristics and the technical aspects related to transradial procedure
      underlying its pros/cons in opposition to femoral access. We also point up
      practical instructions trying to resolve the main concerns related to an
      extensive use of radial approach in catheterization laboratory, such as increased
      operator's discomfort, higher radiation exposure, safety and feasibility for
      complex high-risk procedures.

PMID- 22137450
TI  - Cardiothoracic ratio from postero-anterior chest radiographs: a simple,
      reproducible and independent marker of disease severity and outcome in adults
      with congenital heart disease.
AB  - OBJECTIVE: The wide spectrum of intracardiac anatomy and reparative surgery
      available for adults with congenital heart disease (ACHD) makes uniform
      measurement of cardiac size and disease severity challenging. The aim of this
      study was to assess the prognostic potential of cardiothoracic ratio, a simple
      marker of cardiomegaly, in a large cohort of ACHD. PATIENTS AND SETTING: Chest
      radiographs from 3033 ACHD patients attending our institution between 1998 and
      2007 and 113 normal controls of similar age were analyzed blindly. DESIGN:
      Cardiothoracic ratio derived from plain postero-anterior chest radiographs, was
      compared between ACHD patients and controls, different diagnostic subgroups and
      different functional classes. Relationship between cardiothoracic ratio and
      survival was assessed using Cox regression. RESULTS: Average cardiothoracic ratio
      in ACHD was 52.0+/-7.6% (over 50% in 56.4%), significantly higher in all ACHD
      diagnostic subgroups compared to controls (42.3+/-4.0%, p<0.0001) and highest in
      the "complex" cardiac anatomy, Ebstein's anomaly and Eisenmenger subgroups.
      Cardiothoracic ratio related to functional class, but was high even in
      asymptomatic patients. During a median follow-up of 4.2years, 164 patients died.
      Patients with a cardiothoracic ratio >55% had an 8-fold increased risk of death
      compared to those in the lowest tertile (<48%). Even patients with mildly
      increased cardiothoracic ratio (48-55%) had an adjusted 3.6-fold increased
      mortality compared to the lowest tertile. CONCLUSIONS: Cardiothoracic ratio
      derived from postero-anterior chest radiographs is a simple, and reproducible
      marker, which relates to functional class and predicts independently mortality
      risk in ACHD patients.

PMID- 22137452
TI  - The potential for probiotic manipulation of the gastrointestinal microbiome.
AB  - Multiple internal and external sites of the healthy human body are colonized by a
      diversity of symbiotic microbes. The microbial assemblages found in the intestine
      represent some of the most dense and diverse of these human-associated
      ecosystems. Unsurprisingly, the enteric microbiome, that is the totality of
      microbes, their combined genomes, and their interactions with the human body, has
      a profound impact on physiological aspects of mammalian function, not least, host
      immune response. Lack of early-life exposure to certain microbes, or shifts in
      the composition of the gastrointestinal microbiome have been linked to the
      development and progression of several intestinal and extra-intestinal diseases,
      including childhood asthma development and inflammatory bowel disease. Modulating
      microbial exposure through probiotic supplementation represents a long-held
      strategy towards ameliorating disease via intestinal microbial community
      restructuring. This field has experienced somewhat of a resurgence over the past
      few years, primarily due to the exponential increase in human microbiome studies
      and a growing appreciation of our dependence on resident microbiota to modulate
      human health. This review aims to review recent regulatory aspects related to
      probiotics in food. It also summarizes what is known to date with respect to
      human gastrointestinal microbiota - the niche which has been most extensively
      studied in the human system - and the evidence for probiotic supplementation as a
      viable therapeutic strategy for modulating this consortium.

PMID- 22137453
TI  - Quantitative measurement of single cell dynamics.
AB  - Over the past 20 years luminescent and fluorescent imaging assays have been
      developed to report on the dynamics of transcription and protein translocation in
      single cells. The combination of these measurements with mathematical analysis is
      having an increasingly significant impact on cell biology. There is an urgent
      need to translate these assays to the study of cells and tissues in vivo, which
      requires new tools and technologies. Emergence of these new tools and techniques
      will further the understanding of the role of signalling and transcriptional
      dynamics in the generation of cellular heterogeneity and the control of cell
      fate.

PMID- 22137455
TI  - Determination of bioactive compounds in fermented soybean products using GC/MS
      and further investigation of correlation of their bioactivities.
AB  - The active ingredients and bioactivities (anti-oxidant, anti-tyrosinase, anti
      proliferative and estrogenic activities) of soybean and soybean products
      (Cheonggukjang, Meju, Makjang, Doenjang and soy sauce) produced by different
      fermentation processes were compared. There were high correlations between active
      ingredients and bioactivities. Free phenolic acids extracted from soybean
      products were identified and quantified by gas chromatography/mass spectrometry
      (GC/MS). Overall, the components and activities in fermented soybean products
      were different than those in soybeans. Total phenolic content (TPC), protein
      content (PC) and anti-oxidant activity increased as fermentation time increased.
      TPC and PC showed strong negative correlations with anti-oxidant activity.
      Doenjang and soy sauce, two long-term fermented products, showed lower total
      flavonoid content (TFC) and estrogenic activities than short-term fermented
      soybean products. This might be explained by the decomposition and hydrolysis of
      flavonoids due to the long fermentation time and high temperature. Strong anti
      proliferative activity against cancer cell lines, which was highly correlated
      with TFC, was found in Meju and Cheonggukjang. Soybean and all fermented products
      except Meju exhibited effective tyrosinase inhibitory activities. Fermented
      products showed stronger estrogenic activity than soybeans, which was highly
      correlated with syringic acid.

PMID- 22137454
TI  - Priming microenvironments dictate cytokine requirements for T helper 17 cell
      lineage commitment.
AB  - Activation of pattern recognition receptors on dendritic cells (DCs) and
      macrophages leads to secretion of cytokines that control differentiation of
      CD4(+) T cells. The current understanding is that interleukin-6 (IL-6) in
      combination with transforming growth factor-beta (TGF-beta) leads to generation
      of T helper 17 (Th17) lineage cells. Here, we have discovered that the cytokine
      requirements for Th17 cell polarization depend on the site of priming. Although
      IL-6 played a critical role in Th17 cell lineage priming in the skin and mucosal
      tissues, it was not required for Th17 cell priming in the spleen. In contrast, IL
      1 played an irreplaceable role for priming of Th17 lineage cells in all tissues.
      Importantly, we have demonstrated that IL-6-independent and -dependent pathways
      of Th17 cell differentiation are guided by DCs residing in various tissues. These
      results reveal fundamental differences by which the systemic, mucosal, and
      cutaneous immune systems guide Th17 cell lineage commitment.

PMID- 22137456
TI  - Verification and quantification of saxitoxin from algal samples using fast and
      validated hydrophilic interaction liquid chromatography-tandem mass spectrometry
      method.
AB  - Hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC
      MS/MS) method was validated with algal samples for verification and
      quantification of saxitoxin (STX), a potent neurotoxin which is listed in the
      Chemical Weapons Convention (CWC) in Schedule 1A. Isocratic elution, conventional
      bore HILIC column and high flow rate together with accurate post-column splitter
      provided detection of STX in 6.5 min with total analysis time of 9 min per
      sample. STX analogue, gonyautoxin 1 (GTX 1) was used as an internal standard.
      Sample preparation of freeze-dried algae included liquid extraction and
      centrifugal filtering with mean recovery of 99.9% at concentration level of 10
      ng/ml (n=3). Retention times for STX and GTX 1 were 6.47+/-0.03 min and 4.44+/
      0.01 min (n=45), respectively. Four diagnostic product ions were used for
      reliable verification of saxitoxin. Method was found to be precise and linear
      (R(2)=0.9714 and R(2)=0.9768) in concentration ranges of 5-50 ng/ml and 25-200
      ng/ml, respectively. For saxitoxin, calculated LOD was 3 ng/ml and LLOQ 11 ng/ml.
      Validation was conducted using spiked algal matrix since this method is not only
      needed for verification analysis for the CWC but also for safety analysis of
      other environmental samples for presence of STX. Identification criteria for
      verification of STX with HILIC-MS/MS method are discussed.

PMID- 22137457
TI  - Fragment based lead discovery of small molecule inhibitors for the EPHA4 receptor
      tyrosine kinase.
AB  - The in silico identification, optimization and crystallographic characterization
      of a 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine scaffold as an
      inhibitor for the EPHA4 receptor tyrosine kinase is described. A database
      containing commercially available compounds was subjected to an in silico
      screening procedure which was focused on finding novel, EPHA4 hinge binding
      fragments. This resulted in the identification of 6,7,8,9-tetrahydro-3H
      pyrazolo[3,4-c]isoquinolin-1-amine derivatives as EPHA4 inhibitors. Hit
      exploration yielded a compound with 2 MUM (IC(50)) affinity for the EPHA4
      receptor tyrosine kinase domain. Soaking experiments into a crystal of the EPHA4
      kinase domain gave a 2.11A X-ray structure of the EPHA4 - inhibitor complex,
      which confirmed the binding mode of the scaffold as proposed by the initial in
      silico work. The results underscore the strength of fragment based in silico
      screening as a tool for the discovery of novel lead compounds as small molecule
      kinase inhibitors.

PMID- 22137458
TI  - Design, synthesis, antiviral and cytostatic evaluation of novel isoxazolidine
      nucleotide analogues with a 1,2,3-triazole linker.
AB  - Azidation (TMSN(3), SnCl(4)) of a 9:1 mixture of trans- and cis-5-acetoxy-2
      methylisoxazolidin-3-yl-3-phosphonates at the anomeric carbon atom led to the
      formation of the equimolar mixture of cis- and trans-5-azido-2-methylisoxazolidin
      3-yl-3-phosphonates, which were efficiently separated. The 1,3-dipolar
      cycloaddition of pure trans- and cis-5-azidoisoxazolidin-3-yl-3-phosphonates with
      selected alkynes gave the respective nucleoside mimetics containing a 1,2,3
      triazole linker. The (1,2,3-triazolyl)isoxazolidine phosphonates obtained herein
      were evaluated in vitro for activity against a variety of DNA and RNA viruses.
      None of the compounds were endowed with antiviral activity at subtoxic
      concentrations. Compounds 15f-j and 16f-j were cytostatic in the higher
      micromolar range.

PMID- 22137459
TI  - Prevalence of oropharyngeal dysphagia in Parkinson's disease: a meta-analysis.
AB  - Dysphagia is a potentially harmful feature, also in Parkinson's disease (PD). As
      published prevalence rates vary widely, we aimed to estimate the prevalence of
      oropharyngeal dysphagia in PD in a meta-analysis. We conducted a systematic
      literature search in February 2011 and two independent reviewers selected the
      papers. We computed the estimates of the pooled prevalence weighted by sample
      size. Twelve studies were suitable for calculating prevalence rates. Ten studies
      provided an estimate based on subjective outcomes, which proved statistically
      heterogeneous (p < 0.001), with a pooled prevalence estimate with random effect
      analysis of 35% (95% CI 28-41). Four studies provided an estimate based on
      objective measurements, which were statistically homogeneous (p = 0.23), with a
      pooled prevalence estimate of 82% (95% CI 77-87). In controls the pooled
      subjective prevalence was 9% (95% CI 2-17), while the pooled objective prevalence
      was 23% (95% CI 13-32). The pooled relative risk was 3.2 for both subjective
      outcomes (95% CI 2.32-4.41) and objective outcomes (95% CI 2.08-4.98). Clinical
      heterogeneity between studies was chiefly explained by differences in disease
      severity. Subjective dysphagia occurs in one third of community-dwelling PD
      patients. Objectively measured dysphagia rates were much higher, with 4 out of 5
      patients being affected. This suggests that dysphagia is common in PD, but
      patients do not always report swallowing difficulties unless asked. This
      underreporting calls for a proactive clinical approach to dysphagia, particularly
      in light of the serious clinical consequences.

PMID- 22137460
TI  - Cerebellar axial postural tremor complicating radiotherapy for prostate cancer.

PMID- 22137461
TI  - The association between self-disorders and neurocognitive dysfunction in
      schizophrenia.
AB  - BACKGROUND: Neurocognitive deficits and self-disorders (i.e. altered basic self
      awareness or - sense of self) have both been suggested as fundamental trait
      features of schizophrenia. However, no study until now has investigated the
      relationship between these two core features. AIM: To investigate the
      relationship between self-disorders and neurocognitive performance in patients
      with schizophrenia. METHOD: Self-disorders were assessed in 57 patients in the
      early phase of schizophrenia by means of the Examination of Anomalous Self
      Experience (EASE) instrument. The neurocognitive assessments included measures of
      psychomotor speed, working memory, executive- and memory functions. RESULTS:
      There were few associations between self-disorders and neurocognitive
      impairments. However, high levels of SDs were significantly associated with
      impaired verbal memory. CONCLUSION: The reason for the general lack of
      associations between self-disorders and neurocognition could be that they
      represent different basic features of the illness. Verbal memory may however be
      linked to deficits in the patients' ability to comprehend, direct, remember and
      reason about their thoughts, functions that are intimately related to the basic
      sense of self.

PMID- 22137463
TI  - The hierarchical model of social interaction anxiety and depression: the critical
      roles of fears of evaluation.
AB  - In this paper, we articulate a hierarchical model of social interaction anxiety
      (SIA) and depression to account for their comorbidity and the uniqueness of SIA.
      First, negative affect (NA) and positive affect (PA) are conceptualized as
      general factors shared by SIA and depression; the fear of negative evaluation
      (FNE) is operationalized as the specific factor, which accounts for more of the
      variance in SIA than in depression, and the fear of positive evaluation (FPE) is
      operationalized as the factor unique to SIA. FPE is the key feature that
      differentiates SIA from depression. Second, the proposed hierarchical model
      describes structural relationships among these factors, in which the higher-level
      factors (i.e., high NA and low PA) represent the vulnerability markers of both
      SIA and depression and the lower-level factors (i.e., FNE and FPE) are the
      dimensions of specific cognitive features. In addition, an alternative model, in
      which all of the relationships are the same, except that FPE is operationalized
      as a specific factor, is proposed to clarify the role of FPE. The results from
      the hierarchical regression and the structural equation modeling support the
      hypothesized hierarchical model. Further theoretical and practical implications
      for FPE and the multilevel model are discussed.

PMID- 22137462
TI  - Rimonabant for neurocognition in schizophrenia: a 16-week double blind randomized
      placebo controlled trial.
AB  - OBJECTIVE: To examine the effect of rimonabant on neurocognitive impairments in
      people with schizophrenia. METHODS: Participants entered a 16-week double-blind,
      placebo-controlled, randomized clinical trial. A neurocognitive battery was
      administered at baseline and end of study. RESULTS: In comparison to rimonabant
      (20mg/day), placebo-treated participants exhibited a significant improvement on
      the Repeatable Battery for the Assessment of Neuropsychological Status total
      score. In contrast, rimonabant was associated with significant improvement on a
      probabilistic learning task. There were no other significant treatment effects.
      CONCLUSIONS: Rimonabant did not improve global cognitive functioning, but did
      improve a specific learning deficit based on response to positive feedback.

PMID- 22137464
TI  - The effects of dissociation on information processing for analogue trauma and
      neutral stimuli: a laboratory study.
AB  - This study investigated the effects of high and low levels of dissociation on
      information processing for analogue trauma and neutral stimuli. Fifty-four
      undergraduate females who reported high and low levels of trait dissociation were
      presented with two films, one depicting traumatic events, the other containing
      neutral material. Participants completed a divided attention task (yielding a
      proxy measure of attention), as well as explicit memory (free-recall) and
      implicit memory (word-stem completion) tasks for both films. Results indicated
      that the high DES group showed less attention and had poorer recall for the
      analogue trauma stimuli, relative to the neutral stimuli and the low DES group.
      These findings suggest that high levels of trait dissociation are associated with
      reductions in attention and memory for analogue trauma stimuli, relative to
      neutral stimuli and relative to low trait dissociation. Implications for the role
      of cognitive factors in the etiology of negative post-trauma responses are
      discussed.

PMID- 22137465
TI  - Cyberchondriasis: fact or fiction? A preliminary examination of the relationship
      between health anxiety and searching for health information on the Internet.
AB  - This study examined the relationship between health anxiety and searching for
      health information online, a phenomenon dubbed 'cyberchondria'. The majority of
      those with 'high' (n=46) and 'low' (n=36) levels of health anxiety reported
      seeking health information online. However, those with higher levels of health
      anxiety sought online health information more frequently, spent longer searching,
      and found searching more distressing and anxiety provoking. Furthermore, more
      responses in the high than low health anxiety group related to searching for
      information on diagnosed and undiagnosed medical conditions, descriptions of
      others' experiences of illnesses and using message boards/support groups,
      although the largest proportion of responses in both groups was accounted for by
      seeking information on symptoms. Linear regression (n=167) revealed significant
      relationships between health anxiety and the frequency, duration and distress and
      anxiety associated with searching for health information online. This preliminary
      data suggests that searching for health information online may exacerbate health
      anxiety.

PMID- 22137466
TI  - Electron microscopic demonstration and evaluation of irreversible electroporation
      induced nanopores on hepatocyte membranes.
AB  - PURPOSE: To demonstrate, evaluate, and verify the existence of irreversible
      electroporation (IRE)-ablation induced nanopores on the plasma membrane of
      hepatocytes. MATERIALS AND METHODS: On animal research committee approval, four
      New Zealand rabbits and two Yorkshire swine underwent IRE ablation of the liver
      (90 pulses, 100 MUs per pulse at 2,500 V), and selected ablated liver tissues
      were harvested, fixed, and air-dried according to the electron microscopy (EM)
      protocol. A scanning electron microscope (SEM; Nova 230 NanoSEM [FEI, Hillsboro,
      Oregon] with 80 picoamperes and 10-kV acceleration) was used to visualize and
      verify IRE-created nanopores. Using NIH image (Bethesda, Maryland) and ImageScope
      (Aperio Inc., Vista, California), 21 ablated tissues (16 rabbit, 5 swine) were
      evaluated. Corresponding hematoxylin and eosin (H&E) evaluation was performed to
      verify IRE-induced cell death. RESULTS: In all 21 IRE-ablated tissues, the SEM
      was able to show numerous, well-circumscribed, round, and concave-shaped pore
      defects disturbing the hepatocyte plasma membranes. These pores were not seen in
      normal liver. The size of the nanopores ranged from 80-490 nm with the greatest
      frequency of pores in bimodal distribution. The highest frequency of pore size
      was noted at the size range 340-360 nm. CONCLUSIONS: IRE induces nanopores on
      hepatocyte membranes, as shown by SEM. The pore diameters are larger than
      nanopores created by reversible electroporation (RE), which may have implications
      for irreversibility or permanency.

PMID- 22137467
TI  - Foreword. Mechanisms underlying our cognitive functions.

PMID- 22137468
TI  - Editorial. Representations of time.

PMID- 22137469
TI  - Castleman disease infiltrating great vessels and right atrium.

PMID- 22137470
TI  - Abdominal aortic dilatation during pregnancy in Marfan syndrome.

PMID- 22137471
TI  - Cholinergic circuits integrate neighboring visual signals in a Drosophila motion
      detection pathway.
AB  - Detecting motion is a feature of all advanced visual systems [1], nowhere more so
      than in flying animals, like insects [2, 3]. In flies, an influential
      autocorrelation model for motion detection, the elementary motion detector
      circuit (EMD; [4, 5]), compares visual signals from neighboring photoreceptors to
      derive information on motion direction and velocity. This information is fed by
      two types of interneuron, L1 and L2, in the first optic neuropile, or lamina, to
      downstream local motion detectors in columns of the second neuropile, the
      medulla. Despite receiving carefully matched photoreceptor inputs, L1 and L2
      drive distinct, separable pathways responding preferentially to moving "on" and
      "off" edges, respectively [6, 7]. Our serial electron microscopy (EM) identifies
      two types of transmedulla (Tm) target neurons, Tm1 and Tm2, that receive
      apparently matched synaptic inputs from L2. Tm2 neurons also receive inputs from
      two retinotopically posterior neighboring columns via L4, a third type of lamina
      neuron. Light microscopy reveals that the connections in these L2/L4/Tm2 circuits
      are highly determinate. Single-cell transcript profiling suggests that nicotinic
      acetylcholine receptors mediate transmission within the L2/L4/Tm2 circuits,
      whereas L1 is apparently glutamatergic. We propose that Tm2 integrates sign
      conserving inputs from neighboring columns to mediate the detection of front-to
      back motion generated during forward motion.

PMID- 22137472
TI  - Actin depolymerization-based force retracts the cell rear in polarizing and
      migrating cells.
AB  - In migrating cells, the relative importance of myosin II contractility for cell
      rear retraction varies [1-12]. However, in myosin II-inhibited polarizing cells,
      actin organization is compromised [13-18]; thus it remains unclear whether myosin
      II is simply required for correct actin arrangement or also directly drives rear
      retraction [9]. Ascaris sperm cells lack actin and associated motors, and
      depolymerization of major sperm protein is instead thought to pull the cell rear
      forward [19, 20]. Opposing views exist on whether actin could also have this
      function [19, 20] and has not been directly experimentally sought. We probe
      function at high temporal resolution in polarizing fibroblasts that establish
      migration by forming the cell rear first [9, 15, 21]. We show that in cells with
      correctly organized actin, that actin filament depolymerization directly drives
      retraction of the rear margin to polarize cells and spatially accounts for most
      cell rear retraction during established migration. Myosin II contractility is
      required early, to form aligned actin bundles that are needed for polarization,
      and also later to maintain bundle length that ensures directed protrusion at the
      cell front. Our data imply a new mechanism: actin depolymerization-based force
      retracts the cell rear to polarize cells with no direct contribution from myosin
      II contractility.

PMID- 22137473
TI  - Shaping fission yeast cells by rerouting actin-based transport on microtubules.
AB  - Kinesins and myosins transport cargos to specific locations along microtubules
      and actin filaments, respectively. The relative contribution of the two transport
      systems for cell polarization varies extensively in different cell types, with
      some cells relying exclusively on actin-based transport while others mainly use
      microtubules. Using fission yeast, we asked whether one transport system can
      substitute for the other. In this organism, microtubules and actin cables both
      contribute to polarized growth by transporting cargos to cell poles, but with
      distinct roles: microtubules transport landmarks to label cell poles for growth
      and actin assembly but do not directly contribute to the growth process [1].
      Actin cables serve as tracks for myosin V delivery of growth vesicles to cell
      poles [2-4]. We engineered a chimera between the motor domain of the kinesin 7
      Tea2 and the globular tail of the myosin V Myo52, which we show transports Ypt3,
      a myosin cargo receptor, to cell poles along microtubules. Remarkably, this
      chimera restores polarized growth and viability to cells lacking actin cables. It
      also bypasses the normal microtubule-dependent marking of cell poles for
      polarized growth, but not for other functions. Thus, a synthetic motor protein
      successfully redirects cargos along a distinct cytoskeletal route.

PMID- 22137474
TI  - LIN-42/PERIOD controls cyclical and developmental progression of C. elegans
      molts.
AB  - BACKGROUND: Biological timing mechanisms that integrate cyclical and successive
      processes are not well understood. C. elegans molting cycles involve rhythmic
      cellular and animal behaviors linked to the periodic reconstruction of cuticles.
      Molts are coordinated with successive transitions in the temporal fates of
      epidermal blast cells, which are programmed by genes in the heterochronic
      regulatory network. It was known that juveniles molt at regular 8-10 hr
      intervals, but the anticipated pacemaker had not been characterized. RESULTS: We
      find that inactivation of the heterochronic gene lin-42a, which is related to the
      core circadian clock gene PERIOD (PER), results in arrhythmic molts and
      continuously abnormal epidermal stem cell dynamics. The oscillatory expression of
      lin-42a in the epidermis peaks during the molts. Further, forced expression of
      lin-42a leads to anachronistic larval molts and lethargy in adults. CONCLUSIONS:
      Our results suggest that rising and falling levels of LIN-42A allow the start and
      completion, respectively, of larval molts. We propose that LIN-42A and affiliated
      factors regulate molting cycles in much the same way that PER-based oscillators
      drive rhythmic behaviors and metabolic processes in mature mammals. Further, the
      combination of reiterative and stage-specific functions of LIN-42 may coordinate
      periodic molts with successive development of the epidermis.

PMID- 22137476
TI  - Extracts from hardwood trees used in commercial paper mills contain biologically
      active neurochemical disruptors.
AB  - Following on our discovery that pulp and paper mill effluents can interact with,
      and disrupt, various neurotransmitter receptors and enzymes important to fish
      reproduction, we tested wood and bark extracts of 14 Eastern North American
      hardwood trees used in pulp and paper production. Radioligand binding to
      neurotransmitter receptors, including the dopamine-2 receptor (D2), the gamma
      aminobutyric acid receptor A (GABA(A)), N-methyl-D-aspartic acid (NMDA) receptor,
      and muscarinic cholinergic receptor (mACh-R), were significantly changed
      following in vitro incubations with many but not all extracts. Activities of
      neurotransmitter-related enzymes monoamine oxidase (MAO), GABA-transaminase (GABA
      T), acetylcholinesterase (AChE) and glutamic acid decarboxylase (GAD) were also
      significantly altered. Butternut wood extracts and the isolated compound juglone
      significantly inhibited the enzymatic activities of MAO and GAD which we suggest
      may be part of a mechanism that may negatively affect fish reproduction. Besides
      giving credence to the hypothesis that neuroactive compounds in pulp and paper
      effluent may originate in the trees used by mills, the results reported here also
      indicate important neuropharmacological activities in hardwoods which may help
      identify new sources of biologically active natural products.

PMID- 22137475
TI  - Optical reversal of halothane-induced immobility in C. elegans.
AB  - Volatile anesthetics (VAs) cause profound neurological effects, including
      reversible loss of consciousness and immobility. Despite their widespread use,
      the mechanism of action of VAs remains one of the unsolved puzzles of
      neuroscience [1, 2]. Genetic studies in Caenorhabditis elegans [3, 4], Drosophila
      [3, 5], and mice [6-9] indicate that ion channels controlling the neuronal
      resting membrane potential (RMP) also control anesthetic sensitivity. Leak
      channels selective for K(+) [10-13] or permeable to Na(+) [14] are critical for
      establishing RMP. We hypothesized that halothane, a VA, caused immobility by
      altering the neuronal RMP. In C. elegans, halothane-induced immobility is acutely
      and completely reversed by channelrhodopsin-2 based depolarization of the RMP
      when expressed specifically in cholinergic neurons. Furthermore, hyperpolarizing
      cholinergic neurons via halorhodopsin activation increases sensitivity to
      halothane. The sensitivity of C. elegans to halothane can be altered by 25-fold
      by either manipulation of membrane conductance with optogenetic methods or
      generation of mutations in leak channels that set the RMP. Immobility induced by
      another VA, isoflurane, is not affected by these treatments, thereby excluding
      the possibility of nonspecific hyperactivity. The sum of our data indicates that
      leak channels and the RMP are important determinants of halothane-induced general
      anesthesia.

PMID- 22137477
TI  - Pronounced reduction of fluoride exposure in free-ranging deer in North Bohemia
      (Czech Republic) as indicated by the biomarkers skeletal fluoride content and
      dental fluorosis.
AB  - Wild deer have been recommended as bioindicators of fluoride pollution. We
      compared bone fluoride concentrations and prevalence and severity of dental
      fluorosis in free-ranging European roe deer (Capreolus capreolus) and red deer
      (Cervus elaphus) from five counties in the northwestern part of the Czech
      Republic that had been collected by hunters and whose mandibles were presented at
      trophy exhibitions in the years 1996/1997 ("early period") and 2009 ("late
      period"). Data on atmospheric fluoride deposition suggested that the deer from
      the early period had been exposed to markedly higher fluoride levels than those
      from the late period. We therefore predicted a decline in skeletal fluoride
      levels and prevalence of dental fluorosis for both species from the early to the
      late period. Fluoride concentrations were determined in the coronoid process of
      the mandible, and assessment of dental fluorosis was performed on the permanent
      cheek teeth. A pronounced drop in fluoride concentrations from the early period
      (roe deer (n = 157), median: 3147 mg F(-)/kg of dry bone; red deer (n = 127),
      median: 1263 mg F(-)/kg of dry bone) to the late period (roe deer (n = 117),
      median: 350 mg F(-)/kg of dry bone; red deer (n = 72), median: 288 mg F(-)/kg of
      dry bone) was recorded. Prevalence of dental fluorosis also markedly declined
      from the early to the late period (roe deer: from 93% to 12%, red deer: from 87%
      to 28%). The reduction of fluoride deposition in the study area and, in
      consequence, fluoride exposure of the resident deer populations, is attributed
      largely to the implementation of emission control devices in the brown coal-fired
      power plants located in North Bohemia from the mid 1990s onwards. The findings of
      the present study demonstrate that wild deer are well suited for monitoring
      temporal changes in fluoride pollution of their habitats.

PMID- 22137478
TI  - Real-time estimation of small-area populations with human biomarkers in sewage.
AB  - A new approach is conceptualized for measuring small-area human populations by
      using biomarkers in sewage. The basis for the concept (SCIM: Sewage Chemical
      Information Mining) is supported by a comprehensive examination and synthesis of
      data published across several disciplines, including medicine, microbiology,
      clinical chemistry, and environmental science. Accurate measures of human
      populations are fundamental to numerous disciplines, including economics,
      marketing, politics, sociology, public health and safety (e.g., disease
      management; assessment of natural hazards; disaster prevention and response),
      quality of life, and the environment. Knowing the size, distribution, and flow of
      a small-area (local) population facilitates understanding the numerous and
      complex linkages and interactions between humans and the environment. Examples
      include material-flow (substance-flow) analysis, determining the magnitude of per
      capita contribution of pollutant loadings to watersheds, or forecasting future
      impacts of local populations on the environment or a population's demands on
      resources. While no definitive approach exists for measuring small-area
      populations, census-taking is a long-established convention. No approach exists,
      however, for gauging small-area populations in real-time, as none is able to
      capture population dynamics, which involve transient changes (e.g., daily influx
      and efflux) and lasting changes (e.g., births, deaths, change in residence).
      Accurate measurement of small-area populations in real time has never been
      possible but is essential for facilitating the design of more sustainable
      communities. Real-time measurement would provide communities the capability of
      testing what-if scenarios in design and policy decisions. After evaluation of a
      range of biomarkers (including the nitrogenous waste product creatinine, which
      has been long used in clinical chemistry as a parameter to normalize the
      concentrations of other urinary excretion products to account for urine
      dilution), the biomarker with the most potential for the SCIM concept for real
      time measurement of population was determined to be coprostanol - the major
      sterol produced by microbial reduction of cholesterol in the colon.

PMID- 22137479
TI  - Study on some factors affecting survivability of airborne fungi.
AB  - The aim of the present study was to investigate the effect of some air pollutants
      and meteorological parameters on the survivability of airborne fungi. Fungi were
      collected by using a slit impactor sampler calibrated to draw 20 L/min, for 3
      min. Nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), particulate matter (PM),
      relative humidity (RH %), temperature (T  degrees C) and wind speed (WS) were
      also measured. Air samples were taken during the period from March 2006 to
      February 2007. Fungal concentrations ranged between 45 and 451 CFU/m(3) with an
      annual mean concentration of 216 CFU/m(3). The lowest fungal concentration was
      found in the summer, however the highest one was found in the autumn. NO(2,)
      SO(2) and PM averaged 83.66 MUg/m(3), 67.01 MUg/m(3), and 237.69 MUg/m(3),
      respectively. T  degrees C was positively and negatively correlated with
      Aspergillus (P = 0.000) and Penicillium (P = 0.007), respectively. RH% was
      positively correlated with total fungi (P = 0.001), Aspergillus (P = 0.002) and
      Cladosporium (P = 0.047). Multiple regression analysis showed that T  degrees C
      and RH% were the most predicted variants. Non-significant correlations were found
      between fungal concentrations and air pollutants. Meteorological parameters were
      the critical factors affecting fungal survivability.

PMID- 22137480
TI  - Effect of bamboo biochar on pentachlorophenol leachability and bioavailability in
      agricultural soil.
AB  - In this study, bamboo biochar (BBC) was proposed as a practical carbonaceous
      material for the in situ remediation of organic pollutants. Column leaching
      experiments were used to evaluate the leachability of pentachlorophenol (PCP) in
      soil amended with BBC (0, 1, 2, and 5%; w/w). After leaching, the residual
      bioavailability of PCP in the soil column was determined by chemical extraction
      methods (methanol and distilled water). The results showed that compared to the
      control, the addition of 5% BBC decreased the cumulative leach-loss content of
      PCP by 42%, and also reduced PCP concentrations by 56 and 65% in methanol and
      distilled water extracts, respectively. Moreover, the linear leaching curves for
      the 10-h leaching time indicated that the rapid release process may be dependent
      on the continuous diffusion and partition mechanism. Regression analyses showed a
      significant (p<0.001) relationship between the BBC percentage and cumulative
      content of leached PCP, in addition, a significant relationship between BBC
      percentage and the chemical extraction of PCP with correlation coefficients
      (R(2)) greater than 0.9. Therefore, adding BBC to soil could prevent PCP further
      contamination such as bioavailability, surface or groundwater contamination
      through leaching.

PMID- 22137481
TI  - Tri-decabrominated diphenyl ethers and hexabromocyclododecane in indoor air and
      dust from Stockholm microenvironments 1: levels and profiles.
AB  - Indoor air (gas and particle phase) and dust samples were collected from 10
      houses, 44 apartments, 10 day care centers, 10 offices, 17 new cars and two car
      dealership halls from Stockholm, Sweden, and analyzed for polybrominated diphenyl
      ethers (PBDEs) and hexabromocyclododecane (HBCD). Median SigmaPBDE concentrations
      in air were 330, 58, 4000, 14000 and 510 pg/m(3) in houses, apartments, day care
      centers, offices and cars, respectively. Median SigmaPBDE concentrations in dust
      were 510, 1400, 1200, 1200 and 1400 ng/g in houses, apartments, day care centers,
      offices and cars, respectively. HBCD was detected in most dust samples (median
      range, 45-340 ng/g) but only in a few air samples (median range, <1.6-2.0
      pg/m(3)). For all microenvironments, the brominated flame retardant (BFR) found
      in highest concentration in air was SigmaDecaBDE, primarily BDE-209, followed by
      SigmaPentaBDE, and in dust, SigmaDecaBDE, followed by HBCD (offices, day care
      centers, cars) or SigmaPentaBDE (houses, apartments). Positive correlations were
      found between matched air and dust samples for SigmaPentaBDE, but not for
      SigmaDecaBDE.

PMID- 22137482
TI  - Targeting genetic and epigenetic alterations in the treatment of serous ovarian
      cancer.
AB  - Genomic information is being used to develop robust prognostic and predictive
      biomarkers that will provide companion diagnostics for emerging molecular
      targeted therapies. The genetics and associated molecular pathways in ovarian
      cancer are increasingly being used for the development of novel targeted drugs
      with a much greater therapeutic specificity than standard chemotherapy. This
      review will provide an update on recent research on the therapeutic opportunities
      presented by mutational alterations to the epidermal growth factor receptor
      (EGFR) and phosphatidylinositide-3-kinase (PI3K/AKT/mTOR) pathways. In addition,
      the role of the deficient BRCA1/2-mediated homologous recombination (HR)
      ("BRCAness") pathway is presented. Understanding the molecular biology of these
      pathways in the context of contemporary drug development means that somatic
      mutations and epigenetic losses of BRCA1/2 and PTEN in ovarian cancer are being
      used to predict sensitivity to new poly(ADP-ribose) polymerase (PARP) inhibitors
      that exhibit synthetic lethality with BRCA1/2 dysfunction and other repair
      pathways. Future predictive "biomarker pipelines" are being developed so that
      ovarian cancer patients will be able to avoid having treatments with drugs that
      will have no effect, whereas other patients with cancer may be eligible for
      therapies with a much higher probability of treatment response.

PMID- 22137483
TI  - Integrative genomic analysis identifies CCNB1 and CDC2 as candidate genes
      associated with meningioma recurrence.
AB  - Meningiomas are a common type of primary central nervous system tumor. Patients
      with atypical meningioma are difficult to treat and their disease often recurs.
      The aim of this study was to examine the role of CCNB1 and CDC2 as factors in
      recurrent meningiomas. A total of 37 sporadic meningioma samples were collected
      after surgery. The messenger RNA (mRNA) levels of the biomarkers CCNB1, CDC2, and
      MKI67 were tested using quantitative reverse transcription-polymerase chain
      reaction. We performed statistical analyses using ANOVA and Spearman correlation
      analysis. We found a significant upregulation in CCNB1 (1.5-fold), CDC2 (1.4
      fold), and MKI67 (1.8-fold) expression in recurrent tumors in comparison with
      primary tumors (P<0.05). Additionally, we found significant upregulation of CCNB1
      and MKI67 in recurrent tumors in comparison with primary tumors of benign
      meningiomas (P<0.05). We also compared the average change in expression level of
      the three genes (CCNB1, CDC2, and MKI67) in atypical/anaplastic versus benign
      meningiomas; the difference between the groups was highly significant (P<0.001).
      Our study indicates, for the first time, that an increased risk for sporadic
      benign meningioma recurrence can be found in cases with elevated expression of
      CCNB1. This suggests that expression of CCNB1 might be a potent tool for
      predicting the clinical prognosis of meningioma patients.

PMID- 22137484
TI  - High resolution genomic profiling and classical cytogenetics in a group of benign
      and atypical meningiomas.
AB  - Meningiomas are classified as benign, atypical, or anaplastic. The majority are
      sporadic, solitary, and benign tumors with favorable prognoses. However, the
      prognosis for patients with anaplastic meningiomas remains less favorable. High
      resolution genomic profiling has the capacity to provide more detailed
      information. Therefore, we analyzed genomic aberrations of benign and atypical
      meningiomas using single nucleotide polymorphism (SNP) array, combined with G
      banding by trypsin using Giemsa stain (GTG banding), spectral karyotyping, and
      locus-specific fluorescence in situ hybridization (FISH). We confirmed frequently
      detected chromosomal aberrations in meningiomas and identified novel genetic
      events. Applying SNP array, we identified constitutional de novo loss or gain
      within chromosome 22 in three patients, possibly representing inherited causal
      events for meningioma formation. We show evidence for somatic segmental
      uniparental disomy in regions 4p16.1, 7q31.2, 8p23.2, and 9p22.1 not previously
      described for primary meningioma. GTG-banding and spectral karyotyping detected a
      novel balanced reciprocal translocation t(4;10)(q12;q26) in one benign
      meningioma. A paracentric inversion within 1p36, previously described as novel,
      was detected as a recurrent chromosomal aberration in benign and atypical
      meningiomas. Analyses of tumors and matched normal tissues with a combination of
      SNP arrays and complementary techniques will help to further elucidate
      potentially causal genetic events for tumorigenesis of meningioma.

PMID- 22137485
TI  - HMGA2 and MDM2 expression in lipomatous tumors with partial, low-level
      amplification of sequences from the long arm of chromosome 12.
AB  - Ordinary lipomas are cytogenetically characterized primarily by simple balanced
      chromosome aberrations with stable morphologies, most of which affect chromosome
      segment, 12q13-15, where the HMGA2 gene plays a key pathogenetic role. Atypical
      lipomatous tumors (ALTs) display supernumerary ring or giant marker chromosomes
      with amplification of several genes including HMGA2 and MDM2. A study of HMGA2
      expression in a variety of adipocytic tumors showed aberrant expression in
      lipomas with 12q13-15 aberrations and ring chromosomes as well as in ALTs and
      well-differentiated liposarcomas (WDLSs), and frequent differential expression of
      HMGA2 exons 1-2 versus that of exons 4-5. A minor subset of adipocytic tumors
      harbors unbalanced karyotypes with extra copies of 12q sequences in structures
      that are not giant marker or ring chromosomes. Out of a series of ten such
      tumors, three lipomas and four ALTs with more than two copies of 12q13-15 and
      breakpoints in 12q13-15 could be analyzed by quantitative real-time polymerase
      chain reaction (qRT-PCR) to find out whether HMGA2 and MDM2 expression was more
      similar to the levels seen in lipomas with cytogenetically balanced aberrations
      of 12q13-15, or to ALTs with giant ring or marker chromosomes. One of two ALTs
      with more complex, hyperdiploid karyotypes had expression levels closer to those
      seen in ALT, whereas the remaining six cases were similar to lipomas with 12q13
      15 changes and ring chromosomes. Differential expression was seen in two ALTs and
      all three lipomas. Two cases showed MDM2 expression levels similar to those found
      among WDLSs, two cases showed levels similar to those found among lipomas,
      whereas the remaining three cases displayed intermediate expression levels. The
      studied cases represent intermediates between lipoma and ALT, insofar as they
      shared 12q13-15 rearrangements and karyotypic stability with lipomas and gain of
      12q sequences with ALTs. Neither of these characteristics can be used to
      discriminate between lipoma and ALT.

PMID- 22137486
TI  - A complex MLL rearrangement identified five years after initial MDS diagnosis
      results in out-of-frame fusions without progression to acute leukemia.
AB  - Chromosomal rearrangements of the MLL gene are uncommon in myelodysplastic
      syndromes (MDSs), and few studies of their molecular structures and oncogenic
      mechanisms exist. Here, we present a case of de novo MDS with a normal karyotype
      at initial diagnosis and a mild clinical course. Five years after the initial
      diagnosis, investigators identified a complex rearrangement of the MLL gene
      without progression to acute leukemia. The 5' part of the MLL gene is fused out
      of frame with the LOC100131626 gene, and the 3' part of the MLL gene out of frame
      with the TCF12 gene. Rapid amplification of complementary DNA 3' ends yielded two
      main fusion transcripts, which is in concordance with the two described isoforms
      of the LOC100131626 gene. For both isoform-fusion transcripts, the open reading
      frame terminates shortly after the breakpoint that is predicted to form two de
      facto truncated MLL proteins and disrupts the open reading frame of the
      LOC100131626, TCF12, and UBE4A genes. Neither dimerization nor a transcriptional
      activation domain, each of which is causally linked to MLL protein-mediated
      transformation, is present. This and other unusual MLL rearrangements probably
      represent a subclass of MLL gene abnormalities that have intrinsically no ability
      or only a weak ability to transform hematopoeitic cells and are identified only
      in the context of other hematopoetic malignancies.

PMID- 22137487
TI  - Double CEBPE-IGH rearrangement due to chromosome duplication and cryptic
      insertion in an adult with B-cell acute lymphoblastic leukemia.
AB  - In an adult case of B-cell acute lymphoblastic leukemia (B-ALL) with a complex
      karyotype, both chromosomes 14 were involved in unbalanced rearrangements,
      specifically, der(14)t(13;14)(q21;q21) and dup(14)(q11q32). Fluorescence in situ
      hybridization (FISH) detected two CEBPE-IGH rearrangements at the dup(14). One
      was found at the duplication breakpoint and the other derived from insertion of
      CEBPE into an apparently normal IGH locus. Hypotheses to account for these
      unusual chromosomal rearrangements are discussed. This case provides the first
      evidence that chromosome duplication and cryptic insertion produce the CEBPE-IGH
      fusion and that more than one CEBPE-IGH recombination can occur in a leukemic
      cell. Our findings confirm that deregulated CEBPE plays a crucial role in the
      pathogenesis of CEBPE-IGH positive B-ALL.

PMID- 22137488
TI  - Translocation t(2;11) is characteristic of collagenous fibroma (desmoplastic
      fibroblastoma).
AB  - Collagenous fibroma (desmoplastic fibroblastoma) is a rare, benign soft-tissue
      tumor composed of spindled and stellate-shaped cells embedded in a dense
      collagenous stroma. Recently, a translocation between chromosomes 2 and 11 or a
      rearrangement involving the chromosome 11q12 breakpoint was reported to be
      recurrent and unique in collagenous fibroma. Herein, we describe a case of
      collagenous fibroma arising in the left thigh of a 57-year-old man. Magnetic
      resonance imaging revealed a 5.5 cm soft-tissue mass deep relative to the vastus
      medialis with low signal intensity on both T1- and T2-weighted sequences. A
      marginal excision of the tumor was performed, and histopathologic features were
      consistent with collagenous fibroma. Cytogenetic analysis exhibited a reciprocal
      translocation involving the long arms of chromosomes 2 and 11. This finding
      suggests that the t(2;11) is likely to be of pathogenetic significance in a
      subset of collagenous fibromas.

PMID- 22137489
TI  - t(9;22)(q34;q11.2) is a recurrent constitutional non-Robertsonian translocation
      and a rare cytogenetic mimic of chronic myeloid leukemia.
AB  - The diagnosis of hematologic malignancy can be greatly aided by the detection of
      a cytogenetic abnormality. However, care must be taken to ensure that
      constitutional chromosomal abnormalities are not misattributed to a putative
      population of malignant cells. Here we present an unusual case in which a
      constitutional balanced t(9;22)(q34;q11.2) cytogenetically mimicked the acquired,
      t(9;22)(q34;q11.2), that is characteristic of chronic myeloid leukemia. Of
      special note, fluorescence in situ hybridization (FISH) analysis for this
      constitutional translocation (9;22)(q34;q11.2) using standard probes for BCR and
      ABL1 resulted in an abnormal pattern that was potentially misinterpretable as a
      BCR-ABL1 fusion. This is the first reported FISH analysis of a constitutional
      t(9;22)(q34;q11.2), and overall only the second report of such an abnormality. In
      light of the isolated prior report, our case also suggests that the
      constitutional t(9;22)(q34;q11.2) is one of the very few recurrent constitutional
      non-Robertsonian translocations described in humans. Our case underscores the
      necessity of complete clinical and laboratory correlation to avoid misdiagnosis
      of myeloid malignancy in the setting of rare constitutional cytogenetic
      abnormalities.

PMID- 22137490
TI  - Genetic polymorphisms in the P2X7 gene and its association with susceptibility to
      tuberculosis.
AB  - BACKGROUND: Several studies have reported the influence of genetic variations on
      susceptibility to tuberculosis (TB). Polymorphism in P2X7 gene coding for P2X7
      receptor present on macrophages has been linked to TB in different populations.
      OBJECTIVE: To assess the role of P2X7 gene -762T/C and -1513A/C polymorphisms in
      TB susceptibility. DESIGN: In a case-control study, polymerase chain reaction
      (PCR) amplification of genomic DNA extracted from peripheral blood samples of
      cases and controls was followed by restriction fragment length polymorphism or
      allele-specific PCR. RESULTS: The 1513C allele was found to be associated with TB
      susceptibility (P = 0.02, OR for variant C allele 1.33, 95%CI 1.03-1.73). A
      significant protective association against TB was found for -762T/C polymorphism
      (P < 0.01, OR for variant C allele 0.72, 95%CI 0.57-0.91). On classifying samples
      on the basis of sex, only males showed a significant association between P2X7 
      1513A/C and P2X7 -762T/C and TB in the present study. CONCLUSION: A significant
      association of 762T/C and 1513A/C polymorphisms with TB in the P2X7 gene was
      found in our study population. A sex bias, with only males showing a significant
      association with the disease, is the first report of this kind. Genetic studies
      for the characterisation of the susceptibility genes can help to gain a better
      understanding of TB pathogenesis.

PMID- 22137492
TI  - Normal live birth after testicular sperm extraction and intracytoplasmic sperm
      injection in variant primary ciliary dyskinesia with completely immotile sperm
      and structurally abnormal sperm tails.
AB  - OBJECTIVE: To report on the investigation and fertility management of variant
      primary ciliary dyskinesia (PCD). DESIGN: Case report. SETTING: University
      affiliated assisted reproductive technologies practice. PATIENT(S): A 40 year-old
      man presenting with 12 months' primary infertility, complete sperm immotility,
      severe morphologic defects, and moderate sinopulmonary disease. INTERVENTION(S):
      Electron microscopy (EM) of sperm, nasal cilial function studies, open testis
      biopsy, and sperm extraction for intracytoplasmic sperm injection (ICSI). MAIN
      OUTCOME MEASURE(S): Outcome of ICSI treatment using immotile testicular sperm.
      RESULT(S): EM revealed abnormal connecting pieces, shortened midpieces with
      attenuated mitochondrial sheaths, poorly developed annulus, abnormal outer dense
      fibers, and axonemes missing the two central mircotubules. Nasal ciliary beat
      frequency was subnormal and dyssynchronous. Immotile testicular sperm were
      selected for ICSI based on physical characteristics and fertilized 12 of 18 eggs.
      A single day-5 blastocyst achieved a normal pregnancy and delivery of a healthy
      3,840-g girl at 38 weeks' gestation. CONCLUSION(S): Nonclassic PCD may present
      with structurally abnormal completely immotile sperm, with seemingly little
      prospect of fertility, and moderate respiratory dysfunction supporting the
      presence of an underlying ciliopathy. Despite testicular sperm also being
      immotile and showing profound structural defects that would seem to preclude
      fertilization, more morphologically normal sperm are capable of establishing a
      normal pregnancy.

PMID- 22137491
TI  - Impact of cancer therapies on ovarian reserve.
AB  - OBJECTIVE: To determine whether measures of ovarian reserve differ between
      females exposed to cancer therapies in a dose-dependent manner as compared with
      healthy controls of similar age and late reproductive age. DESIGN: Cross
      sectional analysis of data from a prospective cohort study. SETTING: University
      medical center. PATIENT(S): Seventy-one cancer survivors aged 15-39 years; 67
      healthy, similarly aged unexposed subjects; and 69 regularly menstruating women
      of late reproductive age (40-52 years). INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Early follicular-phase hormones (FSH, E(2), inhibin B, antimullerian
      hormone [AMH]) and ovarian ultrasound measurements (ovarian volume and antral
      follicle counts [AFC]) were compared using multivariable linear regression.
      RESULT(S): In adjusted models, FSH, AMH, and AFC differed between exposed vs.
      unexposed subjects (FSH 11.12 mIU/mL vs. 7.25 mIU/mL; AMH 0.81 ng/mL vs. 2.85
      ng/mL; AFC 14.55 vs. 27.20). In participants with an FSH <10 mIU/mL, survivors
      had lower levels of AMH and AFC compared with controls. Alkylating agent dose
      score was associated with increased levels of FSH and decreased levels of AMH.
      Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC, and
      ovarian volume. Antimullerian hormone was similar in women previously exposed to
      high-dose cancer therapy and 40-42-year-old controls. CONCLUSION(S): Measures of
      ovarian reserve are impaired in a dose-dependent manner among cancer survivors
      compared with unexposed females of similar age. Reproductive hormone levels in
      menstruating survivors exposed to high-dose therapy are similar to those in late
      reproductive-age women. The predictive value of measures for pregnancy and
      menopause must be studied. CLINICALTRIALS.GOV IDENTIFIER: NCT01143844.

PMID- 22137493
TI  - Knowledge and attitudes regarding expanded genetic carrier screening among
      women's healthcare providers.
AB  - OBJECTIVE: To determine women's healthcare providers' knowledge and attitudes
      regarding genetic disorders and expanded genetic screening. DESIGN: Survey of
      American Society for Reproductive Medicine 2010 and American College of
      Obstetricians and Gynecologists 2011 Annual Meeting attendees. The survey
      included 60 items (12 demographic, 10 knowledge, and 38 attitude). Attitudes were
      assessed with a 5-point Likert scale. Chi-square or t tests determined
      significance. SETTING: American Society for Reproductive Medicine 2010 and
      American College of Obstetricians and Gynecologists 2011 Annual Meeting.
      PATIENT(S): A total of 203 participants completed the survey. Of these, 48% were
      male, 61% were physicians, 73% were Caucasian, and 42% were aged 35-50 years.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): Physicians had
      better knowledge scores than other participants (87% vs. 79%). Knowledge was not
      influenced by prior personal/family experience with genetic screening. Fewer
      correct answers were observed for the probability of a positive test (65.2%), the
      risk of transmitting a gene mutation (62.2%), and the risk of having an affected
      child (56.2%). Very few participants (18.3%) disagreed with the notion of carrier
      screening as socially responsible behavior. Some had concerns about test result
      confidentiality (40.1%) and resulting insurance rate increases (37.0%). Assuming
      equal costs, most participants preferred to be tested for a larger number of
      diseases (77.7%) and believed posttest counseling to be helpful (83.7%).
      CONCLUSION(S): Women's healthcare providers generally had good knowledge and
      positive attitudes about genetic disorders and expanded genetic screening.
      Specific misperceptions, both medical and legal, require education.

PMID- 22137494
TI  - Estriol administration modulates luteinizing hormone secretion in women with
      functional hypothalamic amenorrhea.
AB  - OBJECTIVE: To evaluate the influence of estriol administration on the
      hypothalamus-pituitary function and gonadotropins secretion in patients affected
      by functional hypothalamic amenorrhea (FHA). DESIGN: Controlled clinical study.
      SETTING: Patients with FHA in a clinical research environment. PATIENT(S): Twelve
      hypogonadotropic patients affected by FHA. INTERVENTION(S): Pulsatility study of
      luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and a
      gonadotropin-releasing hormone (GnRH) test (10 MUg in bolus) at baseline
      condition and after 8 weeks of therapy with 2 mg/day of estriol. MAIN OUTCOME
      MEASURE(S): Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione
      (A), 17alpha-hydroxyprogesterone (17-OHP), cortisol, androstenedione (A),
      testosterone (T), thyroid-stimulating hormone (TSH), free triiodothyronine
      (fT(3)), free thyroxine (fT(4)), and insulin, and pulse detection. RESULT(S):
      After treatment, the FHA patients showed a statistically significant increase of
      LH plasma levels (from 0.7 +/- 0.1 mIU/mL to 3.5 +/- 0.3 mIU/mL) and a
      statistically significant increase of LH pulse amplitude with no changes in LH
      pulse frequency. In addition, the LH response to the GnRH bolus was a
      statistically significant increase. CONCLUSION(S): Estriol administration induced
      the increase of LH plasma levels in FHA and improved GnRH-induced LH secretion.
      These findings suggest that estriol administration modulates the neuroendocrine
      control of the hypothalamus-pituitary unit and induces the recovery of LH
      synthesis and secretion in hypogonadotropic patients with FHA.

PMID- 22137495
TI  - Presence of spermatogonia in 47,XXY men with no spermatozoa recovered after
      testicular sperm extraction.
AB  - OBJECTIVE: To evaluate the presence of spermatogonia in men diagnosed with
      Klinefelter syndrome (KS), in whom no testicular spermatozoa were recovered by
      testicular sperm extraction. DESIGN: Retrospective case series. SETTING:
      University hospital. PATIENT(S): Testicular samples from 22 nonmosaic 47,XXY men,
      aged 24-43 years, with no spermatozoa at multiple biopsies. INTERVENTION(S):
      Paraffin-embedded testicular tissue was sectioned and stained with hematoxylin
      eosin, and immunostainings were performed for both MAGE-A4 and vimentin. MAIN
      OUTCOME MEASURE(S): The presence of spermatogonia. RESULT(S): Massive fibrosis
      and hyalinization were observed in all men with KS. Spermatogonia were observed
      in 4 of 22 men with KS, with differentiation up to the spermatocyte level in 2 of
      them. CONCLUSION(S): A few men with KS, having no spermatozoa after testicular
      sperm extraction, still had few spermatogonia. These patients may eventually
      benefit from in vitro maturation using spermatogonial stem cells. The adult KS
      population can thus be divided into three subgroups: one subgroup showing focal
      spermatogenesis, a second having spermatogonia, and a third group in which no
      germ cells can be recovered. Further research is necessary to unravel the
      mechanism leading to these different patterns in patients with KS.

PMID- 22137496
TI  - Should TSPYL1 mutation screening be included in routine diagnostics of male
      idiopathic infertility?
AB  - OBJECTIVE: To investigate a putative role of TSPYL1 in male idiopathic
      infertility. DESIGN: Clinical article. SETTING: University hospital. PATIENT(S):
      A total of 104 infertile men were selected with idiopathic nonobstructive
      azoospermia, cryptozoospermia, oligozoospermia, oligonecrozoospermia, and
      oligoasthenoteratozoospermia (OAT) syndrome, along with a control group of 106
      men with proven paternity. INTERVENTION(S): Mutation screening of the coding
      region and parts of the 5' and 3' untranslated regions of the TSPYL1 gene was
      performed by polymerase chain reaction and sequencing. MAIN OUTCOME MEASURE(S):
      Occurrence of TSPYL1 single-nucleotide polymorphisms (SNPs) and mutations.
      RESULT(S): In these cohorts, eight known TSPYL1 SNPs were identified, none of
      which was significantly associated with male infertility. Two potentially disease
      causing variants were detected in the infertile cohort: one man with azoospermia
      was found to be heterozygous for the novel TSPYL1 variant c.419C>G (p.Ser140Cys),
      and the rare substitution c.1098C>A (p.Phe366Leu) was identified in a man with
      OAT syndrome in the heterozygous state. Additionally, one fertile man was found
      to be heterozygous for the rare variant c.487G>A (p.Val163Ile). In silico
      analyses predicted a nonpathogenic effect for all amino acid exchanges, although
      protein features might be affected by p.Ser140Cys and p.Phe366Leu, respectively.
      CONCLUSION(S): Mutations in the TSPYL1 gene do not seem to play a major role in
      the pathogenesis of idiopathic male infertility, and mutation screening of the
      TSPYL1 gene can currently not be recommended in routine diagnostics of idiopathic
      male infertility.

PMID- 22137498
TI  - Strong linea alba: myth or reality?
AB  - The traditional approach of repairing the linea alba, while operating on ventral
      hernias, is based on the premise that the linea alba is a strong layer and can
      reinforce the abdominal wall. This deeply entrenched view of most surgeons has
      resulted in numerous techniques which invariably include the linea alba as a part
      of the repair. On the contrary, this article proposes a hypothesis that the linea
      alba is a weak layer and varies widely in individuals with respect to its
      anatomy. It is especially weak in elderly, obese and multiparous patients in whom
      ventral hernias are common. The 'white line' - literal translation of 'linea
      alba' - becomes wide and attenuated in these patients; this 'white area' or 'rus
      alba' is more susceptible to tissue failure. We termed this the "Sick Linea Alba
      Complex" (SLAC) and hypothesize that the linea alba should be excluded from
      rather than included in the repair of ventral hernias in order to minimize
      recurrence rates.

PMID- 22137497
TI  - Effects of transdermal testosterone on natriuretic peptide levels in women: a
      randomized placebo-controlled pilot study.
AB  - OBJECTIVE: To investigate whether testosterone administration alters natriuretic
      peptide levels in women. DESIGN: Three-month, double-blind, randomized, placebo
      controlled study. SETTING: Clinical research center. PATIENT(S): Fifty-one women
      with hypoandrogenemia due to hypopituitarism. INTERVENTION(S): Transdermal
      testosterone (300 MUg daily) or placebo patch. MAIN OUTCOME MEASURE(S): N
      Terminal pro-B-type natriuretic peptide (NT-proBNP) levels. RESULT(S): NT-proBNP
      levels decreased in the transdermal testosterone group compared with placebo over
      three months. The difference between groups remained significant after
      controlling for baseline age, systolic blood pressure, body mass index, and
      homeostasis model assessment of insulin resistance. Change in NT-proBNP over 3
      months was inversely associated with change in free testosterone levels.
      CONCLUSION(S): Testosterone administration to women results in decreased
      natriuretic peptide levels, suggesting that testosterone may be an inverse
      regulator of the natriuretic peptide system. CLINICAL TRIALS REGISTRATION NUMBER:
      NCT00027430.

PMID- 22137499
TI  - Can miniature pulpotomy procedure improve treatment outcomes of direct pulp
      capping?
AB  - Dental pulp exposure is a common incident during dental treatment. If there are
      clinical signs of pulp vitality, it is recommended to carry out direct pulp
      capping (DPC) using appropriate pulp covering agents (PCA). The main objectives
      are maintenance of pulp vitality/healing along with the formation of a calcified
      bridge beneath the PCA. Our proposed hypothesis is based on consideration of
      biologic principles in order to achieve improved treatment outcomes of DPC for
      cariously exposed pulp using miniature pulpotomy procedure (MPP). MPP will result
      in improved treatment outcomes of DPC by improved maintenance of a clean surgical
      pulp wound; removal of infected dentin chips/damaged pulp tissue specially
      injured odontoblast cells; improved proximity/interaction of PCA to
      undifferentiated mesenchymal/stem cells; better control of bleeding; and creating
      an improved seal using PCA.

PMID- 22137500
TI  - Interferon-inducible p200-family protein IFI16, an innate immune sensor for
      cytosolic and nuclear double-stranded DNA: regulation of subcellular
      localization.
AB  - The interferon (IFN)-inducible p200-protein family includes structurally related
      murine (for example, p202a, p202b, p204, and Aim2) and human (for example, AIM2
      and IFI16) proteins. All proteins in the family share a partially conserved
      repeat of 200-amino acid residues (also called HIN-200 domain) in the C-terminus.
      Additionally, most proteins (except the p202a and p202b proteins) also share a
      protein-protein interaction pyrin domain (PYD) in the N-terminus. The HIN-200
      domain contains two consecutive oligosaccharide/oligonucleotide binding folds (OB
      folds) to bind double stranded DNA (dsDNA). The PYD domain in proteins allows
      interactions with the family members and an adaptor protein ASC. Upon sensing
      cytosolic dsDNA, Aim2, p204, and AIM2 proteins recruit ASC protein to form an
      inflammasome, resulting in increased production of proinflammatory cytokines.
      However, IFI16 protein can sense cytosolic as well as nuclear dsDNA.
      Interestingly, the IFI16 protein contains a nuclear localization signal (NLS).
      Accordingly, the initial studies had indicated that the endogenous IFI16 protein
      is detected in the nucleus and within the nucleus in the nucleolus. However,
      several recent reports suggest that subcellular localization of IFI16 protein in
      nuclear versus cytoplasmic (or both) compartment depends on cell type. Given that
      the IFI16 protein can sense cytosolic as well as nuclear dsDNA and can initiate
      different innate immune responses (production of IFN-beta versus proinflammatory
      cytokines), here we evaluate the experimental evidence for the regulation of
      subcellular localization of IFI16 protein in various cell types. We conclude that
      further studies are needed to understand the molecular mechanisms that regulate
      the subcellular localization of IFI16 protein.

PMID- 22137501
TI  - Maternal parenting behaviors during childhood relate to weight status and fruit
      and vegetable intake of college students.
AB  - OBJECTIVE: Examine how maternal parenting behaviors in childhood, both general
      and feeding specific, relate to weight status and fruit and vegetable consumption
      in college students. DESIGN: Retrospective surveys on maternal behaviors and
      assessments on the college-aged child's current anthropometric measures and
      dietary intakes. PARTICIPANTS: College students (n = 424; 66% women). MAIN
      OUTCOME MEASURES: Students' weight, height, waist circumference, fruit and
      vegetable intakes, students' reports on mothers' general and feeding-specific
      parenting behaviors during childhood. ANALYSIS: Correlation and regression
      analyses tested how maternal behaviors in childhood related to students' body
      mass index, waist circumference, and fruit and vegetable intake. RESULTS:
      Mothers' psychological control during childhood was associated with higher body
      mass index and waist circumference in students, and behavioral control was
      associated with lower waist circumference. Parent-centered feeding behaviors
      related to lower fruit and vegetable intakes of students, whereas child-centered
      feeding behaviors related to higher fruit and vegetable intakes. CONCLUSIONS AND
      IMPLICATIONS: Findings suggest that parental use of behavioral control and child
      centered feeding practices and minimal use of psychological control and parent
      centered feeding practices during childhood may promote a child's healthful
      weight status and fruit and vegetable consumption in young adulthood,
      specifically during college.

PMID- 22137502
TI  - Cooperativity in monomeric enzymes with single ligand-binding sites.
AB  - Cooperativity is widespread in biology. It empowers a variety of regulatory
      mechanisms and impacts both the kinetic and thermodynamic properties of
      macromolecular systems. Traditionally, cooperativity is viewed as requiring the
      participation of multiple, spatially distinct binding sites that communicate via
      ligand-induced structural rearrangements; however, cooperativity requires neither
      multiple ligand binding events nor multimeric assemblies. An underappreciated
      manifestation of cooperativity has been observed in the non-Michaelis-Menten
      kinetic response of certain monomeric enzymes that possess only a single ligand
      binding site. In this review, we present an overview of kinetic cooperativity in
      monomeric enzymes. We discuss the primary mechanisms postulated to give rise to
      monomeric cooperativity and highlight modern experimental methods that could
      offer new insights into the nature of this phenomenon. We conclude with an
      updated list of single subunit enzymes that are suspected of displaying
      cooperativity, and a discussion of the biological significance of this unique
      kinetic response.

PMID- 22137503
TI  - Targeting the detection of chronic wasting disease using the hunter harvest
      during early phases of an outbreak in Saskatchewan, Canada.
AB  - Chronic wasting disease (CWD) is a fatal disease of North American cervids that
      was first detected in a wild, hunter-shot deer in Saskatchewan along the border
      with Alberta in Canada in 2000. Spatially explicit models for assessing factors
      affecting disease detection are needed to guide surveillance and control
      programs. Spatio-temporal patterns in CWD prevalence can be complicated by
      variation in individual infection probability and sampling biases. We assessed
      hunter harvest data of mule deer (Odocoileus hemionus) and white-tailed deer
      (Odocoileus virginianus) during the early phases of an outbreak in Saskatchewan
      (i.e., 2002-2007) for targeting the detection of CWD by defining (1) where to
      look, and (2) how much effort to use. First, we accounted for known demographic
      heterogeneities in infection to model the probability, P(E), that a harvested
      deer was infected with CWD given characteristics of the harvest location. Second,
      in areas where infected deer were harvested we modelled the probability, P(D), of
      the hunter harvest re-detecting CWD within sample units of varying size (9-54
      km(2)) given the demographics of harvested deer and time since first detection in
      the study area. Heterogeneities in host infection were consistent with those
      reported elsewhere: mule deer 3.7 times >white-tailed deer, males 1.8
      times>females, and quadratically related to age in both sexes. P(E) increased
      with number of years since the first detection in our study area (2002) and
      proximity to known disease sources, and also varied with distance to the South
      Saskatchewan River and small creek drainages, terrain ruggedness, and extent of
      agriculture lands within a 3 km radius of the harvest. The majority (75%) of new
      CWD-positive deer from our sample were found within 20 km of infected deer
      harvested in the previous year, while approximately 10% were greater than 40 km.
      P(D) modelled at 18 km(2) was best supported, but for all scales, P(D) depended
      on the number of harvested deer and time since the first infected deer was
      harvested. Within an 18 km(2) sampling unit, there was an 80% probability of
      detecting a CWD-positive deer with 16 harvested deer five years after the initial
      infected harvest. Identifying where and how much to sample to detect CWD can
      improve targeted surveillance programs early in the outbreak of the disease when
      based on hunter harvest.

PMID- 22137504
TI  - Vanadate-induced Ca(2+) and Co(2+) uptake in human red blood cells.
AB  - The vanadate-induced increase in passive uptake of calcium and cobalt and their
      interference were studied in human red cells using (45)Ca and (57)Co as tracers.
      Vanadate is a potent inhibitor of the Ca-pump in red cells, although in fed cells
      a residual pump activity remains that is highly significant compared to the
      passive influx, and even in cells that are both ATP-depleted and vanadate-treated
      the pump arrest is not complete. In the presence of vanadate the Ca(2+) uptake is
      increased due to inhibition of Ca-pump extrusion, but is further increased due to
      a vanadate-induced increment in passive influx. In order to measure the vanadate
      induced increment in Ca(2+) influx, the total uptake in vanadate-treated cells is
      corrected for the basal influx, as recorded in ATP-depleted cells in the presence
      of tetrathionate (5mM) that has been shown to eliminate the residual Ca-pump
      activity in ATP-depleted cells. The (57)Co uptake is also increased by vanadate.
      (57)Co is not transported by the Ca-pump, and hence the uptake in vanadate
      treated cells can be directly compared to the basal uptake, both in fed and in
      ATP-depleted cells. The vanadate effect shows rapid onset and appears to be
      irreversible. The vanadate-induced increment in uptake of both (45)Ca and (57)Co
      is reduced by about 50% in ATP-depleted cells compared to fed cells, suggesting a
      metabolism- or SH-group-dependent component. The influx of both (45)Ca (in ATP
      depleted cells) and (57)Co (in fed cells) increases with the vanadate
      concentration, with a similar K(1/2) (0.4 and 0.3mM, respectively), and is nearly
      maximal at 5mM vanadate. The vanadate-induced increment in influx of both (45)Ca
      and (57)Co increases with the extracellular concentration as a saturable
      function, with K(1/2) estimated at, respectively, 700 and 80MUM. In the case of
      (57)Co K(1/2) is similar in fed and in ATP-depleted cells. The vanadate-induced
      uptake of (45)Ca and of (57)Co shows interference. The uptake of (45)Ca is
      inhibited by Co(2+), and the uptake of (57)Co is inhibited by Ca(2+), although
      with an unexplained time course. The vanadate-induced uptake of (45)Ca and (57)Co
      are both inhibited, and to a similar degree, by the 1,4-dihydropyridine Ca(2+)
      channel blocker nifedipine, although only at concentrations much higher than
      IC(50) for classical Ca-channels. The vanadate-induced increment in (57)Co uptake
      is electroneutral, in contrast to the basal uptake that is at least partially
      electrogenic. In experiments with resealed ghosts a vanadate-induced (57)Co
      uptake could not be detected. The vanadate-induced increment in (57)Co uptake
      amounts to nearly half the increment in (45)Ca uptake, both in fed and in ATP
      depleted cells. It is speculated that the vanadate-induced Ca(2+) and Co(2+)
      uptake could be mediated by a putative common transporter, which appears to be
      separate and distinct from the putative common transporter for basal Ca(2+) and
      Co(2+) uptake.

PMID- 22137505
TI  - PER2 rs2304672 polymorphism moderates circadian-relevant reward circuitry
      activity in adolescents.
AB  - BACKGROUND: Reward behavior in animals is influenced by circadian genes,
      including clock-pathway genes such as Period2 (PER2). Several forms of
      psychiatric illness are associated with both altered reward function and
      disturbances in circadian function. The PER2 single nucleotide polymorphism (SNP)
      rs2304672 has been associated with psychiatric illnesses involving reward
      dysfunction. Associations among circadian genes, function in neural reward
      circuits, and circadian-influenced behavior have not yet been studied in humans,
      however. METHODS: 90 healthy adolescents underwent functional magnetic resonance
      imaging during a guessing task with monetary reward, genotyping for two PER2 SNPs
      (rs2304672, rs2304674), and actigraphy to measure sleep in their home
      environments. Weekend sleep midpoint, a behavioral index of circadian function,
      was derived from actigraphy. Puberty was measured by physical exam. RESULTS: The
      rs2304672 SNP predicted blood oxygenation level-dependent response to monetary
      reward as constrained by sleep midpoint. Later sleep midpoint was associated with
      reduced activity in a key component of reward circuitry, medial prefrontal cortex
      (mPFC; Brodmann area 9/10/32), to reward outcome (p(corrected) < .05). G allele
      carriers showed reduced activity in mPFC relative to CC homozygotes. CONCLUSIONS:
      Our findings are the first to indicate that circadian genes have a significant
      impact upon circadian-relevant reward circuitry in humans. These findings have
      the potential to elucidate gene-brain-behavior relationships underlying reward
      processing and psychopathology.

PMID- 22137508
TI  - New techniques and technologies for obstetric anaesthesia.

PMID- 22137507
TI  - Glucocorticoid receptor pathway components predict posttraumatic stress disorder
      symptom development: a prospective study.
AB  - BACKGROUND: Biological correlates of posttraumatic stress disorder (PTSD) have
      mostly been studied using cross-sectional or posttrauma prospective designs.
      Therefore, it remains largely unknown whether previously observed biological
      correlates of PTSD precede trauma exposure. We investigated whether
      glucocorticoid receptor (GR) pathway components assessed in leukocytes before
      military deployment represent preexisting vulnerability factors for development
      of PTSD symptoms. METHODS: Four hundred forty-eight male soldiers were assessed
      before and 6 months after deployment to a combat zone. Participants were assigned
      to the PTSD or comparison group based on Self-Rating Inventory for PTSD scores
      after deployment. Logistic regression analysis was applied to predict development
      of a high level of PTSD symptoms based on predeployment GR number, messenger
      (m)RNA expression of GR target genes FKBP5, GILZ, and SGK1, plasma cortisol, and
      childhood trauma. We also investigated whether predeployment GR number and FKBP5
      mRNA expression were associated with single nucleotide polymorphisms in the GR
      and FKBP5 genes, either alone or in interaction with childhood trauma. RESULTS:
      Several GR pathway components predicted subsequent development of a high level of
      PTSD symptoms: predeployment high GR number, low FKBP5 mRNA expression, and high
      GILZ mRNA expression were independently associated with increased risk for a high
      level of PTSD symptoms. Childhood trauma also independently predicted development
      of a high level of PTSD symptoms. Additionally, we observed a significant
      interaction effect of GR haplotype BclI and childhood trauma on GR number.
      CONCLUSIONS: Collectively, our results indicate that predeployment GR pathway
      components are vulnerability factors for subsequent development of a high level
      of PTSD symptoms.

PMID- 22137506
TI  - Synchrony of corticostriatal-midbrain activation enables normal inhibitory
      control and conflict processing in recovering alcoholic men.
AB  - BACKGROUND: Alcohol dependence is associated with inhibitory control deficits,
      possibly related to abnormalities in frontoparietal cortical and midbrain
      function and connectivity. METHODS: We examined functional connectivity and
      microstructural fiber integrity between frontoparietal and midbrain structures
      using a Stroop Match-to-Sample task with functional magnetic resonance imaging
      and diffusion tensor imaging in 18 alcoholic and 17 control subjects.
      Manipulation of color cues and response repetition sequences modulated cognitive
      demands during Stroop conflict. RESULTS: Despite similar lateral frontoparietal
      activity and functional connectivity in alcoholic and control subjects when
      processing conflict, control subjects deactivated the posterior cingulate cortex
      (PCC), whereas alcoholic subjects did not. Posterior cingulum fiber integrity
      predicted the degree of PCC deactivation in control but not alcoholic subjects.
      Also, PCC activity was modulated by executive control demands: activated during
      response switching and deactivated during response repetition. Alcoholics showed
      the opposite pattern: activation during repetition and deactivation during
      switching. Here, in alcoholic subjects, greater deviations from the normal PCC
      activity correlated with higher amounts of lifetime alcohol consumption. A
      functional dissociation of brain network connectivity between the groups further
      showed that control subjects exhibited greater corticocortical connectivity among
      middle cingulate, posterior cingulate, and medial prefrontal cortices than
      alcoholic subjects. In contrast, alcoholic subjects exhibited greater midbrain
      orbitofrontal cortical network connectivity than control subjects. Degree of
      microstructural fiber integrity predicted robustness of functional connectivity.
      CONCLUSIONS: Thus, even subtle compromise of microstructural connectivity in
      alcoholism can influence modulation of functional connectivity and underlie
      alcohol-related cognitive impairment.

PMID- 22137509
TI  - Prevalence of New Delhi metallo-beta-lactamase (NDM-1)-positive bacteria in a
      tertiary care centre in Pune, India.

PMID- 22137510
TI  - Standard clinical risk factors for difficult laryngoscopy are not independent
      predictors of intubation success with the GlideScope.
AB  - STUDY OBJECTIVES: To determine whether the first-attempt tracheal intubation
      incidence using the GlideScope videolaryngoscope is higher in patients with
      predicted increased risk of difficult laryngoscopy, and to assess the ability of
      other a priori defined standard risk factors to predict first-attempt intubation
      success, in aggregate and by forming scores. DESIGN: Prospective study. SETTING:
      Operating room in a tertiary-care academic center. PATIENTS: 357 patients
      intubated with the GlideScope for nonemergent general anesthesia. INTERVENTIONS
      AND MEASUREMENTS: Mallampati airway class was used to create two groups of
      patients, one with higher and the other, lower, potential difficult laryngoscopy
      (Mallampati classes 3-4 and 1-2, respectively). Intubation success on the first
      attempt with the GlideScope videolaryngoscope in patients with a Mallampati class
      3 or 4 airway versus those with Mallampati class 1 or 2 airway was tested. We
      also evaluated the predictive ability of the Mallampati airway class (1 and 2 vs
      3 and 4) along with 9 other possible predictors of difficult intubation on first
      attempt intubation success: gender, age, body mass index, level of training
      within our anesthesia residency program (Clinical Anesthesia Resident years 1, 2,
      and 3), ASA physical status, mouth opening, thyromental distance, neck flexion,
      and neck extension. MAIN RESULTS: None of the standard predictors of difficult
      intubation was significantly associated with outcome after adjusting for other
      predictors. A multivariable model containing the aggregate set of variables
      predicted outcome significantly better than a risk score formed as the sum of 10
      predictors ("Risk 10"; P = 0.0176). CONCLUSIONS: With GlideScope-assisted
      tracheal intubation, Mallampati airway class is not an independent risk factor
      for difficult intubation. Other standard clinical risk factors of difficulty with
      direct laryngoscopy also do not appear to be individually predictive of first
      attempt success of tracheal intubation.

PMID- 22137511
TI  - The effect of intravenous tranexamic acid on blood loss and surgical field
      quality during endoscopic sinus surgery: a placebo-controlled clinical trial.
AB  - STUDY OBJECTIVES: To evaluate the effects of intravenous (IV) tranexamic acid on
      blood loss and surgical field quality during functional endoscopic sinus surgery
      (FESS). DESIGN: Randomized, double-blinded, controlled trial. SETTING: Operating
      room and postoperative recovery area of a university-affiliated hospital.
      PATIENTS: 84 consecutive, adult, ASA physical status 1 and 2 patients undergoing
      FESS. INTERVENTIONS: Patients were randomized to receive either IV tranexamic
      acid 10 mg/kg (TA group) or sterile water 0.1 mL/kg (placebo group) as a bolus
      dose immediately after induction of anesthesia. MEASUREMENTS: Amount of blood
      loss and bleeding and satisfaction scores were obtained from the surgeon. MAIN
      RESULTS: Blood loss in the TA group was 184 +/- 64 mL and in the placebo group,
      312 +/- 75 mL on average (P < 0.01). The median (range) bleeding score in the TA
      group was significantly lower than the placebo group [2 (1-3) vs 2.5 (2-4); P <
      0.0001]. The surgeon was more satisfied with the surgical field in the TA group
      than the placebo group [median score: 4 (3-5) vs 3 (1-5), P < 0.001]. CONCLUSION:
      Intravenous tranexamic acid effectively reduces bleeding and improves the
      surgical field during FESS.

PMID- 22137512
TI  - Cardiovasular changes after placement of a classic endotracheal tube, double
      lumen tube, and Laryngeal Mask Airway.
AB  - STUDY OBJECTIVE: To compare hemodynamic responses, P wave dispersion (Pd), and QT
      dispersion (QTd) after placement of a classic endotracheal tube (ETT), double
      lumen tube (DLT), or Laryngeal Mask Airway (LMA). DESIGN: Prospective study.
      SETTING: Outpatient surgery center. PATIENTS: 75 adult, ASA physical status 1 and
      2 patients undergoing cystoscopy and thoracoscopic surgery. INTERVENTIONS:
      Patients were randomized to undergo placement of an ETT (Group T; n = 25), DLT
      (Group D; n = 25), or LMA (Group L; n = 25). Anesthesia was induced by etomidate
      0.3 mg/kg and fentanyl 1.0 MUg/kg, and maintained with nitrous oxide, oxygen, 2%
      to 3% sevoflurane, and rocuronium 0.5 mg/kg. MEASUREMENTS: Mean arterial pressure
      (MAP) and heart rate (HR) were recorded immediately before intubation and after
      intubation at one, 3, 5, 10,15, 20, 25, and 30 minutes after intubation/airway
      insertion. RESULTS: QT dispersion after tube placement was significantly higher
      than before tube placement in Group D (P = 0.0001) and Group L (P = 0.03). Mean
      arterial pressure and HR in Group T were significantly higher than in Group L at
      the first minute after tube placement (P = 0.02). Heart rate and MAP at baseline
      were significantly higher than the other measurement times in Groups T and D (P <
      0.01). CONCLUSIONS: The LMA caused no change in Pd, HR, or MAP values during or
      after airway placement, but caused QTd after airway insertion. The ETT caused a
      sudden increase at the first minute after tube placement, without any Pd or QTd.
      In addition, DLT caused QTd without any serious change in hemodynamics.

PMID- 22137513
TI  - Anesthesia management of totally endoscopic atrial septal defect repair with a
      robotic surgical system.
AB  - STUDY OBJECTIVE: To investigate anesthetic techniques for robot-assisted
      endoscopic atrial septal defect (ASD) repair. DESIGN: Clinical observational
      study. SETTING: Operating room of a general military hospital. PATIENTS: 56
      adult, ASA physical status 1 and 2 patients undergoing elective general
      anesthesia. INTERVENTIONS: After induction of general anesthesia, a left-sided,
      double-lumen endotracheal tube was positioned to allow single left-lung
      ventilation and contralateral CO(2) pneumothorax (capnothorax). With ultrasound
      guidance, peripheral cardiopulmonary bypass (CPB) catheters were placed.
      MEASUREMENTS AND MAIN RESULTS: All patients tolerated single left-lung
      ventilation before CPB; however, hypoxia (oxygen saturation < 90%) occurred in 11
      (19.6%) patients post-CPB, which required treatment with continuous positive
      airway pressure. Fifteen (26.8%) patients had hypotension secondary to
      capnothorax, which was treated with transfusion and vasopressors. Aortic cross
      clamp time was 43.6 +/- 11.2 minutes, and CPB time was 106.7 +/- 12.4 minutes.
      The median intensive care unit stay was 21 hours and postoperative hospital stay
      was 4 to 7 days. CONCLUSIONS: The key issue for anesthetic management of robot
      assisted totally endoscopic ASD repair is maintaining stable hemodynamics and
      oxygenation, especially during one-lung ventilation and capnothorax.

PMID- 22137514
TI  - The effect of stimulating versus conventional perineural catheters on
      postoperative analgesia following ultrasound-guided femoral nerve localization.
AB  - STUDY OBJECTIVE: To test the hypothesis that, if the femoral nerve is correctly
      localized using ultrasound (US) guidance, the type of perineural catheter used
      has no effect on catheter success. DESIGN: Randomized controlled trial. SETTING:
      Post-anesthesia care unit of an academic teaching hospital. PATIENTS: 40 ASA
      physical status 1, 2, and 3 patients, ages 55-85 years, undergoing elective total
      knee arthroplasty. INTERVENTIONS: All patients received postoperative continuous
      femoral nerve blocks and a single injection sciatic nerve block. Nerve
      localization was accomplished using US guidance and electrical nerve stimulation
      so that the needle tip was visualized deep to the femoral nerve. Patients were
      randomized to receive either stimulating (Group SC) or nonstimulating catheters
      (Group NSC) in the usual manner for each device. Catheters were bolused with
      ropivacaine and an infusion commenced. MEASUREMENTS: The primary outcome was
      quality of analgesia (as measured by a numerical rating scale). Other outcomes
      included sensory block success rate, number of attempts and time required to
      localize the needle tip correctly, number of attempts and time required to place
      the perineural catheter, amount of local anesthetic and opioid use
      postoperatively, and degree of completion of preset postoperative rehabilitation
      goals. MAIN RESULTS: Quality of analgesia was similar at all time intervals.
      Rates of successful femoral block (95% vs 80%; P = 0.34) were similar between
      groups. Time required to position the catheter was greater in Group SC than Group
      NSC (3.45 +/- 2.05 min vs 1.72 +/- 0.88 min; P < 0.01). CONCLUSIONS: Ultrasound
      guidance for needle localization prior to catheter insertion for femoral nerve
      block results in similar block characteristics between stimulating and
      nonstimulating catheters. The use of nonstimulating catheters avoids the
      technical challenges of stimulating catheters and does not require additional
      helpers.

PMID- 22137515
TI  - Cost-effectiveness analysis of flexible optical scopes for tracheal intubation: a
      descriptive comparative study of reusable and single-use scopes.
AB  - STUDY OBJECTIVE: To calculate the costs per intubation of reusable fiberoptic
      scopes versus single-use intubation scopes. DESIGN: Open-label retrospective
      study. SETTING: University-affiliated hospital. MEASUREMENTS: The one-year
      intubation records of intubations performed with reusable intubation scopes, the
      one-year maintenance costs of these scopes, and their three-year repair cost
      records were analyzed. A total of 166 intubations were performed with reusable
      fiberoptic scopes in 2009. Calculations to assess the costs per intubation based
      on the documented records at our institution were made. The total cost of an
      intubation, the repair-to-intubation ratio, and the repair cost per intubation
      were determined. MAIN RESULTS: The total cost of an intubation at our institution
      in 2009, using reusable scopes, was $119.75 [US dollars (USD)], which included
      $20.15 (purchasing), $53.48 (repair), $33.16 (maintenance), and $12.96 (labor).
      The repair-to-intubation ratio was 1:55. Repair costs were $53.48 per intubation
      and $2,959.44 per instance of repair. CONCLUSIONS: The Ambu aScope, a single-use
      intubation scope, is a new addition to video laryngoscopy. The price should range
      within 10% of our intubation cost ($120.00 to $132.00 per single-use intubation
      scope).

PMID- 22137516
TI  - Dental sedation for patients with intellectual disability: a prospective study of
      manual control versus Bispectral Index-guided target-controlled infusion of
      propofol.
AB  - STUDY OBJECTIVE: To investigate the use of propofol sedation using Bispectral
      Index (BIS)-guided target-controlled infusion (TCI) in dental patients with
      intellectual disability. DESIGN: Single-center, prospective, randomized clinical
      trial. SETTING: Academic outpatient clinic. SUBJECTS: 40 ASA physical status 1
      and 2 patients with intellectual disability. INTERVENTIONS: Patients were
      randomized to two groups. The manual control (MC) group (n = 20) had sedation by
      manually controlled infusion of propofol without a BIS index monitor. The BIS-TCI
      group (n = 20) had sedation by BIS-guided TCI of propofol. MEASUREMENTS: The
      required dose of propofol, recovery time for the eyelash reflex, and spontaneous
      eye opening times were recorded. MAIN RESULTS: BIS-TCI significantly reduced the
      dose of propofol and shortened the recovery times for eyelash reflex and
      spontaneous eye opening. CONCLUSION: Propofol sedation using BIS-guided TCI is a
      useful and safe method in the management of patients with intellectual
      disability.

PMID- 22137517
TI  - Anesthetic management of tracheoesophageal fistula repair in a newborn with a
      double-outlet right ventricle.
AB  - A case of a newborn with a double-outlet right ventricle and tracheoesophageal
      fistula is presented. The pathophysiology of double-outlet right ventricle and
      its anesthetic implications for tracheoesophageal fistula repair are discussed.

PMID- 22137518
TI  - Dexmedetomidine controls twitch-convulsive syndrome in the course of uremic
      encephalopathy.
AB  - An 85 year old man with a history of chronic renal insufficiency was admitted to
      the cardiothoracic intensive care unit after aortic valve replacement. His
      postoperative course was marked by acute oliguric renal failure for high blood
      urea nitrogen (BUN) and acute hyperactive delirium. At this time he also
      developed tremors with muscle twitching; he received no other form of sedatives.
      A neurology consult made the diagnosis of twitch-convulsive syndrome associated
      with uremic encephalopathy. While the patient was receiving the dexmedetomidine
      infusion, the signs of the twitch-convulsive syndrome, particularly the twitching
      and tremors, disappeared. Within 30 minutes of the end of the dexmedetomidine
      infusion, symptoms of the twitch-convulsive syndrome returned, manifesting as
      acute tremulousness. After several dialysis treatments, his BUN decreased and the
      dexmedetomidine was weaned, without return of the symptoms of twitch-convulsive
      syndrome.

PMID- 22137519
TI  - Severe intraoperative hyponatremia associated with the absorption of irrigation
      fluid during hysteroscopic myomectomy: a case report.
AB  - A case of severe hyponatremia with accompanying pulmonary edema and
      cardiovascular instability during a hysteroscopic myomectomy with general
      anesthesia is presented. The patient's sodium value decreased to 87 mmol/L. She
      was managed with aggressive maneuvers, including an infusion of 3% hypertonic
      saline. The patient's serum sodium increased to 113 mmol/L at the end of the
      operation, and it was increased up to 138 mmol/L at 48 hours. The patient
      recovered completely without neurologic sequelae.

PMID- 22137520
TI  - Cesarean delivery in a parturient with syringomyelia and worsening neurological
      symptoms.
AB  - A parturient presented at 35 weeks' gestation with worsening neurological
      symptoms caused by syringomyelia. She underwent urgent cesarean delivery. The
      etiology and anesthetic considerations for an obstetrical patient with
      syringomyelia are discussed.

PMID- 22137521
TI  - Potential adverse effects of norepinephrine on cortical somatosensory-evoked
      potentials during carotid endarterectomy: a case report.
AB  - The cerebral metabolic and vascular effects of intravenous norepinephrine have
      been shown in an animal model using somatosensory-evoked potentials (SSEPs). A
      case of intravenous norepinephrine resulting in a decrease in SSEP amplitude (of
      greater than 50%) despite no significant change in blood pressure, prior to cross
      clamping during a carotid endarterectomy is presented. This finding may have
      implications for the use of norepinephrine in the critical care unit as well as
      the operating room.

PMID- 22137522
TI  - Peripartum acute coronary syndrome in an otherwise healthy patient.
AB  - Myocardial ischemia in pregnancy poses a significant challenge for the
      anesthesiologist. It is a relatively rare disorder (approximately 180 cases
      published in the indexed literature since 1922) but it carries high mortality.
      Diagnosis is frequently hampered by diminished sensitivity of several testing
      modalities conventionally used to diagnose myocardial ischemia. The etiology of
      cardiac ischemia also is multifactorial and occurs during a very dynamic period.
      A case of acute coronary syndrome in a parturient during urgent cesarean delivery
      for placental abruption is presented, followed by a brief review of the topic.

PMID- 22137523
TI  - High cuff pressure in the silicone endotracheal tube of the LMA-Fastrach:
      implications for patient safety.

PMID- 22137524
TI  - The nasotracheal Airtraq laryngoscope also may be useful for orotracheal
      intubation in anesthetized patients.

PMID- 22137525
TI  - Perioperative management of a patient with a massive lipomatous mediastinal mass,
      severe cardiomyopathy, and tracheal stenosis for urgent laser bronchoscopy and
      stent placement.

PMID- 22137526
TI  - Transient urinary incontinence after sciatic nerve block with the classic Labat
      approach.

PMID- 22137527
TI  - Recovery room waitlists may be predicted.

PMID- 22137528
TI  - A novel airway monitor for the nonsecured airway during magnetic resonance
      imaging in children.

PMID- 22137529
TI  - Prolonged neuromuscular block after an accidental epidural injection of
      vecuronium.

PMID- 22137530
TI  - Anesthetic management of Pallister-Killian syndrome using a Bispectral Index
      monitor in a patient with severe seizures.

PMID- 22137531
TI  - Morphine to codeine concentration ratio in blood and urine as a marker of illicit
      heroin use in forensic autopsy samples.
AB  - A morphine to codeine ratio greater than unity (M/C>1) has been suggested as an
      indicator of heroin use in living individuals. The aim of this study was to
      examine the morphine to codeine ratio in a large population (N=2438) of
      forensically examined autopsy cases positive for 6-monoacetylmorphine (6-MAM)
      and/or morphine in blood and/or urine. Blood and urine concentrations of 6-MAM,
      morphine and codeine were examined using GC-MS and LC-MS/MS methods. In 6-MAM
      positive samples, the M/C ratio was greater than unity in 98% (N=917) of the
      blood samples and 96% (N=665) of the urine samples. Stratification of 6-MAM
      negative cases by M/C above or below unity revealed similarities in morphine and
      codeine concentrations in cases where M/C>1 and 6-MAM positive cases. Median
      blood and urine morphine concentrations were 8-10 times greater than codeine for
      both groups. Similarly to 6-MAM positive cases, 25-44 year-old men prevailed in
      the M/C>1 group. In comparison to cases where M/C <= 1, the M/C ratio was a
      hundred times higher in both 6-MAM positive and M/C>1 cases. The range of
      morphine concentration between the lowest and the highest quintile of codeine in
      M/C>1 cases was similar to that in 6-MAM positive cases. This range was much
      higher than for M/C <= 1 cases. Moreover, linear regression analyses, adjusted
      for age and gender, revealed a strong positive association between morphine and
      codeine in 6-MAM positive and M/C>1 cases. The M/C ratio appeared to be a good
      marker of heroin use in post-mortem cases. Both blood and urine M/C>1 can be used
      to separate heroin users from other cases positive for morphine and codeine.

PMID- 22137532
TI  - Severe, long-term hypoglycemia induced by co-trimoxazole in a patient with
      predisposing factors.

PMID- 22137533
TI  - Obesity and postprandial lipemia in adolescents: risk factors for cardiovascular
      disease.
AB  - In the last 50 years, obesity has become a global epidemic and is one of the main
      public health problems in many parts of the world. Adolescence is a critical
      period regarding weight control. The factors determining obesity include a
      complex group of interrelated biological, behavioral and environmental factors
      which reinforce each other. In children and adolescents, obesity is associated
      with premature cardiovascular diseases, diabetes mellitus type 2, acanthosis
      nigricans, respiratory and skeletal muscle problems, as well as psychological
      problems. The clinical manifestations of cardiovascular disease begin in middle
      age. Nevertheless, studies indicate that the atherosclerotic process begins to
      develop during childhood. Postprandial hyperlipemia is a physiological process
      that occurs several times a day after the complete absorption of a diet including
      lipids and has been suggested as a risk factor for coronary heart disease (CHD).
      New study areas include the effects of different fatty acids, lipid sources
      (endogenous and exogenous), and the effect ingesting alcoholic beverages during
      meals. Given the evidence that postprandial lipidemia is an independent risk
      factor for CHD, it is vital to establish normative values for children and
      adolescents such that more effective and efficient preventive and therapeutic
      measures can be adopted.

PMID- 22137534
TI  - Growth-dependent effects of dietary protein concentration and quality on the
      biomechanical properties of the diaphyseal rat femur.
AB  - OBJECTIVES: This study compares the effects of feeding growing rats with
      increasing concentrations of casein (C) and wheat gluten (G), proteins that show
      different biological qualities, on the morphometrical and biomechanical
      properties of the femoral diaphysis. MATERIALS AND METHODS: Female rats were fed
      with one of ten diets containing different concentrations (5-30%) of C and G
      between the 30th and 90th days of life (Control=C-20%). Biomechanical structural
      properties of the right femur middiaphysis were estimated using a 3-point bending
      mechanical test with calculation of some indicators of bone material properties.
      RESULTS: Body weight and length were affected by treatments, values being highest
      in rats fed the C-20% diet. G diets affected negatively both parameters. Changes
      in cross-sectional geometry (mid-diaphyseal cross-sectional and cortical areas,
      femoral volume, and rectangular moment of inertia) were positively related to the
      C content of the diet, while they were severely and negatively affected by G
      diets. Similar behaviors were observed in the bone structural properties
      (fracture load, yielding load, diaphyseal stiffness and elastic energy
      absorption). When values of strength and stiffness were normalized for body
      weight, the differences disappeared. The bone material quality indicators
      (elastic modulus, yielding stress, elastic energy absorption/volume) did not
      differ significantly among all studied groups. Femoral calcium concentration in
      ashes was not significantly different among groups. CONCLUSION: The clear
      differences in strength and stiffness of bone beams induced by dietary protein
      concentration and quality seemed to be the result of an induced subnormal gain in
      bone structural properties as a consequence of a correlative subnormal gain in
      bone growth and mass, yet not in bone material properties.

PMID- 22137535
TI  - Dengue in the Middle East: a neglected, emerging disease of importance.
AB  - Dengue transmission has increased worldwide, particularly in Asia and Latin
      America since the 1970s, but limited information on the disease is available from
      the Middle East. Saudi Arabia and Yemen have reported a few epidemics of dengue.
      Three of the four dengue virus serotypes (DENV-1-3) have been reported in the
      region. Climate conditions in the Middle East are not favourable for the disease
      vector, but all other risk factors for dengue are potentially increasing. The
      existence of a large immigrant work force from dengue-endemic countries,
      increased travel from and to dengue-endemic countries and increased urbanization
      are expected to increase the likelihood of the emergence of dengue in the Middle
      East.

PMID- 22137536
TI  - In vitro growth kinetics, differentiation and morphological characterisation of
      Tunisian Leishmania infantum parasites.
AB  - In this study, a negative peanut agglutinin (PNA) selection was used as a marker
      for promastigote differentiation to compare the in vitro growth and
      differentiation kinetics of two visceral and two cutaneous Leishmania
      (Leishmania) infantum parasites. All parasites had different growth and
      differentiation kinetics. Cultures initiated with PNA(+) parasites purified
      during the early stationary phase (Day 4), when PNA(-) (non-agglutinating)
      parasites peaked, yielded a high PNA(-) percent. Further morphological analysis
      at this time point showed that 60-86% of PNA(+) forms were procyclics, whilst
      PNA(-) forms were composed of 53-71% leptomonads. Nectomonads were present both
      in PNA(-) and PNA(+) promastigote fractions at nearly equivalent proportions,
      suggesting that they constitute a transition state in the Leishmania development
      process, with a fraction of them sharing common constituents of the surface coat
      with procyclics and the other with leptomonads. Obtaining a high density of
      promastigotes undergoing developmental differentiation may be useful for further
      molecular and biochemical identification of developmental stage-specific markers.

PMID- 22137537
TI  - The decline of typhoid and the rise of non-typhoid salmonellae and fungal
      infections in a changing HIV landscape: bloodstream infection trends over 15
      years in southern Vietnam.
AB  - The etiological spectrum of bloodstream infections is variable between
      industrialized and developing countries and even within a defined location over
      time. We investigated trends in bloodstream infections at an infectious disease
      hospital in Ho Chi Minh City, Vietnam, from 1994-2008. Amongst 66,111 blood
      cultures performed, a clinically relevant pathogen was isolated in 7645 episodes
      (positivity rate; 116/1000 cultures). Salmonella Typhi was the predominant
      pathogen until 2002; however, a considerable annual decline in the proportion of
      S. Typhi was observed (OR 0.6993, 95% CI [0.6885, 0.7103], p<0.0001). Conversely,
      there was a significant increase in the proportions of non-typhoidal Salmonella
      (NTS), Cryptococcus neoformans and Penicillium marneffei, concurrent with
      increasing HIV prevalence. These data document a substantial longitudinal shift
      in bloodstream infection etiology in southern Vietnam. We propose such changes
      are related to increasing economic prosperity and HIV prevalence, and this
      pattern marks a substantial change in the epidemiology of invasive salmonellosis
      in Southeast Asia.

PMID- 22137538
TI  - Evaluation of a novel chromatographic immunoassay based on Dual-Path Platform
      technology (DPP(r) CVL rapid test) for the serodiagnosis of canine visceral
      leishmaniasis.
AB  - Canine visceral leishmaniasis (CVL) is the major source of human visceral
      leishmaniasis (VL) and is transmitted from dogs to sand flies to humans. To
      control the spread of this disease, early and accurate detection of infected dogs
      is critical but challenging. Here we demonstrate the potential of the Dual-Path
      Platform (DPP((r))) CVL rapid test for detecting K26/K39-reactive antibodies in
      sera from clinically symptomatic (n=60) and asymptomatic (n=60) Leishmania
      infantum-infected dogs. For the specificity evaluation, assays were performed
      using known negative diagnostic serum samples (n=59) and cross-reaction control
      sera (n=11) from animals born in a VL-free area of Brazil. The diagnostic kit
      displayed high specificity (96%) but low sensitivity (47%) in identifying
      parasite-positive dogs without signs of CVL. However, the test sensitivity was
      significantly higher (98%) in diseased cases, indicating that this convenient
      test may be useful to identify the most infectious dogs. Efforts should be
      pursued to obtain a more sensitive DPP-multiplexed test parameter (i.e. based on
      simultaneous yet separate antibody detection of carefully selected multiple
      antigens of diagnostic utility) for effective serodiagnosis of early-infected
      dogs, as this will likely allow more efficient canine removal regimens than those
      used in practice by public health services.

PMID- 22137539
TI  - Detection of parvovirus B19 capsid proteins in testicular tissues.
AB  - OBJECTIVE: To detect B19 capsid proteins, VP1 and VP2, in testicular tissues,
      both normal and tumor, using immunohistochemistry. METHODS: Samples of normal,
      fetal, and tumor testicular tissue (n = 31) and normal testicular DNA (n = 1)
      were tested for the presence of B19. Immunohistochemistry staining was used for
      the detection of viral capsid proteins VP1 and VP2. Polymerase chain reaction
      with 4 primer sets was used to test for the presence of B19 DNA in a normal
      testicular sample. RESULTS: B19 capsid protein VP1 and VP2 was detected by
      immunohistochemistry in 6 (85.7%) of 7 normal testicular samples and 17 (73.9%)
      of 23 tumor samples. The findings from a normal fetal testicular sample were
      equivocal. B19 DNA was detected in normal testicular DNA with 4 of the 4 primer
      sets used. CONCLUSION: In contrast to previous reports, B19 capsid proteins VP1
      and VP2 have now been detected in both normal and tumor testicular tissue. The
      persistence of B19 in a diverse range of tissues, including the testes, requires
      more research into the molecular mechanisms by which B19 can enter these cells,
      as well as the possible etiologic roles in chronic diseases, including cancer.

PMID- 22137540
TI  - Monitoring validated quality of life outcomes after prostatectomy: initial
      description of novel online questionnaire.
AB  - OBJECTIVES: To describe a novel, low-cost, online health-related quality of life
      (HRQOL) survey that allows for automated follow-up and convenient access for
      patients in geographically diverse locations. Clinicians and investigators have
      been encouraged to use validated HRQOL instruments when reporting outcomes after
      radical prostatectomy. METHODS: The institutional review board approved our
      protocol and the use of a secure web site (http://www.SurveyMonkey.com) to send
      patients a collection of validated postprostatectomy HRQOL instruments by
      electronic mail. To assess compliance with the electronic mail format, a pilot
      study of cross-sectional surveys was sent to patients who presented for follow-up
      after robotic-assisted laparoscopic prostatectomy. The response data were
      transmitted in secure fashion in compliance with the Health Insurance Portability
      and Accountability Act. RESULTS: After providing written informed consent, 514
      patients who presented for follow-up after robotic-assisted laparoscopic
      prostatectomy from March 2010 to February 2011 were sent the online survey. A
      total of 293 patients (57%) responded, with an average age of 60 years and a
      median interval from surgery of 12 months. Of the respondents, 75% completed the
      survey within 4 days of receiving the electronic mail, with a median completion
      time of 15 minutes. The total survey administration costs were limited to the web
      site's $200 annual fee-for-service. CONCLUSIONS: An online survey can be a low
      cost, efficient, and confidential modality for assessing validated HRQOL outcomes
      in patients who undergo treatment of localized prostate cancer. This method could
      be especially useful for those who cannot return for follow-up because of
      geographic reasons.

PMID- 22137541
TI  - Efficacy of neuroselective and site-specific nociceptive stimuli of rat bladder.
AB  - OBJECTIVE: To evaluate the organ specificity of sine wave electrical stimulation
      of the bladder through assessment of the expression of Fos-immunoreactive (IR)
      cells in rat spinal cord regions. METHODS: A total of 37 female Sprague-Dawley
      rats were divided into 8 groups: sham stimulation; 5, 250, and 2000 Hz
      stimulation with 1.5- or 2.0-mA intensity; and a group instilled with capsaicin
      in the bladder. Using a recently developed bladder sensory threshold device, sine
      wave electrical stimulation was applied for 90 minutes to the rat bladder. The
      spinal cord was harvested after the rats were killed. The Fos-IR cells in the
      spinal regions of the medial dorsal horn, lateral dorsal horn, dorsal commissure,
      and sacral parasympathetic nucleus were measured. The distributions of the Fos-IR
      neurons were compared. RESULTS: The maximal expression of Fos-IR cells, induced
      by 250- and 5-Hz stimulation of the bladder, was found at L6 of the spinal cord
      and was significantly greater than that in the control group (P<.01). Stimulation
      with 2000 Hz did not induce any Fos-IR cells. Fos-IR neurons were predominantly
      seen in the sacral parasympathetic nucleus region in response to 250-Hz
      stimulation and in the dorsal commissure region in response to 5-Hz stimulation.
      The number of positive neurons was similar to the number caused by capsaicin
      instillation. CONCLUSION: Frequency-specific sine wave electrical stimulation of
      the rat bladder induced the expression of Fos-IR cells in a neuroselective
      manner. The bladder sensory threshold device could be used for exploration of the
      pathophysiology of diseases with disturbances of the afferent pathway of the
      bladder.

PMID- 22137542
TI  - High classification of chronic heart failure increases risk of overactive bladder
      syndrome and lower urinary tract symptoms.
AB  - OBJECTIVE: To assess the urologic symptoms among patients with chronic heart
      failure (CHF) and to explore whether a higher classification of CHF increases the
      risk associated with overactive bladder syndrome (OAB) and lower urinary tract
      symptoms. METHODS: A total of 214 ambulatory patients with CHF (129 men and 85
      women) and 378 age-matched subjects (222 men and 156 women) were enrolled in the
      present study. The urologic symptoms were evaluated using the Overactive Bladder
      Symptom Score (OABSS) and International Prostate Symptom Score (IPSS) from
      January to June 2010. RESULTS: Compared with the controls, the patients with CHF
      had a significantly greater mean OABSS (4.6+/-3.6 vs 3.4+/-3.1, P<.001), total
      IPSS (8.3+/-6.9 vs 6.9+/-7.6, P=.021), and storage IPSS (4.8+/-3.5 vs 3.7+/-3.3,
      P<.001). Of the patients with CHF, 34.1% had moderate/severe OAB symptoms
      (OABSS>=6), and 43.5% had moderate/severe lower urinary tract symptoms (IPSS>=8).
      Compared with patients who had New York Heart Association (NYHA) class I CHF, the
      patients with NYHA class III CHF had a significantly greater OABSS and total,
      storage, and voiding IPSSs. Patients with NYHA class II CHF did not. A greater
      body mass index and stroke were significantly associated with the OABSS and
      storage IPSS, and pulmonary disease was significantly associated with the voiding
      IPSS. CONCLUSION: The patients with CHF had more storage urinary symptoms
      suggestive of OAB than did the age-matched controls. Among the patients with CHF,
      greater NYHA class heart function was significantly associated with OAB and lower
      urinary tract symptoms.

PMID- 22137543
TI  - Intravesical chondroitin sulfate inhibits recruitment of inflammatory cells in an
      acute acid damage "leaky bladder" model of cystitis.
AB  - OBJECTIVE: To investigate whether a physiologic effect of "glycosaminoglycan
      (GAG) replenishment therapy" altered recruitment of inflammatory cells in an
      acute bladder damage model. Replacement of the GAG layer with intravesically
      administered GAGs is an effective therapy for interstitial cystitis in at least
      some patients. Intravesically administered chondroitin sulfate was previously
      shown to bind to and restore the impermeability of surface-damaged ("leaky")
      urothelium to small ions. METHODS: Rat bladders were damaged with 10 mM HCl.
      Negative control bladders were treated with phosphate-buffered saline. On the
      following day, the animal bladders were treated with 20 mg/mL chondroitin sulfate
      in phosphate-buffered saline, and the negative and positive controls were treated
      with phosphate-buffered saline alone. At 2 and 4 days after treatment with
      chondroitin sulfate, the rats were killed, and sections of their bladders were
      analyzed using toluidine blue staining for mast cell immunohistochemical labeling
      using antibodies against CD45 for lymphocytes and myeloperoxidase for
      neutrophils. RESULTS: Chondroitin sulfate treatment reduced the recruitment, in a
      statistically significant manner, of inflammatory cells, including neutrophils
      and mast cells to the suburothelial space but did not alter recruitment of CD45
      positive lymphocytes. CONCLUSION: For the first time, we have demonstrated that
      intravesical GAG replenishment therapy also produces a physiologic effect of
      decreasing recruitment of inflammatory cells in an acute model of the damaged
      bladder. These findings support the use of intravesically administered GAG for
      bladder disorders that result from a loss of impermeability, including
      interstitial, radiation, and chemical cystitis, and possibly others as well.

PMID- 22137544
TI  - Correlations among cardiovascular risk factors, prostate blood flow, and prostate
      volume in patients with clinical benign prostatic hyperplasia.
AB  - OBJECTIVE: To investigate the relationships among the cardiovascular risk
      factors, prostate blood flow, and prostate volume in patients with clinical
      benign prostatic hyperplasia (BPH). METHODS: A total of 130 patients with the
      clinical diagnosis of BPH were recruited. The presence of 5 cardiovascular risk
      factors, including obesity, diabetes, hypertension, hyperlipidemia, and a history
      of cardiovascular events, was recorded. The urologic evaluation included digital
      rectal examination, serum prostate-specific antigen, International Prostate
      Symptom Score, and transrectal ultrasonography. Doppler spectrum analysis was
      performed with the patient in the right lateral decubitus position to measure the
      blood flow in the prostate capsular arteries, periurethral arteries, and
      neurovascular bundles. The correlations were analyzed between the resistive
      indexes of the prostatic branches and the cardiovascular risk factors, as well as
      the transrectal ultrasound findings. RESULTS: The resistive indexes of the
      periurethral arteries and right neurovascular bundles showed positive
      correlations with the number of cardiovascular risk factors in the patients
      (r=.228, P=.01 and r=.225, P=.011, respectively). The periurethral artery
      resistive index also correlated positively with both prostate and transitional
      zone volumes, with the capsular artery correlating positively only with the
      latter. No significant correlations were noted between the resistive indexes and
      the International Prostate Symptom Score. CONCLUSION: Prostate vascular
      resistance in patients with BPH has positive correlations with cardiovascular
      risk factors and prostate size. These findings suggest that prostate hypoxia
      might play a role in the pathogenesis of BPH.

PMID- 22137545
TI  - Temporal diffeomorphic free-form deformation: application to motion and strain
      estimation from 3D echocardiography.
AB  - This paper presents a new registration algorithm, called Temporal Diffeomorphic
      Free Form Deformation (TDFFD), and its application to motion and strain
      quantification from a sequence of 3D ultrasound (US) images. The originality of
      our approach resides in enforcing time consistency by representing the 4D
      velocity field as the sum of continuous spatiotemporal B-Spline kernels. The
      spatiotemporal displacement field is then recovered through forward Eulerian
      integration of the non-stationary velocity field. The strain tensor is computed
      locally using the spatial derivatives of the reconstructed displacement field.
      The energy functional considered in this paper weighs two terms: the image
      similarity and a regularization term. The image similarity metric is the sum of
      squared differences between the intensities of each frame and a reference one.
      Any frame in the sequence can be chosen as reference. The regularization term is
      based on the incompressibility of myocardial tissue. TDFFD was compared to
      pairwise 3D FFD and 3D+t FFD, both on displacement and velocity fields, on a set
      of synthetic 3D US images with different noise levels. TDFFD showed increased
      robustness to noise compared to these two state-of-the-art algorithms. TDFFD also
      proved to be more resistant to a reduced temporal resolution when decimating this
      synthetic sequence. Finally, this synthetic dataset was used to determine optimal
      settings of the TDFFD algorithm. Subsequently, TDFFD was applied to a database of
      cardiac 3D US images of the left ventricle acquired from 9 healthy volunteers and
      13 patients treated by Cardiac Resynchronization Therapy (CRT). On healthy cases,
      uniform strain patterns were observed over all myocardial segments, as
      physiologically expected. On all CRT patients, the improvement in synchrony of
      regional longitudinal strain correlated with CRT clinical outcome as quantified
      by the reduction of end-systolic left ventricular volume at follow-up (6 and
      12months), showing the potential of the proposed algorithm for the assessment of
      CRT.

PMID- 22137547
TI  - Variations in young men's and women's attitudes and intentions to use condoms
      with different types of sexual partners.

PMID- 22137546
TI  - Grappling with HIV transmission risks: narratives of rural women in eastern Kenya
      living with HIV.
AB  - As people live longer and more productively with HIV infection, issues of agency
      in reducing HIV risk are particularly important for HIV-infected women living in
      high prevalence, underresourced countries such as Kenya. Because of their
      gendered lives, in that being masculine is associated with dominance and being
      feminine is associated with passiveness, women in rural Kenya must cope with
      continued HIV transmission risk even after knowing they are infected with HIV. In
      this narrative interview study, informed by theories of gender and postcolonial
      feminism, we examined personal accounts of HIV risk and risk reduction of 20
      rural women in eastern Kenya who were living with HIV. From our analysis of the
      women's narratives, two major themes emerged: gender-based obstacles even in the
      context of a known HIV diagnosis, and struggles with economic pressures amid HIV
      risks. Implications for policy, programs, and research are discussed.

PMID- 22137548
TI  - Pilot study to assess subjective and objective reporting of potential adverse
      drug reactions in older versus younger HIV-infected patients using antiretroviral
      therapy.
AB  - Limited data exist on tolerability of antiretroviral therapy (ART) in older HIV
      infected patients compared to their younger counterparts. There is also concern
      for overlap of ART toxicities with concomitant conditions potentially leading to
      an increased burden of ART-related adverse drug reactions (ADRs). A prospective,
      descriptive-comparative study was conducted to compare incidence and severity of
      ADRs secondary to ART in older (>= 50 years) versus younger (<50 years) HIV
      infected patients. No differences were found in the presence or severity of
      subjective or objective ADRs between groups. The burden of intolerance appeared
      to be high for certain ADRs in both age groups. Regardless of age, subjects with
      certain concomitant illnesses had higher rates of potential ADRs. Providers need
      to be aware of patient characteristics that lead to increased rates of ART
      intolerance; for patients with an increased comorbidity burden, providers need to
      be attentive to the potential impact on ART tolerability.

PMID- 22137550
TI  - A simple control policy for achieving minimum jerk trajectories.
AB  - Point-to-point fast hand movements, often referred to as ballistic movements, are
      a class of movements characterized by straight paths and bell-shaped velocity
      profiles. In this paper we propose a bang-bang optimal control policy that can
      achieve such movements. This optimal control policy is accomplished by minimizing
      the Linfinity norm of the jerk profile of ballistic movements with known initial
      position, final position, and duration of movement. We compare the results of
      this control policy with human motion data recorded with a manipulandum. We
      propose that such bang-bang control policies are inherently simple for the
      central nervous system to implement and also minimize wear and tear on the bio
      mechanical system. Physiological experiments support the possibility that some
      parts of the central nervous system use bang-bang control policies. Furthermore,
      while many computational neural models of movement control have used a bang-bang
      control policy without justification, our study shows that the use of such
      policies is not only convenient, but optimal.

PMID- 22137549
TI  - Two patients with hepatic mtDNA depletion syndromes and marked elevations of S
      adenosylmethionine and methionine.
AB  - This paper reports studies of two patients proven by a variety of studies to have
      mitochondrial depletion syndromes due to mutations in either their MPV17 or DGUOK
      genes. Each was initially investigated metabolically because of plasma methionine
      concentrations as high as 15-21-fold above the upper limit of the reference
      range, then found also to have plasma levels of S-adenosylmethionine (AdoMet) 4.4
      8.6-fold above the upper limit of the reference range. Assays of S
      adenosylhomocysteine, total homocysteine, cystathionine, sarcosine, and other
      relevant metabolites and studies of their gene encoding glycine N
      methyltransferase produced evidence suggesting they had none of the known causes
      of elevated methionine with or without elevated AdoMet. Patient 1 grew slowly and
      intermittently, but was cognitively normal. At age 7 years he was found to have
      hepatocellular carcinoma, underwent a liver transplant and died of progressive
      liver and renal failure at age almost 9 years. Patient 2 had a clinical course
      typical of DGUOK deficiency and died at age 8 1/2 months. Although each patient
      had liver abnormalities, evidence is presented that such abnormalities are very
      unlikely to explain their elevations of AdoMet or the extent of their
      hypermethioninemias. A working hypothesis is presented suggesting that with
      mitochondrial depletion the normal usage of AdoMet by mitochondria is impaired,
      AdoMet accumulates in the cytoplasm of affected cells poor in glycine N
      methyltransferase activity, the accumulated AdoMet causes methionine to
      accumulate by inhibiting activity of methionine adenosyltransferase II, and that
      both AdoMet and methionine consequently leak abnormally into the plasma.

PMID- 22137551
TI  - Clinical failures associated with rpoB mutations in phenotypically occult
      multidrug-resistant Mycobacterium tuberculosis.
AB  - SETTING: Recently, Mycobacterium tuberculosis isolates have been described that
      test phenotypically susceptible to rifampicin (RMP) yet harbour genotypic rpoB
      mutations. OBJECTIVE: 1) To investigate the impact of such mutations on clinical
      outcomes among RMP-susceptible isolates, and 2) to determine the prevalence of
      rpoB mutations among isoniazid (INH) monoresistant isolates at our laboratory and
      to describe the association between the presence of these mutations and clinical
      outcomes. METHODS: M. tuberculosis isolates were screened for mutations in the
      rpoB gene using the Cepheid Gene-Xpert(r) MTB/RIF assay. Clinical correlation was
      made by reviewing patient case notes. RESULTS: Isolates from 94 patients were
      found to have INH-resistant, RMP-susceptible profiles. Clinical information was
      available for 52 patients, including three whose isolates had rpoB mutations. All
      three of these patients had treatment failures, compared to two of 49 patients
      whose isolates did not have rpoB mutations (P = 0.0005). DISCUSSION: We
      demonstrate a significant association between the presence of rpoB gene mutations
      that are not detected at the current RMP critical concentration and treatment
      failure. We suggest that a review of the current RMP critical concentration is
      warranted to ensure that RMP is not used inappropriately for the treatment of
      phenotypically occult multidrug-resistant tuberculosis.

PMID- 22137552
TI  - Intravitreal ganciclovir maintenance injection for cytomegalovirus retinitis:
      efficacy of a low-volume, intermediate-dose regimen.
AB  - OBJECTIVE: To report the clinical outcomes of highly active antiretroviral
      therapy (HAART)-naive, human immunodeficiency virus (HIV)-positive patients with
      newly diagnosed cytomegalovirus (CMV) retinitis receiving intravitreal injections
      of a low-volume intermediate maintenance dose (1.0 mg/0.02 ml) of ganciclovir.
      DESIGN: Nonrandomized, retrospective, interventional series. PARTICIPANTS: A
      consecutive cohort of 34 eyes from 24 HAART-naive patients with AIDS and
      diagnosed with CMV retinitis by retinal specialists at the Singapore Communicable
      Disease Centre. INTERVENTION: Patients received a maintenance dose of 1.0 mg/0.02
      ml of intravitreal ganciclovir once weekly after standard induction therapy with
      2.0 mg/0.04 ml of twice weekly intravitreal ganciclovir. MAIN OUTCOME MEASURES:
      Time to progression, visual acuity, and complications. Progression was observed
      using photographic documentation. RESULTS: The median time to progression was 152
      days (mean, 380.1 days, 95% confidence interval, 240.8-519.4). The median follow
      up was 95 days (mean, 207.9 days). Three eyes developed rhegmatogenous
      detachments, but there was no endophthalmitis after 1858 injections.
      Contralateral involvement of CMV retinitis occurred in 17.6% of the patients. The
      cost estimate for intravitreal injections over a 6-month period was 11.7% that of
      sustained-release implants for unilateral treatment and 11.1% that of daily
      continuous intravenous infusions and oral valganciclovir compared with bilateral
      treatments. CONCLUSIONS: Weekly low-volume, intermediate-dose (1.0 mg/0.02 ml)
      ganciclovir is an efficacious option in developing countries where newer options
      of sustained-release implants and oral valganciclovir are unavailable or
      prohibitively expensive. The regimen maintains a long time to progression,
      preserving vision while minimizing retinal toxicity complications.

PMID- 22137554
TI  - Measurement of soil contamination by radionuclides due to the Fukushima Dai-ichi
      Nuclear Power Plant accident and associated estimated cumulative external dose
      estimation.
AB  - Soil sampling was carried out at an early stage of the Fukushima Dai-ichi Nuclear
      Power Plant (FDNPP) accident. Samples were taken from areas around FDNPP, at four
      locations northwest of FDNPP, at four schools and in four cities, including
      Fukushima City. Radioactive contaminants in soil samples were identified and
      measured by using a Ge detector and included (129 m)Te, (129)Te, (131)I, (132)Te,
      (132)I, (134)Cs, (136)Cs, (137)Cs, (140)Ba and (140)La. The highest soil
      depositions were measured to the northwest of FDNPP. From this soil deposition
      data, variations in dose rates over time and the cumulative external doses at the
      locations for 3 months and 1y after deposition were estimated. At locations
      northwest of FDNPP, the external dose rate at 3 months after deposition was 4.8
      98 MUSv/h and the cumulative dose for 1 y was 51 to 1.0 * 10(3)mSv; the highest
      values were at Futaba Yamada. At the four schools, which were used as evacuation
      shelters, and in the four urban cities, the external dose rate at 3 months after
      deposition ranged from 0.03 to 3.8MUSv/h and the cumulative doses for 1 y ranged
      from 3 to 40 mSv. The cumulative dose at Fukushima Niihama Park was estimated as
      the highest in the four cities. The estimated external dose rates and cumulative
      doses show that careful countermeasures and remediation will be needed as a
      result of the accident, and detailed measurements of radionuclide deposition
      densities in soil will be important input data to conduct these activities.

PMID- 22137553
TI  - Posterior scleritis in children: clinical features and treatment.
AB  - OBJECTIVE: To summarize the clinical findings and treatment response in posterior
      scleritis affecting children and to compare these features with posterior
      scleritis affecting adults. DESIGN: Retrospective interventional case series.
      PARTICIPANTS: Twenty eyes of 13 patients aged younger than 18 years who were
      diagnosed with posterior scleritis in a tertiary referral center. INTERVENTION:
      Investigations and treatment were according to standard care, following published
      recommendations for scleritis. MAIN OUTCOME MEASURES: Clinical features,
      investigation results, treatment received, and visual outcome were studied.
      RESULTS: Twenty eyes of 13 patients (aged 5-16 years, median 11.53 years; 8
      female, 5 male) were included. Scleritis was unilateral in 6 cases and bilateral
      in 7 cases at presentation. The median presenting vision was 20/30. All eyes had
      T-sign demonstrable on B-scan ultrasound. Concurrent anterior segment signs
      included anterior uveitis (80.0%) and anterior scleritis (20.0%). Posterior
      segment signs included optic disc swelling (95.0%) and retinal striae (85.0%). No
      underlying connective tissue disorder was diagnosed in any patient. Scleritis
      resolved with oral nonsteroidal anti-inflammatory agent alone in 1 patient (8%).
      Twelve patients (92.3%) received oral corticosteroid. Immunosuppressive agents
      were required in 11 patients (84.6%) because of relapse or intolerance to
      corticosteroid. The median final vision at 1 year was 20/20. Seven patients
      (63.6%) remained on immunosuppression at latest follow-up (median 4 years).
      CONCLUSIONS: Common features of posterior scleritis include concurrent anterior
      uveitis, disc swelling, and retinal striae. B-scan ultrasound demonstrating T
      sign was the most useful confirmatory investigation in all cases. Systemic
      association is uncommon. Aggressive therapy with systemic corticosteroid achieves
      resolution mostly within the first year. Long-term immunosuppression is often
      required to prevent recurrence. Visual outcome is favorable. FINANCIAL
      DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any
      materials discussed in this article.

PMID- 22137555
TI  - 7Be aerosols and their deposition on the sea: a possible method to estimate trace
      metals deposition on the sea.
AB  - The activity size distributions of (7)Be aerosols in different size fractions
      (<0.39 MUm, 0.39-0.69 MUm, 0.69-1.3 MUm, 1.3-2.1 MUm, 2.1-4.2 MUm, 4.2-10.2 MUm
      and >10.2 MUm) were determined at the city of Thessaloniki, Greece, Eastern
      Mediterranean. The Activity Median Aerodynamic Diameter (AMAD) values ranged from
      0.58 to 1.22 MUm while more of the 80% of the (7)Be activity was associated with
      particles smaller than 1.3 MUm. Sea salt aerosol particles were defined in a
      small size range, lower than 0.39 MUm. Field measurements at a coastal location
      allow the estimation of (7)Be deposition on the sea. Since the (7)Be aerosol
      particles were mainly below 1 MUm, scavenging by precipitation was the main
      process depositing (7)Be on the sea. Acting as an excellent tracer, (7)Be could
      be used for determination of the deposition of the trace metals on the sea, since
      they are expected to be deposited at similar rate by wet and dry deposition
      processes as the (7)Be.

PMID- 22137556
TI  - Analysis of data from sensitive U.S. monitoring stations for the Fukushima Dai
      ichi nuclear reactor accident.
AB  - The March 11, 2011 9.0 magnitude undersea megathrust earthquake off the coast of
      Japan and subsequent tsunami waves triggered a major nuclear event at the
      Fukushima Dai-ichi nuclear power station. At the time of the event, units 1, 2,
      and 3 were operating and units 4, 5, and 6 were in a shutdown condition for
      maintenance. Loss of cooling capacity to the plants along with structural damage
      caused by the earthquake and tsunami resulted in a breach of the nuclear fuel
      integrity and release of radioactive fission products to the environment. Fission
      products started to arrive in the United States via atmospheric transport on
      March 15, 2011 and peaked by March 23, 2011. Atmospheric activity concentrations
      of (131)I reached levels of 3.0*10(-2) Bqm(-3) in Melbourne, FL. The noble gas
      (133)Xe reached atmospheric activity concentrations in Ashland, KS of 17 Bqm(-3).
      While these levels are not health concerns, they were well above the detection
      capability of the radionuclide monitoring systems within the International
      Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty.

PMID- 22137557
TI  - Laboratory studies on formation and minimisation of polychlorinated
      dibenzodioxins and -furans (PCDD/F) in secondary aluminium process.
AB  - The objectives of this work were to study the formation mechanisms of
      polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/F) in
      thermal aluminium recycling processes by use of laboratory experiments. The
      pattern of isomers of PCDD/F indicates that de novo synthesis is important in
      aluminium smeltery. The mechanisms of PCDD/F formation in aluminium smelting are
      similar to that of various incineration processes of waste material. The results
      of bioanalysis (EROD-test) confirms the existence of de novo synthesis of PCDD/F,
      but points out to the existence to some additional, toxic compounds of unknown
      structure. To reduce the amount of PCDD/F the input of carbon at the metal should
      be reduced; in addition the metal smeltery plants should be cleaned from fly ash
      particles. It is suggested to use good primary methods in the technical plants
      like constant feeding of the metal into the oven will minimise PCDD/F
      concentration. The biological EROD-bioassay is a good tool to estimate PCDD/F-TEQ
      values also for this technical process simulated in the laboratory.

PMID- 22137558
TI  - Detection limits can influence the interpretation of pesticide monitoring data in
      Canadian surface waters.
AB  - Water quality monitoring programs rely on residue data that are frequently left
      censored, due to some observations occurring below the Method Detection Limit
      (MDL). Our objective was to determine the influence the MDL has on the
      interpretation of pesticide residues in surface waters. Water samples from
      tributaries in southern and central Ontario were collected by Environment Canada
      from 2003 to 2008 and were analyzed for 27 pesticides, with MDLs that averaged
      7.02 ng(-1) L (range 0.39-25.1 ng(-1) L). We then simulated MDLs ranging from 25
      to 1700 ng(-1) L, to determine the impact this would have on the reporting of
      pesticide concentrations and detections. The mean number of pesticides detected
      simultaneously declined with increasing, i.e. less sensitive MDLs, from 5.02
      pesticides (native MDL) to 0.08 pesticides detected (MDL<1700 ng(-1) L). We
      compared the proportion of sites where pesticides were detected in surface waters
      under five MDL scenarios for 13 selected pesticides. The proportions decreased
      sharply with increasing MDLs. We calculated detection probabilities in an effort
      to compensate for higher MDLs using maximum likelihood; while adjusting for
      detection probabilities generally improved estimates of the presence of
      pesticides, as the MDLs increased the ability to compensate for detection
      probabilities deteriorated and became unviable at high MDLs. Depending on the
      method of substitution for observations below MDL (replacement with 1/2 * or 0 *
      MDL), the mean and median pesticide residues became increasingly over- and
      underestimated, respectively, at higher MDLs. Although monitoring programs that
      are focused on exceedences of water quality guidelines may not require low MDLs,
      the achievable goals of monitoring programs oriented towards other ecological and
      toxicological objectives may be limited by higher MDLs.

PMID- 22137559
TI  - Expression and clinical significance of ezrin in non--small-cell lung cancer.
AB  - BACKGROUND: Ezrin is known to regulate cellular survival, adhesion, migration,
      and invasion and has been identified as 1 of the key components of tumor
      progression and metastasis. The purpose of this study was to evaluate the
      clinicopathologic and prognostic significance of ezrin expression in non-small
      cell lung cancer (NSCLC). MATERIALS AND METHODS: We investigated the expression
      pattern of ezrin immunohistochemically in 89 paraffin samples of NSCLC between
      January 1998 and December 2006 and conducted survival analyses. In addition, 73
      frozen specimens (including tumorous and precancerous tissues) of NSCLC and 28
      frozen specimens of benign pneumonic diseases collected between January 2009 and
      December 2009 were analyzed by Western blot and reverse transcriptase-polymerase
      chain reaction (RT-PCR). RESULTS: In 89 paraffin samples, ezrin was expressed in
      40 cases, either in the cytoplasm or on the membrane. Ezrin-positive expression
      was significantly associated with increased tumor stage and lymph node (LN)
      metastasis. The positive rate of cytoplasm expression was significantly
      associated with LN metastasis. Importantly, ezrin-positive expression
      independently predicted inferior overall survival (OS) and disease-free survival
      (DFS). In 73 frozen specimens of NSCLC and 28 frozen specimens of benign
      pneumonic diseases, the ezrin mRNA, protein, and phospho-ezrin protein
      expressions in tumorous tissues were higher than they were in precancerous
      tissues and benign pneumonic tissues. CONCLUSION: These results suggested that
      high-level ezrin expression contributed to NSCLC progression and that
      phosphorylation and subcellular translocation of ezrin might be the important
      mechanisms. Ezrin might be a potential prognostic marker of progression in NSCLC.

PMID- 22137560
TI  - FATS expression is associated with cisplatin sensitivity in non small cell lung
      cancer.
AB  - BACKGROUND: Although the survival benefit of cisplatin-based adjuvant
      chemotherapy has been proven for patients with non small cell lung cancer
      (NSCLC), the resistance to cisplatin and its dose-dependent side effects remain a
      challenge. Improvement in survival and reduction of side effects require a
      biomarker capable of defining the response to cisplatin treatments in patients
      with NSCLC. FATS is a newly identified tumor suppressor involved in DNA damage
      induced carcinogenesis. In this study, we investigated whether the quantified
      mRNA expression of FATS can predict cisplatin sensitivity in NSCLC. METHODS: The
      expression level of FATS mRNA in tumor samples from patients receiving an initial
      diagnosis of NSCLC (n=89) was determined by quantitative real-time reverse
      transcription PCR. The histological characteristics of patients were
      retrospectively reviewed. Cisplatin-induced apoptosis in NSCLC cells was
      evaluated by flow cytometry after Annexin V staining. RESULTS: The mRNA level of
      FATS was significantly downregulated in NSCLC samples compared with normal
      tissues from the same patient (P=0.001). Low level of FATS mRNA expression was
      correlated with poor overall survival in NSCLC (P=0.030). For those NSCLC
      patients receiving cisplatin-based chemotherapy, the overall survival was
      significantly longer in FATS-high subgroup than that in FATS-low subgroup
      (P=0.038). Multivariate analysis revealed the independent value of FATS mRNA in
      predicting the overall survival for NSCLC patients receiving cisplatin-based
      chemotherapy. Furthermore, enhanced expression of FATS significantly sensitized
      NSCLC cells to cisplatin-induced apoptosis. CONCLUSION: The relatively high
      expression of FATS mRNA provides a new biomarker for a good outcome in patients
      receiving cisplatin-based chemotherapy.

PMID- 22137561
TI  - Specific functional asymmetries of the human visual cortex revealed by functional
      near-infrared spectroscopy.
AB  - Based on multiple invasive reports and neuroimaging studies, it is well
      established that the cytoarchitecture of the visual cortex is related to its
      functional organization, namely, its retinotopy. The present study aimed to
      further investigate retinotopic mapping as well as specific vertical and
      horizontal functional asymmetries within the human visual cortex using functional
      near-infrared spectroscopy (fNIRS). Black and white wedge checkerboard stimuli
      were randomly presented to the four visual field (VF) quadrants of eight healthy
      adults in order to quantify and compare the localization and the amplitude of
      hemodynamic cortical responses to each VF quadrant. Results showed the expected
      activation in the contralateral hemisphere, with respect to the side of the
      stimulated quadrant. We also measured significantly stronger activations in the
      upper visual cortex when low hemifield stimuli were presented compared to
      activations in the lower visual cortex when upper hemifield stimuli were shown,
      especially when the stimulation was presented in the right visual field. These
      findings confirm the vertical asymmetry of the visual cortex previously reported
      by neuroimaging and behavioral studies. More importantly, the present work
      confirms the reliability of the fNIRS technique for functional mapping of the
      human brain.

PMID- 22137562
TI  - Cells in the female retrotrapezoid region upregulate c-fos in response to 10%,
      but not 5%, carbon dioxide.
AB  - The retrotrapezoid nucleus (RTN) is thought to regulate breathing in response to
      changes in blood carbon dioxide (CO(2)), and to make a vital contribution to
      respiratory drive, especially during sleep. However, cells in the female RTN fail
      to upregulate c-fos in response to low level CO(2) exposure, while cells in the
      male RTN have a robust upregulation of c-fos in response to low level CO(2)
      exposure. In this study, we examined the possibility that the female RTN has a
      higher threshold for c-fos upregulation in response to CO(2). Following exposure
      of Fos-Tau-LacZ (FTL) transgenic mice to 10% CO(2), c-fos was upregulated in just
      as many cells in the female as in the male RTN. In addition, the male RTN
      responded equivalently to 5% and 10% CO(2), consistent with a lack of a dose
      response to CO(2) in the male RTN. Cells in the nearby facial nucleus upregulated
      c-fos in the same number of cells regardless of sex or gas exposure, confirming
      that the sex difference in the RTN is unique to that nucleus. We propose that the
      male and female RTN upregulate c-fos differently in response to CO(2) due to
      differences in the transcriptional regulation by estrogens of genes that encode
      proteins related to neuronal excitability or specifically related to central
      chemoreception, such as potassium channels. These findings could have clinical
      relevance to sleep related breathing disorders that disproportionately affect
      males, including the sudden infant death syndrome and sleep apnea.

PMID- 22137563
TI  - Forced swim stress elicits region-specific changes in CART expression in the
      stress axis and stress regulatory brain areas.
AB  - CART mRNA and peptides are highly expressed in the anatomical structures
      composing the hypothalamo-pituitary-adrenal (HPA) axis and sympatho-adrenal
      system. Anatomical and functional studies suggest that CART peptides may have a
      role in the regulation of the neuroendocrine and autonomic responses during
      stress. Our previous study showed that CART peptides increased significantly in
      the male hypothalamus and amygdala 10min after the forced swim stress. The
      present study aimed to examine the effect of forced swim stress on CART peptide
      expression in selected brain regions, including those where CART peptide
      expression has not been reported before (frontal cortex, pons, medulla
      oblongata), as well as in endocrine glands related to stress in male Sprague
      Dawley rats. A total of 16 (n=8) animals were used, including control groups.
      Rats were subjected to forced swim on two consecutive days, and sacrificed on the
      second day, 2h after the termination of the stress procedure. Frontal cortex,
      pons, medulla oblongata, hypothalamus, pituitary and adrenal glands were
      dissected and homogenized. CART peptide expression in these tissues was measured
      by Western Blotting and six different CART peptide fragments were identified. Our
      results showed that forced swim stress elicited region-specific changes in CART
      peptide expression. CART was upregulated in the frontal cortex, hypothalamus,
      medulla oblongata and adrenal gland while there was no change in the pons and
      pituitary. Enhanced CART peptide fragments in these brain regions and adrenal
      glands may have a role in the regulation of the HPA and sympatho-adrenal axis
      activity during stress response.

PMID- 22137564
TI  - Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR)
      association with antidepressant efficacy.
AB  - In the last decade the serotonin transporter gene promoter polymorphism (5
      HTTLPR) was likely the most studied genetic variant as predictor of
      antidepressant response. Nevertheless results are not consistent across studies
      and previous meta-analysis, since various factors seem to modulate its effect on
      antidepressant response. With the aim of clarifying this issue, we systematically
      reviewed literature, selecting 33 studies for an exploratory analysis without any
      a priori hypothesis. Then we analyzed separately 19 studies performed on
      Caucasians and 11 on Asians. We tested two phenotypes--remission and response
      rates--and three genotype comparisons--ll versus ls/ss, ss versus ll/ls and ll
      versus ss - using the Cochrane review manager. Evaluations were performed
      separately for SSRIs and mixed/other drugs. Possible clinical modulators were
      investigated. In the exploratory analysis, we found an association between l
      allele and l/l genotype and remission. When the analysis was split for ethnic
      group, in Caucasians we found an association between l allele and both response
      (OR = 1.58, C.I. 1.16-2.16, p = 0.004), and remission (OR = 1.53, C.I. 1.14-2.04,
      p = 0.004) in the SSRI group. Only a marginal association between l allele and
      remission (OR = 1.41, C.I. 1.02-1.95, p = 0.04) survived pooling together mixed
      antidepressant treatments. In Asians, a small effect of 5-HTTLPR on remission for
      mixed antidepressants was detected (OR = 2.10, C.I. 1.15-3.84, p = 0.02). Gender,
      age and age at onset modulated the association in Caucasians. Gender, age and
      depression severity at baseline modulated the association in Asians. In
      conclusion, in Caucasians 5-HTTLPR may be a predictor of antidepressant response
      and remission, while in Asians it does not appear to play a major role.

PMID- 22137565
TI  - A validation of cognitive biomarkers for the early identification of cognitive
      enhancing agents in schizotypy: a three-center double-blind placebo-controlled
      study.
AB  - A number of compounds aimed at improving cognition in schizophrenia have failed
      to demonstrate efficacy in Phase 2 clinical trials. Translational studies using
      biomarkers in surrogate populations, such as schizotypy, could be used to assess
      the efficacy of novel compounds. In this study, we aimed to validate the
      sensitivity and inter-site reliability of cognitive biomarkers (working memory (N
      back), spatial working memory (SWM) and verbal fluency (VF) tasks) to detect the
      schizotypy phenotype and its reversal by psychotropic drugs. Healthy volunteers
      scoring high or average on a schizotypal personality measure (122 in each group)
      were randomized to receive a single dose of risperidone, amisulpride, nicotine or
      placebo in a double-blind, between-subject design. We found evidence for a poorer
      performance on N-back and VF tasks in the high schizotypy group, replicating
      previous research. This effect was counteracted by amisulpride on N-back: it
      improved working memory in high schizotypy group but impaired the controls. A
      similar pattern was seen in SWM and VF. We interpret this finding in the light of
      the dopamine enhancing action of amisulpride when given in low doses. In
      contrast, risperidone impaired both groups and nicotine had a beneficial effect
      for the low baseline performers only. These effects were consistent across sites.
      These data demonstrates the utility of biomarkers in detecting the effect of
      schizotypy and its reversal by drugs that enhance dopamine and cholinergic
      function. Studies using similar design could help the early assessment of
      potential of compounds designed to improve cognition in schizophrenia.

PMID- 22137566
TI  - The magnetic map of hatchling loggerhead sea turtles.
AB  - Young loggerhead sea turtles (Caretta caretta) from eastern Florida, U.S.A.,
      undertake a transoceanic migration in which they gradually circle the North
      Atlantic Ocean before returning to the North American coast. Hatchlings in the
      open sea are guided at least partly by a 'magnetic map' in which regional
      magnetic fields function as navigational markers and elicit changes in swimming
      direction at crucial locations along the migratory route. The magnetic map exists
      in turtles that have never migrated and thus appears to be inherited. Turtles
      derive both longitudinal and latitudinal information from the Earth's field, most
      likely by exploiting unique combinations of field inclination and intensity that
      occur in different geographic areas. Similar mechanisms may function in the
      migrations of diverse animals.

PMID- 22137567
TI  - The role of auditory feedback in vocal learning and maintenance.
AB  - Auditory experience is critical for the acquisition and maintenance of learned
      vocalizations in both humans and songbirds. Despite the central role of auditory
      feedback in vocal learning and maintenance, where and how auditory feedback
      affects neural circuits important to vocal control remain poorly understood.
      Recent studies of singing birds have uncovered neural mechanisms by which
      feedback perturbations affect vocal plasticity and also have identified feedback
      sensitive neurons at or near sites of auditory and vocal motor interaction.
      Additionally, recent studies in marmosets have underscored that even in the
      absence of vocal learning, vocalization remains flexible in the face of changing
      acoustical environments, pointing to rapid interactions between auditory and
      vocal motor systems. Finally, recent studies show that a juvenile songbird's
      initial auditory experience of a song model has long-lasting effects on
      sensorimotor neurons important to vocalization, shedding light on how auditory
      memories and feedback interact to guide vocal learning.

PMID- 22137568
TI  - Assessing the potential underestimation of sediment and nutrient loads to the
      Great Barrier Reef lagoon during floods.
AB  - Much of the sediment and nutrient load to the Great Barrier Reef (GBR) lagoon
      happens during over bank floods, when discharge can be significantly
      underestimated by standard river gauges. This paper assesses the potential need
      for a flood load correction for 28 coastal rivers that discharge into the GBR
      lagoon. For each river, daily discharge was divided into flows above and below a
      'flood' threshold to calculate the mean annual percentage flow above this
      threshold. Most GBR rivers potentially need a flood load correction as over 15%
      of their mean annual flow occurs above the minor flood level; only seven rivers
      need little/no correction as their flood flows were less than 5% of the mean
      annual flow. Improved assessment of the true load of materials to the GBR lagoon
      would be an important contribution to the monitoring and reporting of progress
      towards Reef Plan and associated marine load targets.

PMID- 22137569
TI  - Suboptimal anti-epilepsy drug use is common among indigenous patients with
      seizures presenting to the emergency department.
AB  - We aimed to explore the causes of higher than expected rates of Indigenous
      emergency department (ED) seizure presentations. A questionnaire was administered
      to adult patients presenting with seizure to an ED in Far North Queensland. Over
      15 months, among 260 presentations with seizure (22% Indigenous), 50% non
      Indigenous patients, and 45% Indigenous patients completed the questionnaire.
      Risk factors for alcohol misuse were common in both groups (50% Indigenous, 43%
      non-Indigenous; p = 0.50), as were rates of reported head injury (50% Indigenous,
      44% non-Indigenous; p = 0.50). However, 47% Indigenous patients, compared to 19%
      non-Indigenous patients (p < 0.05) reported missing anti-epileptic tablets at
      least twice weekly, representing clinically relevant medication non-adherence.
      This was the first reported seizure presentation for 12% Indigenous patients and
      26% non-Indigenous patients. We conclude that among ED seizure presentations,
      alcohol excess and prior head injury are commonly observed, in both Indigenous
      and non-Indigenous patients. However, Indigenous patients have higher rates of
      anti-convulsant non-adherence, likely contributing to ED presentations.

PMID- 22137570
TI  - Polymorphisms of vascular cell adhesion molecule1 (VCAM1) in polycystic ovary
      syndrome determined by quantitative real-time polymerase chain reaction and
      melting curve analysis.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrinopathy associated
      with increased risk of obesity, insulin resistance (IR) and type 2 diabetes
      mellitus. Low-grade chronic inflammation and imbalance between pro- and anti
      inflammatory cytokines has been proposed to play a role in the pathogenesis.
      Vascular cell adhesion molecule1 (VCAM1) is among the parameters reflecting low
      grade chronic inflammation whose expression is increased by pro-inflammatory
      cytokines. This study examined the possible association of T-1591C and T-833C
      single nucleotide polymorphisms (SNPs) of VCAM1 gene with the occurrence and the
      clinical/biochemical characteristics of PCOS. STUDY DESIGN: We analyzed genotype
      and allele distributions of the above-mentioned SNPs in DNA from peripheral blood
      leukocytes of 169 patients with PCOS and 179 healthy women, by a real-time
      polymerase chain reaction (PCR) method combined with melting curve analysis using
      fluorescence-labeled hybridization probes. RESULTS: No significant associations
      between PCOS and the variant alleles of VCAM1-1591 (OR: 1.09, 95% CI=0.74-1.58)
      and -833 (OR: 1.42, 95% CI=0.59-3.43) were observed. None of the studied
      polymorphisms was found to affect IR indices and sVCAM levels significantly.
      However, PCOS women heterozygous for VCAM1-1591 polymorphism (CT) had significant
      increased triglyceride and decreased HDL-C in comparison with wild homozygous
      (TT) ones. CONCLUSIONS: Although there is no association between -1591 and -833
      polymorphisms of VCAM1 gene and susceptibility to PCOS, higher triglyceride and
      lower HDL-C in VCAM1-1591 CT genotype suspect that heterozygous patients are
      prone to increased risk for atherosclerosis and cardiovascular disease. In
      addition, bearing in mind that PCOS is a consequence of interaction between
      various genetic and environmental factors, the association between heterozygocity
      of VCAM1-1591 polymorphism and some lipid parameters may depend on the impact of
      other known or unknown polymorphisms, being in linkage disequilibrium with this
      locus of VCAM1 gene.

PMID- 22137571
TI  - Profiles of women presenting for abortions in Singapore: focus on teenage
      abortions and late abortions.
AB  - OBJECTIVE: Teenage abortions predispose women to adverse pregnancy outcomes in
      subsequent pregnancies such as anemia, stillbirths, preterm deliveries and low
      birth weight babies. We aim to profile the women presenting for abortions in our
      institution and determine risk factors for late presentation for abortions. STUDY
      DESIGN: In this retrospective cohort study, all women who underwent an abortion
      at the National University Hospital, Singapore, from 2005 to 2009 were recruited.
      Data was obtained from a prepared questionnaire during the mandatory pre-abortion
      counseling sessions. Profiles of women aged <20 years were compared with those >=
      20 years old using Chi-square test if the assumptions for Chi-square test were
      met; otherwise, Fisher's exact test was carried out. Logistic regression was used
      to investigate the risk factors for second trimester termination of pregnancy.
      RESULTS: 2109 women presented for induced abortions, of which 1998 had single
      abortion throughout the course of the study. The mean age of women with single
      abortion was 29.1 years (sd 7). In the group of women with single abortion, 182
      (9.1%) were teenage abortions. In contrast to women >= 20 years of age, pregnant
      teenagers were more likely not to have used any contraception (51.1% vs. 25.2%)
      and more likely to present late for abortions (39.6% vs. 15.9%). Other risk
      factors for late presentation for abortions include Malay ethnicity, singlehood,
      nulliparity and lack of prior usage of contraception. CONCLUSION: Teenagers are
      more likely to have no prior contraceptive usage and to present late for
      abortions. Lack of proper sexual education and awareness of contraceptive
      measures may have a major contributory factor to such a trend in teenage
      abortions. Recommendations have been made in order to curb this societal problem.

PMID- 22137572
TI  - Deep infiltrating endometriosis with obstructive uropathy secondary to ureteral
      endometriosis.

PMID- 22137573
TI  - Natural history of functional gastrointestinal disorders: comparison of two
      longitudinal population-based studies.
AB  - BACKGROUND: Functional gastrointestinal disorders are common but information on
      their natural history is limited. AIMS: To document the natural history of
      functional gastrointestinal disorders in a population based study and to compare
      with the Olmsted County study. METHOD: A questionnaire was mailed to the same age
      and gender-stratified random sample of the Icelandic population aged 18-75 in
      1996 and 2006. Results were compared to the Olmsted County study. RESULTS:
      Prevalence of functional gastrointestinal disorder symptoms was stable between
      these periods in time: 16.9% and 17.2% for irritable bowel syndrome, and 4.8% and
      6.1% for functional dyspepsia. Onset of each disorder was more often higher in
      the Olmsted County study than in Iceland. Disappearance rates were similar for
      both studies. Transition probabilities varied across the different subgroups and
      were different between studies. The same proportion had the same symptoms in the
      initial and final studies. More subjects had no symptoms in Iceland (52% vs. 40%)
      and different symptoms at follow up (38% vs. 23%). CONCLUSION: Prevalence of
      functional gastrointestinal disorder symptoms was stable over time but the
      turnover in symptoms was high. A higher number of subjects had no symptoms in
      Iceland than in Olmsted County and there was a greater variation in subjects
      having different symptoms at follow up.

PMID- 22137574
TI  - The changing conceptual basis of trabeculectomy: a review of past and current
      surgical techniques.
AB  - The original intent of glaucoma surgery was to allow aqueous humor to exit more
      easily either through the sclera or into the suprachoroidal space. The former
      came to be called, generically, a glaucoma filtering procedure. As this surgery
      evolved, some explored the concept of lowering pressure without producing a hole
      in the sclera, with its resultant "filtering bleb." For example, Cairns hoped
      that cutting open the edges of Schlemm's canal would allow aqueous to leave
      without producing a filtering bleb; however, it became apparent that Cairns's
      "trabeculectomy" only worked when a filtering bleb developed. The goal of today's
      trabeculectomy is the creation of a longlasting transscleral fistula. In fact,
      trabeculectomy is a misnomer as excision of trabecular meshwork is unimportant.
      Frequently, the tissue excised to create a trans-scleral fistula is sclera,
      cornea, or both. The current trabeculectomy is really a guarded
      sclerokeratectomy. Newer techniques hope to increase aqueous outflow through
      Schlemm's canal to avoid complications associated with subconjunctival filtering
      blebs. Non-penetrating glaucoma surgeries (deep sclerectomy, viscocanalostomy)
      and ab interno trabecular surgery attempt to lower intraocular pressure with bleb
      less procedures. We describe the recent evolution of glaucoma surgery,
      particularly the idea that intraocular pressure may be lowered satisfactorily
      without creating a filtering bleb.

PMID- 22137576
TI  - Bacterial post-traumatic endophthalmitis.

PMID- 22137578
TI  - Functional and sensitive outcomes after tongue reconstruction: about a series of
      30 patients.
AB  - Few studies reported both functional and sensitive long-term evaluations after
      tongue reconstruction. The aim of this study was to assess functional outcomes
      and sensitive recovery after tongue reconstruction with fasciocutaneous free flap
      (FCFF) or musculocutaneous pedicled flap (MCPF) without nerve anastomosis. We
      enrolled 30 patients having no recurrence from a consecutive series of 79 tongue
      reconstructions as part of a cancer treatment. All patients were submitted to
      functional and sensitive tests. The functional study included intelligibility,
      tongue motility, food, and swallowing scores. Flap sensibility was evaluated too.
      Male-to-female sex ratio was 6.5 with a mean age of 52 years old. The lesions
      were mainly advanced (T3-T4 73%). Mobile tongue and base of tongue resection was
      carried out in 43% of cases, and resection was limited to the oral tongue for
      53%. Twenty-one FCFF and nine MCPF were performed. The mean follow-up was 2 years
      and 11 months. Swallowing (slightly impaired 63%), food (normal 40%), and
      intelligibility (excellent 77%) assessments were satisfactory. Spontaneous
      sensory recovery was regularly observed (mean response 62%). The two groups FCFF
      and MCPF were similar regarding population and tumors characteristics. Functional
      results were higher in case of FCFF (food score p=0.05; intelligibility p=0.04).
      No difference was observed on sensitive recovery. This study emphasizes good
      functional results either for swallowing or intelligibility, with higher scores
      for the FCFF, strengthening the opinion that FCFF is the best choice for tongue
      reconstruction whenever possible.

PMID- 22137579
TI  - Cerebral hemispherectomy: sensory scores before and after intensive mobility
      training.
AB  - PURPOSE: It is unclear whether sensory modalities can be modified by
      rehabilitation and if sensory functions vary on the affected side many years
      after cerebral hemispherectomy. This pilot, proof-of-concept study assessed light
      touch and proprioception before and after 10 days of intensive mobility training
      in individuals after hemispherectomy. METHODS: Light touch and proprioception of
      the upper and lower extremity was measured using the Fugl-Meyer sensory subtest
      on the paretic side in 18 individuals with hemispherectomy before and after
      mobility training. Sensory scores and differences related to mobility training
      were compared with clinical variables. RESULTS: Patients were 7.1+/-5.7 years
      from time of surgery to sensory assessment and mobility training. Light touch
      scores were 81+/-22% and proprioception values were 64+/-23% of normal
      (p=0.0022). Light touch did not correlate with proprioception scores, and
      differences comparing after with before mobility training did not correlate. In
      multivariate analysis, younger age at seizure onset correlated with better light
      touch scores, and older age at onset correlated with improvements in light touch
      scores with mobility training. By comparison, proprioception scores were better
      in individuals with perinatal infarcts compared with Rasmussen encephalitis and
      Sturge-Weber. Post-training, proprioception scores were better in Sturge-Weber
      cases. CONCLUSION: Light touch was less affected than proprioception on the
      paretic side after cerebral hemispherectomy. Improvements with mobility training
      correlated with older age at seizure onset and etiology. These findings suggest
      that many years after epilepsy surgery sensory functions are not static
      supporting the notion of existing developmental neuroplasticity of the remaining
      cerebral cortex along with brain stem and spinal cord pathways.

PMID- 22137580
TI  - Ser7 phosphorylation of the CTD recruits the RPAP2 Ser5 phosphatase to snRNA
      genes.
AB  - The carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol
      II) comprises multiple heptapeptide repeats of the consensus Tyr1-Ser2-Pro3-Thr4
      Ser5-Pro6-Ser7. Reversible phosphorylation of Ser2, Ser5, and Ser7 during the
      transcription cycle mediates the sequential recruitment of transcription/RNA
      processing factors. Phosphorylation of Ser7 is required for recruitment of the
      gene type-specific Integrator complex to the Pol II-transcribed small nuclear
      (sn)RNA genes. Here, we show that RNA Pol II-associated protein 2 (RPAP2)
      specifically recognizes the phospho-Ser7 mark on the Pol II CTD and also
      interacts with Integrator subunits. siRNA-mediated knockdown of RPAP2 and
      mutation of Ser7 to alanine cause similar defects in snRNA gene expression. In
      addition, we show that RPAP2 is a CTD Ser5 phosphatase. Taken together, our
      results indicate that during transcription of snRNA genes, Ser7 phosphorylation
      facilitates recruitment of RPAP2, which in turn both recruits Integrator and
      dephosphorylates Ser5.

PMID- 22137582
TI  - Coinfection of Schistosoma (Trematoda) with bacteria, protozoa and helminths.
AB  - This review examines coinfection of selected species of Schistosoma with
      bacteria, protozoa and helminths and focuses on the effects of the coinfection on
      the hosts. The review is based mainly on tables that contain the salient
      information on the coinfecting organisms in vertebrate hosts. Further explanation
      and clarification of the tables are given in the text. A table is also provided
      that gives synoptic information on the 37 species in the 19 genera considered in
      this review. Coinfection studies with Schistosoma species and the other organisms
      were considered in six tables plus the accompanying text. Considerations of the
      Schistosoma interactions with another species of organism include studies on
      coinfection with Plasmodium, with protozoa other than Plasmodium; with
      Salmonella, with bacteria other than Salmonella; and with Fasciola, with
      helminths other than Fasciola. Numerous factors were found to influence the
      effects of coinfection on the vertebrate host, including organisms and hosts used
      in the studies, order and time interval between the first and the second
      infection, studies on natural versus experimental hosts, dosage of the infectious
      agents, strains and pedigrees of the parasites, age of hosts at time of exposure
      to the infectious agents and age of hosts at the time of necropsy. Overall, a
      prior infection with Schistosoma, particularly a patent infection, often has an
      effect on the subsequent infection by a protozoan, bacterium or other helminth.
      In relatively few cases, a prior infection with Schistosoma decreased the
      severity of the subsequent infection as with Helicobacter pylori, Fasciola
      hepatica, Echinostoma or Plasmodium, the latter only exhibiting this behaviour
      when coinfected with Schistosoma haematobium. More often, however, a prior
      infection with Schistosoma increased the severity of the second infection as with
      Leishmania, Toxoplasma gondii, Entamoeba histolytica, Staphylococcus aureus or
      Salmonella. In some of these coinfection studies, the increased severity of the
      subsequent infection was associated with a specific, prolonged form of the
      disease in humans, which has implications for patient treatment and recovery.
      Additional research is needed, particularly on Schistosoma coinfections which
      currently have a small body of research and are current problems in human
      populations. Examples of such Schistosoma interactions include the genera of
      Mycobacteria, Leishmania, Staphylococcus, Necator and Strongyloides. Hopefully,
      future studies will elucidate valuable new information on the interesting subject
      of coinfection of Schistosoma with other organisms.

PMID- 22137581
TI  - Chemical genetic screen for AMPKalpha2 substrates uncovers a network of proteins
      involved in mitosis.
AB  - The energy-sensing AMP-activated protein kinase (AMPK) is activated by low
      nutrient levels. Functions of AMPK, other than its role in cellular metabolism,
      are just beginning to emerge. Here we use a chemical genetics screen to identify
      direct substrates of AMPK in human cells. We find that AMPK phosphorylates 28
      previously unidentified substrates, several of which are involved in mitosis and
      cytokinesis. We identify the residues phosphorylated by AMPK in vivo in several
      substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and
      p21-activated protein kinase (PAK2). AMPK-induced phosphorylation is necessary
      for PPP1R12C interaction with 14-3-3 and phosphorylation of myosin regulatory
      light chain. Both AMPK activity and PPP1R12C phosphorylation are increased in
      mitotic cells and are important for mitosis completion. These findings suggest
      that AMPK coordinates nutrient status with mitosis completion, which may be
      critical for the organism's response to low nutrients during development, or in
      adult stem and cancer cells.

PMID- 22137583
TI  - Trichomonas vaginalis pathobiology new insights from the genome sequence.
AB  - The draft genome of the common sexually transmitted pathogen Trichomonas
      vaginalis encodes one of the largest known proteome with 60,000 candidate
      proteins. This provides parasitologists and molecular cell biologists alike with
      exciting, yet challenging, opportunities to unravel the molecular features of the
      parasite's cellular systems and potentially the molecular basis of its
      pathobiology. Here, recent investigations addressing selected aspects of the
      parasite's molecular cell biology are discussed, including surface and secreted
      virulent factors, membrane trafficking, cell signalling, the degradome, and the
      potential role of RNA interference in the regulation of gene expression.

PMID- 22137584
TI  - Cryptic parasite revealed improved prospects for treatment and control of human
      cryptosporidiosis through advanced technologies.
AB  - Cryptosporidium is an important genus of parasitic protozoa of humans and other
      vertebrates and is a major cause of intestinal disease globally. Unlike many
      common causes of infectious enteritis, there are no widely available, effective
      vaccine or drug-based intervention strategies for Cryptosporidium, and control is
      focused mainly on prevention. This approach is particularly deficient for
      infections of severely immunocompromised and/or suppressed, the elderly or
      malnourished people. However, cryptosporidiosis also presents a significant
      burden on immunocompetent individuals, and can, for example have lasting effects
      on the physical and mental development of children infected at an early age. In
      the last few decades, our understanding of Cryptosporidium has expanded
      significantly in numerous areas, including the parasite life-cycle, the processes
      of excystation, cellular invasion and reproduction, and the interplay between
      parasite and host. Nonetheless, despite extensive research, many aspects of the
      biology of Cryptosporidium remain unknown, and treatment and control are
      challenging. Here, we review the current state of knowledge of Cryptosporidium,
      with a focus on major advances arising from the recently completed genome
      sequences of the two species of greatest relevance in humans, namely
      Cryptosporidium hominis and Cryptosporidium parvum. In addition, we discuss the
      potential of next-generation sequencing technologies, new advances in in silico
      analyses and progress in in vitro culturing systems to bridge these gaps and to
      lead toward effective treatment and control of cryptosporidiosis.

PMID- 22137585
TI  - Assessment and monitoring of onchocerciasis in Latin America.
AB  - Onchocerciasis has historically been one of the leading causes of infectious
      blindness worldwide. It is endemic to tropical regions both in Africa and Latin
      America and in the Yemen. In Latin America, it is found in 13 foci located in 6
      different countries. The epidemiologically most important focus of onchocerciasis
      in the Americas is located in a region spanning the border between Guatemala and
      Mexico. However, the Amazonian focus straddling the border of Venezuela and
      Brazil is larger in overall area because the Yanomami populations are scattered
      over a very large geographical region. Onchocerciasis is caused by infection with
      the filarial parasite Onchocerca volvulus. The infection is spread through the
      bites of an insect vector, black flies of the genus Simulium. In Africa, the
      major vectors are members of the S. damnosum complex, while numerous species
      serve as vectors of the parasite in Latin America. Latin America has had a long
      history of attempts to control onchocerciasis, stretching back almost 100 years.
      The earliest programmes used a strategy of surgical removal of the adult
      parasites from affected individuals. However, because many of the adult parasites
      lodge in undetectable and inaccessible areas of the body, the overall effect of
      this strategy on the prevalence of infection was relatively minor. In 1988, a new
      drug, ivermectin, was introduced that effectively killed the larval stage
      (microfilaria) of the parasite in infected humans. As the microfilaria is both
      the stage that is transmitted by the vector fly and the cause of most of the
      pathologies associated with the infection, ivermectin opened up a new strategy
      for the control of onchocerciasis. Concurrent with the use of ivermectin for the
      treatment of onchocerciasis, a number of sensitive new diagnostic tools were
      developed (both serological and nucleic acid based) that provided the efficiency,
      sensitivity and specificity necessary to monitor the decline and eventual
      elimination of onchocerciasis as a result of successful control. As a result of
      these advances, a strategy for the elimination of onchocerciasis was developed,
      based upon mass distribution of ivermectin to afflicted communities for periods
      lasting long enough to ensure that the parasite population was placed on the road
      to local elimination. This strategy has been applied for the past decade to the
      foci in Latin America by a programme overseen by the Onchocerciasis Elimination
      Program for the Americas (OEPA). The efforts spearheaded by OEPA have been very
      successful, eliminating ocular disease caused by O. volvulus, and eliminating and
      interrupting transmission of the parasite in 8 of the 13 foci in the region. As
      onchocerciasis approaches elimination in Latin America, several questions still
      need to be addressed. These include defining an acceptable upper limit for
      transmission in areas in which transmission is thought to have been suppressed
      (e.g. what is the maximum value for the upper bound of the 95% confidence
      interval for transmission rates in areas where transmission is no longer
      detectable), how to develop strategies for conducting surveillance for
      recrudescence of infection in areas in which transmission is thought to be
      interrupted and how to address the problem in areas where the mass distribution
      of ivermectin seems to be unable to completely eliminate the infection.

PMID- 22137586
TI  - Chronology of the Middle to Upper Palaeolithic transition at Abric Romani,
      Catalunya.
AB  - This paper presents new data from Abric Romani, a key site in the region of
      Catalunya, northeastern Iberia, which is central to discussions of the transition
      between the Middle and Upper Palaeolithic in Europe. Until now, the Mid-Upper
      Paleolithic transition had been dated at the site through samples from the
      remaining baulk sections of levels A and B (typologically classified as 'earliest
      Aurignacian' and Mousterian, respectively) at the rear of the rockshelter, which
      were left from excavations in the late 1900s and early 1910s. We dated samples of
      bone and charcoal from these remnant sections with accelerator mass spectrometry
      (AMS) methods. We also analysed several humanly-modified artefacts (bone points
      and perforated shells) excavated from other areas of the same layers. From the
      initial series, we obtained ages of c. 20 ka BP (thousands of years before
      present); much younger than expected if they indeed dated to the early Upper
      Palaeolithic. We sampled additional material to test the robustness of these
      initial ages, and older determinations that were more comparable with the
      chronology outlined by Bischoff et al. (1988, 1994) resulted. All of the old and
      new results have been compared in a Bayesian model using the new INTCAL09 (14)C
      calibration dataset. The results appear to confirm the suggestion of some
      researchers (e.g., Zilhao and d'Errico, 1999) that there was no Aurignacian in
      the north of Iberia until c. 36,500 BP. The chronometric model shows a good level
      of agreement between the radiocarbon and U-series chronologies previously
      obtained, and the new results published in this paper.

PMID- 22137587
TI  - Comparison of the endocranial ontogenies between chimpanzees and bonobos via
      temporal regression and spatiotemporal registration.
AB  - This paper aims at quantifying ontogenetic differences between bonobo (Pan
      paniscus) and chimpanzee (Pan troglodytes) endocrania, using dental development
      as a timeline. We utilize a methodology based on smooth and invertible
      deformations combined with a metric of "currents" that defines a distance between
      endocranial surfaces and does not rely on correspondence between landmarks. This
      allows us to perform a temporal surface regression that estimates typical
      endocranial ontogenetic trajectories separately for bonobos and chimpanzees. We
      highlight non-linear patterns of endocranial ontogenetic change and significant
      differences between species at local anatomical levels rather than considering
      the endocranium as a uniform entity. A spatiotemporal registration permits the
      quantification of inter-species differences decomposed into a morphological
      deformation (accounting for size and shape differences independently of age) and
      a time warp (accounting for changes in the dynamics of development). Our
      statistical simulations suggest that patterns of endocranial volume (EV) increase
      may differ significantly between bonobos and chimpanzees, with an earlier phase
      of a relatively rapid increase (preferentially at some endocranial subdivisions)
      in the former and a much later phase of relatively rapid increase in the latter.
      As a consequence, the chimpanzee endocranium appears to reach its adult size
      later. Moreover, the time warp indicates that juvenile bonobos develop much
      slower than juvenile chimpanzees, suggesting that inter-specific ontogenetic
      shifts do not only concern EV increase, but also the rate of shape changes over
      time. Our method provides, for the first time, a quantitative estimation of inter
      specific ontogenetic shifts that appear to differentiate non-linearly.

PMID- 22137589
TI  - What's missing for evidence-based fever management? Is fever beneficial or
      harmful to humans?

PMID- 22137590
TI  - The role of felt or enacted criticism in understanding parent's help seeking in
      acute childhood illness at home: a grounded theory study.
AB  - BACKGROUND: Parents with young children often worry about whether or not to seek
      medical help for a sick child. Previous research identified parents' anxieties
      surrounding help seeking from health services but did not explore or explain the
      underlying psychosocial processes taking place in families at these times.
      OBJECTIVES: This paper presents findings from a British grounded theory study on
      family management of acute childhood illness at home, which provide an
      explanation for parent's helping seeking behaviours. DESIGN: Glaserian grounded
      theory methodology was used for the study. SETTING: The sampling sites for the
      study were in two towns in the East Midlands with population profiles close to
      the national average for the UK. PARTICIPANTS: Initial purposeful and later
      theoretical sampling resulted in a sample of fifteen families with children aged
      between 1 month and 8 years of age. METHODS: Four sets of data collection took
      place between 2001 and 2007. Unstructured family interviews were conducted with
      adult family members and a draw, write or tell technique was used to interview
      any children over 4 years of age. Theoretical sensitivity and constant
      comparative analysis were employed to achieve theoretical saturation around a
      core category. FINDINGS: Felt or enacted criticism teaches parents informal
      social rules which direct how they are expected to behave. Their desire to avoid
      such criticism of their moral status as 'good' parents creates significant hidden
      anxiety about when to seek medical help. This anxiety sometimes leads to late
      consultation with potentially serious consequences for their child's health.
      CONCLUSION: The grounded theory indicates the need for significant investment in
      the training of nurses and other health professionals to reduce parents' (and
      other patients') experiences of felt or enacted criticism and the consequent
      hidden anxiety. When parents are worried about their child's health, they need to
      be able to seek help from health professionals without fear of criticism. These
      conclusions are primarily limited to universal health care environments.

PMID- 22137591
TI  - Binding of cysteine thiolate to the Fe(III) heme complex is critical for the
      function of heme sensor proteins.
AB  - Heme sensor proteins function in response to the availability of the heme iron
      complex. The heme iron complex per se becomes the first signal for various
      important physiological functions of these proteins. The role of the heme iron
      complex in heme sensors is distinct from those of prototype heme proteins, such
      as hemoglobin, cytochromes c and P450, in which the heme iron complex is the
      functional center. For heme sensor proteins, association/dissociation of the heme
      iron complex regulates physiological processes, including catalysis,
      transcription, and other functions essential for cell survival. Importantly, the
      main binding/sensing site of the heme iron complex in heme sensor proteins is
      cysteine thiolate, which is critical for the heme sensing function. The role of
      the cysteine thiolate in heme sensor proteins differs from that of the P450
      system, in which the cysteine thiolate donates an electron to activate molecular
      oxygen bound to the heme iron complex trans to cysteine thiolate to facilitate
      the monooxygenase reaction. In this review, we discuss heme proteins with
      cysteine thiolate as the heme axial ligand, and summarize recent studies on heme
      sensor proteins and their molecular mechanisms. In particular, we focus on the
      controversial role of the heme iron complex in transcriptional regulation
      associated with circadian rhythms.

PMID- 22137592
TI  - Efficient double glycoconjugation to naturalize high molecular weight disperse
      dyes.
AB  - Commercially available Disperse Orange 29 (1a) and Disperse Red 1 (2a) were
      elaborated to glycoconjugated species, following a new version of a previously
      described 'naturalisation' procedure. Glutamic acid was chosen to achieve a
      double glycoconjugation, which is essential to give to the original disperse dye
      a water solubility suitable for reaching optimal dyeing conditions. UV-vis plot
      of the 'naturalised' species showed negligible differences when compared to those
      of the commercial dyes.

PMID- 22137593
TI  - Reorganization of synaptic inputs to the hypothalamic paraventricular nucleus
      during chronic psychogenic stress in rats.
AB  - BACKGROUND: Chronic stress in humans precipitates hyper-reactivity of the
      hypothalamic-pituitary-adrenocortical (HPA) axis and triggers symptoms associated
      with certain forms of depression. Reorganization of neuronal networks has been
      implicated in development of depression, however it remained unknown how chronic
      exposure to psychogenic challenges affects excitatory and inhibitory inputs to
      corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular
      nucleus that govern neuroendocrine stress response. METHODS: Rats (n = 32) were
      exposed for 21 days to chronic variable stress and their behavioral (sucrose
      preference) and hormonal (corticosterone) responses were followed together with
      electron microscopic stereologic analysis of excitatory and gamma-aminobutyric
      acid (GABA)-containing, inhibitory synapses on the CRH synthesizing neurons.
      RESULTS: Chronic stress in rats resulted in weight loss, anhedonia, and
      hyperactivity of hypothalamic-pituitary-adrenocortical axis. Following 3 weeks'
      exposure to variable psychologic stressors the number of synapses has been
      doubled in the paraventricular nucleus. Asymmetrical excitatory as well as
      GABAergic inhibitory synaptic contacts were increased on CRH neurons; however,
      the excitatory/inhibitory input ratio remained constant. In response to chronic
      stress, we found rearrangement of inhibitory GABA-containing inputs with the
      increase of contacts on dendrites and decrease at the soma region of CRH neurons.
      CONCLUSIONS: Significant remodeling of synaptic contacts was found on CRH neurons
      in response to chronic stress. This morphologic plasticity might be related to
      the hyperactivity of the HPA axis and to development of stress-related
      psychopathologies such as depression.

PMID- 22137595
TI  - Potential biomarkers for hepatoblastoma: results from the SIOPEL-3 study.
AB  - Hepatoblastoma (HB) is a rare malignant liver tumour found in infants. Many
      heterogeneous histological tumour subtypes exist. Although survival rates have
      improved dramatically in recent years with the use of platinum-based
      chemotherapy, there still exists a subset of HB that does not respond to
      treatment. There are currently no tumour biomarkers in use and in this study we
      aim to evaluate potential biomarkers to aid identification of relapse cases that
      would otherwise be overlooked by current prognostication. This may identify
      patients that would benefit from more aggressive therapy and could improve
      overall survival rates. We used immunohistochemistry to analyse the expression of
      beta-catenin, E-cadherin, Cyclin D1, Ki-67 and alpha-fetoprotein (AFP) protein in
      tumours from 91 patients prospectively enroled into the SIOPEL 3 clinical trial.
      The relationship between these biomarkers and clinicopathologic features and
      patient survival were statistically analysed. We identified one biomarker, Cyclin
      D1, which has a correlation with mixed epithelial/mesenchymal HB approaching
      significance (P = 0.07). Survival analysis using these markers has revealed two
      potential prognostic indicators; Cyclin D1 and Ki-67 (P = 0.01, 0.01).

PMID- 22137596
TI  - Salmonella persistence and transmission strategies.
AB  - Host-adapted strains of Salmonella enterica cause systemic infections and have
      the ability to persist systemically for long periods of time and pose significant
      public-health problems. Multidrug-resistant Salmonella enteric serovar Typhi (S.
      Typhi) and non-Typhoidal Salmonella (NTS) are on the increase, and are often
      associated with HIV infection. Chronically infected hosts are often asymptomatic
      and transmit disease to naive hosts via fecal shedding of bacteria, thereby
      serving as a critical reservoir for disease. Salmonella utilizes multiple
      strategies to evade and modulate host innate and adaptive immune responses in
      order to persist in the presence of a robust immune response. In addition, the
      intestinal microbiota plays a critical role in controlling Salmonella infection,
      disease, and transmissibility.

PMID- 22137594
TI  - The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and
      relapse to cocaine.
AB  - BACKGROUND: Relapse to cocaine seeking has been linked with low glutamate in the
      nucleus accumbens core (NAcore) causing potentiation of synaptic glutamate
      transmission from prefrontal cortex (PFC) afferents. Systemic N-acetylcysteine
      (NAC) has been shown to restore glutamate homeostasis, reduce relapse to cocaine
      seeking, and depotentiate PFC-NAcore synapses. Here, we examine the effects of
      NAC applied directly to the NAcore on relapse and neurotransmission in PFC-NAcore
      synapses, as well as the involvement of the metabotropic glutamate receptors 2/3
      (mGluR2/3) and 5 (mGluR5). METHODS: Rats were trained to self-administer cocaine
      for 2 weeks and following extinction received either intra-accumbens NAC or
      systemic NAC 30 or 120 minutes, respectively, before inducing reinstatement with
      a conditioned cue or a combined cue and cocaine injection. We also recorded
      postsynaptic currents using in vitro whole cell recordings in acute slices and
      measured cystine and glutamate uptake in primary glial cultures. RESULTS: NAC
      microinjection into the NAcore inhibited the reinstatement of cocaine seeking. In
      slices, a low concentration of NAC reduced the amplitude of evoked glutamatergic
      synaptic currents in the NAcore in an mGluR2/3-dependent manner, while high doses
      of NAC increased amplitude in an mGluR5-dependent manner. Both effects depended
      on NAC uptake through cysteine transporters and activity of the
      cysteine/glutamate exchanger. Finally, we showed that by blocking mGluR5 the
      inhibition of cocaine seeking by NAC was potentiated. CONCLUSIONS: The effect of
      NAC on relapse to cocaine seeking depends on the balance between stimulating
      mGluR2/3 and mGluR5 in the NAcore, and the efficacy of NAC can be improved by
      simultaneously inhibiting mGluR5.

PMID- 22137597
TI  - CCL2-2518 (A/G) polymorphisms and tuberculosis susceptibility: a meta-analysis.
AB  - BACKGROUND: It has been found that the -2518 C-C motif ligand (CCL)-2 promoter
      variant increases the risk of developing active tuberculosis (TB). OBJECTIVE: To
      study the association between -2518 variants and susceptibility to TB. DESIGN: We
      searched Medline, PubMed and the Wan Fang databases for human genetic studies on
      whether the -2518 CCL2 polymorphism influences the expression of active TB.
      Articles published from January 1998 to November 2010 were included. A random
      effects model was conducted in the meta-analysis. RESULTS: The CCL2-2518G allele
      (OR 1.51, 95%CI 1.11-2.04, P = 0.008) showed significant association with
      susceptibility to TB. In genotype analysis, the recessive model (CCL2 genotype
      GG, OR 1.66, 95%CI 1.19-2.33, P = 0.003) was slightly superior to the dominant
      model (G carrier genotypes OR 1.53, 95%CI 1.07-2.17, P = 0.018). These
      observations were prominent among Asians and Latin-Americans of Hispanic
      ancestry, but not in Africans from Ghana and South Africa. The presence of
      epistatic genes in one population but not in the other, environmental differences
      and pathogen virulence may account for this. CONCLUSION: The CCL2-2518G allele
      increases the risk of developing TB in Asians and Hispanics.

PMID- 22137598
TI  - Stereochemical diversity of AI-2 analogs modulates quorum sensing in Vibrio
      harveyi and Escherichia coli.
AB  - Bacteria coordinate population-dependent behaviors such as virulence by intra-
      and inter-species communication (quorum sensing). Autoinducer-2 (AI-2) regulates
      inter-species quorum sensing. AI-2 derives from the spontaneous cyclisation of
      linear (S)-4,5-dihydroxypentanedione (DPD) into two isomeric forms in dynamic
      equilibrium. Different species of bacteria have different classes of AI-2
      receptors (LsrB and LuxP) which bind to different cyclic forms. In the present
      work, DPD analogs with a new stereocenter at C-5 (4,5-dihydroxyhexanediones
      (DHDs)) have been synthesized and their biological activity tested in two
      bacteria. (4S,5R)-DHD is a synergistic agonist in Escherichia coli (which
      contains the LsrB receptor), while it is an agonist in Vibrio harveyi (LuxP),
      displaying the strongest agonistic activity reported so far (EC(50)=0.65MUM) in
      this organism. Thus, modification at C-5 opens the way to novel methods to
      manipulate quorum sensing as a method for controlling bacteria.

PMID- 22137600
TI  - MDS: Refining existing therapy through improved biologic insights.
AB  - Advances in therapy can essentially be measured using two parameters;
      introduction of a new agent which benefits an increased number of patients over
      prevailing treatments or more selective use of an existing drug by matching it to
      the biologic characteristics associated with response. In reviewing the
      therapeutic landscape of myelodysplastic syndromes (MDS), both should be applied
      to gauge the advances in therapy. While several new drugs are currently in
      clinical trials for the treatment of MDS, three drugs were approved for use in
      the last decade and sufficient time has elapsed to take stock of the benefit they
      have produced in the outcome of patients both in terms of survival and quality of
      life. For the two hypomethylating agents, response remains limited to 50%
      patients at best, and no strategy has evolved to allow for pre-selection of
      likely responders, however, 5-azacytidine has been associated with improvement in
      the survival of higher risk patients. The benefit of lenalidomide was found to be
      greater for del(5q) patients with transfusion dependent anemia and lower risk
      disease right from the start, although a quarter of the non-del(5q) patients also
      experienced complete transfusion independence with this agent. It is in this
      latter group of non-del(5q) cases that a strategy for potentially preselecting
      likely responders is suggested by the finding of an expression profile associated
      with response. In this paper, we will focus on defining our current understanding
      of the mechanisms of action of the existing FDA approved drugs in order to
      identify therapeutic strategies that are suitable for specific MDS subtypes. We
      expect that through advancing biologic insights, the use of such therapies will
      become more selective and refined.

PMID- 22137599
TI  - Discovery of inhibitors and substrates of brassinin hydrolase: Probing
      selectivity with dithiocarbamate bioisosteres.
AB  - Brassinin hydrolase (BHAb), an inducible enzyme produced by the plant pathogen
      Alternaria brassicicola under stress conditions, catalyzes the hydrolysis of the
      methyl dithiocarbamate group of the phytoalexin brassinin, to indolyl-3
      methanamine, methane thiol and carbonyl sulfide. Thirty four substrate inspired
      compounds, bioisosteres of brassinin and a range of related compounds, were
      evaluated as potential substrates and inhibitors of BHAb for the first time.
      While six compounds containing thiocarbamate, carbamate and carbonate groups
      displayed inhibitory activity against BHAb, only two were found to be substrates
      (thionecarbamate and dithiocarbamate). Methyl naphthalen-1-yl-methyl carbamate,
      the most potent inhibitor of the six, and methyl N'-(1-methyl-3
      indolylmethyl)carbamate inhibited BHAb through a reversible noncompetitive
      mechanism (K(i)=89+/-9 and 695+/-60MUM, respectively). Importantly, these
      carbamate inhibitors were resistant to degradation by A. brassicicola. Carbonates
      were also inhibitory of BHAb, but a quick degradation by A. brassicicola makes
      their potential use as crop protectants less likely. Overall, these results
      indicate that indolyl and naphthalenyl carbamates are excellent lead structures
      to design new paldoxins that could inhibit the detoxification of brassinin by A.
      brassicicola.

PMID- 22137601
TI  - Diffusion-weighted magnetic resonance imaging detects local recurrence after
      radical prostatectomy: initial experience.
AB  - Current conventional cross-sectional imaging techniques, such as contrast
      enhanced computed tomography and magnetic resonance imaging (MRI), are largely
      inaccurate in detecting local recurrence after radical prostatectomy. We report
      on five patients with biochemical recurrence after radical retropubic
      prostatectomy and pelvic lymph node dissection for whom local recurrence could
      only be detected with diffusion-weighted (DW) MRI. Prior to DW-MRI, all patients
      had negative digital rectal examinations, negative or equivocal conventional
      cross-sectional imaging, and negative bone scans. All suspicious lesions on DW
      MRI imaging were histologically proved to be local recurrences of prostate cancer
      after either transrectal ultrasound-guided or transurethral biopsy. These results
      should encourage other centres to test our findings.

PMID- 22137602
TI  - The future of urology.
AB  - The Future of Urology has been written in times of economic downturn, with the
      inevitable effects on health sector spending. Nevertheless, this document aims to
      define a path whereby the EAU can play a pivotal role in ensuring the highest
      standard of care throughout Europe, and by setting standards, throughout the rest
      of the world. The future of urology will be dependent on improved education and
      training leading to high quality urological care, and to developing a service
      that is patient focused. The patient focus is becoming increasingly important in
      urology. This means providing full information about disease processes and
      urological procedures to patients and allowing them to judge the quality of the
      urological service that they may choose. Education must start in medical school
      and as 5% of community medical practice is urology then every medical student
      must receive urological training. This also applies to nurses and the other
      professions allied to medicine (PAMS). The EAU should provide a urological
      curriculum for training of medical students, nurses and PAMS, as well as the more
      conventional curriculum for postgraduate training and continued medical education
      for urological specialists. An integrated EAU Knowledge and Learning Centre would
      provide an invaluable resource to patients and to those who deliver urologic care
      alike. With high quality training must come a vigorous assessment of knowledge
      and competence. In the future, the competence of all those delivering urological
      care will need to be assessed. For urologists in training and specialist
      urologists this will include not only an assessment of knowledge but an
      assessment of surgical competence. Improving quality will be supported by the
      continued subspecialisation of urology, ensuring that all urologists have a
      surgical portfolio which ensures their competency in the procedures they deliver.
      This will inevitably result in a concentration of urological services and indeed
      to the development of larger urological centres. The concept of Centres of
      Excellence could be developed to include all aspects and subspecialties of
      urological care. The SPO envisages that all urology will be carried out in
      Centres of Excellence which will vary in terms of their size and the range of
      urology offered, but nevertheless all urological care will be of the highest
      quality. Finally, the future of urology will depend on the medico-political
      interface and the EAU has a great deal to offer in this respect. The patterns of
      urological care differ throughout Europe but this should be seen as a challenge
      for the EAU to define quality, irrespective of the different methods of
      healthcare provision. The EAU has made extraordinary advances in the last two
      decades and the SPO hope this document will support the EAU's efforts to maintain
      its aim of improving urological care for the benefit of patients.

PMID- 22137603
TI  - Can video cameras replace visual estrus detection in dairy cows?
AB  - A 6-mo experiment was conducted in a dairy herd to evaluate a video system for
      estrus detection. From October 2007 to April 2008, 35 dairy cows of three breeds
      that ranged in age from 2 to 6 yr were included in the study. Four daylight
      cameras were set up in two free stalls with straw litter and connected to a
      computer equipped with specific software to detect movement. This system allowed
      the continuous observation of the cows as well as video storage. An observation
      method related to the functionality of the video management software ("Camera
      Icons" method) was used to detect the standing mount position and was compared to
      direct visual observation (direct visual method). Both methods were based on the
      visualization of standing mount position. A group of profile photos consisting of
      the full face, left side, right side, and back of each cow was used to identify
      animals on the videos. Milk progesterone profiles allowed the determination of
      ovulatory periods (reference method), and a total of 84 ovulatory periods were
      used. Data obtained by direct visual estrus detection were used as a control.
      Excluding the first postpartum ovulatory periods, the "Camera-Icons" method
      allowed the detection of 80% of the ovulatory periods versus 68.6% with the
      direct visual method (control) (P = 0.07). Consequently, the "Camera-Icons"
      method gave at least similar results to the direct visual method. When combining
      the two methods, the detection rate was 88.6%, which was significantly higher
      than the detection rate allowed by the direct visual method (P < 0.0005). Eight
      to 32 min (mean 20 min) were used daily to analyze stored images. When compared
      with the 40 min (four periods of 10 min) dedicated to the direct visual method,
      we conclude that the video survey system not only saved time but also can replace
      direct visual estrus detection.

PMID- 22137604
TI  - Postoperative spinal alignment remodeling in Lenke 1C scoliosis treated with
      selective thoracic fusion.
AB  - BACKGROUND CONTEXT: Selective thoracic fusion may cause spinal imbalance in
      certain patients; how the spinal alignment changes over time after surgery is
      highly correlated with the final spinal balance. PURPOSE: To investigate how
      spinal alignment changes over time after selective thoracic fusion and how spinal
      alignment remodeling affects spinal balance. METHODS: All adolescent idiopathic
      scoliosis (AIS) cases surgically treated in our institution between 2002 and 2008
      were reviewed. Inclusion criteria were as follows: Lenke 1C scoliosis patients
      treated with posterior pedicle screw-only constructs; the lowest instrumented
      vertebra (LIV) ended at L1 level or above; and 2-year radiographic follow-up.
      Standing anteroposterior and lateral digital radiographs from four different time
      points (preoperatively, immediately, 3 months, and 2 years postoperatively) were
      reviewed. In each standing anteroposterior radiograph, the center sacral vertical
      line (CSVL, the vertical line that bisects the proximal sacrum) was first drawn,
      and the translation (deviation from the CSVL) of some key vertebrae was measured,
      such as the LIV, LIV+1 (the first vertebra below LIV), LIV+2 (the second vertebra
      below LIV), LIV+3 (the third vertebra below LIV), lumbar apical vertebra (AV),
      thoracic AV, and T1. Additionally, the Cobb angles of the major thoracic and
      lumbar curves were measured at different time points, and the correction rates
      were calculated. Furthermore, clinical photographs of the patients from the back
      were taken preoperatively and postoperatively. RESULTS: Of 278 AIS patients
      reviewed, 29 met the inclusion criteria. The continuous follow-up of our present
      study revealed an interesting phenomenon: postoperative spinal alignment
      remodeling. A hypothetical criterion was established to determine the onset of
      the phenomenon. By means of a series of analyses, the criterion was validated.
      The results of our present study showed that selective thoracic fusion tended to
      cause leftward spinal imbalance in these Lenke 1C AIS patients. Twenty of the 29
      patients had leftward spinal imbalance immediately after surgery. Although some
      patients regained spinal balance through postoperative spinal alignment
      remodeling, 11 patients remained imbalanced at 2-year follow-up. CONCLUSIONS:
      Selective thoracic fusion is prone to cause leftward spinal imbalance in Lenke 1C
      scoliosis patients. Postoperative spinal alignment remodeling can facilitate
      recovery of spinal balance in some patients. Postoperative spinal imbalance in
      Lenke 1C scoliosis patients could be prevented by selecting stable vertebra or
      the vertebrae above as LIV, checking the balance condition during surgery, or
      considering ratio criteria when selecting candidates for selective thoracic
      fusion.

PMID- 22137605
TI  - Reciprocal regulation between AtNRT2.1 and AtAMT1.1 expression and the kinetics
      of NH(4)(+) and NO(3)(-) influxes.
AB  - Our results show that AtNRT2.1 expression has a positive effect on the NH(4)(+)
      ion influx, mediated by the HATS, as also occurs with AtAMT1.1 expression on the
      NO(3)(-) ion influx. AtNRT2.1 expression plays a key role in the regulation of
      AtAMT1.1 expression and in the NH(4)(+) ion influx, differentiating the nitrogen
      source, and particularly, the lack of it. Nitrogen starvation produces a
      compensatory effect by AtAMT1.1 when there is an absence of the AtNRT2.1 gene.
      Our results also show that, in the atnrt2 mutant lacking both AtNRT2.1 and
      AtNRT2.2, gene functions present different kinetic parameters on the NH(4)(+) ion
      influx mediated by the HATS, according to the source and availability of
      nitrogen. Finally, the absence of AMT1.1 also produces changes in the kinetic
      parameters of the NO(3)(-) influx, showing different V(max) values depending on
      the source of nitrogen available.

PMID- 22137606
TI  - Drought-responsive mechanisms in rice genotypes with contrasting drought
      tolerance during reproductive stage.
AB  - Water status is the main factor affecting rice production. In order to understand
      rice strategies in response to drought condition in the field, the drought
      responsive mechanisms at the physiological and molecular levels were studied in
      two rice genotypes with contrasting susceptibility to drought stress at
      reproductive stage. After 20 d of drought treatment, the osmotic potential of
      leaves reduced 78% and 8% in drought susceptible rice cultivar Zhenshan97B and
      tolerant rice cultivar IRAT109, respectively. The panicle lengths had no obvious
      changes in drought stressed Zhenshan97B and IRAT109, suggesting that drought
      stress impose less effect on assimilate translocation from leaf to vegetative
      growth of panicles. IRAT109 showed more extensive deeper root growth that could
      be considered a second line of defense against drought stress. The C(i)/C(a)
      ratio exhibited enhancement over reduction of g(s) in both cultivars, reflecting
      the non-stomatal limitation to photosynthesis occurred during drought stress.
      Orthophosphate dikinase, glycine dehydrogenase, ribulose bisphosphate carboxylase
      (Rubisco), glycine hydroxymethyltransferase and ATP synthase were down-regulated
      for Zhenshan97B in response to drought stress, suggesting the reduction of
      capacity of carbon assimilation in this rice cultivar. In drought-stressed
      IRAT109, transketolase, Rubisco were down-regulated, however, Rubisco activase
      and peptidyl-prolyl cis-trans isomerase, which might alleviate the damage on
      Rubisco by drought stress, were up-regulated. The increased abundances of
      chloroplastic superoxide dismutase [Cu-Zn] and dehydroascorbate reductase might
      provide antioxidant protection for IRAT109 against damage by dehydration.

PMID- 22137607
TI  - Two phenylalanine ammonia lyase isoforms are involved in the elicitor-induced
      response of rice to the fungal pathogen Magnaporthe oryzae.
AB  - Suspension cultured cells of a blast-resistant rice genotype (Oryza sativa L. cv.
      Gigante Vercelli) were treated with cell wall hydrolysates prepared from the
      fungal pathogen Magnaporthe oryzae. As a consequence, a complex pattern of
      phenylalanine ammonia lyase time course specific activity levels was evident. Ion
      exchange chromatographic fractionation of crude extracts suggested that the early
      (6 h) and the late (48-72 h after elicitation) increase of activity relied upon
      the sequential induction of two different isoenzymes. The relative expression
      levels of 11 genes putatively coding for a phenylalanine ammonia lyase were
      measured by semi-quantitative capillary gel electrophoresis of RT-PCR products.
      Two genes were indeed found to be induced by treatments with the hydrolysate, and
      data were validated by real-time PCR. Conversely, only the early-responsive
      enzyme form was observed following elicitation in a blast-sensitive rice genotype
      (cv. Vialone nano). Therefore, the late-responsive isoform may represent a
      candidate gene to select for decreased sensitivity to blast.

PMID- 22137608
TI  - Tipburn in salt-affected lettuce (Lactuca sativa L.) plants results from local
      oxidative stress.
AB  - Tipburn in lettuce is a physiological disorder expressed as a necrosis in the
      margins of young developing leaves and is commonly observed under saline
      conditions. Tipburn is usually attributed to Ca(2+) deficiencies, and there has
      very limited research on other mechanisms that may contribute to tipburn
      development. This work examines whether symptoms are mediated by increased
      reactive oxygen species (ROS) production. Two butter lettuce (Lactuca sativa L.)
      varieties, Sunstar (Su) and Pontina (Po), with contrasting tipburn susceptibility
      were grown in hydroponics with low Ca(2+) (0.5 mM), and with or without 50 mM
      NaCl. Tipburn symptoms were observed only in Su, and only in the saline
      treatment. Tipburn incidence in response to topical treatments with Ca(2+)
      scavengers, Ca(2+) transport inhibitors, and antioxidants was assessed. All
      treatments were applied before symptom expression, and evaluated later, when
      symptoms were expected to occur. Superoxide presence in tissues was determined
      with nitro blue tetrazolium (NBT) and oxidative damage as malondialdehyde (MDA)
      content. Superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase
      (APX) activities were assayed. Under control and saline conditions, tipburn could
      be induced in both varieties by topical treatments with a Ca(2+) scavenger (EGTA)
      and Ca(2+) transport inhibitors (verapamil, LaCl(3)) and reduced by supplying
      Ca(2+) along with a ionophore (A 23187). Tipburn symptoms were associated with
      locally produced ROS. O(2)(.-) and oxidative damage significantly increased in
      leaf margins before symptom expression, while topical antioxidant applications
      (Tiron, DPI) reduced symptoms in treated leaves, but not in the rest of the
      plant. Antioxidant enzyme activity was higher in Po, and increased more in
      response to EGTA treatments, and may contribute to mitigating oxidative damage
      and tipburn expression in this variety.

PMID- 22137609
TI  - [Integrated pharmaceutical care programme in patients with chronic diseases].
AB  - OBJECTIVES: To assess whether an integrated pharmaceutical care programme (IPCP)
      improves clinical evolution, patient quality of life, and reduces health costs in
      chronic patients. MATERIAL AND METHODS: A parallel, open, and multi-centre
      clinical trial of an IPCP in patients with heart failure (HF) and/or chronic
      obstructive pulmonary disease (COPD) in 8 different health areas in Cataluna. The
      intervened patient was monitored for pharmacotherapeutic evolution by hospital
      pharmacists, primary care physicians, and community pharmacists. Controls
      received normal follow-up. All patients were monitored for 12 months, with
      quality of life tests administered at the beginning and end of follow-up.
      RESULTS: We had the participation of 8 different hospitals, 8 primary care
      centres, and 109 community pharmacies. 238 patients completed the study, with
      2.9% of participants lost during the study period. There were no significant
      differences in terms of readmissions, visits to the doctors, or to emergency
      services. We detected 50 different medication-related problems (MRP) in 37
      patients, with a statistically significant difference in terms of MRP between the
      control and treatment groups of patients with HF, and almost significant
      differences in COPD patients. MRP were moderate-severe in 36% of cases. MRP were
      avoidable in 94% of cases, and the pharmacist resolved the issue in 90% of cases.
      There were no differences in terms of patient quality of life or health costs
      between the start and end of the study. CONCLUSIONS: Integrated pharmaceutical
      care programs facilitate an improvement in the quality of patient care, but
      electronic registries are necessary to promote communication between sections of
      the health care network.

PMID- 22137610
TI  - Therapeutic possibilities of interference RNA.

PMID- 22137611
TI  - [Effectiveness and safety of the FLAG-IDA regimen in acute refractory or
      recurrent leukaemia].
AB  - OBJECTIVE: To evaluate the effectiveness and safety of the FLAG-IDA regimen in
      patients with acute refractory and/or recurrent leukaemia. METHOD: Descriptive,
      retrospective, observational study of the clinical histories of patients with the
      FLAG-IDA regimen during the period of 2005-2010. Effectiveness was measured using
      objective response, progression-free interval, and global survival. Safety was
      measured using the NCI classification system of common toxicity criteria for
      adverse events. RESULTS: We registered 12 patients (52.17+/-8.26 years in women,
      and 54.83+/-7.22 years in men), 11 cases were acute myeloid leukaemia (5
      refractory, 3 in recurrence, 1 secondary to chronic refractory myeloid leukaemia
      (CML) and 2 secondary to myelodysplastic syndrome (MDS), one of which was
      refractory and the other had not been previously treated) and one case was acute
      refractory lymphoblastic leukaemia (ALL). Six patients (50%) reached a complete
      response (CR). One patient reached a partial response (PR), which was followed by
      another protocol that produced a CR, two died due to disease progression, and
      three due to secondary complications from treatment. The progression-free
      interval for patients that reached a CR was 24.38 weeks (6 months). Median global
      survival was 8.4 weeks. Mean time needed for the recovery of neutropenia was 23
      and 37 days in the first and second cycle, respectively. The mean time required
      for recuperation of thrombocytopenia was 24 and 35 days in each cycle.
      CONCLUSIONS: The FLAG-IDA induction regimen for the treatment of high-risk
      leukaemia patients is an established protocol, with good tolerance and acceptable
      toxicity levels that offers an opportunity for facilitating the transplantation
      of haematopoietic progenitors.

PMID- 22137612
TI  - Assessment of ablative margin by unenhanced magnetic resonance imaging after
      radiofrequency ablation for hepatocellular carcinoma.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of magnetic
      resonance imaging (MRI) without a contrast agent to visualize the ablative margin
      after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), compared
      with enhanced CT. METHODS: Twenty-five HCCs in 19 patients were treated by RFA.
      T1-weighted MRI was performed before and after RFA, and the signal intensities of
      the tumors and surrounding liver tissues were measured. Treatment efficacy was
      assessed based on three grades: margin (+), a continuous high-intensity rim
      around the index tumor; margin zero, a partially discontinuous high-intensity
      rim; margin (-), the tumor extends beyond the high-intensity rim. RESULTS: Twelve
      (86%) of fourteen low-intensity tumors on the pre-MRI were visualized as low
      intensity tumors on post-MRI, and the ablative margins were visualized as high
      intensity rims. Two (67%) of three high-intensity tumors on pre-MRI were
      visualized as higher-intensity tumors in the high-intensity ablative margin.
      Because the signal intensities of tumors and surrounding tissues in 14 tumors
      that were low- or high-intensity tumors on pre-MRI increased to the same extent,
      the tumors and ablative margin could be distinguished on post images. In 6 (75%)
      of the 8 iso-intensity tumors on pre-MRI, the ablative margin and tumor could
      also not be discriminated on post-MRI. The overall agreement between MRI and CT
      for the ablative margin was good (kappa coefficient=0.716, p=0.00002).
      CONCLUSION: In 82% of low- or high-intensity tumors on pre-MRI, post-MRI without
      a contrast agent enabled visualization of the ablative margin as a high-intensity
      rim, and it was possible to evaluate the ablative margin earlier and easier than
      with enhanced CT.

PMID- 22137613
TI  - Imaging features of small hepatocellular carcinomas with microvascular invasion
      on gadoxetic acid-enhanced MR imaging.
AB  - OBJECTIVES: Detection of hepatocellular carcinomas (HCCs) before microvascular
      invasion (MVI) occurs is important due to the poor outcomes associated with MVI.
      We retrospectively investigated the imaging features of small HCCs with MVI on
      gadoxetic acid-enhanced MR imaging. METHODS: Fifty patients (40 men and 10 women;
      mean age, 54 years) with 58 surgically proven small (2 cm or less) HCCs were
      evaluated by gadoxetic acid-enhanced MRI. Signal intensities on imaging sequences
      and the presence of the typical dynamic enhancement pattern (arterial enhancement
      and washout) were assessed. Fisher's exact tests were performed to evaluate the
      relationships between the presence of MVI, tumor size, and imaging findings.
      RESULTS: None of the 12 small HCCs with diameters of 1cm or less had MVI, while
      15 (33%) of the 46 small HCCs with diameters of 1.1-2.0 cm had MVI (p=0.025,
      Fisher's exact test). Among the small HCCs with diameters of 1.1-2.0 cm, all HCCs
      with MVI showed the typical dynamic pattern and hyperintensity on T2- and
      diffusion-weighted images. Most HCCs (54 lesions, 93%) were hypointense on
      hepatobiliary phase images regardless of the presence of MVI. CONCLUSIONS: All
      small HCCs with MVI showed typical dynamic pattern and hyperintensity on T2
      weighted and diffusion-weighted images, while atypical dynamic pattern and size
      of less than 1cm in diameter may suggest absence of MVI.

PMID- 22137614
TI  - Transcytosis of CRM197-grafted polybutylcyanoacrylate nanoparticles for
      delivering zidovudine across human brain-microvascular endothelial cells.
AB  - This study investigates the capability of CRM197-grafted polybutylcyanoacrylate
      (PBCA) nanoparticles (NPs) (CRM197/PBCA NPs) to carry zidovudine (AZT) across the
      blood-brain barrier (BBB). AZT was loaded on CRM197/PBCA NPs to traverse the
      monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by
      human astrocytes. The particle size distribution of AZT-loaded CRM197/PBCA NPs
      was quite uniform. In addition, AZT-loaded CRM197/PBCA NPs displayed a spherical
      shape with slightly fluffy exterior. The deposited thin film of AZT-loaded
      CRM197/PBCA NPs exhibited a hexagonal lattice-like geometry. When the diameter of
      AZT-loaded CRM197/PBCA NPs decreased, the loading efficiency of AZT on the drug
      carriers and the permeability coefficient of AZT across the BBB enhanced. An
      increase in the grafting quantity of CRM197 enhanced the permeability coefficient
      of AZT across the BBB and the uptake quantity of AZT-loaded CRM197/PBCA NPs by
      HBMECs. CRM197/PBCA NPs can be promising brain-targeting carriers for delivering
      AZT across the BBB.

PMID- 22137615
TI  - Diversity of microbes in amniotic fluid.
AB  - Recent polymerase chain reaction (PCR)-based studies estimate the prevalence of
      microbial invasion of the amniotic cavity (MIAC) to be >=30-50% higher than that
      detected by cultivation-based methods. Some species that have been long
      implicated in causing MIAC remain among the common invaders (e.g. Ureaplasma
      spp., Mycoplasma spp., Fusobacterium spp. Streptococcus spp., Bacteroides spp.
      and Prevotella spp.). Yet we now know from studies based on PCR of the 16S
      ribosomal DNA that cultivation-resistant anaerobes belonging to the family
      Fusobacteriaceae (particularly Sneathia sanguinegens, and Leptotrichia spp.) are
      also commonly found in amniotic fluid. Other diverse microbes detected by PCR of
      amniotic fluid include as-yet uncultivated and uncharacterized species. The
      presence of some microbial taxa is associated with specific host factors (e.g.
      Candida spp. and an indwelling intrauterine device). It appears that MIAC is
      polymicrobial in 24-67% of cases, but the potential role of pathogen synergy is
      poorly understood. A causal relationship between diverse microbes, as detected by
      PCR, and preterm birth is supported by types of association (e.g. space, time and
      dose) proposed as alternatives to Koch's postulates for inferring causality from
      molecular findings. The microbial census of the amniotic cavity remains
      unfinished. A more complete understanding may inform future research directions
      leading to improved strategies for preventing, diagnosing and treating MIAC.

PMID- 22137616
TI  - [Moderate-to-severe psoriasis: from recommendations to practical procedures;
      optimizing day-to-day management in actual practice].

PMID- 22137617
TI  - [Psoriasis: Practical pre-therapeutic assessment].
AB  - Psoriasis is a chronic disease for which treatment is not definitive and is
      likely to vary over time. A number of parameters must be taken into consideration
      for the initial assessment of psoriasis patients requiring systemic therapy, with
      the latter being based primarily on the previous drug history, objective medical
      evaluation of the psoriasis and comorbidities, and determination of any medical
      contraindications to the various treatments available. However, social factors,
      the patient's lifestyle, level of understanding and compliance, as well as
      various economic factors must also be borne in mind when deciding upon a
      therapeutic approach. A complete dossier setting out the patient's drug history
      and disease history forms the key reference and is essential for treatment
      monitoring and adjustment, reflecting changes in the course of the skin disease
      and in the patient's medical history. This information must be made available to
      all doctors involved in the patient's treatment in order to ensure optimal
      management.

PMID- 22137618
TI  - [Choice of therapy based on clinical setting].
AB  - The choice of therapy in psoriasis is a complex multidimensional process based on
      both patient-related and disease-related factors. Standardisation of inclusion
      criteria for clinical trials leads to the exclusion of large numbers of patients
      with special forms of psoriasis or presenting comorbidities that must
      nevertheless be dealt with in real-life situations. The main patient-related
      factors affecting choice of therapy are age, pregnancy for women and the desire
      to father children for men, renal and hepatic failure, the risk of infection and
      neoplasia, metabolic and both cardiovascular and psychiatric comorbidities, as
      well as compliance and lifestyle. Disease-related factors affecting choice of
      therapy include unstable lesions, acral sites (palms, soles, nails, face and
      scalp), erythrodermic psoriasis, pustular psoriasis, guttate psoriasis and
      associated psoriatic rheumatism. The therapeutic recommendations set out in this
      study are based upon a critical analysis of the literature and upon the actual
      therapeutic practice of the experts.

PMID- 22137619
TI  - [Phototherapy for psoriasis].

PMID- 22137620
TI  - [Acitretin].

PMID- 22137621
TI  - [Methotrexate].

PMID- 22137622
TI  - [Cyclosporine].

PMID- 22137623
TI  - [Infliximab].

PMID- 22137624
TI  - [Adalimumab].

PMID- 22137625
TI  - [Etanercept].

PMID- 22137626
TI  - [Ustekinumab].

PMID- 22137627
TI  - [Organising the follow-up of biologics].
AB  - Treatment with biologics requires specific evaluation based on assessment of
      clinical efficacy, of comorbidities and of safety. Although evaluation is mainly
      clinical, additional laboratory investigations may be needed. The occurrence of
      events, whether disease-related (infection, dysimmunity, cancer) or not
      (pregnancy, vaccination), is described in specific guidelines and in notification
      reports submitted to pharmacovigilance agencies.

PMID- 22137628
TI  - [Organisation of combined follow-up by hospitals and private dermatologists].
AB  - Systemic therapy of psoriasis with biologics or cyclosporine requires combined
      follow-up of patients by hospitals and dermatologists in private practice.
      Initiation of therapy and the laboratory examinations required before starting
      treatment are carried out in a hospital setting, and subsequent follow-up may be
      carried out by a dermatologist in private practice. Successful combined follow-up
      depends on certain key points, chiefly good knowledge by the independent
      dermatologist of the systemic therapies available for psoriasis, and smooth
      working of the hospital-dermatologist interface. It is essential to develop
      training and information tools in order to optimise joint therapy. This may also
      be formalised by the creation of a healthcare network as provided for in French
      legislation (law of 4 March 2002).

PMID- 22137629
TI  - [Patient education. Information letter on UVB phototherapy].

PMID- 22137630
TI  - [Patient education. Information letter on PUVA phototherapy].

PMID- 22137631
TI  - [Patient education. Information letter on treatment of psoriasis with
      methotrexate].

PMID- 22137632
TI  - [Patient education. Information letter on treatment of psoriasis with oral
      cyclosporine].

PMID- 22137633
TI  - [Patient education. Information letter on treatment of psoriasis with infliximab
      (Remicade)].

PMID- 22137634
TI  - [Patient education. Information letter on treatment of psoriasis with adalimumab
      (Humira)].

PMID- 22137635
TI  - [Patient education. Information letter on treatment of psoriasis with etanercept
      (Enbrel)].

PMID- 22137636
TI  - [Patient education. Information letter on treatment of psoriasis with ustekinumab
      (Stelara)].

PMID- 22137637
TI  - Q-fever can simulate a lupus flare.
AB  - Fever is a diagnostic challenge in the patient with lupus. Infections can mimic a
      lupus flare which further complicates the diagnostic approach. Moreover,
      immunosuppressive treatment of SLE may promote the development of infections and
      poor outcome. We report the case of a patient with SLE with an initial diagnosis
      of lupus flare, who was found to have Q fever showing an excellent response to
      treatment with doxycycline.

PMID- 22137638
TI  - Prenatal diagnosis and management of a craniofacial glioma detected at 20 weeks'
      gestation. Case report and review of the literature.
AB  - Foetal imaging and anomaly detection is advancing at a rapid rate. As a result,
      detection of foetal craniofacial abnormalities is increasing. Ultrasound and
      magnetic resonance imaging are currently the imaging modalities most commonly
      used. The authors describe the detection of a nasal glioma at 20 weeks'
      gestation, subsequent prenatal monitoring and postnatal management with surgical
      excision at 2 months of age. The world literature regarding prenatal diagnosis
      and management of craniofacial malformations is discussed.

PMID- 22137639
TI  - Role of molecular imaging in stem cell therapy for myocardial restoration.
AB  - During the past two decades, stem cells have created enthusiasm as a regenerative
      therapy for ischemic heart disease. Transplantation of bone marrow stem cells,
      skeletal myoblasts, and endothelial progenitor cells has shown to improve
      myocardial function after infarction. Recently, attention has focused on the
      potential use of embryonic stem cells and induced pluripotent stem cells because
      they possess the capacity to differentiate into various cell types, including
      cardiac and endothelial cells. Clinical trials have shown positive effects on the
      functional recovery of heart after myocardial infarction and have answered
      questions on timing, dosage, and cell delivery route of stem cells such as those
      derived from bone marrow. Despite the current advances in stem cell research, one
      main hurdle remains the lack of reliable information about the fate of cell
      engraftment, survival, and proliferation after transplantation. This review
      discusses the different cell types used in cardiac cell therapy as well as
      molecular imaging modalities relevant to survival issues.

PMID- 22137641
TI  - Pre-participation examination of competitive athletes: role of the ECG.
AB  - Sudden cardiac death in athletes is rare but has a wide social impact because it
      confronts the general population with the paradox that athletes perceived and
      admired as the fittest and healthiest suddenly drop dead during their sport. Mass
      media coverage is guaranteed in the case of sudden cardiac death of a top
      athlete, while other competitive and noncompetitive athletes of all ages, team
      members, sponsors, as well as huge parts of society remain puzzled and
      frightened. Therefore, debate is ongoing regarding how to minimize the number of
      fatalities, and the search continues for a cost-effective preparticipation
      screening for competitive athletes. Despite the fact that routine ECG screening
      would be widely available and rather inexpensive, debate continues regarding
      whether this should be part of initial screening for every athlete before
      starting to train at high intensity as well as during annual checkups. The role
      of ECGs in preparticipation examinations of competitive athletes is intensively
      discussed because there is a lack of strict criteria for which ECG findings
      should generate further workup. In this article, we analyze the main publications
      on sudden cardiac death, focusing on the benefit of ECG screening in
      preparticipation examination as it has been shown to be feasible and effective in
      identifying athletes at risk of sudden cardiac death.

PMID- 22137640
TI  - Cardiovascular biology of microsomal prostaglandin E synthase-1.
AB  - Both traditional and purpose-designed nonsteroidal anti-inflammatory drugs,
      selective for inhibition of cyclooxygenase (COX)-2, alleviate pain and
      inflammation but confer a cardiovascular hazard attributable to inhibition of COX
      2-derived prostacyclin (PGI(2)). Deletion of microsomal PGE synthase-1 (mPGES-1),
      the dominant enzyme that converts the COX-derived intermediate product PGH(2) to
      PGE(2), modulates inflammatory pain in rodents. In contrast with COX-2 deletion
      or inhibition, PGI(2) formation is augmented in mPGES-1(-/-) mice-an effect that
      may confer cardiovascular benefit but may undermine the analgesic potential of
      inhibitors of this enzyme. This review considers the cardiovascular biology of
      mPGES1 and the complex challenge of developing inhibitors of this enzyme.

PMID- 22137642
TI  - Regulation and differential role of the tissue factor isoforms in cardiovascular
      biology.
AB  - Alternative pre-mRNA splicing is an essential mechanism regulating protein
      diversity and functional plasticity of the proteome in response to environmental
      changes. Several factors are involved in this regulatory mechanism, such as
      serine/arginine-rich (SR) proteins, the Cdc2-like kinase (Clk) family, the dual
      specificity tyrosine phosphorylation regulated kinases, the SR protein kinases
      (SRPK) 1 and 2, the protein kinase B (PKB,Akt), and the DNA topoisomerase I (DNA
      topo I). Dynamic changes of the phosphorylation state of SR proteins, mediated by
      the kinases mentioned previously, play an important role in alternative splicing
      regulation. Through alternative splicing of the tissue factor (TF) pre-mRNA, two
      naturally occurring forms of TF, the primary initiator of blood coagulation, are
      expressed in humans-soluble alternatively spliced (as)TF and membrane-bound "full
      length" (fl)TF. Both isoforms are known to circulate in blood. flTF, rather than
      asTF, appears to be the major contributor to the thrombogenicity of vascular wall
      and blood. asTF has been linked more closely to increased cell survival and
      angiogenesis. We found the expression of asTF and flTF to be reduced in the
      myocardium of patients with dilated cardiomyopathy, indicating a role of TF in
      maintaining myocardial structure. Moreover, we demonstrated proinflammatory
      cytokines to immediately upregulate the expression of both TF isoforms, which was
      differentially regulated by SR proteins as well as Clks and DNA topo I. We and
      others have shown that asTF induces cell proliferation, survival, and
      angiogenesis via signaling pathways different from flTF-induced effects. These
      data indicate that both TF isoforms influence diverse processes in cardiovascular
      (patho)biology and are potential targets for antithrombotic, pro-survival, and
      proangiogenic therapeutic strategies.

PMID- 22137643
TI  - CXCL12: a new player in coronary disease identified through human genetics.
AB  - Genome-wide association studies (GWAS) of more than 100,000 people have revealed
      novel loci associated with coronary artery disease and myocardial infarction that
      present exciting opportunities to discover novel disease pathways. One such
      recently identified locus is on chromosome 10q11, near the gene for the chemokine
      CXCL12, which has been implicated in cardiovascular disease in both mouse and
      human studies. These GWAS demonstrate that CXCL12 may emerge as a potential
      therapeutic target for atherosclerosis and thrombosis.

PMID- 22137644
TI  - Introduction to DSM-5 criteria linked papers in drug and alcohol dependence.
AB  - The DSM-5 Substance Use Disorders (SUD) Workgroup has considered a number of
      issues in the process of implementing revisions designed to result in better
      definitions of the disorders. One of the main issues considered was what to do
      about the DSM-IV division between two disorders, abuse and dependence. This issue
      arose because the reliability and validity of abuse was far lower and more
      variable than the reliability and validity of dependence, and also because
      misconceptions regarding the relationship of abuse to dependence abound among
      clinicians and researchers. Additional issues the SUD workgroup considered
      included whether to add new criteria, e.g., craving, and remove existing
      criteria, e.g. legal problems. Some issues pertaining to gambling disorders were
      considered as well.

PMID- 22137645
TI  - The association between alcohol use and hepatitis C status among injecting drug
      users in Glasgow.
AB  - BACKGROUND: We investigated the association between actual and self-reported
      hepatitis C virus (HCV) status and alcohol consumption among injecting drug users
      (IDUs) to determine whether IDUs who self-report as HCV infected comply with UK
      guidelines on safe drinking and to determine risk factors for drinking. METHODS:
      We conducted a repeat cross-sectional survey of IDUs accessing harm reduction
      services in Glasgow in 2005 and 2007. We measured self-reported weekly alcohol
      consumption, excess drinking (defined as exceeding the UK Royal College of
      Physician's guidelines for safe drinking of 14 units/week for women and 21
      units/week for men) and HCV antibodies (anonymously in oral fluid). RESULTS:
      Among IDUs who tested HCV antibody positive, 65% drank alcohol and 29% drank to
      excess, compared to 61% (p=0.3) and 18% (p<0.001) of those who tested negative,
      respectively. IDUs who self-reported as HCV positive were less likely to drink
      but as likely to drink to excess as self-reported negatives or those with HCV
      status unknown, both among all IDUs and those who tested HCV antibody positive.
      Among the antibody positives, excess drinking was associated with incarceration
      (aOR=2.56; 95% CI: 1.28-5.12), homelessness within six months of interview
      (aOR=3.60; 95% CI: 2.00-6.48) and homelessness more than six months before
      interview (aOR=1.93; 95% CI: 1.06-3.53). CONCLUSIONS: IDUs who believe they are
      HCV infected are more likely to abstain from alcohol, but those who drink
      continue to do so to excess. IDUs diagnosed with HCV need greater support to
      reduce their alcohol consumption.

PMID- 22137647
TI  - [Chronic obstructive pulmonary disease in the elderly: next phenotype].

PMID- 22137646
TI  - Motivational assessment of non-treatment buprenorphine research participation in
      heroin dependent individuals.
AB  - BACKGROUND: Heroin abuse remains an important public health problem, particularly
      in economically disadvantaged areas. Insight into this problem is gained from
      interviewing addicted individuals. However, we lack systematic data on factors
      that motivate heroin users to participate in non-treatment research that offers
      both financial incentives (compensation) and non-financial incentives (e.g.,
      short-term medication). AIM: To better understand the relative importance of
      several types of personal motivations to participate in non-treatment
      buprenorphine research, and to relate self-motivations to social, economic,
      demographic and drug use factors. METHODS: Heroin dependent volunteers (N=235
      total; 57 female and 178 male; 136 African American, 86 Caucasian, and 13 Other)
      applied for non-therapeutic buprenorphine research in an urban outpatient setting
      from 2004 to 2008. We conducted a semi-structured behavioral economic interview,
      after which participants ranked 11 possible motivations for research
      participation. RESULTS: Although the study was repeatedly described as non
      treatment research involving buprenorphine, participants often ranked some
      treatment-related motivations as important (wanting to reduce/stop heroin use,
      needing a medication to get stabilized/detoxify). Some motivations correlated
      with income, heroin use, and years since marketing of buprenorphine. Two
      dimensions emerged from principal component analysis of motivation rankings: (1)
      treatment motivation vs. greater immediate needs and (2) commitment to trying
      alternatives vs. a more accepting attitude toward traditional interventions. In
      summary, heroin addicts' self-motivations to engage in non-therapeutic research
      are complex--they value economic gain but not exclusively or primarily--and
      relate to variables such as socioeconomic factors and drug use.

PMID- 22137648
TI  - A new FSA approach for in situ gamma ray spectroscopy.
AB  - An increasing demand of environmental radioactivity monitoring comes both from
      the scientific community and from the society. This requires accurate, reliable
      and fast response preferably from portable radiation detectors. Thanks to recent
      improvements in the technology, gamma spectroscopy with sodium iodide
      scintillators has been proved to be an excellent tool for in-situ measurements
      for the identification and quantitative determination of gamma ray emitting
      radioisotopes, reducing time and costs. Both for geological and civil purposes
      not only (40)K, (238)U, and (232)Th have to be measured, but there is also a
      growing interest to determine the abundances of anthropic elements, like (137)Cs
      and (131)I, which are used to monitor the effect of nuclear accidents or other
      human activities. The Full Spectrum Analysis (FSA) approach has been chosen to
      analyze the gamma spectra. The Non Negative Least Square (NNLS) and the energy
      calibration adjustment have been implemented in this method for the first time in
      order to correct the intrinsic problem related with the chi(2) minimization which
      could lead to artifacts and non physical results in the analysis. A new
      calibration procedure has been developed for the FSA method by using in situ
      gamma spectra instead of calibration pad spectra. Finally, the new method has
      been validated by acquiring gamma spectra with a 10.16 cm * 10.16 cm sodium
      iodide detector in 80 different sites in the Ombrone basin, in Tuscany. The
      results from the FSA method have been compared with the laboratory measurements
      by using HPGe detectors on soil samples collected particular, the (137)Cs
      isotopes has been implemented in the analysis since it has been found not
      negligible during the in-situ measurements.

PMID- 22137649
TI  - Health impact assessment and monetary valuation of IQ loss in pre-school children
      due to lead exposure through locally produced food.
AB  - A case study has been performed which involved the full chain assessment from
      policy drivers to health effect quantification of lead exposure through locally
      produced food on loss of IQ in pre-school children at the population level across
      the EU-27, including monetary valuation of the estimated health impact. Main
      policy scenarios cover the period from 2000 to 2020 and include the most
      important Community policy developments expected to affect the environmental
      release of lead (Pb) and corresponding human exposure patterns. Three distinct
      scenarios were explored: the emission situation based on 2000 data, a business-as
      usual scenario (BAU) up to 2010 and 2020 and a scenario incorporating the most
      likely technological change expected (Most Feasible Technical Reductions, MFTR)
      in response to current and future legislation. Consecutive model calculations
      (MSCE-HM, WATSON, XtraFOOD, IEUBK) were performed by different partners on the
      project as part of the full chain approach to derive estimates of blood lead (B
      Pb) levels in children as a consequence of the consumption of local produce. The
      estimated B-Pb levels were translated into an average loss of IQ points/child
      using an empirical relationship based on a meta-analysis performed by Schwartz
      (1994). The calculated losses in IQ points were subsequently further translated
      into the average cost/child using a cost estimate of ?10.000 per loss of IQ point
      based on data from a literature review. The estimated average reduction of
      cost/child (%) for all countries considered in 2010 under BAU and MFTR are 12.16
      and 18.08% as compared to base line conditions, respectively. In 2020 the
      percentages amount to 20.19 and 23.39%. The case study provides an example of the
      full-chain impact pathway approach taking into account all foreseeable pathways
      both for assessing the environmental fate and the associated human exposure and
      the mode of toxic action to arrive at quantitative estimates of health impacts at
      the individual and the population risk levels alike at EU scale. As the estimated
      B-Pb levels fall below the range of observed biomonitoring data collected for pre
      school children in 6 different EU countries, results presented in this paper are
      only a first approximation of the costs entailed in the health effects of
      exposure to lead and the potential benefits that may arise from MFTR measures
      inscribed in Commission policies.

PMID- 22137650
TI  - Assessment of mercury and selenium concentrations in captive bottlenose dolphin's
      (Tursiops truncatus) diet fish, blood, and tissue.
AB  - Concentrations of total mercury (Hg) and selenium (Se) were determined in diet
      fish and whole blood and tissue samples from seven bottlenose dolphins (Tursiops
      truncatus) housed at the National Aquarium Baltimore (NAB). In addition,
      concentrations of monomethylmercury (CH(3)Hg(+)) were determined in diet fish and
      dolphins' tissue samples. The data were compared with the values found in wild
      populations to better understand how the dietary Hg and Se uptake rates affect
      the Hg and Se levels in dolphins. The diet fish total Hg concentrations ranged
      between 14 and 47 ng g(-1) and were markedly lower than for similar fish found in
      Florida, South Carolina, and other aquaria. CH(3)Hg(+) accounted for 85 to 91% of
      the total Hg found in diet fish. The diet fish Se concentrations ranged between
      270 and 800 ng g(-1), indicating excess molar concentrations of Se over Hg. The
      Hg concentration range in the blood of NAB dolphins was 27-117 ng g(-1) and the
      concentrations were about one order of magnitude and several factors lower than
      the concentrations found in the blood of wild bottlenose dolphins in Florida and
      in South Carolina, respectively. The total Hg and CH(3)Hg(+) in tissue samples
      were also significantly lower than the reported values obtained from wild
      populations of bottlenose dolphins. The differences in the Hg concentrations in
      the dolphins' blood may be due to the different levels of Hg atmospheric
      deposition in the area where the dolphins' diet fish were found. The Se
      concentration range in the blood of NAB dolphins was 221-297 ng g(-1) which was
      two factors lower than the values found in wild populations. The lower Hg levels,
      as well as higher Se:Hg molar ratios in the blood of NAB dolphins, suggest that
      NAB dolphins may be less susceptible to the potential neurotoxicity from the
      CH(3)Hg(+) in their blood.

PMID- 22137651
TI  - Nicotine occurrence in bottled mineral water: analysis of 10 brands of water in
      Spain.
AB  - The presence of pharmaceuticals in surface and drinking water has been evidenced
      in numerous studies. Despite representing one of the most common consumption
      sources, to the best of our knowledge, this is the first report on the presence
      of pharmaceutical compounds in bottled mineral water. Pollution of these sources
      not only could pose a serious human health risk, but would also warn about the
      quality of the water in our aquifers, a vital and vulnerable source of water,
      essential for the future water supply. Fifty eight pharmaceutically active
      compounds (PhACs) belonging to the 12 main therapeutic groups were analyzed in 10
      bottled mineral water brands produced in Spain. Nicotine was detected in
      concentrations ranging from 7ngL(-1) to 15ngL(-1) in 5 of 10 bottled mineral
      waters. Despite the low nicotine concentration measured, the presence of this
      compound in bottled water still raises concern. Health risk assessment
      researchers have postulated that the risk to adult healthy humans from oral
      intake of nicotine at low levels is negligible. However, no studies have been
      conducted to assess the human health risk of vulnerable populations such as
      pregnant women and newborns. This population is the target of advertising on the
      purity and quality characteristics of bottled mineral water.

PMID- 22137652
TI  - High concentrations of cadmium, cerium and lanthanum in indoor air due to
      environmental tobacco smoke.
AB  - BACKGROUND: Environmental tobacco smoke (ETS) is one of the most important
      sources for indoor air pollution and a substantial threat to human health, but
      data on the concentrations of the trace metals cerium (Ce) and lanthanum (La) in
      context with ETS exposure are scarce. Therefore the aim of our study was to
      quantify Ce and La concentrations in indoor air with high ETS load. METHODS: In
      two subsequent investigations Ce, La and cadmium (Cd) in 3 smokers' (11 samples)
      and 7 non-smokers' (28 samples) households as well as in 28 hospitality venues in
      Southern Germany were analysed. Active sampling of indoor air was conducted
      continuously for seven days in every season in the smokers' and non-smokers'
      residences, and for 4h during the main visiting hours in the hospitality venues
      (restaurants, pubs, and discotheques). RESULTS: In terms of residences median
      levels of Cd were 0.1 ng/m(3) for non-smokers' and 0.8 ng/m(3) for smokers'
      households. Median concentrations of Ce were 0.4 ng/m(3) and 9.6 ng/m(3), and
      median concentrations of La were 0.2 ng/m(3) and 5.9 ng/m(3) for non-smokers' and
      for smokers' households, respectively. In the different types of hospitality
      venues median levels ranged from 2.6 to 9.7 ng/m(3) for Cd, from 18.5 to 50.0
      ng/m(3) for Ce and from 10.6 to 23.0 ng/m(3) for La with highest median levels in
      discotheques. CONCLUSIONS: The high concentrations of Ce and La found in ETS
      enriched indoor air of smokers' households and hospitality venues are an
      important finding as Ce and La are associated with adverse health effects and
      data on this issue are scarce. Further research on their toxicological, human and
      public health consequences is urgently required.

PMID- 22137653
TI  - Fluorophilia: fluorophore-containing compounds adhere non-specifically to injured
      neurons.
AB  - Ionic (free) zinc (Zn(2+)) is implicated in apoptotic neuronal degeneration and
      death. In our attempt to examine the effects of Zn(2+) in neurodegeneration
      following brain injury, we serendipitously discovered that injured neurons bind
      fluorescein moieties, either alone or as part of an indicator dye, in histologic
      sections. This phenomenon, that we have termed "fluorophilia", is analogous to
      the ability of degenerating neuronal somata and axons to bind silver ions
      (argyrophilia - the basis of silver degeneration stains). To provide evidence
      that fluorophilia occurs in sections of brain tissue, we used a wide variety of
      indicators such as Fluoro-Jade (FJ), a slightly modified fluorescein sold as a
      marker for degenerating neurons; Newport Green, a fluorescein-containing Zn(2+)
      probe; Rhod-5N, a rhodamine-containing Ca(2+) probe; and plain fluorescein. All
      yielded remarkably similar staining of degenerating neurons in the traumatic
      brain-injured tissue with the absence of staining in our sham-injured brains.
      Staining of presumptive injured neurons by these agents was not modified when
      Zn(2+) in the brain section was removed by prior chelation with EDTA or TPEN,
      whereas staining by a non-fluorescein containing Zn(2+) probe, N-(6-methoxy-8
      quinolyl)-p-toluenesulfonamide (TSQ), was suppressed by prior chelation. Thus,
      certain fluorophore-containing compounds nonspecifically stain degenerating
      neuronal tissue in histologic sections and may not reflect the presence of
      Zn(2+). This may be of concern to researchers using indicator dyes to detect
      metals in brain tissue sections. Further experiments may be advised to clarify
      whether Zn(2+)-binding dyes bind more specifically in intact neurons in culture
      or organotypic slices.

PMID- 22137654
TI  - Region-specific changes in the immunoreactivity of SIRT1 expression in the
      central nervous system of SOD1(G93A) transgenic mice as an in vivo model of
      amyotrophic lateral sclerosis.
AB  - SIRT1, which is a mammalian homolog of yeast nicotinamide adenine dinucleotide
      dependent deacetylase silent information regulator 2 (SIR2), is the best
      characterized SIRT family member. SIRT1 regulates longevity in several model
      organisms and is involved in several processes in mammalian cells, including cell
      survival, differentiation, and metabolism. In the present study, we used
      SOD1(G93A) mutant transgenic mice as an in vivo model of amyotrophic lateral
      sclerosis (ALS) and performed immunohistochemical studies, RT-PCR and western
      blotting analysis in order to investigate the changes of SIRT1 immunoreactivity
      in the central nervous system of these mice. An increased expression of SIRT1 was
      obvious in the cerebral cortex, hippocampal formation, thalamus and spinal cord
      of symptomatic SOD1(G93A) transgenic mice. In the cerebral cortex, SIRT1
      immunoreactivity was significantly increased in pyramidal cells of SOD1(G93A)
      transgenic mice. In the hippocampal formation of these mice, SIRT1
      immunoreactivity was increased in the pyramidal cells of the CA1-3 areas and in
      the granule cells of the dentate gyrus. In addition, SIRT1 immunoreactivity was
      increased in the spinal cord and thalamus of symptomatic SOD1(G93A) transgenic
      mice. This study, which showed increased SIRT1 in different brain regions of
      SOD1(G93A) transgenic mice, may provide clues to the understanding of selective
      neuronal loss in ALS. These findings suggest a role for SIRT1 in the motor
      functions in ALS but the mechanisms and functional implications of increased
      SIRT1 require elucidation.

PMID- 22137655
TI  - PI 3-kinase and PKCzeta mediate insulin-induced potentiation of NMDA receptor
      currents in Xenopus oocytes.
AB  - Insulin modulates N-methyl-d-aspartate (NMDA) receptors in the CNS and
      potentiates recombinant NMDA receptor currents in Xenopus oocytes. We have
      previously found that insulin's potentiation of NMDA receptor currents in oocytes
      occurs in a subunit specific manner and via phosphorylation of specific C
      terminal sites by protein tyrosine kinases (PTKs) and C-type protein kinases
      (PKCs). Insulin-mediated current potentiation of receptors containing the NR2A
      subunit occurs solely through the activation of PKCs. Activation of
      phosphoinositide 3-kinase (PI 3-kinase) is known to trigger many insulin
      stimulated signaling pathways, and we show here that it lies at a critical step
      in the insulin-mediated potentiation of NMDA receptor currents. Incubation with
      the PI 3-kinase inhibitor wortmannin eliminates insulin potentiation of NMDA
      receptor currents in the oocytes. Atypical isoforms of PKC are known to be
      activated downstream in the insulin signaling pathway via activation of PI 3
      kinase. We demonstrate that the atypical isoform PKC zeta (PKCzeta) has a role in
      insulin-stimulated current potentiation of NR2A-containing NMDA receptors using
      an isoform-specific pseudosubstrate inhibitor of PKCzeta.

PMID- 22137656
TI  - Ibudilast, a phosphodiesterase inhibitor with anti-inflammatory activity,
      protects against ischemic brain injury in rats.
AB  - Ibudilast, a non-selective phosphodiesterase inhibitor, is clinically used in
      patients with stroke or dizziness. However, whether the compound exerts a
      beneficial effect on acute ischemic stroke remains to be established. We used a
      rat model of transient focal cerebral ischemia using middle cerebral artery
      occlusion (MCAO) and reperfusion, and explored the effects of ibudilast on
      infarction size, brain edema, atrophy, and nerve cell death. Neurological
      outcomes (behavior and mortality) of rats were also assessed. An intravenous
      administration of ibudilast attenuated the size of cerebral infarction in a dose
      dependent manner, with the most significant reduction achieved at the dose of
      10mg/kg. Ibudilast induced a significant reduction in infarct size when
      administered 30min before MCAO or 0-2h after reperfusion, with the largest
      reduction observed at 30min before MCAO and 1h after reperfusion. Ibudilast
      significantly attenuated brain edema formation, cerebral atrophy and apoptosis of
      nerve cells preferentially in the cortical penumbra area, and also significantly
      reduced mortality and improved neurological outcomes. Expression of various
      inflammatory mediator molecules in both hemispheres was markedly suppressed by
      ibudilast. We conclude that ibudilast exerts beneficial effects against acute
      brain ischemia in an animal model.

PMID- 22137657
TI  - Involvement of the long-chain fatty acid receptor GPR40 as a novel pain
      regulatory system.
AB  - G-protein receptor (GPR) 40 is known to be activated by docosahexaenoic acid
      (DHA). However, reports studying the role and functions (including pain
      regulation) of GPR40 in the brain are lacking. We investigated the involvement of
      GPR40 in the brain on DHA-induced antinociceptive effects. Expression of GPR40
      protein was observed in the olfactory bulb, striatum, hippocampus, midbrain,
      hypothalamus, medulla oblongata, cerebellum and cerebral cortex in the brain as
      well as the spinal cord, whereas GPR120 protein expression in these areas was not
      observed. Intracerebroventricular (i.c.v.), but not intrathecal (i.t.) injection
      of DHA (25 and 50MUg/mouse) and GW9508 (a GPR40- and GPR120-selective agonist;
      0.1 and 1.0MUg/mouse) significantly reduced formalin-induced pain behavior. These
      effects were inhibited by pretreatment with the MU opioid receptor antagonist
      beta-funaltrexamine (beta-FNA), naltrindole (delta opioid receptor antagonist)
      and anti-beta-endorphin antiserum. The kappa opioid receptor antagonist
      norbinaltorphimine (nor-BNI) did not affect the antinociception of DHA or GW9508.
      Furthermore, the immunoreactivity of beta-endorphin in the hypothalamus increased
      at 10 and 20min after i.c.v. injection of DHA and GW9508. These findings suggest
      that DHA-induced antinociception via beta-endorphin release may be mediated (at
      least in part) through GPR40 signaling in the supraspinal area, and may provide
      valuable information on a novel therapeutic approach for pain control.

PMID- 22137659
TI  - Evaluating underlying neuronal activity associated with escape/avoidance behavior
      in response to noxious stimulation in adult rats.
AB  - The place escape/avoidance paradigm (PEAP) is a behavioral test designed to
      quantify the level of unpleasantness evoked by painful stimuli by assessing the
      willingness of a subject to escape/avoid a preferred area when it is associated
      with noxious stimulation. Previous studies have demonstrated that
      escape/avoidance behavior is dependent on activity in the anterior cingulate
      cortex (ACC), a region of the limbic system involved in processing the emotional
      component of pain in humans and animals. Analysis of c-Fos expression in the ACC
      confirmed that the escape/avoidance response to noxious stimuli corresponds to
      changes in neural activation in this region. Behavioral tests such as the PEAP
      may be more sensitive to changes in supraspinal pain processing and could
      contribute to the development of novel analgesics in the future.

PMID- 22137660
TI  - Segmentation of synchrotron radiation micro-computed tomography images using
      energy minimization via graph cuts.
AB  - The research on applications of segmentation algorithms to Synchrotron Radiation
      X-Ray micro-Computed Tomography (SR-MUCT) is an open problem, due to the
      interesting and well-known characteristics of SR images, such as the phase
      contrast effect. The Energy Minimization via Graph Cuts (EMvGC) algorithm
      represents state-of-art segmentation algorithm, presenting an enormous potential
      of application in SR-MUCT imaging. We describe the application of the algorithm
      EMvGC with swap move for the segmentation of bone images acquired at the ELETTRA
      Laboratory (Trieste, Italy).

PMID- 22137658
TI  - Isoflurane/nitrous oxide anesthesia induces increases in NMDA receptor subunit
      NR2B protein expression in the aged rat brain.
AB  - Postoperative cognitive dysfunction, POCD, afflicts a large number of elderly
      surgical patients following surgery with general anesthesia. Mechanisms of POCD
      remain unclear. N-methyl-D-aspartate (NMDA) receptors, critical in learning and
      memory, that display protein expression changes with age are modulated by
      inhalation anesthetics. The aim of this study was to identify protein expression
      changes in NMDA receptor subunits and downstream signaling pathways in aged rats
      that demonstrated anesthesia-induced spatial learning impairments. Three-month
      old and 18-month-old male Fischer 344 rats were randomly assigned to receive 1.8%
      isoflurane/70% nitrous oxide (N(2)O) anesthesia for 4h or no anesthesia. Spatial
      learning was assessed at 2weeks and 3months post-anesthesia in Morris water maze.
      Hippocampal and cortical protein lysates of 18-month-old rats were immunoblotted
      for activated caspase 3, NMDA receptor subunits, and extracellular-signal
      regulated kinase (ERK) 1/2. In a separate experiment, Ro 25-6981 (0.5mg/kg dose)
      was administered by I.P. injection before anesthesia to 18-month-old rats.
      Immunoblotting of NR2B was performed on hippocampal protein lysates. At 3months
      post-anesthesia, rats treated with anesthesia at 18-months-old demonstrated
      spatial learning impairment corresponding to acute and long-term increases in
      NR2B protein expression and a reduction in phospho-ERK1/2 in the hippocampus and
      cortex. Ro 25-6981 pretreatment attenuated the increase in acute NR2B protein
      expression. Our findings suggest a role for disruption of NMDA receptor mediated
      signaling pathways in the hippocampus and cortex of rats treated with isoflurane/
      N(2)O anesthesia at 18-months-old, leading to spatial learning deficits in these
      animals. A potential therapeutic intervention for anesthesia associated cognitive
      deficits is discussed.

PMID- 22137661
TI  - Phase contrast X-ray synchrotron imaging for assessing external and internal
      morphology of Rhodnius prolixus.
AB  - PhC-SR-MUCT is a nondestructive technique that allows the microanatomical
      investigations and 3D images reconstructions. This technique is performed in
      blood sucker, Rhodnius prolixus--one of the most important insect vectors of
      Trypanosoma cruzi, ethiologic agent of Chagas' disease in Latin America--was able
      to provide excellent information about the microanatomy of the thorax and head
      allowing a new tool for further studies of development and physiology of
      triatomine by a non-invasive method of observation.

PMID- 22137662
TI  - Facile synthesis of carbon-11-labeled arylpiperazinylthioalkyl derivatives as new
      PET radioligands for imaging of 5-HT1AR.
AB  - Carbon-11-labeled arylpiperazinylthioalkyl derivatives, 2-((4-(4-(2
      [(11)C]methoxyphenyl)piperazin-1-yl)butyl)thio)benzo[d]oxazole ([(11)C]5a), 2-((4
      (4-(2-[(11)C]methoxyphenyl)piperazin-1-yl)butyl)thio)-5,7-dimethylbenzo[d]oxazole
      ([(11)C]5c), 2-((4-(4-(2-[(11)C]methoxyphenyl)piperazin-1
      yl)butyl)thio)benzo[d]thiazole ([(11)C]5e), 2-((6-(4-(2
      [(11)C]methoxyphenyl)piperazin-1-yl)hexyl)thio)benzo[d]oxazole ([(11)C]5g), 2-((6
      (4-(2-[(11)C]methoxyphenyl)piperazin-1-yl)hexyl)thio)-5,7-dimethylbenzo[d]oxazole
      ([(11)C]5i), and 2-((6-(4-(2-[(11)C]methoxyphenyl)piperazin-1
      yl)hexyl)thio)benzo[d]thiazole ([(11)C]5k), were prepared from their
      corresponding phenol precursors with [(11)C]CH(3)OTf through O-[(11)C]methylation
      and isolated by a simplified solid-phase extraction (SPE) method using a Sep-Pak
      Plus C18 cartridge in 50-60% (n=5) radiochemical yields based on [(11)C]CO(2) and
      decay corrected to end of bombardment (EOB). The overall synthesis time from EOB
      was 23 min, the radiochemical purity was >99%, and the specific activity at end
      of synthesis (EOS) was 277.5 +/- 92.5 GBq/MUmol (n=5).

PMID- 22137663
TI  - Association between sRAGE, esRAGE levels and vascular inflammation: analysis with
      (18)F-fluorodeoxyglucose positron emission tomography.
AB  - BACKGROUND: The receptor for advanced glycation end-products (RAGE) and its
      diverse ligands play a pivotal role in the development of cardiovascular disease.
      Soluble forms of RAGE (sRAGE), including the splice variant endogenous secretory
      RAGE (esRAGE), may neutralize AGE-RAGE mediated vascular damage by acting as a
      decoy. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a novel
      imaging technique for detecting vascular inflammation. METHODS: We examined
      vascular inflammation measured using FDG-PET in 41 type 2 diabetes patients and
      41 healthy control subjects in the right carotid artery. Vascular (18)F-FDG
      uptake was measured as the blood-normalized standardized uptake value (SUV),
      known as the target-to-background ratio (TBR). In addition, their relationship
      with carotid intima-media thickness (CIMT), estimated GFR (eGFR), and other
      cardiovascular risk factors was evaluated. RESULTS: Both mean and maximum TBR
      values were significantly higher in patients with type 2 diabetes compared to
      healthy subjects. After adjusting for age and gender, sRAGE levels were
      significantly correlated with both mean and maximum TBR values, but not with CIMT
      values. Multiple linear regression analysis showed that maximum TBR values were
      independently associated with sRAGE levels in addition to HbA1c and eGFR.
      CONCLUSIONS: Circulating sRAGE showed significant association with TBR values
      measured using FDG-PET, which reflect vascular inflammation.

PMID- 22137664
TI  - The urokinase system in the pathogenesis of atherosclerosis.
AB  - Atherogenesis refers to the development of atheromatous plaques in the inner
      lining of the arteries. These atherosclerotic lesions are characterized by
      accumulation of monocyte-derived macrophage-foam cells loaded with cholesterol,
      which eventually undergo apoptotic death, leading finally to formation of the
      necrotic core of the plaque. Atheroma formation also involves the recruitment of
      smooth muscle cells (SMC) from the media into the intima, where they proliferate
      and form the neointima in a process called "remodeling". Cells in the advanced
      atherosclerotic plaques express high levels of the serine protease urokinase-type
      plasminogen activator (uPA) and its receptor (uPAR). uPA is a multi-functional
      multi-domain protein that is not only a regulator of fibrinolysis, but it is also
      associated with several acute and chronic pathologic conditions. uPA mediate the
      extracellular matrix (ECM) degradation, and plays a pivotal role in cell
      adhesion, migration and proliferation, during tissue remodeling. On cell surface
      uPA binds to the high affinity urokinase receptor, providing a strictly localized
      proteolysis of ECM proteins. The uPA/uPAR complex also activates intracellular
      signaling, thus regulating cellular function. An imbalance in the uPA/uPAR system
      leads to dis-orders in tissue structure and function. This review summarizes
      recent progress in understanding the role and mechanisms of the uPA/uPAR system
      in atherogenesis.

PMID- 22137665
TI  - The decade of ideas leading to a cure for rickets.

PMID- 22137666
TI  - A randomized, masked study of weekly erythropoietin dosing in preterm infants.
AB  - OBJECTIVE: To compare reticulocyte responses of once-per-week erythropoietin
      (EPO) dosing with 3-times-a-week dosing in preterm infants. STUDY DESIGN: Infants
      weighing <= 1500 g and >= 7 days of age were randomized to once-per-week EPO,
      1200 U/kg/dose, or 3-times-a-week EPO, 400 U/kg/dose, subcutaneously for 4 weeks,
      along with iron and vitamin supplementation. Complete blood counts, absolute
      reticulocyte counts (ARCs), transfusions, phlebotomy losses, and adverse events
      were recorded. RESULTS: Twenty preterm infants (962 +/- 55 g, 27.9 +/- 0.4 weeks,
      17 +/- 3 days of age) were enrolled. Groups were similar at baseline. Infants in
      both groups had increased ARCs, which were similar between treatment groups at
      the start and end of 4 weeks. Hematocrit remained stable, and similar numbers of
      transfusions were administered. No adverse effects of either dosing schedule were
      noted. CONCLUSIONS: Preterm infants respond to weekly EPO by increasing ARCs and
      maintaining hematocrit. We speculate that once-per-week EPO dosing might be
      beneficial to preterm infants requiring increased erythropoiesis.

PMID- 22137668
TI  - The Morton's fork of total parenteral nutrition administration.

PMID- 22137667
TI  - Relationships among obstructive sleep apnea, anthropometric measures, and
      neurocognitive functioning in adolescents with severe obesity.
AB  - OBJECTIVE: To explore associations between measures of obstructive sleep apnea
      (OSA) and sleep quality, anthropometrics, and neurocognitive functioning in
      severely obese adolescents. STUDY DESIGN: This was a cross-sectional pilot study
      performed at an academic medical center in 37 severely obese (body mass index
      [BMI] >97th percentile) adolescents. Study evaluations included polysomnography,
      BMI, waist circumference, and standardized neurocognitive tests to assess memory,
      executive functioning, psychomotor efficiency, academic achievement, and an
      approximation of full-scale IQ. Outcome data were evaluated categorically, based
      on clinical criteria for the diagnosis of OSA, and continuously to quantify
      associations between sleep parameters, anthropometrics, and neurocognitive test
      results. RESULTS: Sleep fragmentation and poorer sleep quality were associated
      with reduced psychomotor efficiency, poorer memory recall, and lower scores on
      standardized academic tests. Having evidence of OSA was associated with lower
      math scores, but not with other neurocognitive measures. BMI and waist
      circumference were negatively associated with oxygen saturation. CONCLUSION: Our
      pilot study findings suggest that sleep fragmentation and poorer sleep quality
      have implications for neurocognitive functioning in obese adolescents. The
      epidemic of childhood obesity has dire implications, not only for increasing
      cardiometabolic pathology, but also for possibly promoting less readily apparent
      neurologic alterations associated with poor sleep quality.

PMID- 22137669
TI  - Hypertension and end-stage renal disease: vital understanding needed.

PMID- 22137670
TI  - Neurally adjusted ventilatory assist in neonates weighing <1500 grams: a
      retrospective analysis.
AB  - OBJECTIVE: To report our experience using neurally adjusted ventilatory assist
      (NAVA), which allows a patient to synchronize spontaneous respiratory effort with
      mechanical ventilation, in the neonatal intensive care unit in neonates weighing
      <1500 g. STUDY DESIGN: This was a retrospective review performed between May 2008
      and May 2009. A total of 52 neonates on conventional ventilation were converted
      to NAVA. We compared ventilatory parameters and blood gas values during
      conventional ventilation and then at various time intervals during NAVA and
      evaluated for complications. Statistical analyses were performed using the 2
      tailed Student t-test and the Z-test for proportions for demographic data and
      Hotelling's T(2) test to compare repeated measures (P < .05). RESULTS: Peak
      inspiratory pressure and fraction of inspired oxygen decreased, and pH and
      partial pressure of carbon dioxide improved during use of NAVA. These changes
      were sustained for 24 hours. CONCLUSION: Compared with standard conventional
      ventilation, in preterm neonates NAVA appears to provide better blood gas
      regulation with lower peak inspiratory pressure and oxygen requirements.

PMID- 22137671
TI  - Hemoglobin A1c above threshold level is associated with decreased beta-cell
      function in overweight Latino youth.
AB  - OBJECTIVE: To examine whether a hemoglobin A1c (HbA1c)-identified prediabetic
      state (HbA1c >= 6.0%-6.4%) is associated with decreased insulin sensitivity (SI)
      and beta-cell dysfunction, known factors in the pathogenesis of type 2 diabetes,
      in an overweight pediatric population. STUDY DESIGN: A total of 206 healthy
      overweight Latino adolescents (124 males and 82 females; mean age, 13.1 +/- 2.0
      years) were divided into 2 groups: lower risk (n=179), with HbA1c <6.0%, and
      higher risk (n=27), with HbA1c 6.0%-6.4%. Measurements included HbA1c, oral
      glucose tolerance testing, fasting and 2-hour glucose and insulin, SI, acute
      insulin response, and disposition index (an index of beta-cell function) by the
      frequently sampled intravenous glucose tolerance test with minimal modeling. Body
      fat was determined by dual-energy X-ray absorptiometry. RESULTS: Compared with
      the lower risk group, the higher risk group had 21% lower SI (1.21 +/- 0.06 vs
      1.54 +/- 0.13; P<.05), 30% lower acute insulin response (928 +/- 102 vs 1342 +/-
      56; P<.01), and a 31% lower disposition index (1390 +/- 146 vs 2023 +/- 83;
      P=.001) after adjusting for age and total percent body fat. CONCLUSION: These
      data provide clear evidence of greater impairment of beta-cell function in
      overweight Latino children with HbA1c 6.0%-6.4%, and thereby support the adoption
      of the International Expert Committee's HbA1c-determined definition of high-risk
      state for overweight children at risk for type 2 diabetes.

PMID- 22137673
TI  - Cellular senescence--a barrier against tumor development?

PMID- 22137674
TI  - Mechanically relevant consequences of the composite laminate-like design of the
      abdominal wall muscles and connective tissues.
AB  - Together, three abdominal wall muscles (external oblique, internal oblique and
      transversus abdominis) form a tightly bound muscular sheet that has been likened
      to a composite-laminate structure. Previous work has demonstrated the ability of
      force generated by these three muscles to be passed between one another through
      connective tissue linkages. Muscle fibres in each muscle are obliquely oriented
      with respect to its neighbouring muscles. It is proposed here is that this unique
      morphology of the abdominal wall muscles functions, through the application of
      constraining forces amongst the muscles, to increase force- and stiffness
      generating capabilities. This paper presents a mathematical formulation of the
      stress-strain relationship for a transversely isotropic fibrous composite, and
      establishes a strengthening and stiffening effect when stress can be transferred
      between the fibrous layers. Application of empirical mechanical properties to
      this formulation demonstrates this effect for the abdominal wall muscles and, in
      greater proportion, for the anterior aponeurosis of the abdominal wall. This has
      implications for increasing the stiffness and passive load bearing ability of the
      abdominal wall muscles, and has the potential to modulate the whole muscle force
      length and force-velocity relationships during contraction.

PMID- 22137672
TI  - Comparison of calcium acetate and sevelamer on vascular function and fibroblast
      growth factor 23 in CKD patients: a randomized clinical trial.
AB  - BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a marker of endothelial
      dysfunction and atherosclerotic complications in patients with chronic kidney
      disease (CKD). Because previous studies suggested that sevelamer may exert
      effects on FGF-23 level and endothelial function independently of its phosphate
      lowering action, we tested the effect of sevelamer versus calcium acetate on
      vascular function and FGF-23 levels. STUDY DESIGN: Randomized prospective open
      label trial. SETTING & PARTICIPANTS: Patients with stage 4 CKD with
      hyperphosphatemia (n = 100). INTERVENTION: An 8-week intervention with sevelamer
      (n = 47) and calcium acetate (n = 53). OUTCOMES: The primary study outcome was
      change in flow-mediated vasodilatation in the forearm. The secondary outcome was
      change in FGF-23 levels. RESULTS: Serum phosphate levels decreased in both
      treatment arms (P < 0.001), but more markedly in the sevelamer group (P < 0.001).
      Flow-mediated vasodilatation increased from 6.1% to 7.1% (P < 0.001) in sevelamer
      treated patients, whereas it was unchanged in the calcium-acetate group (6.0% vs
      6.0%). In a combined analysis, treatment-induced changes in flow-mediated
      vasodilatation were (P < 0.001) associated with simultaneous changes in FGF-23
      levels (-27.1% [-33.2% to -8.8%] for the sevelamer group; 3.5% [-8.4% to 12.1%]
      for the calcium acetate group), as well as with C-reactive protein and fetuin A
      levels. These relationships were confirmed in multiple regression analysis
      adjusting for changes in serum phosphate levels and other factors. LIMITATIONS:
      Unblinded randomized controlled study that cannot establish mechanisms of effect.
      CONCLUSIONS: In hyperphosphatemic patients with stage 4 CKD, treatment with
      phosphate lowering induces measurable improvements in flow-mediated
      vasodilatation. Furthermore, independently of serum phosphate level, FGF-23 level
      changes induced by phosphate binders are associated with simultaneous changes in
      flow-mediated vasodilatation. These observations are compatible with the
      hypothesis that FGF-23 may contribute to vascular dysfunction in this population.

PMID- 22137675
TI  - Automated frequency domain analysis of oxygen saturation as a screening tool for
      SAHS.
AB  - Sleep apnea-hypopnea syndrome (SAHS) is significantly underdiagnosed and new
      screening systems are needed. The analysis of oxygen desaturation has been
      proposed as a screening method. However, when oxygen saturation (SpO(2)) is used
      as a standalone single channel device, algorithms working in time domain achieve
      either a high sensitivity or a high specificity, but not usually both. This
      limitation arises from the dependence of time-domain analysis on absolute SpO(2)
      values and the lack of standardized thresholds defined as pathological. The aim
      of this study is to assess the degree of concordance between SAHS screening using
      offline frequency domain processing of SpO(2) signals and the apnea-hypopnea
      index (AHI), and the diagnostic performance of such a new method. SpO(2) signals
      from 115 subjects were analyzed. Data were divided in a training data set (37)
      and a test set (78). Power spectral density was calculated and related to the
      desaturation index scored by physicians. A frequency desaturation index (FDI) was
      then estimated and its accuracy compared to the classical desaturation index and
      to the apnea-hypopnea index. The findings point to a high diagnostic agreement:
      the best sensitivity and specificity values obtained were 83.33% and 80.44%,
      respectively. Moreover, the proposed method does not rely on absolute SpO(2)
      values and is highly robust to artifacts.

PMID- 22137676
TI  - Comparison of lead aVR "net QRS area" and "peak-to-peak amplitude" as indices of
      all limb electrocardiogram leads: Implications for the diagnosis, management, and
      follow-up in patients with heart failure.
AB  - Nonreproducibility of precordial ECG leads in serial ECGs has led to emphasis on
      the limb leads. The sum of the "peak-to-peak amplitude" (Amp) of the QRS
      complexes of all 6 limb leads ?6LbLds, has been employed as a metric in the
      follow-up of patients with edematous states (ES), including heart failure (HF).
      Since electrocardiographs measure leads I and II and calculate on line the
      remaining 4 limb leads, the sum of leads I and II (I+II), in any mathematical
      form, conceivably may reflect the corresponding variable of ?6LbLds. In turn, due
      to the aVR=-(I+II)/2 relationship, aVR could be regarded as an index of ?6LbLds.
      It is not known whether aVR "net QRS area", i.e., positive minus negative QRS
      areas, has advantages over aVR Amp, as an index of ?6LbLds. Automation-based
      measurements of Amps and "net QRS areas" of all 6 limb leads in 100 consecutive
      ECGs were analyzed, both employing and ignoring the algebraic signs (i.e., using
      the absolute or modulus, or |a| values), in the characterization of lead aVR or
      summations of metrics. There was an excellent correlation between "net QRS area"
      of aVR and I+II, between aVR and ?6LbLds, and between I+II and ?6LbLds (P=0.0005)
      when the algebraic signs were considered. There was an excellent correlation
      between the "net QRS area" of aVR and I+II, and between I+II and ?6LbLds, but the
      correlation between aVR and ?6LbLds (P=0.0005) was good, when the algebraic signs
      were ignored, and lower than when the algebraic signs were considered.
      Correlations between aVR or I+II, with ?6LbLds were better when the Amp(s) than
      the "net QRS area(s) were considered. The QRS Amp aVR is better than the "net QRS
      area" aVR as an index of ?6LbLds; however correlation of all the above ECG
      metrics with body weights and fluid balances in patients with ES and HF are
      needed to identify the optimal ECG metric(s) for clinical adoption.

PMID- 22137677
TI  - Co-localisation of abnormal brain structure and function in specific language
      impairment.
AB  - We assessed the relationship between brain structure and function in 10
      individuals with specific language impairment (SLI), compared to six unaffected
      siblings, and 16 unrelated control participants with typical language. Voxel
      based morphometry indicated that grey matter in the SLI group, relative to
      controls, was increased in the left inferior frontal cortex and decreased in the
      right caudate nucleus and superior temporal cortex bilaterally. The unaffected
      siblings also showed reduced grey matter in the caudate nucleus relative to
      controls. In an auditory covert naming task, the SLI group showed reduced
      activation in the left inferior frontal cortex, right putamen, and in the
      superior temporal cortex bilaterally. Despite spatially coincident structural and
      functional abnormalities in frontal and temporal areas, the relationships between
      structure and function in these regions were different. These findings suggest
      multiple structural and functional abnormalities in SLI that are differently
      associated with receptive and expressive language processing.

PMID- 22137678
TI  - Physicians' attitudes towards self-treatment of latent tuberculosis.
AB  - We conducted a cross-sectional study to assess physicians' attitudes towards self
      treatment of latent tuberculosis infection (LTBI) based on real-time responses
      related to actual purified protein derivative (PPD) results, in addition to using
      hypothetical situations for those who were PPD-negative. We also obtained
      information on physicians' recommendations for their patients to treat this
      condition. Although the physicians claimed to recommend optimal treatment to
      their patients, the majority of them had different attitudes when considering
      treatment for themselves. There appears to be a discrepancy between physicians'
      attitudes to self-treatment and their management of patients with LTBI.

PMID- 22137679
TI  - [Fungal keratitis caused by Cylindrocarpon lichenicola].
AB  - We report a case of a 67-year-old woman with no significant past ocular history,
      who was referred for management of an unresponsive microbial keratitis resulting
      from trauma with a piece of clothing fabric 1 month previously in Portugal and
      worsening despite topical fortified antibiotics. On examination, visual acuity
      was limited to "light perception". Slit lamp examination revealed an 11*11mm full
      thickness corneal infiltrate. Confocal images showed branching hyphae suggestive
      of a fungal infection. Fungal cultures of corneal scrapings revealed growth of
      Cylindrocarpon lichenicola, a saprophytic, filamentous fungus, which is an
      unusual cause of keratitis. Despite aggressive antifungal therapy with
      voriconazole and amphotericin B, she required penetrating keratoplasty for
      impending corneal perforation. Follow-up was uneventful, with no recurrence at 1
      year. Fungal infections must be suspected in all corneal ulcers of traumatic
      etiology. Specific cultures and confocal microscopy must be performed early, so
      as to enable early treatment modification.

PMID- 22137680
TI  - [Superior oblique myokymia: a report of three cases].
AB  - INTRODUCTION: Superior oblique myokymia (SOM/MOS) is an under-recognised and
      probably under-diagnosed disorder. We describe the clinical signs of this
      condition among three patients. Next, from review of the literature, we suggest
      an algorithm for diagnosis and treatment. OBSERVATION: Retrospective study of
      three patients aged 40 to 55 presenting with brief, intermittent monocular
      episodes of oscillopsia. DISCUSSION: The acute symptomatology of superior oblique
      myokymia follows a recognizable pattern: it always presents with brief,
      intermittent monocular vertical oscillopsia and/or vertical diplopia with
      torsion. The clinical signs are related to a neurogenic hyperexcitability of the
      superior oblique muscle. Treatment may be medical (carbamazepine, gabapentin,
      beta-blocker) or surgical. Recent publications report that superior oblique
      myokymia may result from vascular compression of the trochlear nerve (fourth
      cranial nerve), which controls the action of the superior oblique muscle, placing
      this condition in the category of vasculonervous conflicts. CONCLUSION: Superior
      oblique myokymia is a relatively poorly known disorder, despite classic
      pathognomonic symptoms. It is a benign condition, which can nonetheless become
      incapacitating. It occasionally portends an intracranial pathologic process,
      which must then be addressed with specific treatment.

PMID- 22137681
TI  - Nontuberculous mycobacterial infections in cancer patients in a medical center in
      Taiwan, 2005-2008.
AB  - Data on the nontuberculous mycobacterial (NTM) species that cause infection and
      the characteristics of disease caused by these pathogens in cancer patients are
      limited, so we perform this study to investigate the species distribution of NTM
      isolates from various clinical specimens and to elucidate the epidemiologic
      trends in NTM isolates and diseases among cancer patients. From 2005 through
      2008, cancer patients with NTM infections as defined by the American Thoracic
      Society/Infectious Diseases Society of America criteria were identified at the
      National Taiwan University Hospital. The medical records of all patients were
      reviewed. During the study period, a total of 219 cancer patients with NTM
      infections were identified. Among them, 133 (60.7%) patients were older than 65
      years, most of whom were men. Lung cancer was the most common type of cancer,
      followed by hematologic cancer and gastrointestinal tract cancer. Pulmonary NTM
      infection was the most common type of infection in 205 (93.6%) patients, followed
      by skin and soft tissue infections (n = 7, 3.2%), disseminated infections (n = 4,
      1.8%), and genitourinary tract infection (n = 3, 1.4%). Disseminated infections
      occurred exclusively in patients with hematologic cancer. Mycobacterium avium
      complex (MAC) caused the majority of pulmonary NTM infections in cancer patients;
      in contrast, M. abscessus was the most common causative pathogen of
      extrapulmonary NTM diseases, followed by MAC. In conclusion, physicians need to
      be aware of the possibility of co-existing pulmonary NTM infection in patients
      with lung cancer. In addition, disseminated NTM infection should be considered in
      patients with hematologic cancer.

PMID- 22137682
TI  - Validation of a polymerase chain reaction-oligochromatography test for detection
      of influenza A (H1N1) 2009 virus.
AB  - The outbreak of pandemic influenza A (H1N1) 2009 virus caused the first influenza
      pandemic disease of the 21st century. In August 2010, the pandemic moved into the
      post-pandemic period. However, localized outbreaks of various magnitudes
      continued with a higher rate of disease severity. The aim of this study was to
      assess a new polymerase chain reaction (PCR)-oligochromatographic assay (Speed
      Oligo) in the diagnosis of novel influenza A (H1N1) 2009. A total of 405
      nasopharyngeal aspirate specimens from 400 pediatric and adults patients with
      suspected infection of pandemic influenza A (H1N1) 2009 were analyzed. The
      sensitivity and specificity values of the Speed-Oligo assay in comparison to
      reverse transcriptase-PCR assay developed by the Centers for Disease Control and
      Prevention were 86.5% and 92.2%, respectively. The new assay is simple, rapid,
      and provides a good sensitivity for detection of influenza A (H1N1) 2009. This
      assay might be a good alternative to real-time PCR assays for laboratories not
      equipped with real-time PCR instruments.

PMID- 22137683
TI  - Implications of Lactobacillus collinoides and Brettanomyces/Dekkera anomala in
      phenolic off-flavour defects of ciders.
AB  - Different Lactobacillus collinoides and Brettanomyces/Dekkera anomala cider
      strains were studied for their ability to produce volatile phenols in synthetic
      medium. All strains were able to produce 4-ethylcatechol (4-EC), 4-ethylphenol (4
      EP) and 4-ethylguaiacol (4-EG) from caffeic, p-coumaric and ferulic acids,
      respectively. Interestingly, D. anomala and L. collinoides were also able to
      produce 4-EC, 4-EP and 4-EG in cider conditions. The quantities of ethylphenols
      produced by these two species were similar in both tested ciders. The impact of
      precursor quantities was studied and it showed that the addition of caffeic and p
      coumaric acids in ciders allowed for higher 4-EC and 4-EP production by D.
      anomala and L. collinoides. In parallel, D. anomala and L. collinoides strains
      were isolated from a phenolic off-flavour defective bottled cider after
      ethylphenol production hence confirming the implication of these two species in
      this cider spoilage. Finally, detection thresholds of the main ethylphenols were
      determined in ciders by orthonasal and retronasal sampling. The 4-EC and 4-EP
      detection thresholds (close to 20-25mg/l and 1.5-2.0mg/l, respectively) were
      matrix dependant.

PMID- 22137684
TI  - Inactivation of foot-and-mouth disease virus in various bovine tissues used for
      the production of natural sausage casings.
AB  - Bovine intestines, bladders and oesophagus are used for the production of natural
      casings ("beef casings") as edible sausage containers. Derived from cattle
      experimentally infected with FMDV (initial dosage 10(4) TCID(50)/mL, strain A
      Iran 97), these beef casings were treated with sodium chloride (NaCl) or
      phosphate supplemented salt (P-salt). In addition, different in-vitro experiments
      using beef casings were done on a small scale with other FMDV strains (A Turkey
      06, C-Oberbayern and O(1) Manisa) as "proof of principle". Based on the combined
      results of the in-vivo and in-vitro experiments, it can be concluded that the
      storage period of 30 days at 20  degrees C in NaCl is sufficiently effective to
      inactivate a possible contamination with FMDV in beef casings and that the usage
      of P-salt does not clearly enhance the inactivation of FMDV infectivity. Storage
      of salted beef casings at about 20  degrees C for 30 days is already part of the
      Standard Operating Procedures (included in HACCP) of the international casing
      industry and can therefore be considered as a protective measure for the
      international trade in natural casings.

PMID- 22137685
TI  - Extraction of food-borne viruses from food samples: a review.
AB  - Detection of food-borne viruses such as noroviruses, rotaviruses and hepatitis A
      virus in food products differs from detection of most food-borne bacteria, as
      most of these viruses cannot be cultivated in cell culture to date. Therefore,
      detection of food-borne viruses in food products requires multiple steps: first,
      virus extraction; second, purification of the viral genomic material (RNA for the
      majority of food-borne viruses); and last, molecular detection. This review is
      focused on the first step, the virus extraction. All of the numerous published
      protocols for virus extraction from food samples are based on 3 main approaches:
      1) (acid adsorption-) elution-concentration; 2) direct RNA extraction; and 3)
      proteinase K treatment. This review summarizes these virus extraction approaches
      and the results obtained from published protocols. The use of process controls is
      also briefly described.

PMID- 22137686
TI  - Negative pressure wound therapy reduces the ischaemia/reperfusion-associated
      inflammatory response in free muscle flaps.
AB  - BACKGROUND: We recently established negative pressure wound therapy (NPWT) as a
      safe postoperative care concept for free muscle flaps; however, the molecular
      effects of NPWT on free muscle flaps remain elusive. Here we investigated the
      effects of NPWT on pathological changes associated with ischaemia/reperfusion
      injury in free flap tissue. METHODS: From July 2008 to September 2010, 30
      patients receiving skin-grafted free muscle transfer for defect coverage were
      randomly assigned to two treatment groups: In one group the skin-grafted free
      flap was covered by a vacuum dressing (NPWT); in the second group, flaps were
      covered by conventional petroleum gauze dressings (conv). Biopsies were taken
      intra-operatively prior to clipping of the pedicle and on postoperative day 5.
      Samples were analysed by immunohistochemistry for infiltration of inflammatory
      cells, real-time polymerase chain reaction (RT-PCR) for the analysis of
      expression levels of interleukin-1beta (IL-1beta) and tumour necrosis factor
      (TNF)-alpha as markers of inflammation. Histological samples were also examined
      for interstitial oedema formation, and apoptosis was detected by a terminal
      deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. RESULTS: NPWT
      leads to a significantly reduced tissue infiltration of CD68 + macrophages and
      reduced expression of the inflammatory cytokines IL-1beta and TNFalpha. None of
      these parameters was significantly elevated in the pre-ischaemic biopsies.
      Furthermore, NPWT reduced the interstitial oedema formation and the number of
      apoptotic cells in free flap tissue. CONCLUSION: NPWT of skin-grafted free muscle
      flaps leads to a reduced inflammatory response following ischaemia/reperfusion,
      resulting in reduced oedema formation improving the microcirculation and
      ultimately reduced tissue damage. We thereby deliver new insight into the effects
      of NPWT.

PMID- 22137687
TI  - Differentiated and undifferentiated adipose-derived stem cells improve function
      in rats with peripheral nerve gaps.
AB  - The effect of differentiated and undifferentiated adipose-derived stem cells on
      the repair of peripheral nerve gaps was studied. Adipose-derived stem cells were
      maintained in differentiation medium for 2 weeks. The expression of Schwann cell
      proteins S-100, nerve growth factor receptor (NGFR) p75 and integrin beta4 was
      examined by immunofluorescence staining and real time-polymerase chain reaction
      (real time-PCR) at the end of the differentiation period. A 10-mm gap on the left
      sciatic nerves of 20 Fischer rats was created and bridged with silicone tube
      (group I), silicone tube filled with collagen gel (group II), nerve graft (group
      III), silicone tube filled with adipose-derived stem cells (group IV) and
      silicone tube filled with differentiated adipose-derived stem cells (group V). In
      vitro, the positivity of differentiated adipose-derived stem cells for S-100,
      NGFR p75 and integrin beta4 by immunofluorescence staining was 31%, 27% and 12%,
      respectively. Fold changes by real time-PCR in comparison with undifferentiated
      cells were 48.4, 168.7 and 284.85, respectively. In vivo, a walking track
      analysis did not yield any statistically significant differences after 3 months
      postoperatively; however, after 6 months, group IV (sciatic function index (SFI)
      = -49.1 +/- 13.1) and V (SFI = -52.6 +/- 5.7) showed significant improvement
      compared to other groups (I: -73.3 +/- 5.07, II: -79.6 +/- 12.01, III: -74.8 +/-
      12.89) (p < 0.05). Nerve conduction velocity after 6 months was higher in groups
      IV (4.44 +/- 0.3 mm ms(-1)), V (4.25 +/- 0.3 mm ms(-1)) and III (4 +/- 0.3 mm ms(
      1)) than in groups I (2.5 +/- 2.25 mm ms(-1)) and II (2.35 +/- 1.58 mm ms(-1)) (p
      > 0.05). Myelin fibre density and myelinated fibre/unmyelinated fibre ratio were
      significantly higher in the midnerve and the distal nerve in groups IV and V (p <
      0.05). These results reveal the therapeutic potential of adipose-derived stem
      cells in nerve reconstruction.

PMID- 22137688
TI  - Editorial comment.

PMID- 22137690
TI  - Tobacco abuse and the urologist: time for a more proactive role.

PMID- 22137691
TI  - Editorial comment.

PMID- 22137692
TI  - Editorial comment.

PMID- 22137694
TI  - Editorial comment.

PMID- 22137695
TI  - Milk and dairy consumption and risk of bladder cancer: a meta-analysis.
AB  - OBJECTIVE: To explore potential relations between the intake of milk or dairy
      products and the risk of bladder cancer. METHODS: Eligible studies published up
      to May 2011 were retrieved via both computer searches and manual review of
      references. Random-effects models were used to calculate summary relative risk
      estimates (SRRE) based on high-contrast to low-intake values. Sensitivity and
      influence analyses were conducted, and heterogeneity among study results was
      explored through stratified analyses by study design, gender, geographic region,
      year of publication, or whether or not adjustment for several confounders (ie,
      age, gender, body mass index, smoking, and total energy intake). RESULTS: We
      extracted data from 14 studies on milk (involving 4879 cases) and 6 studies on
      dairy products (3087 cases). The total study population was up to 324,241
      individuals. Overall, there was no significant association between milk intake
      and bladder cancer (SRRE 0.89, 95% CI 0.77-1.02). However, an inverse association
      was found in the United States (SRRE 0.88, 95% CI .79-.99). In addition, no
      significant association was observed between consumption of dairy products and
      risk of bladder cancer (SRRE 0.95, 95% CI .71-1.27), though an inverse
      association was detected in the Japanese population (SRRE 0.56, 95% CI .40-.80).
      CONCLUSION: There appears to be enough evidence to support the null hypothesis.
      The overall result was not statistically significant. The findings of this meta
      analysis are not supportive of an independent relationship between the intake of
      milk or dairy products and the risk of bladder cancer. However, these findings
      are based on limited research. Further efforts should be made to confirm these
      findings.

PMID- 22137696
TI  - Cytogenetic and molecular aspects of absolute teratozoospermia: comparison
      between polymorphic and monomorphic forms.
AB  - OBJECTIVE: To compare the results of cytogenetic and molecular analysis between
      absolute polymorphic and monomorphic teratozoospermia. METHODS: The semen samples
      from patients with polymorphic teratozoospermia (n = 20), globozoospermia (n =
      8), or macrocephalic sperm head syndrome (n = 12), and healthy fertile men (n =
      20) were analyzed according to the World Health Organization criteria. The
      constitutional blood karyotype of the patients was performed on cultured
      lymphocytes, according to standard techniques. Microdeletion analysis of the Y
      chromosomes used a sequence tagged site-polymerase chain reaction technique.
      Triple-color fluorescent in situ hybridization for chromosomes X, Y, and 18 were
      used to analyze the meiotic segregation. DNA fragmentation was detected using the
      terminal desoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin
      nick-end labeling assay. RESULTS: Whatever the type of teratozoospermia, a normal
      karyotype and an absence of Y chromosome microdeletion were shown for all
      patients. A significant increase in the sperm aneuploidy rate and DNA
      fragmentation were shown, regardless of the type of teratozoospermia. Spermatozoa
      of the patients with globozoospermia carry an abnormal chromosomal constitution
      and DNA damage rate with the same frequency as that found in the sperm of
      patients with absolute polymorphic teratozoospermia. However, a greater sperm
      aneuploidy rate and DNA fragmentation were found in patients whose
      teratozoospermia was mainly characterized by increased rates of spermatozoa with
      macrocephalic head and multiple flagella. CONCLUSION: Our data have demonstrated
      that DNA fragmentation and sperm aneuploidy are critical tests in
      teratozoospermic men, because the results could negatively affect the
      intracytoplasmic sperm injection outcomes and might play an important role in the
      counseling of couples considering intracytoplasmic sperm injection.

PMID- 22137697
TI  - Empirical treatment of low-level leukocytospermia with doxycycline in male
      infertility patients.
AB  - OBJECTIVE: To design a retrospective study in which infertile men with a seminal
      leukocyte count of 0.2-1 * 10(6) white blood cells [WBC]/mL were given
      doxycycline to examine the potential benefits of the treatment on the improvement
      of semen parameters and natural pregnancy outcomes. It has been reported that
      even low-level leukocytospermia (0.2-1.0 * 10(6) WBC/mL) could be harmful to male
      reproductive function and achievement of pregnancy. METHODS: The records of 223
      patients were reviewed and 61 patients were identified with a leukocyte count of
      0.2-1.0 * 10(6) WBC/mL. Of the 61 patients, 27 presented before 2006 and were not
      routinely treated for this level of leukocytospermia. These patients were our
      historic control population. Since 2006, 34 patients met these criteria and
      received empirical antibiotic therapy (treatment group). RESULTS: The treatment
      of low-level leukocytospermia with doxycycline did not show statistically
      significant differences in the semen parameters among the treated patients.
      Although the therapy did not alter the semen parameters, low-level
      leukocytospermia resolved in 56% of the treatment group, well above the
      spontaneous resolution rate of 25% observed in historic controls. The natural
      pregnancy rate among the treatment group (15 of 32 [47%]) was significantly
      greater than that among the controls (5 of 25 [20%]). The odds ratio for
      pregnancy outcome was 3.7 (95% confidence interval 1.1-11.7; P = .04).
      CONCLUSION: Low-level leukocytospermia might have deleterious effects on male
      fertility, and antibiotic therapy for such a condition might improve the natural
      pregnancy rate among infertile couples.

PMID- 22137698
TI  - Editorial comment.

PMID- 22137699
TI  - Editorial comment.

PMID- 22137700
TI  - Editorial comment.

PMID- 22137702
TI  - Editorial comment.

PMID- 22137705
TI  - Editorial comment.

PMID- 22137704
TI  - Head-to-head comparison of three commonly used preoperative tools for prediction
      of lymph node invasion at radical prostatectomy.
AB  - OBJECTIVE: A formal validation and head-to-head comparison of the National
      Comprehensive Cancer Network (NCCN) practice guideline lymph node invasion (LNI)
      nomogram, Partin tables, and D'Amico risk-classification was conducted for
      prediction of LNI at radical prostatectomy (RP). METHODS: We focused on 20,877
      patients treated with RP and pelvic lymph node dissection (PLND) between 2004 and
      2006 within the Surveillance, Epidemiology and End Results database. The
      discrimination of the 3 tools in predicting histologically confirmed LNI was
      quantified using the area under the curve (AUC). Calibration plots were used to
      graphically depict the performance characteristics of the examined tools. In
      addition, we relied on decision curve analyses to compare the 3 models directly
      in a head-to-head fashion. RESULTS: Overall, 2.5% of patients had LNI. The NCCN
      LNI nomogram (AUC 82%) outperformed the Partin tables (73%) and the D'Amico risk
      classification (75%) for prediction of LNI. Calibration plots revealed that all 3
      tools overestimated the risk of LNI. Partin tables showed the highest net-benefit
      for probability threshold range between 1% and 4%. Conversely, the NCCN LNI
      nomogram showed the highest net-benefit for the remaining threshold
      probabilities. CONCLUSION: The NCCN LNI nomogram had the highest discrimination
      accuracy. However, using the decision curve analysis, the Partin tables
      demonstrated the highest net benefit when a threshold probability of LNI is <4%.
      In contrast, the NCCN LNI nomogram had the highest net benefit when the threshold
      probability used to perform PLND is greater than 4%.

PMID- 22137706
TI  - Editorial comment.

PMID- 22137707
TI  - Editorial comment.

PMID- 22137709
TI  - Editorial comment.

PMID- 22137711
TI  - Editorial comment.

PMID- 22137713
TI  - Editorial comment.

PMID- 22137714
TI  - Temporary targeted hemostasis to facilitate bloodless partial nephrectomy.
AB  - OBJECTIVE: To extend previous robotic-assisted techniques developed in the swine
      model to studies of laparoscopic and open partial nephrectomy conducted in pigs
      and calves, designed to encompass vessel diameters similar to those encountered
      in humans. Lumagel (Pluromed, Woburn, MA), a nontoxic polymer, can be
      administered intra-arterially under fluoroscopic guidance to obtain a bloodless
      operative field during partial nephrectomy while maintaining normal circulation
      to uninvolved renal tissue. METHODS: A total of 10 animals (7 pigs and 3 calves)
      underwent flow interruption to the kidney, 2 with cross-clamping of the main
      renal artery, the remaining with Lumagel. Other than the first pig and calf, all
      the animals then underwent partial nephrectomy. RESULTS: Using Lumagel, targeted
      blood flow interruption was achieved and circulation to the uninvolved renal
      tissue was maintained. Hemostasis lasted for >=30 minutes. The surgical resection
      time averaged 11 minutes (range 10-13) and 23.3 minutes (range 9-40) in the open
      and laparoscopic groups, respectively. The estimated blood loss was negligible,
      with the exception of 2 cases, 1 in which an error in angiographic assessment led
      to an unoccluded vessel near the resection site and a second case in which a
      guidewire was inadvertently passed through a vessel. The interval to complete
      flow return, as determined by direct visualization of the kidney and its
      corresponding angiogram, averaged 7 and 2.5 minutes for Lumagel and arterial
      clamping, respectively. CONCLUSION: Lumagel provides reliable and reproducible
      intraluminal blood flow interruption and flow restoration in both main and
      segmental renal arteries. By providing blood-free resection, the techniques
      described could facilitate partial nephrectomy without global renal ischemia.

PMID- 22137715
TI  - Re: Hemal et al.: Robotic-assisted nephroureterectomy and bladder cuff excision
      without intraoperative repositioning (Urology 2011;78:357-364).

PMID- 22137717
TI  - Re: Lee et al.: Role of genetics in azoospermia (Urology 2011;77:598-601).

PMID- 22137719
TI  - Re: Cheng et al.: shRNA targeting PLC inhibits bladder cancer cell growth in
      vitro and in vivo (Urology 2011;78:474e.7-474e.11).

PMID- 22137720
TI  - Re: Lazarus et al.: Abdominal tuberculosis presenting as an inguinal hernia in a
      child (Urology 2011;77:1470-1471).

PMID- 22137721
TI  - Effect of silencing VDR gene in kidney on renal epithelial calcium transporter
      proteins and urinary calcium excretion in genetic hypercalciuric stone-forming
      rats.
AB  - OBJECTIVE: To address the molecular mechanisms that the vitamin D receptor (VDR)
      in the kidney might contribute to decreased renal calcium reabsorption in
      idiopathic hypercalciuria using genetic hypercalciuric stone-forming (GHS) rats.
      METHODS: We silenced the VDR gene in the GHS and normal control (NC) rat kidney
      in vivo using adenovirus vector-delivered microRNA targeting VDR through renal
      venous transduction. On days 3-21 after injection with adenovirus, the expression
      levels of the VDR, calcium-sensing receptor, and epithelial calcium transporters
      in the kidney were detected. The urine calcium and serum calcium, phosphorus,
      1,25(OH)(2)D(3), and parathyroid hormone levels were measured. RESULTS: The basal
      expression levels in the kidney tissues of VDR, calbindin-D(28k), and calcium
      sensing receptor were significantly greater in the GHS rats than in the NC rats,
      and the basal expression levels of transient receptor potential vanilloid
      receptor subtype 5, transient receptor potential vanilloid receptor subtype 6,
      calbindin-D(9k), and plasma membrane calcium-adenosine triphosphatase were
      significantly lower in the GHS rats than in the NC rats. VDR knockdown in the
      kidney caused significant increase in renal transient receptor potential
      vanilloid receptor subtype 5, sodium/calcium exchanger, and calbindin-D(9k)
      expression levels in the GHS rats. The GHS rats excreted significantly more urine
      calcium after VDR knockdown. The serum calcium, phosphorus, parathyroid hormone,
      and 1,25(OH)(2)D(3) levels were not altered during the study period in the GHS
      and NC rats. CONCLUSION: Our findings suggest that VDR knockdown in the kidney
      can upregulate the expression of transient receptor potential vanilloid receptor
      subtype 5 in GHS rats. However, VDR depletion results in an increase in urine
      calcium excretion. The role of VDR in the hypercalciuric formation needs to be
      elucidated further.

PMID- 22137722
TI  - Dynamic four-dimensional 320 section CT and carpal bone injury - a description of
      a novel technique to diagnose scapholunate instability.

PMID- 22137723
TI  - Adnexal torsion -- a multimodality imaging review.
AB  - Adnexal torsion is a gynaecological surgical emergency as prompt restoration of
      ovarian blood flow may prevent permanent irreversible damage. Patients frequently
      present with non-specific symptoms and signs and therefore adnexal torsion is
      often an unexpected radiological diagnosis. Although ultrasound is the initial
      imaging technique of choice in suspected adnexal torsion, many patients undergo
      computed tomography (CT) or magnetic resonance imaging (MRI) either as a first
      line test following non-specific presentation, or as a confirmatory test
      following equivocal ultrasound findings. Using multiple techniques, this review
      illustrates the wide variety of imaging features observed in adnexal torsion
      enabling a confident diagnosis that may result in a more favourable surgical
      outcome.

PMID- 22137724
TI  - Rosai-Dorfman disease presenting as multiple breast masses in an otherwise
      asymptomatic male patient.

PMID- 22137725
TI  - Introduction: proteinuria in renal transplant patients.

PMID- 22137726
TI  - Proteinuria: detection and role in native renal disease progression.
AB  - The presence of albuminuria or proteinuria constitutes a sign of kidney damage
      and, together with the estimation of glomerular filtration rate, is based on the
      evaluation of chronic kidney disease. Proteinuria is a strong marker for
      progression of chronic kidney disease, and it is also a marker of increased
      cardiovascular morbimortality. Filtration of albumin by the glomerulus is
      followed by tubular reabsorption, and thus, the resulting albuminuria reflects
      the combined contribution of these 2 processes. Dysfunction of both processes may
      result in increased excretion of albumin, and both glomerular injury and tubular
      impairment have been involved in the initial events leading to proteinuria.
      Independently of the underlying causes, chronic proteinuric glomerulopathies have
      in common the sustained or permanent loss of selectivity of the glomerular
      barrier to protein filtration. The integrity of the glomerular filtration barrier
      depends on its 3-layer structure (the endothelium, the glomerular basement
      membrane, and the podocytes). Increased intraglomerular hydraulic pressure or
      damage to glomerular filtration barrier may elicit glomerular or overload
      proteinuria. The mechanisms underlying glomerular disease are very variable and
      include infiltration of inflammatory cells, proliferation of glomerular cells,
      and malfunction of podocyte-associated molecules such as nephrin or podocin.
      Albumin is filtered by the glomeruli and reabsorbed by the proximal tubular cells
      by receptor-mediated endocytosis. Internalization by endocytosis is followed by
      transport into lysosomes for degradation. The multiligand receptors megalin and
      cubilin are responsible for the constitutive uptake in this mechanism. Albumin
      and its ligands induce expression of inflammatory and fibrogenic mediators
      resulting in inflammation and fibrosis resulting in the loss of renal function as
      a result of tubular proteinuria. TGF-beta, which may be induced by albumin
      exposure, may also act in a feedback mechanism increasing albumin filtration and
      at the same time inhibiting megalin- and cubilin-mediated albumin endocytosis,
      leading to increased albuminuria. Urinary proteins themselves may elicit
      proinflammatory and profibrotic effects that directly contribute to chronic
      tubulointerstitial damage. Multiple pathways are involved, including induction of
      tubular chemokine expression, cytokines, monocyte chemotactic proteins, different
      growth factors, and complement activation, which lead to inflammatory cell
      infiltration in the interstitium and sustained fibrogenesis. This
      tubulointerstitial injury is one of the key factors that induce the renal damage
      progression. Therefore, high-grade proteinuria is an independent mediator of
      progressive kidney damage. Glomerular lesions and their effects on the renal
      tubules appear to provide a critical link between proteinuria and
      tubulointerstitial injury, although several other mechanisms have also been
      involved. Injury is transmitted to the interstitium favoring the self-destruction
      of nephrons and finally of the kidney structure.

PMID- 22137727
TI  - Mechanisms and risk factors for the development of the proteinuria after kidney
      transplantation.
AB  - Although the presence of proteinaceous material in the human urine has been
      recognized for the first time more than 3 centuries ago, in spite of the
      sophisticated technologies available today, doubts remain yet about the genesis
      and the exact mechanisms accounting for the presence of proteinuria. The
      knowledge of pathogenic mechanisms of proteinuria is nowadays one of the most
      important themes in the field of nephrology. If we also consider the kidney
      transplant, the matter complicates because of the contribution of some
      immunologic and pharmacologic factors that are not shared with glomerular or
      tubular diseases in native kidneys. The purpose of this review is to update the
      knowledge about the underlying mechanisms for the development of proteinuria
      looking, where possible, at how these occur in kidney transplantation.

PMID- 22137728
TI  - Histology and proteinuria after renal transplantation.
AB  - Proteinuria is a nonspecific sign of the troubled renal allograft. Small
      increases of proteinuria more than 150 mg/d are associated with poor renal
      allograft survival. During the 90s, it was assumed that chronic allograft
      nephropathy, defined as the presence of interstitial fibrosis and tubular
      atrophy, was the histologic lesion responsible for proteinuria and renal function
      deterioration in most kidneys. Thus, the interest to pursue a histologic
      diagnosis in patients with proteinuria or renal function deterioration faded
      during this period. In 2005, the criteria to diagnose chronic humoral rejection,
      a condition that in the previous year was not distinguished from chronic
      allograft nephropathy (CAN), were defined. The description of chronic humoral
      rejection as a major cause of proteinuria and graft loss represented a change of
      paradigm because it became clear that chronic humoral rejection and other
      conditions such as recurrence of original disease, de novo glomerulonephritis,
      polyomavirus infection, and others are responsible for proteinuria. These
      conditions can be diagnosed on histologic and clinical grounds, provided that
      special techniques such as C4d, immunofluorescence, immunohistochemistry,
      electron microscopy, and determination of donor specific antibodies are used.
      Thus, it became rather clear that proteinuria should be studied by means of a
      renal biopsy, especially if we take into consideration that there is very poor
      correlation between the amount of proteinuria and the disease responsible for it.
      Studies based on surveillance biopsies showed that histologic diagnosis precedes
      clinical manifestations. Despite the lack of clinical trials, series of patients
      have shown that different entities respond to different treatments, further
      reinforcing the idea that early diagnosis and early treatment may contribute to
      improve graft outcome.

PMID- 22137729
TI  - mTOR inhibitor-associated proteinuria in kidney transplant recipients.
AB  - The use of mammalian target of rapamycin inhibitor (mTOR-I) after kidney
      transplantation has been associated with a higher incidence of proteinuria
      compared with calcineurin inhibitors (CNIs). This review will focus on mTOR-I
      associated proteinuria in different settings after kidney transplantation: de
      novo mTOR-I treatment in combination with CNI, de novo mTOR-I-containing and CNI
      free treatment, early conversion from a CNI-based regimen to an mTOR-I-based
      regimen, and late conversion. Some possible mechanisms of mTOR-I-induced
      proteinuria will also be reviewed.

PMID- 22137730
TI  - Prognostic significance and diagnosis of proteinuria in renal transplantation.
AB  - Proteinuria is considered one of the most important prognostic markers of chronic
      kidney disease progression in native kidneys. In renal-transplanted population,
      proteinuria presents a high prevalence because early stages and its presence, in
      higher or lower degrees, have been related to the lower graft survival and a
      higher risk of death, mainly because of cardiovascular diseases, in renal
      transplantation. Although there is a good correlation between higher degree
      proteinuria and histologic findings, histology is not very useful in the study of
      lower degree proteinuria. In that case, the knowledge of different types of
      proteins present in urine could be useful to know which type of damage underlies
      on the graft. Proteomics and different laboratory techniques could be helpful to
      identify damage markers on different conditions, especially on tubulointerstitial
      damage, that should have a subtle clinical presentation. Diagnosis of proteinuria
      in renal transplantation follows the same criteria of general population,
      actually, and in the last years, some authors have tried to achieve the
      usefulness of different diagnostic methods such as protein/creatinine ratio or
      albumin/creatinine ratio in the renal-transplanted population in comparison with
      24-hour collected urine diagnostic techniques. Nevertheless, there are no studies
      about the limit to be considered as "normal" in this population, which shows a
      reduced nephron mass and a higher risk of developing proteinuria. Recent
      literature about the prognostic significance of lower degrees of proteinuria on
      graft and patient survival in this population could be the proof that new studies
      are needed to establish the normal threshold of proteinuria to be considered in
      kidney transplantation.

PMID- 22137731
TI  - Management of proteinuria in clinical practice after kidney transplantation.
AB  - Proteinuria is a marker of poor prognosis in kidney transplant recipients as well
      as in nontransplant patients with chronic kidney disease. It negatively
      influences the rate of deterioration of graft renal function, graft survival, and
      more importantly, patient survival. This review analyzes the current knowledge on
      the management of this crucial aspect in kidney transplantation. The reduction of
      proteinuria has demonstrated a beneficial effect on kidney function and also on
      patient survival in nontransplant patients with chronic kidney disease, but
      unfortunately, to date, it has not been possible to demonstrate the same benefit
      in the kidney transplant population (although it probably exists). Nevertheless,
      the appearance of proteinuria in a renal transplant patient must always be
      followed by an investigation on its etiology, and many times, it should include a
      graft biopsy to adequately categorize the underlying process responsible for the
      proteinuria and to establish a correct therapy. Furthermore, in spite of the
      cause of proteinuria, it should be treated to reduce to normal or near-normal
      levels with the objective to eliminate or reduce its negative effects on the
      graft and the cardiovascular system of the patient. The drugs that interfere with
      the renin-angiotensin-aldosterone system, angiotensin-converting enzyme
      inhibitors and angiotensin II receptor blockers, are the cornerstone of the
      management of this complication, and recently, direct renin inhibitors have added
      to the armamentarium. Mono-, dual-, and triple-therapy modalities are discussed,
      as well as other therapies and nonpharmacologic measures.

PMID- 22137732
TI  - New options and perspectives for proteinuria management after kidney
      transplantation.
AB  - Proteinuria has been strongly correlated with reduced function and graft survival
      in kidney-transplanted patients. Data regarding new strategies in proteinuria
      treatment and subsequent allograft survival are lacking. Similarities between
      chronic graft injury and chronic kidney disease (CKD) suggest that the same
      therapeutic antiproteinuric tools should be effective in kidney-transplanted
      patients. The classic strategies to decrease proteinuria such as blood pressure
      control, nicotine cessation, low-salt diet, and maintaining an ideal body weight
      seem to be not enough to achieve proteinuria control. Improvements in our
      understanding of the pathogenesis of CKD have led to the identification of
      several novel targets for proteinuria management. In this review, we discuss
      novel pharmacological approaches that aim to decrease proteinuria in CKD
      patients, including the use of direct renin inhibitors, vitamin D analogs,
      pentoxifylline, and endothelin receptor antagonists. We also discuss the promise
      of using antifibrotic agents to treat proteinuria. The identification of new
      biomarkers of CKD and its progression can help in the selection of the most
      effective treatment for decreasing proteinuria and maintaining kidney function.

PMID- 22137733
TI  - Relative income inequality and selected health outcomes in urban Chinese youth.
AB  - Self reported cross-sectional data gathered in 2002 from 12,449 middle and high
      school students from seven major cities in China were examined to explore the
      association of self-perceived relative income inequality (SPRII) with general
      health status, depression, stress, and cigarette smoking. Two types of self
      perceived relative income were evaluated: household income relative to peers
      (SPRII-S) and relative to their own past (SPRII-P). SPRII-S and SPRII-P were
      coded as three-level categorical variables: lower, equal, and higher. As
      hypothesized, the youth in the "Lower" SPRII-S or SPRII-P groups reported the
      worst general health and the highest levels of depression and stress; the youth
      in the "Higher" groups reported the best general health. Unexpectedly, the youth
      in the "Higher" groups did not report the lowest levels of depression and stress,
      and the relationship between SPRII and cigarette smoking was even less
      straightforward. The expected positive relationship between SPRII and the general
      health status is consistent with previous research, but the relationships between
      SPRII and depression, stress, and cigarette smoking behavior are not. Further
      studies are needed to elucidate the complex associations between SPRII and health
      outcomes in rapidly transforming economies such as China.

PMID- 22137734
TI  - Beyond symptoms: defining primary care mental health clinical assessment
      priorities, content and process.
AB  - The assessment of undifferentiated psychological distress is a daily aspect of
      primary care practice. Primary care practitioners' underlying values influence
      the priorities, process and content of assessment. Currently there is a lack of
      definition of these values in primary care clinical mental health assessment.
      This paper presents the case for adopting the philosophical values and principles
      of holistic transdisciplinary generalism to influence practice worldwide.
      Furthermore, it raises awareness of current constraints on practice, including an
      overreliance on the psychiatric paradigm of care and resulting criteria-based
      diagnoses. Finally, the paper seeks to promote discussion among primary care
      practitioners and researchers globally about how to define primary care clinical
      mental health assessment priorities, process and content.

PMID- 22137735
TI  - Sites for health rights: local, national, regional and global.

PMID- 22137736
TI  - Decreased activity in right-hemisphere structures involved in social cognition in
      siblings discordant for schizophrenia.
AB  - BACKGROUND: Social cognitive deficits contribute to functional disability in
      schizophrenia. Social cognitive tasks in healthy persons consistently evoke
      activation of medial prefrontal cortex, inferior frontal gyrus, temporoparietal
      gyrus, and posterior cingulate cortex/precuneus. We tested the hypothesis that
      patients with schizophrenia and their unaffected siblings share dysfunction of
      the same neural networks. METHODS: Neural activation during emotion processing
      (EP), theory of mind (ToM), and control tasks was measured using functional
      magnetic resonance imaging (fMRI) in 14 patients with schizophrenia, 14
      nonpsychotic siblings of patients with schizophrenia, and 14 matched healthy
      subjects. RESULTS: Compared with healthy controls, patients with schizophrenia
      showed reduced activation of right hemisphere structures involved in EP and ToM
      including inferior frontal gyrus, middle frontal gyrus, and right temporoparietal
      junction. These deficits were shared, in part, by unaffected siblings. The latter
      group demonstrated deficits in bilateral precuneus activation during ToM, not
      present in patients. CONCLUSIONS: Schizophrenia appears to be associated with a
      deficit in activation of right hemisphere components of a ToM network. Such
      deficits are shared in part by those at high genetic risk but unaffected by
      schizophrenia.

PMID- 22137737
TI  - Enzymatic synthesis of an alpha-chitin-like substance via lysozyme-mediated
      transglycosylation.
AB  - The enzymatic synthesis of an alpha-chitin-like substance via a non-biosynthetic
      pathway has been achieved by transglycosylation in an aqueous system of the
      corresponding substrate, tri-N-acetylchitotriose [(GlcNAc)(3)] for lysozyme. A
      significant amount of water-insoluble product precipitated out from the reaction
      system. MALDI-TOFMS analysis showed that the resulting precipitate had a degree
      of polymerization (DP) of up to 15 from (GlcNAc)(3). Solid-state (13)C NMR
      analysis revealed that the resulting water-insoluble product is a chitin-like
      substance consisting of N-acetylglucosamine (GlcNAc) residues joined exclusively
      in a beta-(1->4)-linked chain with stringent regio-/stereoselection. X-ray
      diffraction (XRD) measurement as well as (13)C NMR analysis showed that the
      crystal structure of synthetic product corresponds to alpha-chitin with a high
      degree of crystallinity. We propose that the multiple oligomers form an alpha
      chitin-like substance as a result of self-assembly via oligomer-oligomer
      interaction when they precipitate.

PMID- 22137738
TI  - Structure of the O-specific polysaccharide from a marine bacterium
      Oceanisphaeralitoralis KMM 3654(T) containing ManNAcA.
AB  - The O-specific polysaccharide was isolated from the lipopolysaccharide of a
      marine bacterium Oceanisphaeralitoralis KMM 3654(T) and studied by chemical
      methods along with (1)H and (13)C NMR spectroscopy. The following new structure
      of the O-specific polysaccharide of O. litoralis containing D-glucose and two
      residues of 2-acetamido-2-deoxy-D-mannuronic acid was established: ->4)-alpha-D
      Glcp-(1->4)-beta-D-ManpNAcA-(1->4)-beta-D-ManpNAcA-(1->.

PMID- 22137739
TI  - 2D/3D hybrid structural model of vocal folds.
AB  - The spatial dimensionality of the vocal fold vibration is a common challenge in
      creating parsimonious models of vocal fold vibration. The ideal model is one that
      is accurate, with the lowest possible computational expense. Inclusion of full 3D
      flow and structural vibration typically requires massive amounts of computation,
      whereas reduction of either the flow or the structure to two dimensions
      eliminates certain aspects of physical reality, thus making the resulting models
      less accurate. Previous 2D models of the vocal fold structure have utilized a
      plane strain formulation, which is shown to be an erroneous modeling approach
      since it ignores influential stress components. We herein present a 2D/3D hybrid
      vocal fold model that preserves three-dimensional effects of length and
      longitudinal shear stresses, while taking advantage of a two-dimensional
      computational domain. The resulting model exhibits static and dynamic responses
      comparable to a 3D model, and retains the computational advantage of a two
      dimensional model.

PMID- 22137740
TI  - Old and new heparins.
AB  - Heparin is an effective, relatively safe, inexpensive parenteral antithrombotic
      agent widely used in the prevention and treatment of thromboembolic disorders,
      but it has several limitations such as the marked intra- and inter-patient
      variability in its anticoagulant response, its poor bioavailability at low doses
      and its relatively narrow risk to benefit ratio. Low molecular weight heparins (
      LMWHs), ultra LMWHs and synthetic pentasaccharides have been developed from
      heparin to overcome its limitations. The characteristics of these compounds are
      reviewed along with the description of their approved clinical uses.

PMID- 22137741
TI  - A population-based study of an Italian genetic isolate reveals that mean platelet
      volume is not a risk factor for thrombosis.
AB  - INTRODUCTION: Several studies revealed that mean platelet volume (MPV) was larger
      in the acute phase of arterial and venous thrombosis and predicted a poor
      clinical outcome. It has been suggested that MPV is a risk factor for thrombosis.
      However, it is unclear whether increased platelet size is a cause or a
      consequence of thrombosis. It was the objective of this study to verify whether
      MPV is a risk factor for arterial and venous thrombosis. METHODS: We search for
      associations between platelet parameters and thrombosis by a population-based
      study in 11,084 inhabitants of an Italian genetic isolate characterized by wide
      variability of platelet parameters. To validate this methodology of
      investigation, we also evaluated whether it was able to identify several well
      known thrombotic risk factors in the study population. RESULTS: Statistical
      analysis confirmed that male gender, ageing, hypertension, high total
      cholesterol, low HDL cholesterol, diabetes, obesity and smoking were risk factors
      for arterial thrombosis, while alcohol consumption had a protective effect.
      Female gender, ageing, pregnancy, estroprogestinic treatment, obesity, varicose
      veins were associated with venous thrombosis. At variance, MPV and platelet count
      were unrelated to previous thrombotic events. However, MPV was negatively
      correlated with the time since the last thrombotic event. CONCLUSIONS: This study
      indicated that an epidemiologic study of a population isolate is appropriate for
      the identification of thrombotic risk factors, but it failed to identify such a
      role for MPV. Thus, we suggest that the increased MPV previously described in
      subjects with acute thrombosis was a consequence instead of a cause of
      thrombosis.

PMID- 22137742
TI  - Mechanisms of platelet activation by thrombin: a short history.
AB  - Platelet activation by thrombin is relevant to arterial thrombosis, therefore it
      is an attractive target for the development of new antithrombotic drugs. In the
      1970s the platelet membrane complex glycoprotein (GP) Ib-V-IX was shown to have a
      high affinity binding site for thrombin on GPIbalpha and a substrate cleaved by
      thrombin, GPV. For several years it was considered to be involved in platelet
      activation by thrombin. The discovery of the protease activated receptors (PARs)
      in 1991 was a major breakthrough in the field. The first member of this family of
      receptors to be discovered was PAR1, a seven transmembrane G-protein coupled
      receptor which, upon cleavage by thrombin, unmasks a new amino-terminus able to
      bind intramolecularly to PAR1 itself thus inducing signaling. On human platelets
      PAR1 and, later PAR4, were demonstrated to mediate most of the platelet responses
      to thrombin. However, after the discovery of PARs, different groups demonstrated
      that GPIbalpha is required to stimulate a full platelet activation by thrombin. A
      model where thrombin binds to the GPIb receptor prior to proteolysis of the PAR
      receptors was supported by several lines of evidence. A role for GPV as inhibitor
      of GPIbalpha signaling has been shown by using GPV knock-out mice.
      Crystallographic data suggested that thrombin bound to GPIbalpha might be able to
      interact with other GPIbalpha molecules on the same or other platelets, shedding
      light on a new role for thrombin binding to GPIbalpha. Finally, anti-PAR1
      molecules were developed which are now in phase II and III clinical studies as
      antithrombotic drugs.

PMID- 22137743
TI  - Clinical outcome in Japanese elderly patients with non-valvular atrial
      fibrillation taking warfarin: a single-center observational study.
AB  - BACKGROUND: Although a lower target prothrombin time-international normalized
      ratio (PT-INR) with warfarin therapy is recommended in Japan for atrial
      fibrillation (AF) patients >=70 years of age, few studies have provided
      supporting data. The current study aimed to evaluate the clinical outcome in
      elderly Japanese patients with non-valvular AF who were taking warfarin. METHODS:
      We conducted a cohort study of 845 consecutive non-valvular AF patients >=70
      years of age who were taking warfarin (median age, 74 years; 30.5% women) with a
      median follow-up period of 27 months (4-69 months). Of these patients, 29.7% had
      a history of stoke/transient ischemic attack (TIA), and 73.1% of the patients had
      a CHADS(2) score >=2. The occurrence of thromboembolic events, including ischemic
      stroke, TIA and other systemic embolisms, and major bleeding events were
      validated through a review of medical records. RESULTS: The incidence of
      thromboembolic and major bleeding events were 3.8 and 2.1% per year,
      respectively. A higher incidence of both events was observed in patients with a
      CHADS(2) score >=3. The multivariate analysis showed that prior stroke/TIA (odds
      ratio 1.7, 95% CI 1.0-2.7) and diabetes (odds ratio 1.7, 95% CI 1.0-2.8) were
      independent risks of thromoembolic events. A HAS-BLED score >=3 represented a
      risk for major bleeding (hazard ratio 2.8, 95% CI 1.7-4.6). A PT-INR of 1.5-2.5
      indicated a low incidence of thromboembolic and major bleeding events in patients
      with a CHADS(2) score >=2. CONCLUSIONS: Our results demonstrate that a target PT
      INR of 2.0 and a range of 1.5-2.5 may be safe for elderly Japanese patients with
      non-valvular AF.

PMID- 22137744
TI  - Investigations of Ge-Te-AgI chalcogenide glass for far-infrared application.
AB  - A serious of tellurium based chalcogenide glass were prepared and investigated.
      As it being transparent nearly up to 25 MUm and strong anti-hydrability, it
      becomes an optimized material for far-infrared application. Here, AgI was
      incorporated into the glasses acting as a glass modifier. With the help of AgI, a
      highest glass transition temperature, T(g) (151  degrees C) can be obtained.
      Detailed physics and chemic properties of the glasses were analyzed with DTA and
      XRD. The infrared optical transmission spectra were studied with the help of FTIR
      and Raman test. A purifying process was adopted to eliminate the affections of
      impurities in the tellurium glass. These serious of glasses are all high
      transparent in the 8-20 MUm region, which fits for the applications of far
      infrared optic imaging and sensing.

PMID- 22137745
TI  - An approach for fabricating self-assembled monolayer of gold nanoparticles on
      NH2(+) ion implantation modified indium tin oxide as the SERS-active substrate.
AB  - In this paper, an approach for fabricating an active surface-enhanced Raman
      scattering (SERS) substrate was adopted. This approach was based on the
      assembling of gold nanoparticles (AuNPs) film on NH(2)(+) ion implantation
      modified indium tin oxide (NH(2)/ITO) substrate. Scanning electron microscopy
      (SEM) was used to investigate the surface morphology of the active SERS
      substrate, which showed that large quantities of AuNPs were coated on the
      substrate. Rhodamine 6G (R6G) was used as probe molecules for SERS experiments,
      showing that this new active substrate had sensitivity to SERS response. The
      substrate efficiency was strictly related to the AuNPs morphology, which depended
      on the pH value of the Au colloid used in the assembly process.

PMID- 22137746
TI  - Polymer complexes. LVI. Supramolecular architectures consolidated by hydrogen
      bonding and pi-pi interaction.
AB  - The amidation of aliphatic amine with acryloyl chloride in dry benzene as a
      solvent has been performed. Moreover, the polymer complexes have been prepared
      and structurally characterized by analyses, molar conductance measurements,
      magnetic susceptibility measurements, spectral techniques like IR, UV, NMR, ESR
      and thermal methods. Acryloyl hydrazine (AH) has been shown to behave as a
      bidentate ligand via its nitrogen (NH(2) of hydrazine group) and C-O/C=O
      (acryloyl group) in polymer complexes, all of which exhibit supramolecular
      architectures assembled through weak interaction including hydrogen bonding and
      pi-pi stacking .The magnetic and spectral data indicate a square planar geometry
      for Cu(2+) complexes and an octahedral geometry for Co(II) and UO(2)(II). The ESR
      spectral data of the Cu(II) complexes showed that the metal-ligand bonds have
      considerable covalent character. The thermal stability was investigated using
      thermogravimetric analysis. The results showed that the polymer complexes are
      more stable than the homopolymer.

PMID- 22137747
TI  - Molecular structure, vibrational spectroscopic (FT-IR, FT-Raman), UV-vis spectra,
      first order hyperpolarizability, NBO analysis, HOMO and LUMO analysis,
      thermodynamic properties of benzophenone 2,4-dicarboxylic acid by ab initio HF
      and density functional method.
AB  - The FT-IR (4000-450 cm(-1)) and FT-Raman spectra (3500-100 cm(-1)) of
      benzophenone 2,4-dicarboxylic acid (2,4-BDA) have been recorded in the condensed
      state. Density functional theory calculation with B3LYP/6-31G(d,p) basis set have
      been used to determine ground state molecular geometries (bond lengths and bond
      angles), harmonic vibrational frequencies, infrared intensities, Raman activities
      and bonding features of the title compounds. The assignments of the vibrational
      spectra have been carried out with the help of normal co-ordinate analysis (NCA)
      following the scaled quantum mechanical force field (SQMFF) methodology. The
      first order hyperpolarizability (beta0) and related properties (beta, alpha0 and
      Deltaalpha) of 2,4-BDA is calculated using HF/6-31G(d,p) method on the finite
      field approach. The stability of molecule has been analyzed by using NBO
      analysis. The calculated first hyperpolarizability shows that the molecule is an
      attractive molecule for future applications in non-linear optics. The calculated
      HOMO and LUMO energies show that charge transfer occurs within these molecules.
      Mulliken population analysis on atomic charges is also calculated. Because of
      vibrational analyses, the thermodynamic properties of the title compound at
      different temperatures have been calculated. Finally, the UV-vis spectra and
      electronic absorption properties were explained and illustrated from the frontier
      molecular orbitals.

PMID- 22137748
TI  - Concomitant polymorphism of a pyridine-2,6-dicarboxamide derivative in a single
      space group: experimental and molecular modeling study.
AB  - The title compound, N(2),N(6)-bis{2-[(Z)-2
      hydroxybenzylideneamino]phenyl}pyridine-2,6-dicarboxamide (3), has been
      synthesized by the reaction of 2-{(2-aminophenylimino)methyl}phenol (1) with
      pyridine-2,6-dicarbonyl dichloride (2), and characterized by elemental analysis,
      FT-IR and NMR spectroscopies and thermal analysis. Compounds 1 and 3 were
      evaluated for their antibacterial activities against Gram-positive and Gram
      negative bacteria. The catalytic activity of 3 was also studied, and as a result,
      the in situ prepared three component system Ru(II)/3/KOH is shown to be an
      efficient catalyst for the transfer hydrogenation reaction of various ketones
      under mild conditions. Compound 3 has been crystallized in two polymorphic forms
      under the same conditions, and their crystal structures have been determined
      using single crystal X-ray diffraction technique. The molecular geometry,
      vibrational frequencies and gauge-independent atomic orbital (GIAO) (1)H and
      (13)C NMR chemical shift values of 3 in the ground state have been calculated
      using the density functional theory (DFT/B3LYP) method with the 6-31G(d) basis
      set, and compared with the experimental data. The results are in good agreement
      with experimental data. The effect of different solvents on the geometry,
      vibrational frequencies, total energies and dipole moments was also studied using
      the same method by applying the Onsager Model. There are subtle differences in
      the conformations and packing of the two polymorphs as a consequence of
      intermolecular hydrogen bonding interactions. Therefore, DFT calculations for the
      hydrogen bond interactions in the polymorphs were carried out using same basis
      set. The changes of thermodynamic properties from the monomers to 3 with the
      temperature ranging from 200 K to 400 K have been obtained using the statistical
      thermodynamic method.

PMID- 22137749
TI  - DNA-binding and photocleavage studies of ruthenium(II) complexes containing
      asymmetric intercalative ligand.
AB  - A novel asymmetric ligand 2-(pyridine-2-yl)-1-H-imidazo[4,5-i]dibenzo[2,3-a:2',3'
      c]phenazine (pidbp) and its ruthenium complexes [Ru(L)(2)(pidbp)](2+) (L=bpy (2,
      2'- bipyridine), phen (1, 10 - phenanthroline)), have been synthesized and
      characterized by elemental analysis, ES-MS, (1)H NMR. Various methods support the
      conclusion that both Ru(II) complexes can intercalate into DNA base pairs.
      Complex [Ru(bpy)(2)(pidbp)](2+)4 exhibits its DNA "molecular light switch"
      properties. Furthermore, the two complexes are efficient DNA-photocleavers under
      irradiation at 365 nm, and complex 5 exhibits a stronger DNA-photocleavage
      efficiency than complex 4. The mechanism of DNA cleavage is an oxidative process
      by generating singlet oxygen.

PMID- 22137750
TI  - Bioreactor performance and methanogenic population dynamics in a low-temperature
      (5-18  degrees C) anaerobic fixed-bed reactor.
AB  - The effect of temperature on the functionality of microbial community structure
      in a low temperature, anaerobic fixed-bed reactor was studied by decreasing the
      operating temperature from 18  degrees C to 5  degrees C. The reactor was
      productive within 20 days and produced stable methane content in biogas (above
      77%) throughout the trial period. At 17  degrees C and 15  degrees C, chemical
      oxygen demand (COD) removal efficiency and biogas production of reactor were
      significantly reduced. These might be temperature thresholds when fixed-bed
      reactors are operated under low temperatures. The methanogen community
      composition was analyzed using 16S rRNA gene clone library screening and
      quantitative PCR. At low ambient temperatures, Methanomicrobiales were dominant
      methanogens, and they preferentially adhered to the carbon fiber carrier. The
      results indicated that 16S rRNA levels of Methanomicrobiales and Methanosaetaceae
      in adhering sludge were higher than in deposited sludge, and they all contributed
      to the efficient performance of the fixed-bed reactor at low operating
      temperatures.

PMID- 22137751
TI  - Transcriptome analysis of an oil-rich race A strain of Botryococcus braunii (BOT
      88-2) by de novo assembly of pyrosequencing cDNA reads.
AB  - To gain genetic information of oil-producing algae Botryococcus braunii, a novel
      dataset of 185,936 complementary DNA (cDNA) reads was obtained via pyrosequencing
      for the representative race A strain (strain BOT-88-2) exhibiting high oil
      productivity. The cDNA reads were assembled to retrieve 29,038 non-redundant
      sequences and 964 of them were successfully annotated based on similarity to
      database sequences. The transcriptome data embraced candidate genes for majority
      of enzymes involved in the biosynthesis of unsaturated very long-chain fatty
      acids. The transcriptome dataset has been deposited in the GenBank/EMBL/DDBJ
      database.

PMID- 22137752
TI  - Conceptual design of cost-effective and environmentally-friendly configurations
      for fuel ethanol production from sugarcane by knowledge-based process synthesis.
AB  - In this work, the hierarchical decomposition methodology was used to conceptually
      design the production of fuel ethanol from sugarcane. The decomposition of the
      process into six levels of analysis was carried out. Several options of
      technological configurations were assessed in each level considering economic and
      environmental criteria. The most promising alternatives were chosen rejecting the
      ones with a least favorable performance. Aspen Plus was employed for simulation
      of each one of the technological configurations studied. Aspen Icarus was used
      for economic evaluation of each configuration, and WAR algorithm was utilized for
      calculation of the environmental criterion. The results obtained showed that the
      most suitable synthesized flowsheet involves the continuous cultivation of
      Zymomonas mobilis with cane juice as substrate and including cell recycling and
      the ethanol dehydration by molecular sieves. The proposed strategy demonstrated
      to be a powerful tool for conceptual design of biotechnological processes
      considering both techno-economic and environmental indicators.

PMID- 22137753
TI  - Greenhouse gas reductions through enhanced use of residues in the life cycle of
      Malaysian palm oil derived biodiesel.
AB  - This study identifies the potential greenhouse gas (GHG) reductions, which can be
      achieved by optimizing the use of residues in the life cycle of palm oil derived
      biodiesel. This is done through compilation of data on existing and prospective
      treatment technologies as well as practical experiments on methane potentials
      from empty fruit bunches. Methane capture from the anaerobic digestion of palm
      oil mill effluent was found to result in the highest GHG reductions. Among the
      solid residues, energy extraction from shells was found to constitute the biggest
      GHG savings per ton of residue, whereas energy extraction from empty fruit
      bunches was found to be the most significant in the biodiesel production life
      cycle. All the studied waste treatment technologies performed significantly
      better than the conventional practices and with dedicated efforts of optimized
      use in the palm oil industry, the production of palm oil derived biodiesel can be
      almost carbon neutral.

PMID- 22137754
TI  - Comparisons of glenoid bony defects between normal cadaveric specimens and
      patients with recurrent shoulder dislocation: an anatomic study.
AB  - BACKGROUND: The location and degree of bony defects that can affect clinical
      outcomes remains controversial in recurrent shoulder dislocation. The purpose of
      this study was to define the most common location of glenoid bony defects in
      patients with recurrent shoulder dislocation. MATERIALS AND METHODS: We analyzed
      the shape and aspect ratio of 44 glenoids from deceased donors. Glenoid size was
      analyzed using a 3-dimensional (3D) computed tomography (CT) scan in 24 patients
      with recurrent shoulder dislocation who underwent arthroscopic Bankart repair. We
      measured the distances from the center of the longitudinal axis of the glenoid to
      the anterior glenoid rim at 9 positions, 10 degrees  apart, from 3:00 to 6:00
      o'clock positions in the cadaver and patient groups. We compared the
      quantification of glenoid defects in the 24 patients using the 3D CT scan. A
      predictive model based on a discriminant analysis was developed. RESULTS: The
      largest length differences of the glenoid were at the 3:20 o'clock position. When
      percentage of bone antidefect of the 3:20 o'clock position was used, the model
      predicted the existence of a defect with 89.7% hit ratio. CONCLUSIONS: The major
      direction of the glenoid defect was in a more anterior position rather than the
      anteroinferior glenoid in patients with recurrent shoulder dislocation. The 3:20
      o'clock position was most common location of glenoid defect in shoulder
      instability. This pattern of bone loss should be considered by the surgeon when
      operating on these patients, especially when performing arthroscopic procedures
      for Bankart repair or bone block operations to the glenoid.

PMID- 22137756
TI  - Priority preparedness issues.

PMID- 22137757
TI  - A pivot nurse at triage.
AB  - According to Drs Thom Mayer and Kirk Jensen, widely recognized experts in
      leadership, management, and customer service, "Improving patient flow essentially
      means patients spend exactly the right amount of time at every juncture in their
      journey through an organization, when you improve flow, you can serve more
      patients, with less effort and you can serve them better." 2 Recognizing that
      backups in the emergency department are a result of broken processes throughout
      the hospital is the first step in solving these problems. The most significant
      challenges are the prevailing attitudes that team triage and immediate bedding
      could not be done. Another challenge is the broad reaching nature of the issue.
      ED throughput is truly a system problem. As ED crowding worsens, it is important
      for departments to improve operations to promote patient throughput. No doubt,
      operational bottlenecks at the back end of the emergency department will
      ultimately lead to front-end delays. However, proficient patient processing at
      the ED front end can minimize the time to physician evaluation, increase patient
      satisfaction, and decrease totalED length of stay.

PMID- 22137758
TI  - The clinical nurse leader: improving outcomes and efficacy in the emergency
      department.

PMID- 22137759
TI  - Increased levels of adipokines in bipolar disorder.
AB  - Bipolar disorder (BD) is associated with considerable higher chronic medical
      comorbidities, overweight and obesity. Adipokines are adipocyte-derived secretory
      factors which have functions in immune response and seem to be associated with
      both BD and overweight. The aim of this study was to evaluate the plasma levels
      of adipokines (adiponectin, resistin and leptin) and TNF-alpha and its receptors
      (sTNFR1 and sTNFR2) in BD overweight patients in comparison with overweight
      controls. Thirty euthymic BD type-I patients and thirty controls matched by age,
      gender and body-mass index (BMI) were assessed by Mini-International
      Neuropsychiatric Interview, Young Mania and Hamilton Depression rating scales
      (YMRS and HDRS, respectively). Plasma levels of adiponectin, resistin, leptin,
      TNF-alpha and its soluble receptors were measured by ELISA. BD patients presented
      increased plasma levels of adiponectin (p < 0.001), leptin (p < 0.001) and sTNFR1
      (p = 0.01). Plasma levels of adipokines were not correlated neither with clinical
      parameters nor TNF-alpha, sTNFR1 and sTNFR2 plasma levels. This study provides
      further support to the hypothesis of the immune/inflammatory imbalance in BD.

PMID- 22137760
TI  - Particulate vs. block bone grafts: three-dimensional changes in graft volume
      after reconstruction of the atrophic maxilla, a 2-year radiographic follow-up.
AB  - BACKGROUND: Extensive alveolar bone resorption in the maxilla limits the
      possibility of successful placement and osseointegration of endosseous implants
      for future prosthetic rehabilitation. Autogenous bone from the iliac crest may be
      used as lateral onlays in the atrophic maxilla, both as block and particulate
      bone. To our knowledge, there is no three-dimensional 2-year follow-up study
      measuring the volumetric reduction of the augmented areas comparing particulate
      and block bone grafts. PURPOSE: The aim of this study was to conduct a
      radiographic 2-year follow-up study, using computed tomographic (CT) images in
      order to evaluate and compare the extent of bone graft resorption in the frontal
      maxillae augmented by particulate (test) and block bone (control). MATERIAL AND
      METHODS: Eleven patients treated with iliac bone grafts and oral implants in the
      maxilla were followed with CT examinations directly post grafting and after 2
      years. RESULT: The volumetric changes after 6 months were extensive.
      Additionally, the changes in particulate bone tended to be larger after 2 years
      compared to block bone, using this protocol. However, the difference was not
      statistically significant. CONCLUSION: The present follow-up study showed that
      there is radiographically complete integration and embedding of implants
      installed in grafted bone despite extensive initial graft resorption. There was
      no significant difference in the amount of volumetric reduction between
      particulate bone and block bone grafts.

PMID- 22137761
TI  - Potential for aerosolization of Clostridium difficile after flushing toilets: the
      role of toilet lids in reducing environmental contamination risk.
AB  - BACKGROUND: Toilet facilities in healthcare settings vary widely, but patient
      toilets are commonly shared and do not have lids. When a toilet is flushed
      without the lid closed, aerosol production may lead to surface contamination
      within the toilet environment. AIM: To substantiate the risks of airborne
      dissemination of C. difficile following flushing a toilet, in particular when
      lids are not fitted. METHODS: We performed in-situ testing, using faecal
      suspensions of C. difficile to simulate the bacterial burden found during
      disease, to measure C. difficile aerosolization. We also measured the extent of
      splashing occurring during flushing of two different toilet types commonly used
      in hospitals. FINDINGS: C. difficile was recoverable from air sampled at heights
      up to 25 cm above the toilet seat. The highest numbers of C. difficile were
      recovered from air sampled immediately following flushing, and then declined 8
      fold after 60 min and a further 3-fold after 90 min. Surface contamination with
      C. difficile occurred within 90 min after flushing, demonstrating that relatively
      large droplets are released which then contaminate the immediate environment. The
      mean numbers of droplets emitted upon flushing by the lidless toilets in clinical
      areas were 15-47, depending on design. C. difficile aerosolization and
      surrounding environmental contamination occur when a lidless toilet is flushed.
      CONCLUSION: Lidless conventional toilets increase the risk of C. difficile
      environmental contamination, and we suggest that their use is discouraged,
      particularly in settings where CDI is common.

PMID- 22137762
TI  - Prepatterning of developmental gene expression by modified histones before
      zygotic genome activation.
AB  - A hallmark of anamniote vertebrate development is a window of embryonic
      transcription-independent cell divisions before onset of zygotic genome
      activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking
      of developmental genes by modified histones in sperm suggests a predictive role
      of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles
      provides an opportunity to examine whether genomic enrichment in modified
      histones is present before initiation of transcription. By profiling histone H3
      trimethylation on all zebrafish promoters before and after ZGA, we demonstrate
      here an epigenetic prepatterning of developmental gene expression. This involves
      pre-ZGA marking of transcriptionally inactive genes involved in homeostatic and
      developmental regulation by permissive H3K4me3 with or without repressive H3K9me3
      or H3K27me3. Our data suggest that histone modifications are instructive for the
      developmental gene expression program.

PMID- 22137764
TI  - Intentions and helpfulness beliefs about first aid responses for young people
      with mental disorders: findings from two Australian national surveys of youth.
AB  - BACKGROUND: Youths are important sources of first aid for people close to them
      who are experiencing mental health problems, but their skills are not optimal. A
      better understanding of predictors of young people's first aid intentions and
      beliefs will facilitate future efforts to improve their mental health first aid
      skills. METHODS: Young people's first aid intentions and beliefs were assessed by
      a national telephone survey of 3746 Australian youth aged 12-25 years in 2006. A
      similar survey was repeated in 2011 with 3021 youths aged 15-25 years. In both
      surveys, youths were presented with a vignette portraying depression, psychosis,
      social phobia, or depression with alcohol misuse in a young person. The 2011
      survey also included depression with suicidal thoughts and post-traumatic stress
      disorder. Respondents reported on any past-year experience of mental health
      problems and treatment, exposure to beyondblue and mental health information at
      school or work. RESULTS: The potential value of encouraging professional
      treatment was not universally recognized, although young people were mostly aware
      of and reported the intention to take supportive actions. Respondent age, sex,
      experience of mental health problems, type of mental disorder, and exposure to
      mental health information at school, work, or beyondblue all predicted some
      intentions and beliefs. Some improvements in beliefs were observed between
      surveys. LIMITATIONS: Actual first aid actions and their helpfulness were not
      measured. CONCLUSIONS: Future efforts should target adolescents, males and those
      with recent mental health problems who had not received help. Beyondblue and
      school and work settings may be promising avenues for these efforts.

PMID- 22137763
TI  - Oncogenic RAS regulates BRIP1 expression to induce dissociation of BRCA1 from
      chromatin, inhibit DNA repair, and promote senescence.
AB  - Here, we report a cell-intrinsic mechanism by which oncogenic RAS promotes
      senescence while predisposing cells to senescence bypass by allowing for
      secondary hits. We show that oncogenic RAS inactivates the BRCA1 DNA repair
      complex by dissociating BRCA1 from chromatin. This event precedes senescence
      associated cell cycle exit and coincides with the accumulation of DNA damage.
      Downregulation of BRIP1, a physiological partner of BRCA1 in the DNA repair
      pathway, triggers BRCA1 chromatin dissociation. Conversely, ectopic BRIP1 rescues
      BRCA1 chromatin dissociation and suppresses RAS-induced senescence and the DNA
      damage response. Significantly, cells undergoing senescence do not exhibit a
      BRCA1-dependent DNA repair response when exposed to DNA damage. Overall, our
      study provides a molecular basis by which oncogenic RAS promotes senescence.
      Because DNA damage has the potential to produce additional "hits" that promote
      senescence bypass, our findings may also suggest one way a small minority of
      cells might bypass senescence and contribute to cancer development.

PMID- 22137765
TI  - Usage and reported helpfulness of self-help strategies by adults with sub
      threshold depression.
AB  - BACKGROUND: Informal self-help has the potential to reduce the population burden
      from sub-threshold forms of depression. Evaluating the effectiveness of self-help
      is difficult in controlled trials, but can be assessed with direct ratings by
      consumers. Depression experts have previously rated the likely effectiveness of
      self-help for sub-threshold depression but it is unclear whether the strategies
      are helpful in practice. We report ratings of the effectiveness of self-help as
      used by adults with sub-threshold depression. METHODS: 1326 adults with sub
      threshold depression were recruited over the internet and completed
      questionnaires about their use of 26 self-help strategies for depression
      symptoms. Strategies that had been used were then assessed for their perceived
      helpfulness. RESULTS: Reported strategy helpfulness tended to be consistent with
      expert ratings of likely helpfulness. Exercise or physical activity was rated as
      most helpful while spending time alone was rated as least helpful. There was
      little association at the sample level between how helpful a strategy was rated
      and how frequently it was used. This suggests that the use of self-help is not
      optimal at the population level. Limitations The sample was self-selected and
      frequency of use of self-help was self-rated. CONCLUSIONS: There is room for
      improvement in the use of self-help through increasing the usage of strategies
      that are likely to be helpful and reducing the use of strategies that are
      unhelpful.

PMID- 22137766
TI  - Type 1 diabetes in Cheshire: cardiometabolic risk factor trends (2004-2009).
AB  - AIMS: In the context of changes in the last 10 years in treatment strategies for
      type 1 diabetes we evaluated longitudinal trends in cardiometabolic risk factor
      profiles in a population from North-West England. METHODS: We retrospectively
      examined longitudinal case records for the period for 291 adult patients followed
      up between 2004 and 2009 (age range 16-85). Data search was performed through the
      EMIS(r) software provider using data held in primary care. RESULTS: Longitudinal
      analysis of individually followed patients indicated a mean 0.4% reduction in
      HbA1c from 8.3% (67 mmol/mol) at baseline (p=0.002). The proportion of patients
      with an HbA1c >=10% (86 mmol/mol) at baseline had a significant reduction over
      time from 14.0% to 9.5% (chi(2)=9.4, p=0.002). BMI remained unchanged (28.3 vs
      28.4 kg/m(2)). However total cholesterol fell by 12.5% from 4.8mM to 4.2mM,
      (p<0.0001) with a corresponding 23% reduction in LDL-cholesterol from 3.0mm to
      2.3mM (p<0.0001). There was a significant fall in diastolic BP (78-74 mmHg,
      p=0.0016). In a mixed longitudinal regression model, HbA1c was associated with
      LDL-C (beta=0.28, p<0.001) and age (beta=0.02, p=0.001), independent of BMI,
      gender and systolic BP. DISCUSSION: In spite of intensive work to improve
      glycaemic control in type 1 diabetes, mean HbA1c remains above target for many
      people in our area, highlighting the difficulty of achieving glycaemic targets in
      type 1 diabetes. The significant reduction in diastolic BP, LDL and total
      cholesterol may have long-term benefit in cardiovascular event rate reduction.

PMID- 22137768
TI  - Ground zero beyond Framingham.

PMID- 22137767
TI  - Genomic analyses of aminergic signaling systems (dopamine, octopamine and
      serotonin) in Daphnia pulex.
AB  - Amines are one class of signaling molecules used by nervous systems. In
      crustaceans, four amines are recognized: dopamine, histamine, octopamine, and
      serotonin. While much is known about the physiological actions of amines in
      crustaceans, little is known about them at the molecular level. Recently, we
      mined the Daphnia pulex genome for proteins required for histaminergic signaling.
      Here, we expand this investigation, mining the D. pulex genome for proteins
      necessary for dopamine, octopamine and serotonin signaling. Using known
      Drosophila protein sequences, the D. pulex database was queried for genes
      encoding homologs of amine biosynthetic enzymes, receptors and transporters.
      Among the proteins identified were the biosynthetic enzymes tryptophan
      phenylalanine hydroxylase (dopamine, octopamine and serotonin), tyrosine
      hydroxylase (dopamine), DOPA decarboxylase (dopamine and serotonin), tyrosine
      decarboxylase (octopamine), tyramine beta-hydroxylase (octopamine) and tryptophan
      hydroxylase (serotonin), as well as receptors for each amine and several amine
      transporters (dopamine and serotonin). Comparisons of the Daphnia proteins with
      their Drosophila queries showed high sequence identity/similarity, particularly
      in domains required for function. The data presented in this study provide the
      first molecular descriptions of dopamine, octopamine and serotonin signaling
      systems in Daphnia, and provide foundations for future molecular, biochemical,
      anatomical, and physiological investigations of aminergic signaling in this
      species.

PMID- 22137769
TI  - Moribund sperm in frozen-thawed semen, and sperm motion end points post-thaw and
      post-swim-up, are related to fertility in Holstein AI bulls.
AB  - The objectives were to compare testicular physical characteristics and post-thaw
      sperm characteristics and their associations with fertility in Holstein bulls
      used for AI. Ten Holstein bulls (4-5 y old) were classified as either high
      fertility (HF) or low-fertility (LF; n = 5 each), based on adjusted 56-d non
      return rates [non-return rate (NRR); range (mean +/- SD): 55.6 +/- 4.6 to 71.8 +/
      1.3%). Testicular physical characteristics were not significantly different
      between the two groups. Four ejaculates were collected from each bull and
      cryopreserved. Several indexes of sperm motion (based on computer-assisted sperm
      analysis) at post-thaw and post-swim-up were correlated with NRR. Sperm from HF
      bulls were in transition to a hyperactivated motility pattern, whereas those from
      LF bulls had only a forward progressive motility pattern. In HF vs LF bulls,
      there was a greater percentage of viable sperm after thawing (60.6 +/- 9.7 vs
      49.5 +/- 8.0%, P < 0.05) and after swim-up (70.9 +/- 11.0 vs 63.0 +/- 8.8%, P <
      0.01); these two end points were positively correlated with fertility (r = 0.45,
      P < 0.01 and r = 0.78; P < 0.01, respectively). Furthermore, in HF vs LF bulls,
      the ratio of sperm recovered after swim-up to viable sperm in post-thaw semen was
      higher (P < 0.001), and the proportion of moribund sperm expressed as a
      percentage of live sperm differed (12.6 +/- 3.4 vs. 16.4 +/- 3.1%, P < 0.001) and
      was negatively correlated (r = -0.33, P < 0.05) with fertility. In conclusion,
      fertility of Holstein bulls maintained in a commercial AI center was not
      predicted by testicular physical characteristics, but it was associated with
      differences in moribund sperm in the inseminate, as well as characteristics of
      sperm post-thaw and after swim-up.

PMID- 22137771
TI  - The environmentally sustainable geological repository: the modern role of
      landfilling.

PMID- 22137770
TI  - Contrasting effects of feature-based statistics on the categorisation and basic
      level identification of visual objects.
AB  - Conceptual representations are at the heart of our mental lives, involved in
      every aspect of cognitive functioning. Despite their centrality, a long-standing
      debate persists as to how the meanings of concepts are represented and processed.
      Many accounts agree that the meanings of concrete concepts are represented by
      their individual features, but disagree about the importance of different feature
      based variables: some views stress the importance of the information carried by
      distinctive features in conceptual processing, others the features which are
      shared over many concepts, and still others the extent to which features co
      occur. We suggest that previously disparate theoretical positions and
      experimental findings can be unified by an account which claims that task demands
      determine how concepts are processed in addition to the effects of feature
      distinctiveness and co-occurrence. We tested these predictions in a basic-level
      naming task which relies on distinctive feature information (Experiment 1) and a
      domain decision task which relies on shared feature information (Experiment 2).
      Both used large-scale regression designs with the same visual objects, and mixed
      effects models incorporating participant, session, stimulus-related and feature
      statistic variables to model the performance. We found that concepts with
      relatively more distinctive and more highly correlated distinctive relative to
      shared features facilitated basic-level naming latencies, while concepts with
      relatively more shared and more highly correlated shared relative to distinctive
      features speeded domain decisions. These findings demonstrate that the feature
      statistics of distinctiveness (shared vs. distinctive) and correlational
      strength, as well as the task demands, determine how concept meaning is processed
      in the conceptual system.

PMID- 22137772
TI  - Characterization and control of odorous gases at a landfill site: a case study in
      Hangzhou, China.
AB  - Municipal solid waste (MSW) landfills are one of the major sources of offensive
      odors potentially creating annoyance in adjacent communities. At the end of May
      2007, an odor pollution incident occurred at the Tianziling landfill site,
      Hangzhou, China, where the residents lodged complaints about the intense odor
      from the landfill, which drew a significant attention from the government. In
      this study, ambient air monitoring was conducted at the Tianziling landfill site.
      The main odor composition of the gas samples collected on June 1st 2007 and the
      reduction of various odorous gases from the samples collected on June 1st 2009
      due to the applied odor control techniques were determined using gas
      chromatography-mass spectrometry (GC-MS). In addition, variations of primary
      odorous gaseous (NH(3) and H(2)S) concentrations at different locations in the
      landfill site from July 2007 to June 2009 were also investigated by using
      classical spectrophotometric methods. Results showed that a total of 68 volatile
      compounds were identified among which H(2)S (56.58-579.84 MUg/m(3)) and NH(3)
      (520-4460 MUg/m(3)) were the notable odor components contributing to 4.47-10.92%
      and 83.91-93.94% of total concentrations, respectively. Similar spatial and
      temporal shifts of H(2)S and NH(3) concentrations were observed and were
      significantly affected by environmental factors including temperature, air
      pressure and wind direction. Odor pollution was worse when high temperature, high
      humidity, low air pressure, and southeast, northeast or east wind appeared.
      Moreover, the environmental sampling points of the dumping area and the leachate
      treatment plant were found to be the main odor sources at the Tianziling landfill
      site. The odor control technologies used in this project had a good mitigating
      effect on the primary odorous compounds. This study provides long-term valuable
      information concerning the characteristics and control of odors at landfill sites
      in a long run.

PMID- 22137773
TI  - Experimental infection of rabbits (Oryctolagus cuniculus) with Brucella suis
      biovar 1 isolated from wild hares (Lepus europaeus).
AB  - Brucella suis biovar 1 is the causative agent of brucellosis in several domestic
      and wild animals and it is a common agent of human brucellosis. European hares
      (Lepus europaeus) have been shown to be infected by B. suis biovar 1 and the
      transmission to other animals has been suggested. In this work, experimental
      rabbits (Cuniculus orictolagus) were infected with B. suis biovar 1 isolated from
      wild hares. Infected rabbits showed high serological response in 2 weeks after
      discharge and typical granulomatous lesions (2mm diameter) were found in liver,
      spleen and kidneys after 50 days. B. suis biovar 1 was cultured from the lesion
      of the organs mentioned above as well as from urine, placenta and fetuses. These
      data suggest that hares are a potential source for horizontal transmission of B.
      suis biovar 1 to other mammalians.

PMID- 22137774
TI  - European guidance: a project of the European Psychiatric Association.
AB  - Evidence based medicine is a cornerstone of modern medicine including psychiatry.
      Treatment practice guidelines are nowadays available for guiding mental health
      care mainly with a focus on specific disorders. Many important clinical
      situations or problems beyond treatment, however, are lacking proper guidance. It
      is in this scope that a European Psychiatry Association (EPA) has developed its
      own program, the European Guidance Project. The present special issue presents
      six topics out of these series of guidance documents.

PMID- 22137775
TI  - The European Psychiatric Association (EPA) guidance on suicide treatment and
      prevention.
AB  - Suicide is a major public health problem in the WHO European Region accounting
      for over 150,000 deaths per year. SUICIDAL CRISIS: Acute intervention should
      start immediately in order to keep the patient alive. DIAGNOSIS: An underlying
      psychiatric disorder is present in up to 90% of people who completed suicide.
      Comorbidity with depression, anxiety, substance abuse and personality disorders
      is high. In order to achieve successful prevention of suicidality, adequate
      diagnostic procedures and appropriate treatment for the underlying disorder are
      essential. TREATMENT: Existing evidence supports the efficacy of pharmacological
      treatment and cognitive behavioural therapy (CBT) in preventing suicidal
      behaviour. Some other psychological treatments are promising, but the supporting
      evidence is currently insufficient. Studies show that antidepressant treatment
      decreases the risk for suicidality among depressed patients. However, the risk of
      suicidal behaviour in depressed patients treated with antidepressants exists
      during the first 10-14 days of treatment, which requires careful monitoring.
      Short-term supplementary medication with anxiolytics and hypnotics in the case of
      anxiety and insomnia is recommended. Treatment with antidepressants of children
      and adolescents should only be given under supervision of a specialist. Long-term
      treatment with lithium has been shown to be effective in preventing both suicide
      and attempted suicide in patients with unipolar and bipolar depression. Treatment
      with clozapine is effective in reducing suicidal behaviour in patients with
      schizophrenia. Other atypical antipsychotics are promising but more evidence is
      required. TREATMENT TEAM: Multidisciplinary treatment teams including
      psychiatrist and other professionals such as psychologist, social worker, and
      occupational therapist are always preferable, as integration of pharmacological,
      psychological and social rehabilitation is recommended especially for patients
      with chronic suicidality. FAMILY: The suicidal person independently of age should
      always be motivated to involve family in the treatment. SOCIAL SUPPORT:
      Psychosocial treatment and support is recommended, as the majority of suicidal
      patients have problems with relationships, work, school and lack functioning
      social networks. SAFETY: A secure home, public and hospital environment, without
      access to suicidal means is a necessary strategy in suicide prevention. Each
      treatment option, prescription of medication and discharge of the patient from
      hospital should be carefully evaluated against the involved risks. TRAINING OF
      PERSONNEL: Training of general practitioners (GPs) is effective in the prevention
      of suicide. It improves treatment of depression and anxiety, quality of the
      provided care and attitudes towards suicide. Continuous training including
      discussions about ethical and legal issues is necessary for psychiatrists and
      other mental health professionals.

PMID- 22137776
TI  - Systematic review and meta-analysis of vagus nerve stimulation in the treatment
      of depression: variable results based on study designs.
AB  - PURPOSE: To determine the efficacy of vagus nerve stimulation (VNS) for treatment
      of depression. METHODS: We conducted a systematic review and meta-analysis of
      analytical studies. Efficacy was evaluated according to severity of illness and
      percentage of responders. RESULTS: We identified 687 references. Of these, 14 met
      the selection criteria and were included in the review. The meta-analysis of
      efficacy for uncontrolled studies showed a significant reduction in scores at the
      Hamilton Depression Rating Scale endpoint, and the percentage of responders was
      31.8% ([23.2% to 41.8%], P<0.001). However, the randomised control trial which
      covered a sample of 235 patients with depression, reported no statistically
      significant differences between the active intervention and placebo groups
      (OR=1.61 [95%CI 0.72 to 3.62]; P=0.25). To study the cause of this heterogeneity,
      a meta-regression was performed. The adjusted coefficient of determination
      (R2(Adj)) was 0.84, which implies that an 84% variation in effect size across the
      studies was explained by baseline severity of depression (P<0.0001). CONCLUSION:
      Currently, insufficient data are available to describe VNS as effective in the
      treatment of depression. In addition, it cannot be ruled out that the positive
      results observed in the uncontrolled studies might have been mainly due to a
      placebo effect.

PMID- 22137777
TI  - Elevated expression of PEG10 in human placentas from preeclamptic pregnancies.
AB  - The aim of this study was to determine qualitative and quantitative changes in
      paternally expressed gene 10 (PEG10) expression in preeclamptic placentas.
      Placental tissues were obtained immediately after delivery from women with normal
      pregnancies (n=20) and patients with preeclampsia (n=20). Quantitative real-time
      RT-PCR, Western blot analysis and immunohistochemistry were used to determine
      PEG10 gene expression and localization in placental tissues. Compared with the
      normal group, PEG10 was highly expressed at both mRNA and protein levels in
      preeclampsia (P<0.05). In immunohistochemical staining, PEG10 was present in the
      syncytiotrophoblast, cytotrophoblast, endothelial cell and stroma of all
      placentas. Notably, the intensity of PEG10 expression in the syncytiotrophoblast,
      cytotrophoblast and stem villi was much higher in preeclampsia than in normal. In
      conclusion, elevated expression of PEG10 is likely to be involved in the
      pathophysiology of preeclampsia. Further studies are needed to elucidate the
      precise role of PEG10 in preeclampsia.

PMID- 22137779
TI  - Stereochemical characterization of fluorinated 2-(phenanthren-1-yl)propionic
      acids by enantioselective high performance liquid chromatography analysis and
      electronic circular dichroism detection.
AB  - Enantioselective high performance liquid chromatography (HPLC) coupled with a
      detection system based on the simultaneous measurement of UV absorption and
      electronic circular dichroism (ECD) allows a complete stereochemical
      characterization of chiral compounds, once the relationship between sign of the
      chiroptical properties and absolute configuration is determined. In the present
      communication, the development of enantioselective HPLC methods for the
      resolution of a series of fluorinated 2-phenanthrenylpropionic acids (1-6) is
      reported. Different chiral stationary phases (CSPs) were tested: Chiralcel OJ,
      Chiralcel OD, Chiralpak AD, (S,S)-Whelk-O 1, Chirobiotic T and alpha(1)-acid
      glycoprotein (AGP). The results allow the application of the methods to a
      reliable determination of the enantiomeric excess for all the examined compounds;
      the highest enantioselectivity values were obtained with the Hibar [(S,S)-Whelk-O
      1] column for some of the examined compounds. In the case of rac-2-(6
      fluorophenanthren-1-yl)propionic acid (1), the relationship between circular
      dichroism and absolute configuration of the enantiomeric fractions was determined
      by ECD analysis and time-dependent density functional theory (TD-DFT)
      calculations. The experimental ECD spectrum of the second-eluted fraction of 1 on
      the Hibar [(S,S)-Whelk-O 1] column was found to be in excellent agreement with
      the theoretical ECD spectrum of (S)-1; therefore, the absolute configuration of
      the first- and second-eluted enantiomers on the (S,S)-Whelk-O 1 CSP was assessed
      as (R) and (S), respectively, and the elution orders of the enantiomeric forms of
      1 were determined on all the different CSPs.

PMID- 22137778
TI  - Determination of sevoflurane and its metabolite hexafluoroisopropanol by direct
      injection of human plasma into gas chromatography-tandem mass spectrometry.
AB  - The developed method for trace analysis of volatile components in plasma allows
      direct injection of up to 150 samples to the GC-MS/MS system without injector
      cleaning. This method requires no modification of plasma and the working
      environment does not interfere with the determination of these analytes. The
      method allows simultaneous quantification of non-polar sevoflurane and its polar
      metabolite hexafluoroisopropanol (free, unconjugated form). It is characterized
      by high repeatability and sensitivity with the detection limit of 0.009 mg L(-1)
      for sevoflurane and 0.018 mg L(-1) for hexafluoroisopropanol and the linear range
      0.050-150 mg L(-1). The method was used to determine the concentration of
      sevoflurane and hexafluoroisopropanol in plasma samples of 7 patients undergoing
      general anesthesia with sevoflurane. The average concentration of sevoflurane and
      free hexafluoroisopropanol was 57.2 mg L(-1) and 0.39 mg L(-1), respectively. The
      method can be applied for clinical monitoring, as well as for analytical
      toxicology.

PMID- 22137780
TI  - Effect of methanol quality on the ionisation of herbicides, insecticides and
      fungicides using gradient elution liquid chromatography.
AB  - This paper explores the changes in the electrospray signal response of 39
      structurally different compounds caused by the quality of the methanol, when used
      as a component in a gradient elution mobile phase. When three batches of LC-MS
      grade methanol from one manufacturer were evaluated, the largest variation in the
      electrospray signal responses of the 39 compounds examined was 18%. However,
      significant enhancement of the electrospray signals of up to 106% were observed
      among different brands of LC-MS grade methanol from different manufacturers. The
      effect of methanol quality on signal response was found to be compound dependent.
      This study also demonstrated that the senescence of the methanol was important.
      Using an expired batch of LC-MS grade methanol, electrospray signals were
      suppressed by as much as 95% for all compounds measured using positive mode
      electrospray. Conversely, the negative mode electrospray signals of compounds
      such as 4-octyl benzoic acid showed an enhancement of up to 96% when using the
      same batch of methanol. Linuron was used as a model compound to examine the
      change in the electrospray response, during gradient elution, when the proportion
      of an expired batch of methanol was varied. An infusion experiment showed that
      the linuron signal intensity decreased as the proportion of expired methanol
      increased in the mobile phase, which was in direct contrast to the increase in
      linuron signal observed with a non-expired batch of methanol. A series of
      isocratic experiments also showed that the linuron signal decreased as the
      proportion of expired methanol increased in the mobile phase. The ion ratios of
      several of the compounds studied changed significantly when using the expired
      batch of LC-MS methanol. The change in the ion ratios accentuates the difficulty
      of identifying compounds from in-source spectral libraries. A protocol is
      recommended for assessing the quality of methanol for LC-MS applications.

PMID- 22137781
TI  - Development of extraction methods for the analysis of perfluorinated compounds in
      human hair and nail by high performance liquid chromatography tandem mass
      spectrometry.
AB  - Perfluorinated compounds (PFCs) are ubiquitous in the environment and are
      becoming a public health concern. It is desirable to develop sensitive and
      accurate methods to measure PFCs in non-invasive matrices such as hair and nail
      for biomonitoring of body burden. Different extraction methods coupled with solid
      phase extraction were investigated for extraction efficiency. The extracts were
      separated, identified and quantified by liquid chromatography-tandem mass
      spectrometry. Extraction with acetonitrile proved to be the most efficient
      extraction method for human hair sample, while extraction by methanol with
      alkaline digestion performed best for human nail sample. The matrix recoveries of
      the optimized methods ranged from 78% to 116% for hair and from 87% to 126% for
      nail sample. The ranges of the limit of detection (LOD) were 0.026-0.069 ng/g and
      0.023-0.094 ng/g for hair and nail, respectively. These methods were validated by
      evaluating LOD, accuracy and precision and were proven to be useful for measuring
      paired human hair and nail samples collected from the general population.

PMID- 22137782
TI  - Needle trap micro-extraction for VOC analysis: effects of packing materials and
      desorption parameters.
AB  - Combining advantages of SPE and SPME needle trap devices (NTD) represent
      promising new tools for a robust and reproducible sample preparation. This study
      was intended to investigate the effect of different packing materials on efficacy
      and reproducibility of VOC analysis by means of needle trap micro extraction
      (NTME). NTDs with a side hole design and containing different combinations of
      PDMS, DVB and Carbopack X and Carboxen 1000 and NTDs containing a single layer
      organic polymer of methacrylic acid and ethylene glycol dimethacrylate were
      investigated with respect to reproducibility, LODs and LOQs, carry over and
      storage. NTDs were loaded with VOC standard gas mixtures containing saturated and
      unsaturated hydrocarbons, oxygenated and aromatic compounds. Volatile substances
      were thermally desorbed from the NTDs using fast expansive flow technique and
      separated, identified and quantified by means of GC-MS. Optimal desorption
      temperatures between 200 and 290 degrees C could be identified for the different
      types of NTDs with respect to desorption efficiency and variation. Carry over was
      below 6% for polymer packed needles and up to 67% in PDMS/Carboxen 1000 NTDs.
      Intra and inter needle variation was best for polymer NTDs and consistently below
      9% for this type of NTD. LODs and LOQs were in the range of some ng/L.
      Sensitivity of the method could be improved by increasing sample volume. NTDs
      packed with a copolymer of methacrylic acid and ethylene glycol dimethacrylate
      were universally applicable for sample preparation in VOC analysis. If aromatic
      compounds were to be determined DVB/Carboxen 1000 and DVB/Carbopack X/Carboxen
      1000 devices could be considered as an alternative. PDMS/Carbopack X/Carboxen
      1000 NTDs may represent a good alternative for the analysis of hydrocarbons and
      aldehydes. NTME represents a powerful tool for different application areas, from
      environmental monitoring to breath analysis.

PMID- 22137783
TI  - Anhedonia in Japanese patients with Parkinson's disease: analysis using the
      Snaith-Hamilton Pleasure Scale.
AB  - BACKGROUND: Anhedonia, a lowered ability to experience physical or social
      pleasure, has recently been recognized as a non-motor symptom of Parkinson's
      disease. OBJECTIVE: To identify the frequency of anhedonia and the factors
      influencing hedonic tone in Japanese patients with Parkinson's disease. PATIENTS
      AND METHODS: We recruited 86 consecutive outpatients with a clinical diagnosis of
      PD attending two Japanese hospitals (one university hospital and one community
      hospital) in February 2010. We used the self-rating Snaith-Hamilton Pleasure
      Scale (SHAPS) translated into Japanese language from the original English version
      to assess and quantify hedonic tone as a subjectively experienced phenomenon. We
      studied the association of anhedonia with the variables age, age at onset,
      gender, disease duration, disease severity and antiparkinsonian drugs. RESULTS:
      Thirty-nine patients (45%) were male and 47 (55%) were female. Mean age was
      72.01+/-9.07 (49-89) years, with mean age at onset of 64.93+/-11.42 (31-88)
      years. Mean disease duration was 7.20+/-5.54 (1-23) years. The mean Hoehn and
      Yahr scale was 2.76+/-0.78. The mean SHAPS score of the total sample was 1.19+/
      1.86. The SHAPS score of 14 patients (16.3%) was 3 or more, indicating anhedonia.
      The mean SHAPS score was lower in patients taking pramipexole (0.58+/-0.97) than
      in patients not taking pramipexole (1.57+/-2.16). Multiple linear regression
      analysis identified pramipexole as a significant negative influencing factor on
      the SHAPS score, while disease severity and entacapone treatment were identified
      as positive influencing factors. The age, onset age, gender, disease duration,
      and use of pergolide, amantadine, zonisamide, selegiline, anticholinergic agents
      and droxidopa did not significantly affect the SHAPS score. CONCLUSION: Anhedonia
      is not rare non-motor symptom in Japanese patients with Parkinson's disease. This
      study suggests an anti-anhedonic property of pramipexole.

PMID- 22137784
TI  - Prediction of infarct growth and neurologic deterioration in patients with
      positive perfusion-diffusion mismatch.
AB  - BACKGROUND: To assess the value of baseline clinical severity and perfusion
      diffusion mismatch as predictors for further infarct growth and clinical outcome.
      METHODS: Patients with acute ischemic stroke and initial perfusion-diffusion
      mismatch within 72 h were enrolled. Baseline perfusion defects on time-to-peak
      (TTP) and cerebral blood volume (CBV) maps were measured. Infarct volume and
      stroke severity were assessed by diffusion-weighted image (DWI) and NIHSS, and
      were repeatedly assessed 7 days later. The predictive value of baseline NIHSS and
      perfusion defects on further infarct growth and neurologic deterioration was
      determined. RESULTS: Fifty-two patients (mean age 68.3+/-12.8 years, 42% women)
      were enrolled. CBV defects were significantly associated with infarct growth
      (CBV, p=0.02). Initial stroke severity, but not TTP and CBV mismatch (p=0.65 and
      0.76, respectively), significantly inversely correlated with neurologic
      deterioration (p=0.001). CONCLUSIONS: In patients with mismatch, those with
      severe symptoms initially are more likely to have infarct growth, while those
      with minor symptoms tend to suffer from larger extent of neurologic deterioration
      within 1 week. CBV is associated with further infarct growth but not clinical
      deterioration.

PMID- 22137785
TI  - Inhibitors of human 2,3-oxidosqualene cyclase (OSC) discovered by virtual
      screening.
AB  - Five human 2,3-oxidosqualnene cyclase (OSC) inhibitors were discovered using the
      combination of a virtual screening based on a docking study and an isotope-free
      assay system. All of these inhibitors were revealed to have activities comparable
      or superior to that of LDAO, a known OSC inhibitor. The computational study of
      the newly identified inhibitors suggested that CH/pi interactions with F444 and
      W581 contribute to the binding, and these interactions are candidates for
      additional structural filters in the next generation of virtual screening.

PMID- 22137786
TI  - Hydroxycoumarins as selective MAO-B inhibitors.
AB  - A series of 3-aryl-4-hydroxycoumarin derivatives was synthesized with the aim to
      find out the structural features for the MAO inhibitory activity and selectivity.
      Methoxy and/or chloro substituents were introduced in the 3-phenyl ring, whereas
      the position 6 in the coumarin moiety was not substituted or substituted with a
      methyl group or a chloro atom due to their different electronic, steric and/or
      lipophilic properties. Most of the synthesized compounds presented MAO-B
      inhibitory activity. The presence of methoxy and chloro groups, respectively in
      the para and meta positions of the 3-phenyl ring, have an important influence on
      the inhibitory activity. Moreover, the presence of a chloro atom in the six
      position of the moiety (compound 7) improved the inhibitor activity as well as
      its selectivity against MAO-B compared with iproniazide, used as reference
      compound. Docking experiments were carried out to understand which are the most
      energetically preferred orientations adopted by compounds 5, 6 and 7 inside the
      MAO-B binding pocket.

PMID- 22137787
TI  - Synthesis and SAR study of imidazoquinolines as a novel structural class of
      microsomal prostaglandin E2 synthase-1 inhibitors.
AB  - The imidazoquinoline derivative 1 was found as a novel mPGES-1 inhibitor.
      Optimization of 1 led to the identification of the 2-chlorophenyl group at the
      C(2)-position and the quinolone structure at the C(4)-position. Compound 33, the
      most potent synthesized compound, showed excellent mPGES-1 inhibition
      (IC(50)=9.1nM) with high selectivity (>1000-fold) over both COX-1 and COX-2.

PMID- 22137788
TI  - Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of
      PRL-3 phosphatase activity.
AB  - Anthraquinones have been reported as phosphatase inhibitors. Therefore,
      anthraquinone derivatives were screened to identify a potent phosphatase
      inhibitor against the phosphatase of regenerating liver-3 (PRL-3). Emodin
      strongly inhibited phosphatase activity of PRL-3 with IC(50) values of 3.5MUM and
      blocked PRL-3-induced tumor cell migration and invasion in a dose-dependent
      manner. Emodin rescued the phosphorylation of ezrin, which is a known PRL-3
      substrate. The results of this study reveal that emodin is a PRL-3 inhibitor and
      a good lead molecule for obtaining a selective PRL-3 inhibitor.

PMID- 22137789
TI  - Towards a modern definition of vitamin E-evidence for a quinone hypothesis.
AB  - We report on the synthesis, biological and pharmacological activity of the
      tocoquinone natural product, alpha-tocopherol quinone (ATQ); an oxidative
      metabolite of alpha-tocopherol. ATQ is a potent cellular protectant against
      oxidative stress, whose biological activity is dependent upon its ability to
      undergo reversible two-electron redox cycling. ATQ is orally bioavailable, with a
      favorable pharmacokinetic profile and has demonstrated a beneficial clinical
      response in patients with Friedreich's ataxia. ATQ is a member of a broader class
      of vitamin E derived quinone metabolites which may be ascribable in whole or in
      part to the activity of vitamin E.

PMID- 22137790
TI  - 4-arylphthalazin-1(2H)-one derivatives as potent antagonists of the melanin
      concentrating hormone receptor 1 (MCH-R1).
AB  - A novel series of 4-arylphthalazin-1(2H)-one linked to arylpiperidines were
      synthesized and evaluated as MCH-R1 antagonists. The results of an extensive SAR
      study probing the effects of substituents on the 4-arylphthalazin-1(2H)-one C-4
      aryl group led to the identification of the 4-(3,4-difluorophenyl) derivative as
      a highly potent MCH-R1 inhibitor with an IC(50)=1nM. However, further
      investigations showed that this substance has unacceptable pharmacokinetic
      properties including a high clearance and volume of distribution.

PMID- 22137791
TI  - Effect of storage method and extender osmolality in the quality of cryopreserved
      epididymal ram spermatozoa.
AB  - Post-mortem sperm recovery and cryopreservation could be a complement to
      germplasm banking in sheep, especially for endangered breeds. This study is an
      attempt to identify factors for improving the success of cryopreserving ram
      epididymal spermatozoa, considering the decrease of sperm quality with post
      mortem time. Epididymal spermatozoa from 9 rams were kept at 5 degrees C using
      three storage methods: within the epididymes, undiluted sperm mass, and diluted
      in extenders of different osmolality (TES-Tris-fructose at 320, 370 or 420
      mOsm/kg, 20% egg yolk, 8% glycerol). At 0, 24, 48 and 72h, spermatozoa were
      cryopreserved using each extender. Samples were analyzed before and after
      cryopreservation by CASA (motility) and flow cytometry (viability and acrosomal
      status). Post-mortem time decreased pre-freezing and post-thawing sperm quality.
      Some storage x extender combinations improved the effect of post-mortem time on
      sperm quality. Both epididymis storage combined with the 420 extender, and
      storing the spermatozoa diluted in the 320 extender improved post-thawing
      quality, especially at long post-mortem times. Storing the spermatozoa diluted in
      the 370 extender was detrimental for the acrosomal status. These findings have
      practical applications. The simplest storage method (within the epididymes) seems
      to be adequate if hyperosmotic extenders were used for freezing. An alternative
      method could be storing the spermatozoa diluted in a hypoosmotic extender. These
      recommendations are limited to the osmolalities tested in this study (420 mOsm/kg
      and 320 mOsm/kg); other osmolalities should be tested.

PMID- 22137792
TI  - Acquired tracheal diverticulum as the cause of complicated orotracheal
      intubation.

PMID- 22137793
TI  - IV access difficulty: incidence and delays in an urban emergency department.
AB  - BACKGROUND: Intravenous access difficulty (IVAD) has long been recognized as a
      problem for emergency departments (ED), but epidemiologic data are lacking.
      OBJECTIVE: To estimate the incidence of IVAD and its associated delays in an
      urban ED. METHODS: We conducted this prospective cohort study in an urban ED at
      an academic medical center, enrolling adult patients who were likely to require
      an IV line. We recorded patients' history of IVAD and the time from the initial
      skin puncture to IV line establishment, noting the need for a second provider and
      the type of provider who was successful. We defined IVAD as follows: none,
      requiring a single skin puncture; mild, requiring multiple skin punctures;
      moderate, requiring a second non-physician provider; and severe, requiring a
      physician. We used descriptive statistics and calculated the relative risk (and
      95% confidence interval [CI]) for the association between prior IVAD and observed
      moderate or severe IVAD. RESULTS: We enrolled 125 patients, 107 of whom had an IV
      line placed in the ED. Their median age was 48 (interquartile range 38-60) years.
      The incidence and median delays associated with IVAD categories were as follows:
      none, 61%/1 min; mild, 11%/5 min; moderate, 23%/15 min; and severe, 5%/120 min.
      Prior IVAD was associated with a 2.5-fold greater risk of observed IVAD (95% CI
      1.3-4.7). CONCLUSION: In an urban, tertiary care ED, mild and moderate IVAD was
      common and led to mild delays, but severe IVAD, requiring a physician, caused
      substantial delays.

PMID- 22137795
TI  - Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma.
AB  - Tumor heterogeneity has been implicated in tumor growth and progression as well
      as resistance to therapy. We present an example of genetic heterogeneity in human
      malignant brain tumors in which multiple closely related driver genes are
      amplified and activated simultaneously in adjacent intermingled cells. We have
      observed up to three different receptor tyrosine kinases (EGFR, MET, PDGFRA)
      amplified in single tumors in different cells in a mutually exclusive fashion.
      Each subpopulation was actively dividing, and the genetic changes resulted in
      protein production, and coexisting subpopulations shared common early genetic
      mutations indicating their derivation from a single precursor cell. The stable
      coexistence of different clones within the same tumor will have important
      clinical implications for tumor resistance to targeted therapies.

PMID- 22137794
TI  - VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast
      cancer by engaging alpha4beta1-positive osteoclast progenitors.
AB  - Breast cancer patients often develop locoregional or distant recurrence years
      after mastectomy. Understanding the mechanism of metastatic recurrence after
      dormancy is crucial for improving the cure rate for breast cancer. Here, we
      characterize a bone metastasis dormancy model to show that aberrant expression of
      vascular cell adhesion molecule 1 (VCAM-1), in part dependent on the activity of
      the NF-kappaB pathway, promotes the transition from indolent micrometastasis to
      overt metastasis. By interacting with the cognate receptor integrin alpha4beta1,
      VCAM-1 recruits monocytic osteoclast progenitors and elevates local osteoclast
      activity. Antibodies against VCAM-1 and integrin alpha4 effectively inhibit bone
      metastasis progression and preserve bone structure. These findings establish VCAM
      1 as a promising target for the prevention and inhibition of metastatic
      recurrence in bone.

PMID- 22137796
TI  - Combined genetic inactivation of beta2-Microglobulin and CD58 reveals frequent
      escape from immune recognition in diffuse large B cell lymphoma.
AB  - We report that diffuse large B cell lymphoma (DLBCL) commonly fails to express
      cell-surface molecules necessary for the recognition of tumor cells by immune
      effector cells. In 29% of cases, mutations and deletions inactivate the beta2
      Microglobulin gene, thus preventing the cell-surface expression of the HLA class
      I (HLA-I) complex that is necessary for recognition by CD8(+) cytotoxic T cells.
      In 21% of cases, analogous lesions involve the CD58 gene, which encodes a
      molecule involved in T and natural killer cell-mediated responses. In addition to
      gene inactivation, alternative mechanisms lead to aberrant expression of HLA-I
      and CD58 in >60% of DLBCL. These two events are significantly associated in this
      disease, suggesting that they are coselected during lymphomagenesis for their
      combined role in escape from immune-surveillance.

PMID- 22137797
TI  - Vitamin K antagonists: self-determination by self-monitoring?

PMID- 22137800
TI  - CNS cavernous haemangioma: "popcorn" in the brain and spinal cord.
AB  - Cavernous haemangiomas (CH) are relatively uncommon non-shunting vascular
      malformations of the central nervous system and can present with seizures or with
      neurological deficits due to haemorrhage. Radiologists can often suggest the
      diagnosis of CH based on characteristic magnetic resonance imaging (MRI)
      features, thus avoiding further invasive procedures such as digital subtraction
      angiography or surgical biopsy. Although typical MRI appearance combined with the
      presence of multiple focal low signal lesions on T2*-weighted images or the
      presence of one or more developmental venous anomaly within the brain can improve
      the diagnostic confidence, serial imaging studies are often required if a
      solitary CH presents at a time when the imaging appearances had not yet matured
      to the typical "popcorn" appearance.

PMID- 22137799
TI  - Management of dermatitis in patients with locally advanced squamous cell
      carcinoma of the head and neck receiving cetuximab and radiotherapy.
AB  - Locally advanced squamous cell carcinoma of the head and neck is generally
      managed with a combination of surgery, RT, and/or chemotherapy or cetuximab.
      Appropriate management of radiation dermatitis associated with cetuximab and
      radiotherapy is necessary to allow adequate drug administration and to improve
      the quality of life and outcome. We generate a recommendation for radiation
      dermatitis on the basis of a systematic revision of the literature. Radiation
      dermatitis is experienced by the majority of patients undergoing radiotherapy for
      HNSCC, generally being mild to moderate (grades 1-2), showing about 25% severe
      toxicity (grade >= 3). Recommendations for prophylaxis and therapeutic
      interventions for each type of toxicity were proposed. This paper reviews
      comprehensive consensus guidelines to help manage the radiation dermatitis in
      order to make an optimal use of available therapeutic arsenal.

PMID- 22137798
TI  - Self-monitoring of oral anticoagulation: systematic review and meta-analysis of
      individual patient data.
AB  - BACKGROUND: Uptake of self-testing and self-management of oral anticoagulation
      [corrected] has remained inconsistent, despite good evidence of their
      effectiveness. To clarify the value of self-monitoring of oral anticoagulation,
      we did a meta-analysis of individual patient data addressing several important
      gaps in the evidence, including an estimate of the effect on time to death, first
      major haemorrhage, and thromboembolism. METHODS: We searched Ovid versions of
      Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised
      trials with a maximally sensitive strategy. We approached all authors of included
      trials and requested individual patient data: primary outcomes were time to
      death, first major haemorrhage, and first thromboembolic event. We did
      prespecified subgroup analyses according to age, type of control-group care
      (anticoagulation-clinic care vs primary care), self-testing alone versus self
      management, and sex. We analysed patients with mechanical heart valves or atrial
      fibrillation separately. We used a random-effect model method to calculate pooled
      hazard ratios and did tests for interaction and heterogeneity, and calculated a
      time-specific number needed to treat. FINDINGS: Of 1357 abstracts, we included 11
      trials with data for 6417 participants and 12,800 person-years of follow-up. We
      reported a significant reduction in thromboembolic events in the self-monitoring
      group (hazard ratio 0.51; 95% CI 0.31-0.85) but not for major haemorrhagic events
      (0.88, 0.74-1.06) or death (0.82, 0.62-1.09). Participants younger than 55 years
      showed a striking reduction in thrombotic events (hazard ratio 0.33, 95% CI 0.17
      0.66), as did participants with mechanical heart valve (0.52, 0.35-0.77).
      Analysis of major outcomes in the very elderly (age >=85 years, n=99) showed no
      significant adverse effects of the intervention for all outcomes. INTERPRETATION:
      Our analysis showed that self-monitoring and self-management of oral coagulation
      is a safe option for suitable patients of all ages. Patients should also be
      offered the option to self-manage their disease with suitable health-care support
      as back-up. FUNDING: UK National Institute for Health Research (NIHR) Technology
      Assessment Programme, UK NIHR National School for Primary Care Research.

PMID- 22137802
TI  - Beyond the short-term: clinical outcome and valve performance 2 years after
      transcatheter aortic valve implantation in 227 patients.
AB  - OBJECTIVE: Although the procedural feasibility of transcatheter aortic valve
      implantation has been shown by multiple groups, longer-term data are rare. We
      report on 2-year follow-up clinical and echocardiographic results after
      transcatheter aortic valve implantation in 227 patients. METHODS: Patients' mean
      age was 81 +/- 7 years, 59% were female, mean European System for Cardiac
      Operative Risk Evaluation was 21% +/- 14%, mean Society of Thoracic Surgeons
      score was 7% +/- 5%, and access routes were transfemoral (n = 164), transapical
      (n = 54), axillary (n = 5), or transaortic (n = 4). A CoreValve (Medtronic Inc,
      Minneapolis, Minn) prosthesis was implanted in 174 patients, and a SAPIEN
      prosthesis (Edwards Lifesciences, Irvine, Calif) was implanted in 53 patients.
      Clinical and echocardiographic investigations were performed at 6 months, 1 year,
      and 2 years. RESULTS: Survival was 88.5% at 30 days, 75.9% at 6 months, 74.5% at
      1 year, and 64.4% at 2 years. Patients improved significantly in New York Heart
      Association class after 6 months (from 3.2 +/- 0.5 to 1.7 +/- 0.7, P < .001) and
      up to 2 years (1.9 +/- 0.7). Cumulative incidences of myocardial infarction,
      stroke, and life-threatening or major bleeding were 2.7%, 6.2%, and 16.2% at 2
      years, respectively. The postprocedural mean transprosthetic gradient was 12 +/-
      4 mm Hg for all valves and did not change up to 2 years, and the effective
      orifice area was 1.5 +/- 0.4 cm2 with no change over 2 years of follow-up.
      Moderate or severe prosthetic regurgitation was present in 8% of patients at 2
      years. In 6% of patients, the paravalvular or valvular regurgitation grade
      increased significantly over time. CONCLUSIONS: With excellent functional
      recovery of the patients, good systolic valve function, and overall low morbidity
      at 2 years, transcatheter aortic valve implantation may be considered the
      treatment of choice for aortic valve stenosis in elderly patients with an
      increased risk for surgery with a heart-lung machine.

PMID- 22137803
TI  - Venovenous extracorporeal membrane oxygenation using a single cannula in patients
      with pulmonary hypertension and atrial septal defects.

PMID- 22137804
TI  - Strict versus liberal target range for perioperative glucose in patients
      undergoing coronary artery bypass grafting: a prospective randomized controlled
      trial.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that a liberal
      blood glucose strategy (121-180 mg/dL) is not inferior to a strict blood glucose
      strategy (90-120 mg/dL) for outcomes in patients after first-time isolated
      coronary artery bypass grafting and is superior for glucose control and target
      blood glucose management. METHODS: A total of 189 patients undergoing coronary
      artery bypass grafting were investigated in this prospective randomized study to
      compare 2 glucose control strategies on patient perioperative outcomes. Three
      methods of analyses (intention to treat, completer, and per protocol) were
      conducted. Observed power was robust (>80%) for significant results. RESULTS: The
      groups were similar on preoperative hemoglobin A(1c) and number of diabetic
      patients. The liberal group was found to be noninferior to the strict group for
      perioperative complications and superior on glucose control and target range
      management. The liberal group had significantly fewer patients with hypoglycemic
      events (<60 mg/dL; P < .001), but severe hypoglycemic events (<40 mg/dL) were
      rare and no group differences were found (P = .23). These results were found with
      all 3 methods of analysis except for blood glucose variability, maximum blood
      glucose, and perioperative atrial fibrillation. CONCLUSIONS: This study
      demonstrated that maintenance of blood glucose in a liberal range after coronary
      artery bypass grafting led to similar outcomes compared with a strict target
      range and was superior in glucose control and target range management. On the
      basis of the results of this study, a target blood glucose range of 121 to 180
      mg/dL is recommended for patients after coronary artery bypass grafting as
      advocated by the Society of Thoracic Surgeons.

PMID- 22137806
TI  - Creating an ideal "off-test mode" for rotary left ventricular assist devices:
      establishing a safe and appropriate weaning protocol after myocardial recovery.
AB  - OBJECTIVE: Recent developments in adjunctive therapy have enabled us to remove
      once-implanted left ventricular assist devices. For successful device removal,
      appropriate patient selection and precise evaluation of cardiac function are
      essential. However, with rotary pumps, pump weaning inevitably creates diastolic
      retrograde pump flow, and this flow may overload the native heart. We developed a
      novel "off-test mode" for weaning, which increases revolutions per minute just in
      diastole. The present study evaluated the effect of this mode on retrograde pump
      flow and ventricular workload. METHODS: The EVAHEART device (Sun Medical
      Technology Research Corporation, Nagano, Japan) was installed in 8 goats (63.0 +/
      7.3 kg). We evaluated myocardial oxygen consumption, pressure volume area, and
      retrograde pump flow under 3 conditions: circuit clamp, continuous mode, and off
      test mode. In continuous mode, revolution per minute was set for a mean net pump
      flow of zero, whereas in off-test mode, systolic revolution per minute was kept
      at a minimum level and diastolic revolution per minute was adjusted to ensure
      near-zero diastolic retrograde pump flow. RESULTS: In off-test mode, the pressure
      volume loop shapes were similar to those under circuit-clamp conditions, with
      both myocardial oxygen consumption and pressure volume area approximately equal
      to those under clamp conditions. Retrograde pump flow was significantly decreased
      in off-test compared with continuous mode (P = .005). CONCLUSIONS: Off-test mode
      decreased retrograde flow during weaning while keeping ventricular workload
      similar to baseline. This mode is potentially valuable for establishing a safe
      and appropriate pump weaning protocol after myocardial recovery. Investigations
      on heart failure models are ongoing.

PMID- 22137807
TI  - Building mental health literacy: opportunities and resources for clinicians.
AB  - Youth mental health is increasingly recognized as a key concern with significant
      impact on youth and society. School is the one setting where professionals are
      consistently available to monitor how children are functioning and learning and
      intervene and support. School psychiatry has expanded beyond individual mental
      health problems to school-wide and community issues including school violence,
      sexual harassment, bullying, substance abuse, discrimination, and discipline.
      This article describes the importance of mental health literacy in health
      outcomes and research in school-based mental health programs to better position
      the clinician to advocate at the individual and/or system level.

PMID- 22137808
TI  - International school mental health: global approaches, global challenges, and
      global opportunities.
AB  - School mental health programs from developed countries demonstrate that both the
      practice and research are becoming more important to policy makers, educators,
      health providers, parents, and other stakeholders. Some United Nations agencies
      and other international organizations have begun work to advance school mental
      health internationally. School-based mental health programming needs to be
      considered as part of usual child and youth mental health policies and plans,
      whether those are national or other jurisdictional in nature. Currently, a
      paucity of evidence-based and cost effective child and youth global mental health
      policies/programs exist, limiting school-based mental health programs being
      developed, implemented, or sustained.

PMID- 22137809
TI  - School law for the child psychiatrist: legal principles and case implications.
AB  - Schools are evolving to support all students, including those with mental health
      issues. Clinicians can help patients and schools by providing diagnostic clarity
      about a child's condition, how that condition interferes with school progress,
      and what interventions are needed in the school setting. State and Federal
      legislation supports timely response by schools to mental health issues emerging
      in students through special education laws and general education accommodations,
      such as Response To Intervention (RTI), which encourages schools to implement
      evidence-based interventions for students exhibiting mental health conditions.
      Case examples illuminate important legal considerations when clinicians are faced
      with issues such as therapeutic placements, home hospital forms, and substance
      abuse, and student misconduct.

PMID- 22137810
TI  - Spinning our wheels: improving our ability to respond to bullying and
      cyberbullying.
AB  - Bullying is physical and or psychological abuse perpetuated by one powerful child
      upon another, with the intention to harm or dominate. Bullying and aggression in
      schools has reached epidemic proportions. Abusive bullying behaviors begin in
      elementary school, peak during middle school, and begin to subside in high
      school. Bullying behaviors are associated with catastrophic violence.
      Cyberbullying has emerged as one result of the increasingly online social life in
      which modern teens and children engage. Mediation may be inappropriate. The only
      safety mechanism that children will ultimately retain is the one between their
      ears.

PMID- 22137811
TI  - When a student dies: organizing the school's response.
AB  - Principals, teachers, and guidance counselors feel ill-prepared to address a
      student's death. Often the death is not anticipated, comes as a shock, and has
      many reverberations in the school itself and in the broader community. The
      principal and others in the school may be called upon to serve as leaders in this
      sudden crisis and have broad responsibilities to their school community that may
      seem overwhelming in the face of their own grief and reactions to the loss. These
      guidelines present a meaningful response to an event that can profoundly affect
      the school and community.

PMID- 22137812
TI  - Building better brains: evidence-based interventions to enhance contemporary
      schooling.
AB  - School is a rich environment for cultivating academic skills, but also for
      developing metacognitive skills such as executive functioning and emotional
      regulation. However, the hours students spend in school are often guided by
      familiar practices rather than contemporary findings about how the brain best
      learns and grows. This article describes biological conditions favorable to brain
      development, psychological skills associated with effective school functioning,
      and school practices associated with academic and interpersonal success. The aim
      is that schooling might be shaped with regard to children's and adolescents'
      brain development needs rather than social custom.

PMID- 22137813
TI  - Maximizing the uptake and sustainability of school-based mental health programs:
      commercializing knowledge.
AB  - Clear benefits of school-based interventions focusing on health and mental health
      promotion or illness have been documented. A number of permanent repositories
      that rate and list effective school-based programs have been established.
      However, efforts to implement programs on a mass scale have not succeeded. There
      is a need to balance program development and improvement with uptake and
      implementation. This article outlines what is known about knowledge exchange and
      mobilization and introduces a business lens for school-based mental health
      programs uptake and sustainability. Individual clinicians can have significant
      impact by promoting strategies for both patients and the whole school population.

PMID- 22137814
TI  - Generalized anxiety disorder in the classroom.
AB  - Interventions for students with generalized anxiety disorder require attention to
      contextual factors both within and outside the classroom. They often are based on
      the principles of increasing environmental predictability and increasing the
      student's sense of self-efficacy. Good judgment is sometimes needed to determine
      which strategies constitute reasonable accommodations to the student's anxiety
      and which constitute an excessive deviation from usual school expectations. The
      latter can single out students unnecessarily or limit their academic progress.
      Working closely with parents and mental health professionals involved in the
      student's care is most likely to ensure a consistently helpful approach.

PMID- 22137815
TI  - Treating adolescents with social anxiety disorder in schools.
AB  - As is evident from the topic of this issue, schools can play an important role in
      addressing the unmet mental health needs of youth. Social anxiety disorder is
      particularly suited to being treated in the school setting. This article
      describes an empirically supported school-based intervention for social anxiety
      disorder, skills for academic and social success, and provides specific
      strategies to school counselors, teachers and community practitioners for
      implementing these methods. This article focuses on practical approaches for
      working with socially anxious adolescents in the school setting and how to
      increase awareness of social anxiety with parents and school personnel.

PMID- 22137817
TI  - Depression in the classroom: considerations and strategies.
AB  - Depression is a prevalent and debilitating disorder that can severely affect a
      young person's social, emotional, and academic functioning. Identifying
      depression early is essential to reducing the impact of this disorder. Depression
      is treatable. However, there are a number of classroom and school supports that
      can be put in place to assist a young person experiencing or recovering from
      depression. Preventing the development of depression through effective classroom
      programs should be encouraged and supported within the school environment.

PMID- 22137816
TI  - Responding to students with posttraumatic stress disorder in schools.
AB  - The prevalence of trauma exposure among youth is a major public health concern.
      Students who have experienced a traumatic event are at increased risk for
      academic, social, and emotional problems. School can be an ideal setting for
      mental health professionals to intervene with traumatized students, school staff,
      and parents both immediately following a traumatic event and when symptoms of
      posttraumatic stress disorder and other trauma-related mental health problems
      develop. This article describes evidence-based treatments for posttraumatic
      stress disorder and outlines practical approaches to use in schools.

PMID- 22137818
TI  - Strategies for implementing evidence-based psychosocial interventions for
      children with attention-deficit/hyperactivity disorder.
AB  - An extensive amount of research has demonstrated the effectiveness of
      psychosocial interventions for children with ADHD. Historically, the research has
      focused on interventions targeting problems in the home or school setting, but
      more recent research has highlighted the importance of family - school
      partnerships and conjoint approaches to intervention involving family and school.
      Effective approaches to psychosocial intervention consist of strategies to
      address performance deficits, promote adaptive behavior, and improve children's
      self-control and academic and social skills. Considerable evidence exists to
      indicate that combined approaches are more effective in reducing ADHD symptoms
      and related academic and social impairments than separate treatments.

PMID- 22137819
TI  - School-based interventions for disruptive behavior.
AB  - Youth disruptive behavior is a concern for youth, school personnel,families, and
      society. Early childhood disruptive behaviors negatively impact the classroom,
      and are associated with negative academic, social, behavioral, emotional,
      substance use, health, and justice system outcomes in adolescence and adulthood.
      Effective, comprehensive, multicomponent interventions targeting risk/protective
      factors and pathways associated with antisocial behavior reduce and/or mitigate
      these negative outcomes. Positive effects have been demonstrated for universal
      and indicated programs for participating youth and families in early childhood,
      and for high-risk youth in adolescence and young adulthood. These empirically
      supported programs inform the treatment of complex and difficult-to-treat
      disruptive behavior.

PMID- 22137820
TI  - Adolescent substance use disorders in the school setting.
AB  - Adolescent substance use is a major public health problem that concerns parents,
      schools, clinicians, and policy makers. The authors review school-based
      prevention programs, school drug policies, clinical signs and symptoms of
      substance impairment, recommendations for referral and engaging adolescents who
      are using substances, and treatment interventions for adolescent substance use
      disorders.

PMID- 22137821
TI  - Schooling students with psychotic disorders.
AB  - The term psychosis is generally used to describe the abnormal behaviors of
      children and adolescents with grossly impaired reality testing. This article
      discusses evaluation of psychotic symptoms in students and psychosocial school
      interventions for students with psychosis, including the roles of teachers and
      school administrators. Psychoeducation provided by clinicians and school staff to
      enhance coping and cognitive strategies is described.

PMID- 22137822
TI  - Evidence-based school psychiatry.

PMID- 22137823
TI  - Hepatocellular carcinoma within a noncirrhotic, nonfibrotic, seronegative liver:
      surgical approaches and outcomes.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) most commonly arises in patients with
      chronic liver disease. Data on outcomes after liver resection in patients with
      noncirrhotic, nonfibrotic, seronegative, referred to as a "normal" liver are
      limited. We aimed to investigate differences in prognostic factors and outcomes
      between patients presenting with HCC arising in "normal" liver (NLHCC) and that
      arising in "diseased" liver (DLHCC). STUDY DESIGN: All patients undergoing
      resection for HCC between 1994 and 2008 were assessed. Multivariable analysis of
      clincopathologic data from the NLHCC group was performed by comparing them with
      data from the group who had surgery for DLHCC during this period. RESULTS: During
      the 15-year study period, 142 patients underwent liver resection for HCC: 81 for
      NLHCC and 61 for DLHCC. NLHCCs were more often solitary but were larger and
      required more major resections. There was no significant difference in survival
      outcomes between patients who had NLHCC or DLHCC, with overall and recurrence
      free 5-year survivals of 60% and 51% in NLHCC and 55% and 33% in DLHCC,
      respectively. In patients with NLHCC, significant factors predicting overall
      survival were blood transfusion requirement (p = 0.003) and age (p = 0.009), and
      the only significant factor at predicting recurrence-free survival was presence
      of multiple tumors (p = 0.025). In contrast, in DLHCC, the only significant
      prognostic variables were a preoperative tumor biopsy (p = 0.017) or a high
      neutrophil-to-lymphocyte ratio (p = 0.001), both of which predicted a poorer
      recurrence-free survival. CONCLUSIONS: HCC presenting in patients with a normal
      background liver parenchyma appears to present a different spectrum of the
      disease. However, excellent outcomes can be achieved after liver resection,
      although this often requires the use of advanced techniques due to late
      presentation.

PMID- 22137824
TI  - Reduction in corticosteroids is associated with better health-related quality of
      life after liver transplantation.
AB  - BACKGROUND: Corticosteroid use during post-transplant immunosuppression
      contributes to documented long-term complications in liver transplant recipients.
      However, the effects of steroids on post-transplant physical and mental health
      related quality of life (HRQOL) have not been established. We aimed to test the
      association between steroid-based immunosuppression and post-transplant HRQOL in
      liver transplant recipients. STUDY DESIGN: We performed a retrospective analysis
      of prospective, longitudinal HRQOL measured using the Short Form 36 Health Survey
      physical and mental component summary scores, Beck Anxiety Inventory, and Center
      for Epidemiologic Studies Depression Scale. Steroid use (none, low [<10 mg/d],
      high [>=10 mg/d]) and temporally associated acute rejection (within previous 6
      weeks, previous 7 to 12 weeks, and never or >12 weeks before HRQOL measurement)
      were determined at every post-transplant HRQOL data point. Linear mixed-effects
      models tested the effects of contemporaneous steroid use and dosing on post
      transplant HRQOL. RESULTS: The sample included 186 adult liver transplant
      recipients (mean age 54 +/- 8 years, 70% male) with pre- and at least 1 post
      transplant HRQOL data point. Individual follow-up post-transplant averaged 21 +/-
      18 months (range 1 to 74 months). After controlling for pre-transplant HRQOL,
      time post-transplant, pre-transplant diagnosis group, and temporally associated
      episodes of rejection, post-transplant high-dose steroid use (>=10 mg/d) was
      associated with lower physical component summary (p < 0.001) and mental component
      summary (p = 0.049) scores and increased Beck Anxiety Inventory (p = 0.015)
      scores. Low-dose steroid use (<10 mg/d) was not associated with post-transplant
      HRQOL in any model (all p >= 0.28). CONCLUSIONS: High-dose steroid use for post
      transplant immunosuppression in liver transplant recipients was associated with
      reduced physical and mental HRQOL, and increased symptoms of anxiety. There was
      an association between better HRQOL and steroid reduction to <10 mg/d in liver
      transplant recipients during a broad follow-up period.

PMID- 22137825
TI  - An investigation of the fixation materials for cartilage frames in microtia.
AB  - When performing auriculoplasty for microtia surgery, wires are typically used to
      fix the costal cartilage frames. However, cases in which such wires become
      exposed during a long-term follow-up were frequently observed at our facility.
      Hence, using various materials, we conducted an investigation of the materials
      most suitable for fixation. METHOD: The subjects consisted of 122 cases in which
      auriculoplasty by costal cartilage graft surgery was performed and the
      postoperative course was traceable, within approximately 24 years from January
      1984 to March 2007. Regarding the fixation materials used in the 84 cases in
      which wire was used, 5 cases used monofilament non-absorbable sutures
      (Nylon((r))), 5 cases used monofilament absorbable sutures (PDS((r))), and 28
      cases used braided absorbable sutures(VICRYL((r))).Their postoperative course was
      investigated, and the presence of auricular deformities caused by a loosening of
      the fixation materials and the exposure of the fixation materials was examined.
      RESULTS: An exposure of the wire was observed in 19 cases (22.6%) of the 84 cases
      that used wires. An exposure of nylon was observed in 2 (40%) of 5 the cases that
      used nylon, and of those, a mild deformation was observed in the lower helix in
      one case that was suspected to have been caused by a loosening of the surgical
      suture. Regarding the 33 cases in which absorbable sutures were used (5 cases
      used monofilament absorbable sutures and 28 cases used braided absorbable
      sutures), neither any auricular deformities nor exposure of the fixation
      materials was observed in any of the cases. CONCLUSION: Whether using
      monofilament or braided sutures, absorbable sutures are therefore believed to be
      the most suitable material for the fixation of cartilage.

PMID- 22137826
TI  - Guideline for prophylactic feeding tube insertion in patients undergoing
      resection of head and neck cancers.
AB  - BACKGROUND: Supplementary nutrition is an important aspect of the
      multidisciplinary management of head and neck cancer patients. In our unit,
      method of feeding is based on an arbitrary predicted duration of overall
      treatment (<30 days indicates NG feeding, >30 days prophylactic PEG tube
      insertion is appropriate). This paper provides a guideline to assist in choosing
      the feeding method early on to avoid the need for later PEG insertion in those
      who were initially fed orally or via NG tube. PATIENTS AND METHODS: 59 patients
      undergoing resection of head and neck tumours were included, grouped according to
      their tumour stage and location. They were assessed pre- and post-operatively for
      5 years and their diet consistency score, method of supplementary feeding and
      weight were noted. RESULTS: Mean prophylactic PEG feeding duration was 771 days
      (N = 12), these patients mostly had T3/T4 tumours involving the tongue. Mean NG
      duration was 30.5 days (N = 42), 15 later had PEG insertion at mean 47 days post
      operatively, resulting in a total mean supplementary feeding duration of 579.6
      days. These patients tended to have higher stage tumours and poorer pre-operative
      diet consistency scores. 43 patients required post-operative radiotherapy. This
      significantly increased feeding duration versus surgery alone, and therefore
      increases the likelihood of requiring PEG insertion. CONCLUSIONS: Based on our
      findings, we have constructed an algorithm to assist in determining which
      patients with operable head and neck cancer should have prophylactic PEG tube
      insertion.

PMID- 22137829
TI  - Championing good health for people with disabilities.

PMID- 22137828
TI  - Oral health status in children with acute lymphoblastic leukemia.
AB  - Leukemia is a malignancy of the bone marrow. Acute lymphoblastic leukemia (ALL)
      is the most common pediatric malignancy and accounts for nearly 75% of all newly
      diagnosed leukemias and 25% of all malignancies in childhood. The aim of the
      present study was to review the oral health status in children with ALL.
      Databases were explored using various combinations of the following keywords:
      "acute lymphoblastic leukemia", "children", "inflammation", "pediatric",
      "periodontal disease" and "periodontitis". Oral inflammatory conditions including
      chelitis, gingivitis, herpetic gingivostomatitis, mucositis, oral candidiasis,
      periodontitis and ulcerations are common manifestations in children with ALL.
      RESULTS: Periodontal inflammatory conditions and oral mucositis were reported to
      be significantly higher in children with ALL as compared to healthy controls.
      Tooth morphological disorders including agenesis, microdontia, short roots and
      developmental defects in the enamel and dentin were more often observed in
      children with ALL as compared to healthy controls. Children with ALL have a
      reduced salivary flow rate, which makes them more susceptible to dental caries as
      compared to healthy children. Malocclusion due to microdontia may also trigger
      temporomandibular joint disorders in children with ALL; however, this
      relationship needs further investigations. CONCLUSION: Oral inflammatory
      conditions including mucositis and gingivitis are common in children with ALL as
      compared to healthy children. Tooth morphological disorders including microdontia
      and enamel and dentin are common manifestations in children with ALL.

PMID- 22137827
TI  - Missing: a diagnostic technique to enumerate antigen-specific T cells.
AB  - T lymphocytes are responsible for immune responses against pathogens, immune
      surveillance against cancer and maintenance of tolerance to self. While
      techniques available to detect antigen-specific T cells have been well described,
      there is a missing technique in our repertoire. While fluorescent multimers can
      be used for limited research applications, there is no existing technique
      suitable for detection of antigen-specific T cells in a diagnostic setting. The
      absence of such a technology has inhibited the search for "correlates of
      protection" against infectious, autoimmune or malignant disease. This critical
      review of existing methods will highlight the limitations of the data on which
      our current understanding of the immune system is based, in an effort to
      stimulate development of improved techniques.

PMID- 22137830
TI  - Political commitment for HIV/AIDS control in China.

PMID- 22137831
TI  - The Global Fund and a new modus operandi.

PMID- 22137832
TI  - The Commission on Macroeconomics and Health: was it the right recipe?

PMID- 22137833
TI  - Africa's health and the Commission on Macroeconomics and Health.

PMID- 22137835
TI  - Role of acute infection in HIV transmission.

PMID- 22137836
TI  - Role of acute infection in HIV transmission.

PMID- 22137838
TI  - Bivalirudin for patients with ST-elevation myocardial infarction.

PMID- 22137840
TI  - HPV vaccine in Rwanda: different disease, same double standard.

PMID- 22137841
TI  - Parenting resources matter.

PMID- 22137842
TI  - Primary health care and early childhood development.

PMID- 22137843
TI  - Quality of care in Japan: an additional strategy.

PMID- 22137844
TI  - Advocacy training and social accountability of health professionals.

PMID- 22137845
TI  - Cross-channel amplitude sweeps are crucial to speech intelligibility.
AB  - Classical views of speech perception argue that the static and dynamic
      characteristics of spectral energy peaks (formants) are the acoustic features
      that underpin phoneme recognition. Here we use representations where the
      amplitude modulations of sub-band filtered speech are described, precisely, in
      terms of co-sinusoidal pulses. These pulses are parameterised in terms of their
      amplitude, duration and position in time across a large number of spectral
      channels. Coherent sweeps of energy across this parameter space are identified
      and the local transitions of pulse features across spectral channels are
      extracted. Synthesised speech based on manipulations of these local amplitude
      modulation features was used to explore the basis of intelligibility. The results
      show that removing changes in amplitude across channels has a much greater impact
      on intelligibility than differences in sweep transition or duration across
      channels. This finding has severe implications for future experimental design in
      the fields of psychophysics, electrophysiology and neuroimaging.

PMID- 22137846
TI  - Synthesis and evaluation of macrocyclic diarylether heptanoid natural products
      and their analogs.
AB  - The macrocyclic diarylether heptanoid (MDEH) natural products have been used in
      folk medicine for centuries. MDEHs are reported to exert anti-tumor properties by
      inhibiting the activation of NF-kappaB. Here we report the synthesis of a small
      MDEH library (first reported synthesis of racemic platycarynol) using a Grubbs
      cross metathesis/Ullmann cyclization strategy. Evaluation of the library led to
      the identification of MDEH 9b which sensitizes pancreatic cancer cells to
      gemcitabine mediated growth inhibition and apoptosis.

PMID- 22137847
TI  - Design and diversity-oriented synthesis of novel 1,4-thiazepan-3-ones fused with
      bioactive heterocyclic skeletons and evaluation of their antioxidant and
      cytotoxic activities.
AB  - This study has achieved the design and diversity-oriented synthesis of novel 1,4
      thiazepine derivatives embedded with carbazole, pyrazole or isoxazole motif via
      microwave-assisted multicomponent reactions under solvent-free condition, thus
      providing a green and facile access to 1,4-thiazepine derivatives with prominent
      features of high structural diversity, short reaction time, high yields and
      environmental friendliness. More importantly, these novel compounds have been
      subjected to the test of in vitro antioxidant and cytotoxic activities, resulting
      in the finding that these 1,4-thiazepine derivatives not only have significant
      antioxidant activity, but also exhibit remarkably selective cytotoxicity to
      carcinoma cell line HCT 116.

PMID- 22137848
TI  - Synthesis of 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as platelet aggregation
      inhibitors.
AB  - Novel 2H-benzo[b][1,4]oxazin-3(4H)-ones have been synthesized by condensation,
      reduction, O-alkylation and Smiles rearrangement using 3-bromo-4-hydroxy
      benzaldehyde, anilines, and chloroacetyl chloride as starting materials. All the
      synthesized compounds have been characterized by (1)H NMR, (13)C NMR, and HRMS,
      and tested for the inhibitory ability on platelet aggregation. The results have
      shown that the ADP (adenosine 5'-diphosphate)-induced platelet aggregation was
      inhibited by 7a-g with the IC(50) value at 10.14-18.83 MUmol/L. Compound 7a
      exhibited the most potent inhibitory effect (IC(50)=10.14 MUmol/L) among all the
      compounds, but less potent than the control drug ticlopidine (3.18 MUmol/L) and
      aspirin (6.07 MUmol/L). The preliminary structure-activity relationship (SAR) was
      initially investigated in the study.

PMID- 22137849
TI  - Perceptions of teen motherhood in Australian adolescent females: life-line or
      lifederailment.
AB  - PURPOSE: The findings presented in this paper describe the beliefs and attitudes
      of three different groups of adolescent females about teen motherhood. These were
      elicited from a larger analysis that explored and theorized contraceptive
      pathways in a sample of young Australian women. METHODS: A purposive sample of
      females aged 14 to 19 years was recruited from three distinct populations in the
      city of Perth, Western Australia: (1) never-pregnant; (2) pregnant-terminated;
      and (3) pregnant-continued. Grounded theory principles were used to analyze data
      generated from 69 semi-structured interviews conducted over a 21 month period
      (2006-2008). RESULTS: Two categories that described teenagers' attitudes to
      pregnancy and motherhood were elicited from the analysis. These explained the
      level of priority that teenagers placed on using contraception and postponing the
      transition to parenthood. The category labeled 'life derailment' represented how
      those who had never had a pregnancy or had terminated a pregnancy constructed
      teen motherhood as potentially restricting their personal, career and social
      transition to adulthood. The alternative category, 'life-line', reflected how
      those who continued with their pregnancy perceived teen motherhood as a positive
      and transformative experience that fostered personal growth. CONCLUSIONS: The
      findings from this study contribute further insight into the complex nature of
      adolescent contraceptive use and pregnancy risk. The analysis has strengthened
      evidence of the critical role of self-perceptions of pregnancy and childbearing
      on teenagers' fertility outcomes. It has also emphasized the broader life
      circumstances that shape these attitudes, intentions and related behavior.
      Strategies directed toward academic support and vocational skill development may
      broaden teenage girls' perceived future options and achievement capacity, thus
      influencing key reproductive health outcomes.

PMID- 22137850
TI  - Comparative biodistribution of imaging agents for in vivo molecular profiling of
      disseminated prostate cancer in mice bearing prostate cancer xenografts: focus on
      111In- and 125I-labeled anti-HER2 humanized monoclonal trastuzumab and ABY-025
      affibody.
AB  - INTRODUCTION: Human epidermal growth factor receptor type 2 (HER2) overexpression
      supports proliferation of androgen-independent prostate cancer (PC). Radionuclide
      molecular imaging of HER2 expression in disseminated PC would aid in the
      selection of patients who are likely responders to HER2 targeting therapy. In
      this study, we evaluated whether ABY-025 Affibody molecule, a small (~ 7-kDa)
      HER2-binding scaffold protein, produces superior tumor-to-nontumor ratios
      compared with those obtained through the use of radiolabeled humanized anti-HER2
      antibody, trastuzumab. The influence of (111)In vs. (125)I radiolabel was
      evaluated for both tracers. METHODS: ABY-025 was labeled with (111)In using
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelator, site
      specifically coupled to the C-terminus via the maleimido derivative. Trastuzumab
      was labeled with (111)In using a CHX-A" diethylene triamine pentaacetic acid
      (DTPA) chelator. An indirect radioiodination with [(125)I]-N-succinimidyl-para
      iodobenzoate was used for both targeting proteins. Biodistribution of all labeled
      targeting proteins was evaluated in mice bearing DU-145 PC xenografts. RESULTS:
      The use of residualizing (111)In-label facilitated better tumor uptake and better
      tumor-to-nontumor ratios for both targeting agents. [(111)In]-ABY-025 provided
      tumor uptake of 7.1+/-0.8% injected dose per gram of tissue (% ID/g) and tumor-to
      blood ratio of 47+/-13 already at 6 h postinjection. The maximum tumor-to
      nontumor ratios with [(111)In]-CHX-DTPA-trastuzumab were achieved at 72 h
      postinjection, whereas tumor uptake was 11+/-4% ID/g and tumor-to-blood ratio was
      18+/-7. The biodistribution data were confirmed with gamma-camera imaging.
      CONCLUSIONS: Radiolabeled ABY-025 Affibody molecule provides higher contrast in
      imaging of HER2-expressing PC xenografts than radiolabeled trastuzumab.
      Residualizing radiometal label for ABY-025 provides better contrast in imaging of
      HER2-expressing PC xenografts than nonresidualizing radiohalogen.

PMID- 22137851
TI  - Supercritical carbon dioxide swelling of fluorinated and hydrocarbon surfactant
      templates in mesoporous silica thin films.
AB  - The penetration of compressed CO(2) in hydrocarbon and fluorocarbon regions of
      concentrated surfactant mesophases are interpreted from differences in the CO(2)
      processed pore expansion of mesoporous silica thin films templated by three
      surfactants containing varying degrees of hydrocarbon and fluorocarbon
      functionality. Ordered silica thin films are synthesized for the first time using
      the 16-carbon (C(16)) partly fluorinated surfactant,
      11,11,12,12,13,13,14,14,15,15,16,16,16-tridecafluorocetyl pyridinium bromide
      (HFCPB), as a templating agent. Silica films templated with surfactants
      containing a 8-carbon (C(8)) fluorocarbon tail (3,3,4,4,5,5,6,6,7,7,8,8,8
      tridecafluorooctyl pyridinium chloride (HFOPC)) and a 16-carbon (C(16))
      hydrocarbon tail (cetyl pyridinium bromide (CPB)) and HFCPB (C(16)) are processed
      in compressed CO(2) (69-172 bar, 25  degrees C and 45  degrees C) during
      synthesis. CO(2) processing results in significant pore expansion for films
      templated with both fluorinated surfactants, while pore expansion is negligible
      for the hydrocarbon templated material suggesting that preferential CO(2)
      penetration occurs in the 'CO(2)-philic' fluorocarbon segments of the surfactant
      template. The effect of substrate surface energy on the final uniformity of the
      dip-coated films is studied by varying the substrate from unmodified glass to a
      fluorocarbon-capped substrate. The ability to create dip-coated thin films on low
      surface energy substrates through favorable interaction of surfactant template
      tail with the substrate surface functional groups is demonstrated.

PMID- 22137852
TI  - Synthesis and properties of bisphenol A molecular imprinted particle for
      selective recognition of BPA from water.
AB  - Molecularly imprinted particle for bisphenol A (BPA-MIP) was prepared using the
      surface molecular imprinting technique with a sol-gel process on the surface of
      silica nanoparticles. The dosages of diethylenetriaminepentaacetic acid (DTPA) as
      a functional monomer and teraethyl orthosilicate (TEOS) as a cross-linker were
      optimized, respectively. The prepared BPA-MIP was characterized by scanning
      electron microscopy (SEM), energy dispersive spectrometer (EDS), Fourier
      transform infrared spectrometer (FTIR), thermogravimetric analysis (TGA), and a
      standard Brunauer-Emett-Teller (BET) analysis. Moreover, the proper binding and
      selective recognition ability were also investigated by a single batch binding
      experiment. The equilibrium data fitted well to the pseudo-second-order kinetic
      and the Langmuir model for BPA binding onto BPA-MIP, respectively. The saturate
      binding capacity of BPA-MIP was found to be 30.26 MUmol g(-1), which was three
      times higher than that of BPA non-molecular imprinted particle (BPA-NIP). The
      satisfactory results demonstrated that the obtained BPA-MIP showed an appreciable
      binding specificity toward BPA than similar structural compounds in water phase.
      The BPA-MIP could serve as an efficient selective material for determining or
      removing BPA from water environment.

PMID- 22137853
TI  - Self-organization at the interface and in aqueous solution of a cationic gemini
      surfactant from the dioctyl ester of cystine.
AB  - The cationic surfactant, dioctyl ester of cystine hydrochloride (DOEC), was
      characterized for interfacial adsorption and aggregation behavior in water. The
      cmc of DOEC was measured as 1.42+/-0.27*10(-5) mol dm(-3) using the techniques of
      tensiometry, conductivity and fluorimetry. From specific conductivity
      measurements, the degree of dissociation (alpha) of the amine hydrochloride was
      measured as 0.612. The standard free energy change of micellization (DeltaG(m)(
      degrees )) and adsorption (DeltaG(a)( degrees )) were calculated to be -25.07 and
      -44.37 kJ mol(-1), respectively. The aggregated structures provide non-polar
      microdomains as inferred from the I(3)/I(1) emission intensity ratio of 1.05 of
      pyrene fluoroprobe and also a blue shift of fluorescence emission wave length
      (lambda(emi.)) maximum down to 470 nm with enhanced intensity of ANS probe in
      micellar solutions. From Langmuir film balance experiments, it is shown that DOEC
      forms stable viscoelastic films at the interface with A(0) at 0.69 nm(2)molecule(
      1) that agree with the result from surface tension measurements. Molecular
      modeling suggests the tilted orientation of DOEC at the interface. A large
      packing parameter (P) of 0.58 and the fibril structures as observed from
      microscopy studies demonstrate that DOEC favors one-dimensional growth to form
      elongated micelles.

PMID- 22137854
TI  - Synthesis of poly(vinyl acetate-methyl methacrylate) copolymer microspheres using
      suspension polymerization.
AB  - Poly(vinyl acetate-methyl methacrylate) (VAc-MMA) copolymer microspheres were
      prepared using suspension polymerization at low temperature initiated with 2,2'
      azobis(2,4-dimethyl valeronitrile) (ADMVN). The poly(VAc-MMA) copolymer
      microspheres can be used over a large area where homopolymers, polyvinyl acetate
      (PVAc) and methyl methacrylate (PMMA) microspheres are capable of being put to
      use. The prepared microspheres were characterized by scanning electron microscopy
      (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and
      thermal gravimetric analysis (TGA). Obtained copolymer microspheres which have
      200 MUm average diameter and higher thermal stability than those of homopolymer.

PMID- 22137855
TI  - Removal of methylated arsenic using a nanostructured zirconia-based sorbent:
      process performance and adsorption chemistry.
AB  - A readily prepared nanostructured zirconia-based sorbent was developed and
      demonstrated to be effective on adsorption of monomethylarsonic acid (MMA) from
      water with a capacity of 1.43 mmol MMA/g sorbent, which is much higher than that
      of sorbents reported. It was found that the MMA uptake is highly pH-dependent.
      Better adsorption is obtained at lower pH, and the optimal pH is from 2.5 to 3.5.
      Most of the MMA uptake occurs rapidly in the first 48 h, followed by a relatively
      slow process. The adsorption kinetics and isotherm can be well described by
      pseudo-first order rate model and Langmuir equation, respectively. The
      temperature does not great influence on the adsorption isotherm. The MMA
      adsorption is independent on background electrolyte concentration, which implies
      the MMA forms inner-sphere complexes on the sorbent. The presence of humic acid
      does not pose noticeable effect on the adsorption. The coexisting HCO(3)(-) or F(
      ) obviously hinders the adsorption of MMA; however, the existence of PO(4)(3-)
      slightly enhances the adsorption. FTIR and XPS analyses demonstrated that
      hydroxyl and sulfur-containing functional groups are involved in the uptake of
      MMA. Based on the adsorption experimental results and spectroscopic analysis, an
      anion exchange mechanism is proposed for the adsorption of MMA.

PMID- 22137856
TI  - Headgroup effects on the Krafft temperatures and self-assembly of omega-hydroxy
      and omega-carboxy hexadecyl quaternary ammonium bromide bolaform amphiphiles:
      micelles versus molecular clusters?
AB  - Eight bolaform amphiphiles were synthesised and characterised; 4 alpha,omega
      hydroxy-alkane trialkyl (and pyridyl) ammonium bromides and 4 alpha,omega-carboxy
      alkane trialkyl (and pyridyl) ammonium bromides where the alkyl groups were
      methyl, ethyl and propyl. Four of these represented new compounds. Overall the
      Krafft temperatures (T(K)) of the eight amphiphiles were high, with 6 of the
      eight possessing T(K)s greater than 45  degrees C. Thus most of the amphiphiles
      could only expect to find applications at raised temperatures limiting their
      potential utility. However in addition to the previously reported alpha,omega
      hydroxy-hexadecyl triethylammonium bromide (2b) with a T(K) of 19.1  degrees C,
      another amphiphile, alpha,omega-carboxy-hexadecyl tripropylammonium bromide (2c)
      has been identified with a T(K) near ambient temperatures (T(K) of 22.1  degrees
      C). This provides an acid functional ammonium bolaform amphiphile that micellises
      at ambient temperatures to complement the hydroxyl derivative. A correlation
      between T(K) and the product of the enthalpies and T(m)s of the compounds was
      observed for 7 of the eight compounds. No correlation between the amphiphile
      critical micelle concentrations (cmc) and T(K)s was observed confirming previous
      reports that T(K) values are predominantly determined by crystalline stability
      rather than solubility. Considerable differences were observed between the
      various amphiphile T(K)s at different pHs but no clear trend was apparent for the
      various compounds (despite the degree to which the compounds' carboxylic acid and
      hydroxyl functionalities were likely to be ionised). The cmcs for the amphiphiles
      were an order of magnitude larger than those for analogous mono-ammonium
      amphiphiles with little difference in between the hydroxyl- and carboxy
      functionalised compounds. The aggregation numbers (N(agg)) obtained for all
      compounds were very low (N(agg)<7) and the apparent micellar diameters for the
      hydroxyl-bolaforms were in the range 1.0-1.4 nm whereas those for the carboxy
      compounds were in the range 2.1-2.4 nm. These results strongly suggest a
      difference in the packing of the two sets of amphiphiles with loose low density
      aggregates or 'molecular clusters' for the carboxy compounds and denser classical
      micellar type aggregates for the hydroxyl-compounds. In both cases however the
      sizes and the low aggregation numbers point suggest that these aggregates are
      more characteristic of the pre-micellar aggregates observed for many amphiphiles
      but in particular gemini surfactants.

PMID- 22137857
TI  - Synthesis of porous poly(styrene-co-acrylic acid) microspheres through one-step
      soap-free emulsion polymerization: whys and wherefores.
AB  - Synthesis of porous poly(styrene-co-acrylic acid) (PS-co-PAA) microspheres
      through one-step soap-free emulsion polymerization is reported. Various porous PS
      co-PAA microspheres with the particle size ranging from 150 to 240 nm and with
      the pore size ranging from 4 to 25 nm are fabricated. The porous structure of the
      microspheres is confirmed by the transmission electron microscopy measurement and
      Brunauer-Emmett-Teller (BET) analysis. The reason for synthesis of the porous PS
      co-PAA microspheres is discussed, and the phase separation between the
      encapsulated hydrophilic poly(acrylic acid) segment and the hydrophobic
      polystyrene domain within the PS-co-PAA microspheres is ascribed to the pore
      formation. The present synthesis of the porous PS-co-PAA microspheres is
      anticipated to be a new and convenient way to fabricate porous polymeric
      particles.

PMID- 22137858
TI  - Effects of poloxamer 407-induced hyperlipidemia on the pharmacokinetics of
      carbamazepine and its 10,11-epoxide metabolite in rats: Impact of decreased
      expression of both CYP3A1/2 and microsomal epoxide hydrolase.
AB  - The pharmacokinetics of carbamazepine (CBZ) and its active 10,11-epoxide
      metabolite (CBZ-E) were evaluated after intravenous and oral administration of 5
      mg/kg CBZ to rats with hyperlipidemia induced by poloxamer 407 (HL rats) and
      controls. The total area under the plasma concentration-time curve (AUC) of CBZ
      in HL rats after intravenous administration was significantly greater than that
      in controls due to their slower non-renal clearance (CL(NR)). This was due to
      slower hepatic CL(int) for metabolism of CBZ to CBZ-E in HL rats via CYP3A1/2.
      This result was consistent with a previous study indicating reduced hepatic
      CYP3A1/2 expression in HL rats. Interestingly, the AUC of CBZ-E was also
      increased in HL rats, while AUC(CBZ-E)/AUC(CBZ) ratios remained unchanged. These
      results suggested that further metabolism of CBZ-E to the inactive metabolite
      trans-10,11-dihydoxyl-10,11-dihydro-CBZ (CBZ-D) via microsomal epoxide hydrolase
      (mEH) was also slowed in HL rats. The significantly reduced hepatic mRNA level
      and expression of mEH protein in HL rats compared to controls confirmed the above
      hypothesis. Similar pharmacokinetic changes were observed in HL rats after oral
      administration of CBZ. These findings have potential therapeutic implications
      assuming that the HL rat model qualitatively reflects similar changes in patients
      with hyperlipidemia. Caution is required regarding pharmacotherapy in the
      hyperlipidemic state in cases where drugs that are metabolized principally by
      CYP3A1/2 or mEH and have a narrow therapeutic range are in use.

PMID- 22137859
TI  - Hematological clozapine monitoring with a point-of-care device: a randomized
      cross-over trial.
AB  - Clozapine remains the drug of choice for patients with treatment-resistant
      schizophrenia, who show a response rate of about 50% despite their
      unresponsiveness to other antipsychotics. Although treatment with clozapine can
      lead to considerable savings on bed days, the drug is underutilized for several
      reasons, perhaps most importantly because of the mandatory hematological
      monitoring. The Chempaq Express Blood Counter (Chempaq XBC) is a point-of-care
      device providing counts of white blood cells (WBC) and granulocytes based on a
      capillary blood sampling. A randomized cross-over trial design was used comparing
      capillary blood sampling using a point-of-care device with traditional venous
      blood sampling. Patients were randomized to two sequences starting with either
      capillary or venous blood sampling followed by a repeated sequence. Primary
      outcome was measured on a 10-cm visual analog scale. Eighty-five patients were
      included in the test. Eight (9.4%) dropped out before completion. Patients
      indicated that they found capillary blood monitoring less painful than venous
      sampling (VAS ratings: 0.55 cm 25-75 percentiles: 0.1-1.4 cm vs. 1.75 cm 25-75
      percentiles: 0.7-2.6, p<0.001). They also felt less inconvenienced by the point
      of-care method than the traditional blood sampling, which involved traveling to
      the laboratory clinical (0.3 cm 25-75 percentiles: 0.05-0.7 vs. 2.3 cm 25-75
      percentiles: 0.75-4.5, p<0.001). For hematological monitoring of clozapine
      patients a point-of-care device based on capillary blood sampling is better
      tolerated than traditional venous blood sampling.

PMID- 22137860
TI  - Self-reported physical and mental health of older adults: the roles of caregiving
      and resources.
AB  - OBJECTIVES: This study examined factors associated with self-reported physical
      and mental health, focusing on caregiving status and the availability of social
      supports and financial resources. METHODS: Two bivariate analyses were performed
      to examine the sociodemographic characteristics as well as perceived health
      outcomes among caregiving and non-caregiving participants. Two-equation probit
      models were used to determine independent predictors of self-reported physical
      and mental health, using data from 1071 community-based adults (>= 60 years). An
      additional bivariate analysis was conducted to investigate the characteristics of
      caregivers who reported better physical health. RESULTS: Approximately 17%
      (n=183) of respondents reported being caregivers, and those in caregiving roles
      tended to be ethnic minorities, married, and have telephone communication with
      family or friends on a daily basis. Better physical and mental health outcomes
      were common for caregivers and non-caregivers who reported having more resources
      (e.g., higher income, better preparedness for future financial need, higher
      satisfaction with transportation and housing, and no limitation of usual daily
      activities). However, sociodemographic and social support factors were not
      significantly associated with physical and mental health among caregivers, unlike
      their non-caregiver counterparts. In the probit model, caregivers were more
      likely to be physically healthy compared to non-caregivers (Coefficient=0.34; p
      value=0.031). Compared with healthy non-caregivers (n=631), healthy caregivers
      (n=141) tended to be ethnic minorities, married, and have telephone communication
      with family or friends on a daily basis. CONCLUSIONS: Findings suggest that
      preparing resources and maintaining strong social support systems may foster
      health status among older family caregivers.

PMID- 22137861
TI  - Risk-taking behavior in skiing among helmet wearers and nonwearers.
AB  - OBJECTIVE: To examine differences in on-the-snow ski behavior between helmet
      wearers and nonwearers. METHODS: The data were collected using a survey. Several
      tourist agencies helped in administrating the survey to the skiers during the
      2008-2009 and 2009-2010 seasons. The survey consisted of multiple-choice
      questions. The subjects were asked to choose answers most suitable for their
      skiing style and preferred skiing technique, volume of off-piste skiing,
      readiness to use time measuring systems on the slopes, and group-skiing
      preferences, such as leading the group, beside the group, away from the group,
      etc. The Risk Index was then calculated for each subject. RESULTS: The answers of
      710 skiers (mean age 35.5, range 16-81 years) were analyzed. The predictive power
      for risk-taking behavior was tested for gender, age, educational level, level of
      skiing, years of skiing, and helmet usage. Younger age, male gender, higher
      skiing level, and helmet usage were used as independent predictors for the
      overall Risk Index (Power [1-beta err prob] = 0.942). Significantly higher risk
      was assessed for the male helmet wearers while the results were not significant
      for the female helmet wearers. The male occasional helmet wearers were found to
      be the most prone to risky behavior. In female nonhelmet wearers, there was a
      significant decrease in risk-taking behavior with age but this was not true for
      female helmet wearers. CONCLUSIONS: For males under 35 years of age, helmet use
      is one of the factors influencing risk-taking on the slopes. This is demonstrated
      for occasional helmet wearers in particular.

PMID- 22137862
TI  - Fighting in thin air: operational wilderness medicine in high Asia.
AB  - OBJECTIVE: The current conflict in Afghanistan is the first major military action
      in which the United States and other North Atlantic Treaty Organization (NATO)
      forces have found themselves regularly engaged in combat at high altitudes.
      However, high altitude warfare is not a new concept in Asia by any means.
      METHODS: This article will offer a short general historical review of high
      altitude warfare in Asia and then specifically address some of the operational
      challenges faced by troops carrying out missions at high altitude in the ongoing
      conflict in Afghanistan. Additionally, there will be discussion of evidence-based
      interventions being used to attempt to maintain optimal health of the warfighter
      at high altitude in this theater of operations. CONCLUSIONS: Years of research
      into how to alleviate the problematic nature of military operations in the high
      altitude environment has resulted in extensive risk management recommendations
      from the US Army, specifically aimed at preventing altitude-related casualties.

PMID- 22137863
TI  - A blinded, randomized, palatability study comparing variations of 2 popular field
      water disinfection tablets.
AB  - OBJECTIVE: Halogen-based water disinfection tablets may render an unpleasant
      taste to treated water. Proposed safe additives such as ascorbic acid may reduce
      this objectionable taste. We compared the palatability of 2 field water
      disinfectants: iodine-based tetraglycine hydroperiodide (TGHP) and chlorine-based
      chlorine dioxide (CD) both with and without the concomitant use of an ascorbic
      acid taste neutralizer. METHODS: Blinded participants randomly sampled 5
      different distilled water samples containing combinations of disinfectant tablets
      and ascorbic acid: 1) water; 2) water with TGHP; 3) water with CD; 4) water with
      TGHP plus ascorbic acid; and 5) water with CD plus ascorbic acid. Participants
      rated beverage taste via a 100 mm visual analogue scale (VAS) and ranked the
      samples from "most pleasant" to "least pleasant." RESULTS: Sixty participants
      evaluated the samples. On the VAS, water with TGHP tasted worst and water with CD
      tasted second worst. Water with TGHP plus ascorbic acid, water alone, and water
      with CD plus ascorbic acid measured similarly as significantly best tasting.
      Water with TGHP was ranked by 58% as "least pleasant" tasting, while water with
      TGHP and ascorbic acid was ranked by 40% as "most pleasant" tasting. CONCLUSIONS:
      Participants found halogen-based disinfected water significantly less palatable
      prior to the addition of ascorbic acid. Addition of ascorbic acid to treated
      water created a beverage of similar preference to distilled water. These results
      may increase compliance with the use of disinfecting tablets by increasing the
      palatability of drinking water made potable via addition of ascorbic acid to
      halogen-based chemical disinfection.

PMID- 22137864
TI  - Because it's there... The education of George Mallory.
AB  - Initiative, creativity, and resolve represent both the pillars of the Wilderness
      Medical Society (WMS) and the story of George Mallory. His journey from humble
      beginnings to his rise to become one of history's most legendary mountaineers is
      a testament to the impact of great mentors as well as the development of Mallory
      as a mentor himself. In this light, the path of George Mallory in mountaineering
      and the role of WMS in wilderness medicine share a common theme. This essay is
      not only a tribute to George Mallory but also a testament to the importance of
      mentorship and the role of WMS in inspiring mentorship and education to future
      pioneers.

PMID- 22137869
TI  - Alterations in the extracellular catabolism of nucleotides are involved in the
      antiproliferative effect of quercetin in human bladder cancer T24 cells.
AB  - Bladder cancer is the most prevalent tumor in the genitourinary tract and the
      current treatments are not efficient to prevent recurrence and progression of
      tumor cases. Studies have revealed evidence of the involvement of the purinergic
      system in bladder tumorigenesis, particularly ecto-5'-NT/CD73, the enzyme
      responsible for AMP hydrolysis. Quercetin (3,3',4',5,7-pentahydroxyflavone) is a
      plant-derived flavonoid that has been shown to exert a broad range of
      pharmacologic properties, including potential anticancer activity. Here, we
      investigated the quercetin effect on the E-NTPDases and ecto-5'
      nucleotidase/CD73, which catalyzes the introversion of the extracellular purine
      nucleotides in T24 human bladder cancer cells. The results showed that this
      flavonoid was able to increase ADP hydrolysis and inhibit the ecto-5'
      nucleotidase/CD73 activity, with no effect on protein expression. The treatment
      with APCP (alpha,beta-methyleneadenosine-5'-diphosphate), another ecto-5'-NT/CD73
      inhibitor, led to a significant reduction in cell proliferation. In addition, we
      showed that AMP, which can be accumulating by enzyme inhibition, had an
      antiproliferative effect on T24 cells, which was enhanced when its hydrolysis was
      inhibited by APCP treatment. Otherwise, adenosine did not cause any significant
      effect on cell proliferation and the quercetin effects were not altered by the
      simultaneous presence of adenosine. Taken together, the results suggest that the
      antiproliferative effect of quercetin on tumor cells may occur, at least in part,
      via alterations in the extracellular catabolism of nucleotides, that could be by
      AMP accumulation, or could be due to blocked adenosine receptors by this
      flavonoid, supporting the potential use of quercetin in bladder cancer treatment.

PMID- 22137871
TI  - The management of soft tissue sarcomas.
AB  - BACKGROUND: Soft tissue sarcomas are a rare and heterogenous group of
      malignancies that are derived from the mesenchymal cell lines. In the last few
      decades, the management of these lesions has been improved by the introduction of
      dedicated Multi Disciplinary Teams (MDTs) where most bone and soft tissue tumours
      are now treated.(1) Following the recent changes to management outlined by the
      NICE/IOGs, we believe it is pertinent to review the current thinking on soft
      tissue tumour management.(2) We also discuss the principles of diagnosis and
      treatment and the role of adjuvant therapy. METHODS: This is a retrospective
      review. In the preparation of this paper, we have referred to recent NICE
      guidelines in this field and have performed a Medline search of the existing
      literature. RESULTS: The key to the success is early and appropriate patient
      referral. Whilst the responsibility for performing surgery has shifted away from
      the generalist and towards the super specialist, improvements in survivability
      can be achieved by promoting basic knowledge within the medical profession as a
      whole. CONCLUSIONS: Both excision and biopsy of a soft tissue sarcoma by a non
      specialist surgeon have been shown to increase the risk of tumour recurrence and
      all invasive procedures should now be performed within the MDT setting.

PMID- 22137870
TI  - Is prostate-specific antigen percentage decrease predictive of clinical outcome
      after permanent iodine-125 interstitial brachytherapy for prostate cancer?
AB  - OBJECTIVE: To determine the usefulness of prostate-specific antigen (PSA)
      percentage (vs. pretreatment value assumed as 100%) in prediction of biochemical
      relapse, after iodine-125 ((125)I) permanent brachytherapy for prostate cancer,
      to employ a parameter independent by the initial PSA amount and by the individual
      prostatic volume. METHODS AND MATERIALS: Our study included 133 patients, 102
      still disease free (Group A) and 31 who experienced proven biochemical recurrence
      (Group B). PSA levels before and after (125)I brachytherapy were recorded, and
      PSA percentage vs. pretreatment values were calculated. Cox regression model,
      receiver operating characteristic curves, and Kaplan-Meier regression model with
      log-rank test were calculated. RESULTS: We observed that, in patients submitted
      to brachytherapy for prostate cancer, a PSA percentage >20% of pretreatment value
      is highly associated with relapse risk (p<0.0001) and that this association is
      strongly present since t=6 months of followup (p<0.0001), with a hazard ratio
      near to five times (4.965), a sensitivity of 72.4%, and specificity of 79.8%
      related to the chosen cutoff. DISCUSSION: Despite the amount of PSA is the only
      parameter that the clinicians can deploy to monitor patient's followup after
      permanent interstitial brachytherapy for prostate cancer, its evolution in time
      seems unable to predict early biochemical relapse as it is influenced by
      prostatic volume and initial PSA amount. CONCLUSIONS: Our data suggest that a PSA
      percentage >20% of pretreatment value at 6 months might represent an early,
      inexpensive, and useful predictive tool of bad outcome in patients after
      permanent brachytherapy.

PMID- 22137872
TI  - Malnutrition and heart failure: comments.

PMID- 22137873
TI  - MRCP and 3D LAVA imaging of extrahepatic cholangiocarcinoma at 3 T MRI.
AB  - Extrahepatic cholangiocarcinoma (CCA) is a primary bile duct malignant tumour
      with poor prognosis. Familiarity with their varied imaging characteristics can be
      helpful in developing a correct diagnosis and in optimal treatment planning, and
      thus contribute to a better prognosis. The purpose of this article is to
      illustrate the typical appearances of extrahepatic CCA on magnetic resonance
      cholangiopancreatography (MRCP) and three-dimensional (3D) LAVA (liver
      acquisition with volume acceleration) sequences at 3 T magnetic resonance imaging
      (MRI), and to discuss the superiority of the two techniques in the diagnosis of
      CCA.

PMID- 22137874
TI  - What influences the impact of pressure ulcers on health-related quality of life?
      A qualitative patient-focused exploration of contributory factors.
AB  - With the recognition of health-related quality of life (HRQL) as an important and
      relevant outcome in pressure ulceration, it is important to gain better
      understanding of the complex relationship among the various factors that affect
      it. A problem with existing literature in this area is that the impact of having
      a pressure ulcer on HRQL is combined conceptually with contributory factors which
      may influence outcome. This study identified contributory factors affecting
      pressure ulcer-related HRQL and explored interrelationships between factors based
      on views of adults with pressure ulcers. We obtained patient-reported qualitative
      data through semi-structured interviews with 30 patients with pressure ulcers
      recruited from hospital and community settings around England and Northern
      Ireland. Patients described how pressure ulcers affected their lives by
      recounting specific relevant events. Events (patient-reported issues) were sorted
      into categories and data framework analysed to produce a taxonomy of contributory
      factors. Inter-rater reliability established the extent of agreement between two
      independent raters. We identified 16 contributory factors, into two theme
      taxonomy: experience-of-care and individual-patient factors, defined by
      descriptive components. Our taxonomy is a comprehensive theoretical model of
      factors that contribute to pressure ulcer-related HRQL. We have also identified
      further research priorities to inform clinical practice.

PMID- 22137875
TI  - Dermatomyositis and meningioma in the same patient.
AB  - The association between dermatomyositis (DM) and neoplasm has been widely
      described, especially in elder patients; this entity can be associated with many
      different types of tumours, more frequently lung, ovary, and gastric cancers.
      There is no clear association with central nervous system tumours. We present the
      case of a 64-year-old woman diagnosed simultaneously of DM with a difficult
      clinical control and a meningioma, being the course of the two illnesses linked.
      The activity of the DM was controlled after the meningioma was removed.

PMID- 22137876
TI  - Characterization of a new highly mosquitocidal isolate of Bacillusthuringiensis-
      an alternative to Bti?
AB  - The mosquito is a very important vector involved in the worldwide transmission of
      disease-causing viruses and parasites. Controlling the mosquito population
      remains one of the best means for preventing the serious infectious diseases of
      malaria, yellow fever, dengue, filariasis and so on and there has been an
      increasing interest in developing biopesticides as a useful substitute to
      chemical insecticides. As a result, Bacillus thuringiensis subsp. israelensis
      (Bti) has been extensively used due to its specificity and high toxicity to a
      variety of mosquito larvae. However it is prudent to seek alternatives to Bti
      with alternative spectra of mosquitocidal activity or that are able to overcome
      any resistance that might develop against Bti. The Bt S2160-1 strain was isolated
      from soil samples collected from Southern China and found to have a comparable
      mosquitocidal activity to Bti. However there were significant differences in
      terms of their plasmid profiles, crystal proteins produced and cry gene
      complement. A PCR-restriction fragment length polymorphism identification system
      was developed and used in order to identify novel cry-type genes and four such
      genes (cry30Ea, cry30Ga, cry50Ba and cry54Ba) were identified in Bt S2160-1. In
      conclusion, Bt S2160-1 has been identified as a potential alternative to Bti,
      which could be used for the control of mosquito populations in order to reduce
      the incidence of mosquito-borne diseases.

PMID- 22137877
TI  - The bacterium, Lysinibacillus sphaericus, as an insect pathogen.
AB  - Since the first bacteria with insecticidal activity against mosquito larvae were
      reported in the 1960s, many have been described, with the most potent being
      isolates of Bacillus thuringiensis or Lysinibacillus sphaericus (formerly and
      best known as Bacillus sphaericus). Given environmental concerns over the use of
      broad spectrum synthetic chemical insecticides and the evolution of resistance to
      these, industry placed emphasis on the development of bacteria as alternative
      control agents. To date, numerous commercial formulations of B. thuringiensis
      subsp. israelensis (Bti) are available in many countries for control of nuisance
      and vector mosquitoes. Within the past few years, commercial formulations of L.
      sphaericus (Ls) have become available. Because Bti has been in use for more than
      30 years, its properties are well know, more so than those of Ls. Thus, the
      purpose of this review is to summarise the most critical aspects of Ls and the
      various proteins that account for its insecticidal properties, especially the
      mosquitocidal activity of the most common isolates studied. Data are reviewed for
      the binary toxin, which accounts for the activity of sporulated cells, as well as
      for other toxins produced during vegetative growth, including sphaericolysin
      (active against cockroaches and caterpillars) and the different mosquitocidal Mtx
      and Cry toxins. Future studies of these could well lead to novel potent and
      environmentally compatible insecticidal products for controlling a range of
      insect pests and vectors of disease.

PMID- 22137878
TI  - Maternal determinants of complete child immunization among children aged 12-23
      months in a southern district of Nigeria.
AB  - This study was conducted to identify determinants of complete immunization status
      among children aged 12-23 months in a southern district of Nigeria. The World
      Health Organization cluster survey was used to evaluate immunization coverage of
      infants. Mothers of 525 children selected by the two-stage sampling method and
      interviewed using an adapted questionnaire responded. Completion of the
      immunization schedule was verified by an immunization card or by reported history
      indicating that the child had received full doses of four of the antigens
      included in the Nigeria routine immunization schedule. Multivariate logistic
      regression was used to identify factors associated with completion of
      immunization. Only 32.4% of children had completed the immunization schedule.
      Determinants of complete immunization status included a maternal age less than 30
      years (AOR=2.26, 95% CI:1.27-4.03), availability of an immunization card at first
      contact (AOR=7.72, 95% CI:4.43-13.44), fewer than three children (AOR=2.22, 95%
      CI:11.1-4.42), completion of post secondary education (AOR=2.34, 95% CI:1.12
      4.47) and maternal unemployment (AOR=1.71, 95% CI:1.01-2.89). Identifying mothers
      whose children are at risk of not completing the immunization schedule and
      educating them is an important strategy to improve antigen coverage and prevent
      early childhood deaths from diseases like tuberculosis, poliomyelitis, tetanus,
      diphtheria, pertussis and measles.

PMID- 22137879
TI  - Effects of a nationwide Hib vaccine shortage on vaccination coverage in the
      United States.
AB  - BACKGROUND: A shortage of Haemophilus influenzae type b (Hib) vaccine that
      occurred in the United States during December 2007 to September 2009 resulted in
      an interim recommendation to defer the booster dose, but to continue to vaccinate
      as recommended with the primary series during the first year of life. OBJECTIVES:
      To quantify effects of the Hib shortage on vaccination coverage and to determine
      if any demographic subgroups were disproportionately affected. METHODS: Data from
      the 2009 National Immunization Survey (NIS) were divided based on child's age at
      the onset of the shortage. Comparisons were made in primary series coverage by 9
      months between children <7 months versus >=7 months at the start of the shortage.
      Comparisons in primary series plus booster dose completion by 19 months were made
      between children who were <12 months versus >=12 months at the start of the
      shortage. RESULTS: Nationally, there was a difference in Hib primary series
      completion by 9 months among children age <7 months versus >=7 months at the
      start of the shortage (73.9% versus 81.2%, P<0.001). There was a large difference
      in the percentage of children fully vaccinated with the primary series plus
      booster dose by 19 months among children age <12 months versus >=12 months at the
      start of the shortage (39.5% versus 66.0%, P<0.001). There were differential
      effects of the shortage on primary series coverage among states and for some
      demographic characteristics. CONCLUSIONS: As expected booster dose coverage was
      reduced consistent with interim recommendations, but primary series coverage was
      also reduced by 7 percentage points nationally.

PMID- 22137880
TI  - Malignant potential of pleomorphic xanthoastrocytoma.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a low-grade astrocytic tumour that
      occasionally progresses to a higher grade. We have extensively reviewed the
      literature on the potential for malignant transformation of PXA. An illustrative
      case of a PXA transforming to glioblastoma multiforme is presented.

PMID- 22137881
TI  - The knife and gun club just adjourned: managing penetrating injuries in the
      emergency department.

PMID- 22137882
TI  - Woman with risks for torsades de pointes dying within hours of leaving the
      emergency department.

PMID- 22137883
TI  - Prehospital electrocardiography: a review of the literature.
AB  - INTRODUCTION: The American Heart Association and other scientific guidelines
      recommend emergency medical services acquire prehospital (PH) electrocardiography
      (ECG) in all patients with symptoms of acute coronary syndrome. The purpose of
      this article is to critically review the scientific literature about PH ECG.
      METHODS: Using multiple search terms, we searched the PubMed and Web of Science
      databases for relevant information. Search limiters were used: human, research
      (clinical trials, experimental), core journals, and adult. All articles about the
      clinical effects of PH ECG published between 2001 and 2011 were retained, in
      addition to a landmark study from 1997. RESULTS: Our search yielded a total of
      105 articles when all years of publication were considered. When the same search
      was limited to articles published between 2001 and 2011 for new and current data,
      45 articles were returned. A total of 7 articles about the clinical effects of PH
      ECG were retained for this review. Articles were conceptualized and organized by
      clinical effects of PH ECG (timing, reperfusion rate, death, ejection fraction,
      reinfarction, and stroke). PH ECG has been associated with reduced PH delay time,
      increased use of reperfusion interventions, earlier diagnosis, and faster time to
      treatment. DISCUSSION: PH ECG plays a major role in emergency cardiac systems of
      care and can facilitate early intervention by identifying patients with acute
      coronary syndrome sooner.

PMID- 22137884
TI  - Bacterial host interactions in cystic fibrosis.
AB  - Chronic infection is a hallmark of cystic fibrosis (CF) and the main contributor
      to morbidity. Microbial infection in CF is complex, due to the number of
      different species that colonise the CF lung. Their colonisation is facilitated by
      a host response that is impaired or compromised by highly viscous mucous, zones
      of hypoxia and the lack of the cystic fibrosis transmembrane regulator (CFTR).
      Successful dominant CF pathogens combine an effective arsenal to establish
      infection and counter-attack the host response, together with an ability to adapt
      readily to an unfavourable environment. Hypermutability is common among CF
      pathogens facilitating adaptation and as the host response persists, progressive
      destruction of the normal architecture of lung tissue ensues with catastrophic
      consequences for the host.

PMID- 22137885
TI  - Host-pathogen interactions between the skin and Staphylococcus aureus.
AB  - Staphylococcus aureus is responsible for the vast majority of bacterial skin
      infections in humans. The propensity for S. aureus to infect skin involves a
      balance between cutaneous immune defense mechanisms and virulence factors of the
      pathogen. The tissue architecture of the skin is different from other epithelia
      especially since it possesses a corneal layer, which is an important barrier that
      protects against the pathogenic microorganisms in the environment. The skin
      surface, epidermis, and dermis all contribute to host defense against S. aureus.
      Conversely, S. aureus utilizes various mechanisms to evade these host defenses to
      promote colonization and infection of the skin. This review will focus on host
      pathogen interactions at the skin interface during the pathogenesis of S. aureus
      colonization and infection.

PMID- 22137886
TI  - Cotinine enhances the extinction of contextual fear memory and reduces anxiety
      after fear conditioning.
AB  - Posttraumatic stress disorder (PTSD) is an anxiety disorder triggered by
      traumatic events. Symptoms include anxiety, depression and deficits in fear
      memory extinction (FE). PTSD patients show a higher prevalence of cigarette
      smoking than the general population. The present study investigated the effects
      of cotinine, a tobacco-derived compound, over anxiety and contextual fear memory
      after fear conditioning (FC) in mice, a model for inducing PTSD-like symptoms.
      Two-month-old C57BL/6J mice were separated into three experimental groups. These
      groups were used to investigate the effect of pretreatment with cotinine on
      contextual fear memory and posttreatment on extinction and stability or
      retrievability of the fear memory. Also, changes induced by cotinine on the
      expression of extracellular signal-regulated kinase (ERK)1/2 were assessed after
      extinction in the hippocampus. An increase in anxiety and corticosterone levels
      were found after fear conditioning. Cotinine did not affect corticosterone levels
      but enhanced the extinction of contextual fear, decreased anxiety and the
      stability and/or retrievability of contextual fear memory. Cotinine-treated mice
      showed higher levels of the active forms of ERK1/2 than vehicle-treated mice
      after FC. This evidence suggests that cotinine is a potential new pharmacological
      treatment to reduce symptoms in individuals with PTSD.

PMID- 22137887
TI  - Autoantibodies in primary Sjogren's syndrome patients induce internalization of
      muscarinic type 3 receptors.
AB  - OBJECTIVES: Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease
      characterized by lymphocyte infiltration into the salivary and lachrymal glands,
      leading to dry mouth and eyes. The presence of functional autoantibodies against
      muscarinic type 3 receptor (M3R) has been reported in pSS patients. However, the
      pathological role of anti-M3R autoantibodies in pSS salivary dysfunction remains
      controversial. METHODS: Purified IgGs were obtained from normal (control) and
      primary SS patients' sera (pSS IgG). Internalization of M3R and clathrin was
      analyzed by biochemical assay and immunofluorescence confocal microscopy using
      human submandibular gland (hSMG) cells. Cytoplasmic free Ca(2+) concentration
      ([Ca(2+)](i)) was measured by microspectrofluorimetry. RESULTS: Incubation of
      hSMG cells with pSS IgG (1mg/ml) significantly decreased M3R expression levels at
      the membrane. Carbachol-induced [Ca(2+)](i) transients (CICTs) in these cells
      were also inhibited by pSS IgG. In contrast to pSS IgG, control IgG had no effect
      on both the M3R expression level and CICTs. We found that binding of pSS IgG to
      M3R induces phosphorylation of the receptor, and that the pSS IgG-induced M3R
      internalization is prevented by the lysosomal inhibitor, chloroquine. In
      addition, pSS IgG decreased membrane clathrin expression, which was inhibited by
      atropine. Our immunofluorescence study further confirmed that pSS IgG induces a
      co-localization of M3R with clathrin and subsequent internalization of M3R.
      CONCLUSION: pSS IgG induces internalization of M3R partly through a clathrin
      mediated pathway. The results suggest M3R internalization as a potential
      mechanism to explain the exocrinopathy seen in pSS patients.

PMID- 22137888
TI  - Corticosterone synthesis inhibitor metyrapone ameliorates chronic hypobaric
      hypoxia induced memory impairment in rat.
AB  - Chronic exposure to hypobaric hypoxia causes oxidative stress and
      neurodegeneration leading to memory impairment. The present study aimed at
      investigating the role of corticosterone in hypoxia induced neurodegeneration and
      effect of metyrapone, a corticosterone synthesis inhibitor that reduces the
      stress induced elevation of corticosterone without affecting the basal level, in
      ameliorating chronic hypobaric hypoxia induced cognitive decline. Rats were
      exposed to simulated altitude of 25,000 ft for 0, 3, 7, 14 and 21 days to
      determine the temporal alterations in corticosterone and its receptors following
      exposure to hypobaric hypoxia. Our results showed an elevation of corticosterone
      in plasma and hippocampal tissue following 7 days of exposure, which declined on
      prolonged hypoxic exposure for 21 days. A concomitant increase in ROS and lipid
      peroxidation was observed along with depletion of intracellular antioxidants.
      Glucocorticoid and mineralocorticoid receptors were upregulated on 3 and 7 days
      of hypoxic exposure. Though expression of Glut1 and Glut3 were upregulated on 3
      days of hypoxic exposure, sharp decline in Glut1 expression following 7 days of
      hypoxic exposure leads to reduced neuronal glucose uptake. Administration of
      metyrapone from 3rd to 7th day of hypoxic exposure to suppress hypoxia induced
      increase in corticosterone levels resulted in reduced oxidative damage,
      neurodegeneration and improvement of intracellular energy status. The metyrapone
      treated hypoxic animals performed better in the Morris Water Maze. Further,
      administration of exogenous corticosterone along with metyrapone during hypoxic
      exposure blunted the neuroprotective effect of metyrapone indicating a role for
      corticosterone in mediating hypobaric hypoxia induced neurodegeneration and
      memory impairment.

PMID- 22137889
TI  - Inhibition of 5-lipoxygenase by U73122 is due to covalent binding to cysteine
      416.
AB  - U73122 which was originally identified as a phospholipase C inhibitor represents
      a potent direct inhibitor of purified 5-lipoxygenase (5-LO) with an IC50 value of
      30 nM. 5-LO catalyzes the conversion of arachidonic acid (AA) into leukotrienes
      which represent mediators involved in inflammatory and allergic reactions and in
      host defense reactions against microorganisms. Since the efficient inhibition of
      the human 5-LO enzyme depended on the thiol reactivity of the maleinimide group
      of U73122, we used this property to identify cysteine residues in the 5-LO
      protein that are important for 5-LO inhibition by U73122. We found by MALDI-MS
      that U73122 covalently binds to cysteine residues 99, 159, 248, 264, 416 and 449.
      Mutation of Cys416 to serine strongly reduces inhibition of 5-LO by U73122 and
      the additional mutation of three cysteines close to Cys416 further impairs 5-LO
      inhibition by the compound. Wash out experiments with U73122 and 5-LO indicated
      an irreversible binding of U73122. Together, our data suggest that the area
      around Cys416 which is close to the proposed AA entry channel to the active site
      is an interesting target for the development of new 5-LO inhibitors.

PMID- 22137890
TI  - Y-chromosomal STR analysis in the Pashtun population of Southern Afghanistan.
AB  - Afghanistan is a landlocked country in the heart of Asia and since the dawn of
      humankind Afghanistan has faced centuries of turmoil, strife, conflict, warfare,
      distress, social unrest, difficult climate, harsh terrain and due to its unique
      geostrategic position in Eurasia which has historically attracted commerce and
      conflict. It is an important stop along the Silk Road, connecting the far eastern
      civilizations to the western world. A 5000-year history of constant invasion.
      Afghanistan has been repeatedly invaded and conquered by rulers and super powers,
      neighboring interference in this conflict-tattered land for centuries yet rarely
      leading to the conquest of this rugged and challenging terrain nation. Afghans
      are not only shepherds, farmers and nomads but also intense fighters and fierce
      warriors. Currently very limited genetic studies have been performed in Afghan
      populations. 17 Y chromosomal short tandem repeats (Y-STRs) were analyzed in 125
      unrelated Pashtun (in hindi: Pathan) males residing in the Kandahar region of
      Southern Afghanistan. A total of 92 unique haplotypes were observed. The
      predominant haplotype reached a frequency of 9.6%. The haplotype diversity was
      0.987 and the discrimination capacity 73.6%. Analysis of molecular variance
      (AMOVA) reveals a considerable regional stratification within the country as well
      as between different Pashtun (Pathan) groups from Afghanistan, Pakistan and
      India.

PMID- 22137892
TI  - Identification of respiratory chain gene mutations that shorten replicative life
      span in yeast.
AB  - Aging is the progressive accumulation of alterations in cells that elevates the
      risk of death. The mitochondrial theory of aging postulates that free radicals
      produced by the mitochondrial respiratory system contribute to the aging process.
      However, the roles of individual electron transfer chain (ETC) components in
      cellular aging have not been elucidated. In this study, we analyzed the
      replicative life span of 73 yeast deletion mutants lacking the genes of the
      mitochondrial electron transfer chain system, and found that nine of these
      mutants (Deltande1, Deltatcm62, Deltarip1, Deltacyt1, Deltaqrc8, Deltapet117,
      Deltacox11, Deltaatp11, Deltafmc1) had significantly shorter life spans. These
      mutants had lower rates of respiration and were slightly sensitive to exogenous
      administration of hydrogen peroxide. However, only two of them, Deltande1 and
      Deltafmc1, produced higher amounts of intrinsic superoxide radicals in the
      presence of glucose compared to that of wild type cells. Interestingly, there
      were no significant alterations in the mitochondrial membrane potentials of these
      mutants. We speculate that the shorter life spans of ETC mutants result from
      multiple mechanisms including the low respiration rate and low energy production
      rather than just a ROS-dependent path.

PMID- 22137891
TI  - Gender differences in autoimmunity associated with exposure to environmental
      factors.
AB  - Autoimmunity is thought to result from a combination of genetics, environmental
      triggers, and stochastic events. Gender is also a significant risk factor with
      many diseases exhibiting a female bias. Although the role of environmental
      triggers, especially medications, in eliciting autoimmunity is well established
      less is known about the interplay between gender, the environment and
      autoimmunity. This review examines the contribution of gender in autoimmunity
      induced by selected chemical, physical and biological agents in humans and animal
      models. Epidemiological studies reveal that environmental factors can be
      associated with a gender bias in human autoimmunity. However many studies show
      that the increased risk of autoimmunity is often influenced by occupational
      exposure or other gender biased activities. Animal studies, although often
      prejudiced by the exclusive use of female animals, reveal that gender bias can be
      strain specific suggesting an interaction between sex chromosome complement and
      background genes. This observation has important implications because it argues
      that within a gender biased disease there may be individuals in which gender does
      not contribute to autoimmunity. Exposure to environmental factors, which
      encompasses everything around us, adds an additional layer of complexity.
      Understanding how the environment influences the relationship between sex
      chromosome complement and innate and adaptive immune responses will be essential
      in determining the role of gender in environmentally-induced autoimmunity.

PMID- 22137894
TI  - Crystal structure of human mitochondrial PheRS complexed with tRNA(Phe) in the
      active "open" state.
AB  - Monomeric human mitochondrial phenylalanyl-tRNA synthetase (PheRS), or hmPheRS,
      is the smallest known enzyme exhibiting aminoacylation activity. HmPheRS consists
      of only two structural domains and differs markedly from heterodimeric eukaryotic
      cytosolic and bacterial analogs both in the domain organization and in the mode
      of tRNA binding. Here, we describe the first crystal structure of mitochondrial
      aminoacyl-tRNA synthetase (aaRS) complexed with tRNA at a resolution of 3.0 A.
      Unlike bacterial PheRSs, the hmPheRS recognizes C74, the G1-C72 base pair, and
      the "discriminator" base A73, proposed to contribute to tRNA(Phe) identity in the
      yeast mitochondrial enzyme. An interaction of the tRNA acceptor stem with the
      signature motif 2 residues of hmPheRS is of critical importance for the
      stabilization of the CCA-extended conformation and its correct placement in the
      synthetic site of the enzyme. The crystal structure of hmPheRS-tRNA(Phe) provides
      direct evidence that the formation of the complex with tRNA requires a
      significant rearrangement of the anticodon-binding domain from the "closed" to
      the productive "open" state. Global repositioning of the domain is tRNA modulated
      and governed by long-range electrostatic interactions.

PMID- 22137893
TI  - Hydroxynonenal-generated crosslinking fluorophore accumulation in Alzheimer
      disease reveals a dichotomy of protein turnover.
AB  - Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal
      (HNE), which covalently bind amino acid residue side chains leading to protein
      inactivation and insolubility. Specific adducts of lipid peroxidation have been
      demonstrated in intimate association with the pathological lesions of Alzheimer
      disease (AD), suggesting that oxidative stress is a major component of AD
      pathogenesis. Some HNE-protein products result in protein crosslinking through a
      fluorescent compound similar to lipofuscin, linking lipid peroxidation and the
      lipofuscin accumulation that commonly occurs in post-mitotic cells such as
      neurons. In this study, brain tissue from AD and control patients was examined by
      immunocytochemistry and immunoelectron microscopy for evidence of HNE
      crosslinking modifications of the type that should accumulate in the lipofuscin
      pathway. Strong labeling of granulovacuolar degeneration (GVD) and Hirano bodies
      was noted but lipofuscin did not contain this specific HNE-fluorophore. These
      findings directly implicate lipid crosslinking peroxidation products as
      accumulating not in the lesions or the lipofuscin pathways, but instead in a
      distinct pathway, GVD, that accumulates cytosolic proteins.

PMID- 22137895
TI  - Crystal structures of mutant IspH proteins reveal a rotation of the substrate's
      hydroxymethyl group during catalysis.
AB  - Isoprenoids derive from two universal precursors, isopentenyl diphosphate and
      dimethylallyl diphosphate, which in most human pathogens are synthesized in the
      deoxyxylulose phosphate pathway. The last step of this pathway is the conversion
      of (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate into a mixture of isopentenyl
      diphosphate and dimethylallyl diphosphate catalyzed by the iron-sulfur protein
      IspH. The crystal structures reported here of the IspH mutant proteins T167C,
      E126D and E126Q reveal an alternative substrate conformation compared to the wild
      type structure. Thus, the previously observed alkoxide complex decomposes, and
      the substrate's hydroxymethyl group rotates to interact with Glu126. The carboxyl
      group of Glu126 then donates a proton to the hydroxyl group to enable water
      elimination. The structural and functional studies provide further knowledge of
      the IspH reaction mechanism, which opens up new routes to inhibitor design
      against malaria and tuberculosis.

PMID- 22137896
TI  - Facilitated assembly of the preinitiation complex by separated tail and
      head/middle modules of the mediator.
AB  - Mediator is a general coactivator of RNA polymerase II (RNA pol II) bridging
      enhancer-bound transcriptional factors with RNA pol II. Mediator is organized in
      three distinct subcomplexes: head, middle, and tail modules. The head and middle
      modules interact with RNA pol II, and the tail module interacts with
      transcriptional activators. Deletion of one of the tail subunits SIN4 results in
      derepression of a subset of genes, including FLR1, by a largely unknown
      mechanism. Here we show that derepression of FLR1 transcription in sin4Delta
      cells occurs by enhanced recruitment of the mediator as well as Swi/Snf and SAGA
      complexes. The tail and head/middle modules of the mediator behave as separate
      complexes at the induced FLR1 promoter. While the tail module remains anchored to
      the promoter, the head/middle modules are also found in the coding region. The
      separation of the tail and head/middle modules in sin4Delta cells is also
      supported by the altered stoichiometry of the tail and head/middle modules at
      several tested promoters. Deletion of another subunit of the tail module MED2 in
      sin4Delta cells results in significantly decreased transcription of FLR1,
      pointing to the importance of the integrity of the separated tail module in
      derepression. All tested genes exhibited increased recruitment of the tail
      domain; however, only genes with increased occupancy of the head/middle modules
      also displayed increased transcription. The separated tail module thus represents
      a promiscuous transcriptional factor that binds to many different promoters and
      is necessary for derepression of FLR1 in sin4Delta cells.

PMID- 22137897
TI  - The H2A-H2B dimeric kinetic intermediate is stabilized by widespread hydrophobic
      burial with few fully native interactions.
AB  - The H2A-H2B histone heterodimer folds via monomeric and dimeric kinetic
      intermediates. Within ~5 ms, the H2A and H2B polypeptides associate in a nearly
      diffusion limited reaction to form a dimeric ensemble, denoted I2 and I2*, the
      latter being a subpopulation characterized by a higher content of nonnative
      structure (NNS). The I2 ensemble folds to the native heterodimer, N2, through an
      observable, first-order kinetic phase. To determine the regions of structure in
      the I2 ensemble, we characterized 26 Ala mutants of buried hydrophobic residues,
      spanning the three helices of the canonical histone folds of H2A and H2B and the
      H2B C-terminal helix. All but one targeted residue contributed significantly to
      the stability of I2, the transition state and N2; however, only residues in the
      hydrophobic core of the dimer interface perturbed the I2* population.
      Destabilization of I2* correlated with slower folding rates, implying that NNS is
      not a kinetic trap but rather accelerates folding. The pattern of Phi values
      indicated that residues forming intramolecular interactions in the peripheral
      helices contributed similar stability to I2 and N2, but residues involved in
      intermolecular interactions in the hydrophobic core are only partially folded in
      I2. These findings suggest a dimerize-then-rearrange model. Residues throughout
      the histone fold contribute to the stability of I2, but after the rapid
      dimerization reaction, the hydrophobic core of the dimer interface has few fully
      native interactions. In the transition state leading to N2, more native-like
      interactions are developed and nonnative interactions are rearranged.

PMID- 22137898
TI  - Metabolic effects of silibinin in the rat liver.
AB  - The flavonolignan silibinin, which is a mixture of two diastereoisomers, silybin
      A and silybin B, is a component of the extract obtained from the fruit and seeds
      of the variegated milk thistle (Silybum marianum (L.) Gaertn. (Asteraceae)),
      known as silymarin. Among the therapeutic properties credited to silibinin, its
      antihyperglycaemic action has been extensively explored. Silibinin is
      structurally related to the flavonoids quercetin and fisetin, which have been
      previously demonstrated to be very active on liver metabolic processes related to
      glycaemic regulation. The aim of the present work was to investigate the effects
      of silibinin on metabolic pathways responsible for the maintenance of glycaemia,
      particularly glycogenolysis and gluconeogenesis, in the perfused rat liver. The
      activities of some key enzymes in these pathways and on parameters of energy
      metabolism in isolated mitochondria were also examined. At a concentration range
      of 50-300MUM, silibinin inhibited gluconeogenesis in the fasted condition and
      inhibited glycogenolysis and glycolysis in the fed condition. The mechanisms by
      which silibinin exerted these actions were multiple and complex. It inhibited the
      activity of glucose 6-phosphatase, inhibited the pyruvate carrier, and reduced
      the efficiency of mitochondrial energy transduction. It can also act by reducing
      the supply of NADH for gluconeogenesis and mitochondria through its pro-oxidative
      actions. In general, the effects and the potency of silibinin were similar to
      those of quercetin and fisetin. However, silibinin exerted some distinct effects
      such as the inhibitory effect on oxygen consumption in the fed condition and a
      change in the energy status of the perfused livers. It can be concluded that the
      effects of silibinin on liver glucose metabolism may explain its
      antihyperglycaemic property. However, this effect was, in part, secondary to
      impairment in cellular energy metabolism, a finding that should be considered in
      its therapeutic usage.

PMID- 22137899
TI  - The Austrian Tobacco Act in practice--analysing the effectiveness of partial
      smoking bans in Austrian restaurants and bars.
AB  - The purpose of this study is to examine the effectiveness of partial smoking bans
      in restaurants and bars, such as those currently in place in Austria, by
      evaluating adherence to the relevant regulations and assessing the satisfaction
      levels of those affected by these regulations. To evaluate adherence, 127
      randomly selected restaurants and bars were observed using a form of structured
      observation. In order to evaluate their level of satisfaction with the
      regulations, 342 randomly selected customers and 29 restaurant owners were
      interviewed using standardized questionnaires. The customers widely adhered to
      the partial smoking bans, but many of them were dissatisfied with the fragmented
      Austrian solution. Most restaurant owners showed neither adherence to the
      relevant regulations nor satisfaction with the partial smoking bans. The present
      study reveals that partial bans on smoking are an ineffective solution. The
      presumed advantages of these regulations, such as still allowing smoking in
      restaurants provided a spatial separation of smoking and non-smoking areas is
      guaranteed, cannot be confirmed; adherence to the partial bans is rather
      inadequate, especially among restaurant owners, and the level of satisfaction
      with the Austrian solution is poor as well, not only among smoking and non
      smoking customers, but also restaurant owners.

PMID- 22137900
TI  - Identification of plasma-responsive outer membrane proteins and their vaccine
      potential in Edwardsiella tarda using proteomic approach.
AB  - We have used differential sub-proteomic methodologies to detect Edwardsiella
      tarda outer membrane (OM) protein expression regulation during interaction with
      fish and human plasma, which is the critical step of the bacterial invasion
      internal organs via blood circulation. Seven and nine OM proteins were
      differentially expressed in response to fish and human plasma stress,
      respectively. Six proteins, TolB2, ETAE_2935, ETAE_0245, EvpA, ETAE_2675 and
      OmpA, were the shared proteins with the similar changes between the two plasma
      treatments. Except for EvpA, which was a known protein involved in bacterial
      pathogenesis and stress sensing, the others were first reported here to be
      related to bacterial invasion and infection. Out of them, four, upregulated
      ETAE_0245 and OmpA and downregulated ETAE_2675 and ETAE_2935, were selected for
      investigation of immune protection. The upregulated OmpA and ETAE_0245 were able
      to induce bactericidal antibodies in mice. These findings demonstrate that
      differential proteomic methodologies following protein expression regulation to
      interaction between host and pathogen with bacterial challenge post immunization
      of these altered proteins is a valid approach for identifying new vaccine
      candidates and nicely complements other high throughput mining strategies used
      for vaccine discovery.

PMID- 22137901
TI  - In vitro genotoxicity evaluation of 4-carboxyl-2,6
      dinitrophenylazohydroxynaphthalenes using human lymphocytes.
AB  - The genotoxicity of a new monoazo dye series, 4-carboxyl-2,6
      dinitrophenylazohydroxynaphthalenes has been evaluated using human lymphocytes by
      alkaline comet assay. Freshly isolated human lymphocytes were exposed to the dyes
      (AZ-01, -02, -03 and -04) at concentrations ranging from 0 to 500 MUM for 3h at
      37  degrees C. Appropriate negative (culture medium) and positive (100 MUM methyl
      methane sulfonate) controls were set up alongside with the dye-treated cells.
      Comet assay was performed to assess the extent of DNA damage. The four dyes gave
      varying results with respect to the parameters of DNA damage studied. AZ-01
      showed concentration-dependent DNA damage (% Tail DNA) while lower concentrations
      (31.25-62.5 MUM) did not produce any significant difference in the tail extent
      moment. AZ-02, the positional isomer of AZ-01, gave non-genotoxic effects at
      lower concentrations for the two DNA parameters. AZ-03 and AZ-04 (possessing
      additional C-7 substituents) did not produce significant genotoxic effect at all
      concentrations relative to the negative control. Two of these monoazo dyes show
      the potential of being used as edible colorants. The results revealed that
      genotoxicity of congeneric dyes bear a direct relationship to their chemical
      structure.

PMID- 22137902
TI  - Diallyl trisulfide suppresses the adipogenesis of 3T3-L1 preadipocytes through
      ERK activation.
AB  - Garlic and its organosulfur compounds display hypolipidemic effects by inhibiting
      fatty acid and cholesterol synthesis. We investigated the anti-adipogenic effect
      of diallyl trisulfide (DATS), the second most abundant organosulfide in garlic
      oil. We studied the effects of DATS in 3T3-L1 preadipocytes and the mechanism
      involved in its action. DATS (0-75 MUM) inhibited CCAAT/enhancer-binding protein
      (C/EBP) alpha and beta and peroxisome proliferator-activated receptor (PPAR)
      gamma mRNA and protein levels in a dose- and time-dependent manner, leading to a
      decrease of fatty acid synthase (FAS) expression and lipid accumulation in 3T3-L1
      cells. Insulin treatment induced a transient increase in ERK phosphorylation in
      3T3-L1 preadipocytes, and maximal induction was observed at 5 min and then
      declined. DATS, however, sustained ERK phosphorylation up to 120 min. In the
      presence of PD98059, the phosphorylation of ERK and suppression of PPARgamma
      expression and DNA binding activity of PPARgamma by DATS were reversed, and lipid
      accumulation was restored. In conclusion, these results indicate that DATS
      inhibits the differentiation of 3T3-L1 preadipocytes into adipocytes. DATS is
      likely to act by prolonging ERK activation, which leads to the down-regulation of
      adipogenic transcription factor expression during adipogenesis. Our results
      suggest that garlic may have potential as an anti-obesity agent.

PMID- 22137903
TI  - Triazine residues in raw milk and infant formulas from Spanish northwest, by a
      diphasic dialysis extraction.
AB  - Residue levels of herbicides (triazines) were determined in milk by a new and
      sensitive analytical method. A total of 312 samples were collected (70 infant
      formulas and 242 raw milk) biweekly during a 24-month period. A method is
      reported for the analysis of triazine with extraction by diphasic dialysis and
      determination by gas chromatography with nitrogen-phosphorus detection (CG/NPD)
      and by liquid chromatography/mass spectrometry (LC/MS) to confirm positive
      results. Detection limits (LODs) were 0.01 mg/l for terbuthylazine, 0.07 mg/l for
      simazine and 0.04 mg/l for atrazine by CG/NPD. Optimal extraction was obtained
      with dichloromethane at 34  degrees C, and stirring at 200 rpm for 4 h. This
      extraction method improves recovery by up to 89% for terbuthylazine, 75% for
      simazine and 116% for atrazine. The frequency of total samples containing
      triazine residues was 12.50%; considering, separately, raw milk and infant
      formulas, this percentage was 16.11% and 5.71%, respectively. Finally, because
      one sample contained triazine levels slightly higher than established MRLs and
      owing to the known effects of these contaminants on infants health and
      development, urgent actions are needed for monitoring and controlling of the
      level of contamination in infant formula which not exceeds tolerable limit
      recommended by European and Spanish legislation.

PMID- 22137904
TI  - Evaluation of the genotoxicity of the food additive, gum ghatti.
AB  - Gum ghatti is a food additive in some parts of the world, serving as an
      emulsifier, a stabilizer, and a thickening agent. To evaluate its genotoxic
      potential, we conducted Good Laboratory Practice compliant in vitro and in vivo
      studies in accordance with the Organisation for Economic Co-operation and
      Development (OECD) guidelines. No evidence of toxicity or mutagenicity was
      detected in a bacterial reverse mutation assay using five tester strains
      evaluating gum ghatti at up to 6 mg/plate, with or without metabolic activation.
      Gum ghatti also did not induce chromosome structural damage in a chromosome
      aberration assay using Chinese hamster ovary cells. To assess the ability to
      induce DNA damage in rodents, a combined micronucleus/Comet assay was conducted
      in male B6C3F1 mice. Gum ghatti was administered at 1000, 1500, and 2000
      mg/kg/day by gavage once daily for 4 days and samples were collected 4h after the
      final dosing. No effect of gum ghatti was measured on micronucleated reticulocyte
      (MN-RET) frequency in peripheral blood, or DNA damage in blood leukocytes or
      liver as assessed by the Comet assay. Our results show no evidence of genotoxic
      potential of gum ghatti administered up to the maximum concentrations recommended
      by OECD guidelines.

PMID- 22137905
TI  - Mangiferin glucuronidation: important hepatic modulation of antioxidant activity.
AB  - Mangiferin displays an extensive spectrum of pharmacological properties,
      including antioxidant activity. Its phase II metabolism in the presence of
      Aroclor 1254-induced and un-induced microsomal and cytosolic fractions from rat
      liver and the antioxidant potency of the glucuronidated conjugates were
      investigated. Mangiferin was not a substrate for the cytosolic
      sulphotransferases. Glucuronidation led to the formation of two
      monoglucuronidated metabolites of mangiferin and a monoglucuronidated metabolite
      of homomangiferin (a minor constituent of the mangiferin standard). Deconjugation
      utilising glucuronidase resulted in the disappearance of the metabolites, with
      the concomitant formation of the two parent compounds. Considering steric
      hinderance caused by the C-2 glucosyl moiety and the relative acidity of the
      xanthone OH groups, the 6-OH of mangiferin and, to a lesser degree the 7-OH, are
      likely to be the primary glucuronidation targets. The ferric iron reducing
      ability of the glucuronidated reaction mixture was reduced, while the free
      radical scavenging abilities of mangiferin, utilising on-line post-column HPLC
      DAD-DPPH. and HPLC-DAD-ABTS.+ assays, were eliminated, providing further evidence
      that the catechol arrangement at C-6 and C-7 was the preferred site of
      conjugation. This paper provides the first evidence that the glucuronidated
      metabolites of mangiferin resulted in a loss in free radical scavenging and
      ferric iron reducing ability.

PMID- 22137906
TI  - Surgical tick removal.

PMID- 22137907
TI  - Effects of elevated circulating cortisol levels on hydromineral status and gill
      tight junction protein abundance in the stenohaline goldfish.
AB  - A role for cortisol in the regulation of hydromineral balance and gill tight
      junction (TJ) protein transcript abundance in the stenohaline freshwater goldfish
      was investigated. Intraperitoneal cortisol implants (50, 100, 200, 400 MUg
      cortisol/g body weight) were used to dose-dependently elevate circulating
      cortisol levels over a 4 day period. Elevated cortisol did not significantly
      alter serum osmolality, serum Na(+) or muscle water content, however serum
      glucose and gill Na(+)-K(+)-ATPase activity were significantly increased and
      serum Cl(-) levels were significantly reduced when compared to control groups.
      Transcript levels for glucocorticoid receptor 1 (GR1) and mineralocorticoid
      receptor (MR) in the gill remained unchanged by cortisol treatment, however
      glucocorticoid receptor 2 (GR2) mRNA abundance was significantly down-regulated.
      Conversely, cortisol treatment significantly increased transcript and protein
      abundance of the TJ protein occludin in goldfish gill tissue, as well as mRNA
      abundance for claudin e, 7 and 8d. Goldfish tissue expression profiles
      demonstrated that transcripts encoding for these claudins are particularly
      abundant in the gill. Overall, results suggest a 'tightened' gill epithelium in
      response to elevated cortisol levels in goldfish. However, negative
      autoregulation of gill GR2 transcript suggests a lessened capacity to respond to
      cortisol and thus a potentially 'dampened' corticosteroid-mediated effect in the
      gill. Reduced systemic Cl(-) levels also suggest that sustained cortisol
      elevation in goldfish may have a detrimental effect on other ionoregulatory
      tissues.

PMID- 22137908
TI  - Individual variation and repeatability in urinary corticosterone metabolite
      responses to capture in the cane toad (Rhinella marina).
AB  - Urinary corticosterone metabolite enzyme-immunoassay (EIA) can be used for the
      non-invasive assessment of baseline levels and corticosterone responses in
      amphibians. In this study, urinary corticosterone responses of wild male cane
      toads (Rhinella marina) to confinement and repeated handling were measured to
      quantify individual variation in corticosterone responses for the first time in
      an amphibian species. Urine samples were collected at 0 h in the wild, hourly
      from 2 to 8 h after transfer into captivity, and again at 12 and 24 h in
      captivity. Toads were then held in captivity and subjected to the same sampling
      protocol on three occasions at 14 days intervals to quantify variation in
      corticosterone metabolite responses within and between toads. Baseline and
      individual corticosterone metabolite responses in male cane toads were generally
      consistent, with high statistical repeatabilities for 0 h (r=0.630), 6 h
      (r=0.793), 12 h (r=0.652) and 24 h (r=0.721) corticosterone metabolite
      concentrations, and for the total and corrected integrated corticosterone
      responses (r=0.567, p=0.033; r=0.728, p=0.014 respectively). Urinary
      corticosterone responses appear to be a stable, repeatable trait within
      individuals. Corticosterone responses in amphibians can be more readily measured
      when urine rather than plasma samples are collected, and the protocol established
      in the current study can now be applied to the study of variation in
      corticosterone responses in other amphibians.

PMID- 22137909
TI  - Farnesoic acid and methyl farnesoate production during lobster reproduction:
      possible functional correlation with retinoid X receptor expression.
AB  - Farnesoic acid (FA) and methyl farnesoate (MF) are juvenile hormone-related
      compounds secreted by the mandibular organ (MO) of crustaceans and play an
      important role in stimulation of ovarian maturation. To better understand how the
      MO activity influences female reproduction by secretion of FA and MF, the
      biosynthesis and release of these two compounds were measured in vitro by the
      incorporation of l-[(3)H-methyl]methionine into MF and [2-(14)C]acetate into FA
      by the MO of Homarus americanus. The production of FA is 7.5 times that of MF,
      and most FA and MF synthesized remained within the gland, and was not released
      into the surrounding medium. Most FA and MF were synthesized in the anterior fan
      fold region of the MO. The rates of biosynthesis of FA and MF were stage-related,
      with maximal production occurring during secondary vitellogenesis (i.e. stages 4
      and 5). A potential juvenoid receptor, retinoid X receptor (RXR), HaRXR, was
      characterized using PCR cloning techniques. HaRXR belongs to the nuclear hormone
      receptor superfamily and its deduced amino acid sequence shares a high homology
      to other RXRs of crustaceans, insects, and vertebrates. Transcripts of HaRXR can
      be detected in many tissues, and significant high expression level was detected
      in the MO, especially in the anterior fan-fold region. Expression of HaRXR was
      also related to reproductive stage, and maximal level of expression was observed
      at stage 4, in which secondary vitellogenesis is occurring. Changes in transcript
      level of HaRXR and the rates of FA/MF biosynthesis in the female reproductive
      cycle indicate that HaRXR and FA/MF may play important roles in crustacean
      reproduction.

PMID- 22137910
TI  - Variation in brain arginine vasotocin (AVT) and isotocin (IT) levels with
      reproductive stage and social status in males of three-spined stickleback
      (Gasterosteus aculeatus).
AB  - Arginine vasotocin (AVT) and isotocin (IT) are fish nonapeptides synthesized in
      separate hypothalamic neurons from where they are transported to the
      neurohypophysis for storage and release into circulation. AVT is known to
      modulate aggression, courtship and parental care or social communication in many
      species, including fish, amphibians and birds. In this paper we examined a link
      between the level of AVT and IT in the brain and particular reproductive behavior
      in males of three-spined stickleback (Gasterosteus aculeatus). AVT and IT levels
      in whole brain of males of three-spined stickleback vary depending on specific
      breeding behavior of the individuals and their social status. These studies have
      shown the highest AVT levels in aggressive males that took care of the eggs.
      Brain AVT concentrations are also increased in nuptial colored subordinate males
      that fight to change their social status. On the other hand, IT is significantly
      higher in aggressive dominant males that defend their territory. IT may be also
      involved in courtship in three-spined stickleback. These findings highlight the
      importance of determination of "free", bioavailable neuropeptides' level in
      behavioral studies.

PMID- 22137911
TI  - Differential physiological and endocrine responses of rainbow trout, Oncorhynchus
      mykiss, transferred from fresh water to ion-poor or salt water.
AB  - To understand the physiological and molecular endocrine changes that occur in
      response to a salinity challenge, we transferred rainbow trout from fresh water
      to an ion-poor or 240/00 saltwater treatment for 14 days. An increase in gill
      Na(+), K(+)-ATPase (NKA) activity in salt water was associated with higher mRNA
      expression for the NKA alpha1b subunit. In contrast, there was little change in
      gill NKA activity following transfer to ion-poor water, but the mRNA expression
      of NKA alpha1a was significantly elevated. Endocrine signals were assessed by
      measuring plasma cortisol concentrations and by quantifying changes in mRNA
      extracted from the gill for glucocorticoid receptors 1 and 2 (GR1 and GR2),
      mineralocorticoid receptor (MR), growth hormone receptor (GHR1), and prolactin
      receptor (PrlR). Cortisol increased after transfer to ion-poor and salt water,
      but both GR and MR mRNA in the gill showed little change. PrlR mRNA was
      significantly higher when fish were transferred to the ion-poor water and GHR1
      mRNA was elevated during the saltwater challenge. This study demonstrated an
      increase in gill PrlR mRNA that parallels the changes in gill NKA alpha1a when
      rainbow trout were transferred to a lower salinity level. Furthermore, the
      increase in gill GHR1 mRNA supports the importance of GH for seawater acclimation
      as there is a corresponding increase in the expression of gill NKA alpha1b, the
      saltwater isoform. GH and Prl, therefore, may differentially determine the
      function of cortisol in both fresh- and saltwater ionoregulation.

PMID- 22137912
TI  - Comparative insights of the kisspeptin/kisspeptin receptor system: lessons from
      non-mammalian vertebrates.
AB  - Kisspeptins, the peptide products of the Kiss1 gene, were initially identified in
      mammals as ligands of the G protein-coupled receptor 54 (GPR54; also termed
      Kiss1R) with ability to suppress tumor metastasis. In late 2003, the
      indispensable role of kisspeptins in the control of reproductive function was
      disclosed by the seminal observations that humans and mice carrying inactivating
      mutations of GPR54 displayed hypogonadotropic hypogonadism. Since then, numerous
      experimental studies, conducted initially in several mammalian species, have
      substantiated the roles of kisspeptins as essential players in the physiologic
      regulation of key aspects of reproductive maturation and function, including the
      timing of puberty onset, the dynamic control of gonadotropin secretion via
      stimulation of GnRH neurons, the transmission of the negative and positive
      feedback effects of sex steroids, the metabolic regulation of fertility and the
      control of reproductive function by environmental (photoperiodic) cues. Notably,
      while studies about kisspeptins in non-mammals appeared initially to lag behind,
      significant efforts have been devoted recently to define the genomic organization
      and functional characteristics of kiss/kisspeptins and gpr54 in different non
      mammalian species, including fish, reptiles and amphibians. These analyses, which
      will be comprehensively revised herein, have not only substantiated the
      conserved, essential roles of kisspeptins in the control of reproduction, but
      have also disclosed intriguing evolutionary aspects of kisspeptins and their
      receptors. Such comparative approaches will be instrumental to fuel further
      studies on the molecular regulation and physiological roles of kisspeptins, thus
      helping to unveil the complex biology of this system as indispensable regulator
      of the reproductive axis in a wide diversity of animal species.

PMID- 22137913
TI  - Methods for long-term 17beta-estradiol administration to mice.
AB  - Rodent models constitute a cornerstone in the elucidation of the effects and
      biological mechanisms of 17beta-estradiol. However, a thorough assessment of the
      methods for long-term administration of 17beta-estradiol to mice is lacking. The
      fact that 17beta-estradiol has been demonstrated to exert different effects
      depending on dose emphasizes the need for validated administration regimens.
      Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17beta
      estradiol using one of the two commonly used subcutaneous methods; slow-release
      pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and
      silastic capsules (with/without convalescence period, silastic laboratory tubing,
      inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 MUg 17beta
      estradiol/mL sesame oil), or a novel peroral method (56 MUg 17beta
      estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were
      used as ovariectomized and intact controls. Serum samples were obtained weekly
      for five weeks and 17beta-estradiol concentrations were measured using
      radioimmunoassay. The peroral method resulted in steady concentrations within-
      except on one occasion--the physiological range and the silastic capsules
      produced predominantly physiological concentrations, although exceeding the range
      by maximum a factor three during the first three weeks. The 0.18 mg pellet
      yielded initial concentrations an order of magnitude higher than the
      physiological range, which then decreased drastically, and the 0.72 mg pellet
      produced between 18 and 40 times higher concentrations than the physiological
      range during the entire experiment. The peroral method and silastic capsules
      described in this article constitute reliable modes of administration of 17beta
      estradiol, superior to the widely used commercial pellets.

PMID- 22137914
TI  - ERBB receptor feedback inhibitor 1: identification and regulation by estrogen in
      chickens.
AB  - The ERBB receptor feedback inhibitor 1 (ERRFI1) is a scaffolding adaptor protein,
      that plays a pivotal role in the epidermal growth factor receptor (EGFR) cell
      signaling cascade as a negative regulator affecting many important physiological
      processes. It was recently reported that ERRFI1 is a critical regulator of the
      response of the endometrium to estrogen regulation of tissue homeostasis in mice.
      But, very little is known about ERRF11 and hormonal regulation of the ERRFI1 gene
      in chickens. Therefore, in the present study, ERRFI1 gene was cloned and its
      differential expression profile analyzed at different embryonic stages, in
      various adult organs, and in oviducts from estrogen-treated chickens. Chicken
      ERRFI1 has an open-reading frame of 2848 nucleotides that encode for a protein of
      465 amino acids that has considerable homology to mammalian ERRFI1 proteins (>62%
      identity). Importantly, ERRFI1 mRNA is abundantly distributed in various organs
      from chickens. We then determined that DES (diethylstilbestrol, a synthetic
      nonsteroidal estrogen) induced ERRFI1 mRNA and protein predominantly in luminal
      and glandular epithelial cells of the oviduct. Further, we determined whether
      microRNAs, specifically miR-200b, miR-429 and miR-1639, influence ERRFI1
      expression via its 3'UTR and found that it does not directly target the 3'UTR of
      ERRFI1 mRNA. Therefore, it is unlikely that post-transcriptional regulation
      influences ERRFI1 expression in the chicken oviduct. In conclusion, our results
      indicate that ERRFI1 is a novel estrogen-stimulated gene expressed in epithelial
      cells of the chicken oviduct that likely plays an important role in oviduct
      growth and differentiation during early development of the chicken.

PMID- 22137915
TI  - Origin and convergent evolution of exendin genes.
AB  - Exendins are secretin hormone-like peptides that are components of the toxins
      from two venomous lizards, Heloderma suspectum (Gila monster) and Heloderma
      horridium (Mexican bearded lizard). Exendins-1 and -2 are vasoactive intestinal
      peptide (VIP)-like, both in sequence and function, while exendins-3 and -4 are
      glucagon-like peptide-1 (GLP-1)-like. The evolutionary origin of these peptides,
      and the genes that encode them, has been unclear. Recently, genes orthologous to
      exendin have been identified in reptiles, birds and amphibians. Analysis of the
      orthologous sequences demonstrates that the Heloderma exendins diversified by
      gene duplication from a common exendin ancestor on the Heloderma lineage after
      divergence from other reptiles, including the anole lizard and Burmese python. In
      addition, the exendin toxin peptide sequences, but not their pro or signal
      peptides, have evolved very rapidly on the Heloderma lineage, likely as they
      adapted to their new function as toxins. Exendins-1 and -2 not only evolved
      rapidly but their sequences have evolved convergently upon that of VIP, resulting
      in a doubling of its identity with VIP, while exendins-3 and -4 have retained an
      ancestral property of being more GLP-1-like sequences. These results suggest that
      the ancestral role of exendin, which is potentially still retained in some
      species, had greater similarity with proglucagon-derived peptides or GIP.

PMID- 22137916
TI  - Rheumatoid arthritis in 2011: an editorial.

PMID- 22137917
TI  - Precipitating and perpetuating factors of rheumatoid arthritis immunopathology:
      linking the triad of genetic predisposition, environmental risk factors and
      autoimmunity to disease pathogenesis.
AB  - Rheumatoid arthritis (RA) is considered to occur when genetic and environmental
      factors interact to trigger immunopathological changes and consequently an
      inflammatory arthritis. Over the last few decades, epidemiological and genetic
      studies have identified a large number of risk factors for RA development, the
      most prominent of which comprise cigarette smoking and the shared epitope
      alleles. These risks appear to differ substantially between anti-cyclic
      citrullinated peptide (ACPA)-positive and ACPA-negative disease. In this article,
      we will summarise the risk factors for RA development that have currently been
      identified, outlining the specific gene-environment and gene-gene interactions
      that may occur to precipitate and perpetuate autoimmunity and RA. We will also
      focus on how this knowledge of risk factors for RA may be implemented in the
      future to identify individuals at a high risk of disease development in whom
      preventative strategies may be undertaken.

PMID- 22137918
TI  - Co-morbidities in established rheumatoid arthritis.
AB  - Co-morbid conditions are common in patients with rheumatoid arthritis (RA).
      Although the presence of co-morbid conditions can be assessed using standardised
      indexes such as the Charlson index, most clinicians prefer to simply record their
      presence. Some co-morbidities are causally associated with RA and many others are
      related to its treatment. Irrespective of their underlying pathogenesis, co
      morbidities increase disability and shorten life expectancy, thereby increasing
      both the impact and mortality of RA. Cardiac co-morbidities are the most crucial,
      because of their frequency and their negative impacts on health. Treatment of
      cardiac risk factors and reducing RA inflammation are both critical in reducing
      cardiac co-morbidities. Gastrointestinal and chest co-morbidities are both also
      common. They are often associated with drug treatment, including non-steroidal
      anti-inflammatory drug and disease-modifying drugs. Osteoporosis and its
      associated fracture risk are equally important and are often linked to long-term
      glucocorticoid treatment. The range of co-morbidities associated with RA is
      increasing with the recognition of new problems such as periodontal disease.
      Optimal medical care for RA should include an assessment of associated co
      morbidities and their appropriate management. This includes risk factor
      modification where possible. This approach is essential to improve quality of
      life and reduce RA mortality. An area of genuine concern is the impact of
      treatment on co-morbidities. A substantial proportion is iatrogenic. As
      immunosuppression with conventional disease-modifying drugs and biologics has
      many associated risks, ranging from liver disease to chest and other infections,
      it is essential to balance the risks of co-morbidities against the anticipated
      benefits of treatment.

PMID- 22137919
TI  - What is the outcome of RA in 2011 and can we predict it?
AB  - There are secular trends in improvement in disease activity and X-ray damage at
      baseline and cross-sectionally in prevalent cases of rheumatoid arthritis (RA) in
      recent years. These changes should translate into improved physical function and
      mortality, but evidence for this is lacking, perhaps because the mean age at RA
      diagnosis and of prevalent cases is increasing, mainly as a consequence of
      demographic changes. This trend is accompanied by an increasing prevalence of co
      morbidities, in particular cardiovascular and respiratory disease. The higher
      prevalence of smoking, diabetes and physical inactivity in RA cases contributes
      to the burden of co-morbidity. Predictors of poorer treatment response and thus a
      worse prognosis include female gender, being a smoker, autoantibody positivity,
      high baseline disease activity and co-morbidities such as depression. There is a
      need for better understanding of predictors of treatment response to guide the
      right choice of therapy and thus improve outcome further.

PMID- 22137920
TI  - Assessment of control of rheumatoid arthritis disease activity.
AB  - As very effective targeted biological therapies have become available to treat
      rheumatoid arthritis (RA), remission is now the goal of treatment. Since 1981,
      efforts have been undertaken to develop criteria for clinical remission in RA.
      Although several different measures of disease activity have been proposed, many
      issues remain unresolved. Active joint inflammation, even if involving only a few
      joints, negatively impacts a patient's quality of life and may ultimately result
      in structural damage. Thus, a low disease activity state (LDAS), which has been
      adopted as the target in clinical trials of 'treat to target', may not be the
      optimal treatment target in clinical practice. Similarly, the definitions of
      remission used in clinical trials may not be appropriate for use in daily
      clinical practice because some allow for the presence of several tender and
      swollen joints. Measures of disease activity do not necessarily correlate with
      structural remission, which implies halting progression of radiographic evidence
      of damage over time. Because no single measure of RA disease activity fully
      quantifies the global burden of disease, rheumatologists must follow multiple
      parameters to assess disease activity thoroughly and to adjust treatment
      optimally.

PMID- 22137921
TI  - Established rheumatoid arthritis: rationale for best practice: physicians'
      perspective of how to realise tight control in clinical practice.
AB  - Developments in the understanding of the pathogenesis of rheumatoid arthritis
      (RA) and the introduction of targeted biologic therapies have greatly advanced
      the management of RA in clinical practice. The management of RA is now aimed at
      achieving remission, to prevent joint damage and disability. In particular, a
      critical period early in disease is recognised, in which early aggressive
      treatment with disease-modifying therapy is advocated. Although a state of
      remission is the ideal, this chapter discusses the difficulties which may arise
      in achieving this goal in patients with established disease. The evidence for
      best management, aimed at achieving clinical remission in established disease, is
      reviewed. The consequences of incomplete control of chronic inflammation in
      established disease, including pain, disability and co-morbidities (such as
      cardiovascular disease and osteoporosis), also pose a significant clinical
      challenge. The rationale for a multidisciplinary team approach in reducing the
      associated morbidity and mortality of the disease are examined.

PMID- 22137922
TI  - The use of conventional disease-modifying anti-rheumatic drugs in established RA.
AB  - Conventional disease-modifying anti-rheumatic drugs (DMARDs) are the main tool to
      treat any form of rheumatoid arthritis (RA). Over the years, treatment strategies
      and use of DMARDs have changed. 'Tight control' and 'treat-to-target' are now the
      present paradigms. Combining DMARDs and adapting their dosages to obtain the best
      (clinical) result in individual RA patients with the least amount of medication
      has been and is studied worldwide. Literature results are mainly on early RA
      however, and they do not necessarily also apply to patients with established RA.
      Methotrexate (MTX) is the key conventional DMARD also for the treatment of
      established RA, and MTX often has to be combined with other DMARDs to reach low
      disease activity. However, there is lack of data on combination DMARD strategies
      and on how to treat best individual patients with established RA. In this review,
      we address these uncertainties and give an overview of available data.

PMID- 22137923
TI  - B-cell therapies in established rheumatoid arthritis.
AB  - B-cell depletion therapy based on rituximab is effective and relatively safe in
      established rheumatoid arthritis. Rituximab is licensed for the treatment of
      rheumatoid arthritis in combination with methotrexate and in patients who did not
      respond or cannot tolerate tumour necrosis factor antagonists. Sustained control
      of disease activity can be achieved by repeated courses of treatment. The optimal
      dose and schedule of retreatment are still not established. Nevertheless, data
      are now available that provide a good base for current clinical practice and a
      good starting point for further research. In general, rituximab has a good safety
      profile with most studies showing similar incidences of serious adverse events
      and infections to placebo. However, reasonable and well-funded doubts remain over
      the safety of long-term strategies of treatment of rheumatoid arthritis with
      rituximab, in particular, in relation to the risk of secondary
      hypogammaglobulinaemia and potential increased risk of infections.

PMID- 22137924
TI  - Anti-TNF therapy.
AB  - There are now five anti-tumour necrosis factor (TNF) drugs licenced for use in
      rheumatoid arthritis. This chapter examines the similarities and differences
      between the drugs and looks for clues with regard to their rational prescribing.
      The major difference is between the monoclonal antibody-based drugs and the
      soluble receptor etanercept. Etanercept exhibits the best drug survival and is
      also associated with a lower risk of opportunistic infections, particularly
      tuberculosis. Immunogenicity should explain some of the differences between the
      different drugs but the lack of standardised assays has hindered this area of
      research. The optimal approach to the patient who has failed their first anti-TNF
      remains unclear and awaits appropriate clinical trials. The safety profile of
      anti-TNFs has become clearer, largely through registry data. There is a small
      increase in serious and opportunistic infections but there does not appear to be
      a heightened cancer risk, and cardiovascular risk is probably reduced.

PMID- 22137925
TI  - Imaging in rheumatoid arthritis.
AB  - The optimal management of rheumatoid arthritis (RA) requires tools that allow
      early and accurate disease diagnosis, prediction of poor prognosis and responsive
      monitoring of therapeutic outcomes. Conventional radiography has been widely used
      in both clinical and research settings to assess RA joint damage due to its
      feasibility, but it has limitations in early disease detection and difficulty
      distinguishing between active treatments in modern trials. Imaging modalities
      such as magnetic resonance imaging (MRI) and ultrasound (US) have the advantage
      of detecting both joint inflammation and damage and hence they can provide
      additional and unique information. This can be especially useful in the context
      of early and/or undifferentiated joint disease when detection of soft tissue and
      bone marrow abnormalities is desirable. This review focusses on the recent
      literature concerning modern imaging, and provides clinicians with an insight
      into the role of imaging in modern RA diagnosis, prognosis and monitoring.

PMID- 22137926
TI  - Quality of life and the outcome of established rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a long-term condition causing joint pain and
      swelling and sometimes systemic involvement. The aims of treatment are, first, to
      reduce the impact the disease has on a patient and, second, to halt progression
      of disease. The advent of intensive therapy, including biologics, has led to a
      major improvement in outcome. To assess treatment impact, formal outcome measures
      have been developed. Traditionally, these focussed on the clinical aspects such
      as disease activity and joint damage. More recently, there has been an increased
      focus on patient-related outcome measures including quality-of-life measures.
      These enable illness evaluation from patients' perspectives, examination of care
      quality and comparison of the effectiveness and cost-effectiveness of treatment.
      This article examines advantages and disadvantages of the various outcome
      measures which are generally used in RA, with a focus on quality of life and
      patient-related measures.

PMID- 22137927
TI  - Economic consequences and potential benefits.
AB  - Patients with established rheumatoid arthritis (RA) may incur important resource
      utilisation and work productivity loss, resulting in high costs of illness.
      Impairment in physical function, which increases with disease duration, is the
      main variable driving all aspects of these costs. The large variation of costs
      across administrations is a complex issue and results not only from differences
      in access to and provision of care but also from absolute differences in the
      prices for health-care or loss of paid work. Despite the major effects of
      biologicals on almost all aspects of health, the literature shows that in
      established RA, the cost-utility ratios are high when compared to adjusting or
      switching non-biological disease-modifying anti-rheumatic drugs (DMARD)
      sequences. Until the prices of the biologicals can be reduced, the challenge for
      optimising the use of biologicals in treatment sequences in RA is to improve
      selection of patients that would be unresponsive to non-biological DMARDs in an
      early phase of the disease and identification of patient groups in which
      biologicals can be successfully stopped.

PMID- 22137928
TI  - Tolerance induced by anti-DNA Ig peptide in (NZB*NZW)F1 lupus mice impinges on
      the resistance of effector T cells to suppression by regulatory T cells.
AB  - We have previously shown that immune tolerance induced by the anti-DNA Ig peptide
      pCons in (NZB*NZW)F(1) (NZB/W) lupus mice prolonged survival of treated animals
      and delayed the appearance of autoantibodies and glomerulonephritis. Part of the
      protection conferred by pCons could be ascribed to the induction of regulatory T
      cells (T(Reg)) that suppressed the production of anti-DNA antibodies in a p38
      MAPK-dependent fashion. Here we show that another effect of pCons in the
      induction of immune tolerance in NZB/W lupus mice is the facilitation of effector
      T cell suppression by T(Reg). These new findings indicate that pCons exerts
      protective effects in NZB/W lupus mice by differentially modulating the activity
      of different T cell subsets, implying new considerations in the design of T(Reg)
      based approaches to modulate T cell autoreactivity in SLE.

PMID- 22137929
TI  - Mutational analysis of VCP gene in familial amyotrophic lateral sclerosis.
AB  - Mutations in valosin-containing protein (VCP) gene, already known to be
      associated with the multisystemic disorder, inclusion body myopathy with Paget's
      disease and frontotemporal dementia (IBMPFD), have been recently found also in
      familial cases of amyotrophic lateral sclerosis (ALS). To further define the
      frequency of VCP mutations in ALS Italian population, we screened a cohort of 166
      familial ALS and 14 ALS-frontotemporal dementia (FTD) individuals. We identified
      a previously reported synonymous mutation (c.2093A>C; p.Q568Q), 2 intronic
      variants (c.1749-14C>T; c.2085-3C>T), and 1 nucleotide change (c.2814G>T) in the
      3' untranslated region (UTR). Bioinformatical analyses predicted no changes in
      splicing process or microRNA binding sites. Our results do not confirm a main
      contribution of VCP gene to familial ALS in the Italian population.

PMID- 22137930
TI  - Biochemical and transcriptional profiling to triage additional activities in a
      series of IGF-1R/IR inhibitors.
AB  - Therapeutic development of a targeted agent involves a series of decisions over
      additional activities that may be ignored, eliminated or pursued. This paper
      details the concurrent application of two methods that provide a spectrum of
      information about the biological activity of a compound: biochemical profiling on
      a large panel of kinase assays and transcriptional profiling of mRNA responses.
      Our mRNA profiling studies used a full dose range, identifying subsets of
      transcriptional responses with differing EC(50)s which may reflect distinct
      targets. Profiling data allowed prioritization for validation in xenograft
      models, generated testable hypotheses for active compounds, and informed
      decisions on the general utility of the series.

PMID- 22137931
TI  - Synthesis, anti-inflammatory activity and ulcerogenic liability of novel nitric
      oxide donating/chalcone hybrids.
AB  - A group of novel nitric oxide (NO) donating chalcone derivatives was prepared by
      binding various amino chalcones with different NO donating moieties including;
      nitrate ester, oximes and furoxans. Most of the prepared compounds showed
      significant anti-inflammatory activity using carrageenan-induced rat paw edema
      method compared with indomethacin. The prepared compounds exhibited more
      protection than indomethacin in regard to gastric toxicity. Histopathological
      investigation confirmed the beneficial effects of the NO releasing compounds in
      reducing ulcer formation. The incorporation of the NO-donating group into the
      parent chalcone derivatives caused a moderate increase in the anti-inflammatory
      activity with a marked decrease in gastric ulcerations compared to their parent
      chalcone derivatives.

PMID- 22137932
TI  - Design, synthesis and biological activity of sphingosine kinase 2 selective
      inhibitors.
AB  - Sphingosine kinase (SphK) has emerged as an attractive target for cancer
      therapeutics due to its role in cell survival. SphK phosphorylates sphingosine to
      form sphingosine 1-phosphate (S1P), which has been implicated in cancer growth
      and survival. SphK exists as two different isotypes, namely SphK1 and SphK2,
      which play different roles inside the cell. In this report, we describe SphK
      inhibitors based on the immunomodulatory drug, FTY720, which is phosphorylated by
      SphK2 to generate a S1P mimic. Structural modification of FTY720 provided a
      template for synthesizing new inhibitors. A diversity-oriented synthesis
      generated a library of SphK inhibitors with a novel scaffold and headgroup. We
      have discovered subtype selective inhibitors with K(i)'s in the low micromolar
      range. This is the first report describing quaternary ammonium salts as SphK
      inhibitors.

PMID- 22137933
TI  - Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting
      bromodomains of the BET family.
AB  - Benzodiazepines are psychoactive drugs with anxiolytic, sedative, skeletal muscle
      relaxant and amnestic properties. Recently triazolo-benzodiazepines have been
      also described as potent and highly selective protein interaction inhibitors of
      bromodomain and extra-terminal (BET) proteins, a family of transcriptional co
      regulators that play a key role in cancer cell survival and proliferation, but
      the requirements for high affinity interaction of this compound class with
      bromodomains has not been described. Here we provide insight into the structure
      activity relationship (SAR) and selectivity of this versatile scaffold. In
      addition, using high resolution crystal structures we compared the binding mode
      of a series of benzodiazepine (BzD) and related triazolo-benzotriazepines (BzT)
      derivatives including clinically approved drugs such as alprazolam and midazolam.
      Our analysis revealed the importance of the 1-methyl triazolo ring system for BET
      binding and suggests modifications for the development of further high affinity
      bromodomain inhibitors.

PMID- 22137934
TI  - Synthesis, biological evaluation and molecular modeling of 1,2,3-triazole analogs
      of combretastatin A-1.
AB  - The synthesis, cytotoxicity, inhibition of tubulin polymerization data and anti
      angiogenetic effects of seven 1,5-disubstituted 1,2,3-triazole analogs and two
      1,4-disubstituted 1,2,3-triazole analogs of combretastatin A-1 (1) are reported
      herein. The biological studies revealed that the 1,5-disubstituted 1,2,3
      triazoles 3-methoxy-6-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)benzene
      1,2-diol (6), 3-methoxy-6-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5
      yl)benzene-1,2-diamine (8) and 5-(2,3-difluoro-4-methoxyphenyl)-1-(3,4,5
      trimethoxyphenyl)-1H-1,2,3-triazole (9) were the three most active compounds
      regarding inhibition of both tubulin polymerization and angiogenesis. Molecular
      modeling studies revealed that combretastatins 1 and 2 and analogs 5-11 could be
      successfully docked into the colchicine binding site of alpha,beta-tubulin.

PMID- 22137935
TI  - Measurement of persistent organic pollutants (POPs) in plastic resin pellets from
      remote islands: toward establishment of background concentrations for
      International Pellet Watch.
AB  - Plastic resin pellets collected from remote islands in the Pacific, Atlantic, and
      Indian Oceans and the Caribbean Sea were analyzed for polychlorinated biphenyls
      (PCBs), dichloro-diphenyltrichloroethane and its degradation products (DDTs), and
      hexachlorocyclohexanes (HCHs). Concentrations of PCBs (sum of 13 congeners) in
      the pellets were 0.1-9.9 ng/g-pellet. These were 1-3 orders of magnitude smaller
      than those observed in pellets from industrialized coastal shores. Concentrations
      of DDTs in the pellets were 0.8-4.1 ng/g-pellet. HCH concentrations were 0.6-1.7
      ng/g-pellet, except for 19.3 ng/g-pellet on St. Helena, where current use of
      lindane is likely influence. This study provides background levels of POPs
      (PCBs<10 ng/g-pellet, DDTs <4 ng/g-pellet, HCHs <2 ng/g-pellet) for International
      Pellet Watch. Sporadic large concentrations of POPs were found in some pellet
      samples from remote islands and should be considered in future assessments of
      pollutants on plastic debris.

PMID- 22137936
TI  - Longevity of materials for pit and fissure sealing--results from a meta-analysis.
AB  - OBJECTIVE: This meta-analysis investigates the clinical retention of pit and
      fissure sealants in relation to observation time and material type. DATA, SOURCES
      AND STUDY SELECTION: A search in the MEDLINE, EMBASE and CENTRAL databases
      identified 2944 abstracts (published prior to 9/30/2011), of which 485 clinical
      publications were analyzed in detail. A total of 146 articles included
      information about sealant retention, with a minimum observation time of 2 years.
      These publications were analyzed to determine the retention rates of the various
      materials studied (UV-light-, light- and auto-polymerizing resin-based sealants,
      fluoride-releasing materials, compomers, flowable composites and glass-ionomer
      cement-based sealants). The meta-analysis used random effects models for
      longitudinal logistic regression and Bayesian statistics. RESULTS: As part of the
      systematic review, 98 clinical reports and 12 field trial reports were
      identified. Auto-polymerizing sealants had the longest observation time (up to 20
      years) and were found to have a 5-year retention rate of 64.7% (95%CI=57.1
      73.1%), which was estimated from the meta-analysis model. Resin-based light
      polymerizing sealants and fluoride-releasing products showed similar 5-year
      retention rates (83.8%, 95%CI=54.9-94.7% and 69.9%, 95%CI=51.5-86.5%,
      respectively) for completely retained sealants. In contrast to these high
      retention rates, poor retention rates were documented for UV-light-polymerizing
      materials, compomers and glass-ionomer-cement-based sealants (5-year retention
      rates were <19.3%). Retention rates for UV-light-polymerizing materials,
      compomers and glass-ionomer-cement-based sealants were classified as inferior.
      CONCLUSIONS VERSUS SIGNIFICANCE: The results of this meta-analysis suggested that
      resin-based sealants can be recommended for clinical use. The faster and less
      error-prone clinical application of light-polymerizing materials, however, makes
      them the preferred choice for daily dental practice.

PMID- 22137937
TI  - Nano-porous thermally sintered nano silica as novel fillers for dental
      composites.
AB  - OBJECTIVES: The study evaluates properties of an experimental dental composite
      consisting of a porous thermally sintered nano-silica as filler. The properties
      are compared with those of an experimental composite containing micro fillers and
      a commercially available nano-composite, Filtek Supreme((r)) Translucent.
      Different models are used to predict the elastic modulus and strength of the
      composites. METHODS: Nano-silica with primary particles of 12 nm was thermally
      sintered to form nanoporous filer particles. The experimental composites were
      prepared by incorporating 70 wt.% of the fillers into a mixture of Bis-GMA and
      TEGDMA as matrix phase. Having added photoinitiator system the composites were
      inserted into the test molds and light-cured. The microfiller containing
      composites were also prepared using micron size glass fillers. Degree of
      conversion (DC%) of the composites was measured using FTIR spectroscopy.
      Diametral tensile strength (DTS), flexural strength, flexural modulus and
      fracture toughness were measured. SEM was utilized to study the cross section of
      the fractured specimens. The surface topography of the specimens was investigated
      using atomic force microscopy (AFM). The specific surface area of the sintered
      nano silica was measured using BET method. The data were analyzed and compared by
      ANOVA and Tukey HSD tests (significance level=0.05). RESULTS: The results showed
      improvements in flexural modulus and fracture toughness of the composites
      containing sintered filler. AFM revealed a lower surface roughness for sintered
      silica containing composites. No significant difference was observed between DTS,
      DC%, and flexural strength of the sintered nanofiller composite and the Filtek
      Supreme((r)). The results also showed that the modulus of the composite with
      sintered filler was higher than the model prediction. SIGNIFICANCE: The thermally
      sintered nano-porous silica fillers significantly enhanced the mechanical
      properties of dental composites introducing a new approach to develop materials
      with improved properties.

PMID- 22137938
TI  - Geometry of imaginary spaces.
AB  - "Imaginary space" is a three-dimensional visual awareness that feels different
      from what you experience when you open your eyes in broad daylight. Imaginary
      spaces are experienced when you look "into" (as distinct from "at") a picture for
      instance. Empirical research suggests that imaginary spaces have a tight,
      coherent structure, that is very different from that of three-dimensional
      Euclidean space. This has to be due to some constraints on psychogenesis, that is
      the development of awareness. I focus on the topic of how, and where, the
      construction of such geometrical structures, that figure prominently in one's
      awareness, is implemented in the brain. My overall conclusion-with notable
      exceptions-is that present day science has no clue. I indicate some possibly
      rewarding directions of research.

PMID- 22137939
TI  - The effects of enteral ghrelin administration on the remodeling of the small
      intestinal mucosa in neonatal piglets.
AB  - Ghrelin is a multifunctional peptide produced predominantly in the stomach,
      however substantial amounts have also been found in colostrum and milk. The aim
      of the study was to investigate the effect of exogenous ghrelin, administered
      intra-gastrically, on the processes of mitosis, apoptosis, autophagy, crypt
      fission and changes in histometry of the small intestine mucosa in neonatal pigs,
      fed with a milk formula. Three groups (n=6) of piglets were used in the study.
      The pigs were fed either milk formula (C7) or milk formula together with ghrelin,
      administered via a stomach tube (7.5 MUg/kg body weight (BW), (LG)) and 15 MUg/kg
      BW (HG), every 8h for 6 days. Compared to the control group (C7), feeding milk
      formula supplemented with ghrelin resulted in significant changes in the small
      intestinal morphometry and mucosa histometry. The observed changes were dependent
      on the dosage of hormone and the part of intestine investigated. Administration
      of ghrelin via the stomach tube (HG) significantly influenced epithelial cell
      renewal. Moreover, we demonstrated that autophagy is involved in the small
      intestine mucosa remodeling and ghrelin may be an important factor for its
      regulation. In conclusion, we found that enteral ghrelin influences the gut
      mucosa remodeling in a dose-related manner in the early postnatal period.
      Moreover in neonates, stomach activity does not interfere with the action of
      ghrelin in the small intestine.

PMID- 22137941
TI  - Effect of oral contraceptive therapy on homocysteine and C-reactive protein
      levels in women: an observational study.
AB  - OBJECTIVE: Increased levels of homocysteine and C-reactive protein (CRP) are
      considered as independent risk factors for atherosclerosis. As the level of these
      factors is affected by sex hormones, a population-based assessment of their
      changes following oral contraceptive therapy is needed to avoid the side effects
      that might arise of these variations. To this aim, the present study was to
      investigate the effect of combined oral contraceptive (OCP) on CRP and
      homocysteine levels among young healthy women. METHODS: We conducted an
      observational cross-sectional analysis of 90 healthy, non-obese women (mean age
      25 years and body-mass index 22 kg/m2). Forty-five healthy women on OCP and 45
      healthy controls were studied for CRP and homocysteine levels by enzyme-linked
      immunosorbent assay (ELISA). Unpaired t test and Chi-square test were used for
      comparison of variables between oral contraceptive users and non-oral
      contraceptive users. RESULTS: The results showed that the homocysteine (13.268+/
      3.475 vs. 7.288+/-2.621 umol/L) and CRP (5863.0+/-1349.5 vs. 1138.3+/-691.12
      ng/ml) levels were significantly higher in women receiving OCP in comparison with
      the control group (p=0.027 and p<0.001, respectively). CONCLUSION: The alteration
      in homocysteine and CRP levels could be attributed to the OCP suggesting that use
      of these pills should be reviewed in women with increased risk of atherosclerosis
      and other cardiovascular risk factors.

PMID- 22137940
TI  - Morbidity and hospitalizations of adults with Down syndrome.
AB  - Over the last decade a significant increase in the life expectancy of people with
      Down syndrome (DS) has been observed, which has caused a higher incidence of
      morbidity as they age. However, there is a lack of literature regarding morbidity
      and hospitalization of adults with DS. Analysis of 297 hospitalizations of 120
      adults with DS aged 18-73 years hospitalized at Hadassah Medical Centers during
      the years 1988-2007 compared with data of the general population, hospitalized at
      the same period. At the age range 18-66 years, mean number of hospitalizations
      was significantly higher than the general population (P = 0.000001) with
      hospitalization also significantly longer (P = 0.0009). Exceptionally long
      hospitalizations were seen at the departments of internal medicine, dermatology
      and intensive care units. There was no significant difference in mortality
      between DS and the general population (P = 0.221). More than a fourth of the
      hospitalizations were caused by infectious diseases, mostly respiratory
      infections. Hypothyroidism was more prevalent compared with the estimated number
      reported by the literature (30.8% vs. 15%). Convulsive disorder was prevalent as
      well (15.8%). However, the prevalence of congenital heart disease, dementia,
      osteoporosis and obesity was found less than expected. Adults with DS are
      hospitalized more than the general population and for longer duration. The
      results of this study emphasize the need for preventive community-based medicine,
      awareness of co-morbidities and possible deterioration and to prepare the medical
      staff for a complex course of illness, expecting longer hospitalizations, arising
      from the complexity of this population.

PMID- 22137942
TI  - Diabetic cardiomyopathy.
AB  - Diabetic individuals are at significantly greater risk of developing heart
      failure (HF) independent from other risk factors such as coronary artery disease
      (CAD) and hypertension. Diabetic cardiomyopathy (DCP) is defined as ventricular
      dysfunction in the absence of hypertension, coronary artery and valvular heart
      disease, which increases the risk of HF.  Due to better understanding of its
      pathophysiology and clinical importance, DCP is more frequently recognized in
      daily practice. The most important mechanisms of DCP are hyperglycemia, insulin
      resistance/hyperinsulinemia, abnormal fatty acid metabolism, increased apoptosis,
      cardiac autonomic neuropathy and local renin-angiotensin-aldosterone system
      (RAAS) overactivation. Echocardiography is the most frequently used diagnostic
      method for the detection of this pathology. Currently, although there is no
      specific treatment for DCP, strict glycemic and concomitant risk factor controls
      seems to be the most important target strategy for prevention of the progression
      and treatment of DCP. In this article, we aim to provide an extensive review on
      the pathophysiology, diagnosis, management of DCP.

PMID- 22137943
TI  - Angiography findings after late bidirectional cavopulmonary shunt operation at
      mid-term follow-up.

PMID- 22137944
TI  - [Successful VT ablation in a patient with ventricular assist device and 
      implantable cardiac defibrillator].

PMID- 22137945
TI  - A mobile structure at the entrance of the left atrial appendage in a patient with
      malignant fibrous histiocytoma.

PMID- 22137947
TI  - Mitral valve surgery; from median sternotomy to closed chest procedures, from
      replacement to repair techniques/clinical outcomes of mitral valve repair in
      mitral regurgitation: a prospective analysis of 100 consecutive patients.

PMID- 22137946
TI  - Catecholamine-induced cardiomyopathy and paraganglioneuroma in a pediatric
      patient.

PMID- 22137948
TI  - E. coli outbreak and myocarditis: a story in cardiology.

PMID- 22137949
TI  - Electrocardiographic diagnostic dilemma: gradual QRS widening recorded by rhythm
      Holter monitoring.

PMID- 22137950
TI  - Acute left main coronary artery occlusion following TAVI and emergency solution.

PMID- 22137951
TI  - Emergency double-valve repair during acute aortic dissection type A operation.

PMID- 22137952
TI  - Diagnostic importance of aVR derivation in exercise stress testing for
      interpreting of multivessel and proximal LAD disease.

PMID- 22137953
TI  - "Broken heart" syndrome complicated by acute severe mitral regurgitation.

PMID- 22137954
TI  - Cerebral and coronary artery aneurysms in a patient with Behcet's disease.

PMID- 22137955
TI  - Transcatheter aortic valve implantation: a novel perspective by real-time three
      dimensional transesophageal echocardiography.

PMID- 22137956
TI  - Congenital aortic and pulmonary stenoses demonstrated by multislice computed
      tomography.

PMID- 22137957
TI  - Congenital giant aneurysm of the right atrium.

PMID- 22137958
TI  - [Abbas Vesim Efendi (date of death-1760)].

PMID- 22137960
TI  - Typical atrial flutter. What's new?

PMID- 22137961
TI  - [Management meeting of the Anatolian Journal of Cardiology, improvements, again
      our losses, new gains].

PMID- 22137962
TI  - Molecular cloning, characterization of copper/zinc superoxide dismutase and
      expression analysis of stress-responsive genes from Eisenia fetida against
      dietary zinc oxide.
AB  - The full length cDNA of copper/zinc superoxide dismutase (Cu/Zn-SOD) from Eisenia
      fetida (E. fetida) was cloned (GenBank accession no. JN579648). Sequence
      characterization revealed that the cDNA contained characteristic Cu/Zn-SOD family
      signatures ((45)GFHVHEFGDNT(55) and (138)GNAGGRLACGVI(149)), cysteines (Cys-58
      and-146) predicted to form one disulphide bond, Cu-binding (His-47, -49, -64 and 
      120) and Zn-binding (His-64, -72, -81 and Asp-84). They were essential for the
      structure and function of Cu/Zn-SOD. Differential expression of stress-responsive
      genes like Cu/Zn-SOD, catalase (CAT), heat shock protein 70 (Hsp70) and
      metallothionein (MT) was applied as potential biomarkers to assess their efficacy
      for the ecotoxicological effects of dietary zinc oxide (ZnO) on E. fetida. The
      results showed that the expression of Cu/Zn-SOD and MT increased to reach the
      highest levels of 6.22 and 7.68 fold in a dose-dependent manner at day 10
      respectively. The highest expression of 3.03 fold of CAT was registered at day
      10. The transient expression of Hsp70 without consistent time- or/and dose
      dependent was observed. It implied that the transcriptional patterns of Cu/Zn
      SOD, CAT and MT could serve as early warning signals in ecotoxicological
      assessment of dietary ZnO on earthworms while the expression of Hsp70 was not
      well done, which is helpful to monitoring and regulation of ZnO in veterinary
      application.

PMID- 22137963
TI  - Advanced bacterial polyhydroxyalkanoates: towards a versatile and sustainable
      platform for unnatural tailor-made polyesters.
AB  - Polyhydroxyalkanoates (PHAs) are biopolyesters that generally consist of 3-, 4-,
      5-, and 6-hydroxycarboxylic acids, which are accumulated as carbon and energy
      storage materials in many bacteria in limited growth conditions with excess
      carbon sources. Due to the diverse substrate specificities of PHA synthases, the
      key enzymes for PHA biosynthesis, PHAs with different material properties have
      been synthesized by incorporating different monomer components with differing
      compositions. Also, engineering PHA synthases using in vitro-directed evolution
      and site-directed mutagenesis facilitates the synthesis of PHA copolymers with
      novel material properties by broadening the spectrum of monomers available for
      PHA biosynthesis. Based on the understanding of metabolism of PHA biosynthesis,
      recombinant bacteria have been engineered to produce different types of PHAs by
      expressing heterologous PHA biosynthesis genes, and by creating and enhancing the
      metabolic pathways to efficiently generate precursors for PHA monomers. Recently,
      the PHA biosynthesis system has been expanded to produce unnatural biopolyesters
      containing 2-hydroxyacid monomers such as glycolate, lactate, and 2
      hydroxybutyrate by employing natural and engineered PHA synthases. Using this
      system, polylactic acid (PLA), one of the major commercially-available
      bioplastics, can be synthesized from renewable resources by direct fermentation
      of recombinant bacteria. In this review, we discuss recent advances in the
      development of the PHA biosynthesis system as a platform for tailor-made
      polyesters with novel material properties.

PMID- 22137964
TI  - A combination of nonionic surfactants and iontophoresis to enhance the
      transdermal drug delivery of ondansetron HCl and diltiazem HCl.
AB  - The present work reports the evaluation of three nonionic ether-monohydroxyl
      surfactants (C(12)E(1), C(12)E(5,) and C(12)E(8)) as skin permeation enhancers in
      the transdermal drug delivery of two drugs: ondansetron hydrochloride and
      diltiazem hydrochloride, formulated as hydrogels. The enhancers are used alone,
      or in combination with iontophoresis (0.3 mA - 8h). After 1h of pre-treatment
      with 0.16 M enhancer solutions in propylene glycol (PG), passive and
      iontophoretic 24 h in vitro studies across dermatomed porcine skin were performed
      using vertical Franz diffusion cells. Data obtained showed that the nonionic
      surfactant C(12)E(5) was the most effective permeation enhancer, both for the
      passive process as well as for samples subjected to iontophoresis, resulting in
      cumulative amounts of ondansetron HCl after 24h of approximately 93 MUg/cm(2) and
      336 MUg/cm(2), respectively. Data obtained using diltiazem HCl showed a similar
      trend. The use of the nonionic surfactant C(12)E(5) resulted in higher
      enhancement ratios (ER) in passive studies, but C(12)E(8) yielded slightly higher
      values of drug permeated (2678 MUg/cm(2)) than C(12)E(5) (2530 MUg/cm(2)) when
      iontophoresis was also employed. Skin integrity studies were performed to assess
      potential harmful effects on the tissues resulting from the compounds applied
      and/or from the methodology employed. Skin samples used in permeation studies
      visualized by light microscopy and Scanning Electron Microscopy (SEM) at
      different levels of magnification did not show significant morphological and
      structural changes, when compared to untreated samples. Complementary studies
      were performed to gain information regarding the relative cytotoxicity of the
      penetration enhancers on skin cells. MTS assay data using human epidermal
      keratinocytes (HEK) and human dermal fibroblasts (HDF) indicated that HEK are
      more sensitive to the presence of the enhancers than HDF and that the toxicity of
      these compounds is enhancer molecular weight dependent.

PMID- 22137965
TI  - Visual mismatch negativity and unintentional temporal-context-based prediction in
      vision.
AB  - Since the discovery of an event-related brain potential (ERP) component, auditory
      mismatch negativity (auditory MMN), there has been a long-lasting debate
      regarding the existence of its counterparts in other sensory modalities. Over the
      past few decades, several studies have confirmed the existence of mismatch
      negativity in the visual modality (visual MMN) and have revealed the various
      characteristics of visual MMN. In the present review, a full range of visual MMN
      studies are overviewed from the perspective of the predictive framework of visual
      MMN recently proposed by Kimura et al. (2011b). In the first half, the nature of
      visual MMN is reviewed in terms of (1) typical paradigm and morphologies, (2)
      underlying processes, (3) neural generators, and (4) functional significance. The
      main message in this part is that visual MMN is closely associated with the
      unintentional prediction of forthcoming visual sensory events on the basis of
      abstract sequential rules embedded in the temporal context of visual stimulation
      (i.e., "unintentional temporal-context-based prediction in vision"). In the
      second half, the nature of the unintentional prediction is discussed in terms of
      (1) behavioral indicators, (2) cognitive properties, and (3) neural substrates
      and mechanisms. As the main message in this part, I put forward a hypothetical
      model, which suggests that the unintentional prediction might be implemented by a
      bi-directional cortical network that includes the visual and prefrontal areas.

PMID- 22137966
TI  - A frequency band analysis of two-year-olds' memory processes.
AB  - Research on the functional meaning of EEG frequency bands during memory
      processing has only examined two developmental periods: infancy and from late
      childhood to adulthood. The purpose of this study was to examine changes in EEG
      power for three toddler EEG frequency bands (3-5Hz, 6-9Hz, 10-12Hz) during a
      verbal recall task. To this end, we asked three questions: (a) Which frequency
      band(s) discriminate baseline from memory processing?; (b) Which frequency
      band(s) differentiate between memory encoding and retrieval processes?; (c) Which
      frequency band(s) distinguish toddlers with high and low verbal recall
      performance? Analysis of 2-year-olds' (n=79) power values revealed that all three
      frequency bands differentiated the retrieval and encoding phases from the
      baseline phase; however, the particular regions that exhibited this dissociation
      varied. Retrieval-related increases in 3-5Hz (theta) power were widespread. Only
      the 3-5Hz and 6-9Hz bands distinguished encoding and retrieval processes;
      retrieval power values were higher than encoding power values. High and low
      verbal recall performers were discriminated by all frequency bands; high
      performers had greater power values than low performers. Thus, the 3-5Hz (theta)
      and 6-9Hz (alpha) bands were most informative about 2-year-olds' memory
      processes. Theta and alpha rhythms are critical to memory processes during late
      childhood and adulthood, and our findings provide initial evidence that these
      rhythms are also intricately linked to memory processing during toddlerhood.
      These findings are discussed in relation to behavioral changes in memory
      processes.

PMID- 22137967
TI  - Ultrafast hetero-nuclear 2D J-resolved spectroscopy.
AB  - Ultrafast techniques enable the acquisition of 2D NMR spectra in a single scan.
      In this study, we propose a new ultrafast experiment designed to record hetero
      nuclear (1)H-(13)C J-resolved spectra in a fraction of a second. The approach is
      based on continuous constant-time phase modulated spatial encoding followed by a
      J-resolved detection scheme. An optional isotopic filter is implemented to remove
      the signal arising from (1)H bound to (12)C. While the most evident application
      of the technique proposed in this paper is the direct measurement of one bond
      scalar (13)C-(1)H couplings for structural elucidation purposes, it also offers
      interesting potentialities for measuring (13)C isotopic enrichments in metabolic
      samples. The main features of this methodology are presented, and the analytical
      performances of the ultrafast hetero-nuclear J-resolved pulse sequence are
      evaluated on model samples.

PMID- 22137968
TI  - Multistability and oscillations in genetic control of metabolism.
AB  - Genetic control of enzyme activity drives metabolic adaptations to environmental
      changes, and therefore the feedback interaction between gene expression and
      metabolism is essential to cell fitness. In this paper we develop a new formalism
      to detect the equilibrium regimes of an unbranched metabolic network under
      transcriptional feedback from one metabolite. Our results indicate that one-to
      all transcriptional feedback can induce a wide range of metabolic phenotypes,
      including mono-, multistability and oscillatory behavior. The analysis is based
      on the use of switch-like models for transcriptional control and the exploitation
      of the time scale separation between metabolic and genetic dynamics. For any
      combination of activation and repression feedback loops, we derive conditions for
      the emergence of a specific phenotype in terms of genetic parameters such as
      enzyme expression rates and regulatory thresholds. We find that metabolic
      oscillations can emerge under uniform thresholds and, in the case of operon
      controlled networks, the analysis reveals how nutrient-induced bistability and
      oscillations can emerge as a consequence of the transcriptional feedback.

PMID- 22137971
TI  - Body odor attractiveness as a cue of impending ovulation in women: evidence from
      a study using hormone-confirmed ovulation.
AB  - Scent communication plays a central role in the mating behavior of many nonhuman
      mammals but has often been overlooked in the study of human mating. However, a
      growing body of evidence suggests that men may perceive women's high-fertility
      body scents (collected near ovulation) as more attractive than their low
      fertility body scents. The present study provides a methodologically rigorous
      replication of this finding, while also examining several novel questions. Women
      collected samples of their natural body scent twice--once on a low-fertility day
      and once on a high-fertility day of the ovulatory cycle. Tests of luteinizing
      hormone confirmed that women experienced ovulation within two days of their high
      fertility session. Men smelled each woman's high- and low-fertility scent samples
      and completed discrimination and preference tasks. At above-chance levels, men
      accurately discriminated between women's high- and low-fertility scent samples
      (61%) and chose women's high-fertility scent samples as more attractive than
      their low-fertility scent samples (56%). Men also rated each scent sample on
      sexiness, pleasantness, and intensity, and estimated the physical attractiveness
      of the woman who had provided the sample. Multilevel modeling revealed that, when
      high- and low-fertility scent samples were easier to discriminate from each
      other, high-fertility scent samples received even more favorable ratings compared
      with low-fertility scent samples. This study builds on a growing body of evidence
      indicating that men are attracted to cues of impending ovulation in women and
      raises the intriguing question of whether women's cycling hormones influence
      men's attraction and sexual approach behavior.

PMID- 22137969
TI  - Of P and Z: mitochondrial tRNA processing enzymes.
AB  - Mitochondrial tRNAs are generally synthesized as part of polycistronic
      transcripts. Release of tRNAs from these precursors is thus not only required to
      produce functional adaptors for translation, but also responsible for the
      maturation of other mitochondrial RNA species. Cleavage of mitochondrial tRNAs
      appears to be exclusively accomplished by endonucleases. 5'-end maturation in the
      mitochondria of different Eukarya is achieved by various kinds of RNase P,
      representing the full range of diversity found in this enzyme family. While
      ribonucleoprotein enzymes with RNA components of bacterial-like appearance are
      found in a few unrelated protists, algae, and fungi, highly degenerate RNAs of
      dramatic size variability are found in the mitochondria of many fungi. The
      majority of mitochondrial RNase P enzymes, however, appear to be pure protein
      enzymes. Human mitochondrial RNase P, the first to be identified and possibly the
      prototype of all animal mitochondrial RNases P, is composed of three proteins.
      Homologs of its nuclease subunit MRPP3/PRORP, are also found in plants, algae and
      several protists, where they are apparently responsible for RNase P activity in
      mitochondria (and beyond) without the help of extra subunits. The diversity of
      RNase P enzymes is contrasted by the uniformity of mitochondrial RNases Z, which
      are responsible for 3'-end processing. Only the long form of RNase Z, which is
      restricted to eukarya, is found in mitochondria, even when an additional short
      form is present in the same organism. Mitochondrial tRNA processing thus appears
      dominated by new, eukaryal inventions rather than bacterial heritage. This
      article is part of a Special Issue entitled: Mitochondrial Gene Expression.

PMID- 22137970
TI  - Hitting the brakes: termination of mitochondrial transcription.
AB  - Deficiencies in mitochondrial protein production are associated with human
      disease and aging. Given the central role of transcription in gene expression,
      recent years have seen a renewed interest in understanding the molecular
      mechanisms controlling this process. In this review, we have focused on the
      mostly uncharacterized process of transcriptional termination. We review how
      several recent breakthroughs have provided insight into our understanding of the
      termination mechanism, the protein factors that mediate termination, and the
      functional relevance of different termination events. Furthermore, the
      identification of termination defects resulting from a number of mtDNA mutations
      has led to the suggestion that this could be a common mechanism influencing
      pathogenesis in a number of mitochondrial diseases, highlighting the importance
      of understanding the processes that regulate transcription in human mitochondria.
      We discuss how these recent findings set the stage for future studies on this
      important regulatory mechanism. This article is part of a Special Issue entitled:
      Mitochondrial Gene Expression.

PMID- 22137973
TI  - Implications of obesity for tendon structure, ultrastructure and biochemistry: a
      study on Zucker rats.
AB  - The extracellular matrix consists of collagen, proteoglycans and non-collagen
      proteins. The incidence of obesity and associated diseases is currently
      increasing in developed countries. Obesity is considered to be a disease of
      modern times, and genes predisposing to the disease have been identified in
      humans and animals. The objective of the present study was to compare the
      morphological and biochemical aspects of the deep digital flexor tendon of lean
      (Fa/Fa or Fa/fa) and genetically obese (fa/fa) Zucker rats. Ultrastructural
      analysis showed the presence of lipid droplets in both groups, whereas
      disorganized collagen fibril bundles were observed in obese animals. Lean animals
      presented a larger amount of non-collagen proteins and glycosaminoglycans than
      obese rats. We propose that the overweight and lesser physical activity in obese
      animals may have provoked the alterations in the composition and organization of
      extracellular matrix components but a genetic mechanism cannot be excluded. These
      alterations might be related to organizational and structural modifications in
      the collagen bundles that influence the mechanical properties of tendons and the
      progression to a pathological state.

PMID- 22137974
TI  - Perioperative antibiotic prophylaxis in plastic surgery: a prospective study of
      1,100 adult patients.
AB  - BACKGROUND: Although guidelines for antibiotic prophylaxis to prevent surgical
      site infections (SSIs) exist, specific guidelines for plastic surgery are missing
      and there is a tendency towards excessive administration of antibiotics. A total
      of 1100 patients were prospectively studied according to an evidence-based
      protocol to investigate if limiting antibiotic prophylaxis to high-risk cases
      does increase the infection rate. METHODS: Between April 2009 and April 2010,
      1100 consecutive patients undergoing elective reconstructive or cosmetic
      procedures were enrolled. Procedures were classified into four groups, and
      prophylactic antibiotics were only administered perioperatively in 23.4% of
      cases, according to patient-related and procedure-related risk factors. RESULTS:
      The overall SSI incidence was 1.4% (1.1% for clean surgery and 3.8% for clean
      contaminated surgery). Oral oncologic surgery showed the highest infection rate
      (5.3%). CONCLUSIONS: Specific guidelines are provided to encourage judicious use
      of antibiotics. Antibiotic prophylaxis is administered based on the type of
      operation and the patient's characteristics. No prophylaxis was carried out in
      superficial skin surgery and simple mucosal excisions. Antibiotic prophylaxis is
      always indicated in microsurgery, prosthetic surgery, incisional hernias, clean
      non-prosthetic osteoarticular surgery and clean-contaminated procedures such as
      oral cavity or genitourinary system. In clean surgery and rhinoplasty, antibiotic
      prophylaxis is only indicated when the operation lasts more than 3 h and/or the
      American Society of Anesthesiologists (ASA) score is 3 or more. With the protocol
      reported, the risk of infection can be kept very low, avoiding the negative
      effects of indiscriminate use of antibiotics.

PMID- 22137972
TI  - Brainstem neuronal and behavioral activation by corticotropin-releasing hormone
      depend on the behavioral state of the animal.
AB  - Central administration of corticotropin-releasing hormone (CRH) is known to
      enhance locomotion across a wide range of vertebrates, including the roughskin
      newt, Taricha granulosa. The present study aimed to identify the CRH effects on
      locomotor-controlling medullary neurons that underlie the peptide's behavioral
      stimulating actions. Single neurons were recorded from the rostral medullary
      reticular formation before and after intraventricular infusion of CRH in freely
      behaving newts and newts paralyzed with a myoneural blocking agent. In behaving
      newts, most medullary neurons showed increased firing 3-23 min after CRH
      infusion. Decreases in firing were less common. Of particular importance was the
      finding that in behaving newts, medullary neurons showed a cyclic firing pattern
      that was strongly associated with an increase in the incidence of walking bouts,
      an effect blocked by pretreatment with the CRH antagonist, alpha-helical CRH and
      not seen following vehicle administration. In contrast, the majority of medullary
      neurons sampled in immobilized newts lacked temporal cyclicity in their firing
      patterns following intraventricular infusion of CRH. That is, there was no
      evidence for a fictive locomotor activity pattern. Our results indicate that the
      actual expression of locomotion is a critical factor in regulating the behavior
      activating effects of CRH and underscore the importance of using an awake,
      unrestrained animal for analysis of a hormone's neurobehavioral actions.

PMID- 22137975
TI  - Craniofacial neurofibromatosis and tissue expansion: long-term results.
AB  - The role of tissue expansion for coverage of soft-tissue defects of the face
      following neurofibroma resection has been briefly described previously with good
      results but limited follow-up. Recent scientific evidence has arisen that
      neurofibromas adversely affect the rheological properties of normal surrounding
      skin resulting in hyper-extensibility of dermal elements. In this context, we
      believe that long-term outcomes of tissue expansion for treatment of soft-tissue
      defects in patients with craniofacial neurofibromatosis would demonstrate
      suboptimal results because of loss of contour. Between June 1981 and June 2011,
      two patients underwent five tissue expander placements during the course of
      treatment for craniofacial neurofibromatosis at our institution. In both
      patients, tissue expansion was used to recruit tissue for fascio-cutaneous flaps
      following radical excision of adjacent neurofibromas. Three cervical expansions
      were performed for cheek and lateral face recontouring. One forehead expansion
      was used for nasal reconstruction and a second forehead expansion was performed
      for temporo-orbital recontouring. No perioperative complications occurred related
      to the tissue expander placement, expansions or radical excisions. Photographic
      follow-up of 15 years is available in each case. Cervical tissue expanded to
      provide cheek coverage demonstrated early loss of contour. Loss of lateral cheek
      contour resulted in increased morbidity from lateral and caudal displacement of
      the mid-face and orbital tissues requiring multiple revisional procedures. Tissue
      expansion of the forehead for both nasal reconstruction and temporo-orbital
      reconstruction demonstrated excellent long-lasting results.

PMID- 22137976
TI  - Upper limb salvage following near skeletalisation.

PMID- 22137977
TI  - Modification of flap design for total mobile tongue reconstruction using a
      sensitive antero-lateral thigh flap.
AB  - Reconstruction of large carcinologic tongue defect is mandatory to recover
      adequate speech and swallowing. Free flaps provide thin and pliable tissues
      needed to restore the shape and the volume of the tongue but their functional
      outcomes, especially in case of total mobile tongue reconstruction, are still
      limited. The authors describe a modification of flap design called the 'cathedral
      triptych' used with the antero-lateral thigh flap. This modified design recreates
      a near normal neotongue shape with more projected tip and vertical bulk that can
      contact the palate and the upper lip. Ten patients underwent total mobile tongue
      reconstruction with a sensitive antero-lateral thigh flap and a 'cathedral
      triptych' design. This modification of flap shaping and folding optimises
      postoperative oral function.

PMID- 22137978
TI  - The effect of hyperbaric oxygen therapy on the survival of random pattern skin
      flaps in nicotine-treated rats.
AB  - Previous studies have shown that nicotine increases the risk of necrosis in skin
      flaps. We investigated the effect of hyperbaric oxygen (HBO(2)) treatment on the
      survival of random skin flaps in nicotine-treated rats. Thirty-two Sprague-Dawley
      rats were divided into four groups with eight rats in each group. Group 1 (n=8)
      was the control, group 2 (n=8) received HBO(2) treatment without being exposed to
      nicotine, group 3 (n=8) received nicotine and group 4 (n=8) received HBO(2)
      treatment with exposure to nicotine. The rats in the nicotine-treated groups were
      prepared by treating them with nicotine for 28 days. At the end of the 28th day,
      standard McFarlane-type random skin flaps were lifted from the backs of all the
      rats. In groups 2 and 4, HBO(2) treatment started at the 30th min following the
      surgery and continued once a day for 7 days. The flap survival rates and
      histopathological evaluation results related to neovascularisation and
      granulation tissue formation were significantly better in the HBO(2)-treated
      groups (groups 2 and 4) than in the groups that did not receive HBO(2) treatment
      (groups 1 and 3) (p < 0.05). The flap survival rates, neovascularisation and
      granulation tissue formation were highest in group 2 and lowest in group 3 (p <=
      0.001). No significant difference was observed between group 4, which received
      HBO(2) treatment with nicotine exposure, and the control group (group 1) (p >
      0.05). In conclusion, our study demonstrates that HBO(2) treatment has a positive
      effect on flap survival in nicotine-treated rats.

PMID- 22137979
TI  - Value of muscle enzyme measurement in evaluating different neuromuscular
      diseases.
AB  - BACKGROUND: Muscle enzymes sometimes can provide clues for many similar
      neuromuscular disorders. However literatures that described and compared the
      muscle enzyme levels among these diseases are few. We described their changes in
      a group of Chinese patients. METHODS: We reviewed creatine kinase (CK), lactate
      dehydrogenase (LDH), aspartate transaminase (AST) levels and CK/lDH in Chinese
      patients with Duchene/Becker muscular dystrophy (DMD/BMD), facioscapulohumeral
      muscular dystrophy (FSHD), limb-girdle muscular dystrophy (LGMD), polymyositis
      (PM), lipid storage myopathy (LSM), motor neuron disease (MND) and spinal
      muscular atrophy (SMA). The diagnosis of DMD/BMD, FSHD, LSM and SMA was confirmed
      by genetic analysis. Comparisons between groups were tested by One-Way ANOVA
      analysis and LSD test. RESULTS: CK: DMD/BMD>PM>LGMD>LSM>FSHD>MND>SMA. LDH and
      AST: DMD/BMD>LSM>PM>LGMD>FSHD>SMA>MND. For MND, logCK in PMA is the highest. For
      SMA, logCK value in type III is the highest. LDH disproportionately elevates in
      LSM and SMA. CONCLUSION: This investigation described muscle enzyme profiles in a
      large cohort of Chinese patients with neuromuscular diseases. Muscle enzyme
      values may have some implications for making decision when the diagnosis is hard.

PMID- 22137980
TI  - Performance characteristics and patient comparison of the ARK Diagnostics
      levetiracetam immunoassay with an ultra-high performance liquid chromatography
      with tandem mass spectrometry detection method.

PMID- 22137981
TI  - No correlation between pretreatment serum CEA levels and tumor volume in locally
      advanced rectal cancer patients.
AB  - BACKGROUND: Although serum carcinoembryonic antigen (CEA) levels reflect tumor
      volume in rectal cancer patients intrapersonally, it is unclear interpersonally.
      We determined the correlation between pretreatment serum CEA levels and tumor
      volume. METHODS: A total of 489 patients with locally advanced primary rectal
      cancer who underwent preoperative chemoradiotherapy followed by surgery between
      October 2001 and April 2007 were retrospectively evaluated. CEA levels were
      measured by chemiluminescent microparticle immunoassay, and magnetic resonance
      (MR) volumetry was performed using MR data. The correlation between CEA levels
      and tumor volume was assessed using linear regression analysis and one-way
      analysis of variance. The prognostic values of CEA levels and tumor volume for
      survival were evaluated. RESULTS: There was no significant correlation between
      CEA levels and tumor volume. The five-year overall survival and disease-free
      survival were 89.0%, 80.6% and 82.9%, and 72.0%, 70.0% and 60.3% in patients with
      CEA levels of <=3 ng/ml, >3-10 ng/ml, and >10 ng/ml, respectively. Tumor volume
      had no prognostic value for either overall survival or disease-free survival
      CONCLUSIONS: Pretreatment serum CEA levels were not correlated with tumor volume.
      While there was no correlation between tumor volume and survival, there was a
      positive correlation between CEA levels and survival.

PMID- 22137982
TI  - Timing of fertility preservation procedures in a cohort of female patients with
      cancer.
AB  - OBJECTIVE: Comparison of time intervals from diagnosis to chemotherapy between
      patients opting for embryo cryopreservation or ovarian tissue cryopreservation.
      STUDY DESIGN: Retrospective analysis. SETTING: University hospital in the
      Netherlands. PATIENTS AND METHODS: Thirty-five female patients undergoing
      fertility preservation procedures before treatment with chemotherapy for cancer.
      Embryo cryopreservation was performed in 12 patients and ovarian tissue
      cryopreservation in 23 patients. We investigated differences in time intervals
      (from diagnosis to start of chemotherapy) between patients opting for embryo
      cryopreservation and patients opting for ovarian tissue cryopreservation. We
      calculated time intervals between the moment of diagnosis, the moment of
      referral, the moment of consultation, the moment of finishing of the fertility
      preservation procedure and the start of chemotherapy. RESULTS: The median time
      between diagnosis and referral (median=18 days) and between referral and
      consultation (median=5 days) was comparable in both groups. A significant
      difference was found between ovarian tissue cryopreservation and embryo
      cryopreservation for the time interval between consultation and cryopreservation
      (p=0.001). Ovarian tissue cryopreservation was completed for half of the patients
      within 6 days after consultation with the gynecologist, and the hormonal
      stimulation for embryo cryopreservation was completed for all patients within
      four weeks (median=18 days), with a median of 11 days of hormonal stimulation. A
      significant difference was found between ovarian tissue cryopreservation and
      embryo cryopreservation in the time interval between fertility preservation and
      start of chemotherapy (median=7 vs 19 days, p=0.019). In sum, the total duration
      between diagnosis and chemotherapy was significantly shorter for ovarian tissue
      cryopreservation patients than for embryo cryopreservation patients (median=47 vs
      69 days, p=0.042). CONCLUSION: Embryo cryopreservation can be performed within
      the standard timeframe of cancer care in patients with breast cancer receiving
      adjuvant chemotherapy, but if delay of the start of chemotherapy is harmful,
      ovarian tissue cryopreservation can be done within one week.

PMID- 22137983
TI  - Follow up of infertile patients after failed ART cycles: a preliminary report
      from Iran and Turkey.
AB  - OBJECTIVES: Assisted reproductive technology (ART) has become an established and
      increasingly successful form of treatment for infertility. However, significant
      numbers of cycles fail after embryo transfer (ET) and it becomes necessary to
      follow up the infertile couples after failed ART treatments. The main goal was to
      follow up the infertile patients after failed IVF/ICSI+ET treatments in Iran and
      Turkey. STUDY DESIGN: 198 infertile couples from Iran and 355 infertile couples
      from Turkey were followed up after IVF/ICSI failures. The patients' demographic
      data, the couples' decisions about continuation of treatment and the spontaneous
      pregnancy rates were compared in the two countries. RESULTS: The drop-out rate
      was higher in Iran (28.3%) than in Turkey (23.4%). The reasons for treatment
      discontinuation in Iran and Turkey were: financial problem (33.9% vs. 41%),
      hopeless (10.7% vs. 22.9%), fear of drug side-effects (7.1% vs. 12%), achieving
      pregnancy (37.5% vs. 19.6%), child adoption (5.4% vs. 2.4%), lack of spouse
      cooperation (5.4% vs. 2.4%), and divorce (0% vs. 2.4%). Spontaneous pregnancy was
      significantly higher in Iran (10.1%) than in Turkey (3.9%). There was correlation
      between duration of infertility and female factor infertility with spontaneous
      pregnancy. CONCLUSIONS: Since the majority of couples that discontinued treatment
      had financial problems, it is essential for health professionals to support
      infertile couples during their childlessness crisis.

PMID- 22137984
TI  - Introduction of metformin for gestational diabetes mellitus in clinical practice:
      Has it had an impact?
AB  - OBJECTIVE: The aim of the study was to compare maternal and neonatal outcomes in
      women with gestational diabetes mellitus (GDM) treated with metformin in addition
      to the dietary and lifestyle advice versus those treated traditionally with
      dietary and lifestyle advice only. STUDY DESIGN: A retrospective study of
      singleton pregnancies in women with GDM delivered between January 2008 to June
      2010 (n=592) at the Jessop Wing, Royal Hallamshre Hospital, UK. Introduction of
      metformin in August 2008 led to two comparable groups, those women receiving
      metformin, lifestyle advice (including dietary advice) +/- supplementary insulin
      and those women receiving lifestyle advice (including dietary advice) +/-
      supplementary insulin. Two hundred and ninety three women were treated with
      metformin and lifestyle advice and remaining 299 with lifestyle advice only.
      Supplementary insulin was used in both the groups if needed. Outcomes were
      analyzed using the chi-squared and t-tests. RESULTS: There were no significant
      differences in baseline maternal characteristics between the two groups.
      Metformin was tolerated throughout the pregnancy by 90% of the women in the
      metformin+lifestyle advice group. Supplementary insulin was required by 21% in
      the metformin+lifestyle advice group compared to 37% in the lifestyle advice
      group (OR 0.46; 95% CI 0.32-0.66). Women in the metformin group had a
      significantly lower incidence of macrosomia (birth weight>4kg) (8.2% vs. 14.3%
      (OR 0.56; 95% CI 0.33-0.99)), as well as birth weight >90th centile (14.8% vs.
      23.7% (OR 0.56; 95% CI 0.37-0.85)). There were no significant differences in
      maternal outcome measures between the groups. No serious maternal or neonatal
      adverse events were observed with the use of metformin. CONCLUSION: Metformin is
      safe and effective in the treatment of GDM in our experience. It is well
      tolerated and reduces the requirement for supplementary insulin. Women treated
      with metformin had a significantly lower incidence of macrosomic and large for
      gestational age neonates as well as a reduced caesarean section rate.

PMID- 22137985
TI  - Eversion endarterectomy of the proximal superficial femoral artery: a source of
      inflow for distal bypass in case of hostile groin.
AB  - BACKGROUND: In selected patients, eversion endarterectomy of the proximal
      superficial femoral artery can represent a valid inflow for a distal bypass to
      avoid a "hostile" groin. MATERIAL AND METHODS: Patency rates and limb salvage
      rates were retrospectively analysed for 21 consecutive patients who underwent
      distal bypass for severe lower limb ischemia and in whom the proximal superficial
      femoral artery was reopened with an eversion endarterectomy. In all patients,
      this technique was used to avoid a hostile groin. RESULTS: Five-year cumulative
      patency rates were 53% for femoropopliteal bypasses and 40% for femorotibial
      bypasses. Overall 5-y cumulative limb salvage was 72%. CONCLUSIONS: In case of
      hostile groin, eversion endarterectomy of the proximal superficial femoral artery
      is a valid solution to provide inflow for a distal bypass.

PMID- 22137986
TI  - Protective effect of pharmacologic preconditioning with pioglitazone on random
      pattern skin flap in rat is mediated by nitric oxide system.
AB  - BACKGROUND: Pioglitazone, a thiazolidinedione, is primarily used as an
      antidiabetic agent. In addition, recent reports have identified anti-ischemic and
      anti-inflammatory properties of pioglitazone through nitric oxide (NO) pathways.
      OBJECTIVE: To determine the protective effects of pioglitazone on random-pattern
      skin flaps in a rat model. METHODS: Forty-eight male Rats were randomly assigned
      to eight groups. Bipedicled dorsal skin flaps (2 * 8 cm) were elevated at the
      midline. In pharmacologic preconditioning groups, three different doses of
      pioglitazone (25, 40, 80, mg/kg; doses were selected according to our pilot
      study) gavaged 4 h before elevating flaps. Seven days after operation, the
      survival of skin flap was measured. For investigating the role of NO system, in
      other groups the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester
      hydrochloride (L-NAME, 10 mg/kg) was administered alone or with an effective dose
      of pioglitazone. Finally, in another group, subeffective dose of nitric oxide
      precursor L-arginine (100 mg/kg) was coadministered with subeffective
      pioglitazone. RESULTS: Significant increase in flap survival was seen with
      pioglitazone (40 mg/kg). This protective effect was abolished by systemic
      administration of L-NAME (10 mg/kg). Coadministration of subeffective doses of
      pioglitazone with subeffetcive L-arginine significantly improved flap survival.
      CONCLUSION: Pharmacologic preconditioning with pioglitazone improves survival of
      random-pattern skin flaps in rats through NO dependent mechanisms.

PMID- 22137987
TI  - Effect of polyethylene glycol in pig intestinal allotransplantation without
      immunosuppression.
AB  - OBJECTIVES: We evaluated whether IGL-1, a graft preservation solution containing
      polyethylene glycol, improves the outcome of small bowel grafts in comparison to
      the University of Wisconsin (UW) solution in a pig allotransplantation model.
      MATERIALS AND METHODS: Seventeen pigs were randomly allocated to group 1 (n = 10;
      intestinal allotransplantation with IGL-1) and group 2 (n = 7;
      allotransplantation with UW). Pigs received no immunosuppression and were
      sacrificed on postoperative d (POD) 8. Intestinal specimens were obtained from
      the animal immediately before cold flushing (T0), 2 h after graft reperfusion
      (T1), and at sacrifice (T2). RESULTS: Survival rate to POD 8 was 50% in group 1
      compared with 16% in group 2 (P < 0.05); 62% of pigs in group 1 did not present
      any acute cellular rejection (ACR) compared to 16% in group 2 (P < 0.05). Severe
      ACR rate was 25% in group 1 and 66% in group 2 (P < 0.05). iNOS activity and
      intestinal caspase 3 levels increased significantly between T0 and T1 in group 1
      compared to group 2 (P < 0.05). Cell necrosis increased significantly between TO
      and T1 in group 2 compared with group 1 (P < 0.05) whereas cell apoptosis was
      significantly higher at T1 compared with T0 in group 1 in comparison to group 2.
      CONCLUSIONS: Our results show that IGL-1 improves intestinal graft viability as
      compared to UW solution, possibly by reducing graft immunogenicity and by
      favoring intestinal epithelial repair.

PMID- 22137988
TI  - Ghrelin level and body weight loss after esophagectomy for esophageal cancer.
AB  - BACKGROUND: Ghrelin is a peptide hormone predominantly produced by endocrine
      cells in the oxyntic mucosa of the stomach and is an endogenous ligand for the
      growth hormone secretagogue receptor. Ghrelin plays an important role in
      regulating appetite, food intake, and energy metabolism. We investigated the
      correlation between clinicopathologic factors and plasma ghrelin concentration
      before and after esophagectomy with gastric tube reconstruction for esophageal
      cancer treatment. METHODS: The study group comprised 25 patients (22 men, three
      women, age range 46-78 y) with esophageal cancer who underwent esophagectomy with
      gastric tube reconstruction between 1999 and 2007. Blood samples were collected
      before and three times after the operation. Plasma concentrations of ghrelin were
      determined using a sandwich-type enzyme immunoassay kit. RESULTS: Plasma ghrelin
      concentrations were significantly decreased to 38.7% of the preoperative
      concentration at postoperative d 7. Plasma ghrelin concentrations recovered
      slightly over 6-24 mo postoperatively. After 36 mo or longer, ghrelin
      concentrations had returned to preoperative levels. There was no relationship
      between ghrelin concentrations and gender, location of tumor, tumor stage,
      operative procedure, and reconstruction route at each time point. There was a
      significant relationship between the decrease in body mass index and decrease in
      plasma ghrelin in patients at 6-24 mo after esophagectomy (P < 0.01).
      CONCLUSIONS: Plasma ghrelin concentrations decrease on a temporary basis after
      esophagectomy with gastric tube reconstruction and are associated with body
      weight loss after surgery.

PMID- 22137989
TI  - Darbepoetin-alpha promotes neovascularization and cell proliferation in
      established colorectal liver metastases.
AB  - BACKGROUND: The erythropoietin-analogue darbepoetin-alpha (DPO) improves liver
      function and regeneration after hepatectomy (Phx), however, also enhances Phx
      induced tumor cell engraftment and neovascularization. Because it is unknown
      whether DPO also enhances the growth of established tumors, we herein studied the
      effect of DPO on established colorectal liver metastases after Phx. METHODS:
      CT26.WT cells were implanted into the liver of BALB/c mice. Five days after tumor
      establishment, animals underwent 50% Phx and received 10 MUg/kgBW DPO or saline.
      Non-Phx animals with DPO or saline-treatment served as controls. Seven days after
      Phx tumors were analyzed regarding blood vessel formation, leukocyte adhesion,
      cell proliferation, apoptotic cell death, and growth using intravital
      fluorescence microscopy, histology, and immunohistochemistry. RESULTS: The growth
      of established colorectal liver metastases was slightly stimulated after DPO
      treatment in hepatectomized and non-hepatectomized animals. However, tumor vessel
      formation and tumor cell proliferation were significantly enhanced after DPO
      treatment in hepatectomized and non-hepatectomized mice compared with controls.
      Apoptotic cell death and leukocyte-endothelial cell interaction were
      significantly reduced after DPO-treatment. CONCLUSION: Our study indicates that
      DPO-treatment promotes neovascularization and cell proliferation in established
      colorectal liver metastases of hepatectomized and non-hepatectomized mice. DPO
      application in patients with colorectal liver metastases might promote tumor
      progression and should therefore be avoided.

PMID- 22137990
TI  - [Expanded newborn screening in the Region of Murcia, Spain. Three-years
      experience].
AB  - BACKGROUND AND OBJECTIVE: The early detection of inborn errors of metabolism by
      mass spectrometry allows expanding the traditional neonatal screening of
      phenylketonuria and congenital hypothyroidism to test for aminoacidopathies,
      fatty acid oxidation disorders and organic acid metabolic disorders. Cystic
      fibrosis and biotinidase deficiency screening is implemented in the Region of
      Murcia. The aim of the study is to describe our experience in the expanded
      neonatal screening and to define the prevalence of each of the metabolic
      disorders early detected. PATIENTS AND METHODS: Since March 2007 until October
      2010, a total of 71,595 neonates were screened with this expanded program by mass
      spectrometry, fluoroimmunoassay or colorimetric methods. RESULTS: Thirty-eight
      patients (prevalence 1:1,884) were diagnosed of inborn errors of metabolism by
      mass spectrometry, 13 patients of cystic fibrosis (prevalence 1:5,507), 38 of
      congenital hypothyroidism (prevalence 1:1,884) and one of biotinidase deficiency.
      To date, the global frequency of inborn errors of metabolism is estimated to be
      1:804. The positive predictive value for the results obtained by mass
      spectrometry was 20.25%. Two false negative patients were not identified (cystic
      fibrosis and methylmalonic aciduria patients) and 6 non neonatal patients were
      detected through expanded neonatal screening. CONCLUSIONS: Our data support the
      necessity of unifying the set of metabolic diseases to be screened in all Regions
      of Spain for early detection of a defined panel of inborn errors of metabolism
      and to provide every newborn the same opportunities to be early diagnosed.

PMID- 22137991
TI  - [Rapidly progressive endocarditis].

PMID- 22137992
TI  - [Hot water-induced epileptic crisis].

PMID- 22137993
TI  - [Emergencies in chronic obstructive pulmonary disease].

PMID- 22137994
TI  - [Outpatient management of patients with deep vein thrombosis and cancer: a study
      of safety, cost and budget impact].
AB  - BACKGROUND AND OBJECTIVE: This is a safety and cost comparison study with an
      analysis of budgetary impact of ambulatory management of patients with cancer and
      deep vein thrombosis (DVT) compared with hospital management. MATERIAL AND
      METHODS: Prospective observational study of patients with known malignancy and
      diagnosed with DVT from 2003 to 2007. The outcome variables were mortality,
      relapse and bleeding in one month. We conducted an economic analysis to evaluate
      the comparative cost of ambulatory patients. RESULTS: Three hundred and seventeen
      patients, 55 (17%) had cancer. The mean age of patients was 63 +/- 11 years.
      There were 2 hemorrhagic events, 2 recurrences and 6 deaths in one month of
      follow-up. Of all patients, only 7 (13,7%) required hospitalization. All but one
      deaths were due to progression of the underlying disease. Economic analysis
      concluded that outpatient management is 6 times less expensive than hospital
      management, which would imply a cost reduction of 85%. CONCLUSIONS: Specialized
      outpatient treatment of cancer patients with DVT is safe and could save
      significant financial resources.

PMID- 22137995
TI  - [Avascular necrosis of the hip in a patient with HIV infection].

PMID- 22137996
TI  - [Severe imatinib-induced hepatotoxicity].

PMID- 22137998
TI  - [The culture of confidentiality in Northern Spain hospitals].

PMID- 22137999
TI  - Development of a pilot-scale manufacturing process for protein-coated
      microcrystals (PCMC): mixing and precipitation - part I.
AB  - A novel protein-coated microcrystal (PCMC) technology offers the possibility to
      produce dry protein formulations suitable for inhalation or, after
      reconstitution, for injection. Micron-sized particles are hereby produced by co
      precipitation via a rapid dehydration method. Thus, therapeutic proteins can be
      stabilised and immobilised on crystalline carrier surfaces. In this study, the
      development of a continuous manufacturing process is described, which can produce
      grams to kilograms of PCMC. The process chain comprises three steps:
      mixing/precipitation, solvent reduction (concentration) and final drying. The
      process is published in two parts. This part describes the mixing and
      precipitation performed using continuous impingement jet mixers. Mixing
      efficiency was improved by dividing the anti-solvent flow into two or four jets,
      which were combined again inside the mixer to achieve an embracing of the aqueous
      solution (sandwich effect). The jets provided high energy dissipation rates. The
      anti-solvent jets (95% of the total volume) efficiently mixed the protein-carrier
      containing aqueous solution (5% of the total volume), which was demonstrated with
      computational fluid dynamics and the Villermaux-Dushman reaction. The improved
      mixing performance of the double jet impingement (DJI) or the quadruple jet
      impingement (QJI) mixers showed a positive effect on easily crystallising
      carriers (e.g. dl-valine) at laminar flow rates. The mixer and outlet tube bore
      size was 2.0-3.2 mm, because smaller sizes showed a high tendency to block the
      mixer. The mixing effect by impaction was sufficiently high in the flow rate
      range of 250-2000 mL/min, which corresponds to the transition from laminar to
      turbulent flow characteristics. At lower flow rates, mixing was enhanced by
      ultrasound. 50-80L PCMC suspension was readily produced with the QJI mixer.

PMID- 22138000
TI  - Stimuli-responsive hydrogels for controlled pilocarpine ocular delivery.
AB  - A series of vinyl hydrogels containing alpha-aminoacid (L-histidine, L-valine)
      residues was synthesized and their swelling properties evaluated at different pHs
      and temperatures. Unlike the zwitterionic compound containing only the l
      histidine, a dual-stimuli responsiveness was improved in the carboxyl acid
      hydrogels carrying the l-valine residues (HVa). Besides the COOH functionality,
      the presence of either isopropyl and amido groups in the monomer structure
      renders the hydrogel also temperature-responsive, in a similar manner as the well
      known poly(N-isopropylacrylamide) (pNIPAAm). The three HVa hydrogels (cross
      linked with 1, 2, and 5 mol% of N,N'-ethylene-bisacrylamide, EBA) show a phase
      separation at the same critical pH4, although a different swelling was improved
      by the amount of EBA. In buffered solutions, the effect of increasing temperature
      led to decrease the swelling and, as the pH is close to the critical one, a
      further and sharper collapse of the hydrogel may be tuned. The release study of
      pilocarpine in physiological conditions showed a burst effect within the first
      few hours, followed by a sustained release for a week. The initial burst effect
      was strongly dependent on the kind of hydrogel investigated. As the pilocarpine
      is a basic molecule (pK(a)7.2), it may interact more strongly with the free
      carboxyl groups in the ionized state of the HVa hydrogels than the zwitterionic
      species of the histidine compounds. The releasing profile shows a three time
      greater release of the pilocarpine loaded in the HVa hydrogels. The hydrogels
      were found to be non-toxic against the mouse fibroblast NIH3T3 cells. The
      presence of pilocarpine strongly increased the cell proliferation even after 2
      days.

PMID- 22138001
TI  - The challenge of NSCLC diagnosis and predictive analysis on small samples.
      Practical approach of a working group.
AB  - Until recently, the division of pulmonary carcinomas into small cell lung cancer
      (SCLC) and non-small cell lung cancer (NSCLC) was adequate for therapy selection.
      Due to the emergence of new treatment options subtyping of NSCLC and predictive
      testing have become mandatory. A practical approach to the new requirements
      involving interaction between pulmonologist, oncologist and molecular pathology
      to optimize patient care is described. The diagnosis of lung cancer involves (i)
      the identification and complete classification of malignancy, (ii)
      immunohistochemistry is used to predict the likely NSCLC subtype (squamous cell
      vs. adenocarcinoma), as in small diagnostic samples specific subtyping is
      frequently on morphological grounds alone not feasible (NSCLC-NOS), (iii)
      molecular testing. To allow the extended diagnostic and predictive examination
      (i) tissue sampling should be maximized whenever feasible and deemed clinically
      safe, reducing the need for re-biopsy for additional studies and (ii) tissue
      handling, processing and sectioning should be optimized. Complex diagnostic
      algorithms are emerging, which will require close dialogue and understanding
      between pulmonologists and others who are closely involved in tissue acquisition,
      pathologists and oncologists who will ultimately, with the patient, make
      treatment decisions. Personalized medicine not only means the choice of treatment
      tailored to the individual patient, but also reflects the need to consider how
      investigative and diagnostic strategies must also be planned according to
      individual tumour characteristics.

PMID- 22138002
TI  - Anaemia in pregnancy.
AB  - Anaemia in pregnancy, defined as a haemoglobin concentration (Hb) < 110 g/L,
      affects more than 56 million women globally, two thirds of them being from Asia.
      Multiple factors lead to anaemia in pregnancy, nutritional iron deficiency
      anaemia (IDA) being the commonest. Underlying inflammatory conditions,
      physiological haemodilution and several factors affecting Hb and iron status in
      pregnancy lead to difficulties in establishing a definitive diagnosis. IDA is
      associated with increased maternal and perinatal morbidity and mortality, and
      long-term adverse effects in the new born. Strategies to prevent anaemia in
      pregnancy and its adverse effects include treatment of underlying conditions,
      iron and folate supplementation given weekly for all menstruating women including
      adolescents and daily for women during pregnancy and the post partum period, and
      delayed clamping of the umbilical cord at delivery. Oral iron is preferable to
      intravenous therapy for treatment of IDA. B12 and folate deficiencies in
      pregnancy are rare and may be due to inadequate dietary intake with the latter
      being more common. These vitamins play an important role in embryo genesis and
      hence any relative deficiencies may result in congenital abnormalities. Finding
      the underlying cause are crucial to the management of these deficiencies.
      Haemolytic anaemias rare also rare in pregnancy, but may have life-threatening
      complications if the diagnosis is not made in good time and acted upon
      appropriately.

PMID- 22138003
TI  - Health economics of screening for gynaecological cancers.
AB  - In this chapter, we summarise findings from recent cost-effectiveness analyses of
      screening for cervical cancer and ovarian cancer. We begin with a brief summary
      of key issues that affect the cost-effectiveness of screening, including disease
      burden, and availability and type of screening tests. For cervical cancer, we
      discuss the potential effect of human papilloma virus vaccines on screening.
      Outstanding epidemiological and cost-effectiveness issues are included. For
      cervical cancer, this includes incorporating the long-term effect of treatment
      (including adverse birth outcomes in treated women who are of reproductive age)
      into cost-effectiveness models using newly available trial data to identify the
      best strategy for incorporating human papilloma virus tests. A second issue is
      the need for additional data on human papilloma virus vaccines, such as
      effectiveness of reduced cancer incidence and mortality, effectiveness in
      previously exposed women and coverage. Definitive data on these parameters will
      allow us to update model-based analyses to include more realistic estimates, and
      also potentially dramatically alter our approach to screening. For ovarian
      cancer, outstanding issues include confirming within the context of a trial that
      screening is effective for reducing mortality and incorporating tests with high
      specificity into screening into screening algorithms for ovarian cancer.

PMID- 22138004
TI  - Age differences on ERP old/new effects for emotional and neutral faces.
AB  - This study used event-related potentials (ERPs) to examine age differences in
      recognition memory for negative and neutral faces that systematically varied in
      facial expression during encoding and retrieval. During study, younger and older
      participants viewed negative and neutral faces and were asked to classify each
      facial expression. During test, half of the facial identities changed their
      facial expression, while the other half showed the same facial expression.
      Participants were asked to give old/new judgments to the depicted person. Four
      main findings were observed. First, when facial emotion did not switch from study
      to test, negative and neutral faces evoked spatially dissociable ERP old/new
      effects, independent of age. This suggests that different retrieval mechanisms
      contributed to successful recognition of negative and neutral faces in both age
      groups. Second, faces encoded with a negative expression evoked an early
      occipital old/new effect only in the young, perhaps suggesting superior memory
      for visual information. Third, faces retrieved with a negative expression evoked
      in both age groups an early parietal old/new effect, suggesting that negative
      emotion during retrieval facilitated memory access. Hence, in the early time
      latency in young adults both encoding-related and retrieval-related emotion
      effects contributed to face recognition memory, whereas in older adults encoding
      related emotion effects were reduced and retrieval-related emotion effects were
      preserved. Finally, in the late time latency perceptual similarity between study
      and test faces modified or overruled encoding-related emotion effects in the
      young and retrieval-related emotion effects in both age groups, respectively.

PMID- 22138005
TI  - Nuclear proteome analysis of benzo(a)pyrene-treated HeLa cells.
AB  - Previously, we employed a proteomics-based 2-D gel electrophoresis assay to show
      that exposure to 10MUM benzo(a)pyrene (BaP) during a 24 h frame can lead to
      changes in nuclear protein expression and alternative splicing. To further expand
      our knowledge about the DNA damage response (DDR) induced by BaP, we investigated
      the nuclear protein expression profiles in HeLa cells treated with different
      concentrations of BaP (0.1, 1, and 10MUM) using this proteomics-based 2-D gel
      electrophoresis assay. We found 125 differentially expressed proteins in BaP
      treated cells compared to control cells. Among them, 79 (63.2%) were down
      regulated, 46 (36.8%) were up-regulated; 8 showed changes in the 1MUM and 10MUM
      BaP-treated groups, 2 in the 0.1MUM and 10MUM BaP-treated groups, 4 in the 0.1MUM
      and 1MUM BaP-treated groups, and only one showed changes in all three groups.
      Fifty protein spots were chosen for liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) identification, and of these, 39 were identified,
      including subunits of the 26S proteasome and Annexin A1. The functions of some
      identified proteins were further examined and the results showed that they might
      be involved in BaP-induced DDR. Taken together, these data indicate that
      proteomics is a valuable approach in the study of environmental chemical-host
      interactions, and the identified proteins could provide new leads for better
      understanding BaP-induced mutagenesis and carcinogenesis.

PMID- 22138006
TI  - Impact of prosthesis-patient mismatch on the regression of secondary mitral
      regurgitation after isolated aortic valve replacement with a bioprosthetic valve
      in patients with severe aortic stenosis.
AB  - BACKGROUND: Secondary mitral regurgitation (SMR) is generally reduced after
      isolated aortic valve replacement (AVR), but there is important interindividual
      variability in the magnitude of this reduction. Prosthesis-patient mismatch (PPM)
      may hinder normalization of left ventricular geometry and pressure overload
      following AVR, therefore we aimed to investigate the relationship between PPM and
      regression of SMR following AVR for aortic valve stenosis. METHODS AND RESULTS: A
      total of 419 patients with AS who underwent isolated AVR at 2 institutions and
      presenting moderate SMR (mitral regurgitant volume 30 to 45 mL/beat) not
      considered for surgical correction were included in this study. Clinical and
      echocardiographic follow-up were completed at a median follow-up time of 37
      months. PPM was defined as an indexed effective orifice area <=0.85 cm(2)/m(2)
      and was found in 170/419 patients (40.6%). There were no significant differences
      in baseline and operative characteristics between patients with or without PPM.
      Patients with PPM had less regression of SMR following AVR compared with those
      with no PPM (change in mitral regurgitant volume: -11+/-4 versus -17+/-5 mL,
      respectively; P<0.0001). Variables significantly associated with postoperative
      change in mitral regurgitant volume on univariable analysis were entered in a
      multivariable linear regression model, which showed indexed effective orifice
      area (P<0.0001) and left atrial diameter (P=0.006) to be independently associated
      with mitral regurgitant volume improvement. Patients with PPM also had less
      postoperative improvement in 6-minute walking test distance (80+/-78 versus 42+/
      41 m, P<0.0001). CONCLUSIONS: PPM is associated with lesser regression of SMR
      following AVR. This unfavorable effect was associated with worse functional
      capacity. These findings emphasize the importance of operative strategies aiming
      to prevent PPM in patients with aortic valve stenosis and concomitant SMR.

PMID- 22138007
TI  - Biochemical markers in heart failure.
AB  - In industrialized countries, chronic heart failure (HF) is a major illness and
      cause of death. However, because of the paucity of specific clinical
      manifestations of HF, its early diagnosis and management might be challenging.
      Therefore, biochemical markers of HF are now being closely scrutinized. An ideal
      biochemical marker should be a prognostic indicator, should assist in the early
      diagnosis, reflect the therapeutic response, and help grading the risk associated
      with each stage of HF. This review summarizes our current understanding of
      biochemical markers of HF.

PMID- 22138008
TI  - Decision making after pediatric traumatic brain injury: trajectory of recovery
      and relationship to age and gender.
AB  - The aim of the study was to examine longitudinal patterns of decision making
      based on risk and reward using a modified version of the Iowa Gambling Task (IGT)
      in children who had sustained traumatic brain injury (TBI) and children with
      orthopedic injury (OI). Participants were 135 children and adolescents with TBI
      (n=71) or OI (n=64) who were 7-17 years at the time of injury were enrolled and
      assessed prospectively at baseline and at follow-up intervals of 3, 12, 18, and
      24 months after injury. Groups were similar in age, socioeconomic status, and
      gender. Participants chose from four decks of cards with the aim of maximizing
      earnings across 100 trials. Two of the decks offered relatively small rewards and
      relatively small losses, but were advantageous over the course of the experiment.
      The other two decks offered large rewards, but also introduced occasional large
      losses, and were considered disadvantageous over the course of the experiment.
      The variable of interest was the proportion of advantageous decks chosen across
      trials. Longitudinal analysis of the pattern of change across 2 years revealed a
      three-way interaction among injury group, age, and the quadratic term of interval
      since-injury. In this interaction, the effect of age weakened in the TBI group
      across time, as compared to the OI group, which showed stronger quadratic
      patterns across the recovery intervals that differed by age. The OI group
      generally outperformed the TBI group. In addition, analyses revealed a three-way
      interaction among group, gender and the cubic term of post-injury interval, such
      that overall, males improved a great deal with time, but females showed small
      gains, regardless of injury group.

PMID- 22138009
TI  - NCCN Task Force report: Evaluating the clinical utility of tumor markers in
      oncology.
AB  - The molecular analysis of biomarkers in oncology is rapidly advancing, but the
      incorporation of new molecular tests into clinical practice will require a
      greater understanding of the genetic changes that drive malignancy, the assays
      used to measure the resulting phenotypes and genotypes, and the regulatory
      processes that new molecular biomarkers must face to be accepted for clinical
      use. To address these issues and provide an overview of current molecular testing
      in 6 major malignancies, including glioma, breast cancer, colon cancer, lung
      cancer, prostate cancer, and acute myelogenous leukemia, an NCCN Task Force was
      convened on the topic of evaluating the clinical utility of tumor markers in
      oncology. The output of this meeting, contained within this report, describes the
      ways biomarkers have been developed and used; defines common terminology,
      including prognostic, predictive, and companion diagnostic markers, and analytic
      validity, clinical validity, and clinical utility; and proposes the use of a
      combination level of evidence score to aid in the evaluation of novel biomarker
      tests as they arise. The current state of regulatory oversight and anticipated
      changes in the regulation of molecular testing are also addressed.

PMID- 22138010
TI  - Using liquid crystals for the label-free detection of catalase at aqueous-LC
      interfaces.
AB  - In this study, we developed a simple label-free method for the detection of
      catalase (CAT) using liquid crystals (LCs). The optical appearance of LCs changed
      from bright to dark when hydrogen peroxide was in contact with the dodecanal
      doped nematic LC, 4-cyano-4'-pentylbiphenyl (5CB). Since hydrogen peroxide can
      oxidize aldehyde into carboxylic acid, an orientational transition of the LC from
      the planar to homeotropic state was induced by the self-assembled carboxylate
      monolayer formed at the aqueous/LC interface. The optical response of LCs
      exhibited a higher sensitivity to the presence of hydrogen peroxide in an
      alkaline solution. A new type of LC-based sensor was developed to monitor the
      presence of CAT in the aqueous phase. Due to the enzymatically catalytic
      hydrolysis of hydrogen peroxide, the bright-to-dark shift in the optical signal
      did not take place in the aqueous mixture of hydrogen peroxide and catalase. In
      contrast, the optical response changed from bright to dark when the mixture in
      the optical cell was replaced with an aqueous solution of hydrogen peroxide.
      Considering the optical response of LCs related to the absence and presence of
      hydrogen peroxide, the aldehyde-doped 5CB might have potential utility in real
      time recognition and detection of chemical and biological events associated with
      hydrogen peroxide.

PMID- 22138011
TI  - Proliferation assays for estrogenicity testing with high predictive value for the
      in vivo uterotrophic effect.
AB  - Proliferation assays based on human cell lines are the most used in vitro tests
      to determine estrogenic properties of compounds. Our objective was to
      characterise to what extent these in vitro tests provide alternatives for the in
      vivo Allen and Doisy test, a uterotrophic assay in immature or ovariectomised
      rodents with uterus weight as a crucial read-out parameter. In the present study
      four different human cell lines derived from three different female estrogen
      sensitive tissues, i.e. breast (MCF-7/BOS and T47D), endometrial (ECC-1) and
      ovarian (BG-1) cells, were characterised by investigating their relative ERalpha
      and ERbeta amounts, as the ERalpha/ERbeta ratio is a dominant factor determining
      their estrogen-dependent proliferative responses. All four cell lines clearly
      expressed the ERalpha type and a very low but detectable amount of ERbeta on both
      the mRNA and protein level, with the T47D cell line expressing the highest level
      of the ERbeta type. Subsequently, a set of reference compounds representing
      different modes of estrogen action and estrogenic potency were used to
      investigate the proliferative response in the four cell lines, to determine which
      cell line most accurately predicts the effect observed in vivo. All four cell
      lines revealed a reasonable to good correlation with the in vivo uterotrophic
      effect, with the correlation being highest for the MCF-7/BOS cell line (R2=0.85).
      The main differences between the in vivo uterotrophic assay and the in vitro
      proliferation assays were observed for tamoxifen and testosterone. The
      proliferative response of the MCF-7/BOS cells to testosterone was partially
      caused by its conversion to estradiol by aromatase or via androstenedione to
      estrone. It is concluded that of the four cell lines tested, the best assay to
      include in an integrated testing strategy for replacement of the in vivo
      uterotrophic assay is the human MCF-7/BOS breast cancer cell line.

PMID- 22138012
TI  - Estrogen-regulated synaptogenesis in the hippocampus: sexual dimorphism in vivo
      but not in vitro.
AB  - Hippocampal neurons are capable of synthesizing estradiol de novo. Estradiol
      synthesis can be suppressed by aromatase inhibitors and by knock-down of steroid
      acute regulatory protein (StAR), whereas elevated levels of substrates of
      steroidogenesis enhance estradiol synthesis. In rat hippocampal cultures, the
      expression of estrogen receptors (ERs) and synaptic proteins, as well as synapse
      density, correlated positively with aromatase activity, regardless of whether the
      cultures originated from males or females. All effects induced by the inhibition
      of aromatase activity were rescued by application of estradiol to the cultures.
      In vivo, however, systemic application of letrozole, an aromatase inhibitor,
      induced synapse loss in female rats, but not in males. Furthermore, in the female
      hippocampus, density of spines and spine synapses varied with the estrus cycle.
      In addressing this in vivo-in vitro discrepancy, we found that gonadotropin
      releasing hormone (GnRH) regulated estradiol synthesis via an aromatase-mediated
      mechanism and consistently regulated spine synapse density and the expression of
      synaptic proteins. Along these lines, GnRH receptor density was higher in the
      hippocampus than in the cortex and hypothalamus, and estrus cyclicity of
      spinogenesis was found in the hippocampus, but not in the cortex. Since GnRH
      receptor expression also varies with the estrus cycle, the sexual dimorphism in
      estrogen-regulated spine synapse density in the hippocampus very likely results
      from differences in the GnRH responsiveness of the male and the female
      hippocampus. This article is part of a Special Issue entitled 'Neurosteroids'.

PMID- 22138013
TI  - Does economic burden influence quality of life in breast cancer survivors?
AB  - GOALS: Economic burden is emerging as a crucial dimension in our understanding of
      adjustment to cancer during treatment. Yet, economic burden is rarely examined in
      cancer survivorship. The goal of this paper is to describe the effect of economic
      hardship and burden among women with breast cancer. METHODS: We examined baseline
      and follow-up (3 and 6 month) data reported by 132 stage I and II breast cancer
      survivors assigned to the Wait Control arm of the Breast Cancer Education
      Intervention (BCEI), a clinical trial of education and support interventions.
      Repeated measures models fitted with linear mixed models were used to examine
      relationships between aspects of economic burden and overall quality of life
      (QOL) scores. Structural equation models (SEM) were used to examine the
      relationship between overall economic burden and QOL. RESULTS: Nineteen economic
      events were reported. The proportion of survivors who reported increase in
      insurance premiums increased in the 6-month study period (p=.022). The proportion
      of survivors reporting change in motivation (p=.016), productivity (p=.002),
      quality of work (p=.01), days missed from work (p<.001) and sacrificing other
      things (p=.001) declined. An increase in economic events was significantly
      associated with poorer quality of life at each of the study time points.
      CONCLUSION: Economic burden of breast cancer extends into post-treatment
      survivorship. Better understanding of economic impact and managing economic
      burden may help maintain QOL.

PMID- 22138014
TI  - The origin of the unusual broad and intense visible absorption of
      tetrathiafulvalene-annulated zinc porphyrazine: a density functional theory
      study.
AB  - The vertical excitation energies of tetrathiafulvalene (TTF)-annulated zinc
      porphyrazine (ZnPzTTF) were investigated using time-dependent density functional
      theory (TDDFT) calculations and compared to the experimental UV-vis spectra. To
      examine the effects of the aza substitutions and TTF groups on the molecular
      properties, zinc complexes of porphyrin (ZnP), porphyrazine (ZnPz) and tetraTTF
      annulated porphyrin (ZnPTTF) were also selected for comparison. It was shown that
      numerous electronic transitions with TTF-to-porphyrin or porphyrazine charge
      transfer character exist and the Q band of ZnPzTTF is dominated by TTF-to
      porphyrazine charge transfer transition mixed with porphyrazine core unit itself
      except for classic porphyrazine pi->pi* transitions. The Q band of ZnPzTTF mixes
      with other configurations, which breaks down the Gouterman's classic four-orbital
      model for the spectral interpretation. The data suggest that TDDFT/SAOP performs
      best for Q and B bands of ZnPzTTF with the maximum error in excitation energy
      being 0.17 eV. The CAM-B3LYP, omegaB97XD and M06-2X calculations qualitatively
      predict that the low-lying electronic transitions of ZnPzTTF with TTF-to
      porphyrazine charge transfer character located below the Q band. The broad and
      intense red-shifted Q band suggests that ZnPzTTF can be a candidate for dye
      sensitized solar cells.

PMID- 22138015
TI  - Theoretical investigations on electronic spectra and the redox-switchable second
      order nonlinear optical responses of rhodium(I)-9,10-phenanthrenediimine
      complexes.
AB  - The redox-switchable second-order nonlinear optical (NLO) properties of a series
      of Rh(I) complexes have been studied based on density functional theory (DFT)
      calculations. The analysis of the electronic structure shows that the Rh(I) ion
      acts as the oxidation center in a one-electron-oxidized process, while both the
      Rh(I) ion and the 9,10-phenanthrenediimine (phdi) ligand act as reduction centers
      in a one-electron-reduced process. Different redox centers lead to different
      charge-transfer (CT) features, which alter the static first hyperpolarizabilities
      of the neutral complexes. Our DFT calculations indicated that these complexes
      show large second-order NLO responses and that the redox process can
      significantly enhance these NLO responses. For complexes 2 and 3, the beta(tot)
      values of the one-electron-reduced species 2(-) and the one-electron-oxidized
      species 3(+) are ~10.0 and ~8.5 times larger, respectively, than those of the
      corresponding neutral complexes. Therefore, complexes 2 and 3 are promising
      candidates for redox-switchable NLO molecular materials. The large NLO responses
      of the oxidized species are mainly related to ligand-to-ligand charge-transfer
      (LLCT) transitions when combined with intraligand charge-transfer (ILCT)
      transitions, while the results for the reduced species are strongly associated
      with metal-to-ligand charge-transfer (MLCT) transitions.

PMID- 22138016
TI  - Diversity of Nosema associated with bumblebees (Bombus spp.) from China.
AB  - Bumblebees (Bombus spp.) are important pollinators of many economically important
      crops and microsporidia are among the most important infections of these hosts.
      Using molecular markers, we screened a large sample (n=1,009 bees) of workers of
      27 different Bombus spp. from China (Sichuan, Qinghai, Inner Mongolia, and Gansu
      provinces). The results showed that 62 individuals representing 12 Bombus spp.
      were infected by microsporidia with an overall prevalence of 6.1%. Based on the
      haplotypes (ssrRNA sequences), we confirmed the presence of Nosema bombi, Nosema
      ceranae and (likely) Nosema thomsoni. In addition, four new putatively novel taxa
      were identified by phylogenetic reconstruction: Nosema A, Nosema B-complex,
      Nosema C-complex and Nosema D-complex. In many cases, hosts were infected by more
      than one Nosema taxon. Possible caveats of sequence analyses are discussed.

PMID- 22138017
TI  - Expression and strain variation of the novel "small open reading frame" (smorf)
      multigene family in Babesia bovis.
AB  - Small open reading frame (smorf) genes comprise the second largest Babesia bovis
      multigene family. All known 44 variant smorf genes are located in close
      chromosomal proximity to ves1 genes, which encode proteins that mediate
      cytoadhesion and contribute to immune evasion. In this study, we characterised
      the general topology of smorf genes and investigated the gene repertoire,
      transcriptional profile and SMORF expression in two distinct strains, T2Bo and
      Mo7. Sequence analysis using degenerate primers identified additional smorf genes
      in each strain and demonstrated that the smorf gene repertoire varies between
      strains, with conserved and unique genes in both. Smorf genes have multiple semi
      conserved and variable blocks, and a large hypervariable insertion in 20 of the
      44 genes defines two major branches of the family, termed smorf A and smorf B. A
      total of 32 smorf genes are simultaneously transcribed in T2Bo strain B. bovis
      merozoites obtained from deep brain tissue of an acutely infected animal. SMORF
      peptide-specific antiserum bound in immunoblots to multiple proteins with a range
      of sizes predicted by smorf genes, confirming translation of smorf gene products
      from these transcripts. These results indicate that the smorf multigene family is
      larger than previously described and demonstrate that smorf genes are expressed
      and are undergoing variation, both within strains and in a lineage-specific
      pattern independent of strain specificity. The function of these novel proteins
      is unknown.

PMID- 22138018
TI  - A method for rapid regulation of protein expression in Trypanosoma cruzi.
AB  - Analysis of gene function in Trypanosoma cruzi is limited due to the absence of
      rapid, simple and reversible genetic tools to regulate gene and corresponding
      protein expression. We have designed a modified pTREX vector which uses an N
      terminal fusion of a ligand-controlled destabilisation domain (ddFKBP) to a
      gene/protein of interest. This vector allows rapid and reversible protein
      expression and efficient functional analysis of proteins in different T. cruzi
      life cycle stages.

PMID- 22138019
TI  - Free radicals enzymatically triggered by Clonorchis sinensis excretory-secretory
      products cause NF-kappaB-mediated inflammation in human cholangiocarcinoma cells.
AB  - Chronic clonorchiasis, caused by direct and continuous contact with Clonorchis
      sinensis worms and their excretory-secretory products, is associated with
      hepatobiliary damage, inflammation, periductal fibrosis and even development of
      cholangiocarcinoma. Our previous report revealed that intracellular reactive
      oxygen species were generated in C. sinensis excretory-secretory product-treated
      human cholangiocarcinoma cells; however, their endogenous sources and
      pathophysiological roles in host cells were not determined. In the present study,
      we found that treatment of human cholangiocarcinoma cells with excretory
      secretory products triggered increases in free radicals via a time-dependent
      activation of NADPH oxidase, xanthine oxidase and inducible nitric oxide
      synthase. This increase in free radicals substantially promoted the degradation
      of cytosolic IkappaB-alpha, nuclear translocation of nuclear factor-kappaB
      subunits (RelA and p50), and increased kappaB consensus DNA-binding activity.
      Excretory-secretory product-induced nuclear factor-kappaB activation was markedly
      attenuated by preincubation with specific inhibitors of each free radical
      producing enzyme or the antioxidant, N-acetylcysteine. Moreover, excretory
      secretory products induced an increase in the mRNA and protein expression of the
      proinflammatory cytokines, IL-1beta and IL-6, in an nuclear factor-kappaB
      dependent manner, indicating that enzymatic production of free radicals in ESP
      treated cells participates in nuclear factor-kappaB-mediated inflammation. These
      findings provide new insights into the pathophysiological role of C. sinensis
      excretory-secretory products in host chronic inflammatory processes, which are
      initial events in hepatobiliary diseases.

PMID- 22138020
TI  - Hypothalamic pituitary adrenal axis and sympathetic activation: joint predictors
      of memory in children, adolescents, and adults.
AB  - Although the links between physiological arousal and adults' memory for emotional
      information are well understood, little is known about these links across
      development or when memory is examined for the actual event that induced arousal.
      In the current study, we examined the associations between physiological arousal
      and memory in children, adolescents, and young adults. Participants completed a
      laboratory stressor, the Trier Social Stress Test-Modified (TSST-M) during which
      salivary cortisol, pre-ejection period (PEP), and self-reported distress were
      measured. Two weeks later, participants completed a surprise memory test about
      what occurred during the TSST-M. Larger cortisol responses predicted enhanced
      memory, especially among individuals who also exhibited a PEP response the TSST
      M. These associations did not vary with age. Results have implications for
      understanding how coordinated physiological responses may influence memory for
      salient, personal experiences across development.

PMID- 22138021
TI  - How does long term exposure to base stations and mobile phones affect human
      hormone profiles?
AB  - OBJECTIVES: This study is concerned with assessing the role of exposure to radio
      frequency radiation (RFR) emitted either from mobiles or base stations and its
      relations with human's hormone profiles. DESIGN AND METHODS: All volunteers'
      samples were collected for hormonal analysis. RESULTS: This study showed
      significant decrease in volunteers' ACTH, cortisol, thyroid hormones, prolactin
      for young females, and testosterone levels. CONCLUSION: The present study
      revealed that high RFR effects on pituitary-adrenal axis.

PMID- 22138023
TI  - The signature-based radiation-scanning approach to standoff detection of
      improvised explosive devices.
AB  - The signature-based radiation-scanning technique for detection of improvised
      explosive devices is described. The technique seeks to detect nitrogen-rich
      chemical explosives present in a target. The technology compares a set of
      "signatures" obtained from a test target to a collection of "templates", sets of
      signatures for a target that contain an explosive in a specific configuration.
      Interrogation of nitrogen-rich fertilizer samples, which serve as surrogates for
      explosives, is shown experimentally to be able to discriminate samples of 3.8L
      and larger.

PMID- 22138022
TI  - Rapid simultaneous determination of voriconazole and its N-oxide in human plasma
      using an isocratic high-performance liquid chromatography method and its clinical
      application.
AB  - OBJECTIVES: The aim of this study was to develop a simultaneous determination
      method for voriconazole (VRCZ) and its N-oxide (VNO) in human plasma and to apply
      it to clinical samples. DESIGN AND METHODS: Plasma specimens were deproteinized
      with acetonitrile and then injected into an HPLC-UV system. VRCZ and VNO were
      separated on an ODS column filled with 2.3-MUm particles using an isocratic
      mixture of acetonitrile/methanol/phosphate buffer 25/10/65 (v/v/v). Plasma
      concentrations of VRCZ and VNO in 25 patients were determined. RESULTS: Both VRCZ
      and VNO were linear (r>0.999) over the concentration ranges of 0.1-8.0mg/L. The
      run time for quantification of the analytes was 4 min. Interindividual variation
      in the plasma concentration of VRCZ that ranged from less than 0.1 to 6.96 mg/L
      was observed. VNO concentrations weakly depended on VRCZ dosage. CONCLUSIONS: The
      present method can contribute to the optimization of antifungal therapy using
      VRCZ.

PMID- 22138024
TI  - Characterization of a CT ionization chamber for radiation field mapping.
AB  - A pencil-type ionization chamber, developed at Instituto de Pesquisas Energeticas
      e Nucleares (IPEN), was characterized with the objective to verify the
      possibility of its application in radiation field mapping procedures. The
      characterization tests were evaluated, and the results were satisfactory. The
      results obtained for the X radiation field mapping with the homemade chamber were
      compared with those of a PTW Farmer-type chamber (TN 30011-1). The maximum
      difference observed in this comparison was only 1.25%, showing good agreement.

PMID- 22138025
TI  - Comparison of neutron spectrum measurement methods used for the epithermal beam
      of the LVR-15 research reactor.
AB  - The LVR-15 research reactor's horizontal channel with its epithermal neutron beam
      is used mainly for boron neutron capture therapy. Neutrons from the reactor core
      pass through a special filter before the collimator and the beam outlet. Neutron
      fluence and spectrum are the basic characteristics of an epithermal neutron beam.
      Three methods used to measure the beam's neutron spectrum are described: the
      activation method, a Bonner sphere spectrometer with gold activation detectors
      and a Bonner sphere spectrometer with LiI(Eu) scintillation detector. Examples of
      results are compared and discussed.

PMID- 22138026
TI  - Multiple endocrine neoplasia type 1 presenting as refractory epilepsy and
      polyneuropathy--a case report.
AB  - Hypoglycemia is a well recognized cause of acute symptomatic seizures. The fact
      that hypoglycemia can cause peripheral neuropathy is less appreciated. We
      describe a case of insulinoma associated peripheral neuropathy. A 17 year-old
      previously healthy man was referred for investigation of refractory epilepsy. A
      history of recurrent seizures, slowly progressive weakness of his feet and hands,
      and weight gain was obtained. Physical examination showed signs of a chronic
      sensory-motor polyneuropathy. He was diagnosed with insulinoma and primary
      hyperparathyroidism, characterizing multiple endocrine neoplasia, type 1
      syndrome. Cases of insulinoma associated peripheral neuropathy are very rare. The
      more characteristic clinical picture appears to be distal weakness, worse in the
      intrinsic hand and feet muscles, and no or mild sensory signs. Peripheral nervous
      system symptoms may not completely resolve, despite removal of the cause of
      hyperinsulinism/hypoglycemia and full reversion of central nervous system
      symptoms. Mechanisms underlying hypoglycemic neuropathy are still poorly
      understood.

PMID- 22138027
TI  - Varicella zoster vs. herpes simplex meningoencephalitis in the PCR era. A single
      center study.
AB  - BACKGROUND: The introduction of polymerase chain reaction (PCR) for the diagnosis
      of herpesvirus central nervous system infections is reshaping our understanding
      of these illnesses. Varicella-zoster virus (VZV) is increasingly recognized as an
      important etiology of sporadic viral meningoencephalitis (ME). Furthermore, mild
      cases of herpes simplex virus (HSV) ME, traditionally considered a devastating
      infection, are frequently reported. METHODS: We compared the demographic and
      clinical features of patients with VZV (20) and HSV (17) ME diagnosed by Real
      Time PCR of cerebrospinal samples in a single center during the years 2002-2010.
      RESULTS: VZV and HSV patients were comparable with respect to age, sex,
      underlying diseases, immune suppression, and the rates of fever, headache and
      altered mental status on presentation. Seizures, focal neurological signs,
      systemic complications and in-hospital death were noted only in the HSV group.
      CONCLUSIONS: Our study confirms the prevalence of VZV as a cause of sporadic ME
      over the last decade. While patients with HSV ME had more manifestations of
      severe disease, there also was a significant overlap with clinical and laboratory
      parameters of VZV ME. In the absence of dermatomal rash, differentiation between
      VZV and HSV ME on clinical grounds alone may represent a true challenge.

PMID- 22138028
TI  - Sexual dimorphism of the scapula and the clavicle in a contemporary Greek
      population: applications in forensic identification.
AB  - Sex estimation is the grounds for an accurate identification of unknown human
      skeletal elements. The need for reliable methods distinguishing males from
      females based upon various skeletal elements is evident in cases of commingled,
      eroded and/or missing remains. The aim of this work lays on establishing criteria
      for sex estimation from the scapula and the clavicle in modern Greeks. A total of
      147 left scapulae and 147 clavicles (66 females and 81 males) were used in the
      study. Eight and six measurements were taken on the scapula and clavicle
      respectively and data were subjected to principal components analysis (PCA) and
      discriminant function analysis (DFA). Posterior probabilities for the
      classification of each individual are also calculated. Statistical analysis was
      carried out using the software PAST (Paleontological Statistics) and SPSS
      (Statistical Package for Social Sciences) 18. The results supported the existence
      of pronounced sexual dimorphism, which was mainly attributed to size differences
      among the two groups. Univariate and multivariate methods of statistical
      classification showed high accuracy for all scapular and most clavicular
      measurements, verifying their value as sex indicators in the under study
      population. We recommend the use of this method for sex assessment from the
      scapula and the clavicle in cases exhibiting over 95% probability of correct
      classification. This is regardless of the overall high degree of accuracy
      reported here, as the method of choice in forensic contexts should always be case
      driven.

PMID- 22138029
TI  - Seasonal structure and dynamics of sarcosaprophagous fauna on pig carrion in a
      rural area of Cordoba (Argentina): their importance in forensic science.
AB  - Four experiments, one in each season, were carried out during 2004 in a rural
      area of Cordoba, central Argentina. Two pigs (Sus scrofa L.), weighing
      approximately 8 kg each, were used in each of the four experiments. The animals
      were killed by a sharp blow to the head and immediately placed in an appropriate
      arthropod trap. One pig was placed in the shade and the other under direct
      sunlight. This research was conducted to determine the seasonal structure and
      dynamics of arthropods that constitute the sarcosaprophagous community in a given
      area of the central region of Argentina. The decomposition process was divided
      into five stages: fresh, bloated, decay, advanced decay and dry. The duration of
      each stage varied in different seasons, showing that the temperature and humidity
      are the most important variables that influence this process. A total of 51,500
      adults and 36,909 immature were collected. More than 80% of the specimens
      collected belong to Insecta, and within this, Diptera were the most abundant
      order. The flies were mainly represented by adults and immature of the following
      species: Chrysomya albiceps (Wiedemann) (Calliphoridae), Musca domestica Linnaeus
      (Muscidae) and Fannia femoralis (Stein) (Fanniidae). Coleoptera were mainly
      represented by adults and immature of the species Creophilus maxillosus
      (Linnaeus) (Staphylinidae) and Dermestes maculatus (Geer) (Dermestidae). More
      than 50% of hymenopteran fauna collected belong to Formicidae. The trophic levels
      associated with the decomposition of the remains included five categories:
      necrophagous, parasites and predators of the necrophagous species, omnivores,
      opportunists and adventives. During faunal succession a strong dominance of the
      necrophagous species of the family Calliphoridae and Muscidae was observed,
      mainly during the early stages of decay process in all seasons.

PMID- 22138030
TI  - The gastrocoel roof plate in embryos of different frogs.
AB  - The morphology of the gastrocoel roof plate and the presence of cilia in this
      structure were examined in embryos of four species of frogs. Embryos of
      Ceratophrys stolzmanni (Ceratophryidae) and Engystomops randi (Leiuperidae)
      develop rapidly, provide comparison for the analysis of gastrocoel roof plate
      development in the slow-developing embryos of Epipedobates machalilla
      (Dendrobatidae) and Gastrotheca riobambae (Hemiphractidae). Embryos of the
      analyzed frogs develop from eggs of different sizes, and display different
      reproductive and developmental strategies. In particular, dorsal convergence and
      extension and archenteron elongation begin during gastrulation in embryos of
      rapidly developing frogs, as in Xenopus laevis. In contrast, cells that involute
      during gastrulation are stored in the large circumblastoporal collar that
      develops around the closed blastopore in embryos of slow-developing frogs. Dorsal
      convergence and extension only start after blastopore closure in slow-developing
      frog embryos. However, in the neurulae, a gastrocoel roof plate develops, despite
      the accumulation of superficial mesodermal cells in the circumblastoporal collar.
      Embryos of all four species develop a ciliated gastrocoel roof plate at the
      beginning of neurulation. Accordingly, fluid-flow across the gastrocoel roof
      plate is likely the mechanism of left-right asymmetry patterning in these frogs,
      as in X. laevis and other vertebrates. A ciliated gastrocoel roof plate, with a
      likely origin as superficial mesoderm, is conserved in frogs belonging to four
      different families and with different modes of gastrulation.

PMID- 22138031
TI  - Molecular interactions of mussel protective coating protein, mcfp-1, from Mytilus
      californianus.
AB  - Protective coating of the byssus of mussels (Mytilus sp.) has been suggested as a
      new paradigm of medical coating due to its high extensibility and hardness co
      existence without their mutual detriment. The only known biomacromolecule in the
      extensible and tough coating on the byssus is mussel foot protein-1 (mfp-1),
      which is made up with positively charged residues (~20 mol%) and lack of
      negatively charged residues. Here, adhesion and molecular interaction mechanisms
      of Mytilus californianus foot protein-1 (mcfp-1) from California blue mussel were
      investigated using a surface forces apparatus (SFA) in buffer solutions of
      different ionic concentrations (0.2-0.7 M) and pHs (3.0-5.5). Strong and
      reversible cohesion between opposed positively charged mcfp-1 films was measured
      in 0.1 M sodium acetate buffer with 0.1 M KNO(3). Cohesion of mcfp-1 was
      gradually reduced with increasing the ionic strength, but was not changed with pH
      variations. Oxidation of 3,4-dihydroxyphenylalanine (DOPA) residues of mcfp-1, a
      key residue for adhesive and coating proteins of mussel, didn't change the
      cohesion strength of mcfp-1 films, but the addition of chemicals with aromatic
      groups (i.e., aspirin and 4-methylcatechol) increased the cohesion. These results
      suggest that the cohesion of mcfp-1 films is mainly mediated by cation-pi
      interactions between the positively charged residues and benzene rings of DOPA
      and other aromatic amino acids (~20 mol% of total amino acids of mcfp-1), and pi
      pi interactions between the phenyl groups in mcfp-1. The adhesion mechanism
      obtained for the mcfp-1 proteins provides important insight into the design and
      development of functional biomaterials and coatings mimicking the extensible and
      robust mussel cuticle coating.

PMID- 22138032
TI  - Cationic glycopolymers for the delivery of pDNA to human dermal fibroblasts and
      rat mesenchymal stem cells.
AB  - Progenitor and pluripotent cell types offer promise as regenerative therapies but
      transfecting these sensitive cells has proven difficult. Herein, a series of
      linear trehalose-oligoethyleneamine "click" copolymers were synthesized and
      examined for their ability to deliver plasmid DNA (pDNA) to two progenitor cell
      types, human dermal fibroblasts (HDFn) and rat mesenchymal stem cells (RMSC).
      Seven polymer vehicle analogs were synthesized in which three parameters were
      systematically varied: the number of secondary amines (4-6) within the polymer
      repeat unit (Tr4(33), Tr5(30), and Tr6(32)), the end group functionalities [PEG
      (Tr4(128)PEG-a, Tr4(118)PEG-b), triphenyl (Tr4(107)-c), or azido (Tr4(99)-d)],
      and the molecular weight (degree of polymerization of about 30 or about 100) and
      the biological efficacy of these vehicles was compared to three controls:
      Lipofectamine 2000, JetPEI, and Glycofect. The trehalose polymers were all able
      to bind and compact pDNA polyplexes, and promote pDNA uptake and gene expression
      [luciferase and enhanced green fluorescent protein (EGFP)] with these primary
      cell types and the results varied significantly depending on the polymer
      structure. Interestingly, in both cell types, Tr4(33) and Tr5(30) yielded the
      highest luciferase gene expression. However, when comparing the number of cells
      transfected with a reporter plasmid encoding enhanced green fluorescent protein,
      Tr4(33) and Tr4(107)-c yielded the highest number of HDFn cells positive for
      EGFP. Interestingly, with RMSCs, all of the higher molecular weight analogs
      (Tr4(128)PEG-a, Tr4(118)PEG-b, Tr4(107)-c, Tr4(99)-d) yielded high percentages of
      cells positive for EGFP (30-40%).

PMID- 22138034
TI  - Scavenger receptor-mediated uptake of cell-penetrating peptide nanocomplexes with
      oligonucleotides.
AB  - Cell-penetrating peptides (CPPs) are short cationic peptides that penetrate cells
      by interacting with the negatively charged plasma membrane; however, the detailed
      uptake mechanism is not clear. In contrary to the conventional mode of action of
      CPPs, we show here that a CPP, PepFect14 (PF14), forms negatively charged
      nanocomplexes with oligonucleotides and their uptake is mediated by class-A
      scavenger receptors (SCARAs). Specific inhibitory ligands of SCARAs, such as
      fucoidin, polyinosinic acid, and dextran sulfate, totally inhibit the activity of
      PF14-oligonucleotide nanocomplexes in the HeLa pLuc705 splice-correction cell
      model, while nonspecific, chemically related molecules do not. Furthermore, RNA
      interference (RNAi) knockdown of SCARA subtypes (SCARA3 and SCARA5) that are
      expressed in this cell line led to a significant reduction of the activity to
      <50%. In line with this, immunostaining shows prevalent colocalization of the
      nanocomplexes with the receptors, and electron microscopy images show no binding
      or internalization of the nanocomplexes in the presence of the inhibitory
      ligands. Interestingly, naked oligonucleotides also colocalize with SCARAs when
      used at high concentrations. These results demonstrate the involvement of SCARA3
      and SCARA5 in the uptake of PF14-oligonucleotide nanocomplexes and suggest for
      the first time that some CPP-based systems function through scavenger receptors,
      which could yield novel possibilities to understand and improve the transfection
      by CPPs.

PMID- 22138033
TI  - Selective inhibitory effect of HPMA copolymer-cyclopamine conjugate on prostate
      cancer stem cells.
AB  - Improved treatments for prostate cancer are in great need to overcome lethal
      recurrence and metastasis. Targeting the tumorigenic cancer stem cells (CSCs)
      with self-renewal and differentiation capacity appears to be a promising
      strategy. Blockade of the hedgehog (Hh) signaling pathway, an important pathway
      involved in stem cell self-renewal, by cyclopamine leads to long-term prostate
      cancer regression without recurrence, strongly suggesting the connection between
      Hh pathway and prostate CSCs. Here we designed an HPMA (N-(2
      hydroxypropyl)methacrylamide)-based cyclopamine delivery system as a CSC
      selective macromolecular therapeutics with improved drug solubility and decreased
      systemic toxicity. To this end, HPMA and N
      methacryloylglycylphenylalanylleucylglycyl thiazolidine-2-thione were
      copolymerized using the RAFT (reversible addition-fragmentation chain transfer)
      process, followed by polymer-analogous attachment of cyclopamine. The selectivity
      of the conjugate toward CSCs was evaluated on RC-92a/hTERT cells, the human
      prostate cancer epithelial cells with human telomerase reverse transcriptase
      transduction. The use of RC-92a/hTERT cells as an in vitro CSC model was
      validated by stem cell marker expression and prostasphere culture. The
      bioactivity of cyclopamine was retained after conjugation to the polymer.
      Furthermore, HPMA polymer-conjugated cyclopamine showed anti-CSC efficacy on RC
      92a/hTERT cells as evaluated by decreased stem cell marker expression and CSC
      viability.

PMID- 22138035
TI  - First inducible transgene expression in porcine large animal models.
AB  - The purpose of this study was to establish inducible transgene expression in
      pigs, a model organism with great promise for experimental physiology and
      translational medicine, using the binary tet-on system. This expression system is
      activated by doxycycline (dox) via the tet-controlled transactivator (TA).
      Binding of TA to the transactivator response element (TRE) results in
      transcription of downstream genes. First, we cloned transgenic founder pigs
      expressing TA under the control of the CMV enhancer/chicken beta-actin promoter
      (CAG). Then, cells from CAG-TA transgenic founders were nucleofected with TRE
      controlled expression vectors for either porcine cytotoxic T-lymphocyte
      associated antigen 4-Fc domain of immunoglobulin G1 (CTLA-4Ig) or soluble
      receptor activator of NF-kappaB ligand (RANKL), and double-transgenic offspring
      were cloned. Dox administration resulted in a dose-dependent increase in
      expression of CTLA-4Ig or RANKL, in nucleofected cells and in transgenic pigs,
      while in the absence of dox, the levels of both proteins were below the detection
      limit. Inducible transgene expression was reproduced in double-transgenic
      offspring generated by cloning or breeding. Our strategy revealed the first two
      examples of inducible transgene expression in pigs. The CAG-TA transgenic pigs
      generated in this study constitute an interesting basis for future pig models
      with inducible transgene expression.

PMID- 22138036
TI  - Results of a surgical resection for patients with stage IV non--small-cell lung
      cancer.
AB  - PURPOSE: This study retrospectively investigated the clinical significance of
      surgical treatment for stage IV non-small-cell lung cancer (NSCLC). SUBJECTS:
      There were 36 patients who underwent surgical resection for stage IV NSCLC
      between 1999 and 2008. RESULTS: The patients included 22 males and 14 females.
      All patients had either synchronous distant metastasis or pleural dissemination.
      The mean age of the patients was 65.8 years (range, 18 to 90 years). The
      histological types included 29 adenocarcinomas, 5 squamous-cell carcinomas and 2
      large-cell carcinomas. The organs of metastasis were bone in 5 patients, brain in
      4, adrenal gland in 4, axillary lymph nodes in 3, liver in 2, and 1 patient had a
      contralateral pulmonary metastasis. The number of metastases was one site in 13,
      two sites in 3, three sites in 1, and five sites in 2 patients. The patients with
      bone metastasis were treated with radiation, and the patients with brain
      metastasis underwent stereotaxic radiosurgery. The patients with either adrenal
      metastasis, axillary lymph node metastasis, or contralateral lung metastasis
      underwent surgical resection. Among the patients with distant metastasis, the 5
      year survival rate was 30.1 %. There were 17 patients with pleural dissemination.
      The 5-year survival rate in these patients was 25.3%. The overall 5-year survival
      rate after surgery in the patients with stage IV disease was 26.8%. CONCLUSION:
      Selected patients who can undergo surgical resection for the primary tumor and
      effective local therapy for metastatic lesions still have a chance to obtain long
      term survival. Surgical treatment for NSCLC with oligometastatic disease can be
      considered as one arm of multidisciplinary treatment.

PMID- 22138037
TI  - A randomized phase III trial of combined paclitaxel, carboplatin, and radiation
      therapy followed by weekly paclitaxel or observation for patients with locally
      advanced inoperable non-small-cell lung cancer.
AB  - BACKGROUND: This study was designed to determine the efficacy and safety of
      additional maintenance chemotherapy after standard induction
      chemotherapy/radiation therapy (XRT) in stage III non-small-cell lung cancer
      (NSCLC). The primary objective was to increase 1-year survival. PATIENTS AND
      METHODS: Eligible patients (N = 220) had confirmed stage IIIA or IIIB NSCLC, and
      an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Patients
      received induction chemotherapy (paclitaxel 200 mg/m(2) + carboplatin AUC = 6/3
      weeks) for 2 cycles, followed by paclitaxel 45 mg/m(2) + carboplatin AUC = 2
      weekly *7 and concurrent daily XRT (cumulative dose = 66.6 Gy in 37 fractions)
      and then observation or maintenance. Before randomization, 101 patients (46%)
      discontinued treatment due to progressive disease (n = 34), toxicity (n = 33),
      patient request (n = 13), death (n = 7), or other (n = 14). The remaining 119
      patients were randomly assigned to either "observation" or "maintenance" (6
      cycles of paclitaxel 70 mg/m(2)/wk [3 weeks on/1 week off]); a median of 5 of 6
      planned cycles was delivered in the maintenance arm. RESULTS: For the observation
      group vs. the maintenance group, the estimated 1- and 4-year survival rates were
      77% vs. 66% and 38% vs. 17% (median, 26.9 months vs. 16.1 months, respectively [P
      = .07]); the estimated 1- and 4-year performance-free survival (PFS) were 46% vs.
      24% and 25% vs. 13% (median, 10.2 months vs. 8.2 months, respectively [P = .04]).
      Common toxicities were neutropenia, thrombocytopenia, and fatigue. CONCLUSION:
      Median survival in both groups surpassed the standard, most notably the 26.9
      month survival in the observation group. Maintenance chemotherapy, when added to
      a regimen of both induction and concurrent chemoradiotherapy, did not improve
      clinical outcomes, with endpoints favoring the standard arm.

PMID- 22138038
TI  - Characterization of melanoma-associated antigen-a genes family differential
      expression in non-small-cell lung cancers.
AB  - BACKGROUND: The melanoma-associated antigen (MAGE) genes families are found in
      different cancers, including non-small-cell lung cancers. These genes are silent
      in normal tissues, except for the testis. The goal of this study was to
      investigate the differentially expressed profile of the different MAGE genes
      subclass in non-small-cell lung cancer (NSCLC) tumoral tissue. METHODS: Formalin
      fixed paraffin embedded NSCLC resected tissues were collected from 31 patients
      hospitalized in our referral hospital, and 29 patients were diagnosed with either
      squamous cell carcinoma (SCC) or adenocarcinoma (ADC). We used a nested reverse
      transcriptase-polymerase chain reaction, which comprised independent
      amplification of MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, and MAGE-A12, to detect
      expression frequency of the MAGE-A family in lung tissue biopsies at both tumoral
      and nontumoral parts of patients' tissues. RESULTS: From 29 patients with
      diagnosis of either SCC (n = 16) or ADCs (n = 13), 58 samples were prepared. From
      58 blocks sampled for this experiment, 37 tumoral tissue samples and 22
      nontumoral tissue samples expressed at least one of the MAGE-A genes. MAGE-A4
      gene had the highest incidence among all MAGE-A genes in both tumoral and
      nontumoral gens. In SCC and ADCs, the data showed expression of at least one of
      the MAGE-A genes in 59.4% and 69.2% of tumoral and nontumoral tissues,
      respectively. CONCLUSION: The detection of the MAGE-A genes expression could be a
      molecular tumor marker for early diagnosis and potential targets for active
      immunotherapy in NSCLC, particularly in ADCs and SCC. Besides, the frequency of
      different subtypes of MAGE genes may vary in different regions of world.

PMID- 22138040
TI  - Early life financial adversity and respiratory function in midlife: a prospective
      birth cohort study.
AB  - Data from the 1958 National Child Development Study (1958-2004) were used in a
      prospective study of the relation of financial adversity in childhood to lung
      function in midlife. It was hypothesized that such a relation would be found and
      would be mediated partly by early housing deprivation, partly by continuities in
      social disadvantage, and partly by smoking. These hypotheses were confirmed. The
      mediating variables explained nearly two-thirds of the observed relation. The
      strongest individual pathway from early financial hardship to adult lung function
      was through poor housing in childhood. Poor housing increased the risk of
      educational failure, which in turn was strongly related to less-advantaged social
      class. Lack of educational qualifications and less-advantaged social class
      independently increased the risk of higher levels of smoking. Mediating variables
      therefore acted in part as indicators of environmental exposures and in part
      through their links to adult smoking. Early financial adversity is associated
      with adult lung function partly through poor housing and partly through pathways
      involving continuities in social disadvantage and the associated environmental
      exposures and behaviors.

PMID- 22138039
TI  - Distinguishing 6 population subgroups by timing and characteristics of the
      menopausal transition.
AB  - Changes in women's menstrual bleeding patterns precede the onset of menopause. In
      this paper, the authors identify population subgroups based on menstrual
      characteristics of the menopausal transition experience. Using the TREMIN data
      set (1943-1979), the authors apply a bayesian change-point model with 8
      parameters for each woman that summarize change in menstrual bleeding patterns
      during the menopausal transition. The authors then use estimates from this model
      to classify menstrual patterns into subgroups using a K-medoids algorithm. They
      identify 6 subgroups of women whose transition experience can be distinguished by
      age at onset, variability of the menstrual cycle, and duration of the early
      transition. These results suggest that for most women, mean and variance change
      points are well aligned with proposed bleeding markers of the menopausal
      transition, but for some women they are not clearly associated. Increasing
      understanding of population differences in the transition experience may lead to
      new insights into ovarian aging. Because of age inclusion criteria, most
      longitudinal studies of the menopausal transition probably include only a subset
      of the 6 subgroups of women identified in this paper, suggesting a potential bias
      in the understanding of both the menopausal transition and the linkage between
      the transition and chronic disease.

PMID- 22138041
TI  - Brain natriuretic peptide induces CD8+ T cell death via a caspase 3 associated
      pathway--implications following heart transplantation.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) remains elevated after cardiac
      transplantation despite replacement of the failing ventricle. Serum peaks are
      also seen during acute rejection episodes independent of intracardiac hemodynamic
      disturbance. High BNP levels are also reported during bacterial sepsis, burns,
      stroke and myocardial infarction. Given all of these conditions are linked by
      immune activation processes, we hypothesised that BNP is an immunoactive agent.
      METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from whole
      blood of 40 cardiac transplant recipients. Cells were co-cultured for 72h in the
      presence or absence of BNP. Cells were then immunophenotyped using flow
      cytometry. Cell death pathways were determined using caspase 3 quantification and
      mitochondrial membrane assessment. Supernatants were analysed for cytokine,
      chemokine and growth factor production using luminex. RESULTS: Co-culture of CD8+
      T cells with BNP reduced cell number, and increased intracellular caspase 3.
      Supernatant analysis revealed that BNP reduced the expression of inflammatory
      cytokines including TNF-alpha, IL-1alpha and IL-6. However it preserved the
      production of anti-inflammatory and regulatory cytokines such as IL-4, 5 and 13.
      CONCLUSION: Our findings provide evidence that BNP directly induces CD8+ T cell
      apoptosis via a caspase 3 associated mechanism from cardiac transplant patients.
      This may impart significant consequences on immune mediated disease processes,
      such as allograft rejection.

PMID- 22138042
TI  - Robust two-gene classifiers for cancer prediction.
AB  - Two-gene classifiers have attracted a broad interest for their simplicity and
      practicality. Most existing two-gene classification algorithms were involved in
      exhaustive search that led to their low time-efficiencies. In this study, we
      proposed two new two-gene classification algorithms which used simple univariate
      gene selection strategy and constructed simple classification rules based on
      optimal cut-points for two genes selected. We detected the optimal cut-point with
      the information entropy principle. We applied the two-gene classification models
      to eleven cancer gene expression datasets and compared their classification
      performance to that of some established two-gene classification models like the
      top-scoring pairs model and the greedy pairs model, as well as standard methods
      including Diagonal Linear Discriminant Analysis, k-Nearest Neighbor, Support
      Vector Machine and Random Forest. These comparisons indicated that the
      performance of our two-gene classifiers was comparable to or better than that of
      compared models.

PMID- 22138043
TI  - Mineral-microbe interactions: biotechnological potential of bioweathering.
AB  - Mineral-microbe interaction has been a key factor shaping the lithosphere of our
      planet since the Precambrian. Detailed investigation has been mainly focused on
      the role of bioweathering in biomining processes, leading to the selection of
      highly efficient microbial inoculants for the recovery of metals. Here we expand
      this scenario, presenting additional applications of bacteria and fungi in
      mineral dissolution, a process with novel biotechnological potential that has
      been poorly investigated. The ability of microorganisms to trigger soil formation
      and to sustain plant establishment and growth are suggested as invaluable tools
      to counteract the expansion of arid lands and to increase crop productivity.
      Furthermore, interesting exploitations of mineral weathering microbes are
      represented by biorestoration and bioremediation technologies, innovative and
      competitive solutions characterized by economical and environmental advantages.
      Overall, in the future the study and application of the metabolic properties of
      microbial communities capable of weathering can represent a driving force in the
      expanding sector of environmental biotechnology.

PMID- 22138044
TI  - Targeting c-Met as a promising strategy for the treatment of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a severe condition that is found worldwide.
      Liver transplantation, surgical resection, and local-regional therapy such as
      transarterial chemoembolization have made great progress and play a dominant role
      in HCC management. However, the high frequency of tumor recurrence and/or
      metastasis after those treatments acquires systematic drug intervention. The
      approval of sorafenib, an agent that targets receptor tyrosine kinases (RTKs), as
      the first effective drug for systemic treatment of HCC represents a milestone in
      treatment of this disease. As a typical member of the RTK family, c-Met
      represents an intriguing target for cancer therapy. However, the role of the c
      Met signal transduction pathway is less unambiguous in HCC pathology, giving rise
      to concerns about the feasibility of utilizing c-Met targeting approaches for HCC
      treatment. Recently, studies on des-gamma-carboxy prothrombin, an abnormal
      cytokine secreted by HCC cells, by the current authors and other researchers have
      highlighted the critical role of c-Met signaling in HCC progression. This review
      takes a second look at the c-Met signal transduction pathway and discusses the
      possibility of targeting c-Met as a therapeutic strategy for HCC treatment.

PMID- 22138045
TI  - Still not enough taxonomists: reply to Joppa et al.

PMID- 22138046
TI  - Asymmetry of lexico-semantic processing in schizophrenia changes with disease
      progression.
AB  - BACKGROUND: Are anomalies of cerebral asymmetry integral to the disease process?
      Here, we examined the influence of age, chronicity and age of onset of illness in
      34 patients with early onset schizophrenia and 20 controls in relation to
      structural asymmetries of the temporal lobe and performance asymmetries on a
      semantic language lexical decision task. METHODS: Volumetric MRI and a novel
      divided visual field probe of lateralised lexico-semantic language were assessed
      in patients with early onset schizophrenia (EOS) and controls. Novel ratios of
      age-illness overlap and directional asymmetry were developed in order to examine
      the association of chronicity factors to asymmetry. RESULTS: Loss of laterality
      on the lexical decision task and discordant structural asymmetry were correlated
      with duration of illness but were not seen in younger, less chronic patients.
      Reduced lateral processing speed, and discordant structural asymmetry were
      associated with greater proportion of lifetime schizophrenia. CONCLUSION:
      Although the conclusions are limited by the cross sectional nature of the study,
      anomalies of cerebral asymmetry in early onset patients may be an index of
      disease progression, and reflect directly on the disease process.

PMID- 22138047
TI  - Are there specific neuropsychological deficits underlying poor insight in first
      episode psychosis?
AB  - Insight in psychosis is a multi-dimensional phenomenon, and has been hypothesised
      to have some sort of neuropsychological basis. It is unclear to what extent
      specific neuropsychological abilities are able to predict insight beyond the
      effect of generalised cognitive ability. We aimed to test this association,
      alongside the relationship of insight with illness duration and diagnosis, in a
      sample of first episode psychosis patients. 110 first episode psychosis patients
      were recruited and a comprehensive assessment was administered, including
      insight, symptoms, diagnosis and neuropsychological function. Low insight was
      related to worse performance in a variety of neuropsychological tasks. Regression
      analysis tested whether any specific tasks were related to insight (or dimensions
      of insight) beyond the effect of IQ. Verbal memory had an effect on total insight
      and all dimensions of insight (except compliance) beyond the effect of IQ.
      Insight appeared to vary with diagnosis, with those diagnosed with depressive
      affective psychoses having better insight than those with manic affective
      psychoses. There was no relationship between insight and DUP, but there was a
      relationship between time spent in treatment before assessment and insight, even
      after controlling for severity of symptoms. These results suggest a model of
      insight in early psychosis with a significant neuropsychological component,
      particularly with verbal memory but also with generalised cognitive ability.
      There is likely to be a social component to insight affected by initial time
      spent in contact with treatment, helping patients to understand and come to terms
      with their illness.

PMID- 22138049
TI  - Genetic and functional analysis of the gene encoding GAP-43 in schizophrenia.
AB  - OBJECTIVES: In earlier reports, growth-associated protein 43 (GAP-43) has been
      shown to be critical for initial establishment or reorganization of synaptic
      connections, a process thought to be disrupted in schizophrenia. Additionally,
      abnormal GAP-43 expression in different brain regions has been linked to this
      disorder in postmortem brain studies. In this study, we investigated the
      involvement of the gene encoding GAP-43 in the susceptibility to schizophrenia.
      METHODS: We searched for genetic variants in the promoter region and 3 exons
      (including both UTR ends) of the GAP-43 gene using direct sequencing in a sample
      of patients with schizophrenia (n=586) and non-psychotic controls (n=576), both
      being Han Chinese from Taiwan, and conducted an association and functional study.
      RESULTS: We identified 11 common polymorphisms in the GAP-43 gene. SNP and
      haplotype-based analyses displayed no associations with schizophrenia.
      Additionally, we identified 4 rare variants in 5 out of 586 patients, including 1
      variant located at the promoter region (c.-258-4722G>T) and 1 synonymous (V110V)
      and 2 missense (G150R and P188L) variants located at exon 2. No rare variants
      were found in the control subjects. The results of the reporter gene assay
      demonstrated that the regulatory activity of construct containing c.-258-4722T
      was significantly lower as compared to the wild type construct (c.-258-4722G;
      p<0.001). In silico analysis also demonstrated the functional relevance of other
      rare variants. CONCLUSIONS: Our study lends support to the hypothesis of multiple
      rare mutations in schizophrenia, and it provides genetic clues that indicate the
      involvement of GAP-43 in this disorder.

PMID- 22138048
TI  - Sensorimotor gating and clinical outcome following cognitive behaviour therapy
      for psychosis.
AB  - BACKGROUND: Prepulse inhibition (PPI) of the startle response refers to the
      ability of a weak prestimulus to transiently inhibit the response to a closely
      following strong sensory stimulus. PPI provides an operational index of
      sensorimotor gating and is reduced, on average, in people with schizophrenia,
      relative to healthy people. Given the variable response to Cognitive Behaviour
      Therapy for psychosis (CBTp) and positive associations between pre-therapy brain
      and cognitive functions and CBT outcome across disorders, we examined whether pre
      therapy level of PPI is associated with clinical outcome following CBTp. METHOD:
      Fifty-six outpatients stable on medication with at least one distressing symptom
      of schizophrenia and willing to receive CBTp in addition to their usual treatment
      were assessed on acoustic PPI. Subsequently, 28 patients received CBTp
      (CBTp+treatment-as-usual, 23 completers) for 6-8months and 28 continued with
      their treatment-as-usual (TAU-alone, 17 completers). Symptoms were assessed
      (blindly) at entry and follow-up. RESULTS: The CBTp+TAU and TAU-alone groups did
      not differ demographically, clinically or in PPI at baseline. The CBTp+TAU group
      showed improved symptoms relative to the TAU-alone group, which showed no change,
      at follow-up. Pre-therapy PPI level correlated positively with post-CBTp symptom
      improvement. CONCLUSIONS: Relatively intact sensorimotor gating is associated
      with a good clinical response following a 6-8months course of NICE compliant CBTp
      in schizophrenia. Pharmacological or psychological interventions capable of
      improving PPI may enhance the effectiveness of CBTp in people with schizophrenia,
      particularly in those who fail to show clinical improvement with currently
      available antipsychotic drugs and adjunctive CBTp.

PMID- 22138050
TI  - Interactive effects of background facial emotion stimulus and target salience on
      sustained attention performance in schizophrenia.
AB  - Schizophrenia impairs both facial emotion processing and sustained attention.
      Through separate studies, it is known that the presence of a task-irrelevant
      facial stimulus disproportionately interferes with performance, whereas
      increasing the salience of task stimulus improves performance during a sustained
      attention task in patients with schizophrenia. We wished to investigate a
      potential interaction effect of background facial emotion expression (black and
      white happy faces vs. grey oval) and target stimulus salience (bright white vs.
      grey) using the Continuous Performance Test-Identical Pairs version (CPT-IP) in
      patients with schizophrenia. Thirty-six patients with schizophrenia and 28
      healthy control subjects completed 4 different versions of the CPT-IP. We found
      that healthy controls exhibited higher signal detection sensitivity (d') when
      salient target stimuli were presented on the facial background than when the same
      stimuli were presented on the grey-oval background. By contrast, patients were
      not affected by background stimuli when target number stimuli were salient. When
      target number stimuli were not salient, both patients and controls showed higher
      d' in the grey-oval background condition compared with the facial background
      condition. This study highlight the significance of stimulus salience during CPT
      IP in schizophrenia as background stimuli did not produce a differential effect
      on performance. Our results suggest that, in the situations where facial emotion
      stimuli are present, patients' sustained attention can be deteriorated and that
      the use of salient materials is important in improving performance in
      schizophrenia.

PMID- 22138051
TI  - Regional differences and temporal trends in male reproductive health disorders:
      semen quality may be a sensitive marker of environmental exposures.
AB  - The decline in semen quality has been the subject of an animated debate. A recent
      prospective study now irrefutably shows a decline in semen quality in men from
      Finland, a country that previously boasted good semen quality. Semen quality has,
      in some countries, reached a level where a considerable fraction of young men are
      at risk of fertility problems. Impaired semen quality, testicular cancer,
      cryptorchidism and hypospadias are risk factors for each other, and the
      testicular dysgenesis syndrome (TDS) has been put forward to explain the
      observations. This syndrome implies that the four disease entities share the same
      patho-physiological etiology caused by disturbed testicular development in early
      fetal life. It seems likely that the rapid rise in TDS-associated conditions can,
      at least partly, be explained by environmental factors. Animal studies provide
      strong evidence that manmade chemicals can disrupt the hormone dependent pathways
      responsible for fetal gonadal development, subsequently leading to TDS-like
      symptoms. In humans, fetal exposure to endocrine disrupting substances may play a
      role, although genetic factors are probably also involved. Recent studies
      indicate that exposure to endocrine disrupters also in adulthood may affect semen
      quality and reproductive hormones. Causal relationships are inherently difficult
      to establish in humans, and a clear connection between the disorders and specific
      toxicants has not been established. It seems likely that the cumulative effects
      of various low-dose exposures to endocrine disrupters in our environment are
      responsible for the adverse effects in the male reproductive system. Semen
      quality may be the most sensitive marker of adverse environmental exposures, and
      we suggest that standardized surveillance studies of semen quality are continued
      or initiated to monitor the combined effects of various preventive actions.

PMID- 22138052
TI  - CCK receptors-related signaling involved in nitric oxide production caused by
      gastrin 17 in porcine coronary endothelial cells.
AB  - In anesthetized pigs gastrin-17 increased coronary blood flow through CCK1/CCK2
      receptors and beta(2)-adrenoceptors-related nitric oxide (NO) release. Since the
      intracellular pathway has not been investigated the purpose of this study was to
      examine in coronary endothelial cells the CCK1/CCK2 receptors-related signaling
      involved in the effects of gastrin-17 on NO release. Gastrin-17 caused a
      concentration-dependent increase of NO production (17.3-62.6%; p<0.05), which was
      augmented by CCK1/CCK2 receptors agonists (p<0.05). The effect of gastrin-17 was
      amplified by the adenylyl-cyclase activator and beta(2)-adrenoceptors agonist
      (p<0.05), abolished by cAMP/PKA and beta(2)-adrenoceptors and CCK1/CCK2 receptors
      blockers, and reduced by PLC/PKC inhibitor. Finally, Western-blot revealed the
      preferential involvement of PKA vs. PKC as downstream effectors of CCK1/CCK2
      receptors activation leading to Akt, ERK, p38 and endothelial NOS (eNOS)
      phosphorylation. In conclusion, in coronary endothelial cells, gastrin-17 induced
      eNOS-dependent NO production through CCK1/CCK2 receptors- and beta(2)
      adrenoceptors-related pathway. The intracellular signaling involved a
      preferential PKA pathway over PKC.

PMID- 22138053
TI  - Fruitless RNAi knockdown in the desert locust, Schistocerca gregaria, influences
      male fertility.
AB  - In Drosophila melanogaster, the male-specific splice isoform of the fruitless
      gene (Fru(M)) encodes a set of transcription factors that are involved in the
      regulation of male courtship and copulation. Recent insights from non-drosophilid
      insects suggest a conserved evolutionary role for the transcription factor
      Fruitless. In the desert locust, Schistocerca gregaria and the German cockroach,
      Blatella germanica, both orthopteran insects, a conserved functional role for
      fruitless has been proposed. Fru specific RNAi knockdown in the third nymphal
      stage of male Schistocera gregaria delays copulation initiation and results in
      reduced progeny. In order to identify the origin of the observed phenotypic
      effects following a fruitless RNAi treatment in the male, we show that the fru
      knockdown has no detectable effect on spermio- or spermatogenesis and on the
      transfer of spermatozoa during copulation. Nevertheless, it is clear that the
      male seminal vesicles contain significantly less spermatozoa after fru RNAi as
      compared to gfp RNAi controls. We conclude that a lowered male fertility, caused
      by the fru knockdown in male desert locusts may be the direct cause for the
      reduction of the progeny numbers in their naive female copulation partners.

PMID- 22138054
TI  - Foreword to this special edition of the Journal of Insect Physiology.

PMID- 22138056
TI  - Dgcr8 controls neural crest cells survival in cardiovascular development.
AB  - DiGeorge syndrome (DGS), characterized genetically by a deletion within
      chromosome 22q11.2, is associated with a constellation of congenital heart
      defects. DiGeorge critical region 8 (Dgcr8), a gene that maps to the common
      deletion region of DGS, encodes a double stranded RNA-binding protein that is
      essential for miRNA biogenesis. To address the potential contribution of Dgcr8
      insufficiency to cardiovascular development, we have inactivated Dgcr8 in cardiac
      neural crest cells (cNCCs). Dgcr8 mutants displayed a wide spectrum of
      malformations, including persistent truncus arteriosus (PTA) and ventricular
      septal defect (VSD). Interestingly, Dgcr8-null cNCCs that properly migrated into
      the cardiac outflow tract (OFT), proliferate normally and differentiate into
      vascular smooth muscle cells. However, loss of Dgcr8 causes a significant portion
      of the cNCCs to undergo apoptosis, causing a decrease in the pool of progenitors
      required for OFT remodeling. Our data uncover a new role of Dgcr8 in
      cardiovascular morphogenesis, plausibly as part of transmission mechanism for FGF
      dependent survival cue for migrating cNCCs.

PMID- 22138055
TI  - Some, but not all, retromer components promote morphogenesis of C. elegans
      sensory compartments.
AB  - The endings of sensory receptor cells often lie within specialized compartments
      formed by glial cells. The main sensory organ of Caenorhabditis elegans, the
      amphid, provides a powerful setting for studying glial compartment morphogenesis.
      Our previous studies showed that amphid compartment size is controlled by
      opposing activities of the Nemo-like kinase LIT-1, which promotes compartment
      expansion, and the Patched-related protein DAF-6, which restricts compartment
      growth. From a genetic screen for mutations able to suppress the bloated sensory
      compartments of daf-6 mutants, we identified an allele of the sorting nexin gene
      snx-1. SNX-1 protein is a component of the retromer, a protein complex that
      facilitates recycling of transmembrane proteins from the endosome to the Golgi
      network. We find that snx-1 functions cell autonomously within glia to promote
      sensory compartment growth, and that SNX-1 protein is enriched near the surface
      of the sensory compartment. snx-1 interacts genetically with lit-1 and another
      regulator of compartment size, the Dispatched-related gene che-14. Mutations in
      snx-3 and vps-29, also retromer genes, can suppress daf-6 defects. Surprisingly,
      however, remaining retromer components seem not to be involved. Our results
      suggest that a novel assembly of retromer components is important for determining
      sensory compartment dimensions.

PMID- 22138057
TI  - The beneficial effect of mild therapeutic hypothermia depends on the time of
      complete circulatory standstill in patients with cardiac arrest.
AB  - AIM: Mild therapeutic hypothermia has shown to improve long-time survival as well
      as favorable functional outcome after cardiac arrest. Animal models suggest that
      ischemic durations beyond 8 min results in progressively worse neurologic
      deficits. Based on these considerations, it would be obvious that cardiac arrest
      survivors would benefit most from mild therapeutic hypothermia if they have
      reached a complete circulatory standstill of more than 8 min. METHODS: In this
      retrospective cohort study we included cardiac arrest survivors of 18 years of
      age or older suffering a witnessed out-of-hospital cardiac arrest, which remain
      comatose after restoration of spontaneous circulation. Data were collected from
      1992 to 2010. We investigated the interaction of 'no-flow' time on the
      association between post arrest mild therapeutic hypothermia and good
      neurological outcome. 'No-flow' time was categorized into time quartiles (0, 1-2,
      3-8, >8 min). RESULTS: One thousand-two-hundred patients were analyzed.
      Hypothermia was induced in 598 patients. In spite of showing a statistically
      significant improvement in favorable neurologic outcome in all patients treated
      with mild therapeutic hypothermia (odds ratio [OR]: 1.49; 95% confidence interval
      [CI]: 1.14-1.93) this effect varies with 'no-flow' time. The effect is
      significant in patients with 'no-flow' times of more than 2 min (OR: 2.72; CI:
      1.35-5.48) with the maximum benefit in those with 'no-flow' times beyond 8 min
      (OR: 6.15; CI: 2.23-16.99). CONCLUSION: The beneficial effect of mild therapeutic
      hypothermia increases with cumulative time of complete circulatory standstill in
      patients with witnessed out-of-hospital cardiac arrest.

PMID- 22138058
TI  - Ultrasonographic lung sliding sign in confirming proper endotracheal intubation
      during emergency intubation.
AB  - AIM OF STUDY: Unrecognized one-lung intubations (also known as main-stem
      intubation) can lead to hypoventilation, atelectasis, barotrauma, and even
      patient death. Many traditional methods can be employed to detect one-lung
      intubation; however, each of these methods has limitations and is not
      consistently reliable in emergency settings. This study aimed to assess the
      accuracy and timeliness of ultrasound to confirm proper endotracheal intubation.
      METHODS: This was a prospective, single-center, observational study conducted at
      the emergency department of a national university teaching hospital. Patients
      received emergency tracheal intubation because of respiratory failure or cardiac
      arrest. After intubation, bedside ultrasound was performed with a transducer
      placed on the chest bilaterally at the mid-axillary line, to identify lung
      sliding over the lungs bilaterally during ventilation. Chest radiography was used
      as the criterion standard for confirmation of endotracheal tube position.
      RESULTS: One hundred and fifteen patients needing tracheal intubation were
      included, and nine (7.8%) had one-lung intubations. The overall accuracy of
      ultrasound to confirm proper endotracheal intubation was 88.7% (95% confidence
      interval (CI): 81.6-93.3%). The positive predictive value was 94.7% (95% CI: 87.1
      97.9%) in the non-cardiac-arrest group and 100% (95% CI: 87.1-100.0%) in the
      cardiac-arrest group. The median operating time of ultrasound was 88 s
      (interquartile range [IQR]: 55.0, 193.0), and of chest radiography was 1349 s
      (IQR: 879.0, 2221.0) post intubation. CONCLUSIONS: In this study, the positive
      predictive value of bilateral lung sliding in confirming proper endotracheal
      intubation was high, especially among patients with cardiac arrest. Considerable
      time advantage of ultrasound over chest radiography was demonstrated.

PMID- 22138059
TI  - Not all sarcomas developed in irradiated tissue are necessarily radiation-induced
      -spectrum of disease and treatment characteristics.
AB  - BACKGROUND: Sarcomas in irradiated tissue (SITs) are often considered with second
      cancers, although they usually present distinct dose-response, genetic and
      clinical patterns. The contribution of radiation in SIT development is likely,
      but remains unproven in many cases. MATERIALS AND METHODS: We reviewed the
      literature for published data on SITs. RESULTS: SITs incidence ranged between
      0.03% and 0.2%. Median latency was 15 years. Angiosarcoma was the second most
      common subtype after undifferentiated sarcomas of malignant fibrous histiocytoma
      (MFH). C-Myc overexpression can be used to identify radiation-induced
      angiosarcoma, and a recently described transcriptomic signature of genes involved
      in chronic oxidative stress and mitochondrial dysfunction may indicate radiation
      causality. Osteosarcomas were often associated with genetic predisposition. Five
      year survival rates rarely exceeded 30% because the therapeutic possibilities
      were often limited by the first cancer. Chemotherapy response may differ from
      that of de novo sarcomas. CONCLUSION: SITs present different characteristics from
      non-sarcomatoid second cancers. Reporting of SIT cases and the establishment of
      tissue and serum banks is necessary to better understand and validate the
      recently discovered radiation signature.

PMID- 22138061
TI  - Gastric mucormycosis: a rare cause of gastrointestinal bleeding in cirrhosis.

PMID- 22138060
TI  - Review: Human trophoblast fusion and differentiation: lessons from trisomy 21
      placenta.
AB  - The syncytiotrophoblast layer plays a major role throughout pregnancy, since it
      is the site of numerous placental functions, including ion and nutrient exchange
      and the synthesis of steroid and peptide hormones required for fetal growth and
      development. Inadequate formation and regeneration of this tissue contributes to
      several pathologies of pregnancy such as intrauterine growth restriction and
      preeclampsia, which may lead to iatrogenic preterm delivery in order to prevent
      fetal death and maternal complications. Syncytiotrophoblast formation can be
      reproduced in vitro using different models. For the last ten years we have
      routinely purified villous cytotrophoblastic cells (CT) from normal first, second
      and third trimester placentas and from gestational age-matched Trisomy 21
      placentas. We cultured villous CT on plastic dishes to follow the molecular and
      biochemical aspects of their morphological and functional differentiation. Taking
      advantage of this unique collection of samples, we here discuss the concept that
      trophoblast fusion and functional differentiation may be two differentially
      regulated processes, which are linked but quite distinct. We highlight the major
      role of mesenchymal-trophoblast cross talk in regulating trophoblast cell fusion.
      We suggest that the oxidative status of the trophoblast may regulate
      glycosylation of proteins, including hCG, and thereby modulate major trophoblast
      cell functions.

PMID- 22138062
TI  - Have French recommendations had an impact on the treatment and survival of middle
      and lower rectal cancer patients?
AB  - OBJECTIVE: Compare the survival of middle and lower rectal cancer (MLRC) patients
      before and after the 1994 issue of rectal cancer (RC) consensus conference
      recommendations. METHODS: Cases of MLRC noted in the Herault department of France
      in 1992 (n=58) and 2000 (n=93) yielded exhaustive epidemiological, clinical
      pathological and treatment data that were used to compare MLRC patient management
      and survival in these two periods. RESULTS: Significantly more lymph nodes (>= 8)
      were harvested in 2000 (>= 8, 47%) than in 1992. In all, 45 patients (77.6%)
      received radiotherapy in 1992, and 74 (82%) in 2000. Chemotherapy was employed in
      15 patients (25.9%) in 1992 and in 39 patients (43%) in 2000. Chemotherapy and
      radiotherapy, together with sphincter conservation, were dependent upon the year.
      Overall 5-year relative survival for rectal cancer in the Herault department did
      not vary between 1992 (56%) and 2000 (56%). Independent poor prognostic factors
      were the same in both years: age over 75 years, lymph node involvement and
      metastases. Management place and year had no significant impact on prognosis.
      CONCLUSION: The recommendations made have had little impact on disease management
      and the quality of anatomic pathology reports, and have not improved 5-year
      relative survival.

PMID- 22138063
TI  - Ulcerative colitis practice guidelines in adults.

PMID- 22138064
TI  - Squamous-cell carcinoma of the anal canal: room for improvement with targeted
      therapy.
AB  - Carcinoma of the anal canal is a rare disease accounting for 1-5% of
      gastrointestinal tract malignancies. However, its incidence is increasing
      worldwide. Chemoradiation is the standard treatment for most patients with
      squamous-cell carcinoma of the anal canal and was first described by Nigro et al.
      Since then, no other effective treatment was developed. Patients with metastatic
      disease should be considered candidates for clinical trials. New treatment
      strategies, including molecular target therapies, are warranted in order to
      improve disease control. Despite the rarity of this disease, it is urgent to
      improve its treatment by introducing targeted therapy in the arena.

PMID- 22138065
TI  - Benzyl butyl phthalate induces necrosis by AhR mediation of CYP1B1 expression in
      human granulosa cells.
AB  - We investigated the signaling pathway of the arylhydrocarbon receptor (AhR) on
      HO23 cells (immortalized human granulosa cells (hGC)) mediated by benzyl butyl
      phthalate (BBP). BBP (1 MUM) significantly increased the mRNA and protein levels
      of AhR, aryl hydrocarbon receptor nuclear translocator (ARNT) and cytochrome-P450
      (CYP)1B1 in HO23 cells. Treatment with 3',4'-dimethoxyflavone (3',4'-DMF) or AhR
      siRNA significantly reduced AhR and CYP1B1, but CYP1A1 was not affected by 3',4'
      DMF or AhR siRNA, suggesting that increases in CYP1A1 may not regulated by AhR.
      BBP induced the AhR fusion protein to localize and accumulate around the nucleus,
      and AhR heterodimerization with ARNT was observed in the nucleus by
      immunoprecipitation. Chromatin immunoprecipitation and reporter assays revealed
      the effect of BBP on CYP1B1, but not CYP1A1. Necrosis was significantly increased
      in HO23 cells after BBP treatment, and 3',4'-DMF, AhR siRNA or CYP1B1 siRNA
      knockdown blocked this phenomenon. These data suggest that BBP-induced HO23 cell
      necrosis is AhR and CYP1B1 dependent.

PMID- 22138066
TI  - A population-based study on the implementation of treatment recommendations for
      chemotherapy in early breast cancer.
AB  - BACKGROUND: There is considerable heterogeneity in the use of chemotherapy for
      patients with early breast cancer (BC), despite international recommendations
      issued from the National Comprehensive Cancer Network (NCCN), National Institutes
      of Health (NIH), and the St. Gallen biannual conference. This population-based
      study assessed the patterns of chemotherapy use in early BC. PATIENTS AND
      METHODS: The study included all or representative samples of patients with stage
      I-III BC from 7 Swiss cancer registries between 2003 and 2005. Factors modifying
      chemotherapy use were determined by logistic regression, considering patients
      receiving chemotherapy as cases (n = 1535) and the others as controls (n = 2004).
      RESULTS: Nodal involvement was by far the strongest predictor for the use of
      chemotherapy (adjusted odds ratio [OR], 9.7; 95% confidence interval [CI], 7.2
      13.0). Tumor biological characteristics such as histologic differentiation (OR,
      4.4; 95% CI, 3.2-6.2), estrogen receptor (ER) status (OR, 3.8; 95% CI, 2.6-5.5),
      human epidermal growth factor receptor 2 (HER2) status (OR, 1.9; 95% CI, 1.3
      2.7), and patient age (OR, 4.6; 95% CI, 3.5-6.2) were less important predictors
      for chemotherapy use. Socioeconomic and provider-related factors, such as patient
      education, affluence, insurance, breast surgeon's annual caseload, and case
      presentation at a multidisciplinary tumor conference did not predict the use of
      chemotherapy, with the exception of the health care provider's participation in
      clinical research (OR, 2.1; 95% CI, 1.6-2.8). The patient's region of residence
      did not predict the use of chemotherapy, but it was associated with the specific
      type of chemotherapy used. CONCLUSION: Nodal status, rather than surrogate
      markers for tumor biological features, was the predominant factor for choosing
      chemotherapy in patients with early BC in this large population study.
      Improvements should be made to increase the weight of tumor biological features
      in choosing chemotherapy in early BC.

PMID- 22138067
TI  - Antimicrobial activity of fosfomycin and tobramycin in combination against cystic
      fibrosis pathogens under aerobic and anaerobic conditions.
AB  - BACKGROUND: There is a need for new antibiotics or combination of antibiotics
      that possess activity against increasingly resistant cystic fibrosis (CF)
      respiratory pathogens such as Pseudomonas aeruginosa and MRSA. METHODS: The
      antimicrobial activity of a novel 4:1 (w/w) fosfomycin:tobramycin (F:T)
      combination against CF respiratory pathogens under both aerobic and anaerobic
      conditions was determined by MIC, time-kill and biofilm studies, and compared
      with activity of fosfomycin and tobramycin, individually. RESULTS: F:T and
      fosfomycin had excellent activity against P. aeruginosa and were more active than
      tobramycin against P. aeruginosa under anaerobic conditions with lower MIC(50),
      MIC(90) and geometric mean values. F:T (p<0.001) and fosfomycin (p<0.001) MICs
      for P. aeruginosa were significantly lower under anaerobic conditions with
      tobramycin MICs significantly higher (p<0.001). F:T and fosfomycin also had high
      activity against MRSA with both being more active than tobramycin. In time-kill
      studies, F:T was rapidly bactericidal against all 15 P. aeruginosa and 3/5 MRSA
      isolates tested. F:T also demonstrated bactericidal activity against P.
      aeruginosa grown in biofilm under both aerobic and anaerobic conditions.
      CONCLUSIONS: F:T has promising in vitro antimicrobial activity against MRSA and
      P. aeruginosa with greater activity under anaerobic conditions similar to those
      found in the CF lung.

PMID- 22138068
TI  - Microvesicles and exosomes: opportunities for cell-derived membrane vesicles in
      drug delivery.
AB  - Cell-derived membrane vesicles (CMVs) are endogenous carriers transporting
      proteins and nucleic acids between cells. They appear to play an important role
      in many disease processes, most notably inflammation and cancer, where their
      efficient functional delivery of biological cargo seems to contribute to the
      disease progress. CMVs encompass a variety of submicron vesicular structures that
      include exosomes and shedding vesicles. The lipids, proteins, mRNA and microRNA
      (miRNA) delivered by these vesicles change the phenotype of the receiving cells.
      CMVs have created excitement in the drug delivery field, because they appear to
      have multiple advantages over current artificial drug delivery systems. Two
      approaches to exploit CMVs for delivery of exogenous therapeutic cargoes in vivo
      are currently considered. One approach is based on engineering of natural CMVs in
      order to target certain cell types using CMVs loaded with therapeutic compounds.
      In the second approach, essential characteristics of CMVs are being used to
      design nano-scaled drug delivery systems. Although a number of limiting factors
      in the clinical translation of the exciting research findings so far exist, both
      approaches are promising for the development of a potentially novel generation of
      drug carriers based on CMVs.

PMID- 22138069
TI  - The development of non-viral gene-activated matrices for bone regeneration using
      polyethyleneimine (PEI) and collagen-based scaffolds.
AB  - The healing potential of scaffolds for tissue engineering can be enhanced by
      combining them with genes to produce gene-activated matrices (GAMs) for tissue
      regeneration. We examined the potential of using polyethyleneimine (PEI) as a
      vector for transfection of mesenchymal stem cells (MSCs) in monolayer culture and
      in 3D collagen-based GAMs. PEI-pDNA polyplexes were fabricated at a range of N/P
      ratios and their optimal transfection parameters (N/P 7 ratio, 2MUg dose) and
      transfection efficiencies (30+/-8%) determined in monolayer culture. The
      polyplexes were then loaded onto collagen, collagen-glycosaminoglycan and
      collagen-nanohydroxyapatite scaffolds where gene expression was observed up to 21
      days with a polyplex dose as low as 2MUg. Transient expression profiles indicated
      that the GAMs act as a polyplex depot system whereby infiltrating cells become
      transfected over time as they migrate throughout the scaffold. The collagen-nHa
      GAM exhibited the most prolonged and elevated levels of transgene expression.
      This research has thus demonstrated that PEI is a highly efficient pDNA
      transfection agent for both MSC monolayer cultures and in the 3D GAM environment.
      By combining therapeutic gene therapy with highly engineered scaffolds, it is
      proposed that these GAMs might have immense capability to promote tissue
      regeneration.

PMID- 22138070
TI  - Ocular antisense oligonucleotide delivery by cationic nanoemulsion for improved
      treatment of ocular neovascularization: an in-vivo study in rats and mice.
AB  - The efficacy of an antisense oligonucleotide (ODN17) cationic nanoemulsion
      directed at VEGF-R2 to reduce neovascularization was evaluated using rat corneal
      neovascularization and retinopathy of prematurity (ROP) mouse models. Application
      of saline solution or scrambled ODN17 solution on eyes of rats led to the highest
      extent of corneal neovascularization. The groups treated with blank nanoemulsion
      or scrambled ODN17 nanoemulsion showed moderate inhibition in corneal
      neovascularization with no significant difference with the saline and scrambled
      ODN17 control solution groups, while the groups treated with ODN17 solution or
      Avastin(r) (positive ODN17 control) clearly elicited marked significant
      inhibition in corneal neovascularization confirming the results reported in the
      literature. The highest significant corneal neovascularization inhibition
      efficiency was noted in the groups treated with ODN17 nanoemulsion (topical and
      subconjunctivally). However, in the ROP mouse model, the ODN17 in PBS induced a
      34% inhibition of retinal neovascularization when compared to the aqueous-vehicle
      injected eyes. A significantly higher inhibition of vitreal neovascularization
      (64%) was observed in the group of eyes treated with ODN17 nanoemulsion. No
      difference in extent of neovascularization was observed between blank
      nanoemulsion, scrambled ODN17 nanoemulsion, vehicle or non-treated eyes. The
      overall results indicate that cationic nanoemulsion can be considered a promising
      potential ocular delivery system and an effective therapeutic tool of high
      clinical significance in the prevention and forthcoming treatment of ocular
      neovascular diseases.

PMID- 22138071
TI  - Controlled release of a highly hydrophilic API from lipid microspheres obtained
      by prilling: analysis of drug and water diffusion processes with X-ray-based
      methods.
AB  - This study deals with the development of an oral controlled-release dosage form
      of a highly water-soluble antiepileptic drug. In this respect, drug-loaded
      spheroid particles close to 380 MUm in diameter and composed of lipid binders
      were prepared by prilling. The purpose here was to thoroughly characterize the
      controlled-release mechanism of the drug in aqueous pH-6.8 buffered dissolution
      medium. Water and drug diffusion pathways as well as related kinetic parameters
      were determined by theoretical analysis of experimental data. Conventional in
      vitro experiments performed by analytical high performance liquid chromatography
      showed that the released fraction reaches 90 wt.% only after a 24-hour immersion
      in the dissolution medium, pointing out an effective sustained release mechanism.
      Interpretation of these data was strengthened by the implementation of an
      innovative methodology involving X-ray diffraction and microtomography to follow
      the structural evolution of the drug-loaded microspheres at molecular and
      microscopic scales. This approach allowed to explicit that water and drug
      transports obey to Fickian diffusion behaviours in good agreement with Crank's
      and non-simplified Higuchi's equations, respectively. In the latter case,
      independent modelling of drug release assimilating the microspheres to a variable
      geometry reservoir was considered to refine the kinetic analysis of the diffusion
      process. The water diffusion coefficient D(w) was found equal to 6.3 * 10(-9)
      cm(2)/s and the API apparent diffusion coefficient reduced to the tortuosity of
      the matrix D(API)/tau equal to 2 * 10(-9) cm(2)/s. This study ranks among the
      rare examples of monolithic dispersion device constituted by a highly soluble
      drug incorporated inside a perfectly inert lipid matrix. The dissolution liquid
      penetrates the particles through channels progressively created by the
      solubilization of the drug itself which occurs instantaneously at the inner front
      of the liquid.

PMID- 22138072
TI  - Effective endogenous gene silencing mediated by pH responsive peptides proceeds
      via multiple pathways.
AB  - Cationic amphipathic histidine rich peptides possess high plasmid DNA and siRNA
      delivery capabilities. To further understand the pH responsive siRNA delivery
      process and evaluate the capabilities of such peptides we have investigated their
      ability to mediate specific silencing of endogenous GAPDH gene activity in MCF-7
      and A549 cells and compared this with plasmid DNA delivery. A substantial and
      selective reduction of both GAPDH activity and expression was achieved using pH
      responsive peptide vectors, which compared favourably with that mediated by
      commercially available non-viral vectors in terms of efficacy and toxicity.
      Furthermore, by comparing the efficacy of both gene delivery and silencing
      mediated by a series of such peptides, their sensitivities to known inhibitors of
      endocytotic processes, and their route of uptake via confocal live cell imaging,
      we show that both plasmid DNA and siRNA are internalised via endocytosis. However
      siRNA entry facilitated by LAH4-L1, proceeds via a cholesterol dependent
      mechanism, in contrast to DNA transfer which is associated with clathrin
      dependent endocytosis. Furthermore, using peptides that respond at increasingly
      acidic pH, we demonstrate that the route of entry for the siRNA that ultimately
      mediates silencing is peptide specific and whilst some pH responsive peptides
      promote the escape of labelled siRNA from endosomes, others may promote entry via
      alternative mechanisms.

PMID- 22138073
TI  - Novel cholesterol spermine conjugates provide efficient cellular delivery of
      plasmid DNA and small interfering RNA.
AB  - New polycationic lipids corresponding to the two different classes of amphiphiles
      ("head-tail" and "gemini") were designed and used as components of non-viral gene
      delivery systems. The hydrophobic domain of lipids is based on the cholesterol
      residue and the hydrophilic one--on the naturally occurring polyamine--spermine.
      Ester and carbamate linker groups as well as oligomethylene spacers of various
      lengths were used to connect cholesterol and spermine motifs in order to estimate
      the structure-activity relationships of novel polycationic lipids and to
      determine an effective and safe transfectant suitable for the delivery of
      different nucleic acids. The cationic liposomes composed of the synthesized
      polycationic lipids and DOPE provided delivery of FITC-labeled oligonucleotide,
      plasmid DNA and siRNA into HEK293 cells with an efficiency significantly higher
      than that of Lipofectamine 2000. We found that the transfection activity of
      polycationic lipids is influenced by a linker type, a spacer length and the
      amount of cholesterol residues. The lipid containing two cholesterol units,
      carbamate linker and spacer of six methylene groups demonstrated the best in
      vitro transfection results among other analogues tested and was defined as a
      promising candidate for further transfection studies to be hold in vivo.

PMID- 22138074
TI  - Prodrug approaches to reduce hyperexcitation in the CNS.
AB  - Hyperexcitation in the central nervous system is the root cause of a number of
      disorders of the brain ranging from acute injury to chronic and progressive
      diseases. The major limitation to treatment of these ailments is the miniscule,
      yet formidable blood-brain barrier. To deliver therapeutic agents to the site of
      desired action, a number of biomedical engineering strategies have been developed
      including prodrug formulations that allow for either passive diffusion or active
      transport across this barrier. In the case of prodrugs, once in the brain
      compartment, the active therapeutic agent is released. In this review, we discuss
      in some detail a number of factors related to treatment of central nervous system
      hyperexcitation including molecular targets, disorders, prodrug strategies, and
      focused case studies of a number of therapeutics that are at a variety of stages
      of clinical development.

PMID- 22138075
TI  - The bariatric surgery patient: lost to follow-up; from morbid obesity to severe
      malnutrition.
AB  - OBJECTIVE: To describe the potential long-term risk of malnutrition after Roux-en
      Y gastric bypass (GBP) through an uncommon occurrence of inflammatory bowel
      disease (IBD) postoperatively, which posed a serious threat to the nutritional
      status and the life of the patient. METHODS: We present a case report of a 44
      year-old woman in whom Crohn disease developed 4 years after she had undergone
      GBP. The double insult of IBD and GBP resulted in severe malnutrition, with a
      serum albumin concentration of 0.9 g/dL (reference range, 3.5 to 5.0), weight
      loss, and watery diarrhea necessitating 6 hospital admissions during a period of
      7 months. RESULTS: Ultimately, the administration of total parenteral nutrition
      with aggressive macronutrient, vitamin, and mineral repletion resulted in
      substantial improvement in the patient's strength, function, and quality of life,
      in parallel with diminished symptoms of IBD. CONCLUSION: Rarely, IBD develops
      after GBP, but the relationship between the 2 conditions remains unclear.
      Regardless, in addition to the altered anatomy after bariatric surgery, the
      further insult of IBD poses a severe threat to the nutritional status of affected
      patients. Malnutrition needs to be recognized and aggressively treated.
      Nutritional markers should be followed closely in this population of bariatric
      patients in an effort to avert the onset of severe malnutrition.

PMID- 22138076
TI  - Subacute thyroiditis manifesting as a thyroid mass, vocal cord paralysis, and
      hypercalcemia.
AB  - OBJECTIVE: To report a case of subacute thyroiditis manifesting as a thyroid
      mass, vocal cord paralysis, and hypercalcemia. METHODS: We describe the clinical,
      laboratory, and radiologic findings in a patient with an unusual clinical course
      of subacute thyroiditis. RESULTS: A 65-year-old woman presented with a hoarse
      voice and an enlarging tender mass in the right side of the neck. On admission,
      thyroid function was consistent with thyrotoxicosis from subacute thyroiditis.
      Laboratory studies showed a corrected serum calcium concentration of 11.4 mg/dL,
      intact parathyroid hormone of 125 pg/mL, 25-hydroxyvitamin D of 12 ng/mL, and
      creatinine of 1.8 mg/dL. Computed tomography of the neck without use of a
      contrast agent showed a heterogeneous mass in the right side of the neck in
      conjunction with deviation of the trachea from right to left but without invasion
      of the trachea. Thyroid ultrasonography disclosed a heterogeneous mass in the
      right thyroid lobe measuring 4.7 cm by 5.5 cm by 4.5 cm. Flexible laryngoscopy
      revealed right vocal cord paralysis. Treatment with a course of prednisone
      yielded normalization of the serum calcium level, improvement in her voice, and a
      decrease in size of the thyroid mass. Four months after initial presentation of
      the patient, thyroid hormone levels became normal, she was clinically euthyroid,
      and she had a full recovery of her voice. Her serum calcium concentration was
      normal (9.8 mg/dL) in association with a near-normal parathyroid hormone level of
      90 pg/mL. The 25-hydroxyvitamin D and creatinine values were also normal.
      Repeated thyroid ultrasonography showed a smaller right thyroid lobe with a
      dominant nodule measuring 2.0 cm by 1.3 cm by 1.4 cm in the right upper pole.
      CONCLUSION: This case illustrates that subacute thyroiditis can have the unusual
      initial manifestations of a thyroid mass, vocal cord paralysis, and
      hypercalcemia. In similar patients, a trial of corticosteroid therapy may be
      warranted in an effort to improve clinical symptoms and thus avoid unnecessary
      surgical treatment.

PMID- 22138077
TI  - Ethnic disparity in hemoglobin A1c levels among normoglycemic offspring of
      parents with type 2 diabetes mellitus.
AB  - OBJECTIVE: To investigate the racial/ethnic disparities in hemoglobin A1c levels
      among nondiabetic persons with similar parental history of type 2 diabetes
      mellitus. METHODS: We studied a community-based sample of adult offspring of
      parents with type 2 diabetes mellitus. Measurements included anthropometry,
      hematology assessments, serial fasting plasma glucose, oral glucose tolerance
      testing, plasma insulin, hemoglobin A1c, insulin sensitivity, and beta-cell
      function, using a homeostasis model assessment. RESULTS: The study included 302
      participants (135 white, 167 black). Compared with white participants, black
      participants had lower fasting plasma glucose levels (91.9 +/- 0.51 mg/dL vs 93.6
      +/- 0.50 mg/dL, P = .015), lower area under the curve of plasma glucose during
      oral glucose tolerance testing (P = <.001), higher body mass index (31.1 +/- 0.61
      kg/m2 vs 28.5 +/- 0.57 kg/m2, P = <.001), and similar insulin sensitivity and
      beta-cell function. Hemoglobin A1c was higher in black participants than in white
      participants (5.68 +/- 0.033% vs 5.45 +/- 0.028%, P<.001). The absolute black
      white difference in hemoglobin A1c level of approximately 0.22% persisted after
      adjusting for age, hemoglobin, hematocrit, body mass index, waist circumference,
      fasting plasma glucose, glucose area under the curve, and other covariates.
      CONCLUSIONS: Among healthy offspring of parents with type 2 diabetes mellitus in
      this study, African American participants had higher hemoglobin A1c levels than
      white participants after adjusting for age, adiposity, blood glucose, and known
      variables. Thus, plasma glucose level is more valid than hemoglobin A1c for
      diagnosing prediabetes or diabetes in black persons.

PMID- 22138078
TI  - Adapting to the new consensus guidelines for managing hyperglycemia during
      critical illness: the updated Yale insulin infusion protocol.
AB  - OBJECTIVE: To report our preliminary experience with the revised, more
      conservative Yale insulin infusion protocol (IIP) that targets blood glucose
      concentrations of 120 to 160 mg/dL. METHODS: We prospectively tracked clinical
      responses to the new IIP in our medical intensive care unit (ICU) by recording
      data on the first 115 consecutive insulin infusions that were initiated. All
      blood glucose values; insulin doses; nutritional support including intravenous
      dextrose infusions; caloric values for enteral and parenteral nutrition; and use
      of vasopressors, corticosteroids, and hemodialysis or continuous venovenous
      hemodialysis were collected from the hospital record. RESULTS: The IIP was used
      115 times in 90 patients (mean age, 62 [+/-14 years]; 51% male; 35% ethnic
      minorities; 66.1% with history of diabetes). The mean admission Acute Physiology
      and Chronic Health Evaluation II score was 24.4 (+/-7.5). The median duration of
      insulin infusion was 59 hours. The mean baseline blood glucose concentration was
      306.1 (+/-89.8) mg/dL, with the blood glucose target achieved after a median of 7
      hours. Once the target was reached, the mean IIP blood glucose concentration was
      155.9 (+/-22.9) mg/dL (median, 150 mg/dL). The median insulin infusion rate
      required to reach and maintain the target range was 3.5 units/h. Hypoglycemia was
      rare, with 0.3% of blood glucose values recorded being less than 70 mg/dL and
      only 0.02% being less than 40 mg/dL. In all cases, hypoglycemia was rapidly
      corrected using intravenous dextrose with no evident untoward outcomes.
      CONCLUSIONS: The updated Yale IIP provides effective and safe targeted blood
      glucose control in critically ill patients, in compliance with recent national
      guidelines. It can be easily implemented by hospitals now using the original Yale
      IIP.

PMID- 22138079
TI  - Association of ipilimumab therapy for advanced melanoma with secondary adrenal
      insufficiency: a case series.
AB  - OBJECTIVE: To present a case series of ipilimumab-related secondary adrenal
      insufficiency. METHODS: In this cases series, we review the presentation,
      evaluation, diagnosis, and management of patients with advanced melanoma who
      received ipilimumab and were referred to our endocrinology clinic for evaluation
      of hormonal abnormalities. RESULTS: Seven patients presented with symptoms,
      signs, or biochemical evidence of adrenal insufficiency 6 to 12 weeks after
      starting ipilimumab therapy. Ipilimumab is a cytotoxic T-lymphocyte antigen 4
      (CTLA-4) monoclonal antibody that is approved for the treatment of metastatic
      melanoma and has widespread use for this disease. All 7 patients had biochemical
      evidence of profound secondary adrenal insufficiency. Thyroid function
      abnormalities, central hypogonadism, and low insulinlike growth factor 1 levels
      were seen in a subset of patients. Only 2 patients had abnormal findings on
      pituitary magnetic resonance imaging. Posterior pituitary function remained
      normal. CONCLUSIONS: Our findings suggest that the enhanced immune response
      associated with ipilimumab therapy may have a predilection for corticotroph and
      possibly thyrotroph cells. We recommend periodic hypothalamic-pituitary-adrenal
      axis monitoring for patients on this therapy.

PMID- 22138080
TI  - Repairing a "broken heart" with hormone replacement therapy: case report of
      cardiogenic shock due to undiagnosed pituitary insufficiency.
AB  - OBJECTIVES: To indicate cardiogenic shock as a very rare but serious clinical
      consequence of untreated panhypopituitarism attributable to Sheehan syndrome; to
      emphasize the importance of eliciting a detailed endocrine and obstetric history
      in women presenting with idiopathic heart failure; to highlight the diagnostic
      shortcomings of screening for thyroid dysfunction solely with thyroid-stimulating
      hormone determinations; and to report the reversibility of severe heart failure
      induced by long-term pituitary insufficiency. METHODS: Described is a case report
      of a 35-year-old woman who presented with severe congestive heart failure,
      hypotension, and confusion. Her 2-dimensional echocardiogram revealed appreciable
      systolic and diastolic dysfunction. In screening for possible endocrine causes of
      heart failure, a normal thyroid-stimulating hormone level of 0.72 mIU/L
      (reference range, 0.35 to 5.5) was unremarkable; however, a profoundly low free
      thyroxine level of 0.12 ng/dL (reference range, 0.9 to 1.8) led clinicians to
      pursue a work-up of central hypothyroidism. RESULTS: Endocrine testing confirmed
      the presence of panhypopituitarism and adrenal insufficiency. Magnetic resonance
      imaging of the brain revealed empty sella syndrome. Further questioning of the
      patient revealed a history of extensive postpartum bleeding 15 years earlier,
      failure to lactate, and secondary amenorrhea--all consistent with undiagnosed
      Sheehan syndrome. In the hospital, the patient was treated with intravenously
      administered corticosteroids and levothyroxine. Her mental status and symptomatic
      heart failure improved dramatically. After 9 months of oral levothyroxine and
      glucocorticoid therapy, the patient remained asymptomatic, and repeated
      echocardiography indicated completely normalized cardiac function. CONCLUSION:
      Severe heart failure and cardiogenic shock can be a very rare (but fortunately
      reversible) complication of long-standing panhypopituitarism resulting from
      undiagnosed Sheehan syndrome.

PMID- 22138081
TI  - Use of recombinant human hyaluronidase to accelerate rapid insulin analogue
      absorption: experience with subcutaneous injection and continuous infusion.
AB  - OBJECTIVE: To discuss clinical studies in which recombinant human hyaluronidase
      (rHuPH20) was used to increase insulin dispersion and accelerate its absorption.
      METHODS: We reviewed 10 pertinent clinical studies, 8 of which had data
      available. RESULTS: In 4 euglycemic clamp studies, coinjection of rHuPH20
      consistently yielded acceleration of insulin absorption, providing twice the
      insulin exposure during the first hour, greater and earlier peak exposure, and
      half the exposure beyond 2 hours after injection. Insulin-action profiles were
      similarly accelerated, with a 15-minute faster onset of insulin action and a 45
      minute shorter duration of action for each of the 3 commercial rapid-acting
      insulin analogues. Infusion aspart insulin formulated with rHuPH20 also
      accelerated insulin absorption and action over the infusion set life when
      delivered by insulin pump. Administration of rHuPH20 reduced the inconsistency of
      insulin absorption and action profiles attributable to 3 factors-lack of
      reproducibility after identical injections, differences across insulin dose
      ranges, and changes over infusion site life. The rHuPH20-facilitated ultrafast
      profile consistently reduced hyperglycemic excursions both in injections
      immediately preceding liquid test meals and in bolus infusions immediately before
      solid test meals. rHuPH20-facilitated insulin administration has been well
      tolerated, with safety and tolerability similar to those with the comparator
      insulin alone. CONCLUSION: rHuPH20 accelerates insulin-action profiles to an
      extent comparable to the difference between rapid-acting insulin analogue
      profiles and those of regular insulin. Studies are currently under way to
      characterize the effect on diabetes management end points (including hemoglobin
      A1c, blood glucose, and rates of hyperglycemia) of insulin analogues coformulated
      with rHuPH20 for treatment of both type 1 and type 2 diabetes.

PMID- 22138083
TI  - PHACES syndrome.

PMID- 22138084
TI  - Immunogenicity of Lactobacillus-expressing VP2 and VP3 of the infectious
      pancreatic necrosis virus (IPNV) in rainbow trout.
AB  - Infectious pancreatic necrosis virus (IPNV) infects salmonid fish with high
      mortality and causes serious economic losses to salmonid aquaculture.
      Lactobacillus strains have a number of properties that make them attractive
      candidates as delivery vehicles for the presentation to the mucosa of compounds
      with pharmaceutical interest, in particular vaccines. Here,
      Lactobacilli/Escherichia coli shuttle vector pPG1 (surface-displayed) or pPG2
      (secretory) with the capsid VP2 gene inserted was transformed into Lactobacillus
      casei to yield two recombinant strains: Lc:PG1-VP2 and Lc:PG2-VP2, respectively.
      Rainbow trout immunized respectively with Lc:PG1-VP2, Lc:PG2-VP2, Lc:PG1-VP3 and
      Lc:PG2-VP3 elicited anti-IPNV immune responses (serum IgM) via oral route.
      Statistical results of serum IgM titer with neutralizing activity showed that
      immunogenicity of Lc:PG2-VP2 was more powerful than that of Lc:PG1-VP2 (P <
      0.001), Lc:PG1-VP3 (P < 0.001) and Lc:PG2-VP3 (P < 0.001), which was confirmed by
      viral loads reduction analyzed by real-time RT-PCR in orally immunized rainbow
      trout after virus challenge. Comparing with negative control, rainbow trout
      orally dosed with Lc:PG2-VP2 resulted in ~46-fold reduction in virus load on days
      10 post viral challenge as well as Lc:PG1-VP2(~20-fold), Lc:PG2-VP3(~6-fold) and
      Lc:PG1-VP3(~3-fold). Taken together, Lc:PG2-VP2 exhibited a more appropriate
      candidate as live bacteria vaccine against IPNV infection in rainbow trout.

PMID- 22138085
TI  - The effect of colonoscopy preparation quality on adenoma detection rates.
AB  - BACKGROUND: Colonoscopy reduces the risk of colorectal cancer mortality by
      removing precancerous adenomas. The detection rate of subcentimeter (<10 mm)
      polyps is lower for procedures with inadequate preparation quality. OBJECTIVE: To
      compare the adenoma detection rates of small (6-9 mm) and diminutive (<= 5 mm)
      adenomas in patients with poor and fair quality preparations with those with
      adequate quality preparations. DESIGN: Cross-sectional study and multivariable,
      hierarchical model. SETTING: Roudebush Veterans Affairs Medical Center. PATIENTS:
      This study involved 8800 colonoscopies performed from 2001 to 2010. MAIN OUTCOME
      MEASUREMENTS: Preparation quality rating, polyp size, and polyp histology.
      RESULTS: Preparation quality was rated as fair in 2809 (31.9%) and poor in 829
      (9.4%) colonoscopies. In patients with poor compared with adequate quality, the
      detection rate was lower for diminutive adenomas (odds ratio [OR] 0.57; 95% CI,
      0.47-0.70) but not for small adenomas (OR 0.84; 95% CI, 0.65-1.07). There were no
      differences in the detection rate of diminutive (OR 1.08; 95% CI, 0.94-1.24]) or
      small (OR 1.09; 95% CI, 0.94-1.27) adenomas in patients with fair compared with
      adequate quality preparation. Detection of advanced histology in patients with
      poor preparation quality was lower than in those with adequate quality (P = .027;
      3.3% vs 5.0%), but there was no difference in those with fair compared with
      adequate quality (P = .893; 4.9% vs 5.0%). LIMITATIONS: Single-center study; no
      standardization of preparation quality or size measurements. CONCLUSIONS: A fair
      preparation quality rating does not decrease the detection rate for adenomas of
      any size or for advanced histology, suggesting that fair quality may be
      considered adequate and that follow-up intervals may not need to be shortened.
      Poor preparation quality decreases the detection rate of diminutive adenomas and
      advanced histology, suggesting substandard colonoscopy performance.

PMID- 22138087
TI  - The role of ADAM-mediated shedding in vascular biology.
AB  - Within the vasculature the disintegrins and metalloproteinases (ADAMs) 8, 9, 10,
      12, 15, 17, 19, 28 and 33 are expressed on endothelial cells, smooth muscle cells
      and on leukocytes. As surface-expressed proteases they mediate cleavage of
      vascular surface molecules at an extracellular site close to the membrane. This
      process is termed shedding and leads to the release of a soluble substrate
      ectodomain thereby critically modulating the biological function of the
      substrate. In the vasculature several surface molecules undergo ADAM-mediated
      shedding including tumour necrosis factor (TNF) alpha, interleukin (IL) 6
      receptor alpha, L-selectin, vascular endothelial (VE)-cadherin, the transmembrane
      CX3C-chemokine ligand (CX3CL) 1, Notch, transforming growth factor (TGF) and
      heparin-binding epidermal growth factor (HB-EGF). These substrates play distinct
      roles in vascular biology by promoting inflammation, permeability changes,
      leukocyte recruitment, resolution of inflammation, regeneration and/or
      neovascularisation. Especially ADAM17 and ADAM10 are capable of cleaving many
      substrates with diverse function within the vasculature, whereas other ADAMs have
      a more restricted substrate range. Therefore, targeting ADAM17 or ADAM10 by
      pharmacologic inhibition or gene knockout not only attenuates the inflammatory
      response in animal models but also affects tissue regeneration and
      neovascularisation. Recent discoveries indicate that other ADAMs (e.g. ADAM8 and
      9) also play important roles in vascular biology but appear to have more
      selective effects on vascular responses (e.g. on neovascularisation only).
      Although, targeting of ADAM17 and ADAM10 in inflammatory diseases is still a
      promising approach, temporal and spatial as well as substrate-specific inhibition
      approaches are required to minimise undesired side effects on vascular cells.

PMID- 22138086
TI  - Interleukin-6 signalling: more than Jaks and STATs.
AB  - The hallmark of signalling by many cytokines is the activation of the Janus
      kinase (Jak)/signal transducer and activator of transcription (STAT) pathway.
      However, cytokines additionally activate other pathways. In past years we
      realised that these pathways significantly contribute to the physiological
      functions of IL-6 and pathophysiological functions in the context of many
      inflammatory and proliferative diseases. Whereas other articles in this issue of
      the European Journal of Cell Biology focus on STAT activation and its regulation
      we here aim to summarise our knowledge and some remaining questions on
      interleukin-6 (IL-6)-induced STAT-independent pathways as well as the cross-talk
      with the Jak/STAT pathway. In the early stages of studying cytokine signalling we
      were used to analysing individual signalling pathways. These days we know about
      the importance of both, the crosstalk between pathways initiated by combinations
      of cytokines as well as the crosstalk between individual pathways initiated by a
      single cytokine. Whereas the inter-cytokine crosstalk can be studied relatively
      easily, more sophisticated experimental approaches are required to elucidate the
      intra-cytokine crosstalk.

PMID- 22138088
TI  - Expression of spinal cord microRNAs in a rat model of chronic neuropathic pain.
AB  - Neuropathic pain is accompanied by significant alterations of gene expression
      patterns in the somatosensory nervous system. The spinal cord is particularly
      prone to neuroplastic changes. Since the expression of microRNAs (miRNAs) has
      been linked to numerous pathophysiological processes, a contribution of miRNAs to
      the maladaptive plasticity of the spinal cord in neuropathic pain is possible.
      Aim of the present study therefore was to characterize the specific expression
      pattern of miRNAs in the rat spinal cord. Furthermore, we evaluated the time
      dependent changes in expression patterns of spinal miRNAs in the chronic
      constriction injury (CCI) model of neuropathic pain in rats. Results from miRNA
      microarrays revealed a distinct expression pattern of miRNAs in the rat spinal
      cord. MiRNAs-494, -720, -690 and -668 showed the highest signal intensities.
      Members of the let-7 family as well as miR-124 belong to the group of the most
      highly expressed miRNAs. Induction of neuropathic pain by CCI did not lead to
      relevant differences in spinal miRNA expression levels compared to sham-operated
      animals at any studied time point. Therefore, modulation of miRNAs does not seem
      to contribute significantly to the changes in gene expression that cause neural
      plasticity in the spinal cord in this model of chronic neuropathic pain.

PMID- 22138089
TI  - Orexins promote survival of rat cortical neurons.
AB  - Orexin A and B (hypocretin-1 and -2) are hypothalamic peptides that exert their
      biological functions by stimulation of two specific, membrane-bound receptors,
      OX(1)R and OX(2)R. Recently, we have demonstrated the expression of both types of
      orexin receptors in rat cortical neurons, with the OX(2)R level being markedly
      higher compared to OX(1)R. In the present study we investigated the receptor
      mediated effects of orexin A, an agonist of OX(1)R and OX(2) R, orexin B and
      [Ala(11)-D-Leu(15)]orexin B, preferential agonists of OX(2)R, on survival of
      cultured neurons derived from rat cerebral cortex. The three tested peptides
      markedly increased neuronal viability in a concentration-dependent manner. The
      pro-survival properties of orexins were associated with an attenuation of caspase
      3 activity. Comparable potency of orexin A, orexin B and [Ala(11)-D
      Leu(15)]orexin B suggests a predominant role of OX(2)R in the studied phenomenon.
      Our findings provide new insights into the role of orexins in CNS as potential
      neuroprotective factors.

PMID- 22138090
TI  - Tooth movements are guided by specific contact areas between the tooth root and
      the jaw bone: A dynamic 3D microCT study of the rat molar.
AB  - Teeth sustain high loads over a lifetime and yet intact tooth failure is rare.
      The different structures of the tooth, jaw bone and the intervening soft
      periodontal ligament enable the tooth to endure repeated loading during
      mastication. Although mechanical and functional properties of the different
      components are thoroughly investigated, the manner in which the whole tooth
      functions under load is still enigmatic. A custom-made loading system inside a
      microCT scanner was used to directly visualize the root movements in relation to
      the jaw bone as the rat molar tooth was loaded. At low loads no contact was
      observed between the root surface and the bone, whereas at higher loads three
      specific contact areas between the root surface and the jaw bone were observed.
      These contact areas restrict tooth movement in the buccal-lingual direction, but
      enable the tooth to rock in a "seesaw" like manner in the distal-mesial
      direction. The contact areas appear to play a role in determining tooth motion
      and in turn define the manner in which the whole tooth moves when loaded. These
      observations are important for understanding basic structure-function relations
      of the tooth-PDL-bone system, and have direct implications for better
      understanding pathological and therapeutic processes in orthodontics,
      periodontics and jaw bone regeneration.

PMID- 22138091
TI  - Analysis of the yeast nucleoporin Nup188 reveals a conserved S-like structure
      with similarity to karyopherins.
AB  - Nuclear pore complexes (NPCs) embedded in the double nuclear membrane mediate the
      entire nucleocytoplasmic transport between the nucleus and cytoplasm. Each NPC is
      composed of about 30 different proteins (nucleoporins or Nups), which exist in
      multiple (8, 16 or 32) copies within the NPC scaffold. Recently, we have
      identified and characterized the large structural Nups, Nup188 and Nup192, from
      the thermophilic eukaryote Chaetomium thermophilum, which exhibited superior
      properties for biochemical and structural studies, when compared to their
      mesophilic orthologs. Here, we study the large structural Nups from the model
      organism yeast Saccharomyces cerevisiae. Our data show that yeast Nup188 like its
      thermophilic orthologue ctNup188 exhibits a twisted S-like structure, which
      flexibly binds the linker nucleoporin Nic96 via a short conserved alpha-helix
      motif. Using bioinformatic methods, we have generated a pseudo-atomic structural
      model of Nup188 and its related Nup192, which further strengthens the view that
      the large alpha-solenoid structural Nups are related to karyopherins.

PMID- 22138092
TI  - A mathematical model for the dynamics of cancer hepatocytes under therapeutic
      actions.
AB  - This paper deals with the development of a mathematical model for the in vitro
      dynamics of malignant hepatocytes exposed to anti-cancer therapies. The model
      consists of a set of integro-differential equations describing the dynamics of
      tumor cells under the effects of mutation and competition phenomena, interactions
      with cytokines regulating cell proliferation as well as the action of cytotoxic
      drugs and targeted therapeutic agents. Asymptotic analysis and simulations,
      developed with an exploratory aim, are addressed to enlighten the role played by
      the biological phenomena under consideration in the dynamics of hepatocellular
      carcinoma, with particular reference to the intra-tumor heterogeneity and the
      response to therapies. The obtained results suggest that cancer progression
      selects for highly proliferative clones. Moreover, it seems that intra-tumor
      heterogeneity makes targeted therapeutic agents to be less effective than
      cytotoxic drugs and a joint action of these two classes of agents may mutually
      increase their efficacy. Finally, it is highlighted how targeted therapeutic
      agents might act as an additional selective pressure leading to the selection for
      the most fitting, and then most resistant, cancer clones.

PMID- 22138093
TI  - Relating ranging ecology, limb length, and locomotor economy in terrestrial
      animals.
AB  - Ecomorphological analyses have identified a number of important evolutionary
      trends in vertebrate limb design, but the relationships between daily travel
      distance, locomotor ecology, and limb length in terrestrial animals remain poorly
      understood. In this paper I model the net rate of energy intake as a function of
      foraging efficiency, and thus of locomotor economy; improved economy leads to
      greater net energy intake. However, the relationship between locomotor economy
      and net intake is highly dependent on foraging efficiency; only species with low
      foraging efficiencies experience strong selection pressure for improved locomotor
      economy and increased limb length. Examining 237 terrestrial species, I find that
      nearly all taxa obtain sufficiently high foraging efficiencies that selection for
      further increases in economy is weak. Thus selection pressures for increased
      economy and limb length among living terrestrial animals may be relatively weak
      and similar in magnitude across ecologically diverse species. The Economy
      Selection Pressure model for locomotor economy may be useful in investigating the
      evolution of limb design in early terrestrial taxa and the coevolution of
      foraging ecology and locomotor anatomy in lineages with low foraging
      efficiencies.

PMID- 22138094
TI  - Alignment free comparison: similarity distribution between the DNA primary
      sequences based on the shortest absent word.
AB  - This work proposes an alignment free comparison model for the DNA primary
      sequences. In this paper, we treat the double strands of the DNA rather than
      single strand. We define the shortest absent word of the double strands between
      the DNA sequences and some properties are studied to speed up the algorithm for
      searching the shortest absent word. We present a novel model for comparison, in
      which the similarity distribution is introduced to describe the similarity
      between the sequences. A distance measure is deduced based on the Shannon entropy
      meanwhile is used in phylogenetic analysis. Some experiments show that our model
      performs well in the field of sequence analysis.

PMID- 22138095
TI  - Antibodies to CV2/CRMP5 in neuromyelitis optica-like disease: case report and
      review of the literature.
AB  - Neuromyelitis optica (NMO) is associated with antibodies to aquaporin-4 (termed
      NMO-IgG or AQP4-Ab) in 60-90% of cases. Little is known about the aetiology of
      NMO in NMO-IgG/AQP4-Ab negative patients. Here we report on CV2/CRMP5 antibodies
      in a 69-year-old male patient with NMO-IgG/AQP4-Ab negative NMO. The association
      of CV2/CRMP5-Ab with prostate cancer suggests a paraneoplastic aetiology of NMO
      in our patient. Our report strengthens the case of antibodies other than AQP4-Ab
      being involved in the immunopathogenesis in a subset of patients with NMO. We
      conclude that CV2/CRMP5-Ab should be included in the differential diagnosis of
      NMO, in particular if AQP4-Ab are negative and irrespective of whether a tumour
      is known or not. We recommend that recombinant tests, which are increasingly used
      because of their higher sensitivity and specificity, should always be accompanied
      by standard indirect immunofluorescence employing brain tissue sections in order
      to avoid CV2/CRMP5-Ab or other paraneoplastic antibodies being overlooked. In
      addition, we provide a comprehensive review of all patients with CV2/CRMP5-Ab and
      NMO-like disease published in the English literature so far.

PMID- 22138096
TI  - Predictability of adjuvant trastuzumab benefit in N9831 patients using the
      ASCO/CAP HER2-positivity criteria.
AB  - The 2007 American Society of Clinical Oncology and College of American
      Pathologists (ASCO/CAP) joint guidelines defined criteria for HER2 positivity of
      tumors that modified those of the US Food and Drug Administration (FDA), causing
      some confusion and uncertainty among clinicians. Using data from the HER2
      positive breast cancer adjuvant trial N9831, we compared eligibility for patients
      who met both criteria, and disease-free survival (DFS) was assessed by Cox
      proportional hazards regression. The number of patients in the N9831 trial
      retrospectively eligible for trastuzumab therapy was decreased when ASCO/CAP
      criteria vs FDA criteria were applied to immunohistochemistry and/or fluorescence
      in situ hybridization results (107 [3.7%] of 2904 patients with
      immunohistochemistry results, 37 [1.3%] of 2809 patients with fluorescence in
      situ hybridization results, and 47 [1.7%] of 2809 patients with both results).
      Improvement in DFS was similar among patients treated with trastuzumab under
      either set of criteria (concurrent trastuzumab and chemotherapy compared with
      chemotherapy alone: by ASCO/CAP criteria, hazard ratio of DFS = 0.59, 95%
      confidence interval = 0.48 to 0.73; by FDA criteria but not ASCO/CAP criteria,
      hazard ratio = 0.60, 95% confidence interval = 0.12 to 3.13; number needed to
      treat to prevent one additional DFS event at 5 years: 10 and 11.2 patients,
      respectively). Following the 2007 ASCO/CAP criteria for HER2 positivity would
      negate the option of potentially life-saving trastuzumab therapy for a small but
      meaningful group of patients. We recommend using FDA-approved HER2 criteria for
      therapeutic decision making.

PMID- 22138098
TI  - [Solution to case 44. Autoimmune pancreatitis with renal involvement before and
      after the administration of corticosteroids].

PMID- 22138097
TI  - Economic evaluation of genomic test-directed chemotherapy for early-stage lymph
      node-positive breast cancer.
AB  - BACKGROUND: Multi-parameter genomic tests identify patients with early-stage
      breast cancer who are likely to derive little benefit from adjuvant chemotherapy.
      These tests can potentially spare patients the morbidity from unnecessary
      chemotherapy and reduce costs. However, the costs of the test must be balanced
      against the health benefits and cost savings produced. This economic evaluation
      compared genomic test-directed chemotherapy using the Oncotype DX 21-gene assay
      with chemotherapy for all eligible patients with lymph node-positive, estrogen
      receptor-positive early-stage breast cancer. METHODS: We performed a cost-utility
      analysis using a state transition model to calculate expected costs and benefits
      over the lifetime of a cohort of women with estrogen receptor-positive lymph node
      positive breast cancer from a UK perspective. Recurrence rates for Oncotype DX
      selected risk groups were derived from parametric survival models fitted to data
      from the Southwest Oncology Group 8814 trial. The primary outcome was the
      incremental cost-effectiveness ratio, expressed as the cost (in 2011 GBP) per
      quality-adjusted life-year (QALY). Confidence in the incremental cost
      effectiveness ratio was expressed as a probability of cost-effectiveness and was
      calculated using Monte Carlo simulation. Model parameters were varied
      deterministically and probabilistically in sensitivity analysis. Value of
      information analysis was used to rank priorities for further research. RESULTS:
      The incremental cost-effectiveness ratio for Oncotype DX-directed chemotherapy
      using a recurrence score cutoff of 18 was L5529 (US $8852) per QALY. The
      probability that test-directed chemotherapy is cost-effective was 0.61 at a
      willingness-to-pay threshold of L30 000 per QALY. Results were sensitive to the
      recurrence rate, long-term anthracycline-related cardiac toxicity, quality of
      life, test cost, and the time horizon. The highest priority for further research
      identified by value of information analysis is the recurrence rate in test
      selected subgroups. CONCLUSIONS: There is substantial uncertainty regarding the
      cost-effectiveness of Oncotype DX-directed chemotherapy. It is particularly
      important that future research studies to inform cost-effectiveness-based
      decisions collect long-term outcome data.

PMID- 22138099
TI  - Multiple exocytotic markers accumulate at the sites of perifungal membrane
      biogenesis in arbuscular mycorrhizas.
AB  - Arbuscular mycorrhizas (AMs) are symbiotic interactions established within the
      roots of most plants by soil fungi belonging to the Glomeromycota. The extensive
      accommodation of the fungus in the root tissues largely takes place
      intracellularly, within a specialized interface compartment surrounded by the so
      called perifungal membrane, an extension of the host plasmalemma. By combining
      live confocal imaging of green fluorescent protein (GFP)-tagged proteins and
      transmission electron microscopy (TEM), we have investigated the mechanisms
      leading to the biogenesis of this membrane. Our results show that pre-penetration
      responses and symbiotic interface construction are associated with extensive
      membrane dynamics. They involve the main components of the exocytotic machinery,
      with a major participation of the Golgi apparatus, as revealed by both TEM and in
      vivo GFP imaging. The labeling of known exocytosis markers, such as v-SNARE
      proteins of the VAMP72 family and the EXO84b subunit of the exocyst complex,
      allowed live imaging of the cell components involved in perifungal membrane
      construction, clarifying how this takes place ahead of the growing intracellular
      hypha. Lastly, our novel data are used to illustrate a model of membrane dynamics
      within the pre-penetration apparatus during AM fungal penetration.

PMID- 22138100
TI  - 5'-monohydroxyphylloquinone is the dominant naphthoquinone of PSI in the green
      alga Chlamydomonas reinhardtii.
AB  - Thylakoid membranes contain two types of quinones, benzoquinone (plastoquinone)
      and naphthoquinone, which are involved in photosynthetic electron transfer.
      Unlike the benzoquinone, the chemical species of naphthoquinone present
      (phylloquinone, menaquinone-4 and 5'-monohydroxyphylloquinone) varies depending
      on the oxygenic photosynthetic organisms. The green alga Chlamydomonas
      reinhardtii has been used as a model organism to study the function of the
      naphthoquinone bound to PSI. However, the level of phylloquinone and the presence
      of other naphthoquinones in this organism remain unknown. In the present study,
      we found that 5'-monohydroxyphylloquinone is the predominant naphthoquinone in
      cell and thylakoid extracts based on the retention time during reverse phase
      HPLC, absorption and mass spectrometry measurements. It was shown that 5'
      monohydroxyphylloquinone is enriched 2.5-fold in the PSI complex as compared with
      thylakoid membranes but that it is absent from PSI-deficient mutant cells. We
      also found a small amount of phylloquinone in the cells and in the PSI complex
      and estimated that accumulated 5'-monohydroxyphylloquinone and phylloquinone
      account for approximately 90 and 10%, respectively, of the total naphthoquinone
      content. The ratio of these two naphthoquinones remained nearly constant in the
      cells and in the PSI complexes from logarithmic and stationary cell growth
      stages. We conclude that both 5'-monohydroxyphylloquinone and phylloquinone
      stably co-exist as major and minor naphthoquinones in Chlamydomonas PSI.

PMID- 22138101
TI  - Prognostic value of platelet count in diffuse large B-cell lymphoma.
AB  - BACKGROUND: Besides International Prognostic Index, many parameters have proven
      prognostic significance in aggressive lymphoma. However, the most appropriate
      system of risk stratification in diffuse large B-cell lymphoma (DLBCL) is not yet
      clear. In this study, we attempt to clarify the prognostic value of platelet
      count at the onset of lymphoma. MATERIALS AND METHODS: Between January 2000 and
      December 2009, 100 patients with DLBCL receiving R-CEOP (rituximab,
      cyclophosphamide, epirubicin, vincristine, and prednisolone) in a single
      institution were enrolled. Patient characteristics and survival outcomes were
      retrospectively analyzed. RESULTS: Before front-line treatment, 17 patients with
      thrombocytopenia (< 150 * 10(9)/L) and 83 patients without thrombocytopenia were
      enrolled. Thrombocytopenic patients initially presented with more B symptoms (P =
      .040), more bone marrow involvement (P = .001), later staging (P = .001), and
      higher International Prognostic Index (P < .001). Thrombocytopenia was shown to
      be an independently poor prognostic factor in the multivariate analysis of
      overall survival (hazard ratio [HR], 3.405; 95% confidence interval [CI], 1.431
      8.101; P = .006) and progression-free survival (HR, 4.299; 95% CI, 1.786-10.343;
      P = .001). CONCLUSION: Platelet count at diagnosis is a simple but useful
      indicator for predicting survival outcomes of DLBCL. Although the mechanisms of
      thrombocytopenia may be complex in lymphoma, further investigations are warranted
      to illustrate the predictive merit.

PMID- 22138103
TI  - A method for estimating normative distributions for study-specific populations of
      clinical trials.
AB  - For any particular psychological instrument, published normative distributions
      have been derived in one to at most a few specific "reference" populations. Here
      a method is provided for estimating a normative distribution pertinent to the
      specific population being evaluated in a randomized clinical trial. Normative
      quantiles are obtained using quantile regression, a method chosen for its
      flexibility in that no assumptions are made about the parametric form (e.g.,
      Gaussian) of the normative distribution to be estimated. Outcome is regressed on
      disease severity for the tauth quantile using that sample of consented
      participants who were not randomized because they fell below the trial's disease
      severity entry criterion. The tauth quantile of the normative distribution is
      then estimated by the intercept of this fitted regression function, which
      corresponds to severity of zero. Additional covariates that explain variation in
      outcome may be included to permit adjustment for shifts in their distributions
      between the randomized and non-randomized samples. The method is illustrated
      using data on a depression instrument (GRID Hamilton Rating Scale for Depression)
      and a neurocognitive instrument (CogScreen Pathfinder Number) from a multicenter
      clinical trial in sleep apnea patients.

PMID- 22138102
TI  - The reaction of HOCl and cyanocobalamin: corrin destruction and the liberation of
      cyanogen chloride.
AB  - Overproduction of hypochlorous acid (HOCl) has been associated with the
      development of a variety of disorders such as inflammation, heart disease,
      pulmonary fibrosis, and cancer through its ability to modify various
      biomolecules. HOCl is a potent oxidant generated by the myeloperoxidase-hydrogen
      peroxide-chloride system. Recently, we have provided evidence to support the
      important link between higher levels of HOCl and heme destruction and free iron
      release from hemoglobin and RBCs. Our current findings extend this work and show
      the ability of HOCl to mediate the destruction of metal-ion derivatives of
      tetrapyrrole macrocyclic rings, such as cyanocobalamin (Cobl), a common
      pharmacological form of vitamin B12. Cyanocobalamin is a water-soluble vitamin
      that plays an essential role as an enzyme cofactor and antioxidant, modulating
      nucleic acid metabolism and gene regulation. It is widely used as a therapeutic
      agent and supplement, because of its efficacy and stability. In this report, we
      demonstrate that although Cobl can be an excellent antioxidant, exposure to high
      levels of HOCl can overcome the beneficial effects of Cobl and generate
      proinflammatory reaction products. Our rapid kinetic, HPLC, and mass
      spectrometric analyses showed that HOCl can mediate corrin ring destruction and
      liberate cyanogen chloride (CNCl) through a mechanism that initially involves
      alpha-axial ligand replacement in Cobl to form a chlorinated derivative,
      hydrolysis, and cleavage of the phosphonucleotide moiety. Additionally, it can
      liberate free Co, which can perpetuate metal-ion-induced oxidant stress. Taken
      together, these results are the first report of the generation of toxic molecular
      products through the interaction of Cobl with HOCl.

PMID- 22138104
TI  - RXRalpha deletion and E6E7 oncogene expression are sufficient to induce cervical
      malignant lesions in vivo.
AB  - Cervical cancer is the second leading cause of cancer deaths among women
      worldwide. High-Risk-Human Papillomaviruses (HR-HPVs) play an important etiologic
      role in the development of carcinoma of the uterine cervix. However, host factors
      are important in determining the outcome of genital HPV infection as most
      cervical precancerous lesions containing HR-HPVs do not progress to invasive
      carcinomas. Retinoids, acting through nuclear receptors (RARs, RXRs), play a
      crucial role in cervix development and homeostasis regulating growth and
      differentiation of a wide variety of cell types; indeed, they can inhibit cell
      proliferation, and induce cell differentiation or apoptotic cell death. Here we
      introduce a mouse model that develops spontaneously malignant cervical lesions
      allowing the study of the cooperative effect between HPV16E6E7 expression and the
      lack of RXRalpha in cervical cancer development. This model could be useful to
      study multistep carcinogenesis of uterine cervix tissue and might improve
      chemopreventive and chemotherapeutic strategies for this neoplasia.

PMID- 22138105
TI  - On the pulmonary toxicity of oxygen. 4. The thyroid arena.
AB  - Normally developed thyroid function is critical to the transition from fetal to
      neonatal life with the onset of independent thermoregulation, the most
      conspicuous of the many ways in which thyroid secretions act throughout the body.
      A role for thyroid secretions in growth and maturation of the lungs as part of
      the preparation for the onset of breathing has been recognized for some time but
      how this contributes to tissue and cell processes and defenses under the duress
      of respiratory distress has not been well examined. Extensive archival autopsy
      material was searched for thyroid and adrenal weights, first by gestational age,
      and then for changes during the first hours after birth as ratios to body weight.
      After a gestational age of 22 weeks the fetal thyroid and adrenal glands at
      autopsy in those with hyaline membrane disease are persistently half the size of
      those in "normal" infants dying with other disorders. When the thyroid is
      examined shortly after birth it reveals a post natal loss of mass per body weight
      of similar orders of magnitude which does not occur in the control group. A
      clinical sample of premature infants with (12) and without (14) hyaline membrane
      disease was tested for T(4), TSH, TBG, and total serum protein. The results also
      demonstrate a special subset with lower birth weights at the same gestational
      age, and lower serum T(4) and total serum protein. Ventilatory distress in
      newborn rabbits was induced by bilateral cervical vagotomy at 24 h post natal
      following earlier injection of thyroxine (T(4)) or thyroid stimulating hormone
      (TSH) and comparisons were made with untreated animals and by dose. Early life
      thyroidectomy was performed followed by exposure to either air or 100% oxygen. A
      final experiment in air was vagotomy after thyroidectomy. Composite analysis of
      these methods indicates that thyroid factors are both operative and important in
      the newborn animal with ventilatory distress. This work and the archival data
      indicate those infants destined to develop hyaline membrane disease through
      respiratory distress are a distinct developmental and clinical subset with the
      point of departure from otherwise normal development and maturation in the second
      or early third trimester. This interval is known to be a period of marked
      variation in the overview indicators of fetal progress through gestational time.
      The initiating factor or circumstance which then separates this special subset
      from normal future development is placed by these observations firmly into the
      period when human fetal TSH dramatically rises 7-fold (17.5-25.5 weeks) followed
      by a lesser 3 to 4-fold increase in T(4) which is extended into the early third
      trimester. The earlier part of this interval is characterized by the thyrotrophic
      action of chorionic gonadotropin (hCG). The possibility that abnormalities in the
      intrauterine environment secondary to maternal infection play a role within this
      time frame is indicated by the demonstration that interleukin-2 (IL-2) induces an
      anterior pituitary release of TSH. Since IL-2 has this property and is not an
      acute phase cytokine, some form of chronic infection or an immunopathic process
      seems more likely as a possible active factor in pathogenesis.

PMID- 22138106
TI  - Effects of a peripheral cholinesterase inhibitor on cytokine production and
      autonomic nervous activity in a rat model of sepsis.
AB  - PURPOSE: Recently, cholinergic anti-inflammatory pathway manipulation has been
      proposed as a new strategy to control cytokine production in sepsis. We
      investigated whether hypercytokinemia can be controlled via this pathway in an
      animal model of sepsis, with concomitant monitoring of autonomic nervous activity
      involving heart rate variability (HRV) analysis of electrocardiographic R-R
      intervals. METHODS: Sixty-eight adult male Sprague-Dawley rats were used (28 for
      examination of cytokine production and autonomic nervous activity; 40 for
      survival analysis). Each part of the study involved four animal groups, including
      two control groups without drug administration. Sepsis was induced by cecal
      ligation and puncture (CLP). Distigmine bromide, a peripheral, non-selective
      cholinesterase inhibitor (0.01mg/kg), was administered subcutaneously 90 min
      after surgery. Continuous electrocardiograms were recorded for 5 min before and
      after surgery (at intervals of 5h) in CLP and sham-operated animals for HRV
      analysis. Blood samples were collected 20 h after surgery for serum cytokine and
      catecholamine assay. RESULTS: On HRV analysis, distigmine inhibited reduction of
      total power and high-frequency components in CLP animals (P<0.05). Distigmine
      significantly inhibited cytokine induction (IL-6 and IL-10) (P<0.01) as well as
      increase in serum levels of noradrenaline and dopamine (P<0.05). Distigmine did
      not significantly improve CLP animal survival rate. CONCLUSIONS: The
      cholinesterase inhibitor distigmine inhibited induction of inflammatory cytokines
      and catecholamines as well as HRV suppression in a rat CLP model, suggesting that
      an agent modulating the cholinergic anti-inflammatory pathway can control excess
      cytokine production involved in the pathogenesis of severe sepsis/septic shock.

PMID- 22138107
TI  - TNF-alpha induced NFkappaB signaling and p65 (RelA) overexpression repress Cldn5
      promoter in mouse brain endothelial cells.
AB  - Inflammatory cytokine TNFalpha enhances permeability of brain capillaries
      constituting blood brain barrier (BBB). In the monoculture endothelial models of
      BBB TNFalpha alters tight junction (TJ) structure and protein content. Claudin-5
      (Cldn5) is a key TJ protein whose expression in the brain endothelial cells is
      critical to the function of BBB. TNFalpha reduces Cldn5 promoter activity and
      mRNA expression in mouse brain derived endothelial cells but the regulatory
      elements and signaling mechanism involved are not defined. Here we report that
      TNFalpha acts through NFkappaB signaling and requires a conserved promoter region
      for the down-regulation of Cldn5 expression. Overexpression of the NFkappaB
      subunit p65 (RelA) alone repressed Cldn5 promoter activity in mouse brain
      endothelial cells. We observed partial loss of Cldn5 protein expression after
      prolonged TNFalpha treatment in primary endothelial culture isolated from C56BL/6
      mice brain. Taken together, our results confirm and extend previous observations
      of TNFalpha induced down-regulation of Cldn5 expression in mouse brain
      endothelial cells.

PMID- 22138108
TI  - Structural bases of Wolman disease and cholesteryl ester storage disease.
AB  - To elucidate the bases of Wolman disease (WD) and cholesteryl ester storage
      disease (CESD) from the viewpoint of enzyme structure, we constructed a
      structural model of human lysosomal acid lipase (LAL) using molecular modeling
      software Modeller. The results revealed that the residues responsible for WD/CESD
      tend to be less solvent-accessible than others. Then, we examined the structural
      changes in the LAL protein caused by the WD/CESD mutations, using molecular
      modeling software TINKER. The results indicated that conformational changes of
      the functionally important residues and/or large conformational changes tend to
      cause the severe clinical phenotype (WD), whereas small conformational changes
      tend to cause the mild clinical phenotype (CESD), although there have been
      several exceptions. Further structural analysis is required to clarify the
      relationship between the three-dimensional structural changes and clinical
      phenotypes.

PMID- 22138109
TI  - Treatment of full-thickness chondral defects of the knee with autologous
      chondrocyte implantation: a functional evaluation with long-term follow-up.
AB  - BACKGROUND: Autologous chondrocyte implantation (ACI) has been proven an
      effective method in treating large articular cartilage defects in short- or
      medium-term follow-up clinical studies. HYPOTHESIS: First generation ACI of
      patients with large full-thickness chondral defects of the knee could yield
      reliable functional outcomes after a minimum follow-up of 5 years. STUDY DESIGN:
      Case series; Level of evidence, 4. METHODS: Between 1997 and 2005, 42 patients
      (45 knees) underwent first generation ACI for symptomatic chondral defects of the
      knee. All patients had moderate to large (mean, 5.33 cm(2)) full-thickness
      chondral defects. Patients were evaluated using the International Cartilage
      Repair Society (ICRS) score, the International Knee Documentation Committee
      (IKDC) Knee Examination Form, the Tegner activity score, the Lysholm score, the
      Stanmore functional rating score, and a visual analog scale (VAS) for pain.
      RESULTS: The mean follow-up was 96 months (range, 62-144 months). At the final
      follow-up, a significant increase in all scores was recorded. Compared with
      preoperative findings, the median Lysholm score significantly improved,
      increasing from 56.0 to 89.0 (P < .05). The IKDC and the Tegner activity score
      showed significant improvement postoperatively, increasing from 45 and 5.5 to 69
      and 6.5, respectively (P < .05). The mean ICRS improved from grade 3.8
      preoperatively to grade 2.8 postoperatively (P < .05). The Stanmore functional
      rating score and the VAS pain score were decreased from 3.06 and 7.33 to 0.94 and
      2, respectively (P < .05). Reoperation was required in 5 patients. In 2 of them
      graft failure was recorded due to degeneration or partial detachment,
      respectively. CONCLUSION: The long-term outcomes of our series support the
      effectiveness of first generation ACI in both pain relief and functional
      rehabilitation of patients with large full-thickness osteochondral defects of the
      knee.

PMID- 22138110
TI  - Open lateral retinacular closure surgery for treatment of anterolateral knee pain
      and disability after arthroscopic lateral retinacular release.
AB  - BACKGROUND: Although lateral retinacular release (LR) surgery has historically
      been one of the most commonly used arthroscopic procedures for the treatment of
      patellar instability and anterior knee pain, it may be associated with
      complications and poor functional outcome measures. PURPOSE: To examine the
      clinical efficacy of open lateral retinacular closure (LRC), a novel but
      technically simple procedure in the treatment of disabling anterolateral knee
      pain, tenderness, and positive medial patellar apprehension testing in patients
      who have undergone prior arthroscopic LR surgery. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: The records of 22 patients who had previously
      undergone an arthroscopic LR and underwent a diagnostic arthroscopy and LRC were
      reviewed. Physical examination findings and symptoms after prior LR surgery,
      duration between LR and LRC surgeries, and arthroscopic findings immediately
      before LRC were analyzed. Preoperative and postoperative Lysholm knee scores and
      activity levels were compared, and subjective satisfaction ratings assessed.
      RESULTS: Average follow-up after LRC was 3.2 years. Mean preoperative Lysholm
      knee score was 46.5 (range, 25-90), which improved postoperatively to a mean
      score of 86 (range, 48-100). Fourteen percent of patients subjectively rated
      their preoperative function as fair and 86% as poor. Postoperatively, 82% rated
      themselves as good or excellent and 18% as fair, with all patients improving from
      the LRC procedure. All patients stated that they would have the procedure again
      for the same problem. CONCLUSION: Open LRC provides significant pain relief and
      improvement in functional knee outcome scores in patients with persistent pain
      and tenderness at the site of a previous lateral release and a positive medial
      patellar apprehension test. Lateral release procedures should be considered with
      caution. For patients with anterolateral knee pain and symptoms of medial
      patellar instability after lateral release, LRC may provide symptomatic relief
      and functional improvement.

PMID- 22138111
TI  - Molecular mechanisms of pituitary endocrine cell calcium handling.
AB  - Endocrine pituitary cells express numerous voltage-gated Na(+), Ca(2+), K(+), and
      Cl(-) channels and several ligand-gated channels, and they fire action potentials
      spontaneously. Depending on the cell type, this electrical activity can generate
      localized or global Ca(2+) signals, the latter reaching the threshold for
      stimulus-secretion coupling. These cells also express numerous G-protein-coupled
      receptors, which can stimulate or silence electrical activity and Ca(2+) influx
      through voltage-gated Ca(2+) channels and hormone release. Receptors positively
      coupled to the adenylyl cyclase signaling pathway stimulate electrical activity
      with cAMP, which activates hyperpolarization-activated cyclic nucleotide
      regulated channels directly, or by cAMP-dependent kinase-mediated phosphorylation
      of K(+), Na(+), Ca(2+), and/or non-selective cation-conducting channels.
      Receptors that are negatively coupled to adenylyl cyclase signaling pathways
      inhibit spontaneous electrical activity and accompanied Ca(2+) transients
      predominantly through the activation of inwardly rectifying K(+) channels and the
      inhibition of voltage-gated Ca(2+) channels. The Ca(2+)-mobilizing receptors
      activate inositol trisphosphate-gated Ca(2+) channels in the endoplasmic
      reticulum, leading to Ca(2+) release in an oscillatory or non-oscillatory manner,
      depending on the cell type. This Ca(2+) release causes a cell type-specific
      modulation of electrical activity and intracellular Ca(2+) handling.

PMID- 22138112
TI  - Effects of eHealth interventions on medication adherence: a systematic review of
      the literature.
AB  - BACKGROUND: Since medication nonadherence is considered to be an important health
      risk, numerous interventions to improve adherence have been developed. During the
      past decade, the use of Internet-based interventions to improve medication
      adherence has increased rapidly. Internet interventions have the potential
      advantage of tailoring the interventions to the needs and situation of the
      patient. OBJECTIVE: The main aim of this systematic review was to investigate
      which tailored Internet interventions are effective in improving medication
      adherence. METHODS: We undertook comprehensive literature searches in PubMed,
      PsycINFO, EMBASE, CINAHL, and Communication Abstracts, following the guidelines
      of the Cochrane Collaboration. The methodological quality of the randomized
      controlled trials and clinical controlled trials and methods for measuring
      adherence were independently reviewed by two researchers. RESULTS: A total of 13
      studies met the inclusion criteria. All included Internet interventions clearly
      used moderately or highly sophisticated computer-tailored methods. Data synthesis
      revealed that there is evidence for the effectiveness of Internet interventions
      in improving medication adherence: 5 studies (3 high-quality studies and 2 low
      quality studies) showed a significant effect on adherence; 6 other studies (4
      high-quality studies and 2 low-quality studies) reported a moderate effect on
      adherence; and 2 studies (1 high-quality study and 1 low-quality study) showed no
      effect on patients' adherence. However, most studies used self-reported
      measurements to assess adherence, which is generally perceived as a low-quality
      measurement. In addition, we did not find a clear relationship between the
      quality of the studies or the level of sophistication of message tailoring and
      the effectiveness of the intervention. This might be explained by the great
      difference in study designs and the way of measuring adherence, which makes
      results difficult to compare. There was also large variation in the measured
      interval between baseline and follow-up measurements. CONCLUSION: This review
      shows promising results on the effectiveness of Internet interventions to enhance
      patients' adherence to prescribed long-term medications. Although there is
      evidence according to the data synthesis, the results must be interpreted with
      caution due to low-quality adherence measurements. Future studies using high
      quality measurements to assess medication adherence are recommended to establish
      more robust evidence for the effectiveness of eHealth interventions on medication
      adherence.

PMID- 22138113
TI  - Utilization characteristics of spinal interventions.
AB  - BACKGROUND CONTEXT: Several investigators have identified an explosive increase
      in spinal injection rates in the Veterans Administration and Medicare
      populations. Furthermore, utilization of spinal injection procedures appears to
      vary by geographic location, subspecialty, and practice setting. Medicare claims
      analysis has shown that a small percentage of physicians perform a
      disproportionately large number of injections. Although Medicare utilization has
      been well characterized, the utilization patterns for privately insured
      individuals are not clearly known. PURPOSE: The primary purpose of this article
      was to investigate whether relatively few providers are responsible for a
      disproportionately high percentage of interventional spine procedures in
      privately insured plans and to quantify any such findings. The secondary purpose
      was to determine if provider specialty is a relevant variable in any identified
      patterns of disproportionate utilization. STUDY DESIGN: A descriptive analysis of
      utilization patterns using the Medstat MarketScan database was conducted between
      2003 and 2007. The database contains deidentified medical, pharmacy, and
      enrollment claims representing 12 to 14 million individuals. PATIENT SAMPLE: A
      data set was generated based on the following inclusion criteria: all patients
      aged between 18 and 99 years receiving at least one spinal interventional
      procedure between 2003 and 2007: epidural steroid injections, intra-articular
      facet or medial branch blocks, medial branch radio frequency neurotomy,
      sacroiliac joint injections, and discography. Our inclusion criteria yielded data
      on nearly 200,000 patients treated by over 20,000 providers. OUTCOME MEASURES:
      Not applicable. METHODS: The number of procedures was tallied for a 12-month
      period beginning with a patient's first procedure claim. The total number of
      procedures per patient and the mean number of procedures per patient were
      calculated for the study sample. Within each specialty, all spinal procedures
      were summed for each individual provider within each procedure category and as an
      overall total. The overall mean number of therapeutic procedures per patient for
      all physicians within a specialty was calculated. Within each specialty, the
      total number of procedures performed by each physician was analyzed in
      percentiles to highlight any disparity between high- and low-using providers.
      RESULTS: The final therapeutic procedure data set contained 196,332 patients who
      received 875,627 procedures. The principal nine specialties performing these
      procedures were anesthesiology (49.2% of the total number of procedures in the
      final data set), physiatry (12.5%), pain management (12.0%), family practice
      (10.2%), orthopedics (5.5%), radiology (3.0%), neurology (2.8%), internal
      medicine (2.8%), and neurosurgery (1.9%). The overall mean number of procedures
      across all categories performed per patient during the 12-month inclusion period
      was 4.46+/-6.44. Neurologists and pain management specialists were the only
      provider groups in which the mean number of procedures per patient exceeded the
      overall mean. The highest 10% of providers, which encompasses those providers
      performing a mean greater than or equal to 5.08 procedures per patient per year,
      perform 36.6% of the total spinal procedures performed. The highest 20% of
      providers, which encompasses those providers with a mean greater than or equal to
      3.75, account for 57.6% of all spinal procedures. The highest 10% of providers
      perform nine times more procedures per patient compared with the lowest 10% and
      4.5 times more procedures than the median. This same pattern of high utilization
      by disproportionately few providers was observed across all nine specialties.
      CONCLUSIONS: These findings demonstrate that relatively few providers are
      responsible for a disproportionately high percentage of interventional spine
      procedures. This pattern of marked overutilization by a minority of providers is
      the dominant characteristic of utilization within all specialties.

PMID- 22138114
TI  - Mere exposure to palatable food cues reduces restrained eaters' physical effort
      to obtain healthy food.
AB  - We examined whether exposure to cues of attractive food reduces effortful
      behavior toward healthy foods for restrained eaters. After manipulating food pre
      exposure, we recorded handgrip force while presenting participants with pictures
      of healthy food objects. Because participants were led to expect that they could
      obtain each object (not specified beforehand) by squeezing the handgrip as
      forcefully as possible while the object was displayed on the screen, the recorded
      handgrip force constitutes a measure of spontaneous effortful behavior. Results
      show that restrained eaters, but not unrestrained eaters, displayed less forceful
      action toward healthy food objects (i.e., lower exertion of force) when pre
      exposed to tempting food cues. No effects were found on palatability perceptions
      of the healthy foods. The results provide further insight into why restrained
      eaters have difficulties in maintaining a low-calorie diet in food-rich
      environments.

PMID- 22138115
TI  - Reflective and impulsive influences on unhealthy snacking. The moderating effects
      of food related self-control.
AB  - This study proposes that snacking behaviour may be either reflective and
      deliberate or impulsive, thus following a dual-process account. We hypothesised
      that chronic individual differences in food related self-control would moderate
      the relationships between reflective and impulsive processes. The reflective
      route was represented by an attitude toward unhealthy snacking, while the
      impulsive route was represented by the tendency to buy snack on impulse. A web
      survey was conducted with 207 students and employees at a Norwegian university,
      and a moderated hierarchical regression analysis using structural equation
      modelling was used to estimate the theoretical model. The findings showed that
      both attitudes towards unhealthy snacking and impulsive snack buying tendency
      were positively related to snack consumption. Food related self-control moderated
      the relation between attitude and behaviour, as well as the relation between
      impulsive snack buying tendency and behaviour. The effect of attitude on
      consumption was relatively strong when food related self-control was strong,
      while the effect of impulsive snack buying on consumption was relatively strong
      when food related self-control was weak. The results thus suggest that while weak
      self-control exposes individuals vulnerable to impulsive tendencies, strong self
      control does not necessarily lead to less unhealthy snacking, but this depends on
      the valence of an individual's attitude.

PMID- 22138116
TI  - A novel fluorescent nanoparticle composed of fluorene copolymer core and silica
      shell with enhanced photostability.
AB  - A variety of fluorescent nanoparticles have been developed for demanding
      applications such as optical biosensing and fluorescence imaging in live cells.
      Silica-based fluorescent nanoparticles offer diverse advantages for biological
      applications. For example, they can be used as labeling probes due to their low
      toxicity, high sensitivity, resolution, and stability. In this research, a new
      class of highly fluorescent, efficient nanoparticles composed of a newly
      synthesized poly[di(2-methoxy-5-(2-ethylhexyloxy))-2,7-(9,9-dioctyl-9H-fluorene)]
      (PDDF) core and a silica shell (designated as PDDF@SiO(2)) were prepared using a
      simple reverse micelle method, and their fluorescent properties were evaluated
      using methods such as single-dot photoluminescence measurements. The enhanced
      photostability of the particles and their potential applications for bioanalysis
      are discussed in this article. The morphology, size, and fluorescent properties
      for prepared PDDF@SiO(2) nanoparticles were characterized using transmission
      electron microscopy (TEM), scanning electron microscopy (SEM) and
      photoluminescence spectroscopy. The prepared particles size, which was
      approximately 60 nm, resulted in an excellent colloidal stability in a
      physiological environment. The photobleaching dynamics, total numbers of emitted
      photons (TNEP) and statistical measurements of individual nanoparticles were
      observed using laser scanning fluorescence microscopy to assess the structure and
      photostability of PDDF@SiO(2) nanoparticles. Additionally, PDDF@SiO(2)
      nanoparticles were used in cell toxicity and permeation tests for biological
      analyses, demonstrating a great potential for use as powerful, novel materials
      within the emerging fields of biosensing and biomedical engineering.

PMID- 22138117
TI  - A smart dynamic self-induced orientable multiple size nano-roughness with
      amphiphilic feature as a stain-repellent hydrophilic surface.
AB  - Recently developing bioinspired super-hydrophobic surfaces to achieve self
      cleaning properties has been driving numerous researches. However, hydrophilicity
      is one of the most important features of garment comfort. Therefore,
      accomplishing self-cleaning and stain repellency on hydrophilic surfaces would be
      a high topic of interest. This research is concerned with wettability mechanism;
      static and dynamic study of contact angle through water droplet absorption on the
      multiple scale nano-roughness covered by different weight ratio of oppositely
      charged inorganic nanoparticles and amino-functionalized polysiloxane. The
      results revealed that the second layer of the resin formed on the surface can
      show an amphiphilic hybrid block copolymer-like feature whose dual action can be
      intensified during water droplet absorption by the created multiple size nano
      roughness. This unique structure can create a stain repellent but hydrophilic
      surface with exceptional advantages. The mechanism has been deeply discussed
      according to the evidence on droplet edge interfacial energy changes as a driving
      force to overcome meta-stable Cassie state on the multiple size nano-roughness
      with amphiphilic feature. A lotus-like nano-roughness has been also observed on
      the SEM micrographs. Based on a statistically approached experimental design, the
      effect of variant factors on droplet absorption time, static, advancing, receding
      contact angles and self-cleaning properties has been mathematically modeled
      according to the response surface methodology (RSM).

PMID- 22138118
TI  - Minor salivary gland tumors in the oral cavity: diagnostic value of dynamic
      contrast-enhanced MRI.
AB  - OBJECTIVE: To evaluate the diagnostic value of dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) for minor salivary gland tumors in the oral cavity.
      MATERIALS AND METHODS: Thirty-two patients with minor salivary gland tumors were
      examined preoperatively using DCE-MRI. Their maximum contrast index (CImax), time
      of CImax (Tmax), Tpeak; i.e., the time that corresponded to the CImax*0.90, and
      washout ratios (WR300 and WR600) were determined from contrast index (CI) curves.
      We compared these parameters between benign and malignant tumors and among the
      different histopathological types of minor salivary gland tumors. Then, we
      categorized the patients' CI curves into four patterns (gradual increase, rapid
      increase with high washout ratio, rapid increase with low washout, and flat).
      RESULTS: Statistically significant differences in Tmax (P=0.004) and Tpeak
      (P=0.002) were observed between the benign and malignant tumors. Regarding each
      histopathological tumor type, significant differences in Tmax (P<0.001), Tpeak
      (P<0.001), and WR600 (P=0.026) were observed between the pleomorphic adenomas and
      mucoepidermoid carcinomas. It was difficult to distinguish between benign and
      malignant tumors using our CI curve classification because that two-thirds of the
      cases were classified into the same type (gradual increase). CONCLUSION: The DCE
      MRI parameters of minor salivary gland tumors contributed little to their
      differential diagnosis compared with those for major salivary gland tumors.
      During the diagnosis of minor salivary gland tumors, Tmax is useful for
      distinguishing between benign and malignant tumors.

PMID- 22138119
TI  - Optimisation of T2*-weighted MRI for the detection of small veins in multiple
      sclerosis at 3 T and 7 T.
AB  - T2*-weighted magnetic resonance imaging at 7 T has recently been shown to allow
      differentiation between white-matter multiple sclerosis lesions and asymptomatic
      white-matter lesions, by the presence or absence of a detectable central blood
      vessel. The aim of the present work is to improve the technique by increasing the
      sensitivity to veins at both 3 T and 7 T, and to assess the benefit of ultra-high
      field imaging. Signal-to-noise ratio (SNR) measurements and simulations are used
      to compare the sensitivity of magnitude T2*-weighted and susceptibility-weighted
      images for the detection of small veins (<1 pixel in diameter), both with and
      without the use of gadolinium. The simulations are used to predict the optimal
      scanning parameters in order to increase the sensitivity to these veins at both
      field strengths, and to reduce the inherent dependence on vessel orientation. The
      sensitivities of the sequences at both field strengths are compared,
      theoretically and experimentally, in order to quantify the benefit of imaging at
      ultra-high-field. Subjects with multiple sclerosis (MS) are scanned at both field
      strengths, using the optimised sequence parameters, as well as those used in
      previously published work, and the optimisation is shown to improve the detection
      of veins within lesions.

PMID- 22138120
TI  - High-resolution functional MRI of the human amygdala at 7 T.
AB  - Functional magnetic resonance imaging (fMRI) has become the primary non-invasive
      method for investigating the human brain function. With an increasing number of
      ultra-high field MR systems worldwide possibilities of higher spatial and
      temporal resolution in combination with increased sensitivity and specificity are
      expected to advance detailed imaging of distinct cortical brain areas and
      subcortical structures. One target region of particular importance to
      applications in psychiatry and psychology is the amygdala. However, ultra-high
      field magnetic resonance imaging of these ventral brain regions is a challenging
      endeavor that requires particular methodological considerations. Ventral brain
      areas are particularly prone to signal losses arising from strong magnetic field
      inhomogeneities along susceptibility borders. In addition, physiological
      artifacts from respiration and cardiac action cause considerable fluctuations in
      the MR signal. Here we show that, despite these challenges, fMRI data from the
      amygdala may be obtained with high temporal and spatial resolution combined with
      increased signal-to-noise ratio. Maps of neural activation during a facial
      emotion discrimination paradigm at 7 T are presented and clearly show the gain in
      percental signal change compared to 3T results, demonstrating the potential
      benefits of ultra-high field functional MR imaging also in ventral brain areas.

PMID- 22138121
TI  - Real-time elastography for the differentiation of benign and malignant
      superficial lymph nodes: a meta-analysis.
AB  - BACKGROUND: Real-time elastography (RTE), as a non-invasive method, is used for
      the classification of benign and malignant lymph nodes (LNs) and developed as an
      alternative to biopsy. Elasticity score (ES) and strain ratio (SR) are used for
      the interpretation of RTE. We studied the performance of RTE for diagnosis of
      malignant LNs using meta-analysis. METHODS: PubMed, the Cochrane Library, ISI Web
      of Knowledge, China National Knowledge Infrastructure were searched. The studies
      published in English or Chinese relating to the diagnostic value of RTE for
      superficial LNs were collected. Hierarchical summary receiver operating
      characteristic (HSROC) curve was used to examine the RTE accuracy. Clinical
      utility of RTE for LNs was evaluated by Fagan plot analysis. RESULTS: A total of
      9 studies which included 835 LNs were analyzed. The summary sensitivity and
      specificity for the diagnosis of malignant LNs were 0.74 (95% confidence interval
      (CI), 0.66-0.81) and 0.90 (95% CI, 0.82-0.94) for ES, and 0.88 (95% CI, 0.79
      0.93) and 0.81 (95% CI, 0.49-0.95) for SR, respectively. Compared to ES, SR
      obviously improved the diagnostic sensitivity value. The HSROCs were 0.88 for ES
      and 0.91 for SR, respectively. After RTE results over the cut-off value for
      malignant LNs ("positive" result), the corresponding post-test probability for
      the presence (if pre-test probability was 50%) was 88% for ES and 82% for SR,
      respectively; while, in "negative" measurement, the post-test probability was 22%
      and 13%, respectively. CONCLUSION: RTE has a high accuracy in the classification
      of superficial LNs and can potentially help to select suspicious LNs for biopsy.

PMID- 22138122
TI  - Hepatic hemangiomas: difference in enhancement pattern on 3T MR imaging with
      gadobenate dimeglumine versus gadoxetate disodium.
AB  - PURPOSE: To compare intraindividual differences in enhancement pattern of hepatic
      hemangiomas between gadobenate dimeglumine (Gd-BOPTA) and gadoxetate disodium (Gd
      EOB-DTPA)-enhanced 3T MR imaging. MATERIALS AND METHODS: This is a HIPAA
      compliant, IRB-approved retrospective study with waiver for informed consent
      granted. From 10/07 to 5/09, 10 patients (2 males, 8 females; mean age, 57.3
      years) with 15 hepatic hemangiomas (mean diameter, 4.4 +/- 5.6 cm) underwent both
      Gd-BOPTA- and Gd-EOB-DTPA-enhanced 3T MR imaging (mean interval, 266 days; range,
      38-462 days). Diagnosis of hemangioma was based on strict imaging criteria. MR
      imaging was obtained during three arterial, portal venous, and up to four delayed
      phases. During each phase, hemangioma-to-liver contrast-to-noise ratio (CNR) was
      measured for each lesion on both examinations. Statistical analysis was performed
      using paired Student's t-test. RESULTS: Hemangioma-to-liver CNR peaked during the
      portal venous phase (Gd-BOPTA: 48.9 +/- 65.8, Gd-EOB-DTPA: 0.7 +/- 3.8). During
      all imaging phases except the first arterial phase, hemangioma-to-liver CNR was
      significantly lower on Gd-EOB-DTPA-enhanced compared to Gd-BOPTA-enhanced MR
      images (p<0.05). Notably, Gd-EOB-DTPA yielded negative hemangioma-to-liver CNR (
      2.5 +/- 2.4) compared to Gd-BOPTA (40.7 +/- 56.4) during the first delayed phase
      (7-8 min after contrast administration), remaining negative for the rest of the
      delayed phases (up to 26 min after contrast administration). CONCLUSION: The
      enhancement patterns of hepatic hemangiomas differs significantly between Gd
      BOPTA and Gd-EOB-DTPA-enhanced 3T MR imaging. The smaller dose, shorter plasma
      half-life, and increased hepatobiliary uptake of Gd-EOB-DTPA leads to a negative
      CNR of hemangioma-to-liver on delayed phases and could create an imaging pitfall
      with this agent.

PMID- 22138123
TI  - Differential gene expression analysis in fracture callus of patients with regular
      and failed bone healing.
AB  - OBJECTIVE: Although several systemic and local factors are known to impair
      fracture healing, there is still no explanation, why some patients with
      sufficient fracture stability, showing none of the existing risk factors, still
      fail to heal normally. An investigation of local gene expression patterns in the
      fracture gap of patients with non-unions could decisively contribute to a better
      understanding of the pathophysiology of impaired fracture healing. For the first
      time, this study compares the expression of a large variety of osteogenic and
      chondrogenic genes in patients with regular and failed fracture healing. METHODS:
      Between March 2006 and May 2007, a total of 130 patients who were surgically
      treated at the Berufsgenossenschaftliche Unfallklink Ludwigshafen were screened
      for the study. Tissue samples of patients with normal and failed fracture healing
      were collected intraoperatively. Patients were divided into groups depending on
      the fracture date, and only patients with fractures two to four weeks old and
      patients with non-unions more than 9 months old were included in the final
      analysis. For the gene expression analysis, a customised cDNA array - containing
      226 genes involved in osteo- and chondrogenesis - was used. RESULTS: In the cDNA
      array analysis, the expression of eight genes was significantly elevated two-fold
      or more in the group with failed fracture healing relative to the normal
      controls. Conversely, no genes were found to be expressed at a higher level in
      the control group. The identified genes are supposed to be involved in
      extracellular matrix assembly, cytoskeletal structure, and differentiative and
      proliferative processes. CONCLUSIONS: The differences in gene expression pattern
      indicate a change in the composition and structure of the extracellular matrix,
      and a possible turn in the healing programme towards fibrous scar tissue
      formation, leading to non-union.

PMID- 22138124
TI  - Air sampling methods to evaluate microbial contamination in operating theatres:
      results of a comparative study in an orthopaedics department.
AB  - AIM: To evaluate the level of microbial contamination of air in operating
      theatres using active [i.e. surface air system (SAS)] and passive [i.e. index of
      microbial air contamination (IMA) and nitrocellulose membranes positioned near
      the wound] sampling systems. METHODS: Sampling was performed between January 2010
      and January 2011 in the operating theatre of the orthopaedics department in a
      university hospital in Southern Italy. FINDINGS: During surgery, the mean
      bacterial loads recorded were 2232.9 colony-forming units (cfu)/m(2)/h with the
      IMA method, 123.2 cfu/m(3) with the SAS method and 2768.2 cfu/m(2)/h with the
      nitrocellulose membranes. Correlation was found between the results of the three
      methods. Staphylococcus aureus was detected in 12 of 60 operations (20%) with the
      membranes, five (8.3%) operations with the SAS method, and three operations (5%)
      with the IMA method. CONCLUSION: Use of nitrocellulose membranes placed near a
      wound is a valid method for measuring the microbial contamination of air. This
      method was more sensitive than the IMA method and was not subject to any
      calibration bias, unlike active air monitoring systems.

PMID- 22138125
TI  - The time course of symbolic number adaptation: oscillatory EEG activity and event
      related potential analysis.
AB  - Several functional magnetic resonance imaging (fMRI) studies have used neural
      adaptation paradigms to detect anatomical locations of brain activity related to
      number processing. However, currently not much is known about the temporal
      structure of number adaptation. In the present study, we used
      electroencephalography (EEG) to elucidate the time course of neural events in
      symbolic number adaptation. The numerical distance of deviants relative to
      standards was manipulated. In order to avoid perceptual confounds, all levels of
      deviants consisted of perceptually identical stimuli. Multiple successive
      numerical distance effects were detected in event-related potentials (ERPs).
      Analysis of oscillatory activity further showed at least two distinct stages of
      neural processes involved in the automatic analysis of numerical magnitude, with
      the earlier effect emerging at around 200ms and the later effect appearing at
      around 400ms. The findings support for the hypothesis that numerical magnitude
      processing involves a succession of cognitive events.

PMID- 22138126
TI  - Localization of nerve growth factor (NGF) receptors in the mitochondrial
      compartment: characterization and putative role.
AB  - BACKGROUND: The neurotrophin NGF receptors trkA and p75NTR are expressed in the
      central and peripheral nervous system as well as in non-neuronal tissues;
      originally described to localize to the plasma membrane, recent studies have
      suggested other intracellular localizations for both NGF receptors. SCOPE OF
      REVIEW: In order to determine whether NGF receptors localize to the mitochondrial
      compartment mitochondria isolated from human kidney, rat tissues and a human
      podocyte as cell line before and after differentiation were used. MAJOR
      CONCLUSIONS: Our results demonstrate that NGF receptors are localized in the
      mitochondrial compartment of undifferentiated human podocytes and in all tissues
      analyzed including rat central nervous system. In mitochondria p75NTR, but not
      trkA, co-immunoprecipitates with the adenine nucleotide translocator (ANT) and
      the phosphodiesterase 4 isoform A5 (PDE4A5). Moreover, NGF, via trkA, protects
      isolated mitochondria of rat brain cortex from mitochondrial permeability
      transition induced by Ca(2+). GENERAL SIGNIFICANCE: Although NGF receptors have
      been described as mainly citoplasmatic so far, we proved evidence of their
      expression at the mitochondrial level and their interaction with specific
      proteins. Our results demonstrating the expression of NGF receptors in the
      mitochondria provide new insights into the role of NGF at subcellular level, in
      different areas of the organism, including CNS.

PMID- 22138127
TI  - Beyond readability: investigating coherence of clinical text for consumers.
AB  - BACKGROUND: A basic tenet of consumer health informatics is that understandable
      health resources empower the public. Text comprehension holds great promise for
      helping to characterize consumer problems in understanding health texts. The need
      for efficient ways to assess consumer-oriented health texts and the availability
      of computationally supported tools led us to explore the effect of various text
      characteristics on readers' understanding of health texts, as well as to develop
      novel approaches to assessing these characteristics. OBJECTIVE: The goal of this
      study was to compare the impact of two different approaches to enhancing
      readability, and three interventions, on individuals' comprehension of short,
      complex passages of health text. METHODS: Participants were 80 university staff,
      faculty, or students. Each participant was asked to "retell" the content of two
      health texts: one a clinical trial in the domain of diabetes mellitus, and the
      other typical Visit Notes. These texts were transformed for the intervention arms
      of the study. Two interventions provided terminology support via (1) standard
      dictionary or (2) contextualized vocabulary definitions. The third intervention
      provided coherence improvement. We assessed participants' comprehension of the
      clinical texts through propositional analysis, an open-ended questionnaire, and
      analysis of the number of errors made. RESULTS: For the clinical trial text, the
      effect of text condition was not significant in any of the comparisons,
      suggesting no differences in recall, despite the varying levels of support
      (P=.84). For the Visit Note, however, the difference in the median total
      propositions recalled between the Coherent and the (Original+Dictionary)
      conditions was significant (P=.04). This suggests that participants in the
      Coherent condition recalled more of the original Visit Notes content than did
      participants in the Original and the Dictionary conditions combined. However, no
      difference was seen between (Original+Dictionary) and Vocabulary (P=.36) nor
      Coherent and Vocabulary (P=.62). No statistically significant effect of any
      document transformation was found either in the open-ended questionnaire
      (clinical trial: P=.86, Visit Note: P=.20) or in the error rate (clinical trial:
      P=.47, Visit Note: P=.25). However, post hoc power analysis suggested that
      increasing the sample size by approximately 6 participants per condition would
      result in a significant difference for the Visit Note, but not for the clinical
      trial text. CONCLUSIONS: Statistically, the results of this study attest that
      improving coherence has a small effect on consumer comprehension of clinical
      text, but the task is extremely labor intensive and not scalable. Further
      research is needed using texts from more diverse clinical domains and more
      heterogeneous participants, including actual patients. Since comprehensibility of
      clinical text appears difficult to automate, informatics support tools may most
      productively support the health care professionals tasked with making clinical
      information understandable to patients.

PMID- 22138128
TI  - Up-regulation of NDRG2 through nuclear factor-kappa B is required for Leydig cell
      apoptosis in both human and murine infertile testes.
AB  - Many pro-apoptotic factors, such as nuclear factor-kappa B (NF-kappaB) and Fas,
      play crucial roles in the process of Leydig cell apoptosis, ultimately leading to
      male sterility, such as in Sertoli cell only syndrome (SCO) and
      hypospermatogenesis. However, the molecular mechanism of such apoptosis is
      unclear. Recent reports on N-myc downstream-regulated gene 2 (ndrg2) have
      suggested that it is involved in cellular differentiation, development, and
      apoptosis. The unique expression of NDRG2 in SCO and hypospermatogenic testis
      suggests its pivotal role in those diseases. In this study, we analyzed NDRG2
      expression profiles in the testes of normal spermatogenesis patients,
      hypospermatogenesis patients, and SCO patients, as well as in vivo and in vitro
      models, which were Sprague-Dawley rats and the Leydig cell line TM3 treated with
      the Leydig cell-specific toxicant ethane-dimethanesulfonate (EDS). Our data
      confirm that NDRG2 is normally exclusively located in the cytoplasm of Leydig
      cells and is up-regulated and translocates into the nucleus under apoptotic
      stimulations in human and murine testis. Meanwhile, transcription factor NF
      kappaB was activated by EDS administration, bound to the ndrg2 promoter, and
      further increased in expression, effects that were abolished by NF-kappaB
      inhibitor Pyrrolidine dithiocarbamate (PDTC). Furthermore, siRNA knock-down of
      ndrg2 led to increased proliferative or decreased apoptotic TM3 cells, while over
      expression of ndrg2 had the reverse effect. This study reveals that ndrg2 is a
      novel gene that participates in Leydig cell apoptosis, with essential functions
      in testicular cells, and suggests its possible role in apoptotic Leydig cells and
      male fertility.

PMID- 22138130
TI  - Alternative complement pathway of channel catfish (Ictalurus punctatus):
      molecular characterization, mapping and expression analysis of factors Bf/C2 and
      Df.
AB  - The complement system is important in both innate and adaptive host defense
      against microbial infection in vertebrates. It contains three pathways: the
      classical, alternative, and lectin pathways. Complement component factors B and D
      are two crucial proteases in the alternative pathway. In this study, the genes of
      complement factors Bf/C2 and Df from channel catfish, Ictalurus punctatus were
      identified and characterized. Two complement factor B-related genes, Bf/C2A and
      Bf/C2B, and factor D gene Df were identified. Phylogenetic analysis suggested
      that Bf/C2A and Bf/C2B is likely orthologous to factor B and factor C2,
      respectively. Southern blot results suggested that these three genes are all
      single-copy genes in the catfish genome. The catfish Bf/C2A, Bf/C2B and Df genes
      were genetically mapped on linkage group 3, 20 and 29, respectively. Bf/C2A and
      Bf/C2B are highly expressed in liver and kidney, while Df is highly expressed in
      gill and spleen. After infection with Edwardsiella ictaluri, the expression of
      Bf/C2A, Bf/C2B and Df genes were found to be remarkably induced in the gill,
      liver, spleen and kidney at some sampling times, indicating that these three
      complement factors play a pivotal role in immune responses after the bacterial
      infection in catfish.

PMID- 22138131
TI  - SUMOylation in carcinogenesis.
AB  - SUMOylation is a post-translational modification characterized by covalent and
      reversible binding of small ubiquitin-like modifier (SUMO) to a target protein.
      In mammals, four different isoforms, termed SUMO-1, -2, -3 and -4 have been
      identified so far. SUMO proteins are critically involved in the modulation of
      nuclear organization and cell viability. Their expression is significantly
      increased in processes associated with carcinogenesis such as cell growth,
      differentiation, senescence, oxidative stress and apoptosis. Little is known
      about the role of SUMOylation in cancer development. Therefore the present review
      focuses on possible implications of SUMOylation in carcinogenesis highlighting
      its impact as an important regulatory cell cycle protein. Moreover, novel
      opportunities for therapeutic approaches are discussed. The differential
      expression levels, the target protein preferences and the function of the SUMO
      pathway in different cancer subtypes raises unexpected issues questioning our
      understanding of the implication of SUMO in carcinogenesis.

PMID- 22138129
TI  - Antioxidants in Huntington's disease.
AB  - Huntington's disease (HD) is a prototypical neurodegenerative disease in which
      there is selective neuronal degeneration, which leads to progressive disability,
      manifesting itself as a movement disorder, with both psychiatric and cognitive
      impairment. The disease is caused by a cytosine-adenine-guanine (CAG) repeat
      expansion in the huntingtin gene, which causes an expanded polyglutamine repeat
      in the huntingtin protein, resulting in a protein with a novel gain of function.
      The mutant huntingtin protein causes neuronal dysfunction and eventual cell death
      in which transcriptional impairment, excitotoxicity, oxidative damage,
      inflammation, apoptosis and mitochondrial dysfunction are all implicated. A
      critical transcriptional impairment may be impaired expression and function of
      peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha),
      a master co-regulator of mitochondrial biogenesis and expression of antioxidant
      enzymes. A deficiency of PGC-1alpha leads to increased vulnerability to oxidative
      stress and to striatal degeneration. The extent and severity of the oxidative
      damage in HD are features well recognized but perhaps under-appreciated.
      Oxidative damage occurs to lipids, proteins and deoxyribonucleic acid (DNA), and
      it has been suggested that the latter may contribute to CAG repeat expansion
      during DNA repair [1]. A marked elevation of oxidized DNA bases occurs in
      patients' plasma, which may provide a biomarker of disease progression.
      Antioxidants are effective in slowing disease progression in transgenic mouse
      models of HD, and show promise in human clinical trials. Strategies to
      transcriptionally increase expression of antioxidant enzymes by modulating the
      Nrf-2/ARE pathway, or by increasing expression of PGC-1alpha hold great promise
      for developing new treatments to slow or halt the progression of HD. This article
      is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in
      Disease.

PMID- 22138132
TI  - Niacin requirements for genomic stability.
AB  - Through its involvement in over 400 NAD(P)-dependent reactions, niacin status has
      the potential to influence every area of metabolism. Niacin deficiency has been
      linked to genomic instability largely through impaired function of the poly ADP
      ribose polymerase (PARP) family of enzymes. In various models, niacin deficiency
      has been found to cause impaired cell cycle arrest and apoptosis, delayed DNA
      excision repair, accumulation of single and double strand breaks, chromosomal
      breakage, telomere erosion and cancer development. Rat models suggest that most
      aspects of genomic instability are minimized by the recommended levels of niacin
      found in AIN-93 formulations; however, some beneficial responses do occur in the
      range from adequate up to pharmacological niacin intakes. Mouse models show a
      wide range of protection against UV-induced skin cancer well into pharmacological
      levels of niacin intake. It is currently a challenge to compare animal and human
      data to estimate the role of niacin status in the risk of genomic instability in
      human populations. It seems fairly certain that some portion of even affluent
      populations will benefit from niacin supplementation, and some subpopulations are
      likely well below an optimal intake of this vitamin. With exposure to stressors,
      like chemotherapy or excess sunlight, suraphysiological doses of niacin may be
      beneficial.

PMID- 22138133
TI  - Cerebral expression of drug transporters in epilepsy.
AB  - Over-expression of drug efflux transporters at the level of the blood-brain
      barrier (BBB) has been proposed as a mechanism responsible for multidrug
      resistance. Drug transporters in epileptogenic tissue are not only expressed in
      endothelial cells at the BBB, but also in other brain parenchymal cells, such as
      astrocytes, microglia and neurons, suggesting a complex cell type-specific
      regulation under pathological conditions associated with epilepsy. This review
      focuses on the cerebral expression patterns of several classes of well-known
      membrane drug transporters such as P-glycoprotein (Pgp), and multidrug resistance
      associated proteins (MRPs) in the epileptogenic brain. Both experimental and
      clinical evidence of epilepsy-associated cerebral drug transporter regulation and
      the possible mechanisms underlying drug transporter regulation are discussed.
      Knowledge of the cerebral expression patterns of drug transporters in normal and
      epileptogenic brain will provide relevant information to guide strategies
      attempting to overcome drug resistance by targeting specific transporters.

PMID- 22138134
TI  - Enhanced impact of SCN5A mutation associated with long QT syndrome in fetal
      splice isoform.

PMID- 22138135
TI  - Networked multielectrode left ventricular pacing lead for avoidance of phrenic
      nerve stimulation in a canine model.
AB  - BACKGROUND: In cardiac resynchronization therapy, left ventricular stimulation
      may lead to concomitant phrenic nerve stimulation (PNS). OBJECTIVE: To evaluate a
      new networked multielectrode lead with 16 electrode segments (SEGs) configured
      into groups of 4, forming a virtual band (VBAND) around the lead. Each electrode
      is individually programmable using an embedded integrated circuit. METHODS: In 8
      anesthetized dogs, the lead was positioned in a left ventricular coronary vein.
      The voltage thresholds for cardiac stimulation and PNS were measured for
      different electrode configurations, including "VBAND-VBAND" (~conventional
      bipolar pacing), "SEG-VBAND", and "SEG-SEG" (anode and cathode within the same
      VBAND). The measurements were performed (1) with closed chest and (2) after
      opening the chest and repositioning the phrenic nerve to above the lead,
      simulating a worst-case scenario. RESULTS: Compared with the conventional VBAND
      VBAND stimulation, the SEG-SEG stimulation increased the PNS threshold and raised
      the difference between phrenic and cardiac thresholds from 6.2 +/- 2.3 to 9.5 +/
      0.3 V in the closed chest condition and from 1.4 +/- 1.6 to 9.0 +/- 1.0 V in the
      worst-case scenario (both P < .001). Both SEG-VBAND and SEG-SEG stimulations
      reduced the cardiac threshold and increased pacing impedance, thus reducing the
      required cardiac pacing power by 77%-80% (P <.001 and P <.01 for closed and open
      chest, respectively). CONCLUSION: This novel multielectrode pacing lead achieves
      low cardiac and high extracardiac stimulation thresholds during left ventricular
      pacing in a canine model. The virtual elimination of PNS may facilitate and
      improve the application of cardiac resynchronization therapy.

PMID- 22138136
TI  - Renin-angiotensin blockade as primary prevention during right ventricular pacing:
      an alternative strategy in managing cardiac dyssynchrony.

PMID- 22138137
TI  - Functional activation of glutamate ionotropic receptors in the human peripheral
      retina.
AB  - Glutamate is the major neurotransmitter in the vertebrate retina. Neurons
      involved in the glutamate pathway express alpha-amino-3-hydroxyl-5
      methylisoxazole-4-propionic acid (AMPA), kainic acid (KA) and N-methyl-D
      aspartate (NMDA) receptors. Functional characterization of these ionotropic
      glutamate receptors can be achieved by using a cation channel permeating probe
      named agmatine (1-amino-4-guanidobutane; AGB). Retinal mapping using this
      guanidinium analog has certain advantages including the immunocytochemical
      identification of a whole population of neurons expressing functional glutamate
      gated receptor channels. We have extended AGB studies into the functionality of
      ionotropic receptors in peripheral aged human retina to serve as a comparison for
      functional analysis of retinopathies such as retinal detachment. We probed the
      human retina with AGB after activation with AMPA, KA and NMDA. The results showed
      patterns of AGB entry into neurons consistent with those previously observed in
      subunit localization studies in adult mammalian retinae including primates.
      Application of 30 MUM AMPA activated receptors in virtually all calretinin
      immunoreactive AII amacrine cells in the mid-peripheral human retina. About half
      of the AII amacrine cells showed AGB permeation after incubation with 50 MUM KA.
      Some bipolar cells including DB3 OFF bipolar cells displayed functional KA
      receptors. Colocalization of AGB with parvalbumin labeled horizontal cells
      revealed functional KA and AMPA receptors with no responsiveness to NMDA
      activation. NMDA activation resulted in AGB labeling of ganglion cells and
      amacrine cells. The present study provides a description of functional ionotropic
      glutamate receptors in the aged mid-peripheral human retina.

PMID- 22138138
TI  - The laborist model of obstetric care: we need more evidence.
AB  - Literature suggesting improved patient outcomes and patient satisfaction with the
      hospitalist model of inpatient medical care coupled with the desire to improve
      provider satisfaction led to the introduction of the laborist in obstetrics. This
      represents a significant change in the way obstetrics has been experienced and
      practiced from both a patient and provider perspective. The laborist was designed
      as a plausible model of obstetric care delivery where hospitals employ physicians
      to provide continuous coverage of labor and delivery units without other
      competing clinical duties. Anecdotal use of the laborist model in the provision
      of obstetric care is growing rapidly, despite the lack of research regarding its
      impact on maternal outcomes, neonatal outcomes, patient and provider
      satisfaction, and graduate medical education. We provide an overview of both the
      positive and negative attributes of this model of obstetric care delivery,
      discuss the current state of research addressing these attributes, and propose a
      research strategy to improve understanding of the impact of this model of care
      delivery.

PMID- 22138139
TI  - Mechanical aspects of CO2 angiography.
AB  - The aim of this paper is to clarify some physical-mechanical aspects involved in
      the carbon dioxide angiography procedure (CO2 angiography), with a particular
      attention to a possible damage of the vascular wall. CO2 angiography is widely
      used on patients with iodine intolerance. The injection of a gaseous element, in
      most cases manually performed, requires a long training period. Automatic systems
      allow better control of the injection and the study of the mechanical behaviour
      of the gas. CO2 injections have been studied by using manual and automatic
      systems. Pressures, flows and jet shapes have been monitored by using a
      cardiovascular mock. Photographic images of liquid and gaseous jet have been
      recorded in different conditions, and the vascular pressure rises during
      injection have been monitored. The shape of the liquid jet during the catheter
      washing phase is straight in the catheter direction and there is no jet during
      gas injection. Gas bubbles are suddenly formed at the catheter's hole and move
      upwards: buoyancy is the only governing phenomenon and no bubbles fragmentation
      is detected. The pressure rise in the vessel depends on the injection pressure
      and volume and in some cases of manual injection it may double the basal vascular
      pressure values. CO2 angiography is a powerful and safe procedure which diffusion
      will certainly increase, although some aspects related to gas injection and
      chamber filling are not jet well known. The use of an automatic system permits
      better results, shorter training period and limitation of vascular wall damage
      risk.

PMID- 22138140
TI  - Prognostic value of copeptin: one-year outcome in patients with traumatic brain
      injury.
AB  - High plasma copeptin level has been associated with one-month mortality after
      traumatic brain injury. However, not much is known regarding its relation with
      long-term outcome. Thus, we investigated the ability of copeptin to predict 1
      year outcome in patients with traumatic brain injury. One hundred and six healthy
      controls and 106 patients with acute severe traumatic brain injury were included.
      Plasma samples were obtained on admission. Its concentration was measured by
      enzyme-linked immunosorbent assay. Forty-eight patients (45.3%) suffered from
      unfavorable outcome (Glasgow Outcome Scale score of 1-3) and 31 patients (29.2%)
      died in 1 year after traumatic brain injury. Upon admission, plasma copeptin
      level in patients was substantially higher than that in healthy controls. A
      forward stepwise logistic regression selected plasma copeptin level as an
      independent predictor for 1-year unfavorable outcome and mortality of patients. A
      receiver operating characteristic curve analysis showed plasma copeptin level
      predicted 1-year unfavorable outcome and mortality obviously. The predictive
      value of the copeptin concentration was thus similar to that of Glasgow Coma
      Scale score for the prediction of unfavorable outcome and mortality after 1 year.
      In a combined logistic-regression model, copeptin improved the area under curve
      of Glasgow Coma Scale score for the prediction of unfavorable outcome and
      mortality after 1 year, but the differences were not significant. Thus, copeptin
      level is a useful, complementary tool to predict functional outcome and mortality
      1 year after traumatic brain injury.

PMID- 22138141
TI  - Biochemical characterization of atherosclerotic plaques by endogenous
      multispectral fluorescence lifetime imaging microscopy.
AB  - OBJECTIVE: To investigate the potential of endogenous multispectral fluorescence
      lifetime imaging microscopy (FLIM) for biochemical characterization of human
      coronary atherosclerotic plaques. METHODS: Endogenous multispectral FLIM imaging
      was performed on the lumen of 58 segments of postmortem human coronary artery.
      The fluorescence was separated into three emission bands targeting the three main
      arterial endogenous fluorophores (390+/-20 nm for collagen, 452+/-22.5 nm for
      elastin, and 550+/-20 for lipids). The fluorescence normalized intensity and
      average lifetime from each emission band was used to classify each pixel of an
      image as either "High-Collagen", "High-Lipids" or "Low-Collagen/Lipids" via
      multiclass Fisher's linear discriminant analysis. RESULTS: Classification of
      plaques as either "High-Collagen", "High-Lipids" or "Low-Collagen/Lipids" based
      on the endogenous multispectral FLIM was achieved with a sensitivity/specificity
      of 96/98%, 89/99%, and 99/99%, respectively, where histopathology served as the
      gold standard. CONCLUSION: The endogenous multispectral FLIM approach we have
      taken, which can readily be adapted for in vivo intravascular catheter based
      imaging, is capable of reliably identifying plaques with high content of either
      collagen or lipids.

PMID- 22138142
TI  - Low ankle-brachial index predicts early risk of recurrent stroke in patients with
      acute cerebral ischemia.
AB  - OBJECTIVE: Low ankle-brachial blood pressure index (ABI) identifies patients with
      symptomatic and asymptomatic peripheral arterial disease (PAD). We sought to
      investigate the association of low ABI with early risk of stroke recurrence in
      patients with acute cerebral ischemia (ACI) and without history of symptomatic
      PAD. METHODS: Consecutive patients with acute ischemic stroke (AIS) or transient
      ischemic attack (TIA) and no previous history of PAD were prospectively evaluated
      with ABI measurements. Demographic characteristics, vascular risk factors and
      secondary prevention therapies were documented. An ABI <=0.90 in either leg was
      considered as evidence of asymptomatic PAD, and an ABI >0.90 was considered as
      normal. Patients with elevated ABI (>1.30) were excluded. The outcome of interest
      was recurrent stroke during 30-day follow-up. RESULTS: A total of 176 patients
      with acute cerebral ischemia (mean age 64+/-14 years, 59.1% men, 76.7% AIS) were
      evaluated. Asymptomatic PAD was detected in 14.8% (95%CI: 10.2-20.8%) of the
      studied population. The following factors were independently associated with low
      ABI on multivariate logistic regression models, after adjustment for potential
      confounders: coronary artery disease (p=0.008), diabetes mellitus (p=0.017) and
      increasing age (p=0.042). The cumulative 30-day recurrence rate was higher in
      patients with low ABI (19.2%; 95%CI: 4.1-34.3) compared to the rest (3.3%; 95%CI:
      0.4-6.2%; p=0.001). Atherothrombotic stroke (ASCO grade I; p<0.001), increasing
      age (p=0.002) and low ABI (p=0.004) were independent predictors of stroke
      recurrence on multivariate Cox regression models adjusting for confounders.
      CONCLUSIONS: Low ABI appears to be associated with a higher risk of early
      recurrent stroke in patients with ACI and no history of symptomatic PAD.

PMID- 22138143
TI  - Adiponectin G276T gene polymorphism is associated with cardiovascular disease in
      Japanese patients with type 2 diabetes.
AB  - OBJECTIVE: Adiponectin has anti-atherogenic properties and reduced serum
      adiponectin levels are associated with cardiovascular disease (CVD). In this
      study, we examined the relationship between CVD and adiponectin (ADIPOQ) gene
      G276T polymorphism that is associated with serum adiponectin level in a large
      cohort of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We enrolled 2637
      Japanese type 2 diabetic subjects (males, 61.1%; age, 54.9+/-7.9 years old),
      determined their genotypes regarding ADIPOQ G276T polymorphisms, and evaluated
      the association between this polymorphism and the prevalence of CVD (myocardial
      infarction and/or cerebral infarction). RESULTS: The prevalence of CVD tended to
      be higher as the number of G alleles increased [GG (9.5%), GT (6.8%), TT (5.6%),
      p value for trend=0.0059] and was significantly higher in the subjects with GG
      genotype compared to those with GT or TT genotype (9.5% vs. 6.6%, p=0.0060).
      Multiple logistic regression analyses revealed that the number of G alleles (Odds
      ratio (OR)=1.49 with 95%CI 1.09-2.05, p=0.0125) and GG genotype (OR=1.66 with
      95%CI 1.13-2.43, p=0.0098) were significantly associated with CVD even after
      adjustment for conventional risk factors. Interestingly, the presence of obesity
      further and significantly increased the risk of CVD in the subjects with GG
      genotype (OR=1.67 with 95%CI 1.14-2.44, p=0.0090) but not in the subjects with TT
      or GT genotype (OR=1.17 with 95%CI 0.73-1.89, NS). CONCLUSIONS: It is likely that
      the G allele of the ADIPOQ G276T polymorphism is a susceptibility allele for CVD
      in Japanese type 2 diabetic patients, especially when they accompany obesity.

PMID- 22138144
TI  - Dietary fat, abdominal obesity and smoking modulate the relationship between
      plasma complement component 3 concentrations and metabolic syndrome risk.
AB  - OBJECTIVE: Chronic inflammation plays a role in the pathogenesis of metabolic
      syndrome (MetS) and cardiovascular disease (CVD). Complement component 3 (C3) is
      a novel cardiometabolic risk factor. Whether dietary fat intake modulates MetS
      risk conferred by elevated C3 concentrations is unknown. Our objective is to
      investigate the relationship between C3 concentrations and risk of the MetS and
      its phenotypes, and to further examine whether dietary fat intake modulates these
      relationships. METHODS: Biochemical, dietary and lifestyle measurements were
      determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls
      (n=1754). RESULTS: Elevated C3 concentrations (>median) were associated with
      increased risk of impaired insulin sensitivity [OR 1.78, CI 1.34-2.36, P<0.0001],
      insulin resistance [OR 1.73, CI 1.31-2.89, P=0.0001], abdominal obesity [OR 2.15,
      CI 1.43-3.24, P=0.0002] and low HDL cholesterol [OR 1.40, CI 1.05-1.86, P=0.02]
      compared to low C3 concentrations. Increased MetS risk conferred by elevated C3
      concentrations [OR 3.11, 95% CI 2.52-3.82, P<0.0001] was further accentuated
      among high dietary fat consumers [OR 4.80, 95% CI 2.77-8.33, P<0.0001]
      (particularly of saturated [OR 4.05, 95% CI 2.33-7.05, P<0.0001] and
      monounsaturated fat [OR 4.48, 95% CI 2.62-7.56, P<0.0001]), and smokers [OR 3.83,
      95% CI 2.12-6.94, P<0.0001], however this effect was abolished in abdominally
      lean individuals [OR 1.46, 95% CI 0.69-3.14, P=0.33]. CONCLUSIONS: Dietary fat
      (intake and composition), abdominal obesity and smoking modulate the relationship
      between elevated plasma C3 concentrations and MetS risk.

PMID- 22138145
TI  - Learned host preference in a Chagas disease vector, Rhodnius prolixus.
AB  - It has been largely assumed that the individual experience of disease vector
      insects may affect host choice and, as a consequence, have an important influence
      on parasite transmission. In particular, it is speculated that vector insects
      should be able to learn and remember the most and/or less defensive hosts,
      shifting their preference accordingly. Nevertheless, despite the invested efforts
      in testing the capacity to learn and remember information of blood-sucking
      insects, only little conclusive information has been obtained hitherto. Recently,
      the ability of Rhodnius prolixus to associate a behaviourally neutral odour to
      the perspective of either obtaining a blood-meal or being punished has been
      demonstrated, the same odour becoming attractant or repellent for the bugs,
      respectively, according to the individual previous experience. The present work
      represents a step forward in the study of the cognitive abilities of Chagas
      disease vectors and their influence on host choice. We tested whether or not bugs
      bias their choice for a host based on the association of its odour with a
      negative experience. Our results show that whereas naive bugs presented no
      preference when confronted to the odour of two different hosts, bugs previously
      exposed to the contingency of the odour of one host and a mechanical perturbation
      mimicking defensive behaviour, biased their preference towards the other host.
      This constitutes the first evidence of olfactory conditioning to host odours in
      triatomine bugs, vectors of Chagas disease and one of the few available up to
      date on haematophagous insects. The epidemiological significance of this finding
      is discussed.

PMID- 22138146
TI  - Characterization of type "B" esterases and hepatic CYP450 isoenzimes in
      Senegalese sole for their further application in monitoring studies.
AB  - In fish, the role that cholinesterases (ChEs) play in tissues other than those
      implicated in neural activity, as well as the involvement of carboxylesterases
      (CbEs) and cytochrome P450 isoenzymes (CYPs) in drug metabolism needs
      investigation. For that, Senegalese sole (Solea senegalensis) specimens were
      selected for characterization of several type B esterases and hepatic CYPs in
      order to further use this fish as sentinel. ChEs (acetylcholinesterase (AChE) and
      pseudocholinesterases (butyrylcholinesterase-BuChE and propionilcholinesterase
      PrChE)) and CbEs were measured in brain, plasma, kidney, liver, gonad, muscle and
      gills. Moreover, seven fluorimetric substrates were selected to study CYP related
      activities in fish liver. The results showed that AChE was the dominant ChE form
      in brain whereas pseudocholinesterases were absent in most tissues, as
      demonstrated by low enzymatic activities using specific substrates and the lack
      of inhibition by iso-OMPA. Plasma exhibited trace activities of all the esterases
      assayed and no BuChE activity. CbEs were dominant in liver, but they were also
      present in kidney and brain. For CbE determination, alpha-naphtyl acetate
      (alphaNA) was seen as the most adequate substrate as it displayed higher
      enzymatic activities and showed more in vitro sensitivity to the carbamate
      eserine and the organophosphate pesticide dichlorvos. Alkoxyresorufin-O
      dealkylase (EROD and BFCOD) activities, indicative in mammals of CYP1A and CYP3A
      subfamilies, respectively, were the highest microsomal CYP-related activities in
      liver. The results of this preliminary work allow us to select the most adequate
      esterase substrate, tissue and hepatic CYP substrate for further monitoring
      studies.

PMID- 22138147
TI  - Effects of Pb on the oxidative stress and antioxidant response in a Pb
      bioaccumulator plant Vallisneria natans.
AB  - The effects of Pb on photosynthetic pigments, oxidative stress and antioxidant
      response were assayed using biochemical and histochemical methods in leaves of
      Vallisneria natans (Lour.) Hara treated with 0-100 MUM Pb(2+) for 0-6d. The Pb
      content increased with the increase of exposure duration and a highest Pb uptake
      value (about 9.4 mg Pbg(-1) dry weight) was obtained at 6d. Pb induced the
      accumulation of H(2)O(2) and O(2)(-). The increase of malondialdehyde content and
      the decrease of total chlorophyll and carotenoids were detected in V. natans
      under Pb stress. Activities of NAD(P)H oxidase, guaiacol peroxidase, glutathione
      reductase and ascorbate peroxidase increased at 75 MUM Pb(2+) for 2-6 days, while
      activities of superoxide dismutase and catalase and the content of ascorbic acid
      increased within two days in plants exposed to 75 MUM Pb(2+) and decreased
      thereafter. The Pb uptake and accumulation mechanism were discussed.

PMID- 22138148
TI  - Inhibitory effects of silver nanoparticles in two green algae, Chlorella vulgaris
      and Dunaliella tertiolecta.
AB  - Freshwater microalga Chlorella vulgaris and marine microalga Dunaliella
      tertiolecta were used to investigate toxic effects induced by 50 nm silver
      nanoparticles (AgNPs). To induce AgNPs effect, we exposed Chlorella vulgaris and
      Dunaliella tertiolecta for 24h to 0-10 mg/L. We showed that growth media had
      different effects in AgNPs agglomerates' formation. Cellular viability, reactive
      oxygen species (ROS) formation and lipids peroxidation were employed to assess
      the toxic effects of AgNPs. AgNPs were able to interact directly with the
      Chlorella vulgaris cells surface and large aggregates were observed. AgNPs have a
      negative effect on Chlorella vulgaris and Dunaliella tertiolecta, as manifested
      by a strong decrease in chlorophyll content, viable algal cells, increased ROS
      formation and lipids peroxidation. The variability in sensitivity of both algae
      towards AgNPs was observed. We conclude that AgNPs have a negative effect on
      aquatic algae and these alterations might have serious consequences on structure
      and function of aquatic plant communities.

PMID- 22138149
TI  - Effects of Na2CO3 stress on photosynthesis and antioxidative enzymes in endophyte
      infected and non-infected rice.
AB  - Endophyte infected and uninfected seedlings of rice (Oryza sativa L.) were
      subjected to five different levels of Na(2)CO(3) for 2 weeks. Under both
      Na(2)CO(3) stress as well as no stress, endophyte-infected plants were higher for
      above-ground dry weight and shoot length, but lower for root length compared to
      non-infected controls, and there was no significant difference for below-ground
      dry weight. Chlorophylls and carotenoid contents, net photosynetic rate,
      transpiration rate, catalase and peroxidase activities increased, but
      malondialdehyde content declined in the infected plants compared to non-infected
      controls under Na(2)CO(3) stress. Compared to non-infected controls, water use
      efficiency, stomatal conductance, chlorophyll fluorescence parameters (F(v)/F(m),
      F(v)/F(o)) and superoxide dismutase activity in infected plants increased under
      high concentrations of Na(2)CO(3) while there was no significant difference under
      low concentrations of Na(2)CO(3). Endophyte infection was concluded to be
      beneficial to the growth and antioxidative mechanisms in Oryza sativa under
      Na(2)CO(3) stress.

PMID- 22138150
TI  - The expression of Visinin-like 1 during mouse embryonic development.
AB  - Visinin like 1 (Vsnl1) encodes a calcium binding protein which is well conserved
      between species. It was originally found in the brain and its biological
      functions in central nervous system have been addressed in several studies. Low
      expression levels have also been found in some peripheral organs, but very little
      information is available regarding its physiological roles in non-neuronal
      tissues. Except for the kidney, the expression pattern of Vsnl1 mRNA and protein
      has not yet been addressed during embryogenesis. By in situ hybridization and
      immunolabeling we have extensively analyzed the expression pattern of Vsnl1
      during murine development. Vsnl1 specifies the cardiac primordia and its
      expression becomes restricted to the atrial myocardium after heart looping.
      However, in the adult heart, Vsnl1 is expressed by all four cardiac chambers. It
      also serves as a specific marker for the cardiomyocyte-derived structures in the
      systemic and pulmonary circulation. Vsnl1 is dynamically expressed also by many
      other organs during development e.g. taste buds, cochlea, thyroid, tooth,
      salivary and adrenal gland. The stage specific expression pattern of Vsnl1 makes
      it a potentially useful marker particularly in studies of cardiac and vascular
      morphogenesis.

PMID- 22138151
TI  - Reduced mRNA secondary-structure stability near the start codon indicates
      functional genes in prokaryotes.
AB  - Several recent studies have found that selection acts on synonymous mutations at
      the beginning of genes to reduce mRNA secondary-structure stability, presumably
      to aid in translation initiation. This observation suggests that a metric of
      relative mRNA secondary-structure stability, Z(DeltaG), could be used to test
      whether putative genes are likely to be functionally important. Using the
      Escherichia coli genome, we compared the mean Z(DeltaG) of genes with known
      functions, genes with known orthologs, genes where function and orthology are
      unknown, and pseudogenes. Genes in the first two categories demonstrated similar
      levels of selection for reduced stability (increased Z(DeltaG)), whereas for
      pseudogenes stability did not differ from our null expectation. Surprisingly,
      genes where function and orthology were unknown were also not different from the
      null expectation, suggesting that many of these open reading frames are not
      functionally important. We extended our analysis by constructing a Bayesian
      phylogenetic mixed model based on data from 145 prokaryotic genomes. As in E.
      coli, genes with no known function had consistently lower Z(DeltaG), even though
      we expect that many of the currently unannotated genes will ultimately have their
      functional utility discovered. Our findings suggest that functional genes tend to
      evolve increased Z(DeltaG), whereas nonfunctional ones do not. Therefore,
      Z(DeltaG) may be a useful metric for identifying genes of potentially important
      function and could be used to target genes for further functional study.

PMID- 22138153
TI  - Free chelatable zinc modulates the cholinergic function during hypobaric hypoxia
      induced neuronal damage: an in vivo study.
AB  - The deregulation of cholinergic system and associated neuronal damage is thought
      to be a major contributor to the pathophysiologic sequelae of hypobaric hypoxia
      induced memory impairment. Uniquely, the muscarinic receptors also play a role in
      zinc uptake. Despite the potential role of muscarinic receptors in the
      development of post hypoxia cognitive deficits, no studies to date have evaluated
      the mechanistic relationship between memory dysfunction and zinc homeostasis in
      brain. In the present study, we evaluated the effect of Ca(2)EDTA, a specific
      zinc chelator in the spatial working and associative memory deficits following
      hypobaric hypoxia. Our results demonstrate that accumulation of intracellular
      free chelatable zinc in the hippocampal CA3 pyramidal neurons is accompanied with
      neuronal loss and memory impairment in hypobaric hypoxic condition. Chelation of
      this free zinc with Ca(2)EDTA (1.25 mM/kg) ameliorated the hippocampus-dependent
      spatial as well as associative memory dysfunction and neuronal damage observed on
      exposure to hypobaric hypoxia. The zinc chelator significantly alleviated the
      downregulation in expression of choline acetyltransferase, muscarinic receptor 1
      and 4, and acetylcholinesterase activity due to hypobaric hypoxia. Our data
      suggest that the free chelatable zinc released during hypobaric hypoxia might
      play a critical role in the neuronal damage and the alteration in cholinergic
      function associated with hypobaric hypoxia-induced memory impairment. We
      speculate that zinc chelation might be a potential therapy for hypobaric hypoxia
      induced cognitive impairment.

PMID- 22138154
TI  - Cholinergic suppression of excitatory synaptic transmission in layers II/III of
      the parasubiculum.
AB  - Layer II of the parasubiculum (PaS) receives excitatory synaptic input from the
      CA1 region of the hippocampus and sends a major output to layer II of the medial
      and lateral entorhinal cortex. The PaS also receives heavy cholinergic
      innervation from the medial septum, which contributes to the generation of theta
      frequency (4-12 Hz) electroencephalographic (EEG) activity. Cholinergic receptor
      activation exerts a wide range of effects in other areas of the hippocampal
      formation, including membrane depolarization, changes in neuronal excitability,
      and suppression of excitatory synaptic responses. The present study was aimed at
      determining how cholinergic receptor activation modulates excitatory synaptic
      input to the layer II/III neurons of the PaS in acute brain slices. Field
      excitatory postsynaptic potentials (fEPSPs) in layer II/III of the PaS were
      evoked by stimulation of either layer I afferents, or ascending inputs from layer
      V. Bath-application of the cholinergic agonist carbachol (0.5-10 MUM) suppressed
      the amplitude of fEPSPs evoked by both superficial- and deep layer stimulation,
      and also enhanced paired-pulse facilitation. Constant bath-application of the
      GABA(A) antagonist bicuculline (10 MUM) failed to eliminate the suppression,
      indicating that the cholinergic suppression of fEPSPs is not due to increased
      inhibitory tone. The muscarinic receptor antagonist atropine (1 MUM) blocked the
      suppression of fEPSPs, and the selective M(1)-preferring receptor antagonist
      pirenzepine (1 MUM), but not the M(2)-preferring antagonist methoctramine (1-5
      MUM), also significantly attenuated the suppression. Therefore, cholinergic
      receptor activation suppresses excitatory synaptic input to layer II/III neurons
      of the PaS, and this suppression is mediated in part by M(1) receptor activation.

PMID- 22138152
TI  - Maize rough endosperm3 encodes an RNA splicing factor required for endosperm cell
      differentiation and has a nonautonomous effect on embryo development.
AB  - Endosperm and embryo development are coordinated via epigenetic regulation and
      signaling between these tissues. In maize (Zea mays), the endosperm-embryo
      signals are not known, but endosperm cellularization is a key event for embryos
      to form shoots and roots. We screened seed mutants for nonautonomous functions in
      endosperm and embryo development with genetically nonconcordant seeds and
      identified the recessive mutant rough endosperm3 (rgh3). The wild-type Rgh3
      allele is required in the endosperm for embryos to develop and has an autonomous
      role in embryo and seedling development. Endosperm cell differentiation is
      defective in rgh3. Results from endosperm cell culture indicate that rgh3 mutants
      remain in a proliferative state through mid-seed development. Rgh3 encodes the
      maize U2AF(35) Related Protein (URP), an RNA splicing factor involved in both U2
      and U12 splicing. The Rgh3 allele produces at least 19 alternative splice
      variants with only one isoform encoding a full-length ortholog to URP. The full
      length RGH3alpha isoform localizes to the nucleolus and displays a speckled
      pattern within the nucleoplasm, and RGH3alpha colocalizes with U2AF(65). A survey
      of alternatively spliced transcripts found that, in the rgh3 mutant, a fraction
      of noncanonical splicing events are altered. Our findings suggest that
      differentiation of maize endosperm cell types is necessary for embryos to
      develop. The molecular cloning of Rgh3 suggests that alternative RNA splicing is
      needed for cell differentiation, development, and plant viability.

PMID- 22138155
TI  - FLZ protects dopaminergic neuron through activating protein kinase B/mammalian
      target of rapamycin pathway and inhibiting RTP801 expression in Parkinson's
      disease models.
AB  - The pathogenesis of Parkinson's disease is characterized by progressive
      degeneration of dopaminergic neurons in substantia nigra (SNpc). FLZ, a novel
      synthetic squamosamide derivative from a Chinese herb, has been shown to have
      neuroprotective effects in experimental Parkinson's disease (PD) models. However,
      it is still unclear whether FLZ protects against PD through regulating the
      function of dopaminergic system. In this study, we carried out a set of in vitro
      and in vivo experiments to address these questions. Oral administration of FLZ
      significantly improved motor dysfunction of mice challenged by MPTP. The
      beneficial effects of FLZ on motor behavior attributed to the elevation of
      dopamine level in striatum, tyrosine hydroxylase (TH)-positive cells, and TH
      activity in the middle brain of mouse. Mechanism study showed that treatment of
      FLZ increased the phosphorylation of activating protein kinase B (Akt) and
      mammalian target of rapamycin (mTOR). Using LY294002 to block phosphoinositide 3
      kinases (PI3K)/Akt signaling pathway prevented the phosphorylation of mTOR and
      attenuated the neuroprotection of FLZ in MN9D cells challenged by MPP(+). In
      addition, FLZ reduced the expression of RTP801, an important protein in PD, in
      mice and cells intoxicated by MPTP/MPP(+). Taken together, these results revealed
      a novel role that FLZ elevated TH expression and activity in dopaminergic neuron
      through activation of Akt/mTOR survival pathway and inhibition of RTP801 in
      MPTP/MPP(+)-induced PD models. The data also provided evidence that FLZ had
      potent neuroprotecive effects and might become a new promising anti-PD drug.

PMID- 22138157
TI  - Memory for emotional simulations: remembering a rosy future.
AB  - Mental simulations of future experiences are often concerned with emotionally
      arousing events. Although it is widely believed that mental simulations enhance
      future behavior, virtually nothing is known about how memory for these
      simulations changes over time or whether simulations of emotional experiences are
      especially well remembered. We used a novel paradigm that combined recently
      developed methods for generating simulations of future events and well
      established procedures for testing memory to examine the retention of positive,
      negative, and neutral simulations over delays of 10 min and 1 day. We found that
      at the longer delay, details associated with negative simulations were more
      difficult to remember than details associated with positive or neutral
      simulations. We suggest that these effects reflect the influence of the fading
      affect bias, whereby negative reactions fade more quickly than positive
      reactions, and that this influence results in a tendency to remember a rosy
      simulated future. We discuss implications of our findings for individuals with
      affective disorders, such as depression and anxiety.

PMID- 22138156
TI  - Cannabinoid receptor type 1 antagonism significantly modulates basal and loud
      noise induced neural and hypothalamic-pituitary-adrenal axis responses in male
      Sprague-Dawley rats.
AB  - Altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated
      with stress-induced changes in cognitive, emotional, and physical health. Recent
      evidence indicates that the endogenous cannabinoid (eCB) system may modulate HPA
      axis function both directly and more centrally, via regulation of limbic brain
      systems that control HPA-axis activity. The current study examines the
      contribution of cannabinoid type 1 (CB1) receptor modulation throughout the
      neuraxis on control and stress-induced HPA-axis activity. Adult male Sprague
      Dawley rats were given intraperitoneal injections of either CB1 receptor
      antagonist (AM251, 2 mg/kg) or vehicle 30 min prior to a session of loud white
      noise stress (95 dBA for 30 min) or placement in a familiar sound-proof chamber.
      Immediately following stress and control treatments, rats were killed, the brains
      and pituitary glands were excised for subsequent immediate early gene (c-fos
      mRNA) measurement, and trunk blood was collected for subsequent determination of
      corticosterone (CORT) and adrenocorticotropic (ACTH) hormone levels. AM251
      treatment resulted in a potentiated plasma ACTH response to loud noise stress.
      AM251 treatment also increased stress-induced plasma CORT levels, but that
      increase may be due to an increase in basal plasma CORT levels, as was evident in
      control rats. AM251 treatment produced three distinctive c-fos mRNA response
      patterns across the various brain regions examined. In cortical (prelimbic,
      infralimbic, somatosensory, and auditory) and some subcortical structures
      (basolateral amygdala and paraventricular nucleus of the hypothalamus), AM251
      treatment produced a substantial increase in c-fos mRNA that was comparable with
      the elevated c-fos mRNA levels present in those brain regions of both vehicle and
      AM251-treated stressed rats. In some other subcortical structures (bed nucleus of
      the stria terminalis and medial preoptic area) and the anterior pituitary, AM251
      treatment produced a c-fos mRNA response pattern that was similar to the response
      pattern of ACTH hormone levels, that is, no effect on no noise control levels,
      but an augmentation of stress-induced levels. Conversely, in the medial
      geniculate and ventral posterior thalamus, AM251 treatment inhibited stress
      induced c-fos mRNA induction. These data indicate that disruption of eCB
      signaling through CB1 receptors results in potentiated neural and endocrine
      responses to loud noise stress, but also substantial increases in activity in
      various brain regions and the adrenal gland.

PMID- 22138158
TI  - Does the level at which cognitive change occurs change with age?
AB  - Increased age in adulthood is associated with systematically more negative
      cognitive change, but relatively little is known about the nature of change at
      different ages. The present study capitalized on the hierarchical structure of
      cognitive abilities to investigate possible age differences in the level at which
      change operates. Reductions in the longitudinal associations between test scores
      when across-time relations were specified at different levels in the hierarchical
      structure were used to infer contributions to change from the level of abilities
      and from the level of a general factor. Although the pattern of influences varied
      across different cognitive abilities, the results revealed little or no age
      differences in the relative contributions to change from different levels in the
      hierarchy.

PMID- 22138159
TI  - The timing and the mode of evolution of wild grapes (Vitis).
AB  - Wild grapes are woody climbers, found mostly in temperate regions of the northern
      hemisphere, comprising the genus Vitis. Despite its importance, the evolutionary
      history of Vitis is still contentious. Past studies have led to conflicting
      hypotheses about the phylogeny, speciation events, and biogeographic history of
      the genus. Here we investigate the evolutionary history of Vitis using data from
      four chloroplast spacers (trnH-psbA, trnK-rps16, trnF-nahJ, and rpl32-trnL) and
      the nuclear gene RPB2-I, and we explore mechanisms that could have shaped the
      observed distribution of current species. Maximum likelihood and Bayesian
      analyses provided similar results, strongly supporting the presence of two
      subgenera and suggesting a species clustering within subgenus Vitis that mainly
      mirrors the disjunction between the Old and New World. Vitis vinifera subsp.
      sylvestris was found to be sister to the Asian species while three major clades
      were found in the American species. A network approach confirmed the main
      geographic groups and highlighted different chloroplast haplotype patterns
      between Asian and American species. Molecular dating analysis provided the time
      boundaries to discuss our results. Our study shows wild grape diversification to
      be a continuous and complex process that concerned the Tertiary as well as the
      Quaternary, most likely involving both geographical and climatic forces. Local
      variations in extent and timing of these forces were discussed based on observed
      differences between groups. In the context of the Tertiary-Quaternary debate, we
      provide evidence in favor of the "continuous hypothesis" to explain present
      diversity. Finally, two directions for future research are highlighted: (i) was
      the earliest grape American or Asian? and (ii) are all modern grape species real?

PMID- 22138160
TI  - Phylogeographic patterns of decapod crustaceans at the Atlantic-Mediterranean
      transition.
AB  - Comparative multispecies studies allow contrasting the effect of past and present
      oceanographic processes on phylogeographic patterns. In the present study, a
      fragment of the COI gene was analyzed in seven decapod crustacean species from
      five families and with different bathymetric distributions. A total of 769
      individuals were sampled along the Atlantic-Mediterranean transition area in
      order to test the effect of three putative barriers to gene flow: Strait of
      Gibraltar, Almeria-Oran Front and Ibiza Channel. A significant effect of the
      Strait of Gibraltar was found in the crabs Liocarcinus depurator and Macropipus
      tuberculatus. The Ibiza Channel had a significant effect for L. depurator.
      However, the Almeria-Oran front was not found to have a significant effect on any
      of the studied species. Higher levels of population structure were found in
      shallow-water species, although the number of species sampled should be increased
      to obtain a conclusive pattern. The haplotypes within the different species
      coalesced at times that could be related with past climatic events occurring
      before, during and after the last glacial maximum. Given the large diversity of
      phylogeographic patterns obtained within decapods, it is concluded that both
      historical and contemporary processes (marine current patterns, bathymetry and
      life-history traits) shape the phylogeographic patterns of these crustaceans.

PMID- 22138163
TI  - Cannabinoid CB1 receptor restrains accentuated activity of hypothalamic
      corticotropin-releasing factor and brainstem tyrosine hydroxylase neurons in
      endotoxemia-induced hypophagia in rats.
AB  - It is well known that endocannabinoids play an important role in the regulation
      of food intake and body weight. Endocannabinoids and cannabinoid receptors are
      found in the hypothalamus and brainstem, which are central areas involved in the
      control of food intake and energy expenditure. Activation of these areas is
      related to hypophagia observed during inflammatory stimulus. This study
      investigated the effects of cannabinoid (CB1) receptor blockade on
      lipopolysaccharide (LPS)-induced hypophagia. Male Wistar rats were pretreated
      with rimonabant (10 mg/kg, by gavage) or vehicle; 30 min later they received an
      injection of either LPS (100 MUg/kg, intraperitoneal) or saline. Food intake,
      body weight, corticosterone response, CRF and CART mRNA expression, Fos-CRF and
      Fos-alpha-MSH immunoreactivity in the hypothalamus and Fos-tyrosine hydroxylase
      (TH) immunoreactivity in the brainstem were evaluated. LPS administration
      decreased food intake and body weight gain and increased plasma corticosterone
      levels and CRF mRNA expression in the PVN. We also observed an increase in Fos
      CRF and Fos-TH double-labeled neurons after LPS injection in vehicle-pretreated
      rats, with no changes in CART mRNA or Fos-alpha-MSH immunoreactive neurons in the
      ARC. In saline-treated animals, rimonabant pretreatment decreased food intake and
      body weight gain but did not modify hormone response or Fos expression in the
      hypothalamus and brainstem compared with vehicle-pretreated rats. Rimonabant
      pretreatment potentiated LPS-induced hypophagia, body weight loss and Fos-CRF and
      Fos-TH expressing neurons. Rimonabant did not modify corticosterone, CRF mRNA or
      Fos-alpha-MSH responses in rats treated with LPS. These data suggest that the
      endocannabinoid system, mediated by CB1 receptors, modulates hypothalamic and
      brainstem circuitry underlying the hypophagic effect during endotoxemia to
      prevent an exaggerated food intake decrease. This article is part of a Special
      Issue entitled 'Central Control of Food Intake'.

PMID- 22138164
TI  - Glycine reuptake inhibitor RG1678: a pharmacologic characterization of an
      investigational agent for the treatment of schizophrenia.
AB  - Dysfunctional N-methyl-d-aspartate (NMDA) receptor neurotransmission has been
      implicated in the pathophysiology of schizophrenia. It is thought that this
      abnormal functioning can be corrected by increasing availability of the NMDA co
      agonist glycine through inhibition of glycine transporter type 1 (GlyT1). Herein
      is described the pharmacologic profile of RG1678, a potent and noncompetitive
      glycine reuptake inhibitor. In vitro, RG1678 noncompetitively inhibited glycine
      uptake at human GlyT1 with a concentration exhibiting half-maximal inhibition
      (IC(50)) of 25 nM and competitively blocked [(3)H]ORG24598 binding sites at human
      GlyT1b in membranes from Chinese hamster ovary cells. In hippocampal CA1
      pyramidal cells, RG1678 enhanced NMDA-dependent long-term potentiation at 100 nM
      but not at 300 nM. In vivo, RG1678 dose-dependently increased cerebrospinal fluid
      and striatal levels of glycine measured by microdialysis in rats. Additionally
      RG1678 attenuated hyperlocomotion induced by the psychostimulant d-amphetamine or
      the NMDA receptor glycine site antagonist L-687,414 in mice. RG1678 also
      prevented the hyper-response to d-amphetamine challenge in rats treated
      chronically with phencyclidine, an NMDA receptor open-channel blocker. In the
      latter experiment, a decrease in ex vivo striatal [(3)H]raclopride binding was
      also measured. These data demonstrate that RG1678 is a potent, noncompetitive
      glycine reuptake inhibitor that can modulate both glutamatergic and dopaminergic
      neurotransmission in animal experiments that model aspects of schizophrenia. This
      article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

PMID- 22138161
TI  - The evolution of HIV: inferences using phylogenetics.
AB  - Molecular phylogenetics has revolutionized the study of not only evolution but
      also disparate fields such as genomics, bioinformatics, epidemiology, ecology,
      microbiology, molecular biology and biochemistry. Particularly significant are
      its achievements in population genetics as a result of the development of
      coalescent theory, which have contributed to more accurate model-based parameter
      estimation and explicit hypothesis testing. The study of the evolution of many
      microorganisms, and HIV in particular, have benefited from these new
      methodologies. HIV is well suited for such sophisticated population analyses
      because of its large population sizes, short generation times, high substitution
      rates and relatively small genomes. All these factors make HIV an ideal and
      fascinating model to study molecular evolution in real time. Here we review the
      significant advances made in HIV evolution through the application of
      phylogenetic approaches. We first examine the relative roles of mutation and
      recombination on the molecular evolution of HIV and its adaptive response to drug
      therapy and tissue allocation. We then review some of the fundamental questions
      in HIV evolution in relation to its origin and diversification and describe some
      of the insights gained using phylogenies. Finally, we show how phylogenetic
      analysis has advanced our knowledge of HIV dynamics (i.e., phylodynamics).

PMID- 22138165
TI  - Differential regulation of gonadotropin-releasing hormone by corticotropin
      releasing factor family peptides in hypothalamic N39 cells.
AB  - Corticotropin-releasing factor (CRF) is involved in a variety of physiological
      functions including regulation of hypothalamo-pituitary-adrenal axis activity
      during stressful periods. Urocortins (Ucns) are known to be members of the CRF
      family peptides. CRF has a high affinity for CRF receptor type 1 (CRF(1)
      receptor). Both Ucn2 and Ucn3 have very high affinity for CRF receptor type 2
      (CRF(2) receptor) with little or no binding affinity for the CRF(1) receptor.
      Gonadotropin-releasing hormone (GnRH) is known to be involved in the regulation
      of the stress response. Gonadotropin-inhibitory hormone (GnIH) neurons interact
      directly with GnRH neurons, and the action of GnIH is mediated by a novel G
      protein coupled receptor, Gpr147. This study aimed to explore the possible
      function of CRF family peptides and the regulation of GnRH mRNA in hypothalamic
      GnRH cells. Both mRNA and protein expression of the CRF(1) receptor and CRF(2)
      receptor were found in hypothalamic GnRH N39 cells. CRF suppressed GnRH mRNA
      levels via the CRF(1) receptor, while Ucn2 increased the levels via the CRF(2)
      receptor. Both CRF and Ucn2 increased Gpr147 mRNA levels. The results indicate
      that CRF and Ucn2 can modulate GnRH mRNA levels via each specific CRF receptor
      subtype. Finally, CRF suppressed GnRH protein levels, while Ucn2 increased the
      levels. Differential regulation of GnRH by CRF family peptides may contribute to
      the stress response and homeostasis in GnRH cells.

PMID- 22138162
TI  - Dysregulation of brain reward systems in eating disorders: neurochemical
      information from animal models of binge eating, bulimia nervosa, and anorexia
      nervosa.
AB  - Food intake is mediated, in part, through brain pathways for motivation and
      reinforcement. Dysregulation of these pathways may underlay some of the behaviors
      exhibited by patients with eating disorders. Research using animal models of
      eating disorders has greatly contributed to the detailed study of potential brain
      mechanisms that many underlie the causes or consequences of aberrant eating
      behaviors. This review focuses on neurochemical evidence of reward-related brain
      dysfunctions obtained through animal models of binge eating, bulimia nervosa, or
      anorexia nervosa. The findings suggest that alterations in dopamine (DA),
      acetylcholine (ACh) and opioid systems in reward-related brain areas occur in
      response to binge eating of palatable foods. Moreover, animal models of bulimia
      nervosa suggest that while bingeing on palatable food releases DA, purging
      attenuates the release of ACh that might otherwise signal satiety. Animal models
      of anorexia nervosa suggest that restricted access to food enhances the
      reinforcing effects of DA when the animal does eat. The activity-based anorexia
      model suggests alterations in mesolimbic DA and serotonin occur as a result of
      restricted eating coupled with excessive wheel running. These findings with
      animal models complement data obtained through neuroimaging and pharmacotherapy
      studies of clinical populations. Information on the neurochemical consequences of
      the behaviors associated with these eating disorders will be useful in
      understanding these complex disorders and may inform future therapeutic
      approaches, as discussed here. This article is part of a Special Issue entitled
      'Central Control of Food Intake'.

PMID- 22138167
TI  - Nucleosomes stacked with aligned dyad axes are found in native compact chromatin
      in vitro.
AB  - In this study, electron tomograms of plunge-frozen isolated chromatin in both
      open and compacted form were recorded. We have resolved individual nucleosomes in
      these tomograms in order to provide a 3D view of the arrangement of nucleosomes
      within chromatin fibers at different compaction states. With an optimized
      template matching procedure we obtained accurate positions and orientations of
      nucleosomes in open chromatin in "low-salt" conditions (5 mM NaCl). The mean
      value of the planar angle between three consecutive nucleosomes is 70 degrees ,
      and the mean center-to-center distance between consecutive nucleosomes is 22.3
      nm. Since the template matching approach was not effective in crowded conditions,
      for nucleosome detection in compact fibers (40 mM NaCl and 1 mM MgCl(2)) we
      developed the nucleosome detection procedure based on the watershed algorithm,
      followed by sub-tomogram alignment, averaging, and classification by Principal
      Components Analysis. We find that in compact chromatin the nucleosomes are
      arranged with a predominant face-to-face stacking organization, which has not
      been previously shown for native isolated chromatin. Although the path of the DNA
      cannot be directly seen in compact conditions, it is evident that the nucleosomes
      stack with their dyad axis aligned in forming a "double track" conformation which
      is a consequence of DNA joining adjacent nucleosome stacks. Our data suggests
      that nucleosome stacking is an important mechanism for generating chromatin
      compaction in vivo.

PMID- 22138166
TI  - A review of fish-derived antioxidant and antimicrobial peptides: their
      production, assessment, and applications.
AB  - Fishes are rich sources of structurally diverse bioactive compounds. In recent
      years, much attention has been paid to the existence of peptides with biological
      activities and proteins derived from foods that might have beneficial effects for
      humans. Antioxidant and antimicrobial peptides isolated from fish sources may be
      used as functional ingredients in food formulations to promote consumer health
      and improve the shelf life of food products. This paper presents an overview of
      the antioxidant and antimicrobial peptides derived from various fishes. In
      addition, we discuss the extraction of fish proteins, enzymatic production, and
      the techniques used to isolate and characterize these compounds. Furthermore, we
      review the methods used to assay the bioactivities and their applications in food
      and nutraceuticals.

PMID- 22138168
TI  - Effects of cement or lime on Cd, Co, Cu, Ni, Pb, Sb and Zn mobility in field
      contaminated and aged soils.
AB  - Cement or lime can be used to treat trace element contaminated soils, reducing
      their mobility due to increased soil pH which enhances precipitation and
      adsorption, and also due to pozzolanic reactions and cementation. In the present
      work, an alkaline and an acidic soil both containing Cd, Co, Cu, Ni, Pb, Sb and
      Zn from either geogenic or geogenic and anthropogenic origin were treated with
      cement or calcium hydroxide. Soils were then extracted with dilute HNO(3) or NaOH
      solution of different concentrations to obtain extracts of different pH (pH 4
      12). In untreated soils, Co, Cu, Ni and Pb in solutions were detected at alkaline
      pH. The addition of cement or Ca(OH)(2) reduced the mobility of every trace
      element at high pH, but enhanced the mobility of Cd, Co, Cu, Ni, Pb and Zn at low
      pH. Metal mobilisation at high pH was observed for Cu in the acidic soil due to
      the liberation of dissolved organic matter. Below pH 6, Sb mobility was lower in
      the cement-treated soil compared to the untreated soil, but the same in the
      Ca(OH)(2) treated soil as in the control soil. Comparison with theoretical trace
      element precipitates suggested that the mobility of trace elements is likely
      reduced at high pH by encapsulation and immobilisation within the cement matrix
      rather then precipitation.

PMID- 22138169
TI  - Cadmium stabilization with nursery stocks through transplantation: a new approach
      to phytoremediation.
AB  - Disposal of heavy metal contaminated biomass after phytoremediation is still
      unfeasible. This paper presents a viable phyto-extraction approach in which
      metals in contaminated soils are stabilized by nursery stocks before
      transplantation for greening. In this respect, two pot-experiments are reported
      comparing seven nursery stocks species exposed to different Cd levels. The first
      experiment revealed that Cd was mainly stabilized in the roots of all species
      studied. Greater amounts of Cd were accumulated in the epidermis than cortex plus
      stele. Cupressus Blue Ice showed greatest tolerance to the 100 and 200 mg kg(-1)
      Cd stresses. The second experiment additionally evaluated the possible risk of Cd
      release after transplanting the Cd treated plants into uncontaminated soil. After
      120 days of transplantation, the relatively trace amounts of Cd in the roots of
      Euonymus japonicus, Pittosporum tobira and C. Blue Ice had either been partially
      transferred into the shoots or released into the soil. The highest Cd
      concentration increase in bulk soil (0.428 mg kg(-1)), however, was much lower
      than the environmental quality standard for soils of China (1 mg kg(-1)). The
      potential effectiveness of this technique in the use of Cd-contaminated soil and
      further investigation needed in the field trials were also evaluated.

PMID- 22138170
TI  - Characterization and assessment of chemical modifications of metal-bearing
      sludges arising from unsuitable disposal.
AB  - Ettringite-gypsum sludge, formed by neutralization of acid mine drainage with
      lime, has been stored temporarily in the open pit of a uranium mine that floods
      periodically. The present study characterized samples of this sludge, named
      according to the time of placement as Fresh, Intermediate, and Old. Standard
      leaching and sequential extraction procedures assessed the associations and
      stabilities of U, Zn, Fe, Mn, and other contaminants in the solid phases.
      Corresponding mineralogical transformations associated with sludge weathering
      were modeled using PHREEQC. The main crystalline phases were ettringite, gypsum
      and calcite; the minor constituents were fluorite and gibbsite. This mineral
      assemblage could be attributed to the incongruent dissolution of ettringite to
      form gibbsite, calcite, and gypsum. Sequential extractions indicated high
      contents of U, Ca, SO(4), and Zn in the water-soluble (exchangeable) and
      carbonate fractions. Thus, the analytical and modeling results indicated that
      despite being classified as non-toxic by standard leaching protocols, the
      minerals composing the sludge could be sources of dissolved F, SO(4), Fe, Zn, Mn,
      U, and Al under various environmental conditions. Decommissioning strategies
      intended to prevent contaminant migration will need to consider the chemical
      stability of the sludge in various environments.

PMID- 22138171
TI  - Enhanced dechlorination of trichloroethylene using electrospun polymer
      nanofibrous mats immobilized with iron/palladium bimetallic nanoparticles.
AB  - Fe/Pd bimetallic nanoparticles (NPs) have held great promise for treating
      trichloroethylene (TCE)-contaminated groundwater, without the accumulation of
      chlorinated intermediates. However, the conventionally used colloidal Fe/Pd NPs
      usually aggregate rapidly, resulting in a reduced reactivity. To reduce the
      particle aggregation, we employed electrospun polyacrylic acid (PAA)/polyvinyl
      alcohol (PVA) polymer nanofibers as a nanoreactor to immobilize Fe/Pd bimetallic
      NPs. In the study, the water-stable PAA/PVA nanofibrous mats were complexed with
      Fe (III) ions via the binding with the free carboxyl groups of PAA for subsequent
      formation and immobilization of zero-valent iron (ZVI) NPs. Fe/Pd bimetallic NPs
      were then formed by the partial reduction of Pd(II) ions with ZVI NPs. The formed
      electrospun nanofibrous mats containing Fe/Pd bimetallic NPs with a diameter of
      2.8 nm were characterized by scanning electron microscopy, energy-dispersive
      spectroscopy, transmission electron microscopy, thermogravimetric analysis, and
      inductively coupled plasma-atomic emission spectroscopy. The Fe/Pd NP-containing
      electrospun PAA/PVA nanofibrous mats exhibited higher reactivity than that of the
      ZVI NP-containing mats or colloidal Fe/Pd NPs in the dechlorination of
      trichloroethylene (TCE), which was used as a model contaminant. With the high
      surface area to volume ratio, high porosity, and great reusability of the fibrous
      mats immobilized with the bimetallic NPs, the composite nanofibrous mats should
      be amenable for applications in remediation of various environmental
      contaminants.

PMID- 22138173
TI  - Effects of the interaction of TiO2 nanoparticles with bisphenol A on their
      physicochemical properties and in vitro toxicity.
AB  - In this paper we evaluated the effects of the interaction of TiO(2) nanoparticles
      (nano-TiO(2)) with bisphenol A (BPA) on their physicochemical properties and in
      vitro toxicity in human embryo L-02 hepatocytes. Different concentrations of BPA
      (0, 0.1, 1, 10 MUmol/L) and nano-TiO(2) (0, 0.1, 1, 10mg/L) were mixed to analyze
      the size distribution, zeta potential, adsorption capacity and uptake of nano
      TiO(2), and the toxicity of nano-TiO(2) and BPA in L-02 cells. The addition of
      BPA to nano-TiO(2) dispersions increased the aggregation level and zeta potential
      of nano-TiO(2) in all media. Nano-TiO(2) had a similar adsorption capacity in
      different media, although a higher aggregation level was observed in cell culture
      medium. Nano-TiO(2), with or without BPA, could enter L-02 cells after 24h
      exposure. Nano-TiO(2) alone did not induce significant DNA and chromosome damage,
      but the mixture of nano-TiO(2) and BPA increased toxicity via increasing
      oxidative stress, DNA double strand breaks and micronuclei formation. The
      aggregated nano-TiO(2) can enrich BPA effectively. The BPA-bound nano-TiO(2) are
      proven to be uptaken into nuclei of exposed cells, which may increase
      intracellular BPA and nano-TiO(2) levels and thus lead to synergistic toxicity.
      However only small synergic effects were observed at the concentrations of BPA
      and nano-TiO(2) used in this study.

PMID- 22138172
TI  - Research on soot of black smoke from ceramic furnace flue gas: characterization
      of soot.
AB  - In this study, the characterizations of soot from ceramic furnace flue gas were
      studied using environmental scanning electron microscopy, energy dispersive
      spectroscopy, particle size distribution, specific surface area measurements,
      crystal characterizations and organic pollutant analysis. Soot particles were
      mainly spherical nanoparticles with diameters less than 100 nm. However, the
      particles could be aggregated into larger ones with a median diameter of 3.66
      MUm. Nanometer pores with diameters ranging 2-4 nm were also detected in the soot
      particles. Because of their large surface areas and pore volumes, other
      pollutants in the environment can be adsorbed to soot particles potentially
      making them more hazardous. Several elements, including C, O and Pb, were
      detected in the soot, but only small amounts of crystalline materials were
      observed. This is because most of the detected carbon and metals/metal
      oxides/metal salts were amorphous. Approximately 90 different organic pollutants
      were detected in the soot, including aromatic compounds and other hydrocarbons.
      Because of the carcinogenic properties of aromatic compounds and the
      photochemical effects of hydrocarbons, soot could have serious health and
      environmental impacts. The results suggest that soot particles are hazardous
      material and urgently need to be controlled.

PMID- 22138174
TI  - Calcium water treatment residue reduces copper phytotoxicity in contaminated
      sandy soils.
AB  - Calcium water treatment residue (Ca-WTR), an industrial by-product, was found to
      be effective in decreasing Cu availability in contaminated soils and transport to
      the environment. In this study, a greenhouse study was conducted to test the
      ability of Ca-WTR to reduce the toxicity and uptake of Cu by ryegrass (Lolium
      perenne L.) and lettuce (Lactuca sativa L.) as indicator crop plants in Cu
      contaminated sandy soils. Eight weeks growing period was observed in Alfisol and
      Spodosol amended with different levels of Ca-WTR (5-100 g kg(-1) soil). Plant
      biomass yields increased with WTR application rates at the low levels (5-20 g kg(
      1) for Alfisol, pH 5.45 and 5-50 g kg(-1) for Spodosol, pH 4.66), and decreased
      at the high levels (>20 g kg(-1) for Alfisol and >50 g kg(-1) for Spodosol). The
      maximum growth of ryegrass with Ca-WTR was 133% and 149% of the control (without
      Ca-WTR) for the original Alfisol and Spodosol (without spiked Cu), respectively,
      while the corresponding values for lettuce was 145% and 206%. Copper
      concentrations in ryegrass shoots decreased significantly with increasing Ca-WTR
      application rates. For lettuce, Cu concentration decreased only at high Ca-WTR
      rates (>50 g kg(-1)). In addition, ryegrass had a greater potential for Cu uptake
      and translocation than lettuce in both soils.

PMID- 22138175
TI  - Thermal degradation of Fenitrothion: identification and eco-toxicity of
      decomposition products.
AB  - The thermal decomposition of Fenitrothion [phosphorothioic acid O,O-diethyl O-(3
      methyl-4-nitrophenyl) ester] was investigated. Results obtained by different
      scale calorimetric techniques show that the thermal decomposition of Fenitrothion
      involves two main steps. Intermediate and final thermal degradation products
      formed during isothermal and adiabatic thermal decomposition experiments were
      identified. The eco-toxicological profile of the decomposition products was
      assessed experimentally and compared to results obtained with a predictive
      software (ECOSAR). A specific index was defined to assess the change in
      ecotoxicity profile of decomposition products with respect to the original
      compound.

PMID- 22138176
TI  - ZnS nanocrystals and nanoflowers synthesized by a green chemistry approach: rare
      excitonic photoluminescence achieved by the tunable molar ratio of precursors.
AB  - In the present work, we demonstrated a simple and green synthesis route for shape
      controlled ZnS nanocrystals, where only environmentally benign chemicals, namely
      sulfur, zinc oxide and olive oil, were employed. By controlling the experimental
      conditions, we were able to tune the band edge and trap state photoluminescences
      of ZnS nanocrystals and obtain pure excitonic photoluminescence that was rarely
      observed in literature. The trap state emission was derived from sulfur vacancies
      and would be eliminated when an excess of sulfur was used during the synthesis.
      Additionally, the morphology of ZnS nanocrystals could be tuned to appear like
      flowers, where the formation mechanism was systematically discussed.

PMID- 22138177
TI  - An additional oligosaccharide moiety in the HA of a pandemic influenza H1N1
      candidate vaccine virus confers increased antigen yield in eggs.
AB  - The H1N1 influenza pandemic in 2009 highlighted the need for the rapid generation
      of candidate vaccine viruses (CVVs) against an A/California/7/2009-like virus.
      The first available CVVs gave low protein yields in eggs but improved yields were
      achieved for second generation CVVs which contained amino acid substitutions
      compared to their precursor viruses. In this study, we investigated the basis for
      the increased virus protein yield of CVV NIBRG-121xp and whether the improved
      yield characteristics could be transferred between this virus and two other CVVs,
      NYMC X-179A and NYMC X-181. We generated variant viruses by reverse genetics to
      contain combinations of amino acid substitutions found in high yielding NIBRG
      121xp and NYMC X-181. We found that the increase in total protein yield and
      functional HA yield of NIBRG-121xp in eggs is attributable to the single amino
      acid substitution K119N in the HA. We also found that the glycosylation of
      position 119 is essential for the improved virus protein yield in eggs. However,
      the K119N yield-enhancing effect was not transferable between viruses, nor was
      the N129D change found in high yielding NYMC X-181. However, position 119 may be
      a useful locus to monitor in future for viruses and CVVs with potentially high
      yield.

PMID- 22138178
TI  - Saponin-based adjuvants create a highly effective anti-tumor vaccine when
      combined with in situ tumor destruction.
AB  - Today's most commonly used microbial vaccines are essentially composed of
      antigenic elements and a non-microbial adjuvant, and induce solid amounts of
      antibodies. Cancer vaccines mostly aim to induce anti-tumor CTL-responses, which
      require cross-presentation of tumor-derived antigens by dendritic cells (DCs).
      Adjuvants that improve DC function and antigen cross-presentation are therefore
      advantageous for inducing anti-tumor immunity. Previously, we have reported that
      in situ tumor destruction of established murine tumors by ablation efficiently
      delivers antigens to DC for the in vivo induction of anti-tumor immunity. Yet,
      tumor ablation alone resulted in only partial protection against a subsequent
      tumor-challenge. In this article, the ability of various non-microbial vaccine
      adjuvants to modulate the immune response following cryo-ablation was tested. The
      data show that tumor ablation with co-injection of saponin-based adjuvants, but
      not oil-in-water, water-in-oil or alum-based adjuvants, creates a highly
      effective in situ vaccine. Draining lymph node CD11c+ DCs acquire antigens more
      efficiently and become increasingly activated following ablation with saponin
      adjuvants relative to ablation alone. Moreover, our data reveal that the saponin
      based adjuvants facilitate an in this model unprecedented level of antigen cross
      presentation, induction of tumor-specific CTL and long-lasting tumor protection.
      Collectively, combining saponin-based adjuvants with in situ tumor destruction
      leads to an extremely potent systemic anti-tumor response. This combination
      approach forms a powerful in situ DC vaccine for which no prior knowledge of
      tumor antigens is required. As saponin-based adjuvants are currently clinically
      available, they represent attractive tools for various human and veterinary
      settings where in situ tumor destruction is applied.

PMID- 22138180
TI  - Pain perception in humans: use of intraepidermal electrical stimulation.
AB  - The choice of a system specific stimulus is difficult when investigating the
      human nociceptive system, in contrast with the tactile, auditory and visual
      systems, because it should be noxious but not actually damage the tissue. The
      discomfort accompanying system specific stimulation must be kept to a minimum for
      ethical reasons. In this review, recent progress made in the study of human pain
      perception using intraepidermal electrical stimulation (IES) is described. Also,
      whether IES is a viable alternative to laser stimulation is discussed. IES
      selectively activates Adelta nociceptors, elicits a sharp pricking sensation with
      minimal discomfort and evokes cortical responses almost identical to those
      produced by laser stimulation. As IES does not require expensive equipment, and
      is easy to control, it would seem useful for pain research as well as clinical
      tests.

PMID- 22138179
TI  - Carotid body growth during chronic postnatal hyperoxia.
AB  - Rats reared in hyperoxia have smaller carotid bodies as adults. To study the time
      course and mechanisms underlying these changes, rats were reared in 60% O(2) from
      birth and their carotid bodies were harvested at various postnatal ages (P0-P7,
      P14). The carotid bodies of hyperoxia-reared rats were smaller than those of age
      matched controls beginning at P4. In contrast, 7d of 60% O(2) had no effect on
      carotid body size in rats exposed to hyperoxia as adults. Bromodeoxyuridine
      (BrdU) and TdT-mediated dUTP nick end labeling (TUNEL) were used to assess cell
      proliferation and DNA fragmentation at P2, P4, and P6. Hyperoxia reduced the
      proportion of glomus cells undergoing cell division at P4; although a similar
      trend was evident at P2, hyperoxia no longer affected cell proliferation by P6.
      The proportion of TUNEL-positive glomus cells was modestly increased by
      hyperoxia. We did not detect changes in mRNA expression for proapoptotic (Bax) or
      antiapoptotic (Bcl-X(L)) genes or transcription factors that regulate cell cycle
      checkpoints (p53 or p21), although mRNA levels for cyclin B1 and cyclin B2 were
      reduced. Collectively, these data indicate that hyperoxia primarily attenuates
      postnatal growth of the carotid body by inhibiting glomus cell proliferation
      during the first few days of exposure.

PMID- 22138181
TI  - Molecular pathogenesis of Parkinson's disease: update.
AB  - Parkinson disease (PD) is a neurodegenerative disease characterised by
      progressive disturbances in motor, autonomic and psychiatric functions. Much has
      been learnt since the disease entity was established in 1817. Although there are
      well established treatments that can alleviate the symptoms of PD, a pressing
      need exists to improve our understanding of the pathogenesis to enable
      development of disease modifying treatments. Ten responsible genes for PD have
      been identified and recent progress in molecular research on the protein
      functions of the genes provides new insights into the pathogenesis of hereditary
      as well as sporadic PD. Also, genome wide association studies, a powerful
      approach to identify weak effects of common genetic variants in common diseases,
      have identified a number of new possible PD associated genes, including PD genes
      previously detected. However, there is still much to learn about the interactions
      of the gene products, and important insights may come from chemical and genetic
      screens. In this review, an overview is provided of the molecular pathogenesis
      and genetics of PD, focusing particularly on the functions of the PD related gene
      products with marked research progress.

PMID- 22138182
TI  - Tristetraprolin down-regulates IL-17 through mRNA destabilization.
AB  - An excess of interleukin 17 (IL-17) may contribute to chronic inflammatory
      disorders, but mechanisms that regulate IL-17 in immune cells are unclear. Here
      we report that tristetraprolin (TTP) inhibits IL-17 production in human T cell
      lines. Overexpression of TTP decreased the expression of IL-17. Conversely, TTP
      inhibition by siRNA increased IL-17 production. IL-17 mRNA contains eight AREs
      within its 3'UTR. TTP bound directly to the IL-17 mRNA 3'UTR at a location
      between the fourth and seventh AREs and enhanced decay of IL-17 transcripts.
      These results suggest that TTP could control IL-17-mediated inflammation.

PMID- 22138183
TI  - Proteostasis of tau. Tau overexpression results in its secretion via membrane
      vesicles.
AB  - Increasing amounts of tau protein were expressed in non-neuronal cells. When
      intracellular amounts reached a threshold level, tau protein was released to the
      extracellular culture medium in association with membrane vesicles. Hence, we
      propose that tau might be secreted through membrane vesicles as a cellular
      mechanism to eliminate the excess of tau protein, thereby avoiding its toxicity.

PMID- 22138184
TI  - The protein chaperone Ssa1 affects mRNA localization to the mitochondria.
AB  - Many nuclear-transcribed mRNAs encoding mitochondrial proteins are localized near
      the mitochondrial outer membrane. A yet unresolved question is whether protein
      synthesis is important for transport of these mRNAs to their destination. Herein
      we present a connection between mRNA localization in yeast and the protein
      chaperone Ssa1. Ssa1 depletion lowered mRNA association with mitochondria while
      its overexpression increased it. A genome-wide analysis revealed that Ssa
      proteins preferentially affect mRNAs encoding hydrophobic proteins, which are
      expected targets for these protein chaperones. Importantly, deletion of the
      mitochondrial receptor Tom70 abolished the impact of Ssa1 overexpression on mRNAs
      encoding Tom70 targets. Taken together, our results suggest a role for Ssa1 in
      mediating localization of nascent peptide-ribosome-mRNA complexes to the
      mitochondria, consistent with a co-translational transport process.

PMID- 22138185
TI  - A dye binding method for measurement of total protein in microalgae.
AB  - Protein is a large component of the standing biomass of algae. The total protein
      content of algae is difficult to measure because of the problems encountered in
      extracting all of the protein from the cells. Here we modified an existing
      protein assay to measure total protein in microalgae cells that involves little
      or no extraction of protein from the cells. Aliquots of fresh or pretreated cells
      were spotted onto filter paper strips. After drying, the strips were stained in a
      0.1% (w/v) solution of the protein stain Coomassie Brilliant Blue R-250 for 16 to
      24 h and then destained. The stained protein spots were cut out from the paper,
      and dye was eluted in 1% (w/v) sodium dodecyl sulfate (SDS). Absorbance at 600 nm
      was directly proportional to protein concentration. Cells that were recalcitrant
      to taking up the dye could be either heated at 80 degrees C for 10 min in 1% SDS
      or briefly sonicated for 3 min to facilitate penetration of the dye into the
      cells. Total protein measured in Chlorella vulgaris using this method compared
      closely with that measured using the total N method. Total protein concentrations
      were measured successfully in 12 algal species using this dye binding method.

PMID- 22138186
TI  - Selection of single-chain variable fragment antibodies against fenitrothion by
      ribosome display.
AB  - A single-chain variable fragment (ScFv) complementary DNA (cDNA) library against
      fenitrothion was constructed, and ScFvs specific for fenitrothion were selected
      by ribosome display from the library. After three rounds of ribosome display, the
      ScFv genes were cloned into Escherichia coli for expression. The expressed ScFvs
      of 160 clones were analyzed by indirect enzyme-linked immunosorbent assay
      (ELISA). Of these, 40 clones produced antibodies with relatively high activity
      against fenitrothion, and 3 were selected for Biacore and ELISA analysis. These 3
      antibodies-ScFv-AF50, ScFv-AF93, and ScFv-AF132-had IC(50) values of 1.6, 3.4,
      and 2.2 ng/ml, respectively. Cross-reactivity with other organophosphorus (OP)
      pesticides was below 0.1% except for parathion-methyl (<=2.8%). The IC(50) values
      and cross-reactivity were lower than achieved previously with polyclonal or
      monoclonal antibodies against fenitrothion. The equilibrium dissociation constant
      (K(D)) values determined by Biacore analysis were 4.56*10(-10)M for ScFv-AF50,
      1.42*10(-9)M for ScFv-AF93, and 2.66*10(-10)M for ScFv-AF132. These results
      demonstrate that the ribosome display has great potential in selection of ScFvs
      against pesticides. Recoveries of fenitrothion from fortified rice and cucumber
      were in the range 80.6 to 108%, indicating that the ELISAs with the isolated
      ScFvs can accurately determine fenitrothion in food samples after the simple and
      rapid extraction procedure.

PMID- 22138187
TI  - The function of secretory IgA in the context of the intestinal continuum of
      adaptive immune responses in host-microbial mutualism.
AB  - The large production of immunoglobulin (Ig)A is energetically costly. The fact
      that evolution retained this apparent luxury of intestinal class switch
      recombination to IgA within the human population strongly indicates that there
      must be a critical specific function of IgA for survival of the species. The
      function of IgA has been investigated in a series of different models that will
      be discussed here. While IgA has clear protective functions against toxins or in
      the context of intestinal viral infections, the function of IgA specific for non
      pathogenic commensal bacteria remains unclear. In the context of the current
      literature we present a hypothesis where secretory IgA integrates as an
      additional layer of immune function into the continuum of intestinal CD4 T cell
      responses, to achieve a mutualistic relationship between the intestinal commensal
      microbiota and the host.

PMID- 22138188
TI  - The mammalian intestinal epithelium as integral player in the establishment and
      maintenance of host-microbial homeostasis.
AB  - Only one single layer of epithelial cells separates the densely colonized and
      environmentally exposed intestinal lumen from the largely sterile subepithelial
      tissue. Together with the overlaying mucus and the subepithelial mucosal immune
      system the epithelium has evolved to maintain homeostasis in the presence of the
      enteric microbiota. It also contributes to rapid and efficient antimicrobial host
      defence in the event of infection with pathogenic microorganisms. Both,
      epithelial antimicrobial host defence and homeostasis rely on signalling pathways
      induced by innate immune receptors demonstrating the active role of epithelial
      cells in the host-microbial interplay. The interaction of epithelial cells with
      professional immune cells illustrates the integrated function within the mucosal
      tissue. In the present review we focus on structural and functional changes of
      the intestinal epithelium during the fetal-neonatal transition and infancy and
      try to delineate its role in the induction and maintenance of host-microbial
      homeostasis. We also address factors that impair epithelial functions and may
      lead to disruption of the mucosal barrier, tissue damage and the development of
      symptomatic disease.

PMID- 22138189
TI  - Hepatitis C virus infects the endothelial cells of the blood-brain barrier.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) infection leads to progressive liver
      disease and is associated with a variety of extrahepatic syndromes, including
      central nervous system (CNS) abnormalities. However, it is unclear whether such
      cognitive abnormalities are a function of systemic disease, impaired hepatic
      function, or virus infection of the CNS. METHODS: We measured levels of HCV RNA
      and expression of the viral entry receptor in brain tissue samples from 10
      infected individuals (and 3 uninfected individuals, as controls) and human brain
      microvascular endothelial cells by using quantitative polymerase chain reaction
      and immunochemical and confocal imaging analyses. HCV pseudoparticles and cell
      culture-derived HCV were used to study the ability of endothelial cells to
      support viral entry and replication. RESULTS: Using quantitative polymerase chain
      reaction, we detected HCV RNA in brain tissue of infected individuals at
      significantly lower levels than in liver samples. Brain microvascular endothelia
      and brain endothelial cells expressed all of the recognized HCV entry receptors.
      Two independently derived brain endothelial cell lines, hCMEC/D3 and HBMEC,
      supported HCV entry and replication. These processes were inhibited by antibodies
      against the entry factors CD81, scavenger receptor BI, and claudin-1; by
      interferon; and by reagents that inhibit NS3 protease and NS5B polymerase. HCV
      infection promotes endothelial permeability and cellular apoptosis. CONCLUSIONS:
      Human brain endothelial cells express functional receptors that support HCV entry
      and replication. Virus infection of the CNS might lead to HCV-associated
      neuropathologies.

PMID- 22138191
TI  - The mechanism of action of doxofylline is unrelated to HDAC inhibition, PDE
      inhibition or adenosine receptor antagonism.
AB  - Xanthines such as theophylline have been used in the treatment of lung diseases
      since the early 1900's, but have a major drawback of a very narrow therapeutic
      window and many drug/drug interactions. This means that plasma levels have to be
      measured regularly and can make the use of theophylline problematic. With the
      increasing availability of other classes of drugs for the treatment of
      respiratory diseases, this has limited the use of xanthines, despite their clear
      clinical benefit in the treatment of patients with asthma and COPD. Doxofylline
      is a xanthine molecule having both bronchodilator and anti-inflammatory activity
      with an improved therapeutic window over conventional xanthines such as
      theophylline. However, the mechanistic basis of this improved therapeutic window
      is not understood. The present study has investigated some pharmacological
      activities of doxofylline in comparison with theophylline. Doxofylline does not
      directly inhibit any of the known HDAC enzymes, and did not inhibit any PDE
      enzyme sub types or act as an antagonist at any of the known adenosine receptors,
      except for PDE2A(1), and adenosine A(2A) and only at the highest tested
      concentration (10(-4) M). These results may explain the improved tolerability
      profile of doxofylline compared with theophylline.

PMID- 22138190
TI  - Fibromodulin, an oxidative stress-sensitive proteoglycan, regulates the
      fibrogenic response to liver injury in mice.
AB  - BACKGROUND & AIMS: Collagen I deposition contributes to liver fibrosis, yet
      little is known about other factors that mediate this process. Fibromodulin is a
      liver proteoglycan that regulates extracellular matrix organization and is
      induced by fibrogenic stimuli. We propose that fibromodulin contributes to the
      pathogenesis of fibrosis by regulating the fibrogenic phenotype of hepatic
      stellate cells (HSCs). METHODS: We analyzed liver samples from patients with
      hepatitis C-associated cirrhosis and healthy individuals (controls). We used a
      coculture model to study interactions among rat HSCs, hepatocytes, and sinusoidal
      endothelial cells. We induced fibrosis in livers of wild-type and Fmod(-/-) mice
      by bile duct ligation, injection of CCl(4), or administration of thioacetamide.
      RESULTS: Liver samples from patients with cirrhosis had higher levels of
      fibromodulin messenger RNA and protein than controls. Bile duct ligation, CCl(4),
      and thioacetamide each increased levels of fibromodulin protein in wild-type
      mice. HSCs, hepatocytes, and sinusoidal endothelial cells produced and secreted
      fibromodulin. Infection of HSCs with an adenovirus that expressed fibromodulin
      increased expression of collagen I and alpha-smooth muscle actin, indicating
      increased activation of HSCs and fibrogenic potential. Recombinant fibromodulin
      promoted proliferation, migration, and invasion of HSCs, contributing to their
      fibrogenic activity. Fibromodulin was sensitive to reactive oxygen species. HepG2
      cells that express cytochrome P450 2E1 produced fibromodulin, and HSCs increased
      fibromodulin production in response to pro-oxidants. In mice, administration of
      an antioxidant prevented the increase in fibromodulin in response to CCl(4).
      Coculture of hepatocytes or sinusoidal endothelial cells with HSCs increased the
      levels of reactive oxygen species in the culture medium, along with collagen I
      and fibromodulin proteins; this increase was prevented by catalase. Fibromodulin
      bound to collagen I, but the binding did not prevent collagen I degradation by
      matrix metalloproteinase 13. Bile duct ligation caused liver fibrosis in wild
      type but not Fmod(-/-) mice. CONCLUSIONS: Fibromodulin levels are increased in
      livers of patients with cirrhosis. Hepatic fibromodulin activates HSCs and
      promotes collagen I deposition, which leads to liver fibrosis in mice.

PMID- 22138192
TI  - Anatomical and dose changes of gross tumour volume and parotid glands for head
      and neck cancer patients during intensity-modulated radiotherapy: effect on the
      probability of xerostomia incidence.
AB  - AIMS: To quantify the changes in dose as well as in the prediction of parotid
      gland toxicity due to anatomical changes during therapy of head and neck cancer
      patients. MATERIALS AND METHODS: Fifteen patients with advanced locoregional head
      and neck cancer, with no evidence of distant metastasis, were enrolled in a
      prospective study. All patients were treated with intensity-modulated
      radiotherapy. Multiple computed tomography scans were repeated at the end of each
      treatment week. The original treatment plans were copied to the per-treatment
      scans to create hybrid plans. The normal tissue complication probability (NTCP)
      was calculated assuming the end point to be grade >=3 xerostomia according to the
      Radiation Therapy Oncology Group late toxicity scale. RESULTS: The gross tumour
      volume dose coverage was slightly affected by the anatomical changes, whereas the
      mean dose (D(mean)) to the parotids changed from 26.1 +/- 6.0 to 27.4 +/- 7.4 Gy,
      with a mean increase of 0.22 Gy/treatment week. Consequently, the mean NTCP
      increased from 0.15 +/- 0.06 to 0.18 +/- 0.10, primarily due to a few patients
      exhibiting a marked increase. The absolute gross tumour volume shrinkage and the
      percentage parotids shrinkage were the best independent predictors for the NTCP
      variations. CONCLUSIONS: On average, the increase in the parotids D(mean) as well
      as in NTCP during treatment is limited, and the observed variations were strongly
      patient-dependent.

PMID- 22138193
TI  - The 3D in vivo Achilles' tendon moment arm, quantified during active muscle
      control and compared across sexes.
AB  - The Achilles' tendon moment arm (ATma) is a critical quantity in that it defines
      the triceps surae's ability to generate a moment on the calcaneus, which is then
      transferred to the foot. This measure has been primarily acquired two
      dimensionally in small male populations. Thus, the primary purpose of this study
      was to establish the first in vivo three-dimensional measures of the ATma,
      measured non-invasively during dynamic activity in a large normative population,
      inclusive of both males and female subjects (n=20). Subjects were each placed
      supine in a 1.5 T MRI and asked to repeat a simulated toe-raise while a full
      sagittal-cine-phase contrast (dynamic) MRI dataset was acquired. From these data,
      the 3D and 2D ATma was calculated. The ATma was scaled by the distal tibial
      width, based on a correlation analysis. The 2D ATma overestimated its 3D
      counterpart by 3.1 mm, on average. The scaled ATma was no different between the
      male and female cohorts, but the scaled Achilles' tendon area was smaller in the
      male cohort. The magnitudes of the ATma were most similar to previously reported
      values when variations in ankle angle were taken into account. The results of
      this study have important implications for the applicability of ATma data to both
      clinical questions and modeling. Any future studies should adapt the ATma based
      on subject size and/or sex, ensure compatibility between the manner in which the
      ankle angle is defined and the data being used, and account for the influence
      that muscle force has on the 3D ATma.

PMID- 22138194
TI  - Validation of a 3D computational fluid-structure interaction model simulating
      flow through an elastic aperture.
AB  - This work presents a validation of a fluid-structure interaction computational
      model simulating the flow conditions in an in vitro mock heart chamber modeling
      mitral valve regurgitation during the ejection phase during which the trans
      valvular pressure drop and valve displacement are not as large. The mock heart
      chamber was developed to study the use of 2D and 3D color Doppler techniques in
      imaging the clinically relevant complex intra-cardiac flow events associated with
      mitral regurgitation. Computational models are expected to play an important role
      in supporting, refining, and reinforcing the emerging 3D echocardiographic
      applications. We have developed a 3D computational fluid-structure interaction
      algorithm based on a semi-implicit, monolithic method, combined with an arbitrary
      Lagrangian-Eulerian approach to capture the fluid domain motion. The mock
      regurgitant mitral valve corresponding to an elastic plate with a geometric
      orifice, was modeled using 3D elasticity, while the blood flow was modeled using
      the 3D Navier-Stokes equations for an incompressible, viscous fluid. The two are
      coupled via the kinematic and dynamic conditions describing the two-way coupling.
      The pressure, the flow rate, and orifice plate displacement were measured and
      compared with numerical simulation results. In-line flow meter was used to
      measure the flow, pressure transducers were used to measure the pressure, and a
      Doppler method developed by one of the authors was used to measure the axial
      displacement of the orifice plate. The maximum recorded difference between
      experiment and numerical simulation for the flow rate was 4%, the pressure 3.6%,
      and for the orifice displacement 15%, showing excellent agreement between the
      two.

PMID- 22138195
TI  - On the role of membrane anisotropy and BAR proteins in the stability of tubular
      membrane structures.
AB  - Recent studies have demonstrated that actin filaments are not crucial for the
      short-term stability of tubular membrane protrusions originating from the cell
      surface. It has also been demonstrated that prominin nanodomains and curvature
      inducing I-BAR proteins could account for the stability of the membrane
      protrusion. Here we constructed an axisymmetric model of a membrane protrusion
      that excludes actin filaments in order to investigate the contributions of
      prominin nanodomains (rafts) and I-BAR proteins to the membrane protrusion
      stability. It was demonstrated that prominin nanodomains and I-BAR proteins can
      stabilize the membrane protrusion only over a specific range of spontaneous
      curvature. On the other hand, high spontaneous curvature and/or high density of I
      BAR proteins could lead to system instability and to non-uniform contraction in
      the radial direction of the membrane protrusion. In agreement with previous
      studies, it was also shown that the isotropic bending energy of lipids is not
      sufficient to explain the stability of the observed tubular membrane protrusion
      without actin filaments.

PMID- 22138196
TI  - Reversible male infertility under treatment with an anti-TNFalpha agent: a case
      report.

PMID- 22138197
TI  - Intravenous CDP-choline activates neurons in supraoptic and paraventricular
      nuclei and induces hormone secretion.
AB  - The aim of the present study was to assess the effects of intravenous (i.v.)
      cytidine-5'-diphosphate (CDP)-choline administration on the activation of
      oxytocin and vasopressin neurons in the supraoptic (SON) and paraventricular
      nuclei (PVN), using the immunohistochemical identification of c-Fos expression as
      a marker of neuronal activation and to correlate this with the plasma hormone
      levels. Rats were catheterized under sevofluorane anesthesia and experiments were
      conducted 24h later. Blood samples were withdrawn from arterial catheter at 2, 5,
      10, 20, 40 and 60 min after CDP-choline (0.5, 1.0 and 2.0 g/kg; i.v.) or saline
      (1.0 ml/kg; i.v.) for the measurement of plasma oxytocin and vasopressin levels
      by radioimmunoassay. Animals were sacrificed 90 min after CDP-choline
      administration for dual immunohistochemistry which was performed on
      paraformaldehyde-fixed vibratome sections. Dual immunohistochemistry for c-Fos
      and oxytocin or vasopressin revealed that CDP-choline activates these neurons in
      a dose-dependent manner. Light microscopic analyses showed that, about 41%, 75%
      or 87% of the oxytocin neurons and about 18%, 46% or 82% of the vasopressin
      neurons in SON express c-Fos, thus activated, by the dosages of 0.5, 1.0 or 2.0
      g/kg CDP-choline, respectively. Increases in c-Fos expression were about 29%, 62%
      or 81% for the oxytocin neurons and about 38%, 70% or 78% for the vasopressin
      neurons in PVN with the dosages of 0.5, 1.0 or 2.0 g/kg CDP-choline,
      respectively. When compared to the control groups (8% and 7% oxytocin or 2% and
      5% vasopressin neuronal activation in SON or PVN, respectively), these increases
      were found to be statistically significant (p<0.05). In the PVN most of the
      magnocellular neurons were activated while less number of parvocellular neurons
      expressed c-Fos in response to CDP-choline challenge. In correlation with c-Fos
      data, CDP-choline increased plasma oxytocin and vasopressin levels both dose- and
      time-dependently. Results of the present study suggested that peripheral
      administration of CDP-choline is able to increase plasma oxytocin and vasopressin
      levels while activating the respective neurons.

PMID- 22138198
TI  - Effects of COMT polymorphisms on brain function and behavior in health and
      disease.
AB  - The catechol-O-methyltransferase (COMT) gene has attracted strong neuroscientific
      interest due to its implication in dopaminergic neurotransmission. One of its
      most widely studied variations comprises a common single nucleotide polymorphism
      (SNP), a valine-to-methionine substitution at codon 158 (COMT Val158Met), which
      has been associated with various cognitive phenotypes, psychiatric disorders and
      changes in brain activation and structure. This review first gives an overview of
      recent findings on the effect of COMT Val158Met carrier status on behavioral and
      imaging correlates of brain function. Here, we highlight not only commonalities
      but also disparate findings and open questions, and identify possible causal
      factors including gender effects, study population characteristics, and
      definition of the respective phenotypes. Next, an introduction to what is known
      about interactions of COMT allele carrier status with age and environment is
      provided. The review closes with a discussion of the impact of additional COMT
      polymorphisms on brain structure and function, as well as gene-gene interactions
      between COMT and other learning-relevant genes. Future studies should try to
      disentangle the complex effects of COMT Val158Met on brain functions by taking
      gender, age, ethnicity, endophenotypes, as well as gene-environment and gene-gene
      interactions into account.

PMID- 22138199
TI  - A multilevel approach to predicting community addiction treatment attitudes about
      contingency management.
AB  - Adoption of contingency management (CM) by the addiction treatment community is
      limited to date despite much evidence for its efficacy. This study examined
      systemic and idiographic staff predictors of CM adoption attitudes via archival
      data collected from treatment organizations affiliated with the National Drug
      Abuse Treatment Clinical Trials Network. Multilevel modeling analyses evaluated
      potential predictors from organizational, treatment unit, and workforce surveys.
      Among these were individual and shared perceptions of staff concerning aspects of
      their clinic culture and climate. Modeling analyses identified three systemic
      predictors (clinic provision of opiate agonist services, national accreditation,
      and lesser shared perception of workplace stress) and five idiographic predictors
      (staff with a graduate degree, longer service tenure, managerial position, e
      communication facility, and openness to change in clinical procedures). Findings
      are discussed as they relate to extant literature on CM attitudes and established
      implementation science constructs, and their practical implications are
      discussed.

PMID- 22138200
TI  - An intervention to increase alcohol treatment engagement: a pilot trial.
AB  - OBJECTIVES: Previous research has documented the difficulty individuals with
      alcohol use disorders have initiating alcohol treatment. This study assessed the
      feasibility of a brief, cognitive-behavioral intervention designed to increase
      treatment initiation among individuals with alcohol use disorders. METHODS: This
      randomized controlled trial included 196 participants who screened positive for a
      possible alcohol use disorder on the alcohol use disorders identification test.
      Randomly assigned intervention participants were administered a brief cognitive
      behaviorally-based intervention by telephone designed to modify beliefs that may
      interfere with treatment-seeking behavior. Beliefs about treatment and treatment
      seeking behavior were assessed postintervention. RESULTS: Participants receiving
      the intervention had significantly improved their attitudes toward addiction
      treatment (p < .002) and increased their reported intention-to-seek treatment (p
      < .000) postintervention. Further, intervention participants were almost three
      times more likely to attend treatment within a 3-month period (odds ratio = 2.60,
      p < .025) than participants in the control group. CONCLUSIONS: A brief, cognitive
      behavioral intervention delivered by telephone and focused on modifying treatment
      interfering beliefs holds promise for increasing alcohol treatment seeking among
      individuals in need.

PMID- 22138201
TI  - Assessing self-determined motivation for addiction treatment: validity of the
      Treatment Entry Questionnaire.
AB  - Although legal, formal, and informal social controls are frequently used to
      pressure individuals to enter treatment, motivational consequences of using these
      tactics have been neglected. Self-determination theory (SDT) provides a useful
      perspective for understanding client experiences of social controls and
      highlights the importance of self-determined motivation for long-term behavior
      change. This study assessed the construct validity of the Treatment Entry
      Questionnaire (TEQ), a brief scale derived from SDT to measure identified,
      introjected, and external treatment motivation. Two independent samples of
      clients entering Canadian residential and outpatient treatment completed TEQ
      items (ns = 529 and 623). Exploratory and confirmatory factor analyses supported
      a 9-item version of the scale, with 3 factors aligning with SDT motivational
      subtypes. Subscales showed high internal consistency and correlated as expected
      with social controls and perceived coercion at treatment entry. The TEQ-9 is a
      valid option for assessing self-determined motivation in clinical practice and
      evaluating coerced addiction treatment.

PMID- 22138204
TI  - Morphology informed by phylogeny reveals unexpected patterns of species
      differentiation in the aquatic moss Rhynchostegium riparioides s.l.
AB  - Bryophyte floras typically exhibit extremely low levels of endemism. The
      interpretation, that this might reflect taxonomic shortcomings, is tested here
      for the Macaronesian flora, using the moss species complex of Rhynchostegium
      riparioides as a model. The deep polyphyly of R. riparioides across its
      distribution range reveals active differentiation that better corresponds to
      geographic than morphological differences. Morphometric analyses are, in fact,
      blurred by a size gradient that accounts for 80% of the variation observed among
      gametophytic traits. The lack of endemic diversification observed in R.
      riparioides in Macaronesia weakens the idea that the low rates of endemism
      observed in the Macaronesian bryophyte flora might solely be explained by
      taxonomic shortcomings. To the reverse, the striking polyphyly of North American
      and European lineages of R. riparioides suggests that the similarity between the
      floras of these continents has been over-emphasized. Discriminant analyses point
      to the existence of morphological discontinuities among the lineages resolved by
      the molecular phylogeny. The global rate of error associated to species
      identification based on morphology (0.23) indicates, however, that intergradation
      of shape and size characters among species in the group challenges their
      identification.

PMID- 22138203
TI  - [Therapeutic compliance in patients with arterial hypertension and type 2
      diabetes mellitus].
AB  - OBJECTIVE: 1) To determine gender differences regarding therapeutic adherence in
      patients with arterial hypertension and type 2 diabetes mellitus. 2) To detect
      differences in terms of age. 3) To determine existing relationships in patient
      compliance levels between Morisky-Green's test, Batalla's test and the pill count
      expressed as a percentage of compliance. METHOD: Descriptive, transversal study,
      carried out for a period of 7 months in the Primary Health Care, Health Centre in
      Renteria-Beraun (Guipuzcoa), Basque Health Service (Osakidetza), with an
      incidental sample of 100 patients diagnosed with hypertension and type 2 diabetes
      mellitus and receiving oral treatment. Principal variables: age, gender.
      Conditioning variables: years of evolution of each pathology, number of
      prescribed medicines, time lapse of prescription collection, Morisky-Green's
      test, Batalla's test and pill count. RESULTS: The statistical analysis yielded
      similar compliance for men and women, and for different age groups (Morisky-Green
      and pill count). Approximately 50% of the patients had adequate compliance
      according to at least one of the 3 tests. A greater relationship was found
      between Morisky-Green's test and the pill count method, and medication adherence
      improved when knowledge of the disease increased, and when the number of
      prescribed pills became smaller. CONCLUSIONS: Adherence varies according to the
      evaluation tool used, non-adherence is high and knowledge of the disease helps
      compliance. This suggests the convenience of systematically reviewing treatments
      and supplying more information to patients.

PMID- 22138202
TI  - Impact of a training and certification program on the quality of interviewer
      collected self-report assessment data.
AB  - The purpose of this study was to evaluate the impact of an assessment training
      and certification program on the quality of data collected from clients entering
      substance abuse treatment. Data were obtained from 15,858 adult and adolescent
      clients entering 122 treatment sites across the United States using the Global
      Appraisal of Individual Needs-Initial (GAIN-I). GAIN Administration and Fidelity
      Index (GAFI) scores were predicted from interviewer certification status,
      interviewer experience, and their interactions. We controlled for client
      characteristics expected to lengthen or otherwise complicate interviews. Initial
      bivariate analyses revealed effects for certification status and experience. A
      significant interaction between certification and experience indicates
      interviewers attaining certification and having more experience far outperformed
      certified interviewers with low experience. Although some client characteristics
      negatively impacted fidelity, interviewer certification and experience remained
      salient predictors of fidelity in the multivariate model. The results are
      discussed with regard to the importance of ongoing monitoring of interviewer
      skill.

PMID- 22138205
TI  - Optimizing the utility of high-resolution computed tomography in diagnosing
      exogenous lipoid pneumonia.

PMID- 22138207
TI  - A steroid isolated from the water mold Achlya heterosexualis induces neurogenesis
      in vitro and in vivo.
AB  - Using 22R-hydroxycholesterol as a sub-structure to screen natural compound
      databases, we identified a naturally occurring steroid (sc-7) with a 16-acetoxy
      22R-hydroxycholesterol moiety, in which the hydroxyl groups in positions 3 and 22
      are esterified by an acetoxy group and in which the carbon in position 26 carries
      a functional diacetylamino. sc-7 is an analog of the sex steroids dehydro
      oogoniol and antheridiol, can be isolated from the water mold Achlya
      heterosexualis, and promoted neurogenesis in vitro and in vivo. Mouse embryonic
      teratocarcinoma P19 cells exposed to sc-7 for 2days followed by a 5-day wash-out
      differentiated into cholinergic neurons that expressed specific neuronal markers
      and displayed axonal formation. Axons continued growing up to 28days after
      treatment. In vivo, infusion of sc-7 for 2weeks into the left ventricle of the
      rat brain followed by a 3-week wash-out induced bromodeoxyuridine uptake by cells
      of the ependymal layer and subventricular zone that co-localized with
      doublecortin and glial fibrillary acidic protein immunostaining, demonstrating
      induction of proliferation and differentiation of neuronal progenitors. Migrating
      neuroblasts were also observed in the corpus callosum. Thus, under these
      experimental conditions, adult ependymal cells resumed proliferation and
      differentiation. Taken together, these results suggest that sc-7 is an
      interesting molecule for stimulating in situ neurogenesis from resident neuronal
      progenitors as part of neuron replacement therapy. sc-7 did not bind to nuclear
      steroid receptors and was not metabolized as a steroid, supporting our hypothesis
      that the neurogenic effect of sc-7 is not likely due to a steroid-like effect.

PMID- 22138208
TI  - Interplay of estrogen receptors and GPR30 for the regulation of early membrane
      initiated transcriptional effects: A pharmacological approach.
AB  - Estrogens exert their effect through ERalpha and ERbeta intracellular
      transcription factors and rapid, usually membrane-initiated receptors,
      influencing cytosolic signaling and transcription. The nature of extranuclear
      estrogen elements has not been elucidated so far; classical or alternatively
      transcribed ER isoforms (ERalpha36, ERalpha46) anchored to the plasma membrane
      and GPR30 (GPER1) have been reported to exert early estrogen actions. Here, we
      used E2-BSA, an impermeable estradiol analog for a transcriptome analysis in four
      GREP1 positive breast cancer cell lines with different estrogen receptor profiles
      (T47D, MCF-7, MDA-MB-231 and SKBR3) in order to evaluate GPER1 transcriptional
      effects. Early effects of E2-BSA were assayed after 3h of incubation, in the
      absence/presence of ICI182,780 (ER-inhibitor) or G15 (GREP1-specific inhibitor).
      E2-BSA specifically modified 277-549 transcripts in the different cell lines. Two
      different clusters of transcripts could be identified: (1) the majority of
      transcripts were inhibited by both ICI182,780 and G15, suggesting an interaction
      of E2-BSA with a common ER-related element, or a direct ER-GPER1 interaction; (2)
      a small number of G15-only modified transcripts, in two cell lines (T47D and
      SKBR3 cells), indicative of specific GPER1-related effects. The latter
      transcripts were significantly related to pathways including FOXA2/FOXA3
      transcription factor networks, RNA-Polymerases Transcription Regulation and lipid
      metabolism, while ICI/G15 inhibited transcripts affected pathways related to
      apoptosis, erythropoietin signaling, metabolic effects through the citric acid
      cycle, IL-4 and IL-5 mediated events and homologous DNA recombination. Finally,
      we review the current literature of GPER1 actions, in view of our results of ER
      dependent and independent GPER1-modified pathways.

PMID- 22138209
TI  - Commentary on "Renal vein stenting via the right internal jugular vein approach
      with a provocative Valsalva maneuver to reduce the risk of stent migration".

PMID- 22138206
TI  - Respiratory impairment and the aging lung: a novel paradigm for assessing
      pulmonary function.
AB  - BACKGROUND: Older persons have an increased risk of developing respiratory
      impairment because the aging lung is likely to have experienced exposures to
      environmental toxins as well as reductions in physiological capacity. METHODS:
      Systematic review of risk factors and measures of pulmonary function that are
      most often considered when defining respiratory impairment in aging populations.
      RESULTS: Across the adult life span, there are frequent exposures to
      environmental toxins, including tobacco smoke, respiratory infections, air
      pollution, and occupational dusts. Concurrently, there are reductions in
      physiological capacity that may adversely affect ventilatory control, respiratory
      muscle strength, respiratory mechanics, and gas exchange. Recent work has
      provided a strong rationale for defining respiratory impairment as an age
      adjusted reduction in spirometric measures of pulmonary function that are
      independently associated with adverse health outcomes. Specifically, establishing
      respiratory impairment based on spirometric Z-scores has been shown to be
      strongly associated with respiratory symptoms, frailty, and mortality.
      Alternatively, respiratory impairment may be defined by the peak expiratory flow,
      as measured by a peak flow meter. The peak expiratory flow, when expressed as a Z
      score, has been shown to be strongly associated with disability and mortality.
      However, because it has a reduced diagnostic accuracy, peak expiratory flow
      should only define respiratory impairment when spirometry is not readily
      available or an older person cannot adequately perform spirometry. CONCLUSIONS:
      Aging is associated with an increased risk of developing respiratory impairment,
      which is best defined by spirometric Z-scores. Alternatively, in selected cases,
      respiratory impairment may be defined by peak expiratory flow, also expressed as
      a Z-score.

PMID- 22138210
TI  - Immunogenicity, safety and tolerability of MF59-adjuvanted seasonal influenza
      vaccine in children with juvenile idiopathic arthritis.
AB  - In order to evaluate the immunogenicity, safety, and tolerability of the MF-59
      adjuvanted seasonal influenza vaccine in children and adolescents with juvenile
      idiopathic arthritis (JIA) treated with different anti-rheumatic drugs, 60
      pediatric patients with JIA (30 treated with disease-modifying anti-rheumatic
      drugs [DMARDs] and 30 with etanercept) were compared with 30 healthy controls of
      similar gender and age. All of the patients received a single dose of the MF59
      adjuvanted seasonal influenza vaccine (Fluad, Siena, Italy). Immunogenicity was
      assessed at baseline, and 1 and 3 months post-vaccination; safety and
      tolerability were also evaluated during the study period. The JIA patients
      treated with etanercept showed significantly lower geometric mean titres (GMTs)
      against the A/H1N1 strain than those treated with DMARDs (p<0.05) and the healthy
      controls (p<0.05), who had similar GMTs. The etanercept-treated JIA patients also
      showed a significant reduction in GMTs against the A/H1N1 and A/H3N2 strains from
      1 to 3 months after vaccination (p<0.05). Furthermore, their seroconversion and
      seroprotection rates, and B antigen GMTs, were all significantly lower than those
      of the subjects in the other two groups (p<0.05). The safety and tolerability of
      the vaccine were good and similar between the groups. The results of this study
      indicate a reduced immune response to MF59-adjuvanted seasonal influenza vaccine
      in JIA children and adolescents treated with etanercept in comparison with those
      treated with DMARDs and healthy controls. The safety and tolerability of the
      vaccine appeared to be good in all of the study population.

PMID- 22138211
TI  - Phase I study of a Neisseria meningitidis liposomal vaccine containing purified
      outer membrane proteins and detoxified lipooligosaccharide.
AB  - Purified outer membrane proteins and purified deacylated lipooligosaccharide
      (dLOS) were formulated for use as a vaccine in three formulations for clinical
      use. The three vaccine formulations included (1) purified outer membrane proteins
      (OMPs) and L8-5 dLOS adsorbed to aluminum hydroxide; (2) purified OMPs and L8-5
      dLOS incorporated into liposomes; and (3) purified OMPs and L7 dLOS incorporated
      into proteoliposomes. The vaccines were compared for immunogenicity and safety in
      a phase 1clinical study. Ten adult volunteers were vaccinated with each of the
      three vaccine formulations. Two 50 MUg doses were given six weeks apart, and
      serum samples were obtained at 0, 2, 6, 8 and 14 weeks. Volunteers were evaluated
      for reactogenicity 30 min after vaccination and at days 1, 2, and 14 after each
      vaccination, and laboratory safety tests were done at 0, 2 and 6 weeks. Overall,
      the vaccines were well tolerated. Bactericidal assays against a homologous strain
      showed a four-fold or greater increase in titer in 6 of 7 volunteers in group
      one, 9 of 10 volunteers in group two, and 5 of 10 volunteers in group three. A
      quantitative enzyme linked immunosorbant assay showed increases in antibody
      against both OMPs and LOS antigens. The liposome formulation appeared to be
      particularly effective in presenting the dLOS as an antigen.

PMID- 22138212
TI  - Influenza vaccine effectiveness among adult patients in a University of Lyon
      hospital (2004-2009).
AB  - The aim of this study was to estimate influenza vaccine effectiveness (IVE)
      against laboratory-confirmed influenza among hospitalized patients. A case
      control investigation was based on the prospective surveillance of influenza-like
      illness (ILI) during five flu seasons. We compared influenza-positive cases and
      influenza-negative controls. Unadjusted overall IVE was 62% (95% confidence
      interval 24% to 81%). We found that IVE was lower during the 2004-05 flu season
      (11%; 95% CI -232% to 76%) when the vaccine and circulating viruses were
      mismatched. Expansion of the study to other hospitals could provide IVE estimates
      earlier in the season, for different age groups and emerging virus strains.

PMID- 22138213
TI  - Body knowledge in brain-damaged children: a double-dissociation in self and
      other's body processing.
AB  - Bodies are important element for self-recognition. In this respect, in adults it
      has been recently shown a self vs other advantage when small parts of the
      subjects' body are visible. This advantage is lost following a right brain lesion
      underlying a role of the right hemisphere in self body-parts processing. In order
      to investigate the bodily-self processing in children and the development of its
      neuronal bases, 57 typically developing healthy subjects and 17 subjects with
      unilateral brain damage (5 right and 12 left sided), aged 4-17 years, were
      submitted to a matching-to-sample task. In this task, three stimuli vertically
      aligned were simultaneously presented at the centre of the computer screen.
      Subjects were required which of two stimuli (the upper or the lower one) matched
      the central target stimulus, half stimuli representing self and half stimuli
      representing other people's body-parts and face-parts. The results showed that
      corporeal self recognition is present since at least 4 years of age and that self
      and others' body parts processing are different and sustained by separate
      cerebral substrates. Indeed, a double dissociation was found: right brain damaged
      patients were impaired in self but not in other people's body parts, showing a
      self-disadvantage, whereas left brain damaged patients were impaired in others'
      but not in self body parts processing. Finally, since the double dissociation
      self/other was found for body-parts but not for face parts, the corporal self
      seems to be dissociated for body and face-parts. This opens the possibility of
      independent and lateralized functional modules for the processing of self and
      other body parts during development.

PMID- 22138214
TI  - Population structure of a novel putative mycovirus infecting the conifer root-rot
      fungus Heterobasidion annosum sensu lato.
AB  - We describe a novel putative mycovirus infecting the conifer root-rot fungus
      Heterobasidion annosum sensu lato. This virus, designated as Heterobasidion RNA
      virus 6 (HetRV6), is taxonomically distant from all previously known viruses of
      Heterobasidion species, but somewhat related to the Curvularia thermal tolerance
      virus and the Fusarium graminearum virus 4. Based on a population analysis
      including 35 virus strains from Heterobasidion abietinum, Heterobasidion
      parviporum, Heterobasidion annosum sensu stricto and Heterobasidion occidentale,
      HetRV6 showed a considerable degree of geographical and host-related
      differentiation. The North American and Eurasian virus populations were clearly
      separated. In Eurasia, we observed cases of discrepancy between virus and host
      taxonomy, suggesting interspecies virus transfer. HetRV6 was also successfully
      transmitted between the three European species H. abietinum, H. annosum and H.
      parviporum. Based on growth rate tests on agar plates and spruce stem pieces,
      HetRV6 seemed to be cryptic or slightly mutualistic to its host.

PMID- 22138215
TI  - Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway.
AB  - The molecular mechanisms of assembly and budding of hepatitis C virus (HCV)
      remain poorly understood. The budding of several enveloped viruses requires an
      endosomal sorting complex required for transport (ESCRT), which is part of the
      cellular machinery used to form multivesicular bodies (MVBs). Here, we
      demonstrated that Hrs, an ESCRT-0 component, is critical for the budding of HCV
      through the exosomal secretion pathway. Hrs depletion caused reduced exosome
      production, which paralleled with the decrease of HCV replication in the host
      cell, and that in the culture supernatant. Sucrose-density gradient separation of
      the culture supernatant of HCV-infected cells revealed the co-existence of HCV
      core proteins and the exosome marker. Furthermore, both the core protein and an
      envelope protein of HCV were detected in the intraluminal vesicles of MVBs. These
      results suggested that HCV secretion from host cells requires Hrs-dependent
      exosomal pathway in which the viral assembly is also involved.

PMID- 22138216
TI  - A de novo 3.57 Mb microdeletion in 8q12.3q13.2 in a patient with mild
      intellectual disability and epilepsy.
AB  - A female patient, nine years of age, is reported with a history characterized by
      delay of psychomotor and speech development, mild to moderate intellectual
      disability and persistent sleep disturbances since the age of two. The patient
      showed facial dysmorphisms, a pectus excavatum and a sandal gap. Apart from
      lowered intelligence, neuropsychological functioning disclosed impaired
      attentional capacities and executive control as well as weak motor skills. Genome
      wide SNP array analysis revealed a 3.57 Mb de novo microdeletion in band q12.3 of
      chromosome 8. The long lasting sleep disorders turned out to originate from a
      rare juvenile epilepsy, continuous spike-waves during slow sleep (CSWS) syndrome,
      that includes the electrical status epilepticus in sleep (ESES) phenomenon. MRI
      scanning of the brain showed no abnormalities. To the authors knowledge, this is
      the first report of a de novo 8q12.3q13.2 microdeletion syndrome that presents
      with ESES/CSWS.

PMID- 22138217
TI  - Endocrine and anatomical findings in a case of Solitary Median Maxillary Central
      Incisor Syndrome.
AB  - Solitary Median Maxillary Central Incisor Syndrome (SMMCI) is a rare malformation
      syndrome consisting of multiple, mainly midline defects. Some authors suggest
      that it is a mild manifestation of the wide spectrum of holoprosencephaly, others
      classify it rather as a distinct entity. Authors report a case of SMMCI
      presenting with growth retardation, mild intellectual disability and absence of
      puberty. Cytogenetic and molecular cytogenetic investigations could identify no
      abnormalities. The presence of a single maxillary incisor called for further
      investigations to clarify hidden anomalies, these were empty sella,
      panhypopituitarism, hypothyroidism, and hypoplasia of the inner genitals. Based
      on the above findings, growth hormone, estrogen, and L-thyroxine substitution was
      introduced, which resulted in satisfactory longitudinal growth and onset of
      sexual maturation. We suggest genetic counselling and if needed, invasive
      investigations in female patients with short stature and absent/delayed puberty,
      with or without sex chromosomal anomalies, as the adequate therapy and even the
      quality of life of patient depends largely on the knowledge of their anatomical
      and endocrine status.

PMID- 22138218
TI  - LPS-induced TNFalpha factor (LITAF) in the snail Cipangopaludina chinensis: gene
      cloning and its apoptotic effect on NCI-H446 cells.
AB  - LPS-induced TNFalpha factor (LITAF) is a transcription factor mediating TNF-alpha
      expression under LPS stimulation, and playing important roles in immune
      responses. In the present study, partial cDNA sequence of a LITAF (designated
      CcLITAF) gene was cloned and identified from snail Cipangopaludina chinensis. It
      contains an open reading frame of 348 nucleotides encoding a predicted protein of
      115 amino acids, with a conserved LITAF domain at C-terminal, and shares a
      similarity ranging from 34% to 96% with other LITAF from oyster to mammals.
      CcLITAF mRNA ubiquitously expressed in all analyzed tissues. Interestingly,
      cLITAF could induce apoptosis in human tumor cell line, NCI-H446 cells, and
      caspase 3 play key roles in CcLITAF-mediated apoptosis. Present studies provide
      new insight into the biological function of CcLITAF.

PMID- 22138219
TI  - Modulation of neuroplastic changes and corticotropin-releasing factor-associated
      behavior by a phylogenetically ancient and conserved peptide family.
AB  - The co-evolution of peptides and early cells some 3.7 billion years ago provided
      bioactive peptides with a long history for the proliferation and refinement of
      peptide hormones. Central to the adaptation and evolution of cell types in
      metazoans is the development of peptide signaling systems that regulate stress
      mechanisms. The corticotropin-releasing factor (CRF) family of peptides
      represents the canonical family of peptides that are pivotal to the regulation of
      stress in vertebrates. However, these peptides appear to have evolved at least 2
      billion years after the formation of the first postulated bioactive peptides,
      suggesting that before this, other peptide systems played a role in stress and
      energy metabolism. The teneurin C-terminal associated peptides (TCAPs) are a
      recently discovered family of highly conserved peptides that are processed from
      the teneurin transmembrane proteins. This peptide/protein system is ubiquitous in
      multicellular organisms and evolved before the CRF family. TCAP-1 is a potent
      regulator of CRF-associated physiology and behavior and may play a significant
      role in the regulation of cell-to-cell communication and neuroplasticity in
      neurons.

PMID- 22138221
TI  - Estrogen regulation of brain vasotocin secretion in the catfish Heteropneustes
      fossilis: an interaction with catecholaminergic system.
AB  - Vasotocin (VT) is a basic neurohypophysial nonapeptide in non-mammalian
      vertebrates and is involved in diverse functions like osmoregulation,
      reproduction, metabolism and behavior. In this study, we report that estradiol
      17beta (E(2)) regulates brain and plasma VT secretion through the involvement of
      the catecholaminergic (CA) system. To demonstrate this, E(2) level was altered
      through ovariectomy (OVX, 3 weeks) and replacement study with low and high E(2)
      doses (0.1 and 0.5 MUg/g body weight). CA activity was inhibited by treatment
      with alpha-methylparatyrosine (alpha-MPT; 250 MUg/g body weight), a competitive
      inhibitor of tyrosine hydroxylase. VT was assayed by an enzyme immunoassay
      method. In the sham group, the low E(2) dose produced 82% and 104% increase,
      respectively, in brain and plasma VT levels. The high E(2) dose decreased the VT
      levels significantly. The low E(2) dose decreased brain E(2) but elevated plasma
      E(2). In the high E(2) group, the E(2) level increased further in both brain and
      plasma. OVX resulted in a significant inhibition (69% and 25%, respectively) of
      both brain and plasma VT, which was correlated with low E(2) levels. The low E(2)
      dose not only reversed the inhibition, but increased the VT level in both brain
      and plasma in comparison to the sham groups. The high E(2) replacement inhibited
      VT levels further low in both brain and plasma. The alpha-MPT treatment inhibited
      VT levels significantly in both sham and OVX groups. The drug treatment abolished
      partially the restorative effect of the low E(2) dose in the ovariectomized fish.
      In the high E(2) dose group, alpha-MPT decreased brain and plasma VT levels
      further low compared to the sham + 0. 5 MUg E(2) group or OVX + 0.5 MUg E(2)
      group except the brain VT level, which increased in the OVX+0.5 MUg E(2) group.
      It is inferred that E(2) may exert biphasic effects on VT through the mediation
      of the CA system.

PMID- 22138220
TI  - 7alpha-Hydroxypregnenolone, a new key regulator of amphibian locomotion:
      discovery, progress and prospect.
AB  - Seasonally-breeding amphibians have served as excellent animal models to
      investigate the biosynthesis and biological actions of neurosteroids. Previous
      studies have demonstrated that the brain of amphibians possesses key
      steroidogenic enzymes and produces pregnenolone, a precursor of steroid hormones,
      and other various neurosteroids. We recently found that the brain of seasonally
      breeding newts actively produces 7alpha-hydroxypregnenolone, a previously
      undescribed amphibian neurosteroid. This novel amphibian neurosteroid acts as a
      neuronal modulator to stimulate locomotor activity in newts. Subsequently, the
      mode of action of 7alpha-hydroxypregnenolone has been demonstrated in the newt
      brain. 7alpha-Hydroxypregnenolone stimulates locomotor activity through
      activation of the dopaminergic system. To understand the functional significance
      of 7alpha-hydroxypregnenolone in the regulation of locomotor activity, diurnal
      and seasonal changes in synthesis of 7alpha-hydroxypregnenolone have also been
      demonstrated in the newt brain. Melatonin derived from the pineal gland and eyes
      regulates 7alpha-hydroxypregnenolone synthesis in the brain, thus inducing
      diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates
      7alpha-hydroxypregnenolone synthesis in the brain, and also induces seasonal
      locomotor changes. In addition, 7alpha-hydroxypregnenolone mediates
      corticosterone action to increase locomotor activity under stress. This review
      summarizes the discovery, progress and prospect of 7alpha-hydroxypregnenolone, a
      new key regulator of amphibian locomotion.

PMID- 22138222
TI  - (19)F-heptuloses as tools for the non-invasive imaging of GLUT2-expressing cells.
AB  - Suitable analogs of d-mannoheptulose are currently considered as possible tools
      for the non-invasive imaging of pancreatic islet insulin-producing cells. Here,
      we examined whether (19)F-heptuloses could be used for non-invasive imaging of
      GLUT2-expressing cells. After 20 min incubation, the uptake of (19)F-heptuloses
      (25 mM) by rat hepatocytes, as assessed by (19)F NMR spectroscopy, ranged from
      0.50 (1-deoxy-1-fluoro-d-mannoheptulose and 3-deoxy-3-fluoro-d-mannoheptulose) to
      0.25 (1,3-dideoxy-1,3-difluoro-d-mannoheptulose) and 0.13 (1-deoxy-1-fluoro-d
      glucoheptulose, 3-deoxy-3-fluoro-d-glucoheptulose and 1,3-dideoxy-1,3-difluoro-d
      glucoheptulose) MUmol per 3*10(6)cells. (19)F MRI experiments also allowed the
      detection of 1-deoxy-1-fluoro-d-mannoheptulose in rat hepatocytes. All three
      (19)F-mannoheptuloses cited above, as well as 7-deoxy-7-fluoro-d-mannoheptulose
      and 1-deoxy-1-fluoro-d-glucoheptulose inhibited insulin release evoked in rat
      isolated pancreatic islets by 10mM d-glucose to the same extent as that observed
      with an equivalent concentration (10mM) of d-mannoheptulose, while 3-deoxy-3
      fluoro-d-glucoheptulose and 1,3-dideoxy-1,3-difluoro-d-glucoheptulose (also 10mM)
      were less potent than d-mannoheptulose in inhibiting insulin release. The 1-deoxy
      1-fluoro-d-mannoheptulose and 3-deoxy-3-fluoro-d-mannoheptulose only marginally
      affected INS-1 cell viability. These findings are compatible with the view that
      selected (19)F-heptuloses may represent suitable tools for the non-invasive
      imaging of hepatocytes and insulin-producing cells by (19)F MRI.

PMID- 22138223
TI  - Upregulation of Polo-like kinase 2 gene expression by GATA-1 acetylation in human
      osteosarcoma MG-63 cells.
AB  - Polo-like kinase 2 (Plk2) is a member of the serine/threonine protein kinase
      family involved in cell-cycle regulation and cellular response to stresses. It is
      of great interest to investigate the molecular mechanisms that control the
      expression of Plk2. Here, using real-time PCR and Western blot assays, we show
      that trichostatin A (TSA), a histone deacetylase inhibitor, upregulated Plk2 mRNA
      and protein expression in the human osteosarcoma MG-63 cell line. Luciferase
      activity analysis of the truncated Plk2 promoter indicated that the region from 
      1220 to -830 of the Plk2 promoter was sensitive to TSA. Moreover, using the
      electrophoresis mobility shift assay and chromatin immunoprecipitation assay, we
      identified two GATA-1 responsive elements at positions -1051 and -949, to which
      GATA-1 binding was enhanced by TSA under in vitro and in vivo conditions.
      Immunoprecipitation and Western blot showed that the levels of acetylated GATA-1
      were increased with TSA in MG-63 cells, consistent with their binding affinities
      to the GATA-1 responsive elements. In summary, these data demonstrate that
      acetylation plays a crucial role in Plk2 expression and acetylation of GATA-1 by
      TSA treatment may upregulate their DNA-binding affinities, resulting in the
      activation of Plk2 promoter. These results may contribute to the understanding of
      the molecular mechanism of Plk2 regulation.

PMID- 22138224
TI  - Inhibition of MT1-MMP activity using functional antibody fragments selected
      against its hemopexin domain.
AB  - The membrane associated MMP, MT1-MMP, is a critical pericellular protease
      involved in tumour cell invasion and angiogenesis and is highly up-regulated in
      numerous human cancers. It therefore represents an exciting new therapeutic
      cancer-specific target. We have generated recombinant human scFv antibodies
      against the non-catalytic, hemopexin domain of MT1-MMP that modulate its
      interactions with collagen. One of these is an effective inhibitor of the
      invasive capacity of cancer cells and of angiogenesis in model systems. This
      demonstrates that targeting sites outside the catalytic domain presents a
      potential novel approach to proteinase inhibition that could have applications in
      cancer therapeutics.

PMID- 22138225
TI  - Increase in cell viability by polyamines through stimulation of the synthesis of
      ppGpp regulatory protein and omega protein of RNA polymerase in Escherichia coli.
AB  - It is known that polyamines increase cell growth through stimulation of the
      synthesis of several kinds of proteins encoded by the so-called "polyamine
      modulon". We recently reported that polyamines also increase cell viability at
      the stationary phase of cell growth through stimulation of the synthesis of
      ribosome modulation factor, a component of the polyamine modulon. Accordingly, we
      looked for other proteins involved in cell viability whose synthesis is
      stimulated by polyamines. It was found that the synthesis of ppGpp regulatory
      protein (SpoT) and omega protein of RNA polymerase (RpoZ) was stimulated by
      polyamines at the level of translation. Stimulation of the synthesis of SpoT and
      RpoZ by polyamines was due to an inefficient initiation codon UUG in spoT mRNA
      and an unusual location of a Shine-Dalgarno (SD) sequence in rpoZ mRNA.
      Accordingly, the spoT and rpoZ genes are components of the polyamine modulon
      involved in cell viability. Reduced cell viability caused by polyamine deficiency
      was prevented by modified spoT and rpoZ genes whose synthesis was not influenced
      by polyamines. Under these conditions, the level of ppGpp increased in parallel
      with increase of SpoT protein. The results indicate that polyamine stimulation of
      synthesis of SpoT and RpoZ plays important roles for cell viability through
      stimulation of ppGpp synthesis by SpoT and modulation of RNA synthesis by ppGpp
      RpoZ complex.

PMID- 22138226
TI  - Dissection of Drosophila MTF-1 reveals a domain for differential target gene
      activation upon copper overload vs. copper starvation.
AB  - Metal-responsive transcription factor-1 (MTF-1) is a zinc finger protein
      conserved from mammals to insects. It mediates protection against heavy metal
      load by activating the expression of metallothionein and other genes. In
      Drosophila, MTF-1 serves a dual function in that it not only helps to protect
      against heavy metal load but also induces the expression of Ctr1B, the gene for
      an intestinal copper importer, upon copper starvation. By dissecting Drosophila
      MTF-1 function, we have identified determinants for nuclear import and export,
      and characterized a phosphorylation site mutant (T127A) that differentially
      affects MTF-1 target genes. Further, by generating a series of fusion proteins
      with the heterologous DNA binding domain of Gal4 we identified a strong,
      constitutive activation domain in the central region of MTF-1 (aa 352-540). By
      contrast, an extended fusion protein that includes MTF-1's C-terminus (aa 352
      791) is not active in standard conditions but induced by copper load. The
      paramount regulatory importance of the C-terminal part, that harbors a cysteine
      rich "metallothionein-like" domain, was corroborated by different experiments.
      Transgenic flies expressing C-terminally truncated MTF-1 variants displayed high
      constitutive transcription of both, the genes for metallothioneins and the copper
      importer Ctr1B. The indiscriminate activation of these genes that are normally
      induced under opposite conditions of copper load and copper starvation manifested
      itself in a shortened lifespan, crippled wings, and female sterility.

PMID- 22138227
TI  - Monolithic molecular imprinted polymer fiber for recognition and solid phase
      microextraction of ephedrine and pseudoephedrine in biological samples prior to
      capillary electrophoresis analysis.
AB  - A novel capillary electrophoresis (CE) method coupled with monolithic molecular
      imprinted polymer (MIP) fiber based solid phase microextraction (SPME) was
      developed for selective and sensitive determination of ephedrine (E) and
      pseudoephedrine (PE). With in situ polymerization in a silica capillary mold and
      E as template, the MIP fibers could be produced in batch reproducibly and each
      fiber was available for 50 extraction cycles without significant decrease in
      extraction ability. Using the MIP fiber under optimized extraction conditions, CE
      detection limits of E and PE were greatly lowered from 0.20 to 0.00096 MUg/mL and
      0.12 to 0.0011 MUg/mL, respectively. Analysis of urine and serum samples by the
      MIP-SPME-CE method was also performed, with results indicating that E and PE
      could be selectively extracted. The recoveries and relative standard deviations
      (RSDs) for sample analysis were found in the range of 91-104% and 3.8-9.1%,
      respectively.

PMID- 22138228
TI  - Effect of socio-economic factors on delayed access to health care among Chinese
      cervical cancer patients with late rectal complications after radiotherapy.
AB  - OBJECTIVES: To determine the effect of socio-economic status (SES) on delayed
      access to medical treatment by Chinese cervical cancer patients who suffered from
      late rectal sequelae (LRS) after external beam radiation therapy (EBRT) and
      intracavitary brachytherapy. METHODS: Patients diagnosed with LRS were
      interviewed for their SES, factors including age, residing district, religion,
      marital status, income, education, insurance and patient delay (the time interval
      from the onset of symptoms to the first medical consultation) and other factors
      such as weight, symptom duration and disease stage at diagnosis. RESULTS: One
      hundred and twenty nine patients were interviewed. Seventy-one patients (55%)
      sought medical treatment within three months after the first symptom being
      recognized and fifty-eight patients (45%) delayed their medical treatment over 3
      months. The study shows that age >= 55 (OR=12.1; 95% CI: 3.3-43.9), lower
      education (OR=4.6; 95% CI: 2.0-10.4 for women with primary school education or
      illiterate), low annual household income (OR=2.3; 95% CI: 1.2-5.1) and
      widow/divorce (OR=0.1; 95% CI: 0.01-0.07) were the high risk factors for delayed
      reporting. Patients with bleeding or bleeding plus other symptoms (61.2%) were
      more likely to seek treatment within three months, compared to patients with
      other symptoms only (38.8%) (p=0.002). Additionally, delayed reporting was found
      to be significantly associated with the late stage of late rectal sequelae (LRS)
      (p=0.000) and the patients with 55 years or older (p=0.000). CONCLUSIONS: Delayed
      reporting and late-stage presentation of late rectal sequelae are more prevalent
      among Chinese cervical cancer patients with 55 years or older, low education,
      poor marital status, or poor financial status. Effective social support and
      educational programs should be implemented to encourage these patients to seek
      medical treatment as soon as possible.

PMID- 22138229
TI  - Predictive value of serum CA-125 levels in patients with persistent or recurrent
      epithelial ovarian cancer or peritoneal cancer treated with bevacizumab on a
      Gynecologic Oncology Group phase II trial.
AB  - OBJECTIVE: To compare two methods of determining therapeutic response and disease
      progression - modified Gynecologic Cancer Intergroup (GCIG) criteria based on CA
      125 and Radiographic Evaluation Criteria in Solid Tumors (RECIST), in a phase II
      trial of bevacizumab for patients with recurrent or persistent epithelial ovarian
      and peritoneal carcinoma. METHODS: Patients were treated with bevacizumab 15
      mg/kg every 21 days. Modified GCIG definitions of progression and response were
      retrospectively applied and compared to RECIST-defined progression and response.
      The prognostic significance of CA-125- and RECIST-defined responses and
      progressions were explored. RESULTS: Sixty-two patients were evaluable by RECIST,
      59 for progression by CA-125, and 45 for response by CA-125. Median progression
      free survival (PFS) by RECIST and progression-free interval (PFI) by CA-125 were
      4.7 and 5.2 months respectively. However, 12.9% of those with CA-125 defined
      progression remained progression-free according to RECIST for at least 8 months.
      Thirteen of 62 patients (21%) had response by RECIST and 14/45 (31%) by CA-125.
      Time dependent analyses indicated that progression by CA-125 was associated with
      a 5.2 fold increased risk of progression by RECIST, and response by CA-125 had a
      5 fold decrease in risk of progression by RECIST. Landmark and time dependent
      analyses showed prognostic value of responses by CA-125 and RECIST. CONCLUSIONS:
      In this study, disease assessment by RECIST and CA-125 appears to correlate in
      general. However, approximately 10% of patients might demonstrate progression
      earlier by CA-125.

PMID- 22138230
TI  - Disparities in hospice care among older women dying with ovarian cancer.
AB  - BACKGROUND: Timely hospice referral is an essential component of quality end-of
      life care, although a growing body of research suggests that for patients with
      various types of cancer, hospice referrals often occur very late in the course of
      care, and are marked by sociodemographic disparities. However, little is known
      about the ovarian cancer patient population specifically. We examined the extent
      and timing of hospice referrals in ovarian cancer patients over age 65, and the
      factors associated with these outcomes. METHODS: We used the Surveillance,
      Epidemiology, and End Results (SEER)-Medicare database to identify 8211 women
      aged 66+ with ovarian cancer who were diagnosed between 2001 and 2005 and died by
      December 31, 2007. We excluded women who were not eligible for Medicare A
      continuously during the 6 months prior to death. Outcomes studied included
      overall hospice use in the last 6 months of life and late hospice enrollment,
      defined as within 3 days of death. We examined variations in these two measures
      based on year of diagnosis and sociodemographic characteristics (age, race,
      marital status, rural residence, income, education) and type of Medicare received
      (fee-for-service vs. managed care). RESULTS: Among 8211 women in the cohort who
      died from ovarian cancer, 39.7% never received hospice care (3257/8211). Overall
      hospice care increased over the period of observation, from 49.7% in 2001 to
      63.6% [corrected] in 2005, but the proportion of women receiving hospice care
      within 3 days of death did not improve. Among those who received hospice care,
      11.2% (556/4954) and 26.2% (1299/4954) received such care within 3 and 7 days of
      death, respectively. A higher proportion of black women (46.5% vs. 38.4% among
      whites), women in the lowest income group (42.8% vs. 37.0% in the highest income
      group), and those receiving fee-for-service Medicare (41.3% vs.33.5% for women in
      managed care) never received hospice care. In multivariable models, factors
      associated with lack of hospice care included age younger than 80 years (OR 1.27,
      95% CI 1.15-1.40), non-white race (OR 1.44, 95% CI 1.26-1.65), low income (OR
      1.17, 95% CI 1.04-1.32) and enrollment in fee-for-service Medicare compared with
      managed care (OR 1.39, 95% CI 1.24-1.56). CONCLUSION: More older women with
      ovarian cancer are receiving hospice care over time, however, a substantial
      proportion receive such care very near death, and sociodemographic disparities in
      hospice care exist. Our data also support the need to target lower-income and
      minority women in efforts to increase optimally timed hospice referrals in this
      population. Our finding that ovarian cancer patients enrolled in managed care
      plans were more likely to receive hospice care suggests the importance of health
      care system factors in the utilization of hospice services.

PMID- 22138232
TI  - New approach illuminates how memory systems switch.
AB  - Whereas the classic view of systems consolidation involves an initial hippocampal
      dependent memory later giving way to neocortical structures, a recent study using
      precisely-timed optogenetic silencing of key brain areas reveals a more complex
      and dynamic interaction between systems competing for control over the expression
      of contextual fear memories.

PMID- 22138231
TI  - Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways.
AB  - Obsessive-compulsive disorder (OCD) affects approximately 2-3% of the population
      and is characterized by recurrent intrusive thoughts (obsessions) and repetitive
      behaviors or mental acts (compulsions), typically performed in response to
      obsessions or related anxiety. In the past few decades, the prevailing models of
      OCD pathophysiology have focused on cortico-striatal circuitry. More recent
      neuroimaging evidence, however, points to critical involvement of the lateral and
      medial orbitofrontal cortices, the dorsal anterior cingulate cortex and amygdalo
      cortical circuitry, in addition to cortico-striatal circuitry, in the
      pathophysiology of the disorder. In this review, we elaborate proposed features
      of OCD pathophysiology beyond the classic parallel cortico-striatal pathways and
      argue that this evidence suggests that fear extinction, in addition to behavioral
      inhibition, is impaired in OCD.

PMID- 22138233
TI  - Attention, the presolution period, and choice accuracy in pigeons.
AB  - Six pigeons were trained first on a color then on a form discrimination; four
      other pigeons were trained first on form and then on color. One of two colors or
      one of two forms (sample stimuli) appeared in the center of a touch sensitive
      monitor for 5 pigeons and in the center and in 16 other locations for 5 other
      pigeons. A peck anywhere within the region in which the sample stimuli appeared
      produced two white disks (comparison stimuli), one on the left and one on the
      lower right corners of the screen. Correct left-right choices provided food.
      Although of no consequence, the location of pecks in presence of the sample was
      predictive of the pigeon's subsequent choice. Accuracy, choice of the correct
      comparison stimulus, was greater when the sample stimuli appeared in the center
      as well as 16 other locations than when it appeared only in the center. The
      presolution period, the period of chance accuracy prior to evidence of
      discrimination learning, was decreased on each task following training on the
      other task. This evidence of facilitation following an extra-dimensional shift
      was attributed to continued relevance of the conditions under which the first
      task was learned. The duration of the presolution period was inversely related to
      asymptotic accuracy-data accounted for by Heinemann's (1983) theory of
      information processing during the presolution period.

PMID- 22138234
TI  - The accuracy of sentinel node biopsy in breast cancer patients with the history
      of previous surgical biopsy of the primary lesion: systematic review and meta
      analysis of the literature.
AB  - BACKGROUND: One of the subjects under debate in sentinel node mapping is the
      eligibility of patients with the history of previous surgical biopsy of the
      primary lesion for sentinel node biopsy. In the current systematic review, we
      evaluated the false negative and detection rates of sentinel node biopsy in
      breast cancer patients with and without previous surgical manipulation of the
      primary breast lesions. METHODS: Pubmed, SCOPUS, and Google scholar were searched
      for any relevant study with head to head comparison of patients with and without
      history of previous surgical manipulation of the primary breast lesions. The
      outcomes of interest were detection and false negative rates in each group, and
      odds ratio as well as risk difference of having sentinel node detection failure
      or getting false negative results in the surgical biopsy compared to the non
      surgical biopsy group. RESULTS: 18 studies for false negative rate and 68 studies
      for detection rate evaluation were included in this review. Pooled detection
      rates for patients with and without previous surgical biopsy were 91.3% and
      92.8%. Odds ratio and risk difference of having detection failure during surgery
      were 1.16 and 0.002 respectively. Pooled false negative rates for patients with
      and without previous surgical biopsy were 12.3% and 9.9%. Odds ratio and risk
      difference of having false negative results were 1.4 and 0.02 respectively.
      CONCLUSION: Surgical biopsy of the primary breast malignant lesions does not
      affect the detection rate of sentinel lymph node biopsy procedure. However, false
      negative rate seems to be slightly higher. We believe that the advantages of
      sentinel node biopsy outweigh this small difference.

PMID- 22138235
TI  - Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves
      insulin-mediated glucose transport signaling pathway in heart and ameliorates
      cardiac oxidative stress and apoptosis.
AB  - Hyperlipidemia, inflammation and altered antioxidant profiles are the usual
      complications in diabetes mellitus. In the present study, we investigated the
      therapeutic potential of taurine in diabetes associated cardiac complications
      using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of
      120mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally,
      in water) for three weeks either from the day of ALX exposure or after the onset
      of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes
      decreased body weight, increased glucose level, decreased insulin content,
      enhanced the levels of cardiac damage markers and altered lipid profile in the
      plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme
      activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid
      peroxidation, protein carbonylation and ROS generation) and enhanced the
      proinflammatory cytokines levels, activity of myeloperoxidase and nuclear
      translocation of NFkappaB in the cardiac tissue of the experimental animals.
      Taurine treatment could, however, result to a decrease in the elevated blood
      glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress,
      lipid profiles and NFkappaB translocation. In addition, taurine increased GLUT 4
      translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1
      at tyrosine and Akt at serine residue in the heart. Results also suggest that
      taurine could protect cardiac tissue from ALX induced apoptosis via the
      regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine
      supplementation in regular diet could play a beneficial role in regulating
      diabetes and its associated complications in the heart.

PMID- 22138236
TI  - Ethanol drinking-in-the-dark facilitates behavioral sensitization to ethanol in
      C57BL/6J, BALB/cByJ, but not in mu-opioid receptor deficient CXBK mice.
AB  - BACKGROUND: Neuroplasticity associated with drug-induced behavioral sensitization
      has been associated with excessive drug pursuit and consumption characteristic of
      addiction. Repeated intraperitoneal (ip) injections of ethanol (EtOH) can induce
      psychomotor sensitization in mice. In terms of its clinical relevance, however,
      it is important to determine whether this phenomenon can also be produced by
      voluntary EtOH consumption. METHODS: The present investigation used a drinking-in
      the-dark (DID) methodology to induce high levels of EtOH drinking in mice; EtOH
      replaces water for 2 or 4h, starting 3h after the beginning of the dark cycle.
      Animals followed a 3-week DID protocol prior to an evaluation of EtOH-induced
      locomotor activity (acute and repeated EtOH). For the first week, animals had
      access to 20% EtOH. On weeks 2 and 3, different concentrations of EtOH (10, 20 or
      30%) were used. Three different inbred strains of mice were used: C57BL/6J (B6),
      BALB/cByJ (BALB), and CXBK. The CXBK mouse line was used because of its reduced
      expression and functioning of brain mu-opioid receptors, which have been
      suggested to participate in the development of EtOH-induced sensitization. B6 and
      BALB mice were used as controls. RESULTS: B6 and CXBK mice presented comparable
      levels of EtOH drinking (approx. 3g/kg in 2h), that were higher than those showed
      by BALB. All animals, regardless of genotype, adjusted volume of EtOH intake to
      obtain stable g/kg of EtOH across concentrations. Previous EtOH DID produced (B6)
      or potentiated (BALB) sensitization to EtOH; this effect was not seen in CXBK.
      Western blot analysis showed a reduced number of mu-opioid receptors in several
      brain regions of CXBK as compared to that of B6 and BALB mice. CONCLUSIONS: In
      summary, here we show that the DID methodology can be used to trigger EtOH
      induced neuroplasticity supporting psychomotor sensitization, a process that
      might require participation of mu-opioid receptors.

PMID- 22138238
TI  - Flaviviral helicase: insights into the mechanism of action of a motor protein.
AB  - Motor proteins are involved in crucial cell activities, such as cargo transport
      or nucleic acid remodeling, by converting the free energy of ATP hydrolysis into
      motion or mechanical work. Flavivirus helicase is a motor protein involved in
      dsRNA separation during viral replication, thus essential for virus infection.
      Since a clear vision of the protein activity, in particular of the relationship
      between ATP cycling and dynamics, is missing, we carried over a molecular
      dynamics study on Dengue virus helicase in its ATP bound and unbound states. Our
      simulations show different opening levels of the ssRNA access site to the
      helicase core. Specifically, we show that ATP induces a closed state into the
      ssRNA access site, likely involved in the helicase unwinding activity.

PMID- 22138239
TI  - Prediction of pattern recognition receptor family using pseudo-amino acid
      composition.
AB  - Pattern recognition receptors (PRRs) play a key role in the innate immune
      response by recognizing pathogen associated molecular patterns derived from a
      diverse collection of microbial pathogens. PRRs form a superfamily of proteins
      related to host health and disease. Thus, prediction of PRR family might supply
      biologically significant information for functional annotation of PRRs and
      development of novel drugs. In this paper, a computational method is proposed for
      predicting the families of PRRs. The prediction was performed on the basis of
      amino acid composition and pseudo-amino acid composition (PseAAC) from primary
      sequences of proteins using support vector machines. A non-redundant dataset
      consisted of 332 PRRs in seven families was constructed to do training and
      testing. It was demonstrated that different families of PRRs were quite closely
      correlated with amino acid composition as well as PseAAC. In the jackknife test,
      overall accuracies of amino acid composition-based and PseAAC-based classifiers
      reached 96.1% and 97.9%, respectively. The results indicate that families of PRRs
      are predictable with high accuracy. It is anticipated that this computational
      method might be a powerful tool for the automated assignment of families of PRRs.

PMID- 22138240
TI  - High-active truncated luciferase of copepod Metridia longa.
AB  - The technology of real-time imaging in living cells is crucial for understanding
      of intracellular events. For this purpose, bioluminescent reporters have been
      introduced as sensitive and convenient tools. Metridia luciferase (MLuc) from the
      copepod Metridia longa is a coelenterazine-dependent luciferase containing a
      natural signal peptide for secretion. We report the high-active MLuc mutants with
      deletion of the N-terminal variable part of amino acid sequence. The MLuc
      variants were produced in Escherichia coli cells, converted to an active protein,
      and characterized. We demonstrate that the truncated MLucs have significantly
      increased bioluminescent activity as against the wild type enzyme but
      substantially retain other properties. One of the truncated variants of MLuc was
      transiently expressed in HEK 293 cells. The results clearly suggest that the
      truncated Metridia luciferase is well suited as a secreted reporter ensuring
      higher detection sensitivity in comparison with a wild type enzyme.

PMID- 22138237
TI  - Effect of nicotine on body composition in mice.
AB  - Nicotine induces weight loss in both humans and rodents consuming a regular diet;
      however, the effect of nicotine on body weight and fat composition in rodents
      consuming a high-fat diet (HFD) has not been well studied. Thus, this study
      examined the effect of nicotine vs saline on body weight and fat composition in
      mice fed with either an HFD (62% of kcal from fat) or a standard normal chow diet
      (NCD) for 7 weeks. Nicotine dose dependently reduced body weight gain in mice
      that consumed both diets, but this effect was significantly greater in mice on
      the HFD. Caloric intake was decreased in nicotine-treated mice. Estimates of
      energy intake suggested that decreased caloric intake accounted for all the
      reduced weight gain in mice on an NCD and 66% of the reduced weight gain on an
      HFD. Computed tomography analysis for fat distribution demonstrated that nicotine
      was effective in reducing abdominal fat in mice that consumed the HFD, with
      nicotine treatment leading to lower visceral fat. The effect of nicotine on
      weight loss in mice on an HFD was completely blocked by mecamylamine, a
      nonselective nicotinic acetylcholine receptor (nAChR) antagonist, but only
      partially blocked by the alpha4beta2 nAChR partial agonist/antagonist,
      varenicline. We conclude that nicotine is effective in preventing HFD-induced
      weight gain and abdominal fat accumulation.

PMID- 22138241
TI  - The iAbeta5p beta-breaker peptide regulates the Abeta(25-35) interaction with
      lipid bilayers through a cholesterol-mediated mechanism.
AB  - Alzheimer's disease is characterized by the deposition of aggregates of the beta
      amyloid peptide (Abeta) in the brain. A potential therapeutic strategy for
      Alzheimer's disease is the use of synthetic beta-sheet breaker peptides, which
      are capable of binding Abeta but unable to become part of a beta-sheet structure,
      thus inhibiting the peptide aggregation. Many studies suggest that membranes play
      a key role in the Abeta aggregation; consequently, it is strategic to investigate
      the interplay between beta-sheet breaker peptides and Abeta in the presence of
      lipid bilayers. In this work, we focused on the effect of the beta-sheet breaker
      peptide acetyl-LPFFD-amide, iAbeta5p, on the interaction of the Abeta(25-35)
      fragment with lipid membranes, studied by Electron Spin Resonance spectroscopy,
      using spin-labeled membrane components (either phospholipids or cholesterol). The
      ESR results show that iAbeta5p influences the Abeta(25-35) interaction with the
      bilayer through a cholesterol-mediated mechanism: iAbeta5p withholds cholesterol
      in the inner hydrophobic core of the bilayer, making the interfacial region more
      fluid and capable to accommodate Abeta(25-35). As a consequence, iAbeta5p
      prevents the Abeta(25-35) release from the lipid membrane, which is the first
      step of the beta-amyloid aggregation process.

PMID- 22138242
TI  - Adeno-associated virus Rep-mediated targeting of integrase-defective retroviral
      vector DNA circles into human chromosome 19.
AB  - Retroviral vectors have been employed in clinical trials for gene therapy owing
      to their relative large packaging capacity, alterable cell tropism, and
      chromosomal integration for stable transgene expression. However, uncontrollable
      integrations of transgenes are likely to cause safety issues, such as insertional
      mutagenesis. A targeted transgene integration system for retroviral vectors,
      therefore, is a straightforward way to address the insertional mutagenesis issue.
      Adeno-associated virus (AAV) is the only known virus capable of targeted
      integration in human cells. In the presence of AAV Rep proteins, plasmids
      possessing the p5 integration efficiency element (p5IEE) can be integrated into
      the AAV integration site (AAVS1) in the human genome. In this report, we describe
      a system that can target the circular DNA derived from non-integrating retroviral
      vectors to the AAVS1 site by utilizing the Rep/p5IEE integration mechanism. Our
      results showed that after G418 selection 30% of collected clones had retroviral
      DNA targeted at the AAVS1 site.

PMID- 22138243
TI  - Localization and force analysis at the single virus particle level using atomic
      force microscopy.
AB  - Atomic force microscopy (AFM) is a vital instrument in nanobiotechnology. In this
      study, we developed a method that enables AFM to simultaneously measure specific
      unbinding force and map the viral glycoprotein at the single virus particle
      level. The average diameter of virus particles from AFM images and the
      specificity between the viral surface antigen and antibody probe were integrated
      to design a three-stage method that sets the measuring area to a single virus
      particle before obtaining the force measurements, where the influenza virus was
      used as the object of measurements. Based on the purposed method and performed
      analysis, several findings can be derived from the results. The mean unbinding
      force of a single virus particle can be quantified, and no significant difference
      exists in this value among virus particles. Furthermore, the repeatability of the
      proposed method is demonstrated. The force mapping images reveal that the
      distributions of surface viral antigens recognized by antibody probe were
      dispersed on the whole surface of individual virus particles under the proposed
      method and experimental criteria; meanwhile, the binding probabilities are
      similar among particles. This approach can be easily applied to most AFM systems
      without specific components or configurations. These results help understand the
      force-based analysis at the single virus particle level, and therefore, can
      reinforce the capability of AFM to investigate a specific type of viral surface
      protein and its distributions.

PMID- 22138244
TI  - A novel role of miR-302/367 in reprogramming.
AB  - Ever since the technique of coaxing ordinary skin cells into becoming pluripotent
      stem cells (iPSCs) has been developed, which have the potential to become any
      cell or tissue in the body, efforts were made to improve the approach because
      some major challenges. Increasing evidence suggests that several microRNAs
      (miRNAs) are involved in early embryonic development and embryonic stem cell
      formation, known as embryonic stem cell (ESC)-specific miRNAs, particularly the
      miR-302 family. We summarized here a novel approach to generate iPSCs by using
      miR-302 and its related miRNAs such as miR-367. The development of this miR
      302/367-mediated iPSC (termed mirPSC) may provide tools to deal with the
      obstacles facing some current iPSC reprogramming methods. The mechanism by which
      miR-302/367 induce iPSC reprogramming is proposed.

PMID- 22138245
TI  - Heme oxygenase-1 (HO-1) is constitutively up-regulated in top alpinists.
AB  - Alpinists who challenge Mt. Everest need adaptation to hypoxia before the attack
      of Mt. Everest. Although this adaptation is important for the success of climbing
      Mt. Everest, the molecular mechanism on the adaptation to hypoxia is not well
      understood. In order to clarify this mechanism, we investigated hypoxia-induced
      gene expressions specific for top alpinists using microarray analyses. We report
      here that heme oxygenase-1 (HO-1) is significantly higher in the blood of top
      alpinist compared with non-alpinists. Although HO-1 expression of non-alpinists
      is also up-regulated in response to hypoxia, HO-1 level of the top alpinists are
      constitutively higher than that of non-alpinists. Serial examinations of HO-1 in
      one top alpinist revealed that the higher expression of HO-1 is maintained in
      high-level several months after the attack of top mountains. Taken together with
      the biochemical function of HO-1 that catalyzes heme into CO and bilirubin, HO-1
      expression may improve the circulation and compensate with oxidative tissue
      damages induced by hypoxia. These data also suggest that peripheral blood has the
      memory on hypoxia independent of antigens by maintaining the high-level of HO-1
      expression in top alpinists, which merits the rapid adaptation to hypoxia for
      8000m climbing.

PMID- 22138246
TI  - [Critical abdominal vascular impairment following binge eating].

PMID- 22138247
TI  - Effect of garlic sulfur compounds on neutrophil infiltration and damage to the
      intestinal mucosa by endotoxin in rats.
AB  - We investigated the protective effects of garlic sulfur compounds (GSCs),
      specifically, diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl
      trisulfide (DATS), on endotoxin-induced intestinal damage. Wistar rats received
      by gavage 0.125 or 0.025 mmol/kg body wt of each GSC or the vehicle (corn oil; 2
      mL/kg body wt) every other day for 2 weeks before being injected with endotoxin
      (ip, 5 mg/kg body wt). Control rats were administered corn oil and were injected
      with sterile saline. Rats were killed at 18 h after injection. Both doses of DAS
      suppressed endotoxin-induced neutrophilia, serum levels of sICAM-1 and CINC-1,
      cellular CD11b on neutrophils, and intestinal contents of ICAM-1, CINC-1, TNF
      alpha, and IL-1beta (p<0.05). DADS suppressed endotoxin-induced intestinal
      contents of ICAM-1, TNF-alpha, and IL-1beta at both doses, but only suppressed
      the serum sICAM-1 level and cellular CD11b on neutrophils at the low dose
      (p<0.05). DATS did not ameliorate the endotoxin-induced serum level of sICAM-1 or
      CINC-1 but suppressed intestinal IL-1beta at both doses. The low but not the high
      dose of DATS also ameliorated the intestinal contents of ICAM-1 and TNF-alpha
      (p<0.05). All GSCs reversed endotoxin-induced neutrophil infiltration and damage
      in the intestine, and the order of the effects of these GSCs to normalize
      intestinal morphology was DAS>DADS>DATS.

PMID- 22138248
TI  - Schizandrin prevents damage of murine mesangial cells via blocking NADPH oxidase
      induced ROS signaling in high glucose.
AB  - High glucose (HG) is the underlying factor contributing to long term complication
      of diabetes mellitus. Reactive oxygen species (ROS) have been postulated as a
      unifying mechanism for HG-induced complications. NADPH oxidase, producing
      superoxide anion, is the main source of ROS in diabetic nephropathy. In this
      study we report the inhibitory effect of schizandrin (Sch), an active ingredient
      of Fructus schisandrae, on HG-induced murine mesangial cells (MMCs) damage. Sch
      treatment significantly attenuated HG-induced proliferation and protein synthesis
      of MMCs in a dose dependent manner. The intracellular reactive oxygen species
      (ROS) level was also remarkably reduced by Sch as well as the enhanced NADPH
      oxidase activity, superoxide anion levels, NOX4 and p22phox protein expression,
      and phosphorylation of p47phox and p67phox. The phosphorylation level of mitogen
      activated kinase (MAPK) protein, phospho-Erk1/2 and -p38, and Akt was also
      significantly inhibited by Sch under HG condition. By using specific inhibitors,
      we found that Sch inhibits HG-induced mesangial cell proliferation and ECM
      overexpression via NADPH oxidase/PI3K-Akt-MAPK-dependent pathway in MMCs. Taken
      together; our demonstration of the ability of Sch to inhibit high glucose induced
      damage of MMCs has clinical implications in treatment of diabetic nephropathy.

PMID- 22138249
TI  - Garlic oil alleviated ethanol-induced fat accumulation via modulation of SREBP-1,
      PPAR-alpha, and CYP2E1.
AB  - Garlic oil (GO) has been shown to partially attenuate ethanol-induced fatty
      liver, but the underlying mechanisms remain unclear. The current study was
      designed to evaluate the protective effects of GO against ethanol-induced
      steatosis in vitro and in vivo, and to explore potential mechanisms by
      investigating the sterol regulatory element binding protein-1c (SREBP-1c),
      peroxisome proliferators-activated receptor-alpha (PPAR-alpha), cytochrome
      P4502E1 (CYP2E1), and etc. In the in vitro study, human normal cell LO2 was
      exposed to 100 mM ethanol in the presence or absence of GO for 24 h. We found
      that ethanol increased the protein levels of n-SREBP-1c and CYP2E1, but decreased
      the protein levels of PPAR-alpha, which was significantly attenuated by GO co
      treatment. In the in vivo study, male Kun-Ming mice were pretreated with single
      dose of GO (50-200 mg/kg body weight) at 2 h before ethanol (4.8 g/kg body
      weight) exposure. The changes of n-SREBP-1c, PPAR-alpha and CYP2E1 were
      paralleled well to those of in vitro study. Furthermore, GO significantly reduced
      the protein levels of fatty acid synthase (FAS), and suppressed ethanol-induced
      hepatic mitochondrial dysfunction. These results suggested that GO had the
      potential to ameliorate alcoholic steatosis which might be related to its
      modulation on SREBP-1c, PPAR-alpha, and CYP2E1.

PMID- 22138250
TI  - The unsuitability of split-thickness oral buccal mucosa tissue constructs to
      judge about the safety of ethanol-containing mouthrinses in vitro.

PMID- 22138251
TI  - Protective effects of xanthohumol against the genotoxicity of heterocyclic
      aromatic amines MeIQx and PhIP in bacteria and in human hepatoma (HepG2) cells.
AB  - Previous studies showed that xanthohumol (XN), a hop derived prenylflavonoid,
      very efficiently protects against genotoxicity and potential carcinogenicity of
      the food borne carcinogenic heterocyclic aromatic amine (HAA) 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ). In this study, we showed that XN was not
      mutagenic in Salmonella typhimurium TA98 and did not induce genomic instability
      in human hepatoma HepG2 cells. In the bacteria XN suppressed the formation of 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) induced mutations in a dose dependent
      manner and in HepG2 cells it completely prevented PhIP and MeIQx induced DNA
      strand breaks at nanomolar concentrations. With the QRT-PCR gene expression
      analysis of the main enzymes involved in the biotransformation of HAAs in HepG2
      cells we found that XN upregulates the expression of phase I (CYP1A1 and CYP1A2)
      and phase II (UGT1A1) enzymes. Further gene expression analysis in cells exposed
      to MeIQx and PhIP in combination with XN revealed that XN mediated up-regulation
      of UGT1A1 expression may be important mechanism of XN mediated protection against
      HAAs induced genotoxicity. Our findings confirm the evidence that XN displays
      strong chemopreventive effects against genotoxicity of HAAs, and provides
      additional mechanistic information to assess its potential chemopreventive
      efficiency in humans.

PMID- 22138252
TI  - Stimulatory effect on rat thymocytes proliferation and antimicrobial activity of
      two 6-(propan-2-yl)-4-methyl-morpholine-2,5-diones.
AB  - Recently we reported the identification and synthesis of cyclodidepsipeptides,
      3,6-di(propan-2-yl)-4-methyl-morpholine-2,5-dione (PPM) and 3-(2-methylpropyl)-6
      (propan-2-yl)-4-methyl-morpholine-2,5-dione (BPM), as potential precursors of
      enniatin B in Fusarium sporotrichioides. No data concerning biological activity
      of PPM and BPM have hitherto been published. The possible immunomodulatory effect
      and antimicrobial activity of PPM and BPM were investigated in this study, due to
      well known biological activities of enniatin B. The cytotoxicity effect of PPM
      and BPM on rat thymocytes demonstrated that increasing concentrations (0.1, 1, 10
      MUg/well) of PPM and BPM to cell culture, showed no significant effect on
      thymocytes toxicity. Simultaneously, incubation with studied cyclodidepsipeptides
      did not result with decreased mitochondrial membrane potential. Further,
      thymocytes exposure to increasing concentration of PPM and BPM was not able to
      induce significant reactive oxygen species (ROS) production in rat thymocytes.
      PPM and BPM administrations to cell culture in concentrations of 0.1 and 1
      MUg/well resulted with no significant increase of proliferative activity.
      However, significantly increased proliferative activity was detected with 10 MUg
      of PPM (p<0.001) and BPM (p<0.05), as compared to their respective controls. The
      in vitro antimicrobial activity of PPM and BPM was tested against two Gram
      positive and three Gram-negative bacteria. The results indicated that MIC values
      against tested strains ranged between 2.00 and 25.00 mg/ml. PPM showed much
      better activity against all tested bacteria in comparison with BPM. PPM was
      equally effective against both Gram-positive and Gram-negative bacteria, at the
      dose of 2.00 mg/ml.

PMID- 22138253
TI  - Mechanisms underlying muscle fatigue differ between multiple sclerosis patients
      and controls: a combined electrophysiological and neuroimaging study.
AB  - Increased sense of fatigue is an important and conspicuous symptom in multiple
      sclerosis (MS). Muscle fatigue is associated with increased sense of fatigue in
      MS (Steens et al., 2011). The aim of this study was to investigate mechanisms
      that can explain muscle fatigue in MS patients and controls. We assessed changes
      in cortical activation (BOLD), voluntary activation (twitch interpolation) and
      muscle force during a sustained maximal voluntary contraction (MVC) in twenty MS
      patients and twenty healthy controls. In control participants, individual
      differences in force decline (mean 65% MVC, 8 SD) during the sustained maximal
      contraction could be accounted for by differences in maximal voluntary force
      (R(2): 0.49, p = 0.001); stronger participants presented a larger force decline.
      The small decline in voluntary activation (mean 7.8%, 11.8 SD) did not contribute
      significantly to the force decline. During the sustained contraction, the force
      decline was accompanied by an increase in cortical activation in the main motor
      areas. In MS patients, the differences in the decline in force (mean 67% MVC, 9
      SD) were significantly associated (R(2): 0.51, p = 0.001) with a decline in
      voluntary activation (mean 20.1%, 20.6 SD) and not with maximal force or decline
      in rest twitch. The corresponding cortical activation in motor areas showed an
      increase in the first two intervals of the sustained contraction but declined
      during the last interval. Our data indicate that muscle fatigue during a
      sustained contraction in MS patients is associated with changes in the voluntary
      activation that are not sufficiently compensated by increased cortical
      activation. Control participants, however, show increased cortical activation to
      compensate for these fatigue-related changes in voluntary activation and the
      major cause of force decline is therefore to be found in the periphery (muscles).

PMID- 22138254
TI  - The effects of two microsporidian pathogens on the two-spotted lady beetle,
      Adalia bipunctata L. (Coleoptera: Coccinellidae).
AB  - Two-spotted lady beetles, Adalia bipunctata L. are available for biological pest
      control in North America. Lady beetles are known to host microsporidia and
      although these pathogens are able to infect more than one host under laboratory
      conditions, little is known regarding the effects of more than one microsporidian
      pathogen on host fitness. In this study, egg cannibalism was used to examine the
      effects of the microsporidium Tubulinosema hippodamiae from Hippodamia convergens
      and an undescribed microsporidium from A. bipunctata (alone and in combination)
      on A. bipunctata host fitness (larval development and mortality, sex ratio, adult
      fecundity and longevity). Development was prolonged significantly for larvae that
      were infected with the undescribed microsporidium but T. hippodamiae had no
      effect and as a result, conclusions could not be made regarding the effects of
      both pathogens on larval development. The two microsporidia had no effect on sex
      ratios (1?:1?) or on adult fecundity and longevity. Spores were detected in the
      majority of smear preparations of individuals that were fed microsporidia
      infected eggs and molecular analysis confirmed the identity of both pathogens in
      sampled individuals. T. hippodamiae spores were smaller than spores of the
      undescribed microsporidium (3.76+/-0.03*2.32+/-0.02 MUm and 5.43+/-0.06*2.75+/
      0.03 MUm, respectively) and although the former stained less intensely than did
      those of latter, spores of the two pathogens are difficult to differentiate when
      examined by light microscopy alone. The ability of some microsporidia to infect
      more than one lady beetle host makes it difficult to conclude with certainty as
      to the number of species that are present in infected Adalia when specimens are
      examined solely by light microscopy.

PMID- 22138255
TI  - Molecular detection of Spiroplasma apis and Spiroplasma melliferum in bees.
AB  - Spiroplasma apis and Spiroplasma melliferum are known as honey bee pathogens and
      are detected by unspecific methodologies like culturing or dark field microscopy.
      We developed a multiplex PCR being able to differentiate between both species and
      detect the genus Spiroplasma. This PCR can directly be used on culture samples or
      on DNA extracted bees. By PCR on cultured samples we were able to identify S.
      apis in Bombus pratorum and S. melliferum in Bombus pascuorum.

PMID- 22138256
TI  - Patient perspective on herpes zoster and its complications: an observational
      prospective study in patients aged over 50 years in general practice.
AB  - Understanding the effect of herpes zoster and zoster-related pain should inform
      care to improve health-related quality of life in elderly patients. A 12-month,
      longitudinal, prospective, multicenter observational study conducted in primary
      care in France enrolled patients aged >= 50 years with acute eruptive herpes
      zoster. Patient-reported zoster-related pain was assessed by validated
      questionnaires (Douleur Neuropathique en 4 Questions [DN4], Zoster Brief Pain
      Inventory [ZBPI], and Neuropathic Pain Symptom Inventory [NPSI]) on days 0 and
      15, and at months 1, 3, 6, 9, and 12. Health-related quality of life was assessed
      by the 12-item short-form health survey (SF-12) and the Hospital Anxiety and
      Depression scale on day 0 and at months 3, 6, and 12. Of 1358 patients included,
      1032 completed follow-up. Mean +/- standard deviation age was 67.7 +/- 10.7
      (range, 50-95) years; 62.2% were women. Most patients (94.1%) were prescribed
      antiviral drugs. The prevalence of zoster-related pain on day 0 and at months 3,
      6, 9, and 12 was 79.6%, 11.6%, 8.5%, 7.4%, and 6.0%, respectively. Patients with
      persistent pain had lower scores on the physical and mental component summaries
      of the SF-12 and the ZBPI interference score than those without pain. By logistic
      regression analysis, main predictive factors on day 0 for postherpetic neuralgia
      at month 3 were age, male sex, ZBPI interference score, Physical Component
      Summary score of the SF-12, and neuropathic quality of pain (DN4 score >= 4).
      Despite early diagnosis and treatment with antiviral agents, many patients with
      herpes zoster experience persistent pain and marked long-term reduction in health
      related quality of life.

PMID- 22138257
TI  - Proteinase 3 carries small unusual carbohydrates and associates with alphalpha
      defensins.
AB  - The neutrophil granulocyte is an important first line of defense against
      intruding pathogens and it contains a range of granules armed with antibacterial
      peptides and proteins. Proteinase 3 (PR3) is one among several serine proteases
      of the azurophilic granules in neutrophil granulocytes. Here, we characterize the
      glycosylation of PR3 and its association with antimicrobial human neutrophil
      peptides (HNPs, alpha-defensins) and the effect of these on the mechanism of
      inhibition of the major plasma inhibitor of PR3, alpha1-antitrypsin. The
      glycosylation of purified, mature PR3 showed some heterogeneity with
      carbohydrates at Asn 102 and 147 carrying unusual small moieties indicating heavy
      processing. Mass spectrometric analysis and immuno blotting revealed strong
      association of highly purified PR3 with alpha-defensins and oligomers hereof.
      Irreversible inhibition of PR3 by alpha1-antitrypsin did not affect its
      association with defensins. Other proteins from neutrophil granules were also
      found to be associated with defensins, whereas purified plasma proteins did not
      carry defensins. These results point to a role of defensins in controlling and
      targeting the activity of neutrophil granule proteins.

PMID- 22138259
TI  - Long term effect of low intensity pulsed ultrasound on a human tooth slice organ
      culture.
AB  - OBJECTIVE: Investigate the effect of therapeutic Low Intensity Pulsed Ultrasound
      (LIPUS) on human dentine-pulp complex in an in vitro model. DESIGN: 92 premolars
      were extracted from 23 adolescent orthodontic patients. The premolars were
      sectioned transversely into 600 MUm thick slices. The slices were divided into
      two main groups according to how often the LIPUS was applied (single or daily
      application), and then subdivided into five subgroups each (5, 10, 15 and 20 min
      and one control group). The tooth slices were cultured at (37  degrees C/5%
      CO(2)) in a humidified incubator where medium was changed every 48 h. LIPUS was
      applied using a 3.9 cm(2) transducer that produces an incident intensity of 30
      mW/cm(2). After five days, tissue was harvested for histomorphometrical analysis
      and real time PCR to investigate expression of genes of interest (Collagen I,
      DMP1, DSPP, TGF-beta1, RANKL and OPG). RESULTS: Histomorphometric analyses
      revealed that odontoblast cell count was higher in the single application groups
      (5, 10 and 15 min, respectively) than in the control and other treatment groups.
      Predentin thickness was higher in the single application group (10, 5 and 15 min)
      respectively than in the daily application group and the control groups, however
      they were not significantly different from each other. Real time PCR demonstrated
      no statistically significant difference between the groups in the expression of
      Collagen I, DMP1, TGF-beta1, DSPP, RANKL and OPG. CONCLUSION: Reproducible
      responses from cultured dentine-pulp complex were observed in groups with single
      application of LIPUS for 5, 10 and 15 min.

PMID- 22138258
TI  - Expressions of machismo in colorectal cancer screening among New Mexico Hispanic
      subpopulations.
AB  - Although national colorectal cancer (CRC) incidence rates have steadily
      decreased, the rate for New Mexico Hispanics has been increasing, and screening
      rates are low. We conducted an exploratory qualitative study to determine
      barriers to CRC screening for New Mexico Hispanics. We found that machismo served
      as a dynamic influence on men's health-seeking behaviors; however, it was
      conceptualized differently by two distinct Hispanic subpopulations, and therefore
      appeared to play a different role in shaping their screening attitudes and
      behaviors. Machismo emerged as more of an influence for Mexican men, who
      expressed concern over colonoscopies being potentially transformative and/or
      stigmatizing, but was not as salient for Hispanos, who viewed the colonoscopy as
      "strictly medical," and were more concerned with discomfort and pain. Findings
      from the study highlight the importance of identifying varying characteristics
      among subpopulations to better understand screening barriers and provide optimal
      CRC screening counseling in primary care settings.

PMID- 22138260
TI  - Differential articulatory movements during Japanese /s/ and /t/ as revealed by MR
      image sequences with tooth visualization.
AB  - OBJECTIVE: To evaluate the spatio-temporal relationships between articulators in
      the anterior oral cavity, during the production of Japanese fricative and plosive
      articulation using our proposed method for tooth visualization in MR image
      sequences. DESIGN: Ten healthy adults without malocclusion participated in the
      study. Customized maxillary and mandibular plates with space around the central
      incisors that was to be filled with MR-compatible contrast medium were made.
      During image-acquisition by a cine magnetic resonance imaging (MRI) technique,
      the subjects repeated vowel-consonant-vowel syllables (/asa/ and /ata/) without
      wearing the plates. The subjects then wore the plates for tooth imaging. All data
      were acquired in the midsagittal plane. Tooth boundaries were superimposed using
      landmarks. Several parameters and spatio-temporal changes in the centre of
      gravity (CoG) of the tongue were measured. RESULTS: During /t/, the duration and
      amount of tongue-to-palate/incisor contact were significantly greater and the
      radius of the inscribed circle between the tongue-maxillary incisor-mandibular
      incisor was significantly shorter than those during /s/. /t/ also had a more
      anteriorly located CoG of the tongue than /s/ during maximum constriction. The
      spatio-temporal changes in the CoG of the tongue were significantly different
      between /asa/ and /ata/. CONCLUSIONS: We conclude that increased tongue-to
      palate/incisor contact and greater anterior closure are necessary for the
      production of Japanese /t/ compared to /s/. With the use of this new method for
      tooth visualization in MR image sequences, it should be possible to evaluate the
      interaction of teeth and other articulators during speech.

PMID- 22138261
TI  - Biomarker detection for the diagnosis of lymph node metastasis from oral squamous
      cell carcinoma.
AB  - Lymph node metastasis is an important prognostic factor in oral squamous cell
      carcinoma. However, the lack of significant biomarkers for lymph node metastasis
      can cause patients to be inappropriately treated and produce a poor prognosis.
      Therefore, there is a need to identify gene sets that are associated with lymph
      node metastasis. In this study, we used three expression datasets obtained from a
      public database and selected candidate gene sets that were related with lymph
      node metastasis from two datasets and a combined dataset. We evaluated the
      selected gene set using OOB error rates in a validation dataset. The gene set
      detected from the combined dataset classified the lymph node status more
      accurately in the validation dataset and clear expression patterns classifying
      the lymph node status based on chromosomal location were observed. The combined
      dataset holds promise for use as a more accurate candidate gene set for the
      diagnosis of lymph node metastasis and the selected gene set could be used for
      biological validation in further studies.

PMID- 22138262
TI  - Pathways and targets--opposite approaches to success?

PMID- 22138263
TI  - [What should we do and what should we not do after an anaesthetic accident. The
      point of view of a medical expert].
AB  - Lawsuits following an anaesthetic accident are fortunately infrequent.
      Anaesthesiologists are mainly sued by parents when the accident led to death or
      permanent brain damage. The aims of this short review are to explain how the
      medical expert is chosen by the court, what are the goals of the mission given by
      the judge, and how to prepare the medical expertise.

PMID- 22138264
TI  - Hydrated phosphorus oxyacids alone and adsorbed on nanosilica.
AB  - Low-temperature (1)N NMR spectroscopy was used to study states of water bound to
      phosphoric and phosphonic acids (phosporus oxyacids, POA) alone or adsorbed onto
      nanosilica OX-50 (specific surface area S(BET)=52 m(2)/g) or A-300 (S(BET)=297
      m(2)/g). Concentrated solutions or weakly hydrated solid POA or dried silica/POA
      powders placed in CCl(4) medium are characterized by different temperature
      dependences of the chemical shift of the proton resonance (delta(H)) because of
      partial dissociation of PO-H bonds strongly affected by water amounts and
      temperature. NMR cryoporometry results show that both small water clusters and
      nanodomains are present at the interfaces of hydrated solid POA and silica/POA
      powders. Quantum chemical calculations of the (1)H NMR spectra demonstrate the
      influence of POA/water cluster structure and dissociation of the PO-H bonds on
      the delta(H) values.

PMID- 22138265
TI  - Complexes of nucleolipid liposomes with single-stranded and double-stranded
      nucleic acids.
AB  - We report on the association of anionic liposomes from POP-Ade:POPC (1-palmitoyl
      2-oleoyl-phosphatidyladenosine and 1-palmitoyl-2-oleoyl-phosphatidylcholine,
      respectively) with single- and double-strand nucleic acids, mediated by Ca(2+)
      bridging. The structural and dynamical features of such complexes are compared
      with those displayed when the nucleolipid is replaced by POPG (1-palmitoyl-2
      oleoyl-sn-phosphatidyl-glycerol), characterized by the same apolar skeleton and
      negative charge as POP-Ade, but lacking the nucleic polar head. For single
      stranded nucleic acids, we demonstrate that specific interactions drive the
      formation of complexes with nucleolipid liposomes, while no association is
      present for POPG-based samples. For double-stranded nucleic acids, Ca(2+)
      bridging promotes association with both liposomal formulations, but the
      corresponding complexes have different structural features, in terms of size,
      overall charge and internal liquid-crystalline structure.

PMID- 22138266
TI  - Production and characterization of biosurfactant from marine Streptomyces species
      B3.
AB  - The present study demonstrates the production and properties of a biosurfactant
      isolated from marine Streptomyces species B3. The production of the biosurfactant
      was found to be higher in medium containing sucrose and lower in the medium
      containing glycerol. Yeast extract was the best nitrogen source for the
      production of the biosurfactant. The isolated biosurfactant reduced the surface
      tension of water to 29 mN/m. The purified biosurfactant was shown critical
      micelle concentrations of 110 mg/l. The emulsifying activity and stability of the
      biosurfactant was investigated at different salinities, pH, and temperature. The
      biosurfactant was effective at very low concentrations over a wide range of
      temperature, pH, and salt concentration. The purified biosurfactant was shown
      strong antimicrobial activity. The biosurfactant was produced from the marine
      Streptomyces sp. using non-hydrocarbon substrates such as sucrose that was
      readily available and not required extensive purification procedure. Streptomyces
      species B3 can be used for microbially enhanced oil recovery process.

PMID- 22138267
TI  - Submicron Y2O3 particles codoped with Eu and Tb ions: size controlled synthesis
      and tuning the luminescence emission.
AB  - Eu(3+) and Tb(3+) codoped Y(2)O(3) submicron particles were prepared using the
      simple urea homogeneous precipitation method. X-ray diffraction patterns revealed
      the synthesized particles to have a pure cubic Y(2)O(3) structure. Field-emission
      scanning electron microscopy and field-emission transmission electron microscopy
      showed that the synthesized particles had almost uniform spherical shapes. The
      luminescence color emission of the synthesized particles could be tuned from red
      due to the effective (5)D(0)->(7)F(j) (j=0, 1, 2 and 3) transitions within Eu(3+)
      to green due to the (5)D(4)->(7)F(5) transition within Tb(3+) by switching the
      excitation wavelength from 255 to 310 nm. Luminescence quenching was observed at
      high dopant concentrations. Strong and effective color-tunable emission is
      expected to find a wide range of applications in industry.

PMID- 22138268
TI  - Characterization of paraffin oil emulsions stabilized by hydroxypropyl
      methylcellulose.
AB  - To study the relationship between emulsion stability and polymer emulsifier
      concentration, the preparation of paraffin oil emulsions by hydroxypropyl
      methylcellulose (HPMC) was carried out with HPMC concentrations below the
      overlapping concentration (C(*)) of HPMC. The stability of the emulsions
      incorporating HPMC was investigated by measuring the creaming velocity, volume
      fraction of emulsified paraffin oil, oil droplet size, and some rheological
      responses such as the stress-strain sweep curve and strain and frequency
      dependences of dynamic viscoelastic moduli. The paraffin oil was almost
      emulsified by HPMC above C(*)/20: the volume fraction of paraffin oil in the
      emulsion was higher than 0.72. Increasing in the HPMC concentration led to
      decreases in both the average oil droplet size and creaming velocity and an
      increase in the yield stress. All emulsions behaved as solid-like viscoelastic
      matter. Additionally, the measured dynamic storage moduli were compared with
      those calculated from a relationship based on functions of the volume fraction of
      oil in the emulsions and Laplace pressure; good agreement between the measured
      and calculated moduli was obtained. On the other hand, at HPMC concentrations
      below C(*)/50, the emulsified paraffin oil became unstable and the oil and the
      HPMC solution eventually separated.

PMID- 22138269
TI  - Adsorption and removal of tetracycline antibiotics from aqueous solution by
      graphene oxide.
AB  - Significant concerns have been raised over pollution of antibiotics including
      tetracyclines in aquatic environments in recent years. Graphene oxide (GO) is a
      potential effective absorbent for tetracycline antibiotics and can be used to
      remove them from aqueous solution. Tetracycline strongly deposited on the GO
      surface via pi-pi interaction and cation-pi bonding. The adsorption isotherm fits
      Langmuir and Temkin models well, and the theoretical maximum of adsorption
      capacity calculated by Langmuir model is 313 mg g(-1), which is approximately in
      a close agreement with the measured data. The kinetics of adsorption fits pseudo
      second-order model perfectly, and it has a better rate constant of sorption (k),
      0.065 g mg(-1) h(-1), than other adsorbents. The adsorption capacities of
      tetracycline on GO decreased with the increase in pH or Na(+) concentration. The
      adsorption isotherms of oxytetracycline and doxycycline on GO were discussed and
      compared.

PMID- 22138270
TI  - Patterns of level and change in self-reported driving behaviors among older
      adults: who self-regulates?
AB  - OBJECTIVES: The present study investigated patterns of self-reported driving
      habits among healthy older adults over 5 years, as well as characteristics that
      distinguished subgroups with different patterns. METHODS: Participants were
      drivers from the control group of the Advanced Cognitive Training for Independent
      and Vital Elderly study at the baseline assessment (N = 597). The outcome was a
      composite of driving frequency, driving space, and perceived driving difficulty.
      Growth mixture models identified classes of participants with different baseline
      scores and change trajectories, and classes were compared in terms of baseline
      sensory, physical, and cognitive functioning. RESULTS: A 3-class model was
      indicated, consisting of 2 classes with intercept differences and stability over
      time, "above-average stable" (39%) and "average stable" drivers (44%), and 1
      class with a lower intercept and negative slope, "decreasers" (17%). Relative to
      stable drivers, decreasers exhibited significantly more depressive symptoms and
      poorer self-rated health, balance, everyday functioning, and speed of processing
      after controlling for age and education (p < .05). DISCUSSION: The majority of
      older drivers maintained their driving over time at different levels, whereas a
      subgroup of individuals with poorer baseline functioning self-regulated by
      reducing their driving. Future studies should determine how such patterns affect
      driving safety.

PMID- 22138271
TI  - Chemopreventive mechanisms of methionine on inhibition of benzo(a)pyrene-DNA
      adducts formation in human hepatocellular carcinoma HepG2 cells.
AB  - This study was designed to investigate the molecular mechanism underlying the
      chemopreventive effects of methionine on benzo[a]pyrene (B[a]P)-DNA adducts
      formation in HepG2 cells. Methionine significantly inhibited B[a]P-DNA adduct
      formation in HepG2 cells. Methionine significantly decreased the cellular uptake
      of [(3)H] B[a]P, but increased the cellular discharge of [(3)H] B[a]P from HepG2
      cells into the media. B[a]P significantly lowered total cellular glutathione
      (GSH) level, but co-cultured with B[a]P and methionine, gradually attenuated
      intracellular GSH levels in a concentration-dependent manner, which was markedly
      higher at 20-500MUM methionine. The cellular proteins of treated cells were
      resolved by 2D-polyacrylamide gel electrophoresis. Proteomic profiles showed that
      phase II enzymes such as glutathione S-transferase (GST) omega-1, GSTM3,
      glyoxalase I (GLO1) and superoxide dismutase (SOD) were down-regulated by B[a]P
      treatment, whereas cathepsin B (CTSB), Rho GDP-dissociation inhibitor alpha (Rho
      GDP-DIA), histamine N-methyltransferase (HNMT), spermidine synthase (SRM) and
      arginase-1 (ARG1) were up-regulated by B[a]P. B[a]P and methionine treatments,
      GST omega-1, GSTM3, GLO1 and SOD were significantly enhanced compared to B[a]P
      alone. Similarly, methionine was effective in diminishing the B[a]P-induced up
      regulation of CTSB, Rho-GDP-DIA, HNMT, SRM and ARG1. Our data suggests that
      methionine might exert a chemoprotective effect on B[a]P-DNA adduct formation by
      attenuating intracellular GSH levels, blocking the uptake of B[a]P into cells, or
      by altering expression of proteins involved in DNA adduct formation.

PMID- 22138272
TI  - Individual muscle contributions to knee joint impedance following a sudden
      perturbation: An in vivo inverted pendulum model.
AB  - Previous research has suggested that muscle forces, generated by reflexes,
      contribute to joint stability prior to the more coordinated voluntary muscle
      forces. The purpose of the current study was to quantify the behaviour of the leg
      muscles, through the calculation of individual muscle contributions to joint
      rotational impedance (MJRI), with a specific interest in the neuromuscular
      contribution in the period following shortly after a sudden knee extension
      perturbation. The knee was selected as an in vivo system to represent an inverted
      pendulum model. Kinematic and sEMG data were collected while subjects were in a
      prone position and exposed to sudden knee extension perturbations. A
      biomechanical model was used to estimate muscle forces and moments about the knee
      and these data were then used to calculate instantaneous MJRI. Data indicated
      that pre-voluntary muscle forces do contribute significantly to MJRI following a
      sudden knee extension perturbation as there was a 40% increase in total MJRI in
      the flexion/extension and valgus/varus axes immediately following the
      perturbation, suggesting their importance in stabilizing the joint immediately
      after a disturbance. Additionally, knowledge of perturbation timing was shown to
      increase anticipatory MJRI levels, pre-perturbation (p<0.05), indicating that it
      is advantageous for the neuromuscular system to prepare for a sudden disturbance.
      In conclusion, the data show that the neuromuscular feedback system significantly
      contributes to MJRI and it is believed that this behaviour enhances joint
      impedance following a sudden knee extension perturbation.

PMID- 22138274
TI  - Acid suppression for reflux disease: "off-the-peg" or a tailored approach?

PMID- 22138273
TI  - Methodological considerations of task and shoe wear on joint energetics during
      landing.
AB  - To better understand methodological factors that alter landings strategies, we
      compared sagittal plane joint energetics during the initial landing phase of drop
      jumps (DJ) vs. drop landings (DL), and when shod vs. barefoot. Surface
      electromyography, kinematic and kinetic data were obtained on 10 males and 10
      females during five consecutive drop landings and five consecutive drop jumps
      (0.45m) when shod and when barefoot. Energy absorption was greater in the DJ vs.
      DL (P=.002), due to increased energy absorption at the hip during the DJ. Joint
      stiffness/impedance was more affected by shoe condition, where overall
      stiffness/impedance was greater in shod compared to barefoot conditions (P=.036).
      Further, hip impedance was greater in shod vs. barefoot for the DL only (via
      increased peak hip extensor moment in DL), while ankle stiffness was greater in
      the barefoot vs. shod condition for the DJ only (via decreased joint excursion
      and increased peak joint moment in DJ vs. DL) (P=.011). DJ and DL place different
      neuromechanical demands upon the lower extremities, and shoe wear may alter
      impact forces that modulate stiffness/impedance strategies. The impact of these
      methodological differences should be considered when comparing landing
      biomechanics across studies.

PMID- 22138275
TI  - Strengthening the case for stool DNA tests as first-line colorectal cancer
      screening: are we there yet?

PMID- 22138276
TI  - Interpreting hepatitis B surface antigen levels: useful clinical test or just
      another confusing assay?

PMID- 22138277
TI  - Hepatic artery compression of the common hepatic duct: direct visualization by
      single-operator peroral cholangioscopy.

PMID- 22138278
TI  - Effects of Euterpe oleracea Mart. (ACAI) extract in acute lung inflammation
      induced by cigarette smoke in the mouse.
AB  - Short term inhalation of cigarette smoke (CS) induces significant lung
      inflammation due to an imbalance of oxidant/antioxidant mechanisms. Acai fruit
      (Euterpe oleracea) has significant antioxidant and anti-inflammatory actions. The
      present study aimed to determine whether oral administration of an acai stone
      extract (ASE) could reduce lung inflammation induced by CS. Thirty C57BL/6 mice
      were assigned to three groups (n=10 each): the Control+A group was exposed to
      ambient air and treated orally with ASE 300 mg/kg/day; the CS group was exposed
      to smoke from 6 cigarettes per day for 5 days; and the CS+A group was exposed to
      smoke from 6 cigarettes per day for 5 days and treated orally with ASE (300
      mg/kg/day). On day 6, all mice were sacrificed. After bronchoalveolar lavage, the
      lungs were removed for histological and biochemical analyses. The CS group
      exhibited increases in alveolar macrophage (AMs) and neutrophil numbers (PMNs),
      myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and
      glutathione peroxidase activities (GPx), TNF-alpha expression, and nitrites
      levels in lung tissue when compared with the control ones (p<0.001 for all
      parameters). The AMs, PMNs, MPO, SOD, CAT, GPx and nitrite were significantly
      reduced by oral administration of ASE when compared with CS group (p<0.001 for
      all parameters, with exception of AMs p<0.01). The present results suggested that
      systemic administration of an ASE extract could reduce the inflammatory and
      oxidant actions of CS. Thus, the results of this study in mice should stimulate
      future studies on ASE as a potential agent to protect against CS-induced
      inflammation in humans.

PMID- 22138279
TI  - [Fine-cut tobacco: a priority for public health and consumer advocacy].
AB  - OBJECTIVES: To study whether fine-cut tobacco poses a problem for public health
      and consumer affairs. METHODS: We analyzed up to 70% of the fine-cut tobacco
      market in Spain. Regarding public health, the contents of nicotine, tar and
      carbon monoxide were analyzed and compared with levels in conventional
      cigarettes. Concerning consumer affairs, the labeling of samples was checked.
      RESULTS: The contents of nicotine, tar and carbon monoxide reached values of 70%,
      85% and 84%, respectively. These values are higher than those allowed in
      conventional cigarettes. A total of 67% of the samples analyzed did not show
      nicotine and tar contents on the labeling. None of the labels showed carbon
      monoxide contents. The presence of labeling per se did not guarantee sufficient
      information for consumers. CONCLUSIONS: Fine-cut tobacco is a problem in both
      public health and consumer affairs. Solutions are required to resolve both
      problems.

PMID- 22138280
TI  - [Analysis of the most prevalent disorders in home-rehabilitation and
      physiotherapy units in the province of Almeria (Spain)].
AB  - OBJECTIVES: To describe the most prevalent disorders in 1753 patients referred to
      home rehabilitation and home physiotherapy units. METHOD: We carried out a cross
      sectional descriptive study. The variables analyzed were age, gender, main
      diagnosis, functional capacity (Barthel Index), physiotherapeutic objectives, the
      treatment applied and the number of sessions. RESULTS: The main diagnoses were
      immobilization effects (29%), hip fracture (16.5%), stroke (13.7%), knee
      replacement (11.9%), hip replacement (4.7%), chronic obstructive pulmonary
      disease (2.6%), and Alzheimer's disease (2.4%). The lowest Barthel Index was
      obtained in Alzheimer's disease, stroke and immobilization effects and the
      highest in patients with knee replacement. The process requiring the highest
      number of sessions for complete recovery was stroke. CONCLUSIONS: Significant
      improvements were confirmed in pre- and post- Barthel Index scores for each of
      the above-mentioned diagnoses, demonstrating greater functional independence
      among patients.

PMID- 22138281
TI  - [Burden of disease in the elderly population in Spain].
AB  - OBJECTIVE: We analyzed the burden of disease in the elderly population in Spain
      in 2008. METHODS: A population-based cross-sectional study was performed to
      calculate the disability-adjusted life years (DALYs) of the Spanish population
      aged >= 60 years old. DALYs are the sum of the number of years of life lost
      (YLLs) and the number of years lived with disability (YLDs). Data sources
      included the national mortality register for YLLs, and inference of Euro-A
      subregion (including Spain) estimates for YLDs. RESULTS: In the elderly
      population, DALYs lost due to all diseases were estimated at 2.1 million. The
      main causes of DALYs were malignancies (21.3%), neuropsychiatric disorders
      (21.1%) and cardiovascular diseases (20.4%). The main specific subcategories were
      dementias, ischemic heart disease, cerebrovascular disease, chronic obstructive
      pulmonary disease, lung cancer, hearing loss and osteoarthritis. CONCLUSIONS:
      Burden of disease analysis allows distinct health problems to be reassessed in
      relation to classical mortality analysis.

PMID- 22138282
TI  - [Pharmaceutical prescription in primary care. SESPAS report 2012].
AB  - In 2010, the Spanish National Health Service (NHS) paid for 958 million
      prescriptions. Given the massive population exposure to medication, the risks
      associated with drug consumption are highly significant from the perspective of
      public health. Areas requiring improvement in primary care prescription include
      overtreatment of patients in low risk situations, undertreatment of those in whom
      medication is indicated, poor patient information, polymedication, self
      medication and the appreciable percentage of preventable adverse effects.
      Surprisingly, most of the pharmaceutical strategies in the NHS have not aimed to
      address these problems but have instead concentrated on reducing pharmaceutical
      expenditure, which is not a problem of pharmaceutical expenditure per se but is
      rather a consequence of "the problems" of prescription (and of the regulation and
      management of pharmaceutical services). Some key elements to improve this
      situation include more integrated healthcare, the development of electronic
      medical records systems, overall strategies to improve safety, and reducing the
      role of the pharmaceutical industry. Macro strategies include creating an agency
      able to objectively assess the additional value provided by a new drug and its
      additional cost, price fixing in line with cost-effectiveness, and exclusion of
      drugs with little or no added value from coverage, etc. Managing prescription
      involves the development of longitudinal patient care programs that incorporate
      clinical actions from different professionals, including whom to treat, how much
      to treat and how to treat.

PMID- 22138283
TI  - [Women's satisfaction with the experience of childbirth: validation of the Mackey
      Childbirth Satisfaction Rating Scale].
AB  - OBJECTIVES: To determine the reliability and the content and construct validity
      of the Mackey Childbirth Satisfaction Rating Scale to measure women's
      satisfaction with labor and delivery. METHODS: The translation-back translation
      method was used to obtain an adapted version of the scale. For the validation
      study, a sample of 325 women who had delivered a healthy neonate through the
      vaginal route was selected. Data collection was performed using a self
      administered questionnaire that included the modified scale, childbirth
      expectations, obstetric variables and sociodemographic characteristics.
      Reliability was assessed in a subsample of 45 women who completed the scale for
      the second time 15-30 days later. The factorial structure and internal
      consistency of the scale were analyzed. Construct validity was evaluated by
      analyzing the relationship between satisfaction with the experience, fulfillment
      of expectations and preferences regarding pain management. RESULTS: In the test
      retest study, an intraclass correlation coefficient of 0.93 was obtained for the
      total scale. Factor analysis identified six factors that explained 69.42% of the
      variance. Cronbach's alpha coefficient was 0.94 for the total scale, ranging from
      0.72 to 0.96 for the subscales. Satisfaction with the experience of childbirth
      was higher among women whose expectations were met and among those who accessed
      the pain relief method chosen. CONCLUSIONS: This scale is a useful instrument to
      measure women's satisfaction with the experience of childbirth, adapted to our
      context and with good psychometric properties.

PMID- 22138284
TI  - Is there an association between suicide attempt and delay of initiation of mood
      stabilizers in bipolar I disorder?
AB  - BACKGROUND: Little is known about the extent to which delay of initiation of mood
      stabilizing treatment may influence outcomes in bipolar patients (BP). In this
      study, our aim was to investigate the association between delay of mood
      stabilizer treatment in bipolar patients and lifetime history of suicide
      attempts. METHOD: A consecutive sample of 268 bipolar I outpatients from two
      teaching hospitals in Brazil was recruited. The assessment included a socio
      demographic history form, a clinical interview regarding clinical variables and
      the Structured Clinical Interview for DSM-IV. Participants were divided into
      three groups: BP that initiated the first mood stabilizer in the same year of the
      first episode of the disease (FMS<=1), between 1 and 5 years after the first
      episode of the disease (1<FMS<=5), and after 5 years after the first episode of
      BD (FMS>5). RESULTS: The mean time from the first episode until the first mood
      stabilizer medication was 8.6 years (SD 9.8 years). The FMS>5 group, showed a
      higher lifetime prevalence of suicide attempts than the other two groups
      (PR=1.75, 95% CI: 1.24-2.47), p=0.001. These results remained significant after
      adjusting for potential confounders, (PR=1.82, 95% CI: 1.29-2.60), p=0.001.
      LIMITATIONS: This study evaluated patients retrospectively and does not permit a
      cause-effect relationship. CONCLUSION: The present study supports the importance
      of early diagnosis and early intervention for BP in order to limit the
      potentially lethal impact of the disease.

PMID- 22138285
TI  - Depression prevalence and associated factors among Alaska Native people: the
      Alaska education and research toward health (EARTH) study.
AB  - BACKGROUND: Few studies have investigated depression among Alaska Native people
      (ANs). Depression prevalence and associated factors among EARTH Alaska study
      participants are described. METHODS: The nine-item Patient Health Questionnaire
      (PHQ-9) assessed depression among 3771 ANs. Participants with PHQ-9 scores>=10
      out of 27 were classified as positive for depression. Logistic regression
      analyses evaluated odds of scoring positive versus negative for depression by
      demographic, cultural, then health and lifestyle factors. RESULTS: Twenty percent
      of women and 13% of men scored positive for depression. Univariate and
      multivariate models were fit separately for men and women. Among demographic
      factors, below median income was associated with positive depression scores for
      both genders. Among men, odds of depression were higher if unmarried and/or if
      highest educational level was less than high school. Women 34 to 59 years of age
      had increased odds of scoring positive. Little or no identification with tribal
      tradition was associated with increased odds of depression in women and decreased
      odds in men. For both genders, chronic physical conditions and poorer self
      reported health were associated with positive depression scores then binge
      alcohol drinking and current tobacco use increased odds of depression among women
      only. LIMITATIONS: Factors analyzed were self-reported without clinician follow
      up in a non-random convenience sample of adults. CONCLUSIONS: Depression is
      common among ANs with rates comparable to other indigenous cross-sectional
      investigations. Depression is associated with lower income and poorer physical
      health. Prevention and intervention efforts should consider gender as other
      associated factors varied between men and women.

PMID- 22138287
TI  - Investigations into matrix components affecting the performance of the official
      bioassay reference method for quantitation of paralytic shellfish poisoning
      toxins in oysters.
AB  - Significant differences previously observed in the determination of paralytic
      shellfish poisoning toxins (PSTs) in oysters using official method AOAC 2005.06
      and 959.08 were investigated in detail with regard to possible matrix effects.
      Method AOAC 2005.06 gave results 2-3 times higher than the mouse bioassay method,
      959.08, differences thought to be due to underestimation of PSTs by the mouse
      bioassay. In order to prove the cause of these large differences, work was
      conducted here to examine the presence and effects of matrix components on the
      performance of each of the two assays. A range of oyster, cockle and mussel
      samples were extracted using the AOAC 959.08 hydrochloric acid (HCl) extraction
      method and analysed for PSP by both MBA and LC-FLD. In addition, extracts were
      analysed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for metals as
      well as being subjected to a range of nutritional testing methods. Whilst there
      was no evidence for effect of nutritional components on either assay, ICP-MS
      analysis revealed a relationship between samples exhibiting the largest
      differences in relative method performance, specifically those with the largest
      LC-FLD/MBA toxicity ratio, and samples containing the highest concentrations of
      zinc and manganese. In order to prove the potential effect of the metals on
      either the LC-FLD and/or MBA assays, HCl extracts of a range of shellfish were
      subjected to a number of matrix modifications. Firstly, a number of PSP-positive
      oyster samples were processed to reduce the concentrations of metals within the
      extracts, without significantly reducing the concentrations of PSTs. Secondly, a
      range of mussel and cockle extracts, plus a standard solution of saxitoxin di
      hydrochloride were spiked at variable concentrations of zinc. All treated and non
      treated extracts, plus a number of controls were subjected to ICP-MS, LC-FLD and
      MBA testing. Results proved the absence of any effect of metals on the
      performance of the LC-FLD, whilst showing a large suppressive effect of the
      metals on the MBA. As such, the results show the performance of the official MBA
      is potentially unsafe for application to the routine monitoring of PSP toxicity
      in oysters or in any other shellfish found to contain high concentrations of
      metal ions.

PMID- 22138286
TI  - MRI of weight bearing and movement.
AB  - Conventional, static magnetic resonance imaging (MRI) is able to provide a vast
      amount of information regarding the anatomy and pathology of the musculoskeletal
      system. However, patients, especially those whose pain is position dependent or
      elucidated by movement, may benefit from more advanced imaging techniques that
      allow for the acquisition of functional information. This manuscript reviews a
      variety of advancements in MRI techniques that are used to image the
      musculoskeletal system dynamically, while in motion or under load. The
      methodologies, advantages and drawbacks of stress MRI, cine-phase contrast MRI
      and real-time MRI are discussed as each has helped to advance the field by
      providing a scientific basis for understanding normal and pathological
      musculoskeletal anatomy and function. Advancements in dynamic MR imaging will
      certainly lead to improvements in the understanding, prevention, diagnosis and
      treatment of musculoskeletal disorders. It is difficult to anticipate that
      dynamic MRI will replace conventional MRI, however, dynamic MRI may provide
      additional valuable information to findings of conventional MRI.

PMID- 22138288
TI  - CCL2 increases MMP-9 expression and cell motility in human chondrosarcoma cells
      via the Ras/Raf/MEK/ERK/NF-kappaB signaling pathway.
AB  - Chondrosarcoma is a type of highly malignant tumor with a potent capacity to
      invade locally and cause distant metastasis. Chondrosarcoma shows a predilection
      for metastasis to the lungs. Chemokine ligand 2 (CCL2), also known as monocyte
      chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family that is
      associated with the disease status and outcomes of cancers. However, the effect
      of CCL2 on migration activity in human chondrosarcoma cells is mostly unknown.
      Here we found that CCL2 increased the migration and expression of matrix
      metalloproteinase (MMP)-9 in human chondrosarcoma cells. CCL2-mediated migration
      and MMP-9 up-regulation were attenuated by CCR2, Ras, Raf-1, and MEK inhibitor.
      Activation of the Ras, Raf-1, MEK, ERK, and NF-kappaB signaling pathway after
      CCL2 treatment was demonstrated, and CCL2-induced expression of MMP-9 and
      migration activity were inhibited by the specific inhibitor, and mutant of Ras,
      Raf-1, MEK, ERK, and NF-kappaB cascades. Taken together, our results indicated
      that CCL2 enhances the migration of chondrosarcoma cells by increasing MMP-9
      expression through the CCR2 receptor, Ras, Raf-1, MEK, ERK, and NF-kappaB signal
      transduction pathway.

PMID- 22138290
TI  - Sacral ganglioneuroma.

PMID- 22138289
TI  - Cell-specific effects of miR-221/222 in vessels: molecular mechanism and
      therapeutic application.
AB  - MicroRNAs (miRNAs) are noncoding RNAs that impact almost every aspect of biology
      and disease. Until now, the cell-specific effects of miRNAs in cardiovascular
      system have not been established. In the current study, the cellular functions of
      miR-221 and miR-222 (miR-221/222) in vascular smooth muscle cells (VSMCs) and
      vascular endothelial cells (ECs) were compared. In cultured cells, we identified
      that the effects of miR-221/222 on proliferation, migration, and apoptosis are
      opposite between VSMCs and ECs. In VSMCs, miR-221/222 had effects of pro
      proliferation, pro-migration, and anti-apoptosis. In contrast, miR-221/222 had
      effects of anti-proliferation, anti-migration, and pro-apoptosis in ECs. The
      different expression profiles of their target genes, p27(Kip1), p57(kip2), and c
      kit between the two cell types might be related to the opposite effects. Finally,
      the opposite cellular effects of miR-221/222 were verified in vivo in balloon
      injured rat carotid artery as demonstrated by different consequences in
      neointimal growth and re-endothelialization. The results suggest that the
      biological functions of miR-221/222 in vascular walls are cell-specific. The
      opposite cellular effects of miR-221/222 on VSMCs and ECs may have important
      therapeutic applications in many vascular diseases such as atherosclerosis and
      restenosis after angioplasty.

PMID- 22138291
TI  - [Treatment of colorectal cancer: present advances].

PMID- 22138292
TI  - [Surgical treatment of liver metastasis in patients with colorectal cancer].
AB  - Half of patients with colorectal cancer have liver metastasis during their
      illness. Surgical resection of metastases represents the only curative treatment
      with prolonged survival in more than 50 % of patients. The aim of liver resection
      is complete excision of the lesions with histological negative margins while
      preserving sufficient functional liver parenchyma. In patients with diffuse liver
      disease, the radiofrequency ablation of metastases may be associated with
      surgical resection. The use of portal vein remobilization and neoadjuvant
      chemotherapy can also increase the number of patients for curative treatment.
      Despite this progress, from 50 to 60 % of patients relapse after complete
      resection of MHCCR. Surgical treatment of recurrent aggressive and effective
      chemotherapy allows the prolonged survival of these patients. The modern
      treatment of liver metastasis of colorectal cancers can be envisaged as part of a
      multidisciplinary approach to increase the number of patients for curative
      treatment.

PMID- 22138293
TI  - [Practical questions around individual with a pacemaker or an implantable
      cardioverter defibrillator].
AB  - An individual with a pacemaker can ask his GP for information about potential
      problems associated with the device. Should a pacemaker continue to be used by
      end-of-life patients? Should a pacemaker be stopped in a limited care situation?
      What precautions should be taken when treating a patient with a pacemaker?
      Pacemakers and implantable defibrillators are sensitive to electromagnetic
      interference (EMI). Medically, MRIs are theoretically contraindicated, even
      though examinations could be performed without a major problem, and special
      precautions should be taken when using an electrosurgical cutter or radiotherapy.
      In case of death, a doctor or embalmer must remove the patient's pacemaker due to
      its risk of explosion during cremation. Doctors who sign cremation forms have a
      legal obligation to provide such information. It may affect an employee's ability
      to work. Are there some professions that are not well suited for individuals with
      a pacemaker?

PMID- 22138295
TI  - [Falsely increased urinary normetanephrine levels during sulfasalazine
      treatment].

PMID- 22138296
TI  - The role of nitric oxide in orofacial pain.
AB  - Nitric oxide (NO) is a free radical gas that has been shown to be produced by
      nitric oxide synthase (NOS) in different cell types and recognized to act as a
      neurotransmitter or neuromodulator in the nervous system. NOS isoforms are
      expressed and/or can be induced in the related structures of trigeminal nerve
      system, in which the regulation of NOS biosynthesis at different levels of gene
      expression may allow for a fine control of NO production. Several lines of
      evidence suggest that NO may play a role through multiple mechanisms in orofacial
      pain processing. This report will review the latest evidence for the role of NO
      involved in orofacial pain and the potential cellular mechanisms are also
      discussed.

PMID- 22138297
TI  - MAPK- and PKC/CREB-dependent induction of interleukin-11 by the environmental
      contaminant formaldehyde in human bronchial epithelial cells.
AB  - Formaldehyde (FA) is a volatile organic compound (VOC), considered as a major
      indoor air pollutant and suspected to favor the development of inflammatory lung
      diseases. The present study was aimed at identifying cytokines/chemokines
      targeted by FA in human lung cells. This VOC was demonstrated to up-regulate
      interleukin-11 (IL-11) mRNA and secretion levels in a dose-dependent manner in
      cultured lung epithelial BEAS-2B cells. It concomitantly induced mRNA expression
      of transforming growth factor (TGF)-beta1, a fibrogenic marker regulated by IL
      11. FA was also found to trigger an early phosphorylation of p38 and
      extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinases
      (MAPKs) in BEAS-2B cells, whose inhibition by ERK and p38 MAPK chemical
      inhibitors (U0126 and SB203580, respectively) counteracted FA-mediated induction
      of IL-11. In addition, FA increased phosphorylation of cAMP response element
      binding protein (CREB) and the use of small-interfering RNA targeting CREB
      demonstrated that this transcription factor was required for the up-regulation of
      IL-11 by FA. Implication of protein kinase C (PKC) in FA-induced IL-11 expression
      was moreover demonstrated by using RO-31-8220, a PKC inhibitor. We finally showed
      using SB203580 and RO-31-8220 that phosphorylation of CREB and CREB-promoter
      activity induced by FA are under the control of both p38 MAPK and PKC. Taken
      together, the results showed that FA uses different pathways to induce IL-11
      expression in lung BEAS-2B cells. IL-11, well-known to contribute to lung
      inflammatory diseases, appears thus as a molecular target of FA, which could be
      involved in putative deleterious inflammatory and fibrogenic pulmonary effects of
      this VOC.

PMID- 22138300
TI  - Molecular typing of adenoviruses in pediatric respiratory infections in Buenos
      Aires, Argentina (1999-2010).
AB  - BACKGROUND: The human adenovirus (HAdV) types most commonly found in respiratory
      samples belong to HAdV species C (HAdV-C1, -C2, -C5, and -C6) and to HAdV species
      B (HAdV-B3 and -B7). Several studies in South America have shown the association
      between severe respiratory infections and subspecies B1. OBJECTIVES: The aim of
      this study was to identify the adenovirus types associated with acute lower
      respiratory tract infections in children, found as single or coinfections,
      throughout a 12-year period. STUDY DESIGN: All samples that tested positive for
      adenovirus by immunofluorescence assay from January 1999 to December 2010 were
      typed by evaluating a set of four viral genes (E1A, VA, hexon and fiber).
      Quantitative PCRs for HAdV-B and HAdV-C species were performed to compare the
      viral load found in single infections and coinfections. RESULTS: From a total of
      743 HAdV, 654 (88%) were single infections and 89 (12%) coinfections. From the
      654 single HAdV infections, members of four species were present: species B
      (n=492, 75.23%), species C (n=138, 21.1%), species E (n=19, 2.91%), and species D
      (n=5, 0.76%). Only members of species B (n=109, 57.67%) and species C (n=80,
      42.33%) were detected in coinfections. HAdV-B7 and HAdV-B3 were the most
      prevalent types (n=308, 36.54%; n=230, 27.28% respectively) and HAdV-C1, -C2, 
      E4, -C5, -C6, -D8, -B11, -B14 and -B21 were also detected. Viral loads for
      species C viruses were higher in single infections than in coinfections (p<0.01),
      whereas the opposite was observed for species B viruses (p<0.0001). CONCLUSIONS:
      This study provides a thorough description of adenovirus circulation and
      diversity in Buenos Aires in a 12-year period. The high proportion of
      coinfections found in this work shows that this phenomenom might be more common
      than expected.

PMID- 22138298
TI  - Reciprocal induction of simple organogenesis by mouse kidney progenitor cells in
      three-dimensional co-culture.
AB  - Kidney development is regulated by a coordinated reciprocal induction of
      metanephric mesenchymal (MM) and ureteric bud (UB) cells. Here, established MM
      and UB progenitor cell lines were recombined in three-dimensional Matrigel
      implants in SCID mice. Differentiation potential was examined for changes in
      phenotype, organization, and the presence of specialized proteins using
      immunofluorescence and bright-field and electron microscopy. Both cell types,
      when grown alone, did not develop into specialized structures. When combined, the
      cells organized into simple organoid structures of polarized epithelia with
      lumens surrounded by capillary-like structures. Tracker experiments indicated the
      UB cells formed the tubuloid structures, and the MM cells were the source of the
      capillary-like cells. The epithelial cells stained positive for pancytokeratin,
      the junctional complex protein ZO-1, collagen type IV, as well as UB and
      collecting duct markers, rearranged during transfection (RET), Dolichos biflorus
      lectin, EndoA cytokeratin, and aquaporin 2. The surrounding cells expressed alpha
      smooth muscle actin, vimentin, platelet endothelial cell adhesion molecule 1
      (PECAM), and aquaporin 1, a marker of vasculogenesis. The epithelium exhibited
      apical vacuoles, microvilli, junctional complexes, and linear basement membranes.
      Capillary-like structures showed endothelial features with occasional pericytes.
      UB cell epithelialization was augmented in the presence of MM cell-derived
      conditioned medium, glial-derived neurotrophic factor (GDNF), hepatocyte growth
      factor (HGF), or fibronectin. MM cells grown in the presence of UB-derived
      conditioned medium failed to undergo differentiation. However, UB cell-derived
      conditioned medium induced MM cell migration. These studies indicate that
      tubulogenesis and vasculogenesis can be partially recapitulated by recombining
      individual MM and UB cell lineages, providing a new model system to study
      organogenesis ex vivo.

PMID- 22138299
TI  - Constitutive TL1A expression under colitogenic conditions modulates the severity
      and location of gut mucosal inflammation and induces fibrostenosis.
AB  - Intestinal fibrostenosis is a hallmark of severe Crohn's disease and can lead to
      multiple surgeries. Patients with certain TNFSF15 variants overexpress TL1A. The
      aim of this study was to determine the effect of TL1A overexpression on
      intestinal inflammation and the development of fibrostenosis. We assessed the in
      vivo consequences of constitutive TL1A expression on gut mucosal inflammation and
      fibrostenosis using two murine models of chronic colitis. In the dextran sodium
      sulfate (DSS) and adoptive T-cell transfer models, there was proximal migration
      of colonic inflammation, worsened patchy intestinal inflammation, and long gross
      intestinal strictures in Tl1a transgenic compared to wild-type littermates. In
      the DSS model, myeloid- and T-cell-expressing Tl1a transgenic mice had increased
      T-cell activation markers and interleukin-17 expression compared to wild-type
      mice. In the T-cell transfer model, Rag1(-/-) mice receiving Tl1a transgenic T
      cells had increased interferon-gamma expression but reduced T-helper 17 cells and
      IL-17 production. Narrowed ureters with hydronephrosis were found only in the
      Tl1a transgenic mice in all chronic colitis models. In human translational
      studies, Crohn's disease patients with higher peripheral TL1A expression also
      exhibited intestinal fibrostenosis and worsened ileocecal inflammation with
      relative sparing of rectosigmoid inflammation. These data show that TL1A is an
      important cytokine that not only modulates the location and severity of mucosal
      inflammation, but also induces fibrostenosis.

PMID- 22138301
TI  - Dynamic changes in HCV RNA levels and viral quasispecies in a patient with
      chronic hepatitis C after telaprevir-based treatment.
AB  - BACKGROUND: Telaprevir is a selective inhibitor of the hepatitis C virus NS3.4A
      serine protease. Treatment with telaprevir resulted in a rapid HCV-RNA decline in
      chronic hepatitis C genotype 1 patients. OBJECTIVES: To report the clinical and
      viral course of a patient treated with telaprevir in combination with pegylated
      interferon-alpha-2a and ribavirin in a Phase 2 clinical trial (PROVE3). STUDY
      DESIGN: This previous non-responder to interferon based therapy was treated for
      40 weeks with a telaprevir, pegylated interferon alpha-2a, and ribavirin regimen.
      Viral sequencing and phylogenetic analysis were performed before, during and
      after therapy. RESULTS: The patient, a 54 years old male patient, experienced a
      viral relapse 4 weeks post-treatment and HCV-RNA levels continued to increase 14
      weeks post-treatment (150,000 IU/mL). The viral population, which was wild type
      at baseline, consisted of only V36A variants at both of these post-treatment
      timepoints. Subsequently, this patient had a transient disappearance of HCV-RNA
      for more than 1 year in the absence of antiviral therapy. Thereafter, HCV-RNA
      reappeared again with a viral population consisting of only wild type virus.
      Phylogenetic analysis of NS3.4A corresponded with a viral population bottleneck
      resulting in changes in viral quasispecies. CONCLUSION: In this case report,
      significant viral load reductions resulted in a genetic bottleneck leading to a
      reduction of variability in the hepatitis C viral population. We hypothesize that
      the reduction in viral heterogeneity potentially led to a reduced viral capacity
      to adapt to a host immune response leading to a transient loss of detectable HCV
      RNA.

PMID- 22138303
TI  - Apo J/clusterin expression and secretion: evidence for 15-deoxy-Delta(12,14)
      PGJ(2)-dependent mechanism.
AB  - Cyclooxygenase-2 (Cox-2) and Apo J/clusterin are involved in inflammatory
      resolution and have each been reported to inhibit NF-kappaB signalling. Using a
      well-validated rat pheochromocytoma (PC12) cell culture model of Cox-2 over
      expression the current study investigated inter-dependence between Cox-2 and
      clusterin with respect to induction of expression and impact on NF-kappaB
      signalling. Both gene expression and immunoblot analysis confirmed that
      intracellular and secreted levels of clusterin were elevated in Cox-2 over
      expressing cells (PCXII). Clusterin expression was increased in control (PCMT)
      cells in a time- and dose-dependent manner by 15-deoxy-Delta(12,14)-prostaglandin
      J(2) (15d-PGJ(2)), but not PGE(2), and inhibited in PCXII cells by
      pharmacological Cox inhibition. In PCXII cells, inhibition of two transcription
      factors known to be activated by 15d-PGJ(2), heat shock factor 1 (HSF-1) and
      peroxisome proliferator activated receptor (PPAR)gamma, by transcription factor
      oligonucleotide decoy and antagonist (GW9662) treatment, respectively, reduced
      clusterin expression. While PCXII cells exhibited reduced TNF-alpha-induced cell
      surface ICAM-1 expression, IkB phosphorylation and degradation were similar to
      control cells. With respect to the impact of Cox-2-dependent clusterin
      upregulation on NF-kappaB signalling, basal levels of IkappaB were similar in
      control and PCXII cells, and no evidence for a physical association between
      clusterin and phospho-IkappaB was obtained. Moreover, while PCXII cells exhibited
      reduced NF-kappaB transcriptional activity, this was not restored by clusterin
      knock-down. These results indicate that Cox-2 induces clusterin in a 15d-PGJ(2)
      dependent manner, and via activation of HSF-1 and PPARgamma. However, the results
      do not support a model whereby Cox-2/15d-PGJ(2)-dependent inhibition of NF-kappaB
      signalling involves clusterin.

PMID- 22138302
TI  - Preferential interactions between ApoE-containing lipoproteins and Abeta revealed
      by a detection method that combines size exclusion chromatography with non
      reducing gel-shift.
AB  - The association between apolipoprotein E (apoE) and amyloid-beta peptide (Abeta)
      may significantly impact the function of both proteins, thus affecting the
      etiology of Alzheimer's disease (AD). However, apoE/Abeta interactions remain
      fundamentally defined by the stringency of the detection method. Here we use size
      exclusion chromatography (SEC) as a non-stringent approach to the detection of
      apoE/Abeta interactions in solution, specifically apoE and both endogenous and
      exogenous Abeta from plasma, CSF and astrocyte conditioned media. By SEC
      analysis, Abeta association with plasma and CNS lipoproteins is apoE-dependent.
      While endogenous Abeta elutes to specific human plasma lipoproteins distinct from
      those containing apoE, it is the apoE-containing lipoproteins that absorb excess
      amounts of exogenous Abeta40. In human CSF, apoE, endogenous Abeta and
      phospholipid elute in an almost identical profile, as do apoE, exogenous Abeta
      and phospholipid from astrocyte conditioned media. Combining SEC fractionation
      with subsequent analysis for SDS-stable apoE/Abeta complex reveals that apoE
      containing astrocyte lipoproteins exhibit the most robust interactions with
      Abeta. Thus, standardization of the methods for detecting apoE/Abeta complex is
      necessary to determine its functional significance in the neuropathology
      characteristic of AD. Importantly, a systematic understanding of the role of apoE
      containing plasma and CNS lipoproteins in Abeta homeostasis could potentially
      contribute to identifying a plasma biomarker currently over-looked because it has
      multiple components.

PMID- 22138304
TI  - Vitamin E, signalosomes and gene expression in T cells.
AB  - CD4+T cells from aged humans or mice show significant reductions in IL-2
      production upon activation. The resulting decreased proliferation is linked to
      higher risks of infection in the elderly. Several lines of evidence indicate that
      intrinsic defects preferentially affecting the naive subset of CD4+T cells
      contribute to this reduced IL-2 production. Comparison of the biochemical
      pathways that transduce activation signals from the T cell receptor to the IL-2
      promoter in young and old CD4+T cells has demonstrated age-related impairments at
      initial molecular events, in particular the phosphorylation of kinases and
      adapter proteins involved in the formation of signalosomes - complex multiprotein
      assemblies that provide the framework for effective signal transduction. Confocal
      microscopy has demonstrated a series of age-related impairments in effective
      immune synapse formation. Vitamin E can reverse many of these CD4+T cell age
      associated defects, including reduced levels of phosphorylation of critical
      signaling/adapter proteins as well as defective immune synapse formation. Vitamin
      E also enhances IL-2 production, expression of several cell cycle control
      proteins, and proliferation. Although the precise mechanisms underlying this
      effect are not understood, it is possible that this antioxidant lipophilic
      vitamin can prevent the propagation of polyunsaturated fatty acid peroxidation in
      the cell membrane, influence the biochemical characteristics of specific lipid
      bilayer microdomains involved in signal transduction, modulate the activity of
      kinases/phosphatases, or interact with intracellular receptors.

PMID- 22138305
TI  - Modifications of ribonuclease A induced by p-benzoquinone.
AB  - The nature of ribonuclease A (RNase) modifications induced by p-benzoquinone
      (pBQ) was investigated using several analysis methods. SDS-PAGE experiments
      revealed that pBQ was efficient in producing oligomers and polymeric aggregates
      when RNase was incubated with pBQ. The fluorescence behavior and anisotropy
      changes of the modified RNase were monitored for a series of incubation reactions
      where RNase (0.050 mM) was incubated with pBQ (0.050, 0.25, 0.50, 1.50 mM) at 37 
      degrees C in phosphate buffer (pH 7.0, 50 mM). The modified RNase exhibited less
      intense fluorescence and slightly higher anisotropy than the unmodified RNase. UV
      Vis spectroscopy indicated that pBQ formed covalent bonds to the modified RNase.
      Confocal imaging analysis confirmed the formation of the polymeric RNase
      aggregates with different sizes upon exposure of RNase to high concentrations of
      pBQ. The interaction between the modified RNase and salts affecting
      biomineralization of salts was also investigated by scanning electron microscopy.
      Overall, our results show that pBQ can induce formation of both RNase adducts and
      aggregates thus providing a better understanding of its biological activity.

PMID- 22138306
TI  - Sero-prevalence of Neospora caninum and Besnoitia besnoiti in South Australian
      beef and dairy cattle.
AB  - A serological survey for Neospora caninum and Besnoitia besnoiti was carried out
      in beef and dairy cattle in South Australia. Serum samples of dairy cattle
      (n=133) from 9 properties and tank milk samples from a further 122 dairy herds
      were tested. An additional 810 sera from beef cattle from 51 properties were also
      tested. Testing at the individual animal level by IDEXX NEOSPORA X2 Ab test ELISA
      revealed a low prevalence of N. caninum antibodies of only 2.7% (95% CI; 1.6
      3.7%) sera positive, as did the milk testing that showed 2.5% (95% CI; 1.4-3.6%)
      of tank milks being positive. At the herd level, 29.4% (95% CI; 16.9-41.9%) of
      beef, and 44.4% (95% CI; 12.0-76.9%) of dairy cattle herds showed serum
      antibodies. The highest within-herd prevalence in beef was 20% and 25%in dairy,
      which explains the low herd prevalence in dairy detected by bulk milk testing.
      Testing for B. besnoiti antibodies by PrioCHECK((r)) Besnoitia Ab 2.0 ELISA
      initially identified 18.4% (95% CI: 15.8-21.0%) of 869 individual cattle sera as
      positive by ELISA at the manufacturer's suggested cut-off threshold (15 PP).
      Additional tests by immunoblot and IFAT, however, could not confirm any of the
      ELISA results. The use of a higher (40 PP) threshold in the ELISA is suggested to
      improve specificity. There is thus no evidence of B. besnoiti infection in South
      Australian cattle.

PMID- 22138307
TI  - Unprecedented synthesis, in vitro and in vivo anti-cancer evaluation of novel
      triazolonaphthalimide derivatives.
AB  - An efficient synthesis method for fusing triazole ring onto the naphthalimide
      core was described. The anti-cancer activities of the generated
      triazolonaphthalimide derivatives were evaluated with five cancer cell lines. The
      compounds generally displayed higher potency than amonafide. 4d,4e carrying two
      amino side chains showed the strongest cytotoxicities. N-oxide 5, a prodrug of
      4a, was designed and synthesized. The agent was expected to be activated under
      the hypoxic condition in tumor tissue. Compared with 4a, 5 manifested much lower
      cytotoxicity both in cancer cell lines and human normal cells in the in vitro
      assays. However, N-oxide 5 performed potent anti-cancer activity in vivo using S
      180 sarcoma bearing mice. All the results suggested that 5 was a promising anti
      cancer agent.

PMID- 22138308
TI  - Identification of new aminoacid amides containing the imidazo[2,1-b]benzothiazol
      2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling.
AB  - The Met receptor tyrosine kinase is a promising target in anticancer therapies
      for its role during tumor evolution and resistance to treatment. It is
      characterized by an unusual structural plasticity as its active site accepts
      different inhibitor binding modes. Such feature can be exploited to identify
      distinct agents targeting tumor dependence and/or resistance by oncogenic Met.
      Here we report the identification of bioactive agents, featuring a new 4
      (imidazo[2,1-b]benzothiazol-2-yl)phenyl moiety, targeting cancer cells dependent
      on oncogenic Met. One of these compounds (7c; Triflorcas) impairs survival,
      anchorage-independent growth, and in vivo tumorigenesis, without showing side
      effects. Our medicinal chemistry strategy was based on an in-house Met-focused
      library of aminoacid-amide derivatives enriched through structure-based computer
      modeling, taking into account the Met multiple-binding-mode feature. Altogether,
      our findings show how a rational structure-based drug design approach coupled to
      cell-based drug evaluation strategies can be applied in medicinal chemistry to
      identify new agents targeting a given oncogenic-dependency setting.

PMID- 22138309
TI  - Synthesis and biological evaluation of cyclopentane-linked alkyl phosphocholines
      as potential anticancer agents that act by inhibiting Akt phosphorylation.
AB  - Three new series of novel alkylphosphocholine (APC) derivatives containing a
      cyclopentane ring near the phosphocholine head group were synthesized. In the
      first set of analogues, the phosphocholine head group was attached to the
      secondary alcohol of trans-2-(hydroxymethyl)cyclopentanol, whereas in the second
      and third sets of analogues, the phosphocholine head group was linked to the
      primary alcohol of trans- and cis-2-(hydroxymethyl)cyclopentanol, respectively.
      Of the compounds synthesized, compound 6d most potently inhibited Akt
      phosphorylation with an IC(50) value of 3.6 MUM, its potency was greater than the
      reference compounds miltefosine, perifosine, and erufosine. Compounds 6b and 6d
      exhibited the most potent growth-inhibitory effects on A549, MCF-7, and KATO-III
      human cancer cell lines. These compounds also showed more active anti
      proliferative effects than the reference compounds. Importantly, the cytotoxic
      effects of these compounds on A549 cell line were proportional to their abilities
      to inhibit Akt phosphorylation, which supports that these synthesized APC
      compounds are novel inhibitors of the Akt cell survival pathway.

PMID- 22138311
TI  - Cross-language activation in children's speech production: evidence from second
      language learners, bilinguals, and trilinguals.
AB  - In five experiments, we examined cross-language activation during speech
      production in various groups of bilinguals and trilinguals who differed in
      nonnative language proficiency, language learning background, and age. In
      Experiments 1, 2, 3, and 5, German 5- to 8-year-old second language learners of
      English, German-English bilinguals, German-English-Language X trilinguals, and
      adult German-English bilinguals, respectively, named pictures in German and in
      English; in Experiment 4, 6- to 8-year-old German monolinguals named pictures in
      German. In both language conditions, cognate status was manipulated. We found
      that the bidirectional cognate facilitation effect was significant in all groups
      except the German monolinguals (Experiment 4) and, critically, the child second
      language learners (Experiment 1) in whom only native language (L1) German had an
      effect on second language (L2) English. The findings demonstrate how the
      integration of languages into a child's system follows a developmental path that,
      at lower levels of proficiency, allows only limited cross-language activation.
      The results are interpreted against the backdrop of the developing language
      systems of the children both for early second language learners and for early bi-
      and trilinguals.

PMID- 22138310
TI  - Genetic background effects on age-related hearing loss associated with Cdh23
      variants in mice.
AB  - Inbred strain variants of the Cdh23 gene have been shown to influence the onset
      and progression of age-related hearing loss (AHL) in mice. In linkage
      backcrosses, the recessive Cdh23 allele (ahl) of the C57BL/6J strain, when
      homozygous, confers increased susceptibility to AHL, while the dominant allele
      (Ahl+) of the CBA/CaJ strain confers resistance. To determine the isolated
      effects of these alleles on different strain backgrounds, we produced the
      reciprocal congenic strains B6.CBACa-Cdh23(Ahl)(+) and CBACa.B6-Cdh23(ahl) and
      tested 15-30 mice from each for hearing loss progression. ABR thresholds for 8
      kHz, 16 kHz, and 32 kHz pure-tone stimuli were measured at 3, 6, 9, 12, 15 and 18
      months of age and compared with age-matched mice of the C57BL/6J and CBA/CaJ
      parental strains. Mice of the C57BL/6N strain, which is the source of embryonic
      stem cells for the large International Knockout Mouse Consortium, were also
      tested for comparisons with C57BL/6J mice. Mice of the C57BL/6J and C57BL/6N
      strains exhibited identical hearing loss profiles: their 32 kHz ABR thresholds
      were significantly higher than those of CBA/CaJ and congenic strain mice by 6
      months of age, and their 16 kHz thresholds were significantly higher by 12
      months. Thresholds of the CBA/CaJ, the B6.CBACa-Cdh23(Ahl)(+), and the CBACa.B6
      Cdh23(ahl) strain mice differed little from one another and only slightly
      increased throughout the 18-month test period. Hearing loss, which corresponded
      well with cochlear hair cell loss, was most profound in the C57BL/6J and
      C57BL/6NJ strains. These results indicate that the CBA/CaJ-derived Cdh23(Ahl)(+)
      allele dramatically lessens hearing loss and hair cell death in an otherwise
      C57BL/6J genetic background, but that the C57BL/6J-derived Cdh23(ahl) allele has
      little effect on hearing loss in an otherwise CBA/CaJ background. We conclude
      that although Cdh23(ahl) homozygosity is necessary, it is not by itself
      sufficient to account for the accelerated hearing loss of C57BL/6J mice.

PMID- 22138312
TI  - Vascular surgery patients prescribed preoperative beta-blockers experienced a
      decrease in the maximal heart rate observed during induction of general
      anesthesia.
AB  - OBJECTIVE: To investigate the association of preoperative beta-blocker usage and
      maximal heart rates observed during the induction of general anesthesia. DESIGN:
      Retrospective descriptive, univariate, and multivariate analyses of electronic
      hospital and anesthesia medical records. SETTING: A tertiary-care medical center
      within the Veterans Health Administration. PARTICIPANTS: Consecutive adult
      elective and emergent patients presenting for vascular surgery during calendar
      years 2005 to 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the
      430 eligible cases, 218 were prescribed beta-blockers, and 212 were not taking
      beta-blockers. The two groups were comparable across baseline patient factors
      (ie, demographic, morphometric, surgical duration, and surgical procedures) and
      induction medication doses. The beta-blocker group experienced a lower maximal
      heart rate during the induction of general anesthesia compared with the non-beta
      blocker group (105 +/- 41 beats/min v 115 +/- 45 beats/min, respectively; p <
      0.01). Adjusted linear regression found a statistically significant association
      between lower maximal heart rate and the use of beta-blockers (beta = -11.1
      beats/min, p < 0.01). There was no difference between groups in total
      intraoperative beta-blocker administration. CONCLUSIONS: Preoperative beta
      blockade of vascular surgery patients undergoing general anesthesia is associated
      with a lower maximal heart rate during anesthetic induction. There may be
      potential benefits in administering beta-blockers to reduce physiologic stress in
      this surgical population at risk for perioperative cardiac morbidity. Future
      research should further explore intraoperative hemodynamic effects in light of
      existing practice guidelines for optimal medication selection, dosage, and heart
      rate control.

PMID- 22138313
TI  - Timing of preoperative aspirin discontinuation and outcome after elective
      coronary artery bypass graft surgery.
AB  - OBJECTIVE: Whether aspirin should be discontinued before coronary artery bypass
      grafting is controversial. The potential benefits and harms associated with late
      use of aspirin (no discontinuation or discontinuation <3 days before surgery)
      were investigated in this retrospective, multicenter study. DESIGN:
      Retrospective, multicenter study. SETTING: Two university hospitals and one
      central hospital. PARTICIPANTS: A consecutive series of 859 patients who
      underwent elective coronary artery bypass grafting from January 2008 through
      December 2010. INTERVENTIONS: Aspirin (100 mg/day) was used <3 days before
      surgery in 240 patients and was discontinued >3 days before surgery in 619
      patients. RESULTS: In the overall series, similar in-hospital mortality, amount
      of postoperative blood loss, rate of re-exploration for excessive bleeding, and
      use of blood products were observed in the study groups. However, aspirin
      discontinuation >3 days before surgery tended to be associated with a higher
      postoperative stroke rate (1.9% v 0.4%, p = 0.13). Such a trend was observed
      after off-pump (1.9% v 0%, p = 0.58) and on-pump (2.0% v 0.6%, p = 0.46) surgery.
      Among 153 pairs matched by the propensity score, patients with aspirin
      discontinued >3 days before surgery had a significantly higher rate of
      postoperative stroke (5.9% v 0.7%, p = 0.02) and tended to have a higher risk of
      the composite adverse outcome endpoint (19.6% v 12.4%, p = 0.09). The
      postoperative release of troponin I was similar in the study groups. CONCLUSIONS:
      Late or no discontinuation of low-dose aspirin before coronary artery bypass
      grafting may decrease the risk of postoperative stroke without increased
      postoperative bleeding and need for blood transfusion. These findings and the
      risk of cardiovascular events possibly occurring at the time of its
      discontinuation suggest that the use of aspirin until the day of elective
      coronary surgery may be beneficial.

PMID- 22138315
TI  - Mitochondria: commanders of innate immunity and disease?
AB  - Mitochondrial dysfunction is associated with the manifestation and origin of a
      plethora of diseases and disorders. Whilst classically the role of these
      archetypical 'powerhouses' in many disease phenotypes has been attributed to
      their ability to regulate cell metabolism and cell death pathways, emerging data
      posit that mitochondria may also act as powerful initiators and masters of the
      innate immune response. This new paradigm complements the current mitochondrial
      dogma, whereby molecules endogenously present on or inside the mitochondria may
      act as immune regulators in response to stress or pathogens and may also be
      responsible for the initiation and/or manifestation of chronic inflammation
      observed in many diseases and disorders.

PMID- 22138314
TI  - The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen
      presentation pathway.
AB  - HLA-DM serves a critical function in the loading and editing of peptides on MHC
      class II (MHCII) molecules. Recent data showed that the interaction cycle between
      MHCII molecules and HLA-DM is dependent on the occupancy state of the peptide
      binding groove. Empty MHCII molecules form stable complexes with HLA-DM, which
      are disrupted by binding of high-affinity peptide. Interestingly, MHCII molecules
      with fully engaged peptides cannot interact with HLA-DM, and prior dissociation
      of the peptide N-terminus from the groove is required for HLA-DM binding. There
      are significant similarities to the peptide loading process for MHC class I
      molecules, even though it is executed by a distinct set of proteins in a
      different cellular compartment.

PMID- 22138316
TI  - Impact of delayed processing of bovine peripheral blood on differential gene
      expression.
AB  - RT-qPCR can be used to accurately determine expression levels of genes following
      RNA extraction from tissue samples. If blood is the source of total RNA, it is
      often desirable to process the samples immediately following collection because
      delays in processing for RNA extraction may influence mRNA expression estimates
      obtained from RT-qPCR analyses. However, this may not be feasible if the site of
      blood collection is distant from the processing laboratory. In the present study,
      the effects of delays in the processing of blood samples on mRNA expression data
      was investigated using a panel of 23 functionally diverse genes from five
      different gene ontology (GO) categories in peripheral blood sampled from ten age
      matched healthy cattle. Venous blood was collected in TempusTM Blood RNA tubes,
      which contain reagents that lyse blood cells immediately and stabilise the RNA
      signature (T(0)). Blood was also collected in conventional lithium heparin
      collection tubes, and stored at ambient temperature for T(4), T(6) and T(8)h,
      prior to total RNA extraction. The mRNA expression profiles of these 23 genes
      were determined by RT-qPCR and compared across the time course. Thirteen genes
      showed significant up- or down-fold changes in mRNA expression over the 8h time
      course. Among the GO categories, genes in the Immune response category showed the
      most differential expression. These results also demonstrated that the changes in
      mRNA expression for the IFNG gene, which encodes the cytokine IFN-gamma, did not
      correspond to IFN-gamma protein levels estimated using ELISA.

PMID- 22138317
TI  - Letter to the editor--average T-wave alternans in ambulatory electrocardiogram
      recordings in patients with heart failure.

PMID- 22138318
TI  - Measuring children's decision-making involvement regarding chronic illness
      management.
AB  - OBJECTIVES: To develop a measure of decision-making involvement in children and
      adolescents with cystic fibrosis, diabetes, and asthma. METHODS: Parent-child
      dyads completed the Decision-Making Involvement Scale (DMIS) and measures of
      locus of control and family communication. DMIS items were subjected to
      exploratory and confirmatory factor analysis (CFA). Temporal stability and
      construct validity were assessed. RESULTS: The parent form was reduced to 20
      items representing five factors. CFA showed that the five factors were an
      acceptable fit to the parent- and child-report data. Internal consistency values
      ranged from 0.71 to 0.91. Temporal stability was supported by moderate
      substantial intraclass correlation coefficients. DMIS subscales were associated
      with child age, child locus of control, and family communication. CONCLUSIONS:
      The DMIS can be used to inform our understanding of the transition to greater
      independence for illness management. Additional research is needed to examine
      outcomes of decision-making involvement, including treatment adherence and
      responsibility.

PMID- 22138319
TI  - The estimation of premorbid intelligence levels among Portuguese speakers: the
      Irregular Word Reading Test (TeLPI).
AB  - Information regarding cognitive abilities in earlier stages of life is essential
      to ascertain if and to what extent these may have declined. When unavailable,
      clinicians rely on estimate methods. One of the contemporary methods used
      worldwide combines performance on irregular word reading test with demographics
      since it has shown to provide reliable estimates of premorbid ability. Hence, a
      reading test portuguese irregular word reading test (TeLPI) was developed,
      filling an important gap in the neuropsychological evaluation of Portuguese
      speakers. Using 46 irregular, infrequent Portuguese words, TeLPI was validated
      against Wechsler Adult Intelligence Scale (WAIS)-III (N = 124), and regression
      based equations were determined to estimate premorbid IQ considering TeLPI scores
      and demographic variables. TeLPI scores accounted for 63% of the variance of WAIS
      III Full-Scale IQ, 62% of Verbal IQ, and 47% of Performance IQ and thus were
      considered valid for premorbid intelligence estimation.

PMID- 22138320
TI  - Immediate list recall as a measure of short-term episodic memory: insights from
      the serial position effect and item response theory.
AB  - The serial position effect shows that two interrelated cognitive processes
      underlie immediate recall of a supraspan word list. The current study used item
      response theory (IRT) methods to determine whether the serial position effect
      poses a threat to the construct validity of immediate list recall as a measure of
      verbal episodic memory. Archival data were obtained from a national sample of
      4,212 volunteers aged 28-84 in the Midlife Development in the United States
      study. Telephone assessment yielded item-level data for a single immediate recall
      trial of the Rey Auditory Verbal Learning Test (RAVLT). Two parameter logistic
      IRT procedures were used to estimate item parameters and the Q(1) statistic was
      used to evaluate item fit. A two-dimensional model better fit the data than a
      unidimensional model, supporting the notion that list recall is influenced by two
      underlying cognitive processes. IRT analyses revealed that 4 of the 15 RAVLT
      items (1, 12, 14, and 15) were misfit (p < .05). Item characteristic curves for
      items 14 and 15 decreased monotonically, implying an inverse relationship between
      the ability level and the probability of recall. Elimination of the four misfit
      items provided better fit to the data and met necessary IRT assumptions.
      Performance on a supraspan list learning test is influenced by multiple cognitive
      abilities; failure to account for the serial position of words decreases the
      construct validity of the test as a measure of episodic memory and may provide
      misleading results. IRT methods can ameliorate these problems and improve
      construct validity.

PMID- 22138321
TI  - Structural characterization of linear isomalto-/malto-oligomer products
      synthesized by the novel GTFB 4,6-alpha-glucanotransferase enzyme from
      Lactobacillus reuteri 121.
AB  - Recently, a novel glucansucrase (GS)-like gene (gtfB) was isolated from the
      probiotic bacterium Lactobacillus reuteri 121 and expressed in Escherichia coli.
      The purified recombinant GTFB enzyme was characterized and turned out to be
      inactive with sucrose, the natural GS substrate. Instead, GTFB acted on malto
      oligosaccharides (MOSs), thereby yielding elongated gluco-oligomers/polymers
      containing besides (alpha1 -> 4) also (alpha1 -> 6) glycosidic linkages, and it
      was classified as a 4,6-alpha-glucanotransferase. To gain more insight into its
      reaction specificity, incubations of the GTFB enzyme with a series of MOSs and
      their corresponding alditols [degree of polymerization, DP2(-ol)-DP7(-ol)] were
      carried out, and (purified) products were structurally analyzed with matrix
      assisted laser desorption ionization time-of-flight mass spectrometry and one
      /two-dimensional (1)H and (13)C nuclear magnetic resonance spectroscopy. With
      each of the tested malto-oligomers, the GTFB enzyme yielded series of novel
      linear isomalto-/malto-oligomers, in the case of DP7 up to DP >35.

PMID- 22138322
TI  - Semantic similarity analysis of protein data: assessment with biological features
      and issues.
AB  - The integration of proteomics data with biological knowledge is a recent trend in
      bioinformatics. A lot of biological information is available and is spread on
      different sources and encoded in different ontologies (e.g. Gene Ontology).
      Annotating existing protein data with biological information may enable the use
      (and the development) of algorithms that use biological ontologies as framework
      to mine annotated data. Recently many methodologies and algorithms that use
      ontologies to extract knowledge from data, as well as to analyse ontologies
      themselves have been proposed and applied to other fields. Conversely, the use of
      such annotations for the analysis of protein data is a relatively novel research
      area that is currently becoming more and more central in research. Existing
      approaches span from the definition of the similarity among genes and proteins on
      the basis of the annotating terms, to the definition of novel algorithms that use
      such similarities for mining protein data on a proteome-wide scale. This work,
      after the definition of main concept of such analysis, presents a systematic
      discussion and comparison of main approaches. Finally, remaining challenges, as
      well as possible future directions of research are presented.

PMID- 22138323
TI  - A review of statistical methods for prediction of proteolytic cleavage.
AB  - A fundamental component of systems biology, proteolytic cleavage is involved in
      nearly all aspects of cellular activities: from gene regulation to cell lifecycle
      regulation. Current sequencing technologies have made it possible to compile
      large amount of cleavage data and brought greater understanding of the underlying
      protein interactions. However, the practical impossibility to exhaustively
      retrieve substrate sequences through experimentation alone has long highlighted
      the need for efficient computational prediction methods. Such methods must be
      able to quickly mark substrate candidates and putative cleavage sites for further
      analysis. Available methods and expected reliability depend heavily on the type
      and complexity of proteolytic action, as well as the availability of well
      labelled experimental data sets: factors varying greatly across enzyme families.
      For this review, we chose to give a quick overview of the general issues and
      challenges in cleavage prediction methods followed by a more in-depth
      presentation of major techniques and implementations, with a focus on two
      particular families of cysteine proteases: caspases and calpains. Through their
      respective differences in proteolytic specificity (high for caspases, broader for
      calpains) and data availability (much lower for calpains), we aimed to illustrate
      the strengths and limitations of techniques ranging from position-based matrices
      and decision trees to more flexible machine-learning methods such as hidden
      Markov models and Support Vector Machines. In addition to a technical overview
      for each family of algorithms, we tried to provide elements of evaluation and
      performance comparison across methods.

PMID- 22138324
TI  - Functional mapping of ontogeny in flowering plants.
AB  - All organisms face the problem of how to perform a sequence of developmental
      changes and transitions during ontogeny. We revise functional mapping, a
      statistical model originally derived to map genes that determine developmental
      dynamics, to take into account the entire process of ontogenetic growth from
      embryo to adult and from the vegetative to reproductive phase. The revised model
      provides a framework that reconciles the genetic architecture of development at
      different stages and elucidates a comprehensive picture of the genetic control
      mechanisms of growth that change gradually from a simple to a more complex level.
      We use an annual flowering plant, as an example, to demonstrate our model by
      which to map genes and their interactions involved in embryo and postembryonic
      growth. The model provides a useful tool to study the genetic control of
      ontogenetic growth in flowering plants and any other organisms through proper
      modifications based on their biological characteristics.

PMID- 22138325
TI  - Epistatic effects between variants of kappa-opioid receptor gene and A118G of mu
      opioid receptor gene increase susceptibility to addiction in Indian population.
AB  - OBJECTIVE: Unequivocal evidence suggests contribution of kappa-opioid receptor
      (KOR) in addiction to drugs of abuse. A study was undertaken to identify the
      single nucleotide polymorphisms (SNP) at selective areas of kappa opioid receptor
      1 (OPRK1) gene in heroin as well as in alcohol addicts and to compare them with
      that in control population. The potential interaction of the identified KOR SNPs
      with A118G of MU opioid receptor was also investigated. METHODS: Two hundred
      control subjects, one hundred thirty heroin and one hundred ten alcohol addicts,
      all male and residing in Kolkata, a city in eastern India, volunteered for the
      study. Exons 3 and 4 of OPRK1 and the SNP, A118G of mu opioid receptor 1 (OPRM1)
      in the DNA samples were genotyped by sequencing and restriction fragment length
      polymorphism respectively. The SNPs identified in the population were analyzed by
      odds ratio and its corresponding 95% confidence interval was estimated using
      logistic regression models. SNP-SNP interactions were also investigated. RESULTS:
      Three SNPs of OPRK1, rs16918875, rs702764 and rs963549, were identified in the
      population, none of which showed significant association with addiction. On the
      other hand, significant association was observed for A118G with heroin addiction
      (chi2=7.268, P=0.0264) as well as with alcoholic addition (chi2=6.626, P=0.0364).
      A potential SNP-SNP interaction showed that the odds of being addicted was 2.51
      fold in heroin subjects [CI (95%)=1.1524 to 5.4947, P=0.0206] and 2.31 fold in
      alcoholics [CI (95%)=1.025 to 5.24, P=0.0433] with the OPRK1 (rs16918875) and
      A118G risk alleles than without either. A significant interaction was also
      identified between GG/AG of A118G and GG of rs702764 [O.R (95%)=2.04 (1.279 to
      3.287), P=0.0029] in case of opioid population. CONCLUSION: Our study suggests
      that set associations of polymorphisms may be important in determining the risk
      profile for complex diseases such as addiction.

PMID- 22138326
TI  - The association of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5
      HTTVNTR gene polymorphisms and antisocial personality disorder in male heroin
      dependent Chinese subjects.
AB  - OBJECTIVE: To explore the association between the 5-HTR2A-1438A/G, COMTVal158Met,
      MAOA-LPR, DATVNTR and 5-HTTVNTR polymorphisms with comorbidity of antisocial
      personality disorder in male heroin-dependent patients. SUBJECTS AND METHODS: In
      case control study, we compared the polymorphic distributions of 5-HTR2A-1438A/G,
      COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR in 588 male heroin-dependent
      patients (including 311 patients with antisocial personality disorder and 277
      patients without antisocial personality disorder) and 194 normal males by
      genotypes, alleles, and interaction between genes. RESULTS: Between male heroin
      dependent patients with antisocial personality disorder and normal males, and
      between male heroin-dependent patients with and without antisocial personality
      disorder, the distributions of 5-HTTVNTR polymorphic genotypes and alleles were
      in statistical significance. Individuals carrying 10R allele were in higher risk
      of the comorbidity of antisocial personality disorder and heroin dependence. By
      MDR analyses, the interaction between 5-HTTVNTR and DATVNTR was close to
      statistical significance in predicting the risk of antisocial personality
      disorder in male heroin dependent patients. In male heroin dependent patients,
      individuals carrying 5-HTTVNTR 10R allele or/and DATVNTR 9R allele were in higher
      risks of co-occurring antisocial personality disorder, while individuals with 5
      HTTVNTR 12R/12R and DATVNTR 10R/10R genotypes together were in lower risks of
      antisocial personality disorder. CONCLUSION: 5-HTTVNTR, and the interaction
      between 5-HTTVNTR and DATVNTR may be associated with the comorbidity of
      antisocial personality disorder in male heroin-dependent patients.

PMID- 22138327
TI  - Differential effects of progesterone and medroxyprogesterone on delay eyeblink
      conditioning in ovariectomized rats.
AB  - Ovarian hormones modulate acquisition processes involved in classical
      conditioning. Although progesterone has been indirectly implicated, its role in
      classical conditioning of the eyeblink response has not been directly
      investigated. We assessed the effects of daily dosing of progesterone or
      medroxyprogesterone (MPA), a non-metabolized synthetic progestin, upon the
      acquisition of a classically conditioned eyeblink response in ovariectomized
      (OVX) female rats. Rats were dosed 4h prior to each training session with 0.1 or
      1.5 mg/kg of either of these hormones or sesame oil. A delay conditioning
      paradigm was employed using a 500 ms conditioned stimulus coterminating with a 10
      ms 10 V unconditioned stimulus. At the low dose, progesterone and MPA rats did
      differ from each other, with MPA-treated rats learning slower, but neither group
      differed from OVX-oil or Sham-oil controls. No group differences in acquisition
      were observed at the higher dose. During extinction trials, high-dose MPA
      treatment and OVX-oil groups extinguished quicker than the high-dose progesterone
      treated group. In addition, unconditional response (UR) amplitudes were lower in
      all OVX groups, regardless of hormone or oil treatment, compared to the sham-oil
      group. Since MPA did not affect extinction, it is likely the slower extinction in
      the progesterone-treated rats is due to a metabolite of progesterone.
      Corticosterone is discussed as a likely candidate for such a role. In addition,
      we found chronic absence of ovarian hormones decreased UR amplitudes, although
      differences in UR amplitudes were not associated with changes in the acquisition
      process. These results are discussed with respect to differences in the hormonal
      effects upon acquisition versus extinction processes and how these data may
      explain reports of learning differences in women based on oral contraceptive
      usage.

PMID- 22138328
TI  - Comment on: Micronutrient status in morbidly obese females prior to bariartic
      surgery.

PMID- 22138329
TI  - Weighing the evidence for an association between obesity and suicide risk.
AB  - Chronic illness is an important risk factor for suicidal behavior. Obesity is
      perhaps the most prevalent chronic disease at present, although the contribution
      of obesity to fatal and nonfatal suicide is controversial. Several large
      population-based studies have shown that obesity is independently linked to an
      increased risk of suicide. However, this association has been challenged by
      reports demonstrating a paradoxical relationship between an increasing body mass
      index and suicide. Recently, it has also been suggested that bariatric surgery
      patients are at increased risk of death by suicide postoperatively. We reviewed
      the heterogeneous data concerning the relationship between obesity and suicide.
      We also critically examined recent reports describing the incidence of fatal
      suicide events after bariatric surgery. From the present review, it appears that
      a positive association between obesity and suicide has been observed more
      frequently than a negative or absent association. This implies that obese
      individuals are indeed at an increased risk of suicide. This risk seems to
      persist despite treatment of obesity with bariatric surgery.

PMID- 22138330
TI  - Relationship of bypassed limb length and remission of type 2 diabetes mellitus
      after Roux-en-Y gastric bypass.

PMID- 22138331
TI  - Evaluation of nurses' attitudes toward adult obese patients: erratum.

PMID- 22138332
TI  - Fistulation of adjustable gastric band tube into small bowel.

PMID- 22138333
TI  - Necdin-E2F4 interaction provides insulin-sensitizing effect after weight loss
      induced by gastric bypass surgery.
AB  - BACKGROUND: The insulin-like growth factor-1 (IGF-1) signaling pathway promotes
      adipocyte differentiation and, therefore, insulin sensitivity by suppression of
      necdin expression, which represses peroxisome proliferator-activated receptor
      gamma promoter activity by interaction with E2F4 in mouse adipocytes. The aim of
      the present study was to test the hypothesis that this pathway represents one of
      the mechanisms by which Roux-en-Y gastric bypass surgery (RYGB) induces
      resolution of insulin resistance. METHODS: Clinical samples were collected and
      the key biomarkers measured to test the hypothesis that the IGF-1 pathway
      represents 1 of the mechanisms by which RYGB induces resolution of insulin
      resistance in obese individuals. RESULTS: Free IGF-1 levels were significantly
      greater in the post-RYGB patients than in the pre-RYGB obese patients (2.55 +/-
      1.54 versus 1.32 +/- .65 MUg/L, P = .03) and similar to that in normal weight
      controls (2.54 +/- 1.27 MUg/L). Necdin and E2F4 gene expression in the adipose
      tissue was significantly downregulated after RYGB compared with obese and were
      similar to the levels observed in the controls. In mature human adipocytes
      cultured in vitro, treatment with des-IGF-1 induced downregulation of necdin and
      E2F4 gene expression in a dose-dependent manner (P = .01). CONCLUSION: After
      RYGB, the insulin/IGF-1 signaling pathway is activated and could account for the
      observed decrease in the expression of necdin, which represses peroxisome
      proliferator-activated receptor-gamma promoter activity by interaction with E2F4.
      This could represent one of the mechanisms that induce resolution of insulin
      resistance after RYGB.

PMID- 22138334
TI  - Five hepatopancreatic and one epidermal chitinases from a pandalid shrimp
      (Pandalopsis japonica): cloning and effects of eyestalk ablation on gene
      expression.
AB  - Six cDNAs encoding chitinase proteins in Pandalopsis japonica were isolated by
      using polymerase chain reaction (PCR) cloning methods and bioinformatic analysis
      of expressed sequence tags (ESTs). The cDNAs, designated Pj-Cht1, 2, 3A, 3B, 3C,
      and 4, encoded proteins ranging from 388 to 607 amino acid residues in length
      (43.61-67.62kDa) and displayed a common structural organization: an N-terminal
      catalytic domain, a Thr/Pro-rich linker region, and either 0 (Pj-Cht2, 3A), 1 (Pj
      Cht1, 3B, and 3C), or 2 (Pj-Cht4) C-terminal chitin-binding domain(s) (CBD). Pj
      Cht1 and 2 lacked the 5' end of the open reading frame (ORF); the other Pj-Chts
      contained the complete ORF. All known decapod crustacean chitinases were
      segregated into at least four groups based on phylogenetic analysis and domain
      organization. Group 1 chitinases, represented by Pj-Cht1, were most closely
      related to insect group I chitinases and may function in the digestion of the
      peritrophic membrane. Group 2 chitinases including Pj-Cht2 show different domain
      organizations and pI value from other chitinases and appear to function in
      degradation of the old exoskeleton during the premolt period. Group 3 chitinases,
      represented by Pj-Cht3A, 3B, and 3C, may function in digestion of chitin
      containing food and defense against pathogens. Group 4 chitinases, represented by
      Pj-Cht4, have two CBDs and their functions are unknown. Five Pj-Chts (Pj-Cht1,
      3A, 3B, 3C, and 4) are expressed in the hepatopancreas and intestine, whereas Pj
      Cht2 is expressed in epidermis and SG/XO complex suggesting crustacean chitinases
      can be classified into two groups (hepatopancreatic and epidermal) based on the
      expression profile. Eyestalk ablation (ESA) down-regulated the hepatopancreatic
      chitinase expression (Pj-Cht1, 3A, and 3C); Pj-Cht3B expression was not
      significantly affected by ESA. By contrast, mRNA levels of Pj-Cht2 were
      significantly upregulated in 7days post-ESA. Pj-Cht4 mRNA levels were too low for
      measurement with quantitative polymerase chain reaction. ESA had no significant
      effect on chitinase expression in the intestine. These data indicate that Pj
      Cht1, 3A, 3B, 3C, and 4 are hepatopancreatic chitinases that may function in the
      digestion of ingested chitin and the modification of peritrophic membrane in the
      intestine. By contrast, epidermal chitinase, Pj-Cht2 may play a role in chitin
      metabolism during molt cycle as shown in other crustacean group 2 chitinases.

PMID- 22138335
TI  - Bottom-up guidance to grouped items in conjunction search: evidence for color
      grouping.
AB  - Previous studies have demonstrated that observers can search through a subset of
      items carrying a minority feature to find a conjunction target (Sobel & Cave,
      2002). We examined whether subset search takes place when participants have less
      specific foreknowledge of the target (when the target is one of two possible
      items), measuring eye movements as well as reaction times. When there were
      unequal ratios of distractors, fixations were initially directed to the small
      subset. These initial eye movements were often directed between items with the
      same feature, suggesting guidance from pooled feature values. There was stronger
      guidance within color- than orientation-defined groups, although the features
      were balanced for salience. The results suggest that grouping of items by color
      operates more globally than grouping in orientation.

PMID- 22138336
TI  - Multi-linear regression analysis, preliminary biotic ligand modeling, and cross
      species comparison of the effects of water chemistry on chronic lead toxicity in
      invertebrates.
AB  - The current study examined the chronic toxicity of lead (Pb) to three
      invertebrate species: the cladoceran Ceriodaphnia dubia, the snail Lymnaea
      stagnalis and the rotifer Philodina rapida. The test media consisted of natural
      waters from across North America, varying in pertinent water chemistry parameters
      including dissolved organic carbon (DOC), calcium, pH and total CO(2). Chronic
      toxicity was assessed using reproductive endpoints for C. dubia and P. rapida
      while growth was assessed for L. stagnalis, with chronic toxicity varying
      markedly according to water chemistry. A multi-linear regression (MLR) approach
      was used to identify the relative importance of individual water chemistry
      components in predicting chronic Pb toxicity for each species. DOC was an
      integral component of MLR models for C. dubia and L. stagnalis, but surprisingly
      had no predictive impact on chronic Pb toxicity for P. rapida. Furthermore,
      sodium and total CO(2) were also identified as important factors affecting C.
      dubia toxicity; no other factors were predictive for L. stagnalis. The Pb
      toxicity of P. rapida was predicted by calcium and pH. The predictive power of
      the C. dubia and L. stagnalis MLR models was generally similar to that of the
      current C. dubia BLM, with R(2) values of 0.55 and 0.82 for the respective MLR
      models, compared to 0.45 and 0.79 for the respective BLMs. In contrast the BLM
      poorly predicted P. rapida toxicity (R(2)=0.19), as compared to the MLR
      (R(2)=0.92). The cross species variability in the effects of water chemistry,
      especially with respect to rotifers, suggests that cross species modeling of
      invertebrate chronic Pb toxicity using a C. dubia model may not always be
      appropriate.

PMID- 22138337
TI  - As(III) retention kinetics, equilibrium and redox stability on biosynthesized
      schwertmannite and its fate and control on schwertmannite stability on acidic (pH
      3.0) aqueous exposure.
AB  - High As(III) enrichment in schwertmannite precipitated acid mine impacted areas
      is a major concern considering its acute toxicity and mobility where the current
      knowledge of their interaction, redox conditions and schwertmannite metastability
      is inadequate. In this study we have investigated such aspects through batch
      isotherm, microscopic and spectroscopic techniques. Schwertmannite produced by
      biotic process with 14.7 m(2)g(-1) surface area demonstrated a rapid As(III)
      uptake followed by slow retention possibly into the internal absorbing sites
      through multilayer and heterogeneous sorption processes. Chemical, X-ray
      diffraction, infrared and microscopic examinations revealed that ionic exchange
      between schwertmannite SO(4)(2-) and As(III) and surface precipitation governed
      the total As(III) uptake where lower dissolved SO(4)(2-) and high sorbent mass
      enhanced As(III) retention. Redox instability of sorbed As(III) was evidenced
      from the near-edge spectroscopic analysis at extremely high Fe(III):As(III) ratio
      (5.5*10(5)) leading to surface oxidation to As(V), while As(III) was found as the
      predominant redox species at high As(III):Fe(III) ratios. Only 0.83% of sorbed
      As(III) was released which was subsequently re-adsorbed into schwertmannite
      during 4 months stabilization without any evidence of mineralogical
      transformation.

PMID- 22138338
TI  - Zamzam water: concentration of trace elements and other characteristics.
AB  - Many Muslims drink Zamzam water for use either medicinally or religiously.
      Millions of pilgrims drink it and take bottles of it to their home countries.
      Heated scientific and political debates appeared after BBC reported in May 2011
      that Zamzam water is poisonous, because of the high levels of arsenic. The World
      Health Organizations classifies arsenic as a human carcinogen, but some types of
      arsenic are also used as medicines. Adequate scientific studies on the Zamzam
      water are absent. This paper will provide, for the first time, basic and
      comprehensive information regarding the geochemical properties of Zamzam water
      for more than 30 indicators and using the state-of-the-art laboratory facilities.
      The data will help us to understand the sources of pollution under discussion,
      reactions at both local and international levels; and will highlight the
      potential healing capacity of Zamzam water. Thirty Zamzam water samples were
      collected by three distinct methods; from 10 pilgrims living in different
      locations in Germany in 2007, 10 samples from shops in Frankfurt and Berlin in
      2011, and 10 samples directly from Makkah in 2011. The samples were analyzed 2
      weeks after collection for more than 30 indicators: pH, EC, Eh, Cl, F, Br, NO(3),
      PO(4), SO(4), HCO(3), Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni,
      Pb, Sr, and Zn beside others. Four major instruments were used; the IC, the
      ICPOES, the ICPMS and the HGAAS. The quality of the water did not change for 2
      years and there was an excellent agreement among the results of the 30 water
      samples as well as between the results of the 2 years for the same samples
      analyzed in 2007 and 2008. The water is alkaline (average pH is 8) with an
      average Li concentration of 15 MUg L(-1). The average concentrations of As and
      NO(3) showed values three times higher than the WHO standards (27 MUg L(-1) and
      150 mg L(-1), respectively). The averages of Ca and K were 95 and 50 mg L(-1),
      respectively. Very urgent steps are required to scientifically screen for the
      elevated parameters As, NO(3), Ca, and K in all Zamzam water sources and
      locations with full transparency. The resultant information should be made
      available to the public, and the relationship between pollution and human health
      should be addressed. The alkalinity of Zamzam water and the presence of trace
      amounts of As and Li may cause the healing power. However, a scientific strategy
      should be developed and adopted to enable further research and studies on
      toxicology and treatment technologies could be applied if needed.

PMID- 22138339
TI  - Application of a novel open-source program for measuring the effects of toxicants
      on the swimming behavior of large groups of unmarked fish.
AB  - The aim of this study was to demonstrate a novel method for measuring the effects
      of toxicants on the behavior of groups of unmarked fish. Ctrax is an open source
      Python-based machine vision program that was originally designed to track fruit
      flies (Drosophila). The effects of the fish anaesthetic quinaldine sulfate on the
      behavior of groups of 10 unmarked Arabian killifish (Aphanias dispar) in a small
      arena were measured. Ctrax was able to identify and track the X-Y coordinates of
      the individual fish over 1 min recording periods. The data was analyzed using
      specifically written Matlab (The MathworksTM) toolboxes and the effects of
      quinaldine sulfate on absolute swimming velocity, forward swimming velocity, rate
      of change in orientation and distance to wall were calculated. Additionally the
      effects of quinaldine sulfate on path tortuosity were also measured. Ctrax has
      significant benefits over other available technologies for tracking the 2
      dimensional coordinates of fish. In particular the software is open source and
      thus freely available, it is accurate, requires only simple easily available
      equipment and able to track potentially large groups of fish (possibly >50) while
      maintaining their individual identities.

PMID- 22138340
TI  - Influence of inorganic anions on metals release from oil sands coke and on
      toxicity of nickel and vanadium to Ceriodaphnia dubia.
AB  - In a previous study it was shown that pH significantly influences the release of
      metals from oil sands coke, particularly Ni and V which were identified as the
      cause of coke leachate toxicity. Coke comes in contact with oil sands process
      water (OSPW) during its transport to and long term storage in reclamation
      landscapes. However, the influence of dominant inorganic anions present in OSPW
      (i.e. HCO(3)(-), Cl(-) and SO(4)(2-)) on metals release from coke and on
      speciation and toxicity of Ni and V, has not been characterized before. Coke was
      subjected to a 15-d batch leaching process at four levels of HCO(3)(-), Cl(-) and
      SO(4)(2-) to determine the influence on metals release and speciation. Further,
      the effects of each of the three anions on Ni and V toxicity, as well as the
      mixture toxicity of Ni and V, were assessed using the three-brood Ceriodaphnia
      dubia test. Inorganic anions had a significant influence on the type and amount
      of metals released from coke. Specifically, sulfate increased the mobilization of
      cationic metals (e.g. Ni, Fe, Mn and Zn), whereas bicarbonate enhanced the
      release of oxyanion forming metals (e.g. Al, As, Mo and V) from coke. Chloride
      had no particular effect on the type and amount of metals released. With respect
      to toxicity, elevated bicarbonate levels decreased the 7-d Ni IC50 from 6.3 to
      2.3 MUg L(-1), whereas sulfate showed an ameliorative effect against V toxicity
      to C. dubia. In combination, Ni and V acted additively at their highest sub
      lethal concentrations. Aqueous chemistry and toxicity of Ni and V are discussed
      with the goal of informing reclamation efforts at the Athabasca oil sands.

PMID- 22138342
TI  - Does FDG PET-assisted management of patients with left ventricular dysfunction
      improve quality of life? A substudy of the PARR-2 trial.
AB  - BACKGROUND: Patients with left ventricular dysfunction whose management is
      directed by F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)
      imaging may have a quality of life (QOL) benefit over standard care. METHODS:
      Among 430 patients randomized in the PET and Recovery Following Revascularization
      (PARR)-2 trial to FDG PET-assisted management vs standard, QOL scores were
      obtained using the European Quality of Life-5 Dimensions (EQ-5D) in 427 patients
      at baseline (FDG PET n = 216; standard n = 211) and 355 patients at 12-month
      follow-up (FDG PET n = 184; standard n = 171). EQ-5D scores between FDG PET and
      standard arms were compared using mixed model repeated measures (MMRM). Subgroup
      analysis compared EQ-5D scores between patients in FDG PET who adhered to PET
      recommendations (Adherence) vs standard using MMRM. Interaction of
      revascularization with management was assessed using a general linear model.
      RESULTS: A trend toward higher EQ-5D scores in FDG PET was observed (P = 0.056).
      Subgroup analysis showed a significant difference favouring adherence (P = 0.04).
      Higher QOL at 6 months for FDG PET (P = 0.02) and Adherence (P = 0.02) were
      observed. For revascularization, an interaction with management (FDG PET vs
      standard) for QOL was observed (6 months: P = 0.01; 12 months: P = 0.1);
      Adherence (6 months: P = 0.01; 12 months: P = 0.1). CONCLUSIONS: FDG PET-directed
      management improves QOL, at least in the short-term and with adherence to
      recommendations. This may relate to revascularization, and may indicate better
      treatment selection using FDG PET.

PMID- 22138343
TI  - Structural studies of intermediates along the cyclization pathway of Aplysia ADP
      ribosyl cyclase.
AB  - Cyclic ADP-ribose (cADPR) is a calcium messenger that can mobilize intracellular
      Ca2+ stores and activate Ca2+ influx to regulate a wide range of physiological
      processes. Aplysia cyclase is the first member of the ADP-ribosyl cyclases
      identified to catalyze the cyclization of NAD+ into cADPR. The catalysis involves
      a two-step reaction, the elimination of the nicotinamide ring and the cyclization
      of the intermediate resulting in the covalent attachment of the purine ring to
      the terminal ribose. Aplysia cyclase exhibits a high degree of leniency towards
      the purine base of its substrate, and the cyclization reaction takes place at
      either the N1- or the N7-position of the purine ring. To decipher the mechanism
      of cyclization in Aplysia cyclase, we used a crystallization setup with multiple
      Aplysia cyclase molecules present in the asymmetric unit. With the use of natural
      substrates and analogs, not only were we able to capture multiple snapshots
      during enzyme catalysis resulting in either N1 or N7 linkage of the purine ring
      to the terminal ribose, we were also able to observe, for the first time, the
      cyclized products of both N1 and N7 cyclization bound in the active site of
      Aplysia cyclase.

PMID- 22138344
TI  - Salt bridges regulate both dimer formation and monomeric flexibility in HdeB and
      may have a role in periplasmic chaperone function.
AB  - Escherichia coli and Gram-negative bacteria that live in the human gut must be
      able to tolerate rapid and large changes in environmental pH. Low pH irreversibly
      denatures and precipitates many bacterial proteins. While cytoplasmic proteins
      are well buffered against such swings, periplasmic proteins are not. Instead, it
      appears that some bacteria utilize chaperone proteins that stabilize periplasmic
      proteins, preventing their precipitation. Two highly expressed and related
      proteins, HdeA and HdeB, have been identified as acid-activated chaperones. The
      structure of HdeA is known and a mechanism for activation has been proposed. In
      this model, dimeric HdeA dissociates at low pH, and the exposed dimeric interface
      binds exposed hydrophobic surfaces of acid-denatured proteins, preventing their
      irreversible aggregation. We now report the structure and biophysical
      characterization of the HdeB protein. The monomer of HdeB shares a similar
      structure with HdeA, but its dimeric interface is different in composition and
      spatial location. We have used fluorescence to study the behavior of HdeB as pH
      is lowered, and like HdeA, it dissociates to monomers. We have identified one of
      the key intersubunit interactions that controls pH-induced monomerization. Our
      analysis identifies a structural interaction within the HdeB monomer that is
      disrupted as pH is lowered, leading to enhanced structural flexibility.

PMID- 22138345
TI  - Crystal structures of two solute receptors for L-cystine and L-cysteine,
      respectively, of the human pathogen Neisseria gonorrhoeae.
AB  - ATP-binding cassette (ABC) transporters are integral membrane proteins that carry
      a variety of substrates across biological membranes at the expense of ATP. The
      here considered prokaryotic canonical importers consist of three entities: an
      extracellular solute receptor, two membrane-intrinsic proteins forming a
      translocation pathway, and two cytoplasmic ATP-binding subunits. The ngo0372-74
      and ngo2011-14 gene clusters from the human pathogen Neisseria gonorrhoeae were
      predicted by sequence homology as ABC transporters for the uptake of cystine and
      cysteine, respectively, and chosen for structural characterization. The structure
      of the receptor component Ngo0372 was obtained in a ligand-free "open"
      conformation and in a "closed" conformation when co-crystallized with L-cystine.
      Our data provide the first structural information of an L-cystine ABC
      transporter. Dissociation constants of 21 and 33 nM for L-cystine and L
      selenocystine, respectively, were determined by isothermal titration calorimetry.
      In contrast, L-cystathionine and L-djenkolic acid are weak binders, while no
      binding was detectable for S-methyl-L-cysteine. Mutational analysis of two
      residues from the binding pocket, Trp97 and Tyr59, revealed that the latter is
      crucial for L-cystine binding. The structure of the Ngo2014 receptor was obtained
      in closed conformation in complex with co-purified L-cysteine. The protein binds
      L-cysteine with a K(d) of 26 nM. Comparison of the structures of both receptors
      and analysis of the ligand binding sites shed light on the mode of ligand
      recognition and provides insight into the tight binding of both substrates.
      Moreover, since L-cystine limitation leads to reduction in virulence of N.
      gonorrhoeae, Ngo0372 might be suited as target for an antimicrobial vaccine.

PMID- 22138346
TI  - A conserved Glu-Arg salt bridge connects coevolved motifs that define the
      eukaryotic protein kinase fold.
AB  - Eukaryotic protein kinases (EPKs) feature two coevolved structural segments, the
      Activation segment, which starts with the Asp-Phe-Gly (DFG) and ends with the Ala
      Pro-Glu (APE) motifs, and the helical GHI subdomain that comprises alphaG-alphaH
      alphaI helices. Eukaryotic-like kinases have a much shorter Activation segment
      and lack the GHI subdomain. They thus lack the conserved salt bridge interaction
      between the APE Glu and an Arg from the GHI subdomain, a hallmark signature of
      EPKs. Although the conservation of this salt bridge in EPKs is well known and its
      implication in diseases has been illustrated by polymorphism analysis, its
      function has not been carefully studied. In this work, we use murine cAMP
      dependent protein kinase (protein kinase A) as the model enzyme (Glu208 and
      Arg280) to examine the role of these two residues. We showed that Ala replacement
      of either residue caused a 40- to 120-fold decrease in catalytic efficiency of
      the enzyme due to an increase in K(m)(ATP) and a decrease in k(cat). Crystal
      structures, as well as solution studies, also demonstrate that this ion pair
      contributes to the hydrophobic network and stability of the enzyme. We show that
      mutation of either Glu or Arg to Ala renders both mutant proteins less effective
      substrates for upstream kinase phosphoinositide-dependent kinase 1. We propose
      that the Glu208-Arg280 pair serves as a center hub of connectivity between these
      two structurally conserved elements in EPKs. Mutations of either residue disrupt
      communication not only between the two segments but also within the rest of the
      molecule, leading to altered catalytic activity and enzyme regulation.

PMID- 22138347
TI  - De novo biosynthesis of glycosaminoglycans in the extracellular matrix of skin
      studied by matrix-assisted laser desorption/ionization mass spectrometry.
AB  - The self-healing capacity of skin is limited, and medical intervention is often
      unavoidable. Skin may be generated ex vivo from cultured fibroblasts. Because the
      molecular composition of de novo formed skin (mostly collagen and
      glycosaminoglycans [GAGs]) is crucial, analytical methods are required for the
      quality control of tissue-engineered products. Here, we show that matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) of
      fibroblast cultures subsequent to digestion with chondroitinase ABC is a reliable
      and fast method to monitor the GAG content of native and bioengineered skin.
      Furthermore, the supplementation of the fibroblast medium with 13C-labeled
      glucose provides insights into the biosynthesis of GAGs.

PMID- 22138348
TI  - Wound healing and anti-inflammatory activities of the Michauxia L'Herit
      (Campanulaceae) species native to Turkey.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Michauxia species are used for the
      treatment of wounds in Turkish traditional medicine. In the present study, wound
      healing, anti-inflammatory and antioxidant activities of the extracts obtained
      from the root and herb of 5 species of Michauxia collected in different parts of
      Turkey were evaluated. MATERIAL AND METHODS: In vivo incision and excision wound
      models were used in order to assess the wound healing effects of the methanolic
      extracts of the plants. Skin samples were also evaluated histopathologically. In
      vivo inhibitory effect of the extracts on acetic acid-induced increase in
      capillary permeability was studied for the assessment of anti-inflammatory
      activity. TBA (thiobarbituric acid) test, qualitative and quantitative DPPH (2,2
      diphenyl-1-picrylhydrazyl) tests were used to evaluate the antioxidant activity.
      RESULTS: Noteworthy wound healing activity was observed for the ointment
      formulation prepared with 1% Michauxia nuda (root) and Michauxia tchihatchewii
      (herb) extracts. The results of histopathological evaluation supported the
      outcome of incision and excision wound models. Moreover, the Michauxia nuda
      (root) exerted remarkable anti-inflammatory effect. The highest antioxidant
      activity was observed with the ethyl acetate extract of Michauxia tchihatchewii
      herb. CONCLUSION: The experimental study revealed that Michauxia displays
      remarkable wound healing and anti-inflammatory and antioxidant activities.

PMID- 22138349
TI  - Evaluation of an extract of North American ginseng (Panax quinquefolius L.) in
      Candida albicans-infected complement-deficient mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is a widely consumed aromatic herb that
      is purported to have health benefits. Several studies report a beneficial impact
      of ginseng or its derivatives on Candida albicans infection in mice and suggest
      that its immune-modulatory properties contribute to this effect. However, these
      studies generally administered ginseng to experimental animals by injection,
      whereas people typically ingest ginseng. Furthermore, although disseminated
      candiasis is typically a disease of immune-impaired hosts, previous studies have
      generally used immune competent host species in the assessments. MATERIALS AND
      METHODS: We evaluated the efficacy of an ingested extract of ginseng against
      Candida albicans infection in DBA/2J mice, which are highly susceptible to
      Candida albicans infection. A ginseng extract was added to the drinking water for
      two days before and for the remainder of the study after intravenous inoculation
      of mice with Candida albicans. Mice were evaluated for morbidity, mortality,
      Candida albicans titers, and concentrations of inflammatory cytokines and
      chemokines. RESULTS: Ingestion of the ginseng extract did not significantly
      affect overall morbidity or mortality. However, ingestion of the extract was
      associated with significantly lower renal titers of Candida albicans and with
      significantly lower concentrations of some inflammatory cytokines in kidney
      and/or serum. CONCLUSIONS: Assessment of morbidity, mortality, inflammatory
      markers, and renal titers after spontaneous ingestion of ginseng by susceptible
      hosts represents a comprehensive approach to characterizations of therapeutic
      efficacy against infectious agents. Our findings extend previous reports of the
      efficacy of ginseng against Candida albicans by demonstrating significant
      reductions in infectious load and some markers of inflammation in susceptible
      mice. Our data therefore support further assessment of the immune-modulatory
      properties of this widely consumed herb and its components.

PMID- 22138350
TI  - Antidepressant-like effect of the extracted of Kai Xin San, a traditional Chinese
      herbal prescription, is explained by modulation of the central monoaminergic
      neurotransmitter system in mouse.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Kai Xin San (KXS) is a traditional Chinese herbal
      prescription for the treatment of depression-like disorders, anxiety, and
      impairment in learning and memory, however, there is very little scientific data
      concerning the efficacy of this. AIM OF THE STUDY: The present study aimed to
      investigate the antidepressant potential of Kai Xin San and its possible
      mechanisms. MATERIALS AND METHODS: Mouse models of depression including the tail
      suspension test (TST) and the forced swim test (FST) were used to evaluate the
      effects of KXS. A possible mechanism was explored in the tests of antagonism of
      reserpine-induced ptosis, akinesia and hypothermia and 5-HTP induced head-twitch
      response in mice. The contents of monoamine neurotransmitters including
      epinephrine (NE), 5-hydroxytryptamine (5-HT) and dopamine (DA) in mice brain were
      determined by Elisa. Spontaneous motor activities of mice and rotarod test were
      performed to find whether KXS has excitatory or inhibitory actions on the central
      nervous system. RESULTS: The results showed that intragastric administration of
      KXS at 175, 350, 700, 1400 mg/kg/day or fluoxetine at 28 mg/kg/day for 3 days
      significantly reduced the duration of immobility in TST and FST, while it showed
      no effect on the spontaneous motor activity and rotarod performance in mice.
      However, the effect was not dose-dependent. The pre-treatment with KXS or
      fluoxetine for 3 days could elevate the contents of NE, 5-HT and DA in mice brain
      significantly. When the mice were treated with KXS (350 mg/kg, p.o) or
      desipramine (30 mg/kg, p.o) for 7 days, both of them could antagonize reserpine
      induced ptosis, akinesia and hypothermia. The KXS (350 mg/kg) also increased the
      accumulative number of the 5-HTP-induced head twitch response in mice in 20 min
      when KXS at dosages of 175, 350, 700 and 1400 mg/kg/day were performed per os
      (p.o.) during a 1-day, 3-day or 7-day period. CONCLUSIONS: Our results suggested
      that KXS exerts antidepressant-like effect. A possible mechanism, at least in
      part, is via the central monoaminergic neurotransmitter system and 5-HT plays a
      major role.

PMID- 22138351
TI  - Pulpal regeneration and root development after subcutaneous transplantation of
      cryopreserved immature teeth in rats.
AB  - The purpose of this in vivo study was to investigate revascularization and root
      growth after autotransplantation of cryopreserved immature teeth. Immature molar
      teeth were extracted in 4-week-old Wistar rats. In the test group, teeth were
      cryopreserved for 1 week and transplanted subcutaneously to the abdomen. In the
      control group, teeth were transplanted subcutaneously immediately after
      extraction. Material was collected in test and control animals at intervals of 1,
      2, 4 and 10 weeks post-transplantation and histological and microradiographical
      examination was performed. Results showed that during the first weeks after
      transplantation, pulpal repair was similar in both groups although degenerated
      pulpal tissue was replaced slower in cryopreserved teeth and some differences in
      types of hard tissue formation were found between test and control teeth. After
      10 weeks, the differences in the regenerated pulpal tissue between cryopreserved
      and control teeth observed during the first weeks were no longer detectable. No
      root growth was detected microradiographically 10 weeks after transplantation in
      any of the transplanted teeth. The presence of dentin-like tissue in the pulp
      cavity of some autotransplanted cryopreserved teeth, suggests survival of pulpal
      tissue after cryopreservation.

PMID- 22138352
TI  - Movement preparation and cortical processing of afferent inputs in cortical
      tremor: an event-related (de)synchronization (ERD/ERS) study.
AB  - OBJECTIVE: We sought to characterize cortical activity related to motor control
      in patients presenting with isolated cortical tremor, in order to determine
      whether or not myoclonus-related impairments are a source of event-related
      desynchronization/synchronization (ERD/ERS) disruption. METHODS: Nine patients
      presenting with isolated cortical tremor were compared with controls. Mu and beta
      ERD/ERS were computed over the scalp and brain surfaces using 128-channel
      electroencephalographic (EEG) recording during voluntary and passive finger
      extensions. We recorded somatosensory-evoked potentials following median nerve
      stimulation and performed myoclonic jerk-locked back-averaging of EEG activity.
      RESULTS: Back-averaging revealed a cortical premyoclonic spike in all patients.
      Five of the nine patients had exaggerated SEPs. The amplitude of mu ERD was
      greater in patients. Beta ERD/ERS did not differ from that seen in controls.
      Localizations of mu and beta ERD/ERS did not differ from controls and were
      identified in pre- and post-central sensorimotor cortical areas. CONCLUSIONS: The
      present results suggest a hyperexcitability of the cortico-subcortical loops
      responsible for movement preparation and execution. Post-movement inhibition
      related to cortical processing of afferent input is unaffected in isolated
      cortical myoclonus. SIGNIFICANCE: Intracortical abnormalities can differ in
      patients suffering from cortical myoclonus, according to whether or not the
      individuals have associated epileptic symptoms.

PMID- 22138353
TI  - Developmental thyroid hormone disruption: prevalence, environmental contaminants
      and neurodevelopmental consequences.
AB  - Thyroid hormones (TH) are critical for growth and development and particularly
      brain development. There are numerous environmental agents that lead to marginal
      reductions of circulating TH. Although it is clear that severe developmental
      hypothyroidism is profoundly detrimental to neurodevelopment, there is less
      information regarding the consequences of modest degrees of thyroid. The impact
      of low level TH disruptions induced by environmental contaminants has not been
      defined. This paper is a synopsis from four invited speakers who presented at the
      13th International Neurotoxicology Association meeting held in Xi'an, China
      during the summer of 2011. An overview of the role of TH in brain development and
      a review of human and animal data on the neurological sequelae of disruption of
      the thyroid axis in the pre- and early post-natal periods were presented by Mary
      Gilbert and Joanne Rovet. Iodine deficiency, a common cause of TH insufficiency
      and mental retardation in many countries, including China, was addressed by Zupei
      Chen. In this presentation the current incidence of iodine deficiency and
      neurological outcome in China and the efficacy of recently implemented
      iodinization programs to eliminate this cause of mental retardation were
      reviewed. Joanne Rovet described the impact of TH disruption during pregnancy and
      under conditions of congenital hypothyroidism. Children born with normal thyroid
      function, but who experienced TH insufficiency in the womb, display subtle
      cognitive impairments and abnormalities in brain imaging. Despite early detection
      and treatment, deficiencies also exist in children born with thyroid disorders.
      Different patterns of cognitive effects result from prenatal versus postnatal TH
      insufficiency. Mary Gilbert reported on the effects of environmental contaminants
      with thyroid disrupting action on brain development in animals. Results of
      neurophysiological, behavioral, structural and molecular alterations that
      accompany modest perturbations of the thyroid axis were reviewed. Noriyuki
      Koibuchi described molecular targets of TH-mediated signalling accompanying
      exposure to persistent organic pollutants. Both polychlorinated biphenyls (PCBs)
      and polybrominated diphenyl ethers (PBDEs) are prevalent environmental
      contaminants that disrupt TH signalling at the receptor level. This action by
      these chemical classes could contribute to the negative impact of these chemicals
      on brain function. In summary, epidemiological, preclinical and animal research
      has clearly identified the critical role of TH in brain development. Additional
      work is required to understand the impact of low level perturbations of the
      thyroid axis to evaluate the risk associated with environmental contaminants with
      thyroid action.

PMID- 22138354
TI  - An action research approach for the professional development of Vietnamese nurse
      educators.
AB  - Nurse education in Viet Nam is undergoing substantial reform. In order to
      facilitate the change, in 2007 the Viet Nam Nurses Association formed a
      collaborative partnership with the School of Nursing and Midwifery at an
      Australia university. This collaboration gave rise to the Viet Nam Nursing
      Capacity Building Project under the leadership of Professor Genevieve Gray,
      funded by the Atlantic Philanthropies. The new four year competency based nursing
      curriculum frame is expected to be implemented in September 2011 following
      approval by the Viet Nam Ministry of Education. The focus of this paper is the
      Teaching Fellowship Program, an initiative of the Viet Nam Nursing Capacity
      Building Project, developed to help meet the challenges associated with leading
      and dealing with the curriculum change. The paper explores the development of the
      program and justifies an action research approach, illuminates key issues, and
      briefly refers to changes to the next fellowship program.

PMID- 22138355
TI  - Usefulness of first-line combination therapy with epoprostenol and bosentan in
      pulmonary arterial hypertension: an observational study.
AB  - BACKGROUND: Recent guidelines have proposed first-line combination therapy as a
      potential strategy for the treatment of functional class IV pulmonary arterial
      hypertension (PAH). METHODS: We analyzed efficacy and safety of upfront
      epoprostenol and bosentan combination therapy in consecutive patients with
      idiopathic, heritable, or anorexigen-associated PAH and compared outcomes with
      matched controls treated by epoprostenol monotherapy. RESULTS: Data for 16
      functional class III patients and 7 functional class IV patients were analyzed.
      Baseline 6-minute walk distance (6MWD) was 287 +/- 133 meters, mean pulmonary
      artery pressure was 65 +/- 12 mm Hg, cardiac index was 1.8 +/- 0.3 L/min/m(2),
      and pulmonary vascular resistance (PVR) was 1493 +/- 398 dynes/sec/cm(5). After 4
      months, 6MWD and PVR significantly improved to 421 +/- 100 meters and 784 +/- 364
      dynes/sec/cm(5), respectively. These improvements were maintained long-term (30
      +/- 19 months). At 1, 2, 3, and 4 years, overall survival estimates were 100%,
      94%, 94%, and 74%, and transplant-free survival estimates were 96%, 85%, 77%, and
      60%, respectively. Compared with matched controls started on epoprostenol
      monotherapy, there was a trend to an improvement in overall survival (p = 0.07).
      CONCLUSIONS: Initial combination therapy with epoprostenol and bosentan in
      patients with severe PAH is associated with improvements in important outcomes
      such as functional class, exercise capacity, and hemodynamics. This combination
      strategy might also favorably affect overall and transplant-free survival.

PMID- 22138356
TI  - Synapsin peptide fused to E. coli heat-labile toxin B subunit induces regulatory
      T cells and modulates cytokine balance in experimental autoimmune
      encephalomyelitis.
AB  - We previously found that the preventive oral administration of a hybrid
      consisting of the C domain of synapsin and the B subunit of E. coli heat-labile
      enterotoxin (LTBSC) efficiently suppresses experimental autoimmune
      encephalomyelitis (EAE) development in rats. We investigated the effect of LTBSC
      on cytokine expression and on regulatory T (Treg) cells in rats with myelin
      induced EAE. LTBSC treatment increased the frequency of CD4(+)FoxP3(+) Treg cells
      in lymph nodes prior to challenge and in the EAE acute stage. LTBSC also up
      regulated the expression of anti-inflammatory Th2/Th3 cytokines and diminished
      myelin basic protein-specific Th1 and Th17 cell responses in lymph nodes.
      CD4(+)CD25(+) Treg cells from LTBSC treated rats showed stronger suppressive
      properties than Treg cells from controls in vitro. Our observations indicate that
      LTBSC is a useful agent for modulating the autoimmune responses in EAE.

PMID- 22138357
TI  - Acute exacerbation of IPF following diagnostic bronchoalveolar lavage procedures.
AB  - BACKGROUNDS: Bronchoalveolar lavage (BAL) is generally regarded as a safe
      diagnostic procedure. However, acute exacerbation after BAL is increasingly
      recognized as a specific complication for patients with idiopathic pulmonary
      fibrosis (IPF). So far little is known about the correlation between BAL and
      acute exacerbation of IPF (AE-IPF). METHODS: A cohort of 112 IPF patients at a
      single institution was analyzed retrospectively. We defined BAL-related AE-IPF as
      development of AE-IPF within 30 days after the procedure. The incidence rate of
      AE-IPF per person-month during the post-BAL period was compared with that after
      the post-BAL period. The relative risk was estimated as the former rate divided
      by the latter. We also reviewed the previous literature. RESULTS: Four AE-IPF
      cases occurred during the 201 person-month post-BAL period. The risk of AE-IPF
      was significantly elevated within 30 days after BAL (rate ratio = 4.12; 95% CI =
      1.03-12.2). None of the 111 initial BAL procedures were followed by AE-IPF within
      a month. In a post hoc analysis, the relative risk of developing AE after second
      or later BAL procedures was estimated to be considerably higher (rate ratio =
      9.10; 95% CI = 2.27-26.98). Twelve cases of BAL-induced AE-IPF were found in our
      study and in the literature review. Among them, nine showed moderate to severe
      functional impairment, and eight had either findings of leukocytosis, positive C
      reactive protein, or neutrophilia in BAL. CONCLUSIONS: These results suggest that
      IPF patients should be carefully monitored after BAL, especially those with
      functional impairment or active inflammation.

PMID- 22138358
TI  - Direct and indirect contribution of human embryonic stem cell-derived hepatocyte
      like cells to liver repair in mice.
AB  - BACKGROUND & AIMS: Many studies of embryonic stem cells have investigated direct
      cell replacement of damaged tissues, but little is known about how donor cell
      derived signals affect host tissue regeneration. We investigated the direct and
      indirect roles of human embryonic stem cell-derived cells in liver repair in
      mice. METHODS: To promote the initial differentiation of human embryonic stem
      cells into mesendoderm, we activated the beta-catenin signaling pathway with
      lithium; cells were then further differentiated into hepatocyte-like cells. The
      differentiated cells were purified by indocyanine green staining and laser
      microdissection and characterized by immunostaining, polymerase chain reaction,
      biochemical function, electron microscopy, and transplantation analyses. To
      investigate indirect effects of these cells, secreted proteins (secretomes) were
      analyzed by a label-free quantitative mass spectrometry. Carbon tetrachloride was
      used to induce acute liver injury in mice; cells or secreted proteins were
      administered by intrasplenic or intraperitoneal injection, respectively. RESULTS:
      The differentiated hepatocyte-like cells had multiple features of normal
      hepatocytes, engrafted efficiently into mice, and continued to have hepatic
      features; they promoted proliferation of host hepatocytes and revascularization
      of injured host liver tissues. Proteomic analysis identified proteins secreted
      from these cells that might promote host tissue repair. Injection of the secreted
      proteins into injured livers of mice promoted significant amounts of tissue
      regeneration without cell grafts. CONCLUSIONS: Hepatocyte-like cells derived from
      human embryonic stem cells contribute to recovery of injured liver tissues in
      mice, not only by cell replacement but also by delivering trophic factors that
      support endogenous liver regeneration.

PMID- 22138359
TI  - Total and inorganic arsenic concentrations in different species of economically
      important algae harvested from coastal zones of Chile.
AB  - Chile is one of the major producers of phytocolloids extracted from seaweed.
      Multicellular algae are considered to be primary accumulators of arsenic. We
      analyzed 14 species of algae belonging to the groups Rhodophyceae (10),
      Phaeophyceae (3) and Chlorophyceae (1) from different coastal zones of Chile in
      2003-2004. Dry ashing mineralization (for total As) and acid digestion (for
      inorganic As) together with quantification by flow injection hydride generation
      atomic absorption spectrometry (FI-HG-AAS) were employed. In general, total
      arsenic concentrations varied between 3.0 and 68 mg kg(-1), whereas inorganic
      arsenic concentrations ranged between 0.15 and 1.06 mg kg(-1). The algal species
      Durvillaea antarctica and Porphyra columbina, used for direct human consumption,
      did not have inorganic arsenic levels that represent a health risk to consumers.
      Among species used for phytocolloids production, such as Macrocystis piryfera,
      Gracilaria chilensis and Gigartina skottsbergii, observed levels of inorganic
      arsenic were greater than 1 mg kg(-1), the limit value established by the
      regulations of some countries. Among the 14 species of algae tested, inorganic
      arsenic levels were between 0.8% and 13% of the total arsenic concentrations;
      that is, arsenic present in these algae was found primarily as organic arsenic.

PMID- 22138360
TI  - Antioxidant effects of fermented sea tangle (Laminaria japonica) by Lactobacillus
      brevis BJ20 in individuals with high level of gamma-GT: A randomized, double
      blind, and placebo-controlled clinical study.
AB  - A randomized, double-blind, and placebo-controlled clinical study was performed
      to evaluate the antioxidant effects of fermented sea tangle (FST) on healthy
      volunteers with high levels of gamma-glutamyltransferse (gamma-GT). Forty-eight
      participants were divided into a placebo group and an FST group that received FST
      (1.5 g/day) for 4 weeks. Serum gamma-GT, malondialdehyde (MDA), catalase (CAT),
      superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were
      determined before and after the trial. Administering FST significantly decreased
      serum levels of gamma-GT and MDA. Additionally, SOD and CAT activities were
      significantly augmented compared to those in the placebo group after 4 weeks, but
      no significant alteration was observed in GPx activity compared to that in the
      placebo group. Our findings indicate that FST enhanced the antioxidant defense
      system in a healthy population and may be useful as a functional food ingredient.

PMID- 22138361
TI  - Effect of the oral intake of yogurt containing Bifidobacterium longum BB536 on
      the cell numbers of enterotoxigenic Bacteroides fragilis in microbiota.
AB  - Enterotoxigenic Bacteroides fragilis (ETBF) strains have been suggested to be
      associated with acute and persistent diarrheal disease, inflammatory bowel
      disease and colorectal cancer, although further epidemiological studies are
      needed for clarification. Here, a pilot study was performed to examine the effect
      of the oral administration of yogurt supplemented with a probiotic strain on the
      cell numbers of fecal ETBF in a healthy population. Among 420 healthy adults, 38
      subjects were found to be ETBF carriers, giving a prevalence of approximately 9%.
      Among them, 32 subjects were enrolled in an open, randomized, parallel-group
      study to ingest yogurt supplemented with a probiotic strain, Bifidobacterium
      longum BB536 (BB536Y group), for 8 weeks, with milk provided to the control group
      (milk group). The cell numbers of ETBF and the dominant species of the B.
      fragilis group were measured by a quantitative PCR method. Compared with the
      baseline values, there was a significant decrease in the cell number of ETBF at
      week 8 in the BB536Y group but not in the milk group. Linear mixed models
      analysis for longitudinal data revealed a significant difference in the changes
      of ETBF cell number between the two groups during the intervention phase. These
      results imply the potential of probiotic yogurt for eliminating ETBF in the
      microbiota, but its clinical significance needs to be evaluated in the future.
      This is the first report of a possible effect of probiotic intake on ETBF in the
      microbiota.

PMID- 22138362
TI  - Integrated annotation and analysis of genetic variants from next-generation
      sequencing studies with variant tools.
AB  - MOTIVATION: Storing, annotating and analyzing variants from next-generation
      sequencing projects can be difficult due to the availability of a wide array of
      data formats, tools and annotation sources, as well as the sheer size of the data
      files. Useful tools, including the GATK, ANNOVAR and BEDTools can be integrated
      into custom pipelines for annotating and analyzing sequence variants. However,
      building flexible pipelines that support the tracking of variants alongside their
      samples, while enabling updated annotation and reanalyses, is not a simple task.
      RESULTS: We have developed variant tools, a flexible annotation and analysis
      toolset that greatly simplifies the storage, annotation and filtering of variants
      and the analysis of the underlying samples. variant tools can be used to manage
      and analyze genetic variants obtained from sequence alignments, and the command
      line driven toolset could be used as a foundation for building more sophisticated
      analytical methods. AVAILABILITY AND IMPLEMENTATION: variant tools consists of
      two command-line driven programs vtools and vtools_report. It is freely available
      at http://varianttools.sourceforge.net, distributed under a GPL license. CONTACT:
      bpeng@mdanderson.org.

PMID- 22138363
TI  - Selected papers from the 2011 Summit on Clinical Research Informatics.

PMID- 22138364
TI  - The joint summits on translational science: crossing the translational chasm.

PMID- 22138365
TI  - Parental and romantic attachment shape brain processing of infant cues.
AB  - Periods of bond formation are associated with evolutionary-adaptive
      reorganization of physiological and behavioral responses and increased attention
      to attachment-related cues. We measured event-related potential responses to
      infant stimuli among new parents, new lovers, and romantically unattached singles
      (N=65). For parents, infant stimuli included own and unfamiliar infant. Viewing
      unfamiliar infants, parents and lovers exhibited greater activation at 140-160
      and 300-500 ms post-stimulus compared to singles at occipital-lateral (N170) and
      central-frontal (P3a) sites, indicating greater initial attention to infant cues.
      Parents exhibited lowest amplitudes in the parietal-distributed P300 component,
      implicated in controlled attention, towards the unfamiliar infant but greatest
      response to their own infant in the same waveform. These findings are the first
      to demonstrate that periods of bond formation activate brain reactivity to
      parenting-related cues. Parents' heightened response to own infant accords with
      evolutionary models underscoring the need to direct resources to the survival and
      well being of one's own offspring.

PMID- 22138366
TI  - Effort reward imbalance, and salivary cortisol in the morning.
AB  - BACKGROUND: Effort reward imbalance (ERI) is suggested to increase risk for
      stress and is hypothesized to increase cortisol levels, especially the awakening
      cortisol response, ACR. METHODS: In 2006 and 2008, 480 individuals collected
      saliva samples at awakening and 30 min post-awakening. Mixed effects models with
      subject as a random effect and appropriate covariates were used to evaluate
      associations between the Effort Reward Model, and salivary cortisol at awakening
      (S0), and ACR. RESULTS: ERI was negatively and significantly associated with S0
      for women and positively associated with ACR. S0 and ACR increased significantly
      from 2006 to 2008. CONCLUSION: ERI was significantly associated with cortisol
      levels at awakening (inverse association) for women, and positively associated
      with ACR. The population experienced a significant increase in morning cortisol
      levels and ACR from 2006 to 2008, which may originate in a re-organization of the
      included work places.

PMID- 22138367
TI  - Statistical strategies to quantify respiratory sinus arrhythmia: are commonly
      used metrics equivalent?
AB  - Three frequently used RSA metrics are investigated to document violations of
      assumptions for parametric analyses, moderation by respiration, influences of
      nonstationarity, and sensitivity to vagal blockade. Although all metrics are
      highly correlated, new findings illustrate that the metrics are noticeably
      different on the above dimensions. Only one method conforms to the assumptions
      for parametric analyses, is not moderated by respiration, is not influenced by
      nonstationarity, and reliably generates stronger effect sizes. Moreover, this
      method is also the most sensitive to vagal blockade. Specific features of this
      method may provide insights into improving the statistical characteristics of
      other commonly used RSA metrics. These data provide the evidence to question,
      based on statistical grounds, published reports using particular metrics of RSA.

PMID- 22138368
TI  - Atomistic models of ion and solute transport by the sodium-dependent secondary
      active transporters.
AB  - The recent determination of high-resolution crystal structures of several
      transporters offers unprecedented insights into the structural mechanisms behind
      secondary transport. These proteins utilize the facilitated diffusion of the ions
      down their electrochemical gradients to transport the substrate against its
      concentration gradient. The structural studies revealed striking similarities in
      the structural organization of ion and solute binding sites and a well-conserved
      inverted-repeat topology between proteins from several gene families. In this
      paper we will overview recent atomistic simulations applied to study the
      mechanisms of selective binding of ion and substrate in LeuT, Glt, vSGLT and
      hSERT as well as its consequences for the transporter conformational dynamics.
      This article is part of a Special Issue entitled: Membrane protein structure and
      function.

PMID- 22138369
TI  - Late hepatitis B virus reactivation after lamivudine prophylaxis interruption in
      an anti-HBs-positive and anti-HBc-negative patient treated with rituximab
      containing therapy.
AB  - We describe a case of an anti-HBs-positive patient who experienced hepatitis B
      reactivation 18 months after the discontinuation of rituximab and after 12 months
      of lamivudine prophylaxis. The patient carried a hepatitis B genotype D virus
      harbouring a single immune escape mutation, sT118K. No consensus guidelines
      regarding the optimal length of treatment or the best elective drug have been
      defined for antiviral prophylaxis for HBsAg-negative, anti-HBc- and/or anti-HBs
      positive patients undergoing immunosuppressive treatment. Screening based on HBV
      serological markers and HBV DNA testing is a critical issue to recognise
      hepatitis B reactivation as early as possible. Furthermore, it is of outstanding
      importance to identify alternative markers (e.g. cccDNA, HBV core related
      antigen, etc.), that could be predictive of HBV reactivation.

PMID- 22138370
TI  - Safety profile of Alzheimer's disease populations in Alzheimer's Disease
      Neuroimaging Initiative and other 18-month studies.
AB  - BACKGROUND: Demonstration of a disease-modifying effect of a therapeutic agent on
      Alzheimer's disease (AD) requires a trial lasting for at least 18 months. An
      understanding of expected rates of adverse events (AEs), overall
      discontinuations, and discontinuations due to AEs, serious AEs, and deaths would
      be useful in planning such trials. METHODS: We examined safety information for
      patients taking placebo from five published 18-month AD trials and for patients
      from the Alzheimer's Disease Neuroimaging Initiative study. RESULTS: AEs reported
      consistently across multiple studies were dyspnea (occurring in 5.3%-5.8% of
      patients), headache (4.0%-5.5%), constipation (4.3%-4.7%), nausea (2.0%-5.8%),
      joint swelling (3.6%-3.7%), vomiting (3.6%-3.7%), and anxiety (3.2%-3.6%). Larger
      multinational studies, as compared with smaller studies with fewer sites and
      geographies, demonstrated greater overall discontinuations (24.6%-33.0% vs 8.2%
      21.0%) and greater discontinuations due to AEs (9.5%-11.6% vs 2.7%-3.2%). Rates
      of death (1.8%-2.4%) and SAEs (19.9%-21.2%) were consistent across 18 month
      published studies and in ADNI; fall was the most common SAE (2.6%-4.0%) where
      SAEs were reported. CONCLUSIONS: In general, comparable types of AEs, frequency
      of deaths, and serious AEs were seen for patients taking placebo in five
      randomized, controlled 18-month AD trials and in Alzheimer's Disease Neuroimaging
      Initiative, whereas rates of discontinuations were more variable. Evaluation
      across studies was complicated by inconsistent methods of reporting safety
      information. Evaluation of large databases of placebo patients from therapeutic
      AD trials is needed to further enhance the understanding of expected safety
      outcomes in clinical trials of AD patients.

PMID- 22138371
TI  - Context-dependent brightness priming occurs without visual awareness.
AB  - Our visual systems account for stimulus context in brightness perception, but
      whether such adjustments occur for stimuli that we are unaware of has not been
      established. We therefore assessed whether stimulus context influences brightness
      processing by measuring unconscious priming with metacontrast masking. When a
      middle-gray disk was presented on a darker (or brighter) background, such that it
      could be consciously perceived as brighter (or darker) via simultaneous
      brightness contrast (SBC), reaction times were significantly faster to a bright
      (or dark) annulus than to a dark (or bright) annulus. We further show that
      context-dependent brightness priming does not correlate with visibility using an
      objective measure of awareness (Experiment 1) and that context-dependent, but not
      context-independent brightness priming, occurs equally strongly for stimuli below
      or above the subjective threshold for awareness (Experiment 2). These results
      suggest that SBC occurs at early levels of visual input and is not influenced by
      conscious perception.

PMID- 22138372
TI  - Prostaglandin E2 promotes wound-induced migration of intestinal subepithelial
      myofibroblasts via EP2, EP3, and EP4 prostanoid receptor activation.
AB  - Intestinal subepithelial myofibroblasts (ISMFs) are mesenchymal cells that reside
      in the subepithelial region throughout the intestine. When the intestine is
      damaged, the migratory and mitotic responses of ISMFs are crucial for wound
      closure. However, their mechanism of action remains unknown. We have investigated
      the role of cyclooxygenase (COX) and its metabolite prostaglandin E(2) (PGE(2))
      in the wound repair process of bovine ISMFs. The action of a mechanical scratch
      in a layer of ISMFs in cell culture elevated the levels of both COX-2 mRNA
      expression and PGE(2) secretion 1 and 6 h after the event. After 24 h ISMFs had
      migrated to and reduced the wounded area around the site of the scratch.
      Treatment with the COX-1/2 inhibitor indomethacin, the COX-2 inhibitor 3-(4
      methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole (CAY10404), or E
      prostanoid receptor 2 to 4 (EP2-EP4) antagonists significantly inhibited wound
      repair. Conversely, inhibition of wound closure by indomethicin was reversed by
      treatment with PGE(2) or agonists of the receptors EP2, EP3, or EP4 but not of
      EP1. Although EP2 to EP4 stimulation did not influence ISMF proliferation, it did
      stimulate ISMF migration in the transwell cell migration assay. It is noteworthy
      that cell migration stimulated by EP2 and EP4 was inhibited by the tyrosine
      kinase receptor inhibitor genistein and also by (Z)-3-[2,4-dimethyl-5-(2-oxo-1,2
      dihydro-indol-3-ylidenemethyl)-1H-pyrrol-3-yl]-propionic acid (SU6668). However,
      cell migration stimulated by EP3 was unaffected. Reverse transcription-polymerase
      chain reaction showed EP2 or EP4 stimulation elevated the level of mRNA
      expression for fibroblast growth factor-2, which stimulates ISMF migration.
      Collectively, COX-2-dependent PGE(2) secretion promotes wound healing by ISMFs.
      PGE(2)-EP3 signaling may directly stimulate ISMF migration. PGE(2)-EP2/4
      signaling indirectly stimulates ISMF migration by elevating the level of growth
      factor secretion.

PMID- 22138373
TI  - A phase II study single agent of aflibercept (VEGF Trap) in patients with
      recurrent or metastatic gynecologic carcinosarcomas and uterine leiomyosarcoma. A
      trial of the Princess Margaret Hospital, Chicago and California Cancer Phase II
      Consortia.
AB  - OBJECTIVE: The aim of this multi-institutional non randomized phase II trial was
      to determine the efficacy and safety of single agent aflibercept (VEGF Trap), a
      recombinant fusion protein that blocks multiple vascular endothelial growth
      factor isoforms, in women with gynecologic soft tissue sarcoma. METHODS: Patients
      were enrolled in two cohorts each with Simon two stage designs: uterine
      leiomyosarcoma and carcinosarcoma of endometrial, ovarian or fallopian tube
      origin. Eligibility criteria included <=2 prior lines of chemotherapy for
      metastatic disease and ECOG performance status of <=2. Aflibercept 4mg/kg was
      administered intravenously on day 1 of a 14 day cycle. Primary endpoints were
      objective response and disease stabilization (Progression Free Survival (PFS) at
      6 months). RESULTS: 41 patients with uterine leiomyosarcoma and 22 patients with
      carcinosarcoma (19 uterine, 3 ovarian) were enrolled on study. In the
      leiomyosarcoma cohort, eleven (27%) patients had stable disease (SD), 4 with SD
      lasting at least 24 weeks. The 6 month PFS was 17%, with median time to
      progression (TTP) of 1.8 (95% CI:1.6-2.1) months. In the carcinosarcoma cohort,
      two (9%) patients had SD, one lasting >24 weeks, median TTP was 1.6 months
      (95%CI: 1.1-1.7) No partial responses were observed in patients from either
      cohort. Grade 3 or more aflibercept related toxicity was uncommon and included
      hypertension, fatigue, headache and abdominal pain. CONCLUSIONS: Single agent
      aflibercept has modest activity in patients with uterine leiomyosarcoma and
      minimal activity in women with carcinosarcoma.

PMID- 22138374
TI  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is correlated with 8-hydroxy-2'
      deoxyguanosine in humans after exposure to environmental tobacco smoke.
AB  - Cigarette smoking and exposure to environmental tobacco smoke (ETS) are important
      risk factors for many cancers. However, exposure doses have usually not been
      quantitatively assessed in human studies. In humans 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol and its glucuronate conjugate (defined as total NNAL) are the
      major metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a cigarette
      specific carcinogen. Although animal studies have shown that exposure to
      cigarette smoke increases tissue oxidative DNA damage, the relationship between
      cigarette smoke and 8-hydroxydeoxyguanosine (8-OHdG) is not consistent in human
      studies. In the present study, we have developed a simple, sensitive, and robust
      LC-MS/MS method for quantifying total NNAL and 8-OHdG concentrations in human
      plasma. We quantified total NNAL and 8-OHdG in plasma as well as 8-OHdG in urine
      of 121 healthy male subjects. Total NNAL levels were significantly higher in ever
      smokers than in never-smokers. Furthermore, total NNAL levels in plasma were
      increased with numbers of cigarettes smoked per day in ever-smokers. It suggests
      that total NNAL in plasma is a good biomarker for cigarette smoke exposure. After
      stratifying by smoking status and adjusting for age, ETS exposure and occupation
      category, total NNAL was associated with plasma and urinary 8-OHdG in never
      smokers, but not in ever-smokers. Since total NNAL levels in nonsmokers
      represented the ETS exposure, it appears that 8-OHdG levels are dose-dependently
      correlated with their ETS exposure dose. Furthermore, this correlation supports
      the hypothesis that oxidative DNA damage is one of major adverse effects induced
      by ETS exposure in humans.

PMID- 22138375
TI  - Low level laser therapy (830nm) improves bone repair in osteoporotic rats:
      similar outcomes at two different dosages.
AB  - BACKGROUND AND OBJECTIVE: The goal of this study was to investigate the effects
      of low level laser therapy (LLLT) in osteoporotic rats by means of subjective
      histopathological analysis, deposition of collagen at the site of fracture,
      biomechanical properties and immunohistochemistry for COX-2, Cbfa-1 and VEGF.
      MATERIAL AND METHODS: A total of 30 female Wistar rats (12weeks-old, +/-250g)
      were submitted to ovariectomy (OVX). Eight weeks after the OVX, a tibial bone
      defect was created in all animals and they were randomly divided into 3 groups
      (n=10): control bone defect group (CG): bone defects without any treatment; laser
      60J/cm(2) group (L60): animals irradiated with LLLT, at 60J/cm(2) and laser
      120J/cm(2) group (L120): animals irradiated with LLLT, at 120J/cm(2). RESULTS: In
      the laser treated groups, at both fluences, a higher amount of newly formed bone
      was evidenced as well as granulation tissue compared to control. Picrosirius
      analysis demonstrated that irradiated animals presented a higher deposition of
      collagen fibers and a better organization of these fibers when compared to other
      groups, mainly at 120J/cm(2). COX-2, Cbfa-1 or VEGF immunoreactivity was detected
      in a similar manner either 60J/cm(2) or 120J/cm(2) fluences. However, no
      differences were shown in the biomechanical analysis. CONCLUSION: Taken together,
      our results support the notion that LLLT improves bone repair in the tibia of
      osteoporotic rats as a result of stimulation of the newly formed bone,
      fibrovascularization and angiogenesis.

PMID- 22138376
TI  - Repair of persistent strand breaks in the mitochondrial genome.
AB  - Oxidative DNA damage has been attributed to increased cancer incidence and
      premature aging phenotypes. Reactive oxygen species (ROS) are unavoidable
      byproducts of oxidative phosphorylation and are the major contributors of
      endogenous oxidative damage. To prevent the negative effects of ROS, cells have
      developed DNA repair mechanisms designed to specifically combat endogenous DNA
      modifications. The base excision repair (BER) pathway is primarily responsible
      for the repair of small non-helix distorting lesions and DNA single strand
      breaks. This repair pathway is found in all organisms, and in mammalian cells,
      consists of three related sub-pathways: short patch (SP-BER), long patch (LP-BER)
      and single strand break repair (SSBR). While much is known about nuclear BER,
      comparatively little is known about this pathway in the mitochondria,
      particularly the LP-BER and SSBR sub-pathways. There are a number of proteins
      that have recently been found to be involved in mitochondrial BER, including
      Cockayne syndrome proteins A and B (CSA and CSB), aprataxin (APTX), tryosyl-DNA
      phosphodiesterase 1 (TDP1), flap endonuclease 1 (FEN-1) and exonuclease G (EXOG).
      These significant advances in mitochondrial DNA repair may open new avenues in
      the management and treatment of a number of neurological disorders associated
      with mitochondrial dysfunction, and will be reviewed in further detail herein.

PMID- 22138377
TI  - Pediatric all-terrain vehicle related temporal bone fractures.
AB  - OBJECTIVES: To determine the prevalence of helmet use in children involved in all
      terrain vehicles (ATV) accidents. STUDY DESIGN: Retrospective chart review.
      SETTING: Tertiary Academic Medical Center. SUBJECTS AND METHODS: Retrospective
      review was performed using the trauma registry of an academic tertiary medical
      center identifying ATV injured patients under 13 years of age between 2003-2008.
      Data regarding age, gender, ethnicity, driver/passenger status, helmet status,
      length of hospital stay, Glascow Coma Scale, Injury Severity Score, Abbreviated
      Injury Score, and presence of temporal bone fracture were analyzed. RESULTS:
      Seventy-four ATV injured pediatric subjects were identified. Average age was 8.6
      years, 62% male, 38 were drivers, 32 were passengers. Helmet use data were
      available on 47 (64%) subjects, of these 9 (19%) wore helmets, and 38 (81%) were
      not wearing helmets. There was no observed statistical difference between
      helmeted and unhelmeted riders when comparing age, gender, ethnicity,
      driver/passenger status, length of hospital stay, Glascow Coma Scale (GCS),
      Injury Severity Score, Abbreviated Injury Score, or presence of temporal bone
      fracture. CONCLUSIONS: This review found that documented helmet use in pediatric
      ATV injuries to be profoundly low (19%). Within our cohort no protective benefit
      from helmet use was identified, suggesting the inherent and potentially
      unalterable dangers of pediatric ATV recreation.

PMID- 22138378
TI  - Prevalence of inhaled antigen sensitization and nasal eosinophils in Japanese
      children under two years old.
AB  - OBJECTIVE: The increasingly younger age of onset of allergic rhinitis (AR) has
      recently become a problem. This study examined the prevalence of inhaled antigen
      sensitization and nasal eosinophils in children younger than two years old, with
      measurement of the serum concentrations of aeroallergen-specific IgE antibodies
      to house dust mites, cat fur, and Japanese cedar pollen, measurement of nasal
      eosinophil counts, and a questionnaire administered to the children's parents.
      METHODS: The subjects were a group of healthy children undergoing 18-month infant
      health checks provided by the local government, and sick children younger than
      two years old at the pediatric hospital. RESULTS: Among 408 healthy infants, 44
      (10.7%) had antigen-specific IgE antibodies, 29 (7.1%) had nasal eosinophils, and
      eight (2.0%) had both specific IgE antibodies and nasal eosinophils. Nasal
      assessment revealed that 125 children had rhinorrhea. Of the infants who showed
      both sensitization to antigens and nasal eosinophils, six (1.5%) had confirmed
      rhinorrhea. Among 186 sick children younger than two years old at the pediatric
      hospital, aeroallergen-specific IgE antibodies were detected in five (2.6%). The
      presence of nasal eosinophils was confirmed in six children (3.2%), which
      percentage was smaller than that of the healthy group. No infant had either
      sensitization to antigens or nasal eosinophils. CONCLUSION: The findings
      described above indicate that the minimum prevalence of AR might be 1.5% in 18
      month-old children and that around 10% of affected children have aeroallergen
      specific IgE antibodies in Japan. The incidence of AR in young children might
      increase further.

PMID- 22138380
TI  - Patents discipline is key to securing big pharma investment.

PMID- 22138379
TI  - Chronic pain, addiction severity, and misuse of opioids in Cumberland County,
      Maine.
AB  - BACKGROUND: Few studies have examined the relationship between chronic pain and
      opioid abuse in non-clinical populations. We sought to investigate this in a
      street-recruited sample of active opioid abusers in Cumberland County, Maine,
      USA, a locale that had experienced substantial increases in opioid abuse.
      METHODS: A community-based sample was recruited using respondent-driven sampling.
      Participants were screened to identify those who had consumed illicit opioids in
      the prior month and administered a structured survey that included the Addiction
      Severity Index (ASI) and Brief Pain Inventory(r) (BPI). RESULTS: More than 40% of
      the 237 individuals reported recurring pain that interfered with daily living.
      For more than three-quarters of those reporting chronic pain, opioid misuse
      preceded the onset of chronic pain. The order of onset was not associated with
      differences in sociodemographic, current levels of drug misuse, or ASI and BPI
      scores. BPI scores were associated with medical and psychological ASI domains.
      Compared to those not reporting chronic pain, those doing so were more likely to
      have a regular physician but were more likely to report difficulty gaining
      admission to substance abuse treatment programs. CONCLUSION: Chronic pain was a
      common co-occurring condition among individuals misusing opioids. Better efforts
      are needed to integrate pain management and substance abuse treatment for this
      population.

PMID- 22138381
TI  - The embryonic development of the centipede Strigamia maritima.
AB  - The geophilomorph centipede Strigamia maritima is an emerging model for studies
      of development and evolution among the myriapods. A draft genome sequence has
      recently been completed, making it also an important reference for comparative
      genomics, and for studies of myriapod physiology more generally. Here we present
      the first detailed description of myriapod development using modern techniques.
      We describe a timeline for embryonic development, with a detailed staging system
      based on photographs of live eggs and fixed embryos. We show that the early,
      cleavage and nuclear migration, stages of development are remarkably prolonged,
      accounting for nearly half of the total developmental period (approx 22 of 48
      days at 13  degrees C). Towards the end of this period, cleavage cells migrate to
      the egg periphery to generate a uniform blastoderm. Asymmetry quickly becomes
      apparent as cells in the anterior half of the egg condense ventrally to form the
      presumptive head. Five anterior segments, the mandibular to the first leg-bearing
      segment (1st LBS) become clearly visible through the chorion almost
      simultaneously. Then, after a short pause, the next 35 leg-bearing segments
      appear at a uniform rate of 1 segment every 3.2 h (at 13  degrees C). Segment
      addition then slows to a halt with 40-45 LBS, shortly before the dramatic
      movements of germ band flexure, when the left and right halves of the embryo
      separate and the embryo folds deeply into the yolk. After flexure, segment
      morphogenesis and organogenesis proceed for a further 10 days, before the egg
      hatches. The last few leg-bearing segments are added during this period, much
      more slowly, at a rate of 1-2 segments/day. The last leg-bearing segment is fully
      defined only after apolysis of the embryonic cuticle, so that at hatching the
      embryo displays the final adult number of leg-bearing segments (typically 47-49
      in our population).

PMID- 22138382
TI  - Interaction of modified tail-anchored proteins with liposomes: effect of
      extensions of hydrophilic segment at the COOH-terminus of holo-cytochromes b5.
AB  - A group of membrane proteins having a single COOH-terminal hydrophobic domain
      capable of post-translational insertion into lipid bilayer is known as tail
      anchored (TA) proteins. To clarify the insertion mechanism of the TA-domain of
      human cytochrome b(5) (Hcytb5) into ER membranes, we produced and purified
      various membrane-bound forms of Hcytb5 with their heme b-bound, in which various
      truncated forms of NH(2)-terminal bovine opsin sequence were appended at the COOH
      terminus of the native form. We analyzed the integration of the TA-domains of
      these forms onto protein-free liposomes. The integration occurred efficiently
      even in the presence of a small amount of sodium cholate and, once incorporated,
      such proteoliposomes were very stable. The mode of the integration was further
      analyzed by treatment of the proteoliposomes with trypsin either on the
      extravesicular side or on the luminal side. LC-MS analyses of the trypsin digests
      obtained from the proteoliposomes indicated that most of the C-terminal
      hydrophilic segment of the native Hcytb5 were exposed towards the lumen of the
      vesicles and, further, a significant part of the population of the extended C
      terminal hydrophilic segments of the modified Hcytb5 were exposed in the lumen as
      well, suggesting efficient translocation ability of the TA-domain without any
      assistance from other protein factors. Present results opened a route for the use
      of the C-terminal TA-domain as a convenient tool for the transport of proteins as
      well as short peptides into artificial liposomes.

PMID- 22138383
TI  - Evaluation of the implant type tissue-engineered cartilage by scanning acoustic
      microscopy.
AB  - The tissue-engineered cartilages after implantation were nonuniform tissues which
      were mingling with biodegradable polymers, regeneration cartilage and others. It
      is a hard task to evaluate the biodegradation of polymers or the maturation of
      regenerated tissues in the transplants by the conventional examination.
      Otherwise, scanning acoustic microscopy (SAM) system specially developed to
      measure the tissue acoustic properties at a microscopic level. In this study, we
      examined acoustic properties of the tissue-engineered cartilage using SAM, and
      discuss the usefulness of this devise in the field of tissue engineering. We
      administered chondrocytes/atelocollagen mixture into the scaffolds of various
      polymers, and transplanted the constructs in the subcutaneous areas of nude mice
      for 2 months. We harvested them and examined the sound speed and the attenuation
      in the section of each construct by the SAM. As the results, images mapping the
      sound speed exhibited homogenous patterns mainly colored in blue, in all the
      tissue-engineered cartilage constructs. Contrarily, the images of the attenuation
      by SAM showed the variation of color ranged between blue and red. The low
      attenuation area colored in red, which meant hard materials, were corresponding
      to the polymer remnant in the toluidine blue images. The localizations of blue
      were almost similar with the metachromatic areas in the histology. In conclusion,
      the SAM is regarded as a useful tool to provide the information on acoustic
      properties and their localizations in the transplants that consist of
      heterogeneous tissues with various components.

PMID- 22138384
TI  - Visual expression analysis of the responses of the alternative oxidase gene
      (aox1) to heat shock, oxidative, and osmotic stresses in conidia of citric acid
      producing Aspergillus niger.
AB  - The citric acid-producing filamentous fungus Aspergillus niger WU-2223L shows
      cyanide-insensitive respiration catalyzed by alternative oxidase in addition to
      the cytochrome pathway. Sequence analysis of the 5' flanking region of the
      alternative oxidase gene (aox1) revealed a potential heat shock element (HSE) and
      a stress response element (STRE). We have previously confirmed aox1 expression in
      conidia. In this study, to confirm whether the upstream region of aox1 responds
      to various stresses, we used a visual expression analysis system for single-cell
      conidia of the A. niger strain AOXEGFP-1. This strain harbored a fusion gene
      comprising aox1 and egfp, which encodes the enhanced green fluorescent protein
      (EGFP). The fluorescence intensity of EGFP increased in conidia of A. niger
      AOXEGFP-1 that were subjected to heat shock at 35-45  degrees C, oxidative stress
      by exposure to 5mM paraquat or 1 mM t-butylhydroperoxide, or osmotic stresses by
      exposure to 0.5 M KCl or 1.0 M mannitol. These results indicate that the putative
      HSE and STRE in the upstream region of aox1 directly or indirectly respond to
      heat shock, oxidative, and osmotic stresses.

PMID- 22138385
TI  - Improvement of neuronal cell adhesiveness on parylene with oxygen plasma
      treatment.
AB  - We improved adhesiveness of a neuron-like cell, PC12, on a Parylene-C surface by
      O(2) plasma treatment which changes the surface from hydrophobic to hydrophilic.
      Neural cell adhesiveness on the plasma-treated Parylene-C was more than twenty
      times better compared to non-treated Parylene-C and it was close to that on a
      conventional polystyrene tissue-culture dish.

PMID- 22138386
TI  - Importance of metabolic coupling for the dynamics of gene expression following a
      diauxic shift in Escherichia coli.
AB  - Gene regulatory networks consist of direct interactions, but also include
      indirect interactions mediated by metabolism. We investigate to which extent
      these indirect interactions arising from metabolic coupling influence the
      dynamics of the system. To this end, we build a qualitative model of the gene
      regulatory network controlling carbon assimilation in Escherichia coli, and use
      this model to study the changes in gene expression following a diauxic shift from
      glucose to acetate. In particular, we compare the relative variation in the
      steady-state concentrations of enzymes and transcription regulators during growth
      on glucose and acetate, as well as the dynamic response of gene expression to the
      exhaustion of glucose and the subsequent assimilation of acetate. We find
      significant differences between the dynamics of the system in the absence and
      presence of metabolic coupling. This shows that interactions arising from
      metabolic coupling cannot be ignored when studying the dynamics of gene
      regulatory networks.

PMID- 22138387
TI  - Mean pulmonary arterial pressure after percutaneous mitral valvuloplasty predicts
      long-term adverse outcomes.
AB  - INTRODUCTION AND AIM: Percutaneous mitral valvuloplasty (PMV) is an effective
      treatment option for mitral stenosis (MS), but its success is assessed on the
      basis of clinical and echocardiographic outcomes in studies with relatively short
      follow-up. We aimed to characterize a cohort of patients undergoing PMV with long
      term follow-up and to determine independent predictors of post-PMV mitral re
      intervention and event-free survival. METHODS: We studied 91 consecutive patients
      with MS who underwent PMV with a median clinical follow-up duration of 99 months.
      Two endpoints were considered: post-PMV mitral re-intervention (PMV or mitral
      surgery) and a composite clinical events endpoint including cardiovascular death,
      mitral valve re-intervention and hospital admission due to decompensated heart
      failure. We compared patients who required post-PMV mitral re-intervention with
      those who did not during follow-up. RESULTS: The study population included 83.5%
      females and mean age was 48.9+/-13.9 years. The 1-, 3-, 5-, 7- and 9-year rates
      of clinical event-free survival were 93.0+/-2.8%, 86.0+/-3.9%, 81.0+/-4.4%,
      70.6+/-5.6%, and 68.4+/-5.8%, respectively. The 1-, 3-, 5-, 7- and 9-year rates
      of mitral re-intervention-free survival were 98.8+/-1.2%, 97.5+/-1.7%, 92.1+/
      3.1%, 85.5+/-4.5%, and 85.5+/-4.5%, respectively. The median time to mitral re
      intervention was 6.2 years. Patients who required mitral re-intervention during
      follow-up were younger (43.3 vs. 51.2 years, p=0.04) and had higher pre- and post
      PMV mitral gradient (14.9 vs. 11.5 mmHg, p=0.02 and 6.4 vs. 2.1 mmHg, p<0.001)
      and higher post-PMV mean pulmonary artery pressure (mPAP) (30.0 vs. 23.2 mmHg,
      p=0.01). In a Cox proportional hazards model, mPAP >=25 mmHg was the sole
      predictor of both mitral re-intervention (HR 5.639 [1.246-25.528], p=0.025) and
      clinical events (HR 3.622 [1.070-12.260], p=0.039). CONCLUSION: In our
      population, immediate post-PMV mPAP was the sole predictor of post-PMV mitral
      intervention. These findings may help identify patients in need of closer post
      PMV follow-up.

PMID- 22138388
TI  - Structure and function of focal adhesions.
AB  - Integrin-dependent cell adhesions come in different shapes and serve in different
      cell types for tasks ranging from cell-adhesion, migration, and the remodeling of
      the extracellular matrix to the formation and stabilization of immunological and
      chemical synapses. A major challenge consists in the identification of adhesion
      specific as well as common regulatory mechanisms, motivating the need for a
      deeper analysis of protein-protein interactions in the context of intact focal
      adhesions. Specifically, it is critical to understand how small differences in
      binding of integrins to extracellular ligands and/or cytoplasmic adapter proteins
      affect the assembly and function of an entire focal adhesion. By using the talin
      integrin pair as a starting point, I would like to discuss how specific protein
      protein and protein-lipid interactions can control the behavior and function of
      focal adhesions. By responding to chemical and mechanical cues several
      allosterically regulated proteins create a dynamic multifunctional protein
      network that provides both adhesion to the extracellular matrix as well as
      intracellular signaling in response to mechanical changes in the cellular
      environment.

PMID- 22138389
TI  - Are antidepressants good for the soul but bad for the matter? Using noninvasive
      brain stimulation to detangle depression/antidepressants effects on heart rate
      variability and cardiovascular risk.

PMID- 22138391
TI  - Variations in the promoter region of the serotonin transporter gene and biased
      attention for emotional information: a meta-analysis.
AB  - BACKGROUND: Selective attention to negative information has been strongly
      implicated in the etiology and maintenance of anxiety and offered as a potential
      intermediate phenotype for anxiety disorders. Attention biases have been studied
      in relation to a polymorphism in the promoter region of the serotonin transporter
      gene (5-HTTLPR) offering equivocal findings. The present meta-analysis tested
      whether the extant published data support the notion that variation in the 5
      HTTLPR genotype modulates selective attention to negative information. METHODS:
      Eleven relevant samples from 10 published articles were identified through a
      systematic literature search (total n = 807). Relevant attention bias and 5
      HTTLPR data were extracted based on specific coding rules, and Cohen's d effect
      size index was used to calculate all outcome measures. Publication bias was
      assessed using various methods. RESULTS: Carriers of the low (SS, SL(G),
      L(G)L(G)) transmission efficacy genotype display attentional vigilance toward
      negatively valenced stimuli, a pattern not found in the intermediate (SL(A),
      L(A)L(G)) and high (L(A)L(A)) efficacy genotypes. This phenomenon emerges as of
      medium effect size. CONCLUSIONS: The meta-analysis supports the notion that
      allele variants of the 5-HTTLPR are associated with selective attention to
      negative stimuli. More studies are needed to fully establish the consistency of
      this effect. Future studies applying systematic attention bias modification may
      shed further light on the role of 5-HTTLPR in the development of anxiety
      disorders and in the prediction of clinical response to attention bias
      modification treatments.

PMID- 22138392
TI  - Emerging role of p62/sequestosome-1 in the pathogenesis of Alzheimer's disease.
AB  - The p62/sequestosome-1 is a multifunctional protein containing several protein
      protein interaction domains. Through these interactions p62 is involved in the
      regulation of cellular signaling and protein trafficking, aggregation and
      degradation. p62 protein can bind through its UBA motif to ubiquitinated proteins
      and control their aggregation and degradation via either autophagy or
      proteasomes. p62 protein has been reported to be seen in association with the
      intracellular inclusions in primary and secondary tauopathies, alpha
      synucleinopathies and other neurodegenerative brain disorders displaying
      inclusions with misfolded proteins. In Alzheimer's disease (AD), p62 protein is
      associated with neurofibrillary tangles composed primarily of hyperphosphorylated
      tau protein and ubiquitin. Increasing evidence indicates that p62 has an
      important role in the degradation of tau protein. The lack of p62 protein
      expression provokes the tau pathology in mice. Recent studies have demonstrated
      that the p62 gene expression and cytoplasmic p62 protein levels are significantly
      reduced in the frontal cortex of AD patients. Decline in the level of p62 protein
      can disturb the signaling pathways of Nrf2, cyclic AMP and NF-kappaB and in that
      way increase oxidative stress and impair neuronal survival. We will review here
      the molecular and functional characteristics of p62 protein and outline its
      potential role in the regulation of Alzheimer's pathogenesis.

PMID- 22138393
TI  - Inactivation of prolyl hydroxylase domain (PHD) protein by epigallocatechin
      (EGCG) stabilizes hypoxia-inducible factor (HIF-1alpha) and induces hepcidin
      (Hamp) in rat kidney.
AB  - HIF-1alpha plays a key role in iron uptake and transport in the liver, whose
      activity is tightly linked to the repression of hepcidin (Hamp). Hamp prevents
      intestinal iron uptake and cellular efflux by negatively modulating ferroportin.
      Hamp is also expressed in the kidneys, where transcriptional control by HIF
      1alpha remains poorly understood. We show that the administration of
      epigallocatechin gallate (EGCG) results in a considerable Hamp expression in rat
      kidneys. We also provide evidence to show that EGCG inhibited prolyl hydroxylase
      (PHD) activity, essential for HIF-1alpha degradation in vivo and in vitro. Rats
      that were dosed with EGCG (60 mg/kg, intraperitoneal) over a 7 day time course
      stabilized HIF-1alpha protein in kidney tissues. Interestingly, Hamp gene
      expression was induced, even after subjecting rats to a 4h hypoxia treatment (8%
      oxygen). Using Hep3B cells, we determined that EGCG conferred its inhibitory
      action by complexing with PHD, altering its catalytic iron center and thus
      preventing HIF-1alpha hydroxylation. These data demonstrate EGCG's therapeutic
      potential in modulating hepcidin expression in diseases associated with altered
      iron metabolism.

PMID- 22138394
TI  - The transiently ordered regions in intrinsically disordered ExsE are correlated
      with structural elements involved in chaperone binding.
AB  - Many Gram-negative bacteria utilize a type III secretion system (T3SS) to deliver
      protein effectors to target host cells. Transcriptional control of T3SS gene
      expression is generally coupled to secretion through the release of a regulatory
      protein. T3SS gene expression in Pseudomonas aeruginosa is regulated by
      extracellular secretion of ExsE. ExsE is a small 81 residue protein that appears
      to lack a stable structural core as indicated by previous studies. In this study,
      we employed various NMR methods to characterize the structure of ExsE alone and
      when bound to its secretion chaperone ExsC. We found that ExsE is largely
      unfolded throughout the polypeptide chain, belonging to a class of proteins that
      are intrinsically disordered. The unfolded, extended conformation of ExsE may
      expedite efficient secretion through the narrow path of the T3SS secretion
      channel to activate gene expression in a timely manner. We also found that the
      structurally flexible ExsE samples through conformations with localized
      structurally ordered regions. Importantly, these transiently ordered elements are
      related to the secondary structures involved in binding ExsC based on a prior
      crystal structure of the ExsC-ExsE complex. These findings support the notion
      that preexisting structured elements facilitate binding of intrinsically
      disordered proteins to their targets.

PMID- 22138396
TI  - WITHDRAWN: Cellular uptake and phototoxicity of bioconjugated fluorescent
      nanodiamonds.
AB  - This article has been withdrawn at the request of the authors. 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- 22138395
TI  - cPLA2alpha-mediated actin rearrangements downstream of the Akt signaling is
      required for Cronobacter sakazakii invasion into brain endothelial cells.
AB  - Cronobacter sakazakii (C. sakazakii) is an opportunistic pathogen that causes
      sepsis and meningitis in neonate. The molecular mechanism involved in the
      pathogenesis of C. sakazakii meningitis remains unclear. In this study, we found
      that C. sakazakii invasion was significantly decreased in human brain
      microvascular endothelial cells (HBMEC) treated with cytosolic phospholipases
      A(2)alpha (cPLA(2)alpha) inhibitor. Increased phosphorylation of cPLA(2)alpha was
      observed in HBMEC infected with C. sakazakii, which was prevented by treatment
      with cPLA(2)alpha inhibitor. cPLA(2)alpha knockdown in HBMEC significantly
      attenuated C. sakazakii invasion into HBMEC. Immunofluorescence demonstrated that
      the rearrangements of actin filaments in HBMEC induced by C. sakazakii were
      effectively blocked by either treatment with cPLA(2)alpha inhibitor or
      transfection with cPLA(2)alpha siRNA. Interestingly, we found that C. sakazakii
      infection promoted the aggregation of phosphorylated cPLA(2)alpha, which was
      associated with depolymerized actin filaments in HBMEC. Furthermore, our data
      revealed that cPLA(2)alpha acts downstream of Akt signaling pathway in HBMEC
      stimulated with C. sakazakii. Taken together, our results illustrated that
      cPLA(2)alpha-mediated actin filament rearrangements downstream of Akt activation
      is required for C. sakazakii invasion into brain endothelial cells.

PMID- 22138397
TI  - Transducible form of p47phox and p67phox compensate for defective NADPH oxidase
      activity in neutrophils of patients with chronic granulomatous disease.
AB  - Protein delivery to primary cells by protein transduction domain (PTD) serves as
      a novel measure for manipulation of the cells for biological study and for the
      treatment of various human conditions. Although the method has been employed to
      modulate cellular function in vitro, only limited reports are available on its
      application in the replacement of deficient signaling molecules into primary
      cells. We examined the potential of recombinant proteins to compensate for
      defective cytosolic components of the NADPH oxidase complex in chronic
      granulomatous disease (CGD) neutrophils in both p47(phox) and p67(phox)
      deficiency. The p47(phox) or p67(phox) protein linked to Hph-1 PTD was
      effectively expressed in soluble form and transduced into human neutrophils
      efficiently without eliciting unwanted signal transduction or apoptosis. The
      delivered protein was stable for more than 24h, expressed in the cytoplasm,
      translocated to the membrane fraction upon activation, and, most importantly able
      to restored reactive oxygen species (ROS) production. Although research on human
      primary neutrophils using the protein delivery system is still limited, our data
      show that the protein transduction approach for neutrophils may be applicable to
      the control of local infections in CGD patients by direct delivery of the protein
      product.

PMID- 22138398
TI  - C-terminal binding protein-mediated transcriptional repression is regulated by X
      linked inhibitor of apoptosis protein.
AB  - Inhibitors of Apoptosis Proteins (IAPs) are known as the key negative regulators
      of apoptosis. To explore new functions of IAPs, we sought to identify proteins
      that interact with Diap1 in insect S2 cells. We found that Diap1 bound to
      Drosophila C-terminal binding protein (dCtBP), which is a transcriptional co
      repressor. CtBP1 also interacted with X-linked inhibitor of apoptosis protein
      (XIAP) in human cells. CtBPs were ubiquitinated by IAPs and targeted for
      proteasome-mediated degradation. Finally, the expression of CtBP1 target genes
      was regulated by XIAP expression. This is the first report to demonstrate that
      XIAP specifically regulates CtBP1, suggesting that XIAP may play a role in
      regulating CtBP1-mediated transcriptional repression by regulating the level of
      CtBP1.

PMID- 22138399
TI  - PrPC interacts with potassium channel tetramerization domain containing 1 (KCTD1)
      protein through the PrP(51-136) region containing octapeptide repeats.
AB  - To identify molecular interaction partners of the cellular prion protein
      (PrP(C)), we applied a yeast two-hybrid screen on a bovine brain cDNA expression
      library and identified the potassium channel tetramerization domain containing 1
      (KCTD1) as a PrP(C) interacting protein. Deletion mapping showed that PrP(C)
      specifically binds KCTD1 through the unstructured PrP(51-136) region. We further
      confirmed the interaction between PrP(C) and KCDT1 protein by co
      immunoprecipitation in vivo and by a biosensor assay in vitro. Interestingly, the
      binding of an insertion mutant PrP(8OR) to KCTD1 is higher than that of wild-type
      PrP(C), suggesting an important role for an unstructured region harboring
      octapeptide repeats in the KCTD1-PrP(C) interaction. Our results identify a novel
      PrP(C)-interacting protein and suggest a new approach to investigating the
      unidentified physiological cellular function of PrP(C).

PMID- 22138400
TI  - Characterization and in vitro interaction study of a [NiFe] hydrogenase large
      subunit from the hyperthermophilic archaeon Thermococcus kodakarensis KOD1.
AB  - The large subunit of the [NiFe] hydrogenases harbors a NiFe(CN)(2)(CO) cluster.
      Maturation proteins HypA, B, C, D, E, and F are required for the NiFe cluster
      biosynthesis. While the maturation machinery has been hitherto studied
      intensively, little is known about interactions between the Hyp proteins and the
      large subunit of the [NiFe] hydrogenase. In this study, we have purified and
      characterized the cytosolic [NiFe] hydrogenase large subunit HyhL from
      Thermococcus kodakarensis (Tk-HyhL). Tk-HyhL exists in equilibrium between
      monomeric and dimeric forms. In vitro interaction analyses showed that Tk-HyhL
      monomer forms a tight complex with Tk-HypA and weakly interacts with Tk-HypC. The
      expected ternary complex formation was not detected. These observations reflect a
      diversity in the mechanism of Ni insertion in [NiFe] hydrogenase maturation
      depending on the organism.

PMID- 22138402
TI  - Frizzled-8 as a putative therapeutic target in human lung cancer.
AB  - Lung cancer is the leading cause of cancer related deaths worldwide. It is
      necessary to better understand the molecular mechanisms involved in lung cancer
      in order to develop more effective therapeutics for the treatment of this
      disease. Recent reports have shown that Wnt signaling pathway is important in a
      number of cancer types including lung cancer. However, the role of Frizzled-8
      (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung
      cancer still remains to be elucidated. Here in this study we showed that Fzd-8
      was over-expressed in human lung cancer tissue samples and cell lines. To
      investigate the functional importance of the Fzd-8 over-expression in lung
      cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing
      the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with
      decreased activity of Wnt pathway in vitro, and also significantly suppressed
      A549 xenograft model in vivo (p<0.05). Furthermore, we found that knocking down
      Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These
      data suggest that Fzd-8 is a putative therapeutic target for human lung cancer
      and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung
      cancer.

PMID- 22138401
TI  - Quercetin protects against pulmonary oxidant stress via heme oxygenase-1
      induction in lung epithelial cells.
AB  - The lung is a primary target for oxygen toxicity because of its constant exposure
      to high oxygen levels and environmental oxidants. Quercetin is one of the most
      commonly found dietary flavonoids, and it provides cytoprotective actions via
      activation of specific transcriptional factors and upregulation of endogenous
      defensive pathways. In the present study, we showed that quercetin increased the
      levels of heme oxygenase (HO)-1 expression and protected against hydrogen
      peroxide (H(2)O(2))-induced cytotoxicity in lung epithelial cell lines. Quercetin
      suppressed H(2)O(2)-induced apoptotic events, including hypodiploid cells,
      activation of caspase 3 enzyme activity and lactate dehydrogenase release. This
      cytoprotective effect was attenuated by the addition of the HO inhibitor, tin
      protoporphyrin IX. In addition, the end products of heme metabolites catalyzed by
      HO-1, carbon monoxide and bilirubin, protect against H(2)O(2)-induced
      cytotoxicity in LA-4 cells. Quercetin may well be one of the promising substances
      to attenuate oxidative epithelial cell injury in lung inflammation.

PMID- 22138404
TI  - Potential health risks from radioactive contamination of saltmarshes in NW
      England.
AB  - The present study focuses on the detection of Sellafield-derived (137)Cs and
      (241)Am in contaminated saltmarshes from North-West England, UK, with a view to
      assessing the radiological impacts from radioactivity stored within the sediment
      record. The surface activities from these radionuclides were found in the range
      between 73 and 851 Bq kg(-1) whereas peak activities ranging from 383 to 12690 Bq
      kg(-1) were found below the surface of the upper marsh at a depth of
      approximately 5-20 cm. Potential radioactive exposure to humans from these highly
      active radionuclides comes mainly from direct exposure and resuspended dust
      inhalation for different saltmarsh users, which may be exacerbated by the
      remobilisation of radionuclides resulting from saltmarsh erosion. The total
      annual minimum, maximum and 'best estimate' doses ranging from 11 to 972 MUSv y(
      1), fall below the ICRP-recommended annual dose limit, but the highest estimated
      total effective dose (972 MUSv y(-1)) for a marsh user falls within 97% of the
      recommended dose limit and the highest 'best estimate' total annual doses of 110
      and 307 MUSv y(-1) for Dee estuary and Biggar marshes, respectively, are almost 3
      and 4 times higher than the estimated doses that are based on existing surface
      activities.

PMID- 22138403
TI  - Cells with dysfunctional telomeres are susceptible to reactive oxygen species
      hydrogen peroxide via generation of multichromosomal fusions and chromosomal
      fragments bearing telomeres.
AB  - During genotoxic stress, reactive oxygen species hydrogen peroxide (H(2)O(2)) is
      a prime mediator of the DNA damage response. Telomeres function both to assist in
      DNA damage repair and to inhibit chromosomal end-to-end fusion. Here, we show
      that telomere dysfunction renders cells susceptible to H(2)O(2), via generation
      of multichromosomal fusion and chromosomal fragments. H(2)O(2) caused formation
      of multichromosomal end-to-end fusions involving more than three chromosomes,
      preferentially when telomeres were erosive. Interestingly, extensive chromosomal
      fragmentation (yielding small-sized fragments) occurred only in cells exhibiting
      such multichromosomal fusions. Telomeres were absent from fusion points, being
      rather present in the small fragments, indicating that H(2)O(2) cleaves
      chromosomal regions adjacent to telomeres. Restoration of telomere function or
      addition of the antioxidant N-acetylcysteine prevented development of chromosomal
      aberrations and rescued the observed hypersensitivity to H(2)O(2). Thus,
      chromosomal regions adjacent to telomeres become sensitive to reactive oxygen
      species hydrogen peroxide when telomeres are dysfunctional, and are cleaved to
      produce multichromosomal fusions and small chromosomal fragments bearing the
      telomeres.

PMID- 22138405
TI  - The ability to interact with cell membranes suggests possible biological roles
      for free light chain.
AB  - During antibody synthesis, immunoglobulin light chains are produced in excess of
      heavy chains and, as a consequence, can be secreted by plasma cells as free light
      chains (FLC). Thus, FLC were considered to be a by-product of immunoglobulin
      synthesis, lacking any biological function or relevance. However, mounting
      evidence suggests that FLC are bioactive molecules. For example, FLC can induce
      antigen specific type I hypersensitivity and inhibit viral replication in
      encephalomyocarditis infected mice. We have recently shown that FLC can associate
      with the outer membrane of certain plasma cells via interaction with saturated
      phosphocholine lipids such as sphingomyelin. As these lipids are highly abundant
      in mammalian cell membranes, we set out to determine whether FLCs can bind to
      membranes from a variety of cell types. We found that FLCs bind to the plasma
      membrane of cells from a wide range of lineages. Interestingly, the highest level
      of binding was to monocytes. As these cells are professional antigen presenting
      cells, we postulate that membrane-associated FLCs may provide a novel mechanism
      of antigen uptake by these cells.

PMID- 22138406
TI  - Soluble B7-H1: differences in production between dendritic cells and T cells.
AB  - Tumor cells aberrantly express several T cell inhibitory molecules including
      members of the B7-H co-regulatory family. Presumably tumor-expressed B7-H1 and B7
      H3 confer resistance to elimination by the immune system. In addition, elevated
      levels of soluble B7-H1 (sB7-H1) has been identified in the sera of cancer
      patients, including renal carcinoma patients and is associated with increased
      cancer related death. Here we report that sB7-H1 is produced and released by
      activated mature dendritic cells (mDC). Immature DC, macrophages, monocytes, or T
      cells are refractory to releasing sB7-H1. Exposure of CD4+ and CD8+ T cells to
      mDC-derived sB7-H1 molecules induced apoptosis. These data suggest that the
      immunobiology of B7-H1 is perhaps more complex than previously thought. sB7-H1
      molecules may represent an unanticipated contributing factor to immune
      homeostasis. That both immune and tumor cells can be sources of sB7-H1 suggests
      that optimization of co-regulatory blockade immunotherapy for solid malignancies
      of necessity will require impact of targeting tumor and immune-derived B7-H1
      molecules.

PMID- 22138407
TI  - The mGluR7 allosteric agonist AMN082 produces antidepressant-like effects by
      modulating glutamatergic signaling.
AB  - Currently prescribed antidepressants affect the reuptake and/or metabolism of
      biogenic amines. Unfortunately for patients, these treatments require several
      weeks to produce significant symptom remission. However, recently it has been
      found that ketamine, a dissociative anesthetic agent that noncompetitively
      antagonizes NMDA (N-Methyl-d-aspartic acid) receptors, has rapid antidepressant
      effects at sub-anesthetic doses in clinically depressed patients. These findings
      indicate that modulation of the glutamatergic system could be an efficient way to
      achieve antidepressant activity. For this reason, other mechanisms influencing
      glutamatergic functioning have gained interest. For example, the metabotropic
      glutamate receptor 7 (mGluR7) allosteric agonist AMN082 (N,N'-dibenzyhydryl
      ethane-1,2-diamine dihydrochloride) has been shown to be effective in the forced
      swim and tail-suspension test, behavioral assays sensitive to antidepressants.
      Here we extend the characterization of AMN082 by demonstrating its effects on
      differential reinforcement of low rates of responding (DRL)-30, another assay
      sensitive to antidepressants. Furthermore, we show the engagement of
      glutamatergic signaling by demonstrating the ability of the selective AMPA (2
      amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid) receptor antagonist NBQX
      (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione) to reverse the
      effects of AMN082 in the tail suspension test. In contrast, NBQX failed to
      reverse the effects of imipramine in the same behavioral test. Finally, we report
      that behaviorally efficacious doses of AMN082 modulate phosphorylation of AMPA
      and NMDA receptor subunits in the hippocampus. These results suggest that the
      antidepressant-like effects of AMN082 are, at least in part, due to modulation of
      AMPA and NMDA receptor activity. Therefore, our findings confirm the hypothesis
      that mGluR7 could represent a novel target for treating depression.

PMID- 22138408
TI  - Functional roles of transferrin in the brain.
AB  - BACKGROUND: Transferrin is synthesized in the brain by choroid plexus and
      oligodendrocytes, but only that in the choroid plexus is secreted. Transferrin is
      a major iron delivery protein to the brain, but the amount transcytosed across
      the brain microvasculature is minimal. Transferrin is the major source of iron
      delivery to neurons. It may deliver iron to immature oligodendrocytes but this
      trophic effect declines over time while iron requirements for maintaining
      myelination continue. Finally, transferrin may play an important role in
      neurodegenerative diseases through its ability to mobilize iron. SCOPE OF REVIEW:
      The role of transferrin in maintaining brain iron homeostasis and the mechanism
      by which it enters the brain and delivers iron will be discussed. Its relevance
      to neurological disorders will also be addressed. MAJOR CONCLUSIONS: Transferrin
      is the major iron delivery protein for neurons and the microvasculature, but has
      a limited role for glial cells. The main source of transferrin in the brain is
      likely from the choroid plexus although the concentration of transferrin at any
      given time in the brain includes that synthesized in oligodendrocytes. Little is
      known about brain iron egress or the role of transferrin in this process. GENERAL
      SIGNIFICANCE: Neuron survival requires iron, which is predominantly delivered by
      transferrin. The concentration of transferrin in the cerebrospinal fluid is
      reflective of brain iron availability and can function as a biomarker in disease.
      Accumulation of iron in the brain contributes to neurodegenerative processes,
      thus an understanding of the role that transferrin plays in regulating brain iron
      homeostasis is essential. This article is part of a Special Issue entitled
      Transferrins: Molecular mechanisms of iron transport and disorders.

PMID- 22138409
TI  - Improving ROSC with high dose of epinephrine. Are we really?

PMID- 22138410
TI  - Should the arrhythmias that occur upon return of spontaneous circulation be
      treated?

PMID- 22138411
TI  - Prospects for translational regenerative medicine.
AB  - Translational medicine is an evolutional concept that encompasses the rapid
      translation of basic research for use in clinical disease diagnosis, prevention
      and treatment. It follows the idea "from bench to bedside and back", and hence
      relies on cooperation between laboratory research and clinical care. In the past
      decade, translational medicine has received unprecedented attention from
      scientists and clinicians and its fundamental principles have penetrated
      throughout biomedicine, offering a sign post that guides modern medical research
      toward a patient-centered focus. Translational regenerative medicine is still in
      its infancy, and significant basic research investment has not yet achieved
      satisfactory clinical outcomes for patients. In particular, there are many
      challenges associated with the use of cell- and tissue-based products for
      clinical therapies. This review summarizes the transformation and global progress
      in translational medicine over the past decade. The current obstacles and
      opportunities in translational regenerative medicine are outlined in the context
      of stem cell therapy and tissue engineering for the safe and effective
      regeneration of functional tissue. This review highlights the requirement for
      multi-disciplinary and inter-disciplinary cooperation to ensure the development
      of the best possible regenerative therapies within the shortest timeframe
      possible for the greatest patient benefit.

PMID- 22138412
TI  - Microbial xylanases: engineering, production and industrial applications.
AB  - Enzymatic depolymerization of hemicellulose to monomer sugars needs the
      synergistic action of multiple enzymes, among them endo-xylanases (EC 3.2.1.8)
      and beta-xylosidases (EC 3.2.1.37) (collectively xylanases) play a vital role in
      depolymerizing xylan, the major component of hemicellulose. Recent developments
      in recombinant protein engineering have paved the way for engineering and
      expressing xylanases in both heterologous and homologous hosts. Functional
      expression of endo-xylanases has been successful in many hosts including
      bacteria, yeasts, fungi and plants with yeasts being the most promising
      expression systems. Functional expression of beta-xylosidases is more challenging
      possibly due to their more complicated structures. The structures of endo
      xylanases of glycoside hydrolase families 10 and 11 have been well elucidated.
      Family F/10 endo-xylanases are composed of a cellulose-binding domain and a
      catalytic domain connected by a linker peptide with a (beta/alpha)8 fold TIM
      barrel. Family G/11 endo-xylanases have a beta-jelly roll structure and are
      thought to be able to pass through the pores of hemicellulose network owing to
      their smaller molecular sizes. The structure of a beta-D-xylosidase belonging to
      family 39 glycoside hydrolase has been elucidated as a tetramer with each monomer
      being composed of three distinct regions: a catalytic domain of the canonical
      (beta/alpha)8--TIM barrel fold, a beta-sandwich domain and a small alpha-helical
      domain with the enzyme active site that binds to D-xylooligomers being present on
      the upper side of the barrel. Glycosylation is generally considered as one of the
      most important post-translational modifications of xylanases, but a few examples
      showed functional expression of eukaryotic xylanases in bacteria. The optimal
      ratio of these synergistic enzymes is very important in improving hydrolysis
      efficiency and reducing enzyme dosage but has hardly been addressed in
      literature. Xylanases have been used in traditional fields such as food, feed and
      paper industries for a longer time but more and more attention has been paid to
      using them in producing sugars and other chemicals from lignocelluloses in recent
      years. Mining new genes from nature, rational engineering of known genes and
      directed evolution of these genes are required to get tailor-made xylanases for
      various industrial applications.

PMID- 22138413
TI  - Estrogens promote proliferation of the seminoma-like TCam-2 cell line through a
      GPER-dependent ERalpha36 induction.
AB  - Seminoma, originated from carcinoma in situ cells (CIS), is one of the main
      causes of cancer in young men. Postpubertal development of these testicular germ
      cell tumors suggests a hormone-sensitive way of CIS cell proliferation induction.
      Using the unique seminoma TCam-2 cell line, we demonstrate that both estradiol
      and testosterone can stimulate TCam-2 cell proliferation in the absence of the
      estradiol receptor ERalpha. We establish that estradiol can activate GPER
      cAMP/PKA signalling pathway. TCam-2 cells express ERalpha36, a truncated isoform
      of the canonical ERalpha receptor, the expression of which is rapidly induced
      after estrogen treatment in a GPER-dependent manner. ERalpha36 knockdown
      indicates that ERalpha36 is (i) a downstream target of E(2)-activated
      GPER/PKA/CREB pathway, (ii) required for estradiol-dependent EGFR expression,
      (iii) necessary for cell proliferation. Colocalization of ERalpha36 with
      cytoskeleton microfilaments suggests a role of estrogens in cell motility. Our
      results highlight the functional role of ERalpha36 in context of seminoma cell
      proliferation and the importance of testing ERalpha36 in vivo as a possible
      future prognostic marker.

PMID- 22138414
TI  - Testosterone inhibits transforming growth factor-beta signaling during myogenic
      differentiation and proliferation of mouse satellite cells: potential role of
      follistatin in mediating testosterone action.
AB  - Testosterone (T) administration is associated with increased satellite cell
      number and skeletal muscle hypertrophy, although there is considerable
      heterogeneity in the response of different skeletal muscle groups to T in vivo.
      We investigated the effects of T on the growth and differentiation of satellite
      cells isolated from levator ani (LA) and gastrocnemius (gastroc) muscles. T up
      regulated follistatin (Fst) expression, but down regulated the mRNA and protein
      expression of a number of genes in the transforming growth factor-beta (TGF-beta)
      signaling pathway. Inhibition of Fst expression by small interfering RNA (siRNA)
      inhibited myogenic differentiation and blocked the pro-myogenic effects of T.
      Treatment of satellite cells with T or Fst up regulated the expression of Pax7
      and PCNA, and increased their proliferation. T and Fst blocked TGF-beta induced
      inhibition of growth and myogenic differentiation and down regulated TGF-beta
      dependent transcriptome in both LA and gastroc cells. We conclude that T
      stimulation of satellite cell proliferation and myogenic differentiation are
      associated with up regulation of Fst and inhibition of TGF-beta-signaling.

PMID- 22138415
TI  - Prospective comparison of new Japanese Association for Acute Medicine (JAAM) DIC
      and International Society of Thrombosis and Hemostasis (ISTH) DIC score in
      critically ill septic patients.
AB  - INTRODUCTION: We prospectively compared the new Japanese Association for Acute
      Medicine (JAAM) score with the International Society of Thrombosis and Hemostasis
      (ISTH) score for diagnosis of disseminated intravascular coagulation (DIC) in
      septic patients admitted in a general critical care intensive care unit. MATERIAL
      AND METHOD: Septic patients with platelet count of <150 * 10(9)/L were included.
      Both DIC scores were estimated from day 1 to day 4 along with APACHE II and SOFA
      scores. RESULTS: Out of the 148 blood samples drawn from 42 patients (28 male &
      14 female) the JAAM and ISTH DIC scores had an overall significant agreement
      (k=0.246, p<0.001) in 83 samples. JAAM score had higher diagnostic rates on all
      four days. Significant (p <= 0.001) day wise variation existed in JAAM and ISTH
      DIC scores. Correlation between JAAM DIC and ISTH DIC scores on day 1 (r=0.631) &
      day 4 (r=0.609) was significant (p<0.001). Pneumonia was the predominant cause of
      sepsis. Twenty seven (64.3%) patients died during their stay in ICU. Amongst DIC
      patients both severity scores (SOFA/APACHE II) and DIC scores (JAAM/ISTH) did not
      discriminate between survivors and non-survivors. Health care associated
      infection (p=0.040), high lactate levels (p=0.020) on day 1 and high
      procalcitonin levels (p=0.036) were found to have significant discriminating
      ability between survivors and non-survivors. Significantly shorter length of stay
      was observed amongst non-survivors (p=0.002). CONCLUSIONS: In sepsis the JAAM DIC
      score identified most of the patients diagnosed by the overt ISTH criteria, but
      failed to discriminate between survivors and non-survivors amongst DIC patients.

PMID- 22138416
TI  - Adipokine levels in subretinal fluid from patients with rhegmatogenous retinal
      detachment.
AB  - Adipokines have recently emerged as a novel group of mediators with important
      roles in inflammatory and immune responses and in the process of wound healing.
      This study investigated the involvement of several adipokines in the future
      development of proliferative vitreoretinopathy (PVR) following reattachment
      surgery for rhegmatogenous retinal detachment (RRD). A multiplex immunoassay was
      used to measure 6 different adipokines in 75 subretinal fluid samples collected
      during reattachment surgery for primary RRD. Twenty-one patients who developed a
      redetachment due to postoperative PVR after scleral buckling surgery (PVR group)
      were compared with age-, sex-, and storage-time-matched RRD samples from 54
      patients with an uncomplicated postoperative course (RRD group). Levels of
      adiponectin (P = 0.006), cathepsin S (P = 0.001), and leptin (P = 0.041) were
      significantly elevated in the PVR group as compared to the RRD group. Levels of
      tissue inhibitor of metalloproteinase (TIMP)-1 were significantly lower in the
      PVR group than in the RRD group (P = 0.044). After correction for diabetes, body
      mass index (BMI), macular involvement, and preoperative PVR, the association
      between postoperative PVR development and adiponectin, cathepsin S, and TIMP-1
      remained statistically significant (P < 0.05), whereas the significant
      correlation between PVR and elevated leptin levels was lost (P = 0.068). There
      were no significant differences in levels of chemerin (P = 0.351) and adipsin (P
      = 0.915). Of all adipokines investigated, multivariate logistic regression
      analysis showed that adiponectin was the exclusive predictor of the development
      of postoperative PVR after scleral buckling surgery (P = 0.003). Our findings
      indicate that, at the time of surgery for primary RRD, an altered expression of
      certain adipokines is associated with the future development of postoperative
      PVR.

PMID- 22138418
TI  - Focus on molecules: Phospholipase D.

PMID- 22138417
TI  - A novel ARMS2 splice variant is identified in human retina.

PMID- 22138419
TI  - Perception and action de-coupling in congenital amusia: sensitivity to task
      demands.
AB  - Theories that purport the existence of a distinct auditory action stream have
      received support from the finding that individuals with congenital amusia, a
      disorder of pitch perception, are able to reproduce the direction of a pitch
      change that they are unable to identify (Loui, Guenther, Mathys, & Schlaug,
      2008). Although this finding has proved influential in theorizing about the
      existence of an auditory action-stream, aspects of the original study warrant
      further investigation. The present report attempts to replicate the original
      study's findings across a sizeable cohort of individuals with amusia (n=14),
      obtaining action (production) and perception thresholds for pitch direction. In
      contrast to the original study, we find evidence of a double dissociation: while
      a minority of amusics had lower (better) thresholds for production compared to
      perception of pitch, more than half showed the reverse pattern. To explore the
      impact of task demands, perception thresholds were also measured using a two
      alternative, criterion-free, forced choice task that avoided labeling demands.
      Controls' thresholds were task-invariant while amusics' thresholds were
      significantly task-dependent. We argue that the direction and extent of a
      perception/production dissociation in this population reflects individual
      differences in the mapping of pitch representations to labels ("up"; "down") and
      to the vocal apparatus, as opposed to anything intrinsically yoked to perception
      or action per se.

PMID- 22138420
TI  - Comparable levels of folate-induced aneusomy in B-lymphoblasts from oral-cleft
      patients and controls.
AB  - BACKGROUND: Peri-conceptional use of folic acid contributes to protection against
      congenital malformations, such as neural tube defects and cleft lip with or
      without cleft palate (CL/P). Previous studies showed that low folate levels cause
      DNA damage, leading to chromosomal instability and aneusomy. This study seeks to
      confirm this finding and investigates whether the in vitro sensitivity towards
      aneusomy of chromosome 17 and 21 in the folate-deficient state differs between
      CL/P patients and controls. METHODS: Epstein-Barr virus-immortalized B
      lymphoblasts derived from 15 CL/P children and 15 controls, were cultured in
      medium with high and low concentrations - approximately 40nM and 5nM - of 5
      methyltetrahydrofolate, respectively. Fluorescence in situ hybridization was used
      to detect specific fluorescence signals for chromosomes 17 and 21. RESULTS: A
      significant increase in aneusomy of chromosomes 17 (2.3% vs 7.6%; p <= 0.001) and
      21 (2.5% vs 7.0%; p <= 0.001) was observed after 10 days of culturing in low
      folate. These results were comparable in cell lines from patients and controls.
      Interestingly, for chromosome 17 the folate deficiency mainly resulted in an
      increase of monosomy (6%, p <= 0.001), while for chromosome 21 the increase of
      trisomy was larger (4.9%, p <= 0.001). CONCLUSIONS: These data suggest that
      folate deficiency is a significant risk factor in the development of aneusomy and
      may affect the distribution of chromosomes during cell division. The comparable
      aneusomy frequencies in CL/P and in controls suggest that other folate-related
      processes are involved in the pathogenesis of CL/P, and additional investigations
      are needed to identify the causal mechanisms.

PMID- 22138421
TI  - Influence of immunization with non-genotoxic PAH-KLH conjugates on the resistance
      of organisms exposed to benzo(a)pyrene.
AB  - Polycyclic aromatic hydrocarbons (PAH) are recognized as common environmental
      pollutants released into the environment from many natural as well as man-made
      sources, and some have been classified as potent carcinogens. The main
      representative of the carcinogenic PAH is benzo(a)pyrene (B(a)P) which is known
      to induce genotoxic effects in vitro and in vivo, detected as PAH-DNA adducts.
      Long-term PAH exposure may be accompanied by an immunological response with the
      formation of antibodies against PAH as well as against PAH-DNA adducts. This
      paper describes the use of four PAH-keyhole-limpet haemocyanin (KLH) conjugates
      for the induction of specific and cross-reactive anti-PAH antibodies and focuses
      on the potential protective effects of anti-PAH antibodies produced after
      immunization of mice. In the in vitro experiments with HepG-2 cells, the
      genotoxicity of the PAH-KLH conjugates and the neutralizing effect of induced
      anti-PAH antibodies were evaluated. The titer of specific anti-PAH antibodies in
      sera and the amounts of DNA adducts in liver homogenates from immunized mice were
      investigated in vivo. The results show that anti-PAH antibodies of class IgG were
      induced during immunization. All the PAH-KLH conjugates tested were non-genotoxic
      and did not induce detectable DNA adducts in HepG2 cells or in the liver of
      immunized mice. The results show that only B(a)P-specific and B(a)P cross
      reactive antibodies are able to neutralize B(a)P or its activated metabolites,
      which was revealed by a sudden decrease in the titer of anti-B(a)P antibodies in
      mouse sera after exposure to B(a)P. Furthermore, the anti-B(a)P antibodies
      produced by immunization were effective in reducing the amount of DNA adducts in
      mouse livers after intraperitoneal (i.p.) exposure to B(a)P. The results suggest
      that immunization with PAH-KLH conjugates can protect organisms against the
      adverse effects of carcinogenic PAH.

PMID- 22138422
TI  - Genotoxicity of silver nanoparticles evaluated using the Ames test and in vitro
      micronucleus assay.
AB  - Silver nanoparticles (AgNPs) have antimicrobial properties, which have
      contributed to their widespread use in consumer products. A current issue
      regarding nanomaterials is the extent to which existing genotoxicity assays are
      useful for evaluating the risks associated with their use. In this study, the
      genotoxicity of 5 nm AgNPs was assessed using two standard genotoxicity assays,
      the Salmonella reverse mutation assay (Ames test) and the in vitro micronucleus
      assay. Using the preincubation version of the Ames assay, Salmonella strains
      TA102, TA100, TA1537, TA98, and TA1535 were treated with 0.15-76.8 MUg/plate of
      the AgNPs. Toxicity limited the doses that could be assayed to 2.4-38.4
      MUg/plate; no increases in mutant frequency over the vehicle control were found
      for the concentrations that could be assayed. Human lymphoblastoid TK6 cells were
      treated with 10-30 MUg/ml AgNPs, and additional cells were treated with water and
      0.73 gy X-rays as vehicle and positive controls. Micronucleus frequency was
      increased by the AgNP treatment in a dose-dependent manner. At a concentration of
      30 MUg/ml (with 45.4% relative population doubling), AgNPs induced a significant,
      3.17-fold increase with a net increase of 1.60% in micronucleus frequency over
      the vehicle control, a weak positive response by our criteria. These results
      demonstrate that the 5 nm AgNP are genotoxic in TK6 cells. Also, the data suggest
      that the in vitro micronucleus assay may be more appropriate than the Ames test
      for evaluating the genotoxicity of the AgNPs.

PMID- 22138423
TI  - Nitrite and nitrate reduction by molybdenum centers of the nitrate reductase
      type: computational predictions on the catalytic mechanism.
AB  - Nitrate reductases (NRs) are enzymes that catalyze reduction of nitrate to
      nitrite using a molybdenum cofactor. In an alternative reaction, plant NRs have
      also been shown to catalyze reduction of nitrite to nitric oxide, and this
      appears to be a major source of nitric oxide synthesis in plants, although other
      pathways have also been shown. Here, density functional theory (DFT) results are
      shown, indicating that although nitrate is thermodynamically the preferred
      substrate for the NR active site, both nitrite and nitrate are easily reduced to
      nitrite and NO, respectively. These mechanisms require a Mo(IV) state.
      Additionally, in the case of the nitrite, linkage isomerism is at work and
      controlled by the metal oxidation state, and reduction is, unlike in the nitrate
      case, dependent on protonation. The data may be relevant to other molybdenum
      enzymes with similar active sites, such as xanthine oxidase.

PMID- 22138424
TI  - Solitary atrial myocardial metastasis revealing ileal neuroendocrine carcinoma.
AB  - A previously healthy 56-year-old man presented with chest pain. Echocardiography
      and cardiac magnetic resonance imaging revealed minimal pericardial effusion
      associated with an isolated myocardial mass, protruding into the left atrium. The
      tumor was surgically removed. Cardiac valve morphology was strictly normal.
      Histology revealed a well-differentiated neuroendocrine carcinoma. Positron
      emission tomography scan and thin-slice abdominal computed tomography
      demonstrated ileal tumor, without evidence of liver metastasis. Histological
      study of the removed ileal tumor confirmed a neuroendocrine carcinoma, and
      histology of liver biopsy was negative. Somatostatin analogue treatment was
      started. No tumoral recurrence was observed after 1 year of follow-up. In
      conclusion, we report an unusual presentation of neuroendocrine carcinoma,
      revealed by a large solitary atrial metastasis, in the absence of liver
      involvement or carcinoid syndrome.

PMID- 22138425
TI  - Modern device technologies.
AB  - Implantable cardiac devices for arrhythmias and related conditions are a rapidly
      evolving field, with a constant stream of technologies being developed. There are
      a number of novel devices, other than conventional pacemakers and implantable
      defibrillators, currently being developed that have the potential to greatly
      improve patient outcomes. This paper reviews the important recent technologies,
      the subcutaneous defibrillator, cardiac contraction modulation, the HeartPOD and
      CardioMEMS heart failure monitors, left atrial appendage closure devices and
      leadless cardiac pacing. The features of these devices, the results to date, and
      their possible clinical utility are discussed.

PMID- 22138426
TI  - Physiologic partograph to improve birth safety and outcomes among low-risk,
      nulliparous women with spontaneous labor onset.
AB  - Oxytocin augmentation and cesarean rates among low-risk, term, nulliparous women
      with a spontaneous onset of labor in the United States approximate 50% and 26.5%,
      respectively. This indicates that the quality of obstetrical care is less than
      optimal in this nation. Exorbitant oxytocin use, the intervention most commonly
      associated with preventable adverse perinatal outcomes, jeopardizes birth safety
      while the high cesarean rate in this high-volume group compromises population
      health and increases health care costs. Dystocia, characterized by the slow,
      abnormal progression of labor, is the most commonly reported indication for
      primary cesareans, accounting directly for approximately 50% of all nulliparous
      cesareans and indirectly for most repeat cesareans. Diagnoses of dystocia are
      most often based on ambiguously defined delays in cervical dilation beyond which
      labor augmentation is deemed justified. Dystocia is known to be over-diagnosed
      which undoubtedly contributes to contemporary oxytocin augmentation and primary
      cesarean rates. Labor attendants would benefit from an evidence-based framework
      for homogenous labor assessment. To this end, we present a physiologically-based
      partograph for 'in-hospital' use in assessing the labors of low-risk, term,
      nulliparous women with spontaneous labor onset. This tool incorporates several
      evidence-based labor principles that combine to give needed clinical meaning to
      'dystocia' as a diagnosis. It is hypothesized that our partograph will safely
      limit diagnoses of dystocia to only the slowest 10% of low-risk, nulliparous
      women. This should, in turn, safe-guard against unnecessary, injudicious, and
      potentially harmful use of oxytocin when labor is already adequately progressing
      while also indicating when its use may be justified. We further hypothesize that
      cesareans performed for dystocia in this population will decrease by >= 50%. No
      significant influence on other labor process or labor outcome variables is
      expected with partograph use. Widespread use of this physiologically-based
      partograph will be warranted if our hypotheses are supported.

PMID- 22138428
TI  - Theaflavin, a black tea polyphenol, protects nigral dopaminergic neurons against
      chronic MPTP/probenecid induced Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder,
      characterized by loss of dopominergic neurons in substantia nigra pars compacta,
      and can be experimentally induced by the neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6
      tetrahydropyridine (MPTP). Chronic administration of MPTP/probenecid (MPTP/p)
      leads to oxidative stress, induction of apoptosis, and loss of dopominergic
      neurons which results in motor impairments. Epidemiological studies have shown an
      inverse relationship between tea consumption and susceptibility to PD. Theaflavin
      is a black tea polyphenol, which possess a wide variety of pharmacological
      properties including potent anti oxidative, anti apoptotic and anti inflammatory
      effects. The current study is aimed to assess the effect of theaflavin against
      MPTP/p induced neurodegenaration in C57BL/6 mice. We found that the theaflavin
      attenuates MPTP/p induced apoptosis and neurodegeneration as evidenced by
      increased expression of nigral tyrosine hydroxylase (TH), dopamine transporter
      (DAT) and reduced apoptotic markers such as caspase-3, 8, 9 accompanied by
      normalized behavioral characterization. This may be due to anti oxidative and
      anti apoptotic activity and these data indicate that theaflavin may provide a
      valuable therapeutic strategy for the treatment of progressive neurodegenerative
      diseases such as PD.

PMID- 22138427
TI  - Frontoparietal connectivity in substance-naive youth with and without a family
      history of alcoholism.
AB  - Frontoparietal connections underlie key executive cognitive functions.
      Abnormalities in the frontoparietal network have been observed in chronic
      alcoholics and associated with alcohol-related cognitive deficits. It remains
      unclear whether neurobiological differences in frontoparietal circuitry exist in
      substance-naive youth who are at-risk for alcohol use disorders. This study used
      functional connectivity magnetic resonance imaging and diffusion tensor imaging
      to examine frontoparietal connectivity and underlying white matter microstructure
      in 20 substance-naive youth with a family history of alcohol dependence and 20
      well-matched controls without familial substance use disorders. Youth with a
      family history of alcohol dependence showed significantly less functional
      connectivity between posterior parietal and dorsolateral prefrontal seed regions
      (ps<.05), as compared to family history negative controls; however, they did not
      show differences in white matter architecture within tracts subserving
      frontoparietal circuitry (ps>.34). Substance-naive youth with a family history of
      alcohol dependence show less frontoparietal functional connectivity in the
      absence of white matter microstructural abnormalities as compared to youth with
      no familial risk. This may suggest a potential neurobiological marker for the
      development of substance use disorders.

PMID- 22138429
TI  - Neurotensin induced Egr-1 activity is altered in the postpartum period in mice.
AB  - Neurotensin (NT) is a 13 amino acid neuropeptide that is identical in mice and
      humans and is released from and acts upon a number of social brain regions.
      Recent work indicates NT neurotransmission may be altered in postpartum females
      and support the onset of some maternal behaviors. In a recent study, we
      highlighted how virgin and postpartum brains from mice selected for high
      offspring protection differ in response to injected NT (0.1 MUg) relative to
      vehicle when examining c-Fos profiles across the CNS. In this companion study we
      use a second marker for brain activity, Egr-1, and evaluate multiple brain
      regions. Common significant increased Egr-1 responses to NT (relative to vehicle)
      were found in both female groups only in ventromedial hypothalamus. In lateral
      periaqueductal gray, virgin mice showed a significant Egr-1 increase with NT
      (relative to vehicle), but maternal mice did not. When comparing NT injections,
      virgin (relative to maternal) mice had significantly higher activity in five
      regions, including anterior hypothalamus, lateral hypothalamus, somatosensory
      cortex, paraventricular nucleus, and zona incerta; no regions were higher in
      maternal mice. A Principal Components Analysis was also used for data mining and
      in virgin mice, greater changes in activity hubs were found with NT (relative to
      vehicle) than for maternal mice. Overall, a lower sensitivity to NT in terms of
      Egr-1 reactivity in the maternal state was highlighted and this is consistent
      with previous c-Fos results. These findings provide additional insight into the
      mechanisms by which NT functions in the CNS.

PMID- 22138430
TI  - Aquaporin-4 immunoreactivity in Muller and amacrine cells of marine teleost fish
      retina.
AB  - Aquaporins (AQPs) are membrane proteins that facilitate water transport across
      biological membranes and are essential for the proper function of neural tissue.
      Although AQPs have been extensively studied in mammalian retina, their presence
      in lower vertebrate retina is less frequently characterized. AQP4 expressed in
      mammalian and chick Muller cells plays a major part in maintaining retinal
      homeostasis. In this study, we examined the immunoreactivity of AQP4 in the adult
      retina of gilthead sea bream (Sparus aurata-teleost fish), during light and dark
      adaptation. The AQP4 expression was detected in Muller cell somas at the inner
      nuclear layer and in the end-feet processes near the vitreoretinal border.
      Moreover, AQP4 was also evident in cone photoreceptor cells and in a GABAergic
      subpopulation of amacrine cells (AQP4-ACs). Four different types of AQP4-ACs were
      characterized based on their morphology and dendrite stratification.
      Interestingly, a stronger AQP4 immunoreactivity was observed in the inner nuclear
      layer during dark adaptation, accompanied by a significant increment in AQP4-ACs
      cell size. Hence, AQP4 may play an important role in water distribution in the
      teleost fish retina.

PMID- 22138431
TI  - Electrophysiological correlates of verbal and tonal working memory.
AB  - The present study's basic research question concerns differences in the
      processing of verbal and tonal stimuli in working memory. Participants had to
      rehearse sequences containing tonal and verbal information and to decide whether
      a subsequently presented probe stimulus belonged to the previously presented
      sequence. Electrophysiological measures were taken and analysed with regard to
      local (event-related potentials, ERP) and global (microstates) aspects. A larger
      N400 amplitude occurred for new compared to old items in the verbal, but not the
      tonal condition. The microstate analysis revealed differences in the specificity
      of several microstates for old compared to new items in the tonal and the verbal
      working memory condition. Corroborating previous results, the present study
      reveals differences in the efficiency of working memory processes for tonal
      compared to verbal stimuli with processes being more capable for the verbal
      compared to the tonal condition.

PMID- 22138432
TI  - Evaluation of the patient undergoing respiratory endoscopic procedures.
AB  - Endoscopic techniques can be considered reasonably safe since they are widely
      used and the rate of complications is extremely low. Still complications do occur
      and in order to avoid them, the evaluation of the patient before and after any
      intervention is of the utmost importance. In this article, issues concerning the
      preparation of the patient and informed consent, the general assessment - medical
      history, current medications, physical examination, laboratory tests,
      radiological evaluation and analysis of the indication and planning will be
      addressed. The post intervention evaluation will also be discussed, in order to
      detect and treat complications and decide on the final guidance for the patient
      after discharge. There are very few up-to-date studies or publications dealing
      with these areas, the evidence level remains low and most recommendations are
      based on common sense and expert opinion.

PMID- 22138433
TI  - Cost estimation for solid waste management in industrialising regions-
      precedents, problems and prospects.
AB  - The importance of cost planning for solid waste management (SWM) in
      industrialising regions (IR) is not well recognised. The approaches used to
      estimate costs of SWM can broadly be classified into three categories - the unit
      cost method, benchmarking techniques and developing cost models using sub
      approaches such as cost and production function analysis. These methods have been
      developed into computer programmes with varying functionality and utility. IR
      mostly use the unit cost and benchmarking approach to estimate their SWM costs.
      The models for cost estimation, on the other hand, are used at times in
      industrialised countries, but not in IR. Taken together, these approaches could
      be viewed as precedents that can be modified appropriately to suit waste
      management systems in IR. The main challenges (or problems) one might face while
      attempting to do so are a lack of cost data, and a lack of quality for what data
      do exist. There are practical benefits to planners in IR where solid waste
      problems are critical and budgets are limited.

PMID- 22138434
TI  - Delta9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus
      monkeys.
AB  - BACKGROUND: Cannabis is commonly consumed by Ecstasy (3,4
      methylenedioxymethamphetamine; MDMA) users, including as an intentional strategy
      to manipulate the drug experience. The most active psychoactive constituent in
      cannabis, Delta(9)-tetrahydrocannabinol (THC), and other drugs with partial or
      full agonist activity at the CB(1) receptor, produces a reduction of body
      temperature in rodents. Reports show that administration of THC can attenuate
      temperature increases caused by MDMA in mice or rats; however, a recent study in
      humans shows that THC potentiates MDMA-induced temperature elevations. Relatively
      little scientific evidence on the thermoregulatory effects of THC in monkeys is
      available. METHODS: The body temperature of male rhesus macaques was recorded
      after challenge with THC (0.1-0.3 mg/kg, i.m.) or combined challenge of THC with
      the CB(1) receptor antagonist SR141716 (Rimonabant; 0.3 mg/kg, i.m.) or combined
      challenge of THC (0.1, 0.3 mg/kg, i.m.) with MDMA (1.78 mg/kg p.o.) using
      minimally-invasive, implanted radiotelemetry techniques. RESULTS: THC reduced the
      body temperature of monkeys in a dose-dependent manner with the nadir observed 3
      5 h post-injection; however, an attenuation of normal circadian cooling was also
      produced overnight following dosing. Hypothermia induced by THC (0.3 mg/kg, i.m.)
      was prevented by Rimonabant (0.3 mg/kg, i.m.). Finally, 0.3 mg/kg THC (i.m.)
      attenuated the elevation of body temperature produced by MDMA for about 4 h after
      oral dosing. CONCLUSIONS: As with rodents THC produces a robust and lasting
      decrement in the body temperature of rhesus monkeys; this effect is mediated by
      the CB(1) receptor. THC also protects against the immediate hyperthermic effects
      of MDMA in monkeys in a dose-dependent manner. Nevertheless, a paradoxical
      attenuation of circadian cooling overnight after the THC/MDMA combination
      cautions that longer-term effects may be critical in assessing risks for the
      recreational user of cannabis in combination with MDMA.

PMID- 22138435
TI  - Targeting Bcl-2 family proteins in adult T-cell leukemia/lymphoma: in vitro and
      in vivo effects of the novel Bcl-2 family inhibitor ABT-737.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by
      human T-lymphotropic virus type I (HTLV-1). ABT-737, a small molecule inhibitor
      of Bcl-2, Bcl-X(L), and Bcl-w, significantly induced apoptosis in HTLV-1 infected
      T-cell lines as well as in fresh ATLL cells, and synergistically enhanced the
      cytotoxicity and apoptosis induced by conventional cytotoxic drugs. Moreover, ABT
      737 significantly inhibited the in vivo tumor growth of an ATLL mouse model.
      These results suggest that the use of an agent targeting anti-apoptotic bcl-2
      family proteins, either alone or in combination with other conventional drugs,
      represents a novel promising approach for ATLL.

PMID- 22138436
TI  - Combinational therapy: new hope for pancreatic cancer?
AB  - Pancreatic cancer is a devastating disease with a low overall survival rate.
      Chemotherapy is the most common treatment for patients presenting with advanced
      pancreatic cancer. Gemcitabine achieves a modest improvement in overall survival
      and is the gold standard for advanced pancreatic cancer treatment. Capecitabine
      and S-1, derivatives of 5-fluorouracil (5-FU), offers minimal clinical benefits.
      Folfirinox represents a new and aggressive regimen that might benefit patients of
      metastatic pancreatic cancer with good performance status. Other chemotherapy
      drugs such as platinums and irinotecan do not provide significant improvement in
      overall survival, but have been used as part of combinational therapies.
      Comparing to systemically delivered chemotherapy, regional intra-arterial
      chemotherapy achieves higher local drug concentration in tumors with lower
      systemic drug toxicity, and may serve as a better treatment regimen. Although
      there have been progress made in chemotherapeutic strategies against pancreatic
      cancer, the overall survival is not significantly improved in the last decade.
      Recently, development of chemotherapy in combination with molecular targeted
      therapies holds great promise in pancreatic cancer treatment, especially in
      patients with metastatic disease. Growing bodies of preclinical and clinical
      evidences indicate that the combination of conventional modalities with specific
      molecular targeted therapy increase the efficacy of the monotherapy without an
      increase in toxicity. In this review, we summarized the current regimens of
      chemotherapy and molecular targeted therapy for advanced pancreatic cancer and
      highlighted the novel combinational treatments tested in recent clinical trials.

PMID- 22138437
TI  - 3D intersegmental knee loading in below-knee amputees across steady-state walking
      speeds.
AB  - BACKGROUND: Unilateral below-knee amputees often develop comorbidities that
      include knee joint disorders (e.g., intact leg knee osteoarthritis), with the
      mechanisms leading to these comorbidities being poorly understood. Mechanical
      knee loading of non-amputees has been associated with joint disorders and shown
      to be influenced by walking speed. However, the relationships between amputee
      knee loading and speed have not been identified. This study examined three
      dimensional mechanical knee loading of amputees across a wide range of steady
      state walking speeds. METHODS: Fourteen amputees and 10 non-amputee control
      subjects were analyzed at four overground walking speeds. At each speed,
      intersegmental joint moment and force impulses (i.e., time-integrals over the
      stance phase) were compared between the control, intact and residual knees using
      repeated-measures ANOVAs. FINDINGS: There were no differences in joint force
      impulses between the intact and control knees. The intact knee abduction moment
      impulse was lower than the non-amputees at 0.6 and 0.9 m/s. The intact knee
      flexion moment impulses at 0.6, 1.2 and 1.5m/s and knee external rotation moment
      impulses at all speeds were greater than the residual knee. The residual knee
      extension moment and posterior force impulses were insensitive to speed
      increases, while these quantities increased in intact and control knees.
      INTERPRETATION: These results suggest the intact knees of asymptomatic and
      relatively new amputees are not overloaded during walking compared to non
      amputees. Increased knee loads may develop in response to prolonged prosthesis
      usage or joint disorder onset. Further study is needed to determine if the
      identified bilateral loading asymmetries across speeds lead to diminished knee
      joint health.

PMID- 22138438
TI  - Infection study of Bombyx mori macula-like virus (BmMLV) using a BmMLV-negative
      cell line and an infectious cDNA clone.
AB  - Previously, a novel macula-like virus was identified from Bombyx mori cultured
      cell line BmN and termed B. mori macula-like virus (BmMLV). BmMLV encodes a 6.5
      kb-long positive, single-strand RNA genome, which contains putative RNA-dependent
      RNA polymerase (RdRp), coat protein (cp) and p15 genes. In this study, CP
      expression in several B. mori-derived cell lines was examined by using the CP
      antibody. Surprisingly, Western blot analysis revealed that all of the cell lines
      tested have already been infected with BmMLV. To perform reverse genetic studies
      in BmMLV, a new BmMLV-negative cell line, designated as BmVF from the embryos of
      B. mori was established. Infection studies showed that BmVF cells were permissive
      to BmMLV persistent infection. In addition, a full-length infectious cDNA clone
      of BmMLV, termed pHMLV was developed. Upon transfection of pHMLV into BmMLV
      negative BmVF cells, viral CP was detected in both cells and conditioned medium.
      When the cDNA-derived virus in conditioned medium was inoculated onto BmVF cells,
      efficient propagation of BmMLV was observed. Collectively, these results indicate
      that the new BmMLV-negative cell line and the infectious cDNA clone of BmMLV will
      be useful for elucidation of the mechanism of BmMLV replication and the
      functional roles of BmMLV genes.

PMID- 22138439
TI  - Evaluation of the celite secondary concentration procedure and an alternate
      elution buffer for the recovery of enteric adenoviruses 40 and 41.
AB  - The effective recovery of adenovirus from water is a critical first step in
      developing a virus occurrence method able to provide accurate data for risk
      assessments and other applications. During virus concentration, electropositive
      filters are typically eluted with beef extract, undergo secondary concentration
      using either an organic flocculation or polyethylene glycol (PEG) precipitation
      technique and are ultimately resuspended in sodium phosphate buffer. In this
      study, an alternative secondary concentration procedure using celite was
      optimized by identifying the optimal celite and elution buffer to use. Two
      elution buffers, sodium phosphate and 1* PBS, were evaluated for their impact on
      real-time PCR. Sodium phosphate produced high levels of PCR inhibition compared
      to 1* PBS and so 1* PBS was used in subsequent experiments. The two secondary
      concentration techniques that were tested with adenovirus 40 and 41 gave
      recoveries of 69% and 65% for the optimized celite method and 75% and 109% for
      the organic flocculation method, respectively. Fine particle, calcinated celites
      in combination with 1* PBS elution buffer were shown to be effective at
      concentrating adenovirus 40 and 41 during secondary concentration and their
      subsequent detection using PCR. Heat extraction efficiencies were compared to
      samples processed using a DNA extraction kit to address possible virus
      aggregation issues. Samples processed through DNA extraction were found to
      produce realistic adenovirus recoveries compared to exaggerated recoveries using
      heat extraction.

PMID- 22138440
TI  - Does cellular aging relate to patterns of allostasis? An examination of basal and
      stress reactive HPA axis activity and telomere length.
AB  - Long-term exposure to stress and its physiological mediators, in particular
      cortisol, may lead to impaired telomere maintenance. In this study, we examine if
      greater cortisol responses to an acute stressor and/or dysregulated patterns of
      daily cortisol secretion are associated with shorter telomere length. Twenty
      three postmenopausal women comprising caregivers for dementia partners (n=14) and
      age- and BMI-matched non-caregivers provided home sampling of cortisol-saliva
      samples at waking, 30 min after waking, and bedtime, and a 12-hour overnight
      urine collection. They were also exposed to an acute laboratory stressor
      throughout which they provided saliva samples. Peripheral blood mononuclear cells
      were isolated from a fasting blood sample and assayed for telomere length. As
      hypothesized, greater cortisol responses to the acute stressor were associated
      with shorter telomeres, as were higher overnight urinary free cortisol levels and
      flatter daytime cortisol slopes. While robust physiological responses to acute
      stress serve important functions, the long-term consequences of frequent high
      stress reactivity may include accelerated telomere shortening.

PMID- 22138441
TI  - X-ray kinematics analysis of vaginal scent marking in female Syrian hamsters
      (Mesocricetus auratus).
AB  - Vaginal marking is a stereotyped scent marking behavior in female Syrian hamsters
      used to attract male hamsters for mating. Although the modulation of vaginal
      marking by hormones and odors is well understood, the motor control of this
      proceptive reproductive behavior remains unknown. Therefore, we used X-ray
      videography to visualize individual bone movements during vaginal marking.
      Kinematic analyses revealed several consistent motor patterns of vaginal marking.
      Despite exhibiting a diversity of trial-to-trial non-marking behaviors (e.g.
      locomotor stepping), we found that lowering and raising the pelvis consistently
      corresponded with coordinated flexion and extension cycles of the hip, knee, and
      tail, suggesting that these movements are fundamental to vaginal marking
      behavior. Surprisingly, we observed only small changes in the angles of the
      pelvic and sacral regions, suggesting previous reports of pelvic rotation during
      vaginal marking may need to be reconsidered. From these kinematic data, we
      inferred that vaginal marking is primarily due to the actions of hip and knee
      extensor muscles of the trailing leg working against gravity to support the
      weight of the animal as it controls the descent of the pelvis to the ground. The
      cutaneous trunci muscle likely mediates the characteristic flexion of the tail.
      Interestingly, this tail movement occurred on the same time scale as the joint
      kinematics suggesting possible synergistic recruitment of these muscle groups.
      These data therefore provide new targets for future studies examining the
      peripheral control of female reproductive behaviors.

PMID- 22138442
TI  - Effects of the muscarinic agonist pilocarpine on vigilance states and locomotor
      activity in ring doves.
AB  - Cholinergic systems play a significant role in regulating a variety of behavioral
      functions in mammals and birds. The aim of this work is to study the effects of
      the muscarinic agonist pilocarpine on behavioral states by visual inspection and
      electroencephalographic recording; also, locomotor activity was continuously
      recorded by infrared interruption system in ring doves. The current results in
      birds demonstrated that the muscarinic agonist pilocarpine (1 and 3mg/kg, i.p.)
      primarily induced theta activity in addition to promote passive waking, while
      diminished active waking, the EEG slow wave rhythm and REM sleep in ring doves.
      The locomotor activity recorded continuously in ring doves diminished after
      pilocarpine treatment, which was in good agreement with the observed reduction of
      active waking derived of the EEG study. Altogether, the current results are
      similar to the effects of pilocarpine previously reported in mammals. In
      conclusion, hippocampal theta rhythm in birds suggests that this rhythm is an
      ancestral property of hippocampal function and similar cholinergic mechanisms
      regulate vigilance states and theta generation in mammals and birds.

PMID- 22138443
TI  - Contracaecum rudolphii B: gene content, arrangement and composition of its
      complete mitochondrial genome compared with Anisakis simplex s.l.
AB  - In the present study, we sequenced the complete mt genome (14,022 bp) of
      parasitic nematode Contracaecum rudolphii B and its structure and organization
      compared with Anisakis simplex s.l. The mt genome of C. rudolphii B is slightly
      longer than that of A. simplex s.l. (13,916 bp). C. rudolphii B mt genome is
      circular, and consists of 36 genes, including 12 genes for proteins, 2 genes for
      rRNA and 22 genes for tRNA. This genome contains a high A+T (70.5%) content. The
      mt gene order for C. rudolphii B is the same as those for A. simplex s.l., but it
      is distinctly different from other nematodes compared. The start codons inferred
      in the mt genome of C. rudolphii B are TTG and ATT. Six protein-coding genes use
      TAA as a stop codon whereas five genes use T and one genes use TAG as a
      termination codon. This pattern of codon usage reflects the strong bias for A and
      T in the mt genome of C. rudolphii B. Phylogenetic analyses using concatenated
      amino acid sequences of the 12 protein-coding genes, with three different
      computational algorithms (Bayes, ML and MP), all revealed distinct groups with
      high statistical support, indicating that C. rudolphii B and A. simplex s.l. is
      distinct but closely related species. These data provide additional novel mtDNA
      markers for studying the molecular epidemiology and population genetics of the C.
      rudolphii B, and should have implications for the molecular diagnosis, prevention
      and control of anisakidosis in humans and animals.

PMID- 22138444
TI  - Attrition and adherence of young women to aerobic exercise: lessons from the
      WISER study.
AB  - The purpose of this report is to identify factors associated with attrition and
      adherence of young women to a 16-week randomized aerobic exercise intervention on
      biomarkers associated with breast cancer risk. The exercise group was prescribed
      a progressive weight-bearing aerobic exercise program consisting of 30 minute
      workouts, 5 times/wk for 16 weeks. Adherence was calculated as the average
      minutes of exercise per week during participation in the study. Of the total of
      212 women randomized into the exercise intervention 46 dropped out, of which
      82.5% dropped out during the earlier stages of exercise suggesting that reasons
      for withdrawal may have been related to difficulties with initiating physical
      activity. Time commitment or lack of time was the primary reason for withdrawal.
      Drop outs reported lower physical activity at baseline than study completers
      (p=.0007). Although 78% of the 212 randomized participants completed the exercise
      intervention, only 4.7% of the participants exercised for at least 150 min/wk
      during the entire study period. Significant predictors of adherence were self
      reported physical activity at baseline and depression scores. We conclude that
      predictors of adherence to exercise in our population of young women are similar
      to those reported for older adults. We also found that young women are more
      likely to exercise at moderate to vigorous intensity for 90 to 120 min rather
      than 150 min per week, even when participating in a highly structured exercise
      intervention.

PMID- 22138445
TI  - The role of glutathione in brain tumor drug resistance.
AB  - Chemotherapy is central to the current treatment modality for primary human brain
      tumors, but despite high-dose and intensive treatment regimens there has been
      little improvement in patient outcome. The development of tumor chemoresistance
      has been proposed as a major contributor to this lack of response. While there
      have been some improvements in our understanding of the molecular mechanisms
      underlying brain tumor drug resistance over the past decade, the contribution of
      glutathione (GSH) and the GSH-related enzymes to drug resistance in brain tumors
      have been largely overlooked. GSH constitutes a major antioxidant defense system
      in the brain and together with the GSH-related enzymes plays an important role in
      protecting cells against free radical damage and dictating tumor cell response to
      adjuvant cancer therapies, including irradiation and chemotherapy. Glutamate
      cysteine ligase (GCL), glutathione synthetase (GS), glutathione peroxidase (GPx),
      glutathione reductase (GR), glutathione-S-transferases (GST), and GSH complex
      export transporters (GS-X pumps) are major components of the GSH-dependent enzyme
      system that function in a dynamic cascade to maintain redox homeostasis. In many
      tumors, the GSH system is often dysregulated, resulting in a more drug resistant
      phenotype. This is commonly associated with GST-mediated GSH conjugation of
      various anticancer agents leading to the formation of less toxic GSH-drug
      complexes, which can be readily exported from the cell. Advances in our
      understanding of the mechanisms of drug resistance and patient selection based on
      biomarker profiles will be crucial to adapt therapeutic strategies and improve
      outcomes for patients with primary malignant brain tumors.

PMID- 22138446
TI  - Hsp90 inhibitors sensitise human colon cancer cells to topoisomerase I poisons by
      depletion of key anti-apoptotic and cell cycle checkpoint proteins.
AB  - Hsp90 and topoisomerase I are both targets for chemotherapeutic agents.
      Topoisomerase I poisons are standard clinical treatments, whilst Hsp90 inhibitors
      are progressing through clinical trials. We have demonstrated that when an Hsp90
      inhibitor and topoisomerase I poison are combined they produce a synergistic
      increase in apoptosis in both p53+/+ and p53-/- HCT116 human colon cancer cells.
      Lack of p53 is associated with an increase in sensitivity to the combination
      treatment; p53+/+ cells treated with the topoisomerase I poison topotecan (TPT)
      arrest at G2, whereas in p53-/- cells the additional presence of the Hsp90
      inhibitor geldanamycin (GA) selectively abrogates the G2M checkpoint. More
      importantly we report that there is a common underlying p53-independent mechanism
      behind the observed synergistic combined drug effect. We show that concurrent
      treatment with GA and TPT is able to reverse TPT induced up-regulation of the
      anti-apoptotic protein Bcl2 in both p53+/+ and p53-/- HCT116 cells. The data
      suggests that inhibition of Hsp90 mediates down-regulation of Bcl2 following the
      combination treatment and cause a synergistic increase in apoptosis in both
      p53+/+ and p53-/- HCT116 cells; p53-/- HCT116 cells are more sensitive to the
      treatment because they also fail to arrest at G2 in the cell cycle.

PMID- 22138447
TI  - Corrector-mediated rescue of misprocessed CFTR mutants can be reduced by the P
      glycoprotein drug pump.
AB  - The most common cause of cystic fibrosis is deletion of Phe508 in the first
      nucleotide-binding domain (NBD) of the CFTR chloride channel, which inhibits
      protein folding. DeltaF508 CFTR can be rescued by indirect approaches such as low
      temperature but the protein is unstable. Here, we tested our predictions that (1)
      other CFTR mutants such V232D and H1085R were more stable at the cell surface
      than DeltaF508 CFTR after low temperature rescue and (2) the advantages of rescue
      with specific correctors (pharmacological chaperones) are that they may stabilize
      DeltaF508 CFTR and increase the effectiveness of the correctors by bypassing drug
      pumps such as P-glycoprotein (P-gp) (increased bioavailability). It was found
      that the stability of mutants V232D and H1085R after low-temperature (30 degrees
      C) rescue was about 10-fold higher than DeltaF508 CFTR. We show that the
      corrector, 4,5,7-trimethyl-N-phenylquinolin-2-amine (5a), could stabilize
      DeltaF508 CFTR at the cell surface. Unlike most correctors, corrector 5a showed
      specificity for CFTR as it did not rescue the G268V P-gp processing mutant nor
      stimulate the ATPase activity of wild-type P-gp. By contrast, corrector KM11060
      was a P-gp substrate as it stimulated P-gp ATPase activity and rescued the G268V
      mutant. Expression of wild-type P-gp reduced the effectiveness of CFTR rescue by
      corrector KM11060 by about 5-fold. The results underlie the importance of
      selecting correctors that are specific for CFTR because their efficiency can be
      reduced by drug pumps such as P-gp.

PMID- 22138448
TI  - The use of transgenic mouse models to reveal the functions of Ca2+ buffer
      proteins in excitable cells.
AB  - BACKGROUND: Cytosolic Ca2+ buffers are members of the large family of Ca2+
      binding proteins and are essential components of the Ca2+ signaling toolkit
      implicated in the precise regulation of intracellular Ca2+ signals. Their
      physiological role in excitable cells has been investigated in vivo by analyzing
      the phenotype of mice either lacking one of the Ca2+ buffers or mice with ectopic
      expression. SCOPE OF REVIEW: In this review, results obtained with knockout mice
      for the three most prominent Ca2+ buffers, parvalbumin, calbindin-D28k and
      calretinin are summarized. MAJOR CONCLUSIONS: The absence of Ca2+ buffers in
      specific neuron subpopulations, and for parvalbumin additionally in fast-twitch
      muscles, leads to Ca2+ buffer-specific changes in intracellular Ca2+ signals.
      This affects the excitation-contraction cycle in parvalbumin-deficient muscles,
      and in Ca2+ buffer-deficient neurons, properties associated with synaptic
      transmission (e.g. short-term modulation), excitability and network oscillations
      are altered. These findings have not only resulted in a better understanding of
      the physiological function of Ca2+ buffers, but have revealed that the absence of
      Ca2+ signaling toolkit components leads to protein-and neuron-specific
      adaptive/homeostatic changes that also include changes in neuron morphology (e.g.
      altered spine morphology, changes in mitochondria content) and network
      properties. GENERAL SIGNIFICANCE: The complex phenotype of Ca2+ buffer knockout
      mice arises from the direct effect of these proteins on Ca2+ signaling and
      moreover from the homeostatic mechanisms induced in these mice. For a better
      mechanistic understanding of neurological diseases linked to disturbed/altered
      Ca2+ signaling, a global view on Ca2+ signaling is expected to lead to new
      avenues for specific therapies. This article is part of a Special Issue entitled
      Biochemical, biophysical and genetic approaches to intracellular calcium
      signaling.

PMID- 22138449
TI  - Microphthalmia-associated transcription factor is required for mature myotube
      formation.
AB  - BACKGROUND: The roles of microphthalmia-associated transcription factor (Mitf) in
      the skeletal muscle and during myogenesis are unclear. METHODS: Expression of
      Mitf in mouse tissues and during myogenesis was evaluated. Effects of Mitf
      knockdown on myogenesis and gene expression related to myogenesis were
      subsequently explored. Furthermore, effects of p21, a cyclin-dependent kinase
      inhibitor, and integrin alpha9 (Itga9) were examined. RESULTS: Mitf was highly
      expressed in the skeletal muscle; Mitf-A and -J were expressed. Mitf expression
      increased after differentiation stimulation in C2C12 myogenic cells. Down
      regulation of Mitf expression by transfection of siRNA for common Mitf inhibited
      myotube formation, which was reproduced by Mitf-A knockdown. Morphometric
      analyses indicated that both multinucleated cell number and the proportion of
      myotubes with more than 6 nuclei were decreased in Mitf-knockdown cells,
      suggesting that Mitf is required for not only the formation of nascent myotubes
      but also their maturation. Searching for genes positively regulated by Mitf
      revealed p21 and Itga9; decreasing Mitf expression inhibited up-regulation of p21
      expression after differentiation stimulation and blocked the induction of Itga9
      expression in response to differentiation. Knockdown of p21 decreased the number
      of multinucleated cells, whereas Itga9 knockdown did not affect the myotube
      number. Both p21 knockdown and Itga9 knockdown decreased the proportion of
      myotubes with more than 6 nuclei. GENERAL SIGNIFICANCE: Mitf positively regulates
      skeletal muscle formation; Mitf is significantly expressed during myogenesis, and
      is required for efficient myotube formation through expression of p21 and Itga9.

PMID- 22138450
TI  - Extraction, purification and antibacterial activities of a polysaccharide from
      spent mushroom substrate.
AB  - To contribute towards effective exploitation and utilization of spent mushroom
      substrate (SMS), a water-soluble polysaccharide named PL was isolated and
      purified from SMS. The total sugar content and monosaccharide composition were
      analyzed by phenol-sulfuric acid method and capillary electrophoresis, and
      infrared spectroscopy was also performed for structure characterization. The
      results showed that the total sugar content of crude polysaccharide from SMS was
      about 25.8%, the polysaccharide contained two fractions (PL1 and PL2), which was
      mainly composed of glucose, rhamnose and mannose with a molar ratio of
      1:3.13:1.16. The attributions of the main absorptions of both PL1 and PL2 were
      characteristic of glycosidic structures, and the FT-IR spectra of PL2 and
      lentinan were very similar. Escherichia coli, Staphylococcus aureus and Sarcina
      lutea were used to study the antibacterial activity and minimal inhibitory
      concentrations (MICs) of the polysaccharide. The antibacterial activity of
      polysaccharide from SMS against E. coli was the strongest, while the weakest
      against S. lutea, and the MICs of PL2 were 12.5, 25 and 100 MUg/mL, respectively.

PMID- 22138451
TI  - Carboxymethyl tamarind kernel polysaccharide nanoparticles for ophthalmic drug
      delivery.
AB  - Tropicamide-loaded carboxymethyl tamarind kernel polysaccharide (CMTKP)
      nanoparticles were prepared and evaluated for ocular delivery. Preparation of
      ionotropically gelled CMTKP nanoparticles was optimized employing three-levels,
      two-factor central composite design. Concentration of polymer and crosslinker had
      significant synergistic effect on particle size and % encapsulation efficiency.
      The optimal calculated parameters were concentrations of CMTKP 0.10% (w/v) and
      calcium chloride 0.11% (w/v). The optimized tropicamide-loaded CMTKP formulation
      showed ex vivo corneal permeation of tropicamide across isolated goat cornea
      comparable to its aqueous solution. Further, the mucoadhesive and non-irritant
      nature of CMTKP nanoparticles indicate their suitability as ocular delivery
      system.

PMID- 22138452
TI  - A meta-analysis of experimental studies of diversion programs for juvenile
      offenders.
AB  - OBJECTIVE: Research to establish an evidence-base for the treatment of conduct
      problems and delinquency in adolescence is well established; however, an evidence
      base for interventions with offenders who are diverted from the juvenile justice
      system has yet to be synthesized. The purpose of this study was to conduct a meta
      analysis of experimental studies testing juvenile diversion programs and to
      examine the moderating effect of program type and implementation quality. METHOD:
      A literature search using PsycINFO, Web of Science, and the National Criminal
      Justice Reference Service data-bases and research institute websites yielded 28
      eligible studies involving 57 experimental comparisons and 19,301 youths.
      RESULTS: Recidivism was the most common outcome reported across all studies.
      Overall, the effect of diversion programs on recidivism was non-significant
      (k=45, OR=0.83, 95%CI=0.43-1.58). Of the five program types identified, including
      case management (k=18, OR=0.78), individual treatment (k=11, OR=0.83), family
      treatment (k=4, OR=0.57), youth court (k=6, OR=0.93), and restorative justice
      (k=6, OR=0.87), only family treatment led to a statistically significant
      reduction in recidivism. Restorative justice studies that were implemented with
      active involvement of researchers led to statistically significant reductions in
      recidivism (k=3, OR=0.69). Other outcomes, including frequency of offending,
      truancy, and psycho-social problems were reported infrequently and were not
      subjected to meta-analysis. CONCLUSIONS: High levels of heterogeneity
      characterize diversion research. Results of this study recommend against
      implementation of programs limited to case management and highlight the promise
      of family interventions and restorative justice.

PMID- 22138453
TI  - The Written Declaration on Epilepsy: an important achievement for Europe and
      beyond.

PMID- 22138454
TI  - Treatment of displaced neck fractures of the femur with total hip arthroplasty.
AB  - We report our experience in unstable fractures of the femoral neck in a
      consecutive series of patients who underwent total hip arthroplasty. Over a
      period of 12 years, 88 patients were treated with a cemented total hip
      arthroplasty; 3 patients were lost to follow-up, leaving 86 fractures (85
      patients) for retrospective analysis. Seven patients had dislocations, all but 1
      of which were treated successfully without reoperation. Four patients required
      reoperation in the same hip undergoing arthroplasty. There was a graded increase
      in mortality rates across the continuum of risk groups at the time of surgery.
      The low incidence (4.6%) of a second procedure on the hip repaired initially, as
      well as low mortality rates, makes this treatment strategy quite satisfactory.

PMID- 22138456
TI  - Implementation of high-dose-rate brachytherapy and androgen deprivation in
      patients with prostate cancer.
AB  - PURPOSE: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer
      specific survival [CSS], disease-free survival [DFS], biochemical failure-free
      survival [BFS]), complications and morbidity in patients treated with high-dose
      rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims.
      METHODS: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were
      included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen
      (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20
      received multimodal treatment with conformal four-field radiotherapy
      (prostate/vesiculae 2 Gy * 25) combined with HDR-BT (iridium 192; prostate 10 Gy
      * 2) with long-term androgen deprivation therapy (ADT). RESULTS: After a median
      observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had
      relapsed clinically and/or biochemically and 10 patients were dead, of which 2
      patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS
      rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients
      with either Gleason score <8 or with intermediate risk profile had relapsed. The
      number of HDR-BT treatments was not related to outcome. Despite of age (median,
      65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39
      of 275 patients, Genitourinary treatment-related morbidity was moderate with long
      lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients
      (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2
      for gastrointestinal at follow-up. Complications during implantations were
      related to pubic arch interference (4 patients) and lithotomy time, causing 2
      patients to develop compartment syndrome. CONCLUSION: Despite still preliminary
      observations, our 5-year outcome estimates favor the implementation of high-dose
      rate brachytherapy in high-risk patients combined with conformal external
      radiotherapy and long-term ADT. High-quality implants can be achieved by a
      trained specialized team at a high-turnover center using transrectal ultrasound
      based treatment plans with acceptable morbidity and complication rates.

PMID- 22138455
TI  - Intranuclear delivery of a novel antibody-derived radiosensitizer targeting the
      DNA-dependent protein kinase catalytic subunit.
AB  - PURPOSE: To inhibit DNA double-strand break repair in tumor cells by delivery of
      a single-chain antibody variable region fragment (ScFv 18-2) to the cell nucleus.
      ScFv 18-2 binds to a regulatory region of the DNA-dependent protein kinase (DNA
      PK), an essential enzyme in the nonhomologous end-joining pathway, and inhibits
      DNA end-joining in a cell-free system and when microinjected into single cells.
      Development as a radiosensitizer has been limited by the lack of a method for
      intranuclear delivery to target cells. We investigated a delivery method based on
      folate receptor-mediated endocytosis. METHODS AND MATERIALS: A recombinant ScFv
      18-2 derivative was conjugated to folate via a scissile disulfide linker. Folate
      ScFv 18-2 was characterized for its ability to be internalized by tumor cells and
      to influence the behavior of ionizing radiation-induced repair foci.
      Radiosensitization was measured in a clonogenic survival assay. Survival curves
      were fitted to a linear-quadratic model, and between-group differences were
      evaluated by an F test. Sensitization ratios were determined based on mean
      inhibitory dose. RESULTS: Human KB and NCI-H292 lung cancer cells treated with
      folate-conjugated ScFv 18-2 showed significant radiosensitization (p < 0.001).
      Sensitization enhancement ratios were 1.92 +/- 0.42 for KB cells and 1.63 +/-
      0.13 for NCI-H292 cells. Studies suggest that treatment inhibits repair of
      radiation-induced DSBs, as evidenced by the persistence of gamma-H2AX-stained
      foci and by inhibition of staining with anti-DNA-PKcs phosphoserine 2056.
      CONCLUSIONS: Folate-mediated endocytosis is an effective method for intranuclear
      delivery of an antibody-derived DNA repair inhibitor.

PMID- 22138457
TI  - Spot scanning-based proton therapy for intracranial meningioma: long-term results
      from the Paul Scherrer Institute.
AB  - BACKGROUND: To assess the long-term clinical results of spot scanning proton
      therapy (PT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS:
      Thirty-nine patients with meningioma (histologically proven 34/39) were treated
      with PT between July 1997 and January 2010. Thirty-two (82.1%) patients were
      treated as primary treatment (exclusive PT, n = 8; postoperative PT, n = 24).
      Mean age was 48.3 +/- 17.9 years and 32 (82.1%) patients had skull base lesions.
      For patients undergoing surgery, 24 patients had a diagnosis of World Health
      Organization (WHO) Grade I and 10 of a WHO Grade II/III meningioma, respectively.
      The female-to-male ratio was 3.3. The median administered dose was 56.0 Gy
      (relative biologic effectiveness [RBE]) (range, 52.2-66.6) at 1.8-2.0 Gy (RBE)
      per fraction. Gross tumor volume (GTV) ranged from 0.76 to 546.5 cm(3) (median,
      21.5). Late toxicity was assessed according to Common Terminology Criteria for
      Adverse Events version 3.0. Mean follow-up time was 62.0 months and all patients
      were followed for >6 months. RESULTS: Six patients presented with tumor
      recurrence and 6 patients died during follow-up, of which 4 of tumor progression.
      Five-year actuarial local control and overall survival rates were 84.8% and
      81.8%, respectively, for the entire cohort and 100% for benign histology.
      Cumulative 5-year Grade >=3 late toxicity-free survival was 84.5%. On univariate
      analysis, LC was negatively influenced by WHO grade (p = 0.001), GTV (p = 0.013),
      and male gender (p = 0.058). CONCLUSIONS: PT is a safe and effective treatment
      for patients with untreated, recurrent, or incompletely resected intracranial
      meningiomas. WHO grade and tumor volume was an adverse prognostic factor for
      local control.

PMID- 22138458
TI  - Image-based 3D treatment planning for vaginal cylinder brachytherapy: dosimetric
      effects of bladder filling on organs at risk.
AB  - PURPOSE: To investigate the dosimetric effects of bladder filling on organs at
      risk (OARs) using three-dimensional image-based treatment planning for vaginal
      cylinder brachytherapy. METHODS AND MATERIALS: Twelve patients with endometrial
      or cervical cancer underwent postoperative high-dose rate vaginal cylinder
      brachytherapy. For three-dimensional planning, patients were simulated by
      computed tomography with an indwelling catheter in place (empty bladder) and with
      180 mL of sterile water instilled into the bladder (full bladder). The bladder,
      rectum, sigmoid, and small bowel (OARs) were contoured, and a prescription dose
      was generated for 10 to 35 Gy in 2 to 5 fractions at the surface or at 5 mm
      depth. For each OAR, the volume dose was defined by use of two different
      criteria: the minimum dose value in a 2.0-cc volume receiving the highest dose
      (D(2cc)) and the dose received by 50% of the OAR volume (D(50%)). International
      Commission on Radiation Units & Measurements (ICRU) bladder and rectum point
      doses were calculated for comparison. The cylinder-to-bowel distance was measured
      using the shortest distance from the cylinder apex to the contoured sigmoid or
      small bowel. Statistical analyses were performed with paired t tests. RESULTS:
      Mean bladder and rectum D(2cc) values were lower than their respective ICRU
      doses. However, differences between D(2cc) and ICRU doses were small. Empty vs.
      full bladder did not significantly affect the mean cylinder-to-bowel distance
      (0.72 vs. 0.92 cm, p = 0.08). In contrast, bladder distention had appreciable
      effects on bladder and small bowel volume dosimetry. With a full bladder, the
      mean small bowel D(2cc) significantly decreased from 677 to 408 cGy (p = 0.004);
      the mean bladder D(2cc) did not increase significantly (1,179 cGy vs. 1,246 cGy,
      p = 0.11). Bladder distention decreased the mean D(50%) for both the bladder (441
      vs. 279 cGy, p = 0.001) and the small bowel (168 vs. 132 cGy, p = 0.001). Rectum
      and sigmoid volume doses were not affected by bladder filling. CONCLUSIONS: In
      high-dose rate vaginal cylinder brachytherapy, treatment with a distended bladder
      preferentially reduces high dose to the small bowel around the vaginal cuff
      without a significant change in dose to the bladder, rectum, or sigmoid.

PMID- 22138459
TI  - Adaptive radiotherapy for head-and-neck cancer: initial clinical outcomes from a
      prospective trial.
AB  - PURPOSE: To present pilot toxicity and survival outcomes for a prospective trial
      investigating adaptive radiotherapy (ART) for oropharyngeal squamous cell
      carcinoma. METHODS AND MATERIALS: A total of 24 patients were enrolled in an
      institutional review board-approved clinical trial; data for 22 of these patients
      were analyzed. Daily CT-guided setup and deformable image registration permitted
      serial mapping of clinical target volumes and avoidance structures for ART
      planning. Primary site was base of tongue in 15 patients, tonsil in 6 patient,
      and glossopharyngeal sulcus in 1 patient. Twenty patients (91%) had American
      Joint Committee on Cancer (AJCC) Stage IV disease. T stage distribution was 2 T1,
      12 T2, 3 T3, 5 T4. N stage distribution was 1 N0, 2 N1, 5 N2a, 12 N2b, and 2 N2c.
      Of the patients, 21 (95%) received systemic therapy. RESULTS: With a 31-month
      median follow-up (range, 13-45 months), there has been no primary site failure
      and 1 nodal relapse, yielding 100% local and 95% regional disease control at 2
      years. Baseline tumor size correlated with absolute volumetric treatment response
      (p = 0.018). Parotid volumetric change correlated with duration of feeding tube
      placement (p = 0.025). Acute toxicity was comparable to that observed with
      conventional intensity-modulated radiotherapy (IMRT). Chronic toxicity and
      functional outcomes beyond 1 year were tabulated. CONCLUSION: This is the first
      prospective evaluation of morbidity and survival outcomes in patients with
      locally advanced head-and-neck cancer treated with automated adaptive replanning.
      ART can provide dosimetric benefit with only one or two mid-treatment replanning
      events. Our preliminary clinical outcomes document functional recovery and
      preservation of disease control at 1-year follow-up and beyond.

PMID- 22138460
TI  - Influence of lymphatic invasion on locoregional recurrence following mastectomy:
      indication for postmastectomy radiotherapy for breast cancer patients with one to
      three positive nodes.
AB  - PURPOSE: The indication for postmastectomy radiotherapy (PMRT) in breast cancer
      patients with one to three positive lymph nodes has been in discussion. The
      purpose of this study was to identify patient groups for whom PMRT may be
      indicated, focusing on varied locoregional recurrence rates depending on
      lymphatic invasion (ly) status. METHODS AND MATERIALS: Retrospective analysis of
      1,994 node-positive patients who had undergone mastectomy without postoperative
      radiotherapy between January 1990 and December 2000 at our hospital was
      performed. Patient groups for whom PMRT should be indicated were assessed using
      statistical tests based on the relationship between locoregional recurrence rate
      and ly status. RESULTS: Multivariate analysis showed that the ly status affected
      the locoregional recurrence rate to as great a degree as the number of positive
      lymph nodes (p < 0.001). Especially for patients with one to three positive
      nodes, extensive ly was a more significant factor than stage T3 in the TNM
      staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). CONCLUSION:
      Among postmastectomy patients with one to three positive lymph nodes, patients
      with extensive ly seem to require local therapy regimens similar to those used
      for patients with four or more positive nodes and also seem to require
      consideration of the use of PMRT.

PMID- 22138461
TI  - Preradiotherapy calcium scores of the coronary arteries in a cohort of women with
      early-stage breast cancer: a comparison with a cohort of healthy women.
AB  - PURPOSE: Breast cancer radiotherapy has been associated with an increased risk of
      cardiac toxicity. However, no data are available on the probability of developing
      coronary artery disease (CAD) in breast cancer patients when compared with
      healthy women. Therefore, baseline coronary artery calcium (CAC) scores, as an
      accepted tool to predict CAD, were determined and compared with the CAC scores of
      a healthy, asymptomatic cohort, the Multi-Ethnic Study of Atherosclerosis (MESA)
      cohort. METHODS AND MATERIALS: Eighty consecutive patients with ductal carcinoma
      in situ or infiltrative breast cancer referred for radiotherapy after breast
      conserving surgery were included in our study. Their cardiovascular risk profile
      was registered, and a 64 multislice CT scan was performed. The CAC scores of an
      unselected (Caucasian only) Radiotherapy Centre West (RCWEST) cohort, as well as
      of those of a selected (comorbidity and race adjusted) RCWEST cohort, were
      determined. The scores of both cohorts were compared with those of the female
      (Caucasian only) MESA cohort. RESULTS: For the unselected RCWEST cohort (n = 62)
      we found significant (p < .01) higher scores for women in the 55-64 age category
      compared with those of the MESA cohort. In the selected cohort (n = 55) the CAC
      scores of the women in the age category 55-64 were significantly (p = .02) higher
      compared with the MESA cohort. No significant differences were noted in the other
      age categories. CONCLUSION: Both cohorts revealed that CAC scores in the 55-64
      age category were significantly higher than the CAC scores in the asymptomatic
      (female) MESA population. These data suggest that breast cancer patients bear a
      higher risk of developing coronary heart disease before the start of
      radiotherapy. Therefore, measures to decrease cardiac dose further in breast
      cancer radiotherapy are even more important.

PMID- 22138462
TI  - Low-dose-rate californium-252 neutron intracavitary afterloading radiotherapy
      combined with conformal radiotherapy for treatment of cervical cancer.
AB  - PURPOSE: To study the efficacy of low-dose-rate californium-252 ((252)Cf) neutron
      intracavitary afterloading radiotherapy (RT) combined with external pelvic RT for
      treatment of cervical cancer. METHODS AND MATERIALS: The records of 96 patients
      treated for cervical cancer from 2006 to 2010 were retrospectively reviewed. For
      patients with tumors <=4 cm in diameter, external beam radiation was performed
      (1.8 Gy/day, five times/week) until the dose reached 20 Gy, and then (252)Cf
      neutron intracavitary afterloading RT (once/week) was begun, and the frequency of
      external beam radiation was changed to four times/week. For patients with tumors
      >4 cm, (252)Cf RT was performed one to two times before whole-pelvis external
      beam radiation. The tumor-eliminating dose was determined by using the depth
      limit of 5 mm below the mucosa as the reference point. In all patients, the total
      dose of the external beam radiation ranged from 46.8 to 50 Gy. For (252)Cf RT,
      the dose delivered to point A was 6 Gy/fraction, once per week, for a total of
      seven times, and the total dose was 42 Gy. RESULTS: The mean +/- SD patient age
      was 54.7 +/- 13.7 years. Six patients had disease assessed at stage IB, 13
      patients had stage IIA, 49 patients had stage IIB, 3 patients had stage IIIA, 24
      patients had stage IIIB, and 1 patient had stage IVA. All patients obtained
      complete tumor regression (CR). The mean +/- SD time to CR was 23.5 +/- 3.4 days.
      Vaginal bleeding was fully controlled in 80 patients within 1 to 8 days. The mean
      +/- SD follow-up period was 27.6 +/- 12.7 months (range, 6-48 months). Five
      patients died due to recurrence or metastasis. The 3-year survival and disease
      free recurrence rates were 89.6% and 87.5 %, respectively. Nine patients
      experienced mild radiation proctitis, and 4 patients developed radiocystitis.
      CONCLUSIONS: Low-dose-rate (252)Cf neutron RT combined with external pelvic RT is
      effective for treating cervical cancer, with a low incidence of complications.

PMID- 22138463
TI  - Proton radiotherapy for high-risk pediatric neuroblastoma: early outcomes and
      dose comparison.
AB  - PURPOSE: To report the early outcomes for children with high-risk neuroblastoma
      treated with proton radiotherapy (RT) and to compare the dose distributions for
      intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D
      CPT), and intensity-modulated proton RT to the postoperative tumor bed. METHODS
      AND MATERIALS: All patients with high-risk (International Neuroblastoma Staging
      System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our
      institution were included. All patients received induction chemotherapy, surgical
      resection of residual disease, high-dose chemotherapy with stem cell rescue, and
      adjuvant 3D-CPT to the primary tumor sites. The patients were followed with
      clinical examinations, imaging, and laboratory testing every 6 months to monitor
      disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT
      plans were generated and compared for a representative case of adjuvant RT to the
      primary tumor bed followed by a boost. RESULTS: Nine patients were treated with
      3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and
      all patients had Stage IV disease. All patients had unfavorable histologic
      characteristics (poorly differentiated histologic features in 8, N-Myc
      amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor
      size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median
      follow-up of 38 months (range 11-70), there were no local failures. Four patients
      developed distant failure, and, of these, two died of disease. Acute side effects
      included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients.
      Although comparable target coverage was achieved with all three modalities,
      proton therapy achieved substantial normal tissue sparing compared with IMRT.
      Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs,
      and heart. CONCLUSIONS: Preliminary outcomes reveal excellent local control with
      proton therapy for high-risk neuroblastoma, although distant failures continu to
      occur. Dosimetric comparisons demonstrate the advantage of proton RT compared
      with IMRT in this setting, allowing more conformal treatment and better normal
      tissue sparing.

PMID- 22138464
TI  - A MALDI-TOF MS method for the simultaneous and quantitative analysis of neutral
      and sialylated glycans of CHO-expressed glycoproteins.
AB  - The development of a MALDI-TOF MS method for the quantitative analysis of the
      glycosylation of CHO-expressed biotherapeutic glycoproteins shall be presented.
      The method utilizes a well-established chemistry, reductive amination of glycans,
      to derivatize glycans with either a light analog ((12)C(7) anthranilic acid) or a
      heavy analog ((13)C(7) anthranilic acid) to allow for the direct comparison of
      the alternately-labeled glycans by MALDI-TOF MS. The method allows for the
      simultaneous analysis of neutral and sialylated glycans and displays a linear
      dynamic range over two orders of magnitude with sub-picomolar sensitivity.
      Additionally, because the glycans are derivatized with anthranilic acid, which is
      a very sensitive fluorophore, the glycans can be analyzed by chromatography with
      fluorescence detection. The need for this type of method is highlighted by the
      biotechnology/biopharmaceutical industry's continuous drive towards fully
      understanding process control. By providing this type of quantitative data,
      glycosylation changes of the expressed protein can be easily observed thereby
      helping to further advance the understanding of a major aspect of the
      biopharmaceutical process.

PMID- 22138465
TI  - Label-free virus detection using silicon photonic microring resonators.
AB  - Viruses represent a continual threat to humans through a number of mechanisms,
      which include disease, bioterrorism, and destruction of both plant and animal
      food resources. Many contemporary techniques used for the detection of viruses
      and viral infections suffer from limitations such as the need for extensive
      sample preparation or the lengthy window between infection and measurable immune
      response, for serological methods. In order to develop a method that is fast,
      cost-effective, and features reduced sample preparation compared to many other
      virus detection methods, we report the application of silicon photonic microring
      resonators for the direct, label-free detection of intact viruses in both
      purified samples as well as in a complex, real-world analytical matrix. As a
      model system, we demonstrate the quantitative detection of Bean pod mottle virus,
      a pathogen of great agricultural importance, with a limit of detection of 10
      ng/mL. By simply grinding a small amount of leaf sample in buffer with a mortar
      and pestle, infected leaves can be identified over a healthy control with a total
      analysis time of less than 45 min. Given the inherent scalability and
      multiplexing capability of the semiconductor-based technology, we feel that
      silicon photonic microring resonators are well-positioned as a promising
      analytical tool for a number of viral detection applications.

PMID- 22138466
TI  - Designing bifunctionalized gold nanoparticle for colorimetric detection of Pb2+
      under physiological condition.
AB  - In the present work, a kind of peptide functionalized gold nanoparticle (AuNP)
      has been synthesized and employed for colorimetric detection of Pb(2+) in both
      aqueous solution and living cell. The AuNPs are capped by two peptide ligands:
      glutathione (GSH) and pentapeptide (CALNN). The GSH is used as a functional group
      for selectively sensing Pb(2+) by coordination reaction, and CALNN is employed as
      a stabilize ligand for improving the stability of AuNPs under physiological
      condition, respectively. The AuNP enables to strongly interact with Pb(2+) that
      leads to distinct color change of solution. Under the optimized molar ratio of
      GSH to CALNN on the AuNP surface, the colorimetric assay for detecting Pb(2+) in
      living cell downs to 2.9 fmol Pb(2+)per cell (3 times of standard deviation,
      3sigma) with linear relationship from 2.9 to 37.7 fmol Pb(2+) per cell. In
      addition, the method also shows highly selective detection toward Pb(2+) against
      other common metal ions in both aqueous solution and living cell.

PMID- 22138467
TI  - Development of a label-free and innovative approach based on surface plasmon
      resonance biosensor for on-site detection of infectious bursal disease virus
      (IBDV).
AB  - An innovative, specific and label-free detection approach based on optical
      surface plasmon resonance (SPR) was developed and employed in the development of
      a rapid and quantitative bioanalyzer for detecting infectious bursal disease
      virus (IBDV) in the field. A unique bioanalyzer based on this approach was
      established which consists of a micro-flow cell, a temperature regulator, an
      integrated biosensor, an optical platform, an electronic control unit
      incorporated into a photoelectric conversion device, and a universal serial bus
      (USB) interface circuit board. The procedure for detecting IBDV was
      systematically described, and experimentally validated. The self-assembly
      technology was used to make the IBDmAb adhere to the surface of the sensor chip
      by a bifunctional cross-linker. By this approach there exhibited a linear
      relationship between the IBDV concentrations and the corresponding responses in
      the range of dilution factors from 100 to 1600 with R(2) 0.97982. We were able to
      detect 400-fold diluted IBDV using this biochip repeatedly with a calculated
      relative standard deviation (RSD) of 3.6%. We also showed that the detection
      limit of the SPR biosensor biochip was around 1/18 of the detection limit of the
      IBDV diagnostic strip. Satisfactory recoveries were obtained from the recovery
      test. The approach presented here was shown to have great potential to be used in
      the IBDV epidemic regions and hence help to promote the effective implementation
      of sound control strategies against IBDV.

PMID- 22138468
TI  - Modification of standard CMOS technology for cell-based biosensors.
AB  - We present an electrode based on complementary metal oxide semiconductor (CMOS)
      technology that can be made fully biocompatible and chemically inert using a
      simple, low-cost and non-specialised process. Since these devices are based on
      ubiquitous CMOS technology, the integrated circuits can be readily developed to
      include appropriate amplifiers, filters and wireless subsystems, thus reducing
      the complexity and cost of external systems. The unprocessed CMOS aluminium
      electrodes are modified using anodisation and plating techniques which do not
      require intricate and expensive semiconductor processing equipment and can be
      performed on the bench-top as a clean-room environment is not required. The
      resulting transducers are able to detect both the fast electrical activity of
      neurons and the slow changes in impedance of growing and dividing cells. By using
      standard semiconductor fabrication techniques and well-established technologies,
      the approach can form the basis of cell-based biosensors and transducers for high
      throughput drug discovery assays, neuroprosthetics and as a basic research tool
      in biosciences. The technology is equally applicable to other biosensors that
      require noble metal or nanoporous microelectrodes.

PMID- 22138469
TI  - A protein-based biointerfacing route toward label-free immunoassays with long
      period gratings in transition mode.
AB  - We present a fast and effective method for anchoring bioreceptors to optical
      waveguides exhibiting a poorly reactive polymer interface and that have to be
      minimally perturbed with respect to their design. The study originated from the
      need to biofunctionalize a fiber optic Long Period Grating (LPG) that is tuned in
      a highly sensitive working point, the so-called transition mode, through the
      deposition of a high refractive index overlay. In particular, a thin film of
      atactic polystyrene (PS) was dip-coated onto the LPG with a thickness suitable to
      optimize the LPG sensitivity to refractive index changes of the surrounding
      medium. Bovine serum albumin was selected as sacrificial layer for its well-known
      adhesion capabilities to PS surfaces, then glutaraldehyde was used to conjugate
      IgGs, serving as prototypical bioreceptor, on the device surface. The
      effectiveness of the immobilization method was assessed by studying the
      interaction between the immobilized IgG with a suitable anti-IgG. In a
      preliminary study performed by means of ELISA and surface plasmon resonance,
      optimal conditions for the biomolecular testing with the LPG were assessed. Four
      distinct interactions were thus monitored in real time following the shift of the
      LPG attenuation band. These experiments suggest a novel and interesting
      biofunctionalization approach of unreactive polymers with applications in
      immunosensing and basic life science research.

PMID- 22138470
TI  - A novel oxyconforming response in the freshwater fish Galaxias maculatus.
AB  - How fish oxygen consumption is modulated by external PO(2) has long been a matter
      of interest, yet is an experimentally complicated question to answer. In this
      study closed and semi-closed respirometry were used to evaluate the oxygen
      consumption rate of the scaleless galaxiid fish, inanga (Galaxias maculatus) as a
      function of decreasing external PO(2). Both respirometry techniques showed that
      as environmental oxygen levels declined, oxygen consumption rates also decreased.
      At no point did inanga regulate oxygen consumption. This is strong evidence that
      inanga is an oxyconformer. Partitioned respirometry experiments showed that skin
      plays an important role in oxygen uptake in this fish species, and cutaneous
      oxygen uptake may have an important role in shaping the oxygen consumption
      response to hypoxia.

PMID- 22138472
TI  - BIN1 is reduced and Cav1.2 trafficking is impaired in human failing
      cardiomyocytes.
AB  - BACKGROUND: Heart failure is a growing epidemic, and a typical aspect of heart
      failure pathophysiology is altered calcium transients. Normal cardiac calcium
      transients are initiated by Cav1.2 channels at cardiac T tubules. Bridging
      integrator 1 (BIN1) is a membrane scaffolding protein that causes Cav1.2 to
      traffic to T tubules in healthy hearts. The mechanisms of Cav1.2 trafficking in
      heart failure are not known. OBJECTIVE: To study BIN1 expression and its effect
      on Cav1.2 trafficking in failing hearts. METHODS: Intact myocardium and freshly
      isolated cardiomyocytes from nonfailing and end-stage failing human hearts were
      used to study BIN1 expression and Cav1.2 localization. To confirm Cav1.2 surface
      expression dependence on BIN1, patch-clamp recordings were performed of Cav1.2
      current in cell lines with and without trafficking-competent BIN1. Also, in adult
      mouse cardiomyocytes, surface Cav1.2 and calcium transients were studied after
      small hairpin RNA-mediated knockdown of BIN1. For a functional readout in intact
      heart, calcium transients and cardiac contractility were analyzed in a zebrafish
      model with morpholino-mediated knockdown of BIN1. RESULTS: BIN1 expression is
      significantly decreased in failing cardiomyocytes at both mRNA (30% down) and
      protein (36% down) levels. Peripheral Cav1.2 is reduced to 42% by imaging, and a
      biochemical T-tubule fraction of Cav1.2 is reduced to 68%. The total calcium
      current is reduced to 41% in a cell line expressing a nontrafficking BIN1 mutant.
      In mouse cardiomyocytes, BIN1 knockdown decreases surface Cav1.2 and impairs
      calcium transients. In zebrafish hearts, BIN1 knockdown causes a 75% reduction in
      calcium transients and severe ventricular contractile dysfunction. CONCLUSIONS:
      The data indicate that BIN1 is significantly reduced in human heart failure, and
      this reduction impairs Cav1.2 trafficking, calcium transients, and contractility.

PMID- 22138473
TI  - Length-dependent compaction of intrinsically disordered proteins.
AB  - This work investigates the effect of chain length on the degree of compaction of
      intrinsically disordered proteins (IDPs). The three main IDP types, native coil
      (NC), pre-molten globule (PMG) and molten globule (MG), are compared by means of
      a compaction index (CI) normalized for chain length. The results point out a
      strong variability of compactness as a function of chain length within each
      group, with larger proteins populating more compact states. While qualitative
      sequence features are responsible for the main differences among groups, chain
      length seems to have an unspecific effect modulating the extent of compaction
      within each group. The results are consistent with a cooperative character of the
      weak interactions responsible for chain collapse.

PMID- 22138474
TI  - Upgrading cytochrome P450 activity in HepG2 cells co-transfected with adenoviral
      vectors for drug hepatotoxicity assessment.
AB  - In a number of adverse drug reactions leading to hepatotoxicity, drug metabolism
      is thought to be involved by the generation of reactive metabolites from non
      toxic drugs. The use of hepatoma cell lines, such as HepG2 cell line, for the
      evaluation of drug-induced hepatotoxicity is hampered by their low cytochrome
      P450 expression which makes impossible the study of the toxicity produced by
      bioactivable compounds. Genetically manipulated cells constitute promising tools
      for hepatotoxicity applications. HepG2 cells were simultaneously transfected with
      recombinant adenoviruses encoding CYP1A2, CYP2C9 and CYP3A4 to confer them drug
      metabolic competence. Upgraded cells (Adv-HepG2) were highly able to metabolize
      the toxin studied in contrast to the reduced metabolic capacity of HepG2 cells.
      Aflatoxin B1-induced hepatotoxicity was studied as a proof of concept in
      metabolically competent and non-competent HepG2 cells by using high content
      screening technology. Significant differences in mitochondrial membrane
      potential, intracellular calcium concentration, nuclear morphology and cell
      viability after treatment with aflatoxin B1 were observed in Adv-HepG2 when
      compared to HepG2 cells. Rotenone (non bioactivable) and citrate (non
      hepatotoxic) were analysed as negative controls. This cell model showed to be a
      suitable hepatic model to test hepatotoxicity of bioactivable drugs and
      constitutes a valuable alternative for hepatotoxicity testing.

PMID- 22138475
TI  - Nerolidol effects on mitochondrial and cellular energetics.
AB  - In the present work, we evaluated the potential toxic effects of nerolidol, a
      sesquiterpenoid common in plants essential oils, both on mitochondrial and
      cellular energetics. Samples of enriched natural extracts of nerolidol (a racemic
      mixture of cis and trans isomers) were tested on rat liver mitochondria and a
      decrease in phosphorylative system was observed but not in the mitochondrial
      respiratory chain activity, which reflects a direct effect on F1-ATPase. Hence,
      respiratory control ratio was also decreased. Cellular ATP/ADP levels were
      significantly decreased in a concentration-dependent manner, possibly due to the
      direct effect of nerolidol on F(0)F(1)-ATPsynthase. Nerolidol stimulates
      respiratory activity probably due to an unspecific effect, since it does not show
      any protonophoric effect. Furthermore, we observed that mitochondrial
      permeability transition was delayed in the presence of nerolidol, possibly due to
      its antioxidant activity and because this compound decreases mitochondrial
      transmembrane electric potential. Our results also show that, in human
      hepatocellular liver carcinoma cell line (HepG2), nerolidol both induces cell
      death and arrests cell growth, probably related with the observed lower
      bioenergetic efficiency.

PMID- 22138477
TI  - Variability in COPD: the PLATINO study viewpoint.

PMID- 22138476
TI  - Chronic thromboembolic pulmonary hypertension due to upper-extremity deep vein
      thrombosis caused by thoracic outlet syndrome.
AB  - We report on a 20 year-old woman diagnosed with pulmonary embolism (PE) and right
      subclavian vein thrombosis attributable to stasis caused by right clavicular
      prominence. At the 10-months follow-up, the patient had developed chronic
      thromboembolic pulmonary hypertension (CTEPH), and treatment was begun with a
      dual endothelin receptor antagonist. Very few cases of deep venous thrombosis of
      upper limb have been reported in relation to anatomical abnormalities. This case
      is also exceptional because the patient developed a chronic thromboembolic
      pulmonary hypertension, whose incidence is estimated at 0.5% of all symptomatic
      PE.

PMID- 22138479
TI  - Novel chromosomal translocation (17;22)(q12;q12) in a case of myelodisplastic
      syndrome characterized with signs of hemolytic anemia at presentation.
AB  - Myelodysplastic syndromes (MDS) are clonal stem cell diseases that can result in
      cytopenias, dysplasia in one or more cell lineages, infective hematopoiesis, and
      increase the risk of progression to acute myeloid leukemia (AML). MDSs are
      characterized by several recurrent cytogenetic defects, which can affect
      diagnosis, prognosis, and treatment. Some of that chromosomal alterations are
      associated with very poor prognosis. Conventional cytogenetics cannot accurately
      define the rearranged karyotype. Instead, molecular cytogenetics analyses can
      provide important diagnostic and prognostic information for patients affected by
      MDS, allowing the characterization of the whole mutational spectrum and, mainly,
      novel chromosomal lesions. In this paper, we report a MDS case with a novel
      chromosomal translocation [t(17;22)(q12;q22)], described for the first time here.
      Following Giemsa-banding karyotyping, fluorescent in situ hybridization analyses,
      by using chromosome-specific probes, displayed the breakpoint regions at
      chromosomes 17 and 22, within which intra and inter-chromosomal segmental
      duplications (SD) are present. Because of the occurrence of SDs in breakpoint
      region, it was not possible to finely define the genomic regions where breaks
      fell. Further investigations could be required to better understand the molecular
      basis of the novel translocation t(17;22)(q12;q12) acting in MDS context and to
      explain if SDs could contribute to the pathogenesis of MDS.

PMID- 22138480
TI  - Comparative transcriptomics and gene expression in larval tiger salamander
      (Ambystoma tigrinum) gill and lung tissues as revealed by pyrosequencing.
AB  - Biologists are beginning to unravel the complexities of gene expression in model
      organisms by studying the transcriptome, the complement of genes that are
      transcribed in a given tissue. It is unclear, however, if findings from model
      systems apply to non-model organisms because of environmental effects on gene
      expression. Furthermore, there have been few efforts to quantify how
      transcriptome or gene expression varies across individuals and across tissues in
      natural environments. Herein, we describe transcriptomic profiling of gene
      expression in lung and gill tissue of three larval tiger salamanders. We do so
      with a hierarchical experimental design that captures variation in expression
      among genes, among tissues, and among individuals. Using 454 pyrosequencing, we
      produced high-quality sequence data of 59 megabases and assembled ~200,000 reads
      into 19,501 contigs. These contigs BLASTed to 3,599 transcripts, of which 721
      were expressed in both tissues, 1,668 were unique to gill, and 1,210 unique to
      lung. Our data showed tissue-specific patterns in gene expression level with
      variation among transcripts and individuals. We identified genes and gene
      ontology terms related to respiration and compared their relative expression
      levels between gill and lung tissues. We also found evidence of exogenous genes
      associated with larval salamanders, and we identified ~1400 potential molecular
      markers (microsatellites and single nucleotide polymorphisms) that are associated
      with expressed genes. Given the tissue-specific differences we observed in
      transcriptomes, these data reinforce the idea that changes in gene expression
      serve as a primary mechanism underlying phenotypic plasticity.

PMID- 22138481
TI  - Sequencing and annotated analysis of an Estonian human genome.
AB  - In present study we describe the sequencing and annotated analysis of the
      individual genome of Estonian. Using SOLID technology we generated 2,449,441,916
      of 50-bp reads. The Bioscope version 1.3 was used for mapping and pairing of
      reads to the NCBI human genome reference (build 36, hg18). Bioscope enables also
      the annotation of the results of variant (tertiary) analysis. The average mapping
      of reads was 75.5% with total coverage of 107.72 Gb. resulting in mean fold
      coverage of 34.6. We found 3,482,975 SNPs out of which 352,492 were novel. 21,222
      SNPs were in coding region: 10,649 were synonymous SNPs, 10,360 were
      nonsynonymous missense SNPs, 155 were nonsynonymous nonsense SNPs and 58 were
      nonsynonymous frameshifts. We identified 219 CNVs with total base pair coverage
      of 37,326,300 bp and 87,451 large insertion/deletion polymorphisms covering
      10,152,256 bp of the genome. In addition, we found 285,864 small size
      insertion/deletion polymorphisms out of which 133,969 were novel. Finally, we
      identified 53 inversions, 19 overlapped genes and 2 overlapped exons.
      Interestingly, we found the region in chromosome 6 to be enriched with the coding
      SNPs and CNVs. This study confirms previous findings, that our genomes are more
      complex and variable as thought before. Therefore, sequencing of the personal
      genomes followed by annotation would improve the analysis of heritability of
      phenotypes and our understandings on the functions of genome.

PMID- 22138482
TI  - Cloning and characterization of a novel cellobiase gene, cba3, encoding the first
      known beta-glucosidase of glycoside hydrolase family 1 of Cellulomonas biazotea.
AB  - A novel cellobiase gene, designated cba3, was cloned from Cellulomonas biazotea.
      Although cellobiase genes of C. biazotea were previously cloned, published and/or
      patented, they encoded beta-glucosidases all belonging to glycoside hydrolase
      family 3 (GH3); the new Cba3 cellobiase was identified to be a glycoside
      hydrolase family 1 (GH1) member, which represents the first discovered GH1 beta
      glucosidase of C. biazotea. Escherichia coli transformants expressing recombinant
      Cba3 were shown to grow readily in minimal media using cellobiose as the sole
      carbon source, supporting the conclusion that Cba3 is a genuine cellobiase. The
      full-length cba3 gene was revealed by sequencing to be 1344 bp long. Cba3
      deletants lacking either the N-terminal 10 amino acids or the C-terminal 10
      residues were found to be biologically inactive, supporting the importance of
      both ends in catalysis. Like other GH1 beta-glucosidases, Cba3 was shown to
      contain the highly conserved NEP and ENG motifs, which are crucial for enzymatic
      activity. Despite lacking a classical N-terminal signal peptide, Cba3 was
      demonstrated to be a secretory protein. The findings that Cba3 is a cellobiase,
      and that it was expressed well as an extracellular protein in E. coli, support
      the potential of Cba3 for use with other cellulases in the hydrolysis of
      cellulosic biomass.

PMID- 22138483
TI  - E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with
      thymidine analog mutations.
AB  - BACKGROUND: HIV-1 accessory Vpr protein is involved in the reverse transcription
      process and has been shown to modulate the virus mutation rate. This process may
      play a role in the kinetics of appearance of drug resistance mutations under
      antiretroviral treatment. METHODS: Vpr sequences were analyzed from plasma
      viruses derived from 97 HIV-1-infected individuals failing antiretroviral
      treatment and 63 antiretroviral-naive patients. Vpr genetic variability was
      analyzed for association with specific drug treatment and drug resistance
      mutations. Biological and virological experiments were employed to characterize a
      mutation in Vpr found to be associated with virological failure. RESULTS: E17A
      mutation located in the first alpha-helix of Vpr was more prevalent in HAART
      treated individuals compared to untreated individuals. E17A was associated with
      thymidine analog mutations (TAMs) in reverse transcriptase M41L, L210W and T215Y
      and with the use of didanosine in the patients' treatment histories. E17A had no
      impact on the biochemical and functional properties of Vpr, and did not affect
      kinetics of replication of wild-type or TAMs-containing viruses. However, its
      association with TAMs and the use of didanosine was consistent with phenotypic
      susceptibility assays showing a significant 3-fold decrease in didanosine
      susceptibility of viruses harboring Vpr E17A combined with TAMs compared to
      viruses harboring TAMs alone. CONCLUSION: These findings highlight a novel role
      of Vpr in HIV-1 drug resistance. Vpr E17A confers resistance to didanosine when
      associated with TAMs. Whether Vpr E17A facilitates excision of didanosine is
      still to be determined.

PMID- 22138484
TI  - Deletion of the vaccinia virus F13L gene results in a highly attenuated virus
      that mounts a protective immune response against subsequent vaccinia virus
      challenge.
AB  - Vaccinia virus F13L encodes the envelope protein p37, which is the target of the
      anti-pox virus drug ST-246 (Yang et al., 2005) and that is required for
      production of extracellular vaccinia virus. The F13L (p37)-deleted (and ST-246
      resistant) vaccinia virus recombinant (Vac-DeltaF13L) produced smaller plaques
      than the wild-type vaccinia (Western Reserve vaccinia). In addition, Vac
      DeltaF13L proved, when inoculated either intravenously or intracutaneously in
      both immunocompetent and immunodeficient (athymic nude or SCID) mice, to be
      severely attenuated. Intravenous or intracutaneous inoculation of immunocompetent
      mice with the DeltaF13L virus efficiently protected against a subsequent
      intravenous, intracutaneous or intranasal challenge with vaccinia WR (Western
      Reserve). This was corroborated by the observation that Vac-DeltaF13L induced a
      humoral immune response against vaccinia following either intravenous or
      intracutaneous challenge. In conclusion, F13L-deleted vaccinia virus may have the
      potential to be developed as a smallpox vaccine.

PMID- 22138485
TI  - Purification of hemorrhagic SVMPs from venoms of three vipers of Egypt.
AB  - Three viper P-III hemorrhagic SVMPs: EpyHTI (60 kDa), EcoHTI (60 kDa) and CcHTI
      (58 kDa) of the most dangerous vipers Echis pyramidum, Echis coloratus and
      Cerastes cerastes, respectively were purified and characterized in a set of
      biochemical assays. The SVMPs were purified by applying a protocol of three
      successive chromatographic steps. The enzymatic activity of the purified SVMPs
      was stimulated by the divalent cations Ca2+, Mg2+ and inhibited by
      metalloproteinase inhibitors and (Zn2+, Mn2+, Ni2+, Co2+, Cu2+ and Hg2), whereas
      inhibitors of serine and cysteine proteinases had no effect. The digestion of the
      BM proteins by purified SVMPs was much different, indicating different cleavage
      specificity for each of the purified SVMPs. Based on their intense hemorrhagic
      activity and molecular masses, the purified enzymes were hypothesized to belong
      to the P-III class of SVMPs. The three SVMPs possess close biochemical
      properties, but are different with respect to cleavage site, (fibronectin and
      fibrinogen). Furthermore, the described purification procedure allows simple
      preparation of appreciable quantities of the three SVMPs for further studies.

PMID- 22138486
TI  - Application of allele-specific quantitative PCR using genomic DNA to monitor
      minimal residual disease based on mutant gene levels following allogeneic
      hematopoietic stem cell transplantation in patients with hematological
      malignancies: comparison of mutant levels with autologous DNA percentage by short
      tandem repeat-PCR.
AB  - BACKGROUND: Quantitative evaluation of minimal residual disease (MRD) following
      hematopoietic stem cell transplantation (HSCT) is indispensable for patients with
      hematological malignancies. In addition to established MRD markers such as
      immunoglobulin and T-cell receptor gene rearrangements, fusion genes, or
      aberrantly expressed genes, single nucleotide mutations are considered one of the
      MRD markers that reflect the malignant cell clone. METHODS: We compared the
      quantity of mutant genes by allele-specific quantitative polymerase chain
      reaction (AS-qPCR) for single nucleotide mutations (TP53 410T>A and PTPN11
      1508G>A) with the percentage of autologous DNA by short tandem repeat (STR)-PCR.
      RESULTS: Following HSCT, the quantity of mutant genes detected by AS-qPCR
      correlated with the percentage of autologous DNA assessed by the STR-PCR.
      Moreover, mutant DNAs were detected at a quantifiable level before relapse,
      whereas the percentage of autologous DNA was less than 5%, that is, complete
      chimerism. CONCLUSIONS: The AS-qPCR approach for single nucleotide mutations was
      accurate and highly sensitive for monitoring pre-transplantation as well as post
      transplantation MRD. AS-qPCR for single nucleotide mutation is suitable for
      monitoring MRD in patients who lack previously established MRD markers.

PMID- 22138487
TI  - The NF-Y/p53 liaison: well beyond repression.
AB  - NF-Y is a sequence-specific transcription factor - TF - targeting the common
      CCAAT promoter element. p53 is a master TF controlling the response to stress
      signals endangering genome integrity, often mutated in human cancers. The NF
      Y/p53 - and p63, p73 - interaction results in transcriptional repression of a
      subset of genes within the vast NF-Y regulome under DNA-damage conditions. Recent
      data shows that NF-Y is also involved in pro-apoptotic activities, either
      directly, by mediating p53 transcriptional activation, or indirectly, by being
      targeted by a non coding RNA, PANDA. The picture is subverted in cells carrying
      Gain-of-function mutant p53, through interactions with TopBP1, a protein also
      involved in DNA repair and replication. In summary, the connection between p53
      and NF-Y is crucial in determining cell survival or death.

PMID- 22138488
TI  - Hepatitis C among methadone maintenance treatment patients in Shanghai and
      Kunming, China.
AB  - BACKGROUND: This study aims to: (1) document the prevalence of hepatitis C virus
      (HCV) among methadone maintenance treatment (MMT) patients in Kunming and
      Shanghai; (2) examine risk factors for HCV by comparing those who tested positive
      with those who were negative and (3) examine if HCV serostatus is related to
      attitudes toward MMT. METHODS: Using data collected from 306 patients admitted to
      MMT in 2009-2010 in Shanghai and Kunming, we compared HCV-positive and HCV
      negative patients (based on clinical records) on their HCV knowledge and risk
      behaviors and attitudes toward MMT. RESULTS: The HCV seropositive rate was 53.3%
      (51.3% in Shanghai and 55.5% in Kunming) and a majority of patients did not know
      their serostatus. Patients scored on average fewer than 6 correct out of the 20
      items in the HCV knowledge questionnaire. Recent injection use and length of
      opiate use were strong predictors of HCV status, while no differences were found
      between HCV-positive and HCV-negative individuals in sexual risks or HCV
      knowledge. Both groups expressed similar views toward MMT. CONCLUSION: The high
      HCV prevalence and the general lack of knowledge about HCV infection,
      transmission and treatment suggest the need to provide HCV education and health
      promotion programs among patients in MMT.

PMID- 22138489
TI  - Identifying former injecting drug users infected with hepatitis C: an evaluation
      of a general practice-based case-finding intervention.
AB  - BACKGROUND: In Scotland, a general practice-based case-finding initiative, to
      diagnose and refer hepatitis C virus (HCV) chronically infected former injecting
      drug users (IDUs), was evaluated. METHODS: Testing was offered in eight Glasgow
      general practices in areas of high deprivation and high HCV and IDU prevalence to
      attendees aged 30-54 years with a history of IDU. Test uptake and diagnosis rates
      were compared with those in eight demographically similar control practices.
      RESULTS: Of 422 eligible intervention practice attendees, 218 (52%) were offered
      an HCV test and, of these, 121 (56%) accepted. Poor venous access in 13
      individuals prevented testing. Of 105 tested, 70% (74/105) were antibody positive
      of which 58% (43/74) were RNA positive by PCR. Of 43 chronically infected
      individuals identified in intervention practices, 22 (51%) had attended
      specialist care within 30 months of the study, while 9 (21%) had defaulted. In
      control practices, 8 (22%) of 36 individuals tested were antibody positive. Test
      uptake and case yield were approximately 3 and 10 times higher in intervention
      compared with control practices, respectively. CONCLUSIONS: Targeted case-finding
      in primary care demonstrated higher test uptake and diagnosis rates; however, to
      optimize diagnosis and referral of chronically infected individuals, alternative
      means of testing (e.g. dried blood spots) and retention in specialist care (e.g.
      outreach services) must be explored.

PMID- 22138490
TI  - Burden of disease due to cancer in England and Wales.
AB  - BACKGROUND: This study aims to estimate the burden of cancer in England and Wales
      using disability-adjusted life years (DALYs) and to determine if the ranking of
      relative importance changes with metric used. METHODS: DALYs are the sum of years
      of life lost due to mortality and years lost due to disability. Annual DALYs due
      to cancer were calculated using cancer registration, mortality, disability
      weights and World Health Organization methodology. RESULTS: There were 8 605 362
      DALYs due to cancer (3242 DALYs/100 000 population/year). Of the total, 47%
      corresponded to lung, prostate and colorectal cancers in males and 56% to breast,
      lung, colorectal and ovarian cancers in females. Mortality (86% of DALYs)
      contributed predominantly to DALYs. Individuals of 65-75 years contributed to 28%
      of DALYs. Among females, lung cancer ranked highest by death rates, whereas the
      highest DALYs were from breast cancer. CONCLUSIONS: Highest DALYs were due to
      lung, breast, prostate and colorectal cancers in England and Wales. The addition
      of the disability component changes the relative position of some of the top
      cancers. Although metrics based on deaths alone capture most effects of cancer on
      population health levels, important additional perspectives, relevant to the
      planning of services, can be gained from burden of disease analyses.

PMID- 22138492
TI  - Functionalized nanosystems for targeted mitochondrial delivery.
AB  - Mitochondrial dysfunction including oxidative stress and DNA mutations underlies
      the pathology of various diseases including Alzheimer's disease and diabetes,
      necessitating the development of mitochondria targeted therapeutic agents.
      Nanotechnology offers unique tools and materials to target therapeutic agents to
      mitochondria. As discussed in this paper, a variety of functionalized nanosystems
      including polymeric and metallic nanoparticles as well as liposomes are more
      effective than plain drug and non-functionalized nanosystems in delivering
      therapeutic agents to mitochondria. Although the field is in its infancy, studies
      to date suggest the superior therapeutic activity of functionalized nanosystems
      for treating mitochondrial defects.

PMID- 22138491
TI  - CFTR: folding, misfolding and correcting the DeltaF508 conformational defect.
AB  - Cystic fibrosis (CF), the most common lethal genetic disease in the Caucasian
      population, is caused by loss-of-function mutations of the CF transmembrane
      conductance regulator (CFTR), a cyclic AMP-regulated plasma membrane chloride
      channel. The most common mutation, deletion of phenylalanine 508 (DeltaF508),
      impairs CFTR folding and, consequently, its biosynthetic and endocytic processing
      as well as chloride channel function. Pharmacological treatments may target the
      DeltaF508 CFTR structural defect directly by binding to the mutant protein and/or
      indirectly by altering cellular protein homeostasis (proteostasis) to promote
      DeltaF508 CFTR plasma membrane targeting and stability. This review discusses
      recent basic research aimed at elucidating the structural and trafficking defects
      of DeltaF508 CFTR, a prerequisite for the rational design of CF therapy to
      correct the loss-of-function phenotype.

PMID- 22138493
TI  - Metals in biology: defining metalloproteomes.
AB  - The vital nature of metal uptake and balance in biology is evident in the highly
      evolved strategies to facilitate metal homeostasis in all three domains of life.
      Several decades of study on metals and metalloproteins have revealed numerous
      essential bio-metal functions. Recent advances in mass spectrometry, X-ray
      scattering/absorption, and proteomics have exposed a much broader usage of metals
      in biology than expected. Even elements such as uranium, arsenic, and lead are
      implicated in biological processes as part of an emerging and expansive view of
      bio-metals. Here we discuss opportunities and challenges for established and
      newer approaches to study metalloproteins with a focus on technologies that
      promise to rapidly expand our knowledge of metalloproteins and metal functions in
      biology.

PMID- 22138494
TI  - Bio-based production of chemicals, materials and fuels -Corynebacterium
      glutamicum as versatile cell factory.
AB  - Since their discovery almost 60 years ago, Corynebacterium glutamicum and related
      subspecies are writing a remarkable success story in industrial biotechnology.
      Today, these gram-positive soil bacteria, traditionally well-known as excellent
      producers of L-amino acids are becoming flexible, efficient production platforms
      for various chemicals, materials and fuels. This development is intensively
      driven by systems metabolic engineering concepts integrating systems biology and
      synthetic biology into strain engineering.

PMID- 22138495
TI  - Single cell Raman spectroscopy for cell sorting and imaging.
AB  - Single cell Raman spectroscopy (SCRS) is a non-invasive and label-free
      technology, allowing in vivo and multiple parameter analysis of individual living
      cells. A single cell Raman spectrum usually contains more than 1000 Raman bands
      which provide rich and intrinsic information of the cell (e.g. nucleic acids,
      protein, carbohydrates and lipids), reflecting cellular genotypes, phenotypes and
      physiological states. A Raman spectrum serves as a molecular 'fingerprint' of a
      single cell, making it possible to differentiate various cells including
      bacterial, protistan and animal cells without prior knowledge of the cells.
      However, a key drawback of SCRS is the fact that spontaneous Raman signals are
      naturally weak; this review discusses recent research progress in significantly
      enhancing and improving the signal of spontaneous Raman spectroscopy, including
      resonance Raman spectroscopy (RRS), coherent anti-Stokes Raman spectroscopy
      (CARS), stimulated Raman spectroscopy (SRS) and surface enhanced Raman scattering
      (SERS). This review focuses on the biotechnological development and the
      associated applications of SCRS, including Raman activated cell sorting (RACS)
      and Raman imaging and mapping.

PMID- 22138496
TI  - Genetic backgrounds of the Plasmodium falciparum chloroquine resistant
      transporter (pfcrt) alleles in Pakistan.
AB  - Chloroquine (CQ) resistance in Plasmodium falciparum has been associated with
      point mutations in the P. falciparum CQ resistance transporter gene (pfcrt).
      Previous studies have shown 4-5 independent origins for CQ resistant pfcrt
      alleles globally, two in South America, one each in Southeast Asia, Papua New
      Guinea (PNG) and Philippines. In Asia, at least two different alleles
      corresponding to amino acids 72-76 (CVIET and SVMNT) have been found. The CVIET
      allele originated in Southeast Asia and then spread to Asia and Africa as well.
      The SVMNT allele, originating from PNG, has been found in India. This study was
      undertaken to investigate the genetic background of the CQ resistant pfcrt
      haplotypes in Pakistan. We genotyped microsatellite markers surrounding the pfcrt
      gene (six different markers at -12.3, -4.8, -1, 1.5, 3.9, 18.8 kb) in 114
      clinical isolates of P. falciparum collected from different regions in Pakistan.
      Microsatellite analysis showed a significant reduction in genetic variation among
      the mutant SVMNT pfcrt alleles when compared to wild type alleles. The
      predominant SVMNT haplotype found in this study shared the same microsatellite
      haplotype found in both PNG and India. Two isolates with CVIET haplotypes showed
      similar microsatellite background to those found in Africa and Asia. In
      conclusion, this study suggests that CQ resistant SVMNT haplotypes in India and
      Pakistan have a common ancestral origin similar to that of Papua New Guinean
      isolates.

PMID- 22138497
TI  - Implicit and explicit olfactory memory in people with and without Down syndrome.
AB  - This study examined differences in implicit and explicit memory performance
      between people with Down syndrome (DS), their siblings, children matched on
      mental age, and university undergraduates, using olfactory stimuli. The DS and
      mental-age matched participants were also compared on two tasks of executive
      function. The data revealed implicit memory for olfactory stimuli. Further,
      people with DS performed similarly to each control group on the implicit memory
      task, but performed significantly poorer than all control groups on the explicit
      memory task. Impairment to executive functioning was identified as a possible
      cause of this deficit in explicit memory as people with DS performed more poorly
      than the mental-age matched controls on both tasks of executive function.

PMID- 22138499
TI  - Are mesenchymal stem cells major sources of safe signals in immune system?
AB  - Numerous reports have shown that mesenchymal stem cells (MSCs) are implicated in
      immuno-regulation. Several factors expressed from MSCs, especially indoleamine
      2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2), are of importance in immuno
      regulation on immune cells. In current minireview, we provided evidences to
      support a novel notion that MSCs may be a major source of "safe signals" in the
      immune system to balance "dangerous signals" based on a well accepted theory of
      "danger model". Furthermore, MSCs are of lifecycle characterized by age-and
      diseased-related changes, such as decreased growth rate, increased senescence,
      and altered morphology. Thus, defected and abnormal MSCs are implicated in auto
      immune diseases, such as systemic lupus erythematosus (SLE). Clinically, it is
      important to determine clinical benefits and sides effects of cell therapies
      using autologous self-MSCs or healthy allogeneic MSCs in treatment of autoimmune
      diseases.

PMID- 22138498
TI  - Modulation of TCRbeta surface expression during TCR revision.
AB  - TCR revision is a tolerance mechanism by which self-reactive TCRs expressed by
      mature CD4(+) peripheral T cells are replaced by receptors encoded by genes
      generated by post-thymic DNA rearrangement. The downmodulation of surface TCR
      expression initiates TCR revision, and serves as a likely trigger for the
      induction of the recombinase machinery. We show here in a Vbeta5 transgenic mouse
      model system that downregulation of the self-reactive transgene-encoded TCR is
      not maintained by transgene loss or diminished transcription or translation. The
      downregulation of surface TCR expression likely occurs in two stages, only one of
      which requires tolerogen expression.

PMID- 22138500
TI  - Vascular and cellular events in post-mastectomy seroma: an immunohistochemical
      study.
AB  - This study aimed to describe the vascular and cellular histopathological changes
      that occurred in post-mastectomy seroma in an animal model. Unilateral
      mastectomies were conducted on 45 female albino rabbits. On day seven, the skin
      flap and the underlying tissues of the mastectomy regions were dissected and
      processed for histopathological examination using immunohistochemical staining of
      the T- and B-lymphocytes and macrophages (CD3, CD20, and CD68 respectively), and
      the vascular endothelia. The post-mastectomy regions in the seroma group showed a
      large number of inflammatory cells and newly formed blood vessels that lost the
      integrity of their endothelial cell linings, as revealed by the von Willebrand
      factor staining, as well the basement membrane, as revealed by the histochemical
      stain. The post-mastectomy seroma beds showed many CD3 and CD20+ve lymphocytes
      and CD68+ve macrophages. These macrophages were producing angiogenic factors,
      resulting in the persistent and continuous formation of new blood vessels. These
      new blood vessels were defective and represented an underlying cause of seroma
      formation.

PMID- 22138501
TI  - One-year visual outcomes and patient satisfaction after surgical correction of
      presbyopia with an intracorneal inlay of a new design.
AB  - PURPOSE: To evaluate the safety and efficacy of the third-generation Kamra
      corneal inlay (ACI 7000PDT) implanted monocularly in corneal pockets of
      emmetropic presbyopic patients to improve near and intermediate vision. SETTING:
      University Eye Clinic, Paracelsus Medical University, Salzburg, Austria. DESIGN:
      Cohort study. METHODS: The corneal inlay was implanted in the nondominant eye
      over the line of sight by creating a corneal pocket with a femtosecond laser. The
      minimum postoperative follow-up was 12 months. Distance, intermediate, and near
      visual acuities were assessed over the follow-up. Other examinations included
      slitlamp evaluation, central keratometry, computerized corneal topography,
      endothelial cell count, and central corneal thickness. Patients completed
      satisfaction questionnaires preoperatively and 3, 6, and 12 months
      postoperatively. RESULTS: The study evaluated 24 patients. After a mean follow-up
      of 12 months, 92% of patients read Jaeger (J) 3 or better with the surgical eye,
      the mean binocular uncorrected near visual acuity improved from J5 preoperatively
      to J2, and the mean binocular uncorrected intermediate visual acuity was 20/20
      (67% >= 20/20). At 12 months, the mean uncorrected distance visual acuity was
      20/20 in the surgical eye and 20/16 binocularly. Patients reported no change in
      distance vision, and their need for reading glasses decreased significantly
      (P<.001). No inlay was explanted and or recentered during the reported follow-up.
      CONCLUSION: The new corneal inlay was a safe and effective treatment for
      presbyopia over a 1-year follow-up.

PMID- 22138502
TI  - Mycobacterium indicus pranii downregulates MMP-9 and iNOS through COX-2 dependent
      and TNF-alpha independent pathway in mouse peritoneal macrophages in vitro.
AB  - Despite the popular belief that granulomas are innate immune mechanism to
      restrict mycobacterial growth, evidences suggest that granulomas facilitate
      growth of Mycobacterium by recruiting large numbers of uninfected macrophages to
      the site of infection. Matrix metalloproteinase-9 (MMP-9) has been shown to be
      directly involved in recruitment of macrophages at the site of infection,
      contributing to nascent granuloma maturation and bacterial growth. In this
      manuscript it is reported that heat-killed Mycobacterium indicus pranii (MIP)
      leads to a significant downregulation of MMP-9 in murine peritoneal macrophages
      in vitro. The downregulation of MMP-9 is mediated through cyclooxygenase-2 (COX
      2), but independent of tumor necrosis factor-alpha (TNF-alpha). By limiting
      nuclear to cytoplasmic export of COX-2 and iNOS transcripts, MIP inhibits
      excessively-high levels of nitric oxide which can be damaging to the host during
      acute phases of infection. MIP has been shown to provide clinical improvement in
      all phases of leprosy and used for treatment of leprosy and tuberculosis.

PMID- 22138504
TI  - Heart failure services in the United Kingdom: rethinking the machine bureaucracy.
AB  - Poor outcomes and poor uptake of evidence based therapies persist for patients
      with heart failure in the United Kingdom. We offer a strategic analysis of
      services, defining the context, organization and objectives of the service,
      before focusing on implementation and performance. Critical flaws in past service
      development and performance are apparent, a consequence of failed performance
      management, policy and political initiative. The barriers to change and potential
      solutions are common to many health care systems. Integration, information,
      financing, incentives, innovation and values: all must be challenged and improved
      if heart failure services are to succeed. Modern healthcare requires open
      adaptive systems, continually learning and improving. The system also needs
      controls. Performance indicators should be simple, clinically relevant, and
      outcome focused. Heart failure presents one of the greatest opportunities to
      improve symptoms and survival with existing technology. To do so, heart failure
      services require radical reorganization.

PMID- 22138503
TI  - Abnormalities in thalamic neurophysiology in schizophrenia: could psychosis be a
      result of potassium channel dysfunction?
AB  - Psychosis in schizophrenia is associated with source-monitoring deficits whereby
      self-initiated behaviors become attributed to outside sources. One of the
      proposed functions of the thalamus is to adjust sensory responsiveness in
      accordance with the behavioral contextual cues. The thalamus is markedly affected
      in schizophrenia, and thalamic dysfunction may here result in reduced ability to
      adjust sensory responsiveness to ongoing behavior. One of the ways in which the
      thalamus accomplishes the adjustment of sensory processing is by a
      neurophysiological shift to post-inhibitory burst firing mode prior to and during
      certain exploratory actions. Reduced amount of thalamic burst firing may result
      from increased neuronal excitability secondary to a reported potassium channel
      dysfunction in schizophrenia. Pharmacological agents that reduce the excitability
      of thalamic cells and thereby promote burst firing by and large tend to have
      antipsychotic effects.

PMID- 22138505
TI  - Effects of noradrenaline and serotonin depletions on the neuronal activity of
      globus pallidus and substantia nigra pars reticulata in experimental
      parkinsonism.
AB  - Parkinson's disease (PD) is characterized by a degeneration of dopaminergic
      neurons and also by a degradation of noradrenergic neurons from the locus
      coeruleus and serotonergic neurons from the dorsal raphe. However, the effect of
      these depletions on the neuronal activity of basal ganglia nuclei is still
      unknown. By using extracellular single-unit recordings, we have addressed this
      question by testing the effects of selective depletions of noradrenaline (NA)
      (with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4)) and
      serotonin (5-HT) (with 4-chloro-l-phenylalanine (pCPA)) on the neuronal activity
      of globus pallidus (GP) and substantia nigra pars reticulata (SNr) neurons in the
      6-hydroxydopamine (6-OHDA) rat model of PD and sham-lesioned rats. We showed that
      6-OHDA-induced dopamine (DA) depletion resulted in an increased number of GP and
      SNr neurons discharging in a bursty and irregular manner, confirming previous
      studies. These pattern changes were region-dependently influenced by additional
      monoamine depletion. Although the number of irregular and bursty neurons in 6
      OHDA rats tended to decrease in the GP after NA depletion, it did not change
      after pCPA treatment in both GP and SNr. Furthermore, a significant interaction
      between DA and 5-HT depletions was observed on the firing rate of SNr neurons. By
      themselves, NA depletion did not change GP or SNr neuronal activity, whereas 5-HT
      depletion decreased the firing rate and increased the proportion of bursty and
      irregular neurons in both brain regions, suggesting that 5-HT, but not NA, plays
      a major role in the modulation of both the firing rate and patterns of GP and SNr
      neurons. Finally, our data suggest that, in addition to the primary role of DA in
      the control of basal ganglia activity, NA and 5-HT depletion also contribute to
      the dysregulation of the basal ganglia in PD by changes to neuronal firing
      patterns.

PMID- 22138507
TI  - Behavioral profiling of zebrafish embryos exposed to a panel of 60 water-soluble
      compounds.
AB  - The zebrafish is a powerful whole animal model which is complementary to in vitro
      and mammalian models. It has been shown to be applicable to the high-throughput
      behavioral screening of compound libraries. We have analysed 60 water-soluble
      toxic compounds covering a range of common drugs, toxins and chemicals, and
      representing various pharmacological mechanisms. Wild-type zebrafish larvae were
      cultured individually in defined buffer in 96 well plates. They were exposed for
      a 96h period starting at 24h post fertilization (hpf). A logarithmic
      concentration series was used for range-finding, followed by a narrower geometric
      series for LC(50) determination. LC(50) values were determined at 24h intervals
      and behavioral testing was carried out on day 5. We used the visual motor
      response test, in which movement of individual larvae was analysed using
      automated video-tracking. For all compounds, LC(50) values were found to decrease
      as the embryo developed. The majority of compounds (57/60) produced an effect in
      both the basal (lights on) and challenge phases (lights off) of the behavioral
      assay. These effects were either (i) suppression of locomotor activity (monotonic
      concentration-response); (ii) stimulation then suppression (biphasic response);
      (iii) stimulation (monotonic response). We conclude that behavioral assays with
      zebrafish embryos could be useful for pharmaceutical efficacy and toxicity
      screening. The precise phenotypic outcome obtained with behavioral assay varies
      with compound class.

PMID- 22138506
TI  - Normal mitral cell dendritic development in the setting of Mecp2 mutation.
AB  - Rett syndrome (RTT) is an autism spectrum disorder caused by mutation in the gene
      encoding methyl CpG binding protein 2 (MECP2). Evidence to date suggests that
      these disorders display defects in synaptic organization and plasticity. A
      hallmark of the pathology in RTT has been identified as decreased dendritic
      arborization, which has been interpreted to represent abnormal dendritic
      formation and pruning during development. Our previous studies revealed that
      olfactory axons display defective pathfinding and targeting in the setting of
      Mecp2 mutation. In the present work, we use Mecp2 mutant mouse models and the
      olfactory system to investigate dendritic development. Here, we demonstrate that
      mitral cell dendritic development proceeds normally in mutant mice, resulting in
      typical dendritic morphology at early postnatal ages. We also failed to detect
      abnormalities in dendritic inputs at symptomatic stages when glomeruli from
      mutant mice appear smaller in area than the wild type (WT) (6 weeks postnatally).
      Collectively, these findings suggest that the initial defects in glomeruli
      impairment seen with Mecp2 mutation do not result from abnormal dendritic
      development. Our results using the olfactory system indicate that dendritic
      abnormalities are not an early feature in the abnormalities incurred by Mecp2
      mutation.

PMID- 22138508
TI  - Order and disorder: temporal organization of eating.
AB  - Feeding behavior is described from an evolutionary perspective, and implications
      for modern neurobiological studies are suggested. In particular, it is argued
      that meals may have evolved more for sociocultural reasons than physiological
      imperatives, and that biological approaches to the study of feeding episodes
      should adopt a more flexible model that is founded in economic or cost-benefit
      considerations. Specific examples of flexibility in mouse feeding behavior are
      given. It is further argued that the modern human food environment is so
      immoderate that physiological manipulations designed to restrain eating have
      little hope of achieving this goal.

PMID- 22138509
TI  - Environmental enrichment improves recent but not remote memory in association
      with a modified brain metabolic activation profile in adult mice.
AB  - Environmental enrichment is known to improve learning and memory in adult
      rodents. Whereas the morphological changes underlying these beneficial effects
      are well documented, few studies have addressed the influence of this housing
      condition on the neuronal networks underlying memory processes. We assessed the
      effects of environmental enrichment on behavioural performances and brain
      metabolic activation during a memory task in mice. Adult mice were housed in
      standard (SC) or enriched (EC) conditions for 3 weeks. Then, recent and remote
      memory performances were measured in the passive avoidance test. After testing,
      brain metabolic activation was assessed through cytochrome oxidase (CO) activity.
      EC improved recent memory, in association with an increased metabolic activation
      in the frontal and prefrontal cortices and a decreased activation in the baso
      lateral amygdala and the hippocampus. EC did not improve remote memory, and
      globally decreased CO activity. Our findings suggest the involvement of regions
      of pivotal importance during recent memory, such as the frontal cortex, in the
      beneficial effects of EC.

PMID- 22138510
TI  - Human FcgammaRIIA induces anaphylactic and allergic reactions.
AB  - IgE and IgE receptors (FcepsilonRI) are well-known inducers of allergy. We
      recently found in mice that active systemic anaphylaxis depends on IgG and IgG
      receptors (FcgammaRIIIA and FcgammaRIV) expressed by neutrophils, rather than on
      IgE and FcepsilonRI expressed by mast cells and basophils. In humans,
      neutrophils, mast cells, basophils, and eosinophils do not express FcgammaRIIIA
      or FcgammaRIV, but FcgammaRIIA. We therefore investigated the possible role of
      FcgammaRIIA in allergy by generating novel FcgammaRIIA-transgenic mice, in which
      various models of allergic reactions induced by IgG could be studied. In mice,
      FcgammaRIIA was sufficient to trigger active and passive anaphylaxis, and airway
      inflammation in vivo. Blocking FcgammaRIIA in vivo abolished these reactions. We
      identified mast cells to be responsible for FcgammaRIIA-dependent passive
      cutaneous anaphylaxis, and monocytes/macrophages and neutrophils to be
      responsible for FcgammaRIIA-dependent passive systemic anaphylaxis. Supporting
      these findings, human mast cells, monocytes and neutrophils produced
      anaphylactogenic mediators after FcgammaRIIA engagement. IgG and FcgammaRIIA may
      therefore contribute to allergic and anaphylactic reactions in humans.

PMID- 22138511
TI  - CBL mutation in chronic myelomonocytic leukemia secondary to familial platelet
      disorder with propensity to develop acute myeloid leukemia (FPD/AML).
AB  - Familial platelet disorder with a propensity to develop acute myeloid leukemia
      (FPD/AML) is a rare autosomal dominant disease characterized by thrombocytopenia,
      abnormal platelet function, and a propensity to develop myelodysplastic syndrome
      (MDS) and AML. So far, > 20 affected families have been reported. Recently, a
      second RUNX1 alteration has been reported; however, no additional molecular
      abnormalities have been found so far. We identified an acquired CBL mutation and
      11q-acquired uniparental disomy (11q-aUPD) in a patient with chronic
      myelomonocytic leukemia (CMML) secondary to FPD with RUNX1 mutation but not in
      the same patient during refractory cytopenia. This finding suggests that
      alterations of the CBL gene and RUNX1 gene may cooperate in the pathogenesis of
      CMML in patients with FPD/AML. The presence of CBL mutations and 11q-aUPD was an
      important "second hit" that could be an indicator of leukemic transformation of
      MDS or AML in patients with FPD/AML.

PMID- 22138513
TI  - Phagocytosis by macrophages and endothelial cells inhibits procoagulant and
      fibrinolytic activity of acute promyelocytic leukemia cells.
AB  - The coagulopathy of acute promyelocytic leukemia (APL) is mainly related to
      procoagulant substances and fibrinolytic activators of APL blasts, but the fate
      of these leukemic cells is unknown. The aim of this study was to investigate the
      removal of APL blasts by macrophages and endothelial cells in vitro and
      consequent procoagulant and fibrinolytic activity of APL cells. We found that
      human umbilical vein endothelial cells as well as THP-1 and monocyte-derived
      macrophages bound, engulfed, and subsequently degraded immortalized APL cell line
      NB4 and primary APL cells. Lactadherin promoted phagocytosis of APL cells in a
      time-dependent fashion. Furthermore, factor Xa and prothrombinase activity of
      phosphatidylserine-exposed target APL cells was time-dependently decreased after
      incubation with phagocytes (THP-1-derived macrophages or HUVECs). Thrombin
      production on target APL cells was reduced by 40%-45% after 2 hours of
      coincubation with phagocytes and 80% by a combination of lactadherin and
      phagocytes. Moreover, plasmin generation of target APL cells was inhibited 30% by
      2 hours of phagocytosis and ~ 50% by lactadherin-mediated engulfment. These
      results suggest that engulfment by macrophages and endothelial cells reduce
      procoagulant and fibrinolytic activity of APL blasts. Lactadherin and
      phagocytosis could cooperatively ameliorate the clotting disorders in APL.

PMID- 22138512
TI  - Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven
      EBV+ lymphomas after allogeneic hematopoietic cell transplantation.
AB  - We evaluated HLA-compatible donor leukocyte infusions (DLIs) and HLA-compatible
      or HLA-disparate EBV-specific T cells (EBV-CTLs) in 49 hematopoietic cell
      transplantation recipients with biopsy-proven EBV-lymphoproliferative disease
      (EBV-LPD). DLIs and EBV-CTLs each induced durable complete or partial remissions
      in 73% and 68% of treated patients including 74% and 72% of patients surviving >=
      8 days after infusion, respectively. Reversible acute GVHD occurred in recipients
      of DLIs (17%) but not EBV-CTLs. The probability of complete response was
      significantly lower among patients with multiorgan involvement. In responders,
      DLIs and EBV-CTLs regularly induced exponential increases in EBV-specific CTL
      precursor (EBV-CTLp) frequencies within 7-14 days, with subsequent clearance of
      EBV viremia and resolution of disease. In nonresponders, EBV-CTLps did not
      increase and EBV viremia persisted. Treatment failures were correlated with
      impaired T-cell recognition of tumor targets. Either donor-derived EBV-CTLs that
      had been sensitized with autologous BLCLs transformed by EBV strain B95.8 could
      not lyse spontaneous donor-derived EBV-transformed BLCLs expanded from the
      patient's blood or biopsied tumor or they failed to lyse their targets because
      they were selectively restricted by HLA alleles not shared by the EBV-LPD.
      Therefore, either unselected DLIs or EBV-specific CTLs can eradicate both
      untreated and Rituxan-resistant lymphomatous EBV-LPD, with failures ascribable to
      impaired T-cell recognition of tumor-associated viral antigens or their
      presenting HLA alleles.

PMID- 22138514
TI  - Functional characterization of CD4+ T cells in aplastic anemia.
AB  - The role of CD4(+) T cells in the pathogenesis of aplastic anemia (AA) is not
      well characterized. We investigate CD4(+) T-cell subsets in AA. Sixty-three
      patients with acquired AA were studied. Th1 and Th2 cells were significantly
      higher in AA patients than in healthy donors (HDs; P = .03 and P = .006). Tregs
      were significantly lower in patients with severe AA than in HDs (P < .001) and
      patients with non-severe AA (P = .01). Th17 cells were increased in severe AA (P
      = .02) but normal in non-severe AA. Activated and resting Tregs were reduced in
      AA (P = .004; P = .01), whereas cytokine-secreting non-Tregs were increased (P =
      .003). Tregs from AA patients were unable to suppress normal effector T cells. In
      contrast, AA effector T cells were suppressible by Tregs from HDs. Th1 clonality
      in AA, investigated by high-throughput sequencing, was greater than in HDs (P =
      .03). Our results confirm that Th1 and Th2 cells are expanded and Tregs are
      functionally abnormal in AA. The clonally restricted expansion of Th1 cells is
      most likely to be antigen-driven, and induces an inflammatory environment, that
      exacerbate the functional impairment of Tregs, which are reduced in number.

PMID- 22138515
TI  - Effects of intra-abdominal pressure on respiratory system mechanics in
      mechanically ventilated rats.
AB  - We investigated the effects of intra-abdominal pressure on respiratory system
      compliance at different PEEP levels. 20 ventilated rats underwent four pressure
      levels (7, 9, 11, 13 mm Hg) of helium pneumoperitoneum and were allocated to one
      of the four PEEP groups (0, 3, 6 and 9 cm H(2)O). From the expiratory pressure
      volume curve the mathematical inflection point (MIP) was calculated. Volume
      dependent compliance was analyzed using the SLICE-method. MIP-pressure correlated
      to the intra-abdominal pressure (r(2)=0.94, p<0.001). Peak inspiratory pressure
      increased with intra-abdominal pressure, and was lower after recruitment
      maneuvers (p<0.001). The compliance gain following recruitment-maneuvers depended
      on PEEP, intra-abdominal pressure and intratidal volume (all p<0.001). Mean
      arterial pressure was independent of PEEP (p=0.068) and intra-abdominal pressure
      (p=0.293). Volume-dependent compliance courses varied according to PEEP and intra
      abdominal pressure. The level of intra-abdominal pressure alters respiratory
      system mechanics in healthy lungs. Intratidal compliance can be used to guide the
      PEEP adjustment in intra-abdominal hypertension. If counterbalanced by PEEP,
      elevated intra-abdominal pressure has no negative effects on oxygenation or
      hemodynamics.

PMID- 22138516
TI  - The apoptosis inducing effect of Glycosmis pentaphylla (Retz.) Correa and its
      influence on gene expression in hepatocellular carcinoma cell line, Hep3 B.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Glycosmis pentaphylla (Retz.) Correa is used in
      Indian traditional medicine against jaundice and other liver disorders. AIM OF
      THE STUDY: The study aims to determine the in vitro anticancer and apoptosis
      inducing activity of Glycosmis pentaphylla in hepatocellular carcinoma cell line,
      Hep3 B. MATERIALS AND METHODS: The cytotoxic and apoptosis inducing activity of
      the crude extract and active fractions were estimated on Hep3 B and RAW264.7 cell
      lines by MTT assay, Hoechst staining, DNA fragmentation, morphological studies,
      reverse transcription polymerase chain reaction and anti-poly-(ADP-ribose)
      polymerase assays. The phytochemical profiling of active extract was done by TLC
      and HPTLC methods. RESULTS: Ethanol extract of Glycosmis pentaphylla was more
      effective than other extracts in reducing the proliferation of Hep3 B cells. As
      revealed by the results from DNA fragmentation, Hoechst staining, morphological
      studies, RT-PCR, PARP cleavage and gene expression studies, active extract
      induced apoptosis on Hep3 B cell line in concentration and time dependent manner
      with increase in the Bax/Bcl2 gene expression ratio. Chemo profiling data
      revealed the presence of flavonoid in the active fraction. CONCLUSIONS: The study
      showed that major active component in the ethanol extract of Glycosmis
      pentaphylla is a flavonoid which induces apoptosis on cancer cell line, Hep3 B,
      by increasing the expression ratio of Bax/Bcl2 genes in a time and dose dependent
      manner.

PMID- 22138517
TI  - Toxicological evaluation of the aqueous leaf extract of Moringa oleifera Lam.
      (Moringaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The rapid increase in consumption of herbal
      remedies worldwide has been stimulated by several factors, including the notion
      that all herbal products are safe and effective. However, over the past decade,
      several news-catching episodes in developed communities indicated adverse
      effects, sometimes life-threatening, allegedly arising as a consequence to taking
      herbal products or traditional medicines from various ethnic groups. Despite the
      popular use of Moringa oleifera for treating various disorders, there is limited
      or no scientific data available regarding safety aspects of this remedy, nor are
      there any documented toxicological studies that can be used to ascertain the
      safety index of its herbal preparation. Therefore, this present study aimed to
      carry out extensive toxicological evaluation of the aqueous leaf extract of
      Moringa oleifera. MATERIALS AND METHODS: In an acute toxicity test, male Wistar
      albino mice were orally administered an aqueous extract up to 6400 mg/kg and
      intraperitoneally up to 2000 mg/kg. A sub-chronic toxicity test was performed by
      daily administration with the extract at 250, 500 and 1500 mg/kg orally for 60
      days. Control rats received distilled water. Sperm quality was analyzed,
      haematological and biochemical (liver enzymes, urea and creatinine) parameters
      were determined and a histopathological examination was carried out. RESULTS: The
      LD(50) was estimated to be 1585 mg/kg. The extract did not elicit any significant
      difference (P>=0.05) in sperm quality, haematological and biochemical parameters
      in the treated rats compared to the control. Moreover, there was no significant
      difference in weight gain of the control and treated animals although there was a
      dose-dependent reduction in food consumption of the animals treated with 250 to
      1500 mg/kg extract. CONCLUSIONS: Results obtained in this study suggest that the
      aqueous leaf extract of Moringa oleifera is relatively safe when administered
      orally.

PMID- 22138518
TI  - Cardioprotective effect of water and ethanol extract of Salvia miltiorrhiza in an
      experimental model of myocardial infarction.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza has long been used in the
      traditional Chinese formulations for the treatment of heart ischemic diseases.
      AIM OF THE STUDY: We investigated the cardioprotective effect of purified Salvia
      miltiorrhiza extract (SME) in an experimental model of acute myocardial
      infarction. MATERIALS AND METHODS: Following induction of acute myocardial
      infarction in rats by adminstration of isoproterenol, hemodynamic and
      electrocardiographic parameters were monitored and recorded continuously, cardiac
      enzymes and parameters of oxidative stress were measured, and histopathological
      examination of heart tissue was performed. Experiments were performed in rats
      treated with SME or vehicle, as well as in those treated with Fufang Danshen
      Tablet (FDT) as a positive control which has previously been shown to prevent
      myocardial ischemia. RESULTS: Isoproterenol-treated rats showed reductions in
      left ventricular systolic pressure as well as in maximum and minimum rate of
      developed left ventricular pressure, together with an increase in left
      ventricular end-diastolic pressure. They also demonstrated ST-segment elevation,
      together with increases in serum levels of lactate dehydrogenase, glutamic
      oxalacetic transaminase, creatine kinase and malondialdehyde, as well as
      decreases in serum activities of glutathione peroxidase and superoxide dismutase.
      Oral administration of SME (29.76 or 59.52 mg/kg) blunted all of the hemodynamic
      and biochemical changes induced by isoproterenol, as did FDT (1210 mg/kg). The
      protective effect of SME on isoproterenol-induced myocardial damage was further
      confirmed by histopathological examination. CONCLUSIONS: Our results suggest that
      SME affords protection against isoproterenol-induced myocardial infarction.

PMID- 22138519
TI  - Rapid and reliable genotyping of HLA-B*27 in the Chinese Han population using a
      duplex real-time TaqMan PCR assay.
AB  - OBJECTIVES: To develop a duplex real-time TaqMan PCR assay for genotyping HLA
      B*27 in the Chinese Han population. DESIGN AND METHODS: A standard curve was
      constituted to deduce amplification efficiency, dynamic range and detection limit
      of the duplex real-time TaqMan PCR assay, whereas PCR-SBT (PCR with sequence
      based typing) was used to evaluate the accuracy of the assay. RESULTS: A linear
      standard curve for determining HLA-B*27 was obtained within the range of 10(1)
      10(9) copies per reaction with the correlation coefficient of 0.99 and
      amplification efficiency of 98.30%. The detection limit was 3.09 copies per
      reaction. Complete concordance was found between the results obtained by the
      duplex real-time TaqMan PCR assay and PCR-SBT. Fifty-nine of the 178 genomic
      samples were HLA-B*27 positive and the other 119 were HLA-B*27 negative.
      CONCLUSIONS: The duplex real-time TaqMan PCR approach appears to be a reliable,
      sensitive, rapid and high-throughput method to genotype HLA-B*27 in the Chinese
      Han population.

PMID- 22138521
TI  - Prospective randomized trial of multiple micronutrients in subfertile women
      undergoing ovulation induction: a pilot study.
AB  - This study investigated whether subfertile women undergoing ovulation induction
      using standard treatment regimens with clomiphene citrate/gonadotrophins have
      higher pregnancy rates when on an adjuvant multiple micronutrient (MMN)
      nutritional supplement compared with folic acid alone. A prospective randomized
      controlled trial was conducted in a teaching-hospital fertility clinic on 58
      subfertile women, of which 56 women completed the study. Women undergoing
      ovulation induction were allocated to either receive adjuvant MMN supplementation
      or folic acid. Clinical pregnancy rates and blood nutrient concentrations were
      assessed after the third treatment attempt or as soon as the women achieved
      pregnancy. Using intention-to-treat analysis, it was observed that women on
      adjuvant MMN supplementation had a significantly higher cumulative clinical
      pregnancy rate (66.7%) compared with those on folic acid (39.3%; P = 0.013). The
      ongoing pregnancy rate in women on MMN supplementation was 60.0% versus 25.0% (P
      < 0.02) in the folic-acid group. Further, women who were on MMN supplementation
      had significantly fewer attempts to achieve pregnancy compared with women on
      folic acid (P < 0.001). The results of this pilot study suggest that women who
      take adjuvant MMN supplementation during ovulation induction have a higher chance
      of pregnancy compared with women on folic acid.

PMID- 22138522
TI  - Curcumin attenuates Concanavalin A-induced liver injury in mice by inhibition of
      Toll-like receptor (TLR) 2, TLR4 and TLR9 expression.
AB  - Curcumin has antiviral, antioxidant, and anti-inflammatory properties. However,
      the hepatoprotective effects and molecular mechanisms of curcumin on acute liver
      injury have not been carefully examined. The aims of this study were to examine
      the anti-inflammatory effect of curcumin on Concanavalin A (Con A) induced
      hepatitis, and to elucidate its underlying molecular mechanisms in mice. Mice
      received curcumin (200 mg/kg body weight) by gavage before Con A intravenous
      administration. We found that curcumin pretreatment was able to significantly
      reduce the elevated plasma aminotransferase levels and liver necrosis in Con A
      induced hepatitis. Also, curcumin pretreatment reduced intrahepatic expression of
      genes encoding pro-inflammatory molecules such as tumor necrosis factor alpha
      (TNF-alpha) and interferon gamma (IFN-gamma) as compared with the vehicle
      controls, but augmented anti-inflammatory cytokine interleukin 10 (IL-10) by
      enzyme linked immunosorbent assay (ELISA). Furthermore, the expression levels of
      Toll-like receptor (TLR) 2, TLR4 and TLR9 mRNA or protein in liver tissues were
      significantly lowered by curcumin treatment. Curcumin pretreatment did not affect
      hepatic Kupffer cell numbers after Con A injection. These results suggest that
      curcumin pretreatment protects against T cell-mediated hepatitis in mice. The
      beneficial effect of curcumin may be partly mediated by inhibiting the expression
      levels of TLR2, TLR4 and TLR9 in the liver.

PMID- 22138520
TI  - Nuclear factor erythroid-derived factor 2-related factor 2 regulates
      transcription of CCAAT/enhancer-binding protein beta during adipogenesis.
AB  - Nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) is a cap-n
      collar basic leucine zipper transcription factor that is involved in the cellular
      adaptive response to oxidative stress. Our previous study reported that targeted
      disruption of the Nrf2 gene in mice decreases adipose tissue mass and protects
      against obesity induced by a high-fat diet. Deficiency of Nrf2 in preadipocytes
      and mouse embryonic fibroblasts led to impaired adipogenesis. Consistent with
      these findings, the current study found that lack of Nrf2 in primary cultured
      mouse preadipocytes and 3T3-L1 cells hampered adipogenic differentiation induced
      by hormonal cocktails. Stable knockdown of Nrf2 in 3T3-L1 cells blocked the
      enhanced adipogenesis caused by deficiency of kelch-like ECH-associated protein 1
      (Keap1), a Cul3-adapter protein that allows for Nrf2 to be ubiquinated and
      degraded by the 26S protesome complex. In addition, increased production of
      reactive oxygen species (ROS) and activation of Nrf2 occurred at the very early
      stage upon adipogenic hormonal challenge in 3T3-L1 cells, followed by an
      immediate induction of CCAAT/enhancer-binding protein beta (C/EBPbeta). Knockdown
      of Nrf2 led to reduced expression of C/EBPbeta induced by adipogenic hormonal
      cocktails, chemical Nrf2 activators or Keap1 silencing. Cebpbeta promoter-driven
      reporter assays and chromatin immunoprecipitation suggested that Nrf2 associates
      with a consensus antioxidant response element (ARE) binding site in the promoter
      of the Cebpbeta gene during adipogenesis and upregulates its expression. These
      findings demonstrate a novel role of Nrf2 beyond xenobiotic detoxification and
      antioxidant response, and suggest that Nrf2 is one of the transcription factors
      that control the early events of adipogenesis by regulating expression of
      Cebpbeta.

PMID- 22138524
TI  - Multidisciplinary management of an obstetric patient with glycogen storage
      disease type 3.
AB  - A 22-year-old primiparous woman with known glycogen storage disease type 3a
      presented to our hospital during her 12th week of pregnancy. Glycogen storage
      disease type 3 is a rare inherited disorder resulting from a deficiency of the
      glycogen debranching enzyme, causing the accumulation of abnormal short-chain
      glycogen in liver, blood cells, myocardium and striated muscle. Symptoms improve
      after puberty but the increased metabolism of pregnancy predisposes to
      hypoglycaemia, ketosis and lactic acidosis. Cardiomyopathy, distal weakness and
      peripheral neuropathy may present after the third decade. The patient was managed
      antenatally with regular cornflour feeds and was scheduled for elective caesarean
      delivery. She presented in early labour at 38 weeks and delivered a healthy
      neonate by urgent caesarean delivery under spinal anaesthesia. Intravenous
      dextrose infusion and regular blood glucose monitoring were used during the
      perinatal period to prevent hypoglycaemia. An arterial line was inserted in the
      operating room for frequent blood sampling and to avoid muscle cramps which could
      be induced by the intermittent inflation of the automated blood pressure cuff.
      Obstetric, anaesthetic and neonatal outcomes were uneventful.

PMID- 22138525
TI  - Type A aortic dissection in pregnancy.
AB  - Type A aortic dissection is a life-threatening event to both mother and baby, and
      accounted for 14% of maternal cardiac deaths in the 2006-2008 UK Confidential
      Enquiries into Maternal Deaths. Difficulty exists in the diagnosis of this rare
      but potentially curable condition, the mortality of which increases with delay in
      diagnosis. We present a case of acute type A aortic dissection in a previously
      well multiparous woman, treated successfully by aortic root repair immediately
      following caesarean section. The acute presentation of aortic dissection and
      diagnostic clues that may have expedited the diagnosis are discussed. A brief
      literature review is presented of the perioperative management of patients
      undergoing cardiothoracic surgery post-caesarean section and the modifications to
      standard techniques that are required.

PMID- 22138527
TI  - Bibliography. Vasculitis syndromes. Current world literature.

PMID- 22138526
TI  - Peripartum management of two parturients with ornithine transcarbamylase
      deficiency.
AB  - Ornithine transcarbamylase deficiency is a rare X-linked disorder in which female
      carriers are usually heterozygous for the ornithine transcarbamylase deficiency
      gene. In pregnancy it has been associated with altered mental status, seizures,
      coma and death, especially in the postpartum period. We report the management of
      labor and delivery in two parturients with known ornithine transcarbamylase
      deficiency. Both patients were maintained on arginine, citrulline and sodium
      phenylacetate therapy with restricted protein intake during pregnancy. Neuraxial
      techniques were used for pain relief in labor and anesthesia for operative
      delivery. A dextrose infusion provided caloric intake during labor and
      perioperatively.

PMID- 22138529
TI  - Binocular fusion of luminance, color, motion and flicker--two eyes are worse than
      one.
AB  - How much information is conserved, or discarded, as it travels through the visual
      system? A target (an oriented bar) was defined by dark grey spots embedded in
      light spots for the left eye, and by light grey spots embedded in dark spots for
      the right eye. With one eye open, the target bars were clearly visible, but with
      both eyes open the light and dark spots fused binocularly into medium grey and
      the target vanished. Results were similar for color; the target comprised
      greenish spots embedded in reddish spots for the left eye, and by reddish spots
      embedded in greenish spots for the right eye (somewhat like an Isihara color
      plate). RESULT: The colored targets were invisible when both eyes were open but
      reappeared when one eye was closed. Small targets that moved in opposite
      directions in the two eyes were visible to each eye alone by common fate, but
      motion averaging made them disappear when both eyes were open. CONCLUSION:
      Opposed retinal luminances or colors were averaged out by binocular fusion, but
      could be retrieved by a special afterimage technique in Experiment 6. Conversely,
      in Experiment 7 dichoptic target spots flickered in counterphase but background
      spots flickered in-phase to the two eyes. RESULT: The targets were invisible
      monocularly but became visible as reduced-flicker when fused binocularly. We
      conclude that two eyes were worse than one eye when opposite colors or movements
      were fused (Experiments 1-6) but were better than one when binocular correlations
      could be extracted (Experiment 7). These experiments show how much of the visual
      information gets transmitted, gets discarded, can still be retrieved, or reaches
      conscious awareness.

PMID- 22138530
TI  - Variability in constancy of the perceived surface reflectance across different
      illumination statistics.
AB  - In contrast to the classical findings of lightness constancy, recent
      psychophysical studies show the strong dependency of the perceived reflectance of
      a surface on the structure of the natural illumination. The present study
      examined this inconstancy for systematic variations in the light field and an
      image-based explanation for it. Observers matched the specular and diffuse
      reflectance of a three-dimensional object in a complex scene under a fixed light
      field to that in the scene under different light fields with variable mean,
      contrast, and gamma. For the both specular and diffuse components, the matched
      reflectance was relatively constant against changes in the mean illuminance but
      varied extensively with changes in the contrast and gamma of the light field. We
      found that the matching data were well predicted by the similarity of the subband
      histograms of the images. The results support the notion that early spatial
      filtering can provide a unified account of both the constancy in the perceived
      surface reflectance against mean illuminance and the inconstancy for higher-order
      illumination statistics.

PMID- 22138531
TI  - Askin tumor: four case reports and a review of the literature.
AB  - Askin tumor is an uncommon malignant neoplasm in the thoracopulmonary region
      mainly occurring in children and adolescents. Four young patients with
      histologically proven Askin tumors were treated in our hospital. In all patients,
      chest computed tomography imaging demonstrated a chest wall mass with or without
      destruction of ribs. All patients underwent radical mass resection and
      postoperative chemotherapy. By the time this article was completed, two of the
      patients had died with local chest wall recurrences. Here we focus on the imaging
      features, differential diagnosis, pathology and prognosis of this rare disease.

PMID- 22138532
TI  - Arthroscopic De Novo NT((r)) juvenile allograft cartilage implantation in the
      talus: a case presentation.
AB  - Osteochondral defects of the talus are a challenging subject facing foot and
      ankle surgeons. The available treatment options have relatively good subjective
      outcomes; however, they are limited by the ability to reproduce hyaline
      cartilage, the need for multiple surgeries, and high morbidity. We present a new
      technique using DeNovo NT((r)) juvenile allograft cartilage implantation
      introduced into a talar lesion arthroscopically in a single procedure to repair a
      posteriomedial talar osteochondral defects in a healthy, active 30-year-old
      female. The patient tolerated the procedure well. At the 6-month follow-up visit,
      the patient had returned to full activity, and at 24 months, she remained
      completely pain free.

PMID- 22138533
TI  - Entopic overexpression of Ascl2 does not accelerate tumourigenesis in ApcMin
      mice.
AB  - OBJECTIVE: Expression of the Wnt target gene ASCL2 is elevated in 78% of
      intestinal neoplasia datasets (Oncomine), suggesting a role for deregulated ASCL2
      in the aetiology of intestinal tumourigenesis. Furthermore, ectopic expression of
      Ascl2 has previously been shown to lead to hyperplasia in the mouse. However,
      elevated levels of ASCL2 does not have an impact on the overall survival or
      recurrence-free survival rates in colorectal cancer patients. Here the authors
      use a novel mouse model to analyse the role of Ascl2 in intestinal tumourigenesis
      and address the controversy surrounding the relevance of this gene to the
      aetiology of colorectal cancer. DESIGN: The authors have generated a mouse
      possessing a transgene carrying the Ascl2 gene together with its endogenous
      promoter and regulatory regions, thereby elevating Ascl2 expression in an
      authentic manner. The authors have further intercrossed these Ascl2
      overexpressers to the classic Apc(Min)   model, to study the consequence of
      elevated Ascl2 expression in intestinal tumourigenesis. RESULTS: Here the authors
      genetically demonstrate that elevated expression of Ascl2 in a Wnt signalling
      dependent manner specifically in the stem cell compartment of the intestine
      neither increases tumour formation nor diminishes survival in a well established
      intestinal tumour model, the Apc(min)   mouse. CONCLUSION: The authors conclude
      that ectopic expression of Ascl2 is more important in the aetiology of neoplasia
      than overexpression of Ascl2.

PMID- 22138534
TI  - Fourier analysis of arterial pulse in patients with advanced cirrhosis indicates
      reduced wave reflections that may protect against manifest cardiac dysfunction.

PMID- 22138535
TI  - The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising
      enterocolitis in neonatal rats.
AB  - BACKGROUND: Necrotising enterocolitis (NEC) is one of the most common and fatal
      intestinal disorders in preterm infants. Breast-fed infants are at lower risk for
      NEC than formula-fed infants, but the protective components in human milk have
      not been identified. In contrast to formula, human milk contains high amounts of
      complex glycans. OBJECTIVE: To test the hypothesis that human milk
      oligosaccharides (HMO) contribute to the protection from NEC. METHODS: Since
      human intervention studies are unfeasible due to limited availability of HMO, a
      neonatal rat NEC model was used. Pups were orally gavaged with formula without
      and with HMO and exposed to hypoxia episodes. Ileum sections were scored blindly
      for signs of NEC. Two-dimensional chromatography was used to determine the most
      effective HMO, and sequential exoglycosidase digestions and linkage analysis was
      used to determine its structure. RESULTS: Compared to formula alone, pooled HMO
      significantly improved 96-hour survival from 73.1% to 95.0% and reduced pathology
      scores from 1.98 +/- 1.11 to 0.44 +/- 0.30 (p<0.001). Within the pooled HMO, a
      specific isomer of disialyllacto-N-tetraose (DSLNT) was identified to be
      protective. Galacto-oligosaccharides, currently added to formula to mimic some of
      the effects of HMO, had no effect. CONCLUSION: HMO reduce NEC in neonatal rats
      and the effects are highly structure specific. If these results translate to NEC
      in humans, DSLNT could be used to prevent or treat NEC in formula-fed infants,
      and its concentration in the mother's milk could serve as a biomarker to identify
      breast-fed infants at risk of developing this disorder.

PMID- 22138536
TI  - A splicing variant leads to complete loss of function of betaine-homocysteine
      methyltransferase (BHMT) gene in hepatocellular carcinoma.
AB  - The remethylation of homocyteine into methionine is catalyzed either by
      methionine synthase (MTR) or by betaine-homocysteine methyltransferase (BHMT), in
      the liver. Choline/betaine deficiency and impaired BHMT pathway have been
      associated with hepatocellular carcinogenesis, in animal models. The molecular
      mechanisms that impair the BHMT pathway are unknown. We aimed to investigate
      BHMT, BHMT2, and MTR expression in HepG2 cells and human hepatocarcinoma tissues.
      Transcripts were quantified by RT-qPCR and splicing was assessed by analysis of
      exon junctions and sequencing of variants. Protein expression was studied by
      Western Blot, immunohistochemistry and enzyme activity. Tumor tissue was compared
      with surrounding healthy tissue. RT-qPCR of HepG2 cells and of tumor samples
      showed a strong decrease of transcripts of BHMT and BHMT2, compared to normal.
      MTR transcript levels were not different. The decreased BHMT expression resulted
      from the transcription of a splicing variant that produced a frameshift in exon
      4, with a premature termination codon in exon 5 and a loss of function of the
      gene. This splicing variant did not fit with any mechanism resulting from known
      splicing consensus sequences and was not detected in normal adult and fetal
      liver. Consistently, BHMT activity was abolished in HepG2 and protein expression
      was not detectable in HepG2 and in 5 of the 6 tumor samples, compared to normal
      tissues. In conclusion, a transcription variant of exon 4 produces a loss of
      function of BHMT in human hepatocarcinoma. Whether this abnormal transcription of
      BHMT is part or consequence of liver carcinogenesis should deserve further
      investigations.

PMID- 22138537
TI  - Measurement of gender-sensitive treatment for women in mixed-gender substance
      abuse treatment programs.
AB  - BACKGROUND: Gender-sensitive (GS) substance abuse treatment services have emerged
      in response to the multidimensional profile of problems that women display upon
      admission to substance abuse treatment. The present study examines the extent to
      which treatment programs vary in GS programming for women in real-world mixed
      gender treatment settings, where most women are treated. METHODS: Data were
      collected through site visits using semi-structured interviews with program
      directors, clinical directors, and counselors in 13 mixed-gender treatment
      programs from Washington State. Rasch modeling techniques were used to analyze
      the data. RESULTS: Naturally occurring variation was revealed within and across
      the treatment programs, and demonstrated that reliable measures of three GS
      domains (Grella, 2008) can be constructed despite a small number of programs.
      CONCLUSIONS: This is the first study to quantify GS treatment for substance
      abusing women. The identified treatment services and practices and the way they
      clustered together to form scales have practical implications for researchers,
      service providers, clinicians, and policy makers. The scales can be used to study
      treatment outcomes and to evaluate the effectiveness, cost-effectiveness, and
      cost-benefit of GS programming for women.

PMID- 22138538
TI  - Non-injection drug use and hepatitis C among drug treatment clients in west
      central Mexico.
AB  - BACKGROUND: Research on hepatitis C virus (HCV) prevalence among non-injecting
      drug treatment clients in the United States, Europe and Asia indicate substantial
      differences by place. To date, little or no research on HCV and non-injection
      drug use (NIDU) has been conducted in Mexico. METHODS: We examined the prevalence
      of HCV, hepatitis B virus (HBV), and HIV among non-injecting drug users (NIDUs)
      in community-based drug treatment (N=122) and NIDUs in a prison-based drug
      treatment program (N=30), both located in west central Mexico. RESULTS: Among the
      community clients, prevalence was 4.1% (95% confidence interval [CI]: 1.8-9.2)
      for HCV, 5.7% for HBV (95% CI: 2.8-11.4), and 1.6% for HIV (95% CI: 0.4-5.8).
      Among the in-prison clients, prevalence was 40.0% (95% CI: 24.6-57.7) for HCV,
      20.0% for HBV (95% CI: 9.5-37.3), and 6.7% for HIV (95% CI: 1.9-21.3). None of
      the clients were aware of being infected. CONCLUSION: The HCV prevalence found
      for the NIDU community treatment clients ranks among the lower HCV estimates
      published for NIDUs in treatment to date. The prevalence found for the in-prison
      clients ranks among the higher, raising a concern of possible elevated HCV
      infection among NIDUs in the west central Mexico prison--one compounded by the
      finding that none of this study's clients knew they were HCV positive.

PMID- 22138539
TI  - Associations between energy drink consumption and alcohol use behaviors among
      college students.
AB  - BACKGROUND: To explore associations between energy drink consumption and alcohol
      use among college students. METHODS: Participants included 585 students (m
      age=18.7; 47.0% White, 21% Hispanic, 25% Asian, 7% other race/ethnicity; 56.0%
      female). Energy drink behaviors included past month and past week consumption.
      Alcohol use behaviors included past month and past two week consumption, as well
      as heavy drinking and quantity of alcohol consumed. Consumption of energy drinks
      mixed with alcohol was also measured. Linear and logistic regression analyses
      between energy drink consumption and alcohol use were run controlling for gender,
      age, and race/ethnicity. RESULTS: For each one unit increase in past month (i.e.,
      additional day used) energy drink use, the likelihood of past month alcohol use
      increased by 80%, heavy drinking by 80% and past month energy drinks mixed with
      alcohol use by 90%. Similar results were found for past week energy drink use. A
      positive relationship between energy drink use and quantity of alcohol consumed
      during a single episode of drinking was also found (p<0.001). Significant gender
      interactions between energy drink consumption and alcohol use as well as quantity
      of alcohol consumed were found, with relationships stronger among males than
      females. There were no significant interactions by race/ethnicity. CONCLUSIONS:
      Energy drinks are readily available to students and pose potential health risks.
      Students who report greater energy drink consumption also consume more alcohol,
      are more likely to mix energy drinks and alcohol, and experience heavy episodes
      of drinking, which is problematic given the potential negative consequences of
      these drinks.

PMID- 22138540
TI  - Understanding the trends in HIV and hepatitis C prevalence amongst injecting drug
      users in different settings--implications for intervention impact.
AB  - BACKGROUND: A recent systematic review observed that HIV prevalence amongst
      injectors is negligible (<1%) below a threshold HCV prevalence of 30%, but
      thereafter increases with HCV prevalence. We explore whether a model can
      reproduce these trends, what determines different epidemiological profiles and
      how this affects intervention impact. METHODS: An HIV/HCV transmission model was
      developed. Univariate sensitivity analyses determined whether the model projected
      a HCV prevalence threshold below which HIV is negligible, and how different
      behavioural and epidemiological factors affect the threshold. Multivariate
      uncertainty analyses considered whether the model could reproduce the observed
      breadth of HIV/HCV epidemics, how specific behavioural patterns produce different
      epidemic profiles, and how this affects an intervention's impact (reduces
      injecting risk by 30%). RESULTS: The model projected a HCV prevalence threshold,
      which varied depending on the heterogeneity in risk, mixing, and injecting
      duration in a setting. Multivariate uncertainty analyses showed the model could
      produce the same range of observed HIV/HCV epidemics. Variability in injecting
      transmission risk, degree of heterogeneity and injecting duration mainly
      determined different epidemic profiles. The intervention resulted in 50%/28%
      reduction in HIV incidence/prevalence and 37%/10% reduction in HCV
      incidence/prevalence over five years. For either infection, greater impact
      occurred in settings with lower prevalence of that infection and higher
      prevalence of the other infection. DISCUSSION: There are threshold levels of HCV
      prevalence below which HIV risk is negligible but these thresholds are likely to
      vary by setting. A setting's HIV and HCV prevalence may give insights into IDU
      risk behaviour and intervention impact.

PMID- 22138542
TI  - Changes in the expression of apoptosis-related proteins in the life cycle of
      human villous trophoblast.
AB  - The outer layer of the human placenta is the multinucleated syncytiotrophoblast.
      The syncytiotrophoblast is formed by the fusion of mononuclear cytotrophoblasts,
      and aged syncytiotrophoblast nuclei are extruded into the maternal blood as
      membrane-enclosed "syncytial nuclear aggregates" that are then eliminated from
      the maternal circulation. Apoptosis proteins are hypothesized to be involved in
      both of these processes, but the mechanism of death in the syncytiotrophoblast is
      unclear and death processes in this multinucleated layer are likely to differ
      from related processes in mononuclear cells. We have used a combination of
      villous explant culture and immunohistochemical staining of semi-serial sections
      from the explants to study the changing expression of 4 proteins that are markers
      of apoptotic processes in first-trimester human placentae. These studies show
      that Bcl-2 expression is limited to the syncytiotrophoblast and syncytial nuclear
      aggregates, while conversely Bax is expressed in some cytotrophoblasts. Activated
      caspase 3 and the M30 cytokeratin neoepitope were localized to isolated regions
      of the syncytiotrophoblast and some syncytial nuclear aggregates but were never
      present in the same area. Combining our results with those of others, we suggest
      a refined scheme whereby proteins of the apoptosis cascade participate in both
      the processes of syncytial formation and death.

PMID- 22138541
TI  - Nuclear receptor, coregulator signaling, and chromatin remodeling pathways
      suggest involvement of the epigenome in the steroid hormone response of
      endometrium and abnormalities in endometriosis.
AB  - Human endometrium, a steroid hormone-dependent tissue, displays complex cellular
      regulation mediated by nuclear receptors (NRs). The NRs interact with histone
      modifying and DNA-methylating/-demethylating enzymes in the transcriptional
      complex. We investigated NRs, their coregulators, and associated signaling
      pathways in endometrium across the normal menstrual cycle and in endometriosis,
      an estrogen-dependent, progesterone-resistant disorder. Endometrial tissue was
      processed for analysis of 84 genes using NR and coregulator polymerase chain
      reaction (PCR) arrays. Select genes were validated by immunohistochemistry.
      Ingenuity pathway analysis identified DNA methylation and transcriptional
      repression signaling as the most affected pathway in endometrium in women with
      versus without endometriosis, regardless of cycle phase. Thyroid hormone receptor
      (THR) and vitamin D receptor (VDR) pathways were also regulated in normal and
      disease endometrium by activation of TH or vitamin D regulated genes. These data
      support the involvement of the epigenome in steroid hormone response of normal
      endometrium throughout the cycle and abnormalities in endometrium in women with
      endometriosis.

PMID- 22138543
TI  - Dystroglycan expression in human placenta: basement membrane localization and
      subunit distribution change between the first and third trimester.
AB  - OBJECTIVES: This study describes the distribution of dystroglycan (DG) in human
      placenta, membranes, and uterine decidua. STUDY DESIGN: Dystroglycan expression
      was characterized by Western blotting, immunohistochemistry, and
      immunofluorescence microscopy using human tissues and cultured cells. RESULTS:
      Both alpha-DG and beta-DG are expressed in the term syncytiotrophoblast, and
      alpha-DG is localized to the basement membrane. In first-trimester chorionic
      villi, alpha-DG and beta-DG are localized to the periphery of the
      cytotrophoblast. Expression varies in term fetal membranes. alpha-Dystroglycan is
      not detectable in choriocarcinoma cells or HTR cells, but beta-DG is present in
      both normal and cleaved forms. CONCLUSION: Dystroglycan is expressed at high
      levels in human trophoblasts, and localization of the alpha- and beta-subunits
      varies with gestational age and trophoblast differentiation. Because DG
      expression inversely correlates with invasiveness in many cancers, its pattern of
      expression in trophoblasts suggests a possible function in inhibition of
      placental invasion.

PMID- 22138544
TI  - MTHFR C677T polymorphism and recurrent early pregnancy loss risk in north Indian
      population.
AB  - Recurrent early pregnancy loss (REPL) is a multifactorial disorder as both
      genetic and environmental factors contribute to the development of disease.
      Folate metabolism is an important mechanism to ensure proper fetal growth.
      Hyperhomocysteinemia leads to a number of disorders and REPL is one of them. In a
      case-control study DNA from 106 cases with the history of 3 or more REPL and 140
      healthy fertile controls with successful pregnancy outcomes were genotyped for
      C677T single-nucleotide polymorphism (SNP) of the MTHFR
      (methylenetetrahydrofolate reductase) gene through polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP), which was further confirmed
      by sequencing. Allele frequencies of REPL cases were compared with healthy
      controls and a statistically significant association was found between REPL and
      the mutant T allele (chi2 = 8.786, odds ratio [OR] = 2.20, 95% confidence
      interval [CI] = 1.323-3.9658, P = .003). The genotype frequencies of SNP C677T
      also differ significantly between these 2 groups (chi2 = 8.237, P = .016). The OR
      for heterozygous CT in the REPL versus controls is 1.9591 (95% CI = 1.0285
      3.7318, P = .04). The OR for TT homozygous is 6.3009 (95% CI = 1.2065, P = .02).
      Combined odds ratio of CT and TT against the control has been calculated as
      2.2194 (95% CI = 1.2029-4.0952, P = .02) which is also significant. Thus the
      present study clearly indicates that homozygosity and heterozygosity for the
      MTHFR C677T polymorphism confer a 6.3009- and 1.9591-fold increased risk of
      idiopathic REPL, respectively.

PMID- 22138545
TI  - Postnatal development of metabolic flexibility and enhanced oxidative capacity
      after prenatal undernutrition.
AB  - Metabolic flexibility is the body's ability to adapt to changing energy demand
      and nutrient supply. Maternal undernutrition causes growth restriction at birth
      and subsequent obesity development. Intriguingly, metabolic flexibility is
      maintained due to adaptations of muscle tissue. The aim of the present study was
      to investigate developmental pathways of these adaptive changes. Wistar rats
      received standard chow at either ad libitum (AD) or 30% of ad libitum intake (UN)
      throughout pregnancy. At all ages, metabolic status indicated similar insulin
      sensitivity in AD and UN offspring despite the development of adiposity in UN
      offspring at weaning. Type IIA fiber size was reduced in soleus muscle of UN
      offspring at weaning and they had a higher percentage of type I fibers in
      adulthood with a concomitantly higher oxidative capacity. Plasticity of muscle
      was present during the postnatal period and proposes novel pathways for the
      dynamic development of metabolic flexibility throughout postnatal life.

PMID- 22138547
TI  - Immunology of uterine transplantation: a review.
AB  - The idea of using organ transplantation to solve quality-of-life issues was first
      introduced a century ago, with cornea transplants and thrusted before the world
      again in 1998, following a controversial hand transplant. Uterus transplantation
      (UTn) has been proposed as another quality-of-life transplant for the cure of
      permanent uterine factor infertility. In order to proceed in humans, a greater
      appreciation of the immunological mechanisms that underlie UTn is desirable.
      Allogeneic UTn (animal model) was first described by 2 studies in 1969. The first
      and only human UTn, performed in 2000, was an early attempt with limited use of
      animal model experiments prior to moving onto the human setting. Since then, work
      using rat, mouse, ovine, goat, and nonhuman primate models has demonstrated that
      the uterus is a very different but manageable organ immunologically compared to
      other transplanted organs. Therefore, specifically exploring immunological issues
      relating to UTn is a valuable and necessary part of the inevitable scientific
      process leading to successful human UTn.

PMID- 22138546
TI  - Metabolism of 17-alpha-hydroxyprogesterone caproate by human placental
      mitochondria.
AB  - Perfusion of 17-alpha-hydroxyprogesterone caproate (17HPC) via the maternal
      circuit of a dually perfused human placental lobule resulted in the extensive
      formation of 2 metabolites. On the other hand, human placental microsomes
      biotransformed 17HPC into 5 monohydroxylated metabolites, which did not
      correspond to those formed during perfusion. The goal of this investigation was
      to determine the subcellular localization of the enzymes responsible for the
      biotransformation of 17HPC during its perfusion in human placenta. Crude
      subcellular fractions of the human placental tissue were utilized. Six 17HPC
      metabolites were formed by the placental mitochondrial fraction, of which 4 were
      identical to those formed by the microsomes; whereas the other 2, namely MM and
      M19, were formed by the mitochondrial fraction only. The latter metabolites were
      identical to those formed during 17HPC perfusion, as determined by liquid
      chromatography-mass spectrometry (LC-MS) analysis. Therefore, these data strongly
      suggest that the enzymes responsible for the biotransformation of 17HPC during
      its perfusion are predominantly localized in human placental mitochondria.

PMID- 22138548
TI  - Lactoferricin B inhibits the phosphorylation of the two-component system response
      regulators BasR and CreB.
AB  - Natural antimicrobial peptides provide fundamental protection for multicellular
      organisms from microbes, such as Lactoferricin B (Lfcin B). Many studies have
      shown that Lfcin B penetrates the cell membrane and has intracellular activities.
      To elucidate the intracellular behavior of Lfcin B, we first used Escherichia
      coli K12 proteome chips to identify the intracellular targets of Lfcin B. The
      results showed that Lfcin B binds to two response regulators, BasR and CreB, of
      the two-component system. For further analysis, we conducted several in vitro and
      in vivo experiments and utilized bioinformatics methods. The electrophoretic
      mobility shift assays and kinase assays indicate that Lfcin B inhibits the
      phosphorylation of the response regulators (BasR and CreB) and their cognate
      sensor kinases (BasS and CreC). Antibacterial assays showed that Lfcin B reduced
      E. coli's tolerance to environmental stimuli, such as excessive ferric ions and
      minimal medium conditions. This is the first study to show that an antimicrobial
      peptide inhibits the growth of bacteria by influencing the phosphorylation of a
      two-component system directly.

PMID- 22138549
TI  - Anti-fungal activity of cold and hot water extracts of spices against fungal
      pathogens of Roselle (Hibiscus sabdariffa) in vitro.
AB  - Crude extracts of seven spices, viz. cardamom, chilli, coriander, onion, garlic,
      ginger, and galangale were made using cold water and hot water extraction and
      they were tested for their anti-fungal effects against the three Roselle
      pathogens i.e. Phoma exigua, Fusarium nygamai and Rhizoctonia solani using the
      'poisoned food technique'. All seven spices studied showed significant anti
      fungal activity at three concentrations (10, 20 and 30% of the crude extract) in
      vitro. The cold water extract of garlic exhibited good anti-fungal activity
      against all three tested fungi. In the case of the hot water extracts, garlic and
      ginger showed the best anti-fungal activity. Of the two extraction methods, cold
      water extraction was generally more effective than hot water extraction in
      controlling the pathogens. Against P. exigua, the 10% cold water extracts of
      galangale, ginger, coriander and cardamom achieved total (100%) inhibition of
      pathogen mycelial growth. Total inhibition of F. nygamai mycelial growth was
      similarly achieved with the 10% cold water extracts garlic. Against R. solani,
      the 10% cold water extract of galangale was effective in imposing 100%
      inhibition. Accordingly, the 10% galangale extract effectively controlled both P.
      exigua and R. solani in vitro. None of the hot water extracts of the spices
      succeeded in achieving 100% inhibition of the pathogen mycelial growth.

PMID- 22138550
TI  - Deletion and overexpression studies on DacB2, a putative low molecular mass
      penicillin binding protein from Mycobacterium tuberculosis H(37)Rv.
AB  - Mycobacterium tuberculosis genome encodes several high and low molecular mass
      penicillin binding proteins. One such low molecular mass protein is DacB2 encoded
      by open reading frame Rv2911 of M. tuberculosis which is predicted to play a role
      in peptidoglycan synthesis. In this study we have tried to gain an insight into
      the role of this accessory cell division protein in mycobacterial physiology by
      performing overexpression and deletion studies. The overproduction of DacB2 in
      non-pathogenic, fast growing mycobacterium Mycobacterium smegmatis mc(2)155
      resulted in reduced growth, an altered colony morphology, a defect in sliding
      motility and biofilm formation. A point mutant of DacB2 was made wherein the
      active site serine residue was mutated to cysteine to abolish the penicillin
      binding function of protein. The overexpression of mutant protein showed similar
      results indicating that the effects produced were independent of protein's
      penicillin binding function. The gene encoding DacB2 was deleted in M.
      tuberculosis by specialized transduction method. The deletion mutant showed
      reduced growth in Sauton's medium under acidic and low oxygen availability. The
      in vitro infection studies with THP-1 cells showed increased intracellular
      survival of dacB2 mutant compared to parent and complemented strains. The colony
      morphology and antibiotic sensitivity of mutant and wild-type strains were
      similar.

PMID- 22138551
TI  - Low-temperature degradation of different zirconia ceramics for dental
      applications.
AB  - The aim of this investigation was to determine the influence of simulated ageing
      on the tetragonal-to-monoclinic phase transformation and on the flexural strength
      of a 3Y-TZP ceramic, compared to alumina toughened zirconia (ATZ) and ceria
      stabilized zirconia (12Ce-TZP). Standardized disc specimens of each material were
      hydrothermally aged in steam at 134 degrees C and 3bar for 0, 16, 32, 64 or 128h.
      The phase transformation was determined by X-ray diffraction (XRD) and atomic
      force microscopy. Scanning electron microscopy was performed to estimate the
      depth of the transformation zone. The flexural strength was investigated in a
      biaxial flexural test. XRD revealed a significant increase in the monoclinic
      phase content for 3Y-TZP and ATZ due to ageing, although this increase was less
      pronounced for ATZ. In contrast, the monoclinic phase content of 12Ce-TZP was not
      influenced. For 3Y-TZP and ATZ, a transformation zone was found of which the
      depth linearly correlated with ageing time, while for 12Ce-TZP no transformation
      zone could be observed. Changes in flexural strength after ageing were
      heterogeneous: while 3Y-TZP showed a significant decrease in strength - from 1740
      to 1169 MPa - with ATZ there was a considerable increase - from 1093 to 1378 MPa.
      The flexural strength of 12Ce-TZP remained unaffected at the low level of about
      500 MPa. These results indicate that both alumina and ceria, as stabilizing
      oxides, reduce the susceptibility of zirconia to hydrothermal degradation; the
      alternative use of these oxides may enhance the clinical long-term stability of
      dental zirconia restorations.

PMID- 22138552
TI  - Behavioral effects of sub-acute inhalation of toluene in adult rats.
AB  - Reports of behavioral effects of repeated inhalation of toluene in rats have
      yielded inconsistent findings. A recent study from this laboratory (Beasley et
      al., 2010) observed that after 13 weeks of inhaled toluene ("subchronic" exposure
      scenario), rats showed mild but persistent changes in behavior, primarily
      involving acquisition of an autoshaped lever-press response. The present
      experiment sought to systematically replicate these findings, using a 4-week "sub
      acute" exposure scenario. Adult male Long-Evans rats inhaled toluene vapor (0,
      10, 100, or 1000 ppm) for 6h/day, 5 days/week for 4 weeks. As in the subchronic
      study, toluene had no effect on motor activity, anxiety-related behavior in the
      elevated plus-maze, or acquisition of the visual discrimination. However, sub
      acute toluene did not affect appetitively-motivated acquisition of the lever
      press response, but did reduce accuracy of signal detection at the end of
      training. Analysis of the deficit in accuracy in the 1000 ppm group by means of
      manipulations of different task parameters suggested a greater influence of
      attentional impairment than visual or motor dysfunction as a source for the
      deficit. These results confirm a pattern of subtle and inconsistent long-term
      effects of repeated daily exposure to concentrations of toluene vapor of 1000 ppm
      and below, in contrast to robust and reliable effects of acute inhalation of the
      solvent at concentrations above 1000 ppm.

PMID- 22138553
TI  - Hepatic safety of efavirenz in HIV/hepatitis C virus-coinfected patients with
      advanced liver fibrosis.
AB  - OBJECTIVE: To assess the frequency of severe liver toxicity in HIV/hepatitis C
      (HCV)-coinfected patients with advanced liver fibrosis receiving efavirenz (EFV)
      based antiretroviral combinations. METHODS: One hundred and eighty-nine
      previously antiretroviral naive, HIV/HCV-coinfected patients, who started a
      regimen including two nucleoside analogues plus EFV, and in whom the presence or
      absence of advanced liver fibrosis could be established, were retrospectively
      analyzed. Liver fibrosis was evaluated according to a stepwise algorithm
      including liver biopsy, transient elastography and FIB-4 index. RESULTS: Fifty
      six patients had advanced fibrosis - 25 with cirrhosis - and 133 did not. Three
      (5.4%) subjects with and 9 (6.8%) (p=0.717) without advanced fibrosis developed
      grade 3-4 transaminase elevation (TE). Grade 4 total bilirubin elevation was seen
      in 5 (8.9%) patients with advanced fibrosis and in 1 (0.8%) without it (p=0.003).
      Liver events led to EFV discontinuation in 10 (5.3%) patients, 6 (10.7%) with and
      4 (3%) without advanced fibrosis (p=0.031). CONCLUSIONS: The hepatic tolerability
      of EFV was good in HIV/HCV-coinfected patients with advanced liver fibrosis. The
      frequency of grade 3-4 TE was similar to that observed in patients without
      advanced fibrosis, there was no death attributable to liver failure caused by
      drug toxicity and the rate of EFV discontinuations due to liver events was low.

PMID- 22138554
TI  - Dengue virus nonstructural protein NS1 binds to prothrombin/thrombin and inhibits
      prothrombin activation.
AB  - OBJECTIVES: Dengue virus (DENV) infection may result in severe dengue hemorrhage
      fever (DHF). However the mechanisms to cause hemorrhage during DENV infection are
      not fully understood. The sera level of secreted DENV nonstructural protein 1
      (NS1) is correlated with the development of DHF. However, whether secreted NS1
      can interfere with coagulation and contribute to the hemorrhage in DHF is
      unknown. Since thrombin plays a very important role in the activation of
      coagulation, we investigated whether NS1 can bind to thrombin and affect its
      formation or activity. METHODS AND RESULTS: We first demonstrated that NS1 could
      bind to thrombin and formed NS1/thrombin complex in dengue patients' sera by
      enzyme-linked immunosorbent assay (ELISA). The ability of NS1 binding to
      prothrombin or thrombin was further confirmed using recombinant NS1 (rNS1) by
      ELISA, co-immunoprecipitation, and rNS1-affinity column purification. Even though
      the binding of rNS1 to thrombin showed no effect on thrombin activity, rNS1 could
      inhibit prothrombin activation and prolong activated partial thromboplastin time
      (APTT) of human platelet poor plasma. CONCLUSION: These results suggest secreted
      DENV NS1 may bind to prothrombin and inhibit it activation, which in turn, may
      contribute to the APTT prolongation and hemorrhage in DHF patients.

PMID- 22138555
TI  - The retina is a target for GnRH-3 system in the European sea bass, Dicentrarchus
      labrax.
AB  - The European sea bass expresses three GnRH (Gonadotrophin Releasing Hormone)
      forms that exert pleiotropic actions via several classes of receptors. The GnRH-1
      form is responsible for the endogenous regulation of gonadotrophin release by the
      pituitary gland but the role of GnRH-2 and GnRH-3 remains unclear in fish. In a
      previous study performed in sea bass, we have provided evidence of direct links
      between the GnRH-2 cells and the pineal organ and demonstrated a functional role
      for GnRH-2 in the modulation of the secretory activity of this photoreceptive
      organ. In this study, we have investigated the possible relationship between the
      GnRH-3 system and the retina in the same species. Thus, using a biotinylated
      dextran-amine tract-tracing method, we reveal the presence of retinopetal cells
      in the terminal nerve of sea bass, a region that also contains GnRH-3
      immunopositive cells. Moreover, GnRH-3-immunoreactive fibers were observed at the
      boundary between the inner nuclear and the inner plexiform layers, and also
      within the ganglion cell layer. These results strongly suggest that the GnRH-3
      neurons located in the terminal nerve area represent the source of GnRH-3
      innervation in the retina of this species. In order to clarify whether the retina
      is a target for GnRH, the expression pattern of GnRH receptors (dlGnRHR) was also
      analyzed by RT-PCR and in situ hybridization. RT-PCR revealed the retinal
      expression of dlGnRHR-II-2b, -1a, -1b and -1c, while in situ hybridization only
      showed positive signals for the receptors dlGnRHR-II-2b and -1a. Finally, double
      immunohistochemistry showed that GnRH-3 projections reaching the sea bass retina
      end in close proximity to tyrosine hydroxylase (dopaminergic) cells, which also
      expressed the dlGnRHR-II-2b receptor subtype. Taken together, these results
      suggest an important role for GnRH-3 in the modulation of dopaminergic cell
      activities and retinal functions in sea bass.

PMID- 22138557
TI  - Roles of alphavbeta5, FAK and MerTK in oxidative stress inhibition of RPE cell
      phagocytosis.
AB  - Efficient phagocytosis of photoreceptor outer segments (POS) by retinal pigment
      epithelial cells (RPE) plays a key role in biological renewal of these highly
      peroxidizable structures and in maintenance of retina health. Here, we used an in
      vitro RPE cell phagocytosis assay to investigate how sub-lethal oxidative stress
      modifies the key components of the cell phagocytic machinery leading to severe
      impairment of phagocytosis. Sub-lethal oxidative treatment, induced by hydrogen
      peroxide (H(2)O(2)), significantly inhibited binding and uptake of POS by RPE
      cells. However, sub-lethal oxidative stress did not affect cell surface
      expression of alphavbeta5 or RPE cell adhesion to alphavbeta5. Similarly, the
      enzymatic activity of mature cathepsin D was not altered upon challenge by
      oxidative stress. In contrast, studies of signaling molecules in the RPE cell
      phagocytic machinery revealed that sub-lethal oxidative stress inhibits POS
      induced activation of FAK and MerTK. Our data demonstrate that sub-lethal
      oxidative treatment with H(2)O(2) inhibits phagocytic activity of ARPE-19 cells,
      in part by inhibiting FAK and MerTK.

PMID- 22138556
TI  - In vitro studies on immunotoxic potential of Orange II in splenocytes.
AB  - Orange II, an azo dye, is not permitted in food preparations, but high levels of
      the dye have been detected in different food commodities. Though there are
      reports on the toxicity of Orange II but knowledge based on the immunomodulatory
      properties of Orange II is scanty. The present investigation was undertaken to
      study the in vitro immunotoxic potential of Orange II in splenocytes. Splenocytes
      were isolated, cultured and subjected to immunophenotypic analysis, mixed
      lymphocyte reaction (MLR) assay or stimulated with lipopolysaccharide (LPS) or
      concanavalin A (Con A) for 72 h. The supernatant was collected for cytokine
      assays. Orange II showed cytotoxic effects at 100-1000MUg/ml concentrations and
      50MUg/ml was determined as the highest non-cytotoxic dose. Orange II at the non
      cytotoxic dose (50MUg/ml) significantly altered the relative distribution of T
      and B-cells, MLR response and the mitogen induced proliferative response of T
      cells and B-cells. Consistent with the hypo-responsiveness of the T and B
      lymphocytes, Orange II induced a concomitant decline in the secretion of
      cytokines IL-2, IL-4, IL-6, IFN-gamma, TNF-alpha and IL-17. On the contrary,
      there was an increase in the production of IL-10, an anti-inflammatory regulatory
      cytokine, which may be one of the causative factor for immunosuppressive property
      of Orange II. These results suggest that non-cytotoxic dose of Orange II may have
      immunomodulatory effects.

PMID- 22138559
TI  - Real neuroscience in virtual worlds.
AB  - Virtual reality (VR) holds great promise as a tool to study the neural circuitry
      underlying animal behaviors. Here, we discuss the advantages of VR and the
      experimental paradigms and technologies that enable closed loop behavioral
      experiments. We review recent results from VR research in genetic model organisms
      where the potential combination of rich behaviors, genetic tools and cutting edge
      neural recording techniques are leading to breakthroughs in our understanding of
      the neural basis of behavior. We also discuss several key issues to consider when
      performing VR experiments and provide an outlook for the future of this exciting
      experimental toolkit.

PMID- 22138558
TI  - Quantitative study of the topographic distribution of conjunctival lymphatic
      vessels in the monkey.
AB  - The purpose of this study was to quantify the topographic distribution of bulbar
      conjunctival microlymphatic vessels in the monkey. Sixteen eyes from 8 rhesus
      monkeys were used. Full thickness pieces of globe wall were excised from each
      quadrant. Cryosections were stained for 5'-nucleotidase, an enzyme histochemical
      staining for lymphatic vessels, or vascular endothelial growth factor receptor-3,
      an immunohistochemical marker for the identification of lymphatic endothelial
      cells, and then counterstained by hematoxylin. The remaining bulbar conjunctiva
      was dissected and flat mounted. The tissue was then processed with 5'
      nucleotidase and alkaline phosphatase, an enzyme histochemical stain with higher
      activity in blood vessels. Microscope images were further analysed by image
      processing. The density of lymphatics, diameter of lymphatic vessels, and the
      size of the drainage zone of each blind end of the initial lymphatics were
      studied. Conjunctival lymphatics consisted of initial lymphatics and pre
      collectors. The initial lymphatics with blind ends were predominately distributed
      just under the epithelium. The density of these lymphatics (~50%) and the
      drainage zone area (~0.81 mm(2)) was similar in each quadrant, with no difference
      in the limbus and fornix regions. The average diameter of lymphatic vessels in
      each quadrant ranged from 82 to 111 MUm, and was greater in the superior and
      nasal regions. Larger calibre pre-collectors with valve-like structures were
      mostly located sub Tenon's membrane and predominantly located in the region mid
      way between the limbus and fornix. There was a marked depth difference in initial
      lymphatic distribution, with the initial lymphatics mostly confined to the region
      between Tenon's membrane and the conjunctival epithelium. Detailed knowledge of
      the topographic distribution of conjunctival lymphatics have significant
      relevance to a better understanding of immunology, drug delivery, glaucoma
      filtration surgery, and tumour metastasis in the conjunctiva.

PMID- 22138560
TI  - Mitochondrial dysfunction in glaucoma: understanding genetic influences.
AB  - Glaucoma is the leading cause of irreversible blindness worldwide. This review
      aims to provide a greater understanding of the complex genetic influences that
      may lead to mitochondrial dysfunction and increase susceptibility to retinal
      ganglion cell (RGC) loss in primary open angle glaucoma (POAG), and thus
      elucidate potentially important pathophysiological pathways amenable to
      therapeutic intervention. Emerging evidence from genome wide association and
      other genetic studies suggests that changes in the mitochondrial DNA (mtDNA) and
      in nuclear DNA genes that encode mitochondrial proteins may influence
      mitochondrial structure and function and, therefore, contribute to the
      pathogenesis of POAG. We propose that a variety of genes (OPA1, MFN1, MFN2,
      CYP1B1, PARL, SOD2, SRBD1, GST, NOS3, TNFa and TP53) may each confer a background
      susceptibility to POAG in different populations having one common link:
      mitochondrial dysfunction. The relationship between polymorphisms in these genes
      and increasing risk for POAG is presented and the limitations of the available
      current knowledge are discussed.

PMID- 22138561
TI  - Reduced levels of active GLP-1 in patients with cystic fibrosis with and without
      diabetes mellitus.
AB  - Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive
      peptide from intestinal L-cells in response to eating. It acts on target cells
      and exerts several functions as stimulating insulin and inhibiting glucagon. It
      is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as
      an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs
      in patients with type 2 diabetes. We served patients with cystic fibrosis (CF,
      n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18)
      a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an
      overnight fasting. Blood samples were collected before meal as well as 15, 30, 45
      and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of
      the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy
      controls. We found that active GLP-1 was significantly decreased in patients with
      CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients
      with CFRD tended to be lower but were not significantly lower than in patients
      with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups,
      which points to that the inactive form of GLP-1 is more pronounced in CF
      patients. The endogenous insulin production (measured by C-peptide) was
      significantly lower in patients with CFRD as expected. However, levels in non
      diabetic CF patients did not differ from the controls. We suggest that the
      decreased levels of GLP-1 could affect the progression toward CFRD and that more
      studies need to be performed in order to evaluate a possible treatment with GLP-1
      analogues in CF-patients.

PMID- 22138563
TI  - Bridging solubility between drug discovery and development.
AB  - Solubility has a crucial role in the success of a drug candidate. Compounds with
      low solubility not only cause problems for in vitro and in vivo assays, but also
      add significant burdens to drug development. Drug discovery and drug development
      often have different solubility screening requirements and methodologies have
      been developed to meet the needs of these different stages.

PMID- 22138564
TI  - Magnetic resonance enterography findings of chronic radiation enteritis.
AB  - The diagnosis of chronic radiation enteritis (CRE) is considerably challenging
      both for clinicians and radiologists. The aim of this study was to evaluate the
      role of magnetic resonance enterography (MRE) in the diagnosis of CRE. To the
      best of our knowledge, there are no reports on the role of MRE in the diagnosis
      of CRE specifically. In this report, we present MRE findings of 4 patients with
      CRE. The most important factors in CRE diagnosis are the clinical findings and
      medical history, but focal abnormal bowel loop in the region of a known radiation
      field is the most important information. This abnormal loop is generally located
      in the distal ileum as present in our patients. Other associated findings helpful
      for the diagnosis are small bowel thickening, contrast material enhancement in a
      long segment, mesenteric stranding and luminal narrowing. MRE can be sufficient
      and useful in the diagnosis of CRE and for treatment planning, especially in
      patients with significant comorbidities who have had radiotherapy in the past.
      Adding MRE into the diagnostic algorithm can be helpful in post-radiotherapy
      patients with acute/subacute gastrointestinal symptoms.

PMID- 22138562
TI  - Influence of oral lactoferrin on Mycobacterium tuberculosis induced
      immunopathology.
AB  - The ability of lactoferrin to provide protection and decrease immunopathology in
      infectious diseases was evaluated using an aggressive aerosol model of
      Mycobacterium tuberculosis (MTB) infection. C57BL/6 mice were challenged with MTB
      strain Erdman and treated with 0.5% bovine lactoferrin added to the drinking
      water starting at day 0 or day 7 post-infection. Mice were sacrificed at three
      weeks post-challenge and evaluated for organ bacterial burden, lung
      histopathology, and ELISpot analysis of the lung and spleen for immune cell
      phenotypes. Mice given tap water alone had lung log10 colony forming units (CFUs)
      of 7.5 +/- 0.3 at week 3 post-infection. Lung CFUs were significantly decreased
      in mice given lactoferrin starting the day of infection (6.4 +/- 0.7), as well as
      in mice started therapeutically on lactoferrin at day 7 after established
      infection (6.5 +/- 0.4). Quantitative immunohistochemistry using multispectral
      imaging demonstrated that lung inflammation was significantly reduced in both
      groups of lactoferrin treated mice, with decreased foamy macrophages, increased
      total lymphocytes, and increased numbers of CD4+ and CD8+ cells. ELISpot analysis
      showed that lactoferrin treated mice had increased numbers of CD4 + IFN-gamma+
      and IL-17 producing cells in the lung, cells that have protective functions
      during MTB infection. Lactoferrin alone did not alter the proliferation of MTB in
      either broth or macrophage culture, but enhanced IFN-gamma mediated MTB killing
      by macrophages in a nitric oxide dependent manner. These studies indicate that
      lactoferrin may be a novel therapeutic for the treatment of tuberculosis, and may
      be useful in infectious diseases to reduced immune-mediated tissue damage.

PMID- 22138565
TI  - A GFP-actin reporter line to explore microfilament dynamics across the malaria
      parasite lifecycle.
AB  - Malaria parasite motility relies on an internal parasite actomyosin motor that,
      when linked to the host cell substrate, propels motile zoites forward. Despite
      their key role in this process, attempts to visualize actin microfilaments (F
      actin) during motility and under native microscopy conditions have not to date
      been successful. Towards facilitating their visualization we present here a
      Plasmodium berghei transgenic line in which a green fluorescent protein (GFP)
      actin fusion is constitutively expressed through the lifecycle. Focused
      investigation of the largest motile form, the insect stage ookinete, demonstrates
      a large cytosolic pool of actin with no obvious F-actin structures. However,
      following treatment with the actin filament-stabilizing drug Jasplakinolide, we
      show evidence for concentration of F-actin dynamics in the parasite pellicle and
      at polar apices. These observations support current models for gliding motility
      and establish a cellular tool for further exploration of the diverse roles actin
      is thought to play throughout parasite development.

PMID- 22138567
TI  - Aluminum maltolate induces primary rat astrocyte apoptosis via overactivation of
      the class III PI3K/Beclin 1-dependent autophagy signal.
AB  - Aluminum-induced neuronal cell apoptosis has been implicated in various
      neurodegenerative disorders. However, whether autophagy, a vital lysosomal
      degradation pathway, is involved in this pathogenesis still remains unknown. Our
      present findings demonstrated that aluminum significantly increased rat astrocyte
      apoptosis and autophagy levels in a dose-dependent manner. Examination of the
      associated mechanisms revealed that aluminum at low levels (400MUM) did not
      increase apoptosis protein expressions (cleaved caspase-3 and cleaved PARP), but
      markedly up-regulated autophagy-related protein Beclin 1 expression. This
      indicates that the autophagy process occurs earlier than neuronal apoptosis.
      Moreover, aluminum at high levels (1600MUM) significantly induced autophagy
      related protein (Beclin 1 and LC3II) and apoptosis-related protein expressions,
      showing that both autophagy and apoptosis processes are activated under high
      levels of aluminum exposure. We used 3-methyladenine, an inhibitor of class III
      phosphatidylinositol-3 kinase, to treat astrocytes and found that the apoptosis
      rate in the 3-MA/aluminum co-treated group was markedly down-regulated compared
      with aluminum alone-treated astrocytes. The apoptosis protein and autophagy
      related protein expressions were also decreased. These observations showed that
      the mild autophagy process may precede apoptosis in low dose aluminum-insulted
      astrocytes, and high dose aluminum-induced serious autophagy may result in cell
      apoptosis via the Beclin 1-dependent autophagy signal pathway.

PMID- 22138566
TI  - Comet assay analysis of DNA damage in T- and B-lymphocytes separated by MACS for
      human biomonitoring studies.
AB  - In this study, we developed and tested a method for human biomonitoring using
      Comet assays with human T- and B-lymphocytes obtained by magnetic cell sorting
      (MACS). We evaluated DNA damage induced by treatment with hydrogen peroxide
      (H(2)O(2); 5, 25 and 50MUM) and methyl methane sulfonate (MMS; 5, 25 and 50MUM)
      in both human B- and T-lymphocytes obtained by MACS, and compared their DNA
      damage levels. Significant, dose-dependent levels of DNA damage were found in T
      lymphocytes and B-lymphocytes. Furthermore, the level of DNA damage was
      significantly greater in B-lymphocytes than in T-lymphocytes, suggesting that
      human B-lymphocytes may be a more sensitive target than T-lymphocytes for the
      evaluation of DNA damage. In addition, we compared these in vitro exposure data
      with previous studies that showed DNA damage in B- and T-lymphocyte and
      granulocytes of control subjects and industrial workers exposed in vivo to
      environmental toxicants. The use of single types of human peripheral blood
      mononuclear cells obtained by MACS, for Comet assays gave sensitive and reliable
      data for human biomonitoring for environmental toxicants.

PMID- 22138568
TI  - Dietary carotenoid lutein protects against DNA damage and alterations of the
      redox status induced by cisplatin in human derived HepG2 cells.
AB  - Several epidemiological and experimental studies has been reported that lutein
      (LT) presents antioxidant properties. Aim of the present study was to investigate
      the protective effects of LT against oxidative stress and DNA damage induced by
      cisplatin (cDDP) in a human derived liver cell line (HepG2). Cell viability and
      DNA-damage was monitored by MTT and comet assays. Moreover, different biochemical
      parameters related to redox status (glutathione, cytochrome-c and intracellular
      ROS) were also evaluated. A clear DNA-damage was seen with cDDP (1.0MUM)
      treatment. In combination with the carotenoid, reduction of DNA damage was
      observed after pre- and simultaneous treatment of the cells, but not when the
      carotenoid was added to the cells after the exposure to cDDP. Exposure of the
      cells to cDDP also caused significant changes of all biochemical parameters and
      in co-treatment of the cells with LT, the carotenoid reverted these alterations.
      The results indicate that cDDP induces pronounced oxidative stress in HepG2 cells
      that is related to DNA damage and that the supplementation with the antioxidant
      LT may protect these adverse effects caused by the exposure of the cells to
      platinum compound, which can be a good predict for chemoprevention.

PMID- 22138569
TI  - Differential involvement of mitochondrial dysfunction, cytochrome P450 activity,
      and active transport in the toxicity of structurally related NSAIDs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment
      of pain and inflammation. However, this group of drugs is associated with serious
      adverse drug reactions. Previously, we studied the mechanisms underlying toxicity
      of the NSAID diclofenac using Saccharomycescerevisiae as model system. We
      identified the involvement of several mitochondrial proteins, a transporter and
      cytochrome P450 activity in diclofenac toxicity. In this study, we investigated
      if these processes are also involved in the toxicity of other NSAIDs. We divided
      the NSAIDs into three classes based on their toxicity mechanisms. Class I
      consists of diclofenac, indomethacin and ketoprofen. Mitochondrial respiration
      and reactive oxygen species (ROS) play a major role in the toxicity of this
      class. Metabolism by cytochrome P450s further increases their toxicity, while ABC
      transporters decrease the toxicity. Mitochondria and oxidative metabolism also
      contribute to toxicity of class II drugs ibuprofen and naproxen, but another
      cellular target dominates their toxicity. Interestingly, ibuprofen was the only
      NSAID that was unable to induce upregulation of the multidrug resistance
      response. The class III NSAIDs sulindac, ketorolac and zomepirac were relatively
      non-toxic in yeast. In conclusion, we demonstrate the use of yeast to investigate
      the mechanisms underlying the toxicity of structurally related drugs.

PMID- 22138570
TI  - Vasomotor symptoms and negative affect:  time to act.

PMID- 22138571
TI  - Urine leakage:  menopause or normal aging?

PMID- 22138572
TI  - Hormone therapy and vasomotor symptoms.

PMID- 22138575
TI  - Autophagic targeting of Src promotes cancer cell survival following reduced FAK
      signalling.
AB  - Here we describe a mechanism that cancer cells use to survive when flux through
      the Src/FAK pathway is severely perturbed. Depletion of FAK, detachment of FAK
      proficient cells or expression of non-phosphorylatable FAK proteins causes
      sequestration of active Src away from focal adhesions into intracellular puncta
      that co-stain with several autophagy regulators. Inhibition of autophagy results
      in restoration of active Src at peripheral adhesions, and this leads to cancer
      cell death. Autophagic targeting of active Src is associated with a Src-LC3B
      complex, and is mediated by c-Cbl. However, this is independent of c-Cbl E3
      ligase activity, but is mediated by an LC3-interacting region. Thus, c-Cbl
      mediated autophagic targeting of active Src can occur in cancer cells to maintain
      viability when flux through the integrin/Src/FAK pathway is disrupted. This
      exposes a previously unrecognized cancer cell vulnerability that may provide a
      new therapeutic opportunity.

PMID- 22138576
TI  - Puma and p21 represent cooperating checkpoints limiting self-renewal and
      chromosomal instability of somatic stem cells in response to telomere
      dysfunction.
AB  - The tumour suppressor p53 activates Puma-dependent apoptosis and p21-dependent
      cell-cycle arrest in response to DNA damage. Deletion of p21 improved stem-cell
      function and organ maintenance in progeroid mice with dysfunctional telomeres,
      but the function of Puma has not been investigated in this context. Here we show
      that deletion of Puma improves stem- and progenitor-cell function, organ
      maintenance and lifespan of telomere-dysfunctional mice. Puma deletion impairs
      the clearance of stem and progenitor cells that have accumulated DNA damage as a
      consequence of critically short telomeres. However, further accumulation of DNA
      damage in these rescued progenitor cells leads to increasing activation of p21.
      RNA interference experiments show that upregulation of p21 limits proliferation
      and evolution of chromosomal imbalances of Puma-deficient stem and progenitor
      cells with dysfunctional telomeres. These results provide experimental evidence
      that p53-dependent apoptosis and cell-cycle arrest act in cooperating checkpoints
      limiting tissue maintenance and evolution of chromosomal instability at stem- and
      progenitor-cell levels in response to telomere dysfunction. Selective inhibition
      of Puma-dependent apoptosis can result in temporary improvements in maintenance
      of telomere-dysfunctional organs.

PMID- 22138577
TI  - Polarized cell growth in Arabidopsis requires endosomal recycling mediated by
      GBF1-related ARF exchange factors.
AB  - Polarized tip growth is a fundamental cellular process in many eukaryotic
      organisms, mediating growth of neuronal axons and dendrites or fungal hyphae. In
      plants, pollen and root hairs are cellular model systems for analysing tip
      growth. Cell growth depends on membrane traffic. The regulation of this membrane
      traffic is largely unknown for tip-growing cells, in contrast to cells exhibiting
      intercalary growth. Here we show that in Arabidopsis, GBF1-related exchange
      factors for the ARF GTPases (ARF GEFs) GNOM and GNL2 play essential roles in
      polar tip growth of root hairs and pollen, respectively. When expressed from the
      same promoter, GNL2 (in contrast to the early-secretory ARF GEF GNL1) is able to
      replace GNOM in polar recycling of the auxin efflux regulator PIN1 from endosomes
      to the basal plasma membrane in non-tip growing cells. Thus, polar recycling
      facilitates polar tip growth, and GNL2 seems to have evolved to meet the specific
      requirement of fast-growing pollen in higher plants.

PMID- 22138578
TI  - Operational, quality, and risk management in the transfusion service: lessons
      learned.
AB  - For general health care, the difference between quality and safety has been
      unclear for measurable patient outcomes. In contrast, in the transfusion service
      (TS), the relationship between quality and safety has been direct and
      demonstrable. Case studies are summarized to illustrate the relationship between
      operations, quality management, and risk management in the TS. In blood
      availability for elective surgery over 3 audited intervals, the incidence of
      patients undergoing elective surgery without available crossmatched blood that
      had been requested was 1:333, 1:328, and 1:225 for pre-quality improvement, post
      quality improvement, and subsequent postintervention audit assessment,
      respectively. In event discovery reports (EDRs) over 2 years, incidence of
      biologic product deviation reports (Food and Drug Administration reportable) was
      successfully reduced from 60 biologic product deviation reports (12%) of 507 EDRs
      in 2009 to 42 (12%) of 336 EDRs in 2010. In wrong blood in tube, 102 specimens
      were identified (by a change in patient's ABO/Rh) from 176,711 type and
      screen/cross-match specimens received over a 5-year interval, detected either by
      previous patient record of ABO/Rh or by a second specimen for blood type
      confirmation implemented in our TS for the last 3 years. No known cases of
      "mismatched" red blood cell transfusion have occurred during this interval. There
      is an inverse relationship between resources/time expended on quality and risk
      management relative to volumes of operations in the TS. Laboratory-based
      initiatives that improve patient safety and clinical outcomes need to have
      resources aligned with the personnel and time required for quality management and
      risk management.

PMID- 22138579
TI  - Adenosine A(2A) receptor ligation inhibits osteoclast formation.
AB  - Adenosine is generated in increased concentrations at sites of injury/hypoxia and
      mediates a variety of physiological and pharmacological effects via G protein
      coupled receptors (A(1), A(2A), A(2B), and A(3)). Because all adenosine receptors
      are expressed on osteoclasts, we determined the role of A(2A) receptor in the
      regulation of osteoclast differentiation. Differentiation and bone resorption
      were studied as the macrophage colony-stimulating factor-1-receptor activator of
      NF-kappaB ligand formation of multinucleated tartrate-resistant acid phosphatase
      (TRAP)-positive cells from primary murine bone marrow-derived precursors. A(2A)
      receptor and osteoclast marker expression levels were studied by RT-PCR. Cytokine
      secretion was assayed by enzyme-linked immunosorbent assay. In vivo examination
      of A(2A) knockout (KO)/control bones was determined by TRAP staining, micro
      computed tomography, and electron microscopy. The A(2A) receptor agonist,
      CGS21680, inhibited osteoclast differentiation and function (half maximal
      inhibitory concentration, 50 nmol/L), increased the percentage of immature
      osteoclast precursors, and decreased IL-1beta and tumor necrosis factor-alpha
      secretion, an effect that was reversed by the A(2A) antagonist, ZM241385.
      Cathepsin K and osteopontin mRNA expression increased in control and ZM241385
      pretreated osteoclasts, and this was blocked by CGS21680. Micro-computed
      tomography of A(2A)KO mouse femurs showed a significantly decreased bone
      volume/trabecular bone volume ratio, decreased trabecular number, and increased
      trabecular space. A(2A)KO femurs showed an increased TRAP-positive osteoclast.
      Electron microscopy in A(2A)KO femurs showed marked osteoclast membrane folding
      and increased bone resorption. Thus, adenosine, acting via the A(2A) receptor,
      inhibits macrophage colony-stimulating factor-1-receptor activator of NF-kappaB
      ligand-stimulated osteoclast differentiation and may regulate bone turnover under
      conditions in which adenosine levels are elevated.

PMID- 22138580
TI  - TRIM29 functions as a tumor suppressor in nontumorigenic breast cells and
      invasive ER+ breast cancer.
AB  - Tripartite motif-containing 29 (TRIM29) is a member of the TRIM protein family
      that has been implicated in hematologic and solid tumor cancers. We found that
      TRIM29 functions as a tumor suppressor in both the nontumorigenic MCF10A
      [estrogen receptor (ER)-/TRIM29+] breast cell line and the invasive MCF7
      (ER+/TRIM29-) breast cell line. Silencing TRIM29 in MCF10A cells resulted in
      preneoplastic changes that included loss of polarity in three-dimensional
      culture, increased proliferation, anchorage-independent growth, and increased
      migration and invasion. Conversely, the introduction of TRIM29 into MCF7 cells
      caused reversion to a less aggressive phenotype by antagonizing the growth effect
      of 17beta-estradiol. The interaction between TRIM29 and ER signaling in MCF7
      cells was supported by a reduction in ERE binding in the presence of TRIM29 and
      suppression of ER-dependent gene expression of TFF1, FOS, and GREB1. By
      microarray analyses, we showed that younger women (<55 years of age) with early
      stage, ER+ breast cancer who were given no adjuvant systemic therapy had a
      significantly lower risk of relapse when their tumor had high TRIM29 expression
      (P = 0.02). This effect was not observed in older women (>55 years of age) and
      thus may be due to menopause and loss of circulating estrogens. Our results
      suggest that loss of TRIM29 expression in normal breast luminal cells can
      contribute to malignant transformation and lead to progression of ER+ breast
      cancer in premenopausal women.

PMID- 22138581
TI  - Radiation-induced increase in cell migration and metastatic potential of cervical
      cancer cells operates via the K-Ras pathway.
AB  - Radiotherapy is a well established treatment for cervical cancer, the second most
      common cancer in women worldwide. However, metastasis often circumvents the
      efficacy of radiotherapy. This study was conducted to elucidate the molecular
      mechanism of radioresistance-associated metastatic potential of cervical cancer
      cells. We established three radioresistant cervical cancer cell lines by exposure
      of cells to a sublethal dose of radiation and screened for lines that exhibited
      an increased migration phenotype for at least 6 months before undertaking
      mechanistic studies. Radiation-associated metastatic potential was evaluated
      using a wound-healing assay, time-lapse recording, and cell locomotion into the
      lungs of BALB/c nude mice. The radioresistant C33A and CaSki cell lines, but not
      the radioresistant HeLa cell line, exhibited significantly increased cell
      migration and wound healing than did wild-type cells. Furthermore, K-Ras played a
      prometastatic role via the activation of c-Raf/p38, whereas interference of those
      mediators via either RNA interference-mediated knockdown or the use of chemical
      inhibitors substantially reversed the radioresistance-associated increase in cell
      migration. Clinical examination further showed the relative up-regulation of the
      K-Ras/c-Raf/p38 pathway in locally recurring tumors and distant metastases
      compared with in the primary cervical tumor. These findings demonstrate that a
      sublethal dose of radiation can enhance the metastatic potential of human
      cervical cancer cells via K-Ras/c-Raf/p38 signaling, highlighting the potential
      development of specific inhibitors for reducing metastatic potential during
      radiotherapy.

PMID- 22138582
TI  - FOXA1 promotes tumor progression in prostate cancer and represents a novel
      hallmark of castration-resistant prostate cancer.
AB  - Forkhead box protein A1 (FOXA1) modulates the transactivation of steroid hormone
      receptors and thus may influence tumor growth and hormone responsiveness in
      prostate cancer. We therefore investigated the correlation of FOXA1 expression
      with clinical parameters, prostate-specific antigen (PSA) relapse-free survival,
      and hormone receptor expression in a large cohort of prostate cancer patients at
      different disease stages. FOXA1 expression did not differ significantly between
      benign glands from the peripheral zone and primary peripheral zone prostate
      carcinomas. However, FOXA1 was overexpressed in metastases and particularly in
      castration-resistant cases, but was expressed at lower levels in both normal and
      neoplastic transitional zone tissues. FOXA1 levels correlated with higher pT
      stages and Gleason scores, as well as with androgen (AR) and estrogen receptor
      expression. Moreover, FOXA1 overexpression was associated with faster biochemical
      disease progression, which was pronounced in patients with low AR levels.
      Finally, siRNA-based knockdown of FOXA1 induced decreased cell proliferation and
      migration. Moreover, in vitro tumorigenicity was inducible by ARs only in the
      presence of FOXA1, substantiating a functional cooperation between FOXA1 and AR.
      In conclusion, FOXA1 expression is associated with tumor progression,
      dedifferentiation of prostate cancer cells, and poorer prognosis, as well as with
      cellular proliferation and migration and with AR signaling. These findings
      suggest FOXA1 overexpression as a novel mechanism inducing castration resistance
      in prostate cancer.

PMID- 22138583
TI  - Placental syndecan expression is altered in human idiopathic fetal growth
      restriction.
AB  - Pregnancy represents a hypercoagulable state characterized by increased thrombin
      generation. However, placentas from fetal growth restriction (FGR) pregnancies
      are characterized by increased fibrin deposition and thrombi in the vasculature,
      indicative of a further increase in thrombin activation and a disturbance in
      coagulation in this clinical setting. The cause of the coagulation disturbance
      observed in FGR pregnancies is currently unknown. Anticoagulant mechanisms are
      crucial in the regulation of thrombin activity, and current evidence suggests
      that syndecans are the principal placental anticoagulant proteoglycans. The aim
      of this study was to determine the localization, distribution, and expression of
      syndecans 1 to 4 in placentas complicated by idiopathic FGR compared with
      gestation-matched controls. Immunohistochemistry results revealed that all of the
      syndecans were localized to cells located closely to the maternal and fetal
      circulation. The mRNA and protein expression levels of both syndecan 1 and
      syndecan 2 were significantly decreased in FGR samples compared with controls.
      This is the first study to demonstrate the differential expression of syndecans 1
      to 4 in idiopathic FGR placentas compared with controls. Reduced levels of
      syndecan expression may result in increased placental thrombosis in the
      uteroplacental circulation and may therefore contribute to the pathogenesis of
      FGR.

PMID- 22138585
TI  - Noninvasive, objective, multimodal tear dynamics evaluation of 5 over-the-counter
      tear drops in a randomized controlled trial.
AB  - PURPOSE: To assess the ability of a noninvasive, objective, multimodal system to
      compare the efficacy and optical quality of 4 different groups of 5 over-the
      counter tear drops. METHODS: Wavefront sensing and optical coherence tomography
      (OCT) were used to objectively assess visual quality and tear volume,
      respectively, after the over-the-counter tear drops [2 polyethylene glycol (PEG)
      400, 1 carboxymethyl cellulose (CMC), 1 polyvinyl alcohol/PEG-400 (PVA), and 1
      glycerine/polysorbate-80] were administered to 23 patients with aqueous-deficient
      dry eye in a randomized, controlled, double-masked trial. Measurements at each of
      the 5 visits were taken from both eyes at baseline and 5, 20, and 40 minutes
      after drop instillation. RESULTS: At 5 minutes after drop instillation, the 2 PEG
      drops showed significant worsening of visual quality (-128.87%, P = 0.001)
      compared with CMC, PVA, and glycerine drops. Tear volume was elevated
      significantly with PEG and CMC drops at 5 minutes (+33.2%, P = 0.002; +29.9%, P <
      0.001) compared with the other groups. Subjects with a Schirmer score of less
      than 5 mm at 5 minutes showed improvement in visual quality with PEG drops,
      whereas those with a fluorescein staining score of 1 to 2 showed improvement with
      both PEG and CMC drops. A trend toward decreasing visual quality with increasing
      tear meniscus was noted. CONCLUSIONS: Noninvasive multimodal imaging has the
      potential to evaluate tear dynamics and the efficacy of artificial tears
      objectively. Certain artificial tear components and the temporary increase in
      tear volume after instillation of artificial tears may contribute to transient
      reduction of visual quality.

PMID- 22138586
TI  - "PISK-itis" or "PISK-opathy"?

PMID- 22138587
TI  - A new long-acting liposomal topical antifungal formula: human clinical study.
AB  - PURPOSE: To study the clinical effect of a topical controlled-release ophthalmic
      fluconazole liposomal formulation on patients with Candida keratitis. METHODS:
      Eleven eyes of 11 patients with Candida albicans corneal fungal infection (proved
      by cultures) were included in this study. All were treated with topical liposomal
      fluconazole (2 mg/mL) 3 times daily. The response to the treatment was divided
      into 3 categories: complete improvement, complete healing with scar formation at
      the end of 1 month; partial improvement, decrease in the ulcer size at the end of
      1 month; and no improvement, includes extension of ulcer size and/or perforation
      that necessitates other approaches of management. The patients were examined
      daily over a 30-day period, and the results were recorded. RESULTS: Eleven eyes
      with C. albicans as proved with laboratory cultures were included in this study
      (7 men and 4 women). Three of the patients included in this study had diabetes
      mellitus, and 2 patients had rheumatoid arthritis. Mean corneal ulcer diameter
      (mean of both horizontal and vertical diameters) was 5.5 mm (range, 3.5-6.5 mm).
      Mean duration of the ulcers at presentation was 7.6 days (range, 3-14 days).
      Eight patients improved after 1 month, whereas 1 patient had partial improvement
      and 2 patients did not improve and underwent amniotic membrane transplantation.
      One of the nonimproved patients progressed to perforation, and keratoplasty was
      performed. Mean decimal notation best-corrected visual acuity on presentation was
      0.06, which was not improved at the end of the study. CONCLUSIONS: Therapy with
      topical liposomal fluconazole (2 mg/mL) carries a high success rate and fast
      effect in treating patients with C. albicans keratitis.

PMID- 22138588
TI  - Flow injection tandem mass spectrometric measurement of ceramides of multiple
      chain lengths in biological samples.
AB  - A method is presented for the measurement of ceramide species in biological
      fluids using flow injection tandem mass spectrometry. Ceramides are important
      signaling compounds in a number of cell:cell interactions including apoptosis and
      neurodegeneration. Because of the large number of potential fatty acid
      constituent moieties on ceramide molecules, a method which accurately
      distinguishes different chain-length species was required. The present method
      does not require HPLC separation and is designed to be applicable to high
      throughput analysis required for clinical studies. We provide a reference range
      for all measurable ceramide species in normal human plasma and an example of the
      utility of the assay in providing biomarkers in an in vitro apoptotic cell death
      study using murine hematopoietic cells treated with daunorubicin.

PMID- 22138589
TI  - Quantification of the Fabry marker lysoGb3 in human plasma by tandem mass
      spectrometry.
AB  - Morbus Fabry is a hereditary metabolic disorder with low prevalence and late
      clinical manifestation. A defect in the alpha-galactosidase gene leads to
      lysosomal accumulation of the glycolipid globotriaosylceramide (Gb3). Gb3 may be
      used for monitoring of enzyme replacement therapy (ERT), but diagnostic
      sensitivity is limited. Recently, globotriaosylsphingosine (lysoGb3) was
      introduced as a promising new marker with significantly better sensitivity. For
      Fabry diagnosis, clinical studies and possible therapy monitoring, we established
      a fast and reliable LC-MS/MS assay for quantification of lysoGb3 in human plasma.
      Protein precipitation and glycolipid extraction from EDTA plasma was performed
      using acetone/methanol. Samples were analyzed by UPLC-MS/MS in MRM mode. In
      contrast to HPLC with fluorescence detection, the LC-MS/MS method requires no
      derivatization, less sample preparation and less instrument analysis time (<3
      min). As internal standard (ISTD), a glycine derivative of lysoGb3 was
      synthesized, and the product was purified by HPLC. ISTD properties such as
      polarity (affecting extraction and elution), ionization and fragmentation pathway
      were almost identical compared to the analyte. The new LC-MS/MS assay for the
      Fabry marker lysoGb3 shows good performance and allowed for better discrimination
      between Fabry patients and controls than Gb3.

PMID- 22138590
TI  - Selective extraction and separation of oxymatrine from Sophora flavescens Ait.
      extract by silica-confined ionic liquid.
AB  - This study highlighted the application of a two-stepped extraction method for
      extraction and separation of oxymatrine from Sophora flavescens Ait. extract by
      utilizing silica-confined ionic liquids as sorbent. The optimized silica-confined
      ionic liquid was firstly mixed with plant extract to adsorb oxymatrine.
      Simultaneously, some interference, such as matrine, was removed. The obtained
      suspension was then added to a cartridge for solid phase extraction. Through
      these two steps, target compound was adequately separated from interferences with
      93.4% recovery. In comparison with traditional solid phase extraction, this
      method accelerates loading and reduces the use of organic solvents during
      washing. Moreover, the optimization of loading volume was simplified as
      optimization of solid/liquid ratio.

PMID- 22138591
TI  - Recovery of gold as a type of porous fiber by using biosorption followed by
      incineration.
AB  - This study introduces a new process for the recovery of gold in porous fiber form
      by the incineration of Au-loaded biosorbent fiber from gold-cyanide solutions.
      For the recovery of gold from such aqueous solutions, polyethylenimine (PEI)
      modified bacterial biosorbent fiber (PBBF) and PEI-modified chitosan fiber (PCSF)
      were developed and used. The maximum uptakes of Au(I) ions were estimated as
      421.1 and 251.7 mg/g at pH 5.5 for PBBF and PCSF, respectively. Au-loaded
      biosorbents were freeze-dried and then incinerated to oxidize their organic
      constituents while simultaneously obtaining reduced gold. As a result, porous
      metallic gold fibers were obtained with 60 MUm of diameter. Scanning electron
      microscopic (SEM) analysis and mercury porosimetry revealed the fibers to have 60
      MUm of diameter and to be highly porous and hollow. The proposed process
      therefore offers the potential for the efficient recovery of metallic porous gold
      fibers using combined biosorption and incineration.

PMID- 22138592
TI  - The effect of particle size and thermal pre-treatment on the methane yield of
      four agricultural by-products.
AB  - One way to optimize methane production in anaerobic digestion plants is to
      substitute ligno-cellulosic by-products for crops traditionally used as energy
      sources. However, using these by-products requires introduction of a pre
      treatment system to minimize energy input and maximize energy output for an
      improved net energy equation. In this study, four agricultural byproducts (wheat,
      barley, rice straw and maize stalks) underwent various mechanical and thermal
      treatments prior to anaerobic digestion including particle size reduction to 5.0,
      2.0, 0.5, and 0.2 cm and heat application to 90  degrees C and 120  degrees C.
      Mechanical pre-treatment increased byproduct methane yields more than 80%;
      thermal pre-treatment improved yields more than 60% for wheat and barley straw.
      Pre-treating wheat straw improved methane yields most, regardless of whether the
      method was thermal or mechanical. An electric net energy balance was also
      completed to analyze the feasibility of the pre-treatments according to input and
      output of energy.

PMID- 22138593
TI  - Enzymatic acylation of starch.
AB  - Starch a cheap, abundant and renewable natural material has been chemically
      modified for many years. The popular modification acylation has been used to
      adjust rheological properties as well as deliver polymers with internal
      plasticizers and other potential uses. However the harsh reaction conditions
      required to produce these esters may limit their use, especially in sensitive
      applications (foods, pharmaceuticals, etc.). The use of enzymes to catalyse
      acylation may provide a suitable alternative due to high selectivities and mild
      reaction conditions. Traditional hydrolase-catalysed synthesis in non-aqueous
      apolar media is hard due to lack of polysaccharide solubility. However, acylated
      starch derivatives have recently been successfully produced in other non
      conventional systems: (a) surfactant-solubilised subtilisin and suspended amylose
      in organic media; (b) starch nanoparticles dispersed in organic medium with
      immobilised lipase; (c) aqueous starch gels with lipase and dispersed fatty
      acids. We attempt a systematic review that draws parallels between the seemingly
      unrelated approaches described.

PMID- 22138594
TI  - Optimization of AFEXTM pretreatment conditions and enzyme mixtures to maximize
      sugar release from upland and lowland switchgrass.
AB  - Switchgrass is a North American grass that is considered to be a highly promising
      herbaceous bioenergy feedstock. Differences in processing conditions and yields
      specifically related to switchgrass cultivar or cytotype (upland or lowland) can
      be confounded by differences in harvest date or region of growth. For this
      research, AFEXTM pretreatment conditions and hydrolysis enzyme mixtures were
      statistically optimized for Alamo (lowland) and Shawnee (upland) switchgrass that
      had been harvested in December in Oklahoma. Optimal pretreatment conditions and
      enzyme mixtures were almost identical for both varieties and gave similar mass
      sugar yields. Inclusion of hemicellulases in the enzyme mixture maintained total
      sugar yields with 50% reduction in enzyme loading. Regardless of variety, the
      biorefinery should be able to obtain high sugar yields using the same
      pretreatment and hydrolysis conditions to process switchgrass grown under the
      same environmental conditions, in the same location, and harvested at the same
      time of the year.

PMID- 22138595
TI  - Continuous biodiesel production in a fixed bed reactor packed with anion-exchange
      resin as heterogeneous catalyst.
AB  - A continuous biodiesel production from the transesterification of soybean oil
      with methanol was investigated in a fixed bed reactor packed with D261 anion
      exchange resin as a heterogeneous catalyst. The conversion to biodiesel achieved
      95.2% within a residence time 56 min under the conditions: reaction temperature
      of 323.15K, n-hexane/soybean oil weight rate of 0.5, methanol/soybean oil molar
      ratio of 9:1 and feed flow rate of 1.2 ml/min. The resin can be regenerated in
      situ and restored to the original activity to achieve continuous production after
      the resin deactivation. The product obtained was mainly composed of methyl
      esters. No glycerol in the product was detected due to the resin adsorbing
      glycerol in the fixed bed, which solved the issue of glycerol separation from
      biodiesel. It is believed that the fixed bed reactor with D261 has a potential
      commercial application in the transesterification of triglyceride.

PMID- 22138596
TI  - Polyamines reduce oxidative stress in Escherichia coli cells exposed to
      bactericidal antibiotics.
AB  - Bactericidal antibiotics (fluoroquinolones, aminoglycosides and cephalosporins)
      at their sublethal concentrations were able to produce hydroxyl radicals,
      hydrogen peroxide and superoxide anions (ROS) in Escherichia coli cells, which
      resulted in damage to proteins and DNA. The cells responded to oxidative stress
      by a 2-3-fold increase in cell polyamines (putrescine, spermidine) produced as a
      consequence of upregulation of ornithine decarboxylase (ODC). Relief of oxidative
      stress by cessation of culture aeration or addition of antioxidants substantially
      diminished or even completely abolished polyamine accumulation observed in
      response to antibiotics. Alternatively, inhibition of polyamine synthesis
      resulted in enhancement of oxidative stress in antibiotic-processed cells. When
      added to antibiotic-inhibited culture, polyamines reduced intracellular ROS
      production and thereby prevented damage to proteins and DNA. These effects
      eventually resulted in a substantial increase in cell viability, growth recovery
      and antibiotic resistance that were more strongly expressed in polyamine
      deficient mutants.

PMID- 22138597
TI  - Enteric fever in returning travellers: role of outpatient parenteral antibiotic
      therapy.

PMID- 22138598
TI  - Lung and pharyngeal abscess caused by enterotoxin G- and I-producing
      Staphylococcus aureus.
AB  - We report a particularly serious case of extensive meticillin sensitive
      Staphylococcal lung and pharyngeal abscess. Our patient had no significant risk
      factors for severe infection. The detection of enterotoxin G and I here suggest
      that when present together, these toxins work synergistically to produce a more
      virulent strain of Staphylococcus aureus.

PMID- 22138599
TI  - Campylobacter fetus bacteremia in a young healthy adult transmitted by khat
      chewing.
AB  - Campylobacter fetus is a pathogen affecting almost exclusively patients with
      immunosuppression and chronic debilitating diseases. We report the case of a
      healthy young man with C. fetus bacteremia presenting with fever, hypotension and
      meningitis. The patient had no exposure to contaminated sources except from khat
      chewing, which we describe as a possible source of transmission for the first
      time.

PMID- 22138600
TI  - Colonisation and infection due to Enterobacteriaceae producing plasmid-mediated
      AmpC beta-lactamases.
AB  - OBJECTIVES: To investigate the epidemiology and clinical features of infections
      caused by Enterobacteria producing plasmid-mediated AmpC beta-lactamases (pAmpC),
      which are emerging as a cause of resistance to extended-spectrum cephalosporins.
      METHODS: A prospective multicentre cohort of patients with infection/colonisation
      due to pAmpC-producing Enterobacteriaceae was performed in 7 Spanish hospitals
      from February throughout July 2009. pAmpCs were characterised by PCR and
      sequencing. RESULTS: 140 patients were included; organisms isolated were
      Escherichia coli (n = 100), Proteus mirabilis (n = 20), Klebsiella pneumoniae (n
      = 17), and others (n = 3). Overall, 90% had a chronic underlying condition. The
      acquisition was nosocomial in 43%, healthcare-associated in 41% (14% of those
      were nursing home residents), and community in 16%. Only 5% of patients had no
      predisposing feature for infection with multidrug-resistant bacteria. Nineteen
      percent of patients were bacteraemic. Inappropriate empirical therapy was
      administered to 81% of bacteraemic patients, who had a crude mortality rate of
      48%. The most frequent enzyme was CMY-2 (70%, predominantly in E. coli and P.
      mirabilis) followed by DHA-1 (19%, predominantly in K. pneumoniae). CONCLUSION:
      pAmpC-producing Enterobacteriaceae caused nosocomial, healthcare-associated and
      community infections mainly in predisposed patients. Invasive infections were
      associated with high mortality which might be partly related to inappropriate
      empirical therapy.

PMID- 22138601
TI  - Control measures for invasive group A streptococci (iGAS) outbreaks in care
      homes.
AB  - OBJECTIVES: The incidence of invasive group A streptococcal infections (iGAS) is
      increasing in Europe, with a particularly high morbidity and mortality in the
      elderly. Control of outbreaks in care homes is therefore important; but is
      unclear how best to manage these incidents. We attempted to identify which
      control measures are most likely to be effective. METHODS: We undertook
      literature searches using PubMed and Google Scholar and contacted colleagues in
      Health Protection Units in England for unpublished outbreaks. RESULTS: We
      identified 31 outbreaks; of which 20 had sufficient detail for further analysis.
      Overall carriage rates of GAS in care home residents identified in outbreak
      investigations were 4.7%, and in staff 3.2%. In 8 outbreaks mass antibiotic
      prophylaxis was offered, in 9 selective prophylaxis only and in 3 none at all.
      Surveillance swabbing had limited influence on decisions regarding prophylaxis. A
      few papers mentioned the role of environmental contamination and the risk from an
      affected roommate. CONCLUSIONS: Pooling of results from these outbreaks failed to
      suggest any clear advantage to either a selective or mass antibiotic prophylaxis
      strategy in controlling spread. Systematic investigation and data collection from
      future outbreaks could be of benefit in informing future policy.

PMID- 22138602
TI  - Clinical characteristics and outcomes of diabetic patients who were hospitalised
      with 2009 pandemic influenza A H1N1 infection.
AB  - OBJECTIVES: To describe demographic and clinical data and outcomes of severe
      cases of 2009 pandemic influenza A H1N1 (pH1N1) infections for persons with
      diabetes. METHODS: We selected all person with diabetes (N = 252) among severe
      laboratory confirmed cases reported to the Spanish Surveillance System for
      detection of pH1N1 from June through December, 2009. One patient without diabetes
      matched by age and sex was selected. Collected variables included demographic
      characteristics, underlying medical conditions, outcome, clinical course and
      treatment. RESULTS: Among those suffering diabetes only 15.9% did not report any
      other underlying condition. 38% of diabetic patients and 27.4% of non diabetic
      patients were admitted to ICU (p = 0.008). Thirty subjects suffering diabetes and
      fifteen without the disease died (11.9% vs. 6%[p = 0.019]). Multivariable
      analysis showed that the independent risk factors for ICU admission or death were
      suffering cardiovascular disease (OR = 2.28), morbid obesity (OR = 2.08) and
      antiviral treatment started after 48 h of onset of symptoms (OR = 1.89).
      Suffering diabetes was not independent risk factors for ICU admission or death
      after adjusting for covariates. CONCLUSIONS: The worse outcome among diabetes
      sufferers could be a consequence of the higher prevalence of comorbid underlying
      medical conditions but not diabetes itself. Further prospective studies are
      needed to verify these results.

PMID- 22138603
TI  - The cellular and molecular origin of reactive oxygen species generation during
      myocardial ischemia and reperfusion.
AB  - Myocardial ischemia-reperfusion injury is an important cause of impaired heart
      function in the early postoperative period subsequent to cardiac surgery.
      Reactive oxygen species (ROS) generation increases during both ischemia and
      reperfusion and it plays a central role in the pathophysiology of intraoperative
      myocardial injury. Unfortunately, the cellular source of these ROS during
      ischemia and reperfusion is often poorly defined. Similarly, individual ROS
      members tend to be grouped together as free radicals with a uniform reactivity
      towards biomolecules and with deleterious effects collectively ascribed under the
      vague umbrella of oxidative stress. This review aims to clarify the identity,
      origin, and progression of ROS during myocardial ischemia and reperfusion.
      Additionally, this review aims to describe the biochemical reactions and cellular
      processes that are initiated by specific ROS that work in concert to ultimately
      yield the clinical manifestations of myocardial ischemia-reperfusion. Lastly,
      this review provides an overview of several key cardioprotective strategies that
      target myocardial ischemia-reperfusion injury from the perspective of ROS
      generation. This overview is illustrated with example clinical studies that have
      attempted to translate these strategies to reduce the severity of ischemia
      reperfusion injury during coronary artery bypass grafting surgery.

PMID- 22138604
TI  - Matrix metalloproteinases as therapeutic targets in protozoan parasitic
      infections.
AB  - Matrix metalloproteinases (MMPs) are associated with processes of tissue
      remodeling and are expressed in all infections with protozoan parasites. We here
      report the status of MMP research in malaria, trypanosomiasis, leishmaniasis and
      toxoplasmosis. In all these infections, the balances between MMPs and endogenous
      MMP inhibitors are disturbed, mostly in favor of active proteolysis. When the
      infection is associated with leukocyte influx into specific organs,
      immunopathology and collateral tissue damage may occur. These pathologies include
      cerebral malaria, sleeping sickness (human African trypanosomiasis), Chagas
      disease (human American trypanosomiasis), leishmaniasis and toxoplasmic
      encephalitis in immunocompromised hosts. Destruction of the integrity of the
      blood-brain barrier (BBB) is a common denominator that may be executed by
      leukocytic MMPs under the control of host cytokines and chemokines as well as
      influenced by parasite products. Mechanisms by which parasite-derived products
      alter host expression of MMP and endogenous MMP inhibitors, have only been
      described for hemozoin (Hz) in malaria. Hence, understanding these interactions
      in other parasitic infections remains an important challenge. Furthermore, the
      involved parasites are also known to produce their own metalloproteinases, and
      this forms an extra stimulus to investigate MMP inhibitory drugs as therapeutics.
      MMP inhibitors (MMPIs) may dampen collateral tissue damage, as is anecdotically
      reported for tetracyclines as MMP regulators in parasite infections.

PMID- 22138605
TI  - Evaluation of cell death after treatment with extracorporeal photopheresis.
AB  - The aim of our study is to assess the mortality of leukocytes during
      extracorporeal photopheresis. Sixty-three photopheresis performed on 13 patients
      affected by chronic GvHD were evaluated. Samples were analyzed using a
      FACSCalibur flow cytometer. Apoptosis and necrosis of limphomononuclear cells
      dramatically increased after the apheretic procedure. We found a further increase
      of apoptotic and necrotic limphomononuclear cells after treatment with 8-MOP and
      UVA (p<=0.05). Our data suggested that the immunomodulatory effects of
      extracorporeal photopheresis, triggered by circulating apoptotic or necrotic
      cells, could play an important role in the treatment of GvHD with this procedure.

PMID- 22138606
TI  - Blocking glomerular immunoglobulin deposits in a mouse model of lupus nephritis
      on indirect immunofluorescence with the use of Fab fragments.
AB  - One of the most characterized models of murine lupus nephritis is the [NZB*NZW]
      F1 female hybrid. Extended glomerular IgG deposits may pose an obstacle in
      studying molecules of interest via indirect immunofluorescence due to secondary
      antibodies non-specific binding to deposited IgG molecules. Application of Fab
      fragments may mitigate non-specific interactions in this mouse model.
      Specifically we provide evidence that blocking paratopic interactions of
      secondary antibodies with indigenous glomerular IgG deposits is possible. However
      the blocking effect seems to be related to the species used for secondary
      antibody production. Increased secondary antibody host species homology with the
      mouse could make blocking of non-specific binding via the use of Fab fragments
      impossible in this mouse model.

PMID- 22138607
TI  - Molecular-level characterization of probucol nanocrystal in water by in situ
      solid-state NMR spectroscopy.
AB  - The molecular state of colloidal probucol nanoparticles with additives was
      evaluated by (13)C in situ solid-state NMR spectroscopy. The nanoparticles were
      obtained by dispersing a ternary co-ground mixture of
      probucol/polyvinylpyrrolidon (PVP)/sodium dodecyl sulfate (SDS) in water. Their
      mean particle size was found to be approximately 150 nm by dynamic light
      scattering and cryogenic-scanning electron microscopy measurements. The results
      of the (13)C in situ solid-state NMR spectroscopy showed that probucol existed in
      the crystalline state (form I) in water. (13)C liquid-state NMR results indicated
      that PVP and SDS interacted with probucol in water. Their broad signals suggested
      that the surface interaction of the probucol nanocrystal with PVP and SDS
      stabilized the suspension. In addition, a freeze-dried sample of the suspension
      was studied by (13)C solid-state NMR and powder X-ray diffraction experiments,
      which confirmed the presence of the probucol nanocrystals. The combination of the
      in situ solid-state, solid-state, and liquid-state NMR measurement results
      provided molecular-level insights about the role of intermolecular interactions
      in the design of nanoformulations.

PMID- 22138608
TI  - Further improvement of orally disintegrating tablets using micronized
      ethylcellulose.
AB  - The aim of this study is to design a new orally disintegrating tablet (ODT)
      containing micronized ethylcellulose (MEC). The new ODT was prepared by physical
      mixing of rapidly disintegrating granules (RDGs) with MEC. To obtain RDGs,
      mannitol was spray-coated with a suspension of corn starch and crospovidone (9:1,
      w/w ratio) using a fluidized-bed granulator (suspension spray-coating method).
      The new ODTs were evaluated for their hardness, friability, thickness, internal
      structure (X-ray-CT scanning), in vivo disintegration time, and water absorption
      rate. Since MEC increases tablet hardness by increasing the contact frequency
      between the granules, the new ODTs could obtain high hardness (>50 N) and low
      friability (<0.5 %) with relatively low compression force. In addition, fine
      capillary channels formed in ODTs facilitated the wicking action and enabled
      rapid disintegration in vivo (<30 s). On the other hand, since MEC has low
      hygroscopicity, the tablet hardness of ODTs containing MEC remained high for 1
      month in high-humidity conditions. In conclusion, the new ODTs containing MEC
      developed in this study possessed superior properties for clinical use and are
      expected to be applied for a wide range of functionally released drugs for bitter
      taste masking, sustained release, and controlled release (pH-dependent film
      coating, matrix, and microcapsule).

PMID- 22138610
TI  - Regulation of alveolar fluid clearance and ENaC expression in lung by exogenous
      angiotensin II.
AB  - Angiotensin II (Ang II) has been demonstrated as a pro-inflammatory effect in
      acute lung injury, but studies of the effect of Ang II on the formation of
      pulmonary edema and alveolar filling remains unclear. Therefore, in this study
      the regulation of alveolar fluid clearance (AFC) and the expression of epithelial
      sodium channel (ENaC) by exogenous Ang II was verified. SD rats were anesthetized
      and were given Ang II with increasing doses (1, 10 and 100 MUg/kg per min) via
      osmotic minipumps, whereas control rats received only saline vehicle. AT1
      receptor antagonist ZD7155 (10 mg/kg) and inhibitor of cAMP degeneration rolipram
      (1 mg/kg) were injected intraperitoneally 30 min before administration of Ang II.
      The lungs were isolated for measurement of alveolar fluid clearance. The mRNA and
      protein expression of ENaC were detected by RT-PCR and Western blot. Exposure to
      higher doses of Ang II reduced AFC in a dose-dependent manner and resulted in a
      non-coordinate regulation of alpha-ENaC vs. the regulation of beta- and gamma
      ENaC, however Ang II type 1 (AT1) receptor antagonist ZD7155 prevented the Ang II
      induced inhibition of fluid clearance and dysregulation of ENaC expression. In
      addition, exposure to inhibitor of cAMP degradation rolipram blunted the Ang II
      induced inhibition of fluid clearance. These results indicate that through
      activation of AT(1) receptor, exogenous Ang II promotes pulmonary edema and
      alveolar filling by inhibition of alveolar fluid clearance via downregulation of
      cAMP level and dysregulation of ENaC expression.

PMID- 22138609
TI  - NF-kB-regulated micro RNAs (miRNAs) in primary human brain cells.
AB  - Micro RNAs (miRNAs), small and labile ~22 nucleotide-sized fragments of single
      stranded RNA, are important regulators of messenger (mRNA) complexity and in
      shaping the transcriptome of a cell. In this communication, we utilized amyloid
      beta 42 (Abeta42) peptides and interleukin-1beta (IL-1beta) as a combinatorial,
      physiologically-relevant stress to induce miRNAs in human primary neural (HNG)
      cells (a co-culture of neurons and astroglia). Specific miRNA up-regulation was
      monitored using miRNA arrays, Northern micro-dot blots and RT-PCR. Selective NF
      kB translocation and DNA binding inhibitors, including the chelator and anti
      oxidant pyrollidine dithiocarbamate (PDTC) and the polyphenolic resveratrol
      analog CAY10512 (trans-3,5,4'-trihydroxystilbene), indicated the NF-kB
      sensitivity of several brain miRNAs, including miRNA-9, miRNA-125b and miRNA
      146a. The inducible miRNA-125b and miRNA-146a, and their verified mRNA targets,
      including 15-lipoxygenase (15-LOX), synapsin-2 (SYN-2), complement factor H (CFH)
      and tetraspanin-12 (TSPAN12), suggests complex and highly interactive roles for
      NF-kB, miRNA-125b and miRNA-146a. These data further indicate that just two NF-kB
      mediated miRNAs have tremendous potential to contribute to the regulation of
      neurotrophic support, synaptogenesis, neuroinflammation, innate immune signaling
      and amyloidogenesis in stressed primary neural cells of the human brain.

PMID- 22138611
TI  - Chest wall kinematics in young subjects with Pectus excavatum.
AB  - Quantifying chest wall kinematics and rib cage distortion during ventilatory
      effort in subjects with Pectus excavatum (PE) has yet to be defined. We studied
      24 patients: 19 during maximal voluntary ventilation (MVV) and 5 during MVV and
      cycling exercise (CE). By optoelectronic plethysmography (OEP) we assessed
      operational volumes in upper rib cage, lower rib cage and abdomen. Ten age
      matched healthy subjects served as controls. Patients exhibited mild restrictive
      lung defect. During MVV end-inspiratory and end-expiratory volumes of chest wall
      compartments increased progressively in controls, whereas most patients avoided
      dynamic hyperinflation by setting operational volumes at values lower than
      controls. Mild rib cage distortion was found in three patients at rest, but
      neither in patients nor in controls did MVV or CE consistently affect coordinated
      motion of the rib cage. Rib cage displacement was not correlated with a CT-scan
      severity index. Conclusions, mild rib cage distortion rarely occurs in PE
      patients with mild restrictive defect. OEP contributes to clinical evaluation of
      PE patients.

PMID- 22138612
TI  - Pre-hatch lung development in the ostrich.
AB  - We studied development of the ostrich lung using light microscopy as well as
      electron microscopy techniques. At E24, the lung comprised a few epithelial
      tubes, interspersed with abundant mesenchyme with scattered profiles of incipient
      blood vessels. Between E24 and E39, the epithelial thickness was reduced by 90%
      from 13.5 +/- 0.41 MUm to 1.33 +/- 0.014 MUm (mean +/- SD, respectively). Atria
      were evident at E32, and by E35, the first portions of the blood-gas barrier
      (BGB) measuring 3.41 +/- 1.12 MUm were encountered. Gas exchange tissue was well
      formed by E39 with atria, infundibulae, air capillaries and a mature blood-gas
      barrier (BGB). BGB formation proceeded through the complex processes of
      secarecytosis and peremerecytosis, which entailed decapitation of epithelial
      cells by cutting or pinching off respectively and by E39, the BGB was thin at
      2.21 +/- 1.21 MUm. Vascular remodeling by intussusceptive angiogenesis was a late
      stage process mediated by intraluminal pillars in the pulmonary vasculature.

PMID- 22138613
TI  - Failure to register as a predictor of sex offense recidivism: the big bad wolf or
      a red herring?
AB  - This quasi-experimental study analyzed the recidivism outcomes of 1,125 sexual
      offenders in two groups. The first group comprised 644 registered sex offenders
      who were convicted of a sex crime and at some point failed to register after
      release from prison. The comparison group contained 481 registered sex offenders
      released from prison during a similar time frame who did not fail to register
      after their release. The groups were then tracked for both sexual and nonsexual
      offenses to determine whether failure to register under Megan's Law is predictive
      of reoffending. Failure to register was not a significant predictor of sexual
      recidivism, casting doubt on the belief that sex offenders who are noncompliant
      with registration are especially sexually dangerous. Few differences between
      groups were detected, but FTR offenders were more likely to have sexually
      assaulted a stranger and to have adult female victims, further challenging the
      stereotype of the child predator who absconds to evade detection. Potential
      policy implications are discussed.

PMID- 22138615
TI  - On the role of astrocytes in epilepsy: a functional modeling approach.
AB  - In the present research, we extend a biologically plausible cortical neural
      population model (CPM), which was developed previously in the literature, by
      integrating the functional role of astrocytes in the synaptic transmission in the
      model. In other words, the original CPM is modified to consider neuron-astrocyte
      interaction. Then, two modified CPMs (MCPMs) are coupled via excitatory synapses;
      the astrocytes are also coupled through gap junctions. Using the coupled MCPMs
      (CMCPMs), it is demonstrated that the healthy astrocytes provide appropriate
      feedback control in regulating neural activity. As a result, the astrocytes
      compensate the coupling variations between CPMs in order to maintain the normal
      level of synchronized behavior. Next, malfunction of astrocytes in the regulatory
      feedback loop as one of the plausible causes of seizures is investigated. In this
      way, dysfunctional astrocytes are not any more able to regulate the excessive
      increase of the inter-population coupling strength. Consequently, disruption of
      the homeostatic function of astrocytes may initiate the hypersynchronous firing
      of neurons. This suggests that the neuron-astrocyte interaction may represent a
      novel target to develop effective therapeutic strategies for epilepsy.

PMID- 22138614
TI  - The role of [18F]fluorodeoxyglucose positron emission tomography in thymic
      epithelial tumors.
AB  - The purpose of this study was to systemically review the available literature
      regarding the diagnostic performance of positron emission tomography (PET) using
      2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) in patients with thymic epithelial
      tumors. We reviewed 13 studies that evaluated the diagnostic role of thymic
      epithelial tumors with [18F]FDG-PET. [18F]FDG-PET is a useful radiological
      modality for differentiating between thymomas and thymic carcinoma. However,
      [18F]FDG-PET may not be useful for differentiating low-risk thymoma and high-risk
      thymoma. One paper reported that [18F]FDG-PET has a predictive significance for
      treatment and prognosis in thymic epithelial tumors. Two papers reported that the
      degree of [18F]FDG uptake in thymic epithelial tumors is based on glucose
      metabolism. [18F]FDG-PET may have a further use for radiological differential
      diagnosis of thymomas and thymic carcinomas.

PMID- 22138616
TI  - Childhood adversity and immune and inflammatory biomarkers associated with
      cardiovascular risk in youth: a systematic review.
AB  - BACKGROUND: Research suggests that adverse experiences in childhood affect the
      development of cardiovascular disease (CVD), and immune and inflammation
      dysregulation has been postulated to play role. However, it is unclear whether
      the effects of social adversity on immune-related biomarkers are evident in early
      life, and if these biomarkers may provide an early risk marker for targeting
      prevention and intervention. The purpose of this review is to evaluate research
      on the relationship between adversity and CVD-relevant immune biomarkers in
      youth, assess the consistency of the findings, and consider what additional
      research is needed. METHODS: PubMed and PsycINFO searches were conducted through
      September 2011. Studies were selected using criteria related to the childhood
      exposure, biomarker outcome, age range, and sample selection. Twenty articles
      were identified, examining associations between childhood adversity and immune
      biomarkers (assessed during childhood) that are potential risk markers for CVD
      later in life. RESULTS: Although childhood adversity was not consistently related
      to youth levels of inflammatory and other immune markers relevant to CVD, a trend
      toward positive findings was observed. No detectable patterns were evident based
      on measure of adversity, biomarker, study design, or sample size. CONCLUSIONS:
      Overall, our findings suggest this avenue of research is worth continued
      investigation. We offer recommendations for future research related to (1) study
      design and sample, (2) definition and measurement of adversity, (3) statistical
      analysis, and (4) outcomes that will help distinguish whether there are
      immunologic alterations related to adversity and subsequent CVD risk that can be
      reliably detected in childhood.

PMID- 22138617
TI  - ECVAM prevalidation study on in vitro cell transformation assays: general outline
      and conclusions of the study.
AB  - The potential for a compound to induce carcinogenicity is a key consideration
      when ascertaining hazard and risk assessment of chemicals. Among the in vitro
      alternatives that have been developed for predicting carcinogenicity, in vitro
      cell transformation assays (CTAs) have been shown to involve a multistage process
      that closely models important stages of in vivo carcinogenesis and have the
      potential to detect both genotoxic and non-genotoxic carcinogens. These assays
      have been in use for decades and a substantial amount of data demonstrating their
      performance is available in the literature. However, for the standardised use of
      these assays for regulatory purposes, a formal evaluation of the assays, in
      particular focusing on development of standardised transferable protocols and
      further information on assay reproducibility, was considered important to serve
      as a basis for the drafting of generally accepted OECD test guidelines. To
      address this issue, a prevalidation study of the CTAs using the BALB/c 3T3 cell
      line, SHE cells at pH 6.7, and SHE cells at pH 7.0 was coordinated by the
      European Centre for the Validation of Alternative Methods (ECVAM) and focused on
      issues of standardisation of protocols, test method transferability and within-
      and between-laboratory reproducibility. The study resulted in the availability of
      standardised protocols that had undergone prevalidation [1,2]. The results of the
      ECVAM study demonstrated that for the BALB/c 3T3 method, some modifications to
      the protocol were needed to obtain reproducible results between laboratories,
      while the SHE pH 6.7 and the SHE pH 7.0 protocols are transferable between
      laboratories, and results are reproducible within- and between-laboratories. It
      is recommended that the BALB/c 3T3 and SHE protocols as instituted in this
      prevalidation study should be used in future applications of these respective
      transformation assays. To support their harmonised use and regulatory
      application, the development of an OECD test guideline for the SHE CTAs, based on
      the protocol published in this issue, is recommended. The development of an OECD
      test guideline for the BALB/c 3T3 CTA should likewise be further pursued upon the
      availability of additional supportive data and improvement of the statistical
      analysis.

PMID- 22138618
TI  - Reduction of misleading ("false") positive results in mammalian cell genotoxicity
      assays. I. Choice of cell type.
AB  - Current in vitro mammalian cell genotoxicity assays show a high rate of positive
      results, many of which are misleading when compared with in vivo genotoxicity or
      rodent carcinogenicity data. P53-deficiency in many of the rodent cell lines may
      be a key factor in this poor predictivity. As part of an European Cosmetics
      Industry Association initiative for improvement of in vitro mammalian cell
      assays, we have compared several rodent cell lines (V79, CHL, CHO) with p53
      competent human peripheral blood lymphocytes (HuLy), TK6 human lymphoblastoid
      cells, and the human liver cell line, HepG2. We have compared in vitro
      micronucleus (MN) induction following treatment with 19 compounds that were
      accepted as producing misleading or "false" positive results in in vitro
      mammalian cell assays [6]. Of these, six chemicals (2-ethyl-1,3-hexandiol, benzyl
      alcohol, urea, sodium saccharin, sulfisoxazole and isobutyraldehyde) were not
      toxic and did not induce any MN at concentrations up to 10mM. d,l-Menthol and
      ethionamide induced cytotoxicity, but did not induce MN. o-Anthranilic acid was
      not toxic and did not induce MN in V79, CHL, CHO, HuLy and HepG2 cells up to
      10mM. Toxicity was induced in TK6 cells, although there were no increases in MN
      frequency up to and above the 55% toxicity level. The other 10 chemicals (1,3
      dihydroxybenzene, curcumin, propyl gallate, p-nitrophenol, ethyl acrylate,
      eugenol, tert-butylhydroquinone, 2,4-dichlorophenol, sodium xylene sulfonate and
      phthalic anhydride) produced cytotoxicity in at least one cell type, and were
      evaluated further for MN induction in most or all of the cell types listed above.
      All these chemicals induced MN at concentrations <10mM, with levels of
      cytotoxicity below 60% (measured as the replication index) in at least one cell
      type. The rodent cell lines (V79, CHO and CHL) were consistently more susceptible
      to cytotoxicity and MN induction than p53-competent cells, and are therefore more
      susceptible to giving misleading positive results. These data suggest that a
      reduction in the frequency of misleading positive results can be achieved by
      careful selection of the mammalian cell type for genotoxicity testing.

PMID- 22138619
TI  - Accuracy assessment and screening of a dairy herd with paratuberculosis by three
      different ELISAs.
AB  - Although the culture of Mycobacterium avium subsp. paratuberculosisis is the gold
      standard for the diagnosis of paratuberculosis, this bacterium is difficult to
      grow. In contrast, serological tests like ELISAs are inexpensive, rapid, and easy
      to perform. The aims of this study were to evaluate the accuracy of three
      different ELISAs: one with the commercial antigen PPA-3, another one with L5P (a
      recently described lipopentapeptide), and a third one with an in-house antigen
      whole cell lysates (WCL) of M. avium (MAA) strain D4ER (Study 1), and to compare
      them with other tests for paratuberculosis (PTB) diagnosis (Study 2). In Study 1,
      the sensitivities of the three ELISAs tested were 74.1%, 37% and 74.1%,
      respectively, whereas their specificities were 98.9%, 100% and 100%,
      respectively. In Study 2, we compared the three above-mentioned ELISAs with the
      intradermal reaction test using Avian PPD (PPDa) and fecal culture associated
      with Ziehl-Neelsen stain and PCR tests, in a dairy herd with 4.6% of cows with
      clinical signs of PTB. The results showed that fecal samples from 14 cows (16%)
      were culture-positive and that fecal samples from nine cows (10%) were PPDa
      positive. Most of these animals (culture-positive and PPDa-positive) were
      detected as positive with any of the three ELISAs tested. Serological results
      showed that 31% of the animals were positive to ELISA-PPA-3, 17% to ELISA-L5P and
      42.5% to ELISA-WCL. The combination of these three ELISAs identified 50.6% of the
      animals as positive in the infected herd. In particular, the results show that
      the locally developed ELISA seems to be useful for identifying many infected
      animals in a herd.

PMID- 22138620
TI  - A longitudinal study of the diversity and dynamics of Mycoplasma hyopneumoniae
      infections in pig herds.
AB  - A longitudinal study was carried out to investigate the diversity and persistence
      of Mycoplasma hyopneumoniae (M. hyopneumoniae) strains in four infected pig
      herds. In each herd, 20 pigs were randomly selected and blood and/or
      bronchoalveolar lavage (BAL) fluid was collected at 6, 10, 14 and 26 weeks of
      age. In the BAL fluid, quantitative PCR and MLVA (multiple-locus variable number
      of tandem repeats (VNTR) analysis) testing were performed for detection and
      typing of M. hyopneumoniae strains, respectively. At 26 weeks of age, the
      prevalence and severity of lung lesions were recorded at slaughter (minimum 50
      pigs belonging to the same batch as the investigated pigs). The percentage of
      pigs testing positive on qPCR increased from 35% at 6 weeks to 96% at 26 weeks of
      age. With MLVA testing, positive pigs were found from 14 weeks onwards. Within
      each herd, only one distinct strain was detected, although clonal variants were
      identified in two herds. In three of the herds, the strain remained present until
      slaughter age. The percentage of pigs with Mycoplasma-like lesions ranged from
      38% to 98%, and the average pneumonia score ranged from 1.7 to 11.9,
      respectively. The present field study documented that within a herd, mainly one
      distinct M. hyopneumoniae strain was present that persisted in the same animals
      for at least 12 weeks. This implies that the immune response of the animals
      following infection is not able to rapidly clear the infection from the
      respiratory tract.

PMID- 22138621
TI  - Unusual carbon fixation gives rise to diverse polyketide extender units.
AB  - Polyketides are structurally diverse and medically important natural products
      that have various biological activities. During biosynthesis, chain elongation
      uses activated dicarboxylic acid building blocks, and their availability
      therefore limits side chain variation in polyketides. Recently, the crotonyl-CoA
      carboxylase-reductase (CCR) class of enzymes was identified in primary metabolism
      and was found to be involved in extender-unit biosynthesis of polyketides. These
      enzymes are, in theory, capable of forming dicarboxylic acids that show any side
      chain from the respective unsaturated fatty acid precursor. To our knowledge, we
      here report the first crystal structure of a CCR, the hexylmalonyl-CoA synthase
      from Streptomyces sp. JS360, in complex with its substrate. Structural analysis
      and biochemical characterization of the enzyme, including active site mutations,
      are reported. Our analysis reveals how primary metabolic CCRs can evolve to
      produce various dicarboxylic acid building blocks, setting the stage to use CCRs
      for the production of unique extender units and, consequently, altered
      polyketides.

PMID- 22138622
TI  - Data and signal processing using photochromic molecules.
AB  - Photochromes are chromophores that are reversibly isomerized between two
      metastable forms using light, or light and heat. When photochromes are covalently
      linked to other chromophores, they can act as molecular photonic analogues of
      electronic transistors. As bistable switches, they can be incorporated into the
      design of molecules capable of binary arithmetic and both combinatorial and
      sequential digital logic operations. Small ensembles of such molecules can
      perform analogue signal modulation similar to that carried out by transistor
      amplifiers. Examples of molecules that perform multiple logic functions, act as
      control elements for fluorescent reporters, and mimic natural photoregulatory
      functions are presented.

PMID- 22138623
TI  - Juvenile obesity: what is its real prevalence in Spain?

PMID- 22138624
TI  - [Thyroid metastasis of lobular breast carcinoma].

PMID- 22138625
TI  - Late diagnosis of an index case of SDH-related paraganglioma/pheochromocytoma
      syndrome.

PMID- 22138628
TI  - During the stationary growth phase, Yarrowia lipolytica prevents the
      overproduction of reactive oxygen species by activating an uncoupled
      mitochondrial respiratory pathway.
AB  - In the branched mitochondrial respiratory chain from Yarrowia lipolytica there
      are two alternative oxido-reductases that do not pump protons, namely an external
      type II NADH dehydrogenase (NDH2e) and the alternative oxidase (AOX). Direct
      electron transfer between these proteins is not coupled to ATP synthesis and
      should be avoided in most physiological conditions. However, under low energy
      requiring conditions an uncoupled high rate of oxygen consumption would be
      beneficial, as it would prevent overproduction of reactive oxygen species (ROS).
      In mitochondria from high energy-requiring, logarithmic-growth phase cells, most
      NDH2e was associated to cytochrome c oxidase and electrons from NADH were
      channeled to the cytochromic pathway. In contrast, in the low energy requiring,
      late stationary-growth phase, complex IV concentration decreased, the cells
      overexpressed NDH2e and thus a large fraction of this enzyme was found in a non
      associated form. Also, the NDH2e-AOX uncoupled pathway was activated and the
      state IV external NADH-dependent production of ROS decreased.
      Association/dissociation of NDH2e to/from complex IV is proposed to be the switch
      that channels electrons from external NADH to the coupled cytochrome pathway or
      allows them to reach an uncoupled, alternative, DeltaPsi-independent pathway.

PMID- 22138627
TI  - The rate-limiting step in O(2) reduction by cytochrome ba(3) from Thermus
      thermophilus.
AB  - Cytochrome ba(3) (ba(3)) of Thermus thermophilus (T. thermophilus) is a member of
      the heme-copper oxidase family, which has a binuclear catalytic center comprised
      of a heme (heme a(3)) and a copper (Cu(B)). The heme-copper oxidases generally
      catalyze the four electron reduction of molecular oxygen in a sequence involving
      several intermediates. We have investigated the reaction of the fully reduced
      ba(3) with O(2) using stopped-flow techniques. Transient visible absorption
      spectra indicated that a fraction of the enzyme decayed to the oxidized state
      within the dead time (~1ms) of the stopped-flow instrument, while the remaining
      amount was in a reduced state that decayed slowly (k=400s(-1)) to the oxidized
      state without accumulation of detectable intermediates. Furthermore, no
      accumulation of intermediate species at 1ms was detected in time resolved
      resonance Raman measurements of the reaction. These findings suggest that O(2)
      binds rapidly to heme a(3) in one fraction of the enzyme and progresses to the
      oxidized state. In the other fraction of the enzyme, O(2) binds transiently to a
      trap, likely Cu(B), prior to its migration to heme a(3) for the oxidative
      reaction, highlighting the critical role of Cu(B) in regulating the oxygen
      reaction kinetics in the oxidase superfamily.

PMID- 22138626
TI  - Biogenesis of the cytochrome bc(1) complex and role of assembly factors.
AB  - The cytochrome bc(1) complex is an essential component of the electron transport
      chain in most prokaryotes and in eukaryotic mitochondria. The catalytic subunits
      of the complex that are responsible for its redox functions are largely conserved
      across kingdoms. In eukarya, the bc(1) complex contains supernumerary subunits in
      addition to the catalytic core, and the biogenesis of the functional bc(1)
      complex occurs as a modular assembly pathway. Individual steps of this biogenesis
      have been recently investigated and are discussed in this review with an emphasis
      on the assembly of the bc(1) complex in the model eukaryote Saccharomyces
      cerevisiae. Additionally, a number of assembly factors have been recently
      identified. Their roles in bc(1) complex biogenesis are described, with special
      emphasis on the maturation and topogenesis of the yeast Rieske iron-sulfur
      protein and its role in completing the assembly of functional bc(1) complex. This
      article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory
      Enzyme Complexes.

PMID- 22138629
TI  - Structural and functional alterations of cyanobacterial phycobilisomes induced by
      high-light stress.
AB  - Exposure of cyanobacterial or red algal cells to high light has been proposed to
      lead to excitonic decoupling of the phycobilisome antennae (PBSs) from the
      reaction centers. Here we show that excitonic decoupling of PBSs of Synechocystis
      sp. PCC 6803 is induced by strong light at wavelengths that excite either
      phycobilin or chlorophyll pigments. We further show that decoupling is generally
      followed by disassembly of the antenna complexes and/or their detachment from the
      thylakoid membrane. Based on a previously proposed mechanism, we suggest that
      local heat transients generated in the PBSs by non-radiative energy dissipation
      lead to alterations in thermo-labile elements, likely in certain rod and core
      linker polypeptides. These alterations disrupt the transfer of excitation energy
      within and from the PBSs and destabilize the antenna complexes and/or promote
      their dissociation from the reaction centers and from the thylakoid membranes.
      Possible implications of the aforementioned alterations to adaptation of
      cyanobacteria to light and other environmental stresses are discussed.

PMID- 22138631
TI  - Comparing activity analyses for improved accuracy and sensitivity of drug
      detection.
AB  - Activity (or locomotion) can be one of the most sensitive and broadly affected
      translatable biomarkers of drug or disease. However activity data often have
      variance heterogeneity and periods with zero activity, and thus is usually not
      normally distributed giving the possibility of false interpretation of the data.
      We attempt to address this issue by developing and comparing different analysis
      techniques. These include transforming the data (square root and ln) as well as
      determining the probability of activity. In order to comprehensively assess these
      analysis techniques they are applied to a variety of different activity data
      sets, which have varying pharmacological manipulation or diurnal cycle state.
      These analyses indicate that activity data can firstly be improved by a square
      root transform of the data, which reduces variance heterogeneity. A further
      improved step is to analyse the "probability of moving", which is the most
      sensitive methodology to detect a change in activity. Thus analysis of the
      powerful non-invasive physiological marker activity and locomotion can be easily
      and simply modified to improve accuracy and sensitivity in disease or drug
      detection.

PMID- 22138630
TI  - Cochlear-implant spatial selectivity with monopolar, bipolar and tripolar
      stimulation.
AB  - Sharp spatial selectivity is critical to auditory performance, particularly in
      pitch-related tasks. Most contemporary cochlear implants have employed monopolar
      stimulation that produces broad electric fields, which presumably contribute to
      poor pitch and pitch-related performance by implant users. Bipolar or tripolar
      stimulation can generate focused electric fields but requires higher current to
      reach threshold and, more interestingly, has not produced any apparent
      improvement in cochlear-implant performance. The present study addressed this
      dilemma by measuring psychophysical and physiological spatial selectivity with
      both broad and focused stimulations in the same cohort of subjects. Different
      current levels were adjusted by systematically measuring loudness growth for each
      stimulus, each stimulation mode, and in each subject. Both psychophysical and
      physiological measures showed that, although focused stimulation produced
      significantly sharper spatial tuning than monopolar stimulation, it could shift
      the tuning position or even split the tuning tips. The altered tuning with
      focused stimulation is interpreted as a result of poor electrode-to-neuron
      interface in the cochlea, and is suggested to be mainly responsible for the lack
      of consistent improvement in implant performance. A linear model could
      satisfactorily quantify the psychophysical and physiological data and derive the
      tuning width. Significant correlation was found between the individual
      physiological and psychophysical tuning widths, and the correlation was improved
      by log-linearly transforming the physiological data to predict the psychophysical
      data. Because the physiological measure took only one-tenth of the time of the
      psychophysical measure, the present model is of high clinical significance in
      terms of predicting and improving cochlear-implant performance.

PMID- 22138632
TI  - Stimulating deep cortical structures with the batwing coil: how to determine the
      intensity for transcranial magnetic stimulation using coil-cortex distance.
AB  - Transcranial magnetic stimulation (TMS) is increasingly used in cognitive
      neuroscience to probe non-motor cortical regions. A key question for such studies
      is the choice of stimulation intensity. Early studies used a simple metric such
      as 115% of motor threshold (MT) for non-motor regions; where MT is the
      stimulation intensity required to elicit a particular amplitude of motor evoked
      potential or visible muscle twitch when the coil is placed over primary motor
      cortex. Recently, however, it was demonstrated that this simple metric for
      stimulation of non-motor regions is inadequate - it could lead to over or under
      stimulation depending on the distance between the coil and the cortex. Instead, a
      method was developed to scale the motor threshold based on coil-cortex distance,
      at least for standard figure-of-eight stimulating coils. Here we validate the
      same method for a 'batwing coil', which is designed to stimulate deeper cortical
      structures such as the medial frontal cortex. We modulated coil-cortex distance
      within-participant by inserting spacers of different thickness between coil and
      scalp. We then measured MT at each spacer. We show that for every millimeter
      between coil and scalp an additional 1.4% of TMS output is required to induce an
      equivalent level of brain stimulation at the motor cortex. Using this parameter
      we describe a linear function to adjust MT for future studies of non-motor
      regions-of-interest using the batwing coil. This is the first study to
      demonstrate the effects of coil-cortical distance on stimulation efficiency via a
      monophasic system using a batwing coil.

PMID- 22138633
TI  - Nonlinear hemodynamic responses in human epilepsy: a multimodal analysis with
      fNIRS-EEG and fMRI-EEG.
AB  - Functional magnetic resonance imaging (fMRI) combined with electroencephalography
      (fMRI-EEG) is a neuroimaging technique based on the blood oxygenation level
      dependent (BOLD) signal which has been shown to be useful in the study of
      epilepsy for the localization of the epileptogenic focus. Functional near
      infrared spectroscopy (fNIRS) combined with EEG (fNIRS-EEG) is another imaging
      technique based on the measurement of oxygenated and deoxygenated hemoglobin with
      complementary clinical potential in epilepsy, for continuous patient monitoring,
      language lateralization, and focus localization. In this work fMRI-EEG and fNIRS
      EEG are used to quantify nonlinear hemodynamic responses in three cases of human
      refractory focal epilepsy, by using the Volterra kernel expansion up to second
      order. Prior to analyzing real data, extensive simulations are carried out to
      show that nonlinearities are estimable. The Volterra methodology is then applied
      to multimodal data recorded from 3 epileptic patients selected for their frequent
      spiking activity. Care is taken to account for variability of hemodynamic
      responses due to other causes than Volterra nonlinearities. Statistically
      significant nonlinearities are observed for all patients and all modalities. Good
      concordance between fNIRS and fMRI is found for both the amplitude of the
      Volterra responses, and, with limitations, in the localization of the epileptic
      focus and regions of inverted responses (negative BOLD signals). In one patient,
      Volterra nonlinearities allowed epileptic focus identification with fMRI, while
      analyses without nonlinearities failed to see it. In simulations when
      nonlinearities were included, analysis without Volterra nonlinearities performed
      poorly. These two observations suggest routinely checking for nonlinearities in
      functional imaging of patients presenting with frequent spikes.

PMID- 22138634
TI  - Structure and mechanism of a cysteine sulfinate desulfinase engineered on the
      aspartate aminotransferase scaffold.
AB  - The joint substitution of three active-site residues in Escherichia coli (L)
      aspartate aminotransferase increases the ratio of l-cysteine sulfinate
      desulfinase to transaminase activity 10(5)-fold. This change in reaction
      specificity results from combining a tyrosine-shift double mutation (Y214Q/R280Y)
      with a non-conservative substitution of a substrate-binding residue (I33Q).
      Tyr214 hydrogen bonds with O3 of the cofactor and is close to Arg374 which binds
      the alpha-carboxylate group of the substrate; Arg280 interacts with the distal
      carboxylate group of the substrate; and Ile33 is part of the hydrophobic patch
      near the entrance to the active site, presumably participating in the domain
      closure essential for the transamination reaction. In the triple-mutant enzyme,
      k(cat)' for desulfination of l-cysteine sulfinate increased to 0.5s(-1) (from
      0.05s(-1) in wild-type enzyme), whereas k(cat)' for transamination of the same
      substrate was reduced from 510s(-1) to 0.05s(-1). Similarly, k(cat)' for beta
      decarboxylation of l-aspartate increased from<0.0001s(-1) to 0.07s(-1), whereas
      k(cat)' for transamination was reduced from 530s(-1) to 0.13s(-1). l-Aspartate
      aminotransferase had thus been converted into an l-cysteine sulfinate desulfinase
      that catalyzes transamination and l-aspartate beta-decarboxylation as side
      reactions. The X-ray structures of the engineered l-cysteine sulfinate
      desulfinase in its pyridoxal-5'-phosphate and pyridoxamine-5'-phosphate form or
      liganded with a covalent coenzyme-substrate adduct identified the subtle
      structural changes that suffice for generating desulfinase activity and
      concomitantly abolishing transaminase activity toward dicarboxylic amino acids.
      Apparently, the triple mutation impairs the domain closure thus favoring
      reprotonation of alternative acceptor sites in coenzyme-substrate intermediates
      by bulk water.

PMID- 22138635
TI  - Sequence variation in couch potato and its effects on life-history traits in a
      northern malt fly, Drosophila montana.
AB  - Couch potato (cpo) has previously been connected to reproductive diapause in
      several insect species including Drosophila melanogaster, where it has been
      suggested to provide a link between the insulin signalling pathway and the
      hormonal control of diapause. In the first part of the study we sequenced nearly
      3.6 kb of this gene in a northern Drosophila species (Drosophila montana) with a
      robust photoperiodically determined diapause and found several types of
      polymorphisms along the sequenced area. We also found variation among five
      Drosophila virilis group species in the length of the 5th exon of cpo and in the
      site of the stop codon at the end of this exon. The second part of the study was
      targeted on a deletion of six amino acids located in the last section of exon 5,
      which in D. melanogaster, is translated only in one short transcript lacking the
      following exons. The studied deletion appeared to be extremely rare in the wild
      D. montana population where it was found, but its frequency rapidly increased
      during laboratory culture. qPCR analyses showed the expression level of the
      deletion allele to be significantly downregulated in both the diapausing and non
      diapausing females compared to the wild type allele. At the phenotypic level, the
      deletion and the decreased expression of cpo transcript involving it did not have
      direct effect on the incidence of female reproductive diapause, but it was
      associated with a reduction in development time under diapause-inducing
      conditions. This suggests that while the cpo transcript containing the prolonged
      version of the 5th exon with a stop codon is clearly associated with fly
      development time, the exons with RNA domains included in other transcripts of the
      gene may be more directly related to diapause regulation.

PMID- 22138637
TI  - Bioorganic synthesis, characterization and antioxidant activity of esters of
      natural phenolics and alpha-lipoic acid.
AB  - Chemo-enzymatic synthesis of six esters of natural phenolics and alpha-lipoic
      acid was carried to produce novel compounds with potential bioactivity. The
      synthetic route was mild, simple, and efficient with satisfactory yields. The
      synthesized compounds were screened for antioxidant activities. The prepared
      derivatives exhibited very good antioxidant activities as determined by DPPH
      radical scavenging assay and inhibition of lipid oxidation in fish oil emulsion
      system. Among the prepared derivatives, three compounds exhibited radical
      scavenging activity similar to the reference antioxidants, BHT and alpha
      tocopherol in the DPPH radical scavenging assay, where as in fish oil emulsion
      system, two derivatives showed activity, which was similar to the reference
      antioxidants.

PMID- 22138638
TI  - Thioredoxin 1 is responsible for antibody disulfide reduction in CHO cell
      culture.
AB  - During large-scale manufacturing of an IgG1 monoclonal antibody in Chinese
      hamster ovary (CHO) cells, reduction of the antibody's disulfide bonds was
      observed. We present evidence that mammalian thioredoxin 1 (TXN1) is the terminal
      enzyme responsible for this reduction event. We demonstrate a marked prevention
      of IgG1 disulfide bond reduction in a cell-density dependent manner by knocking
      down expression of TXN1 via lentivirus transduction of short hairpin RNA.

PMID- 22138639
TI  - Associations between the quality of the residential built environment and
      pregnancy outcomes among women in North Carolina.
AB  - BACKGROUND: The built environment, a key component of environmental health, may
      be an important contributor to health disparities, particularly for reproductive
      health outcomes. OBJECTIVE: In this study we investigated the relationship
      between seven indices of residential built environment quality and adverse
      reproductive outcomes for the City of Durham, North Carolina (USA). METHODS: We
      surveyed approximately 17,000 residential tax parcels in central Durham,
      assessing > 50 individual variables on each. These data, collected using direct
      observation, were combined with tax assessor, public safety, and U.S. Census data
      to construct seven indices representing important domains of the residential
      built environment: housing damage, property disorder, security measures, tenure
      (owner or renter occupied), vacancy, crime count, and nuisance count. Fixed-slope
      random-intercept multilevel models estimated the association between the
      residential built environment and five adverse birth outcomes. Models were
      adjusted for maternal characteristics and clustered at the primary adjacency
      community unit, defined as the index block, plus all adjacent blocks that share
      any portion of a line segment (block boundary) or vertex. RESULTS: Five built
      environment indices (housing damage, property disorder, tenure, vacancy, and
      nuisance count) were associated with each of the five outcomes in the unadjusted
      context: preterm birth, small for gestational age (SGA), low birth weight (LBW),
      continuous birth weight, and birth weight percentile for gestational age (BWPGA;
      sex-specific birth weight distributions for infants delivered at each gestational
      age using National Center for Health Statistics referent births for 2000-2004).
      However, some estimates were attenuated after adjustment. In models adjusted for
      individual-level covariates, housing damage remained statistically significantly
      associated with SGA, birth weight, and BWPGA. CONCLUSION: This work suggests a
      real and meaningful relationship between the quality of the residential built
      environment and birth outcomes, which we argue are a good measure of general
      community health.

PMID- 22138640
TI  - Outpatient treatment of primary spontaneous pneumothorax using a small-bore chest
      drain with a Heimlich valve:  the experience of a Singapore emergency department.
AB  - AIM: To review the outcomes and safety profile of small-bore (8 Fr) chest drains
      with a Heimlich valve for the treatment of primary spontaneous pneumothorax.
      METHODOLOGY: A retrospective casenotes review was carried out for pneumothorax
      cases treated with a small-bore chest drain and connected to a Heimlich valve in
      the emergency department during a 14-month period from 1 August 2009 to 30
      September 2010. Inclusion criteria were primary spontaneous pneumothorax, first
      episode, unilateral, at least 2-cm rim of air and no or minimal associated
      pleural effusion. Exclusion criterion was tension pneumothorax. Key outcomes
      studied were the success rate, as defined by sustained, complete lung re
      expansion without the need for alternative intervention (e.g. conventional chest
      tube or surgery) or admission and complication rates. RESULTS: A total of 55
      patients fulfilled the inclusion criteria and were treated with an 8 Fr chest
      tube and a Heimlich valve. The study population was predominantly (87.3%) male.
      The age range was 14-48 years (median 20). The overall success rate (as defined
      above) was 65.5% [95% confidence interval (CI): 51.4-77.8%]. The rate of surgical
      pleurodesis was 23.6% (95% CI: 13.2-37%). Complications encountered were tube
      blockage by haemoserous discharge (1.8%; 95% CI: 0-9.7%) and tube dislodgement
      (5.5%; 95% CI: 1.1-15.1%). CONCLUSION: Our results suggest that the use of a
      small-bore chest drain and a Heimlich valve is a safe and efficacious mode of
      treatment for primary spontaneous pneumothorax, which enables management of the
      majority of these patients as outpatients.

PMID- 22138641
TI  - Optetrode: a multichannel readout for optogenetic control in freely moving mice.
AB  - Recent advances in optogenetics have improved the precision with which defined
      circuit elements can be controlled optically in freely moving mammals; in
      particular, recombinase-dependent opsin viruses, used with a growing pool of
      transgenic mice expressing recombinases, allow manipulation of specific cell
      types. However, although optogenetic control has allowed neural circuits to be
      manipulated in increasingly powerful ways, combining optogenetic stimulation with
      simultaneous multichannel electrophysiological readout of isolated units in
      freely moving mice remains a challenge. We designed and validated the optetrode,
      a device that allows for colocalized multi-tetrode electrophysiological recording
      and optical stimulation in freely moving mice. Optetrode manufacture employs a
      unique optical fiber-centric coaxial design approach that yields a lightweight (2
      g), compact and robust device that is suitable for behaving mice. This low-cost
      device is easy to construct (2.5 h to build without specialized equipment). We
      found that the drive design produced stable high-quality recordings and continued
      to do so for at least 6 weeks following implantation. We validated the optetrode
      by quantifying, for the first time, the response of cells in the medial
      prefrontal cortex to local optical excitation and inhibition, probing multiple
      different genetically defined classes of cells in the mouse during open field
      exploration.

PMID- 22138642
TI  - The transmembrane LRR protein DMA-1 promotes dendrite branching and growth in C.
      elegans.
AB  - Dendrites often adopt complex branched structures. The development and
      organization of these arbors fundamentally determine the potential input and
      connectivity of a given neuron. The cell-surface receptors that control dendritic
      branching remain poorly understood. We found that, in Caenorhabditis elegans, a
      previously uncharacterized transmembrane protein containing extracellular leucine
      rich repeat (LRR) domains, which we named DMA-1 (dendrite-morphogenesis
      abnormal), promotes dendrite branching and growth. Sustained expression of dma-1
      was found only in the elaborately branched sensory neurons PVD and FLP. Genetic
      analysis revealed that the loss of dma-1 resulted in much reduced dendritic
      arbors, whereas overexpression of dma-1 resulted in excessive branching. Forced
      expression of dma-1 in neurons with simple dendrites was sufficient to promote
      ectopic branching. Worms lacking dma-1 were defective in sensing harsh touch. DMA
      1 is the first transmembrane LRR protein to be implicated in dendritic branching
      and expands the breadth of roles of LRR receptors in nervous system development.

PMID- 22138643
TI  - Cytosolic RIG-I-like helicases act as negative regulators of sterile inflammation
      in the CNS.
AB  - The action of cytosolic RIG-I-like helicases (RLHs) in the CNS during
      autoimmunity is largely unknown. Using a mouse model of multiple sclerosis, we
      found that mice lacking the RLH adaptor IPS-1 developed exacerbated disease that
      was accompanied by markedly higher inflammation, increased axonal damage and
      elevated demyelination with increased encephalitogenic immune responses.
      Furthermore, activation of RLH ligands such as 5'-triphosphate RNA
      oligonucleotides decreased CNS inflammation and improved clinical signs of
      disease. RLH stimulation repressed the maintenance and expansion of committed
      T(H)1 and T(H)17 cells, whereas T-cell differentiation was not altered. Notably,
      T(H)1 and T(H)17 suppression required type I interferon receptor engagement on
      dendritic cells, but not on macrophages or microglia. These results identify RLHs
      as negative regulators of T(H)1 and T(H)17 responses in the CNS, demonstrate a
      protective role of the RLH pathway for brain inflammation, and establish
      oligonucleotide ligands of RLHs as potential therapeutics for the treatment of
      multiple sclerosis.

PMID- 22138644
TI  - Differential control of presynaptic efficacy by postsynaptic N-cadherin and beta
      catenin.
AB  - N-cadherin is a homophilic adhesion protein that remains expressed at mature
      excitatory synapses beyond its developmental role in synapse formation. We
      investigated the trans-synaptic activity of N-cadherin in regulating synapse
      function in rodent cultured hippocampal neurons using optical methods and
      electrophysiology. Interfering with N-cadherin in postsynaptic neurons reduced
      basal release probability (p(r)) at inputs to the neuron, and this trans-synaptic
      impairment of release accompanied impaired vesicle endocytosis. Moreover, loss of
      the GluA2 AMPA-type glutamate receptor subunit, which decreased p(r) by itself,
      occluded the interference with postsynaptic N-cadherin. The loss of postsynaptic
      N-cadherin activity, however, did not affect the compensatory upregulation of
      p(r) induced by chronic activity silencing, whereas postsynaptic beta-catenin
      deletion blocked this presynaptic homeostatic adaptation. Our findings suggest
      that postsynaptic N-cadherin helps link basal pre- and postsynaptic strengths to
      control the p(r) offset, whereas the p(r) gain adjustment requires a distinct
      trans-synaptic pathway involving beta-catenin.

PMID- 22138645
TI  - alpha2-chimaerin controls neuronal migration and functioning of the cerebral
      cortex through CRMP-2.
AB  - Disrupted cortical neuronal migration is associated with epileptic seizures and
      developmental delay. However, the molecular mechanism by which disruptions of
      early cortical development result in neurological symptoms is poorly understood.
      Here we report alpha2-chimaerin as a key regulator of cortical neuronal migration
      and function. In utero suppression of alpha2-chimaerin arrested neuronal
      migration at the multipolar stage, leading to accumulation of ectopic neurons in
      the subcortical region. Mice with such migration defects showed an imbalance
      between excitation and inhibition in local cortical circuitry and greater
      susceptibility to convulsant-induced seizures. We further show that alpha2
      chimaerin regulates bipolar transition and neuronal migration through modulating
      the activity of CRMP-2, a microtubule-associated protein. These findings
      establish a new alpha2-chimaerin-dependent mechanism underlying neuronal
      migration and proper functioning of the cerebral cortex and provide insights into
      the pathogenesis of seizure-related neurodevelopmental disorders.

PMID- 22138648
TI  - Induction of excitatory and inhibitory presynaptic differentiation by GluD1.
AB  - The delta subfamily of ionotropic glutamate receptor subunits consists of GluD1
      and GluD2. GluD2, which is selectively expressed in cerebellar Purkinje neurons,
      has been shown to contribute to the formation of synapses between granule neurons
      and Purkinje neurons through interaction with Cbln1 (cerebellin precursor
      protein1) and presynaptic Neurexin. On the other hand, the synaptogenic activity
      of GluD1, which is expressed not in the cerebellum but in the hippocampus,
      remains to be characterized. Here, we report that GluD1 expressed in non-neuronal
      HEK cells, induced presynaptic differentiation of granule neurons through its N
      terminal domain in co-cultures with cerebellar neurons, similarly to GluD2. We
      also show that GluD1 rescued the defect of synapse formation in GluD2-knockout
      Purkinje neurons, indicating the functional similarity of GluD1 and GluD2. In
      contrast, GluD1 expression alone did not induce presynaptic differentiation in co
      cultures of HEK cells with hippocampal neurons. However, when Cbln1 was
      exogenously added to the culture medium, GluD1 induced presynaptic
      differentiation of not only glutamatergic presynaptic terminals but also
      GABAergic ones. Cbln1 is not expressed in hippocampal neurons but is expressed in
      entorhinal cortical neurons projecting to the hippocampus. In co-cultures of HEK
      cells expressing GluD1 and entorhinal cortical neurons, both glutamatergic and
      GABAergic presynaptic terminals were formed on the HEK cells without exogenous
      application of Cbln1. These results suggest that GluD1 might contribute to the
      formation of specific synapses in the hippocampus such as those formed by the
      projecting neurons of the entorhinal cortex.

PMID- 22138646
TI  - How the 'slow' Ca(2+) buffer parvalbumin affects transmitter release in
      nanodomain-coupling regimes.
AB  - Parvalbumin is thought to act in a manner similar to EGTA, but how a slow Ca(2+)
      buffer affects nanodomain-coupling regimes at GABAergic synapses is unclear.
      Direct measurements of parvalbumin concentration and paired recordings in rodent
      hippocampus and cerebellum revealed that parvalbumin affects synaptic dynamics
      only when expressed at high levels. Modeling suggests that, in high
      concentrations, parvalbumin may exert BAPTA-like effects, modulating nanodomain
      coupling via competition with local saturation of endogenous fixed buffers.

PMID- 22138649
TI  - mHERC6 is the essential ISG15 E3 ligase in the murine system.
AB  - Posttranslational protein modification by ubiquitin and ubiquitin-like modifiers
      (UBLs) is mediated by a hierarchical cascade of conjugating enzymes and affects
      multiple biological processes within the cell. Interferon-stimulated gene 15
      (ISG15) is an UBL, which is strongly induced by type I Interferon and ISG15
      modification was shown to play an essential role in antiviral defense. While
      hHERC5 is the major E3 ligase for ISG15 modification in humans, ISGylation in the
      murine systems at the level of E3 ligases was weakly characterized as rodent
      genomes lack a direct homologue of hHERC5. Here, we show that mHERC6 is strongly
      induced by different pathogen-associated molecular patterns (PAMPs) in a type I
      Interferon receptor (IFNAR1) dependent manner. We demonstrate that mHERC6 is
      essential for endogenous murine ISGylation and thus represents the dominant ISG15
      E3 ligase in mice. In contrast to its human homologue, mHERC6 is also capable to
      mediate conjugation of human ISG15.

PMID- 22138647
TI  - miR-124 acts through CoREST to control onset of Sema3A sensitivity in navigating
      retinal growth cones.
AB  - During axon pathfinding, growth cones commonly show changes in sensitivity to
      guidance cues that follow a cell-intrinsic timetable. The cellular timer
      mechanisms that regulate such changes are, however, poorly understood. Here we
      have investigated microRNAs (miRNAs) in the timing control of sensitivity to the
      semaphorin Sema3A in Xenopus laevis retinal ganglion cell (RGC) growth cones. A
      developmental profiling screen identified miR-124 as a candidate timer. Loss of
      miR-124 delayed the onset of Sema3A sensitivity and concomitant neuropilin-1
      (NRP1) receptor expression and caused cell-autonomous pathfinding errors. CoREST,
      a cofactor of a NRP1 repressor, was newly identified as a target and mediator of
      miR-124 for this highly specific temporal aspect of RGC growth cone
      responsiveness. Our findings indicate that miR-124 is important in regulating the
      intrinsic temporal changes in RGC growth cone sensitivity and suggest that miRNAs
      may act broadly as linear timers in vertebrate neuronal development.

PMID- 22138650
TI  - Metformin prevents endoplasmic reticulum stress-induced apoptosis through AMPK
      PI3K-c-Jun NH2 pathway.
AB  - Type 2 diabetes mellitus is thought to be partially associated with endoplasmic
      reticulum (ER) stress toxicity on pancreatic beta cells and the result of
      decreased insulin synthesis and secretion. In this study, we showed that a well
      known insulin sensitizer, metformin, directly protects against dysfunction and
      death of ER stress-induced NIT-1 cells (a mouse pancreatic beta cell line) via
      AMP-activated protein kinase (AMPK) and phosphatidylinositol-3 (PI3) kinase
      activation. We also showed that exposure of NIT-1 cells to metformin (5mM)
      increases cellular resistance against ER stress-induced NIT-1 cell dysfunction
      and death. AMPK and PI3 kinase inhibitors abolished the effect of metformin on
      cell function and death. Metformin-mediated protective effects on ER stress
      induced apoptosis were not a result of an unfolded protein response or the
      induced inhibitors of apoptotic proteins. In addition, we showed that exposure of
      ER stressed-induced NIT-1 cells to metformin decreases the phosphorylation of c
      Jun NH(2) terminal kinase (JNK). These data suggest that metformin is an
      important determinant of ER stress-induced apoptosis in NIT-1 cells and may have
      implications for ER stress-mediated pancreatic beta cell destruction via
      regulation of the AMPK-PI3 kinase-JNK pathway.

PMID- 22138651
TI  - Glycosylphosphatidylinositol (GPI)-anchoring of mamba toxins enables cell
      restricted receptor silencing.
AB  - Muscarinic toxins (MTs) are snake venom peptides found to selectively target
      specific subtypes of G-protein-coupled receptors. In here, we have attached a
      glycosylphosphatidylinositol (GPI) tail to three different toxin molecules and
      evaluated their receptor-blocking effects in a heterologous expression system.
      MT7-GPI remained anchored to the cell surface and selectively inhibited M(1)
      muscarinic receptor signaling expressed in the same cell. To further demonstrate
      the utility of the GPI tail, we generated MT3- and MTalpha-like gene sequences
      and fused these to the signal sequence for GPI attachment. Functional assessment
      of these membrane-anchored toxins on coexpressed target receptors indicated a
      prominent antagonistic effect. In ligand binding experiments the GPI-anchored
      toxins were found to exhibit similar selection profiles among receptor subtypes
      as the soluble toxins. The results indicate that GPI attachment of MTs and
      related receptor toxins could be used to assess the role of receptor subtypes in
      specific organs or even cells in vivo by transgenic approaches.

PMID- 22138652
TI  - A checkpoint in B-lymphopoiesis related to Notch resistance.
AB  - While murine B- and T-lymphopoiesis require overlapping molecules, they occur in
      separate organs: the bone marrow (BM) and the thymus, respectively. The BM
      microenvironment is incapable of supporting T-lymphopoiesis because of
      insufficient interactions of Notch1 with delta-like ligand (Dll). Notch1/Dll
      interactions also play a role in the suppression of B-lymphopoiesis in the
      thymus. However, it is still unclear whether the Notch1/Dll interaction alone
      explains why the thymus does not support B-lymphopoiesis. In this study, we
      compared the precursor population colonizing the thymus with that in the BM by
      culturing them on stromal cells expressing abundant Dll1. We demonstrated that
      Flt3(+) Il7r(+) B220(+) Cd19(+) BM cells gave rise to B cells under this
      condition. We defined them as resistant to Dll1. In the thymus, Dll1-resistant
      cells were undetectable. This suggested that the absence of Dll1-resistant cells
      might explain the absence of B-lymphopoiesis in the thymus.

PMID- 22138653
TI  - Zinc-mediated modulation of the configuration and activity of complexes between
      copper and amyloid-beta peptides.
AB  - A growing body of Alzheimer's disease (AD) research is concerned with
      understanding the interaction between amyloid-beta (Abeta) peptides and metal
      ions (e.g., Cu, Zn, and Fe) and determining the biological relevance of the metal
      Abeta complexes to essential metal homeostasis and neuronal cell loss.
      Previously, many studies have dealt with the interaction between Abeta and
      "single" but not "multiple" metal ions in terms of binding affinity and
      coordination chemistry. In the present work, we found that Zn(II) ions modified
      the configuration of Abeta-Cu(II) by forming Zn(II)-Abeta-Cu(II) ternary
      complexes. As a result, the catalytic activity of Abeta-Cu(II) against a
      biological ascorbic acid species was repressed by Zn(II) binding. The formation
      of the ternary complex can therefore explain the protective role of Zn(II) in AD.

PMID- 22138654
TI  - Epididymo-orchitis: an unusual manifestation of salmonellosis.
AB  - Salmonellosis continues to be a major public health problem, especially in
      developing countries. The formation of focal abscesses may occur following either
      hematogenous or lymphatic spread. There are large number of serious and life
      threatening clinical manifestations of Salmonella spp., ranging from
      osteomyelitis to infective endocarditis and meningitis. However, even though
      Salmonella epidydimo-orchitis is a relatively rare clinical manifestion, it can
      present, most often in male babies and adolescent boys, following contact with
      nontyphoidal Salmonella. Here, we report a case of epididymo-orchitis due to
      Salmonella Paratyphi A that presented in an otherwise healthy 63-year-old man in
      order to highlight this organism's unusual clinical presentation. In countries
      such as India, where Salmonella infections are endemic, a high index of suspicion
      should be always be maintained and the possibility of a Salmonella infection at
      an aberrant site where it is hardly expected should not be ruled out.

PMID- 22138655
TI  - Clinical and bacteriological characteristics of Klebsiella pneumoniae causing
      liver abscess with less frequently observed multi-locus sequences type, ST163,
      from Singapore and Missouri, US.
AB  - BACKGROUND: Klebsiella pneumoniae is the major cause of liver abscesses in
      several Asian countries. Differences in the type of circulating Klebsiella
      strains and/or the genetic make up of the host seem to be plausible explanations
      for this. METHODS: Two recent K. pneumoniae strains isolated from patients with
      liver abscess, one from Missouri in the US, and a second one from Singapore, were
      fully characterized by molecular typing, association of virulent genes,
      neutrophil phagocytosis, susceptibility to serum killing, and lethality in mice.
      RESULTS: Both strains had mucoid colony morphology and were similar in multilocus
      sequence type (ST-163), drug-susceptibility profile, resistance to phagocytosis
      and susceptibility to serum killing. Although ST-163 is a single nucleotide
      variant (SNV) to the major ST-23, which is specific to serotype K1 K. pneumoniae
      that causes liver abscess in Taiwan, these two isolates differ in capsular
      serotype. One was serotype K1 and the other K29. Since a serotype K35 with ST163
      was reported previously to cause peritonitis, serotype K29 with SNV to ST-23 was
      not impossible. Pulsed field gel electrophoresis by XbaI digestion showed
      different restriction patterns. The virulence-associated genes rmpA and
      aerobactin were only present in the serotype K1 isolate from Singapore and not in
      the serotype K29 isolate from Missouri. The serotype K1 isolate was also more
      virulent to mice. CONCLUSION: The reasons underlying the high prevalence of ST-23
      or its SNV in K. pueumonaie liver abscesses is worth further investigation.

PMID- 22138657
TI  - Gypsum fibrosum and its major component CaSO4 increase cutaneous aquaporin-3
      expression levels.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: We have previously reported that Byakkokaninjinto
      improves cutaneous pruritus by increasing the expression level of aquaporin-3
      (AQP3). In this study, we examined the effect of Gypsum fibrosum (main component:
      CaSO(4)), which is the main component of Byakkokaninjinto, on the cutaneous AQP3
      expression level. MATERIALS AND METHODS: KKAy mice were given a diet containing
      0.3% Gypsum fibrosum extract, or a diet containing 0.3% CaSO(4) for 4 weeks. The
      urine volume, plasma glucose levels, cutaneous AQP3 protein expression, and the
      Ca(2+) content were measured. RESULTS: The 24-h urine volumes and the plasma
      glucose levels in the Gypsum fibrosum extract group were not significantly
      different from those in the control group. In the Gypsum fibrosum extract group,
      the cutaneous AQP3 protein levels increased significantly, by approximately 3.2
      fold, compared to the control group. The cutaneous Ca(2+) content in the control
      group was approximately 35MUg/g. In the Gypsum fibrosum extract group, the Ca(2+)
      content increased to approximately 51MUg/g, which was significant compared to the
      control group. In the CaSO(4) group, an increase in the AQP3 protein expression
      levels and Ca(2+) content were observed; the extent of these increases were
      similar to those in the Gypsum fibrosum extract group. CONCLUSIONS: The results
      of this study suggest that Gypsum fibrosum plays an important role in the
      increased levels of cutaneous AQP3 expression enhanced by Byakkokaninjinto. The
      results also indicate that the increase in AQP3 caused by Gypsum fibrosum is
      attributable to an increase in the cutaneous Ca(2+) content from its main
      component, CaSO(4).

PMID- 22138658
TI  - Protective effects of Eucommia lignans against hypertensive renal injury by
      inhibiting expression of aldose reductase.
AB  - AIM OF THE STUDY: To investigate the protective effects and the underlying
      mechanism of Eucommia lignans against hypertensive renal injury. MATERIAL AND
      METHODS: Ten-week-old Wistar Kyoto rats and age matched spontaneously
      hypertension rats were used in the study. The SHR were randomly divided into 4
      groups (n=7 for each group) and received different treatment for 16 weeks, which
      including saline, Captopril, Epalrestat and Eucommia lignans, respectively.
      System blood pressures of the rats were monitored once every 4 weeks. N-Acetyl
      beta-D-glucosaminidase (NAG) activity and the ratio of albumin and urinary
      creatinine were chosen as the indices of kidney function. Then the structure and
      renal collagen type III expression of glomerular basement membrane were observed
      by microscopy and the renal aldose reductase (AR) expression was measured by
      immunohistochemistry. In vitro, the proliferation of mesangial cells induced by
      AngII was assayed by MTT, and the mRNA expression of AR was measured by RT-real
      time PCR. RESULTS: The renal function, evaluated by NAG enzyme activity and the
      ratio of albumin to urinary creatinine, was significantly ameliorated by Eucommia
      lignans treatment. Meanwhile, Eucommia lignans decreased both the protein
      (P<0.05) and the mRNA expressed lever of AR (P<0.05). Eucommia lignans also
      decreased the high expression of collagen type III in SHR (P<0.05) and inhibited
      the proliferation of renal mesangial cells induced by AngII (P<0.05). CONCLUSION:
      Eucommia lignans have protective effects against hypertensive renal injury, and
      the protective effects may be partly due to inhibition of aldose reductase.

PMID- 22138659
TI  - Lycium barbarum polysaccharides protect mice liver from carbon tetrachloride
      induced oxidative stress and necroinflammation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum has been used as a traditional
      Chinese medicine to nourish liver, kidneys and the eyes. AIM OF THE STUDY: We
      investigated the protective mechanisms of Wolfberry, Lycium barbarum
      polysaccharides (LBP) in carbon tetrachloride (CCl(4))-induced acute liver
      injury. MATERIALS AND METHODS: Mice were intraperitoneally injected with a 50
      MUl/kg CCl(4) to induce acute hepatotoxicity (8h) and were orally fed with LBP 2
      h before the CCl(4) injection. There were six experimental groups of mice (n=7-8
      per group), namely: control mice (vehicle only; 1 mg/kg LBP or 10 mg/kg LBP),
      CCl(4)-treated mice and CCl(4)+LBP treated mice (1 mg/kg LBP or 10 mg/kg LBP).
      RESULTS: Pre-treatment with LBP effectively reduced the hepatic necrosis and the
      serum ALT level induced by CCl(4) intoxication. LBP remarkably inhibited
      cytochrome P450 2E1 expression and restored the expression levels of antioxidant
      enzymes. It also decreased the level of nitric oxide metabolism and lipid
      peroxidation induced by CCl(4). LBP attenuated hepatic inflammation via down
      regulation of proinflammatory mediators and chemokines. Furthermore, LBP promoted
      liver regeneration after CCl(4) treatment. The protective effects of LBP against
      hepatotoxicity were partly through the down-regulation of nuclear factor kappa-B
      activity. CONCLUSION: LBP is effective in reducing necroinflammation and
      oxidative stress induced by a chemical toxin, thus it has a great potential use
      as a food supplement in the prevention of hepatic diseases.

PMID- 22138660
TI  - Angiogenic efficacy of simplified 2-herb formula (NF3) in zebrafish embryos in
      vivo and rat aortic ring in vitro.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic foot ulceration results in high risk of
      lower extremity amputation, and represents a significant health care expenditure
      worldwide. Radix Astragali (RA) and Radix Rehmanniae (RR) are widely used Chinese
      medicinal herbs in treating diabetes, and have shown positive effects in
      enhancing wound healing in diabetic foot ulcer animal model. MATERIALS AND
      METHODS: The angiogenic efficacy of NF3, a simplified 2-herb formula consisting
      of RA and RR in 2:1 ratio, was investigated. Median lethal concentration (LC50)
      and median effective concentration (EC50) were determined by treating zebrafish
      embryos with different concentrations of NF3 from 20 hpf to 72 hpf. The
      angiogenic activity of NF3 was examined in zebrafish embryos in vivo and by rat
      aortic ring assay in vitro. Cell cycle analysis of endothelial cells induced by
      NF3 was analyzed by flow cytometry using transgenic zebrafish Tg(fli1:EGFP). Real
      time PCR was used to analyze mRNA expression profiles of selected genes involved
      in VEGF, FGF and MAPK pathways. RESULTS: NF3 enhanced blood vessel formation as
      indicated by extra growth of intersegmental vessels in zebrafish embryos, and
      increased microvessels formation in rat aortic ring. NF3 also enhanced
      endothelial cells proliferation as shown by increased percentage of cells
      accumulating in S phase and G2/M phase of the cell cycle. NF3 exposure
      significantly induced up-regulation of VEGF-A, Flk-1, fgf1 and bRaf expression in
      zebrafish embryos. CONCLUSIONS: Our results demonstrated that NF3 was effective
      in promoting angiogenesis in zebrafish embryos and by rat aortic ring assay,
      which provided scientific basis to support the use of NF3 as potential
      therapeutics in treating diabetic foot ulceration.

PMID- 22138665
TI  - A ternary supramolecular system containing a boronated DNA-metallointercalator,
      beta-cyclodextrin and the hexanucleotide d(GTCGAC)2.
AB  - Solution NMR studies of the interaction between the hexanucleotide d(GTCGAC)(2),
      beta-cyclodextrin and a boronated 2,2':6',2''-terpyridineplatinum(II) complex
      containing 1,12-dicarba-closo-dodecaborane(12) (1,12-closo-carborane) reveal the
      formation of a remarkable ternary supramolecular system in which the terpyridine
      ligand is intercalated between the C(3) and G(4) bases, whilst the closo
      carborane moiety is encapsulated by the cyclic sugar.

PMID- 22138666
TI  - Arsenic exposure and hypertension: a systematic review.
AB  - BACKGROUND: Environmental exposure to arsenic has been linked to hypertension in
      persons living in arsenic-endemic areas. OBJECTIVE: We summarized published
      epidemiologic studies concerning arsenic exposure and hypertension or blood
      pressure (BP) measurements to evaluate the potential relationship. DATA SOURCES
      AND EXTRACTION: We searched PubMed, Embase, and TOXLINE and applied predetermined
      exclusion criteria. We identified 11 cross-sectional studies from which we
      abstracted or derived measures of association and calculated pooled odds ratios
      (ORs) using inverse-variance weighted random-effects models. DATA SYNTHESIS: The
      pooled OR for hypertension comparing the highest and lowest arsenic exposure
      categories was 1.27 [95% confidence interval (CI): 1.09, 1.47; p-value for
      heterogeneity = 0.001; I(2) = 70.2%]. In populations with moderate to high
      arsenic concentrations in drinking water, the pooled OR was 1.15 (95% CI: 0.96,
      1.37; p-value for heterogeneity = 0.002; I(2) = 76.6%) and 2.57 (95% CI: 1.56,
      4.24; p-value for heterogeneity = 0.13; I(2) = 46.6%) before and after excluding
      an influential study, respectively. The corresponding pooled OR in populations
      with low arsenic concentrations in drinking water was 1.56 (95% CI: 1.21, 2.01; p
      value for heterogeneity = 0.27; I(2) = 24.6%). A dose-response assessment
      including six studies with available data showed an increasing trend in the odds
      of hypertension with increasing arsenic exposure. Few studies have evaluated
      changes in systolic and diastolic BP (SBP and DBP, respectively) measurements by
      arsenic exposure levels, and those studies reported inconclusive findings.
      CONCLUSION: In this systematic review we identified an association between
      arsenic and the prevalence of hypertension. Interpreting a causal effect of
      environmental arsenic on hypertension is limited by the small number of studies,
      the presence of influential studies, and the absence of prospective evidence.
      Additional evidence is needed to evaluate the dose-response relationship between
      environmental arsenic exposure and hypertension.

PMID- 22138667
TI  - Startle decreases reaction time to active inhibition.
AB  - In reaction time (RT) tasks where fast ballistic movements are required, the
      requisite action is generally preplanned to enable the quickest responses. When a
      loud acoustic stimulus (e.g., >120 dB) that elicits a startle response is
      presented during the preplanning phase, the movement is triggered involuntarily
      and at a sufficiently short enough latency to discount normal cortical initiation
      processes. It has been suggested that the startle triggers the action by
      providing sufficient additional activation to surpass the initiation threshold.
      It is unclear, however, whether similar RT shortening due to startle would occur
      in the absence of an excitatory motor output. Thus, in the current study,
      participants performed a flexion force offset (i.e., inhibition) task within a
      simple RT paradigm. A startling acoustic stimulus (SAS) was presented in place of
      the usual "go" signal on several trials. Results from startle trials showed that
      the inhibitory command could be elicited substantially earlier by an SAS (latency
      of ~78 ms) compared to control trials (120 ms). This suggests active inhibition
      is preprogrammed and can be triggered early by startle in similar way to
      traditional "excitatory" tasks. Additionally, early startle-related EMG activity
      superimposed with the triggered offset suggests that the nature of the inhibitory
      command used in the current experiment involves the active suppression of ongoing
      motor output.

PMID- 22138668
TI  - Expression and correlation of Lewis y antigen and TGF-beta1 in ovarian epithelial
      carcinoma.
AB  - Lewis y is a difucosylated oligosaccharide carried by glycoconjugates on the cell
      surface. Elevation of Lewis y is frequently observed in epithelial-derived
      cancers. This study aimed to detect the expression and clinical significance of
      the Lewis y antigen and TGF-beta1 (transforming growth factor beta1) in ovarian
      epithelial tumors, and to evaluate the correlation between them.
      Immunohistochemical staining was used to detect the expression of Lewis y antigen
      and TGF-beta1 in 60 cases of ovarian epithelial malignant tumors, 20 cases of
      borderline ovary tumors, 20 cases of benign ovary tumors and 10 cases of normal
      ovarian tissues. An immunofluorescence double labeling method was also used to
      detect the correlation between Lewis y antigen and TGF-beta1. The positive rates
      of Lewis y antigen in ovarian epithelial cancer tissues was 88.33%, significantly
      higher compared to those of borderline ovarian tumors (60.00%) (P<0.05), benign
      ovarian tumors (35.00%) (P<0.01) and normal ovarian tissues (0%) (P<0.01). Its
      expression was not associated with clinical parameters; the positive rates of TGF
      beta1 in ovarian epithelial cancers were 78.33%, significantly higher compared to
      those of benign ovarian tumors (65.00%) (P<0.05) and normal ovarian tissues
      (40.00%) (P<0.05); the positive rates of the TGF-beta1 and Lewis y were not
      associated with metastasis of lymph nodes and histological types, differentiation
      degree and clinical stage (P>0.05). Expression of Lewis y antigen and TGF-beta1
      was significantly positively associated with epithelial carcinoma. Close
      correlation between Lewis y, TGF-beta1 and ovarian cancer was observed. Altered
      expression of Lewis y antigen may cause changes in TGF-beta1 expression. Lewis y
      can increase the growth of ovarian cancer cells and the invasion ability by
      promoting TGF-beta1 abnormal expression and by promoting angiogenesis and a
      change in its signal transduction pathway. This study provides theoretical
      evidence for the development of ovarian cancer biological treatments.

PMID- 22138669
TI  - Evaluation of genotypic prediction of HIV-1 tropism using population sequencing
      of replicates.
AB  - Determination of human immunodeficiency virus tropism has contributed to the
      understanding of the pathogenesis of HIV and is necessary prior to the use of
      CCR5 antagonists. Replicate V3 sequences may generate different sequences and
      improve viral tropism prediction. The diversity of HIV was evaluated to access
      its influence on prediction. Plasma RNA was retro-transcribed and amplified using
      a one-step protocol, followed by nested PCR and sequencing using an ABI3130XL.
      Eighty-one patients, 74% male and 26% female, with a median age of 44 years had
      either a single sequence (n=50) or 2-4 replicates (n=31) evaluated. Most patients
      (92%) had used multiple anti-retroviral regimens. Tropism prediction was
      performed using the Geno2pheno clonal option. The number of ambiguous
      nucleotides, the deduced non-synonymous amino acids at V3 and the genetic
      distance were quantified. Using a 20% false positive rate (FPR) cut-off, 41/81
      (50.6%) was predicted as X4. TCD4 was lower, 226 cells/mm(3) (IQR 82-378), in
      patients infected with X4; TCD4 for R5 was 324 cells/mm(3) (IQR 200-538, p<0.05).
      The number of ambiguous nucleotides correlated with a lower FPR value (p<0.0027).
      Although different sequences may be generated, the number of replicates was not
      associated to a lower FPR or X4 assignment, and may allow a better prediction of
      this biological characteristic. Ambiguous nucleotides correlate inversely to a
      lower FPR.

PMID- 22138671
TI  - Genetic diversity of hantaviruses in Mexico: identification of three novel
      hantaviruses from Neotominae rodents.
AB  - A variety of hantaviruses are harbored by rodents in North and South America,
      some of which can cause hantavirus pulmonary syndrome. To obtain greater
      evolutionary insight into hantaviruses in the Americas, a total of 211 rodents
      were captured in the Mexican states of Guerrero and Morelos in 2006. Anti
      hantavirus antibodies were detected in 27 of 211 serum samples (12.8%) by ELISA.
      The distribution of seropositive rodents was: 17 Peromyscus beatae, 1
      Megadontomys thomasi, 1 Neotoma picta, 6 Reithrodontomys sumichrasti, and 2
      Reithrodontomys megalotis. The hantavirus small (S), medium (M), and large (L)
      genome segments from P. beatae, R. sumichrasti, and R. megalotis were amplified
      and the sequences covering the open reading frames were determined. The
      hantaviruses from P. beatae, R. sumichrasti, and R. megalotis were provisionally
      designated Montano (MTN), Carrizal (CAR), and Huitzilac (HUI), respectively. The
      M segment amino acid identities among the Mexican hantaviruses were 80.8-93.0%.
      When these M segments were compared to those of known hantaviruses, MTN virus was
      most closely related to Limestone Canyon (LSC) virus (88.9% amino acid identity),
      while the CAR and HUI viruses were most closely related to El Moro Canyon (ELMC)
      virus (90-91% identity). Phylogenetic analysis revealed that the MTN, CAR, and
      HUI viruses occupy a monophyletic clade with the LSC, ELMC, and Rio Segundo
      viruses, which are harbored by Peromyscus boylii, R. megalotis, and
      Reithrodontomys mexicanus, respectively. The data obtained in this study provide
      important information for understanding the evolution of hantaviruses in the
      Americas.

PMID- 22138672
TI  - Inhibition of nuclear factor kappa B activation reduces Coxsackievirus B3
      replication in lymphoid cells.
AB  - Interactions between viral replication machineries and host cell metabolism
      display interesting information how certain viruses capitalize cellular pathways
      to support progeny production. Among those pathogens, Coxsackievirus B3 (CVB3)
      has been identified to manipulate intracellular signaling very comprehensively.
      Next to others, this human pathogenic virus causes acute and chronic forms of
      myocarditis, pancreatitis, and meningitis. Here, activation of nuclear factor
      kappa B (NFkappaB) signaling appears to be involved in successful infection.
      Viral replication is not restricted to solid organs but involves susceptible
      immune cells as well. In the present study, p65 phosphorylation as one aspect of
      NFkappaB activation and inhibition via BAY 11-7085 administration was analyzed in
      the context of CVB3 replication in lymphoid cells. During CVB3 infection, an up
      regulation of p65 translation is detectable, which is accompanied by noticeable
      phosphorylation. Inhibition of NFkappaB signaling reduces viral replication in a
      dose- and time-dependent manner. Taken together, these results indicate that
      during CVB3 replication in human and murine lymphoid cells, NFkappaB signaling is
      activated and facilitates viral replication. Therefore, antiviral strategies to
      target such central cellular signaling pathways may represent potential
      possibilities for the development of new virostatica.

PMID- 22138673
TI  - High-field MRI and powerdoppler sonography: supplementary imaging, techniques in
      assessing disease activity in patients with psoriasis arthritis (PsA) and
      rheumatoid arthritis (RA) receiving adalimumab.

PMID- 22138674
TI  - Genetic polymorphisms of the DNA repair gene UNG are associated with the
      susceptibility of rheumatoid arthritis.
AB  - The involvement of uracil-DNA glycosylase (UNG) in the pathogenesis of cancer is
      well documented. In contrast, the role of this protein in rheumatoid arthritis
      (RA) development is not well defined, although previous studies suggest a
      possible link between autoimmune diseases and malignancy. Therefore, we aimed to
      examine whether there is a link between UNG genetic polymorphisms and RA. Our
      present study investigated the effects of UNG (rs3219218 and rs246079) single
      nucleotide polymorphisms (SNPs) on RA among Taiwan's Han Chinese population.
      Polymorphism of the UNG gene was analyzed in 192 controls and 183 RA patients.
      Genotyping for UNG SNPs was performed by restriction fragment length polymorphism
      assay. Our data confirmed statistically significant variations in genotype
      frequency distributions at rs246079 SNP between RA patients and controls (P =
      3.05 * 10(-4)). The G allele at rs246079 SNP is a high-risk factor in developing
      RA (odds ratio [OR] = 1.77; 95% confidence interval [CI] = 1.290-2.42). A
      comparison of haplotype frequencies between the case and the control revealed
      that RA patients with the Ht2 haplotype are at additional risk for RA development
      (P = 0.042). Our data yielded new information on UNG polymorphisms associated
      with RA development and as RA molecular markers. The polymorphisms revealed by
      the present study merit further investigation.

PMID- 22138675
TI  - Aeromonas diarrhea and Behcet's disease: more than a mere association.

PMID- 22138677
TI  - A 17-year-old male with nephrotic syndrome and diffuse adenopathy: questions.

PMID- 22138679
TI  - Homogeneously mixed porphyrin J-aggregates with rod-shaped nanostructures via
      zwitterionic self-assembly.
AB  - To tailor functional nanomaterials, the co-assembly of self-assembling dyes in a
      homogeneous way would be a promising approach because the electronic properties
      can be tuned by the mixing ratio. Although porphyrins are important
      supramolecular building blocks with unique optical properties, a homogeneously
      mixed J-aggregate system of porphyrins has not been reported yet. Herein, we
      focused on three kinds of zwitterionic porphyrin diacids, H(4)TSPP(2-), H(4)T(5
      STh)P(2-) and H(4)T(4-STh)P(2-), due to their capability to form J-aggregates
      with distinguished optical properties and well-defined nanostructures. In this
      study, we investigated the co-assembly behaviours of the zwitterionic porphyrins
      in aqueous solution by UV-vis and RLS, and investigated the morphology of the
      resultant homogeneously mixed J-aggregates by AFM. In the case of the combination
      of H(4)TSPP(2-) and H(4)T(5-STh)P(2-), they readily co-assemble to form
      homogeneously mixed J-aggregates with different types of binary excitonic bands,
      whereas the combination of H(4)T(4-STh)P(2-) and other porphyrins results in the
      dominant formation of the individual pure J-aggregates. Deposited homogeneously
      mixed J-aggregates of H(4)TSPP(2-) with H(4)T(5-STh)P(2-) consist of rod-shaped
      nanostructures, whose height changes discontinuously upon varying the mixing
      ratio. These results would provide new insights into the electronic properties
      and the nanostructure of self-assembled multicomponent materials.

PMID- 22138676
TI  - PAX2 in human kidney malformations and disease.
AB  - Human PAX2 mutations have been associated with abnormalities in the developing
      and adult kidney ranging from congenital abnormalities of the kidney and urinary
      tract (CAKUT) to oncogenic processes. Defining the relationship of PAX2 to human
      renal disease requires an appreciation of its fundamental role in renal
      development. Given the highly conserved nature of the PAX2 gene in vertebrates,
      it is not surprising that much of our understanding of PAX2 involvement in renal
      disease has been derived from animal models. The following review will outline
      the current evidence supporting involvement of PAX2 in the pathologic processes
      involving the kidney.

PMID- 22138680
TI  - Disseminated cryptococcal infection in patient with novel JAK3 mutation severe
      combined immunodeficiency, with resolution after stem cell transplantation.
AB  - Disseminated cryptococcal infection is the second most common cause of death
      after tuberculosis in acquired immune deficiency syndrome patients. Surprisingly,
      it has been reported only in few patients with primary immunodeficiency diseases.
      Herein, we report the clinical presentation and outcome of a 23-month-old boy
      with novel JAK3 mutation severe combined immunodeficiency disease complicated by
      severe disseminated cryptococcal infection.

PMID- 22138681
TI  - A validated method for quantitation of psilocin in plasma by LC-MS/MS and study
      of stability.
AB  - A liquid chromatography-electrospray ionization/tandem mass spectrometry method
      for the quantitation of psilocin in plasma is presented. Sample workup was
      performed with mixed-mode solid-phase extraction using ascorbic acid and nitrogen
      for drying to protect the unstable analyte. Calibration curves were linear from 2
      to 100 ng/mL, and no selectivity problems occurred. The limit of detection was
      0.1 ng/mL, and the limit of quantitation was 0.34 ng/mL. Recovery was >86% and
      matrix effects were <110%. Both were reproducible. Interday and intraday
      precisions at different concentrations were 1.5-4.3% relative standard deviation,
      bias within +/-9%. Processed samples were stable in the autosampler for at least
      26 h. Furthermore, the stability of psilocin in blood stored at different
      temperatures over various periods of time was investigated. Samples stored at
      room temperature showed a continuous decrease of analyte leading to a loss of
      about 90% after 1 week. Storage in the fridge improved sample stability
      significantly. Freezing of blood samples led to a not reproducible loss of
      psilocin.

PMID- 22138682
TI  - Validation of a high-throughput real-time polymerase chain reaction assay for the
      detection of capripoxviral DNA.
AB  - Capripoxviruses, which are endemic in much of Africa and Asia, are the
      aetiological agents of economically devastating poxviral diseases in cattle,
      sheep and goats. The aim of this study was to validate a high-throughput real
      time PCR assay for routine diagnostic use in a capripoxvirus reference
      laboratory. The performance of two previously published real-time PCR methods
      were compared using commercially available reagents including the amplification
      kits recommended in the original publication. Furthermore, both manual and
      robotic extraction methods used to prepare template nucleic acid were evaluated
      using samples collected from experimentally infected animals. The optimised assay
      had an analytical sensitivity of at least 63 target DNA copies per reaction,
      displayed a greater diagnostic sensitivity compared to conventional gel-based
      PCR, detected capripoxviruses isolated from outbreaks around the world and did
      not amplify DNA from related viruses in the genera Orthopoxvirus or Parapoxvirus.
      The high-throughput robotic DNA extraction procedure did not adversely affect the
      sensitivity of the assay compared to manual preparation of PCR templates. This
      laboratory-based assay provides a rapid and robust method to detect
      capripoxviruses following suspicion of disease in endemic or disease-free
      countries.

PMID- 22138683
TI  - Inhibition of porcine hemagglutinating encephalomyelitis virus replication by
      short hairpin RNAs targeting of the nucleocapsid gene in a porcine kidney cell
      line.
AB  - Porcine hemagglutinating encephalomyelitis virus (PHEV), which causes porcine
      encephalomyelitis and is widespread among swine worldwide. RNA interference
      (RNAi) pathways have emerged as important regulators of virus-host cell
      interactions. In this study, two siRNA expression plasmids (shN1 and shN2) were
      generated to target two different coding regions of the nucleocapsid protein (N)
      of PHEV. The shRNAs were transiently transfected into a porcine kidney cell line,
      PK-15, to determine whether these constructs inhibited PHEV production. Our
      results revealed that both shRNAs were highly capable of inhibiting viral RNA
      genome replication, especially shN2. Next, stable transfection of shN2 was used
      to produce two siRNA stably expressing PK-15 cell clones (shN2-1 and shN2-2), and
      these two lines were infected with PHEV. The analysis of cytopathic effects (CPE)
      demonstrated that shN2-1 and shN2-2 were capable of protecting cells against PHEV
      infection with high specificity and efficiency. Furthermore, effective inhibition
      of viral replication persisted for up to 120 h by a TCID(50) assay. These results
      indicated that RNAi targeting of the N gene could facilitate studies of the
      specific function of viral genes associated with PHEV replication and may have
      potential therapeutic applications.

PMID- 22138684
TI  - Illness experience in patients with hepatocellular carcinoma:  an interpretative
      phenomenological analysis study.
AB  - AIMS: Hepatocellular carcinoma (HCC) is common in Asia and has implications for
      compromised health-related quality of life. We report a qualitative study to
      explore the impact of HCC on patients' lives and the adjustment process. METHODS:
      Thirty-three adult patients with HCC in Taiwan (age from 31 to 76 years) took
      part in a semistructured interview. The interview guide included illness
      experience, strategies used to deal with the disease, and any significant
      concerns in their current life. Data were analyzed using interpretative
      phenomenological analysis. RESULTS: Three main themes were identified. These
      included: (a) the impact of disease: HCC was associated with physical symptoms
      and psychosocial stress, as well as positive changes; (b) illness perceptions:
      patients perceived HCC as a long-term and chronic disease that could not be cured
      but might be controlled; and (c) coping strategies: these included focusing on
      managing HCC and its symptoms, emotional responses, and leading a normal life.
      CONCLUSION: Patients' physical condition, their illness perceptions, and coping
      strategies all contributed to their disease adjustment. Our results suggest that
      patients in Taiwan are as keen for information about their disease as described
      in Western cultures. Cross-cultural work is needed to enhance our understanding
      about how the social or cultural contexts shape individuals coping with cancer.

PMID- 22138685
TI  - Do outcomes of arterial embolization for acute gastrointestinal bleeding depend
      on the choice of embolic agent?

PMID- 22138686
TI  - Absolute CD4 counts in monoinfected chronic hepatitis B patients in the advanced
      immune-active stage.

PMID- 22138687
TI  - Iris neovascularization and neovascular glaucoma in neurofibromatosis type 1:
      report of 3 cases in children.
AB  - PURPOSE: To report the clinical findings and outcomes in 3 patients with
      neurofibromatosis 1 (NF1) and retinal vascular abnormalities that resulted in
      angle closure secondary to iris neovascularization and describe the
      histopathologic abnormalities in 1 case. PATIENTS AND METHODS: Retrospective case
      series of patients with NF1 and angle closure due to iris neovascularization
      secondary to retinal vascular abnormalities. Histopathologic analysis of an
      enucleated eye in 1 case. RESULTS: Three children whose age ranged from 5 to 10
      years at presentation, developed unilateral retinal vascular abnormalities that
      resulted in iris neovascularization and angle closure with a wide range of
      intraocular pressures. Two patients had retinal vasoproliferative lesions of
      which the affected eye became blind in 1 patient and the other retained useful
      vision after treatment with intracameral Bevacizumab, ablation of the retinal
      lesions, and surgical treatment of the neovascular glaucoma. The third patient
      underwent enucleation and had pathologic evidence of retinal ischemia.
      CONCLUSIONS: A variety of retinal vascular lesions occurring in NF1 are capable
      of producing iris neovascularization, ectropion uvea, and neovascular glaucoma.
      Although a spectrum of serious complications resulting in total vision loss can
      occur, retention of useful vision is possible, in some cases, with aggressive
      treatment of the retinal lesions and associated neovascular glaucoma. This report
      highlights the need for careful examination of the posterior segment with special
      attention to peripheral retinal vascular abnormalities or tumors in young
      patients with NF1.

PMID- 22138688
TI  - Methods for observational post-licensure medical product safety surveillance.
AB  - Post-licensure medical product safety surveillance is important for detecting
      adverse events potentially not identified pre-licensure. Historically, post
      licensure safety monitoring has been accomplished using passive reporting systems
      and by conducting formal Phase IV randomized trials or large epidemiological
      studies, also known as safety surveillance or pharmacovigilance studies. However,
      crucial gaps in the safety evidence base provided by these approaches have led to
      high profile product withdrawals and growing public concern about unknown health
      risks associated with licensed products. To address the limitations of existing
      surveillance systems and to facilitate more accurate and rapid detection of
      safety problems, new systems involving active surveillance of large, population
      based cohorts using observational health care databases are being developed. In
      this article, we review common statistical methods that have been employed
      previously for post-licensure safety monitoring, including data mining and
      sequential hypothesis testing, and assess which methods may be promising for
      potential use within this newly proposed prospective observational cohort
      monitoring framework. We discuss gaps in existing approaches and identify areas
      where methodological development is needed to improve the success of safety
      surveillance efforts in this setting. 

PMID- 22138689
TI  - Large-scale discovery of enhancers from human heart tissue.
AB  - Development and function of the human heart depend on the dynamic control of
      tissue-specific gene expression by distant-acting transcriptional enhancers. To
      generate an accurate genome-wide map of human heart enhancers, we used an
      epigenomic enhancer discovery approach and identified ~6,200 candidate enhancer
      sequences directly from fetal and adult human heart tissue. Consistent with their
      predicted function, these elements were markedly enriched near genes implicated
      in heart development, function and disease. To further validate their in vivo
      enhancer activity, we tested 65 of these human sequences in a transgenic mouse
      enhancer assay and observed that 43 (66%) drove reproducible reporter gene
      expression in the heart. These results support the discovery of a genome-wide set
      of noncoding sequences highly enriched in human heart enhancers that is likely to
      facilitate downstream studies of the role of enhancers in development and
      pathological conditions of the heart.

PMID- 22138690
TI  - Genome-wide association study of flowering time and grain yield traits in a
      worldwide collection of rice germplasm.
AB  - A high-density haplotype map recently enabled a genome-wide association study
      (GWAS) in a population of indica subspecies of Chinese rice landraces. Here we
      extend this methodology to a larger and more diverse sample of 950 worldwide rice
      varieties, including the Oryza sativa indica and Oryza sativa japonica
      subspecies, to perform an additional GWAS. We identified a total of 32 new loci
      associated with flowering time and with ten grain-related traits, indicating that
      the larger sample increased the power to detect trait-associated variants using
      GWAS. To characterize various alleles and complex genetic variation, we developed
      an analytical framework for haplotype-based de novo assembly of the low-coverage
      sequencing data in rice. We identified candidate genes for 18 associated loci
      through detailed annotation. This study shows that the integrated approach of
      sequence-based GWAS and functional genome annotation has the potential to match
      complex traits to their causal polymorphisms in rice.

PMID- 22138691
TI  - Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway
      components in clear cell renal cell carcinoma.
AB  - We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and
      performed a screen of ~1,100 genes in 88 additional ccRCCs, from which we
      discovered 12 previously unidentified genes mutated at elevated frequencies in
      ccRCC. Notably, we detected frequent mutations in the ubiquitin-mediated
      proteolysis pathway (UMPP), and alterations in the UMPP were significantly
      associated with overexpression of HIF1alpha and HIF2alpha in the tumors (P = 0.01
      and 0.04, respectively). Our findings highlight the potential contribution of
      UMPP to ccRCC tumorigenesis through the activation of the hypoxia regulatory
      network.

PMID- 22138692
TI  - Genome-wide copy number variation study associates metabotropic glutamate
      receptor gene networks with attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common, heritable
      neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy
      number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children
      of European ancestry using 550,000 SNPs. We evaluated statistically significant
      findings in multiple independent cohorts, with a total of 2,493 cases with ADHD
      and 9,222 controls of European ancestry, using matched platforms. CNVs affecting
      metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 *
      10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in
      ten cases and one control (P = 1.36 * 10(-6)). We saw GRM7 deletions in six
      cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was
      duplicated in eight cases. We experimentally validated the observed variants
      using quantitative RT-PCR. A gene network analysis showed that genes interacting
      with the genes in the GRM family are enriched for CNVs in ~10% of the cases (P =
      4.38 * 10(-10)) after correction for occurrence in the controls. We identified
      rare recurrent CNVs affecting glutamatergic neurotransmission genes that were
      overrepresented in multiple ADHD cohorts.

PMID- 22138693
TI  - Dnmt3a is essential for hematopoietic stem cell differentiation.
AB  - Loss of the de novo DNA methyltransferases Dnmt3a and Dnmt3b in embryonic stem
      cells obstructs differentiation; however, the role of these enzymes in somatic
      stem cells is largely unknown. Using conditional ablation, we show that Dnmt3a
      loss progressively impairs hematopoietic stem cell (HSC) differentiation over
      serial transplantation, while simultaneously expanding HSC numbers in the bone
      marrow. Dnmt3a-null HSCs show both increased and decreased methylation at
      distinct loci, including substantial CpG island hypermethylation. Dnmt3a-null
      HSCs upregulate HSC multipotency genes and downregulate differentiation factors,
      and their progeny exhibit global hypomethylation and incomplete repression of HSC
      specific genes. These data establish Dnmt3a as a critical participant in the
      epigenetic silencing of HSC regulatory genes, thereby enabling efficient
      differentiation.

PMID- 22138695
TI  - Managing motion sickness.

PMID- 22138694
TI  - A genome-wide association study in Han Chinese identifies new susceptibility loci
      for ankylosing spondylitis.
AB  - To identify susceptibility loci for ankylosing spondylitis, we performed a two
      stage genome-wide association study in Han Chinese. In the discovery stage, we
      analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing
      spondylitis and 4,231 controls; in the validation stage, we analyzed 30
      suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls.
      We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3
      (rs4552569; P = 8.77 * 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 *
      10(-8)). We also confirmed previously reported associations in Europeans within
      the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 *
      10(-324)) and at 2p15 (rs10865331; P = 1.98 * 10(-8)). We show that rs13202464
      within the MHC region mainly represents the risk effect of HLA-B*27 variants
      (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly
      discovered loci implicate genes related to bone formation and cartilage
      development, suggesting their potential involvement in the etiology of ankylosing
      spondylitis.

PMID- 22138696
TI  - Developing countries are not making the most of TRIPS flexibilities because of
      political pressure.

PMID- 22138697
TI  - Antiretroviral therapy and the prevention of sexually transmitted HIV infection.

PMID- 22138698
TI  - Joint working in health and social care remains patchy despite years of effort.

PMID- 22138699
TI  - College urges government to rethink its proposals on commissioning support.

PMID- 22138700
TI  - Obturator hernia: the Mayo Clinic experience.
AB  - BACKGROUND: Obturator herniae (OH) are rare, with nonspecific signs and symptoms,
      and diagnosis is usually delayed until laparotomy. The added benefit of
      preoperative diagnosis with computed tomography (CT) remains unclear. METHODS: We
      reviewed the clinical characteristics and outcomes of OH repairs performed at our
      institution over a 58-year period. Outcomes were compared between patients who
      did or did not have a preoperative CT. RESULTS: Between 1950 and 2008, 30
      patients (median age 82 years, 29 women) underwent OH repair. The most common
      presenting signs and symptoms were bowel obstruction (63%), abdominal/groin pain
      (57%), and a palpable lump (10%). The pathognomonic Howship-Romberg sign was
      present in 11 patients (37%). The diagnosis was made preoperatively in nine
      patients: clinically in one (3%) and with CT in eight (27%). Nineteen patients
      (63%) presented emergently. Primary and prosthetic repair were performed in 23
      (77%) and seven (23%) patients, respectively. Small-bowel resection was performed
      in 14 patients (47%). Perioperative morbidity (30%) and mortality (10%) rates
      were high. Patients with a preoperative CT were less likely to develop a
      postoperative complication of any type [odds ratio (OR) 0.8, P = 0.04]; however,
      time to operation, length of stay, need for bowel resection, and mortality rate
      did not differ (P = NS). No recurrences were detected at a median follow-up of 2
      years (range 0-55). CONCLUSION: Although CT imaging provides an excellent means
      of preoperative diagnosis, suggestive signs and symptoms in a "skinny old lady"
      should prompt immediate operative intervention without delay.

PMID- 22138701
TI  - Comments about the article "Open tension-free Lichtenstein repair of inguinal
      hernia: use of fibrin glue versus sutures for mesh fixation" by Negro et al.

PMID- 22138702
TI  - How is reward sensitivity related to bodyweight in children?
AB  - Previous research assumes that there are two seemingly opposing hypotheses for
      the relation between reward sensitivity (RS) and bodyweight: hyper-responsiveness
      model and Reward Deficiency Syndrome (RDS), leading to the proposition of a feed
      forward process of weight gain. High RS may contribute to overeating and weight
      gain among normal weight individuals. Over time the excessive food-intake may
      evolve in a down-regulation of dopamine (RDS), resulting in overeating as a form
      of self-medication and the progression to obesity. This process was evidenced in
      adults showing a curvi-linear relationship between self-reported RS and BMI. The
      aim of the current study was to investigate the association between self-reported
      RS and BMI in children (10-15 years). The results confirm the non-linear
      relationship between RS and bodyweight and support the suggestion of the same
      feed forward process in children. These findings imply that it is crucial to
      reduce the intake of high palatable foods in high RS children to prevent the
      decrease in RS and reduce the risk for future weight gain.

PMID- 22138705
TI  - Bone erosion due to aortic prosthesis by 18F-FDG-PET/CT.

PMID- 22138703
TI  - Overt and latent cardiac effects of ozone inhalation in rats: evidence for
      autonomic modulation and increased myocardial vulnerability.
AB  - BACKGROUND: Ozone (O3) is a well-documented respiratory oxidant, but increasing
      epidemiological evidence points to extrapulmonary effects, including positive
      associations between ambient O3 concentrations and cardiovascular morbidity and
      mortality. OBJECTIVE: With preliminary reports linking O3 exposure with changes
      in heart rate (HR), we investigated the hypothesis that a single inhalation
      exposure to O3 will cause concentration-dependent autonomic modulation of cardiac
      function in rats. METHODS: Rats implanted with telemeters to monitor HR and
      cardiac electrophysiology [electrocardiography (ECG)] were exposed once by whole
      body inhalation for 4 hr to 0.2 or 0.8 ppm O3 or filtered air. A separate cohort
      was tested for vulnerability to aconitine-induced arrhythmia 24 hr after
      exposure. RESULTS: Exposure to 0.8 ppm O3 caused bradycardia, PR prolongation, ST
      depression, and substantial increases in atrial premature beats, sinoatrial
      block, and atrioventricular block, accompanied by concurrent increases in several
      HR variability parameters that were suggestive of increased parasympathetic tone.
      Low-O3 exposure failed to elicit any overt changes in autonomic tone, heart
      rhythm, or ECG. However, both 0.2 and 0.8 ppm O3 increased sensitivity to
      aconitine-induced arrhythmia formation, suggesting a latent O3-induced alteration
      in myocardial excitability. CONCLUSIONS: O3 exposure causes several alterations
      in cardiac electrophysiology that are likely mediated by modulation of autonomic
      input to the heart. Moreover, exposure to low O3 concentrations may cause
      subclinical effects that manifest only when triggered by a stressor, suggesting
      that the adverse health effects of ambient levels of air pollutants may be
      insidious and potentially underestimated.

PMID- 22138706
TI  - Unexpected only pulmonary manifestation of sarcoidosis.

PMID- 22138707
TI  - 18F-FDG-PET/CT in myelofibrosis.

PMID- 22138708
TI  - Inhibition or deficiency of cathepsin B leads defects in HIV-1 Gag pseudoparticle
      release in macrophages and HEK293T cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) egresses from infected cells through
      utilizing the host membrane budding mechanisms. Assembly of HIV-1 Gag particles
      occurs on membranes where the Gag multimers subsequently bud off and form
      enveloped viral particles. In certain cell types such as macrophages, HIV-1 Gag
      particles have shown to be released into intracellular virus containing
      compartments (VCC) such as late endosomes, multivesicular bodies (MVBs) or
      invaginated plasma membrane pockets. Here, we showed that macrophages or HEK293T
      cells treated with the cathepsin B (CTSB)-specific inhibitor CA-074Me or cells
      deficient in CTSB failed to release HIV-1 Gag pseudoparticles into the
      extracellular environment. Based on immunofluorescence and electron microscopy,
      these cells retained the pseudoparticles in heterogeneous intracellular VCC. CA
      074Me was also able to inhibit propagation of two enveloped viruses, herpes
      simplex virus and influenza A virus, but not non-enveloped enterovirus. These
      results suggest that CTSB is required for the efficient release of HIV-1 Gag
      pseudoparticles and targeting CTSB can be a new therapeutic strategy for
      inhibiting egress of HIV-1 and other enveloped viruses.

PMID- 22138709
TI  - The impact of cellular debris on Pseudomonas aeruginosa adherence to silicone
      hydrogel contact lenses and contact lens storage cases.
AB  - OBJECTIVES: To evaluate neutrophil-enhanced Pseudomonas aeruginosa (PA) biofilm
      formation on silicone hydrogel contact lenses and to determine the effect of
      epithelial biodebris on PA adherence in contact lens storage cases. METHODS: A
      fully invasive PA corneal isolate stably conjugated to green fluorescent protein
      was used. Unworn lotrafilcon A contact lenses were incubated at various ratios of
      PA to polymorphonuclear neutrophil (PMN) for 24 hours at 37 degrees C. Lens
      associated PA was evaluated using laser scanning confocal microscopy and
      nonviable PA were visualized using propidium iodide. Viable bacteria were
      enumerated by colony-forming unit (CFU) analysis. For acute epithelial cell
      studies, PA viability was determined after coincubation with freeze-thaw
      epithelial cell lysates in 96-well polystyrene plates. Levels of residual
      cellular debris and bacterial viability were further assessed in used contact
      lens storage cases. RESULTS: Laser scanning confocal microscopy demonstrated that
      cotreatment with PMA-stimulated neutrophils increased PA adherence over 24 hours
      to lens surfaces with a striking alteration of PA architecture. Propidium iodide
      staining showed that the adherent bacteria consisted of a mixture of viable and
      nonviable PA; a PMN-associated increase in viable PA was confirmed by CFU (PA:PMN
      0.1:1, P = 0.025; PA:PMN 1:1, P = 0.005). Acute epithelial cell debris studies
      revealed a significant increase in viable PA in 96-well plates in the presence of
      epithelial freeze-thaw lysates (PA:debris 1:1, P = 0.002; PA:debris 100:1, P =
      0.002). Crystal violet staining of used lens storage cases revealed residual
      cellular debris at all time points, which was independent of microbial
      contamination; all lens cases used for periods of 9 months or more were uniformly
      associated with high levels of viable microorganisms. CONCLUSION: These results
      demonstrate that prolonged corneal inflammation with the presence of PMNs when
      confronted with simultaneous PA challenge in extended contact lens wear has the
      potential to stimulate biofilm formation on silicone hydrogel contact lenses.
      These findings further suggest that a persistent buildup of extracellular debris
      in lens storage cases may contribute to the heavy biofilms reported on these
      surfaces.

PMID- 22138710
TI  - Optical detection of vascular penetration during nerve blocks:  an in vivo human
      study.
AB  - BACKGROUND AND OBJECTIVES: Complications resulting from vascular penetration
      during nerve blocks are rare but potentially devastating events that can occur
      despite meticulous technique. In this in vivo human pilot study, we investigated
      the potential for detecting vascular penetration with optical reflectance
      spectroscopy during blocks of the sympathetic chain and the communicating ramus
      at lumbar levels. METHODS: A custom-designed needle stylet with integrated
      optical fibers was used in combination with a commercial needle shaft. The needle
      stylet was connected to a console that delivered broadband light to tissue and
      spectrally resolved light that was scattered near the stylet tip. A total of 18
      insertions were performed on 10 patients; testing for vascular penetration at the
      nerve target region was performed with aspiration and with radio-opaque contrast
      injections, visualized fluoroscopically. Optical absorption by hemoglobin was
      quantified with a blood parameter that was calculated from each spectrum. The
      blood parameter provided a measure of the difference between spectra acquired
      from the nerve target region and reference spectra acquired from blood extracted
      from a volunteer. RESULTS: In 2 insertions, vascular penetration was detected.
      Pronounced optical absorption by hemoglobin was observed to be associated with
      both of these events and absent in all other cases. The difference between the
      blood parameters obtained when vascular penetration was detected, and all other
      blood parameters were statistically significant (P = 0.006), with a diagnostic
      odds ratio of 35.4 (confidence interval, 2.21 to infinity). CONCLUSIONS: The
      results from this study suggest that optical spectroscopy has the potential to
      detect intravascular needle placement, which may in turn increase the safety of
      nerve blocks.

PMID- 22138711
TI  - The p38 mitogen-activated protein kinases modulate endothelial cell survival and
      tissue repair.
AB  - OBJECTIVE AND DESIGN: This study is designed to investigate the role of p38 MAPK
      in modulating human pulmonary artery endothelial cells (HPAECs) survival and
      tissue repair functions. METHODS: HPAECs (passage 8-12) were used for all
      experiments. Cells were treated with IL-1beta (0.5 or 2 ng/ml) or p38 inhibitor
      (SB203580 or SB220025, 5 MUM each). Cells were also transfected with 50 nM
      siRNAs. Cell length was measured using ImageJ software. Collagen gel contraction
      and wound close assay were performed to evaluate tissue repair functions.
      RESULTS: IL-1beta activated p38 MAPK and induced morphologic change of HPAECs.
      The p38 inhibitors further augmented IL-1beta-induced cell morphologic change,
      prevented cell death, and augmented collagen gel contraction. Suppression of
      p38alpha, gamma, or delta, but not p38beta resulted in cell morphologic
      alteration, and suppressing any one of p38 isoforms by siRNAs increased cell
      survival. Suppression of p38alpha or delta augmented gel contraction. While
      p38alpha suppression stimulated cell migration, suppressing the rest of three
      isoforms inhibit cell migration. Nuclear factor p65-siRNA blocked IL-1beta
      induced cell morphologic change, but did not affect p38 inhibitor-induced change.
      CONCLUSION: These findings suggest that p38 MAPK may negatively modulate tissue
      repair functions of endothelial cells via p65 independent pathway.

PMID- 22138713
TI  - Modulation of the immunogenicity of virus-like particles composed of mutant
      hepatitis B virus envelope subunits.
AB  - Virus-like particles (VLPs) are non-infectious subviral protein complexes, which
      possess structural features identical or closely related to infectious virions.
      They are utilized as delivery tools for immunologically relevant antigenic
      sequences. In order to investigate whether mutant subunits can modulate the VLP
      immunogenicity, comparative immunization studies with wild-type and non-native
      VLPs were performed. To determine whether disulfide bonding impacts on the
      immunogenicity of hepatitis B virus envelope proteins (HBsAg), mutant HBsAg
      subunits with single, double and triple cysteine residue substitutions were
      generated. The mutant proteins were expressed in cell culture, secretion
      competent non-native VLPs generated, followed by immunization studies in mice to
      measure the cellular immune response. The reduced ability of mutant HBsAg
      proteins to form disulfide bonds does not interfere with their ability to
      assemble into secretion competent VLPs. Depending on specific cysteine to alanine
      changes, VLPs could be generated with or without an increased ratio of monomeric
      versus dimeric/oligomeric subunits compared to wild-type VLPs. The utilization of
      non-native VLPs resulted in enhanced cellular immune responses and does not seem
      to depend on the ratio between monomeric or dimeric/oligomeric subunits.
      Comparative immunization studies strongly indicate that changes in the disulfide
      bonding modulate the VLP immunogenicity most likely due to structural changes. We
      hypothesize that structural features have evolved with reduced immunogenicity to
      evade the constraints imposed by the immune system. Altering VLP conformation may
      represent an attractive strategy to modulate antigen processing resulting in an
      enhanced immune response and/or a changed hierarchy of epitope presentation.

PMID- 22138712
TI  - The 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody
      inhibition: Implications for the prevalence of oseltamivir resistant variant
      viruses.
AB  - A naturally-occurring H275Y oseltamivir resistant variant of influenza A (H1N1)
      virus emerged in 2007, subsequently becoming prevalent worldwide, via an
      undetermined mechanism. To understand the antigenic properties of the H275Y
      variant, oseltamivir resistant and susceptible strains of H1N1 viruses were
      analyzed by hemagglutination inhibition (HI) and microneutralization assays. HI
      analysis with H1-positive sera obtained from seasonal flu vaccine immunized and
      non-immunized individuals, and H1-specific monoclonal antibodies, revealed that
      resistant strains exhibited a reduced reactivity to these antisera and antibodies
      in the HI assay, as compared to susceptible strains. Neutralization assay testing
      demonstrated that oseltamivir resistant H1N1 strains are also less susceptible to
      antibody inhibition during infection. Mice inoculated with a resistant clinical
      isolate exhibit 4-fold lower virus-specific antibody titers than mice infected
      with a susceptible strain under the same conditions. Resistant and sensitive
      variants of 2009 pandemic H1N1 virus did not exhibit such differences. While HA1
      and NA phylogenetic trees show that both oseltamivir resistant and susceptible
      strains belong to clade 2B, NA D354G and HA A189T substitutions were found
      exclusively, and universally, in oseltamivir resistant variants. Our results
      suggest that the reduced susceptibility to antibody inhibition and lesser in vivo
      immunogenicity of the oseltamivir resistant 2008-2009 H1N1 influenza A virus is
      conferred by coupled NA and HA mutations, and may contribute to the prevalence of
      this H1N1 variant.

PMID- 22138714
TI  - Prevalence, virology and antiviral drugs susceptibility of hepatitis B virus
      rtN238H polymerase mutation from 1865 Chinese patients with chronic hepatitis B.
AB  - Amino acid substitutions at positions rtN238T/D of the hepatitis B virus (HBV)
      polymerase have been reported as potential mutations associated with adefovir
      (ADV) resistance. In this study, we characterized the prevalence of the rtN238H
      mutation and determined the susceptibility to LAM and ADV using phenotypic
      analyzes in vitro. One thousand eight hundred and sixty-five HBsAg-positive
      patients with chronic HBV (CHB) infection were included in this study. HBV
      genotypes and reverse transcriptase (RT) mutations were determined by direct
      sequencing. Replication-competent HBV constructs containing the naturally
      occurring rtN238H mutation were generated and replication capacity and
      susceptibility to LAM and ADV in transiently transfected hepatoma cell lines were
      determined. Among 1865 enrolled HBV infected patients, 8.8% (165/1865) showed
      mutations in the rtN238 locus (143 males/22 females, 91 treatment-naive, 42 ADV
      treated, 16 LAM-treated and 16 ADV+LAM-treated), namely 86% rtN238H (142/165),
      5.5% rtN238S (9/165), 5.5% rtN238T (9/165) and 3% rtN238D (5/165). Among the
      rtN238H mutant strains, there were no significant differences between ADV- or/and
      LAM- treated patients and treated-naive patients (42% vs. 58%). Compared with
      wild-type HBV, this mutant displayed an equivalent susceptibility to LAM or ADV
      in phenotypic assays. Importantly, we found that the incidence rate of rtN238H
      was higher in HBV genotype B infected patients than HBV genotype C subsets (80.3%
      vs. 19.7%), even without exogenous selection pressures. As rtN238H did neither
      impair the viral replication efficiency nor susceptibility to LAM or ADV in
      vitro, rtN238H likely represents background polymorphisms rather than resistance
      mutations with clinical implications. The incidence of rtN238H may be associated
      with HBV genotype.

PMID- 22138715
TI  - Divergent expression patterns of IL-4 and IL-13 define unique functions in
      allergic immunity.
AB  - Interleukin 4 (IL-4) and IL-13 are critical for responses to parasitic
      helminthes. We used genetically engineered reporter mice to assess the temporal
      and spatial production of these cytokines in vivo. In lymph nodes, IL-4, but not
      IL-13, was made by follicular helper T cells (T(FH) cells). In contrast, tissue
      type 2 helper T cells (T(H)2 cells) produced both cytokines. There was also
      divergent production of IL-4 and IL-13 among cells of the innate immune system,
      whereby basophils produced IL-4, whereas innate helper type 2 cells (Ih2 cells)
      produced IL-13. IL-13 production by T(H)2 and Ih2 cells was dependent on the
      transcription factor GATA-3, which was present in large amounts in these cells,
      and in contrast to the small amount of GATA-3 in T(FH) cells and basophils. The
      distinct localization and cellular expression of IL-4 and IL-13 explains their
      unique roles during allergic immunity.

PMID- 22138716
TI  - Transendothelial migration of lymphocytes mediated by intraendothelial vesicle
      stores rather than by extracellular chemokine depots.
AB  - Chemokines presented by the endothelium are critical for integrin-dependent
      adhesion and transendothelial migration of naive and memory lymphocytes. Here we
      found that effector lymphocytes of the type 1 helper T cell (T(H)1 cell) and type
      1 cytotoxic T cell (T(C)1 cell) subtypes expressed adhesive integrins that
      bypassed chemokine signals and established firm arrests on variably inflamed
      endothelial barriers. Nevertheless, the transendothelial migration of these
      lymphocytes strictly depended on signals from guanine nucleotide-binding proteins
      of the G(i) type and was promoted by multiple endothelium-derived inflammatory
      chemokines, even without outer endothelial surface exposure. Instead,
      transendothelial migration-promoting endothelial chemokines were stored in
      vesicles docked on actin fibers beneath the plasma membranes and were locally
      released within tight lymphocyte-endothelial synapses. Thus, effector T
      lymphocytes can cross inflamed barriers through contact-guided consumption of
      intraendothelial chemokines without surface-deposited chemokines or
      extraendothelial chemokine gradients.

PMID- 22138719
TI  - Morphology-directed synthesis of Co3O4 nanotubes based on modified Kirkendall
      effect and its application in CH4 combustion.
AB  - We reported the morphology-directed synthesis of Co(3)O(4) nanotubes via
      interfacial reaction of NaOH with pre-fabricated CoC(2)O(4).2H(2)O nanorods based
      on modified Kirkendall effect. The as-obtained Co(3)O(4) nanotubes showed
      excellent activity and durability in catalytic combustion of CH(4).

PMID- 22138717
TI  - NANOSTRUCTURED PROBES FOR IN VIVO GENE DETECTION.
AB  - The ability to visualize in real-time the expression dynamics and localization of
      specific RNAs in vivo offers tremendous opportunities for biological and disease
      studies including cancer detection. However, quantitative methods such as real
      time PCR and DNA microarrays rely on the use of cell lysates thus not able to
      obtain important spatial and temporal information. Fluorescence proteins and
      other reporter systems cannot image endogenous RNA in living cells. Fluorescence
      in situ hybridization (FISH) assays require washing to achieve specificity,
      therefore can only be used with fixed cells. Here we review the recent
      development of nanostructured probes for living cell RNA detection, and discuss
      the biological and engineering issues and challenges of quantifying gene
      expression in vivo. In particular, we describe methods that use oligonucleotide
      probes, combined with novel delivery strategies, to image the relative level,
      localization and dynamics of RNA in live cells. Examples of detecting endogenous
      mRNAs, as well as imaging their subcellular localization are given to illustrate
      the biological applications, and issues in probe design, delivery and target
      accessibility are discussed. The nanostructured probes promise to open new and
      exciting opportunities in sensitive gene detection for a wide range of biological
      and medical applications.

PMID- 22138720
TI  - Screening of soy and milk protein hydrolysates for their ability to activate the
      CCK1 receptor.
AB  - The cholecystokinin receptor-type 1 (CCK1R) is a G-protein coupled receptor
      localized in the animal gastrointestinal tract. Receptor activation by the
      natural peptide ligand CCK leads to a feeling of satiety. In this study,
      hydrolysates from soy and milk proteins were evaluated for their potential to
      activate the CCK1R, assuming that bioactive peptides with a satiogenic effect can
      be used as an effective therapeutic strategy for obesity. Different protein
      hydrolysates were screened with a cell-based bioassay, which relies on the
      generation of a fluorescent signal upon receptor activation. Fluorescence was
      monitored using a fluorescence plate reader and confocal microscopy. Results from
      the fluorescence plate reader were biased by background autofluorescence of the
      protein hydrolysate matrices, which makes the fluorescence plate reader
      inappropriate for the evaluation of complex formulations. Measurements with the
      confocal microscope resulted in reliable and specific results. The latter
      approach showed that the gastrointestinal digested 7S fraction of soy protein
      demonstrates CCK1R activity.

PMID- 22138718
TI  - Are commonly used psychoactive medications associated with lower urinary tract
      symptoms?
AB  - PURPOSE: Lower urinary tract symptoms (LUTS) such as urinary frequency and
      urgency are bothersome and associated with reduced quality of life. Atypical
      antipsychotics (AAPs) have been implicated in increasing the risk of urinary
      incontinence. In a large community-based sample of men and women, we examined the
      associations of AAP and selective serotonin reuptake inhibitor (SSRIs) use with
      LUTS. METHODS: Data were collected (2002-2005) from a generalizable sample of
      Boston, MA, USA, residents aged 30-79 (N = 5503). LUTS were assessed using the
      American Urologic Association Symptom Index (AUA-SI). The prevalence of
      clinically-significant LUTS was estimated using a cutoff AUA-SI score of 8+ to
      indicate moderate-to-severe symptoms. Confounder-adjusted odds ratios (ORs) and
      95% confidence intervals (CI) were calculated from multivariate logistic
      regression to estimate the associations for psychoactive drugs used in the
      previous month (SSRIs, AAPs, both) and LUTS. RESULTS: Among women, AAP users had
      a higher prevalence of LUTS (46.2%) compared with SSRI users (23.5%) and those
      with depressive symptoms not using SSRIs or AAPs (26.3%). Corresponding
      prevalence estimates among men were 32.7%, 29.8%, and 33.3%. In multivariate
      models, AAP use was significantly associated with LUTS among women when used
      either with (OR = 2.72, 95% CI:1.45-5.10) or without (OR = 3.05, 95% CI:1.30
      7.16) SSRIs, but SSRI use without AAP use was not associated with LUTS compared
      with nonusers without depressive symptoms. No associations were observed among
      men. CONCLUSIONS: In our study, AAPs but not SSRIs were associated with increased
      prevalence of LUTS among women only. Further prospective research is needed to
      determine time sequence and cause and effect.

PMID- 22138721
TI  - Regulation of gene expression and biochemical changes in small intestine of
      newborn diabetic rats by exogenous ghrelin.
AB  - The aim of this study was to investigate (i) the cholecystokinin, somatostatin
      and apelin mRNA levels, (ii) the changes in levels and localization of these
      peptides, (iii) relation between these peptides, (iv) antiapoptotic effects and
      (v) antioxidant effects of ghrelin. The rats were divided into four groups second
      day after birth. These groups were respectively treated with physiological
      saline, ghrelin (100MUg/kg/day), streptozotocin (100mg/kg), ghrelin and
      streptozotocin. After four weeks, small intestine and blood samples were taken
      from rats. Cholecystokinin mRNA and peptide, somatostatin mRNA, release to
      duodenal lumen of apelin peptide and apelin mRNA signals decreased in ghrelin
      treated diabetic rats compared to the diabetic group. There was no statistically
      significant difference among the four groups for somatostatin and apelin
      peptides. Caspase-3 signals were not observed only in diabetic group treated with
      ghrelin. Caspase-8 signals were increased while PCNA signals were decreased in
      diabetic group given ghrelin compared to diabetic group. Small intestine CAT,
      SOD, GP(x) and GST activities and GSH levels were decreased and LPO, PC levels
      were increased in diabetic rats. Administration of ghrelin to diabetic rats
      caused an increase in intestinal CAT, SOD, GP(x) and GST activities and GSH
      levels, while PC levels decreased. As a result, we observed positive changes in
      diabetic rats treated with ghrelin in both microscopic and biochemical studies.
      We can suggest that ghrelin may be an important hormone for the treatment of
      diabetes.

PMID- 22138723
TI  - Persons, post-persons and thresholds.
AB  - DeGrazia argues that post-persons have as much justification in believing that
      they have higher moral status than persons as persons have in believing that they
      have higher moral status than animals. DeGrazia's claim presupposes that what
      Buchanan calls the "moral equality assumption" is false. This article argues that
      DeGrazia has given us no reason to disbelieve the moral equality assumption.
      Further, even if DeGrazia's arguments about moral status were sound, it is
      unclear that his first-order normative claims about how we should weigh human
      against animal interests would follow.

PMID- 22138722
TI  - Clinical trial of allogeneic cultured dermal substitutes for intractable skin
      ulcers.
AB  - The effect of allogeneic cultured dermal substitute (CDS) on wound healing was
      evaluated in 9 intractable skin ulcers in 5 patients who had failed to improve
      despite conventional topical treatment with basic fibroblast growth factor (bFGF)
      for more than 2 months. In general, the topical application of bFGF is effective
      in facilitating wound healing. However, skin regeneration was very slow in the
      present 9 cases. In this study, to improve the condition of these wounds,
      allogeneic CDS was applied once a week for 2 months. The wound healing process
      was evaluated, focusing on the reduction ratio of wound size through the
      granulation tissue formation associated with epithelialization. In all 9 cases,
      the wound size was successfully decreased after the application of CDS, and
      ulcers were completely resurfaced in 2 cases. In all cases, except the 2 cases
      showing complete wound closure, the mean wound size decreased to 33.3% of the
      original size, i.e., a mean reduction ratio of 33.3%. The present results
      indicate that allogeneic CDS can promote wound healing of intractable skin ulcers
      that fail to improve despite treatment with bFGF.

PMID- 22138724
TI  - How to avoid unfair discrimination against disabled patients in healthcare
      resource allocation.
AB  - The paper proposes a new method of researching public opinion for the purposes of
      valuing the outcomes of healthcare interventions. The issue I address is that,
      under the quality-adjusted life-year system, disabled patients face a higher cost
      effectiveness hurdle than able-bodied patients. This seems inequitable. The
      author considers the alternative approaches to valuing healthcare interventions
      that have been proposed, and shows that all of them face the same problem. It is
      proposed that to value an outcome, instead of researching the general public, the
      population that is to be targeted with the intervention should be researched.

PMID- 22138725
TI  - Terminal sedation: an emotional decision in end-of-life care.
AB  - A patient with end-stage motor neurone disease was admitted for hospice care with
      worsening bulbar symptoms. Although he initially walked onto the ward he became
      very distressed and asked for sedation. After much discussion, this man was
      deeply sedated, and after some harrowing days, died. Was it right to provide
      terminal sedation? What should the threshold be for such treatment? How should
      our personal reservations affect how we approach the distressed patient in an end
      of-life situation?

PMID- 22138726
TI  - Just implementation of human papillomavirus vaccination.
AB  - Many countries are now implementing human papillomavirus vaccination. There is
      disagreement about who should receive the vaccine. Some propose vaccinating both
      boys and girls in order to achieve the largest possible public health impact.
      Others regard this approach as too costly and claim that only girls should be
      vaccinated. We question the assumption that decisions about human papillomavirus
      vaccination policy should rely solely on estimates of overall benefits and costs.
      There are important social justice aspects that also need to be considered.
      Policy makers should consider how to best protect individuals who will remain
      unvaccinated through no fault of their own. This is especially important if these
      individuals are already disadvantaged in other ways and if vaccinating other
      people increases their risk of infection.

PMID- 22138727
TI  - Retractions in the medical literature: how can patients be protected from risk?
AB  - BACKGROUND: Medical research so flawed as to be retracted may put patients at
      risk by influencing treatments. OBJECTIVE: To explore hypotheses that more
      patients are put at risk if a retracted paper appears in a journal with a high
      impact factor (IF) so that the paper is widely read; is written by a 'repeat
      offender' author who has produced other retracted research; or is a clinical
      trial. METHODS: English language papers (n=788) retracted from the PubMed
      database between 2000 and 2010 were evaluated. Only those papers retracting
      research with humans or freshly derived human material were included; 180
      retracted primary papers (22.8%) met inclusion criteria. Subjects enrolled and
      patients treated were tallied, both in the retracted primary studies and in 851
      secondary studies that cited a retracted primary paper. RESULTS: Retracted papers
      published in high-IF journals were cited more often (p=0.0004) than those in low
      IF journals, but there was no difference between high- and low-IF papers in
      subjects enrolled or patients treated. Retracted papers published by 'repeat
      offender' authors did not enrol more subjects or treat more patients than papers
      by one-time offenders, nor was there a difference in number of citations.
      However, retracted clinical trials treated more patients (p=0.0002) and inspired
      secondary studies that put more patients at risk (p=0.0019) than did other kinds
      of medical research. CONCLUSIONS: If the goal is to minimise risk to patients,
      the appropriate focus is on clinical trials. Clinical trials form the foundation
      of evidence-based medicine; hence, the integrity of clinical trials must be
      protected.

PMID- 22138728
TI  - Threats and offers in community mental healthcare.
AB  - Making threats and offers to patients is a strategy used in community mental
      healthcare to increase treatment adherence. In this paper, an ethical analysis of
      these types of proposal is presented. It is argued (1) that the primary ethical
      consideration is to identify the professional duties of care held by those
      working in community mental health because the nature of these duties will enable
      a threat to be differentiated from an offer, (2) that threatening to act in a way
      that would equate with a failure to uphold the requirements of these duties is
      wrong, irrespective of the benefit accrued through treatment adherence and (3)
      that making offers to patients raises a number of secondary ethical
      considerations that need to be judged on their own merit in the context of
      individual patient care. The paper concludes by considering the implications of
      these arguments, setting out a pathway designed to assist community mental
      healthcare practitioners to determine whether making a specific proposal to a
      patient is right or wrong.

PMID- 22138729
TI  - Still unconvinced, but still tentative: a reply to DeGrazia.
AB  - David DeGrazia's article provides a careful and fair rendition of my position on
      the possibility of post-persons. However, I am unconvinced that he has shown that
      such beings are possible. My view is based on two assumptions: (1) the concept of
      moral status is a threshold concept; and (2) the most plausible understanding of
      moral status as a threshold concept is a Kantian respect-based view, according to
      which all and only those beings who have the capacity to be accountable for
      reasons have the high status we associate with persons. I argue that the superior
      beings DeGrazia describes would be more morally admirable than us, but would not
      have a higher moral status. I also argue that, contrary to DeGrazia, even the
      most intelligent of canines do not have the capacity for accountability for
      reasons, even in an attenuated form. I then argue that DeGrazia faces a painful
      dilemma: either he must give up the assumption that moral status (so far as
      persons are concerned) is a threshold concept and say that for any two beings
      with the capacity for accountability for reasons, the one with the greater
      capacity has a higher moral status; or he must retain the view that moral status
      is a threshold concept but concede that he has not account of where the threshold
      lies.

PMID- 22138730
TI  - [Well-being of patients receiving specialized palliative care at home or in
      hospital].
AB  - BACKGROUND: A major goal of palliative care is sustaining quality of life (QoL)
      for patients suffering from severe symptoms, which is determined by physical and
      psychological consequences of an illness as well as other factors, such as the
      meaning of life and family support. Patients have reported high levels of QoL
      despite worsening symptoms. The self-estimated QoL of patients receiving
      outpatient and inpatient palliative care was analyzed using retrospective data
      from the German Hospice and Palliative Care Evaluation (HOPE). MATERIALS AND
      METHODS: A descriptive analysis of questionnaires given to 2,030 patients (1,616
      inpatients, 414 outpatients) and their professional care takers was carried out
      assessing symptoms, well-being and care-related information. RESULTS: At the
      beginning of treatment inpatients had a higher symptom burden than outpatients.
      Reduced pain, tiredness and weakness and improved well-being allowed inpatients
      to be discharged. Outpatients suffering from severe dyspnea, constipation and
      anxiety were more likely to be admitted to hospital. Well-being was associated
      with symptom burden, weakness and tiredness in both self-evaluation and care
      taker assessment particularly for outpatients. CONCLUSIONS: While tiredness and
      weakness influenced QoL especially for outpatients, patient-specific factors may
      surpass them in patient perception. To improve the QoL of palliative care
      patients, individual factors must be assessed in addition to symptom control.

PMID- 22138731
TI  - Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule
      in vitro.
AB  - BACKGROUND: To determine whether the cytoskeletal drugs H-7 and Latrunculin B
      (LAT-B) inhibit posterior capsular opacification (PCO) in the cultured human lens
      capsular bag. METHODS: Following extracapsular cataract (lens) extraction in
      human donor eyes, the capsular bag was prepared and cultured by standard
      techniques. Forty-eight capsular bags were studied, of which 13 were treated with
      H-7 (50, 100 or 300 MUM), 12 with 1% BSS (vehicle of H-7), 11 with LAT-B (2, 5 or
      10 MUM), and 12 with 0.25% DMSO (vehicle of LAT-B). Forty out of the 48 capsular
      bags were from paired eyes of 20 donors, with one bag being treated with H-7/LAT
      B and the other with BSS/DMSO for each pair, including 20 for the H-7-BSS
      protocol and 20 for the LAT-B-DMSO protocol. The medium with the cytoskeletal
      drug/vehicle was replaced every 3-4 days for 4 weeks. PCO was assessed daily
      using inverted phase-contrast microscopy, and scored on a 4-point scale. RESULTS:
      In all cultures with BSS or DMSO, residual lens epithelial cells (LECs) on the
      anterior capsule migrated to and proliferated on the posterior capsule by 3-7
      days, and apparent LEC growth on the posterior capsule with severe capsular
      wrinkling (PCO Grade 3) was seen by 2-3 weeks. When treated continuously with H-7
      or LAT-B, the migration and proliferation of LECs and the capsular wrinkling were
      inhibited in a dose-dependent manner, with the inhibition being complete (PCO
      Grade 0) in the 300 MUM H-7 (n = 8, p < 0.001) or 10 MUM LAT-B culture (n = 3, p
      = 0.002). CONCLUSION: H-7 and LAT-B dose-dependently inhibited PCO formation in
      the cultured human lens capsular bags, suggesting that cytoskeletal drugs might
      prevent PCO formation after surgery in the human eye.

PMID- 22138732
TI  - The effect of connexin43 on the level of vascular endothelial growth factor in
      human retinal pigment epithelial cells.
AB  - BACKGROUND: Connexins (Cx) are the basic units of gap junctions and contribute to
      cellular integrity by promoting intercellular communication. Disruption of the
      retinal pigment epithelial monolayer may be an early event in the pathogenesis of
      age-related macular degeneration, a condition in which vascular endothelial
      growth factor (VEGF) is known to be of importance. This study was designed to
      assess the effect of connexin43 (Cx43) expression and gap junctional
      intercellular communication (GJIC) on the expression and secretion of VEGF from
      the retinal pigment epithelium under normal cell culture and oxidative stress
      conditions. METHODS: Stable cell lines of ARPE-19 were produced in which wild
      type Cx43 was either over-expressed, down-regulated by targeted shRNA, or
      functionally inhibited by co-expression of a disease-linked dominant-negative
      mutant (G21R). Pharmacologic blockade of GJIC was accomplished with flufenamic
      acid. Oxidant challenge was performed with tert-butyl hydroperoxide (tBH). VEGF
      gene expression and secretion were assessed by real-time PCR and ELISA
      respectively. RESULTS: Over-expression of Cx43 in ARPE-19 cells reduced both gene
      expression and secretion of VEGF. Down-regulation of Cx43 increased gene
      expression and secretion of VEGF. Increased secretion of VEGF was also observed
      in ARPE-19 cells expressing a dominant-negative mutant of Cx43, and when GJIC was
      blocked. Over-expression of Cx43 reduced tBH-induced secretion of VEGF from ARPE
      19 cells. CONCLUSIONS: These studies show that Cx43 protects against oxidative
      stress-induced VEGF secretion in ARPE-19 cells, and thus has important
      implications in understanding the pathogenesis of age-related macular
      degeneration.

PMID- 22138733
TI  - Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis:
      implications for the investigation of the natural history of incidental
      steatosis.
AB  - OBJECTIVES: To determine a highly specific liver attenuation threshold at
      unenhanced CT for biopsy-proven moderate to severe hepatic steatosis (>=30% at
      histology). METHODS: 315 asymptomatic adults (mean age +/- SD, 31.5 +/- 10.1
      years; 207 men, 108 women) underwent same-day unenhanced liver CT and ultrasound
      guided liver biopsy. Blinded to biopsy results, CT liver attenuation was measured
      using standard region-of-interest methodology. Multiple linear regression
      analysis was used to assess the relationship of CT liver attenuation with patient
      age, gender, BMI, CT system, and hepatic fat and iron content. RESULTS: Thirty
      nine subjects had moderate to severe steatosis and 276 had mild or no steatosis.
      A liver attenuation threshold of 48 HU was 100% specific (276/276) for moderate
      to severe steatosis, with no false-positives. Sensitivity, PPV and NPV at this HU
      threshold was 53.8%, 100% and 93.9%. Hepatic fat content was the overwhelming
      determinant of liver attenuation values, but CT system (P < 0.001), and hepatic
      iron (P = 0.035) also had a statistically significant independent association.
      CONCLUSIONS: Unenhanced CT liver attenuation alone is highly specific for
      moderate to severe hepatic steatosis, allowing for confident non-invasive
      identification of large retrospective/prospective cohorts for natural history
      evaluation of incidental non-alcoholic fatty liver disease. Low sensitivity,
      however, precludes effective population screening at this threshold. KEY POINTS:
      * Unenhanced CT liver attenuation is highly specific for diagnosing
      moderate/severe hepatic steatosis. * Unenhanced CT can identify large cohorts for
      epidemiological studies of incidental steatosis. * Unenhanced CT is not, however,
      effective for population screening for hepatic steatosis.

PMID- 22138734
TI  - In vivo characterisation of soft tissue tumours by 1.5-T proton MR spectroscopy.
AB  - OBJECTIVES: To determine whether proton magnetic resonance spectroscopy (1H-MRS)
      can help differentiate between benign and malignant soft tissue lesions, and to
      assess if there is a correlation between 1H-MRS data and the mitotic index.
      METHODS: MR measurements were performed in 43 patients with soft tissue tumours
      >15 mm in diameter. Six cases were excluded for technical failure. Examinations
      were performed at 1.5 T using a single-voxel point resolved spectroscopy sequence
      (PRESS) with TR/TE = 2000/150 ms. The volume of interest was positioned within
      the lesion avoiding inclusion of necrotic regions. In all patients, a
      histological diagnosis was obtained and the corresponding mitotic index was also
      computed. 1H-MRS results and histopathological findings were compared using the
      chi-squared test and correlation coefficient. RESULTS: Choline was detected in
      18/19 patients with malignant tumours and in 3/18 patients with benign lesions.
      The three benign lesions included one desmoid tumour, one ossificans myositis and
      one eccrine spiradenoma. Choline was not detected in 15 patients with benign
      lesions or in one patient with dermatofibrosarcoma protuberans. Resulting 1H-MRS
      sensitivity and specificity were 95% and 83% respectively. CONCLUSIONS: Absence
      of choline peak is highly predictive of benign tumours suggesting that 1H-MRS can
      help to differentiate malignant from benign tumours. KEY POINTS: * 1H-MRS may
      allow differentiation between benign and malignant soft tissue lesions * Absence
      of choline peak is highly predictive of benign soft tissue lesions * Malignant
      tumours with a mitotic index >2/10 HPF had a positive choline peak * A choline
      peak may still be identified in some benign tumours.

PMID- 22138736
TI  - The impact of chief executive officer optimism on hospital strategic decision
      making.
AB  - BACKGROUND: Previous strategic decision making research has focused mostly on the
      analytical positioning approach, which broadly emphasizes an alignment between
      rationality and the external environment. In this study, we propose that hospital
      chief executive optimism (or the general tendency to expect positive future
      outcomes) will moderate the relationship between comprehensively rational
      decision-making process and organizational performance. PURPOSE: The purpose of
      this study was to explore the impact that dispositional optimism has on the well
      established relationship between rational decision-making processes and
      organizational performance. Specifically, we hypothesized that optimism will
      moderate the relationship between the level of rationality and the organization's
      performance. We further suggest that this relationship will be more negative for
      those with high, as opposed to low, optimism. METHODS: We surveyed 168 hospital
      CEOs and used moderated hierarchical regression methods to statically test our
      hypothesis. FINDINGS: On the basis of a survey study of 168 hospital CEOs, we
      found evidence of a complex interplay of optimism in the rationality
      organizational performance relationship. More specifically, we found that the two
      way interactions between optimism and rational decision making were negatively
      associated with performance and that where optimism was the highest, the
      rationality-performance relationship was the most negative. Executive optimism
      was positively associated with organizational performance. We also found that
      greater perceived environmental turbulence, when interacting with optimism, did
      not have a significant interaction effect on the rationality-performance
      relationship. PRACTICE IMPLICATIONS: These findings suggest potential for broader
      participation in strategic processes and the use of organizational development
      techniques that assess executive disposition and traits for recruitment
      processes, because CEO optimism influences hospital-level processes. Research
      implications include incorporating greater use of behavior and cognition
      constructs to better depict decision-making processes in complex organizations
      like hospitals.

PMID- 22138735
TI  - Iterative decomposition of water and fat with echo asymmetry and least-squares
      estimation (IDEAL) imaging of multiple myeloma: initial clinical efficiency
      results.
AB  - OBJECTIVES: To evaluate the effectiveness of the iterative decomposition of water
      and fat with echo asymmetric and least-squares estimation (IDEAL) MRI to quantify
      tumour infiltration into the lumbar vertebrae in myeloma patients without visible
      focal lesions. METHODS: The lumbar spine was examined with 3 T MRI in 24 patients
      with multiple myeloma and in 26 controls. The fat-signal fraction was calculated
      as the mean value from three vertebral bodies. A post hoc test was used to
      compare the fat-signal fraction in controls and patients with monoclonal
      gammopathy of undetermined significance (MGUS), asymptomatic myeloma or
      symptomatic myeloma. Differences were considered significant at P < 0.05. The fat
      signal fraction and beta(2)-microglobulin-to-albumin ratio were entered into the
      discriminant analysis. RESULTS: Fat-signal fractions were significantly lower in
      patients with symptomatic myelomas (43.9 +/-19.7%, P < 0.01) than in the other
      three groups. Discriminant analysis showed that 22 of the 24 patients (92%) were
      correctly classified into symptomatic or non-symptomatic myeloma groups.
      CONCLUSIONS: Fat quantification using the IDEAL sequence in MRI was significantly
      different when comparing patients with symptomatic myeloma and those with
      asymptomatic myeloma. The fat-signal fraction and beta(2)-microglobulin-to
      albumin ratio facilitated discrimination of symptomatic myeloma from non
      symptomatic myeloma in patients without focal bone lesions. KEY POINTS: * A new
      magnetic resonance technique (IDEAL) offers new insights in multiple myeloma. *
      Fat-signal fractions were lower in patients with symptomatic myelomas than in
      those with asymptomatic myelomas. * The beta2-microglobulin-to-albumin ratio also
      aided discrimination of symptomatic myeloma. * The fat-signal fraction may
      provide information about the myeloma cell mass.

PMID- 22138737
TI  - Relational coordination promotes quality of chronic care delivery in Dutch
      disease-management programs.
AB  - BACKGROUND: Previous studies have shown that relational coordination is
      positively associated with the delivery of hospital care, acute care, emergency
      care, trauma care, and nursing home care. The effect of relational coordination
      in primary care settings, such as disease-management programs, remains unknown.
      PURPOSE: This study examined relational coordination between general
      practitioners and other professionals in disease-management programs and assessed
      the impact of relational coordination on the delivery of chronic illness care.
      METHODOLOGY: Professionals (n = 188; response rate = 57%) in 19 disease
      management programs located throughout the Netherlands completed surveys that
      assessed relational coordination and chronic care delivery. We used a cross
      sectional study design. FINDINGS: Our study demonstrated that the delivery of
      chronic illness care was positively related to relational coordination. We found
      positive relationships with community linkages (r = .210, p < .01), self
      management support (r = .217, p < .01), decision support (r = .190, p < .01),
      delivery system design (r = .278, p < .001), and clinical information systems (r
      = .193, p < .01). Organization of the health delivery system was not
      significantly related to relational coordination. The regression analyses showed
      that even after controlling for all background variables, relational coordination
      still significantly affected chronic care delivery (beta = .212, p <= .01). As
      expected, our findings showed a lower degree of relational coordination among
      general practitioners than between general practitioners and other core disease
      management team members: practice nurses (M = 2.69 vs. 3.73; p < .001),
      dieticians (M = 2.69 vs. 3.07; p < .01), physical therapists (M = 2.69 vs. 3.06;
      p < .01), medical specialists (M = 2.69 vs. 3.16; p < .01), and nurse
      practitioners (M = 2.69 vs. 3.19; p < .001). PRACTICE IMPLICATIONS: The
      enhancement of relational coordination among core disease-management
      professionals with different disciplines is expected to improve chronic illness
      care delivery.

PMID- 22138738
TI  - Implementing person-centered care in nursing homes.
AB  - BACKGROUND: Charged with caring for frail and disabled elders, nursing homes are
      complex organizations that operate under high regulatory scrutiny and low public
      opinion. Despite efforts to improve, many nursing home residents receive poor
      care. By focusing on residents' relationships, life experiences, abilities, and
      preferences, person-centered care represents an innovation in nursing home care.
      Because person-centered care requires organization-wide change, implementation
      can be challenging. PURPOSE: The purpose of this research is to apply innovation
      implementation theory to understand factors and conditions that help or hinder
      the implementation of person-centered care in nursing homes. METHODOLOGY: Data
      come from the Person-Centered Care Program conducted by the Carolinas Center for
      Medical Excellence. Eight nursing homes participated in the Person-Centered Care
      Program for 1 year. A multiple-case-study design and pattern-matching logic were
      employed to examine organizational factors associated with implementation
      effectiveness. Data sources included semistructured key informant interviews,
      archival documents, surveys, and expert rankings of nursing homes' implementation
      effectiveness. FINDINGS: On the basis of this research, we suggest that effective
      implementation of organization-wide change in nursing homes is associated with
      high-quality management communications about the change, organizational readiness
      for change, and favorable perceptions from direct care providers about the
      priority of the innovation to the organization. Notably, neither the amount of
      training nor the financial resources dedicated to person-centered care were
      associated with implementation effectiveness. PRACTICE IMPLICATIONS: Effective
      implementation of person-centered care in nursing homes is most likely when
      management follows through with plans as advertised, when leadership teams have
      confidence in their ability to meet goals for change, and when change fosters
      smooth operations in the daily routines of direct care providers.

PMID- 22138739
TI  - The impact of bullying on health care administration staff: reduced commitment
      beyond the influences of negative affectivity.
AB  - BACKGROUND: Investigations of workplace bullying in health care settings have
      tended to focus on nurses or other clinical staff. However, the organizational
      and power structures enabling bullying in health care are present for all
      employees, including administrative staff. PURPOSES: : The purpose of this study
      was to specifically focus on health care administration staff and examine the
      prevalence and consequences of workplace bullying in this occupational group.
      METHODOLOGY/APPROACH: A cross-sectional study was conducted based on
      questionnaire data from health care administration staff who work across
      facilities within a medium to large health care organization in Australia. The
      questionnaire included measures of bullying, negative affectivity (NA), job
      satisfaction, organizational commitment, well-being, and psychological distress.
      The three hypotheses of the study were that (a) workplace bullying will be linked
      to negative employee outcomes, (b) individual differences on demographic factors
      will have an impact on these outcomes, and (c) individual differences in NA will
      be a significant covariate in the analyses. The hypotheses were tested using t
      tests and analyses of covariances. FINDINGS: A total of 150 health care
      administration staff completed the questionnaire (76% response rate). Significant
      main effects were found for workplace bullying, with lower organizational
      commitment and well-being with the effect on commitment remaining over and above
      NA. Main effects were found for age on job satisfaction and for employment type
      on psychological distress. A significant interaction between bullying and
      employment type for psychological distress was also observed. Negative
      affectivity was a significant covariate for all analyses of covariance. PRACTICE
      IMPLICATIONS: The applications of these results include the need to consider the
      occupations receiving attention in health care to include administration
      employees, that bullying is present across health care occupations, and that some
      employees, particularly part-time staff, may need to be managed slightly
      differently to the full-time workforce.

PMID- 22138740
TI  - [Tibial nerve paresis in eight dairy cows: symptomatic therapy with a synthetic
      resin cast].
AB  - OBJECTIVE: Tibial paresis is commonly seen in bovine practice as a sequel to
      dystocia. The tibial nerve supplies the extensor muscles of the hock joint and
      the flexor muscles of the digits; affected cows are lame and have a dropped hock
      and knuckling of the fetlock. Complete functional recovery occurs not
      consistently after a conservative "wait and see" approach. The aim of this study
      was to investigate the usefulness of a cast applied to the lower portion of the
      affected limb as a supportive treatment of tibial nerve paresis in cows.
      MATERIALS AND METHODS: Eight dairy cows with tibial nerve paresis from different
      farms were presented for treatment. Seven cows had unilateral tibial nerve
      paresis and one cow, which was barely able to stand, had bilateral tibial
      paresis. The affected legs of the seven cows with unilateral paresis and the more
      severely affected leg of the remaining cow were stabilized using a cast made of
      synthetic resin. The claws and the skin of the affected limbs were cleaned and a
      thick layer of cotton was applied to pad the leg from the foot to the hock. A
      cast was then applied with the foot and metatarsus aligned in a straight line.
      The cast included the entire foot and extended to the hock. The cast was removed
      after 4 weeks. RESULTS: All of the eight cows could be kept in their normal
      environment. They were able to walk well with the cast and were only mildly lame.
      Feed intake and milk yield increased. After removal of the cast, seven of the
      eight cows walked normally, including the cow of which both legs had been
      affected. One cow was slightly lame with a dropped hock after cast removal but
      showed a normal gait 3 weeks later. CONCLUSIONS AND CLINICAL RELEVANCE: In cows
      with tibial paresis, casting of the lower portion of the leg was a useful
      supportive treatment that resulted in restoration of normal gait. In seven of
      eight treated cows limb function was normal after 4 weeks, and in one cow after 7
      weeks. This supportive therapeutic procedure is straightforward, minimizes
      aftercare and allows the cow to be kept in her normal environment.

PMID- 22138741
TI  - [Treatment of long bone fractures in 125 newborn calves. A retrospective study].
AB  - OBJECTIVES: Retrospective study of the causes, location, configuration, treatment
      and outcome of long bone fractures in newborn calves. MATERIAL AND METHODS: The
      medical records of 125 calves presented during a 16-year period because of
      fracture of the humerus (3 calves), radius/ulna (14), femur (50) or tibia (58)
      were evaluated. The majority of calves (61.6%) sustained the fractures during
      assisted delivery. Of 125 calves, 107 were treated and 18 were euthanized because
      of concurrent diseases. Conservative treatment was used in 16 calves and surgical
      treatment in 91. Four of the latter were euthanized because of muscle contraction
      which prevented fracture reduction, and five others died in surgery. RESULTS:
      Fracture healing occurred after conservative treatment in 10 of 16 calves and
      after surgical treatment in 44 of 82 calves. The outcome was better in calves
      with plate and clamp-rod internal fixation (37/58 healed) than with
      intramedullary pinning (4/16 healed) or external fixation (3/8 healed). There
      were significant associations (chi2-test, p<0.01) between concurrent diseases and
      choice of therapy and fracture healing. Of 67 calves that developed
      complications, only 26 could be cured. Common complications were implant
      loosening and instability, which were often followed by osteomyelitis and sepsis.
      Implants were removed in 39 of 44 surgically treated calves that survived up to 6
      months postoperatively. Long-term follow up (> 6 months postoperatively) by
      clinical and radiographic re-examination (25 calves) or telephone inquiry (29
      calves) revealed that 54 animals were sound and had returned to their intended
      use. CONCLUSIONS AND CLINICAL RELEVANCE: The treatment of long bone fractures in
      newborn calves remains difficult because of a high incidence of complications.
      These are most likely attributable to trauma during delivery, which results in
      insufficient colostrum intake and predisposes to concurrent diseases. In
      addition, the characteristics of juvenile bones do not provide sufficient
      physical strength for implants. Therefore, professional and diligent assistance
      during forced extraction, particularly in presentations with "stifle lock" or
      "hip lock", is required to minimize the incidence of long bone fractures in
      newborn calves. Most cases require surgical fixation, which is time consuming,
      expensive and carries a guarded prognosis.

PMID- 22138742
TI  - [Inappropriate lactation syndrome in goats--case collection and experiences with
      mastectomy].
AB  - OBJECTIVE: Hobby keeping of goats and sheep confronts veterinarians with new
      challenges that rarely have to be faced in livestock husbandry. During the last
      five years five goats were presented to the Clinic for Animal Reproduction,
      Faculty of Veterinary Medicine, Freie Universitat Berlin, Germany, with
      inappropriate lactation syndrome. Four of these animals had been previously
      treated with cabergoline without enduring success. According to the request of
      the owners (informed consent) and the clinical severity of the cases, a
      mastectomy was performed in all five animals. MATERIAL AND METHODS: Surgery was
      performed under general anaesthesia using ketamine and xylazine, and with the
      patients in a recumbent position. RESULTS: Mastectomy in small ruminants requires
      knowledge of the anatomy of the udder and the possible positions of the supplying
      blood vessels. Our patients displayed a variety of dispositions of the Vena
      epigastrica caudalis superficialis. Special attention should be paid to a careful
      and blunt dissection of the mammary gland, and immediate control of haemorrhage,
      to maintain a clear view on the anatomic structures. Furthermore, dissection of
      the glandular tissue should be strictly avoided to prevent milk contamination of
      the surgical area. A sufficient skin flap has to be left to cover the surgical
      area after removal of the udder. CONCLUSION AND CLINICAL RELEVANCE: Even though
      udder amputation appears to be a radical and high-risk procedure, all five goats
      survived the surgery. The wound healing occurred in a reasonable time without any
      severe complications. In goats that are kept as "hobby animals" and in which an
      inappropriate lactation syndrome cannot be treated conservatively, mastectomy is
      a reasonable and promising therapy.

PMID- 22138743
TI  - [Automatic feeding systems for horses in group housing systems with regard to
      animal welfare. Part 2: Comparison of different automatic feeding systems].
AB  - OBJECTIVE: Comparison with regard to animal welfare of different automatic
      feeding systems for hay and concentrate in group housing systems for horses using
      parameters of ethology and physiology. MATERIAL AND METHODS: Parameters of
      research comprised: duration of stay, frequency of visit, threatening behaviour
      with and without risk of injury, and avoiding behaviour as well as heart rate and
      injuries of the integument. 452 horses were observed at the feeding area of 32
      run-out-sheds. Every group of horses was continuously observed following the pie
      chart system for 24 hours. RESULTS: The "walk-through" station significantly
      reduced the number of conflicts in the feeding area, whereas those systems which
      are appropriate for the feeding horses (feeding station with access barrier and
      without stimulation device by electric shock) led to a higher frequency of visits
      and a longer duration of stay resulting in more threatening gestures. However,
      the number of negative interactions in the feeding area of the feeding systems
      can all together be classified as relatively insignificant. The heart rate was
      within the physiological range (45.1 +/- 12.42 beats/min) in the waiting area,
      but increased by approximately 20 beats/min on average within the feeding
      station. Some horses showed a very high heart rate (>= 100 beats/min) while
      entering the feeding station, possibly stress-related. There were no injuries of
      the integument associated with the feeding systems. The most important factor of
      the observation criteria was the individual group housing system with its
      different dimensions, conception and management. CONCLUSION: "Walk-through"
      stations are better than "walk-back" stations with regard to animal welfare.
      Likewise, automatic feeding stations with a current-carrying stimulation device
      are not supportive of good welfare. The other differences between the
      constructions of feeding stations of present systems are probably of less
      importance, particularly as it was shown that the stable (management, stable
      area, conception) had a significant influence on the surveyed parameters.
      Investigations to obtain information on the cause for the sporadic occurrence of
      very high heart rate values should be undertaken.

PMID- 22138744
TI  - Diagnosis of internal and external hydrocephalus in a warmblood foal using
      magnetic resonance imaging.

PMID- 22138745
TI  - Rupture of the prepubic tendon in a congenitally lordotic mare.

PMID- 22138746
TI  - [Haematologic parameters in goats].

PMID- 22138747
TI  - Melatonin pathway genes and breast cancer risk among Chinese women.
AB  - Previous studies suggest that melatonin may act on cancer growth through a
      variety of mechanisms, most notably by direct anti-proliferative effects on
      breast cancer cells and via interactions with the estrogen pathway. Three genes
      are largely responsible for mediating the downstream effects of melatonin:
      melatonin receptors 1a and 1b (MTNR1a and MTNR1b), and arylalkylamine N
      acetyltransferase (AANAT). It is hypothesized that genetic variation in these
      genes may lead to altered protein production or function. To address this
      question, we conducted a comprehensive evaluation of the association between
      common single nucleotide polymorphisms (SNPs) in the MTNR1a, MTNR1b, and AANAT
      genes and breast cancer risk among 2,073 cases and 2,083 controls, using a two
      stage analysis of genome-wide association data among women of the Shanghai Breast
      Cancer Study. Results demonstrate two SNPs were consistently associated with
      breast cancer risk across both study stages. Compared with MTNR1b rs10765576
      major allele carriers (GG or GA), a decreased risk of breast cancer was
      associated with the AA genotype (OR = 0.78, 95% CI = 0.62-0.97, P = 0.0281).
      Although no overall association was seen in the combined analysis, the effect of
      MTNR1a rs7665392 was found to vary by menopausal status (P-value for interaction
      = 0.001). Premenopausal women with the GG genotype were at increased risk for
      breast cancer compared with major allele carriers (TT or TG) (OR = 1.57, 95% CI =
      1.07-2.31, P = 0.020), while postmenopausal women were at decreased risk (OR =
      0.58, 95% 0.36-0.95, P = 0.030). No significant breast cancer associations were
      found for variants in the AANAT gene. These results suggest that common genetic
      variation in the MTNR1a and 1b genes may contribute to breast cancer
      susceptibility, and that associations may vary by menopausal status. Given that
      multiple variants in high linkage disequilibrium with MTNR1b rs76653292 have been
      associated with altered function or expression of insulin and glucose family
      members, further research may focus on clarifying this relationship.

PMID- 22138748
TI  - Phase 2 study of neoadjuvant treatment with NOV-002 in combination with
      doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2
      negative clinical stage II-IIIc breast cancer.
AB  - NOV-002 (a formulation of disodium glutathione disulfide) modulates signaling
      pathways involved in tumor cell proliferation and metastasis and enhances anti
      tumor immune responsiveness in tumor models. The addition of NOV-002 to
      chemotherapy has been shown to increase anti-tumor efficacy in animal models and
      some early phase oncology trials. We evaluated the clinical effects of NOV-002 in
      primary breast cancer, whether adding NOV-002 to standard preoperative
      chemotherapy increased pathologic complete response rates (pCR) at surgery, and
      determined whether NOV-002 mitigated hematologic toxicities of chemotherapy and
      whether levels of myeloid derived suppressor cells (MDSC) were predictive of
      response. Forty-one women with newly diagnosed stages II-IIIc HER-2 negative
      breast cancer received doxorubicin-cyclophosphamide followed by docetaxel (AC ->
      T) every 3 weeks and concurrent daily NOV-002 injections. The trial was powered
      to detect a doubling of pCR rate from 16 to 32% with NOV-002 plus AC -> T (alpha
      = 0.05, beta = 80%). Weekly complete blood counts were obtained as well as
      circulating MDSC levels on day 1 of each cycle were quantified. Of 39 patients
      with 40 evaluable tumors, 15 achieved a pCR (38%), meeting the primary endpoint
      of the trial. Concurrent NOV-002 resulted in pCR rates for AC -> T chemotherapy
      higher than previously reported. Patients with lower levels of circulating MDSCs
      at baseline and on the last cycle of chemotherapy had significantly higher
      probability of a pCR (P = 0.02). Further evaluation of NOV-002 in a randomized
      study is warranted.

PMID- 22138749
TI  - Revisiting the role of hCG: new regulation of the angiogenic factor EG-VEGF and
      its receptors.
AB  - Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an
      angiogenic factor reported to be specific for endocrine tissues, including the
      placenta. Its biological activity is mediated via two G protein-coupled
      receptors, prokineticin receptor 1 (PROKR1) and prokineticin receptor 2 (PROKR2).
      We have recently shown that (i) EG-VEGF expression peaks between the 8th and 11th
      weeks of gestation, (ii) its mRNA and protein levels are up-regulated by hypoxia,
      (iii) EG-VEGF is a negative regulator of trophoblast invasion and (iv) its
      circulating levels are increased in preeclampsia (PE), the most threatening
      pathology of pregnancy. Here, we investigated the regulation of the expression of
      EG-VEGF and its receptors by hCG, a key pregnancy hormone that is also
      deregulated in PE. During the first trimester of pregnancy, hCG and EG-VEGF
      exhibit the same pattern of expression, suggesting that EG-VEGF is potentially
      regulated by hCG. Both placental explants (PEX) and primary cultures of
      trophoblasts from the first trimester of pregnancy were used to investigate this
      hypothesis. Our results show that (i) LHCGR, the hCG receptor, is expressed both
      in cyto- and syncytiotrophoblasts, (ii) hCG increases EG-VEGF, PROKR1 and PROKR2
      mRNA and protein expression in a dose- and time-dependent manner, (iii) hCG
      increases the release of EG-VEGF from PEX conditioned media, (iv) hCG effects are
      transcriptional and post-transcriptional and (v) the hCG effects are mediated by
      cAMP via cAMP response elements present in the EG-VEGF promoter region.
      Altogether, these results demonstrate a new role for hCG in the regulation of EG
      VEGF and its receptors, an emerging regulatory system in placental development.

PMID- 22138751
TI  - Reversible cell-cycle entry in adult kidney podocytes through regulated control
      of telomerase and Wnt signaling.
AB  - Mechanisms of epithelial cell renewal remain poorly understood in the mammalian
      kidney, particularly in the glomerulus, a site of cellular damage in chronic
      kidney disease. Within the glomerulus, podocytes--differentiated epithelial cells
      crucial for filtration--are thought to lack substantial capacity for
      regeneration. Here we show that podocytes rapidly lose differentiation markers
      and enter the cell cycle in adult mice in which the telomerase protein component
      TERT is conditionally expressed. Transgenic TERT expression in mice induces
      marked upregulation of Wnt signaling and disrupts glomerular structure, resulting
      in a collapsing glomerulopathy resembling those in human disease, including HIV
      associated nephropathy (HIVAN). Human and mouse HIVAN kidneys show increased
      expression of TERT and activation of Wnt signaling, indicating that these are
      general features of collapsing glomerulopathies. Silencing transgenic TERT
      expression or inhibiting Wnt signaling through systemic expression of the Wnt
      inhibitor Dkk1 in either TERT transgenic mice or in a mouse model of HIVAN
      results in marked normalization of podocytes, including rapid cell-cycle exit, re
      expression of differentiation markers and improved filtration barrier function.
      These data reveal an unexpected capacity of podocytes to reversibly enter the
      cell cycle, suggest that podocyte renewal may contribute to glomerular
      homeostasis and implicate the telomerase and Wnt-beta-catenin pathways in
      podocyte proliferation and disease.

PMID- 22138752
TI  - Key contribution of CPEB4-mediated translational control to cancer progression.
AB  - Malignant transformation, invasion and angiogenesis rely on the coordinated
      reprogramming of gene expression in the cells from which the tumor originated.
      Although deregulated gene expression has been extensively studied at genomic and
      epigenetic scales, the contribution of the regulation of mRNA-specific
      translation to this reprogramming is not well understood. Here we show that
      cytoplasmic polyadenylation element binding protein 4 (CPEB4), an RNA binding
      protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation,
      is overexpressed in pancreatic ductal adenocarcinomas and glioblastomas, where it
      supports tumor growth, vascularization and invasion. We also show that, in
      pancreatic tumors, the pro-oncogenic functions of CPEB4 originate in the
      translational activation of mRNAs that are silenced in normal tissue, including
      the mRNA of tissue plasminogen activator, a key contributor to pancreatic ductal
      adenocarcinoma malignancy. Taken together, our results document a key role for
      post-transcriptional gene regulation in tumor development and describe a detailed
      mechanism for gene expression reprogramming underlying malignant tumor
      progression.

PMID- 22138753
TI  - In vivo imaging of ligand receptor binding with Gaussia luciferase
      complementation.
AB  - Studies of ligand-receptor binding and the development of receptor antagonists
      would benefit greatly from imaging techniques that translate directly from cell
      based assays to living animals. We used Gaussia luciferase protein fragment
      complementation to quantify the binding of chemokine (C-X-C motif) ligand 12
      (CXCL12) to chemokine (C-X-C motif) receptor 4 (CXCR4) and CXCR7. Studies
      established that small-molecule inhibitors of CXCR4 or CXCR7 specifically blocked
      CXCL12 binding in cell-based assays and revealed differences in kinetics of
      inhibiting chemokine binding to each receptor. Bioluminescence imaging showed
      CXCL12-CXCR7 binding in primary and metastatic tumors in a mouse model of breast
      cancer. We used this imaging technique to quantify drug-mediated inhibition of
      CXCL12-CXCR4 binding in living mice. We expect this imaging technology to advance
      research in areas such as ligand-receptor interactions and the development of new
      therapeutic agents in cell-based assays and small animals.

PMID- 22138754
TI  - PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin
      production in stromal cells.
AB  - The platelet-derived growth factor (PDGF) signaling system contributes to tumor
      angiogenesis and vascular remodeling. Here we show in mouse tumor models that
      PDGF-BB induces erythropoietin (EPO) mRNA and protein expression by targeting
      stromal and perivascular cells that express PDGF receptor-beta (PDGFR-beta).
      Tumor-derived PDGF-BB promoted tumor growth, angiogenesis and extramedullary
      hematopoiesis at least in part through modulation of EPO expression. Moreover,
      adenoviral delivery of PDGF-BB to tumor-free mice increased both EPO production
      and erythropoiesis, as well as protecting from irradiation-induced anemia. At the
      molecular level, we show that the PDGF-BB-PDGFR-bbeta signaling system activates
      the EPO promoter, acting in part through transcriptional regulation by the
      transcription factor Atf3, possibly through its association with two additional
      transcription factors, c-Jun and Sp1. Our findings suggest that PDGF-BB-induced
      EPO promotes tumor growth through two mechanisms: first, paracrine stimulation of
      tumor angiogenesis by direct induction of endothelial cell proliferation,
      migration, sprouting and tube formation, and second, endocrine stimulation of
      extramedullary hematopoiesis leading to increased oxygen perfusion and protection
      against tumor-associated anemia.

PMID- 22138757
TI  - Frequency of HLA-DP-specific antibodies and a possible new cross-reacting group.
AB  - Clinical studies have demonstrated that HLA-DP-specific antibodies can be
      detrimental to a transplanted kidney. The number of patients affected is
      proportional to the frequency of DP antibodies. We determined the frequency of
      HLA-DP-specific antibodies en toto and in the absence of cross-reactive DR
      antibodies. Of 650 waitlisted renal patients, 271 (42%) were reactive with HLA-DP
      antigens in solid-phase immunoassays. Of these 271 sera, 58 (21%) were negative
      for reactivity with cross-reactive DR antigens, and 16 (5.9%) had no class II
      antibody other than DP. Eliminating sera containing DR cross-reactive antibodies
      reduced the frequency but not the overall strength of DP antibodies. Although
      most DP antibodies were not expected to yield a positive cytotoxicity crossmatch,
      2 DP-specific antibodies yielded cytotoxic crossmatch tests with titers of >512.
      The occurrence of HLA-DP-specific antibody differed significantly between
      previously transplanted (62%) and nontransplanted (38%) patients, but no
      difference was observed among patients categorized by race or sex. One serum
      demonstrated strong cross-reactivity between DP and DRB1*01:03 in the absence of
      DR1 or DR11 reactivity. Sequence alignments were performed and a possible new
      cross-reactivity between DRB1*01:03 and DP2, DP9, DP10, DP13, DP16, and DP17 was
      defined. Two additional sera confirmed this cross-reactivity.

PMID- 22138756
TI  - Ion release from magnesium materials in physiological solutions under different
      oxygen tensions.
AB  - Although magnesium as degradable biomaterial already showed clinical proof of
      concepts, the design of new alloys requires predictive in vitro methods, which
      are still lacking. Incubation under cell culture conditions to obtain
      "physiological" corrosion may be a solution. The aim of this study was to analyse
      the influence of different solutions, addition of proteins and of oxygen
      availability on the corrosion of different magnesium materials (pure Mg, WE43,
      and E11) with different surface finishing. Oxygen content in solution, pH,
      osmolality and ion release were determined. Corrosion led to a reduction of
      oxygen in solution. The influence of oxygen on pH was enhanced by proteins, while
      osmolality was not influenced. Magnesium ion release was solution-dependent and
      enhanced in the initial phase by proteins with delayed release of alloying
      elements. The main corrosion product formed was magnesium carbonate. Therefore,
      cell culture conditions are proposed as first step toward physiological
      corrosion.

PMID- 22138759
TI  - Catalytic asymmetric construction of tetrasubstituted carbon stereocenters by
      conjugate addition of dialkyl phosphine oxides to beta,beta-disubstituted
      alpha,beta-unsaturated carbonyl compounds.
AB  - The catalytic asymmetric phospha-Michael reaction of dialkyl phosphine oxides
      with beta,beta-disubstituted alpha,beta-unsaturated carbonyl compounds was
      achieved. The products bearing tetrasubstituted carbon stereocenters were
      obtained in high yields with excellent enantioselectivities (up to >99% ee).

PMID- 22138760
TI  - Retrospective review of 50 eyes with long-term silicone oil tamponade for more
      than 12 months.
AB  - BACKGROUND: Silicone oil (SO) is an established tamponade in treating complex
      vitreoretinal diseases. Although SO is intended to be removed after several weeks
      to months, permanent SO might be unavoidable in a small subgroup of patients with
      an extremely complicated clinical course. The aim of this study is to describe
      the long-term effects of intraocular SO tamponade. METHODS: This retrospective
      study included 50 patients with intraocular SO (Oxane 5700 Bausch & Lomb,
      Kingston-upon-Thames, UK) for at least 12 months. The most common reasons for
      long-term SO tamponade were: retinal re-detachment (re-RD), proliferative
      diabetic retinopathy (PDR), ocular trauma, and persistent hypotony. RESULTS: Mean
      age was 59.2 +/- 18.4 years, and mean duration of silicone oil in the eye was
      54.5 +/- 58.6 months (median, 30 months). The average number of previous
      surgeries were 2.2 +/- 1.5. Anatomic success was achieved in 37/50 (74%) of
      patients. Visual acuities (logMAR) were 1.8 +/- 0.6, 1.6 +/- 0.6, 2 +/- 0.7 and
      intraocular pressures (mmHg) were 15.6 +/- 7, 15.7 +/- 5.5, 16.5 +/- 7.1 at 3
      months, 1 year and at last follow-up respectively. The main long-term silicone
      oil-related complications observed were: band keratopathy (8%), corneal
      decompensation (12%), iris rubeosis (14%), and optic neuropathy (28%). Forty
      percent of patients achieved ambulatory vision in the SO-filled eye at final
      follow-up. CONCLUSION: Long-term silicone oil can be a last-resort option in
      selected patients with severe vitreoretinal disease. Anterior and posterior
      segment complications did occur at significant rates. Forty percent of our
      patients maintained ambulatory vision. The actual number of patients that
      achieved satisfactory stereopsis and benefited functionally from long-term SO was
      much less [7/50 (14%)].

PMID- 22138758
TI  - Effects of vitamin E ingestion on plasma and urinary risk factors for calcium
      oxalate urolithiasis in two population groups having different stone-risk
      profiles: evidence of different physiological handling mechanisms.
AB  - It has been demonstrated that vitamin E supplementation reduces calciuria and
      oxaluria and that it may also prevent oxalate-mediated peroxidative injury, all
      of which reduce the risk of calcium oxalate urolithiasis. In view of the
      significant difference in stone occurrence in black (B) and white (W) South
      Africans, we undertook to investigate the effects of vitamin E supplementation in
      subjects from these two groups. Five healthy males from each group ingested one
      capsule (400 IU) of vitamin E daily for 60 days. Blood and 24 h urine samples
      were collected at baseline and on day 60; 24 h dietary questionnaires were
      simultaneously completed. Urine composition was determined by routine analyses.
      Urinary and plasma TBARS were determined using a commercially available assay kit
      while plasma vitamin E was determined by reverse phase HPLC. Plasma vitamin E
      increased significantly in W but not in B. Urinary and plasma TBARS did not
      increase in either group. Urinary citrate increased significantly in both groups
      but the percentage increase in W (169%) was greater than that in B (82%). No
      other urinary parameter changed significantly. The increase in plasma vitamin E
      in W but not in B suggests either that the mechanism by which it is packaged into
      chylomicrons, which are secreted into the systemic circulation, is suppressed in
      the latter group or that it is differentially absorbed in the two groups.
      Similarly, to explain the greater increase in citraturia in W compared to B, we
      speculate that inhibition of lipogenesis of arachidonic acid by vitamin E,
      ultimately leading to an increase in citraturia, occurs to a lesser extent in B
      than in W.

PMID- 22138761
TI  - Incidental finding of sclerosing angiomatoid nodular transformation of the
      spleen.
AB  - BACKGROUND: The prevalence of tumors in the spleen is rare; most tumors are
      benign and of vascular origin. In 2004 a vascular lesion was first described, the
      sclerosing angiomatoid nodular transformation (SANT), which is a benign lesion
      with good circumscription and multinodular angiomatoid appearance. We report a
      case of this rare tumor in the spleen which was incidentally found in a patient
      with a tumorous lesion in the pancreatic tail. CASE REPORT: A 69-year-old patient
      was referred to our hospital with a tumor in the pancreatic tail which was
      suspicious for cancer. Radiologic work-up revealed furthermore a 4 cm in diameter
      large lesion central in the spleen suspicious for metastasis of the pancreatic
      tumor. The patient underwent surgery and a distal pancreatectomy with splenectomy
      was performed. Histologic specimen obtained a sclerosing angiomatoid nodular
      transformation in the spleen. The operative and postoperative course was
      uneventful. CONCLUSIONS: SANT of the spleen are very rare tumors and should be
      considered as an important differential diagnosis to other vascular lesions.

PMID- 22138762
TI  - Epidemiological and economic aspects of polytrauma management in Austria.
AB  - INTRODUCTION: In Austria, treatment of multiple trauma patients has developed
      into an established nationwide trauma center specialty with its own unique
      identity. Although it represents a substantial financial investment, it ensures
      supply at international standards. The question of whether multiple trauma
      patients should be treated only in specialized trauma centers or in several
      hospitals remains controversial on both national and international grounds. The
      aim of this study was to assess Austrian trauma departments for international
      comparison. MATERIAL AND METHODS: We performed a survey of all 54 Austrian trauma
      departments by collecting data through questionnaires. The number of staff,
      potential of infrastructure, and treatment strategies were obtained. RESULTS:
      93.3% of the trauma departments responded to the questionnaires. In level I
      trauma centers the amount of trauma beds reached 11% of the total bed capacity,
      13% in level II, and 18% in level III units. Level I centers showed an average of
      35% of intensive care beds for trauma patients. 53% and 51% were the proportions
      for level II and III centers. Level I hospitals displayed an average of 28.3
      trauma surgeons, while level II and III units had less doctors at their disposal
      in the trauma departments. On average, 94% of the patients arrived by emergency
      medical support at the hospital. 94% of the trauma departments used chest tubes,
      70% performed craniotomies and neurovascular reconstruction. 33% of the centers
      were equipped to perform replantations. DISCUSSION: The data demonstrate the
      broad spectrum of polytrauma treatment in Austrian trauma centers. The discussed
      need for centralization of polytrauma care cannot be justified based on these
      data. Limiting from a medical perspective, however, is the lacking comparability
      of quality of care due to the currently missing objective quality criteria.

PMID- 22138763
TI  - Classification of follicular lymphoma images: a holistic approach with symbol
      based machine learning methods.
AB  - It is not very often to see a symbol-based machine learning approach to be used
      for the purpose of image classification and recognition. In this paper we will
      present such an approach, which we first used on the follicular lymphoma images.
      Lymphoma is a broad term encompassing a variety of cancers of the lymphatic
      system. Lymphoma is differentiated by the type of cell that multiplies and how
      the cancer presents itself. It is very important to get an exact diagnosis
      regarding lymphoma and to determine the treatments that will be most effective
      for the patient's condition. Our work was focused on the identification of
      lymphomas by finding follicles in microscopy images provided by the Laboratory of
      Pathology in the University Hospital of Tenerife, Spain. We divided our work in
      two stages: in the first stage we did image pre-processing and feature
      extraction, and in the second stage we used different symbolic machine learning
      approaches for pixel classification. Symbolic machine learning approaches are
      often neglected when looking for image analysis tools. They are not only known
      for a very appropriate knowledge representation, but also claimed to lack
      computational power. The results we got are very promising and show that symbolic
      approaches can be successful in image analysis applications.

PMID- 22138764
TI  - A DNA barcode library for Korean Chironomidae (Insecta: Diptera) and indexes for
      defining barcode gap.
AB  - Non-biting midges (Diptera: Chironomidae) are a diverse population that commonly
      causes respiratory allergies in humans. Chironomid larvae can be used to indicate
      freshwater pollution, but accurate identification on the basis of morphological
      characteristics is difficult. In this study, we constructed a mitochondrial
      cytochrome c oxidase subunit I (COI)-based DNA barcode library for Korean
      chironomids. This library consists of 211 specimens from 49 species, including
      adults and unidentified larvae. The interspecies and intraspecies COI sequence
      variations were analyzed. Sophisticated indexes were developed in order to
      properly evaluate indistinct barcode gaps that are created by insufficient
      sampling on both the interspecies and intraspecies levels and by variable
      mutation rates across taxa. In a variety of insect datasets, these indexes were
      useful for re-evaluating large barcode datasets and for defining COI barcode
      gaps. The COI-based DNA barcode library will provide a rapid and reliable tool
      for the molecular identification of Korean chironomid species. Furthermore, this
      reverse-taxonomic approach will be improved by the continuous addition of other
      speceis' sequences to the library.

PMID- 22138765
TI  - Selection and characterization of tenascin C targeting peptide.
AB  - Since tenascin C is a factor expressed highly in the tumor-associated matrix, it
      would be a desirable first step for targeting the tumor-specific
      microenvironment. In fact, a high level of tenascin C expression has been
      reported in most solid tumors, including lung cancer, colon cancer and
      glioblastoma. Therefore, the targeted binding of tenascin C in tumor stroma would
      inhibit tumor metastasis by modulating cancer cell growth and migration. We
      isolated a peptide that bound to tenascin C by phage display peptide library
      selection, and the selected peptide specifically recognized tenascin C protein in
      xenograft mouse tissue. We also observed exclusive staining of tenascin C by the
      selected peptide in tumor patient tissues. Moreover, the peptide reduced tenascin
      C-induced cell rounding and migration. We propose that the tenascin C targeting
      peptide may be useful as a specific anti-cancer diagnostic and therapeutic tool
      for most human solid tumors.

PMID- 22138767
TI  - [Colonization of the teat skin and the teat canal of lactating dairy cattle by
      mastitis pathogens].
AB  - OBJECTIVE: The teat canal of lactating dairy cattle is the first barrier against
      mastitis pathogens invading the teat cistern and the udder lumen. However, in
      several studies it could be shown that the teat skin and the teat canal
      epithelium are colonized by mainly staphylococci as well as by other pathogenic
      or facultative pathogenic micro-organisms. The aim of the study was to evaluate
      the pathogen pressure on the bovine mammary gland and to establish data on the
      prevalence of relevant micro-organisms. MATERIAL AND METHODS: In 32 randomly
      selected German dairy farms the colonization of the teat skin and the teat canal
      by S.aureus (Baird Parker agar), Sc.uberis (modified Rambach agar according to
      Watts et al. [1993]), enterococci (kanamycin esculin azide agar) and coliforms
      (ChromoCult Coliform agar) was investigated by the wet/dry swab technique
      DIN10113-1:1997-07. RESULTS: In total 84.5% of all 1358 investigated teat canals
      of clinically healthy cattle were colonized by at least one of the four pathogen
      groups. S.aureus was isolated from 72.2% of the teat canals. For S.aureus ,
      Sc.uberis and E.coli maximum bacterial counts of >10(6) cfu/swab and for other
      coliform bacteria>10(7) cfu/swab were detected. Correlations could be found
      between the bacterial counts on the teat skin and in the teat canal within the
      pathogen groups S.aureus, Sc.uberis, E.coli and other coliforms (Spearman's rank
      correlation coefficient r>=0.30, p<0.001) as well as between the environmental
      udder pathogens Sc.uberis and coliforms (r>=0.25, p<0.01). CONCLUSION AND
      CLINICAL RELEVANCE: The variation of the bacterial counts on teat epithelia could
      be an indicator that the microflora of the teat canal epithelium can be affected
      by management practices in dairy farms. The results of this study point out that
      under field conditions the efficiency of hygienic practices (husbandry, milking)
      can be assessed by sampling of the bovine teat canal by the wet/dry swab
      technique.

PMID- 22138766
TI  - Unresolved antiretroviral treatment management issues in HIV-infected children.
AB  - Antiretroviral therapy in children has expanded dramatically in low-income and
      middle-income countries. The World Health Organization revised its pediatric HIV
      guidelines to recommend initiation of antiretroviral therapy in all HIV-infected
      children younger than 2 years, regardless of CD4 count or clinical stage. The
      number of children starting life-long antiretroviral therapy should therefore
      expand dramatically over time. The early initiation of antiretroviral therapy has
      indisputable benefits for children, but there is a paucity of definitive
      information on the potential adverse effects. In this review, a comprehensive
      literature search was conducted to provide an overview of our knowledge about the
      complications of treating pediatric HIV. Antiretroviral therapy in children, as
      in adults, is associated with enhanced survival, reduction in opportunistic
      infections, improved growth and neurocognitive function, and better quality of
      life. Despite antiretroviral therapy, HIV-infected children may continue to lag
      behind their uninfected peers in growth and development. In addition, epidemic
      concurrent conditions, such as tuberculosis, malaria, and malnutrition, can
      combine with HIV to yield more rapid disease progression and poor treatment
      outcomes. Additional studies are required to evaluate the long-term effects of
      antiretroviral therapy in HIV-infected infants, children, and adolescents,
      particularly in resource-limited countries where concomitant infections and
      conditions may enhance the risk of adverse effects. There is an urgent need to
      evaluate drug-drug interactions in children to determine optimal treatment
      regimens for both HIV and coinfections.

PMID- 22138768
TI  - [Evaluation of bacteriological diagnosis in secretions of clinical mastitis cases
      with PetrifilmTM in the veterinary practice laboratory].
AB  - OBJECTIVE: Especially in cases of clinical mastitis a rapid test for
      identification of responsible pathogens would be useful for choosing the
      appropriate treatment. The objective of the study was to determine whether two
      rapid tests are suitable to detect infections with coliforms and Staphylococcus
      aureus, respectively, in cows with acute mastitis under field conditions.
      MATERIAL AND METHODS: The evaluated tests were "PetrifilmTM Rapid Coliform" and
      "PetrifilmTM Staph Express Count System". A total of n=107 double, quarter
      foremilk samples from dairy cows with clinical signs of acute mastitis was
      obtained aseptically. All samples were examined microbiologically by means of
      both conventional methods and using both PetrifilmTM tests. RESULTS: Overall
      sensitivity for the PetrifilmTM tests was 32%, overall specificity 90%, and the
      positive predictive value 24%. In contrast, conventional methods yielded positive
      results in only 18% of cases, meaning that with the petrifilm kits, 3.5 times
      more infections caused by coliforms could be detected. However, not all coliforms
      cultivated conventionally were also identified by the PetrifilmTM tests.
      CONCLUSION AND CLINICAL RELEVANCE: These unsatisfactory results may be due to
      flaws in the conventional culturing or contamination of samples. Therefore, the
      results of this field trial do not lead to a conclusive evaluation of this
      diagnostic device under field conditions, although the PetrifilmTM test for
      coliforms may already be recommended to identify infections caused by gram
      negative microorganisms. Once caution is taken at sampling, this kit may lead to
      a basic decision regarding therapy.

PMID- 22138769
TI  - Laboratory diagnostics in the urine of young and pregnant ewes.
AB  - OBJECTIVE: The purpose of this study was to identify values for net acid base
      excretion (NABE) which are significant indicators of the acid-base equilibrium in
      pregnant and young ewes and to show its relationship with other parameters (base,
      acid, ammonium [NH4], base-acid quotient, sodium [Na], potassium [K], calcium
      [Ca]) in ovine urine. In contrast to dairy cows, data are rare on these
      parameters in ewes. MATERIAL AND METHODS: A total of 99 animals were used in the
      study, consisting of 56 young (average of 5.6+/-1.1 months) and 43 pregnant ewes
      (average of 35.2+/-18.8 months). Measurement of fractional NABE in urine samples
      was carried out according to the method reported by Kutas. The pH value of the
      urine was measured with a laboratory pH meter. Na, K and total Ca were measured
      with a flame photometer. RESULTS: For all values except Na significant
      differences occurred between urine samples of pregnant ewes and young ewes
      (p<0.001). Base, acid, NH4, NABE, K and Ca values were significantly higher in
      the urine of the youngs than in pregnant ewes. In young ewes, a strong
      correlation was found between NABE and base values while a weak correlation could
      be observed between pH and base values. In pregnant ewes, strong NABE-base, NABE
      K, K-acid and K-base correlations were found as well as weak NH4-base, NH4-NABE
      and NH4-K correlations. There was a strongly positive correlation between NABE
      and NH4 in pregnant ewes, while a weak negative correlation between those values
      was observed in young ewes. CONCLUSION: For the first time, we established values
      for NABE and certain other parameters in urine of pregnant ewes and young ewes.
      It was shown that the acid-base balance in pregnant ewes and young ewes can be
      evaluated by measuring NABE and certain trace elements in urine like in cattle.

PMID- 22138771
TI  - On-farm udder health monitoring.
AB  - In this article an on-farm monitoring approach on udder health is presented.
      Monitoring of udder health consists of regular collection and analysis of data
      and of the regular evaluation of management practices. The ultimate goal is to
      manage critical control points in udder health management, such as hygiene, body
      condition, teat ends and treatments, in such a way that results (udder health
      parameters) are always optimal. Mastitis, however, is a multifactorial disease,
      and in real life it is not possible to fully prevent all mastitis problems.
      Therefore udder health data are also monitored with the goal to pick up
      deviations before they lead to (clinical) problems. By quantifying udder health
      data and management, a farm is approached as a business, with much attention for
      efficiency, thought over processes, clear agreements and goals, and including
      evaluation of processes and results. The whole approach starts with setting SMART
      (Specific, Measurable, Acceptable, Realistic, Time-bound) goals, followed by an
      action plan to realize these goals.

PMID- 22138770
TI  - [Risk-based monitoring of udder health. A review].
AB  - Monitoring udder health of a dairy herd has three functions: firstly describing
      the actual situation, secondly evaluating the efficiency of adopted improvement
      measures and treatments, thirdly to detect emerging problems as early as
      possible. Therefore, husbandry, feeding, and management of the cows have to be
      included in the surveillance. Risk-based monitoring of the udder health is
      characterized on the one hand by focussing on the currently relevant herd
      specific risk factors. Consequently, it is a dynamic process. On the other hand,
      it is affected by a clearly structured approach to prevent a loss of control due
      to a lack of attention in any area. All essential decisions and actions are
      documented to be comprehensible and available for critical examination. This
      review explains the procedure to establish a risk-based monitoring program on
      dairy farms.

PMID- 22138772
TI  - [Terminology for classifying the porcine reproductive and respiratory syndrome
      virus (PRRSV) status of swine herds].
AB  - Standardized terminology for the porcine reproductive and respiratory syndrome
      virus (PRRSV) status of swine herds is necessary to facilitate communication
      between veterinarians, swine producers, genetic companies, and other industry
      participants. It is also required for implementation of regional and national
      efforts towards PRRSV control and elimination. The purpose of this paper is to
      provide a herd classification system for describing the PRRSV status of herds,
      based upon a set of definitions reflecting the biology and ecology of PRRSV. The
      herd classification system was developed by a definitions committee formed
      jointly by the American Association of Swine Veterinarians (AASV) and the United
      States Department of Agriculture PRRS-Coordinated Agricultural Project, and was
      approved by the AASV Board of Directors on March 9, 2010. The committee included
      veterinarians from private practice and industry, researchers, and
      representatives from AASV and the National Pork Board. Breeding herds, with or
      without growing pigs on the same premises, are categorized as Positive Unstable
      (Category I), Positive Stable (Category II), Provisional Negative (Category III),
      or Negative (Category IV) on the basis of herd shedding and exposure status.
      Growing-pig herds are categorized as Positive or Negative. Recommended testing
      procedures and decision rules for herd classification are detailed.

PMID- 22138773
TI  - [Hypospadias in a Friesian foal. A case report].

PMID- 22138774
TI  - [Use of local anaesthetics in the horse. Pharmacological and legal aspects].

PMID- 22138776
TI  - Expression of osteoprotegerin and receptor activator of nuclear factor kappaB
      ligand in root resorption induced by heavy force in rats.
AB  - OBJECTIVE: The aim of this study was to investigate the expression patterns of
      osteoprotegerin (OPG) and the receptor activator of nuclear factor kappaB ligand
      (RANKL) in root resorption during orthodontic tooth movement. MATERIAL AND
      METHODS: Forty 12-week-old male SD rats were used with the right maxillary side
      as the experimental group and the left maxillary side as the control group. After
      1 N (100g) force was loaded on the right maxillary first molar, the rats were
      sacrificed on days 0, 1, 4, 8, and 12. Mesial root resorption of the first molar,
      the number of odontoclasts and osteoclasts, and OPG and RANKL mRNA expression
      were determined by hematoxylin-eosin and scanning electron microscopy, tartrate
      resistant acid phosphate staining, and in situ hybridization, respectively.
      RESULTS: Serious root resorption was apparent on the pressure side of the mesial
      root of the right maxillary first molar on days 8 and 12. The number of
      odontoclasts in the cementum lacuna was elevated on days 8 and 12. OPG expression
      rose significantly on the tensile side, while RANKL expression increased on the
      pressure side. The mRNA level of RANKL was significantly elevated on days 4, 8,
      and 12. Moreover, the RANKL/OPG mRNA ratio was increased on the pressure side,
      but decreased on the tensile side. CONCLUSION: Changes in the expression of RANKL
      mRNA and the RANKL/OPG mRNA ratio are accompanied by a parallel alteration in the
      number of odontoclasts and tooth resorption, suggesting crucial involvement of
      RANKL and OPG in tooth resorption.

PMID- 22138779
TI  - Inappropriate gene expression in human cancer and its far-reaching biological and
      clinical significance.
AB  - This article provides a broad overview of the field of inappropriate gene
      expression in many organisms across the animal and plant kingdoms as well as its
      importance to human disease in general and cancer in particular. Study of the
      topic is especially important for understanding how the chaotic maelstrom of
      evolving and cascading regulatory genetic interactions in an advancing cancer
      produces its clinical effects and for designing pragmatic solutions to how such
      disorder might eventually be tamed. It is emphasized that the topic warrants much
      more attention in research and in clinical practice because of the added value it
      brings to refining cancer diagnosis and treatment and to the assessment of
      prognostic markers. It is also particularly relevant to understanding the
      etiology and extensive clinical manifestations of paraneoplastic syndromes
      affecting multiple organs remote from the tumor and the treatment or amelioration
      of the substantial morbidity that they cause in cancer patients. More broadly,
      inappropriate expression can be caused by a number of mechanisms including
      mutations, rearrangements of the genome, and viral insertions and, under
      prolonged selection pressures, also has the potential to be an agent of
      evolutionary change.

PMID- 22138782
TI  - Biomechanical contribution of the rib cage to thoracic stability.
AB  - STUDY DESIGN: In vitro assessment of rib cage biomechanics in the region of true
      ribs with the ribs intact then sequentially resected in 5 steps. OBJECTIVE: To
      determine the contribution of the rib cage to thoracic spine stability and
      kinematics. SUMMARY OF BACKGROUND DATA: Previous in vitro studies of rib cage
      biomechanics have used animal spines or human cadaveric spines with ribs left
      unsecured, limiting the ability of the ribs to contribute to stability. METHODS:
      Eight upper thoracic specimens that included 4 ribs and sternum were tested in
      special fixtures that disallowed relative movement of the distal ribs and their
      vertebrae. While applying 7.5 Nm pure moments in 3 planes, angular motion at the
      middle motion segment was studied in intact specimens and then (1) after
      splitting the sternum, (2) after removing the sternum, (3) after removing 50% of
      ribs, (4) after removing 75% of ribs, and (5) after disarticulating and
      completely removing ribs. RESULTS: During flexion/extension, the sternum and
      anterior rib cage most contributed to stability. During lateral bending, the
      posterior rib cage most contributed to stability. During axial rotation,
      stability was directly related to the proportion of ribs remaining intact. On
      average, intact ribs accounted for 78% of thoracic stability. An intact rib cage
      shifted the axis of rotation unpredictably, but its position remained consistent
      after partial resection of the ribs. During lateral bending, coupled axial
      rotation was mild and unaffected by ribs. CONCLUSION: Because of testing
      methodology, the rib cage accounted for a greater percentage of thoracic
      stability than previously estimated. Different rib cage structures resisted
      motion in different loading planes.

PMID- 22138783
TI  - The security analysis of transpedicular screw fixation in the lower cervical
      spine and a case report.
AB  - STUDY DESIGN: This study evaluated the anatomical parameters of the lower
      cervical spine by imaging methods and reported a case. OBJECTIVE: To explain low
      neurovascular injury rate and provide some suggestions in cervical transpedicular
      screw fixation (CTSF). SUMMARY OF BACKGROUND DATA: Because of anatomical
      complexity and possible severe complications, application of CTSF was limited.
      However, recent studies have indicated that although cervical pedicular screw
      perforations may happen, severe complications seldom occur. METHODS: In 20
      patients, several anatomical parameters were obtained on computed tomographic
      angiography (CTA) images of C3-C6, including the inner diameter of vertebral
      artery (d), the maximal width (A) and height (B) of the transverse foramen, the
      shortest distance between vertebral artery and cervical pedicle (h), and the
      angle between the longitudinal axis of pedicle and the hypothetical screw that
      just touches the vertebral artery (largest safe angle, LSA). Another 35 patients
      were chosen to measure the shortest distance between cervical pedicle and
      cervical spinal cord (H) and the angle between the longitudinal axis of pedicle
      and the hypothetical screw that just touches the cervical spinal cord (smallest
      angle, SA) on magnetic resonance imaging (MRI) of C4-C7. RESULTS: Between the
      left and the right sides, there was no statistically significant difference for
      d, A, B, h, and LSA at C3-C6 or H and SA at C4-C7. d, h, and H were,
      respectively, 3.97 +/- 0.65 mm, 0.89 +/- 0.44 mm, and 6.56 +/- 2.10 mm, and there
      was no statistically significant difference among C3-C6 for d and h or among C4
      C7 for H. LSA at C6 was larger than that at C3, C4, and C5; it increased from C5
      to C7. CONCLUSION: There was an "escaping space" for the vertebral artery and
      spinal cord. CTSF in the superior part of pedicle was relatively safer from
      accidental perforation of the vertebral artery than CTSF in the inferior part,
      and in C6 and C7, CTSF was safer from this injury than in C3, C4, and C5.

PMID- 22138781
TI  - Appropriateness of ambulatory prescriptions in Taiwan: translating claims data
      into initiatives.
AB  - BACKGROUND: Appropriate prescribing is fundamental to successful pharmacotherapy.
      The status of current ambulatory medication practices in medicine and pharmacy
      would be better understood through an analysis of community pharmacy prescription
      claims. OBJECTIVE: The aims of the study were to investigate patterns of the
      types of prescriptions claimed by community pharmacies, undetected prescription
      errors by community pharmacists, and associated factors of prescription errors.
      SETTING: A population-based claims database of prescriptions dispensed by
      community pharmacies in Taiwan. METHODS: Ambulatory prescriptions were randomly
      sampled and reassessed for prescribing appropriateness by medical center
      pharmacists using explicit criteria. Demographics of patients, physicians, care
      facilities, and prescription/dispensing details were assessed and used to
      identify associated factors for prescription errors using descriptive analyses as
      well as logistic regression. MAIN OUTCOME MEASURES: Erroneous prescriptions
      prescribed by physicians, and dispensed and claimed through community pharmacies.
      RESULTS: The study included analyses of 3065 prescriptions dispensed in community
      pharmacies resulting from 1003 patient visits, mostly to physician or dental
      clinics (99.5%). Prescribing characteristics, patterns, and examples of
      prescription errors are described. Prescription errors were identified in 18.3%
      (n = 560) of prescriptions and 34.9% (n = 350) of patient visits. Potential
      prescribing errors included errors of omission (25.5%), errors of commission
      (53.4%), and others (21.1%). The top three errors were incorrect dosage (27.5%),
      missing indication (23.6%), and insufficient or unavailable drug information
      (18.9%). Drugs most frequently associated with prescription errors included
      antihistamines, hormones, and gastrointestinal agents. Prescription were also
      higher in the central and eastern regions of Taiwan. Pediatricians accounted for
      a disproportionate number of prescription errors. CONCLUSION: Prescription errors
      are prevalent in ambulatory care in Taiwan, and differential practice standards
      exist between community and hospital services. This disparity needs to be
      reconciled by pertinent initiatives to enhance community-hospital and pharmacist
      general practitioner communication and interprofessional educational efforts to
      improve medication use and safety.

PMID- 22138778
TI  - Potential roles for prions and protein-only inheritance in cancer.
AB  - Inherited mutations are known to cause familial cancers. However, the cause of
      sporadic cancers, which likely represent the majority of cancers, is yet to be
      elucidated. Sporadic cancers contain somatic mutations (including oncogenic
      mutations); however, the origin of these mutations is unclear. An intriguing
      possibility is that a stable alteration occurs in somatic cells prior to
      oncogenic mutations and promotes the subsequent accumulation of oncogenic
      mutations. This review explores the possible role of prions and protein-only
      inheritance in cancer. Genetic studies using lower eukaryotes, primarily yeast,
      have identified a large number of proteins as prions that confer dominant
      phenotypes with cytoplasmic (non-Mendelian) inheritance. Many of these have
      mammalian functional homologs. The human prion protein (PrP) is known to cause
      neurodegenerative diseases and has now been found to be upregulated in multiple
      cancers. PrP expression in cancer cells contributes to cancer progression and
      resistance to various cancer therapies. Epigenetic changes in the gene expression
      and hyperactivation of MAP kinase signaling, processes that in lower eukaryotes
      are affected by prions, play important roles in oncogenesis in humans. Prion
      phenomena in yeast appear to be influenced by stresses, and there is considerable
      evidence of the association of some amyloids with biologically positive
      functions. This suggests that if protein-only somatic inheritance exists in
      mammalian cells, it might contribute to cancer phenotypes. Here, we highlight
      evidence in the literature for an involvement of prion or prion-like mechanisms
      in cancer and how they may in the future be viewed as diagnostic markers and
      potential therapeutic targets.

PMID- 22138784
TI  - Validation in Colombia of the Oswestry disability questionnaire in patients with
      low back pain.
AB  - STUDY DESIGN: Observational study to validate a scale. OBJECTIVE: To translate,
      culturally adapt, and validate the Oswestry Disability Index (ODI), version 2.1a.
      SUMMARY OF BACKGROUND DATA: The ODI is one of the most frequently used tools to
      evaluate disability in patients with low back pain. Its psychometric properties
      have shown to be highly reliable. Currently, no validated Colombian version is
      available. METHODS: The ODI (2.1a) was translated into Spanish and this
      translated version was analyzed in terms of semantic and linguistic equivalence.
      Then, the Spanish version was translated back into English. The first time, the
      ODI was administered to a total of 111 patients with back pain. Internal
      consistency, construct validity, content validity and criterion validity were
      evaluated for the scale. The inter-rater reliability was evaluated by 2 different
      observers a day apart from each other and the intra-rater reliability was
      determined by the same observer, 7 days apart. A sensitivity-to-change analysis
      was performed on 81 patients. RESULTS: Of the sample, 67.6% were women, with a
      mean (SD) age of 44.88 (16.38) years. Cronbach alpha coefficient was 0.86. Inter
      rater reliability yielded an intraclass correlation coefficient (ICC) of 0.94
      whereas intrarater reliability yielded an ICC of 0.95. Pearson correlation
      between ODI and each of the 8 domains of SF-36, was statistically significant.
      Construct validity, when comparing extremely acute and chronic groups, did not
      show any differences (P = 0.409). Concurrent criterion validity between ODI and
      Roland-Morris Disability Questionnaire (RMQ) was r = 0.75; between ODI and the
      Visual Analog Scale (VAS) was r = 0.540. For patients who received an
      intervention, the value of this change was 1.2. CONCLUSION: ODI-C is a helpful,
      reliable and valid tool in Colombia for back pain patient follow-up and
      assessment, regardless the stage of the evolution. It is an observational study
      to validate the Oswestry disability index (ODI) in the Spanish language. ODI is
      the most used tool in evaluating disability related to low back pain. The
      psychometric properties were evaluated in Colombia and the results were very
      good, similar to other studies.

PMID- 22138785
TI  - Nightmare of lumbar diskectomy: aorta laceration.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To present a rare case of a patient who
      during posterior lumbar spinal decompression and diskectomy underwent a
      laceration of the aorta. The patient survived with prompt treatment. SUMMARY OF
      BACKGROUND DATA: Intraoperative injuries of the prevertebral and pelvic vessels
      are infrequent but serious complications of posterior lumbar disc surgery. Injury
      may cause laceration of the vessel with acute life-threatening retroperitoneal
      hemorrhage, which is usually massive. The aortic bifurcation is closely
      approximated to the anterior surface of the L4-L5 disc. METHODS: A 70-year-old
      gentleman with prolapsed intervertebral disc between fourth and fifth lumbar
      vertebrae and left-sided radiculopathy of L5 root was operated with L4-L5
      laminectomy and L4-L5 diskectomy. During diskectomy, it was noticed by the
      surgeon that there was one episode of giving way of the pituitary rongeur
      anteriorly. However, no major bleeding was encountered from the disc space
      immediately after the event; vital signs were stable hemodynamically and we
      completed the diskectomy. Five minutes later, we noted the dural sac to have a
      collapsing pulsation. Prevertebral vessel injury was suspected. Patient became
      pulseless. RESULTS: We turned the patient supine for cardiopulmonary
      resuscitation without extubation. Vascular surgeons proceeded with laparotomy.
      Huge retroperitoneal hematoma and a 1.5 * 1.5 cm laceration at the bifurcation of
      aorta were noted anterior to the L4-L5 intervertebral disc. The vascular surgeon
      repaired the aorta by primary repair. The patient was extubated on day 5 and was
      allowed to ambulate. He was discharged subsequently with a normal neurological
      and vascular examination. No pseudoaneurysm or arteriovenous fistula formation
      was detected on magnetic resonance imaging and magnetic resonance angiography at
      2 years follow-up. CONCLUSION: Iatrogenic vascular injury during posterior lumbar
      disc surgery, although rare, should be suspected if signs of circulatory
      instability or abnormal pulsation of the dural sac are noted, especially if any
      lapse in the ordinary technique has been observed. In preoperative imaging, note
      the position of the aorta and prevertebral veins and the depth and integrity of
      the anterior wall of the disc.

PMID- 22138787
TI  - Assignment strategies for aliphatic protons in the solid-state in randomly
      protonated proteins.
AB  - Biological solid-state nuclear magnetic resonance spectroscopy developed rapidly
      in the past two decades and emerged as an important tool for structural biology.
      Resonance assignment is an essential prerequisite for structure determination and
      the characterization of motional properties of a molecule. Experiments, which
      rely on carbon or nitrogen detection, suffer, however, from low sensitivity.
      Recently, we introduced the RAP (Reduced Adjoining Protonation) labeling scheme,
      which allows to detect backbone and sidechain protons with high sensitivity and
      resolution. We present here a (1)H-detected 3D (H)CCH experiment for assignment
      of backbone and sidechain proton resonances. Resolution is significantly improved
      by employing simultaneous (13)CO and (13)Cbeta J-decoupling during evolution of
      the (13)Calpha chemical shift. In total, ~90% of the (1)Halpha-(13)Calpha
      backbone resonances of chicken alpha-spectrin SH3 could be assigned.

PMID- 22138788
TI  - High electrochemical activity of the oxide phase in model ceria-Pt and ceria-Ni
      composite anodes.
AB  - Fuel cells, and in particular solid-oxide fuel cells (SOFCs), enable high
      efficiency conversion of chemical fuels into useful electrical energy and, as
      such, are expected to play a major role in a sustainable-energy future. A key
      step in the fuel-cell energy-conversion process is the electro-oxidation of the
      fuel at the anode. There has been increasing evidence in recent years that the
      presence of CeO(2)-based oxides (ceria) in the anodes of SOFCs with oxygen-ion
      conducting electrolytes significantly lowers the activation overpotential for
      hydrogen oxidation. Most of these studies, however, employ porous, composite
      electrode structures with ill-defined geometry and uncontrolled interfacial
      properties. Accordingly, the means by which electrocatalysis is enhanced has
      remained unclear. Here we demonstrate unambiguously, through the use of ceria
      metal structures with well-defined geometries and interfaces, that the near
      equilibrium H(2) oxidation reaction pathway is dominated by electrocatalysis at
      the oxide/gas interface with minimal contributions from the oxide/metal/gas
      triple-phase boundaries, even for structures with reaction-site densities
      approaching those of commercial SOFCs. This insight points towards ceria
      nanostructuring as a route to enhanced activity, rather than the traditional
      paradigm of metal-catalyst nanostructuring.

PMID- 22138789
TI  - Biodegradable poly(amine-co-ester) terpolymers for targeted gene delivery.
AB  - Many synthetic polycationic vectors for non-viral gene delivery show high
      efficiency in vitro, but their usually excessive charge density makes them toxic
      for in vivo applications. Here we describe the synthesis of a series of high
      molecular weight terpolymers with low charge density, and show that they exhibit
      efficient gene delivery, some surpassing the efficiency of the commercial
      transfection reagents Polyethylenimine and Lipofectamine 2000. The terpolymers
      were synthesized via enzyme-catalyzed copolymerization of lactone with dialkyl
      diester and amino diol, and their hydrophobicity adjusted by varying the lactone
      content and by selecting a lactone comonomer of specific ring size. Targeted
      delivery of the pro-apoptotic TRAIL gene to tumour xenografts by one of the
      terpolymers results in significant inhibition of tumour growth, with minimal
      toxicity both in vitro and in vivo. Our findings suggest that the gene delivery
      ability of the terpolymers stems from their high molecular weight and increased
      hydrophobicity, which compensates for their low charge density.

PMID- 22138790
TI  - Morphological instability leading to formation of porous anodic oxide films.
AB  - Electrochemical oxidation of metals, in solutions where the oxide is somewhat
      soluble, produces anodic oxides with highly regular arrangements of pores.
      Although porous aluminium and titanium oxides have found extensive use in
      functional nanostructures, pore initiation and self-ordering are not yet
      understood. Here we present an analysis that examines the roles of oxide
      dissolution and ionic conduction in the morphological stability of anodic films.
      We show that patterns of pores with a minimum spacing are possible only within a
      narrow range of the oxide formation efficiency (the fraction of oxidized metal
      atoms retained in the film), which should exist when the metal ion charge exceeds
      two. Experimentally measured efficiencies, over diverse anodizing conditions on
      both aluminium and titanium, lie within the different ranges predicted for each
      metal. On the basis of these results, the relationship between dissolution
      chemistry and the conditions for pore initiation can now be understood in
      quantitative terms.

PMID- 22138791
TI  - Electron spin coherence exceeding seconds in high-purity silicon.
AB  - Silicon is one of the most promising semiconductor materials for spin-based
      information processing devices. Its advanced fabrication technology facilitates
      the transition from individual devices to large-scale processors, and the
      availability of a (28)Si form with no magnetic nuclei overcomes a primary source
      of spin decoherence in many other materials. Nevertheless, the coherence
      lifetimes of electron spins in the solid state have typically remained several
      orders of magnitude lower than that achieved in isolated high-vacuum systems such
      as trapped ions. Here we examine electron spin coherence of donors in pure (28)Si
      material (residual (29)Si concentration <50 ppm) with donor densities of 10(14)
      10(15) cm(-3). We elucidate three mechanisms for spin decoherence, active at
      different temperatures, and extract a coherence lifetime T(2) up to 2 s. In this
      regime, we find the electron spin is sensitive to interactions with other donor
      electron spins separated by ~200 nm. A magnetic field gradient suppresses such
      interactions, producing an extrapolated electron spin T(2) of 10 s at 1.8 K.
      These coherence lifetimes are without peer in the solid state and comparable to
      high-vacuum qubits, making electron spins of donors in silicon ideal components
      of quantum computers, or quantum memories for systems such as superconducting
      qubits.

PMID- 22138792
TI  - Physical ageing of the contact line on colloidal particles at liquid interfaces.
AB  - Young's law predicts that a colloidal sphere in equilibrium with a liquid
      interface will straddle the two fluids, its height above the interface defined by
      an equilibrium contact angle. This has been used to explain why colloids often
      bind to liquid interfaces, and has been exploited in emulsification, water
      purification, mineral recovery, encapsulation and the making of nanostructured
      materials. However, little is known about the dynamics of binding. Here we show
      that the adsorption of polystyrene microspheres to a water/oil interface is
      characterized by a sudden breach and an unexpectedly slow relaxation. The
      relaxation appears logarithmic in time, indicating that complete equilibration
      may take months. Surprisingly, viscous dissipation appears to play little role.
      Instead, the observed dynamics, which bear strong resemblance to ageing in glassy
      systems, agree well with a model describing activated hopping of the contact line
      over nanoscale surface heterogeneities. These results may provide clues to
      longstanding questions on colloidal interactions at an interface.

PMID- 22138793
TI  - Second-harmonic generation in silicon waveguides strained by silicon nitride.
AB  - Silicon photonics meets the electronics requirement of increased speed and
      bandwidth with on-chip optical networks. All-optical data management requires
      nonlinear silicon photonics. In silicon only third-order optical nonlinearities
      are present owing to its crystalline inversion symmetry. Introducing a second
      order nonlinearity into silicon photonics by proper material engineering would be
      highly desirable. It would enable devices for wideband wavelength conversion
      operating at relatively low optical powers. Here we show that a sizeable second
      order nonlinearity at optical wavelengths is induced in a silicon waveguide by
      using a stressing silicon nitride overlayer. We carried out second-harmonic
      generation experiments and first-principle calculations, which both yield large
      values of strain-induced bulk second-order nonlinear susceptibility, up to 40 pm
      V(-1) at 2,300 nm. We envisage that nonlinear strained silicon could provide a
      competing platform for a new class of integrated light sources spanning the near-
      to mid-infrared spectrum from 1.2 to 10 MUm.

PMID- 22138794
TI  - Is the fasting calcium/creatinine a bone resorption marker in patients with
      calcium renal stones?
AB  - Osteoporosis and osteopenia are an important endocrine-metabolic disease that
      affect women and men from a certain age and it has a high risk and health cost.
      The aim of this short communication is to show that fasting calcium/creatinine
      ratio in patients with calcium stones is a marker of bone resorption.We studied
      180 patients with renal stones with calcium composition and the relationship of
      them between the calcium/creatinine in urine after 8 h of fasting with bone
      densitometry (T-score) and values of bone resorption marker beta-crosslaps
      (ng/ml). The Pearson correlation test was applied for the analysis of linear
      correlations between quantitative variables.We have observed a statistically
      significant positive linear correlation between the fasting calcium/creatinine
      and serum and beta-crosslaps (R = 0.534, p < 0.0001) and a statistically
      significant negative linear correlation between fasting calcium/creatinine and T
      score of bone densitometry in hip (R = -0.237, p = 0.002), femoral neck (R = 
      0.217, p = 0.009) and lumbar spine (R = 0.292, p = 0.001).The fasting ratio
      calcium/creatinine in urine is associated with increased levels of beta-crosslaps
      marker and therefore may be useful as a marker of bone resorption in these
      patients.

PMID- 22138795
TI  - Ultrafast recombination for NiO sensitized with a series of perylene imide
      sensitizers exhibiting Marcus normal behaviour.
AB  - Ultrafast recombination observed from several perylene imide sensitizers bound to
      NiO appears to align with Marcus normal region behaviour; this indicates
      recombination to intra-bandgap states.

PMID- 22138796
TI  - Real-life effect of classical homeopathy in the treatment of allergies: A
      multicenter prospective observational study.
AB  - OBJECTIVE: The prevalence of allergic disorders in western industrialized
      countries has steadily increased during the last three decades. Public acceptance
      of complementary treatment methods is high. The aim of this study was to assess
      the real-life efficacy of classical homeopathic treatment and the potential to
      reduce conventional medication dosage. METHODS: A prospective multicenter
      observational study was conducted by general practitioners specializing in
      homeopathy in nine Austrian test centers. Personal data and symptoms of allergic
      patients diagnosed with allergic conjunctivitis, allergic rhinitis, bronchial
      asthma and neurodermatitis before and after homeopathic treatment were assessed
      by means of questionnaires (classification of patients' condition by using visual
      analogue scales/VAS). RESULTS: 40 out of 44 patients originally recruited for the
      trial were found to meet the eligibility criteria. All clinical symptoms were
      shown to improve substantially, in most cases quite markedly (p < 0.001). 21
      patients undergoing conventional medication therapy at baseline (62%) were able
      to discontinue at least one medication, while the remaining patients (38%)
      reported a dose reduction in at least one medication. No side effects were
      reported during treatment. CONCLUSION: The symptoms of patients undergoing
      homeopathic treatment were shown to improve substantially and conventional
      medication dosage could be substantially reduced. While the real-life effect
      assessed indicates that there is a potential for enhancing therapeutic measures
      and reducing healthcare cost, it does not allow to draw conclusions as to the
      efficacy of homeopathic treatment per se.

PMID- 22138797
TI  - [Validity of the use of L-Tyrosine to enhance fertility of female domestic
      animals. A study on the evidence from the literature].
AB  - OBJECTIVE: In order to improve fertility in female domestic animals, especially
      in bitches, several authors recommend the feeding of the amino acid L-Tyrosine
      during the follicular phase of the oestrous cycle. The aim of this article was a
      systematic and statistical analysis of current literature in terms of evidence
      based medicine. MATERIALS AND METHODS: Literature research, statistical analysis
      and classification in levels of evidence. RESULTS: Fifteen German and two English
      studies on the effect of L-Tyrosine on the fertility in domestic animals were
      found. The statistical analysis and evaluation of evidence showed that most
      studies feature methodical deficits and often findings were inconsistent with one
      another. CONCLUSION AND CLINICAL RELEVANCE: Heterogeneous results indicate a
      considerable need for further research on the effectiveness and dose of L
      Tyrosine to legitimate its appliance in practice.

PMID- 22138798
TI  - [Influence of an infusion of 5- or 20% glucose solution on blood glucose and
      inorganic phosphate concentrations in dairy cows].
AB  - OBJECTIVE: The study was performed to evaluate the influence of an intravenous
      infusion of 5% and 20% dextrose solution on the plasma concentration of glucose
      and inorganic phosphate in healthy, dairy cows. MATERIAL AND METHODS: Ten
      healthy, lactating, nonpregnant 3 to 6 year-old Holstein-Friesian cows were
      included in this investigation. The daily milk yield was 20.3+/-2.7 liters. Blood
      plasma concentrations of inorganic phosphate and glucose were determined before,
      during, immediately and 60 minutes after infusion of 0.9% physiological saline,
      5% or 20% dextrose solution. RESULTS: A statistically significant influence of
      dextrose infusion on blood glucose concentration was observed. After 20% dextrose
      infusion (200 g dextrose) the blood glucose concentration increased by
      approximately 13.26 mmol/l. The administration of 5% dextrose solution (50 g
      dextrose) yielded an increase of blood glucose concentration by 3.31 mmol/l.
      There was no significant correlation between plasma inorganic phosphate
      concentrations and infusion of 0.9% saline, 5% or 20% dextrose solution.
      CONCLUSION AND CLINICAL RELEVANCE: Intravenous administration of 1000 ml of 5% or
      20% dextrose solution does not induce a lasting plasma phosphate reduction and is
      suitable for elevating the blood glucose concentration.

PMID- 22138799
TI  - [Analysis of feedstuff for pigs, sent in from veterinary practices for quality
      control].
AB  - OBJECTIVE: Nutritional disorders and a reduced performance are common reasons to
      send in feedstuffs for quality control. The following review illustrates the main
      nutritional-related problems on pig farms and presents possible causal
      relationships between feed/feeding and health disorders. MATERIAL AND METHODS:
      The analysis results of feedstuff and drinking water samples that were sent to
      the institute for animal nutrition between 2000 and 2009 were evaluated
      retrospectively. RESULTS: Certain trends were revealed. Whereas previously
      fertility disorders gave rise to analysis of food samples, in recent years the
      grinding intensity of mixed feeds (potential relationship to gastric ulcers) has
      become of more interest. Mixed feed in meal form (n=143) showed a usual particle
      size structure, whereas pelleted and crumbled diets exhibited undesirable, higher
      proportions of fine particles. A contamination with pests was only found in a few
      feed samples (0.9% of analysed feedstuffs in 2007). With only a few exceptions
      the feedstuffs were of a satisfactory hygienic quality. With respect to the
      chemical composition of the mixed feeds, differences between analysed and
      labelled levels were detected in terms of crude fibre (63.0% of 138 analysed feed
      samples). More than 50% of the feedstuffs (n=64) showed aberrations in the
      botanical composition. Samples of drinking water were checked to an increasing
      extent (n=120 in 2009) probably due to the fact that drinking water is defined by
      law as a feedstuff and evaluation criteria exist. Elevated levels of iron and
      aerobe bacteria (in 50% and 30.8% of samples, respectively) were among the most
      common findings. CONCLUSION AND CLINICAL RELEVANCE: The spectrum of analyses has
      been expanded in recent years. In many cases a relationship could be found
      between clinical symptoms and alterations within the feed or the drinking water.

PMID- 22138800
TI  - [Infectious agent detection in reproductive disorders in swine herds.
      Retrospective evaluation of diagnostic laboratory examinations].
AB  - OBJECTIVE: The detection rate of various viral and bacterial agents causing
      reproductive failure in sows was analysed. MATERIAL AND METHODS: Samples from
      abortion/uterus (n=714), sera from weak born piglets (n=317), cervical swabs
      (n=881) and urogenital organs from slaughtered sows (n=416) that had been
      submitted between January 2006 and June 2009 were included in this analysis.
      Various PCR assays were run to detect PRRSV, PCV2, PPV, Chlamydia spp. and
      Leptospira spp. Other bacterial agents were examined using standard cultural
      methods. RESULTS: In material from abortion, detection rates of 14.7% for PCV2
      and 6.8% for PRRSV EU genotype were revealed using PCR screening. The other
      agents were detected in single cases only (PPV 2.2%, PRRSV US genotype 1.8%,
      Chlamydia spp. 1.0%, Leptospira spp. 0.8%). Single PCR yielded a significantly
      higher detection rate for PCV2 than PCR screening. Comparing results from
      abortion/uterus and serum samples from weak born piglets, a significantly higher
      detection rate of PCV2 and PRRSV was found in sera. Bacteriological examination
      revealed bacterial agents in more than 75% of all cervical swabs. However, half
      of them had to be considered as contaminated due to the diversity of the isolated
      bacteria. Bacteriological testing of urogenital organs from slaughtered sows
      yielded positive results in 60% of all samples, with a remarkably lower
      proportion of contaminated samples of 7.4%. CONCLUSION: It is assumed that 60-70%
      of all cases of reproductive failure are similarly not caused by primary
      infections. If PRRSV infection is suspected, examination of serum samples from
      weak born piglets is much better than the testing of foetuses or other material
      from abortion. Due to poor detection rates, the examination of foetuses/abortion
      material by screening PCR cannot be recommended. In the case of bacterial
      infections of the urogenital system, the cultural examination of organs from
      slaughtered sows is more often successful than the testing of cervical swabs.

PMID- 22138801
TI  - [Growth of the hoof horn in horses with chronic laminitis].
AB  - Objective of the study was to investigate whether a correlation between rotation
      and/or sinking of the third phalanx (P3) and changes of horn growth on the hoof
      wall exists. MATERIAL AND METHODS: In 117 hooves of euthanatized or slaughtered
      horses with chronic laminitis the rotating angle to palmar/plantar and
      medial/lateral and a sinking of P3 were assessed on radiographs. Defined
      distances were measured on the dorsal hoof wall as well as in the heel to assess
      the horn growth of a hoof. On the basis of saw cuts of the hooves, the course of
      the horn tubes was judged. RESULTS: A rotation angle of approximately 8 degrees 
      was found to predict a change in the direction of the growth of the hoof horn at
      the dorsal and the lateral hoof wall. In addition, a correlation between the
      rotation angle of P3 and the length of growth of the hoof could be highlighted. A
      greater angle could lead to a larger interruption of the dorsal horn growth;
      meanwhile the palmar/plantar horn growth appeared to be independent. A
      correlation between a medial/lateral rotation of the pedal bone and the length of
      the horn was not observed. CONCLUSION: The direction change of the horn tubes
      might cause a decrease of the visible length growth of a chronic laminitic hoof.
      Therefore, it appears to be important to differentiate between the externally
      visible length of the hoof and the real growth of the horn. Apparently, the
      amount of horn produced is the same on the dorsal hoof wall and in the heel. In
      horses with moderate laminitis the horn tubes on the dorsal wall were lying in
      folds, with the consequence of a decreased visible length growth. Only the
      formation of wrinkles of the horn tubes on the dorsal hoof wall reduced the
      visible wall length. Formation of wrinkles of the horn tubes in the heel could
      not be observed. Interestingly, the results of this study show that the lateral
      rotation of P3 does not promote the formation of wrinkles of the horn tubes along
      the lateral or medial hoof wall. CLINICAL RELEVANCE: According to our results, a
      resection of the dorsal hoof wall might be a sensible therapeutic approach in
      horses with chronic laminitis showing a rotation of P3 of at least 8 degrees .

PMID- 22138802
TI  - Comparison of three methods of sampling for endometrial cytology in the mare.
      Preliminary study.
AB  - OBJECTIVE: This prospective study aims to compare three different sampling
      techniques for the collection of endometrial cytological specimens in the mare:
      the guarded culture swab, the uterine cytobrush and the low volume uterine flush.
      MATERIAL AND METHODS: The study population consisted of six healthy Standardbred
      mares in dioestrus. In each mare an acute endometritis was induced by performing
      a low- volume uterine flush 6days after ovulation using a sterile isotonic
      solution (lactated Ringer's solution or ViGroTM Complete Flush Solution). Two
      days after initiating inflammation, samples were collected from each mare using
      the three compared techniques: the double guarded cotton swab, the uterine
      cytobrush and the low volume uterine flush. The cytological evaluation of the
      samples was based on following criteria: the quality and cellularity of the
      samples and the number of neutrophils recovered. RESULTS: The uterine cytobrush
      yielded slides of significantly (p=0.02) better quality than the low volume
      uterine flush. There was no significant difference between the cytobrush and the
      double guarded swab technique for the quality. There was no difference between
      techniques in the number of endometrial cells (p=0.55) and neutrophils recovered
      (p=0.28). CONCLUSION AND CLINICAL RELEVANCE: Endometrial cytology is a practical
      method for the diagnosis of acute endometrial inflammation in the mare. Since no
      difference in the number of neutrophils was found between the three techniques,
      the choice of the sampling method should be based on other factors such as
      practicability, costs and disadvantages of each technique.

PMID- 22138803
TI  - Tail amputation for treatment of osteomyelitis of the first and second coccygeal
      vertebrae in a cow.

PMID- 22138804
TI  - [Control of bovine fasciolosis].

PMID- 22138805
TI  - The role of prophylactic antimicrobials during autologous stem cell
      transplantation: a single-center experience.
AB  - The aim of this study was to investigate the efficacy of antibiotic prophylaxis
      in patients undergoing autologous stem cell transplantation (ASCT) for multiple
      myeloma and non-Hodgkin lymphoma. Among 232 ASCT cases performed at the Asan
      Medical Center, 114 cases underwent treatment with ciprofloxacin, fluconazole,
      and acyclovir (between January 2001 and August 2005), while 118 cases were
      performed without antimicrobial prophylaxis (between February 2004 and June
      2008). The two-rate chi2 test was applied to accommodate the differences in
      neutropenia duration. The incidence of febrile episodes was 9.8 cases per 100
      person-days in the prophylactic group, while it was 16.2 cases in the no
      prophylactic group (p<0.001). The rate of unexplained fever was 8.0 cases per 100
      person-days in the prophylactic group, while it was 13.8 cases in the no
      prophylactic group (p<0.001). The rate of clinically and microbiologically
      documented infection was 1.7 cases per 100 person-days in the prophylactic group,
      while it was 2.3 cases in the no-prophylactic group (p=0.404). There were fewer
      cases of methicillin-susceptible Staphylococcus aureus infection and a greater
      number of quinolone-resistant Escherichia coli in the prophylactic group compared
      with the no-prophylactic group (p=0.056 and p=0.040, respectively). The
      prophylactic antimicrobials reduced the incidence rate of febrile episodes,
      especially unexplained fever, despite there being no difference in the incidence
      of documented infection. Resistant microbe infection occurred more frequently in
      the prophylactic group.

PMID- 22138806
TI  - Return to work after burn injury:  a systematic review.
AB  - Consequences of major burn injuries often include losing the ability to engage in
      basic life functions such as work or employment. As this is a developing area of
      importance in burn care, the goal of this study was to perform a systematic
      review of the burn literature to ascertain a comprehensive view of the literature
      and identify return to work (RTW) factors where possible. A search was conducted
      and peer-reviewed studies that investigated predictors and barriers of returning
      to work of those with burn injuries, published since 1970 and written in English,
      were examined. From the 216 articles initially identified in the search, 26
      studies were determined to meet inclusion criteria. Across studies, the mean age
      was 33.63 years, the mean TBSA was 18.94%, and the average length of stay was 20
      days. After 3.3 years (41 months) postburn, 72.03% of previously employed
      participants had returned to some form of work. Important factors of RTW were
      identified as burn location, burn size, treatment variables, age, pain,
      psychosocial factors, job factors, and barriers. This systematic review suggests
      multiple conclusions. First, there is a significant need for attention to this
      area of study given that nearly 28% of all burn survivors never return to any
      form of employment. Second, the RTW literature is in need of coherent and
      consistent methodological practices, such as a sound system of measurement.
      Finally, this review calls for increased attention to interventions designed to
      assist survivors' ability to function in an employed capacity.

PMID- 22138807
TI  - Epidemiology and impact of scarring after burn injury:  a systematic review of
      the literature.
AB  - The purpose of this study was to perform a systematic review of the existing
      literature on the incidence of hypertrophic scarring and the psychosocial impact
      of burn scars. In a comprehensive literature review, the authors identified 48
      articles published since 1965 and written in English which reported the incidence
      and risk factors for hypertrophic scarring or assessed outcomes related to
      scarring. Most studies had important methodological limitations limiting the
      generalizability of the findings. In particular, the absence of standardized
      valid measures of scarring and other outcome variables was a major barrier to
      drawing strong conclusions. Among studies on hypertrophic scarring, the
      prevalence rate varied between 32 and 72%. Identified risk factors included dark
      skin, female gender, young age, burn site on neck and upper limb, multiple
      surgical procedures, meshed skin graph, time to healing, and burn severity. With
      regard to psychosocial outcomes, two studies compared pediatric burn survivors
      with a nonburn comparison group on a body image measure; neither study found
      differences between groups. Across studies, burn severity and location had a
      modest relationship with psychosocial outcome variables. Psychosocial variables
      such as social comfort and perceived stigmatization were more highly associated
      with body image than burn characteristics. To advance our knowledge of the
      epidemiology of scars and the burden of scars, future studies need to implement
      more rigorous methodologies. In particular, standardized valid measures of
      scarring and other outcomes should be developed. This process could be
      facilitated by an international collaboration among burn centers.

PMID- 22138808
TI  - Necrotizing peripheral vasculitis/vasculopathy following the use of cocaine laced
      with levamisole.
AB  - The objective of this study was to describe a novel presentation of peripheral
      vasculitis associated with levamisole-adulterated cocaine. Cocaine abuse is
      widespread in the United States with 5.3 million people using cocaine in 2008.
      Over the past decade, drug enforcement officials have noticed the presence of
      levamisole in confiscated cocaine samples as an adulterant. Known side effects of
      cocaine-related levamisole ingestion have included agranulocytosis and a
      cutaneous acral purpura that is histopathologically characterized by a mixture of
      inflammation (vasculitis) and occlusion (vasculopathy). A 54-year-old man who
      nasally ingested cocaine laced with levamisole developed widespread
      necrotic/purpuric skin lesions on approximately 20% of his body with an acral
      accentuation. These lesions were complicated by multiple areas of sloughing and
      necrosis. He was initially treated with topical silver sulfadiazine dressing
      changes but progressed to require debridement and split-thickness skin grafting.
      Peripheral vasculitis/vasculopathy with severe necrosis resembling Coumadin
      necrosis is a relatively recently recognized sequelae from levamisole-adulterated
      cocaine use.

PMID- 22138809
TI  - Necrotizing fasciitis:  a six-year experience.
AB  - Necrotizing fasciitis (NF) is a life-threatening infectious disease whose
      incidence has been on the rise. Commonly a consequence of group A beta-hemolytic
      Streptococcus infection, it results in high levels of morbidity and mortality.
      Diagnosis is difficult and treatment involves emergent surgical intervention and
      antibiotic therapy. The aim of this study is to examine the incidence of NF in
      Manitoba with the goal of observing whether there is a geographic variation in
      incidence and outcomes based on Regional Health Authorities (RHAs). This is a 6
      year retrospective chart review of all NF patients who presented to the Health
      Sciences Center from 2004 to 2009. A total of 130 patients satisfied the
      inclusion criteria. The mean age was 47 +/- 16 years. The most common
      comorbidities were diabetes (33.8%) and hypertension (33.1%). The overall
      mortality was 13.1% with advanced age being an independent risk factor (P < .05).
      Lower extremity was the most common location of infection (44.6%) and the most
      common causative organism was group A beta-hemolytic Streptococcus (63.9%). The
      type of infection (mono- vs. polymicrobial) was not found to affect length of
      stay, amputation rate, or mortality. There was no statistical difference in rate
      of amputations, length of stay, or mortality based on RHA. Incidence within the
      province, however, varied significantly based on RHA and ethnicity (P < .05). We
      determined that regardless of origin before admission, all our patients have
      equivalent prognosis. Burntwood RHA was found to have substantially higher
      incidence than the rest of the province, and higher incidence was established
      among the Aboriginal population.

PMID- 22138810
TI  - Silicone action in the open wound:  a hypothesis.

PMID- 22138811
TI  - When a hero becomes a patient: firefighter burn injuries in the National Burn
      Repository.
AB  - Firefighters receive significant training and are outfitted with state-of-the-art
      protective equipment. However, given the unpredictable nature of their work
      environment, injuries still occur. The National Burn Repository (NBR) was viewed
      as a resource for defining the epidemiology of these injuries on a national level
      and to identify predictive factors for outcomes in this population. The NBR was
      queried for the occupation of "firefighter" for the years 1990-2008. Records were
      screened for completeness, and 597 patients were identified for analysis. Data
      examined included demographics, %TBSA burn, length of stay (LOS), injury
      circumstance, and disposition. Multiple linear regression models were created to
      determine factors related to outcome measures. The majority of patients were
      white (84%) and male (96%). The mean age was 35 years. Most injuries were caused
      by fire/flame (73%). Only six deaths (1%) were reported. Most injuries were work
      related (86%), and most patients were discharged home (92%). Inhalation injury
      was documented in 9% of patients. The mean LOS was 6.5 +/- 11.3 days (median 2
      days), and few patients had critical care requirements. The average %TBSA was 6
      +/- 11.7%. Patients with larger injuries had increased LOS. The presence of
      inhalation injury, elevated carboxyhemoglobin levels, and advancing age were
      significantly associated with larger burns. From the NBR data, most firefighter
      burn injuries were small, and few firefighter burn patients required critical
      care resources or had significant disability. Firefighters comprise a small
      number of burn center admissions each year, yet they are an important population
      to consider for burn prevention efforts.

PMID- 22138812
TI  - Oral hypertonic electrolyte-glucose/mosapride complex solution for resuscitation
      of burn shock in dogs.
AB  - The objective of this study is to investigate the effect of oral feeding of an
      electrolyte glucose mosapride solution for resuscitation in dogs with shock after
      a 35% TBSA full-thickness burn and the effect of mosapride on gastric emptying
      time. Eighteen male Beagle dogs were randomly divided into intravenous isotonic
      solution group, intragastric hypertonic solution group, and mosapride group after
      they were subjected to a 35% TBSA full-thickness flame injury. In intravenous
      isotonic solution group (I group), isotonic electrolyte glucose solution was
      given through vein with adoption of the Parkland formula. The resuscitation fluid
      in intragastric hypertonic solution group (H group) and mosapride group (M group)
      consisted of 1.8% NaCl and 5% glucose, the total fluid volume was one half of
      that for I group, and it was given in divided amount every 2 hours. Mosapride was
      added to the resuscitation fluid in mosapride group. Fluid replacement was begun
      30 minutes after the injury in all the groups. Mean arterial pressure (MAP),
      cardiac output index (CI), intrathoracic blood volume index (ITBI), blood volume
      (BV), serum sodium concentration, intestinal mucosal blood flow (IMBF), gastric
      emptying, and serum motilin levels were determined at different time points. The
      urinary output of all animals was measured immediately after burn upto 360
      minutes postburn. CI, ITBI, BV, and IMBF were all decreased obviously after burn.
      In I group and M group, CI, ITBI, BV, and IMBF were increased gradually after
      resuscitation, and they were significantly higher than that of H group (P < .05).
      MAP in all three groups was lowered significantly and then gradually recovered,
      showing no significant difference among groups. The urinary output in M group was
      similar to that in I group (P > .05), and it was higher than that in H group (P <
      .05). Serum sodium level in H group and M group increased in varying degrees and
      were markedly higher compared with the I group (P < .05). Postburn gastric
      emptying in H group was much more delayed (P < .05), but in M group it was much
      faster. Motilin level in the latter group also increased gradually postburn and
      was markedly higher than that of the other two groups (P < .05). At the early
      stage of 35% TBSA third-degree burns, gavage of 1.8% hypertonic electrolytes
      glucose ends in slow gastric emptying, resulting in delayed recovery from shock.
      When a prokinetic drug mosapride was added to the solution, gastric emptying
      could be accelerated and a resuscitation effect similar to that of intravenous
      isotonic fluid resuscitation can be achieved, while total fluid volume can be
      decreased by half.

PMID- 22138813
TI  - Gliosis in the mouse hippocampus without neuronal death after systemic
      administration of high dosage of tetanus toxin.
AB  - Tetanus toxin (TeT), an exotoxin, has been studied to cause tetanus in mammalian
      brains, and it can block the release of some neurotransmitters and affect seizure
      propagation. In the present study, we investigated neuronal damage/death and
      glial changes in the mouse hippocampus after systemic administration
      (intraperitoneal injection) of TeT 10 and 100 ng/kg. In both the 10 and 100 ng/kg
      TeT-treated groups, no neuronal death occurred in any subregions of the mouse
      hippocampus until 24 h post-treatment; however, there were changes in glia in the
      hippocampus depending on time course and dosage. The morphology of GFAP
      immunoreactive astrocytes and Iba-1-immunoreactive microglia was apparently
      changed in the 100 ng/kg TeT treated-group compared to the 10 ng/kg TeT treated
      group. In the 100 ng/kg TeT treated-group, they were increased in size and their
      immunoreactivity was distinctively increased from 12 h post-treatment. We also
      found that their protein levels were increased in the hippocampus at 12 h post
      treatment of 100 ng/kg TeT. In conclusion, these results indicate that the
      systemic administration of 100 ng/kg TeT induced a distinctive microglia changes
      in the mouse hippocampus without any neuronal death/damage.

PMID- 22138814
TI  - The phenotypic distribution of quantitative traits in a wild mouse F1 population.
AB  - The human complex diseases such as hypertension, precocious puberty, and diabetes
      have their own diagnostic thresholds, which are usually estimated from the
      epidemiological data of nature populations. In the mouse models, numerous
      phenotypic data of complex traits have been accumulated; however, knowledge of
      the phenotypic distribution of the natural mouse populations remains quite
      limited. In order to investigate the distribution of quantitative traits of wild
      mice, 170 F1 progeny aged 8-10 weeks and derived from wild mice collected from
      eight spots in the suburbs of Shanghai were tested for their values of anatomic,
      blood chemical, and blood hematological parameters. All the wild mice breeders
      were of Mus. m. musculus and Mus. m. castaneus maternal origin according to the
      single nucleotide polymorphism (SNP) markers of the mitochondrial DNA. The
      results showed that phenotypes in wild mice had a normal distribution with four
      to six times the standard deviation. For the majority of the traits, the wild
      outbred mice and laboratory inbred mice have significantly different ranges and
      mean values, whereas the wild mice did not necessarily show more phenotypic
      diversity than the inbred ones. Our data also showed that natural populations may
      have some unique phenotypes related to sugar and protein metabolism, as the mean
      value of wild mice differ dramatically from the inbred mice in the levels of
      blood glucose, BUN (blood urea nitrogen), and total blood protein. The
      epidemiological information of the complex traits in the nature population from
      our study provided valuable reference for the application of mouse models in
      those complex disease studies.

PMID- 22138815
TI  - Magnetic resonance imaging flow quantification of non-occlusive excimer laser
      assisted EC-IC high-flow bypass in the treatment of complex intracranial
      aneurysms.
AB  - The patency of a bypass plays an important role in the postoperative recovery of
      patients especially when dealing with complicated intracranial aneurysms. In this
      study two-dimensional phase contrast magnetic resonance angiography (PC-MRA) was
      used to measure cerebral blood flow in 23 patients before extracranial
      intracranial high-flow bypass surgery using the excimer laser-assisted non
      occlusive anastomosis (ELANA) technique and in 15 patients following surgery. The
      results showed that PC-MRA is a suitable technique for assessing bypass patency
      and that with the ELANA technique the bypass has the capability of compensating
      the blood flow of an occluded internal carotid artery (ACI) in cases of complex
      aneurysms.

PMID- 22138816
TI  - Chiral biointerface materials.
AB  - Chiral phenomena are ubiquitous in nature from macroscopic to microscopic,
      including the high chirality preference of small biomolecules, special steric
      conformations of biomacromolecules induced by it, as well as chirality-triggered
      biological and physiological processes. The introduction of chirality into the
      study of interface interactions between materials and biological systems leads to
      the generation of chiral biointerface materials, which provides a new platform
      for understanding the chiral phenomena in biological system, as well as the
      development of novel biomaterials and devices. This critical review gives a brief
      introduction to the recent advances in this field. We start from the fabrication
      of chiral biointerface materials, and further investigate the stereo-selective
      interaction between biological systems and chiral interface materials to find out
      key factors governing the performance of such materials in given conditions, then
      introduce some special functionalities and potential applications of chiral
      biointerface materials, and finally present our own thinking about the future
      development of this area (108 references).

PMID- 22138817
TI  - Genetic polymorphisms and bronchiolitis obliterans syndrome after lung
      transplantation:  promising results and recommendations for the future.
AB  - Survival rates after lung transplantation are the lowest among solid organ
      transplantations. Long-term survival is limited by the development of chronic
      rejection, known as bronchiolitis obliterans syndrome (BOS). Risk factors, such
      as acute rejection and cytomegalovirus infection, contribute to the development
      of BOS. However, these risk factors alone do not explain the interindividual
      variability seen in the development of BOS. There is growing evidence that
      genetic variations might contribute to an individual's susceptibility to
      rejection. In this systematic review, based on a literature search through
      Medline and Embase, an overview is given of the genetic polymorphisms that have
      been investigated in lung transplant recipients in relation to the devlopment of
      BOS. Functional genetic polymorphisms in the genes of IFNG (+874 A/T), TGFB1
      (+915 G/C), and IL6 (-174 G/C) have been found to be associated with the
      development of BOS and allograft fibrosis after lung transplantation. However,
      confirmation was not consistent across all studied cohorts. Genetic polymorphisms
      in the genes of several Toll-like receptors, mannose-binding lectin, CD14, killer
      immunoglobulin-like receptors, and matrix metalloproteinase-7 were also found to
      be associated with the development of BOS, but these studies need to be
      replicated in independent cohorts. This review shows that there may be
      involvement of genetic polymorphisms in the development of BOS. Genetic risk
      profiling of lung transplant recipients could be a promising approach for the
      future, enabling individualized risk stratification and personalized
      immunosuppressive treatment after transplantation. Further studies are needed to
      define risk alleles.

PMID- 22138818
TI  - Mechanisms of rejection: current perspectives.
AB  - Rejection is the major barrier to successful transplantation. The immune response
      to an allograft is an ongoing dialogue between the innate and adaptive immune
      system that if left unchecked will lead to the rejection of transplanted cells,
      tissues, or organs. Activation of elements of the innate immune system, triggered
      as a consequence of tissue injury sustained during cell isolation or organ
      retrieval and ischemia reperfusion, will initiate and amplify the adaptive
      response. T cells require a minimum of two signals for activation, antigen
      recognition, and costimulation. The activation requirements of naive T cells are
      more stringent than those of memory T cells. Memory T cells are present in the
      majority of transplant recipients as a result of heterologous immunity. The
      majority of B cells require help from T cells to initiate antibody production.
      Antibodies reactive to donor human leukocyte antigen molecules, minor
      histocompatibility antigens, endothelial cells, RBCs, or autoantigens can trigger
      or contribute to rejection early and late after transplantation. Antibody
      mediated rejection triggered by alloantibody binding and complement activation is
      recognized increasingly as a significant contribution to graft loss. Even though
      one component of the immune system may dominate and lead to rejection being
      described in short hand as T cell or antibody mediated, it is usually
      multifactorial resulting from the integration of multiple mechanisms. Identifying
      the molecular pathways that trigger tissue injury, signal transduction and
      rejection facilitates the identification of targets for the development of
      immunosuppressive drugs.

PMID- 22138819
TI  - Effect of prooxidants on yeast mitochondria.
AB  - Tightly coupled mitochondria from Yarrowia lipolytica and Dipodascus (Endomyces)
      magnusii yeasts were used in this study. The two yeasts are aerobes containing
      the fully competent respiratory chain with three energy conservation sites.
      Interaction of the yeast mitochondria with prooxidants (diamide, menadione,
      oxaloacetate, phenylarsine oxide, hydrogen peroxide, t-butyl peroxide, and
      ascorbate plus Fe(2+)) was studied. The prooxidants, depending on their chemical
      nature, either caused uncoupling (e.g., activated state 4 respiration) or
      inhibited oxidation of respiratory substrates. All of the agents dissipated the
      membrane potential without megachannel formation (no large-scale swelling of
      mitochondria was observed). Except for combined application of ascorbate and
      Fe(2+), the prooxidant-induced decrease in the membrane potential was
      specifically prevented by ATP, even in the cases when classic antioxidants, e.g.,
      N-acetylcysteine, were ineffective. No permeabilization of yeast mitochondria was
      observed under concerted action of prooxidants and Ca(2+), suggesting that an
      mPTP-like pore, if it ever occurs in yeast mitochondria, is not coupled with
      Ca(2+) uptake.

PMID- 22138820
TI  - A porous metal-organic framework with helical chain building units exhibiting
      facile transition from micro- to meso-porosity.
AB  - A metal-organic framework (MOF) with helical channels has been constructed by
      bridging helical chain secondary building units with 2,6-di-p-carboxyphenyl-4,4'
      bipyridine ligands. The activated MOF shows permanent porosity and gas adsorption
      selectivity. Remarkably, the MOF exhibits a facile transition from micro- to meso
      porosity.

PMID- 22138821
TI  - A linear complexity phasing method for thousands of genomes.
AB  - Human-disease etiology can be better understood with phase information about
      diploid sequences. We present a method for estimating haplotypes, using genotype
      data from unrelated samples or small nuclear families, that leads to improved
      accuracy and speed compared to several widely used methods. The method, segmented
      haplotype estimation and imputation tool (SHAPEIT), scales linearly with the
      number of haplotypes used in each iteration and can be run efficiently on whole
      chromosomes.

PMID- 22138822
TI  - Controlled gene expression in primary Lgr5 organoid cultures.
AB  - The study of gene function in endodermal epithelia such as of stomach, small
      intestine and colon relies heavily on transgenic approaches. Establishing such
      animal models is laborious, expensive and time-consuming. We present here a
      method based on Cre recombinase-inducible retrovirus vectors that allows the
      conditional manipulation of gene expression in primary mouse organoid culture
      systems.

PMID- 22138823
TI  - mGRASP enables mapping mammalian synaptic connectivity with light microscopy.
AB  - The GFP reconstitution across synaptic partners (GRASP) technique, based on
      functional complementation between two nonfluorescent GFP fragments, can be used
      to detect the location of synapses quickly, accurately and with high spatial
      resolution. The method has been previously applied in the nematode and the fruit
      fly but requires substantial modification for use in the mammalian brain. We
      developed mammalian GRASP (mGRASP) by optimizing transmembrane split-GFP carriers
      for mammalian synapses. Using in silico protein design, we engineered chimeric
      synaptic mGRASP fragments that were efficiently delivered to synaptic locations
      and reconstituted GFP fluorescence in vivo. Furthermore, by integrating molecular
      and cellular approaches with a computational strategy for the three-dimensional
      reconstruction of neurons, we applied mGRASP to both long-range circuits and
      local microcircuits in the mouse hippocampus and thalamocortical regions,
      analyzing synaptic distribution in single neurons and in dendritic compartments.

PMID- 22138824
TI  - High-efficiency counterselection recombineering for site-directed mutagenesis in
      bacterial artificial chromosomes.
AB  - Whereas bacterial artificial chromosomes (BACs) offer many advantages in studies
      of gene and protein function, generation of seamless, precisely mutated BACs has
      been difficult. Here we describe a counterselection-based recombineering method
      and its accompanying reagents. After identifying intramolecular recombination as
      the major problem in counterselection, we built a strategy to reduce these
      unwanted events by expressing Redbeta alone at the crucial step. We enhanced this
      method by using phosphothioated oligonucleotides, using a sequence-altered rpsL
      counterselection gene and developing online software for oligonucleotide design.
      We illustrated this method by generating transgenic mammalian cell lines carrying
      small interfering RNA-resistant and point-mutated BAC transgenes. Using this
      approach, we generated mutated TACC3 transgenes to identify phosphorylation
      specific spindle defects after knockdown of endogenous TACC3 expression. Our
      results highlight the complementary use of precisely mutated BAC transgenes and
      RNA interference in the study of cell biology at physiological expression levels
      and regulation.

PMID- 22138825
TI  - Bayesian localization microscopy reveals nanoscale podosome dynamics.
AB  - We describe a localization microscopy analysis method that is able to extract
      results in live cells using standard fluorescent proteins and xenon arc lamp
      illumination. Our Bayesian analysis of the blinking and bleaching (3B analysis)
      method models the entire dataset simultaneously as being generated by a number of
      fluorophores that may or may not be emitting light at any given time. The
      resulting technique allows many overlapping fluorophores in each frame and
      unifies the analysis of the localization from blinking and bleaching events. By
      modeling the entire dataset, we were able to use each reappearance of a
      fluorophore to improve the localization accuracy. The high performance of this
      technique allowed us to reveal the nanoscale dynamics of podosome formation and
      dissociation throughout an entire cell with a resolution of 50 nm on a 4-s
      timescale.

PMID- 22138826
TI  - Lipofuscin-like pigment in gonads of Sea Urchin Strongylocentrotus intermedius as
      a potential biomarker of marine pollution: a field study.
AB  - Accumulation of lipofuscin-like pigments (LLPs) has been shown to be an
      appropriate index of both age and stress in some aquatic invertebrates. In the
      present study, LLP was quantified by measuring its autofluorescence intensity (ex
      450 nm/em 512 nm) in nutritive phagocytes (NPs) of sea urchins Strongylocentrotus
      intermedius inhabiting polluted and relatively clean areas of Japan Sea. To avoid
      variations in LLP content related to sea urchin reproductive condition, only
      developing gonads with acini occupied mostly by NPs were used for LLP
      quantification as well as semiquantitative histopathological analysis. LLP
      concentrations ranged from 0.0 to 4.57 +/- 0.53% area fraction in female gonads
      and from 0.0 to 4.61 +/- 0.35% in male gonads. The presence of specimens with
      extremely high LLP concentrations (>1.5%) in all examined samples, including
      specimens from the reference station, as well as the absence of strong
      correlations between LLP concentrations and several parameters related to
      pollution (heavy-metal concentrations in sea urchin gonads and concentrations of
      heavy metals, DDT, hexachlorocyclohexane, and total petroleum hydrocarbons in
      sediments), allow us to conclude that LLP content in sea urchin NPs can not be
      used as a biomarker in marine pollution monitoring.

PMID- 22138827
TI  - [Detection of porcine Circovirus type 2 and Torque-Teno-Sus-virus 1 and 2 in
      semen samples of boars from an Austrian artificial insemination centre].
AB  - OBJECTIVE: Porcine circovirus type 2 (PCV-2) and torque-teno-sus- viruses (TTSuV)
      are ubiquitous in all pig-producing countries. Both pathogens are transmitted
      horizontally as well as vertically, and semen could be an important means of
      transmission. Aim of this study was the investigation of the prevalence of these
      two viruses in boar semen. MATERIAL AND METHODS: Single semen samples from 100
      boars from an artificial insemination centre were analysed by quantitative real
      time PCR for PCV2 and by conventional PCR for TTSuV-1 and TTSuV-2. RESULTS: Only
      one Pietrain boar of age of 47months showed a measurable PCV-2 quantity of
      7.56x103/ml semen. Four samples were PCR-positive for TTSuV-1, and five for TTVSu
      2, while in a single co-infection both TTSuVs were detected.All TTSuV-positive
      samples originated from Pietrain boars. CONCLUSION AND CLINICAL RELEVANCE: This
      study represents the first description of TTSuV presence in semen in Austria. The
      prevalence of TTSuV as well as PCV-2 was low. The clinical relevance of a
      simultaneous contamination of boar semen with both pathogens remains unclear.

PMID- 22138828
TI  - [Computed tomography of the pig lung. An innovative approach to the definition of
      the pulmonary health status].
AB  - OBJECTIVE: In veterinary medicine computed tomography (CT) imaging has gained
      importance in recent years, especially for diagnostics in pets, but also during
      the course of experimental studies in animal models for human medicine. In this
      study the applicability of CT as an imaging method for the depiction of the
      porcine thorax and in particular of the pig lung was evaluated. MATERIAL AND
      METHODS: CT examinations were performed with 11 healthy pigs of two age groups.
      For evaluation, CT findings were related to clinical, radiological,
      macroscopical, microscopical, and microbiological findings. RESULTS: Clinically
      relevant anatomical structures were determined and recorded using transverse
      slices. In ventral recumbency, lung parenchyma density measurements at the levels
      of the second, fourth and seventh thoracic vertebrae resulted in significantly
      higher densities of the ventral in comparison to those of the dorsal lung
      quadrants. CONCLUSION AND CLINICAL RELEVANCE: Computed tomography is a valuable
      tool for the high-contrast depiction of the porcine lung without superposition.
      In future studies this CT reference base for unaltered pig lungs may facilitate
      the identification of anatomical structures within the porcine lung as well as
      the assessment of pathological lung alterations.

PMID- 22138829
TI  - [Porcine eperythrozoonosis: from Eperythrozoon suis to Mycoplasma suis].
AB  - Mycoplasma suis  (formerly known as  Eperythrozoon suis ) is the most prevalent
      agent causing haemolytic anaemia in swine. The disease is also known as porcine
      eperythrozoonosis.  M.suis  is a small, pleomorphic bacteria parasitizing porcine
      erythrocytes. To date, no in vitro cultivation system for  M.suis  has been
      established and, therefore, our knowledge about the characteristics of  M.suis 
      and the pathogenesis of porcine eperythrozoonosis is rather limited.  M.suis  can
      cause acute disease, but the major significance of  M.suis  infections lies in
      the fact that  M.suis  can establish chronic and persistent infections leading to
      a higher susceptibility to other infections, especially of the respiratory and
      digestive tracts. The present article summarizes the current knowledge of the
      pathogen, the clinical signs and pathogenesis, diagnostic as well as therapy and
      prophylaxis.

PMID- 22138830
TI  - [Pyrrolizidine alkaloids and seneciosis in farm animals. Part 1: occurrence,
      chemistry and toxicology].
AB  - Pyrrolizidine alkaloids belong to a class of phytotoxins which are present in
      more than 6000 plant species. The disease seneciosis in farm animals represents
      the severe poisoning by pyrrolizidine alkaloids from plants of the genus 
      Senecio. This form of poisoning has been known since the end of the 19th century
      in Germany, the USA, Canada and New Zealand, and is mainly caused by  Senecio
      jacobaea  and related  Senecio  spp. in farm animals, including poultry. Animal
      poisoning by pyrrolizidine alkaloids is of worldwide importance. In Germany
      poisoning of horses and cattle by  Senecio jacobaea, which was earlier named
      Schweinsberg disease, is of renewed relevance for veterinary medicine. The
      disease occurs almost entirely as a consequence of chronic poisoning and in
      general ends fatally. The ultimate cause is the formation of toxic metabolites of
      pyrrolizidine alkaloids in the liver, and their covalent binding to nucleic acids
      and proteins leading to liver cirrhosis. Because many pyrrolizidine alkaloids
      possess mutagenic, and a few also carcinogenic properties, European and
      international authorities are concerned about possible residue levels in food of
      animal origin. The review addresses in its first part several aspects, being the
      occurrence, the chemistry, and the toxicology of pyrrolizidine alkaloids as well
      as animal intoxications by poisonous plants. In the second part (46) clinical
      characteristics of animal seneciosis, the therapeutic interventions, the
      significant species differences and a critical assessment of so-called nontoxic
      amounts of  Senecio  plants in animal fodder with reference to cumulative lethal
      toxin doses are presented.

PMID- 22138831
TI  - [First description of PCV-2-induced SMEDI-syndrome in Switzerland].

PMID- 22138832
TI  - [Multinodular pulmonary fibrosis in a horse from Schleswig-Holstein].

PMID- 22138833
TI  - [Licensed drugs for small ruminants].

PMID- 22138834
TI  - [Is milk yield in dairy cattle limited? Comments on physiological aspects].

PMID- 22138835
TI  - Further pay restrictions are a "bitter blow" to NHS staff, says BMA.

PMID- 22138836
TI  - Care of dying patients is improving, but access to palliative specialists varies.

PMID- 22138837
TI  - Texan clinic threatens UK bloggers with legal action over criticisms of its
      treatments.

PMID- 22138838
TI  - Care Quality Commission cuts inspections to meet deadlines for registration.

PMID- 22138839
TI  - Charities are disappointed with the voluntary nature of new agreement on aid.

PMID- 22138840
TI  - Obama champions new targets for treating and preventing HIV and AIDS.

PMID- 22138842
TI  - Endoscopic esophagitis is more severe in gastroesophageal reflux patients with a
      positive family history.
AB  - BACKGROUND: The role of genetic factors in the etiology of gastroesophageal
      reflux disease (GERD) is still uncertain. AIM: To define whether the presence of
      reflux symptoms in first-degree relatives can affect the severity of the
      endoscopic picture of patients with GERD and disease evolution during follow-up.
      PATIENTS/METHODS: A total of 1930 consecutive patients with GERD were referred
      for endoscopy from Trikala prefecture, had an entry endoscopy and a follow-up if
      needed. Before endoscopic evaluation, all patients and their first-degree
      relatives completed Reflux Symptom Questionnaire. Patients were followed up for 4
      years with Reflux Symptom Questionnaire every 6 months. RESULTS: A total of 258
      (62.9%) patients with positive and 724 (47.6%) with negative family history of
      GERD had esophagitis (P<0.0001). Seventy-six (74.5%) patients with more than 1
      family member with GERD had esophagitis (P<0.0001). During follow-up endoscopic
      picture was aggravated in 101 (25%) patients with positive and 46 (3%) with
      negative family history. A total of 359 (24%) of GERD patients with negative and
      24 (10%) with positive family history managed to stop proton pump inhibitors
      during follow-up (P<0.0001). In logistic regression analysis: age, male sex,
      presence of hiatal hernia, family history of GERD, tranquilizer use, frequency,
      and duration of reflux symptoms were independently associated with presence of
      esophagitis. CONCLUSIONS: Although we cannot overlook the importance of
      confounding factors such as body weight and/or psychological factors, we found
      that endoscopic picture is more severe among GERD patients with at least 1 first
      degree relative with GERD. During follow-up, patients with negative family
      history had more chances to wean off proton pump inhibitors after life-style
      modifications.

PMID- 22138841
TI  - The relationship between immigration and mental health: what is the role of
      workplace psychosocial factors.
AB  - BACKGROUND: To study the relationship between immigration and mental health
      considering the psychosocial factors in the workplace. METHODS: Multistage
      cluster sampling was used (final sample: 7,612 workers). Workers whose country of
      origin was unknown were excluded from the study (study population: 7,555). The
      information was collected between 2004 and 2005 using a standardized
      questionnaire, and interviews were conducted in respondents' homes. The risk of
      poor mental health according to psychosocial factor, using the native, non
      exposed workers as a reference, was calculated using log-binomial models. The
      prevalence ratio (PR) and confidence intervals (CI 95%) were estimated from crude
      data and from data adjusted for sex, age, and occupational category. RESULTS:
      Immigrants who experienced high quantitative demands (PR = 1.46; CI 95%:1.34
      1.59), high emotional demands (PR = 1.42; CI 95%:1.301.56), high demands for
      hiding emotions (PR = 1.35; CI 95%:1.21-1.50), low possibilities for development
      (PR = 1.21; CI 95%:1.09-1.33), low levels of support from coworkers (PR = 1.41;
      CI 95%:1.30-1.53), and low esteem (PR = 1.53; CI 95%:1.42-1.66) perceived worse
      mental health. Equally, the study found that the immigrants with a high influence
      (PR = 1.19; CI 95%:1.09-1.29) and high control over working times (PR = 1.25; CI
      95%:1.14-1.36) also reported worse mental health. We also found that native
      workers exposed to these factors also perceived worse mental health than those
      who were not exposed and that even, at times, they were at greater risk than
      exposed immigrants. CONCLUSIONS: Differences in mental health between exposed and
      non-exposed wage earners, whether immigrant or native workers, indicate the
      importance of taking action to reduce psychosocial factors, as this would benefit
      both native and immigrant workers.

PMID- 22138843
TI  - Risk of bacterial colonization of pancreatic stents used in endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND: Pancreatic stents (PSs) are commonly inserted at the time of
      endoscopic retrograde cholangiopancreatography to reduce the risk of
      pancreatitis. If left in situ for more than 2 weeks, they have been associated
      with pancreatic duct injury. The mechanism of this injury is not clear, but it
      may be related to bacterial colonization. AIM: : To determine the incidence of PS
      colonization by microorganisms and the relationship between such colonization and
      the type, length, diameter, and duration of PSs in situ. METHODS: A series of
      endoscopic retrograde cholangiopancreatographies performed by a single operator
      in a tertiary referral centre during which a PS was placed was analysed. In each
      case, after removing the PS, the segment of the PS, which had been intraluminal,
      was sent for microbiological analysis. Microscopy and culture results were
      compared with stent length (cm), time in situ (d), demographic information, and
      clinical course. RESULTS: Of the 47 PSs sent for culture, 28 grew clinically
      significant bacteria. The majority of organisms cultured were of the Klebsiella,
      Escherichia, Enterobacter, and Enterococcus genera. Time in situ was found to
      correlate strongly with the growth of clinically significant organisms using a
      logarithmic regression analysis tool (coefficient=0.36, change of variance=6.43,
      P=0.01). In addition, 1 patient developed Enterobacter septicaemia almost
      certainly related to stent colonization, which necessitated urgent removal of the
      stent 10 days after insertion. CONCLUSION: Colonization of PSs by pathogenic
      organisms is common and related to duration in situ of the PS. Enteric organisms
      are frequently implicated. Although significant clinical sequelae are infrequent,
      we suggest that PSs should not be left in situ for >7 to 10 days due to the
      significant risk of bacterial colonization.

PMID- 22138844
TI  - Serological tests in gluten sensitivity (nonceliac gluten intolerance).
AB  - GOALS: To characterize the serological pattern of gluten sensitivity (GS) and to
      compare it with that found in celiac disease. BACKGROUND: GS has recently been
      identified as a new clinical entity included in the spectrum of gluten-related
      disorders, but it is still lacking of diagnostic markers. STUDY: Sera from 78
      patients with GS and 80 patients with celiac disease were retrospectively
      assessed for immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG
      deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase
      antibodies (tTGA), and IgA endomysial antibodies (EmA). RESULTS: IgG AGA were
      positive in 56.4% of GS patients and in 81.2% of celiac patients, with high
      antibody titers in both groups. IgA AGA were detected in 7.7% of GS patients and
      in 75% of celiac patients, showing lower enzyme-linked immunosorbent assay
      activities in GS than those found in celiac disease. Only 1 of the 78 patients
      with GS was positive for IgG DGP-AGA (detected in 88.7% of patients with celiac
      disease). IgA tTGA and IgA EmA were negative in all GS patients, whereas their
      positivity in celiac patients was 98.7% and 95%, respectively. Patients with GS
      displayed a variegated clinical picture with intestinal and extraintestinal
      symptoms (abdominal pain, bloating, diarrhea, constipation, foggy mind,
      tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms,
      depression, and anemia) together with normal or mildly abnormal small intestinal
      mucosa. CONCLUSIONS: The serological pattern of GS is characterized by IgG AGA
      positivity in more than half of cases associated to IgA AGA in a few patients,
      but without EmA, tTGA, and DGP-AGA, which are the specific markers of celiac
      disease.

PMID- 22138845
TI  - Endoscopic and imaging findings in protein-losing enteropathy.
AB  - OBJECTIVES: Protein-losing enteropathy (PLE) is often difficult to diagnose. We
      evaluated the diagnostic yields of underlying diseases of PLE among
      esophagogastroduodenoscopy, colonoscopy, fluoroscopic conventional enteroclysis
      (FCE), videocapsule endoscopy (VCE), and double-balloon enteroscopy (DBE) and
      prognosis after treatment. METHODS: Between June 2003 and August 2010, 25
      consecutive patients with PLE confirmed by fecal alpha1-antitrypsin clearance
      (n=18) and technetium 99m human serum albumin scintigraphy (n=19) were enrolled,
      investigated, and treated. RESULTS: Of 25 patients, 4 (16%) with intestinal
      lymphangiectasia secondary to macroglobulinemia (n=1), amyloidosis (n=2), and
      strongyloidiasis (n=1) were diagnosed at preceding esophagogastroduodenoscopy or
      colonoscopy, and 7 (32%) with primary intestinal lymphangiectasia and chronic
      nonspecific multiple ulcers unrelated to nonsteroidal anti-inflammatory drugs of
      the small intestine were newly diagnosed at FCE or VCE. Other 11 (44%) patients
      with primary intestinal lymphangiectasia, small-bowel tumors, amyloidosis,
      chronic nonspecific multiple ulcers unrelated to nonsteroidal anti-inflammatory
      drugs of the small intestine, Crohn's disease, and small-bowel ulcers due to
      polyarteritis nodosa were diagnosed only at DBE with biopsy. Three patients with
      primary intestinal lymphangiectasia, cirrhosis after living donor liver
      transplantation, and congestive heart failure were not diagnosed at any small
      bowel examination. The overall diagnostic yield of FCE, VCE, and DBE was 62%
      (8/13), 83% (14/17), and 88% (22/25), respectively. Eight patients (32%) died of
      underlying disorders regardless of medical treatment over the follow-up period.
      CONCLUSIONS: DBE with pathologic findings of biopsy specimens was useful for the
      differential diagnosis of PLE. Noninvasive VCE might be preferable and useful for
      screening and follow up of PLE without stricture. Prognosis of a subgroup of PLE
      was poor regardless of treatment.

PMID- 22138846
TI  - New-onset diabetes patients need pancreatic cancer screening?
AB  - OBJECTIVE: Because patients with new-onset diabetes mellitus (DM) have a
      significantly increased likelihood of association with pancreatic cancer, we need
      to select the subgroup of diabetic patients who have more chance of association
      with pancreatic cancer. METHODS: We retrospectively reviewed medical records of
      case group (151 patients with pancreatic cancer with new-onset DM) and control
      group (302 patients with new-onset DM without cancer). RESULTS: Compared with the
      control group, pancreatic cancer group were older, had more weight loss, lower
      usual body mass index (BMI), more family history of pancreatic cancer (3.3% vs.
      0.7%; P=0.044), and had less family history of DM (13.9% vs. 37.4%; P<0.001). If
      a new-onset DM patient did not have family history of DM, he was of age older
      than or equal to 65 years or had weight loss of >2 kg or had premorbid usual BMI
      <25 kg/m(2), pancreatic cancer associated DM could be discriminated from new
      onset type 2 DM with 80.8% sensitivity, 67.6% specificity, 2.5% and 99.7% of
      positive and negative predictability for pancreatic cancer, respectively.
      CONCLUSIONS: Among patients who meet criteria for diabetes within 2 years, those
      who are elderly, have lower premorbid BMI, weight loss, no family history of DM,
      need screening of pancreatic cancer.

PMID- 22138847
TI  - In vivo evaluation of a metronidazole-containing gel for the adjuvant treatment
      of chronic periodontitis: preliminary results.
AB  - The present study developed an experimental metronidazole-based gel and evaluated
      its efficacy for the adjuvant treatment of chronic periodontitis. Sixteen
      patients were randomly allocated into two groups of eight subjects according to
      the following proposed treatments: (1) scaling and root planing (active control)
      or (2) scaling and root planing and direct periodontal intrapocket application of
      15% metronidazole-based gel in two sites (>=5 mm in depth) (experimental group).
      Potential changes in the subgingival microbiota were assessed using a DNA
      Checkerboard method at three proposed times: baseline and following 7 or 30 days
      of drug administration. High-performance liquid chromatography (HPLC) monitored
      metronidazole concentrations in the crevicular fluid during treatment. The
      metronidazole experimental group presented lower bacterial counts than the
      control group at the three evaluated times (p<0.01 for baseline, p<0.001 for 7 or
      30 days) when the target species were analyzed as a pool of bacteria. Samples
      revealed significantly lower counts 7 days after drug administration compared
      with baseline or after 30 days (p<0.05). HPLC analysis detected gel 1 h after
      application. The metronidazole-based gel significantly decreased the total
      bacterial count at the three evaluated times. Periodontopathogenic species were
      not different after gel administration.

PMID- 22138848
TI  - Promoting calcium and vitamin D intake to reduce the risk of osteoporosis in men
      on androgen deprivation therapy for recurrent prostate cancer.
AB  - PURPOSE: The aim of this study was to measure the impact of a patient education
      intervention aimed at increasing dietary intake of calcium and vitamin D in
      patients currently on androgen deprivation therapy (ADT) for the treatment of
      prostate cancer. METHODS: Sixty-one participants attended a one-time dietitian
      delivered group education session focusing on diet and lifestyle strategies to
      reduce the risk of bone loss while on ADT. Dietary intake was assessed using the
      diet history questionnaire at baseline and again at approximately 1 year post
      intervention. Demographics, medical history (including comorbidities), awareness
      of developing bone loss while on ADT, and information resources utilized were
      recorded at baseline. RESULTS: Fifty-one participants completed both time points.
      Over one third of men did not meet minimum current clinical guidelines for
      calcium or vitamin D intake at baseline. Sixty-three percent of men reported they
      were aware that osteoporosis was a known side effect of ADT therapy. Only
      supplemental calcium intake was significantly increased after the intervention.
      Men aware of their risk of developing bone loss while on ADT reported higher
      baseline calcium intake (p <= 0.05). Men undergoing ADT for less than 1 year at
      the time of intervention had significantly higher total calcium intake at follow
      up compared to men on ADT for longer than 1 year (p = 0.038). Nonsignificant
      trends indicated that calcium and vitamin D intakes changed to a greater degree
      in those undergoing ADT for less than 1 year as well. CONCLUSIONS: Total calcium
      and vitamin D did not change significantly as a result of the intervention.
      Results suggest that promotion of dietary changes may be more effective if
      delivered closer to the initiation of therapy.

PMID- 22138849
TI  - A systematic review and meta-analysis of anti-pseudomonal penicillins and
      carbapenems in pediatric febrile neutropenia.
AB  - PURPOSE: Carbapenems represent a broad-spectrum alternative to anti-pseudomonal
      penicillin (APP) combination or single-agent therapy for the management of
      pediatric febrile neutropenia (FN). Our primary objective was to describe the
      risk of treatment failure in children treated with an APP or carbapenem as
      initial empiric treatment for FN. Our secondary objective was to compare outcomes
      of APP versus carbapenem therapy in this population. METHODS: An electronic
      search of Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled
      Trials was performed. We limited studies to prospective pediatric trials of FN in
      which at least one treatment arm consisted of an APP (with or without an
      aminoglycoside) or a carbapenem. RESULTS: Of 7,281 articles reviewed, 27 studies
      comprising 30 treatment regimens were included for meta-analysis. Treatment
      failure, including antibiotic modification, occurred in 41% (95% confidence
      interval (CI) 32-50%), 34% (95% CI 27-41%), and 35% (95% CI 24-45%) of patients
      treated with APP-aminoglycoside, APP monotherapy, and carbapenem monotherapy
      regimens, respectively. There was no significant difference in treatment failure
      including antibiotic modification, infection-related mortality, or adverse events
      when comparing either APP regimen with carbapenem monotherapy. Although a limited
      number of studies were available, when stratified by FN risk group, no
      differences were seen in any outcome. CONCLUSIONS: Our meta-analysis suggests
      that APP-aminoglycoside, APP monotherapy, and carbapenem monotherapy are all
      efficacious therapeutic options for the empiric management of pediatric FN.

PMID- 22138852
TI  - Designed synthesis of uniformly sized iron oxide nanoparticles for efficient
      magnetic resonance imaging contrast agents.
AB  - Various magnetic nanoparticles have been extensively investigated as novel
      magnetic resonance imaging (MRI) contrast agents owing to their unique
      characteristics, including efficient contrast effects, biocompatibility, and
      versatile surface functionalization capability. Nanoparticles with high
      relaxivity are very desirable because they would increase the accuracy of MRI.
      Recent progress in nanotechnology enables fine control of the size, crystal
      structure, and surface properties of iron oxide nanoparticles. In this tutorial
      review, we discuss how MRI contrast effects can be improved by controlling the
      size, composition, doping, assembly, and surface properties of iron-oxide-based
      nanoparticles.

PMID- 22138850
TI  - Copy number variation in the domestic dog.
AB  - Differences in the content and organization of DNA, collectively referred to as
      structural variation, have emerged as a major source of genetic and phenotypic
      diversity within and between species. In addition, structural variation provides
      an important substrate for evolutionary innovations. Here, we review recent
      progress in characterizing patterns of canine structural variation within and
      between breeds, and in correlating copy number variants (CNVs) with phenotypes.
      Because of the extensive phenotypic diversity that exists within and between
      breeds and the tantalizing examples of canine CNVs that influence traits such as
      skin wrinkling in Shar-Pei, dorsal hair ridge in Rhodesian and Thai Ridgebacks,
      and short limbs in many breeds such as Dachshunds and Corgis, we argue that
      domesticated dogs are uniquely poised to contribute novel insights into CNV
      biology. As new technologies continue to be developed and refined, the field of
      canine genomics is on the precipice of a deeper understanding of how structural
      variation and CNVs contribute to canine genetic diversity, phenotypic variation,
      and disease susceptibility.

PMID- 22138851
TI  - Needs assessment of individuals with serious mental illness: can it help in
      promoting recovery?
AB  - Needs of individuals with serious mental illness (SMI) must be understood in
      order to promote recovery. This study examined the needs of 206 individuals with
      SMI and compared their perceptions with those of their professional caregivers.
      Needs were reported in the areas of accommodations, psychotic symptoms, daytime
      activity, intimate relationships, and psychological distress. Caregivers reported
      more met needs, while individuals themselves reported more unmet needs. Results
      suggest that in order to promote recovery, services for persons with SMI should
      be developed in accordance with patients' most prominent needs, specifically in
      the social and personal areas of intimate and sexual relationships.

PMID- 22138853
TI  - High-flow hemodialysis arteriovenous shunt with concurrent central vein stenosis
      masquerading as sigmoid sinus dural arteriovenous fistula.

PMID- 22138854
TI  - Total synthesis of antimalarial diterpenoid (+)-kalihinol A.
AB  - Total synthesis of antimalarial diterpenoid (+)-kalihinol A, isolated from marine
      sponge Acanthella sp., is achieved. This total synthesis involves regioselective
      alkylation of an epoxide, construction of a tetrahydropyran ring by iodo
      etherification, construction of a cis-decalin ring by intramolecular Diels-Alder
      reaction, isomerization of cis-decalin to trans-decalin, and subsequent
      functionalization of the trans-decalin ring.

PMID- 22138855
TI  - Phytochrome B control of total leaf area and stomatal density affects drought
      tolerance in rice.
AB  - We report that phytochrome B (phyB) mutants exhibit improved drought tolerance
      compared to wild type (WT) rice (Oryza sativa L. cv. Nipponbare). To understand
      the underlying mechanism by which phyB regulates drought tolerance, we analyzed
      root growth and water loss from the leaves of phyB mutants. The root system
      showed no significant difference between the phyB mutants and WT, suggesting that
      improved drought tolerance has little relation to root growth. However, phyB
      mutants exhibited reduced total leaf area per plant, which was probably due to a
      reduction in the total number of cells per leaf caused by enhanced expression of
      Orysa;KRP1 and Orysa;KRP4 (encoding inhibitors of cyclin-dependent kinase complex
      activity) in the phyB mutants. In addition, the developed leaves of phyB mutants
      displayed larger epidermal cells than WT leaves, resulting in reduced stomatal
      density. phyB deficiency promoted the expression of both putative ERECTA family
      genes and EXPANSIN family genes involved in cell expansion in leaves, thus
      causing greater epidermal cell expansion in the phyB mutants. Reduced stomatal
      density resulted in reduced transpiration per unit leaf area in the phyB mutants.
      Considering all these findings, we propose that phyB deficiency causes both
      reduced total leaf area and reduced transpiration per unit leaf area, which
      explains the reduced water loss and improved drought tolerance of phyB mutants.

PMID- 22138856
TI  - Isolation of C11 compounds and a cyclopropane fatty acid from an Okinawan
      ascidian, Diplosoma sp.
AB  - Pentylphenols 1 and 2, cyclopropane fatty acid 3, and cyclopentenones 4 and 5,
      were isolated from an ascidian, Diplosoma sp. The structures of 1-5 were
      determined by spectroscopic analysis and/or synthesis. Compound 1 inhibited the
      division of fertilized sea urchin eggs and compound 4 showed mild cytotoxity
      against HCT116 cells (human colorectal cancer cell).

PMID- 22138857
TI  - Inhibitors of testosterone biosynthetic and metabolic activation enzymes.
AB  - The Leydig cells of the testis have the capacity to biosynthesize testosterone
      from cholesterol. Testosterone and its metabolically activated product
      dihydrotestosterone are critical for the development of male reproductive system
      and spermatogenesis. At least four steroidogenic enzymes are involved in
      testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1) for
      the conversion of cholesterol into pregnenolone within the mitochondria, 3beta
      hydroxysteroid dehydrogenase (HSD3B), for the conversion of pregnenolone into
      progesterone, 17alpha-hydroxylase/17,20-lyase (CYP17A1) for the conversion of
      progesterone into androstenedione and 17beta-hydroxysteroid dehydrogenase
      (HSD17B3) for the formation of testosterone from androstenedione. Testosterone is
      also metabolically activated into more potent androgen dihydrotestosterone by two
      isoforms  5alpha-reductase 1 (SRD5A1) and 2 (SRD5A2) in Leydig cells and
      peripheral tissues. Many endocrine disruptors act as antiandrogens via directly
      inhibiting one or more enzymes for testosterone biosynthesis and metabolic
      activation. These chemicals include industrial materials (perfluoroalkyl
      compounds, phthalates, bisphenol A and benzophenone) and pesticides/biocides
      (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz) and plant
      constituents (genistein and gossypol). This paper reviews these endocrine
      disruptors targeting steroidogenic enzymes.

PMID- 22138858
TI  - Evaluation of the antioxidant potential of Salvia miltiorrhiza ethanol extract in
      a rat model of ischemia-reperfusion injury.
AB  - The present study was undertaken to evaluate the protection potential of ethanol
      extract of Salvia miltiorrhiza (SMEE) against oxidative injury in the ischemia
      reperfusion (I/R) model of rats in vivo. Rats were divided into six groups of 10
      rats each. Group I/R model and sham were fed with a standard rat chow, groups
      SMEE I and SMEE II were fed with a standard rat chow and 400 or 800 mg/kg b.w.
      ethanol extract for 12 days before the beginning of I/R studies. Positive control
      group was fed with a standard rat chow and salvianolic acid B (55 mg/kg b.w.) or
      tanshinone II-A (55 mg/kg b.w.) for 12 days before the beginning of I/R studies.
      To produce I/R, the left anterior descending artery (LAD) was occluded in
      anesthetized rats for 15 min, followed by 120 min reperfusion. Infarct sizes were
      found significantly decreased in SMEE-treated and positive control groups
      compared to I/R model group. Serum AST, LDH and CK-MB activities were
      significantly reduced and myocardium Na+-K+ ATPase, Ca2+-Mg2+ ATPase activities
      and antioxidant enzyme activities (SOD, CAT, GSH-Px) were markedly increased in
      SMEE-treated and salvianolic acid B or tanshinone II-A positive control groups
      compared to the I/R model group. Pretreatment of S. miltiorrhiza ethanol extract
      and salvianolic acid B or tanshinone II-A dose-dependently reduced significantly
      myocardium MDA level, ROS and NOS activities and enhanced myocardium GSH level in
      I/R rats compared to I/R rats model. In conclusion, we clearly demonstrated that
      S. miltiorrhiza ethanol extract pretreatment can decrease oxidative injury in
      rats subjected to myocardial I/R.

PMID- 22138859
TI  - Use of the metabolomics approach to characterize Chinese medicinal material
      Huangqi.
AB  - Integration of the genetic and metabolic fingerprinting can provide a new
      approach to differentiate similar Traditional Chinese Medical (TCM) materials.
      Two leguminous plants, Mojia Huangqi and Menggu Huangqi, are important medical
      herbs and share great similarities in morphology, chemical constituent, and
      genomic DNA sequence. The taxonomy of Mojia Huangqi and Menggu Huangqi has been
      debated for more than 50 years and discrimination of TCM materials directly
      affects the pharmacological and clinical effects. AFLP based genetic
      fingerprinting and GC-TOF/MS-based metabolic fingerprinting were used to
      successfully discriminate the two species. The results of AFLP supported the
      opinion that Menggu Huangqi was a variant of Mojia Huangqi. The metabolic
      fingerprinting showed growth locations have greater impacts on the metabolite
      composition and quantity than the genotypes (cultivated versus wild) in Menggu
      Huangqi. The difference of some soluble sugars, fatty acids, proline, and
      polyamine reflected plant adaptation to different growth environments. Using
      multivariate and univariate statistical analysis, three AFLP markers and eight
      metabolites were identified as candidate DNA and metabolic markers to distinguish
      the two herb materials. The correlation network between AFLP markers and
      metabolites revealed a complex correlation network, which indicated the special
      metabolic pathways and the regulation networks of Huangqi.

PMID- 22138860
TI  - A comparative miRNAome analysis reveals seven fiber initiation-related and 36
      novel miRNAs in developing cotton ovules.
AB  - An increasing number of microRNAs (miRNAs) have been shown to play crucial
      regulatory roles in the process of plant development. Here, we used high
      throughput sequencing combined with computational analysis to characterize
      miRNAomes from the ovules of wild-type upland cotton and a fiberless mutant
      during fiber initiation. Comparative miRNAome analysis combined with northern
      blotting and RACE-PCR revealed seven fiber initiation-related miRNAs expressed in
      cotton ovules and experimentally validated targets of these miRNAs are involved
      in different cellular responses and metabolic processes, including
      transcriptional regulation, auxin and gibberellin signal transduction, actin
      bundles, and lignin biosynthesis. This paper describes a complex regulatory
      network consisting of these miRNAs expressed in cotton ovules to coordinate fiber
      initiation responses. In addition, 36 novel miRNAs and two conserved miRNAs were
      newly identified, nearly doubling the number of known cotton miRNA families to a
      total of 78. Furthermore, a chromatin remodeling complex subunit and a pre-mRNA
      splicing factor are shown for the first time to be miRNA targets. To our
      knowledge, this study is the first systematic investigation of fiber initiation
      related miRNAs and their targets in the developing cotton ovule, deepening our
      understanding of the important regulatory functions of miRNAs in cotton fiber
      initiation.

PMID- 22138861
TI  - Mechanically controlled molecular orbital alignment in single molecule junctions.
AB  - Research in molecular electronics often involves the demonstration of devices
      that are analogous to conventional semiconductor devices, such as transistors and
      diodes, but it is also possible to perform experiments that have no parallels in
      conventional electronics. For example, by applying a mechanical force to a
      molecule bridged between two electrodes, a device known as a molecular junction,
      it is possible to exploit the interplay between the electrical and mechanical
      properties of the molecule to control charge transport through the junction. 1,4'
      Benzenedithiol is the most widely studied molecule in molecular electronics, and
      it was shown recently that the molecular orbitals can be gated by an applied
      electric field. Here, we report how the electromechanical properties of a 1,4'
      benzenedithiol molecular junction change as the junction is stretched and
      compressed. Counterintuitively, the conductance increases by more than an order
      of magnitude during stretching, and then decreases again as the junction is
      compressed. Based on simultaneously recorded current-voltage and conductance
      voltage characteristics, and inelastic electron tunnelling spectroscopy, we
      attribute this finding to a strain-induced shift of the highest occupied
      molecular orbital towards the Fermi level of the electrodes, leading to a
      resonant enhancement of the conductance. These results, which are in agreement
      with the predictions of theoretical models, also clarify the origins of the long
      standing discrepancy between the calculated and measured conductance values of
      1,4'-benzenedithiol, which often differ by orders of magnitude.

PMID- 22138862
TI  - Control over topological insulator photocurrents with light polarization.
AB  - Three-dimensional topological insulators represent a new quantum phase of matter
      with spin-polarized surface states that are protected from backscattering. The
      static electronic properties of these surface states have been comprehensively
      imaged by both photoemission and tunnelling spectroscopies. Theorists have
      proposed that topological surface states can also exhibit novel electronic
      responses to light, such as topological quantum phase transitions and spin
      polarized electrical currents. However, the effects of optically driving a
      topological insulator out of equilibrium have remained largely unexplored
      experimentally, and no photocurrents have been measured. Here, we show that
      illuminating the topological insulator Bi(2)Se(3) with circularly polarized light
      generates a photocurrent that originates from topological helical Dirac fermions,
      and that reversing the helicity of the light reverses the direction of the
      photocurrent. We also observe a photocurrent that is controlled by the linear
      polarization of light and argue that it may also have a topological surface state
      origin. This approach may allow the probing of dynamic properties of topological
      insulators and lead to novel opto-spintronic devices.

PMID- 22138863
TI  - Solid-state memories based on ferroelectric tunnel junctions.
AB  - Ferroic-order parameters are useful as state variables in non-volatile
      information storage media because they show a hysteretic dependence on their
      electric or magnetic field. Coupling ferroics with quantum-mechanical tunnelling
      allows a simple and fast readout of the stored information through the influence
      of ferroic orders on the tunnel current. For example, data in magnetic random
      access memories are stored in the relative alignment of two ferromagnetic
      electrodes separated by a non-magnetic tunnel barrier, and data readout is
      accomplished by a tunnel current measurement. However, such devices based on
      tunnel magnetoresistance typically exhibit OFF/ON ratios of less than 4, and
      require high powers for write operations (>1 * 10(6) A cm(-2)). Here, we report
      non-volatile memories with OFF/ON ratios as high as 100 and write powers as low
      as ~1 * 10(4) A cm(-2) at room temperature by storing data in the electric
      polarization direction of a ferroelectric tunnel barrier. The junctions show
      large, stable, reproducible and reliable tunnel electroresistance, with
      resistance switching occurring at the coercive voltage of ferroelectric
      switching. These ferroelectric devices emerge as an alternative to other
      resistive memories, and have the advantage of not being based on voltage-induced
      migration of matter at the nanoscale, but on a purely electronic mechanism.

PMID- 22138864
TI  - Label-free imaging of semiconducting and metallic carbon nanotubes in cells and
      mice using transient absorption microscopy.
AB  - As interest in the potential biomedical applications of carbon nanotubes
      increases, there is a need for methods that can image nanotubes in live cells,
      tissues and animals. Although techniques such as Raman, photoacoustic and near
      infrared photoluminescence imaging have been used to visualize nanotubes in
      biological environments, these techniques are limited because nanotubes provide
      only weak photoluminescence and low Raman scattering and it remains difficult to
      image both semiconducting and metallic nanotubes at the same time. Here, we show
      that transient absorption microscopy offers a label-free method to image both
      semiconducting and metallic single-walled carbon nanotubes in vitro and in vivo,
      in real time, with submicrometre resolution. By using appropriate near-infrared
      excitation wavelengths, we detect strong transient absorption signals with
      opposite phases from semiconducting and metallic nanotubes. Our method separates
      background signals generated by red blood cells and this allows us to follow the
      movement of both types of nanotubes inside cells and in the blood circulation and
      organs of mice without any significant damaging effects.

PMID- 22138865
TI  - Imaging of a primitive clitoral epidermoid cyst.
AB  - An 11-year-old Caucasian girl was investigated for a clitoromegaly that had
      increased in size over 5 weeks. Clitoromegaly is a rare condition in childhood.
      Among nonhormonal causes are tumours, both benign and malignant. Evaluation of
      the adrenal glands and ovaries was performed by US. An epidermoid cyst was
      suggested by MRI including diffusion-weighted imaging, and this was confirmed
      histopathologically.

PMID- 22138866
TI  - The effects of carbohydrate intake and muscle glycogen content on self-paced
      intermittent-sprint exercise despite no knowledge of carbohydrate manipulation.
AB  - The aim of this study was to determine the effects of carbohydrate (CHO)
      ingestion and muscle glycogen content, without the influence of knowledge of CHO
      consumption, on intermittent-sprint performance. Ten males completed two
      conditions on two consecutive days. Day 1 involved 2 * 40 min of leg cycling
      separated by 15 min of arm cycling, followed by an overnight diet consuming
      either a high [HCHO; 7 g/kg body weight (bw)] or low (LCHO; 2 g/kg bw) CHO diet.
      Participants were blinded to the knowledge CHO was being examined or manipulated.
      Day 2 included a 60-min intermittent-sprint exercise (ISE) protocol that included
      15-m maximal sprints every minute and self-paced efforts of varying intensities.
      Pre and post-ISE muscle biopsies were obtained on Day 2. Pre- and post-exercise
      maximal voluntary torque (MVT), voluntary activation (VA) and twitch contractile
      properties were assessed during 15 maximal isometric contractions. Blood glucose
      and lactate, heart rate (HR) and rating of perceived exertion (RPE) were also
      recorded. Pre-ISE muscle glycogen was greater in HCHO compared with LCHO (597 +/-
      115 vs. 318 +/- 72 mmol kg dry weight; P = 0.001). Total distance and hard
      running distance were 4.9 and 8.1% greater in HCHO, respectively (P = 0.02-0.04).
      Peak MVT, VA, HR and RPE were not different between conditions (P > 0.05). Blood
      glucose was higher pre-ISE for LCHO but lower post-ISE compared with HCHO (P <
      0.05). These results indicate HCHO improved self-paced exercise intensities
      during the ISE protocol despite no knowledge of dietary manipulation. Due to the
      blinded study design, exercise intensities seem manipulated due to peripheral
      perturbations associated with CHO content rather than a conscious manipulation of
      exercise intensities.

PMID- 22138869
TI  - The changing face of scholarship.

PMID- 22138867
TI  - Peripheral augmentation index as a biomarker of vascular aging: an invasive
      hemodynamics approach.
AB  - We compared two measures of vascular function obtained from digital volume
      waveforms with measures of target organ damage and novel invasive measures of
      vascular function as they relate to vascular aging. Aortic pulse pressure
      amplification, pulsatility, form factor and extent of coronary atherosclerosis
      (modified Gensini score) were obtained invasively in 59 patients undergoing left
      heart catheterization. Digital volume waveforms were captured via peripheral
      arterial tone (PAT) and used to derive augmentation index (AIx) and the pulse
      wave amplitude-reactive hyperemia index (PWA-RHI). AIx was associated with age (r
      = 0.50, p < 0.05) and aortic pulsatility (r = 0.45, p < 0.05) and inversely
      associated with estimated glomerular filtration rate (-0.29, p < 0.05) aortic
      pulse pressure amplification (r = -0.28, p < 0.05) and aortic form factor (r = 
      0.38, p < 0.05). AIx was slightly higher in patients with left ventricular
      hypertrophy (LVH) versus those without left ventricular hypertrophy (30 vs. 14%,
      p = 0.058). There was no association between AIx and Gensini score. PWA-RHI was
      not associated with age, estimated glomerular filtration rate or invasive
      vascular parameters and did not differ in patients with versus without LVH (p =
      ns). PWA-RHI was inversely associated with Gensini score (r = -0.32, p < 0.05).
      AIx derived from PAT is correlated with age-associated changes in vascular
      function and target organ damage but not coronary atherosclerotic burden. PWA-RHI
      is associated with coronary atherosclerotic burden but is not associated with
      target organ damage or other measures of vascular aging assessed in this study.
      Each parameter provides distinct insight into systemic vascular aging and target
      organ damage.

PMID- 22138868
TI  - Scaling lower-limb isokinetic strength for biological maturation and body size in
      adolescent basketball players.
AB  - The relationships between knee joint isokinetic strength, biological maturity
      status and body size were examined in 14-16-year-old basketball players,
      considering proportional allometric modeling. Biological maturity status was
      assessed with maturity offset protocol. Stature, body mass, sitting height, and
      estimated thigh volume were measured by anthropometry. Maximal moments of force
      of concentric and eccentric muscular actions for the knee extensors and flexors
      were assessed by isokinetic dynamometry at 60 degrees  s(-1). Regression analysis
      revealed a linear relation between maximal moments of force of the knee extensors
      in both muscular actions and knee flexors in concentric actions were moderately
      high (0.55 <= r <= 0.64). As for knee flexors in eccentric actions, a squared
      term of maturity indicator was significant indicating that the relationship with
      maturity offset tended to plateau approximately 2 years after PHV. Incorporating
      maturity indicator term with body size term (body mass or thigh volume) in the
      allometric models revealed that the size exponents for both body mass and thigh
      volume were reduced compared with simple allometric modeling. The results
      indicate a significant inter-individual variation in lower-limb isokinetic
      strength performance at 60 degrees  s(-1) in concentric and eccentric muscular
      actions in late adolescent basketball players. The variability in performance is
      related to inter-individual variation in estimated time before or after peak
      height velocity, as well as differences in body size. Proportional allometric
      models indicate that the influence of estimated time from age at peak height
      velocity on isokinetic strength performance is mostly mediated by corresponding
      changes in overall body mass.

PMID- 22138870
TI  - Financing physical therapy doctoral education: methods used by entry-level
      students and the financial impact after graduation.
AB  - With the move to the doctor of physical therapy (DPT) degree and increasing
      tuition costs, there is concern about financing entry-level education. The
      purposes of this study were to identify how students finance their DPT education
      and to describe the financial impact after graduation. METHODS: A written survey
      was used to collect data on financing DPT education, student debt, and the
      financial impact on graduates. There were 92 subjects who had graduated from one
      program. Frequencies as well as nonparametric statistics using cross-tabulations
      and chi-squared statistics were calculated. RESULTS: The response rate was 55%.
      Of the respondents, 86% had student loans, 66% worked during school, 57% received
      some family assistance, and 21% had some scholarship support. The amount of
      monthly loan repayment was not statistically related to the ability to save for a
      house, the ability to obtain a loan for a house or car, or the decision to have
      children. Saving for the future (p = 0.016) and lifestyle choices (p = 0.035)
      were related to the amount of monthly loan repayment. DISCUSSION: Major sources
      of funding were student loans, employment income, and/or family assistance.
      Respondent's ability to save for the future and lifestyle choices were negatively
      impacted when loan debt increased. Physical therapist education programs should
      consider offering debt planning and counseling.

PMID- 22138871
TI  - Physician assistants in orthopedic practice. A national study.
AB  - Orthopedics is the third most common specialty practiced by physician assistants
      (PAs), but little is known at a national level about PAs backgrounds or specific
      contributions to orthopedic practices. We sought to describe, from a nationally
      representative sample, the demographic and practice characteristics of PAs
      working in orthopedics. METHODS: Surveys were sent to 1,200 PAs, identified from
      American Academy of Physician Assistants data, who reported orthopedics as their
      specialty between 2005 and 2007. Information was collected on demographic and
      educational background, PA training, current practice characteristics, clinical
      activities, and physician supervision. RESULTS: After three mailings, the
      adjusted response rate was 55.8%. Of respondents, 45% reported working in general
      orthopedics, and the remainder in orthopedic specialties. A majority (76.5%)
      completed a 4- to 8-week rotation in orthopedic surgery during PA school, but
      most did not complete any advanced postgraduate orthopedic training. Orthopedic
      group practices were the most commonly reported employer type (57.6% of
      respondents). Respondents performed an average of 59 outpatient visits per week
      and 16 inpatient visits per week. A large proportion (87.6%) participated in
      surgery on a regular basis, most often working as first assistants. Many
      orthopedic generalists and specialists performed a broad range of clinical
      activities, including ones suggestive of general, rather than close and direct,
      physician supervision such as closing surgical incisions independently and taking
      first call. CONCLUSIONS: PAs contribute to orthopedic care in many inpatient and
      outpatient settings and perform a wide variety of clinical tasks, often with only
      general supervision and little or no formal postgraduate training. Health
      workforce planning and the development of appropriate training models for PAs in
      orthopedics and other medical and surgical specialties require understanding the
      content of PA specialty practice.

PMID- 22138872
TI  - Construct validity of the Health Science Reasoning Test.
AB  - The aim of this study was to evaluate the construct validity of the Health
      Science Reasoning Test (HSRT) by determining if the test could discriminate
      between expert and novice physical therapists' critical-thinking skills. METHODS:
      Experts identified from a random list of certified clinical specialists and
      students in the first year of their physical therapy education from two physical
      therapy programs completed the HSRT. RESULTS: Experts (n = 73) had a higher total
      HSRT score (mean 24.06, SD 3.92) than the novices (n = 79) (mean 22.49, SD 3.2),
      with the difference being statistically significant t (148) = 2.67, p = 0.008.
      CONCLUSION: The HSRT total score discriminated between expert and novice critical
      thinking skills, therefore establishing construct validity. To our knowledge,
      this is the first study to compare expert and novice performance on a
      standardized test. The opportunity to have a tool that provides evidence of
      students' critical thinking skills could be helpful for educators and students.
      The test results could aid in identifying areas of students' strengths and
      weaknesses, thereby enabling targeted remediation to improve critical thinking
      skills, which are key factors in clinical reasoning, a necessary skill for
      effective physical therapy practice.

PMID- 22138873
TI  - An investigation of the family practicum experience. Family and student
      perspectives.
AB  - Professional occupational therapy (OT) and physical therapy (PT) programs
      traditionally instruct students using volunteers, including children who have
      disabilities. Presenting a child before a classroom of students may deprive the
      child of dignity and may limit students' understanding of the child's disability
      and the importance of family-centered service delivery. An alternative approach
      that respects the child's privacy and promotes dignity is student observation in
      the context of the child's daily living. The Family Practicum Intervention Plan
      assignment (FPIP), part of the professional Neuro Rehab course, was created to
      facilitate students' understanding of a child with a disability while maintaining
      child dignity and family-centered values. This descriptive study explored,
      through two online surveys, the experiences of the OT and PT students and the
      families of children who participated in the FPIP. Additionally, the study
      investigated the influences of this participation on students' perceptions of
      family life and views of childhood disability. Overall, students and families
      perceived this assignment to be a good learning experience because it allowed the
      student to work within a real-life scenario and it gave the families an expert
      "voice" in the education of OT and PT students. The positive comments provided by
      the families and students and the desire of families to recommend the FPIP
      experience to other families suggest the value of the learning assignment. When
      developing OT and PT professional pediatric coursework, instructors should
      include assignments that take place in the child's natural environment to offer
      meaningful learning that maintains the dignity of the child.

PMID- 22138874
TI  - Improving families' nutrition knowledge through service learning.
AB  - Current research documents an increasing prevalence of pediatric obesity in the
      United States. Effective nutrition education programs are needed to affect this
      trend. This study pre-tested and post-tested kindergarten students and their
      families to evaluate the impact of a service learning nutrition education
      program. Changes in nutrition knowledge and home environment among kindergarten
      students and their parents who participated in a nutrition education program
      (treatment group) were compared with those who did not participate in the program
      (control group). The nutrition education program was developed and delivered by
      senior nutrition majors at an accredited 4-year university. Responses from a
      total of 156 parents and kindergarten children (treatment n = 79, control n = 77)
      out of 205 total kindergarten families (76% response rate) were analyzed to
      compare changes in knowledge and home environment. Results indicate an increase
      in the kindergarten children's knowledge and a decrease in the family's home
      obesigenic risk. These results provide support for the use of service learning to
      provide age-appropriate nutrition education programs to benefit the entire
      family.

PMID- 22138875
TI  - Use of a virtual environment to facilitate instruction of an interprofessional
      home assessment.
AB  - Technology has become a ubiquitous part of our society and is largely embedded in
      today's educational system. 3D virtual reality technology can be used to simulate
      environments and activities and may be used as an instructional technology. The
      purpose of this research was to better understand the utility of a web-based
      virtual environment as a teaching tool to represent clinical assessment and
      interventions in the home environment. Specifically, students' learning outcomes
      related to interprofessional collaboration, patient-centered decision-making, and
      appreciation of the environmental and social context of functional mobility and
      occupational performance will be described through descriptive analysis. Thirty
      four physical therapist students and 35 occupational therapist students
      participated in an instructor-guided virtual assessment of a client's function in
      a home environment utilizing a virtual environment, Second Life(r). Teams
      formulated task-specific, functional client goals and home modification
      recommendations. Students revisited a solution virtual environment to view and
      evaluate recommendations in a follow-up instructor-guided tour. Students
      completed a web-based survey capturing student perception of the experience. Team
      assignments were analyzed based on a rubric representing learning objectives.
      Descriptive analysis was conducted on the survey. Assignment analysis revealed
      contextual and client-centered recommendations. Student surveys revealed that
      students found the virtual environment supportive of learning. Student surveys
      and reflection statements were supportive of the interprofessional collaboration.
      Use of a virtual environment in instruction allows an authentic means of
      representing interprofessional home assessment. The virtual environment allowed a
      temporal depiction of home environment issues and solutions providing the unique
      opportunity for students to evaluate home recommendations.

PMID- 22138876
TI  - Care of the elderly from an international and multiprofessional perspective. Web
      based learning.
AB  - In the future, an increased number of the elderly with their vulnerability
      related to aging will demand more multidisciplinary and innovative approaches
      toward their care. A course called "Care of the Elderly from a European
      Perspective" has been developed in collaboration among several European
      universities with the aim of providing an opportunity for students to increase
      their mutual understanding of elder care. The course is based on phenomenographic
      research and collaborative learning as a pedagogical approach. Learning should be
      thought of as an active research and problem-solving process, to which
      interaction and dialogue are central. The technical learning environment is based
      on software and web conferences through which students and teachers can
      communicate one-to-one or as a group. By working together in international
      groups, students learn to analyze differences among countries: How do cultural,
      social, economic, and geographical circumstances affect the quality of life? They
      also learn to understand ways in which different health professionals can
      cooperate better in the care of the elderly.

PMID- 22138877
TI  - Precepting the medical assistant practicum: expectations and rewards: an
      evaluation of preceptors' opinions.
AB  - This study investigated the opinions of preceptors on select topics relevant to
      the benefits and rewards of precepting medical assisting (MA) students. METHODS:
      A 35-item questionnaire was distributed to volunteer MA preceptors over the
      course of 1 year. Survey items prompted participants for information concerning
      background and previous experiences with MA students, as well as gathered
      opinions on the benefits, issues, and rewards of preceptorships. RESULTS: Of the
      preceptors who gave evidence of their credentials, 98.43% were either practicing
      certified medical assistants (CMA-AAMA) or nurses. Respectively, 80.85% of CMAs
      and 80.00% of nurses felt that students provided the office with extra help and
      placed no financial burden on the practice. Approximately 44% ranked free
      continuing medical education (CME) credits as the most important reward. Written
      responses identified thank-you notes as an important demonstration of service,
      acknowledgment, and appreciation. CONCLUSION: MA preceptors consider students a
      beneficial aspect of their practice because they lighten strenuous workloads and
      stimulate preceptors to remain current in their professional fields.
      Noncompensated MA preceptors value both extrinsic (e.g., free CME credits) and
      intrinsic rewards (e.g., feedback and thank-you cards) and suggested that
      intrinsic rewards were of greater value.

PMID- 22138878
TI  - Implementing U.S. federal health reform: learning from the Israeli experience.
AB  - The purpose of the Federal Health Care Reform signed into law in the United
      States in March 2010 was to create a fundamental change in the configuration of
      national health care and to bring about significant improvements in health care
      quality and costs. Interpretation and implementation of the laws and regulations
      enacted will have a direct bearing on the reform's potential success. However, it
      is not always possible to predict eventual developments. This paper demonstrates
      some possible unanticipated implications of the health care reform, based on the
      Israeli experience. While the US reform is yet in its initial stages, it is
      suggested that health care policy makers and implementers learn from the Israeli
      experience and embrace its lessons.

PMID- 22138879
TI  - Impact of a community-based exercise program on children and adolescents with
      disabilities.
AB  - The purpose of this study was to determine if participation in a community-based
      fitness program improves: a) strength and endurance, b) self-concept and quality
      of life, and c) positive social interactions among participants with
      disabilities. Nineteen children completed the study (10 experimental group, 9
      control group). Pre/post testing included body mass index (BMI), energy
      expenditure index (EEI), Presidential Fitness Test (PFT), strength testing using
      a handheld dynamometer, PedsQL, and the Piers-Harris 2 Self-Concept Scale (PH-2).
      The experimental group participated in an 8-week exercise program two times per
      week and were given a home exercise program (HEP). No statistically significant
      differences were observed in BMI, EEI, PFT, strength, quality of life, or self
      concept. A statistically significant difference in social interactions was found
      between the first and second half of the exercise program while the children
      performed group activities and ran track based on repeated measures MANOVA at
      p<0.05. While changes in fitness may not be observed following an 8-week exercise
      program, improvements in social interactions may be possible.

PMID- 22138880
TI  - Learning is in the facilitation: faculty perspectives with facilitated teaching
      and learning-recommendations from informal discussions.
AB  - Small group learning is an interactive activity that requires a skilled teacher
      with the ability to facilitate and debrief. Approximately 250 students from seven
      health professions were enrolled in a first year interprofessional education
      course that focused on the importance of communication and collaboration. Weekly
      faculty debrief sessions were conducted and were utilized to share the teachers
      perspectives with facilitative teaching as well as for feedback and improvement
      strategies. Recommendations included linking the learning within the small group
      sessions back to clinical and professional practice in order to validate the
      course content and thereby increase student engagement; creation of facilitator
      guides with specific debrief instructions for the given objectives in order to
      encourage effective learning dialogue among all participants; and providing
      faculty with formalized facilitator training as well as debrief strategies in
      order to attain the skills to better guide student learning.

PMID- 22138881
TI  - Use of learning styles to enhance graduate education.
AB  - This study was carried out to help occupational therapy students utilize learning
      strategies necessary to be successful at the graduate level. Students completed
      The Kolb Learning Style Inventory and Motivation Strategies for Learning
      Questionnaire to identify their personal learning preferences. These preferences
      were used as the basis for a remediation program carried out during the second
      semester of the curriculum following less than adequate performance during the
      first semester in basic science content. At mid-term, all but one student was
      satisfied with her performance in neuroanatomy. Following a closer scrutiny of
      the dissatisfied student's approach to learning, the student and program
      developer devised a more comprehensive plan. By the end of the semester, all
      students successfully passed neuroanatomy while adequately balancing other
      courses within the semester. Given the initial positive results, the utilization
      of attention to learning styles as a means to direct student learning may be a
      promising model for struggling students in graduate education.

PMID- 22138882
TI  - Clinical impact of body mass index on the outcome of the SPARC-sling system for
      the treatment of female stress urinary incontinence.
AB  - PURPOSE: Of this observational study was to evaluate the clinical outcome of the
      suprapubic arc (SPARC)-sling system in women with stress urinary incontinence
      according to body mass index (BMI). MATERIALS AND METHODS: A total of 151 women
      underwent SPARC between June 2001 and March 2009 at a single tertiary academic
      center. A complete urodynamic investigation was performed preoperatively. A
      minimum follow-up of 12 months was required, which left data of 93 individuals
      for analyses. Participants were divided into the following: A, non-obese (BMI
      18.5 to <25 kg/m(2)), B, overweight (BMI 25 to <30 kg/m(2)), and C, obese (BMI 30
      35 kg/m(2)). Objective and subjective cure rates, as well as overall success rate
      and self-perceived severity of bother, were measured. Moreover, participants were
      asked about their satisfaction after surgery. RESULTS: Median follow-up was 7.6
      years. Mean number of pads/day, pad test, and self-perceived severity of bother
      were significantly reduced overall, as well as in each BMI category (P < 0.001).
      In multivariable analyses, BMI was not an independent predictor of objective cure
      rate, coded either as continuous (P = 0.108) or as categorical variable (P for
      trend 0.301). Similarly, BMI was not an independent predictor of subjective cure
      rate, both coded as continuous (P = 0.475) and as categorical variable (P for
      trend 0.690). Overall, 92% (A), 85% (B), and 80% (C) of participants were
      satisfied with the surgical outcome at follow-up, respectively. CONCLUSIONS: BMI
      failed to achieve independent predictor status regarding objective and subjective
      cure rate at follow-up. A high BMI is not a contraindication to SPARC, more
      studies are recommended to confirm these findings.

PMID- 22138885
TI  - Defining moments in genetic counselor professional development: one decade later.

PMID- 22138884
TI  - Effect of low-level laser therapy on cochlear hair cell recovery after gentamicin
      induced ototoxicity.
AB  - Cochlear hair cells are the sensory receptors of the auditory system. It is well
      established that antibiotic drugs such as gentamicin can damage hair cells and
      cause hearing loss. Rescuing hair cells after ototoxic injury is an important
      issue in hearing recovery. Although many studies have indicated a positive effect
      of low-level laser therapy (LLLT) on neural cell survival, there has been no
      study on the effects of LLLT on cochlear hair cells. Therefore, the aim of this
      study was to elucidate the effects of LLLT on hair cell survival following
      gentamicin exposure in organotypic cultures of the cochlea of rats. The cochlea
      cultures were then divided into a control group (n = 8), a laser-only group (n =
      8), a gentamicin-only group (n = 8) and a gentamicin plus laser group (n = 7).
      The control cultures were allowed to grow continuously for 11 days. The laser
      only cultures were irradiated with a laser with a wavelength of 810 nm at 8
      mW/cm(2) for 60 min per day (0.48 J/cm(2)) for 6 days. The gentamicin groups were
      exposed to 1 mM gentamicin for 48 h and allowed to recover (gentamicin-only
      group) or allowed to recover with daily irradiation (gentamicin plus laser
      group). The hair cells in all groups were stained with FM1-43 and counted every 3
      days. The number of hair cells was significantly larger in the gentamicin plus
      laser group than in the gentamicin-only group. The number of hair cells was
      larger in the laser-only group than in the control group, but the difference did
      not reach statistical significance. These results suggest that LLLT may promote
      hair cell survival following gentamicin damage in the cochlea. This is the first
      study in the literature that has demonstrated the beneficial effect of LLLT on
      the recovery of cochlear hair cells.

PMID- 22138886
TI  - Losing sight.

PMID- 22138883
TI  - Head-down posture induces PERG alterations in early glaucoma.
AB  - PURPOSE: To probe susceptibility of retinal ganglion cells (RGC) to physiological
      stressors associated with moderate head-down body tilt in patients with suspicion
      of glaucoma or early manifest glaucoma (EMG). METHODS: One hundred nine subjects
      with best corrected visual acuity (BCVA) >= 20/20 and no disease other than
      glaucoma [glaucoma suspects (GS)=79, EMG=14, normal controls (NC)=16 and
      comparable age range were tested. Noncontact intraocular pressure (IOP), pattern
      electroretinogram (PERG), and brachial blood pressure/heart rate measurements
      were performed in 3 consecutive conditions (~0038 min apart): seated (baseline), 
      10-degree whole body head-down tilt (HDT), and seated again (recovery). PERG
      amplitude and latency, IOP, and systolic/diastolic blood pressures, heart rate,
      calculated mean central retinal artery pressure, ocular perfusion pressure, and
      systolic/diastolic perfusion pressures were evaluated. RESULTS: During HDT, IOP
      significantly (P<0.001) increased in all groups approximately to the same extent
      (approximately 20%). PERG amplitude did not change in NC but decreased
      significantly (P<0.001) in patients (GS, -25%, EMG -23%). PERG phase become
      delayed in NC (-1.6%, P=0.04) but more so in patients (GS, -2.7%, P<0.001; EMG, 
      6.0%, P<0.001). The proportion of patients with PERG alterations significantly
      (P<0.05) exceeding those occurring in age-adjusted and baseline-adjusted NC were,
      GS: amplitude 20%, phase 15%; EMG: amplitude 14%, phase 50%. All measures
      recovered baseline values after HDT. CONCLUSIONS: Moderate HDT induces temporary
      worsening of RGC function in a subpopulation of GS and EMG patients. This
      noninvasive protocol may help disclose abnormal susceptibility of RGCs in a
      subset of the patients at risk of glaucoma.

PMID- 22138887
TI  - Postpartum depression: is it mood disorder or medical condition?

PMID- 22138888
TI  - Learning to say no.

PMID- 22138889
TI  - Counseling adolescents and the challenges for genetic counselors.
AB  - Genetic counselors may have an important role in helping the adolescent make an
      informed decision with regard to genetic testing and in helping them to adjust to
      genetic risk information. However, counseling techniques that are used with
      adults may not be always be suited to the adolescent population. Adolescence is a
      time of development during which separation from the family and formation of
      identity is achieved. The process of this development may impact the genetic
      counseling relationship. Family relationships may have a strong influence on the
      client's decision to have genetic testing. Additionally, it may be difficult to
      engage the client as adolescents may not have the ability to think abstractly and
      consider the short and long term consequences of genetic testing. It is helpful
      therefore to discuss the counseling process and techniques that may be useful
      when counseling these clients. This paper presents two case studies that
      illustrate some of the difficulties that may occur when counseling adolescents
      for genetic testing. The authors' have reflected on their clinical experience
      with these clients and this is presented here to add to the growing literature on
      this subject.

PMID- 22138890
TI  - Aboriginal community-centered injury surveillance: a community-based
      participatory process evaluation.
AB  - While injuries are a leading health concern for Aboriginal populations, injury
      rates and types vary substantially across bands. The uniqueness of Aboriginal
      communities highlights the importance of collecting community-level injury
      surveillance data to assist with identifying local injury patterns, setting
      priorities for action and evaluating programs. Secwepemc First Nations
      communities in British Columbia, Canada, implemented the Injury Surveillance
      Project using the Aboriginal Community-Centered Injury Surveillance System. This
      paper presents findings from a community-based participatory process evaluation
      of the Injury Surveillance Project. Qualitative data collection methods were
      informed by OCAP (Ownership, Control, Access, and Possession) principles and
      included focus groups, interviews and document review. Results focused on lessons
      learned through the planning, implementation and management of the Injury
      Surveillance Project identifying lessons related to: project leadership and
      staff, training, project funding, initial project outcomes, and community
      readiness. Key findings included the central importance of a community-based and
      paced approach guided by OCAP principles, the key role of leadership and project
      champions, and the strongly collaborative relationships between the project
      communities. Findings may assist with successful implementation of community
      based health surveillance in other settings and with other health issues and
      illustrate another path to self-determination for Aboriginal communities. The
      evaluation methods represent an example of a collaborative community-driven
      approach guided by OCAP principles necessary for work with Aboriginal
      communities.

PMID- 22138891
TI  - Ten-year prospective follow-up of histological changes at five points on the
      gastric mucosa as recommended by the updated Sydney system after Helicobacter
      pylori eradication.
AB  - BACKGROUND: Atrophic gastritis and intestinal metaplasia (IM) are well known as
      precancerous lesions of gastric cancer. The present study evaluated the gastric
      mucosa for 10 years after H. pylori eradication at five points of the stomach as
      recommended by the updated Sydney system to clarify the relationship between H.
      pylori eradication and gastric cancer prevention. METHODS: Among the comprised
      373 patients, 323 were H. pylori-positive while 50 patients were H. pylori
      negative. Patients with successful eradication underwent follow-up endoscopic
      examination every year. Biopsy specimens were taken from five points of the
      stomach, as recommended by the updated Sydney system, and were evaluated for the
      degree of gastritis prospectively. RESULTS: Two hundred ninety-four out of the
      323 H. pylori-positive patients successfully achieved eradication. Of the 197
      patients on whom five-point biopsy was performed, the courses of 30 patients were
      able to be observed every year for 10 years after successful eradication.
      Inflammation, activity, and atrophy score at all five points were significantly
      reduced half a year to 6 years after eradication. IM scores fluctuated intensely
      up and down during all observation periods; however, IM score of the lesser
      curvature of the corpus continued decreasing gradually and showed a significant
      decrease 6 years after (0.97 +/- 0.09 to 0.42 +/- 0.17, P < 0.05). CONCLUSION: In
      10 years after H. pylori eradication, atrophy at all sites and IM in the lesser
      curvature of the corpus gradually and significantly decreased. These results
      suggest that the improvement of gastric atrophy and IM might have association
      with the reduction of gastric cancer occurrence.

PMID- 22138892
TI  - Use of nucleofection to efficiently transfect primary rabbit lacrimal gland
      acinar cells.
AB  - Lacrimal gland acinar cells are an important cell type to study due to their role
      in production and release of tear proteins, a function essential for ocular
      surface integrity and normal visual acuity. However, mechanistic studies are
      often limited by problems with transfection using either plasmid DNA or siRNA.
      Although various gene delivery methods are available, many have been unproductive
      due to consistently low transfection efficiencies. We have developed a method
      using nucleofection that can result in 50% transfection efficiency and 60%
      knockdown efficiency for plasmid DNA and siRNA, respectively. These results are
      vastly improved relative to previous studies, demonstrating that nucleofection
      offers an efficient transfection technique for primary lacrimal gland acinar
      cells.

PMID- 22138894
TI  - Redox mediation enabled by immobilised centres in the pores of a metal-organic
      framework grown by liquid phase epitaxy.
AB  - A layer of a metal-organic framework (SURMOF) was prepared on a thiol monolayer
      on Au. Charge transport across the insulating membrane could be established by
      using ferrocene as an immobilised redox mediator. Reversibility of the
      immobilisation and its role in the electrode kinetics are discussed.

PMID- 22138893
TI  - Spinal dysraphism associated with the cutaneous lumbosacral infantile hemangioma:
      a neuroradiological review.
AB  - BACKGROUND: Spinal dysraphism is suspected in patients with midline
      abnormalities, especially in those with lumbosacral cutaneous markings. A recent
      prospective study demonstrated that isolated cutaneous infantile hemangiomas (IH)
      of the lumbosacral region have one of the highest risks (relative risk of 438) of
      associated spinal dysraphism. OBJECTIVE: The specific types of dysraphism and
      radiological findings associated with cutaneous IH of the lumbosacral region have
      not been described in detail, to the best of our knowledge. The aim of this
      multicenter study is to retrospectively classify types of spinal anomalies
      associated with the cutaneous lumbosacral IH. MATERIALS AND METHODS: The
      radiological images of 20 cases of lumbosacral infantile hemangioma associated
      with spinal dysraphism were reviewed. RESULTS: Tethered cord was found in 60% of
      the 20 cases, spinal lipoma was present in 50% and 45% had intraspinal
      hemangiomas. Sinus tract was found in 40% of the children. CONCLUSION: A range of
      spinal anomalies is associated with cutaneous lumbosacral infantile hemangiomas
      and MRI can be used to characterize these abnormalities.

PMID- 22138895
TI  - Employment status and work-related problems of gastrointestinal cancer patients
      at diagnosis: a cross-sectional study.
AB  - Objective To assess the employment status of patients with gastrointestinal
      cancer at diagnosis and to examine work-related problems of employed patients. 
      Design New, consecutive patients were included at the Gastrointestinal Oncology
      Center Amsterdam, a one-stop, rapid access diagnostic assessment centre. Patients
      were interviewed on their employment status by a nurse. If (self-) employed,
      patients were asked to self-report on work-related problems, perceived distress
      (0-10), cancer-related problems, fatigue (MFI-20, range 4-20) and work ability
      (three WAI questions, range 0-10).  Results Of all 333 included new consecutive
      patients (age range 32-89 years), 95 patients (28%) were (self-) employed at time
      of diagnosis, 179 (54%) were pensioners, and 59 were not working (18%). For the
      assessment of work-related problems, 45 (47%) of these 95 employed patients with
      cancer participated. Their mean age was 56 years, and patients had
      oesophageal/stomach (49%), colorectal (18%) or hepatic/pancreatic/biliary cancer
      (33%). Half of the employed patients (49%) were still at work, while 51% were on
      sick leave. The main reasons for sick leave were stress (35%), (scheduled)
      operation (26%), fatigue (17%) and pain (13%). Most patients on sick leave (70%)
      had no contact with their own occupational physician, although the majority (67%)
      would like to continue to work. Work-related problems were experienced by 73% of
      working patients. The mean work ability was 5.4, the mean general fatigue score
      was 11.5, and the mean distress score was 4.7. Employed patients on sick leave
      reported a lower work ability, more fatigue and higher distress but no more
      cancer-related problems compared with those still working.  Conclusion A quarter
      of all patients with gastrointestinal cancer seen at an oncological centre are
      employed at time of diagnosis, and of these employed patients, 73% experience
      work-related problems. During diagnosis and treatment, information and support on
      work-related issues should be offered to patients with cancer as an essential
      part of high-quality oncological care.

PMID- 22138896
TI  - New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands:
      potential anti-trypanosomal agents.
AB  - In the search for new therapeutic tools against neglected diseases produced by
      trypanosomatid parasites, and particularly against African Trypanosomiasis, whose
      etiological agent is Trypanosoma brucei, organoruthenium compounds with bioactive
      nitrofuran containing thiosemicarbazones (L) as co-ligands were obtained. Four
      ruthenium(II) complexes with the formula [Ru(2)(p-cymene)(2)(L)(2)]X(2), where X
      = Cl or PF(6), were synthesized and the crystal structures of two of them were
      solved by X-ray diffraction methods. Two of the complexes show significant in
      vitro growth inhibition activity against Trypanosoma brucei brucei and are highly
      selective towards trypanosomal cells with respect to mammalian cells (J774 murine
      macrophages). These promising results make the title organoruthenium compounds
      good lead candidates for further developments towards potential antitrypanosomal
      organometallic drugs.

PMID- 22138897
TI  - Robust control of CPG-based 3D neuromusculoskeletal walking model.
AB  - This paper proposes a method for enhancing the robustness of the central pattern
      generator (CPG)-based three-dimensional (3D) neuromusculoskeletal walking
      controller. The CPG has been successfully applied to walking controllers and
      controllers for walking robots. However, the robustness of walking motion with
      the CPG-based controller is not sufficient, especially when subjected to external
      forces or environmental variations. To achieve a realistic and stable walking
      motion of the controller, we propose the use of an attracting controller in
      parallel with the CPG-based controller. The robustness of the proposed controller
      is confirmed through simulation results.

PMID- 22138898
TI  - Genetic causes of spermatogenic failure.
AB  - Approximately 10%-15% of couples are infertile, and a male factor is involved in
      almost half of these cases. This observation is due in part to defects in
      spermatogenesis, and the underlying causes, including genetic abnormalities,
      remain largely unknown. Until recently, the only genetic tests used in the
      diagnosis of male infertility were aimed at detecting the presence of
      microdeletions of the long arm of the Y chromosome and/or chromosomal
      abnormalities. Various other single-gene or polygenic defects have been proposed
      to be involved in male fertility. However, their causative effects often remain
      unproven. The recent evolution in the development of whole-genome-based
      techniques and the large-scale analysis of mouse models might help in this
      process. Through knockout mouse models, at least 388 genes have been shown to be
      associated with spermatogenesis in mice. However, problems often arise when
      translating this information from mice to humans.

PMID- 22138899
TI  - Male sexual dysfunction and infertility associated with neurological disorders.
AB  - Normal sexual and reproductive functions depend largely on neurological
      mechanisms. Neurological defects in men can cause infertility through erectile
      dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major
      conditions contributing to these symptoms are pelvic and retroperitoneal surgery,
      diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord
      injury. Erectile dysfunction can be managed by an increasingly invasive range of
      treatments including medications, injection therapy and the surgical insertion of
      a penile implant. Retrograde ejaculation is managed by medications to reverse the
      condition in mild cases and in bladder harvest of semen after ejaculation in more
      severe cases. Anejaculation might also be managed by medication in mild cases
      while assisted ejaculatory techniques including penile vibratory stimulation and
      electroejaculation are used in more severe cases. If these measures fail,
      surgical sperm retrieval can be attempted. Ejaculation with penile vibratory
      stimulation can be done by some spinal cord injured men and their partners at
      home, followed by in-home insemination if circumstances and sperm quality are
      adequate. The other options always require assisted reproductive techniques
      including intrauterine insemination or in vitro fertilization with or without
      intracytoplasmic sperm injection. The method of choice depends largely on the
      number of motile sperm in the ejaculate.

PMID- 22138900
TI  - Updates on the relation of weight excess and reproductive function in men: sleep
      apnea as a new area of interest.
AB  - Obesity has a negative effect on male reproductive function. It is associated
      with low testosterone levels and alteration in gonadotropin secretion. Male
      obesity has been linked to reduced male fertility. Data regarding the relation of
      obesity to sperm parameters are conflicting in terms of the nature and magnitude
      of the effect. New areas of interest are emerging that can help explain the
      variation in study results, such as genetic polymorphism and sleep apnea. Sleep
      disorders have been linked to altered testosterone production and hypogonadism in
      men. It was also correlated to erectile dysfunction. The relation of sleep
      disorders to male fertility and sperm parameters remains to be investigated. Men
      with hypogonadism and infertility should be screened for sleep apnea. Treatment
      of obesity and sleep apnea improves testosterone levels and erectile function.

PMID- 22138901
TI  - Energy restriction and exercise modulate angiopoietins and vascular endothelial
      growth factor expression in the cavernous tissue of high-fat diet-fed rats.
AB  - The purpose of the current study was to evaluate the effect of a high-fat (HF)
      diet, energy restriction and exercise on the expression of vascular endothelial
      growth factor (VEGF), angiopoietin (Ang) 1 and 2, and their receptors in rat
      corpus cavernosum (CC). Male Wistar rats were fed ad libitum with an HF diet for
      8 or 16 weeks. After 8 weeks of the HF diet, a group of rats was subjected to
      energy restriction with or without exercise for 8 weeks. Control animals had free
      access to standard diet for the same period. After euthanasia, blood was
      collected and the penises removed for immunofluorescence assays (VEGF, VEGF
      receptor (VEGFR) 1 and 2, Ang1, Ang2 and Tie2) and semiquantification of VEGF,
      VEGFR1, VEGFR2, Ang1, Ang2, Tie2, endothelial nitric oxide synthase (eNOS) and
      Akt/phospho-Akt by Western blotting. HF diet-fed rats exhibited lower high
      density lipoprotein cholesterol (HDL-c) levels, higher systolic blood pressure
      and an increased atherogenic index. A significant increase in Ang2 expression in
      the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway
      was activated by the HF diet. Energy restriction and exercise increased eNOS
      expression and restored most HF diet-induced modifications except for VEGFR2
      expression. These results emphasize the role of diet on vascular function
      regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2
      systems occurs before serum lipid changes and obesity onset, antedating
      structural atherosclerotic features.

PMID- 22138902
TI  - New understandings of the genetic basis of isolated idiopathic central
      hypogonadism.
AB  - Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized
      by delayed/absent puberty and/or infertility due to an insufficient stimulation
      of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone
      (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle
      stimulating hormone (FSH) levels may be observed in the affected patients, the
      term idiopathic central hypogonadism (ICH) appears to be more appropriate. This
      disease should be distinguished from central hypogonadism that is combined with
      other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is
      fivefold more prevalent in males. ICH frequently appears in a sporadic form, but
      several familial cases have also been reported. This finding, in conjunction with
      the description of numerous pathogenetic gene variants and the generation of
      several knockout models, supports the existence of a strong genetic component.
      ICH may be associated with several morphogenetic abnormalities, which include
      osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann
      syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has
      been generally considered to be a distinct subgroup. However, the description of
      several pedigrees, which include relatives who are affected either with isolated
      osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that
      ICH is a complex genetic disease that is characterized by variable expressivity
      and penetrance. In this context, either multiple gene variants or environmental
      factors and epigenetic modifications may contribute to the variable disease
      manifestations. We review the genetic mechanisms that are presently known to be
      involved in ICH pathogenesis and provide a clinical overview of the 227 cases
      that have been collected by the collaborating centres of the Italian ICH Network.

PMID- 22138903
TI  - Mechanisms and clinical correlates of sperm DNA damage.
AB  - Among the different DNA anomalies that can be present in the male gamete, DNA
      fragmentation is the most frequent, particularly in infertile subjects. There is
      now consistent evidence that a sperm containing fragmented DNA can be alive,
      motile, morphologically normal and able to fertilize an oocyte. There is also
      evidence that the oocyte is able to repair DNA damage; however, the extent of
      this repair depends on the type of DNA damage present in the sperm, as well as on
      the quality of the oocyte. Thus, it is important to understand the possible
      consequences of sperm DNA fragmentation (SDF) for embryo development,
      implantation, pregnancy outcome and the health of progeny conceived, both
      naturally and by assisted reproductive technology (ART). At present, data on the
      consequences of SDF for reproduction are scarce and, in many ways, inconsistent.
      The differences in study conclusions might result from the different methods used
      to detect SDF, the study design and the inclusion criteria. Consequently, it is
      difficult to decide whether SDF testing should be carried out in fertility
      assessment and ART. It is clear that there is an urgent need for the
      standardisation of the methods and for additional clinical studies on the impact
      of SDF on ART outcomes.

PMID- 22138905
TI  - Barrett esophagus: Need for ongoing surveillance called into question for
      patients with non-dysplastic Barrett esophagus.

PMID- 22138906
TI  - Biliary tract: Dendritic cells activate natural killers in biliary atresia.

PMID- 22138907
TI  - Cancer: CRC screening--cost effectiveness of fecal immunochemical tests.

PMID- 22138904
TI  - Sperm preparation: state-of-the-art--physiological aspects and application of
      advanced sperm preparation methods.
AB  - For assisted reproduction technologies (ART), numerous techniques were developed
      to isolate spermatozoa capable of fertilizing oocytes. While early methodologies
      only focused on isolating viable, motile spermatozoa, with progress of ART,
      particularly intracytoplasmic sperm injection (ICSI), it became clear that these
      parameters are insufficient for the identification of the most suitable
      spermatozoon for fertilization. Conventional sperm preparation techniques,
      namely, swim-up, density gradient centrifugation and glass wool filtration, are
      not efficient enough to produce sperm populations free of DNA damage, because
      these techniques are not physiological and not modeled on the stringent sperm
      selection processes taking place in the female genital tract. These processes
      only allow one male germ cell out of tens of millions to fuse with the oocyte.
      Sites of sperm selection in the female genital tract are the cervix, uterus,
      uterotubal junction, oviduct, cumulus oophorus and the zona pellucida. Newer
      strategies of sperm preparation are founded on: (i) morphological assessment by
      means of 'motile sperm organelle morphological examination (MSOME)'; (ii)
      electrical charge; and (iii) molecular binding characteristics of the sperm cell.
      Whereas separation methods based on electrical charge take advantage of the
      sperm's adherence to a test tube surface or separate in an electrophoresis,
      molecular binding techniques use Annexin V or hyaluronic acid (HA) as substrates.
      Techniques in this category are magnet-activated cell sorting, Annexin V
      activated glass wool filtration, flow cytometry and picked spermatozoa for ICSI
      (PICSI) from HA-coated dishes and HA-containing media. Future developments may
      include Raman microspectrometry, confocal light absorption and scattering
      spectroscopic microscopy and polarization microscopy.

PMID- 22138909
TI  - Virtual issue on polymorphism.

PMID- 22138908
TI  - Management problems of intramedullary holocord abscess: an illustration in a
      pediatric case.

PMID- 22138910
TI  - Li(12)Cu(12.60)Al(14.37): a new ternary derivative of the binary Laves phases.
AB  - New ternary dodecalithium dodecacopper tetradecaaluminium,
      Li(12)Cu(12.60)Al(14.37) (trigonal, R 3m, hR39), crystallizes as a new structure
      type and belongs to the structural family that derives from binary Laves phases.
      The Li atoms are enclosed in 15- and 16-vertex and the Al3 atom in 14-vertex
      pseudo-Frank-Kasper polyhedra. The polyhedra around the statistical mixtures of
      (Cu,Al)1 and (Al,Cu)2 are distorted icosahedra. The electronic structure was
      calculated by the TB-LMTO-ASA (tight-binding linear muffin-tin orbital atomic
      spheres approximation) method. The electron localization function, which
      indicates bond formation, is mostly located at the Al atoms. Thus, Al-Al bonding
      is much stronger than Li-Al or Cu-Al bonding. This indicates that, besides
      metallic bonding which is dominant in this compound, weak covalent Al-Al
      interactions also exist.

PMID- 22138911
TI  - An octanuclear iron(III) isobutyrate wheel.
AB  - The reaction of the MU(3)-oxido-centred trinuclear isobutyrate cluster
      [Fe(3)O(O(2)CCHMe(2))(6)(H(2)O)(3)](+) with an excess of phenol (PhOH) in
      chloroform produces a novel octanuclear Fe(III) cluster, cyclo-tetra-MU(2)
      hydroxido-dodeca-MU(2)-isobutyrato-kappa(24)O:O'-octa-MU(2)-phenolato
      kappa(16)O:O'-octairon(III) phenol hexasolvate monohydrate,
      [Fe(8)(C(4)H(7)O(2))(12)(C(6)H(5)O)(8)(OH)(4)].6C(6)H(5)OH.H(2)O. The neutral
      cluster is located about a centre of inversion and consists of a planar ring of
      eight Fe(III) centres with two types of bridges between adjacent Fe atoms: each
      Fe atom is bridged to one of its neighbours by a MU-hydroxide and two 1,3
      bridging carboxylates, or by two phenolate and one 1,3-bridging isobutyrate
      ligand. The cavity within the {Fe(8)} wheel is occupied by a disordered water
      molecule. Intermolecular O-H...O hydrogen bonds and C-H...pi interactions connect
      the clusters and the phenol solvent molecules to form a three-dimensional
      network.

PMID- 22138912
TI  - The three-dimensional intermolecular network formed via water molecules in trans
      bis(nitrito-kappaN)tetrakis(pyridine-kappaN)ruthenium(II) dihydrate.
AB  - The molecular geometry of the tetragonal crystal structure of the title compound,
      [Ru(NO(2))(2)(C(5)H(5)N)(4)].2H(2)O, differs from that previously determined by
      powder diffraction [Schaniel et al. (2010). Phys. Chem. Chem. Phys. 12, 6171
      6178]. In the [Ru(NO(2))(C(5)H(5)N)(4)] molecule, the Ru atom lies at the
      intersection of three twofold axes (Wyckoff position 8b). It is coordinated by
      four N atoms of the pyridine rings, as well as by two N atoms of N-nitrite
      groups. The last two N atoms are located on a twofold axis (Wyckoff position
      16f). The O atoms of the water molecules are situated on a twofold axis (Wyckoff
      position 16e). Short intermolecular contacts are observed in the crystal
      structure, viz. N-O...OW and N-O...H-OW contacts between nitrite and water, and
      weak C-H...OW hydrogen bonds between pyridine and water. Thus, the intercalated
      water molecules act as bridges connecting the trans-[Ru(NO(2))(2)(py)(4)]
      molecules into a three-dimensional network.

PMID- 22138913
TI  - New organic-inorganic frameworks incorporating iso- and heteropolymolybdate units
      and a 3,3',5,5'-tetramethyl-4,4'-bi-1H-pyrazole-2,2'-diium multiple hydrogen-bond
      donor.
AB  - Poly[bis(3,3',5,5'-tetramethyl-4,4'-bi-1H-pyrazole-2,2'-diium) gamma
      octamolybdate(VI) dihydrate], {(C(10)H(16)N(4))(2)[Mo(8)O(26)].2H(2)O}(n), (I),
      and bis(3,3',5,5'-tetramethyl-4,4'-bi-1H-pyrazole-2,2'-diium) alpha
      dodecamolybdo(VI)silicate tetrahydrate,
      (C(10)H(16)N(4))(2)[SiMo(12)O(40)].4H(2)O, (II), display intense hydrogen bonding
      between the cationic pyrazolium species and the metal oxide anions. In (I), the
      asymmetric unit contains half a centrosymmetric gamma-type [Mo(8)O(26)](4-)
      anion, which produces a one-dimensional polymeric chain by corner-sharing, one
      cation and one water molecule. Three-centre bonding with 3,3',5,5'-tetramethyl
      4,4'-bi-1H-pyrazole-2,2'-diium, denoted [H(2)Me(4)bpz](2+) [N...O = 2.770 (4)
      3.146 (4) A], generates two-dimensional layers that are further linked by
      hydrogen bonds involving water molecules [O...O = 2.902 (4) and 3.010 (4) A]. In
      (II), each of the four independent [H(2)Me(4)bpz](2+) cations lies across a
      twofold axis. They link layers of [SiMo(12)O(40)](4-) anions into a three
      dimensional framework, and the preferred sites for pyrazolium/anion hydrogen
      bonding are the terminal oxide atoms [N...O = 2.866 (6)-2.999 (6) A], while
      anion/aqua interactions occur preferentially via MU(2)-O sites [O...O = 2.910 (6)
      3.151 (6) A].

PMID- 22138914
TI  - A novel heterometallic dinuclear compound: rac-pentaaqua-1kappa5O-(MU-2
      sulfidoacetato-1:2kappa3O:O',S)bis(2-sulfidoacetato
      2kappa2O,S)manganese(II)tin(IV).
AB  - The title racemic heterometallic dinuclear compound,
      [MnSn(C(2)H(2)O(2)S)(3)(H(2)O)(5)], (I), contains one main group Sn(IV) metal
      centre and one transition metal Mn(II) centre, and, by design, links the Mn(II)
      centre to the building unit of the (Delta/Lambda) [SnL(3)](2-) complex anion (L
      is the 2-sulfidoacetate dianion). In this cluster, the Sn(IV) centre of the
      (Delta/Lambda) [SnL(3)](2-) unit is coordinated by three O atoms and three S
      atoms from three L ligands to form an [SnO(3)S(3)] octahedral coordination
      environment. The Mn(II) centre is in an [MnO(6)] octahedral coordination
      environment, with five O atoms from five water molecules and the sixth from the
      MU(2)-L ligand of the (Delta/Lambda) [SnL(3)](2-) unit. Between adjacent
      dinuclear molecules, there are many hydrogen-bond interactions of O-H...O, O
      H...S, C-H...O and C-H...S types. Of these, eight pairs of O-H...O hydrogen bonds
      fuse all the dinuclear molecules into two-dimensional supramolecular sheets along
      the bc plane. Adjacent supramolecular sheets are further connected through O
      H...S hydrogen bonds to give a three-dimensional supramolecular network.

PMID- 22138915
TI  - Poly[bis(2,2'-bipyridine-kappa(2)N,N')bis(MU(6)-2,4,6-trimethylbenzene-1,3,5
      tricarboxylato)tricadmium(II)], a two-dimensional 'Kagome dual' (kgd) sheet
      structure.
AB  - The title metal-organic framework,
      [Cd(3)(C(12)H(9)O(6))(2)(C(10)H(8)N(2))(2)](n), has been synthesized by a
      solvothermal reaction. The Cd(II) ions are located in CdO(4)N(2) and CdO(6) six
      coordinated environments, with the latter Cd(II) ion lying on an inversion
      centre. The 2,4,6-trimethylbenzene-1,3,5-tricarboxylate ligand (TMBTC) connects
      the Cd(II) ions to form a two-dimensional sheet incorporating hourglass-like
      [Cd(3)(COO)(6)] secondary building units (SBUs). Topologically, taking the TMBTC
      ligand and the [Cd(3)(COO)(6)] SBU as 3- and 6-connected nodes, respectively, the
      overall two-dimensional sheet can be simplified to a rare (3,6)-connected 2-nodal
      kgd (Kagome dual) net with a short Schlafli vertex notation of
      {4(3)}(2){4(6).6(6).8(3)}, which further stacks into a three-dimensional
      supramolecular framework through pi-pi stacking interactions.

PMID- 22138916
TI  - [eta6-1-Chloro-2-(pyrrolidin-1-yl)benzene](eta5-cyclopentadienyl)iron(II)
      hexafluoridophosphate and (eta5-cyclopentadienyl){2-[eta6-2-(pyrrolidin-1
      yl)phenyl]phenol}iron(II) hexafluoridophosphate.
AB  - In the complex salt [eta(6)-1-chloro-2-(pyrrolidin-1-yl)benzene](eta(5)
      cyclopentadienyl)iron(II) hexafluoridophosphate,
      [Fe(C(5)H(5))(C(10)H(12)ClN)]PF(6), (I), the complexed cyclopentadienyl and
      benzene rings are almost parallel, with a dihedral angle between their planes of
      2.3 (3) degrees . In a related complex salt, (eta(5)-cyclopentadienyl){2-[eta(6)
      2-(pyrrolidin-1-yl)phenyl]phenol}iron(II) hexafluoridophosphate,
      [Fe(C(5)H(5))(C(16)H(17)NO)]PF(6), (II), the analogous angle is 5.4 (1) degrees .
      In both complexes, the aromatic C atom bound to the pyrrolidine N atom is located
      out of the plane defined by the remaining five ring C atoms. The dihedral angles
      between the plane of these five ring atoms and a plane defined by the N-bound
      aromatic C atom and two neighboring C atoms are 9.7 (8) and 5.6 (2) degrees  for
      (I) and (II), respectively.

PMID- 22138917
TI  - Poly[tetrakis(n-propylammonium) [octa-MU-chlorido-dichloridotrinickelate(II)]]: a
      hybrid organic-inorganic layer compound in the Cs4Mg3F10 structure type.
AB  - The title compound, {(C(3)H(10)N)(4)[Ni(3)Cl(10)]}(n), contains zigzag layers of
      tri-MU-chlorido-bridged linear 2/m-symmetric Ni(3)Cl(12) segments, linked by mono
      MU-chlorido quasi-linear bridges to two other segments at each end. These
      inorganic layers are interleaved with interdigitated bilayers of mirror-symmetric
      n-propylammonium cations, the ammonium head groups of which are directed into the
      inorganic layers to form multiple N-H...Cl hydrogen bonds, while the propyl tail
      groups pack together in a tongue-and-groove manner in the center of the bilayer.
      The propyl groups are ordered at 100 K but disordered with opposite conformations
      on the mirror plane at 240 K.

PMID- 22138918
TI  - 2-Sulfoethylammonium hexafluoridoantimonate.
AB  - The title salt, (C(2)H(8)NO(3)S)[SbF(6)], which contains the protonated form of
      taurine (2-aminoethanesulfonic acid), was synthesized in anhydrous hydrofluoric
      acid and recrystallized as colourless block-shaped crystals from liquid SO(2). In
      the solid state, a three-dimensional network is observed. This is formed by intra
      and intermolecular N-H...O, N-H...F and O-H...F hydrogen bonds.

PMID- 22138919
TI  - A pi-stacked chain of hydrogen-bonded dimers in 3-tert-butyl-1-(4-chlorophenyl)-4
      phenylindeno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-one and a pi-stacked sheet of
      hydrogen-bonded chains in 3-tert-butyl-1-(4-chlorophenyl)-4-(4
      methoxyphenyl)indeno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-one.
AB  - In 3-tert-butyl-1-(4-chlorophenyl)-4-phenylindeno[1,2-b]pyrazolo[4,3-e]pyridin
      5(1H)-one, C(29)H(22)ClN(3)O, (I), inversion-related pairs of molecules are
      linked by C-H...O hydrogen bonds to form R(2)(2)(18) dimers, which are themselves
      linked into a chain by a pi-pi stacking interaction between inversion-related
      pairs of molecules. In 3-tert-butyl-1-(4-chlorophenyl)-4-(4
      methoxyphenyl)indeno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-one,
      C(30)H(24)ClN(3)O(2), (II), which crystallizes in the space group P-1, with Z' =
      2 and with different orientations for the methoxy groups in the two independent
      molecules, a combination of C-H...O and C-H...pi(arene) hydrogen bonds links the
      molecules into chains of rings, which are further linked into sheets by a pi-pi
      stacking interaction.

PMID- 22138920
TI  - Two tautomeric polymorphs of 2,6-dichloropurine.
AB  - Two polymorphs of 2,6-dichloropurine, C(5)H(2)Cl(2)N(4), have been crystallized
      and identified as the 9H- and 7H-tautomers. Despite differences in the space
      group and number of symmetry-independent molecules, they exhibit similar hydrogen
      bonding motifs. Both crystal structures are stabilized by intermolecular N-H...N
      interactions that link adjacent molecules into linear chains, and by some
      nonbonding contacts of the C-Cl...pi type and by pi-pi stacking interactions,
      giving rise to a crossed two-dimensional herringbone packing motif. The main
      structural difference between the two polymorphs is the different role of the
      molecules in the pi-pi stacking interactions.

PMID- 22138921
TI  - Sulfapyridine (polymorph III), sulfapyridine dioxane solvate, sulfapyridine
      tetrahydrofuran solvate and sulfapyridine piperidine solvate, all at 173 K.
AB  - The X-ray crystal structures of solvates of sulfapyridine have been determined to
      be conformational polymorphs. 4-Amino-N-(1,2-dihydropyridin-2
      ylidene)benzenesulfonamide (polymorph III), C(11)H(11)N(3)O(2)S, (1), 4-amino-N
      (1,2-dihydropyridin-2-ylidene)benzenesulfonamide 1,3-dioxane monosolvate,
      C(11)H(11)N(3)O(2)S.C(4)H(8)O(2), (2), and 4-amino-N-(1,2-dihydropyridin-2
      ylidene)benzenesulfonamide tetrahydrofuran monosolvate,
      C(11)H(11)N(3)O(2)S.C(4)H(8)O, (3), crystallized as the imide form, while
      piperidin-1-ium 4-amino-N-(pyridin-2-yl)benzenesulfonamidate,
      C(5)H(12)N(+).C(11)H(10)N(3)O(2)S(-), (4), crystallized as the piperidinium salt.
      The tetrahydrofuran and dioxane solvent molecules in their respective structures
      were disordered and were refined using a disorder model. Three-dimensional
      hydrogen-bonding networks exist in all structures between at least one sulfone O
      atom and the aniline N atom.

PMID- 22138922
TI  - Two polymorphs of N1,N4-bis(5-hydroxypenta-1,3-diynyl)-N1,N4-diphenylbenzene-1,4
      diamine.
AB  - The title compound, C(28)H(20)N(2)O(2), forms two conformational polymorphs, (I)
      and (II), where the molecular structures are similar except for the orientation
      of the two hydroxy groups. In (I), which was obtained by slow evaporation from
      chloroform, the two hydroxy groups have an anti conformation. The molecules form
      a sheet structure within the ac plane, where the hydroxy groups form zigzag
      hydrogen bonds. In (II), which was obtained by slow evaporation from
      acetonitrile, the two hydroxy groups have a syn conformation. The molecules form
      a double-sheet structure within the ab plane, where the hydroxy groups form 4
      helix hydrogen bonds.

PMID- 22138923
TI  - Polymorphs of anhydrous theophylline: stable form IV consists of dimer pairs and
      metastable form I consists of hydrogen-bonded chains.
AB  - The structure of a previously unreported polymorph of anhydrous theophylline (1,3
      dimethyl-3,7-dihydro-1H-purine-2,6-dione), C(7)H(8)N(4)O(2), has been determined
      at 100 K and shown to have monoclinic symmetry with Z' = 2. The structure is
      named form IV and experimental observation indicates that this is the stable form
      of the material. The molecular packing consists of discrete hydrogen-bonded
      dimers similar to that observed in the monohydrate structure. The structure of
      form I has also been determined and consists of hydrogen-bonded chains.

PMID- 22138924
TI  - Hydrogen-bonded structures of the 1:1 and 1:2 compounds of chloranilic acid with
      pyrrolidin-2-one and piperidin-2-one.
AB  - In the four compounds of chloranilic acid (2,5-dichloro-3,6-dihydroxycyclohexa
      2,5-diene-1,4-dione) with pyrrolidin-2-one and piperidin-2-one, namely,
      chloranilic acid-pyrrolidin-2-one (1/1), C(6)H(2)Cl(2)O(4).C(4)H(7)NO, (I),
      chloranilic acid-pyrrolidin-2-one (1/2), C(6)H(2)Cl(2)O(4).2C(4)H(7)NO, (II),
      chloranilic acid-piperidin-2-one (1/1), C(6)H(2)Cl(2)O(4).C(5)H(9)NO, (III), and
      chloranilic acid-piperidin-2-one (1/2), C(6)H(2)Cl(2)O(4).2C(5)H(9)NO, (IV), the
      shortest interactions between the two components are O-H...O hydrogen bonds,
      which act as the primary intermolecular interaction in the crystal structures. In
      (II), (III) and (IV), the chloranilic acid molecules lie about inversion centres.
      For (III), this necessitates the presence of two independent acid molecules. In
      (I), there are two formula units in the asymmetric unit. The O...O distances are
      2.4728 (11) and 2.4978 (11) A in (I), 2.5845 (11) A in (II), 2.6223 (11) and
      2.5909 (10) A in (III), and 2.4484 (10) A in (IV). In the hydrogen bond of (IV),
      the H atom is disordered over two positions with site occupancies of 0.44 (3) and
      0.56 (3). This indicates that proton transfer between the acid and base has
      partly taken place to form ion pairs. In (I) and (II), N-H...O hydrogen bonds,
      the secondary intermolecular interactions, connect the pyrrolidin-2-one molecules
      into a dimer, while in (III) and (IV) these hydrogen bonds link the acid and base
      to afford three- and two-dimensional hydrogen-bonded networks, respectively.

PMID- 22138925
TI  - The disordered molecular structure of (3aRS,7aRS)-1,3-dinitrosooctahydro-1H
      benzimidazole.
AB  - The title compound, C(7)H(12)N(4)O(2), was obtained by nitrosation of the aminal
      cage (2R,7R,11S,16S)-1,8,10,17
      tetraazapentacyclo[8.8.1.1(8,17).0(2,7).0(11,16)]icosane. The crystal structure
      is a racemic mixture of RR and SS enantiomers. The asymmetric unit contains two
      crystallographically independent half-molecules, one having two partially
      occupied conformers with refined occupancy factors of 0.747 (3) and 0.253 (3).
      The molecules sit across twofold axes. The unique molecules each form chains
      parallel to [001], with molecules connected by intermolecular C-H...O hydrogen
      bonds. The bonding between adjacent chains is weak. The analysis of eight
      different crystals confirmed the presence of disordered and nondisordered
      molecules in the same structure as a regular feature.

PMID- 22138926
TI  - 2,5-Diaryl-1,3,4-selenadiazoles prepared from Woollins' reagent.
AB  - Two polymorphs of 2,5-diphenyl-1,3,4-selenadiazole, C(14)H(10)N(2)Se, denoted
      (Ia) and (Ib), and a new polymorph of 2,5-bis(thiophen-2-yl)-1,3,4-selenadiazole,
      C(10)H(6)N(2)S(2)Se, (IIb), form on crystallization of the compounds, prepared
      using Woollins' reagent (2,4-diphenyl-1,3-diselenadiphosphetane 2,4-diselenide).
      These compounds, along with 2-(4-chlorophenyl)-5-phenyl-1,3,4-selenadiazole,
      C(14)H(9)ClN(2)Se, (III), and 2-(furan-2-yl)-5-(p-tolyl)-1,3,4-selenadiazole,
      C(13)H(10)N(2)OSe, (IV), show similar intermolecular interactions, with pi-pi
      stacking, C-H...pi interactions and weak hydrogen bonds typically giving rise to
      molecular chains. However, the combination of interactions differs in each case,
      giving rise to different packing arrangements. In polymorph (Ib), the molecule
      lies across a crystallographic twofold rotation axis, and (IV) has two
      independent molecules in the asymmetric unit.

PMID- 22138927
TI  - A meta-analysis of D1 versus D2 lymph node dissection.
AB  - BACKGROUND: Surgery is the only curative treatment for patients with gastric
      cancer. However, the extent of lymph node dissection is still debated. Therefore,
      with the publication of newer trial results, we conducted an updated meta
      analysis of D1 versus D2 randomized controlled trials comparing outcomes.
      METHODS: Systematic searches were conducted using Medline, Embase, and the
      Cochrane Central Register of Controlled Trials from January 1, 1985, to December
      31, 2010. Meta-analyses were performed using RevMan v5 software. Both short- and
      long-term outcomes were analyzed. Subgroup analyses of T stage and
      spleen/pancreas resection versus preservation were performed. RESULTS: Outcomes
      of 5 randomized trials involving 1642 patients (845 D1, 797 D2) enrolled from
      1982 to 2005 were included. Despite the addition of the more recent trials,
      overall hospital mortality and reoperation rates were still higher in D2 cases.
      Subgroup analysis of recent trials and spleen/pancreas preservation revealed no
      significant difference in hospital mortality between groups. Five-year overall
      survival was similar between D1 versus D2 trials. Sub-analysis by tumor depth and
      spleen/pancreas preservation detected trends for improved survival with D2
      lymphadenectomy in T3/T4 patients and those with spleen/pancreas preservation.
      CONCLUSION: Earlier trials show that D2 dissections have higher operative
      mortality, while recent trials have similar rates. A trend of improved survival
      exists among D2 patients who did not undergo resection of the spleen or pancreas,
      as well as for patients with T3/T4 cancers.

PMID- 22138928
TI  - Systematic review of the predictors of positive margins in gastric cancer surgery
      and the effect on survival.
AB  - BACKGROUND: Complete resection is the only definitive treatment available for
      gastric cancer. Factors associated with positive margins and their survival
      effects have been the subject of many studies, but the appropriate management for
      these patients is still debated. The objective of this review is to examine
      positive margins after gastric cancer resections by exploring predictive factors,
      impact on survival, and optimal strategies for re-resection. METHODS: A
      systematic electronic literature search was conducted using Medline and EMBASE
      from January 1, 1998, to December 31, 2009. Studies on gastric or
      gastroesophageal junction adenocarcinoma that either investigated the predictors
      for positive margin or employed multivariate methods to analyze the survival
      effects of positive margins were selected. RESULTS: Twenty-two studies
      incorporating 19355 patients were included in this review. Positive margins were
      associated with larger tumor size, deeper wall penetration, more extensive
      gastric involvement, greater nodal involvement, higher stage, diffuse histology,
      higher Borrmann type, lymphatic vessel involvement, and total gastrectomy.
      Patient survival was independently associated with margin status, and this
      survival effect was more prominent in early cancers in most studies that
      performed subgroup analyses. CONCLUSIONS: The probability of acquiring positive
      margins is highly dependent on the biology and the extent of the tumor. There is
      a significant negative effect on survival, which is more prominent in cancers at
      early stages, making re-resection or a second operation important. Patients with
      more advanced disease can be offered more extensive surgery to remove disease,
      but this should be balanced against the risks of more extensive resections.

PMID- 22138929
TI  - Screening and minimally invasive treatment for gastric cancer are important
      challenges in elderly patients.

PMID- 22138930
TI  - Tossing and turning--insomnia in relation to occupational stress, rumination,
      fatigue, and well-being.
AB  - OBJECTIVES: This study of a large and heterogeneous sample of 5210 daytime
      employees was designed to shed more light on the work effort-recovery mechanism
      by examining the cross-sectional relations between subjective sleep quality and
      (i) psychosocial work characteristics, (ii) work-related rumination, (iii)
      fatigue after work, and (iv) affective well-being at work and work pleasure.
      METHODS: We used the Dutch Questionnaire on the Experience and Evaluation of Work
      and created three sleep quality groups (low, low-to-intermediate, and high
      quality). Group differences were studied through analysis of variance (ANOVA). To
      examine the relations among the study variables in more detail, we also conducted
      four sets of stepwise regression analyses. In all the analyses, we corrected for
      age, level of education, and gender. RESULTS: A series of (M)ANOVA provided
      strong evidence for a relation between sleep quality and adverse work
      characteristics and work-related rumination. Furthermore, poor sleepers reported
      higher levels of fatigue after work, and poor sleep quality was related to both
      lower affective well-being during work and work pleasure. Regression analyses
      revealed that sleep quality was the strongest statistical predictor of after-work
      fatigue and affective well-being at work, and high levels of work rumination
      constituted the strongest statistical predictor of sleep complaints. CONCLUSIONS:
      As this study showed strong relations between sleep quality, occupational stress,
      fatigue, perseverative cognitions, and work motivation, it supports effort
      recovery theory. Interventions should aim to prevent a disbalance between effort
      and recovery.

PMID- 22138931
TI  - Complex factors and behaviors in the gambling population of Italy.
AB  - Gambling has seen significant growth globally, and particularly in Italy: it has
      rapidly evolved from a simple recreational activity to represent 4% of Italian
      GDP in 2010.A sample of 4.494 gamblers was drawn from IPSAD-Italia((r))2007-2008
      (Italian Population Survey on Alcohol and Drugs) in order to examine different
      gambling patterns (assessed using the Canadian Problem Gambling Index Short form
      scale).Separate analysis was performed on young adults, age 15-24 (n = 1,241;
      male 56.2%), and adults, age 25-64 (n = 3,253; male 53.8%): compared with adults,
      Italian youth, although they gambled less (35.7% vs. 45.3%), appeared to have
      higher prevalence of low risk gambling (6.9% vs. 5.8%) and moderate risk or
      problem gambling (2.3% vs. 2.2%). Males are more likely to be moderate-risk or
      problem gamblers. Those with only a primary education are more likely to be
      moderate-risk or problem gamblers (young adults: RRR = 5.22; adults: RRR = 3.23)
      than those with a university education, just like those youth who use
      depressants, but only among younger (RRR = 3.38).A fundamental issue, "do not
      disapprove of gambling", seems to relate to problematic gambling: a specific
      Italian legislation, the Abruzzi Decree Law, could have influenced the perception
      that gambling may contribute positively to provide additional funds to the
      government for social good as well as to add needed jobs. Regardless of such
      potential social benefits, gambling is a social epidemic and if this association
      should be confirmed by more focused studies, policy makers should evaluate ways
      to affect this perception as soon as possible.

PMID- 22138933
TI  - The impact of the quality of colon preparation on follow-up colonoscopy
      recommendations.
AB  - OBJECTIVES: Published guidelines for timing of follow-up colonoscopy assume that
      the entire colon mucosa is visualized and provide no guidance in the case of poor
      preparations. We aimed to determine how preparation quality during screening
      colonoscopy affects gastroenterologists' recommendations on the timing of follow
      up colonoscopy. METHODS: Gastroenterologists were shown representative images of
      four colonoscopies with differing colon-preparation quality. For each set of
      images they were asked to recommend when a hypothetical patient with no polyps or
      malignancy on screening examination should return for a subsequent colonoscopy.
      For the same patient, gastroenterologists were asked to give recommendations
      based on a preparation-quality grading scale. RESULTS: The survey was completed
      by 239 gastroenterologists. Nearly all recommended 10-year follow-up colonoscopy
      for the best-appearing preparation. For the three imperfect preparations there
      was considerable variability in recommendations; follow-up timing ranged from 1-2
      days to 10 years for identical preparations. Similar variability was seen in
      recommendations based on a preparation-quality grading scale. Endoscopists
      generally recommended progressively shorter-interval follow-up as colon
      preparation worsened, with median recommended follow-up of 10, 5, 1, and 0.25
      years for the four sets of images. No association was seen between personal
      demographics or practice characteristics and follow-up recommendations.
      CONCLUSIONS: When colon preparation is imperfect, gastroenterologists provide
      highly variable recommendations regarding timing of follow-up colonoscopy.

PMID- 22138935
TI  - Image of the month: circumferential ulceration just proximal to an
      esophagogastric anastomosis.

PMID- 22138934
TI  - Potential use of telemedicine to provide outpatient care for inflammatory bowel
      disease.
AB  - OBJECTIVES: Patients with inflammatory bowel disease (IBD) often experience
      barriers to subspecialty access. We applied telemedicine, using a new
      computerized system called Collaborative Imaging, to resolve these barriers. We
      studied patients' experience and satisfaction, and clinic throughput. METHODS: We
      performed a prospective randomized controlled pilot study at a Veterans Affairs
      hospital, assigning patients into two groups: telemedicine encounter, with the
      IBD specialist remotely located, and standard encounter. We assessed patient
      experience and measured differences in satisfaction as well as clinic metrics
      such as appointment duration, wait time, and throughput. RESULTS: We enrolled 34
      patients with Crohn's disease and ulcerative colitis who underwent 57 encounters
      in 9 months. Patients were mostly Caucasian men, with a mean age of 61 years. The
      two groups similarly rated as excellent their clinic experience and the major
      clinical satisfaction indices of attention to patient concerns, bedside manner,
      and perceived skill level of the doctor. The total clinic duration, wait time,
      and median number of patients per clinic were also similar. The fellow and
      subspecialist highly rated the technical and informational quality of the
      telemedicine sessions. CONCLUSIONS: IBD outpatient service may be delivered via a
      novel telemedicine system. In this pilot study, we observed a high level of
      patient satisfaction similar to that achieved with a direct clinical encounter.

PMID- 22138940
TI  - Editorial: staging liver fibrosis in hepatitis C: a challenge for this decade.
AB  - The limitations of and the invasive nature of liver biopsy has spurred extensive
      interest in the development of non-invasive tests to measure liver fibrosis in
      patients with chronic hepatitis C. Clinically applicable non-invasive tests,
      including radiological studies, elastography, and serum markers, all of which
      perform extremely well in excluding significant disease and diagnosing cirrhosis.
      FibroScan and acoustic radiation force impulse elastography are two elastography
      based tests that show promise. In this new era of increased cure rates with newly
      Food and Drug Administration-approved drugs and the availability of multiple non
      invasive tests of liver fibrosis, we anticipate a decreasing need for liver
      biopsies in the management of chronic hepatitis C.

PMID- 22138941
TI  - Editorial: bugs and drugs: insights into the pathogenesis of inflammatory bowel
      disease.
AB  - The dysbiosis hypothesis posits that perturbations in the gut microbiome may
      contribute to the development of inflammatory bowel disease (IBD). A recent
      Canadian population-based study has shown an association between new-onset IBD
      and antibiotic use in the 2-5 years preceding diagnosis. Though these findings do
      not establish a causal relationship, it supports the role of dysbiosis in the
      pathogenesis of IBD. Furthermore, the study reinforces the importance of the
      judicious use of antibiotics.

PMID- 22138942
TI  - Editorial: endoscopic stent placement as a bridge to surgery in malignant
      colorectal obstruction: a balance between study validity and real-world
      applicability.
AB  - The premise of self-expandable metal stent placement to restore luminal
      continuity in patients with acute left-sided malignant colonic obstruction is
      intuitively logical. However, the available body of literature addressing their
      benefit in this setting is contradictory. We sought to briefly critique the
      available literature and put the findings of Jimenez-Perez et al. published in
      this current issue of the American Journal of Gastroenterology in perspective.

PMID- 22138943
TI  - Editorial: drug-induced acute pancreatitis: uncommon or commonplace?
AB  - Many drugs have been implicated as causing acute pancreatitis (AP), mainly based
      on the recurrence of pancreatitis following rechallenge with a drug that the
      patient had been taking at the time of an initial episode of AP. However,
      estimates of the relative frequency with which drugs cause AP vary widely. This
      is largely because many patients may be taking a number of drugs, may have co
      morbidities such as gallstone disease or hypertriglyceridemia, or may be
      consuming large amounts of alcohol, making it difficult to determine what
      actually is the primary cause of an episode of AP. Large, rigorously designed
      epidemdiological studies are needed to better define the frequency with which the
      drugs in general cause AP and the specific risk of pancreatitis associated with
      any individual drug.

PMID- 22138944
TI  - Re: opioid-induced constipation: challenges and therapeutic opportunities.

PMID- 22138947
TI  - Are non-celiac disease gluten-intolerant patients innate immunity responders to
      gluten?

PMID- 22138948
TI  - Nail changes: unusual presentation of celiac disease.

PMID- 22138949
TI  - Tragic death of Ismar Boas: the father of gastroenterology.

PMID- 22138950
TI  - Low dose of bevacizumab is safe and effective in preventing bleeding episodes in
      hereditary hemorrhagic telangiectasia.

PMID- 22138951
TI  - Magnificent gallbladder enlargement due to huge duodenal adenocarcinoma.

PMID- 22138955
TI  - Dithienylcyclopentene-functionalised subphthalocyaninatoboron complexes:
      photochromism, luminescence modulation and formation of self-assembled monolayers
      on gold.
AB  - Subphthalocyaninatoboron (SubPc) complexes bearing six peripheral n-dodecylthio
      substituents and an apical photochromic dithienylperfluorocyclopentene unit were
      prepared. The photoinduced isomerisation of the apical substituent from the open
      to the ring-closed form significantly influences the photoluminescence of the
      covalently attached SubPc unit, which is more efficiently quenched by the ring
      closed form. Films on gold were fabricated from these multifunctional conjugates
      and characterised by near-edge X-ray absorption fine structure (NEXAFS) and X-ray
      photoelectron spectroscopy (XPS). The results are in accord with the formation of
      self-assembled monolayers based on dome-shaped SubPc-based anchor groups. Their
      chemisorption is primarily due to the peripheral n-dodecylthio substituents,
      giving rise to covalently attached thiolate as well as coordinatively bound
      thioether units, whose alkyl chains are in an almost parallel orientation to the
      surface.

PMID- 22138956
TI  - Sputnik and Mavirus: more than just satellite viruses.

PMID- 22138957
TI  - Immune evasion: Size does matter.

PMID- 22138960
TI  - The battle of the SNPs.

PMID- 22138961
TI  - Risk of bleeding after percutaneous endoscopic gastrostomy (PEG).
AB  - BACKGROUND: Patients who undergo percutaneous endoscopic gastrostomy (PEG)
      placement are often on anticoagulation and/or antiplatelet therapy with a
      potential thromboembolic risk if these medications are discontinued. Data on the
      safety of peri-procedural use of these drugs is limited. AIMS: To assess the risk
      and to identify any predictive factors for post-PEG bleeding, and to determine if
      clopidogrel increases the risk of bleeding following PEG. METHODS: A
      retrospective chart audit was conducted from January 1, 2002 to June 30, 2011.
      RESULTS: A total of 1,541 patients underwent PEG placement during this period.
      Gastrointestinal bleeding after PEG placement occurred in 51 cases (3.3%) and
      bleeding directly attributed to PEG was noted in six patients (0.4%).
      Multivariate logistic regression analysis of variables (age, gender, length of
      hospitalization, indication for PEG, antiplatelet or anticoagulant medications)
      showed that heparin infusion (P = 0.018) and length of hospitalization (P =
      0.029) were statistically significant predictors of bleeding. The mean period for
      cessation and resumption of clopidogrel with PEG placement were 2.2 and 1.3 days,
      respectively. CONCLUSION: Although PEG is classified as a high-risk endoscopic
      procedure, bleeding with PEG placement was rare, even with use of anticoagulation
      and antiplatelet medications. In selected patients on heparin infusion undergoing
      PEG, delaying the procedure, alternative use of low-molecular-weight heparin or
      close monitoring and frequent assessments should be considered. Clopidogrel did
      not contribute to an increase in bleeding risk, despite being held for a much
      shorter peri-procedural period as recommended by expert consensus.

PMID- 22138959
TI  - Conventional and unconventional mechanisms for capping viral mRNA.
AB  - In the eukaryotic cell, capping of mRNA 5' ends is an essential structural
      modification that allows efficient mRNA translation, directs pre-mRNA splicing
      and mRNA export from the nucleus, limits mRNA degradation by cellular 5'-3'
      exonucleases and allows recognition of foreign RNAs (including viral transcripts)
      as 'non-self'. However, viruses have evolved mechanisms to protect their RNA 5'
      ends with either a covalently attached peptide or a cap moiety (7-methyl-Gppp, in
      which p is a phosphate group) that is indistinguishable from cellular mRNA cap
      structures. Viral RNA caps can be stolen from cellular mRNAs or synthesized using
      either a host- or virus-encoded capping apparatus, and these capping assemblies
      exhibit a wide diversity in organization, structure and mechanism. Here, we
      review the strategies used by viruses of eukaryotic cells to produce functional
      mRNA 5'-caps and escape innate immunity.

PMID- 22138962
TI  - Relative contributions of afferent vagal fibers to resistance to diet-induced
      obesity.
AB  - BACKGROUND: We previously demonstrated vagal neural pathways, specifically
      subdiaphragmatic afferent fibers, regulate expression of the intestinal sodium
      glucose cotransporter SGLT1, the intestinal transporter responsible for
      absorption of dietary glucose. We hypothesized targeting this pathway could be a
      novel therapy for obesity. We therefore tested the impact of disrupting vagal
      signaling by total vagotomy or selective vagal de-afferentation on weight gain
      and fat content in diet-induced obese rats. METHODS: Male Sprague-Dawley rats (n
      = 5-8) underwent truncal vagotomy, selective vagal de-afferentation with
      capsaicin, or sham procedure. Animals were maintained for 11 months on a  high
      caloric Western diet. Abdominal visceral fat content was assessed by magnetic
      resonance imaging together with weight of fat pads at harvest. Glucose
      homeostasis was assessed by fasting blood glucose and HbA1C. Jejunal SGLT1 gene
      expression was assessed by qPCR and immunoblotting and function by glucose uptake
      in everted jejunal sleeves. RESULTS: At 11-months, vagotomized rats weighed 19%
      less (P = 0.003) and de-afferented rats 7% less (P = 0.19) than shams.
      Vagotomized and de-afferented animals had 52% (P < 0.0001) and 18% reduction (P =
      0.039) in visceral abdominal fat, respectively. There were no changes in blood
      glucose or glycemic indexes. SGLT1 mRNA, protein and function were unchanged
      across all cohorts at 11-months postoperatively. CONCLUSIONS: Truncal vagotomy
      led to significant reductions in both diet-induced weight gain and visceral
      abdominal fat deposition. Vagal de-afferentation led to a more modest, but
      clinically and statistically significant, reduction in visceral abdominal fat. As
      increased visceral abdominal fat is associated with excess morbidity and
      mortality, vagal de-afferentation may be a useful adjunct in bariatric surgery.

PMID- 22138963
TI  - Is KRAS mutation associated with interval colorectal cancers?
AB  - BACKGROUND: Colorectal cancers diagnosed in the interval after a complete
      colonoscopy may occur due to rapid tumor growth. Interval colorectal cancers are
      associated with microsatellite instability (MSI). AIMS: Our aim was to study the
      association of KRAS mutation with interval colorectal cancers and MSI. METHODS:
      We searched our institution's cancer registry for interval colorectal cancers,
      defined as colorectal cancers that developed within 5 years of a complete
      colonoscopy. These were frequency matched to patients with non-interval
      colorectal cancers. Archived cancer specimens were evaluated for KRAS mutations
      in codons 12 and 13 using sequencing, and MSI by sequencing microsatellite loci.
      Multivariable logistic regression was used to analyze the association between
      KRAS mutation status, MSI status and interval colorectal cancers. RESULTS: There
      were 63 interval and 131 non-interval colorectal cancers. KRAS mutation was
      present in 12.9% of interval cancers compared to 28.9% of non-interval cancers (P
      = 0.03). In multivariable logistic regression model, KRAS was inversely
      associated with interval cancers (OR 0.36; 95% CI 0.15-0.90). In Cox proportional
      hazards model, adjusting for age, tumor grade, TNM Stage and MSI status, we found
      no association between KRAS mutation and 5-year survival compared to cancers
      without KRAS mutation (HR 0.84; 95% CI 0.4-1.46; P = 0.5). CONCLUSIONS: KRAS
      mutation is inversely associated with interval cancers and with MSI, suggesting
      that it is a marker of the chromosomal instability pathway associated with slow
      tumor growth, and distinct from MSI rapidly growing cancers. Molecular
      characterization of colorectal cancers is helpful in determining underlying
      pathway and may determine therapy.

PMID- 22138964
TI  - Growth stimulation of iodide-oxidizing alpha-Proteobacteria in iodide-rich
      environments.
AB  - alpha-Proteobacteria that can oxidize iodide (I(-)) to molecular iodine (I(2))
      have only been isolated from iodide-rich natural and artificial environments,
      i.e., natural gas brine waters and seawaters supplemented with iodide,
      respectively. To understand the growth characteristics of such iodide-oxidizing
      bacteria (IOB) under iodide-rich environments, microcosms comprising natural
      seawater and 1 mM iodide were prepared, and the succession of microbial
      communities was monitored by culture-independent techniques. PCR-denaturing
      gradient gel electrophoresis and 16S rRNA gene sequence analysis showed that
      bacteria closely related with known IOB were predominant in the microcosms after
      several weeks of incubation. Quantitative PCR analysis targeting specific 16S
      rRNA gene regions of IOB showed that the relative abundance of IOB in the
      microcosms was 6-76% of the total bacterial population, whereas that in natural
      seawater was less than 1%. When 10(3) cells mL(-1) of IOB were inoculated into
      natural seawater supplemented with 0.1-1 mM iodide, significant growth (cell
      densities, 10(5)-10(6) cells mL(-1)) and I(2) production (6-32 MUM) were
      observed. Interestingly, similar growth stimulation occurred when 12-44 MUM of
      I(2) was added to seawater, instead of iodide. IOB were found to be more I(2)
      tolerant than the other heterotrophic bacteria in seawater. These results suggest
      that I(2) plays a key role in the growth stimulation of IOB in seawater. IOB
      could potentially attack other bacteria with I(2) to occupy their ecological
      niche in iodide-rich environments.

PMID- 22138965
TI  - Pediatric asthma caregiver's quality of life questionnaire is a useful tool for
      monitoring asthma in children.
AB  - PURPOSE: There is little agreement among researchers whether a caregiver's QOL
      can be used to detect changes in asthma severity in children. We assessed
      correlation between QOL in parents and QOL in children with asthma as well as
      clinical parameters of asthma. We determined whether changes in caregiver's QOL
      scores reflect changes in child's QOL and their asthma control. METHODS: This was
      a 9-week period cohort study. One hundred and ten primary caregivers with 110
      children were seen in the clinic at enrollment, at week #1, #5 and #9. At each
      visit, the parents completed the pediatric asthma caregiver's quality of life
      questionnaire (PACQLQ). RESULTS: One hundred and one children and 101 caregivers
      completed the study. We found a significant correlation between asthma diary
      score in children and QOL in parents (from r = -0.46 to r = -0.53). We also found
      significant positive correlation between PAQLQ and PACQLQ and significant
      association between changes in asthma control and PACQLQ score for both domains.
      We observed significant change in PACQLQ of caregivers whose children obtained
      asthma control. CONCLUSIONS: PACQLQ is a useful tool for monitoring asthma in
      children. The implementation of the PACQLQ would be helpful in involving parents
      in therapy of their children with asthma.

PMID- 22138967
TI  - Extracellular ATP promotes stomatal opening of Arabidopsis thaliana through
      heterotrimeric G protein alpha subunit and reactive oxygen species.
AB  - In recent years, adenosine tri-phosphate (ATP) has been reported to exist in
      apoplasts of plant cells as a signal molecule. Extracellular ATP (eATP) plays
      important roles in plant growth, development, and stress tolerance. Here,
      extracellular ATP was found to promote stomatal opening of Arabidopsis thaliana
      in light and darkness. ADP, GTP, and weakly hydrolyzable ATP analogs (ATPgammaS,
      Bz-ATP, and 2meATP) showed similar effects, whereas AMP and adenosine did not
      affect stomatal movement. Apyrase inhibited stomatal opening. ATP-promoted
      stomatal opening was blocked by an NADPH oxidase inhibitor (diphenylene iodonium)
      or deoxidizer (dithiothreitol), and was impaired in null mutant of NADPH oxidase
      (atrbohD/F). Added ATP triggered ROS generation in guard cells via NADPH oxidase.
      ATP also induced Ca(2+) influx and H(+) efflux in guard cells. In atrbohD/F, ATP
      induced ion flux was strongly suppressed. In null mutants of the heterotrimeric G
      protein alpha subunit, ATP-promoted stomatal opening, cytoplasmic ROS generation,
      Ca(2+) influx, and H(+) efflux were all suppressed. These results indicated that
      eATP-promoted stomatal opening possibly involves the heterotrimeric G protein,
      ROS, cytosolic Ca(2+), and plasma membrane H(+)-ATPase.

PMID- 22138966
TI  - Diagnostic delay, quality of life and patient satisfaction among women diagnosed
      with endometrial or ovarian cancer: a nationwide Danish study.
AB  - BACKGROUND: This study investigates the association between diagnostic delay
      (total delay), quality of life (QoL) and patient satisfaction, and the
      associations between QoL and patient satisfaction scores and survival for women
      diagnosed with ovarian or endometrial cancer. METHODS: A questionnaire survey was
      conducted among 723 women diagnosed with ovarian or endometrial cancer from 2006
      to 2007; 453 women were chosen to participate in the study. Data on total delay
      (number of weeks between first cancer symptom and initiation of treatment) were
      available from 353 women. RESULTS: Experiencing longer total delay was associated
      with reduced overall QoL and appetite loss among ovarian cancer patients, while
      longer total delay was associated with reduced overall QoL, reduced role and
      social functioning, and increased fatigue, insomnia and constipation among
      endometrial cancer patients. Likewise, longer total delay was associated with
      decreased patient satisfaction for both cancer types. For survival and QoL
      scores, worse scores for pain were statistically significantly associated with
      reduced survival for women diagnosed with ovarian cancer, while reduced overall
      QoL, physical, role and emotional functioning as well as increased nausea and
      vomiting, pain, dyspnoea and appetite loss were associated with reduced survival
      for women diagnosed with endometrial cancer. For survival and patient
      satisfaction, associations were not significant when adjusted for diagnosis, age,
      cancer stage and radicality of operation. CONCLUSIONS: We found that few QoL
      measures were associated with total delay and survival for ovarian cancer, while
      a number of associations were found between QoL, total delay and survival for
      endometrial cancer patients. This supports the hypothesis that long total delay
      may influence QoL and survival for some cancer patients. Reduced patient
      satisfaction with the diagnostic phase was also statistically significantly
      associated with long total delay, highlighting that total delay is an important
      component in patients' evaluation of the care they receive.

PMID- 22138968
TI  - On-off switches for secondary cell wall biosynthesis.
AB  - Secondary cell walls provide plants with rigidity and strength to support their
      body weight and ensure water and nutrient transport. They also provide textiles,
      timber, and potentially second-generation biofuels for human use. Genes
      responsible for synthesis of the different cell wall components, namely
      cellulose, hemicelluloses, and lignin, are coordinately expressed and under
      transcriptional regulation. In the past several years, cell wall-related NAC and
      MYB transcription factors have been intensively investigated in different species
      and shown to be master switches of secondary cell wall biosynthesis. Positive and
      negative regulators, which function upstream of NAC master switches, have also
      been identified in different plant tissues. Further elucidation of the regulatory
      mechanisms of cell wall synthesis will facilitate the engineering of plant
      feedstocks suitable for biofuel production.

PMID- 22138970
TI  - G1359A polymorphism in the cannabinoid receptor-1 gene is associated with the
      presence of coronary artery disease in patients with type 2 diabetes.
AB  - OBJECTIVE: Previous studies demonstrated that G1359A polymorphism of cannabinoid
      receptor-1 (CNR1) was associated with cardiovascular risk factors including
      obesity, insulin resistance, dyslipidemia, and inflammation, which are also risk
      factors for developing type 2 diabetes mellitus (T2DM). Therefore, this study was
      aimed to determine whether G1359A polymorphism of CNR1 is associated with T2DM
      and the presence of coronary artery disease (CAD) in patients with T2DM. METHODS:
      A total of 450 patients with T2DM (259 patients with CAD and 191 patients without
      CAD) and 94 healthy subjects were genotyped using polymerase chain reaction and
      restriction fragment length polymorphism method. RESULTS: No significant
      differences in genotype frequency of CNR1 were found between normal controls and
      patients with T2DM without CAD. GG genotype frequency of CNR1 was significantly
      higher in the patients with T2DM with CAD compared with those without CAD and
      healthy subjects (P = 0.003 and P = 0.005, respectively). Unconditional logistic
      regression analysis revealed that GG genotype was significantly associated with
      the presence of CAD in the patients with T2DM compared with GA and AA genotypes
      (odds ratio, 2.632; 95% confidence interval, 1.481-4.678; P < 0.001). In
      addition, GG genotype of CNR1 was significantly correlated with elevated levels
      of body mass index, systolic blood pressure, homeostasis model assessment of
      insulin resistance, and C-reactive protein, as well as decreased levels of high
      density lipoprotein cholesterol in patients with T2DM. CONCLUSIONS: G1359A
      polymorphism of CNR1 may be not associated with T2DM but may contribute to the
      genetic risk for the presence of CAD in patients with T2DM of Chinese Han
      population.

PMID- 22138969
TI  - Ectomycorrhizal fungus communities of Quercus liaotungensis Koidz of different
      ages in a northern China temperate forest.
AB  - Ectomycorrhizal (ECM) fungal communities of Quercus liaotungensis of different
      ages (seedlings, young trees and mature trees) in the growing seasons (June and
      September) between 2007 and 2009 were studied in a temperate forest of northern
      China. A total of 66 ECM fungal taxa were identified based on ECM morphotyping,
      PCR-RFLP, and DNA sequence data. Of these fungal taxa, 51 were Basidiomycetes
      (77.3%) and 15 were Ascomycetes (22.7%). Cenococcum geophilum was the dominant
      species. Thelephoraceae (16 taxa), Sebacinaceae (12 taxa) and Russulaceae (seven
      taxa) were the most species-rich and abundant ECM fungi, accounting for 19.5%,
      17.6% and 8.3% of the total ECM root tips, respectively. Results of multiple
      response permutation procedure (MRPP) analysis indicated that there were
      marginally significant effects of tree ages (A = 0.01801, P = 0.054) and growing
      seasons (A = 0.01908, P = 0.064) on the ECM fungal species composition of Q.
      liaotungensis in a temperate forest.

PMID- 22138971
TI  - Bioethanol from lignocellulosic biomass.
AB  - China is suffering from a sustained shortage of crude oil supply, making fuel
      ethanol and other biofuels alternative solutions for this issue. However, taking
      into account the country's large population and dwindling arable land due to
      rapid urbanization, it is apparent that current fuel ethanol production from
      grain-based feedstocks is not sustainable, and lignocellulosic biomass,
      particularly agricultural residues that are abundantly available in China, is the
      only choice for China to further expand its fuel ethanol production, provided
      economically viable processes can be developed. In this chapter, cutting edge
      progress in bioethanol is reviewed, with a focus on the understanding of the
      molecular structure of the feedstock, leading pretreatment technologies,
      enzymatic hydrolysis of the cellulose component and strategies for the co
      fermentation of the C5 and C6 sugars with engineered microorganisms. Finally,
      process integration and optimization is addressed with a case study on the COFCO
      Corporation's pilot plant, and challenges and perspectives for commercial
      production of bioethanol are highlighted.

PMID- 22138972
TI  - NHE1 activity contributes to migration and is necessary for proliferation of
      human gastric myofibroblasts.
AB  - Myofibroblasts play central roles in wound healing, deposition of the
      extracellular matrix and epithelial function. Their functions depend on migration
      and proliferation within the subepithelial matrix, which results in accelerated
      cellular metabolism. Upregulated metabolic pathways generate protons which need
      to be excreted to maintain intracellular pH (pH(i)). We isolated human gastric
      myofibroblasts (HGMs) from surgical specimens of five patients. Then we
      characterized, for the first time, the expression and functional activities of
      the Na(+)/H(+) exchanger (NHE) isoforms 1, 2 and 3, and the functional activities
      of the Na(+)/HCO(3)(-) cotransporter (NBC) and the anion exchanger (AE) in
      cultured HGMs using microfluorimetry, immunocytochemistry, reverse transcription
      polymerase chain reaction and immunoblot analysis. We showed that NHE1-3, NBC and
      AE activities are present in HGMs and that NHE1 is the most active of the NHEs.
      In scratch wound assays we also demonstrated (using the selective NHE inhibitor
      HOE-642) that carbachol and insulin like growth factor II (IGF-II) partly
      stimulate migration of HGMs in a NHE1-dependent manner. EdU incorporation assays
      revealed that IGF-II induces proliferation of HGMs which is inhibited by HOE-642.
      The results indicate that NHE1 is necessary for IGF-II-induced proliferation
      response of HGMs. Overall, we have characterized the pH(i) regulatory mechanisms
      of HGMs. In addition, we demonstrated that NHE1 activity contributes to both IGF
      II- and carbachol-stimulated migration and that it is obligatory for IGF-II
      induced proliferation of HGMs.

PMID- 22138973
TI  - N-3-oxo-decanoyl-L-homoserine-lactone activates auxin-induced adventitious root
      formation via hydrogen peroxide- and nitric oxide-dependent cyclic GMP signaling
      in mung bean.
AB  - N-Acyl-homoserine-lactones (AHLs) are bacterial quorum-sensing signaling
      molecules that regulate population density. Recent evidence demonstrates their
      roles in plant defense responses and root development. Hydrogen peroxide
      (H(2)O(2)), nitric oxide (NO), and cyclic GMP (cGMP) are essential messengers
      that participate in various plant physiological processes, but how these
      messengers modulate the plant response to N-acyl-homoserine-lactone signals
      remains poorly understood. Here, we show that the N-3-oxo-decanoyl-homoserine
      lactone (3-O-C10-HL), in contrast to its analog with an unsubstituted branch
      chain at the C3 position, efficiently stimulated the formation of adventitious
      roots and the expression of auxin-response genes in explants of mung bean (Vigna
      radiata) seedlings. This response was mimicked by the exogenous application of
      auxin, H(2)O(2), NO, or cGMP homologs but suppressed by treatment with scavengers
      or inhibitors of H(2)O(2), NO, or cGMP metabolism. The 3-O-C10-HL treatment
      enhanced auxin basipetal transport; this effect could be reversed by treatment
      with H(2)O(2) or NO scavengers but not by inhibitors of cGMP synthesis.
      Inhibiting 3-O-C10-HL-induced H(2)O(2) or NO accumulation impaired auxin- or 3-O
      C10-HL-induced cGMP synthesis; however, blocking cGMP synthesis did not affect
      auxin- or 3-O-C10-HL-induced H(2)O(2) or NO generation. Additionally, cGMP
      partially rescued the inhibitory effect of H(2)O(2) or NO scavengers on 3-O-C10
      HL-induced adventitious root development and auxin-response gene expression.
      These results suggest that 3-O-C10-HL, unlike its analog with an unmodified
      branch chain at the C3 position, can accelerate auxin-dependent adventitious root
      formation, possibly via H(2)O(2)- and NO-dependent cGMP signaling in mung bean
      seedlings.

PMID- 22138975
TI  - Touching the upper limit for ferromagnetic interactions in hetero-bridged
      dinuclear [Cu2(II)] complexes using a novel N5-dinucleating ligand bearing an
      endogenous monoatomic amido(R-NH(-))-bridging group.
AB  - A novel N(5)-dinucleating ligand 4-amino-3,5-bis(bipyridine-2-yl)-1,2,4-triazole
      allows the preparation for the first time, and under mild conditions, of single
      and mixed amido(R-NH(-))-bridged copper(II) complexes, the latter exhibiting very
      strong ferromagnetic coupling.

PMID- 22138974
TI  - Small RNA profiling in two Brassica napus cultivars identifies microRNAs with oil
      production- and development-correlated expression and new small RNA classes.
AB  - MicroRNAs (miRNAs) and small interfering RNAs are important regulators of plant
      development and seed formation, yet their population and abundance in the oil
      crop Brassica napus are still not well understood, especially at different
      developmental stages and among cultivars with varied seed oil contents. Here, we
      systematically analyzed the small RNA expression profiles of Brassica napus seeds
      at early embryonic developmental stages in high-oil-content and low-oil-content
      B. napus cultivars, both cultured in two environments. A total of 50 conserved
      miRNAs and 9 new miRNAs were identified, together with some new miRNA targets.
      Expression analysis revealed some miRNAs with varied expression levels in
      different seed oil content cultivars or at different embryonic developmental
      stages. A large number of 23-nucleotide small RNAs with specific nucleotide
      composition preferences were also identified, which may present new classes of
      functional small RNAs.

PMID- 22138976
TI  - Factors associated with the survival of patients with primary small cell
      carcinoma of the kidney.
AB  - BACKGROUND: Primary small cell carcinoma (SCC) of the kidney is rare, and the
      factors associated with the survival of these patients are yet to be elucidated.
      PATIENTS AND METHODS: We collected data on patients who were admitted to our
      hospital for SCC of the kidney in the last 22 years and of those in studies in
      the literature. Clinical characteristics were summarized using descriptive
      statistics. The associations of these factors with survival were evaluated using
      Cox regression models, and the hazard ratio of death was calculated. RESULTS:
      This study included 45 patients (8 admitted to our hospital and 37 from studies
      in the literature) with SCC of the kidney. The overall median survival time was
      9.9 months (range 6.9-31.6). Data on demographics, clinical symptoms, tumor
      staging, and tumor characteristics recorded at the time of diagnosis were not
      associated with survival. Among the different treatment modalities applied,
      cisplatin-based chemotherapy afforded a strong survival advantage (hazard ratio =
      0.35, p = 0.022). However, patients with early local recurrence (hazard ratio =
      19.13, p = 0.012) and early distant metastasis (hazard ratio = 10.93, p = 0.003)
      after primary treatment showed significantly poor survival. CONCLUSIONS: Patients
      with primary SCC of the kidney generally presented with large, advanced-stage
      tumors and showed poor survival. Early detection of the tumor, use of cisplatin
      based chemotherapy, and careful follow-up for local recurrence or frequent
      metastasis within 6 months after the primary treatment could be important for
      improving overall patient survival.

PMID- 22138977
TI  - Effect of the Hedgehog-inhibitor cyclopamine on mice with osteosarcoma pulmonary
      metastases.
AB  - Chemoresistant metastases of osteosarcoma in humans limit survival in
      approximately one third of patients. Furthermore, aggressive chemotherapy can
      lead to side effects and occurrence of secondary malignancies in long time
      survivors. Therefore, supplemental medical strategies are worthwhile. The well
      directed manipulation of cancer-signaling-cascades is an appealing approach.
      Targeting of the Hedgehog-pathway in cancer has led to promising results in vitro
      as well as in vivo in a number of different tumor types. Recently, the impact of
      cyclopamine, which inhibits Hedgehog signaling by binding to the receptor
      Smoothened, was shown in different human osteosarcoma cell lines in vitro and in
      vivo. In the present study we examined the influence of cyclopamine on early
      pulmonary metastases in vivo. Murine osteosarcoma cells, OS-50, were injected
      into the lateral tail vein of young BALB/c mice. Treatment with subcutaneous
      cyclopamine injections began after three days. Two weeks later, the animals were
      sacrificed and the number of pulmonary metastases was counted. We could observe a
      trend towards decreased metastases in the cyclopamine group (~20%). On the other
      hand, remarkable side effects were caused by the cyclopamine/ethanol/triolein
      preparation (mainly skin ulcerations).

PMID- 22138978
TI  - Cecal diverticulitis as a continuing diagnostic and management dilemma: a report
      of two cases in children.
AB  - Right-sided diverticulitis remains an exceedingly rare condition in the pediatric
      population. The clinical presentation mimics acute appendicitis, and the correct
      diagnosis is often difficult to make prior to operative exploration. We report
      two cases of cecal diverticulitis, and discuss the diagnosis and management of
      this disease, with a review of the literature.

PMID- 22138979
TI  - Retroperitoneal gastric duplication cyst: a case report and literature review.
AB  - A rare case of retroperitoneal gastric duplication is reported and discussed. An
      intra-abdominal cyst was detected at 31 weeks gestation and was followed up
      prenatally as a left sided duplex kidney. Post-natal ultrasound however, showed a
      normal kidney, but a cyst with features of enteric duplication in the left upper
      quadrant adjacent and compressing the kidney. Surgery was carried out during
      infancy and a retroperitoneal cyst was excised that contained heterotrophic
      gastric mucosa.

PMID- 22138980
TI  - Lithium cubane clusters as tetrahedral, square planar, and linear nodes for
      supramolecular assemblies.
AB  - The use of bifunctional ligands with phenol and pyridyl groups has been found to
      promote the formation of lithium cubane clusters intrinsically coded with
      specific preference for various hydrogen-bonding geometries including
      tetrahedral, square-planar, and linear modes through double, or even quadruple
      hydrogen bonding between adjacent nodes.

PMID- 22138981
TI  - Accumulation of the antibiotic phenazine-1-carboxylic acid in the rhizosphere of
      dryland cereals.
AB  - Natural antibiotics are thought to function in the defense, fitness,
      competitiveness, biocontrol activity, communication, and gene regulation of
      microorganisms. However, the scale and quantitative aspects of antibiotic
      production in natural settings are poorly understood. We addressed these
      fundamental questions by assessing the geographic distribution of indigenous
      phenazine-producing (Phz(+)) Pseudomonas spp. and the accumulation of the broad
      spectrum antibiotic phenazine-1-carboxylic acid (PCA) in the rhizosphere of wheat
      grown in the low-precipitation zone (<350 mm) of the Columbia Plateau and in
      adjacent, higher-precipitation areas. Plants were collected from 61 commercial
      wheat fields located within an area of about 22,000 km(2). Phz(+) Pseudomonas
      spp. were detected in all sampled fields, with mean population sizes ranging from
      log 3.2 to log 7.1 g(-1) (fresh weight) of roots. Linear regression analysis
      demonstrated a significant inverse relationship between annual precipitation and
      the proportion of plants colonized by Phz(+) Pseudomonas spp. (r(2) = 0.36, P =
      0.0001). PCA was detected at up to nanomolar concentrations in the rhizosphere of
      plants from 26 of 29 fields that were selected for antibiotic quantitation. There
      was a direct relationship between the amount of PCA extracted from the
      rhizosphere and the population density of Phz(+) pseudomonads (r(2) = 0.46, P =
      0.0006). This is the first demonstration of accumulation of significant
      quantities of a natural antibiotic across a terrestrial ecosystem. Our results
      strongly suggest that natural antibiotics can transiently accumulate in the plant
      rhizosphere in amounts sufficient not only for inter- and intraspecies signaling
      but also for the direct inhibition of sensitive organisms.

PMID- 22138982
TI  - Improvement of the redox balance increases L-valine production by Corynebacterium
      glutamicum under oxygen deprivation conditions.
AB  - Production of L-valine under oxygen deprivation conditions by Corynebacterium
      glutamicum lacking the lactate dehydrogenase gene ldhA and overexpressing the L
      valine biosynthesis genes ilvBNCDE was repressed. This was attributed to
      imbalanced cofactor production and consumption in the overall L-valine synthesis
      pathway: two moles of NADH was generated and two moles of NADPH was consumed per
      mole of L-valine produced from one mole of glucose. In order to solve this
      cofactor imbalance, the coenzyme requirement for L-valine synthesis was converted
      from NADPH to NADH via modification of acetohydroxy acid isomeroreductase encoded
      by ilvC and introduction of Lysinibacillus sphaericus leucine dehydrogenase in
      place of endogenous transaminase B, encoded by ilvE. The intracellular
      NADH/NAD(+) ratio significantly decreased, and glucose consumption and L-valine
      production drastically improved. Moreover, L-valine yield increased and succinate
      formation decreased concomitantly with the decreased intracellular redox state.
      These observations suggest that the intracellular NADH/NAD(+) ratio, i.e.,
      reoxidation of NADH, is the primary rate-limiting factor for L-valine production
      under oxygen deprivation conditions. The L-valine productivity and yield were
      even better and by-products derived from pyruvate further decreased as a result
      of a feedback resistance-inducing mutation in the acetohydroxy acid synthase
      encoded by ilvBN. The resultant strain produced 1,470 mM L-valine after 24 h with
      a yield of 0.63 mol mol of glucose(-1), and the L-valine productivity reached
      1,940 mM after 48 h.

PMID- 22138983
TI  - Presence of Bartonella species in wild carnivores of northern Spain.
AB  - The genus Bartonella was detected by PCR in 5.7% (12/212) of wild carnivores from
      Northern Spain. Based on hybridization and sequence analyses, Bartonella henselae
      was identified in a wildcat (Felis silvestris), Bartonella rochalimae in a red
      fox (Vulpes vulpes) and in a wolf (Canis lupus), and Bartonella sp. in badgers
      (Meles meles).

PMID- 22138984
TI  - Microbial community composition and dynamics of moving bed biofilm reactor
      systems treating municipal sewage.
AB  - Moving bed biofilm reactor (MBBR) systems are increasingly used for municipal and
      industrial wastewater treatment, yet in contrast to activated sludge (AS)
      systems, little is known about their constituent microbial communities. This
      study investigated the community composition of two municipal MBBR wastewater
      treatment plants (WWTPs) in Wellington, New Zealand. Monthly samples comprising
      biofilm and suspended biomass were collected over a 12-month period. Bacterial
      and archaeal community composition was determined using a full-cycle community
      approach, including analysis of 16S rRNA gene libraries, fluorescence in situ
      hybridization (FISH) and automated ribosomal intergenic spacer analysis (ARISA).
      Differences in microbial community structure and abundance were observed between
      the two WWTPs and between biofilm and suspended biomass. Biofilms from both
      plants were dominated by Clostridia and sulfate-reducing members of the
      Deltaproteobacteria (SRBs). FISH analyses indicated morphological differences in
      the Deltaproteobacteria detected at the two plants and also revealed distinctive
      clustering between SRBs and members of the Methanosarcinales, which were the only
      Archaea detected and were present in low abundance (<5%). Biovolume estimates of
      the SRBs were higher in biofilm samples from one of the WWTPs which receives both
      domestic and industrial waste and is influenced by seawater infiltration. The
      suspended communities from both plants were diverse and dominated by aerobic
      members of the Gammaproteobacteria and Betaproteobacteria. This study represents
      the first detailed analysis of microbial communities in full-scale MBBR systems
      and indicates that this process selects for distinctive biofilm and planktonic
      communities, both of which differ from those found in conventional AS systems.

PMID- 22138985
TI  - Development of a rapid and sensitive method combining a cellulose ester
      microfilter and a real-time quantitative PCR assay to detect Campylobacter jejuni
      and Campylobacter coli in 20 liters of drinking water or low-turbidity waters.
AB  - Investigations of Campylobacter jejuni and Campylobacter coli in samples of
      drinking water suspected of being at the origin of an outbreak very often lead to
      negative results. One of the reasons for this failure is the small volume of
      water typically used for detecting these pathogens (10 to 1,000 ml). The
      efficiencies of three microfilters and different elution procedures were
      determined using real-time quantitative PCR to propose a procedure allowing
      detection of Campylobacter in 20 liters of drinking water or low-turbidity water
      samples. The results showed that more than 80% of the bacteria inoculated in 1
      liter of drinking water were retained on each microfilter. An elution with a
      solution containing 3% beef extract, 0.05 M glycine at pH 9, combined with direct
      extraction of the bacterial genomes retained on the cellulose ester microfilter,
      allowed recovery of 87.3% (+/-22% [standard deviation]) of Campylobacter per 1
      liter of tap water. Recoveries obtained from 20-liter volumes of tap water spiked
      with a C. coli strain were 69.5% (+/-10.3%) and 78.5% (+/-15.1%) for 91 CFU and
      36 CFU, respectively. Finally, tests performed on eight samples of 20 liters of
      groundwater collected from an alluvial well used for the production of drinking
      water revealed the presence of C. jejuni and C. coli genomes, whereas no bacteria
      were detected with the normative culture method in volumes ranging from 10 to
      1,000 ml. In the absence of available epidemiological data and information on
      bacterial viability, these last results indicate only that the water resource is
      not protected from contamination by Campylobacter.

PMID- 22138986
TI  - Identification of plasmalogens in the cytoplasmic membrane of Bifidobacterium
      animalis subsp. lactis.
AB  - Plasmalogens are ether-linked lipids that may influence oxidative stress
      resistance of eukaryotic cell membranes. Since bacterial membrane composition can
      influence environmental stress resistance, we explored the prevalence of
      plasmalogens in the cytoplasmic membrane of Bifidobacterium animalis subsp.
      lactis. Results showed plasmalogens are a major component of the B. animalis
      subsp. lactis membrane.

PMID- 22138987
TI  - Surveillance study of hepatitis A virus RNA on fig and date samples.
AB  - A total of 91 fig and 185 date samples were analyzed by reverse transcription
      (RT) real-time PCR for the presence of hepatitis A virus (HAV) RNA. Two batches
      of dates tested positive, and the HAV RNA detected was genotyped as IA. These
      findings warrant further development of methods applicable to food which is
      consumed untreated and is exported from countries in which HAV is endemic.

PMID- 22138988
TI  - Transcriptome dynamics of Pseudomonas putida KT2440 under water stress.
AB  - Water deprivation can be a major stressor to microbial life in surface and
      subsurface soil. In unsaturated soils, the matric potential (Psi(m)) is often the
      main component of the water potential, which measures the thermodynamic
      availability of water. A low matric potential usually translates into water
      forming thin liquid films in the soil pores. Little is known of how bacteria
      respond to such conditions, where, in addition to facing water deprivation that
      might impair their metabolism, they have to adapt their dispersal strategy as
      swimming motility may be compromised. Using the pressurized porous surface model
      (PPSM), which allows creation of thin liquid films by controlling Psi(m), we
      examined the transcriptome dynamics of Pseudomonas putida KT2440. We identified
      the differentially expressed genes in cells exposed to a mild matric stress (-0.4
      MPa) for 4, 24, or 72 h. The major response was detected at 4 h before gradually
      disappearing. Upregulation of alginate genes was notable in this early response.
      Flagellar genes were not downregulated, and the microarray data even suggested
      increasing expression as the stress prolonged. Moreover, we tested the effect of
      polyethylene glycol 8000 (PEG 8000), a nonpermeating solute often used to
      simulate Psi(m), on the gene expression profile and detected a different profile
      than that observed by directly imposing Psi(m). This study is the first
      transcriptome profiling of KT2440 under directly controlled Psi(m) and also the
      first to show the difference in gene expression profiles between a PEG 8000
      simulated and a directly controlled Psi(m).

PMID- 22138989
TI  - Hydrazine synthase, a unique phylomarker with which to study the presence and
      biodiversity of anammox bacteria.
AB  - Anaerobic ammonium-oxidizing (anammox) bacteria play an important role in the
      biogeochemical cycling of nitrogen. They derive their energy for growth from the
      conversion of ammonium and nitrite into dinitrogen gas in the complete absence of
      oxygen. Several methods have been used to detect the presence and activity of
      anammox bacteria in the environment, including 16S rRNA gene-based approaches.
      The use of the 16S rRNA gene to study biodiversity has the disadvantage that it
      is not directly related to the physiology of the target organism and that current
      primers do not completely capture the anammox diversity. Here we report the
      development of PCR primer sets targeting a subunit of the hydrazine synthase
      (hzsA), which represents a unique phylogenetic marker for anammox bacteria. The
      tested primers were able to retrieve hzsA gene sequences from anammox enrichment
      cultures, full-scale anammox wastewater treatment systems, and a variety of
      freshwater and marine environmental samples, covering all known anammox genera.

PMID- 22138990
TI  - Distribution of microbial biomass and potential for anaerobic respiration in
      Hanford Site 300 Area subsurface sediment.
AB  - Subsurface sediments were recovered from a 52-m-deep borehole cored in the 300
      Area of the Hanford Site in southeastern Washington State to assess the potential
      for biogeochemical transformation of radionuclide contaminants. Microbial
      analyses were made on 17 sediment samples traversing multiple geological units:
      the oxic coarse-grained Hanford formation (9 to 17.4 m), the oxic fine-grained
      upper Ringold formation (17.7 to 18.1 m), and the reduced Ringold formation (18.3
      to 52 m). Microbial biomass (measured as phospholipid fatty acids) ranged from 7
      to 974 pmols per g in discrete samples, with the highest numbers found in the
      Hanford formation. On average, strata below 17.4 m had 13-fold less biomass than
      those from shallower strata. The nosZ gene that encodes nitrous oxide reductase
      (measured by quantitative real-time PCR) had an abundance of 5 to 17 relative to
      that of total 16S rRNA genes below 18.3 m and <5 above 18.1 m. Most nosZ
      sequences were affiliated with Ochrobactrum anthropi (97 sequence similarity) or
      had a nearest neighbor of Achromobacter xylosoxidans (90 similarity). Passive
      multilevel sampling of groundwater geochemistry demonstrated a redox gradient in
      the 1.5-m region between the Hanford-Ringold formation contact and the Ringold
      oxic-anoxic interface. Within this zone, copies of the dsrA gene and
      Geobacteraceae had the highest relative abundance. The majority of dsrA genes
      detected near the interface were related to Desulfotomaculum spp. These analyses
      indicate that the region just below the contact between the Hanford and Ringold
      formations is a zone of active biogeochemical redox cycling.

PMID- 22138991
TI  - Binding of human GII.4 norovirus virus-like particles to carbohydrates of romaine
      lettuce leaf cell wall materials.
AB  - Norovirus (NoV) genogroup II genotype 4 (GII.4) strains are the dominant cause of
      the majority of food-borne outbreaks, including those that involve leafy greens,
      such as lettuce. Since human NoVs use carbohydrates of histo-blood group antigens
      as receptors/coreceptors, we examined the role of carbohydrates in the attachment
      of NoV to lettuce leaves by using virus-like particles (VLPs) of a human
      NoV/GII.4 strain. Immunofluorescence analysis showed that the VLPs attached to
      the leaf surface, especially to cut edges, stomata, and along minor veins.
      Binding was quantified using enzyme-linked immunosorbent assay (ELISA) performed
      on cell wall materials (CWM) from innermost younger leaves and outermost lamina
      of older leaves. The binding to CWM of older leaves was significantly (P < 0.05)
      higher (1.5- to 2-fold) than that to CWM of younger leaves. Disrupting the
      carbohydrates of CWM or porcine gastric mucin (PGM) (a carbohydrate control)
      using 100 mM sodium periodate (NaIO(4)) significantly decreased the binding an
      average of 17% in younger leaves, 43% in older leaves, and 92% for PGM. In
      addition, lectins recognizing GalNAc, GlcNAc, and sialic acid at 100 MUg/ml
      significantly decreased the binding an average of 41%, 33%, and 20% on CWM of
      older leaves but had no effect on younger leaves. Lectins recognizing alpha-D
      Gal, alpha-D-Man/alpha-D-Glc, and alpha-L-Fuc showed significant inhibition on
      CWM of older leaves as well as that of younger leaves. All lectins, except for
      the lectin recognizing alpha-D-Gal, significantly inhibited NoV VLP binding to
      PGM. Collectively, our results indicate that NoV VLPs bind to lettuce CWM by
      utilizing multiple carbohydrate moieties. This binding may enhance virus
      persistence on the leaf surface and prevent effective decontamination.

PMID- 22138992
TI  - Cultivated single-stranded DNA phages that infect marine Bacteroidetes prove
      difficult to detect with DNA-binding stains.
AB  - This is the first description of cultivated icosahedral single-stranded DNA
      (ssDNA) phages isolated on heterotrophic marine bacterioplankton and with
      Bacteroidetes hosts. None of the 8 phages stained well with DNA-binding stains,
      suggesting that in situ abundances of ssDNA phages are drastically underestimated
      using conventional methods for enumeration.

PMID- 22138993
TI  - Inactivation of template-directed misfolding of infectious prion protein by
      ozone.
AB  - Misfolded prions (PrP(Sc)) are well known for their resistance to conventional
      decontamination processes. The potential risk of contamination of the water
      environment, as a result of disposal of specified risk materials (SRM), has
      raised public concerns. Ozone is commonly utilized in the water industry for
      inactivation of microbial contaminants and was tested in this study for its
      ability to inactivate prions (263K hamster scrapie = PrP(Sc)). Treatment
      variables included initial ozone dose (7.6 to 25.7 mg/liter), contact time (5 s
      and 5 min), temperature (4 degrees C and 20 degrees C), and pH (pH 4.4, 6.0, and
      8.0). Exposure of dilute suspensions of the infected 263K hamster brain
      homogenates (IBH) (0.01%) to ozone resulted in the in vitro destruction of the
      templating properties of PrP(Sc), as measured by the protein misfolding cyclic
      amplification (PMCA) assay. The highest levels of prion inactivation (>=4
      log(10)) were observed with ozone doses of 13.0 mg/liter, at pH 4.4 and 20
      degrees C, resulting in a CT (the product of residual ozone concentration and
      contact time) value as low as 0.59 mg . liter(-1) min. A comparison of ozone CT
      requirements among various pathogens suggests that prions are more susceptible to
      ozone degradation than some model bacteria and protozoa and that ozone treatment
      may be an effective solution for inactivating prions in water and wastewater.

PMID- 22138994
TI  - S-layer homology domain proteins Csac_0678 and Csac_2722 are implicated in plant
      polysaccharide deconstruction by the extremely thermophilic bacterium
      Caldicellulosiruptor saccharolyticus.
AB  - The genus Caldicellulosiruptor contains extremely thermophilic bacteria that grow
      on plant polysaccharides. The genomes of Caldicellulosiruptor species reveal
      certain surface layer homology (SLH) domain proteins that have distinguishing
      features, pointing to a role in lignocellulose deconstruction. Two of these
      proteins in Caldicellulosiruptor saccharolyticus (Csac_0678 and Csac_2722) were
      examined from this perspective. In addition to three contiguous SLH domains, the
      Csac_0678 gene encodes a glycoside hydrolase family 5 (GH5) catalytic domain and
      a family 28 carbohydrate-binding module (CBM); orthologs to Csac_0678 could be
      identified in all genome-sequenced Caldicellulosiruptor species. Recombinant
      Csac_0678 was optimally active at 75 degrees C and pH 5.0, exhibiting both
      endoglucanase and xylanase activities. SLH domain removal did not impact
      Csac_0678 GH activity, but deletion of the CBM28 domain eliminated binding to
      crystalline cellulose and rendered the enzyme inactive on this substrate.
      Csac_2722 is the largest open reading frame (ORF) in the C. saccharolyticus
      genome (predicted molecular mass of 286,516 kDa) and contains two putative sugar
      binding domains, two Big4 domains (bacterial domains with an immunoglobulin [Ig]
      like fold), and a cadherin-like (Cd) domain. Recombinant Csac_2722, lacking the
      SLH and Cd domains, bound to cellulose and had detectable carboxymethylcellulose
      (CMC) hydrolytic activity. Antibodies directed against Csac_0678 and Csac_2722
      confirmed that these proteins bound to the C. saccharolyticus S-layer. Their
      cellular localization and functional biochemical properties indicate roles for
      Csac_0678 and Csac_2722 in recruitment and hydrolysis of complex polysaccharides
      and the deconstruction of lignocellulosic biomass. Furthermore, these results
      suggest that related SLH domain proteins in other Caldicellulosiruptor genomes
      may also be important contributors to plant biomass utilization.

PMID- 22138995
TI  - Bifidobacterium longum subsp. infantis ATCC 15697 alpha-fucosidases are active on
      fucosylated human milk oligosaccharides.
AB  - Bifidobacterium longum subsp. infantis ATCC 15697 utilizes several small-mass
      neutral human milk oligosaccharides (HMOs), several of which are fucosylated.
      Whereas previous studies focused on endpoint consumption, a temporal glycan
      consumption profile revealed a time-dependent effect. Specifically, among
      preferred HMOs, tetraose was favored early in fermentation, with other
      oligosaccharides consumed slightly later. In order to utilize fucosylated
      oligosaccharides, ATCC 15697 possesses several fucosidases, implicating GH29 and
      GH95 alpha-L-fucosidases in a gene cluster dedicated to HMO metabolism.
      Evaluation of the biochemical kinetics demonstrated that ATCC 15697 expresses
      three fucosidases with a high turnover rate. Moreover, several ATCC 15697
      fucosidases are active on the linkages inherent to the HMO molecule. Finally, the
      HMO cluster GH29 alpha-L-fucosidase possesses a crystal structure that is similar
      to previously characterized fucosidases.

PMID- 22138996
TI  - Isolation and characterization of enterocin W, a novel two-peptide lantibiotic
      produced by Enterococcus faecalis NKR-4-1.
AB  - Enterococcus faecalis NKR-4-1 isolated from pla-ra produces a novel two-peptide
      lantibiotic, termed enterocin W, comprising Walpha and Wbeta. The structure of
      enterocin W exhibited similarity with that of plantaricin W. The two peptides
      acted synergistically, and their order of binding to the cell membrane was
      important for their inhibitory activity.

PMID- 22138997
TI  - Green fluorescent protein-labeled monitoring tool to quantify conjugative plasmid
      transfer between Gram-positive and Gram-negative bacteria.
AB  - On the basis of pIP501, a green fluorescent protein (GFP)-tagged monitoring tool
      was constructed for quantifying plasmid mobilization among Gram-positive bacteria
      and between Gram-positive Enterococcus faecalis and Gram-negative Escherichia
      coli. Furthermore, retromobilization of the GFP-tagged monitoring tool was shown
      from E. faecalis OG1X into the clinical isolate E. faecalis T9.

PMID- 22138998
TI  - False-negative rate and recovery efficiency performance of a validated sponge
      wipe sampling method.
AB  - Recovery of spores from environmental surfaces varies due to sampling and
      analysis methods, spore size and characteristics, surface materials, and
      environmental conditions. Tests were performed to evaluate a new, validated
      sponge wipe method using Bacillus atrophaeus spores. Testing evaluated the
      effects of spore concentration and surface material on recovery efficiency (RE),
      false-negative rate (FNR), limit of detection (LOD), and their uncertainties.
      Ceramic tile and stainless steel had the highest mean RE values (48.9 and 48.1%,
      respectively). Faux leather, vinyl tile, and painted wood had mean RE values of
      30.3, 25.6, and 25.5, respectively, while plastic had the lowest mean RE (9.8%).
      Results show roughly linear dependences of RE and FNR on surface roughness, with
      smoother surfaces resulting in higher mean REs and lower FNRs. REs were not
      influenced by the low spore concentrations tested (3.10 * 10(-3) to 1.86
      CFU/cm(2)). Stainless steel had the lowest mean FNR (0.123), and plastic had the
      highest mean FNR (0.479). The LOD(90) (>=1 CFU detected 90% of the time) varied
      with surface material, from 0.015 CFU/cm(2) on stainless steel up to 0.039 on
      plastic. It may be possible to improve sampling results by considering surface
      roughness in selecting sampling locations and interpreting spore recovery data.
      Further, FNR values (calculated as a function of concentration and surface
      material) can be used presampling to calculate the numbers of samples for
      statistical sampling plans with desired performance and postsampling to calculate
      the confidence in characterization and clearance decisions.

PMID- 22138999
TI  - Atypical Listeria monocytogenes serotype 4b strains harboring a lineage II
      specific gene cassette.
AB  - Listeria monocytogenes is the etiological agent of listeriosis, a severe food
      borne illness. The population of L. monocytogenes is divided into four lineages
      (I to IV), and serotype 4b in lineage I has been involved in numerous outbreaks.
      Several serotype 4b epidemic-associated clonal groups (ECI, -II, and -Ia) have
      been identified. In this study, we characterized a panel of strains of serotype
      4b that produced atypical results with a serotype-specific multiplex PCR and
      possessed the lmo0734 to lmo0739 gene cassette that had been thought to be
      specific to lineage II. The cassette was harbored in a genomically syntenic locus
      in these isolates and in lineage II strains. Three distinct clonal groups (groups
      1 to 3) were identified among these isolates based on single-nucleotide
      polymorphism-based multilocus genotyping (MLGT) and DNA hybridization data.
      Groups 1 and 2 had MLGT haplotypes previously encountered among clinical isolates
      and were composed of clinical isolates from multiple states in the United States.
      In contrast, group 3 consisted of clinical and environmental isolates solely from
      North Carolina and exhibited a novel haplotype. In addition, all group 3 isolates
      had DNA that was resistant to MboI, suggesting methylation of adenines at GATC
      sites. Sequence analysis of the lmo0734 to lmo0739 gene cassette from two strains
      (group 1 and group 3) revealed that the genes were highly conserved (>99%
      identity). The data suggest relatively recent horizontal gene transfer from
      lineage II L. monocytogenes into L. monocytogenes serotype 4b and subsequent
      dissemination among at least three distinct clonal groups of L. monocytogenes
      serotype 4b, one of which exhibits restrictions in regional distribution.

PMID- 22139000
TI  - Characterization of DC1, a broad-host-range Bcep22-like podovirus.
AB  - Bcep22-like phages are a recently described group of podoviruses that infect
      strains of Burkholderia cenocepacia. We have isolated and characterized a novel
      member of this group named DC1. This podovirus shows many genomic similarities to
      BcepIL02 and Bcep22, but it infects strains belonging to multiple Burkholderia
      cepacia complex (BCC) species.

PMID- 22139001
TI  - Porticoccus hydrocarbonoclasticus sp. nov., an aromatic hydrocarbon-degrading
      bacterium identified in laboratory cultures of marine phytoplankton.
AB  - A marine bacterium, designated strain MCTG13d, was isolated from a laboratory
      culture of the dinoflagellate Lingulodinium polyedrum CCAP1121/2 by enrichment
      with polycyclic aromatic hydrocarbons (PAHs) as the sole carbon source. Based on
      16S rRNA gene sequence comparisons, the strain was most closely related to
      Porticoccus litoralis IMCC2115(T) (96.5%) and to members of the genera
      Microbulbifer (91.4 to 93.7%) and Marinimicrobium (90.4 to 92.0%). Phylogenetic
      trees showed that the strain clustered in a distinct phyletic line in the class
      Gammaproteobacteria for which P. litoralis is presently the sole cultured
      representative. The strain was strictly aerobic, rod shaped, Gram negative, and
      halophilic. Notably, it was able to utilize hydrocarbons as sole sources of
      carbon and energy, whereas sugars did not serve as growth substrates. The
      predominant isoprenoid quinone of strain MCTG13d was Q-8, and the dominant fatty
      acids were C(16:1omega7c), C(18:1omega7c), and C(16:0). DNA G+C content for the
      isolate was 54.9 +/- 0.42 mol%. Quantitative PCR primers targeting the 16S rRNA
      gene of this strain showed that this organism was common in other laboratory
      cultures of marine phytoplankton. On the basis of phenotypic and genotypic
      characteristics, strain MCTG13d represents a novel species of Porticoccus, for
      which the name Porticoccus hydrocarbonoclasticus sp. nov. is proposed. The
      discovery of this highly specialized hydrocarbon-degrading bacterium living in
      association with marine phytoplankton suggests that phytoplankton represent a
      previously unrecognized biotope of novel bacterial taxa that degrade hydrocarbons
      in the ocean.

PMID- 22139002
TI  - Survival of host-associated bacteroidales cells and their relationship with
      Enterococcus spp., Campylobacter jejuni, Salmonella enterica serovar Typhimurium,
      and adenovirus in freshwater microcosms as measured by propidium monoazide
      quantitative PCR.
AB  - The ideal host-associated genetic fecal marker would be capable of predicting the
      presence of specific pathogens of concern. Flowthrough freshwater microcosms
      containing mixed feces and inocula of the pathogens Campylobacter jejuni,
      Salmonella enterica serovar Typhimurium, and adenovirus were placed at ambient
      temperature in the presence and absence of diurnal sunlight. The total
      Enterococcus DNA increased during the early periods (23 h) under sunlight
      exposure, even though cultivable Enterococcus and DNA in intact cells, as
      measured by propidium monoazide (PMA), decreased with first-order kinetics during
      the entire period. We found a significant difference in the decay of host
      associated Bacteroidales cells between sunlight exposure and dark conditions (P
      value < 0.05), whereas the persistence of host-associated Bacteroidales DNA was
      comparable. The 2-log reduction times of adenovirus were 72 h for sunlight
      exposure and 99 h for dark conditions with similar decay rate constants (P value
      = 0.13). The persistences of fecal Bacteroidales cells and Campylobacter cells
      exposed to sunlight were similar, and host-associated Bacteroidales DNA and
      waterborne pathogen DNA were degraded at comparable rates (P values > 0.05).
      Overall, the ratio of quantitative PCR (qPCR) cycle threshold (C(T)) values with
      and without PMA treatment was indicative of the time elapsed since inoculation of
      the microcosm with (i) fecal material from different animal sources based on host
      associated Bacteroidales and (ii) pure cultures of bacterial pathogens. The use
      of both PMA-qPCR and qPCR may yield more realistic information about recent
      sources of fecal contamination and result in improved prediction of waterborne
      pathogens and assessment of health risk.

PMID- 22139003
TI  - Human vascular endothelial cells reduce sphingosylphosphorylcholine-induced
      smooth muscle cell contraction in co-culture system through integrin beta4 and
      Fyn.
AB  - AIM: In vascular strips, the adjacent endothelial cells modulate the contraction
      of vascular smooth muscle cells (VSMCs) induced by sphingosylphosphorylcholine
      (SPC) through nitric oxide (NO). The aim of this study was to elucidate the
      mechanisms by which vascular endothelial cells (VECs) reduce the SPC-induced
      contraction of VSMCs in a co-culture system. METHODS: Human umbilical VECs and
      VSMCs were co-cultured. The VECs were transfected with integrin beta4- or Fyn
      specific siRNA. The areas of VSMCs that are involved in cell contractility were
      quantified using the Leica confocal software and collagen contractility assay.
      The production of NO in VECs was measured in the cell supernatants using NO
      Detection Kit. The levels of integrin beta4 and Fyn in VECs and the levels of Rho
      kinase (ROCK) in VSMC were detected using immunofluorescence assays or Western
      blots. RESULTS: Co-culture with VECs reduced the contraction of VSMCs induced by
      SPC (30 MUmol/L). The down-regulation of integrin beta4 or Fyn in VECs by the
      specific siRNA (20 nmol/L) was able to counteract the effects of VECs on the SPC
      induced VSMC contractions. Furthermore, the integrin beta4-specific siRNA (20 and
      40 nmol/L) significantly reduced the level of Fyn protein and the production of
      NO in VECs, while increased the level of ROCK in VSMCs that had been stimulated
      by SPC. CONCLUSION: The VECs reduced the SPC-induced contraction of VSMCs in the
      co-culture system through integrin beta4 and Fyn proteins. In this process, NO
      may be the factor downstream of integrin beta4 in VECs, while ROCK may be the key
      protein regulating the contraction of VSMCs.

PMID- 22139005
TI  - aepEX monitor for the measurement of hypnotic depth in patients undergoing
      balanced xenon anaesthesia.
AB  - BACKGROUND: Previously, we showed a significant difference in the measurements of
      hypnotic depth by the bispectral index (BIS) and auditory-evoked potentials
      (AEPs) using the A-line autoregressive index during xenon anaesthesia. In the
      present study, we evaluate the alternative AEP-based auditory-evoked potential
      index (aepEX) for the measurement of hypnotic depth in patients undergoing
      general anaesthesia with xenon. METHODS: Forty-two patients undergoing elective
      abdominal surgery were enrolled in this controlled, double-blinded, randomized,
      clinical study. Patients were randomized to receive either xenon (n=21) or
      sevoflurane anaesthesia (n=21). During anaesthesia, BIS values were recorded
      simultaneously with the aepEX monitoring. The anaesthetist performing the
      anaesthesia was blinded to the hypnotic depth monitors. After surgery, the
      incidence of recalls and awareness was evaluated. RESULTS: Patients'
      characteristics such as gender, age, and weight did not differ between the
      groups. The aepEX and BIS values behaved similarly during anaesthesia. The
      comparison of aepEX values during xenon and sevoflurane anaesthesia revealed
      significantly lower aepEX values in the xenon group after 25 min [xenon: 32.9
      (4.8) vs sevoflurane: 39.3 (9.0); P=0.008] and after 35 min [xenon: 31.4 (6.6) vs
      sevoflurane: 37.0 (6.8); P=0.012]. During anaesthesia, aepEX values correlated
      with the clinical evaluation of depth of anaesthesia (e.g. >20% changes of the
      baseline arterial pressure or heart rate, spontaneous breathing and/or
      intolerance of mechanical ventilation, coughing, abdominal pressing, sweating,
      eye tearing). CONCLUSIONS: We found the aepEX monitor to provide index in the
      range of adequate depth of xenon anaesthesia, when combined with remifentanil
      infusion in intubated patients undergoing elective abdominal surgery.

PMID- 22139004
TI  - Pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin
      loaded poly(lactic-co-glycolic acid) microspheres in rats.
AB  - AIM: To characterize the pharmacokinetic and pharmacodynamic profiles of the
      recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid)
      (PLGA) microspheres in rats. METHODS: The rhEPO-loaded microspheres were prepared
      using a solid-in-oil-in-water emulsion method. Pharmacokinetics and
      pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague
      Dawley rats. The serum rhEPO level was determined with ELISA. The level of anti
      rhEPO antibody in the serum was measured to assess the immunogenicity of rhEPO
      released from the microspheres. RESULTS: rhEPO was almost completely released
      from the PLGA microspheres in vitro, following zero-order release kinetics over
      approximately 30 d. After intramuscular injection (10,000 or 30,000 IU rhEPO/kg)
      in the rats, the serum rhEPO concentration reached maximum levels on d 1, then
      decreased gradually and was maintained at nearly steady levels for approximately
      4 weeks. Furthermore, the release of rhEPO from the PLGA microspheres was found
      to be controlled mainly by a dissolution/diffusion mechanism. A good linear
      correlation (R(2)=0.98) was obtained between the in vitro and in vivo release
      data. A single intramuscular injection of the rhEPO-loaded PLGA microspheres
      (10,000 or 30,000 IU rhEPO/kg) in the rats resulted in elevated hemoglobin and
      red blood cell concentrations for more than 28 d. Moreover, the immunogenicity of
      rhEPO released from the PLGA microspheres was comparable with that of the
      unencapsulated rhEPO. CONCLUSION: The results prove the feasibility of using the
      PLGA-based microspheres to deliver rhEPO for approximately 1 month.

PMID- 22139006
TI  - Two new species of Contracaecum Railliet & Henry, 1912 (Nematoda: Anisakidae), C.
      fagerholmi n. sp. and C. rudolphii F from the brown pelican Pelecanus
      occidentalis in the northern Gulf of Mexico.
AB  - DNA sequencing of the nuclear ribosomal DNA internal transcribed spacers (ITS)
      and mitochondrial rrnS and cox2 genes, and analysis of polymorphisms in
      restriction profiles in the ITS and rrnS, were used to characterise anisakid
      nematodes belonging to Contracaecum Railliet & Henry, 1912 infecting the brown
      pelican Pelecanus occidentalis (L.) in Galveston Bay, Texas and Sarasota Bay,
      Florida. Molecular data led to the detection of two new species: Contracaecum
      fagerholmi n. sp., which was also supported by clear morphological evidence, and
      Contracaecum rudolphii F, a new cryptic species within the Contracaecum rudolphii
      Hartwich, 1964 complex. Bayesian phylogenetic analysis demonstrated that C.
      fagerholmi and C. rudolphii F form two well-separated clusters, with C.
      fagerholmi being closely related to Contracaecum bioccai Mattiucci et al., 2008
      and C. rudolphii F being included in the C. rudolphii complex. C. fagerholmi can
      be readily differentiated morphologically from all of its congeners, other than
      C. microcephalum (Rudolphii 1809) and the five currently recognised members of
      the C. rudolphii complex (C. rudolphii A, B, C, D and E). C. fagerholmi differs
      from C. microcephalum in the length of the spicules and the shape of the distal
      tip of the spicules, and from C. rudolphii (sensu lato) in the shape and size of
      the ventro-lateral and dorsal lips and by having interlabia which are not
      distally bifurcate. Further studies are needed to determine which morphological
      characteristics can be used to distinguish the cryptic species of the C.
      rudolphii complex in order to assign them with formal names. The recovery of a
      third species, C. bioccai, from the brown pelican confirms its occurrence in this
      host and extends its known geographical distribution.

PMID- 22139007
TI  - A synopsis of the species of Myxobolus Butschli, 1882 (Myxozoa: Bivalvulida)
      parasitising Indian fishes and a revised dichotomous key to myxosporean genera.
AB  - A synopsis of 131 nominal species of Myxobolus Butschli, 1882 (Myxozoa:
      Myxosporea: Myxobolidae) reported from India is presented. For each species, the
      relevant morphometric and morphological data are indicated, as well as the
      host(s), site(s) of infection within the host and locality data. A revised
      dichotomous key of 59 genera of the class Myxosporea has also been included. This
      key incorporates 10 additional genera to that proposed in 1991 by Lom & Dykova.

PMID- 22139008
TI  - Ophiotaenia bungari n. sp. (Cestoda), a parasite of Bungarus fasciatus
      (Schneider) (Ophidia: Elapidae) from Vietnam, with comments on relative ovarian
      size as a new and potentially useful diagnostic character for proteocephalidean
      tapeworms.
AB  - Ophiotaenia bungari n. sp. (Cestoda: Proteocephalidea) is described from the
      intestine of the banded krait Bungarus fasciatus (Schneider) (Ophidia: Elapidae)
      in Vietnam. The new species differs from all but three Ophiotaenia species
      parasitic in Asian reptiles in the possession of a glandular apical organ. It
      differs from O. andersoni Jensen, Schmidt & Kuntz, 1983 in the position of the
      vagina in relation to the cirrus-sac (anterior and posterior in O. bungari versus
      anterior only in the latter species), in the cirrus-sac/proglottis width ratio
      (29-38 versus 50%) and by having more testes (100-150 versus 42-116 in O.
      andersoni); from O. chattoraji Srivastava, 1980 in the number of uterine
      diverticula (50-65 versus 10-26) and in the cirrus-sac/proglottis width ratio (29
      38 versus 22%); and from O. rhabdophidis (Burt, 1937) by having more uterine
      diverticula (50-65 versus 30-45), by the cirrus-sac/proglottis width ratio (29-38
      versus 20-25%) and by the width of the scolex (360-420 versus 130-187 MUm). The
      taxonomic importance of the relative size of the ovary (i.e. the ratio of the
      ovarian size in relation to that of the entire proglottis), a character
      previously not used in the systematics of proteocephalidean cestodes, is
      discussed. Comparison of measurements of all of the nominal species of
      Ophiotaenia La Rue, 1911 and Proteocephalus Weinland, 1858 (c.135 species) has
      shown that the ovary of species parasitic in snakes in the Americas, Africa, Asia
      and Australia is not only considerably smaller than that of congeneric species
      from European hosts, but also smaller than in all species of Proteocephalus
      parasitic in teleost fishes throughout the world.

PMID- 22139009
TI  - Acuaria paraguayensis n. sp. from Sirystes sibilator (Aves: Tyrannidae) in
      Paraguay and a redescription of A. mamillaris (Molin, 1860) from Cyanocorax
      cayanus (Corvidae) in Brazil, with a key to the species of Acuaria Bremser, 1811
      (Nematoda: Acuariidae) in the New World.
AB  - Acuaria paraguayensis n. sp. is described on the basis of specimens from Sirystes
      sibilator (Vieillot) (Aves: Passeriformes, Tyrannidae) in Paraguay. In addition,
      A. mamillaris (Molin, 1860) from Cyanocorax cayanus (L.) (Corvidae) in Brazil is
      redescribed on the basis of its type-series from the collection of the
      Naturhistorisches Museum, Vienna. A review of the species of Acuaria Bremser,
      1811 in the New World is presented. Currently, 16 species belong to this genus,
      which are mostly parasitic in passeriform birds (one record in piciform birds).
      An identification key to the species of Acuaria occurring in the New World is
      presented. Acuaria multispinosa (Vigueras, 1938) originally described from
      Botaurus lentiginosus (Rackett) (Ardeidae) in Cuba, also known from various
      herons (Ciconiiformes, Ardeidae) in southern states of the USA, does not
      correspond to the generic diagnosis of Acuaria and is considered a species
      incertae sedis. Acuaria gracilis var. sturni Boyd, 1951 is elevated to full
      species rank as Acuaria sturni Boyd, 1951.

PMID- 22139010
TI  - A new species of Heterocotyle Scott, 1904 (Monogenea: Monocotylidae) from the
      gills of Dasyatis guttata (Dasyatidae) in southwestern Atlantic waters off Rio de
      Janeiro, Brazil.
AB  - Heterocotyle sulamericana n. sp. is described from the gills of Dasyatis guttata
      (Bloch & Schneider) caught off the coast of Brazil near Rio de Janeiro. This
      species can be distinguished from all other members of Heterocotyle Scott, 1904
      by a combination of the morphology of the male copulatory organ, which is a
      short, slightly curved, sclerotised tube with no accessory piece, and the haptor,
      which has a single ridge surmounting all septa. This is the first Heterocotyle
      species to be described from the southwestern Atlantic.

PMID- 22139011
TI  - Collarinema eutriglae n. sp. (Nematoda: Cystidicolidae), a new gastric parasite
      of the scorpaeniform fish Eutrigla gurnardus (Osteichthyes: Triglidae) in the
      North Sea, with remarks on the systematic status of Collarinema Sey, 1970.
AB  - A new species of parasitic nematode, Collarinema eutriglae n. sp.
      (Cystidicolidae), is described from the stomach of the marine scorpaeniform fish
      Eutrigla gurnardus (Linnaeus), the grey gurnard (Triglidae), collected in the
      North Sea in the vicinity of the Shetland Islands (61 degrees 12'N, 00 degrees
      30'E) during March, 2011. The new species, studied using both light and scanning
      electron microscopy, is characterised mainly by the structure of the mouth (small
      pseudolabia with terminal projections, submedian labia and well-developed
      sublabia not exceeding the labia externally), very small simple deirids, the
      length of the spicules (405-423 and 117-135 MUm) and non-filamented eggs.
      Collarinema Sey, 1970 is considered a valid genus and an amended diagnosis is
      provided. Ascarophis collaris Petter, 1970 is transferred to Collarinema as C.
      collaris (Petter, 1970) n. comb.

PMID- 22139012
TI  - Mispaired rNMPs in DNA are mutagenic and are targets of mismatch repair and
      RNases H.
AB  - Numerous studies have shown that ribonucleoside monophosphates (rNMPs) are
      probably abundant among all nonstandard nucleotides occurring in genomic DNA.
      Therefore, it is important to understand to what extent rNMPs may alter genome
      integrity and what factors affect their stability. We developed oligonucleotide
      driven gene correction assays in Escherichia coli and Saccharomyces cerevisiae to
      show that mispaired rNMPs embedded into genomic DNA, if not removed, serve as
      templates for DNA synthesis and produce a genetic change. We discovered that
      isolated mispaired rNMPs in chromosomal DNA are removed by the mismatch repair
      system in competition with RNase H type 2. However, a mismatch within an RNA-DNA
      heteroduplex region requires RNase H type 1 for removal. In the absence of
      mismatch repair and RNases H, ribonucleotide-driven gene modification increased
      by a factor of 47 in yeast and 77,000 in E. coli.

PMID- 22139013
TI  - A unique H2A histone variant occupies the transcriptional start site of active
      genes.
AB  - Transcriptional activation is controlled by chromatin, which needs to be unfolded
      and remodeled to ensure access to the transcription start site (TSS). However,
      the mechanisms that yield such an 'open' chromatin structure, and how these
      processes are coordinately regulated during differentiation, are poorly
      understood. We identify the mouse (Mus musculus) H2A histone variant H2A.Lap1 as
      a previously undescribed component of the TSS of active genes expressed during
      specific stages of spermatogenesis. This unique chromatin landscape also includes
      a second histone variant, H2A.Z. In the later stages of round spermatid
      development, H2A.Lap1 dynamically loads onto the inactive X chromosome, enabling
      the transcriptional activation of previously repressed genes. Mechanistically, we
      show that H2A.Lap1 imparts unique unfolding properties to chromatin. We therefore
      propose that H2A.Lap1 coordinately regulates gene expression by directly opening
      the chromatin structure of the TSS at genes regulated during spermatogenesis.

PMID- 22139014
TI  - Ndc10 is a platform for inner kinetochore assembly in budding yeast.
AB  - Kinetochores link centromeric DNA to spindle microtubules and ensure faithful
      chromosome segregation during mitosis. In point-centromere yeasts, the CBF3
      complex Skp1-Ctf13-(Cep3)(2)-(Ndc10)(2) recognizes a conserved centromeric DNA
      element through contacts made by Cep3 and Ndc10. We describe here the five-domain
      organization of Kluyveromyces lactis Ndc10 and the structure at 2.8 A resolution
      of domains I-II (residues 1-402) bound to DNA. The structure resembles tyrosine
      DNA recombinases, although it lacks both endonuclease and ligase activities.
      Structural and biochemical data demonstrate that each subunit of the Ndc10 dimer
      binds a separate fragment of DNA, suggesting that Ndc10 stabilizes a DNA loop at
      the centromere. We describe in vitro association experiments showing that
      specific domains of Ndc10 interact with each of the known inner-kinetochore
      proteins or protein complexes in budding yeast. We propose that Ndc10 provides a
      central platform for inner-kinetochore assembly.

PMID- 22139015
TI  - RAD51- and MRE11-dependent reassembly of uncoupled CMG helicase complex at
      collapsed replication forks.
AB  - In higher eukaryotes, the dynamics of replisome components during fork collapse
      and restart are poorly understood. Here we have reconstituted replication fork
      collapse and restart by inducing single-strand DNA lesions that create a double
      strand break in one of the replicated sister chromatids after fork passage. We
      found that, upon fork collapse, the active CDC45-MCM-GINS (CMG) helicase complex
      loses its GINS subunit. A functional replisome is restored by the reloading of
      GINS and polymerase E onto DNA in a fashion that is dependent on RAD51 and MRE11
      but independent of replication origin assembly and firing. PCNA mutant alleles
      defective in break-induced replication (BIR) are unable to support restoration of
      replisome integrity. These results show that, in higher eukaryotes, replisomes
      are partially dismantled after fork collapse and fully re-established by a
      recombination-mediated process.

PMID- 22139017
TI  - Expression and characterization of human proinsulin fused to thioredoxin in
      Escherichia coli.
AB  - Native proinsulin (PI) belongs to the class of the difficult-to-express proteins
      in Escherichia coli. Problems mainly arise due to its high proteolytic decay and
      troubles to reproduce the native disulphide pattern. In the present study, human
      PI was produced in E. coli as a fusion thioredoxin protein (Trx-PI). Such
      chimeric protein was obtained from the intracellular soluble fraction, and it was
      purified in one step by affinity chromatography on immobilized phenylarsine
      oxide. Trx-PI was also recovered from inclusion bodies and purified by anion
      exchange chromatography. The product identity and integrity were verified by mass
      analysis (22,173.5 Da) and mapping with Staphylococcus aureus V8 protease. Native
      PI folding was evaluated by biochemical and also by immunochemical analysis using
      specific sera from PI antibody-positive diabetic patients that recognise
      conformational discontinue epitopes. Dose-response curves showed identity between
      standard PI and Trx-PI. Moreover, surface plasmon resonance technique verified
      the correct conformation of the recombinant protein. The biochemical and
      immunochemical assays demonstrated the integrity of the chimera and the epitopes
      involved in the interaction with antibodies. In conclusion, it was possible to
      obtain with high-yield purified human PI as a fusion protein in E. coli and
      useful for analytical purposes.

PMID- 22139018
TI  - Physiology, biochemistry and possible applications of microbial caffeine
      degradation.
AB  - Caffeine, a purine alkaloid is a constituent of widely consumed beverages. The
      scientific evidence which has proved the harm of this alkaloid has paved the way
      for innumerable research in the area of caffeine degradation. In addition to
      this, the fact that the by-products of the coffee and tea industry pollute the
      environment has called for the need of decaffeinating coffee and tea industry's
      by-products. Though physical and chemical methods for decaffeination are
      available, the lack of specificity for removal of caffeine in these techniques
      and their non-eco-friendly nature has opened the area of microbial and enzymatic
      degradation of caffeine. Another important application of microbial caffeine
      degradation apart from its advantages like specificity, eco-friendliness and cost
      effectiveness is the fact that this process will enable the production of
      industrially and medically useful components of the caffeine degradation pathway
      like theobromine and theophylline. This is a comprehensive review which mainly
      focuses on caffeine degradation, large-scale degradation of the same and its
      applications in the industrial world.

PMID- 22139016
TI  - X-chromosome hyperactivation in mammals via nonlinear relationships between
      chromatin states and transcription.
AB  - Dosage compensation in mammals occurs at two levels. In addition to balancing X
      chromosome dosage between males and females via X inactivation, mammals also
      balance dosage of Xs and autosomes. It has been proposed that X-autosome
      equalization occurs by upregulation of Xa (active X). To investigate mechanism,
      we perform allele-specific ChIP-seq for chromatin epitopes and analyze RNA-seq
      data. The hypertranscribed Xa demonstrates enrichment of active chromatin marks
      relative to autosomes. We derive predictive models for relationships among Pol II
      occupancy, active mark densities and gene expression, and we suggest that Xa
      upregulation involves increased transcription initiation and elongation.
      Enrichment of active marks on Xa does not scale proportionally with transcription
      output, a disparity explained by nonlinear quantitative dependencies among active
      histone marks, Pol II occupancy and transcription. Notably, the trend of
      nonlinear upregulation also occurs on autosomes. Thus, Xa upregulation involves
      combined increases of active histone marks and Pol II occupancy, without invoking
      X-specific dependencies between chromatin states and transcription.

PMID- 22139019
TI  - Very low viral load (VLVL) relapse following treatment of naive patients with
      chronic hepatitis C.
AB  - BACKGROUND: Sustained virologic response (SVR) to treatment of naive patients
      with chronic hepatitis C (HCV) with pegylated interferon and ribavirin is 50-60%.
      Patients who relapse have a poor response to re-treatment. We report a group of
      relapse patients with SVR to low-dose re-treatment after 6 months. AIM:
      Characterization of HCV relapse patients with very low viral load (VLVL) (HCV RNA
      <5,000 IU/ml) 6 months after stopping full-dose initial treatment. METHODS: We
      identified 120 consecutive naive patients over 4 years treated with pegylated
      interferon alpha-2a and ribavirin with full-dose therapy for 24 weeks (non
      genotype 1) or 48 weeks (genotype 1) with baseline liver biopsy and at least 6
      months of follow-up after treatment. HCV RNA by PCR and hepatic blood tests were
      obtained monthly during treatment and at least 1, 3, and 6 months post treatment.
      RESULTS: Of the initially treated patients, 54.2% had SVR, 25% non-response and
      20.8% relapsed. Four of 25 who relapsed (16%) and one similar patient referred to
      our program had HCV RNA <5,000 IU/ml 6 months after stopping treatment (VLVL
      relapse). Significant differences (P < 0.05) compared with the 21 other relapse
      patients included all five patients who were genotype 1; 4/5 had cirrhosis,
      baseline HCV RNA was lower, and all had SVR to less intensive re-treatment for 6
      months. CONCLUSION: VLVL relapse patients should be sought, because SVR to re
      treatment is common despite genotype 1 cirrhosis.

PMID- 22139021
TI  - Factors associated with program utilization of radiation therapy treatment for
      VHA and medicare dually enrolled patients.
AB  - We examine how distance to a Veterans Health Administration (VHA) facility,
      patient hometown classification (e.g., small rural town), and service-connected
      disability are associated with veterans' utilization of radiation therapy
      services across the VHA and Medicare. In 2008, 45,914 dually-enrolled veteran
      patients received radiation therapy. Over 3-quarters (35,513) of the patients
      received radiation therapy from the Medicare program. Younger age, male gender,
      shorter distance to a VHA facility, and VHA priority or disability status
      increased the odds of utilizing the VHA. However, veterans residing in urban
      areas were less likely to utilize the VHA. Urban dwelling patients' utilization
      of Medicare instead of the VHA suggests a complex decision that incorporates
      geographic access to VHA services, financial implications of veteran priority
      status, and the potential availability of multiple sources of radiation therapy
      in competitive urban markets.

PMID- 22139023
TI  - Gaze behaviour during space perception and spatial decision making.
AB  - A series of four experiments investigating gaze behavior and decision making in
      the context of wayfinding is reported. Participants were presented with
      screenshots of choice points taken in large virtual environments. Each screenshot
      depicted alternative path options. In Experiment 1, participants had to decide
      between them to find an object hidden in the environment. In Experiment 2,
      participants were first informed about which path option to take as if following
      a guided route. Subsequently, they were presented with the same images in random
      order and had to indicate which path option they chose during initial exposure.
      In Experiment 1, we demonstrate (1) that participants have a tendency to choose
      the path option that featured the longer line of sight, and (2) a robust gaze
      bias towards the eventually chosen path option. In Experiment 2, systematic
      differences in gaze behavior towards the alternative path options between
      encoding and decoding were observed. Based on data from Experiments 1 and 2 and
      two control experiments ensuring that fixation patterns were specific to the
      spatial tasks, we develop a tentative model of gaze behavior during wayfinding
      decision making suggesting that particular attention was paid to image areas
      depicting changes in the local geometry of the environments such as corners,
      openings, and occlusions. Together, the results suggest that gaze during a
      wayfinding tasks is directed toward, and can be predicted by, a subset of
      environmental features and that gaze bias effects are a general phenomenon of
      visual decision making.

PMID- 22139022
TI  - Neural representations of faces and limbs neighbor in human high-level visual
      cortex: evidence for a new organization principle.
AB  - Neurophysiology and optical imaging studies in monkeys and functional magnetic
      resonance imaging (fMRI) studies in both monkeys and humans have localized
      clustered neural responses in inferotemporal cortex selective for images of
      biologically relevant categories, such as faces and limbs. Using higher
      resolution (1.5 mm voxels) fMRI scanning methods than past studies (3-5 mm
      voxels), we recently reported a network of multiple face- and limb-selective
      regions that neighbor one another in human ventral temporal cortex (Weiner and
      Grill-Spector, Neuroimage, 52(4):1559-1573, 2010) and lateral occipitotemporal
      cortex (Weiner and Grill-Spector, Neuroimage, 56(4):2183-2199, 2011). Here, we
      expand on three basic organization principles of high-level visual cortex
      revealed by these findings: (1) consistency in the anatomical location of
      functional regions, (2) preserved spatial relationship among functional regions,
      and (3) a topographic organization of face- and limb-selective regions in
      adjacent and alternating clusters. We highlight the implications of this
      structure in comparing functional brain organization between typical and atypical
      populations. We conclude with a new model of high-level visual cortex consisting
      of ventral, lateral, and dorsal components, where multimodal processing related
      to vision, action, haptics, and language converges in the lateral pathway.

PMID- 22139024
TI  - TGF-beta1 induces peritoneal fibrosis by activating the Smad2 pathway in
      mesothelial cells and promotes peritoneal carcinomatosis.
AB  - Peritoneal dissemination is one of the main causes of death in gastric cancer
      patients. Our previous study demonstrated that peritoneal fibrosis induced by
      transforming growth factor-beta1 (TGF-beta1) may provide a favorable environment
      for the dissemination of gastric cancer. The role of Smad3 in the development of
      dermal fibrosis, subcapsular cataract, and peritoneal fibrosis has been reported.
      However, the potential role of Smad2 in the development of fibrosis is unclear.
      The objective of this study was to determine the effect of Smad2 in peritoneal
      fibrosis, induced by TGF-beta1, on dissemination of gastric cancer. Here we
      demonstrate that TGF-beta1 significantly stimulated the expression of collagen
      III and fibronectin in mesothelial cells through the Smad2 signal transduction
      pathway, but knockdown of the Smad2 gene by silencing siRNA partially inhibited
      these effects. This inhibition was associated with a depressed adhesion and
      invasiveness of gastric cancer cells. We conclude that peritoneal fibrosis
      induced by TGF-beta1 is dependent on Smad2 signaling and may provide a hospitable
      environment for carcinomatosis.

PMID- 22139026
TI  - Compression anastomoses in colon and rectal surgery with the NiTi ColonRingTM.
AB  - BACKGROUND: The aim of this prospective study was to evaluate safety and efficacy
      of the NiTi ColonRingTM for anastomoses on the colon or rectum. METHODS: During
      the period September 2008-June 2011, anastomosis using the NiTi ColonRingTM was
      scheduled to be performed on 60 patients (36 females, 24 males/mean aged 67
      years), 53 of whom underwent colectomy for cancer and 7 reconstruction after
      Hartmann's procedure. Application of the device failed in one case due to
      anatomical reasons. Colorectal resections performed were as follows: Right
      hemicolectomy (5 patients), left colectomy (2), sigmoidectomy (15) and low
      anterior resection (31). A follow-up clinic visit after 1 month was planned for
      all patients. Ten patients among the first 14 had rectosigmoidoscopy at 2-3
      months. All cancer patients were scheduled for colonoscopy at 12 months. RESULTS:
      No intraoperative or postoperative bleeding related to the anastomotic technique
      was recorded. Median hospital stay after surgery was 10.2 days (9-22 days). One
      patient died on day 13 due to myocardial infarction. Clinically apparent leak was
      detected in one patient who had undergone reconstruction after Hartmann; the only
      treatment required was total parenteral nutrition for 12 days. Anastomotic
      stenosis occurred in another one patient who had undergone reconstruction after
      Hartmann; it was easily resolved by balloon dilatation. Mild complications were
      encountered in 23 other patients (39%). Oral feeding started after day 4.
      Anastomotic rings were expelled naturally within 7-17 days (mean, 9.2 days). A
      satisfactory anastomosis was revealed in patients examined colonoscopically at 2
      3 and 12 months. Mean follow-up was 15.2 months (2-33 months). CONCLUSIONS: NiTi
      ColonRingTM is reliable, safe and efficacious for large bowel anastomoses.

PMID- 22139027
TI  - The relationship between D-dimer level and the development of atrial fibrillation
      in patients with systolic heart failure.
AB  - Heart failure (HF) is one of the most common and leading cause of death
      worldwide. Clinical trials provide evidence that the development of atrial
      fibrillation (AF) is a marker of poor prognosis in patients with HF. Furthermore,
      elevated D-dimer level is associated with increased cardiovascular mortality
      independent of AF in HF patients. We investigated whether plasma D-dimer levels
      in patients with hospitalized systolic HF could predict development of AF. A
      total of 150 consecutive patients with sinus rhythm who admitted to the emergency
      department with hospitalized systolic HF were evaluated. All hospitalized
      patients were obtained D-dimer levels within the first 24 h following admission.
      Atrial fibrillation developed in 31 (20.7%) patients during follow-up period of
      6.3 +/- 5 months. Patients who developed atrial fibrillation had significantly
      increased levels of D-dimer [608 (339-1,022) ng/ml versus 1,100 (608-2,599)
      ng/ml, P = 0.001]. Optimal cut-off level of D-dimer to predict development of AF
      was found to be >792 ng/ml. D-dimer >792 ng/ml, right ventricular dilatation,
      age, systolic pulmonary pressure, left atrium size, moderate to severe tricuspid
      regurgitation, and beta blocker usage were found to have prognostic significance
      in univariate analysis. In multivariate Cox proportional-hazards model, D-dimer
      levels >792 ng/ml (HR = 3.019, P = 0.006), and right ventricular dilatation (HR =
      8.676, P = 0.003) were associated with an increased risk of new-onset AF. In
      conclusion, D-dimer could predict development of AF in patients with hospitalized
      systolic HF.

PMID- 22139029
TI  - Better functional outcome provided by short-armed sigmoid colon-rectal side-to
      end anastomosis after laparoscopic low anterior resection: a match-paired
      retrospective study from China.
AB  - PURPOSE: Side-to-end anastomosis using the descending colon has been proved to be
      as effective as J pouch in alleviating low anterior resection syndrome. However,
      using the sigmoid colon, which is less compliant for reconstruction after rectal
      cancer surgery, is common in China due to less prevalence of diverticulosis. The
      effectiveness of using the sigmoid colon for a side-to-end colorectal anastomosis
      in improving bowel dysfunction after laparoscopic low anterior resection of
      rectal cancer has not been investigated. This study was designed to compare the
      functional and surgical outcomes between the two anastomoses. METHODS: From
      October 2007 to December 2008, 16 rectal cancer patients underwent laparoscopic
      low anterior resection with short-armed (length of side limb 2-4 cm) side-to-end
      sigmoidorectal anastomosis at our department. The bowel functional results of
      these patients at 6 months and 1 year postoperatively were recorded and compared
      with that of another 1:2 matched 30 patients undergoing straight anastomosis.
      RESULTS: Bowel movement frequency in the side-to-end group was obviously less
      than that in the straight group 6 months postoperatively. Patients in the side-to
      end group also had an improved incontinence score, a better ability to defer
      defecation, and less repeated evacuation. No differences were found between two
      groups 1 year after surgery. CONCLUSION: The study shows that the short-armed
      side-to-end colorectal anastomosis using the sigmoid colon can also improve the
      short-term bowel function in patients undergoing laparoscopic low anterior
      resection.

PMID- 22139028
TI  - Nerve growth factor induces cord formation of mesenchymal stem cell by promoting
      proliferation and activating the PI3K/Akt signaling pathway.
AB  - AIM: To investigate whether nerve growth factor (NGF) induced angiogenesis of
      bone marrow mesenchymal stem cells (MSCs) and the underlying mechanisms. METHODS:
      Bone marrow MSCs were isolated from femors or tibias of Sprague-Dawley rat, and
      cultured. The cells were purified after 3 to 5 passages, seeded on Matrigel
      coated 24-well plates and treated with NGF. Tube formation was observed 24 h
      later. Tropomyosin-related kinase A (TrkA) and p75NTR gene expression was
      examined using PCR analysis and flow cytometry. Growth curves were determined via
      cell counting. Expression of VEGF and pAkt/Akt were analyzed with Western blot.
      RESULTS: NGF (25, 50, 100 and 200 MUg/L) promoted tube formation of MSCs. The
      tubular length reached the maximum of a 2.24-fold increase, when the cells were
      treated with NGF (50 MUg/L). NGF (50 MUg/L) significantly enhanced Akt
      phosphorylation. Pretreatment with the specific PI3K inhibitor LY294002 (10
      MUmol/L) blocked NGF-stimulated Akt phosphorylation, tube formation and
      angiogenesis. NGF (25-200 MUg/L) did not affect the expression of TrkA and
      vascular endothelial growth factor (VEGF), but significantly suppressed the
      expression of p75NTR. NGF (50 MUg/L) markedly increased the proliferation of
      MSCs. CONCLUSION: NGF promoted proliferation of MSCs and activated the PI3K/Akt
      signaling pathway, which may be responsible for NGF induction of MSC
      angiogenesis.

PMID- 22139030
TI  - Impact of preoperative targeted therapy on postoperative complications after
      resection of colorectal liver metastases.
AB  - PURPOSE: The impact of chemotherapy (CTx) on morbidity after liver resection for
      colorectal metastases (CRC-LM) has been increasingly investigated during recent
      years. Biologic agents like bevacizumab (BEV) or cetuximab (CET) are now added as
      "targeted therapy" (TT), also in neoadjuvant settings. Initial series could
      demonstrate the safety of those regimens in liver resection but data are still
      scarce. We evaluated the impact of CTx with BEV or CET (CTx + TT) on
      perioperative morbidity and mortality. METHODS: Two hundred thirty-seven patients
      who underwent liver resections for CRC-LM after chemotherapy before surgery since
      1999 were included. One hundred eighty-five patients (78%) had preoperative CTx
      regimen without biologic agents (fluoropyrimidine-, oxaliplatin-, or irinotecan
      based) and 52 (22%) had CTx + TT (39 BEV, 11 CET, 2 CET/BEV). After preoperative
      CTx + TT, a time interval of at least 4-6 weeks and a residual liver volume of
      >35% before surgery were required. RESULTS: Hemihepatectomy or more was performed
      in about half of the patients. The median amount of intraoperatively transfused
      blood was 0 ml in both groups (p = 0.34). Overall mortality was 1.7% and slightly
      elevated in patients with CTx + TT (3.8% vs. 1.1%, p = 0.17). Any complication
      occurred in (CTx + TT vs. CTx) 52% and 46%, respectively (p = 0.47). The rates of
      liver failure (9.6% vs. 9.7%, p = 0.98), infectious complications such as wound
      infection (19% vs. 16%, p = 0.62) and abdominal abscess (8% vs. 6.5%, p = 0.71),
      as well as the rate of relaparotomies (11.5% vs. 7.0%, p = 0.29) showed no
      significant differences between the groups with TT or without. In multivariate
      analyses, neither type nor duration of CTx nor the time interval between CTx and
      surgery showed any influence on complication rates. CONCLUSIONS: Our data confirm
      the safety of targeted therapy before liver resection for CRC-LM. This effect may
      in part be due to our treatment policy (time interval to resection and residual
      liver volume) after intensive preoperative CTx.

PMID- 22139031
TI  - The detection of surface patterns by flexible spectral imaging color enhancement
      without magnification for diagnosis of colorectal polyps.
AB  - PURPOSE: Flexible spectral imaging color enhancement (FICE), or image-enhanced
      endoscopy, can enhance visualization of surface and vascular patterns of
      colorectal polyps. Resolution of FICE has recently been improved. We evaluated
      diagnostic accuracy for neoplastic and non-neoplastic colorectal polyp
      differentiation with detection of surface patterns by FICE without magnification.
      METHODS: Retrospective analysis of 151 colorectal polyps evaluated by FICE
      without magnification was performed. Neoplastic surface patterns were defined as
      tubular and oval pit. We aimed to determine sensitivity, specificity, positive
      and negative predictive values (PPV and NPV), and accuracy in correlating
      diagnosis by FICE without magnification with histology. Moreover, findings were
      compared to those of white-light endoscopy (WL) and chromoendoscopy (CHR).
      RESULTS: Of the 151 colorectal polyps, 95 were identified as neoplastic and 56
      were identified as non-neoplastic. FICE without magnification had a sensitivity
      of 89.4%, specificity of 89.2%, PPV of 93.4%, NPV of 83.3%, and accuracy of
      89.4%. The accuracy of FICE value was higher than that of WL (sensitivity of
      74.7%, specificity of 73.2%, PPV of 82.5%, NPV of 63.0%, and accuracy of 74.1%)
      and was worse than that of CHR (sensitivity of 96.8%, specificity of 89.2%, PPV
      of 93.9%, NPV of 96.1%, and accuracy of 94.7%). Imaging evaluation was validated
      by inter-/intra-observer measurements, demonstrating consistent results.
      CONCLUSIONS: The detection of surface patterns by FICE without magnification is
      useful for differential diagnosis of colorectal polyps. We believe that FICE
      without magnification is more convenient and easier method than CHR.

PMID- 22139033
TI  - Endoscopic transluminal abscess drainage for Hinchey II colonic diverticulitis.

PMID- 22139032
TI  - The predictive value of single nucleotide polymorphisms in the VEGF system to the
      efficacy of first-line treatment with bevacizumab plus chemotherapy in patients
      with metastatic colorectal cancer: results from the Nordic ACT trial.
AB  - PURPOSE: Bevacizumab and chemotherapy is a common choice for first-line treatment
      of metastatic colorectal cancer (mCRC). So far, no predictive markers have been
      identified. The aim was to investigate the possible predictive value of single
      nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF)
      system in this setting. METHODS: Pre-treatment blood samples and response
      evaluations were available from 218 of the 249 included patients. All patients
      received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or
      capecitabine combined with either oxaliplatin (FOLFOX or XELOX, n = 183) or
      irinotecan (FOLFIRI or XELIRI, n = 66). Germline DNA was isolated from whole
      blood, and five SNPs in the VEGF-A gene, one SNP in the VEGF receptor 1 (VEGFR-1)
      gene and three SNPs in the VEGFR-2 gene were analysed by polymerase chain
      reaction. Response was evaluated according to RECIST version 1.0, and the
      association to genotypes was analysed using Fisher's exact test. RESULTS: The
      VEGFR-1 319 C/A SNP was significantly associated with response. Objective
      response was observed in 36% of the patients with CC genotype, 40% with CA and
      56% with AA, p = 0.048. The response rates also differed significantly between
      patients with C-allele containing genotypes (CC + CA) (39%) and patients
      homozygous for the A-allele (AA) (56%), p = 0.015. There was no correlation
      between response rates and the remaining SNPs. CONCLUSIONS: The VEGFR-1 319 C/A
      SNP is a potential predictive marker for bevacizumab plus chemotherapy in
      patients with mCRC. Patients with the A allele appeared to have increased
      response rates. The results call for validation.

PMID- 22139034
TI  - Arsenic contamination and speciation in surrounding waters of three old cinnabar
      mines.
AB  - The impact of arsenic pollution in waters from the surroundings of three
      abandoned Hg mines in Northern Spain, as well as reaching the Caudal River, was
      evaluated. For assessing the factors controlling arsenic release, an extensive
      study based on the physicochemical characterization and multivariate statistical
      analysis of waters upstream and downstream each mine site was performed. Waters
      downstream of the La Soterrana mine present the highest arsenic concentrations,
      up to 38.8 mg L(-1), coming mainly from the solubilisation of calcium, magnesium
      and strontium arsenates at a pH close to neutral. Although arsenic concentrations
      downstream of La Pena are markedly lower, these values remain too high,
      indicating that the encapsulation carried out in this spoil heap is insufficient.
      In addition, the high water flow in this point involves an extremely high input
      of arsenic to the surroundings (0.3 g s(-1)). Waters close to tailings from Los
      Rueldos suffer from acid mine drainage, provoking an important solubilisation of
      arsenic and heavy metals, a situation which is rapidly softened with distance.
      The study of arsenic speciation reveals the omnipresence of As(v) in waters from
      the three mines, whereas in La Pena low amounts of As(iii) were also detected.
      Different preservation methods for As speciation were compared, such as the
      addition of HCl, EDTA and the storage of samples without any additive, and no
      alteration of samples in any case up to nine months after the collection was
      observed. A study of seasonal variations of As and the main parameters affecting
      its concentration and speciation was completed throughout a year, showing no
      remarkable dependency with rainfall for any studied variable.

PMID- 22139035
TI  - Marking the occasion.

PMID- 22139025
TI  - [Rhinosinusitis guidelines--unabridged version: S2 guidelines from the German
      Society of Otorhinolaryngology, Head and Neck Surgery].

PMID- 22139036
TI  - Celebrating structural biology.

PMID- 22139037
TI  - Prospects for an HIV vaccine: leading B cells down the right path.

PMID- 22139042
TI  - Effects of different replicons in conjugative plasmids on transformation
      efficiency, plasmid stability, gene expression and n-butanol biosynthesis in
      Clostridium tyrobutyricum.
AB  - Clostridium tyrobutyricum ATCC 25755 can produce butyric acid, acetic acid, and
      hydrogen as the main products from various carbon sources. In this study, C.
      tyrobutyricum was used as a host to produce n-butanol by expressing adhE2 gene
      under the control of a native thiolase promoter using four different conjugative
      plasmids (pMTL82151, 83151, 84151, and 85151) each with a different replicon
      (pBP1 from C. botulinum NCTC2916, pCB102 from C. butyricum, pCD6 from Clostridium
      difficile, and pIM13 from Bacillus subtilis). The effects of different replicons
      on transformation efficiency, plasmid stability, adhE2 expression and
      aldehyde/alcohol dehydrogenase activities, and butanol production by different
      mutants of C. tyrobutyricum were investigated. Among the four plasmids and
      replicons studied, pMTL82151 with pBP1 gave the highest transformation
      efficiency, plasmid stability, gene expression, and butanol biosynthesis. Butanol
      production from various substrates, including glucose, xylose, mannose, and
      mannitol were then investigated with the best mutant strain harboring adhE2 in
      pMTL82151. A high butanol titer of 20.5 g/L with 0.33 g/g yield and 0.32 g/L h
      productivity was obtained with mannitol as the substrate in batch fermentation
      with pH controlled at ~6.0.

PMID- 22139043
TI  - Error-provoking conditions in the medication use process: the case of a
      government hospital in Ghana.
AB  - OBJECTIVE: This study aimed to explore error-provoking factors prevalent in
      hospitals that have the potential to cause medication errors and to create
      awareness of the existence of medication errors. METHODS: A total of 200 medical
      folders of in-patients in the health facility were randomly selected and assessed
      based on a checklist to record potential medication errors. The medication use
      process and working environment as well as drug packages and labels in the
      pharmacy were observed, and potential medication errors were documented.
      FINDINGS: Of the 162 valid in-patient folders studied, 60.5% of the patients did
      not receive the actual quantity of drugs they were supposed to. Illegible
      handwriting on medication orders and prescription were common observations in the
      folders studied. Look-alike medicine packages and labeling were found. The
      working space in the dispensary was congested, and distractions (e.g., ringing
      personal telephones, being called from one task to attend to another, and
      unnecessary conversation between personnel) were common. CONCLUSIONS: This study
      has highlighted the vulnerability of the medication use process in the study site
      to medication errors. The findings may just be a tip of the iceberg; therefore,
      the researchers plan undertaking a multicenter study. In the absence of that,
      however, there is a need for a national policy on patient safety, and a national
      policy on incident reporting would help in determining the incidence, types, and
      potential causes of medication errors to improve patient safety.

PMID- 22139044
TI  - Measuring the effectiveness of pharmacology teaching in undergraduate medical
      students.
AB  - OBJECTIVE: Information overload and recent curricular changes are viewed as
      important contributory factors to insufficient pharmacological education of
      medical students. This study was designed to assess the effectiveness of
      pharmacology teaching in our medical school. METHODS: The study subjects were 455
      second-year medical students, class of 2010, and 26 pharmacology teachers at the
      National University of Mexico Medical School. To assess pharmacological
      knowledge, students were required to take 3 multiple-choice exams (70 questions
      each) as part of their evaluation in the pharmacology course. A 30-item
      questionnaire was used to explore the students' opinion on teaching. Pharmacology
      professors evaluated themselves using a similar questionnaire. Students and
      teachers rated each statement on a 5-point Likert scale. RESULTS: The groups'
      exam scores ranged from 54.5% to 90.0% of correct responses, with a mean score of
      77.3%. Only 73 (16%) of 455 students obtained an exam score of 90% and higher.
      Students' evaluations of faculty and professor self-ratings were very high (90%
      and 96.2%, of the maximal response, respectively). Student and professor ratings
      were not correlated with exam scores (r = 0.291). CONCLUSIONS: Our study shows
      that knowledge on pharmacology is incomplete in a large proportion of second-year
      medical students and indicates that there is an urgent need to review
      undergraduate training in pharmacology. The lack of relationship between the
      subjective ratings of teacher effectiveness and objective exam scores suggests
      the use of more demanding measures to assess the effectiveness of teaching.

PMID- 22139045
TI  - Barriers to receiving substance abuse treatment among rural pregnant women in
      Kentucky.
AB  - Research presenting outcomes for women who enter substance abuse treatment during
      pregnancy consistently shows benefits. While treatment has nearly universal
      benefits, there are many barriers to seeking substance abuse treatment for
      pregnant women. The purpose of this study is to explore barriers for rural
      pregnant women seeking substance abuse treatment. There were three eligibility
      criteria for study participation: (1) aged 18 and older, (2) pregnant, and (3)
      undergoing short-term inpatient detoxification at the University of Kentucky
      Chandler Medical Center. Eighty-five rural women (N = 85) were included in the
      analysis. Substance use history and previous treatment were assessed with
      measures adapted from the Addiction Severity Index. Treatment barriers were
      measured with three qualitative questions and were coded into four overarching
      categories: availability, accessibility, affordability, and acceptability
      barriers. This sample had an extensive substance use history. Almost all
      participants had used alcohol (98%), marijuana (98%), illicit opiates (99%), and
      cigarettes (97%). On average, participants reported about two barriers to
      receiving treatment (Mean = 1.8; SD = 1.3), with over 80% of the sample reporting
      having experienced any barrier to treatment. The majority experienced
      acceptability (51%) and accessibility (49%) barriers. Twenty-six percent (26%) of
      the sample reported availability barriers. A smaller percentage of participants
      reported affordability barriers (13%). Rural pregnant women seeking substance
      abuse treatment face many obstacles to receiving needed treatment. More studies
      on barriers to substance abuse treatment among rural pregnant women are needed.
      Identifying these barriers can help in improving treatment access and services.

PMID- 22139046
TI  - Alcohol use patterns among postpartum women.
AB  - While much attention has been paid to women's drinking during pregnancy, few
      studies address a woman's drinking once she has given birth, which presents
      potential dangers to herself and her child. This time of transition can be
      extremely stressful, potentially leading to problem drinking. On the other hand,
      this new role and change in lifestyle may be protective against alcohol use and
      abuse. We used the California Women's Health Survey (CWHS), a randomized sample
      of adult women in California, to compare new mothers' drinking behaviors to other
      women. In order to obtain a large enough sample to observe trends in
      subpopulations, we combined CWHS data from years 1997-2008 (n = 28,537 women aged
      18-48). We used logistic regression to determine the individual-level
      characteristics that best predicted the outcomes postpartum and to compare new
      mothers (those with a child in the household <1 year and pregnant in the last 5
      years) to other women for any alcohol use, heavy episodic drinking and number of
      days of alcohol use. New mothers were significantly less likely to engage in all
      behavior outcomes after adjustment for race/ethnicity, income, employment,
      education, age, and marital status, though new mothers who are not married and
      those in higher income brackets were identified as groups at higher risk of
      drinking. Although new motherhood could prove to be a risk factor for some women,
      we found that being a new mother is protective against all measures of drinking.

PMID- 22139048
TI  - The prevalence of chronic kidney disease in a Flemish primary care morbidity
      register.

PMID- 22139047
TI  - Parental weight (mis)perceptions: factors influencing parents' ability to
      correctly categorise their child's weight status.
AB  - This study investigates parents' ability to correctly classify their child's
      weight status. The influence of parent and child socio-demographic and lifestyle
      factors on parental misclassification of their child's weight status is explored.
      A representative sample of Irish children (aged 5-12 (n = 596) years, aged 13-17
      years (n = 441)) and their parents (n = 1885) were recruited to participate in a
      national dietary survey. Parental perceptions of their child's weight and their
      own weight were measured. Anthropometric measurements (weight and height) were
      objectively measured for parents and children. Body Mass Index (BMI) scores were
      derived and categorised as normal, overweight or obese using standard references.
      Over 80% of parents of overweight boys and 79.3% of parents of overweight girls
      reported their child's weight was fine for his/her height and age. Furthermore,
      44.4% of parents of obese boys and 45.3% of parents of obese girls felt their
      child's weight was fine for their height and age. Parents were significantly less
      likely to be correct about their sons' weight status and more likely to be
      correct the older the child. Parents were over 86% less likely to be correct
      about their child's weight if their child was overweight and approximately 59%
      less likely to be correct if the child was obese, compared to parents of normal
      weight children. This research suggests that parents are failing to recognise
      overweight and obesity in their children with factors such as parental weight
      status, child's age and gender influencing this.

PMID- 22139049
TI  - A short, intensive cognitive behavioral pain management program reduces health
      care use in patients with chronic low back pain: two-year follow-up results of a
      prospective cohort.
AB  - PURPOSE: Cognitive behavioral interventions are recommended as non-invasive
      treatment options for patients with chronic low back pain (CLBP). However, most
      treatment effects are small and short-lived. Although a 2-week intensive pain
      management program for patients with CLBP seems to be effective, the long-term
      results are not known. The purpose of this study is to evaluate the stability of
      the 2-year follow-up results and whether this is reflected in the use of health
      care services. METHODS: A prospective cohort study was performed. Pre-treatment
      characteristics of patients and data of outcomes obtained at 1-year follow-up
      were used. At 2-year follow-up a structured interview was conducted following the
      principles of a post-marketing survey. Outcomes included daily functioning,
      quality of life, current intensity of pain, disturbance of pain during daily
      activities, and indicators of the use of pain medication and health-care
      services. RESULTS: Of the 90 eligible patients 85 (94%) participated in the post
      marketing survey. The 1-year clinical relevant effects are maintained at 2-year
      follow-up. Effect sizes for functioning and quality of life were large. More than
      65% reached preset minimal clinically important differences. At pre-treatment all
      patients consulted their general practitioner (GP) and medical specialist (MS).
      At 2-year follow-up 73% reported having consulted neither a GP nor an MS during
      the previous year. Most of the patients indicated not to use any pain medication
      (57%) and the percentage patients using opioids have decreased (14%). Moreover,
      81% reported to be at work. CONCLUSIONS: The gained results from selected and
      motivated patients with longstanding CLBP at 1-year follow-up are stable at 2
      year follow-up. Above all, most of the participants are at work and results
      indicate that the use of both pain medication and health care have decreased
      substantially.

PMID- 22139050
TI  - The efficacy of porous hydroxyapatite bone chip as an extender of local bone
      graft in posterior lumbar interbody fusion.
AB  - OBJECTIVE: To evaluate whether a synthetic bone chip made of porous
      hydroxyapatite can effectively extend local decompressed bone graft in
      instrumented posterior lumbar interbody fusion (PLIF). METHODS: 130 patients, 165
      segments, who had undergone PLIF with cages and instrumentation for single or
      double level due to degenerative conditions, were investigated retrospectively by
      independent blinded observer. According to the material of graft, patients were
      divided into three groups. HA group (19 patients, 25 segments): with
      hydroxyapatite bone chip in addition to autologous local decompressed bone, IBG
      group (25 patients, 28 segments): with autologous iliac crest bone graft in
      addition to local decompressed bone and LB group (86 patients, 112 segments):
      with local decompressed bone only. Radiologic and clinical outcome were compared
      among groups and postoperative complications, transfusion, time and cost of
      operation and duration of hospitalization were also investigated. RESULTS:
      Radiologic fusion rate and clinical outcome were not different. Economic cost,
      transfusion and hospital stay were also similar. But operation time was
      significantly longer in IBG group than in other groups. There were no lasting
      complications associated with HA and LB group with contrast to five cases with
      persisting donor site pain in IBG group. CONCLUSION: Porous hydroxyapatite bone
      chip is a useful bone graft extender in PLIF when used in conjunction with local
      decompressed bone.

PMID- 22139051
TI  - Malignant peripheral nerve sheath tumours of the spine: clinical manifestations,
      classification, treatment, and prognostic factors.
AB  - BACKGROUND AND OBJECTIVES: To summarise our experience treating patients with
      spinal malignant peripheral nerve sheath tumours (MPNSTs). METHODS: We
      retrospectively reviewed the records of patients diagnosed with spinal MPNSTs who
      received surgical treatment from January 1998 to December 2009. RESULTS:
      Postoperative follow-up data were available for 14/16 patients with spinal MPNSTs
      (7 men, 7 women; median age = 44 years [range: 23-68 years]). Eight of 14 (57.1%)
      patients had primary and 6/14 (42.9%) recurrent MPNSTs. A total of 12/14 (85.7%)
      patients underwent total tumour resection, whereas 2/14 (14.3%) patients
      underwent subtotal tumour resection. Malignancies were graded low in 4 (28.6%)
      and high in 10 (71.1%) cases. A total of 12/14 (85.7%) patients experienced
      tumour recurrence and 10/14 (71.4%) patients died during the course of follow-up.
      The 0.5- 1-, 3-, and 5-year survival rates were 64.3, 48.2, 32.1, and 21.4%,
      respectively. Overall survival was significantly associated with tumour malignant
      degree (P = 0.012). CONCLUSION: Diagnosis of spinal MPNSTs should be made with
      reference to clinical, radiological, and pathological findings. Surgical
      resection is the best available option for treating spinal MPNST; however,
      postoperative prognosis is poor.

PMID- 22139052
TI  - Reproducibility of the cervical range of motion (CROM) device for individuals
      with sub-acute whiplash associated disorders.
AB  - PURPOSE: The objective of this study was to evaluate the reproducibility of the
      cervical range of motion device when measuring both active and passive range of
      motion in a group of individuals with sub-acute Whiplash Associated Disorders
      (WAD). METHODS: Participants were recruited as part of a large multi-centre
      Randomised Controlled Trial from UK emergency departments. Experienced research
      physiotherapists measured active and passive cervical spine movements in all
      directions. Both intra- and inter-observer reliability and agreement were
      assessed using the intra-class correlation coefficient, standard error of
      measurement and limits of agreement methods. RESULTS: Different groups of 39 and
      19 subjects were included in the intra and inter-observer studies, respectively.
      The CROM device demonstrated substantial intra- and inter-observer reliability
      and agreement for all the active and passive half-cycle movements (ICC range 0.82
      0.99) with the exception of one (passive right lateral flexion for inter
      observer; ICC 0.77). CONCLUSIONS: The CROM device has proven to be a reproducible
      measurement method for a symptomatic WAD population using the measurement
      protocol described and can be used with confidence to differentiate individuals
      according to a single measurement.

PMID- 22139053
TI  - Progression of prostate carcinogenesis and dietary methyl donors: temporal
      dependence.
AB  - Insufficient dose of dietary methyl groups are associated with a host of
      conditions ranging from neural tube defects to cancer. On the other hand, it is
      not certain what effect excess dietary methyl groups could have on cancer. This
      is especially true for prostate cancer, a disease that is characterized by
      increasing DNA methylation changes with increasing grade of the cancer. In this
      three-part study in animals, we look at (i) the effect of excess methyl donors on
      the growth rate of prostate cancer in vivo, (ii) the ability of 5-aza-2'
      deoxycytidine (AdC), a demethylating agent, to demethylate in the presence of
      excess dietary methyl donors, and (iii) the effect of in utero feeding of excess
      methyl donors to the later onset of prostate cancer. The results show that when
      mice are fed a dietary excess of methyl donors, we do not see (i) an increase in
      the growth rate of DU-145 and PC-3 xenografts in vivo, or (ii) interference in
      the ability of AdC to demethylate the promoters of androgen receptor or Reprimo
      of prostate cancer xenografts but (iii) a protective effect on the development of
      higher grades of prostate cancer in the "Hi-myc" mouse model of prostate cancer
      which were fed the increased methyl donors in utero. We conclude that the impact
      of dietary methyl donors on prostate cancer progression depends upon the timing
      of exposure to the dietary agents. When fed before the onset of cancer, that is,
      in utero, excess methyl donors can have a protective effect on the progression of
      cancer.

PMID- 22139056
TI  - [Update on traumatic surgery].

PMID- 22139055
TI  - The actions of Shiga toxin-2 administration into the brain on renal sympathetic
      nerve activity.
AB  - BACKGROUND: It remains unclear whether Shiga toxin-2 (Stx-2)-induced acute
      encephalopathy contributes to an inappropriate activation of the renal
      sympathetic outflow. This investigation set out to examine the impact of Stx-2
      administered into the brain on the neural control of the kidney. METHODS: Using
      acutely anaesthetised male Wistar rats (300-350 g), saline, Stx-2 (10 MUg/kg) or
      lipopolysaccharide (LPS 50 MUg/kg) was administered intracerebroventricularly
      (icv) and measurements of renal haemodynamic and excretory function or renal
      nerve activity were made over the following 4 h. RESULTS: There were minimal
      changes in renal blood flow, glomerular filtration rate, urine flow or sodium
      excretion, irrespective of whether saline, Stx-2 or LPS was administered into the
      brain. The renal nerve recordings showed that whereas saline and LPS caused small
      inconsistent changes in renal nerve activity over the 4-h period, there was a
      significant (P < 0.05) doubling of renal nerve activity in the rats which were
      administered Stx-2 icv. Immunocytochemical examination demonstrated that Stx-2
      induced globotriaosylceramide receptors, the proposed functional receptors for
      Stx-2, on the blood vessel walls around the hypothalamus and hippocampus, and
      histological evaluations showed that changes in the kidney were beginning to
      occur to the renal tubular epithelial cells, consistent with developing lesions.
      CONCLUSION: Stx-2 crosses either the blood-brain barrier or the blood
      cerebrospinal fluid barrier where it can alter neuronal function and trigger
      neuronal derangements. These structural changes could contribute, at least in
      part, to the raised renal sympathetic nerve activity.

PMID- 22139054
TI  - Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric
      adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways.
AB  - Gastric cancer is the fourth most commonly diagnosed cancer with the second
      highest mortality rate worldwide. Surgery, chemotherapy and radiation therapy are
      generally used for the treatment of stomach cancer but only limited clinical
      response is shown by these therapies and still no effectual therapy for advanced
      gastric adenocarcinoma patients is available. Therefore, there is a need to
      identify other therapeutic agents against this life-threatening disease. Plants
      are considered as one of the most important sources for the development of
      anticancer drugs. Magnolol, a natural compound possesses anticancer properties.
      However, effects of Magnolol on human gastric cancer remain unexplored. The
      effects of Magnolol on the viability of SGC-7901 cells were determined by the MTT
      assay. Apoptosis, mitochondrial membrane potential and cell cycle were evaluated
      by flow cytometry. Protein expression of Bcl-2, Bax, caspase-3 and PI3K/Akt was
      analysed by Western blotting. Magnolol induced morphological changes in SGC-7901
      cells and its cytotoxic effects were linked with DNA damage, apoptosis and S
      phase arrest in a dose-dependent manner. Magnolol triggered the mitochondrial
      mediated apoptosis pathway as shown by an increased ratio of Bax/Bcl-2,
      dissipation of mitochondrial membrane potential (DeltaPsim), and sequential
      activation of caspase-3 and inhibition of PI3K/Akt. Additionally, Magnolol
      induced autophagy in SGC-7901 cells at high concentration but was not involved in
      cell death. Magnolol-induced apoptosis of SGC-7901 cells involves mitochondria
      and PI3K/Akt-dependent pathways. These findings provide evidence that Magnolol is
      a promising natural compound for the treatment of gastric cancer and may
      represent a candidate for in vivo studies of monotherapies or combination
      antitumor therapies.

PMID- 22139057
TI  - [Proximal humerus fractures].

PMID- 22139058
TI  - [Proximal humerus fracture: is fixed-angle plate osteosynthesis superior to
      conservative treatment?].
AB  - KEYWORDS: Despite the fact that proximal humerus fractures represent one of the
      most frequent types of all fractures, the quality of evidence is poor although it
      has improved in recent years. It is widely agreed in the literature that
      nondisplaced fractures can be treated conservatively with good outcome. Two
      recent prospective randomized studies have shown that this also applies to
      displaced three- and four-part fractures.The results of fixed-angle plate
      osteosynthesis are also not superior to conservative management in complex
      displaced fractures in the elderly and in many aspects are even worse. Fixed
      angle plate osteosynthesis has not fulfilled expectations. High rates of
      complications and revision surgeries as well as moderate functional results have
      been demonstrated in numerous studies.Conventional fracture prostheses or inverse
      prostheses are solutions fo complex not reducible and/or retainable. Also for the
      dislocated 4-part fracture of the patient above 60 ears no general advantages of
      the joint replacement compared to conservative treatment could be shown in a
      recent scandinavian prospective randomized clinical trial.

PMID- 22139059
TI  - [Traumatic rupture of the aorta: origin, diagnosis, and therapy of a life
      threatening aortic injury].
AB  - In polytraumatized patients, traumatic rupture of the thoracic aorta is usually
      caused by blunt vascular injuries due to deceleration. The aortic injury is
      generally located distal to the left subclavian artery. Even without further
      thoracic lesions, a computer tomography should be performed in the emergency
      room, because a rupture can exist even in the absence of symptoms. The
      traditional therapeutic option is open, left thoracotomy followed by direct
      aortic reconstruction. Alternatively, endovascular implantation of a thoracic
      stent graft can be performed immediately in urgent situations or, with delayed
      priority, under systematically management of the blood pressure. In this article,
      not only the mechanisms of injury but also diagnostic and therapeutic options of
      traumatic rupture of the thoracic aorta are described. As depicted by two case
      histories, potential symptoms and prognosis of patients with this life
      threatening vascular lesion depend on accompanying injuries. With rapid diagnosis
      and treatment, there is the possibility of good recovery from traumatic aortic
      rupture.

PMID- 22139060
TI  - [Network "cirsmedical.de" and what is the benefit for trauma surgeons?].

PMID- 22139062
TI  - Convergent, modular expression of ebony and tan in the mimetic wing patterns of
      Heliconius butterflies.
AB  - The evolution of pigmentation in vertebrates and flies has involved repeated
      divergence at a small number of genes related to melanin synthesis. Here, we
      study insect melanin synthesis genes in Heliconius butterflies, a group
      characterised by its diversity of wing patterns consisting of black (melanin),
      and yellow and red (ommochrome) pigmented scales. Consistent with their
      respective biochemical roles in Drosophila melanogaster, ebony is upregulated in
      non-melanic wing regions destined to be pigmented red whilst tan is upregulated
      in melanic regions. Wing regions destined to be pigmented yellow, however, are
      downregulated for both genes. This pattern is conserved across multiple divergent
      and convergent phenotypes within the Heliconii, suggesting a conserved mechanism
      for the development of black, red and yellow pattern elements across the genus.
      Linkage mapping of five melanin biosynthesis genes showed that, in contrast to
      other organisms, these genes do not control pattern polymorphism. Thus, the
      pigmentation genes themselves are not the locus of evolutionary change but lie
      downstream of a wing pattern regulatory factor. The results suggest a modular
      system in which particular combinations of genes are switched on whenever red,
      yellow or black pattern elements are favoured by natural selection for diverse
      and mimetic wing patterns.

PMID- 22139063
TI  - Estrus cycle effect on muscle tyrosine kinase activity in bitches.
AB  - Estrus cycle is a well recognized cause of insulin resistance in bitches. The
      insulin receptor (IR) as well as the insulin-like growth factor-I receptor belong
      to the same subfamily of tyrosine kinase (TK) receptors. The objective of this
      study was to evaluate basal TK activity in muscle tissue of bitches during the
      estrus cycle. Twenty-four bitches were used in the study (7 in anestrus, 7 in
      estrus, and 10 in diestrus). Muscle samples, taken after spaying surgery to
      determine TK activity, were immediately frozen in liquid nitrogen and then stored
      at -80 degrees C until the membranes were prepared by sequential centrifugation
      after being homogenized. TK activity was determined by Poly (Glu 4:Tyr 1)
      phosphorylation and expressed in cpm/MUg of protein. TK activity was
      significantly lower (P < 0.001) in the animals in estrus (104.5 +/- 11.9 cpm/MUg
      of protein) and diestrus (94.5 +/- 16.9 cpm/MUg of protein) when compared with
      bitches in anestrus (183.2 +/- 39.2 cpm/MUg of protein). These results
      demonstrate, for the first time, lower basal TK activity in the muscle tissue of
      female dogs during estrus and diestrus, which may represent lower insulin
      signaling capacity, opening a new field of investigation into the molecular
      mechanisms of insulin resistance in dogs.

PMID- 22139064
TI  - The use of controlled surface topography and flow-induced shear stress to
      influence renal epithelial cell function.
AB  - Physiologically-representative and well-controlled in vitro models of human
      tissue provide a means to safely, accurately, and rapidly develop therapies for
      disease. Current in vitro models do not possess appropriate levels of cell
      function, resulting in an inaccurate representation of in vivo physiology.
      Mechanical parameters, such as sub-micron topography and flow-induced shear
      stress (FSS), influence cell functions such as alignment, migration,
      differentiation and phenotypic expression. Combining, and independently
      controlling, biomaterial surface topography and FSS in a cell culture device
      would provide a means to control cell function resulting in more physiologically
      representative in vitro models of human tissue. Here we develop the Microscale
      Tissue Modeling Device (MTMD) which couples a topographically-patterned substrate
      with a microfluidic chamber to control both topographic and FSS cues to cells.
      Cells from the human renal proximal tubule cell line HK-2 were cultured in the
      MTMD and exposed to topographic patterns and several levels of FSS
      simultaneously. Results show that the biomaterial property of surface topography
      and FSS work in concert to elicit cell alignment and influence tight junction
      (TJ) formation, with topography enhancing cell response to FSS. By administering
      independently-controlled mechanical parameters to cell populations, the MTMD
      creates a more realistic in vitro model of human renal tissue.

PMID- 22139065
TI  - First clinical pharmacokinetic dose-escalation study of sagopilone, a novel,
      fully synthetic epothilone, in Japanese patients with refractory solid tumors.
AB  - PURPOSE: Sagopilone has recently been identified and preferentially used for the
      treatment of taxane-resistant cancer. The purpose of this dose-escalation study
      was to investigate the safety, tolerability, and pharmacokinetics (PK) of
      sagopilone in refractory solid tumors. METHODS: A total of 17 Japanese patients
      received sagopilone in this Phase I study. Sagopilone was given as a 30-min
      intravenous infusion once every 3 weeks (one course) with an initial dose of 12.4
      mg/m(2) up to 22.0 mg/m(2) for a maximum of 6 courses. RESULTS: The maximum
      tolerated dose (MTD) was determined to be 16.5 mg/m(2). The major dose-limiting
      toxicity (DLT) was peripheral sensory neuropathy. The PK data demonstrated that
      sagopilone did not accumulate after repeated administration. Two patients had
      stable disease (SD) over a period of 12 weeks. CONCLUSIONS: Our study
      demonstrated clinically favorable safety, tolerability, and efficacy of
      sagopilone, which will help define the treatment of advanced tumors in more
      extensive clinical trials.

PMID- 22139066
TI  - Importance of day 21 BM chimerism in sustained neutrophil engraftment following
      double-unit cord blood transplantation.
AB  - Delayed or failed engraftment remains a concern after cord blood transplantation
      (CBT) even when using double-unit grafts. Therefore, we analyzed the association
      between BM assessment performed approximately 21 days after transplantation, and
      the speed and success of sustained donor-derived neutrophil engraftment in 56
      myeloablative double-unit CBT (DCBT) recipients. Overall, the cumulative
      incidence of sustained neutrophil engraftment was 95% (95% confidence intervals
      (CI): 89-100). Of the percentage of myeloid precursors, the BM cellularity and
      the total donor chimerism the total donor chimerism percentage had the most
      critical association with the speed and success of engraftment. DCBT recipients
      who were 100% donor achieved a 98% engraftment rate at a median of 22 days. This
      compared with 100% engraftment in patients who were 90-99% donor, but at a
      delayed median of 29 days and only 68% engraftment in patients <90% donor at a
      median of 37 days (P=0.001). Multivariate analysis was performed in the subgroup
      of patients who had not engrafted at the time the BM analysis was performed, the
      subgroup of most clinical concern. This confirmed donor chimerism was predictive
      of subsequent neutrophil recovery (P=0.004). These findings demonstrate the
      importance of the day 21 BM chimerism determinations after DCBT.

PMID- 22139067
TI  - Optimizing a photoallodepletion protocol for adoptive immunotherapy after
      haploidentical SCT.
AB  - In adults, one-haplotype-mismatched haematopoietic SCT (haploidentical HSCT) is
      associated with slow immune recovery due to decaying thymic function and
      extensive T-cell depletion of the graft. Although essential for preventing GVHD,
      T-cell depletion underlies the major reasons for transplant failure: leukemia
      relapse and infections, with infection-related mortality accounting for about 40%
      of non-leukemic deaths. Adoptive T-cell therapy would be helpful for these
      patients but to administer it without causing GVHD, alloreactive T cells need to
      be eliminated from donor T lymphocytes before infusion. In a preclinical study,
      to address this problem, we determined the efficacy of photodynamic purging of
      alloreactive T cells, by investigating combinations of parameters in order to
      achieve maximum allodepletion, preservation of T-regulatory cells and of pathogen
      and leukemia-specific T-cell responses in donor-vs-recipient MLR. We also needed
      to identify an optimal method to quantify the Ag-specific T-cell repertoires.
      Optimal procedures were identified. In particular, we compared limiting-dilution
      analyses (LDA) of proliferating T cells with H(3)-thymidine incorporation by bulk
      T cells and with flow cytometry CD25 expression, which is accepted as a T-cell
      activation marker. This study demonstrated that LDA is a reliable, predictable
      and sensitive method for measuring alloreactive, pathogen- and leukemia-specific
      T-cell frequencies.

PMID- 22139068
TI  - Is it time to revisit our current hematopoietic progenitor cell quantification
      methods in the clinic?
AB  - In the clinical practice of hematopoietic SCT, the minimum numbers of cells
      required for a successful engraftment are defined on the basis of their CD45 and
      CD34 expression profiles. However, the quantity of earlier progenitors or CD34
      positive cells at different differentiation stages within stem cell grafts is not
      generally taken into consideration. During the last decade, various teams have
      quantified the number of cells expressing various combinations of CD34, CD38,
      CD133, CD90 co-expression and/or aldehyde dehydrogenase functional capacity using
      flow cytometry. Some of these studies resulted in the greater appreciation that
      combinations of these Ags were associated with varied myeloid, erythroid and
      platelet engraftment rates whereas others showed that the relative absence or
      presence of these markers could define cells responsible for either short- or
      long-term engraftment. These findings were also extended to differences between
      progenitor cell populations found within BM vs peripheral or cord-blood grafts.
      Cells harvested from donors are also generally frozen and stored; thawed cells
      have variable levels of viability and functional capacity based on the time
      tested post thaw, which also can be assessed by flow cytometry. Finally, flow
      cytometry has the potential for analysis of cells carrying a mesenchymal stem
      cell phenotype, which may be quiescent within some of the stem cell products.
      This review will address the need for stem cell subpopulation quantification and
      summarize existing published data to identify some Ags and functional
      characteristics that can be applicable to daily clinical practice.

PMID- 22139069
TI  - Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR)
      on high-risk patients with myeloid and lymphoid malignancies undergoing reduced
      intensity transplantation from haploidentical related donors.
AB  - The impact of activating KIR (aKIR) and inhibitory KIR (iKIR) on OS, relapse
      related mortality (RRM) and acute GVHD (aGVHD) was prospectively studied in 84
      adults with high-risk hematologic malignancies receiving reduced intensity
      conditioning (RIC) T-cell depleted hematopoietic SCT (HSCT) from haploidentical
      related donors. In this clinical model, freedom from RRM is dependent on GVL
      effect. Patients were divided into myeloid (n=49) and lymphoid (n=35) malignancy
      groups. KIR-ligand and ligand-ligand models were studied in both GVH and
      rejection directions and statistically correlated with outcome measures. In the
      myeloid group, OS was higher (P=0.009) and RRM was lower (P=0.036) in patients
      missing HLA-C group2 ligand to donor iKIR. OS was higher if patients had >1
      missing ligand (P=0.018). In lymphoid malignancy, missing ligand to donor KIR had
      no impact on OS or RRM. However, OS was better with donor aKIR 2DS2 (P=0.028).
      There was a trend towards shorter OS in recipient with KIR 2DS1, 2DS5 and 3DS1,
      although sample sizes were too small to provide inferential statistics. Findings
      in lymphoid malignancy patients should be further studied. These results suggest
      that the absence of appropriate HLA ligands in the recipient to donor iKIR may
      induce GVL without aGVHD in myeloid malignancy patients undergoing TCD-RIC
      transplants.

PMID- 22139070
TI  - Patient information in stem cell transplantation from the perspective of health
      care professionals: a survey from the Nurses Group of the European Group for
      Blood and Marrow Transplantation.

PMID- 22139071
TI  - Targeting the epigenome for treatment of cancer.
AB  - Cancer genome analyses have revealed that the enzymes involved in epigenetic gene
      regulation are frequently deregulated in cancer. Here we describe the enzymes
      that control the epigenetic state of the cell, how they are affected in cancer
      and how this knowledge can be exploited to treat cancer with a new arsenal of
      selective therapies.

PMID- 22139072
TI  - The cocaine- and amphetamine-regulated transcript mediates ligand-independent
      activation of ERalpha, and is an independent prognostic factor in node-negative
      breast cancer.
AB  - Personalized medicine requires the identification of unambiguous prognostic and
      predictive biomarkers to inform therapeutic decisions. Within this context, the
      management of lymph node-negative breast cancer is the subject of much debate
      with particular emphasis on the requirement for adjuvant chemotherapy. The
      identification of prognostic and predictive biomarkers in this group of patients
      is crucial. Here, we demonstrate by tissue microarray and automated image
      analysis that the cocaine- and amphetamine-regulated transcript (CART) is
      expressed in primary and metastatic breast cancer and is an independent poor
      prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors
      in two separate breast cancer cohorts (n=690; P=0.002, 0.013). We also show that
      CART increases the transcriptional activity of ERalpha in a ligand-independent
      manner via the mitogen-activated protein kinase pathway and that CART stimulates
      an autocrine/paracrine loop within tumor cells to amplify the CART signal.
      Additionally, we demonstrate that CART expression in ER-positive breast cancer
      cell lines protects against tamoxifen-mediated cell death and that high CART
      expression predicts disease outcome in tamoxifen-treated patients in vivo in
      three independent breast cancer cohorts. We believe that CART profiling will help
      facilitate stratification of lymph node-negative breast cancer patients into high
      and low-risk categories and allow for the personalization of therapy.

PMID- 22139073
TI  - Downregulation of HMGA-targeting microRNAs has a critical role in human pituitary
      tumorigenesis.
AB  - Previous studies have demonstrated that high mobility group A proteins have a
      critical role on the onset of human pituitary adenomas. Indeed, both high
      mobility group A (HMGA) genes are overexpressed in pituitary adenomas, and
      consistently transgenic mice overexpressing either the Hmga1 or the Hmga2 gene
      develop mixed growth hormone/prolactin (GH-PRL)-secreting pituitary adenomas.
      Trisomy of chromosome 12, where HMGA2 is located, and/or amplification of the
      HMGA2 gene locus account for the HMGA2 overexpression in most human
      prolactinomas. Conversely, HMGA1 overexpression is not associated to any
      rearrangement or amplification of the HMGA1 locus. We have first identified micro
      RNAs (miRNAs) able to target both HMGA1 and HMGA2 messenger RNAs. Then, all of
      these miRNAs have been found downregulated in pituitary adenomas of different
      histotypes, compared with normal pituitary. Interestingly, their downregulation
      was also observed in nonfunctioning pituitary adenomas where HMGA2 overexpression
      is not associated to any alteration of the HMGA2 locus. Functional studies show
      that all these HMGA-targeting miRNAs inhibit the proliferation of the rat
      pituitary adenoma cell line GH3. Therefore, these results indicate that the
      downregulation of the miRNAs able to target the HMGA genes could contribute to
      increase HMGA protein levels in human pituitary adenomas, and then to pituitary
      tumorigenesis.

PMID- 22139075
TI  - Defining MAP3 kinases required for MDA-MB-231 cell tumor growth and metastasis.
AB  - Analysis of patient tumors suggests that multiple MAP3 kinases (MAP3Ks) are
      critical for growth and metastasis of cancer cells. MAP3Ks selectively control
      the activation of extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N
      terminal kinase (JNK), p38 and ERK5 in response to receptor tyrosine kinases and
      GTPases. We used MDA-MB-231 cells because of their ability to metastasize from
      the breast fat pad to distant lymph nodes for an orthotopic xenograft model to
      screen the function of seven MAP3Ks in controlling tumor growth and metastasis.
      Stable short hairpin RNA (shRNA) knockdown was used to inhibit the expression of
      each of the seven MAP3Ks, which were selected for their differential regulation
      of the MAPK network. The screen identified two MAP3Ks, MEKK2 and MLK3, whose
      shRNA knockdown caused significant inhibition of both tumor growth and
      metastasis. Neither MEKK2 nor MLK3 have been previously shown to regulate tumor
      growth and metastasis in vivo. These results demonstrated that MAP3Ks, which
      differentially activate JNK, p38 and ERK5, are necessary for xenograft tumor
      growth and metastasis of MDA-MB-231 tumors. The requirement for MAP3Ks signaling
      through multiple MAPK pathways explains why several members of the MAPK network
      are activated in cancer. MEKK2 was required for epidermal growth factor receptor
      and Her2/Neu activation of ERK5, with ERK5 being required for metastasis. Loss of
      MLK3 expression increased mitotic infidelity and apoptosis in vitro. Knockdown of
      MEKK2 and MLK3 resulted in increased apoptosis in orthotopic xenografts relative
      to control tumors in mice, inhibiting both tumor growth and metastasis; MEKK2 and
      MLK3 represent untargeted kinases in tumor biology for potential therapeutic
      development.

PMID- 22139074
TI  - Foxm1 transcription factor is required for macrophage migration during lung
      inflammation and tumor formation.
AB  - Macrophages have a key role in tumor-associated pulmonary inflammation that
      supports the proliferation of tumor cells and promotes lung tumor growth.
      Although increased numbers of tumor-associated macrophages are linked to poor
      prognosis in lung cancer patients, little is known regarding the transcriptional
      mechanisms controlling recruitment of macrophages during lung tumorigenesis.
      Forkhead Box m1 (Foxm1) transcription factor is induced in multiple cell types
      within tumor lesions and its increased expression is associated with poor
      prognosis in patients with lung adenocarcinomas. To determine the role of Foxm1
      in recruitment of tumor-associated macrophages, a mouse line with macrophage
      specific Foxm1 deletion was generated (macFoxm1(-/-)). Lung tumorigenesis was
      induced using a 3-methylcholanthrene/butylated hydroxytoluene (BHT; 3,5-di-t
      butyl-4-hydroxytoluene) tumor initiation/promotion protocol. Ablation of Foxm1 in
      macrophages reduced the number and size of lung tumors in macFoxm1(-/-) mice.
      Decreased tumorigenesis was associated with diminished proliferation of tumor
      cells and decreased recruitment of macrophages during the early stages of tumor
      formation. The expression levels of the pro-inflammatory genes iNOS, Cox-2,
      interleukin-1b (IL-1b) and IL-6, as well as the migration-related genes
      macrophage inflammatory protein-1 (MIP-1alpha), MIP-2 and MMP-12, were decreased
      in macrophages isolated from macFoxm1(-/-) mice. Migration of Foxm1-deficient
      macrophages was reduced in vitro. The chemokine receptors responsible for
      monocyte recruitment to the lung, CX(3)CR1 and CXCR4, were decreased in Foxm1
      deficient monocytes. In co-transfection experiments, Foxm1 directly bound to and
      transcriptionally activated the CX(3)CR1 promoter. Adoptive transfer of wild-type
      monocytes to macFoxm1(-/-) mice restored BHT-induced pulmonary inflammation to
      the levels observed in control mice. Expression of Foxm1 in macrophages is
      required for pulmonary inflammation, recruitment of macrophages into tumor sites
      and lung tumor growth.

PMID- 22139076
TI  - MiR-135a functions as a selective killer of malignant glioma.
AB  - Glioma is the most common and fatal primary brain tumor. Thus far, therapeutic
      strategies to efficiently and specifically antagonize glioma are limited and
      poorly developed. Here we report that glia-enriched miR-135a, a microRNA that is
      dramatically downregulated in malignant glioma and correlated with the
      pathological grading, is capable of inducing mitochondria-dependent apoptosis of
      malignant glioma by regulating various genes including STAT6, SMAD5 and BMPR2, as
      well as affecting the signaling pathway downstream. Moreover, this lethal effect
      is selectively towards malignant glioma cells, but not neurons and glial cells,
      through a novel mechanism. Our findings suggest an important role of miR-135a in
      glioma etiology and provide a potential candidate for malignant glioma therapy.

PMID- 22139078
TI  - Inflammation-induced repression of tumor suppressor miR-7 in gastric tumor cells.
AB  - Inflammation has an important role in cancer development through various
      mechanisms. It has been shown that dysregulation of microRNAs (miRNAs) that
      function as oncogenes or tumor suppressors contributes to tumorigenesis. However,
      the relationship between inflammation and cancer-related miRNA expression in
      tumorigenesis has not yet been fully understood. Using K19-C2mE and Gan mouse
      models that develop gastritis and gastritis-associated tumors, respectively, we
      found that 21 miRNAs were upregulated, and that 29 miRNAs were downregulated in
      gastric tumors in an inflammation-dependent manner. Among these miRNAs, the
      expression of miR-7, a possible tumor suppressor, significantly decreased in both
      gastritis and gastric tumors. Moreover, the expression of miR-7 in human gastric
      cancer was inversely correlated with the levels of interleukin-1beta and tumor
      necrosis factor-alpha, suggesting that miR-7 downregulation is related to the
      severity of inflammatory responses. In the normal mouse stomach, miR-7 expression
      was at a basal level in undifferentiated gastric epithelial cells, and was
      induced during differentiation. Moreover, transfection of a miR-7 precursor into
      gastric cancer cells suppressed cell proliferation and soft agar colony
      formation. These results suggest that suppression of miR-7 expression is
      important for maintaining the undifferentiated status of gastric epithelial
      cells, and thus contributes to gastric tumorigenesis. Although epigenetic changes
      were not found in the CpG islands around miR-7-1 of gastritis and gastric tumor
      cells, we found that activated macrophage-derived small molecule(s) (<3 kDa) are
      responsible for miR-7 repression in gastric cancer cells. Furthermore, the miR-7
      expression level significantly decreased in the inflamed gastric mucosa of
      Helicobacter-infected mice, whereas it increased in the stomach of germfree K19
      C2mE and Gan mice wherein inflammatory responses were suppressed. Taken together,
      these results indicate that downregulation of tumor suppressor miR-7 is a novel
      mechanism by which the inflammatory response promotes gastric tumorigenesis.

PMID- 22139077
TI  - EGFRvIII promotes glioma angiogenesis and growth through the NF-kappaB,
      interleukin-8 pathway.
AB  - Sustaining a high growth rate requires tumors to exploit resources in their
      microenvironment. One example of this is the extensive angiogenesis that is a
      typical feature of high-grade gliomas. Here, we show that expression of the
      constitutively active mutant epidermal growth factor receptor, DeltaEGFR
      (EGFRvIII, EGFR*, de2-7EGFR) is associated with significantly higher expression
      levels of the pro-angiogenic factor interleukin (IL)-8 in human glioma specimens
      and glioma stem cells. Furthermore, the ectopic expression of DeltaEGFR in
      different glioma cell lines caused up to 60-fold increases in the secretion of IL
      8. Xenografts of these cells exhibit increased neovascularization, which is not
      elicited by cells overexpressing wild-type (wt)EGFR or DeltaEGFR with an
      additional kinase domain mutation. Analysis of the regulation of IL-8 by site
      directed mutagenesis of its promoter showed that DeltaEGFR regulates its
      expression through the transcription factors nuclear factor (NF)-kappaB,
      activator protein 1 (AP-1) and CCAAT/enhancer binding protein (C/EBP). Glioma
      cells overexpressing DeltaEGFR showed constitutive activation and DNA binding of
      NF-kappaB, overexpression of c-Jun and activation of its upstream kinase c-Jun N
      terminal kinase (JNK) and overexpression of C/EBPbeta. Selective pharmacological
      or genetic targeting of the NF-kappaB or AP-1 pathways efficiently blocked
      promoter activity and secretion of IL-8. Moreover, RNA interference-mediated
      knock-down of either IL-8 or the NF-kappaB subunit p65, in DeltaEGFR-expressing
      cells attenuated their ability to form tumors and to induce angiogenesis when
      injected subcutaneously into nude mice. On the contrary, the overexpression of IL
      8 in glioma cells lacking DeltaEGFR potently enhanced their tumorigenicity and
      produced highly vascularized tumors, suggesting the importance of this cytokine
      and its transcription regulators in promoting glioma angiogenesis and tumor
      growth.

PMID- 22139079
TI  - The transcriptional coactivators megakaryoblastic leukemia 1/2 mediate the
      effects of loss of the tumor suppressor deleted in liver cancer 1.
AB  - Deleted in Liver Cancer 1 (DLC1) is a tumor suppressor whose allele is lost in
      50% of liver, breast, lung and 70% of colon cancers. Here, we show that the
      transcriptional coactivators Megakaryoblastic Leukemia 1 and 2 (MKL1/2) are
      constitutively localized to the nucleus in hepatocellular and mammary carcinoma
      cells that lack DLC1. Moreover, DLC1 loss and MKL1 nuclear localization correlate
      in primary human hepatocellular carcinoma. Nuclear accumulation of MKL1 in DLC1
      deficient cancer cells is accomplished by activation of the RhoA/actin signaling
      pathway and concomitant impairment of MKL1 phosphorylation, which results in
      constitutive activation of MKL1/2 target genes. We provide evidence that MKL1/2
      mediates cancerous transformation in DLC1-deficient hepatocellular and mammary
      carcinoma cells. Depletion of MKL1/2 suppresses cell migration, cell
      proliferation and anchorage-independent cell growth induced by DLC1 loss.

PMID- 22139080
TI  - Suppression of Tumorigenicity-14, encoding matriptase, is a critical suppressor
      of colitis and colitis-associated colon carcinogenesis.
AB  - Colitis-associated colorectal cancers are an etiologically distinct subgroup of
      colon cancers that occur in individuals suffering from inflammatory bowel disease
      and arise as a consequence of persistent exposure of hyperproliferative
      epithelial stem cells to an inflammatory microenvironment. An intrinsic defect in
      the intestinal epithelial barrier has been proposed to be one of several factors
      that contribute to the inappropriate immune response to the commensal microbiota
      that underlies inflammatory bowel disease. Matriptase is a membrane-anchored
      serine protease encoded by Suppression of Tumorigenicity-14 (ST14) that
      strengthens the intestinal epithelial barrier by promoting tight junction
      formation. Here, we show that intestinal epithelial-specific ablation of St14 in
      mice causes formation of colon adenocarcinoma with very early onset and high
      penetrance. Neoplastic progression is preceded by a chronic inflammation of the
      colon that resembles human inflammatory bowel disease and is promoted by the
      commensal microbiota. This study demonstrates that inflammation-associated colon
      carcinogenesis can be initiated and promoted solely by an intrinsic intestinal
      permeability barrier perturbation, establishes St14 as a critical tumor
      suppressor gene in the mouse gastrointestinal tract and adds matriptase to the
      expanding list of pericellular proteases with tumor-suppressive functions.

PMID- 22139081
TI  - Modeling invasive breast cancer: growth factors propel progression of HER2
      positive premalignant lesions.
AB  - The HER2/neu oncogene encodes a receptor-like tyrosine kinase whose
      overexpression in breast cancer predicts poor prognosis and resistance to
      conventional therapies. However, the mechanisms underlying aggressiveness of HER2
      (human epidermal growth factor receptor 2)-overexpressing tumors remain
      incompletely understood. Because it assists epidermal growth factor (EGF) and
      neuregulin receptors, we overexpressed HER2 in MCF10A mammary cells and applied
      growth factors. HER2-overexpressing cells grown in extracellular matrix formed
      filled spheroids, which protruded outgrowths upon growth factor stimulation. Our
      transcriptome analyses imply a two-hit model for invasive growth: HER2-induced
      proliferation and evasion from anoikis generate filled structures, which are
      morphologically and transcriptionally analogous to preinvasive patients' lesions.
      In the second hit, EGF escalates signaling and transcriptional responses leading
      to invasive growth. Consistent with clinical relevance, a gene expression
      signature based on the HER2/EGF-activated transcriptional program can predict
      poorer prognosis of a subgroup of HER2-overexpressing patients. In conclusion,
      the integration of a three-dimensional cellular model and clinical data
      attributes progression of HER2-overexpressing lesions to EGF-like growth factors
      acting in the context of the tumor's microenvironment.

PMID- 22139082
TI  - Identification of novel CHD1-associated collaborative alterations of genomic
      structure and functional assessment of CHD1 in prostate cancer.
AB  - A clearer definition of the molecular determinants that drive the development and
      progression of prostate cancer (PCa) is urgently needed. Efforts to map recurrent
      somatic deletions in the tumor genome, especially homozygous deletions (HODs),
      have provided important positional information in the search for cancer-causing
      genes. Analyzing HODs in the tumors of 244 patients from two independent cohorts
      and 22 PCa xenografts using high-resolution single-nucleotide polymorphism
      arrays, herein we report the identification of CHD1, a chromatin remodeler, as
      one of the most frequently homozygously deleted genes in PCa, second only to PTEN
      in this regard. The HODs observed in CHD1, including deletions affecting only
      internal exons of CHD1, were found to completely extinguish the expression of
      mRNA of this gene in PCa xenografts. Loss of this chromatin remodeler in clinical
      specimens is significantly associated with an increased number of additional
      chromosomal deletions, both hemi- and homozygous, especially on 2q, 5q and 6q.
      Together with the deletions observed in HEK293 cells stably transfected with CHD1
      small hairpin RNA, these data suggest a causal relationship. Downregulation of
      Chd1 in mouse prostate epithelial cells caused dramatic morphological changes
      indicative of increased invasiveness, but did not result in transformation.
      Indicating a new role of CHD1, these findings collectively suggest that distinct
      CHD1-associated alterations of genomic structure evolve during and are required
      for the development of PCa.

PMID- 22139083
TI  - A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance
      and a potential target for therapy in ovarian cancer.
AB  - Germline variants in the 3' untranslated region (3'UTR) of cancer genes
      disrupting microRNA (miRNA) regulation have recently been associated with cancer
      risk. A variant in the 3'UTR of the KRAS oncogene, referred to as the KRAS
      variant, is associated with both cancer risk and altered tumor biology. Here, we
      test the hypothesis that the KRAS variant can act as a biomarker of outcome in
      epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in
      KRAS variant-positive EOC patients. As this variant seems to be associated with
      tumor biology, we additionally test the hypothesis that this variant can be
      directly targeted to impact cell survival. EOC patients with complete clinical
      data were genotyped for the KRAS variant and analyzed for outcome (n=536),
      response to neoadjuvant chemotherapy (n=125) and platinum resistance (n=306).
      Outcome was separately analyzed for women with known BRCA mutations (n=79). Gene
      expression was analyzed on a subset of tumors with available tissue. Cell lines
      were used to confirm altered sensitivity to chemotherapy associated with the KRAS
      variant. Finally, the KRAS variant was directly targeted through small
      interfering RNA/miRNA oligonucleotides in cell lines and survival was measured.
      Postmenopausal EOC patients with the KRAS variant were significantly more likely
      to die of ovarian cancer by multivariate analysis (hazard ratio=1.67, 95%
      confidence interval: 1.09-2.57, P=0.019, n=279). Perhaps explaining this finding,
      EOC patients with the KRAS variant were significantly more likely to be platinum
      resistant (odds ratio=3.18, confidence interval: 1.31-7.72, P=0.0106, n=291). In
      addition, direct targeting of the KRAS variant led to a significant reduction in
      EOC cell growth and survival in vitro. These findings confirm the importance of
      the KRAS variant in EOC, and indicate that the KRAS variant is a biomarker of
      poor outcome in EOC likely due to platinum resistance. In addition, this study
      supports the hypothesis that these tumors have continued dependence on such 3'UTR
      lesions, and that direct targeting may be a viable future treatment approach.

PMID- 22139085
TI  - Implementation of pharmacotherapy guidelines in heart failure: experience from
      the German Competence Network Heart Failure.
AB  - AIM: To evaluate the implementation of current pharmacotherapy guidelines of
      heart failure and to identify factors associated with high pharmacotherapy
      guideline adherence in heart failure patients. METHODS AND RESULTS: We pooled
      data from seven studies performed in the context of the German Competence Network
      Heart Failure selecting patients with chronic systolic heart failure and left
      ventricular ejection fraction (LVEF) <45% (n = 2,682). The quality of
      pharmacotherapy was evaluated by calculating the guideline adherence indicator
      (GAI), which considers three (GAI-3) or five (GAI-5) of the recommended heart
      failure substance classes and accounts for respective contraindications. GAI-3
      was categorized as perfect (GAI = 100%: 71% of the cohort), medium (GAI = 50-99%:
      22%), and poor adherence (GAI <50%: 7%). In ordinal regression, the following
      factors were positively associated with perfect adherence: history of
      revascularization (odds ratio 1.59, 95% confidence interval 1.27-1.98), prior ICD
      implantation (2.29, 1.76-2.98), and LV ejection fraction <30% (1.45, 1.19-1.76),
      whereas age (per 10 years; 0.82, 0.77-0.89), NYHA III/IV (0.15, 0.12-0.18),
      unknown duration of heart failure (0.69, 0.53-0.89), and antidepressant
      medication (0.61, 0.42-0.88) were negatively associated with perfect adherence.
      Better GAI-3 at baseline predicted favorable changes of LV ejection fraction and
      end-diastolic diameter after 1 year. One-year mortality risk was closely related
      to GAI-3 in both groups of NYHA functional class I/II (excellent vs. poor GAI-3:
      7.2 vs. 14.5%, log rank = 0.004) and class III/IV (13.5 vs. 21.5%, log rank =
      0.005). CONCLUSIONS: This large pooled analysis showed that a high level of
      guideline adherence is achievable in the context of clinical studies. Those
      receiving and tolerating optimal pharmacotherapy experience a better prognosis.
      Nevertheless, the implementation of heart failure medication needs further
      improvement in female and elderly patients, especially those in NYHA functional
      class >II and patients with LVEF >=30%.

PMID- 22139084
TI  - The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell
      stemness through Wnt/beta-catenin signaling and silenced in common carcinomas.
AB  - Genetic alterations of 16q21-q22, the locus of a 6-cadherin cluster, are
      frequently involved in multiple tumors, suggesting the presence of critical tumor
      suppressor genes (TSGs). Using 1 Mb array comparative genomic hybridization
      (aCGH), we refined a small hemizygous deletion (~1 Mb) at 16q21-22.1, which
      contains a single gene Cadherin-11 (CDH11, OB-cadherin). CDH11 was broadly
      expressed in human normal adult and fetal tissues, while its silencing and
      promoter CpG methylation were frequently detected in tumor cell lines, but not in
      immortalized normal epithelial cells. Aberrant methylation was also frequently
      detected in multiple primary tumors. CDH11 silencing could be reversed by
      pharmacologic or genetic demethylation, indicating an epigenetic mechanism.
      Ectopic expression of CDH11 strongly suppressed tumorigenecity and induced tumor
      cell apoptosis. Moreover, CDH11 was found to inhibit Wnt/beta-catenin and AKT/Rho
      A signaling, as well as actin stress fiber formation, thus further inhibiting
      tumor cell migration and invasion. CDH11 also inhibited epithelial-to-mesenchymal
      transition and downregulated stem cell markers. Thus, our work identifies CDH11
      as a functional tumor suppressor and an important antagonist of Wnt/beta-catenin
      and AKT/Rho A signaling, with frequent epigenetic inactivation in common
      carcinomas.

PMID- 22139086
TI  - Whole-body diffusion-weighted MRI in a case of Rosai-Dorfman disease with
      exclusive multifocal skeletal involvement.
AB  - Rosai-Dorfman disease (RDD) is a rare disorder and usually presents with painless
      bilateral cervical lymphadenopathy. About 43% of RDD patients show extranodal
      involvement, including bones (8%). As RDD is a systemic disease, which can
      involve lymph nodes, bones, skin, kidneys, respiratory tract, parotid gland,
      orbital cavity and the central nervous system, whole-body imaging may be useful
      for the assessment of extent, distribution and follow-up of disease. Whole-body
      diffusion-weighted MRI is able to demonstrate lesions and to assess therapy
      response without the need for radiation or intravenous contrast agent. Here, we
      report a case of a 15-year-old boy with primary skeletal RDD without
      lymphadenopathy, who was staged and followed by whole-body diffusion-weighted
      MRI.

PMID- 22139087
TI  - The prognostic nutritional index can be a prognostic indicator in colorectal
      carcinoma.
AB  - PURPOSE: Preoperative assessments regarding a patient's immunological and
      nutritional condition are required to predict the outcomes of patients with
      malignant tumors. The aim of the current study was to clarify the significance of
      Onodera's prognostic nutritional index (OPNI), which can simply account for the
      immunological and nutritional conditions, in patients with colorectal carcinoma.
      METHODS: The correlations of the preoperative OPNI value with clinicopathological
      features were examined in 219 patients with colorectal carcinoma who had been
      surgically treated. RESULTS: Not only the tumor stage (P = 0.028) and venous
      invasion (P = 0.002), but also an OPNI of less than 40 (P = 0.002) were found to
      be independently correlated with a worse prognosis of patients with colorectal
      carcinoma. CONCLUSION: The preoperative OPNI can be used as a simple prognostic
      indicator in colorectal carcinoma.

PMID- 22139088
TI  - Surgical site infections after post-bariatric abdominoplasty and flank
      liposuction: a case-control study focusing on the quantity of tissue removed.
AB  - We evaluated whether the quantity of fat removed during abdominoplasty and
      liposuction correlated with the occurrence of surgical site infection (SSI). We
      selected patients of similar age, sex, smoking status, obesity, and post
      bariatric weight loss, retrospectively, and classified them into groups according
      to the development of SSI. The total amount of fat removed and aspirated was
      compared. The size of the flap removed from the abdomen and the amount of fat
      aspirated with liposuction differed significantly between the SSI and no-SSI
      groups (1.6 +/- 0.2 vs. 0.6 +/- 0.3 kg and 2 +/- 0.2 vs. 0.9 +/- 0.3 l,
      respectively; p < 0.001). The four SSI patients with the most fat removed (1.4 +/
      0.2 kg) or aspirated (2 +/- 0.1 l kg) had the deepest infections. SSI was
      strongly correlated with the size of flap resection (rho = 0.80; p < 0.001) and
      liposuction (rho = 0.72; p < 0.001). The quantity of fat removed or aspirated can
      influence the occurrence of SSI. If confirmed, these data could be used to better
      stratify patients according to their risk.

PMID- 22139089
TI  - Morphogenesis of Pseudopallene sp. (Pycnogonida, Callipallenidae) I: embryonic
      development.
AB  - Embryonic development of Pycnogonida (sea spiders) is poorly understood in
      comparison to other euarthropod lineages with well-established model organisms.
      However, given that pycnogonids potentially represent the sister group to
      chelicerates or even to all other euarthropods, their development might yield
      important data for the reconstruction of arthropod evolution. Using scanning
      electron microscopy, fluorescent nucleic staining and immunohistochemistry, the
      general course of embryonic morphogenesis in Pseudopallene sp. (Callipallenidae),
      a pycnogonid with prolonged embryonic development, is described. A staging system
      comprising ten stages is presented, which can be used in future studies
      addressing specific developmental processes. The initially slit-like stomodeum
      anlage forms at the anterior end of an eight-shaped germ band and predates
      proboscis outgrowth. The latter process is characterized by the protrusion of
      three cell populations that are subsequently involved in pharynx formation. In
      later stages, the proboscis assumes distally a horseshoe-like shape. At no time,
      a structure corresponding to the euarthropod labrum is detectable. Based on the
      complete lack of palpal and ovigeral embryonic limbs and the early
      differentiation of walking leg segments 1 and 2, the existence of an embryonized
      protonymphon stage during callipallenid development is rejected. The evolution of
      pycnogonid hatching stages, especially within Callipallenidae and Nymphonidae, is
      re-evaluated in the light of recent phylogenetic analyses. Specifically, the re
      emergence of the ancestral protonymphon larva (including re-development of palpal
      and ovigeral larval limbs) and a possible re-appearance of adult palps in the
      nymphonid lineage are discussed. This challenges the perception of pycnogonid
      head appendage evolution as being driven by reduction events alone.

PMID- 22139090
TI  - Tripchlorolide induces cell death in lung cancer cells by autophagy.
AB  - It has been demonstrated that triptolide inhibits the growth of several types of
      cancer cells in vitro and prevents tumor growth in vivo by inducing apoptosis and
      autophagy. Here we showed that Tripchlorolide (T4) significantly suppressed the
      proliferation of A549 cells in a dose- and time-dependent manner. This
      suppressive effect was diminished when cells were pretreated with 3
      Methylamphetamine (3-MA). After the cells were treated with T4, the LC3 II
      protein expression was significantly increased, and autophagosomes were observed
      by TEM. However, almost no apoptosis was observed in A549 treated with T4. These
      results suggest that T4 induces A549 cell death predominantly through the
      activation of the autophagy pathway instead of the apoptosis pathway.

PMID- 22139092
TI  - Ab initio and empirical energy landscapes of (MgF2)n clusters (n = 3, 4).
AB  - We explore the energy landscape of (MgF(2))(3) on both the empirical and ab
      initio level using the threshold algorithm. In order to determine the energy
      landscape and the dynamics of the trimer we investigate not only the stable
      isomers but also the barriers separating these isomers. Furthermore, we study the
      probability flows in order to estimate the stability of all the isomers found. We
      find that there is reasonable qualitative agreement between the ab initio and
      empirical potential, and important features such as sub-basins and energetic
      barriers follow similar trends. However, we observe that the energies are
      systematically different for the less compact clusters, when comparing empirical
      and ab initio energies. Since the underlying motivation of this work is to
      identify the possible clusters present in the gas phase during a low-temperature
      atom beam deposition synthesis of MgF(2), we employ the same procedure to
      additionally investigate the energy landscape of the tetramer. For this case,
      however, we use only the empirical potential.

PMID- 22139093
TI  - Threshold temperatures mediate the impact of reduced snow cover on overwintering
      freeze-tolerant caterpillars.
AB  - Decreases in snow cover due to climate change could alter the energetics and
      physiology of ectothermic animals that overwinter beneath snow, yet how snow
      cover interacts with physiological thresholds is unknown. We applied numerical
      simulation of overwintering metabolic rates coupled with field validation to
      determine the importance of snow cover and freezing to the overwintering lipid
      consumption of the freeze-tolerant Arctiid caterpillar Pyrrharctia isabella.
      Caterpillars that overwintered above the snow experienced mean temperatures 1.3
      degrees C lower than those below snow and consumed 18.36 mg less lipid of a total
      68.97-mg reserve. Simulations showed that linear temperature effects on metabolic
      rate accounted for only 30% of the difference in lipid consumption. When
      metabolic suppression by freezing was included, 93% of the difference between
      animals that overwintered above and below snow was explained. Our results were
      robust to differences in temperature sensitivity of metabolic rate, changes in
      freezing point, and the magnitude of metabolic suppression by freezing. The
      majority of the energy savings was caused by the non-continuous reduction in
      metabolic rate due to freezing, the first example of the importance of
      temperature thresholds in the lipid use of overwintering insects.

PMID- 22139091
TI  - P2Y12 receptor expression is a critical determinant of functional responsiveness
      to ATX's MORFO domain.
AB  - In the central nervous system, the formation of the myelin sheath and the
      differentiation of the myelinating cells, namely oligodendrocytes, are regulated
      by complex signaling networks that involve purinergic receptors and the
      extracellular matrix. However, the exact nature of the molecular interactions
      underlying these networks still needs to be defined. In this respect, the data
      presented here reveal a signaling mechanism that is characterized by an
      interaction between the purinergic P2Y(12) receptor and the matricellular
      extracellular matrix protein autotaxin (ATX), also known as ENPP2,
      phosphodiesterase-Ialpha/ATX, or lysoPLD. ATX has been previously described by us
      to mediate intermediate states of oligodendrocyte adhesion and to enable changes
      in oligodendrocyte morphology that are thought to be crucial for the formation of
      a fully functional myelin sheath. This functional property of ATX is mediated by
      ATX's modulator of oligodendrocyte remodeling and focal adhesion organization
      (MORFO) domain. Here, we show that the expression of the P2Y(12) receptor is
      necessary for ATX's MORFO domain to exert its effects on differentiating
      oligodendrocytes. In addition, our data demonstrate that exogenous expression of
      the P2Y(12) receptor can render cells responsive to the known effects of ATX's
      MORFO domain, and they identify Rac1 as an intracellular factor mediating the
      effect of ATX-MORFO-P2Y(12) signaling on the assembly of focal adhesions. Our
      data further support the idea that a physical interaction between ATX and the
      P2Y(12) receptor provides the basis for an ATX-MORFO-P2Y(12) signaling axis that
      is crucial for mediating cellular states of intermediate adhesion and
      morphological/structural plasticity.

PMID- 22139094
TI  - Rubber friction: comparison of theory with experiment.
AB  - We have measured the friction force acting on a rubber block slid on a concrete
      surface. We used both unfilled and filled (with carbon black) styrene butadiene
      (SB) rubber and have varied the temperature from -10  degrees C to 100  degrees C
      and the sliding velocity from 1 MUm/s to 1000 MUm/s. We find that the
      experimental data at different temperatures can be shifted into a smooth master
      curve, using the temperature-frequency shifting factors obtained from
      measurements of the bulk viscoelastic modulus. The experimental data has been
      analyzed using a theory which takes into account the contributions to the
      friction from both the substrate asperity-induced viscoelastic deformations of
      the rubber, and from shearing the area of real contact. For filled SB rubber the
      frictional shear stress sigma(f) in the area of real contact results mainly from
      the energy dissipation at the opening crack on the exit side of the rubber
      asperity contact regions. For unfilled rubber we instead attribute sigma(f) to
      shearing of a thin rubber smear film, which is deposited on the concrete surface
      during run in. We observe very different rubber wear processes for filled and
      unfilled SB rubber, which is consistent with the different frictional processes.
      Thus, the wear of filled SB rubber results in micrometer-sized rubber particles
      which accumulate as dry dust, which is easily removed by blowing air on the
      concrete surface. This wear process seams to occur at a steady rate. For unfilled
      rubber a smear film forms on the concrete surface, which cannot be removed even
      using a high-pressure air stream. In this case the wear rate appears to slow down
      after some run in time period.

PMID- 22139095
TI  - Confidence-based  medicine.

PMID- 22139096
TI  - [Prehospital maternity care].

PMID- 22139097
TI  - [The fight against HIV--two scenarios].

PMID- 22139098
TI  - [Nobel Prize in medicine 2011].

PMID- 22139099
TI  - [Which tests are best for detection of Chlamydia trachomatis].

PMID- 22139101
TI  - [Cryptogenic cerebral arterial vasospasm].

PMID- 22139103
TI  - [Ethics and reproductive health].

PMID- 22139104
TI  - [Epilepsy and driving licenses].

PMID- 22139105
TI  - [No treatment].

PMID- 22139106
TI  - [More open dialog on global health].

PMID- 22139108
TI  - [Too many journals - for sustained quality research].

PMID- 22139107
TI  - [Too many journals?].

PMID- 22139109
TI  - [All research results should be published].

PMID- 22139110
TI  - [New European guidelines for acute myocardial infarction].

PMID- 22139111
TI  - [Towards more appropriate drug use?].

PMID- 22139113
TI  - The Fukushima accident--health consequences.

PMID- 22139115
TI  - [More evidence and less politics, please!].

PMID- 22139116
TI  - Prehospital  maternity care in Norway.
AB  - BACKGROUND: Out-of-hospital maternity care in Norway is randomly organised and
      not properly formalized. We wished to examine the extent, organisation and
      quality of this service. MATERIAL AND METHOD: We obtained information from the
      Norwegian Medical Birth Registry on all unplanned out-of-hospital births in 2008.
      A questionnaire was sent to all maternity institutions, municipalities and
      emergency dispatch centres, with questions regarding the practical and formal
      organisation of the service using figures from 2008. RESULT: 430 children, all
      above 22 weeks gestation, were born unplanned outside of hospitals in Norway in
      2008. Of these, 194 were born unplanned at home, 189 while being transported and
      47 in other locations (doctor's offices, infirmaries, unknown). Five out of 53
      maternity institutions (9 %) confirmed they had a formal midwife service
      agreement for out-of-hospital births. 247 municipalities (79 %) claimed to have
      no such assistance. Of these, 33 are located at least 90 minutes away from the
      nearest maternity ward. Half of the emergency dispatch centres had no
      registration identifying formal agreements on assistance by midwives for out-of
      hospital births. INTERPRETATION: There is an urgent need to put in place formal
      agreements between the regional health authorities and the municipalities on out
      of-hospital midwife services. A distance of 90 minutes' journey time to a
      maternity ward to fulfil the right to qualified assistance is not well-founded.

PMID- 22139117
TI  - Use of  manual techniques for perineal support in Norwegian maternity
      departments.
AB  - BACKGROUND: The use of supporting techniques to protect the perineum in the last
      phase of birth is controversial. The objective of this investigation was to gain
      more knowledge on the use of hand techniques for perineal support in Norwegian
      maternity wards. MATERIAL AND METHOD: A questionnaire investigation addressed to
      the leaders of all the country''s maternity wards. RESULTS: We received answers
      from 39 of 47 maternity wards (83 %) 34 of the wards said that most of those who
      helped at birth used hand support. 27 wards said that there had been a change in
      practice, and nearly all of them thought that the changes had taken place during
      the last five years. 17 wards had written guidelines on the use of hand support
      techniques. Without exception, use of the hand support technique was recommended.
      Almost half the wards recommended a modified Ritgen's manoeuvre ("the Finnish
      manoeuvre") In many wards the choice of perineal support was left to the
      individual birth helper. INTERPRETATION: Supporting techniques now seem to have
      become standard procedure in the great majority of Norwegian maternity wards. It
      is therefore difficult to carry out a comparative study between the use of hand
      manoeuvres and a passive approach. Further investigation should be carried out on
      whether the introduction of perineal support has had the desired effect.

PMID- 22139118
TI  - Antibiotics prophylaxis in connection with caesarean section--guidelines at
      Norwegian maternity departments.
AB  - BACKGROUND: The frequency of caesarean sections is increasing. Infection in
      operation wounds and/or underlying spaces and organs is a common complication. In
      Veileder I fodselshjelp [Clinical Guidelines in Obstetrics], 2008, antibiotic
      prophylaxis is recommended in the form of single dose ampicillin or first
      generation cephalosporins in connection with acute caesarean sections and under
      special conditions such as prolonged operations. We wanted to find out whether
      Norwegian maternity departments follow these recommendations. MATERIAL AND
      METHODS: All head senior consultants at maternity departments that carried out
      more than one caesarean section in 2008 were invited to take part in a survey of
      the department's written guidelines for use of antibiotic prophylaxis in
      connection with caesarean section. The extent to which the guidelines were
      followed was evaluated using data from the Norwegian Surveillance System for
      Hospital-Associated Infections (NOIS). RESULTS: 38 of the 42 maternity wards in
      the investigation had written guidelines for antibiotic prophylaxis. Four of
      these maternity wards gave prophylaxis in all Caesarean sections, one only on
      indication, and 33 in acute Caesarean section. The guidelines varied as regards
      choice of type of antibiotic and time of administration. In the maternity wards
      with written guidelines recommending use of antibiotic prophylaxis in all
      Caesarean sections, were practice in accordance with the guidelines. When the
      guidelines recommended prophylactic use only in acute operations, there was
      agreement between practice and guidelines in 71 % to 97 % of the patients in the
      ward. INTERPRETATION: Most Norwegian maternity wards have written guidelines on
      antibiotic prophylaxis in Caesarean section. The contents of the guidelines
      varied but are mainly in agreement with current Norwegian recommendations.

PMID- 22139119
TI  - [Advanced MRI methods for assessing functions of the brain].

PMID- 22139120
TI  - [A man with persisting fever, night sweats and high sedimentation rate].
AB  - BACKGROUND: Fever of unknown origin and high sedimentation rate are common
      clinical problems. MATERIAL AND METHODS: A middle-aged man with fever of unknown
      origin, night sweats and high sedimentation rate was referred to our hospital for
      investigation. RESULTS AND INTERPRETATION: The patient was suspected to have
      mononucleosis or reactivation of infectious mononucleosis because of mild anaemia
      and thrombocytopenia, a weakly positive IgM antibody test for Epstein-Barr virus
      and monocytosis (in peripheral blood). Because monocytosis, elevated
      sedimentation rate and fever persisted, bone marrow smears were prepared and
      biopsies taken.The third biopsy showed that morphology was consistent with
      chronic myelomonocytic leukemia (CMML), which was confirmed by two later
      biopsies. However, a malignant cell population (consisting of blasts in
      peripheral blood) was only found in one of several flow cytometry assessments of
      peripheral blood and bone marrow aspirate and cytogenetic analyses of bone marrow
      cells were normal. The patient's clinical situation has been stable for some
      years and treatment has not been necessary.

PMID- 22139121
TI  - [Finding a cancer cell - and determining its origin].

PMID- 22139127
TI  - Rapid assessment of longitudinal systolic left ventricular function using speckle
      tracking of the mitral annulus.
AB  - BACKGROUND: Evaluation of left ventricular function (LV) is one of the most
      important tasks of echocardiography. Left ventricular longitudinal function has
      been recognized to differentiate myocardial disorders better than ejection
      fraction (EF) alone. But recent parameters are still dependent on image quality
      and time consuming. METHODS: Transthoracic echocardiography, tissue Doppler
      imaging, strain imaging and assessment of longitudinal function with a tissue
      motion annular displacement (TMAD) tracking algorithm were performed in 152
      patients with various cardiac pathologies and 47 healthy volunteers in a clinical
      routine setting. RESULTS: Measures of longitudinal function such as LV peak
      systolic strain (SR, r2 = 0.88, p < 0.001) and peak systolic strain rate (SRR, r2
      = 0.78, p < 0.001) correlated highly with TMAD. Tissue motion annular
      displacement was ultrafast and less time-consuming compared to strain imaging
      (8.2 +/- 2.2 s, p < 0.001). Significantly more patients with reduced image
      quality could be analyzed compared to strain imaging (p < 0.001). The intra- and
      inter-observer variabilities were very low with 1.3 +/- 1% and 1.7 +/- 1.2%.
      Tissue motion annular displacement correlated well with clinical parameters
      (NYHA, r = -0.71, p < 0.001) as well as NT-proBNP (r = -0.73, p < 0.001) and
      identified patients with structural heart disease with a significantly higher
      sensitivity 92.1% and specificity 95.7% than did EF, SR, SRR or NT-proBNP (Cut
      off:14.2%,  p < 0.01). In a subgroup of patients with systemic light chain
      amyloidosis and preserved EF (>50%, n = 54), TMAD was significantly reduced,
      especially in those without any signs of cardiac involvement and was superior to
      other parameters of longitudinal function (p < 0.05). CONCLUSIONS: Tissue motion
      annular displacement is a rapid, sensitive and reproducible method for the
      assessment of LV longitudinal function, which is less dependent on image quality.

PMID- 22139128
TI  - Biological mechanism and clinical effect of protein-bound polysaccharide K
      (KRESTIN((r))): review of development and future perspectives.
AB  - The mechanism of action of protein-bound polysaccharide K (PSK; KRESTIN((r)))
      involves the following actions: (1) recovery from immunosuppression induced by
      humoral factors such as transforming growth factor (TGF)-beta or as a result of
      surgery and chemotherapy; (2) activation of antitumor immune responses including
      maturation of dendritic cells, correction of Th1/Th2 imbalance, and promotion of
      interleukin-15 production by monocytes; and (3) enhancement of the antitumor
      effect of chemotherapy by induction of apoptosis and inhibition of metastasis
      through direct actions on tumor cells. The clinical effectiveness of PSK has been
      demonstrated for various cancers. In patients with gastric or colorectal cancer,
      combined use of PSK with postoperative adjuvant chemotherapy prolongs survival,
      and this effect has been confirmed in multiple meta-analyses. For small-cell lung
      carcinoma, PSK in conjunction with chemotherapy prolongs the remission period. In
      addition, PSK has been shown to be effective against various other cancers,
      reduce the adverse effects of chemotherapy, and improve quality of life. Future
      studies should examine the effects of PSK under different host immune conditions
      and tumor properties, elucidate the mechanism of action exhibited in each
      situation, and identify biomarkers.

PMID- 22139129
TI  - Culture of human mesenchymal stem cells at low oxygen tension improves growth and
      genetic stability by activating glycolysis.
AB  - Expansion of human stem cells before cell therapy is typically performed at 20%
      O(2). Growth in these pro-oxidative conditions can lead to oxidative stress and
      genetic instability. Here, we demonstrate that culture of human mesenchymal stem
      cells at lower, physiological O(2) concentrations significantly increases
      lifespan, limiting oxidative stress, DNA damage, telomere shortening and
      chromosomal aberrations. Our gene expression and bioenergetic data strongly
      suggest that growth at reduced oxygen tensions favors a natural metabolic state
      of increased glycolysis and reduced oxidative phosphorylation. We propose that
      this balance is disturbed at 20% O(2), resulting in abnormally increased levels
      of oxidative stress. These observations indicate that bioenergetic pathways are
      intertwined with the control of lifespan and decisively influence the genetic
      stability of human primary stem cells. We conclude that stem cells for human
      therapy should be grown under low oxygen conditions to increase biosafety.

PMID- 22139130
TI  - An epistatic mini-circuitry between the transcription factors Snail and HNF4alpha
      controls liver stem cell and hepatocyte features exhorting opposite regulation on
      stemness-inhibiting microRNAs.
AB  - Preservation of the epithelial state involves the stable repression of epithelial
      to-mesenchymal transition program, whereas maintenance of the stem compartment
      requires the inhibition of differentiation processes. A simple and direct
      molecular mini-circuitry between master elements of these biological processes
      might provide the best device to keep balanced such complex phenomena. In this
      work, we show that in hepatic stem cell Snail, a transcriptional repressor of the
      hepatocyte differentiation master gene HNF4alpha, directly represses the
      expression of the epithelial microRNAs (miRs)-200c and -34a, which in turn target
      several stem cell genes. Notably, in differentiated hepatocytes HNF4alpha,
      previously identified as a transcriptional repressor of Snail, induces the miRs
      34a and -200a, b, c that, when silenced, causes epithelial dedifferentiation and
      reacquisition of stem traits. Altogether these data unveiled Snail, HNF4alpha and
      miRs-200a, b, c and -34a as epistatic elements controlling hepatic stem cell
      maintenance/differentiation.

PMID- 22139131
TI  - Granzyme K inhibits replication of influenza virus through cleaving the nuclear
      transport complex importin alpha1/beta dimer of infected host cells.
AB  - The influenza A virus is a causative agent of influenza, which infects human
      cells and uses host factors to accomplish viral genome replication as part of its
      life cycle. The nucleoprotein (NP) and PB2 of the influenza virus associate with
      importin alpha1 to gain access to the host nucleus through a ternary import
      complex. Killer cell-mediated cytotoxicity is the primary mechanism of
      eliminating the influenza virus. Here, we showed that lymphokine-activated killer
      cells participated in the elimination of the influenza virus. Granzyme (Gzm) K
      inhibition elevated viral replication in vitro and aggravated viral infection in
      vivo. We identified that importin alpha1 and its transport partner protein
      importin beta are physiological substrates of GzmK. Proteolysis of these two
      substrates wrecked their association to generate the importin alpha1/beta dimer
      and disrupted transportation of viral NP to the nucleus, leading to inhibition of
      influenza virus replication.

PMID- 22139132
TI  - ADF/cofilin proteins translocate to mitochondria during apoptosis but are not
      generally required for cell death signaling.
AB  - Non-muscle cofilin (n-cofilin) is a member of the ADF/cofilin family of actin
      depolymerizing proteins. Recent studies reported a mitochondrial translocation of
      n-cofilin during apoptosis. As these studies also revealed impaired cytochrome c
      release and a block in apoptosis upon small interfering RNA-mediated n-cofilin
      knockdown, n-cofilin was postulated to be essential for apoptosis induction. To
      elucidate the general importance of ADF/cofilin activity for apoptosis, we
      exposed mouse embryonic fibroblasts deficient for n-cofilin, ADF (actin
      depolymerizing factor), or all ADF/cofilin isoforms to well-characterized
      apoptosis inducers. Cytochrome c release, caspase-3 activation, and apoptotic
      chromatin condensation were unchanged in all mutant fibroblasts. Thus, we
      conclude that ADF/cofilin activity is not generally required for induction or
      progression of apoptosis in mammalian cells. Interestingly, mitochondrial
      association of ADF and n-cofilin during apoptosis was preceded by, and dependent
      on, actin that translocated by a yet unknown mechanism to mitochondria during
      cell death.

PMID- 22139133
TI  - FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene
      expression.
AB  - Forkhead transcription factors of the O class (FOXOs) are important targets of
      the phosphatidylinositol 3-kinase/Akt pathway, and are key regulators of the cell
      cycle, apoptosis and response to oxidative stress. FOXOs have been shown to have
      tumour suppressor function and are important for stem cell maintenance. We have
      performed a detailed analysis of the transcriptional programme induced in
      response to Forkhead-box protein O3a (FOXO3a) activation. We observed that FOXO3a
      activation results in the repression of a large number of nuclear-encoded genes
      with mitochondrial function. Repression of these genes was mediated by FOXO3a
      dependent inhibition of c-Myc. FOXO3a activation also caused a reduction in
      mitochondrial DNA copy number, expression of mitochondrial proteins, respiratory
      complexes and mitochondrial respiratory activity. FOXO3a has been previously
      implicated in the detoxification of reactive oxygen species (ROS) through
      induction of manganese-containing superoxide dismutase (SOD2). We observed that
      reduction in ROS levels following FOXO3a activation was independent of SOD2, but
      required c-Myc inhibition. Hypoxia increases ROS production from the
      mitochondria, which is required for stabilisation of the hypoxia-inducible factor
      1alpha (HIF-1alpha). FOXO3a activation blocked the hypoxia-dependent increase in
      ROS and prevented HIF-1alpha stabilisation. Our data suggest that FOXO factors
      regulate mitochondrial activity through inhibition of c-Myc function and alter
      the hypoxia response.

PMID- 22139134
TI  - Antitumor effect of cetuximab in combination with S-1 in EGFR-amplified gastric
      cancer cells.
AB  - Overexpression of human epidermal growth factor receptor (EGFR) has been detected
      in gastric cancer (GC) and is associated with poor outcomes. Combination
      treatment regimens with EGFR-targeting agents and cytotoxic agents are considered
      to be a potential therapeutic option for EGFR-overexpressing GC. Herein, we have
      investigated the effects of combination treatment with the oral fluoropyrimidine
      S-1 and the EGFR-targeting agent cetuximab in GC cells with or without EGFR
      overexpression. EGFR expression was determined by FACS and quantitative PCR in GC
      cells. Experimental 5-fluorouracil (5FU) was used instead of S-1 for in vitro
      experiments. The efficacy of 5FU or cetuximab monotherapy or combination
      5FU/cetuximab therapy was examined in vitro and in vivo. Clinical specimens were
      examined for EGFR by immunohistochemistry (IHC). EGFR expression score was
      defined as strong membrane and cytoplasmic staining in at least 50-75% of cells.
      The combination of 5FU and cetuximab synergistically inhibited cell proliferation
      and exhibited an enhanced proapoptotic effect in GC cells with EGFR
      overexpression. Cetuximab also induced down-regulation of phosphorylation of EGFR
      and AKT, leading to diminished signaling. The antitumor effect of the combination
      of S-1 and cetuximab in vivo was also greater than that of either drug alone. Our
      preclinical findings thus indicate that the combination of S-1 and EGFR-targeting
      therapy is a promising treatment option for GC with EGFR overexpression.

PMID- 22139135
TI  - Recombinant IgE antibodies for passive immunotherapy of solid tumours: from
      concept towards clinical application.
AB  - Therapeutic antibodies have revolutionised treatment of some cancers and improved
      prognosis for many patients. Over half of those available are approved for
      haematological malignancies, but efficacious antibodies for solid tumours are
      still urgently needed. Clinically available antibodies belong to the IgG class,
      the most prevalent antibody class in human blood, while other classes have not
      been extensively considered. We hypothesised that the unique properties of IgE, a
      class of tissue-resident antibodies commonly associated with allergies, which can
      trigger powerful immune responses through strong affinity for their particular
      receptors on effector cells, could be employed for passive immunotherapy of solid
      tumours such as ovarian and breast carcinomas. Our laboratory has examined this
      concept by evaluating two chimaeric antibodies of the same specificity (MOv18)
      but different isotype, an IgG1 and an IgE against the tumour antigen folate
      receptor alpha (FRalpha). The latter demonstrates the potency of IgE to mount
      superior immune responses against tumours in disease-relevant models. We
      identified Fcepsilon receptor-expressing cells, monocytes/macrophages and
      eosinophils, activated by MOv18 IgE to kill tumour cells by mechanisms such as
      ADCC and ADCP. We also applied this notion to a marketed therapeutic, the
      humanised IgG1 antibody trastuzumab and engineered an IgE counterpart, which
      retained the functions of trastuzumab in restricting proliferation of HER2/neu
      expressing tumour cells but also activated effector cells to kill tumour cells by
      different mechanisms. On-going efficacy, safety evaluations and future first-in
      man clinical studies of IgE therapeutics constitute key metrics for this concept,
      providing new scope for antibody immunotherapies for solid tumours.

PMID- 22139136
TI  - IgE and chemotherapy.
AB  - The nexus of chemotherapeutic intervention and the immunomodulation of IgE
      related phenomena are not well understood. The relationship bears importance in
      better understanding the causal and/or resultant effects of one on the other and
      their collective role in the management and sequelae of the cancer patient. This
      review discusses the relationship of chemotherapy on immunoglobulins with a focus
      on IgE and other related biological processes including hypersensitivity
      reactions and proposes models toward effective management of the cancer patient
      in this regard.

PMID- 22139137
TI  - Obstructive sleep apnea syndrome and anthropometric obesity indexes.
AB  - BACKGROUND: The purpose of this study is to investigate whether the general body
      adiposity or regional adiposity was a risk factor in the evolution of obstructive
      sleep apnea syndrome (OSAS) by examining the relationships between the
      anthropometric obesity indexes such as waist (WC) and neck circumference index
      (NC), body mass index (BMI), and OSAS in Turkish adult population, and to access
      the possible differences by gender. METHODS: The data related to
      polysomnographic, demographic, and anthropometric indexes of the 499 subjects
      were examined retrospectively. The patients whose apnea-hypopnea index was >=5
      were determined as OSAS group. RESULTS: The avarage BMI, WC, and NC of the OSAS
      group (n = 431) were statistically higher than the control group (p < 0.001).
      According to logistic regression analysis, BMI, WC, and NC enlargement were
      observed as significant risk factors for OSAS development. Risk coefficients were
      determined 5.53 for NC, 4.48 for WC, and 2.22 for BMI. Cutoff point values for
      anthropometric obesity indexes as OSAS determiner were recorded as below: BMI for
      male >27.77 kg/m(2) and female >28.93 kg/m(2), NC index for male >40 cm and
      female >36 cm, and WC index for male >105 cm and female >101 cm. CONCLUSIONS:
      BMI, WC, and NC enlargement were determined as significant risk factors for OSAS
      development. This was an initial study to determine the cutoff points of which
      increase the OSAS risk in BMI, WC, and NC index in Turkish adult population.

PMID- 22139138
TI  - Effect of automatic versus fixed continuous positive airway pressure for the
      treatment of obstructive sleep apnea: an up-to-date meta-analysis.
AB  - PURPOSE: This study was made to evaluate the effect of automatic continuous
      positive airway pressure (auto-CPAP) versus fixed continuous positive airway
      pressure (fixed CPAP) in reducing the apnea-hypopnea index (AHI) and the mean
      therapy pressure, improving subjective sleepiness, sleep architecture, patient
      compliance, and preference in patients with obstructive sleep apnea. METHODS: We
      searched the electronic databases MEDLINE, EMBASE, the Cochrane Library, and
      Google Scholar. Randomized controlled trials comparing auto-CPAP with fixed CPAP
      were reviewed. Continuous variables were presented as mean difference (MD), and
      dichotomous data as odds ratio (OR), both with 95% confidence intervals (CI).
      RESULTS: We identified 19 studies consisting of 845 patients. Compared to fixed
      CPAP, the use of auto-CPAP reduced mean therapy pressure (MD -1.64; 95% CI -2.46
      to -0.82), improved patient compliance (MD 0.23; 95% CI 0.06 to 0.39), increased
      the percentage of total sleep time (TST) in slow wave sleep (MD 5.11; 95% CI 1.34
      to 8.88), and decreased the percentage of TST in stage 2 sleep (MD -4.75; 95% CI 
      9.38 to -0.11). Moreover, more patients preferred auto-CPAP therapy (OR 3.65; 95%
      CI 1.27 to 10.53). There were nonsignificant trends towards better outcomes with
      auto-CPAP for AHI and Epworth Sleepiness Scale (MD -0.43; 95% CI -1.10 to 0.23,
      and MD -0.24; 95% CI -0.74 to 0.25, respectively), though these are of
      questionable clinical significance. CONCLUSIONS: There are some aspects of
      clinical care, such as a mild improvement in compliance, patient preference, and
      sleep architecture that appear to favor the use of auto-CPAP compared to fixed
      CPAP. The clinical relevance of these findings requires further study.

PMID- 22139139
TI  - Distortion in formalin-fixed brains: using geometric morphometrics to quantify
      the worst-case scenario in mice.
AB  - Although morphometric studies of fixed mammalian brains are an integral part of
      neuroscience, the nature of fixation-related morphometric artifacts is not well
      understood beyond assessments of size changes over fixation time. This study is
      the first to quantitatively co-evaluate the effects of the most common brain
      tissue fixative--formalin--on brain shape, size, and weight, using two
      dimensional landmark analysis of mouse brains fixed in unbuffered, non-saline
      formalin from fresh specimens up to 213 days of preservation. The brains show a
      typical swelling reaction with subsequent decline in size and weight. Weight
      initially under- and later over-estimates size, so that the practice of using
      weight to estimate volume can be problematic. Time to recovery of original size
      resembled that of much larger brained mammals, suggesting that the slow reaction
      of formalin with tissue components mainly determines recovery times. Non-size
      related (anisotropic) distortion of different brain areas accounted for around a
      quarter of overall change suggesting that the use of "all-brain" fixation
      correction factors can introduce considerable error. Distortion occurs mostly
      after the first day of fixation, and extended fixation times impact mostly on
      size, not shape. Fixation effects relatively wider and stouter brain dimensions,
      except the cerebellum whose shape changes less. Evidence from the literature
      suggests that this pattern may be common to mammals due to structural
      commonalities.

PMID- 22139140
TI  - Two non-allelic nuclear genes restore fertility in a gametophytic pattern and
      enhance abiotic stress tolerance in the hybrid rice plant.
AB  - In indica rice, the HongLian (HL)-type combination of cytoplasmic male sterility
      (CMS) and fertility restoration (Rf) is widely used for the production of
      commercial hybrid seeds in China, Laos, Vietnam and other Southeast Asian
      countries. Generally, any member of the gametophytic fertility restoration
      system, 50% of the pollen in hybrid F(1) plants displays recovered sterility. In
      this study, however, a HL-type hybrid variety named HongLian You6 had
      approximately 75% normal (viable) pollen rather than the expected 50%. To resolve
      this discrepancy, several fertility segregation populations, including F(2) and
      BC(1)F(1) derived from the HL-CMS line Yuetai A crossed with the restorer line
      9311, were constructed and subjected to genetic analysis. A gametophytic
      restoration model was discovered to involve two non-allelic nuclear restorer
      genes, Rf5 and Rf6. The Rf5 had been previously identified using a positional
      clone strategy. The Rf6 gene represents a new restorer gene locus, which was
      mapped to the short arm of chromosome 8. The hybrid F(1) plants containing one
      restorer gene, either Rf5 or Rf6, displayed 50% normal pollen grains with I(2)-KI
      solution; however, those with both Rf5 and Rf6 displayed 75% normal pollens. We
      also established that the hybrid F(1) plants including both non-allelic restorer
      genes exhibited an increased stable seed setting when subjected to stress versus
      the F(1) plants with only one restorer gene. Finally, we discuss the breeding
      scheme for the plant gametophytic CMS/Rf system.

PMID- 22139141
TI  - Patient socioeconomic determinants for the choice of the cheapest molecule within
      a cluster: evidence from Belgian prescription data.
AB  - Reference pricing is a common cost-sharing mechanism, with the financial penalty
      for the use of costly drugs shifted from the third-party payer  to the patient.
      Unintended distributional consequences might arise, if the weakest socioeconomic
      groups face a relatively higher financial burden. This study analyzed for a
      sample of Belgian individual prescription data for 4 clusters of commonly used
      drugs (proton pump inhibitors, statins and two groups of antihypertensives [drugs
      acting on renin-angiotensin system and dihydropyridine derivatives]) whether the
      probability to receive the least expensive molecule within a cluster was linked
      to the socioeconomic status of the patient. Logistic regression models included
      individual demographic, working, chronic illness and financial status and small
      area education data for 906,543 prescriptions from 1,280 prescribing general
      practitioners and specialists. For the 4 clusters, results show that patients
      with lower socioeconomic status consistently use slightly more the least
      expensive drugs than other patients. Larger effects are observed for patients
      residing in a nursing home for the elderly, patients entitled to increased
      reimbursement of co-payments, unemployed, patients treated in a primary care
      center financed per capita (and not fee-for-service) and patients having a
      chronic illness. Also, patients residing in neighborhoods with low education
      status use more less expensive drugs. The findings of the study suggest that
      although equity considerations were not explicitly taken into account in the
      design of the reference price system, there is no real equity problem, as the
      costly drugs with supplement are not prescribed more often in patients from lower
      socioeconomic classes.

PMID- 22139142
TI  - Skeletal growth patterns in hereditary multiple exostoses:  a natural history.
AB  - Hereditary multiple exostoses (HME) is a commonly inherited musculoskeletal
      condition and is associated with a diminished stature. We demonstrated that
      adults with HME were significantly shorter when compared with a control group
      (P<0.001); preadolescents, however, were significantly taller than predicted
      (P=0.01). This was reflected by their height centile; 58% of the adults were
      under the 25th centile, whereas 53% of the preadolescence group were above the
      75th centile. Stature was more severely affected in patients with an EXT1
      mutation (P=0.008). This study illustrates a novel age-related growth pattern
      associated with HME, which is also affected by genotype.

PMID- 22139143
TI  - Fabrication of duplex DNA microarrays incorporating methyl-5-cytosine.
AB  - We synthesized customized double-stranded DNA microarrays including methyl-5
      cytosine at CpG dinucleotides and produced all 163,555 possible 8-mers (un-, hemi
      , and di-methylated) to gain insight into how methylation affects transcription
      factor binding. An antibody to methyl-5-cytidine showed greater binding to the
      methylated DNA, demonstrating efficient incorporation of methyl-5-cytosine into
      the synthesized DNA. In contrast, binding of the transcription factor CREB was
      inhibited by CpG methylation. This platform represents a powerful new technology
      to evaluate the effect of DNA methylation on protein binding in any sequence
      context.

PMID- 22139145
TI  - Awake surgery for incidental WHO grade II gliomas involving eloquent areas.
AB  - BACKGROUND: WHO grade II glioma (G2G) is a pre-malignant tumor, usually revealed
      by seizures in young patients living normal lives. G2G grows constantly and will
      inevitably become anaplastic. Surgical resection significantly increases the
      overall survival by delaying malignant transformation. Recently, a similar
      natural history was demonstrated in a patient with incidental G2G, with
      continuous growth and risk of anaplasia. Here, the aim was to study for the first
      time the functional results and extent of resection in a prospective series of
      patients who underwent resection for incidental G2G within eloquent areas.
      METHOD: G2G involving functional regions in the left dominant hemisphere was
      incidentally diagnosed in 11 asymptomatic patients. Resection was achieved in all
      cases after demonstration of a volumetric increase on serial MRIs. Intraoperative
      awake mapping was performed in the 11 patients. FINDINGS: There were no cases of
      mortality or permanent postoperative deficit. A subtotal, total or even
      "supratotal" resection was achieved in the 11 cases, with no partial resections.
      All patients resumed normal social and professional lives, with no seizures (KPS
      100). Due to slow tumor re-growth in three patients with subtotal resection,
      adjuvant chemotherapy was administrated in two cases and radiotherapy in one.
      With a mean follow-up of 40 months since surgery, there was no anaplastic
      transformation. CONCLUSION: These results show that surgery can be considered in
      incidental G2G, even in critical areas, with a minimal risk and optimal
      resection, thanks to intraoperative mapping. Such findings raise the question of
      an early detection.

PMID- 22139144
TI  - Impact of silicon-based quantum dots on the antioxidative system in white muscle
      of Carassius auratus gibelio.
AB  - Silicon-based quantum dots were intraperitoneally injected in individuals of
      Carassius auratus gibelio. Their effects on white muscle were investigated by
      following their distribution and impact on the antioxidative system. The GSH
      level significantly increased after 1 and 3 days of exposure by, respectively,
      85.3 and 25.4%. Seven days later, GSH levels were similar to control
      concentrations. MDA concentration rose after three days by 46.9% and remained at
      the same level after 7 days. Protein thiol levels significantly decreased by 6.7
      and 8.1% after 3 and 7 days, whereas advanced oxidation protein products
      increased by 12.7, respectively, 28.1% in the same time intervals. The protein
      reactive carbonyl groups were raised only after the first day of exposure and
      returned to the control level later on. SOD specific activity increased up to 48%
      after 7 days, while CAT activity increased by 328, 176, and 26% after 1, 3, and 7
      days of treatment. GST specific activity was up-regulated by 87, 18, and 9%,
      while GR activity increased by 68, 34, and 9%. G6PD activity was up-regulated by
      12, 22, and 50%, whereas GPx activity raised by 75 and 109% compared to control
      after, respectively, 1, 3, and 7 days. Our results suggest that oxidative stress
      induced by silicon-based quantum dots was not strong enough to cause permanent
      damage in the white muscle of crucian carp.

PMID- 22139146
TI  - Structures of engineered Clostridium botulinum neurotoxin derivatives.
AB  - Targeted secretion inhibitors (TSIs) are a new class of engineered
      biopharmaceutical molecules derived from the botulinum neurotoxins (BoNTs). They
      consist of the metalloprotease light chain (LC) and translocation domain (Hn) of
      BoNT; they thus lack the native toxicity towards motor neurons but are able to
      target soluble N-ethylmaleimide-sensitive fusion protein attachment receptor
      (SNARE) proteins. These functional fragment (LHn) derivatives are expressed as
      single-chain proteins and require post-translational activation into di-chain
      molecules for function. A range of BoNT derivatives have been produced to
      demonstrate the successful use of engineered SNARE substrate peptides at the LC
      Hn interface that gives these molecules self-activating capabilities.
      Alternatively, recognition sites for specific exoproteases can be engineered to
      allow controlled activation. Here, the crystal structures of three LHn
      derivatives are reported between 2.7 and 3.0 A resolution. Two of these molecules
      are derivatives of serotype A that contain a SNARE peptide. Additionally, a third
      structure corresponds to LHn serotype B that includes peptide linkers at the
      exoprotease activation site. In all three cases the added engineered segments
      could not be modelled owing to disorder. However, these structures highlight the
      strong interactions holding the LHn fold together despite the inclusion of
      significant polypeptide sequences at the LC-Hn interface.

PMID- 22139147
TI  - Structure of hyperthermophilic beta-glucosidase from Pyrococcus furiosus.
AB  - Three categories of cellulases, endoglucanases, cellobiohydrolases and beta
      glucosidases, are commonly used in the process of cellulose saccharification. In
      particular, the activity and characteristics of hyperthermophilic beta
      glucosidase make it promising in industrial applications of biomass. In this
      paper, the crystal structure of the hyperthermophilic beta-glucosidase from
      Pyrococcus furiosus (BGLPf) was determined at 2.35 A resolution in a new crystal
      form. The structure showed that there is one tetramer in the asymmetric unit and
      that the dimeric molecule exhibits a structure that is stable towards sodium
      dodecyl sulfate (SDS). The dimeric molecule migrated in reducing SDS
      polyacrylamide gel electrophoresis (SDS-PAGE) buffer even after boiling at 368 K.
      Energy calculations demonstrated that one of the two dimer interfaces acquired
      the largest solvation free energy. Structural comparison and sequence alignment
      with mesophilic beta-glucosidase A from Clostridium cellulovorans (BGLACc)
      revealed that the elongation at the C-terminal end forms a hydrophobic patch at
      the dimer interface that might contribute to hyperthermostability.

PMID- 22139148
TI  - The 1.7 A resolution structure of At2g44920, a pentapeptide-repeat protein in the
      thylakoid lumen of Arabidopsis thaliana.
AB  - At2g44920 belongs to a diverse family (Pfam PF00805) of pentapeptide-repeat
      proteins (PRPs) that are present in all known organisms except yeast. PRPs
      contain at least eight tandem-repeating sequences of five amino acids with an
      approximate consensus sequence (STAV)(D/N)(L/F)(S/T/R)(X). Recent crystal
      structures show that PRPs adopt a highly regular four-sided right-handed beta
      helical structure consisting mainly of type II and type IV beta-turns, sometimes
      referred to as a repeated five-residue (or Rfr) fold. Among sequenced genomes,
      PRP genes are most abundant in cyanobacteria, leading to speculation that PRPs
      play an important role in the unique lifestyle of photosynthetic cyanobacteria.
      Despite the recent structural characterization of several cyanobacterial PRPs,
      most of their functions remain unknown. Plants, whose chloroplasts are of
      cyanobacterial origin, have only four PRP genes in their genomes. At2g44920 is
      one of three PRPs located in the thylakoid lumen. Here, the crystal structure of
      a double methionine mutant of residues 81-224 of At2g44920, the naturally
      processed fragment of one of its full-length isoforms, is reported at 1.7 A
      resolution. The structure of At2g44920 consists of the characteristic Rfr fold
      with five uninterrupted coils made up of 25 pentapeptide repeats and alpha
      helical elements capping both termini. A disulfide bridge links the two alpha
      helices with a conserved loop between the helical elements at its C-terminus.
      This structure represents the first structure of a PRP protein whose subcellular
      location has been experimentally confirmed to be the thylakoid lumen in a plant
      species.

PMID- 22139149
TI  - Engineered tryptophan in the adenine-binding pocket of catalytic subunit A of A
      ATP synthase demonstrates the importance of aromatic residues in adenine binding,
      forming a tool for steady-state and time-resolved fluorescence spectroscopy.
AB  - A reporter tryptophan residue was individually introduced by site-directed
      mutagenesis into the adenine-binding pocket of the catalytic subunit A (F427W and
      F508W mutants) of the motor protein A(1)A(O) ATP synthase from Pyrococcus
      horikoshii OT3. The crystal structures of the F427W and F508W mutant proteins
      were determined to 2.5 and 2.6 A resolution, respectively. The tryptophan
      substitution caused the fluorescence signal to increase by 28% (F427W) and 33%
      (F508W), with a shift from 333 nm in the wild-type protein to 339 nm in the
      mutant proteins. Tryptophan emission spectra showed binding of Mg-ATP to the
      F427W mutant with a K(d) of 8.5 uM. In contrast, no significant binding of
      nucleotide could be observed for the F508W mutant. A closer inspection of the
      crystal structure of the F427W mutant showed that the adenine-binding pocket had
      widened by 0.7 A (to 8.70 A) in comparison to the wild-type subunit A (8.07 A)
      owing to tryptophan substitution, as a result of which it was able to bind ATP.
      In contrast, the adenine-binding pocket had narrowed in the F508W mutant. The two
      mutants presented demonstrate that the exact volume of the adenine ribose binding
      pocket is essential for nucleotide binding and even minor narrowing makes it
      unfit for nucleotide binding. In addition, structural and fluorescence data
      confirmed the viability of the fluorescently active mutant F427W, which had ideal
      tryptophan spectra for future structure-based time-resolved dynamic measurements
      of the catalytic subunit A of the ATP-synthesizing enzyme A-ATP synthase.

PMID- 22139150
TI  - Therapeutic target-site variability in alpha1-antitrypsin characterized at high
      resolution.
AB  - The intrinsic propensity of alpha(1)-antitrypsin to undergo conformational
      transitions from its metastable native state to hyperstable forms provides a
      motive force for its antiprotease function. However, aberrant conformational
      change can also occur via an intermolecular linkage that results in
      polymerization. This has both loss-of-function and gain-of-function effects that
      lead to deficiency of the protein in human circulation, emphysema and hepatic
      cirrhosis. One of the most promising therapeutic strategies being developed to
      treat this disease targets small molecules to an allosteric site in the alpha(1)
      antitrypsin molecule. Partial filling of this site impedes polymerization without
      abolishing function. Drug development can be improved by optimizing data on the
      structure and dynamics of this site. A new 1.8 A resolution structure of alpha(1)
      antitrypsin demonstrates structural variability within this site, with associated
      fluctuations in its upper and lower entrance grooves and ligand-binding
      characteristics around the innermost stable enclosed hydrophobic recess. These
      data will allow a broader selection of chemotypes and derivatives to be tested in
      silico and in vitro when screening and developing compounds to modulate
      conformational change to block the pathological mechanism while preserving
      function.

PMID- 22139151
TI  - A 1.5 A resolution X-ray structure of the catalytic module of
      Caldicellulosiruptor bescii family 3 pectate lyase.
AB  - A 1.5 A resolution X-ray structure of the catalytic module of
      Caldicellulosiruptor bescii family 3 pectate lyase is reported (PDB entry 3t9g).
      The resulting structure was refined to an R factor of 0.143 and an R(free) of
      0.178. Structural analysis shows that this new structure is very similar to the
      previously solved structure of a family 3 pectate lyase from Bacillus sp. strain
      KSM-P15 (PDB entry 1ee6), with a root-mean-square deviation of 0.93 A and a
      sequence identity of 53%. This structural similarity is significant considering
      that C. bescii is a hyperthermophile and Bacillus sp. is a mesophile.

PMID- 22139152
TI  - The structure of LsrB from Yersinia pestis complexed with autoinducer-2.
AB  - The crystal structure of LsrB from Yersinia pestis complexed with autoinducer-2
      (AI-2; space group P2(1)2(1)2(1), unit-cell parameters a = 40.61, b = 61.03, c =
      125.23 A) has been solved by molecular replacement using the structure of LsrB
      from Salmonella typhimurium (PDB entry 1tjy) and refined to R = 0.180 (R(free) =
      0.213) at 1.75 A resolution. The electron density for bound AI-2 and the
      stereochemistry of the AI-2-binding site are consistent with bound AI-2 adopting
      the (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran conformation, just as
      has been observed in the crystal structures of the Salmonella typhimurium and
      Sinorhizobium meliloti LsrB-AI-2 complexes.

PMID- 22139153
TI  - Structure of d(CGGGTACCCG)4 as a four-way Holliday junction.
AB  - The crystal structure of the decamer sequence d(CGGGTACCCG)(4) as a four-way
      Holliday junction has been determined at 2.35 A resolution. The sequence was
      designed in order to understand the principles that govern the relationship
      between sequence and branching structure. It crystallized as a four-way junction
      structure with an overall geometry similar to those of previously determined
      Holliday junction structures.

PMID- 22139154
TI  - The structure of an N11A mutant of the G-protein domain of FeoB.
AB  - The uptake of ferrous iron in prokaryotes is mediated by the G-protein-coupled
      membrane protein FeoB. The protein contains two N-terminal soluble domains that
      are together called 'NFeoB'. One of these is a G-protein domain, and GTP
      hydrolysis by this domain is essential for iron transport. The GTPase activity of
      NFeoB is accelerated in the presence of potassium ions, which bind at a site
      adjacent to the nucleotide. One of the ligands at the potassium-binding site is a
      conserved asparagine residue, which corresponds to Asn11 in Streptococcus
      thermophilus NFeoB. The structure of an N11A S. thermophilus NFeoB mutant has
      been determined and refined to a resolution of 1.85 A; the crystals contained a
      mixture of mant-GDP-bound and mant-GMP-bound protein. The structure demonstrates
      how the use of a derivatized nucleotide in cocrystallization experiments can
      facilitate the growth of diffraction-quality crystals.

PMID- 22139155
TI  - Crystallization and preliminary X-ray structure analysis of human ribosomal
      protein L30e.
AB  - Many functions have been reported for the eukaryotic ribosomal protein L30e. L30e
      makes several inter-subunit and intra-subunit interactions with protein or RNA
      components of the 80S ribosome. Yeast L30e has been shown to bind to its own
      transcript to autoregulate expression at both the transcriptional and the
      translational levels. Furthermore, it has been reported that mammalian L30e is a
      component of the selenocysteine-incorporation machinery by binding to the
      selenocysteine-insertion sequence on mRNA. As high-resolution crystal structures
      of mammalian L30e are not available, the purification, crystallization and X-ray
      structure analysis of human L30e are presented here.

PMID- 22139156
TI  - Structure of the H107R variant of the extracellular domain of mouse NKR-P1A at
      2.3 A resolution.
AB  - The structure of the H107R variant of the extracellular domain of the mouse
      natural killer cell receptor NKR-P1A has been determined by X-ray diffraction at
      2.3 A resolution from a merohedrally twinned crystal. Unlike the structure of the
      wild-type receptor in space group I4(1)22 with a single chain per asymmetric
      unit, the crystals of the variant belonged to space group I4(1) with a dimer in
      the asymmetric unit. Different degrees of merohedral twinning were detected in
      five data sets collected from different crystals. The mutation does not have a
      significant impact on the overall structure, but led to the binding of an
      additional phosphate ion at the interface of the molecules.

PMID- 22139158
TI  - Overexpression, purification, crystallization and preliminary X-ray
      crystallographic analysis of the periplasmic domain of outer membrane protein A
      from Acinetobacter baumannii.
AB  - Outer membrane protein A from Acinetobacter baumannii (AbOmpA) is a major outer
      membrane protein and a key player in the bacterial pathogenesis that induces host
      cell death. AbOmpA is presumed to consist of an N-terminal beta-barrel
      transmembrane domain and a C-terminal periplasmic OmpA-like domain. In this
      study, the recombinant C-terminal periplasmic domain of AbOmpA was overexpressed
      in Escherichia coli, purified and crystallized using the vapour-diffusion method.
      A native diffraction data set was collected to a resolution of 2.0 A using
      synchrotron radiation. The space group of the crystal was P2(1), with unit-cell
      parameters a = 58.24, b = 98.59, c = 97.96 A, beta = 105.92 degrees . The native
      crystal contained seven or eight molecules per asymmetric unit and had a
      calculated Matthews coefficient of 2.93 or 2.56 A(3) Da(-1).

PMID- 22139157
TI  - Structure of the fucose mutarotase from Streptococcus pneumoniae in complex with
      L-fucose.
AB  - Streptococcus pneumoniae relies on a variety of carbohydrate-utilization pathways
      for both colonization of its human host and full virulence during the development
      of invasive disease. One such pathway is the fucose-utilization pathway, a
      component of which is fucose mutarotase (SpFcsU), an enzyme that performs the
      interconversion between alpha-L-fucose and beta-L-fucose. This protein was
      crystallized and its three-dimensional structure was solved in complex with L
      fucose. The structure shows a complex decameric quaternary structure with a high
      overall degree of structural identity to Escherichia coli FcsU (EcFcsU).
      Furthermore, the active-site architecture of SpFcsU is highly similar to that of
      EcFcsU. When considered in the context of the fucose-utilization pathway found in
      S. pneumoniae, SpFcsU appears to link the two halves of the pathway by enhancing
      the rate of conversion of the product of the final glycoside hydrolysis step,
      beta-fucose, into the substrate for the fucose isomerase, alpha-fucose.

PMID- 22139159
TI  - Purification, crystallization and preliminary X-ray characterization of a
      haemagglutinin from the seeds of Jatropha curcas.
AB  - The plant Jatropha curcas (Euphorbiaceae) is an important source of biofuel from
      the inedible oil present in its toxic seeds. The toxicity arises from the
      presence of curcin, a ribosome-inactivating protein showing haemagglutination
      activity. In this communication, the purification, crystallization and
      preliminary X-ray characterization are reported of a small protein isolated from
      J. curcas seeds with a molecular mass of ~10 kDa that agglutinates rabbit
      erythrocytes. The protein was crystallized using the hanging-drop vapour
      diffusion method and also by the microbatch method in 72-well HLA plates, using
      PEG 8000 as the precipitant in both conditions. X-ray diffraction data collected
      from the rod-shaped crystals were processed in the orthorhombic space group
      P2(1)2(1)2(1). The crystals diffracted to 2.8 A resolution at 103 K.

PMID- 22139160
TI  - Cloning, expression, purification and crystallization of dihydrodipicolinate
      synthase from the grapevine Vitis vinifera.
AB  - Dihydrodipicolinate synthase (DHDPS) catalyses the first committed step of the
      lysine-biosynthesis pathway in bacteria, plants and some fungi. This study
      describes the cloning, expression, purification and crystallization of DHDPS from
      the grapevine Vitis vinifera (Vv-DHDPS). Following in-drop cleavage of the
      hexahistidine tag, cocrystals of Vv-DHDPS with the substrate pyruvate were grown
      in 0.1 M Bis-Tris propane pH 8.2, 0.2 M sodium bromide, 20%(w/v) PEG 3350. X-ray
      diffraction data in space group P1 at a resolution of 2.2 A are presented.
      Preliminary diffraction data analysis indicated the presence of eight molecules
      per asymmetric unit (V(M) = 2.55 A(3) Da(-1), 52% solvent content). The pending
      crystal structure of Vv-DHDPS will provide insight into the molecular evolution
      in quaternary structure of DHDPS enzymes.

PMID- 22139161
TI  - Crystallization and preliminary crystallographic analysis of dextranase from
      Streptococcus mutans.
AB  - Streptococcus mutans dextranase hydrolyzes the internal alpha-1,6-linkages of
      dextran and belongs to glycoside hydrolase family 66. An N- and C-terminal
      deletion mutant of S. mutans dextranase was crystallized by the sitting-drop
      vapour-diffusion method. The crystals diffracted to a resolution of 1.6 A and
      belonged to space group P2(1), with unit-cell parameters a = 53.2, b = 89.7, c =
      63.3 A, beta = 102.3 degrees . Assuming that the asymmetric unit of the crystal
      contained one molecule, the Matthews coefficient was calculated to be 4.07 A(3)
      Da(-1); assuming the presence of two molecules in the asymmetric unit it was
      calculated to be 2.03 A(3) Da(-1).

PMID- 22139162
TI  - Crystallization and preliminary X-ray analysis of crinumin, a chymotrypsin-like
      glycosylated serine protease with thrombolytic and antiplatelet activity.
AB  - Crinumin, a novel glycosylated serine protease with chymotrypsin-like catalytic
      specificity, was purified from the medicinally important plant Crinum asiaticum.
      Crinumin is a 67.7 kDa protease with an extraordinary stability and activity over
      a wide range of pH and temperature and is functional in aqueous, organic and
      chaotropic solutions. The purified protease has thrombolytic and antiplatelet
      activity. The use of C. asiaticum extracts has also been reported for the
      treatment of a variety of disorders such as injury, joint inflammation and
      arthritis. In order to understand its structure-function relationship, the enzyme
      was purified from the plant latex and crystallized by the hanging-drop vapour
      diffusion method. X-ray diffraction data were collected from a single crystal and
      processed to 2.8 A resolution. The crystal belonged to the monoclinic space group
      C2, with unit-cell parameters a = 121.61, b = 95.00, c = 72.10 A, alpha = gamma =
      90, beta = 114.19 degrees . The Matthews coefficient was 2.81 A(3) Da(-1),
      corresponding to a solvent content of 56%, assuming one molecule in the
      asymmetric unit. Structure determination of the enzyme is in progress.

PMID- 22139163
TI  - Crystallization and preliminary X-ray crystallographic analysis of beta-ketoacyl
      ACP synthase I (XoFabB) from Xanthomonas oryzae pv. oryzae.
AB  - The proteins in the fatty-acid synthesis pathway in bacteria have significant
      potential as targets for the development of antibacterial agents. An essential
      elongation step in fatty-acid synthesis is performed by beta-ketoacyl-acyl
      carrier protein synthase I (FabB). The organism Xanthomonas oryzae pv. oryzae
      (Xoo) causes a destructive bacterial blight disease of rice. The XoFabB protein
      from Xoo was expressed, purified and crystallized for the three-dimensional
      structure determination that is essential for the development of specific
      inhibitors of the enzyme. An XoFabB crystal diffracted to 3.0 A resolution and
      belonged to the tetragonal space group P4(1), with unit-cell parameters a = b =
      82.2, c = 233.2 A. Assuming that the crystallographic structure contains four
      molecules in the asymmetric unit, the corresponding V(M) would be 2.18 A(3) Da(
      1) and the solvent content would be 43.5%. The initial structure was determined
      by the MOLREP program with an R factor of 44.0% and does contain four monomers in
      the asymmetric unit.

PMID- 22139164
TI  - Overexpression, purification, crystallization and preliminary crystallographic
      studies of a hyperthermophilic adenylosuccinate synthetase from Pyrococcus
      horikoshii OT3.
AB  - Adenylosuccinate synthetase (AdSS) is a ubiquitous enzyme that catalyzes the
      first committed step in the conversion of inosine monophosphate (IMP) to
      adenosine monophosphate (AMP) in the purine-biosynthetic pathway. Although AdSS
      from the vast majority of organisms is 430-457 amino acids in length, AdSS
      sequences isolated from thermophilic archaea are 90-120 amino acids shorter. In
      this study, crystallographic studies of a short AdSS sequence from Pyrococcus
      horikoshii OT3 (PhAdSS) were performed in order to reveal the unusual structure
      of AdSS from thermophilic archaea. Crystals of PhAdSS were obtained by the
      microbatch-under-oil method and X-ray diffraction data were collected to 2.50 A
      resolution. The crystal belonged to the trigonal space group P3(2)12, with unit
      cell parameters a = b = 57.2, c = 107.9 A. There was one molecule per asymmetric
      unit, giving a Matthews coefficient of 2.17 A(3) Da(-1) and an approximate
      solvent content of 43%. In contrast, the results of native polyacrylamide gel
      electrophoresis and analytical ultracentrifugation showed that the recombinant
      PhAdSS formed a dimer in solution.

PMID- 22139165
TI  - Overexpression, crystallization and preliminary X-ray crystallographic analysis
      of shikimate dehydrogenase from Archaeoglobus fulgidus.
AB  - Shikimate dehydrogenase (SDH), which catalyses the NADPH-dependent reduction of 3
      dehydroshikimate to shikimate in the shikimate pathway, is an attractive target
      for the development of herbicides and antimicrobial agents. Previous structural
      studies have shown that SDH exists in two conformations, an open and a closed
      form, and it is believed that the conformational state is crucial to
      understanding its catalytic mechanism. In order to facilitate further structural
      comparisons among SDHs, including the conformational state, structural analysis
      of an SDH from Archaeoglobus fulgidus encoded by the Af2327 gene has been
      initiated. SeMet-labelled SDH from A. fulgidus was overexpressed in Escherichia
      coli and crystallized at 296 K using ammonium sulfate as a precipitant in order
      to use the MAD method for structure determination. Crystals of A. fulgidus SDH
      grown in the presence of NADP(+) diffracted to 2.8 A resolution and belonged to
      the trigonal space group P3(2)21 (or P3(2)21), with unit-cell parameters a =
      111.3, b = 111.3, c = 76.2 A. Three diffraction data sets were collected. The
      asymmetric unit contains two monomers, with a corresponding V(M) of 2.34 A(3) Da(
      1) and a solvent content of 47% by volume.

PMID- 22139166
TI  - Crystallization and preliminary crystallographic analysis of a putative
      glucokinase/hexokinase from Thermus thermophilus.
AB  - Glucokinase/hexokinase catalyzes the phosphorylation of glucose to glucose 6
      phosphate, which is the first step of glycolysis. The open reading frame TTHA0299
      of the extreme thermophile Thermus thermophilus encodes a putative
      glucokinase/hexokinase which contains the consensus sequence for proteins from
      the repressors, open reading frames and sugar kinases family. In this study, the
      glucokinase/hexokinase from T. thermophilus was purified and crystallized using
      polyethylene glycol 8000 as a precipitant. Diffraction data were collected and
      processed to 2.02 A resolution. The crystal belonged to space group P2(1), with
      unit-cell parameters a = 70.93, b = 138.14, c = 75.16 A, beta = 95.41 degrees .

PMID- 22139167
TI  - Crystallization and preliminary X-ray crystallographic studies of VibE, a
      vibriobactin-specific 2,3-dihydroxybenzoate-AMP ligase from Vibrio cholerae.
AB  - Vibriobactin synthetases (VibABCDEFH) catalyze the biosynthesis of vibriobactin
      in the pathogenic bacterium Vibrio cholerae. VibE, a vibriobactin-specific 2,3
      dihydroxybenzoate-AMP ligase, plays a critical role in the transfer of 2,3
      dihydroxybenzoate to the aryl carrier protein domain of holo VibB. Here, the
      cloning, protein expression and purification, crystallization and preliminary X
      ray crystallographic analysis of VibE from V. cholerae are reported. The VibE
      crystal diffracted to 2.3 A resolution. The crystal belonged to space group
      P2(1), with unit-cell parameters a = 56.471, b = 45.927, c = 77.014 A, beta =
      95.895 degrees . There is one protein molecule in the asymmetric unit, with a
      corresponding Matthews coefficient of 1.63 A(3) Da(-1) and solvent content of
      24.41%.

PMID- 22139168
TI  - Crystallization and preliminary X-ray analysis of peptidyl-tRNA hydrolase from
      Escherichia coli in complex with the acceptor-TPsiC domain of tRNA.
AB  - Peptidyl-tRNA hydrolase (Pth) cleaves the ester bond between the peptide and the
      tRNA of peptidyl-tRNA molecules, which are the product of aborted translation. In
      the present work, Pth from Escherichia coli was crystallized with the acceptor
      TPsiC domain of tRNA using 1,4-butanediol as a precipitant. The crystals belonged
      to the hexagonal space group P6(1), with unit-cell parameters a = b = 55.1, c =
      413.1 A, and diffracted X-rays beyond 2.4 A resolution. The asymmetric unit is
      expected to contain two complexes of Pth and the acceptor-TPsiC domain of tRNA
      (V(M) = 2.8 A(3) Da(-1)), with a solvent content of 60.8%. The structure is being
      solved by molecular replacement.

PMID- 22139169
TI  - Improved X-ray diffraction from Bacillus megaterium penicillin G acylase crystals
      through long cryosoaking dehydration.
AB  - Penicillin G acylase from Bacillus megaterium (BmPGA) is currently used in the
      pharmaceutical industry as an alternative to PGA from Escherichia coli (EcPGA)
      for the hydrolysis of penicillin G to produce 6-aminopenicillanic acid (6-APA), a
      penam nucleus for semisynthetic penicillins. Despite the significant differences
      in amino-acid sequence between PGAs from Gram-positive and Gram-negative
      bacteria, a representative PGA structure of Gram-positive origin has never been
      reported. In this study, crystallization and diffraction studies of BmPGA are
      described. Poor diffraction patterns with blurred spots at higher resolution were
      typical for BmPGA crystals cryocooled after a brief immersion in cryoprotectant
      solution. Overnight soaking in the same cryo-solution substantially improved both
      the mosaicity and resolution limit through the establishment of a new crystal
      packing equilibrium. A crystal of BmPGA diffracted X-rays to 2.20 A resolution
      and belonged to the monoclinic space group P2(1) with one molecule of BmPGA in
      the asymmetric unit.

PMID- 22139170
TI  - Crystallization and preliminary crystallographic analysis of a C2 protein from
      Arabidopsis thaliana.
AB  - An uncharacterized protein from Arabidopsis thaliana consisting of a single C2
      domain (At3g17980) was cloned into the pETM11 vector and expressed in Escherichia
      coli, allowing purification to homogeneity in a single chromatographic step. Good
      quality diffracting crystals were obtained using vapour-diffusion techniques. The
      crystals diffracted to 2.2 A resolution and belonged to space group
      P2(1)2(1)2(1), with unit-cell parameters a = 35.3, b = 88.9, c = 110.6 A. A
      promising molecular-replacement solution has been found using the structure of
      the C2 domain of Munc13-C2b (PDB entry 3kwt) as the search model.

PMID- 22139171
TI  - Crystallization and preliminary crystallographic studies of the NAD+-dependent
      deacetylase HST1 from Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae NAD(+)-dependent deacetylase HST1 belongs to the
      class III HDAC family; it acts as a transcriptional corepressor for the specific
      middle sporulation and de novo NAD(+)-biosynthesis genes and also takes part in
      the SET3C and SUM1-RFM1-HST1 complexes. Structural information on HST1 and its
      related complexes would be helpful in order to understand the structural basis of
      its deacetylation mechanism and the assembly of these complexes. Here, HST1(156
      503) was expressed and crystallized. Crystals grown by the hanging-drop vapour
      diffusion method diffracted to 2.90 A resolution and belonged to space group
      P2(1), with unit-cell parameters a = 40.2, b = 101.7, c = 43.9 A, beta = 103.9
      degrees . Both Matthews coefficient analysis and the self-rotation function
      suggested the presence of four molecules per asymmetric unit in the crystal, with
      a solvent content of 49.76% (V(M) = 2.45 A(3) Da(-1)).

PMID- 22139172
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      studies of the human keratin 4-binding domain of serine-rich repeat protein 1
      from Streptococcus agalactiae.
AB  - Serine-rich repeat protein 1 (Srr-1) is a surface protein from Streptococcus
      agalactiae. A 17 kDa region of this protein has been identified to bind to human
      keratin 4 (K4) and is termed the Srr-1 K4-binding domain (Srr-1-K4BD).
      Recombinant Srr-1-K4BD was overexpressed in Escherichia coli BL21 (DE3) cells.
      Native and selenomethionine-substituted proteins were prepared using Luria
      Bertani (LB) and M9 minimal media, respectively. A two-step purification protocol
      was carried out to obtain a final homogenous sample of Srr-1-K4BD. Crystals of
      native Srr-1-K4BD were obtained using PEG 3350 as a precipitant. The crystals
      diffracted to 3.8 A resolution using synchrotron radiation and belonged to space
      group P2(1), with unit-cell parameters a = 47.56, b = 59.48, c = 94.71 A, beta =
      93.95 degrees .

PMID- 22139173
TI  - Crystallization and preliminary X-ray analysis of crustacean hyperglycaemic
      hormone from the kuruma prawn Marsupenaeus japonicus in its weakly active
      precursor form.
AB  - Crustacean hyperglycaemic hormone (CHH) plays a pivotal role in the regulation of
      glucose metabolism in crustaceans. Pej-SGP-I, one of the six known CHHs in the
      kuruma prawn Marsupenaeus japonicus, was heterologously expressed in Escherichia
      coli as an N-terminally His-tagged and Nus-tagged protein in its weakly active
      precursor form, Pej-SGP-I-Gly, which has an extra glycine residue at the C
      terminus. The recombinant peptide was subjected to affinity purification, tag
      removal, further purification and crystallization by the sitting-drop vapour
      diffusion method using NaCl as the main precipitant. The crystals diffracted to
      1.95 A resolution and the space group was assigned as primitive orthorhombic
      P2(1)2(1)2(1), with unit-cell parameters a = 40.19, b = 53.65, c = 53.63 A. The
      Matthews coefficient (V(M) = 1.73 A(3) Da(-1)) indicated that the crystal
      contained two Pej-SGP-I-Gly molecules per asymmetric unit, with a solvent content
      of 29.0%.

PMID- 22139174
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      crystallographic study of PurH from Escherichia coli.
AB  - In bacteria and eukaryotes, the last two steps of de novo purine biosynthesis are
      catalyzed by bifunctional purine-biosynthesis protein (PurH), which is composed
      of two functionally independent domains linked by a flexible region. The N
      terminal domain possesses IMP cyclohydrolase activity and the C-terminal domain
      possesses aminoimidazole-4-carboxamide ribonucleotide transformylase activity.
      This study reports the expression, purification, crystallization and preliminary
      X-ray crystallographic analysis of PurH from Escherichia coli with an N-terminal
      His(6) tag. The crystals diffracted to a maximum resolution of 3.05 A and
      belonged to the monoclinic space group P2(1), with unit-cell parameters a =
      76.37, b = 132.15, c = 82.64 A, beta = 111.86 degrees .

PMID- 22139175
TI  - Thermostable multicopper oxidase from Thermus thermophilus HB27: crystallization
      and preliminary X-ray diffraction analysis of apo and holo forms.
AB  - A thermostable multicopper oxidase from Thermus thermophilus HB27 (Tth-MCO) was
      successfully crystallized using the sitting-drop and hanging-drop vapour
      diffusion methods. Crystallization conditions and preliminary X-ray diffraction
      data to 1.5 A resolution obtained using synchrotron radiation at 100 K are
      reported. The crystals belonged to space group C222(1), with unit-cell parameters
      a = 93.6, b = 110.3, c = 96.3 A. A monomer in the asymmetric unit yielded a
      Matthews coefficient (V(M)) of 2.60 A(3) Da(-1) and a solvent content of 53%. An
      inactive enzyme form, apo-Tth-MCO, was also crystallized and diffraction data
      were collected to 1.7 A resolution. In addition, a second inactive form of the
      enzyme, Hg-Tth-MCO, was obtained by soaking apo-Tth-MCO crystals with mercury(II)
      chloride and data were collected to a resolution of 1.7 A.

PMID- 22139176
TI  - Crystallization of Chlorella deoxyuridine triphosphatase.
AB  - Deoxyuridine triphosphatase (dUTPase) is a ubiquitous enzyme that has been widely
      studied owing to its function and evolutionary significance. The gene coding for
      the dUTPase from the Chlorella alga was codon-optimized and synthesized. The
      synthetic gene was expressed in Escherichia coli and recombinant core Chlorella
      dUTPase (chdUTPase) was purified. Crystallization of chdUTPase was performed by
      the repetitive hanging-drop vapor-diffusion method at 298 K with ammonium sulfate
      as the precipitant. In the presence of 2'-deoxyuridine-5'-[(alpha,beta)
      imido]triphosphate and magnesium, the enzyme produced die-shaped hexagonal R3
      crystals with unit-cell parameters a = b = 66.9, c = 93.6 A, gamma = 120 degrees
      . X-ray diffraction data for chdUTPase were collected to 1.6 A resolution. The
      crystallization of chdUTPase with manganese resulted in very fragile clusters of
      needles.

PMID- 22139177
TI  - Crystallization and X-ray diffraction analysis of the C-terminal domain of the
      flax rust effector protein AvrM.
AB  - The flax rust effector AvrM is a secreted protein of unknown fold that is
      recognized by the M resistance protein in flax. In order to investigate the
      structural basis of the AvrM-M interaction and possible virulence-associated
      functions of AvrM, the C-terminal domains of two different AvrM variants (AvrM-A
      and avrM) were crystallized. Crystals of native AvrM-A were obtained using
      pentaerythritol ethoxylate (15/4 EO/OH) as a precipitant and diffracted X-rays to
      2.9 A resolution. Selenomethionine-derivative crystals of similar quality were
      obtained using PEG 1500 as a precipitant. Both the native and selenomethionine
      labelled AvrM-A crystals had symmetry of space group C222(1) with eight molecules
      in the asymmetric unit. Crystals of avrM had symmetry of space group
      P2(1)2(1)2(1) and diffracted X-rays to 2.7 A resolution. Initial AvrM-A phases
      were calculated using the single-wavelength anomalous dispersion (SAD) method and
      a partial model was built. Phases for avrM were obtained by molecular replacement
      using the partial AvrM-A model.

PMID- 22139178
TI  - Crystallization and preliminary X-ray diffraction analysis of Val57 mutants of
      the amyloidogenic protein human cystatin C.
AB  - Human cystatin C (hCC) is a low-molecular-mass protein (120 amino-acid residues,
      13 343 Da) found in all nucleated cells. Its main physiological role is
      regulation of the activity of cysteine proteases. Biologically active hCC is a
      monomeric protein, but all crystallization efforts have resulted in a dimeric
      domain-swapped structure. Recently, two monomeric structures were reported for
      cystatin C variants. In one of them stabilization was achieved by abolishing the
      possibility of domain swapping by the introduction of an additional disulfide
      bridge connecting the two protein domains (Cys47-Cys69). In the second structure,
      reported by this group, the monomeric hCC fold was preserved by stabilization of
      the conformationally constrained loop (L1) by a single-amino-acid substitution
      (V57N). To further assess the influence of changes in the sequence and properties
      of loop L1 on the dimerization propensity of cystatin C, two additional hCC
      mutants were obtained: one with a residue favoured in beta-turns (V57D) and
      another with proline (V57P), a residue that is known to be a structural element
      that can rigidify but also broaden turns. Here, the expression, purification and
      crystallization of V57D and V57P variants of recombinant human cystatin C are
      described. Crystals were grown by the vapour-diffusion method. Several
      diffraction data sets were collected using a synchrotron source at the Advanced
      Photon Source, Argonne National Laboratory, Chicago, USA.

PMID- 22139179
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      diffraction studies of a major group 7 allergen, Der f 7, from the dust mite
      Dermatophagoides farinae.
AB  - Der f 7 is a major group 7 allergen from the dust mite Dermatophagoides farinae
      that shows 86% sequence identity to the homologous allergen Der p 7 from D.
      pteronyssinus. Der f 7 was successfully overexpressed in an Escherichia coli
      expression system and purified to homogeneity using Ni-NTA affinity and size
      exclusion column chromatography. SeMet-labelled Der f 7 was crystallized by the
      hanging-drop vapour-diffusion method using a reservoir solution consisting of 0.1
      M bis-tris pH 7.4 and 28% polyethylene glycol monomethyl ether 2000 at 293 K. X
      ray diffraction data were collected to 2.24 A resolution using synchrotron
      radiation. The crystals belonged to the orthorhombic system, space group
      P2(1)2(1)2(1), with unit-cell parameters a = 50.19, b = 58.67, c = 123.81 A.
      Based on the estimated Matthews coefficient (2.16 A(3) Da(-1)), two molecules of
      Der f 7 could be present in the asymmetric unit of the crystal lattice.

PMID- 22139180
TI  - Purification, crystallization and preliminary X-ray diffraction studies of the
      arsenic repressor ArsR from Corynebacterium glutamicum.
AB  - ArsR is a member of the SmtB/ArsR family of metalloregulatory proteins that
      regulate prokaryotic arsenic-resistance operons. Here, the crystallization and
      preliminary X-ray diffraction studies of a cysteine-free derivative of ArsR from
      Corynebacterium glutamicum (CgArsR-C15/16/55S) are reported. CgArsR-C15/16/55S
      was expressed, purified, crystallized and X-ray diffraction data were collected
      to 1.86 A resolution. The protein crystallized in a tetragonal space group (P4),
      with unit-cell parameters a = b = 41.84, c = 99.47 A.

PMID- 22139181
TI  - Crystallization and X-ray data collection of HP0902 from Helicobacter pylori
      26695.
AB  - HP0902 from Helicobacter pylori 26695 belongs to the cupin superfamily of
      proteins, which encompasses proteins with a great diversity in function. In this
      work, two types of recombinant HP0902 protein were crystallized: one with an N
      terminal His(6) tag ((H6)HP0902) and the other with a C-terminal His(6) tag
      (HP0902(H6)). The (H6)HP0902 crystal diffracted to 1.40 A resolution and belonged
      to space group P2(1), with unit-cell parameters a = 33.5, b = 78.6, c = 41.4 A.
      The HP0902(H6) crystal belonged to space group P4(3)2(1)2 or P4(1)2(1)2 and
      diffracted to 2.5 A resolution, with unit-cell parameters a = b = 50.4, c = 142.0
      A.

PMID- 22139182
TI  - Cloning, purification and crystallographic analysis of a hypothetical protein,
      BPSL1549, from Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei BPSL1549, a putative protein of unknown function, has
      been overexpressed in Escherichia coli, purified and subsequently crystallized by
      the hanging-drop vapour-diffusion method using PEG as a precipitant to give
      crystals with overall dimensions of 0.15 * 0.15 * 0.1 mm. Native data were
      collected to 1.47 A resolution at the European Synchrotron Radiation Facility
      (ESRF). The crystals belonged to space group P2(1)2(1)2(1), with unit-cell
      parameters a = 37.1, b = 45.4, c = 111.9 A and with a single polypeptide chain in
      the asymmetric unit.

PMID- 22139183
TI  - Purification, crystallization and preliminary X-ray diffraction of fluorescence
      recovery protein from Synechocystis PCC 6803.
AB  - Fluorescence recovery protein (FRP), which is encoded by the slr1964 gene in
      Synechocystis PCC 6803, plays a key role in the orange carotenoid protein-related
      photoprotective mechanism in cyanobacteria. As the crystal structure of FRP may
      provide information about the biological functions and mechanism of action of the
      protein, recombinant full-length FRP and a truncated form were overexpressed,
      purified and crystallized at 291 K using ethylene imine polymer as the
      precipitant. An FRP data set was collected to a resolution of 2.75 A at low
      temperature (100 K). The crystal belonged to space group P4(1)2(1)2, with unit
      cell parameters a = b = 61.9, c = 160.7 A, alpha = beta = gamma = 90 degrees .
      Assuming that the asymmetric unit contains three molecules, the Matthews
      coefficient was calculated to be 2.1 A(3) Da(-1).

PMID- 22139184
TI  - Crystallization and preliminary X-ray diffraction analysis of mouse prostaglandin
      F2alpha synthase, AKR1B3.
AB  - Aldo-keto reductase 1B3 (AKR1B3) catalyzes the NADPH-dependent reduction of
      prostaglandin H(2) (PGH(2)), which is a common intermediate of various
      prostanoids, to form PGF(2alpha). AKR1B3 also reduces PGH(2) to PGD(2) in the
      absence of NADPH. AKR1B3 produced in Escherichia coli was crystallized in complex
      with NADPH by the sitting-drop vapour-diffusion method. The crystal was
      tetragonal, belonging to space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell
      parameters a = b = 107.62, c = 120.76 A. X-ray diffraction data were collected to
      2.4 A resolution at 100 K using a synchrotron-radiation source.

PMID- 22139185
TI  - Expression, crystallization and preliminary crystallographic analysis of C
      reactive protein from zebrafish.
AB  - C-reactive protein (CRP) is an acute phase protein that is found in blood, the
      concentration of which in plasma rises rapidly in response to inflammation. It
      functions as a pattern-recognition molecule, recognizing dead cells and various
      pathogenic agents and eliminating them by utilizing the classical complement
      pathway and activating macrophages. CRP is phylogenetically highly conserved in
      invertebrates and mammals. To date, information on the CRP gene has been reported
      from numerous species of animals, but little is known about the structure of CRP
      from species other than humans. In order to solve the structure of CRP from bony
      fish, the CRP gene from zebrafiah (Danio rerio) was cloned and expressed in
      Escherichia coli. The zebrafish CRP (Dare-CRP) was then purified and
      crystallized. The crystal diffracted to 2.3 A resolution and belonged to space
      group R3, with unit-cell parameters a = b = 114.7, c = 61.0 A. The Matthews
      coefficient and solvent content were calculated to be 3.28 A(3) Da(-1) and
      62.55%, respectively. Determination of the zebrafish CRP structure should be
      helpful in investigating the evolution of CRPs in the innate immune system.

PMID- 22139186
TI  - Expression, purification and preliminary crystallographic analysis of Rv2247, the
      beta subunit of acyl-CoA carboxylase (ACCD6) from Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb) acyl-CoA carboxylase is involved in the
      biosynthesis of mycolic acids, which are a key component of the bacillus cell
      wall. The Mtb genome encodes six acyl-CoA carboxylase beta subunits (ACCD1-6),
      three of which (ACCD4-6) are essential for survival of the pathogen on minimal
      medium. Mtb ACCD6 has been expressed, purified and crystallized. The two forms of
      Mtb ACCD6 crystals belonged to space groups P4(1)2(1)2 and P2(1)2(1)2(1) and
      diffracted to 2.9 and 2.5 A resolution, respectively, at a synchrotron-radiation
      source.

PMID- 22139187
TI  - Purification, crystallization and preliminary crystallographic analysis of
      peroxidase from the palm tree Chamaerops excelsa.
AB  - Plant peroxidases are presently used extensively in a wide range of
      biotechnological applications owing to their high environmental and thermal
      stability. As part of efforts towards the discovery of appealing new
      biotechnological enzymes, the peroxidase from leaves of the palm tree Chamaerops
      excelsa (CEP) was extracted, purified and crystallized in its native form. An X
      ray diffraction data set was collected at a synchrotron source and data analysis
      showed that the CEP crystals belonged to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 70.2, b = 100.7, c = 132.3 A.

PMID- 22139188
TI  - Overexpression, purification, crystallization and preliminary X-ray analysis of
      CheY4 from Vibrio cholerae O395.
AB  - Chemotaxis and motility greatly influence the infectivity of Vibrio cholerae,
      although the role of chemotaxis genes in V. cholerae pathogenesis is poorly
      understood. In contrast to the single copy of CheY found in Escherichia coli and
      Salmonella typhimurium, four CheYs (CheY1-CheY4) are present in V. cholerae.
      While insertional disruption of the cheY4 gene results in decreased motility,
      insertional duplication of this gene increases motility and causes enhanced
      expression of the two major virulence genes. Additionally, cheY3/cheY4 influences
      the activation of the transcription factor NF-kappaB, which triggers the
      generation of acute inflammatory responses. V. cholerae CheY4 was cloned,
      overexpressed and purified by Ni-NTA affinity chromatography followed by gel
      filtration. Crystals of CheY4 grown in space group C2 diffracted to 1.67 A
      resolution, with unit-cell parameters a = 94.4, b = 31.9, c = 32.6 A, beta = 96.5
      degrees , whereas crystals grown in space group P3(2)21 diffracted to 1.9 A
      resolution, with unit-cell parameters a = b = 56.104, c = 72.283 A, gamma = 120
      degrees .

PMID- 22139189
TI  - Crystallization and preliminary X-ray crystallographic analysis of a helicase
      like domain from a tomato mosaic virus replication protein.
AB  - Tomato mosaic virus belongs to the genus Tobamovirus in the alphavirus-like
      superfamily of positive-strand RNA viruses. The alphavirus-like superfamily
      includes many plant and animal viruses of agronomical and clinical importance.
      These viruses encode replication-associated proteins that contain a putative
      superfamily 1 helicase domain. No three-dimensional structures for this domain
      have been determined to date. Here, the crystallization and preliminary X-ray
      diffraction analysis of the 130K helicase domain are reported. Diffraction data
      were collected and processed to 2.05 and 1.75 A resolution from native and
      selenomethionine-labelled crystals, respectively. The crystals belonged to the
      orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 85.8, b =
      128.3, c = 40.7 A.

PMID- 22139190
TI  - Crystallization of a 79 kDa fragment of the hook protein FlgE from Campylobacter
      jejuni.
AB  - A 79 kDa fragment of the bacterial flagellar hook protein FlgE from Campylobacter
      jejuni was cloned, overexpressed, purified and crystallized. Two different
      crystal forms were obtained. Synchrotron X-ray diffraction data showed that the
      first crystal form, which diffracted to 4.9 A resolution, belonged to the
      tetragonal crystal system, with space group I4(1)22 and unit-cell parameters a =
      b = 186.2, c = 386.6 A, alpha = beta = gamma = 90 degrees . The second crystal
      form diffracted to 2.5 A resolution and belonged to the monoclinic crystal
      system, with space group P2(1) and unit-cell parameters a = 75.7, b = 173.8, c =
      150.8 A, alpha = gamma = 90, beta = 106.5 degrees . SeMet protein was also
      overexpressed, purified and crystallized, and a 2.6 A resolution MAD data set was
      collected.

PMID- 22139191
TI  - Preliminary X-ray crystallographic studies on acetate kinase (AckA) from
      Salmonella typhimurium in two crystal forms.
AB  - Acetate kinase (AckA) catalyzes the reversible transfer of a phosphate group from
      acetyl phosphate to ADP, generating acetate and ATP, and plays a central role in
      carbon metabolism. In the present work, the gene corresponding to AckA from
      Salmonella typhimurium (StAckA) was cloned in the IPTG-inducible pRSET C vector,
      resulting in the attachment of a hexahistidine tag to the N-terminus of the
      expressed enzyme. The recombinant protein was overexpressed, purified and
      crystallized in two different crystal forms using the microbatch-under-oil
      method. Form I crystals diffracted to 2.70 A resolution when examined using X
      rays from a rotating-anode X-ray generator and belonged to the monoclinic space
      group C2, with unit-cell parameters a = 283.16, b = 62.17, c = 91.69 A, beta =
      93.57 degrees . Form II crystals, which diffracted to a higher resolution of 2.35
      A on the rotating-anode X-ray generator and to 1.90 A on beamline BM14 of the
      ESRF, Grenoble, also belonged to space group C2 but with smaller unit-cell
      parameters (a = 151.01, b = 78.50, c = 97.48 A, beta = 116.37 degrees ).
      Calculation of Matthews coefficients for the two crystal forms suggested the
      presence of four and two protomers of StAckA in the asymmetric units of forms I
      and II, respectively. Initial phases for the form I diffraction data were
      obtained by molecular replacement using the coordinates of Thermotoga maritima
      AckA (TmAckA) as the search model. The form II structure was phased using a
      monomer of form I as the phasing model. Inspection of the initial electron
      density maps suggests dramatic conformational differences between residues 230
      and 300 of the two crystal forms and warrants further investigation.

PMID- 22139196
TI  - Comment on: Markmiller M, Weiss T, Kreuz P, Ruter A, Konrad G. Partial
      weightbearing is not necessary after cementless total hip arthroplasty. Int
      Orthop. 2011 Aug;35(8):1139-43.

PMID- 22139192
TI  - In-house SAD phasing with surface-bound cerium ions.
AB  - The anomalous signal of cerium(III) ions present in a derivative of hen egg-white
      lysozyme (HEWL) crystals obtained by the addition of 0.025 M cerium chloride to
      the crystallization medium was used for phasing. X-ray intensity data were
      collected to 2 A resolution using an in-house Cu Kalpha radiation data-collection
      facility. Phasing of a single-wavelength data set purely based on its f'' led to
      a clearly interpretable electron-density map. Automated substructure solution by
      AutoSol in PHENIX resulted in four highest peaks corresponding to cerium(III)
      ions with data limited to 3 A resolution, and about 90% of the residues were
      built automatically by AutoBuild in PHENIX. Cerium(III) ions bound on the surface
      of the enzyme are found to interact mainly with the main-chain and side-chain
      carbonyl groups of Asn, Glu, Tyr and Asp and with water molecules. Ce(3+) ions
      were used as potential anomalous scatterers for the in-house single-wavelength
      anomalous scattering technique, and this is proposed as a tool for macromolecular
      phasing and for the study of the interactions of trivalent metal ions with
      proteins and other macromolecules.

PMID- 22139193
TI  - Seleno-detergent MAD phasing of leukotriene C4 synthase in complex with dodecyl
      beta-D-selenomaltoside.
AB  - Dodecyl-beta-D-selenomaltoside (SeDDM) is a seleno-detergent with a beta
      glycosidic seleno-ether in place of the ether moiety in dodecyl-beta-D-maltoside.
      Seleno-detergents are candidates for heavy-atom agents in experimental phasing of
      membrane proteins in protein crystallography. Crystals of a nuclear membrane
      embedded enzyme, leukotriene C(4) synthase (LTC(4)S), in complex with SeDDM were
      prepared and a multiwavelength anomalous diffraction (MAD) experiment was
      performed. The SeDDM in the LTC(4)S crystal exhibited sufficient anomalous
      diffraction for determination of the structure using MAD phasing.

PMID- 22139197
TI  - The outcome of the cementless tapered SL-Plus stem: an analysis of arthroplasty
      register data.
AB  - PURPOSE: The aim of this study is to evaluate the outcome of the cementless SL
      Plus stem in worldwide arthroplasty register datasets. METHODS: A structured
      analysis was conducted the registered data about the SL-Plus stem manufactured by
      Smith&Nephew including published data from Australia as well as previously
      unpublished datasets from the Registers of Lombardia, Italy and Valdoltra,
      Slovenia. A total of 75% of the data analysed had not been published so far. The
      primary outcome measure was the revision rate, calculated in revisions per 100
      observed component years. We evaluated a total of 10,684 primary and 122 revision
      surgeries with an average follow-up period of four years. RESULTS: All datasets
      showed good and reproducible results for treatment with the SL-Plus stem. An
      average of 0.31 revisions per 100 observed component years had been reported,
      which is considerably below the worldwide average (1.29) found for total hip
      arthroplasty independent of the product. The results of a large centre did not
      essentially deviate from the revision rates in Lombardia, where the numbers of
      cases per department are relatively low on average. CONCLUSIONS: There were no
      indications for product defects or relevant errors in application. The SL-Plus
      stem can be considered a high-quality product that ensures good results also in
      the hands of less experienced surgeons. Data from even young registers can
      substantially contribute to the assessment of implants, even with the short
      follow-up periods. These datasets particularly allow for valid assessment of
      safety issues and can therefore make an essential contribution to the solution of
      problems of current relevance.

PMID- 22139198
TI  - Antigen-presenting effects of effector memory Vgamma9Vdelta2 T cells in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs,
      but the pathogenic mechanism remains unclear. gammadelta T cells, a T-cell
      subpopulation, are characterized by multiple biological functions and associated
      with a variety of diseases. This study investigated the antigen-presenting
      effects of gammadelta T cells and their relationship with rheumatoid arthritis
      development. We found that Vgamma9Vdelta2 T cells (the predominant subtype of
      gammadelta T cells in peripheral blood) were activated by isopentenyl
      pyrophosphate to continuously proliferate and differentiate into effector memory
      cells. The effector memory Vgamma9Vdelta2 T cells exhibited phenotypic
      characteristics of specific antigen-presenting cells, including high HLA-DR and
      CD80/86 expression. These Vgamma9Vdelta2 T cells could present soluble antigens
      and synthetic peptides to CD4(+) T cells. Vgamma9Vdelta2 T cells with different
      phenotypes showed different cytokine secretion patterns. Effector memory
      Vgamma9Vdelta2 T cells simultaneously secreted not only interferon (IFN)-gamma
      but also IL-17. The peripheral blood and joint synovial fluid from RA patients
      contained numerous heterogeneous gammadelta T cells that were predominantly
      effector memory Vgamma9Vdelta2 T cells with the ability to secrete inflammatory
      factors. We also found that gammadelta T cells had a similar antigen-presenting
      capability to B cells. These results suggest that during the development of
      rheumatoid arthritis, gammadelta T cells can aggravate immune dysfunction and
      produce abnormal immune damage by secreting cytokines and inducing inflammatory
      cells to participate in synergistic inflammatory responses. Furthermore,
      gammadelta T cells can behave similarly to B cells to present viral peptides and
      autoantigen peptides to CD4(+) T cells, thus sustaining CD4(+) T-cell activation.

PMID- 22139199
TI  - Comparison of serotonin toxicity with concomitant use of either linezolid or
      comparators and serotonergic agents: an analysis of Phase III and IV randomized
      clinical trial data.
AB  - OBJECTIVES AND METHODS: The present study's objective was to evaluate serotonin
      toxicity with concomitant use of linezolid or comparators and serotonergic agents
      from 20 Phase III and IV comparator-controlled clinical studies on treatment of
      various Gram-positive infections. All reported adverse events were evaluated for
      serotonin toxicity using exact and surrogate terms consistent with Sternbach
      Criteria and Hunter Serotonin Toxicity Criteria. RESULTS: Baseline demographics
      and co-morbidities were similar between linezolid and comparator groups. No
      patients in either group were reported to have adverse events identified as
      serotonin toxicity. Among the patients receiving at least one serotonergic agent,
      9 of the 2208 (0.41%) linezolid patients and 3 of the 2057 (0.15%) comparator
      patients met the Sternbach Criteria [risk ratio (RR) 2.79; 95% confidence
      interval (95% CI) 0.76-10.31]; 3 (0.14%) of the linezolid patients and 1 (0.05%)
      of the comparator patients met the Hunter Serotonin Toxicity Criteria (RR 2.79;
      95% CI 0.29-26.85). No patients met both criteria. Most patients meeting criteria
      for serotonin toxicity had past or present co-morbidities that may have
      contributed to or overlapped with reported adverse events. CONCLUSIONS: While the
      potential exists for serotonin toxicity to occur with concomitant use of
      linezolid and serotonergic agents, the risk appears to be low. Based on the large
      database of Phase III and IV studies included in our analysis, we did not find
      enough evidence to conclude that linezolid-induced serotonin toxicity was
      different from that of comparators.

PMID- 22139200
TI  - [The other opinion: nephrotoxicity of low-dose methotrexate - a problem which
      does not exist].
AB  - The nephrotoxicity of methotrexate (MTX) is a phenomenon which is observed in
      high-dose therapy for treatment of malignant diseases. Even low-dose MTX therapy
      for treatment of rheumatic diseases is claimed to cause impairment in renal
      function. The necessity to adapt the dosage of MTX therapy for renal function
      disorders due to other causes however has first priority. The following article
      describes why nephrotoxicity of low-dose MTX has no clinical relevance and why in
      contrast non-steroidal anti-rheumatic drugs (NSARDs) are a problematic
      nephrotoxic group of substances and a long-term elimination from the therapeutic
      armamentarium for rheumatoid arthritis (RA) should be instigated.

PMID- 22139201
TI  - [Child and Adolescent Rheumatology].

PMID- 22139202
TI  - [Henoch-Schonlein purpura : most frequent form of vasculitis in childhood and
      adolescence].
AB  - Henoch-Schonlein purpura is the most common form of vasculitis in childhood and
      adolescence. It is manifested as palpable purpuras in the region of position
      dependent extremities with otherwise good clinical general condition. The
      expression on the skin can, however, be variable so that sometimes other
      differential diagnoses must be included. In typical cases an extensive diagnostic
      procedure is unnecessary but the short-term complications of abdominal symptoms
      as well as the long-term complications of nephritis should be pursued. If
      musculoskeletal symptoms occur paracetamol or non-steroidal anti-inflammatory
      drugs are effective as are steroids for reducing the duration of abdominal pain.
      The effectiveness of steroid prophylaxis of renal damage is still controversial.

PMID- 22139203
TI  - [Kawasaki disease in children and adolescents].
AB  - Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The
      diagnostic criteria are fulfilled with fever of unknown origin and 4 of the
      following 5 criteria: bilateral conjunctival injection, cervical lymphadenopathy,
      polymorphous rash, oral mucous membrane changes (injected lips, strawberry
      tongue) and peripheral extremity changes (erythema, edema, desquamation). If less
      than 4 criteria are found incomplete KD can be diagnosed. The therapy is 2 g/kg
      body weight single dose intravenous immunoglobulin and acetylsalicylic acid
      (ASS). In the long-term follow-up the main focus is on the coronary arteries
      because coronary changes play a key role in the intensity of long-term
      management. There is some evidence that KD is a risk factor for cardiovascular
      diseases in adults.

PMID- 22139204
TI  - [Tuberculosis : diagnostics and prophylaxis].
AB  - Infection with Mycobacterium tuberculosis causes primarily formation of
      granulomatous tubercles in the lungs. In the absence of any clinical symptoms it
      is named latent tuberculosis infection which can be an origin of reactivation,
      especially as a consequence of an impaired response of the immune system.
      Complete anamnesis, radiographic methods and bacteriological analysis
      (microscopy, culture, PCR) are useful for diagnosis of tuberculosis. Since 2005
      newer in vitro tests are available using interferon-gamma release assays (IGRAs).
      Compared to the tuberculin skin test it is possible to differentiate between
      infection with M. tuberculosis and individuals vaccinated with the Bacillus
      Calmette-Guerin (BCG) vaccine. These new in vitro tests are part of a screening
      procedure which has to be performed before starting immunosuppressive therapy
      with tumor necrosis factor-alpha (TNF-alpha) inhibitors. In cases of latent
      tuberculosis infection administration of isoniazid for 9 months is recommended.

PMID- 22139205
TI  - [Th1, Th17 and Th1+17 cells].
AB  - T helper cells contribute to the induction and maintenance of rheumatic
      inflammation through the secretion of cytokines. The analysis of Th1 cells
      expressing interferon-gamma, Th17 cells expressing interleukin-17 and the newly
      described Th1+17 cells could give insight into the pathophysiological mechanisms
      of rheumatic diseases. This could lead to the development of novel, targeted
      therapeutic strategies.

PMID- 22139211
TI  - Huge Casimir effect at finite temperature in electromagnetic Rindler space.
AB  - We investigate the Casimir effect at a finite temperature in the electromagnetic
      Rindler space, and we find that the Casimir energy is proportional to T(4)/d(2)
      in the high-temperature limit, where T ~ 27  degrees C is the temperature and d ~
      100 nm is a small cutoff. We propose to make metamaterials to mimic the Rindler
      space and measure the predicted Casimir effect. Because the parameters of
      metamaterials we proposed are quite simple, this experiment would be easily
      implemented in the laboratory.

PMID- 22139207
TI  - [Statement of the German Society of Rheumatology (DGRh) reporting on the
      Institute's plan for biologicals in the second-line therapy for rheumatoid
      arthritis].

PMID- 22139206
TI  - [Insufficiency fractures of the feet and lower limbs in rheumatoid arthritis].
AB  - BACKGROUND: Insufficiency fractures are generally a rare event, especially of the
      hindfoot. These are often overlooked in the initial stage, however, they must be
      regarded as a differential diagnosis in the range of possible causes in patients
      with rheumatoid arthritis and unclear complaints. MATERIAL AND METHODS:
      Outpatients in an arthritis care unit from 2009-2011 were analyzed for fractures
      of the hindfoot and distal tibia. RESULTS: A total of six patients with seven
      fractures without adequate trauma were found in the cohort. All patients had
      received disease modifying therapy and corticosteroids. All fractures could be
      successfully treated without surgery. CONCLUSION: Insufficiency fractures in
      patients with rheumatoid arthritis are a typical finding after several years of
      the disease. They are directly related to the disease and medication and can
      usually be successfully treated conservatively.

PMID- 22139212
TI  - Efficient red-emitting phosphor for near-ultraviolet-based solid-state lighting.
AB  - Eu(3+) ion activated Y(2)MoO(6) synthesized by the sol-gel method had been
      investigated as an alternative red-emitting phosphor for solid-state lighting.
      Excitation spectra, emission spectra, and decay curves were measured to
      characterize the luminescent properties. The phosphor shows efficient absorption
      of near-ultraviolet (NUV) light, and it also exhibits excellent performance in
      emission intensity and color purity compared with the commercial phosphor in
      current use. This red-emitting material may be applied as a promising red
      component for the NUV excited white diode.

PMID- 22139213
TI  - Coherent single-cycle pulses with MV/cm field strengths from a relativistic
      transition radiation light source.
AB  - Terahertz (THz) pulses with energies up to 100 MUJ and corresponding electric
      fields up to 1 MV/cm were generated by coherent transition radiation from 500 MeV
      electron bunches at the free-electron laser Freie-Elektronen-Laser in Hamburg
      (FLASH). The pulses were characterized in the time domain by electro-optical
      sampling by a synchronized femtosecond laser with jitter of less than 100 fs.
      High THz field strengths and quality of synchronization with an optical laser
      will enable observation of nonlinear THz phenomena.

PMID- 22139214
TI  - Excitability in a semiconductor laser with saturable absorber.
AB  - We show that a monolithic and compact vertical cavity laser with intracavity
      saturable absorber can emit short excitable pulses. These calibrated optical
      pulses can be excited as a response to an input perturbation whose amplitude is
      above a certain threshold. Subnanosecond excitable response is promising for
      applications to novel all-optical devices for information processing or logical
      gates.

PMID- 22139215
TI  - Optical cloaking of cylindrical objects by using covers made of core-shell
      nanoparticles.
AB  - In this Letter, we propose an engineered design of optical cloaks based on the
      scattering cancellation technique and intended to reduce the observability of
      cylindrical objects. The cover, consisting of a periodic arrangement of core
      shell nanospheres, is designed in such a way to exhibit near-zero values of the
      real part of the homogenized effective permittivity at optical frequencies. Full
      wave numerical simulations, considering the measured data of the dielectric
      function of the plasmonic material composing the shell, show that the cloak is
      able to reduce by about 6 dB the scattering cross section of a finite-length
      cylinder at around 740 THz with a -3 dB fractional bandwidth of about 7%. We show
      also that this result is not significantly affected by the perturbation of the
      periodic alignment of the core-shell nanospheres, due to possible fabrication
      issues or to an amorphous arrangement.

PMID- 22139216
TI  - Single S-tapered fiber Mach-Zehnder interferometers.
AB  - A fiber Mach-Zehnder interferometer (MZI) sensor, novel to our knowledge, based
      on a single "S"-like fiber taper has been fabricated via applying nonaxial pull
      in fiber tapering by a fusion splicer. The typical feature size of the structure
      has a length of 660 MUm and the axial offset of 96 MUm. This S fiber taper MZI
      has a refractive index (RI) sensitivity of 1590 nm/refractive index unit in the
      RI range of 1.409-1.425 and a strain sensitivity of about -60 pm/microstrain,
      which is 30 times higher than that of the normal two-taper-based MZI sensors.

PMID- 22139217
TI  - Highly efficient Tm:YAG ceramic laser resonantly pumped at 1617 nm.
AB  - We report on a highly efficient polycrystalline Tm:YAG ceramic laser in-band
      pumped by an Er:YAG laser at 1617 nm. Lasing characteristics of 4.0 and 6.0
      at.%Tm(3+)-doped YAG ceramics were investigated and compared. With an output
      coupler of 10% transmission, a maximum output power of 7.3 W was obtained at 2015
      nm under 12.8 W of incident pump power, corresponding to a slope efficiency with
      respect to incident pump power of 62.3%.

PMID- 22139218
TI  - Wavelength division (de)multiplexing based on dispersive self-imaging.
AB  - We proposed and experimentally demonstrated wavelength division (de)multiplexers
      (WDMs) utilizing the wavelength dispersive nature of self-imaging multimode
      interferometers. Proof-of-principle devices fabricated on the silicon-on
      insulator platform operated as 4-channel WDMs with a free spectral range of >90
      nm, an averaging cross talk of <-20 dB for a 1 nm band, and an insertion loss of
      <2.0 dB. The potential for higher channel counts and smaller channel wavelength
      spacing was also predicted. This type of WDM is easy to design and fabricate. The
      underlying concept is applicable to all planar waveguide platforms.

PMID- 22139219
TI  - Bending insensitivity of fiber Bragg gratings in suspended-core optical fibers.
AB  - This Letter presents simulation and experimental results that explore bending
      insensitivity of fiber Bragg gratings in suspended-core optical fibers. The
      implementation of thin silica bridge in the fibers enhances index contrast of the
      fiber core and reduces bending-induced strain transfer to the fiber core. This
      fiber design lead to a reduction of over 7 times in strain-induced fiber Bragg
      grating resonant peak shifts in the suspended-core fiber compared with that in
      standard telecommunication fiber, and an 0.14 dB bending loss at a bending radius
      of 6.35 mm.

PMID- 22139220
TI  - Dual-band optical filter based on a single microdisk resonator.
AB  - We propose and experimentally demonstrate a dual-band optical filter based on a
      single microdisk resonator. An analytical model is built based on the transfer
      matrix method and is applied to simulate the properties of such a device.
      Competition and interference of the dual modes in the resonator lead to dual-band
      filtering with high isolation. As the finite-difference time-domain simulation
      illustrates, two low-order resonant modes can be effectively triggered by
      optimizing the waveguide width and spacing gap between the compact resonator and
      waveguides. In experiment, a double side-coupled microdisk resonator was
      fabricated on a nanophotonic silicon-on-insulator platform, and dual-band
      bandpass filtering is realized with an optical isolation higher than 20 dB and an
      insertion loss lower than 2 dB. The experimental results agree well with our
      modeling results.

PMID- 22139221
TI  - Beyond-limit light focusing in the intermediate zone.
AB  - We experimentally verify that a new nanolens of a designed plasmonic aperture can
      focus visible light to a single line with its width smaller than the limit of
      half the wavelength in the intermediate zone. The experimental measurement
      indicates that while the near field plays a role to increase the spot size in the
      near zone, it is negligible at the beyond-limit focused region; i.e., the focused
      light is dominated by the radiative fields. The image taken by the optical
      microscope shows that the fields focused have propagated to the far zone. Besides
      being of academic interest, the nanolens capable in achieving a lower diffraction
      limit in the intermediate zone is important for application possibilities.

PMID- 22139222
TI  - Method for the determination of dopant concentrations of luminescent ions.
AB  - We report on a new method for determining dopant ion concentrations in laser
      materials. This method is based on optical absorption spectroscopy. In contrast
      to other methods used to measure the dopant concentration that are based on
      absorption measurements, this method does not require the knowledge of the
      absorption cross sections. An advantage of this method compared to the micro
      probe analysis is that only concentrations of dopant ions of a certain valency,
      which are luminescent, are detected. The method is sensitive especially for small
      doping concentrations of ions with high absorption cross sections. Another
      application of this method is the determination of the ratio between luminescent
      dopant ions to the total number of dopant ions in the case that not all dopant
      ions are on crystal sites that allow for optical transitions.

PMID- 22139223
TI  - Analysis of broad emission direction in a spiral-shaped microcavity laser.
AB  - Broad emission direction with two lobes is analyzed in a spiral-shaped
      microcavity laser. By pumping the boundary of the InGaAsP semiconductor laser
      with dc current injection, whispering-gallery-type modes emitting through a notch
      are obtained. By classifying the lasing modes into mode groups based on the
      equidistant mode spacing, it is shown that each mode group has its own emission
      direction with a narrow divergence angle and that a superposition of emission
      direction of dominant mode groups reproduces a far-field pattern of total
      intensity with two lobes, which is contrary to theoretical results.

PMID- 22139224
TI  - Optical Mobius strips, twisted ribbons, and the index theorem.
AB  - The twist numbers of circular optical Mobius strips and twisted ribbons are shown
      to obey the index theorem under rotation of the plane of observation, and under
      change in the radius of the path.

PMID- 22139225
TI  - Test of the all-optical control of wave-particle duality of cavity photons by
      ordinary photodetection.
AB  - The principle of complementarity refers to the ability of quantum entities to
      behave as particles or waves under different experimental conditions. We present
      a proposal for the experimental observation of the ultrafast all-optical control
      of the wave-particle duality of light. The device is constituted by a three-level
      quantum emitter strongly coupled to a microcavity (MC) and can be realized by
      exploiting a great variety of systems, ranging from atomic physics and
      semiconductor quantum dots to intersubband polaritons and Cooper pair boxes. The
      wavelike or particlelike behavior of MC photons can be probed by simply measuring
      the cavity output photon rate after excitation with pairs of phase-locked weak
      pulses with precise arrival times.

PMID- 22139226
TI  - Stereophotogrammetric 3D shape measurement by holographic methods using
      structured speckle illumination combined with interferometry.
AB  - We present a unique combination of the numerical three-dimensional (3D)
      reconstruction of the shape of an object with interferometric deformation
      measurements. Two cameras record several holograms of an object that is
      illuminated by structured illumination. This illumination is realized by speckle
      patterns. To improve the image quality, an inplace speckle reduction technique is
      combined with the structured illumination to reduce the effect of disturbing
      subjective speckles which appear in the reconstructed images.
      Stereophotogrammetric methods are applied to extract the 3D surface information
      of the object out of the reconstructed images. Since the recording is done by
      holography and because stereophotogrammetry enables a pointwise correlation
      between the two views, it is possible to combine other holographic techniques
      with the reconstructed 3D shape. This is demonstrated by an interferometric
      deformation measurement of an object cooling down. The resulting interferometric
      fringes are mapped onto the reconstructed 3D surface. Hence, the proposed method
      enables automatic and dense matching of interferometric fringe-maps recorded by
      spatially separated holograms onto the surface of the object, which has not yet
      been realized by existing techniques.

PMID- 22139227
TI  - Reconstruction for limited-projection fluorescence molecular tomography based on
      projected restarted conjugate gradient normal residual.
AB  - Limited-projection fluorescence molecular tomography (FMT) can greatly reduce the
      acquisition time, which is suitable for resolving fast biology processes in vivo
      but suffers from severe ill-posedness because of the reconstruction using only
      limited projections. To overcome the severe ill-posedness, we report a
      reconstruction method based on the projected restarted conjugate gradient normal
      residual. The reconstruction results of two phantom experiments demonstrate that
      the proposed method is feasible for limited-projection FMT.

PMID- 22139228
TI  - Three-dimensional profilometry with nearly focused binary phase-shifting
      algorithms.
AB  - This Letter investigates the effects of different phase-shifting algorithms on
      the quality of high-resolution three-dimensional (3-D) profilometry produced with
      nearly focused binary patterns. From theoretical analyses, simulations, and
      experiments, we found that the nine-step phase-shifting algorithm produces
      accurate 3-D measurements at high speed without the limited depth range and
      calibration difficulties that typically plague binary defocusing methods. We also
      found that the use of more fringe patterns does not necessarily enhance
      measurement quality.

PMID- 22139229
TI  - Efficient laser emissions at 1.06 MUm of swift heavy ion irradiated Nd:YCOB
      waveguides.
AB  - We report on the fabrication of Nd:YCOB (Nd:YCa(4)O(BO(3))(3)) optical waveguides
      by using 170 MeVAr(8+) ion irradiation at an ultralow fluence of 2*10(12)
      ions/cm(2). The confocal microphotoluminescence investigation on the produced
      waveguides has shown the well-preserved fluorescence features within the guiding
      layer with respect to the bulks. Under the optical pump at wavelength of 810 nm,
      continuous wave waveguide lasers at 1061.2 nm have been generated at room
      temperature with a high slope efficiency of ~67.9%.

PMID- 22139231
TI  - Optical-RF frequency stability transformer.
AB  - An optical technique based on stability transfer among modes of a monolithic
      optical microresonator is proposed for long term frequency stabilization of a
      radio frequency (RF) oscillator. We show that locking the frequency difference of
      two microresonator modes with dissimilar sensitivity to an applied forcing
      function to a master RF oscillator improves the long term stability of a slave RF
      oscillator locked to the frequency difference of another pair of modes with
      nearly identical sensitivity to the same forcing function. For instance, the
      stability of a 10 MHz master oscillator with Allan deviation of 10(-7) at 10(3) s
      can be improved and transferred to a slave oscillator with identical free running
      stability performance, so that the resultant Allan deviation of the slave
      oscillator becomes equal to 10(-13) at 10(3) s. The suggested method does not
      require absolute frequency references.

PMID- 22139230
TI  - Mode field diameter preserving fiber tapers.
AB  - An approach for preserving the mode field diameter (MFD) in fiber tapers is
      demonstrated. The approach utilizes concentric dual-core fibers, which couple
      light from an inner core to an outer core through a taper. Fibers with a 6 MUm
      MFD feedthrough and a 15 MUm polarization maintaining feedthrough are
      demonstrated experimentally. Simulations of the MFD in the tapered dual-core
      fibers are also presented.

PMID- 22139232
TI  - Optical storage with electromagnetically induced transparency in a dense cold
      atomic ensemble.
AB  - We experimentally investigate optical storage with electromagnetically induced
      transparency in a dense cold (85)Rb atomic ensemble. By varying the optical depth
      (OD) from 0 to 140, we observe that the optimal storage efficiency has a
      saturation value of 50% as OD>50. Our result is consistent with that obtained
      from hot vapor cell experiments.

PMID- 22139233
TI  - Circularly polarized unidirectional emission via a coupled plasmonic spiral
      antenna.
AB  - In this Letter, we study the emission properties of an electric dipole emitter
      coupled to a plasmonic spiral structure. The plasmonic spiral structure functions
      as an optical antenna, coupling the electric dipole emission into circularly
      polarized unidirectional emission in the far field. Increasing number of turns of
      the spiral leads to narrower angular width of the emission pattern in the far
      field. For a spiral antenna with six turns, antenna directivity of 23.5 dB with a
      directional emission into a narrow angular cone of 4.3 degrees  can be achieved.
      The emitted photons carry spin that is essentially determined by the handedness
      of the spiral antenna. By reversing the spiral, one can switch the polarization
      of the emission field between left-hand and right-hand circular polarizations.
      The spiral antenna may be used as a nanoscale circular polarization source in
      single molecule sensing, single-photo sources, and integrated photonic circuits.

PMID- 22139234
TI  - Tuning whispering gallery modes using internal aerostatic pressure.
AB  - Aerostatic tuning of whispering gallery modes (WGMs) in a microbubble resonator
      is demonstrated. The optical modes are redshifted over hundreds of gigahertz
      (GHz) simply by increasing the air pressure (up to 6 bars) inside the
      microbubble. A description of the pressure tuning properties of the WGMs in
      microbubbles is given in terms of the corresponding elasto-optical equations of
      spherical shells and the results are compared to experimental data. Microbubbles
      as small as 74 MUm are tested and the experimental results show excellent
      agreement with the theory. An estimation method is developed for calculating the
      wall thicknesses of the microbubbles from the diameters, which are measured via
      direct microscopy. A geometrical factor chi is defined and a linear relationship
      between the shift rate (GHz/bar) of the bubbles modes and chi is observed.

PMID- 22139235
TI  - Diffraction-free propagation of a focused delta-pulsed beam.
AB  - The propagation of short broadband pulses in a homogeneous medium is analyzed on
      the basis of the wave equation and in the parabolic approximation of that
      equation. It is shown that the diffraction spreading of a focused optical pulsed
      beam does not occur in the limiting case of a delta pulse.

PMID- 22139236
TI  - Picosecond flat-top pulse generation using dual-mode fiber Mach-Zehnder
      interferometers.
AB  - We report on an optical fiber Mach-Zehnder interferometer made by offset splicing
      a dual-mode fiber with two single-mode fibers. The extinction ratio can be tuned
      from less than 1 dB to greater than 28 dB by rotating the dual-mode fiber along
      its axial direction. The interferometer is utilized as a pulse shaper to convert
      a 2.5 ps Gaussian pulse to a 5.2 ps flat-top pulse.

PMID- 22139237
TI  - Optical fiber-based photomechanical gene transfer system for in vivo application.
AB  - We developed an optical-fiber-based photomechanical gene transfer system for
      endoscopic or catheter-based application. A fiber tip with a laser-absorbing film
      covered with a transparent plastic disk for plasma confinement was attached to a
      quartz fiber; the film was irradiated with nanosecond laser pulses transmitted
      through the fiber to generate photomechanical waves (PMWs). Characteristics of
      PMWs emitted from the fiber tip were examined to confirm the necessary conditions
      for gene transfer. We then attempted to transfer reporter genes to the rat skin
      as a test tissue in vivo with the fiber system, and the results showed
      significantly high protein levels and spatially selective pinpoint gene
      expressions in the tissue.

PMID- 22139238
TI  - Strain field manipulation in ultrafast laser inscribed BiB3O6 optical waveguides
      for nonlinear applications.
AB  - A novel technique was used to control the spatial overlap of the orthogonal
      linearly polarized waveguide modes in ultrafast laser inscribed BiB(3)O(6)
      waveguides. We report that the strain fields induced by the expansion of material
      in the laser focus can be considered independently in the design of "type II"
      waveguides guiding orthogonal linearly polarized light. The waveguide with the
      optimal mode overlap was used for type I birefringently phase-matched second
      harmonic generation of a continuous wave laser source at 1047 nm.

PMID- 22139239
TI  - Near-infrared ultrabroadband luminescence spectra properties of subvalent bismuth
      in CsI halide crystals.
AB  - We observed two ultrabroadband near-infrared (NIR) luminescence bands around 1.2
      and 1.5 MUm in as-grown bismuth-doped CsI halide crystals, without additional
      aftertreatment. Dependence of the NIR emission properties on the excitation
      wavelength and measurement temperature was studied. Two kinds of NIR active
      centers of subvalent bismuth and color centers were demonstrated to coexist in
      Bi:CsI crystal. The eye-safe 1.5 MUm emission band with an FWHM of 140 nm and
      lifetime of 213 MUs at room temperature makes Bi:CsI crystal promising in the
      applications of the ultrafast laser and ultrabroadband amplifier.

PMID- 22139240
TI  - Equivalence of structure constants in non-Kolmogorov and Kolmogorov spectra.
AB  - We find the equivalence of the structure constants in non-Kolmogorov and
      Kolmogorov spectra in a turbulent atmosphere. As the reference point, the
      spherical wave scintillation index in a non-Kolmogorov medium is used. Relations
      of the structure constants are found to be functions of the power law of the
      turbulence spectrum and the Fresnel zone. It will be useful to employ the
      equivalence of the structure constants in making performance comparisons found
      with non-Kolmogorov and Kolmogorov spectra.

PMID- 22139241
TI  - Avoiding bandwidth collapse in long chains of coupled optical microresonators.
AB  - Coupled photonic oscillators and resonators are sensitive to unavoidable
      nanoscale disorder, and localization in periodic structures induced by disorder
      leads eventually to a complete collapse of the bandwidth, which is generally
      considered problematic for device applications. Here, we investigate the
      dependence of bandwidth collapse on the interresonator coupling coefficient, a
      parameter controllable by lithography or device operation.

PMID- 22139243
TI  - Optical filter with tunable wavelength and bandwidth based on cholesteric liquid
      crystals.
AB  - An optical filter with tunable wavelength and bandwidth has been demonstrated
      using two cholesteric liquid crystals configured in a reflection mode, in which
      the incident light is first reflected by one cholesteric liquid crystal and then
      by the other one. The central wavelength can be tuned from 527 nm to 574 nm and
      the bandwidth can be changed from 10 nm to 80 nm. It has potential applications
      in many fields, especially in optical communications and multispectral and
      hyperspectral imaging systems.

PMID- 22139244
TI  - Zeno effect and switching of solitons in nonlinear couplers.
AB  - The Zeno effect is investigated for soliton type pulses in a nonlinear
      directional coupler with dissipation. The effect consists in increase of the
      coupler transparency with increase of the dissipative losses in one of the arms.
      It is shown that localized dissipation can lead to switching of solitons between
      the arms. Power losses accompanying the switching can be fully compensated by
      using a combination of dissipative and active (in particular, parity-time
      symmetric) segments.

PMID- 22139242
TI  - Frequency-domain photoacoustic phased array probe for biomedical imaging
      applications.
AB  - We report the development of a frequency-domain biomedical photoacoustic imaging
      system that utilizes a continuous-wave laser source with a custom intensity
      modulation pattern, ultrasonic phased array for signal detection, and processing
      coupled with a beam-forming algorithm for reconstruction of photoacoustic
      correlation images. Sensitivity to optical contrast was demonstrated using tissue
      mimicking phantoms and in-vivo tissue samples.

PMID- 22139245
TI  - Full-band quantum-dynamical theory of saturation and four-wave mixing in
      graphene.
AB  - The linear and nonlinear optical response of graphene are studied within a
      quantum-mechanical, full-band, steady-state density-matrix model. This
      nonpurtabative method predicts the saturatable absorption and saturable four-wave
      mixing of graphene. The model includes tau(1) and tau(2) time constants that
      denote carrier relaxation and quantum decoherence, respectively. Fits to existing
      experimental data yield tau(2) < 1 fs due to carrier-carrier scattering. tau(1)
      is found to be on the timescale from 250 fs to 550 fs, showing agreement with
      experimental data obtained by differential transmission measurements.

PMID- 22139246
TI  - High-speed modal decomposition of mode instabilities in high-power fiber lasers.
AB  - A high-speed mode analysis technique is required to gain fundamental
      understanding of mode instabilities in high-power fiber laser systems. In this
      work a technique, purely based on the intensity profile of the beam, is
      demonstrated to be ideally suited to analyze fiber laser dynamics. This
      technique, together with a high-speed camera, has been applied to the study of
      the temporal dynamics of mode instabilities at high average powers with up to
      20,000 frames per second. These measurements confirm that energy transfer between
      the fluctuating transversal modes takes place in millisecond-time-scale.

PMID- 22139247
TI  - In vivo imaging of intrinsic optical signals in chicken retina with functional
      optical coherence tomography.
AB  - Visually evoked intrinsic optical signals (IOSs) were measured in vivo for the
      first time to our knowledge from all retina layers of the chicken retina with a
      combined functional optical coherence tomography and electroretinography (ERG)
      system. IOS traces were recorded from a small volume in the retina with 3.5 MUm
      axial resolution and 7 ms time resolution. Comparison of the IOS and ERG traces
      shows a correlation between the positive and negative IOS measured from different
      retinal layers and the timing of the a and b waves in the ERG recording.

PMID- 22139248
TI  - Signal beating elimination using single-mode fiber to multimode fiber coupling.
AB  - We experimentally demonstrate an all-passive fiber-based approach to prevent
      undesired beating during signal merging and detection. Beating occurs when
      optical signals of very close or the same wavelength are combined at a coupler
      and detected using a photodetector. Our approach is based on signal coupling from
      several single-mode fibers to a single piece of multimode fiber without
      interference, such that different signals propagate in different modes with
      different spatial positions inside the multimode fiber. We have investigated
      signal beating when the signals are coherent, partially coherent, or incoherent
      with each other. The measured results for single-mode to multimode coupling show
      signal beating is substantially reduced, resulting in widely opened eye diagrams
      and error-free bit error rate performance.

PMID- 22139249
TI  - Femtosecond high-power spontaneous mode-locked operation in vertical-external
      cavity surface-emitting laser with gigahertz oscillation.
AB  - We realize a femtosecond high-power spontaneous mode-locked operation with
      gigahertz oscillation in a vertical-external cavity surface-emitting laser under
      the condition of eliminating the internal and external unwanted reflection. We
      find that the reflectivity of the output coupler has a significant influence not
      only on the output power but also on the output pulse duration. With an incident
      pump power of 20 W, we have achieved 2.35 W of average output power with 778 fs
      pulse duration at a repetition rate of 2.17 GHz. The shortest pulse duration was
      654 fs at an average output power of 0.45 W.

PMID- 22139250
TI  - Plasmonic critical angle in optical transmission through subwavelength metallic
      gratings.
AB  - We observe and theoretically analyze the plasmonic analog of the critical angle
      phenomenon in optical transmission through subwavelength gratings milled in an
      optically thick metal film. The total transmission from a denser medium to a less
      dense one vanishes while the total reflection holds very strong, providing the
      incidence angle increases past the plasmonic critical angle (PCA). The conditions
      and physical origins of the total internal reflection above the PCA are
      clarified.

PMID- 22139252
TI  - Polarimetric target detection in the presence of spatially fluctuating Mueller
      matrices.
AB  - In polarimetric imaging systems, the main source of perturbations may not be
      detection noise but fluctuations of the Mueller matrices in the scene. In this
      case, we propose a method for determining the illumination and analysis
      polarization states that allow reaching the highest target detection performance.
      We show with simulations and real-world images that, in practical applications,
      the statistics of Mueller matrix fluctuations have to be taken into account to
      optimize polarimetric imagery.

PMID- 22139251
TI  - Self-trapping and splitting of bright vector solitons under inhomogeneous
      defocusing nonlinearities.
AB  - We show that bimodal systems with a spatially nonuniform defocusing cubic
      nonlinearity, whose strength grows toward the periphery, can support stable two
      component solitons. For a sufficiently strong cross-phase-modulation interaction,
      vector solitons with overlapping components become unstable, while stable
      families of solitons with spatially separated components emerge. Stable complexes
      with separated components may be built not only of fundamental solitons, but of
      multipoles, too.

PMID- 22139253
TI  - Nondegenerate four-wave-mixing-based radio frequency up/downconversion using a
      parametric loop mirror.
AB  - We propose a method of reconfigurable radio frequency up/downconversion using a
      parametric optical loop mirror. The baseband optical signal can be unconverted to
      a carrier-suppressed radio-over-fiber signal at a wide range of frequencies
      without the help of optical filters to remove the optical carrier. Upconversion
      of up to 60 GHz and downconversion from 40 GHz for both single-channel and
      wavelength-division-multiplexing signals using the same setup are demonstrated.

PMID- 22139255
TI  - Design of transverse electric ring isolators for ultra-low-loss Si3N4 waveguides
      based on the finite element method.
AB  - In this Letter we present the design of a novel (to our best knowledge)
      integrated TE isolator realized using ultra-low-loss Si(3)N(4) waveguides. The
      device is made of two straight waveguides coupled to an array of ring resonators
      including a Ce:YIG garnet grown on their internal side. The analysis demonstrates
      advantages in loss, isolation, and passband width as the number of rings is
      increased.

PMID- 22139254
TI  - Incoherent optical processor for nondirectional edge enhancement of color images.
AB  - We present an optical method for nondirectional edge extraction/enhancement in
      color images. The method is based on the capability of twisted-nematic LCDs to
      traduce the image information in changes of the state of polarization of light,
      which allows us to generate simultaneously two replicas of the digital image
      displayed on the LCD: a true-color ("positive") image and a complementary-color
      ("negative") one. In our setup the imaging system consists of a lens plus a pupil
      mask formed with concentric apertures and orthogonal polarizers. This layout
      allows us to simultaneously image a well-focused positive replica (due to the
      circular aperture) superimposed to a slightly defocused negative one (due to the
      annular aperture). It is not difficult to demonstrate that this generates a
      nondirectional (Laplacian) edge enhancement. Unlike Fourier, our proposal works
      with incoherent illumination and does not require precise alignment, and thus, it
      could be a useful tool for edge extraction/enhancement in large images in real
      time applications. Validation experiments are presented.

PMID- 22139256
TI  - I/Q intensity-demodulation analog photonic link based on polarization modulator.
AB  - We experimentally investigate a high-linearity analog photonic link based on
      polarization-modulation in-phase/quadrature (I/Q) intensity-demodulation. In the
      proposed system, a light wave with its polarization direction oriented at an
      angle of 45 degrees  with respect to the principal axis of the polarization
      modulator (PolM) is polarization modulated by a drive signal. In the receiver,
      the polarization-modulated signal is split into two paths using a 50:50 optical
      coupler (OC). In each path, a polarization beam splitter (PBS) is connected to
      the PolM via a polarization controller (PC) to realize the in-phase and
      quadrature signal, respectively. Thanks to the polarization-modulation to
      intensity-modulation conversion, the fluctuation of the optical phase noise has
      no impact on the coherent signals. In addition, the use of a single PolM allows
      the link avoids the matching requirements of dual modulator schemes. The
      linearization leads to suppression of the third-order intermodulation (IMD3) by
      more than 40 dB, compared to the quadrature signal. Experimental results show
      that the link gain is -11.5 dB, noise figure is 26.5 dB, and the third-order
      limited spurious free dynamic range (SFDR) is 124 dB in a 1 Hz bandwidth.

PMID- 22139257
TI  - 1 MHz repetition rate hollow fiber pulse compression to sub-100-fs duration at
      100 W average power.
AB  - We report on nonlinear pulse compression at very high average power. A high-power
      fiber chirped pulse amplification system based on a novel large pitch photonic
      crystal fiber delivers 700 fs pulses with 200 MUJ pulse energy at a 1 MHz
      repetition rate, resulting in 200 W of average power. Subsequent spectral
      broadening in a xenon-filled hollow-core fiber and pulse compression with chirped
      mirrors is employed for pulse shortening and peak power enhancement. For the
      first time, to our knowledge, more than 100 W of average power are transmitted
      through a noble-gas-filled hollow fiber. After pulse compression of 81 fs, 93 MUJ
      pulses are obtained at a 1 MHz repetition rate.

PMID- 22139258
TI  - Adaptive aberration correction of GRIN lenses for confocal endomicroscopy.
AB  - Graded-index (GRIN) lenses serve as a key component for miniature endoscopes
      because of their small diameters and ease of assembly. However, the nonaplanatic
      nature of GRIN lenses causes inherent spatial aberrations that lower image
      resolution and sharpness. Here we present the diagnosis of the aberrations in
      GRIN probes and the use of adaptive optics to compensate for the wavefront errors
      in the endoscope. Two different operation schemes based on preset and in situ
      measurements are demonstrated, both resulting in a substantial reduction of the
      wavefront error from 0.42 to <0.1 MUm.

PMID- 22139259
TI  - Electrodeless-discharge-vapor-lamp-based Faraday anomalous-dispersion optical
      filter.
AB  - We report an excited-state Faraday anomalous-dispersion optical filter operating
      on the rubidium 5P(3/2)-5D(5/2) transition (775.9 nm in vacuum) without the use
      of a pump laser. An electrodeless discharge vapor lamp is employed to replace the
      Rb vapor cell in a traditional Faraday anomalous-dispersion optical filter
      system. Atoms can be excited by power rather than a complex frequency-locked pump
      laser. A proof-of-concept experimental demonstration with a maximum transmission
      of 1.9% and a filter bandwidth of 650 MHz is presented.

PMID- 22139260
TI  - Extended depth of field by colored apodization.
AB  - We describe an approach to achieving extended depth of field for a camera system
      based on reducing the aperture of the blue channel of a three-color camera by
      apodizing the lens with a yellow-colored filter. The resulting improvement in
      depth of field for the blue channel allows red and green channels to be digitally
      postprocessed for improved sharpness. Simulation confirms that our approach
      renders the modular transfer function of the system less dependent on object
      depth. Experimental test images verify the improvement in depth of field.

PMID- 22139261
TI  - Phase extraction in speckle interferometry by a circle fitting procedure in the
      complex plane.
AB  - In speckle interferometry (SI), temporal signals are amplitude- and frequency
      modulated signals and exhibit a fluctuating background. Prior to phase
      computation, this background intensity must be eliminated. Here our approach is
      to build a complex signal from the raw one and to fit a circle through the points
      cloud representing its sampled values in the complex plane. The circle fit is
      computed from a set of points whose length is locally adapted to the signal. This
      procedure-new to our knowledge in SI-yields the background and the modulation
      depth and leads to the determination of the instantaneous frequency. The method,
      applied to simulated and experimental signals, is compared to empirical mode
      decomposition (EMD). It shows great robustness in the computation of the sought
      quantities in SI, especially with signals close to the critical sampling or, on
      the contrary, highly oversampled, situations where the background elimination by
      EMD is the most prone to errors.

PMID- 22139262
TI  - Crystalline Pr:SrAl12O19 waveguide laser in the visible spectral region.
AB  - We fabricated waveguides in Pr:SrAl(12)O(19) crystals by direct femtosecond laser
      writing. The propagation losses were calculated to be as low as 0.16 dB/cm at a
      wavelength of 633 nm. Laser oscillation in a diode-pumped waveguide at a
      wavelength of 643.5 nm was realized. The output power of the waveguide laser was
      28.1 mW at a slope efficiency of 8%.

PMID- 22139263
TI  - Modulational instability in a passive fiber cavity, revisited.
AB  - Modulation instability in a passive fiber cavity is revisited. We address the
      problem in the statement with a continuous-time Ikeda map, rather than in the
      mean-field limit. It is found that plane wave solutions are unstable for both
      normal and anomalous dispersion regimes of an optical fiber. The origin of the
      instability in the continuous-time Ikeda map is in the mode mixing introduced by
      the beam splitter. The obtained conditions for the instability were compared with
      ones known for the discrete-time Ikeda map, showing appreciable difference,
      which, however reduces in the mean-field limit.

PMID- 22139266
TI  - Dynamics of a semiconductor laser with polarization-rotated feedback and its
      utilization for random bit generation.
AB  - Chaotic semiconductor lasers have been proven attractive for fast random bit
      generation. To follow this strategy, simple robust systems and a systematic
      approach determining the required dynamical properties and most suitable
      conditions for this application are needed. We show that dynamics of a single
      mode laser with polarization-rotated feedback are optimal for random bit
      generation when characterized simultaneously by a broad power spectrum and low
      autocorrelation. We observe that successful random bit generation also is
      sensitive to digitization and postprocessing procedures. Applying the identified
      criteria, we achieve fast random bit generation rates (up to 4 Gbit/s) with
      minimal postprocessing.

PMID- 22139265
TI  - Raman spectroscopy with an integrated arrayed-waveguide grating.
AB  - An integrated arrayed-waveguide grating fabricated in silicon-oxynitride
      technology is applied to Raman spectroscopy. After its validation by reproducing
      the well-known spectrum of cyclohexane, polarized Raman spectra are measured of
      extracted human teeth containing localized initial carious lesions. Excellent
      agreement is obtained between the spectra of healthy and carious tooth enamel
      measured with our integrated device and spectra recorded using a conventional
      Raman spectrometer. Our results represent a step toward the realization of
      compact, hand-held, integrated spectrometers, e.g. for the detection of dental
      caries at an early stage.

PMID- 22139264
TI  - Large-effective-area ten-core fiber with cladding diameter of about 200 MUm.
AB  - A multicore fiber with two-pitch layout is proposed to overcome the trade-off
      between core number and a cladding diameter of a standard hexagonal layout with a
      single-core pitch. A fabricated ten-core fiber simultaneously realizes effective
      area of about 120 MUm(2) at 1550 nm, small crosstalk, and cladding diameter of
      204 MUm. The crosstalk between the center core and outer cores is about 30 dB
      smaller than that between outer cores. The small crosstalk of the center core
      would help to keep the transmission quality of the center core at the same level
      as that of the outer cores.

PMID- 22139267
TI  - Waveguided spoof surface plasmons with deep-subwavelength lateral confinement.
AB  - We present a new type of waveguide scheme for terahertz circuitry based on the
      concept of spoof surface plasmons. This structure is composed of a one
      dimensional array of L-shaped metallic elements horizontally attached to a metal
      surface. The dispersion relation of the surface electromagnetic modes supported
      by this system presents a very weak dependence with the lateral dimension and the
      modes are very deep-subwavelength confined with a long-enough propagation length.

PMID- 22139268
TI  - Tailoring repulsive optical forces in nanophotonic waveguides.
AB  - We describe a mechanism and propose design strategies to selectively tailor
      repulsive-gradient-optical forces between parallel, nanophotonic waveguides via
      morphology augmented by slow-light band-edge modes. We show that at small
      separation lengths, the repulsive force can be made nearly 2 orders of magnitude
      larger than that of standard dielectric waveguides with a square cross section.
      The increased coupling interactions should enable a wider dynamic range of
      optomechanical functionality for potential applications in sensing, switching,
      and nanoelectromechanical systems.

PMID- 22139269
TI  - Tunable 360 degrees  photonic radio frequency phase shifter based on optical
      quadrature double-sideband modulation and differential detection.
AB  - We propose a novel structure of a photonic RF phase shifter based on the vector
      sum principle. The optical signal with quadrature double-sideband modulation
      passes through a dual-output Mach-Zehnder interferometer (MZI), and the two
      outputs are differentially detected. Two phase-quadrature RF terms are generated,
      and their amplitudes can be controlled in a triangularly complementary way by
      changing the phase of the MZI. A full tuning range of 0 degrees -360 degrees  at
      14 GHz is demonstrated experimentally accompanied by nearly constant RF
      amplitude. The validity of using our scheme in all-optical RF phase modulation is
      also verified.

PMID- 22139270
TI  - Electronic speckle pattern interferometry using vortex beams.
AB  - We show that it is possible to perform electronic speckle pattern interferometry
      (ESPI) using, for the first time to our knowledge, vortex beams as the reference
      beam. The technique we propose is easy to implement, and the advantages obtained
      are, among others, environmental stability, lower processing time, and the
      possibility to switch between traditional ESPI and spiral ESPI. The experimental
      results clearly show the advantages of using the proposed technique for
      deformation studies of complex structures.

PMID- 22139274
TI  - Submicrometer organic silica gel fiber for oxygen sensing.
AB  - We introduce the electrospinning method into fabricating oxygen-sensitive
      submicrometer scale optical fiber. Uniform tris (4,7-diphenyl-1,10-phenathroline)
      ruthenium(II) dichloride ([Ru(dpp)(3)](2+)Cl(2))-doped fibers with a diameter of
      900 nm are obtained by electrospinning the organic silicon sol solution derived
      from tetraethyl orthosilicate and n-Octyltriethoxysilane (C(14)H(32)O(3)Si). The
      experimental results show that the single gel fiber exhibits excellent optical
      and sensing properties. A laser with a wavelength of 452 nm can be efficiently
      launched into the fiber and guide along the fiber to excite the fluorescence.
      Then, we find that [Ru(dpp)(3)](2+)-gel fiber has favorable optical and sensing
      characteristics, and the Stern-Volmer plots are linear in the full concentration
      range of O(2) (0-100 vol. %). The ratio of I(0)/I(100), where I(0) and I(100)
      respectively represent the fluorescence intensities of the fiber exposed to 100%
      N(2) and 100% O(2), as the sensitivity of the fiber is 3.5. Simultaneously, the
      fiber can make a quick response within 100 ms. This method provides an effective
      and convenient way to fabricate highly uniform nanoscale or microscale optical
      waveguides for photonic devices.

PMID- 22139275
TI  - Athermal waveguides for optical communication wavelengths.
AB  - We report on the design, fabrication, and characterization of temperature
      insensitive strip silicon-on-insulator racetrack resonators. The influence of
      various parameters, such as waveguide width, waveguide height, ring radius,
      coupling length, ring gap, and operating wavelength, on temperature-dependent
      wavelength shift is examined. A resonant wavelength shift of 0.2 pm/K at a 1550
      nm wavelength is measured for 335 nm * 220 nm waveguides. A significant reduction
      of waveguide propagation losses, improved ring Q value, and higher extinction
      ratio are obtained after overlaying the silicon waveguides with a polymer
      cladding.

PMID- 22139271
TI  - Variations in the point spread function characteristics of wavelengths for a
      wavefront coding imaging system.
AB  - The point spread function (PSF) characteristics of wavelengths for a wavefront
      coding imaging system are investigated. Although the phase delayed by the mask
      changes with wavelength, the shape of the PSF is nearly invariant with respect to
      wavelength. However, the position of the PSF shifts with axial chromatic
      aberration. If the wideband light is separated into several channels and
      separated channel images are restored using the same filter, then color traces
      may be observed in the recombined color images.

PMID- 22139272
TI  - Spatial bandwidth considerations for optical communication through a free space
      propagation link.
AB  - This Letter concentrates on the transverse limitations imposed by a finite
      aperture optical propagation link that supports free space optical communication.
      Here it is assumed that a series of states, which are the spatial component of
      the message, are sent through the communication channel. The spatial bandwidth of
      the propagation link expressed as bits per transmitted photon is computed as the
      product of the average link efficiency times the entropy of the link. To
      facilitate the evaluation, it is assumed that the transmitted states are minimum
      energy loss orbital angular momentum states expressed in the form of
      f(nm)(r)exp(imtheta), where the radial function is controlled to ensure that, for
      each quantum number denoted by the values of n and m, the minimum energy loss is
      obtained. The results illustrate that the bandwidth in units of bits per
      transmitted photon is very nearly equal to log(2)(N(2)(f)here log(2)(.) denotes
      the logarithm in base 2 and the Fresnel number, N(f)=(pi/4)D(1)D(2)/(lambdaz),
      where D(1) is the diameter of the transmitting aperture, D(2) is the diameter of
      the receiving aperture, lambda is the wavelength of the light used, and z is the
      propagation distance.

PMID- 22139273
TI  - Efficient homodyne measurement of picosecond squeezed pulses with pulse shaping
      technique.
AB  - We report on the detection of picosecond pulsed squeezed light generated by an
      optical parametric amplification in a periodically poled MgO:LiNbO(3) waveguide.
      By using a temporally shaped local oscillator in a balanced homodyne detection,
      we obverved the squeezing of -5.0 dB below the shot noise level. The squeezing
      level at the exit of the waveguide was estimated to be -9.7+/-0.8 dB.

PMID- 22139276
TI  - Hydrophobic photonic crystal fibers.
AB  - We propose and demonstrate hydrophobic photonic crystal fibers (PCFs). A chemical
      surface treatment for making PCFs hydrophobic is introduced. This repels water
      from the holes of PCFs, so that their optical properties remain unchanged even
      when they are immersed in water. The combination of a hollow core and a water
      repellent inner surface of the hydrophobic PCF provides an ultracompact dissolved
      gas sensor element, which is demonstrated for the sensing of dissolved ammonia
      gas.

PMID- 22139279
TI  - Fiber-based Bessel beams with controllable diffraction-resistant distance.
AB  - We experimentally generate n=0 Bessel beams via higher-order cladding mode
      excitation with a long period fiber grating. Our method allows >99% conversion
      efficiency, wide or narrow conversion bandwidth, and accurate control of the
      number of rings in the beam. This latter property is equivalent to tuning the
      beam cone angle and allows for control of width and propagation distance of the
      center spot. We generate Bessel-like beams from LP(0,5) to LP(0,15) cladding
      modes and measure their propagation-invariant characteristics as a function of
      mode order, which match numerical simulations and a simple geometric model. This
      yields a versatile tool for tuning depth of focus out of fiber tips, with
      potential uses in endoscopic microscopy.

PMID- 22139280
TI  - Nonlinear response of GaAs gratings in the extraordinary transmission regime.
AB  - We theoretically describe a way to enhance harmonic generation from subwavelength
      slits milled on semiconductor substrates in strongly absorptive regimes. The
      metal-like response typical of semiconductors, like GaAs and GaP, triggers
      enhanced transmission and nonlinear optical phenomena in the deep UV range. We
      numerically study correlations between linear and nonlinear responses and their
      intricacies in infinite arrays, and highlight differences between nonlinear
      surface and magnetic sources, and intrinsic chi((2)) and chi((3)) contributions
      to harmonic generation. The results show promising efficiencies at wavelengths
      below 120 nm, and reveal coupling of TE and TM polarizations for pump and
      harmonic signals. A downconversion process that can regenerate pump photons with
      polarization orthogonal to the incident pump is also discussed.

PMID- 22139281
TI  - Real-time quantitative phase imaging with a spatial phase-shifting algorithm.
AB  - This Letter reports on the use of a spatial phase-shifting algorithm in a fast,
      straightforward method of real-time quantitative phase imaging. The computation
      time for phase extraction is five times faster than a Fourier transform and twice
      as fast as a Hilbert transform. The fact that the phase extraction from an
      interferogram of 512 * 512 pixels takes less than 8.93 ms with a typical desktop
      computer suggests the proposed method can be readily applied to high-speed
      dynamic quantitative phase imaging. The proposed method of quantitative phase
      imaging is effective and sufficiently general for application to the dynamic
      phenomena of biological samples.

PMID- 22139278
TI  - Ultrahigh-contrast and wideband nanoscale photonic crystal all-optical diode.
AB  - We experimentally realize a nanoscale all-optical diode in a photonic crystal
      heterostructure with broken spatial inversion symmetry, performing independent of
      optical nonlinearity. The physical mechanism lies in unique dispersion relations
      of the photonic crystal and the transition of incident light between different
      electromagnetic Bloch modes. An ultrahigh transmission contrast of 10(3) order, a
      large operating bandwidth of over 50 nm, and an ultralow photon intensity of less
      than 10 kW/cm(2) are reached simultaneously.

PMID- 22139277
TI  - Nonlinear phase dispersion spectroscopy.
AB  - Nonlinear phase dispersion spectroscopy is introduced as a means to retrieve
      wideband, high spectral resolution profiles of the wavelength-dependent real part
      of the refractive index. The method is based on detecting dispersion effects
      imparted to a light field with low coherence transmitted through a thin sample
      and detected interferometrically in the spectral domain. The same sampled signal
      is also processed to yield quantitative phase maps and spectral information
      regarding the total attenuation coefficient using spectral-domain phase
      microscopy and spectroscopic optical coherence tomography (SOCT), respectively.
      Proof-of-concept experiments using fluorescent and nonfluorescent polystyrene
      beads and another using a red blood cell demonstrate the ability of the method to
      quantify various absorptive/dispersive features. The increased sensitivity of
      this method, novel to our knowledge, is compared to intensity-based spectroscopy
      (e.g., SOCT), and potential applications are discussed.

PMID- 22139283
TI  - Angular and radial mode analyzer for optical beams.
AB  - We describe an approach to determining both the angular and the radial modal
      content of a scalar optical beam in terms of optical angular momentum modes. A
      modified Mach-Zehnder interferometer that incorporates a spatial rotator to
      determine the angular modes and an optical realization of the fractional Hankel
      transform (fHT) to determine the radial modes is analyzed. Varying the rotation
      angle and the order of the fHT produces a two-dimensional (2D) interferogram from
      which we extract the modal coefficients by simple 2D Fourier analysis.

PMID- 22139284
TI  - Operation of Brillouin dynamic grating in single-mode optical fibers.
AB  - The first (to our knowledge) observation of Brillouin dynamic grating in
      conventional single-mode fibers is reported, and the characterization is
      demonstrated with respect to the external parameters for the grating generation.
      When a 100 m single-mode fiber is used, a reflectance of 8% with a spectral
      bandwidth as low as 2.4 MHz is achieved, which is less than 10% of ordinary
      Brillouin gain bandwidth.

PMID- 22139282
TI  - Backscatter tolerant squeezed light source for advanced gravitational-wave
      detectors.
AB  - We report on the performance of a dual-wavelength resonant, traveling-wave
      optical parametric oscillator to generate squeezed light for application in
      advanced gravitational-wave interferometers. Shot noise suppression of 8.6+/-0.8
      dB was measured across the detection band of interest to Advanced LIGO, and
      controlled squeezing measured over 5900 s. Our results also demonstrate that the
      traveling-wave design has excellent intracavity backscattered light suppression
      of 47 dB and incident backscattered light suppression of 41 dB, which is a
      crucial design issue for application in advanced interferometers.

PMID- 22139285
TI  - Optical fiber probe based on spherical coupling of light energy for inner
      dimension measurement of microstructures with high aspect ratios.
AB  - An optical fiber probe, based on spherical coupling of light energy, is proposed
      to transform the lateral displacement of a spherical coupler into the deflection
      of a light energy center, while the light energy is transmitted in the reverse
      direction. Therefore, the shadowing effect of a microcavity can be eliminated.
      The probe has a high displacement sensitivity, allowing precision inner-dimension
      measurements of microstructures with high aspect ratios. Measurements of
      microholes and fuel injection nozzles indicate that, for a microstructure with an
      aspect ratio of up to 15:1, a probing force <1 MUN, a resolution of up to 0.05
      MUm can be achieved using the proposed probe, which is easy to exchange and low
      cost.

PMID- 22139287
TI  - Femtosecond laser tuning of silicon microring resonators.
AB  - Femtosecond laser modification is demonstrated as a possible method for
      postfabrication tuning of silicon microring resonators. Single 400 nm femtosecond
      laser pulses were used to modify the effective index of crystalline silicon
      microring waveguides by either amorphization or surface nanomilling depending on
      the laser fluence. Both blue- and redshifts in the microring resonance could be
      achieved without imparting significant degradation to the device quality factor.

PMID- 22139288
TI  - Colored image produced with guided-mode resonance filter array.
AB  - A method to reproduce colored images with a guided-mode resonance filter (GMRF)
      array is presented in this Letter. Because of their excellent characteristics,
      monochromatic light of the three primary colors with high purity can be achieved
      by using GMRF structures. Moreover, the primary colors are obtained without
      changing other GMRF parameters except the period, which could be realized easily
      with laser direct writing technology. The result shows that a colored image with
      high resolution and verisimilitude can be reproduced.

PMID- 22139289
TI  - Adaptive double-sided fluidic lens of polydimethylsiloxane membranes of matching
      thickness.
AB  - A fluidic lens with double-sided polydimethylsiloxane membranes of different
      thicknesses that complement each other to reduce spherical aberration was
      fabricated. It is operated with magnetic repulsion induced by the current in the
      voice coil. The optical power of the proposed lens was observed to be
      considerably higher compared to that of a typical convex glass lens. The focal
      lengths of rays passing through the optical axis and the edge of the lens was
      measured and compared with the simulation data. The spherical aberration of the
      proposed lens was observed to be negligibly small compared to that of a plano
      convex lens.

PMID- 22139292
TI  - Wavelength-selective 4 * 4 nonblocking silicon optical router for networks-on
      chip.
AB  - We design and fabricate a wavelength-selective nonblocking 4 * 4 silicon optical
      router based on microring resonator for use in future integrated photonic
      interconnection networks. We successfully demonstrate 12 possible I/O routing
      paths and present 13 nonblocking operating states, including four broadcasting
      states, with worst-case extinction ratio and cross talk of 21.05 and -21.56 dB,
      respectively. Thermal tuning is employed to compensate the resonance shift of
      microring resonators caused by fabrication errors and adjust the resonance to
      match the International Telecommunication Unit grid with the channel spacing of
      100 GHz.

PMID- 22139286
TI  - In vivo confocal imaging of fast intrinsic optical signals correlated with frog
      retinal activation.
AB  - Using freshly isolated animal retinas, we have conducted a series of experiments
      to test fast intrinsic optical signals (IOSs) that have time courses comparable
      to electrophysiological kinetics. In this Letter, we demonstrate the feasibility
      of in vivo imaging of fast IOSs in intact frogs. A rapid line-scan confocal
      ophthalmoscope was constructed to achieve high-speed IOS recording. By rejecting
      out-of-focus background light, the line-scan confocal imager provided the
      resolution to differentiate individual photoreceptors in vivo. Rapid confocal
      imaging disclosed robust IOSs with time courses comparable to retinal
      electroretinogram kinetics. High-resolution IOS images revealed both positive
      (increasing) and negative (decreasing) light responses, with subcellular
      complexity.

PMID- 22139293
TI  - Long-range surface plasmon polaritons propagating on a dielectric waveguide
      support.
AB  - In the traditional long-range surface plasmon geometry, an ultrathin metal film
      is sandwiched between two layers having identical dielectric constants. Here we
      demonstrate the long-range surface plasmon polariton (LRSPP) properties for a new
      structure where a thin layer with a dielectric constant exceeding that of the
      surroundings is inserted within the sandwich, provided the layer thickness d
      satisfies the condition k(?)d=mpi where k(?) is the component of the guide
      wavevector perpendicular to the layer and m is an integer. The resulting plasmon
      modes have smaller losses and nearly the same phase velocity as the original
      LRSPP. This provides a strategy to support silver films having thicknesses of
      10's of nanometers to create plasmonic devices for sensor applications.

PMID- 22139295
TI  - Effect of coherence and polarization on frequency resolution in optical Fourier
      transforming system.
AB  - Using an example of vector Gaussian Schell-model beam, we demonstrate and analyze
      the dependence of the spatial frequency resolution in optical Fourier
      transforming system on the intrinsic coherence-polarization structure of
      illumination.

PMID- 22139290
TI  - Laplace field microscopy for label-free imaging of dynamic biological structures.
AB  - We present Laplace field microscopy as a method for generating intrinsic contrast
      of transparent specimens. This technique uses a spatial light modulator to
      perform the Laplacian of the field in the Fourier plane of a microscope image.
      The resulting image incorporates phase information and thus renders high contrast
      images from phase objects. We demonstrate the potential of the method by imaging
      index-matched beads, unlabeled tissue slices, and dynamic live cells.

PMID- 22139296
TI  - Toxic and essential trace metals in first baby haircuts and mother hair from Imam
      Hossein Hospital Tehran, Iran.
AB  - Hair metal level in newborn and mother pairs from Iran is reported. Toxic metals
      including cadmium (157 vs. 87.5 MUg/kg), mercury (246 vs. 198 MUg/kg), copper
      (14,313 vs. 11,776 MUg/kg) and aluminum (52,022 vs. 408,207 MUg/kg) were higher
      in newborn hair when compared to their mothers; suggesting that metals maybe
      discarded in the fetus as a detoxification method. Comparison with available data
      from Germany and Poland, and Iraq suggests overall similarities and significant
      differences in the case of the Iraqi subjects. Public protection from mixture
      toxicity of metals will be facilitated by studies such as ours.

PMID- 22139291
TI  - Cataract diagnosis by measurement of backscattered light.
AB  - We present a portable optical cataract assessment technology which measures with
      a circular photodetector the fraction of light scattered backwards by the human
      eye lens when illuminated by a laser diode. As our signal arises directly from
      the fundamental pathology-increased scattering in the lens-it directly assesses
      cataract extent and progression. Initial clinical results in undilated human eyes
      show device reading correlations in agreement with clinical examination and
      Scheimpflug photography.

PMID- 22139297
TI  - Pesticides residues and metals in plant products from agricultural area of
      Belgrade, Serbia.
AB  - The objective of study was to assess the levels of selected metals and pesticides
      in plant products from agricultural area of Belgrade, Serbia in order to indicate
      their possible sources and risks of contamination and to evaluate their sanitary
      probity and safety. The concentrations of cadmium, copper, iron, manganese,
      nickel, lead and zinc were below limits established by national and international
      regulations (maximum found concentrations were 0.028, 1.91, 11.16, 1.77, 0.605,
      0.073 and 1.76 mg kg(-1) respectively). Only residue of one of examined
      pesticides was found in amount below MRL (bifenthrin 2.46 MUg kg(-1)) in only one
      of analysed samples, while others were below detection limits. Obtained results
      indicate that crops from examined agricultural areas are unpolluted by
      contaminants used for plant protection and nutrition, indicating good
      agricultural practice regarding pesticides and fertilizer usage as well as
      moderate industrial production within examined areas.

PMID- 22139294
TI  - Imaging high-frequency periodic motion in the mouse ear with coherently
      interleaved optical coherence tomography.
AB  - Vibratory measurements of the structures of the ear are key to understanding much
      of the pathology in mouse models of hearing loss. Unfortunately the high-speed
      sampling required to interrogate the high end of the mouse hearing spectrum is
      beyond the reach of most optical coherence tomography (OCT) systems. To address
      this issue, we have developed an algorithm that enables phase-sensitive OCT
      measurements over the full range of the mouse hearing spectrum (4-90 kHz). The
      algorithm phase-locks the line-trigger to the acoustic stimulation and then uses
      interleaved sampling to reconstruct the signal with higher temporal sampling. The
      algorithm was evaluated by measuring the vibratory response of mouse tympanic
      membrane to a pure tone stimulus.

PMID- 22139298
TI  - Nogo-66 receptor activation inhibits neurite outgrowth and increases beta-amyloid
      protein secretion of cortical neurons.
AB  - A Nogo-A to Nogo-66 receptor (NgR) pathway is well known to contribute to the
      inhibition of the neurite regeneration of adult central nervous system neurons
      after traumatic injuries. Recent evidence suggests that Nogo-A and NgR are
      involved in the pathology of Alzheimer's disease (AD), as evidenced by the fact
      that Nogo-A is overexpressed by hippocampal neurons in patients with AD and is
      associated with beta-amyloid protein (Abeta) deposits in senile plaques. In the
      present experiments, we investigated the potential role of Nogo-A in both neurite
      outgrowth and Abeta generation in cortical neurons. Our results showed that
      activation of NgR not only inhibited neurite outgrowth in cortical neurons by
      activating the rho-associated coiled coil-containing protein kinase (ROCK) and
      protein kinase C, but also promoted their Abeta secretion, which was at least in
      part activated by ROCK. These findings suggest that the overexpression of Nogo-A
      and the activation of NgR inhibit neurite outgrowth and alter neuronal
      metabolism, resulting in overproduction and/or release of Abeta, which in turn
      may trigger the onset and development of AD. Inhibition of ROCK can promote
      neurite outgrowth and reduce Abeta production of cortical neuron, which suggests
      that ROCK appears to be a good target for AD therapy.

PMID- 22139300
TI  - Characterizations of particle-bound trace metals and polycyclic aromatic
      hydrocarbons (PAHs) within Tibetan tents of south Tibetan Plateau, China.
AB  - INTRODUCTION: Exposure to trace metals and polycyclic aromatic hydrocarbons
      (PAHs) adsorbed on particulates is of a serious health concern. Levels of some
      trace metals in total suspended particulate and 13 PAHs of fine particulate
      matter were measured from nomadic tents in the southern Tibetan Plateau in summer
      2010. RESULTS AND DISCUSSION: The indoor air within the tents was seriously
      polluted, mainly due to yak dung combustion. Average trace metal concentrations
      were much higher (range of indoor/outdoor ratio 61-291) than those of the outdoor
      air. Additionally, enrichment factors of most trace metals of indoor air were
      similar to those of outdoor air, indicating outdoor air quality of the studied
      area was possibly influenced by pollutants emitted from local tents. Mean
      concentrations of total PAHs and BaP within tents was 5372.45 and 364.79 ng/m(3),
      hundred times higher than that of outdoor air of the Tibetan Plateau. Three- and
      four-ring PAHs were the predominant components. The diagnostic ratio of BaA/(BaA
      + Chr) was 0.33. Since Tibetan women typically spend longer time within the
      tents, they were exposed to PAHs (BaP exposure = 1.81 MUg/m(3)) about two times
      of other family members. Among all the PAHs, Bap contributed the most (82.6%) of
      the total carcinogenicity. Similarly, the excess lifetime cancer risk for women
      and other family members were 2.75 * 10(-4) and 1.27 * 10(-4), respectively,
      indicating Tibetan herdsmen, especially women who are in charge of most house
      chores were at risk for adverse health effects.

PMID- 22139299
TI  - Bioremediation of industrial effluents containing heavy metals using brewing
      cells of Saccharomyces cerevisiae as a green technology: a review.
AB  - The release of heavy metals into the environment, mainly as a consequence of
      anthropogenic activities, constitutes a worldwide environmental pollution
      problem. Unlike organic pollutants, heavy metals are not degraded and remain
      indefinitely in the ecosystem, which poses a different kind of challenge for
      remediation. It seems that the "best treatment technologies" available may not be
      completely effective for metal removal or can be expensive; therefore, new
      methodologies have been proposed for the detoxification of metal-bearing
      wastewaters. The present work reviews and discusses the advantages of using
      brewing yeast cells of Saccharomyces cerevisiae in the detoxification of
      effluents containing heavy metals. The current knowledge of the mechanisms of
      metal removal by yeast biomass is presented. The use of live or dead biomass and
      the influence of biomass inactivation on the metal accumulation characteristics
      are outlined. The role of chemical speciation for predicting and optimising the
      efficiency of metal removal is highlighted. The problem of biomass separation,
      after treatment of the effluents, and the use of flocculent characteristics, as
      an alternative process of cell-liquid separation, are also discussed. The use of
      yeast cells in the treatment of real effluents to bridge the gap between
      fundamental and applied studies is presented and updated. The convenient
      management of the contaminated biomass and the advantages of the selective
      recovery of heavy metals in the development of a closed cycle without residues
      (green technology) are critically reviewed.

PMID- 22139301
TI  - De-regulation of the RBBP6 isoform 3/DWNN in human cancers.
AB  - Retinoblastoma binding protein 6 (RBBP6) is a nuclear protein, previously
      implicated in the regulation of cell cycle and apoptosis. The human RBBP6 gene
      codes for three protein isoforms and isoform 3 consists of the domain with no
      name domain only whilst the other two isoforms, 1 and 2 comprise of additional
      zinc, RING, retinoblastoma and p53 binding domains. In this study, the
      localization of RBBP6 using RBBP6 variant 3 mRNA-specific probe was performed to
      investigate the expression levels of the gene in different tumours and find a
      link between RBBP6 and human carcinogenesis. Using FISH, real-time PCR and
      Western blotting analysis our results show that RBBP6 isoform 3 is down-regulated
      in human cancers. RBBP6 isoform 3 knock-down resulted in reduced G2/M cell cycle
      arrest whilst its over-expression resulted in increased G2/M cell cycle arrest
      using propidium iodide DNA staining. The results further demonstrate that the
      RBBP6 isoform 3 may be the cell cycle regulator and involved in mitotic apoptosis
      not the isoform 1 as previously reported for mice. In conclusion, these findings
      suggest that RBBP6 isoform 3 is a cell cycle regulator and may be de-regulated in
      carcinogenesis.

PMID- 22139305
TI  - Quality improvement and accreditation readiness in state public health agencies.
AB  - OBJECTIVE: There were 3 specific objectives of this study. The first objective
      was to examine the progress of state/territorial health assessment, health
      improvement planning, performance management, and quality improvement (QI)
      activities at state/territorial health agencies and compare findings to the 2007
      findings when available. A second objective was to examine respondent interest
      and readiness for national voluntary accreditation. A final objective was to
      explore organizational factors (eg, leadership and capacity) that may influence
      QI or accreditation readiness. DESIGN: Cross-sectional study. SETTING: State and
      Territorial Public Health Agencies. PARTICIPANTS: Survey respondents were
      organizational leaders at State and Territorial Public Health Agencies. RESULTS:
      Sixty-seven percent of respondents reported having a formal performance
      management process in place. Approximately 77% of respondents reported a QI
      process in place. Seventy-three percent of respondents agreed or strongly agreed
      that they would seek accreditation and 36% agreed or strongly agreed that they
      would seek accreditation in the first 2 years of the program. In terms of
      accreditation prerequisites, a strategic plan was most frequently developed,
      followed by a state/territorial health assessment and health improvement plan,
      respectively. CONCLUSIONS: Advancements in the practice and applied research of
      QI in state public health agencies are necessary steps for improving performance.
      In particular, strengthening the measurement of the QI construct is essential for
      meaningfully assessing current practice patterns and informing future programming
      and policy decisions. Continued QI training and technical assistance to agency
      staff and leadership is also critical. Accreditation may be the pivotal factor to
      strengthen both QI practice and research. Respondent interest in seeking
      accreditation may indicate the perceived value of accreditation to the agency.

PMID- 22139307
TI  - Standardizing environmental health processes at the Iowa Department of Public
      Health.
AB  - Standardized work is the foundation of continuous improvement. Documenting
      standard processes is a precursor to problem solving and allows an organization
      to understand work flow, measure performance, and identify opportunities for
      improvement. Environmental health is an important function of public health
      departments but is rarely studied systematically. This article describes
      documentation of standard processes, identification of improvement opportunities,
      and lessons learned for environmental health processes at the Iowa Department of
      Public Health, using a pilot group of 3 local county offices. The approach
      described in this article can serve as a template for other states to follow in
      their quality improvement journeys.

PMID- 22139308
TI  - Using quality improvement to promote breast-feeding in a local health department.
AB  - In 2008, breast-feeding initiation and continuation rates in Beaufort County,
      North Carolina, were lower than statewide rates. A quality improvement (QI)
      project was initiated to increase breast-feeding rates by enhancing the overall
      environment that supports breast-feeding at the Beaufort County Health
      Department. This case study describes one of the first QI initiatives implemented
      through the North Carolina Center for Public Health Quality QI training program,
      conducted in 2009. The aim of this project was to improve the health and wellness
      of mothers and infants in Beaufort County by promoting breast-feeding among
      Beaufort County Health Department Women, Infants and Children (WIC) clients.
      Using QI tools, 4 new approaches to breast-feeding promotion were tested and
      implemented: creating a nurturing location to breast-feed while at the health
      department, actively telephoning new mothers to provide breast-feeding support,
      incentivizing adoption of educational messages by providing a breast-feeding tote
      bag, and promoting new WIC food packages. These enhancements involved staff in QI
      planning and implementation and correlated with improved breast-feeding
      initiation for WIC clients during the year following project completion.

PMID- 22139310
TI  - Applying Lean principles and Kaizen rapid improvement events in public health
      practice.
AB  - This case study describes a local home health and hospice agency's effort to
      implement Lean principles and Kaizen methodology as a rapid improvement approach
      to quality improvement. The agency created a cross-functional team, followed Lean
      Kaizen methodology, and made significant improvements in scheduling time for home
      health nurses that resulted in reduced operational costs, improved working
      conditions, and multiple organizational efficiencies.

PMID- 22139303
TI  - Senescent endothelial dysfunction is attributed to the up-regulation of
      sphingosine-1-phosphate receptor-2 in aged rats.
AB  - Sphingosine-1-phosphate (S1P) regulates an array of biological activities in
      various cell types. Many S1P-regulated functions are mediated by S1P receptor
      subtypes. Previous studies have shown that the S1P receptor-2 (S1P(2) receptor)
      is involved in senescence of endothelial cells in vitro. However, the functional
      outcomes of S1P(2) receptor-mediated signaling pathways in a physiological
      environment are currently unknown. The main aim of this study was to explore the
      underlying mechanisms of senescent-associated impairments in pulmonary
      microvascular endothelial cells (PMECs) isolated from young and aged rats in
      vivo. The expression of S1P receptor subtypes in PMECs was detected using RT-PCR
      and Western blot analyses. The chemotaxis of PMECs was measured using the
      transwell migration assay. The endothelial morphogenesis assay was performed in
      three-dimensional Matrigel. The wound-healing assay was performed using a scratch
      wound model on primary PMEC monolayers. We observed that the S1P(2) receptor was
      markedly increased and S1P-regulated responses were significantly inhibited in
      PMECs isolated from aged rats. Furthermore, the senescent-associated impairments
      were revoked by the down-regulation of the S1P(2) receptor in senescent PMECs.
      These results indicate that the impaired functions (such as chemotactic, wound
      healing, and morphogenetic responses) in senescent PMECs in vivo are mediated by
      the S1P(2) receptor.

PMID- 22139313
TI  - Why Don Berwick is almost right: how public health quality improvement operates
      within complex systems.

PMID- 22139306
TI  - Applying the model for improvement in a local health department: quality
      improvement as an effective approach in navigating the changing landscape of
      public health practice in Buncombe County, North Carolina.
AB  - In local health departments across the nation, problem solving and rapid change
      occur every day. Often, the results of these changes or problem-solving
      techniques may not be studied or evaluated fully to determine whether desired
      results were achieved. In fact, program evaluation, research, and technical
      assistance at the local level may be reduced or eliminated in many states during
      a time of rapidly diminishing resources and increasing demand for public health
      services. In delivering population-level programs, quality improvement (QI)
      methods may provide a much-needed alternative and more efficient approach than
      traditional research and evaluation to help answer public health practice
      questions such as "How do we know when a project or program really works, and,
      more importantly, how can we do it better?" This article focuses on the Buncombe
      County Department of Health's (BCDH's) experience utilizing a QI approach called
      the model for improvement (MFI), incorporating plan-do-study-act cycles and small
      tests of change, on a specific H1N1 influenza-awareness public health
      preparedness communication project. In addition, results of the BCDH's
      participation in QI initiatives and training resulted in success implementing
      change in other areas of the health department including decreasing wait time and
      addressing a backlog of prenatal visit appointments from 54 to 15 days, and more
      than doubling prenatal history efficiency uptake in a 5-week period. These case
      studies in the BCDH present how the MFI introduced the foundation of a culture of
      continuous QI within the organization.

PMID- 22139314
TI  - Understanding and controlling variation in public health.
AB  - Variation in work processes is a critically important concept and method for
      creating true and sustainable improvement in public health services and
      activities. This article describes the concept of variation based on W. Edwards
      Deming's profound knowledge and defines basic terms such as common cause and
      special cause variation. Control charts are explained as the primary tool for
      calculating variation within work processes. The article also provides an example
      of how variation theory can be applied to create sustainable improvement in
      public health.

PMID- 22139302
TI  - An essential role for the Id1/PI3K/Akt/NFkB/survivin signalling pathway in
      promoting the proliferation of endothelial progenitor cells in vitro.
AB  - The enhancement of re-endothelialisation is a critical therapeutic option for
      repairing injured blood vessels. Endothelial progenitor cells (EPCs) are the
      major source of cells that participate in endothelium repair and contribute to re
      endothelialisation by reducing neointima formation after vascular injury. The
      over-expression of the inhibitor of differentiation or DNA binding 1 (Id1)
      significantly improved EPC proliferation. This study aimed to investigate the
      effects of Id1 on the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor
      kappa B (NFkappaB)/survivin signalling pathway and its significance in promoting
      EPC proliferation in vitro. Spleen-derived EPCs were cultured as previously
      described. Id1 was presented at low levels in EPCs, and was rapidly up-regulated
      by stimulation with vascular endothelial growth factor. We demonstrated that
      transient transfection of Id1 into EPCs activated the PI3K/Akt/NFkappaB/survivin
      signalling pathway and promoted EPC proliferation. The proliferation of EPCs was
      extensively inhibited by silencing of endogenous Id1, and knockdown of Id1
      expression led to suppression of PI3K/Akt/NFkappaB/survivin signalling pathway in
      EPCs. In addition, blockade by the PI3K-specific inhibitor LY294002, Akt
      inhibitor, the NFkappaB inhibitor BAY 11-7082, the survivin inhibitor Curcumin,
      or the survivin inhibitor YM155 reduced the effects of Id1 transfection. These
      results suggest that the Id1/PI3K/Akt/NFkappaB/survivin signalling pathway plays
      a critical role in EPC proliferation. The Id1/PI3K/Akt/NFkappaB/survivin
      signalling pathway may represent a novel therapeutic target in the prevention of
      restenosis after vascular injury.

PMID- 22139309
TI  - Early evaluation results from a statewide quality improvement training program
      for local public health departments in North Carolina.
AB  - CONTEXT: Many state and local public health agencies have developed accreditation
      systems and are utilizing quality improvement (QI) methods and tools to improve
      the public health infrastructure. Development of strategies to support and build
      the capacity of the public health workforce to apply QI can help advance these
      efforts. OBJECTIVE: This article describes the adaptation and creation of a
      standardized QI training program for local health departments (LHDs), explores
      the effectiveness of the program in increasing the confidence of the LHD staff to
      apply QI methods and tools, and discusses lessons learned from the first cohort
      of the program. METHODS: An existing program designed for health care
      professionals was pilot tested, adapted, and used in 8 LHDs. A formative
      evaluation of the new public health QI training program was conducted through a
      hybrid internal and external evaluation model. Pre/postsurveys were used to
      measure participant satisfaction and the capacity of LHD staff to conduct QI.
      RESULTS: Staff from 8 LHDs successfully completed the program and 94% of
      participants reported that they were satisfied with the overall training program.
      Seventy percent of participants reported a higher perceived confidence in
      conducting a QI project, and all participants reported sharing QI tools and
      methods with their coworkers. CONCLUSION: These findings suggest that QI training
      programs using methods and tools previously applied in health care and other
      industries can be successfully adapted to public health. Although additional
      studies are needed to validate the results, this training model can be used to
      inform future work in developing a standardized QI training program in public
      health.

PMID- 22139311
TI  - Lessons learned from building a culture and infrastructure for continuous quality
      improvement at Cabarrus Health Alliance.
AB  - This case study describes a local public health agency's multiyear effort to
      establish an infrastructure and organizational culture for continuous quality
      improvement, using data from interviews with the agency's senior leaders,
      managers, and frontline staff. Lessons learned include the importance of setting
      stretch goals, engaging leaders at all levels of the organization, empowering
      frontline staff to make changes, providing quality improvement training for staff
      and leaders, starting with small projects first, spreading quality improvement
      efforts to involve all parts of the agency, and sustaining momentum by creating a
      supporting infrastructure for continuous quality improvement and continually
      initiating new projects.

PMID- 22139304
TI  - Genetic, environmental and epigenetic influences on variation in human tooth
      number, size and shape.
AB  - The aim of this review is to highlight some key recent developments in studies of
      tooth number, size and shape that are providing better insights into the roles of
      genetic, environmental and epigenetic factors in the process of dental
      development. Advances in molecular genetics are helping to clarify how epigenetic
      factors influence the spatial and temporal regulation of the complex processes
      involved in odontogenesis. At the phenotypic level, the development of
      sophisticated systems for image analysis is enabling new dental phenotypes to be
      defined. The 2D and 3D data that are generated by these imaging systems can then
      be analysed with mathematical approaches, such as geometric morphometric
      analysis. By gathering phenotypic data and DNA from twins, it is now possible to
      use 'genome-wide' association studies and the monozygotic co-twin design to
      identify important genes in odontogenesis and also to clarify how epigenetic and
      environmental factors can affect this process. Given that many of the common
      dental anomalies affecting the human dentition are interrelated, apparently
      reflecting pleiotropic genetic effects, the discoveries and new directions
      described in this paper should have important implications for clinical dental
      practice in the future.

PMID- 22139315
TI  - Assessing quality improvement in local health departments: results from the Multi
      State Learning Collaborative.
AB  - OBJECTIVE: This study examined changes in quality improvement: (1) over a 3-year
      period, (2) among mini-collaborative participants, and (3) among agencies that
      were classified in the lowest QI performance quartile. METHODS: : A QI Maturity
      Tool was administered to all local health departments in the Multi-State Learning
      Collaborative states. Factorial ANOVA was performed to determine differences in
      composite factor scores and interaction effects were explored. RESULTS: : The
      results revealed a significant increase in the percent of agencies that reported
      ever implementing a formal QI process from 2009 to 2011 and agencies that
      participated in a mini-collaborative were more likely than their non-mini
      collaborative counterparts to report QI implementation. The findings also
      suggested significant changes in QI capacity and competency as well as alignment
      and spread over the course of the grant, among mini-collaborative participants,
      and among agencies that were originally identified in the lowest QI maturity
      quartile. No significant changes in organizational culture were revealed by year
      or among mini-collaborative participants. However, agencies in the lowest
      quartile saw significant changes in organizational culture during the project
      period. CONCLUSIONS: Significant changes in specific QI domains are possible to
      detect during a 3-year period. Our research gives us confidence that the QI
      Maturity Tool measures the right domains and is an important contribution to
      quantifying the adoption and spread of QI in public health. However, further
      refinement is needed to better standardize language and definitions of the
      component parts of a QI system.

PMID- 22139312
TI  - A local health department's journey to the summit: a case study of a decade of
      quality improvement.
AB  - As the interest in quality improvement (QI) efforts in public health agencies
      gathers momentum, organizations looking to initiate or strengthen QI processes
      may benefit from learning about existing programs. This article serves as a case
      study for other agencies to consider as they embark upon their QI journey.
      Specifically, this article reviews more than a decade of QI efforts in a mid
      sized local health department and highlights areas of success (including an
      annual QI summit), barriers to implementation of QI, and areas needing
      improvement.

PMID- 22139317
TI  - A quality improvement initiative to enhance public health workforce capabilities.

PMID- 22139318
TI  - Coaching for development:  an essential leadership tool.

PMID- 22139316
TI  - Quality improvement learning collaboratives in public health:  findings from a
      multisite case study.
AB  - OBJECTIVES: This study was designed to (1) test a theory on the key drivers of a
      successful mini-collaborative, (2) describe the application of quality
      improvement (QI) approaches and techniques among mini-collaborative participants,
      and (3) identify key attributes that affect the spread and sustainability of QI
      efforts within a local public health agency. METHODS: A multisite case study
      methodology was used to evaluate a subset of mini-collaboratives and their
      participating local health departments that were working in specific target
      areas. Data were collected during semistructured interviews and while observing
      mini-collaborative meetings. Documentation reviews were also conducted. We used
      standard techniques to code the data on the basis of themes and connections
      between themes. RESULTS: The findings provide early evidence that support our
      case study theory on the drivers of a successful mini-collaborative including
      advanced planning, the selection of faculty, timely training and technical
      assistance, the role of senior leaders, the application of evidence-based
      practices, the use of an improvement model, evaluation efforts, communication,
      the availability of resources, target selection, and prior experience with and
      application of QI. While the case studies provided limited evidence of
      sustainability and broad spread of QI within participating states, mini
      collaboratives appear to have had a major impact and will likely influence the
      work of participating local health departments going forward. CONCLUSIONS: Our
      findings suggest that the mini-collaboratives served as a catalyst for engaging
      local health departments in the theory and practice of QI.

PMID- 22139319
TI  - Effectiveness of public health quality improvement training approaches: 
      application, application, application.
AB  - CONTEXT: Quality improvement (QI) has been identified as a key strategy to
      improve the performance of state and local public health agencies. Quality
      improvement training effectiveness has received little attention in the
      literature. OBJECTIVES: To evaluate the effectiveness of 3 QI training types:
      webinars, workshops, and demonstration site activities on improving participant
      knowledge, skill, and ability to conduct QI through a questionnaire conducted
      after training participation. DESIGN: We used a natural experimental design
      hypothesizing that demonstration site participants would have the greatest gains
      on outcomes of interest compared with webinar and workshop participants.
      Bivariate and multivariate models were used to examine outcome differences
      between questionnaire respondents who participated in various training types.
      PARTICIPANTS: Local health department employees who participated in the 3
      training strategies. MAIN OUTCOME MEASURES: Measures included knowledge and skill
      gain, skill application, QI receptivity, and ability to successfully participate
      in a QI project. RESULTS: Two hundred eighty-four unique individuals who work in
      143 health departments completed the questionnaire for a 59% response rate. The
      majority of these health departments serve midsize populations. Demonstration
      site respondents had significantly greater gains in knowledge and skills, skill
      application, and ability to successfully participate in a QI project. Webcast
      training participants had significantly higher QI receptivity in adjusted models.
      Respondents who participated in both webcast and demonstration site trainings had
      higher mean scores on all outcomes when compared with demonstration site single
      training participants, these differences were significant in unadjusted models.
      CONCLUSION: Our findings suggest that QI training for public health agency
      employees should include both didactic training on QI content and opportunities
      for QI application. Future research should examine if this approach can
      effectively increase successful participation in QI projects for staff in LHDs of
      all sizes.

PMID- 22139320
TI  - Legal frameworks supporting public health department accreditation: lessons
      learned from 10 states.
AB  - CONTEXT: The existence of different types of accreditation legal frameworks,
      embedded in complex and varying state legal infrastructures and political
      environments, raises important legal implications for the national voluntary
      accreditation program. OBJECTIVE: To increase an understanding of accreditation
      enabling laws nationwide. DESIGN: In 2010 to 2011, the North Carolina Institute
      for Public Health conducted a study of state legal frameworks supporting public
      health department accreditation or related programs (ie,
      certification/assessment, performance management, and quality improvement).
      First, a mapping study was conducted to identify current programs and their legal
      frameworks. Ten states were then selected for in-depth qualitative case study.
      Data were gathered through semistructured interviews with public health
      practitioners and key stakeholders. RESULTS: The findings from the mapping study
      delineate the accreditation, certification/assessment, performance management, or
      quality improvement program currently in place and the type of legal framework
      supporting it. The citations for statutes and regulations are also included.
      Among the 18 states in the sample, 4 have accreditation programs, 6 have
      certification/assessment programs, and 8 have performance management/quality
      improvement programs. Accreditation programs were most likely to have a statutory
      basis, while performance management and quality improvement programs were most
      often supported via health department policy. The findings from the case study
      provide greater detail about each state, reflecting public health structures,
      programs, legal frameworks, approaches to Public Health Accreditation Board
      (PHAB) accreditation, and legal strategies for achieving accreditation.
      CONCLUSIONS: Early adopter states have pursued a variety of legal frameworks to
      develop their accreditation, certification/assessment, performance management,
      and quality improvement programs. With the voluntary national accreditation
      program scheduled to go live in late 2011, these 10 states have also carefully
      considered options for aligning their activities with PHAB accreditation. Lessons
      derived from this examination can inform public health practitioners, advocates,
      and elected officials about how to best structure legal frameworks to support
      accreditation and related activities.

PMID- 22139322
TI  - Precision of continuous neonatal ventilator respiratory mechanics is improved
      with selected optimal respiratory cycles.
AB  - Given their high apparent variability, bedside continuous respiratory mechanics
      (RM) parameters [excepting tidal volume (V (T))] remain infrequently used for
      adjustment of neonatal ventilatory settings. RM parameters provided by ventilator
      (VRC) from ten recordings of newborns [10 min in synchronised intermittent
      mandatory ventilation and 10 min in assist/control (A/C)] were compared to those
      computed from visually selected assisted leak-free optimal respiratory cycles
      (SRC). Mean values, variability and ability to distinguish patients were compared
      between VRC and SRC. Dynamic resistances were more correlated (r(2) = 0.95) than
      compliances (r (2) = 0.42). V (T)s were correlated only in A/C (r(2) = 0.78).
      C20/C was significantly higher in VRC (1.81 +/- 0.67) than in SRC (1.23 +/- 0.36)
      and frequently out of neonatal reference range. In A/C ventilation, V(T) was
      higher in VRC (5.6 +/- 1.8 ml/kg) than in SRC (4.8 +/- 1.0 ml/kg) (p < 0.05).
      Displayed V (T)s do not reflect those found in optimal assisted breaths and
      therefore have incomplete value in assessing adequacy of ventilator settings. The
      variability of RM parameters provided by the ventilator is large, and
      coefficients of variation were significantly lower with optimal respiratory
      cycles (for resistance, compliance, V (T) and C20/C; 27%, 26%, 18%, 24% in SRC
      and 36%, 35%, 40% and 33% in VRC). Selecting optimal cycles yields RM with two to
      three times higher discriminating power between patients. CONCLUSION: Current
      ventilator's RM parameters have limited clinical use. Using optimal breaths to
      calculate RM parameters improves precision and discriminating power. For
      integration to ventilatory care, automation of this selection must be implemented
      first.

PMID- 22139327
TI  - Changing pattern of intestinal obstruction in northern Jordan.
AB  - BACKGROUND: Obstructed abdominal wall hernias have been reported to be the
      leading cause of mechanical intestinal obstruction (MIO) among adults in
      developing countries. In the developed countries, postoperative adhesions are the
      commonest cause. With the worldwide improvements in health services and
      education, especially in developing countries, we aimed to determine the effects
      of these improvements on the patterns and outcomes of management of MIO in Jordan
      METHODS: The records of all patients who were treated for MIO between the years
      2005 and 2010 were reviewed retrospectively. Causes of MIO, presenting symptoms,
      the main imaging study performed, and the results of management are described.
      The pattern was compared with that in a previous 1993 report from Jordan.
      RESULTS: A total of 88 patients were treated for MIO. Postoperative adhesions in
      52.5%, gastrointestinal tumors in 21.0%, and obstructed abdominal wall hernias in
      9.5% were the three major causes of MIO. Three patients developed surgical-site
      infections (3.3%), and one developed a minor anastomotic leak that was treated
      accordingly (1.1%). There were no mortalities. In 1993, obstructed hernias
      accounted for 30% of the MIOs followed by postoperative adhesions and tumors (27
      and 14%, respectively). There was a 7% mortality rate. CONCLUSIONS: Our data
      confirmed that improved health education programs and services changed the
      pattern of causes improved the outcomes of management of MIO in Jordan.

PMID- 22139321
TI  - Effects of lower concentration thrombin on high-mobility group box 1 protein
      mediated inflammatory responses.
AB  - As a late mediator of inflammation, the high-mobility group box 1 protein (HMGB1)
      plays a key role in the inflammatory responses to tissue injury and infection by
      inducing and extending the production of proinflammatory cytokines. It has been
      observed that lower concentration thrombin mediates anti-inflammatory activities.
      The aim of this study was to investigate whether lower concentration thrombin
      could modulate HMGB1 expression and could inhibit HMGB1-mediated inflammatory
      responses in human umbilical vein endothelial cells (HUVECs). Here, results
      showed that lower concentration thrombin or thrombin receptor agonist peptide
      inhibits lipopolysaccharide-induced HMGB1 release from HUVECs. And lower
      concentration thrombin has inhibitory effects not only on the expression of cell
      adhesion molecules but also on neutrophils adhesion and migration toward HUVECs
      in response to HMGB1. Interestingly, the HMGB1-induced nuclear factor kappa B
      activation and tumor necrosis factor-alpha release from HUVECs were inhibited by
      lower concentration thrombin. Given these results, lower concentration thrombin
      could be a strong candidate as a therapeutic agent for various systemic
      inflammatory diseases.

PMID- 22139330
TI  - Comparative soil metal analyses in Sudbury (Ontario, Canada) and Lubumbashi
      (Katanga, DR-Congo).
AB  - DR-Congo is a main world producer of copper (Cu) and cobalt (Co). Several
      hydrometallurgical plants and smelters also produced zinc, arsenic, and cadmium
      as by-products. In Sudbury (Canada), the production of nickel, copper and other
      metals has been maintained at high levels while industrial SO(2) emissions have
      been reduced by approximately 90% through combination of industrial technological
      developments and legislated controls. Metal analysis in the present study
      revealed that the levels of copper and cobalt in soils from mining sites in the
      Lubumbashi (DR-Congo) were up to 200 fold higher compared to contaminated Sudbury
      sites and tailings. Zinc content in soil samples from some mining areas in
      Lubumbashi was at least 70 times higher compared to samples from the Sudbury
      area. Nickel content in soil samples from Lubumbashi were much lower compared to
      the Sudbury Region samples. Overall, this study confirms that the African Copper
      belt region is among the ten most polluted areas in the world.

PMID- 22139329
TI  - MYC family amplification and clinical risk-factors interact to predict an
      extremely poor prognosis in childhood medulloblastoma.
AB  - The MYC oncogenes are the most commonly amplified loci in medulloblastoma, and
      have previously been proposed as biomarkers of adverse disease prognosis by us
      and others. Here, we report focussed and comprehensive investigations of MYCC,
      MYCN and MYCL in an extensive medulloblastoma cohort (n = 292), aimed to define
      more precisely their biological significance and optimal clinical application to
      direct improved disease risk-stratification and individualisation of therapy.
      MYCC and MYCN expression elevations were multifactorial, associated with high
      risk (gene amplification, large-cell/anaplastic pathology (LCA)) and favourable
      risk (WNT/SHH molecular subgroups) disease features. Highly variable cellular
      gene amplification patterns underlay overall MYC copy number elevations observed
      in tumour biopsies; we used these alternative measures together to define
      quantitative methodologies and thresholds for amplification detection in
      routinely collected tumour material. MYCC and MYCN amplification, but not gain,
      each had independent prognostic significance in non-infants (>=3.0-16.0 years),
      but MYCC conferred a greater hazard to survival than MYCN when considered across
      this treatment group. MYCN's weaker group-wide survival relationship may be
      explained by its pleiotropic behaviour between clinical disease-risk groups; MYCN
      predicted poor prognosis in clinical high-risk (metastatic (M+) or LCA), but not
      standard-risk, patients. Extending these findings, survival decreased in
      proportion to the total number of independently significant high-risk features
      present (LCA, M+ or MYCC/MYCN amplification). This cumulative-risk model defines
      a patient group characterised by >=2 independent risk-factors and an extremely
      poor prognosis (<15% survival), which can be identified straightforwardly using
      the reported MYC amplification detection methodologies alongside clinical
      assessments, enabling targeting for novel/intensified therapies in future
      clinical studies.

PMID- 22139323
TI  - Involvement of immunologic and biochemical mechanisms in the pathogenesis of
      Tourette's syndrome.
AB  - Tourette's syndrome is a neurodevelopmental disorder clinically characterized by
      multiple motor and phonic tics. It is likely that a neurobiological
      susceptibility to the disorder is established during development by the
      interaction of genetic, biochemical, immunological, and environmental factors.
      This study sought to investigate the possible correlation of several
      immunological and biochemical markers with Tourette's syndrome. Children with
      Tourette's syndrome attending a tertiary pediatric medical center from May 2008
      to April 2010, and healthy age-matched control subjects underwent a comprehensive
      biochemical and immunological work-up. Demographic data were abstracted from the
      medical records. Findings were compared between the groups and analyzed
      statistically. Sixty-eight children with Tourette's syndrome (58 males, 85.3%)
      and 36 healthy children (25 males, 69.4%) were recruited. Compared with the
      control group, the Tourette's syndrome group had significantly higher levels of
      ferritin (p = 0.01) and hemoglobin (p = 0.02), a lower level of zinc (p = 0.05),
      and a lower percentage of non-ceruloplasmin copper (p = 0.01). Analysis of the
      immunological markers revealed no significant between-group differences in IgA,
      IgM or IgG; however, IgE and IgG-4 levels were significantly higher in the
      Tourette's syndrome group (p = 0.04 and p = 0.02, respectively). Children with
      Tourette's syndrome have high levels of biochemical indices of oxidative stress
      and the quantitative immunoglobulins. These findings add to the still-limited
      knowledge on the pathogenesis of Tourette's syndrome and may have implications
      for the development of novel therapeutic modalities.

PMID- 22139331
TI  - Analysis of diazinon agricultural use in regions of frequent surface water
      detections in California, USA.
AB  - For five agricultural regions in California, USA, detection frequency of diazinon
      in surface water and several aspects of its use were determined from recent data
      (2005-2010): application method, product formulation and primary crops. Diazinon
      detection frequencies ranged from 10% to 91%. Application method and product
      formulations used were similar in all regions. The primary crops treated varied
      from lettuce (77%) in the regions with highest detections frequencies to tree
      crops (53%) in those with the lowest. The results suggest that the variation in
      diazinon detection frequencies likely was not due to the application method or
      formulation type.

PMID- 22139333
TI  - Estrogens: new players in spermatogenesis.
AB  - Aromatase that irreversibly transforms androgens into estrogens is present in the
      smooth endoplasmic reticulum of nearly all cell types in the mammalian testis. In
      rodents, all testicular cells except for myoid cells express aromatase activity.
      We have demonstrated the presence of the functional aromatase (transcript or
      protein, and biological activity) in adult rat germ cells including pachytene
      spermatocytes and round spermatids. We have also demonstrated estrogen output
      from these cells equivalent to that of Leydig cells. Unlike androgen receptors,
      which are localized mainly in testicular somatic cells, estrogen receptors are
      present in both somatic and germ cells in the testis. Moreover, we have recently
      described the rapid membrane effects of estrogens (via G protein-coupled receptor
      [GPER]) in purified rat germ cells. On the basis of various experimental models,
      in vitro studies and clinical data, it can be concluded that estrogens play an
      essential role in male reproduction, specifically in the development of
      spermatozoa.

PMID- 22139332
TI  - Arsenic-induced straighthead: an impending threat to sustainable rice production
      in South and South-East Asia!
AB  - Straighthead is a physiological disorder of rice (Oryza sativa L.) that results
      in sterile florets with distorted lemma and palea, and the panicles or heads may
      not form at all in extreme cases. Heads remain upright at maturity, hence the
      name 'straighthead'. The diseased panicles may not emerge from the flag leaf
      sheath when the disease is severe. Straighthead disease in rice results in poorly
      developed panicles and significant yield loss. Although other soil
      physicochemical factors involved, arsenic contamination in soil has also been
      reported to be closely associated with straighthead of rice. Monosodium
      methanearsonate has been a popular herbicide in cotton production in the USA,
      which has shown to cause injuries in rice that are similar to straighthead. Since
      toxicity of inorganic arsenic (iAs) is higher than other forms of arsenic, it may
      produce a more severe straighthead disorder in rice. The use of iAs-rich
      groundwater for irrigation, and the increase of iAs concentrations in
      agricultural soil in arsenic epidemic South and South-East Asia may cause a high
      incidence of straighthead in rice, resulting in a threat to sustainable rice
      production in this region.

PMID- 22139334
TI  - A new classification of a preovulatory oocyte maturation stage suitable for the
      synchronization of ovulation in controlled reproduction of Eurasian perch Perca
      fluviatilis L.
AB  - To improve controlled reproduction of Eurasian perch Perca fluviatilis, the
      criteria for the evaluation of final oocyte maturation stages were revised. The
      new classification covers six preovulatory maturational stages (I -VI) from the
      end of vitellogenesis to germinal vesicle breakdown (GVBD) and was based on
      macroscopic changes of preovulatory oocytes (position of the germinal vesicle,
      GVBD, oil droplets coalescence). The observation was performed during out-of
      season artificial reproduction with the use of a single hCG injection (500
      IU/kg). The classification was subsequently verified with the controlled
      reproduction of wild female perch with the use of hormonal stimulation (500 IU
      hCG/kg of body weight at 12 degrees C). The females were at different
      maturational stages and constituted respective experimental groups (I-VI). During
      the experiment, ovulation appeared to be considerably synchronized within
      particular groups. Statistical differences in latency time (time between hormonal
      treatment and ovulation) were found between experimental groups (mean latency
      time: 110, 92, 68, 49, 29 and 18 h in groups representing VI, V, IV, III, II and
      I stage of the proposed classification, respectively). The proposed
      classification and the results presented in the study allowed for effective
      synchronisation of ovulation. The use of our new oocyte maturation classification
      may positively influence the effectiveness of Eurasian perch production.

PMID- 22139325
TI  - Compensatory brain activation in children with attention deficit/hyperactivity
      disorder during a simplified Go/No-go task.
AB  - Given that a number of recent studies have shown attenuated brain activation in
      prefrontal regions in children with ADHD, it has been recognized as a disorder in
      executive function. However, fewer studies have focused exclusively on the
      compensatory brain activation in ADHD. The present study objective was to
      investigate the compensatory brain activation patterns during response inhibition
      (RI) processing in ADHD children. In this study, 15 ADHD children and 15 sex-,
      age-, and IQ-matched control children were scanned with a 3-T MRI equipment while
      performing a simplified letter Go/No-go task. The results showed more brain
      activation in the ADHD group compared with the control group, whereas the
      accuracy and reaction time of behavioral performance were the same. Children with
      ADHD did not activate the normal RI brain circuits, which are thought to be
      predominantly located in the right middle/inferior frontal gyrus (BA46/44), right
      inferior parietal regions (BA40), and pre-SMA(BA6), but instead, activated brain
      regions, such as the left inferior frontal cortex, the right inferior temporal
      cortex, the right precentral gyrus, the left postcentral gyrus, the inferior
      occipital cortex, the middle occipital cortex, the right calcarine, the right
      hippocampus, the right midbrain, and the cerebellum. Our conclusion is that
      children with ADHD tend to compensatorily use more posterior and diffusive brain
      regions to sustain normal RI function.

PMID- 22139339
TI  - The use of latex beads in external quality assurance and internal quality control
      for routine semen analysis.
AB  - The usefulness of latex beads of defined concentration was assessed as a
      substitute for sperm in the performance of External Quality Assurance (EQA) and
      Internal Quality Control (IQC) of semen analysis. Within the EQA programme,
      mean+/-SEM bias (%) was significantly reduced in 2007 compared to 2002 for both
      specialist (6.0%+/-5.4% vs. 55.0%+/-5.9%) and non-specialist (18.4%+/-5.9% vs.
      90.9%+/-13.4%) laboratories (both p<0.0001), indicating improved accuracy over
      time. Within the IQC programme, the beads were used in the appraisal of two
      scientists, one experienced and one inexperienced, against a known standard.
      Beads were also used to calibrate eleven counting chambers, resulting in one old
      chamber being discarded due to its poor performance. The present study has shown
      that the use of a defined concentration of beads is an excellent adjunct to IQC
      and EQA programmes enabling the performance of both people and equipment to be
      assessed in an objective manner.

PMID- 22139338
TI  - Semen quality parameters and embryo lethality in mice deficient for Trp53
      protein.
AB  - Trp53 is a protein which is able to control semen parameters in mice, but the
      extent of that control depends on the genetic background of the mouse strain.
      Males from C57BL/6Kw, 129/Sv, C57BL*129 -p53+/+ (wild type controls) and
      C57BL*129-p53-/- (mutants) strains were used in the study, and histology and
      light microscopy were applied to evaluate the influence of genetic background and
      Trp53 (p53) genotype on testes morphology and semen quality in male mice. We
      showed that sperm head morphology, maturity and tail membrane integrity were
      controlled only by the genetic background of C57BL/6Kw and 129/Sv males, while
      testes weight and sperm concentration depended on both the genetic background and
      p53 genotype. Cell accumulation in seminiferous tubules may be responsible for
      heavier testes of p53-deficient males. In addition, to examine the effect of sex
      and p53 genotype on embryo lethality, pairs of control (C57BL*129-p53+/+) and
      heterozygous (C57BL*129-p53+/-) mice were examined. Before day 7 post coitum
      (dpc), female and male embryos were equally resorbed in both crosses types. After
      7 dpc, preferential female embryo lethality in the heterozygote pairs was
      responsible for the skewed sex ratio in their progeny. Also, mutant female and
      male newborns were underrepresented in the litters of the heterozygous breeding
      pairs.

PMID- 22139335
TI  - Expression of aquaporin 1 in the pig peri-ovarian vascular complex during the
      estrous cycle and early pregnancy.
AB  - Aquaporin 1 (AQP1) is a water channel protein expressed in endothelial and
      epithelial cells of many tissues, including the vasculature, where it serves to
      increase water permeability of the cell membrane. The aim of this study was to
      investigate the expression and distribution of AQP1 in porcine peri-ovarian
      vascular complex (PVC) during the estrous cycle and early pregnancy.
      Immunohistochemistry and semi-quantitative immunoblotting techniques were used.
      We have demonstrated the presence of AQP1 protein in the endothelial cells of the
      lymphatic and vascular endothelium of the PVC during the pig estrous cycle and
      early pregnancy. The expression of AQP1 protein in the PVC did not change
      significantly between Days 10-12 and 14-16, but increased on Days 2-4 and 18-20
      when compared with Days 10-12 and 14-16 of the estrous cycle. In pregnant gilts,
      the expression of AQP1 did not differ significantly during the onset and the end
      of the implantation process and also when compared to the mid- and late-luteal
      phases of the estrous cycle. In conclusion, AQP1 is expressed in the endothelial
      cells of PVC and may modulate hormonal regulation of reproductive organs.

PMID- 22139336
TI  - Low incidence of chromosome aberrations in spermatozoa of fertile boars.
AB  - Chromosomal imbalance in gametes and embryos is one of the factors contributing
      to early embryonic mortality. Although the rate of chromosomally abnormal sperm
      cells is low and usually does not exceed 1%, there is no clear indication of
      fertilizing potential of such gametes. The aim of the experiment was to
      investigate the type and incidence of numerical chromosomal aberrations in
      spermatozoa produced by fertile boars used in artificial insemination (AI). We
      used the protocol of fluorescent in situ hybridization (FISH) on sperm interphase
      nuclei with molecular probes for porcine chromosome pairs 1 and 10. Altogether 12
      348 sperm cells were examined. Disomy was observed in spermatozoa of all seven AI
      boars whereas only one diploid cell was identified in all screened sperm cells.
      The average rate of chromosomally unbalanced sperm was 0.105% (13/12 348) with an
      inter-individual variation from 0.048% to 0.194%. Among abnormal sperm cells,
      both disomy (0.097%) and diploidy (0.008%) were detected. Nullisomy was not
      included into calculations. The estimated aneuploidy rate calculated by doubling
      the number of disomic cells was 0.194%. Chromosome pair 10 was significantly more
      often involved in non-disjunction (75%, 9/12 aneuploid sperm cells) than
      chromosome pair 1 (25%, 3/12). We have shown for the pig that the rate of disomic
      cells falls into a range presented by other authors, whereas that of diploid
      spermatozoa appeared to be lower in the present study. In conclusion, numerical
      chromosome aberrations were present in spermatozoa of all AI boars analyzed in
      this study. Therefore, it can be assumed that the presence of unbalanced
      spermatozoa at the level observed in fertile males does not significantly affect
      their reproductive potential.

PMID- 22139324
TI  - The role of the kynurenine metabolism in major depression.
AB  - There are circumferential evidences that major depression is associated with mild
      pro-inflammatory state. Both physiological and psychological stress can induce
      increased production of pro-inflammatory mediators, reactive oxygen species (ROS)
      and hypothalamo-hypophyseal-adrenal axis disturbances. While both pro
      inflammatory mediators and ROS could activate the tryptophan breakdown and
      kynurenine pathway with a shift toward the neurotoxic arm, chronic
      hypercortisolism could also enhance tryptophan breakdown and induce
      neurodegenerative changes. The imbalanced kynurenine metabolism in terms of
      neuroprotective and neurotoxic effects was demonstrated in major depression, and
      in drug-induced neuropsychiatric side effects, such as interferon-treated
      depression. The changes in periphery are shown to be associated with central
      changes. Those changes might be partly contributed by genetic factors. While some
      of the currently available antidepressants could reverse the pro-inflammatory
      state of the depressed patients, these medications could not efficiently improve
      those metabolic and neurochemical changes within the period that could induce
      clinical improvement. In this review, the role of kynurenine metabolism which
      interacts with other neurochemicals is discussed as a major contributing
      pathophysiological mechanism in major depression. Moreover, the future
      therapeutic opportunities are also discussed in this review.

PMID- 22139337
TI  - Long-term betacarotene-supplementation enhances serum insulin concentrations 
      without effect on the onset of puberty in the female goat.
AB  - The effect of betacarotene (BC) supplementation on the onset of puberty and serum
      insulin levels in goats was evaluated in the study. In June, prepuberal goats
      (n=17; 3 months old; 7/8 Saanen-Alpine; 26 degrees  NL) were randomly assigned to
      one of two groups: 1/ betacarotene group supplemented daily with 50 mg of BC
      (n=9; live weight [LW]: 17.3+/-1.0 kg; body condition score [BCS]: 3.34+/-0.12)
      or 2/ control group (CONT; n=8; LW:16.1+/-1.0 kg; BCS=3.17+/-0.12). From June to
      November, an intermittent blood sampling was performed twice per week in both
      groups to evaluate serum progesterone (P(4)), while monthly samples were intended
      for insulin (INS) determination. Initial mean LW (16.7+/-1.0 kg) and BCS (3.31+/
      0.12) were similar (p>0.05) in both groups. Mean serum insulin (1.37 vs. 1.18+/
      0.09 ng/ml), age of puberty (215.7 vs. 226.5+/-6.6 days) and the percentage of
      goats reaching puberty (44.4 vs. 25.0+/-17.0%) did not differ (p>0.05) between BC
      and CONT group, respectively. However, increase in serum insulin during the
      second half of the experiment was observed in BC group (p<0.05) which was
      positively correlated with LW (r=0.95; p<0.05). In addition, as LW (r=-0.89) and
      serum insulin (r=-0.76) levels increased, the natural photoperiod decreased,
      revealing negative correlations (p<0.05) between the respective variables. In
      this study, BC supplementation did not promote precocious puberty and did not
      affect the percentage of goats reaching activation of the hypothalamic
      hypophyseal-gonadal axis during the establishment of puberty. Nonetheless, BC
      supplementation positively affected the release pattern of insulin suggesting a
      potential role of BC as pancreas-activating molecule.

PMID- 22139341
TI  - Estimation of instantaneous secretory rates and intrinsic characteristics of
      luteinizing hormone secretion in women with Kallmann syndrome before and after
      estriol administration.
AB  - Three Kallmann syndrome (KS) patients were examined to assess characteristics of
      LH response to GnRH bolus, with and without GnRH sensitization using
      Instantaneous Secretory Rate (ISR) computation before and after estriol treatment
      (60 days, 2 mg/day). Six healthy women were enrolled as controls and underwent
      GnRH bolus during the early follicular phase (days 3-5 of the menstrual cycle).
      After estriol treatment, the KS patients showed a higher LH response to GnRH
      bolus and similar LH pulse duration to healthy controls. These data support the
      hypothesis that the administration of weak estrogen improves LH response to GnRH
      in hypogonadotropic women with KS.

PMID- 22139342
TI  - Correlation of E-cadherin and CD44v6 expression with clinical pathology in
      esophageal carcinoma.
AB  - Cell adhesion, important for maintaining tissue architecture, plays a role in
      numerous cancers and particularly in tumor progression. In the present study, we
      investigated perturbations in the expression of two important adhesion proteins,
      epithelial (E)-cadherin and CD44v6, in esophageal carcinoma (EC). EC specimens
      were obtained from 42 patients undergoing resection of EC; both cancer and
      adjacent normal tissue were collected. Expression of E-cadherin and CD44v6 was
      detected by immunohistochemistry and the correlation between the expression of
      these two proteins and their individual relationships with pathology were
      determined. E-cadherin expression in EC tissue was significantly less common than
      in adjacent normal tissue. Furthermore, absence of E-cadherin expression was
      correlated with infiltration depth, lymph node metastasis, distant metastases and
      TNM stage (P<0.05), but not with gender, age, differentiation or tumor size. By
      contrast, CD44v6 expression in EC was significantly higher than that in adjacent
      normal tissue and was correlated with differentiation, distant metastases and TNM
      stage (P<0.05), but not with other clinicopathological parameters. Additionally,
      we observed a negative correlation between E-cadherin and CD44v6 expression in EC
      (P<0.05). Based on their correlations with pathology, we suggest that the
      expression of E-cadherin and CD44v6 is important roles in promoting the
      infiltration and metastasis of EC.

PMID- 22139340
TI  - Levels of heat shock protein transcripts in normal follicles and ovarian
      follicular cysts.
AB  - In the study, the gene expression of several heat shock proteins (HSPs) was
      determined in normal follicles and cystic follicles from cattle. A lower
      expression of HSP10 and HSP40 was observed in granulosa and theca cells of cysts
      compared to normal follicles. HSP27 was significantly less expressed in granulosa
      cells in cystic and large antral follicles than in other follicular categories.
      HSP60 and HSP90a expressions were highest in theca cells of cysts. However, HSP70
      and HSP90b exhibited a lower expression in cysts than in healthy follicles.

PMID- 22139344
TI  - Structures and energetics of electrosprayed uracil(n)Ca2+ clusters (n = 14-4) in
      the gas phase.
AB  - Clusters of uracil (U) about a calcium dication, U(n)Ca(2+) (n = 14-4), have been
      studied in the gas phase by both experimental and theoretical methods.
      Temperature dependent blackbody infrared radiative dissociation (BIRD)
      experiments were performed on U(n)Ca(2+) clusters with n = 14-5 and the observed
      Arrhenius parameters are reported here. Master equation modeling of the BIRD
      kinetics data was carried out to determine threshold dissociation energies.
      Initial geometry calculations were performed using the B3LYP density functional
      and 3-21G(d) basis set. A sample of ten conformations per cluster was obtained
      through a simulated annealing study. These structures were optimized using
      B3LYP/6-31G(d) level of theory. Fragment-based hybrid many body interaction
      (HMBI) MP2/6-311++G(2df,2p)/Amoeba calculations were performed on representative
      conformations to determine theoretical binding energies. Results were examined in
      relation to cluster size (n). A significant increase in the energy required to
      remove uracil from U(6)Ca(2+) when compared to larger clusters supports previous
      reports that the calcium ion is coordinated by six uracil molecules in the
      formation of an inner shell. For clusters larger than n = 6, an odd-even
      alternation in threshold dissociation energies was observed, suggesting that the
      outer shell uracil molecules bind as dimers to the inner core. Proposed binding
      schemes are presented. Multiple structures of U(5)Ca(2+) are suggested as being
      present in the gas phase where the fifth uracil may be either part of the first
      or second solvation shell.

PMID- 22139343
TI  - Exposure to heavy metals in blood and risk perception of the population living in
      the vicinity of municipal waste incinerators in Korea.
AB  - BACKGROUND, AIM, AND SCOPE: The purpose of this study was to monitor and present
      the heavy metal concentrations in the blood of residents of areas near municipal
      waste incinerators (MWIs), who are more prone to environmental pollution. We also
      sought to compare and analyze the residents' perception of environmental
      pollution as one of the factors affecting heavy metal concentrations in the blood
      using a survey about the perceived damage caused by the facilities. Since heavy
      metal levels in the blood can be affected not only by local environmental
      pollution but also by personal and occupational factors, heavy metal levels in
      the blood need to be verified and consistently monitored. METHODS: Residents who
      live within 300 m of MWIs in Seoul are acknowledged to be under indirect
      influence according to the Waste Disposal Act. A survey was given to 841
      residents living within 300 m of a MWI from 2006 to 2009. The concentrations of
      heavy metals (lead, cadmium, and mercury) in the blood were measured in the 841
      surveyed residents and in 105 residents in reference areas. Additionally, the
      perception of the damage caused by municipal waste incinerators was investigated
      using scores from 1 to 5 on a Likert scale. RESULTS: The measurements of the
      heavy metal concentrations in the blood showed that the mean concentrations of
      lead, cadmium, and mercury were 43.1, 1.7, and 1.3 ug/L, respectively. The blood
      levels of lead and cadmium were slightly higher in the group of the subjects who
      had resided the longest near the municipal waste incinerators. When compared with
      the domestic investigation by the Ministry of Environment, the concentrations of
      lead and cadmium were a little higher, while that of mercury was a little lower.
      Overall, there was no significant difference in the distribution of heavy metal
      levels in the blood among age groups. Additionally, the investigation of the
      perceived damage from municipal waste incinerators showed that the subjects.

PMID- 22139345
TI  - Engineered glucose isomerase from Streptomyces sp. SK is resistant to Ca2+
      inhibition and Co2+ independent.
AB  - The role of two amino acid residues linked to the two catalytic histidines His54
      and His220 in kinetics and physicochemical properties of the Streptomyces sp. SK
      glucose isomerase (SKGI) was investigated by site-directed mutagenesis and
      molecular modeling. Two single mutations, F53L and G219D, and a double mutation
      F53L/G219D was introduced into the xylA SKGI gene. The F53L mutation increases
      the thermostability and the catalytic efficiency and also slightly shifts the
      optimum pH from 6.5 to 7, but displays a profile being similar to that of the
      wild-type enzyme concerning the effect of various metal ions. The G219D mutant is
      resistant to calcium inhibition retaining about 80% of its residual activity in
      10 mM Ca2+ instead of 10% for the wild-type. This variant is activated by Mn2+
      ions, but not Co2+, as seen for the wild-type enzyme. It does not require the
      latter for its thermostability, but has its half-life time displaced from 50 to
      20 min at 85 degrees C. The double mutation F53L/G219D restores the
      thermostability as seen for the wild-type enzyme while maintaining the resistance
      to the calcium inhibition. Molecular modeling suggests that the increase in
      thermostability is due to new hydrophobic interactions stabilizing alpha2 helix
      and that the resistance to calcium inhibition is a result of narrowing the
      binding site of catalytic ion.

PMID- 22139350
TI  - Intraoperative clouding of a posterior chamber intraocular lens.
AB  - The glistening and delayed opacification of intraocular lenses (IOLs) has been
      reported in literature as a late and permanent change in the acrylic IOL due to
      temperature change. We report a case in which clouding and opacification of an
      IOL occurred intraoperatively within a few seconds of implantation into the
      capsular bag after routine phacoemulsification. This phenomenon occurred due to
      the sudden change in temperature of a very cold IOL being implanted into the eye
      at body temperature. The opaqueness lasted for about 3 h then cleared without any
      residual or permanent change to the IOL. This case highlights the effect of
      environmental factors on hydrophillic acrylic IOLs. It is particularly important
      in cold countries and during the winter months. It also reinforces the practice
      of storing the IOL at a correct temperature to avoid sudden fluctuations in its
      surrounding environment.

PMID- 22139348
TI  - Exocytosis of SH-SY5Y single cell with different shapes cultured on ITO micro
      pore electrode.
AB  - Communication between cells by release of specific chemical messengers via
      exocytosis plays crucial roles in biological process. Catecholamines, like
      dopamine, epinephrine, and norepinephrine, which are types of neurotransmitters
      released from cells, can be oxidized and detected by the microelectrodes, and
      amperometric detection of exocytosis is an effective method for studying the
      communication between cells. The experimental results depend on many factors,
      among which the property of the microelectrode, cell states, and their positions
      to each other are particularly important. A type of indium tin oxide (ITO) micro
      pore electrodes, which is characterized by its stability, has been developed with
      photolithography. SH-SY5Y cells can adhere and spread on ITO micro-pore
      electrodes. Therefore, it is possible to investigate the correlation between cell
      morphology and exocytosis. The results show that cells with clear process have
      higher release frequency of norepinephrine compared with cells in spherical
      shape. Combined with fluorescence observation, this technique provides a simple
      and convenient methodology for cell study.

PMID- 22139352
TI  - Idiopathic dendriform pulmonary ossification.
AB  - Diffuse dendriform pulmonary ossification is a rare disorder characterized by
      widespread pulmonary ossification distributed in a characteristic branching
      pattern. It is usually associated with chronic interstitial inflammation and
      fibrosis but may occasionally be idiopathic. The underlying pathogenesis remains
      uncertain. Computed tomography findings characteristically show fine branching
      heterotopic bone formation within the lungs, often in a lower lobe distribution.
      A case of idiopathic dendriform ossification is described in a 34-year-old man
      who presented for investigation of hemoptysis.

PMID- 22139347
TI  - Human endothelial progenitor cells isolated from COPD patients are dysfunctional.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in
      patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).
      More than 44% of these patients present with generalized atherosclerosis at
      autopsy. It is accepted that endothelial progenitor cells (EPCs) participate in
      the repair of dysfunctional endothelium and thus protects against
      atherosclerosis. However, whether COPD affects the repairing capacity of EPCs is
      unknown. Therefore, the objective of this study was to determine whether and how
      EPCs are involved in the vascular repair process in patients with COPD. In our
      study, EPCs from 25 COPD and 16 control patients were isolated by Ficoll density
      gradient centrifugation and identified using fluorescence activated cell sorting.
      Transwell Migratory Assay was performed to determine the number of EPC colony
      forming units and the adherent capacity late-EPCs to human umbilical vein
      endothelial cells. Following arterial damage in NOD/SCID mice, the number of EPCs
      incorporated at the injured vascular site was determined using a fluorescence
      microscope. We found that the number of EPC clusters and cell migration, as well
      as the expression of CXCR4, was significantly decreased in patients with COPD.
      Additionally, the number of late-EPCs adherent to HUVEC tubules was significantly
      reduced, and fewer VEGFR2(+)-staining cells were incorporated into the injured
      site in COPD patients. Our study demonstrates that EPC capacity of repair was
      affected in COPD patients, which may contribute to altered vascular endothelium
      in this patient population.

PMID- 22139349
TI  - Oral tongue cancer patients show a better overall survival than base of tongue
      cancer patients.
AB  - PURPOSE: The purpose of this study was to compare the prognosis of oral tongue
      cancer patients and base of tongue cancer patients. METHODS: One hundred oral
      tongue cancer patients (group A) were matched with 50 base of tongue cancer
      patients (group B) for gender, age, T-stage, and tumor differentiation in this
      study. Survival rate was performed using the Kaplan-Meier analysis, and
      multivariate analysis was conducted using the Logistic regression model. RESULTS:
      There was difference in the survival rate between the two groups. Three- and 5
      year OS (overall survival) of the two groups were 65.0, 51.0% for group A and
      40.0, 28.0% for group B, respectively. For the two groups, 3- and 5-year DSS
      (disease-specific survival) were 61.0, 46.0% for group A and 38.0, 26.0% for
      group B, respectively. Multivariate analysis showed that recurrence (P = 0.019)
      and regional lymph node metastasis (P = 0.043) were significant between the group
      A and group B patients. CONCLUSION: The oral tongue cancer patients had a better
      prognosis than base of tongue cancer patients. The difference in prognosis
      between the oral tongue cancer and the base of tongue cancer patients in this
      study was closely associated with the recurrence and regional lymph node
      metastasis. We conclude that the individual treatment should be used for base of
      tongue cancer patients.

PMID- 22139351
TI  - Herpetic keratitis after corneal collagen cross-linking with riboflavin and
      ultraviolet-A for progressive keratoconus.
AB  - To describe a case of herpetic keratitis after corneal collagen cross-linking
      (CXL) with riboflavin and ultraviolet-A for progressive keratoconus. A 31-year
      old woman with rapidly progressive keratoconus in the left eye was treated with
      CXL. Four days postoperatively, a dendritic ulcer developed in the treated eye.
      The diagnosis was confirmed with polymerase chain reaction analysis of the
      corneal swab for herpes simplex. The patient had no prior history of herpetic eye
      disease or cold sores. The keratitis resolved in 10 days with treatment. At 1
      month, the visual acuity was stable, but a mild superficial opacity was noted.
      Herpetic keratitis can be induced by CXL even in patients with no history of
      previous herpetic eye disease. Early diagnosis and proper treatment can
      facilitate successful management of this rare but important complication.

PMID- 22139353
TI  - The variability in prognostic values of right ventricular-to-left ventricular
      diameter ratios derived from different measurement methods on computed tomography
      pulmonary angiography: a patient outcome study.
AB  - PURPOSE: To evaluate variability in right ventricular-to-left ventricular (RV/LV)
      diameter ratios introduced by differences in measurement methods and the
      subsequent influence on the accuracy of predicting outcomes for patients with
      acute pulmonary embolism (PE). MATERIALS AND METHODS: For 200 consecutive
      computed tomography pulmonary angiograms positive for acute PE, RV/LV diameter
      ratios were retrospectively measured using 3 different 4-chamber reformations and
      from axial images alone. The first 4-chamber reformation method (4ch-1) was a
      single oblique technique using LV morphology landmarks; the other 2 methods (4ch
      2 and 4ch-3) were double oblique techniques that created an intermediate short
      axis image to identify the maximum RV diameter but with different approaches to
      reach short-axis images. Interobserver variability was measured using 30 cases.
      Receiver-operating characteristic analysis compared the accuracy of predicting
      outcomes among the 4 measurements for PE-related death, and for death or the need
      for intensive therapies (composite outcome). RESULTS: The difference in median
      RV/LV diameter ratios was insignificant among 4ch-2 (1.01), 4ch-3 (1.02), and
      axial (1.03) datasets, whereas that from 4ch-1 (0.93) was significantly lower
      (P<0.001). Correlation between observers was excellent for all 4 datasets
      (r=0.881 to 0.925). Compared with 4ch-1, the other 3 datasets equally achieved
      higher accuracy in predicting PE-related 30-day mortality (area under curve: 0.55
      vs. 0.69 to 0.73, P=0.007 to 0.019) and a composite outcome (area under curve:
      0.65 vs. 0.77 to 0.78, P=0.003 to 0.010). CONCLUSIONS: Double oblique 4-chamber
      reformation methods that use intermediate short-axis images to optimize RV size
      predict outcomes better in patients with acute PE than do single oblique methods
      using only LV landmarks; however, their accuracy is not superior to that from
      measurements based on axial images.

PMID- 22139346
TI  - Vitamin E ameliorates ox-LDL-induced foam cells formation through modulating the
      activities of oxidative stress-induced NF-kappaB pathway.
AB  - The role of antioxidant supplementation with vitamin E in the prevention of
      atherosclerosis has been a topic of considerable recent interest. The relevance
      of vitamin E for macrophage-derived foam cell formation, a hallmark of
      atherosclerosis, however, has not been unequivocally resolved. Here, we
      investigated the effect of oxidized LDL (ox-LDL) and vitamin E on lipid
      accumulation and total cholesterol content in U937 macrophages, reactive oxygen
      species generation and expression of nuclear factor-kappaB (NF-kappaB) signaling
      pathway. The results showed that the mRNA expression and protein levels of P
      selectin were evident in U937 macrophages treated with ox-LDL and vitamin E,
      which indicating that expression of P-selectin is important in macrophage-derived
      foam cell formation. Moreover, P-selectin changes in ox-LDL-induced foam cell
      formation can be mediated by vitamin E through activities of nuclear NF-kappaB
      activated by serine phosphorylation of NF-kappaB inhibitor alpha, suggesting that
      activation of NF-kappaB pathway by macrophages may occur. Taken together, these
      data suggested that vitamin E can prevent ox-LDL-induced foam cell macrophages
      formation through modulating the activities of oxidative stress-induced NF-kappaB
      pathway.

PMID- 22139354
TI  - CD16(+) natural killer cells play a limited role against primary dengue virus
      infection in tamarins.
AB  - CD16 is a major molecule expressed on NK cells. To directly assess the role of
      natural killer (NK) cells in dengue virus (DENV) infection in vivo, CD16 antibody
      treated tamarins were inoculated with a DENV-2 strain. This resulted in the
      transient depletion of CD16(+) NK cells, whereas no significant effects on the
      overall levels or kinetics of plasma viral loads and antiviral antibodies were
      observed in the treated monkeys when compared to control monkeys. It remains
      elusive whether the CD16(-) NK subpopulation could play an important role in the
      control of primary DENV infection.

PMID- 22139355
TI  - Molecular characterization of two recombinant potato virus Y isolates from China.
AB  - Isolates of potato virus Y (PVY) have been divided into several strains. We
      determined the genomic sequences of PVY isolates AQ4 and FZ10 from tobacco in
      China. AQ4 and FZ10 had genome of 9700 and 9698 nucleotides, respectively. In
      phylogenetic analysis of complete genome sequences, AQ4 was clustered with strain
      N-Wi, and FZ10 with NTN. AQ4 had two recombination sites within the P1 and P3
      genes, while FZ10 had three within the P1, P3 and NIa-Pro genes. When compared to
      typical NTN isolates, FZ10 lacked a recombination site within the CP gene and,
      thus, represents a novel recombination type of PVY.

PMID- 22139356
TI  - Structural insights into the neutralization mechanism of a higher primate
      antibody against dengue virus.
AB  - The four serotypes of dengue virus (DENV-1 to -4) cause the most important
      emerging viral disease. Protein E, the principal viral envelope glycoprotein,
      mediates fusion of the viral and endosomal membranes during virus entry and is
      the target of neutralizing antibodies. However, the epitopes of strongly
      neutralizing human antibodies have not been described despite their importance to
      vaccine development. The chimpanzee Mab 5H2 potently neutralizes DENV-4 by
      binding to domain I of E. The crystal structure of Fab 5H2 bound to E from DENV-4
      shows that antibody binding prevents formation of the fusogenic hairpin
      conformation of E, which together with in-vitro assays, demonstrates that 5H2
      neutralizes by blocking membrane fusion in the endosome. Furthermore, we show
      that human sera from patients recovering from DENV-4 infection contain antibodies
      that bind to the 5H2 epitope region on domain I. This study, thus, provides new
      information and tools for effective vaccine design to prevent dengue disease.

PMID- 22139359
TI  - Impact of preoperative percutaneous cardiopulmonary support on outcome following
      left ventricular assist device implantation.
AB  - BACKGROUND: The purpose of the present study was to determine the impact of
      preoperative percutaneous cardiopulmonary support (PCPS) on long-term survival
      following implantation of a left ventricular assist device (LVAD). METHODS AND
      RESULTS: Between 1999 and 2010, we used implantable (n=12) and paracorporeal
      (n=91) LVADs in 103 consecutive cardiomyopathy patients as a bridge to
      transplantation. Prior to LVAD implantation, all patients received inotropes, and
      25 patients (24%) received PCPS because of cardiogenic shock. Postoperatively,
      there were no early mortalities within 30 days after surgery, and patients
      survived on LVAD for 560+/-391 days, of whom 9 patients recovered and 32
      underwent heart transplantation after 711+/-360 days of LVAD support. More
      patients with preoperative PCPS required nitric oxide inhalation and prolonged
      inotropic support to maintain adequate LVAD flow. In addition, bilirubin level at
      1 month after LVAD implantation was significantly higher in patients with
      preoperative PCPS. Cox regression analysis identified preoperative PCPS support
      as the only significant predictor for death after LVAD implantation and overall
      survival was significantly better in patients without preoperative PCPS.
      CONCLUSIONS: Despite adequate hemodynamic support after LVAD implantation,
      patients with preoperative PCPS had significantly worse survival. LVAD should be
      used for patients with end-stage heart failure, before PCPS is required for
      hemodynamic support.

PMID- 22139357
TI  - H2O2 stress-specific regulation of S. pombe MAPK Sty1 by mitochondrial protein
      phosphatase Ptc4.
AB  - In fission yeast, the stress-activated MAP kinase, Sty1, is activated via
      phosphorylation upon exposure to stress and orchestrates an appropriate response.
      Its activity is attenuated by either serine/threonine PP2C or tyrosine
      phosphatases. Here, we found that the PP2C phosphatase, Ptc4, plays an important
      role in inactivating Sty1 specifically upon oxidative stress. Sty1 activity
      remains high in a ptc4 deletion mutant upon H(2)O(2) but not under other types of
      stress. Surprisingly, Ptc4 localizes to the mitochondria and is targeted there by
      an N-terminal mitochondrial targeting sequence (MTS), which is cleaved upon
      import. A fraction of Sty1 also localizes to the mitochondria suggesting that
      Ptc4 attenuates the activity of a mitochondrial pool of this MAPK. Cleavage of
      the Ptc4 MTS is greatly reduced specifically upon H(2)O(2), resulting in the full
      length form of the phosphatase; this displays a stronger interaction with Sty1,
      thus suggesting a novel mechanism by which the negative regulation of MAPK
      signalling is controlled and providing an explanation for the oxidative stress
      specific nature of the regulation of Sty1 by Ptc4.

PMID- 22139360
TI  - Echocardiographic evaluation of the single right ventricle in congenital heart
      disease: results of new techniques.
AB  - Right ventricular (RV) function is increasingly recognized as having prognostic
      significance in various disease processes. The current gold standard for
      noninvasive measurement of RV function is cardiac magnetic resonance imaging;
      however, because of practical considerations, echocardiography remains the most
      often used modality for evaluating the RV. In the past, because of its complex
      morphology, echocardiographic assessment of the RV was usually qualitative in
      nature. Current advances in echocardiographic techniques have been able to
      overcome some of the previous limitations and thus quantification of RV function
      is increasingly being performed. In addition, recent echocardiographic guidelines
      for evaluating the RV have been published to aid in standardizing practice. The
      evaluation of RV function almost certainly has no greater importance than in the
      congenital heart population, especially in those patients that have a single RV
      acting as the systemic ventricle. As this complex population continues to
      increase in number, accurate and precise evaluation of RV function will be a
      major issue in determining clinical care.

PMID- 22139358
TI  - NuRD-mediated deacetylation of H3K27 facilitates recruitment of Polycomb
      Repressive Complex 2 to direct gene repression.
AB  - Pluripotent cells possess the ability to differentiate into any cell type.
      Commitment to differentiate into specific lineages requires strict control of
      gene expression to coordinate the downregulation of lineage inappropriate genes
      while enabling the expression of lineage-specific genes. The nucleosome
      remodelling and deacetylation complex (NuRD) is required for lineage commitment
      of pluripotent cells; however, the mechanism through which it exerts this effect
      has not been defined. Here, we show that histone deacetylation by NuRD specifies
      recruitment for Polycomb Repressive Complex 2 (PRC2) in embryonic stem (ES)
      cells. NuRD-mediated deacetylation of histone H3K27 enables PRC2 recruitment and
      subsequent H3K27 trimethylation at NuRD target promoters. We propose a gene
      specific mechanism for modulating expression of transcriptionally poised genes
      whereby NuRD controls the balance between acetylation and methylation of
      histones, thereby precisely directing the expression of genes critical for
      embryonic development.

PMID- 22139361
TI  - The role of right ventricular function in the development of heart failure: what
      should we solve?

PMID- 22139362
TI  - Plakophilin-2 gene could be a causative factor in arrhythmogenic right
      ventricular cardiomyopathy.

PMID- 22139364
TI  - Clinical implications of electrocardiograms for patients with anterior wall ST
      segment elevation acute myocardial infarction in the interventional era.
AB  - Reperfusion therapy has become an established treatment for ST-segment elevation
      acute myocardial infarction (STEMI), increasing the need for early diagnosis and
      early treatment. Despite the development of diagnostic strategies, the
      electrocardiogram (ECG) plays a central role in the diagnostic pathway for STEMI
      because it is inexpensive, readily available, and noninvasive. Moreover, in the
      acute phase of STEMI, the ECG can provide useful information about the extent of
      area at risk, the degree of myocardial damage, reperfusion injury, and myocardial
      reperfusion, all of which influence infarct size. This review explores the
      clinical importance of the ECG for patients with anterior wall STEMI in the
      current interventional era.

PMID- 22139363
TI  - Early detection and prediction by biomarkers of acute kidney injury after cardiac
      surgery.

PMID- 22139365
TI  - Atomistic theory and simulation of the morphology and structure of ionic
      nanoparticles.
AB  - Computational techniques are widely used to explore the structure and properties
      of nanomaterials. This review surveys the application of both quantum mechanical
      and force field based atomistic simulation methods to nanoparticles, with a
      particular focus on the methodologies available and the ways in which they can be
      utilised to study structure, phase stability and morphology. The main focus of
      this article is on partially ionic materials, from binary semiconductors through
      to mineral nanoparticles, with more detailed considered of three examples, namely
      titania, zinc sulphide and calcium carbonate.

PMID- 22139366
TI  - Reply to Ilic et al.: the benefits of internal thoracic artery catheterization in
      patients with chronic abdominal aortic occlusion.

PMID- 22139367
TI  - Phlegmasia caerulea dolens in a patient with an inferior vena cava filter:
      treatment of massive iliocaval thrombosis using local intravenous catheter
      directed thrombolysis.
AB  - Phlegmasia caerulea dolens (PCD) is a potentially disastrous complication of
      inferior vena cava filter insertion, and its optimum management has not been
      clearly established. We present a case report of a patient with pulmonary
      embolism and acute adrenal haemorrhage who developed PCD secondary to massive
      iliocaval thrombosis after insertion of a Cook Celect removable filter. Local
      intravenous catheter-directed thrombolysis (CDT), followed by systemic
      anticoagulation, achieved limb salvage and virtual resolution of symptoms at 3
      months without complications. CDT can be a successful primary treatment of filter
      associated PCD and can be safe in selected patients with acute nontraumatic
      haemorrhage. Systemic anticoagulation may subsequently restore complete venous
      patency and may therefore be a useful approach to postthrombolysis management of
      residual iliocaval thrombus when filter removal is indicated.

PMID- 22139368
TI  - Patency of femoral tunneled hemodialysis catheters and factors predictive of
      patency failure.
AB  - PURPOSE: To determine the patency rates of and factors associated with increased
      risk of patency failure in patients with femoral vein tunneled hemodialysis
      catheters. METHODS: All femoral tunneled catheter insertions from 1996 to 2006
      were reviewed, during which time 123 catheters were inserted. Of these, 66 were
      exchanges. Patients with femoral catheter failure versus those with femoral
      catheter patency were compared. Confounding factors, such as demographic and
      procedural factors, were incorporated and assessed using univariate and
      multivariable Cox proportional hazards regression analyses. RESULTS: Mean
      catheter primary patency failure time was 96.3 days (SE 17.9 days). Primary
      patency at 30, 60, 90, and 180 days was 53.8%, 45.4%, 32.1%, and 27.1%
      respectively. Crude rates of risk of catheter failure did not suggest a benefit
      for patients receiving catheters introduced from one side versus the other, but
      more cephalad location of catheter tip was associated with improved patency.
      Multivariate analysis showed that patients whose catheters were on the left side
      (p = 0.009), were of increasing age at the time of insertion (p = 0.002) and that
      those who had diabetes (p = 0.001) were at significantly greater risk of catheter
      failure. The catheter infection rate was 1.4/1000 catheter days. CONCLUSION:
      Patients who were of a more advanced age and had diabetes were at greater risk of
      femoral catheter failure, whereas those who received femoral catheters from the
      right side were less at risk of catheter failure.

PMID- 22139369
TI  - Potent and selective activation of abscisic acid receptors in vivo by mutational
      stabilization of their agonist-bound conformation.
AB  - Pyrabactin resistance (PYR) 1 and its relatives belong to a family of soluble
      abscisic acid (ABA) receptors that inhibit type 2C protein phosphatases (PP2C)
      when in their agonist-stabilized conformation. Given their switch-like
      properties, we envisioned that mutations that stabilize their agonist-bound
      conformation could be used to activate signaling in vivo. To identify such
      mutations, we subjected PYR1 to site-saturation mutagenesis at 39 highly
      conserved residues that participate in ABA or PP2C contacts. All 741 possible
      single amino acid substitutions at these sites were tested to identify variants
      that increase basal PYR1-PP2C interactions, which uncovered activating mutations
      in 10 residues that preferentially cluster in PYR1's gate loop and C-terminal
      helix. The mutations cause measurable but incomplete receptor activation in
      vitro; however, specific triple and quadruple mutant combinations were
      constructed that promote an agonist-bound conformation, as measured by
      heteronuclear single quantum coherence NMR, and lead to full receptor activation.
      Moreover, these mutations retain functionality when introduced into divergent
      family members, and can therefore be used to dissect individual receptor function
      in vivo, which has been problematic because of redundancy and family size.
      Expression of activated PYL2 in Arabidopsis seeds activates ABA signaling by a
      number of measures: modulation of ABA-regulated gene expression, induction of
      hyperdormancy, and suppression of ABA deficiency phenotypes in the aba2-1 mutant.
      Our results set the stage for systematic gain-of-function studies of PYR1 and
      related ABA receptors and reveal that, despite the large number of receptors,
      activation of a single receptor is sufficient to activate signaling in planta.

PMID- 22139370
TI  - Arabidopsis cryptochrome 2 (CRY2) functions by the photoactivation mechanism
      distinct from the tryptophan (trp) triad-dependent photoreduction.
AB  - Cryptochromes are blue-light receptors mediating various light responses in
      plants and animals. The photochemical mechanism of cryptochromes is not well
      understood. It has been proposed that photoactivation of cryptochromes involves
      the blue-light-dependent photoreduction of flavin adenine dinucleotide via the
      electron transport chain composed of three evolutionarily conserved tryptophan
      residues known as the "trp triad." We investigated this hypothesis by analyzing
      the photochemical and physiological activities of Arabidopsis cryptochrome 2
      (CRY2) mutations altered in each of the three trp-triad residues. We found that
      all trp-triad mutations of CRY2 tested lost photoreduction activity in vitro but
      retained the physiological and biochemical activities in vivo. Some of the trp
      triad mutations of CRY2 remained responsive to blue light; others, such as
      CRY2(W374A), became constitutively active. In contrast to wild-type CRY2, which
      undergoes blue-light-dependent interaction with the CRY2-signaling proteins
      SUPPRESSOR OF PHYA 1 (SPA1) and cryptochrome-interaction basic helix-loop-helix 1
      (CIB1), the constitutively active CRY2(W374A) interacts with SPA1 and CIB1
      constitutively. These results support the hypothesis that cryptochromes mediate
      blue-light responses via a photochemistry distinct from trp-triad-dependent
      photoreduction and that the trp-triad residues are evolutionarily conserved in
      the photolyase/cryptochrome superfamily for reasons of structural integrity
      rather than for photochemistry per se.

PMID- 22139371
TI  - Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated
      phenotypes and Bbs3 unique phenotypes.
AB  - Bardet-Biedl syndrome (BBS) is a heterogeneous disorder characterized by obesity,
      retinopathy, polydactyly, and congenital anomalies. The incidence of hypertension
      and diabetes are also increased in BBS patients. Mutation of 16 genes
      independently causes BBS, and seven BBS proteins form the BBSome that promotes
      ciliary membrane elongation. BBS3 (ARL6), an ADP ribosylation factor-like small
      GTPase, is not part of the BBSome complex. The in vivo function of BBS3 is
      largely unknown. Here we developed a Bbs3 knockout model and demonstrate that
      Bbs3(-/-) mice develop BBS-associated phenotypes, including retinal degeneration,
      male infertility, and increased body fat. Interestingly, Bbs3(-/-) mice develop
      some unique phenotypes not seen in other BBS knockout models: no overt obesity,
      severe hydrocephalus, and elevated blood pressure (shared by some but not all BBS
      gene knockout mice). We found that endogenous BBS3 and the BBSome physically
      interact and depend on each other for their ciliary localization. This finding
      explains the phenotypic similarity between Bbs3(-/-) mice and BBSome subunit
      knockout mice. Loss of Bbs3 does not affect BBSome formation but disrupts normal
      localization of melanin concentrating hormone receptor 1 to ciliary membranes and
      affects retrograde transport of Smoothened inside cilia. We also show that the
      endogenous BBSome and BBS3 associate with membranes and the membrane association
      of the BBSome and BBS3 are not interdependent. Differences between BBS mouse
      models suggest nonoverlapping functions to individual BBS protein.

PMID- 22139372
TI  - Vertebrate-specific glutaredoxin is essential for brain development.
AB  - Cellular functions and survival are dependent on a tightly controlled redox
      potential. Currently, an increasing amount of data supports the concept of local
      changes in the redox environment and specific redox signaling events controlling
      cell function. Specific protein thiol groups are the major targets of redox
      signaling and regulation. Thioredoxins and glutaredoxins catalyze reversible
      thiol-disulfide exchange reactions and are primary regulators of the protein
      thiol redox state. Here, we demonstrate that embryonic brain development depends
      on the enzymatic activity of glutaredoxin 2. Zebrafish with silenced expression
      of glutaredoxin 2 lost virtually all types of neurons by apoptotic cell death and
      the ability to develop an axonal scaffold. As demonstrated in zebrafish and in a
      human cellular model for neuronal differentiation, glutaredoxin 2 controls axonal
      outgrowth via thiol redox regulation of collapsin response mediator protein 2, a
      central component of the semaphorin pathway. This study provides an example of a
      specific thiol redox regulation essential for vertebrate embryonic development.

PMID- 22139373
TI  - Algorithmic design of self-folding polyhedra.
AB  - Self-assembly has emerged as a paradigm for highly parallel fabrication of
      complex three-dimensional structures. However, there are few principles that
      guide a priori design, yield, and defect tolerance of self-assembling structures.
      We examine with experiment and theory the geometric principles that underlie self
      folding of submillimeter-scale higher polyhedra from two-dimensional nets. In
      particular, we computationally search for nets within a large set of
      possibilities and then test these nets experimentally. Our main findings are that
      (i) compactness is a simple and effective design principle for maximizing the
      yield of self-folding polyhedra; and (ii) shortest paths from 2D nets to 3D
      polyhedra in the configuration space are important for rationalizing
      experimentally observed folding pathways. Our work provides a model problem
      amenable to experimental and theoretical analysis of design principles and
      pathways in self-assembly.

PMID- 22139374
TI  - Specific recognition of linear ubiquitin chains by the Npl4 zinc finger (NZF)
      domain of the HOIL-1L subunit of the linear ubiquitin chain assembly complex.
AB  - The linear ubiquitin chain assembly complex (LUBAC) is a key nuclear factor
      kappaB (NF-kappaB) pathway component that produces linear polyubiquitin chains.
      The HOIL-1L subunit of LUBAC has been shown to bind linear chains; however,
      detailed structural and functional analyses on the binding between LUBAC and
      linear chains have not been performed. In this study, we found that the Npl4 zinc
      finger (NZF) domain of HOIL-1L specifically binds linear polyubiquitin chains and
      determined the crystal structure of the HOIL-1L NZF domain in complex with linear
      diubiquitin at 1.7-A resolution. The HOIL-1L NZF domain consists of a zinc
      coordinating "NZF core" region and an additional alpha-helical "NZF tail" region.
      The HOIL-1L NZF core binds both the canonical Ile44-centered hydrophobic surface
      on the distal ubiquitin and a Phe4-centered hydrophobic patch on the proximal
      ubiquitin, representing a mechanism for the specific recognition of linear
      chains. The NZF tail binds the proximal ubiquitin to enhance the binding
      affinity. These recognition mechanisms were supported by the accompanying in
      vitro and in vivo structure-based mutagenesis experiments.

PMID- 22139375
TI  - Early integrin binding to Arg-Gly-Asp peptide activates actin polymerization and
      contractile movement that stimulates outward translocation.
AB  - Integrin-mediated adhesions are critical for stem cell differentiation, cancer
      metastasis, and the immune response [Hynes RO (2009) Science 326:1216-1219].
      However, the mechanisms of early adhesion formation remain unclear, especially
      the effects of lateral clustering of integrins and the role of the Src family
      kinases. Using mobile Arg-Gly-Asp (RGD) peptide ligands on lipid bilayers with
      nano-fabricated physical barriers [Salaita K, et al. (2010) Science 327:1380
      1385], we observe surprising long-range lateral movements of ligated integrins
      during the process of cell spreading. Initially, RGD-activated integrin clusters
      stimulate actin polymerization that radiates from the clusters. Myosin II
      contraction of actin from adjacent clusters produces contractile pairs that move
      toward each other against barriers. Force generated by myosin II stimulates a Src
      kinase-dependent lamellipodial extension and outward movement of clusters.
      Subsequent retraction by myosin II causes inward movement of clusters. The final
      cell spread area increases with the density of periodic barriers. Early integrin
      clustering recruits adhesion proteins, talin, paxillin, and FAK, irrespective of
      force generation. However, recruitment of vinculin is only observed upon
      contraction. Thus, we suggest that integrin activation and early clustering are
      independent of lateral forces. Clustering activates Src-dependent actin
      polymerization from clusters. Myosin contraction of clusters to lines stimulates
      active spreading with outward forces from actin polymerization followed by a
      second wave of contraction. Many of these early mechanical steps are not evident
      in cells spreading on immobilized matrices perhaps because of the low forces
      involved. These observations can provide new targets to control integrin
      dependent adhesion and motility.

PMID- 22139376
TI  - IFNbeta produced by TLR4-activated tumor cells is involved in improving the
      antitumoral immune response.
AB  - Toll-like receptor (TLR) ligands may be a valuable tool to promote antitumor
      responses by reinforcing antitumor immunity. In addition to their expression in
      immune cells, functional TLRs are also expressed by many cancer cells, but their
      significance has been controversial. In this study, we examined the action of TLR
      ligands on tumor pathophysiology as a result of direct tumor cell effects. B16
      murine melanoma cells were stimulated in vitro with a TLR4 ligand (LPS-B16) prior
      to inoculation into TLR4-deficient mice (Tlr4 (lps-del)). Under such conditions,
      B16 cells yielded smaller tumors than nonstimulated B16 cells. The
      apoptosis/proliferation balance of the cells was not modified by TLR ligand
      treatment, nor was this effect compromised in immunocompromised nude mice.
      Mechanistic investigations revealed that IFNbeta was the critical factor produced
      by TLR4-activated tumor cells in mediating their in vivo outgrowth.
      Transcriptional analysis showed that TLR4 activation on B16 cells induced changes
      in the expression of type I IFN and type I IFN-related genes. Most importantly,
      culture supernatants from LPS-B16 cells improved the maturation of bone marrow
      derived dendritic cells (BMDC) from TLR4-deficient mice, upregulating the
      expression of interleukin-12 and costimulatory molecules on those cells. BMDC
      maturation was blunted by addition of an IFNbeta-neutralizing antibody. Moreover,
      tumor growth inhibition observed in LPS-B16 tumors was abrogated in IFNAR1
      deficient mice lacking a functional type I IFN receptor for binding IFN.
      Together, our findings show that tumor cells can be induced through the TLR4
      pathway to produce IFN and positively contribute to the antitumoral immune
      response.

PMID- 22139377
TI  - Arsenic trioxide treatment decreases the oxygen consumption rate of tumor cells
      and radiosensitizes solid tumors.
AB  - Arsenic trioxide (As(2)O(3)) is an effective therapeutic against acute
      promyelocytic leukemia and certain solid tumors. Because As(2)O(3) inhibits
      mitochondrial respiration in leukemia cells, we hypothesized that As(2)O(3) might
      enhance the radiosensitivity of solid tumors by increasing tumor oxygenation
      [partial pressure of oxygen (pO(2))] via a decrease in oxygen consumption. Two
      murine models of radioresistant hypoxic cancer were used to study the effects of
      As(2)O(3). We measured pO(2) and the oxygen consumption rate in vivo by electron
      paramagnetic resonance oximetry and (19)fluorine-MRI relaxometry. Tumor perfusion
      was assessed by Patent blue staining. In both models, As(2)O(3) inhibited
      mitochondrial respiration, leading to a rapid increase in pO(2). The decrease in
      oxygen consumption could be explained by an observed decrease in glutathione in
      As(2)O(3)-treated cells, as this could increase intracellular reactive oxygen
      species that can disrupt mitochondrial membrane potential. When tumors were
      irradiated during periods of As(2)O(3)-induced augmented oxygenation,
      radiosensitivity increased by 2.2-fold compared with control mice. Notably, this
      effect was abolished when temporarily clamped tumors were irradiated. Together,
      our findings show that As(2)O(3) acutely increases oxygen consumption and
      radiosensitizes tumors, providing a new rationale for clinical investigations of
      As(2)O(3) in irradiation protocols to treat solid tumors.

PMID- 22139378
TI  - Classifying human brain tumors by lipid imaging with mass spectrometry.
AB  - Brain tissue biopsies are required to histologically diagnose brain tumors, but
      current approaches are limited by tissue characterization at the time of surgery.
      Emerging technologies such as mass spectrometry imaging can enable a rapid direct
      analysis of cancerous tissue based on molecular composition. Here, we illustrate
      how gliomas can be rapidly classified by desorption electrospray ionization-mass
      spectrometry (DESI-MS) imaging, multivariate statistical analysis, and machine
      learning. DESI-MS imaging was carried out on 36 human glioma samples, including
      oligodendroglioma, astrocytoma, and oligoastrocytoma, all of different histologic
      grades and varied tumor cell concentration. Gray and white matter from glial
      tumors were readily discriminated and detailed diagnostic information could be
      provided. Classifiers for subtype, grade, and concentration features generated
      with lipidomic data showed high recognition capability with more than 97% cross
      validation. Specimen classification in an independent validation set agreed with
      expert histopathology diagnosis for 79% of tested features. Together, our
      findings offer proof of concept that intraoperative examination and
      classification of brain tissue by mass spectrometry can provide surgeons,
      pathologists, and oncologists with critical and previously unavailable
      information to rapidly guide surgical resections that can improve management of
      patients with malignant brain tumors.

PMID- 22139379
TI  - Chromogranin A regulates tumor self-seeding and dissemination.
AB  - Cancer progression involves the seeding of malignant cells in circulation and the
      colonization of distant organs. However, circulating neoplastic cells can also
      reinfiltrate the tumor of origin. This process, called "tumor-self seeding," can
      select more aggressive cells that may contribute to cancer progression. Here,
      using mouse mammary adenocarcinoma models, we observed that both tumor self
      seeding and organ colonization were inhibited by chromogranin A (CgA), a protein
      present in variable amounts in the blood of cancer patients. Mechanism studies
      showed that CgA inhibited the shedding of cancer cells in circulation from
      primary tumors, as well as the reinfiltration of tumors and the colonization of
      lungs by circulating tumor cells. CgA reduced gap formation induced by tumor cell
      derived factors in endothelial cells, decreased vascular leakage in tumors, and
      inhibited the transendothelial migration of cancer cells. Together, our findings
      point to a role for circulating CgA in the regulation of tumor cell trafficking
      from tumor-to-blood and from blood-to-tumor/normal tissues. Inhibition of the
      multidirectional trafficking of cancer cells in normal and neoplastic tissues may
      represent a novel strategy to reduce cancer progression.

PMID- 22139380
TI  - Genetic determinants for promoter hypermethylation in the lungs of smokers: a
      candidate gene-based study.
AB  - The detection of tumor suppressor gene promoter methylation in sputum-derived
      exfoliated cells predicts early lung cancer. Here, we identified genetic
      determinants for this epigenetic process and examined their biologic effects on
      gene regulation. A two-stage approach involving discovery and replication was
      used to assess the association between promoter hypermethylation of a 12-gene
      panel and common variation in 40 genes involved in carcinogen metabolism,
      regulation of methylation, and DNA damage response in members of the Lovelace
      Smokers Cohort (N = 1,434). Molecular validation of three identified variants was
      conducted using primary bronchial epithelial cells. Association of study-wide
      significance (P < 8.2 * 10(-5)) was identified for rs1641511, rs3730859, and
      rs1883264 in TP53, LIG1, and BIK, respectively. These single-nucleotide
      polymorphisms (SNP) were significantly associated with altered expression of the
      corresponding genes in primary bronchial epithelial cells. In addition, rs3730859
      in LIG1 was also moderately associated with increased risk for lung cancer among
      Caucasian smokers. Together, our findings suggest that genetic variation in DNA
      replication and apoptosis pathways impacts the propensity for gene promoter
      hypermethylation in the aerodigestive tract of smokers. The incorporation of
      genetic biomarkers for gene promoter hypermethylation with clinical and somatic
      markers may improve risk assessment models for lung cancer.

PMID- 22139381
TI  - Hypothalamic-pituitary-gonadal axis homeostasis predicts longevity.
AB  - The reproductive-cell cycle theory of aging posits that reproductive hormone
      changes associated with menopause and andropause drive senescence via altered
      cell cycle signaling. Using data from the Wisconsin Longitudinal Study (n =
      5,034), we analyzed the relationship between longevity and menopause, including
      other factors that impact "ovarian lifespan" such as births, oophorectomy, and
      hormone replacement therapy. We found that later onset of menopause was
      associated with lower mortality, with and without adjusting for additional
      factors (years of education, smoking status, body mass index, and marital
      status). Each year of delayed menopause resulted in a 2.9% reduction in
      mortality; after including a number of additional controls, the effect was
      attenuated modestly but remained statistically significant (2.6% reduction in
      mortality). We also found that no other reproductive parameters assessed added to
      the prediction of longevity, suggesting that reproductive factors shown to affect
      longevity elsewhere may be mediated by age of menopause. Thus, surgical and
      natural menopause at age 40, for example, resulted in identical survival
      probabilities. These results support the maintenance of the hypothalamic
      pituitary-gonadal axis in homeostasis in prolonging human longevity, which
      provides a coherent framework for understanding the relationship between
      reproduction and longevity.

PMID- 22139382
TI  - MUC5AC in juvenile conjunctival nevus.
AB  - PURPOSE: To evaluate the possible role of cysts with mucins and inflammatory
      cells in rapid-growing juvenile conjunctival nevus. METHODS: This was a case
      control study at a university-based referral clinic. Seventeen conjunctival
      melanocytic lesions surgically excised from patients aged <20 years between 2001
      and 2009 were examined by hematoxylin-eosin, periodic acid-Schiff, MUC5AC, and
      Alcian blue staining. The clinical signs of the affected patients and the
      histological findings were characterized. RESULTS: Eleven patients (3 girls and 8
      boys; mean age 13.72 +/- 3.60 years) underwent excision of a conjunctival nevus
      that had grown rapidly within a recent 6-month period. We found a significantly
      higher number of prominent cysts with mucins in the rapid-growing specimens than
      in the stable-growing control specimens (n = 6; 33.7 +/- 19.9 vs. 0.9 +/- 0.9%, P
      = 0.0005). However, the numbers of inflammatory cells were not statistically
      significantly different (42.17 +/- 15.46 vs. 45.55 +/- 16.31, P = 0.683).
      CONCLUSIONS: The period of rapid growth of juvenile conjunctival nevus is not a
      malignant clinical sign. Although it might correlate with enlarged cysts lined by
      goblet cells associated with mucin secretions, the number of inflammatory cells
      remains relatively stable over time.

PMID- 22139383
TI  - The antitumor effect of mesenchymal stem cells transduced with a lentiviral
      vector expressing cytosine deaminase in a rat glioma model.
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) have been recognized as promising
      delivery vehicles for gene therapy of gliomas. The purpose of this study was to
      evaluate the antitumor effect of cytosine deaminase (CD)-expressing MSCs in a rat
      C6 glioma model. METHODS: Lentiviral vectors expressing cytosine deaminase (CD)
      or enhanced green fluorescent protein (eGFP) were constructed and transduced into
      rat MSCs to generate MSC-CD/eGFP cells. By intracranially injecting C6 glioma
      cells (1 * 10(6)) alone or in combination with parental MSCs (1 * 10(6) or 2 *
      10(6)) or MSC-CD/eGFP cells (1 * 10(6) or 2 * 10(6)) into rats, we examined the
      effect of engineered MSCs on tumor growth, tumor cell apoptosis, and rat survival
      in the presence of 5-fluorocytosine (5-FC). RESULTS: MSC-CD/eGFP cells were
      largely localized at the junction of the tumor with normal tissue. The mean
      survival time of rats co-injected with C6 glioma cells and MSC-CD/eGFP cells was
      significantly extended (C6 + MSC-CD/eGFP (1:1), 32.3 days; C6 + MSC-CD/eGFP
      (1:2), 45.9 days) when compared with rats injected with C6 glioma cells alone
      (15.3 days) or those co-injected with C6 glioma cells and parental cells (C6 +
      MSCs (1:1), 16.0 days; C6 + MSCs (1:2), 16.6 days). MSC-CD/eGFP-mediated gene
      therapy significantly reduced the tumor volume in C6 glioma-bearing rats. On day
      14 after cell injection, the reduction in the mean tumor volume in rats co
      injected with C6 + MSC-CD/eGFP cells (1:1 and 1:2) was 77.24 and 83.28%,
      respectively. In addition, MSC-CD/eGFP-mediated gene therapy promoted tumor cell
      apoptosis in rat C6 gliomas. CONCLUSION: Genetically engineered MSCs have good
      therapeutic efficacy against experimental gliomas in rats.

PMID- 22139384
TI  - miR-24 functions as a tumor suppressor in Hep2 laryngeal carcinoma cells partly
      through down-regulation of the S100A8 protein.
AB  - microRNAs, a family of small non-coding RNAs, regulating approximately 30% of all
      human genes are deeply involved in the pathogenesis of several types of cancers,
      including laryngeal squamous cell carcinoma (LSCC). Here, we demonstrate that miR
      24 is down-regulated in human LSCC tissues. Ectopic expression of miR-24 in Hep2
      cells significantly induced cell morphology changes and inhibited cell
      proliferation and invasion ability in vitro by targeting S100A8 at the
      translational level. Meanwhile, miR-24 could significantly inhibit Hep2 cell
      invasion after S100A8 protein blockade. In conclusion, our results suggest that
      miR-24 may function as a tumor suppressor in LSCC through down-regulation of
      S100A8, which suggests that miR-24 could serve as a novel potential maker for
      LSCC therapy.

PMID- 22139385
TI  - Merleau-Ponty's sexual schema and the sexual component of body integrity identity
      disorder.
AB  - Body integrity identity disorder (BIID), formerly also known as apotemnophilia,
      is characterized by a desire for amputation of a healthy limb and is claimed to
      straddle or to even blur the boundary between psychiatry and neurology. The
      neurological line of approach, however, is a recent one, and is accompanied or
      preceded by psychodynamical, behavioural, philosophical, and psychiatric
      approaches and hypotheses. Next to its confusing history in which the disorder
      itself has no fixed identity and could not be classified under a specific
      discipline, its sexual component has been an issue of unclarity and controversy,
      and its assessment a criterion for distinguishing BIID from apotemnophilia, a
      paraphilia. Scholars referring to the lived body-a phenomenon primarily discussed
      in the phenomenological tradition in philosophy-seem willing to exclude the
      sexual component as inessential, whereas other authors notice important
      similarities with gender identity disorder or transsexualism, and thus precisely
      focus attention on the sexual component. This contribution outlines the history
      of BIID highlighting the vicissitudes of its sexual component, and questions the
      justification for distinguishing BIID from apotemnophilia and thus for omitting
      the sexual component as essential. Second, we explain a hardly discussed concept
      from Maurice Merleau-Ponty's Phenomenology of Perception (1945a), the sexual
      schema, and investigate how the sexual schema could function in interaction with
      the body image in an interpretation of BIID which starts from the lived body
      while giving the sexual component its due.

PMID- 22139386
TI  - One or two types of death? Attitudes of health professionals towards brain death
      and donation after circulatory death in three countries.
AB  - This study examined health professionals' (HPs) experience, beliefs and attitudes
      towards brain death (BD) and two types of donation after circulatory death (DCD)-
      controlled and uncontrolled DCD. Five hundred and eighty-seven HPs likely to be
      involved in the process of organ procurement were interviewed in 14 hospitals
      with transplant programs in France, Spain and the US. Three potential donation
      scenarios--BD, uncontrolled DCD and controlled DCD--were presented to study
      subjects during individual face-to-face interviews. Our study has two main
      findings: (1) In the context of organ procurement, HPs believe that BD is a more
      reliable standard for determining death than circulatory death, and (2) While the
      vast majority of HPs consider it morally acceptable to retrieve organs from brain
      dead donors, retrieving organs from DCD patients is much more controversial. We
      offer the following possible explanations. DCD introduces new conditions that
      deviate from standard medical practice, allow procurement of organs when donors'
      loss of circulatory function could be reversed, and raises questions about
      "death" as a unified concept. Our results suggest that, for many HPs, these
      concerns seem related in part to the fact that a rigorous brain examination is
      neither clinically performed nor legally required in DCD. Their discomfort could
      also come from a belief that irreversible loss of circulatory function has not
      been adequately demonstrated. If DCD protocols are to achieve their full
      potential for increasing organ supply, the sources of HPs' discomfort must be
      further identified and addressed.

PMID- 22139387
TI  - A comparison of percutaneous reduction and screw fixation versus open reduction
      and plate fixation of traumatic symphysis pubis diastasis.
AB  - PURPOSE: Plate fixation, the conventional treatment for traumatic symphysis pubis
      diastasis, carries the risk of extensive exposure, blood loss and postoperative
      infections. Percutaneous screw fixation is a minimally invasive treatment. The
      goal of the present study was to compare the outcome of plate fixation and
      percutaneous screw technique in the treatment of traumatic pubic symphysis
      diastasis. METHODS: Ninety patients with traumatic symphysis pubis diastasis were
      treated from January 2003 to December 2009 at two level 1 regional trauma
      centers. The mean time of follow-up was 21 months (18 to 26). Forty-five patients
      were treated by percutaneous screw fixation. Forty-five patients were treated by
      plate and screws fixation. The demographic, distribution of fracture patterns,
      blood loss, incision length, fixation failure, malunion, revision surgery and
      functional scores were compared. RESULTS: Seven cases were lost during follow-up.
      Demographics (age and gender), fracture classification and Injury Severity Score
      were comparable in the two groups (P > 0.05). Blood loss and extensive exposure
      were much less in screw group (P < 0.01). Patients in screw group achieved better
      functional performance (P = 0.01). There were no significant differences favoring
      plate fixation in reduction quality (P = 0.32), implant failure (P = 0.39),
      malunion (P = 0.15), revision surgery rates (P = 0.27), percentage of impotence
      in the male patients (P = 0.2) and implant removal time (P = 0.12) between the
      two groups. CONCLUSIONS: Our results indicate that besides lower rate of
      iatrogenic injuries and better functional outcome, percutaneous screw fixation of
      the pubic symphysis is as strong as plate fixation.

PMID- 22139388
TI  - Clinical characteristics and surgical outcome of the symptomatic ossification of
      ligamentum flavum at the thoracic level with combined lumbar spinal stenosis.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To identify the clinical
      significance of coexistence of lumbar spinal stenosis (LSS) with thoracic
      ossification of ligamentum flavum (OLF), and to study the surgical outcome of the
      thoracic OLF patients with or without LSS. SUMMARY OF BACKGROUND DATA: The OLF at
      the thoracic level (thoracic OLF) is a rare disease that causes acquired thoracic
      spinal canal stenosis. Thoracic OLF is frequently combined with other spinal
      disorders, such as LSS, and it is not uncommon for thoracic OLF to be
      misdiagnosed as LSS, resulting in delayed diagnosis. However, clinical impacts of
      the coexistence of LSS with thoracic OLF remain unknown. METHODS: In the present
      study, 36 patients who underwent posterior decompression for OLF-induced thoracic
      myelopathy were retrospectively reviewed, and the adverse influence of the
      copresence of LSS with thoracic OLF was studied with regard to clinical features
      such as clinical symptoms and surgical outcome. RESULTS: Out of 36 patients, 18
      patients had LSS (combined group: C-group), and the remaining 18 patients had
      thoracic OLF only (thoracic group: T-group). No significant inter-group
      differences were found in terms of gender, age, follow-up period, and
      preoperative duration of symptoms. Regarding the etiology of LSS in the C-group,
      12 cases had degenerative LSS, two cases had lumbar OLF, one case had
      degenerative LSS with lumbar OLF, one case had had degenerative LSS with lumbar
      OPLL, and two cases had traumatic LSS due to lumbar kyphosis after vertebral
      fracture. Clinical examination revealed that the T-group was significantly more
      likely to demonstrate Achilles hyper-reflexia, while the C-group was
      significantly more likely to demonstrate Achilles hypo-reflexia. The mean
      preoperative and postoperative JOA scores were not statistically different
      between the two groups. However, the mean recovery rate of the JOA score was
      17.3% in the C-group, and 30.4% in the T-group. Statistical analysis revealed
      that the recovery rate of the C-group was significantly lower than that of the T
      group. CONCLUSION: Thoracic OLF with LSS will show a more severe clinical
      manifestation than that without LSS. In this study, we clearly indicated that the
      coexisting LSS in thoracic OLF will have adverse effects on the surgical results
      in thoracic OLF.

PMID- 22139389
TI  - Formaldehyde-induced keratopathy after strabismus surgery.
AB  - We report on a patient who developed corneal haze and permanent ptosis after
      strabismus surgery. Formaldehyde-disinfected sodium hyaluronate which was used to
      protect the corneal epithelium during surgery was thought to have induced
      keratopathy and other findings. To our knowledge, this is the first report of
      corneal haze formation together with ptosis secondary to formaldehyde toxicity as
      a complication of strabismus surgery.

PMID- 22139390
TI  - A phase I study of amrubicin and fixed dose of irinotecan (CPT-11) in relapsed
      small cell lung cancer: Japan multinational trial organization LC0303.
AB  - PURPOSE: To determine the maximum tolerated dose of amrubicin (AMR) with a fixed
      dose of irinotecan (CPT-11). METHODS: Patients having pathologically proven small
      cell lung cancer (SCLC) relapsed after one or two chemotherapies, and Eastern
      Cooperative Oncology Group performance status of 0 to 2 were eligible for the
      study. CPT-11 was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was
      delivered on day 1. Doses of AMR were level 1: 80 mg/m2, level 2: 90 mg/m2, and
      level 3: 100 mg/m2. Dose elevation was determined using the modified continuous
      reassessment method. Tolerability was assessed after the first cycle. Another two
      cycles were conducted when disease progression or unacceptable toxicities were
      not observed. RESULTS: Eighteen patients (mean age: 66.3 years) were enrolled. A
      total of 40 courses were conducted. Grade 3/4 toxicities of the first cycle were
      leukocytopenia: 11 (61%, grade 3/4: 8/3); neutropenia: 15 (83%, grade 3/4: 6/9);
      and thrombocytopenia: three (17%, grade 3/4: 2/1). Other grade 3 toxicities
      observed were febrile neutropenia, one; infection, three; diarrhea, one; and
      dyspnea, one. Dose-limiting toxicity was observed in two of six patients at level
      2 (neutropenia and febrile neutropenia) and in one of six at level 3
      (thrombocytopenia and infection). The maximum tolerated dose was level 3, and so,
      the recommended dose for phase II trials was judged to be 90 mg/m2. Objective
      response was obtained in four of eight patients who were able to evaluate
      responses. Median survival time was 13 months, with 68% at 1-year survival rate.
      CONCLUSIONS: This combination was well tolerated and showed encouraging
      activities in SCLC. Randomized phase II trials are being planned in chemonaive
      SCLC.

PMID- 22139392
TI  - PAR-1/MARK: a kinase essential for maintaining the dynamic state of microtubules.
AB  - The serine/threonine kinase, PAR-1, is an essential component of the evolutionary
      conserved polarity-regulating system, PAR-aPKC system, which plays indispensable
      roles in establishing asymmetric protein distributions and cell polarity in
      various biological contexts (Suzuki, A. and Ohno, S. (2006). J. Cell Sci., 119:
      979-987; Matenia, D. and Mandelkow, E.M. (2009). Trends Biochem. Sci., 34: 332
      342). PAR-1 is also known as MARK, which phosphorylates classical microtubule
      associated proteins (MAPs) and detaches MAPs from microtubules (Matenia, D. and
      Mandelkow, E.M. (2009). Trends Biochem. Sci., 34: 332-342). This MARK activity of
      PAR-1 suggests its role in microtubule (MT) dynamics, but surprisingly, only few
      studies have been carried out to address this issue. Here, we summarize our
      recent study on live imaging analysis of MT dynamics in PAR-1b-depleted cells,
      which clearly demonstrated the positive role of PAR-1b in maintaining MT dynamics
      (Hayashi, K., Suzuki, A., Hirai, S., Kurihara, Y., Hoogenraad, C.C., and Ohno, S.
      (2011). J. Neurosci., 31: 12094-12103). Importantly, our results further revealed
      the novel physiological function of PAR-1b in maintaining dendritic spine
      morphology in mature neurons.

PMID- 22139391
TI  - Video-assisted mediastinoscopy in superior vena cava obstruction: to fear or not
      to fear?
AB  - INTRODUCTION: We investigate the safety and efficacy of video-assisted
      mediastinoscopy (VAM) used for diagnosis of the superior vena cava syndrome.
      METHODS: In a 7-year period, we have done 447 VAM for malignant causes. We have
      compared, in a retrospective study from a prospectively maintained database, the
      differences between the groups with (first group) or without (second group)
      superior vena cava syndrome in terms of operative time, preoperative and
      postoperative complications, and results of pathologic examination. Statistical
      differences between the groups were calculated by chi2 test. RESULTS: Mean
      operative time for first (31 patients) and second (416 patients) groups was 18
      and 34 minutes, respectively (p < 0.00). Mean hospital stay was 1.2 days in both
      the groups. Mortality rates for the first and second groups were 0 and 0.5% (p =
      0.31); major morbidity rates were 0 and 0.7% (p = 0.50); and minor morbidity
      rates were 6.4 and 1.7% (p = 0.27), respectively. In the superior vena cava
      syndrome group, most of the lymph nodes biopsied were in paratracheal superior
      sites (81%); histology showed small cell lung cancer in 51.6%, non-small cell
      lung cancer in 25.8%, and lymphoma in 22.6%. CONCLUSIONS: VAM represents an
      important diagnostic tool in superior vena cava syndrome. Once decided to be
      used, we think that video technique is a good option with high rate of efficacy
      and low rates of mortality and morbidity.

PMID- 22139393
TI  - [Influence of spinal orthosis on gait and physical functioning in women with
      postmenopausal osteoporosis].
AB  - INTRODUCTION: Osteoporosis is a widespread chronic bone disease leading to an
      increased risk of bone fractures. The most common clinical consequences are back
      pain, hyperkyphosis, limitations of physical functioning and activities of daily
      living as well as reduced quality of life. Furthermore, osteoporosis is
      associated with decreased strength and deficits of gait and balance, all together
      resulting in an increased risk of falls and a subsequent aggravation of fracture
      risk. Besides pharmaceutical and exercise therapy, back orthoses are increasingly
      being used in the therapy of osteoporosis and rehabilitation after vertebral
      fractures. Previous studies have shown that wearing a spinal orthosis results in
      a reduction of pain as well as improvements of posture and back extensor
      strength. To date there is no study that has evaluated the effects of a spinal
      orthosis on gait stability and physical functioning in patients with
      osteoporosis. Therefore the purpose of the present study was to assess the
      effects of a spinal orthosis on gait and pain-induced limitations of activities
      of daily living (ADL) in women with osteoporosis. METHODS: A total of 69
      postmenopausal osteoporotic women with and without vertebral fractures were
      randomly assigned to receive either a spinal orthosis (Thamert Osteo-med
      intervention group n=35; average age 74 +/- 8.3 years, height 158.3 +/- 6.3 cm,
      weight 62.8 +/- 9.6 kg, t-score -2.6  +/- 1.0, number of vertebral fractures 1.4
      +/- 2.0) or to a waiting list control group (n= 34, age 74.1 +/- 7.7 years,
      height 159.6 +/- 5.9 cm, weight 65.4 +/- 11.3 kg, t-score -2.9+/- 0.8, number of
      vertebral fractures: 0.9 +/- 1.2). The following outcome measures were collected
      at baseline and at 3 and 6 months follow-up: gait parameters including gait
      analysis: velocity, stride length and width, double support time (% of gait
      cycle) and perceived limitations in activities of daily living (numeric rating
      scale 1-10; 1=best, 10= worst situation). RESULTS: The ANCOVA indicated a
      significant reduction of the double support time at 6 months in the intervention
      group (p < 0.05) without a significant influence of the covariate vertebral
      fractures status. The other parameters remained unchanged (p > 0 .05). Regarding
      the pain-related ADL limitations there were significant differences in the amount
      of change over the study period depending on the baseline value. Stratified into
      terciles (<= 2.5; 2.6-5.0; >5) patients with initially high values showed a
      significantly greater reduction in perceived ADL restrictions compared to
      patients in the lowest tercile (-2.7 +/- 2.7 versus 1.5 +/- 2.1). CONCLUSION: The
      study demonstrated that wearing a spinal orthosis introduced a reduction in
      double support time associated with a beneficial impact on gait stability.
      Furthermore, there was a positive effect on pain-related restrictions of ADL
      evident in women with a high level of limitations at baseline. Besides previously
      shown reductions in pain, improvements in back extensor strength and correction
      of posture, the application of a spinal orthosis may induce advantages for gait
      stability and physical functioning in women with postmenopausal osteoporosis.
      Future studies should consider a longer follow-up to evaluate possible effects on
      the risk of falling and fractures.

PMID- 22139394
TI  - Morphology of flexor digitorum accessorius muscle.
AB  - PURPOSE: Muscle flexor digitorum accessorius is the muscle of the second layer of
      the sole. It arises by two heads and gets inserted into the tendon of flexor
      digitorum longus muscle. A variant of this muscle has often been incriminated in
      causation of tarsal tunnel syndrome. The action and phylogenetic importance of
      this muscle remains a matter of disagreement among different researchers. The
      present study was planned to study the morphology of this muscle in human.
      METHOD: The second layer of the sole was dissected in forty-seven cadavers.
      Origin, insertion and any variations of this muscle were observed. Extension of
      origin of medial head of this muscle into the tarsal tunnel was also observed.
      RESULTS: The muscle was found to be very variable. The medial head was more
      variable, ranging from the complete absence to the bulky fleshy origin. It had
      fleshy origin from medial surface of calcaneus that extended deep to medio
      malleolo calcaneal axis, i.e. into the tarsal tunnel in 80% of the cases. The
      lateral head was relatively constant and its origin was aponeurotic in all the
      cases. Insertion of this muscle was very variable, the commonest being insertion
      on the deep surface of flexor digitorum longus tendon. An accessory muscle-flexor
      digitorum accessorius longus-was observed in two cases. CONCLUSION: The bulky
      medial head appears to be assuming the function of primary toe flexor in the
      plantigrade man. The origin of medial head extends into the tarsal tunnel in
      majority. A bulky medial head should be considered as a possible cause of tarsal
      tunnel syndrome.

PMID- 22139395
TI  - The anatomy of proximal femoral autografts for pelvic reconstruction: a cadaveric
      study.
AB  - PURPOSE: One important reconstruction procedure following pelvic tumor resection
      is ipsilateral femoral autograft reconstruction in which the autograft is
      transposed onto the defect and a conventional total hip replacement is implanted
      in the autograft. The purpose of this study is to provide anatomical evidence for
      this reconstruction by measurement of proximal femoral autografts. METHODS: The
      anatomical study of proximal femoral autografts was performed on thirteen fresh
      frozen Chinese male cadavers. Four parameters were measured and included the
      diameter of the femoral head (DFH), the distance from the apex of the greater
      trochanter perpendicular to the medial cortex edge of the femoral neck (DAM), the
      length between the apex of the femoral head and the midpoint of osteotomy line
      under the lesser trochanter (LAM), and the width of the greater trochanter from
      anterior to posterior (WG). The correlation between height and each of the
      various parameters was analyzed using the Spearman's correlation. RESULTS: The
      median (first and third quartile) values of the measurements for the above
      mentioned parameters were 49 mm (48-52.7 mm), 58.5 mm (54.5-60.9 mm), 102 mm (96
      105.2 mm) and 48 mm (46.5-51 mm), respectively. There was a positive correlation
      between height and each of these four parameters (P < 0.05). CONCLUSIONS: The
      proximal femoral autograft reconstruction may be a good option after resection of
      a pelvic tumor because of the provision of biological reconstruction. However, an
      individual preoperative plan should be carefully performed following evaluating
      the size of the bone defect after tumor resection and height and width of the
      remaining greater trochanter prior to conventional hip replacement.

PMID- 22139397
TI  - Synthesis of novel 4H-pyrimido[1,6-a]pyrimidines via a one-pot three-component
      condensation.
AB  - Highly substituted novel 4H-pyrimido[1,6-a] pyrimidines were prepared by a
      trifluoromethanesulfonic acid catalyzed one-pot three-component condensation of 4
      aminopyrimidines, aldehydes, and beta-ketoesters. A preliminary feasibility study
      was undertaken on these compounds, to assess the potential production of a
      library of further diversified compounds by nucleophilic replacement of Cl(R(1))
      or by reaction of electrophiles with the NH(2)(R(2)) group.

PMID- 22139398
TI  - Experimental and modeling study of carbon suboxide decomposition behind reflected
      shock waves.
AB  - At temperatures between 1150 and 2000 K and pressures between 0.1 and 0.2 MPa,
      the thermal decomposition of carbon suboxide (C(3)O(2)) behind reflected shock
      waves was investigated with a high-repetition-rate time-of-flight mass
      spectrometer (HRR-TOF-MS) connected to the end flange of a shock tube enabling
      rapid repetitive (100 kHz) measurements of the gas-phase composition.
      Concentration-time profiles for C(3)O(2) and CO were measured and compared to
      simulations based on an improved mechanism for C(3)O(2) decomposition and carbon
      cluster growth. In addition, relative concentrations of C atoms and C(2)
      molecules were detected and related to model predictions. For temperatures up to
      1800 K, satisfactory agreement between experimental data and calculations was
      obtained. At higher temperatures, measurements and simulations differed
      noticeably. The importance of C(2) for the growth of carbon clusters was
      confirmed.

PMID- 22139396
TI  - The role of lymphatics in cancer as assessed by near-infrared fluorescence
      imaging.
AB  - The lymphatic system is the secondary circulatory system responsible for fluid
      homeostasis and protein transport in the body. In addition, because the lymphatic
      system provides a primary pathway for cancer metastasis, lymph node involvement
      is routinely used as a determinant in cancer staging. Despite their importance,
      the lymphatics remain poorly understood, in part because of the historic lack of
      imaging modalities with sufficient spatial and/or temporal resolution to
      visualize the fine lymphatic structure and subtle contractile function. In recent
      years, near-infrared fluorescence (NIRF) imaging has emerged as a new imaging
      modality to non-invasively visualize the lymphatics and assess contractile
      lymphatic function in humans following administration of microdose amounts of a
      NIRF contrast agent. In this contribution, we first review NIRF imaging and its
      clinical application in sentinel lymph node mapping, intraoperative guidance, and
      assessing the architecture and contractile function of the lymphatics in health
      and in cancer-related lymphedema. We then present recent NIRF lymphatic imaging
      for non-invasive assessment of lymphatics both in preclinical melanoma models and
      in human subjects with melanoma.

PMID- 22139399
TI  - Photooxidative cleavage of zinc 20-substituted chlorophyll derivatives:
      conformationally P-helix-favored formation of regioselectively 19-20 opened
      linear tetrapyrroles.
AB  - Photoreaction of zinc methyl 20-substituted meso(pyro)pheophorbide-a prepared by
      modifying naturally occurring chlorophyll-a in the presence of oxygen molecules
      gave its C19-C20 oxidative cleavage (1-carbonyl-19-oxo-bilatrienes) as the major
      products and the regioisomeric C1-C20 cleavage (19-carbonyl-1-oxo-bilatrienes) as
      the minor products. The resulting zinc complexes of linear tetrapyrroles took a
      helical conformation and the P-conformers were preferential over the M
      stereoisomers due to the presence of their 17S,18S-chiral centers. The helical
      conformers (diastereomers) of the corresponding nickel complexes were separated
      by reverse-phase or chiral HPLC and their conformational changes were observed in
      solution.

PMID- 22139400
TI  - Membrane mediated regulation in free peptides of HIV-1 gp41: minimal modulation
      of the hemifusion phase.
AB  - Membrane-mediated structural modulation in two short fragments of the human HIV-1
      envelope protein gp41 is demonstrated. Derived from the C-terminal membrane
      proximal external (MPE) and N-terminal fusion peptide proximal (FPP) regions,
      these peptides are widely separated in the primary sequence but form tertiary
      contacts during the intermediate (hemifusion) phase of HIV infection. The
      structural perturbations observed at the membrane interface offer evidence of
      rudimentary regulatory mechanisms operating in the free peptides which may be
      relevant in the biological system. No such regulatory phenomena were observed for
      the individual peptides in a membrane environment or between the peptides in
      aqueous solutions. Structure determination is made using a combination of
      circular and linear dichroism spectroscopy (supported by calorimetric
      measurements) and molecular dynamics simulations. Specifically, we show that
      these peptides interact locally without the conformational support of helical
      heptad repeat regions in native gp41 and that the modulation is not mutual with
      the FPP peptide operating as a primary regulator of the MPE-FPP interactions in
      the hemifusion phase.

PMID- 22139401
TI  - Socially anxious and peer-victimized preadolescents: "doubly primed" for
      distress?
AB  - We examined independent and interactive associations linking preadolescents'
      socially anxious feelings and peer victimization experiences with their social
      behaviors (rated by parents and teachers) and psychophysiological arousal during
      lab simulations of salient peer stress situations in preadolescence (peer
      evaluation and peer rebuff). Sixty-three preadolescents and one parent per
      preadolescent participated. Respiratory sinus arrhythmia (RSA), skin conductance
      level (SCL), and heart rate (HR) were assessed during peer stress situations.
      Preadolescents provided reports of social anxiety; preadolescents and parents
      reported on peer victimization; and parents and teachers rated prosocial and
      aggressive behaviors. Peer victimization moderated associations between social
      anxiety and both physiological arousal and social-behavior problems. As
      hypothesized, social anxiety was more strongly associated with lower RSA, higher
      HR, and higher aggressive behavior among preadolescents who experienced higher
      levels of peer victimization, compared to preadolescents who experienced lower
      levels of peer victimization.

PMID- 22139402
TI  - Infection levels and diversity of anisakid nematodes in blackspot seabream,
      Pagellus bogaraveo, from Portuguese waters.
AB  - The blackspot seabream, Pagellus bogaraveo, is a sparid fish of great economic
      importance in the northeast Atlantic. The main aim of this work was to assess the
      infection levels and diversity of anisakid nematodes parasitizing P. bogaraveo
      from Portuguese waters. The anisakid larvae were identified by polymerase chain
      reaction-restriction fragment length polymorphism analysis and ten different
      patterns were observed, four of which were not previously reported in the
      literature. Moreover, several species were detected for the first time in this
      host: Anisakis simplex * Anisakis pegreffii hybrids, Anisakis ziphidarum,
      Anisakis typica, Anisakis physeteris, as well as three undescribed anisakids
      Anisakis sp. PB-2009, Anisakis sp. PB-2010, and Contracaecum sp. PB-2010. The
      ITS1-5.8S-ITS2 region was sequenced and analyzed phylogenetically, revealing that
      our anisakids were distributed by the two distinct clades reported previously,
      corresponding to the two recognized larval morphotypes. Moreover, a group of
      organisms, including our specimens from Madeira and the previously reported
      Anisakis sp. HC-2005, cluster together and seem to belong to clade I. A certain
      degree of intraspecific diversity was also detected. Samples from mainland waters
      had the highest infection levels and were dominated by A. pegreffii. Madeira had
      the highest diversity overall, dominated by Anisakis sp. PB-2010. Fish from the
      Azores had the lowest infection levels, and the species with the highest relative
      abundance was A. physeteris. The anisakid nematode communities were relatively
      similar in mainland waters but very distinct in both the Azores and Madeira
      islands, suggesting the existence of at least three different stocks of P.
      bogaraveo in the northeast Atlantic.

PMID- 22139403
TI  - Chemical composition and larvicidal activity of essential oil from Mentha spicata
      (Linn.) against three mosquito species.
AB  - Mosquitoes are blood-feeding insects and serve as the most important vectors for
      spreading human diseases such as malaria, yellow fever, dengue fever, and
      filariasis. The continued use of synthetic insecticides has resulted in
      resistance in mosquitoes. Synthetic insecticides are toxic and affect the
      environment by contaminating soil, water, and air, and then natural products may
      be an alternative to synthetic insecticides because they are effective,
      biodegradable, eco-friendly, and safe to environment. Botanical origin may serve
      as suitable alternative biocontrol techniques in the future. Mentha spicata, an
      edible and medicinal plant, is chiefly distributed in Southeast Asia and South
      Asia. In the present study, the toxicity of mosquito larvicidal activity of leaf
      essential oil (EO) and their major chemical constituents from Mentha spicata
      against Culex quinquefasciatus, Aedes aegypti, and Anopheles stephensi. The
      chemical composition of the leaf EO was analyzed using gas chromatography-mass
      spectroscopy (GC-MS). GC-MS revealed that the EO of M. spicata contained 18
      compounds. The major chemical components identified were carvone (48.60%), cis
      carveol (21.30%), and limonene (11.30%). The EO had a significant toxic effect
      against early third-stage larvae of C. quinquefasciatus, A. aegypti, and A.
      stephensi with LC(50) values of 62.62, 56.08, and 49.71 ppm and LC(90) values of
      118.70, 110.28, and 100.99 ppm, respectively. The three major pure constituents
      extracted from the M. spicata leaf EO were also tested individually against three
      mosquito larvae. The LC(50) values of carvone, cis-carveol, and limonene appeared
      to be most effective against A. stephensi (LC(50) 19.33, 28.50, and 8.83 ppm)
      followed by A. aegypti (LC(50) 23.69, 32.88, and 12.01 ppm), and C.
      quinquefasciatus (LC(50) 25.47, 35.20, and 14.07 ppm). The results could be
      useful in search for newer, safer, and more effective natural larvicidal agents
      against C. quinquefasciatus, A. aegypti, and A. stephensi.

PMID- 22139404
TI  - Estrogen therapy initiated at an early age increases bone mineral density in
      Turner syndrome patients.
AB  - Patients with Turner syndrome (TS) almost develop osteoporosis, resulting from
      chromosomal deficiency and estrogen deficiency by gonadal dysgenesis. The aim of
      this study was to assess bone mineral density (BMD) during continuous estrogen
      therapy in young TS patients by measuring lumbar spine BMD of 67 TS patients
      using dual-energy X-ray absorptiometry. Twenty-seven patients who were treated
      with adult-doses of estrogen prior to the first evaluation, exhibited a
      significantly higher initial BMD than 30 patients treated with low-dose estrogen
      therapy and 10 patients without estrogen therapy (0.808 g/cm2, 0.714 g/cm2, and
      0.664 g/cm2, respectively). During continuous adult-dose estrogen therapy, BMD
      significantly increased in each group (maximum BMD during the study, 0.842 g/cm2,
      0.790 g/cm2, and 0.724 g/cm2, respectively). Initial and maximum BMD showed
      significant negative correlation with the age at which adult-dose estrogen
      therapy was initiated (r = -0.57 and -0.45, respectively). Among the patients not
      treated with adult-dose estrogen therapy prior to the first evaluation, the
      annual increase in the rate and amount of BMD was significantly higher when adult
      dose estrogen therapy was initiated before age 18 (rate, 4.4 % before age 18 vs.
      3.1 % after age 18; amount, 0.03 g/cm2 before age 18 vs. 0.02 g/cm2 after age
      18). In summary, estrogen therapy increased BMD in young TS patients and might be
      more effective if initiated by age 18.

PMID- 22139405
TI  - Clinical significance of circulating platelet-activating factor acetylhydrolase
      levels in systemic sclerosis.
AB  - Platelet-activating factor acetylhydrolase (PAF-AH) has been demonstrated to be
      one of anti-inflammatory and anti-apoptotic factors, suggesting the potential to
      be involved in the development of systemic sclerosis (SSc). The aim of this study
      is to determine serum PAF-AH levels and their clinical associations in patients
      with SSc. Serum PAF-AH levels were examined by enzyme-linked immunosorbent assay
      in 57 patients with SSc and 24 healthy individuals. Serum PAF-AH levels were
      significantly elevated in SSc patients (130.4 +/- 69.5 ng/ml) compared with
      healthy individuals (81.6 +/- 34.8 ng/ml; P < 0.001). Among SSc patients, there
      were no differences in serum PAF-AH levels between those with diffuse cutaneous
      SSc (135.5 +/- 79.3 ng/ml; n = 29) and those with limited cutaneous SSc (125.1 +/
      58.6 ng/ml; n = 28). Patients with SSc who had raised PAF-AH levels less often
      had digital ulcers and arthritis/arthralgias than those with normal PAF-AH
      levels. The results show that serum PAF-AH levels were increased in patients with
      SSc and associated with a lower frequency of pitting scars/digital ulcers and
      arthritis/arthralgias. PAF-AH could be a protective factor against the
      development of digital ulcers and arthritis/arthralgia in this disease and as
      such would be a useful serological marker for disease severity.

PMID- 22139406
TI  - A bone-seeking clone exhibits different biological properties from the ACHN
      parental human renal cell carcinoma in vivo and in vitro.
AB  - Metastatic bone disease caused by renal cell carcinoma (RCC) occurs frequently.
      Very little is currently known about the mechanism of preferential metastasis of
      RCC to bone. We hypothesize that RCCs that develop bone metastases have the
      capacity to facilitate their colonization in bone. To examine this hypothesis, we
      established bone-seeking (ACHN-BO) clones of the human RCC cell line ACHN by
      repeated four passages in nude mice and in vitro of metastatic cells obtained
      from bone. These clones were examined for distinguishing biological
      characteristics and compared with the ACHN parental cells (ACHN-P) in vivo and in
      vitro. Our results showed that the ACHN-BO cell line could be successfully
      obtained by in vivo selection through the lateral tail vein. This approach
      results in the development of multiple osteolytic lesions in the distal femora
      and proximal tibiae within four weeks after inoculation, with a success rate of
      85-100% and no additional comorbidity. ACHN-P cells developed metastases in lung,
      bone, brain, ovary and adrenal glands. Conversely, ACHN-BO cells exclusively
      metastasized to bones with larger osteolytic lesions. Compared with the ACHN-P
      cell line, the proliferation ability in ACHN-BO6 was increased by 9.68 and 6.42%,
      respectively (P<0.05), while the apoptotic ratio decreased significantly (P<0.05)
      and cells were blocked in the S phase with suppressed migration and invasion
      capacities. The ACHN-BO6 cell line produced greater amounts of the pro-angiogenic
      factors VEGF and TGF-beta than ACHN-P. Our data suggest that these phenotypic
      changes allow RCC cells to promote osteoclastic bone resorption, survive and
      proliferate in bone, which consequently leads to the establishment of bone
      metastases. This model provides a reliable reproduction of the clinical situation
      and, therefore, is suitable for designing and evaluating more effective
      treatments for RCC bone metastasis.

PMID- 22139407
TI  - Pretzel knot compared with standard suture knots.
AB  - PURPOSE: Aim of this paper is to compare the biomechanical properties of the
      Pretzel knot with the selected arthroscopic knots and to test the mechanical
      safety of this knot. The hypothesis was that the Pretzel knot may have equal or
      better mechanical properties than the arthroscopic knots tested in this study.
      METHODS: SMC, Giant, Dines, Nicky's, Tennessee Slider knots were chosen for
      comparison. Original and backed configuration of knots were prepared with no. 2
      braided polyester sutures. Cyclic loading and load to failure tests were
      performed. Parameters tested were loop security, maximum elongation and load at
      failure. Number of steps needed for preparation of each knot was also recorded.
      One-way ANOVA for repeated measures was performed for all knots. RESULTS: Steps
      needed for preparation were 2 for Pretzel and Tennessee Slider, 3 for Nicky's,
      SMC and Dines and 4 for Giant. The Pretzel knot in original configuration had
      significantly better loop security compared to SMC, Dines, Nicky's and Tennessee
      knots (P = 0.01). Loads at failure were not significantly different between knots
      in their original configurations. Giant and Dines knots showed better maximum
      elongations in cyclic loading (P = 0.0059) and load to failure tests (P =
      0.0001). Backing up the knots with 3-RHAPs eliminated most of these significant
      differences. CONCLUSIONS: Clinically, simplicity and safety are two important
      components in arthroscopic knot tying. Despite its simple configuration, Pretzel
      knot has some similar and increased mechanical properties compared to the tested
      knots that are widely used.

PMID- 22139408
TI  - Quadriceps femoris muscle function prior and after total knee arthroplasty in
      women with knee osteoarthritis.
AB  - PURPOSE: The aim of the present study was to evaluate an isometric voluntary
      force generation and relaxation capacity of the quadriceps femoris (QF) muscle
      prior and after total knee arthroplasty (TKA). METHODS: Isometric maximal
      voluntary contraction force, rate of force development, voluntary activation,
      half-relaxation time, and latency of contraction of the QF muscle were recorded
      in 12 female patients (aged 49-68 years) with knee osteoarthritis one day before,
      3 and 6 months following TKA in the operated and nonoperated leg. Knee pain
      intensity was assessed by visual analog scale, and Knee injury and Osteoarthritis
      Outcome Score (KOOS) questionnaire was used to assess knee problems during daily
      living. RESULTS: A significant decrease in knee pain and significant increase in
      KOOS were established after TKA. Maximal voluntary isometric force in the
      operated leg was lower (P < 0.05) before, 3 and 6 months after TKA as compared to
      the nonoperated leg. Rate of force development of the QF muscle in the operated
      leg compared to the nonoperated leg was significantly lower (P < 0.05) 3 and 6
      months after TKA. Voluntary activation, latency of contraction, and half
      relaxation time of the QF muscle did not differ significantly before, 3 and 6
      months after TKA. CONCLUSIONS: The present study indicated reduced maximal and
      explosive strength of quadriceps femoris muscle in the operated leg 3 and 6
      months after TKA with no significant changes in voluntary activation, and
      capacity for rapid contraction and relaxation. LEVEL OF EVIDENCE: Prospective
      comparative study, Level II.

PMID- 22139409
TI  - Aloin enhances cisplatin antineoplastic activity in B16-F10 melanoma cells by
      transglutaminase-induced differentiation.
AB  - Aloin, a natural anthracycline from aloe plant, is a hydroxyanthraquinone
      derivative shown to have antitumor properties. This study demonstrated that aloin
      exerted inhibition of cell proliferation, adhesion and invasion abilities of B16
      F10 melanoma cells under non-cytotoxic concentrations. Furthermore, aloin induced
      melanoma cell differentiation through the enhancement of melanogenesis and
      transglutaminase activity. To improve the growth-inhibiting effect of anticancer
      agents, we found that the combined treatment of cells with aloin and low doses of
      cisplatin increases the antiproliferative activity of aloin. The results suggest
      that aloin possesses antineoplastic and antimetastatic properties, exerted likely
      through the induction of melanoma cell differentiation.

PMID- 22139410
TI  - Effect of slow-release beta-alanine tablets on absorption kinetics and
      paresthesia.
AB  - Oral beta-alanine (betaA) doses larger than 800 mg commonly result in unpleasant
      sensory symptoms (paresthesia). However, the association of form (pure vs. slow
      release) with side-effects has not been fully described. The aim of this single
      blinded, randomized three-arm clinical trial was to compare plasma kinetics and
      symptoms following betaA bolus administration in solution or in slow-release
      tablet form. Eleven healthy adults ingested 1.6 g of a pure betaA reference
      solution (REF), 1.6 g in slow-release betaA tablets (TAB) or a placebo (PLA)
      after an overnight fast. During the next 6 h, urinary and plasma betaA
      concentrations were measured and questionnaires about intensity, nature (pins and
      needles, itching, flushing, irritation, numbness, soreness), and spatial
      distribution of unusual sensations were filled in. TAB resulted in a smaller peak
      plasma concentration than REF (82 vs. 248 MUmol L(-1), p<0.001), delayed time to
      peak (1.0 vs. 0.5 h, p<0.01) no difference in area under the curve, reduced loss
      in urine (202 vs. 663 MUmol, p<0.0001), and improved retention (98.9 vs. 96.3%,
      p<0.001). Symptoms described as "pins and needles" were perceived rapidly on the
      skin of the arms and trunk after REF (Tmax=15 min) and their time course nearly
      mimicked plasma concentrations. Maximum intensity scores were weaker with TAB
      ("very low") than with REF ("low", p<0.001), while TAB and PLA did not differ
      with respect to side-effects. In summary, ingesting 1.6 g betaA in slow-release
      tablets rather than pure in solution results in slower absorption kinetics,
      improved whole body retention and sensory side-effects that cannot be
      differentiated from PLA.

PMID- 22139411
TI  - Transglutaminase 2 as a biomarker of osteoarthritis: an update.
AB  - Osteoarthritis is a progressive joint disease characterized by cartilage
      degradation and bone remodelling. Under physiologic conditions, articular
      cartilage displays a stable chondrocyte phenotype, whereas in osteoarthritis a
      chondrocyte hypertrophy develops near the sites of cartilage surface damage and
      associates to the pathologic expression of type X collagen. Transglutaminases
      (TGs) include a family of Ca(2+)-dependent enzymes that catalyze the formation of
      gamma-glutamyl cross-links. Their substrates include a variety of intracellular
      and extracellular macromolecular components. TGs are ubiquitously and abundantly
      expressed and implicated in a variety of physiopathological processes. TGs
      activity is modulated by inflammatory cytokines. TG2 (also known as tissue
      transglutaminase) mediates the hypertrophic differentiation of joint chondrocytes
      and interleukin-1-induced calcification. Histomorphometrical and biomolecular
      investigations document increased TG2 expression in human and experimental
      osteoarthritis. Consequently, the level of TG2 expression may represent an
      adjuvant additional marker to monitor tissue remodelling occurring in
      osteoarthritic joint tissue. Experimental induction of osteoarthritis in TG2
      knockout mice is followed from reduced cartilage destruction and increased
      osteophyte formation compared to wild-type mice, suggesting a different influence
      on joint bone and cartilage remodelling. The capacity of transamidation by TG2 to
      regulate activation of latent TGF-beta seems to have a potential impact on the
      regulation of inflammatory response in osteoarthritic tissues. Additional studies
      are needed to define TG2-regulated pathways that are differently modulated in
      osteoblasts and chondrocytes during osteoarthritis.

PMID- 22139412
TI  - eIF5A isoforms and cancer: two brothers for two functions?
AB  - Eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein
      that contains the unusual amino acid hypusine [N(epsilon)-(4-amino-2
      hydroxybutyl)lysine]. The role of hypusine formation in the eIF5A protein in the
      regulation of cell proliferation and apoptosis is addressed in the present
      review. Moreover, vertebrates carry two genes that encode two eIF5A isoforms,
      eIF5A-1 and eIF5A-2, which, in humans, are 84% identical. However, the biological
      functions of these two isoforms may be significantly different. In fact, eIF5A-1
      is demonstrable in most cells of different histogenesis, whereas eIF5A-2 protein
      is detectable only in certain human cancer cells or tissues, suggesting its role
      as a potential oncogene. In this review we focus our attention on the involvement
      of eIF5A-1 in the triggering of an apoptotic program and in the regulation of
      cell proliferation. In addition, the potential oncogenic role and prognostic
      significance of eIF5A-2 in the prediction of the survival of cancer patients is
      described. eIF5A-1 and/or the eIF5A-2 isoform may serve as a new molecular
      diagnostic or prognostic marker or as a molecular target for anti-cancer therapy.

PMID- 22139414
TI  - Superhydrophobic gecko feet with high adhesive forces towards water and their bio
      inspired materials.
AB  - Functional integration is an inherent characteristic for multiscale structures of
      biological materials. In this contribution, we first investigate the liquid-solid
      adhesive forces between water droplets and superhydrophobic gecko feet using a
      high-sensitivity micro-electromechanical balance system. It was found, in
      addition to the well-known solid-solid adhesion, the gecko foot, with a
      multiscale structure, possesses both superhydrophobic functionality and a high
      adhesive force towards water. The origin of the high adhesive forces of gecko
      feet to water could be attributed to the high density nanopillars that contact
      the water. Inspired by this, polyimide films with gecko-like multiscale
      structures were constructed by using anodic aluminum oxide templates, exhibiting
      superhydrophobicity and a strong adhesive force towards water. The static water
      contact angle is larger than 150 degrees  and the adhesive force to water is
      about 66 MUN. The resultant gecko-inspired polyimide film can be used as a
      "mechanical hand" to snatch micro-liter liquids. We expect this work will provide
      the inspiration to reveal the mechanism of the high-adhesive superhydrophobic of
      geckos and extend the practical applications of polyimide materials.

PMID- 22139415
TI  - Combined therapy of voriconazole and anidulafungin in murine infections by
      Aspergillus flavus.
AB  - The efficacy of the combination of anidulafungin (AFG) at 1 mg/kg plus
      voriconazole (VRC) at 25 mg/kg was evaluated in a murine model of disseminated
      infection by Aspergillus flavus using three isolates previously tested in vitro.
      All the combinations showed indifferent in vitro interaction with the exception
      of one, which showed synergy. In general, the combined treatment prolonged the
      survival and reduced the fungal load in comparison with AFG alone, and only in a
      few cases, it improved the results of the VRC monotherapy. The combination of the
      two drugs and VRC alone reduced the galactomannan levels in serum in comparison
      with the control group.

PMID- 22139416
TI  - Inebriation, drinking motivations and sexual risk taking among sexually
      transmitted disease clinic patients in St. Petersburg, Russia.
AB  - We investigated whether inebriation was associated with having non-main partners
      and unprotected sex with non-main partners and whether drinking motivations were
      associated with sexual risk behaviors among patients attending an STD clinic in
      St Petersburg, Russia. A cross-sectional behavior survey was applied to 362
      participants between 2008 and 2009. Multivariate logistic regression was used for
      analysis. At-risk drinking per Alcohol Use Disorders Identification Test (AUDIT
      C) criteria (OR 2.5, 95% CI 1.4-4.4) was independently associated with having non
      main sexual partners. Inebriation (OR 3.2, 95% CI 1.3-8.1) but not at-risk
      drinking or drinking prior to sex was associated with unprotected sex with non
      main partners. Among drinkers, the consumption of alcohol to facilitate sexual
      encounters (OR 2.7, 95% CI 1.6-4.5) was associated with having non-main sexual
      partners. HIV prevention programs in Russia must address inebriation in addition
      to conventional patterns of problem drinking such as those measured by AUDIT-C
      and consider individuals' motivations to drink that lead to sexual risk taking.

PMID- 22139413
TI  - Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions.
AB  - Vasoactive intestinal peptide (VIP), a 28-amino acid
      neuropeptide/neurotransmitter, is widely distributed in both the central and
      peripheral nervous system. VIP is released by both neurons and immune cells.
      Various cell types, including immune cells, express VIP receptors. VIP has
      pleiotropic effects as a neurotransmitter, immune regulator, vasodilator and
      secretagogue. This review is focused on VIP production and effects on immune
      cells, VIP receptor signaling as related to immune functions, and the involvement
      of VIP in inflammatory and autoimmune disorders. The review addresses present
      clinical use of VIP and future therapeutic directions.

PMID- 22139417
TI  - A case of an aberrant internal carotid artery with a persistent stapedial artery:
      association of hypoplasia of the A1 segment of the anterior cerebral artery.
AB  - Congenital vascular variants involving the temporal bones are rare. Awareness of
      these variants is important as they may mimic glomus tumors or complicate middle
      ear surgery. We present a case of a persistent stapedial artery associated with
      an aberrant carotid artery in the left temporal bone, which is highlighted in
      computed tomography imaging findings. We further discuss a possible relationship
      between hypoplasia of the A1 segment of the anterior cerebral artery and this
      congenital variant.

PMID- 22139418
TI  - Atomic homodyne detection of continuous-variable entangled twin-atom states.
AB  - Historically, the completeness of quantum theory has been questioned using the
      concept of bipartite continuous-variable entanglement. The non-classical
      correlations (entanglement) between the two subsystems imply that the observables
      of one subsystem are determined by the measurement choice on the other,
      regardless of the distance between the subsystems. Nowadays, continuous-variable
      entanglement is regarded as an essential resource, allowing for quantum enhanced
      measurement resolution, the realization of quantum teleportation and quantum
      memories, or the demonstration of the Einstein-Podolsky-Rosen paradox. These
      applications rely on techniques to manipulate and detect coherences of quantum
      fields, the quadratures. Whereas in optics coherent homodyne detection of
      quadratures is a standard technique, for massive particles a corresponding method
      was missing. Here we report the realization of an atomic analogue to homodyne
      detection for the measurement of matter-wave quadratures. The application of this
      technique to a quantum state produced by spin-changing collisions in a Bose
      Einstein condensate reveals continuous-variable entanglement, as well as the twin
      atom character of the state. Our results provide a rare example of continuous
      variable entanglement of massive particles. The direct detection of atomic
      quadratures has applications not only in experimental quantum atom optics, but
      also for the measurement of fields in many-body systems of massive particles.

PMID- 22139420
TI  - Antibody-based protection against HIV infection by vectored immunoprophylaxis.
AB  - Despite tremendous efforts, development of an effective vaccine against human
      immunodeficiency virus (HIV) has proved an elusive goal. Recently, however,
      numerous antibodies have been identified that are capable of neutralizing most
      circulating HIV strains. These antibodies all exhibit an unusually high level of
      somatic mutation, presumably owing to extensive affinity maturation over the
      course of continuous exposure to an evolving antigen. Although substantial effort
      has focused on the design of immunogens capable of eliciting antibodies de novo
      that would target similar epitopes, it remains uncertain whether a conventional
      vaccine will be able to elicit analogues of the existing broadly neutralizing
      antibodies. As an alternative to immunization, vector-mediated gene transfer
      could be used to engineer secretion of the existing broadly neutralizing
      antibodies into the circulation. Here we describe a practical implementation of
      this approach, which we call vectored immunoprophylaxis (VIP), which in mice
      induces lifelong expression of these monoclonal antibodies at high concentrations
      from a single intramuscular injection. This is achieved using a specialized adeno
      associated virus vector optimized for the production of full-length antibody from
      muscle tissue. We show that humanized mice receiving VIP appear to be fully
      protected from HIV infection, even when challenged intravenously with very high
      doses of replication-competent virus. Our results suggest that successful
      translation of this approach to humans may produce effective prophylaxis against
      HIV.

PMID- 22139421
TI  - Frictional ageing from interfacial bonding and the origins of rate and state
      friction.
AB  - Earthquakes have long been recognized as being the result of stick-slip
      frictional instabilities. Over the past few decades, laboratory studies of rock
      friction have elucidated many aspects of tectonic fault zone processes and
      earthquake phenomena. Typically, the static friction of rocks grows
      logarithmically with time when they are held in stationary contact, but the
      mechanism responsible for this strengthening is not understood. This time
      dependent increase of frictional strength, or frictional ageing, is one
      manifestation of the 'evolution effect' in rate and state friction theory. A
      prevailing view is that the time dependence of rock friction results from
      increases in contact area caused by creep of contacting asperities. Here we
      present the results of atomic force microscopy experiments that instead show that
      frictional ageing arises from the formation of interfacial chemical bonds, and
      the large magnitude of ageing at the nanometre scale is quantitatively consistent
      with what is required to explain observations in macroscopic rock friction
      experiments. The relative magnitude of the evolution effect compared with that of
      the 'direct effect'--the dependence of friction on instantaneous changes in slip
      velocity--determine whether unstable slip, leading to earthquakes, is possible.
      Understanding the mechanism underlying the evolution effect would enable us to
      formulate physically based frictional constitutive laws, rather than the current
      empirically based 'laws', allowing more confident extrapolation to natural
      faults.

PMID- 22139419
TI  - New gene functions in megakaryopoiesis and platelet formation.
AB  - Platelets are the second most abundant cell type in blood and are essential for
      maintaining haemostasis. Their count and volume are tightly controlled within
      narrow physiological ranges, but there is only limited understanding of the
      molecular processes controlling both traits. Here we carried out a high-powered
      meta-analysis of genome-wide association studies (GWAS) in up to 66,867
      individuals of European ancestry, followed by extensive biological and functional
      assessment. We identified 68 genomic loci reliably associated with platelet count
      and volume mapping to established and putative novel regulators of
      megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific
      gene expression patterns and extensive network connectivity. Using gene silencing
      in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as
      novel regulators of blood cell formation. Taken together, our findings advance
      understanding of novel gene functions controlling fate-determining events during
      megakaryopoiesis and platelet formation, providing a new example of successful
      translation of GWAS to function.

PMID- 22139422
TI  - Modulation of TRPA1 thermal sensitivity enables sensory discrimination in
      Drosophila.
AB  - Discriminating among sensory stimuli is critical for animal survival. This
      discrimination is particularly essential when evaluating whether a stimulus is
      noxious or innocuous. From insects to humans, transient receptor potential (TRP)
      channels are key transducers of thermal, chemical and other sensory cues. Many
      TRPs are multimodal receptors that respond to diverse stimuli, but how animals
      distinguish sensory inputs activating the same TRP is largely unknown. Here we
      determine how stimuli activating Drosophila TRPA1 are discriminated. Although
      Drosophila TRPA1 responds to both noxious chemicals and innocuous warming, we
      find that TRPA1-expressing chemosensory neurons respond to chemicals but not
      warmth, a specificity conferred by a chemosensory-specific TRPA1 isoform with
      reduced thermosensitivity compared to the previously described isoform. At the
      molecular level, this reduction results from a unique region that robustly
      reduces the channel's thermosensitivity. Cell-type segregation of TRPA1 activity
      is critical: when the thermosensory isoform is expressed in chemosensors, flies
      respond to innocuous warming with regurgitation, a nocifensive response. TRPA1
      isoform diversity is conserved in malaria mosquitoes, indicating that similar
      mechanisms may allow discrimination of host-derived warmth--an attractant--from
      chemical repellents. These findings indicate that reducing thermosensitivity can
      be critical for TRP channel functional diversification, facilitating their use in
      contexts in which thermal sensitivity can be maladaptive.

PMID- 22139424
TI  - Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+
      channel.
AB  - High-conductance voltage- and Ca(2+)-activated K(+) channels function in many
      physiological processes that link cell membrane voltage and intracellular Ca(2+)
      concentration, including neuronal electrical activity, skeletal and smooth muscle
      contraction, and hair cell tuning. Like other voltage-dependent K(+) channels,
      Ca(2+)-activated K(+) channels open when the cell membrane depolarizes, but in
      contrast to other voltage-dependent K(+) channels, they also open when
      intracellular Ca(2+) concentrations rise. Channel opening by Ca(2+) is made
      possible by a structure called the gating ring, which is located in the
      cytoplasm. Recent structural studies have defined the Ca(2+)-free, closed,
      conformation of the gating ring, but the Ca(2+)-bound, open, conformation is not
      yet known. Here we present the Ca(2+)-bound conformation of the gating ring. This
      structure shows how one layer of the gating ring, in response to the binding of
      Ca(2+), opens like the petals of a flower. The degree to which it opens explains
      how Ca(2+) binding can open the transmembrane pore. These findings present a
      molecular basis for Ca(2+) activation of K(+) channels and suggest new
      possibilities for targeting the gating ring to treat conditions such as asthma
      and hypertension.

PMID- 22139426
TI  - Molecular imprinting for removing highly toxic organic pollutants.
AB  - Molecular imprinting technology allows synthesis of polymers with specific
      recognition ability towards target pollutants, which show potential to
      selectively remove Highly Toxic Organic Pollutants (HTOPs) in the presence of
      common organic matrices that are thousands of times more abundant than the
      targets. This feature article summarizes the current development of molecular
      imprinting for removing HTOPs from polluted water, with a special emphasis on the
      application of molecularly imprinted polymers to improve the efficiency of
      photocatalytic and biological degradation of HTOPs in wastewater.

PMID- 22139425
TI  - Increased miRNA-146a and miRNA-155 expressions in oral lichen planus.
AB  - Oral lichen planus (OLP) is a chronic inflammatory disease T helper 1 lymphocytes
      (Th1)-mediated. Interferon-gamma (IFN-gamma) plays a central role in local immune
      response in this disease. MicroRNAs (miRNAs) are endogenously expressed non
      coding RNAs that have important biological and pathological functions due to
      their potential mechanism regulating gene expression. Recently, some studies have
      demonstrated that miRNA-146a and miRNA-155 participate in immune response
      regulation, and are important in several chronic inflammatory and autoimmune
      diseases. The purpose of the present study was to investigate the expression of
      the miRNA-146a and miRNA-155 in 31 OLP lesions compared to normal oral mucosa and
      blood samples. Quantitative real-time polymerase chain reaction was used to
      analyze miRNA expressions. Our results showed increased expression of miRNA-146a
      and miRNA-155 in OLP lesions. In conclusion, these data highlight the possibility
      of miRNA-146a and miRNA-155 involvement in the regulation of the immune response
      in OLP.

PMID- 22139427
TI  - Cucurmosin induces apoptosis of BxPC-3 human pancreatic cancer cells via
      inactivation of the EGFR signaling pathway.
AB  - Pancreatic cancer remains the fourth most common cause of cancer-related death in
      the United States. Potent therapeutic strategies are urgently needed for
      pancreatic cancer. Cucurmosin is a novel type 1 ribosome-inactivating protein
      (RIP) isolated from the sarcocarp of Cucurbita moschata (pumpkin). Due to its
      cytotoxicity, cucurmosin can inhibit tumor cell proliferation through induction
      of apoptosis on tumor cells, but the specific mechanism is still unclear. We
      explored the function of cucurmosin in BxPC-3 pancreatic cancer cells using
      multiple cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay, flow cytometry, reverse transcription
      polymerase chain reaction (RT-PCR), Western blotting and transmission electron
      microscopy for observing typical changes and formation of apoptotic bodies. We
      found that cucurmosin inhibited the proliferation of BxPC-3 cells in a time- and
      dose-dependent manner, and increased the cell population in the G0-G1 phase. With
      increasing concentration of cucurmosin, the expression of EGFR, p-PI3K, Akt, p
      Akt, mTOR, p-mTOR, P70S6K-alpha, p-P70S6K-alpha, 4E-BP1 and p-4E-BP1 at the
      protein level was decreased, whereas the expression of p-Bad and caspase-9 was
      elevated. However, the mRNA expression of EGFR did not change. These findings
      suggest that cucurmosin can down-regulate the expression of EGFR by targeting.
      Cucurmosin induces the apoptosis of BxPC-3 pancreatic cancer cells via the
      PI3K/Akt/mTOR signaling pathway.

PMID- 22139428
TI  - Effects of low atmospheric CO2 and elevated temperature during growth on the gas
      exchange responses of C3, C3-C4 intermediate, and C4 species from three
      evolutionary lineages of C4 photosynthesis.
AB  - This study evaluates acclimation of photosynthesis and stomatal conductance in
      three evolutionary lineages of C(3), C(3)-C(4) intermediate, and C(4) species
      grown in the low CO(2) and hot conditions proposed to favo r the evolution of
      C(4) photosynthesis. Closely related C(3), C(3)-C(4), and C(4) species in the
      genera Flaveria, Heliotropium, and Alternanthera were grown near 380 and 180
      MUmol CO(2) mol(-1) air and day/night temperatures of 37/29 degrees C. Growth
      CO(2) had no effect on photosynthetic capacity or nitrogen allocation to Rubisco
      and electron transport in any of the species. There was also no effect of growth
      CO(2) on photosynthetic and stomatal responses to intercellular CO(2)
      concentration. These results demonstrate little ability to acclimate to low CO(2)
      growth conditions in closely related C(3) and C(3)-C(4) species, indicating that,
      during past episodes of low CO(2), individual C(3) plants had little ability to
      adjust their photosynthetic physiology to compensate for carbon starvation. This
      deficiency could have favored selection for more efficient modes of carbon
      assimilation, such as C(3)-C(4) intermediacy. The C(3)-C(4) species had
      approximately 50% greater rates of net CO(2) assimilation than the C(3) species
      when measured at the growth conditions of 180 MUmol mol(-1) and 37 degrees C,
      demonstrating the superiority of the C(3)-C(4) pathway in low atmospheric CO(2)
      and hot climates of recent geological time.

PMID- 22139429
TI  - Stable isotope analyses reveal individual variability in the trophic ecology of a
      top marine predator, the southern elephant seal.
AB  - Identifying individuals' foraging strategies is critical to understanding the
      ecology of a species, and can provide the means to predict possible ecological
      responses to environmental change. Our study combines stable isotope analysis and
      satellite telemetry to study the variability in individual foraging strategies of
      adult female southern elephant seals (Mirounga leonina). Our hypothesis is that
      female elephant seals from the Western Antarctica Peninsula (WAP) display
      individual specialization in their diets. We captured adult female elephant seals
      (n = 56, 2005-2009) at Livingston Island (Antarctica), and instrumented them with
      SMRU-CTD satellite tags. We collected blood, fur, and vibrissae samples for
      delta(13)C and delta(15)N analyses. The mean values for all vibrissae were -21.0
      +/- 0.70/00 for delta(13)C, and 10.4 +/- 0.80/00, for delta(15)N. The individual
      variability of delta(13)C (60%) was more important than the within-individual
      variability (40%) in explaining the total variance observed in our data. For
      delta(15)N, the results showed the opposite trend, with the within-individual
      variability (64%) contributing more to the total variance than the individual
      variability (36%), likely associated with the effect that the fasting periods
      have on delta(15)N values. Most individuals were specialists, as inferred from
      the low intra-individual variability of delta(13)C values with respect to the
      population variability, with half the individuals utilizing 31% or less of their
      available niche. We found eight different foraging strategies for these animals.
      Female elephant seals from the WAP are a diverse group of predators with
      individuals utilizing only a small portion of the total available niche, with the
      consequent potential to expand their foraging habits to exploit other resources
      or environments in the Southern Ocean.

PMID- 22139430
TI  - Plant species coexistence at local scale in temperate swamp forest: test of
      habitat heterogeneity hypothesis.
AB  - It has been suggested that a heterogeneous environment enhances species richness
      and allows for the coexistence of species. However, there is increasing evidence
      that environmental heterogeneity can have no effect or even a negative effect on
      plant species richness and plant coexistence at a local scale. We examined
      whether plant species richness increases with local heterogeneity in the water
      table depth, microtopography, pH and light availability in a swamp forest
      community at three local spatial scales (grain: 0.6, 1.2 and 11.4 m). We also
      used the variance partitioning approach to assess the relative contributions of
      niche-based and other spatial processes to species occurrence. We found that
      heterogeneity in microtopography and light availability positively correlated
      with species richness, in accordance with the habitat heterogeneity hypothesis.
      However, we recorded different heterogeneity-diversity relationships for
      particular functional species groups. An increase in the richness of bryophytes
      and woody plant species was generally related to habitat heterogeneity at all
      measured spatial scales, whereas a low impact on herbaceous species richness was
      recorded only at the 11.4 m scale. The distribution of herbaceous plants was
      primarily explained by other spatial processes, such as dispersal, in contrast to
      the occurrence of bryophytes, which was better explained by environmental
      factors. Our results suggest that both niche-based and other spatial processes
      are important determinants of the plant composition and species turnover at local
      spatial scales in swamp forests.

PMID- 22139431
TI  - Category formation in autism: can individuals with autism form categories and
      prototypes of dot patterns?
AB  - There is a growing amount of evidence suggesting that individuals with autism
      have difficulty with categorization. One basic cognitive ability that may
      underlie this difficulty is the ability to abstract a prototype. The current
      study examined prototype and category formation with dot patterns in high
      functioning adults with autism and matched controls. Individuals with autism were
      found to have difficulty forming prototypes and categories of dot patterns. The
      eye-tracking data did not reveal any between group differences in attention to
      the dot patterns. However, relationships between performance and intelligence in
      the autism group suggest possible processing differences between the groups.
      Results are consistent with previous studies that have found deficits in
      prototype formation and extend these deficits to dot patterns.

PMID- 22139432
TI  - Management of type IIb dyslipidemia.
AB  - Although the Japan Atherosclerosis Society guideline for the diagnosis and
      prevention of atherosclerosis cardiovascular diseases for the Japanese population
      provides targets for low-density lipoprotein (LDL) cholesterol, triglycerides,
      and high-density lipoprotein (HDL) cholesterol to prevent cardiovascular disease
      in patients with dyslipidemia, there is no guideline specifically targeting the
      treatment of type IIb dyslipidemia, which is one of the most common types of
      dyslipidemia, along with type IIa and type IV dyslipidemia. Type IIb dyslipidemia
      is important because it sometimes accompanies atherogenic lipid profiles, such as
      small, dense LDL, remnants, low HDL cholesterolemia. It is also associated with
      type 2 diabetes mellitus, metabolic syndrome, and chronic kidney disease (CKD),
      and most patients with familial combined hyperlipidemia (FCHL) show this
      phenotype; therefore, it is assumed that patients with type IIb dyslipidemia have
      a high risk for cardiovascular disease. Thus, the management of type IIb
      dyslipidemia is very important for the prevention of cardiovascular disease, so
      we have attempted to provide a guideline for the management of type IIb
      dyslipidemia.

PMID- 22139433
TI  - Euterpe oleracea (acai) modifies sterol metabolism and attenuates experimentally
      induced atherosclerosis.
AB  - AIM: Euterpe Oleracea (acai) is a fruit from the Amazon region whose chemical
      composition may be beneficial for individuals with atherosclerosis. We
      hypothesized that consumption of Euterpe Oleracea would reduce atherosclerosis
      development by decreasing cholesterol absorption and synthesis. METHODS: Male New
      Zealand rabbits were fed a cholesterol-enriched diet (0.5%) for 12 weeks, when
      they were randomized to receive Euterpe Oleracea extract (n = 15) or water (n =
      12) plus a 0.05% cholesterol-enriched diet for an additional 12 weeks. Plasma
      phytosterols and desmosterol were determined by ultra-performance liquid
      chromatography and mass spectrometry. Atherosclerotic lesions were estimated by
      computerized planimetry and histomorphometry. RESULTS: At sacrifice, animals
      treated with Euterpe Oleracea had lower levels of total cholesterol (p =0.03),
      non-HDL-cholesterol (p = 0.03) and triglycerides (p = 0.02) than controls. These
      animals had smaller atherosclerotic plaque area in their aortas (p = 0.001) and a
      smaller intima/media ratio (p = 0.002) than controls, without differences in
      plaque composition. At the end of the study, campesterol, beta-sitosterol, and
      desmosterol plasma levels did not differ between groups; however, animals treated
      with Euterpe Oleracea showed lower desmosterol/campesterol (p = 0.026) and
      desmosterol/ beta-sitosterol (p =0.006) ratios than controls. CONCLUSIONS:
      Consumption of Euterpe Oleracea extract markedly improved the lipid profile and
      attenuated atherosclerosis. These effects were related in part to a better
      balance in the synthesis and absorption of sterols.

PMID- 22139434
TI  - Pharmacological profile of ipragliflozin (ASP1941), a novel selective SGLT2
      inhibitor, in vitro and in vivo.
AB  - The pharmacological profile of ipragliflozin (ASP1941; (1S)-1,5-anhydro-1-C-{3
      [(1-benzothiophen-2-yl)methyl]-4-fluorophenyl}-D: -glucitol compound with L: 
      proline (1:1)), a novel SGLT2 selective inhibitor, was investigated. In vitro,
      the potency of ipragliflozin to inhibit SGLT2 and SGLT1 and stability were
      assessed. In vivo, the pharmacokinetic and pharmacologic profiles of
      ipragliflozin were investigated in normal mice, streptozotocin-induced type 1
      diabetic rats, and KK-A(y) type 2 diabetic mice. Ipragliflozin potently and
      selectively inhibited human, rat, and mouse SGLT2 at nanomolar ranges and
      exhibited stability against intestinal glucosidases. Ipragliflozin showed good
      pharmacokinetic properties following oral dosing, and dose-dependently increased
      urinary glucose excretion, which lasted for over 12 h in normal mice. Single
      administration of ipragliflozin resulted in dose-dependent and sustained
      antihyperglycemic effects in both diabetic models. In addition, once-daily
      ipragliflozin treatment over 4 weeks improved hyperglycemia with a concomitant
      increase in urinary glucose excretion in both diabetic models. In contrast,
      ipragliflozin at pharmacological doses did not affect normoglycemia, as was the
      case with glibenclamide, and did not influence intestinal glucose absorption and
      electrolyte balance. These results suggest that ipragliflozin is an orally active
      SGLT2 selective inhibitor that induces sustained increases in urinary glucose
      excretion by inhibiting renal glucose reabsorption, with subsequent
      antihyperglycemic effect and a low risk of hypoglycemia. Ipragliflozin has,
      therefore, the therapeutic potential to treat hyperglycemia in diabetes by
      increasing glucose excretion into urine.

PMID- 22139435
TI  - Carvacrol attenuates mechanical hypernociception and inflammatory response.
AB  - Carvacrol is a phenolic monoterpene present in the essential oil of the family
      Lamiaceae, as in the genera Origanum and Thymus. We previously reported that
      carvacrol is effective as an analgesic compound in various nociceptive models,
      probably by inhibition of peripheral mediators that could be related with its
      strong antioxidant effect observed in vitro. In this study, the anti
      hypernociceptive activity of carvacrol was tested in mice through models of
      mechanical hypernociception induced by carrageenan, and the involvement of
      important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF
      alpha), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also
      investigated the anti-inflammatory effect of carvacrol on the model of
      carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide
      (LPS)-induced nitrite production in murine macrophages was observed. Systemic
      pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of
      mechanical hypernociception and edema induced by carrageenan and TNF-alpha;
      however, no effect was observed on hypernociception induced by PGE(2) and
      dopamine. Besides this, carvacrol significantly decreased TNF-alpha levels in
      pleural lavage and suppressed the recruitment of leukocytes without altering the
      morphological profile of these cells. Carvacrol (1, 10, and 100 MUg/mL) also
      significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and
      did not produce citotoxicity in the murine peritoneal macrophages in vitro. The
      spontaneous locomotor activity of mice was not affected by carvacrol. This study
      adds information about the beneficial effects of carvacrol on mechanical
      hypernociception and inflammation. It also indicates that this monoterpene might
      be potentially interesting in the development of novel tools for management
      and/or treatment of painful conditions, including those related to inflammatory
      and prooxidant states.

PMID- 22139436
TI  - The pentosidine concentration in human blood specimens is affected by heating.
AB  - Pentosidine is an advanced glycation end product, formed by oxidation and
      glycation that accumulates markedly during end-stage renal failure. Measurement
      of the pentosidine level in physiological samples is applied as a sensitive
      marker for the early diagnosis of renal failure. In the quantitative measurements
      of pentosidine reported to date, a rapid enzyme-linked immunosorbent assay
      (ELISA) has been widely used to estimate the plasma/serum pentosidine levels in a
      number of clinical samples, because high performance liquid chromatography (HPLC)
      methods require multiple preparation steps before the analysis. However, the
      currently used clinical analysis of the plasma/serum pentosidine level by ELISA
      requires incubation of the plasma/serum at 100 degrees C for 15 min to inactivate
      the protease, which is required before the anti-pentosidine antibody can bind to
      the pentosidine. In the present study, we examined whether pentosidine could be
      generated artificially through the heating of serum. The pentosidine content,
      measured by HPLC, in the serum increased by heating in a temperature- and time
      dependent manner. The pentosidine content was increased 1.1- to 4.2-fold by the
      heating process compared to unheated samples, and the increased rate was not
      identical for each sample. After removing low-molecular weight (<10,000) serum
      components, the heat-induced pentosidine formation was decreased. Furthermore,
      the increase in pentosidine formation was significantly inhibited by acidic
      conditions more than by the addition of diethylene triamine pentaacetic acid, a
      metal chelator. This indicates that the level of serum pentosidine will be
      measured more accurately by ELISA if hydrochloric acid is added during the
      heating process.

PMID- 22139437
TI  - Conformationally pre-organized and pH-responsive flat dendrons: synthesis and
      self-assembly at the liquid-solid interface.
AB  - Efficient Cu-catalyzed 1,3-dipolar cycloaddition reactions have been used to
      prepare two series of three regioisomers of G-1 and G-2 poly(triazole-pyridine)
      dendrons. The G-1 and G-2 dendrons consist of branched yet conformationally pre
      organized 2,6-bis(phenyl/pyridyl-1,2,3-triazol-4-yl)pyridine (BPTP) monomeric and
      trimeric cores, respectively, carrying one focal and either two or four
      peripheral alkyl side chains. In the solid state, the conformation and
      supramolecular organization were studied by means of a single crystal X-ray
      structure analysis of one derivative. At the liquid-solid interface, the self
      assembly behavior was investigated by scanning tunneling microscopy (STM) on
      graphite surfaces. Based on the observed supramolecular organization, it appears
      that the subtle balance between conformational preferences inherent in the
      dendritic backbone on the one side and the adsorption and packing of the alkyl
      side chains on the graphite substrate on the other side dictate the overall
      structure formation in 2D.

PMID- 22139438
TI  - Genetic and environmental contributions to the association between anthropometric
      measures and iq: a study of Minnesota twins at age 11 and 17.
AB  - Associations of height and head circumference with IQ are well documented, but
      much less is known about the association of IQ with other anthropometric measures
      or the mechanisms behind these associations. We therefore analyzed the
      associations between IQ and several anthropometric measures using a twin-study
      design. Twins born in Minnesota were assessed at either age 11 (756 complete
      pairs) or 17 (626 complete pairs) and analyzed using genetic modeling. Head
      circumference and height showed the most consistent positive associations with
      IQ, whereas more detailed anthropometric measures were not significantly better
      predictors of IQ. These associations were mainly due to common genetic factors.
      Our results suggest that the same genetic factors have an effect on physical and
      cognitive development. Head circumference and height capture information on
      children's physical development, which is partly associated also with cognitive
      development.

PMID- 22139440
TI  - Fisetin inhibits various attributes of angiogenesis in vitro and in vivo-
      implications for angioprevention.
AB  - Studies have shown that fisetin, a small phytochemical molecule, has antitumor
      activity; however, its antiangiogenic activity has not yet been examined.
      Accordingly, herein, we investigated the antiangiogenic efficacy and associated
      mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin
      (10-50 MUM) strongly inhibited the regular serum plus growth supplement- and
      vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001)
      and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent
      manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M
      (moderate) phases together with a decrease in cyclin D1 and an increase in p53
      levels. Fisetin-caused cell death was accompanied by decreased expression of
      survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP
      ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore,
      fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P <
      0.001) as well as migration (up to 66%, P < 0.001), which were associated with
      decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in
      HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide
      synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells.
      In vivo matrigel plug assay in mice showed significant decrease in size (up to
      43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in
      the plugs from fisetin-treated, compared with control mice. Overall, these
      results suggest that fisetin inhibits various attributes of angiogenesis, which
      might contribute to its reported antitumor effects, and therefore, fisetin
      warrants further investigation for its angiopreventive potential toward cancer
      control.

PMID- 22139441
TI  - Quercetin-3-methyl ether suppresses proliferation of mouse epidermal JB6 P+ cells
      by targeting ERKs.
AB  - Chemoprevention has been acknowledged as an important and practical strategy for
      the management of skin cancer. Quercetin-3-methyl ether, a naturally occurring
      compound present in various plants, has potent anticancer-promoting activity. We
      identified this compound by in silico virtual screening of the Traditional
      Chinese Medicine Database using extracellular signal-regulated kinase 2 (ERK2) as
      the target protein. Here, we showed that quercetin-3-methyl ether inhibited
      proliferation of mouse skin epidermal JB6 P+ cells in a dose- and time-dependent
      manner by inducing cell cycle G(2)-M phase accumulation. It also suppressed 12-O
      tetradecanoylphorbol-13-acetate-induced neoplastic cell transformation in a dose
      dependent manner. Its inhibitory effect was greater than quercetin. The
      activation of activator protein-1 was dose-dependently suppressed by quercetin-3
      methyl ether treatment. Western blot and kinase assay data revealed that
      quercetin-3-methyl ether inhibited ERKs kinase activity and attenuated
      phosphorylation of ERKs. Pull-down assays revealed that quercetin-3-methyl ether
      directly binds with ERKs. Furthermore, a loss-of-function ERK2 mutation inhibited
      the effectiveness of the quercetin-3-methyl ether. Overall, these results
      indicated that quercetin-3-methyl ether exerts potent chemopreventive activity by
      targeting ERKs.

PMID- 22139442
TI  - Association between oral health and gastric precancerous lesions.
AB  - Although recent studies have suggested that tooth loss is positively related to
      the risk of gastric non-cardia cancer, the underlying oral health conditions
      potentially responsible for the association remain unknown. We investigated
      whether clinical and behavioral measures of oral health are associated with the
      risk of gastric precancerous lesions. We conducted a cross-sectional study of 131
      patients undergoing upper gastrointestinal endoscopy. Cases were defined as those
      with gastric precancerous lesions including intestinal metaplasia or chronic
      atrophic gastritis on the basis of standard biopsy review. A validated structured
      questionnaire was administered to obtain information on oral health behaviors. A
      comprehensive clinical oral health examination was performed on a subset of 91
      patients to evaluate for periodontal disease and dental caries experience. A
      total of 41 (31%) cases of gastric precancerous lesions were identified. Compared
      with non-cases, cases were significantly more likely to not floss their teeth
      [odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.09-7.64], adjusting for
      age, sex, race, body mass index, smoking status, educational attainment and
      Helicobacter pylori status in serum. Among participants who completed the oral
      examination, cases (n = 28) were more likely to have a higher percentage of sites
      with gingival bleeding than non-cases [OR = 2.63, 95% CI: 1.37-5.05 for a
      standard deviation increase in bleeding sites (equivalent to 19.7%)], independent
      of potential confounders. Our findings demonstrate that specific oral health
      conditions and behaviors such as gingival bleeding and tooth flossing are
      associated with gastric precancerous lesions.

PMID- 22139443
TI  - Differentiation-inducing factor-1 enhances 5-fluorouracil action on oral cancer
      cells inhibiting E2F1 and thymidylate synthase mRNAs accumulation.
AB  - PURPOSE: Differentiation-inducing factor-1 (DIF-1) is a morphogen originally
      identified in the amoebozoan Dictyostelium discoideum. In mammalian cells, it has
      been shown to activate GSK3beta, which in turn is expected to reduce levels of
      beta-catenin and cyclin D1, thus mediating DIF-1 antiproliferative properties.
      Since this could alter the expression and activity of E2F1 transcription factor
      and consequently those of the prognostic marker/chemotherapy target thymidylate
      synthase (TS), we evaluated (1) whether DIF-1 could effectively regulate these
      genes, (2) whether it could interfere with cell viability, and (3) whether DIF-1
      activity could enhance the efficacy of the TS inhibitor 5-fluorouracil (5-FU).
      METHODS: We investigated the effects of DIF-1 in continuous human cell lines
      derived from two oral tumor histotypes (corresponding to an adenosquamous and a
      squamous carcinoma) and a gingival epithelium. We evaluated mRNA accumulation by
      means of quantitative real-time PCR and efficacy of drugs on cell viability by
      means of MTT assay. RESULTS: DIF-1 inhibited the accumulation of E2F1 mRNA and
      reduces TS mRNA levels in tumor cell lines, but did not alter mRNA levels in the
      gingival counterpart. As a result, it inhibited proliferation preferentially of
      tumor cell in time- and concentration-dependent manner. Moreover, it enhanced
      cytotoxic effects of 5-FU only in tumor cell, whereas reduced them in the
      gingival counterpart. CONCLUSIONS: These findings suggest a tumor-specific action
      of DIF-1 on oral carcinoma cells. Thus, interfering with E2F1 and TS
      transcription, DIF-1 potentiates TS enzymatic inhibitors.

PMID- 22139444
TI  - microRNA-30c negatively regulates endometrial cancer cells by targeting
      metastasis-associated gene-1.
AB  - It is well known that microRNAs (miRNAs) play important roles in cancer
      development by targeting oncogenes or tumor-suppressor genes. However, little is
      known regarding the mechanisms of miR-30c action in endometrial cancer. In this
      study, we aimed to determine whether miR-30c targets metastasis-associated gene-1
      (MTA1) and acts as a tumor suppressor in endometrial cancer cell lines Ishikawa
      (estrogen receptor-positive, ER+) and HEC-1-B (ER-) by down-regulating MTA1. As a
      result, in both Ishikawa and HEC-1-B cells, real-time PCR demonstrated that
      overexpression of miR-30c led to the down-regulation of MTA1 mRNA (P<0.05), while
      Western blotting confirmed the reduced expression levels of MTA1 protein
      (P<0.01). A dual-luciferase reporter assay demonstrated that miR-30c was directly
      bound to the 3'-untranslated regions of MTA1. Then we studied the biological
      mechanisms of endometrial cancer cells transfected with the Pre-miR-30c plasmid.
      MTT assay and growth curves revealed that miR-30c inhibits both Ishikawa and HEC
      1-B cell proliferation. However, we did not see obvious differences in rates of
      apoptosis between miR-30c-overexpressing and the negative control cells. Then
      using wound-healing and Matrigel invasion assays, we found that the migratory and
      invasive abilities of cells transfected with the Pre-miR-30c plasmid were
      significantly suppressed compared with the control cells (P<0.01). Overall, our
      study, for the first time, showed that MTA1 is negatively regulated by miR-30c
      and that overexpression of miR-30c inhibits the proliferative, migratory and
      invasive abilities of endometrial cancer cells. These results suggest that miR
      30c acts as a tumor suppressor and negatively regulates endometrial cancer cells
      by targeting MTA1.

PMID- 22139445
TI  - Peripartum use of cell salvage: a university practice audit and literature
      review.
AB  - INTRODUCTION: Obstetrical hemorrhage is the second leading cause of direct
      maternal mortality (18% of maternal deaths) in developed countries and is the
      leading cause of severe maternal morbidity. The rising rate of obstetrical
      hemorrhage attributed to the repeated cesarean sections and invasive placental
      disorders, requiring blood transfusion has emphasized the need for alternatives
      to allogeneic blood donation. METHODS AND RESULTS: The Shaare Zedek Medical
      Center is a teaching hospital with the largest obstetric service in the region
      13,500 live births per year. The medical records of all parturients requiring use
      of intraoperative cell salvage system (IOCS) (2007-2011) were reviewed to
      evaluate our experience with this unique system and possible complications in the
      obstetrical milieu of a large obstetric unit. CONCLUSION: Using our combined
      medical records, we found that IOCS is a rapid method of blood replacement that
      allows blood bank service recruitment and presents no adverse reaction to the
      parturient. However, this sophisticated system is appropriate for tertiary
      surgical centers and its routine use should be assessed by national medical
      boards.

PMID- 22139446
TI  - Coenzyme Q10 content in follicular fluid and its relationship with oocyte
      fertilization and embryo grading.
AB  - BACKGROUND: No data are available on the presence and content of Coenzyme Q10
      (CoQ10) in human follicular fluid and its role. OBJECTIVE: To assess the presence
      and concentration of CoQ10 in human follicular fluid in relation to oocyte
      fertilization. METHODS: CQ10 content was measured in follicular fluid obtained
      from 20 infertile women undergoing ovarian stimulation program for in vitro
      fertilization. CoQ10 levels were assayed by high-performance liquid
      chromatography system and normalized for follicular cholesterol and protein
      levels. Oocyte morphology and embryo grading were assessed. RESULTS:
      CoQ10/Protein levels resulted significantly in mature versus dysmorphic oocytes.
      Similarly, CoQ10/Cholesterol was significantly higher in grading I-II versus
      grading III-IV embryos. CONCLUSIONS: This study is the first demonstration of the
      presence of CoQ10 in the human follicular fluid. Although the biological and
      endocrine mechanism of CoQ10 in the follicular fluid and its correlation with
      oocyte and embryo development is unclear, a new step may be the administration of
      CoQ10 in infertile women to evaluate the biological and reproductive outcomes.

PMID- 22139447
TI  - A facile reduction of Eu3+ to Eu2+ in gadolinium monosulfide nanoparticles using
      a mixed solvent of oleic acid/hexadecylamine.
AB  - We prepared GdS:Eu(3+) by simple thermal decomposition under 1-dodecanethiol. A
      reduction process was observed from Eu(3+) to Eu(2+) when oleic acid and
      hexadecylamine were injected into GdS:Eu(3+). Under UV excitation, GdS:Eu(3+)
      showed an intense orange-red emission and GdS:Eu(2+) showed a broad green band.

PMID- 22139448
TI  - Unrecognized visual field deficits in children with primary central nervous
      system brain tumors.
AB  - Visual field deficits can be a consequence of brain tumor location or treatment.
      The prevalence of unrecognized visual field deficits in children diagnosed with
      brain tumors is not known. All children at a single tertiary care pediatric
      children's hospital diagnosed with a primary brain tumor were tested for visual
      field deficits by a child neurologist and neuro-ophthalmologist over 16 months.
      Children with reproducible visual field deficits on two separate occasions were
      included in the analysis. Patients with optic glioma, craniopharyngioma, or
      previously known visual field deficits were excluded. Fourteen of 92 (15.2%)
      children (average 8.9 years, 8 girls) had undiagnosed visual field deficits.
      Average time between diagnosis of tumor and unrecognized visual field deficit was
      3.7 years (range 0-13 years). Unrecognized visual field deficits were not
      associated with age (P = 0.27) or gender (P = 0.38). Visual field deficits were
      attributed to direct tumor infiltration (n = 8), postoperative complications (n =
      5) and post-radiation edema (n = 1). Deficits included bitemporal hemianopsia (n
      = 2), homonymous hemianopsia (n = 9), quadrantanopsia (n = 2), and concentric
      visual field loss (n = 1.) Tumor location included temporal lobe (n = 9),
      parietal lobe (n = 2), posterior fossa (n = 2), hypothalamic-chiasmatic (n = 2)
      and multifocal areas (n = 4). Children with temporal lobe tumors were more likely
      to have unrecognized visual field deficits (P = 0.004). In all 14 patients,
      visual field deficits were determined by examination only and were not reported
      by either the patient or caregiver regardless of age. The prevalence of
      unrecognized visual field deficits in children with brain tumors can be
      surprisingly high. Serial neuro-ophthalmologic evaluation of children with brain
      tumors is often required to diagnose a visual field deficit since patient or
      caregiver reporting may be limited.

PMID- 22139449
TI  - Variability and directionality of temporal changes in delta(13)C and delta (15)N
      of aquatic invertebrate primary consumers.
AB  - Seasonal oscillations in the carbon (delta(13)C) and nitrogen (delta(15)N)
      isotope signatures of aquatic algae can cause seasonal enrichment-depletion
      cycles in the isotopic composition of planktonic invertebrates (e.g., copepods).
      Yet, there is growing evidence that seasonal enrichment-depletion cycles also
      occur in the isotope signatures of larger invertebrate consumers, taxa used to
      define reference points in isotope-based trophic models (e.g., trophic
      baselines). To evaluate the general assumption of temporal stability in non
      zooplankton aquatic invertebrates, delta(13)C and delta(15)N time series data
      from the literature were analyzed for seasonality and the influence of biotic
      (feeding group) and abiotic (trophic state, climate regime) factors on isotope
      temporal patterns. The amplitude of delta(13)C and delta(15)N enrichment
      depletion cycles was negatively related to body size, although all size-classes
      of invertebrates displayed a winter-to-summer enrichment in delta(13)C and
      depletion in delta(15)N. Among feeding groups, periphytic grazers were more
      variable and displayed larger temporal changes in delta(13)C than detritivores.
      For nitrogen, temporal variability and magnitude of directional change of
      delta(15)N was most strongly related to ecosystem trophic state (eutrophic >
      mesotrophic, oligotrophic). This study provides evidence of seasonality in the
      isotopic composition of aquatic invertebrates across very broad geographical and
      ecological gradients as well as identifying factors that are likely to modulate
      the strength and variability of seasonality. These results emphasize the need for
      researchers to recognize the likelihood of temporal changes in non-zooplankton
      aquatic invertebrate consumers at time scales relevant to seasonal studies and,
      if present, to account for temporal dynamics in isotope trophic models.

PMID- 22139450
TI  - The paradox of invasion in birds: competitive superiority or ecological
      opportunism?
AB  - Why can alien species succeed in environments to which they have had no
      opportunity to adapt and even become more abundant than many native species?
      Ecological theory suggests two main possible answers for this paradox:
      competitive superiority of exotic species over native species and opportunistic
      use of ecological opportunities derived from human activities. We tested these
      hypotheses in birds combining field observations and experiments along gradients
      of urbanization in New South Wales (Australia). Five exotic species attained
      densities in the study area comparable to those of the most abundant native
      species, and hence provided a case for the invasion paradox. The success of these
      alien birds was not primarily associated with a competitive superiority over
      native species: the most successful invaders were smaller and less aggressive
      than their main native competitors, and were generally excluded from artificially
      created food patches where competition was high. More importantly, exotic birds
      were primarily restricted to urban environments, where the diversity and
      abundance of native species were low. This finding agrees with previous studies
      and indicates that exotic and native species rarely interact in nature.
      Observations and experiments in the field revealed that the few native species
      that exploit the most urbanized environments tended to be opportunistic foragers,
      adaptations that should facilitate survival in places where disturbances by
      humans are frequent and natural vegetation has been replaced by man-made
      structures. Successful invaders also shared these features, suggesting that their
      success is not a paradox but can be explained by their capacity to exploit
      ecological opportunities that most native species rarely use.

PMID- 22139451
TI  - Pulse-reverse electrodeposition for mesoporous metal films: combination of
      hydrogen evolution assisted deposition and electrochemical dealloying.
AB  - Hydrogen evolution assisted electrodeposition is a new bottom-up technique
      allowing the fast and simple synthesis of nanometals. Electrochemical dealloying
      is a top-down approach with the same purpose. In this work, we show that a
      combination of these two methods in sequence by pulse-reverse electrodeposition
      can be used to prepare high-surface-area nanostructured metals. Highly porous
      adherent platinum is obtained by the deposition of CuPt alloy during the cathodic
      cycles and the selective dissolution of copper during the anodic cycles. The
      convection created by the movement of the hydrogen bubbles increases the
      deposition rate and removes the dissolved copper ions from the diffusion layer,
      which ensures the deposition of a film with the same stoichiometry throughout the
      whole process. Due to the relatively high ratio of copper atoms on the surface in
      the as-deposited layer, it is proposed that the dealloying kinetics is
      significantly higher than that usually observed during the dealloying process in
      a model system. The proposed approach has several advantages over other methods,
      such as a very high growth rate and needlessness of any post-treatment processes.
      A detailed analysis of the effect of pulse-reverse waveform parameters on the
      properties of the films is presented. Mesoporous platinum with pores and
      ligaments having characteristic sizes of less than 10 nm, an equivalent surface
      area of up to ca. 220 m(2) cm(-3), and a roughness factor of more than 1000 is
      fabricated.

PMID- 22139452
TI  - Impact of mGluR5 during amphetamine-induced hyperactivity and conditioned
      hyperactivity in differentially reared rats.
AB  - RATIONALE: 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride (MTEP) is
      a metabotropic glutamate receptor 5 (mGluR5) antagonist that may alter drug
      sensitivity in differentially reared rats due to its involvement in the
      psychostimulant reward pathway and plasticity. OBJECTIVES: The purpose of this
      study was to assess the effects of MTEP on acute amphetamine-induced
      hyperactivity, conditioned hyperactivity, and sensitization. METHODS: Rats were
      reared in an enriched (EC), isolated (IC), or standard (SC) condition after which
      rats were either administered MTEP (1.0 mg/kg, ip) or saline prior to an acute
      (0.5 or 1.0 mg/kg, sc) or repeated (0.3 mg/kg, sc) amphetamine exposure. Rats
      undergoing repeated amphetamine exposure were administered MTEP prior to
      conditioned hyperactivity and sensitization tests. RESULTS: EC and SC rats
      administered with MTEP prior to acute amphetamine demonstrated attenuated
      amphetamine-induced locomotor activity compared to controls, while IC rats
      administered MTEP following repeated amphetamine exposure demonstrated attenuated
      amphetamine-induced locomotor activity. Interestingly, MTEP treatment only
      altered conditioned hyperactivity in EC rats, as MTEP pretreatment resulted in
      conditioned hyperactivity in EC rats while conditioned hyperactivity was not
      observed in EC rats pretreated with saline. CONCLUSIONS: Glutamatergic pathways
      are altered during differential rearing, which differentially alters the role of
      mGluR5 in EC, IC, and SC rats when administered psychostimulant acutely versus
      repeatedly. These findings suggest that differential rearing alters glutamatergic
      function, which reduces sensitivity to psychostimulants.

PMID- 22139454
TI  - Marivita roseacus sp. nov., of the family Rhodobacteraceae, isolated from a
      temperate estuary and an emended description of the genus Marivita.
AB  - A gram-negative, non-motile, pigmented, rod-shaped and strictly aerobic bacterium
      (CB1052(T)) was isolated from a temperate estuary. On the basis of 16S rRNA gene
      sequence similarity, strain CB1052(T) belongs to the alpha-3 subclass of the
      Proteobacteria, within the family Rhodobacteraceae, having the highest similarity
      to members of the genus Marivita (97.8%) of the Roseobacter lineage. Pylogenetic
      analysis showed CB1052(T) to be a distinct sister clade to M. litorea and M.
      cryptomonadis and DNA-DNA relatedness was quite low amongst the strains (< 35%).
      Strain CB1052(T) cells are non-motile and display a needle-like filamentous form,
      where individual cells can become quite elongated (up to 15 MUm). Similar to M.
      litorea and M. cryptomonadis, CB1052(T) harbors aerobic anoxygenic photosynthesis
      genes. However, in contrast to other described Marivita species, strain CB1052(T)
      actively produces bacteriochlorophyll a. Further physiological features,
      including antibiotic sensitivities, differentiate strain CB1052(T) from the other
      members of the genus. Therefore, strain CB1052(T) is considered to represent a
      novel species of the genus Marivita, for which the name Marivita roseacus sp.
      nov. is proposed, with the type strain CB1052(T) (=DSM 23118(T) =ATCC BAA
      1914(T)).

PMID- 22139453
TI  - Behavioural and neuroinflammatory effects of the combination of binge ethanol and
      MDMA in mice.
AB  - RATIONALE: Binge drinking is a common pattern of alcohol consumption among young
      people. Binge drinkers are especially susceptible to brain damage when other
      substances are co-administered, in particular, 3,4-methylendioxymethamphetamine
      (MDMA). OBJECTIVE: To evaluate the behavioural consequences of voluntary binge
      ethanol consumption, alone and in combination to MDMA. Also, to elucidate the
      effects of the combined consumption of these two drugs on neuroinflammation.
      MATERIALS AND METHODS: Adolescent mice received MDMA (MDMA-treated mice), ethanol
      (ethanol-treated mice group) or both (ethanol plus MDMA-treated mice). Drinking
      in the dark (DID) procedure was used as a model of binge. Body temperature,
      locomotor activity, motor coordination, anxiety-like and despair behaviour in
      adolescent mice were evaluated 48 h, 72 h, and 7 days after the treatments. Also,
      neuroinflammatory response to these treatments was measured in the striatum.
      RESULTS: The hyperthermia observed in MDMA-treated mice was abolished by pre
      exposition to ethanol. Ethanol plus MDMA-treated mice showed lower locomotor
      activity. Ethanol-treated mice showed motor coordination impairment and increased
      despair behaviour. Anxiety-like behaviour was only seen in animals that were
      treated with both drugs. Contrarily, neuroinflammation was mostly seen in animals
      treated only with MDMA. CONCLUSIONS: Ethanol and MDMA co-administration increases
      the neurobehavioural changes induced by the consumption of each one of these
      drugs. However, as ethanol consumption did not increase neuroinflammatory
      responses induced by MDMA, other mechanisms, mediated by ethanol, are likely to
      account for this effect and need to be evaluated.

PMID- 22139455
TI  - The placement of South African strains of Beauveria in a phylogeny inferred from
      rDNA ITS1-5.8S-ITS2 sequences.
AB  - This study aimed to confirm the identity of three strains of the entomopathogenic
      fungus Beauveria bassiana from South African soils and to investigate their
      phylogenetic relationship with non-indigenous strains from other geographic
      regions. Sequences of the rDNA ITS1-5.8S-ITS2 region of 23 strains were compared
      with the Genbank reference sequences of 20 other cosmopolitan strains. Fitch
      parsimony and neighbor-joining analyses of the ITS1-5.8S-ITS2 regions resolved
      the strains into two distinct clades and matched them to four species
      groups/lineages: Beauveria bassiana, B. cf. bassiana (pseudobassiana), B.
      brongniartii and B. caledonica. Two of the South African strains initially
      identified as B. bassiana grouped with B. caledonica, whereas the third strain
      was confirmed as B. bassiana. Because of the paucity of Genbank references for B.
      caledonica, we have designated the two South African B. caledonica strains as B.
      sp. aff. caledonica. Other reassignments included two strains from Norway,
      originally classified as B. bassiana, being grouped with B. brongniartii, and
      three of the B. brongniartii reference taxa from Brazil which were clearly placed
      in the B. bassiana clade. The study provides a first report of the presence of
      the B. caledonica lineage in Africa and confirms current Beauveria phylogenies
      inferred from molecular data.

PMID- 22139456
TI  - Isolation and characterization of monochloroacetic acid-degrading bacteria.
AB  - Five Burkholderia strains (CL-1, CL-2, CL-3, CL-4, and CL-5) capable of degrading
      monochloroacetic acid (MCA) were isolated from activated sludge or soil samples
      gathered from several parts of Japan. All five isolates were able to grow on MCA
      as the sole source of carbon and energy, and argentometry and gas chromatography
      mass spectroscopy analyses showed that these five strains consumed MCA completely
      and released chloride ions stoichiometrically within 25 h. The five isolates also
      grew on monobromoacetic acid, monoiodoacetic acid, and L-2-monochloropropionic
      acid as sole sources of carbon and energy. In addition, the five isolates could
      not grow with DCA but dehalogenate single chlorine from DCA. Because PCR analyses
      revealed that all five isolates have an identical group II dehalogenase gene
      fragment and no group I deh gene, only strain CL-1 was analyzed further. The
      partial amino acid sequence of the group II dehalogenase of strain CL-1, named
      DehCL1, showed 74.6% and 65.2% identities to corresponding regions of the two MCA
      dehalogenases, DehCI from Pseudomonas sp. strain CBS-3 and Hdl IVa from
      Burkholderia cepacia strain MBA4, respectively. The secondary-structure motifs of
      the haloacid dehalogenase (HAD) superfamily and the amino acid residues involved
      in substrate binding, catalysis, and hydrophobic pocket formation were conserved
      in the partial amino acid sequence of DehCL1.

PMID- 22139457
TI  - Cryptococcus foliicola sp. nov. and Cryptococcus taibaiensis sp. nov., novel
      basidiomycetous yeast species from plant leaves.
AB  - A molecular taxonomic investigation performed on basidiomycetous yeast strains
      isolated from plant leaves collected in two areas of China revealed two novel
      species, Cryptococcus foliicola sp. nov. (type strain HS 23.3(T) = AS 2.2471(T) =
      CBS 9920(T)) and Cryptococcus taibaiensis sp. nov. (type strain ST 7.9(T) = AS
      2.2444(T) = CBS 9919(T)), among the non ballistoconidium-forming strains
      producing cream-colored colonies. These new species differed markedly from
      closely related species in the internal transcribed spacer (ITS) and 26S rRNA
      D1/D2 region sequences. They clustered in a strongly supported clade represented
      by Cryptococcus victoriae in the Tremellales group in the phylogenetic trees
      drawn from ITS and D1/D2 sequences.

PMID- 22139458
TI  - Gluconobacter uchimurae sp. nov., an acetic acid bacterium in the alpha
      Proteobacteria.

PMID- 22139459
TI  - A functional compound contained in sugar cane molasses enhances the fermentation
      ability of baker's yeast in high-sugar dough.

PMID- 22139460
TI  - Seasonal changes in the genetic diversity of two rodent populations, midday
      gerbil (Meriones meridianus) and northern three-toed jerboa (Dipus sagitta),
      detected by ISSR.
AB  - Seasonal changes in genetic diversity of Meriones meridianus and Dipus sagitta
      populations in the Ningxia Hui Autonomous Region were monitored using inter
      simple sequence repeats. There were 45 discernible DNA fragments isolated from 33
      samples of M. meridianus, and 25 from 40 samples of D. sagitta. The differences
      in gene frequencies are statistically significant for some alleles. Nei's index
      revealed that the greatest genetic differentiation was distributed within the
      seasonal groups. Nei's and Shannon's indexes exhibited similar seasonal trends,
      indicating that the spring group has the highest level of genetic diversity and
      that genetic diversity changes with the seasons. Correlation analysis found no
      statistically significant correlation between genetic diversity and population
      density. The results suggest that the seasonal changes in genetic diversity of
      the two species depend mainly on reproduction and dispersal.

PMID- 22139461
TI  - Oocyte morphology does not affect post-warming survival rate in an egg
      cryobanking donation program.
AB  - PURPOSE: To evaluate whether oocyte dysmorphisms affect oocyte survival rates in
      an egg-cryobanking donation program. METHODS: This study included 54 patients
      undergoing intracytoplasmic sperm injection. A total of 415 metaphase II oocytes
      were vitrified using the Cryotop method. Oocyte morphology was assessed
      immediately prior to oocyte vitrification under 400* magnification. The influence
      of dysmorphisms on post-thaw survival rates was assessed using regression
      analysis. Results were considered to be significant at the 5% critical level.
      RESULTS: Oocyte survival rate was not affected by the presence of the following
      analysed oocyte abnormalities: increased cytoplasmic granularity, vacuoles in the
      ooplasm, aggregates of smooth endoplasmic reticulum in the ooplasm, large
      perivitelline space size, perivitelline space granularity, fragmented first polar
      body and zona pellucida abnormalities. CONCLUSIONS: Oocyte morphology, observed
      prior to vitrification, does not predict post-warming survival. The non-invasive
      identification of predictive markers for oocyte survival potential remains a
      difficult task.

PMID- 22139462
TI  - Shear bond strength between an indirect composite layering material and
      feldspathic porcelain-coated zirconia ceramics.
AB  - OBJECTIVES: This study aims to evaluate the effect of both feldspathic porcelain
      coating of zirconia frameworks and priming agents on shear bond strength between
      an indirect composite material and zirconia frameworks. MATERIALS AND METHODS: A
      total of 462 airborne-particle-abraded zirconia disks were divided into three
      groups: untreated disks (ZR-AB), airborne-particle-abraded zirconia disks coated
      with feldspathic porcelain, (ZR-PO-AB), and hydrofluoric acid-etched zirconia
      disks coated with feldspathic porcelain (ZR-PO-HF). Indirect composite (Estenia
      C&B) was bonded to zirconia specimens with no (CON) or one of four priming agents
      -Clearfil Photo Bond (CPB), Clearfil Photo Bond with Clearfil Porcelain Bond
      Activator (CPB + activator), Estenia Opaque primer, or Porcelain Liner M Liquid B
      (PLB)--with or without an opaque material (Estenia C&B Opaque). All specimens
      were tested for shear bond strength before and after 20,000 thermocycles. The
      Steel-Dwass test and Mann-Whitney U test were used to compare shear bond
      strength. RESULTS: In ZR-AB specimens, the initial bond strength of the CPB and
      CPB + Activator groups was significantly higher as compared with the other three
      groups (P < 0.05), whereas the PLB and CPB + Activator groups had the highest pre
      and post-thermocycling bond strengths in ZR-PO-AB and ZR-PO-HF specimens. Among
      CON disks without opaque material, bond strength was significantly lower in ZR-AB
      specimens than in ZR-PO-AB and ZR-PO-HF specimens (P < 0.05). CONCLUSION:
      Feldspathic porcelain coating of a Katana zirconia framework enhanced the bond
      strength of Estenia C&B indirect composite to zirconia independent of surface
      treatment. The use of a silane coupling agent and opaque material yields durable
      bond strength between the indirect composite and feldspathic-porcelain-coated
      zirconia. CLINICAL RELEVANCE: The results of the present study suggest that
      feldspathic porcelain coating of zirconia frameworks is an effective method to
      obtain clinically acceptable bond strengths of a layering indirect composite
      material to a zirconia framework.

PMID- 22139463
TI  - Boundary lubrication by brushed salivary conditioning films and their degree of
      glycosylation.
AB  - OBJECTIVES: Toothbrushing, though aimed at biofilm removal, also affects the
      lubricative function of adsorbed salivary conditioning films (SCFs). Different
      modes of brushing (manual, powered, rotary-oscillatory or sonically driven)
      influence the SCF in different ways. Our objectives were to compare boundary
      lubrication of SCFs after different modes of brushing and to explain their
      lubrication on the basis of their roughness, dehydrated layer thickness, and
      degree of glycosylation. A pilot study was performed to relate in vitro
      lubrication with mouthfeel in human volunteers. MATERIALS AND METHODS:
      Coefficient of friction (COF) on 16-h-old SCFs after manual, rotary-oscillatory,
      and sonically driven brushing was measured using colloidal probe atomic force
      microscopy (AFM). AFM was also used to assess the roughness of SCFs prior to and
      after brushing. Dehydrated layer thicknesses and glycosylation of the SCFs were
      determined using X-ray photoelectron spectroscopy. Mouthfeel after manual and
      both modes of powered brushing were evaluated employing a split-mouth design.
      RESULTS: Compared with unbrushed and manually or sonically driven brushed SCFs,
      powered rotary-oscillatory brushing leads to deglycosylation of the SCF, loss of
      thickness, and a rougher film. Concurrently, the COF of a powered rotary
      oscillatory brushed SCF increased. Volunteers reported a slightly preferred
      mouthfeel after sonic brushing as compared to powered rotating-oscillating
      brushing. CONCLUSION: Deglycosylation and roughness increase the COF on SCFs.
      CLINICAL RELEVANCE: Powered rotary-oscillatory brushing can deglycosylate a SCF,
      leading to a rougher film surface as compared with manual and sonic brushing,
      decreasing the lubricative function of the SCF. This is consistent with clinical
      mouthfeel evaluation after different modes of brushing.

PMID- 22139464
TI  - Expression of ESBL-like activity in infrequently encountered members of the
      family Enterobacteriaceae.
AB  - A collection of 94 unusual members of the Enterobacteriaceae were screened for
      the presence of extended spectrum beta-lactamases (ESBLs) using the MicroScan
      ESbetaL plus dried confirmation panel. Presumptively positive strains were then
      confirmed for the presence of an ESBL by double disk diffusion, E-test strips (AB
      Biodisk, Solna, Sweden) and PCR for SHV, TEM, and CTX-M2 genes. Of the 18 strains
      initially positive on the ESbetaL panel only three strains (Leminorella
      grimontii, Klebsiella ozaenae, and Kluyvera ascorbata) were positive by
      confirmation methods. These results suggest laboratories should be cautious
      regarding the methodology employed in screening for the presence of ESBLs in
      enteric bacteria. However, it should be noted that of the 94 strains, 29 were
      found to be resistant to two or more of the antibiotics present in the MicroScan
      ESbetaL plus panel indicating that there are potential treatment issues with
      these organisms despite their lack of ESBLs.

PMID- 22139465
TI  - Fluoride-selective optical sensor based on the dipyrrolyl-tetrathiafulvalene
      chromophore.
AB  - A chemosensor bearing dipyrrolyl motifs as recognition sites and a
      tetrathiafulvalene redox tag has been evaluated as an optical and redox sensor
      for a series of anions (F(-), Cl(-), Br(-), HSO(4)(-), CH(3)COO(-), and
      H(2)PO(4)(-)) in DCM solution. The receptor shows specific optical signaling for
      fluoride but little electrochemical effect in solution. The solid-state
      performance of the sensor leads to measurable changes in water. Design
      implications towards better systems based on these results and other examples are
      discussed.

PMID- 22139466
TI  - SATe-II: very fast and accurate simultaneous estimation of multiple sequence
      alignments and phylogenetic trees.
AB  - Highly accurate estimation of phylogenetic trees for large data sets is
      difficult, in part because multiple sequence alignments must be accurate for
      phylogeny estimation methods to be accurate. Coestimation of alignments and trees
      has been attempted but currently only SATe estimates reasonably accurate trees
      and alignments for large data sets in practical time frames (Liu K., Raghavan S.,
      Nelesen S., Linder C.R., Warnow T. 2009b. Rapid and accurate large-scale
      coestimation of sequence alignments and phylogenetic trees. Science. 324:1561
      1564). Here, we present a modification to the original SATe algorithm that
      improves upon SATe (which we now call SATe-I) in terms of speed and of
      phylogenetic and alignment accuracy. SATe-II uses a different divide-and-conquer
      strategy than SATe-I and so produces smaller more closely related subsets than
      SATe-I; as a result, SATe-II produces more accurate alignments and trees, can
      analyze larger data sets, and runs more efficiently than SATe-I. Generally, SATe
      is a metamethod that takes an existing multiple sequence alignment method as an
      input parameter and boosts the quality of that alignment method. SATe-II-boosted
      alignment methods are significantly more accurate than their unboosted versions,
      and trees based upon these improved alignments are more accurate than trees based
      upon the original alignments. Because SATe-I used maximum likelihood (ML) methods
      that treat gaps as missing data to estimate trees and because we found a
      correlation between the quality of tree/alignment pairs and ML scores, we
      explored the degree to which SATe's performance depends on using ML with gaps
      treated as missing data to determine the best tree/alignment pair. We present two
      lines of evidence that using ML with gaps treated as missing data to optimize the
      alignment and tree produces very poor results. First, we show that the
      optimization problem where a set of unaligned DNA sequences is given and the
      output is the tree and alignment of those sequences that maximize likelihood
      under the Jukes-Cantor model is uninformative in the worst possible sense. For
      all inputs, all trees optimize the likelihood score. Second, we show that a
      greedy heuristic that uses GTR+Gamma ML to optimize the alignment and the tree
      can produce very poor alignments and trees. Therefore, the excellent performance
      of SATe-II and SATe-I is not because ML is used as an optimization criterion for
      choosing the best tree/alignment pair but rather due to the particular divide-and
      conquer realignment techniques employed.

PMID- 22139467
TI  - Tracheocutaneous fistula as a complication of laryngotracheal separation surgery.
AB  - To evaluate the relationship between the occurrence of tracheocutaneous fistula
      of the proximal tracheal stump regarding the indication (therapeutic or
      prophylactic) of laryngotracheal separation surgery (LTS) and regarding the
      presence of a current or previous tracheostomy when LTS was performed.
      Retrospective analysis of 66 patients submitted to LTS. The tracheocutaneous
      fistula occurred in 14 (21.2%) patients. Twelve (33.3%) of 36 patients whose
      indication was therapeutic and in two (6.7%) of 30 patients whose indication was
      prophylactic (p = 0.019). It occurred in 8 (57.1%) of 14 patients who had
      undergone tracheostomy prior to completion of LTS, while occurred in 6 (11.5%)
      patients who had not previously undergone tracheostomy (n = 52) (p = 0.0009). The
      incidence of tracheocutaneous fistula as a postoperative complication of
      laryngotracheal separation is high and occurs mainly in patients whose indication
      is therapeutic and for those with a current or previous tracheostomy. Despite the
      significant incidence, most of them closed spontaneously through the adoption of
      conservative therapy.

PMID- 22139468
TI  - Have two UK national guidelines had any effect on grommets day-case utilisation
      and rate over the last 10 years?
AB  - Grommets insertion is a common otolaryngological procedure for the treatment of
      persistent otitis media with effusion. In 2002, the Department of Health (DoH)
      Day Surgery guidelines stipulated that at least 75% of grommets insertions should
      be undertaken as day-cases. In 2008, after governmental perception of a higher
      than necessary grommet insertion rate, the National Institute for Health and
      Clinical Excellence (NICE) guidelines aimed at reducing inappropriate grommet
      insertions. This study analyses the effect these national interventions have had
      on grommets insertion in England and Wales. A retrospective study was undertaken.
      Data were extracted from the patient episode databases of England (Health Episode
      Statistics) and Wales (Patient Episode Database of Wales) from 2000 until 2010
      using OPCS-4 code D151. Statistical change in practice following the introduction
      of the interventions was assessed using linear regression. RESULTS: 341,526 and
      16,400 grommets insertions were performed in England and Wales, respectively.
      Linear regression analysis demonstrated that implementation of the Day Surgery
      guidelines significantly improved day-case rates in both national cohorts
      (England P < 0.0001, Wales P < 0.0001) and reduced mean waiting times for
      grommets insertion in both cohorts (England P < 0.05, Wales P < 0.01). Regression
      analysis also showed that implementation of the NICE guidelines had no effect on
      the number of grommet insertions in England (P > 0.5) and Wales (P > 0.5). In
      conclusion, the DoH guidelines have increased grommets day-case provision and
      reduced waiting times in both England and Wales, whereas the NICE guidelines have
      not affected overall levels of grommet insertion in either national cohort.

PMID- 22139469
TI  - Analysis of UV filters in tap water and other clean waters in Spain.
AB  - The present paper describes the development of a method for the simultaneous
      determination of five hormonally active UV filters namely benzophenone-3 (BP3), 3
      (4-methylbenzylidene) camphor (4MBC), 2-ethylhexyl 4-(dimethylamino) benzoate (OD
      PABA), 2-ethylhexyl 4-methoxycinnamate (EHMC) and octocrylene (OC) by means of
      solid-phase extraction and gas chromatography-electron impact ionization-mass
      spectrometry. Under optimized conditions, this methodology achieved low method
      limits of detection (needed for clean waters, especially drinking water
      analysis), between 0.02 and 8.42 ng/L, and quantitative recovery rates higher
      than 73% in all cases. Inter- and intraday precision for all compounds were lower
      than 7% and 11%, respectively. The optimized methodology was applied to perform
      the first survey of UV absorbing compounds in tap water from the metropolitan
      area and the city of Barcelona (Catalonia, Spain). In addition, other types of
      clean water matrices (mineral bottled water, well water and tap water treated
      with an ion-exchange resin) were investigated as well. Results evidenced that all
      the UV filters investigated were detected in the water samples analyzed. The
      compounds most frequently found were EHMC and OC. Maximum concentrations reached
      in tap water were 290 (BP3), 35 (4MBC), 110 (OD-PABA), 260 (EHMC), and 170 ng/L
      (OC). This study constitutes the first evidence of the presence of UV filter
      residues in tap water in Europe.

PMID- 22139470
TI  - Improved sample preparation for MALDI-MSI of endogenous compounds in skin tissue
      sections and mapping of exogenous active compounds subsequent to ex-vivo skin
      penetration.
AB  - Localization of endogenous and exogenous compounds directly in tissue sections is
      a challenging task in skin research. Matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry imaging (MSI) is a powerful label-free technique that
      enables determination of the distribution of a large range of biomolecules
      directly in tissue sections. Nevertheless, its application in this field is
      limited in large part by the low adhesion of skin tissue sections to indium-tin
      oxide-coated (ITO) glass slides. For the first time corona discharge (CD)
      treatment was used to modify the glass slide surface for improved adhesion.
      Localization of endogenous cholesterol sulfate was performed directly in human
      skin tissue sections. A spatial resolution of approximately 30 MUm was sufficient
      for assignment of mass signals to skin structure morphology. Furthermore, imaging
      of an exogenous model compound, Nile red, was performed directly in skin tissue
      sections after ex-vivo penetration into porcine skin, enabling determination of
      the pathway and depth of penetration. Finally, the ion density map of Nile red
      was compared with its high resolution fluorescence micrograph. This work provides
      new insights into the application of MALDI-MSI in skin research.

PMID- 22139471
TI  - Analysis of a stochastic predator-prey model with applications to intrahost HIV
      genetic diversity.
AB  - During an infection, HIV experiences strong selection by immune system T cells.
      Recent experimental work has shown that MHC escape mutations form an important
      pathway for HIV to avoid such selection. In this paper, we study a model of MHC
      escape mutation. The model is a predator-prey model with two prey, composed of
      two HIV variants, and one predator, the immune system CD8 cells. We assume that
      one HIV variant is visible to CD8 cells and one is not. The model takes the form
      of a system of stochastic differential equations. Motivated by well-known results
      concerning the short life-cycle of HIV intrahost, we assume that HIV population
      dynamics occur on a faster time scale then CD8 population dynamics. This
      separation of time scales allows us to analyze our model using an asymptotic
      approach. Using this model we study the impact of an MHC escape mutation on the
      population dynamics and genetic evolution of the intrahost HIV population. From
      the perspective of population dynamics, we show that the competition between the
      visible and invisible HIV variants can reach steady states in which either a
      single variant exists or in which coexistence occurs depending on the parameter
      regime. We show that in some parameter regimes the end state of the system is
      stochastic. From a genetics perspective, we study the impact of the population
      dynamics on the lineages of an HIV sample taken after an escape mutation occurs.
      We show that the lineages go through severe bottlenecks and that in certain
      parameter regimes the lineage distribution can be characterized by a Kingman
      coalescent. Our results depend on methods from diffusion theory and coalescent
      theory.

PMID- 22139472
TI  - The 'Butterfly effect' in Cayley graphs with applications to genomics.
AB  - Suppose a finite set X is repeatedly transformed by a sequence of permutations of
      a certain type acting on an initial element x to produce a final state y. For
      example, in genomics applications, X could be a set of genomes and the
      permutations certain genome 'rearrangements' or, in group theory, X could be the
      set of configurations of a Rubik's cube and the permutations certain specified
      moves. We investigate how 'different' the resulting state y' to y can be if a
      slight change is made to the sequence, either by deleting one permutation, or
      replacing it with another. Here the 'difference' between y and y' might be
      measured by the minimum number of permutations of the permitted type required to
      transform y to y', or by some other metric. We discuss this first in the general
      setting of sensitivity to perturbation of walks in Cayley graphs of groups with a
      specified set of generators. We then investigate some permutation groups and
      generators arising in computational genomics, and the statistical implications of
      the findings.

PMID- 22139473
TI  - Co-immobilization of three cellulases on Au-doped magnetic silica nanoparticles
      for the degradation of cellulose.
AB  - Three cystein-tagged cellulases co-immobilized on AuNP and Au-MSNP for the
      hydrolytic degradation of cellulose. The biochemical properties, stabilities,
      activities and reusability of these co-immobilized systems were compared to those
      of mixtures of free cellulases.

PMID- 22139474
TI  - If we designed airplanes like we design drugs....
AB  - In the early days, airplanes were put together with parts designed for other
      purposes (bicycles, farm equipment, textiles, automotive equipment, etc.). They
      were then flown by their brave designers to see if the design would work--often
      with disastrous results. Today, airplanes, helicopters, missiles, and rockets are
      designed in computers in a process that involves iterating through enormous
      numbers of designs before anything is made. Until very recently, novel drug-like
      molecules were nearly always made first like early airplanes, then tested to see
      if they were any good (although usually not on the brave scientists who created
      them!). The resulting extremely high failure rate is legendary. This article
      describes some of the evolution of computer-based design in the aerospace
      industry and compares it with the progress made to date in computer-aided drug
      design. Software development for pharmaceutical research has been largely
      entrepreneurial, with only relatively limited support from government and
      industry end-user organizations. The pharmaceutical industry is still about 30
      years behind aerospace and other industries in fully recognizing the value of
      simulation and modeling and funding the development of the tools needed to catch
      up.

PMID- 22139475
TI  - Evaluating the applicability domain in the case of classification predictive
      models for carcinogenicity based on the counter propagation artificial neural
      network.
AB  - The applicability domain (AD) of models developed for regulatory use has attached
      great attention recently. The AD of quantitative structure-activity relationship
      (QSAR) models is the response and chemical structure space in which the model
      makes predictions with a given reliability. The evaluation of AD of regressions
      QSAR models for congeneric sets of chemicals can be find in many papers and books
      while the issue about metrics for the evaluation of an AD for the non-linear
      models (like neural networks) for the diverse set of chemicals represents the new
      field of investigations in QSAR studies. The scientific society is standing
      before the challenge to find out reliable way for the evaluation of an AD of non
      linear models. The new metrics for the evaluation of the AD of the counter
      propagation artificial neural network (CP ANN) models are discussed in the
      article: the Euclidean distances between an object (molecule) and the
      corresponding excited neuron of the neural network and between an object
      (molecule) and the representative object (vector of average values of
      descriptors). The investigation of the training and test sets chemicals coverage
      in the descriptors space was made with the respect to false predicted chemicals.
      The leverage approach was used to compare non linear (CP ANN) models with linear
      ones.

PMID- 22139476
TI  - Some findings relevant to the mechanistic interpretation in the case of
      predictive models for carcinogenicity based on the counter propagation artificial
      neural network.
AB  - The goal of the study was to contribute to a better mechanistic understanding of
      so-called "general" QSAR models for non-congeneric chemicals based on the counter
      propagation artificial neural network (CP ANN). Possible mechanisms of action was
      proofed using the Toxtree expert system based on structural alerts (SAs) for
      carcinogenicity. We have illustrated how statistically selected MDL descriptors,
      which refer to topological characteristics as well as to polarizability and
      charge distribution related to reactivity, are correlated with particular
      chemical classes (containing carcinogenic SA) with the recognized mechanistic
      link to the carcinogenic activity and consequently with the carcinogenic potency.
      Mechanistic insight in CP ANN models was demonstrated using an inherent mapping
      technique (i.e. Kohonen maps).

PMID- 22139477
TI  - Protein kinase C mediated pH(i)-regulation of ROMK1 channels via a
      phosphatidylinositol-4,5-bisphosphate-dependent mechanism.
AB  - The protein kinase C (PKC) pathway is important for the regulation of K(+)
      transport. The renal outer medullar K(+) (ROMK1) channels show an exquisite
      sensitivity to intracellular protons (pH(i)) (effective pK(a) approximately 6.8)
      and play a key role in K(+) homeostasis during metabolic acidosis. Our molecular
      dynamic simulation results suggest that PKC-mediated phosphorylation on Thr-193
      may disrupt the PIP(2)-channel interaction via a charge-charge interaction
      between Thr-193 and Arg-188. Therefore, we investigated the role of PKC and pH(i)
      in regulation of ROMK1 channel activity using a giant patch clamp with Xenopus
      oocytes expressing wild-type and mutant ROMK1 channels. ROMK1 channels pre
      incubated with the PKC activator phorbol-12-myristate-13-acetate exhibited
      increased sensitivity to pH(i) (effective pK(a) shifted to pH approximately 7.0).
      In the presence of GF109203X--a PKC selective inhibitor--the effective pK(a) for
      inhibition of ROMK1 channels by pH(i) decreased (effective pK(a) shifted to pH
      approximately 6.5). The pH(i) sensitivity of ROMK1 channels mediated by PKC
      appeared to be dependent of PIP(2) depletion. The giant patch clamp together with
      site direct mutagenesis revealed that Thr-193 is the phosphorylation site on PKC
      that regulates the pH(i) sensitivity of ROMK1 channels. Mutation of PKC-induced
      phosphorylation sites (T193A) decreases the pH(i) sensitivity and increases the
      interaction of channel-PIP(2). Taken together, these results provide new insights
      into the molecular mechanisms underlying the pH(i) gating of ROMK1 channel
      regulation by PKC.

PMID- 22139478
TI  - A (U)MP2(full) and (U)CCSD(T) theoretical investigation into the substituent
      effects on the intermolecular T-shaped F-H...pi interactions between HF and LBBL
      (L = -H, : CO, :NN, -Cl, -CN and -NC).
AB  - The substituent effects on the intermolecular T-shaped F-H...pi interactions are
      investigated between HF and LBBL (L = -H, : CO, :NN, -Cl, -CN and -NC) using the
      (U)MP2(full) and (U)CCSD(T) methods with the 6-311++G(2 d,p) basis set. The B = B
      triple-bond contraction is found in the complexes with lone-pair-electron donors
      while the B = B double-bond is lengthened in the systems with the single-electron
      substituents upon complexation. The T-shaped F-H...pi interaction energies follow
      the order of ClB = BCl...HF>HB = BH...HF>NNB = BNN...HF>OCB = BCO...HF>CNB =
      BNC...HF>NCB = BCN...HF. The electron-donating substituents : CO and :NN
      increases electron density of the B = B triple bond by the delocalization
      interaction E ((2)) pi ((CO/NN) -> Lp(B)) while the electron-withdrawing
      substituents -CN and -NC decrease electron density of the B = B double bond by
      means of the pi-pi conjugative effect. The analyses of the APT atomic charge,
      "truncated" model, natural bond orbital (NBO), atoms in molecules (AIM) and
      electron density shifts reveal the nature of the substituent effect and explain
      the origin of the B = B bond contraction.

PMID- 22139479
TI  - Molecular simulation of a series of benzothiazole PI3Kalpha inhibitors: probing
      the relationship between structural features, anti-tumor potency and selectivity.
AB  - The phosphatidylinositol 3-kinase alpha (PI3Kalpha) was genetically validated as
      a promising therapeutic target for developing novel anticancer drugs. In order to
      explore the structure-activity correlation of benzothiazole series as inhibitors
      of PI3Kalpha, comparative molecular field analysis (CoMFA), comparative molecular
      similarity indices analysis (CoMSIA) were performed on 61 promising molecules to
      build 3D-QSAR models based on both the ligand- and receptor-based methods. The
      best CoMFA and CoMSIA models had a cross-validated coefficient r(cv)(2) of 0.618
      and 0.621, predicted correlation coefficient r(pred) (2) of 0.812 and 0.83,
      respectively, proving their high correlative and predictive abilities on both the
      training and test sets. In addition, docking analysis and molecular dynamics
      simulation (MD) were also applied to elucidate the probable binding modes of
      these inhibitors at the ATP binding pocket. Based on the contour maps and MD
      results, some key structural factors responsible for the activity of this series
      of compounds were revealed as follows: (1) Ring-A has a strong preference for
      bulky hydrophobic or aromatic groups; (2) Electron-withdrawing groups at the para
      position of ring-B and hydrophilic substituents in ring-B region may benefit the
      potency; (3) A polar substituent like -NHSO(2)- between ring-A and ring-B can
      enhance the activity of the drug by providing hydrogen bonding interaction with
      the protein target. The satisfactory results obtained from this work strongly
      suggest that the developed 3D-QSAR models and the obtained PI3Kalpha inhibitor
      binding structures are reasonable for the prediction of the activity of new
      inhibitors and be helpful in future PI3Kalpha inhibitor design.

PMID- 22139481
TI  - Real-time fluid dynamics investigation and physiological response for
      erythromycin fermentation scale-up from 50 L to 132 m3 fermenter.
AB  - The physiological response of erythromycin fermentation scale-up from 50 L to 132
      m(3) scale was investigated. A relatively high oxygen uptake rate (OUR) in early
      phase of fermentation was beneficial for erythromycin biosynthesis.
      Correspondingly, the maximal consistency coefficient (K) reflecting non-Newtonian
      fluid characteristics in 50 L and 132 m(3) fermenter also appeared in same phase.
      Fluid dynamics in different scale bioreactor was further investigated by real
      time computational fluid dynamics modeling. The results of simulation showed that
      the impeller combination in 50 L fermenter could provide more modest flow field
      environment compared with that in 132 m(3) fermenter. The decrease of oxygen
      transfer rate (OTR) in 132 m(3) fermenter was the main cause for impairing cell
      physiological metabolism and erythromycin biosynthesis. These results were
      helpful for understanding the relationship between hydrodynamic environment and
      physiological response of cells in bioreactor during the scale-up of fermentation
      process.

PMID- 22139480
TI  - Large-scale virtual screening for the identification of new Helicobacter pylori
      urease inhibitor scaffolds.
AB  - Here, we report a structure-based virtual screening of the ZINC database
      (containing about five million compounds) by computational docking and the
      analysis of docking energy calculations followed by in vitro screening against H.
      pylori urease enzyme. One of the compounds selected showed urease inhibition in
      the low micromolar range. Barbituric acid and compounds 1a, 1d, 1e, 1f, 1g, 1h
      were found to be more potent urease inhibitors than the standard inhibitor
      hydroxyurea, yielding IC(50) values of 41.6, 83.3, 66.6, 50, 58.8, and 60 MUM,
      respectively (IC(50) of hydroxyurea = 100 MUM). 5-Benzylidene barbituric acid has
      enhanced biological activities compared to barbituric acid. Furthermore, the
      results indicated that among the substituted 5-benzylidene barbiturates, those
      with para substitution have higher urease inhibitor activities. This may be
      because the barbituric acid moiety is closer to the bimetallic nickel center in
      unsubstituted or para-substituted than in ortho- or meta-substituted analogs, so
      it has greater chelating ability.

PMID- 22139483
TI  - [Recent advances in genetic research of inflammatory bowel disease].

PMID- 22139482
TI  - Reversal of postischemic hypoperfusion by tempol: endothelial signal transduction
      mechanism.
AB  - This report entails in vivo and in vitro studies concerned with free radical
      species involved in brain ischemia. The participation of reactive oxygen species
      (ROS) and reactive nitrogen species (RNS) in the early manifestation of cerebral
      ischemia/reperfusion was investigated in gerbils exposed to transient global
      ischemia using 4-OH-2,2,6,6-tetramethylpiperidine-1-oxyl (TPL), a well-known
      antioxidant. TPL treatment reversed cerebral postischemic hypoperfusion and
      tissue edema in these animals. The findings are consistent with ROS/RNS
      participation in tissue injury and the reduction of cerebromicrovascular blood
      flow (CBF) during postischemic recirculation. The activation/deactivation of
      signal transduction pathway by oxidation/antioxidation [i.e., using hydrogen
      peroxide (H2O2)/TPL] was evaluated in cultured human brain endothelial cells
      (HBEC) to assess the involvement of endothelial-dependent mechanisms. The data
      showed that H2O2 activates various "stress" kinases and vasodilalator-stimulated
      phosphoprotein (VASP); activation of this pathway was reduced by inhibitors of
      Rho- or IP-3 kinases, as well as TPL. H2O2 also induced cytoskeleton (actin)
      rearrangements in HBEC; this effect was prevented by inhibitors of Rho/IP3 kinase
      or TPL. The observed activation/deactivation of H2O2-induced "stress" kinase is
      in agreement with the reported capacity of ROS/RNS to stimulate the oxidative
      signal transduction pathway. The noted TPL reduction of H2O2-induced
      phosphorylation of kinase strongly suggests that the beneficial effect of TPL
      implicates the stress signal transduction pathway. This may represent a mechanism
      for the cerebral postischemic manifestations observed by in vivo experiments.

PMID- 22139484
TI  - [The new treatment of intractable ulcerative colitis].

PMID- 22139485
TI  - [The management of ulcerative colitis in remission stage and the strategies for
      colorectal cancer surveillance in ulcerative colitis].

PMID- 22139486
TI  - [Long-term function and quality of life after surgical treatments for ulcerative
      colitis - multicenter analysis for surgical patients with more than 5 years
      follow up].

PMID- 22139487
TI  - [Gemcitabine plus S-1 combination therapy (GS therapy) for pancreatic cancer
      patients with high-grade hepatic metastasis].
AB  - Pancreatic cancer shows the worst prognosis among the solid tumors, and survival
      for patients with high-grade liver metastasis is estimated at around a few
      months. We reported the effects of combination therapy with gemcitabine and S-1
      (GS therapy) on pancreatic cancer patients with high-grade hepatic metastasis.
      Patients with severe metastatic pancreatic cancer received chemotherapy
      comprising S-1 (30mg/m2 p.o. b.i.d., days 1-14) and gemcitabine (1000mg/m2 on
      days 1 and 8), repeated every 3 weeks. Fourteen patients (7 men, 7 women)
      received treatment at a mean age of 56.5 years (range, 39-76 years), achieving
      complete response in 1 patient, partial response in 5 patients, and stable
      disease in 3 patients and progressive disease in 5 patients. The response rate
      was thus 43%. Median progression-free survival was 186 days (95% confidence
      interval, 40-247 days). Median overall survival was 261 days (95% confidence
      interval, 162-358 days). GS therapy appears to be well-tolerated and effective in
      patients with high-grade hepatic metastasis.

PMID- 22139488
TI  - [A case of eosinophilic gastroenteritis with ring-like discoloration in the lower
      end of the esophagus].
AB  - We report the case of a 15-year-old Japanese boy with eosinophilic
      gastroenteritis. The patient complained of abdominal pain and watery diarrhea and
      had a history of allergic rhinitis. Laboratory data on admission showed
      leukocytosis with remarkable eosinophilia. Microscopic examination of the
      biopsied specimens taken from the esophagus, stomach, duodenum, lower ileum and
      colon showed eosinophilic infiltration. Especially in the lower esophagus, there
      was a ring-like discoloration with remarkable eosinophil infiltration. We
      diagnosed eosinophilic gastroenteritis and his clinical symptoms and eosinophilia
      improved following starting corticosteroid therapy. After 5 months therapy with
      prednisolone, discoloration of upper digestive tract disappeared. There have been
      no reports describing discoloration in the lower end of the esophagus seen by
      gastroscopy.

PMID- 22139489
TI  - [Advanced poorly differentiated adenocarcinoma of the colon with micropapillary
      carcinoma components except specific cytokeratin expressions, report of a case].
AB  - A 53-year-old woman had a tumor in the ascending colon. CT revealed tumor
      invasion to the surrounding tissue and also showed multiple swollen lymph nodes,
      liver metastases and ascites. Colonic tumor with severe stenosis was diagnosed by
      colonoscopy and the obtained biopsy specimen revealed poorly differentiated
      adenocarcinoma. Immunohistochemically, the tumor was positive for CEA, CK7, MUC2,
      MUC5AC.MUC6 (spotty) and negative for CK20, CDX2, TTF-1, GCDFP-15. Cytology of
      ascites also showed malignant cells. Although these protein expressions were
      specific for not primary colonic cancer but metastasis from ovarian cancer, the
      case was clinically and pathologically diagnosed as poorly differentiated
      adenocarcinoma of the colon with peritoneal metastases composed of micropapillary
      carcinoma. MLH1 and MSH2 protein expressions were normal. Even though modified
      FOLFOX6 chemotherapy was administered, the patient rapidly worsened due to
      pulmonary carcinomatous lymphangiosis and died a month after diagnosis. To
      determine the high-risk group of metastases, it seems necessary to require the
      accumulation of further cases evaluated by a precise immunohistochemistrical
      approach.

PMID- 22139490
TI  - [A case of cystic duct metastasis from rectal cancer].
AB  - A 67-year-old man underwent laparoscopic low anterior resection and open medial
      segmentectomy of the liver for rectal cancer and liver metastasis. During the
      operation, a cystic duct mass, 1cm in diameter, was found. Therefore
      cholecystectomy with partial resection of the common bile duct was also
      performed. The rectal tumor and liver tumor were diagnosed pathologically as
      moderately differentiated adenocarcinoma. The cystic duct mass was mainly located
      in the lamina propria and its histological aspects were similar to the rectal
      cancer. Immunohistochemical staining revealed that rectal, hepatic, and cystic
      duct lesions were all negative for CK7 but were all positive for CK20. These
      findings confirmed the diagnosis of rectal cancer with metastases to the liver
      and the cystic duct. Metastatic cystic duct tumor is extremely rare and has never
      been reported in the Japanese literature.

PMID- 22139491
TI  - [A case of rectal implantation cyst diagnosed by EUS and EUS-guided FNA].
AB  - A 73-year-old woman was referred to our hospital complaining of bloody stool. She
      had undergone high anterior resection with the double stapling technique for a
      sigmoid colon cancer 2 years prior to this admission. Colonoscopy revealed a soft
      submucosal tumor, 4cm in size, on the anal side of the previous anastomosis in
      the rectum. EUS revealed a cystic lesion located in the third and fourth layers
      of the rectal wall. EUS-FNA was performed, and the content of the cystic lesion
      was transparent mucinous liquid. Histologically, the specimen revealed PAS and
      Alcian blue-positive mucinous material and a small number of inflammatory cells
      such as foamy macrophages. Therefore, this cystic lesion was diagnosed as a
      rectal implantation cyst.

PMID- 22139492
TI  - [A case of non-alcoholic fatty liver disease (NAFLD) aggravated after treatment
      with raloxifene].
AB  - A 70-year-old woman presented with abnormal liver function test 3 months after
      the introduction of daily intake of raloxifene, a selective estrogen receptor
      modulator, for osteoporosis. She had a history of NAFLD, diabetes mellitus and
      depression. The ratio of the computed-tomographic value of the liver against that
      of the spleen decreased remarkably. Pathological examination of the liver biopsy
      revealed severe steatosis. We thought her NAFLD was aggravated by raloxifene and
      discontinued the drug. The liver function test results improved and the computed
      tomographic liver-spleen ratio rose. This is the second case report of NAFLD
      becoming aggravated after treatment with raloxifene. It still remains unclear how
      raloxifene affects liver. Monitoring liver function is recommended when treating
      with raloxifene.

PMID- 22139493
TI  - [Signet ring cell carcinoma of the bile duct: a case report].
AB  - A 72-year-old man was admitted with obstructive jaundice. Computed tomography
      revealed a 4cm tumor with multiple cystic components obstructing the common bile
      duct. Endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography
      and intraductal ultrasonography demonstrated the tumor, which derived from the
      lower bile duct, grew into the bile duct lumen. Peroral cholangioscopy revealed
      distended tumor vessels on the surface of the tumor. Signet ring cell carcinoma
      of the bile duct was diagnosed by biopsy. The patient died 3 months after the
      first hospital admission despite chemotherapy.

PMID- 22139494
TI  - [An autopsy case of retroperitoneal paraganglioma that had presented with
      pheochromocytoma multisystem crisis].
AB  - A 40's woman was seen at the emergency room because of severe back pain and
      vomiting. Abdominal CT scan revealed a tumor about 7cm in diameter located on the
      retroperitoneum. For 6 hours after admission, her body temperature was 39 degrees
      C and respiratory failure occurred. After 30 hours, the patient died because of a
      complication in circulatory failure. From the abnormally high level of
      catecholamines in the blood and autopsy results, we determined that
      pheochromocytoma multisystem crisis had been caused by the retroperitoneal
      paraganglioma.

PMID- 22139495
TI  - Disorders of the degradation of branched chain amino acids: what is new in
      clinics and laboratories?

PMID- 22139496
TI  - Decreased serum antioxidant capacity in patients with Wilson disease is
      associated with neurological symptoms.
AB  - BACKGROUND & AIMS: Wilson disease (WD) is an inherited disorder of copper
      disposition caused by an ATP7B transporter gene mutation, leading to copper
      accumulation in predisposed tissues. In addition to a genetic predisposition,
      other factors are likely to contribute to its clinical manifestation. The aim of
      the study was to assess whether oxidative stress affects the phenotypic
      manifestation of WD. METHODS: In 56 patients with WD (29 men; 26 with the hepatic
      form, 22 with the neurologic form, and eight asymptomatic; mean age 38.5 +/- 12
      years), total serum antioxidant capacity (TAC) and inflammatory parameters (hs
      CRP, IL-1beta, IL-2, IL-6, IL-10, and TNF-alpha) were analyzed and related to the
      clinical manifestation, and mutations of the ATP7B gene. The control group for
      the TAC and inflammatory parameters consisted of 50 age- and gender-matched
      healthy individuals. RESULTS: WD patients had a significantly lower TAC (p <
      0.00001), lower IL-10 levels (p = 0.039), as well as both higher IL-1beta (p =
      0.019) and IL-6 (p = 0.005) levels compared to the control subjects. TNF-alpha,
      hs-CRP, and IL-2 did not differ from the controls. Patients with the neurological
      form of WD had a significantly lower TAC than those with the hepatic form (p <
      0.001). In addition, the lower TAC was associated with the severity of the
      neurological symptoms (p = 0.02). No relationship between the inflammatory
      parameters and clinical symptoms was found. CONCLUSIONS: Data from our study
      suggest that the increased oxidative stress contributes significantly to the
      clinical manifestation of WD; as a lower TAC is associated with the neurological
      symptoms in WD patients.

PMID- 22139497
TI  - Severe intestinal oedema due to nephrotic syndrome.

PMID- 22139498
TI  - Serum 'free' copper in Wilson disease.
AB  - BACKGROUND: The relationship between serum 'free' copper and urine copper in
      patients with Wilson disease has not been explored. AIM: The object of this study
      is to ascertain if there is a direct relationship between these two parameters.
      METHOD: The case notes of 320 patients with Wilson disease, seen between 1960 and
      1987, have been reviewed. Eighty of these patients had received no treatment
      before referral and the results of serum 'free' copper and urine copper on
      admission and at one year of treatment have been analysed. RESULTS: Except for
      patients with acute haemolysis, the ratio between 'free' serum copper and urine
      copper before treatment, on average, is around 7:1, after treatment this falls to
      around 5:1. But results show a wide scatter and there is no direct linear
      relationship. CONCLUSION: The term 'free' copper is misleading and should be
      replaced by the more cumbersome but accurate term 'noncaeruloplasmin bound
      copper'. Most 'free' copper is complexed to albumin and is only available for
      excretion if there is significant protein loss by the kidneys.

PMID- 22139499
TI  - Unexpected restriction.

PMID- 22139500
TI  - Cellular orchestrators of renal fibrosis.
AB  - Renal fibrosis is a key determinant of the progression of many renal diseases and
      represents a final common pathway that adversely affects outcome. The evolution
      of renal fibrosis is complicated and involves many cellular and molecular
      mediators. In this review we will outline the key players in the fibrotic
      response of the injured kidney and discuss emerging research in the field.

PMID- 22139501
TI  - Primary jejunal mucosa-associated lymphoid tissue lymphoma.

PMID- 22139502
TI  - A transposon site hybridization screen identifies galU and wecBC as important for
      survival of Yersinia pestis in murine macrophages.
AB  - Yersinia pestis is able to survive and replicate within murine macrophages.
      However, the mechanism by which Y. pestis promotes its intracellular survival is
      not well understood. To identify genes that are important for Y. pestis survival
      in macrophages, a library comprised of ~31,500 Y. pestis KIM6+ transposon
      insertion mutants (input pool) was subjected to negative selection in primary
      murine macrophages. Genes underrepresented in the output pool of surviving
      bacteria were identified by transposon site hybridization to DNA oligonucleotide
      microarrays. The screen identified several genes known to be important for
      survival of Y. pestis in macrophages, including phoPQ and members of the PhoPQ
      regulon (e.g., pmrF). In addition, genes predicated to encode a glucose-1
      phosphate uridylyltransferase (galU), a UDP-N-acetylglucosamine 2-epimerase
      (wecB) and a UDP-N-acetyl-d-mannosamine dehydrogenase (wecC) were identified in
      the screen. Viable-count assays demonstrated that a KIM6+ galU mutant and a KIM6+
      wecBC mutant were defective for survival in murine macrophages. The galU mutant
      was studied further because of its strong phenotype. The KIM6+ galU mutant
      exhibited increased susceptibility to the antimicrobial peptides polymyxin B and
      cathelicidin-related antimicrobial peptide (CRAMP). Polyacrylamide gel
      electrophoresis demonstrated that the lipooligosaccharide (LOS) of the galU
      mutant migrated faster than the LOS of the parent KIM6+, suggesting the core was
      truncated. In addition, the analysis of LOS isolated from the galU mutant by mass
      spectrometry showed that aminoarabinose modification of lipid A is absent.
      Therefore, addition of aminoarabinose to lipid A and complete LOS core (galU), as
      well as enterobacterial common antigen (wecB and wecC), is important for survival
      of Y. pestis in macrophages.

PMID- 22139503
TI  - The sulfur oxygenase reductase from the mesophilic bacterium Halothiobacillus
      neapolitanus is a highly active thermozyme.
AB  - A biochemical, biophysical, and phylogenetic study of the sulfur oxygenase
      reductase (SOR) from the mesophilic gammaproteobacterium Halothiobacillus
      neapolitanus (HnSOR) was performed in order to determine the structural and
      biochemical properties of the enzyme. SOR proteins from 14 predominantly
      chemolithoautotrophic bacterial and archaeal species are currently available in
      public databases. Sequence alignment and phylogenetic analysis showed that they
      form a coherent protein family. The HnSOR purified from Escherichia coli after
      heterologous gene expression had a temperature range of activity of 10 to 99
      degrees C with an optimum at 80 degrees C (42 U/mg protein). Sulfite,
      thiosulfate, and hydrogen sulfide were formed at various stoichiometries in a
      range between pH 5.4 and 11 (optimum pH 8.4). Circular dichroism (CD)
      spectroscopy and dynamic light scattering showed that the HnSOR adopts secondary
      and quaternary structures similar to those of the 24-subunit enzyme from the
      hyperthermophile Acidianus ambivalens (AaSOR). The melting point of the HnSOR was
      ~20 degrees C lower than that of the AaSOR, when analyzed with CD-monitored
      thermal unfolding. Homology modeling showed that the secondary structure elements
      of single subunits are conserved. Subtle changes in the pores of the outer shell
      and increased flexibility might contribute to activity at low temperature. We
      concluded that the thermostability was the result of a rigid protein core
      together with the stabilizing effect of the 24-subunit hollow sphere.

PMID- 22139504
TI  - Role of the Umo proteins and the Rcs phosphorelay in the swarming motility of the
      wild type and an O-antigen (waaL) mutant of Proteus mirabilis.
AB  - Proteus mirabilis is a Gram-negative bacterium that exists as a short rod when
      grown in liquid medium, but during growth on surfaces it undergoes a distinct
      physical and biochemical change that culminates in the formation of a swarmer
      cell. How P. mirabilis senses a surface is not fully understood; however, the
      inhibition of flagellar rotation and accumulation of putrescine have been
      proposed to be sensory mechanisms. Our lab recently isolated a transposon
      insertion in waaL, encoding O-antigen ligase, that resulted in a loss of swarming
      but not swimming motility. The waaL mutant failed to activate flhDC, the class 1
      activator of the flagellar gene cascade, when grown on solid surfaces. Swarming
      in the waaL mutant was restored by overexpression of flhDC in trans or by a
      mutation in the response regulator rcsB. To further investigate the role of the
      Rcs signal transduction pathway and its possible relationship with O-antigen
      surface sensing, mutations were made in the rcsC, rcsB, rcsF, umoB (igaA), and
      umoD genes in wild-type and waaL backgrounds. Comparison of the swarming
      phenotypes of the single and double mutants and of strains overexpressing
      combinations of the UmoB, UmoD, and RcsF proteins demonstrated the following: (i)
      there is a differential effect of RcsF and UmoB on swarming in wild-type and waaL
      backgrounds, (ii) RcsF inhibits UmoB activity but not UmoD activity in a wild
      type background, and (iii) UmoD is able to modulate activity of the Rcs system.

PMID- 22139505
TI  - Lag phase is a distinct growth phase that prepares bacteria for exponential
      growth and involves transient metal accumulation.
AB  - Lag phase represents the earliest and most poorly understood stage of the
      bacterial growth cycle. We developed a reproducible experimental system and
      conducted functional genomic and physiological analyses of a 2-h lag phase in
      Salmonella enterica serovar Typhimurium. Adaptation began within 4 min of
      inoculation into fresh LB medium with the transient expression of genes involved
      in phosphate uptake. The main lag-phase transcriptional program initiated at 20
      min with the upregulation of 945 genes encoding processes such as transcription,
      translation, iron-sulfur protein assembly, nucleotide metabolism, LPS
      biosynthesis, and aerobic respiration. ChIP-chip revealed that RNA polymerase was
      not "poised" upstream of the bacterial genes that are rapidly induced at the
      beginning of lag phase, suggesting a mechanism that involves de novo partitioning
      of RNA polymerase to transcribe 522 bacterial genes within 4 min of leaving
      stationary phase. We used inductively coupled plasma mass spectrometry (ICP-MS)
      to discover that iron, calcium, and manganese are accumulated by S. Typhimurium
      during lag phase, while levels of cobalt, nickel, and sodium showed distinct
      growth-phase-specific patterns. The high concentration of iron during lag phase
      was associated with transient sensitivity to oxidative stress. The study of lag
      phase promises to identify the physiological and regulatory processes responsible
      for adaptation to new environments.

PMID- 22139507
TI  - Synthetic lethality of the lytE cwlO genotype in Bacillus subtilis is caused by
      lack of D,L-endopeptidase activity at the lateral cell wall.
AB  - Bacterial peptidoglycan acts as an exoskeleton to protect the bacterial cell.
      Although peptidoglycan biosynthesis by penicillin-binding proteins is well
      studied, few studies have described peptidoglycan disassembly, which is necessary
      for a dynamic structure that allows cell growth. In Bacillus subtilis, more than
      35 genes encoding cell wall lytic enzymes have been identified; however, only two
      D,L-endopeptidases (lytE and cwlO) are involved in cell proliferation. In this
      study, we demonstrated that the D,L-endopeptidase activity at the lateral cell
      wall is essential for cell proliferation. Inactivation of LytE and CwlO by point
      mutation of the catalytic residues caused cell growth defects. However, the
      forced expression of LytF or CwlS, which are paralogs of LytE, did not suppress
      lytE cwlO synthetic lethality. Subcellular localization studies of these D,L
      endopeptidases showed LytF and CwlS at the septa and poles, CwlO at the
      cylindrical part of the cell, and LytE at the septa and poles as well as the
      cylindrical part. Furthermore, construction of N-terminal and C-terminal domain
      swapped enzymes of LytE, LytF, CwlS, and CwlO revealed that localization was
      dependent on the N-terminal domains. Only the chimeric proteins that were
      enzymatically active and localized to the sidewall were able to suppress the
      synthetic lethality, suggesting that the lack of D,L-endopeptidase activity at
      the cylindrical part of the cell leads to a growth defect. The functions of LytE
      and CwlO in cell morphogenesis were discussed.

PMID- 22139506
TI  - Genome-scale metabolic reconstruction and hypothesis testing in the methanogenic
      archaeon Methanosarcina acetivorans C2A.
AB  - Methanosarcina acetivorans strain C2A is a marine methanogenic archaeon notable
      for its substrate utilization, genetic tractability, and novel energy
      conservation mechanisms. To help probe the phenotypic implications of this
      organism's unique metabolism, we have constructed and manually curated a genome
      scale metabolic model of M. acetivorans, iMB745, which accounts for 745 of the
      4,540 predicted protein-coding genes (16%) in the M. acetivorans genome. The
      reconstruction effort has identified key knowledge gaps and differences in
      peripheral and central metabolism between methanogenic species. Using flux
      balance analysis, the model quantitatively predicts wild-type phenotypes and is
      96% accurate in knockout lethality predictions compared to currently available
      experimental data. The model was used to probe the mechanisms and energetics of
      by-product formation and growth on carbon monoxide, as well as the nature of the
      reaction catalyzed by the soluble heterodisulfide reductase HdrABC in M.
      acetivorans. The genome-scale model provides quantitative and qualitative
      hypotheses that can be used to help iteratively guide additional experiments to
      further the state of knowledge about methanogenesis.

PMID- 22139508
TI  - Role of ArlRS in autolysis in methicillin-sensitive and methicillin-resistant
      Staphylococcus aureus strains.
AB  - Autolysis plays an essential role in bacterial cell division and lysis with beta
      lactam antibiotics. Accordingly, the expression of autolysins is tightly
      regulated by several endogenous regulators, including ArlRS, a two component
      regulatory system that has been shown to negatively regulate autolysis in
      methicillin-sensitive Staphylococcus aureus (MSSA) strains. In this study, we
      found that inactivation of arlRS does not play a role in autolysis of methicillin
      resistant S. aureus (MRSA) strains, such as community-acquired (CA)-MRSA strains
      USA300 and MW2 or the hospital-acquired (HA)-MRSA strain COL. This contrasts with
      MSSA strains, including Newman, SH1000, RN6390, and 8325-4, where autolysis is
      affected by ArlRS. We further demonstrated that the striking difference in the
      roles of arlRS between MSSA and MRSA strains is not due to the methicillin
      resistance determinant mecA. Among known autolysins and their regulators, we
      found that arlRS represses lytN, while no effect was seen on atl, lytM, and lytH
      expression in both CA- and HA-MRSA strains. Transcriptional-fusion assays showed
      that the agr transcripts, RNAII and RNAIII, were significantly more downregulated
      in the arlRS mutant of MW2 than the MSSA strain Newman. Importantly, provision of
      agr RNAIII in trans to the MW2 arlRS mutant via a multicopy plasmid induced
      autolysis in this MRSA strain. Also, the autolytic phenotype in the arlRS mutant
      of MSSA strain Newman could be rescued by a mutation in either atl or lytM.
      Together, these data showed that ArlRS impacts autolysis differently in MSSA and
      MRSA strains.

PMID- 22139510
TI  - May cyclic nucleotides be a source for abiotic RNA synthesis?
AB  - Nucleic bases are obtained by heating formamide in the presence of various
      catalysts. Formamide chemistry also allows the formation of acyclonucleosides and
      the phosphorylation of nucleosides in every possible position, also affording
      2',3' and 3',5' cyclic forms. We have reported that 3',5' cyclic GMP and 3',5'
      cyclic AMP polymerize in abiotic conditions yielding short oligonucleotides. The
      characterization of this reaction is being pursued, several of its parameters
      have been determined and experimental caveats are reported. The yield of non
      enzymatic polymerization of cyclic purine nucleotides is very low. Polymerization
      is strongly enhanced by the presence of base-complementary RNA sequences.

PMID- 22139509
TI  - Proline utilization by Bacillus subtilis: uptake and catabolism.
AB  - L-Proline can be used by Bacillus subtilis as a sole source of carbon or
      nitrogen. We traced L-proline utilization genetically to the putBCP (ycgMNO)
      locus. The putBCP gene cluster encodes a high-affinity proline transporter (PutP)
      and two enzymes, the proline dehydrogenase PutB and the Delta(1)-pyrroline-5
      carboxylate dehydrogenase PutC, which jointly catabolize L-proline to L
      glutamate. Northern blotting, primer extension, and putB-treA reporter gene
      fusion analysis showed that the putBCP locus is transcribed as an L-proline
      inducible operon. Its expression was mediated by a SigA-type promoter and was
      dependent on the proline-responsive PutR activator protein. Induction of putBCP
      expression was triggered by the presence of submillimolar concentrations of L
      proline in the growth medium. However, the very large quantities of L-proline (up
      to several hundred millimolar) synthesized by B. subtilis as a stress protectant
      against high osmolarity did not induce putBCP transcription. Induction of putBCP
      transcription by external L-proline was not dependent on L-proline uptake via the
      substrate-inducible PutP or the osmotically inducible OpuE transporter. It was
      also not dependent on the chemoreceptor protein McpC required for chemotaxis
      toward L-proline. Our findings imply that B. subtilis can distinguish externally
      supplied L-proline from internal L-proline pools generated through de novo
      synthesis. The molecular basis of this regulatory phenomenon is not understood.
      However, it provides the B. subtilis cell with a means to avoid a futile cycle of
      de novo L-proline synthesis and consumption by not triggering the expression of
      the putBCP L-proline catabolic genes in response to the osmoadaptive production
      of the compatible solute L-proline.

PMID- 22139511
TI  - Primordial ocean chemistry and its compatibility with the RNA world.
AB  - We examine the stability of three key components needed to establish an RNA World
      under a range of potential conditions present on the early earth. The stability
      of ribose, cytosine, and the phosphodiester bond are estimated at different pH
      values and temperatures by extrapolating available experimental data. The
      conditions we have chosen range from highly acidic or alkaline hydrothermal
      vents, to the milder conditions in a primordial ocean at a range of atmospheric
      CO(2) partial pressures.

PMID- 22139512
TI  - Modeling free energy availability from Hadean hydrothermal systems to the first
      metabolism.
AB  - Off-axis Hydrothermal Systems (HSs) are seen as the possible setting for the
      emergence of life. As the availability of free energy is a general requirement to
      drive any form of metabolism, we ask here under which conditions free energy
      generation by geologic processes is greatest and relate these to the conditions
      found at off-axis HSs. To do so, we present a conceptual model in which we
      explicitly capture the energetics of fluid motion and its interaction with
      exothermic reactions to maintain a state of chemical disequilibrium. Central to
      the interaction is the temperature at which the exothermic reactions take place.
      This temperature not only sets the equilibrium constant of the chemical reactions
      and thereby the distance of the actual state to chemical equilibrium, but these
      reactions also shape the temperature gradient that drives convection and thereby
      the advection of reactants to the reaction sites and the removal of the products
      that relate to geochemical free energy generation. What this conceptual model
      shows is that the positive feedback between convection and the chemical kinetics
      that is found at HSs favors a greater rate of free energy generation than in the
      absence of convection. Because of the lower temperatures and because the
      temperature of reactions is determined more strongly by these dynamics rather
      than an external heat flux, the conditions found at off-axis HSs should result in
      the greatest rates of geochemical free energy generation. Hence, we hypothesize
      from these thermodynamic considerations that off-axis HSs seem most conducive for
      the emergence of protometabolic pathways as these provide the greatest, abiotic
      generation rates of chemical free energy.

PMID- 22139513
TI  - Habitability of extrasolar planets and tidal spin evolution.
AB  - Stellar radiation has conservatively been used as the key constraint to planetary
      habitability. We review here the effects of tides, exerted by the host star on
      the planet, on the evolution of the planetary spin. Tides initially drive the
      rotation period and the orientation of the rotation axis into an equilibrium
      state but do not necessarily lead to synchronous rotation. As tides also
      circularize the orbit, eventually the rotation period does equal the orbital
      period and one hemisphere will be permanently irradiated by the star.
      Furthermore, the rotational axis will become perpendicular to the orbit, i.e. the
      planetary surface will not experience seasonal variations of the insolation. We
      illustrate here how tides alter the spins of planets in the traditional habitable
      zone. As an example, we show that, neglecting perturbations due to other
      companions, the Super-Earth Gl581d performs two rotations per orbit and that any
      primordial obliquity has been eroded.

PMID- 22139514
TI  - Enhanced synthesis of alkyl amino acids in Miller's 1958 H2S experiment.
AB  - Stanley Miller's 1958 H(2)S-containing experiment, which included a simulated
      prebiotic atmosphere of methane (CH(4)), ammonia (NH(3)), carbon dioxide (CO(2)),
      and hydrogen sulfide (H(2)S) produced several alkyl amino acids, including the
      alpha-, beta-, and gamma-isomers of aminobutyric acid (ABA) in greater relative
      yields than had previously been reported from his spark discharge experiments. In
      the presence of H(2)S, aspartic and glutamic acids could yield alkyl amino acids
      via the formation of thioimide intermediates. Radical chemistry initiated by
      passing H(2)S through a spark discharge could have also enhanced alkyl amino acid
      synthesis by generating alkyl radicals that can help form the aldehyde and ketone
      precursors to these amino acids. We propose mechanisms that may have influenced
      the synthesis of certain amino acids in localized environments rich in H(2)S and
      lightning discharges, similar to conditions near volcanic systems on the early
      Earth, thus contributing to the prebiotic chemical inventory of the primordial
      Earth.

PMID- 22139515
TI  - Delivery of complex organic compounds from evolved stars to the solar system.
AB  - Stars in the late stages of evolution are able to synthesize complex organic
      compounds with aromatic and aliphatic structures over very short time scales.
      These compounds are ejected into the interstellar medium and distributed
      throughout the Galaxy. The structures of these compounds are similar to the
      insoluble organic matter found in meteorites. In this paper, we discuss to what
      extent stellar organics has enriched the primordial Solar System and possibly the
      early Earth.

PMID- 22139516
TI  - Progress in studies on the RNA world.
AB  - The montmorillonite-catalyzed reactions of D, L-ImpA with D, L-ImpU generates RNA
      like oligomers. The structures of the dimers to pentamers were investigated and
      homochiral products were identified in greater amounts than would be expected if
      theoretical amounts of each were formed. The homochirality increased from 64% to
      97% as the chain length increased from dimers to pentamers. Investigation of the
      effect of pH, occupancy of the interlayer space and the influence of various
      cations in the reaction provided further insight into physical process in the
      mechanism of the catalysis. A detailed analysis of dimers was carried out in view
      of there being key intermediates towards formation of higher oligomers. The study
      was extended to the synthesis of non-standard dimers including those formed with
      deoxy-ribonucleotides.

PMID- 22139517
TI  - Multiple paths to encephalization and technical civilizations.
AB  - We propose consideration of at least two possible evolutionary paths for the
      emergence of intelligent life with the potential for technical civilization. The
      first is the path via encephalization of homeothermic animals; the second is the
      path to swarm intelligence of so-called superorganisms, in particular the social
      insects. The path to each appears to be facilitated by environmental change:
      homeothermic animals by decreased climatic temperature and for swarm intelligence
      by increased oxygen levels.

PMID- 22139518
TI  - Self-assembly and self-replication of short amphiphilic beta-sheet peptides.
AB  - Most self-replicating peptide systems are made of alpha-helix forming sequences.
      However, it has been postulated that shorter and simpler peptides may also serve
      as templates for replication when arranged into well-defined structures. We
      describe here the design and characterization of new peptides that form soluble
      beta-sheet aggregates that serve to significantly accelerate their ligation and
      self-replication. We then discuss the relevance of these phenomena to early
      molecular evolution, in light of additional functionality associated with beta
      sheet assemblies.

PMID- 22139519
TI  - Detection of peptidic sequences in the ancient acidic sediments of Rio Tinto,
      Spain.
AB  - Biomarkers are molecules that are produced by or can be associated with
      biological activities. They can be used as tracers that give us an idea of the
      ancient biological communities that produced them, the paleoenvironmental
      conditions where they lived, or the mechanism involved in their transformation
      and preservation. As a consequence, the preservation potential of molecules over
      time depends largely on their nature, but also on the conditions of the
      environment, which controls the decomposition kinetics. In this context, proteins
      and nucleic acids, which are biomolecules bearing biological information, are
      among the most labile molecules. In this research, we report the presence of
      short-chained peptides obtained from extracts of ferruginous sedimentary deposits
      that have been produced under the acidic and oxidizing solutions of Rio Tinto,
      Spain. These preliminary results go against the paradigmatic idea that considers
      the acidic and oxidizing environments inappropriate for the preservation of
      molecular information.

PMID- 22139520
TI  - Development of a model to compute the extension of life supporting zones for
      Earth-like exoplanets.
AB  - A radiative convective model to calculate the width and the location of the life
      supporting zone (LSZ) for different, alternative solvents (i.e. other than water)
      is presented. This model can be applied to the atmospheres of the terrestrial
      planets in the solar system as well as (hypothetical, Earth-like) terrestrial
      exoplanets. Cloud droplet formation and growth are investigated using a cloud
      parcel model. Clouds can be incorporated into the radiative transfer
      calculations. Test runs for Earth, Mars and Titan show a good agreement of model
      results with observations.

PMID- 22139521
TI  - A mathematical model for evolution and SETI.
AB  - Darwinian evolution theory may be regarded as a part of SETI theory in that the
      factor f(l) in the Drake equation represents the fraction of planets suitable for
      life on which life actually arose. In this paper we firstly provide a statistical
      generalization of the Drake equation where the factor f(l) is shown to follow the
      lognormal probability distribution. This lognormal distribution is a consequence
      of the Central Limit Theorem (CLT) of Statistics, stating that the product of a
      number of independent random variables whose probability densities are unknown
      and independent of each other approached the lognormal distribution when the
      number of factors increased to infinity. In addition we show that the exponential
      growth of the number of species typical of Darwinian Evolution may be regarded as
      the geometric locus of the peaks of a one-parameter family of lognormal
      distributions (b-lognormals) constrained between the time axis and the
      exponential growth curve. Finally, since each b-lognormal distribution in the
      family may in turn be regarded as the product of a large number (actually "an
      infinity") of independent lognormal probability distributions, the mathematical
      way is paved to further cast Darwinian Evolution into a mathematical theory in
      agreement with both its typical exponential growth in the number of living
      species and the Statistical Drake Equation.

PMID- 22139522
TI  - Novel inhibitors to Taenia solium Cu/Zn superoxide dismutase identified by
      virtual screening.
AB  - We describe in this work a successful virtual screening and experimental testing
      aimed to the identification of novel inhibitors of superoxide dismutase of the
      worm Taenia solium (TsCu/Zn-SOD), a human parasite. Conformers from
      LeadQuest((r)) database of drug-like compounds were selected and then docked on
      the surface of TsCu/Zn-SOD. Results were screened looking for ligand contacts
      with receptor side-chains not conserved in the human homologue, with a subsequent
      development of a score optimization by a set of energy minimization steps, aimed
      to identify lead compounds for in vitro experiments. Six out of fifty
      experimentally tested compounds showed MUM inhibitory activity toward TsCu/Zn
      SOD. Two of them showed species selectivity since did not inhibit the homologous
      human enzyme when assayed in vitro.

PMID- 22139523
TI  - Effects of media reports and the subsequent voluntary withdrawal from sale of
      suicide-related products on the suicide rate in Japan.
AB  - Media reports of suicides have an impact on suicide rates. However,
      countermeasures to this media effect have not been evaluated. We examined the
      association between media reports of suicides accomplished with the use of
      hydrogen sulfide, the voluntary stoppage of sales of suicide-related products,
      and suicide rates for people in their 20s, 30s, and 40s in Japan. The Box-Jenkins
      transfer function model was applied to monthly time series data from February
      2003 to December 2009 (83 months). In the male suicide time series, media reports
      of suicide were not related to suicide counts (omega((R)) = 8.988, P = 0.694).
      Similarly, stopping the sale of bath salts was not related to the number of
      suicides (omega((S)) = -7.344, P = 0.694). However, in the female suicide time
      series, media reports of suicide were related to the number of suicides
      (omega((R)) = 17.225, P = 0.049). Similarly, stopping the sale of bath salts was
      related to the number of suicides (omega((S)) = -18.545, P = 0.040). The results
      suggest that stopping the sale of bath salts might be effective in reducing the
      number of copycat suicides among the women in their 20s, 30s, and 40s. In
      practice, stopping the sale of suicide-related products might be a potentially
      effective countermeasure to prevent copycat suicides triggered by media coverage
      of suicides.

PMID- 22139524
TI  - Determination of synthetic polycyclic musks in aqueous samples by ultrasound
      assisted dispersive liquid-liquid microextraction and gas chromatography-mass
      spectrometry.
AB  - A simple and solvent-minimized procedure for the determination of six commonly
      found synthetic polycyclic musks in aqueous samples using ultrasound-assisted
      dispersive liquid-liquid microextraction (UA-DLLME) coupled with gas
      chromatography-mass spectrometry (GC-MS) is described. The parameters affecting
      the extraction efficiency of analytes from water samples were systematically
      investigated. The best extraction conditions involved the rapid injection of a
      mixture of 1.0 mL of isopropyl alcohol (as a dispersant) and 10 MUL of carbon
      tetrachloride (as an extractant) into 10 mL of water containing 0.5 g of sodium
      chloride in a conical-bottom glass tube. After ultrasonication for 1.0 min and
      centrifugation at 5,000 rpm (10 min), the sedimented phase 1.0 MUL was directly
      injected into the GC-MS system. The limits of quantitation (LOQs) were less than
      0.6 ng/L. The precision for these analytes, as indicated by relative standard
      deviations (RSDs), was less than 11% for both intra- and interday analysis.
      Accuracy, expressed as the mean extraction recovery, was between 71 and 104%.
      Their total concentrations were determined in the range from 8.3 to 63.9 ng/L in
      various environmental samples by using a standard addition method.

PMID- 22139525
TI  - Computational analysis of non-covalent polymer-protein interactions governing
      antibody orientation.
AB  - The ALYGNSA is an affinity-based antibody orientation system produced through the
      interaction of the polymer poly(methyl methacrylate) (PMMA) and recombinant
      protein G (rProG), a streptococcal protein. This improved orientation suggests a
      specific non-covalent attachment of the rProG to PMMA that leaves the IgG binding
      region of the rProG more readily available. In this study, a full tertiary
      structure model of the rProG molecule of 198 amino acid residues containing a
      signal region, two IgG binding domains, and an anchor region, was computationally
      generated using the iterative threading assembly refinement (I-Tasser) server.
      The rProG model having the highest confidence score was subject to docking
      experiments with varied-length short chains of PMMA polymer via the graphic
      processing units-based Hex server. A five-residue section of the rProG anchor
      region, with the sequence TPATP, was identified as a potential interaction site.
      A complete ternary model (rProG, PMMA, and IgG) was assembled and provides
      insight into a plausible mechanism for non-covalent antibody orientation by the
      ALYGNSA system.

PMID- 22139526
TI  - Accumulation of argpyrimidine, a methylglyoxal-derived advanced glycation end
      product, increases apoptosis of lens epithelial cells both in vitro and in vivo.
AB  - The formation of advanced glycation end products (AGEs) has been considered to be
      a potential causative factor of injury to lens epithelial cells (LECs). Damage of
      LECs is believed to contribute to cataract formation. The purpose of this study
      was to investigate the cytotoxic effect of AGEs on LECs both in vitro and in
      vivo. We examined the accumulation of argpyrimidine, a methylglyoxal-derived AGE,
      and the expression of apoptosis-related molecules including nuclear factor-
      kappaB (NF-kappaB), Bax, and Bcl-2 in the human LEC line HLE-B3 and in
      cataractous lenses of Zucker diabetic fatty (ZDF) rats, an animal model of type 2
      diabetes. In cataractous lenses from twenty-oneweek- old ZDF rats, LEC apoptosis
      was markedly increased, and the accumulation of argpyrimidine as well as
      subsequent activation of NF-kappaB in LECs were significantly enhanced. The ratio
      of Bax to Bcl-2 protein levels was also increased. In addition, the accumulation
      of argpyrimidine triggered apoptosis in methylglyoxal- treated HLE-B3 cells.
      However, the presence of pyridoxamine (an AGEs inhibitor) and pyrrolidine
      dithiocarbamate (a NF-kappaB inhibitor) prevented apoptosis in HLE-B3 cells
      through the inhibition of argpyrimidine formation and the blockage of NF-kappaB
      nuclear translocalization, respectively. These results suggest that the cellular
      accumulation of argpyrimidine in LECs is NF-kappaB-dependent and pro-apoptotic.

PMID- 22139527
TI  - Myocardial edema imaging by cardiovascular magnetic resonance: current status and
      future potential.
AB  - Cardiovascular magnetic resonance (CMR) imaging is widely established, free of
      radioactive material or ionizing radiation, and the accepted noninvasive gold
      standard for numerous noninvasive cardiac markers. Using a technique called T2
      weighted imaging, CMR can be used to assess myocardial edema as a reliable marker
      for acute, potentially reversible myocardial injury. Contrast agents are not
      required as the myocardial free water content affects the magnetic properties of
      the tissue, thus providing inherent image contrast. In this review, we illustrate
      the utility of T2-weighted techniques in the assessment of myocardial edema in a
      range of clinical scenarios. The detection of myocardial edema is clinically
      relevant in many acute settings and may be further helpful to better understand
      the pathophysiology of many non-acute clinical diseases. Currently, T2-weighted
      CMR represents the only imaging modality that can accurately depict and quantify
      the presence of myocardial edema in a noninvasive fashion. Thus, T2-weighted
      imaging should be included in a comprehensive CMR imaging protocol, especially if
      an acute injury is suspected.

PMID- 22139528
TI  - Tight blood pressure control in diabetes: evidence-based review of treatment
      targets in patients with diabetes.
AB  - Blood pressure (BP) targets in diabetic patients stills represent the object of a
      major debate, fueled by the recent publication of post hoc observational analyses
      of the INVEST and the ONTARGET trials, suggesting an increased risk of
      cardiovascular events with tighter control, the J-curve effect, and by the
      results of the ACCORD trial, showing no improvements in the composite primary
      outcome of nonfatal myocardial infarction, stroke, or cardiovascular death in the
      intensive BP-lowering arm (<120/80 mmHg). In the present review, we focus on
      existing evidence about different BP targets in diabetic subjects and we present
      the results of our recent meta-analysis, showing that tight BP control may
      significantly reduce the risk of stroke in these patients without increasing the
      risk of myocardial infarction. Therapeutic inertia (leaving diabetic patients
      with BP values of 140/90 mmHg or higher) should be avoided at all costs, as this
      would lead to an unacceptable toll in terms of human lives, suffering, and
      socioeconomic costs.

PMID- 22139529
TI  - Segmental odontomaxillary dysplasia: report of 3 cases and literature review.
AB  - Segmental Odontomaxillary Dysplasia (SOD) is an uncommon developmental disorder
      of unknown etiology that causes a unilateral alteration of the maxilla associated
      with an abnormal growth and maturation of bone, lack of one or both premolars and
      delayed tooth eruption on the affected side, alteration of adjacent gingival
      tissue with or without facial cutaneous lesions. Radiographically is observed an
      irregular trabecular pattern and reduction of the maxillary sinus. There are 50
      cases reported in the English-language literature. A literature review is herein
      presented emphasizing the clinical, radiographic, and histological features, and
      three additional cases of SOD affecting a 22 years-old woman, a 18 years-old man,
      and a 5 years-old boy, respectively are described.

PMID- 22139531
TI  - Simultaneous saccharification and fermentation (SSF) of Jatropha curcas shells:
      utilization of co-products from the biodiesel production process.
AB  - Jatropha curcas has great potential as an oil crop for use in biodiesel
      applications, and the outer shell is rich in lignocellulose that may be converted
      to ethanol, giving rise to the concept of a biorefinery. In this study, two
      dilute pretreatments of 0.5% H(2)SO(4) and 1.0% NaOH were performed on Jatropha
      shells with subsequent simultaneous saccharification and fermentation (SSF) of
      the pretreated water-insoluble solids (WIS) to evaluate the effect of inhibitors
      in the pretreatment slurry. A cellulase loading of 15 FPU/g WIS, complimented
      with an excess of cellobiase (19.25 U/g), was used for SSF of either the washed
      WIS or the original slurry to determine the effect of inhibitors. Ethanol and
      glucose were monitored during SSF of 20 g of pretreated biomass. The unwashed
      slurry showed to have a positive effect on SSF efficiency for the NaOH-pretreated
      biomass. Maximum efficiencies of glucan conversion to ethanol in the WIS were
      40.43% and 41.03% for the H(2)SO(4)- and NaOH-pretreated biomasses, respectively.

PMID- 22139530
TI  - A huge intraventricular congenital anaplastic astrocytoma: case report with
      histopathological and genetic consideration.
AB  - Congenital malignant gliomas are rare brain tumors about which few reports have
      been published. We present the clinical course and genetic alterations in an
      infant with a congenital malignant glioma detected incidentally by
      ultrasonography at 36 weeks. The tumor occupied the right temporoparietal region,
      extended to the posterior fossa, and significantly compressed surrounding
      structures. The female infant was entirely normal without macrocrania, tense
      fontanel, or sucking difficulties. The tumor was subtotally resected by two-stage
      surgery; pathological diagnosis was anaplastic astrocytoma. Immunohistochemical
      staining was positive for p53 and negative for epidermal growth factor receptor.
      There was no O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter
      methylation, no 1p/19q loss of heterozygosity, and no isocitrate dehydrogenase 1
      (IDH1) mutation. She underwent postoperative chemotherapy and is alive and well
      12 months after surgery.

PMID- 22139532
TI  - Predicting OA progression to total hip replacement: can we do better than risk
      factors alone using active shape modelling as an imaging biomarker?
AB  - OBJECTIVE: Previously, active shape modelling (ASM) of the proximal femur was
      shown to identify those individuals at highest risk of developing radiographic
      OA. Here we determine whether ASM predicts the need for total hip replacement
      (THR) independent of Kellgren-Lawrence grade (KLG) and other known risk factors.
      METHODS: A retrospective cohort study of 141 subjects consulting primary care
      with new hip pain was conducted. Pelvic radiographs taken on recruitment were
      assessed for KLG, centre-edge angle, acetabular depth and femoral head migration.
      Clinical factors (duration of pain, use of a stick and physical function) were
      collected by self-completed questionnaires. ASM differences between shape mode
      scores at baseline for individuals who underwent THR during the 5-year follow-up
      (n = 27) and those whose OA did not progress radiographically (n = 75) were
      compared. RESULTS: A 1 s.d. reduction in baseline ASM mode 2 score was associated
      with an 81% reduction in odds of THR (OR = 0.19, 95% CI 0.52, 0.70) after
      adjustment for KLG, radiographic and clinical factors. A similar reduction in
      odds of THR was associated with a 1 s.d. reduction in mode 3 (OR = 0.45, 95% CI
      0.28, 0.71) and a 1 s.d. increase in mode 4 score (OR = 2.8, 95% CI 1.7, 4.7),
      although these associations were no longer significant after adjustment for KLG
      and clinical factors. CONCLUSION: ASM of the hip joint is a reliable early
      biomarker of radiographic OA severity, which can improve the ability to identify
      patients at higher risk of rapid progression and poor outcome even when KLG and
      clinical risk factors are taken into account.

PMID- 22139533
TI  - uPAR regulates bronchial epithelial repair in vitro and is elevated in asthmatic
      epithelium.
AB  - BACKGROUND: The asthma-associated gene urokinase plasminogen activator receptor
      (uPAR) may be involved in epithelial repair and airway remodelling. These
      processes are not adequately targeted by existing asthma therapies. A fuller
      understanding of the pathways involved in remodelling may lead to development of
      new therapeutic opportunities. uPAR expression in the lung epithelium of normal
      subjects and patients with asthma was investigated and the contribution of uPAR
      to epithelial wound repair in vitro was studied using primary bronchial
      epithelial cells (NHBECs). METHODS: Bronchial biopsy sections from normal
      subjects and patients with asthma were immunostained for uPAR. NHBECs were used
      in a scratch wound model to investigate the contribution of the plasminogen
      pathway to repair. The pathway was targeted via blocking of the interaction
      between urokinase plasminogen activator (uPA) and uPAR and overexpression of
      uPAR. The rate of wound closure and activation of intracellular signalling
      pathways and matrix metalloproteinases (MMPs) were measured. RESULTS: uPAR
      expression was significantly increased in the bronchial epithelium of patients
      with asthma compared with controls. uPAR expression was increased during wound
      repair in monolayer and air-liquid interface-differentiated NHBEC models.
      Blocking the uPA-uPAR interaction led to attenuated wound repair via changes in
      Erk1/2, Akt and p38MAPK signalling. Cells engineered to have raised levels of
      uPAR showed attenuated repair via sequestration of uPA by soluble uPAR.
      CONCLUSIONS: The uPAR pathway is required for efficient epithelial wound repair.
      Increased uPAR expression, as seen in the bronchial epithelium of patients with
      asthma, leads to attenuated wound repair which may contribute to the development
      and progression of airway remodelling in asthma. This pathway may therefore
      represent a potential novel therapeutic target for the treatment of asthma.

PMID- 22139535
TI  - Sustained cytoplasmic delivery and anti-viral effect of PLGA nanoparticles
      carrying a nucleic acid-hydrolyzing monoclonal antibody.
AB  - PURPOSE: Cytoplasmic delivery of a monoclonal antibody (mAb) with nucleic acid
      hydrolyzing activity (3D8 scFv) using poly(lactic-co-glycolic acid) nanoparticles
      (PLGA NPs) was investigated for persistent anti-viral effect. METHODS: 3D8 scFv
      loaded PLGA (3D8-PLGA) NPs were prepared via a double emulsion method that was
      previously optimized. Flow cytometry and confocal microscopy was carried out to
      confirm the cellular uptake and cytoplasmic localization. immunochemical and
      fluorescence resonance energy transfer (FRET) assays tested the cytoplasmic
      release and hydrolyzing effect of 3D8 scFv, respectively. Anti-viral activity
      test was performed using MTT assay with vesicular stomatitis virus (VSV)-infected
      HeLa cells. RESULTS: 3D8-PLGA NPs were much more effectively taken into cells in
      dose- and time-dependent manner and localized in the cytosolic region, compared
      to free 3D8 scFv. 3D8 scFv was released and hydrolyzed RNAs in the cytoplasm,
      exhibiting the maxima at a period of time (12-24 h). Anti-viral activity test
      revealed that 3D8-PLGA NP has dose- and time-dependent anti-viral effect and the
      maximum effect at the dose of 2 mg/ml and the incubation of 3 days. CONCLUSIONS:
      Cytoplasmic delivery of 3D8 scFv via PLGA NPs could enhance the viability of
      infected cells in sustained manner due to preserved activity, much improved
      cellular uptake and sustained release.

PMID- 22139534
TI  - Apigenin attenuates insulin-like growth factor-I signaling in an autochthonous
      mouse prostate cancer model.
AB  - PURPOSE: Deregulation of IGF signaling plays an important role in prostate cancer
      and contributes to invasion and metastasis. We determined the effect of apigenin,
      a plant flavone, on IGF signaling and its downstream targets in TRAMP mice.
      METHODS: Mice received p.o. apigenin at 20 and 50 MUg/day dose for 20 weeks.
      ELISA, Western blotting and immunohistochemistry were performed to examine the
      IGF-axis and its regulated pathway in response to apigenin intake. RESULTS:
      Increased serum levels of IGF-I, VEGF, uPA and concomitant decrease in IGFBP-3
      were observed; p-Akt (Ser473), p-ERK1 (T202/Y204) and p-ERK2 (T185/Y187)
      expression increased in the dorso-lateral prostate of TRAMP mice during the
      course of cancer progression as a function of age. P.o. administration of
      apigenin resulted in substantial reduction in the levels of IGF-I and increase in
      the levels of IGFBP-3 in the serum and the dorso-lateral prostate. This
      modulation of IGF/IGFBP-3 was associated with an inhibition of p-Akt and p
      ERK1/2. Apigenin intake resulted in marked inhibition of VEGF, uPA, MMP-2 and MMP
      9 which coincided with tumor growth inhibition and complete absence of metastasis
      in TRAMP mice. CONCLUSIONS: Our results indicate that apigenin effectively
      suppressed prostate cancer progression in TRAMP mice by attenuating IGF-I/IGFBP-3
      signaling and inhibiting angiogenesis and metastasis.

PMID- 22139536
TI  - MR molecular imaging of prostate cancer with a peptide-targeted contrast agent in
      a mouse orthotopic prostate cancer model.
AB  - PURPOSE: To study the effectiveness of a peptide targeted nanoglobular Gd-DOTA
      complexes for MR molecular imaging of prostate cancer in a mouse orthotopic PC-3
      prostate cancer model. METHODS: A CLT1 (CGLIIQKNEC) peptide-targeted generation 2
      nanoglobular Gd-DOTA monoamide conjugate [CLT1-G2-(Gd-DOTA)] was used for imaging
      fibrin-fibronectin complexes in prostate tumor using a non-specific peptide KAREC
      modified conjugate, KAREC-G2-(Gd-DOTA) as a control. Cy5 conjugates of CLT1 and
      KAREC were synthesized for binding studies. Orthotopic PC-3 prostate tumors were
      established in the prostate of athymic male nude mice. MRI study was performed on
      a Bruker 7T small animal MRI system. RESULTS: CLT1 peptide showed specific
      binding in the prostate tumor with no binding in normal tissues. The control
      peptide had little binding in normal and tumor tissues. CLT1-G2-(Gd-DOTA)
      resulted in stronger contrast enhancement in tumor tissue than KAREC-G2-(Gd
      DOTA). CLT1-G2-(Gd-DOTA) generated ~100% increase in contrast-to-noise ratio
      (CNR) in the tumor compared to precontrast CNR at 1 min post-injection, while
      KAREC-G2-(Gd-DOTA) resulted in 8% increase. CONCLUSION: CLT1-G2-(Gd-DOTA) is a
      promising molecular MRI contrast agent for fibrin-fibronectin complexes in tumor
      stroma. It has potential for diagnosis and assessing prognosis of malignant
      tumors with MRI.

PMID- 22139537
TI  - Preparation and evaluation of oleoyl-carboxymethy-chitosan (OCMCS) nanoparticles
      as oral protein carriers.
AB  - Oleoyl-carboxymethy chitosan (OCMCS) nanoparticles based on chitosan with
      different molecular weights (50, 170 and 820 kDa) were prepared by self-assembled
      method. The nanoparticles had spherical shape, positive surface charges and the
      mean diameters were 157.4, 274.1 and 396.7 nm, respectively. FITC-labeled OCMCS
      nanoparticles were internalized via the intestinal mucosa and observed in liver,
      spleen, intestine and heart following oral deliverance to carps (Cyprinus
      carpio). Extracellular products (ECPs) of Aeromonas hydrophila as microbial
      antigen was efficiently loaded to form OCMCS-ECPs nanoparticles and shown to be
      sustained release in PBS. Significantly higher (P < 0.05) antigen-specific
      antibodies were detected in serum after orally immunized with OCMCS-ECPs
      nanoparticles than that immunized with ECPs alone and non-immunized in control
      group in carps. These results implied that amphiphilic modified chitosan
      nanoparticles had great potential to be applied as carriers for the oral
      administration of protein drugs.

PMID- 22139538
TI  - Complementary and alternative medicine in the treatment of menopausal symptoms.
AB  - A large number of women will pass through menopause each year. Women in
      menopausal transition experience a variety of menopausal symptoms. Although
      hormonal therapy remains the most effective treatment, side effects have been
      reported by several large studies. An increased number of women seek the use of
      complementary and alternative medicine (CAM) for treating menopausal symptoms.
      This review analyzes the evidence from systematic reviews, randomized controlled
      trials and epidemiological studies of using herbal medicine (Black cohosh, Dong
      quai, St John's wart, Hops, Wild yam, Ginseng, and evening primrose oil) and
      acupuncture for the treatment of menopausal symptoms. Evidence supporting the
      efficacy and safety of most CAM for relief of menopausal symptoms are limited.
      Future larger and better controlled studies testing the effectiveness of these
      treatments are needed.

PMID- 22139539
TI  - Chinese medicine for menopausal syndrome: current status, problems and
      strategies.
AB  - The use of Chinese medicine (CM) for the management of: menopausal syndrome is
      considered effective both at home and abroad, and more and more clinical studies
      are confirming its efficacy. However, many problems still exit in current
      studies, such as the standard of CM syndrome differentiation, the design
      methodology and criteria to assess the quality of clinical trials and the
      efficacy of interventions. In this paper, the authors present the CM research and
      treatment strategies for menopausal syndrome with concepts explaining the CM
      understanding of the mechanism of the disorder. It is concluded that CM is
      effective for menopausal syndrome, but improvement in both study methodology and
      treatment strategy is needed. In detail, it is firstly necessary to conduct
      clinical studies to evaluate the difference of various CM treatments for
      menopausal syndrome manifesting different symptoms, so as to establish a
      comprehensive treatment protocol of CM. Secondly, an acknowledged evaluation
      system needs to be founded, which embodies the characteristics of CM, and covers
      appropriate endpoint indices and parameters to objectively evaluate the effect
      and study quality of CM. Finally, an epidemiological survey with large sample
      size should be implemented with robust statistical design and CM expertise to
      collect data for establishing diagnostic criteria for menopause in different
      stages and with different symptoms.

PMID- 22139540
TI  - Perspectives in clinical research of acupuncture on menopausal symptoms.
AB  - Seventy percentage of perimenopausal and early postmenopausal women will
      experience menopause symptoms. Primary menopause symptoms in Western countries
      included hot flashes, insomnia, somatic pain, depression, and fatigue. Hot
      flashes were most commonly treated. Menopausal hormone replacement therapy (HRT)
      continues to have a clinical role in the management of vasomotor symptoms, but
      since 2002 there has been a marked global decline in its use due to concerns
      about the risks and benefits of HRT; consequently many women with menopause
      symptoms are now seeking alternatives including acupuncture. Acupuncture has a
      long tradition of use for the treatment of different menopause symptoms. Its
      effectiveness has been studied for natural menopause or chemical and surgery
      induced menopause. Here we provide an update on recent advances in the field for
      clinicians. The recent systematic reviews on acupuncture in menopausal symptoms
      suggest that acupuncture is an effective and valuable option for women suffering
      from menopause. However, the science of acupuncture therapies is still inadequate
      to sufficiently support the benefits of acupuncture therapies. Finally, we
      discuss our points of view on clinical trials of acupuncture for menopause
      symptoms.

PMID- 22139541
TI  - Serum low-density lipoprotein and heart rate related to the effectiveness in the
      treatment of angina pectoris with two similar Chinese medicine herbal formulae.
AB  - OBJECTIVE: To explore the effectiveness related indicators which might help
      identify the indications of Tongxinluo Capsule () and Kangxin Capsule ()
      targeting on qi deficiency and blood stasis pattern in Chinese medicine (CM) in
      the treatment of angina pectoris. METHODS: The data from a multicenter,
      randomized and double-blinded study conducted at 5 centers in China were obtained
      for the analysis. A total of 239 patients with angina pectoris and CM syndrome of
      qi deficiency and blood stasis were randomly assigned in a 1:1 ratio to
      Tongxinluo Capsule group (119 cases) and Kangxin Capsule group (120 cases).
      Angina effectiveness and electrocardiogram (ECG) improvement were selected as the
      therapeutic outcomes. RESULTS: After a 4-week treatment, the effective rates of
      Tongxinluo Capsule and Kangxin Capsule were 43.70% and 25.00%, respectively (P
      <0.05). Serum low-density lipoprotein (LDL) level was found to influence the
      effectiveness of Tongxinluo Capsule which had higher effective rate in the
      patients with lower level of LDL. Heart rate was found to influence the
      effectiveness in the patients treated with Kangxin Capsule which had higher
      effective rate in the patients with heart rate [Symbol: see text]80 beats/min.
      CONCLUSION: LDL level and heart rate were the indicators which help indentify the
      indications of Tongxinluo Capsule and Kangxin Capsule, respectively, in the
      treatment of angina pectoris with CM syndrome of qi deficiency and blood stasis.

PMID- 22139542
TI  - In vitro and in vivo inhibitory effect of the combination of Wenxia Changfu
      formula [see text] with cisplatin in non-small cell lung cancer.
AB  - OBJECTIVE: To observe the effect of the combination of Wenxia Changfu Formula
      ([see text], WCF) with cisplatin (CDDP) on inhibiting non-small cell lung cancer
      (NSCLC) in vitro and In Vivo and explore its mechanism from its effect on cell
      cycle. METHODS: In vitro, WCF-containing serum was prepared and the rhubarb b1,
      emodin, and aconitine were detected qualitatively by high-performance liquid
      chromatogram (HPLC). A549 cell lines were treated with blank control (dimethyl
      sulfoxide), normal serum, normal serum with CDDP (1.25, 2.5, and 5.0 MUg/mL,
      respectively), WCF-containing serum plus different doses of CDDP (1.25, 2.5, and
      5.0 MUg/mL, respectively). The inhibitory effect was detected by 3-(4,5)
      dimethylthiazo(-zy1)-3,5-diphenylterazolium bromide (MTT). The cell cycle was
      detected by flow cytometry. The protein and mRNA expressions of cyclin D1,
      proliferating cell nuclear antigen (PCNA), retinoblastoma (Rb), and p16 were
      observed with immunofluorescence and RT-PCR, respectively. In Vivo, nude mice
      xenograft model was established and grouped into the control, CDDP, WCF, and
      combination groups. The combination's inhibition of tumor growth and influence on
      the weight, spleen, and thymus gland were observed. RESULTS: The inhibitory rate
      of the combination against A549 cell lines excelled the CDDP alone significantly
      (P <0.05); the combination showed a synergism inhibitory effect (Q=1.19).
      Compared with the monotherapy, the combination increased the cell percentage in
      G(0)/G(1) phase and decreased the cell percentage in S phase significantly (P
      <0.05); the protein and mRNA expressions of cyclin D1, PCNA, and Rb were
      significantly reduced; the protein and mRNA expressions of p16 were significantly
      enhanced. Compared with the monotherapy, the combination inhibited the tumor
      growth significantly In Vivo and reduced the weight of tumor (P <0.05); compared
      with the CDDP group, the spleen and thymus gland index of the combination group
      were enhanced significantly (P <0.05). CONCLUSIONS: The combination of WCF with
      CDDP significantly inhibited the A549 cell lines proliferation in vitro and the
      growth of the tumor In Vivo; it inhibited effectively the atrophy of the immune
      organ caused by chemotherapy. The combination inhibited overproliferation of A549
      cell lines by arresting the G(0) /G(1) phase of cell cycle and affecting the
      protein and mRNA expressions of cell cycle-related proteins, cyclin D1, etc.

PMID- 22139543
TI  - Efficacy of dual antiplatelet therapy combined with Naoxintong capsules [see
      text] following coronary microembolization induced by homologous microthrombi in
      rats.
AB  - OBJECTIVE: To evaluate the effificacy of dual antiplatelet therapy combined with
      Naoxintong Capsule ([see text], NXTC) in a rat model of coronary
      microembolization (CME). METHODS: A total of 95 rats were randomly divided into 6
      groups: control, sham-operation, CME model, NXTC, dual antiplatelet (clopidogrel
      and aspirin) intervention (DA), and NXTC combined with DA (NDA) groups. The
      complete data in 69 rats were obtained. The number of CME, myocardial apoptosis
      rate, bleeding time, clotting time, and adensosine diphosphate (ADP)-induced
      platelet aggregation were assessed. RESULTS: Compared with the CME group, the
      number of CME and myocardial apoptosis rates were signifificantly decreased in
      the NXTC, DA, and NDA groups (P <0.01). Compared with other intervention groups,
      the number of CME and myocardial apoptosis rates were the least in the NDA group
      (P <0.01), and the incidence of surgical bleeding was the highest in the DA group
      (P <0.01). Compared with the CME group, ADP-induced maximum platelet aggregation
      rate was significantly inhibited in the NXTC, DA, and NDA groups (P <0.01), both
      bleeding time and clotting time were signifificantly increased in the NXTC, DA,
      and NDA groups (P <0.01), while the above parameters were the highest in the DA
      group (P <0.05). CONCLUSION: The combination therapy of NXTC and DA enhanced the
      anti-CME effect of either therapy alone and reduced the risk of the DA therapy
      associated bleeding, demonstrating an improved benefifit/ risk ratio in the rat
      model of CME.

PMID- 22139544
TI  - Anti-obesity effects of Chang-Chul-Eui-Ee-In-Tang [see text] in female rats with
      diet-induced obesity.
AB  - OBJECTIVE: To investigate the effects of Chang-Chul-Eui-Ee-In-Tang ([see text],
      CCEET), modififi ed CCEET (MCCEET), and Semen Coicis (SC, a major component of
      CCEET) on energy and glucose homeostasis. The possible mechanism of action of
      CCEET was also determined. METHODS: A total of 100 Sprague Dawley female rats
      were randomly assigned to 5 groups, with 20 in each group. Rats in 4 groups were
      fed with a high fat diet supplementation (2 g/kg body weight), and water extracts
      of CCEET, MCCEET, SC, and cellulose (negative control), respectively. The last
      group was fed with a low-fat diet as a positive control. RESULTS: CCEET and
      MCCEET decreased body weight and body fat (mesenteric and retroperitoneal fat)
      more than SC. This decrease was due to decreased energy intake and increased
      energy expenditure and fat oxidation. The improvement in energy homeostasis was
      associated with the enhancement of the hypothalamic leptin signalling pathway
      involving potentiating the phosphorylation of the signal transducer and activator
      of transcription-3, as well as attenuating the phosphorylation of 5' adenosine
      monophosphate-activated protein kinase (AMPK). Both CCEET and MCCEET improved
      glucose tolerance without changing serum insulin levels during an oral glucose
      tolerance test but MCCEET had a better effect than CCEET. CONCLUSIONS: Both CCEET
      and MCCEET safely exerted anti-obesity effects by enhancing energy balance in
      female rats with diet-induced obesity; MCCEET showed a better effect on glucose
      homeostasis.

PMID- 22139545
TI  - Clinical evaluation of oral Fructus bruceae oil combined with radiotherapy for
      the treatment of esophageal cancer.
AB  - OBJECTIVE: To evaluate the therapeutic efficacy and side effects of oral Fructus
      bruceae oil combined with radiotherapy in the treatment of esophageal cancer.
      METHODS: A total of 80 patients with esophageal cancer were equally and randomly
      divided into two groups. The patients in Group A were treated with radiotherapy
      (60-65 Gy, 6-7 weeks) and oral Fructus bruceae oil (20 mL, 3 times per day for 12
      weeks), while the patients in Group B were treated with radiotherapy alone. The
      short-term effect was evaluated by Response Evaluation Criteria in Solid Tumors
      (RECIST) and quality of life (QOL) was evaluated by the Karnofsky scoring (KFS).
      The outcome measures included complete remission (CR) rate, partial remission
      (PR) rate, effective rate as CR+PR, patients' QOL and adverse effects. RESULTS:
      After 12-week treatment, the CR and CR+PR were significantly higher in Group A
      than those in Group B (P <0.05). There was an improvement in esophageal
      obstruction of 87.5% and 60.0%, respectively, and in KFS of 84.6% and 43.9%,
      respectively, in Groups A and B. CONCLUSION: Oral medication with oral Fructus
      bruceae oil could effectively improve the efficacy of radiotherapy in esophageal
      cancer, including a reduction in esophageal obstruction, and also reduce the side
      effects of radiotherapy; thus it would be very promising for clinical
      application.

PMID- 22139546
TI  - Red ginseng for type 2 diabetes mellitus: a systematic review of randomized
      controlled trials.
AB  - OBJECTIVE: Red ginseng (RG, Panax ginseng C.A. Meyer) is one of the widely used
      herbs for treating type 2 diabetes mellitus (DM). However, no systematic review
      of the effectiveness of RG for type 2 DM is available. This systematic review
      aimed to evaluate the current evidence for the effectiveness of RG in patients
      with type 2 DM. METHODS: Electronic searches of 14 electronic databases were
      conducted without language restrictions. All randomized clinical trials (RCTs)
      with RG as a treatment for type 2 DM were considered for inclusion. Their
      methodological quality was assessed using the Cochrane criteria. RESULTS: Four
      RCTs met our inclusion criteria. Their methodological quality was variable. Three
      of the RCTs compared the effectiveness of RG with placebo. The meta-analysis of
      these data failed to favor RG over placebo for fasting plasma glucose (FPG) [n
      =76, weighted mean difference (WMD): -0.43 mmol/L; 95% confidence interval (CI): 
      1.16 to 0.30, =0.25] and fasting plasma insulin (FPI) (n =76, WMD: -8.43 pmol/L;
      95% CI: -19.54 to 2.68, P =0.14) for 12 weeks of treatment. One RCT compared the
      effects of RG with no treatment. The results did not suggest favorable effects of
      RG on FPG, hemoglobin A(1c) (HbA(1c)) or 2-h blood glucose after a meal (PP2h).
      CONCLUSIONS: The evidence for the effectiveness of RG in controlling glucose in
      type 2 DM is not convincing. Few included studies with various treatment regimens
      prohibit definitive conclusions. More rigorous studies are needed to clarify the
      effects of RG on this condition.

PMID- 22139547
TI  - Initiating Hehe [see text] medical system of traditional Chinese medicine and
      biomedicine to realize health cycle of human beings.
AB  - This paper suggests a novel approach concerning the medical treatment of human
      beings, which appears to be economically and practically superior to either
      biomedicine or traditional medicine. A brand new medical system-Hehe [see text]
      medicine, has been proposed based on a preventive-biomedical-psycho-social
      treatment model. This is characterized by a dual approach in which life nurturing
      is consistently practised and medical treatment is applied when necessary in
      order to maintain a healthy life. Its core value would facilitate the self
      restoration to health and self-adaptation to nature through health cultivation
      and medical means. Medical services would be firstly provided to the prevention
      of potential disease germinating in the human body, and clinical medical
      treatment would be the last resort of systematic medical practice. This paper
      discusses not only this new concept but also the advantages of traditional
      Chinese medicine and biomedicine, especially how both medical systems compare in
      cognitive style, on a cultural level, and on a technical level.

PMID- 22139548
TI  - The empiric use of palm kernel oil in neonatal skin care: justifiable or not?
AB  - Palm kernel oil is a vegetable oil derived from Elaeis guineensis and widely used
      in neonatal settings for skin care. It is a good emollient with a beneficial
      effect in moisturizing the skin and preventing transdermal heat and water loss.
      However, it's putative roles in the prevention or treatment of fatty acid
      defificiency is still controversial. So is its function in the improvement of
      neurological development from its longchain polyunsaturated fatty acids? We set
      out in this review to verify whether its empiric use in this context has any
      scientific justification and is recommendable. Although there is evidence that it
      has emollient and moisturizing properties necessary for softening the skin and
      restoring elasticity, controversy subsists on its other nutritional and
      neurodevelopmental properties.

PMID- 22139549
TI  - Pulmonary arterial hypertension in the setting of pregnancy: a case series and
      standard treatment approach.
AB  - Pregnancy in patients with pulmonary arterial hypertension (PAH) is associated
      with a maternal mortality of 30-50% despite modern treatment modalities. The
      majority of maternal deaths in PAH patients occur either during labor and
      delivery or within 1 month postpartum. Cardiovascular collapse is attributed to a
      mismatch between the physiologic limitations of PAH and the changes that occur
      with pregnancy and delivery. In the Unites States, there is no consensus on the
      management of PAH in pregnancy. Several case reports have been published
      describing improved maternal-fetal outcomes, likely due to new advanced PH
      therapies, earlier diagnosis of PAH, and an adoption of a multidisciplinary
      treatment approach. We present five cases of gravid PAH patients successfully
      managed at our institution with a description of our standardized
      multidisciplinary treatment approach.

PMID- 22139550
TI  - Cough variant asthma: lessons learned from deep inspirations.
AB  - The pathophysiology of cough variant asthma is poorly understood. In particular,
      the mechanisms that cause different symptoms in typical asthma (in which wheeze
      predominates) compared with cough variant asthma (in which cough predominates)
      have not been determined. Traditional explanations include higher wheezing
      thresholds, differences in cough sensitivity, and/or differences in small airway
      function. Recent studies using high-dose methacholine challenge testing suggest
      that altered small-airway function plays a role. Preservation or loss of the
      bronchoprotective effect of a deep inspiration may be a fundamental
      pathophysiologic difference between asthma, cough variant asthma, methacholine
      induced cough with normal sensitivity, and eosinophilic bronchitis.

PMID- 22139551
TI  - Cough reflex in lung transplant recipients.
AB  - Lung transplantation has become the standard of care for particular individuals
      with advanced lung disease. However, this surgical procedure involves
      interruption of the lower vagal nerve fibers which leads to loss of the
      protective cough reflex. Injury of the neural pathways involved with the sensory
      limb of the cough reflex is associated with an increased risk of complications
      involving the allograft. While loss of the cough reflex was once considered
      permanent, recent evidence indicates functional and structural restoration is a
      time-dependent process that occurs 6-12 months after lung transplantation. The
      implication that the cough reflex may be reestablished in lung transplant
      recipients provides insight into the dynamic response to airway neural injury
      that may lead to improvements in allograft tissue repair.

PMID- 22139552
TI  - Usefulness of 18F-FDG uptake with clinicopathologic and immunohistochemical
      prognostic factors in breast cancer.
AB  - INTRODUCTION: The aim of this study was to analyze the clinical significance of
      maxSUV with clinicopathologic and immunohistochemical prognostic factors in
      patients with primary breast cancer. METHODS: Ninety-one women (48.5 +/- 11.2
      years of age) with breast cancer who underwent (18)F-FDG PET (PET) before surgery
      were recruited. All of the breast cancers were invasive ductal carcinomas and >=1
      cm in size to exclude a partial volume effect. The maxSUV of breast cancers was
      compared with histopathologic and immunohistochemical findings. Additionally, the
      ability of PET to discriminate axillary nodal status (ANS) and correlation
      between ANS and tumor characteristics were evaluated. RESULTS: A high maxSUV of
      breast cancer was significantly correlated with the following poor prognosis
      factors: tumor invasiveness >2 cm (2.9 vs. 5.4; p < 0.001); high score of nuclear
      (3.5 vs. 5.3; p = 0.008) or histologic grade (3.3 vs. 5.5; p < 0.001); MIB-1
      >=10% (3.0 vs. 4.9; p < 0.002); ER-negativity (4.8 vs. 3.8; p = 0.019); PR
      negativity (5.0 vs. 3.6; p = 0.029); and triple negativity (ER-, PR-, and c-erbB
      2-negative; 5.3 vs. 3.8; p < 0.016). MaxSUV was not affected by menopausal
      status, ANS, lymphovascular invasion, including CD34 and D2-40 (LVIs), p53, and c
      erbB-2 status. Additionally, the sensitivity and specificity of PET for
      discriminating ANS were 51.1 and 97.8%, respectively. ANS was correlated with
      tumor invasiveness >2 cm (p = 0.046), LVIs (all of variables; p < 0.001), and
      triple negativity (p = 0.049). CONCLUSIONS: A high FDG uptake of breast tumor is
      correlated with several poor prognosis factors, such as tumor invasiveness >2 cm,
      higher tumor grade, higher MIB-1, hormonal receptor negativity, and triple
      negativity. However, PET has a limited value in discriminating axillary lymph
      nodes. Pre-operative PET is a useful modality to predict biologic poor prognosis
      factors which could affect adjunctive therapy of breast cancer.

PMID- 22139553
TI  - Resuscitative emergency thoracotomy in a Swiss trauma centre.
AB  - BACKGROUND: Resuscitative emergency thoracotomy (ET) is performed as a salvage
      manoeuvre for selected patients with trauma. However, reports from European
      trauma centres are scarce. METHODS: A retrospective analysis was undertaken of
      injured patients who underwent resuscitative ET in the emergency department (ED)
      or operating room (OR) between January 1996 and September 2008. Survival in the
      ED and to hospital discharge was analysed using logistic regression. RESULTS:
      During the study interval 121 patients required a resuscitative thoracotomy, of
      which 49 (40.5 per cent) were performed in the ED and 72 (59.5 per cent) in the
      OR. Patients in the OR had higher blood pressure on arrival (median 110 versus 60
      mmHg; P < 0.001), were less often in severe haemorrhagic shock (63 versus 94 per
      cent; P < 0.001), had fewer serious head injuries (Abbreviated Injury Score of 3
      or above in 33 versus 53 per cent; P = 0.031) and more often had a penetrating
      stab wound as the dominating mechanism (25 versus 10 per cent; P = 0.042)
      compared with those in the ED. Ten patients (20 per cent) survived to hospital
      discharge after ED thoracotomy, compared with 53 (74 per cent) of those treated
      in the OR. Penetrating injury and Glasgow Coma Scale score above 8 were
      independent predictors of hospital survival following ED thoracotomy. No patient
      with a blunt injury and no detectable signs of life on admission survived. Three
      of 26 patients with blunt trauma and signs of life on admission survived to
      hospital discharge. CONCLUSION: Resuscitative ET may be life-saving in selected
      patients. Location of the procedure is dictated by injury severity and vital
      parameters. Outcome is best when signs of life are present on admission, even for
      blunt injuries.

PMID- 22139555
TI  - Determining genetic risk factors for pediatric type 2 diabetes.
AB  - The prevalence of type 2 diabetes (T2D) is increasing significantly in the
      pediatric population. A strong family history of the disease suggests the
      involvement of genetic factors for diabetes development, but defining the
      molecular genetics of T2D in children is difficult due to a low number of
      subjects and the lack of robust diagnostic criteria. Thus, genetic studies of T2D
      have been carried out almost exclusively in adults. In this review, the genetics
      of T2D is summarized and options for discovering the missing heritability
      explored. The review concludes with a discussion of future research that will be
      required for determining genetic risk factors for pediatric T2D.

PMID- 22139554
TI  - Hypoxia-derived oxidative stress mediates epigenetic repression of PKCepsilon
      gene in foetal rat hearts.
AB  - AIMS: Hypoxia causes protein kinase C epsilon (PKCepsilon) gene repression in
      foetal hearts, resulting in heightened cardiac susceptibility to ischaemic injury
      in offspring. We tested the hypothesis that hypoxia inducible factor 1 (HIF-1)
      and/or reactive oxygen species (ROS) mediate hypoxia-induced PKCepsilon gene
      repression. METHODS AND RESULTS: Hypoxia induced in vivo to pregnant rats, ex
      vivo to isolated foetal rat hearts, and in vitro in the rat embryonic ventricular
      myocyte cell line H9c2 resulted in a comparable decrease in PKCepsilon protein
      and mRNA abundance in foetal hearts and H9c2 cells, which was associated with a
      significant increase in CpG methylation of the SP1-binding sites at the
      PKCepsilon promoter. In H9c2 cells and foetal hearts, hypoxia caused nuclear
      accumulation of HIF-1alpha, which was inhibited by 3-(5'-hydroxymethyl-2'-furyl)
      1-benzylindazole and 2-methoxy estradiol. The HIF-1alpha inhibitors had no
      significant effect on hypoxia-induced PKCepsilon mRNA repression. Hypoxia
      produced a time-dependent increase in ROS production in H9c2 cells and foetal
      hearts that was blocked by ROS scavengers N-acetyl-cysteine or tempol. In
      accordance, N-acetyl-cysteine and tempol, but not apocynin, inhibited the hypoxic
      effect and restored PKCepsilon protein and mRNA expression to the control values
      in foetal hearts and H9c2 cells. The ROS scavengers blocked hypoxia-induced CpG
      methylation of the SP1-binding sites, restored SP1 binding to the PKCepsilon
      promoter, and abrogated the hypoxia-induced increase in the susceptibility of the
      heart to ischaemic injury in offspring. CONCLUSIONS: The results demonstrate that
      hypoxia induces epigenetic repression of the PKCepsilon gene through a NADPH
      oxidase-independent ROS-mediated pathway in the foetal heart, leading to
      heightened heart vulnerability to ischaemic injury in offspring.

PMID- 22139556
TI  - Type 2 diabetes in childhood: clinical characteristics and role of beta-cell
      autoimmunity.
AB  - The global obesity epidemic has led to dramatic increases in the incidence and
      prevalence of type 2 diabetes mellitus (T2DM) among youth worldwide. In today's
      clinical practice it has become increasingly difficult to distinguish type 1
      diabetes mellitus (T1DM) from T2DM as many children with T1DM are overweight at
      diagnosis. Numerous recent publications note a significant proportion of
      physician-diagnosed T2DM youth with evidence of pancreatic autoimmunity,
      exemplifying the challenges in distinguishing between T1DM and T2DM. The clinical
      implications of the phenomenon of antibody positivity in phenotypic T2DM youth,
      also referred to as "type 1.5 diabetes" (T1.5 DM), "double diabetes," "latent
      autoimmune diabetes in youth" (LADY), and "hybrid diabetes," are unclear at
      present. Current and future work should determine if the presence of
      autoantibodies in phenotypic T2DM youth/children affects clinical course; this
      will facilitate the development of optimal treatment strategies.

PMID- 22139558
TI  - Proteins in human nutrition: review and recommendations of the Swiss Federal
      Commission for Nutrition (FCN) 2011.

PMID- 22139557
TI  - Management of diabetes in pregnancy.
AB  - The link between diabetes and poor pregnancy outcomes is well established. As in
      the non-pregnant population, pregnant women with diabetes can experience profound
      effects on multiple maternal organ systems. In the fetus, morbidities arising
      from exposure to diabetes in utero include not only increased congenital
      anomalies, fetal overgrowth, and stillbirth, but metabolic abnormalities that
      appear to carry on into early life, adolescence, and beyond. This article
      emphasizes the newest guidelines for diabetes screening in pregnancy while
      reviewing their potential impact on maternal and neonatal complications that
      arise in the setting of hyperglycemia in pregnancy.

PMID- 22139559
TI  - Dietary proteins in humans: basic aspects and consumption in Switzerland.
AB  - This introductory review gives an overview on protein metabolism, and discusses
      protein quality, sources, and requirements as well as the results from recent
      studies on Swiss spontaneous protein consumption. To assess protein quality in
      protein mixes and foods, the "protein digestibility-corrected amino acid score"
      (PDCAAS) is presented as a valuable tool in addition to the biological value
      (BV). Considering protein intake recommendations, the lower limit recommended has
      been defined according to the minimal amount needed to maintain short-term
      nitrogen balance in healthy people with moderate activity. Evaluation of intakes
      in Switzerland from food consumption data is about 90 g/day of protein per
      person. Two-thirds of proteins consumed in Switzerland are animal proteins with
      high biological value [meat and meat products (28 %), milk and dairy products (28
      %), fish (3 %), and eggs (3 %)] and about 1/3 of proteins are of plant origin (25
      % of cereals, 3 - 4 % of vegetables). Actual spontaneous protein consumption in
      Switzerland by specific groups of subjects is well within the actual
      recommendations (10 - 20 % of energy) with only the frail elderly being at risk
      of not covering their requirements for protein.

PMID- 22139560
TI  - Protein turnover, ureagenesis and gluconeogenesis.
AB  - The major processes discussed below are protein turnover (degradation and
      synthesis), degradation into urea, or conversion into glucose (gluconeogenesis,
      Figure 1). Daily protein turnover is a dynamic process characterized by a double
      flux of amino acids: the amino acids released by endogenous (body) protein
      breakdown can be reutilized and reconverted to protein synthesis, with very
      little loss. Daily rates of protein turnover in humans (300 to 400 g per day) are
      largely in excess of the level of protein intake (50 to 80 g per day). A fast
      growing rate, as in premature babies or in children recovering from malnutrition,
      leads to a high protein turnover rate and a high protein and energy requirement.
      Protein metabolism (synthesis and breakdown) is an energy-requiring process,
      dependent upon endogenous ATP supply. The contribution made by whole-body protein
      turnover to the resting metabolic rate is important: it represents about 20 % in
      adults and more in growing children. Metabolism of proteins cannot be
      disconnected from that of energy since energy balance influences net protein
      utilization, and since protein intake has an important effect on postprandial
      thermogenesis - more important than that of fats or carbohydrates. The metabolic
      need for amino acids is essentially to maintain stores of endogenous tissue
      proteins within an appropriate range, allowing protein homeostasis to be
      maintained. Thanks to a dynamic, free amino acid pool, this demand for amino
      acids can be continuously supplied. The size of the free amino acid pool remains
      limited and is regulated within narrow limits. The supply of amino acids to cover
      physiological needs can be derived from 3 sources: 1. Exogenous proteins that
      release amino acids after digestion and absorption 2. Tissue protein breakdown
      during protein turnover 3. De novo synthesis, including amino acids (as well as
      ammonia) derived from the process of urea salvage, following hydrolysis and
      microflora metabolism in the hind gut. When protein intake surpasses the
      physiological needs of amino acids, the excess amino acids are disposed of by
      three major processes: 1. Increased oxidation, with terminal end products such as
      CO2 and ammonia 2. Enhanced ureagenesis i. e. synthesis of urea linked to protein
      oxidation eliminates the nitrogen radical 3. Gluconeogenesis, i. e. de novo
      synthesis of glucose. Most of the amino groups of the excess amino acids are
      converted into urea through the urea cycle, whereas their carbon skeletons are
      transformed into other intermediates, mostly glucose. This is one of the
      mechanisms, essential for life, developed by the body to maintain blood glucose
      within a narrow range, (i. e. glucose homeostasis). It includes the process of
      gluconeogenesis, i. e. de novo synthesis of glucose from non-glycogenic
      precursors; in particular certain specific amino acids (for example, alanine), as
      well as glycerol (derived from fat breakdown) and lactate (derived from muscles).
      The gluconeogenetic pathway progressively takes over when the supply of glucose
      from exogenous or endogenous sources (glycogenolysis) becomes insufficient. This
      process becomes vital during periods of metabolic stress, such as starvation.

PMID- 22139561
TI  - Protein requirements in the elderly.
AB  - Adequate protein intake and the maintenance of nitrogen equilibrium are of
      particular importance in the elderly because this age group is at increased risk
      of illness and malnutrition. The current recommendation for protein intake of
      healthy elderly subjects is 0.8 g/kg body weight/day, the same as for younger
      adults. Nitrogen balance studies in the elderly, however, revealed conflicting
      results; some studies suggest that not all elderly can achieve a nitrogen balance
      with a protein intake of 0.8 g/kg body weight/day, particularly if energy supply
      is not adequate. Beyond the amount of protein needed for nitrogen balance, the
      optimal protein intake for preservation of lean body mass, body functions, and
      health is of paramount interest. At present, there is insufficient longer-term
      research with defined health outcomes to derive recommendations in this regard.
      Very little is also known about the protein needs of frail and unhealthy elderly.
      Until more evidence is available, it seems reasonable to ensure a protein intake
      of at least 0.8 g/kg body weight/day in all elderly persons, particularly in
      those at risk of malnutrition (e.g., frail and multimorbid elderly). In addition
      to ascertaining adequate protein and energy intake, physical activity should be
      encouraged in order to increase energy expenditure and food intake and to
      facilitate muscle protein anabolism.

PMID- 22139562
TI  - Role of dietary proteins in sports.
AB  - The previously separate dietary protein recommendations for strength and
      endurance athletes are no longer supported, and the daily intake for adult
      athletes suggested by most of the entities is about 1.5 g . kg(-1) body mass with
      a range of perhaps 1.0 to 2.0 g . kg(-1) body mass. This recommendation is a
      broad landmark that needs to be adapted to the individual circumstances of the
      athlete. Research of the past decade indicates a beneficial effect with respect
      to a positive net muscular protein balance if athletes ingest some protein before
      an exercise bout. The amount of protein to be ingested to elicit the highest
      benefit is about 10 to 20 g . h(-1), but due to the insufficient amount of
      available data, it is not possible yet to rank different protein types or sources
      according to their anabolic potential. A simple way to translate the nutrient
      based recommendations is the Swiss Food Pyramid for Athletes, which ensures a
      sufficient intake of energy, and all macro- and micronutrients in relation to the
      volume and intensity of the daily exercise.

PMID- 22139563
TI  - Dietary proteins in obesity and in diabetes.
AB  - Dietary proteins influence body weight by affecting four targets for body weight
      regulation: satiety, thermogenesis, energy efficiency, and body composition.
      Protein ingestion results in higher ratings of satiety than equicaloric amounts
      of carbohydrates or fat. Their effect on satiety is mainly due to oxidation of
      amino acids fed in excess; this effect is higher with ingestion of specific
      "incomplete" proteins (vegetal) than with animal proteins. Diet-induced
      thermogenesis is higher for proteins than for other macronutrients. The increase
      in energy expenditure is caused by protein and urea synthesis and by
      gluconeogenesis. This effect is higher with animal proteins containing larger
      amounts of essential amino acids than with vegetable proteins. Specifically, diet
      induced thermogenesis increases after protein ingestion by 20 - 30 %, but by only
      5 - 10 % after carbohydrates and 0 - 5 % after ingestion of fat. Consumption of
      higher amounts of protein during dietary treatment of obesity resulted in greater
      weight loss than with lower amounts of protein in dietary studies lasting up to
      one year. During weight loss and decreased caloric intake, a relatively increased
      protein content of the diet maintained fat-free mass (i. e. muscle mass) and
      increased calcium balance, resulting in preservation of bone mineral content.
      This is of particular importance during weight loss after bariatric surgery
      because these patients are at risk for protein malnutrition. Adequate dietary
      protein intake in diabetes type 2 is of specific importance since proteins are
      relatively neutral with regard to glucose and lipid metabolism, and they preserve
      muscle and bone mass, which may be decreased in subjects with poorly controlled
      diabetes. Ingestion of dietary proteins in diabetes type 1 exerts a delayed
      postprandial increase in blood glucose levels due to protein-induced stimulation
      of pancreatic glucagon secretion. Higher than minimal amounts of protein in the
      diet needed for nitrogen balance may play an important role for the increasing
      number of elderly obese subjects in our industrialized societies, since proteins
      exert beneficial effects in the conditions of overweight, metabolic syndrome,
      cardiovascular risk factors, bone health, and sarcopenia. Adverse effects of
      increased dietary proteins have been observed in subjects with renal impairment-
      this problem is frequently observed in the elderly, hypertensive, and diabetic
      population. Nevertheless, dietary proteins deserve more attention than they have
      received in the past.

PMID- 22139564
TI  - Protein intake and bone health.
AB  - Adequate nutrition plays an important role in the development and maintenance of
      bone structures resistant to usual mechanical stresses. In addition to calcium in
      the presence of an adequate supply of vitamin D, dietary proteins represent key
      nutrients for bone health and thereby function in the prevention of osteoporosis.
      Several studies point to a positive effect of high protein intake on bone mineral
      density or content. This fact is associated with a significant reduction in hip
      fracture incidence, as recorded in a large prospective study carried out in a
      homogeneous cohort of postmenopausal women. Low protein intake (< 0.8 g/kg body
      weight/day) is often observed in patients with hip fractures and an intervention
      study indicates that following orthopedic management, protein supplementation
      attenuates post-fracture bone loss, tends to increase muscle strength, and
      reduces medical complications and rehabilitation hospital stay. There is no
      evidence that high protein intake per se would be detrimental for bone mass and
      strength. Nevertheless, it appears reasonable to avoid very high protein diets
      (i. e. more than 2.0 g/kg body weight/day) when associated with low calcium
      intake (i. e. less than 600 mg/day). In the elderly, taking into account the
      attenuated anabolic response to dietary protein with ageing, there is concern
      that the current dietary protein recommended allowance (RDA), as set at 0.8 g/kg
      body weight/day, might be too low for the primary and secondary prevention of
      fragility fractures.

PMID- 22139565
TI  - Protein catabolism and requirements in severe illness.
AB  - Reduced total body protein mass is a marker of protein-energy malnutrition and
      has been associated with numerous complications. Severe illness is characterized
      by a loss of total body protein mass, mainly from the skeletal muscle. Studies on
      protein turnover describe an increased protein breakdown and, to a lesser extent,
      an increased whole-body protein synthesis, as well as an increased flux of amino
      acids from the periphery to the liver. Appropriate nutrition could limit protein
      catabolism. Nutritional support limits but does not stop the loss of total body
      protein mass occurring in acute severe illness. Its impact on protein kinetics is
      so far controversial, probably due to the various methodologies and
      characteristics of nutritional support used in the studies. Maintaining calorie
      balance alone the days after an insult does not clearly lead to an improved
      clinical outcome. In contrast, protein intakes between 1.2 and 1.5 g/kg body
      weight/day with neutral energy balance minimize total body protein mass loss.
      Glutamine and possibly leucine may improve clinical outcome, but it is unclear
      whether these benefits occur through an impact on total body protein mass and its
      turnover, or through other mechanisms. Present recommendations suggest providing
      20 - 25 kcal/kg/day over the first 72 - 96 hours and increasing energy intake to
      target thereafter. Simultaneously, protein intake should be between 1.2 and 1.5
      g/kg/day. Enteral immunonutrition enriched with arginine, nucleotides, and omega
      3 fatty acids is indicated in patients with trauma, acute respiratory distress
      syndrome (ARDS), and mild sepsis. Glutamine (0.2 - 0.4 g/kg/day of L-glutamine)
      should be added to enteral nutrition in burn and trauma patients (ESPEN
      guidelines 2006) and to parenteral nutrition, in the form of dipeptides, in
      intensive care unit (ICU) patients in general (ESPEN guidelines 2009).

PMID- 22139566
TI  - Dietary proteins and atherosclerosis.
AB  - More than one hundred years ago the "protein hypothesis" of the pathogenesis of
      atherosclerosis and its association with cardiovascular disease was put forward
      on the basis of animal experiments; however, it has so far never been verified in
      humans. This theory was soon replaced by the "lipid hypothesis", which was
      confirmed in humans as of 1994. Epidemiological ecological studies in the 1960 s
      showed significant associations between dietary animal protein and mortality from
      cardiovascular disease. However, animal protein intake was also significantly
      correlated with saturated fatty acid and cholesterol intake. In the last decades
      two prospective cohort studies demonstrated a decreased cardiovascular risk in
      women during high- versus low-protein intake when adjusting for other dietary
      factors (e. g., saturated fats) and other cardiovascular risk factors. A direct
      cholesterol lowering effect of proteins has not been shown. Despite earlier
      research indicating that soy protein has cardioprotective effects as compared to
      other proteins, these observations have not been confirmed by randomized placebo
      controlled trials. However, most experts recommend the consumption of foods rich
      in plant proteins as alternatives to meat and dairy products rich in saturated
      fat and containing cholesterol. There are no scientific arguments to increase the
      daily protein intake to more than 20 % of total energy intake as recommended by
      the guidelines, in order to improve cardiovascular health.

PMID- 22139567
TI  - Protein intake in renal and hepatic disease.
AB  - The kidney and the liver play a central role in protein metabolism. Synthesis of
      albumin and other proteins occurs mainly in the liver, whereas protein breakdown
      and excretion are handled through an intricate interaction between these two
      organ systems. Thus, disease states of either the liver and/or the kidney
      invariably result in clinically relevant disturbances of protein metabolism.
      Conversely, metabolic processes regulated by these two organs are directly
      affected by dietary protein intake. Of particular importance in this respect is
      the maintenance of acid/base homeostasis. Finally, both the amount and
      composition of ingested proteins have a direct impact on renal function,
      especially in a state of diseased kidneys. Consequently, dietary protein intake
      is of paramount importance in patients with chronic nephropathy and renal
      insufficiency. Limitation of ingested protein, particularly from animal sources,
      is crucial in order to slow the progression of chronic kidney disease and
      impaired renal function. In contrast, patients with chronic renal failure
      undergoing renal replacement therapy by hemodialysis or peritoneal dialysis, have
      an increased protein demand. The syndrome of "protein-energy malnutrition" is a
      relevant factor for morbidity and mortality in this population and requires early
      detection and vigorous treatment. Protein intake in patients with cirrhosis of
      the liver should not be diminished as has been earlier suggested but rather
      increased to 1.0 - 1.2 g/kg body weight/day, in order to prevent protein
      malnutrition. Moderate restriction depending on protein tolerance (0.5 - 1.2 g/kg
      body weight/day), with the possible addition of branched chain amino acids
      (BCAA), has been recommended only in patients with advanced hepatic
      encephalopathy. Proteins of plant origin are theoretically superior to animal
      proteins.

PMID- 22139568
TI  - Allergic reactions to food proteins.
AB  - Four to eight percent of the population are estimated to be food-allergic. Most
      food allergies in adolescents and adults are acquired on the basis of cross
      reaction to pollen allergens. Theses allergens are ubiquitous in the plant
      kingdom. Therefore pollen-allergic patients might acquire a multitude of
      different plant food allergies, and even react to novel foods to which they have
      never previously been exposed. A curative therapy for food allergy does not yet
      exist. Food-allergic patients have to rely on strict avoidance diets, The
      widespread use of industrially processed foods poses a general problem for food
      allergic patients. Although the most frequent allergens must be declared openly
      in the list of ingredients, involuntary contamination with allergy-provoking
      compounds can occur. The precautionary labelling "may contain" is sometimes
      applied even if the chance of contamination is very low; on the other hand, foods
      not declared to contain possible traces of allergenic components may actually
      contain relevant amounts of allergenic proteins. Switzerland is the only country
      in Europe with legal regulations on contamination by allergenic food; however,
      the allowance of 1 g/kg is too high to protect a relevant proportion of food
      allergic individuals.

PMID- 22139569
TI  - Bioactive proteins and peptides in foods.
AB  - Increasing amounts of data demonstrate a bioactive role of proteins and peptides
      above and beyond their nutritional impact. The focus of the investigations has
      mainly been on vitamin- and mineral-binding proteins, on antimicrobial,
      immunosuppressing/-modulatory proteins, and on proteins with enzyme inhibitory
      activity as well as on hormones and growth factors from different food proteins;
      most research has been performed on milk proteins. Because of their molecular
      size, intact absorption of proteins in the human gastrointestinal tract is
      limited. Therefore, most of the proteins with biological functions show
      physiological activity in the gastrointestinal tract by enhancing nutrient
      absorption, inhibiting enzymes, and modulating the immune system to defend
      against pathogens. Peptides are released during fermentation or digestion from
      food proteins by proteolytic enzymes; such peptides have been found mainly in
      milk. Some of these released peptides exert biological activities such as opiate
      like, antihypertensive, mineral-binding, antioxidative, antimicrobial, immuno-,
      and cytomodulating activity. Intact absorption of these smaller peptides is more
      likely than that of the larger proteins. Consequently, other organs than the
      gastrointestinal tract are possible targets for their biological functions.
      Bioactive proteins as well as bioactive peptides are part of a balanced diet. It
      is possible to accumulate bioactive peptides in food, for example by using
      specific microorganisms in fermented dairy products. Although bioactive peptides
      have been the subject of several studies in vitro and in vivo, their health
      potential is still under investigation. Up to now, the Commission of European
      Communities has not (yet) authorized any health claims for bioactive proteins and
      peptides from food.

PMID- 22139570
TI  - DNA methylation profiling in Barrett's esophagus and esophageal adenocarcinoma
      reveals unique methylation signatures and molecular subclasses.
AB  - Barrett's esophagus (BE) is a metaplastic process whereby the normal stratified,
      squamous esophageal epithelium is replaced by specialized intestinal epithelium.
      Barrett's is the only accepted precursor lesion for esophageal adenocarcinoma
      (EAC), a solid tumor that is rapidly increasing in incidence in western
      countries. BE evolves into EAC through intermediate steps that involve increasing
      degrees of dysplasia. Current histologic criteria are quite subjective and the
      clinical behavior of BE is highly variable and difficult to predict using these
      standards. It is widely believed that molecular alterations present in BE and EAC
      will provide more precise prognostic and predictive markers for these conditions
      than the current clinical and histologic features in use. In order to further
      define molecular alterations that can classify unique groups of BE and EAC, we
      utilized methylation microarrays to compare the global gene methylation status of
      a collection of normal squamous, BE, BE + high-grade dysplasia (HGD), and EAC
      cases. We found distinct global methylation signatures, as well as differential
      methylation of specific genes, that discriminated these histological groups. We
      also noted high and low methylation epigenotypes among the BE and EAC cases.
      Additional validation of those CpG sites that distinguished BE from BE + HGD and
      EAC may lead to the discovery of useful biomarkers with potential clinical
      applications in the diagnosis and prognosis of BE and EAC.

PMID- 22139571
TI  - Evidence of epigenetic regulation of the tumor suppressor gene cluster flanking
      RASSF1 in breast cancer cell lines.
AB  - Epigenetic mechanisms are frequently deregulated in cancer cells and can lead to
      the silencing of genes with tumor suppressor activities. The isoform A of the Ras
      association domain family member 1 (RASSF1A) gene is one of the most frequently
      silenced transcripts in human tumors, however, few studies have simultaneously
      investigated epigenetic abnormalities associated with the 3p21.3 tumor suppressor
      gene cluster flanking RASSF1 (i.e., SEMA3B, HYAL3, HYAL2, HYAL1, TUSC2, RASSF1,
      ZMYND10, NPRL2, TMEM115, and CACNA2D2). This study aimed to investigate the role
      of epigenetic changes to these genes in seventeen breast cancer cell lines and in
      three non-tumorigenic epithelial breast cell lines (184A1, 184B5, and MCF 10A)
      and to evaluate the effect on gene expression of treatment with the demethylating
      agent 5-Aza-2'-deoxycytidine and/or Trichostatin A (TSA), a histone deacetylase
      inhibitor. We report that, although the RASSF1A isoform was determined to be
      epigenetically silenced in 15 of the 17 breast cancer cell lines, all the cell
      lines expressed the RASSF1C isoform. Five breast cancer cell lines overexpressed
      RASSF1C, when compared to the normal epithelial cell line 184A1. Furthermore, the
      genes HYAL1 and CACNA2D2 were significantly overexpressed after the treatments.
      After the combinated treatment, RASSF1A re-expression was accompanied by an
      increase in expression levels of the flanking genes. The Spearman's correlation
      coefficient indicated a positive co-regulation of the following gene pairs:
      RASSF1 and TUSC2 (r=0.64, p=0.002), RASSF1 and ZMYND10 (r=0.58, p=0.07), RASSF1
      and NPRL2 (r=0.48, p=0.03), ZMYND10 and NPRL2 (r=0.71; p=0,0004), and NPRL2 and
      TMEM115 (r=0.66, p=0.001). Interestingly, the genes TUSC2, NPRL2 and TMEM115 were
      found to be unmethylated in each of the untreated cell lines. Chromatin
      immunoprecipitation using antibodies against the acetylated and trimethylated
      lysine 9 of histone H3 demonstrated low levels of histone methylation in these
      genes, which are located closest to RASSF1. These results provide evidence that
      epigenetic repression is involved in the down-regulation of multiple genes at
      3p21.3 in breast cancer cells.

PMID- 22139572
TI  - Increased promoter methylation in exfoliated breast epithelial cells in women
      with a previous breast biopsy.
AB  - Accurately identifying women at increased risk of developing breast cancer will
      provide greater opportunity for early detection and prevention. DNA promoter
      methylation is a promising biomarker for assessing breast cancer risk. Breast
      milk contains large numbers of exfoliated epithelial cells that are ideal for
      methylation analyses. Exfoliated epithelial cells were isolated from the milk
      obtained from each breast of 134 women with a history of a non-proliferative
      benign breast biopsy (Biopsy Group). Promoter methylation of three tumor
      suppressor genes, RASSF1, SFRP1 and GSTP1, was assessed by pyrosequencing of
      bisulfite-modified DNA. Methylation scores from the milk of the 134 women in the
      Biopsy Group were compared to scores from 102 women for whom a breast biopsy was
      not a recruitment requirement (Reference Group). Mean methylation scores for
      RASSF1 and GSTP1 were significantly higher in the Biopsy than in the Reference
      Group. For all three genes the percentage of outlier scores was greater in the
      Biopsy than in the Reference Group but reached statistical significance only for
      GSTP1. A comparison between the biopsied and non-biopsied breasts of the Biopsy
      Group revealed higher mean methylation and a greater number of outlier scores in
      the biopsied breast for both SFRP1 and RASSF1, but not for GSTP1. This is the
      first evidence of CpG island methylation in tumor suppressor genes of women who
      may be at increased risk of developing breast cancer based on having had a prior
      breast biopsy.

PMID- 22139573
TI  - History of Parvovirus B19 infection is associated with a DNA methylation
      signature in childhood acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) likely has a multistep etiology, with initial
      genetic aberrations occurring early in life. An abnormal immune response to
      common infections has emerged as a plausible candidate for triggering the
      proliferation of pre-leukemic clones and the fixation of secondary genetic
      mutations and epigenetic alterations. We investigated whether evidence of
      infection with a specific common myelotropic childhood virus, parvovirus B19
      (PVB19), relates to patterns of gene promoter DNA methylation in ALL patients. We
      serologically tested bone marrow samples at diagnosis of B-cell ALL for PVB19
      infection and DNA methylation using a high-throughput bead array and found that
      4.2% and 36.7% of samples were seroreactive to PVB19 IgM and IgG, respectively.
      Leukemia samples were grouped by DNA methylation pattern. Controlling for age and
      immunophenotype, unsupervised modeling confirmed that the DNA methylation pattern
      was associated with history of PVB19 (assessed by IgG, p = 0.02), but not recent
      infection (assessed by IgM). Replication assays on single genes were consistent
      with the association. The data indicate that a common viral illness may drive
      specific DNA methylation patterns in susceptible B-precursor cells, contributing
      to the leukemogenic potential of such cells. Infections may impact childhood
      leukemia by altering DNA methylation patterns and specific key genes in
      susceptible cells; these changes may be retained even after the clearance of
      infection.

PMID- 22139575
TI  - Increased DNA methylation of neuropsychiatric genes occurs in borderline
      personality disorder.
AB  - Borderline personality disorder (BPD) is a complex psychiatric disease of
      increasing importance. Epigenetic alterations are hallmarks for altered gene
      expression and could be involved in the etiology of BPD. In our study we analyzed
      DNA methylation patterns of 14 neuropsychiatric genes (COMT, DAT1, GABRA1, GNB3,
      GRIN2B, HTR1B, HTR2A, 5-HTT, MAOA, MAOB, NOS1, NR3C1, TPH1 and TH). DNA
      methylation was analyzed by bisulfite restriction analysis and pyrosequencing in
      whole blood samples of patients diagnosed with DSM-IV BPD and in controls.
      Aberrant methylation was not detectable using bisulfite restriction analysis, but
      a significantly increased methylation of HTR2A, NR3C1, MAOA, MAOB and soluble
      COMT (S-COMT) was revealed for BPD patients using pyrosequencing. For HTR2A the
      average methylation of four CpG sites was 0.8% higher in BPD patients compared to
      controls (p = 0.002). The average methylation of NR3C1 was 1.8% increased in BPD
      patients compared to controls (p = 0.0003) and was higher at 2 out of 8 CpGs (p
      <= 0.04). In females, an increased average methylation (1.5%) of MAOA was
      observed in BPD patients compared to controls (p = 0.046). A similar trend (1.4%
      higher methylation) was observed for MAOB in female BPD patients and increased
      methylation was significant for 1 out of 6 CpG sites. For S-COMT, a higher
      methylation of 2 out of 4 CpG sites was revealed in BPD patients (p <= 0.02). In
      summary, methylation signatures of several promoter regions were established and
      a significant increased average methylation (1.7%) occurred in blood samples of
      BPD patients (p < 0.0001). Our data suggest that aberrant epigenetic regulation
      of neuropsychiatric genes may contribute to the pathogenesis of BPD.

PMID- 22139574
TI  - Identification of a core member of the SWI/SNF complex, BAF155/SMARCC1, as a
      human tumor suppressor gene.
AB  - Recent studies have established that two core members of the SWI/SNF chromatin
      remodeling complex, BRG1 and SNF5/INI1, possess tumor-suppressor activity in
      human and mouse cancers. While the third core member, BAF155, has been implicated
      by several studies as having a potential role in tumor development, direct
      evidence for its tumor suppressor activity has remained lacking. Therefore, we
      screened for BAF155 deficiency in a large number of human tumor cell lines. We
      identified 2 cell lines, the SNUC2B colon carcinoma and the SKOV3 ovarian
      carcinoma, displaying a complete loss of protein expression while maintaining
      normal levels of mRNA expression. The SKOV3 cell line possesses a heterozygous
      4bp deletion that results in an 855AA truncated protein, while the cause of the
      loss of BAF155 expression in the SNUC2B cell line appears due to a post
      transcriptional error. However, the lack of detectable BAF155 expression did not
      affect sensitivity to RB-mediated cell cycle arrest. Re-expression of full length
      but not a truncated form of BAF155 in the two cancer cell lines leads to reduced
      colony forming ability characterized by replicative senescence but not apoptosis.
      Collectively, these data suggest that loss of BAF155 expression represents
      another mechanism for inactivation of SWI/SNF complex activity in the development
      in human cancer. Our results further indicate that the c-terminus proline
      glutamine rich domain plays a critical role in the tumor suppressor activity of
      this protein.

PMID- 22139576
TI  - Protective effects of valproic acid against airway hyperresponsiveness and airway
      remodeling in a mouse model of allergic airways disease.
AB  - Airway remodeling and airway hyperresponsiveness are major aspects of asthma
      pathology that are not targeted optimally by existing anti-inflammatory drugs.
      Histone deacetylase inhibitors have a wide range of effects that may potentially
      abrogate aspects of remodeling. One such histone deacetylase inhibitor is
      valproic acid (2-propylvaleric acid). Valproic acid is used clinically as an anti
      epileptic drug and is a potent inhibitor of class I histone deacetylases but also
      inhibits class II histone deacetylases. We used valproic acid as a molecular
      model of histone deacetylase inhibition in vivo in chronic allergic airways
      disease mice with airway remodeling and airway hyperresponsiveness. Wild-type
      Balb/c mice with allergic airways disease were treated with valproic acid or
      vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid
      cell counts and examination of lung tissue sections. Remodeling was assessed by
      morphometric analysis of histochemically stained slides and lung function was
      assessed by invasive plethysmography measurement of airway resistance. Valproic
      acid treatment did not affect inflammation parameters; however, valproic acid
      treatment resulted in reduced epithelial thickness as compared to vehicle treated
      mice (p < 0.01), reduced subepithelial collagen deposition (p < 0.05) and
      attenuated airway hyperresponsiveness (p < 0.05 and p < 0.01 for the two highest
      doses of methacholine, respectively). These findings show that treatment with
      valproic acid can reduce structural airway remodeling changes and
      hyperresponsiveness, providing further evidence for the potential use of histone
      deacetylase inhibitors for the treatment of asthma.

PMID- 22139578
TI  - The inactivation of the pi gene in chicken erythroblasts of adult lineage is not
      mediated by packaging of the embryonic part of the alpha-globin gene domain into
      a repressive heterochromatin-like structure.
AB  - The developmental switch of globin gene expression is a characteristic feature of
      vertebrate organisms. The switch of beta-globin expression is believed to depend
      on reconfiguration of the active chromatin hub, which contains transcribed genes
      and regulatory elements. Mechanisms controlling the switch of alpha-globin gene
      expression are less clear. Here, we studied the mode of chromatin packaging of
      the chicken alpha-globin gene domain in red blood cells (RBCs) of primitive and
      definite lineages and the spatial configuration of this domain in RBCs of
      primitive lineage. It has been demonstrated that RBCs of primitive lineage
      already contain the adult-type active chromatin hub but the embryonal alpha-type
      globin pi gene is not recruited to this hub. Distribution of active and
      repressive histone modifications over the alpha-globin gene domain in RBCs of
      definite and primitive lineages does not corroborate the hypothesis that
      inactivation of the pi gene in RBCs of adult lineage is mediated via formation of
      a local repressed chromatin domain. This conclusion is supported by the
      demonstration that in chicken erythroblasts of adult lineage, the embryonal and
      adult segments of the alpha-globin gene domain show similar elevated
      sensitivities to DNase I.

PMID- 22139577
TI  - Germ cell-specific DNA methylation and genome diploidization in primitive
      vertebrates.
AB  - Genomic imprinting in mammals causes certain genes to be expressed according to
      their parental origin and thereby prevents parthenogenesis. However, the
      evolutionary origin and significance of genomic imprinting remains unclear. Here,
      we study the methylation status of ntl, a developmentally decisive gene, in egg,
      sperm and early embryos at various developmental stages in bisexual diploid fish
      and unisexual polyploid fish. Bisulfite sequencing analysis revealed that
      maternal-specific methylation occurs at ntl promoter during gametogenesis in
      bisexual diploid fish, where the epigenetic asymmetry of the parental alleles is
      maintained during cleavage, but methylation does not occur at ntl promoter in
      unisexual polyploid fish. Knocking down Kaiso, a methyl-CpG dependent
      transcription repressor, greatly increased the expression level of the methylated
      maternal allele during early embryogenesis and rescued the failure of anterior
      notochord formation in the gynogenetic haploid of bisexual fish. This indicated
      that the methylated maternal ntl allele is silent during early embryogenesis and
      this early silencing is dependent on the methylated-CpG binding protein Kaiso.
      Using single sequence polymorphisms in distinguishing paternally and maternally
      derived transcripts in the diploid fish, we demonstrated that the unmethylated
      paternal allele begins transcription at the 2-cell stage and maintains
      transcriptional activity during cleavage. These results suggest that genomic
      imprinting originates from primitive vertebrates in association with genome
      diploidization and bisexual reproduction during vertebrate genome evolution and
      has a clear effect in preventing parthenogenesis.

PMID- 22139579
TI  - Dramatic replacement of histone variants during genome remodeling in nuclear
      transferred embryos.
AB  - The genome of differentiated somatic nuclei is remodeled to a totipotent state
      when they are transplanted into enucleated oocytes. To clarify the mechanism of
      this genome remodeling, we analyzed changes in the composition of core histone
      variants in nuclear-transferred embryos, since recent evidence has revealed that
      chromatin structure can be remodeled as a result of variant histone replacement.
      We found that the donor cell-derived histone H3 variants H3.1, H3.2, and H3.3, as
      well as H2A and H2A.Z, were rapidly eliminated from the chromatin of nuclei
      transplanted into enucleated oocytes. Accompanying this removal, oocyte-stored
      histone H3 variants and H2A.X were incorporated into the transplanted nuclei,
      while the incorporation of H2A and H2A.Z was minimal or not detected. The
      incorporation of these variant histones was DNA replication-independent. These
      results suggest that most core histone H2A and H3 components are dynamically
      exchanged between donor nuclei and recipient cytoplasm, which further suggests
      that replacement of donor cell histones with oocyte-stored histones may play a
      key role in genome remodeling in nuclear-transferred embryos. In addition, the
      incorporation patterns of all of the histone variants in the nuclear-transferred
      embryos were virtually the same as in the fertilized embryos. Only the
      incorporation pattern of H3.1 differed; it was incorporated into the transplanted
      donor nuclei, but not in the pronuclei of fertilized embryos. This result
      suggests that the incorporation of H3.1 has a detrimental effect on the process
      of genome remodeling and contributes to the low success rate of somatic nuclear
      cloning.

PMID- 22139581
TI  - EpiRegNet: constructing epigenetic regulatory network from high throughput gene
      expression data for humans.
AB  - The advances of high throughput profiling methods, such as microarray gene
      profiling and RNA-seq, have enabled researchers to identify thousands of
      differentially expressed genes under a certain perturbation. Much work has been
      done to understand the genetic factors that contribute to the expression changes
      by searching the over-represented regulatory motifs in the promoter regions of
      these genes. However, the changes could also be caused by epigenetic regulation,
      especially histone modifications, and no web server has been constructed to study
      the epigenetic factors responsible for gene expression changes. Here, we pre-sent
      a web tool for this purpose. Provided with different categories of genes (e.g.,
      up-regulated, down-regulated or unchanged genes), the server will find epigenetic
      factors responsible for the difference among the categories and construct an
      epigenetic regulatory network. Furthermore, it will perform co-localization
      analyses between these epigenetic factors and transcription factors, which were
      collected from large scale experimental ChIP-seq or computational predicted data.
      In addition, for users who want to analyze dynamic change of a histone
      modification mark under different cell conditions, the server will find direct
      and indirect target genes of this mark by integrative analysis of experimental
      data and computational prediction, and present a regulatory network around this
      mark. Both networks can be visualized by a user friendly interface and the data
      are downloadable in batch. The server currently supports 12 cell types in human,
      including ESC and CD4+ T cells, and will expand as more public data are
      available. It also allows user to create a self-defined cell type, upload and
      analyze multiple ChIP-seq data. It is freely available to academic users at
      http://jjwanglab.org/EpiRegNet.

PMID- 22139580
TI  - Neonatal DNA methylation patterns associate with gestational age.
AB  - Risk for adverse neonatal outcome increases with declining gestational age (GA),
      and changes in DNA methylation may contribute to the relationship between GA and
      adverse health outcomes in offspring. To test this hypothesis, we evaluated the
      association between GA and more than 27,000 CpG sites in neonatal DNA extracted
      from umbilical cord blood from two prospectively-characterized cohorts: (1) a
      discovery cohort consisting of 259 neonates from women with a history of
      neuropsychiatric disorders and (2) a replication cohort consisting of 194
      neonates of uncomplicated mothers. GA was determined by obstetrician report and
      maternal last menstrual period. The associations between proportion of DNA
      methylated and GA were evaluated by fitting a separate linear mixed effects model
      for each CpG site, adjusting for relevant covariates including neonatal sex,
      race, parity, birth weight percentile and chip effects. CpG sites in 39 genes
      were associated with GA (false discovery rate < 0.05) in the discovery cohort.
      The same CpG sites in 25 of these genes replicated in the replication cohort,
      with each association replicating in the same direction. Notably, these CpG sites
      were located in genes previously implicated in labor and delivery (e.g., AVP,
      OXT, CRHBP and ESR1) or that may influence the risk for adverse health outcomes
      later in life (e.g., DUOX2, TMEM176A and CASP8). All associations were
      independent of method of delivery or induction of labor. These results suggest
      neonatal DNA methylation varies with GA even in term deliveries. The potential
      contribution of these changes to clinically significant postnatal outcomes
      warrants further investigation.

PMID- 22139582
TI  - A case of factor V inhibitor with complete correction of the PT and aPTT upon
      mixing.
AB  - We read with interest Gartrell's recent report of a woman who developed a factor
      V inhibitor. Gartrell noted in his report that the inhibitor appeared to exhibit
      time dependence, as the mixing study showed slightly more prolongation of both
      the PT and the aPTT after 1 hr than immediately following mixing. We believe
      Gartrell's article may shed light on a recent intriguing case of a patient with
      factor V inhibitor at our institution.

PMID- 22139583
TI  - Growing trend of CE at the omics level: the frontier of systems biology--an
      update.
AB  - Omics is the study of proteins, peptides, genes, and metabolites in living
      organisms. Systems biology aims to understand the system through the study of the
      relationship between elements such as genes and proteins in biological system.
      Recently, systems biology emerged as the result of the advanced development of
      high-throughput analysis technologies such as DNA sequencers, DNA arrays, and
      mass spectrometry for omics studies. Among a number of analytical tools and
      technologies, CE and CE coupled to MS are promising and relatively rapidly
      developing tools with the potential to provide qualitative and quantitative
      analyses of biological molecules. With an emphasis on CE for systems biology,
      this review summarizes the method developments and applications of CE for the
      genomic, transcriptomic, proteomic, and metabolomic studies focusing on the drug
      discovery and disease diagnosis and therapies since 2009.

PMID- 22139584
TI  - Thy28 partially prevents apoptosis induction following engagement of membrane
      immunoglobulin in WEHI-231 B lymphoma cells.
AB  - Thy28 protein is conserved among plants, bacteria, and mammalian cells. Nuclear
      Thy28 protein is substantially expressed in testis, liver, and immune cells such
      as lymphocytes. Lymphocyte apoptosis plays a crucial role in homeostasis and
      formation of a diverse lymphocyte repertoire. In this study, we examined whether
      Thy28 affects induction of apoptosis in WEHI-231 B lymphoma cells following
      engagement of membrane immunoglobulin (mIg). Once they were established, the
      Thy28-overexpressing WEHI-231 cells showed similar expression levels of IgM and
      class I major histocompatibility complex (MHC) molecule compared with controls.
      The Thy28-overexpressing cells were considerably resistant to loss of
      mitochondrial membrane potential (DeltaPsim), caspase-3 activation, and increase
      in annexin-positive cells upon mIg engagement. These changes were concomitant
      with an increase in G1 phase associated with upregulation of p27(Kip1). The anti
      IgM-induced sustained activation of c-Jun N-terminal kinase (JNK), which was
      associated with late-phase hydrogen peroxide (H(2)O(2)) production, was partially
      reduced in the Thy28-expressing cells relative to controls. Taken together, the
      data suggest that in WEHI-231 B lymphoma cells, Thy28 regulates mIg-mediated
      apoptotic events through the JNK-H(2)O(2) activation pathway, concomitant with an
      accumulation of cells in G1 phase associated with upregulation of p27(Kip1) in
      WEHI-231 B lymphoma cells.

PMID- 22139585
TI  - Proteomic analysis of tumor tissue in CT-26 implanted BALB/C mouse after
      treatment with ascorbic acid.
AB  - Tumor establishment and penetration consists of a series of complex processes
      involving multiple changes in gene expression and protein modification. Proteome
      changes of tumor tissue were investigated after intraperitoneal administration of
      a high concentration of ascorbic acid in BALB/C mice implanted with CT-26 cancer
      cells using two-dimensional gel electrophoresis and mass spectrometry. Eighteen
      protein spots were identified whose expression was different between control and
      ascorbic acid treatment groups. In particular, eukaryotic translation initiation
      factor 3 subunit 1, nucleophosmin, latexin, actin-related protein 2/3 complex
      subunit 5, M2-type pyruvate kinase, vimentin, tumor protein translationally
      controlled 1, RAS oncogene family Ran, plastin 3 precursor, ATPase, Rho GDT
      dissociation inhibitor beta, and proteasome activator subunit 2 expression were
      quantitatively up-regulated. The increase in the level of these proteins was
      accompanied by an increase in mRNA level. The cytoskeleton protein actin,
      vimentin, and tumor protein translationally-controlled 1 showed quantitative
      expression profile differences. A change in actin cytoskeleton distribution,
      functionally relevant to the proteome result, was observed after treatment with
      ascorbic acid. These results suggest a previously undefined role of ascorbic acid
      in the regulation of cytoskeleton remodeling in tumor tissues.

PMID- 22139586
TI  - The cytotoxic effect of diphtheria toxin on the actin cytoskeleton.
AB  - Diphtheria toxin (DT) and its N-terminal fragment A (FA) catalyse the transfer of
      the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD) into a covalent
      linkage with eukaryotic elongation factor 2 (eEF2). DT-induced cytotoxicity is
      versatile, and it includes DNA cleavage and the depolymerisation of actin
      filaments. The inhibition of the ADP-ribosyltransferase (ADPrT) activity of FA
      did not affect the deoxyribonuclease activity of FA or its interaction with
      actin. The toxin entry rate into cells (HUVEC) was determined by measuring the
      ADP-ribosyltransferase activity. DT uptake was nearly 80% after 30 min. The
      efficiency was determined as K(m) = 2.2 nM; V(max) = 0.25 pmol.min(-1). The
      nuclease activity was tested with hyperchromicity experiments, and it was
      concluded that G-actin has an inhibitory effect on DT nuclease activity. In the
      presence of DT and mutant of diphtheria toxin (CRM197), F-actin depolymerisation
      was determined with gel filtration, WB and fluorescence techniques. In the
      presence of DT and CRM197, 60-65% F-actin depolymerisation was observed. An in
      vitro FA-actin interaction and F-actin depolymerisation were reported in our
      previous paper. The present study thus confirms the depolymerisation of actin
      cytoskeleton in vivo.

PMID- 22139587
TI  - Adverse events from calcium supplementation: relationship to errors in myocardial
      infarction self-reporting in randomized controlled trials of calcium
      supplementation.
AB  - The clinical effects of calcium supplements on adverse events reporting have not
      been well described. This study reviews randomized controlled trial (RCT)
      evidence of adverse events to clarify the epidemiology of these events. The
      hypothesis that patient self-report of myocardial infarction (MI) is increased in
      individuals receiving calcium supplementation is because of an increase in non-MI
      events incorrectly perceived by the patient as being because of MI, is examined.
      In seven RCTs summary self-reported gastrointestinal (GI) adverse event rates
      were more common in participants receiving calcium. These were described as
      constipation, excessive abdominal cramping, bloating, upper GI events, GI
      disease, GI symptoms, and severe diarrhoea or abdominal pain (calcium 14.1%,
      placebo 10.0%), relative risk (RR) 1.43 95% confidence interval (CI) 1.28 to
      1.59, p < 0.001. Adjudicated functional GI hospitalizations in one study were
      calcium 6.8%, placebo 3.6% (RR 1.92, 95% CI 1.21-3.05, p = 0.006). Direct
      comparison of self-reported and adjudicated MI events in the two trials of
      dietary calcium supplementation showed self-reported MI rates of 3.6% in the
      calcium group and 2.1% in the placebo group. After adjudication the MI rates were
      2.4% in the calcium group and 1.6% in the placebo group (RR 1.45, 95% CI 0.88
      2.45, p = 0.145). These data support the hypothesis that calcium tablets increase
      the incidence of adverse GI events, which may account for an increase in self
      reported MI in calcium treated patients but not controls.

PMID- 22139588
TI  - Analysis of 43 cases of Langerhans cell histiocytosis (LCH)-induced central
      diabetes insipidus registered in the JLSG-96 and JLSG-02 studies in Japan.
AB  - To determine the ability of recent systemic chemotherapy protocols to reduce the
      incidence of central diabetes insipidus (CDI) in Langerhans cell histiocytosis
      (LCH), 43 CDI cases that belonged to a cohort of 348 pediatric patients with
      multi-focal LCH who were treated with the JLSG-96/-02 protocols were analyzed.
      The overall incidence of CDI was 12.4%, but in 24 cases CDI was already present
      at the time LCH was diagnosed. Thus, CDI developed during or after systemic
      chemotherapy over a follow-up period of 5.0 (0.2-14.7) years in only 19 patients
      (5.9%), with 7.4% at 5-year cumulative risk by Kaplan-Meier analysis. In two
      cases, complete resolution of CDI was noted. Anterior pituitary hormone
      deficiency was detected in 13 cases, while CDI-associated neurodegenerative
      disease was observed in six cases. The JLSG-96/-02 protocol appears to
      effectively reduce the occurrence of CDI. However, novel therapeutic measures are
      required to reverse pre-existing CDI and to prevent CDI-associated neurological
      complications.

PMID- 22139589
TI  - HIV/AIDS in Women and Racial/Ethnic Minorities in the U.S.
AB  - The clinical issues affecting women with HIV/AIDS differ little from those
      affecting men. However, current research shows that treatment and outcome
      disparities affect many women with HIV, hypothesized to result from a complex
      interplay of socioeconomic and gender role influences. These disparities are also
      a reflection of racial/ethnic differences in treatment and outcome, since 80% of
      women with HIV/AIDS are black or Hispanic. Women have unique needs for HIV
      prevention - both prevention of sexual transmission to or from sexual partners
      and prevention of perinatal transmission. Racial/ethnic minorities continue to be
      disproportionately affected by the HIV/AIDS epidemic in the U.S. Minorities are
      less likely to be in care and on HAART than others with HIV/AIDS. These
      disparities result in poorer outcomes for minorities, especially blacks, with
      HIV/AIDS. New strategies for optimizing engagement and retention in care, and for
      prevention hold great promise for women and minorities with HIV in the U.S.

PMID- 22139590
TI  - Safety assessment and pharmacokinetics of intrathecal methylprednisolone acetate
      in dogs.
AB  - BACKGROUND: Intrathecal methylprednisolone acetate (MPA) has been used in
      patients with chronic pain syndromes. Its safety has been debated after reports
      of adverse events. No systematic preclinical evaluation of MPA has been reported.
      In the current study, the acute and long-term effects of intrathecal MPA on dog
      spinal tissue was studied with the injectate reformulated to include minimal
      adjuvants. METHODS: Seventeen dogs were implanted with intrathecal catheters and
      randomized to three groups: vehicle (lidocaine; 4 dogs), MPA 20 mg/ml (human
      dose; 7 dogs), and MPA 80 mg/ml (maximum deliverable dose; 6 dogs). In parallel
      with the human protocols, dogs received four injections at 7-day intervals.
      Clinical observations and plasma methylprednisolone measurements were done before
      and at intervals after intrathecal delivery. One week (acute) or 6 weeks (long
      term) after the last injection, animals were sacrificed and spinal tissues
      harvested for histopathology. RESULTS: Other than a brief motor block, no adverse
      clinical event occurred in any animal. Group A (vehicle) showed minimal
      histologic changes (median histology-score; acute: 1.3, long-term: 1.0). Group B
      (MPA 20 mg/ml) had a diffuse inflammatory reaction (acute: 2.0, long-term: 3.0),
      group C (MPA 80 mg/ml) a severe inflammatory response, with large inflammatory
      masses (acute: 4.0, long-term: 7.0) The severity of the inflammatory reaction
      increased significantly with increasing dose at long-term sacrifice (acute P =
      0.167, long-term P = 0.014). No neuronal injury, demyelination, or gliosis was
      seen in any animal. CONCLUSION: These results, showing dose-dependent intrathecal
      inflammatory reactions at MPA doses and injectate concentrations comparable to
      those used in humans, indicate that the continued use of this modality in humans
      is not recommended.

PMID- 22139591
TI  - Lamotrigine XR conversion to monotherapy: first study using a historical control
      group.
AB  - The efficacy and safety of lamotrigine extended-release tablets (LTG XR) as
      monotherapy for partial seizures were evaluated using the conversion-to
      monotherapy design, and historical data as the control. This methodology was
      recently approved by the United States Food and Drug Administration, and this
      study is the first historical control design in epilepsy to complete enrollment.
      Patients >=13 years old with uncontrolled partial epilepsy receiving monotherapy
      with valproate or a noninducing antiepileptic drug were converted to once-daily
      LTG XR (250 mg or 300 mg) as monotherapy and were followed up for 12 additional
      weeks. Efficacy was measured by the proportion of patients meeting predefined
      escape criteria for seizure worsening compared with aggregated pseudoplacebo
      control data from 8 previously conducted conversion-to-monotherapy trials.
      Nonoverlap of the 95% confidence limit for LTG XR and the 95% prediction interval
      of the historical control denotes efficacy. Of 226 randomized patients, 174 (93
      in 300 mg/day group and 81 in 250 mg/day group) started withdrawal of the
      background AED and were evaluated for escape. In the historical control analysis
      population, the lower 95% prediction interval of the historical control (65.3%)
      was not overlapped by the upper 95% confidence limit of either LTG XR (300
      mg/day; 37.2%) or LTG XR (250 mg/day; 43.4%). Adverse events were reported in 53%
      and 61% of patients receiving LTG XR (300 mg/day and 250 mg/day, respectively).
      LTG XR (250 mg or 300 mg once daily) is effective for conversion-to-monotherapy
      treatment of partial seizures in patients >=13 years old.

PMID- 22139595
TI  - CE and CEC analysis of phytochemicals in herbal medicines.
AB  - CE and CEC, due to their versatility and high efficiency, have attracted great
      interest in the analysis of phytochemicals in herbs and their preparations.
      Previously, we reviewed the analysis of phytochemical bioactive compounds by CE
      in 2006 (Electrophoresis 2006, 27, 4808-4819) or CEC in 2010 (Electrophoresis
      2010, 31, 260-277). This review followed the previous studies and covered the
      literature published since 2006 for CE and 2009 for CEC (excluding those
      mentioned in the two previous reviews), which emphasized the development of CE
      and CEC techniques in phytochemical analysis. In addition, sample preparation and
      detection were also discussed.

PMID- 22139593
TI  - A case of mistaken identity: HSPs are no DAMPs but DAMPERs.
AB  - Until recently, the immune system was seen solely as a defense system with its
      primary task being the elimination of unwanted microbial invaders. Currently,
      however, the functional significance of the immune system has obtained a much
      wider perspective, to include among others the maintenance and restoration of
      homeostasis following tissue damage. In this latter aspect, there is a growing
      interest in the identification of molecules involved, such as the so-called
      danger or damage-associated molecular patterns (DAMPs), also called alarmins.
      Since heat shock proteins are archetypical molecules produced under stressful
      conditions, such as tissue damage or inflammation, they are frequently mentioned
      as prime examples of DAMPs (Bianchi, J Leukoc Biol 81:1-5, 2007; Kono and Rock,
      Nat Rev Immunol 8:279-289, 2008; Martin-Murphy et al., Toxicol Lett 192:387-394,
      2010). See for instance also a recent review (Chen and Nunez, Science 298:1395
      1401, 2010). Contrary to this description, we recently presented some of the
      arguments against a role of heat shock protein as DAMPs (Broere et al., Nat Rev
      Immunol 11:565-c1, 2011). With this perspective and reflection article, we hope
      to elaborate on this debate and provide additional thoughts to further ignite
      this discussion on this critical and evolving issue.

PMID- 22139592
TI  - Therapeutic strategies in acute intracerebral hemorrhage.
AB  - Intracerebral hemorrhage is a devastating disease, and no specific therapy has
      been proven to reduce mortality in a randomized controlled trial. However,
      management in a neuroscience intensive care unit does appear to improve outcomes,
      suggesting that many available therapies do in fact provide benefit. In the acute
      phase of intracerebral hemorrhage care, strategies aimed at minimizing ongoing
      bleeding include reversal of anticoagulation and modest blood pressure reduction.
      In addition, the monitoring and regulation of glucose levels, temperature, and,
      in selected cases, intracranial pressure are recommended by many groups. Selected
      patients may benefit from hematoma evacuation or external ventricular drainage.
      Ongoing clinical trials are examining aggressive blood pressure management,
      hemostatic therapy, platelet transfusion, stereotactic hematoma evacuation, and
      intraventricular thrombolysis. Finally, preventing recurrence of intracerebral
      hemorrhage is of pivotal importance, and tight blood pressure management is
      paramount.

PMID- 22139596
TI  - Intravenous or oral iron?

PMID- 22139594
TI  - The role of innate immunity in the host defense against intestinal bacterial
      pathogens.
AB  - Eradication of infectious disease is our global health challenge. After
      encountering intestinal infection with a bacterial pathogen, the host defense
      program is initiated by local antigen-presenting cells (APCs) that eliminate
      invading pathogens by phagocytosis and establish localized inflammation by
      secreting cytokines and chemokines. These pathogen-experienced APCs migrate to
      the mesenteric lymph nodes, where host immune responses are precisely
      orchestrated. Initiation and regulation of this defense program appear to be
      largely dependent on innate immunity which is antigen non-specific and provides a
      rapid defense against broader targets. On the other hand, many bacterial
      enteropathogens have evoked abilities to modify the host defense program to their
      advantage. Therefore, better understanding of the host-pathogen interactions is
      essential to establish effective eradication strategies for enteric infectious
      diseases. In this review, we will discuss the current understanding of innate
      immune regulation of the host defense mechanisms against intestinal infection by
      bacterial pathogens.

PMID- 22139597
TI  - Surgical response to the 2008 Mumbai terror attack.
AB  - BACKGROUND: Mumbai, the financial capital of India, was attacked by terrorists at
      various famous, densely populated places on 26 November 2008. The attack lasted
      for 60 h, resulting in multiple civilian casualties from bullet and blast
      injuries. The aim was to review the disaster management plan and analyse the
      injury patterns and surgical response. METHODS: The disaster management plan was
      activated in the Sir Jamshetjee Jejeebhoy Group of Hospitals as soon as the
      earliest casualties were reported. The casualty receiving area was converted into
      a triage zone; patients were accordingly sent to different stations for further
      management. There was rotation of the duties of the medical personnel every 8 h
      for increased efficiency. RESULTS: A total of 271 casualties were encountered, of
      which 108 were dead at admission. Some 163 patients were triaged, 23 of whom
      received primary care as outpatients. The remaining 140 patients needed admission
      to hospital; 194 operations were performed in 127 patients. There were six
      postoperative deaths. CONCLUSION: This was a unique terrorist attack targeted on
      civilians and continuing for more than 2 days. The casualties consisted of
      military injuries due to combined firearm and blast trauma. Primary triage, or
      onsite triage once the site is safe, optimizes management.

PMID- 22139599
TI  - Copper and liver disease.

PMID- 22139601
TI  - The acute and long-term effectiveness of amisulpride in patients with
      schizophrenia: results of a 12-month open-label prospective follow-up study.
AB  - OBJECTIVE: To compare the effectiveness of amisulpride in acute (up to 8 weeks)
      and maintenance (week 8 to 12 months) phases of a 12-month course of treatment in
      a heterogeneous group of patients with schizophrenia. METHODS: We conducted a 12
      month, open-label clinical trial with flexible doses of amisulpride among 129
      Korean patients with schizophrenia. The Positive and Negative Symptom Scale
      (PANSS) and several other scales measuring efficacy and tolerability were
      analyzed during the acute and maintenance phases. RESULTS: The completion rates
      were 78.3% by week 8 and 55.8% by month 12. Total PANSS scores and scores on the
      negative-symptom and general-symptom subscales improved significantly during both
      acute and maintenance periods, but scores on the positive-symptom subscale
      improved only during the acute phase. Improvement during both treatment phases
      was significant in all other scales except for the Drug Attitude Inventory. The
      negative-symptom and mixed-symptom groups showed significant improvement in the
      PANSS negative subscale, the Clinical Global Impression scale, and the Global
      Assessment of Functioning during the maintenance period. Hyperprolactinemia and
      related events were commonly reported. CONCLUSIONS: This study demonstrated the
      significant effectiveness and a good safety profile of amisulpride for treating
      acute and 12-month phases of schizophrenia under natural conditions.

PMID- 22139604
TI  - A truncation mutation of the neurovirulence ICP22 protein produced by a
      recombinant HSV-1 generated by bacterial artificial chromosome technology targets
      infected cell nuclei.
AB  - The major regulatory protein ICP22 is unique among the immediate early proteins
      of herpes simplex virus. Viruses deleted for ICP22 replicate well in actively
      dividing cells, but not in quiescent cells or certain rodent lines. Accordingly,
      ICP22 represents an understudied herpes simplex virus (HSV) neurovirulence marker
      which is absolutely essential for viral neurogrowth. We utilized the bacterial
      artificial chromosome methodology to create a novel ICP22 truncation mutant,
      termed HSV-1(BACX). The integrity of HSV-1(BACX) was confirmed by detailed
      polymerase chain reaction analyses and immunoblotting using anti-ICP22 antibody.
      HSV-1(BACX) showed a reduced replication capacity in rabbit skin cells,
      consistent with previous studies using ICP22-null viruses. Importantly, HSV
      1(BACX) localized to nuclei of infected primate Vero cells in a manner similar to
      wild-type ICP22. Thus, HSV-1(BACX) will serve as a useful tool to decipher the
      unusual biological properties and functions of the ICP22 protein.

PMID- 22139605
TI  - Influence of sigma-1 receptor modulators on ethanol-induced conditioned place
      preference in the extinction-reinstatement model.
AB  - Sigma-1 receptor agonists are reported to augment and antagonists block the
      rewarding effects of drugs of abuse. However, their effect on reinstatement of
      ethanol-induced conditioned place preference (CPP) has not yet been explored.
      Therefore, we investigated the ability of 2-(4-morpholino)ethyl-1
      phenylcyclohexane-1-carboxylate (PRE-084), a sigma-1 receptor agonist, and N-[2
      (3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine dihydrobromide
      (BD-1047), a sigma-1 receptor antagonist, on the acquisition, expression, and
      reinstatement of ethanol-induced CPP using adult male Swiss mice. BD-1047 (0.1-10
      MUg/mouse, intracerebroventricularly) dose-dependently blocked the development,
      expression, and reinstatement of ethanol-induced CPP, and PRE-084 (0.01-10
      MUg/mouse, intracerebroventricularly) dose-dependently reinstated the
      extinguished response. These effects of PRE-084 and BD-1047 alone or in
      combination with ethanol did not influence the motor activity. Therefore, it is
      concluded that sigma-1 receptor ligands can modulate the acquisition, expression,
      and reinstatement of conditioned reinforcing effects of ethanol with no
      reinforcing or aversive influence of their own. The results add to the growing
      literature on sigma-1 receptor modulation in the pharmacotherapy of ethanol
      addiction.

PMID- 22139606
TI  - Intrahippocampal injection of brain-derived neurotrophic factor increases anxiety
      related, but not panic-related defensive responses:  involvement of serotonin.
AB  - Changes in brain-derived neurotrophic factor (BDNF)-mediated signaling in the
      hippocampus have been implicated in the etiology of depression and in the mode of
      action of antidepressant drugs. There is also evidence from animal studies to
      suggest that BDNF-induced changes in the hippocampus may play a role in another
      stress-related pathology: anxiety. However, it is still unknown whether this
      neurotrophin plays a differential role in defensive responses associated with
      distinguished subtypes of anxiety disorders found in the clinic, such as
      generalized anxiety and panic disorder. In the present study, we investigated the
      effect of an acute BDNF injection into the rat dorsal hippocampus (DH) on
      inhibitory avoidance acquisition and escape expression measured in the elevated T
      maze (ETM). We also assessed whether serotonergic neurotransmission may account
      for such effects. Intra-DH BDNF injection (200 pg) facilitated inhibitory
      avoidance in ETM. BDNF was equally anxiogenic in the light/dark transition test.
      Preadministration of the 5-HT1A receptor antagonist WAY-100635 fully counteracted
      the anxiogenic effect of BDNF in both tests. Intra-DH midazolam administration
      (10 nmol) impaired avoidance acquisition in ETM, suggesting an anxiolytic effect.
      Therefore, in the DH, facilitation of BDNF signaling seems to enhance 5-HT1A
      receptor-mediated neurotransmission to exert an anxiogenic effect associated with
      generalized anxiety.

PMID- 22139602
TI  - Regulation of the latency-reactivation cycle by products encoded by the bovine
      herpesvirus 1 (BHV-1) latency-related gene.
AB  - Like other alpha-herpesvirinae subfamily members, the primary site for bovine
      herpesvirus 1 (BHV-1) latency is ganglionic sensory neurons. Periodically BHV-1
      reactivates from latency, virus is shed, and consequently virus transmission
      occurs. Transcription from the latency-related (LR) gene is readily detected in
      neurons of trigeminal ganglia (TG) of calves or rabbits latently infected with
      BHV-1. Two micro-RNAs and a transcript encompassing a small open reading frame
      (ORF-E) located within the LR promoter can also be detected in TG of latently
      infected calves. A BHV-1 mutant that contains stop codons near the beginning of
      the first open reading frame (ORF2) within the major LR transcript (LR mutant
      virus) has been characterized. The LR mutant virus does not express ORF2, a
      reading frame that lacks an initiating ATG (reading frame B), and has reduced
      expression of ORF1 during productive infection. The LR mutant virus does not
      reactivate from latency following dexamethasone treatment suggesting that LR
      protein expression regulates the latency-reactivation cycle. Higher levels of
      apoptosis occur in TG neurons of calves infected with the LR mutant viruses when
      compared to wild-type BHV-1 indicating that the anti-apoptotic properties of the
      LR gene is necessary for the latency-reactivation cycle. ORF2 inhibits apoptosis
      and regulates certain viral promoters, in part, because it interacts with three
      cellular transcription factors (C/EBP-alpha, Notch1, and Notch3). Although ORF2
      is important for the latency-reactivation cycle, we predict that other LR gene
      products play a supportive role during life-long latency in cattle.

PMID- 22139603
TI  - Control of HSV-1 latency in human trigeminal ganglia--current overview.
AB  - Although recurrent Herpes simplex virus type 1 (HSV-1) infections are quite
      common in humans, little is known about the exact molecular mechanisms involved
      in latency and reactivation of the virus from its stronghold, the trigeminal
      ganglion. After primary infection, HSV-1 establishes latency in sensory neurons,
      a state that lasts for the life of the host. Reactivation of the virus leads to
      recurrent disease, ranging from relatively harmless cold sores to ocular herpes.
      If herpes encephalitis-often a devastating disease-is also caused by reactivation
      or a new infection, is still a matter of debate. It is widely accepted that
      CD8(+) T cells as well as host cellular factors play a crucial role in
      maintaining latency. At least in the animal model, IFNgamma and Granzyme B
      secretion of T cells were shown to be important for control of viral latency.
      Furthermore, the virus itself expresses factors that regulate its own latency
      reactivation cycle. In this regard, the latency associated transcript, immediate
      early proteins, and viral miRNAs seem to be the key players that control latency
      and reactivation on the viral side. This review focuses on HSV-1 latency in
      humans in the light of mechanisms learned from animal models.

PMID- 22139607
TI  - Diphenyl diselenide ameliorates cognitive deficits induced by a model of
      menopause in rats.
AB  - Ovarian hormone loss contributes to cognitive decline in postmenopausal women.
      Studies have demonstrated a positive role of the level of the element selenium in
      cognitive performance. The present study investigated the effects of the
      synthetic organoselenium compound diphenyl diselenide (PhSe)2 on cognitive
      functions in ovariectomized rats. Ninety-day-old female Wistar rats were
      subjected to ovariectomy (OVX) or Sham operation. One week after surgery, rats
      were orally treated with (PhSe)2 (5 mg/kg, per oral route) or vehicle once a day
      for 30 days. Next, the rats were evaluated in behavioral tests [Morris water maze
      (MWM) and open-field tests] and biochemical [cerebral acetylcholinesterase
      (AChE)] analyses were carried out. In MWM probe trial, (PhSe)2 decreased the
      latency to reach the platform location and increased the number of crossings over
      the platform location, protecting against cognitive impairment induced by OVX.
      Furthermore, (PhSe)2 prevented the stimulation of AChE activity caused by OVX. In
      conclusion, the present study showed a cognition-enhancing effect of (PhSe)2
      treatment for 30 days in ovariectomized rats in the MWM test, which could be
      related to its ability to prevent the stimulation of AChE activity caused by OVX
      in rats. These findings suggest that (PhSe)2 might have a promising role in
      preventing the cognitive decline related to menopause.

PMID- 22139608
TI  - Automated detection of multiple sclerosis candidate regions in MR images: false
      positive removal with use of an ANN-controlled level-set method.
AB  - Our purpose in this study was to develop an automated segmentation scheme for
      multiple sclerosis (MS) lesions in magnetic resonance images using an artificial
      neural network (ANN)-controlled level-set method. Forty-nine slices with T1
      weighted, T2-weighted, and fluid-attenuated inversion recovery images were
      selected from six examinations of three MS patients including 168 MS lesions for
      this study. First, MS lesions were enhanced by background subtraction. Initial
      regions of MS candidates were detected based on a multiple-gray-level
      thresholding technique and a region-growing technique on the subtraction image.
      Then, final regions of MS candidates were determined by application of a proposed
      segmentation method using an ANN-controlled level-set method, which was used for
      reduction of false positives (FPs) as well as more accurate segmentation.
      Finally, all candidate regions were classified into true positive and FP
      candidate regions by use of a support vector machine. As the result of a leave
      one-candidate-out test method, the detection sensitivity for MS lesions increased
      from 64.9 to 75.0% while decreasing the number of FPs per slice from 19.9 to 4.4
      compared with a previous study. The proposed scheme improved the sensitivity and
      the number of FPs in the detection of MS lesions.

PMID- 22139611
TI  - Recent developments in CE and CEC of peptides (2009-2011).
AB  - The review brings a comprehensive survey of the recent developments of high
      performance electroseparation methods in capillary and microchip formats: zone
      electrophoresis, isotachophoresis, isoelectric focusing, affinity
      electrophoresis, electrokinetic chromatography and electrochromatography.
      Applications of these techniques to analysis, isolation, purification and
      physicochemical and biochemical characterization of peptides are described.
      Advances in the investigation of electromigration properties of peptides, and in
      the methodology of their analysis, such as sample preparation, adsorption
      suppression, EOF control and detection, are presented. New developments, in
      particular, CE and CEC modes are reported and several types of their applications
      to peptide analysis are described: conventional qualitative and quantitative
      analysis, determination in complex (bio)matrices, monitoring of chemical and
      enzymatical reactions and physical changes, amino acid, sequence and chiral
      analysis, and peptide mapping of proteins. Some micropreparative peptide
      separations are shown and capabilities of CE and CEC techniques to provide
      relevant physicochemical characteristics of peptides are demonstrated.

PMID- 22139609
TI  - Long-term outcomes in borderline psychopathology: old assumptions, current
      findings, and new directions.
AB  - Borderline personality disorder (BPD) and historical variants of the diagnosis
      were long held to represent an intractable syndrome of psychopathology consisting
      of interpersonal, intrapsychic, and affective disturbances. For years, patients
      labeled "borderline" were regarded pejoratively due at least in part to the lack
      of effective treatments. Prospective data from recent naturalistic follow-along
      studies along with the development of treatments with empirically demonstrated
      efficacy have changed how BPD is viewed. It is now less common to hide the
      diagnosis from the patient, and BPD has become a useful label to guide the
      treatment process and help the patient make sense of his or her suffering.
      Although it is now accepted that BPD is a treatment-responsive disorder and that
      remission is the norm, more work is needed to help patients achieve a higher
      level of functioning, and targeting persistent trait-like features suggests new
      directions for future efforts in treatment development.

PMID- 22139612
TI  - Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins:
      relationship to markers of oxidative stress in men from Auckland, New Zealand.
AB  - There is controversy as to the recommended daily intake of selenium (Se), and
      whether current New Zealand diets are adequate in this nutrient. Various
      functional single-nucleotide polymorphisms (SNPs) polymorphisms may affect the
      efficacy of Se utilisation. These include the glutathione peroxidases GPx1
      rs1050450, GPx4 rs713041, as well as selenoproteins SEPP1 rs3877899, SEL15
      rs5845, SELS rs28665122 and SELS rs4965373. This cross-sectional study measured
      serum Se levels of 503 healthy Caucasian men in Auckland, New Zealand, between
      ages 20-81. The Se distribution was compared with activities of the antioxidant
      enzymes glutathione peroxidase and thioredoxin reductase, and DNA damage as
      measured by the single cell gel electrophoresis assay, both without and with a
      peroxide-induced oxidative challenge. Serum Se was measured using inductively
      coupled plasma-dynamic reaction cell-mass spectrometry, while selenoprotein SNPs
      were estimated using TaqMan((r)) SNP genotyping assays. While antioxidant enzyme
      activities and DNA damage recorded after a peroxide challenge increased with
      increasing serum selenium, the inherent DNA damage levels in leukocytes showed no
      statistically significant relationship with serum selenium. However, these
      relationships and dietary Se requirements at the individual level were modified
      by several different SNPs in genes for selenoproteins. The GPx1 rs1050450 C
      allele was significantly associated with GPx activity. Significant correlations
      between serum Se level and GPX activity were seen with all genotypes except for
      homozygous minor allele carriers, while the GPx1 rs1050450 CT genotype showed the
      highest correlation. Several genotypes showed significant correlations between
      serum Se and TR activity with SEPP1 rs3877899 GG genotype showing the highest
      correlation. A significant decreasing trend in DNA damage with increasing serum
      Se was seen among GPx1 rs1050450 CC and GPx4 rs713041 TT genotype carriers up to
      a serum Se level of 116 and 149 ng/ml, respectively. In the absence of this
      genetic information, we would recommend a serum Se concentration in the region of
      100-150 ng/ml as providing a useful compromise.

PMID- 22139613
TI  - Clinical and electrophysiologic outcome in patients with neovascular glaucoma
      treated with and without bevacizumab.
AB  - PURPOSE: To investigate the clinical and electrophysiologic effect of a single
      intravitreal injection of bevacizumab for neovascular glaucoma (NVG) after
      ischemic central retinal vein occlusion (iCRVO). METHODS: Nineteen eyes from 19
      patients with NVG secondary to iCRVO were randomly allocated to either an
      intravitreal bevacizumab injection and panretinal photocoagulation (PRP) (10
      eyes) or PRP alone (9 eyes). The primary outcome measure was the change in the
      total retinal function 6 months after treatment, demonstrated by full-field
      electroretinography (ERG). Secondary outcomes included visual acuity, intraocular
      pressure (IOP), glaucoma medication, additional IOP-lowering treatment, and the
      presence of ocular neovascularization before treatment, and 1 week, 2 months, and
      6 months after treatment. RESULTS: The regression of ocular neovascularization in
      the bevacizumab/PRP group was confirmed 1 week after injection. Patients in both
      study groups had very poor visual acuity at baseline. This remained unchanged.
      There was no significant difference in the mean IOP between the groups at any
      point in time. The a-wave amplitudes of combined rod-cone response were
      significantly decreased after 6 months in the bevacizumab/PRP group (p=0.028),
      compared with the baseline values. The a- and b-wave amplitudes of combined rod
      cone response and the b-wave amplitudes of the 30-Hz flicker response were also
      markedly reduced compared with the PRP group (-60%, -43%, -47% vs +23%, -36%, 
      16%, respectively). CONCLUSIONS: This study suggests that intravitreal injection
      of bevacizumab is valuable in the treatment of NVG by hastening the resolution of
      neovascularization, while the full-field ERG results indicate that bevacizumab
      may reduce the photoreceptor function in NVG patients.

PMID- 22139614
TI  - Acute mountain sickness and retinal evaluation by optical coherence tomography.
AB  - PURPOSE: Acute mountain sickness (AMS), the commonest form of altitude illness,
      might represent early-stage high altitude cerebral edema (HACE). Optical
      coherence tomography (OCT) was used to evaluate optic nerve head (ONH)
      consequences following a sojourn to extreme altitude. METHODS: This prospective
      study included 4 high-altitude expeditions in Himalayas. Twenty-four eyes of 12
      healthy male climbers underwent baseline and postexpedition complete ophthalmic
      evaluation, including OCT to measure the peripapillary retinal nerve fiber layer
      (RNFL) thickness, ONH parameters, and macular thickness and volume. Lake Louise
      Scoring (LLS) self-report questionnaire was used to estimate AMS severity.
      RESULTS: All mountaineers experienced symptoms of AMS (LLS: 5.1+/-1.1, range 4.0
      7.0). Average peripapillary RNFL thickness showed a significant increase in
      postexpedition examination (94+/-23 um, 47-115), compared with baseline values
      (89+/-19 um, range 45-114) (p=0.034). Superior (p=0.036) and temporal (p=0.010)
      quadrants also showed an increased RNFL thickness following exposure to high
      altitude. Vertical integrated rim area (VIRA) was significantly higher in
      postexpedition examination (0.71+/-0.43 mm(3), 0.14-1.50) than in baseline
      examination (0.51+/-0.26 mm(3), 0.11-1.00) (p=0.002). Horizontal integrated rim
      width was significantly higher in postexpedition examination (1.90+/-0.32 mm(2),
      range 1.37-2.34) than in baseline examination (1.77+/-0.27 mm(2), 1.27-2.08)
      (p=0.004). There was no correlation between LLS and OCT parameters (p>0.05).
      CONCLUSIONS: In climbers with AMS, OCT was able to detect subtle increases in the
      peripapillary RNFL thickness and in some ONH measurements, even in absence of
      HACE and papilledema. These changes might be a sensitive parameter in physiologic
      acclimatization and in the pathogenesis of AMS.

PMID- 22139615
TI  - Intravitreal bevacizumab for choroidal neovascularization secondary to Best
      vitelliform macular dystrophy in a 6-year-old child.
AB  - PURPOSE: To report a young patient with choroidal neovascularization (CNV)
      secondary to Best vitelliform macular dystrophy (BVMD) who recovered good visual
      acuity with intravitreal bevacizumab (IVB). METHODS: A 6-year-old boy was noted
      to have diminution of vision in both eyes. His best-corrected visual acuity
      (BCVA) was 20/40 in the right eye (OD) and 20/160 in the left eye (OS). Detailed
      examination including slit-lamp biomicroscopy, fluorescein angiography, and
      optical coherence tomography (OCT) showed active CNV in OS. Two consecutive IVB
      injections (1.25 mg/0.05 mL) were given in OS. RESULTS: During the follow-up, OD
      showed minimal subretinal fluid on OCT and was treated with one injection of IVB
      (1.25 mg/0.05 mL). At 9 months of follow-up, OS BCVA was 20/50 and OD BCVA 20/30
      with presence of scarred CNV on fundus examination and OCT in both the eyes. No
      drug-related ocular or systemic side effects were encountered. CONCLUSIONS:
      Intravitreal bevacizumab appears to be a promising and cost-effective modality of
      treatment in CNV associated with BVMD with good visual recovery.

PMID- 22139616
TI  - Unilateral retinitis pigmentosa: a proposal of genetic pathogenic mechanisms.
AB  - PURPOSE: To investigate and integrate anatomic and physiologic findings from a
      group of patients who present retinitis pigmentosa affecting just one eye and use
      this information to propose mechanisms of disease pathogenesis. METHODS: This
      prospective cross-sectional study examined 5 patients, all female, from 8 to 60
      years old. The study was conducted in 4 university hospitals. The patients were
      selected according to the characteristics of ocular involvement, notably
      unilateral presentation of similar anatomic and functional abnormalities. Full
      field electroretinogram, fundus photography, fundus autofluorescence, infrared
      imaging, optical coherence tomography, and genetic testing were performed.
      RESULTS: Full-field electroretinogram showed unilateral decrease in amplitude and
      increase in implicit time; autofluorescence showed unilateral areas of decreased
      intensity. The USH2AW4149R mutation was confirmed in one patient. CONCLUSIONS:
      Imaging and functional testing are important in elucidating the unilateral
      pattern of the disease and in monitoring these individuals. Mosaicism or somatic
      mutation may cause unilateral genetic disease presentation.

PMID- 22139617
TI  - In vivo assessment of higher-order aberrations after AcrySof toric intraocular
      lens implantation: a comparative study.
AB  - PURPOSE: To compare higher-order aberrations (HOAs) and optical quality in eyes
      implanted with AcrySof SN60TT toric intraocular lens (IOL) or with non-toric
      AcrySof SN60AT IOL (Alcon Laboratories, Inc., Fort Worth, TX). METHODS: This was
      a prospective, consecutive, nonrandomized, interventional, comparative study. One
      hundred eyes with cataract in 56 patients were included (SN60TT group, n=50;
      SN60AT group, n=50). Patients underwent phacoemulsification through a 2.2-mm
      temporal corneal incision. Postoperative HOAs, point spread function (PSF) and
      modulation transfer function (MTF), residual objective refractive astigmatism,
      and IOL alignment were evaluated using Optical Path Difference (OPD)-Scan II
      (Nidek, Gamagori, Japan). A novel technique to calculate IOL axis alignment was
      introduced. RESULTS: One year postoperatively, no statistical difference in
      corneal, intraocular, and total HOAs, Strehl ratio, and MTF based on HOAs was
      found between groups. Toric IOL patients had a net residual refractive
      astigmatism (M) of 0.44 D+/-0.47; the difference between expected and obtained
      astigmatism (M) was 0.043 D (p=0.16). Toric IOL axis misalignment was 2.65+/-2.39
      degrees and no correlation with HOAs was found. CONCLUSIONS: AcrySof SN60TT
      determines HOAs comparable to the non-toric version providing a good optical
      quality, and predictably corrects corneal cylinder with a stable postoperative
      alignment. The OPD-Scan II might be regarded as a fast and reliable method of
      toric IOL analysis.

PMID- 22139618
TI  - Reproducibility of fluorescein and indocyanine green angiographic assessment for
      RAP diagnosis: a multicenter study.
AB  - PURPOSE: To explore the interobserver agreement in the diagnosis of retinal
      angiomatous proliferation (RAP) using fluorescein (FA) and indocyanine green
      angiographies (ICGA) and to detect which morphologic features of the neovascular
      lesion are associated with RAP diagnosis. METHODS: In this cross-sectional study,
      consecutive patients with newly diagnosed neovascular age-related macular
      degeneration (AMD) evaluated in 8 retina centers were considered. The FA and ICGA
      were obtained in all centers according to a standard protocol, both performed
      either as a static or as a dynamic examination. All images were graded by 2
      observers from different institutions. RESULTS: A total of 201 eyes with
      neovascular AMD of 155 consecutive patients (mean age 76+/-8 years) were
      considered. Overall RAP prevalence was 30% using FA and 26% using ICGA. Patients
      studied with dynamic angiography were twice as likely to be diagnosed with RAP as
      those using static angiography. Interobserver agreement for the overall detection
      of RAP was high using FA (kappa: 0.868; 95% confidence interval [CI]: 0.793
      0.944) and very high using ICGA (kappa: 0.905; 95% CI 0.836-0.974). The agreement
      between the 2 observers tended to be higher for the truncated vessel than for the
      anastomosis in FA as well as in ICGA, but no comparison yielded statistical
      significance (p=0.258 and p=0.584, respectively). CONCLUSIONS: The interobserver
      agreement for RAP detection was very good both using FA and ICGA, but the overall
      detection of RAP was higher for dynamic strategy compared with static one.

PMID- 22139619
TI  - Systematic review and meta-analysis of antibiotic prophylaxis to prevent
      infections from chest drains in blunt and penetrating thoracic injuries.
AB  - BACKGROUND: No consensus exists as to whether antibiotic prophylaxis in tube
      thoracostomy as primary treatment for traumatic chest injuries reduces the
      incidence of surgical-site and pleural cavity infections. METHODS: A systematic
      literature search was performed according to PRISMA guidelines to identify
      randomized clinical trials on antibiotic prophylaxis in tube thoracostomy for
      traumatic chest injuries. Data were extracted by two reviewers using piloted
      forms. Mantel-Haenszel pooled odds ratios (ORs) were calculated with 95 per cent
      confidence intervals (c.i.). RESULTS: Eleven articles were included, encompassing
      1241 chest drains in 1234 patients. Most patients (84.7 per cent) were men, and a
      penetrating injury mechanism was most common (856, 69.4 per cent). A favourable
      effect of antibiotic prophylaxis on the incidence of pulmonary infection was
      found, with an OR for the overall infectious complication rate of 0.24 (95 per
      cent c.i. 0.12 to 0.49). Patients who received antibiotic prophylaxis had an
      almost three times lower risk of empyema than those who did not receive
      antibiotic treatment (OR 0.32, 0.17 to 0.61). A subgroup analysis in patients
      with penetrating chest injuries showed that antibiotic prophylaxis in these
      patients reduced the risk of infection after tube thoracostomy (OR 0.28, 0.14 to
      0.57), whereas in a relatively small blunt trauma subgroup no effect of
      antibiotic prophylaxis after blunt thoracic injury was found. CONCLUSION:
      Infectious complications are less likely to develop when antibiotic prophylaxis
      is administered to patients with thoracic injuries requiring chest drains after
      penetrating injury.

PMID- 22139620
TI  - Addition of alkynes to a gallium bis-amido complex: imitation of transition-metal
      based catalytic systems.
AB  - Acetylene, phenylacetylene, and alkylbutynoates add reversibly to (dpp-bian)Ga
      Ga(dpp-bian) (dpp-bian=1,2-bis[(2,6-diisopropylphenyl)-imino]acenaphthene) to
      give addition products [dpp-bian(R(1)C=CR(2))]Ga-Ga[(R(2)C=CR(1))dpp-bian]. The
      alkyne adds across the Ga-N-C section, which results in new carbon-carbon and
      carbon-gallium bonds. The adducts were characterized by electron absorption, IR,
      and (1)H NMR spectroscopy and their molecular structures have been determined by
      single-crystal X-ray analysis. According to the X-ray data, a change in the
      coordination number of gallium from three [in (dpp-bian)Ga-Ga(dpp-bian)] to four
      (in the adducts) results in elongation of the metal-metal bond by approximately
      0.13 A. The adducts undergo a facile alkynes elimination at elevated
      temperatures. The equilibrium between [dpp-bian(PhC=CH)]Ga-Ga[(HC=CPh)dpp-bian]
      and [(dpp-bian)Ga-Ga(dpp-bian) + 2 PhC=CH] in toluene solution was studied by
      (1)H NMR spectroscopy. The equilibrium constants at various temperatures
      (298<=T<=323 K) were determined, from which the thermodynamic parameters for the
      phenylacetylene elimination were calculated (DeltaG degrees =2.4 kJ mol(-1),
      DeltaH degrees =46.0 kJ mol(-1), DeltaS degrees =146.0 J K(-1) mol(-1)). The
      reactivity of (dpp-bian)Ga-Ga(dpp-bian) towards alkynes permits use as a catalyst
      for carbon-nitrogen and carbon-carbon bond-forming reactions. The bisgallium
      complex was found to be a highly effective catalyst for the hydroamination of
      phenylacetylene with anilines. For instance, with [(dpp-bian)Ga-Ga(dpp-bian)] (2
      mol%) in benzene more than 99% conversion of PhNH(2) and PhC=CH into
      PhN=C(Ph)CH(3) was achieved in 16 h at 90  degrees C. Under similar conditions,
      the reaction of 1-aminoanthracene with PhC=CH catalyzed by (dpp-bian)Ga-Ga(dpp
      bian) formed a carbon-carbon bond to afford 1-amino-2-(1-phenylvinyl)anthracene
      in 99% yield.

PMID- 22139621
TI  - Surrogate decision making for patients with end-stage dementia.
AB  - OBJECTIVE: We aim to explore how health surrogates of patients with dementia
      proceed in decision making, which considerations are decisive, and whether family
      surrogates and professional guardians decide differently. METHODS: We conducted
      an experimental vignette study using think aloud protocol analysis. Thirty-two
      family surrogates and professional guardians were asked to decide on two
      hypothetical case vignettes, concerning a feeding tube placement and a cardiac
      pacemaker implantation in patients with end-stage dementia. They had to verbalize
      their thoughts while deciding. Verbalizations were audio-recorded, transcribed,
      and analyzed according to content analysis. By experimentally changing variables
      in the vignettes, the impact of these variables on the outcome of decision making
      was calculated. RESULTS: Although only 25% and 31% of the relatives gave their
      consent to the feeding tube and pacemaker placement, respectively, 56% and 81% of
      the professional guardians consented to these life-sustaining measures. Relatives
      decided intuitively, referred to their own preferences, and focused on the
      patient's age, state of wellbeing, and suffering. Professional guardians showed a
      deliberative approach, relied on medical and legal authorities, and emphasized
      patient autonomy. Situational variables such as the patient's current behavior
      and the views of health care professionals and family members had higher impacts
      on decisions than the patient's prior statements or life attitudes. CONCLUSIONS:
      Both the process and outcome of surrogate decision making depend heavily on
      whether the surrogate is a relative or not. These findings have implications for
      the physician-surrogate relationship and legal frameworks regarding surrogacy.

PMID- 22139622
TI  - A comparison of cinnarizine and transdermal scopolamine for the prevention of
      seasickness in naval crew:  a double-blind, randomized, crossover study.
AB  - OBJECTIVES: The objective of the study was to compare the efficacy of transdermal
      scopolamine and cinnarizine in the prevention of seasickness and their adverse
      reactions. METHODS: Seventy-six naval crew members participated in a double
      blind, randomized, crossover study. On 2 voyages, they were administered either a
      transdermal scopolamine patch containing 1.5 mg scopolamine and placebo tablets
      or 25-mg cinnarizine tablets and a placebo patch. Subjects completed
      questionnaires for each voyage, reporting on the efficacy of the drugs, the
      severity of their adverse reactions, and the preferred treatment. RESULTS:
      Subjects reported the scopolamine patch to be significantly more effective than
      the cinnarizine tablet (P = 0.029). A moderate to high degree of drowsiness was
      attributed more frequently to cinnarizine than to the scopolamine patch (34% and
      17%, respectively; P < 0.02). Any adverse reaction, to at least a moderate
      degree, was more frequent with cinnarizine (38%) than with the scopolamine patch
      (22%), although the significance of this association was borderline. A
      significantly greater percentage of subjects preferred transdermal scopolamine to
      cinnarizine (41 vs 12%, P < 0.001). CONCLUSIONS: Higher efficacy, a lower rate of
      adverse reactions, and convenience all led the participants of this study to
      prefer the scopolamine patch to cinnarizine. Considering the 2 therapeutic
      options assessed in this study, and in light of the findings of previous studies,
      it is recommended that the scopolamine patch be used as the drug of choice for
      the treatment of seasickness among naval crew in particular and probably also
      among all other sea travelers.

PMID- 22139623
TI  - What factors influence motor complications in Parkinson disease?:  a 10-year
      prospective study.
AB  - The causes and mechanism behind motor complications in Parkinson disease (PD) are
      still a subject of debate. Several factors including age at onset, evolution in
      years, and initial medication can influence the onset and severity of motor
      complications in PD.We studied patients with recent diagnosis of PD who were
      followed up prospectively for 10 years. Analysis included the progression of
      these patients, as measured by the Unified Parkinson Disease Rating Scale scores
      and the presence of motor complications (motors fluctuations, dyskinesias, and
      gait freezing) over time. The patient group was studied as a whole and by
      subgroups classified according to age at onset, initial treatment, and sex.By the
      end of the first decade, most patients exhibited dyskinesias (91%), motor
      fluctuations (62%), and freezing of gait (68%). An association was found between
      several patients' characteristics and presence of motor complications by 5 years,
      though not after 10 years of follow up. The apparition of motor fluctuations was
      mainly related to initial treatment (odds ratio [OR], 3.87). The development of
      dyskinesias was linked to initial treatment (OR, 8.31), age at onset (OR, 0.90),
      and sex (OR, 12.87).

PMID- 22139624
TI  - Value of multiparametric MRI in the work-up of prostate cancer.
AB  - The role of magnetic resonance imaging (MRI) in prostate cancer evaluation is
      controversial and likely underestimated. Technological advances over the past 5
      years have demonstrated that multiparametric MRI, including diffusion-weighted
      imaging (DWI) and dynamic contrast-enhanced MRI, can evaluate the actual tumor
      burden of a newly diagnosed prostate cancer more accurately than sextant biopsy
      protocols. Tumor risk, defined by the D'Amico criteria, hence can be re-evaluated
      by multiparametric MRI. As a result, there is increasing evidence that MRI before
      repeat or even initial biopsy can accurately select patients who require
      immediate biopsies and those in whom biopsy could be deferred. Also, a
      relationship between apparent diffusion coefficient (ADC), calculated from DWI,
      and Gleason score was found. Thus, MRI before biopsy helps to detect high-grade
      tumors to target biopsies within areas of low ADC values. To achieve good
      targeting accuracy, transrectal ultrasound (TRUS)-MRI image registration is
      necessary. Three-dimensional deformable registration is sufficiently accurate to
      match TRUS and MRI volumes with a topographic precision of 1 mm. Real-time MRI
      guided biopsy is another technique under evaluation. Both approaches will allow
      for increasing acceptance of focal therapies, should these techniques be
      validated in the future.

PMID- 22139625
TI  - Targeted therapies in metastatic renal cell carcinoma: overview of the past year.
AB  - During the past half-decade, clinical trials have permitted major progress in
      treatment of metastatic renal cell carcinoma with the first generation of
      targeted therapies (bevacizumab, sunitinib, sorafenib, everolimus, and
      temsirolimus). New targeted agents such as axitinib, tivozanib, and dovitinib,
      all of which are tyrosine kinase inhibitors, have been developed in treatment of
      metastatic renal cell carcinoma. In the same time, more information regarding
      mechanism of disease and drug resistance shed light on new targets and new potent
      agents. We report an overview of the more relevant data published over the past
      year, which may modify the therapeutic landscape of kidney cancer in the near
      future.

PMID- 22139626
TI  - Effects of curcumin on the activities of the enzymes that hydrolyse adenine
      nucleotides in platelets from cigarette smoke-exposed rats.
AB  - The aim of the present study was to investigate the effect of curcumin (Cur) on
      the activity of ectonucleoside triphosphate diphosphohydrolase (CD39), 5'
      nucleotidase (CD73) and adenosine deaminase in platelets of cigarette smoke
      exposed rats. For that purpose, we subjected male Wistar rats to a treatment with
      Cur and cigarette smoke, once a day, 5 days each week, for 30 days. The rats were
      treated by gavage with Cur or corn oil and then exposed to cigarette smoke. The
      experimental procedures were divided into two sets of experiments. In the first,
      the animals were divided into four groups: vehicle (corn oil) or Cur 12.5, 25 or
      50 mg.kg(-1) . In the second, the animals were divided into five groups: vehicle
      (corn oil), smoke, or smoke and Cur 12.5, 25 or 50 mg.kg(-1) . The results showed
      that treatment with Cur significantly prevented the increased adenosine
      triphosphate (ATP) (121%) and adenosine monophosphate (AMP) (159%) and the
      decreased adenosine diphosphate (ADP) (51%) hydrolysis observed in the cigarette
      smoke-exposed rats Our results suggest that those purinergic enzyme alterations
      observed in the cigarette smoke-exposed rats could be related to an excessive
      platelet aggregation and point toward the potential of Cur to modulate purinergic
      signalling and, consequently, regulate the thrombus formation.

PMID- 22139627
TI  - Acheron regulates vascular endothelial proliferation and angiogenesis together
      with Id1 during wound healing.
AB  - RNA binding protein acheron has proved to be either the mediator of integrin
      extracellular matrix interactions or the regulatory factor that participates in
      vertebrate development, cell differentiation and cell death. We report the role
      of acheron in vascular endothelial proliferation, angiogenesis and wound healing
      post-trauma. Co-immunoprecipitation showed that Acheron forms a ternary complex
      with beta1 integrin and Id1 in human umbilical vein endothelial cells following
      stimulation with serious trauma serum. Acheron, vascular endothelial growth
      factor (VEGF), and beta1 integrin mRNA expression was apparently inhibited, and
      capillary density and wound healing rate also were reduced in Id1-deficient mice
      trauma model. Acheron together with Id1 significantly induces VEGF, not CD105
      level inhibition by serious trauma serum for 24 h. In conclusion, we have
      demonstrated that acheron may be an effective mediator of promoting endothelial
      proliferation, angiogenesis and wound healing probably by regulating VEGF
      together with Id1.

PMID- 22139629
TI  - Adolescent and young adult oncology comes of age: researchers seek to provide
      better resources for this patient group.

PMID- 22139630
TI  - Dana-Farber seeks to reach young adult cancer patients.

PMID- 22139631
TI  - Researchers report discoveries in cancer progression and rare skin and pancreatic
      cancers.

PMID- 22139634
TI  - Oxygen atom transfer from a trans-dioxoruthenium(VI) complex to nitric oxide.
AB  - In aqueous acidic solutions trans-[Ru(VI)(L)(O)(2)](2+) (L=1,12-dimethyl-3,4:9,10
      dibenzo-1,12-diaza-5,8-dioxacyclopentadecane) is rapidly reduced by excess NO to
      give trans-[Ru(L)(NO)(OH)](2+). When <=1 mol equiv NO is used, the intermediate
      Ru(IV) species, trans-[Ru(IV)(L)(O)(OH(2))](2+), can be detected. The reaction of
      [Ru(VI)(L)(O)(2)](2+) with NO is first order with respect to [Ru(VI)] and [NO],
      k(2)=(4.13+/-0.21)*10(1) M(-1) s(-1) at 298.0 K. DeltaH(?) and DeltaS(?) are
      (12.0+/-0.3) kcal mol(-1) and -(11+/-1) cal mol(-1) K(-1), respectively. In
      CH(3)CN, DeltaH(?) and DeltaS(?) have the same values as in H(2)O; this suggests
      that the mechanism is the same in both solvents. In CH(3)CN, the reaction of
      [Ru(VI)(L)(O)(2)](2+) with NO produces a blue-green species with lambda(max) at
      approximately 650 nm, which is characteristic of N(2)O(3). N(2)O(3) is formed by
      coupling of NO(2) with excess NO; it is relatively stable in CH(3)CN, but
      undergoes rapid hydrolysis in H(2)O. A mechanism that involves oxygen atom
      transfer from [Ru(VI)(L)(O)(2)](2+) to NO to produce NO(2) is proposed. The
      kinetics of the reaction of [Ru(IV)(L)(O)(OH(2))](2+) with NO has also been
      investigated. In this case, the data are consistent with initial one-electron O(
      ) transfer from Ru(IV) to NO to produce the nitrito species
      [Ru(III)(L)(ONO)(OH(2))](2+) (k(2)>10(6) M(-1) s(-1)), followed by a reaction
      with another molecule of NO to give [Ru(L)(NO)(OH)](2+) and NO(2)(-) (k(2)=54.7
      M(-1) s(-1)).

PMID- 22139633
TI  - Remembering first impressions: effects of intentionality and diagnosticity on
      subsequent memory.
AB  - People rely on first impressions every day as an important tool to interpret
      social behavior. While research is beginning to reveal the neural underpinnings
      of first impressions, particularly through understanding the role of dorsal
      medial prefrontal cortex (dmPFC), little is known about the way in which first
      impressions are encoded into memory. This is surprising because first impressions
      are relevant from a social perspective for future interactions, requiring that
      they be transferred to memory. The present study used a subsequent-memory
      paradigm to test the conditions under which the dmPFC is implicated in the
      encoding of first impressions. We found that intentionally forming impressions
      engages the dmPFC more than does incidentally forming impressions, and that this
      engagement supports the encoding of remembered impressions. In addition, we found
      that diagnostic information, which more readily lends itself to forming trait
      impressions, engages the dmPFC more than does neutral information. These results
      indicate that the neural system subserving memory for impressions is sensitive to
      consciously formed impressions. The results also suggest a distinction between a
      social memory system and other explicit memory systems governed by the medial
      temporal lobes.

PMID- 22139635
TI  - Leukocyte adhesion deficiency-I variant syndrome (LAD-Iv, LAD-III): molecular
      characterization of the defect in an index family.
AB  - Leukocyte adhesion deficiencies are rare clinical syndromes of impaired host
      defense that provide novel insights into regulation of immune and inflammatory
      responses. Leukocyte adhesion deficiency (LAD)-I variant (LAD-Iv), also called
      LAD-III, is a unique disorder in which inside-out signaling of beta1, beta2, and
      beta3 integrins on leukocytes and platelets is disrupted, leading to impaired
      cellular adhesion, recurrent infections, and bleeding. We originally reported the
      second patient with this disorder to be identified and characterized the adhesive
      deficiencies and functional phenotype of this subject's leukocytes. Here, we show
      that the molecular defect in this index subject is a new mutation in FERMT3
      (KINDLIN-3) which encodes KINDLIN-3, a cytoskeletal protein that interacts with
      the cytoplasmic tails of beta1, beta2, and beta3 integrins and is required for
      inside-out and outside-in signaling of these heterodimers. We also report
      clinical features and previously unrecognized defects in cells from a new
      patient, a sibling of the original subject that we described who carries the same
      FERMT3 mutation. Mutations in FERMT3 have now been shown to be the basis for LAD
      Iv/LAD-III in each of the four original patients or families that established
      this syndrome, including the family that we describe.

PMID- 22139636
TI  - The development of a rat in vitro model of spinal cord injury demonstrating the
      additive effects of Rho and ROCK inhibitors on neurite outgrowth and myelination.
AB  - It is currently thought that treatment for spinal cord injury (SCI) will involve
      a combined pharmacological and biological approach; however, testing their
      efficacy in animal models of SCI is time-consuming and requires large animal
      cohorts. For this reason we have modified our myelinating cultures as an in vitro
      model of SCI and studied its potential as a prescreen for combined therapeutics.
      This culture comprises dissociated rat embryonic spinal cord cells plated onto a
      monolayer of astrocytes, which form myelinated axons interspaced with nodes of
      Ranvier. After cutting the culture, an initial cell-free area appears
      persistently devoid of neurites, accompanied over time by many features of SCI,
      including demyelination and reduced neurite density adjacent to the lesion, and
      infiltration of microglia and reactive astrocytes into the lesioned area. We
      tested a range of concentrations of the Rho inhibitor C3 transferase (C3) and
      ROCK inhibitor Y27632 that have been shown to promote SCI repair in vivo. C3
      promoted neurite extension into the lesion and enhanced neurite density in
      surrounding areas but failed to induce remyelination. In contrast, while Y27632
      did not induce significant neurite outgrowth, myelination adjacent to the lesion
      was dramatically enhanced. The effects of the inhibitors were concentration
      dependent. Combined treatment with C3 and Y27632 had additive affects with an
      enhancement of neurite outgrowth and increased myelination adjacent to the
      lesion, demonstrating neither conflicting nor synergistic effects when
      coadministered. Overall, these results demonstrate that this culture serves as a
      useful tool to study combined strategies that promote CNS repair.

PMID- 22139638
TI  - Good practices and health policy analysis in European sports stadia: results from
      the 'Healthy Stadia' project.
AB  - Sport plays an important role within society and sports stadia provide
      significant settings for public health strategies. In addition to being places of
      mass gathering, stadia are often located in less affluent areas and are
      traditionally attended by 'harder to reach' communities. Unfortunately sports
      stadia and the clubs they host are rarely perceived as places that promote
      healthy lifestyles. Fast food, alcohol and tobacco are commonly advertized,
      served and consumed during sports games giving the spectators and TV fans
      contradictory messages concerning healthy choices. As part of a wider programme
      of work part-funded by the European Union, a study was therefore designed to
      explore current 'good practice' relating to positive health interventions in
      sports stadia across a number of European countries. Using a specially designed
      questionnaire, information about health policies and good practices relating to
      food offerings in stadia, physical activity promotion among local communities,
      tobacco policy, positive mental health initiatives, environmental sustainability
      practices and social responsibility policies were collected in 10 European
      countries (England and Northern Ireland, Finland, Georgia, Greece, Ireland,
      Italy, Latvia, Poland, Spain and Sweden) involving 88 stadia. The audit results
      show that stadia health policies differ considerably between specific countries
      and sports. Based on the literature analysed, the examples of good practices
      collected through the study, and the subsequent instigation of a European Healthy
      Stadia Network, it shows that there is considerable potential for stadia to
      become health promoting settings.

PMID- 22139637
TI  - Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP
      activated protein kinase.
AB  - Strategies to prevent and treat obesity aim to decrease energy intake and/or
      increase energy expenditure. Regarding the increase of energy expenditure, two
      key intracellular targets may be considered (1) mitochondrial oxidative
      phosphorylation, the major site of ATP production, and (2) AMP-activated protein
      kinase (AMPK), the master regulator of cellular energy homeostasis. Experiments
      performed mainly in transgenic mice revealed a possibility to ameliorate obesity
      and associated disorders by mitochondrial uncoupling in metabolically relevant
      tissues, especially in white adipose tissue (WAT), skeletal muscle (SM), and
      liver. Thus, ectopic expression of brown fat-specific mitochondrial uncoupling
      protein 1 (UCP1) elicited major metabolic effects both at the cellular/tissue
      level and at the whole-body level. In addition to expected increases in energy
      expenditure, surprisingly complex phenotypic effects were detected. The
      consequences of mitochondrial uncoupling in WAT and SM are not identical, showing
      robust and stable obesity resistance accompanied by improvement of lipid
      metabolism in the case of ectopic UCP1 in WAT, while preservation of insulin
      sensitivity in the context of high-fat feeding represents the major outcome of
      muscle UCP1 expression. These complex responses could be largely explained by
      tissue-specific activation of AMPK, triggered by a depression of cellular energy
      charge. Experimental data support the idea that (1) while being always activated
      in response to mitochondrial uncoupling and compromised intracellular energy
      status in general, AMPK could augment energy expenditure and mediate local as
      well as whole-body effects; and (2) activation of AMPK alone does not lead to
      induction of energy expenditure and weight reduction.

PMID- 22139639
TI  - Use of carotid intima-media thickness regression to guide therapy and management
      of cardiac risks.
AB  - OPINION STATEMENT: Although carotid intima-media thickness (IMT) has been broadly
      used as a tool to evaluate cardiovascular risk, its role as a surrogate endpoint
      is still debated. The main issue is the fact that no study has ever been powered
      to show a relationship between changes in carotid IMT during follow-up and
      cardiovascular events. A meta-analysis of existing clinical studies was performed
      to investigate this relationship but it failed to demonstrate a predictive role
      of regression in carotid IMT for cardiovascular events. The reasons for the lack
      of a clear evidence for a predictive role of IMT progression are unknown but are
      likely multifactorial. Firstly, it may depend on the fact that this index is not
      a pure atherosclerosis index. Second, carotid atherosclerosis does not always
      reflect coronary atherosclerosis. Furthermore, methodologic problems related to
      intra- and interobserver variability make this index not adequately reproducible
      when tracking the progression of carotid atherosclerosis. A further meta-analysis
      based on individual patient data, instead of published data, has been planned to
      better address the predictive role of IMT. Lastly, in the future, the variability
      of ultrasound measurements of carotid IMT are likely to be reduced by further
      development of automatic calculation of this index by magnetic resonance imaging.

PMID- 22139640
TI  - Pharmacokinetics of aconitine in rat skin after oral and transdermal gel
      administrations.
AB  - The purpose of this study was to evaluate percutaneous penetration and
      arrhythmogenic effects of aconitine after transdermal administration, compared
      with the oral route. Skin penetration of aconitine was tested by a microdialysis
      technique in rats and in vivo recovery was determined by retrodialysis. After
      oral and transdermal administration of aconitine, dialysate was sampled at 20 min
      intervals until the end of the experiment for the determination of concentration
      of aconitine in skin. Blood samples were collected and analyzed using a validated
      HPLC-MS/MS method. In addition, we concurrently recorded the electrocardiogram
      (ECG). The in vivo recovery of aconitine in the skin was calculated to be 39.59%.
      The C(max) values for aconitine absorbed into the skin after oral and transdermal
      administration were 1.51 +/- 0.53 and 2723.8 +/- 848.8 ng/mL, respectively, and
      within the plasma, 215.86 +/- 79.29 and 20.92 +/- 3.15 ng/mL. The C(max) value
      for the plasma concentration of aconitine after oral administration was
      approximately 10 times higher than with the transdermal route. For oral
      administration, the ECG revealed various types of arrhythmias at a period of
      T(max) , which is normal in transdermal gel administration. These results
      indicate that transdermal aconitine gel is a safe formulation that can deliver
      the drug in sufficient amounts and safe concentrations to produce therapeutic
      action in rats.

PMID- 22139641
TI  - Is coagulation factor VIII a useful marker for colorectal carcinoma?
AB  - BACKGROUND AND OBJECTIVE: Increased thromboembolic events are well known in
      patients suffering from malignant diseases. In the following pilot study, we
      investigated the usefulness of coagulation factor VIII (FVIII) as a possible
      prognostic marker in patients with colorectal carcinoma (CRC). METHODS: Plasma
      FVIII levels were measured in 79 patients with CRC, correlated with tumor
      characteristics, and compared with normal ranges of blood group (BG) 0 and BG
      A/AB/B and with 19 control patients. RESULTS: In CRC patients mean FVIII levels
      were elevated compared with controls (BG 0: p=0.283, BG A/AB/B: p=0.001) and
      normal ranges. Interestingly, mean FVIII levels varied significantly in different
      blood groups (p=0.002). UICC stage I CRC patients presented with mean FVIII
      plasma levels within normal ranges, whereas UICC stage II-IV CRC patients
      presented with elevated FVIII plasma levels. In BG A/AB/B a significantly
      elevated FVIII level was found in G2 compared with G1 tumors (p< 0.001). Patients
      with elevated carcinoembryonic antigen also showed significantly elevated FVIII
      levels (p=0.050). FVIII levels at time of surgery did not correlate with survival
      within the first 2 years following surgery. CONCLUSION: In this pilot study, we
      demonstrated that FVIII plasma levels are elevated in patients with CRC and
      affected by T-stage and differentiation of the tumor. Whether FVIII is a clinical
      useful marker needs to be tested in a larger cohort.

PMID- 22139642
TI  - Vascular endothelial growth factor (VEGF) +936 C/T gene polymorphism and gastric
      cancer risk: appraisal of a recent meta-analysis.

PMID- 22139643
TI  - Prognostic role of C-reactive protein in breast cancer: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Recent studies have shown that C-reactive protein (CRP) may be
      associated with breast cancer. The purpose of this study is to summarize the
      predictive role of CRP for survival in breast cancer as shown in all available
      studies worldwide. METHODS: Related studies were identified and evaluated for
      quality through multiple search strategies. Data were collected from studies
      comparing overall, cancer-specific, and disease-free survival (OS, CSS, and DFS)
      in patients with elevated CRP levels and those having lower levels. Studies were
      pooled, and combined hazard ratios (HRs) of CRP for survival were calculated.
      RESULTS: A total of 10 studies (n=4,502) were included for this meta-analysis (9
      for OS, 3 for CSS, and 3 for DFS). For overall and disease-free survival, the
      pooled HRs of CRP were significant at 1.62 (95% confidence interval [95% CI],
      1.20-2.18) and 1.81 (95% CI, 1.44-2.26), respectively. For cancer-specific
      survival, the pooled HR in higher CRP expression in breast cancer was 2.08 (95%
      CI, 1.48-2.94), which could strongly predict poorer survival in breast cancer.
      CONCLUSIONS: CRP has a critical prognostic value in patients with breast cancer
      as an inflammation biomarker.

PMID- 22139644
TI  - KRAS and BRAF mutation status in patients with sporadic colorectal cancer: data
      from two different Mediterranean countries.

PMID- 22139645
TI  - Proteolytic profile of cysteine proteases and inhibitors determines tumor cell
      phenotype in squamous cell carcinoma of the head and neck.
AB  - The hypothesis was tested that a specific pattern in the cysteine
      cathepsin/inhibitor ratio is associated with the development of more aggressive
      tumor cell phenotypes in squamous cell carcinoma of the head and neck (SCCHN).
      For this purpose commercially available ELISAs were used to determine the
      concentrations of cysteine cathepsins B and L and their inhibitors, stefins A and
      B, in cytosols of nontumorous mucosa and primary tumors from 92 patients. Using
      the stefin A concentration difference in matched pairs of tissue samples as a
      stratifying variable, 53 cases were found to be upregulated (higher
      concentrations in tumor samples than in nontumorous mucosa) and 39 cases
      downregulated. Disease recurrence was more frequent in the downregulated group
      than in the upregulated group (35.9% vs 11.3%, p=0.009), which resulted in
      significantly different 5-year disease-free survival rates (61.2% vs 88%,
      p=0.004). The consistency of these results was confirmed by repeating the
      analysis in an independent group of patients (the reference group). The presented
      results suggest that in patients with SCCHN, specific patterns in the proteolytic
      profile of cysteine proteases and their inhibitors are associated with the
      development of distinctly aggressive tumor cell phenotypes and are of prognostic
      value.

PMID- 22139646
TI  - Differences in 5-hydroxytryptamine-3B haplotype frequencies between Asians and
      Caucasians.
AB  - BACKGROUND: The 5-hydroxytryptamine (5-HT3) receptor is a ligand-operated ion
      channel with five different receptor subunits (5-HT3A, B, C, D, and E) found in
      humans. Activation of 5-HT3 receptors influences various effects such as drug
      induced emesis and causes behavioral problems such as anxiety, depression and
      cognitive disorders. To explore interethnic differences in the response to 5-HT3
      antagonists, we studied haplotype frequencies in the gene encoding the 5-HT3B
      receptor in Asians and Caucasians. METHODS: Three single nucleotide polymorphisms
      (SNPs) of the 5-HT3B receptor gene, i.e., deletion AAG at the 5'-UTR position,
      18792A>G at the intron position, and 46698G>A at the 3' near gene position, were
      selected and genotyped in 165 Indonesian cancer patients and 188 Caucasian
      healthy volunteers. Haplotypes were set with gPlink, whereas the differences in
      haplotype frequencies between Indonesians and Caucasians were compared using
      multivariate analysis. RESULTS: The haplotype profiles based on the deletion AAG,
      18792A>G and 46698G>A were AAGAA, AAGAG, AAGGG, and deletion AG in both
      Indonesians and Caucasians. The frequency of the AAGAG haplotype was 54.8% in
      Indonesians and 39.9% in Caucasians (p<0.05). The frequency of the AAGGG
      haplotype was 14.3% in Indonesians and 29.3% in Caucasians. Moreover, there were
      significant differences in the frequencies of haplotype pairs between Indonesians
      and Caucasians (p<0.001). CONCLUSION: Indonesian cancer patients had
      significantly different AAGAG and AAGGG haplotype frequencies of the gene
      encoding the 5-HT3B receptor compared to healthy Caucasians. This finding could
      be useful for understanding interethnic differences in the response to drugs
      targeting the 5-HT3B receptor in cancer-treatment-related emesis.

PMID- 22139647
TI  - MMP-9 overexpression due to TIMP-1 and RECK underexpression is associated with
      prognosis in prostate cancer.
AB  - BACKGROUND: Extracellular matrix homeostasis is strictly maintained by a
      coordinated balance between the expression of metalloproteinases (MMPs) and their
      inhibitors. The purpose of this study was to investigate whether the expression
      of MMP-9 and its specific inhibitors, TIMP-1 and RECK, are expressed in a
      reproducible, specific pattern and if the profiles are related to prognosis and
      clinical outcome in prostate cancer (PC). METHODS: MMP-9, TIMP-1, and RECK
      expression levels were analyzed by quantitative real-time polymerase chain
      reaction (qRT-PCR) in fresh-frozen malignant tissue specimens collected from 79
      patients with clinically localized PC submitted to radical prostatectomy (RP).
      Frozen benign prostatic tissue from another 10 men with prostate cancer, also
      submitted to RP, was analyzed to determine if the profile of gene expression was
      maintained. The control group consisted of 11 patients with benign prostate
      hyperplasia (BPH). RESULTS: In the tumor samples, MMP-9 was overexpressed by 9.2
      times, and TIMP-1 and RECK were underexpressed (0.75 and 0.80 times,
      respectively). Overexpression of MMP-9 was significantly related to PSA levels
      above 10 ng/mL (p=0.033). In addition, MMP-9 overexpression was related to
      biochemical recurrence, with a marginal statistical significance (p=0.089). MMP-9
      was also overexpressed in benign tissues of patients with PC, as were TIMP-1 and
      RECK, in contrast to their underexpression in tumor samples. CONCLUSION: Our
      results show that MMP-9 is overexpressed and its negative regulators are
      underexpressed in PC tissue, emphasizing a possible role of MMP-9 in the
      carcinogenesis process. Additionally, we noticed a relationship between MMP-9
      overexpression and increased levels of PSA, an important prognostic factor. In
      benign tissue adjacent to tumors, the MMP-9 equilibrium is likely maintained
      because the expression of its negative regulators is preserved.

PMID- 22139649
TI  - An overview of DNA typing methods for human identification: past, present, and
      future.
AB  - This chapter presents a brief introduction to the historical development of
      current technologies used in DNA analysis for human identification. The text
      describes the development of the PCR and short tandem repeats along with
      subsequent advances in instrumentation such as real-time PCR and capillary
      electrophoresis. These techniques have brought about a revolution in DNA typing
      methods through increased efficiency and the application of multiplex
      fluorescence detection. More recently the development of new STR based typing
      methods utilizing mini- and Y-STR PCR multiplexes has increased the flexibility
      of the investigator, permitting the analysis of inhibited and degraded DNA.
      Future directions for DNA typing are also discussed, including the development of
      methods for touch samples based on low copy DNA analysis and the determination of
      tissue/cell type.

PMID- 22139648
TI  - Retrospective analysis of antitumor effects of zoledronic acid in breast cancer
      patients with bone-only metastases.
AB  - BACKGROUND: Bisphosphonates have been used successfully in the treatment of
      hypercalcemia and to reduce skeletal complications of bone metastasis, but have
      not been shown to prevent bone metastasis or to prolong survival time in
      metastatic breast cancer patients. The aim of this study was to determine whether
      the progression-free survival (PFS) and overall survival (OS) of patients with
      bone-only breast cancer metastasis differed based on whether patients received
      zoledronic acid, pamidronate, or no bisphosphonate upon diagnosis of their
      metastases. PATIENTS AND METHODS: We retrospectively identified 314 patients
      diagnosed with bone-only metastasis at the time of initial staging or who
      developed bone metastasis as the first recurrence site during follow-up from
      January 1, 1997 to December 31, 2008, at The MD Anderson Cancer Center.
      Univariate and multivariate Cox hazards models were used to assess the effects of
      each treatment on PFS and OS. RESULTS: Patients who had more than 1 bone
      metastasis and Eastern Cooperative Oncology Group (ECOG) performance status of 2
      and 3 were more likely to receive zoledronic acid in this analysis. Compared with
      no bisphosphonate use, the use of zoledronic acid was not significantly
      associated with longer PFS (hazard ratio [HR] = 0.72, P = .058 in univariate
      analysis, and HR = 0.80, P = .235 in multivariate analysis) nor with longer OS
      (HR = 1.04, P = .863 in univariate analysis and HR = 1.34, P = .192 in
      multivariate analysis). CONCLUSION: Our study demonstrates that for patients with
      bone-only metastases, zoledronic acid did not prolong PFS or OS. In patients with
      bone-only metastasis, we could not demonstrate antitumor effects of zoledronic
      acid.

PMID- 22139650
TI  - Capillary electrophoresis and 5-channel LIF detection of a 26plex autosomal STR
      assay for human identification.
AB  - Multiplex polymerase chain reaction (PCR) is a common method used for DNA typing
      in forensic and paternity cases. There are numerous commercial short tandem
      repeat (STR) multiplex assays currently available to the forensic community.
      These assays amplify the core Combined DNA Index System (CODIS) STR loci for
      entry into the US. DNA database. Additional non-CODIS loci, which are considered
      genetically unlinked to the CODIS loci, can be useful in resolving challenging
      cases such as missing persons and mass disaster victim identification, paternity
      testing, and immigration testing. An STR multiplex has been successfully
      developed with 25 non-CODIS autosomal loci plus the sex-typing locus amelogenin
      for a total of 26 loci in a single 26plex amplification reaction. This chapter
      will focus on the preparation and the use of the 26plex assay with DNA samples
      for the purpose of human identification.

PMID- 22139651
TI  - Capillary electrophoresis of miniSTR markers to genotype highly degraded DNA
      samples.
AB  - The amplification of short tandem repeat (STR) markers throughout the human
      nuclear DNA genome are used to associate crime scene evidence to the
      perpetrator's profile in criminal investigations. For highly challenged or
      compromised materials such as stains exposed to the elements, skeletal remains
      from missing persons cases, or fragmented and degraded samples from mass
      disasters, obtaining a full STR profile may be difficult if not impossible. With
      the introduction of short amplicon STR or "miniSTR" typing, it is possible to
      obtain STR genetic information from highly challenged samples without the need to
      sequence the hypervariable regions of the mitochondrial DNA (mtDNA) genome. Non
      Combined DNA Index System (CODIS) STR markers have been developed to obtain
      information beyond the core CODIS loci. This chapter will focus on the steps
      necessary to prepare and use one of the non-CODIS (NC) multiplexes, NC01 (Coble
      and Butler 2005), for analysis on capillary electrophoresis instrumentation.

PMID- 22139652
TI  - Interpretation guidelines of a standard Y-chromosome STR 17-plex PCR-CE assay for
      crime casework.
AB  - Y-STR analysis is an invaluable tool to examine evidence in sexual assault cases
      and in other forensic casework. Unambiguous detection of the male component in
      DNA mixtures with a high female background is still the main field of application
      of forensic Y-STR haplotyping. In the last years, powerful technologies including
      a 17-locus multiplex PCR assay have been introduced in the forensic laboratories.
      At the same time, statistical methods have been developed and adapted for
      interpretation of a nonrecombining, linear marker as the Y-chromosome which shows
      a strongly clustered geographical distribution due to the linear inheritance and
      the patrilocality of ancestral groups. Large population databases, namely the Y
      STR Haplotype Reference Database (YHRD), have been established to assess the
      evidentiary value of Y-STR matches by means of frequency estimation methods
      (counting and extrapolation).

PMID- 22139653
TI  - Capillary electrophoresis of an X-chromosome STR decaplex for kinship deficiency
      cases.
AB  - During the two last decades, STR markers located on the autosomes have been
      gaining relevance and have nearly replaced the use of other type of markers in
      most cases of genetic identification, paternity testing, as well as in other
      situations of kinship analysis. Nevertheless, in some complex cases,
      independently of the number of polymorphisms being typed, autosomal markers
      convey very little information. Depending on the parentage constellation
      available for analysis, as well as the gender of the subjects, this problem can
      sometimes be solved by using markers that have different modes of transmission.
      Therefore, most forensic laboratories are nowadays prepared to analyse lineage
      markers (Y chromosome and mtDNA) and many have recently set up methods for the
      analysis of X-STRs. In the present chapter, a method is described for the typing
      of ten X chromosome-specific markers in a single PCR amplification reaction,
      followed by capillary electrophoresis separation and fluorescent detection in an
      ABI Genetic Analyser apparatus. This typing strategy was developed and optimized
      for the simultaneous amplification of ten X-linked specific STRs well distributed
      along the chromosome: DXS8378, DXS9902, DXS7132, DXS9898, DXS6809, DXS6789,
      DXS7133, GATA172D05, GATA31E08 and DXS7423.

PMID- 22139654
TI  - A 48-plex autosomal SNP GenPlexTM assay for human individualization and
      relationship testing.
AB  - SNPs are being increasingly used by forensic laboratories. Different platforms
      have been developed for SNP typing. We describe the GenPlexTM HID system
      protocol, a new SNP-typing platform developed by Applied Biosystems where 48 of
      the 52 SNPforID SNPs and amelogenin are included. The GenPlexTM HID system
      protocol has been successfully tested by a number of forensic laboratories using
      both ordinary and forensic samples.

PMID- 22139655
TI  - Typing of 49 autosomal SNPs by single base extension and capillary
      electrophoresis for forensic genetic testing.
AB  - We describe a method for simultaneous amplification of 49 autosomal single
      nucleotide polymorphisms (SNPs) by multiplex PCR and detection of the SNP alleles
      by single base extension (SBE) and capillary electrophoresis. All the SNPs may be
      amplified from only 100 pg of genomic DNA and the length of the amplicons range
      from 65 to 115 bp. The high sensitivity and the short amplicon sizes make the
      assay very suitable for typing of degraded DNA samples, and the low mutation rate
      of SNPs makes the assay very useful for relationship testing. Combined, these
      advantages make the assay well suited for disaster victim identifications, where
      the DNA from the victims may be highly degraded and the victims are identified
      via investigation of their relatives. The assay was validated according to the
      ISO 17025 standard and used for routine case work in our laboratory.

PMID- 22139656
TI  - A 34-plex autosomal SNP single base extension assay for ancestry investigations.
AB  - Ancestry inference based on autosomal markers remains a niche approach in
      forensic analysis: most laboratories feel more secure with a review of the
      cumulative STR profile frequencies in a range of relevant populations with the
      possible additional analysis of mitochondrial and/or Y-chromosome variability.
      However, a proportion of autosomal single nucleotide polymorphisms (SNPs) show
      very well-differentiated allele frequencies among global population-groups.
      Furthermore, such ancestry informative marker SNPs (AIM-SNPs) lend themselves to
      relatively straightforward typing with short-amplicon PCR and multiplexed single
      base extension reactions using the same capillary electrophoresis detectors
      required for the sequencing and STR genotyping of mainstream forensic markers. In
      this chapter, we describe a 34 AIM-SNP multiplex that is robust enough for the
      analysis of challenging, often highly degraded DNA typical of much of routine
      forensic casework. We also outline in detail the in-silico procedures necessary
      for collecting parental population reference data from the SPSmart SNP databases
      and performing ancestry inference of single AIM-SNP profiles or large-scale
      population data using the companion ancestry analysis website of Snipper. Two
      casework examples are described that show, in both cases, that an inference of
      likely ancestry using AIM-SNPs helped the identification of highly degraded
      skeletal material.

PMID- 22139657
TI  - SNaPshot(r) minisequencing analysis of multiple ancestry-informative Y-SNPs using
      capillary electrophoresis.
AB  - This protocol describes a strategy for analyzing phylogenetic Y-SNPs in a
      hierarchical multiplex assay by utilizing the SNaPshot((r)) Multiplex System.
      Step by step, the protocol assists in the appropriate selection of SNPs, the
      primer design, the set up of PCR/SBE reactions as well as in the analysis of the
      results. Furthermore, a forensic approach is highlighted, in which the most
      probable ancestry of an unknown male DNA is inferred by the geographical
      distribution of the assigned Y-SNP haplogroup.

PMID- 22139658
TI  - Capillary electrophoresis of 38 noncoding biallelic mini-Indels for degraded
      samples and as complementary tool in paternity testing.
AB  - This work describes the main advantages and the steps involved in the
      optimization of a multiplex system able to characterize 38 noncoding biallelic
      Insertion Deletion Polymorphisms(Indels). With this methodology, all markers are
      amplified in a single PCR, using short amplicons (up to 160 bp) in order to
      improve its performance in degraded samples. Alleles are easily detected using
      capillary electrophoresis.The Indel multiplex typing strategy here described has
      the same desirable characteristics of forensic SNP assays, including genetic
      markers (a) with low mutation rates, increasing their usefulness in some kinship
      cases where few or single incompatibilities can be explained by mutation, and (b)
      that can be typed using a short amplicon strategy, increasing their usefulness in
      cases where degraded samples are available. Moreover, this approach uses simple
      and well-established methodologies already applied in forensic STR assays.

PMID- 22139659
TI  - Capillary electrophoresis of an 11-plex mtDNA coding region SNP single base
      extension assay for discrimination of the most common Caucasian HV1/HV2 mitotype.
AB  - The typing of single nucleotide polymorphisms (SNPs) located throughout the human
      mitochondrial genome assists in resolving individuals with an identical HV1/HV2
      haplotype. A set of 11 sites which were selected for distinguishing individuals
      of a common Western European Caucasian HV1/HV2 mitotype was incorporated into a
      single base extension (SBE) assay. The assay was optimized for multiplex
      detection of sequence polymorphisms at positions 3010, 4793, 10211, 5004, 7028,
      7202, 16519, 12858, 4580, 477, and 14470 in the mitochondrial genome. PCR primers
      were designed to allow for multiplex amplification of unique regions in the
      mitochondrial genome followed by an 11-plex SBE reaction using the SNaPshot((r))
      reagent kit. Separation and detection can be accomplished with a capillary-based
      electrophoresis platform commonly found in most forensic laboratories.

PMID- 22139660
TI  - Capillary electrophoresis of a multiplex reverse transcription-polymerase chain
      reaction to target messenger RNA markers for body fluid identification.
AB  - The analysis of cell-specific mRNA expression is a promising new method for the
      identification of body fluids. A number of mRNA markers have been identified for
      the forensically most relevant body fluids: blood, saliva, semen, vaginal
      secretions, and menstrual blood. Apart from a significant improvement in
      specificity compared to conventional protein-based methods, other important
      advantages of body fluid identification by mRNA profiling include the possibility
      of simultaneously isolating RNA and DNA from the same piece of stain and the
      ability to multiplex numerous RNA markers for the identification of one or
      several body fluids. RNA profiling can be incorporated into current DNA analysis
      pipelines.

PMID- 22139661
TI  - DNA extraction from aged skeletal samples for STR typing by capillary
      electrophoresis.
AB  - STR analysis of DNA extracted from skeletal samples can play an important role in
      the identification of missing persons. Here we present a method for the
      extraction of DNA from skeletal samples involving complete demineralization and
      digestion of the sample, followed by purification by silica binding. This method,
      together with the multiplex STR typing approach also presented, has proven highly
      successful in the recovery of DNA profiles from degraded, aged skeletal remains
      from a wide range of environmental contexts. The methodological steps presented
      include bone decontamination and grinding, DNA extraction, repurification in the
      case of highly inhibited samples, quantification, STR multiplex amplification,
      and profile reporting guidelines. However, the conditions applied for
      amplification and the criteria for allele calling and profile submission must be
      based on the results of each laboratory's internal validation experiments
      involving the type of samples relevant to the project at hand. The methods
      presented here have permitted large-scale DNA-based identification of persons
      missing from mass disasters and armed conflict.

PMID- 22139662
TI  - Interpretation guidelines for multilocus STR forensic profiles from low template
      DNA samples.
AB  - Low template (LT) DNA testing is a more sensitive method of PCR DNA typing which
      tests lower quantities of DNA compared to traditional PCR DNA protocols. Methods
      applied in this testing involve amplification or postamplification efforts to
      increase detection sensitivity. Establishing the interpretation rules of the
      results obtained is condition sine qua non for successful incorporation of this
      valuable technique into forensic casework. Here we describe a successfully
      optimized and validated approach to interpretation of LT-DNA samples.

PMID- 22139663
TI  - Interpretation guidelines for mixed-STR multilocus electrophoretic profiles.
AB  - The interpretation of multilocus STR profiling is a complex task that requires a
      high degree of expertise due to the high number of variables that can affect a
      biological and analytical process like this.The purpose of this chapter is to
      provide guidelines to categorize the mixtures using a discrete system and select
      those in the white area to produce a profile for reporting and/or comparing.

PMID- 22139664
TI  - Capillary electrophoresis analysis of a 9-plex STR assay for canine genotyping.
AB  - STR analysis of canine-derived biological evidence for the identification of
      individuals is becoming an important tool for forensic investigations. A protocol
      for the multiplex PCR amplification and capillary electrophoresis of nine
      autosomal STRs and two fixed-size markers for sex identification in dogs and
      wolves is described here. The selection of the loci included in the multiplex
      complies with the recommendations of the International Society for Forensic
      Genetics in regard to human DNA analysis. The protocol is optimized for automatic
      fragment size detection in an ABI platform.

PMID- 22139665
TI  - Capillary electrophoresis of DNA from Cannabis sativa for correlation of samples
      to geographic origin.
AB  - For routine genetic analysis of Cannabis sativa, two methods are currently in
      use, (a) AFLP; amplified fragment length polymorphism analysis and (b) STR; short
      tandem repeat analysis. The AFLP method used on capillary electrophoresis
      instrumentation is fully described in this chapter. AFLP analysis generates
      numerous nonspecific marker fragments for a complex DNA pattern and is available
      in kit format for quality assurance of reagents. This method is particularly
      useful when discerning the genetics of highly inbred plant species that may share
      much of the same DNA with only slight differences due to their common genetic
      background. AFLP analysis, however, is most effective on fresh or well-preserved
      plant specimens where the integrity of the DNA is high and the sample is a single
      source specimen (i.e., not a mixture of plants or different species).

PMID- 22139666
TI  - Capillary electrophoresis of multigene barcoding chloroplast markers for species
      identification of botanical trace evidence.
AB  - The analysis of nonhuman biological evidence both animal and botanical to find
      out the correct species of a sample comes as a great help to crime investigators.
      Particularly, forensic botany may be useful in many criminal and civil cases,
      e.g., for linking an individual to a crime scene or physical evidence to a
      geographic location, or tracking marijuana distribution patterns.Despite many
      molecular techniques for species identification so far applied, botanical
      evidences are still overlooked by forensic scientists due to the lack of
      reproducible and efficient protocols standardized across a wide range of
      different organisms and among different laboratories.Recently, the term "DNA
      barcoding" has been coined to describe the use of a short gene sequence from a
      standardized region of the genome as a molecular tool for species identification.
      DNA barcodes have been successfully applied to a number of animal groups and
      introduced in forensic science with the application of the mitochondrial gene
      COI. Building on this success, ongoing investigations have searched for the best
      barcode to apply to all land plants. Here we describe the basic protocol based on
      amplification and sequence analysis of barcoding markers for land plants
      considering the latest developments of Plant DNA barcoding Project. The aim of
      this chapter is to provide forensic scientists an accurate and reliable tool for
      assigning unidentified botanical specimens to the correct species as powerful
      mainstay in investigations, increasing the contributions from nonhuman DNA to
      forensics.

PMID- 22139667
TI  - Capillary electrophoresis of Big-Dye terminator sequencing reactions for human
      mtDNA Control Region haplotyping in the identification of human remains.
AB  - Cycle sequencing reaction with Big-Dye terminators provides the methodology to
      analyze mtDNA Control Region amplicons by means of capillary electrophoresis. DNA
      sequencing with ddNTPs or terminators was developed by (1). The progressive
      automation of the method by combining the use of fluorescent-dye terminators with
      cycle sequencing has made it possible to increase the sensibility and efficiency
      of the method and hence has allowed its introduction into the forensic field. PCR
      generated mitochondrial DNA products are the templates for sequencing reactions.
      Different set of primers can be used to generate amplicons with different sizes
      according to the quality and quantity of the DNA extract providing sequence data
      for different ranges inside the Control Region.

PMID- 22139668
TI  - Capillary electrophoresis of human mtDNA control region sequences from highly
      degraded samples using short mtDNA amplicons.
AB  - The forensic applications of mtDNA sequencing center primarily on samples that
      are either highly degraded or contain little or no nuclear DNA, since the testing
      of these sample types is often unsuccessful with more widely used nuclear STR
      profiling assays. In these cases, sequence data from the noncoding mtDNA control
      region are targeted due to its high variability. However, the ease of authentic
      DNA recovery and the strategy used for recovery depend strictly on the quality of
      the sample. In this chapter, we will cover mitochondrial DNA sequencing
      procedures for short mtDNA amplicons which range in size from 100 to 350 bp.
      Generally speaking, amplicons of this size are required only for the most
      degraded specimens, and the protocols described here have been specifically
      developed for recalcitrant human skeletal remains encountered during the course
      of a large-scale missing persons' identification effort. DNA templates from these
      types of specimens tend to exhibit various forms of intrastrand damage that, in
      turn, manifest as artifacts in the sequence data. Because these artifacts are not
      generally observed among sequence data from pristine templates, we address the
      particular data idiosyncrasies that warrant additional scrutiny. Although this
      chapter will primarily highlight this particular application, the basic
      experimental parameters and data considerations should easily extend to other
      applications and/or sample types. The protocols described here have been
      deliberately designed to produce raw sequence electropherograms and final mtDNA
      profiles that adhere to the strictest forensic guidelines in terms of overall
      data quality.

PMID- 22139669
TI  - Interpretation guidelines of mtDNA control region sequence electropherograms in
      forensic genetics.
AB  - Forensic mitochondrial DNA (mtDNA) analysis is a complementary technique to
      forensic nuclear DNA (nDNA) and trace evidence analysis. Its use has been
      accepted by the vast majority of courts of law around the world. However for the
      forensic community it is crucial to employ standardized methods and procedures to
      guaranty the quality of the results obtained in court. In this chapter, we
      describe the most important aspects regarding the interpretation and assessment
      of mtDNA analysis, and offer a simple guide which places particular emphasis on
      those aspects that can impact the final interpretation of the results. These
      include the criteria for authenticating a sequence excluding the contaminant
      origin, defining the quality of a sequence, editing procedure, alignment criteria
      for searching the databases, and the statistical evaluation of matches. It is not
      easy to establish a single guide to interpretation for mtDNA analysis; however,
      it is important to understand all variables that may in some way affect the final
      conclusion in the context of a forensic case. As a general rule, laboratories
      should be cautious before issuing the final conclusion of an mtDNA analysis, and
      consider any significant limitations regarding current understanding of specific
      aspects of the mtDNA molecule.

PMID- 22139670
TI  - Capillary electrophoresis of mtDNA cytochrome b gene sequences for animal species
      identification.
AB  - The identification of a biological species from an unknown material can be
      performed using a mitochondrial DNA locus. The cytochrome b (cyt b) gene is one
      of the most commonly used genetic loci, applied in both taxonomy and forensic
      science, for the purpose of species identification. The gene is 1,140 basepairs
      long in most vertebrates and shows little intraspecies variation, but sufficient
      interspecies variation. The gene is too long for typical PCR-based methods and,
      as many samples are degraded, only a section of the locus is used. DNA sequences
      at the start of the gene became the favored section for phylogenetics and species
      identification. The DNA sequences from any unknown sample from this part of the
      cyt b gene can be determined and compared to those on a DNA database to determine
      the most likely species from which the unknown sample originates. The process of
      DNA amplification, sequencing, sequence comparison, and identification form the
      basis of this chapter.

PMID- 22139671
TI  - Sequence analysis of the canine mitochondrial DNA control region from shed hair
      samples in criminal investigations.
AB  - In recent years, evidence from domestic dogs has increasingly been analyzed by
      forensic DNA testing. Especially, canine hairs have proved most suitable and
      practical due to the high rate of hair transfer occurring between dogs and
      humans. Starting with the description of a contamination-free sample handling
      procedure, we give a detailed workflow for sequencing hypervariable segments
      (HVS) of the mtDNA control region from canine evidence. After the hair material
      is lysed and the DNA extracted by Phenol/Chloroform, the amplification and
      sequencing strategy comprises the HVS I and II of the canine control region and
      is optimized for DNA of medium-to-low quality and quantity. The sequencing
      procedure is based on the Sanger Big-dye deoxy-terminator method and the
      separation of the sequencing reaction products is performed on a conventional
      multicolor fluorescence detection capillary electrophoresis platform. Finally,
      software-aided base calling and sequence interpretation are addressed
      exemplarily.

PMID- 22139672
TI  - Integrated sample cleanup and microchip capillary array electrophoresis for high
      performance forensic STR profiling.
AB  - Microfluidics has the potential to significantly improve the speed, throughput,
      and cost performance of electrophoretic short tandem repeat (STR) analysis by
      translating the process into a miniaturized and integrated format. Current STR
      analysis bypasses the post-PCR sample cleanup step in order to save time and
      cost, resulting in poor injection efficiency, bias against larger loci, and
      delicate injection timing controls. Here we describe the operation of an
      integrated high-throughput sample cleanup and capillary array electrophoresis
      microsystem that employs a streptavidin capture gel chemistry coupled to a simple
      direct-injection geometry for simultaneously analyzing 12 STR samples in less
      than 30 min with >10-fold improved sensitivity.

PMID- 22139673
TI  - Microchip capillary electrophoresis protocol to evaluate quality and quantity of
      mtDNA amplified fragments for DNA sequencing in forensic genetics.
AB  - Here, we describe a microcapillary electrophoresis technique with application to
      the quantitative analysis of mtDNA hypervariable regions HVR1, HVR2, and HVR3 PCR
      amplicons previous to sequence analysis, which yields several important
      advantages compared to traditional separation and detection methods. Based on
      laser-induced fluorescence (LIF) detection, and performed in a microchip, this
      analysis system enables the handling of very small volumes via microchannels
      etched in the chip. Moreover it is faster than traditional methods; chip priming
      and sample loading are the only manual interventions, as the rest of the process
      is fully automated by software control: injection, electrophoretic separation,
      detection of the fluorescent signal, and calculation of both quantity and size.
      MtDNA amplicons are separated in microchannels with an effective length of 15 mm
      and detected by means of the fluorescence displayed by an intercalated dye. A
      software records the fluorescence and entails the data into size and
      concentration through the use of two internal standards and an external ladder of
      11 fragments. The effectiveness of this procedure has been illustrated with a
      validation experiment carried out in our laboratory, in order to assess the
      detection limit of mtDNA sequencing by determining the minimal amount of PCR
      amplicon needed to edit a reproducible and high quality mtDNA sequence from
      complementary sequence data obtained using forward and reverse primers.

PMID- 22139674
TI  - Microchip Capillary electrophoresis of multi-locus VNTR analysis for genotyping
      of Bacillus anthracis and Yersinia pestis in microbial forensic cases.
AB  - Bacillus anthracis and Yersinia pestis are etiological agents of anthrax and
      plague respectively, and are also considered among the most feared potential
      bioterrorism agents. These microorganisms show intraspecies genome homogeneity,
      making strains differentiation difficult, while strains identification and
      comparison with known genotypes may be crucial for naturally occurring outbreaks
      vs. bioterrorist events discrimination.Here an MLVA application for B. anthracis
      and Y. pestis strains differentiation is described on Microchip Capillary
      electrophoresis apparatus. The platform is a candidate for on-site MLVA
      genotyping of biothreat agents as well as other bacterial pathogens. This
      microfluidics-based electrophoresis analysis system represents an alternative to
      the more expensive and demanding capillary electrophoresis methods, and to the
      less expensive but more time-consuming standard agarose gel approach.

PMID- 22139675
TI  - Amination with Pd-NHC complexes: rate and computational studies involving
      substituted aniline substrates.
AB  - The amination of aryl chlorides with various aniline derivatives using the N
      heterocyclic carbene-based Pd complexes Pd-PEPPSI-IPr and Pd-PEPPSI-IPent
      (PEPPSI=pyridine, enhanced precatalyst, preparation, stabilization, and
      initiation; IPr=diisopropylphenylimidazolium derivative; IPent=
      diisopentylphenylimidazolium derivative) has been studied. Rate studies have
      shown a reliance on the aryl chloride to be electron poor, although oxidative
      addition is not rate limiting. Anilines couple best when they are electron rich,
      which would seem to discount deprotonation of the intermediate metal ammonium
      complex as being rate limiting in favour of reductive elimination. In previous
      studies with secondary amines using PEPPSI complexes, deprotonation was proposed
      to be the slow step in the cycle. These experimental findings relating to
      mechanism were corroborated by computation. Pd-PEPPSI-IPr and the more hindered
      Pd-PEPPSI-IPent catalysts were used to couple deactivated aryl chlorides with
      electron poor anilines; while the IPr catalysis was sluggish, the IPent catalyst
      performed extremely well, again showing the high reactivity of this broadly
      useful catalyst.

PMID- 22139676
TI  - Interactions between methylmercury and selenomethionine injected into mallard
      eggs.
AB  - Methylmercury chloride and seleno-L-methionine were injected separately or in
      combinations into mallard eggs (Anas platyrhynchos), and embryo mortality and
      teratogenic effects (deformities) were modeled using a logistic regression model.
      Methylmercury was injected at doses that resulted in concentrations of 0, 0.2,
      0.4, 0.8, and 1.6 ug/g Hg in the egg on a wet weight basis and selenomethionine
      at doses that resulted in concentrations of 0, 0.1, 0.2, 0.4, and 0.6 ug/g Se in
      the egg, also on a wet weight basis. When selenomethionine and methylmercury were
      injected separately, hatching probability decreased in both cases. However, when
      methylmercury was injected at 1.6 ug/g in combination with selenomethionine at
      0.2 ug/g, the presence of the methylmercury resulted in less embryo mortality
      than had been seen with 0.2 ug/g Se by itself, but it increased the number of
      deformed embryos and hatchlings. Selenomethionine appeared to be more embryotoxic
      than equivalent doses of methylmercury when injected into eggs, and both injected
      methylmercury and selenomethionine were more toxic to mallard embryos than when
      deposited naturally in the egg by the mother. The underlying mechanisms behind
      the interactions between methylmercury and selenomethionine and why methylmercury
      appeared to improve hatching probability of Se-dosed eggs yet increased
      deformities when the two compounds were combined are unclear. These findings
      warrant further studies to understand these mechanisms in both laboratory and
      field settings.

PMID- 22139677
TI  - The psychological impact of deployment on OEF/OIF healthcare providers.
AB  - The psychological impact of military experience on healthcare providers has
      received little attention to date. The 2005 Department of Defense Survey of
      Health Related Behaviors Among Active Duty Personnel was used as a secondary data
      source, and deployed healthcare officers and healthcare specialists were
      identified and compared to deployed non-healthcare officers and enlisted
      personnel: 6,116 respondents were surveyed. Findings revealed clinically
      significant psychological distress among deployed military healthcare provider
      respondents including posttraumatic stress symptoms, depression, anxiety, and
      adverse psychosocial impact, more prominent in the deployed healthcare specialist
      group. Based upon findings, possible factors for resilience and increased risk,
      as well as potential intervention needs in this healthcare provider group of
      service members are offered. Implications for future prospective studies are
      suggested.

PMID- 22139678
TI  - Application of drug metabolism and pharmacokinetics for new drug development.

PMID- 22139679
TI  - SHINBARO, a new herbal medicine with multifunctional mechanism for joint disease:
      first therapeutic application for the treatment of osteoarthritis.
AB  - SHINBARO is a purified extract from a mixture of 6 oriental herbs (Ledebouriellae
      Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen,
      and Eucommiae Cortex) that have been used as a traditional medicine for treatment
      of several inflammatory diseases and bone disorders. We determined
      antiinflammatory and antinociceptive activities of SHINBARO in adjuvant-induced
      (osteo)arthritis in rats. This potential anti-(osteo)arthritic property of
      SHINBARO can be due to the downregulation of inflammatory mediators such as iNOS,
      COX-2, and TNF-alpha, the increase of pain threshold in the peripheral system,
      the activation of alkaline phosphatase in osteoblasts, the suppression of
      proteoglycan degradation, and the inhibition of MMP-2 and MMP-9 activities as
      demonstrated by in vitro and in vivo experimental studies. We confirmed that
      SHINBARO is as effective as celecoxib, a selective COX-2 inhibitor, but it has
      the better safety profile in clinical trials. Finally, SHINBARO was approved as a
      New Herbal Medicine for treatment of osteoarthritis by Korean FDA on January
      25(th), 2011.

PMID- 22139680
TI  - Approaches for predicting human pharmacokinetics using interspecies
      pharmacokinetic scaling.
AB  - Reliably predicting pharmacokinetic behavior in humans from preclinical data is
      an important aspect of drug development. The most widely used technique in this
      regard is allometric scaling. In this review, various approaches developed for
      predicting pharmacokinetic parameters in humans using interspecies scaling are
      introduced and discussed. Methods to predict plasma concentration-time profiles
      in humans after intravenous and oral administration are also reviewed. The
      reliable prediction of human pharmacokinetics with regard to investigational
      drugs is aimed, ultimately, at selecting the first in-human dose with which to
      begin clinical studies. Approaches for the selection of the first in-human dose
      are also reviewed. Although there have been many trials to compare and optimize
      interspecies scaling methods, no firm conclusions have been reached. Because
      interspecies scaling methods are still highly empirical, further effort is needed
      to improve the reliability of predicting human pharmacokinetics by interspecies
      scaling.

PMID- 22139681
TI  - Microdosing studies using accelerated mass spectrometry as exploratory
      investigational new drug trials.
AB  - Innovative attempts have been made to overcome nonproductivity and high
      expenditure in the clinical stages of new drug development. Microdosing studies
      using subpharmacological doses provide early insight into the body's disposition
      toward candidate compounds, and are innovative exploratory trials that can
      promote productivity in drug development. Highly sensitive analytical technology
      is crucial in microdosing studies that employ qualitative and quantitative assays
      of target materials in humans. Accelerator mass spectrometry (AMS) has
      facilitated the adoption of a human microdosing study in the early phase of
      clinical drug development. Results derived from AMS microdosing studies using
      labeled compounds can provide various types of information for candidate
      selection, including pharmacokinetic characteristics and metabolic profiles of
      candidate compounds. The applicability of microdosing studies is currently
      expanding into absolute bioavailability and mass balance studies. Although it
      remains uncertain whether microdosing adequately predicts the pharmacokinetics of
      therapeutic doses, further development of microdosing studies using AMS may
      benefit the field of new drug development and could pose a new challenge to
      researchers. The use of advanced technology in candidate selection will
      contribute to improved productivity and competitiveness in pharmaceutical
      research and development. The introduction of microdosing studies using AMS in
      Korea will present a newly applicable method for innovative clinical trials and
      contribute to development potential in global competition.

PMID- 22139682
TI  - Polymorphic metabolism by functional alterations of human cytochrome P450
      enzymes.
AB  - The study of cytochrome P450 pharmacogenomics is of particular interest because
      of its promise in the development of rational means to optimize drug therapy with
      respect to patient's genotype to ensure maximum efficacy with minimal adverse
      effects. Drug metabolizing P450 enzymes are polymorphic and are the main phase I
      enzymes responsible for the metabolism of clinical drugs. Therefore,
      polymorphisms in the P450s have the most impact on the fate of clinical drugs in
      phase I metabolism since almost 80% of drugs in use today are metabolized by
      these enzymes. Predictive genotyping for P450 enzymes for a more effective
      therapy will be routine for specific drugs in the future. In this review, we
      discuss the current knowledge of polymorphic metabolism by functional alterations
      in nonsynonymous SNPs of P450 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, and 3A4 enzymes.

PMID- 22139683
TI  - Interplay of pharmacogenetic variations in ABCB1 transporters and cytochrome P450
      enzymes.
AB  - Interindividual variability in oral drug efficacy and toxicity is commonly
      observed in all therapeutic areas. Importantly, interindividual variability in
      drug uptake and metabolism can result in poor drug response, adverse drug
      reactions, or unfavorable drug-drug interaction. One of the common causes of
      individual variations in drug response is genetic variation of drug transporters
      and metabolizing enzymes. Pharmacogenetics are rapidly elucidating the inherited
      nature of these differences in drug disposition and effects, thereby providing a
      stronger scientific basis for optimizing drug therapy on the basis of each
      patient's genetic constitution. Knowledge of the genotype-phenotype correlation
      and frequency distribution of functional single nucleotide polymorphisms may be a
      valuable tool for individualizing drug therapy. This information can also be
      useful for explaining inter-individual and inter-ethnic variations in drug
      response and/or adverse effects. In this review, we focus on the interplay
      between efflux transporter (ATP-binding cassette, sub-family B (MDR/TAP), member
      1/ABCB1) and cytochrome P450s according to genetic polymorphism.

PMID- 22139684
TI  - Evaluation of metabolism-mediated herb-drug interactions.
AB  - As the use of herbal medicines increases, the public health consequences of drug
      herb interactions are becoming more significant. Herbal medicines share the same
      drug metabolizing enzymes and drug transporters, including cytochrome P450
      enzymes (CYPs), glucuronosyltransferases (UGTs), and P-glycoprotein, with several
      clinically important drugs. Interactions of several commonly used herbal
      medicines, such as Ginko biloba, milk thistle, and St. John's wort, with
      therapeutic drugs including warfarin, midazolam, alprazolam, indinavir,
      saquinavir, digoxin, nifedipine, cyclosporine, tacrolimus, irinotecan, and
      imatinib in humans have been reported. Many of these drugs have very narrow
      therapeutic indices. As the herb-drug interactions can significantly alter
      pharmacokinetic and pharmacodynamic properties of administered drugs, the drugs
      interacting with herbal medicines should be identified by appropriate in vitro
      and in vivo methods. A good understanding of the mechanisms of herb-drug
      interactions is also essential for assessing and minimizing clinical risks. In
      vitro methods are useful for providing mechanistic information and evaluating
      multiple components in herbal medicines. This review describes major factors
      affecting the metabolism of herbal medicines, mechanisms of herb-drug
      interactions mediated by CYPs and UGTs, and several in vitro methods to assess
      the herb-drug interactions. Finally, drug interactions of Ginkgo biloba and St.
      John's wort, as representative herbal medicines, are described.

PMID- 22139685
TI  - Herb-drug interactions: focus on metabolic enzymes and transporters.
AB  - As the uses of herbal medicines from traditional natural products are increased,
      the need for pharmacokinetic studies and relevant data are also increased for
      safe pharmacotherapy. The market entry for the traditional herbal medicine is
      easier compared with that for synthetic drugs because of a lower regulatory
      barrier. Thus, the exact mechanisms for the absorption, distribution, metabolism
      and excretion of active components in herbal medicines and the potential herb
      drug interactions are not always fully understood. Recently, there has been an
      increasing interest in pharmacokinetic studies of herbal remedies and relevant
      data of commonly used herbal remedies are accumulating in this field. In this
      review, the effects of nine botanicals (ginkgo, green tea, grapes, licorice, saw
      palmetto, garlic milk thistle, ginseng and St. John's wort) on metabolic enzymes
      and transporters affecting absorption and disposition of herbal products are
      summarized. The source of samples (extracts and individual components), the
      species (human and animal) and in vivo and in vitro systems were separately
      reviewed for a better understanding of herb-drug interactions.

PMID- 22139686
TI  - Role of transporters in drug interactions.
AB  - Over the past few decades, a tremendous amount of work has been done on the
      molecular characterization of transport proteins in animals and humans, leading
      to a better understanding of the physiological roles of a number of transport
      proteins. Furthermore, there is increasing preclinical and clinical evidence to
      support the importance of transport proteins in the pharmacokinetics and
      toxicokinetics of a wide variety of structurally diverse drugs. As a consequence,
      the degree of expression and functionality of transport proteins may directly
      affect the therapeutic effectiveness, safety and target specificity of drugs.
      Recently, there has also been increased awareness about potential drug-drug, drug
      herb and drug-food interactions involving transporters. Traditionally, a change
      in metabolic clearance of a drug, particularly via cytochrome P450-mediated
      metabolism, has been considered the cause of many clinically important drug
      interactions. However, increasing evidence suggests that some drug interactions
      result from changes in the activity and/or expression of drug transporters.
      Accordingly, assessment of the clinical relevance of transporter-mediated drug
      interactions has become a regulatory issue during the drug approval process and
      also the evaluation of drug interaction potential has become an integral part of
      risk assessment during drug development processes. Therefore, this review will
      highlight the role of some selected drug transporters in drug interactions, as
      well as their clinical implication.

PMID- 22139687
TI  - Assessment of reactive metabolites in drug-induced liver injury.
AB  - The aim of the current review is to summarize present methods used for the
      determination of reactive metabolites, which can predict drug-induced liver
      injury (DILI) in drug discovery and development. DILI is one of the most frequent
      reasons for the withdrawal of an approved drug from the market, and it accounts
      for up to 50% of acute liver failure cases. This review is structured into three
      sections. The first section is a general overview of the relationship between
      drug metabolism and liver injury. The second section introduces in vitro methods
      for the assessment of reactive metabolites for drug discovery and development. In
      the third section, limitations and future directions for the development of
      methods for predicting DILI are described.

PMID- 22139688
TI  - Designing micro- and nano-particles for treating rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, destructive autoimmune disease that can
      cause disability and have a negative socioeconomic impact. Despite significant
      advances in therapeutic options, limitations on the routes of administration and
      the requirement for frequent and long-term dosing often lead to systemic adverse
      effects and patient non-compliance. Micro and nanoparticle systems that
      selectively deliver drugs to inflamed synovium have the potential to improve drug
      efficacy while leaving extrasynovial tissues unaffected. This review summarizes
      key design parameters of RA-targeted drug carriers and discusses design
      considerations for improving RA therapies.

PMID- 22139689
TI  - Preparation and investigation of Ulex europaeus agglutinin I-conjugated liposomes
      as potential oral vaccine carriers.
AB  - We prepared and optimized Ulex europaeus agglutinin I (UEAI)-modified Bovine
      serum albumin (BSA)-encapsulating liposomes (UEAI-LIP) as oral vaccine carriers
      and examined the feasibility of inducing systemic and mucosal immune responses by
      oral administration of UEAILIP. The prepared systems were characterized in vitro
      for their average size, zeta potential, encapsulation efficiency (EE%) and
      conjugation efficiency (CE%). In vitro release studies indicated that the
      presence of UEAI around the optimized liposomes was able to prevent a burst
      release of loaded BSA and provide sustained release of the encapsulated protein.
      In vivo immune-stimulating results in KM mice showed that BSA given
      intramuscularly generated systemic response only but both systemic and mucosal
      immune responses could be induced simultaneously in the groups in which BSA
      loaded liposomes (LIP) and UEAI-LIP were administered intragastrically.
      Furthermore, the modification of UEAI on the surface of liposomes could further
      enhance the IgA and IgG levels obviously. In conclusion, this study demonstrated
      the high potential of lectin-modified liposomes containing the antigen as
      carriers for oral vaccine.

PMID- 22139690
TI  - Preparation and characterization of emulsified solid dispersions containing
      docetaxel.
AB  - An emulsified solid dispersion of docetaxel was prepared and characterized in
      vitro. In contrast to conventional solid dispersions, emulsifying pharmaceutical
      excipients and hydroxypropyl methylcellulose (HPMC) as a supersaturation promoter
      were introduced into the PEG6000-based solid dispersion to further improve its
      solubilizing capability. The solubility, dissolution in vitro and stability of
      the prepared emulsified solid dispersions were studied taking into consideration
      of the effects of different emulsifying excipients, preparation methods and the
      media. Results of the emulsified solid dispersion of docetaxel showed that the
      solubility and dissolution at 2 h were 34.2- and 12.7-fold higher than the crude
      powder. The type of emulsifying excipient used had a significant influence on the
      dissolution of the emulsified solid dispersion. The dissolution of the emulsified
      solid dispersion prepared by the solvent-melting method or the solvent method was
      higher than the melting method. There were no apparent differences among the
      dissolution media utilized. The status of the drug in the emulsified solid
      dispersion was observed in an amorphous or a molecular dispersion state by
      differential thermal analysis and powder Xray diffraction. In conclusion, the
      incorporation of emulsifying pharmaceutical excipients and HPMC with polymers
      into a solid dispersion could be a new and useful tool to greatly increase the
      solubility and dissolution of poorly water-soluble drugs.

PMID- 22139691
TI  - Controlled release chitosan microspheres of mirtazapine: in vitro and in vivo
      evaluation.
AB  - The purpose of the study was to formulate and evaluate controlled release
      chitosan microspheres of mirtazapine (MTZ) to improve the bioavailability by
      altering the pharmacokinetic profiles of the drug. Chitosan microspheres were
      prepared to prolong the release of the drug into the systemic circulation.
      Microspheres were prepared by a single water in oil (w/o) emulsion technique
      varying the chitosan/drug ratio, stirring speed and concentration of the
      crosslinking agent (glutaraldehyde). Drug-polymer compatibility studies were
      carried out using fourier transform infrared spectroscopy (FT-IR) and
      differential scanning calorimetry (DSC). The microspheres were evaluated for
      encapsulation efficiency, particle size, surface morphology, swelling index, in
      vitro release, as well as erosion and in vivo studies in rats. The FT-IR and DSC
      studies revealed no interaction between drug and polymer. The encapsulation
      efficiency of different formulation varied from 53 +/- 1.2% to 78 +/- 1.5%. The
      mean particle size of the optimized formulation F-14 was 106.4 +/- 0.5 MUm.
      Surface morphology revealed that chitosan microspheres were discrete and
      spherical in shape with a porous surface. The release of MTZ from chitosan
      microspheres was rapid up to 4 h, and then it was continuously and slowly
      released up to 48 h. Optimized formulation (F-14) was found to be stable under
      accelerated storage conditions based on International Conference on Harmonisation
      guidelines. Pharmacokinetic studies revealed that the optimized formulation
      showed significant increases in systemic exposure (AUC = 177.70 +/- 7.39
      MUg.h/mL), half-life (4.72 +/- 0.46 h) and reduced clearance (0.009 +/- 0.0001
      L/h) compared to pure drug administration. Hence, the present study demonstrates
      that controlled release formulation of MTZ microspheres using chitosan can
      improve pharmacokinetic profiles of MTZ.

PMID- 22139692
TI  - Preparation of lovastatin matrix sustained-release pellets by extrusion
      spheronization combined with microcrystal dispersion technique.
AB  - The poorly water-soluble drug lovastatin (LVA) is an inhibitor of 3-hydroxy-3
      methylglutarylcoenzyme A reductase and has a slow dissolution rate. In this
      study, a microcrystal dispersion (MCD) technique was used in the preparation of
      LVA to increase its dissolution rate and then combining with an extrusion
      spheronization method, microcrystalline cellulose (MCC) matrix sustained-release
      pellets containing LVA-MCD were developed and characterized in vitro.
      Photomicrographs indicated that LVA-MCD existed as fine crystals, of which the
      mean particle size was reduced from 65.75 MUm to 3.97 MUm and the dried LVA-MCD
      powders released completely within 2 hours. SEM results during the release
      process showed that pellets possessed a matrix structure and after the
      dissolution test, this matrix structure became loose and porous. The release of
      LVA was fast and complete, and accumulated release by the optimal formulation
      was: 0.5 h (20.23 +/- 3.40%), 2 h (56.87 +/- 2.85%), 4 h (78.71 +/- 3.42%), and 8
      h (96.81 +/- 3.30%). The 3 months accelerating test at 40 degrees C and 75% RH
      demonstrated that drug release of pellets was not changed and drug degradation
      was less than 1%. Thus, a novel MCD process with MCC matrix was feasible and
      effective to get complete release without a lag time for the poorly water soluble
      drug, LVA, with high stability.

PMID- 22139693
TI  - Effects of Pluronic F68 and Labrasol on the intestinal absorption and
      pharmacokinetics of rifampicin in rats.
AB  - The aim of this study was to investigate the effects of Pluronic F68 and Labrasol
      on the intestinal absorption and pharmacokinetics of rifampicin. Intestinal
      permeability of rifampicin with or without excipients was evaluated by an in situ
      single-pass perfusion method. A high-performance liquid chromatographic method
      was applied to study the pharmacokinetics of rifampicin with or without
      excipients. Labrasol or Pluronic F68 (0.1% and 0.05%, v/v), co-perfused with
      rifampicin (60 MUg/mL), significantly increased in situ permeability. Similarly,
      verapamil (a typical P-gp inhibitor) also increased in situ permeability, but to
      a lesser extent. In vivo, the oral administration of rifampicin with or without
      Pluronic F68, Labrasol or verapamil resulted in statistically significant effect
      on t(1/2) (4.83 to 7.75, 6.42 and 7.46 h) and total body clearance (0.46 to 0.26,
      0.28, 0.24 L/h/kg). In addition, Pluronic F68, Labrasol and verapamil produced
      minor changes in AUC(0-t), which improved 1.55-, 1.54-, and 1.73-fold in
      comparison to control group, respectively. These results showed that Labrasol and
      Pluronic F68 might inhibit the function of P-gp in the intestine, thereby
      increasing intestinal absorption and changing the pharmacokinetic parameters of
      rifampicin. Therefore, excipient selection is an important factor to consider in
      rational formulation design.

PMID- 22139694
TI  - Formulation and in vivo evaluation of ondansetron orally disintegrating tablets
      using different superdisintegrants.
AB  - The aim of this study was to formulate cost effective taste-masked orally
      disintegrating tablets of ondansetron, a bitter drug using different
      superdisintegrants by a wet granulation technique. Microcrystalline cellulose
      (Avicel) as a diluent and disintegrant in addition to aspartame as a sweetener
      were used in all formulations. The prepared tablets were evaluated for weight
      variation, thickness, hardness, friability, drug content, water content, in vitro
      disintegration time and in vitro drug release. The tablets' hardness was
      maintained in the range of 2-3 kg and friability was <1% for all batches. All
      tablet formulations disintegrated rapidly in vitro within 5.83 to 33.0 sec. The
      optimized formulation containing 15% Polyplasdone XL-10 released more than 90% of
      drug within 5 min and the release was comparable to that of a commercial product.
      In human volunteers, optimized formulation was found to have a pleasant taste and
      mouth feel and they disintegrated in the oral cavity within 12 sec. The stability
      results were also satisfactory. A pharmacokinetic study with the optimized
      formulation was performed in comparison with a reference (Zofer MD 8(r)) and they
      were found to be bioequivalent. In conclusion, a cost effective ondansetron
      orally disintegrating tablet was successfully prepared with acceptable hardness,
      desirable taste and rapid disintegration in the oral cavity.

PMID- 22139695
TI  - Effect of diallyl trisulfide on the pharmacokinetics of dipyridamole in rats.
AB  - This study was aimed to evaluate the effect of diallyl trisulfide (DATS), a major
      component derived from garlic used to inhibit platelet thromboxane formation, on
      the pharmacokinetics of dipyridamole. Pharmacokinetic parameters of dipyridamole
      were determined in rats following intragastric (80 mg/kg suspension or 40 mg/kg
      solution) or intravenous (3 mg/kg) administration of dipyridamole with
      coadministration (20 mg/kg) and long-term pretreatment of DATS (10 or 20
      mg/kg/day for 15 consecutive days). In addition, everted gut sac models were used
      to assess transepithelial transport of dipyridamole and the effect of DATS on the
      intestinal absorption of dipyridamole. After coadministration and long-term
      pretreatment of DATS, significantly lower Cmax and AUC(0-24 h) were observed for
      intragastric administration of dipyridamole, whereas little change was noted
      after intravenous dipyridamole administration. After adding DATS (10 and 50
      MUg/mL) in the everted gut sacs, absorption of dipyridamole was remarkably
      decreased in the ileum and jejunum (p < 0.01). In conclusion, DATS reduced the
      oral exposure of dipyridamole in rats likely by the modification of the
      dissolution rate and intestinal absorption of dipyridamole, indicating that
      combined use of DATS or DATS-containing supplements with dipyridamole may require
      caution as low plasma concentrations of dipyridamole may lead to a subtherapeutic
      effect of this agent.

PMID- 22139696
TI  - Effects of baicalein on the pharmacokinetics of tamoxifen and its main
      metabolite, 4-hydroxytamoxifen, in rats: possible role of cytochrome P450 3A4 and
      P-glycoprotein inhibition by baicalein.
AB  - The purpose of this study was to investigate the effects of baicalein on the
      pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen, in
      rats. Tamoxifen and baicalein interact with cytochrome P450 (CYP) enzymes and P
      glycoprotein (P-gp), and the increase in the use of health supplements may result
      in baicalein being taken concomitantly with tamoxifen as a combination therapy to
      treat orprevent cancer diseases. Pharmacokinetic parameters of tamoxifen and 4
      hydroxytamoxifen were determined in rats after an oral administration of
      tamoxifen (10 mg/kg) to rats in the presence and absence of baicalein (0.5, 3,
      and 10 mg/kg). Compared to the oral control group (given tamoxifen alone), the
      area under the plasma concentration-time curve and the peak plasma concentration
      of tamoxifen were significantly increased by 47.6-89.1% and 54.8-100.0%,
      respectively. The total body clearance was significantly decreased (3 and 10
      mg/kg) by baicalein. Consequently, the absolute bioavailability of tamoxifen in
      the presence of baicalein (3 and 10 mg/kg) was significantly increased by 47.5
      89.1% compared with the oral control group (20.2%). The metabolite-parent AUC
      ratio of tamoxifen was significantly reduced, implying that the formation of 4
      hydroxytamoxifen was considerably affected by baicalein. Baicalein enhanced the
      oral bioavailability of tamoxifen, which may be mainly attributable to inhibition
      of the CYP3A4-mediated metabolism of tamoxifen in the small intestine and/or in
      the liver, and inhibition of the P-gp efflux pump in the small intestine and/or
      reduction of total body clearance by baicalein.

PMID- 22139697
TI  - Pharmacokinetics of carbamazepine polymorphs and dihydrate in rats, related to
      dogs and humans.
AB  - Species differences in the oral pharmacokinetics and absolute bioavailability (F
      ( abs )) of carbamazepine polymorphs (form I and form III) and dihydrate were
      studied. The pharmacokinetics of each form was investigated in rats following a
      single oral/intravenous administration of 10 mg/kg and an oral dose of 80 mg/kg,
      which were compared with the published data obtained from dogs and humans. No
      significant differences were found in their C (max), T (max), AUC(0-infinity) and
      F ( abs ) among the forms at the low dose. However, significant differences were
      observed at the high dose. The Fabs of each form was markedly reduced with
      increasing of doses in species (e.g. F ( abs ) in rats ranged from > 82% to 38.4%
      56.0%). At a comparable dose, the C (max), and AUC(0-infinity) of rats and humans
      were about 3-10 times higher than in dogs. The absorption rate of form III in
      rats exhibited a similar trend to that in humans, and was far higher in dogs. A
      multi-peak phenomenon in plasma curves was observed in rats and humans, but not
      in dogs. In conclusion, rats appear to be a better predictor of carbamazepine
      polymorphs absorbed in humans, and form III may be more suitable as a
      pharmaceutical crystal.

PMID- 22139698
TI  - Determination of loperamide in mdr1a/1b knock-out mouse brain tissue using matrix
      assisted laser desorption/ionization mass spectrometry and comparison with
      quantitative electrospray-triple quadrupole mass spectrometry analysis.
AB  - Recently matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS)
      imaging has been used to analyze small molecule pharmaceutical compounds directly
      on tissue sections to determine spatial distribution within target tissue and
      organs. The data presented to date usually indicate relative amounts of drug
      within the tissue. The determination of absolute amounts is still done using
      tissue homogenization followed by traditional liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). In this study, the quantitative determination of
      loperamide, an antidiarrheal agent and a P-glycoprotein substrate, in mdr1a/1b (
      /-) mouse brain tissue sections using MALDI MS on a quadrupole time-of-flight
      mass spectrometry is described. 5 mg/mL alpha-cyano-4-hydroxycinnamic acid in 50%
      acetonitrile with 0.1% trifluoroacetic acid and 0.5 MUM reserpine was used as the
      MALDI matrix. The calibration curve constructed by the peak intensities of
      standard samples from MALDI MS was linear from 0.025 to 0.5 MUM with r2 = 0.9989.
      The accuracy of calibration curve standards was 78.3-105.9% and the percent
      deviation was less than 25%. Comparison between direct MALDI tissue analysis and
      conventional tissue analysis using homogenization followed by electrospray LC
      MS/MS was also explored.

PMID- 22139700
TI  - The risks and benefits of transseptal endocardial pacing.
AB  - PURPOSE OF REVIEW: Transseptal endocardial left-ventricular pacing has a number
      of potential advantages over left-ventricular epicardial pacing from the coronary
      sinus, for implantation of cardiac resynchronization therapy (CRT) devices. In
      this study we review the risks and potential benefits. RECENT FINDINGS: Permanent
      transseptal endocardial pacing has been shown to be clinically feasible.
      Different methods have been described, including a superior, inferior or mixed
      approach. Endocardial pacing has a number of potential advantages over
      conventional left-ventricular pacing from the coronary sinus. It may be possible
      to achieve more effective CRT through optimizing the left-ventricular lead
      position, which is possible because of the greater choice of stimulation site.
      Endocardial rather than epicardial stimulation may result in more rapid
      ventricular activation and may be less arrhythmogenic. Disadvantages of this
      approach include the risk of thromboembolism and the potential for interaction
      with the mitral valve. SUMMARY: Transseptal endocardial left-ventricular pacing
      shows promise for use in cardiac resynchronization therapy. The safety and
      effectiveness of this technique should now be tested in larger clinical trials.

PMID- 22139699
TI  - The effects of PLGA microparticles on intestinal absorption of p-glycoprotein
      substrate using the everted rat intestinal sac model.
AB  - In addition to the effects of physical processes (solubility, tissue
      permeability, and formulation factors), p-glycoprotein (P-gp) efflux across the
      apical membrane of enterocytes can affect the rate and amount of compound
      diffusing across the basolateral membrane of the intestine and entering the blood
      stream. The first objective was the evaluation of a possible role of intestinal P
      gp in the kinetic absorption of a model drug: furosemide. To achieve this goal,
      two series of transport experiments, apical to basolateral (A -> B) and
      basolateral to apical (B -> A) with and without verapamil -a known P-gp inhibitor
      were performed. The second objective was to evaluate whether encapsulation into
      polymeric microparticles might improve the oral absorption of a poorly permeable
      drug. Thus, spherical poly lactic-glycolic acid (PLGA) microparticles of
      furosemide were designed, and the concentration of transported drug was evaluated
      using an in situ everted rat gut sac model. The results indicated that verapamil
      at various drug concentrations (5-100 MUg/mL) significantly decreased the B -> A
      (2-3 fold) and increased the A -> B (1.5-2 fold) permeability of furosemide,
      which showed that this drug could be a P-gp substrate. We found that
      encapsulation of furosemide in PLGA microparticles can markedly increase (2-4
      fold) intestinal absorption of drug even higher than verapamil does. We conclude
      that biodegradable microparticles are a promising strategy to increase the
      bioavailability of drugs and have advantages compared to P-gp inhibitors with
      pharmacological and severe side effects at doses required for efflux pump
      inhibition.

PMID- 22139701
TI  - Sudden cardiac death in athletes:  what is the role of screening?
AB  - PURPOSE OF REVIEW: To briefly review the field of sudden cardiac death (SCD) in
      the athlete and the impact of preparticipation screening on identification of at
      risk cardiovascular disorders and mortality reduction. RECENT FINDINGS:
      Competitive sports activity is associated with an increase in the risk of SCD in
      susceptible adolescents and young adults with clinically silent cardiovascular
      disorders. Screening including 12-lead electrocardiogram (ECG) has been
      demonstrated to allow identification of athletes affected by malignant heart
      muscle diseases at a presymptomatic stage and lead to substantial reduction of
      the risk of SCD during sports. The use of modern criteria for interpretation of
      the ECG in the athlete significantly improves the screening accuracy by reducing
      the false-positive rate (increased specificity), with the important requisite of
      maintaining the ability for detection of life-threatening heart diseases
      (preserved sensitivity). Screening including ECG has a more favourable cost
      benefit ratio than that based on history and physical examination alone, with
      cost estimates per year of life saved below the threshold to consider a health
      intervention as cost-effective. Screening with exercise testing middle
      aged/senior athletes engaged in leisure sports activity is likely to be cost
      effective in older patients with coronary risk factors, while it is not justified
      in low-risk subgroups. SUMMARY: Preparticipation screening is a life-saving and
      cost-effective strategy in young athletes in whom SCD is mostly caused by ECG
      detectable heart muscle diseases.

PMID- 22139703
TI  - An expanding role for primary care providers in the treatment of hepatitis C
      virus infection in the community.

PMID- 22139702
TI  - Neural mechanisms of atrial fibrillation.
AB  - PURPOSE OF REVIEW: The autonomic nerve system is a potentially potent modulator
      of the initiation and perpetuation of atrial fibrillation. This review will
      briefly summarize the neural mechanisms of atrial fibrillation. RECENT FINDINGS:
      Complex interactions exist between the sympathetic and parasympathetic nervous
      system on the atrial electrophysiologic properties. Direct autonomic recordings
      in canine models demonstrated simultaneous sympathovagal discharges are the most
      common triggers of paroxysmal atrial tachycardia and paroxysmal atrial
      fibrillation. Also, intrinsic cardiac autonomic nerve can serve as a sole
      triggering factor for the initiation of atrial fibrillation. Modulation of
      autonomic nervous system (ANS) by electrical stimulation has been tried as a
      treatment strategy clinically and experimentally. Recent studies showed that
      autonomic nervous system modulation can suppress the stellate ganglion nerve
      activity and reduce the incidence of paroxysmal atrial tachyarrhythmias in
      ambulatory dogs. SUMMARY: The autonomic nerve system influences the initiation
      and perpetuation of atrial fibrillation. Scientific advances toward a better
      understanding of the complex interrelationships of the various components of the
      ANS will hopefully lead to improvement of treatments for this common arrhythmia.

PMID- 22139704
TI  - Hepatic endoplasmic reticulum stress in obesity: deeper insights into processes,
      but are they relevant to nonalcoholic steatohepatitis?

PMID- 22139705
TI  - Phosphatidylcholines as regulators of glucose and lipid homeostasis: promises and
      potential risks.

PMID- 22139706
TI  - Infiltrating monocytes versus resident Kupffer cells: do alternatively activated
      macrophages need to be targeted alternatively?

PMID- 22139708
TI  - MicroRNA-200b reverses chemoresistance of docetaxel-resistant human lung
      adenocarcinoma cells by targeting E2F3.
AB  - BACKGROUND: MicroRNAs (miRNAs) have been identified as important
      posttranscriptional regulators involved in various biological and pathological
      processes of cells, but their association with tumor chemoresistance has not been
      fully understood. METHODS: We detected miRNA-200b (miR-200b) expression in
      different lung adenocarcinoma cell lines and then focused on its roles in
      regulation of docetaxel chemoresistance. We also identified E2F3 as a novel
      target of miR-200b. RESULTS: Based on miRNA microarray data, miR-200b was
      identified as the most down-regulated miRNA in docetaxel-resistant SPC-A1/DTX
      cells compared with parental SPC-A1 cells. Ectopic miR-200b expression reversed
      docetaxel chemoresistance of lung adenocarcinoma cells through cell proliferation
      inhibition, apoptosis enhancement, and G(2) /M cell cycle arrest. In a nude mouse
      xenograft model, up-regulation of miR-200b significantly enhanced response of SPC
      A1/DTX cells to docetaxel. Luciferase reporters containing the 3' untranslated
      region sequence of E2F3 messenger RNA were used to demonstrate that miR-200b
      could directly target E2F3. Small interfering RNA-mediated E2F3 knockdown
      revealed similar effects as that of ectopic miR-200b expression. Decreased miR
      200b expression was also detected in tumor tissues sampled from lung
      adenocarcinoma patients treated with docetaxel-based chemotherapy and was proved
      to be correlated with high expression of E2F3, decreased sensitivity to
      docetaxel, and poor prognosis. CONCLUSIONS: Our results suggest that down
      regulation of miR-200b could lead to E2F3 overexpression and in turn contribute
      to chemoresistance of lung adenocarcinoma cells to docetaxel.

PMID- 22139709
TI  - A correlation exists between subchondral bone mineral density of the distal
      radius and systemic bone mineral density.
AB  - BACKGROUND: Intraarticular distal radius fractures are common and risk articular
      congruity owing to disruption of the subchondral bone. Studies regarding
      microstructure and mechanical properties of the distal radius, however, focus
      only on the cortical and trabecular bones in the metaphysis and not on the
      subchondral bone. QUESTIONS/PURPOSES: This study was conducted to (1) quantify
      the regional bone mineral density of the subchondral plate in the distal radius;
      (2) analyze the topographic distribution pattern of the subchondral bone mineral
      density; and (3) evaluate the correlation between the subchondral bone mineral
      density and the potentially related clinical factors of age, height, weight, BMI,
      systemic bone mineral densities, socio-occupational classification, and hand
      osteoarthritis grading. METHODS: Eighty postmenopausal women with a mean age of
      68 years (range, 52-88 years) were enrolled in this study. Digital images of the
      distal radii of the subjects were scanned by conventional CT and processed to
      provide the regional bone mineral density of the subchondral plate using a CT
      osteoabsorptiometry technique. The estimated subchondral bone mineral density was
      analyzed to evaluate the topographic pattern and its correlation with various
      clinical factors, including age, height, weight, BMI, degree of hand
      osteoarthritis, socio-occupational class, and systemic bone mineral density
      measured in the lumbar spine and hip. RESULTS: During topographic analysis of a
      densitometric map, a bicentric distribution of the subchondral bone mineral
      density was found. Among the clinical factors, only the systemic bone mineral
      density measured by dual-energy x-ray absorptiometry in the femur neck and lumbar
      spine had a significant correlation with the subchondral bone mineral density of
      the distal radius. CONCLUSION: Systemic bone mineral density correlates
      substantially with the subchondral bone mineral density of the distal radius as a
      constitutional factor, whereas other local factors arising from the gravitational
      load or joint reaction force are not associated with the subchondral bone mineral
      density of the distal radius. LEVEL OF EVIDENCE: Level II, prognostic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 22139710
TI  - High long-term local control with sacrectomy for primary high-grade bone sarcoma
      in children.
AB  - BACKGROUND: Sacrectomy may offer curative potential for primary sarcomas of the
      sacrum. However, it is unclear whether and to what extent sacrectomies achieve
      local control. QUESTIONS/PURPOSE: We therefore determined the curative potential,
      walking ability, continence control, and quality of life for children after
      sacrectomy for primary bone sarcoma. METHODS: We retrospectively reviewed eight
      children with high-grade primary bone sarcomas treated with sacrectomy. The
      average age of the patients was 14 years (range, 4-18 years). There were six
      Ewing sarcomas and two osteosarcomas. Five patients underwent partial and three
      underwent total sacrectomies with all resection margins free of tumor. We
      recorded local and distant recurrences, functional (Musculoskeletal Tumor Society
      [MSTS] score) and oncologic outcome (survival), walking ability, bladder and
      bowel control, independence, and reintegration in society. The average followup
      was 80 months (range, 54-204 months). RESULTS: Six patients were alive without
      evidence of disease at last followup. Three patients had metastases develop and
      two died of disease 3 and 25 months postoperative. MSTS scores among survivors
      averaged 17.5 points (range, 5-25 points). Seven of the eight patients were able
      to ambulate, two independently. All initially were incontinent, but at last
      followup, two were continent and two were incontinent only under stress.
      Complications occurred in seven of eight, five of whom required additional
      surgery. CONCLUSION: Despite the high incidence of neurologic deficits and
      complications, sacrectomy achieved local control in patients with high-grade bone
      sarcomas. Our observations suggest long-term survival and adequate quality of
      life are possible in the pediatric population. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 22139711
TI  - Competing cardiovascular outcomes associated with electrocardiographic left
      ventricular hypertrophy: the Atherosclerosis Risk in Communities Study.
AB  - BACKGROUND: Individuals with electrocardiographically determined left ventricular
      hypertrophy (ECG LVH) are at risk of multiple cardiovascular disease (CVD)
      outcomes simultaneously. The study sought to characterise the competing
      incidences for subtypes of first CVD events or non-CVD death in those with and
      without ECG LVH. METHODS: Participants in the Atherosclerosis Risk in Communities
      (ARIC) Study were included. ECG LVH was defined according to Sokolow-Lyon
      criteria. Competing Cox models were used to compare hazards for diverse outcomes
      within groups (e.g., among those with ECG LVH) and for a given event between
      groups (ECG LVH vs. no ECG LVH). RESULTS: After 15 years, men with ECG LVH at
      baseline (N=383) had a cumulative incidence of first CVD events and non-CVD
      deaths of 29.2% and 6.1%, respectively (HR 4.86; 95% CI 3.04 to 7.77). In men
      without ECG LVH (N=6576) the incidence of any first CVD event and non-CVD death
      was 18.9% and 6.9%, respectively (HR 2.67; 2.39 to 2.98). Similar associations
      were observed in women (N=381 with and N=8187 without ECG LVH). Coronary heart
      disease (CHD) was the most common first event in men with ECG LVH (15.0%) and
      heart failure was the most common first event in women with ECG LVH (10.5%).
      After adjustment for risk factors including systolic blood pressure, any CVD
      event remained the most likely first event. CONCLUSIONS: Among middle-aged
      individuals with ECG LVH, the most likely first events are CHD in men and heart
      failure in women; these results may have implications for preventive approaches.

PMID- 22139712
TI  - Tandem arrays of TEMPO and nitronyl nitroxide radicals with designed arrangements
      on DNA.
AB  - Herein we describe one-dimensional electron-spin arrays consisting of two
      different organic radicals with the designed arrangement based on the DNA
      sequence. Two mismatch-binding ligands carrying 2,2,6,6-tetramethylpiperidine N
      oxide (TEMPO) and nitronyl nitroxide selectively bind to the predetermined sites
      on double stranded DNA. By using the two mismatch-binding ligands carrying the
      organic radicals as the glue for DNA, electron-spin assembly could be
      successfully synchronized with the hybridization. Periodically and tandemly
      arranged, two kinds of organic radical molecules at designed positions might be
      useful for an approach to build up scalable qubits of electron-spin-based quantum
      computing. The approach using DNA nanostructures as a scaffold to assembly
      functional small molecules can afford one of the promising ways for the future
      application of DNA nanostructures and nanotechnology.

PMID- 22139713
TI  - Relevance of in vitro tests of adhesive and composite dental materials. A review
      in 3 parts. Part 3: in vitro tests of adhesive systems.
AB  - In the third part of this review of laboratory testing, methods of testing
      adhesive systems are evaluated. Test set-ups that are used to analyze the
      restorative material in combination with the adhesive system are presented.
      Currently, there is no standardized protocol available for the evaluation of
      adhesives. This complicates any direct comparisons of values between different
      testing institutes. Therefore, the statistically evaluated ranking of the
      different adhesives is more important than mean values. Depending on the testing
      institute, a correlation between bond strength measurements and clinical outcomes
      may exist. Qualitative analysis of adhesive/tooth interaction can help explain
      the functioning of a system, but the depth of penetration of the adhesive cannot
      predict bond strength. Indirect bond measurements or analyses of the interactions
      of adhesive and composite materials, such as dye penetration or marginal
      analysis, do not correlate or correlate only partially with clinical findings.
      Adhesive systems should be tested in vitro and compared to a well-known standard
      adhesive before they are used in the clinic. Water storage of specimens for
      several months before testing increases the predictability of the bonding
      performance of the tested adhesive.

PMID- 22139714
TI  - Thermochemical properties and phase behavior of halogenated polycyclic aromatic
      hydrocarbons.
AB  - Knowledge of vapor pressure of organic pollutants is essential in predicting
      their fate and transport in the environment. In the present study, the vapor
      pressures of 12 halogenated polycyclic aromatic compounds (PACs), 9
      chlorofluorene, 2,7-dichlorofluorene, 2-bromofluorene, 9-bromofluorene, 2,7
      dibromofluorene, 2-bromoanthracene, 9-chlorophenanthrene, 9-bromophenanthrene,
      9,10-dibromophenanthrene, 1-chloropyrene, 7-bromobenz[a]anthracene, and 6,12
      dibromochrysene, were measured using the Knudsen effusion method over the
      temperature range of 301 to 464 K. Enthalpies and entropies of sublimation of
      these compounds were determined via application of the Clausius-Clapeyron
      equation. The data were also compared with earlier published literature values to
      study the influence of halogen substitution on vapor pressure of PACs. As
      expected, the halogen substitution decreases vapor pressure compared with parent
      compounds but does not necessarily increase the enthalpy of sublimation.
      Furthermore, the decrease of vapor pressure also depends on the substitution
      position and the substituted halogen, and the di-substitution of chlorine and/or
      bromine decreases the vapor pressure compared with single halogen-substituted
      polycyclic aromatic hydrocarbons. In addition, the enthalpy of fusion and melting
      temperature of these 12 PACs were determined using differential scanning
      calorimetry and melting point analysis.

PMID- 22139715
TI  - Anatomical correlates of endonasal surgery for sinonasal malignancies.
AB  - In recent years, endoscopic endonasal techniques have been applied to the
      treatment of sinonasal malignancies. Comprehensive anatomical knowledge is
      essential to preserve oncological principles and minimize surgical morbidity. The
      bones that form the anterior cranial base are pneumatized and the sinuses provide
      surgical corridors for the endoscopic endonasal approach to the skull base.
      During endoscopic endonasal resection of sinonasal malignancies, usually, the
      intranasal portion of the tumor is first debulked to provide visualization of the
      margins and assess the extent of the tumor. Afterwards the tumor is completely
      removed and the margins of resection are defined. In case of dural resection, the
      reconstruction is done with vascularized tissue (septal flap or pericranial
      flap). Sinonasal malignant neoplasms that invade the skull base can be resected
      accordingly to oncological principles using endoscopic endonasal techniques.
      Profound knowledge of the endoscopic anatomy of the ventral cranial base is
      paramount in order to perform a safe resection and reconstruction.

PMID- 22139716
TI  - The contribution of strain patterns in characterization of prostate peripheral
      zone lesions at transrectal ultrasonography.
AB  - BACKGROUND: Elasticity is an important characteristic of tissue. During an
      elastography examination, various strain images of lesions are observed, and a
      suitable classification of strain patterns (SP) may provide vital diagnostic
      information about lesions. Numerous studies have shown that ultrasound
      elastography can improve the detection of prostate cancer, but the diagnostic
      value of SP classification has not yet been fully evaluated. PURPOSE: To
      investigate the contribution of SP on the characterization of prostate peripheral
      zone lesions by transrectal real-time tissue elastography (TRTE) in combination
      with conventional transrectal ultrasonography (TRUS). MATERIAL AND METHODS: One
      hundred and seventy-one patients with suspected prostate cancer underwent TRUS
      and TRTE examinations. The SPs of the suspicious lesions were classified into
      five scores by TRTE according to the degree and distribution of strain. All
      findings were confirmed by transrectal systematic 12-core biopsies and targeted
      biopsies for suspicious areas detecting by TRUS and/or TRTE. RESULTS: One hundred
      and forty-eight of 171 patients had high-quality TRTE imaging and were included
      into the study. When a cut-off point of SP score III was used, the area under the
      receiver-operating characteristic curve (AUC) was, respectively, 0.75 (95% CI:
      0.67-0.83), 0.85 (95% CI: 0.78-0.91) and 0.84 (95% CI: 0.77-0.91) for the
      diagnosis of prostate cancer by TRUS, TRTE and TRTE + TRUS. A linear tendency of
      SP and Gleason scores was observed in scores III-V. The detection rate of
      prostate cancer using TRTE-targeted biopsy (75.8%) was significantly higher than
      that of systematic 12-core biopsy plus TRUS-targeted biopsy (14.5%) (P = 0.00).
      CONCLUSION: This study suggests the significant contribution of SP on
      characterization of prostate peripheral zone lesions and the improvement of TRTE
      targeted biopsy on detection of prostate cancer.

PMID- 22139717
TI  - Atypical pleural tuberculosis presenting as an isolated pleural tuberculoma.
AB  - Pleural tuberculosis is the most common extrapulmonary manifestation of
      tuberculosis, and is generally characterized by an effusion. The effusion is
      usually unilateral and residual pleural thickening or calcification is also
      observed in some cases. Manifestations of multiple pleural tuberculomas without
      associated effusion and history of tuberculosis or antituberculous therapy are
      rare and an isolated pleural tuberculoma is exceedingly rare. Herein, we report
      the first documented case of an isolated pleural tuberculoma, diagnosed by chest
      CT and pathological findings. Although rare, an isolated pleural tuberculoma
      should be added to the differential diagnosis of focal nodular pleural tumors,
      particularly in areas of high tuberculosis prevalence.

PMID- 22139718
TI  - Crossed cerebellar hyperperfusion after MELAS attack followed up by whole brain
      continuous arterial spin labeling perfusion imaging.
AB  - Crossed cerebellar hyperperfusion (CCH) is detected in patients with epilepsy by
      brain perfusion studies including single photon emission computed tomography and
      positron emission tomography. In addition, brain perfusion can be studied with
      arterial spin labeling (ASL), which is a non-invasive MRI perfusion method that
      quantitatively measures cerebral blood flow per unit tissue mass. We followed up
      a 47-year-old patient with mitochondrial myopathy, encephalopathy, lactic
      acidosis, and stroke-like episodes (MELAS) by continuous arterial spin labeling
      technique, which showed crossed cerebellar hyperperfusion after acute stroke-like
      episode. This cerebellar hyperperfusion normalized in the follow-up.

PMID- 22139719
TI  - Dorsal agenesis of the pancreas - a rare cause of abdominal pain and insulin
      dependent diabetes.
AB  - Dorsal agenesis of the pancreas is a rare congenital disorder. We report a case
      of a 65-year-old man with mild abdominal pain and insulin-dependent diabetes
      mellitus. Computed tomography (CT) of the abdomen showed a short pancreas with no
      pancreatic tissue ventral to the splenic vein. Magnetic resonance
      cholangiopancreatography (MRCP) visualized the absence of a dorsal duct system
      and confirmed the suspicion of complete agenesis of the dorsal pancreas.
      Endoscopic ultrasound (EUS) was also performed to rule out pancreatic malignancy.

PMID- 22139720
TI  - CT-guided percutaneous drainage within intervertebral space for pyogenic
      spondylodiscitis with psoas abscess.
AB  - BACKGROUND: Reports on CT-guided percutaneous drainage within the intervertebral
      space for pyogenic spondylodiscitis with a secondary psoas abscess are limited.
      PURPOSE: To evaluate CT-guided percutaneous drainage within the intervertebral
      space for pyogenic spondylodiscitis and a secondary psoas abscess in which the
      two sites appear to communicate. MATERIAL AND METHODS: Eight patients with
      pyogenic spondylodiscitis and a secondary psoas abscess showing communication
      with the intradiscal abscess underwent CT-guided percutaneous drainage within the
      intervertebral space. The clinical outcome was retrospectively assessed. RESULTS:
      An 8-French pigtail catheter within the intervertebral space was successfully
      placed in all patients. Seven patients responded well to this treatment. The one
      remaining patient who had developed septic shock before the procedure died on the
      following day. The mean duration of drainage was 32 days (13-70 days). Only one
      patient with persistent back pain underwent surgery for stabilization of the
      spine after the improvement of inflammation. Among seven patients responding
      well, long-term follow-up (91-801 days, mean 292 days) was conducted in six
      patients excluding one patient who died of asphyxiation due to aspiration
      unrelated to the procedure within 30 days after the procedure. In these six
      patients, no recurrence of either pyogenic spondylodiscitis or the psoas abscess
      was noted. CONCLUSION: CT-guided percutaneous drainage within the intervertebral
      space can be effective for patients with pyogenic spondylodiscitis and a
      secondary psoas abscess if the psoas abscess communicates with the intradiscal
      abscess.

PMID- 22139721
TI  - Digital tomosynthesis for aortic arch calcification evaluation: performance
      comparison with chest radiography with CT as the reference standard.
AB  - BACKGROUND: Recently developed digital tomosynthesis has shown improved detection
      of pulmonary lesions with a radiation dose comparable to conventional CR but with
      a much lower radiation dose than CT. PURPOSE: To compare the diagnostic
      performance of digital tomosynthesis (DT) with that of chest radiography (CR) for
      the detection of aortic arch calcification (AAC). MATERIAL AND METHODS: The study
      included 100 patients who underwent multidetector computed tomography (MDCT), DT,
      and CR (DT and CR were obtained within one week of CT examination). We evaluated
      and compared the diagnostic performances of DT and CR for the detection of AAC
      with MDCT as the reference standard. The extent (four grades 0-3) of AAC on DT
      and CR was also compared with CT calcium score. Inter-observer agreement was
      analyzed by using kappa statistics. RESULTS: On DT, overall accuracy for AAC was
      superior to that of CR (94% and 71%, respectively, P < 0.01). Inter-observer
      agreement was good with DT and CR (kappa values = 0.74 and 0.62, respectively)
      for the presence of AAC, and good with DT and moderate with CR (kappa value =
      0.64 and 0.53, respectively) for AAC grading. The overall correlation coefficient
      on AAC grading between DT and CT (calcium score) was superior to that between CR
      and CT (0.90 and 0.60, respectively). CONCLUSION: DT is superior to CR for
      detection and extent evaluation of AAC.

PMID- 22139722
TI  - Contrast-induced nephropathy: controlled study by differential GFR measurement in
      hospitalized patients.
AB  - BACKGROUND: Without appropriate control measures, contrast-induced nephropathy
      (CIN) incidence has been claimed to be overestimated. PURPOSE: To evaluate the
      relationship and the difference between differential serum creatinine (DsCr),
      which is currently surrogating as a marker of CIN, and measured differential GFR
      values as a control measure (DGFR) in hospitalized patients. MATERIAL AND
      METHODS: GFR was measured two times by Tc-99m DTPA, before and 48 h after
      contrast media (CM), along with sCr and BUN in 35 inpatients (22 men, 13 women,
      mean age +/- SD = 61 +/- 14) with no known chronic kidney disease. RESULTS:
      Relationship was moderate between GFR and sCr (R = 0.50, P < 0.01) in the study
      population. Pre-CM vs. post-CM values of GFR, sCr and BUN were not statistically
      different as (mean +/- SD); 78 +/- 36 vs. 73 +/- 35 mL/min/1.73m(2), 0.95 +/-
      0.26 vs. 0.94 +/- 0.26 mg/dl and 21 +/- 16 vs. 19 +/- 13 mg/dl, respectively, in
      the study group. According to basal GFR values, 14 patients (40%) seemed carrying
      risk of CIN (GFR < 60 mL/min/1.73m(2)) in whom only two had sCr >1.5 mg/dl.
      Twenty-five patients (71%) had discordant results in relation to DsCr and DGFR
      and two of them had CIN according to classical definition of DsCr, although
      having basal sCr <1.1 mg/dl. Yet, both had low, but stable GFR values. None of
      patient from the study group underwent hemodialysis. CONCLUSION: Significant
      discordance was observed between differential serum creatinine and measured
      differential GFR in hospitalized patients, suggesting that CIN incidence
      calculations only based on hospital registry may carry risk of error.

PMID- 22139724
TI  - Current world literature.

PMID- 22139723
TI  - Clinical utility of screening for clinical depression and bipolar disorder.
AB  - PURPOSE OF REVIEW: Screening for clinical depression and bipolar disorder remains
      controversial. Screening is usually based on finding discriminating symptoms, but
      not all tools perform equally well. Clinicians should be able to assess the
      clinical utility of screening tests as well as their accuracy and acceptability.
      RECENT FINDINGS: Screening for depression using the Patient Health Questionnaire
      (PHQ) has been extensively examined. Four main versions of scoring the PHQ exist.
      The two-item PHQ2, the nine-item PHQ9, the PHQ DSM-IV algorithm, and the two-step
      PHQ2 then PHQ9. Recent results suggest that the PHQ9 is more accurate than the
      PHQ2, and that the algorithm scoring method is preferred to the linear cut-off
      score. The two-step procedure has promise, but it has not been adequately tested.
      Two screening questions may be a useful compromise in medical settings, as they
      take less than 2 min, but about a quarter of patients do not receive screening
      even when implemented systematically. Alternative customized questionnaires have
      been developed in medical settings such as the Depression Screening in
      Parkinson's Disease DESPAR and Neurological Disorders Depression Inventory for
      Epilepsy (NDDI-E). Screening for bipolar disorders is an even greater challenge
      than screening for unipolar depression. Screening in primary care and the
      community has low positive predictive value. Screening in high-risk samples, such
      as those with known depression is somewhat more successful, but not yet
      sufficiently accurate to be used alone. SUMMARY: Screening for depression can
      bring added value to routine unassisted recognition, but only if followed by good
      quality treatment. Screening for bipolar disorder is not yet sufficiently
      accurate to be used reliably in clinical practice.

PMID- 22139726
TI  - Establishment of a standardized gene-expression analysis system using formalin
      fixed, paraffin-embedded, breast cancer specimens.
AB  - BACKGROUND: It has recently being emphasized that gene-expression profiles are
      important clinical decision-making tools, and as such must be standardized across
      hospital laboratories in the same way as pathological investigations. In this
      study our objective was to independently establish a standardized gene-expression
      assay system using routinely processed, formalin-fixed, paraffin-embedded (FFPE)
      tissues. METHODS: To verify gene expression by quantitative real-time polymerase
      chain reaction, the most stably expressed reference genes were explored using 30
      matched FFPE and fresh frozen (FF) tissues. FFPE specimens from 290 female breast
      cancer patients were used for further RNA extraction; ESR1 and PGR were measured
      using 203 matched FFPE and FF specimens and normalized to these reference genes.
      RESULTS: RNA extracted from FFPE specimens was highly degraded, but almost the
      same selection of genes was identified-TAF, PUM1, and ACTB, and, for FFPE
      specimens only, FKBP15. Eventually 88.6% of all the FFPE samples were identified
      as quantitatively and qualitatively adequate for downstream analysis. The results
      revealed good correlation and excellent concordance with ERalpha and PgR protein
      expression evaluated by immunohistochemistry. Moreover, the distribution of ESR1
      and PGR gene expression values was quite reasonable, reflecting differences
      between the transcriptional mechanisms of the respective genes. CONCLUSIONS: We
      successfully confirmed that our gene-expression analysis system provides good
      quality control for larger scale assays; it may therefore be suitable for
      development, in the near future, of a multiple gene assay as a routine clinical
      judgment tool.

PMID- 22139728
TI  - The roles of TGF-beta signaling in carcinogenesis and breast cancer metastasis.
AB  - Transforming growth factor-beta (TGF-beta) ligand is a multifunctional growth
      factor that regulates various cell behavior, such as cell proliferation,
      differentiation, migration, and apoptosis. Because TGF-beta is a potent growth
      inhibitor, abnormalities in TGF-beta signaling result in carcinogenesis. In
      addition to tumor suppressor function, TGF-beta acts as an oncogenic factor. In
      particular, TGF-beta signaling plays an important role during metastasis of
      breast cancer. Recently, epithelial-mesenchymal transition (EMT) has been shown
      to confer malignant properties such as cell motility and invasiveness to cancer
      cells and plays crucial roles during cancer metastasis. Moreover, breast stem
      like cells exhibit EMT properties. Because TGF-beta is a potent regulator of EMT
      as well as cell stemness, TGF-beta signaling might play a crucial role in the
      regulation of breast cancer stem cells.

PMID- 22139727
TI  - Prognostic factors for stage IV hormone receptor-positive primary metastatic
      breast cancer.
AB  - BACKGROUND: The purpose of this work was identify potential prognostic factors
      for survival in patients with primary metastatic hormone receptor-positive breast
      cancer undergoing endocrine therapy (ET) as first-line treatment. METHODS: We
      investigated the clinical and pathological characteristics of 69 newly diagnosed
      stage IV hormone receptor-positive breast cancer patients undergoing ET between
      1999 and 2009, and correlated these factors with disease progression and overall
      survival. RESULTS: Multivariate regression analysis revealed that progesterone
      receptor (PgR) positivity (hazard ratio (HR) 0.248; p = 0.001) and clinical
      benefits of first-line ET (HR 0.386; p = 0.008) were significant prognostic
      factors for survival. When first-line ET was not effective, patients for whom
      second-line ET was effective survived significantly longer than those for whom
      second-line ET was not effective (median survival time, 45.3 vs. 25.8 months; p =
      0.0411). CONCLUSIONS: PgR positivity and clinical benefits of first-line ET were
      independent prognostic factors for patients with hormone receptor-positive stage
      IV breast cancer. Moreover, the benefits of second-line ET in patients with a
      tumor resistant to first-line ET suggests the existence of drug-specific
      resistance to ET.

PMID- 22139729
TI  - Sample size calculations for ROC studies: parametric robustness and Bayesian
      nonparametrics.
AB  - Methods for sample size calculations in ROC studies often assume independent
      normal distributions for test scores among the diseased and nondiseased
      populations. We consider sample size requirements under the default two-group
      normal model when the data distribution for the diseased population is either
      skewed or multimodal. For these two common scenarios we investigate the potential
      for robustness of calculated sample sizes under the mis-specified normal model
      and we compare to sample sizes calculated under a more flexible nonparametric
      Dirichlet process mixture model. We also highlight the utility of flexible models
      for ROC data analysis and their importance to study design. When nonstandard
      distributional shapes are anticipated, our Bayesian nonparametric approach allows
      investigators to determine a sample size based on the use of more appropriate
      distributional assumptions than are generally applied. The method also provides
      researchers a tool to conduct a sensitivity analysis to sample size calculations
      that are based on a two-group normal model. We extend the proposed approach to
      comparative studies involving two continuous tests. Our simulation-based
      procedure is implemented using the WinBUGS and R software packages and example
      code is made available.

PMID- 22139730
TI  - Construction of a genetically engineered microorganism that simultaneously
      degrades organochlorine and organophosphate pesticides.
AB  - Field contamination with pesticide mixtures of organophosphates (OPs) and
      organochlorines (OCs) is becoming global issues to be solved urgently. The
      strategy of utilizing engineered microorganisms that have an ability to
      simultaneously degrade OPs and OCs has increasingly received great interest. In
      this work, an OP degradation gene (mpd) and an OC degradation gene (linA) were
      simultaneously introduced into Escherichia coli by using two compatible plasmids,
      resulting in strains with both OP degradation and OC degradation capabilities. To
      overcome the potential substrate uptake limitation, MPH was displayed on the cell
      surface of Escherichia coli using the N- and C-terminal domains of ice nucleation
      protein (INPNC) as an anchoring motif. The surface localization of INPNC-MPH was
      verified by cell fractionation, Western blot, proteinase accessibility, and
      immunofluorescence microscopy. Furthermore, both LinA and green fluorescent
      protein (GFP) were functionally co-expressed in the MPH-displaying Escherichia
      coli. The engineered Escherichia coli degraded OPs as well as OCs rapidly, and it
      can be easily monitored by GFP fluorescence.

PMID- 22139731
TI  - Further stabilization of Leu155 mutant thermolysins by mutation of an
      autodegradation site.
AB  - The autodegradation-resistant mutant thermolysins (TLNs), L155A (Leu(155) to Ala)
      and L155S (Leu(155) to Ser), were previously constructed by site-directed
      mutagenesis to enhance thermostability. These mutations suppressed
      autodegradation at position 154-155, resulting in increased thermostability.
      However, a new autodegradation site became apparent in these mutant TLNs, at
      position 155-156. In this study, further stabilization of the mutant TLNs to
      suppress this new autodegradation was attempted by the substitution of Ile(156)
      to Asp and Val (L155A-I156N, L155A-I156V, L155S-I156N, and L155S-I156V). SDS-PAGE
      analysis showed that the autodegradation at 155-156 of all double-mutant TLNs was
      suppressed. Thermostability at 80  degrees C was enhanced in all double-mutant
      TLNs (half-life at 80  degrees C: WT, 18.3 min; L155A, 25.0 min; L155S, 24.0 min;
      L155A-I156N, 60.8 min; L155A-I156V, 62.4 min; L155S-I156N, 93.3 min; and L155S
      I156V, 40.0 min), and k (cat)/K (m) values were: WT, 220; L155A, 240; L155S, 123;
      L155A-I156N, 62; L155A-I156V, 760; L155S-I156N, 240; and L155S-I156V, 520 min(-1)
      mM(-1).

PMID- 22139732
TI  - A hydrogen peroxide biosensor based on direct electrochemistry of hemoglobin in
      palladium nanoparticles/graphene-chitosan nanocomposite film.
AB  - Thermally two-dimensional lattice graphene (GR) and biocompatibility chitosan
      (CS) act as a suitable support for the deposition of palladium nanoparticles
      (PdNPs). A novel hydrogen peroxide (H(2)O(2)) biosensor based on immobilization
      of hemoglobin (Hb) in thin film of CS containing GR and PdNPs was developed. The
      surface morphologies of a set of representative membranes were characterized by
      means of scanning electron microscopy and showed that the PdNPs are of a sphere
      shape and an average diameter of 50 nm. Under the optimal conditions, the
      immobilized Hb showed fast and excellent electrocatalytic activity to H(2)O(2)
      with a small Michaelis-Menten constant of 16 MUmol L(-1), a linear range from 2.0
      * 10(-6) to 1.1 * 10(-3) mol L(-1), and a detection limit of 6.6 * 10(-7) mol L(
      1). The biosensor also exhibited other advantages, good reproducibility, and long
      term stability, and PdNPs/GR-CS nanocomposites film would be a promising material
      in the preparation of third generation biosensor.

PMID- 22139733
TI  - Chemiluminescence response of murine macrophages on multilayer microfluidic
      chips.
AB  - We have demonstrated an integrated platform for microfluidics and
      chemiluminescence (CL) detection that is capable of parallel cell culture,
      convenient liquid manipulation, and sensitive chemiluminescent detection. Luminol
      dependent CL responses induced by three different stimuli, phytohemagglutinin
      (PHA), concanavalin A (ConA), and lipopolysaccharides (LPS), which can evoke a CL
      response in macrophages, were evaluated on this microfluidic chip. We studied the
      dose-dependent effect of these three stimuli on CL response in murine
      macrophages. PHA produced the highest CL response compared to LPS and ConA. The
      CL intensity produced by PHA was 6.85 and four times higher than that by LPS and
      ConA, respectively, at the low concentration of 100 MUg/ml. We have found
      microfluidic based CL to be a very useful screening tool, which is less laborious
      and more sensitive. This microfluidic system is disposable and capable of rapid
      device prototyping; it may prove to be very useful in clinical and pharmaceutical
      applications.

PMID- 22139734
TI  - Drug delivery and imaging with polydiacetylene micelles.
AB  - This concept article summarizes our recent findings regarding photopolymerized
      micelles obtained from the self-assembly of diacetylene-containing amphiphiles.
      Their synthesis and characterization are presented as well as some biomedical
      applications, such as tumor imaging and drug delivery. Finally, ongoing studies
      and future challenges are briefly discussed.

PMID- 22139735
TI  - The prognostic difference of monoallelic versus biallelic deletion of 13q in
      chronic lymphocytic leukemia.
AB  - BACKGROUND: Fluorescence in situ hybridization can detect genomic abnormalities
      in up to 80% of cases and provides prognostic information on patients with
      chronic lymphocytic leukemia (CLL). Although 13q deletion as the sole abnormality
      has been found to confer a favorable prognosis, there are little data as to
      whether there is a difference in prognostic value between monoallelic versus
      biallelic deletion of 13q. METHODS: The authors reviewed the electronic database
      for patients with CLL who carried the 13q deletion as the sole abnormality and
      presented to The University of Texas MD Anderson Cancer Center (MDACC). Untreated
      patients were separated into 2 groups: those having monoallelic versus those with
      biallelic deletion of 13q. Using Mann-Whitney, chi-square, and Kaplan-Meier
      analysis, the baseline quantitative and qualitative variables for each group,
      along with the time from presentation to MDACC to treatment, were compared.
      RESULTS: A total of 176 patients were identified; 143 patients had a monoallelic
      deletion of 13q, whereas 33 patients had a biallelic deletion. The only
      significantly different values between the groups were albumin (4.5 g/dL vs 4.4
      g/dL; P = .01) and zeta-chain-associated protein kinase 70 (ZAP70) expression
      (1.7% vs 4.8%; P = .010). The median time from fluorescence in situ hybridization
      analysis to treatment in both the monoallelic and biallelic groups had not been
      reached (P = not significant). CONCLUSIONS: Except for inconsequential
      differences in albumin and ZAP70 expression, there was no difference in the
      baseline characteristics between patients with CLL who had monoallelic or
      biallelic deletion of 13q. In addition, there was no significant difference in
      endpoints, including time to treatment.

PMID- 22139736
TI  - Accumulation of PAHs and synthetic musk compound in minke whales (Balanoptera
      acutorostrata) and long-beaked common dolphins (Delphinus capensis) from Korean
      coastal waters.
AB  - Information on the occurrence and accumulation profiles of polycyclic aromatic
      hydrocarbons (PAHs) and synthetic musk compounds (SMCs) in marine mammals is
      scarce. In the present study, we recorded the concentrations and profiles of PAHs
      and SMCs in liver tissue and blubber from minke whales and common dolphins from
      Korean coastal waters. The overall concentrations of PAHs and SMCs in blubber
      from both cetacean species were approximately three to five times higher than
      those in liver tissues. Residue levels of PAHs were lower, whereas levels of SMCs
      were relatively higher than those reported in other studies. Lack of species- and
      sex-dependent differences in the concentrations of PAHs and SMCs were found.
      Naphthalene and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-r-2
      benzopyran (HHCB) were predominant compounds in all the samples for PAHs and
      SMCs, respectively. The concentrations of PAHs and SMCs were significantly
      correlated with each other, but were not correlated with body size of cetaceans.
      The present data provide valuable information on the exposure of Korean cetaceans
      to PAHs and SMCs.

PMID- 22139737
TI  - The effect of Parodontax(r) on the MMP-8 concentration in gingivitis patients.
AB  - The aim of the study was to evaluate the efficacy of Parodontax(r) (GlaxoSmith
      Kline, Buhl, Germany) on the signs gingival inflammation and the enzyme activity
      of matrix metalloproteinase-8 (aMMP-8) in the gingival crevicular fluid. After
      approval by the ethics commission, a total of 50 volunteers participated in the
      study; group 1 (n = 25, age: 43 +/- 12 years) with moderate gingivitis (BOP +)
      and group 2 (n = 25, age: 29 +/- 11 years) with clinically healthy gingival
      conditions (BOP -). After obtaining anamnestic data, the dental examination
      included assessment of oral hygiene (Quigley & Hein 1962), gingival inflammation
      (Saxer & Muhlemann 1975), probing pocket depth and clinical attachment level.
      Gingival crevicular fluid was collected from both groups. A quantitative
      assessment of aMMP-8 in the gingival crevicular fluid samples was performed
      (DentoAnalyzer, Dentognostics GmbH, Jena, Germany). Study participants were
      instructed to use only Parodontax(r). After three weeks, all parameters were
      measured again. The aMMP-8 values of group 1 were significantly reduced after the
      use of Parodontax(r) toothpaste and mouthwash (p < 0.001; baseline median 41.25
      +/- 38.16 ng/ml, final post-treatment median 7.73 +/- 7.58 ng/ml aMMP-8 eluate;
      group 2: baseline median 3.75 +/- 3.16 ng/ml, final post-treatment median 3.73 +/
      1.54 ng/ml aMMP-8 eluate). Gingival inflammation and plaque accumulation were
      reduced. It was shown that Parodontax(r) was effective in reducing the enzymatic
      activity of inflammation.

PMID- 22139738
TI  - Detailed anatomy of the capsulopalpebral fascia.
AB  - This study was designed to elucidate the detailed anatomy of the capsulopalpebral
      fascia (CPF) and capsulopalpebral head (CPH), and their relationships to the
      inferior rectus muscle (IRM). In this cohort study, 40 eyes from 20 cadavers were
      observed macroscopically. Dissection was carried out from the CPF origin to its
      insertion, and the CPF origin pattern was photographed in each specimen. The
      width, length, and tensile strength of the CPF were measured. The CPF originated
      25.07 +/- 1.07 mm laterally and 24.86 +/- 1.10 mm medially from the origin of the
      IRM and extended to the lower border of the inferior oblique muscle, and it
      firmly adhered to the IRM surface and formed into the CPH. The CPH was 4.31 +/-
      0.86 mm laterally and 6.18 +/- 1.94 mm medially in length and 7.47 +/- 0.81 mm in
      width. The CPF originated from the total width or 3/4 temporal part of the IRM in
      32 (80%) of 40 faces. There was asymmetry in the pattern of the CPF origin
      between the left and right eyes in 4 of 20 paired specimens (20%). The tensile
      strength of the posterior layer was 19.12 +/- 11.22 N, which was significantly
      higher than that of the anterior layer (8.59 +/- 3.88 N) (P = 0.001). This study
      provided a good understanding of the CPF structures conducive to performing IRM
      surgery.

PMID- 22139739
TI  - A hierarchical rank test for crossover trials with censored data.
AB  - We propose an approach to analyze survival time in a crossover clinical trial by
      performing a primary ranking on whether events occur and a secondary ranking on
      event times. This hierarchical ranking method is meant to reflect the idea that
      the goal of therapy is to prevent a clinical event and, failing that, to delay
      the occurrence of the event, hopefully for a substantial amount of time. We
      compare our approach with other methods including one method proposed by Feingold
      and Gillespie, a recommended procedure. The power is similar in many settings,
      but the hierarchical ranking can have substantially greater power under certain
      censoring patterns and also under a cure model, or models where treatment induces
      a substantial delay in some fraction of patients. We additionally feel that the
      hierarchical ranking method should be more clinically relevant in many settings.
      The method can also be applied to continuous outcomes censored by a limit of
      detection, such as HIV viremia.

PMID- 22139740
TI  - Do arteriovenous fistulae cause technical/local complications after renal
      transplantation?

PMID- 22139741
TI  - The middle arm arteriovenous fistula is an additional option to expand autogenous
      hemodialysis access.
AB  - PURPOSE: The native arteriovenous fistula is the gold standard for hemodialysis
      access. Unfortunately, the wrist fistula is often not practical and the upper arm
      fistula is hindered by several complications. The aim of this study is to assess
      the safety of the middle-arm fistula as additional native access. METHODS: We
      reviewed and compared the patency rates at 12, 48, and 60 months of distal,
      middle, and upper arm fistula performed from January 2003 to December 2008. For
      diabetic and old patients we compared distal and middle-arm fistulas. RESULTS: Of
      273 native access, 149 (54.6%) were distal, 92 (33.7%) middle-arm, and 32 (11.7%)
      upper fistula. Patency rates were 81%, 58%, and 52% for distal, 85%, 69%, and 69%
      for middle-arm, and 82%, 46%, and 29% for upper arm fistula (P NS). Patency rates
      were 92%, 70%, and 54% in middle-arm fistula as first access and 80%, 71%, and
      71% in middle-arm fistula as a rescue access (P NS). Among patients > 75 years
      patency rates were 78%, 62%, and 62% for distal and 87%, 67%, and 67% for middle
      arm fistula. Among diabetic subjects patency rates were 81%, 58%, and 58% for
      middle-arm and 65%, 57%, and 57% for distal fistula at 12, 48, and 60 months (P
      NS) respectively. CONCLUSIONS: A middle-arm fistula is as safe as a distal
      fistula among dialyzed patients, even diabetic and elderly. This could be
      considered a reliable option to expand native accesses.

PMID- 22139742
TI  - Repair of damaged connectors of tunneled cuffed catheters with a two-piece
      adaptor for peritoneal dialysis.
AB  - PURPOSE: Although catheter use exposes the patient to several complications,
      tunneled cuffed catheters are widely applied for temporary or long-term vascular
      access. The aim of the study was to establish the rate of tunneled dialysis
      catheter damage and report our experience with breakage repair. METHODS: All 363
      cuffed tunneled hemodialysis catheters inserted into 309 patients from May 2000
      to December 2008 were followed up. When connector damage was encountered, repair
      with a two-piece adaptor for peritoneal dialysis was attempted. RESULTS:
      Mechanical breakage occurred in 33 (9.1%) of catheters with an incidence of
      0.36/1000 catheter-days. The most frequent was connector damage, found in 25
      cases (67.6%). Catheter repair using a peritoneal dialysis Luer adaptor was
      performed with good early and long-term outcome. CONCLUSIONS: Tunneled catheter
      breakage is a relatively rare complication. Catheter repair using the adaptor for
      peritoneal dialysis is easy to perform, safe, and cost-effective.

PMID- 22139743
TI  - Vascular access type, health-related quality of life, and depression in
      hemodialysis patients: a preliminary report.
AB  - PURPOSE: Arteriovenous fistulas (AVF) are the vascular access of choice for
      hemodialysis (HD) compared with arteriovenous grafts (AVG) and central venous
      catheters (CVC). In spite of increasing recognition of importance of a patient's
      perception of health-related quality of life (HRQOL) and depression, few studies
      have assessed the association of vascular access type with HRQOL and depression.
      The purpose of our study was to examine HRQOL and depression among patients with
      different vascular access. METHODS: Severity of symptoms of depression and HRQOL
      were assessed by Beck Depression Inventory (BDI) and Short Form-36 (SF-36),
      respectively. Vascular access was reported as one of three options; AVF, AVG, and
      CVC. RESULTS: In total, 136 patients were included; 104 had AVF, 15 had AVG, and
      17 had CVC. BDI and HRQOL parameters differed among patients with different
      vascular access types. In post hoc analysis, BDI and HRQOL subscales were not
      different between patients with AVF and AVG. Patients with CVC had lower physical
      functioning (P:.001), role-physical limitation (P:.015), general health
      perception (P:.017), vitality (P:.010), social functioning (P:.004), role
      emotional (P:.008), mental health (P:.001), physical component summary score
      (P:.017), and mental component summary score (P:.006) when compared to patients
      with AVF. Patients with CVC had lower physical functioning (P:.044), role
      emotional (P:.044) and mental health scores (P:.04) when compared to patients
      with AVG. CONCLUSIONS: Having a CVC may negatively influence HRQOL in HD
      patients. Vascular access type does not seem to be related to depressed mood in
      HD.

PMID- 22139745
TI  - Targeting IgE in asthma.
AB  - PURPOSE OF REVIEW: IgE plays a pivotal role in allergic asthma especially in the
      acute response to antigen and in the propagation of airway inflammation.
      Therefore, it has become apparent that targeting this antibody and blocking its
      function may lead to significant clinical effects in some patients with the
      disease. In this review, we describe the role of IgE in asthma and provide an
      update on the therapeutic implications of targeting this mediator in patients
      with severe allergic disease. We also outline future needs of research in this
      area. RECENT FINDINGS: Several randomized clinical trials as well as
      observational real-world studies have confirmed the long-term efficacy of
      omalizumab in improving clinical outcomes when added to guideline-recommended
      maintenance of asthma medications (inhaled corticosteroids and long-acting beta2
      agonists) in patients with moderate-to-severe asthma. Recent pooled data from
      randomized clinical trials and from a large prospective cohort study provide
      reassurance about the long-term safety of omalizumab. Future research should
      explore the long-term effects of omalizumab on the natural history of the disease
      and identify more accurate predictors of response to this treatment. SUMMARY: The
      anti-inflammatory effects of omalizumab at different sites of allergic
      inflammation and its clinical benefits in patients with allergic asthma emphasize
      the fundamental importance of IgE in allergic inflammation.

PMID- 22139746
TI  - Current world literature.

PMID- 22139744
TI  - Bone anabolic agents for the treatment of multiple myeloma.
AB  - The majority of patients with multiple myeloma develop bone osteolytic lesions,
      which may lead to severe complications, including pain and fractures. The
      pathogenesis of bone disease depends on uncoupled bone remodeling, characterized
      by increased bone resorption due to upregulation of osteoclast activity and
      decreased bone formation due to osteoblast inhibition. In myeloma, impaired
      osteoblast differentiation and increased apoptosis have been described.
      Responsible for these effects are integrin-mediated adhesion to tumor cells and
      soluble factors, including WNT antagonists, BMP2 inhibitors and numerous
      cytokines. Based on the evidence of osteoblast suppression in myeloma, bone
      anabolic agents have been developed and are currently undergoing clinical
      evaluation. Due to bidirectional inhibitory effects characterizing tumor cells
      and osteoblasts interactions, agents targeting osteoblasts are expected to reduce
      tumor burden along with improvement of bone health. This review summarizes the
      current knowledge on osteoblast inhibition in myeloma and provides an overview on
      the clinical grade agents with bone anabolic properties, which represent new
      promising therapeutic strategies in myeloma.

PMID- 22139748
TI  - Nested canalyzing depth and network stability.
AB  - We introduce the nested canalyzing depth of a function, which measures the extent
      to which it retains a nested canalyzing structure. We characterize the structure
      of functions with a given depth and compute the expected activities and
      sensitivities of the variables. This analysis quantifies how canalyzation leads
      to higher stability in Boolean networks. It generalizes the notion of nested
      canalyzing functions (NCFs), which are precisely the functions with maximum
      depth. NCFs have been proposed as gene regulatory network models, but their
      structure is frequently too restrictive and they are extremely sparse. We find
      that functions become decreasingly sensitive to input perturbations as the
      canalyzing depth increases, but exhibit rapidly diminishing returns in stability.
      Additionally, we show that as depth increases, the dynamics of networks using
      these functions quickly approach the critical regime, suggesting that real
      networks exhibit some degree of canalyzing depth, and that NCFs are not
      significantly better than functions of sufficient depth for many applications of
      the modeling and reverse engineering of biological networks.

PMID- 22139749
TI  - Altered levels of trace elements in acute lung injury after severe trauma.
AB  - Trace element (TE) supplementation can reduce the incidence of multiple organ
      failure after severe trauma. The lung plays a main role in post-injury multiple
      organ failure. In the present study, the relationship between TEs and acute lung
      injury (ALI) post-injury was investigated in a rabbit model of severe trauma with
      an injury severity score of 27. New Zealand white rabbits were randomly assigned
      to trauma-control, trauma-TE groups, and a control group. During days 1-5 post
      trauma, each rabbit in the trauma-TE group received 0.1 ml multi-TE compound
      intraperitoneally to give a daily dose of 32.50 mg/kg of Zn, 6.35 mg/kg of Cu,
      1.38 mg/kg of Mn, and 0.16 mg/kg of Se. Concentrations of blood and lung selenium
      (Se), copper (Cu), zinc (Zn), and manganese (Mn) were measured at 6 and 24 h, as
      well as 3, 6, 9, and 14 days after trauma. Levels of glutathione peroxidase
      (GPx), total superoxide dismutase (SOD), Cu/Zn superoxide dismutase (Cu/Zn-SOD),
      and malondialdehyde (MDA) in serum and lung tissue and the level of intercellular
      adhesion molecular-1 (ICAM-1) in serum were detected simultaneously. In addition,
      the lung coefficient (LC) and the lung permeation index (LPI) were measured.
      Serum and lung Zn, Se, and Mn levels decreased dramatically by 6 h after trauma
      in both experimental groups. Cu showed no significant changes after trauma. The
      serum and lung GPx and SOD levels in the experimental group decreased
      significantly on days 1 and 3, respectively. Serum and lung MDA began to increase
      on day 3 in the trauma group but increased less after TE supplementation. Serum
      ICAM-1 peaked on day 6 in the experimental group. LC and LPI increased gradually
      post-trauma, peaking on days 6 and 9, respectively. In conclusion, an acute lung
      injury causes declines of the levels of TEs in serum and lung which can be
      significantly prevented by TE supplementation and which can also mitigate some of
      the morphological and biomechanical changes in ALI.

PMID- 22139750
TI  - Stable N-heterocyclic carbene (NHC)-palladium(0) complexes as active catalysts
      for olefin cyclopropanation reactions with ethyl diazoacetate.
AB  - The Pd(0) complexes [(NHC)PdL(n)] (NHC=N-heterocyclic carbene ligand; L=styrene
      for n=2 or PR(3) for n=1) efficiently catalyse olefin cyclopropanation by using
      ethyl diazoacetate (EDA) as the carbene source with activities that improve on
      previously described catalytic systems based on this metal. Mechanistic studies
      have shown that all of these catalyst precursors deliver the same catalytic
      species in solution, that is, [(IPr)Pd(sty)], a 14e(-) unsaturated intermediate
      that further reacts with EDA to afford [(IPr)Pd(=CHCO(2)Et)(sty)], from which the
      cyclopropane is formed.

PMID- 22139751
TI  - Serial measurement of cardiac troponin T using a highly sensitive assay in
      patients with chronic heart failure: data from 2 large randomized clinical
      trials.
AB  - BACKGROUND: Cardiac troponins are emerging as important prognostic markers in
      chronic cardiovascular conditions like stable coronary artery disease or chronic
      heart failure (HF). Less is known about the relation between serial measurements
      of high-sensitivity cardiac troponin T (hs-cTnT) and future events in HF. We
      determined the association between changes over time in hs-cTnT and outcome in
      patients with chronic HF. METHODS AND RESULTS: We analyzed 5284 patients with
      chronic HF from 2 independent randomized clinical trials, the Valsartan Heart
      Failure Trial (Val-HeFT) (n=4053) and the Gruppo Italiano per lo Studio della
      Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial
      (n=1231). hs-cTnT was measured at randomization and after 3 months (GISSI-HF) or
      4 months of follow-up (Val-HeFT). The association between changes over time of hs
      cTnT and various outcomes was tested in multivariable models. In both studies,
      increases in hs-cTnT levels over time were associated with age, diabetes
      mellitus, worsening of renal function (reduction in estimated glomerular
      filtration rate), and baseline and increases in N-terminal pro-brain natriuretic
      peptide concentrations. Increases in hs-cTnT concentrations were associated with
      all-cause mortality (incidence rates, 8.19 [7.51-8.88] and 6.79 [5.98-7.61] per
      100 person-years in Val-HeFT and GISSI-HF, respectively, with hazard ratios [95%
      confidence intervals] of 1.59 [1.39-1.82] and 1.88 [1.50-2.35]) after adjustment
      for conventional risk factors and baseline levels of hs-cTnT and N-terminal pro
      brain natriuretic peptide. Changes in hs-cTnT concentration modestly improved
      prognostic discrimination beyond baseline values for fatal outcomes only.
      CONCLUSIONS: Despite very low circulating concentrations, changes in hs-cTnT
      concentrations over time are robust predictors of future cardiovascular events in
      patients with chronic HF but add limited prognostic discrimination. CLINICAL
      TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier:
      NCT00336336.

PMID- 22139752
TI  - [Implant supported anterior crowns customized by computer-aided design. State of
      the technique and case report].

PMID- 22139753
TI  - Influence of moisture on the availability and persistence of clotrimazole and
      fluconazole in sludge-amended soil.
AB  - Applying sewage sludge to soil is a common practice in many parts of the world.
      Thus, pharmaceutical compounds, such as azoles, can be released into the
      environment after sludge is applied to soil. To understand the fate of
      clotrimazole and fluconazole (pharmaceuticals used as antifungals in humans) in
      soil after its amendment with sludge, a reliable and sensitive method has been
      developed to determine these compounds in the solid and aqueous phases of soil.
      Desorption of clotrimazole from soil amended with sludge was negligible, whereas
      a rapid desorption of fluconazole was observed. Dissipation rates of these azoles
      were determined in amended soil incubated at 25 degrees C with moisture contents
      ranging from 4.5 to 20%. Clotrimazole was more persistent than fluconazole in dry
      soil, whereas the contrary occurred in wet soil. Partitioning soil:soil solution
      of these azoles varied with time and moisture contents. Clotrimazole was found in
      soil with negligible amounts in soil solution, whereas fluconazole was
      approximately partitioned 50:50 during the assay time (60 d) at any soil moisture
      content. Occasional rainfall coupled with a relatively low binding soil capacity
      can result in the contamination of surface and groundwaters by fluconazole,
      whereas clotrimazole will remain in the soil.

PMID- 22139754
TI  - Degradable polymers may improve dental practice.
AB  - The use of biomaterials in dentistry is more widespread than in any other medical
      field in terms of both amount and variety. Most of them were not originally
      designed for dental applications but for other medical applications or,
      sometimes, for no medical purposes. Among these materials, biodegradable
      materials play an important role, especially in bone regeneration and in
      periodontal surgery. This paper briefly reviews some degradable polymers
      developed as tools for the treatment of periodontal and bone diseases. We discuss
      materials previously applied in other industrials contexts, such as polyesters,
      methylcellulose, and chitosan and we provide perspectives for their use in
      periodontal regeneration.

PMID- 22139755
TI  - Finite element 3D modeling of mechanical behavior of mineralized collagen
      microfibrils.
AB  - PURPOSE: The aim of this work is to develop a 3D finite elements model to study
      the nanomechanical behavior of mineralized collagen microfibrils, which consists
      of three phases, (i) collagen phase formed by five tropocollagen (TC) molecules
      linked together with cross-links, (ii) a mineral phase (Hydroxyapatite), and
      (iii) impure mineral phase, and to investigate the important role of individual
      properties of every constituent. METHODS: The mechanical and geometric properties
      (TC molecule diameter) of both tropocollagen and mineral were taken into
      consideration as well as cross-links, which was represented by spring elements
      with adjusted properties based on experimental data. In this paper an equivalent
      homogenized model was developed to assess the whole microfibril mechanical
      properties (Young's modulus and Poisson's ratio) under varying mechanical
      properties of each phase. RESULTS: In this study, both equivalent Young's modulus
      and Poisson's ratio, which were expressed as functions of Young's modulus of each
      phase, were obtained under tensile load with symmetric and periodic boundary
      conditions.

PMID- 22139756
TI  - Assessment of scaffold porosity: the new route of micro-CT.
AB  - A complete morphologic characterization of porous scaffolds for tissue
      engineering application is fundamental, as the architectural parameters, in
      particular porosity, strongly affect the mechanical and biological performance of
      the structures. Therefore, appropriate techniques for this purpose need to be
      selected. Several techniques for the assessment of scaffold porosity have been
      proposed, including Scanning Electron Microscopy observation, mercury and liquid
      extrusion porosimetry, gas pycnometry, and capillary flow porometry. Each of
      these techniques has several drawbacks and, a combination of different techniques
      is often required so as to achieve an in depth study of the morphologic
      properties of the scaffold. A single technique is often limited and suitable only
      for the assessment of a specific parameter. To overcome this limit, the most
      attractive option would be a single nondestructive technique, yet capable of
      providing a comprehensive set of data. It appears that micro-computed tomography
      (micro-CT) can potentially fulfill this role. Initially developed to characterize
      the 3D trabecular microarchitecture of bone, its use has been recently exploited
      by researchers for the morphologic characterization of porous biomaterials, as it
      enables obtaining a full assessment of the porous structures both in terms of
      pore size and interconnected porosity. This review aims to explore the use of
      micro-CT in scaffold characterization, comparing it with other previously
      developed techniques; we also focus on the contribution of this innovative tool
      to the development of scaffold-based tissue engineering application.

PMID- 22139757
TI  - Sebacic and succinic acid derived plasticised PVC for the inhibition of
      biofouling in its initial stages.
AB  - AIM: In this work, we report the use of plasticized poly vinylchloride (PVC) as a
      potential antifouling coating material. The materials contain a variety of
      sebacic and succinic acid-derived plasticisers providing a variation in molecular
      shape and structure; diethyl succinate (DESn), di-(2-ethylhexyl sebacate) (DEHS),
      dibutyl sebacate (DBS), and diethyl sebacate (DES). Each plasticiser from the
      sebacate group possessed the same basic C10H16O4 moiety with varied dialkyl
      terminated groups, affording a different range of homologous series plasticisers.
      This work investigates whether branching of the side substituted alkyl chains on
      each plasticiser molecule affects microorganism attachment and subsequent
      fouling. MATERIALS AND METHODS: The plasticized polymers are spin coated to
      create thin films for testing. In order to determine the antifouling capacity of
      the materials, the polymer coatings underwent a series of analyses for biomass
      determination, glycocalyx production, and protein and carbohydrate adsorption.
      Topological and morphological characterization was performed using scanning
      electron microscopy (SEM) and atomic force microscopy (AFM). RESULTS: After a 7
      day laboratory biofouling study it was found that the plasticisers with increased
      alkyl branching, DESN, and DEHS revealed the greatest degree of prevention of
      microorganism colonization and attachment thus significantly reducing the initial
      formation of biofilms by up to 65% in some biofouling assays when compared to the
      uPVC blank.

PMID- 22139758
TI  - Usefulness of dual-energy CT scanning at 80 kVp for identifying hilar and
      mediastinal structures: evaluation of contrast enhancement of the pulmonary
      vessels and lymph nodes.
AB  - PURPOSE: We examined whether the 80-kVp CT images scanned at 100 s after contrast
      material injection using a dual-source scanner could be substituted for the
      conventional 120-kVp images obtained at an earlier timing of 30 s. MATERIALS AND
      METHODS: Seventy-eight patients with suspected lung cancer were examined with a
      120-kVp mode at 30 s after contrast material injection (early phase) and a dual
      energy (80 and 140 kVp) mode at 100 s (late phase). CT numbers of the pulmonary
      artery (PA), pulmonary vein (PV) and hilar zone lymph nodes (LN) were measured.
      Contrast between the PA/PV and LN was visually evaluated using a 5-point scale.
      Beam-hardening artifacts were also visually assessed. RESULTS: The mean
      difference in attenuation between the PA/PV and LN on the early phase 120-kVp,
      late phase 80-kVp and late phase weighted-average 120-kVp images was 171.3/160.8,
      100.5/106.8 and 67.5/67.5, respectively (p < 0.001). The mean contrast score of
      these three images for the hilar/mediastinal LN was 4.5/4.7, 3.4/3.8 and 2.9/3.3,
      respectively (all p < 0.05). The mean artifact score of the three images was 2.6,
      4.0 and 4.0, respectively; on most early phase images, the beam-hardening
      artifacts influenced the diagnosis (p < 0.001). CONCLUSION: The late phase 80-kVp
      images showing few artifacts may be an alternative to early phase 120-kVp images.

PMID- 22139759
TI  - Arterial blood supply to the caudate lobe of the liver from the proximal branches
      of the right inferior phrenic artery in patients with recurrent hepatocellular
      carcinoma after chemoembolization.
AB  - PURPOSE: To evaluate the arterial blood supply to the caudate lobe of the liver
      from the proximal branches of the right inferior phrenic artery (RIPA) in
      patients with recurrent hepatocellular carcinoma after transcatheter arterial
      chemoembolization (TACE). MATERIALS AND METHODS: Thirteen patients, including 10
      who had a history of TACE of the caudate artery (A1), underwent TACE of the
      proximal RIPA branches. Iodized oil distribution was evaluated by computed
      tomography (CT) 1-week after TACE. Angiographic findings were also evaluated.
      RESULTS: Previously embolized A1 was occluded (n = 15) or attenuated (n = 2). In
      one of three patients without A1 TACE, A1 was also attenuated. TACE was performed
      at the first branch of the proximal RIPA (n = 8), the first branch of the
      anterior branch (n = 6), and the first branch of the posterior branch (n = 1),
      respectively. Iodized oil was mainly distributed into the dorsal part of the
      Siegel lobe (SP) (n = 10), the caudate process (n = 1), and both (n = 2). In
      three of seven patients who had undergone serial RIPA angiography, RIPA
      parasitization to SP was suspected before A1 TACE. CONCLUSION: The proximal RIPA
      branches mainly supply the SP when A1 is attenuated.

PMID- 22139760
TI  - Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus
      amplification in ovarian clear cell carcinoma.
AB  - BACKGROUND: The goal of this study was to examine the clinical significance of
      ZNF217 amplification and assess whether ZNF217 could be a potential therapeutic
      target in ovarian clear cell carcinoma (OCCC). METHODS: ZNF217 expression and
      amplification in OCCC was assessed by immunohistochemistry, fluorescence in situ
      hybridization, and clinical data collected via a retrospective chart review.
      ZNF217 gene knockdown using silencing RNA (siRNA) was used to assess ZNF217
      functions in OCCC cell lines. RESULTS: Gene amplification was identified in 12 of
      60 (20.0%) OCCCs. ZNF217 copy number correlated significantly with ZNF217 protein
      expression (r = 0.341; P<.01). ZNF217 amplification correlated significantly with
      shorter progression-free (P = .0042) and overall (P = .0199) survival. There were
      nonsignificant trends between high ZNF217 protein expression and poor progression
      free (P = .2594) and overall (P = .2199) survival. Multivariate analysis revealed
      ZNF217 gene amplification to be an independent prognostic factor for progression
      free and overall survival after standard platinum agent-based chemotherapy (P =
      .0339 and P = .031, respectively). Profound growth inhibition and apoptosis were
      observed in ZNF217 siRNA-treated cancer cells with gene amplification compared
      with cancer cells with ZNF217 moderate expression without ZNF217 gene
      amplification or with low ZNF217 expression. CONCLUSION: These findings indicate
      that ZNF217 overexpression is critical to growth and survival of OCCCs with
      ZNF217 gene amplification. Furthermore, they suggest that ZNF217 siRNA-induced
      phenotypes depend on amplification status of OCCCs. Therefore, ZNF217-targeted
      therapy may benefit OCCC patients with ZNF217 amplification.

PMID- 22139761
TI  - Libby vermiculite exposure and risk of developing asbestos-related lung and
      pleural diseases.
AB  - PURPOSE OF REVIEW: The vermiculite ore formerly mined in Libby, Montana, contains
      asbestiform amphibole fibers of winchite, richterite, and tremolite asbestos.
      Because of the public health impact of widespread occupational and
      nonoccupational exposure to amphiboles in Libby vermiculite, numerous related
      studies have been published in recent years. Here we review current research
      related to this issue. RECENT FINDINGS: Excess morbidity and mortality
      classically associated with asbestos exposure have been well documented among
      persons exposed to Libby vermiculite. Excess morbidity and mortality have
      likewise been documented among persons with only nonoccupational exposure. A
      strong exposure-response relationship exists for many malignant and nonmalignant
      outcomes and the most common outcome, pleural plaques, may occur at low lifetime
      cumulative exposures. SUMMARY: The public health situation related to Libby,
      Montana, has led to huge investments in public health actions and research. The
      resulting studies have added much to the body of knowledge concerning health
      effects of exposures to Libby amphibole fibers specifically and asbestos exposure
      in general.

PMID- 22139762
TI  - The orientation of the tympanic membrane.

PMID- 22139763
TI  - Parametric and non-parametric confidence intervals of the probability of
      identifying early disease stage given sensitivity to full disease and specificity
      with three ordinal diagnostic groups.
AB  - In practice, there exist many disease processes with three ordinal disease
      classes, that is, the non-diseased stage, the early disease stage, and the fully
      diseased stage. Because early disease stage is likely the best time window for
      treatment interventions, it is important to have diagnostic tests that have good
      diagnostic ability to discriminate the early disease stage from the other two
      stages. In this paper, we present both parametric and non-parametric approaches
      for confidence interval estimation of probability of detecting early disease
      stage given the true classification rates for non-diseased group and diseased
      group, namely, the specificity and the sensitivity to full disease. We analyze a
      data set on the clinical diagnosis of early-stage Alzheimer's disease from the
      neuropsychological database at the Washington University Alzheimer's Disease
      Research Center using the proposed approaches.

PMID- 22139765
TI  - Steps to pluripotent learning: provocative teaching.
AB  - Education involves interactions between students and teachers in a societal
      framework. Teachers can best serve their students and society by making students
      flexible enough to thrive under uncertain conditions. They should, in a sense,
      nourish, nurture, provoke, and stimulate pluripotent "educatoblasts."

PMID- 22139764
TI  - Comparison of relative cerebral blood flow maps using pseudo-continuous arterial
      spin labeling and single photon emission computed tomography.
AB  - Pseudo-continuous arterial spin labeling (PCASL) MRI is a relatively new arterial
      spin labeling technique and has the potential to extend the cerebral blood flow
      (CBF) measurement to all tissue types, including white matter. However, the
      arterial transit time (delta(a)) for white matter is not well established and a
      limited number of reports using multi-delay methods have yielded inconsistent
      findings. In this study, we used a different approach and measured white matter
      delta(a) (mean +/- standard deviation, 1541 +/- 173  ms) by determining the
      arrival times of exogenous contrast agent in a bolus tracking experiment. The
      data also confirmed delta(a) of gray matter to be 912 +/- 209  ms. In the second
      part of this study, we used these parameters in PCASL kinetic models and compared
      relative CBF (rCBF, with respect to the whole brain) maps with those measured
      using a single photon emission computed tomography (SPECT) technique. It was
      found that the use of tissue-specific delta(a) in the PCASL model was helpful in
      improving the correspondence between the two modalities. On a regional level, the
      gray/white matter CBF ratios were 2.47 +/- 0.39 and 2.44 +/- 0.18 for PCASL and
      SPECT, respectively. On a single-voxel level, the variance between the modalities
      was still considerable, with an average rCBF difference of 0.27.

PMID- 22139766
TI  - Teaching fluid shifts during orthostasis using a classic paper by Foux et al.
AB  - Hypovolemic and orthostatic challenge can be simulated in humans by the
      application of lower body negative pressure (LBNP), because this perturbation
      leads to peripheral blood pooling and, consequently, central hypovolemia. The
      classic paper by Foux and colleagues clearly shows the effects of orthostasis
      simulated by LBNP on fluid shifts and homeostatic mechanisms. The carefully
      carried out experiments reported in this paper show the interplay between
      different physiological control systems to ensure blood pressure regulation,
      failure of which could lead to critical decreases in cerebral blood flow and
      syncope. Here, a teaching seminar for graduate students is described that is
      designed in the context of this paper and aimed at allowing students to learn how
      Foux and colleagues have advanced this field by addressing important aspects of
      blood regulation. This seminar is also designed to put their research into
      perspective by including important components of LBNP testing and protocols
      developed in subsequent research in the field. Learning about comprehensive
      protocols and carefully controlled studies can reduce confounding variables and
      allow for an optimal analysis and elucidation of the physiological responses that
      are being investigated. Finally, in collaboration with researchers in
      mathematical modeling, in the future, we will incorporate the concepts of
      applicable mathematical models into our curriculum.

PMID- 22139767
TI  - The core principles ("big ideas") of physiology: results of faculty surveys.
AB  - Physiology faculty members at a wide range of institutions (2-yr colleges to
      medical schools) were surveyed to determine what core principles of physiology
      they want their students to understand. From the results of the first survey, 15
      core principles were described. In a second survey, respondents were asked to
      rank order these 15 core principles and, independently, to identify the three
      most important for their students to understand. The five most important core
      principles were "cell membrane," "homeostasis," "cell-to-cell communications,"
      "interdependence," and "flow down gradients." We then "unpacked" the flow down
      gradients core principle into the component ideas of which it is comprised. This
      unpacking was sent to respondents who were asked to identify the importance of
      each of the component ideas. Respondents strongly agreed with the importance of
      the component ideas we had identified. We will be using the responses to our
      surveys as we begin the development of a conceptual assessment of physiology
      instrument (i.e., a concept inventory).

PMID- 22139768
TI  - Origin, utilization, and recycling of nucleosides in the central nervous system.
AB  - The brain relies on the salvage of preformed purine and pyrimidine rings, mainly
      in the form of nucleosides, to maintain its nucleotide pool in the proper
      qualitative and quantitative balance. The transport of nucleosides from blood
      into neurons and glia is considered to be an essential prerequisite to enter
      their metabolic utilization in the brain. Recent lines of evidence have also
      suggested that local extracellular nucleoside triphosphate (NTP) degradation may
      contribute to brain nucleosides. Plasma membrane-located ectonucleotidases, with
      their active sites oriented toward the extracellular space, catalyze the
      successive hydrolysis of NTPs to their respective nucleosides. Apart from the
      well-established modulation of ATP, ADP, adenosine (the purinergic agonists),
      UTP, and UDP (the pyrimidinergic agonists) availability at their respective
      receptors, ectonucleotidases may also serve the local reutilization of
      nucleosides in the brain. After their production in the extracellular space by
      the ectonucleotidase system, nucleosides are transported into neurons and glia
      and converted back to NTPs via a set of purine and pyrimidine salvage enzymes.
      Finally, nucleotides are transported into brain cell vescicles or granules and
      released back into the extracellular space. The key teaching concepts to be
      included in a two-to three-lecture block on the molecular mechanisms of the local
      nucleoside recycling process, based on a cross talk between the brain
      extracellular space and cytosol, are discussed in this article.

PMID- 22139769
TI  - Explorations in statistics: regression.
AB  - Learning about statistics is a lot like learning about science: the learning is
      more meaningful if you can actively explore. This seventh installment of
      Explorations in Statistics explores regression, a technique that estimates the
      nature of the relationship between two things for which we may only surmise a
      mechanistic or predictive connection. Regression helps us answer three questions:
      does some variable Y depend on another variable X; if so, what is the nature of
      the relationship between Y and X; and for some value of X, what value of Y do we
      predict? Residual plots are an essential component of a thorough regression
      analysis: they help us decide if our statistical regression model of the
      relationship between Y and X is appropriate.

PMID- 22139771
TI  - Statistics, probability, significance, likelihood: words mean what we define them
      to mean.

PMID- 22139772
TI  - Presenting data: can you follow a recipe?

PMID- 22139770
TI  - United States Army Research Institute of Environmental Medicine: Warfighter
      research focusing on the past 25 years.
AB  - The United States Army Research Institute of Environmental Medicine (USARIEM)
      celebrated its 50th anniversary on July 1, 2011. This article reviews its
      history, evolution, and transition of its research programs as well as its
      scientific and military accomplishments, emphasizing the past 25 yr. During the
      1990s, USARIEM published a series of pocket guides providing guidance for
      sustaining Warfighter health and performance in Southwest Asia, Somalia, the
      former Republic of Yugoslavia, Rwanda, and Haiti. Issues identified during
      Operation Desert Storm elicited research that improved nutritional guidelines for
      protracted desert operations; safer use of nuclear, chemical, and biological
      protective clothing; equipment, development, and fielding of efficient
      microclimate cooling systems; and effective evaluation of pharmaceuticals to
      protect soldiers from chemical and biological threats. During the first decade of
      the 21st century, USARIEM and the Department of the Army published official
      medical/performance doctrines for operations in the heat and cold and at high
      altitude. The current Global War on Terrorism focused research to improve
      doctrines for hot, cold, and high-altitude operations, reduce musculoskeletal
      training injuries, provide improved field nutrition, more efficient planning for
      operational water requirements, and improve both military clothing and materiel.
      This article also describes the critically important interactions and
      communications between USARIEM and deployed units and the benefits to Warfighters
      from this association. This report presents USARIEM's unique and world-class
      facilities, organizational changes, scientific and support personnel, and major
      research accomplishments, including the publication of 2,200 scientific papers
      over the past 25 yr.

PMID- 22139773
TI  - Integrating an open-source course management system (Moodle) into the teaching of
      a first-year medical physiology course: a case study.
AB  - Educators in medical schools around the world are presently experimenting with
      innovative ways of using web-based learning to supplement the existing teaching
      and learning process. We have recently used a popular open-source course
      management system (CMS) called the modular object-oriented dynamic learning
      environment (Moodle) to construct an online site (DPhysiol) to facilitate our
      face-to-face teaching of physiology to a group of first-year students in the
      Bachelor of Medicine and Bachelor of Surgery program. The integration of the
      Moodle site into our teaching was assessed using online log activity, student
      examination marks, and feedback from students. The freely available Moodle
      platform was simple to use, helped to effectively deliver course materials, and
      has features that allowed cooperative learning. Students who used the CMS
      throughout their academic year and commented favorably regarding its use as a
      complement to the face-to-face classroom sessions. The group of students used the
      CMS obtained significantly higher scores in the final examination compared with
      the previous class that did not use the CMS. In addition, there was a significant
      correlation between student participation and performance in online quizzes and
      their final examination marks. However, students' overall online usage of the CMS
      did not correlate with their examination marks. We recommend Moodle as a useful
      tool for physiology educators who are interested in integrating web-based
      learning into their existing teaching curriculum.

PMID- 22139774
TI  - Effect of selected "desirable difficulty" learning strategies on the retention of
      physiology information.
AB  - The purpose of this study was to examine the effects of interleaving and
      expanding retrieval on the retention of physiology concepts. Participants (n =
      189) read and then reread 30 immunology and reproductive physiology passages.
      Half of the participants read and then reread the passages in a blocked manner
      (e.g., a(1)a(2)a(3)b(1)b(2)b(3)), and the other half did so in an interleaved
      manner (e.g., a(1)b(1)b(2)a(2)a(3)b(3)). Participants were then repeatedly
      assessed, without feedback, after either a uniform or an expanding series of
      intervals. Half of the students from both the blocked and interleaved groups
      completed the assessments 1, 2, and 3 days after rereading the passages
      (uniform), whereas the other half completed the assessments immediately and 1 and
      3 days after rereading the passages (expanding). All participants completed a
      final assessment 10 days after rereading the passages. There were no significant
      differences between the blocked and interleaved groups on any of the assessments,
      nor were there any significant interactions between the groups on any of the
      assessments. Those in the expanding retrieval group scored significantly higher
      than those in the uniform group on all four assessments (ANOVA; assessment 1: F =
      35.12, P = 0.00; assessment 2: F = 13.88, P = 0.00; assessment 3: F = 10.87, P =
      0.00; and assessment 4: F = 6.79, P = 0.01). Mean final assessment scores were
      47.58 +/- 19.81 and 40.50 +/- 17.17 for the expanding and uniform groups,
      respectively. The results indicate that participants benefited more from
      expanding retrieval practice.

PMID- 22139775
TI  - Why flies? Inexpensive public engagement exercises to explain the value of basic
      biomedical research on Drosophila melanogaster.
AB  - Invertebrate model organisms are powerful systems for uncovering conserved
      principles of animal biology. Despite widespread use in scientific communities,
      invertebrate research is often severely undervalued by laypeople. Here, we
      present a set of simple, inexpensive public outreach exercises aimed at
      explaining to the public why basic research on one particular invertebrate, the
      insect Drosophila melanogaster, is valuable. First, we designed seven teaching
      modules that highlight cutting-edge research in Drosophila genetics, metabolism,
      physiology, and behavior. We then implemented these exercises in a public
      outreach event that included both children and adults. Quantitative evaluation of
      participant feedback suggests that these exercises 1) teach principles of animal
      biology, 2) help laypeople better understand why researchers study fruit flies,
      and 3) are effective over a wide range of age groups. Overall, this work provides
      a blueprint for how to use Drosophila as a vehicle for increasing public
      awareness and appreciation of basic research on genetically tractable insects in
      particular and invertebrates in general.

PMID- 22139776
TI  - Exploring first-year undergraduate medical students' self-directed learning
      readiness to physiology.
AB  - Medical students are expected to possess self-directed learning skills to pursue
      lifelong learning. Previous studies have reported that the readiness for self
      directed learning depends on personal attributes as well as the curriculum
      followed in institutions. Melaka Manipal Medical College of Manipal University
      (Karnataka, India) offers a Bachelor of Medicine and Bachelor of Surgery (MBBS)
      twinning program that is of 5 yr in duration. Keeping in mind the amount of time
      that the curriculum has devoted for self-directed learning, we explored the self
      directed learning readiness of first-year MBBS students (n = 130) using a self
      directed learning readiness scale (SDLRS) and explored the correlation between
      SDLRS scores of high achievers, medium achievers, and low achievers with their
      academic performance in physiology examinations. Students were requested to
      respond to each item of the SDLRS on a Likert scale. Median scores of the three
      scales of the SDLRS were compared across the three groups of students using a
      Kruskall-Wallis test. SDLRS scores of the students (n = 130) were correlated with
      their marks in theory papers of first, second, and third block-end examinations
      using Spearmann's correlation coefficient. The mean item score for desire for
      learning was found to be higher followed by self-control and self-management.
      Data analyses showed significantly high (P < 0.03) median scores for self-control
      for high achievers compared with medium and low achievers. Between the groups,
      high achievers had a higher score for all the three scales of the SDLRS followed
      by low and medium achievers. SDLRS scores and academic performance of the three
      groups of students were found to exhibit a weak correlation. This study threw
      light on the fact that despite having a high desire for learning and ability of
      self-control, students need to be supported in their self-management skills.

PMID- 22139777
TI  - Are faculty predictions or item taxonomies useful for estimating the outcome of
      multiple-choice examinations?
AB  - The purpose of this study was to evaluate whether multiple-choice item difficulty
      could be predicted either by a subjective judgment by the question author or by
      applying a learning taxonomy to the items. Eight physiology faculty members
      teaching an upper-level undergraduate human physiology course consented to
      participate in the study. The faculty members annotated questions before exams
      with the descriptors "easy," "moderate," or "hard" and classified them according
      to whether they tested knowledge, comprehension, or application. Overall analysis
      showed a statistically significant, but relatively low, correlation between the
      intended item difficulty and actual student scores (rho = -0.19, P < 0.01),
      indicating that, as intended item difficulty increased, the resulting student
      scores on items tended to decrease. Although this expected inverse relationship
      was detected, faculty members were correct only 48% of the time when estimating
      difficulty. There was also significant individual variation among faculty members
      in the ability to predict item difficulty (chi(2) = 16.84, P = 0.02). With regard
      to the cognitive level of items, no significant correlation was found between the
      item cognitive level and either actual student scores (rho = -0.09, P = 0.14) or
      item discrimination (rho = 0.05, P = 0.42). Despite the inability of faculty
      members to accurately predict item difficulty, the examinations were of high
      quality, as evidenced by reliability coefficients (Cronbach's alpha) of 0.70
      0.92, the rejection of only 4 of 300 items in the postexamination review, and a
      mean item discrimination (point biserial) of 0.37. In conclusion, the effort of
      assigning annotations describing intended difficulty and cognitive levels to
      multiple-choice items is of doubtful value in terms of controlling examination
      difficulty. However, we also report that the process of annotating questions may
      enhance examination validity and can reveal aspects of the hidden curriculum.

PMID- 22139778
TI  - Enhancing learning through optimal sequencing of web-based and manikin simulators
      to teach shock physiology in the medical curriculum.
AB  - The Association of American Medical Colleges has encouraged educators to
      investigate proper linkage of simulation experiences with medical curricula. The
      authors aimed to determine if student knowledge and satisfaction differ between
      participation in web-based and manikin simulations for learning shock physiology
      and treatment and to determine if a specific training sequencing had a
      differential effect on learning. All 40 second-year medical students participated
      in a randomized, counterbalanced study with two interventions: group 1 (n = 20)
      participated in a web-based simulation followed by a manikin simulation and group
      2 (n = 20) participated in reverse order. Knowledge and attitudes were
      documented. Mixed-model ANOVA indicated a significant main effect of time
      (F(1,38) = 18.6, P < 0.001, eta(p)(2) = 0.33). Group 1 scored significantly
      higher on quiz 2 (81.5%) than on quiz 1 (74.3%, t(19) = 3.9, P = 0.001), for an
      observed difference of 7.2% (95% confidence interval: 3.3, 11.0). Mean quiz
      scores of group 2 did not differ significantly (quiz 1: 77.0% and quiz 2: 79.7%).
      There was no significant main effect of group or a group by time interaction
      effect. Students rated the simulations as equally effective in teaching shock
      physiology (P = 0.88); however, the manikin simulation was regarded as more
      effective in teaching shock treatment (P < 0.001). Most students (73.7%)
      preferred the manikin simulation. The two simulations may be of similar efficacy
      for educating students on the physiology of shock; however, the data suggest
      improved learning when web-based simulation precedes manikin use. This finding
      warrants further study.

PMID- 22139780
TI  - Does sex (female versus male) influence the impact of class attendance on
      examination performance?
AB  - The "conventional wisdom" is that grades are related to class attendance, i.e.,
      students who attend classes more frequently obtain better grades and class
      attendance dramatically contributes to enhanced learning. However, the influence
      of sex (female vs. male) on this relationship is understudied. Furthermore, there
      have been several studies examining the impact of attendance on course grades
      that challenge the conventional wisdom. To address these issues, we determined
      the effect of class attendance on examination scores for female and male students
      enrolled in our undergraduate exercise physiology class of 51 students (20 female
      students and 31 male students). The experiment was designed not to interfere with
      the normal conduct of the course. Attendance was recorded in each class, and,
      although regular attendance was encouraged, it was not required and did not
      factor into the final grades. The final grade reflected the average days of
      attendance for female students only. Specifically, female students earning a
      grade above the class average attended 89 +/- 4% of the classes; however, female
      students earning a grade below the class average attended only 64 +/- 6% of the
      classes. In sharp contrast, there was no difference in the number of classes
      attended for male students earning grades above or below the class average (84 +/
      3% vs. 79 +/- 5%). Accordingly, some male students were absent frequently but
      scored above the class average, whereas other male students attended many classes
      but scored below the class average. Thus, the influence of regular attendance on
      examination performance is more important for female students than male students.

PMID- 22139779
TI  - Impact of problem-based learning in a large classroom setting: student perception
      and problem-solving skills.
AB  - Problem-based learning (PBL) can be described as a learning environment where the
      problem drives the learning. This technique usually involves learning in small
      groups, which are supervised by tutors. It is becoming evident that PBL in a
      small-group setting has a robust positive effect on student learning and skills,
      including better problem-solving skills and an increase in overall motivation.
      However, very little research has been done on the educational benefits of PBL in
      a large classroom setting. Here, we describe a PBL approach (using tutorless
      groups) that was introduced as a supplement to standard didactic lectures in
      University of British Columbia Okanagan undergraduate biochemistry classes
      consisting of 45-85 students. PBL was chosen as an effective method to assist
      students in learning biochemical and physiological processes. By monitoring
      student attendance and using informal and formal surveys, we demonstrated that
      PBL has a significant positive impact on student motivation to attend and
      participate in the course work. Student responses indicated that PBL is superior
      to traditional lecture format with regard to the understanding of course content
      and retention of information. We also demonstrated that student problem-solving
      skills are significantly improved, but additional controlled studies are needed
      to determine how much PBL exercises contribute to this improvement. These
      preliminary data indicated several positive outcomes of using PBL in a large
      classroom setting, although further studies aimed at assessing student learning
      are needed to further justify implementation of this technique in courses
      delivered to large undergraduate classes.

PMID- 22139781
TI  - Development of a model for whole brain learning of physiology.
AB  - In this report, a model was developed for whole brain learning based on Curry's
      onion model. Curry described the effect of personality traits as the inner layer
      of learning, information-processing styles as the middle layer of learning, and
      environmental and instructional preferences as the outer layer of learning. The
      model that was developed elaborates on these layers by relating the personality
      traits central to learning to the different quadrants of brain preference, as
      described by Neethling's brain profile, as the inner layer of the onion. This
      layer is encircled by the learning styles that describe different information
      processing preferences for each brain quadrant. For the middle layer, the
      different stages of Kolb's learning cycle are classified into the four brain
      quadrants associated with the different brain processing strategies within the
      information processing circle. Each of the stages of Kolb's learning cycle is
      also associated with a specific cognitive learning strategy. These two inner
      circles are enclosed by the circle representing the role of the environment and
      instruction on learning. It relates environmental factors that affect learning
      and distinguishes between face-to-face and technology-assisted learning. This
      model informs on the design of instructional interventions for physiology to
      encourage whole brain learning.

PMID- 22139782
TI  - Teaching cardiac electrophysiology modeling to undergraduate students: laboratory
      exercises and GPU programming for the study of arrhythmias and spiral wave
      dynamics.
AB  - As part of a 3-wk intersession workshop funded by a National Science Foundation
      Expeditions in Computing award, 15 undergraduate students from the City
      University of New York(1) collaborated on a study aimed at characterizing the
      voltage dynamics and arrhythmogenic behavior of cardiac cells for a broad range
      of physiologically relevant conditions using an in silico model. The primary goal
      of the workshop was to cultivate student interest in computational modeling and
      analysis of complex systems by introducing them through lectures and laboratory
      activities to current research in cardiac modeling and by engaging them in a
      hands-on research experience. The success of the workshop lay in the exposure of
      the students to active researchers and experts in their fields, the use of hands
      on activities to communicate important concepts, active engagement of the
      students in research, and explanations of the significance of results as the
      students generated them. The workshop content addressed how spiral waves of
      electrical activity are initiated in the heart and how different parameter values
      affect the dynamics of these reentrant waves. Spiral waves are clinically
      associated with tachycardia, when the waves remain stable, and with fibrillation,
      when the waves exhibit breakup. All in silico experiments were conducted by
      simulating a mathematical model of cardiac cells on graphics processing units
      instead of the standard central processing units of desktop computers. This
      approach decreased the run time for each simulation to almost real time, thereby
      allowing the students to quickly analyze and characterize the simulated
      arrhythmias. Results from these simulations, as well as some of the background
      and methodology taught during the workshop, is presented in this article along
      with the programming code and the explanations of simulation results in an effort
      to allow other teachers and students to perform their own demonstrations,
      simulations, and studies.

PMID- 22139783
TI  - A double-blind atropine trial for active learning of autonomic function.
AB  - Here, we describe a human physiology laboratory class measuring changes in
      autonomic function over time in response to atropine. Students use themselves as
      subjects, generating ownership and self-interest in the learning as well as
      directly experiencing the active link between physiology and pharmacology in
      people. The class is designed to concomitantly convey the importance of bias in
      experimentation by adopting a double-blind placebo-controlled approach. We have
      used this class effectively in various forms with ~600 students receiving
      atropine over the last 16 yr. This class has received favorable feedback from
      staff and students of medicine, pharmacy, and neuroscience, and we recommend it
      for such undergraduates. The learning objectives that students are expected to
      achieve are to be able to 1) know the ethical, safety, and hygiene requirements
      for using human volunteers as subjects; 2) implement and explain a double-blind
      placebo-controlled trial; 3) design, agree, and execute a protocol for making
      (and accurately recording) precise reproducible measurements of pulse rate, pupil
      diameter, and salivary flow; 4) evaluate the importance of predose periods and
      measurement consistency to detect effects (including any reversibility) after an
      intervention; 5) experience direct cause-and-effect relationships integrating
      physiology with pharmacology in people; 6) calculate appropriate summary
      statistics to describe the data and determine the data's statistical
      significance; 7) recognize normal variability both within and between subjects in
      baseline physiological parameters and also recognize normal variability in
      response to pharmacological treatment; 8) infer the distribution and role of
      muscarinic receptors in the autonomic nervous system with respect to the heart,
      eye, and mouth; 9) identify and explain the clinical significance of differences
      in effect due to the route and formulation of atropine; 10) produce and deliver a
      concise oral presentation of experimental findings; and 11) produce a written
      report in the form of a short scientific research article. The results of a
      typical study are presented, which demonstrate that the administration of
      atropine by a subcutaneous injection elicited a significant increase in pulse
      rate and pupil diameter and a significant decrease in salivary flow, whereas
      administration of atropine in an oral liquid elicited significant effects on
      pulse rate and salivary flow, and an oral solid format elicited a significant
      alteration in salivary flow alone. More detailed analysis of the salivary flow
      data demonstrated clear differences between the routes of administration and
      formulation in the onset and magnitude of action of atropine.

PMID- 22139785
TI  - Using Willie's acid-base box for blood gas analysis.

PMID- 22139784
TI  - Visualizing and quantifying the suppressive effects of glucocorticoids on the
      tadpole immune system in vivo.
AB  - A challenging topic in undergraduate physiology courses is the complex
      interaction between the vertebrate endocrine system and the immune system. There
      are relatively few established and accessible laboratory exercises available to
      instructors to help their students gain a working understanding of these
      interactions. The present laboratory module was developed to show students how
      glucocorticoid receptor activity can be pharmacologically modulated in Xenopus
      laevis tadpoles and the resulting effects on thymus gland size visualized and
      quantified in vivo. After treating young tadpoles with a cortisol receptor
      agonist (dexamethasone) for 1 wk, students can easily visualize the suppressive
      effects of glucocorticoids on the intact thymus gland, which shrinks dramatically
      in size in response to this steroid hormone analog. However, the suppressive
      effect of dexamethasone is nullified in the presence of the glucocorticoid
      receptor antagonist RU-486, which powerfully illustrates the specific effects of
      glucocorticoid receptor inhibition on the immune system. Image analysis and
      statistics software are used to quantify the effects of glucocorticoid modulation
      on thymus size.

PMID- 22139786
TI  - Active learning in a large medical classroom setting for teaching renal
      physiology.

PMID- 22139787
TI  - A model for collaborative laboratory experiences between higher education and a
      high school technical preparation program: promoting higher education, mentoring,
      and research.

PMID- 22139788
TI  - Designing an interactive activity to integrate animal physiology in the context
      of different disciplines.

PMID- 22139789
TI  - Transcription factor Runx2 and its application to bone tissue engineering.
AB  - Cbfa1/Runx2 is a bone transcription factor homologous to the Drosophila protein,
      Runt. Runx2 is a master gene that encodes for a protein involved in the
      osteogenic differentiation process from mesenchymal precursors. It is known that
      in Cbfa1 deficient mice (Cbfa1(-/-)) the lack of mature osteoblasts is associated
      to incomplete bone mineralization. An important aim of modern biology is the
      development of new molecular tools for identification of therapeutic approaches.
      Recent discoveries in cell and molecular biology enabled researchers in the bone
      tissue-engineering field to develop new strategies for gene and cell-based
      therapies. This review summarizes the process of osteogenic differentiation from
      mesenchymal stem cells and the importance of bone regeneration is discussed. In
      particular, given the increasing interest in the study of the transcription
      factor Runx2, this review highlights the role of this target gene and addresses
      recent strategies using Runx2 for bone regeneration.

PMID- 22139790
TI  - Prevalence of diagnosed adult immune thrombocytopenia in the United Kingdom.
AB  - INTRODUCTION: Data regarding the prevalence of immune thrombocytopenia (ITP) is
      limited, and is derived from North American population-based analyses. Therefore,
      the authors conducted the first study outside the United States (US) using the
      United Kingdom (UK) General Practice Research Database (GPRD) to estimate the
      adult prevalence of ITP in the UK. METHODS: This study estimated the diagnosed
      prevalence of ITP in the adult population in UK using the GPRD from January 1,
      1992 to December 31, 2009. RESULTS: The unadjusted, overall 18-year period
      prevalence was 50.29/100,000 (95% CI: 48.51, 52.06). The age- and gender
      adjusted, overall 18-year period prevalence was 50.00/100,000 (95% CI: 49.20,
      50.90). ITP prevalence was lower in adults aged 18-49 years of age
      (30.09/100,000, 95% CI: 28.27, 31.90) than in older adults aged 50-64 years of
      age (58.22/100,000, 95% CI: 53.88, 62.57) or >=65 years of age (93.80/100,000,
      95% CI: 88.76, 98.85). Prevalence was higher among females (59.32/100,000, 95%
      CI: 56.63, 62.01) than in males (40.66/100,000, 95% CI: 38.36, 42.96). Prevalence
      in the GPRD increased over time (1992 [16.33/100,000, 95% CI: 13.70, 19.00], 2000
      [36.93/100,000, 95% CI: 34.50, 39.30], and 2009 [58.49/100,000, 95% CI: 55.80,
      61.20]). CONCLUSION: This new analysis of general practice in the UK provides
      robust prevalence estimates of diagnosed ITP among adults in Europe. ITP
      prevalence is higher in women and increases with age and over time.

PMID- 22139791
TI  - Contralesional hemisphere control of the proximal paretic upper limb following
      stroke.
AB  - Cathodal transcranial direct current stimulation (c-tDCS) can reduce excitability
      of neurons in primary motor cortex (M1) and may facilitate motor recovery after
      stroke. However, little is known about the neurophysiological effects of tDCS on
      proximal upper limb function. We hypothesized that suppression of contralesional
      M1 (cM1) excitability would produce neurophysiological effects that depended on
      the severity of upper limb impairment. Twelve patients with varying upper limb
      impairment after subcortical stroke were assessed on clinical scales of upper
      limb spasticity, impairment, and function. Magnetic resonance imaging was used to
      determine lesion size and fractional anisotropy (FA) within the posterior limbs
      of the internal capsules indicative of corticospinal tract integrity.
      Excitability within paretic M1 biceps brachii representation was determined from
      motor-evoked potentials during selective isometric tasks, after cM1 sham
      stimulation and after c-tDCS. These neurophysiological data indicate that c-tDCS
      improved selective proximal upper limb control for mildly impaired patients and
      worsened it for moderate to severely impaired patients. The direction of the
      neurophysiological after effects of c-tDCS was strongly related to upper limb
      spasticity, impairment, function, and FA asymmetry between the posterior limbs of
      the internal capsules. These results indicate systematic variation of cM1 for
      proximal upper limb control after stroke and that suppression of cM1 excitability
      is not a "one size fits all" approach.

PMID- 22139793
TI  - Charcoal-induced pseudomelanosis ilei.

PMID- 22139794
TI  - Three-dimensional contrast-enhanced endoscopic ultrasound for the     diagnosis
      of autoimmune pancreatitis.

PMID- 22139792
TI  - TRPV1-dependent and -independent alterations in the limbic cortex of neuropathic
      mice: impact on glial caspases and pain perception.
AB  - During neuropathic pain, caspases are activated in the limbic cortex. We
      investigated the role of TRPV1 channels and glial caspases in the mouse prelimbic
      and infralimbic (PL-IL) cortex after spared nerve injury (SNI). Reverse
      transcriptase-polymerase chain reaction, western blots, and immunfluorescence
      showed overexpression of several caspases in the PL-IL cortex 7 days postinjury.
      Caspase-3 release and upregulation of AMPA receptors in microglia, caspase-1 and
      IL-1beta release in astrocytes, and upregulation of Il-1 receptor-1, TRPV1, and
      VGluT1 in glutamatergic neurons, were also observed. Of these alterations, only
      those in astrocytes persisted in SNI Trpv1(-/-) mice. A pan-caspase inhibitor,
      injected into the PL-IL cortex, reduced mechanical allodynia, this effect being
      reduced but not abolished in Trpv1(-/-) mice. Single-unit extracellular
      recordings in vivo following electrical stimulation of basolateral amygdala or
      application of pressure on the hind paw, showed increased excitatory pyramidal
      neuron activity in the SNI PL-IL cortex, which also contained higher levels of
      the endocannabinoid 2-arachidonoylglycerol. Intra-PL-IL cortex injection of
      mGluR5 and NMDA receptor antagonists and AMPA exacerbated, whereas TRPV1 and AMPA
      receptor antagonists and a CB(1) agonist inhibited, allodynia. We suggest that
      SNI triggers both TRPV1-dependent and independent glutamate- and caspase-mediated
      cross-talk among IL-PL cortex neurons and glia, which either participates or
      counteracts pain.

PMID- 22139795
TI  - Estimation of treatment effect for the sequential parallel design.
AB  - The sequential parallel clinical trial is a novel clinical trial design being
      used in psychiatric diseases that are known to have potentially high placebo
      response rates. The design consists of an initial parallel trial of placebo
      versus drug augmented by a second parallel trial of placebo versus drug in the
      placebo non-responders from the initial trial. Statistical research on the design
      has focused on hypothesis tests. However, an equally important output from any
      clinical trial is the estimate of treatment effect and variability around that
      estimate. In the sequential parallel trial, the most important treatment effect
      is the effect in the overall population. This effect can be estimated by
      considering only the first phase of the trial, but this ignores useful
      information from the second phase of the trial. We develop estimates of treatment
      effect that incorporate data from both phases of the trial. Our simulations and a
      real data example suggest that there can be substantial gains in precision by
      incorporating data from both phases. The potential gains appear to be greatest in
      moderate-sized trials, which would typically be the case in phase II trials.

PMID- 22139796
TI  - Robotic thyroid surgery: Clinical and anatomic considerations.
AB  - Robotic thyroid surgery is a relatively new technique that provides the patient
      with the aesthetic advantage of a surgery without a scar in the anterior cervical
      region. The use of this technique, however, forces the surgeon to view the
      anatomy from a different vantage point, concomitantly providing the surgeon with
      a challenge with respect to dissection and sound oncologic ablation. It is
      important to note that robotic surgery used in this fashion is not limited access
      but rather requires a greater surface area of dissection to reach the surgical
      target. This article will discuss the relevant anatomy, operative goals, robotic
      technique, and clinical considerations of robotic thyroid surgery.

PMID- 22139797
TI  - Vaspin in obesity and diabetes: pathophysiological and clinical significance.
AB  - Vaspin (visceral adipose tissue-derived serpin; serpinA12) was originally
      identified as an adipokine, which is predominantly secreted from visceral adipose
      tissue in Otsuka Long-Evans Tokushima fatty (OLETF), an animal model of obesity
      and type 2 diabetes. Consistent with that higher vaspin serum concentrations and
      increased vaspin mRNA expression in human adipose tissue were found to be
      associated with obesity, insulin resistance, and type 2 diabetes in humans.
      However, the mechanisms how vaspin secretion may be linked to deterioration of
      glucose metabolism and insulin sensitivity are not entirely understood. Vaspin
      serum concentrations show a food intake-related diurnal variation. Vaspin is also
      expressed in the skin, hypothalamus, pancreatic islets, and stomach.
      Administration of vaspin to obese mice improves glucose tolerance, insulin
      sensitivity, and reduces food intake. Until now molecular target(s) of vaspin and
      its mode of action are unknown. Thus, identification of the proteases, which are
      inhibited by vaspin may lead to the development of novel strategies in the
      treatment of obesity, diabetes and insulin resistance. This review discusses the
      clinical relevance of vaspin in the pathophysiology of obesity and type 2
      diabetes.

PMID- 22139799
TI  - Age: "a natural anesthetic" in pain perception during the transrectal ultrasound
      guided prostate biopsy procedure.
AB  - INTRODUCTION: The purpose of this study was to evaluate how the age factor might
      influence the tolerance biopsy examination, and then choose the modality of a
      local or general anesthetic technique. MATERIALS AND METHODS: This study
      evaluated 248 consecutive patients undergoing transrectal ultrasound-guided
      prostate biopsy for the first time. Each patient was treated under local
      anesthesia with lidocaine spray (10gr/100ml). Patients were divided into two
      groups according to age: Group A) 112 with age range <=65 years, Group B) 136
      with age range >65 years. Our first aim was to obtain a schedule of 14 biopsy
      samples in both groups. After the procedure each patient was given a verbal
      numeric pain scale (VNS), which was designed with 0 representing absence of pain
      and 10 the maximum pain they perceived in life. RESULTS: The average pain
      assessed with VNS was around 4.2 (2-8) and 2.8 (0-6) for the patients in Group A
      and Group B, respectively. The two groups appeared to be homogeneous in terms of
      pain perception regarding PSA value and gland volume, and appeared to have
      different pain scores with regard to age. In fact, the first group of patients,
      with the same anesthetic technique used, perceived more intense pain sensations
      related to acute biopsy. CONCLUSIONS: In conclusion, we can say that a local
      anesthetic in clinical practice in the course of prostate biopsy is more
      sensitive if performed in a person aged 65 years.

PMID- 22139798
TI  - Inhibition of the NADPH oxidase regulates heme oxygenase 1 expression in chronic
      myeloid leukemia.
AB  - BACKGROUND: Patients with chronic myelogenous leukemia (CML) in blast crisis have
      a poor response to tyrosine kinase inhibitors designed to inhibit the breakpoint
      cluster region-v-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1)
      oncogene. Recent work has demonstrated that heme oxygenase 1 (HO-1) expression is
      increased in BCR-ABL1-expressing cells and that the inhibition of HO-1 in CML
      leads to reduced cellular growth, suggesting that HO-1 may be a plausible target
      for therapy. The objective of the current study was to clarify the mechanism of
      HO-1 overexpression and the role of the nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase as a contributor to this mechanism in CML. METHODS: HO
      1 expression was evaluated in bone marrow specimens from patients with CML in
      various stages of disease, in a transplantation-based model for CML, and in CML
      cell lines. Chemical and genetic inhibition of the NADPH oxidase was carried out
      in CML cells. RESULTS: Specimens from patients with CML in blast crisis displayed
      higher levels of HO-1 staining than specimens from patients with CML in chronic
      or accelerated phase. HO-1 up-regulation in BCR-ABL1-expressing cells was
      suppressed by diphenyleneiodonium (DPI), a chemical inhibitor of the NADPH
      oxidase. Targeting the NADPH oxidase through RNA interference (RNAi) to Ras
      related C3 botulinum toxin substrate 1 (Rac1), a dominant-negative Rac1 construct
      or an inhibitor of Rac1 activity also blunted HO-1 protein expression. Moreover,
      inhibition of the NADPH oxidase by RNAi directed toward the 47-kd cytosolic
      subunit of Nox (p47phox) similarly abrogated HO-1 levels. CONCLUSIONS: BCR-ABL1
      expression up-regulated HO-1, a survival factor for CML cells. This up-regulation
      was more pronounced in blast crisis CML relative to early stage disease and was
      mediated by the NADPH oxidase components Rac1 and p47phox. The expression of
      p47phox was increased in BCR-ABL1-expressing cells.

PMID- 22139800
TI  - Pancreatic metastasis from renal cell carcinoma.
AB  - BACKGROUND: Pancreatic metastases from renal cell carcinoma are uncommon.
      METHODS: Retrospective study of 8 patients with a diagnosis of pancreatic
      metastasis from renal cell carcinoma observed in our Institute. RESULTS: Patients
      were 6 (75%) males and 2 (25%) females. Mean age was 65.3 years. In 5 patients
      (57.1%), symptoms were present. The median interval of onset from nephrectomy was
      10 years. No cases of synchronous pancreatic metastases were observed. Surgical
      resection was performed in 7 (87.5%) patients. At pathological examination,
      solitary metastases were identified in 5 patients (71.4%). No post-operative
      mortality was observed; the morbidity rate was 42.8%. In the group of patients
      who underwent pancreatic resection, median overall survival was 43.0 months
      (range 12.9-74.5), median disease-free survival was 23.6 months (range 9.9-74.5).
      CONCLUSIONS: Pancreatic metastasis from renal cell carcinoma typically occurs
      after a long period from the initial nephrectomy, and seems to be related to a
      good prognosis.

PMID- 22139801
TI  - [Sacral hitch vesical pexy: a new ancillary technique for ureteroneocystostomy].
AB  - BACKGROUND: To describe the Sacral Hitch, vesical pexys to sacral promontory, an
      alternative technique to the Psoas Hitch when this is impossible to perform. We
      report intraoperative complications, and long-term functional results. METHODS:
      From 1989 to date we performed 66 ureteroneocystostomies (UNCS) (transbladder
      technique and Politano-Leadbetter antireflux plasty): 51 with ancillary "Psoas
      Hitch" (11 Casati-Boari); 15 with "Sacral Hitch" because of the intraoperative
      finding of deficiency or lack of psoas tendon. Note of technique. Ureter and
      bladder are dissected as usual. Sacral Hitch: left lateralization of sigmoid and
      exposition of sacral promontory; longitudinal incision and divarication of
      peritoneum; smooth dissection of fat tissue, displacement of medium sacral
      vessels and visualization of neurovascular bundles. Direct fixation of the
      dome/posterior aspect of bladder to anterior longitudinal ligament above
      promontory. RESULTS: Among the patients who underwent the Psoas Hitch technique,
      3 (5.4%) showed hypoesthesia, acute pain and impossible flexion of the thigh on
      hip with EMG positive for femoral (1) and genito-femoral (2) neuropathy. The re
      operation in 2 cases solved the symptoms. One case resolved conservatively with
      corticoids, tricyclic antidepressants (Amitriptyline) and antiepileptics
      (gabapentin). Mean follow-up was 115 months (8-252); two stenosis of anastomosis.
      Sacral Hitch: (15 pts), mean follow-up: 47 months (range 4-110), no stenosis of
      anastomosis 0%; transfusion rate 0%. DISCUSSION: The psoas tendon deficiency or
      its congenital absence (children or women) requires the direct fixation to the
      muscle, an inadequate and weak target and housing of important sensitive-motor
      nerves (Genito-femoral, femoral and latero-cutaneous). A "Psoas-Syndrome" could
      be present in 5.1% and a re-operation could be necessary. The sacral promontory
      represents an affixation target already successfully adopted in other surgery
      specialties (Gynaecology, Orthopaedic and General Surgery) and gives to UNCS a
      stiffness plate and an effective bladder cranialization. CONCLUSIONS. Sacral
      Hitch Vesical Pexys represents an ancillary procedure to UNCS and surgeons should
      keep it in mind in cases of difficult finding of the psoas muscle tendon.

PMID- 22139802
TI  - [Ductal carcinoma of the prostate: impact on survival and therapeutic
      controversies of a rare tumor].
AB  - Prostate cancer is a disease with a variable clinical course. The possible impact
      on oncological outcome of non-acinar prostate cancer has not been established
      yet, especially for ductal adenocarcinoma due to its low frequency, so that its
      clinical management is not well codified. The disease occurs more often already
      at an advanced stage of diagnosis, with clinically detectable tumors and advanced
      pathological stage, partly because of the lack of specific tumor markers, given
      the poor correlation between PDA and PSA values. In the period between 1997 and
      2010 56 patients with PDA on a total of 1265 new diagnoses of cancer were
      identified, for an overall incidence of 4.5%. 41 patients (75%) had a PDA type II
      histology, while 15 patients (25%) a PDA type I (pure form).  Generally, a
      surgical treatment was carried out in patients with life expectancy greater than
      10/15 years/under 70 years of age, non-metastatic tumors and found to be liable
      to local resection; radiation therapy was given with 70 Gy in cases with a
      shorter life expectancy and/or an illness judged unresectable for local
      extension; hormonal therapy was indicated in all other clinical situations. For
      all patients, the clinical and pathologic data and follow-ups were re-evaluated.
      The overall survival and disease-free survival were then analyzed. Given the low
      incidence of this pathology the relevant literature is poor and therefore the
      therapeutic approach is not univocal. This paper retrospectively reviews our
      experience with prostatic ductal adenocarcinoma.

PMID- 22139803
TI  - Analysis of costs of transrectal prostate biopsy.
AB  - INTRODUCTION: Literature reports mortality and morbidity data from prostatic
      carcinoma which permit a better use of some routine diagnostic tools such as
      transrectal ultrasound-guided biopsy. The aim of this work is to quantify the
      overall cost of transrectal ultrasound biopsy of the prostate (TRUSB) and to
      assess the economic impact of current procedures for diagnosing prostatic
      carcinoma. MATERIALS AND METHODS: The total cost of TRUSB was calculated with
      reference to 247 procedures performed in 2008. The following cost factors were
      evaluated: personnel, materials, maintenance/depreciation of the equipment,
      energy consumption, and hospital overheads. A literature review was also carried
      out to check if our extrapolated costs corresponded to those of other authors
      worldwide, and to consider them in the wider framework of the economic
      effectiveness of strategies for early diagnosis of cancer of the prostate.
      RESULTS: The overall cost of TRUSB (8 samples) was EUR 249,000, obtained by
      adding together the costs of: personnel (EUR 160,000); materials (EUR 59,000);
      equipment maintenance and depreciation (EUR 12,400); energy consumption (EUR0,1);
      hospital overheads (EUR 17,500). With extended or saturation biopsies the cost
      increases for the more time needed by pathologists and can be calculated as EUR
      300,000. The literature review points out TRUSB as an invasive tool for
      diagnosing prostatic carcinoma, clinically and economically controversial. Post
      mortem data report the presence of cancer cells in the prostate of 50% of 70-year
      old men, while extrapolations calculate a morbidity rate from prostatic carcinoma
      in 9.5% of 50-year-old men. It is therefore obvious that randomized prostatic
      biopsies, methods apart, have a good probability of being positive. This
      probability varies with the patient's age, the level of prostate specific antigen
      (PSA), the density of PSA/cm3 of prostate volume (PSAD), and the detection by
      digital exploration and/or positive transrectal ultrasound. CONCLUSIONS. Despite
      the severe application of all these criteria and the critical assessment of the
      patient's general conditions, TRUSB is indicated for 16% of the male population
      over 50 years of age, with obvious economic consequences. Quite recently the
      clinical utility of assays of PSA derivatives (such as Pro-2PSA) has gained more
      and more importance. The Pro-2PSA seems to reduce the use of TRUSB.

PMID- 22139804
TI  - [Neo-urethroclitoroplasty according to Petrovic].
AB  - INTRODUCTION: We present a refinement to our original technique in MtF gender
      reassignment surgery. Our goal was to construct a neoclitoris, which is wet and
      covered with urethral neoprepuce. Since 1995 more than 300 transgender MtF
      patients have been operated at our institution. Our refinement has been applied
      to 12 cases and showed both excellent functional and cosmetic results during
      midterm follow-up. PATIENTS AND METHODS: During 2010 several sex reassignment
      surgeries have been performed using our new technique that includes: bilateral
      orchiectomy, removal of corpora cavernosa of the penis, formation of the
      neourethra with neomeatus, neovaginoplasty by inversion of penoscrotal skin
      flaps, construction of the neoclitoris with preservation of the neurovascular
      bundle and exterior vulva formation. The refinement consists in creating a
      neoclitoris embedded in urethral mucosa using urethral flaps. These flaps are in
      continuity with the previously spatulated urethra. The urethral plate is further
      incised distally in a Y fashion. The urethral flaps are sutured around the
      neoclitoris to form a neo-urethroclitoris covered by urethral neoprepuce, which
      resembles a real female clitoris. The neoclitoris is positioned in the anatomical
      position of the male suspensory ligament of the penis that is also the natural
      anatomical position of the female clitoris. RESULTS: With this method we are able
      to construct a clitoris with a normal sensitivity embedded in urethral mucosa
      that remains wet and hairless. It can be easily stimulated during sexual
      intercourse, as most of the patients reported great satisfaction and ability to
      reach orgasm. DISCUSSION: We want to emphasize how both the cosmetic results and
      functionality of the neovagina and neoclitoris are important in this type of
      surgery for the quality of life of our patients. We are still far from a perfect
      surgical solution, but we are further improving our technique and follow our aims
      step by step.

PMID- 22139805
TI  - [Foreign bodies in urinary bladder: a clinical case].
AB  - OBJECTIVES: A pencil in the urinary bladder is an unusual problem for urologists.
      We present a case in a 44-year-old female with an eyeliner pencil self-introduced
      into the urethra. MATERIALS AND METHODS: The patient was referred to us with a
      recent history of "ingestion of foreign body". The clinical presentation,
      radiologic data, and treatment were reported. RESULTS: The patient had a pencil
      placed sideways in the urinary bladder, with focal perforation of the left wall.
      A cystoscopy was performed and the pencil was removed at the same time by using
      grasping forceps and hydraulic overdistention of the urinary bladder.
      CONCLUSIONS: Bladder is the most common location of foreign bodies of the
      urogenital tract, almost always due to self-insertion into the urethra for the
      purpose of masturbation or as a result of non-inhibited or altered behavior due
      to psychiatric diseases, or to the influence of drugs. Most patients were too
      ashamed to admit they had inserted or applied any object and usually presented
      when a complication had occurred such as difficulty in voiding, hematuria, pain
      or swelling, extravasations or abscess formation. The treatment can be
      endoscopic, and it depends on the type of the foreign object and the operator's
      skills.

PMID- 22139806
TI  - Hematuria one-stop clinic: first experience in Italy with 150 cases.
AB  - OBJECTIVES: Starting from the UK experience, we decided to test both the
      feasibility and the advantages of this diagnostic pathway now established in an
      Italian hospital. We analyzed the outcomes in detecting transitional cell
      carcinoma (TCC) of the bladder, other malignant and non-malignant conditions.
      MATERIALS AND METHODS: Between April and December 2010, one hundred and fifty
      patients presenting with hematuria were referred to the Hematuria One Stop Clinic
      (HOSC) at our Institution. Each patient underwent a visit, a Urinary Tract
      Ultrasound, a Cystoscopy and CT IVP in selected cases (evidence of alterations or
      lesions of the renal parenchyma, presence of stones of the urinary tract,
      evidence of doubtful or positive urinary cytology). Where a TCC of the bladder
      was diagnosed, the patient underwent TUR-BT. In other cases (stones, BPH etc.)
      the appropriate therapeutic pathway was followed. RESULTS: 25.3% of patients with
      hematuria were found to have a bladder cancer; 21.3% had a urinary stone (2% in
      the bladder); 1.3% had prostate cancer; 1.3% had a renal cell carcinoma. The mean
      age was 69.8 yrs. 6% of the patients (23.6% on patients with TCC of the bladder)
      had a G3 disease. The mean time from admission to the HOSC until the operation
      day, in case of TCC of the bladder, was 10.61 days. CONCLUSIONS: The Italian
      experience of the One Stop Clinic confirms a high rate of bladder cancer
      detection. Furthermore, a high rate of non-malignant conditions was detected,
      stressing the importance of the HOSC not only as a cancer clinic but as a
      complete general urological clinic. We report a shorter waiting time to
      operation, especially for bladder TCC G3 patients.

PMID- 22139807
TI  - [Use of zoledronic acid in patients with prostate cancer bone metastases: control
      of pain and musculoskeletal complications].
AB  - Background. Patients suffering from prostatic carcinoma are at high risk of
      having bone complications because of the metastatic progression of the disease to
      the skeleton and the consequences of androgenic deprivation. Zoledronic acid is a
      potent inhibitor of the bone resorption mediated by the osteoclasts, and is the
      only bisphosphonate whose capacity of reducing significantly the skeleton
      morbidity in patients with bone metastases is statistically proved. Methods. To
      attest tolerability and efficacy of zoledronic acid in preventing unfavorable
      skeletal events and in reducing osteomuscular pain, 25 patients - aged 75 years,
      suffering from hormone-responsive prostatic carcinoma under hormonal therapy with
      bone metastases, have been followed and subjected to IV monthly infusion of 4 mg
      zoledronic acid for 12 consecutive months, associated to daily intake of calcium
      and multivitamin supplementations. Results. At the end of the study, a sensible
      improvement in their clinical conditions and in their perception of the pain has
      been recorded in 23 patients and valued through a set of questions (Brief Pain
      Inventory). Conclusions. Zoledronic acid is therefore confirmed to be an
      effective medicine in preventing the skeleton complications and in controlling
      the painful symptoms in patients suffering from prostatic carcinoma with bone
      metastases.

PMID- 22139808
TI  - System and SAR characterization in parallel RF transmission.
AB  - The markedly increased degrees of freedom introduced by parallel radiofrequency
      transmission presents both opportunities and challenges for specific absorption
      rate (SAR) management. On one hand they enable E-field tailoring and SAR
      reduction while facilitating excitation profile control. On other hand they
      increase the complexity of SAR behavior and the risk of inadvertently
      exacerbating SAR by improper design or playout of radiofrequency pulses. The
      substantial subject-dependency of SAR in high field magnetic resonance can be a
      compounding factor. Building upon a linear system concept and a calibration
      scheme involving a finite number of in situ measurements, this work establishes a
      clinically applicable method for characterizing global SAR behavior as well as
      channel-by-channel power transmission. The method offers a unique capability of
      predicting, for any excitation, the SAR and power consequences that are specific
      to the subject to be scanned and the MRI hardware. The method was validated in
      simulation and experimental studies, showing promise as the foundation to a
      prospective paradigm where power and SAR are not only monitored but, through
      prediction-guided optimization, proactively managed.

PMID- 22139809
TI  - Body mass index correlates negatively with white matter integrity in the fornix
      and corpus callosum: a diffusion tensor imaging study.
AB  - Overweight or obese body habitus is associated with cognitive deficits, impaired
      brain function, gray matter atrophy, and white matter (WM) hyperintensities.
      However, few diffusion tensor imaging (DTI) studies have assessed WM integrity in
      relation to overweight or obese status. This study assessed relationships between
      body mass index (BMI) and values of DTI parameters among 51 normal weight (lean),
      overweight, and obese participants who were otherwise healthy. BMI correlated
      negatively with fractional anisotropy and axial eigenvalues (lambda(1)) in the
      body of corpus callosum (CC), positively with mean diffusivity and radial
      eigenvalues (See figure in text) in the fornix and splenium of CC, and positively
      with lambda(1) in the right corona radiata (CR) and superior longitudinal
      fasciculus (SLF). These data indicate that BMI correlates negatively with WM
      integrity in the fornix and CC. Furthermore, the different patterns of BMI
      related differences in DTI parameters at the fornix, body, and splenium of the
      CC, and the right CR and SLF suggest that different biological processes may
      underlie BMI-related impairments of WM integrity in different brain regions.

PMID- 22139810
TI  - "One-step" preparation of thiol-ene clickable PEG-based thermoresponsive
      hyperbranched copolymer for in situ crosslinking hybrid hydrogel.
AB  - A well-defined poly(ethylene glycol) based hyperbranched thermoresponsive
      copolymer with high content of acrylate vinyl groups was synthesized via a "one
      pot and one-step" deactivation enhanced atom transfer radical polymerization
      approach, which provided an injectable and in situ crosslinkable system via
      Michael-type thiol-ene reaction with a thiol-modified hyaluronan biopolymer. The
      hyperbranched structure, molecular weight, and percentage of vinyl content of the
      copolymer were characterized by gel permeation chromatography and (1)H NMR. The
      lower critical solution temperature of this copolymer is close to body
      temperature, which can result in a rapid thermal gelation at 37  degrees C. The
      scanning electron microscopy analysis of crosslinked hydrogel showed the network
      formation with porous structure, and 3D cell culture study demonstrated the good
      cell viability after the cells were embedded inside the hydrogel. This injectable
      and in situ crosslinking hybrid hydrogel system offers great promise as a new
      class of hybrid biomaterials for tissue engineering. 

PMID- 22139813
TI  - EUS 2010 in Shanghai - Highlights and Scientific Abstracts.

PMID- 22139814
TI  - Diagnosing imputation models by applying target analyses to posterior replicates
      of completed data.
AB  - Multiple imputation fills in missing data with posterior predictive draws from
      imputation models. To assess the adequacy of imputation models, we can compare
      completed data with their replicates simulated under the imputation model. We
      apply analyses of substantive interest to both datasets and use posterior
      predictive checks of the differences of these estimates to quantify the evidence
      of model inadequacy. We can further integrate out the imputed missing data and
      their replicates over the completed-data analyses to reduce variance in the
      comparison. In many cases, the checking procedure can be easily implemented using
      standard imputation software by treating re-imputations under the model as
      posterior predictive replicates. Thus, it can be applied for non-Bayesian
      imputation methods. We also sketch several strategies for applying the method in
      the context of practical imputation analyses. We illustrate the method using two
      real data applications and study its property using a simulation.

PMID- 22139816
TI  - Temporal and geographic variations of Waldenstrom macroglobulinemia incidence: a
      large population-based study.
AB  - BACKGROUND: Waldenstrom macroglobulinemia (WM) is a non-Hodgkin lymphoma (NHL)
      subtype. Little is known about the incidence and trends for this disease in the
      United States. METHODS: Twenty-year data from the Surveillance, Epidemiology, and
      End Results (SEER) program were used for this study. SEER*Stat was used for data
      analysis. RESULTS: Of the 95,797 cases of NHL diagnosed between 1988 and 2007 in
      9 SEER registries, 1835 (1.9%) were new cases of WM. Median age at diagnosis of
      WM was 73 years. The overall annual age-adjusted incidence was 0.38 per 100,000
      persons per year, which increased with age, ranging from 0.03 in patients aged
      <50 years to 2.85 in patients aged >=80 years. The incidence of WM was higher in
      men (0.54) than in women (0.27; P < .001) and was higher in whites (0.41) than in
      African Americans (0.18) or other races (0.21; P < .05). The annual percentage
      change for the whole population was 1.01% (P > .05). The annual percentage change
      was 1.21% for whites (P < .05) and 0.80% (P > .05) for nonwhites. Significant
      annual percentage change increases were seen in the group aged 70 to 79 years
      (1.24%; P < .05) and in 3 geographic registries (P < .001). CONCLUSIONS: Although
      the overall incidence of WM remained steady over time, significant increases in
      incidence were seen over the past 20 years in whites, in those aged 70 to 79
      years, and in 3 geographic registry areas.

PMID- 22139815
TI  - The neocortical network representing associative memory reorganizes with time in
      a process engaging the anterior temporal lobe.
AB  - During encoding, the distributed neocortical representations of memory components
      are presumed to be associatively linked by the hippocampus. With time, a
      reorganization of brain areas supporting memory takes place, which can ultimately
      result in memories becoming independent of the hippocampus. While it is theorized
      that with time, the neocortical representations become linked by higher order
      neocortical association areas, this remains to be experimentally supported. In
      this study, 24 human participants encoded sets of face-location associations,
      which they retrieved 1 or 25 h later ("recent" and "remote" conditions,
      respectively), while their brain activity was recorded using whole-head
      magnetoencephalography. We investigated changes in the functional interactions
      between the neocortical representational areas emerging over time. To assess
      functional interactions, trial-by-trial high gamma (60-140 Hz) power correlations
      were calculated between the neocortical representational areas relevant to the
      encoded information, namely the fusiform face area (FFA) and posterior parietal
      cortex (PPC). With time, both the FFA and the PPC increased their functional
      interactions with the anterior temporal lobe (ATL). Given that the ATL is
      involved in semantic representation of paired associates, our results suggest
      that, already within 25 h after acquiring new memory associations, neocortical
      functional links are established via higher order semantic association areas.

PMID- 22139817
TI  - Inhibition of activator protein 1 signaling abrogates transforming growth factor
      beta-mediated activation of fibroblasts and prevents experimental fibrosis.
AB  - OBJECTIVE: To investigate whether c-Jun and c-Fos contribute to the pathologic
      activation of fibroblasts in systemic sclerosis (SSc) and to evaluate the
      antifibrotic potential of selective activator protein 1 (AP-1) inhibition.
      METHODS: Expression of c-Jun and c-Fos was determined by real-time polymerase
      chain reaction (PCR) and immunohistochemical analysis. Fibroblasts were
      stimulated with transforming growth factor beta (TGFbeta) and incubated with T
      5224, a small-molecule inhibitor of AP-1, or were transfected with small
      interfering RNA (siRNA) duplexes against c-Jun and c-Fos. Collagen synthesis was
      quantified by real-time PCR and hydroxyproline assay. Differentiation of resting
      fibroblasts into myofibroblasts was assessed by staining for alpha-smooth muscle
      actin and stress fibers. The antifibrotic potential of T-5224 was evaluated in
      mouse models of dermal fibrosis induced by bleomycin or by adenoviral
      overexpression of a constitutively active TGFbeta receptor type I. RESULTS: Up
      regulation of c-Jun and c-Fos was detected in mouse models of SSc and in the skin
      and dermal fibroblasts of patients with SSc. Stimulation of healthy fibroblasts
      with TGFbeta induced the expression of c-Jun and c-Fos. Treatment with T-5224 or
      nucleofection with siRNA directed against c-Jun and c-Fos abrogated the
      profibrotic effects of TGFbeta. T-5224 decreased the release of collagen
      selectively in SSc fibroblasts. T-5224 was well tolerated and prevented dermal
      fibrosis induced by bleomycin or by adenoviral activation of TGFbeta signaling.
      CONCLUSION: AP-1 is up-regulated in a TGFbeta-dependent manner in SSc. The
      selective AP-1 inhibitor T-5224 reduced collagen synthesis selectively in SSc
      fibroblasts and efficiently prevented the development of experimental dermal
      fibrosis. Thus, AP-1 might be a promising new molecular target for the treatment
      of SSc.

PMID- 22139818
TI  - Stereoselective degradation of tebuconazole in rat liver microsomes.
AB  - The aim of this study was to assess the stereoselectivity of two tebuconazole
      [(RS)-1-p-chlorophenyl-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol]
      enantiomers in in vitro system (rat liver microsomes). The analytes were
      extracted with acetic ether and concentrations were determined by high
      performance liquid chromatography (HPLC) with a cellulose tris(3,5
      dimethylphenylcarbamate)-based chiral stationary phase. The degradation of rac
      tebuconazole (15 MUM) followed first-order kinetics, and the degradation of the S
      tebuconazole (t(1/2) = 22.31 min) was faster than that of the R-tebuconazole
      (t(1/2) = 48.76 min), but no significant difference between the enantiomers was
      found in the respective incubation (7.5 MUM for each). Kinetic assays showed that
      the K(m) was different between the two enantiomers (K(mR) = 14.83 +/- 2.19, K(mS)
      = 12.23 +/- 2.72). The interaction results revealed that there was competitive
      inhibition between S- and R-form, and there was a significant difference between
      the IC(50) of R- to S-tebuconazole and S- to R-tebuconazole (IC(50R/S)/IC(50S/R)
      = 4.98).

PMID- 22139819
TI  - Simultaneous variable flip angle-actual flip angle imaging method for improved
      accuracy and precision of three-dimensional T1 and B1 measurements.
AB  - A new time-efficient and accurate technique for simultaneous mapping of T(1) and
      B(1) is proposed based on a combination of the actual flip angle (FA) imaging and
      variable FA methods. Variable FA-actual FA imaging utilizes a single actual FA
      imaging and one or more spoiled gradient-echo acquisitions with a simultaneous
      nonlinear fitting procedure to yield accurate T(1)/B(1) maps. The advantage of
      variable FA-actual FA imaging is high accuracy at either short T(1) times or long
      repetition times in the actual FA imaging sequence. Simulations show this method
      is accurate to 0.03% in FA and 0.07% in T(1) for ratios of repetition time to T1
      time over the range of 0.01-0.45. We show for the case of brain imaging that it
      is sufficient to use only one small FA spoiled gradient-echo acquisition, which
      results in reduced spoiling requirements and a significant scan time reduction
      compared to the original variable FA method. In vivo validation yielded high
      quality 3D T(1) maps and T(1) measurements within 10% of previously published
      values and within a clinically acceptable scan time. The variable FA-actual FA
      imaging method will increase the accuracy and clinical feasibility of many
      quantitative MRI methods requiring T(1)/B(1) mapping such as dynamic contrast
      enhanced perfusion and quantitative magnetization transfer imaging.

PMID- 22139821
TI  - White matter structures associated with emotional intelligence: evidence from
      diffusion tensor imaging.
AB  - Previous studies of brain lesions, functional activity, and gray matter
      structures have suggested that emotional intelligence (EI) is associated with
      regions involved in the network of social cognition (SCN) and in somatic marker
      circuitry (SMC). Our new study is the first to investigate the association
      between white matter (WM) integrity and EI. We examined this relationship in the
      brain of healthy young adult men [n = 74, mean age = 21.5 years, standard
      deviation (SD) = 1.6] and women (n = 44, mean age = 21.9 years, SD = 1.4). We
      performed a voxel-based analysis of fractional anisotropy, which is an indicator
      of WM integrity, using diffusion tensor imaging and used a questionnaire (EI
      Scale) for measuring EI to identify the correlation of WM integrity with
      individual EI factor (intrapersonal, interpersonal, and situation management
      factors). Our results showed that (a) the intrapersonal factor of EI was
      positively correlated with WM integrity in the right anterior insula, and (b) the
      interpersonal factor of EI was associated with WM integrity in a part of the
      right inferior longitudinal fasciculus (ILF). The right anterior insula is one of
      the important nodes of the SMC, whereas the ILF connects the visual cortex and
      areas related to SCN, and thus, is a part of the SCN. Our findings further
      support the notion that the brain regions involved in the SCN and in the SMC are
      associated with EI.

PMID- 22139820
TI  - C-peptide predicts the remission of type 2 diabetes after bariatric surgery.
AB  - BACKGROUND: C-peptide is a surrogate of the pancreatic beta cell mass. However,
      the clinical significance of C-peptide in a diabetic patient after bariatric
      surgery has not been studied clearly. METHODS: From February 2005 to January
      2009, a total of 205 (124 females and 81 males) consecutive morbidly obese
      patients with type 2 diabetes mellitus (T2DM) enrolled in a surgically supervised
      weight loss program with at least 1 year follow-up were examined. Among them, 147
      patients (71.7%) received gastric bypass procedures, while the other 58 patients
      (28.3%) received restrictive-type procedures. RESULTS: The mean C-peptide before
      the surgery was 5.3 +/- 3.5 ng/ml. One hundred nineteen patients (58.0%) had an
      elevated C-peptide (>4 ng/ml), while 2 patients (1.0%) had a low C-peptide (<1.0
      ng/ml). Multivariate analysis confirmed that waist circumference, triglycerides,
      and HbA1c were the independent predictors for the elevation of C-peptide. It was
      observed that the mean C-peptide levels decreased to 1.7 +/- 0.9 ng/ml 1 year
      after bariatric surgery with a mean reduction of 64.1%. One year after surgery,
      160 patients (78.0%) out of a total of 205 patients had a remission of their
      T2DM. Patients in the bypass group had a higher diabetes remission rate (91.2%;
      134 out of 147) in comparison to patients in the restrictive group (44.8%; 26 out
      of 58, p < 0.001). The diabetes remission rates for those with preoperative C
      peptide <3, 3-6, and > 6 ng/ml were 26 out of 47 (55.3%), 87 out of 108 (82.0%),
      and 47 out of 52 (90.3%), p < 0.001, respectively. CONCLUSIONS: Baseline C
      peptide is commonly elevated in morbidly obese patients with T2DM. There was a
      marked reduction in C-peptide after a significant weight reduction 1 year after
      surgery with a T2DM remission rate of 78.0%. Thus, bariatric surgery is
      recommended for obesity-related T2DM patients with elevated C-peptide.

PMID- 22139822
TI  - Optimal multistage designs for randomised clinical trials with continuous
      outcomes.
AB  - Multistage designs allow considerable reductions in the expected sample size of a
      trial. When stopping for futility or efficacy is allowed at each stage, the
      expected sample size under different possible true treatment effects (delta) is
      of interest. The delta-minimax design is the one for which the maximum expected
      sample size is minimised amongst all designs that meet the types I and II error
      constraints. Previous work has compared a two-stage delta-minimax design with
      other optimal two-stage designs. Applying the delta-minimax design to designs
      with more than two stages was not previously considered because of computational
      issues. In this paper, we identify the delta-minimax designs with more than two
      stages through use of a novel application of simulated annealing. We compare them
      with other optimal multistage designs and the triangular design. We show that, as
      for two-stage designs, the delta-minimax design has good expected sample size
      properties across a broad range of treatment effects but generally has a higher
      maximum sample size. To overcome this drawback, we use the concept of admissible
      designs to find trials which balance the maximum expected sample size and maximum
      sample size. We show that such designs have good expected sample size properties
      and a reasonable maximum sample size and, thus, are very appealing for use in
      clinical trials.

PMID- 22139823
TI  - Challenging presentations of cavernous sinus thrombophlebitis.
AB  - AIM: The purpose of this study was to describe two challenging cases of septic
      cavernous sinus thrombosis (CST), which presented with vastly different clinical
      signs and symptoms. METHODS: We present two cases of CST with markedly differing
      clinical presentations, medical comorbidities, and degree of impairment. Initial
      imaging of each patient failed to show thromboembolic disease. RESULTS: Both
      patients required multiple imaging procedures to arrive at the correct diagnosis.
      Each child did respond to treatment once the correct diagnosis was made.
      CONCLUSION: CST can have a highly variable clinical presentation, from a subtle
      sixth nerve palsy to complete ophthalmoplegia and loss of periorbital sensation
      and corneal reflex. Onset of symptoms may be acute and fulminant or indolent and
      delayed. The diagnosis is challenging, requiring clinical suspicion and
      confirmation by imaging. These cases illustrate the importance of retaining
      clinical suspicion when cranial nerve palsies persist and how valuable rescanning
      a patient can be.

PMID- 22139824
TI  - B1b lymphocyte-derived antibodies control Borrelia hermsii independent of
      Fcalpha/MU receptor and in the absence of host cell contact.
AB  - The critical role of IgM in controlling pathogen burden has been demonstrated in
      a variety of infection models. In the murine model of Borrelia hermsii infection,
      IgM is necessary and sufficient for the rapid clearance of bacteremia.
      Convalescent, but not naive, B1b cells generate a specific IgM response against
      B. hermsii, but the mechanism of IgM-mediated protection is unknown. Here, we
      show that neither Fcalpha/MUR, a high-affinity receptor for IgM, nor IgM
      dependent complement activation is required for controlling B. hermsii. Bacteria
      in diffusion chambers with a pore size impermeable to cells were killed when
      diffusion chambers were implanted into either convalescent or passively immunized
      mice. Furthermore, adoptively transferred convalescent B1b cells in Rag1(-/-)
      mice produced specific IgM that also cleared B. hermsii in diffusion chambers
      independent of complement. These results demonstrate that IgM-mediated clearance
      of B. hermsii does not require opsonophagocytosis and indicate that a mechanism
      for in vivo B1b cell-mediated protection is through the generation of
      bactericidal IgM.

PMID- 22139825
TI  - Phase 2 trial of "sandwich" L-asparaginase, vincristine, and prednisone
      chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type,
      extranodal natural killer/T-cell lymphoma.
AB  - BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, is a
      distinct entity of lymphoid tissue. ENKTL is sensitive to radiotherapy (RT), but
      the prognosis is poorer than for other types of early lymphoma. The treatment
      schedule is controversial. METHODS: A phase 2 study was conducted of "sandwich"
      protocols, with earlier RT after an initial 2 to 3 cycles of LVP (L-asparaginase,
      vincristine, and prednisone), followed by further "consolidation" cycles.
      Patients aged 18 years and older who had previously untreated ENKTL and localized
      lesions in the upper aerodigestive tract were enrolled. The primary endpoints
      were objective response rate and complete remission rate. The secondary endpoints
      were 2-year overall survival, 2-year progression-free survival, and toxicity.
      This study is registered with www.Chictr.org, number ChicTR-TNC-00000394, and is
      ongoing for long-term follow-up. RESULTS: Twenty-six patients completed total
      therapy, which resulted in 88.5% response that included 21 patients (80.8%) with
      complete response (CR) and 2 patients (7.7%) with partial response. Three (11.5%)
      of 26 patients progressed during therapy. With a median follow-up of 27 months
      (range, 4-35 months), the 2-year overall survival was 88.5%, and the 2-year
      progression-free survival was 80.6%. Patients with CR had better prognosis than
      patients without CR. Only 2 patients (7.7%) experienced grade 3 leukocytopenia.
      No grade 4 toxicity or treatment-related deaths were observed. CONCLUSIONS: The
      research showed that the "sandwich" protocol of LVP combined with RT was a safe
      and effective treatment for localized nasal natural killer/T-cell lymphoma, and
      the results warrant further investigation into this protocol.

PMID- 22139826
TI  - Molecular bottlebrushes with polypeptide backbone prepared via ring-opening
      polymerization of NCA and ATRP.
AB  - A new type of molecular bottlebrush with poly-L-lysine (PLL) as backbone was
      synthesized via ROP followed by ATRP. A Nepsilon-bromoisobutyryl functionalized
      Nalpha-CBZ-L-lysine was firstly synthesized and converted in polymerizable alpha
      amino acid N-carboxyanhydride (NCA), which was then polymerized using Ni(0)
      transition metal complex to give well-defined bromo-functionalized
      homopolypeptide (PBrLL), from which we prepared two types of polypeptide
      bottlebrushes with polystyrene and poly(oligoethylene glycol methacrylate) as
      side-chains. PBrLL macroinitiator was demonstrated to have high initiation
      efficiency for ATRP, which allowed good control over side-chain length. CD and
      FTIR characterization revealed that both PBrLL macroinitiator and PLL backbone of
      bottlebrushes adopted alpha-helical conformation in appropriate solvents.

PMID- 22139827
TI  - Study on the metabolic mechanism of chiral inversion of S-mandelic acid in vitro.
AB  - Mandelic acid (MA) is generally used as a biological indicator of occupational
      exposure to styrene, which is classified as a class of hazardous environmental
      pollutants. It was found to undergo one-directional chiral inversion (S-MA to R
      MA) in Wistar and Sprague-Dawley rats in vivo. This study was aimed to explore
      the metabolic mechanism of chiral inversion of S-MA in vitro. S-MA was converted
      to R-MA in rat hepatocytes, whereas MA enantiomers remained unchanged in acidic
      and neutral phosphate buffers, HepG2 cells, and intestinal flora. In addition,
      the synthesized S-MA-CoA thioester was rapidly racemized and hydrolyzed to R-MA
      by rat liver homogenate and S9, cytosolic and mitochondrial fractions. The data
      suggest that chiral inversion of S-MA may involve the hydrolysis of S-MA-CoA, and
      its metabolic mechanism could be the same as that of 2-arylpropionic acid (2-APA)
      drugs.

PMID- 22139828
TI  - Predictors of functional impairment and pain in erosive osteoarthritis of the
      interphalangeal joints: comparison with controlled inflammatory arthritis.
AB  - OBJECTIVE: To compare levels of pain and functional limitation in patients with
      erosive osteoarthritis (OA) of the interphalangeal finger joints with those in
      patients with nonerosive OA and patients with controlled inflammatory arthritis
      affecting the hands, and to explore predictors of functional impairment in
      erosive OA. METHODS: A cross-sectional study including 270 patients with OA of
      the hands who were referred to rheumatology clinics was performed. A group of
      patients with inflammatory arthritis (rheumatoid arthritis or psoriatic
      arthritis) with a low Disease Activity Score in 28 joints (<3.2; n = 79) was
      examined. Levels of functional impairment (measured by the Functional Index for
      Hand OA [FIHOA] and Australian/Canadian OA Hand Index [AUSCAN]) and pain were
      compared between the groups. Predictors of functional impairment in erosive OA
      were evaluated by generalized linear models. RESULTS: Of 270 patients with hand
      OA, 167 (61.9%) were classified as having erosive OA. Despite a higher percentage
      of patients taking analgesics (almost 60%), patients with erosive OA had worse
      functional outcome and pain scores than patients with controlled inflammatory
      arthritis or nonerosive OA. Pain scores remained significantly higher in patients
      with erosive OA after correction for potential confounders. FIHOA and AUSCAN
      function scores showed a trend toward more disability in patients with erosive
      OA. Female sex and the number of radiographic affected joints (consisting of
      joints in the erosive and remodeled radiographic phases) were the strongest
      predictors of functional impairment in erosive OA. Whether the carpometacarpal
      joints were affected did not influence functional status in patients with erosive
      OA. CONCLUSION: Our findings indicate that patients with erosive OA have more
      functional impairment and significantly more pain compared to patients with
      controlled inflammatory arthritis affecting the hands. This highlights the
      significant clinical burden of erosive OA and warrants the search for new
      treatment strategies.

PMID- 22139829
TI  - Contrast enhancement in TOF cerebral angiography at 7 T using saturation and MT
      pulses under SAR constraints: impact of VERSE and sparse pulses.
AB  - Cerebral three-dimensional time of flight (TOF) angiography significantly
      benefits from ultrahigh fields, mainly due to higher signal-to-noise ratio and to
      longer T(1) relaxation time of static brain tissues; however, specific absorption
      rate (SAR) significantly increases with B(0). Thus, additional radiofrequency
      pulses commonly used at lower field strengths to improve TOF contrast such as
      saturation of venous signal and improved background suppression by magnetization
      transfer typically cannot be used at higher fields. In this work, we aimed at
      reducing SAR for each radiofrequency pulse category in a TOF sequence. We use the
      variable-rate selective excitation principle for the slab selective TOF
      excitation as well as the venous saturation radiofrequency pulses. In addition,
      magnetization transfer pulses are implemented by sparsely applying the pulses
      only during acquisition of the central k-space lines to limit their SAR
      contribution. Image quality, angiographic contrast, and SAR reduction were
      investigated as a function of variable-rate selective excitation parameters and
      of the total number of magnetization transfer pulses applied. Based on these
      results, a TOF protocol was generated that increases the angiographic contrast by
      more than 50% and reduces subcutaneous fat signal while keeping the resulting SAR
      within regulatory limits.

PMID- 22139830
TI  - Incidence of and impact of medications on colectomy in newly diagnosed ulcerative
      colitis in the era of biologics.
AB  - BACKGROUND: The cumulative incidence of colectomy and the impact of 5
      aminosalicylates (5-ASA), azathioprine, and antitumor necrosis factor (TNF)
      treatment on the long-term need for surgery are unknown in ulcerative colitis
      (UC) in the era of biologics. METHODS: This was an observational study of a
      referral center cohort. The cumulative incidence of UC-related colectomy was
      estimated using the Kaplan-Meier method. Independent predictors of surgery were
      identified using Cox proportional hazards regression with propensity scores
      adjustment. The electronic charts of 151 incident cases of UC from Nancy
      University Hospital, France, diagnosed between 2000 and 2008, were reviewed
      through January 2010. RESULTS: The median follow-up time per patient was 58
      months. Twenty-one (14%) underwent surgery. The cumulative probabilities of
      colectomy were respectively 1.3% and 13.5% at 1 and 5 years from the time of
      diagnosis. The probability of receiving oral mesalamine at 5 years was 68.1%. The
      corresponding figures were 48.9% for azathioprine and 29.0% for infliximab. For
      corticosteroids, methotrexate, and cyclosporin these figures were 75%, 8.8%, and
      11.5%, respectively. Using multivariate Cox proportional hazards regression
      analysis after propensity score adjustment, previous use of cyclosporin was the
      only independent predictor for colectomy (hazard ratio = 4.41; 95% confidence
      interval 1.75-1.13). CONCLUSIONS: About one-tenth of patients still require
      colectomy for UC at 5 years in the era of biologics. Oral 5-ASA, azathioprine,
      and anti-TNF therapy are not associated with a reduced need for colectomy.

PMID- 22139831
TI  - Economic benefits of bariatric surgery.
AB  - With the high prevalence of obesity and associated comorbidities, the costs of
      health services produce a great economic impact. The objective of this work was
      to evaluate the economic benefits of bariatric surgery and to relate the costs to
      the impact on the health of the individual. A historic cohort study was
      conducted, with review of medical charts of 194 patients who fulfilled the
      inclusion criteria for the study. The costs for medications, professional care,
      and examinations in the pre- and postoperative periods were analyzed, taking into
      consideration the comorbidities DM2, SAH, and dyslipidemia. The study
      demonstrated a reduction in the medical costs in the course of the postoperative
      period, in relation to expenses for medications, professional care, and
      examinations in the preoperative period. Comparing the preoperative expenses with
      different times in the postoperative period, a statistically significant
      difference was seen at all time evaluated (p < 0.001). The resolution of
      comorbidities was higher than 95% at 36 months after surgery. No statistically
      significant difference was seen with respect to the prevalence of comorbidities
      between the sexes in the pre- and postoperative periods (p > 0.05). With regard
      to age, younger patients showed lower rates of comorbidities in the pre- and
      postoperative periods (p < 0.001). The costs of the surgery are high, but the
      expenditures for medications, professional care, and examinations decrease
      progressively after the operation, where this is more evident in patients with
      more associated comorbidities.

PMID- 22139832
TI  - Estimating the agreement and diagnostic accuracy of two diagnostic tests when one
      test is conducted on only a subsample of specimens.
AB  - We focus on the efficient usage of specimen repositories for the evaluation of
      new diagnostic tests and for comparing new tests with existing tests. Typically,
      all pre-existing diagnostic tests will already have been conducted on all
      specimens. However, we propose retesting only a judicious subsample of the
      specimens by the new diagnostic test. Subsampling minimizes study costs and
      specimen consumption, yet estimates of agreement or diagnostic accuracy
      potentially retain adequate statistical efficiency. We introduce methods to
      estimate agreement statistics and conduct symmetry tests when the second test is
      conducted on only a subsample and no gold standard exists. The methods treat the
      subsample as a stratified two-phase sample and use inverse-probability weighting.
      Strata can be any information available on all specimens and can be used to
      oversample the most informative specimens. The verification bias framework
      applies if the test conducted on only the subsample is a gold standard. We also
      present inverse-probability-weighting-based estimators of diagnostic accuracy
      that take advantage of stratification. We present three examples demonstrating
      that adequate statistical efficiency can be achieved under subsampling while
      greatly reducing the number of specimens requiring retesting. Naively using
      standard estimators that ignore subsampling can lead to drastically misleading
      estimates. Through simulation, we assess the finite-sample properties of our
      estimators and consider other possible sampling designs for our examples that
      could have further improved statistical efficiency. To help promote subsampling
      designs, our R package CompareTests computes all of our agreement and diagnostic
      accuracy statistics.

PMID- 22139833
TI  - Bioinformatic and mutational analysis of channelrhodopsin-2 protein cation
      conducting pathway.
AB  - Channelrhodopsin-2 (ChR2) is a light-gated cation channel widely used as a
      biotechnological tool to control membrane depolarization in various cell types
      and tissues. Although several ChR2 variants with modified properties have been
      generated, the structural determinants of the protein function are largely
      unresolved. We used bioinformatic modeling of the ChR2 structure to identify the
      putative cationic pathway within the channel, which is formed by a system of
      inner cavities that are uniquely present in this microbial rhodopsin. Site
      directed mutagenesis combined with patch clamp analysis in HeLa cells was used to
      determine key residues involved in ChR2 conductance and selectivity. Among them,
      Gln-56 is important for ion conductance, whereas Ser-63, Thr-250, and Asn-258 are
      previously unrecognized residues involved in ion selectivity and photocurrent
      kinetics. This study widens the current structural information on ChR2 and can
      assist in the design of new improved variants for specific biological
      applications.

PMID- 22139834
TI  - Substrate binding in protein-tyrosine phosphatase-like inositol polyphosphatases.
AB  - Protein-tyrosine phosphatase-like inositol polyphosphatases are microbial enzymes
      that catalyze the stepwise removal of one or more phosphates from highly
      phosphorylated myo-inositols via a relatively ordered pathway. To understand the
      substrate specificity and kinetic mechanism of these enzymes we have determined
      high resolution, single crystal, x-ray crystallographic structures of inactive
      Selenomonas ruminantium PhyA in complex with myo-inositol hexa- and
      pentakisphosphate. These structures provide the first glimpse of a myo-inositol
      polyphosphatase-ligand complex consistent with its known specificity and reveal
      novel features of the kinetic mechanism. To complement the structural studies,
      fluorescent binding assays have been developed and demonstrate that the K(d) for
      this enzyme is several orders of magnitude lower than the K(m). Together with
      rapid kinetics data, these results suggest that the protein tyrosine phosphatase
      like inositol polyphosphatases have a two-step, substrate-binding mechanism that
      facilitates catalysis.

PMID- 22139835
TI  - Identification of interaction sites for dimerization and adapter recruitment in
      Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 4.
AB  - Toll-like receptor signaling requires interactions of the Toll/IL-1 receptor
      (TIR) domains of the receptor and adapter proteins. Using the mammalian protein
      protein interaction trap strategy, homology modeling, and site-directed
      mutagenesis, we identify the interaction surfaces in the TLR4 TIR domain for the
      TLR4-TLR4, TLR4-MyD88 adapter-like (MAL), and TLR4-TRIF-related adapter molecule
      (TRAM) interaction. Two binding sites are equally important for TLR4 dimerization
      and adapter recruitment. In a model based on the crystal structure of the dimeric
      TLR10 TIR domain, the first binding site mediates TLR4-TLR4 TIR-TIR interaction.
      Upon dimerization, two identical second binding sites of the TLR4 TIR domain are
      juxtaposed and form an extended binding platform for both MAL and TRAM. In our
      mammalian protein-protein interaction trap assay, MAL and TRAM compete for
      binding to this platform. Our data suggest that adapter binding can stabilize the
      TLR4 TIR dimerization.

PMID- 22139836
TI  - Sublethal doses of beta-amyloid peptide abrogate DNA-dependent protein kinase
      activity.
AB  - Accumulation of DNA damage and deficiency in DNA repair potentially contribute to
      the progressive neuronal loss in neurodegenerative disorders, including Alzheimer
      disease (AD). In multicellular eukaryotes, double strand breaks (DSBs), the most
      lethal form of DNA damage, are mainly repaired by the nonhomologous end joining
      pathway, which relies on DNA-PK complex activity. Both the presence of DSBs and a
      decreased end joining activity have been reported in AD brains, but the molecular
      player causing DNA repair dysfunction is still undetermined. beta-Amyloid
      (Abeta), a potential proximate effector of neurotoxicity in AD, might exert
      cytotoxic effects by reactive oxygen species generation and oxidative stress
      induction, which may then cause DNA damage. Here, we show that in PC12 cells
      sublethal concentrations of aggregated Abeta(25-35) inhibit DNA-PK kinase
      activity, compromising DSB repair and sensitizing cells to nonlethal oxidative
      injury. The inhibition of DNA-PK activity is associated with down-regulation of
      the catalytic subunit DNA-PK (DNA-PKcs) protein levels, caused by oxidative
      stress and reversed by antioxidant treatment. Moreover, we show that sublethal
      doses of Abeta(1-42) oligomers enter the nucleus of PC12 cells, accumulate as
      insoluble oligomeric species, and reduce DNA-PK kinase activity, although in the
      absence of oxidative stress. Overall, these findings suggest that Abeta mediates
      inhibition of the DNA-PK-dependent nonhomologous end joining pathway contributing
      to the accumulation of DSBs that, if not efficiently repaired, may lead to the
      neuronal loss observed in AD.

PMID- 22139837
TI  - Androgen Receptor Enhances p27 Degradation in Prostate Cancer Cells through Rapid
      and Selective TORC2 Activation.
AB  - Androgen receptor (AR) plays a central role in prostate cancer (PCa) growth, with
      androgen deprivation or AR down-regulation causing cell-cycle arrest and
      accumulation of the p27 cyclin-dependent kinase inhibitor. The molecular basis
      for this AR regulation of cell-cycle progression remains unclear. Here we
      demonstrate that androgen can rapidly reduce p27 protein in PCa cells by
      increasing its proteasome-mediated degradation. This rapid androgen-stimulated
      p27 degradation was mediated by AKT through the phosphorylation of p27 T157.
      Significantly, androgen increased TORC2-mediated AKT S473 phosphorylation without
      affecting the PDK1-mediated AKT T308 phosphorylation or TORC1 activity. The TORC2
      activation was further supported by enhanced mTOR/RICTOR association and
      increased phosphorylation of additional TORC2 substrates, SGK1 and PKCalpha. The
      androgen-stimulated nuclear translocation of AR was associated with markedly
      increased nuclear SIN1, a critical component of TORC2. Finally, the androgen
      mediated TORC2/AKT activation targets a subset of AKT substrates including p27
      and FOXO1, but not PRAS40. This study reveals a pathway linking AR to a selective
      activation of TORC2, the subsequent activation of AKT, and phosphorylation of a
      discrete set of AKT substrates that regulate cellular proliferation and survival.
      These findings establish that TORC2 can function as a central regulator of growth
      in response to signals that are distinct from those regulating TORC1, and support
      efforts to target TORC2 for cancer therapy.

PMID- 22139838
TI  - Novel mechanistic link between focal adhesion remodeling and glucose-stimulated
      insulin secretion.
AB  - Actin cytoskeleton remodeling is well known to be positively involved in glucose
      stimulated pancreatic beta cell insulin secretion. We have observed glucose
      stimulated focal adhesion remodeling at the beta cell surface and have shown this
      to be crucial for glucose-stimulated insulin secretion. However, the mechanistic
      link between such remodeling and the insulin secretory machinery remained unknown
      and was the major aim of this study. MIN6B1 cells, a previously validated model
      of primary beta cell function, were used for all experiments. Total internal
      reflection fluorescence microscopy revealed the glucose-responsive co
      localization of focal adhesion kinase (FAK) and paxillin with integrin beta1 at
      the basal cell surface after short term stimulation. In addition, blockade of the
      interaction between beta1 integrins and the extracellular matrix with an anti
      beta1 integrin antibody (Ha2/5) inhibited short term glucose-induced
      phosphorylation of FAK (Tyr-397), paxillin (Tyr-118), and ERK1/2 (Thr-202/Tyr
      204). Pharmacological inhibition of FAK activity blocked glucose-induced actin
      cytoskeleton remodeling and glucose-induced disruption of the F-actin/SNAP-25
      association at the plasma membrane as well as the distribution of insulin
      granules to regions in close proximity to the plasma membrane. Furthermore, FAK
      inhibition also completely blocked short term glucose-induced activation of the
      Akt/AS160 signaling pathway. In conclusion, these results indicate 1) that
      glucose-induced activation of FAK, paxillin, and ERK1/2 is mediated by beta1
      integrin intracellular signaling, 2) a mechanism whereby FAK mediates glucose
      induced actin cytoskeleton remodeling, hence allowing docking and fusion of
      insulin granules to the plasma membrane, and 3) a possible functional role for
      the Akt/AS160 signaling pathway in the FAK-mediated regulation of glucose
      stimulated insulin secretion.

PMID- 22139839
TI  - miR-125b and miR-155 contribute to BCL2 repression and proliferation in response
      to CD40 ligand (CD154) in human leukemic B-cells.
AB  - Developmental stage-specific regulation of BCL2 occurs during B-cell maturation
      and has a role in normal immunity. CD40 signaling promotes proliferation and
      rescues B-cells from apoptosis, partly through induction of BCL2L1 and BCL2A1 and
      repression of BCL2. We previously showed that a stromal cell/CD40 ligand (CD154)
      culture system reproduced this switch in survival protein expression in primary
      human leukemic B-cells and we employed this model system to investigate BCL2
      repression. BCL2 was post-transcriptionally regulated and the repressed BCL2 mRNA
      was associated with non-polysomal, but dense fractions on sucrose density
      gradients. Microarrays identified a set of miRNA that were induced by culture
      conditions and potentially able to bind to the BCL2 3'-UTR. Luciferase reporter
      assays demonstrated that miR-125b and miR-155 repressed BCL2 mRNA but while
      stromal cell contact alone was sufficient to induce strongly miR-125b this did
      not cause BCL2 repression. miR-155, which is the most abundant miRNA under basal
      conditions, specifically required CD154 for further induction above a threshold
      to exert its full repressive effects. Anti-miR-125b and anti-miR-155 prevented
      CD154-mediated repression of BCL2 and reduced CD154-mediated proliferation in the
      MEC1 B-cell line. We suggest that miR-155 and miR-125b, which are induced by
      CD154 and stromal cell signals, contribute to regulating proliferation and that
      BCL2 is one of their target mRNAs.

PMID- 22139840
TI  - Gene dose influences cellular and calcium channel dysregulation in heterozygous
      and homozygous T4826I-RYR1 malignant hyperthermia-susceptible muscle.
AB  - Malignant hyperthermia susceptibility (MHS) is primarily conferred by mutations
      within ryanodine receptor type 1 (RYR1). Here we address how the MHS mutation
      T4826I within the S4-S5 linker influences excitation-contraction coupling and
      resting myoplasmic Ca(2+) concentration ([Ca(2+)](rest)) in flexor digitorum
      brevis (FDB) and vastus lateralis prepared from heterozygous (Het) and homozygous
      (Hom) T4826I-RYR1 knock-in mice (Yuen, B. T., Boncompagni, S., Feng, W., Yang,
      T., Lopez, J. R., Matthaei, K. I., Goth, S. R., Protasi, F., Franzini-Armstrong,
      C., Allen, P. D., and Pessah, I. N. (2011) FASEB J. doi:22131268). FDB responses
      to electrical stimuli and acute halothane (0.1%, v/v) exposure showed a rank
      order of Hom ? Het ? WT. Release of Ca(2+) from the sarcoplasmic reticulum and
      Ca(2+) entry contributed to halothane-triggered increases in [Ca(2+)](rest) in
      Hom FDBs and elicited pronounced Ca(2+) oscillations in ~30% of FDBs tested.
      Genotype contributed significantly elevated [Ca(2+)](rest) (Hom > Het > WT)
      measured in vivo using ion-selective microelectrodes. Het and Hom oxygen
      consumption rates measured in intact myotubes using the Seahorse Bioscience
      (Billerica, MA) flux analyzer and mitochondrial content measured with MitoTracker
      were lower than WT, whereas total cellular calpain activity was higher than WT.
      Muscle membranes did not differ in RYR1 expression nor in Ser(2844)
      phosphorylation among the genotypes. Single channel analysis showed highly
      divergent gating behavior with Hom and WT favoring open and closed states,
      respectively, whereas Het exhibited heterogeneous gating behaviors.
      [(3)H]Ryanodine binding analysis revealed a gene dose influence on binding
      density and regulation by Ca(2+), Mg(2+), and temperature. Pronounced
      abnormalities inherent in T4826I-RYR1 channels confer MHS and promote basal
      disturbances of excitation-contraction coupling, [Ca(2+)](rest), and oxygen
      consumption rates. Considering that both Het and Hom T4826I-RYR1 mice are viable,
      the remarkable isolated single channel dysfunction mediated through this mutation
      in S4-S5 cytoplasmic linker must be highly regulated in vivo.

PMID- 22139841
TI  - Molecular basis for the association of microcephalin (MCPH1) protein with the
      cell division cycle protein 27 (Cdc27) subunit of the anaphase-promoting complex.
AB  - Microcephalin (MCPH1), the first gene identified as causative for primary
      recessive autosomal microcephaly, is aberrantly expressed in autism-like
      disorders and human malignancy of breast and ovarian origin. MCPH1, the encoded
      protein product, has been implicated in various cellular processes including the
      DNA damage checkpoint, DNA repair, and transcription. Although our understanding
      of the cellular context in which MCPH1 operates continues to develop, a
      structural understanding of the C-terminal tandem BRCT domains of MCPH1 remains
      unexplored. Here, we identify cell division cycle protein 27 (Cdc27), a component
      of the anaphase-promoting complex (APC/C), as a novel interacting partner of
      MCPH1. We provide in vitro and in vivo evidence that the C-terminal tandem BRCT
      domains of MCPH1 (C-BRCTs) bind Cdc27 in a phosphorylation-dependent manner. To
      characterize this interaction further, we determined the structure of MCPH1 C
      BRCTs in complex with a phosphorylated Cdc27 peptide (pCdc27) using x-ray
      crystallography. Based on this structure, we identified single amino acid
      mutations targeted at the binding interface that disrupted the MCPH1-pCdc27
      interaction. Collectively, our data define the biochemical, structural, and
      cellular determinants of the novel interaction between MCPH1 and Cdc27 and
      suggest that this interaction may occur within the larger context of MCPH1-APC/C.

PMID- 22139842
TI  - Importance of N- and C-terminal regions of IbpA, Escherichia coli small heat
      shock protein, for chaperone function and oligomerization.
AB  - Small heat shock proteins are ubiquitous molecular chaperones that, during
      cellular stress, bind to misfolded proteins and maintain them in a refolding
      competent state. Two members of the small heat shock protein family, IbpA and
      IbpB, are present in Escherichia coli. Despite 48% sequence identity, the
      proteins have distinct activities in promoting protein disaggregation.
      Cooperation between IbpA and IbpB is crucial for prevention of the irreversible
      aggregation of proteins. In this study, we investigated the importance of the N-
      and C-terminal regions of IbpA for self-oligomerization and chaperone functions.
      Deletion of either the N- or C-terminal region of IbpA resulted in a defect in
      the IbpA fibril formation process. The deletions also impaired IbpA chaperone
      function, defined as the ability to stabilize, in cooperation with IbpB, protein
      aggregates in a disaggregation-competent state. Our results show that the defect
      in chaperone function, observed in truncated versions of IbpA, is due to the
      inability of these proteins to interact with substrate proteins and consequently
      to change the properties of aggregates. At the same time, these versions of IbpA
      interact with IbpB similarly to the wild type protein. Competition experiments
      performed with the pC peptide, which corresponds to the IbpA C terminus,
      suggested the importance of IbpA intermolecular interactions in the stabilization
      of aggregates in a state competent for disaggregation. Our results suggest that
      these interactions are not only dependent on the universally conserved IEI motif
      but also on arginine 133 neighboring the IEI motif. IbpA mutated at arginine 133
      to alanine lacked chaperone activity.

PMID- 22139843
TI  - Activation of Akt, not connexin 43 protein ubiquitination, regulates gap junction
      stability.
AB  - The pore-forming gap junctional protein connexin 43 (Cx43) has a short (1-3 h)
      half-life in cells in tissue culture and in whole tissues. Although critical for
      cellular function in all tissues, the process of gap junction turnover is not
      well understood because treatment of cells with a proteasomal inhibitor results
      in larger gap junctions but little change in total Cx43 protein whereas lysosomal
      inhibitors increase total, mostly nonjunctional Cx43. To better understand
      turnover and identify potential sites of Cx43 ubiquitination, we prepared
      constructs of Cx43 with different lysines converted to arginines. However, when
      transfected into cells, a mutant version of Cx43 with all lysines converted to
      arginines behaved similarly to wild type in the presence of proteasomal and
      lysosomal inhibitors, indicating that ubiquitination of Cx43 did not appear to be
      playing a role in gap junction stability. Through the use of inhibitors and
      dominant negative constructs, we found that Akt (protein kinase B) activity
      controlled gap junction stability and was necessary to form larger stable gap
      junctions. Akt activation was increased upon proteasomal inhibition and resulted
      in phosphorylation of Cx43 at Akt phosphorylation consensus sites. Thus, we
      conclude that Cx43 ubiquitination is not necessary for the regulation of Cx43
      turnover; rather, Akt activity, probably through direct phosphorylation of Cx43,
      controls gap junction stability. This linkage of a kinase involved in controlling
      cell survival and growth to gap junction stability may mechanistically explain
      how gap junctions and Akt play similar regulatory roles.

PMID- 22139844
TI  - Critical role for heat shock protein 20 (HSP20) in migration of malarial
      sporozoites.
AB  - Plasmodium sporozoites, single cell eukaryotic pathogens, use their own
      actin/myosin-based motor machinery for life cycle progression, which includes
      forward locomotion, penetration of cellular barriers, and invasion of target
      cells. To display fast gliding motility, the parasite uses a high turnover of
      actin polymerization and adhesion sites. Paradoxically, only a few classic actin
      regulatory proteins appear to be encoded in the Plasmodium genome. Small heat
      shock proteins have been associated with cytoskeleton modulation in various
      biological processes. In this study, we identify HSP20 as a novel player in
      Plasmodium motility and provide molecular genetics evidence for a critical role
      of a small heat shock protein in cell traction and motility. We demonstrate that
      HSP20 ablation profoundly affects sporozoite-substrate adhesion, which translates
      into aberrant speed and directionality in vitro. Loss of HSP20 function impairs
      migration in the host, an important sporozoite trait required to find a blood
      vessel and reach the liver after being deposited in the skin by the mosquito. Our
      study also shows that fast locomotion of sporozoites is crucial during natural
      malaria transmission.

PMID- 22139846
TI  - Metal selectivity determinants in a family of transition metal transporters.
AB  - Metal tolerance proteins (MTPs) are plant members of the cation diffusion
      facilitator (CDF) transporter family involved in cellular metal homeostasis.
      Members of the CDF family are ubiquitously found in all living entities and show
      principal selectivity for Zn(2+), Mn(2+), and Fe(2+). Little is known regarding
      metal selectivity determinants of CDFs. We identified a novel cereal member of
      CDFs in barley, termed HvMTP1, that localizes to the vacuolar membrane. Unlike
      its close relative AtMTP1, which is highly selective for Zn(2+), HvMTP1 exhibits
      selectivity for both Zn(2+) and Co(2+) as assessed by its ability to suppress
      yeast mutant phenotypes for both metals. Expression of HvMTP1/AtMTP1 chimeras in
      yeast revealed a five-residue sequence within the AtMTP1 N-segment of the His
      rich intracytoplasmic loop that confines specificity to Zn(2+). Furthermore,
      mutants of AtMTP1 generated through random mutagenesis revealed residues embedded
      within transmembrane domain 3 that additionally specify the high degree of Zn(2+)
      selectivity. We propose that the His-rich loop, which might play a role as a zinc
      chaperone, determines the identity of the metal ions that are transported. The
      residues within transmembrane domain 3 can also influence metal selectivity,
      possibly through conformational changes induced at the cation transport site
      located within the membrane or at the cytoplasmic C-terminal domain.

PMID- 22139845
TI  - The p65 subunit of NF-kappaB inhibits COL1A1 gene transcription in human dermal
      and scleroderma fibroblasts through its recruitment on promoter by protein
      interaction with transcriptional activators (c-Krox, Sp1, and Sp3).
AB  - Transcriptional mechanisms regulating type I collagen genes expression in
      physiopathological situations are not completely known. In this study, we have
      investigated the role of nuclear factor-kappaB (NF-kappaB) transcription factor
      on type I collagen expression in adult normal human (ANF) and scleroderma (SF)
      fibroblasts. We demonstrated that NF-kappaB, a master transcription factor
      playing a major role in immune response/apoptosis, down-regulates COL1A1
      expression by a transcriptional control involving the -112/-61 bp sequence. This
      51-bp region mediates the action of two zinc fingers, Sp1 (specific protein-1)
      and Sp3, acting as trans-activators of type I collagen expression in ANF and SF.
      Knockdown of each one of these trans factors by siRNA confirmed the trans
      activating effect of Sp1/Sp3 and the p65 subunit of NF-kappaB trans-inhibiting
      effect on COL1A1 expression. Despite no existing kappaB consensus sequence in the
      COL1A1 promoter, we found that Sp1/Sp3/c-Krox and NF-kappaB bind and/or are
      recruited on the proximal promoter in chromatin immunoprecipitation (ChIP)
      assays. Attempts to elucidate whether interactions between Sp1/Sp3/c-Krox and p65
      are necessary to mediate the NF-kappaB inhibitory effect on COL1A1 in ANF and SF
      were carried out; in this regard, immunoprecipitation assays revealed that they
      interact, and this was validated by re-ChIP. Finally, the knockdown of Sp1/Sp3/c
      Krox prevents the p65 inhibitory effect on COL1A1 transcription in ANF, whereas
      only the siRNAs targeting Sp3 and c-Krox provoked the same effect in SF,
      suggesting that particular interactions are characteristic of the scleroderma
      phenotype. In conclusion, our findings highlight a new mechanism for COL1A1
      transcriptional regulation by NF-kappaB, and these data could allow the
      development of new antifibrotic strategies.

PMID- 22139848
TI  - Mendelian inheritance by eye.

PMID- 22139847
TI  - p38alpha mediates cell survival in response to oxidative stress via induction of
      antioxidant genes: effect on the p70S6K pathway.
AB  - We reveal a novel pro-survival role for mammalian p38alpha in response to
      H(2)O(2), which involves an up-regulation of antioxidant defenses. The presence
      of p38alpha increases basal and H(2)O(2)-induced expression of the antioxidant
      enzymes: superoxide-dismutase 1 (SOD-1), SOD-2, and catalase through different
      mechanisms, which protects from reactive oxygen species (ROS) accumulation and
      prevents cell death. p38alpha was found to regulate (i) H(2)O(2)-induced SOD-2
      expression through a direct regulation of transcription mediated by activating
      transcription factor 2 (ATF-2) and (ii) H(2)O(2)-induced catalase expression
      through regulation of protein stability and mRNA expression and/or stabilization.
      As a consequence, SOD and catalase activities are higher in WT MEFs. We also
      found that this p38alpha-dependent antioxidant response allows WT cells to
      maintain an efficient activation of the mTOR/p70S6K pathway. Accordingly, the
      loss of p38alpha leads to ROS accumulation in response to H(2)O(2), which causes
      cell death and inactivation of mTOR/p70S6K signaling. This can be rescued by
      either p38alpha re-expression or treatment with the antioxidants, N-acetyl
      cysteine, or exogenously added catalase. Therefore, our results reveal a novel
      homeostatic role for p38alpha in response to oxidative stress, where ROS removal
      is favored by antioxidant enzymes up-regulation, allowing cell survival and
      mTOR/p70S6K activation.

PMID- 22139849
TI  - Confirmatory factor analysis of the Sexual Adjustment and Body Image Scale in
      women with gynecologic cancer.
AB  - BACKGROUND: There is evidence that treatment of gynecologic cancer (GC)
      negatively affects body image and sexuality. The Sexual Adjustment and Body Image
      Scale (SABIS-G) was developed to assess disturbances after diagnosis of GC. The
      objective of this study was to confirm the factor structure using a confirmatory
      factor analysis (CFA). METHODS: Women with a history of GC completed the SABIS-G,
      a 9-item self-report measure. Ninety randomly selected participants were used for
      the exploratory factor analysis (EFA). CFA was performed on the remaining
      participants (n = 204) to confirm the factor structure developed in the EFA
      against a one-factor model. Test-retest reliability between baseline and follow
      up scores was assessed using the intraclass correlation coefficient. RESULTS: A
      total of 614 eligible patients were approached to participate: 398 (65%)
      consented to the study and 294 (74%) completed the SABIS-G. The median age was 53
      years (range, 27-80 years) and the primary site of disease was: 120 (41%)
      uterine, 85 (29%) ovary, 82 (28%) cervix, and 7 (2%) other. A 2-factor structure
      was favored in the EFA, and the CFA fit indices indicated an excellent fit for
      the 2-factor measurement model (standardized root-mean-square residual = 0.05,
      non-normed fit index = 0.97, comparative fit index = 0.98). Internal consistency
      reliability was high for the Body Image (0.88) and Sexual Adjustment (0.91)
      subscales, as was test-retest reliability (0.89). CONCLUSIONS: These results
      confirm the 2-factor structure of the SABIS-G and provide evidence that this is a
      valid and reliable instrument to measure changes in body image and sexuality in
      women after a diagnosis of GC.

PMID- 22139850
TI  - Metaparenting: associations with parenting stress, child-rearing practices, and
      retention in parents of children at risk for ADHD.
AB  - The aim of the study is to investigate metaparenting (effortful, deliberate
      cognition about parenting) in parents of children at risk for ADHD including
      predictors, correlates, and intervention outcomes. Parents (n = 68) of children
      with significant ADHD symptoms (i.e., >= 6 inattentive or hyperactive/impulsive
      symptoms with impairment in >= 2 settings, mostly un-medicated) provided ratings
      of metaparenting, parenting stress and practices, and child ADHD symptoms before
      and after parent training. Parents were predominantly Caucasian, in their upper
      thirties, and most had schooling beyond high school. We investigated the relation
      between metaparenting and baseline predictors, and whether metaparenting
      predicted (1) parenting behaviors at baseline, (2) attrition, and (3) parenting
      stress and parent/child behaviors at outcome. More educated mothers, with fewer
      people living in the home, and higher levels of parenting stress, reported more
      metaparenting. Parents with lower problem-solving and assessing scores reported
      more inconsistent parenting, and those with lower problem-solving scores were
      more likely to drop out of parent training. Higher problem-solving and reflecting
      scores at baseline were associated with more parental stress. Higher reflecting
      at baseline predicted child hyperactivity/impulsivity at outcome. Our findings
      indicate metaparenting is associated with parenting behaviors and decisions to
      complete parent training. Furthermore, metaparenting appears to be a complex,
      finely nuanced construct with both positive and negative associations with
      reports of parenting practices and stress.

PMID- 22139851
TI  - The prevalence of HLA-B27 in the US: data from the US National Health and
      Nutrition Examination Survey, 2009.
AB  - OBJECTIVE: To carry out the first large-scale population study of the prevalence
      of HLA-B27 in the US, which is needed for public health planning purposes because
      of recent improvements in medical therapy and diagnostic testing for ankylosing
      spondylitis (AS). METHODS: The national prevalence of HLA-B27 was determined as
      part of the 2009 US National Health and Nutrition Examination Survey (NHANES), a
      cross-sectional survey monitoring the health and nutritional status of the US
      civilian, noninstitutionalized population. DNA polymerase chain reaction analysis
      was conducted in samples from 2,320 adults ages 20-69 years from this nationally
      representative sample. RESULTS: The age-adjusted US prevalence of B27 was 6.1%
      (95% confidence interval [95% CI] 4.6-8.2). By race/ethnicity, the prevalence of
      B27 was 7.5% (95% CI 5.3-10.4) among non-Hispanic whites and 3.5% (95% CI 2.5
      4.8) among all other US races/ethnicities combined. In Mexican Americans, the
      prevalence was 4.6% (95% CI 3.4-6.1). The prevalence of B27 could not be reliably
      estimated for other US racial/ethnic groups because of the low number of B27
      positive individuals in those groups. For adults 50-69 years of age, the
      prevalence of B27 was 3.6% (95% CI 2.2-5.8), which suggested a decrease in B27
      with age. These prevalence estimates took into account the NHANES survey design
      and are reviewed with respect to data from the medical literature. CONCLUSION:
      Our findings provide the first US national prevalence estimates for HLA-B27. A
      decline in the prevalence of HLA-B27 with age is suggested by these data but must
      be confirmed by additional studies.

PMID- 22139853
TI  - An eXpert AFB smear?

PMID- 22139854
TI  - The use of an automated quantitative polymerase chain reaction (Xpert MTB/RIF) to
      predict the sputum smear status of tuberculosis patients.
AB  - Xpert MTB/RIF-generated cycle-threshold (C(T)) values have poor clinical utility
      as a rule-in test for smear positivity (cut-point <=20.2; sensitivity 32.3%,
      specificity 97.1%) but moderately good rule-out value (cut-point >31.8; negative
      predictive value 80.0%). Thus, 20% of individuals with C(T) values >31.8 were
      erroneously ruled out as smear-negative. This group had a significantly lower
      sputum bacillary load relative to correctly classified smear-positive patients
      (C(T) <= 31.8; P < .001). These data inform on public health and contact tracing
      strategies.

PMID- 22139852
TI  - Interleukin 10 in the tumor microenvironment: a target for anticancer
      immunotherapy.
AB  - IL-10 is an immunomodulatory cytokine that is frequently upregulated in various
      types of cancer. The biological role of IL-10 in cancer is quite complex;
      however, the presence of IL-10 in advanced metastases and the positive
      correlation between serum IL-10 levels and progression of disease indicates a
      critical role of IL-10 in the tumor microenvironment. IL-10 has been shown to
      directly affect the function of antigen-presenting cells by inhibiting the
      expression of MHC and costimulatory molecules, which in turn induces immune
      suppression or tolerance. Additionally, IL-10 downregulates the expression of Th1
      cytokines and induces T-regulatory responses. Taken together, a combination of IL
      10 antagonism and immunostimulatory treatments such as cancer vaccines, Toll-like
      receptor agonists, Th1 cytokines, and chemokines would be a logical approach to
      enhance an antitumor immune response.

PMID- 22139855
TI  - On chirality transfer in electron donor-acceptor complexes. A prediction for the
      sulfinimine...BF3 system.
AB  - Stabilization energies of the electron donor-acceptor sulfinimine...BF(3)
      complexes calculated at either the B3LYP/aug-cc-pVTZ or the MP2/aug-cc-pVTZ level
      do not allow to judge, whether the N- or O-atom in sulfinimine is stronger
      electron-donor to BF(3) . The problem seems to be solvable because chirality
      transfer phenomenon between chiral sulfinimine and achiral BF(3) is expected to
      be vibrational circular dichroism (VCD) active. Moreover, the bands associated
      with the achiral BF(3) molecule are predicted to be the most intense in the
      entire spectrum. However, the VCD band robustness analyses show that most of the
      chirality transfer modes of BF(3) are unreliable. Conversely, variation of VCD
      intensity with change of intermolecular distance, angle, and selected dihedrals
      between the complex partners shows that to establish the robustness of chirality
      transfer mode. It is also necessary to determine the influence of the potential
      energy surface (PES) shape on the VCD intensity. At the moment, there is still no
      universal criterion for the chirality transfer mode robustness and the
      conclusions formulated based on one system cannot be directly transferred even to
      a quite similar one. However, it is certain that more attention should be focused
      on relation of PES shape and the VCD mode robustness problem.

PMID- 22139856
TI  - Hypokalemia-induced T-U fusion.

PMID- 22139857
TI  - Palladium-catalyzed carbonylative alpha-arylation for accessing 1,3-diketones.

PMID- 22139859
TI  - News from the pit lane.

PMID- 22139858
TI  - A parallel imaging approach to wide-field MR microscopy.
AB  - Magnetic resonance microscopy, suggested in the earliest papers on MRI, has
      always been limited by the low signal-to-noise ratio resulting from the small
      voxel size. Magnetic resonance microscopy has largely been enabled by the use of
      microcoils that provide the signal-to-noise ratio improvement required to
      overcome this limitation. Concomitant with the small coils is a small field-of
      view, which limits the use of magnetic resonance microscopy as a histological
      tool or for imaging large regions in general. This article describes initial
      results in wide field-of-view magnetic resonance microscopy using a large array
      of narrow, parallel coils, which provides a signal-to-noise ratio enhancement as
      well as the ability to use parallel imaging techniques. Comparison images made
      between a volume coil and the proposed technique demonstrate reductions in
      imaging time of more than 100 with no loss in signal-to-noise ratio or
      resolution.

PMID- 22139860
TI  - Estimating net transition probabilities from cross-sectional data with
      application to risk factors in chronic disease modeling.
AB  - A problem occurring in chronic disease modeling is the estimation of transition
      probabilities of moving from one state of a categorical risk factor to another.
      Transitions could be obtained from a cohort study, but often such data may not be
      available. However, under the assumption that transitions remain stable over
      time, age specific cross-sectional prevalence data could be used instead.
      Problems that then arise are parameter identifiability and the fact that age
      dependent cross-sectional data are often noisy or are given in age intervals. In
      this paper we propose a method to estimate so-called net annual transition
      probabilities from cross-sectional data, including their uncertainties. Net
      transitions only describe the net inflow or outflow into a certain risk factor
      state at a certain age. Our approach consists of two steps: first, smooth the
      data using multinomial P-splines, second, from these data estimate net transition
      probabilities. This second step can be formulated as a transportation problem,
      which is solved using the simplex algorithm from linear programming theory. A
      sensible specification of the cost matrix is crucial to get meaningful results.
      Uncertainties are assessed by parametric bootstrapping. We illustrate our method
      using data on body mass index. We conclude that this method provides a flexible
      way of estimating net transitions and that the use of net transitions has
      implications for model dynamics, for example when modeling interventions.

PMID- 22139861
TI  - Use of Tetrabenazine in Huntington Disease Patients on Antidepressants or with
      Advanced Disease: Results from the TETRA-HD Study.
AB  - The safety and effectiveness of tetrabenazine in different sub-populations of
      Huntington disease (HD) is not known. In this study, we evaluated the safety of
      tetrabenazine in individuals on an antidepressant and its effectiveness in
      advanced HD. Tetrabenazine was not associated with an increased incidence of
      depressed mood among those taking antidepressants and was effective at reducing
      chorea in those with advanced HD.

PMID- 22139864
TI  - Prospective assessment of outcomes in 411 patients treated with hyperbaric oxygen
      for chronic radiation tissue injury.
AB  - BACKGROUND: Although hyperbaric oxygen is used to treat chronic radiation tissue
      injury, clinical evidence supporting its efficacy has been limited to date. The
      authors report prospectively collected patient outcomes from a single center's
      large experience using hyperbaric oxygen to treat chronic radiation injury.
      METHODS: Since 2002, patient outcomes at the conclusion of a course of hyperbaric
      oxygen treatment for chronic radiation tissue injury at Virginia Mason Medical
      Center in Seattle have been graded by a board-certified hyperbaric physician and
      prospectively recorded. From 2002 to 2010, a total of 525 patients received
      treatment for 1 of 6 forms of radionecrosis analyzed. After excluding 114
      patients for incomplete records or treatment courses or for previous receipt of
      hyperbaric oxygen therapy, records of 411 patients were retrospectively reviewed
      in 2010, and outcomes were regraded by a second board-certified physician. A
      positive clinical response was defined as an outcome graded as either "resolved"
      (90%-100% improved) or "significantly improved" (50%-89% improved). RESULTS: A
      positive outcome from hyperbaric treatment occurred in 94% of patients with
      osteoradionecrosis of the jaw (n = 43), 76% of patients with cutaneous
      radionecrosis that caused open wounds (n = 58), 82% of patients with laryngeal
      radionecrosis (n = 27), 89% of patients with radiation cystitis (n = 44), 63% of
      patients with gastrointestinal radionecrosis (n = 73), and 100% of patients who
      were treated in conjunction with oral surgery in a previously irradiated jaw (n =
      166). CONCLUSIONS: The outcomes of 411 patients collected prospectively over 8
      years strongly supported the efficacy of hyperbaric oxygen treatment for the 6
      conditions evaluated. The response rates previously reported in numerous small
      series were supported by the responses achieved in this large, single-center
      experience.

PMID- 22139866
TI  - Birth control vaccine targeting leukemia inhibitory factor.
AB  - The population explosion and unintended pregnancies resulting in elective
      abortions continue to impose major public health issues. This calls for a better
      method of contraception. Immunocontraception has been proposed as a valuable
      alternative that can fulfill most, if not all, of the properties of an ideal
      contraceptive. There are several targets that are being explored for
      contraceptive vaccine development. Leukemia inhibitory factor (LIF), a member of
      interleukin-6 family, is required for embryo development and successful
      blastocyst implantation in several mammalian species. The present study was
      conducted to examine if LIF can be a target for the development of a birth
      control vaccine. Three sequences from LIF and two sequences from LIF-receptor
      (LIF-R) that span the regions involved in ligand-receptor binding were
      delineated, and peptides were synthesized based upon these sequences. Antibodies
      raised against these five peptides reduced LIF bioactivity in an in vitro culture
      assay using BA/F3 mLIF-R-mpg130 cells. Vaccines were prepared by conjugating
      these peptides to various carrier proteins. Immunization of female mice with
      these peptide vaccines induced a long-lasting, circulating as well as local
      antibody response in various parts of the genital tract, and resulted in a
      significant (P <= 0.05) inhibition in fertility in all the three trials; the LIF
      R peptide vaccines proved to be a better vaccine target. The data indicate that
      LIF/LIF-R is an excellent target for the development of a birth control vaccine.
      This is the first study, to our knowledge, that examined LIF/LIF-R as a target
      for immunocontraception. The findings of this study can be easily translated to
      humans since LIF/LIF-R is also important for implantation and pregnancy in women.

PMID- 22139865
TI  - Resolution of inflammation induces osteoblast function and regulates the Wnt
      signaling pathway.
AB  - OBJECTIVE: Inflammation in the bone microenvironment stimulates osteoclast
      differentiation, resulting in uncoupling of resorption and formation. Mechanisms
      contributing to the inhibition of osteoblast function in inflammatory diseases,
      however, have not been elucidated. Rheumatoid arthritis (RA) is a prototype of an
      inflammatory arthritis that results in focal loss of articular bone. The paucity
      of bone repair in inflammatory diseases such as RA raises compelling questions
      regarding the impact of inflammation on bone formation. The aim of this study was
      to establish the mechanisms by which inflammation regulates osteoblast activity.
      METHODS: We characterized an innovative variant of a murine model of arthritis in
      which inflammation is induced in C57BL/6J mice by transfer of arthritogenic K/BxN
      serum and allowed to resolve. RESULTS: In the setting of resolving inflammation,
      bone resorption ceased and appositional osteoblast-mediated bone formation was
      induced, resulting in repair of eroded bone. Resolution of inflammation was
      accompanied by striking changes in the expression of regulators of the Wnt/beta
      catenin pathway, which is critical for osteoblast differentiation and function.
      Down-regulation of the Wnt antagonists secreted frizzled-related protein 1
      (sFRP1) and sFRP2 during the resolution phase paralleled induction of the
      anabolic and pro-matrix mineralization factors Wnt10b and DKK2, demonstrating the
      role of inflammation in regulating Wnt signaling. CONCLUSION: Repair of articular
      bone erosion occurs in the setting of resolving inflammation, accompanied by
      alterations in the Wnt signaling pathway. These data imply that in inflammatory
      diseases that result in persistent articular bone loss, strict control of
      inflammation may not be achieved and may be essential for the generation of an
      anabolic microenvironment that supports bone formation and repair.

PMID- 22139868
TI  - Meeting report of the 2011 Joint International Congress of the International
      Liver Transplantation Society, the European Liver and Intestine Transplant
      Association, and the Liver Intensive Care Group of Europe.
AB  - The International Liver Transplantation Society held its yearly meeting as a
      joint conference with the European Liver and Intestine Transplant Association and
      the Liver Intensive Care Group of Europe at the Valencia Congress Center
      (Valencia, Spain) from June 22 to 25, 2011. Nearly 1500 registrants attended the
      meeting, which opened with a premeeting conference entitled "Global Challenges
      and Controversies in Liver Transplantation." This was followed by numerous oral
      and poster abstract sessions and topic sessions focused on medical, surgical, and
      intensive care aspects of liver transplantation (LT). This report summarizes key
      symposia and oral abstracts delivered at the meeting and is conveniently divided
      into subsections relevant to LT. It is not meant to be a critical or
      comprehensive evaluation of all the meeting presentations and is merely intended
      to highlight presentations and associated published literature dealing with key
      topics.

PMID- 22139867
TI  - Prognostic value of ADAM17 in human gastric cancer.
AB  - A disintegrin and metalloproteinase-17 (ADAM17, also named as tumor necrosis
      factor-alpha-converting enzyme) is a member of the ADAM family. Of all ADAMs, the
      strongest evidence for a role in malignancy exists for ADAM17. Especially, it has
      been demonstrated that ADAM17 expression was significantly increased in human
      gastric cancer. The aim of this study was to investigate the association between
      ADAM17 expression and the clinicopathological features of patients with gastric
      cancer. The expression of ADAM17 was detected by real-time quantitative RT-PCR in
      gastric cancer and adjacent non-cancerous tissues. In addition, ADAM17 expression
      was analyzed by immunohistochemistry in 220 clinicopathologically characterized
      gastric cancer cases. The expression levels of ADAM17 mRNA and protein in gastric
      cancer tissues were both significantly higher than those in non-cancerous gastric
      mucosa. In addition, positive expression of ADAM17 correlated with the degree of
      tumor differentiation, depth of invasion, lymph node metastases, distant
      metastases, and TNM stage (all P<0.05). Furthermore, multivariate analysis
      suggested that lymph node metastases, distant metastases, TNM stage, and ADAM17
      expression were independent prognostic indicators for gastric cancer. Our data
      suggest for the first time that the increased expression of ADAM17 in gastric
      cancer is associated significantly with aggressive progression and poor
      prognosis. ADAM17 may be an important molecular marker for predicting the
      carcinogenesis, progression, and prognosis of gastric cancer.

PMID- 22139869
TI  - High tip angle approximation based on a modified Bloch-Riccati equation.
AB  - When designing a radio-frequency pulse to produce a desired dependence of
      magnetization on frequency or position, the small flip angle approximation is
      often used as a first step, and a Fourier relation between pulse and transverse
      magnetization is then invoked. However, common intuition often leads to linear
      scaling of the resulting pulse so as to produce a larger flip angle than the
      approximation warrants--with surprisingly good results. Starting from a modified
      version of the Bloch-Riccati equation, a differential equation in the flip angle
      itself, rather than in magnetization, is derived. As this equation has a
      substantial linear component that is an instance of Fourier's equation, the
      intuitive approach is seen to be justified. Examples of the accuracy of this
      higher tip angle approximation are given for both constant- and variable-phase
      pulses.

PMID- 22139872
TI  - Highly efficient Cu(OAc)2-catalyzed dimerization of monofunctionalized
      hydrofullerenes leading to single-bonded [60]fullerene dimers.

PMID- 22139870
TI  - Green fluorescent protein changes the conductance of connexin 43 (Cx43)
      hemichannels reconstituted in planar lipid bilayers.
AB  - In mammalian tissues, connexin 43 (Cx43) is the most prominent member of the
      connexin family. In a single lipid bilayer, six connexin subunits assemble into a
      hemichannel (connexon). Direct communication of apposing cells is realized by two
      adjacent hemichannels, which can form gap junction channels. Here, we established
      an expression system in Pichia pastoris to recombinantly produce and purify Cx43
      as well as Cx43 fused to green fluorescent protein (GFP). Proteins were isolated
      from crude cell membrane fractions via affinity chromatography. Cx43 and Cx43-GFP
      hemichannels were reconstituted in giant unilamellar vesicles as proven by
      fluorescence microscopy, and their electrophysiological behavior was analyzed on
      the single channel level by planar patch clamping. Cx43 and Cx43-GFP both showed
      an ohmic behavior and a voltage-dependent open probability. Cx43 hemichannels
      exhibited one major mean conductance of 224 +/- 26 picosiemens (pS). In addition,
      a subconductance state at 124 +/- 5 pS was identified. In contrast, the analysis
      of Cx43-GFP single channels revealed 10 distinct conductance states in the range
      of 15 to 250 pS, with a larger open probability at 0 mV as compared with Cx43,
      which suggests that intermolecular interactions between the GFP molecules alter
      the electrophysiology of the protein.

PMID- 22139871
TI  - Myristic acid increases dihydroceramide Delta4-desaturase 1 (DES1) activity in
      cultured rat hepatocytes.
AB  - Dihydroceramide Delta4-desaturase 1 (DES1) catalyzes the last step of the de novo
      ceramide biosynthesis, which consists of the introduction of a trans Delta4
      double bond in the carbon chain of the dihydroceramide. It was previously
      observed that myristic acid binds DES1 through N-myristoylation. This N-terminal
      modification significantly increased the activity of the recombinant DES1 in COS
      7 cells and targeted part of the enzyme initially present in the endoplasmic
      reticulum to the mitochondrial outer membrane, leading to an increase in ceramide
      levels. Since these results were obtained in a recombinant COS-7 cell model with
      high expression of rat DES1, the purpose of the present study was to investigate
      if the native DES1 enzyme was really upregulated by its N-myristoylation in
      cultured rat hepatocytes. We first showed that DES1 was the main dihydroceramide
      desaturase isoform expressed in rat hepatocytes. In this model, the wild-type
      myristoylable recombinant form of rat DES1 was found in both the endoplasmic
      reticulum and the mitochondria whereas the mutated non-myristoylable recombinant
      form (N-terminal glycine replaced by an alanine) was almost exclusively localized
      in the endoplasmic reticulum, which evidenced the importance of the
      myristoylation. Then, we showed that compared to other fatty acids, myristic acid
      was the only one to increase native DES1 activity, in both total cell lysates and
      mitochondrial fractions. The myristic acid-associated increase in DES1 activity
      was not linked to elevated mRNA or protein expression but more likely to its N
      terminal myristoylation. Finally, the myristic acid-associated increase in DES1
      activity slightly enhanced the number of apoptotic cells.

PMID- 22139874
TI  - [Selected summaries].

PMID- 22139873
TI  - Intermittent observation of time-dependent explanatory variables: a multistate
      modelling approach.
AB  - Motivated by investigations of factors related to various patient-reported
      outcome measures in psoriatic arthritis patients, after controlling for the
      effect of disease activity on these outcomes, we outline an approach for dealing
      with a rapidly fluctuating explanatory variable in a multistate model. On the
      basis of a representation of this variable as an ordinal classification, we
      suggest the use of an expanded multistate model. We examine the bias in
      estimating effects associated with other variables via simulation for different
      modelling choices. We present an analysis of a motivating data set on physical
      functional disability in psoriatic arthritis patients.

PMID- 22139875
TI  - NOD2 sequencing in Iranian children with Crohn's disease.
AB  - Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal
      tract. Although the exact etiology of disease is still unknown, mutations in the
      CARD15/NOD2 gene have been reported in association with CD in several studies.
      This study was performed to determine whether the CARD15/NOD2 gene confers
      susceptibility to Iranian pediatric patients with CD. All 12 coding exons of the
      CARD15/NOD2 gene were sequenced in 16 enrolled pediatric onset CD patients.
      Sequencing of the CARD15/NOD2 gene showed no mutation. However, two patients
      harbored polymorphisms within this gene. A heterozygous single nucleotide
      polymorphism rs3135500 C > Y in the exon 12.3 was detected in a 10-year-old girl
      with mild severity of CD and history of rectovaginal and perianal fistula, and
      multiple skin tags. The other 5-year-old boy with moderate to severe CD and a
      history of perianal fissures and oral candidiasis harbored heterozygous single
      nucleotide polymorphisms in exons 4.1 and 12.1. The results of the present study
      show that the CARD15/NOD2 mutations in Iranian patients with pediatric onset CD
      are not responsible for the pathogenesis of disease.

PMID- 22139876
TI  - Probe-based confocal laser endomicroscopy in double balloon enteroscopy.
AB  - BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) allows in-vivo
      assessment of the gastrointestinal mucosal architecture during ongoing endoscopy.
      We investigated the feasibility and safety of pCLE during double balloon
      enteroscopy (DBE). METHODS: DBE was performed using the Fujinon EN-450P5. pCLE
      (Cellvizio-GI(r), Mauna Kea Technologies) was performed after intravenous
      injection of 5-10  mL fluorescein 1 % using a 1.8-mm probe (GastroFlex/ColoFlex Z
      probe) at the deepest point of DBE insertion and in case of any pathological
      lesion. Primary outcome measure was technical success, defined as (i) successful
      advancement of the probe at the deepest DBE insertion and (ii) successful pCLE
      imaging of the intestinal mucosa. Secondary outcome was safety of the pCLE
      procedure. RESULTS: 27 DBE procedures (14 antegrade) were performed in 16
      patients. The mean depth of small bowel insertion was 255  cm for antegrade and
      130  cm for retrograde DBE. Technical success of pCLE was achieved in 96.3 %
      (antegrade 92.8 %, retrograde 100 %). One technical failure occurred (incomplete
      probe advancement). There were no adverse events related to the pCLE procedure.
      pCLE imaging of the small bowel mucosal architecture was possible in all cases.
      Pathological conditions within the small bowel such as loss of villi, crypt
      hyperplasia, advanced neoplasia, or increased blood flow due to inflammation
      tissue could be successful visualized. CONCLUSION: This study is the first to
      demonstrate successful and safe application of pCLE in the deep small bowel
      during double balloon enteroscopy. Further studies are needed to determine the
      clinical benefit of pCLE in the management of patients with small bowel diseases.

PMID- 22139877
TI  - [The clinical spectrum of urea cycle defects in adult patients].
AB  - Urea cycle defects belong to the most common metabolic disorders with a
      cumulative incidence of 1:8000. A common trait of urea cycle defects is a
      disturbed detoxification of ammonia leading to hyperammonemia in the event of a
      high nitrogen load. Most patients develop symptoms in the neonatal period or in
      infancy, e. g. vomiting, seizures and disturbed consciousness. Depending on the
      affected enzyme and its residual activity, patients differ in the age at first
      presentation, the character and severity of symptoms and in the susceptibility to
      metabolic derangement. The presence of hyperammonemia and an altered plasma amino
      acid profile give the essential diagnostic clues. Since modern therapeutic
      measures have prolonged the life expectancy of these patients and provided the
      possibility of a first presentation in adulthood, patients with urea cycle
      defects have become an increasing challenge in internal medicine. The reported
      case series illustrates the heterogeneous clinical course of these disorders from
      childhood to adulthood.

PMID- 22139878
TI  - Review of the literature and description of a case of sclerosing encapsulating
      peritonitis requiring home parenteral nutrition.
AB  - We present a case of a 48 year old HIV patient, who had recurrent episodes of
      ascites since 2007. His history includes ischaemic heart disease, for which he
      was treated with atenolol from 2005 to 2007, and Type 2 diabetes; he was later
      started on propranolol 40  mg twice a day from 2007 for Didanosine-induced portal
      hypertension. Because of negative cultures and neutrophil count < 250 cells/MUL,
      spontaneous bacterial peritonitis was excluded. However, some low grade
      peritoneal irritation cannot be ruled out because his CRP varied from 24 to 258,
      during 2007 - 2009, without any other obvious inflammatory cause. He was finally
      diagnosed in July 2009 with sclerosing encapsulating peritonitis (SEP) based on
      clinical features of intestinal obstruction, histology and imaging, including
      computed tomography and magnetic resonance imaging. Propranolol was stopped in
      November 2009.  Because of the patient's severe intestinal obstruction, he was
      started on parenteral nutrition 2  L/day. Since then, his CRP has returned to
      normal levels and there is a great improvement of his clinical features. This
      case demonstrates beta-blockers as a potential cause of SEP, while the presence
      of some low-grade peritoneal inflammation leading to SEP is also very likely.

PMID- 22139879
TI  - [Lack of data relevant for German transplantation medicine].
AB  - Collection of data in transplantation medicine is required to define ethical
      standards, to assess indications and contra-indications and to determine rules
      for organ allocation. Similarly, assessment of quality of the transplantation
      process and practice of transplantation centres requires relevant data in
      transplantation medicine. Apart from data in quality reports, Eurotransplant and
      organ procurement, any form of data collection is lacking in Germany. In this
      article the problems caused by this shortcoming are described.

PMID- 22139880
TI  - Cholestasis and the role of basolateral efflux pumps.
AB  - ATP-dependent transport of biliary constituents, such as bile acids, reduced
      glutathione, and bilirubin glucuronosides across the hepatocyte canalicular
      membrane into bile represents the decisive driving force for the formation of
      biliary fluid. Functional characterization, cloning, and localization of
      hepatocellular transporter proteins has provided a molecular understanding of the
      mechanisms underlying bile flow and intrahepatic cholestasis. Genetic variants in
      humans and genetic knockout in rodents, or transporter inhibition have indicated
      that both the conjugate export pump MRP2 (multidrug resistance protein 2; ABCC2)
      and the bile salt export pump BSEP (ABCB11) are major contributors to bile acid
      independent and bile acid-dependent bile flow, respectively. In humans, genetic
      variants of BSEP, leading to an impaired transport activity or localization of
      the protein in the canalicular membrane, are associated with severe intrahepatic
      cholestasis. Efflux pumps of the basolateral hepatocyte membrane, particularly
      MRP3 (multidrug resistance protein 3; ABCC3) and MRP4 (multidrug resistance
      protein 4; ABCC4) pump substances from hepatocytes into sinusoidal blood. These
      efflux pumps have been recognized in recent years to play an important
      compensatory role in cholestasis and to contribute to the balance between uptake
      and efflux of substances during the vectorial transport from sinusoidal blood
      into bile. This sinusoidal efflux not only enables subsequent renal elimination,
      but also re-uptake of substances into neighboring and more centrally located
      hepatocytes in the sinusoid.

PMID- 22139881
TI  - [Microsatellite instability in colon cancer: important to decide over adjuvant
      treatment?].

PMID- 22139883
TI  - Clinical images: detection of gouty arthritis in the atlantoaxial joint using
      dual-energy computed tomography.

PMID- 22139882
TI  - Clinical predictors of cognitive function in adults treated with hematopoietic
      cell transplantation.
AB  - BACKGROUND: Studies suggest that patients with cancer who undergo hematopoietic
      cell transplantation (HCT) are at risk for cognitive deficits. To date, little
      research has investigated the cumulative effects of clinical risk factors on
      cognitive function in patients who undergo HCT. METHODS: Patients (N = 278) who
      were scheduled to undergo HCT for hematologic disease completed
      neuropsychological assessments before HCT and at 6 months and 12 months after
      HCT. A time-varying cumulative clinical risk variable was examined as a predictor
      of total neuropsychological performance (TNP). Cumulative clinical risk was
      calculated from pre-HCT neuropsychological risk factors (eg, history of cranial
      irradiation, intrathecal chemotherapy), HCT-related risk factors (eg, allogeneic
      transplantation, unrelated donor), and post-HCT complications (eg, severity of
      mucositis and enteritis, graft-versus-host disease). RESULTS: Patients with
      greater cumulative clinical risk displayed worse TNP at baseline and at 6 months
      after HCT and less neuropsychological recovery over time than patients who had
      less risk (Ps < .05). Greater cumulative clinical risk predicted worse
      performance on tasks assessing executive function at baseline and 6 months after
      HCT and assessing memory at 6 months and 12 months after HCT (Ps < .05). Among
      risk variables, length of hospital stay was the only significant predictor of
      neuropsychological function (P < .05). CONCLUSIONS: Findings from this study
      indicated that clinical risk factors may have a cumulative effect on cognitive
      function in patients who undergo HCT. Patients who have a complicated clinical
      course should be referred for evaluation and management of cognitive deficits.

PMID- 22139884
TI  - LINE-1 retrotransposon copies are amplified during murine early embryo
      development.
AB  - Two large families of retrotransposons, that is, LINE-1 (Long Interspersed
      Nuclear Elements-1) and endogenous retroviruses, encode reverse transcriptase
      (RT) proteins in vertebrates. We previously showed that mouse preimplantation
      embryos are endowed with an endogenous, functional RT activity. Inhibiting that
      activity by microinjecting antisense oligonucleotides against a highly active
      LINE-1 family member in mouse oocytes blocked developmental progression between
      the two- and four-blastomere stages, indicating that LINE-1-encoded RT activity
      is strictly required at this critical transition in early development. Here we
      show that incubation of mouse zygotes with 5'-bromodeoxyuridine (BrdU) yields
      massive incorporation of this nucleoside analogue in newly synthesized DNA;
      surprisingly, a significant incorporation still occurs in both zygotic pronuclei
      in the presence of aphidicolin, a specific inhibitor of DNA replication. This
      aphidicolin-resistant BrdU incorporation is quantitatively abolished when embryos
      are simultaneously exposed to abacavir, a nucleoside RT inhibitor, indicating its
      retrotranscription-dependent nature. Moreover, quantitative PCR analysis revealed
      a burst of new synthesis of LINE-1 copies at the zygote- and two-cell embryo
      stages. These findings support the conclusion that RT-dependent amplification of
      LINE-1 retrotransposons is a distinctive feature of early embryonic genomes. Its
      physiological involvement in preimplantation murine development is discussed.

PMID- 22139885
TI  - The peptide derived from erbB2 auto-inhibitor herstatin shared in the same
      epitope and function with functional antibody 2C4.
AB  - Previous studies have shown that different epitopes of HER2 exhibit distinct
      functions and that the epitope bound by the antibody 2C4 plays a role in
      formation of hetereodimers between HER2 and other receptors of the HER family. In
      this study, we used computer modeling to determine that the epitope of HER2 which
      the C-terminal 79 amino acids of herstatin (named HSTC79) binds is similar to
      that bound by 2C4. Based on these theoretical results, recombinant HSTC79 fused
      with GST was expressed in Escherichia coli and purified by affinity
      chromatography. Experimental analysis showed that HSTC79 did specifically bind to
      HER2 and that the epitope of HER2 identified by HSTC79 was near that identified
      by 2C4. Furthermore, HSTC79 inhibited the growth of HER2-overexpressing cells.
      These results highlight the fact that the binding site architecture and certain
      key residues of HER2 may be very helpful for understanding the protein's
      biological role and providing insights for designing novel inhibitors of HER2.

PMID- 22139886
TI  - Randomized ablation strategies for the treatment of persistent atrial
      fibrillation: RASTA study.
AB  - BACKGROUND: The single-procedure efficacy of pulmonary vein isolation (PVI) is
      less than optimal in patients with persistent atrial fibrillation (AF).
      Adjunctive techniques have been developed to enhance single-procedure efficacy in
      these patients. We conducted a study to compare 3 ablation strategies in patients
      with persistent AF. METHODS AND RESULTS: Subjects were randomized as follows: arm
      1, PVI + ablation of non-PV triggers identified using a stimulation protocol
      (standard approach); arm 2, standard approach + empirical ablation at common non
      PV AF trigger sites (mitral annulus, fossa ovalis, eustachian ridge, crista
      terminalis, and superior vena cava); or arm 3, standard approach + ablation of
      left atrial complex fractionated electrogram sites. Patients were seen at 6
      weeks, 6 months, and 1 year; transtelephonic monitoring was performed at each
      visit. Antiarrhythmic drugs were discontinued at 3 to 6 months. The primary study
      end point was freedom from atrial arrhythmias off antiarrhythmic drugs at 1 year
      after a single-ablation procedure. A total of 156 patients (aged 59+/-9 years;
      136 males; AF duration, 47+/-50 months) participated (arm 1, 55 patients; arm 2,
      50 patients; arm 3, 51 patients). Procedural outcomes (procedure, fluoroscopy,
      and PVI times) were comparable between the 3 arms. More lesions were required to
      target non-PV trigger sites than a complex fractionated electrogram (33+/-9
      versus 22+/-9; P<0.001). The primary end point was achieved in 71 patients and
      was worse in arm 3 (29%) compared with arm 1 (49%; P=0.04) and arm 2 (58%;
      P=0.004). CONCLUSIONS: These data suggest that additional substrate modification
      beyond PVI does not improve single-procedure efficacy in patients with persistent
      AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00379301.

PMID- 22139887
TI  - Imaging study of ventricular scar in arrhythmogenic right ventricular
      cardiomyopathy: comparison of 3D standard electroanatomical voltage mapping and
      contrast-enhanced cardiac magnetic resonance.
AB  - BACKGROUND: The hallmark lesion of arrhythmogenic right ventricular
      cardiomyopathy (ARVC) is fibrofatty scar replacement. We compared endocardial
      voltage mapping (EVM) and contrast-enhanced cardiac magnetic resonance (CE-CMR)
      for imaging scar lesions in ARVC patients. METHODS AND RESULTS: We studied 23
      consecutive ARVC patients (16 males; mean age, 38+/-12 years) who underwent RV
      EVM and CE-CMR and 37 control subjects. In 21 (91%) of 23 ARVC patients, RV EVM
      was abnormal, with a total of 45 electroanatomical scars (EAS): 17 (38%) in the
      inferobasal region, 12 (26.6%) in the anterolateral region, 8 (17.7%) in the RV
      outflow tract (RVOT), and 8 (17.7%) in the apex. RV delayed contrast enhancement
      (DCE) was found in 9 (39%) of 23 patients, with a total of 23 RV DCE scars: 4
      (17.4%) in the inferobasal region, 9 (39.1%) in the anterolateral region, 4
      (17.4%) in the RVOT, and 6 (26.1%) in the apex. There was a mismatch in 24 RV
      scars, with 22 EAS not confirmed by DCE and 2 DCE scars (both in the RVOT)
      undetected by EVM. In 9 (75%) of 12 patients with abnormal RV EVM/normal RV DCE,
      >=1 DCEs were identified in the left ventricle (LV). Overall, ventricular DCE was
      detected in 78% of patients. No control subjects showed either EAS or DCE.
      CONCLUSIONS: EVM and CE-CMR allow identification of RV scar lesions in most ARVC
      patients. CE-CMR is less sensitive than EVM in identifying RV scar lesions. The
      high prevalence of LV DCE confirms the frequent biventricular involvement and
      indicates the diagnostic relevance of LV scar detection by CE-CMR.

PMID- 22139888
TI  - Retrospective review of the incidence of cytomegalovirus infection and disease
      after liver transplantation in pediatric patients: comparison of prophylactic
      oral ganciclovir and oral valganciclovir.
AB  - Cytomegalovirus (CMV) is the most common viral infection after solid organ
      transplantation (SOT). Safe and effective prophylactic regimens that decrease its
      incidence after SOT are essential for long-term graft survival. Although
      valganciclovir is not Food and Drug Administration-approved for CMV prophylaxis
      in liver transplant recipients, postmarketing studies have shown valganciclovir
      to be as effective as ganciclovir in high-risk adult patients undergoing SOT.
      Currently, data are lacking for pediatric liver transplantation. The purpose of
      this study was to compare the efficacy and safety of valganciclovir and
      ganciclovir for CMV infection prophylaxis in pediatric liver transplant
      recipients. This was a retrospective study of 56 pediatric liver transplant
      recipients who were prescribed either oral ganciclovir (n = 37) or valganciclovir
      (n = 19). Patients were followed until 200 days after transplantation or death.
      The primary outcome measure compared the rates of early-onset CMV infection and
      CMV disease in the 2 medication groups. Secondary outcome measures identified
      patient-specific factors that contributed to CMV acquisition and the incidence of
      late-onset CMV infection or disease. The rates of adverse drug effects and
      discontinuation were also evaluated. Early-onset CMV disease was documented in 0%
      of valganciclovir patients and in 5.4% of ganciclovir patients (P = 0.54). There
      were no statistically significant differences in the secondary outcomes. An
      increased incidence of late-onset CMV disease was seen in the valganciclovir
      group versus the ganciclovir group (22.2% versus 8.1%, P = 0.23). No differences
      in adverse events were reported. In conclusion, no statistically significant
      differences were found in the incidence of CMV infection or disease between
      patients receiving oral valganciclovir and patients receiving oral ganciclovir.

PMID- 22139889
TI  - Shared velocity encoding: a method to improve the temporal resolution of phase
      contrast velocity measurements.
AB  - Phase-contrast magnetic resonance imaging (PC-MRI) is used routinely to measure
      fluid and tissue velocity with a variety of clinical applications. Phase-contrast
      magnetic resonance imaging methods require acquisition of additional data to
      enable phase difference reconstruction, making real-time imaging problematic.
      Shared Velocity Encoding (SVE), a method devised to improve the effective
      temporal resolution of phase-contrast magnetic resonance imaging, was implemented
      in a real-time pulse sequence with segmented echo planar readout. The effect of
      SVE on peak velocity measurement was investigated in computer simulation, and
      peak velocities and total flow were measured in a flow phantom and in volunteers
      and compared with a conventional ECG-triggered, segmented k-space phase-contrast
      sequence as a reference standard. Computer simulation showed a 36% reduction in
      peak velocity error from 8.8 to 5.6% with SVE. A similar reduction of 40% in peak
      velocity error was shown in a pulsatile flow phantom. In the phantom and
      volunteers, volume flow did not differ significantly when measured with or
      without SVE. Peak velocity measurements made in the volunteers using SVE showed a
      higher concordance correlation (0.96) with the reference standard than non-SVE
      (0.87). The improvement in effective temporal resolution with SVE reconstruction
      has a positive impact on the precision and accuracy of real-time phase-contrast
      magnetic resonance imaging peak velocity measurements.

PMID- 22139890
TI  - Detection of a prognostic indicator in early-stage cancer using functionalized
      graphene-based peptide sensors.

PMID- 22139891
TI  - Improper analysis of trials randomised using stratified blocks or minimisation.
AB  - Many clinical trials restrict randomisation using stratified blocks or
      minimisation to balance prognostic factors across treatment groups. It is widely
      acknowledged in the statistical literature that the subsequent analysis should
      reflect the design of the study, and any stratification or minimisation variables
      should be adjusted for in the analysis. However, a review of recent general
      medical literature showed only 14 of 41 eligible studies reported adjusting their
      primary analysis for stratification or minimisation variables. We show that
      balancing treatment groups using stratification leads to correlation between the
      treatment groups. If this correlation is ignored and an unadjusted analysis is
      performed, standard errors for the treatment effect will be biased upwards,
      resulting in 95% confidence intervals that are too wide, type I error rates that
      are too low and a reduction in power. Conversely, an adjusted analysis will give
      valid inference. We explore the extent of this issue using simulation for
      continuous, binary and time-to-event outcomes where treatment is allocated using
      stratified block randomisation or minimisation.

PMID- 22139892
TI  - Determination of diabetic retinopathy prevalence and associated risk factors in
      Chinese diabetic and pre-diabetic subjects: Shanghai diabetic complications
      study.
AB  - BACKGROUND: The prevalence of diabetic retinopathy is not well studied in the
      Chinese pre-diabetic population, also known as impaired glucose regulation.
      Hence, we investigated the prevalence of and risk factors associated with
      retinopathy in diabetic and pre-diabetic subjects from Chinese communities.
      METHODS: A total of 3736 Chinese subjects were recruited from urban communities
      in Shanghai. The participants were classified as normal glucose tolerance,
      impaired glucose regulation (IGR) and diabetes based on the 75 g oral glucose
      tolerance test. The levels of diabetic retinopathy (DR) were assessed with non
      mydriatic retinal photographs according to the Diabetic Retinopathy Disease
      Severity Scale. RESULTS: The prevalence of diabetic retinopathy in patients with
      diabetes and impaired glucose regulation subjects was 9.4% and 2.5%,
      respectively. In subjects with IGR, hypertension (odds ratio: 3.54, p = 0.028),
      including elevated systolic and diastolic blood pressure and obesity (odds ratio:
      3.53, p = 0.028) were significantly associated with diabetic retinopathy after
      age and sex adjustments. The factors associated with retinopathy in diabetes
      included diabetes duration, blood glucose levels, glycated hemoglobin levels, and
      the presence of albuminuria. Diabetic retinopathy was significantly associated
      with fasting plasma glucose in known diabetes, whereas in newly-diagnosed
      subjects, diabetic neuropathy was closely correlated to postprandial plasma
      glucose. CONCLUSIONS: Hyperglycemia was a strong risk factor for diabetic
      retinopathy. In pre-diabetic subjects, diabetic retinopathy was also associated
      with hypertension and obesity.

PMID- 22139894
TI  - Improved survival for BRCA2-associated serous ovarian cancer compared with both
      BRCA-negative and BRCA1-associated serous ovarian cancer.
AB  - BACKGROUND: Multiple observational studies have suggested that breast cancer gene
      (BRCA)-associated ovarian cancers have improved survival compared with BRCA
      negative ovarian cancers. However, most of those studies combined BRCA1 and BRCA2
      patients or evaluated only BRCA1 patients. The objective of the current study was
      to examine whether BRCA1-associated and BRCA2-associated ovarian cancers were
      associated with different outcomes. METHODS: This was a single-institution,
      retrospective analysis of patients who had a new diagnosis of histologically
      confirmed stage III or IV serous ovarian, fallopian tube, or primary peritoneal
      cancer between January 1, 1996 and February 1, 2011 and who underwent BRCA
      mutation testing on 1 of 2 institutional review board-approved follow-up studies.
      Patients who had been tested for BRCA mutations beyond 24 months of diagnosis
      were excluded from analysis to minimize selection bias from including patients
      who were referred for genetic testing because of long survival. RESULTS: Data
      from 190 patients (143 BRCA-negative patients, 30 BRCA1-positive patients, and 17
      BRCA2-positive patients) were analyzed. During the study period, 73 deaths were
      observed (60 BRCA-negative patients, 10 BRCA1-positive patients, 3 BRCA2-positive
      patients). The median follow-up for the remaining 117 survivors was 2.5 years. At
      3 years, 69.4%, 90.7%, and 100% of BRCA-negative patients, BRCA1-positive
      patients, and BRCA2-positive patients were alive, respectively. On univariate
      analysis, age, BRCA2 mutations, debulking status, and type of first-line therapy
      (intravenous or intraperitoneal) were significant predictors of overall survival.
      On multivariate analysis, BRCA2 mutations (hazard ratio, 0.20; 95% confidence
      interval, 0.06-0.65; P = .007), but not BRCA1 mutations (hazard ratio, 0.70; 95%
      confidence interval, 0.36-1.38; P = .31), predicted for improved overall survival
      compared with BRCA-negative patients. When carriers of BRCA2 mutations were
      directly compared with carriers of BRCA1 mutations, BRCA2 mutations appeared to
      confer improved overall survival (hazard ratio, 0.29; 95% confidence interval,
      0.08-1.05; P = .060), although this finding did not reach significance.
      CONCLUSIONS: The current data suggests that BRCA2 mutations confer an overall
      survival advantage compared with either being BRCA-negative or having a BRCA1
      mutation in high-grade serous ovarian cancer. This finding may have important
      implications for clinical trial design.

PMID- 22139895
TI  - Systemic autoimmunity caused by fas deficiency in macrophages: a new perspective
      on the first identified autoimmunity gene.

PMID- 22139893
TI  - Daily intake of cod or salmon for 2 weeks decreases the 18:1n-9/18:0 ratio and
      serum triacylglycerols in healthy subjects.
AB  - Intake of fish and omega-3 (n-3) fatty acids is associated with a reduced
      concentration of plasma triacylglycerols (TAG) but the mechanisms are not fully
      clarified. Stearoyl-CoA desaturase-1 (SCD1) activity, governing TAG synthesis, is
      affected by n-3 fatty acids. Peripheral blood mononuclear cells (PBMC) display
      expression of genes involved in lipid metabolism. The aim of the present study
      was to estimate whether intake of lean and fatty fish would influence n-3 fatty
      acids composition in plasma phospholipids (PL), serum TAG, 18:1n-9/18:0 ratio in
      plasma PL, as well as PBMC gene expression of SCD1 and fatty acid synthase (FAS).
      Healthy males and females (n = 30), aged 20-40, consumed either 150 g of cod,
      salmon, or potato (control) daily for 15 days. During intervention
      docosahexaenoic acid (DHA, 22:6n-3) increased in the cod group (P < 0.05), while
      TAG concentration decreased (P < 0.05). In the salmon group both eicosapentaenoic
      acid (EPA, 20:5n-3) and DHA increased (P < 0.05) whereas TAG concentration and
      the 18:1n-9/18:0 ratio decreased (P < 0.05). Reduction of the 18:1n-9/18:0 ratio
      was associated with a corresponding lowering of TAG (P < 0.05) and an increase in
      EPA and DHA (P < 0.05). The mRNA levels of SCD1 and FAS in PBMC were not
      significantly altered after intake of cod or salmon when compared with the
      control group. In conclusion, both lean and fatty fish may lower TAG, possibly by
      reducing the 18:1n-9/18:0 ratio related to allosteric inhibition of SCD1
      activity, rather than by influencing the synthesis of enzyme protein.

PMID- 22139896
TI  - Carbon nanocages as supercapacitor electrode materials.
AB  - Supercapacitor electrode materials: Carbon nanocages are conveniently produced by
      an in situ MgO template method and demonstrate high specific capacitance over a
      wide range of charging-discharging rates with high stability, superior to the
      most carbonaceous supercapacitor electrode materials to date. The large specific
      surface area, good mesoporosity, and regular structure are responsible for the
      excellent performance.

PMID- 22139897
TI  - Exercise capacity and muscle strength in patients with cirrhosis.
AB  - Exercise capacity and muscle strength are predictors of outcome in a number of
      clinical populations. Advanced liver disease is a catabolic state, and patients
      often have muscle wasting. However, the relationships between exercise capacity,
      strength, and outcomes for patients undergoing liver transplantation are poorly
      understood. Thirteen studies have examined the association between these
      parameters in patients with cirrhosis, and they have found a significant
      reduction in the exercise capacity and muscle strength of patients with cirrhosis
      versus healthy controls. These impairments appear to be independent of the
      etiology of cirrhosis, but the data are equivocal with respect to their
      association with disease severity. Two studies reported a significant and
      independent association between pretransplant exercise capacity and
      posttransplant survival. Another 2 studies found that exercise training was well
      tolerated in patients with cirrhosis and resulted in improvements in exercise
      capacity (both studies) and muscle mass (1 study). These data are provocative and
      suggest that measuring and improving the exercise capacity and muscle strength of
      patients with cirrhosis who are awaiting liver transplantation could potentially
      improve outcomes.

PMID- 22139898
TI  - Expression of estrogen receptor alpha switches off secretory activity in the
      epididymal channel of the lizard Podarcis sicula.
AB  - The epididymis in the male reproductive tract allows the survival, viability, and
      storage of spermatozoa from the testis. In the lizard Podarcis sicula, the
      epididymis can be regionalized to an initial segment called the caput that
      comprises the efferent ductules, followed by the middle and terminal segments,
      respectively termed the corpus and cauda. By means of in situ hybridization and
      immunocytochemistry, we analyzed the expression of the estrogen receptors of the
      alpha and beta type (ERalpha and ERbeta) in Podarcis to test the responsiveness
      of the epididymal regions to estrogen in the annual reproductive cycle of this
      seasonal breeder. The results show that the efferent ductules and the cauda
      always express both ERalpha and ERbeta throughout the year. In the corpus, the
      expression of ERalpha takes place only at the end of the mating period and
      continues in the non-reproductive season whereas ERbeta is expressed in all
      phases of the cycle. During the mating season, the cells of the corpus are
      engaged in massive secretory activity and do not express ERalpha. Experimental
      administration of E(2) during this season does not change the expression of
      ERbeta, nor does it affect the efferent ductules and cauda; instead, it inhibits
      the secretory activity in the corpus and induces the expression of ERalpha. Taken
      together, our findings suggest that in the epididymis of Podarcis, the expression
      of ERalpha may act as a switch for the secretory activity of the epididymal
      corpus.

PMID- 22139899
TI  - Medical care of adolescents and women with Rett syndrome: an Italian study.
AB  - Rett syndrome (RTT) is a rare neurodevelopmental disorder, linked to MECP2 gene
      mutations in the majority of cases, which results in severe disability and is
      associated with several comorbidities. The clinical condition of RTT patients
      tends to stabilize over time, and prolonged survival has recently been
      demonstrated. However, limited information is available on the long-term course
      of older patients with RTT, especially among those in Southern Europe. The aim of
      our study is to evaluate the main clinical features and state of health of adult
      Italian patients with RTT and to present their evolution over time, identifying
      major clinical issues present at different ages. A total of 130 families of
      patients with RTT aged >=14 years were asked to complete a questionnaire, 84 of
      which were returned (65%). Among the clinical characteristics of RTT,
      stereotypies and poor hand function and feeding ability remained stable over
      time, while nonverbal communication tended to improve. With regard to the main
      pathologies, sleep, behavioral, and autonomic disorders persisted into adulthood,
      while epilepsy improved and musculoskeletal problems worsened. In our sample,
      older patients with R294X and R133C mutations and with C-terminal deletions
      showed lower levels of clinical severity. The development of guidelines for the
      clinical management of patients with RTT will assist health care providers in
      dealing with the complex RTT phenotype. More extensive data about the long-term
      course of the condition could help in the design of programs for secondary
      prevention of disabilities for younger females affected by the syndrome.

PMID- 22139900
TI  - Preserving the accuracy and resolution of the sodium bioscale from quantitative
      sodium MRI during intrasubject alignment across longitudinal studies.
AB  - Emerging applications of sodium bioscales derived from quantitative sodium
      magnetic resonance imaging assess temporal changes in regional sodium
      concentration over intervals that vary from hours (monitoring tissue viability in
      stroke) to weeks (monitoring brain tumor treatment during radiation therapy) or
      even years (monitoring progression of neurodegenerative disease). Accurate
      interpretation of such quantitative data requires precise registration between
      magnetic resonance imaging sessions to avoid session-to-session changes in
      partial volume effects between normal tissue (~38 mM sodium concentration),
      lesions (variable sodium concentration), and cerebrospinal fluid (~144 mM sodium
      concentration). The existing Automated Image Registration algorithm is shown to
      be suitable for rapid, accurate, and precise determination of the transform that
      aligns sodium magnetic resonance images. Implementation of this transform during
      image reconstruction from the k-space data is shown to produce smaller errors
      than conventional image-domain interpolation. Experimental results at 9.4 T and
      3.0 T demonstrating this registration approach to sodium data illustrate
      preservation of quantification accuracy during alignment of sodium magnetic
      resonance images acquired from the same subject during different imaging
      sessions.

PMID- 22139902
TI  - Peripheral blood and bone marrow findings in B-cell lymphoma, unclassifiable with
      features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

PMID- 22139901
TI  - Global profiling of reactive oxygen and nitrogen species in biological systems:
      high-throughput real-time analyses.
AB  - Herein we describe a high-throughput fluorescence and HPLC-based methodology for
      global profiling of reactive oxygen and nitrogen species (ROS/RNS) in biological
      systems. The combined use of HPLC and fluorescence detection is key to successful
      implementation and validation of this methodology. Included here are methods to
      specifically detect and quantitate the products formed from interaction between
      the ROS/RNS species and the fluorogenic probes, as follows: superoxide using
      hydroethidine, peroxynitrite using boronate-based probes, nitric oxide-derived
      nitrosating species with 4,5-diaminofluorescein, and hydrogen peroxide and other
      oxidants using 10-acetyl-3,7-dihydroxyphenoxazine (Amplex(r) Red) with and
      without horseradish peroxidase, respectively. In this study, we demonstrate real
      time monitoring of ROS/RNS in activated macrophages using high-throughput
      fluorescence and HPLC methods. This global profiling approach, simultaneous
      detection of multiple ROS/RNS products of fluorescent probes, developed in this
      study will be useful in unraveling the complex role of ROS/RNS in redox
      regulation, cell signaling, and cellular oxidative processes and in high
      throughput screening of anti-inflammatory antioxidants.

PMID- 22139903
TI  - Management of multiple drug allergies in children.
AB  - Children with multiple drug allergies are likely to require treatment with one or
      more of the drugs to which they may have had a reaction, when there is no
      alternate effective drug available. Detailed review of their history and/or use
      of appropriate diagnostic studies will help determine the potential safety of
      readministering the desired drug as well as the method for its readministration,
      most likely in the form of a drug challenge or desensitization. A practical
      approach to the diagnosis and treatment of children with multiple drug allergies
      is described in this review.

PMID- 22139905
TI  - Health literacy and medication understanding among hospitalized adults.

PMID- 22139906
TI  - Predictive impact of MGMT promoter methylation in glioblastoma of the elderly.
AB  - O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation identifies a
      subpopulation of glioblastoma patients with more favorable prognosis and predicts
      a benefit from alkylating agent chemotherapy (CT). Little is known about its
      prevalence and clinical significance in older glioblastoma patients. We studied
      233 glioblastoma patients aged 70 years or more (144 males, 89 females, median
      age: 74 years, range: 70.0-86.6 years), who were prospectively enrolled in the
      German Glioma Network, for MGMT promoter methylation by methylation-specific PCR
      (MSP) in all patients and DNA pyrosequencing in 166 patients. MGMT data were
      correlated with patient outcome. Median progression-free survival (PFS) was 4.8
      months (95% CI: 4.3-5.3) and median overall survival (OS) was 7.7 months (95% CI:
      6.3-9.0). MGMT promoter methylation was detected by MSP in 134 patients (57.5%).
      For the whole cohort, PFS was 5.2 versus 4.7 months (p = 0.207) and OS was 8.4
      versus 6.4 months (p = 0.031) in patients with versus without MGMT promoter
      methylation. Patients with MGMT methylated tumors had longer PFS when treated
      with radiotherapy (RT) plus CT or CT alone compared to patients treated with RT
      alone. Patients with MGMT unmethylated tumors appeared to derive no survival
      benefit from CT, regardless of whether given at diagnosis together with RT or as
      a salvage treatment. Patients treated with RT plus CT or CT alone demonstrated
      longer OS when pyrosequencing revealed >25% MGMT methylated alleles. Taken
      together, MGMT promoter methylation may be a useful biomarker to stratify elderly
      glioblastoma patients for treatment with versus without alkylating agent CT.

PMID- 22139908
TI  - Hepatic steatosis, fibrosis, and cancer in elderly cadavers.
AB  - The incidence of hepatic steatosis, fibrosis, and cancer in the elderly
      population remains unknown. Human cadavers used in anatomy teaching, which come
      largely from older adults, may provide liver tissue for examining their
      pathologies. Livers were obtained from 68 cadavers (mean age 82.1 +/- 10.4 years)
      with diverse causes of death in the Anatomy course at Mount Sinai School of
      Medicine. Paraffin sections were stained with hematoxylin and eosin and Sirius
      red and evaluated for steatosis, fibrosis, cancer, and lipofuscin. Tissue
      preservation was graded as good in 38.2% of the embalmed livers, fair in 36.7%,
      and poor in 25.0%. Steatosis was observed in 35.3% of the livers, central vein
      fibrosis in 49.2%, perisinusoidal fibrosis in 63.2%, portal tract (PT) fibrosis
      in 47.0%, septa formation in 44.1%, bridging fibrosis in 30.8%, and cirrhosis in
      4.4%. One hepatocellular carcinoma (HCC) and six metastatic tumors were detected.
      Lobular inflammation occurred in 20.8% of the livers and PT inflammation in
      38.8%. Nine livers showed minimal change. Lipofuscin was detected in 60.2% of the
      livers. Steatosis, fibrosis, and cancer are highly prevalent in elderly cadavers
      with diverse causes of death. The prevalence of steatosis and fibrosis is
      consistent with the data in patients with specific liver diseases. Steatosis
      alongside fibrosis can accelerate the progression of fibrosis to cirrhosis and
      ultimately HCC. Though not indicated as the primary cause of death, the liver
      injury may have compromised hepatic functions and enhanced disease
      susceptibility, thereby exacerbating the health conditions in this elderly
      population.

PMID- 22139909
TI  - A phase 1 dose-escalation study of ARRY-520, a kinesin spindle protein inhibitor,
      in patients with advanced myeloid leukemias.
AB  - BACKGROUND: ARRY-520 selectively inhibits the mitotic kinesin spindle protein
      (KSP), which leads to abnormal monopolar spindle formation and apoptosis.
      METHODS: A phase 1 trial was conducted to establish the safety and the maximum
      tolerated dose (MTD) of ARRY-520 given as a 1-hour infusion in either a single
      dose or on a day 1, 3, and 5 divided-dose schedule per cycle in patients with
      advanced or refractory myeloid leukemias. Additional objectives were to
      characterize pharmacokinetics, assess preliminary clinical activity, and explore
      biomarkers of KSP inhibition with ARRY-520. A total of 36 patients with acute
      myelogenous leukemia (n = 34) or myelodysplastic syndromes (n = 2) with a median
      age of 66 years (range, 21-88 years) were enrolled: 15 in the single-dose
      schedule (dose levels: 2.5, 3.75, 4.5, and 5.6 mg/m(2)) and 21 in the divided
      dose schedule (dose levels: 0.8, 1.2, 1.5, and 1.8 mg/m(2)/day). RESULTS: The MTD
      was 4.5 mg/m(2) total dose per cycle for both dose schedules. Dose-limiting
      toxicities included mucositis, exfoliative rash, hand-foot syndrome, and
      hyperbilirubinemia. Grades 3 or 4 reversible drug-related myelosuppression were
      observed in 33 of 36 patients. Plasma pharmacokinetic analyses revealed low
      clearance of ARRY-520 (~3 L/hour), a volume of distribution of ~450 L, and a
      median terminal half-life of >90 hours. Monopolar spindles were observed in blood
      mononuclear cells, through use of 4',6-diamidino-2-phenylindole nucleic acid
      stain and antitubulin antibodies. CONCLUSIONS: On the basis of the relative lack
      of clinical activity, further development of ARRY-520 as an antileukemic agent
      was halted. (Clinicaltrials.gov identifier NCT00637052).

PMID- 22139910
TI  - The NCBI Taxonomy database.
AB  - The NCBI Taxonomy database (http://www.ncbi.nlm.nih.gov/taxonomy) is the standard
      nomenclature and classification repository for the International Nucleotide
      Sequence Database Collaboration (INSDC), comprising the GenBank, ENA (EMBL) and
      DDBJ databases. It includes organism names and taxonomic lineages for each of the
      sequences represented in the INSDC's nucleotide and protein sequence databases.
      The taxonomy database is manually curated by a small group of scientists at the
      NCBI who use the current taxonomic literature to maintain a phylogenetic taxonomy
      for the source organisms represented in the sequence databases. The taxonomy
      database is a central organizing hub for many of the resources at the NCBI, and
      provides a means for clustering elements within other domains of NCBI web site,
      for internal linking between domains of the Entrez system and for linking out to
      taxon-specific external resources on the web. Our primary purpose is to index the
      domain of sequences as conveniently as possible for our user community.

PMID- 22139911
TI  - neXtProt: a knowledge platform for human proteins.
AB  - neXtProt (http://www.nextprot.org/) is a new human protein-centric knowledge
      platform. Developed at the Swiss Institute of Bioinformatics (SIB), it aims to
      help researchers answer questions relevant to human proteins. To achieve this
      goal, neXtProt is built on a corpus containing both curated knowledge originating
      from the UniProtKB/Swiss-Prot knowledgebase and carefully selected and filtered
      high-throughput data pertinent to human proteins. This article presents an
      overview of the database and the data integration process. We also lay out the
      key future directions of neXtProt that we consider the necessary steps to make
      neXtProt the one-stop-shop for all research projects focusing on human proteins.

PMID- 22139913
TI  - GeoPCA: a new tool for multivariate analysis of dihedral angles based on
      principal component geodesics.
AB  - The GeoPCA package is the first tool developed for multivariate analysis of
      dihedral angles based on principal component geodesics. Principal component
      geodesic analysis provides a natural generalization of principal component
      analysis for data distributed in non-Euclidean space, as in the case of angular
      data. GeoPCA presents projection of angular data on a sphere composed of the
      first two principal component geodesics, allowing clustering based on dihedral
      angles as opposed to Cartesian coordinates. It also provides a measure of the
      similarity between input structures based on only dihedral angles, in analogy to
      the root-mean-square deviation of atoms based on Cartesian coordinates. The
      principal component geodesic approach is shown herein to reproduce clusters of
      nucleotides observed in an eta-theta plot. GeoPCA can be accessed via
      http://pca.limlab.ibms.sinica.edu.tw.

PMID- 22139912
TI  - Mre11 modulates the fidelity of fusion between short telomeres in human cells.
AB  - The loss of telomere function can result in the fusion of telomeres with other
      telomeric loci, or non-telomeric double-stranded DNA breaks. Sequence analysis of
      fusion events between short dysfunctional telomeres in human cells has revealed
      that fusion is characterized by a distinct molecular signature consisting of
      extensive deletions and micro-homology at the fusion points. This signature is
      consistent with alternative error-prone end-joining processes. We have examined
      the role that Mre11 may play in the fusion of short telomeres in human cells; to
      do this, we have analysed telomere fusion events in cells derived from ataxia
      telangiectasia-like disorder (ATLD) patients that exhibit hypomorphic mutations
      in MRE11. The telomere dynamics of ATLD fibroblasts were indistinguishable from
      wild-type fibroblasts and they were proficient in the fusion of short telomeres.
      However, we observed a high frequency of insertion of DNA sequences at the fusion
      points that created localized sequence duplications. These data indicate that
      Mre11 plays a role in the fusion of short dysfunctional telomeres in human cells
      and are consistent with the hypothesis that as part of the MRN complex it serves
      to stabilize the joining complex, thereby controlling the fidelity of the fusion
      reaction.

PMID- 22139914
TI  - MOPED: Model Organism Protein Expression Database.
AB  - Large numbers of mass spectrometry proteomics studies are being conducted to
      understand all types of biological processes. The size and complexity of
      proteomics data hinders efforts to easily share, integrate, query and compare the
      studies. The Model Organism Protein Expression Database (MOPED,
      htttp://moped.proteinspire.org) is a new and expanding proteomics resource that
      enables rapid browsing of protein expression information from publicly available
      studies on humans and model organisms. MOPED is designed to simplify the
      comparison and sharing of proteomics data for the greater research community.
      MOPED uniquely provides protein level expression data, meta-analysis capabilities
      and quantitative data from standardized analysis. Data can be queried for
      specific proteins, browsed based on organism, tissue, localization and condition
      and sorted by false discovery rate and expression. MOPED empowers users to
      visualize their own expression data and compare it with existing studies.
      Further, MOPED links to various protein and pathway databases, including
      GeneCards, Entrez, UniProt, KEGG and Reactome. The current version of MOPED
      contains over 43,000 proteins with at least one spectral match and more than 11
      million high certainty spectra.

PMID- 22139915
TI  - The telomeric transcriptome of Schizosaccharomyces pombe.
AB  - Eukaryotic telomeres are transcribed into telomeric repeat-containing RNA
      (TERRA). Telomeric transcription has been documented in mammals, birds, zebra
      fish, plants and budding yeast. Here we show that the chromosome ends of
      Schizosaccharomyces pombe produce distinct RNA species. As with budding yeast and
      mammals, S. pombe contains G-rich TERRA molecules and subtelomeric RNA species
      transcribed in the opposite direction of TERRA (ARRET). Moreover, fission yeast
      chromosome ends produce two novel RNA species: C-rich telomeric repeat-containing
      transcripts (ARIA) and subtelomeric transcripts complementary to ARRET
      (alphaARRET). RNA polymerase II (RNAPII) associates with pombe chromosome ends in
      vivo and the telomeric factor Rap1 negatively regulates this association, as well
      as the cellular accumulation of RNA emanating from chromosome ends. We also show
      that the RNAPII subunit Rpb7 and the non-canonical poly(A) polymerases Cid12 and
      Cid14 are involved in the regulation of TERRA, ARIA, ARRET and alphaARRET
      transcripts. We confirm the evolutionary conservation of telomere transcription,
      and reveal intriguing similarities and differences in the composition and
      regulation of telomeric transcripts among model organisms.

PMID- 22139916
TI  - VIRsiRNAdb: a curated database of experimentally validated viral siRNA/shRNA.
AB  - RNAi technology has been emerging as a potential modality to inhibit viruses
      during past decade. In literature a few siRNA databases have been reported that
      focus on targeting human and mammalian genes but experimentally validated viral
      siRNA databases are lacking. We have developed VIRsiRNAdb, a manually curated
      database having comprehensive details of 1358 siRNA/shRNA targeting viral genome
      regions. Further, wherever available, information regarding alternative
      efficacies of above 300 siRNAs derived from different assays has also been
      incorporated. Important fields included in the database are siRNA sequence, virus
      subtype, target genome region, cell type, target object, experimental assay,
      efficacy, off-target and siRNA matching with reference viral sequences. Database
      also provides the users with facilities of advance search, browsing, data
      submission, linking to external databases and useful siRNA analysis tools
      especially siTarAlign which align the siRNA with reference viral genomes or user
      defined sequences. VIRsiRNAdb contains extensive details of siRNA/shRNA targeting
      42 important human viruses including influenza virus, hepatitis B virus, HPV and
      SARS Corona virus. VIRsiRNAdb would prove useful for researchers in picking up
      the best viral siRNA for antiviral therapeutics development and also for
      developing better viral siRNA design tools. The database is freely available at
      http://crdd.osdd.net/servers/virsirnadb.

PMID- 22139917
TI  - Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal
      differentiation by alternative polyadenylation.
AB  - The ubiquitously expressed RNA-binding protein HuR increases the stability and
      translation of mRNAs encoding growth regulatory proteins that promote
      proliferation in a variety of cell types. However, the three neuron-specific
      ELAV/Hu proteins, HuB, HuC and HuD, while binding to the same types of mRNAs, are
      required instead for neuronal differentiation, and it becomes difficult to
      reconcile these contrary functions when all four Hu proteins are expressed in the
      same neuron. HuR mRNA exists as three alternatively polyadenylated variants, a
      1.5-kb testes-specific mRNA isoform, a ubiquitous 2.4-kb isoform and a 6.0-kb
      isoform that we now show is induced during neuronal differentiation and appears
      to be neuron-specific. This 6.0-kb neuron-specific mRNA isoform is inherently
      less stable and produces less HuR protein than the ubiquitous 2.4-kb mRNA.
      Furthermore, we show that neuronal HuB, HuC and HuD, as well as HuR itself, can
      bind at the 2.4-kb mRNA polyadenylation site, and when overexpressed can affect
      alternative polyadenylation to generate an extended HuR 3'-UTR that is
      translationally suppressed. We propose that the regulation of HuR protein
      expression by alternative polyadenylation allows neurons to post
      transcriptionally regulate mRNAs-encoding factors required for proliferation
      versus differentiation to facilitate neuronal differentiation.

PMID- 22139918
TI  - AutismKB: an evidence-based knowledgebase of autism genetics.
AB  - Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder
      with a prevalence of 0.9-2.6%. Twin studies showed a heritability of 38-90%,
      indicating strong genetic contributions. Yet it is unclear how many genes have
      been associated with ASD and how strong the evidence is. A comprehensive review
      and analysis of literature and data may bring a clearer big picture of autism
      genetics. We show that as many as 2193 genes, 2806 SNPs/VNTRs, 4544 copy number
      variations (CNVs) and 158 linkage regions have been associated with ASD by GWAS,
      genome-wide CNV studies, linkage analyses, low-scale genetic association studies,
      expression profiling and other low-scale experimental studies. To evaluate the
      evidence, we collected metadata about each study including clinical and
      demographic features, experimental design and statistical significance, and used
      a scoring and ranking approach to select a core data set of 434 high-confidence
      genes. The genes mapped to pathways including neuroactive ligand-receptor
      interaction, synapse transmission and axon guidance. To better understand the
      genes we parsed over 30 databases to retrieve extensive data about expression
      patterns, protein interactions, animal models and pharmacogenetics. We
      constructed a MySQL-based online database and share it with the broader autism
      research community at http://autismkb.cbi.pku.edu.cn, supporting sophisticated
      browsing and searching functionalities.

PMID- 22139919
TI  - Nematode.net update 2011: addition of data sets and tools featuring next
      generation sequencing data.
AB  - Nematode.net (http://nematode.net) has been a publicly available resource for
      studying nematodes for over a decade. In the past 3 years, we reorganized
      Nematode.net to provide more user-friendly navigation through the site, a
      necessity due to the explosion of data from next-generation sequencing platforms.
      Organism-centric portals containing dynamically generated data are available for
      over 56 different nematode species. Next-generation data has been added to the
      various data-mining portals hosted, including NemaBLAST and NemaBrowse. The
      NemaPath metabolic pathway viewer builds associations using KOs, rather than ECs
      to provide more accurate and fine-grained descriptions of proteins. Two new
      features for data analysis and comparative genomics have been added to the site.
      NemaSNP enables the user to perform population genetics studies in various
      nematode populations using next-generation sequencing data. HelmCoP (Helminth
      Control and Prevention) as an independent component of Nematode.net provides an
      integrated resource for storage, annotation and comparative genomics of helminth
      genomes to aid in learning more about nematode genomes, as well as drug,
      pesticide, vaccine and drug target discovery. With this update, Nematode.net will
      continue to realize its original goal to disseminate diverse bioinformatic data
      sets and provide analysis tools to the broad scientific community in a useful and
      user-friendly manner.

PMID- 22139920
TI  - SitEx: a computer system for analysis of projections of protein functional sites
      on eukaryotic genes.
AB  - Search of interrelationships between the structural-functional protein
      organization and exon structure of encoding gene provides insights into issues
      concerned with the function, origin and evolution of genes and proteins. The
      functions of proteins and their domains are defined mostly by functional sites.
      The relation of the exon-intron structure of the gene to the protein functional
      sites has been little studied. Development of resources containing data on
      projections of protein functional sites on eukaryotic genes is needed. We have
      developed SitEx, a database that contains information on functional site amino
      acid positions in the exon structure of encoding gene. SitEx is integrated with
      the BLAST and 3DExonScan programs. BLAST is used for searching sequence
      similarity between the query protein and polypeptides encoded by single exons
      stored in SitEx. The 3DExonScan program is used for searching for structural
      similarity of the given protein with these polypeptides using superimpositions.
      The developed computer system allows users to analyze the coding features of
      functional sites by taking into account the exon structure of the gene, to detect
      the exons involved in shuffling in protein evolution, also to design protein
      engineering experiments. SitEx is accessible at http://www-bionet.sscc.ru/sitex/.
      Currently, it contains information about 9994 functional sites presented in 2021
      proteins described in proteomes of 17 organisms.

PMID- 22139921
TI  - Improved systematic tRNA gene annotation allows new insights into the evolution
      of mitochondrial tRNA structures and into the mechanisms of mitochondrial genome
      rearrangements.
AB  - Transfer RNAs (tRNAs) are present in all types of cells as well as in organelles.
      tRNAs of animal mitochondria show a low level of primary sequence conservation
      and exhibit 'bizarre' secondary structures, lacking complete domains of the
      common cloverleaf. Such sequences are hard to detect and hence frequently missed
      in computational analyses and mitochondrial genome annotation. Here, we introduce
      an automatic annotation procedure for mitochondrial tRNA genes in Metazoa based
      on sequence and structural information in manually curated covariance models. The
      method, applied to re-annotate 1876 available metazoan mitochondrial RefSeq
      genomes, allows to distinguish between remaining functional genes and degrading
      'pseudogenes', even at early stages of divergence. The subsequent analysis of a
      comprehensive set of mitochondrial tRNA genes gives new insights into the
      evolution of structures of mitochondrial tRNA sequences as well as into the
      mechanisms of genome rearrangements. We find frequent losses of tRNA genes
      concentrated in basal Metazoa, frequent independent losses of individual parts of
      tRNA genes, particularly in Arthropoda, and wide-spread conserved overlaps of
      tRNAs in opposite reading direction. Direct evidence for several recent Tandem
      Duplication-Random Loss events is gained, demonstrating that this mechanism has
      an impact on the appearance of new mitochondrial gene orders.

PMID- 22139922
TI  - Non-coding telomeric and subtelomeric transcripts are differentially regulated by
      telomeric and heterochromatin assembly factors in fission yeast.
AB  - While telomere repeat-containing non-coding RNA has been identified in a variety
      of eukaryotes, its biological role is not yet clear. We have identified telomeric
      transcripts in fission yeast, a model system that combines precise genetic
      manipulability with telomeres remarkably similar to those of human. Like human
      and budding yeast, fission yeast harbours a population of telomeric RNA molecules
      containing G-rich telomeric repeats transcribed from the subtelomere to the
      telomere. In addition, we detect substantial levels of C-rich telomeric RNA whose
      appearance is independent of the RNA-dependent RNA polymerase, suggesting that
      the telomere repeats themselves serve as promoter sites; multiple distinct
      subtelomeric RNAs are also present. The regulation of these transcripts depends
      on the telomere-associated proteins Taz1 and Rap1, as deletion of taz1(+) or
      rap1(+) leads to increased levels of both telomere repeat-containing and
      subtelomeric transcripts. In contrast, loss of the heterochromatin proteins Swi6
      or Clr4 or the telomerase regulator Rif1 results in elevated subtelomeric RNA
      levels while telomere-repeat containing transcript levels remain repressed.
      Coupled with the large body of knowledge surrounding the functions of telomeric
      and heterochromatin factors in fission yeast, these in vivo analyses suggest
      testable models for the roles of TERRA in telomere function.

PMID- 22139923
TI  - Modulation of CRISPR locus transcription by the repeat-binding protein Cbp1 in
      Sulfolobus.
AB  - CRISPR loci are essential components of the adaptive immune system of archaea and
      bacteria. They consist of long arrays of repeats separated by DNA spacers
      encoding guide RNAs (crRNA), which target foreign genetic elements. Cbp1 (CRISPR
      DNA repeat binding protein) binds specifically to the multiple direct repeats of
      CRISPR loci of members of the acidothermophilic, crenarchaeal order Sulfolobales.
      cbp1 gene deletion from Sulfolobus islandicus REY15A produced a strong reduction
      in pre-crRNA yields from CRISPR loci but did not inhibit the foreign DNA
      targeting capacity of the CRISPR/Cas system. Conversely, overexpression of Cbp1
      in S. islandicus generated an increase in pre-crRNA yields while the level of
      reverse strand transcripts from CRISPR loci remained unchanged. It is proposed
      that Cbp1 modulates production of longer pre-crRNA transcripts from CRISPR loci.
      A possible mechanism is that it minimizes interference from potential
      transcriptional signals carried on spacers deriving from A-T-rich genetic
      elements and, occasionally, on DNA repeats. Supporting evidence is provided by
      microarray and northern blotting analyses, and publicly available whole
      transcriptome data for S. solfataricus P2.

PMID- 22139924
TI  - An in silico model for identification of small RNAs in whole bacterial genomes:
      characterization of antisense RNAs in pathogenic Escherichia coli and
      Streptococcus agalactiae strains.
AB  - Characterization of small non-coding ribonucleic acids (sRNA) among the large
      volume of data generated by high-throughput RNA-seq or tiling microarray analyses
      remains a challenge. Thus, there is still a need for accurate in silico
      prediction methods to identify sRNAs within a given bacterial species. After
      years of effort, dedicated software were developed based on comparative genomic
      analyses or mathematical/statistical models. Although these genomic analyses
      enabled sRNAs in intergenic regions to be efficiently identified, they all failed
      to predict antisense sRNA genes (asRNA), i.e. RNA genes located on the DNA strand
      complementary to that which encodes the protein. The statistical models enabled
      any genomic region to be analyzed theorically but not efficiently. We present a
      new model for in silico identification of sRNA and asRNA candidates within an
      entire bacterial genome. This model was successfully used to analyze the Gram
      negative Escherichia coli and Gram-positive Streptococcus agalactiae. In both
      bacteria, numerous asRNAs are transcribed from the complementary strand of genes
      located in pathogenicity islands, strongly suggesting that these asRNAs are
      regulators of the virulence expression. In particular, we characterized an asRNA
      that acted as an enhancer-like regulator of the type 1 fimbriae production
      involved in the virulence of extra-intestinal pathogenic E. coli.

PMID- 22139925
TI  - GWASdb: a database for human genetic variants identified by genome-wide
      association studies.
AB  - Recent advances in genome-wide association studies (GWAS) have enabled us to
      identify thousands of genetic variants (GVs) that are associated with human
      diseases. As next-generation sequencing technologies become less expensive, more
      GVs will be discovered in the near future. Existing databases, such as NHGRI GWAS
      Catalog, collect GVs with only genome-wide level significance. However, many true
      disease susceptibility loci have relatively moderate P values and are not
      included in these databases. We have developed GWASdb that contains 20 times more
      data than the GWAS Catalog and includes less significant GVs (P < 1.0 * 10(-3))
      manually curated from the literature. In addition, GWASdb provides comprehensive
      functional annotations for each GV, including genomic mapping information,
      regulatory effects (transcription factor binding sites, microRNA target sites and
      splicing sites), amino acid substitutions, evolution, gene expression and disease
      associations. Furthermore, GWASdb classifies these GVs according to diseases
      using Disease-Ontology Lite and Human Phenotype Ontology. It can conduct pathway
      enrichment and PPI network association analysis for these diseases. GWASdb
      provides an intuitive, multifunctional database for biologists and clinicians to
      explore GVs and their functional inferences. It is freely available at
      http://jjwanglab.org/gwasdb and will be updated frequently.

PMID- 22139926
TI  - The N-terminal domains of TRF1 and TRF2 regulate their ability to condense
      telomeric DNA.
AB  - TRF1 and TRF2 are key proteins in human telomeres, which, despite their
      similarities, have different behaviors upon DNA binding. Previous work has shown
      that unlike TRF1, TRF2 condenses telomeric, thus creating consequential negative
      torsion on the adjacent DNA, a property that is thought to lead to the
      stimulation of single-strand invasion and was proposed to favor telomeric DNA
      looping. In this report, we show that these activities, originating from the
      central TRFH domain of TRF2, are also displayed by the TRFH domain of TRF1 but
      are repressed in the full-length protein by the presence of an acidic domain at
      the N-terminus. Strikingly, a similar repression is observed on TRF2 through the
      binding of a TERRA-like RNA molecule to the N-terminus of TRF2. Phylogenetic and
      biochemical studies suggest that the N-terminal domains of TRF proteins originate
      from a gradual extension of the coding sequences of a duplicated ancestral gene
      with a consequential progressive alteration of the biochemical properties of
      these proteins. Overall, these data suggest that the N-termini of TRF1 and TRF2
      have evolved to finely regulate their ability to condense DNA.

PMID- 22139927
TI  - MetaBase--the wiki-database of biological databases.
AB  - Biology is generating more data than ever. As a result, there is an ever
      increasing number of publicly available databases that analyse, integrate and
      summarize the available data, providing an invaluable resource for the biological
      community. As this trend continues, there is a pressing need to organize,
      catalogue and rate these resources, so that the information they contain can be
      most effectively exploited. MetaBase (MB) (http://MetaDatabase.Org) is a
      community-curated database containing more than 2000 commonly used biological
      databases. Each entry is structured using templates and can carry various user
      comments and annotations. Entries can be searched, listed, browsed or queried.
      The database was created using the same MediaWiki technology that powers
      Wikipedia, allowing users to contribute on many different levels. The initial
      release of MB was derived from the content of the 2007 Nucleic Acids Research
      (NAR) Database Issue. Since then, approximately 100 databases have been manually
      collected from the literature, and users have added information for over 240
      databases. MB is synchronized annually with the static Molecular Biology Database
      Collection provided by NAR. To date, there have been 19 significant contributors
      to the project; each one is listed as an author here to highlight the community
      aspect of the project.

PMID- 22139928
TI  - SpliceDisease database: linking RNA splicing and disease.
AB  - RNA splicing is an important aspect of gene regulation in many organisms.
      Splicing of RNA is regulated by complicated mechanisms involving numerous RNA
      binding proteins and the intricate network of interactions among them. Mutations
      in cis-acting splicing elements or its regulatory proteins have been shown to be
      involved in human diseases. Defects in pre-mRNA splicing process have emerged as
      a common disease-causing mechanism. Therefore, a database integrating RNA
      splicing and disease associations would be helpful for understanding not only the
      RNA splicing but also its contribution to disease. In SpliceDisease database, we
      manually curated 2337 splicing mutation disease entries involving 303 genes and
      370 diseases, which have been supported experimentally in 898 publications. The
      SpliceDisease database provides information including the change of the
      nucleotide in the sequence, the location of the mutation on the gene, the
      reference Pubmed ID and detailed description for the relationship among gene
      mutations, splicing defects and diseases. We standardized the names of the
      diseases and genes and provided links for these genes to NCBI and UCSC genome
      browser for further annotation and genomic sequences. For the location of the
      mutation, we give direct links of the entry to the respective position/region in
      the genome browser. The users can freely browse, search and download the data in
      SpliceDisease at http://cmbi.bjmu.edu.cn/sdisease.

PMID- 22139929
TI  - BioProject and BioSample databases at NCBI: facilitating capture and organization
      of metadata.
AB  - As the volume and complexity of data sets archived at NCBI grow rapidly, so does
      the need to gather and organize the associated metadata. Although metadata has
      been collected for some archival databases, previously, there was no centralized
      approach at NCBI for collecting this information and using it across databases.
      The BioProject database was recently established to facilitate organization and
      classification of project data submitted to NCBI, EBI and DDBJ databases. It
      captures descriptive information about research projects that result in high
      volume submissions to archival databases, ties together related data across
      multiple archives and serves as a central portal by which to inform users of data
      availability. Concomitantly, the BioSample database is being developed to capture
      descriptive information about the biological samples investigated in projects.
      BioProject and BioSample records link to corresponding data stored in archival
      repositories. Submissions are supported by a web-based Submission Portal that
      guides users through a series of forms for input of rich metadata describing
      their projects and samples. Together, these databases offer improved ways for
      users to query, locate, integrate and interpret the masses of data held in NCBI's
      archival repositories. The BioProject and BioSample databases are available at
      http://www.ncbi.nlm.nih.gov/bioproject and http://www.ncbi.nlm.nih.gov/biosample,
      respectively.

PMID- 22139930
TI  - The orientation of the C-terminal domain of the Saccharomyces cerevisiae Rap1
      protein is determined by its binding to DNA.
AB  - Rap1 is an essential DNA-binding factor from the yeast Saccharomyces cerevisiae
      involved in transcription and telomere maintenance. Its binding to DNA targets
      Rap1 at particular loci, and may optimize its ability to form functional
      macromolecular assemblies. It is a modular protein, rich in large potentially
      unfolded regions, and comprising BRCT, Myb and RCT well-structured domains. Here,
      we present the architectures of Rap1 and a Rap1/DNA complex, built through a step
      by-step integration of small angle X-ray scattering, X-ray crystallography and
      nuclear magnetic resonance data. Our results reveal Rap1 structural adjustment
      upon DNA binding that involves a specific orientation of the C-terminal (RCT)
      domain with regard to the DNA binding domain (DBD). Crystal structure of DBD in
      complex with a long DNA identifies an essential wrapping loop, which constrains
      the orientation of the RCT and affects Rap1 affinity to DNA. Based on our
      structural information, we propose a model for Rap1 assembly at telomere.

PMID- 22139931
TI  - Multiple conformations of SAM-II riboswitch detected with SAXS and NMR
      spectroscopy.
AB  - Riboswitches are a newly discovered large family of structured functional RNA
      elements that specifically bind small molecule targets out of a myriad of
      cellular metabolites to modulate gene expression. Structural studies of ligand
      bound riboswitches by X-ray crystallography and nuclear magnetic resonance (NMR)
      spectroscopy have provided insights into detailed RNA-ligand recognition and
      interactions. However, the structures of ligand-free riboswitches remain poorly
      characterized. In this study, we have used a variety of biochemical, biophysical
      and computational techniques including small-angle X-ray scattering and NMR
      spectroscopy to characterize the ligand-free and ligand-bound forms of SAM-II
      riboswitch. Our data demonstrate that the RNA adopts multiple conformations along
      its folding pathway and suggest that the RNA undergoes marked conformational
      changes upon Mg(2+) compaction and S-adenosylmethionine (SAM) metabolite binding.
      Further studies indicated that Mg(2+) ion is not essential for the ligand binding
      but can stabilize the complex by facilitating loop/stem interactions. In the
      presence of millimolar concentration of Mg(2+) ion, the RNA samples a more
      compact conformation. This conformation is near to, but distinct from, the native
      fold and competent to bind the metabolite. We conclude that the formation of
      various secondary and tertiary structural elements, including a pseudoknot, occur
      to sequester the putative Shine-Dalgarno sequence of the RNA only after
      metabolite binding.

PMID- 22139932
TI  - HmtDB, a genomic resource for mitochondrion-based human variability studies.
AB  - HmtDB (http://www.hmtdb.uniba.it:8080/hmdb) is a open resource created to support
      population genetics and mitochondrial disease studies. The database hosts human
      mitochondrial genome sequences annotated with population and variability data,
      the latter being estimated through the application of the SiteVar software based
      on site-specific nucleotide and amino acid variability calculations. The
      annotations are manually curated thus adding value to the quality of the
      information provided to the end-user. Classifier tools implemented in HmtDB allow
      the prediction of the haplogroup for any human mitochondrial genome currently
      stored in HmtDB or externally submitted de novo by an end-user. Haplogroup
      definition is based on the Phylotree system. End-users accessing HmtDB are hence
      allowed to (i) browse the database through the use of a multi-criterion 'query'
      system; (ii) analyze their own human mitochondrial sequences via the 'classify'
      tool (for complete genomes) or by downloading the 'fragment-classifier' tool (for
      partial sequences); (iii) download multi-alignments with reference genomes as
      well as variability data.

PMID- 22139933
TI  - IGDB.NSCLC: integrated genomic database of non-small cell lung cancer.
AB  - Lung cancer is the most common cause of cancer-related mortality with more than
      1.4 million deaths per year worldwide. To search for significant somatic
      alterations in lung cancer, we analyzed, integrated and manually curated various
      data sets and literatures to present an integrated genomic database of non-small
      cell lung cancer (IGDB.NSCLC, http://igdb.nsclc.ibms.sinica.edu.tw). We collected
      data sets derived from hundreds of human NSCLC (lung adenocarcinomas and/or
      squamous cell carcinomas) to illustrate genomic alterations [chromosomal regions
      with copy number alterations (CNAs), gain/loss and loss of heterozygosity],
      aberrant expressed genes and microRNAs, somatic mutations and experimental
      evidence and clinical information of alterations retrieved from literatures.
      IGDB.NSCLC provides user friendly interfaces and searching functions to display
      multiple layers of evidence especially emphasizing on concordant alterations of
      CNAs with co-localized altered gene expression, aberrant microRNAs expression,
      somatic mutations or genes with associated clinicopathological features. These
      significant concordant alterations in NSCLC are graphically or tabularly
      presented to facilitate and prioritize as the putative cancer targets for
      pathological and mechanistic studies of lung tumorigenesis and for developing new
      strategies in clinical interventions.

PMID- 22139934
TI  - Cube-DB: detection of functional divergence in human protein families.
AB  - Cube-DB is a database of pre-evaluated results for detection of functional
      divergence in human/vertebrate protein families. The analysis is organized around
      the nomenclature associated with the human proteins, but based on all currently
      available vertebrate genomes. Using full genomes enables us, through a mutual
      best-hit strategy, to construct comparable taxonomical samples for all paralogues
      under consideration. Functional specialization is scored on the residue level
      according to two models of behavior after divergence: heterotachy and homotachy.
      In the first case, the positions on the protein sequence are scored highly if
      they are conserved in the reference group of orthologs, and overlap poorly with
      the residue type choice in the paralogs groups (such positions will also be
      termed functional determinants). The second model additionally requires
      conservation within each group of paralogs (functional discriminants). The
      scoring functions are phylogeny independent, but sensitive to the residue type
      similarity. The results are presented as a table of per-residue scores, and
      mapped onto related structure (when available) via browser-embedded visualization
      tool. They can also be downloaded as a spreadsheet table, and sessions for two
      additional molecular visualization tools. The database interface is available at
      http://epsf.bmad.bii.a-star.edu.sg/cube/db/html/home.html.

PMID- 22139935
TI  - GReEn: a tool for efficient compression of genome resequencing data.
AB  - Research in the genomic sciences is confronted with the volume of sequencing and
      resequencing data increasing at a higher pace than that of data storage and
      communication resources, shifting a significant part of research budgets from the
      sequencing component of a project to the computational one. Hence, being able to
      efficiently store sequencing and resequencing data is a problem of paramount
      importance. In this article, we describe GReEn (Genome Resequencing Encoding), a
      tool for compressing genome resequencing data using a reference genome sequence.
      It overcomes some drawbacks of the recently proposed tool GRS, namely, the
      possibility of compressing sequences that cannot be handled by GRS, faster
      running times and compression gains of over 100-fold for some sequences. This
      tool is freely available for non-commercial use at
      ftp://ftp.ieeta.pt/~ap/codecs/GReEn1.tar.gz.

PMID- 22139936
TI  - Short non-coding RNA fragments accumulating in chloroplasts: footprints of RNA
      binding proteins?
AB  - Chloroplast RNA metabolism is controlled and excecuted by hundreds of nuclear
      encoded, chloroplast-localized RNA binding proteins. Contrary to the nucleo
      cytosolic compartment or bacteria, there is little evidence for non-coding RNAs
      that play a role as riboregulators of chloroplasts. We mined deep-sequencing
      datasets to identify short (16-28 nt) RNAs in the chloroplast genome and found 50
      abundant small RNAs (sRNAs) represented by multiple, in some cases, thousands of
      sequencing reads, whereas reads are in general absent from the surrounding
      sequence space. Other than sRNAs representing the most highly abundant mRNAs,
      tRNAs and rRNAs, most sRNAs are located in non-coding regions and many are found
      a short distance upstream of start codons. By transcript end mapping we show that
      the 5' and 3' termini of chloroplast RNAs coincide with the ends of sRNAs.
      Sequences of sRNAs identified in Arabidopsis are conserved between different
      angiosperm species and in several cases, we identified putative orthologs in rice
      deep sequencing datasets. Recently, it was suggested that small chloroplast RNA
      fragments could result from the protective action of pentatricopeptide repeat
      (PPR) proteins against exonucleases, i.e. footprints of RNA binding proteins. Our
      data support this scenario on a transcriptome-wide level and suggest that a large
      number of sRNAs are in fact remnants of PPR protein targets.

PMID- 22139937
TI  - NRG-CING: integrated validation reports of remediated experimental biomolecular
      NMR data and coordinates in wwPDB.
AB  - For many macromolecular NMR ensembles from the Protein Data Bank (PDB) the
      experiment-based restraint lists are available, while other experimental data,
      mainly chemical shift values, are often available from the BioMagResBank. The
      accuracy and precision of the coordinates in these macromolecular NMR ensembles
      can be improved by recalculation using the available experimental data and
      present-day software. Such efforts, however, generally fail on half of all NMR
      ensembles due to the syntactic and semantic heterogeneity of the underlying data
      and the wide variety of formats used for their deposition. We have combined the
      remediated restraint information from our NMR Restraints Grid (NRG) database with
      available chemical shifts from the BioMagResBank and the Common Interface for NMR
      structure Generation (CING) structure validation reports into the weekly updated
      NRG-CING database (http://nmr.cmbi.ru.nl/NRG-CING). Eleven programs have been
      included in the NRG-CING production pipeline to arrive at validation reports that
      list for each entry the potential inconsistencies between the coordinates and the
      available experimental NMR data. The longitudinal validation of these data in a
      publicly available relational database yields a set of indicators that can be
      used to judge the quality of every macromolecular structure solved with NMR. The
      remediated NMR experimental data sets and validation reports are freely available
      online.

PMID- 22139938
TI  - Gene3D: a domain-based resource for comparative genomics, functional annotation
      and protein network analysis.
AB  - Gene3D http://gene3d.biochem.ucl.ac.uk is a comprehensive database of protein
      domain assignments for sequences from the major sequence databases. Domains are
      directly mapped from structures in the CATH database or predicted using a library
      of representative profile HMMs derived from CATH superfamilies. As previously
      described, Gene3D integrates many other protein family and function databases.
      These facilitate complex associations of molecular function, structure and
      evolution. Gene3D now includes a domain functional family (FunFam) level below
      the homologous superfamily level assignments. Additions have also been made to
      the interaction data. More significantly, to help with the visualization and
      interpretation of multi-genome scale data sets, we have developed a new, revamped
      website. Searching has been simplified with more sophisticated filtering of
      results, along with new tools based on Cytoscape Web, for visualizing protein
      protein interaction networks, differences in domain composition between genomes
      and the taxonomic distribution of individual superfamilies.

PMID- 22139939
TI  - ccPDB: compilation and creation of data sets from Protein Data Bank.
AB  - ccPDB (http://crdd.osdd.net/raghava/ccpdb/) is a database of data sets compiled
      from the literature and Protein Data Bank (PDB). First, we collected and compiled
      data sets from the literature used for developing bioinformatics methods to
      annotate the structure and function of proteins. Second, data sets were derived
      from the latest release of PDB using standard protocols. Third, we developed a
      powerful module for creating a wide range of customized data sets from the
      current release of PDB. This is a flexible module that allows users to create
      data sets using a simple six step procedure. In addition, a number of web
      services have been integrated in ccPDB, which include submission of jobs on PDB
      based servers, annotation of protein structures and generation of patterns. This
      database maintains >30 types of data sets such as secondary structure, tight
      turns, nucleotide interacting residues, metals interacting residues, DNA/RNA
      binding residues and so on.

PMID- 22139940
TI  - Statistical evaluation of improvement in RNA secondary structure prediction.
AB  - With discovery of diverse roles for RNA, its centrality in cellular functions has
      become increasingly apparent. A number of algorithms have been developed to
      predict RNA secondary structure. Their performance has been benchmarked by
      comparing structure predictions to reference secondary structures. Generally,
      algorithms are compared against each other and one is selected as best without
      statistical testing to determine whether the improvement is significant. In this
      work, it is demonstrated that the prediction accuracies of methods correlate with
      each other over sets of sequences. One possible reason for this correlation is
      that many algorithms use the same underlying principles. A set of benchmarks
      published previously for programs that predict a structure common to three or
      more sequences is statistically analyzed as an example to show that it can be
      rigorously evaluated using paired two-sample t-tests. Finally, a pipeline of
      statistical analyses is proposed to guide the choice of data set size and
      performance assessment for benchmarks of structure prediction. The pipeline is
      applied using 5S rRNA sequences as an example.

PMID- 22139941
TI  - MMMDB: Mouse Multiple Tissue Metabolome Database.
AB  - The Mouse Multiple Tissue Metabolome Database (MMMDB) provides comprehensive and
      quantitative metabolomic information for multiple tissues from single mice.
      Manually curated databases that integrate literature-based individual metabolite
      information have been available so far. However, data sets on the absolute
      concentration of a single metabolite integrated from multiple resources are often
      difficult to be used when different metabolomic studies are compared because the
      relative balance of the multiple metabolite concentrations in the metabolic
      pathways as a snapshot of a dynamic system is more important than the absolute
      concentration of a single metabolite. We developed MMMDB by performing non
      targeted analyses of cerebra, cerebella, thymus, spleen, lung, liver, kidney,
      heart, pancreas, testis and plasma using capillary electrophoresis time-of-flight
      mass spectrometry and detected 428 non-redundant features from which 219
      metabolites were successfully identified. Quantified concentrations of the
      individual metabolites and the corresponding processed raw data; for example, the
      electropherograms and mass spectra with their annotations, such as isotope and
      fragment information, are stored in the database. MMMDB is designed to normalize
      users' data, which can be submitted online and used to visualize overlaid
      electropherograms. Thus, MMMDB allows newly measured data to be compared with the
      other data in the database. MMMDB is available at: http://mmmdb.iab.keio.ac.jp.

PMID- 22139942
TI  - RecountDB: a database of mapped and count corrected transcribed sequences.
AB  - The field of gene expression analysis continues to benefit from next-generation
      sequencing generated data, which enables transcripts to be measured with
      unmatched accuracy and resolution. But the high-throughput reads from these
      technologies also contain many errors, which can compromise the ability to
      accurately detect and quantify rare transcripts. Fortunately, techniques exist to
      ameliorate the affects of sequencer error. We present RecountDB, a secondary
      database derived from primary data in NCBI's short read archive. RecountDB holds
      sequence counts from RNA-seq and 5' capped transcription start site experiments,
      corrected and mapped to the relevant genome. Via a searchable and browseable
      interface users can obtain corrected data in formats useful for transcriptomic
      analysis. The database is currently populated with 2265 entries from 45 organisms
      and continuously growing. RecountDB is publicly available at:
      http://recountdb.cbrc.jp.

PMID- 22139943
TI  - Production of transgenic calves expressing an shRNA targeting myostatin.
AB  - Myostatin (MSTN) is a well-known negative regulator of muscle growth. Animals
      that possess mutations within this gene display an enhanced muscling phenotype, a
      desirable agricultural trait. Increased neonatal morbidity is common, however,
      resulting from complications arising from the birth of offspring with increased
      fetal muscle mass. The objective of the current research was to generate an
      attenuated MSTN-null phenotype in a large-animal model using RNA interference to
      enhance muscle development without the detrimental consequences of an
      inactivating mutation. To this end, we identified a series of short interfering
      RNAs that demonstrated effective suppression of MSTN mRNA and protein levels. To
      produce transgenic offspring capable of stable MSTN suppression in vivo, a
      recombinant lentiviral vector expressing a short hairpin RNA (shRNA) targeting
      MSTN for silencing was introduced into bovine fetal fibroblasts. These cells were
      used as nucleus donors for somatic cell nuclear transfer (SCNT). Twenty
      blastocysts were transferred into seven recipient cows resulting in five
      pregnancies. One transgenic calf developed to term, but died following delivery
      by Caesarean-section. As an alternative strategy, microinjection of recombinant
      lentiviral particles into the perivitelline space of in vitro-produced bovine
      zygotes was utilized to produce 40 transgenic blastocysts that were transferred
      into 14 recipient cows, resulting in 7 pregnancies. Five transgenic calves were
      produced, of which three expressed the transgene. This is the first report of
      transgenic livestock produced by direct injection of a recombinant lentivirus,
      and expressing transgenes encoding shRNAs targeting an endogenous gene
      (myostatin) for silencing.

PMID- 22139944
TI  - The evaluation of cascade testing for familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant disorder with a high
      risk of coronary heart disease at a young age that can be reduced by cholesterol
      lowering drugs. Computer simulation was used to estimate the screening
      performance of three strategies of cascade testing for FH (a process of searching
      for relatives with FH once an individual is diagnosed with FH): (i) testing
      parents, siblings, and children (1st degree relatives) of an FH index case, (ii)
      testing (i) and testing 1st degree relatives of subsequently identified relatives
      with FH, and (iii) testing (ii) and also testing aunts, uncles, nephews, nieces,
      grandparents, and first cousins (2nd or 3rd degree relatives) when 1st degree
      relatives of an individual with FH are not available. For cascade testing to
      achieve detection rates of 80%, (i) 25%, (ii) 11%, and (iii) 8% of FH index cases
      who are unrelated need to be identified. To identify these unrelated FH index
      cases, (i) 45% (ii) 23%, and (iii) 17% of all individuals with FH need to be
      identified independently of cascade testing. Cascade testing is not a suitable
      method of population screening for FH, because a separate method of
      systematically identifying new FH index cases is required to achieve a reasonable
      level of FH detection in the population. Such an alternative systematic method of
      identifying new cases could itself be the method of population screening.

PMID- 22139947
TI  - Echocardiography in Saanen-goats: Normal findings, reference intervals in awake
      goats, and the effect of general anesthesia.
AB  - Echocardiographic assessment of cardiac structures, dimensions, and mechanical
      function in goats is poorly documented. The goal of this study was to describe
      normal findings, establish normal values for two-dimensional (2DE) and M-mode
      (MME) echocardiography, and investigate the influence of general anaesthesia.
      Standardized 2DE and MME recordings were obtained on 22 healthy female Saanen
      goats (3.7 +/- 1.1 years [mean +/- SD], 60.2 +/- 10.6 kg) awake (standing) and
      during isoflurane anesthesia (sternal recumbency). Cardiac dimensions and
      function were assessed and compared between treatments (awake vs. anaesthetized).
      Color Doppler imaging and saline contrast studies served to assess abnormal blood
      flow patterns. Post mortem examination was performed in a subset of 12 goats.
      Transthoracic echocardiography was feasible in all goats. Indices of LV systolic
      function proved to be significantly increased during general anesthesia. The
      membranous and occasionally echolucent appearance of the oval fossa suggested
      abnormal interatrial communication in 9 goats. Color Doppler imaging and saline
      contrast studies proved to be inaccurate to detect interatrial shunting of blood.
      Post mortem examination confirmed small persistent foramen ovale in only 3 out of
      7 goats, in which it had been suspected on echocardiography.

PMID- 22139948
TI  - [Objectivity of BSE symptoms using Bayes theorem].
AB  - In clinical epidemiology the Bayes theorem finds ever more use to render clinical
      acting more objective. It is shown that unusual examinations of BSE (bovine
      spongiform encephalopathy) as noise producing with ladle covers may quite
      objectively be evaluated. With the help of the likelihood ratio computed thereby,
      also a ranking of importance (clinical utility) of symptoms can be provided. The
      single most important symptom for BSE is photosensibility.

PMID- 22139949
TI  - [Surgical removing of an ectopic tooth in an Iceland mare].
AB  - Ectopic teeth occur because of failure of the first branchial cleft to close
      during development and are found mostly in young horses. Such dentigerous cysts
      are often located at the base of the ear, forming a notable swelling with a
      fistula, as it was the case with the two year old Iceland mare "Runa". In order
      to confirm the diagnosis, x-ray images were taken, which is also necessary to
      locate the ectopic tooth correctly. While operating, the whole cystic membrane
      should be removed and it is important to prevent adjacent nerves and blood
      vessels from damage. Prognosis for complete healing after removing an ectopic
      tooth is excellent.

PMID- 22139950
TI  - [Feline papillomavirus infection in a cat with Bowen-like disease and cutaneous
      squamous cell carcinoma].
AB  - A cutaneous mass in the neck was excised in a 13-year-old cat. Histopathological
      examination of the resected tissue revealed a multicentric squamous cell
      carcinoma in situ resembling Bowen's disease of man. The tumor showed a
      multifocal transformation to an infiltrative squamous cell carcinoma.
      Histological and immunohistological findings excluded actinic keratosis and
      feline viral plaques and allowed a classification as an irregular non
      hyperkeratotic type of multicentric squamous cell carcinoma in situ. As a
      possible causative agent feline papillomavirus type 2 was detected using nested
      PCR in formalin-fixed material.

PMID- 22139951
TI  - [In Process Citation].

PMID- 22139952
TI  - [In Process Citation].

PMID- 22139954
TI  - [In Process Citation].

PMID- 22139953
TI  - [In Process Citation].

PMID- 22139955
TI  - [In Process Citation].

PMID- 22139956
TI  - Development and validation of a questionnaire evaluating the impact of hepatitis
      B immune globulin prophylaxis on the quality of life of liver transplant
      recipients.
AB  - To date, there is still a lack of instruments for specifically assessing the
      impact of anti-hepatitis B virus prophylaxis after liver transplantation (LT) on
      health-related quality of life (HRQOL) and treatment satisfaction. Focusing on
      the use of hepatitis B immune globulin (HBIG), we developed and validated the
      Immunoglobulin Therapy After Liver Transplantation Questionnaire (ITaLi-Q), which
      includes 41 items and covers 5 domains (side effects, positive and negative
      feelings, impact on the flexibility of daily activities, support, and
      satisfaction). The questionnaire was tested by 177 consecutive LT patients [71.8%
      were male, 38.4% were more than 60 years old, 58.8% were on intramuscular (IM)
      HBIG, and 41.2% were on intravenous (IV) HBIG]. A factor analysis confirmed the
      hypothesized structure, and a multitrait, multi-item analysis showed favorable
      psychometric characteristics for ITaLi-Q: item-scale correlations > 0.40 for all
      items but 1, high scaling success rates (>90% for all scales but 1), excellent
      internal consistency (Cronbach's alpha >= 0.8 for all scales), and good
      reproducibility (test-retest coefficient > 0.70 for all scales but 2). ITaLi-Q
      was able to discriminate between subgroups of patients according to their
      clinical and sociodemographic characteristics. In comparison with patients on IV
      HBIG, patients on IM HBIG reported significantly better HRQOL scores on the
      Flexibility (81.5 +/- 21.4 versus 73.1 +/- 24.2, P = 0.01) and Negative Feelings
      scales (90.1 +/- 17.3 versus 85.4 +/- 20.7, P = 0.04), but they reported worse
      HRQOL scores on the Side Effects scale (81.8 +/- 22.8 versus 95.6 +/- 7.4, P <
      0.001). No differences were found between the route of HBIG administration and
      the Satisfaction, Positive Feelings, Impact, and Support scales. In conclusion,
      ITaLi-Q showed adequate psychometric characteristics and revealed that the route
      of HBIG administration has a significant impact on specific HRQOL domains beyond
      a patient's satisfaction.

PMID- 22139957
TI  - Arterial spin labeling MRI study of age and gender effects on brain perfusion
      hemodynamics.
AB  - Normal aging is associated with diminished brain perfusion measured as cerebral
      blood flow (CBF), but previously it is difficult to accurately measure various
      aspects of perfusion hemodynamics including: bolus arrival times and delays
      through small arterioles, expressed as arterial-arteriole transit time. To study
      hemodynamics in greater detail, volumetric arterial spin labeling MRI with
      variable postlabeling delays was used together with a distributed, dual
      compartment tracer model. The main goal was to determine how CBF and other
      perfusion hemodynamics vary with aging. Twenty cognitive normal female and 15
      male subjects (age: 23-84 years old) were studied at 4 T. Arterial spin labeling
      measurements were performed in the posterior cingulate cortex, precuneus, and
      whole brain gray matter. CBF declined with advancing age (P < 0.001). Separately
      from variations in bolus arrival times, arterial-arteriole transit time increased
      with advancing age (P < 0.01). Finally, women had overall higher CBF values (P <
      0.01) and shorter arterial-arteriole transit time (P < 0.01) than men, regardless
      of age. The findings imply that CBF and blood transit times are compromised in
      aging, and these changes together with differences between genders should be
      taken into account when studying brain perfusion.

PMID- 22139958
TI  - Phenotype-genotype correlations in congenital isolated growth hormone deficiency
      (IGHD).
AB  - Isolated growth hormone deficiency (IGHD) may be congenital, often due to genetic
      mutations, or acquired as a result of other factors such as cranial irradiation.
      The commonest genes implicated in its genetic etiology are those encoding growth
      hormone (GH1) and the receptor for GH-releasing hormone (GHRHR). Rarely, IGHD may
      be caused by mutations in transcription factors (HESX1, SOX3, OTX2) or be the
      first presentation before the development of other pituitary hormone
      deficiencies. IGHD has been classified in four genetic forms (type IA, IB, II and
      III). Despite the increasing number of genes implicated in the etiology of IGHD,
      mutations in known genes account only for a small percentage of cases; therefore,
      other as yet unidentified factors may be implicated in its etiology. Although
      there is no strict genotype/phenotype correlation in patients with IGHD, there
      are some emerging patterns that may guide us towards a genetic diagnosis of the
      condition. There is increasing understanding that the phenotype of patients with
      IGHD is highly variable and sometimes even evolving, dictating the need for long
      term follow-up in these cases.

PMID- 22139959
TI  - Vitamins, minerals, essential fatty acids and colorectal cancer risk in the
      United Kingdom Dietary Cohort Consortium.
AB  - The risk for colorectal cancer may be influenced by the dietary intake of various
      vitamins, minerals and essential fatty acids. We conducted a pooled analysis of
      dietary data collected using food diaries in seven prospective studies in the
      United Kingdom Dietary Cohort Consortium. Five hundred sixty-five cases of
      colorectal cancer were matched with 1,951 controls on study centre, age, sex and
      recruitment date. Dietary intakes of retinol, vitamin A, thiamin, riboflavin,
      vitamin B6, folate, vitamin B12, vitamin D, calcium, iron, magnesium, potassium,
      n - 6 fatty acids, n - 3 fatty acids and the ratio of n - 6 to n - 3 fatty acids
      were estimated and their associations with colorectal cancer examined using
      conditional logistic regression models, adjusting for exact age, height, weight,
      energy intake, alcohol intake, fiber intake, smoking, education, social class and
      physical activity. There were no statistically significant associations between
      colorectal cancer risk and dietary intake of any of the vitamins, minerals or
      essential fatty acids examined.

PMID- 22139961
TI  - Relative efficacy of steroid therapy in immune thrombocytopenia mediated by anti
      platelet GPIIbIIIa versus GPIbalpha antibodies.
AB  - Immune thrombocytopenia (ITP) is characterized by platelet clearance mediated
      primarily by autoantibodies against the platelet GPIIbIIIa and/or GPIbalpha.
      Steroid therapy is a first-line treatment for ITP. However, some patients are
      refractory to this therapy and currently no method can predict which patients
      will respond. To evaluate whether steroids are equally efficacious in treating
      patients with ITP caused by anti-GPIIbIIIa versus anti-GPIbalpha antibodies, we
      performed a retrospective study on 176 newly diagnosed patients with acute ITP
      who had severe bleeding symptoms and were admitted as resident patients to the
      hospital. The patients were treated first with intravenous administration of high
      dose dexamethasone (DXM), followed by oral administration of prednisone. Response
      to therapy was observed in a majority of patients with antibodies specific for
      GPIIbIIIa (31/43) or without detectable antibodies against either GPIIbIIIa or
      GPIbalpha (36/45). In contrast, the steroid response was significantly lower in
      patients with anti-GPIbalpha antibodies (9/34) or with antibodies against both
      GPIbalpha and GPIIbIIIa (16/54). The preliminary findings of this study suggest
      that in future prospective clinical trials including corticosteroids, the anti
      GPIbalpha, and -GPIIbIIIa status should be assessed in order to test its
      potential relevance in deciding future treatments.

PMID- 22139963
TI  - Differential expression of cyclophilin A and EMMPRIN in developing molars of
      rats.
AB  - A complex and intricate cascade of gene expression is essential for late stage
      tooth development. This study was performed to detect molecules involved in
      dental hard tissue formation and tooth eruption by comparing gene expression in
      cap stage molar germs (before eruptive movement and dental hard tissue formation)
      with that in root formation stage molar germs (after eruptive movement and dental
      hard tissue formation). DD-PCR revealed that cyclophilin A (Cyp-A), a potent
      chemoattractant for monocytes as well as a ligand for extracellular matrix
      metalloproteinase inducer (EMMPRIN) was expressed differentially in the two
      stages molar germs. The levels of Cyp-A and EMMPRIN mRNA were significantly
      higher at the root formation stage than at the cap and crown stages of the molar
      germs. Immunofluorescence showed that Cyp-A and EMMPRIN were expressed strongly
      in the follicular cells overlaying the occlusal region of the molar germs at the
      root formation stage. In contrast, their immunoreactivity was weak in the
      follicular tissues and was not region-specific in molar germs at the cap stage.
      In addition, the MCP-1 and CSF-1 mRNA levels increased in parallel to that of Cyp
      A mRNA and the increased number of osteoclasts at the occlusal region.
      Immunoreactivity against Cyp-A and EMMPRIN was also observed in the fully
      differentiated ameloblasts and odontoblasts. This study suggests that Cyp-A and
      EMMPRIN play roles in the maturation of dental hard tissue and the formation of
      an eruption pathway.

PMID- 22139962
TI  - The epigenome in early vertebrate development.
AB  - Epigenetic regulation defines the commitment and potential of cells, including
      the limitations in their competence to respond to inducing signals. This review
      discusses the developmental origins of chromatin state in Xenopus and other
      vertebrate species and provides an overview of its use in genome annotation. In
      most metazoans the embryonic genome is transcriptionally quiescent after
      fertilization. This involves nucleosome-dense chromatin, repressors and a
      temporal deficiency in the transcription machinery. Active histone modifications
      such as H3K4me3 appear in pluripotent blastula embryos, whereas repressive marks
      such as H3K27me3 show a major increase in enrichment during late blastula and
      gastrula stages. The H3K27me3 modification set by Polycomb restricts ectopic
      lineage-specific gene expression. Pluripotent chromatin in Xenopus embryos is
      relatively unconstrained, whereas the pluripotent cell lineage in mammalian
      embryos harbors a more enforced type of pluripotent chromatin.

PMID- 22139964
TI  - A simple and successful sonographic technique to identify the sciatic nerve in
      the parasacral area.
AB  - BACKGROUND: The purpose of this study was to describe detailed sonographic
      anatomy of the parasacral area for rapid and successful identification of the
      sciatic nerve. METHODS: Fifty patients scheduled for knee surgery were included
      in this observational study. An ultrasound-guided parasacral sciatic nerve block
      was performed in all patients. The ultrasound probe was placed on an axial plane
      8 cm lateral to the uppermost point of the gluteal cleft. Usually, at this level
      the posterior border of the ischium (PBI), a characteristically curved
      hyperechoic line, could be identified. The sciatic nerve appeared as a
      hyperechoic structure just medial to the PBI. The nerve lies deep to the
      piriformis muscle lateral to the inferior gluteal vessels, and if followed
      caudally, it rests directly on the back of the ischium. After confirmation with
      electrical stimulation, a 20-mL mixture of 1% ropivacaine and 1% lidocaine with
      epinephrine was injected. RESULTS: The sciatic nerve was identified successfully
      in 48 patients (96%). In those patients, the median time required for its
      ultrasonographic identification was ten seconds [interquartile range, 8-13.7
      sec], and the block success rate was 100%. CONCLUSION: The described sonographic
      details of the parasacral area allowed for rapid and successful identification of
      the sciatic nerve.

PMID- 22139965
TI  - Review article: assessment in anesthesiology education.
AB  - PURPOSE: The purpose of this article is to provide a review of the competencies
      and associated assessment techniques relevant to the practice of anesthesiology.
      Although many of the competencies are difficult to define and measure
      specifically, advances in assessment techniques have provided more opportunities
      to gather meaningful performance data. PRINCIPAL FINDINGS: Establishing the
      competence of anesthesiologists demands a host of measures, including
      standardized tests and less-structured peer evaluations. Simulation-based
      assessment will play an increasingly important role both in certification and in
      maintenance of certification for anesthesiologists. CONCLUSIONS: While there are
      many psychometric challenges associated with the assessments pertinent to the
      education of anesthesiologists, technological advances combined with an increased
      awareness of sound measurement principles will yield more meaningful competency
      measures that can be used to improve the practice of anesthesiology.

PMID- 22139966
TI  - Cessation of vascular endothelial growth factor-targeted therapy in patients with
      metastatic renal cell carcinoma: feasibility and clinical outcome.
AB  - BACKGROUND: The current treatment of metastatic renal cell carcinoma (mRCC) with
      vascular endothelial growth factor (VEGF)-targeted agents is continuous therapy
      until progression of disease (PD) or unacceptable toxicity. Chronic mild to
      moderate toxicity and risk of long-term toxicity ensue for some patients. It is
      hypothesized that patients with an initial response to treatment can maintain
      disease control off all therapy for a period of time. METHODS: A retrospective
      study of patients with mRCC who initiated VEGF-targeted therapy between January
      2004 and December 2009 at The Cleveland Clinic Foundation, Cleveland, Ohio, or
      Institut Gustave-Roussy, Villejuif, France, was conducted. Patients had achieved
      RECIST (Response Evaluation Criteria in Solid Tumors)-defined stable disease or
      better on therapy, and were then taken off all therapy for reasons not including
      disease progression. Patient, disease, and therapy characteristics were recorded.
      The primary objective was progression-free survival (PFS), measured as the time
      from discontinuation of therapy to RECIST-defined PD. RESULTS: Forty patients
      were identified. After a median follow-up of 29.7 months (range, 4.2 to 84.7
      months), 25 patients (63%) had PD off therapy (median PFS, 10.0 months; range,
      1.4-27.2 months). Among these patients, 8 (32%) had progression in sites that
      were not previously involved with disease. Heng risk group (hazard ratio, 2.49;
      95% confidence interval, 1.19-5.22; P = .011) and achievement of a complete
      response prior to discontinuing therapy (hazard ratio, 0.20; 95% confidence
      interval, 0.04-0.86; P = .025) were independent predictors of PFS in a
      multivariable Cox proportional hazards model. CONCLUSIONS: A select subset of
      mRCC patients achieving stable disease or better on VEGF-targeted therapy can be
      observed off all therapy. Further prospective investigation is warranted.

PMID- 22139968
TI  - Absence of COCH gene mutations in patients with superior semicircular canal
      dehiscence.

PMID- 22139969
TI  - Testing the Short and Screener versions of the Social Adjustment Scale-Self
      report (SAS-SR).
AB  - The 54-item Social Adjustment Scale-Self-report (SAS-SR) is a measure of social
      functioning used in research studies and clinical practice. Two shortened
      versions were recently developed: the 24-item SAS-SR: Short and the 14-item SAS
      SR: Screener. We briefly describe the development of the shortened scales and
      then assess their reliability and validity in comparison to the full SAS-SR in
      new analyses from two separate samples of convenience from a family study and
      from a primary care clinic. Compared to the full SAS-SR, the shortened scales
      performed well, exhibiting high correlations with full SAS-SR scores (r values
      between 0.81 and 0.95); significant correlations with health-related quality of
      life as measured by the Short Form 36 Health Survey; the ability to distinguish
      subjects with major depression versus other psychiatric disorders versus no
      mental disorders; and sensitivity to change in clinical status as measured
      longitudinally with the Symptom Checklist-90 and Global Assessment Scale. The SAS
      SR: Short and SAS-SR: Screener retained the areas assessed by the full SAS-SR
      with fewer items in each area, and appear to be promising replacements for the
      full scale when a shorter administration time is desired and detailed information
      on performance in different areas is not required. Further work is needed to test
      the validity of the shortened measures.

PMID- 22139970
TI  - A self-assembled complex with a titanium(IV) catecholate core as a potential
      bimodal contrast agent.
AB  - A ditopic chelating ligand (H(6)4) that bears catechol and diethylenetriamine
      N,N,N',N'',N''-pentaacetate (DTPA) has been designed and shown to specifically
      bind lanthanide(III) ions at the DTPA core ([Ln(H(2)4)(H(2)O)](-)) and further
      self-assemble with titanium(IV), thereby giving rise to the formation of a
      supramolecular metallostar complex with a lanthanide(III)-to-titanium(IV) ratio
      of 3:1, [(Ln4)(3)Ti(H(2)O)(3)](5-) (Ln=La, Eu, Gd). The efficacy of the
      metallostar complex as a potential bimodal optical/magnetic resonance imaging
      (MRI) agent has been evaluated. Nuclear magnetic relaxation dispersion (NMRD)
      measurements for the [(Gd4)(3)Ti(H(2)O)(3)](5-) complex have demonstrated an
      enhanced r(1) relaxivity that corresponds to 36.9 s(-1) mM(-1) per metallostar
      molecule at 20 MHz and 310 K, which is a result of a decreased tumbling rate. The
      ability of the complex to bind to human serum albumin (HSA) was also examined by
      relaxometric measurements. In addition, upon UV irradiation the
      [(Gd4)(3)Ti(H(2)O)(3)](5-) complex exhibits broad-band green emission in the
      range 400-750 nm with a maximum at 490 nm. Taking into account the high
      relaxivity and luminescence properties, the [(Gd4)(3)Ti(H(2)O)(3)](5-) complex is
      a good lead compound for the development of efficient bimodal contrast agents.

PMID- 22139971
TI  - Vascular endothelial growth factor (VEGF) gene polymorphisms may influence the
      efficacy of thalidomide in multiple myeloma.
AB  - Vascular endothelial growth factor (VEGF) is a potent proangiogenic factor.
      Several single nucleotide polymorphisms (SNPs) in the VEGF gene with influence on
      VEGF expression have been described. In multiple myeloma, VEGF stimulates
      angiogenesis which is correlated with disease progression and prognosis. In this
      study, we evaluated the association between genetic variations in the VEGF gene
      in patients with multiple myeloma and time to treatment failure (TTF) after high
      dose melphalan and stem cell support (HDT), overall survival (OS) and efficacy of
      the anti-angiogenic drug thalidomide. Retrospectively, the SNPs -2,578C>A
      (rs699947), -460C>T (rs833061), +405G>C (rs2010963) and +936C>T (rs3025039) in
      the VEGF gene were examined in 348 patients with newly diagnosed multiple myeloma
      initially treated with HDT, where 176 patients were treated with thalidomide at
      relapse. None of the examined geno- or haplotypes was associated with differences
      in TTF after initial therapy or OS. A possible relation between the haplotype 
      2,578A/-460C/+405G (ACG) and effect of thalidomide was seen. Patients with no
      copies of the haplotype ACG had a longer time to next treatment than patients
      with one or two copies of the haplotype ACG, median 13.7 months vs. 9.2 months,
      p=0.007. In conclusion, the haplotype ACG in the VEGF gene may influence the
      efficacy of thalidomide in multiple myeloma. Further analyses are needed to
      confirm these findings and get insight into the functional effect of these
      polymorphisms, so in the future we may be able to select multiple myeloma
      patients who especially will benefit from treatment with thalidomide.

PMID- 22139972
TI  - Implications of a positive crossmatch in liver transplantation: a 20-year review.
AB  - Whether a positive crossmatch result has any relevance to liver transplantation
      (LT) outcomes remains controversial. We assessed the impact of a positive
      crossmatch result on patient and graft survival and posttransplant complications.
      During a 20-year period, 2723 LT procedures with crossmatch results were
      identified: 2479 primary transplants and 244 retransplants. The rates of positive
      B cell and T cell crossmatches were 10.1% and 7.4%, respectively, for primary
      transplants and 14.6% and 6.4%, respectively, for retransplants (P = 0.049 for a
      B cell crossmatch). Across all primary transplants, females (P < 0.001) and
      patients with autoimmune hepatitis (P < 0.001) had greater frequencies of
      positive crossmatches. There was no effect from race or age. For both primary
      transplants and retransplants, patient survival and graft survival were not
      affected by the presence of a positive crossmatch. With respect to posttransplant
      complications, there were no differences in rejection episodes (hyperacute,
      acute, or chronic) or technical complications (biliary and vascular) between
      negative and positive crossmatch groups. However, there were significant
      differences in the pathological findings of preservation injury (PI) on liver
      biopsy samples taken at the time of transplantation and within the first week of
      transplantation (P = 0.003 for B cells and P = 0.03 for T cells). In summary, a
      positive crossmatch had no significant impact on patient survival or graft
      outcomes. However, there was a significantly higher incidence of PI in primary LT
      recipients with a positive crossmatch. This finding is important for a broader
      understanding of PI, which may include a significant immunological component.

PMID- 22139973
TI  - A novel assay for quantifying the number of plasmids encapsulated by polymer
      nanoparticles.

PMID- 22139974
TI  - Diffusion-prepared fast imaging with steady-state free precession (DP-FISP): a
      rapid diffusion MRI technique at 7 T.
AB  - Diffusion MRI is a useful imaging technique with many clinical applications. Many
      diffusion MRI studies have utilized echo-planar imaging (EPI) acquisition
      techniques. In this study, we have developed a rapid diffusion-prepared fast
      imaging with steady-state free precession MRI acquisition for a preclinical 7T
      scanner providing diffusion-weighted images in less than 500 ms and diffusion
      tensor imaging assessments in ~1 min with minimal image artifacts in comparison
      with EPI. Phantom apparent diffusion coefficient (ADC) and fractional anisotropy
      (FA) assessments obtained from the diffusion-prepared fast imaging with steady
      state free precession (DP-FISP) acquisition resulted in good agreement with EPI
      and spin echo diffusion methods. The mean apparent diffusion coefficient was 2.0
      * 10(-3) mm(2) /s, 1.90 * 10(-3) mm(2) /s, and 1.97 * 10(-3) mm(2) /s for DP
      FISP, diffusion-weighted spin echo, and diffusion-weighted EPI, respectively. The
      mean fractional anisotropy was 0.073, 0.072, and 0.070 for diffusion-prepared
      fast imaging with steady-state free precession, diffusion-weighted spin echo, and
      diffusion-weighted EPI, respectively. Initial in vivo studies show reasonable ADC
      values in a normal mouse brain and polycystic rat kidneys.

PMID- 22139976
TI  - Regional differences in grey and white matter in children and adults with autism
      spectrum disorders: an activation likelihood estimate (ALE) meta-analysis.
AB  - Structural alterations in brain morphology have been inconsistently reported in
      children compared to adults with autism spectrum disorder (ASD). We assessed
      these differences by performing meta-analysis on the data from 19 voxel-based
      morphometry studies. Common findings across the age groups were grey matter
      reduction in left putamen and medial prefrontal cortex (mPFC) and grey matter
      increases in the lateral PFC, while white matter decreases were seen mainly in
      the children in frontostriatal pathways. In the ASD sample, children/adolescents
      were more likely than adults to have increased grey matter in bilateral fusiform
      gyrus, right cingulate and insula. Results show that clear maturational
      differences exist in social cognition and limbic processing regions only in
      children/adolescents and not in adults with ASD, and may underlie the emotional
      regulation that improves with age in this population.

PMID- 22139975
TI  - Rational bioprocess design for human pluripotent stem cell expansion and endoderm
      differentiation based on cellular dynamics.
AB  - We present a predictive bioprocess design strategy employing cell- and molecular
      level analysis of rate-limiting steps in human pluripotent stem cell (hPSC)
      expansion and differentiation, and apply it to produce definitive endoderm (DE)
      progenitors using a scalable directed-differentiation technology. We define a
      bioprocess optimization parameter (L; targeted cell Loss) and, with quantitative
      cell division tracking and fate monitoring, identify and overcome key suspension
      bioprocess bottlenecks. Adapting process operating conditions to pivotal
      parameters (single cell survival and growth rate) in a cell-line-specific manner
      enabled adherent-equivalent expansion of hPSCs in feeder- and matrix-free defined
      medium suspension culture. Predominantly instructive differentiation mechanisms
      were found to underlie a subsequent 18-fold expansion, during directed
      differentiation, to high-purity DE competent for further commitment along
      pancreatic and hepatic lineages. This study demonstrates that iPSC expansion and
      differentiation conditions can be prospectively specified to guide the enhanced
      production of target cells in a scale-free directed differentiation system.

PMID- 22139977
TI  - Generation of mice with conditional null allele for GdX/Ubl4A.
AB  - GdX (also named Ubl4A) is a house-keeping gene located on the X chromosome and
      encodes a protein harboring an ubiquitin-like domain in human and mouse. Although
      identified in 1988, the function of GdX remains unknown. To elucidate the role of
      GdX in vivo, we generated a conditional GdX knockout mouse in which Exon 2 was
      flanked by two loxP sites. We obtained viable and fertile mice with homozygous
      GdX(flox/flox) or GdX(flox/Y) allele. Germ-line transmission was confirmed by
      crossing the mouse bearing conditionally targeted allele with an EIIalpha-Cre
      transgenic mouse. GdX was successfully depleted in tissues of EIIalpha-Cre-GdX
      null mice. GdX(-/-) and GdX(-/Y) mice are viable and exhibit normal development
      compared with wild-type littermates within 6 months during our observation. We
      also observed that GdX knockout male mice were functionally normal in the
      reproductive system where Ubl4B was specifically expressed. GdX(flox/flox) and
      GdX(flox/Y) conditional mice provide a tool for further tissue-specific function
      analysis of the GdX protein under different conditions.

PMID- 22139978
TI  - Association between gastric mucosal glutathione-S-transferase activity,
      glutathione-S-transferase gene polymorphisms and Helicobacter pylori infection in
      gastric cancer.
AB  - AIM: Helicobacter pylori infection, though common, leads to gastric cancer (GC)
      in less than 1% individuals, suggesting the role of host factors. We previously
      reported the role of glutathione-S-transferase (GST) polymorphisms, the gene
      encoding a carcinogen-detoxifying enzyme, in GC. This study was aimed to evaluate
      GST enzyme activity, GST polymorphism, glutathione (GSH) levels and H. pylori in
      patients with GC. METHODS: GST and GSH levels were estimated in gastric biopsies
      of 52 patients with GC, 37 functional dyspepsia (FD) and 39 peptic ulcer (PU),
      and correlated with H. pylori (ELISA) infection and GST polymorphisms. GST
      polymorphisms were separately analyzed in relationship to H. pylori in 82 GC, 72
      FD, 53 PU and 89 healthy controls (HC). RESULTS: GST activity was lower in
      patients with GC in comparison to PU (p = 0.03), but GSH levels were comparable.
      GSTT1 null genotype (GSTT1*0) and simultaneous deletion of both GSTT1 and GSTM1
      genes was associated with lower enzyme activity (p = 0.02 and 0.01,
      respectively). GST and GSH levels in H. pylori positive and negative patients
      with GC, FD and PU were comparable. Presence of H. pylori infection along with
      GSTT1*0 (p = 0.006) and GSTM1*0 (p = 0.05) was associated with lower enzyme
      activity. GSTT1*0 was associated with higher odds ratio (OR) of GC in presence of
      H. pylori (GC vs. HC: p = 0.02, OR 2.6 [95% CI = 1-6] vs. p = 0.7, 1.3 [0.4-5.0];
      GC vs. PU: p = 0.04, OR 3 [95% CI = 1-9] vs. not applicable (OR could not be
      computed as frequency of GSTT1*0 in H. pylori negative patients with PU was
      zero)]. CONCLUSIONS: GC is associated with reduced GST activity. Odds ratio of GC
      associated with GSTT1*0 is enhanced in presence of H. pylori probably due to
      combined effect of both on enzyme activity.

PMID- 22139979
TI  - Practical approach for characterization of glucose 6-phosphate dehydrogenase
      (G6PD) deficiency in countries with population ethnically heterogeneous:
      description of seven new G6PD mutants.
AB  - We present a rapid strategy based on Restriction Fragment Length Polymorphism
      (RFLP) analysis to characterize the more frequent glucose 6-phosphate
      dehydrogenase (G6PD) variants observed in a population with high gene flow.
      During a study involving more than 600 patients, we observed mainly G6PD A(-)
      (c.202G>A, c.376A>G; p.Val68Met, p.Asn126Asp), G6PD Mediterranean (Med)
      (c.563C>T, p.Ser188Phe), and G6PD Betica (c.376A>G, 542A>T; p.126Asn>Asp,
      181Asp>Val) with addition of a few rare ones. A number of 10 abnormalities
      amounted to 92% of all the molecular defects. In addition, seven new mutations
      were found: three presented with acute hemolytic anemia following oxidative
      stress [G6PD Nice (c.1380G>C, p.Glu460Asp), G6PD Roubaix (c.811G>C, p.Val271Leu),
      and G6PD Toledo (c.496C>T, p.Arg166Cys)], three with different degrees of chronic
      hemolytic anemia [G6PD Lille (c.821A>T, p.Glu274Val), G6PD Villeurbanne
      (c.1000_1002delACC, p.Thr334del), and G6PD Amiens (c.1367A>T, p.Asp456Val)] and
      one found fortuitously G6PD Montpellier (c.1132G>A, p.Gly378Ser).

PMID- 22139980
TI  - Jacobsen syndrome due to an unbalanced translocation between 11q23 and 22q11.2
      identified at age 40 years.
AB  - A woman with psychomotor developmental delay, congenital glaucoma, and
      distinctive facial features, and a short neck was diagnosed with Jacobsen
      syndrome (JBS) at age 40 years. A previously reported balanced translocation
      between chromosome 11 and 22 instead showed an unbalanced translocation by a
      microarray-based comparative hybridization analysis with the final karyotype of
      46,XX,der(11)t(11;22)(q23.3;q11.21),del(22)(q11.21) dn. The breakpoint of
      chromosome 11 was determined to be at TECTA and not near the apolipoprotein gene
      cluster site or the fragile site (FRA11B), which are commonly seen in patients
      with t(11;22) and patients with typical 11q deletions, respectively. Although the
      phenotypic features of the patient, including psychomotor developmental delay,
      distinctive features, and mild thrombocytopenia, were consistent with JBS,
      congenital glaucoma, which is an uncommon finding of JBS, was the most prominent
      condition during her natural history.

PMID- 22139981
TI  - [What does the practicing doctor need to know about the transplantation law and
      its effects?].
AB  - The present article will give a related overview of the current background of the
      field of donor recruitment and transplantation medicine. The transplantation Law
      that came into effect on the 01.07.2007 has caused numerous changes in the
      identification and reporting of potential organ- and tissue donors in hospitals
      with accredited Intensive care units. The law has had a great influence on the
      allocation practice of the rare organs in Switzerland. With just 12.6 cadaveric
      donors per million inhabitants, Switzerland is, compared to other European
      countries at the bottom of the table. This is not without influence on the
      waiting list, which at the end of 2010 was at a new all time high with 1029
      patients.  We assume that almost half of the Swiss population has not yet decided
      if they want to donate their organs or not. The most important contact people in
      this subject are the practicing colleagues, by this we mean you. On a specially
      publicized Link [www.swisstransplant.org/medizinerinfo] you will find more
      information and documents that you can either put out in your practice or
      download them for further education. Organ donation is possible until a high age,
      bring this subject up with your patients, and inform them transparently and
      openly about this. Ask your patients to inform their loved ones of their decision
      for or against organ donation.

PMID- 22139982
TI  - [Immunosuppressive drugs - how they work, their side effects and interactions].
AB  - The central issue in organ transplantation remains suppression of allograft
      rejection. Immunosuppression can be achieved by depleting lymphocytes, diverting
      lymphocyte traffic, or blocking lymphocyte response pathways. Immunosuppressive
      drugs include small-molecule drugs, depleting and nondepleting protein drugs
      (polyclonal and monoclonal antibodies), fusion proteins, intravenous immune
      globulin, and glucocorticoids. Small-molecule immunosuppressive agents include
      calcineurin-inhibitors (cyclosporine, tacrolimus), Target-of-Rapamycin Inhibitors
      (Sirolimus, Everolimus), inhibitors of nucleotide synthesis and azathioprine. The
      review covers the mode of action of these drugs with a special focus on
      belatacept, a new promising fusion protein. Different immuo-suppressive
      strategies mean also different safety profiles. Common side effects include the
      consequences of diminished immuno- response, i.e. infections and cancer (mainly
      involving the skin). Toxic side effects of immunosuppressive drugs range in a
      wide spectrum that involves almost every organ. The major interest of this toxic
      effects is the cardiovascular tolerance (with large differences from drug to
      drug), that are discussed seperately. The calcineurin- and mTOR-inhibitors are
      both metabolized by the CYP450 3A4 enzyme, which is also involved in the
      metabolism of many other drugs. The review discusses the most important
      interactions that in- or decreases the through level of these drugs.

PMID- 22139983
TI  - [Renal transplantation - new developments].
AB  - Renal transplantation has become an established option for renal replacement
      therapy in many patients with end stage renal disease. Living donation is a
      possibility for timely transplantation, hampered in 20 % of all possible donors
      and recipients byincompatible blood groups. AB0-incompatible renal
      transplantation overcomes this hurdle with acceptable allograft survival compared
      to conventional living-donor renal transplantation. During the last 10 years, the
      number of patients awaiting renal transplantation older than 65 years has nearly
      doubled. The decision to transplant those patients and their medical treatment is
      a growing challenge in transplantation. On the other hand donor age is increasing
      with potential negative consequences for long-term outcome of organ function.
      Antibody-mediated humoral rejection have been identified lately as an important
      cause for allograft failure during long-term follow up of renal transplant
      patients. New immunological methods to detect donor-specific antibodies, like
      solid-phase assays (Luminex(r)), have increased the knowledge and understanding
      of humoral rejection processes. This will lead hopefully to modified
      immunosuppressive strategies to minimize organ failure due to chronic rejection.

PMID- 22139984
TI  - [The risk of living kidney donation].
AB  - Living kidney donation was started in the seventies in Switzerland and since the
      year 2000 all transplant centers in Switzerland perform this procedure. It shows
      excellent long-term results in terms of graft and patient survival with an
      acceptable risk for the donor. Due to the shortage of deceased kidney donors
      available for transplantation and the rising number of patients on the waiting
      list, there is an increasing pressure towards living kidney donation reflected by
      the rise of living-donor kidney transplantation since the last decade. Due to
      this pressure it is important to do a very careful medical and psychological
      evaluation. In addition it is important to inform the donors about the possible
      risks of kidney donation which includes the short as well as the long term
      prognosis. This is only possible with a prospective long-term analysis of all
      living donor in specific country. In Switzerland this is guaranteed by the Swiss
      Organ Living Donor Health Registry (SOL-DHR), which is world wide the only
      prospective national donor registry with an actual follow up of 18 years. The
      following manuscript summarizes the medical and psychological evaluations of
      living kidney donors and delivers insight in the risks and the possible long-term
      effects of living kidney donation.

PMID- 22139985
TI  - [End-stage nephropathy in type 1-diabetes mellitus - kidney transplantation alone
      or combined with islet or pancreas transplantation?].
AB  - Due to the recent changes in reimbursement politics in islet and pancreas
      transplantation in Switzerland, the question, which patients with type 1-diabetes
      mellitus get which form of beta-cell replacement, is of utmost importance for
      referring physicians. As of July 1, 2010 all forms of islet- or pancreas
      transplantations are reimbursed by the Swiss health care system. The limited
      availability of donor organs and the necessity of transplantation of the islets
      of several pancreata in order to achieve insulin independence has led to a change
      in paradigms in Switzerland, where insulin independence by multiple islet
      transplantations is not the key goal in islet transplantation any longer. The
      primary goal is achieving a good blood glucose control and avoidance of severe
      hypoglycaemic episodes. This goal can be achieved in 80 - 90 % of all patients.
      Only if this goal cannot be achieved by a single islet transplantation, a second
      or third islet transplantation is performed. By adapting this strategy more
      patients can benefit from this new therapy. Unlike the North American centers,
      the Swiss centers in Zurich and Geneva concentrated their efforts on islet after
      kidney and simultaneous islet kidney transplantation. Due to the organ donor
      shortage in Switzerland, 50 % of kidney transplants are nowadays living-organ
      donations, therefore this option has to be included in the decision tree of a
      beta cell replacement. The choice between islet and pancreas transplantation
      depends on the existence of diabetes complications (because the perioperative
      risk is considerably higher in pancreas transplantation) and the potential
      benefit of a pancreas- or islet transplantation. The first question in the
      decision tree is, therefore, whether the patient with type 1-diabetes and severe
      renal failure is a potential candidate for simultaneous pancreas-islet
      transplantation. If the perioperative risk is considered to be too high, or if
      revascularisation procedures cannot be done before transplantation, the patient
      qualifies only for islet transplantation. If a living organ donation for the
      kidney is possible and the patient not yet on dialysis then the patient can be
      listed for simultaneous islet-kidney or pancreas-kidney-transplantation. If
      dialysis is imminent or already performed, a living-donor kidney should be
      transplanted with the option of a later islet- or pancreas after kidney
      transplantation. If the patient with type 1-diabetes mellitus is able to maintain
      a reasonable glycemic level, he would be a good candidate for islet
      transplantation. If the patient is willing to take the additional risk of
      complications associated with a pancreas transplant, was never able to maintain a
      good glycated haemoglobin, has an acceptable perioperative risk, and wishes to
      become insulin-independent, a simultaneous pancreas-kidney transplant would be
      recommended. If the kidney has already been transplanted previously, a pancreas-
      after kidney transplantation would be the procedure of choice. An islet or
      pancreas transplantation alone is reserved for the patient with type 1-diabetes
      with a good renal function and frequent life-threatening hypoglycemias, which
      have to be balanced against the risks of a life-long immunosuppression. In this
      review article the advantages, disadvantages, and current indications for both
      beta-cell replacement options in Switzerland are discussed in the light of the
      available evidence with the help of a new flow chart.

PMID- 22139986
TI  - [Liver transplantation - when and for whom it should be performed].
AB  - During the past two decades, orthotopic liver transplantation (OLT) emerged to
      the treatment of choice for patients with end-stage liver disease. In
      Switzerland, about 100 liver transplantations are performed every year, while the
      shortage of cadaveric organs considerably outmatches the demand. Common
      indications for OLT include cirrhosis due to alcoholic liver disease or chronic
      viral hepatitis related to hepatitis B or C, and hepatocellular carcinoma. With
      the advent of the new allocation policy in Switzerland in 2007, patients listed
      for OLT are mainly stratified based on the Model of End-stage Liver Disease
      (MELD) score. Using a patient's laboratory values for serum bilirubin, serum
      creatinin, and the international normalized ratio for prothrombin time (INR), the
      MELD score accurately predicts three-month mortality among patients on the
      waiting list. Compared to the pre-MELD era, patients with significantly higher
      MELD scores undergo transplantation which leads in turn to more complications and
      higher costs yet with a comparable outcome. Timely referral of potential
      candidates to a transplant center is crucial since thorough evaluation to rule
      out contraindications such as uncontrolled infection, extrahepatic malignancy or
      advanced cardiopulmonary disease is essential. Taken together, every patient
      presenting with acute liver failure, decompensated cirrhosis or suspected
      hepatocellular carcinoma should be evaluated in a center with liver
      transplantation capability.

PMID- 22139987
TI  - [Advanced heart failure - treatment options beyond medical management].
AB  - Improvement of heart failure therapy has led to a far better survival and quality
      of life of patients. Treatment of the underlying disease, patient education and
      improvement of compliance and consequent upgrading of medical heart failure
      therapy often delays further progression to an advanced stage of heart failure.
      Nevertheless heart failure remains a chronic progressive disease and it is up to
      the treating clinician to identify the signs of advanced heart failure in a
      timely manner in order to evaluate patients for further treatment strategies such
      as heart transplantation. This article should help define advanced heart failure
      and illustrate how patients are evaluated for further therapy. Outcome of heart
      transplantation or mechanically assisted circulatory support is strongly
      associated to proper patient selection and timing.

PMID- 22139988
TI  - [Lung transplantation and patient evaluation].
AB  - To date, lung transplantation is an established therapeutic modality for advanced
      lung disease. Post-transplant survival is excellent, but depends on sophisticated
      medical follow-up and treatment by a dedicated and experienced multidisciplinary
      lung transplant team. Transplantation leads to markedly improved quality of life.
      Medical complications after lung transplantation are frequent, such as infections
      (viral, bacterial and fungal), gastro-esophageal reflux, osteoporosis and chronic
      rejection. Prevention of these complications is crucial and lifelong adherence to
      therapy is warranted. The most important hurdle in transplantation medicine to
      date is the marked shortage of donor organs making it impossible to transplant
      all patients in need. Living donation and ex vivo reconditioning of marginal
      lungs might bring some relief.

PMID- 22139989
TI  - [Hand transplantation - fiction or reality?].
AB  - Hand transplantation has been indicated in selective patients after traumatic
      upper extremity amputation and only performed in a few centers around the world
      for the last decade. In comparison to solid organ transplantation, there is a
      challenge to overcome the host immunological barrier due to complex antigenicity
      of the different included tissues, the skin being the most susceptible to
      rejection. Patients require lifelong immunosuppression for non life-threatening
      conditions. Minimization of maintenance immunosuppression represents the key step
      for promoting wider applicability of hand transplantation. Current research is
      working towards the understanding mechanisms of composite tissue allograft (CTA)
      rejection. Worldwide, in 51 patients 72 hands (21 double hand transplants) and
      once both arms have been successfully transplanted since 1998.

PMID- 22139990
TI  - [Infections in solid organ transplantation - prophylaxis, diagnostic approach and
      therapy].
AB  - Organ transplant candidates should be optimally screened before transplantation
      and latent and chronic infections treated. Vaccination status should be reviewed
      to ensure full compliance with the recommended vaccinations schedule. After
      transplantation, immunosuppressive therapy increases the risk for infectious
      complications. An aggressive diagnostic approach is mandatory and must weigh the
      time elapsed after transplantation as well as the net state of immunosuppression.
      Principles of establishing a differential diagnosis in transplanted individuals
      suspected of having an infectious complication are presented. Furthermore, common
      opportunistic infections and current prevention strategies are discussed.

PMID- 22139991
TI  - Spontaneous adverse event reports of Stevens-Johnson syndrome/toxic epidermal
      necrolysis: detecting associations with medications.
AB  - PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are
      medically serious skin reactions that are often drug induced. The mainstay of
      therapy and future prevention is to discontinue and avoid the use of the
      suspected inducing drug. However, many cases of SJS/TEN occur in patients who are
      taking multiple medications, and it is often difficult to determine which drug to
      stop. This analysis was conducted to identify drugs that were most associated
      with SJS/TEN in the US Food and Drug Administration (FDA) Adverse Event Reporting
      System (AERS) database and to identify medications that were likely innocent
      bystanders. METHODS: A Multi-item Gamma Poisson Shrinker value with an EB05 >= 2
      was considered a disproportional increase in reporting frequency (at least two
      times higher than expected). The identified drugs with reporting frequency of
      SJS/TEN in the US FDA AERS database were then compared to the EuroSCAR (European
      case-control surveillance of severe cutaneous adverse reactions) study results as
      a reference to define signals. The EB05s were calculated as a cumulative relative
      reporting frequency from 1968 to 3Q2009. RESULTS: Fifty drugs were identified as
      being associated with SJS/TEN. This included 12 "highly suspect" drugs and 36
      "suspect" drugs. Meloxicam was the only drug that appeared on the "highly
      suspect" list from EuroSCAR that did not show a disproportional increase in
      relative reporting frequency (EB05 = 0.734). In addition, several drugs did not
      have an association with SJS/TEN (EB05 < 2). CONCLUSIONS: There was good
      concordance between the reporting frequencies observed in the FDA AERS database
      and the published risk estimation of medications implicated in SJS/TEN.

PMID- 22139992
TI  - Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer: a single
      arm phase II study.
AB  - The purpose of the current phase II single-arm clinical trial was to evaluate
      whether pretreatment with low-dose cyclophosphamide improves immunogenicity of a
      p53-synthetic long peptide (SLP) vaccine in patients with recurrent ovarian
      cancer. Patients with ovarian cancer with elevated serum levels of CA-125 after
      primary treatment were immunized four times with the p53-SLP vaccine. Each
      immunization was preceded by administration of 300 mg/m2 intravenous
      cyclophosphamide as a means to affect regulatory T cells (Tregs). Vaccine-induced
      p53-specific interferon-gamma (IFN-gamma)-producing T cells evaluated by IFN
      gamma ELISPOT were observed in 90% (9/10) and 87.5% (7/8) of evaluable patients
      after two and four immunizations, respectively. Proliferative p53-specific T
      cells, observed in 80.0% (8/10) and 62.5% (5/8) of patients, produced both T
      helper 1 and T-helper-2 cytokines. Cyclophosphamide induced neither a
      quantitative reduction of Tregs determined by CD4+ FoxP3+ T cell levels nor a
      demonstrable qualitative difference in Treg function tested in vitro.
      Nonetheless, the number of vaccine-induced p53-specific IFN-gamma-producing T
      cells was higher in our study compared to a study in which a similar patient
      group was treated with p53-SLP monotherapy (p<=0.012). Furthermore, the strong
      reduction in the number of circulating p53-specific T cells observed previously
      after four immunizations was currently absent. Stable disease was observed in
      20.0% (2/10) of patients, and the remainder of patients (80.0%) showed clinical,
      biochemical and/or radiographic evidence of progressive disease. The outcome of
      this phase II trial warrants new studies on the use of low-dose cyclophosphamide
      to potentiate the immunogenicity of the p53-SLP vaccine or other antitumor
      vaccines.

PMID- 22139993
TI  - Photocrosslinking between peptide-peptide or peptide-oligonucleotide by Ru(II)
      TAP complexes.
AB  - Ru(II)-TAP complexes have been shown to be very attractive compounds in the frame
      of developments of new anticancer drugs targeting the genetic material. This
      increasing interest originates from observations of covalent bond formations,
      triggered by photo-induced electron transfer (PET) between Ru(II)-TAP complexes
      and guanine bases of DNA. This photoreaction has recently been extended to the
      tryptophan (Trp) amino acid for future applications involving peptides. Thus, a
      double photo-addition of Trp residues of peptides on Ru(II) complexes is
      demonstrated by mass spectrometry with some structural issues. Such bi-adduct
      formations offer the possibility of photocrosslinking two Trp-containing
      biomolecules, which is investigated in this study. Thus, photocrosslinking
      between two complementary oligonucleotides (ODNs) derivatized by Trp-containing
      tripeptides is demonstrated by polyacrylamide gel electrophoresis (PAGE) in the
      presence of Ru(II)-TAP complexes. Both PAGE and MS indicate that such
      photocrosslinkings arise from two reaction pathways: either via the double
      addition of Trp residues on the Ru complex or from dimerization of Trp radicals.
      The competition between these two pathways depends on the experimental
      conditions. Heterobridgings between guanine bases and tryptophan residues
      mediated by Ru(II)-TAP complexes is also examined, opening the way to ODN-peptide
      photocrosslinkings.

PMID- 22139994
TI  - A 7-gene signature of the recipient predicts the progression of fibrosis after
      liver transplantation for hepatitis C virus infection.
AB  - Fibrosis recurrence after liver transplantation (LT) for hepatitis C virus (HCV)
      is a universal event and strongly determines a patient's prognosis. The recipient
      risk factors for fibrosis recurrence are still poorly defined. Here we assess a
      genetic risk score as a predictor of fibrosis after LT. The cirrhosis risk score
      (CRS), which comprises allele variants in 7 genes (adaptor-related protein
      complex 3 S2, aquaporin 2, antizyme inhibitor 1, degenerative spermatocyte
      homolog 1 lipid desaturase, syntaxin binding protein 5-like, toll-like receptor
      4, and transient receptor potential cation channel M5), was calculated for 137
      patients who underwent LT for HCV infection and experienced HCV reinfection of
      the graft. The patients were stratified into 3 CRS categories: <0.5, 0.5 to 0.7,
      and >0.7. All patients underwent protocol biopsy after LT (median follow-up = 5
      years), and liver fibrosis was assessed according to the Desmet and Scheuer
      score. The data were analyzed with univariate and multivariate analyses. The
      results showed that the highest CRS category was strongly associated with the
      presence of F2 or F3 fibrosis in protocol biopsy samples 1, 3, and 5 years after
      LT (P = 0.006, P = 0.001, and P = 0.02, respectively). Overall, 75.0% of the
      patients with a CRS > 0.7 developed at least F2 fibrosis, whereas 51.5% developed
      F3 fibrosis during follow-up. The predictive value of the CRS for fibrosis
      progression was independent of known clinical risk factors, including the age of
      the donor, the sex of the recipient, and the occurrence of acute rejection. A
      Kaplan-Meier analysis confirmed the prognostic value of the CRS with respect to
      the recurrence of severe liver fibrosis in HCV-infected patients after LT (log
      rank = 6.23, P = 0.03). In conclusion, the genetic signature of the recipient
      predicts the likelihood of severe liver fibrosis in the graft after HCV
      recurrence. The CRS might help with early clinical decision making (eg, the
      selection of patients for antiviral therapy after LT).

PMID- 22139995
TI  - Molecular modeling to rationalize ligand-support interactions in affinity
      chromatography.
AB  - The development of rational design criteria for synthetic-ligand-based affinity
      chromatography requires a basic comprehension of all the factors influencing the
      binding capacity and selectivity of the stationary phase. In this work, molecular
      dynamics simulations are systematically used to investigate the impact of
      structural modifications of spacer and ligand on ligand-support interactions. The
      investigated ligands are characterized by a triazine core bi-functionalized with
      two amino acid side chains aimed at representing a range of
      hydrophobic/hydrophilic characters. As spacers both literature (1-2-diaminoethane
      and 1,4-substituted [1,2,3]-triazole) and speculative oligopeptidic molecules
      (Gly-[Ala]4-Gly, Gly-[Lys]4-Gly, and Gly-[Glu]4-Gly) have been considered to
      address the role of charges distribution, rigidity, and structural complexity. In
      this investigation, the spacer emerged as a key component: on the one hand, the
      choice of a proper spacer allows improving the hydrophilic character of the
      ligand-spacer adduct without compromising the structure of the affinity ligand,
      while on the other hand the use of structurally complex spacers induces spacer
      support interactions that enhance the degree of solvation of the ligand
      regardless of its hydrophobic character. These findings suggest that the use of
      structured spacers could represent a viable pathway for tailoring the
      performances of affinity chromatography stationary phases.

PMID- 22139996
TI  - Virtual Cell: computational tools for modeling in cell biology.
AB  - The Virtual Cell (VCell) is a general computational framework for modeling
      physicochemical and electrophysiological processes in living cells. Developed by
      the National Resource for Cell Analysis and Modeling at the University of
      Connecticut Health Center, it provides automated tools for simulating a wide
      range of cellular phenomena in space and time, both deterministically and
      stochastically. These computational tools allow one to couple electrophysiology
      and reaction kinetics with transport mechanisms, such as diffusion and directed
      transport, and map them onto spatial domains of various shapes, including
      irregular three-dimensional geometries derived from experimental images. In this
      article, we review new robust computational tools recently deployed in VCell for
      treating spatially resolved models.

PMID- 22139997
TI  - 3D FLAIRED: 3D fluid attenuated inversion recovery for enhanced detection of
      lesions in multiple sclerosis.
AB  - Contrast optimization of a three-dimensional (3D) Fluid-attenuated inversion
      recovery (FLAIR) sequence is examined in the context of multiple sclerosis. In
      order to develop 3D FLAIR for enhanced detection of lesions, an iterative
      approach based on theoretical considerations was used. The 3D FLAIR sequence was
      systematically acquired with incremental parameter changes on a single subject
      with multiple sclerosis in a 3-T MRI scanner. Region of interest analysis was
      performed on the images, and the best estimate of the optimal acquisition
      parameters was established. This process was iterated on subsequent patients with
      multiple sclerosis until only marginal gains in quality were obtained. Three
      dimensional FLAIR for enhanced detection produced increased lesion detection and
      identification in the supratentorial and infratentorial regions when compared
      with default GE 3D FLAIR and two-dimensional FLAIR sequences. Lesion border
      delineation was enhanced as evidenced by better lesion and white matter contrast
      ratios, demonstrating that the approach is a viable method for improved lesion
      detection.

PMID- 22139998
TI  - Fetal hemoglobin in sickle cell anemia: molecular characterization of the
      unusually high fetal hemoglobin phenotype in African Americans.
AB  - Fetal hemoglobin (HbF) is a major modifier of disease severity in sickle cell
      anemia (SCA). Three major HbF quantitative trait loci (QTL) are known: the Xmn I
      site upstream of (G)gamma- globin gene (HBG2) on chromosome 11p15, BCL11A on
      chromosome 2p16, and HBS1L-MYB intergenic polymorphism (HMIP) on chromosome 6q23.
      However, the roles of these QTLs in patients with SCA with uncharacteristically
      high HbF are not known. We studied 20 African American patients with SCA with
      markedly elevated HbF (mean 17.2%). They had significantly higher minor allele
      frequencies (MAF) in two HbF QTLs, BCL11A, and HMIP, compared with those with low
      HbF. A 3-bp (TAC) deletion in complete linkage disequilibrium (LD) with the minor
      allele of rs9399137 in HMIP was also present significantly more often in these
      patients. To further explore other genetic loci that might be responsible for
      this high HbF, we sequenced a 14.1 kb DNA fragment between the (A)gamma-(HBG1)
      and delta-globin genes (HBD). Thirty-eight SNPs were found. Four SNPs had
      significantly higher major allele frequencies in the unusually high HbF group. In
      silico analyses of these four polymorphisms predicted alteration in transcription
      factor binding sites in 3.

PMID- 22140001
TI  - Is a mandatory intensive care unit stay needed after liver transplantation?
      Feasibility of fast-tracking to the surgical ward after liver transplantation.
AB  - The continuation of hemodynamic, respiratory, and metabolic support for a
      variable period after liver transplantation (LT) in the intensive care unit (ICU)
      is considered routine by many transplant programs. However, some LT recipients
      may be liberated from mechanical ventilation shortly after the discontinuation of
      anesthesia. These patients might be appropriately discharged from the
      postanesthesia care unit (PACU) to the surgical ward and bypass the ICU entirely.
      In 2002, our program started a fast-tracking program: select LT recipients are
      transferred from the operating room to the PACU for recovery and tracheal
      extubation with a subsequent transfer to the ward, and the ICU stay is completely
      eliminated. Between January 1, 2003 and December 31, 2007, 1045 patients
      underwent LT at our transplant program; 175 patients were excluded from the
      study. Five hundred twenty-three of the remaining 870 patients (60.10%) were fast
      tracked to the surgical ward, and 347 (39.90%) were admitted to the ICU after LT.
      The failure rate after fast-tracking to the surgical ward was 1.90%. The groups
      were significantly different with respect to the recipient age, the raw Model for
      End-Stage Liver Disease (MELD) score at the time of LT, the recipient body mass
      index (BMI), the retransplantation status, the operative time, the warm ischemia
      time, and the intraoperative transfusion requirements. A multivariate logistic
      regression analysis revealed that the raw MELD score at the time of LT, the
      operative time, the intraoperative transfusion requirements, the recipient age,
      the recipient BMI, and the absence of hepatocellular cancer/cholangiocarcinoma
      were significant predictors of ICU admission. In conclusion, we are reporting the
      largest single-center experience demonstrating the feasibility of bypassing an
      ICU stay after LT.

PMID- 22139999
TI  - Effect of calcium treatment on blood parameters, gonadal development and the
      structure of bone in immature female rats.
AB  - Calcium is an essential nutrient required for critical biological functions.
      Calcium supplementation is to be evaluated using immature female rats. The
      present study focused on some blood parameters, gonadal development and bone
      structure. Forty immature female Sprague-Dawley rats were randomly divided into
      four equal-sized groups (80 g average body weight) to receive calcium chloride
      dihydrate (group I: control; groups II, III and IV: received 20 mg, 40 mg and 60
      mg per kg body weight, respectively) for 5 weeks. Rats were decapitated, and
      their trunk blood was sampled for biochemical assays. Cholesterol, triglycerides,
      glucose and calcium were measured. Gonadal and bone structure were histologically
      evaluated. Results revealed that treatment of developing female rats with three
      calcium doses used have no marked effect on the serum calcium and cholesterol
      levels. However, serum triglyceride level and body weight gain are significantly
      decreased in rats treated with all of the three calcium doses. Serum glucose
      level showed a marked increase in animals treated with the higher calcium doses.
      Moreover, observable histological alterations are recognized in the ovaries.
      Bones of the experimental animals also showed morphological alterations. These
      results suggest that increasing calcium supplementation decreases triglycerides
      and percentage body weight gain and positively affects the bone and gonadal
      development.

PMID- 22140002
TI  - Spina bifida subtypes and sub-phenotypes by maternal race/ethnicity in the
      National Birth Defects Prevention Study.
AB  - Spina bifida refers to a collection of neural tube defects, including
      myelomeningocele, meningocele, and myelocele (SB(M) ), as well as
      lipomyelomeningocele and lipomeningocele (SB(L) ). Maternal race/ethnicity has
      been associated with an increased risk for spina bifida among offspring. To
      better understand this relationship, we evaluated different spina bifida subtypes
      (SB(M) vs. SB(L) ) and sub-phenotypes (anatomic level or presence of additional
      malformations) by maternal race/ethnicity using data from the National Birth
      Defects Prevention Study. This study is a large, multisite, population-based
      study of nonsyndromic birth defects. Prevalence estimates were obtained using
      data from spina bifida cases (live births, fetal deaths, and elective
      terminations) and total live births in the study regions. From October 1997
      through December 2005, 1,046 infants/fetuses with spina bifida were delivered,
      yielding a prevalence of 3.06 per 10,000 live births. Differences in the
      prevalences of SB(M) vs. SB(L) , isolated versus non-isolated SB(M) , and lesion
      level in isolated SB(M) among case offspring were observed by maternal
      race/ethnicity. Compared to non-Hispanic (NH) White mothers, offspring of
      Hispanic mothers had higher prevalences of each subtype and most sub-phenotypes,
      while offspring of NH Black mothers generally had lower prevalences. Furthermore,
      differences in race/ethnicity among those with isolated SB(M) were more
      pronounced by sex. For instance, among male offspring, the prevalence of isolated
      SB(M) was significantly higher for those with Hispanic mothers compared to NH
      White mothers [prevalence ratio (PR): 1.55, 95% confidence interval: 1.23-1.95].
      These findings provide evidence that certain spina bifida subtypes and sub
      phenotypes may be etiologically distinct.

PMID- 22140003
TI  - Un Abrazo Para La Familia: providing low-income Hispanics with education and
      skills in coping with breast cancer and caregiving.
AB  - OBJECTIVE: Un Abrazo Para La Familia (A Hug for the Family) is an intervention
      designed to increase the accessibility of cancer information to low-income and
      medically underserved co-survivors of cancer. Co-survivors are family members or
      friends of an individual diagnosed with cancer. Our goal was to increase socio
      emotional support for these co-survivors and improve skills in coping with
      cancer. The purpose of our pilot study was to explore the effectiveness of the
      intervention in increasing cancer knowledge and self-efficacy among co-survivors.
      METHODS: Un Abrazo consisted of three one-hour sessions, in either Spanish or
      English. Sessions were delivered by a trained promotora (community health
      worker), in partnership with a counselor. Sixty participants completed measures
      of cancer knowledge and self-efficacy preceding (pre-test) and following the
      intervention (post-test). RESULTS: From pre-test to post-test, the percentage of
      questions answered correctly about cancer knowledge increased (p < 0.001), as did
      ratings of self-efficacy (p < 0.001). Decreases were seen in 'Do not know'
      responses for cancer knowledge (p < 0.01), with a negative correlation between
      number of 'Do not knows' on cancer knowledge at pre-test and ratings of self
      efficacy at pre-test (r = -0.47, p < 0.01). CONCLUSIONS: When provided an
      accessible format, co-survivors of cancer from underserved populations increase
      their cancer knowledge and self-efficacy. This is notable because research
      indicates that family members and friends with increased cancer knowledge assume
      more active involvement in the cancer care of their loved ones.

PMID- 22140005
TI  - Do glycosyl sulfonium ions engage in neighbouring-group participation? A study of
      oxathiane glycosyl donors and the basis for their stereoselectivity.
AB  - Neighbouring-group participation has long been used to control the synthesis of
      1,2-trans-glycosides. More recently there has been a growing interest in the
      development of similar strategies for the synthesis of 1,2-cis-glycosides, in
      particular the use of auxiliary groups that generate sulfonium ion intermediates.
      However, there has been some debate over the role of sulfonium ion intermediates
      in these reactions: do sulfonium ions actually engage in neighbouring-group
      participation, or are they a resting state of the system prior to reaction
      through an oxacarbenium ion intermediate? Herein, we describe the reactivities
      and stereoselectivities of a family of bicyclic thioglycosides in which an
      oxathiane ring is fused to the sugar to form a trans-decalin-like structure. A
      methyl sulfonium ion derived from one such glycosyl donor is so stable that it
      can be crystallised from ethanol, yet it reacts with complete stereoselectivity
      at high temperature. The importance of a ketal group in the oxathiane ring for
      maintaining this high stereoselectivity is investigated using a combination of
      experiment and ab initio calculations. The data are discussed in terms of S(N)1
      and S(N)2 type mechanisms. Trends in stereoselectivity across a series of
      compounds are more consistent with selective addition to oxacarbenium ions rather
      than a shift between S(N)1 and S(N)2 mechanisms.

PMID- 22140004
TI  - Understanding suicide risk: identification of high-risk groups during high-risk
      times.
AB  - BACKGROUND: The assessment of suicide risk is a complex task for mental health
      professionals. Certain demographic groups are associated with completed suicide
      including males, divorced adults, and Caucasians. However, demographic variables
      alone provide a crude assessment of suicide risk. Psychiatric diagnosis and
      recent life events might improve the identification of high-risk individuals.
      METHOD: The current study evaluated 148 individuals who died by suicide compared
      with 257 adults who died suddenly from accidents or medical problems.
      Psychological autopsy was used to assess Axis I psychiatric diagnosis and recent
      stressful life events. RESULTS: Suicide completers were significantly more likely
      than comparison subjects to have a depressive disorder, a substance abuse
      disorder, and to have experienced interpersonal conflict in the months leading up
      to their death. A discriminant function analysis revealed that the combination of
      demographic variables, recent stressful life events, and psychiatric diagnoses
      best discriminated between suicide completers and comparison subjects.
      CONCLUSIONS: Proper assessment of suicide risk should include a comprehensive
      evaluation of demographic characteristics, recent life stressors, and psychiatric
      diagnosis.

PMID- 22140006
TI  - New index for assessing the chronotropic response in patients with end-stage
      liver disease who are undergoing dobutamine stress echocardiography.
AB  - The inability to achieve 85% of the maximum predicted heart rate (MPHR) on
      dobutamine stress echocardiography (DSE) is defined as chronotropic incompetence
      and is a predictor of major cardiac events after orthotopic liver transplantation
      (OLT). The majority of patients with end-stage liver disease (ESLD) receive beta
      blockers for the prevention of variceal bleeding. In these patients, it is
      impossible to determine whether chronotropic incompetence is secondary to
      cirrhosis-related autonomic dysfunction or is merely a beta-blocker effect. We
      evaluated the usefulness of the maximum achieved heart rate (MAHR) and the heart
      rate reserve (HRR) in the detection of chronotropic incompetence in ESLD patients
      on beta-blocker therapy before DSE. We also evaluated the usefulness of a new
      index, the modified heart rate reserve (MHRR), in diagnosing chronotropic
      incompetence and predicting major cardiovascular adverse events after OLT. The
      study population consisted of 284 ESLD patients. The mean values of MAHR
      (expressed as a percentage of 85% of MPHR) and HRR were significantly lower for
      patients on beta-blockers versus patients off beta-blockers [97.1% versus 101.6%
      (t = 5.01, P < 0.001) and 71.7% versus 77.3% (t = 4.03, P < 0.001),
      respectively], whereas the values of MHRR were similar in patients on beta
      blockers and patients off beta-blockers [102.3% versus 102.1% (t = 0.04, P =
      0.97)]. A regression analysis showed a significant association of MAHR (P <
      0.001) and HRR (P < 0.001) with beta-blockers, whereas MHRR was not associated
      with beta-blocker treatment (P = 0.92). MAHR and HRR were found to have no value
      for diagnosing chronotropic incompetence in ESLD patients. MHRR was not affected
      by beta-blocker therapy. Patients who developed heart failure (HF) and myocardial
      infarction (MI) after OLT had significantly lower MHRR values according to
      pretransplant DSE. MHRR was significantly associated with the subsequent
      development of HF (P = 0.01) and MI (P = 0.01) after OLT. MHRR may be useful for
      the determination of the target heart rate for stress testing, the diagnosis of
      chronotropic incompetence, and the prediction of adverse cardiac events after
      OLT.

PMID- 22140007
TI  - Determination of sulfonamides in livers using matrix solid-phase dispersion
      extraction high-performance liquid chromatography.
AB  - The matrix solid-phase dispersion (MSPD) was applied for extracting seven
      sulfonamides (SAs) in liver samples. The separation and determination were
      carried out by high-performance liquid chromatography. The analytes were
      derivated with fluorescamine and detected with fluorescence detector. The types
      of dispersion adsorbents for MSPD were examined and the highest recovery was
      obtained when the diatomaceous earth was used as the dispersion adsorbent and the
      mass ratio of dispersion adsorbent to sample was 3:1. The acetone was used as the
      elution solvent. Under the optimal conditions, the linear range for determining
      the SAs in liver samples was 5.0-1000.0 ng/g. The porcine, chicken and cattle
      liver samples were analyzed and the average recoveries of seven SAs were higher
      than 84.6%.

PMID- 22140009
TI  - Septin localization in the dimorphic fungus Paracoccidioides brasiliensis.
AB  - Septins are evolutionarily conserved proteins that contain a GTPase domain and
      are capable of forming filaments at the cell periphery. Septins are involved in
      many essential cellular processes, such as cytokinesis and cell polarization, and
      are used as markers of morphogenesis in several fungi. Dimorphism in fungi
      enables cells to switch between morphologies (yeast or filament forms), due to
      changes in the temperature of the environment. We analysed the localization of
      septin proteins in yeast and filamentous cells of the dimorphic fungus
      Paracoccidioides brasiliensis, a common cause of granulomatous mycosis. In order
      to determine septin localization, we first cloned Cdc12p, a septin homolog from
      P. brasiliensis, and expressed it in Escherichia coli. Following PbCdc12p
      purification, specific serum against PbCdc12p were raised for use in
      immunofluorescence assays. We observed the hourglass and ring forms of septin
      filaments during cell division in yeast. Septin filaments were also
      simultaneously localized in the necks of multiple budding cells. A distinctive
      pattern of punctuate and/or diffuse localization was also seen in the periphery
      of multinucleate yeast cells and at the tips and septa of filamentous cells. A
      more diffuse and punctuate pattern of localization observed in P. brasiliensis
      cells seems to be unique to filamentous and dimorphic fungi and may be related to
      their specialization in cell wall deposition, morphogenesis and cell cycle
      control.

PMID- 22140008
TI  - Computational models for the study of heart-lung interactions in mammals.
AB  - The operation and regulation of the lungs and the heart are closely related. This
      is evident when examining the anatomy within the thorax cavity, in the brainstem
      and in the aortic and carotid arteries where chemoreceptors and baroreceptors,
      which provide feedback affecting the regulation of both organs, are concentrated.
      This is also evident in phenomena such as respiratory sinus arrhythmia where the
      heart rate increases during inspiration and decreases during expiration, in other
      types of synchronization between the heart and the lungs known as
      cardioventilatory coupling and in the association between heart failure and sleep
      apnea where breathing is interrupted periodically by periods of no-breathing. The
      full implication and physiological significance of the cardiorespiratory coupling
      under normal, pathological, or extreme physiological conditions are still unknown
      and are subject to ongoing investigation both experimentally and theoretically
      using mathematical models. This article reviews mathematical models that take
      heart-lung interactions into account. The main ideas behind low dimensional,
      phenomenological models for the study of the heart-lung synchronization and sleep
      apnea are described first. Higher dimensions, physiology-based models are
      described next. These models can vary widely in detail and scope and are
      characterized by the way the heart-lung interaction is taken into account: via
      gas exchange, via the central nervous system, via the mechanical interactions,
      and via time delays. The article emphasizes the need for the integration of the
      different sources of heart-lung coupling as well as the different mathematical
      approaches.

PMID- 22140010
TI  - Ultrasound-based transient elastography for the detection of hepatic fibrosis in
      patients with recurrent hepatitis C virus after liver transplantation: a
      systematic review and meta-analysis.
AB  - Ultrasound-based transient elastography (TE) is a promising noninvasive
      alternative to liver biopsy for the detection of hepatic fibrosis due to
      recurrent hepatitis C virus (HCV) after liver transplantation (LT). However, its
      overall test performance in various settings remains unknown. The aim of this
      study was to perform a systematic review and diagnostic accuracy meta-analysis of
      studies comparing ultrasound-based TE to liver biopsy for the detection of
      hepatic fibrosis due to a recurrent HCV infection after LT. Electronic and manual
      bibliographic searches (including scientific abstracts) were performed to
      identify potential studies. A meta-analysis was conducted to generate pooled
      estimates of the sensitivity values, specificity values, likelihood ratios, and
      diagnostic odds ratios of individual studies. The extent of the heterogeneity and
      the reasons for it were assessed. Six fully published studies were identified for
      analysis. Five studies that evaluated significant fibrosis were identified. Among
      these studies, the pooled estimates were 83% for sensitivity [95% confidence
      interval (CI) = 77%-88%], 83% for specificity (95% CI = 77%-88%), 4.95 for the
      positive likelihood ratio (95% CI = 3.4-7.2), 0.17 for the negative likelihood
      ratio (95% CI = 0.09-0.35), and 30.5 for the diagnostic odds ratio (95% CI = 12.8
      72.4). For the 5 studies that assessed cirrhosis, the pooled estimates were 98%
      for sensitivity (95% CI = 90%-100%), 84% for specificity (95% CI = 80%-88%), 7
      for the positive likelihood ratio (95% CI = 2.8-17.3), 0.06 for the negative
      likelihood ratio (95% CI = 0.02-0.19), and 130 for the diagnostic odds ratio (95%
      CI = 36.5-462.1). A diagnostic threshold (or cutoff value) bias was identified as
      an important cause of heterogeneity for the pooled results of both patient
      groups. In conclusion, ultrasound-based TE has excellent diagnostic accuracy for
      identifying cirrhosis due to a recurrent HCV infection after LT. The detection of
      significant fibrosis is more accurate for these patients versus patients whose
      native liver is chronically infected with HCV.

PMID- 22140011
TI  - SMC1A codon 496 mutations affect the cellular response to genotoxic treatments.
AB  - Cornelia de Lange syndrome is a pleiotropic developmental syndrome characterized
      by growth and cognitive impairment, facial dysmorphic features, limb anomalies,
      and other malformations. Mutations in core cohesin genes SMC1A and SMC3, and the
      cohesin regulatory gene, NIPBL, have been identified in Cornelia de Lange
      syndrome probands. Patients with NIPBL mutations have more severe phenotypes when
      compared to those with mutations in SMC1A or SMC3. To date, 26 distinct SMC1A
      mutations have been identified in patients with Cornelia de Lange syndrome. Here,
      we describe a 3-year-old girl with psychomotor and cognitive impairment, mild
      facial dysmorphic features but no limb anomaly, heterozygous for a c.1487G>A
      mutation in SMC1A which predicts p.Arg496His. We show that this mutation leads to
      an impairment of the cellular response to genotoxic treatments.

PMID- 22140012
TI  - General bottom-up construction of spherical particles by pulsed laser irradiation
      of colloidal nanoparticles: a case study on CuO.
AB  - The development of a general method to fabricate spherical semiconductor and
      metal particles advances their promising electrical, optical, magnetic,
      plasmonic, thermoelectric, and optoelectric applications. Herein, by using CuO as
      an example, we systematically demonstrate a general bottom-up laser processing
      technique for the synthesis of submicrometer semiconductor and metal colloidal
      spheres, in which the unique selective pulsed heating assures the formation of
      spherical particles. Importantly, we can easily control the size and phase of
      resultant colloidal spheres by simply tuning the input laser fluence. The heating
      melting-fusion mechanism is proposed to be responsible for the size evolution of
      the spherical particles. We have systematically investigated the influence of
      experimental parameters, including laser fluence, laser wavelength, laser
      irradiation time, dispersing liquid, and starting material concentration on the
      formation of colloidal spheres. We believe that this facile laser irradiation
      approach represents a major step not only for the fabrication of colloidal
      spheres but also in the practical application of laser processing for micro- and
      nanomaterial synthesis.

PMID- 22140013
TI  - Living donor liver transplantation versus deceased donor liver transplantation
      for hepatocellular carcinoma: comparable survival and recurrence.
AB  - Several studies have reported higher rates of recurrent hepatocellular carcinoma
      (HCC) after living donor liver transplantation (LDLT) versus deceased donor liver
      transplantation (DDLT). It is unclear whether this difference is due to a
      specific biological effect unique to the LDLT procedure or to other factors such
      as patient selection. We compared the overall survival (OS) rates and the rates
      of HCC recurrence after LDLT and DDLT at our center. Between January 1996 and
      September 2009, 345 patients with HCC were identified: 287 (83%) had DDLT and 58
      (17%) had LDLT. The OS rates were calculated with the Kaplan-Meier method,
      whereas competing risks methods were used to determine the HCC recurrence rates.
      The LDLT and DDLT groups were similar with respect to most clinical parameters,
      but they had different median waiting times (3.1 versus 5.3 months, P = 0.003)
      and median follow-up times (30 versus 38.1 months, P = 0.02). The type of
      transplant did not affect any of the measured cancer outcomes. The OS rates at 1,
      3, and 5 years were equivalent: 91.3%, 75.2%, and 75.2%, respectively, for the
      LDLT group and 90.5%, 79.7%, and 74.6%, respectively, for DDLT (P = 0.62). The 1
      , 3-, and 5-year HCC recurrence rates were also similar: 8.8%, 10.7%, and 15.4%,
      respectively, for the LDLT group and 7.5%, 14.8%, and 17.0%, respectively, for
      the DDLT group (P = 0.54). A regression analysis identified microvascular
      invasion (but not the graft type) as a predictor of HCC recurrence. In
      conclusion, in well-matched cohorts of LDLT and DDLT recipients, LDLT and DDLT
      provide similarly low recurrence rates and high survival rates for the treatment
      of HCC.

PMID- 22140014
TI  - Associations among parenting experiences during childhood and adolescence,
      hypothalamus-pituitary-adrenal axis hypoactivity, and hippocampal gray matter
      volume reduction in young adults.
AB  - Recent human studies have indicated that adverse parenting experiences during
      childhood and adolescence are associated with adulthood hypothalamus-pituitary
      adrenal (HPA) axis hypoactivity. Chronic HPA axis hypoactivity inhibits
      hippocampal gray matter (GM) development, as shown by animal studies. However,
      associations among adverse parenting experiences during childhood and
      adolescence, HPA axis activity, and brain development, particularly hippocampal
      development, are insufficiently investigated in humans. In this voxel-based
      structural magnetic resonance imaging study, using a cross-sectional design, we
      examined the associations among the scores of parental bonding instrument (PBI; a
      self-report scale to rate the attitudes of parents during the first 16 years),
      cortisol response determined by the dexamethasone/corticotropin-releasing hormone
      test, and regional or total hippocampal GM volume in forty healthy young adults
      with the following features: aged between 18 and 35 years, no cortisol
      hypersecretion in response to the dexamethasone test, no history of traumatic
      events, or no past or current conditions of significant medical illness or
      neuropsychiatric disorders. As a result, parental overprotection scores
      significantly negatively correlated with cortisol response. Additionally, a
      significant positive association was found between cortisol response and total or
      regional hippocampal GM volume. No significant association was observed between
      PBI scores and total or regional hippocampal GM volume. In conclusion,
      statistical associations were found between parental overprotection during
      childhood and adolescence and adulthood HPA axis hypoactivity, and between HPA
      axis hypoactivity and hippocampal GM volume reduction in healthy young adults,
      but no significant relationship was observed between any PBI scores and adulthood
      hippocampal GM volume.

PMID- 22140017
TI  - Novel approaches for drug delivery systems in nanomedicine: effects of particle
      design and shape.
AB  - The identification of novel drug candidates for the treatment of diseases like
      cancer, infectious diseases, or allergies (especially asthma) assigns new tasks
      for pharmaceutical technology. With respect to drug delivery several problems
      occur such as low solubility and hence low bioavailability or restriction to
      inconvenient routes of administration. Nanotechnological approaches promise to
      circumvent some of these problems, therefore being well suited for future
      applications as nanomedicines. Furthermore, efficient and sufficient loading is a
      critical issue that is approached through mesoporous particles and/or through
      nonspherical particles both offering larger volumes and surfaces. Special
      interest is laid on the effect of shape of particulate materials on the body and
      related physiological mechanisms. The modified response of biological systems on
      different shapes opens a new dimension to adjust particle system interaction.
      Finally, the biological response to these systems will determine the fate with
      respect to their therapeutic value. Therefore, the interaction pattern between
      nonspherical particulate materials and biological systems as well as the
      production processes are highlighted.

PMID- 22140020
TI  - Trends in cytogenetic testing and identification of chromosomal abnormalities
      among pregnancies and children with birth defects, metropolitan Atlanta, 1968
      2005.
AB  - The purpose of this study was to examine changes in the use of cytogenetic
      testing and identification of chromosomal abnormalities among pregnancies and
      children with birth defects. Utilizing data from 1968 to 2005 from the
      Metropolitan Atlanta Congenital Defects Program, we analyzed trends in the
      frequency and timing (prenatal or postnatal) of cytogenetic testing and the
      prevalence of recognized chromosome abnormalities among pregnancies and children
      with birth defects (n = 51,424). Cytogenetic testing of pregnancies and children
      with birth defects increased from 7.2% in 1968 to 25.0% in 2005, as did the
      identification of chromosomal abnormalities (2.2% in 1968 to 6.8% in 2005). The
      use of prenatal cytogenetic testing decreased from 1996 to 2005 among women aged
      >=35 years. Identification of chromosomal abnormalities in pregnancies and
      children with birth defects increased from 1968 to 2005, possibly due to
      increased testing, improved diagnostic techniques, or increasing maternal age.
      The decline in prenatal cytogenetic testing observed among mothers aged >=35
      years may be related to the availability of improved prenatal screening
      techniques, resulting in a reduction in the utilization of invasive diagnostic
      tests.

PMID- 22140021
TI  - Donation after cardiac death liver transplantation: time for policy to catch up
      with practice.

PMID- 22140019
TI  - Recipient-donor race mismatch for African American liver transplant patients with
      chronic hepatitis C.
AB  - African American (AA) recipient-donor race mismatch has been associated with
      graft loss and mortality, but studies of an association between race mismatch and
      hepatitis C virus (HCV) disease severity are lacking. HCV-infected adults from 4
      US centers who underwent liver transplantation for the first time (n = 1093) were
      followed for a median of 3.05 years to determine the rates of advanced HCV
      disease (bridging fibrosis or cirrhosis) and graft failure; 11% of the patients
      were AA. The unadjusted cumulative rate of advanced fibrosis was higher in AAs
      than non-AAs (56% and 40% at 4 years, respectively, (P < 0.01), and 59% and 56%
      for AA recipient-donor-matched patients and AA recipient-donor-mismatched
      patients, respectively (P = 0.89). In adjusted models, both AA recipient race
      [hazard ratio (HR) = 1.47, 95% CI = 1.06-2.03, P = 0.02] and AA recipient-donor
      mismatch (versus match; HR = 1.48, 95% CI = 1.03-2.12, P = 0.03) were significant
      predictors of advanced fibrosis; other independent predictors were donor age (HR
      = 1.21, P < 0.01) and cytomegalovirus infection (HR = 1.55, P < 0.01). The 4-year
      unadjusted cumulative rates for HCV-associated graft loss were 10% and 17% for
      non-AAs and AAs, respectively (P < 0.01), and 0% and 21% for AA recipient-donor
      matched patients and AA recipient-donor-mismatched patients, respectively (P <
      0.01). In adjusted models, AA recipient-donor-mismatched patients had a 62%
      higher rate of graft loss than non-AA recipients (HR = 1.62, 95% CI = 1.14-2.29,
      P < 0.01), and AA recipient-donor-matched patients had a 76% lower rate of graft
      loss/mortality (HR = 0.24, 95% CI = 0.06-0.97, P = 0.05). In conclusion, AA
      recipient-donor-mismatched patients who are infected with HCV are at high risk
      for advanced HCV disease and HCV-related graft loss and constitute a patient
      group that will benefit from new therapeutic strategies for preventing graft
      loss.

PMID- 22140022
TI  - Heritability of volumetric brain changes and height in children entering puberty.
AB  - The human brain undergoes structural changes in children entering puberty, while
      simultaneously children increase in height. It is not known if brain changes are
      under genetic control, and whether they are related to genetic factors
      influencing the amount of overall increase in height. Twins underwent magnetic
      resonance imaging brain scans at age 9 (N = 190) and 12 (N = 125). High
      heritability estimates were found at both ages for height and brain volumes (49
      96%), and high genetic correlation between ages were observed (r(g) > 0.89). With
      increasing age, whole brain (+1.1%), cerebellum (+4.2%), cerebral white matter
      (+5.1%), and lateral ventricle (+9.4%) volumes increased, and third ventricle (
      4.0%) and cerebral gray matter (-1.6%) volumes decreased. Children increased on
      average 13.8 cm in height (9.9%). Genetic influences on individual difference in
      volumetric brain and height changes were estimated, both within and across
      traits. The same genetic factors influenced both cerebral (20% heritable) and
      cerebellar volumetric changes (45%). Thus, the extent to which changes in
      cerebral and cerebellar volumes are heritable in children entering puberty are
      due to the same genes that influence change in both structures. The increase in
      height was heritable (73%), and not associated with cerebral volumetric change,
      but positively associated with cerebellar volume change (r(p) = 0.24). This
      association was explained by a genetic correlation (r(g) = 0.48) between height
      and cerebellar change. Brain and body each expand at their own pace and through
      separate genetic pathways. There are distinct genetic processes acting on
      structural brain development, which cannot be explained by genetic increase in
      height.

PMID- 22140023
TI  - The overlooked difference between human endogenous and recombinant
      erythropoietins and its implication for sports drug testing and pharmaceutical
      drug design.
AB  - Sequential deglycosylation by exoglycosidase treatment (Reagent Array Analysis
      Method, RAAM) and subsequent sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) revealed a profound structural difference between
      human endogenous and recombinant erythropoietins. While both proteins behaved
      similarly upon digestion with Arthrobacter ureafaciens alpha-sialidase and
      Steptococcus pneumoniae beta-D-galactosidase, the action of N-acetyl-beta-D
      glucosaminidase from Steptococcus pneumoniae was partly blocked by endogenous but
      not recombinant erythropoietins. Consequently, further treatment with Jack bean
      alpha-D-mannosidase and Helix pomatia beta-D-mannosidase led to only very limited
      additional deglycosylation of endogenous EPO, while rhEPO glycans continued to be
      degraded. The behaviour was visualized by SDS-PAGE combined with Western
      blotting. While the apparent molecular masses of most endogenous glycoforms did
      not further decrease after treatment with the first three enzymes, masses of most
      rhEPO glycoforms continued to drop after digestion with the two mannosidases.
      Both, human urinary and serum EPO showed this blocking effect, and all of the
      tested 28 recombinant epoetins were accessible to further degradation by exo
      mannosidases. The majority of EPO pharmaceuticals is produced in Chinese hamster
      ovary (CHO) cell lines, few in other ones (i.e. baby hamster kidney (BHK) or
      human fibrosarcoma (HT-1080) cells). Since human endogenous EPO is primarily
      produced by the kidneys, tissue specific glycosylation might explain the altered
      deglycosylation behaviour. This difference was overlooked since EPO was first
      isolated from human urine in 1977. The results might prove useful for anti-doping
      testing and future EPO drug development.

PMID- 22140024
TI  - Impact of neoadjuvant chemoradiation on the tumor burden before liver
      transplantation for unresectable cholangiocarcinoma.
AB  - The very early experience with liver transplantation (LT) for cholangiocarcinoma
      (CC) was dismal because of the poor survival outcomes and the high recurrence
      rates. However, LT for CC in conjunction with neoadjuvant chemoradiation recently
      has shown encouraging results, although the data are extremely limited. At our
      institution between 2001 and 2008, 22 CC patients underwent protocol orthotopic
      LT at a median age of 45 years (range = 24-63 years). At a median follow-up of
      601.5 days (range = 111-1388 days), the median survival time of the cohort was
      3.3 years. The 1-, 2-, and 3-year Kaplan-Meier survival probabilities were 90%,
      70%, and 63%, respectively, whereas the historical 5-year survival rates were 0%
      to 18% for intrahepatic CC and 23% to 26% for extrahepatic CC when patients
      underwent transplantation without neoadjuvant therapy. These encouraging survival
      rates for patients with this type of tumor, which is difficult to diagnose and
      treat, are no less significant when they are compared to the national 1- and 3
      year survival rates (86% and 68%, respectively) of patients undergoing deceased
      donor LT for malignant neoplasms of the liver (as reported by the United Network
      for Organ Sharing). In our series, disease recurrence was significantly
      associated with a larger residual tumor [6.3 versus 2.0 cm (mean values), P =
      0.008] and with a shorter waiting time for LT after the chemoradiation protocol
      [18 versus 56 days (mean values), P = 0.04]. Our LT protocol for CC was found to
      be promising for patients with truly extrahepatic CC and for patients within
      stages I to IIB of the American Joint Committee on Cancer Staging system (100%
      survival at a median follow-up of 2.2 years), but the results were notably poor
      for patients with stage III extrahepatic CC (median survival = 1.2 years). These
      observations highlight the need for accurate preoperative staging of CC for ideal
      LT recipient selection and the importance of a low tumor burden and a longer wait
      after neoadjuvant therapy. More effective chemoradiation regimens for reducing
      the tumor burden and the appropriate timing of LT after neoadjuvant
      chemoradiation require further research.

PMID- 22140025
TI  - The 8th international research symposium on the Marfan syndrome and related
      conditions.
AB  - In the nearly quarter-century since the first international symposium on Marfan
      syndrome, enormous progress has been achieved in clinical, translational, and
      basic research. The 8th symposium, at the end of 2010, provides a useful summary
      of the current status of investigations, reveals why life-expectancy has improved
      so markedly during the past 30 years, and lays out a clear path for future
      endeavors, not only in Marfan syndrome, but in the expanding array of conditions
      related either through phenotype or pathogenesis.

PMID- 22140029
TI  - Longitudinally guided level sets for consistent tissue segmentation of neonates.
AB  - Quantification of brain development as well as disease-induced pathologies in
      neonates often requires precise delineation of white matter, grey matter and
      cerebrospinal fluid. Unlike adults, tissue segmentation in neonates is
      significantly more challenging due to the inherently lower tissue contrast. Most
      existing methods take a voxel-based approach and are limited to working with
      images from a single time-point, even though longitudinal scans are available. We
      take a different approach by taking advantage of the fact that the pattern of the
      major sulci and gyri are already present in the neonates and generally preserved
      but fine-tuned during brain development. That is, the segmentation of late-time
      point image can be used to guide the segmentation of neonatal image. Accordingly,
      we propose a novel longitudinally guided level-sets method for consistent
      neonatal image segmentation by combining local intensity information, atlas
      spatial prior, cortical thickness constraint, and longitudinal information into a
      variational framework. The minimization of the proposed energy functional is
      strictly derived from a variational principle. Validation performed on both
      simulated and in vivo neonatal brain images shows promising results.

PMID- 22140030
TI  - Human immunodeficiency virus-infected patients undergoing liver transplantation
      are at high risk of vascular complications: true or not?

PMID- 22140031
TI  - A 16q12 microdeletion in a boy with severe psychomotor delay, craniofacial
      dysmorphism, brain and limb malformations, and a heart defect.
AB  - Interstitial deletions of the proximal chromosome 16q are rare. To date, only six
      cases with molecularly well-characterized microdeletions within this chromosomal
      region have been described. We report on a patient with severe psychomotor delay,
      dysmorphic features, microcephaly and hypoplasia of the corpus callosum,
      epilepsy, a heart defect, and pronounced muscular hypotonia. Array comparative
      genomic hybridization (aCGH) revealed that the patient's features were likely
      caused by a 4.7 Mb de novo deletion on chromosome 16q12.1q12.2, which was
      confirmed by quantitative real-time PCR (qPCR). The psychomotor delay and
      craniofacial dysmorphism are more severe in our patient than previously reported
      patients. Unmasked recessive mutations in the ZNF423 and FTO genes on the
      remaining allele were excluded as the putative cause for this severe phenotype.
      In conclusion, the phenotypic spectrum of microdeletions in 16q12 is broad and
      comprises variable degrees of psychomotor delay and intellectual disability,
      craniofacial anomalies, and additional features, including heart defects, brain
      malformations, and limb anomalies.

PMID- 22140032
TI  - Investigating the assumption of homogeneity of treatment effects in clinical
      studies with application to meta-analysis.
AB  - An important part of the evaluation of a therapy is an investigation of the
      assumption of homogeneity of its effect across pre-defined subpopulations. In
      this paper we describe simple graphical presentations that could be used to
      assess the homogeneity of treatment effect and identify outliers. The emphasis in
      the paper is on meta-analysis but the methods described can be generalized to
      other investigations.

PMID- 22140033
TI  - Progression of polycystic disease of the liver after transplantation.

PMID- 22140034
TI  - A mechanistic study on the effect of dexamethasone in moderating cell death in
      Chinese Hamster Ovary cell cultures.
AB  - Dexamethasone (DEX) was previously shown (Jing et al., Biotechnol Bioeng.
      2010;107:488-496) to play a dual role in increasing sialylation of recombinant
      glycoproteins produced by Chinese Hamster Ovary (CHO) cells. DEX addition
      increased sialic acid levels of a recombinant fusion protein through increased
      expression of alpha2,3-sialyltransferase and beta1,4-galactosyltransferase, but
      also decreased the sialidase-mediated, extracellular degradation of sialic acid
      through slowing cell death at the end of the culture period. This study examines
      the underlying mechanism for this cytoprotective action by studying the
      transcriptional response of the CHO cell genome upon DEX treatment using DNA
      microarrays and gene ontology term analysis. Many of those genes showing a
      significant transcriptional response were associated with the regulation of
      programmed cell death. The gene with the highest change in expression level, as
      validated by Quantitative PCR assays with TaqMan(r) probes and confirmed by
      Western Blot analysis, was the antiapoptotic gene Tsc22d3, also referred to as
      GILZ (glucocorticoid-induced leucine zipper). The pathway by which DEX suppressed
      cell death towards the end of the culture period was also confirmed by showing
      involvement of glucocorticoid receptors and GILZ through studies using the
      glucocorticoid antagonist mifepristone (RU-486). These findings advance the
      understanding of the mechanism by which DEX suppresses cell death in CHO cells
      and provide a rationale for the application of glucocorticoids in CHO cell
      culture processes.

PMID- 22140035
TI  - CDKN1C mutations and genital anomalies.

PMID- 22140036
TI  - Why a Bayesian approach to safety analysis in pharmacovigilance is important.
AB  - Large databases of routinely collected data are a valuable source of information
      for detecting potential associations between drugs and adverse events (AE). A
      pharmacovigilance system starts with a scan of these databases for potential
      signals of drug-AE associations that will subsequently be examined by experts to
      aid in regulatory decision-making. The signal generation process faces some key
      challenges: (1) an enormous volume of drug-AE combinations need to be tested
      (i.e. the problem of multiple testing); (2) the results are not in a format that
      allows the incorporation of accumulated experience and knowledge for future
      signal generation; and (3) the signal generation process ignores information
      captured from other processes in the pharmacovigilance system and does not allow
      feedback. Bayesian methods have been developed for signal generation in
      pharmacovigilance, although the full potential of these methods has not been
      realised. For instance, Bayesian hierarchical models will allow the incorporation
      of established medical and epidemiological knowledge into the priors for each
      drug-AE combination. Moreover, the outputs from this analysis can be incorporated
      into decision-making tools to help in signal validation and posterior actions to
      be taken by the regulators and companies. We discuss in this paper the apparent
      advantage of the Bayesian methods used in safety signal generation and the
      similarities and differences between the two widely used Bayesian methods. We
      will also propose the use of Bayesian hierarchical models to address the three
      key challenges and discuss the reasons why Bayesian methodology still have not
      been fully utilised in pharmacovigilance activities.

PMID- 22140037
TI  - Changes in eNOS phosphorylation contribute to increased arteriolar NO release
      during juvenile growth.
AB  - Nitric oxide (NO) mediates a major portion of arteriolar endothelium-dependent
      dilation in adults, but indirect evidence has suggested that NO contributes
      minimally to these responses in the young. Isolated segments of arterioles were
      studied in vitro to verify this age-related increase in NO release and
      investigate the mechanism by which it occurs. Directly measured NO release
      induced by ACh or the Ca(2+) ionophore A-23187 was five- to sixfold higher in
      gracilis muscle arterioles from 42- to 46-day-old (juvenile) rats than in those
      from 25- to 28-day-old (weanling) rats. There were no differences between groups
      in arteriolar endothelial NO synthase (eNOS) expression or tetrahydrobiopterin
      levels, and arteriolar l-arginine levels were lower in juvenile vessels than in
      weanling vessels (104 +/- 6 vs.126 +/- 3 pmol/mg). In contrast, agonist-induced
      eNOS Thr(495) dephosphorylation and eNOS Ser(1177) phosphorylation (events
      required for maximal activity) were up to 30% and 65% greater, respectively, in
      juvenile vessels. Juvenile vessels did not show increased expression of enzymes
      that mediate these events [protein phosphatases 1 and 2A and PKA and PKB (Akt)]
      or heat shock protein 90, which facilitates Ser(1177) phosphorylation. However,
      agonist-induced colocalization of heat shock protein 90 with eNOS was 34-66%
      greater in juvenile vessels than in weanling vessels, and abolition of this
      difference with geldanamycin also abolished the difference in Ser(1177)
      phosphorylation between groups. These findings suggest that growth-related
      increases in arteriolar NO bioavailability may be due at least partially to
      changes in the regulation of eNOS phosphorylation and increased signaling
      activity, with no change in the abundance of eNOS signaling proteins.

PMID- 22140038
TI  - Increased arterial smooth muscle Ca2+ signaling, vasoconstriction, and myogenic
      reactivity in Milan hypertensive rats.
AB  - The Milan hypertensive strain (MHS) rats are a genetic model of hypertension with
      adducin gene polymorphisms linked to enhanced renal tubular Na(+) reabsorption.
      Recently we demonstrated that Ca(2+) signaling is augmented in freshly isolated
      mesenteric artery myocytes from MHS rats. This is associated with greatly
      enhanced expression of Na(+)/Ca(2+) exchanger-1 (NCX1), C-type transient receptor
      potential (TRPC6) protein, and sarco(endo)plasmic reticulum Ca(2+)-ATPase
      (SERCA2) compared with arteries from Milan normotensive strain (MNS) rats. Here,
      we test the hypothesis that the enhanced Ca(2+) signaling in MHS arterial smooth
      muscle is directly reflected in augmented vasoconstriction [myogenic and
      phenylephrine (PE)-evoked responses] in isolated mesenteric small arteries.
      Systolic blood pressure was higher in MHS (145 +/- 1 mmHg) than in MNS (112 +/- 1
      mmHg; P < 0.001; n = 16 each) rats. Pressurized mesenteric resistance arteries
      from MHS rats had significantly augmented myogenic tone and reactivity and
      enhanced constriction to low-dose (1-100 nM) PE. Isolated MHS arterial myocytes
      exhibited approximately twofold increased peak Ca(2+) signals in response to 5
      MUM PE or ATP in the absence and presence of extracellular Ca(2+). These
      augmented responses are consistent with increased vasoconstrictor-evoked
      sarcoplasmic reticulum (SR) Ca(2+) release and increased Ca(2+) entry,
      respectively. The increased SR Ca(2+) release correlates with a doubling of
      inositol 1,4,5-trisphosphate receptor type 1 and tripling of SERCA2 expression.
      Pressurized MHS arteries also exhibited a ~70% increase in 100 nM ouabain-induced
      vasoconstriction compared with MNS arteries. These functional alterations reveal
      that, in a genetic model of hypertension linked to renal dysfunction, multiple
      mechanisms within the arterial myocytes contribute to enhanced Ca(2+) signaling
      and myogenic and vasoconstrictor-induced arterial constriction. MHS rats have
      elevated plasma levels of endogenous ouabain, which may initiate the protein
      upregulation and enhanced Ca(2+) signaling. These molecular and functional
      changes provide a mechanism for the increased peripheral vascular resistance
      (whole body autoregulation) that underlies the sustained hypertension.

PMID- 22140039
TI  - Altered clock gene expression and vascular smooth muscle diurnal contractile
      variations in type 2 diabetic db/db mice.
AB  - This study was designed to determine whether the 24-h rhythms of clock gene
      expression and vascular smooth muscle (VSM) contractile responses are altered in
      type 2 diabetic db/db mice. Control and db/db mice were euthanized at 6-h
      intervals throughout the day. The aorta, mesenteric arteries, heart, kidney, and
      brain were isolated. Clock and target gene mRNA levels were determined by either
      real-time PCR or in situ hybridization. Isometric contractions were measured in
      isolated aortic helical strips, and pressor responses to an intravenous injection
      of vasoconstrictors were determined in vivo using radiotelemetry. We found that
      the 24-h mRNA rhythms of the following genes were suppressed in db/db mice
      compared with control mice: the clock genes period homolog 1/2 (Per1/2) and
      cryptochrome 1/2 (Cry1/2) and their target genes D site albumin promoter-binding
      protein (Dbp) and peroxisome proliferator-activated receptor-gamma (Pparg) in the
      aorta and mesenteric arteries; Dbp in the heart; Per1, nuclear receptor subfamily
      1, group D, member 1 (Rev-erba), and Dbp in the kidney; and Per1 in the
      suprachiasmatic nucleus. The 24-h contractile variations in response to
      phenylephrine (alpha(1)-agonist), ANG II, and high K(+) were significantly
      altered in the aortas from db/db mice compared with control mice. The diurnal
      variations of the in vivo pressor responses to phenylephrine and ANG II were lost
      in db/db mice. Moreover, the 24-h mRNA rhythms of the contraction-related
      proteins Rho kinase 1/2, PKC-potentiated phosphatase inhibitory protein of 17
      kDa, calponin-3, tropomyosin-1/2, and smooth muscle protein 22-alpha were
      suppressed in db/db mice compared with control mice. Together, our data
      demonstrated that the 24-h rhythms of clock gene mRNA, mRNA levels of several
      contraction-related proteins, and VSM contraction were disrupted in db/db mice,
      which may contribute to the disruption of their blood pressure circadian rhythm.

PMID- 22140040
TI  - Subtotal nephrectomy plus coronary ligation leads to more pronounced damage in
      both organs than either nephrectomy or coronary ligation.
AB  - Coexistence of chronic kidney disease (CKD) and heart failure (HF) in humans is
      associated with poor outcome. We hypothesized that preexistent CKD worsens
      cardiac outcome after myocardial infarction, and conversely that ensuing HF
      worsens progression of CKD. Subtotally nephrectomized (SNX) or sham-operated
      (CON) rats were subjected to coronary ligation (CL) or sham surgery in week 9 to
      realize four groups: CON, SNX, CON + CL, and SNX + CL. Blood pressure and renal
      function were measured in weeks 8, 11, 13, and 15. In week 16, cardiac
      hemodynamics and end-organ damage were assessed. Blood pressure was significantly
      lower in SNX + CL vs. SNX. Despite this, glomerulosclerosis was more severe in
      SNX + CL vs. SNX. Two weeks after CL, SNX + CL had more cardiac dilatation
      compared with CON + CL (end-diastolic volume index: 0.28 +/- 0.04 vs. 0.19 +/-
      0.03 ml/100 g body wt; mean +/- SD, P < 0.001), although infarct size was
      similar. During follow-up in SNX + CL, ejection fraction declined. Mortality was
      only observed in SNX + CL (2 out of 9). In SNX + CL, end-diastolic pressure (18
      +/- 4 mmHg) and tau (29 +/- 9 ms), the time constant of active relaxation, were
      significantly higher compared with SNX (13 +/- 3 mmHg, 20 +/- 4 ms; P < 0.01) and
      CON + CL (11 +/- 5 mmHg, 17 +/- 2 ms; P < 0.01). The diameter of small arterioles
      in the myocardium was significantly decreased in SNX + CL vs. CON + CL (P <
      0.01). Urinary excretion of NO metabolites was significantly lower in SNX + CL
      compared with both CL and SNX. This study demonstrates the existence of more
      heart and more kidney damage in a new model of combined CKD and HF than in the
      individual models. Such enhanced damage appears to be separate from systemic
      hemodynamic changes. Reduced nitric oxide availability may have played a role in
      both worsened glomerulosclerosis and cardiac diastolic function and appears to be
      a connector in the cardiorenal syndrome.

PMID- 22140041
TI  - PVN adenovirus-siRNA injections silencing either NOX2 or NOX4 attenuate
      aldosterone/NaCl-induced hypertension in mice.
AB  - Mineralocorticoid excess increases superoxide production by activating NADPH
      oxidase (NOX), and intracerebroventricular infusions of NADPH oxidase inhibitors
      attenuate aldosterone (Aldo)/salt-induced hypertension. It has been hypothesized
      that increased reactive oxygen species (ROS) in the brain may be a key mechanism
      in the development of hypertension. The present study investigated the brain
      regional specificity of NADPH oxidase and the role of NOX2 and NOX4 NADPH oxidase
      subunits in the hypothalamic paraventricular nucleus (PVN) in Aldo/salt-induced
      hypertension. PVN injections of adenoviral vectors expressing small interfering
      (si)RNA targeting NOX2 (AdsiRNA-NOX2) or NOX4 (AdsiRNA-NOX4) mRNAs were used to
      knock down NOX2 and NOX4 proteins. Three days later, delivery of Aldo (0.2 mg.kg(
      1).day(-1) sc) via osmotic pump commenced and 1% NaCl was provided in place of
      water. PVN injections of either AdsiRNA-NOX2 or AdsiRNA-NOX4 significantly
      attenuated the development of Aldo/NaCl-induced hypertension. In an additional
      study, Aldo/salt-induced hypertension was also significantly attenuated in NOX2
      (genomic) knockout mice compared with wild-type controls. When animals from both
      functional studies underwent ganglionic blockade, there was a reduced fall in
      blood pressure in the NOX2 and NOX4 knockdown/knockout mice. Western blot
      analyses of the PVN of siRNA-NOX2- or siRNA-NOX4-injected mice confirmed a marked
      reduction in the expression of NOX2 or NOX4 protein. In cultured PVN neurons,
      silencing either NOX2 or NOX4 protein production by culturing PVN cells with
      siRNA-NOX2 or siRNA-NOX4 attenuated Aldo-induced ROS. These data indicate that
      both NOX2 and NOX4 in the PVN contribute to elevated sympathetic activity and the
      hypertensivogenic actions induced by mineralocorticoid excess.

PMID- 22140042
TI  - Mapping 3-D functional capillary geometry in rat skeletal muscle in vivo.
AB  - We have developed a novel mapping software package to reconstruct microvascular
      networks in three dimensions (3-D) from in vivo video images for use in blood
      flow and O2 transport modeling. An intravital optical imaging system was used to
      collect video sequences of blood flow in microvessels at different depths in the
      tissue. Functional images of vessels were produced from the video sequences and
      were processed using automated edge tracking software to yield location and
      geometry data for construction of the 3-D network. The same video sequences were
      analyzed for hemodynamic and O2 saturation data from individual capillaries in
      the network. Simple user-driven commands allowed the connection of vessel
      segments at bifurcations, and semiautomated registration enabled the tracking of
      vessels across multiple focal planes and fields of view. The reconstructed
      networks can be rotated and manipulated in 3-D to verify vessel connections and
      continuity. Hemodynamic and O2 saturation measurements made in vivo can be
      indexed to corresponding vessels and visualized using colorized maps of the
      vascular geometry. Vessels in each reconstruction are saved as text-based files
      that can be easily imported into flow or O2 transport models with complete
      geometry, hemodynamic, and O2 transport conditions. The results of digital
      morphometric analysis of seven microvascular networks showed mean capillary
      diameters and overall capillary density consistent with previous findings using
      histology and corrosion cast techniques. The described mapping software is a
      valuable tool for the quantification of in vivo microvascular geometry,
      hemodynamics, and oxygenation, thus providing rich data sets for experiment-based
      computational models.

PMID- 22140044
TI  - The heart-specific NH2-terminal extension regulates the molecular conformation
      and function of cardiac troponin I.
AB  - In addition to the core structure conserved in all troponin I isoforms, cardiac
      troponin I (cTnI) has an ~30 amino acids NH(2)-terminal extension. This peptide
      segment is a heart-specific regulatory structure containing two Ser residues that
      are substrates of PKA. Under beta-adrenergic regulation, phosphorylation of cTnI
      in the NH(2)-terminal extension increases the rate of myocardial relaxation. The
      NH(2)-terminal extension of cTnI is also removable by restrictive proteolysis to
      produce functional adaptation to hemodynamic stresses. The molecular mechanism
      for the NH(2)-terminal modifications to regulate the function of cTnI is not
      fully understood. In the present study, we tested a hypothesis that the NH(2)
      terminal extension functions by modulating the conformation of other regions of
      cTnI. Monoclonal antibody epitope analysis and protein binding experiments
      demonstrated that deletion of the NH(2)-terminal segment altered epitopic
      conformation in the middle, but not COOH-terminal, region of cTnI. PKA
      phosphorylation produced similar effects. This targeted long-range conformational
      modulation corresponded to changes in the binding affinities of cTnI for troponin
      T and for troponin C in a Ca(2+)-dependent manner. The data suggest that the
      NH(2)-terminal extension of cTnI regulates cardiac muscle function through
      modulating molecular conformation and function of the core structure of cTnI.

PMID- 22140043
TI  - Magnitude of length-dependent changes in contractile properties varies with titin
      isoform in rat ventricles.
AB  - The effects of differential expression of titin isoforms on sarcomere length (SL)
      dependent changes in passive force, maximum Ca(2+)-activated force, apparent
      cooperativity in activation of force (n(H)), Ca(2+) sensitivity of force
      (pCa(50)), and rate of force redevelopment (k(tr)) were investigated in rat
      cardiac muscle. Skinned right ventricular trabeculae were isolated from wild-type
      (WT) and mutant homozygote (Ho) hearts expressing predominantly a smaller N2B
      isoform (2,970 kDa) and a giant N2BA-G isoform (3,830 kDa), respectively.
      Stretching WT and Ho trabeculae from SL 2.0 to 2.35 MUm increased passive force,
      maximum Ca(2+)-activated force, and pCa(50), and it decreased n(H) and k(tr).
      Compared with WT trabeculae, the magnitude of SL-dependent changes in passive
      force, maximum Ca(2+)-activated force, pCa(50), and n(H) was significantly
      smaller in Ho trabeculae. These results suggests that, at least in rat ventricle,
      the magnitude of SL-dependent changes in passive force, maximum Ca(2+)-activated
      force, pCa(50), n(H), and k(tr) is defined by the titin isoform.

PMID- 22140045
TI  - Adipose stromal vascular fraction cell construct sustains coronary microvascular
      function after acute myocardial infarction.
AB  - A three-dimensional tissue construct was created using adipose-derived stromal
      vascular fraction (SVF) cells and evaluated as a microvascular protection
      treatment in a myocardial infarction (MI) model. This study evaluated coronary
      blood flow (BF) and global left ventricular function after MI with and without
      the SVF construct. Fischer-344 rats were separated into four groups: sham
      operation (sham), MI, MI Vicryl patch (no cells), and MI SVF construct (MI SVF).
      SVF cells were labeled with green fluorescent protein (GFP). Immediately
      postinfarct, constructs were implanted onto the epicardium at the site of
      ischemia. Four weeks postsurgery, the coronary BF reserve was significantly
      decreased by 67% in the MI group and 75% in the MI Vicryl group compared with the
      sham group. The coronary BF reserve of the sham and MI SVF groups in the area at
      risk was not significantly different (sham group: 83 +/- 22% and MI SVF group: 57
      +/- 22%). Griffonia simplicifolia I and GFP-positive SVF immunostaining revealed
      engrafted SVF cells around microvessels in the infarct region 4 wk postimplant.
      Overall heart function, specifically ejection fraction, was significantly greater
      in MI SVF hearts compared with MI and MI Vicryl hearts (MI SVF: 66 +/- 4%, MI: 37
      +/- 8%, and MI Vicryl: 29 +/- 6%). In conclusion, adipose-derived SVF cells can
      be used to construct a novel therapeutic modality for treating microvascular
      instability and ischemia through implantation on the epicardial surface of the
      heart. The SVF construct implanted immediately after MI not only maintains heart
      function but also sustains microvascular perfusion and function in the infarct
      area by sustaining the coronary BF reserve.

PMID- 22140046
TI  - Adaptive response of vascular endothelial cells to an acute increase in shear
      stress magnitude.
AB  - The adaptation of vascular endothelial cells to shear stress alteration induced
      by global hemodynamic changes, such as those accompanying exercise or digestion,
      is an essential component of normal endothelial physiology in vivo. An
      understanding of the transient regulation of endothelial phenotype during
      adaptation to changes in mural shear will advance our understanding of
      endothelial biology and may yield new insights into the mechanism of
      atherogenesis. In this study, we characterized the adaptive response of arterial
      endothelial cells to an acute increase in shear stress magnitude in well-defined
      in vitro settings. Porcine endothelial cells were preconditioned by a basal level
      shear stress of 15 +/- 15 dyn/cm(2) at 1 Hz for 24 h, after which an acute
      increase in shear stress to 30 +/- 15 dyn/cm(2) was applied. Endothelial
      permeability nearly doubled after 40-min exposure to the elevated shear stress
      and then decreased gradually. Transcriptomics studies using microarray techniques
      identified 86 genes that were sensitive to the elevated shear. The acute increase
      in shear stress promoted the expression of a group of anti-inflammatory and
      antioxidative genes. The adaptive response of the global gene expression profile
      is triphasic, consisting of an induction period, an early adaptive response (ca.
      45 min) and a late remodeling response. Our results suggest that endothelial
      cells exhibit a specific phenotype during the adaptive response to changes in
      shear stress; this phenotype is different than that of fully adapted endothelial
      cells.

PMID- 22140048
TI  - Cooperative interaction between reactive oxygen species and Ca2+ signals
      contributes to angiotensin II-induced hypertrophy in adult rat cardiomyocytes.
AB  - Reactive oxygen species (ROS) and Ca(2+) signals are closely associated with the
      pathogenesis of cardiac hypertrophy. However, the cause and effect of the two
      signals in cardiac hypertrophy remain to be clarified. We extend our recent
      report by investigating a potential interaction between ROS and Ca(2+) signals
      utilizing in vitro and in vivo angiotensin II (ANG II)-induced cardiac
      hypertrophy models. ANG II-induced initial Ca(2+) transients mediated by inositol
      trisphosphate (IP(3)) triggered initial ROS production in adult rat
      cardiomyocytes. The ROS generated by activation of the NAD(P)H oxidase complex
      via Rac1 in concert with Ca(2+) activates ADP-ribosyl cyclase to generate cyclic
      ADP-ribose (cADPR). This messenger-mediated Ca(2+) signal further augments ROS
      production, since 2,2'-dihydroxyazobenzene, an ADP-ribosyl cyclase inhibitor, or
      8-Br-cADPR, an antagonistic analog of cADPR, abolished further ROS production.
      Data from short hairpin RNA (shRNA)-mediated knockdown of Akt1 and p47(phox)
      demonstrated that Akt1 is the upstream key molecule responsible for the
      initiation of Ca(2+) signal that activates p47(phox) to generate ROS in
      cardiomyocytes. Nuclear translocation of nuclear factor of activated T-cell in
      cardiomyocytes was significantly suppressed by treatment with NAD(P)H oxidase
      inhibitors as well as by shRNA against Akt1 and p47(phox). Our results suggest
      that in cardiomyocytes Ca(2+) and ROS messengers generated by ANG II amplify the
      initial signals in a cooperative manner, thereby leading to cardiac hypertrophy.

PMID- 22140047
TI  - Activation of endothelial TRPV4 channels mediates flow-induced dilation in human
      coronary arterioles: role of Ca2+ entry and mitochondrial ROS signaling.
AB  - In human coronary arterioles (HCAs) from patients with coronary artery disease,
      flow-induced dilation is mediated by a unique mechanism involving the release of
      H(2)O(2) from the mitochondria of endothelial cells (ECs). How flow activates ECs
      to elicit the mitochondrial release of H(2)O(2) remains unclear. Here, we
      examined the role of the transient receptor potential vanilloid type 4 (TRPV4)
      channel, a mechanosensitive Ca(2+)-permeable cation channel, in mediating ROS
      formation and flow-induced dilation in HCAs. Using RT-PCR, Western blot analysis,
      and immunohistochemical analysis, we detected the mRNA and protein expression of
      TRPV4 channels in ECs of HCAs and cultured human coronary artery ECs (HCAECs). In
      HCAECs, 4alpha-phorbol-12,13-didecanoate (4alpha-PDD), a selective TRPV4 agonist,
      markedly increased (via Ca(2+) influx) intracellular Ca(2+) concentration. In
      isolated HCAs, activation of TRPV4 channels by 4alpha-PDD resulted in a potent
      concentration-dependent dilation, and the dilation was inhibited by removal of
      the endothelium and by catalase, a H(2)O(2)-metabolizing enzyme. Fluorescence ROS
      assays showed that 4alpha-PDD increased the production of mitochondrial
      superoxide in HCAECs. 4alpha-PDD also enhanced the production of H(2)O(2) and
      superoxide in HCAs. Finally, we found that flow-induced dilation of HCAs was
      markedly inhibited by different TRPV4 antagonists and TRPV4-specific small
      interfering RNA. In conclusion, the endothelial TRPV4 channel is critically
      involved in flow-mediated dilation of HCAs. TRPV4-mediated Ca(2+) entry may be an
      important signaling event leading to the flow-induced release of mitochondrial
      ROS in HCAs. Elucidation of this novel TRPV4-ROS pathway may improve our
      understanding of the pathogenesis of coronary artery disease and/or other
      cardiovascular disorders.

PMID- 22140049
TI  - Angiotensin-(1-7) attenuates angiotensin II-induced cardiac remodeling associated
      with upregulation of dual-specificity phosphatase 1.
AB  - Chronic hypertension induces cardiac remodeling, including left ventricular
      hypertrophy and fibrosis, through a combination of both hemodynamic and humoral
      factors. In previous studies, we showed that the heptapeptide ANG-(1-7) prevented
      mitogen-stimulated growth of cardiac myocytes in vitro, through a reduction in
      the activity of the MAPKs ERK1 and ERK2. In this study, saline- or ANG II-infused
      rats were treated with ANG-(1-7) to determine whether the heptapeptide reduces
      myocyte hypertrophy in vivo and to identify the signaling pathways involved in
      the process. ANG II infusion into normotensive rats elevated systolic blood
      pressure >50 mmHg, in association with increased myocyte cross-sectional area,
      ventricular atrial natriuretic peptide mRNA, and ventricular brain natriuretric
      peptide mRNA. Although infusion with ANG-(1-7) had no effect on the ANG II
      stimulated elevation in blood pressure, the heptapeptide hormone significantly
      reduced the ANG II-mediated increase in myocyte cross-sectional area,
      interstitial fibrosis, and natriuretic peptide mRNAs. ANG II increased phospho
      ERK1 and phospho-ERK2, whereas cotreatment with ANG-(1-7) reduced the
      phosphorylation of both MAPKs. Neither ANG II nor ANG-(1-7) altered the ERK1/2
      MAPK kinase MEK1/2. However, ANG-(1-7) infusion, with or without ANG II,
      increased the MAPK phosphatase dual-specificity phosphatase (DUSP)-1; in
      contrast, treatment with ANG II had no effect on DUSP-1, suggesting that ANG-(1
      7) upregulates DUSP-1 to reduce ANG II-stimulated ERK activation. These results
      indicate that ANG-(1-7) attenuates cardiac remodeling associated with a chronic
      elevation in blood pressure and upregulation of a MAPK phosphatase and may be
      cardioprotective in patients with hypertension.

PMID- 22140050
TI  - Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose
      vasoconstriction of mouse mesenteric arteries.
AB  - It is generally accepted that the endothelium regulates vascular tone independent
      of the activity of the sympathetic nervous system. Here, we tested the hypothesis
      that the activation of sympathetic nerves engages the endothelium to oppose
      vasoconstriction. Local inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+)
      signals ("pulsars") in or near endothelial projections to vascular smooth muscle
      (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical
      field stimulation of sympathetic nerves induced an increase in endothelial cell
      (EC) Ca(2+) pulsars, recruiting new pulsar sites without affecting activity at
      existing sites. This increase in Ca(2+) pulsars was blocked by bath application
      of the alpha-adrenergic receptor antagonist prazosin or by TTX but was unaffected
      by directly picospritzing the alpha-adrenergic receptor agonist phenylephrine
      onto the vascular endothelium, indicating that nerve-derived norepinephrine acted
      through alpha-adrenergic receptors on smooth muscle cells. Moreover, EC Ca(2+)
      signaling was not blocked by inhibitors of purinergic receptors, ryanodine
      receptors, or voltage-dependent Ca(2+) channels, suggesting a role for IP(3),
      rather than Ca(2+), in VSM-to-endothelium communication. Block of intermediate
      conductance Ca(2+)-sensitive K(+) channels, which have been shown to colocalize
      with IP(3) receptors in endothelial projections to VSM, enhanced nerve-evoked
      constriction. Collectively, our results support the concept of a transcellular
      negative feedback module whereby sympathetic nerve stimulation elevates EC Ca(2+)
      signals to oppose vasoconstriction.

PMID- 22140051
TI  - Secondhand tobacco smoke, arterial stiffness, and altered circadian blood
      pressure patterns are associated with lung inflammation and oxidative stress in
      rats.
AB  - Chronic smoking and secondhand tobacco smoke exposure are major risk factors for
      cardiovascular disease that are known to adversely alter the structural and
      mechanical properties of arteries. The objective of this study was to determine
      the effects of subchronic secondhand tobacco smoke exposure on circadian blood
      pressure patterns, arterial stiffness, and possible sources of oxidative stress
      in conscious, unsedated radiotelemetry-implanted rats. Pulse wave change in
      pressure over time (dP/dt) was used an indicator of arterial stiffness and was
      compared with both structural (wall thickness) and functional (nitric oxide
      production and bioactivity and endothelin-1 levels) features of the arterial
      wall. In addition, histology of lung, heart, and liver was examined as well as
      pulmonary and hepatic detoxifying enzyme activity (cytochrome P450, specifically
      CYP1A1). Subchronic secondhand tobacco smoke exposure altered the circadian
      pattern of heart rate and blood pressure, with a loss in the normal dipping
      pattern of blood pressure during sleep. Secondhand tobacco smoke exposure also
      increased pulse wave dP/dt in the absence of any structural modifications in the
      arterial wall. Furthermore, although nitric oxide production and endothelin-1
      levels were not altered by secondhand tobacco smoke, there was increased
      inactivation of nitric oxide as indicated by peroxynitrite production. Increased
      lung neutrophils or pulmonary CYP1A1 may be responsible for the increase in
      oxidative stress in rats exposed to secondhand tobacco smoke. In turn, this may
      be related to the observed failure of blood pressure to dip during periods of
      sleep and a possible increase in arterial stiffness.

PMID- 22140052
TI  - Reduced mitochondrial Ca2+ loading and improved functional recovery after
      ischemia-reperfusion injury in old vs. young guinea pig hearts.
AB  - Oxidative damage and impaired cytosolic Ca(2+) concentration ([Ca(2+)](cyto))
      handling are associated with mitochondrial [Ca(2+)] ([Ca(2+)](mito)) overload and
      depressed functional recovery after cardiac ischemia-reperfusion (I/R) injury. We
      hypothesized that hearts from old guinea pigs would demonstrate impaired
      [Ca(2+)](mito) handling, poor functional recovery, and a more oxidized state
      after I/R injury compared with hearts from young guinea pigs. Hearts from young
      (~4 wk) and old (>52 wk) guinea pigs were isolated and perfused with Krebs-Ringer
      solution (2.1 mM Ca(2+) concentration at 37 degrees C). Left ventricular pressure
      (LVP, mmHg) was measured with a balloon, and NADH, [Ca(2+)](mito) (nM), and
      [Ca(2+)](cyto) (nM) were measured by fluorescence with a fiber optic probe placed
      against the left ventricular free wall. After baseline (BL) measurements, hearts
      were subjected to 30 min global ischemia and 120 min reperfusion (REP). In old
      vs. young hearts we found: 1) percent infarct size was lower (27 +/- 9 vs. 57 +/-
      2); 2) developed LVP (systolic-diastolic) was higher at 10 min (57 +/- 11 vs. 29
      +/- 2) and 60 min (55 +/- 10 vs. 32 +/- 2) REP; 3) diastolic LVP was lower at 10
      and 60 min REP (6 +/- 3 vs. 29 +/- 4 and 3 +/- 3 vs. 21 +/- 4 mmHg); 4) mean
      [Ca(2+)](cyto) was higher during ischemia (837 +/- 39 vs. 541 +/- 39), but
      [Ca(2+)](mito) was lower (545 +/- 62 vs. 975 +/- 38); 5) [Ca(2+)](mito) was lower
      at 10 and 60 min REP (129 +/- 2 vs. 293 +/- 23 and 122 +/- 2 vs. 234 +/- 15); 6)
      reduced inotropic responses to dopamine and digoxin; and 7) NADH was elevated
      during ischemia in both groups and lower than BL during REP. Contrary to our
      stated hypotheses, old hearts showed reduced [Ca(2+)](mito), decreased
      infarction, and improved basal mechanical function after I/R injury compared with
      young hearts; no differences were noted in redox state due to age. In this model,
      aging-associated protection may be linked to limited [Ca(2+)](mito) loading after
      I/R injury despite higher [Ca(2+)](cyto) load during ischemia in old vs. young
      hearts.

PMID- 22140053
TI  - Reconstruction of inferior right hepatic veins in living donor liver
      transplantation using right liver grafts.
AB  - Because revascularization of the inferior right hepatic vein (IRHV) is a major
      component of right liver graft (RLG) reconstruction, we assessed the surgical
      techniques and clinical outcomes of IRHV reconstruction so that we could
      formulate practical guidelines for standardized procedures. From July 2004 to
      February 2010, we performed separate IRHV reconstructions in 487 of 1142 adult
      RLG recipients (42.7%). These recipients included 364 patients with a natural
      single IRHV and 123 patients with multiple IRHVs; in the latter group, the IRHVs
      were unified by venoplasty, which enabled a single anastomosis. The 1-year
      stenosis rates for the single-vein and venoplasty groups were 23% and 18.9%,
      respectively, and the early stent insertion rates were 7.1% and 9.8%,
      respectively (P = 0.09). Late IRHV occlusion did not lead to graft dysfunction,
      and all large major IRHVs were patent. A morphometric analysis showed that IRHV
      stenosis was associated with IRHV stretching and an anastomotic level
      discrepancy. This led to refinements of the surgical techniques: IRHV orifices
      were shaped into funnels, and the IRHV anastomosis was accurately placed at the
      recipient inferior vena cava (IVC). In an ongoing prospective study of 35
      patients, our funneling unification venoplasty resulted in only 1 episode (2.9%)
      of early IRHV stenosis requiring stenting at a median follow-up of 8 months. The
      final configurations of the reconstructed IRHVs after funneling unification
      venoplasty and extensive IVC dissection were very similar to those of the native
      donor liver. In conclusion, we suggest that in combination with extensive
      recipient IVC dissection, funneling and unification venoplasty techniques are
      useful for securely reconstructing single or multiple IRHVs during the
      implantation of RLGs.

PMID- 22140054
TI  - Long-term neuroimaging follow-up on an asymptomatic juvenile metachromatic
      leukodystrophy patient after hematopoietic stem cell transplantation: evidence of
      myelin recovery and ongoing brain maturation.

PMID- 22140055
TI  - Predictive event modelling in multicenter clinical trials with waiting time to
      response.
AB  - A new analytic statistical technique for predictive event modeling in ongoing
      multicenter clinical trials with waiting time to response is developed. It allows
      for the predictive mean and predictive bounds for the number of events to be
      constructed over time, accounting for the newly recruited patients and patients
      already at risk in the trial, and for different recruitment scenarios. For
      modeling patient recruitment, an advanced Poisson-gamma model is used, which
      accounts for the variation in recruitment over time, the variation in recruitment
      rates between different centers and the opening or closing of some centers in the
      future. A few models for event appearance allowing for 'recurrence', 'death' and
      'lost-to-follow-up' events and using finite Markov chains in continuous time are
      considered. To predict the number of future events over time for an ongoing trial
      at some interim time, the parameters of the recruitment and event models are
      estimated using current data and then the predictive recruitment rates in each
      center are adjusted using individual data and Bayesian re-estimation. For a
      typical scenario (continue to recruit during some time interval, then stop
      recruitment and wait until a particular number of events happens), the closed
      form expressions for the predictive mean and predictive bounds of the number of
      events at any future time point are derived under the assumptions of Markovian
      behavior of the event progression. The technique is efficiently applied to
      modeling different scenarios for some ongoing oncology trials. Case studies are
      considered.

PMID- 22140056
TI  - Repeated transplantation of hepatocytes prevents fulminant hepatitis in a rat
      model of Wilson's disease.
AB  - The outcome of consecutive hepatocyte transplants was explored in a rat model of
      Wilson's disease before the onset of fulminant hepatitis without preconditioning
      regimens. Rats received a high-copper diet in order to induce a rapid induction
      of liver failure. Sham-operated rats (15/15) developed jaundice and fulminant
      hepatitis, and they died within 4 weeks of first transplantation. Despite the
      continuation of a high dietary copper challenge, long-term survival was observed
      for a notable proportion of the transplanted animals (7/18). All survivors
      displayed normalized levels of hepatitis-associated serum markers and
      ceruloplasmin oxidase activity by posttransplant days 50 and 98, respectively.
      The liver copper concentrations, the liver histology, and the expression of
      marker genes were significantly restored within 4 months of transplantation in
      comparison with the control group. The high expression of a copper transporter
      gene (ATPase Cu++ transporting beta polypeptide) in the livers of the survivors
      indicated a high rate of repopulation by donor hepatocytes. Our data suggest that
      repeated cell transplantation can overcome the limitations of a single therapy
      session in rats with severe hepatic disease by functionally restoring the host
      liver without preconditioning.

PMID- 22140057
TI  - Mild nasal malformations and parietal foramina caused by homozygous ALX4
      mutations.
AB  - We report on a boy born to consanguineous parents, who had hypertelorism, a broad
      nasal bridge, ridge and tip, bifid nasal tip, cleft alae nasi, broad columella,
      unilateral preauricular tag, shallow labiogingival sulcus, and bilateral large
      parietal foramina. Cranial MRI revealed a kinked corpus body and small cerebellar
      vermis. Molecular analysis uncovered a homozygous c.673C > G (p.Q225E) mutation
      in ALX4 gene. We compare the relatively mild phenotype in the patient to the more
      marked phenotype described in other patients with homozygous ALX4 mutations, and
      to the phenotypes in patients with mutations in other ALX genes.

PMID- 22140058
TI  - An assessment of the statistical methods used to analyse toxicology studies.
AB  - The Statisticians in the Pharmaceutical Industry Toxicology Special Interest
      Group has collated and compared statistical analysis methods for a number of
      toxicology study types including general toxicology, genetic toxicology, safety
      pharmacology and carcinogenicity. In this paper, we present the study design,
      experimental units and analysis methods.

PMID- 22140059
TI  - Doppler echocardiographic evaluation of prosthetic valve function.

PMID- 22140060
TI  - Three dimensional echocardiography in congenital heart disease.

PMID- 22140061
TI  - Retraction. Assessment of vascular phenotype using a novel very high resolution
      ultrasound technique in adolescents after aortic coarctation repair and/or stent
      implantation: relationship to central haemodynamics and left ventricular mass.

PMID- 22140064
TI  - A family of pseudohypoparathyroidism type Ia with an 850-kb submicroscopic
      deletion encompassing the whole GNAS locus.

PMID- 22140063
TI  - Cell therapies for liver diseases.
AB  - Cell therapies, which include bioartificial liver support and hepatocyte
      transplantation, have emerged as potential treatments for a variety of liver
      diseases. Acute liver failure, acute-on-chronic liver failure, and inherited
      metabolic liver diseases are examples of liver diseases that have been
      successfully treated with cell therapies at centers around the world. Cell
      therapies also have the potential to be widely applied to other liver diseases,
      including noninherited liver diseases and liver cancer, and to improve the
      success of liver transplantation. Here we briefly summarize current concepts of
      cell therapy for liver diseases.

PMID- 22140066
TI  - Subgroup analyses of clinical effectiveness to support health technology
      assessments.
AB  - Subgroup analysis is an integral part of access and reimbursement dossiers, in
      particular health technology assessment (HTA), and their HTA recommendations are
      often limited to subpopulations. HTA recommendations for subpopulations are not
      always clear and without controversies. In this paper, we review several HTA
      guidelines regarding subgroup analyses. We describe good statistical principles
      for subgroup analyses of clinical effectiveness to support HTAs and include case
      examples where HTA recommendations were given to subpopulations only. Unlike
      regulatory submissions, pharmaceutical statisticians in most companies have had
      limited involvement in the planning, design and preparation of HTA/payers
      submissions. We hope to change this by highlighting how pharmaceutical
      statisticians should contribute to payers' submissions. This includes early
      engagement in reimbursement strategy discussions to influence the design,
      analysis and interpretation of phase III randomized clinical trials as well as
      meta-analyses/network meta-analyses. The focus on this paper is on subgroup
      analyses relating to clinical effectiveness as we believe this is the first key
      step of statistical involvement and influence in the preparation of HTA and
      reimbursement submissions.

PMID- 22140065
TI  - Potential role of Hsp25 in calcium-modulated cardiomyocytes.
AB  - Cardiac muscle contraction is initiated by the entry of Ca2+ ions from the
      extracellular spaces and the Ca2+ stores in the sarcoplasmic reticulum into the
      myoplasm. Calcium signaling is the most important factor in cardiac cell
      homeostasis. In this study, we investigated the effect of caffeine, an inducer of
      intracellular Ca2+ accumulation, on HL-1 cardiomyocytes by using a proteomic
      approach. Following the separation of the cell lysates and visualization of the
      protein spots using two-dimensional gel electrophoresis and silver staining,
      respectively, we identified 24 differentially expressed protein spots in the
      caffeine-treated group as compared with the controls by using MALDI-TOF/TOF MS.
      Of these 24 spots, 8 proteins were up-regulated and 16 proteins were down
      regulated. These differentially expressed proteins are predominantly involved in
      cellular metabolism, cellular organization, and ion/protein transport.
      Furthermore, we found that Hsp25, one of the differentially expressed proteins,
      is modified by caffeine treatment. Depletion of Hsp25 transcripts by siRNA
      increased caffeine-mediated signaling, including ERK activation, and decreased
      the Ca2+ transient peak and expression of calsequestrin 2 in HL-1 cardiomyocytes.
      These results suggest that proteins having various functions are involved in the
      regulation of Ca2+ homeostasis, and that Hsp25 plays an important role in
      regulating cardiac function during caffeine response.

PMID- 22140067
TI  - Cumulative risk of cardiovascular events after orthotopic liver transplantation.
AB  - As survival after orthotopic liver transplantation (OLT) improves, cardiovascular
      (CV) disease has emerged as the leading cause of non-graft-related deaths. The
      aims of our study were to determine the cumulative risk of CV events after OLT
      and to analyze predictive risk factors for those experiencing a CV event after
      OLT. We identified all adult patients who underwent OLT at our institution for
      end-stage liver disease between October 1996 and July 2008. The cumulative risk
      of CV events after OLT was analyzed with the Kaplan-Meier method. Multivariate
      logistic regression analysis was used to identify factors independently
      associated with CV events after OLT. In all, 775 patients were included in our
      study cohort (mean age of 53.3 years, female proportion = 44%, Caucasian
      proportion = 84%, median follow-up = 40 months). The most common indications for
      OLT were hepatitis C virus (33.2%), alcohol (14.5%), and cryptogenic cirrhosis
      (12.7%). Eighty-three patients suffered 1 or more CV events after OLT.
      Posttransplant metabolic syndrome was more prevalent in patients with CV events
      versus patients with no CV events (61.4% versus 34.1%, P < 0.001). According to a
      multivariate analysis, independent predictors of CV events were an older age at
      transplantation [odds ratio (OR) = 1.2, addition of 95% confidence interval (CI)
      = 1.1-1.3, P = 0.006], male sex (OR = 2.0, 95% CI = 1.2-3.3, P = 0.01),
      posttransplant diabetes (OR = 2.0, 95% CI = 1.3-3.3, P = 0.003), posttransplant
      hypertension (OR = 1.8, 95% CI = 1.1-3.0, P = 0.02), and mycophenolate mofetil
      (OR = 2.0, 95% CI = 1.3-3.2, P = 0.003). Among post-OLT patients, the cumulative
      risk at 5 years of 13.5%, respectively. In conclusion, cardiac complications
      after liver transplantation are common (Approximately 10% of patients experience
      1 or move cv events). Patients with posttransplant hypertension and diabetes,
      which are modifiable risk factors, are approximately twice as likely to
      experience a CV event.

PMID- 22140068
TI  - Editorial comment: New diagnostic criteria for Marfan syndrome.

PMID- 22140069
TI  - Analysis of the urine proteome via a combination of multi-dimensional approaches.
AB  - Urine is a biological fluid that is non-invasively and easily harvested, and
      exhibits high stability from the proteomics point of view. At the downside, the
      overall low protein content of urine as well as the presence of low- and high
      abundance proteins underscores the need for protein enrichment. As a continuation
      of previous efforts towards the comprehensive characterization of the urine
      proteome, the current study targeted the mining of urine proteins through the
      combined application of different protein separation methodologies, specifically,
      liquid chromatography and preparative electrophoresis along with 1D gel
      electrophoresis and protein identification by mass spectrometry. In order to
      enhance comparison and integration of different experimental data sets, the
      "standard" urine sample developed within the European Kidney and Urine Proteomics
      (EuroKUP) COST Action, was employed. As a contribution to the existing knowledge,
      we focused on maintaining and providing information about experimental mass of
      the identified proteins as well as information pertaining to their relative
      abundance--as allowed by technical limitations--thus providing an initial view of
      different isoforms representation and facilitating their future characterization.
      The difficulties in comparing proteome mining data sets become once more evident,
      underscoring the need for adopting standardized ways for data reporting as well
      as for potential new approaches for data analysis involving a thorough
      investigation of received information at the peptide level.

PMID- 22140070
TI  - Activation of calpains mediates early lung neutrophilic inflammation in
      ventilator-induced lung injury.
AB  - Lung inflammatory responses in the absence of infection are considered to be one
      of primary mechanisms of ventilator-induced lung injury. Here, we determined the
      role of calpain in the pathogenesis of lung inflammation attributable to
      mechanical ventilation. Male C57BL/6J mice were subjected to high (28 ml/kg)
      tidal volume ventilation for 2 h in the absence and presence of calpain inhibitor
      I (10 mg/kg). To address the isoform-specific functions of calpain 1 and calpain
      2 during mechanical ventilation, we utilized a liposome-based delivery system to
      introduce small interfering RNAs targeting each isoform in pulmonary vasculature
      in vivo. Mechanical ventilation with high tidal volume induced rapid (within
      minutes) and persistent calpain activation and lung inflammation as evidenced by
      neutrophil recruitment, production of TNF-alpha and IL-6, pulmonary vascular
      hyperpermeability, and lung edema formation. Pharmaceutical calpain inhibition
      significantly attenuated these inflammatory responses caused by lung
      hyperinflation. Depletion of calpain 1 or calpain 2 had a protective effect
      against ventilator-induced lung inflammatory responses. Inhibition of calpain
      activity by means of siRNA silencing or pharmacological inhibition also reduced
      endothelial nitric oxide (NO) synthase (NOS-3)-mediated NO production and
      subsequent ICAM-1 phosphorylation following high tidal volume ventilation. These
      results suggest that calpain activation mediates early lung inflammation during
      ventilator-induced lung injury via NOS-3/NO-dependent ICAM-1 phosphorylation and
      neutrophil recruitment. Inhibition of calpain activation may therefore provide a
      novel and promising strategy for the prevention and treatment of ventilator
      induced lung injury.

PMID- 22140071
TI  - GM-CSF provides autocrine protection for murine alveolar epithelial cells from
      oxidant-induced mitochondrial injury.
AB  - Exposure of mice to hyperoxia induces alveolar epithelial cell (AEC) injury,
      acute lung injury and death. Overexpression of granulocyte-macrophage colony
      stimulating factor (GM-CSF) in the lung protects against these effects, although
      the mechanisms are not yet clear. Hyperoxia induces cellular injury via effects
      on mitochondrial integrity, associated with induction of proapoptotic members of
      the Bcl-2 family. We hypothesized that GM-CSF protects AEC through effects on
      mitochondrial integrity. MLE-12 cells (a murine type II cell line) and primary
      murine type II AEC were subjected to oxidative stress by exposure to 80% oxygen
      and by exposure to H(2)O(2). Exposure to H(2)O(2) induced cytochrome c release
      and decreased mitochondrial reductase activity in MLE-12 cells. Incubation with
      GM-CSF significantly attenuated these effects. Protection induced by GM-CSF was
      associated with Akt activation. GM-CSF treatment also resulted in increased
      expression of the antiapoptotic Bcl-2 family member, Mcl-1. Primary murine AEC
      were significantly more tolerant of oxidative stress than MLE-12 cells. In
      contrast to MLE-12 cells, primary AEC expressed significant GM-CSF at baseline
      and demonstrated constitutive activation of Akt and increased baseline expression
      of Mcl-1. Treatment with exogenous GM-CSF further increased Akt activation and
      Mcl-1 expression in primary AEC. Conversely, suppression of AEC GM-CSF expression
      by use of GM-CSF-specific small interfering RNA resulted in decreased tolerance
      of oxidative stress, Furthermore, silencing of Mcl-1 prevented GM-CSF-induced
      protection. We conclude that GM-CSF protects alveolar epithelial cells against
      oxidative stress-induced mitochondrial injury via the Akt pathway and its
      downstream components, including Mcl-1. Epithelial cell-derived GM-CSF may
      contribute to intrinsic defense mechanisms limiting lung injury.

PMID- 22140073
TI  - Using genomics for birth defects epidemiology: can epigenetics cut the GxE
      Gordian knot?
AB  - Most birth defects are etiologically complex disorders caused by combinations of
      genetic and environmental factors, but most studies of birth defect etiology have
      examined only genetic factors or only environmental factors and have not
      considered interactions among them. Genome-wide epigenetic studies, which use the
      same genomic technologies that have revolutionized our ability to identify
      genetic causes of disease, provide an attractive way to study gene-environment
      interactions. However, finding an association between epigenetic variation and an
      etiologically complex birth defect without knowledge of the genetic variation and
      environmental exposures affecting the individuals who were studied usually
      provides little or no information regarding the cause of the disorder. In order
      for genome-wide studies of epigenetic variation to contribute to our
      understanding of the causes of birth defects, these studies must be combined with
      studies of environmental exposures and studies of genetic variation in the same
      subjects. Under such circumstances, epigenetic studies may help to establish the
      molecular basis for gene-environment interactions.

PMID- 22140072
TI  - Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by
      coordinate expression of components of the fibrinolytic system.
AB  - Alveolar type II (ATII) cell apoptosis and depressed fibrinolysis that promotes
      alveolar fibrin deposition are associated with acute lung injury (ALI) and the
      development of pulmonary fibrosis (PF). We therefore sought to determine whether
      p53-mediated inhibition of urokinase-type plasminogen activator (uPA) and
      induction of plasminogen activator inhibitor-1 (PAI-1) contribute to ATII cell
      apoptosis that precedes the development of PF. We also sought to determine
      whether caveolin-1 scaffolding domain peptide (CSP) reverses these changes to
      protect against ALI and PF. Tissues as well as isolated ATII cells from the lungs
      of wild-type (WT) mice with BLM injury show increased apoptosis, p53, and PAI-1,
      and reciprocal suppression of uPA and uPA receptor (uPAR) protein expression.
      Treatment of WT mice with CSP reverses these effects and protects ATII cells
      against bleomycin (BLM)-induced apoptosis whereas CSP fails to attenuate ATII
      cell apoptosis or decrease p53 or PAI-1 in uPA-deficient mice. These mice
      demonstrate more severe PF. Thus p53 is increased and inhibits expression of uPA
      and uPAR while increasing PAI-1, changes that promote ATII cell apoptosis in mice
      with BLM-induced ALI. We show that CSP, an intervention targeting this pathway,
      protects the lung epithelium from apoptosis and prevents PF in BLM-induced lung
      injury via uPA-mediated inhibition of p53 and PAI-1.

PMID- 22140074
TI  - Diagnostic and therapeutic challenges in pediatric primary sclerosing
      cholangitis.
AB  - Sclerosing cholangitis, an uncommon disorder in children, is progressive and is,
      therefore, an important indication for pediatric liver transplantation. This
      review summarizes current challenges in the diagnosis and treatment of this rare
      form of pediatric liver disease.

PMID- 22140075
TI  - Myelodysplastic syndrome in a child with 15q24 deletion syndrome.
AB  - 15q24 deletion syndrome is a recently-described chromosomal disorder,
      characterized by developmental delay, growth deficiency, distinct facial
      features, digital abnormalities, loose connective tissue, and genital
      malformations in males. To date, 19 patients have been reported. We report on a
      13-year-old boy with this syndrome manifesting childhood myelodysplastic syndrome
      (MDS). He had characteristic facial features, hypospadias, and mild developmental
      delay. He showed neutropenia and thrombocytopenia for several years. At age 13
      years, bone marrow examination was performed, which showed a sign suggestive of
      childhood MDS: mild dysplasia in the myeloid, erythroid, and megakaryocytic cell
      lineages. Array comparative genomic hybridization (array CGH) revealed a de novo
      3.4 Mb 15q24.1q24.3 deletion. Although MDS has not been described in patients
      with the syndrome, a boy was reported to have acute lymphoblastic leukemia (ALL).
      The development of MDS and hematological malignancy in the syndrome might be
      caused by the haploinsufficiency of deleted 15q24 segment either alone or in
      combination with other genetic abnormalities in hematopoietic cells. Further
      hematological investigation is recommended to be beneficial if physical and
      hematological examination results are suggestive of hematopoietic disturbance in
      patients with the syndrome.

PMID- 22140076
TI  - The proteomic study on cellular responses of the testes of zebrafish (Danio
      rerio) exposed to microcystin-RR.
AB  - Microcystin-RR (MC-RR) is a commonly encountered cyanotoxin and receives
      increasing attention due to the risk of its bioaccumulation in aquatic animals
      like fish. This study investigated the protein profiles of zebrafish (Danio
      rerio) testes after intraperitoneal injection (i.p.) with 0.5 LD(50) (2000
      MUg/kg). MC-RR caused a noticeable damage to testicular ultrastructure, showing
      widened intercellular junction, distention of mitochondria. The testes showed a
      rapid response of its defense systems to the oxidative stress caused by MC-RR.
      This is the first to use a proteomic approach to obtain an overview of the
      effects of MC-RR on the testes of zebrafish. The proteomic results revealed that
      toxin exposure remarkably altered the abundance of 24 proteins that were involved
      in cytoskeleton assembly, oxidative stress, glycolysis metabolism, calcium ion
      binding and other biological functions. In conclusion, MC-RR damaged the testes
      and was toxic to the reproductive system of male zebrafish mainly through causing
      oxidative stress.

PMID- 22140077
TI  - Earthquake distresses reproductive function but not fetal development in rats.
AB  - BACKGROUND: It is well known that earthquake severely threatens life-safety and
      physical damage. However, the empirical literature on the effects of nature
      disasters such as earthquake on the reproductive outcomes is limited. METHODS: On
      May 12th, 2008, a massive 8.0 magnitude earthquake occurred in Wenchuan, a city
      92 km away from our animal facility [National Chengdu Center for Safety
      Evaluation of Drugs (NCCSED)]. To investigate whether this tremendous earthquake
      exerted adverse effects on the reproductive and developmental functions in
      Sprague-Dawley rats, we collected some relevant data from reproductive toxicity
      studies around the earthquake, and compared them with the background data, which
      were gathered before and after the earthquake. Copulation ratio, gestation ratio,
      and fertility of female rats, as well as uterine and fetal morphology, were
      examined. RESULTS: Our data demonstrated that the Wenchuan earthquake
      significantly decreased the copulation and gestation ratio, although it did not
      exhibit obvious side effects on some other reproductive and developmental
      parameters.

PMID- 22140078
TI  - Abnormal facial appearance, body asymmetry, limb deformities, and internal
      malformations.
AB  - We describe a newborn girl with multiple congenital anomalies and abnormal
      phenotype comprising underdeveloped corpus callosum with ventriculomegaly,
      chorioretinal atrophy, pulmonary arterial hypertension, annular pancreas,
      horseshoe kidney, asymmetric limb and chest anomalies, spinal segmentation
      defects, hypertrichosis, and unusual face with large anterior fontanel, high
      anterior hairline, broad forehead, mildly underdeveloped midface, hypertelorism,
      depressed nasal bridge, short and upturned nose, large mouth, retrognathia, and
      large and malformed ears. Work-up included cytogenetic studies of lymphocytes and
      skin fibroblasts, subtelomere Multiplex Ligation-dependent Probe Amplification
      (MLPA), whole-genome oligo-array, and molecular analysis of SETBP1 and NSDHL: no
      abnormalities were found. Mucopolysaccharide urinary excretion was elevated.
      Results of metabolic studies for sterol and peroxisomal abnormalities in
      fibroblasts were normal. Additional electronic microscopy studies in skin
      fibroblasts did not show evidence for storage in fibroblasts or lysosomal
      changes. Nosologic considerations allowed exclusion of Schinzel-Giedion and
      Urioste syndrome. This condition seems not to have been described before; a
      segregating Mendelian mutation is assumed.

PMID- 22140079
TI  - Comparative hepatic proteome analysis between lean and obese rats fed a high-fat
      diet reveals the existence of gender differences.
AB  - Gender differences in obesity stem from metabolic and hormonal differences
      between sexes and contribute to differences between women and men in health risks
      attributable to obesity. We hypothesized that liver may be an ideal target for
      the evaluation of gender differences in obesity development in response to a high
      fat diet (HFD). Therefore, to test this hypothesis, we performed a global
      proteome analysis in the liver of lean and obese rats of both genders who were
      fed an HFD through 2-DE combined with MALDI-TOF-MS. When rats were exposed to
      HFD, male rats gained more body weight with increased values of plasma
      biochemical parameters than female rats. Image analysis and further statistical
      analysis of a 2-DE protein map allowed for the detection and identification of 34
      proteins that were significantly modulated in a gender-dependent manner. We found
      19 proteins showing identical gender-different regulation in both normal diet
      (ND) and HFD. Five proteins also showed clear gender differences in both ND and
      HFD; however, their regulation modes in HFD were opposite to those in ND. Of
      particular interest, 10 proteins showed gender differences only in either ND or
      HFD rats. Present proteomic insight into gender-dimorphic protein modulation in
      liver would aid in the improvement of gender awareness in the health-care system
      and in implementation of evidence-based gender-specific clinical recommendations.

PMID- 22140080
TI  - Prenatal epoxiconazole exposure effects on rat postnatal development.
AB  - Although some studies have pointed out to embryo/fetal toxicity, knowledge about
      the potential toxicity of the fungicide epoxiconazole is still limited. Once the
      results of these previous studies have raised some concern, this study studied
      the effects of epoxiconazole maternal exposure on the physical endpoints in the
      development of rat pups. To accomplish that, the effects of epoxiconazole (50.0,
      100.0, and 150.0  mg/kg) were examined when rats were exposed at two different
      developmental stages: during the first 6 days of pregnancy or in the
      organogenesis period (6-15 days). After parturition, pups were tested for growth
      and maturational milestones. Maternal exposure to the fungicide, independently of
      phase, resulted in significantly early mean time to vaginal opening and delayed
      time to testes descent in pups. Weight gain rate in pups and their mothers was
      not affected for the tested exposure period. The findings of this study emphasize
      that epoxiconazole maternal exposure may lead to alterations in developmental
      patterns in nursing pups, consistent with the known influence of epoxiconazole on
      steroid hormone synthesis.

PMID- 22140081
TI  - Report of a mother and daughter with the 12q14 microdeletion syndrome.
AB  - The 12q14 microdeletion syndrome is characterized by microcephaly, short stature,
      osteopoikilosis, weight deficiency, and learning disabilities. We report on a
      mother and daughter with a 12q14 microdeletion. To our knowledge these are the
      first reported familial cases with the syndrome. We also discuss the genes in the
      deleted area that may be contributing to the phenotype.

PMID- 22140085
TI  - Effect of fiber alignment in electrospun scaffolds on keratocytes and corneal
      epithelial cells behavior.
AB  - The contribution of fiber alignment of scaffold on cellular mechanisms was
      evaluated by a comparative study of two different cells sourced from cornea.
      Electrospun scaffolds with similar composition and comparable fiber size were
      fabricated into randomly oriented and aligned scaffolds, which bear paralleled
      degradation of gelatin. Tensile test of wet scaffolds indicated that fiber
      alignment could influence its mechanical properties. Due to the unidirectional
      fiber orientation, aligned scaffold exhibited higher tensile modulus, higher
      break strength, and lower elongation at break than randomly oriented scaffold.
      The effect of fiber alignment on cells behavior was evaluated by cell morphology,
      specific protein expression, adhesion, and proliferation. Different corneal cells
      responded uniquely to fiber alignment of scaffold, keratocytes interacting more
      favorably on alignment scaffold and corneal epithelial cells more favorably on
      randomly oriented scaffold. These results confirmed that fiber alignment of
      scaffold would be benefit for cell proliferation if its contact guidance
      coincided with the cell shape and cytoskeletal tension. This finding is important
      to envisage an advanced composite scaffold that incorporates randomly oriented
      and aligned fibers for the growth and control of different cell types required
      for the successful development of corneal grafts by tissue engineering.

PMID- 22140086
TI  - Does the 1.5 Mb microduplication in chromosome band Xp22.31 have a pathogenetic
      role? New contribution and a review of the literature.

PMID- 22140087
TI  - A synthetic lipid A mimetic modulates human TLR4 activity.

PMID- 22140089
TI  - "Did you find that out in time?": new life trajectories of parents who choose to
      continue a pregnancy where a genetic disorder is diagnosed or likely.
AB  - The availability of tests to detect genetic conditions prenatally has expanded
      considerably in recent decades. These advances allow women and couples choices;
      the choice of whether or not to undergo prenatal screening or diagnosis and
      therefore the choice whether to continue or terminate a pregnancy. Following
      prenatal testing many people choose to terminate an affected pregnancy, however
      little is known about the experiences of parents who choose to continue such a
      pregnancy. This exploratory qualitative study involved in-depth interviews with
      five mothers and four fathers who experienced a pregnancy where a genetic
      diagnosis was, or could have been, detected prenatally. Transcripts of the
      interviews were analyzed using thematic analysis. While the participants'
      experiences of genetic diagnoses and prenatal choices varied, findings revealed
      three major categories triggering new life trajectories for all of these parents:
      knowledge of reproductive risk and receiving a genetic diagnosis; adapting to
      diagnosis and new life path; and attitudes to prenatal diagnosis and disability.
      Parents reported that while dealing with their own attitudes and getting on with
      their "new world," positive and negative attitudes of others impacted on these
      parents' experiences. A conceptual model arising from the major themes is offered
      as a way of thinking about this paradigm. Parents who continue a pregnancy where
      a genetic condition is detected or suspected prenatally, can be supported
      appropriately by health professionals while adjusting to their new life path.

PMID- 22140088
TI  - Consensus recommendations for current treatments and accelerating clinical trials
      for patients with neurofibromatosis type 2.
AB  - Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome characterized by
      bilateral vestibular schwannomas (VS) which often result in deafness despite
      aggressive management. Meningiomas, ependymomas, and other cranial nerve and
      peripheral schwannomas are also commonly found in NF2 and collectively lead to
      major neurologic morbidity and mortality. Traditionally, the overall survival
      rate in patients with NF2 is estimated to be 38% at 20 years from diagnosis.
      Hence, there is a desperate need for new, effective therapies. Recent progress in
      understanding the molecular basis of NF2 related tumors has aided in the
      identification of potential therapeutic targets and emerging clinical therapies.
      In June 2010, representatives of the international NF2 research and clinical
      community convened under the leadership of Drs. D. Gareth Evans (University of
      Manchester) and Marco Giovannini (House Research Institute) to review the state
      of NF2 treatment and clinical trials. This manuscript summarizes the expert
      opinions about current treatments for NF2 associated tumors and recommendations
      for advancing therapies emerging from that meeting. The development of effective
      therapies for NF2 associated tumors has the potential for significant clinical
      advancement not only for patients with NF2 but for thousands of neuro-oncology
      patients afflicted with these tumors.

PMID- 22140090
TI  - Identification of a chronic obstructive pulmonary disease genetic determinant
      that regulates HHIP.
AB  - Multiple intergenic single-nucleotide polymorphisms (SNPs) near hedgehog
      interacting protein (HHIP) on chromosome 4q31 have been strongly associated with
      pulmonary function levels and moderate-to-severe chronic obstructive pulmonary
      disease (COPD). However, whether the effects of variants in this region are
      related to HHIP or another gene has not been proven. We confirmed genetic
      association of SNPs in the 4q31 COPD genome-wide association study (GWAS) region
      in a Polish cohort containing severe COPD cases and healthy smoking controls (P =
      0.001 to 0.002). We found that HHIP expression at both mRNA and protein levels is
      reduced in COPD lung tissues. We identified a genomic region located ~85 kb
      upstream of HHIP which contains a subset of associated SNPs, interacts with the
      HHIP promoter through a chromatin loop and functions as an HHIP enhancer. The
      COPD risk haplotype of two SNPs within this enhancer region (rs6537296A and
      rs1542725C) was associated with statistically significant reductions in HHIP
      promoter activity. Moreover, rs1542725 demonstrates differential binding to the
      transcription factor Sp3; the COPD-associated allele exhibits increased Sp3
      binding, which is consistent with Sp3's usual function as a transcriptional
      repressor. Thus, increased Sp3 binding at a functional SNP within the chromosome
      4q31 COPD GWAS locus leads to reduced HHIP expression and increased
      susceptibility to COPD through distal transcriptional regulation. Together, our
      findings reveal one mechanism through which SNPs upstream of the HHIP gene
      modulate the expression of HHIP and functionally implicate reduced HHIP gene
      expression in the pathogenesis of COPD.

PMID- 22140092
TI  - Suppression of oxLDL-induced MMP-9 and EMMPRIN expression by berberine via
      inhibition of NF-kappaB activation in human THP-1 macrophages.
AB  - Upregulation of matrix metalloproteinases (MMPs) and extracellular matrix
      metalloproteinase inducer (EMMPRIN) by macrophages leads to atherosclerotic
      plaque rupture by degradation of the extracellular matrix. NF-kappaB activation
      regulates many key inflammatory genes linked to atherosclerosis. In the present
      study, the function of berberine, a natural extract from Rhizoma coptidis, on MMP
      9 and EMMPRIN expression, the role of NF-kappaB activation in oxLDL-stimulated
      macrophages, and the possible mechanism in which NF-kappaB activation is involved
      were investigated. Berberine inhibited the expression of MMP-9 and EMMPRIN at
      both mRNA and protein levels. The phosphorylation of IkappaB-alpha and nuclear
      translocation of p65 protein were reduced by berberine, suggesting that NF-kappaB
      activation was inhibited by berberine in oxLDL-stimulated macrophages. Overall,
      berberine suppressed the expression of MMP-9 and EMMPRIN by at least reducing
      partly the activity of NF-kappaB in oxLDL-induced macrophages.

PMID- 22140091
TI  - Muscle weakness in myotonic dystrophy associated with misregulated splicing and
      altered gating of Ca(V)1.1 calcium channel.
AB  - Myotonic dystrophy type 1 and type 2 (DM1 and DM2) are genetic diseases in which
      mutant transcripts containing expanded CUG or CCUG repeats cause cellular
      dysfunction by altering the processing or metabolism of specific mRNAs and
      miRNAs. The toxic effects of mutant RNA are mediated partly through effects on
      proteins that regulate alternative splicing. Here we show that alternative
      splicing of exon 29 (E29) of Ca(V)1.1, a calcium channel that controls skeletal
      muscle excitation-contraction coupling, is markedly repressed in DM1 and DM2. The
      extent of E29 skipping correlated with severity of weakness in tibialis anterior
      muscle of DM1 patients. Two splicing factors previously implicated in DM1, MBNL1
      and CUGBP1, participated in the regulation of E29 splicing. In muscle fibers of
      wild-type mice, the Ca(V)1.1 channel conductance and voltage sensitivity were
      increased by splice-shifting oligonucleotides that induce E29 skipping. In
      contrast to human DM1, expression of CUG-expanded RNA caused only a modest
      increase in E29 skipping in mice. However, forced skipping of E29 in these mice,
      to levels approaching those observed in human DM1, aggravated the muscle
      pathology as evidenced by increased central nucleation. Together, these results
      indicate that DM-associated splicing defects alter Ca(V)1.1 function, with
      potential for exacerbation of myopathy.

PMID- 22140094
TI  - Applying Bourdieu's theory to accounts of living with multimorbidity.
AB  - OBJECTIVES: Chronic illness is well researched. Broadly, empirical enquiry has
      focused on either determinants of behaviors or exploring lived experiences. This
      paper attempts to advance understandings of the lived experience of
      multimorbidity in broader cultural and structural settings. METHODS: Twenty-three
      people in their early 50s were recruited from a community health survey in
      Scotland. The participants had 4 or more chronic illnesses and were interviewed
      twice. Key concepts of Bourdieu were applied to the data set RESULTS: The
      analysis presented here is organized around 4 sections: 1) Habitus, capitals and
      the ill body; 2) Relational positioning; 3) Illness and symbolic violence; 4) The
      GP as dispenser of capitals. Applying Bourdieu's theory to the accounts
      highlighted how broader cultural structures worked their way into personal
      illness narratives and illustrated how living with multimorbidity is a dialectic
      of structure and agency. DISCUSSION: Interventions and support for those with
      multimorbidity need to take into account the tensions of opposing habitus
      underpinning medical encounters and the ongoing negotiation of structure and
      agency which is integral to living with chronic illness and underpins illness
      actions such as help-seeking and self-managing.

PMID- 22140093
TI  - Relationship of DNA damage signaling to DNA replication following treatment with
      DNA topoisomerase inhibitors camptothecin/topotecan, mitoxantrone, or etoposide.
AB  - DNA topoisomerase I (Top1) and topoisomerase II (Top2) inhibitors are widely used
      to treat a variety of cancers. Their mechanism of action involves stabilization
      of otherwise transient ("cleavable") complexes between Top1 or Top2 and DNA;
      collisions of DNA replication forks with such stabilized complexes lead to
      formation of DNA double-strand breaks (DSBs). In this study, using 5-ethynyl
      2'deoxyuridine (EdU) as a DNA precursor, we directly assessed the relationship
      between DNA replication and induction of DSBs revealed as gammaH2AX foci in A549
      cells treated with Top1 inhibitors topotecan (Tpt) or camptothecin (Cpt) and Top2
      inhibitors mitoxantrone (Mxt) and etoposide (Etp). Analysis of cells by
      multiparameter laser scanning cytometry following treatment with Tpt or Cpt
      revealed that only DNA replicating cells showed induction of gammaH2AX and a
      strong correlation between DNA replication and formation of DSBs (r = 0.86). In
      cells treated with Mxt or Etp, the correlation was weaker (r = 0.52 and 0.64). In
      addition, both Mtx and Etp caused induction of gammaH2AX in cells not replicating
      DNA. Confocal imaging of nuclei of cells treated with Tpt revealed the presence
      of gammaH2AX foci predominantly in DNA replicating cells and close association
      and co-localization of gammaH2AX foci with DNA replication sites. In cells
      treated with Mxt or Etp, the gammaH2AX foci were induced in DNA replicating as
      well as non-replicating cells but the close association between a large
      proportion of gammaH2AX foci and DNA replication sites was also apparent. The
      data are consistent with the view that collision of DNA replication forks with
      cleavable Top1-DNA complexes stabilized by Tpt/Cpt is the sole cause of induction
      of DSBs. Additional mechanisms such as involvement of transcription and/or
      generation of oxidative stress may contribute to DSBs induction by Mxt and Etp.
      The confocal analysis of the association between DNA replication sites and the
      sites of DSBs (gammaH2AX foci) opens a new approach for mechanistic studies of
      the involvement of DNA replication in induction of DNA damage.

PMID- 22140095
TI  - Sprouting of nervous fibers and upregulation of C-X-C chemokine receptor type 4
      expression in hippocampal formation of rats with enhanced spatial learning and
      memory.
AB  - Hippocampal mossy fiber sprouting following training in the Morris water maze
      (MWM) is associated with spatial learning, memory and neural plasticity. The C-X
      C chemokine receptor type 4 (CXCR4) is the main receptor for stromal cell-derived
      factor-1 (SDF-1), which is a chemokine that can regulate axonal elongation. This
      study aimed to investigate the relationship between the morphological plasticity
      of hippocampal formation and CXCR4 expression. A model of spatial learning and
      memory was established in rats by training using the MWM. Mossy fiber sprouting
      in the striatum oriens of the CA3 area of the hippocampus was found in trained
      rats by Neo-Timm's method. As shown by immunohistochemistry, the CXCR4
      immunopositive neurons were distributed in all layers and areas of hippocampal
      formation. There were no differences among groups regarding the distribution or
      shape of the immunopositive neurons. However, the immunoreactive staining
      intensity was increased in trained rats as compared with the control rats. Both
      CXCR4 gene transcription and translation were significantly upregulated in the
      trained group as compared with the control group (P < 0.01). Morphological
      plasticity in the form of axonal sprouting in the hippocampal formation can be
      induced by enhanced spatial learning and memory activity, and CXCR4 mRNA and
      protein expression is upregulated, indicating a positive correlation between
      CXCR4 expression and axonal sprouting.

PMID- 22140096
TI  - Fulvivirga imtechensis sp. nov., a member of the phylum Bacteroidetes.
AB  - A novel, Gram-staining-negative, yellow-coloured, rod-shaped, obligately aerobic,
      non-motile bacterium, designated strain AK7(T), was isolated from seawater
      collected on the coast at Visakhapatnam, Andhra Pradesh, India. The predominant
      fatty acids of the novel strain were iso-C(15 : 0), iso-C(15 : 0) 3-OH, C(16 :
      1)omega5c, iso-C(17 : 0) 3-OH and summed features 3 (C(16 : 1)omega7c and/or iso
      C(15 : 0) 2-OH) and 4 (iso-C(17 : 1) I and/or anteiso-C(17 : 1) B). The major
      respiratory quinone was MK-7 and the polar lipid profile comprised
      phosphatidylethanolamine, two unidentified aminolipids and four other
      unidentified lipids. In phylogenetic analysis based on 16S rRNA gene sequences,
      strain AK7(T) appeared most closely related to Fulvivirga kasyanovii KMM 6220(T)
      (95.9 % sequence similarity), a member of the family Flammeovirgaceae in the
      phylum Bacteroidetes. The genomic DNA G+C content of strain AK7(T) was 55.1 mol%.
      Based on the morphological, biochemical, physiological, chemotaxonomic and
      phylogenetic evidence, strain AK7(T) represents a novel species of the genus
      Fulvivirga for which the name Fulvivirga imtechensis sp. nov. is proposed. The
      type strain is AK7(T) (= MTCC 11053(T) = JCM 17390(T)).

PMID- 22140097
TI  - Neurons and a subset of interstitial cells of Cajal in the enteric nervous system
      highly express Stam2 gene.
AB  - Signal transducing adaptor molecule 2 (STAM2) is a phosphotyrosine protein, which
      is a member of the endosomal sorting complex required for transport (ESCRT-0) and
      is involved in the sorting process of the mono-ubiquitinated endosomal cargo for
      degradation in the lysosome. Analysis of gene trap mice carrying lacZ in frame
      with Stam2 revealed beta-galactosidase activity in the enteric nervous system
      (both in the myenteric and submucosal plexus) throughout the digestive tract.
      STAM2 immunostaining confirmed that the observed beta-galactosidase activity
      coincided with high Stam2 expression. To identify cell types with high Stam2
      expression, STAM2 immunostaining was colocalized with the neuronal markers
      microtubule-associated protein 2 and protein gene product 9.5 and with c-kit as a
      marker for interstitial cells of Cajal (ICCs). STAM2 and c-kit positive cells
      comprised a subset of ICCs in the enteric nervous system. Qualitative and
      quantitative analysis of the morphology of the enteric nervous system in the
      homozygous mice carrying gene trap insertion in the Stam2 gene did not reveal
      phenotype changes; therefore, STAM2 function in the digestive tube remains
      elusive.

PMID- 22140098
TI  - A systematic evaluation of the effect of thumb opponens splints on hand function
      in children with unilateral spastic cerebral palsy.
AB  - OBJECTIVE: To examine the effects of a neoprene thumb opponens splint on hand
      function during a self-selected activities of daily living task in children with
      unilateral spastic cerebral palsy with thumb-in-palm position of the affected
      hand. DESIGN: Systematic evaluation of seven cases using a multiple baseline
      design across individuals. SETTING: Outpatient clinic. SUBJECTS: Seven children
      with unilateral cerebral palsy (2-7 years old), Manual Ability Classification
      System level 2-3 participated in the study. INTERVENTIONS: Neoprene thumb
      opponens splints (McKie splint) were used. Children were followed for about four
      months. Baseline period ranged from 4 to 9 weeks, intervention period was two
      months and duration of follow-up one month. MAIN MEASURES: Hand function was
      assessed using goal attainment scaling and visual analogue scales. Data was
      assessed visually. RESULTS: In four children goal attainment scaling and/or
      visual analogue scale scores increased after introducing the splint. These
      effects remained when splints were not worn. Two children only benefited from the
      splint when it was worn. Thumb opponens splints were tolerated well by all
      children who participated in this study. CONCLUSIONS: Thumb opponens splints may
      have a positive effect on hand function in children with unilateral spastic
      cerebral palsy.

PMID- 22140100
TI  - HGPD: Human Gene and Protein Database, 2012 update.
AB  - The Human Gene and Protein Database (HGPD; http://www.HGPD.jp/) is a unique
      database that stores information on a set of human Gateway entry clones in
      addition to protein expression and protein synthesis data. The HGPD was launched
      in November 2008, and 33,275 human Gateway entry clones have been constructed
      from the open reading frames (ORFs) of full-length cDNA, thus representing the
      largest collection in the world. Recently, research objectives have focused on
      the development of new medicines and the establishment of novel diagnostic
      methods and medical treatments. And, studies using proteins and protein
      information, which are closely related to gene function, have been undertaken.
      For this update, we constructed an additional 9974 human Gateway entry clones,
      giving a total of 43,249. This set of human Gateway entry clones was named the
      Human Proteome Expression Resource, known as the 'HuPEX'. In addition, we also
      classified the clones into 10 groups according to protein function. Moreover, in
      vivo cellular localization data of proteins for 32,651 human Gateway entry clones
      were included for retrieval from the HGPD. In 'Information Overview', which
      presents the search results, the ORF region of each cDNA is now displayed
      allowing the Gateway entry clones to be searched more easily.

PMID- 22140099
TI  - Crystal structure of the DNA-bound VapBC2 antitoxin/toxin pair from Rickettsia
      felis.
AB  - Besides their commonly attributed role in the maintenance of low-copy number
      plasmids, toxin/antitoxin (TA) loci, also called 'addiction modules', have been
      found in chromosomes and associated to a number of biological functions such as:
      reduction of protein synthesis, gene regulation and retardation of cell growth
      under nutritional stress. The recent discovery of TA loci in obligatory
      intracellular species of the Rickettsia genus has prompted new research to
      establish whether they work as stress response elements or as addiction systems
      that might be toxic for the host cell. VapBC2 is a TA locus from R. felis, a
      pathogen responsible for flea-borne spotted fever in humans. The VapC2 toxin is a
      PIN-domain protein, whereas the antitoxin, VapB2, belongs to the family of
      swapped-hairpin beta-barrel DNA-binding proteins. We have used a combination of
      biophysical and structural methods to characterize this new toxin/antitoxin pair.
      Our results show how VapB2 can block the VapC2 toxin. They provide a first
      structural description of the interaction between a swapped-hairpin beta-barrel
      protein and DNA. Finally, these results suggest how the VapC2/VapB2 molar ratio
      can control the self-regulation of the TA locus transcription.

PMID- 22140101
TI  - MethylomeDB: a database of DNA methylation profiles of the brain.
AB  - MethylomeDB (http://epigenomics.columbia.edu/methylomedb/index.html) is a new
      database containing genome-wide brain DNA methylation profiles. DNA methylation
      is an important epigenetic mark in the mammalian brain. In human studies,
      aberrant DNA methylation alterations have been associated with various
      neurodevelopmental and neuropsychiatric disorders such as schizophrenia, and
      depression. In this database, we present methylation profiles of carefully
      selected non-psychiatric control, schizophrenia, and depression samples. We also
      include data on one mouse forebrain sample specimen to allow for cross-species
      comparisons. In addition to our DNA methylation data generated in-house, we have
      and will continue to include published DNA methylation data from other research
      groups with the focus on brain development and function. Users can view the
      methylation data at single-CpG resolution with the option of wiggle and
      microarray formats. They can also download methylation data for individual
      samples. MethylomeDB offers an important resource for research into brain
      function and behavior. It provides the first source of comprehensive brain
      methylome data, encompassing whole-genome DNA methylation profiles of human and
      mouse brain specimens that facilitate cross-species comparative epigenomic
      investigations, as well as investigations of schizophrenia and depression
      methylomes.

PMID- 22140102
TI  - The post-transcriptional trans-acting regulator, TbZFP3, co-ordinates
      transmission-stage enriched mRNAs in Trypanosoma brucei.
AB  - Post-transcriptional gene regulation is essential to eukaryotic development. This
      is particularly emphasized in trypanosome parasites where genes are co
      transcribed in polycistronic arrays but not necessarily co-regulated. The small
      CCCH protein, TbZFP3, has been identified as a trans-acting post-transcriptional
      regulator of Procyclin surface antigen expression in Trypanosoma brucei. To
      investigate the wider role of TbZFP3 in parasite transmission, a global analysis
      of associating transcripts was carried out. Examination of a subset of the
      selected transcripts revealed their increased abundance through mRNA
      stabilization upon TbZFP3 ectopic overexpression, dependent upon the integrity of
      the CCCH zinc finger domain. Reporter assays demonstrated that this regulation
      was mediated through 3'-UTR sequences for two target transcripts. Global
      developmental expression profiling of the cohort of TbZFP3-selected transcripts
      revealed their significant enrichment in transmissible stumpy forms of the
      parasite. This analysis of the specific mRNAs selected by the TbZFP3mRNP provides
      evidence for a developmental regulon with the potential to co-ordinate genes
      important in parasite transmission.

PMID- 22140103
TI  - Identifiers.org and MIRIAM Registry: community resources to provide persistent
      identification.
AB  - The Minimum Information Required in the Annotation of Models Registry
      (http://www.ebi.ac.uk/miriam) provides unique, perennial and location-independent
      identifiers for data used in the biomedical domain. At its core is a shared
      catalogue of data collections, for each of which an individual namespace is
      created, and extensive metadata recorded. This namespace allows the generation of
      Uniform Resource Identifiers (URIs) to uniquely identify any record in a
      collection. Moreover, various services are provided to facilitate the creation
      and resolution of the identifiers. Since its launch in 2005, the system has
      evolved in terms of the structure of the identifiers provided, the software
      infrastructure, the number of data collections recorded, as well as the scope of
      the Registry itself. We describe here the new parallel identification scheme and
      the updated supporting software infrastructure. We also introduce the new
      Identifiers.org service (http://identifiers.org) that is built upon the
      information stored in the Registry and which provides directly resolvable
      identifiers, in the form of Uniform Resource Locators (URLs). The flexibility of
      the identification scheme and resolving system allows its use in many different
      fields, where unambiguous and perennial identification of data entities are
      necessary.

PMID- 22140105
TI  - ScerTF: a comprehensive database of benchmarked position weight matrices for
      Saccharomyces species.
AB  - Saccharomyces cerevisiae is a primary model for studies of transcriptional
      control, and the specificities of most yeast transcription factors (TFs) have
      been determined by multiple methods. However, it is unclear which position weight
      matrices (PWMs) are most useful; for the roughly 200 TFs in yeast, there are over
      1200 PWMs in the literature. To address this issue, we created ScerTF, a
      comprehensive database of 1226 motifs from 11 different sources. We identified a
      single matrix for each TF that best predicts in vivo data by benchmarking
      matrices against chromatin immunoprecipitation and TF deletion experiments. We
      also used in vivo data to optimize thresholds for identifying regulatory sites
      with each matrix. To correct for biases from different methods, we developed a
      strategy to combine matrices. These aligned matrices outperform the best
      available matrix for several TFs. We used the matrices to predict co-occurring
      regulatory elements in the genome and identified many known TF combinations. In
      addition, we predict new combinations and provide evidence of combinatorial
      regulation from gene expression data. The database is available through a web
      interface at http://ural.wustl.edu/ScerTF. The site allows users to search the
      database with a regulatory site or matrix to identify the TFs most likely to bind
      the input sequence.

PMID- 22140104
TI  - Database resources of the National Center for Biotechnology Information.
AB  - In addition to maintaining the GenBank(r) nucleic acid sequence database, the
      National Center for Biotechnology Information (NCBI) provides analysis and
      retrieval resources for the data in GenBank and other biological data made
      available through the NCBI Website. NCBI resources include Entrez, the Entrez
      Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Gene, the NCBI
      Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Splign,
      RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Genome
      and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive,
      Sequence Read Archive, BioProject, BioSample, Retroviral Genotyping Tools, HIV
      1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Probe,
      Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database
      (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture
      Retrieval Tool (CDART), Biosystems, Protein Clusters and the PubChem suite of
      small molecule databases. Augmenting many of the Web applications are custom
      implementations of the BLAST program optimized to search specialized data sets.
      All of these resources can be accessed through the NCBI home page at
      www.ncbi.nlm.nih.gov.

PMID- 22140107
TI  - SNPedia: a wiki supporting personal genome annotation, interpretation and
      analysis.
AB  - SNPedia (http://www.SNPedia.com) is a wiki resource of the functional
      consequences of human genetic variation as published in peer-reviewed studies.
      Online since 2006 and freely available for personal use, SNPedia has focused on
      the medical, phenotypic and genealogical associations of single nucleotide
      polymorphisms. Entries are formatted to allow associations to be assigned to
      single genotypes as well as sets of genotypes (genosets). In this article, we
      discuss the growth of this resource and its use by affiliated software to create
      personal genome reports.

PMID- 22140106
TI  - Structural transitions in the transcription elongation complexes of bacterial RNA
      polymerase during sigma-dependent pausing.
AB  - A transcription initiation factor, the sigma(70) subunit of Escherichia coli RNA
      polymerase (RNAP) induces transcription pausing through the binding to a promoter
      like pause-inducing sequence in the DNA template during transcription elongation.
      Here, we investigated the mechanism of sigma-dependent pausing using
      reconstituted transcription elongation complexes which allowed highly efficient
      and precisely controlled pause formation. We demonstrated that, following
      engagement of the sigma subunit to the pause site, RNAP continues RNA synthesis
      leading to formation of stressed elongation complexes, in which the nascent RNA
      remains resistant to Gre-induced cleavage while the transcription bubble and RNAP
      footprint on the DNA template extend in downstream direction, likely accompanied
      by DNA scrunching. The stressed complexes can then either break sigma-mediated
      contacts and continue elongation or isomerize to a backtracked conformation.
      Suppressing of the RNAP backtracking decreases pausing and increases productive
      elongation. On the contrary, core RNAP mutations that impair RNAP interactions
      with the downstream part of the DNA template stimulate pausing, presumably by
      destabilizing the stressed complexes. We propose that interplay between DNA
      scrunching and RNAP backtracking may have an essential role in transcription
      pausing and its regulation in various systems.

PMID- 22140108
TI  - CharProtDB: a database of experimentally characterized protein annotations.
AB  - CharProtDB (http://www.jcvi.org/charprotdb/) is a curated database of
      biochemically characterized proteins. It provides a source of direct rather than
      transitive assignments of function, designed to support automated annotation
      pipelines. The initial data set in CharProtDB was collected through manual
      literature curation over the years by analysts at the J. Craig Venter Institute
      (JCVI) [formerly The Institute of Genomic Research (TIGR)] as part of their
      prokaryotic genome sequencing projects. The CharProtDB has been expanded by
      import of selected records from publicly available protein collections whose
      biocuration indicated direct rather than homology-based assignment of function.
      Annotations in CharProtDB include gene name, symbol and various controlled
      vocabulary terms, including Gene Ontology terms, Enzyme Commission number and
      TransportDB accession. Each annotation is referenced with the source; ideally a
      journal reference, or, if imported and lacking one, the original database source.

PMID- 22140110
TI  - PubChem's BioAssay Database.
AB  - PubChem (http://pubchem.ncbi.nlm.nih.gov) is a public repository for biological
      activity data of small molecules and RNAi reagents. The mission of PubChem is to
      deliver free and easy access to all deposited data, and to provide intuitive data
      analysis tools. The PubChem BioAssay database currently contains 500,000
      descriptions of assay protocols, covering 5000 protein targets, 30,000 gene
      targets and providing over 130 million bioactivity outcomes. PubChem's bioassay
      data are integrated into the NCBI Entrez information retrieval system, thus
      making PubChem data searchable and accessible by Entrez queries. Also, as a
      repository, PubChem constantly optimizes and develops its deposition system
      answering many demands of both high- and low-volume depositors. The PubChem
      information platform allows users to search, review and download bioassay
      description and data. The PubChem platform also enables researchers to collect,
      compare and analyze biological test results through web-based and programmatic
      tools. In this work, we provide an update for the PubChem BioAssay resource,
      including information content growth, data model extension and new developments
      of data submission, retrieval, analysis and download tools.

PMID- 22140109
TI  - The Arabidopsis Information Resource (TAIR): improved gene annotation and new
      tools.
AB  - The Arabidopsis Information Resource (TAIR, http://arabidopsis.org) is a genome
      database for Arabidopsis thaliana, an important reference organism for many
      fundamental aspects of biology as well as basic and applied plant biology
      research. TAIR serves as a central access point for Arabidopsis data, annotates
      gene function and expression patterns using controlled vocabulary terms, and
      maintains and updates the A. thaliana genome assembly and annotation. TAIR also
      provides researchers with an extensive set of visualization and analysis tools.
      Recent developments include several new genome releases (TAIR8, TAIR9 and TAIR10)
      in which the A. thaliana assembly was updated, pseudogenes and transposon genes
      were re-annotated, and new data from proteomics and next generation transcriptome
      sequencing were incorporated into gene models and splice variants. Other
      highlights include progress on functional annotation of the genome and the
      release of several new tools including Textpresso for Arabidopsis which provides
      the capability to carry out full text searches on a large body of research
      literature.

PMID- 22140111
TI  - The structure and selectivity of the SR protein SRSF2 RRM domain with RNA.
AB  - SRSF2 is a prototypical SR protein which plays important roles in the alternative
      splicing of pre-mRNA. It has been shown to be involved in regulatory pathways for
      maintaining genomic stability and play important roles in regulating key
      receptors in the heart. We report here the solution structure of the RNA
      recognition motifs (RRM) domain of free human SRSF2 (residues 9-101). Compared
      with other members of the SR protein family, SRSF2 structure has a longer L3 loop
      region. The conserved aromatic residue in the RNP2 motif is absent in SRSF2.
      Calorimetric titration shows that the RNA sequence 5'AGCAGAGUA3' binds SRSF2 with
      a K(d) of 61 +/- 1 nM and a 1:1 stoichiometry. NMR and mutagenesis experiments
      reveal that for SFSF2, the canonical beta1 and beta3 interactions are themselves
      not sufficient for effective RNA binding; the additional loop L3 is crucial for
      RNA complex formation. A comparison is made between the structures of SRSF2-RNA
      complex with other known RNA complexes of SR proteins. We conclude that
      interactions involving the L3 loop, N- and C-termini of the RRM domain are
      collectively important for determining selectivity between the protein and RNA.

PMID- 22140112
TI  - HIstome--a relational knowledgebase of human histone proteins and histone
      modifying enzymes.
AB  - Histones are abundant nuclear proteins that are essential for the packaging of
      eukaryotic DNA into chromosomes. Different histone variants, in combination with
      their modification 'code', control regulation of gene expression in diverse
      cellular processes. Several enzymes that catalyze the addition and removal of
      multiple histone modifications have been discovered in the past decade, enabling
      investigations of their role(s) in normal cellular processes and diverse
      pathological conditions. This sudden influx of data, however, has resulted in
      need of an updated knowledgebase that compiles, organizes and presents curated
      scientific information to the user in an easily accessible format. Here, we
      present HIstome, a browsable, manually curated, relational database that provides
      information about human histone proteins, their sites of modifications, variants
      and modifying enzymes. HIstome is a knowledgebase of 55 human histone proteins,
      106 distinct sites of their post-translational modifications (PTMs) and 152
      histone-modifying enzymes. Entries have been grouped into 5 types of histones, 8
      types of post-translational modifications and 14 types of enzymes that catalyze
      addition and removal of these modifications. The resource will be useful for
      epigeneticists, pharmacologists and clinicians. HIstome: The Histone Infobase is
      available online at http://www.iiserpune.ac.in/~coee/histome/ and
      http://www.actrec.gov.in/histome/.

PMID- 22140113
TI  - 2A peptides provide distinct solutions to driving stop-carry on translational
      recoding.
AB  - Expression of viral proteins frequently includes non-canonical decoding events
      ('recoding') during translation. '2A' oligopeptides drive one such event, termed
      'stop-carry on' recoding. Nascent 2A peptides interact with the ribosomal exit
      tunnel to dictate an unusual stop codon-independent termination of translation at
      the final Pro codon of 2A. Subsequently, translation 'reinitiates' on the same
      codon, two individual proteins being generated from one open reading frame. Many
      2A peptides have been identified, and they have a conserved C-terminal motif.
      Little similarity is present in the N-terminal portions of these peptides, which
      might suggest that these amino acids are not important in the 2A reaction.
      However, mutagenesis indicates that identity of the amino acid at nearly all
      positions of a single 2A peptide is important for activity. Each 2A may then
      represent a specific solution for positioning the conserved C-terminus within the
      peptidyl-transferase centre to promote recoding. Nascent 2A peptide:ribosome
      interactions are suggested to alter ribosomal fine structure to discriminate
      against prolyl-tRNA(Pro) and promote termination in the absence of a stop codon.
      Such structural modifications may account for our observation that replacement of
      the final Pro codon of 2A with any stop codon both stalls ribosome processivity
      and inhibits nascent chain release.

PMID- 22140114
TI  - Identification of tumor-specific Salmonella Typhimurium promoters and their
      regulatory logic.
AB  - Conventional cancer therapies are often limited in effectiveness and exhibit
      strong side effects. Therefore, alternative therapeutic strategies are demanded.
      The employment of tumor-colonizing bacteria that exert anticancer effects is such
      a novel approach that attracts increasing attention. For instance, Salmonella
      enterica serovar Typhimurium has been used in many animal tumor models as well as
      in first clinical studies. These bacteria exhibit inherent tumoricidal effects.
      In addition, they can be used to deliver therapeutic agents. However, bacterial
      expression has to be restricted to the tumor to prevent toxic substances from
      harming healthy tissue. Therefore, we screened an S. Typhimurium promoter-trap
      library to identify promoters that exclusively drive gene expression in the
      cancerous tissue. Twelve elements could be detected that show reporter gene
      expression in tumors but not in spleen and liver. In addition, a DNA motif was
      identified that appears to be necessary for tumor specificity. Now, such tumor
      specific promoters can be used to safely express therapeutic proteins by tumor
      colonizing S. Typhimurium directly in the neoplasia.

PMID- 22140115
TI  - IPAVS: Integrated Pathway Resources, Analysis and Visualization System.
AB  - Integrated Pathway Resources, Analysis and Visualization System (iPAVS) is an
      integrated biological pathway database designed to support pathway discovery in
      the fields of proteomics, transcriptomics, metabolomics and systems biology. The
      key goal of IPAVS is to provide biologists access to expert-curated pathways from
      experimental data belonging to specific biological contexts related to cell
      types, tissues, organs and diseases. IPAVS currently integrates over 500 human
      pathways (consisting of 24, 574 interactions) that include metabolic-, signaling-
      and disease-related pathways, drug-action pathways and several large process maps
      collated from other pathway resources. IPAVS web interface allows biologists to
      browse and search pathway resources and provides tools for data import,
      management, visualization and analysis to support the interpretation of
      biological data in light of cellular processes. Systems Biology Graphical
      Notations (SBGN) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
      notations are used for the visual display of pathway information. The integrated
      datasets in IPAVS are made available in several standard data formats that can be
      downloaded. IPAVS is available at: http://ipavs.cidms.org.

PMID- 22140116
TI  - Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking
      interactions.
AB  - Mammalian Musashi1 (Msi1) is an RNA-binding protein that regulates the
      translation of target mRNAs, and participates in the maintenance of cell
      'stemness' and tumorigenesis. Msi1 reportedly binds to the 3'-untranslated region
      of mRNA of Numb, which encodes Notch inhibitor, and impedes initiation of its
      translation by competing with eIF4G for PABP binding, resulting in triggering of
      Notch signaling. Here, the mechanism by which Msi1 recognizes the target RNA
      sequence using its Ribonucleoprotein (RNP)-type RNA-binding domains (RBDs), RBD1
      and RBD2 has been revealed on identification of the minimal binding RNA for each
      RBD and determination of the three-dimensional structure of the RBD1:RNA complex.
      Unique interactions were found for the recognition of the target sequence by Msi1
      RBD1: adenine is sandwiched by two phenylalanines and guanine is stacked on the
      tryptophan in the loop between beta1 and alpha1. The minimal recognition
      sequences that we have defined for Msi1 RBD1 and RBD2 have actually been found in
      many Msi1 target mRNAs reported to date. The present study provides molecular
      clues for understanding the biology involving Musashi family proteins.

PMID- 22140117
TI  - Structural insights into the Cdt1-mediated MCM2-7 chromatin loading.
AB  - Initiation of DNA replication in eukaryotes is exquisitely regulated to ensure
      that DNA replication occurs exactly once in each cell division. A conserved and
      essential step for the initiation of eukaryotic DNA replication is the loading of
      the mini-chromosome maintenance 2-7 (MCM2-7) helicase onto chromatin at
      replication origins by Cdt1. To elucidate the molecular mechanism of this event,
      we determined the structure of the human Cdt1-Mcm6 binding domains, the Cdt1(410
      440)/MCM6(708-821) complex by NMR. Our structural and site-directed mutagenesis
      studies showed that charge complementarity is a key determinant for the specific
      interaction between Cdt1 and Mcm2-7. When this interaction was interrupted by
      alanine substitutions of the conserved interacting residues, the corresponding
      yeast Cdt1 and Mcm6 mutants were defective in DNA replication and the chromatin
      loading of Mcm2, resulting in cell death. Having shown that Cdt1 and Mcm6
      interact through their C-termini, and knowing that Cdt1 is tethered to Orc6
      during the loading of MCM2-7, our results suggest that the MCM2-7 hexamer is
      loaded with its C terminal end facing the ORC complex. These results provide a
      structural basis for the Cdt1-mediated MCM2-7 chromatin loading.

PMID- 22140118
TI  - SeqTar: an effective method for identifying microRNA guided cleavage sites from
      degradome of polyadenylated transcripts in plants.
AB  - In plants, microRNAs (miRNAs) regulate their mRNA targets by precisely guiding
      cleavages between the 10th and 11th nucleotides in the complementary regions.
      High-throughput sequencing-based methods, such as PARE or degradome profiling
      coupled with a computational analysis of the sequencing data, have recently been
      developed for identifying miRNA targets on a genome-wide scale. The existing
      algorithms limit the number of mismatches between a miRNA and its targets and
      strictly do not allow a mismatch or G:U Wobble pair at the position 10 or 11.
      However, evidences from recent studies suggest that cleavable targets with more
      mismatches exist indicating that a relaxed criterion can find additional miRNA
      targets. In order to identify targets including the ones with weak
      complementarities from degradome data, we developed a computational method called
      SeqTar that allows more mismatches and critically mismatch or G:U pair at the
      position 10 or 11. Precisely, two statistics were introduced in SeqTar, one to
      measure the alignment between miRNA and its target and the other to quantify the
      abundance of reads at the center of the miRNA complementary site. By applying
      SeqTar to publicly available degradome data sets from Arabidopsis and rice, we
      identified a substantial number of novel targets for conserved and non-conserved
      miRNAs in addition to the reported ones. Furthermore, using RLM 5'-RACE assay, we
      experimentally verified 12 of the novel miRNA targets (6 each in Arabidopsis and
      rice), of which some have more than 4 mismatches and have mismatches or G:U pairs
      at the position 10 or 11 in the miRNA complementary sites. Thus, SeqTar is an
      effective method for identifying miRNA targets in plants using degradome data
      sets.

PMID- 22140119
TI  - Transcriptome-wide discovery of circular RNAs in Archaea.
AB  - Circular RNA forms had been described in all domains of life. Such RNAs were
      shown to have diverse biological functions, including roles in the life cycle of
      viral and viroid genomes, and in maturation of permuted tRNA genes. Despite their
      potentially important biological roles, discovery of circular RNAs has so far
      been mostly serendipitous. We have developed circRNA-seq, a combined
      experimental/computational approach that enriches for circular RNAs and allows
      profiling their prevalence in a whole-genome, unbiased manner. Application of
      this approach to the archaeon Sulfolobus solfataricus P2 revealed multiple
      circular transcripts, a subset of which was further validated independently. The
      identified circular RNAs included expected forms, such as excised tRNA introns
      and rRNA processing intermediates, but were also enriched with non-coding RNAs,
      including C/D box RNAs and RNase P, as well as circular RNAs of unknown function.
      Many of the identified circles were conserved in Sulfolobus acidocaldarius,
      further supporting their functional significance. Our results suggest that
      circular RNAs, and particularly circular non-coding RNAs, are more prevalent in
      archaea than previously recognized, and might have yet unidentified biological
      roles. Our study establishes a specific and sensitive approach for identification
      of circular RNAs using RNA-seq, and can readily be applied to other organisms.

PMID- 22140120
TI  - Sensitive and accurate quantification of human leukocyte migration using high
      content Discovery-1 imaging system and ATPlite assay.
AB  - Migration is a fundamental aspect of leukocyte behavior and represents a
      significant therapeutic target clinically. However, most migration assays used in
      research are relatively low throughput and not easily compatible with rapid
      analysis or high-throughput screening (HTS) protocols required for drug screening
      assays. We therefore investigated the quantification of the migration of human
      leukocytes using the Molecular Devices high-content Discovery-1 platform or
      PerkinElmer ATPlite assay compared to manual counting. We have conducted
      extensive assay validation, investigating the detection limits, sensitivity, and
      precision of each method to count human leukocytes. Leukocyte migration assays
      were conducted using 96-well HTS-Transwell plates and the potent chemokine
      stromal cell-derived factor-1 (SDF-1). We reveal that the Discovery-1 and ATPlite
      methods developed here provide useful approaches to quantify leukocyte migration
      in an HTS manner with high levels of detection, sensitivity, and precision.

PMID- 22140121
TI  - A high-throughput screening method for small-molecule inhibitors of the aberrant
      mutant SOD1 and dynein complex interaction.
AB  - Aberrant protein-protein interactions are attractive drug targets in a variety of
      neurodegenerative diseases due to the common pathology of accumulation of protein
      aggregates. In amyotrophic lateral sclerosis, mutations in SOD1 cause the
      formation of aggregates and inclusions that may sequester other proteins and
      disrupt cellular processes. It has been demonstrated that mutant SOD1, but not
      wild-type SOD1, interacts with the axonal transport motor dynein and that this
      interaction contributes to motor neuron cell death, suggesting that disrupting
      this interaction may be a potential therapeutic target. However, it can be
      challenging to configure a high-throughput screening (HTS)-compatible assay to
      detect inhibitors of a protein-protein interaction. Here we describe the
      development and challenges of an HTS for small-molecule inhibitors of the mutant
      SOD1-dynein interaction. We demonstrate that the interaction can be formed by
      coexpressing the A4V mutant SOD1 and dynein intermediate complex in cells and
      that this interaction can be disrupted by compounds added to the cell lysates.
      Finally, we show that some of the compounds identified from a pilot screen to
      inhibit the protein-protein interaction with this method specifically disrupt the
      interaction between the dynein complex and mtSOD1 but not the dynein complex
      itself when applied to live cells.

PMID- 22140122
TI  - Mild decrease in estimated glomerular filtration rate and proteinuria are
      associated with all-cause and cardiovascular mortality in the general population.
AB  - BACKGROUND: A recent collaborative meta-analysis by Kidney Disease: Improving
      Global Outcomes reported that an estimated glomerular filtration rate (eGFR) <60
      mL/min/1.73 m(2) and an albumin-to-creatinine ratio of >= 10 mg/g were
      independent predictors for mortality in the general population. However,
      selection bias, heterogeneity of the cohorts and measurement issues could be
      limitations. METHODS: We analyzed the relationship of eGFR and proteinuria with
      mortality in the Korean general population, represented by 112,115 participants,
      aged >= 20 years, who had a voluntary health check-up with homogenous calibration
      of creatinine measurement from 2003 to 2009. Proteinuria (trace or more) was
      determined by urine dipstick. RESULTS: eGFR and proteinuria were independently
      associated with all-cause mortality (ACM) and cardiovascular mortality (CVM), and
      progressive increases in risks for mortality were noted according to eGFR level
      and the presence of proteinuria. Compared with eGFR 90-105 mL/min/1.73 m(2),
      hazard ratio (HRs) for ACM were 1.60 [95% confidence interval (CI) 1.12-2.30] for
      eGFR 60-74 mL/min/1.73 m(2) and 3.54 (2.20-5.68) for eGFR <60 mL/min/1.73 m(2) in
      participants with no proteinuria. In participants with proteinuria, HRs for ACM
      were 2.10 (1.41-3.12) for eGFR 75-89 mL/min/1.73 m(2), 2.30 (1.50-3.53) for eGFR
      60-74 mL/min/1.73 m(2) and 3.77 (2.15-6.38) for eGFR <60 mL/min/1.73 m(2).
      Similar findings were observed for CVM. CONCLUSIONS: eGFR <75 mL/min/1.73 m(2)
      and urine dipstick trace or more were independent risk factors of ACM and CVM.
      The risks of adverse outcomes are greater in the general population with mild
      renal impairment or mild proteinuria.

PMID- 22140123
TI  - Changes in fibroblast growth factor 23 during treatment of secondary
      hyperparathyroidism with alfacalcidol or paricalcitol.
AB  - BACKGROUND: Fibroblast growth factor 23 (FGF23) increases renal phosphate
      excretion and decreases the formation of 1,25 dihydroxyvitamin D. In patients
      with chronic kidney disease, plasma FGF23 levels are markedly elevated by unknown
      mechanisms. We explored the changes in FGF23 during treatment of secondary
      hyperparathyroidism (SHPT) with alfacalcidol or paricalcitol in haemodialysis
      patients. METHODS: Intravenous alfacalcidol and paricalcitol were compared in
      haemodialysis patients with SHPT in a randomized 2 * 16-week cross-over study,
      with 6 weeks washout period preceding treatment and between treatment periods. In
      57 of the enrolled patients, blood samples were frozen before and after each
      treatment period and available for measurement of FGF23. RESULTS: Treatment with
      both analogues increased FGF23 (P < 0.05 in all treatment periods). The magnitude
      of increase was similar for alfacalcidol and paricalcitol (Period 1: 223 versus
      314%; P = 0.384 and Period 2: 174 versus 227%; P = 0.510) and the levels returned
      to pre-treatment levels during the washout period. Independent predictors of rise
      in FGF23 were baseline levels of FGF23 (P < 0.01), changes in ionized calcium (P
      < 0.01) and phosphate (P < 0.01) and cumulative dose of vitamin D analogues (P =
      0.024). CONCLUSION: Alfacalcidol and paricalcitol increase the plasma levels of
      FGF23 equally and substantially in haemodialysis patients.

PMID- 22140124
TI  - Effects of cinacalcet treatment on serum soluble Klotho levels in haemodialysis
      patients with secondary hyperparathyroidism.
AB  - BACKGROUND: Klotho is a transmembrane protein that acts as a cofactor for
      fibroblast growth factor 23 (FGF23). Klotho also exists as a soluble circulating
      protein, but its role in secondary hyperparathyroidism (SHPT) is largely unknown.
      METHODS: We measured serum soluble Klotho levels in 51 haemodialysis patients,
      who participated and completed a 52-week, multicentre, open-label single-arm
      trial that examined the effectiveness of cinacalcet for treating SHPT. RESULTS:
      After 12 weeks of cinacalcet treatment, serum soluble Klotho decreased
      significantly (P = 0.03) but only marginally from 398 pg/mL [interquartile range
      (IQR), 268-588 pg/mL] to 378 pg/mL (IQR, 266-568 pg/mL) and returned to baseline
      levels. There were no significant associations between the changes in soluble
      Klotho levels and changes in any other parameters of mineral metabolism,
      including serum calcium, phosphorus, intact parathyroid hormone and FGF23.
      CONCLUSION: Despite significant alterations in mineral and bone metabolism during
      treatment with cinacalcet, this resulted in only small and transient reductions
      in serum levels of soluble Klotho.

PMID- 22140125
TI  - Neuropsychological profile of children with kidney transplants.
AB  - BACKGROUND: Varying results on the cognitive outcome of children who have
      undergone kidney transplantation (KTx) have raised concern for specific
      neurocognitive difficulties. METHODS: Fifty children with KTx were assessed at a
      mean age of 11.1 (SD 3.2; range 6.3-16.4), on average 6.9 (SD 3.6; range 1.0
      14.1) years post-operatively. A standardized test of intelligence [Wechsler
      Intelligence Scale for Children (WISC-III)] and neuropsychological tests from
      NEPSY-II were administered. The neuropsychological profile of KTx children was
      compared to that of a control group matched for gender, age and maternal
      education. RESULTS: The KTx children had a lower intelligence quotient (83.9)
      than the test norms (100.0, P < 0.001). On neuropsychological assessment, the KTx
      group scored generally lower than the control group did (P < 0.001). The
      difference was evident in both the verbal and visuospatial domains, on a sub-test
      of complex auditory attention, verbal working memory and facial affect
      recognition. When children with neurological co-morbidity were excluded, the
      remaining group still scored lower than the controls did on Comprehension of
      Instructions (P = 0.06), Design Copying (P = 0.007) and Affect Recognition (P =
      0.018). A better cognitive outcome was mainly associated with the absence of
      neurological co-morbidity, younger age, shorter disease duration and sustained
      kidney function. Children with congenital nephrosis had a similar outcome to
      those with other diagnoses. CONCLUSIONS: KTx children exhibit a pattern of
      effects in their cognitive outcome in which both the visuospatial and language
      domains are affected, but visual memory and simple auditory attention remain
      intact. Patients without neurological co-morbidity exhibit impairment in
      receptive language, visuospatial functions and in recognizing emotional states.

PMID- 22140127
TI  - Psychogenic movement disorders in children: characteristics and predictors of
      outcome.
AB  - Psychogenic movement disorders are defined as hyperkinetic or hypokinetic
      movement disorders associated with underlying psychological disorders.
      Psychogenic movement disorders account for 1% to 9% of all neurologic diagnoses.
      The assessment and treatment of psychogenic movement disorders can be complex. We
      report patients seen over the past 5 years, diagnosed with psychogenic movement
      disorder. We discuss in this article some patient characteristics and some
      strategies that are effective in the management of this group of patients. The
      case examples presented in the current article demonstrate the importance of two
      factors, a multidisciplinary approach and engaging the family, that are essential
      components in the treatment of psychogenic movement disorders.

PMID- 22140126
TI  - Indoxyl sulphate inhibits osteoclast differentiation and function.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) develop various bone
      abnormalities characterized by impaired bone remodelling. Recent data suggest
      that accumulation of the uraemic toxin indoxyl sulphate (IS) may be one of the
      factors involved in bone abnormalities in CKD patients. Indeed, it was recently
      reported that IS induces skeletal resistance to parathyroid hormone in cultured
      osteoblastic cells. However, it is not yet known whether IS also affects
      osteoclast cells. METHODS: In the present study, we assessed the direct effect of
      IS at uraemic concentrations and in the presence (to reach the 3 mM
      concentration) or absence of added inorganic phosphate (Pi) on osteoclast (OCL)
      differentiation and bone-resorbing activity in two well-established cellular
      models of monocyte/macrophage (peripheral blood mononuclear cells and the RAW
      264.7 cell line). RESULTS: We found that IS inhibits both OCL differentiation and
      bone-resorbing activity in a dose-dependent manner and that these effects were
      enhanced in the presence of Pi at 3mM concentration. IS induced a gradual
      inhibition of JNK, Akt, p38, ERK1/2 phosphorylation and AP-1 DNA-binding
      activity. The effects of IS on OCL differentiation and AP-1 were prevented by
      probenecid, a competitive inhibitor of organic anion transporters, suggesting
      that IS's effects occur subsequently to its intake. CONCLUSION: Our findings
      strongly suggest that IS not only inhibits osteoblast function but also has an
      inhibitory effect on OCL function and thus could affect bone remodelling in CKD
      patients.

PMID- 22140128
TI  - Neurologic presentation, diagnostics, and therapeutic insights in a severe case
      of adenylosuccinate lyase deficiency.
AB  - Epilepsy in adenylosuccinate lyase deficiency may be difficult to treat, and
      there is no standardized therapy. The authors describe a case of severe
      adenylosuccinate lyase deficiency resulting from a heterozygous mutation of the
      ADSL gene (p.D215H/p.I351T). The patient presented with tonic-clonic seizures,
      opisthotonus, tremor, and myoclonus in the 4th day of life. The seizures were
      refractory on various combinations of antiepileptic treatment. A ketogenic diet
      was introduced at the age of 2 resulting in a seizure-free period. The patient,
      however, developed a metabolic hyperchloremic acidosis with Fanconi syndrome,
      which disappeared a month after cessation of the diet at the age of 5. Since the
      withdrawal of the ketogenic diet, seizures have returned to a frequency of
      several times a day. In conclusion, a ketogenic diet could be considered a valid
      therapeutic option in patients with intractable seizures in a course of
      adenylosuccinate lyase deficiency; however, it requires a formal study.

PMID- 22140129
TI  - Thoracic myelopathy secondary to seizure following scoliosis surgery.
AB  - The incidence of spinal injuries is increased in people with epilepsy although
      compressive thoracic myelopathy has not been reported. We describe a 15-year-old
      girl with SCN1A mutation (Dravet syndrome), refractory generalized tonic-clonic
      seizures, and prior posterior instrumentation and fusion for scoliosis, who
      presented with progressive lower extremity weakness. Junctional kyphosis with
      disc herniation and spinal cord compression directly rostral to the
      instrumentation was apparent on imaging. On history, the patient had suffered a
      particularly severe convulsive seizure just before developing symptoms. Surgical
      decompression and stabilization led to a complete neurologic recovery. This
      unusual presentation of myelopathy illustrates the need to consider this
      complication in patients with epilepsy and spinal instrumentation.

PMID- 22140130
TI  - Hereditary sensory and autonomic neuropathy with autonomic crises: a Turkish
      variant of familial dysautonomia?
AB  - Hereditary sensory and autonomic neuropathies have different phenotypes. We
      report 2 cousins with differing clinical courses of a hereditary sensory and
      autonomic neuropathy. The progressive disease in case 1 is dominated by loss of
      sensation, autonomic crises, and pain. Case 2 shows loss of sensation, mental
      retardation, and deafness, clinically similar to patients with hereditary sensory
      and autonomic neuropathy type II. Detailed molecular studies in case 1 for all
      known genes that are associated with hereditary sensory and autonomic
      neuropathies were negative. However, the occurrence of the 2 cases within 1
      kindred makes a common genetic background likely. We, therefore, propose a
      Turkish variant of familial dysautonomia in these 2 patients.

PMID- 22140131
TI  - Can diffusion tensor imaging (DTI) identify epileptogenic tubers in tuberous
      sclerosis complex? Correlation with alpha-[11C]methyl-L-tryptophan ([11C] AMT)
      positron emission tomography (PET).
AB  - In this study, we determined whether diffusion tensor imaging (DTI), a more
      widely available imaging modality, is as effective as alpha-[(11)C]methyl-l
      tryptophan (AMT)-positron emission tomography (PET) in localizing epileptogenic
      tubers in tuberous sclerosis complex. Following that, coregistration of AMT-PET
      and diffusion tensor imaging scans apparent diffusion coefficient (ADC) and
      fractional anisotropy (FA) were measured in all tubers using a region-of-interest
      approach and were compared with AMT-PET tuber/cortex uptake ratios, which were
      used to differentiate between epileptogenic and nonepileptogenic tubers. Forty
      three tubers, out of a total of 320 tubers, had AMT-PET uptake ratios greater
      than 1 and hence were classified as potentially epileptogenic. FA in
      epileptogenic tubers was reduced compared with the other tubers (P = .03). A
      significant negative correlation was observed between AMT-PET uptake ratio of
      epileptogenic tubers and FA values (r = -.45; P = .003). Tubers with higher AMT
      PET uptake ratios corresponded well with lower FA values in tuberous sclerosis
      complex patients.

PMID- 22140132
TI  - Three-dimensional microstructural changes in murine abdominal aortic aneurysms
      quantified using immunofluorescent array tomography.
AB  - This study investigated the spatial and temporal remodeling of blood vessel wall
      microarchitecture and cellular morphology during abdominal aortic aneurysm (AAA)
      development using immunofluorescent array tomography (IAT), a high-resolution
      three-dimensional (3D) microscopy technology, in the murine model. Infrarenal
      aortas of C57BL6 mice (N=20) were evaluated at 0, 7, and 28 days after elastase
      or heat-inactivated elastase perfusion. Custom algorithms quantified volume
      fractions (VF) of elastin, smooth muscle cell (SMC) actin, and adventitial
      collagen type I, as well as elastin thickness, elastin fragmentation, non
      adventitial wall thickness, and nuclei amount. The 3D renderings depicted elastin
      and collagen type I degradation and SMC morphological changes. Elastin VF
      decreased 37.5% (p<0.01), thickness decreased 48.9%, and fragmentation increased
      449.7% (p<0.001) over 28 days. SMC actin VF decreased 78.3% (p<0.001) from days 0
      to 7 and increased 139.7% (p<0.05) from days 7 to 28. Non-adventitial wall
      thickness increased 61.1%, medial nuclei amount increased 159.1% (p<0.01), and
      adventitial collagen type I VF decreased 64.1% (p<0.001) over 28 days. IAT and
      custom image analysis algorithms have enabled robust quantification of vessel
      wall content, microstructure, and organization to help elucidate the dynamics of
      vascular remodeling during AAA development.

PMID- 22140133
TI  - YKL-40 is differentially expressed in human embryonic stem cells and in cell
      progeny of the three germ layers.
AB  - The secreted glycoprotein YKL-40 participates in cell differentiation,
      inflammation, and cancer progression. High YKL-40 expression is reported during
      early human development, but its functions are unknown. Six human embryonic stem
      cell (hESC) lines were cultured in an atmosphere of low or high oxygen tension,
      in culture medium with or without basic fibroblast growth factor, and on feeder
      layers comprising mouse embryonic fibroblasts or human foreskin fibroblasts to
      evaluate whether hESCs and their progeny produced YKL-40 and to characterize YKL
      40 expression during differentiation. Secreted YKL-40 protein and YKL-40 mRNA
      expression were measured by enzyme-linked immunosorbent assay (ELISA) and
      quantitative RT-PCR. Serial-sectioned colonies were stained for YKL-40 protein
      and for pluripotent hESC (OCT4, NANOG) and germ layer (HNF-3beta, PDX1, CD34,
      p63, nestin, PAX6) markers. Double-labeling showed YKL-40 expression in OCT4
      positive hESCs, PAX6-positive neuroectodermal cells, and HNF-3beta-positive
      endodermal cells. The differentiating progeny showed strong YKL-40 expression.
      Abrupt transition between YKL-40 and OCT4-positive hESCs and YKL-40-positive ecto
      and neuroectodermal lineages was observed within the same epithelial-like layer.
      YKL-40-positive cells within deeper layers lacked contact with OCT4-positive
      cells. YKL-40 may be important in initial cell differentiation from hESCs toward
      ectoderm and neuroectoderm, with retained epithelial morphology, whereas later
      differentiation into endoderm and mesoderm involves a transition into the deeper
      layers of the colony.

PMID- 22140134
TI  - Angiotensin receptor blockade attenuates glomerulosclerosis progression by
      promoting VEGF expression and bone marrow-derived cells recruitment.
AB  - BACKGROUND: Previous studies have demonstrated that angiotensin Type I receptor
      blockade (ARB) reduces proteinuria, reverses glomerular injury and
      glomerulosclerosis in rat models of diabetic nephropathy and glomerulonephritis.
      However, the cellular and molecular mechanisms are unclear. To investigate the
      role of cells of the bone marrow (BM) in glomerular repair seen during ARB
      administration, we induced progressive glomerulosclerosis in enhanced green
      fluorescent protein BM chimeric rats by a single injection of anti-Thy 1.1
      monoclonal antibody, followed by unilateral nephrectomy. METHODS: Cohorts of rats
      received valsartan or no treatment from Week 2 to Week 8 after induction of
      disease. Renal function, urinary protein excretion and histological changes were
      examined 8 weeks after anti-Thy-1.1 monoclonal antibody injection. RESULTS:
      Valsartan administration improved renal function, reduced severity of
      glomerulosclrosis and markedly reduced mortality. Valsartan administration
      promoted regeneration of the glomerular tuft, lowered proteinuria and resulted in
      enhanced vascular endothelial growth factor (VEGF) expression in the cortex and
      glomerular tuft. In addition, valsartan promoted increased recruitment of BM
      derived cells (BMDCs) many of which expressed VEGF and likely contributed
      directly to glomerular repair. Nearly all BMDCs recruited to the glomerulus
      expressed the monocyte/macrophage marker CD68. CONCLUSIONS: In conclusion, the
      data shows that ARB by valsartan prevents glomerulosclerosis progression by
      enhancing glomerular capillary repair which is associated with the recruitment of
      VEGF producing 'reparative' monocytes and macrophages from the BM.

PMID- 22140135
TI  - Glomerular hyperfiltration in prediabetes and prehypertension.
AB  - BACKGROUND: This study aimed to investigate the associations of hyperfiltration
      and hypofiltration with prediabetes and prehypertension. METHODS: The study
      subjects included 99 140 people aged 20-89 years who underwent health checkups in
      Aichi Prefecture, Japan. The prevalence of hyperfiltration [estimated glomerular
      filtration rate (eGFR) above the age-/sex-specific 95th percentile] and
      hypofiltration (eGFR below the age-/sex-specific 5th percentile) was compared
      among stages of prediabetes (fasting plasma glucose <100, 100-109, 110-125 and
      >=126 mg/dL for no prediabetes, Stage 1 prediabetes, Stage 2 prediabetes and
      diabetes, respectively) and prehypertension [blood pressure (BP) <120/80, 120
      129/80-84, 130-139/85-89 and >=140/90 mmHg for no prehypertension, Stage 1
      prehypertension, Stage 2 prehypertension and hypertension, respectively).
      RESULTS: The prevalence of hyperfiltration increased with increasing stage of
      prediabetes [odds ratios (ORs): 1.29, 1.58 and 2.47 for Stage 1 prediabetes,
      Stage 2 prediabetes and diabetes, respectively] and prehypertension (ORs: 1.10,
      1.33 and 1.52 for Stage 1 prehypertension, Stage 2 prehypertension and
      hypertension, respectively). Hypofiltration was not associated with prediabetes
      or prehypertension. CONCLUSIONS: The prevalence of glomerular hyperfiltration
      increased with increasing stages of prediabetes and prehypertension. Therefore,
      kidney function should be monitored in subjects with prediabetes or
      prehypertension. In subjects with hyperfiltration, earlier treatment of
      hyperglycemia and high BP may be necessary to prevent the development of kidney
      damage.

PMID- 22140137
TI  - Estimating the proportion of intracranial aneurysms likely to be amenable to
      treatment with the pipeline embolization device.
AB  - OBJECTIVE: A study was undertaken to estimate the fraction of intracranial
      aneurysms that might be amenable to treatment with the pipeline embolization
      device (PED), a current flow diverter device, and to determine the types of
      aneurysms that are probably not amenable to treatment with this device. METHODS:
      A retrospective analysis of 200 consecutive intracranial aneurysms as seen on
      three-dimensional rotational angiography images was conducted. Based on aneurysm
      and parent artery morphology, four independent observers experienced in the use
      of the PED judged the likelihood that a given aneurysm could theoretically be
      treated with one or more PED using a 5-point scale: grades 1 and 2 indicated
      amenability to treatment with multiple devices; grade 3 indicated amenability to
      treatment with one device; and grades 4 and 5 indicated the aneurysm would not be
      amenable to treatment with the PED. Aneurysms were analyzed on the basis of
      anatomical factors only. Rupture status was not considered. Interobserver
      agreement was determined. RESULTS: 94 of 200 aneurysms (47%) were judged to be
      likely to be amenable to treatment with the PED; 50 cases (25%) were judged to be
      amenable to the use of multiple overlapping devices while, in 44 cases (22%),
      coverage with a single device was preferred. There was a significant relationship
      between the location of the aneurysm and the grade of the aneurysm (p<0.0001).
      CONCLUSION: On the basis of anatomical configuration, nearly half of the
      aneurysms in this study were likely to be amenable to treatment with the PED.

PMID- 22140136
TI  - An observational cohort study of extended dosing (once every 2 weeks or once
      monthly) regimens with darbepoetin alfa in patients with chronic kidney disease
      not on dialysis: the EXTEND study.
AB  - BACKGROUND: Darbepoetin alfa (DA) has been shown to be an effective treatment of
      anaemia in patients with chronic kidney disease (CKD) not on dialysis (NoD).
      EXTEND is an observational study assessing the effectiveness of DA administered
      once biweekly (Q2W) or monthly (QM) in a general CKD-NoD population. METHODS:
      Adult CKD-NoD patients starting DA Q2W/QM treatment in June 2006 or later were
      eligible. Retrospective and/or prospective data including haemoglobin levels and
      erythropoiesis-stimulating agent (ESA) dosing were collected for 6 months before
      and 12 months after DA initiation. Mean Hb levels were calculated every 3 months,
      and ESA dose was converted to a geometric mean weekly DA equivalent dose and
      summarized monthly. RESULTS: Data from 4278 patients showed that patients
      receiving ESA treatment before DA Q2W/QM initiation had a mean (95% confidence
      interval) Hb level of 11.9 g/dL (11.8-12.0 g/dL) at initiation and 11.6 g/dL
      (11.6-11.7 g/dL) at Months 10-12, with mean ESA dose of 22 MUg/week (21-23
      MUg/week) prior to initiation, 16 MUg/week (15-16 MUg/week) at initiation and 16
      MUg/week (15-16 MUg/week) at Month 12. In ESA-naive patients, Hb levels increased
      from 10.3 g/dL (10.2-10.3 g/dL) at initiation to 11.7 g/dL at Months 4-6 and were
      maintained at a mean level of 11.7 g/dL (11.7-11.8 g/dL) at Months 10-12, with
      mean ESA dose of 16 MUg/week (16-17 MUg/week) at initiation and 16 MUg/week (16
      17 MUg/week) at Month 12. In the 85% of patients receiving DA at extended
      intervals (Q2W or less frequently) at Month 12, 12 patients (0.3%) experienced DA
      related adverse reactions. CONCLUSION: DA Q2W/QM was an effective treatment of
      anaemia in the general CKD-NoD patient population and a dose increase was not
      required in patients switching from a previous ESA regimen.

PMID- 22140138
TI  - A review of measles.
AB  - Measles, once a common childhood illness that many older school nurses could
      recognize without difficulty, needs review again after reemerging from Europe and
      other continents. A highly contagious disease, which has been referenced since
      the seventh century, the virus can cause serious illness and death, despite the
      fact that it is vaccine preventable. School nurses are wise to review the
      pathogenesis, occurrences, incubation, and communicability as well as methods to
      diagnose and treat measles in order to prevent an outbreak.

PMID- 22140139
TI  - Managing encopresis in the elementary school setting: the school nurse's role.
AB  - Encopresis is a medical condition that is associated with incontinence in
      children. It leads to frustration and anxiety in both parents and children due to
      the presenting symptoms and the inability to control elimination patterns. There
      is overwhelming concern among families that a child with encopresis will be
      ostracized from peers and will suffer long-term psychological effects. It is
      therefore important to define encopresis to include the etiology, prevalence, and
      treatment measures in order to ensure a positive outcome. In addition, as a child
      enters elementary school, the school nurse plays a vital role in assisting the
      child to reach educational goals and managing health concerns. This article will
      guide the reader through the origin and diagnosis of encopresis as well as the
      principles of management. It will also delineate the school nurse role in
      managing encopresis in the school setting.

PMID- 22140140
TI  - Teacher time spent on student health issues and school nurse presence.
AB  - Elementary school teacher time spent on student health issues and the
      relationship to school nurse services was the focus of this 2-year study. A cross
      sectional design was used to survey traditional and exceptional (special needs)
      classroom teachers about the time they spent on health issues and their
      perception of school nurse presence. The school nurses were surveyed regarding
      the impact of their presence on early releases due to illness. Study findings
      related to teacher perceptions indicate with school nurse presence there are
      fewer early releases, increased communication, less time spent on health issues,
      students with chronic illnesses are safer, and there is a resource available for
      health information. The data provide the groundwork for discussions to improve
      the communication of the nurses' schedules, increase teacher confidence in
      consistent nurse hours at their school and aid the nurse in protecting valuable
      on-site school hours from other interferences or commitments.

PMID- 22140141
TI  - Psychological vulnerability among overweight/obese minority adolescents.
AB  - Depression is associated with obesity among adolescents, with racial/ethnic
      variability noted. Psychological correlates that may influence this relationship
      have not been adequately explored. The primary objective of this secondary
      analysis was to compare levels of stress, self-esteem, coping, social support,
      and depressive mood between normal weight and overweight/obese minority
      adolescents (as defined using Centers for Disease Control and Prevention
      standards). Adolescents (n = 101) aged 14-18 years who were largely minority
      (87%) were recruited from two Midwestern-area high schools. Using a descriptive
      comparative design, individuals were grouped into normal weight (>5th to <85th
      percentile) and overweight/obese (>= 85 th percentile) for comparison on
      measures. Self-reported levels of stress, coping, self-esteem, social support,
      depressive mood, and body mass index were obtained. Obese/overweight adolescents
      reported significantly lower self-esteem than did those with normal weight (p <
      .05). Although stress was a significant predictor of depressive mood in both
      groups (p < .001), low self-esteem was also a significant predictor of depressive
      mood in the overweight/obese group (p = .001). Strategies to manage stress and
      improve self-esteem may help alleviate depressive mood in high school
      adolescents.

PMID- 22140142
TI  - Comparison of QuantiFERON-TB Gold test and tuberculin skin test for the
      identification of latent Mycobacterium tuberculosis infection in lupus patients.
AB  - The tuberculin skin test (TST) has low sensitivity for the diagnosis of
      tuberculosis (TB). QuantiFERON-TB Gold (QFT-G) is an IFN-gamma-release assay that
      measures the release of interferon-gamma after stimulation in vitro by
      Mycobacterium tuberculosis antigens using ELISA. The main advantage of this assay
      compared with TST is the lack of cross-reaction with Bacillus Calmette-Guerin
      (BCG) as well as most of non-tuberculous mycobacteria. The aim of our study is to
      compare QFT-G with TST for the detection of latent tuberculosis infection (LTBI)
      among patients with systemic lupus erythematosus (SLE). METHODS: Seventy-eight
      patients with SLE and 49 healthy subjects (HCs) participated in the study. All
      patients and controls were interviewed for a history of TB then BCG vaccinations
      were recorded and chest X-rays were examined for a sign of TB infection. QTF-G
      and TST were performed on both patients and controls. QTF-G results were recorded
      as positive, negative or indeterminate. A positive TST for SLE was defined as >=5
      mm. RESULTS: Seventy-six SLE patients (97.4%) had been BCG vaccinated. Similar to
      the HC (28.5%), 19 of 78 (24.3%) SLE patients had positive QTF-G. Two patients
      had an indeterminate result. The agreement between QTF-G and TST was 49/76
      (64.4%) (kappa = 0.33). There were fewer positive QFT-G test results than
      positive TST results (24.3% vs. 50%; p < 0.01). Twenty-two (28.9%) patients were
      TST(+)/QTF-G(-) while only 3(3.9%) patients were TST(-)/QTF-G(+). When the
      positive TST was defined as >=10 mm indurations, which is the cut-off in
      screening for LTBI in Turkey, the agreement between two tests increased up to
      58/76 (76.3%) with a kappa value of 0.47. The mean TST measurements was higher in
      QTF-G positive patients (13.4 +/- 8.8 mm) than the QTF-G negative patients (4 +/-
      5.3 mm) (p < 0.001). DISCUSSION: In a TB-endemic and BCG vaccinated population,
      the QuantiFERON-TB Gold assay seemed to be a more accurate test for the detection
      of LTBI in SLE patients. Although 5 mm is usually accepted to be the standard cut
      off for TST in immunocompromised patients such as SLE, the level of agreement
      between QTF-G and TST was better with a 10 mm cut-off in our population.

PMID- 22140143
TI  - Discordant spectrum of cardiac manifestations of neonatal lupus in twins.
AB  - Congenital complete heart block associated with transplacental passage of
      maternal autoantibodies reactive with SSA/Ro and SSB/La is a rare disease with
      significant fetal, neonatal, and childhood morbidity and mortality. We present
      the case of dichorionic, diamniotic twins (female twin A and male twin B) exposed
      to maternal Ro and La autoantibodies with different disease expression. Twin A
      (female) had Mobitz type I second degree atrioventricular (AV) block
      (Wenckebach); twin B (male) had normal sinus rhythm. Both twins had structurally
      normal hearts but demonstrated echocardiographic evidence of endocardial
      fibroelastosis (EFE). Following maternal dexamethasone 4 mg once daily, twin A
      reverted to sinus rhythm in utero; twin B remained in sinus rhythm throughout
      pregnancy. Echocardiograms after delivery demonstrated resolution of EFE in both
      fetuses, and EKGs confirmed sinus rhythm. However, at five months of age, Holter
      monitor demonstrated first degree AV block and intermittent Wenckebach in twin A.
      Twin B remains in sinus rhythm. This case is one of only three in the literature
      that describes Mobitz type I second degree atrioventricular block presenting in
      fetuses exposed to maternal SSA and SSB autoantibodies and is the first case that
      we have seen reported in twins. Importantly, this case also adds to the growing
      body of literature describing EFE as a presentation of neonatal lupus with or
      without conduction system abnormalities, emphasizes the spectrum of cardiac
      conduction abnormalities in neonatal lupus syndrome, and raises interesting
      questions about discordant disease expression in twins.

PMID- 22140144
TI  - Underestimation of menthol cigarette use among young US Black smokers: comment on
      the article by rock et Al.

PMID- 22140146
TI  - Evaluation of the effect of ammonia on nicotine pharmacokinetics using rapid
      arterial sampling.
AB  - INTRODUCTION: The nicotine bolus theory states that the dependence-producing
      potential of cigarettes relates to a rapid increase in nicotine at brain receptor
      sites. It has been suggested that ammonia, a compound typically found in tobacco
      products, further increases the amount of nicotine absorbed and its absorption
      rate. The aim of this study was to determine whether different ammonia yields in
      cigarettes affected the rate or amount of nicotine absorption from the lungs to
      arterial circulation. METHODS: 34 adult smokers received 3 separate puffs from
      each of 2 test cigarettes with different ammonia yields (ammonia in smoke: 10.1
      MUg per cigarette vs. 18.9 MUg per cigarette), followed by rapid radial arterial
      blood sampling (maximum one sample per second) with 30 min between puffs.
      Arterial blood samples were assayed for nicotine by liquid chromatography tandem
      mass spectrometry. Pharmacokinetic modeling was performed and the two test
      cigarettes were assessed for bioequivalence. RESULTS: No significant differences
      were found in area under the curve, C(max), or T((max)) and the 2 test cigarettes
      were found to be bioequivalent based on 2 one-sided tests at a significance level
      of 5%. In addition, the zero-order rate constant (k(0)) obtained from the initial
      slope of the curves and the model-dependent first-order rate constant (k(a)) were
      not significantly different. CONCLUSIONS: This study provides strong evidence
      that the different ammonia yields of the test cigarettes had no impact on
      nicotine pharmacokinetics; thus, the ammonia did not increase the rate or amount
      of nicotine absorption from a puff of cigarette smoke.

PMID- 22140145
TI  - Subjective reactivity to smoking cues as a predictor of quitting success.
AB  - INTRODUCTION: Acutely increased urge to smoke, or craving, in response to smoking
      cues (i.e., "cue reactivity") is often believed to identify those less able to
      later quit smoking. Although absolute craving level can predict smoking behavior,
      smoking cue reactivity per se may not predict cessation outcome. METHODS: All
      clinical trials of cue reactivity and cessation outcome published before 2007
      were identified and supplemented with a web-based search of clinical studies
      published after 2006, producing one additional trial. Examined were a total of 6
      studies that directly related self-reported craving in response to laboratory
      presented smoking cues with subsequent ability to quit smoking. RESULTS: Of the 6
      studies, only one found that lower cue reactivity predicted greater quitting
      success (with nicotine but not placebo patch). Another study found the opposite,
      that higher cue reactivity was related to greater, rather than less, quitting
      success (in an unaided attempt). The other studies showed no association between
      cue reactivity and cessation outcome. CONCLUSIONS: This limited research does not
      clearly support self-reported craving in response to smoking cues per se as a
      predictor of later quitting success. Lack of consistent results may partly be due
      to variability in methods of smoking cue assessment, type of cessation treatment,
      and duration of follow-up assessment. If it is to improve our understanding of an
      individual's ability to quit smoking, research on cue reactivity needs to show
      significant and reliable associations with subsequent long-term smoking behavior.

PMID- 22140148
TI  - Setting a good example? Changes in smoking prevalence among key occupational
      groups in New Zealand: evidence from the 1981 and 2006 censuses.
AB  - INTRODUCTION: Role modeling by smokers may influence smoking among children and
      young adults. Most work on smoking by occupation has focused on health workers. A
      unique opportunity to explore smoking by occupation is presented in New Zealand
      (NZ) due to inclusion of a smoking status question in most national censuses
      since 1976. Our aim was to assess trends in smoking prevalence among potential
      role model occupational groups in NZ. METHODS: Adult smoking status by occupation
      was obtained from the 1981 census (N = 1,321,323) and 2006 census (N =
      1,744,479). Subjects were aggregated into 5 broad groups of potential role-model
      occupations: teachers, uniformed services, health-related occupations, public
      figures, and sportspeople/entertainers. Age and sex-standardized current smoking
      prevalences were calculated using the 2006 NZ employed population as the
      reference standard. RESULTS: Standardized smoking prevalence among the employed
      population was 34.5% in 1981 and had declined 37% in relative terms and 12.8% in
      absolute terms to 21.7% in 2006. Relative declines in smoking prevalence between
      1981 and 2006 ranged from 35% to 60% among the role model occupational groups and
      absolute declines from 8.3% to 19.9%. Maori had higher smoking prevalence and
      lower relative declines in prevalence in each occupational group from 1981 to
      2006, compared with non-Maori. Specific occupations mostly had low smoking
      prevalences--particularly doctors and teachers. But some role model occupations
      had high crude smoking prevalences in 2006 (up to 47%). CONCLUSIONS: Persisting
      high smoking prevalence among some occupational groups suggest that additional
      targeted smoking cessation support for role model occupational groups may be
      justified.

PMID- 22140149
TI  - Patterns of water-pipe and cigarette smoking initiation in schoolchildren: Irbid
      longitudinal smoking study.
AB  - INTRODUCTION: Tobacco use remains a major public health problem worldwide. Water
      pipe smoking is spreading rapidly and threatening to undermine the successes
      achieved in tobacco control. METHODS: A school-based longitudinal study in the
      city of Irbid, Jordan, was performed from 2008 to 2010. All seventh-grade
      students in 19 randomly selected schools, out of a total of 60 schools in the
      city, were enrolled at baseline and surveyed annually. RESULTS: Of the 1781
      students enrolled at baseline 1,701 (95.5%) were still in the study at the end of
      the second year of follow-up (869 boys, median age at baseline 13 years). Ever
      and current water-pipe smoking were higher than those of cigarette smoking at
      baseline (ever smoking: 25.9% vs. 17.6% and current smoking: 13.3% vs. 5.3% for
      water-pipe and cigarette smoking, respectively; p < .01 for both) but cigarette
      smoking caught up by the second year of follow-up (ever smoking: 46.4% vs. 44.7%;
      p = .32 and current smoking: 18.9% vs. 14.9%; p < .01). Water pipe-only smokers
      at baseline were twice as likely to become current cigarette smokers after 2
      years compared with never smokers (relative risk (RR) = 2.1; 95% CI = 1.2, 3.4).
      A similar pattern was observed for cigarette-only smokers at baseline (RR = 2.0;
      95% CI = 0.9, 4.8). CONCLUSIONS: Prevalence of water-pipe and cigarette smoking
      increased dramatically over the 2-year follow-up period with similar patterns in
      boys and girls, although girls had lower prevalence in all categories. Water-pipe
      smoking at baseline predicted the progress to cigarette smoking in the future and
      vice versa.

PMID- 22140150
TI  - Magnetospira thiophila gen. nov., sp. nov., a marine magnetotactic bacterium that
      represents a novel lineage within the Rhodospirillaceae (Alphaproteobacteria).
AB  - A marine, magnetotactic bacterium, designated strain MMS-1(T), was isolated from
      mud and water from a salt marsh in Woods Hole, Massachusetts, USA, after
      enrichment in defined oxygen-concentration/redox-gradient medium. Strain MMS-1(T)
      is an obligate microaerophile capable of chemoorganoheterotrophic and
      chemolithoautotrophic growth. Optimal growth occurred at pH 7.0 and 24-26 
      degrees C. Chemolithoautotrophic growth occurred with thiosulfate as the electron
      donor and autotrophic carbon fixation was via the Calvin-Benson-Bassham cycle.
      The G+C content of the DNA of strain MMS-1(T) was 47.2 mol%. Cells were Gram
      negative and morphologically variable, with shapes that ranged from that of a
      lima bean to fully helical. Cells were motile by means of a single flagellum at
      each end of the cell (amphitrichous). Regardless of whether grown in liquid or
      semi-solid cultures, strain MMS-1(T) displayed only polar magnetotaxis and
      possessed a single chain of magnetosomes containing elongated octahedral crystals
      of magnetite, positioned along the long axis of the cell. Phylogenetic analysis
      based on 16S rRNA gene sequences indicated that strain MMS-1(T) belongs to the
      family Rhodospirillaceae within the Alphaproteobacteria, and is distantly related
      to species of the genus Magnetospirillum. Strain MMS-1(T) is therefore considered
      to represent a novel species of a new genus, for which the name Magnetospira
      thiophila gen. nov., sp. nov. is proposed. The type strain of Magnetospira
      thiophila is MMS-1(T) ( = ATCC BAA-1438(T) = JCM 17960(T)).

PMID- 22140151
TI  - Phorcysia thermohydrogeniphila gen. nov., sp. nov., a thermophilic,
      chemolithoautotrophic, nitrate-ammonifying bacterium from a deep-sea hydrothermal
      vent.
AB  - A novel hyperthermophilic, anaerobic, chemolithoautotrophic bacterium, designated
      strain HB-8(T), was isolated from the tube of Alvinella pompejana tubeworms
      collected from the wall of an actively venting sulfide structure on the East
      Pacific Rise at 13 degrees  N. The cells were Gram-negative rods, approximately
      1.0-1.5 um long and 0.5 um wide. Strain HB-8(T) grew between 65 and 80  degrees C
      (optimum 75  degrees C), 15 and 35 g NaCl l(-1) (optimum 30 g l(-1)) and pH 4.5
      and 8.5 (optimum pH 6.0). Generation time under optimal conditions was 26 min.
      Growth occurred under chemolithoautotrophic conditions with H(2) as the energy
      source and CO(2) as the carbon source. Nitrate and sulfur were used as electron
      acceptors, with concomitant formation of ammonium or hydrogen sulfide,
      respectively. The presence of lactate, formate, acetate or tryptone in the
      culture medium inhibited growth. The G+C content of the genomic DNA was 47.8
      mol%. Phylogenetic analysis of the 16S rRNA gene and of the alpha subunit of the
      ATP citrate lyase of strain HB-8(T) indicated that this organism formed a novel
      lineage within the class Aquificae, equally distant from the type strains of the
      type species of the three genera that represent the family Desulfurobacteriaceae:
      Thermovibrio ruber ED11/3LLK8(T), Balnearium lithotrophicum 17S(T) and
      Desulfurobacterium thermolithotrophum BSA(T). The polar lipids of strain HB-8(T)
      differed substantially from those of other members of the Desulfurobacteriaceae,
      and this bacterium produced novel quinones. On the basis of phylogenetic,
      physiological and chemotaxonomic characteristics, it is proposed that the
      organism represents a novel genus and species within the family
      Desulfurobacteriaceae, Phorcysia thermohydrogeniphila gen. nov., sp. nov. The
      type strain of Phorcysia thermohydrogeniphila is HB-8(T) ( = DSM 24425(T)  = JCM
      17384(T)).

PMID- 22140152
TI  - Anaerosalibacter bizertensis gen. nov., sp. nov., a halotolerant bacterium
      isolated from sludge.
AB  - A strictly anaerobic, halotolerant and thermotolerant strain, designated
      C5BEL(T), was isolated in north Tunisia from storage tanks holding waste
      generated by the recycling of discarded motor oils. Cells of strain C5BEL(T) were
      Gram-stain-positive, motile by laterally inserted flagella, straight, and spore
      forming. Their two major fatty acids were iso-C(15 : 0) and iso-C(15 : 0)
      dimethyl acetal. Growth was observed at temperatures of 25-55  degrees C
      (optimum, 40  degrees C) and at pH 6-9 (optimum, pH 7.5). The salinity range for
      growth was 0-100 g l(-1) NaCl (optimum, 5 g l(-1)). Yeast extract was required
      for growth. Strain C5BEL(T) was heterotrophic, able to use glucose, pyruvate,
      succinate, yeast extract, bio-trypticase and peptone, but unable to grow on
      Casamino acids. Sulfate, thiosulfate, sulfite, elemental sulfur, fumarate,
      nitrate and nitrite were not reduced. The DNA G+C content of strain C5BEL(T) was
      31.1 mol%. 16S rRNA gene sequence analysis indicated that strain C5BEL(T) was a
      member of the family Clostridiaceae, class Clostridia, phylum Firmicutes and was
      most closely related to Sporanaerobacter acetigenes Lup33(T) ( = DSM 13106(T))
      (92.4 % similarity). On the basis of 16S rRNA gene sequence comparisons and
      physiological characteristics, strain C5BEL(T) can be classified as a novel
      species in a new genus, for which the name Anaerosalibacter bizertensis gen.
      nov., sp. nov. is proposed. The type strain of the type species is C5BEL(T) ( =
      DSM 23801(T) = JCM 17239(T)).

PMID- 22140153
TI  - Plantactinospora endophytica sp. nov., an actinomycete isolated from Camptotheca
      acuminata Decne., reclassification of Actinaurispora siamensis as
      Plantactinospora siamensis comb. nov. and emended descriptions of the genus
      Plantactinospora and Plantactinospora mayteni.
AB  - A novel endophytic actinomycete, designated strain YIM 68255(T), was isolated
      from healthy leaves of Camptotheca acuminata Decne. collected in Yunnan province,
      south-west China and characterized by using a polyphasic approach. The strain
      formed well-developed substrate mycelium, but no aerial mycelium. It grew at 10
      45  degrees C, at pH 5-10 (optimum pH 7) and in the presence of 0-3 % (w/v) NaCl.
      The DNA G+C content was 73.0 mol%. Phylogenetic analyses showed that strain YIM
      68255(T) belonged to the genus Plantactinospora. However, it exhibited some
      differences from Plantactinospora mayteni YIM 61359(T) and the level of DNA-DNA
      relatedness was 42.7 +/- 1.3 %. Based on comparative analysis of physiological
      and chemotaxonomic data, it is proposed that strain YIM 68255(T) represents a
      novel species of the genus Plantactinospora, Plantactinospora endophytica sp.
      nov., with strain YIM 68255(T) ( = DSM 45387(T) = CCTCC AA 209047(T)) as the type
      strain. In addition, it is also proposed that Actinaurispora siamensis Thawai et
      al. 2010 be transferred to the genus Plantactinospora as Plantactinospora
      siamensis comb. nov. [type strain CM2-8(T) ( = JCM 15677(T) = BCC 34762(T))]
      based on chemotaxonomic characteristics and phylogenetic analysis. Emended
      descriptions of the genus Plantactinospora and Plantactinospora mayteni are also
      provided.

PMID- 22140154
TI  - Cryptosporangium mongoliense sp. nov., isolated from soil.
AB  - A Gram-positive, aerobic, non-motile actinomycete, strain MN08-A0264(T), was
      isolated from soil sampled in Mongolia. The isolate formed pale to moderate
      yellowish brown colonies and branched substrate mycelium. On the basis of 16S
      rRNA gene sequence analysis, strain MN08-A0264(T) belonged to the genus
      Cryptosporangium and exhibited 97.9 % 16S rRNA gene sequence similarity with
      Cryptosporangium aurantiacum IMSNU 22120(T), 97.7 % with C. minutisporangium IFO
      15962(T), 97.2 % with C. arvum IFO 15965(T) and 96.8 % with C. japonicum IFO
      15966(T). The allocation of the isolate to the genus Cryptosporangium was
      supported by chemotaxonomic data: menaquinone MK-9(H(6)) with minor amounts of MK
      9(H(8)) and MK-9(H(4)), major amounts of iso-C(16 : 0), C(18 : 1)9c and C(17 : 0)
      10-methyl, a polar lipid profile comprising phosphatidylethanolamine,
      phosphatidylinositol, diphosphatidylglycerol, phosphatidylglycerol and
      glycolipids, and whole-cell sugars glucose, galactose, acofriose (3-0
      methylrhamnose), mannose, ribose, arabinose, xylose and rhamnose (trace). DNA-DNA
      relatedness (5-20 %) differentiated the isolate from its closest neighbours. The
      physiological and biochemical tests allowed the differentiation of strain MN08
      A0264(T) from members of the genus Cryptosporangium. Thus, strain MN08-A0264(T)
      represents a novel species, for which the name Cryptosporangium mongoliense sp.
      nov. is proposed. The type strain is MN08-A0264(T) ( = NBRC 105887(T)  = VTCC D9
      27(T)).

PMID- 22140155
TI  - Brevundimonas viscosa sp. nov., isolated from saline soil.
AB  - A Gram-negative, rod-shaped bacterial strain, designated F3(T), was isolated from
      a saline soil sample in China and studied by using a polyphasic taxonomic
      approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that
      strain F3(T) was affiliated with the genus Brevundimonas, with Brevundimonas
      kwangchunensis KSL-102(T) (98.4 % similarity) and Brevundimonas alba DSM 4736(T)
      (98.2 %) as its closest relatives. Strain F3(T) contained ubiquinone-10 (Q-10) as
      the predominant ubiquinone and C(18 : 1)omega7c, C(17 : 1)omega8c and C(16 : 0)
      as the major fatty acids. The DNA G+C content of strain F3(T) was 66.7 mol%.
      Levels of DNA-DNA relatedness between strain F3(T) and the type strains of
      closely related Brevundimonas species were below 22 %. On the basis of phenotypic
      characteristics and genotypic distinctiveness, strain F3(T) should be classified
      as representing a novel species of the genus Brevundimonas, for which the name
      Brevundimonas viscosa sp. nov. is proposed. The type strain is F3(T) ( = CGMCC
      1.10683(T) = JCM 17426(T)).

PMID- 22140156
TI  - Delftia litopenaei sp. nov., a poly-beta-hydroxybutyrate-accumulating bacterium
      isolated from a freshwater shrimp culture pond.
AB  - A Gram-negative, short-rod-shaped, motile, non-spore-forming and poly-beta
      hydroxybutyrate-accumulating bacterial strain, designated wsw-7(T), was isolated
      from a freshwater shrimp culture pond in Taiwan and was characterized using a
      polyphasic taxonomic approach. Phylogenetic analyses based on 16S rRNA gene
      sequences showed that the closest relatives of strain wsw-7(T) were Delftia
      lacustris 332(T), Delftia tsuruhatensis T7(T) and Delftia acidovorans ATCC
      15668(T), with sequence similarities of 98.5, 98.4 and 97.9%, respectively.
      Phylogenetic trees obtained with 16S rRNA gene sequences or the
      polyhydroxyalkanoate synthase (phaC) gene sequences revealed that strain wsw-7(T)
      and these three closest relatives formed an independent phylogenetic clade within
      the order Burkholderiales. Strain wsw-7(T) contained summed feature 3 (comprising
      C(16:1)omega7c and/or C(16:1)omega6c), C(18:0) and C(18:1)omega7c as predominant
      fatty acids. The major isoprenoid quinone was Q-8 and the DNA G+C content was
      67.6 mol%. The polar lipid profile consisted of a mixture of
      phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, an
      uncharacterized aminolipid and several uncharacterized phospholipids. On the
      basis of the genotypic, chemotaxonomic and phenotypic data, strain wsw-7(T)
      represents a novel species in the genus Delftia, for which the name Delftia
      litopenaei sp. nov. is proposed; the type strain is wsw-7(T) ( = BCRC 80212(T) =
      LMG 25724(T)).

PMID- 22140157
TI  - Herbidospora mongoliensis sp. nov., isolated from soil, and reclassification of
      Herbidospora osyris and Streptosporangium claviforme as synonyms of Herbidospora
      cretacea.
AB  - A Gram-reaction-positive aerobic actinomycete, designated strain MN08-A0118(T),
      which produced short chains of non-motile spores on the tips of long sporophores
      and formed yellow-brown colonies with branched substrate mycelium, was studied in
      detail to determine its taxonomic position. On the basis of 16S rRNA gene
      sequence analyses, strain MN08-A0118(T) was grouped into the genus Herbidospora,
      being most closely related to Streptosporangium claviforme (98.2%), Herbidospora
      osyris (98.2%), Herbidospora daliensis (98.2%), Herbidospora cretacea (97.9%) and
      Herbidospora yilanensis (97.4%). Chemotaxonomic data supported allocation of the
      strain to the genus Herbidospora. MK-10(H(4)) was the predominant menaquinone
      with minor amounts of MK-10(H(6)), MK-10(H(2)) and MK-9(H(4)); the fatty acid
      profile contained major amounts of iso-C(16:0), C(17:0) 10-methyl, iso-C(14:0)
      and iso-C(16:0) 2-OH; the phospholipid profile contained
      phosphatidylethanolamine, phosphatidylmethylethanolamine and glucosamine
      containing phospholipids; and the whole-cell sugars included ribose, glucose,
      galactose, madurose and rhamnose (trace). The phylogenetic data, phenotypic and
      genotypic properties and DNA-DNA hybridization differentiated this strain from
      its closely related strains, S. claviforme (35-54% DNA-DNA relatedness), H.
      osyris (39-51%), H. daliensis (3-16%), H. cretacea (34-39%) and H. yilanensis (34
      42%). Thus, MN08-A0118(T) represents a novel species of the genus Herbidospora,
      for which the name Herbidospora mongoliensis sp. nov. is proposed, with MN08
      A0118(T) ( = NBRC 105882(T)  = VTCC D9-22(T)) as the type strain. In addition,
      DNA-DNA hybridization results showed that S. claviforme and H. osyris are
      synonyms of H. cretacea.

PMID- 22140158
TI  - Cellulosibacter alkalithermophilus gen. nov., sp. nov., an anaerobic
      alkalithermophilic, cellulolytic-xylanolytic bacterium isolated from soil of a
      coconut garden.
AB  - An obligately anaerobic, cellulolytic-xylanolytic bacterium, designated strain
      A6(T), was isolated from soil of a coconut garden in the Bangkuntien district of
      Bangkok, Thailand. The strain was Gram-stain positive, catalase-negative,
      endospore-forming, motile and rod-shaped with a cell size of 0.2-0.3*2.0-3.0 um.
      Optimal growth of strain A6(T) occurred at pH(55  degrees C) 9.5, 55  degrees C.
      Strain A6(T) fermented various carbohydrates, and the end products from the
      fermentation of cellobiose were acetate, ethanol, propionate and a small amount
      of butyrate. The major cellular fatty acids were iso-C(14:0) 3-OH, iso-C(15:0),
      iso-C(16:0) and C(16:0). The cell-wall peptidoglycan contained meso
      diaminopimelic acid. No respiratory quinones were detected. The DNA G+C content
      was 30.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed
      that the strain represented a new phyletic sublineage within the family
      Clostridiaceae, with <93.0% 16S rRNA gene sequence similarity to recognized
      species of this family. On the basis of phenotypic, genotypic and physiological
      evidence, strain A6(T) represents a novel species of a new genus, for which the
      name Cellulosibacter alkalithermophilus gen. nov., sp. nov. is proposed. The type
      strain of the type species is A6(T) ( = TISTR 1915(T) = KCTC 5874(T)).

PMID- 22140159
TI  - Peptoniphilus duerdenii sp. nov. and Peptoniphilus koenoeneniae sp. nov.,
      isolated from human clinical specimens.
AB  - Two previously uncharacterized strains of Gram-reaction-positive, anaerobic,
      coccus-shaped bacteria, designated strains WAL 18896(T) and WAL 18898(T), were
      recovered from human wound specimens and characterized using phenotypic,
      chemotaxonomic and molecular taxonomic methods. Comparative 16S rRNA gene
      sequence analysis and chemotaxonomic and biochemical characteristics demonstrated
      that these organisms are genotypically and phenotypically distinct and represent
      previously unidentified sublines within the order Clostridiales in the phylum
      Firmicutes. Pairwise sequence analysis demonstrated that the novel organisms had
      91.9% sequence similarity to each other and were most closely related to members
      of the genus Peptoniphilus. The major long-chain fatty acids of both strains were
      C(16:0,) C(18:0), C(18:1)omega9c and C(18:2)omega6,9c. Based on the phenotypic
      and phylogenetic findings, strains WAL 18896(T) ( = CCUG 56065(T)  = ATCC BAA
      1640(T)) and WAL 18898(T) ( = CCUG 56067(T)  = ATCC BAA-1638(T)  = DSM 22616(T))
      represent two novel species, for which the names Peptoniphilus duerdenii sp. nov.
      and Peptoniphilus koenoeneniae sp. nov. are proposed, respectively.

PMID- 22140160
TI  - Massilia tieshanensis sp. nov., isolated from mining soil.
AB  - A bacterial isolate, designated strain TS3(T), was isolated from soil collected
      from a metal mine in Tieshan District, Daye City, Hubei Province, in central
      China. Cells of this strain were Gram-negative, motile and rod-shaped. The strain
      had ubiquinone Q-8 as the predominant respiratory quinone,
      phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol as the
      major polar lipids and summed feature 3 (C(16:1)omega7c and/or iso-C(15:0) 2-OH),
      C(16:0) and C(18:1)omega7c as the major fatty acids. The G+C content was 65.9
      mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain
      TS3(T) was most closely related to Massilia niastensis 5516S-1(T) (98.5%),
      Massilia consociata CCUG 58010(T) (97.6%), Massilia aerilata 5516S-11(T) (97.4%)
      and Massilia varians CCUG 35299(T) (97.2%). DNA-DNA hybridization revealed low
      relatedness between strain TS3(T) and M. niastensis KACC 12599(T) (36.5%), M.
      consociata CCUG 58010(T) (27.1%), M. aerilata KACC 12505(T) (22.7%) and M.
      varians CCUG 35299(T) (46.5%). On the basis of phenotypic and phylogenetic
      characteristics, strain TS3(T) belongs to the genus Massilia, but is clearly
      differentiated from other members of the genus. The strain represents a novel
      species, for which the name Massilia tieshanensis sp. nov. is proposed. The type
      strain is TS3(T) ( = CCTCC AB 2010202(T)  = KACC 14940(T)).

PMID- 22140161
TI  - Streptomyces glycovorans sp. nov., Streptomyces xishensis sp. nov. and
      Streptomyces abyssalis sp. nov., isolated from marine sediments.
AB  - Strains YIM M 10366(T), YIM M 10378(T) and YIM M 10400(T) were isolated from
      marine sediments collected from the Xisha Islands in the South China Sea. All
      three isolates were able to grow optimally at pH 7.0, 28-37  degrees C and 0-3%
      (w/v) NaCl. Comparison of 16S rRNA gene sequences showed that these strains are
      members of the genus Streptomyces, exhibiting moderately high 16S rRNA gene
      sequence similarities of 97.0-98.8% to members of the most closely related
      Streptomyces species. Morphological characteristics, physiological
      characteristics and compositions of whole-cell sugars and phospholipids are
      consistent with the diagnostic characteristics of the genus Streptomyces, but
      still allowed differentiation amongst the three strains and their neighbours.
      Based on 16S rRNA gene sequence analysis, DNA-DNA relatedness, phenotypic
      characteristics and chemotaxonomic data, strains YIM M 10366(T), YIM M 10378(T)
      and YIM M 10400(T) were identified as members of three novel species of the genus
      Streptomyces, for which the names Streptomyces glycovorans sp. nov. (type strain
      YIM M 10366(T)  =DSM 42021(T)  =CCTCC AA2010005(T)), Streptomyces xishensis sp.
      nov. (type strain YIM M 10378(T)  = DSM 42022(T)  =CCTCC AA 2010006(T)) and
      Streptomyces abyssalis sp. nov. (type strain YIM M 10400(T)  =DSM 42024(T)  =
      CCTCC AA 2010008(T)) are proposed.

PMID- 22140162
TI  - Flavobacterium dankookense sp. nov., isolated from a freshwater reservoir, and
      emended descriptions of Flavobacterium cheonanense, F. chungnamense, F. koreense
      and F. aquatile.
AB  - A novel yellow-pigmented bacterial strain, designated ARSA-19(T), was isolated
      from a freshwater reservoir in Cheonan, Korea. Cells were Gram-staining-negative,
      rod-shaped, strictly aerobic and positive for catalase and oxidase. The
      phylogenetic tree based on 16S rRNA gene sequences showed that strain ARSA-19(T)
      belonged to the genus Flavobacterium and was related to Flavobacterium
      macrobrachii an-8(T) (96.5% sequence similarity), F. koreense KACC 14969(T)
      (96.2%), F. chungnamense KACC 14971(T) (96.1%), F. cheonanense KACC 14972(T)
      (96.4%) and F. aquatile ATCC 11947(T) (95.6%). The isolate contained MK-6 as the
      predominant menaquinone and iso-C(15:0) (21.8%), iso-C(16:0) 3-OH (10.4%), iso
      C(15:1) G (9.3%), summed feature 3 (iso-C(15:0) 2-OH and/or C(16:1)omega7c;
      8.2%), iso-C(15:0) 3-OH (7.7%) and iso-C(16:0) (7.3%) as the major fatty acids.
      The polar lipids of strain ARSA-19(T) were phosphatidylethanolamine, four unknown
      aminolipids and two unidentified polar lipids. The DNA G+C content of strain ARSA
      19(T) was 33.3 mol%. Based on its phenotypic and genotypic characteristics and on
      the phylogenetic evidence presented, strain ARSA-19(T) is considered to represent
      a novel species in the genus Flavobacterium, for which the name Flavobacterium
      dankookense sp. nov. is proposed. The type strain is ARSA-19(T) ( = KCTC 23179(T)
      = JCM 17065(T)  = KACC 14968(T)). Emended descriptions of Flavobacterium
      cheonanense, Flavobacterium chungnamense, Flavobacterium koreense and
      Flavobacterium aquatile are also proposed.

PMID- 22140163
TI  - Description of Lysinibacillus sinduriensis sp. nov., and transfer of Bacillus
      massiliensis and Bacillus odysseyi to the genus Lysinibacillus as Lysinibacillus
      massiliensis comb. nov. and Lysinibacillus odysseyi comb. nov. with emended
      description of the genus Lysinibacillus.
AB  - A Gram-positive, rod-shaped, endospore-forming bacterium, designated strain BLB
      1(T), was isolated from samples of tidal flat sediment from the Yellow Sea. 16S
      rRNA gene sequence analysis demonstrated that the isolate belonged to the
      Bacillus rRNA group 2 and was closely related to Bacillus massiliensis CIP
      108446(T) (97.4%), Bacillus odysseyi ATCC PTA-4993(T) (96.7%), Lysinibacillus
      fusiformis DSM 2898(T) (96.2%) and Lysinibacillus boronitolerans DSM 17140(T)
      (95.9%). Sequence similarities with related species in other genera, including
      Caryophanon, Sporosarcina and Solibacillus, were <96.1%. Chemotaxonomic data
      supported the affiliation of strain BLB-1(T) with the genus Lysinibacillus. The
      major menaquinone was MK-7, the cell-wall sugars were glucose and xylose, the
      cell-wall peptidoglycan type was A4alpha (L-Lys-D-Asp), the major polar lipids
      were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and
      several unknown phospholipids, and the major fatty acids were anteiso-C(15:0)
      (35.6%), iso-C(15:0) (25.6%) and anteiso-C(17:0) (16.5%). The most closely
      related species, Bacillus massiliensis and Bacillus odysseyi, were also assigned
      to this genus based on phylogenetic analysis and phenotypic data. The results of
      DNA-DNA hybridizations and phenotypic tests supported the differentiation of all
      three taxa from species of the genus Lysinibacillus with validly published names.
      Thus, strain BLB-1(T) ( = KCTC 13296(T)  = JCM 15800(T)) represents a novel
      species, for which the name Lysinibacillus sinduriensis sp. nov. is proposed. It
      is also proposed that Bacillus massiliensis CIP 108446(T) ( =4400831(T) =
      CCUG49529(T)  =KCTC 13178(T)) and Bacillus odysseyi NBRC 100172(T) ( =34hs-1(T) 
      =ATCC PTA-4993(T)  =NRRL B-30641(T)  =DSM 18869(T)  =CIP 108263(T)  =KCTC
      3961(T)) be transferred to the genus Lysinibacillus as Lysinibacillus
      massiliensis comb. nov. and Lysinibacillus odysseyi comb. nov., respectively.

PMID- 22140164
TI  - Lentzea jiangxiensis sp. nov., isolated from acidic soil.
AB  - A novel actinomycete, designated strain FXJ1.034(T), was isolated from acidic
      soil collected in Jiangxi Province, South-east China. Phylogenetic analysis based
      on 16S rRNA gene sequences indicated that strain FXJ1.034(T) belonged to the
      genus Lentzea and showed high sequence similarities to Lentzea kentuckyensis NRRL
      B-24416(T) (98.5%) and Lentzea albida NBRC 16102(T) (98.3%). Morphological and
      chemotaxonomic characteristics supported its assignment to the genus Lentzea. The
      results of DNA-DNA hybridization, physiological and biochemical tests allowed
      genotypic and phenotypic differentiation of the novel strain from closely related
      species. Based on the evidence presented here, strain FXJ1.034(T) represents a
      novel species of the genus Lentzea, for which the name Lentzea jiangxiensis sp.
      nov. is proposed. The type strain is FXJ1.034(T) ( = CGMCC 4.6609(T)  = NBRC
      106680(T)).

PMID- 22140165
TI  - Pseudonocardia xishanensis sp. nov., an endophytic actinomycete isolated from the
      roots of Artemisia annua L.
AB  - A Gram-positive, non-motile, endophytic actinomycete, designated strain YIM
      63638(T), was isolated from the surface-sterilized roots of Artemisia annua L.
      The isolate grew optimally with 1-3 % (w/v) NaCl, at pH 6.0-7.0 and at 20-37 
      degrees C. Comparative analysis of the 16S rRNA gene sequence showed that the
      isolate belonged to the genus Pseudonocardia and showed highest sequence
      similarity with Pseudonocardia oroxyli D10(T) (98.9 %), Pseudonocardia
      ailaonensis YIM 45505(T) (98.3 %) and Pseudonocardia halophobica IMSNU 21327(T)
      (98.0 %). Phylogenetic distance from other type strains of species with validly
      published names within the genus Pseudonocardia was greater than 2.3 %. Strain
      YIM 63638(T) had a genomic DNA G+C content of 72.1 mol% and MK-8(H(4)) as the
      predominant respiratory quinone. The major fatty acids were iso-C(16 : 0) (36.32
      %) and 10-methyl-C(16 : 0) (19.78 %). On the basis of phenotypic properties and
      phylogenetic distinctiveness, strain YIM 63638(T) represents a novel species of
      the genus Pseudonocardia, for which the name Pseudonocardia xishanensis sp. nov.
      is proposed. The type strain is YIM 63638(T) ( = JCM 17906(T)  = KCTC 29005(T)).

PMID- 22140166
TI  - Reclassification of Lactobacillus kimchii and Lactobacillus bobalius as later
      subjective synonyms of Lactobacillus paralimentarius.
AB  - Characterization and identification of strain CW 1 ( = JCM 17161) isolated from
      corn silage were performed. Strain CW 1 was a Gram-positive, catalase-negative
      and homofermentative rod that produced the DL-form of lactic acid. This strain
      exhibited more than 99.6% 16S rRNA gene sequence similarity and greater than 82%
      DNA-DNA reassociation with type strains of Lactobacillus kimchii, L. bobalius and
      L. paralimentarius. To clarify the taxonomic positions of these type strains,
      phenotypic characterization, 16S rRNA gene sequencing, ribotyping and DNA-DNA
      relatedness were examined. The three type strains displayed different L
      arabinose, lactose, melibiose, melezitose, raffinose and N-acetyl-beta
      glucosaminidase fermentation patterns. Phylogenetic analysis showed that L.
      paralimentarius is a closer neighbour of L. kimchii and L. bobalius, sharing 99.5
      99.9% 16S rRNA gene sequence similarity, which was confirmed by the high DNA-DNA
      relatedness (>=82%) between L. paralimentarius JCM 10415(T), L. bobalius JCM
      16180(T) and L. kimchii JCM 10707(T). Therefore, it is proposed that L. kimchii
      and L. bobalius should be reclassified as later synonyms of L. paralimentarius.

PMID- 22140167
TI  - Gryllotalpicola gen. nov., with descriptions of Gryllotalpicola koreensis sp.
      nov., Gryllotalpicola daejeonensis sp. nov. and Gryllotalpicola kribbensis sp.
      nov. from the gut of the African mole cricket, Gryllotalpa africana, and
      reclassification of Curtobacterium ginsengisoli as Gryllotalpicola ginsengisoli
      comb. nov.
AB  - Strains RU-16(T), RU-28, RU-04(T) and PU-02(T) were isolated from the gut of the
      African mole cricket, Gryllotalpa africana. Phylogenetic analyses based on 16S
      rRNA gene sequences revealed that the strains belonged to the family
      Microbacteriaceae. All four strains were most closely related to Curtobacterium
      ginsengisoli DCY26(T) (below 97% 16S rRNA gene sequence similarity). These
      isolates were Gram-stain-positive, motile (by gliding), rod-shaped and exhibited
      ivory-coloured colonies. Their chemotaxonomic properties included MK-11 as the
      major respiratory quinone, ornithine as the cell-wall diamino acid, acetyl as the
      acyl type of the peptidoglycan, cyclohexyl-C(17:0) as the major fatty acid and
      phosphatidylglycerol and diphosphatidylglycerol as the major polar lipids. On the
      basis of phenotypic, chemotaxonomic and phylogenetic analyses, we propose a new
      genus in the family Microbacteriaceae, Gryllotalpicola gen. nov., with three
      novel species, Gryllotalpicola daejeonensis sp. nov. (type strain RU-04(T)  =KCTC
      13809(T)  =JCM 17590(T)), Gryllotalpicola koreensis sp. nov. (type strain RU
      16(T)  = KCTC 13810(T)  =JCM 17591(T)) and Gryllotalpicola kribbensis sp. nov.
      (type strain PU-02(T)  =KCTC 13808(T)  =JCM 17593(T)). Gryllotalpicola koreensis
      is the type species of the genus. Additionally, we propose that Curtobacterium
      ginsengisoli should be reclassified in the genus as Gryllotalpicola ginsengisoli
      comb. nov. (type strain DCY26(T)  =KCTC 13163(T)  = JCM 14773(T)).

PMID- 22140168
TI  - Georgenia satyanarayanai sp. nov., an alkaliphilic and thermotolerant amylase
      producing actinobacterium isolated from a soda lake.
AB  - A Gram-stain-positive, oxidase-negative, starch-hydrolysing, actinobacterium
      (strain JC82(T)) was isolated from a soda lake in Lonar, India. Based on 16S rRNA
      gene sequence similarity studies, strain JC82(T) belonged to the genus Georgenia
      and was most closely related to Georgenia muralis 1A-C(T) (96.8 %) and other
      members of the genus Georgenia (<96.5 %). The DNA G+C content of strain JC82(T)
      was 73.4 mol%. The cell-wall amino acids were alanine, glutamic acid and lysine
      with peptidoglycan type A4alpha. Polar lipids included diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, an
      unidentified lipid (L1) and an unidentified glycolipid (GL3). The predominant
      isoprenoid quinone was menaquinone MK-8(H(4)). Anteiso-C(15 : 0) was the
      predominant fatty acid and significant proportions of iso-C(14 : 0), C(14 : 0),
      C(16 : 0), iso-C(15 : 0) and iso-C(16 : 0) were also detected. Strain JC82(T)
      produced thermostable alkaline amylase. The results of physiological and
      biochemical tests allowed a clear phenotypic differentiation of strain JC82(T)
      from all other members of the genus Georgenia. Based on these data, strain
      JC82(T) represents a novel species of the genus Georgenia, for which the name
      Georgenia satyanarayanai sp. nov. is proposed. The type strain is JC82(T) ( =
      KCTC 19802(T) = NBRC 107612(T)).

PMID- 22140169
TI  - Conexibacter arvalis sp. nov., isolated from a cultivated field soil sample.
AB  - Two bacterial strains, designated KV-962(T) and KV-963, were isolated from soil
      collected from a field in Japan. Cells of both strains were Gram-staining
      positive, non-spore-forming, short rod-shaped and motile. Phylogenetic analysis
      based on 16S rRNA gene sequences indicated that these strains were related to
      Conexibacter woesei DSM 14684(T), with a similarity value of 98.6 %. These
      strains possessed MK-7 (H(4)) as the sole menaquinone and contained C(18 :
      1)omega9c, C(17 : 1)omega6c and iso-C(16 : 0) as the major fatty acids. On the
      basis of genotypic and phenotypic characteristics, strain KV-962(T) and KV-963
      were indicated as a novel species of the genus Conexibacter, for which the name
      Conexibacter arvalis sp. nov. is proposed. The type strain is KV-962(T) ( = DSM
      23288(T)  = NBRC 106558(T)).

PMID- 22140170
TI  - Compostimonas suwonensis gen. nov., sp. nov., isolated from spent mushroom
      compost.
AB  - A Gram-positive, aerobic, non-motile, short rod, designated SMC46(T), was
      isolated from a spent mushroom compost sample collected in the Suwon region,
      South Korea. 16S rRNA gene sequence analysis revealed that strain SMC46(T) was a
      member of the family Microbacteriaceae; however, the isolate formed a branch
      separate from other genera within the family. Sequence similarity between strain
      SMC46(T) and other members of the family Microbacteriaceae was <=97 %, the
      highest sequence similarity being with Frigoribacterium faeni 801(T) and
      Frondihabitans australicus E1HC-02(T) (both 97.0 %). Some chemotaxonomic
      properties of strain SMC46(T) were consistent with those of the family
      Microbacteriaceae: MK-11 and MK-12 as the predominant menaquinones, anteiso-C(15
      : 0), iso-C(16 : 0) and anteiso-C(17 : 0) as the major cellular fatty acids and
      diphosphatidylglycerol, phosphatidylglycerol and an unidentified glycolipid as
      the polar lipids. However, strain SMC46(T) contained a B-type peptidoglycan not
      previously found in the family Microbacteriaceae. The DNA G+C content was 68
      mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic
      distinctiveness, strain SMC46(T) was considered to represent a novel genus and
      species in the family Microbacteriaceae, for which the name Compostimonas
      suwonensis gen. nov., sp. nov. is proposed. The type strain of the type species
      is SMC46(T) ( = KACC 13354(T)  = NBRC 106304(T)).

PMID- 22140171
TI  - Introducing EzTaxon-e: a prokaryotic 16S rRNA gene sequence database with
      phylotypes that represent uncultured species.
AB  - Despite recent advances in commercially optimized identification systems,
      bacterial identification remains a challenging task in many routine
      microbiological laboratories, especially in situations where taxonomically novel
      isolates are involved. The 16S rRNA gene has been used extensively for this task
      when coupled with a well-curated database, such as EzTaxon, containing sequences
      of type strains of prokaryotic species with validly published names. Although the
      EzTaxon database has been widely used for routine identification of prokaryotic
      isolates, sequences from uncultured prokaryotes have not been considered. Here,
      the next generation database, named EzTaxon-e, is formally introduced. This new
      database covers not only species within the formal nomenclatural system but also
      phylotypes that may represent species in nature. In addition to an identification
      function based on Basic Local Alignment Search Tool (blast) searches and pairwise
      global sequence alignments, a new objective method of assessing the degree of
      completeness in sequencing is proposed. All sequences that are held in the
      EzTaxon-e database have been subjected to phylogenetic analysis and this has
      resulted in a complete hierarchical classification system. It is concluded that
      the EzTaxon-e database provides a useful taxonomic backbone for the
      identification of cultured and uncultured prokaryotes and offers a valuable means
      of communication among microbiologists who routinely encounter taxonomically
      novel isolates. The database and its analytical functions can be found at
      http://eztaxon-e.ezbiocloud.net/.

PMID- 22140172
TI  - Tropicimonas sediminicola sp. nov., isolated from marine sediment.
AB  - A novel Gram-negative, obligately aerobic, non-motile, rod-shaped bacterium,
      strain M97(T), was isolated from marine sediment of a cage-cultured ark clam farm
      on the south coast of Korea. Strain M97(T) was positive for oxidase and catalase.
      Optimal growth occurred at 37  degrees C, with 1-2 % (w/v) NaCl and at pH 7-8.
      The main cellular fatty acids were C(16 : 0), C(18 : 1)omega7c, C(12 : 0) 3-OH
      and cyclo-C(19 : 0)omega8c. The polar lipids comprised diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylcholine, an unknown aminolipid and three
      unknown lipids. The predominant respiratory quinone was ubiquinone-10 (Q-10).
      Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain
      M97(T) belongs to the genus Tropicimonas, with highest sequence similarity to
      Tropicimonas aquimaris DPG-21(T) (99.0 %). The DNA G+C content of strain M97(T)
      was 68.5 mol%. Mean DNA-DNA relatedness between strain M97(T) and T. aquimaris
      DPG-21(T) was 46 +/- 10 %. Based on phylogenetic, phenotypic and genotypic
      analyses, strain M97(T) is considered to represent a novel species of the genus
      Tropicimonas, for which the name Tropicimonas sediminicola sp. nov. is proposed.
      The type strain is M97(T) ( = KACC 15544(T) = JCM 17731(T)).

PMID- 22140173
TI  - Thermocatellispora tengchongensis gen. nov., sp. nov., a new member of the family
      Streptosporangiaceae.
AB  - A novel Gram-positive, aerobic, spore-forming, thermophilic actinomycete,
      designated strain YIM 77521(T), was isolated from a sandy soil sample collected
      at Rehai National Park, Tengchong, Yunnan province, south-west China. The strain
      formed branched substrate mycelia and no fragmentation was found. Masses of
      short, straight or irregular chains of three to eight warty ornamented spores
      were borne from aerial mycelia. The strain contained meso-diaminopimelic acid in
      the cell wall and the whole-cell sugars contained mannose, galactose, glucose and
      ribose. The predominant menaquinones were MK-9(H(4)), MK-9(H(6)) and MK-9(H(8)).
      The diagnostic polar lipids were diphosphatidylglycerol,
      phosphatidylmethylethanolamine, phosphatidylethanolamine,
      hydroxyphosphatidylmonomethylethanolamine and N-acetylglucosamine-containing
      phospholipids. The major fatty acids were iso-C(16 : 0), C(17 : 0) 10-methyl and
      C(18 : 0). The DNA G+C content of strain YIM 77521(T) was 73.3 mol%. Phylogenetic
      analysis based on 16S rRNA gene sequences revealed that strain YIM 77521(T) fell
      within the radiation of the suborder Streptosporangineae and formed a distinct
      monophyletic lineage adjacent to the family Streptosporangiaceae with a high
      bootstrap value. On the basis of combined data from the phenotypic and
      phylogenetic analyses, strain YIM 77521(T) represents a novel genus and species
      within the family Streptosporangiaceae, for which the name Thermocatellispora
      tengchongensis gen. nov., sp. nov. is proposed. The type strain is YIM 77521(T) (
      = DSM 45615(T)  = CCTCC AA 2011013(T)).

PMID- 22140174
TI  - Microbispora hainanensis sp. nov., isolated from rhizosphere soil of Excoecaria
      agallocha in a mangrove.
AB  - Strain 211020(T) was isolated from rhizosphere soil of Excoecaria agallocha in a
      mangrove in Hainan, China. The strain produced longitudinal pair spores branching
      from aerial hyphae. 16S rRNA gene sequence analysis showed that the isolate
      belonged to the genus Microbispora, exhibiting the highest 16S rRNA gene sequence
      similarity (98.75 %) to Microbispora corallina JCM 10267(T) with a low DNA-DNA
      relatedness value (13 +/- 0.6 %). The isolate contained meso-diaminopimelic acid
      as the diagnostic diamino acid but madurose was not detected. The predominant
      menaquinones were MK-9(H(4)), MK-9(H(2)) and MK-9(H(0)), and the major fatty
      acids were iso-C(16 : 0), iso-C(15 : 0) and C(17 : 0). The phospholipid profile
      of strain 211020(T) comprised phosphatidylinositol mannoside,
      phosphatidylethanolamine, diphosphatidylglycerol and phospholipids of unknown
      structure containing glucosamine. The DNA G+C content was 70.8 mol%. On the basis
      of phenotypic and genotypic data, strain 211020(T) can be distinguished as a
      novel species of the genus Microbispora, for which the name Microbispora
      hainanensis sp. nov., is proposed. The type strain is 211020(T) ( = CGMCC
      4.5595(T) = DSM 45428(T)).

PMID- 22140175
TI  - Rhodanobacter denitrificans sp. nov., isolated from nitrate-rich zones of a
      contaminated aquifer.
AB  - Bacterial strains 2APBS1(T) and 116-2 were isolated from the subsurface of a
      nuclear legacy waste site where the sediments are co-contaminated with large
      amounts of acids, nitrate, metal radionuclides and other heavy metals. A
      combination of physiological and genetic assays indicated that these strains
      represent the first member of the genus Rhodanobacter shown to be capable of
      complete denitrification. Cells of strain 2APBS1(T) and 116-2 were Gram-negative,
      non-spore-forming rods, 3-5 um long and 0.25-0.5 um in diameter. The isolates
      were facultative anaerobes, and had temperature and pH optima for growth of 30 
      degrees C and pH 6.5; they were able to tolerate up to 2.0 % NaCl, although
      growth improved in its absence. Strains 2APBS1(T) and 116-2 contained fatty acid
      and quinone (ubiquinone-8; 100 %) profiles that are characteristic features of
      the genus Rhodanobacter. Although strains 2APBS1(T) and 116-2 shared high 16S
      rRNA gene sequence similarity with Rhodanobacter thiooxydans LCS2(T) (>99 %),
      levels of DNA-DNA relatedness between these strains were substantially below the
      70 % threshold used to designate novel species. Thus, based on genotypic,
      phylogenetic, chemotaxonomic and physiological differences, strains 2APBS1(T) and
      116-2 are considered to represent a single novel species of the genus
      Rhodanobacter, for which the name Rhodanobacter denitrificans sp. nov. is
      proposed. The type strain is 2APBS1(T) ( = DSM 23569(T) = JCM 17641(T)).

PMID- 22140176
TI  - Deferrisoma camini gen. nov., sp. nov., a moderately thermophilic, dissimilatory
      iron(III)-reducing bacterium from a deep-sea hydrothermal vent that forms a
      distinct phylogenetic branch in the Deltaproteobacteria.
AB  - A moderately thermophilic, anaerobic, dissimilatory iron(III)-reducing bacterium
      (strain S3R1(T)) was isolated from a deep-sea hydrothermal vent chimney located
      on the Eastern Lau Spreading Centre in the Pacific Ocean at a depth of about 2150
      m. Cells of strain S3R1(T) were ovals to short rods with a single polar
      flagellum, Gram-stain-negative, 0.5-0.6 um in diameter and 0.8-1.3 um long,
      growing singly or in pairs. The temperature range for growth was 36-62  degrees
      C, with an optimum at 50  degrees C. The pH range for growth was 5.5-7.5, with an
      optimum at pH 6.5. Growth of strain S3R1(T) was observed at NaCl concentrations
      ranging from 1.0 to 5.0 % (w/v), with an optimum at 2.0-2.5 % (w/v). The isolate
      used acetate, fumarate, malate, maleinate, succinate, propanol, palmitate,
      stearate, peptone and yeast extract as electron donors for growth and iron(III)
      reduction. All electron donors were oxidized completely to CO(2) and H(2)O.
      Iron(III) (in the form of ferrihydrite, ferric citrate or ferric
      nitrilotriacetate) and elemental sulfur (S(0)) were the electron acceptors that
      supported growth. The DNA G+C content was 64.4 mol%. Results of 16S rRNA gene
      sequence analysis showed that the novel bacterium was related to representatives
      of the orders Desulfuromonadales and Syntrophobacterales with 84-86 % sequence
      similarity and formed a distinct phylogenetic branch in the Deltaproteobacteria.
      On the basis of its physiological properties and results of phylogenetic
      analyses, it is proposed that the new isolate represents the sole species of a
      novel genus, Deferrisoma camini gen. nov., sp. nov. The type strain of
      Deferrisoma camini is S3R1(T) ( = DSM 24185(T)  = VKM B-2672(T)).

PMID- 22140177
TI  - Brenneria goodwinii sp. nov., associated with acute oak decline in the UK.
AB  - A group of nine Gram-negative staining, facultatively anaerobic bacterial strains
      isolated from native oak trees displaying symptoms of acute oak decline (AOD) in
      the UK were investigated using a polyphasic approach. 16S rRNA gene sequencing
      and phylogenetic analysis revealed that these isolates form a distinct lineage
      within the genus Brenneria, family Enterobacteriaceae, and are most closely
      related to Brenneria rubrifaciens (97.6 % sequence similarity to the type
      strain). Multilocus sequence analysis based on four housekeeping genes (gyrB,
      rpoB, infB and atpD) confirmed their position within the genus Brenneria, while
      DNA-DNA hybridization indicated that the isolates belong to a single taxon. The
      isolates can be differentiated phenotypically from their closest phylogenetic
      neighbours. The phylogenetic and phenotypic data demonstrate that these isolates
      from oak with symptoms of AOD represent a novel species in the genus Brenneria,
      for which the name Brenneria goodwinii sp. nov. (type strain FRB 141(T)  = R
      43656(T)  = BCC 845(T)  = LMG 26270(T)  = NCPPB 4484(T)) is proposed.

PMID- 22140178
TI  - Patient rights in Iran: a review article.
AB  - A significant development for conducting research on patient rights has been made
      in Iran over the past decade. This study is conducted in order to review and
      analyze the previous studies that have been made, so far, concerning patient
      rights in Iran. This is a comprehensive review study conducted by searching the
      Iranian databases, Scientific Information Database, Iranian Research Institute
      for Information Science and Technology, Iran Medex and Google using the Persian
      equivalent of keywords for 'awareness', 'attitude', and 'patient rights'. For
      pertinent Iranian papers published in English, scientific databases PubMed, and
      Google Scholar were searched using the keyword 'patient rights' and 'Iran'. A
      total of 41 Persian and five English articles were found for these keywords, only
      26 of which fulfilled the objective of our study. The increasing number of papers
      published indicates that from 1999 onwards, this subject has begun to draw the
      attention of Iranian researchers in a progressive fashion and Iranian papers in
      English have also been compiled and published in international sources.

PMID- 22140179
TI  - Ethical problems: In the face of sudden and unexpected death.
AB  - When people die suddenly and unexpectedly ethical issues often come to the fore.
      The aim of the study was to describe experiences of members of stroke teams in
      stroke units of ethical problems and how the teams manage the situation when
      caring for patients faced with sudden and unexpected death from stroke. Data were
      collected through four focus group interviews with 19 team members in stroke-unit
      teams, and analysed using interpretive content analysis. Three themes emerged
      from the analysis characterized by information, decisions about care and support
      for the next-of-kin in the changing and uncertain situation, with mutual trust as
      the core. Mutual trust, both within the stroke team and with next-of-kin was seen
      by the stroke-team members as a way of handling ethical problems by administering
      care with the patient's best interest at heart.

PMID- 22140180
TI  - Morality in the mundane: specific needs for ethics support in elderly care.
AB  - Ethics support is called for to improve the quality of care in elderly
      institutions. Various forms of ethics support are presented, but the needs for
      ethics support remain unknown. Using a mixed-methods design, this article
      systematically investigates the specific needs for ethics support in elderly
      care. The findings of two surveys, two focus groups and 17 interviews demonstrate
      that the availability of ethics support is limited. There is a need for ethics
      support, albeit not unconditionally. Advice-based forms of ethics support are
      less appropriate as they are removed from practice. Ethics support should be
      tailored to the often mundane and easily overlooked moral issues that arise in
      long-term care. Attention should also be given to the learning styles of nurses
      who favour experiential learning. Raising awareness and developing a climate of
      openness and dialogue are the most suitable ways to deal with the mundane moral
      issues in elderly care.

PMID- 22140181
TI  - Duties of the patient: a tentative model based on metasynthesis.
AB  - Patient's duties are a topical but little researched area in nursing ethics.
      However, patient's duties are closely connected to nursing practice in terms of
      autonomy, the best purpose of care and rethinking from the patient's perspective.
      This article is a metasynthesis (N = 11 original articles) of patient's duties,
      aimed to create a tentative model. In this article, a tentative model called
      'right-based duties of a patient' was constructed. With its aid, a coherent
      structure of patient's duties within different roles and objects of a patient can
      be defined. In addition, the ethical basis, prerequisites, outcomes and risks of
      patient's duties can be named. In conclusion, so-called right-based duties of a
      patient constitute the basic argument. Patient's duties are not unambiguous for
      all patients, and the global perspective to duties has been challenged. However,
      due to both conceptual and practical reasons, rethinking of patient's duties is
      needed.

PMID- 22140182
TI  - Ethical problems in practice as experienced by Malawian student nurses.
AB  - Student nurses are confronted by many ethical challenges in clinical practice.
      The aim of the study was to explore Malawian students' experiences of ethical
      problems during their clinical placement. A phenomenological hermeneutic design
      comprising interviews and qualitative content analysis was used. Ten students
      were interviewed. Three main themes emerged: 1) Conflict between patient rights
      and the guardians' presence in the hospital; 2) Conflict between violation of
      professional values and patient rights caused by unethical behaviour; and 3)
      Conflict between moral awareness and the ideal course of action. The students had
      difficulties ensuring patient rights and acting in accordance with western norms
      and values which are not always appropriate in the Malawian context. The students
      require role models who demonstrate professional attitudes towards patients'
      rights and values. There is a need to create pedagogical strategies in which a
      caring attitude and ethical reflection can be learned and cultivated in clinical
      practice.

PMID- 22140183
TI  - An analysis of common arguments against Advance Directives.
AB  - Advance Directives are under-utilized, both from the fact that few Americans have
      them and that health professionals don't always rely on Advance Directives
      provided by patients. Many health professionals have philosophical objections to
      their use. Using a fictitious case as background, five different objections to
      the use of Advance Directives will be discussed and arguments against those
      objections will be posed along with suggestions to improve Advance Directives.

PMID- 22140184
TI  - Balancing truth-telling in the preservation of hope: a relational ethics
      approach.
AB  - Truth-telling in healthcare practice can be regarded as a universal communicative
      virtue; however, there are different views on what consequence it has for giving
      or diminishing hope. The aim of this article is to explore the relationship
      between the concepts of truth-telling and hope from a relational ethics approach
      in the context of healthcare practice. Healthcare staff protect themselves and
      others to preserve hope in the care of seriously sick patients and in end-of-life
      care. This is done by balancing truth-telling guided by different conditions such
      as the cultural norms of patients, family and staff. Our main conclusion is that
      the balancing of truth-telling needs to be decided in a mutual understanding in
      the caring relationship, but hope must always be inspired. Instead of focusing on
      autonomy as the only guiding principle, we would like to propose that relational
      ethics can serve as a meaningful perspective in balancing truth-telling.

PMID- 22140185
TI  - A proto-code of ethics and conduct for European nurse directors.
AB  - The proto-code of ethics and conduct for European nurse directors was developed
      as a strategic and dynamic document for nurse managers in Europe. It invites
      critical dialogue, reflective thinking about different situations, and the
      development of specific codes of ethics and conduct by nursing associations in
      different countries. The term proto-code is used for this document so that
      specifically country-orientated or organization-based and practical codes can be
      developed from it to guide professionals in more particular or situation-explicit
      reflection and values. The proto-code of ethics and conduct for European nurse
      directors was designed and developed by the European Nurse Directors
      Association's (ENDA) advisory team. This article gives short explanations of the
      code' s preamble and two main parts: Nurse directors' ethical basis, and
      Principles of professional practice, which is divided into six specific points:
      competence, care, safety, staff, life-long learning and multi-sectorial working.

PMID- 22140186
TI  - Perceived ethical values by Iranian nurses.
AB  - Nursing, a scientific and practical discipline, faces continuing challenges of
      finding new direction in order to decipher its core values and develop current
      ethical codes for nursing practice. In 2009-10, 28 nurses were purposely selected
      and interviewed using a semi-structured format in focus groups and individually.
      Thematic Content Analysis helped explore the perception of Iranian nurses on
      ethical values in patient care. Seven major themes emerged: respect for dignity,
      professional integrity, professional commitment, developing human relationships,
      justice, honesty, and promoting individuals and the nursing profession. Iranian
      nurses revealed a unique and culture-based set of ethical values. This study
      found that Iranian nurses place a greater emphasis on preserving the dignity of
      those accompanying the patient and in showing regard for patients' religious
      beliefs in a gender appropriate environment.

PMID- 22140187
TI  - The challenge of integrating justice and care in neonatal nursing.
AB  - The aim of this study was to explore neonatal nurses' and mothers of preterm
      infants' experiences of daily challenges. Interviews took place asking for good,
      bad and challenging experiences. Data were analysed using qualitative content
      analysis and findings were clustered in two categories: good and challenging
      experiences, each containing three themes. The good experiences were: managing
      with success as a nurse, small things matter for mothers, and a good day anyhow
      for mothers and nurses. The challenging experiences were: mothering in public,
      being pulled between responsibilities, and adverse things stick under the nurses'
      skin. The study shows that small daily clinical matters become big issues and
      could lead to moral distress, and that nurses integrate ethics of justice and
      ethics of care while mothers are concerned about health and well-being of their
      specific infant only. The challenge for nursing to integrate fairness and
      sensitive care in family-oriented neonatal care is discussed.

PMID- 22140188
TI  - An explorative study of experiences of healthcare providers posing as simulated
      care receivers in a 'care-ethical' lab.
AB  - In recent approaches to ethics, the personal involvement of health care providers
      and their empathy are perceived as important elements of an overall ethical
      ability. Experiential working methods are used in ethics education to foster,
      inter alia, empathy. In 2008, the care-ethics lab 'sTimul' was founded in
      Flanders, Belgium, to provide training that focuses on improving care providers'
      ethical abilities through experiential working simulations. The curriculum of
      sTimul focuses on empathy sessions, aimed at care providers' empathic skills. The
      present study provides better insight into how experiential learning specifically
      targets the empathic abilities of care providers. Providing contrasting
      experiences that affect the care providers' self-reflection seems a crucial
      element in this study. Further research is needed to provide more insight into
      how empathy leads to long-term changes in behaviour.

PMID- 22140189
TI  - The experience of lying in dementia care: a qualitative study.
AB  - This analysis examines the practice of care providers in residential aged care
      lying to residents with dementia. Qualitative data were collected through
      multiple methods. Data here represents perceptions from registered and enrolled
      nurses, personal care assistants, and allied health professionals from five
      residential aged care facilities located in Queensland, Australia. Care providers
      in residential aged care facilities (RACFs) lie to residents with dementia. Lying
      is conceptualized as therapeutic whereby the care provider's intent is to
      eliminate harm and also control behaviour. Care providers of residents with
      dementia in RACFs need guidance around lying. An ethical framework cognisant of
      an ethical theory of good and ethical theory of right supplemented by a theory of
      virtue is proposed. A complimentary four stage communication strategy that
      promotes truth telling as a first option while also recommending the lie as a
      suitable strategy is also promoted.

PMID- 22140190
TI  - Variations in hospital worker perceptions of safety culture.
AB  - OBJECTIVE: To compare the attitudes toward and perceptions of institutional
      practices that can influence patient safety between all professional groups at a
      university medical center. DESIGN: A questionnaire measuring nine dimensions of
      organizational and safety culture was distributed to all hospital workers. Each
      item was rated on a 1 ('strongly disagree') to 5 ('strongly agree') scale.
      PARTICIPANTS: Professionals (2995), grouped as 'physicians' (16.6%), 'nurses'
      (40.3%), 'clinical workers' (e.g. psychologists; 21.7%), 'laboratory workers'
      (e.g. technicians; 11%) and 'non-medical workers' (e.g. managers; 10.4%). MAIN
      OUTCOME MEASURES: One-way analysis of variances (ANOVAs) carried out separately
      on each dimension with professional group as the independent variable of
      interest. RESULTS: Differences in ratings of organizational and safety culture
      were found across professional groups. Physicians and non-medical workers tended
      to rate the dimensions of organizational and safety culture more positively than
      did nurses, clinical workers and laboratory workers. For example, physicians gave
      more positive ratings of 'institutional commitment to safety' than did nurses,
      clinical workers and laboratory workers (mean = 3.71 vs. 3.62, 3.61 and 3.58,
      respectively, P < 0.01) and non-medical workers gave more positive ratings than
      did physicians, nurses, clinical workers and laboratory workers to 'perceptions
      towards the hospital' (mean = 3.69 vs. 3.39, 3.36, 3.49 and 3.47, respectively, P
      < 0.001). CONCLUSIONS: Interventions to promote safety culture should be tailored
      to the target group as attitudes and perceptions may differ among groups.

PMID- 22140191
TI  - An empirical test of short notice surveys in two accreditation programmes.
AB  - OBJECTIVE: To evaluate short notice surveys in accreditation programmes. DESIGN:
      Two trials using short notice surveys were conducted independently: a study of 20
      healthcare organizations with the Australian Council on Healthcare Standards
      (ACHS) and a study of 7 general practices with the Australian General Practice
      Accreditation Limited (AGPAL). Participating organizations volunteered. ACHS and
      AGPAL selected 17 and 13 surveyors, respectively, and provided training for them
      on short notice surveys. METHODS: Each agency's short notice surveys were an
      abbreviated version of their current advanced notification surveys. Short notice
      surveys assessed accreditation programme criteria or indicators that corresponded
      to the Australian Commission on Safety and Quality in Health Care's priority
      issues. Fifteen (out of 45) ACHS criteria and 48 (out of 174) AGPAL indicators
      that aligned to the Commission's criteria were evaluated. Participating
      organizations were given 2 days notice prior to the short notice surveys. Ratings
      from the short notice surveys were compared with those from the most recent
      advanced notification surveys, and statistical tests were performed to detect
      differences and potential confounding factors. Surveyors and organizational staff
      completed a post-survey feedback questionnaire which was analysed thematically
      and by inferential statistics. RESULTS: The short notice survey approach overall
      produced ratings congruent with the advanced notification survey for both
      accreditation programmes. However, for both programmes short notice surveys
      assessed that more organizations would not reach the accreditation threshold as
      compared with the previous survey. Organizations in both programmes were judged
      to have achieved less successful performance against clinical standards by the
      short notice survey than the advanced notification survey. There was support from
      surveyors and organizational staff for short notice survey to be adopted.
      However, there were mixed views about the impact of short notice surveys and
      whether they validated trial participants' continuous improvement efforts.
      CONCLUSIONS: The study demonstrated that short notice surveys are more critical
      in their assessment of clinical than administrative or corporate items. Short
      notice surveys, while broadly comparable with existing advanced notification
      survey practice, produced different accreditation outcomes for a significant
      proportion of the study organizations. The overall value and worth of short
      notice surveys remains to be proved.

PMID- 22140192
TI  - Regulating open disclosure: a German perspective.
AB  - The issue of open disclosure has received growing attention from policy-makers,
      legal experts and academic researchers, predominantly in a number of English
      speaking countries. While implementing open disclosure in practice is still an on
      going process, open disclosure now forms an integral part of health policy in
      various American states, the UK, Canada, Australia and New Zealand, with a number
      of measures having been put in place to encourage open disclosure and to mitigate
      some of the barriers to such open communication. In contrast, this issue has
      received little attention in non-English-speaking countries and there is
      currently no empirical data relating to actual practice or practitioners'
      attitudes and views in most countries in continental Europe. This article
      critically examines Germany's current approach to open disclosure. It finds that
      the issue plays no significant role in German health policy with very limited
      measures explicitly concerning such communication currently in place. While a
      number of aspects of the wider regulatory framework appear to be supportive,
      Germany is still in the early stages of a systematic approach and additional
      measures are required to further promote open disclosure within the self
      governing German healthcare system. This exploration provides an example of a non
      English-speaking country's approach to open disclosure and may be of particular
      interest to neighbouring German-speaking and civil law countries such as
      Switzerland and Austria.

PMID- 22140193
TI  - Process analysis to reduce MRI access time at a German University Hospital.
AB  - QUALITY PROBLEM OR ISSUE: Long access times for magnetic resonance imaging (MRI)
      can negatively impact the quality of care provided to patients. We investigated
      improving access by reducing MRI processing time. INITIAL ASSESSMENT: Data were
      collected for scans (n= 360) performed over 3 weeks (April-May 2008) at the
      University Hospital of Mannheim, Germany. Average access time, excluding
      emergencies, was 44 (+/-44) days for outpatients and 3 (+/-5) days for
      inpatients. Factors influencing total MRI processing time were identified using
      multivariate linear regression. In addition to region scanned, the total MRI
      processing time was significantly related to performing multiple scans (beta =
      33.57, P< 0.01), using oral contrast media (beta = 13.58, P< 0.01), placing an
      intravenous (IV) catheter (beta = 5.00, P= 0.04) and scanning patients <=8 years
      old (beta = 0.41, P= 0.03). Contrary to prior perceptions, emergency cases (5.6%)
      and late arrivals (12.8% >5 min late) were less than expected. CHOICE OF
      SOLUTION: Increasing scheduling flexibility to address non-modifiable process
      variation and completing preparatory activities outside the scanner room were
      identified as process improvement targets. IMPLEMENTATION: Scheduling was adapted
      to utilize three expected total MRI processing times and IV placement was moved
      outside the scanner room. EVALUATION: Planned hardware and software upgrades were
      completed concurrent to the process improvements. As a result, it was not
      possible to accurately measure the effect of implementing the scheduling and
      preparatory activity changes. LESSONS LEARNED: Clinical study team members' prior
      perceptions of workflow obstacles did not match the study findings. Utilizing
      insiders and outsiders during process analysis may limit bias in identification
      of process improvement opportunities.

PMID- 22140194
TI  - Studies pertaining to the ACOVE quality criteria: a systematic review.
AB  - PURPOSE: To identify and uniformly describe studies employing the Assessing Care
      Of Vulnerable Elders (ACOVE) quality indicators within a comprehensive thematic
      model that reflects how the indicators were used. DATA SOURCES: A systematic
      search of MEDLINE, EMBASE and CINAHL was conducted. STUDY SELECTION: English
      language studies meeting our criteria published prior to January 2010. Data
      extraction Included studies were analyzed and described by two independent
      researchers. RESULTS OF DATA SYNTHESIS: A total of 41 articles met our selection
      criteria. Studies were classified into the themes 'Application of indicators' (32
      studies) and ' ANALYSIS: and development of indicators' (13 studies).
      'Application' studies included assessing quality of care, influencing behavior of
      health professionals and examining the association of quality of care with other
      factors. 'Analysis and development' included studies developing new indicator
      sets, and those adapting and validating the original quality indicators to new
      settings. CONCLUSIONS: The indicators were used in a wide range of applications
      with two main foci: the assessment of quality of care for elderly patients, and
      investigating the feasibility of similar indicators and their adaptation to new
      settings. Very few of the studies published to date have addressed the goal of
      care improvement. We foresee an important role for application of indicators that
      proactively help health-care professionals to deliver the right care at the right
      time, for example by resorting to decision support systems.

PMID- 22140195
TI  - Contralesional motor cortex activation depends on ipsilesional corticospinal
      tract integrity in well-recovered subcortical stroke patients.
AB  - BACKGROUND: The relationship between structural and functional integrity of
      descending motor pathways can predict the potential for motor recovery after
      stroke. The authors examine the relationship between brain imaging biomarkers
      within contralesional and ipsilesional hemispheres and hand function in well
      recovered patients after subcortical stroke at the level of the internal capsule.
      OBJECTIVE:  MEASURES: of functional activation and integrity of the ipsilesional
      corticospinal tract might predict paretic hand function. METHODS: A total of 14
      patients in the chronic stable phase of motor recovery after subcortical stroke
      and 24 healthy age-matched individuals participated in the study. Functional MRI
      was used to examine BOLD contrast during passive wrist flexion-extension and
      paced or maximum-velocity active fist clenching. Functional integrity of the
      corticospinal pathway was assessed by transcranial magnetic stimulation to obtain
      motor-evoked potentials (MEPs) in the first dorsal interosseus muscle of the
      paretic and nonparetic hands. Fractional anisotropy and the proportion of traces
      between hemispheres in the posterior limb of both internal capsules were
      quantified using diffusion-weighted MRI. RESULTS: Patients with smaller MEPs had
      a weaker paretic hand and more primary motor cortex activation in their affected
      hemisphere. Asymmetry between white matter tracts of either hemisphere was
      associated with reduced precision grip strength and increased BOLD activation
      within the contralesional dorsal premotor cortex for demanding hand tasks.
      CONCLUSION: There may be beneficial reorganization in contralesional secondary
      motor areas with increasing damage to the corticospinal tract after subcortical
      stroke. Associations between clinical, functional, and structural integrity
      measures in chronic stroke may lead to a better understanding of motor recovery
      processes.

PMID- 22140196
TI  - Quadriceps muscle weakness, activation deficits, and fatigue with Parkinson
      disease.
AB  - BACKGROUND: People with Parkinson disease (PD) typically have complaints of
      weakness. The mechanisms underlying this deficit have not been well established,
      although many factors may contribute. OBJECTIVE: This investigation aimed to
      characterize quadriceps muscle weakness and activation failure in people with PD
      and explore whether these deficits were related to disease severity. The authors
      further sought to examine quadriceps muscle fatigability. METHODS: This was a
      cross-sectional comparison of 17 people with mild-severe PD and 17 healthy adults
      matched by age, sex, and body mass index (BMI). The Unified Parkinson's Disease
      Rating Scale motor score (UPDRS motor) ranged from 9.5 to 61.0. Participants were
      divided into those with low-PD motor signs (UPDRS motor < 31.7) and high-PD motor
      signs (UPDRS motor >= 31.7). Measures of quadriceps performance included
      isometric torque, central activation using doublet interpolation, and an
      isokinetic fatigue test. RESULTS: Participants with high-PD motor signs had
      significantly more quadriceps weakness and central activation deficits than those
      with low-PD motor signs or healthy controls. Strength and activation deficits
      correlated strongly with UPDRS motor score. Quadriceps muscle fatigue was present
      in healthy controls and in those with low-PD motor signs but not in those with
      high-PD motor signs. CONCLUSIONS: These findings provide additional evidence for
      lower-extremity strength loss with PD; central activation deficits may account
      for some of the strength deficits, especially with increased PD motor signs.
      Also, muscle fatigue did not occur in individuals with a greater degree of PD
      motor signs, most likely because of insufficient central activation to allow for
      muscle overload to induce metabolic fatigue.

PMID- 22140197
TI  - Robotic-assisted step training (lokomat) not superior to equal intensity of over
      ground rehabilitation in patients with multiple sclerosis.
AB  - BACKGROUND: Robot-assisted gait training (RAGT) has been suggested as an
      intervention to improve walking capacity in patients with multiple sclerosis
      (MS). OBJECTIVE: This study aimed to evaluate whether RAGT (Lokomat) is superior
      to over-ground walking training in terms of quality of life, activity level, and
      gait. METHODS: A total of 67 patients with MS with the Expanded Disability Status
      Scale (EDSS) 3.0 to 6.5 were randomized to walking or RAGT, in addition to
      multimodal rehabilitation. Primary outcomes were walking speed, activity level
      (estimated metabolic equivalent, metabolic equivalents [METs], using an
      accelerometer), and quality of life (Well-Being Visual Analogue Scale (VAS) and
      EQ-5D European VAS. RESULTS: In all, 49 patients finished the interventions. Mean
      age was 56 years (range 36-74 years), mean EDSS was 5.8 (3.0-6.5), and the
      preferred walking speed at baseline was 0.56 m/s (0.06-1.43 m/s). Before
      rehabilitation, participants spent on average 68 min/d at an MET >= 3. The
      walking group improved gait speed nonsignificantly more than the RAGT; the upper
      bound of the confidence interval (CI) did not exclude a clinically relevant
      benefit (defined as a difference of 0.05 m/s) in favor of the walking group; the
      lower bound of the CI did exclude a clinically important benefit in favor of the
      Lokomat. Quality of life improved in both groups, with a nonsignificant between
      group difference in favor of the walking group. Both groups had reduced their
      activity by 8 weeks after the rehabilitation. CONCLUSION: It is unlikely that
      RAGT is better than over-ground walking training in patients with an EDSS between
      3.0 and 6.5.

PMID- 22140199
TI  - A randomized controlled trial comparing 2 interventions for visual field loss
      with standard occupational therapy during inpatient stroke rehabilitation.
AB  - BACKGROUND AND PURPOSE: Compensatory and restorative treatments have been
      developed to improve visual field defects after stroke. However, no controlled
      trials have compared these interventions with standard occupational therapy (OT).
      METHODS: A total of 45 stroke participants with visual field defect admitted for
      inpatient rehabilitation were randomized to restorative computerized training
      (RT) using computer-based stimulation of border areas of their visual field
      defects or to a computer-based compensatory therapy (CT) teaching a visual search
      strategy. OT, in which different compensation strategies were used to train for
      activities of daily living, served as standard treatment for the active control
      group. Each treatment group received 15 single sessions of 30 minutes distributed
      over 3 weeks. The primary outcome measures were visual field expansion for RT,
      visual search performance for CT, and reading performance for both treatments.
      Visual conjunction search, alertness, and the Barthel Index were secondary
      outcomes. RESULTS: Compared with OT, CT resulted in a better visual search
      performance, and RT did not result in a larger expansion of the visual field.
      Intragroup pre-post comparisons demonstrated that CT improved all defined outcome
      parameters and RT several, whereas OT only improved one. CONCLUSIONS: CT improved
      functional deficits after visual field loss compared with standard OT and may be
      the intervention of choice during inpatient rehabilitation. A larger trial that
      includes lesion location in the analysis is recommended.

PMID- 22140198
TI  - Need for speed: better movement quality during faster task performance after
      stroke.
AB  - BACKGROUND: . Although slow and insufficient muscle activation is a hallmark of
      hemiparesis poststroke, movement speed is rarely emphasized during upper
      extremity rehabilitation. Moving faster may increase the intensity of task
      specific training, but positive and/or negative effects on paretic-limb movement
      quality are unknown. OBJECTIVE: . To determine whether moving quickly instead of
      at a preferred speed either enhances or impairs paretic-limb task performance
      after stroke. METHODS: . A total of 16 people with poststroke hemiparesis and 11
      healthy controls performed reach-grasp-lift movements at their preferred speed
      and as fast as possible, using palmar and 3-finger grip types. The authors
      measured durations of the reach and grasp phases, straightness of the reach path,
      thumb-index finger separation (aperture), efficiency of finger movement, and grip
      force. RESULTS: . Reach and grasp phase durations decreased in the fast condition
      in both groups, showing that participants were able to move more quickly when
      asked. When moving fast, the hemiparetic group had reach durations equal to those
      of healthy controls moving at their preferred speed. Movement quality also
      improved. Reach paths were straighter, and peak apertures were greater in both
      groups in the fast condition. The group with hemiparesis also showed improved
      efficiency of finger movement. Differences in peak grip force across speed
      conditions did not reach significance. CONCLUSIONS: . People with hemiparesis who
      can perform reach-grasp-lift movements with a 3-finger grip can move faster than
      they choose to, and when they do, movement quality improves. Simple instructions
      to move faster could be a cost-free and effective means of increasing
      rehabilitation intensity after stroke.

PMID- 22140200
TI  - Cerebellar ataxia rehabilitation trial in degenerative cerebellar diseases.
AB  - OBJECTIVE: To investigate short- and long-term effects of intensive
      rehabilitation on ataxia, gait, and activities of daily living (ADLs) in patients
      with degenerative cerebellar disease. METHODS: A total of 42 patients with pure
      cerebellar degeneration were randomly assigned to the immediate group or the
      delayed-entry control group. The immediate group received 2 hours of inpatient
      physical and occupational therapy, focusing on coordination, balance, and ADLs,
      on weekdays and 1 hour on weekends for 4 weeks. The control group received the
      same intervention after a 4-week delay. Short-term outcome was compared between
      the immediate and control groups. Long-term evaluation was done in both groups at
      4, 12, and 24 weeks after the intervention. Outcome measures included the
      assessment and rating of ataxia, Functional Independence Measure, gait speed,
      cadence, functional ambulation category, and number of falls. RESULTS: The
      immediate group showed significantly greater functional gains in ataxia, gait
      speed, and ADLs than the control group. Improvement of truncal ataxia was more
      prominent than limb ataxia. The gains in ataxia and gait were sustained at 12
      weeks and 24 weeks, respectively. At least 1 measure was better than at baseline
      at 24 weeks in 22 patients. CONCLUSIONS: Short-term benefit of intensive
      rehabilitation was evident in patients with degenerative cerebellar diseases.
      Although functional status tended to decline to the baseline level within 24
      weeks, gains were maintained in more than half of the participants.

PMID- 22140202
TI  - How hospital leaders implemented a safe surgery protocol in Australian hospitals.
AB  - OBJECTIVE: To analyse the strategies used by hospital leaders to improve
      compliance with the 'ensuring correct patient, correct site and correct procedure
      protocol'. While following such a protocol saves lives according to an
      international study of the World Health Organization safe surgery checklist,
      promoting compliance in hospitals has proved to be a regulatory challenge.
      DESIGN:  SETTING AND PARTICIPANTS: Using a qualitative research design and
      'responsive regulation' theory, this study explored implementation strategies
      used by hospital leaders in 20 Australian public hospitals. Semi-structured
      interviews were conducted with 72 informants to analyse how front-line leaders
      improved compliance with the safe surgery protocol in their hospitals.
      INTERVENTIONS: Implementation analysis of the safe surgery protocol. MAIN OUTCOME
      MEASURES: The use of implementation strategies located on a 'responsive
      regulation' pyramid. RESULTS: Informants identified many strategies used to
      improve protocol compliance typically beginning with persuasion. Supportive
      strategies were located on a regulatory pyramid beginning with softer
      interventions: persuade, enlist leaders, train, remind, relax protocol
      requirements, redesign hospital systems and reward compliance. In response to low
      and slow compliance, many hospital leaders switched to a pyramid of escalating
      sanctions: direct, delegate, monitor, publicly report, reprimand and penalize.
      CONCLUSIONS: A multiplex problem requires graduated and multiplex regulation.
      Hospital leaders proved to be responsive regulators in applying both multiple
      supports and sanctions that improved compliance over 3 years. These experiences
      with protocol implementation illustrate the multifaceted challenge of health
      sector regulation and offer lessons for embedding future patient safety
      solutions.

PMID- 22140201
TI  - Useful models of asthma need to properly phenotype airway narrowing.

PMID- 22140203
TI  - Evaluation of the Pharmacy Safety Climate Questionnaire in European community
      pharmacies.
AB  - OBJECTIVE: To evaluate the internal reliability, factor structure and construct
      validity of the Pharmacy Safety Climate Questionnaire (PSCQ) when applied to a
      pan-European sample of community pharmacies. DESIGN: A cross-sectional survey
      design was used. SETTING: Community pharmacies in Denmark, Germany, the
      Netherlands, Portugal and Great Britain. PARTICIPANTS: A total of 4105 members of
      the community pharmacy workforce, all drawn from one of the five participating
      countries. MAIN OUTCOME MEASURES: Each participant completed a copy of the
      Pharmacy Safety Climate Questionnaire in his or her respective language and rated
      the perceived safety of the pharmacy in which he or she worked. RESULTS:
      Exploratory and confirmatory factor analyses of the data identified four factors
      that accounted for item responses, with 24 of the original 34 items loading onto
      them. They were labelled organizational learning, blame culture, working
      conditions and safety focus. These factors were found to have an acceptable level
      of reliability (with Cronbach's alpha values ranging from 0.70 to 0.92) and to
      predict the rating of pharmacy safety. CONCLUSIONS: This study provided
      information on the PSCQ's psychometric properties when used in community
      pharmacies in different European countries. A modified version of the original
      PSCQ (known as PSCQ-4) is presented, and further work is proposed to demonstrate
      its application to safety improvements in pharmacies.

PMID- 22140204
TI  - Early intervention: distraction osteogenesis of the mandible for severe airway
      obstruction.
AB  - OBJECTIVE: To determine benefits of early intervention in neonates with
      symptomatic micrognathia who underwent bilateral mandibular distraction
      osteogenesis within the first 90 days of life as relates to growth, need for
      supportive care, and further invasive procedures. STUDY DESIGN: Case series with
      chart review. SETTING: Tertiary care, academic children's hospital. SUBJECTS AND
      METHODS: Review of neonates with symptomatic micrognathia who underwent bilateral
      mandibular distraction osteogenesis in the past 5 years. Inclusion criteria
      included mandibular distraction osteogenesis performed within the first 90 days
      of life. Outcome measures included hospital course, growth curves, supportive
      home care needs, and airway at cleft repair. RESULTS: Twenty-four patients met
      inclusion criteria. The mean age at distraction was 30 days, and the average
      discharge was postoperative day 14. One patient required home oxygen, 50% were
      able to feed exclusively by oral diet, and no patients required tracheotomy. In
      addition, airway results were substantial, with 90% of patients showing objective
      improvement in airway grade from time of mandibular distraction to time of cleft
      repair. CONCLUSION: We present our initial outcomes on mandibular distraction
      osteogenesis in neonates with symptomatic micrognathia. Early intervention allows
      discharge to home with minimal supportive care needs by avoiding tracheostomy and
      facilitating transition to oral feeds. The airway improvement is significant and
      is sustained and allows for easier intubation at time of cleft repair.

PMID- 22140205
TI  - Electrocochleography in round window Vibrant Soundbridge implantation.
AB  - OBJECTIVE: To determine the role of intraoperative electrocochleography to
      optimize the fitting of the floating mass transducer of the Vibrant Soundbridge
      on the round window membrane in patients with conductive and mixed hearing loss.
      STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center,
      Otolaryngology Department, University of Verona, Verona, Italy. SUBJECTS AND
      METHODS: Twenty-six adult patients suffering from chronic otitis media with
      moderate to severe conductive and mixed hearing loss, all with previous
      unsuccessful functional surgery, underwent round window vibroplasty. Thirteen
      subjects had intraoperative compound cochlear action potentials measured to
      assess vibroplasty coupling during and after surgery. In these patients, surgery
      was modified according to electrocochleographic feedback. The other 13 had
      vibroplasty without electrocochleography monitoring. RESULTS: The average
      preoperative air conduction and bone conduction thresholds (0.5-4 kHz) were not
      statistically significantly different between the 2 cohorts (P > .05). Compound
      action potential recordings indicated specific surgical modalities to optimize
      coupling of the floating mass transducer with the round window membrane. The
      average postoperative Vibrant Soundbridge-aided air conduction threshold
      improvements (0.5-4 kHz) were 54.6 +/- 8.9 and 41.7 +/- 11.1 dB HL, respectively,
      in the monitored and unmonitored cohorts (P = .0032). CONCLUSION: Improved round
      window vibroplasty outcomes are observed when the surgeon is promptly informed of
      the compound action potential changes induced by the floating mass transducer
      round window membrane vibroplasty and alters surgery accordingly. The key point
      for optimal coupling is a floating mass transducer in full contact with the round
      window membrane, free to vibrate without any contact with the surrounding bony
      structures and mobile footplate.

PMID- 22140206
TI  - Cochlear implantation in children with anomalous cochleovestibular anatomy: a
      systematic review.
AB  - OBJECTIVE: To determine the influence of inner ear dysplasia on both surgical and
      audiologic outcomes following pediatric cochlear implant (CI) surgery. DATA
      SOURCES: MEDLINE (1982-2009) and data from Massachusetts Eye and Ear Infirmary.
      REVIEW METHODS: A systematic review of the literature was performed. Variables
      assessed included age at implantation, duration of CI use, radiologic and
      operative findings, and speech perception outcome data. RESULTS: The initial
      search yielded 1326 articles. Including data from our own study, twenty-two
      fulfilled criteria for inclusion, representing 311 patients. Data for bilateral
      implants were recorded only for the first implant. Data on simultaneous bilateral
      implants were not recorded. The most common anomaly seen was large vestibular
      aqueduct (89/311 or 29%). When comparing patients with mild-moderate or severe
      dysplasia, rates of cerebrospinal fluid gusher were 31% versus 35% (odds ratio
      [OR] = 0.50), anomalous facial nerve anatomy was seen in 11% versus 51% (OR =
      0.15), and postoperative speech perception abilities were found in 84% versus 54%
      (OR = 1.93), respectively. A large heterogeneity was found among studies
      regarding all outcome measures. CONCLUSION: Although we found that severe inner
      ear dysplasia was associated with increased surgical difficulty and lower speech
      perception, the lack of uniformity in published clinical data limited the
      strength of these results. Standardization of surgical and radiologic reporting
      as well as more consistent speech perception testing is needed to better
      determine the association between anomalous cochleovestibular anatomy and
      clinical outcomes.

PMID- 22140207
TI  - Automated discovery of drug treatment patterns for endocrine therapy of breast
      cancer within an electronic medical record.
AB  - OBJECTIVE: To develop an algorithm for the discovery of drug treatment patterns
      for endocrine breast cancer therapy within an electronic medical record and to
      test the hypothesis that information extracted using it is comparable to the
      information found by traditional methods. MATERIALS: The electronic medical
      charts of 1507 patients diagnosed with histologically confirmed primary invasive
      breast cancer. METHODS: The automatic drug treatment classification tool
      consisted of components for: (1) extraction of drug treatment-relevant
      information from clinical narratives using natural language processing (clinical
      Text Analysis and Knowledge Extraction System); (2) extraction of drug treatment
      data from an electronic prescribing system; (3) merging information to create a
      patient treatment timeline; and (4) final classification logic. RESULTS:
      Agreement between results from the algorithm and from a nurse abstractor is
      measured for categories: (0) no tamoxifen or aromatase inhibitor (AI) treatment;
      (1) tamoxifen only; (2) AI only; (3) tamoxifen before AI; (4) AI before
      tamoxifen; (5) multiple AIs and tamoxifen cycles in no specific order; and (6) no
      specific treatment dates. Specificity (all categories): 96.14%-100%; sensitivity
      (categories (0)-(4)): 90.27%-99.83%; sensitivity (categories (5)-(6)): 0-23.53%;
      positive predictive values: 80%-97.38%; negative predictive values: 96.91%
      99.93%. DISCUSSION: Our approach illustrates a secondary use of the electronic
      medical record. The main challenge is event temporality. CONCLUSION: We present
      an algorithm for automated treatment classification within an electronic medical
      record to combine information extracted through natural language processing with
      that extracted from structured databases. The algorithm has high specificity for
      all categories, high sensitivity for five categories, and low sensitivity for two
      categories.

PMID- 22140209
TI  - Ambulatory prescribing errors among community-based providers in two states.
AB  - OBJECTIVE: Little is known about the frequency and types of prescribing errors in
      the ambulatory setting among community-based, primary care providers. Therefore,
      the rates and types of prescribing errors were assessed among community-based,
      primary care providers in two states. MATERIAL AND METHODS: A non-randomized
      cross-sectional study was conducted of 48 providers in New York and 30 providers
      in Massachusetts, all of whom used paper prescriptions, from September 2005 to
      November 2006. Using standardized methodology, prescriptions and medical records
      were reviewed to identify errors. RESULTS: 9385 prescriptions were analyzed from
      5955 patients. The overall prescribing error rate, excluding illegibility errors,
      was 36.7 per 100 prescriptions (95% CI 30.7 to 44.0) and did not vary
      significantly between providers from each state (p=0.39). One or more non
      illegibility errors were found in 28% of prescriptions. Rates of illegibility
      errors were very high (175.0 per 100 prescriptions, 95% CI 169.1 to 181.3).
      Inappropriate abbreviation and direction errors also occurred frequently (13.4
      and 4.2 errors per 100 prescriptions, respectively). Reviewers determined that
      the vast majority of errors could have been eliminated through the use of e
      prescribing with clinical decision support. DISCUSSION: Prescribing errors appear
      to occur at very high rates among community-based primary care providers,
      especially when compared with studies of academic-affiliated providers that have
      found nearly threefold lower error rates. Illegibility errors are particularly
      problematical. CONCLUSIONS: Further characterizing prescribing errors of
      community-based providers may inform strategies to improve ambulatory medication
      safety, especially e-prescribing. TRIAL REGISTRATION NUMBER:
      http://www.clinicaltrials.gov, NCT00225576.

PMID- 22140208
TI  - Triaging patients at risk of influenza using a patient portal.
AB  - Vanderbilt University has a widely adopted patient portal, MyHealthAtVanderbilt,
      which provides an infrastructure to deliver information that can empower patient
      decision making and enhance personalized healthcare. An interdisciplinary team
      has developed Flu Tool, a decision-support application targeted to patients with
      influenza-like illness and designed to be integrated into a patient portal. Flu
      Tool enables patients to make informed decisions about the level of care they
      require and guides them to seek timely treatment as appropriate. A pilot version
      of Flu Tool was deployed for a 9-week period during the 2010-2011 influenza
      season. During this time, Flu Tool was accessed 4040 times, and 1017 individual
      patients seen in the institution were diagnosed as having influenza. This early
      experience with Flu Tool suggests that healthcare consumers are willing to use
      patient-targeted decision support. The design, implementation, and lessons
      learned from the pilot release of Flu Tool are described as guidance for
      institutions implementing decision support through a patient portal
      infrastructure.

PMID- 22140210
TI  - Adoption of a wiki within a large internal medicine residency program: a 3-year
      experience.
AB  - OBJECTIVE: To describe the creation and evaluate the use of a wiki by medical
      residents, and to determine if a wiki would be a useful tool for improving the
      experience, efficiency, and education of housestaff. MATERIALS AND METHODS: In
      2008, a team of medical residents built a wiki containing institutional knowledge
      and reference information using Microsoft SharePoint. We tracked visit data for 3
      years, and performed an audit of page views and updates in the second year. We
      evaluated the attitudes of medical residents toward the wiki using a survey.
      RESULTS: Users accessed the wiki 23,218, 35,094, and 40,545 times in each of
      three successive academic years from 2008 to 2011. In the year two audit, 85
      users made a total of 1082 updates to 176 pages and of these, 91 were new page
      creations by 17 users. Forty-eight percent of residents edited a page. All
      housestaff felt the wiki improved their ability to complete tasks, and 90%, 89%,
      and 57% reported that the wiki improved their experience, efficiency, and
      education, respectively, when surveyed in academic year 2009-2010. DISCUSSION: A
      wiki is a useful and popular tool for organizing administrative and educational
      content for residents. Housestaff felt strongly that the wiki improved their
      workflow, but a smaller educational impact was observed. Nearly half of the
      housestaff edited the wiki, suggesting broad buy-in among the residents.
      CONCLUSION: A wiki is a feasible and useful tool for improving information
      retrieval for house officers.

PMID- 22140211
TI  - Proposed pathogenesis of Paget-Schroetter disease: impingement of the subclavian
      vein by a congenitally malformed bony tubercle on the first rib.
AB  - AIM: To study and compare the anatomical and clinical pathology of first ribs in
      patients with Paget-Schroetter Disease (PSD) with first ribs in patients without
      the disease. METHODS: In a case-control study, normal human cadaver first ribs
      were compared with first ribs from patients with PSD. Ribs, intraoperative videos
      of transthoracic en bloc surgical resection of the first rib, and preoperative
      and postoperative dynamic upper extremity venograms were reviewed. RESULTS:
      Fifteen first ribs were from patients with PSD and seven normal first ribs were
      from human cadavers. In all patients (100%) with PSD there was a bony tubercle
      that corresponded to the area of the subclavian vein groove in the normal ribs.
      In all controls (100%), there was a normal subclavian groove without the presence
      of a tubercle. On preoperative venograms in patients with PSD, the tubercle
      accounted for an extrinsic protuberance that compressed the subclavian vein
      (100%). Intraoperatively, the abnormal bony tubercle accounted for the extrinsic
      compression of the subclavian vein in all (100%) patients with PSD. Venograms of
      the upper extremity obtained after first rib resection showed the disappearance
      of the extrinsic compression on the subclavian vein (100%) and a patent
      subclavian vein with elevation of the arm in all patients. CONCLUSIONS: A bony
      tubercle at the site of the subclavian vein groove in patients with PSD causes
      extrinsic compression of the subclavian vein at rest.

PMID- 22140212
TI  - BAP1tism of a tumor suppressor.
AB  - Driving cancer cells into a more differentiated state is a rational therapeutic
      approach. Primary uveal melanoma cells with a propensity to metastasize have less
      differentiated features than their less aggressive counterparts. Treatment of
      uveal melanoma cells with histone deacetylase inhibitors induces a more
      differentiated phenotype with resultant lower growth capacity.

PMID- 22140213
TI  - Impact of the introduction of guidelines on vitamin B12 testing.

PMID- 22140214
TI  - Breaking the bottleneck in the protein biomarker pipeline.

PMID- 22140215
TI  - RAC: Repository of Antibiotic resistance Cassettes.
AB  - Antibiotic resistance in bacteria is often due to acquisition of resistance genes
      associated with different mobile genetic elements. In Gram-negative bacteria,
      many resistance genes are found as part of small mobile genetic elements called
      gene cassettes, generally found integrated into larger elements called integrons.
      Integrons carrying antibiotic resistance gene cassettes are often associated with
      mobile elements and here are designated 'mobile resistance integrons' (MRIs).
      More than one cassette can be inserted in the same integron to create arrays that
      contribute to the spread of multi-resistance. In many sequences in databases such
      as GenBank, only the genes within cassettes, rather than whole cassettes, are
      annotated and the same gene/cassette may be given different names in different
      entries, hampering analysis. We have developed the Repository of Antibiotic
      resistance Cassettes (RAC) website to provide an archive of gene cassettes that
      includes alternative gene names from multiple nomenclature systems and allows the
      community to contribute new cassettes. RAC also offers an additional function
      that allows users to submit sequences containing cassettes or arrays for
      annotation using the automatic annotation system Attacca. Attacca recognizes
      features (gene cassettes, integron regions) and identifies cassette arrays as
      patterns of features and can also distinguish minor cassette variants that may
      encode different resistance phenotypes (aacA4 cassettes and bla cassettes
      encoding beta-lactamases). Gaps in annotations are manually reviewed and those
      found to correspond to novel cassettes are assigned unique names. While there are
      other websites dedicated to integrons or antibiotic resistance genes, none
      includes a complete list of antibiotic resistance gene cassettes in MRI or offers
      consistent annotation and appropriate naming of all of these cassettes in
      submitted sequences. RAC thus provides a unique resource for researchers, which
      should reduce confusion and improve the quality of annotations of gene cassettes
      in integrons associated with antibiotic resistance. DATABASE URL:
      http://www2.chi.unsw.edu.au/rac.

PMID- 22140216
TI  - Is it abuse? Deaf female undergraduates' labeling of partner violence.
AB  - The current study investigated the labeling of abuse experiences in a sample of
      97 Deaf female undergraduate students, exploring the following questions: What is
      the prevalence of violent behaviors experienced by Deaf female undergraduates in
      their past-year relationships, what proportion of these relationships are
      identified as "abuse," and what scripts and strategies do Deaf female
      undergraduates utilize to label their experiences of partner violence? Results
      indicated that over half of the sample chose not to label past-year experiences
      of psychological aggression, physical assault, and sexual coercion as abuse, even
      when these experiences included severe violence. Implications for the Deaf
      education system will be discussed.

PMID- 22140217
TI  - Development and characterization of microsatellites in Torreya jackii (Taxaceae),
      an endangered species in China.
AB  - PREMISE OF THE STUDY: Polymorphic microsatellite loci were developed in Torreya
      jackii, an endangered species in China, to provide markers for further studies on
      the genetic diversity of this species. METHODS AND RESULTS: Eight polymorphic
      loci and one monomorphic locus were developed and characterized in four T. jackii
      populations (Xianju, Songyang, Pujiang, and Tonglu) from Zhejiang Province,
      China. The number of alleles per locus ranged from one to eight across 80 T.
      jackii individuals. At the eight polymorphic loci, the observed heterozygosity
      ranged from 0.150 to 1.000 and the expected heterozygosity ranged from 0.185 to
      0.796. CONCLUSIONS: The microsatellite loci developed and characterized in this
      study will facilitate future analyses of the genetic diversity of T. jackii. Such
      information will aid in designing strategies to conserve this currently
      endangered species.

PMID- 22140218
TI  - Microsatellite primers for the narrowly endemic shrub Eriogonum giganteum
      (Polygonaceae).
AB  - PREMISE OF THE STUDY: Microsatellite primers were designed for Eriogonum
      giganteum var. formosum, an endemic shrub of San Clemente Island, to investigate
      population structure, genetic diversity, and demographic history. METHODS AND
      RESULTS: Twelve polymorphic microsatellite loci were isolated from the California
      Channel Island endemic Eriogonum and were screened for variability. The primers
      amplified one to eight alleles in the target taxon. Many primers also amplified
      in conspecific and congeneric (E. arborescens, E. fasciculatum, E. grande, E.
      latifolium, and E. parvifolium) taxa and in the closely related Chorizanthe
      valida. The total number of alleles per locus for all taxa screened ranged from
      three to 24. CONCLUSIONS: These primers will be useful for conservation genetic
      and evolutionary studies within the California Channel Island endemic Eriogonum.

PMID- 22140219
TI  - Review: some universal family-based prevention programmes provide small
      reductions in alcohol use in youths in the short and long term.

PMID- 22140220
TI  - Review: supportive interventions may improve short-term psychological distress in
      informal caregivers of patients at the end of life.

PMID- 22140221
TI  - Review: some evidence of impaired neurocognitive performance in children and
      adolescents with bipolar disorder.

PMID- 22140223
TI  - A right coronary artery fistula communicating with a large right atrial
      pseudoaneurysm.

PMID- 22140224
TI  - A&E quality indicators.

PMID- 22140225
TI  - Designing out violence and aggression.

PMID- 22140226
TI  - Protein kinase A contributes to the negative control of Snf1 protein kinase in
      Saccharomyces cerevisiae.
AB  - Snf1 protein kinase regulates responses to glucose limitation and other stresses.
      Snf1 activation requires phosphorylation of its T-loop threonine by partially
      redundant upstream kinases (Sak1, Tos3, and Elm1). Under favorable conditions,
      Snf1 is turned off by Reg1-Glc7 protein phosphatase. The reg1 mutation causes
      increased Snf1 activation and slow growth. To identify new components of the Snf1
      pathway, we searched for mutations that, like snf1, suppress reg1 for the slow
      growth phenotype. In addition to mutations in genes encoding known pathway
      components (SNF1, SNF4, and SAK1), we recovered "fast" mutations, designated fst1
      and fst2. Unusual morphology of the mutants in the Sigma1278b strains employed
      here helped us identify fst1 and fst2 as mutations in the RasGAP genes IRA1 and
      IRA2. Cells lacking Ira1, Ira2, or Bcy1, the negative regulatory subunit of
      cyclic AMP (cAMP)-dependent protein kinase A (PKA), exhibited reduced Snf1
      pathway activation. Conversely, Snf1 activation was elevated in cells lacking the
      Gpr1 sugar receptor, which contributes to PKA signaling. We show that the Snf1
      activating kinase Sak1 is phosphorylated in vivo on a conserved serine (Ser1074)
      within an ideal PKA motif. However, this phosphorylation alone appears to play
      only a modest role in regulation, and Sak1 is not the only relevant target of the
      PKA pathway. Collectively, our results suggest that PKA, which integrates
      multiple regulatory inputs, could contribute to Snf1 regulation under various
      conditions via a complex mechanism. Our results also support the view that, like
      its mammalian counterpart, AMP-activated protein kinase (AMPK), yeast Snf1
      participates in metabolic checkpoint control that coordinates growth with
      nutrient availability.

PMID- 22140227
TI  - The Polo-like kinase PLKA in Aspergillus nidulans is not essential but plays
      important roles during vegetative growth and development.
AB  - The Polo-like kinases (Plks) are conserved, multifunctional cell cycle regulators
      that are induced in many forms of cancer and play additional roles in metazoan
      development. We previously identified plkA in Aspergillus nidulans, the only Plk
      investigated in filamentous fungi to date, and partially characterized its
      function through overexpression. Here, we report the plkA null phenotype.
      Surprisingly, plkA was not essential, unlike Plks in other organisms that contain
      a single homologue. A subset of cells lacking PLKA contained defects in spindle
      formation and chromosome organization, supporting some conservation in cell cycle
      function. However, septa were present, suggesting that PLKA, unlike other Plks,
      is not a central regulator of septation. Colonies lacking PLKA were compact with
      multibranched hyphae, implying a role for this factor in aspects of hyphal
      morphogenesis. These defects were suppressed by high temperature or low
      concentrations of benomyl, suggesting that PLKA may function during vegetative
      growth by influencing microtubule dynamics. However, the colonies also showed
      reduced conidiation and precocious formation of sexual Hulle cells in a benomyl-
      and temperature-insensitive manner. This result suggests that PLKA may influence
      reproduction through distinct mechanisms and represents the first example of a
      link between Plk function and development in fungi. Finally, filamentous fungal
      Plks have distinct features, and phylogenetic analyses reveal that they may group
      more closely with metazoan PLK4. In contrast, yeast Plks are more similar to
      metazoan proteins PLK1 to PLK3. Thus, A. nidulans PLKA shows some conservation in
      cell cycle function but may also play novel roles during hyphal morphogenesis and
      development.

PMID- 22140228
TI  - A machine learning approach to identify hydrogenosomal proteins in Trichomonas
      vaginalis.
AB  - The protozoan parasite Trichomonas vaginalis is the causative agent of
      trichomoniasis, the most widespread nonviral sexually transmitted disease in
      humans. It possesses hydrogenosomes-anaerobic mitochondria that generate H(2),
      CO(2), and acetate from pyruvate while converting ADP to ATP via substrate-level
      phosphorylation. T. vaginalis hydrogenosomes lack a genome and translation
      machinery; hence, they import all their proteins from the cytosol. To date,
      however, only 30 imported proteins have been shown to localize to the organelle.
      A total of 226 nuclear-encoded proteins inferred from the genome sequence harbor
      a characteristic short N-terminal presequence, reminiscent of mitochondrial
      targeting peptides, which is thought to mediate hydrogenosomal targeting. Recent
      studies suggest, however, that the presequences might be less important than
      previously thought. We sought to identify new hydrogenosomal proteins within the
      59,672 annotated open reading frames (ORFs) of T. vaginalis, independent of the N
      terminal targeting signal, using a machine learning approach. Our training set
      included 57 gene and protein features determined for all 30 known hydrogenosomal
      proteins and 576 nonhydrogenosomal proteins. Several classifiers were trained on
      this set to yield an import score for all proteins encoded by T. vaginalis ORFs,
      predicting the likelihood of hydrogenosomal localization. The machine learning
      results were tested through immunofluorescence assay and immunodetection in
      isolated cell fractions of 14 protein predictions using hemagglutinin constructs
      expressed under the homologous SCSalpha promoter in transiently transformed T.
      vaginalis cells. Localization of 6 of the 10 top predicted hydrogenosome
      localized proteins was confirmed, and two of these were found to lack an obvious
      N-terminal targeting signal.

PMID- 22140229
TI  - SWP5, a spore wall protein, interacts with polar tube proteins in the parasitic
      microsporidian Nosema bombycis.
AB  - Microsporidia are a group of eukaryotic intracellular parasites that infect
      almost all vertebrates and invertebrates. The microsporidian invasion process
      involves the extrusion of a unique polar tube into host cells. Both the spore
      wall and the polar tube play an important role in microsporidian pathogenesis. So
      far, five spore wall proteins (SWP1, SWP2, Enp1, Enp2, and EcCDA) from
      Encephalitozoon intestinalis and Encephalitozoon cuniculi and five spore wall
      proteins (SWP32, SWP30, SWP26, SWP25, and NbSWP5) from the silkworm pathogen
      Nosema bombycis have been identified. Here we report the identification and
      characterization of a spore wall protein (SWP5) with a molecular mass of 20.3 kDa
      in N. bombycis. This protein has low sequence similarity to other eukaryotic
      proteins. Immunolocalization analysis showed SWP5 localized to the exospore and
      the region of the polar tube in mature spores. Immunoprecipitation, mass
      spectrometry, and immunofluorescence analyses revealed that SWP5 interacts with
      the polar tube proteins PTP2 and PTP3. Anti-SWP5 serum pretreatment of mature
      spores significantly decreased their polar tube extrusion rate. Taken together,
      our results show that SWP5 is a spore wall protein localized to the spore wall
      and that it interacts with the polar tube, may play an important role in
      supporting the structural integrity of the spore wall, and potentially modulates
      the course of infection of N. bombycis.

PMID- 22140230
TI  - Transcription factor Efg1 shows a haploinsufficiency phenotype in modulating the
      cell wall architecture and immunogenicity of Candida albicans.
AB  - The Candida albicans transcription factor Efg1 is known to be involved in many
      different cellular processes, including morphogenesis, general metabolism, and
      virulence. Here we show that besides its manifold roles, Efg1 also has a
      prominent effect on cell wall structure and composition, strongly affecting the
      structural glucan part. Deletion of only one allele of EFG1 already results in
      severe phenotypes for cell wall biogenesis, comparable to those with deletion of
      both alleles, indicative of a severe haploinsufficiency for EFG1. The observed
      defects in structural setup of the cell wall, together with previously reported
      alterations in expression of cell surface proteins, result in altered immunogenic
      properties of strains with compromised Efg1 function. This is shown by
      interaction studies with macrophages and primary dendritic cells. The structural
      changes in the cell wall carbohydrate meshwork presented here, together with the
      manifold changes in cell wall protein composition and metabolism reported in
      other studies, contribute to the altered immune response mounted by innate immune
      cells and to the altered virulence phenotypes observed for strains lacking EFG1.

PMID- 22140232
TI  - Snf1-like protein kinase Ssp2 regulates glucose derepression in
      Schizosaccharomyces pombe.
AB  - The function of two fission yeast genes, SPCC74.03c/ssp2(+) and
      SPAC23H4.02/ppk9(+), encoding an Snf1-like protein kinase were investigated.
      Deletion of ssp2(+) caused a partial defect in glucose derepression of inv1(+),
      fbp1(+), and gld1(+) and in assimilation of sucrose and glycerol, while a
      mutation in ppk9(+) had no apparent effect. Scr1, a transcription factor involved
      in glucose repression, localized to the nucleus under glucose-rich conditions and
      to the cytoplasm during glucose starvation in wild-type cells. In contrast, in
      the ssp2Delta mutant, Scr1 localized to the nucleus in cells grown in glucose
      rich medium as well as in glucose-starved cells. Immunoblot analysis showed that
      Ssp2 is required for the phosphorylation of Scr1 upon glucose deprivation.
      Mutation of five putative Ssp2 recognition sites in Scr1 prevented glucose
      derepression of invertase in glucose-starved cells. These results indicate that
      Ssp2 regulates phosphorylation and subcellular localization of Scr1 in response
      to glucose.

PMID- 22140231
TI  - Adaptation of Cryptococcus neoformans to mammalian hosts: integrated regulation
      of metabolism and virulence.
AB  - The basidiomycete fungus Cryptococcus neoformans infects humans via inhalation of
      desiccated yeast cells or spores from the environment. In the absence of
      effective immune containment, the initial pulmonary infection often spreads to
      the central nervous system to result in meningoencephalitis. The fungus must
      therefore make the transition from the environment to different mammalian niches
      that include the intracellular locale of phagocytic cells and extracellular sites
      in the lung, bloodstream, and central nervous system. Recent studies provide
      insights into mechanisms of adaptation during this transition that include the
      expression of antiphagocytic functions, the remodeling of central carbon
      metabolism, the expression of specific nutrient acquisition systems, and the
      response to hypoxia. Specific transcription factors regulate these functions as
      well as the expression of one or more of the major known virulence factors of C.
      neoformans. Therefore, virulence factor expression is to a large extent embedded
      in the regulation of a variety of functions needed for growth in mammalian hosts.
      In this regard, the complex integration of these processes is reminiscent of the
      master regulators of virulence in bacterial pathogens.

PMID- 22140233
TI  - Heterogeneous expression of the virulence-related adhesin Epa1 between individual
      cells and strains of the pathogen Candida glabrata.
AB  - We investigated the relevance of gene expression heterogeneity to virulence
      properties of a major fungal pathogen, Candida glabrata. The organism's key
      virulence-associated factors include glycosylphosphatidylinositol-anchored
      adhesins, encoded subtelomerically by the EPA gene family. Individual-cell
      analyses of expression revealed very striking heterogeneity for Epa1, an adhesin
      that mediates ~95% of adherence to epithelial cells in vitro. The heterogeneity
      in Epa1 was markedly greater than that known for other yeast genes. Sorted cells
      expressing high or low levels of Epa1 exhibited high and low adherence to
      epithelial cells, indicating a link between gene expression noise and potential
      virulence. The phenotypes of sorted subpopulations reverted to mixed phenotypes
      within a few generations. Variation in single-cell Epa1 protein and mRNA levels
      was correlated, consistent with transcriptional regulation of heterogeneity. Sir
      dependent transcriptional silencing was the primary mechanism driving
      heterogeneous Epa1 expression in C. glabrata BG2, but not in CBS138 (ATCC 2001).
      Inefficient silencing in the latter strain was not due to a difference in EPA1
      sequence or (sub)telomere length and was overcome by ectopic SIR3 expression.
      Moreover, differences between strains in the silencing dependence of EPA1
      expression were evident across a range of clinical isolates, with heterogeneity
      being the greatest in strains where EPA1 was subject to silencing. The study
      shows how heterogeneity can impact the virulence-related properties of C.
      glabrata cell populations, with potential implications for microbial pathogenesis
      more broadly.

PMID- 22140234
TI  - Influence of age, race, sex, and body mass index on interpretation of midregional
      pro atrial natriuretic peptide for the diagnosis of acute heart failure: results
      from the BACH multinational study.
AB  - AIMS: Midregional pro atrial natriuretic peptide (MR-proANP) is useful for
      diagnosing acute heart failure (HF) in patients presenting to the Emergency
      Department with dyspnoea. Optimal interpretation of MR-proANP requires
      understanding of how various demographic variables influence its levels and
      performance as a diagnostic marker. We sought to determine how age, race, sex,
      and body mass index (BMI) affect the levels and interpretation of MR-proANP for
      the diagnosis of acute HF. METHODS AND RESULTS: The Biomarkers in Acute Heart
      Failure (BACH) study was an international 15-centre study of 1641 patients
      presenting to the Emergency Department with acute dyspnoea. Of these, 1352 had
      complete information on age, race, sex, and BMI. MR-proANP levels increased with
      age and were higher in men and in patients with lower BMI. MR-proANP performed
      better as a diagnostic marker in younger individuals and in blacks compared with
      whites. Despite this, MR-proANP at the recommended cut-off point of 120 pmol/L
      was >90 % sensitive in ruling out the diagnosis of acute HF in all subgroups of
      patients except white subjects <50 years old. CONCLUSION: Age, race, sex, and BMI
      affect MR-proANP levels to various degrees. However, the diagnostic performance
      of the recommended cut-off point of 120 pmol/L to rule out acute HF was robust
      across most subgroups. Although both sex and BMI affected MR-proANP levels, they
      did not alter its overall diagnostic performance. Lower cut-off points for MR
      proANP could be considered in younger patients and in patients with a higher BMI,
      to optimize diagnostic sensitivity.

PMID- 22140235
TI  - Ectopic expression of a wheat MYB transcription factor gene, TaMYB73, improves
      salinity stress tolerance in Arabidopsis thaliana.
AB  - MYB transcription factors (TFs) play pivotal roles in the abiotic stress response
      in plants, but their characteristics and functions in wheat (Triticum aestivum
      L.) have not been fully investigated. A novel wheat MYB TF gene, TaMYB73, is
      reported here based on the observation that its targeting probe showed the
      highest salinity-inducibility level among all probes annotated as MYB TFs in the
      cDNA microarray. TaMYB73 is a R2R3 type MYB protein with transactivation
      activity, and binds with types I, II, and IIG MYB binding motifs. The gene was
      induced by NaCl, dehydration, and several phytohormones, as well as some stress-,
      ABA-, and GA-responsive cis-elements present in its promoter region. Its over
      expression in Arabidopsis enhanced the tolerance to NaCl as well as to LiCl and
      KCl, whereas it had no contribution to mannitol tolerance. The over-expression
      lines had superior germination ability under NaCl and ABA treatments. The
      expression of many stress signalling genes such as AtCBF3 and AtABF3, as well as
      downstream responsive genes such as AtRD29A and AtRD29B, was improved in these
      over-expression lines, and TaMYB73 can bind with promoter sequences of AtCBF3 and
      AtABF3. Taken together, it is suggested that TaMYB73, a novel MYB transcription
      factor gene, participates in salinity tolerance based on improved ionic
      resistance partly via the regulation of stress-responsive genes.

PMID- 22140236
TI  - The cutting crew - ribonucleases are key players in the control of plastid gene
      expression.
AB  - Chloroplast biogenesis requires constant adjustment of RNA homeostasis under
      conditions of on-going developmental and environmental change and its regulation
      is achieved mainly by post-transcriptional control mechanisms mediated by various
      nucleus-encoded ribonucleases. More than 180 ribonucleases are annotated in
      Arabidopsis, but only 17 are predicted to localize to the chloroplast. Although
      different ribonucleases act at different RNA target sites in vivo, most nucleases
      that attack RNA are thought to lack intrinsic cleavage specificity and show non
      specific activity in vitro. In vivo, specificity is thought to be imposed by
      auxiliary RNA-binding proteins, including members of the huge pentatricopeptide
      repeat family, which protect RNAs from non-specific nucleolytic attack by masking
      otherwise vulnerable sites. RNA stability is also influenced by secondary
      structure, polyadenylation, and ribosome binding. Ribonucleases may cleave at
      internal sites (endonucleases) or digest successively from the 5' or 3' end of
      the polynucleotide chain (exonucleases). In bacteria, RNases act in the
      maturation of rRNA and tRNA precursors, as well as in initiating the degradation
      of mRNAs and small non-coding RNAs. Many ribonucleases in the chloroplasts of
      higher plants possess homologies to their bacterial counterparts, but their
      precise functions have rarely been described. However, many ribonucleases present
      in the chloroplast process polycistronic rRNAs, tRNAs, and mRNAs. The resulting
      production of monocistronic, translationally competent mRNAs may represent an
      adaptation to the eukaryotic cellular environment. This review provides a basic
      overview of the current knowledge of RNases in plastids and highlights gaps to
      stimulate future studies.

PMID- 22140237
TI  - Advances and remaining challenges in the transformation of barley and wheat.
AB  - Highly efficient and cost-effective transformation technologies are essential for
      studying gene function in the major cereal crops, wheat and barley. Demand for
      efficient transformation systems to allow over-expression, or RNAi-mediated
      silencing of target genes, is greatly increasing. This is due to technology
      advances, such as rapid genome sequencing, enhancing the rate of gene discovery
      and thus leading to a large number of genes requiring functional analysis through
      transformation pipelines. Barley can be transformed at very high efficiency but
      the methods are genotype-dependent. Wheat is more difficult to transform,
      however, recent advances are also allowing the development of high-throughput
      transformation systems in wheat. For many gene function studies, barley can be
      used as a model for wheat due to its highly efficient transformation rates and
      smaller, less complex genome. An ideal transformation system needs to be
      extremely efficient, simple to perform, inexpensive, genotype-independent, and
      give the required expression of the transgene. Considerable progress has been
      made in enhancing transformation efficiencies, controlling transgene expression
      and in understanding and manipulating transgene insertion. However, a number of
      challenges still remain, one of the key ones being the development of genotype
      independent transformation systems for wheat and barley.

PMID- 22140238
TI  - Arabidopsis mutants reveal that short- and long-term thermotolerance have
      different requirements for trienoic fatty acids.
AB  - The photosynthetic thylakoid has the highest level of lipid unsaturation of any
      membrane. In Arabidopsis thaliana plants grown at 22 degrees C, approximately 70%
      of the thylakoid fatty acids are trienoic - they have three double bonds. In
      Arabidopsis, and other species, the levels of trienoic fatty acids decline
      substantially at higher temperatures. Several genetic studies indicate that
      reduced unsaturation improves photosynthetic function and plant survival at high
      temperatures. Here, these studies are extended using the Arabidopsis triple
      mutant, fad3-2 fad7-2 fad8 that contains no detectable trienoic fatty acids. In
      the short-term, fluorescence analyses and electron-transport assays indicated
      that photosynthetic functions in this mutant are more thermotolerant than the
      wild type. However, long-term photosynthesis, growth, and survival of plants were
      all compromised in the triple mutant at high temperature. The fad3-2 fad7-2 fad8
      mutant is deficient in jasmonate synthesis and this hormone has been shown to
      mediate some aspects of thermotolerance; however, additional experiments
      demonstrated that a lack of jasmonate was not a major factor in the death of
      triple-mutant plants at high temperature. The results indicate that long-term
      thermotolerance requires a basal level of trienoic fatty acids. Thus, the success
      of genetic and molecular approaches to increase thermotolerance by reducing
      membrane unsaturation will be limited by countervailing effects that compromise
      essential plant functions at elevated temperatures.

PMID- 22140239
TI  - Peroxynitrite mediates programmed cell death both in papillar cells and in self
      incompatible pollen in the olive (Olea europaea L.).
AB  - Programmed cell death (PCD) has been found to be induced after pollination both
      in papillar cells and in self-incompatible pollen in the olive (Olea europaea
      L.). Reactive oxygen species (ROS) and nitric oxide (NO) are known to be produced
      in the pistil and pollen during pollination but their contribution to PCD has so
      far remained elusive. The possible role of ROS and NO was investigated in olive
      pollen-pistil interaction during free and controlled pollination and it was found
      that bidirectional interaction appears to exist between the pollen and the
      stigma, which seems to regulate ROS and NO production. Biochemical evidence
      strongly suggesting that both O(2)(-) and NO are essential for triggering PCD in
      self-incompatibility processes was also obtained. It was observed for the first
      time that peroxynitrite, a powerful oxidizing and nitrating agent generated
      during a rapid reaction between O(2)(-) and NO, is produced during pollination
      and that this is related to an increase in protein nitration which, in turn, is
      strongly associated with PCD. It may be concluded that peroxynitrite mediates PCD
      during pollen-pistil interaction in Olea europaea L. both in self-incompatible
      pollen and papillar cells.

PMID- 22140241
TI  - Dissection of the transcriptional regulation of grape ASR and response to glucose
      and abscisic acid.
AB  - Despite the fact that the precise physiological function of ASRs [abscisic acid
      (ABA), stress, ripening] remains unknown, they have been suggested to play a dual
      role in the plant response to environmental cues, as highly hydrophilic proteins
      for direct protection, as well as transcription factors involved in the
      regulation of gene expression. To investigate further the biological positioning
      of grape ASR in the hormonal and metabolic signal network, three promoters
      corresponding to its cDNA were isolated and submited to a detailed in silico and
      functional analysis. The results obtained provided evidence for the allelic
      polymorphism of the grape ASR gene, the organ-preferential expression conferred
      on the GUS reporter gene, and the specific phloem tissue localization revealed by
      in situ hybridization. The study of glucose and ABA signalling in its
      transcriptional control, by transfection of grape protoplasts using the dual
      luciferase system, revealed the complexity of ASR gene expression regulation. A
      model was proposed allowing a discussion of the place of ASR in the fine tuning
      of hormonal and metabolic signalling involved in the integration of environmental
      cues by the plant organism.

PMID- 22140240
TI  - CsFTL3, a chrysanthemum FLOWERING LOCUS T-like gene, is a key regulator of
      photoperiodic flowering in chrysanthemums.
AB  - Chrysanthemum is a typical short-day (SD) plant that responds to shortening
      daylength during the transition from the vegetative to the reproductive phase.
      FLOWERING LOCUS T (FT)/Heading date 3a (Hd3a) plays a pivotal role in the
      induction of phase transition and is proposed to encode a florigen. Three FT-like
      genes were isolated from Chrysanthemum seticuspe (Maxim.) Hand.-Mazz. f. boreale
      (Makino) H. Ohashi & Yonek, a wild diploid chrysanthemum: CsFTL1, CsFTL2, and
      CsFTL3. The organ-specific expression patterns of the three genes were similar:
      they were all expressed mainly in the leaves. However, their response to
      daylength differed in that under SD (floral-inductive) conditions, the expression
      of CsFTL1 and CsFTL2 was down-regulated, whereas that of CsFTL3 was up-regulated.
      CsFTL3 had the potential to induce early flowering since its overexpression in
      chrysanthemum could induce flowering under non-inductive conditions. CsFTL3
      dependent graft-transmissible signals partially substituted for SD stimuli in
      chrysanthemum. The CsFTL3 expression levels in the two C. seticuspe accessions
      that differed in their critical daylengths for flowering closely coincided with
      the flowering response. The CsFTL3 expression levels in the leaves were higher
      under floral-inductive photoperiods than under non-inductive conditions in both
      the accessions, with the induction of floral integrator and/or floral meristem
      identity genes occurring in the shoot apexes. Taken together, these results
      indicate that the gene product of CsFTL3 is a key regulator of photoperiodic
      flowering in chrysanthemums.

PMID- 22140242
TI  - ATH1 and KNAT2 proteins act together in regulation of plant inflorescence
      architecture.
AB  - The inflorescence of flowering plants is a highly organized structure, not only
      contributing to plant reproductive processes, but also constituting an important
      part of the entire plant morphology. Previous studies have revealed that the
      class-I KNOTTED1-like homeobox (KNOX) genes BREVIPEDICELLUS (BP or KNAT1), KNAT2,
      and KNAT6 play essential roles in inflorescence architecture. Pedicel morphology
      is known to contribute greatly to inflorescence architecture, and BP negatively
      regulates KNAT2 and KNAT6 to ensure that pedicels have a normal upward-pointing
      orientation. These findings indicate that a genetic network exists in controlling
      pedicel orientation, but how this network functions in the developmental process
      remains elusive. Here it is reported that the ARABIDOPSIS THALIANA HOMEOBOX GENE1
      (ATH1) gene, which belongs to the BELL1-like homeodomain gene family, is a new
      member participating in regulating pedicel orientation in the class-I KNOX
      network. In a genetic screening for suppressors of isoginchaku-2D, a gain-of
      function ASYMMETRIC LEAVES2 mutant that displays downward-pointing pedicels, a
      suppressor mutant was obtained. Characterization of this mutant revealed that the
      mutation corresponds to ATH1. Genetic analysis indicated that ATH1 acts mainly in
      the KNAT2 pathway. Yeast two-hybrid and bimolecular fluorescence complementation
      assays demonstrated that ATH1 physically interacts with KNAT2. The data indicate
      that the ATH1-KNAT2 complex acts redundantly with KNAT6, both of which are
      negatively regulated by BP during pedicel development.

PMID- 22140243
TI  - Cadmium interferes with auxin physiology and lignification in poplar.
AB  - Cadmium (Cd) is a phytotoxic heavy metal that causes rapid growth reduction. To
      investigate if Cd interferes with the metabolism of auxin, a major growth hormone
      in plants, poplars (Populus * canescens) expressing a heterologous GH3::GUS
      reporter gene were exposed to 50 MUM Cd in hydroponic solutions. Growth,
      photosynthetic performance, lignification, peroxidase activity, auxin
      concentration, and GUS staining were determined in order to record the activities
      of GH3 enzymes in the stem apex, the elongation zone, wood in the zone of radial
      growth, and in roots. Cd-induced growth reductions were tissue-specific
      decreasing in the order: roots>wood>shoot elongation and leaf initiation, whereas
      Cd concentrations increased in the order: leaves<wood<roots. Cd almost abolished
      the GH3 signal in the stem apex but caused strong increases in the vascular
      system of roots as well as in parenchymatic cells in the xylem. These changes
      were accompanied by increases in lignin and peroxidase activities and decreases
      in auxin concentrations. Since GH3 enzymes remove auxin from the active pool by
      conjugation and act as mediators between growth and defence, our data suggest
      that Cd stress triggered increases in GH3 activities which, in turn, depleted
      auxin in wood and thereby shunted the metabolism to enhanced formation of lignin.

PMID- 22140244
TI  - Multiple strategies to prevent oxidative stress in Arabidopsis plants lacking the
      malate valve enzyme NADP-malate dehydrogenase.
AB  - The nuclear-encoded chloroplast NADP-dependent malate dehydrogenase (NADP-MDH) is
      a key enzyme controlling the malate valve, to allow the indirect export of
      reducing equivalents. Arabidopsis thaliana (L.) Heynh. T-DNA insertion mutants of
      NADP-MDH were used to assess the role of the light-activated NADP-MDH in a
      typical C(3) plant. Surprisingly, even when exposed to high-light conditions in
      short days, nadp-mdh knockout mutants were phenotypically indistinguishable from
      the wild type. The photosynthetic performance and typical antioxidative systems,
      such as the Beck-Halliwell-Asada pathway, were barely affected in the mutants in
      response to high-light treatment. The reactive oxygen species levels remained
      low, indicating the apparent absence of oxidative stress, in the mutants. Further
      analysis revealed a novel combination of compensatory mechanisms in order to
      maintain redox homeostasis in the nadp-mdh plants under high-light conditions,
      particularly an increase in the NTRC/2-Cys peroxiredoxin (Prx) system in
      chloroplasts. There were indications of adjustments in extra-chloroplastic
      components of photorespiration and proline levels, which all could dissipate
      excess reducing equivalents, sustain photosynthesis, and prevent photoinhibition
      in nadp-mdh knockout plants. Such metabolic flexibility suggests that the malate
      valve acts in concert with other NADPH-consuming reactions to maintain a balanced
      redox state during photosynthesis under high-light stress in wild-type plants.

PMID- 22140245
TI  - Strategies for investigating the plant metabolic network with steady-state
      metabolic flux analysis: lessons from an Arabidopsis cell culture and other
      systems.
AB  - Steady-state (13)C metabolic flux analysis (MFA) is currently the experimental
      method of choice for generating flux maps of the compartmented network of primary
      metabolism in heterotrophic and mixotrophic plant tissues. While statistically
      robust protocols for the application of steady-state MFA to plant tissues have
      been developed by several research groups, the implementation of the method is
      still far from routine. The effort required to produce a flux map is more than
      justified by the information that it contains about the metabolic phenotype of
      the system, but it remains the case that steady-state MFA is both analytically
      and computationally demanding. This article provides an overview of principles
      that underpin the implementation of steady-state MFA, focusing on the definition
      of the metabolic network responsible for redistribution of the label,
      experimental considerations relating to data collection, the modelling process
      that allows a set of metabolic fluxes to be deduced from the labelling data, and
      the interpretation of flux maps. The article draws on published studies of
      Arabidopsis cell cultures and other systems, including developing oilseeds, with
      the aim of providing practical guidance and strategies for handling the issues
      that arise when applying steady-state MFA to the complex metabolic networks
      encountered in plants.

PMID- 22140246
TI  - Sugars, signalling, and plant development.
AB  - Like all organisms, plants require energy for growth. They achieve this by
      absorbing light and fixing it into a usable, chemical form via photosynthesis.
      The resulting carbohydrate (sugar) energy is then utilized as substrates for
      growth, or stored as reserves. It is therefore not surprising that modulation of
      carbohydrate metabolism can have profound effects on plant growth, particularly
      cell division and expansion. However, recent studies on mutants such as stimpy or
      ramosa3 have also suggested that sugars can act as signalling molecules that
      control distinct aspects of plant development. This review will focus on these
      more specific roles of sugars in development, and will concentrate on two major
      areas: (i) cross-talk between sugar and hormonal signalling; and (ii) potential
      direct developmental effects of sugars. In the latter, developmental mutant
      phenotypes that are modulated by sugars as well as a putative role for trehalose
      6-phosphate in inflorescence development are discussed. Because plant growth and
      development are plastic, and are greatly affected by environmental and
      nutritional conditions, the distinction between purely metabolic and specific
      developmental effects is somewhat blurred, but the focus will be on clear
      examples where sugar-related processes or molecules have been linked to known
      developmental mechanisms.

PMID- 22140247
TI  - Multi-dimensional regulation of metabolic networks shaping plant development and
      performance.
AB  - The metabolome is an integral part of a plant's life cycle and determines for a
      large part its external phenotype. It is the final, internal product of chemical
      interactions, obtained through developmental, genetic, and environmental inputs,
      and as such, it defines the state of a plant in terms of development and
      performance. Understanding its regulation will provide knowledge and new insights
      into the biochemical pathways and genetic interactions that shape the plant and
      its surroundings. In this review, we will focus on four dimensions that
      contribute to the huge diversity of metabolomes and we will illustrate how this
      diversity shapes the plant in terms of development and performance: (i) temporal
      regulation: the metabolome is extremely dynamic and temporal changes in the
      environment can have an immense impact on its composition; (ii) spatial
      regulation: metabolites can be very specific, in both quantitative and
      qualitative terms, to specialized organs, tissues, and cell types; (iii)
      environmental regulation: the metabolic profile of plants is highly dependent on
      environmental signals, such as light, temperature, and nutrients, and very
      susceptible to biotic and abiotic stresses; and (iv) genetic regulation: the
      biosynthesis, structure, and accumulation of metabolites have a genetic origin,
      and there is quantitative and qualitative variation for metabolomes within a
      species. We will address the contribution of these dimensions to the wide
      diversity of metabolomes and highlight how the multi-dimensional regulation of
      metabolism defines the plant's phenotype.

PMID- 22140248
TI  - Psychosocial factor exposures in the workplace: differences between immigrants
      and Spaniards.
AB  - BACKGROUND: The purpose of this study was to analyse psychosocial factor
      exposures in the workplace for immigrant workers in Spain and identify
      differences in exposure at work between immigrants and Spaniards. METHODS: A
      multi-stage sample was taken by conglomerates (final sample size: 7555 workers).
      The information was obtained in 2004 and 2005 using a standardized questionnaire
      administered by interviewing participants in their homes. The analysis focused on
      eight psychosocial factors. For quantitative demands and insecurity, the exposure
      was defined according to the higher third, and for the others, the exposure was
      defined according to the lower third. The prevalence ratio (PR) and confidence
      interval (CI) for unfavourable psychosocial factor, both crude and adjusted, were
      calculated using log binomial models. RESULTS: Those with highest prevalence of
      unfavourable psychosocial factor were immigrant manual workers, particularly in
      low possibilities for development (PR=2.87; 95% CI 2.44-3.73), and immigrant
      women, particularly in low control over working times (PR=1.72; 95% CI 1.55
      1.91). CONCLUSIONS: Immigrant workers with manual jobs and immigrant women are
      the groups most exposed to psychosocial factor. In efforts to prevent these
      exposures, these inequalities should be taken into account.

PMID- 22140249
TI  - Quality evaluation of guidelines on genetic screening, surveillance and
      management of hereditary colorectal cancer.
AB  - BACKGROUND: We examined the methodological quality of guidelines on colorectal
      cancer genetic susceptibility syndromes. METHODS: PubMed, EMBASE, and Google were
      searched up to July 2010. Adjourned guidelines in English were included. The
      Appraisal of Guidelines, Research and Evaluation (AGREE) instrument was used to
      assess their quality, and the reported evidence base of the guidelines was
      evaluated. RESULTS: The search yielded 17 eligible guidelines: 11 were developed
      by independent associations, while 6 had national?state endorsement. Only three
      guidelines performed satisfactorily, achieving a score >50% in all 6 AGREE
      domains. Mean standardized scores for the 6 AGREE domains were: 'scope and
      purpose', 83.9 +/- 22.5%; 'stakeholder involvement', 35.6 +/- 24.9%; 'rigour of
      development', 48.6 +/- 25.3%; 'clarity and presentation', 71.6 +/- 19.3%;
      'applicability', 33.8 +/- 30.1%; 'editorial independence', 42.2 +/- 39.7%.
      Guidelines with national endorsement performed better in all the domains, with a
      statistically significant difference in three domains. Fifteen guidelines out of
      17 were found to be based on research evidence. CONCLUSIONS: There is scope, in
      many areas, for improving the guidelines analysed, among which are the
      involvement of various professional figures and patients' representatives, and
      policies for their application. The AGREE instrument is a useful tool and could
      also be used profitably by guideline developers to improve the quality of
      recommendations.

PMID- 22140250
TI  - Front-of-pack nutrition labelling: are multiple formats a problem for consumers?
AB  - BACKGROUND: Nutrition labels are a potentially valuable tool to assist consumers
      in making healthy food choices. Front-of-pack labels are a relatively new format
      and are now widely used across many European countries, but it is unclear which
      of the many formats in use are best understood by consumers. It is also unclear
      whether the existence of multiple formats impedes understanding and use. This
      article addresses this question with findings from a study commissioned by the UK
      Food Standards Agency to provide evidence to inform policy decisions in this
      area. METHODS: In-depth qualitative interviews were used to explore consumers'
      decision-making processes when using two different front-of-pack label formats to
      judge the relative healthiness of a pair of products. Participants were presented
      with product pairs differently labelled and a series of structured prompts were
      used to access their internal dialogues and to identify any difficulties
      encountered. RESULTS: The interviews revealed that making product comparisons
      using different label formats was challenging for participants and particularly
      for those product pairs where there was not an obvious answer. When the label
      formats on the product pairs lacked a common element, such as text, this also
      caused difficulties and misinterpretation. The comparisons also took time and
      effort that would be a deterrent in real-life situations. CONCLUSIONS: These
      findings indicate that the existence of multiple front-of-pack label formats in
      the marketplace may impede consumer comprehension and discourage use. They
      suggest that a single format may encourage consumers to use front-of-pack labels
      in making healthy food choices.

PMID- 22140251
TI  - The validity of indicators for assessing quality of care: a review of the
      European literature on hospital readmission rate.
AB  - BACKGROUND: Quality indicators are increasingly being implemented in Europe for
      policy and management purposes. Many of these indicators were initially developed
      and implemented in the USA. However, the suitability of directly adopting
      indicators that have been developed in a different health care system can be
      questioned. Therefore, we investigate the validity behind the readmission rate
      indicator in the European setting. METHODS: A systematic literature study was
      conducted to identify the status of scientific research on the validity of this
      indicator (January 1999 and April 2010). Descriptive information as well as
      information on the data source, indicator definition, risk adjustment factors,
      and conclusions was assessed. RESULTS: The majority of the 486 included studies
      focused on the actual use of the indicator as an outcome measure in European
      countries. Only 21 studies specifically addressed its validity, or important
      prerequisites of validity. There is little consensus over the time-frame used to
      calculate the indicator, the type of readmission that is included, and the case
      mix adjustment applied. CONCLUSIONS: Despite the increase in Europe of the use of
      the readmission rate as a measure of quality of care, the amount of research
      performed on its validity is scarce. Those studies that report on validity
      replicate earlier, mainly US findings (<1999) of methodological problems and
      express reservations on its large-scale use. The readmission rate as an indicator
      should be used with care. Users should address issues related to definition, time
      frame and case-mix adjustment as part of the process to enhance validity in the
      European settings.

PMID- 22140252
TI  - Genetic differentiation among migrant and resident populations of the threatened
      Asian houbara bustard.
AB  - The Asian houbara bustard Chlamydotis macqueenii is a partial migrant of
      conservation concern found in deserts of central Asia and the Middle East. In the
      southern part of the species range, resident populations have been greatly
      fragmented and reduced by sustained human pressure. In the north, birds migrate
      from breeding grounds between West Kazakhstan and Mongolia to wintering areas in
      the Middle East and south central Asia. Extensive satellite tracking has shown
      substantial partitioning in migration routes and wintering grounds, suggesting a
      longitudinal barrier to present-day gene flow among migrants. In this context, we
      explored genetic population structure using 17 microsatellite loci and sampling
      108 individuals across the range. We identified limited but significant overall
      differentiation (F(CT) = 0.045), which was overwhelmingly due to the
      differentiation of resident Arabian populations, particularly the one from Yemen,
      relative to the central Asian populations. Population structure within the
      central Asian group was not detectable with the exception of subtle
      differentiation of West Kazakh birds on the western flyway, relative to eastern
      populations. We interpret these patterns as evidence of recent common ancestry in
      Asia, coupled with a longitudinal barrier to present-day gene flow along the
      migratory divide, which has yet to translate into genetic divergence. These
      results provide key parameters for a coherent conservation strategy aimed at
      preserving genetic diversity and migration routes.

PMID- 22140253
TI  - Variation in the tyrosinase gene associated with a white humpback whale
      (Megaptera novaeangliae).
AB  - Tyrosinase-negative oculocutaneous albinism (OCA1A) is characterized by lifelong
      white hair and skin, a phenotype that has been described in most mammalian
      species worldwide. Tyrosinase is the key enzyme in melanin biosynthesis, and
      mutations in the tyrosinase gene result in OCA1A. We examined sequence variation
      at exon 1 of the tyrosinase gene in 66 humpback whale samples collected from the
      east coast of Australia, including an anomalously white humpback whale known as
      "Migaloo." We identified 3 novel variants, including a cytosine deletion that
      results in a premature stop codon in exon 1. The deletion truncates the
      tyrosinase protein including the putative catalytic domains that are essential
      for tyrosinase enzymatic activity. Migaloo was homozygous for this deletion,
      suggesting that the albino phenotype is a consequence of inactive tyrosinase
      caused by the frameshift in the tyrosinase gene.

PMID- 22140254
TI  - Minimal tolerance to a tumor antigen encoded by a cancer-germline gene.
AB  - Central tolerance toward tissue-restricted Ags is considered to rely on ectopic
      expression in the thymus, which was also observed for tumor Ags encoded by cancer
      germline genes. It is unknown whether endogenous expression shapes the T cell
      repertoire against the latter Ags and explains their weak immunogenicity. We
      addressed this question using mouse cancer-germline gene P1A, which encodes
      antigenic peptide P1A(35-43) presented by H-2L(d). We made P1A-knockout (P1A-KO)
      mice and asked whether their anti-P1A(35-43) immune responses were stronger than
      those of wild-type mice and whether P1A-KO mice responded to other P1A epitopes,
      against which wild-type mice were tolerized. We observed that both types of mice
      mounted similar P1A(35-43)-specific CD8 T cell responses, although the frequency
      of P1A(35-43)-specific CD8 T cells generated in response to P1A-expressing tumors
      was slightly higher in P1A-KO mice. This higher reactivity allowed naive P1A-KO
      mice to reject spontaneously P1A-expressing tumors, which progressed in wild-type
      mice. TCR-Vbeta usage of P1A(35-43)-specific CD8 cells was slightly modified in
      P1A-KO mice. Peptide P1A(35-43) remained the only P1A epitope recognized by CD8 T
      cells in both types of mice, which also displayed similar thymic selection of a
      transgenic TCR recognizing P1A(35-43). These results indicate the existence of a
      minimal tolerance to an Ag encoded by a cancer-germline gene and suggest that its
      endogenous expression only slightly affects diversification of the T cell
      repertoire against this Ag.

PMID- 22140256
TI  - Cytosolic DNA triggers mitochondrial apoptosis via DNA damage signaling proteins
      independently of AIM2 and RNA polymerase III.
AB  - A key host response to limit microbial spread is the induction of cell death when
      foreign nucleic acids are sensed within infected cells. In mouse macrophages,
      transfected DNA or infection with modified vaccinia virus Ankara (MVA) can
      trigger cell death via the absent in melanoma 2 (AIM2) inflammasome. In this
      article, we show that nonmyeloid human cell types lacking a functional AIM2
      inflammasome still die in response to cytosolic delivery of different DNAs or
      infection with MVA. This cell death induced by foreign DNA is independent of
      caspase-8 and carries features of mitochondrial apoptosis: dependence on BAX,
      APAF-1, and caspase-9. Although it does not require the IFN pathway known to be
      triggered by infection with MVA or transfected DNA via polymerase III and
      retinoid acid-induced gene I-like helicases, it shows a strong dependence on
      components of the DNA damage signaling pathway: cytosolic delivery of DNA or
      infection with MVA leads to phosphorylation of p53 (serines 15 and 46) and
      autophosphorylation of ataxia telangiectasia mutated (ATM); depleting p53 or ATM
      with small interfering RNA or inhibiting the ATM/ATM-related kinase family by
      caffeine strongly reduces apoptosis. Taken together, our findings suggest that a
      pathway activating DNA damage signaling plays an important independent role in
      detecting intracellular foreign DNA, thereby complementing the induction of IFN
      and activation of the AIM2 inflammasome.

PMID- 22140255
TI  - Skin mast cells protect mice against vaccinia virus by triggering mast cell
      receptor S1PR2 and releasing antimicrobial peptides.
AB  - Mast cells (MCs) are well-known effectors of allergic reactions and are
      considered sentinels in the skin and mucosa. In addition, through their
      production of cathelicidin, MCs have the capacity to oppose invading pathogens.
      We therefore hypothesized that MCs could act as sentinels in the skin against
      viral infections using antimicrobial peptides. In this study, we demonstrate that
      MCs react to vaccinia virus (VV) and degranulate using a membrane-activated
      pathway that leads to antimicrobial peptide discharge and virus inactivation.
      This finding was supported using a mouse model of viral infection. MC-deficient
      (Kit(wsh-/-)) mice were more susceptible to skin VV infection than the wild type
      animals, whereas Kit(wsh-/-) mice reconstituted with MCs in the skin showed a
      normal response to VV. Using MCs derived from mice deficient in cathelicidin
      antimicrobial peptide, we showed that antimicrobial peptides are one important
      antiviral granule component in in vivo skin infections. In conclusion, we
      demonstrate that MC presence protects mice from VV skin infection, MC
      degranulation is required for protecting mice from VV, neutralizing Ab to the L1
      fusion entry protein of VV inhibits degranulation apparently by preventing S1PR2
      activation by viral membrane lipids, and antimicrobial peptide release from MC
      granules is necessary to inactivate VV infectivity.

PMID- 22140258
TI  - A structural basis for varied alphabeta TCR usage against an immunodominant EBV
      antigen restricted to a HLA-B8 molecule.
AB  - EBV is a ubiquitous and persistent human pathogen, kept in check by the cytotoxic
      T cell response. In this study, we investigated how three TCRs, which differ in
      their T cell immunodominance hierarchies and gene usage, interact with the same
      EBV determinant (FLRGRAYGL), bound to the same Ag-presenting molecule, HLA-B8. We
      found that the three TCRs exhibit differing fine specificities for the viral Ag.
      Further, via structural and biophysical approaches, we demonstrated that the
      viral Ag provides the greatest energetic contribution to the TCR-peptide-HLA
      interaction, while focusing on a few adjacent HLA-based interactions to further
      tune fine-specificity requirements. Thus, the TCR engages the peptide-HLA with
      the viral Ag as the main glue, such that neighboring TCR-MHC interactions are
      recruited as a supportive adhesive. Collectively, we provide a portrait of how
      the host's adaptive immune response differentially engages a common viral Ag.

PMID- 22140257
TI  - Lamin B receptor regulates the growth and maturation of myeloid progenitors via
      its sterol reductase domain: implications for cholesterol biosynthesis in
      regulating myelopoiesis.
AB  - Lamin B receptor (LBR) is a bifunctional nuclear membrane protein with N-terminal
      lamin B and chromatin-binding domains plus a C-terminal sterol Delta(14)
      reductase domain. LBR expression increases during neutrophil differentiation, and
      deficient expression disrupts neutrophil nuclear lobulation characteristic of
      Pelger-Huet anomaly. Thus, LBR plays a critical role in regulating myeloid
      differentiation, but how the two functional domains of LBR support this role is
      currently unclear. We previously identified abnormal proliferation and deficient
      functional maturation of promyelocytes (erythroid, myeloid, and lymphoid [EML]
      derived promyelocytes) derived from EML-ic/ic cells, a myeloid model of
      ichthyosis (ic) bone marrow that lacks Lbr expression. In this study, we provide
      new evidence that cholesterol biosynthesis is important to myeloid cell growth
      and is supported by the sterol reductase domain of Lbr. Cholesterol biosynthesis
      inhibitors caused growth inhibition of EML cells that increased in EML-derived
      promyelocytes, whereas cells lacking Lbr exhibited complete growth arrest at both
      stages. Lipid production increased during wild-type neutrophil maturation, but
      ic/ic cells exhibited deficient levels of lipid and cholesterol production.
      Ectopic expression of a full-length Lbr in EML-ic/ic cells rescued both nuclear
      lobulation and growth arrest in cholesterol starvation conditions. Lipid
      production also was rescued, and a deficient respiratory burst was corrected.
      Expression of just the C-terminal sterol reductase domain of Lbr in ic/ic cells
      also improved each of these phenotypes. Our data support the conclusion that the
      sterol Delta(14) reductase domain of LBR plays a critical role in cholesterol
      biosynthesis and that this process is essential to both myeloid cell growth and
      functional maturation.

PMID- 22140259
TI  - Acquisition of complement factor H is important for pathogenesis of Streptococcus
      pyogenes infections: evidence from bacterial in vitro survival and human genetic
      association.
AB  - Streptococcus pyogenes (or group A streptococcus [GAS]) is a major human pathogen
      causing infections, such as tonsillitis, erysipelas, and sepsis. Several GAS
      strains bind host complement regulator factor H (CFH) via its domain 7 and,
      thereby, evade complement attack and C3b-mediated opsonophagocytosis. Importance
      of CFH binding for survival of GAS has been poorly studied because removal of CFH
      from plasma or blood causes vigorous complement activation, and specific
      inhibitors of the interaction have not been available. In this study, we found
      that activation of human complement by different GAS strains (n = 38) correlated
      negatively with binding of CFH via its domains 5-7. The importance of acquisition
      of host CFH for survival of GAS in vitro was studied next by blocking the binding
      with recombinant CFH5-7 lacking the regulatory domains 1-4. Using this fragment
      in full human blood resulted in death or radically reduced multiplication of all
      of the studied CFH-binding GAS strains. To study the importance of CFH binding in
      vivo (i.e., for pathogenesis of streptococcal infections), we used our recent
      finding that GAS binding to CFH is diminished in vitro by polymorphism 402H,
      which is also associated with age-related macular degeneration. We showed that
      allele 402H is suggested to be associated with protection from erysipelas (n =
      278) and streptococcal tonsillitis (n = 209) compared with controls (n = 455) (p
      < 0.05). Taken together, the bacterial in vitro survival data and human genetic
      association revealed that binding of CFH is important for pathogenesis of GAS
      infections and suggested that inhibition of CFH binding can be a novel
      therapeutic approach in GAS infections.

PMID- 22140260
TI  - Recruitment of a distinct but related set of VH sequences into the murine
      CD21hi/CD23- marginal zone B cell repertoire to that seen in the class-switched
      antibody response.
AB  - Development and maintenance of cells in the murine follicular and marginal zone
      compartments is thought to involve differing levels of stimulation of the BCR,
      although it is still not clear which BCR ligands mediate these events. How the
      delineation between naive and Ag experienced B cell populations relates to cell
      phenotype and how precise or blurred this delineation is, is also not well
      understood. In this study, using PCR to analyze the Ab response to phenyl
      oxazolone in the mouse, we show that the Ab repertoire of CD21(hi)/CD23(-)
      marginal zone B cells shows persistent increase in levels of particular IgM after
      immunization with foreign Ag. Further, we show that these IgMs have different but
      related VH/CDR3 sequences from those seen in the class-switched response to
      oxazolone that we have also analyzed. We also detect an effect of Ag on the
      follicular B cell repertoire that is less persisting. These results provide
      evidence consistent with the signal-strength model of mature B cell development
      being extended to include stimulation by foreign Ag, and also further the known
      zone of influence of foreign Ag on the B cell compartment.

PMID- 22140261
TI  - The role of Gr1+ cells after anti-CD20 treatment in type 1 diabetes in nonobese
      diabetic mice.
AB  - Studies suggest that Gr1(+)CD11b(+) cells have immunoregulatory function, and
      these cells may play an important role in autoimmune diseases. In this study, we
      investigated the regulatory role of Gr1(+)CD11b(+) cells in protecting against
      type 1 diabetes in NOD mice. In this study, we showed that temporary B cell
      depletion induced the expansion of Gr1(+)CD11b(+) cells. Gr1(+)CD11b(+) cells not
      only directly suppress diabetogenic T cell function but also can induce
      regulatory T cell differentiation in a TGF-beta-dependent manner. Furthermore, we
      found that Gr1(+)CD11b(+) cells could suppress diabetogenic CD4 and CD8 T cell
      function in an IL-10-, NO-, and cell contact-dependent manner. Interestingly,
      single anti-Gr1 mAb treatment can also induce a transient expansion of
      Gr1(+)CD11b(+) cells that delayed diabetes development in NOD mice. Our data
      suggest that Gr1(+)CD11b(+) cells contribute to the establishment of immune
      tolerance to pancreatic islet autoimmunity. Manipulation of Gr1(+)CD11b(+) cells
      could be considered as a novel immunotherapy for the prevention of type 1
      diabetes.

PMID- 22140263
TI  - Myeloid cell IL-10 production in response to leishmania involves inactivation of
      glycogen synthase kinase-3beta downstream of phosphatidylinositol-3 kinase.
AB  - Leishmania disease expression has been linked to IL-10. In this study, we
      investigated the regulation of IL-10 production by macrophages infected with
      Leishmania donovani. Infection of either murine or human macrophages brought
      about selective phosphorylation of Akt-2 in a PI3K-dependent manner. These events
      were linked to phosphorylation and inactivation of glycogen synthase kinase-3beta
      (GSK-3beta) at serine 9, as the latter was abrogated by inhibition of either PI3K
      or Akt. One of the transcription factors that is negatively regulated by GSK
      3beta is CREB, which itself positively regulates IL-10 expression. Infection of
      macrophages with leishmania induced phosphorylation of CREB at serine 133, and
      this was associated with enhanced CREB DNA binding activity and induction of IL
      10. Similar to phosphorylation of GSK-3beta, both phosphorylation of CREB at
      serine 133 and CREB DNA binding activity were abrogated in cells treated with
      inhibitors of either PI3K or Akt prior to infection. Furthermore, disruption of
      this pathway either by inhibition of Akt or by overexpression of GSK-3beta
      markedly attenuated IL-10 production in response to leishmania. Thus, GSK-3beta
      negatively regulates myeloid cell IL-10 production in response to leishmania.
      Switching off GSK-3beta promotes disease pathogenesis.

PMID- 22140262
TI  - The cytokine midkine and its receptor RPTPzeta regulate B cell survival in a
      pathway induced by CD74.
AB  - Lasting B cell persistence depends on survival signals that are transduced by
      cell surface receptors. In this study, we describe a novel biological mechanism
      essential for survival and homeostasis of normal peripheral mature B cells and
      chronic lymphocytic leukemia cells, regulated by the heparin-binding cytokine,
      midkine (MK), and its proteoglycan receptor, the receptor-type tyrosine
      phosphatase zeta (RPTPzeta). We demonstrate that MK initiates a signaling cascade
      leading to B cell survival by binding to RPTPzeta. In mice lacking PTPRZ, the
      proportion and number of the mature B cell population are reduced. Our results
      emphasize a unique and critical function for MK signaling in the previously
      described MIF/CD74-induced survival pathway. Stimulation of CD74 with MIF leads
      to c-Met activation, resulting in elevation of MK expression in both normal mouse
      splenic B and chronic lymphocytic leukemia cells. Our results indicate that MK
      and RPTPzeta are important regulators of the B cell repertoire. These findings
      could pave the way toward understanding the mechanisms shaping B cell survival
      and suggest novel therapeutic strategies based on the blockade of the MK/RPTPzeta
      dependent survival pathway.

PMID- 22140264
TI  - Molecular determinants of HIV-2 R5-X4 tropism in the V3 loop: development of a
      new genotypic tool.
AB  - OBJECTIVE: The use of CCR5 inhibitors requires a tool to predict human
      immunodeficiency virus type 2 (HIV-2) tropism, as established in HIV-1. The aim
      of our study was to identify genotypic determinants of HIV-2 tropism located in
      the gp105 V3 loop. METHODS: HIV-2 tropism phenotypic assays were performed on 53
      HIV-2 clinical isolates using GFP expressing human osteosarcoma T4 [GHOST(3)]
      cell lines expressing CD4 and CCR5 or CXCR4 coreceptors. The gp105 V3 loop was
      sequenced and analyzed. RESULTS: Thirty-four HIV-2 isolates were classified as
      R5, 7 as X4, and 12 as X4/R5 (dual). Substitution at residue 18 was always
      associated with a dual/X4 tropism (P < .00001). The following determinants were
      associated with dual/X4 tropism: a global net charge of more than +6 (P <
      .00001), V19K/R mutation (P < .00001), S22A/F/Y mutation (P < .002), Q23R
      mutation (P < .00001), and insertions at residue 24 (P < .00001), I25L/Y (P <
      .0004), R28K (P < .0004), and R30K (P < .014). These mutations were not found in
      R5 isolates, except R28K and R30K, which were detected in 4 and 5 R5 isolates,
      respectively. The 4 major genotypic determinants of dual/X4 tropism were mutation
      at residue 18, V19 K/R mutation, insertions at residue 24, and V3 global net
      charge. CONCLUSIONS: We established a strong association between HIV-2 phenotypic
      tropism and V3-loop sequences, allowing for the prediction of R5- and/or X4
      tropic viruses in HIV-2 infection.

PMID- 22140265
TI  - Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first
      half of pregnancy--a case-control study of the outcome in children.
AB  - BACKGROUND: Primary cytomegalovirus (CMV) infection early in gestation causes
      severe disease. METHODS: Case patients were 32 congenitally infected children
      aged 1-5 years who had either hearing deficit and/or psychomotor retardation and
      whose mothers had a confirmed or probable primary CMV infection at <= 20 weeks'
      gestation. Control subjects were 32 congenitally infected normal children whose
      mothers had a confirmed primary infection at <= 20 weeks' gestation. Case
      patients and control subjects were matched by the weeks of maternal gestation (+/
      1 week) at the mother's infection and by the child's age (+/- 1 year) at
      evaluation. RESULTS: For the case patients and control subjects, the mean age was
      3.0 years. The mean number of weeks of gestation at maternal infection was 11
      weeks. The only risk factor for an affected child was the mother not receiving
      immunoglobulin (P = .001). Of the 32 case patients, only 4 mothers received CMV
      immunoglobulin, compared with 27 of the 32 mothers of control infants (adjusted
      odds ratio, 14 [95% confidence interval, 1.7-110]). The rate of both psychomotor
      retardation and hearing deficit decreased with immunoglobulin. CONCLUSIONS: These
      results support the efficacy of immunoglobulins for decreasing the severity of
      disabilities caused by fetal CMV infection after a primary maternal infection
      during pregnancy.

PMID- 22140266
TI  - The monomer-dimer equilibrium and glycosaminoglycan interactions of chemokine
      CXCL8 regulate tissue-specific neutrophil recruitment.
AB  - Chemokines exert their function by binding the GPCR class of receptors on
      leukocytes and cell surface GAGs in target tissues. Most chemokines reversibly
      exist as monomers and dimers, but very little is known regarding the molecular
      mechanisms by which the monomer-dimer equilibrium modulates in vivo function. For
      the chemokine CXCL8, we recently showed in a mouse lung model that monomers and
      dimers are active and that the monomer-dimer equilibrium of the WT plays a
      crucial role in regulating neutrophil recruitment. In this study, we show that
      monomers and dimers are also active in the mouse peritoneum but that the role of
      monomer-dimer equilibrium is distinctly different between these tissues and that
      mutations in GAG-binding residues render CXCL8 less active in the peritoneum but
      more active in the lung. We propose that tissue-specific differences in chemokine
      gradient formation, resulting from tissue-specific differences in GAG
      interactions, are responsible for the observed differences in neutrophil
      recruitment. Our observation of differential roles played by the CXCL8 monomer
      dimer equilibrium and GAG interactions in different tissues is novel and reveals
      an additional level of complexity of how chemokine dimerization regulates in vivo
      recruitment.

PMID- 22140267
TI  - IL-10-induced gp130 expression in mouse mast cells permits IL-6 trans-signaling.
AB  - It is reported that human and mouse mast cells express the IL-27R, which consists
      of WSX-1 (the IL-27Ralpha subunit) and the signal-transducing subunit gp130.
      Although it has been proposed that IL-27 may negatively regulate mast cell
      dependent, immediate hypersensitivity responses directly, this has yet to be
      examined specifically. We found that mouse BMMC and primary peritoneal mast cells
      are unresponsive to IL-27. Consistent with this, gp130 protein in resting BMMC
      was not on the cell surface to a measurable degree but was found intracellularly,
      and data are consistent with incompletely processed N-linked glycosylation.
      Furthermore, BMMC constitutively expressed SOCS3, a major negative regulator of
      gp130 signaling. However, BMMC stimulation with IL-10 and consequential STAT3
      activation increased gp130 expression, which resulted in a functional gp130
      receptor on the BMMC cell surface. IL-10 has not been previously shown to
      regulate gp130 expression, which on the BMMC surface, permitted IL-6 trans
      signaling, found to increase survival under limiting conditions and enhance IL-13
      and TNF-alpha secretion. This study identifies factors that regulate mouse mast
      cell gp130 expression and signaling and makes conspicuous the limitations of
      using cultured mouse mast cells to study the effects of the IL-6/IL-12 cytokine
      family on mast cell biology.

PMID- 22140270
TI  - Emerging topics and new perspectives on regulatory and effector T cells.

PMID- 22140269
TI  - The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and
      energy metabolism in healthy women and men.
AB  - Fasting promotes triglyceride (TG) accumulation in lean tissues of some animals,
      but the effect in humans is unknown. Additionally, fasting lipolysis is sexually
      dimorphic in humans, suggesting that lean tissue TG accumulation and metabolism
      may differ between women and men. This study investigated lean tissue TG content
      and metabolism in women and men during extended fasting. Liver and muscle TG
      content were measured by magnetic resonance spectroscopy during a 48-h fast in
      healthy men and women. Whole-body and hepatic carbohydrate, lipid, and energy
      metabolism were also evaluated using biochemical, calorimetric, and stable
      isotope tracer techniques. As expected, postabsorptive plasma fatty acids (FAs)
      were higher in women than in men but increased more rapidly in men with the onset
      of early starvation. Concurrently, sexual dimorphism was apparent in lean tissue
      TG accumulation during the fast, occurring in livers of men but in muscles of
      women. Despite differences in lean tissue TG distribution, men and women had
      identical fasting responses in whole-body and hepatic glucose and oxidative
      metabolism. In conclusion, TG accumulated in livers of men but in muscles of
      women during extended fasting. This sexual dimorphism was related to differential
      fasting plasma FA concentrations but not to whole body or hepatic utilization of
      this substrate.

PMID- 22140271
TI  - EMT and MET as paradigms for cell fate switching.
AB  - Cell fate determination is a major unsolved problem in cell and developmental
      biology. The discovery of reprogramming by pluripotent factors offers a rational
      system to investigate the molecular mechanisms associated with cell fate
      decisions. The idea that reprogramming of fibroblasts starts with a mesenchymal
      epithelial transition (MET) suggests that the process is perhaps a reversal of
      epithelial to mesenchymal transition (EMT) found frequently during early
      embryogenesis. As such, we believe that investigations into MET-EMT may yield
      detailed molecular insights into cell fate decisions, not only for the switching
      between epithelial and mesenchymal cells, but also other cell types.

PMID- 22140268
TI  - Adipose tissue stem cells meet preadipocyte commitment: going back to the future.
AB  - White adipose tissue (WAT) is perhaps the most plastic organ in the body, capable
      of regeneration following surgical removal and massive expansion or contraction
      in response to altered energy balance. Research conducted for over 70 years has
      investigated adipose tissue plasticity on a cellular level, spurred on by the
      increasing burden that obesity and associated diseases are placing on public
      health globally. This work has identified committed preadipocytes in the stromal
      vascular fraction of adipose tissue and led to our current understanding that
      adipogenesis is important not only for WAT expansion, but also for maintenance of
      adipocyte numbers under normal metabolic states. At the turn of the millenium,
      studies investigating preadipocyte differentiation collided with developments in
      stem cell research, leading to the discovery of multipotent stem cells within
      WAT. Such adipose tissue-derived stem cells (ASCs) are capable of differentiating
      into numerous cell types of both mesodermal and nonmesodermal origin, leading to
      their extensive investigation from a therapeutic and tissue engineering
      perspective. However, the insights gained through studying ASCs have also
      contributed to more-recent progress in attempts to better characterize committed
      preadipocytes in adipose tissue. Thus, ASC research has gone back to its roots,
      thereby expanding our knowledge of preadipocyte commitment and adipose tissue
      biology.

PMID- 22140273
TI  - Photocatalytic Water Oxidation Using Manganese Compounds Immobilized in Nafion
      Polymer Membranes.
AB  - Robust water oxidation catalysts using earth abundant metals are required as part
      of an overall scheme to convert sunlight into fuels. Here, we report the
      immobilization of [[Formula: see text]O(5)(terpy)(4)(H(2)O)(2)](ClO(4))(6) (terpy
      = 2,2';6',2"-terpyridine), [Mn(4)O(6)(tacn)(4)](ClO(4))(4) (tacn = 1,4,7
      triazacyclononane), and manganese dioxide nanoparticles in Nafion on fluorine
      doped tin oxide conducting glass electrodes. The electrodes are illuminated with
      white light in the presence of an applied potential and the resulting
      photocurrent is assigned to the oxidation of solvent water. Photodecomposition of
      the tetrameric complexes results in a material that is more active for light
      driven electrooxidation of water. The reactivity, wavelength dependence, and
      stability of the compounds in Nafion under illumination are discussed.

PMID- 22140272
TI  - A genome-wide association study of men with symptoms of testicular dysgenesis
      syndrome and its network biology interpretation.
AB  - BACKGROUND: Testicular dysgenesis syndrome (TDS) is a common disease that links
      testicular germ cell cancer, cryptorchidism and some cases of hypospadias and
      male infertility with impaired development of the testis. The incidence of these
      disorders has increased over the last few decades, and testicular cancer now
      affects 1% of the Danish and Norwegian male population. METHODS: To identify
      genetic variants that span the four TDS phenotypes, the authors performed a
      genome-wide association study (GWAS) using Affymetrix Human SNP Array 6.0 to
      screen 488 patients with symptoms of TDS and 439 selected controls with excellent
      reproductive health. Furthermore, they developed a novel integrative method that
      combines GWAS data with other TDS-relevant data types and identified additional
      TDS markers. The most significant findings were replicated in an independent
      cohort of 671 Nordic men. RESULTS: Markers located in the region of TGFBR3 and
      BMP7 showed association with all TDS phenotypes in both the discovery and
      replication cohorts. An immunohistochemistry investigation confirmed the presence
      of transforming growth factor beta receptor type III (TGFBR3) in peritubular and
      Leydig cells, in both fetal and adult testis. Single-nucleotide polymorphisms in
      the KITLG gene showed significant associations, but only with testicular cancer.
      CONCLUSIONS: The association of single-nucleotide polymorphisms in the TGFBR3 and
      BMP7 genes, which belong to the transforming growth factor beta signalling
      pathway, suggests a role for this pathway in the pathogenesis of TDS. Integrating
      data from multiple layers can highlight findings in GWAS that are biologically
      relevant despite having border significance at currently accepted statistical
      levels.

PMID- 22140274
TI  - HPAM: Hirshfeld Partitioned Atomic Multipoles.
AB  - An implementation of the Hirshfeld (HD) and Hirshfeld-Iterated (HD-I) atomic
      charge density partitioning schemes is described. Atomic charges and atomic
      multipoles are calculated from the HD and HD-I atomic charge densities for
      arbitrary atomic multipole rank l(max) on molecules of arbitrary shape and size.
      The HD and HD-I atomic charges/multipoles are tested by comparing molecular
      multipole moments and the electrostatic potential (ESP) surrounding a molecule
      with their reference ab initio values. In general, the HD-I atomic
      charges/multipoles are found to better reproduce ab initio electrostatic
      properties over HD atomic charges/multipoles. A systematic increase in precision
      for reproducing ab initio electrostatic properties is demonstrated by increasing
      the atomic multipole rank from l(max) = 0 (atomic charges) to l(max) = 4 (atomic
      hexadecapoles). Both HD and HD-I atomic multipoles up to rank l(max) are shown to
      exactly reproduce ab initio molecular multipole moments of rank L for L <=
      l(max). In addition, molecular dipole moments calculated by HD, HD-I, and ChelpG
      atomic charges only (l(max) = 0) are compared with reference ab initio values.
      Significant errors in reproducing ab initio molecular dipole moments are found if
      only HD or HD-I atomic charges used.

PMID- 22140275
TI  - A New Stress-Based Model of Political Extremism: Personal Exposure to Terrorism,
      Psychological Distress, and Exclusionist Political Attitudes.
AB  - Does exposure to terrorism lead to hostility toward minorities? Drawing on
      theories from clinical and social psychology, we propose a stress-based model of
      political extremism in which psychological distress-which is largely overlooked
      in political scholarship-and threat perceptions mediate the relationship between
      exposure to terrorism and attitudes toward minorities. To test the model, a
      representative sample of 469 Israeli Jewish respondents was interviewed on three
      occasions at six-month intervals. Structural Equation Modeling indicated that
      exposure to terrorism predicted psychological distress (t1), which predicted
      perceived threat from Palestinian citizens of Israel (t2), which, in turn,
      predicted exclusionist attitudes toward Palestinian citizens of Israel (t3).
      These findings provide solid evidence and a mechanism for the hypothesis that
      terrorism introduces nondemocratic attitudes threatening minority rights. It
      suggests that psychological distress plays an important role in political
      decision making and should be incorporated in models drawing upon political
      psychology.

PMID- 22140276
TI  - CJDATS Co-Occurring Disorders Screening Instrument for Mental Disorders (CODSI
      MD): A Pilot Study.
AB  - This article describes the development of an instrument to screen male and female
      offenders for co-occurring substance use and mental disorders. This phase
      developed and pilot tested (N = 100) the Criminal Justice Drug Abuse Treatment
      Studies (CJDATS) Co-occurring Disorders Screening Instrument for Mental Disorders
      (CODSI-MD), a 6-item instrument derived from three standard mental health
      screeners. The overall accuracy of the CODSI-MD (81%) compared favorably with the
      three standard instruments. A second 3-item instrument, developed to screen for
      severe mental disorders (the CODSI-SMD), had an overall accuracy of 82%. The
      results of this pilot study must be viewed cautiously, pending validation of the
      findings with a larger sample.

PMID- 22140277
TI  - Mapping the local reaction kinetics by PEEM: CO oxidation on individual (100)
      type grains of Pt foil.
AB  - The locally-resolved reaction kinetics of CO oxidation on individual (100)-type
      grains of a polycrystalline Pt foil was monitored in situ using photoemission
      electron microscopy (PEEM). Reaction-induced surface morphology changes were
      studied by optical differential interference contrast microscopy and atomic force
      microscopy (AFM). Regions of high catalytic activity, low activity and
      bistability in a (p,T)-parameter space were determined, allowing to establish a
      local kinetic phase diagram for CO oxidation on (100) facets of Pt foil. PEEM
      observations of the reaction front propagation on Pt(100) domains reveal a high
      degree of propagation anisotropy both for oxygen and CO fronts on the apparently
      isotropic Pt(100) surface. The anisotropy vanishes for oxygen fronts at
      temperatures above 465 K, but is maintained for CO fronts at all temperatures
      studied, i.e. in the range of 417 to 513 K. A change in the front propagation
      mechanism is proposed to explain the observed effects.

PMID- 22140278
TI  - Concise route to defined stereoisomers of the hydroxy acid of the chondramides.
AB  - The use of Kobayashi vinylogous aldol reaction in the reaction with acetaldehyde
      led to anti-aldol product 11. After reductive removal of the chiral auxiliary,
      the primary alcohol was converted to the allyliodide 14. This compound could be
      engaged in an Evans alkylation reaction, leading eventually to hydroxy acid 19.
      Inclusion of a Mitsunobu inversion reaction on the sequence starting with ent-11
      led to hydroxy ester 30, featuring a 6,7-syn-configuration. These hydroxy acids
      should help to elucidate the correct stereostructure of the chondramide
      depsipeptides.

PMID- 22140279
TI  - Notoamide E: Biosynthetic incorporation into notoamides C and D in cultures of
      Aspergillus versicolor NRRL 35600.
AB  - Notoamide E, a short-lived secondary metabolite, has been proposed as a
      biosynthetic intermediate to several advanced metabolites isolated from
      Aspergillus versicolor. In order to verify the role of this indole alkaloid along
      the biosynthetic pathway, synthetic doubly (13)C-labeled notoamide E was fed to
      Aspergillus versicolor. Analysis of the metabolites showed significant
      incorporation of notoamide E into the natural products notoamides C and D.

PMID- 22140280
TI  - Total syntheses of isonaamine C and isonaamidine E.
AB  - The total syntheses of two alkaloids isolated from a marine sponge of the
      Leucetta sp. have been accomplished in 6 and 7 steps starting from a 4,5
      diiodoimidazole derivative. Grignard mediated halogen-metal exchange was used to
      install the benzyl side chain. C2 substitution was accomplished via lithiation
      followed by quenching with trisyl azide which provided isonaamine C after
      hydrogenation. Isonaamidine E was then prepared from isonaamine C via
      introduction of the hydantoin ring by reaction with an activated parabanic acid.

PMID- 22140282
TI  - Contribution of honeybee drones of different age to colonial thermoregulation.
AB  - In addition to honeybee workers, drones also contribute to colonial
      thermoregulation. We show the drones' contribution to thermoregulation at 5
      different experimental temperatures ranging from 15-34  degrees C. The frequency
      and the degree of endothermy depended on the drones' local ambient temperature
      and age. Location on brood or non-brood areas had no influence. The frequency of
      endothermic drones and the intensity of endothermy increased with decreasing
      temperature. 30% of drones of 8 days and older heated their thorax by more than 1
      degrees C above the abdomen. The youngest drones (0-2 days) did not exceed this
      level of endothermy. Though young drones were less often engaged in active heat
      production, their contribution to brood warming was not insignificant because
      their abundance on the brood nest was 3.5 times higher than that of the oldest
      drones (>=13 days). Results suggest that the stimulus for the drones' increased
      frequency of heating at low experimental temperatures was their low local ambient
      air and/or comb temperature.

PMID- 22140281
TI  - Study on the biosynthesis of the notoamides: Pinacol-type rearrangement of the
      isoprenyl unit in deoxybrevianamide E and 6-hydroxydeoxybrevianamide E.
AB  - Two reverse-prenylated indole alkaloids, deoxybrevianamide E and 6
      hydroxydeoxybrevianamide E, are proposed as biosynthetic precursors for advanced
      metabolites isolated from the marine-derived Aspergillus sp. In order to uncover
      the role of the alkaloids in the biosynthetic pathway, the feeding experiments of
      the [(13)C](2)-[(15)N]-labeled deoxybrevianamide E and 6-hydroxydeoxybrevianamide
      E were performed to afford the metabolites, which were produced by oxidation and
      successive pinacol-type rearrangement of the isoprenyl units.

PMID- 22140283
TI  - Genome Size and Species Diversification.
AB  - Theoretically, there are reasons to believe that large genome size should favour
      speciation. Several major factors contributing to genome size, such as
      duplications and transposable element activity have been proposed to facilitate
      the formation of new species. However, it is also possible that small genome size
      promotes speciation. For example, selection for genome reduction may be resolved
      in different ways in incipient species, leading to incompatibilities. Mutations
      and chromosomal rearrangements may also be more stably inherited in smaller
      genomes. Here I review the following lines of empirical evidence bearing on this
      question: (i) Correlations between genome size and species richness of taxa are
      often negative. (ii) Fossil evidence in lungfish shows that the accumulation of
      DNA in the genomes of this group coincided with a reduction in species diversity.
      (iii) Estimates of speciation interval in mammals correlate positively with
      genome size. (iv) Genome reductions are inferred at the base of particular
      species radiations and genome expansions at the base of others. (v) Insect clades
      that have been increasing in diversity up to the present have smaller genomes
      than clades that have remained stable or have decreased in diversity. The general
      pattern emerging from these observations is that higher diversification rates are
      generally found in small-genome taxa. Since diversification rates are the net
      effect of speciation and extinction, large genomes may thus either constrain
      speciation rate, increase extinction rate, or both. I argue that some of the
      cited examples are unlikely to be explained by extinction alone.

PMID- 22140284
TI  - The most acidified Austrian lake in comparison to a neutralized mining lake.
AB  - This study investigated two mining lakes located in the north of Lower Austria.
      These lakes arose 45 years ago when open cast lignite mining ceased. The lakes
      are separated by a 7-m wide dam. Due to the oxidation of pyrite, both lakes have
      been acidified and exhibit iron, sulphate, and heavy metal concentrations several
      orders of magnitude higher than in circumneutral lakes. The water column of both
      lakes is divided into two layers by a pronounced chemocline. The smaller mining
      lake (AML), with pH close to of 2.6, is the most acidic lake in Austria, whereas
      flooding with stream water and by drainage from the surrounding fields
      neutralized the adjacent larger pit lake. The goal of our study was to
      investigate the effect of flooding on its physical, chemical and biological
      properties, in comparison to the pristine AML. Even relative to other extremely
      acidic lakes, the flora and fauna in the AML was reduced and composed of only two
      flagellate, one ciliate, and one rotifer species. The simplified pelagic food web
      in the mixolimnion consisted of heterotrophic bacteria, the mixotrophic
      flagellates Chlamydomonas acidophila and Ochromonas sp., the ciliate Oxytricha
      sp., and the rotifer Cephalodella sp. The latter two are as yet undescribed new
      species. The heliozoan Actinophrys sp. that may act as top predator occurred only
      in low abundance. The euglenid Lepocinclis buetschlii formed a stable deep
      chlorophyll maximum (DCM) at 7 m depth. Highest cell numbers of L. buetschlii in
      the DCM exceeded 10(8) L(-1). The neutralized mining lake harboured higher
      plankton diversity similar to that of natural circumneutral lakes. A peak of at
      least 16 different phytoplankton taxa was observed during summer. The zooplankton
      consisted of several copepod species, daphnids and other cladocerans, and at
      least six different rotifer species. Several fish species occurred in the
      neutralized lake. Although the effect of non-permanent flooding was largely
      sustainable, interannual fluctuations of the pH affected the plankton community
      and reduced its species diversity.

PMID- 22140286
TI  - Authoritarianism, perceived threat and exclusionism on the eve of the
      Disengagement: Evidence from Gaza.
AB  - Major political events such as terrorist attacks and forced relocation of
      citizens may have an immediate effect on attitudes towards ethnic minorities
      associated with these events. The psychological process that leads to political
      exclusionism of minority groups was examined using a field study among Israeli
      settlers in Gaza days prior to the Disengagement Plan adopted by the Israeli
      government on June 6, 2004 and enacted in August 2005. Lending credence to
      integrated threat theory and to theory on authoritarianism, our analyses show
      that the positive effect of religiosity on political exclusionism results from
      the two-staged mediation of authoritarianism and perceived threat. We conclude
      that religiosity fosters authoritarianism, which in turn tends to move people
      towards exclusionism both directly and through the mediation of perceived threat.

PMID- 22140285
TI  - Semi-synthesis of chondroitin sulfate-E from chondroitin sulfate-A.
AB  - Chondroitin sulfate-E (chondroitin-4, 6-disulfate) was prepared from chondroitin
      sulfate-A (chondroitin-4 - sulfate) by regioselective sulfonation, performed
      using trimethylamine sulfur trioxide in formamide under argon. The structure of
      semi-synthetic chondroitin sulfate-E was analyzed by PAGE, (1)H NMR, (13)C NMR,
      2D NMR and disaccharide analysis and compared with natural chondroitin sulfate-E.
      Both semi-synthetic and natural chondroitin sulfate-E were each biotinylated and
      immobilized on BIAcore SA biochips and their interactions with fibroblast growth
      factors displayed very similar binding kinetics and binding affinities. The
      current semi-synthesis offers an economical approach for the preparation of the
      rare chondroitin sulfate-E from the readily available chondroitin sulfate-A.

PMID- 22140287
TI  - Positive Affect Stimulation and Sustainment (PASS) Module for Depressed Mood: A
      preliminary investigation of treatment-related effects.
AB  - Positive affective functioning (PAF) is critical to the development, course and
      treatment of depressive symptoms. Targeting key features of PAF during treatment
      may provide a new angle through which to improve affective functioning and reduce
      symptoms. The current study was a treatment development trial for the Positive
      Affect Stimulation and Sustainment (PASS) Module. PASS is conceptualized as a
      means of capitalizing on positive events (e.g. planned through behavioral
      activation) by enhancing and sustaining positive affective states through
      savoring, and establishing positive attributions and expectancies. Participants
      were 27 female college students with dysphoric symptoms. There was a moderate
      effect of PASS on depressive symptoms. There was also a significant within
      session increase in positive affect from pre to post session among the PASS
      group, relative to active control; and a significant decrease in positive affect
      from pre (baseline) to post (follow-up) treatment among the control group,
      relative to PASS. Results provide preliminary evidence for the efficacy of the
      treatment module among young adults with depressed mood, and lay the foundation
      for future research.

PMID- 22140288
TI  - Fast and Accurate Approximation to Significance Tests in Genome-Wide Association
      Studies.
AB  - Genome-wide association studies commonly involve simultaneous tests of millions
      of single nucleotide polymorphisms (SNP) for disease association. The SNPs in
      nearby genomic regions, however, are often highly correlated due to linkage
      disequilibrium (LD, a genetic term for correlation). Simple Bonferonni correction
      for multiple comparisons is therefore too conservative. Permutation tests, which
      are often employed in practice, are both computationally expensive for genome
      wide studies and limited in their scopes. We present an accurate and
      computationally efficient method, based on Poisson de-clumping heuristics, for
      approximating genome-wide significance of SNP associations. Compared with
      permutation tests and other multiple comparison adjustment approaches, our method
      computes the most accurate and robust p-value adjustments for millions of
      correlated comparisons within seconds. We demonstrate analytically that the
      accuracy and the efficiency of our method are nearly independent of the sample
      size, the number of SNPs, and the scale of p-values to be adjusted. In addition,
      our method can be easily adopted to estimate false discovery rate. When applied
      to genome-wide SNP datasets, we observed highly variable p-value adjustment
      results evaluated from different genomic regions. The variation in adjustments
      along the genome, however, are well conserved between the European and the
      African populations. The p-value adjustments are significantly correlated with LD
      among SNPs, recombination rates, and SNP densities. Given the large variability
      of sequence features in the genome, we further discuss a novel approach of using
      SNP-specific (local) thresholds to detect genome-wide significant associations.
      This article has supplementary material online.

PMID- 22140289
TI  - THIS IS MY BABY: FOSTER PARENTS' FEELINGS OF COMMITMENT AND DISPLAYS OF DELIGHT.
AB  - This study examined the association between foster parents' commitment to their
      young foster children and the delight they showed in their interactions with
      children. Seventy foster parent-child dyads were included as participants. The
      dyads were videotaped during a play interaction when children were between 9 and
      28 months, with delight coded on the basis of foster parents' responses to
      children. Caregivers were interviewed with the "This Is My Baby" Interview (B.
      Bates & M. Dozier, 1998), with commitment coded as the extent to which parents
      expressed interest in enduring relationships with their foster children and the
      extent to which they thought of them as their own. Regression analyses revealed
      that commitment was a significant predictor of foster parent delight. Foster
      parents who were more highly committed to their foster children showed greater
      delight in their children than did foster parents who were less highly committed.
      These results suggest an important way in which caregiver commitment is
      transmitted to foster children.

PMID- 22140290
TI  - Penalized Fisher Discriminant Analysis and Its Application to Image-Based
      Morphometry.
AB  - Image-based morphometry is an important area of pattern recognition research,
      with numerous applications in science and technology (including biology and
      medicine). Fisher Linear Discriminant Analysis (FLDA) techniques are often
      employed to elucidate and visualize important information that discriminates
      between two or more populations. We demonstrate that the direct application of
      FLDA can lead to undesirable errors in characterizing such information and that
      the reason for such errors is not necessarily the ill conditioning in the
      resulting generalized eigenvalue problem, as usually assumed. We show that the
      regularized eigenvalue decomposition often used is related to solving a modified
      FLDA criterion that includes a least-squares-type representation penalty, and
      derive the relationship explicitly. We demonstrate the concepts by applying this
      modified technique to several problems in image-based morphometry, and build
      discriminant representative models for different data sets.

PMID- 22140291
TI  - Thermal Behaviour of Honeybees During Aggressive Interactions.
AB  - We report here on the interrelationship of aggressive behaviour and
      thermoregulation in honeybees. Body temperature measurements were carried out
      without behavioural disturbance by infrared thermography. Guard bees, foragers,
      drones, and queens involved in aggressive interactions were always endothermic,
      i.e. had their flight muscles activated. Guards made differential use of their
      endothermic capacity. Mean thorax temperature was 34.2-35.1 degrees C during
      examination of bees but higher during fights with wasps (37 degrees C) or attack
      of humans (38.6 degrees C). They usually cooled down when examining bees whereas
      examinees often heated up during prolonged interceptions (maximum >47 degrees C).
      Guards neither adjusted their thorax temperature (and thus flight muscle function
      and agility) to that of examined workers, nor to that of drones, which were 2-7
      degrees C warmer. Guards examined cool bees (<33 degrees C) longer than warmer
      ones, supporting the hypothesis that heating of examinees facilitates odour
      identification by guards, probably because of vapour pressure increase of
      semiochemicals with temperature. Guards in the core of aggressive balls clinged
      to the attacked insects to fix them and kill them by heat (maximum 46.5 degrees
      C). Bees in the outer cluster layers resembled normal guards behaviourally and
      thermally. They served as active core insulators by heating up to 43.9 degrees C.
      While balled wasps were cooler (maximum 42.5 degrees C) than clinging guards
      balled bees behaved like examinees with maximum temperatures of 46.6 degrees C,
      which further supports the hypothesis that the examinees heat up to facilitate
      odour identification.

PMID- 22140292
TI  - Relevance of attention in auditory sensory gating paradigms in schizophrenia A
      pilot study.
AB  - The paired-click paradigm (PCP) is widely used to study sensory habituation or
      gating in a number of psychiatric and neurological conditions. The classic
      paradigm does not control for attentional factors. In order to assess the
      influences of incorporating attentional control measures we administered the
      auditory PCP (S1-S2) in three different attention (passive, auditory attention to
      S2, visual attention to a concurrent continuous performance task [CPT])
      conditions to a group of chronic, medicated schizophrenia patients (N=12) and a
      group of healthy subjects (N=15) to evaluate the effects of attention on sensory
      gating measures. A significant effect of attention on S1 amplitudes was shown for
      P50 in both groups, and N100 or P200 in schizophrenia patients. Attention status
      had a significant effect on S2 amplitudes for N100 and P200, and N100 and P200
      gating ratios. Despite the effect of attention on S1 P50 amplitudes there was no
      effect on the gating ratio. In terms of group differences, visual attention to
      the concurrent CPT during the paired-click sensory gating task significantly
      enhanced the detection of deficient gating of the N100 and P200 components in
      schizophrenia patients. The data support the continued utilization of the passive
      gating paradigm for examining P50 gating but strongly suggest that for studies
      examining gating of the N100 or P200 components, a visual distraction paradigm
      may enhance the detection of abnormal gating in schizophrenia patients.

PMID- 22140293
TI  - Structurally Characterized Cationic Silver(I) and Ruthenium(II)carbene complexes
      of 1,2,3-Triazol-5-ylidenes.
AB  - A novel 1,3,4-substituted 1,2,3-triazolium salt was found to function as an
      effective precursor for the synthesis of the first structurally characterized
      cationic silver(I) and ruthenium(II)carbene complexes of overall 1:2 ligand-to
      metal stoichiometry. The Ag(I) complex crystallized in the form of an eight
      silver atom-containing cluster, whereas the Ru(II) complex proved to be a
      discrete species and was found to be capable of initiating the ring-opening
      metathesis polymerization of norbornene upon activation with
      (trimethylsilyl)diazomethane.

PMID- 22140294
TI  - Early Postnatal Ozone Exposure Alters Rat Nodose and Jugular Sensory Neuron
      Development.
AB  - Sensory neurons originating in nodose and jugular ganglia that innervate airway
      epithelium (airway neurons) play a role in inflammation observed following
      exposure to inhaled environmental irritants such as ozone (O(3)). Airway neurons
      can mediate airway inflammation through release of the neuropeptide substance P
      (SP). While susceptibility to airway irritants is increased in early life, the
      developmental dynamics of afferent airway neurons are not well characterized. The
      hypothesis of this study was that airway neuron number might increase with
      increasing age, and that an acute, early postnatal O(3) exposure might increase
      both the number of sensory airway neurons as well as the number SP-containing
      airway neurons. Studies using Fischer 344 rat pups were conducted to determine if
      age or acute O(3) exposure might alter airway neuron number. Airway neurons in
      nodose and jugular ganglia were retrogradely labeled, removed, dissociated, and
      counted by means of a novel technique employing flow cytometry. In Study 1,
      neuron counts were conducted on postnatal days (PD) 6, 10, 15, 21, and 28.
      Numbers of total and airway neurons increased significantly between PD6 and PD10,
      then generally stabilized. In Study 2, animals were exposed to O(3) (2 ppm) or
      filtered air (FA) on PD5 and neurons were counted on PD10, 15, 21, and 28. O(3)
      exposed animals displayed significantly less total neurons on PD21 than FA
      controls. This study shows that age-related changes in neuron number occur, and
      that an acute, early postnatal O(3) exposure significantly alters sensory neuron
      development.

PMID- 22140295
TI  - Body temperature of the parasitic wasp Pimpla turionellae (Hymenoptera) during
      host location by vibrational sounding.
AB  - The pupal parasitoid Pimpla turionellae (L.) uses self-produced vibrations
      transmitted on the plant substrate, so-called vibrational sounding, to locate
      immobile concealed pupal hosts. The wasps are able to use vibrational sounding
      reliably over a broad range of ambient temperatures and even show an increased
      signal frequency and intensity at low temperatures. The present study
      investigates how control of body temperature in the wasps by endothermic
      mechanisms may facilitate host location under changing thermal environments.
      Insect body temperature is measured with real-time IR thermography on plant-stem
      models at temperature treatments of 10, 18, 26 and 30  degrees C, whereas
      behaviour is recorded with respect to vibrational host location. The results
      reveal a low-level endothermy that likely interferes with vibrational sound
      production because it occurs only in nonsearching females. At the lowest
      temperature of 10  degrees C, the thoracic temperature is 1.15  degrees C warmer
      than the ambient surface temperature whereas, at the high temperatures of 26 and
      30  degrees  C, the wasps cool down their thorax by 0.29 and 0.47  degrees C,
      respectively, and their head by 0.45 and 0.61  degrees C below ambient surface
      temperature. By contrast, regardless of ambient temperature, searching females
      always have a slightly elevated body temperature of at most 0.30  degrees C above
      the ambient surface temperature. Behavioural observations indicate that searching
      females interrupt host location more frequently at suboptimal temperatures,
      presumably due to the requirements of thermoregulation. It is assumed that both
      mechanisms, producing vibrations for host location and low-level endothermy, are
      located in the thorax. Endothermy by thoracic muscle work probably disturbs
      signal structure of vibrational sounding, so the processes cannot be used at the
      same time.

PMID- 22140296
TI  - Some natural flavonoids are competitive inhibitors of Caspase-1, -3 and -7
      despite their cellular toxicity.
AB  - A common feature of both apoptosis and inflammation is the activation of
      caspases. Caspases are aspartate-directed cysteine proteases that have numerous
      cellular targets. It has been discovered that several flavonoids are inhibitors
      of caspases. Flavonoids are members of a family of polyphenolic compounds from
      plants that have many biological properties, one of which is the ability to
      induce cell death. Some flavonoids are selective inhibitors of particular
      caspases. Since some of the inhibitory flavonoids are nevertheless cytotoxic,
      these results suggest that flavonoid-induced cell death may be occurring through
      a non-classical apoptosis pathway that is not dependent on caspase activity.

PMID- 22140297
TI  - Contrasting Adult Literacy Learners With and Without Specific Learning
      Disabilities.
AB  - Contrasting adult literacy learners with and without specific learning
      disabilities This study of 311 adult education (AE) learners found 29% self
      reported having a specific learning disability (SLD). Significant differences in
      demographic, academic, and life experience variables between the adult learners
      with and without SLD included: prior participation in special education, having
      both an SLD diagnosis and a high school diploma, low reading scores, middle age,
      and negative perceptions about limitations due to reading abilities. A post-hoc
      regression analysis found SLD status significantly contributes to variance in
      reading level when controlling for age and IQ. From these findings we conclude
      that SLD status should be considered an educationally relevant variable in adult
      education that warrants a diagnostic or clinical teaching approach.

PMID- 22140298
TI  - Effect of lactation stage and concurrent pregnancy on milk composition in the
      bottlenose dolphin.
AB  - ALTHOUGH MANY TOOTHED WHALES (CETACEA: Odontoceti) lactate for 2-3 years or more,
      it is not known whether milk composition is affected by lactation stage in any
      odontocete species. We collected 64 pooled milk samples spanning 1-30 months
      postpartum from three captive bottlenose dolphins Tursiops truncatus. Milks were
      assayed for water, fat, crude protein (TN * 6.38) and sugar; gross energy was
      calculated. Ovulation and pregnancy were determined via monitoring of milk
      progesterone. Based on analysis of changes in milk composition for each
      individual dolphin, there were significant increases (P<0.05) in fat (in all
      three dolphins) and crude protein (in two of three), and a decrease (P<0.05) in
      water (in two of three) over the course of lactation, but the sugar content did
      not change. In all three animals, the energy content was positively correlated
      with month of lactation, but the percentage of energy provided by crude protein
      declined slightly but significantly (P<0.05). At mid-lactation (7-12 months
      postpartum, n=17), milk averaged 73.0+/-1.0% water, 12.8+/-1.0% fat, 8.9+/-0.5%
      crude protein, 1.0+/-0.1% sugar, 1.76+/-0.09 kcal g(-1) (=7.25 kJ g(-1)) and
      30.3+/-1.3% protein:energy per cent. This protein:energy per cent was
      surprisingly high compared with other cetaceans and in relation to the growth
      rates of calves. Milk progesterone indicated that dolphins ovulated and conceived
      between 413 and 673 days postpartum, following an increase in milk energy
      density. The significance of these observed compositional changes to calf
      nutrition will depend on the amounts of milk produced at different stages of
      lactation, and how milk composition and yield are influenced by sampling
      procedure, maternal diet and maternal condition, none of which are known.

PMID- 22140299
TI  - ASYMPTOTIC PROPERTIES OF SUFFICIENT DIMENSION REDUCTION WITH A DIVERGING NUMBER
      OF PREDICTORS.
AB  - We investigate asymptotic properties of a family of sufficient dimension
      reduction estimators when the number of predictors p diverges to infinity with
      the sample size. We adopt a general formulation of dimension reduction estimation
      through least squares regression of a set of transformations of the response.
      This formulation allows us to establish the consistency of reduction projection
      estimation. We then introduce the SCAD max penalty, along with a difference
      convex optimization algorithm, to achieve variable selection. We show that the
      penalized estimator selects all truly relevant predictors and excludes all
      irrelevant ones with probability approaching one, meanwhile it maintains
      consistent reduction basis estimation for relevant predictors. Our work differs
      from most model-based selection methods in that it does not require a traditional
      model, and it extends existing sufficient dimension reduction and model-free
      variable selection approaches from the fixed p scenario to a diverging p.

PMID- 22140300
TI  - Development of a novel polymeric fiber-optic magnetostrictive metal detector.
AB  - The purpose this paper is the development a novel polymeric fiber-optic
      magnetostrictive metal detector, using a fiber-optic Mach-Zehnder interferometer
      and polymeric magnetostrictive material. Metal detection is based on the strain
      induced optical path length change steming from the ferromagnetic material
      introduced in the magnetic field. Varied optical phase shifts resulted largely
      from different metal objects. In this paper, the preliminary results on the
      different metal material detection will be discussed.

PMID- 22140301
TI  - Maternal Depressive Symptoms When Caring for a Child with Mental Health Problems.
AB  - As primary caregivers of children with mental health problems, mothers face
      challenges that put them at risk for depression, which is rarely identified or
      addressed. The aims of this paper were to (a) identify mean differences among
      demographic, stressor, threat, and resource variables specified in a theoretical
      model and thought to be associated with maternal depressive symptoms and (b)
      determine how much variability in depressive symptoms is explained by these
      variables. High levels and prevalence of depressive symptoms were found within a
      quality of life study that these data were drawn from. Of 139 mothers
      participating in this study, 58% had a score of 16 or greater on the CES-D
      indicating moderate to high levels of depressive symptoms. Significant
      differences were found between mothers with higher versus lower levels of
      depressive symptoms for 11 of the 18 variables. Hierarchical regression was used
      to examine the variance explained in depressive symptoms based upon the
      conceptual model with 4 composite variables. Income (step 1), behavioral problems
      (step 2), threat appraisal (step 3), and resource appraisal (step 4) combined
      explained 42% of the variance.

PMID- 22140302
TI  - Religion and Substance Use among Youths of Mexican Heritage: A Social Capital
      Perspective.
AB  - Despite elevated levels of substance use among many Latino youths, there has been
      little research on protective factors against such use. In keeping with federal
      commitments to address health disparities, this prospective study examined the
      protective influence of religion on substance use among a school-based sample (N
      = 804) of youths of Mexican heritage in the American Southwest. Drawing from the
      social capital literature, the authors posited that both integration into
      religious networks and trust in religious values at time 1 (Tl) would predict
      less likelihood of using substances at time 2 (T2) but that exposure to religious
      norms at Tl would not predict subsequent substance use at T2. The hypotheses
      regarding religious networks and religious norms were largely confirmed, whereas
      little support emerged for the hypothesis regarding religious values. The results
      are discussed in light of the various pathways through which religion may exhibit
      a protective influence.

PMID- 22140303
TI  - NISO Z39.96The Journal Article Tag Suite (JATS): What Happened to the NLM DTDs?
AB  - The NLM DTDs were descendants of the pmc-1.dtd, which was written to support the
      PubMed Central project. The NLM DTDs have become NISO Z39.96 JATS: The Journal
      Article Tag Suite.

PMID- 22140304
TI  - Choroidal findings in idiopathic uveal effusion syndrome.
AB  - PURPOSE: We report choroidal findings by means of enhanced depth imaging spectral
      domain optical coherence tomography (EDI-OCT) in a patient with idiopathic uveal
      effusion syndrome (IUES). CASE REPORT: A 41-year-old man was referred to us with
      ciliochoroidal and non-rhegmatogenous retinal detachments. Sclerectomies and
      sclerostomies were performed at the equator in the lower quadrants, resulting in
      resolution of the ciliochoroidal and retinal detachments. EDI-OCT demonstrated
      low-reflective areas in the outer choroid. The subfoveal choroidal thickness
      measured vertically from the outer border of the RPE to the inner border of the
      sclera was 787 MUm which was significantly thicker than the normal value (272 +/-
      90 MUm, n = 131) obtained from age-matched normal controls. CONCLUSIONS: The
      findings made by EDI-OCT have provided additional evidence that choroidal
      alterations play a role in the pathological process in IUES.

PMID- 22140305
TI  - Orbital apex syndrome associated with herpes zoster ophthalmicus.
AB  - We report our findings for a patient with orbital apex syndrome associated with
      herpes zoster ophthalmicus. Our patient was initially admitted to a neighborhood
      hospital because of nausea and loss of appetite of 10 days' duration. The day
      after hospitalization, she developed skin vesicles along the first division of
      the trigeminal nerve, with severe lid swelling and conjunctival injection. On
      suspicion of meningoencephalitis caused by varicella zoster virus, antiviral
      therapy with vidarabine and betamethasone was started. Seventeen days later,
      complete ptosis and ophthalmoplegia developed in the right eye. The light reflex
      in the right eye was absent and anisocoria was present, with the right pupil
      larger than the left. Fat-suppressed enhanced T1-weighted magnetic resonance
      images showed high intensity areas in the muscle cone, cavernous sinus, and
      orbital optic nerve sheath. Our patient was diagnosed with orbital apex syndrome,
      and because of skin vesicles in the first division of the trigeminal nerve, the
      orbital apex syndrome was considered to be caused by herpes zoster ophthalmicus.
      After the patient was transferred to our hospital, prednisolone 60 mg and
      vidarabine antiviral therapy was started, and fever and headaches disappeared
      five days later. The ophthalmoplegia and optic neuritis, but not the anisocoria,
      gradually resolved during tapering of oral therapy. From the clinical findings
      and course, the cause of the orbital apex syndrome was most likely invasion of
      the orbital apex and cavernous sinus by the herpes virus through the trigeminal
      nerve ganglia.

PMID- 22140306
TI  - Surgically induced necrotizing scleritis after primary pterygium surgery with
      conjunctival autograft.
AB  - BACKGROUND: Although pterygium excision with conjunctival autograft is a widely
      performed surgical procedure, surgically induced necrotizing scleritis (SINS)
      following such surgery is extremely rare. METHODS: A 68-year-old man underwent
      nasal pterygium excision with conjunctival autograft uneventfully. On
      postoperative day 17, the conjunctival graft was avascular, with epithelial
      defect. Although topical steroid and antibacterial treatments were continued, the
      graft and sclera melted, with the ischemic sclera showing gradual thinning. The
      thinning area spread to the adjoining cornea, and active inflammation with
      epithelial defect was observed adjacent to the site of thinning. RESULTS:
      Systemic and microbiological examination was noncontributory. The patient was
      suspected of having SINS, and administration of oral prednisolone was started.
      Although the necrotic area was reduced temporarily, medication was discontinued
      due to nausea, and the area of thinning increased. Conjunctival flap surgery was
      later performed, and the graft was well accepted. CONCLUSIONS: SINS must be
      considered in the differential diagnosis of patients with scleritis following
      pterygium surgery, especially if radiation or mitomycin C has not been used.

PMID- 22140307
TI  - Dexamethasone intravitreal implant for the treatment of noninfectious uveitis.
AB  - Uveitis can be a sight-threatening eye disease with significant morbidity.
      Corticosteroids remain the mainstay of treatment of uveitis and provide an
      effective treatment against ocular inflammation. However, the various modes
      available for corticosteroid drug delivery can carry significant ocular and
      systemic side effects which can limit their use in the treatment of uveitis. In
      an effort to avoid the damage to ocular structures that can ensue with recurrent
      episodes of ocular inflammation, the side effects associated with systemic
      steroids, and the need for repeated administration of both topical and locally
      injected corticosteroids, sustained-release intraocular corticosteroid implants
      have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex((r));
      Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant
      has been shown to be effective in the treatment of macular edema and
      noninfectious posterior uveitis and has been approved by the FDA for these
      entities. This review will highlight the current methods available for
      corticosteroid delivery to the eye with a particular emphasis on the DEX
      intravitreal implant and the evidence currently available for its use in
      noninfectious uveitis.

PMID- 22140309
TI  - Intracorneal ring implantation using Intralase(r) with partial coverage of the
      cone in a patient after an alkaline injury.
AB  - PURPOSE: To report the use of intracorneal ring segment (ICRS) implantation in a
      case of severe corneal thinning and irregularity secondary to alkali burn. CASE
      REPORT: A 33-year-old man who had a history of ocular alkali burn in the right
      eye was admitted. His best corrected visual acuity was 0.16 with manifest
      refraction of +5.00 (-7.00 * 180 degrees ). Orbscan II((r)) revealed steepening
      of >53 D superiorly, excessive thinning inferiorly with thinnest pachymetric
      reading of 269 MUm. Two KeraRing((r)) segments, 200 MUm thick and 90 degrees 
      arced, were implanted. During intrastromal channel creation by Intralase((r)),
      the inferior half of the applanating cone was covered by a gelatinous paper to
      prevent the penetration of the laser beam into the anterior chamber. In the first
      year postoperation, best corrected visual acuity was 0.7 with manifest refraction
      of +1.50 (-3.50 * 35 degrees ). Visante((r)) opticial coherence tomography
      displayed ICRS at a depth of <370 MUm. CONCLUSION: ICRS implantation with this
      novel approach may be an option in eyes with severe corneal irregularity and
      thinning.

PMID- 22140308
TI  - Effect of caffeine on the intraocular pressure in patients with primary open
      angle glaucoma.
AB  - PURPOSE: Coffee and tea are very common nonalcoholic beverages. However, their
      intake, particularly that of coffee, has been suggested to increase intraocular
      pressure (IOP) in patients with open angle glaucoma/ocular hypertension. The
      causative agent has been suggested to be their caffeine content. The objective of
      this study was to determine if this represents a direct caffeine effect. This
      study was therefore done using pure caffeine applied directly to the eyes.
      METHODS: The study was conducted with five human volunteers with open angle
      glaucoma/ ocular hypertension. IOP was measured using a Perkins applanation
      tonometer. Eye drops of 1% caffeine were prepared in-home. Following the initial
      (basal) measurement of the IOP, 50 MUL of the eye drop preparation was instilled
      in the eye at 0-, 4-, and 6-hour intervals. IOPs were measured 30 minutes after
      each instillation. A second study was also undertaken following the first. In
      this study, the same patients instilled the eye drops three times per day for 1
      week at home and then returned to the clinic on day 7. They were then again
      treated with caffeine eye drops as above and IOPs measured. RESULTS: In the 1-day
      study, the mean basal IOP was 23.6 +/- 2.80 mmHg. Thirty minutes after
      instillation of the drops as described, the pressures were 23.2 +/- 1.93, 22.2 +/
      1.99, and 22.6 +/- 2.31. The basal reading was taken at 10 am and another
      reading was then taken at 10.30 am. Additional eye drops were instilled at 2 and
      8 pm and readings taken 30 minutes after each instillation. In the 1 week study,
      the basal value was 22.6 +/- 2.32. After instillation of the drops as above the
      values were 23 +/- 2.16, 22.4 +/- 2.27, and 23 +/- 1.94. CONCLUSION:
      Administration of caffeine into the eyes of patients did not have any effect on
      IOP and it remained relatively unchanged. This was true in the 1-day study as
      well as in the 1-week study. A cumulative effect was not visible. The results
      therefore demonstrate that caffeine has no significant effect on IOP in patients
      with glaucoma. Any effects reported in coffee drinkers may therefore be related
      to other constituents in coffee, known to be generated pyrolytically from
      endogenous constituents of coffee beans by roasting at relatively high
      temperature, combined with the osmotic effects imposed by adequate fluid intake,
      known to be common in glaucoma patients.

PMID- 22140310
TI  - Early imaging of a macular hole following vitrectomy with primary silicone oil
      tamponade.
AB  - BACKGROUND: To describe the morphology of a macular hole in the early
      postoperative period following vitrectomy with primary silicone oil tamponade.
      METHODS: A case report with optical coherence tomography (OCT) scans prior to
      surgery, at 20 minutes postoperatively and then at 17 hours postoperatively.
      RESULTS: OCT images of a 73-year-old woman with a stage 3 macular hole were
      obtained. At 20 minutes postoperatively, there was a reduction in intraretinal
      cysts and a reduction in macular hole size with elevated-open configuration. At
      17 hours postoperatively, complete macular hole closure was noted. CONCLUSION:
      OCT Images of a macular hole in the early postoperative period have been
      successfully obtained. Macular holes can close within 24 hours postoperatively
      and show morphological changes that may be predictive of closure within 20
      minutes postoperatively.

PMID- 22140311
TI  - Nonselective beta-blocker propranolol for orbital and periorbital hemangiomas in
      infants: a new first-line of treatment?
AB  - PURPOSE: To determine the effectiveness and possible side effects of using
      propranolol for the treatment of orbital and periorbital infantile hemangiomas.
      METHODS: Infants with periorbital or orbital hemangiomas who had not received
      either local or systemic corticosteroids were recruited. The changes in tumor
      size, color, and texture, and any side effects of the drug were recorded.
      RESULTS: Fifteen infants with a mean age of 8.13 +/- 4.7 months were treated
      according to the set protocol. A change in the color and texture of the
      hemangioma occurred in the first week following treatment. Mean duration of
      treatment was 7.67 +/- 3.96 months. The size of hemangiomas decreased from a mean
      of 2.4 +/- 0.9 cm to a mean of 1.6 +/- 1.0 cm 3 months after treatment (P =
      0.001). One patient had to stop the drug because of peripheral vascular ischemia.
      Another case had the dose reduced to control a mild hyperglycemia. Serious side
      effects were not observed. A single case of tumor regrowth (8.3%) was recorded.
      CONCLUSION: Treatment of 1-2 mg/kg/day propranolol proved to be effective and
      associated with minimal side effects. It is likely to replace steroids as the
      first-line of treatment of hemangiomas in infants.

PMID- 22140312
TI  - Application of the AJCC 7th edition carcinoma of the eyelid staging system: a
      medical center pathology based, 15-year review.
AB  - CONTEXT: The purpose of this study was to conduct a quality improvement (QI),
      applied practical review of the American Joint Committee on Cancer (AJCC) 7th
      edition, Carcinoma of the Eyelid staging system. AJCC utilizes a primary tumor,
      lymph node, metastasis (pTNM) cancer staging approach. OBJECTIVE: We wanted to
      determine if the AJCC pTNM carcinoma staging system identified patients with
      highly aggressive carcinoma of the eyelid. We also wanted to determine if there
      were any unexpected issues in its practical application. DESIGN: We conducted a
      15-year, consecutive, retrospective review of all cases of excisional biopsy for
      carcinoma of the eyelid. We reviewed the original histopathology slides and
      complete pathology records for each case. RESULTS: Over a 15-year review period,
      52 cases of excisional biopsy for carcinoma of the eyelid were identified. The
      average age of the study population was 72 years. Nodular well-differentiated
      basal cell carcinoma (BCC) was the predominant histology for 85% of cases.
      Morpheaform/metatypical BCC was the next dominant at 9%. Squamous cell carcinoma
      and sebaceous carcinoma followed at 4% and 2%, respectively. We were able to
      assign clear staging to 50 of the 52 cases with the available pathology data. The
      stage results were as follows: stage 1A 72%, stage 1B 22%, stage II 4%, stage III
      2%, with no cases of stage IV metastatic disease. CONCLUSIONS: The 7th edition
      AJCC Carcinoma of the Eyelid chapter proved to be a practical tool for carcinoma
      staging of the eyelid. The largest tumor dimension remains an effective
      predictive factor. High-grade pathologic prognostic factors such as tumor
      necrosis or perineural spread had a 100% association with a final stage of II or
      greater. Concordance and compliance was 100% for the recommended site-specific
      pathologic risk factors. Regarding squamous cell carcinoma of the eyelid, three
      new required data points had a 0% reporting rate over 15 years. Overall, smaller
      less invasive tumors were classified as stage 1A and 1B tumors. More invasive and
      higher risk tumors fell into appropriate higher staging classifications. The
      newly recommended prognostic site-specific tumor factors appear to work well with
      a high concordance with staging severity, and strong medical community
      acceptance.

PMID- 22140313
TI  - Current state of cardiac rehabilitation in Germany: patient characteristics, risk
      factor management and control status, by education level.
AB  - BACKGROUND: After the acute hospital stay, most cardiac patients in Germany are
      transferred for a 3-4-week period of inpatient cardiac rehabilitation. We aim to
      describe patient characteristics and risk factor management of cardiac
      rehabilitation patients with a focus on drug treatment and control status,
      differentiated by education level (low level, elementary school; intermediate
      level, secondary modern school; high level, grammar school/university). METHODS:
      Data covering a time period between 2003 and 2008 from 68,191 hospitalized
      patients in cardiac rehabilitation from a large-scale registry (Transparency
      Registry to Objectify Guideline- Oriented Risk Factor Management) were analyzed
      descriptively. Further, a multivariate model was applied to assess factors
      associated with good control of risk factors. RESULTS: In the total cohort,
      patients with a manifestation of coronary artery disease (mean age 63.7 years,
      males 71.7%) were referred to cardiac rehabilitation after having received
      percutaneous coronary intervention (51.6%) or coronary bypass surgery (39.5%).
      Statin therapy increased from 76.3% at entry to 88.9% at discharge, and low
      density lipoprotein cholesterol < 100 mg/dL rates increased from 31.1% to 69.6%.
      Mean fasting blood glucose decreased from 108 mg/dL to 104 mg/dL, and mean
      exercise capacity increased from 78 W to 95 W. Age and gender did not differ by
      education. In contrast with patients having high education, those with low
      education had more diabetes, hypertension, and peripheral arterial disease, had
      lower exercise capacity, and received less treatment with statins and guideline
      orientated therapy in general. In the multivariate model, good control was
      significantly more likely in men (odds ratio 1.38; 95% confidence interval 1.30
      1.46), less likely in patients of higher age (0.99; 0.99-0.99), with diabetes
      (0.90; 0.85-0.95), or peripheral arterial disease (0.88; 0.82-0.95). Compared
      with a low level education, a mid level education was associated with poor
      control (0.94; 0.89-0.99), while high education did not have a significant effect
      (1.08; 0.99-1.17). CONCLUSION: Patients with different levels of education
      treated in cardiac rehabilitation did not differ relevantly in terms of
      demographics, but did differ in some clinical aspects. With respect to the
      ultimate goal of cardiac rehabilitation, ie, optimal control of risk factors,
      education level does not play an important role.

PMID- 22140314
TI  - Central aortic blood pressure, augmentation index, and reflected wave transit
      time: reproducibility and repeatability of data obtained by oscillometry.
AB  - BACKGROUND: The evidence suggests that arterial stiffness acts as an independent
      predictor of general as well as cardiovascular mortality, strokes in patients
      with arterial hypertension, type 2 diabetes mellitus in the elderly, and in the
      general population. The oscillometric method measures parameters of arterial
      stiffness by applying special methods of processing oscillograms. This is a study
      of the reproducibility and repeatability of central aortic systolic blood
      pressure (SBP), augmentation index, and reflected wave transit time measured by
      Vasotens((r)) technology. METHODS: Anthropometric and hemodynamic measurements
      for 90 volunteers were made by two observers using the 24-hour blood pressure
      monitoring system, BPLab((r)), with Vasotens technology in "office" mode, over a
      period of two days and always at the same time in the morning. Initialization of
      the device was performed prior to each measurement cycle for each participant.
      RESULTS: Analysis of short-term repeatability and reproducibility data for
      central aortic systolic blood pressure, reflected wave transit time, and
      augmentation index did not reveal any statistically significant differences. For
      observer A, SBP was 0.11 +/- 7.53 mmHg and aortic SBP was 0.26 +/- 6.11 mmHg; for
      observer B, SBP was 0.14 +/- 8.42 and aortic SBP was 0.2 +/- 7.25 mmHg. Short
      term reproducibility for the different observers with averaging of both
      measurements was 0.36 +/- 5.69 mmHg for SBP and 0.37 +/- 6.7 mmHg for aortic SBP;
      the next day, repeatability for observer A was 0.52 +/- 10.7 mmHg for SBP and
      0.73 +/- 8.98 mmHg for aortic SBP. CONCLUSION: BPLab with Vasotens technology has
      good reproducibility and repeatability, and can be recommended for clinical
      vascular risk estimation.

PMID- 22140315
TI  - Aneurysm of the tibial-saphenous fistula in hemodialysis patient: the results of
      surgical treatment.
AB  - Arteriovenous fistulas are widely used for hemodialysis patients with end-stage
      renal failure. Due to the lack of suitable veins because of the arteriovenous
      fistulas previously opened in the upper extremity, alternative access routes are
      being tested. Few complications of long-term alternative arteriovenous fistulas
      have been reported in the literature. We report the results of surgical repairs
      of aneurysms that occurred on anterior tibial-saphenous arteriovenous fistulas
      (along the vein) in patients with end-stage renal disease after 5 years on
      hemodialysis.

PMID- 22140316
TI  - Evaluation of carotid intima-media thickness and flow-mediated dilatation in
      middle-aged patients with nonalcoholic fatty liver disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in the
      general population and is the most common liver disease in Western countries. It
      is a feature of metabolic syndrome and is characterized by excessive accumulation
      of fat in the liver cells. METHODS: We examined 84 consecutive middle-aged (under
      45 years) patients with NAFLD and 65 control subjects matched for age, gender,
      and body mass index to determine carotid intima-media thickness (CIMT) and flow
      mediated dilatation (FMD) in the brachial artery. RESULTS: There was a
      statistically significant difference between CIMT and percentage increase in FMD
      in the patient group (P = 0.002; r = 0.33) when compared with the control group
      (P = 0.97; r = 0.005). The mean +/- standard deviation CMIT was 0.65 +/- 0.09 mm
      in patients and 0.55 +/- 0.07 mm in controls. This difference was statistically
      significant (P = 0.001). Mean FMD in patients was 6.4% and 15.7% in controls.
      This difference was statistically significant (P = 0.001). CONCLUSION: This study
      shows that pure NAFLD without metabolic syndrome in middle-aged subjects is
      strongly associated with morphological (CIMT) and physiological (FMD) changes.
      These findings may have an important role in increasing cardiovascular risk in
      these patients.

PMID- 22140317
TI  - Hemorrhagic infarction at 33 days after birth in a healthy full-term neonate.
AB  - Intraparenchymal hemorrhage in the full-term neonate rarely occurs more than 2
      weeks after birth, and its definitive cause remains unclear. In the present
      report, a case of a patient with intraparenchymal hemorrhage occurring 33 days
      after birth is described. Histological examination of the brain tissue obtained
      during hematoma evacuation through craniotomy showed hemorrhagic infarction.
      Patent foramen ovale may have been present and this may have led to spontaneous
      paradoxical cerebral embolism followed by hemorrhagic infarction.

PMID- 22140318
TI  - Vitamin D status and peripheral arterial disease: evidence so far.
AB  - BACKGROUND: Vitamin D deficiency has recently been implicated as a contributory
      factor in the development of peripheral arterial disease (PAD). METHODS: A review
      of the published literature on PAD and vitamin D was undertaken using Medline,
      PubMed, and Embase, and cross-referenced. All relevant published papers on the
      subject were reviewed. RESULTS: Published studies have shown that there is a
      significant association between vitamin D and PAD. Populations with lower vitamin
      D levels are more likely to develop PAD in a graded manner. Higher amputation
      rates are also observed among patients with PAD and lower vitamin D levels. In
      addition, vitamin D deficiency is significantly associated with increased risk of
      cardiovascular adverse events. This was also observed in the mouse model where
      low vitamin D led to the development of atherosclerosis. CONCLUSION: This study
      shows that vitamin D deficiency could be an independent risk factor for the
      development of PAD and that this risk factor is easily correctable. Further
      studies should look into the effects of vitamin D supplementation in patients
      with PAD.

PMID- 22140319
TI  - Telmisartan and cardioprotection.
AB  - Cardiovascular risk reduction has been the target of several large clinical
      trials in the last decade. As the activation of the renin-angiotensin-aldosterone
      system (RAAS) plays a central role in the pathogenesis of atherosclerosis and
      cardiovascular disease, RAAS blockade has been suggested to be among the most
      efficient cardioprotective interventions, as revealed with the angiotensin
      converting enzyme (ACE) inhibitors trials. The angiotensin receptor blockers'
      (ARBs) efficacy in lowering blood pressure has been very well established.
      Telmisartan is however the first ARB to show a promising role in reducing
      cardiovascular risk in high-risk patients. This article will highlight the role
      of telmisartan in cardioprotection, underlying specifically the results of two
      major randomized controlled trials: ONTARGET (ONgoing Telmisartan Alone and in
      combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan
      Randomized AssessmeNt Study in aCE-iNtolerant subjects with cardiovascular
      Disease).

PMID- 22140320
TI  - Effect of alcohol and tobacco use on vascular dementia: a matched case control
      study.
AB  - BACKGROUND: Vascular dementia is the second most common type of dementia in the
      United States. The underlying association of tobacco and alcohol with vascular
      dementia is not completely understood. PURPOSE: Determine the relationship of
      tobacco and alcohol use with the development of vascular dementia (VaD). METHODS:
      This was a matched case-control study of subjects living in Olmsted County, MN.
      Cases of VaD were identified through medical record abstraction using
      conventionally accepted definitions of VaD, using the National Institute of
      Neurological Disorders and Stroke and the Association Internationale pour la
      Recherche et l'Ensignement en Neurosicences ( NINDS-AIRENS) criteria and were
      matched to controls by gender and age within 3 years among persons free of
      dementia on the index date. Exposure data for alcohol and tobacco use were
      abstracted by trained nurses, along with demographic, lifestyle, cerebrovascular,
      cardiovascular, and vascular comorbid disease characteristics. Matched
      conditional logistic regression for univariate and multivariate evaluation of the
      association of tobacco and alcohol use with VaD was utilized. RESULTS: Current
      alcohol exposure was associated with a decreased risk of VaD with an odds ratio
      of 0.48 (95% confidence interval: 0.31-0.74). This protective effect of alcohol
      was seen in men, women, and subjects under 80 years of age. Tobacco use was not
      associated with VaD in univariate and multivariate analysis, and stratified
      analysis did not reveal any subgroup-specific associations between tobacco use
      and VaD in the study population. CONCLUSION: Current alcohol use appears to have
      protective effects against the development of vascular dementia. The effects are
      more pronounced in subjects under age 80. This may reflect the direct vascular
      effects of alcohol on the vascular system or may represent a surrogate for better
      social or functional status. Previous alcohol use was not protective. Tobacco use
      was not a risk factor for VaD status, which was possibly an indication of
      survivorship bias in the cohort.

PMID- 22140321
TI  - IL-6-induced pathophysiology during pre-eclampsia: potential therapeutic role for
      magnesium sulfate?
AB  - Pre-eclampsia is defined as new onset hypertension with proteinuria during
      pregnancy. Pre-eclampsia is also characterized by endothelial cell activation and
      dysfunction and intrauterine growth restriction. Preeclamptic women display a
      chronic inflammatory response characterized by elevated inflammatory cytokines,
      circulating monocytes, neutrophils, and T and B lymphocytes secreting
      autoantibodies that activate the angiotensin II type I receptor (AT1-AA).
      Although the pathophysiology of pre-eclampsia is becoming more defined, the
      genesis of the disease is still largely unknown. Furthermore, the only treatment
      for extreme forms of the disease is bed rest and administration of magnesium
      sulfate to sustain the pregnancy a few days prior to early delivery of the fetus,
      which can lead to devastating neurological and physical effects for the newborn.
      Administration of magnesium sulfate is routinely given without adverse effects.
      The focus of this review is to discuss the cascade of events leading to
      cytokines, specifically interleukin-6 (IL-6), in stimulating vasoactive
      substances such as AT1-AA (Figure 1) and to examine the mechanism whereby
      administration of magnesium sulfate can be beneficial during pre-eclampsia. One
      area is to decrease vascular resistance index parameters determined by Doppler
      velocimetry. Another potential area of benefit with magnesium sulfate
      administration may be to decrease inflammatory responses or decrease
      cardiovascular mechanisms stimulated by overexpression of inflammatory cytokines
      in response to placental ischemia or animal models of elevated IL-6 during
      pregnancy. Further studies identifying IL-6-driven mechanisms playing a role in
      the development of hypertension during pregnancy and how administration of
      magnesium sulfate can suppress them are critical to improve decisions affecting
      patient care in women with pre-eclampsia. The results of these types of studies
      will be advantageous to further our knowledge of the pathophysiological
      ramifications associated with pre-eclampsia and to further therapeutic
      development for this disease.

PMID- 22140322
TI  - Effectiveness of interventions to prevent mother-to-child transmission of HIV in
      Southern Ethiopia.
AB  - BACKGROUND: In Ethiopia, Progress in Reducing Mother-to-Child-Transmission
      (PMTCT) of human immunodeficiency virus (HIV) is being curtailed by behavioral
      and cultural factors that continue to put unborn children at risk, and mother-to
      child transmission is responsible for more than 90% of HIV infection in children.
      The objective of this study was to assess PMTCT services by examining knowledge
      about reducing vertical transmission among pregnant women. METHODS: A multistaged
      sampling institution-based survey was conducted in 113 pregnant women in Arba
      Minch. Qualitative and quantitative data were obtained. RESULTS: Of the 113
      respondents, 89.4% were from Arba Minch, 43.4% were at least 25 years of age,
      73.4% had formal education at primary level or above, 100% reported acceptance of
      voluntary counseling and testing, 92.0% were knowledgeable about mother-to-child
      transmission, and 90.3% were aware of the availability of the PMTCT service in
      the health facility. Of 74 HIV-positive women in PMTCT, only three (4.1%) had had
      skilled birth attendants at delivery. There was an unacceptable degree of loss of
      women from PMTCT. Maternal educational level had a statistical association with
      income (P < 0.001) and voluntary counseling and testing for pregnant women (P <
      0.05). Factors that determined use of PMTCT included culture, socioeconomic
      status, and fear of stigma and discrimination. CONCLUSION: In the area studied,
      intervention to reduce mother-to-child transmission of HIV is failing to reach
      its goal. This is an alarming discovery requiring quick reconsideration and
      strengthening of preventive strategies at all levels.

PMID- 22140323
TI  - Prevalence of gestational diabetes and associated maternal and neonatal
      complications in a fast-developing community: global comparisons.
AB  - BACKGROUND: The prevalence of gestational diabetes (GDM) is increasing all over
      the world. Hence, the impact of GDM on maternal and infant health is an important
      topic of research. No study has been conducted in Qatar to evaluate the outcome
      of pregnancies complicated by diabetes mellitus. OBJECTIVE: The aim of the study
      was to determine the prevalence of GDM, compare the maternal-neonatal
      complications among women with GDM and non-GDM pregnant women, and investigate
      the risk factors and potential outcomes associated with GDM. DESIGN: This is a
      prospective cohort study. SETTING: The survey was carried out at the antenatal
      clinics of the Women's Hospital, Qatar. SUBJECTS AND METHODS: A representative
      sample of 2056 pregnant women who attended the antenatal clinics of the Women's
      Hospital were surveyed during the period from the first week of January 2010 to
      April 2011. From this sample, 1608 women (78.2%) expressed their consent to
      participate in the study. Questionnaires were administered to pregnant women who
      were seeking antenatal care at this urban hospital. The questionnaire covered
      variables related to sociodemographic factors, family history, medical history,
      maternal complications, and neonatal outcome. RESULTS: The prevalence of GDM in
      Qatar was 16.3%. Women with GDM were significantly higher in the age group of 35
      45 years (45%; P = 0.001). Family history of diabetes (31.7%; P < 0.001),
      increased parity (55.3%; P = 0.004), and obesity (59.2%; P < 0.001) were
      determinants of GDM in pregnant women. Maternal complications like pregnancy
      induced hypertension (19.1% vs 10.3%; P < 0.001), pre-eclampsia (7.3% vs 3.8%; P
      = 0.012), antepartum hemorrhage (19.2% vs 14.6%; P = 0.05), and cesarean (27.9%
      vs 12.4%; P < 0.001) were significantly higher in GDM women. Neonates were at
      increased risk of preterm birth (12.6% vs 8.3%; P = 0.03), macrosomia (10.3% vs
      5.9%; P = 0.01), and birth trauma (8% vs 3%; P < 0.001). CONCLUSION: The study
      findings revealed that GDM was higher in women in Qatar and that they were at
      increased risk of developing maternal and neonatal complications. Obesity emerged
      as an essential risk factor for subsequent GDM. The advanced maternal age, low
      monthly income, family history of diabetes, and obesity were the main significant
      risk factors for GDM.

PMID- 22140324
TI  - Acute coronary syndrome in women of reproductive age.
AB  - BACKGROUND: There is scarce or no data on prevalence and presentation of acute
      coronary syndrome (ACS) among women of reproductive age. Furthermore, whether
      women of reproductive age presenting with ACS have the same risk factors as men
      and older women is not known. OBJECTIVE: To analyze factors associated with ACS
      in women of reproductive age in comparison with older women and men of a similar
      age group. METHODOLOGY: A total of 9702 cases of acute coronary syndrome over a 3
      year period ( 2006-2008) from the National Cardiovascular Disease database were
      analyzed, with focus on women of reproductive age (20-<40 years), looking into
      association with ethnicity, comorbid illness, and the ACS stratum. Comparison
      with older women (40-<60 years; Control 1) and men of similar age group (Control
      2) was made and analyzed using Fisher's exact test and chi-square test when
      necessary. RESULTS: From a total of 9702 cases, 2344 (24.2%) were women. Of
      these, 45 (1.9%) were women between 20 and <40 years, which is significantly
      lower than the two controls (older women 30.8%, and men of same age 6.2%,
      respectively; P < 0.0001). The distribution of ethnicity shows a similar pattern
      between the study group and the controls, but patients of Indian ethnicity were
      over-represented when compared with the Malaysian demographics of general
      population (31.3% versus 7.1%; P < 0.0001). ACS in women of reproductive age was
      associated with diabetes mellitus in 37.8%, hypertension in 40.0%, and
      dyslipidemia in 24.4% of cases, similar to men of the same age but significantly
      lower than the older women (P < 0.0001). Smoking is not a major risk factor in
      the study group, where only 6.7% ever smoked, similar to older women (6.8%, P =
      1.000) and significantly much less compared with men of the same age (84.1%; P <
      0.0001). Regarding the ACS stratum, a significantly higher percentage of women in
      the study group had ST-segment elevation myocardial infarction compared with
      older women (P = 0.0085) but less than that of men of similar age (P = 0.0187).
      CONCLUSION: ACS is rare in women of reproductive age. Diabetes, hypertension, and
      Indian ethnicity were identified as important contributors.

PMID- 22140325
TI  - Laparoscopic management of a fallopian tubal torsion complicated by a large
      hydrosalpinx.
AB  - Clinical presentation of an adnexal mass is often non-specific and may mimic a
      range of gynecological pathology, as well as renal or gastrointestinal causes of
      lower abdominal pain. While a common entity, its association with a fallopian
      tube pathology is very uncommon. Imaging such as ultrasound has been diagnostic
      in the evaluation of a pelvic mass, and has been reported as assisting the
      diagnosis of fallopian tubal torsion. A pelvic mass of cystic nature can be
      removed by cystectomy, while treatment options for a torted fallopian tube
      include surgical detorsion if detected early, or a salpingectomy should there be
      evidence of necrosis. We report a rare case of fallopian tube torsion complicated
      by a large hydrosalpinx which was managed by laparoscopic surgery.

PMID- 22140326
TI  - Predictors of cervical cancer being at an advanced stage at diagnosis in Sudan.
AB  - BACKGROUND: Cervical cancer is the second most common cancer among women in
      Sudan, with more than two-thirds of all women with invasive cervical cancer being
      diagnosed at an advanced stage (stages III and IV). The lack of a screening
      program for cervical cancer in Sudan may contribute to the late presentation of
      this cancer, but other factors potentially associated with advanced stages of
      cervical cancer at diagnosis are unknown. The purpose of this research was to
      investigate the relationship between age, marital status, ethnicity, health
      insurance coverage, residence in an urban vs a rural setting, and stage (at
      diagnosis) of cervical cancer in Sudan. METHODS: This was a cross sectional study
      of 197 women diagnosed with different stages of cervical cancer. Data was
      obtained from the cancer registry unit at the Radiation and Isotopes Centre in
      Khartoum for all women diagnosed with cervical cancer in 2007. RESULTS: THERE WAS
      AN ASSOCIATION BETWEEN OLDER AGE AND ADVANCED STAGE (AT DIAGNOSIS) OF CERVICAL
      CANCER (ODDS RATIO [OR]: 1.03, 95% confidence interval [CI]: 1.01-1.05). Being of
      African ethnicity was associated with 76% increased odds (OR: 1.76, 95% CI: 1.01
      3.05), living in a rural area was associated with 13% increased odds (OR: 1.13,
      95% CI: 1.78-5.50), and being uninsured was associated with an almost eight-fold
      increase in odds (OR: 7.7, 95% CI: 3.76-15.38). Marital status and education
      level were not associated with an advanced stage of cervical cancer at diagnosis.
      CONCLUSION: Women with cervical cancer who are elderly, not covered by health
      insurance, of African ethnicity, and living in a rural area are more likely to be
      diagnosed at an advanced stage of cervical cancer in Sudan. These women should be
      targeted for cervical cancer screening and a health education program, and
      encouraged to have health insurance.

PMID- 22140328
TI  - Poor reproductive health among a group of socially damaged Middle Eastern women:
      a cross-sectional study.
AB  - BACKGROUND: Despite the scope of violence against women and its importance for
      reproductive health, few data are available on the reproductive health issues
      among women having experienced violence. METHODS: This study described the
      reproductive disorders complicating social harm among 98 socially damaged women
      seeking care from drop-in centers who were of Persian ancestry, able to
      communicate and comprehend the contents of the questionnaire, and had history of
      domestic violence. The questionnaire had five dimensions: demographics,
      reproductive health, sexual performance, sexual behavior, and violence.
      Reproductive health included data on gestation, unplanned pregnancy, abortion,
      contraception, and cervical cancer screening. Data on sexual performance was
      acquired via the Persian version of sexual function scale, which has been
      demonstrated to have acceptable external validity in Iranian population. For
      sexual function, data was gathered on age at first intercourse and whether a
      participant had ever engaged in an oral or anal sexual activity. RESULTS: Mean
      age of participants was 33.4 years. Forty-seven percent of participants were
      married, 34.8% were divorced, 9.8% were widowed, and 8.7% were single. Mean age
      at first marriage was 16.4 (4.3) years and mean age at first sexual relationship
      was 16 (3.9) years. Illiteracy was observed among 18.5% of participants.
      Elementary education was reported by 22.8%, while only 3.3% of participants
      reported academic studies. Fifty-five percent were unemployed and 44.6% reported
      to be working at the time of the study. It was observed that 72.8% of
      participants were inflicted physically, as well as emotionally and sexually. The
      violence was reported to be exerted by husband (42.6%), parents (38.4%), or both
      (19.0%). Among 39 participants who ran away from home, 38 participants reported
      to be inflicted by violence. Unwanted pregnancy was reported by 64.6% of the
      participants. Abortion was reported in 50.0% of participants. Contraception was
      completely ignored in 44.6% of participants. Among eligible women, 53.3% never
      participated in cervical cancer screening examination. Mean sexual performance
      scale score was 21.9 (5.5) and 75 (83.3%) participants scored less than 28.
      CONCLUSION: A high prevalence of poor reproductive health was documented among a
      group of Middle Eastern socially damaged women.

PMID- 22140329
TI  - Revision of the Southeast Asian millipede genus Orthomorpha Bollman, 1893, with
      the proposal of a new genus (Diplopoda, Polydesmida, Paradoxosomatidae).
AB  - The large genus Orthomorpha is rediagnosed and is shown to currently comprise 51
      identifiable species ranging from northern Myanmar and Thailand in the Northwest
      to Lombok Island, Indonesia in the Southeast. Of them, 20 species have been
      revised and/or abundantly illustrated, based on a restudy of mostly type
      material; further 12 species are described as new: Orthomorpha atypicasp. n.,
      Orthomorpha communissp. n., Orthomorpha isarankuraisp. n., Orthomorpha
      picturatasp. n., Orthomorpha similanensissp. n., Orthomorpha suberectasp. n.,
      Orthomorpha tuberculiferasp. n.,Orthomorpha subtuberculiferasp. n. and
      Orthomorpha latitergasp. n., all from Thailand, as well as Orthomorpha elevatasp.
      n.,Orthomorpha spiniformissp. n. and Orthomorpha subelevatasp. n., from northern
      Malaysia. The type-species Orthomorpha beaumontii (Le Guillou, 1841) is
      redescribed in due detail from male material as well, actually being a senior
      subjective synonym of Orthomorpha spinala (Attems, 1932), syn. n. Two additional
      new synonymies are proposed: Orthomorpha rotundicollis (Attems, 1937) =
      Orthomorpha tuberculata (Attems, 1937), syn. n., and Orthomorpha butteli Carl,
      1922 = Orthomorpha consocius Chamberlin, 1945, syn. n., the valid names to the
      left. All species have been keyed and all new and some especially widespread
      species have been mapped. Further six species, including two revised from type
      material, are still to be considered dubious, mostly because their paraterga
      appear to be too narrow to represent Orthomorpha species. A new genus,
      Orthomorphoidesgen. n., diagnosed versus Orthomorpha through only moderately well
      developed paraterga, coupled with a poorly bi- or trifid gonopod tip, with at
      least some of its apical prongs being short spines, is erected for two species:
      Orthomorpha setosus (Attems, 1937), the type-species, which is also revised from
      type material, and Orthomorpha exaratus (Attems, 1953), both comb. n. ex
      Orthomorpha.

PMID- 22140330
TI  - Review of the oriental monotypic genus pibrocha kirkaldy (hemiptera,
      fulgoromorpha, fulgoridae, dorysarthrinae).
AB  - The monotypic genus Pibrocha Kirkaldy, 1902, known only from Sri Lanka in the
      Oriental region, is closely related to Dorysarthrus Puton, 1895 from southwestern
      Asia and northern Africa (Palaearctic region). The genusis revised to include a
      first description of the male genital structures and a discussion of
      relationships between Pibrocha, Dorysarthrus and Dichoptera Spinola, 1839. A
      diagnostic key to the three genera and photos of their type species are provided
      for better comparison in these taxa. Pibrocha is assigned tentatively from
      Dictyopharidae to the subfamily Dorysarthrinae (Fulgoridae).

PMID- 22140327
TI  - Immunopharmacology of ulipristal as an emergency contraceptive.
AB  - A new progesterone antagonist, ulipristal has been made available as an emergency
      contraceptive. Ulipristal's major mechanism of action as an emergency
      contraceptive has been ascribed to its ability to delay ovulation beyond the life
      span of the sperm. This paper analyzes the potential action of ulipristal (1)
      when unprotected intercourse and administration of ulipristal occur outside the
      fertility window and (2) when unprotected intercourse and administration of
      ulipristal occur at or within 24 hours of ovulation. When unprotected intercourse
      and the use of a single low dose of ulipristal occur outside of the fertility
      window, ulipristal behaves like a placebo. When unprotected intercourse and the
      use of a single low dose of ulipristal occur within the fertility window but
      before ovulation, ulipristal behaves like an emergency contraceptive by delaying
      ovulation and thereby preventing fertilization. When unprotected intercourse and
      the administration of ulipristal occur at or within 24 hours of ovulation, then
      ulipristal has an abortifacient action. It is proposed that the abortifacient
      mechanism of a low dose of ulipristal taken after fertilization but before
      implantation is due to the ability of ulipristal to block the maternal innate
      immune system to become immunotolerant to the paternal allogenic embryo.
      Progesterone's critical immunotolerant actions involving early pregnancy factor,
      progesterone-induced blocking factor, and uterine natural killer cells are
      compromised by ulipristal.

PMID- 22140331
TI  - Taxonomic review of the genus Tambinia Stal (Hemiptera, Fulgoromorpha,
      Tropiduchidae) with descriptions of four new species from the Pacific region.
AB  - Four new species of Tambinia Stal (Hemiptera: Fulgoromorpha: Tropiduchidae),
      Tambinia conussp. n. (Papua New Guinea), Tambinia maculasp. n. (Malaysia:
      Borneo), Tambinia robustocarinasp. n. (Malaysia: Sabah) and Tambinia
      sexmaculatasp. n. (Australia: Kuranda) are described and illustrated from the
      Pacific region. The diagnostic characters of this genus are redefined. A
      checklist and a key to the known species of Tambinia are provided.

PMID- 22140332
TI  - Taxonomic remarks about Semiclivina (Kult, 1947) new status, with description of
      Uroclivina subgen. n., and of two new species from South America (Coleoptera,
      Carabidae, Scaritinae, Clivinini).
AB  - The subgenus Semiclivina Kult, 1947 of Clivina Latreille, 1802 (sensu lato) has
      been re-ranked as a genus, with the most readily observed feature being the
      stridulation organ of the proepisterna and front femora. A group of species
      within Semiclivina is characterized by a peculiar acute tubercle at the posterior
      margin of the eye, which corresponds to an equally noticeable incision of the
      anterior margin of the pronotum. This group is considered as monophyletic and
      placed as such in the subgen. n.Uroclivina. The species Semiclivina (Uroclivina)
      bergerisp. n. from Argentina and southern Brazil and Semiclivina (Uroclivina)
      schmidisp. n. from French Guyana are described. The following additional species
      are included in Uroclivina: Clivina urophthalmoides (Kult, 1947) new combination,
      Clivina urophthalma (Putzeys, 1863) new combination, and Clivina oxyomma
      (Putzeys, 1868) new combination. The two subgenera of Semiclivina Kult, and the
      current five species of Uroclivina are differentiated in a key.

PMID- 22140333
TI  - Two new Neotropical species of Ceracis Mellie (Coleoptera, Ciidae) and
      redefinition of the cucullatus group.
AB  - Two new Neotropical species of Ceracis Mellie are described: Ceracis cassumbensis
      Antunes-Carvalho & Lopes-Andrade, sp. n. from a single locality in northeastern
      Brazil and Ceracis navarretei Antunes-Carvalho & Lopes-Andrade, sp. n. from a
      single locality in southern Mexico. Scanning Electron Microscope images of adults
      and photographs of holotypes and male terminalia are provided for both species,
      their similarities and differences with other Ceracis are briefly discussed, and
      the cucullatus species-group is redefined for including the new species described
      herein.

PMID- 22140334
TI  - Michanthidium almeidai, a new species from northeastern Brazil (Hymenoptera,
      Megachilinae).
AB  - A new species of Michanthidium Urban (Hymenoptera, Megachilinae)is described and
      figured from Sergipe and Bahia States, northeastern Brazil. An identification
      key, illustrations, and a distribution map for the three species of the genus are
      presented. The male genitalia of Michanthidium almeidaisp. n. and Michanthidium
      albitarse are illustrated and compared for the first time.

PMID- 22140335
TI  - Biometry based ageing of nestling Indian Spotted Owlets ( Athene brama brama).
AB  - Biometric analysis helps in sex differentiation, understanding development and
      for studies of avian biology such as foraging ecology, evolutionary ecology, and
      survivorship. We suggest that biometry can also be a reliable, practical and
      inexpensive tool to determine the age of nestlings in the field by non-invasive
      methods. As an example we studied the biometry of wing, culmen, talon, tarsus and
      body mass of nestling southern Indian Spotted Owlets (Athene brama brama). Based
      on the growth pattern analysis using logistic growth model, discriminant analysis
      and CHAID (Chi-squared Automatic Interaction Detection) based decision tree, we
      show that biometry of nestling Spotted Owlets is an easy, reliable and
      inexpensive method to determine nestling age and to assess growth rate and
      relative nutritional status. These biometric parameters also allow us to predict
      their ability to initiate first flight from the nest site. This method is
      described here for the first time and we postulate that such charts can be
      devised for other avian species as well, so as to assist conservation biologists
      and bird rescuers.

PMID- 22140336
TI  - Annotated catalogue of the Haliplidae of China with the description of a new
      species and new records from China (Coleoptera, Adephaga).
AB  - A revised checklist of Haliplidae (Coleoptera: Adephaga) of China is presented. A
      new species Haliplus (Haliplus) latreilleisp. n. is described from Guizhou,
      China. Three species, Haliplus (Haliplidius) confinis Stephens, Haliplus
      (Haliplus) ruficollis (De Geer) and Haliplus (Haliplus) sibricus Motschulsky are
      reported from China for the first time. Haliplus dalmatinus Muller is excluded
      from the list of Chinese species. A number of new provincial records from China
      is presented.

PMID- 22140337
TI  - Three new species and reassessment of the rare Neotropical ant genus
      Leptanilloides (Hymenoptera, Formicidae, Leptanilloidinae).
AB  - We describe three new species of the Neotropical ant genus Leptanilloides:
      Leptanilloides gracilissp. n. based on workers from Mexico and Guatemala,
      Leptanilloides erinyssp. n. based on workers and a gyne from Ecuador, and
      Leptanilloides femoralissp. n. based on workers from Venezuela. The description
      of Leptanilloides gracilis is a northern extension of the known range of the
      genus, now numbering eleven described species. We also describe and discuss three
      unassociated male morphotypes from Central America. We report the occurrence of a
      metatibial gland in Leptanilloides and a fused promesonotal connection (suture)
      in some species. We provide a modified, detailed diagnosis of the genus and a
      revised key to the worker caste of the known species.

PMID- 22140338
TI  - Revision of the Paridris nephtaspecies group (Hymenoptera, Platygastroidea,
      Platygastridae).
AB  - The Paridris nephta group is revised (Hymenoptera: Platygastridae). Fifteen
      species are described, 14 of which are new: Paridris atroxTalamas, sp. n.(Yunnan
      Province, China), Paridris bununTalamas, sp. n.(Taiwan), Paridris ferusTalamas,
      sp. n.(Thailand), Paridris kagemonoTalamas, sp. n.(Japan), Paridris
      minatorTalamas, sp. n.(Laos, Thailand), Paridris mystaxTalamas, sp. n.(Laos,
      Thailand), Paridris nephta(Kozlov) (Japan, North Korea, South Korea, Far Eastern
      Russia), Paridris nilakaTalamas, sp. n.(Thailand), Paridris reptilisTalamas, sp.
      n.(Taiwan), Paridris rugulosusTalamas, sp. n.(Laos, Vietnam), Paridris
      solarisTalamas, sp. n.(Laos, Thailand, Vietnam), Paridris teresTalamas, sp.
      n.(Vietnam), Paridris toketokiTalamas, sp. n.(Taiwan), Paridris
      verrucosusTalamas, sp. n.(Guangdong Province, China), Paridris yakTalamas, sp.
      n.(Thailand).

PMID- 22140339
TI  - Erotylidae (Insecta, Coleoptera) of Poland - problematic taxa, updated keys and
      new records.
AB  - New data concerning the occurrence of pleasing fungus beetles (Coleoptera:
      Erotylidae) in Poland are given, with a focus on rare and difficult to identify
      Central European taxa. Cryptophilus cf. integer (Heer) (Cryptophilinae) is
      reported from the Polish territory for the first time based on adult and larval
      specimens collected in the Wielkopolska-Kujawy Lowland. Identification problems
      concerning species of Cryptophilus introduced to Europe are discussed. Triplax
      carpathica Reitter (Erotylinae) is recorded from the Bialowieza Primeval Forest,
      which is the first known non-Carpathian finding of this species, located in the
      close proximity of the Polish-Belarussian UNESCO World Heritage Site "Bialowieza
      Forest". Discussion of Triplax carpathica being conspecific with Siberian Triplax
      rufiventris Gebler is provided. New Polish localities of several other Erotylidae
      are reported, and an updated key to Central European species of Triplax is given.
      The Triplax key is supplemented with dorsal and ventral habitus images of all
      treated Triplax species. One of the rarest Central European erotyline species
      Combocerus glaber (Schaller) is recorded from xerothermic grasslands in North
      West Poland.

PMID- 22140340
TI  - Two new Typhloreicheia species from Sardinia and their biogeographical
      significance (Coleoptera, Carabidae, Scaritinae).
AB  - Typhloreicheia monachasp. n. and Typhloreicheia ilianaesp. n. are described from
      two caves of Central-Eastern Sardinia (Nuoro province): the Bue Marino cave and
      the Nurra 'e Pradu cave, respectively. Both caves are located in the part of the
      island where many highly specialised subterranean carabid beetles are localised.
      Typhloreicheia monacha is apparently related to two other species of the same
      area, i.e. Typhloreicheia onnisi Casale & Magrini, 2004 and Typhloreicheia
      elegans (Dodero, 1916); Typhloreicheia ilianae is closely related to
      Typhloreicheia henroti Jeannel, 1957, known from a cave near Dorgali.
      Relationships and diagnostic features among these taxa are discussed and
      illustrated, and a key for identification of the specialised subterranean
      Typhloreicheia species of Sardinia is provided. The hypothesis of adaptive
      radiation of Reicheiina species in Sardinia, recently proposed by the senior
      author of this contribution, is further elaborated in light of new data.

PMID- 22140341
TI  - A review of the genus Serangium Blackburn (Coleoptera, Coccinellidae) from China.
AB  - The genus Serangium Blackburn from China is reviewed. The genus Catanella
      Miyatake is removed from synonymy with Serangium. Serangium baculum Xiao is
      transferred to Catanella, as Catanella baculum (Xiao), comb. n. Twelve species of
      Serangium are described, keyed and illustrated, including eight new species,
      Serangium magnipunctatum Wang & Ren, sp. n., Serangium trimaculatum Wang & Ren,
      sp. n., Serangium centrale Wang & Ren, sp. n., Serangium leigongicus Wang & Ren,
      sp. n., Serangium latilobum Wang & Ren, sp. n., Serangium digitiforme Wang & Ren,
      sp. n., Serangium dulongjiang Wang, Ren & Chen, sp. n., and Serangium contortum
      Wang & Ren, sp. n.Serangium punctum Miyatake is newly recorded from China.

PMID- 22140342
TI  - Entedoninae wasps (Hymenoptera, Chalcidoidea, Eulophidae) associated with ants
      (Hymenoptera, Formicidae) in tropical America, with new species and notes on
      their biology.
AB  - Three new species of Eulophidae associated, or presumed to be associated with
      ants are described: two species of Horismenus Walker and one species of
      Microdonophagus Schauff. Information on the biology is also included. The two
      Horismenus species are from Chiapas, Mexico. Horismenus myrmecophagussp. n. is
      known only from females and is a gregarious endoparasitoid in larvae of the
      weaver ant Camponotus sp. ca. textor. The parasitoids pupate inside the host
      larva, and an average of 6.7 individuals develops per host. This is the second
      time a species of genus Horismenus is found parasitizing the brood of a formicine
      ant of genus Camponotus. Horismenus microdonophagussp. n. is described from both
      males and females, and is a gregarious endoparasitoid attacking the larvae of
      Microdon sp. (Diptera: Syrphidae), a predator on ant brood found in nests of
      Camponotus sp. ca. textor. The new species of Microdonophagus, Microdonophagus
      tertius, is from Costa Rica, and known only from the female. Nothing is known
      about its biology but since another species in same genus, Microdonophagus
      woodleyi Schauff, is associated with ants through its host, Microdon larva (with
      same biology as Horismenus microdonophagus), it is possible that also
      Microdonophagus tertius has this association. A new distributional record for
      Microdonophagus woodleyi is also reported, extending its distribution from Panama
      and Colombia to Brazil.

PMID- 22140343
TI  - The indigenous honey bees of Saudi Arabia (Hymenoptera, Apidae, Apis mellifera
      jemenitica Ruttner): Their natural history and role in beekeeping.
AB  - Apis mellifera jemenitica Ruttner (= yemenitica auctorum: videEngel 1999) has
      been used in apiculture throughout the Arabian Peninsula since at least 2000 BC.
      Existing literature demonstrates that these populations are well adapted for the
      harsh extremes of the region. Populations of Apis mellifera jemenitica native to
      Saudi Arabia are far more heat tolerant than the standard races often imported
      from Europe. Central Saudi Arabia has the highest summer temperatures for the
      Arabian Peninsula, and it is in this region where only Apis mellifera jemenitica
      survives, while other subspecies fail to persist. The indigenous race of Saudi
      Arabia differs from other subspecies in the region in some morphological,
      biological, and behavioral characteristics. Further taxonomic investigation, as
      well as molecular studies, is needed in order to confirm whether the Saudi
      indigenous bee populations represent a race distinct from Apis mellifera
      jemenitica, or merely an ecotype of this subspecies.

PMID- 22140344
TI  - Tetraclita ehsani sp. n. (Cirripedia, Tetraclitidae), a common intertidal
      barnacle from the Gulf of Oman, Iran.
AB  - A new species of intertidal acorn barnacle Tetraclita ehsanisp. n. was identified
      from the Iranian coast in the Gulf of Oman. Tetraclita ehsanisp. n. inhabits low
      exposed rocky shores and also attaches to shells of molluscs and the barnacle
      Megabalanus species. Parietes of Tetraclita ehsani ranged from white to pink
      which is different from Tetraclita serrata (in South African waters), which has
      green parietes. Morphology of the tergum and cirrus III of Tetraclita ehsanisp.
      n. is distinctive from other described West Indian Ocean species which have pink
      or white parietes (Tetraclita rufotincta, Tetraclita achituvi and Tetraclita
      reni). The tergum of Tetraclita ehsani is very narrow and the basal margin is
      slightly concave or straight, in contrast to Tetraclita rufotincta and Tetraclita
      reni, in which the tergum are board and with a very concave basal margin. Cirrus
      I anterior ramus of both Tetraclita ehsani and Tetraclita reni is antenniform and
      thus differing from the cirrus I of Tetraclita rufotincta (see Chan et al. 2009).
      Cirrus III of Tetraclita ehsanisp. n. is non-antenniform and lacks multicuspidate
      type setae, which is different from Tetraclita reni by having an antenniform
      cirrus III and with multicuspidate setae.

PMID- 22140345
TI  - A new genus and species of deep-sea glass sponge (Porifera, Hexactinellida,
      Aulocalycidae) from the Indian Ocean.
AB  - New hexactinellid sponges were collected from 2589 m depth on the Carlsberg Ridge
      in the Indian Ocean during deep-sea dredging. All fragments belong to a new genus
      and species, Indiellagen. n.ridgenensissp. n., a representative of the family
      Aulocalycidae described here. The peculiar features of this sponge, not described
      earlier for other Aulocalycidae, are: longitudinal strands present in several
      layers and epirhyses channelization.

PMID- 22140346
TI  - First record of the littoral family Isotogastruridae (Collembola) in Asia.
AB  - The new species Isotogastrura trichaetosasp. n. isdescribed from a sand beach of
      Hainan, South China. It differs from all its congeners by 3+3 axial setae on Abd.
      IV (vs. 2+2) and by the presence of a pair of tubercles on Abd.VI. The geography
      of this strictly littoral genus is discussed.

PMID- 22140347
TI  - The genus Ectonura Cassagnau, 1980in South Africa (Collembola, Neanuridae,
      Neanurinae), with a key to South African Neanurinae.
AB  - Two new species of Neanurinae (Collembola) are described from the Western Cape,
      South Africa: Ectonura monochaetasp. n. and Ectonura barraisp. n.Ectonura
      monochaetasp. n. differs from other species in the genus by its strongly reduced
      chaetotaxy, and the lateral shift of dorso-internal chaetae on Abd. V and their
      integration in the tubercles (De+DL). Ectonura barraisp. n. is similar to
      Ectonura natalensis (Womersley, 1934), but differs in chaetotaxic details and
      chaetal group arrangement. A key to the seven species of Neanurinae recorded from
      South Africa is given.

PMID- 22140348
TI  - Larvae and a new species of Ancyronyx Erichson, 1847 (Insecta, Coleoptera,
      Elmidae) from Palawan, Philippines, using DNA sequences for the assignment of the
      developmental stages.
AB  - Ancyronyx montanussp. n. is described based on adults and larvae, matched using
      their cox1 DNA sequence data. Larvae of six additional species of Ancyronyx
      Erichson, 1847 were also described here for the first time, aided by cox1 or cob
      data: Ancyronyx helgeschneideri Freitag & Jach, 2007, Ancyronyx minerva Freitag &
      Jach, 2007, Ancyronyx patrolus Freitag & Jach, 2007, Ancyronyx procerus Jach,
      1994, Ancyronyx punkti Freitag & Jach, 2007, Ancyronyx pseudopatrolus Freitag &
      Jach, 2007. Ancyronyx procerus is newly recorded from the Philippines by a larval
      specimen from Busuanga island. The new species and larval stages are described in
      detail and illustrated by digital and SEM images. A key to the Ancyronyx larvae
      of Palawan and an updated checklist of Philippine Ancyronyx is provided.

PMID- 22140349
TI  - A new species of Cisaris (Hymenoptera, Ichneumonidae, Cryptinae) with a key to
      the world species.
AB  - A new species, Cisaris canaliculatus Sun & Sheng, sp. n., belonging to the tribe
      Phygadeuontini of the subfamily Cryptinae (Hymenoptera: Ichneumonidae), collected
      from Jiangxi Province, China, is reported. A key to the species of the genus
      Cisaris Townes, 1970, is provided.

PMID- 22140350
TI  - Redescription and revision of the Neotropical genus Pseudoheptascelio Szabo
      (Hymenoptera, Platygastridae, Scelioninae), parasitoids of eggs of short-horned
      grasshoppers (Orthoptera, Acrididae).
AB  - The genus Pseudoheptascelio Szabo is redescribed and its species revised. We
      recognize four species: Pseudoheptascelio muesebecki Szabo, Pseudoheptascelio
      cornopis Masner, Pseudoheptascelio ticosp. n. and Pseudoheptascelio rexsp. n. The
      genus is found from Guatemala south to the Brazilian state of Rio Grande do Sul.
      The species Pseudoheptascelio cornopis is recorded as a parasitoid of the eggs of
      Cornops aquaticum (Bruner) on water hyacinth, Eichhornia crassipes (Mart.) Solms.

PMID- 22140351
TI  - Terror, Resource Gains and Exclusionist Political Attitudes among New Immigrants
      and Veteran Israelis.
AB  - This study analyses the antecedents of exclusionist political attitudes towards
      Palestinian citizens of Israel among Israeli immigrants from the former Soviet
      Union in comparison to Old Jewish Israelis (OJI). A large-scale study of
      exclusionist political attitudes was conducted in the face of ongoing terrorism
      in Israel through telephone surveys carried out in September 2003 with 641 OJI
      and 131 immigrants. The main goal of the survey was to estimate the influence of
      perceived loss and gain of resources-as a consequence of terror-on attitudes
      towards Palestinian Israelis, while controlling for other relevant predictors of
      exclusionism-i.e. authoritarianism or threat perception. Findings obtained via
      interaction analyses and structural equation modelling show that a) immigrants
      display higher levels of exclusionist political attitudes towards Palestinian
      citizens of Israel than OJI; b) loss of resources, authoritarianism, and hawkish
      (rightist) worldviews predict exclusionist political attitudes among both
      immigrants and non-immigrants; c) failure to undergo post-traumatic growth
      (resource gain) in response to terrorism (e.g. finding meaning in life, becoming
      closer to others) is a significant predictor of exclusionist political attitudes
      only among immigrants.

PMID- 22140352
TI  - New Developments in the Field of Monoliths for Chromatography.

PMID- 22140353
TI  - Disability: a welfarist approach.
AB  - In this paper, we offer a new account of disability. According to our account,
      some state of a person's biology or psychology is a disability if that state
      makes it more likely that a person's life will get worse, in terms of his or her
      own wellbeing, in a given set of social and environmental circumstances. Unlike
      the medical model of disability, our welfarist approach does not tie disability
      to deviation from normal species' functioning, nor does it understand disability
      in essentialist terms. Like the social model of disability, the welfarist
      approach sees disability as a harmful state that results from the interaction
      between a person's biology and psychology and his or her surrounding environment.
      However, unlike the social model, it denies that the harm associated with
      disability is entirely due to social prejudice or injustice. In this paper, we
      outline and clarify the welfarist approach, answer common objections and
      illustrate its usefulness in addressing a range of difficult ethical questions
      involving disability.

PMID- 22140355
TI  - Sampling Development.
AB  - Research in developmental psychology requires sampling at different time points.
      Accurate depictions of developmental change provide a foundation for further
      empirical studies and theories about developmental mechanisms. However,
      overreliance on widely spaced sampling intervals in cross-sectional and
      longitudinal designs threatens the validity of the enterprise. This article
      discusses how to sample development in order to accurately discern the shape of
      developmental change. The ideal solution is daunting: to summarize behavior over
      24-hour intervals and collect daily samples over the critical periods of change.
      We discuss the magnitude of errors due to undersampling, and the risks associated
      with oversampling. When daily sampling is not feasible, we offer suggestions for
      sampling methods that can provide preliminary reference points and provisional
      sketches of the general shape of a developmental trajectory. Denser sampling then
      can be applied strategically during periods of enhanced variability, inflections
      in the rate of developmental change, or in relation to key events or processes
      that may affect the course of change. Despite the challenges of dense repeated
      sampling, researchers must take seriously the problem of sampling on a
      developmental time scale if we are to know the true shape of developmental
      change.

PMID- 22140354
TI  - A new look at glutamate and ischemia: NMDA agonist improves long-term functional
      outcome in a rat model of stroke.
AB  - Ischemic stroke triggers a massive, although transient, glutamate efflux and
      excessive activation of NMDA receptors (NMDARs), possibly leading to neuronal
      death. However, multiple clinical trials with NMDA antagonists failed to improve,
      or even worsened, stroke outcome. Recent findings of a persistent post-stroke
      decline in NMDAR density, which plays a pivotal role in plasticity and memory
      formation, suggest that NMDAR stimulation, rather than inhibition, may prove
      beneficial in the subacute period after stroke. AIM: This study aims to examine
      the effect of the NMDAR partial agonist d-cycloserine (DCS) on long-term
      structural, functional and behavioral outcomes in rats subjected to transient
      middle cerebral artery occlusion, an animal model of ischemic stroke.  MATERIALS
      #ENTITYSTARTX00026; METHODS: Rats (n = 36) that were subjected to 90 min of
      middle cerebral artery occlusion were given a single injection of DCS (10 mg/kg)
      or vehicle (phosphate-buffered saline) 24 h after occlusion and followed up for
      30 days. MRI (structural and functional) was used to measure infarction, atrophy
      and cortical activation due to electrical forepaw stimulation. Memory function
      was assessed on days 7, 21 and 30 postocclusion using the novel object
      recognition test. A total of 20 nonischemic controls were included for
      comparison.  RESULTS: DCS treatment resulted in significant improvement of
      somatosensory and cognitive function relative to vehicle treatment. By day 30,
      cognitive performance of the DCS-treated animals was indistinguishable from
      nonischemic controls, while vehicle-treated animals demonstrated a stable memory
      deficit. DCS had no significant effect on infarction or atrophy.  CONCLUSION:
      These results support a beneficial role for NMDAR stimulation during the recovery
      period after stroke, most likely due to enhanced neuroplasticity rather than
      neuroprotection.

PMID- 22140356
TI  - The Contribution of Infant, Maternal, and Family Conditions to Maternal Feeding
      Competencies.
AB  - OBJECTIVE: Because little is known about the role of family problem-solving
      processes in the development of mothers' competencies in feeding a very low birth
      weight (VLBW) infant, we explored the contribution made by the competence in
      negotiating displayed by a mother and family member as they jointly problem solve
      infant-care issues. The infant's neonatal biomedical condition, maternal
      depressive symptoms, and family poverty status may also contribute to feeding
      competencies.  DESIGN: A sample of 41 mothers of VLBW infants from 2 longitudinal
      studies who were observed during feeding at 1 and 8 months infant postterm age,
      with a family member of their choosing, participated in a dyadic problem-solving
      exercise. We assessed maternal feeding competencies with the Parent-Child Early
      Relational Assessment (Clark, 1997) and dyadic negotiating competence using an
      observational scale from the Iowa Family Interaction Rating Scales (Melby &
      Conger, 2001). We classified infant condition through medical record audit.
      Maternal depressive symptoms were assessed with the Center for Epidemiologic
      Studies-Depression (CES-D) Scale (L. S. Radloff, 1977), and family poverty status
      was determined through the mother's report of family income.  RESULTS: Mothers'
      feeding competencies, structured into 2 factors, Parental Positive Affective
      Involvement, Sensitivity, and Responsiveness (PPAISR) and Parental Negative
      Affect and Behavior (PNAB, scored in the direction of low negativity) were stable
      from 1 to 8 months, accounting for the entire set of predictor variables.
      Neonatal biomedical condition had no effect on either PPAISR or PNAB; depressive
      symptoms were negatively associated with PNAB at 8 months; poverty status
      negatively predicted both PPAISR and PNAB at 1 and 8 months; and negotiating
      competence of the mother-family member dyad was positively associated with PNAB
      at 1 month.  CONCLUSIONS: Evidence that family poverty status and dyadic
      negotiating competence were both associated with maternal feeding competencies
      supports inclusion of these family-level variables in a model of feeding
      competencies. A mother's negotiating competence with another family member who
      takes a responsible role in infant care may support maternal feeding competencies
      during a VLBW infant's early weeks when parenting patterns are forming.

PMID- 22140358
TI  - Electrostatically biased binding of kinesin to microtubules.
AB  - The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests
      that such minimal motor domains generate force by a biased binding mechanism, in
      which they preferentially select binding sites on the microtubule that lie ahead
      in the progress direction of the motor. A specific molecular mechanism for biased
      binding has, however, so far been lacking. Here we use atomistic Brownian
      dynamics simulations combined with experimental mutagenesis to show that incoming
      kinesin heads undergo electrostatically guided diffusion-to-capture by
      microtubules, and that this produces directionally biased binding. Kinesin-1
      heads are initially rotated by the electrostatic field so that their tubulin
      binding sites face inwards, and then steered towards a plus-endwards binding
      site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence
      (RAK) in kinesin helix alpha-6 is predicted to be important for electrostatic
      guidance. Real-world mutagenesis of this sequence powerfully influences kinesin
      driven microtubule sliding, with one mutant producing a 5-fold acceleration over
      wild type. We conclude that electrostatic interactions play an important role in
      the kinesin stepping mechanism, by biasing the diffusional association of kinesin
      with microtubules.

PMID- 22140357
TI  - Repressive LTR nucleosome positioning by the BAF complex is required for HIV
      latency.
AB  - Persistence of a reservoir of latently infected memory T cells provides a barrier
      to HIV eradication in treated patients. Several reports have implicated the
      involvement of SWI/SNF chromatin remodeling complexes in restricting early steps
      in HIV infection, in coupling the processes of integration and remodeling, and in
      promoter/LTR transcription activation and repression. However, the mechanism
      behind the seemingly contradictory involvement of SWI/SNF in the HIV life cycle
      remains unclear. Here we addressed the role of SWI/SNF in regulation of the
      latent HIV LTR before and after transcriptional activation. We determined the
      predicted nucleosome affinity of the LTR sequence and found a striking reverse
      correlation when compared to the strictly positioned in vivo LTR nucleosomal
      structure; sequences encompassing the DNase hypersensitive regions displayed the
      highest nucleosome affinity, while the strictly positioned nucleosomes displayed
      lower affinity for nucleosome formation. To examine the mechanism behind this
      reverse correlation, we used a combinatorial approach to determine DNA
      accessibility, histone occupancy, and the unique recruitment and requirement of
      BAF and PBAF, two functionally distinct subclasses of SWI/SNF at the LTR of HIV
      infected cells before and after activation. We find that establishment and
      maintenance of HIV latency requires BAF, which removes a preferred nucleosome
      from DHS1 to position the repressive nucleosome-1 over energetically sub-optimal
      sequences. Depletion of BAF resulted in de-repression of HIV latency concomitant
      with a dramatic alteration in the LTR nucleosome profile as determined by high
      resolution MNase nucleosomal mapping. Upon activation, BAF was lost from the HIV
      promoter, while PBAF was selectively recruited by acetylated Tat to facilitate
      LTR transcription. Thus BAF and PBAF, recruited during different stages of the
      HIV life cycle, display opposing function on the HIV promoter. Our data point to
      the ATP-dependent BRG1 component of BAF as a putative therapeutic target to
      deplete the latent reservoir in patients.

PMID- 22140360
TI  - Dissecting HIV's latent menace.

PMID- 22140359
TI  - Copy number variation of KIR genes influences HIV-1 control.
AB  - A genome-wide screen for large structural variants showed that a copy number
      variant (CNV) in the region encoding killer cell immunoglobulin-like receptors
      (KIR) associates with HIV-1 control as measured by plasma viral load at set point
      in individuals of European ancestry. This CNV encompasses the KIR3DL1-KIR3DS1
      locus, encoding receptors that interact with specific HLA-Bw4 molecules to
      regulate the activation of lymphocyte subsets including natural killer (NK)
      cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1
      positive cohort, and showed that an increase in KIR3DS1 count associates with a
      lower viral set point if its putative ligand is present (p = 0.00028), as does an
      increase in KIR3DL1 count in the presence of KIR3DS1 and appropriate ligands for
      both receptors (p = 0.0015). We further provide functional data that demonstrate
      that NK cells from individuals with multiple copies of KIR3DL1, in the presence
      of KIR3DS1 and the appropriate ligands, inhibit HIV-1 replication more robustly,
      and associated with a significant expansion in the frequency of KIR3DS1+, but not
      KIR3DL1+, NK cells in their peripheral blood. Our results suggest that the
      relative amounts of these activating and inhibitory KIR play a role in regulating
      the peripheral expansion of highly antiviral KIR3DS1+ NK cells, which may
      determine differences in HIV-1 control following infection.

PMID- 22140361
TI  - Why full open access matters.

PMID- 22140362
TI  - Voluntary medical male circumcision: an introduction to the cost, impact, and
      challenges of accelerated scaling up.
AB  - Scaling up voluntary medical male circumcision (VMMC) for HIV prevention is cost
      saving and creates fiscal space in the future that otherwise would have been
      encumbered by antiretroviral treatment costs. An investment of US$1,500,000,000
      between 2011 and 2015 to achieve 80% coverage in 13 priority countries in
      southern and eastern Africa will result in net savings of US$16,500,000,000.
      Strong political leadership, country ownership, and stakeholder engagement, along
      with effective demand creation, community mobilisation, and human resource
      deployment, are essential. This collection of articles on determining the cost
      and impact of VMMC for HIV prevention signposts the way forward to scaling up
      VMMC service delivery safely and efficiently to reap individual- and population
      level benefits.

PMID- 22140363
TI  - Voluntary medical male circumcision: logistics, commodities, and waste management
      requirements for scale-up of services.
AB  - BACKGROUND: The global HIV prevention community is implementing voluntary medical
      male circumcision (VMMC) programs across eastern and southern Africa, with a goal
      of reaching 80% coverage in adult males by 2015. Successful implementation will
      depend on the accessibility of commodities essential for VMMC programming and the
      appropriate allocation of resources to support the VMMC supply chain. For this,
      the United States President's Emergency Plan for AIDS Relief, in collaboration
      with the World Health Organization and the Joint United Nations Programme on
      HIV/AIDS, has developed a standard list of commodities for VMMC programs. METHODS
      AND FINDINGS: This list of commodities was used to inform program planning for a
      1-y program to circumcise 152,000 adult men in Swaziland. During this process,
      additional key commodities were identified, expanding the standard list to
      include commodities for waste management, HIV counseling and testing, and the
      treatment of sexually transmitted infections. The approximate costs for the
      procurement of commodities, management of a supply chain, and waste disposal,
      were determined for the VMMC program in Swaziland using current market prices of
      goods and services. Previous costing studies of VMMC programs did not capture
      supply chain costs, nor the full range of commodities needed for VMMC program
      implementation or waste management. Our calculations indicate that depending upon
      the volume of services provided, supply chain and waste management, including
      commodities and associated labor, contribute between US$58.92 and US$73.57 to the
      cost of performing one adult male circumcision in Swaziland. CONCLUSIONS:
      Experience with the VMMC program in Swaziland indicates that supply chain and
      waste management add approximately US$60 per circumcision, nearly doubling the
      total per procedure cost estimated previously; these additional costs are used to
      inform the estimate of per procedure costs modeled by Njeuhmeli et al. in
      "Voluntary Medical Male Circumcision: Modeling the Impact and Cost of Expanding
      Male Circumcision for HIV Prevention in Eastern and Southern Africa." Program
      planners and policy makers should consider the significant contribution of supply
      chain and waste management to VMMC program costs as they determine future
      resource needs for VMMC programs.

PMID- 22140364
TI  - Voluntary medical male circumcision: strategies for meeting the human resource
      needs of scale-up in southern and eastern Africa.
AB  - Voluntary medical male circumcision (VMMC) reduces female-to-male HIV
      transmission by approximately 60%; modeling suggests that scaling up VMMC to 80%
      of men 15- to 49-years-old within five years would avert over 3.3 million new HIV
      infections in 14 high priority countries/regions in southern and eastern Africa
      by 2025 and would require 20.33 million circumcisions. However, the shortage of
      health professionals in these countries must be addressed to reach these proposed
      coverage levels. To identify human resource approaches that are being used to
      improve VMMC volume and efficiency, we looked at previous literature and
      conducted a program review. We identified surgical efficiencies, non-surgical
      efficiencies, task shifting, task sharing, temporary redeployment of public
      sector staff during VMMC campaign periods, expansion of the health workforce
      through recruitment of unemployed, recently retired, newly graduating, or on
      leave health care workers, and the use of volunteer medical staff from other
      countries as approaches that address human resource constraints. Case studies
      from Kenya, Tanzania, and Swaziland illustrate several innovative responses to
      human resource challenges. Although the shortage of skilled personnel remains a
      major challenge to the rapid scale-up of VMMC in the 14 African priority
      countries/regions, health programs throughout the region may be able to replicate
      or adapt these approaches to scale up VMMC for public health impact.

PMID- 22140365
TI  - Voluntary medical male circumcision: translating research into the rapid
      expansion of services in Kenya, 2008-2011.
AB  - Since the World Health Organization and the Joint United Nations Programme on
      HIV/AIDS recommended implementation of medical male circumcision (MC) as part of
      HIV prevention in areas with low MC and high HIV prevalence rates in 2007, the
      government of Kenya has developed a strategy to circumcise 80% of uncircumcised
      men within five years. To facilitate the quick translation of research to
      practice, a national MC task force was formed in 2007, a medical MC policy was
      implemented in early 2008, and Nyanza Province, the region with the highest HIV
      burden and low rates of circumcision, was prioritized for services under the
      direction of a provincial voluntary medical male circumcision (VMMC) task force.
      The government's early and continuous engagement with community leaders/elders,
      politicians, youth, and women's groups has led to the rapid endorsement and
      acceptance of VMMC. In addition, several innovative approaches have helped to
      optimize VMMC scale-up. Since October 2008, the Kenyan VMMC program has
      circumcised approximately 290,000 men, mainly in Nyanza Province, an
      accomplishment made possible through a combination of governmental leadership, a
      documented implementation strategy, and the adoption of appropriate and
      innovative approaches. Kenya's success provides a model for others planning VMMC
      scale-up programs.

PMID- 22140366
TI  - Voluntary medical male circumcision: matching demand and supply with quality and
      efficiency in a high-volume campaign in Iringa Region, Tanzania.
AB  - The government of Tanzania has adopted voluntary medical male circumcision (VMMC)
      as an important component of its national HIV prevention strategy and is scaling
      up VMMC in eight regions nationwide, with the goal of reaching 2.8 million
      uncircumcised men by 2015. In a 2010 campaign lasting six weeks, five health
      facilities in Tanzania's Iringa Region performed 10,352 VMMCs, which exceeded the
      campaign's target by 72%, with an adverse event (AE) rate of 1%. HIV testing was
      almost universal during the campaign. Through the adoption of approaches designed
      to improve clinical efficiency-including the use of the forceps-guided surgical
      method, the use of multiple beds in an assembly line by surgical teams, and task
      shifting and task sharing-the campaign matched the supply of VMMC services with
      demand. Community mobilization and bringing client preparation tasks (such as
      counseling, testing, and client scheduling) out of the facility and into the
      community helped to generate demand. This case study suggests that a campaign
      approach can be used to provide high-volume quality VMMC services without
      compromising client safety, and provides a model for matching supply and demand
      for VMMC services in other settings.

PMID- 22140367
TI  - Voluntary medical male circumcision: modeling the impact and cost of expanding
      male circumcision for HIV prevention in eastern and southern Africa.
AB  - BACKGROUND: There is strong evidence showing that voluntary medical male
      circumcision (VMMC) reduces HIV incidence in men. To inform the VMMC policies and
      goals of 13 priority countries in eastern and southern Africa, we estimate the
      impact and cost of scaling up adult VMMC using updated, country-specific data.
      METHODS AND FINDINGS: We use the Decision Makers' Program Planning Tool (DMPPT)
      to model the impact and cost of scaling up adult VMMC in Botswana, Lesotho,
      Malawi, Mozambique, Namibia, Rwanda, South Africa, Swaziland, Tanzania, Uganda,
      Zambia, Zimbabwe, and Nyanza Province in Kenya. We use epidemiologic and
      demographic data from recent household surveys for each country. The cost of VMMC
      ranges from US$65.85 to US$95.15 per VMMC performed, based on a cost assessment
      of VMMC services aligned with the World Health Organization's considerations of
      models for optimizing volume and efficiencies. Results from the DMPPT models
      suggest that scaling up adult VMMC to reach 80% coverage in the 13 countries by
      2015 would entail performing 20.34 million circumcisions between 2011 and 2015
      and an additional 8.42 million between 2016 and 2025 (to maintain the 80%
      coverage). Such a scale-up would result in averting 3.36 million new HIV
      infections through 2025. In addition, while the model shows that this scale-up
      would cost a total of US$2 billion between 2011 and 2025, it would result in net
      savings (due to averted treatment and care costs) amounting to US$16.51 billion.
      CONCLUSIONS: This study suggests that rapid scale-up of VMMC in eastern and
      southern Africa is warranted based on the likely impact on the region's HIV
      epidemics and net savings. Scaling up of safe VMMC in eastern and southern Africa
      will lead to a substantial reduction in HIV infections in the countries and lower
      health system costs through averted HIV care costs.

PMID- 22140368
TI  - Voluntary medical male circumcision: a framework analysis of policy and program
      implementation in eastern and southern Africa.
AB  - BACKGROUND: Following confirmation of the effectiveness of voluntary medical male
      circumcision (VMMC) for HIV prevention, the World Health Organization and the
      Joint United Nations Programme on HIV/AIDS issued recommendations in 2007. Less
      than 5 y later, priority countries are at different stages of program scale-up.
      This paper analyzes the progress towards the scale-up of VMMC programs. It
      analyzes the adoption of VMMC as an additional HIV prevention strategy and
      explores the factors may have expedited or hindered the adoption of policies and
      initial program implementation in priority countries to date. METHODS AND
      FINDINGS: VMMCs performed in priority countries between 2008 and 2010 were
      recorded and used to classify countries into five adopter categories according to
      the Diffusion of Innovations framework. The main predictors of VMMC program
      adoption were determined and factors influencing subsequent scale-up explored. By
      the end of 2010, over 550,000 VMMCs had been performed, representing
      approximately 3% of the target coverage level in priority countries. The "early
      adopter" countries developed national VMMC policies and initiated VMMC program
      implementation soon after the release of the WHO recommendations. However, based
      on modeling using the Decision Makers' Program Planning Tool (DMPPT), only Kenya
      appears to be on track towards achievement of the DMPPT-estimated 80% coverage
      goal by 2015, having already achieved 61.5% of the DMPPT target. None of the
      other countries appear to be on track to achieve their targets. Potential
      predicators of early adoption of male circumcision programs include having a VMMC
      focal person, establishing a national policy, having an operational strategy, and
      the establishment of a pilot program. CONCLUSIONS: Early adoption of VMMC
      policies did not necessarily result in rapid program scale-up. A key lesson is
      the importance of not only being ready to adopt a new intervention but also
      ensuring that factors critical to supporting and accelerating scale-up are
      incorporated into the program. The most successful program had country ownership
      and sustained leadership to translate research into a national policy and
      program. Please see later in the article for the Editors' Summary.

PMID- 22140369
TI  - What research is needed to stop TB? Introducing the TB Research Movement.

PMID- 22140370
TI  - Characterization and rapid sampling of protein folding Markov state model
      topologies.
AB  - Markov state models (MSMs) have proven themselves to be effective statistical and
      quantitative models for understanding protein folding dynamics. As stochastic
      networks, MSMs allow for descriptions of parallel folding pathways and facilitate
      quantitative comparison to experiments conducted at the ensemble level. While
      this complex network structure is advantageous in many respects, a simple
      topological description of these graphs is elusive. In this paper, we compare a
      series of protein folding MSMs to the topology of the Cayley tree, a graph
      structure on which dynamics are intuitive. We go on to introduce and test new
      sampling schemes that have potential to improve automated model construction, a
      critical step toward making Markov state modeling more accessible to general
      users.

PMID- 22140373
TI  - Transport in two-dimensional paper networks.
AB  - Two-dimensional paper networks (2DPNs) hold great potential for transcending the
      capabilities and performance of today's paper-based analytical devices.
      Specifically, 2DPNs enable sophisticated multi-step chemical processing sequences
      for sample pretreatment and analysis at a cost and ease-of-use that make them
      appropriate for use in settings with low resources. A quantitative understanding
      of flow in paper networks is essential to realizing the potential of these
      networks. In this report, we provide a framework for understanding flow in simple
      2DPNs using experiments, analytical expressions, and computational simulations.

PMID- 22140374
TI  - CDH3-Related Syndromes: Report on a New Mutation and Overview of the Genotype
      Phenotype Correlations.
AB  - Hypotrichosis with juvenile macular dystrophy (HJMD) and ectodermal dysplasia,
      ectrodactyly and macular dystrophy (EEM) are both caused by mutations in the CDH3
      gene. In this report, we describe a family with EEM syndrome caused by a novel
      CDH3 gene mutation and review the mutation spectrum and limb abnormalities in
      both EEM and HJMD. A protein structure model showing the localization of
      different mutations causing both syndromes is presented. The CDH3 gene was
      sequenced and investigation of the mutations performed using a protein structure
      model. The conservation score was calculated by ConSurf. We identified a novel
      CDH3 gene mutation, p.G277V, which resides in a conserved residue located on a
      beta-strand in the second cadherin domain. Review of the data on previously
      published mutations showed intra-familial and inter-familial variations in the
      severity of the limb abnormalities. Syndactyly was the most consistent clinical
      finding present in all the patients regardless of mutation type. The results of
      our study point to a phenotypic continuum between HJMD and EEM. It is important
      for genetic counseling to keep in mind the possible clinical/phenotypic overlap
      between these 2 syndromes and to be aware of the possible risk of limb
      abnormalities in future pregnancies in families with HJMD syndrome. CDH3 gene
      mutation screening is recommended in patients with both these syndromes as part
      of the work-up in order to offer appropriate genetic counseling.

PMID- 22140375
TI  - Severe Myoclonic Epilepsy in Infancy - Adult Phenotype with Bradykinesia,
      Hypomimia, and Perseverative Behavior: Report of Five Cases.
AB  - Dravet syndrome or severe myoclonic epilepsy in infancy (SMEI) is an epileptic
      syndrome characterised by refractory epilepsy and intellectual disability,
      typically presenting with febrile and afebrile generalised and unilateral
      clonic/tonic-clonic seizures in the first year of life and other types of
      seizures appearing later in the course of the disease. Five adult patients with
      SMEI and SCN1A mutations are reported, in which motor and behavioural
      abnormalities were outstanding symptoms. Bradykinesia, responding with latency,
      slow speaking with a thin voice, midface hypomimia and perseveration were
      distinctive features in all cases. These symptoms may be fit to define the adult
      phenotype of SMEI beyond seizure/epilepsy criteria. The motor and behavioural
      symptoms are discussed in the context of a possibly underlying frontal
      lobe/mesofrontal and cerebellar dysfunction.

PMID- 22140376
TI  - Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a
      Patient with Van den Ende-Gupta Syndrome.
AB  - Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by
      craniofacial and skeletal manifestations, specifically blepharophimosis, malar
      and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long
      slender bones of the hands and feet. To date, only 24 patients have been
      described. It is generally thought that the syndrome is transmitted by an
      autosomal recessive mode of inheritance, although evidence for genetic
      heterogeneity has recently been presented. We report on a girl followed from
      birth up to 3 years of life with a set of peculiar minor anomalies,
      arachnocamptodactyly of hands and feet, characteristic of VDEGS in association
      with a 22q11.12 deletion. Recently, the VDEGS gene was mapped to the DiGeorge
      syndrome region on 22q11.2, and homozygous mutations in the SCARF2 gene were
      identified. We now report the first patient with VDEGS due to compound
      heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2
      splice site mutation.

PMID- 22140377
TI  - Sixteen New Cases Contributing to the Characterization of Patients with Distal
      22q11.2 Microduplications.
AB  - The chromosome region 22q11.2 has long been recognized to be susceptible to
      genomic rearrangement. More recently, this genomic instability has been shown to
      extend distally (involving LCR22E-H) to the commonly deleted/duplicated region.
      To date, 21 index cases with 'distal' 22q11.2 duplications have been reported. We
      report on the clinical and molecular characterization of 16 individuals with
      distal 22q11.2 duplications identified by DNA microarray analysis. Two of the
      individuals have been partly described previously. The clinical phenotype varied
      among the patients in this study, although the majority displayed various degrees
      of developmental delay and speech disturbances. Other clinical features included
      behavioral problems, hypotonia, and dysmorphic facial features. Notably, none of
      the patients was diagnosed with a congenital heart defect. We found a high degree
      of inherited duplications. Additional copy number changes of unclear clinical
      significance were identified in 5 of our patients, and it is possible that these
      may contribute to the phenotypic expression in these patients as has been
      suggested recently in a 2-hit 'digenic' model for 16p12.1 deletions. The varied
      phenotypic expression and incomplete penetrance observed for distal 22q11.2
      duplications makes it exceedingly difficult to ascribe pathogenicity for these
      duplications. Given the observed enrichment of the duplication in patient samples
      versus healthy controls, it is likely that distal 22q11.2 duplications represent
      a susceptibility/risk locus for speech and mild developmental delay.

PMID- 22140378
TI  - FOXD1 Duplication Causes Branchial Defects and Interacts with the TFAP2A Gene
      Implicated in the Branchio-Oculo-Facial Syndrome in Causing Eye Effects in
      Zebrafish.
AB  - Branchio-oculo-facial syndrome (BOFS) is a rare disorder characterized by
      maldevelopment of the first and second branchial arches, skin defects, facial
      dysmorphism, auricular, ophthalmological and oral abnormalities. A high clinical
      variability has been reported. Recently, mutations in TFAP2A were found to
      underlie this condition. A small duplication on 5q13 was detected in 2 family
      members with mild BOFS features. Molecular cytogenetic delineation of the
      duplication demonstrated that only 7 genes are affected: LOC100289045, RGNEF,
      UTP15, ANKRA2, FUNDC2P1, BTF3 and FOXD1. The latter is expressed in the
      developing branchial arches and involved in cranio-facial development. Zebrafish
      embryos with combined inhibition of the expression of foxd1l and tfap2a show
      optic axis defects. We identified a novel locus associated with a mild BOFS-like
      phenotype. The functional in vivo experiments suggest an interaction between
      FOXD1 and TFAP2A.

PMID- 22140379
TI  - Refinement of the Region for Split Hand/Foot Malformation 5 on 2q31.1.
AB  - Background: Deletions that encompass 2q31.1 have been proposed as a microdeletion
      syndrome with common clinical features, including intellectual
      disability/developmental delay, microcephaly, cleft palate, growth delay, and
      hand/foot anomalies. In addition, several genes within this region have been
      proposed as candidates for split hand-foot malformation 5 (SHFM5). Methods: To
      delineate the genotype-phenotype correlation between deletions of this region, we
      identified 14 individuals with deletions at 2q31.1 detected by microarray
      analysis for physical and developmental disabilities. Results: All subjects for
      whom detailed clinical records were available had neurological deficits of
      varying degree. Seven subjects with deletions encompassing the HOXD cluster had
      hand/foot anomalies of varying severity, including syndactyly, brachydactyly, and
      ectrodactyly. Of 7 subjects with deletions proximal to the HOXD cluster, 5 of
      which encompassed DLX1/DLX2, none had clinically significant hand/foot anomalies.
      In contrast to previous reports, the individuals in our study did not display a
      characteristic gestalt of dysmorphic facial features. Conclusion: The absence of
      hand/foot anomalies in any of the individuals with deletions of DLX1/DLX2 but not
      the HOXD cluster supports the hypothesis that haploinsufficiency of the HOXD
      cluster, rather than DLX1/DLX2, accounts for the skeletal abnormalities in
      subjects with 2q31.1 microdeletions.

PMID- 22140380
TI  - Biomimetic Precipitation of Uniaxially Grown Calcium Phosphate Crystals from Full
      Length Human Amelogenin Sols.
AB  - Human dental enamel forms over a period of 2 - 4 years by substituting the enamel
      matrix, a protein gel mostly composed of a single protein, amelogenin with
      fibrous apatite nanocrystals. Self-assembly of a dense amelogenin matrix is
      presumed to direct the growth of apatite fibers and their organization into
      bundles that eventually comprise the mature enamel, the hardest tissue in the
      mammalian body. This work aims to establish the physicochemical and biochemical
      conditions for the synthesis of fibrous apatite crystals under the control of a
      recombinant full-length human amelogenin matrix in combination with a
      programmable titration system. The growth of apatite substrates was initiated
      from supersaturated calcium phosphate solutions in the presence of dispersed
      amelogenin assemblies. It was shown earlier and confirmed in this study that
      binding of amelogenin onto apatite surfaces presents the first step that leads to
      substrate-specific crystal growth. In this work, we report enhanced nucleation
      and growth under conditions at which amelogenin and apatite carry opposite
      charges and adsorption of the protein onto the apatite seeds is even more
      favored. Experiments at pH below the isoelectric point of amelogenin showed
      increased protein binding to apatite and at low Ca/P molar ratios resulted in a
      change in crystal morphology from plate-like to fibrous and rod-shaped.
      Concentrations of calcium and phosphate ions in the supernatant did not show
      drastic decreases throughout the titration period, indicating controlled
      precipitation from the protein suspension metastable with respect to calcium
      phosphate. It is argued that ameloblasts in the developing enamel may vary the
      density of the protein matrix at the nano scale by varying local pH, and thus
      control the interaction between the mineral and protein phases. The biomimetic
      experimental setting applied in this study has thus proven as convenient for
      gaining insight into the fundamental nature of the process of amelogenesis.

PMID- 22140381
TI  - Hepatitis B vaccination reliability in celiac disease.

PMID- 22140382
TI  - Hepatitis E virus and renal transplantation.

PMID- 22140383
TI  - Recent advances in the management of chronic hepatitis B.
AB  - There are seven approved treatments for adults with chronic hepatitis B virus
      infection in the United States and European countries: interferon-alpha,
      pegylated interferon-alpha, lamivudine, adefovir dipivoxil, entecavir,
      telbivudine, and tenofovir disoproxil fumarate. At present, two new analogues,
      entecavir and tenofovir are recommended as the first line therapy by the
      guidelines of European Association for the Study of the Liver and American
      Association Study for the Liver Diseases. On the other hand, regarding interferon
      therapy, use of pegylated interferon-alpha is recommended as the first line
      therapy instead of standard interferon-alpha by both guidelines. Therefore, the
      main scientific interests and unmet medical needs for treatment of chronic
      hepatitis B have been narrowed down to long-term efficacy and safety of the two
      said analogues-entecavir and tenofovir-and combination therapy of pegylated
      interferon-alpha with the two analogues. To put it concretely, further studies
      are needed to assess (1) the long-term efficacy and safety and resistance to
      entecavir and tenofovir; (2) the efficacy of different durations (24 weeks to 2
      years) and lower doses of pegylated interferon-alpha; (3) the role of combination
      therapy with two analogues to reduce resistance; and (4) the efficacy and safety
      of the two analogues with decompensated cirrhosis. Herein, we review the recent
      available data and results.

PMID- 22140384
TI  - Optimal duration of treatment for HCV genotype 1 infection in slow responders: a
      meta-analysis.
AB  - BACKGROUND: A head-to-head comparison of the 72-week and 48-week anti-HCV
      therapies in slow responders with genotype 1 infection has been performed in
      several randomized clinical trials (RCTs). OBJECTIVES: This review aimed at
      summarizing and pooling the results of these studies. MATERIALS AND METHODS: RCTs
      that had evaluated the 72-week vs. 48-week anti-HCV therapy (peginterferon and
      ribavirin) in slow responders with HCV genotype 1 infection were systematically
      identified. A meta-analysis was performed using the random effects model.
      Heterogeneity in results was assessed on the basis of the Q statistics, and
      publication bias was evaluated by using Harbord's modified test. The end point
      was set as a sustained virological response (SVR). RESULTS: Data of 1206 subjects
      were retrieved from 7 studies. A total of 631 patients had received extended
      therapy. Slow virological responders who received the 72-week therapy had a
      significantly higher probability of achieving SVR than their counterpartswho
      received the 48-week therapy [RR = 1.44 (95% CI, 1.20-1.73)]. With regard to
      publication biases, the heterogeneity in funnel plots was not significant (P =
      0.19, I2 = 30%, PHarbord = 0.1). CONCLUSION: Our meta-analysis showed that the 72
      week therapy with peginterferon and ibavirin is significantly superior to the
      standard 48-week therapy in slow responders th HCV genotype 1 infection.

PMID- 22140385
TI  - Ubiquitin conjugation of hepatitis B virus core antigen DNA vaccine leads to
      enhanced cell-mediated immune response in BALB/c mice.
AB  - BACKGROUND: Nearly 350 million persons worldwide are chronically infected with
      hepatitis B virus (HBV). Ubiquitin (Ub) is a highly conserved small regulatory
      protein, ubiquitous in eukaryotes, that usually serves as a signal for the target
      protein that is recognised and degraded in proteasomes . The Ub-mediated
      processing of antigens is rapid and efficient and stimulates cell-mediated immune
      responses. Accordingly, Ub-mediated processing of antigens has been widely used
      in chronic-infection and cancer studies to improve immune response. OBJECTIVES:
      Many clinical trials have shown that DNA vaccine potency needs to be greatly
      enhanced. Here, we report a new strategy for designing an HBV DNA vaccine using
      the ubiquitin (Ub) sequence. The aim of this study was to investigate a novel DNA
      vaccination, based on the expression of HBV core antigen (HBcAg), fused to Ub to
      enhance DNA vaccine potency. MATERIALS AND METHODS: Mouse ubiquitin fused to the
      HBcAg gene and cloned into the eukaryotic vector pcDNA3.1 (-). BALB/c mice were
      immunized with recombinant pUb-HBcAg or pHBcAg DNA vaccine. Lymphocyte
      proliferation assay, intracellular IFN-gamma assay, CTL cytotoxicity assay, and
      antibody assay were performed to analyze the cellular and humoral immune
      responses to our DNA constructs. RESULTS: HBcAg was expressed effectively in the
      COS-7 cells that were transiently transfected with pUb-HBcAg. Strong anti-HBc IgG
      responses were elicited in mice that were immunized with pUb-HBcAg. The endpoint
      titers of anti-HBc peaked at 1:656100 on the 42nd day after the third
      immunization. pUb-HBcAg stimulated greater lymphocyte proliferation and induced
      higher levels of IL-2 and IFN-gamma and a greater percentage of HBcAg-specific
      CD8+ T cells in mice than pHBcAg. In the CTL assay, the specific lysis rate
      reached 56.5% at an effector:target ratio of 50:1 in mice that were immunized
      with pUb-HBcAg. CONCLUSIONS: pUb-HBcAg elicits specific anti-HBc responses and
      induces HBc-specific CTL responses in immunized BALB/c mice. Our results imply
      that Ub can be used as a molecular adjuvant that enhances the potency of DNA
      vaccines.

PMID- 22140386
TI  - Prevalence of chronic hepatitis B and hepatitis C among first time blood donors
      in Northeast Bosnia and Herzegovina: an estimate of prevalence in general
      population.
AB  - BACKGROUND: Data on the epidemiology of hepatitis B and C in Bosnia and
      Herzegovina (B&H) are lacking. OBJECTIVES: To assess the prevalence of hepatitis
      B surface antigen (HBsAg) and anti-hepatitis C virus (anti-HCV) in blood samples
      of first time blood donors in a well-defined region of B&H. Our secondary goal
      was to estimate the prevalence of HBsAg and anti-HCV in the general population of
      the same region. PATIENTS AND METHODS: We evaluated 8196 blood samples for the
      presence of HBsAg and/or anti-HCV, adjusted for differences in gender, and used
      the ratio estimation method to determine the prevalence in the general
      population. RESULTS: We analyzed 1263 (15.4%) female and 6933 (84.6%) male blood
      donors (male-to-female ratio: 5.49 to 1). The adjusted prevalence of HBsAg among
      blood donors was 0.787% (95% CI = 0.535-1.038), while the prevalence of anti-HCV
      was 0.267% (95% CI = 0.016-0.519). There was no difference in the prevalence of
      HBsAg or anti-HCV between men and women. We estimate that the prevalence of HBsAg
      and anti-HCV in the general population is 1.057% to 1.535% and 0.29% to 0.89%,
      respectively. CONCLUSIONS: The prevalence of HBsAg and anti-HCV among blood
      donors suggests that our region has low endemicity for both hepatitis B and
      hepatitis C.

PMID- 22140387
TI  - Is there need for a new hepatitis B vaccine schedule for children with celiac
      disease?
AB  - BACKGROUND: Celiac disease (CD) is an autoimmune disease characterized by
      immunemediated inflammatory damage of the small intestinal mucosa, precipitated
      by the ingestion of gluten-containing foods. Since human leucocyte antigen DQ2
      (HLA-DQ2) is a marker of nonresponsiveness to hepatits B virus (HBV) vaccine, CD
      may also be associated with this nonresponsiveness. OBJECTIVES: The aim of this
      study was to compare the responses to HBV vaccine between children with CD and
      healthy children. We also investigated the relationship between the patients'
      responses to hepatitis B vaccine, the clinical presentation of CD, and dietary
      compliance in the patients. PATIENTS AND METHODS: We recruited 52 children with
      CD and 20 age- and sex-matched healthy children who received HBV vaccination
      according to the standard immunization schedule. The production of specific
      antihepatitis B surface antigen (HBsAg) antibodies was evaluated in all patients
      and control participants. Subjects with less than 10 IU/L anti-HBs were consided
      nonresponders to the vaccination. RESULTS: 31 of the 52 patients (59.6%) were
      female and 21 (40.4%) were male. The mean age of the CD patients was 10.7 +/- 4
      years (range, 4-18 years). Anti-HBs titers were positive in 32 (61.5%) patients
      and negative in 20 (38.5%) patients, while they were positive in 18 (90%) of the
      children in the control group (P < 0.05). We found statistically significant
      differences between negative anti-HBs titers, clinical presentation of CD, and
      dietary compliance in patients with CD (P < 0.05). CONCLUSIONS: Nonresponsiveness
      to hepatitis B vaccination was more frequently found in children with CD than in
      the control group. Therefore, the response to HBV vaccination should be
      investigated in children with CD, and a different immunization schedule may need
      to be developed. Further, compliance to the prescribed gluten-free diet (GFD) may
      improve the immune response to HBV vaccination in children with CD.

PMID- 22140388
TI  - Prevention of hepatitis B recurrence in liver transplant patients using oral
      antiviral therapy without long-term hepatitis B immunoglobulin.
AB  - BACKGROUND: Small studies have suggested that nucleos(t)ide analogue therapy
      (NAT) with reduced hepatitis B immunoglobulin (HBIG) duration may be efficacious
      in preventing post-liver transplantation (LT) HBV recurrence. OBJECTIVES: This
      larger study evaluates the use of NAT with short term (< 6 mo) or no HBIG for
      prevention of post-LT HBV recurrence. PATIENTS AND METHODS: All HBV patients
      undergoing LT at a university transplant center between 2002 and 2007 were
      identified retrospectively. Patient demographics, medication regimen, and adverse
      events were noted. The primary endpoint was HBV recurrence and secondary
      endpoints were graft and patient survival. RESULTS: 28 study patients were
      identified. Of these 28 patients, 4 (14%) received no HBIG, 6 (22%) received only
      inpatient HBIG, and 18 (64%) received inpatient HBIG and outpatient HBIG. 16 of
      the 28 patients (57%) received combination NAT and 12 patients (43%) received
      single NAT. At a median time of 15.5 months (range 9-24 months) post-LT, 4 of the
      28 patients (14%) had recurrent HBV. Of those patients with recurrent HBV, 3
      received both inpatient and outpatient HBIG and 1 received no HBIG. All cases of
      HBV recurrence were associated with noncompliance. CONCLUSIONS: NAT with short
      term or no HBIG was efficacious and safe in preventing post-LT HBV. All compliant
      patients were HBV-free, including 9 patients who received no HBIG or only
      inpatient HBIG. Additional studies using NAT without HBIG appear justified.

PMID- 22140390
TI  - Liver storage disease in Iran: a ten year study of liver biopsies in Children
      Medical Center Hospital in Tehran-Iran.
AB  - BACKGROUND: Liver storage diseases are rare biochemical and inherited diseases
      that affect multiorgan systems. OBJECTIVES: This study was performed to determine
      the rate of storage diseases and their types in liver pathology specimens of
      subjects who were referred to a tertiary pediatric center. PATIENTS AND METHODS:
      Two pathologists evaluated 2216 pathology specimens (stained with hematoxylin and
      eosin and periodic acid-Schiff) from subjects who were referred to the largest
      pediatric tertiary referral center in Iran between 1996 and 2007. Baseline data
      and clinical and laboratory manifestations were retrieved from the patients'
      files. RESULTS: We identified 117 patients who had storage diseases. A
      combination of clinical and laboratory findings was used to assess the final
      diagnosis. Glycogen storage disease (GSD) was observed in 85 of cases, compared
      with lysosomal storage diseases (LSD) in 31 patients and mucopolysaccharidoses in
      1 case. LSD was more prevalent in those aged between 1 month and 1 year, whereas
      GSD was more frequent in those aged between 1 and 6 years. Most of the patients
      aged between 1 and 6 years. Most patients with LSD and GSD had unknown types of
      the disease. The most common known types in the LSD and GSD groups were Niemann
      Pick disease and GSD type I respectively. The most common clinical and laboratory
      manifestation was hepatomegaly and abnormal liver enzymes, respectively.
      CONCLUSIONS: Most of our patients with storage diseases had Gaucher disease.
      Hepatomegaly and elevated transaminase levels were the most striking finding.
      However, with regard to the limitations of our methodology, further studies that
      collect more accurate data are warranted.

PMID- 22140389
TI  - Seroprevalence of hepatitis E among Iranian renal transplant recipients.
AB  - BACKGROUND: Renal transplant recipients are known to be susceptible to viral
      infections, with more severe clinical presentations compared to healthy persons.
      Hepatitis E is generally a self-limited disease, which is caused by hepatitis E
      virus. Recently, hepatitis E has become more important in organ transplant
      recipients, because of new findings regarding the potential for chronic
      infections in this patient group. OBJECTIVES: This study aimed to evaluate the
      seroprevalence of anti-HEV IgG among kidney transplant recipients in Urmia, in
      the north-western region of Iran. PATIENTS AND METHODS: 91 patients were selected
      randomly from amongst patients who had undergone kidney transplantation in Urmia,
      Iran. Each patient was tested for the presence of anti-HEV IgG antibody using an
      enzyme-linked immunosorbent assay (ELISA, Dia.Pro; Diagnostic Bioprobes, Italy).
      RESULTS: 28 subjects (30.8%) were seropositive for anti-HEV IgG. Seropositive
      patients were generally older than seronegative patients (P = 0.009). There was
      no correlation between HEV infection and the level of education (P = 0.206), the
      history of blood transfusion (P = 0.164), or history of pre-transplantation
      hemodialysis (P = 0.228). There was no significant difference in the serum
      alanine aminotransferase (ALT) levels of the anti-HEV seropositive and
      seronegative patients. Multinomial logistic regression analysis indicated no
      significant relationship between HEV infection and increase in ALT levels, even
      after controlling for treatment with azathioprine (P = 0.79, OR = 1.12; 95% CI:
      0.45-2.76). CONCLUSION: The anti-HEV IgG antibody has a high prevalence in
      Iranian kidney transplant recipients, and it is significantly higher in
      comparison with previous studies in the general population or in hemodialysis
      patients.

PMID- 22140391
TI  - Liver injury induced by high-dose methylprednisolone therapy: a case report and
      brief review of the literature.
AB  - Corticosteroids are used widely to treat many types of disease. In general, these
      drugs are considered safe for the liver; however, recent reports have
      demonstrated that high-dose methylprednisolone (MT) may cause severe liver
      injury. Here, we report a case of a 24-year-old female who was given pulsed MT
      therapy for multiple sclerosis. MT induced icteric hepatitis and impaired liver
      synthetic function. Hepatotoxicity developed several weeks after drug exposure,
      and the causal association with MT was confirmed by unintentional rechallenge
      test. A brief review of the literature on corticosteroid-induced hepatotoxicity
      is presented.

PMID- 22140392
TI  - Hepatitis B virus antibody levels in high-risk health care workers.

PMID- 22140393
TI  - Hepatitis B immunization in health care workers: needs and opportunities.

PMID- 22140394
TI  - Risk factors and incidence of hepatocellular carcinoma in Southeast Iran.

PMID- 22140395
TI  - Hepatitis A virus: seroepidemiological study in Fars province.

PMID- 22140396
TI  - A Model for Studying Neuropsychological Effects of Sleep Intervention: The Effect
      of 3-week Continuous Positive Airway Pressure Treatment.
AB  - PURPOSE: Patients with obstructive sleep apnea (OSA) commonly have cognitive
      complaints. There are few randomized studies that have examined
      neuropsychological effects of continuous positive airway pressure (CPAP)
      treatment in patients with OSA. In this double-blind trial, we examined if a 3
      week CPAP treatment compared with placebo CPAP treatment has specific therapeutic
      effects on cognitive impairments in patients with OSA and if there are specific
      domains of cognitive impairments sensitive to 3-week CPAP treatment.  SUBJECTS
      AND METHODS: Thirty-eight newly diagnosed patients with untreated OSA underwent
      neuropsychological testing before and after 3-weeks CPAP or Placebo CPAP
      treatment. The two treatment groups (therapeutic CPAP, and placebo-CPAP) were
      compared using repeated measures analysis of variance (ANOVA).  RESULTS AND
      CONCLUSION: Impairments in neuropsychological functioning ranged from 2.6% to
      47.1% before treatment. In response to 3 weeks of treatment, there was no
      significant time by treatment interaction for a global deficit score of
      neuropsychological functioning. Only the Stroop Color (number correct) test
      showed significant improvement specific to CPAP treatment. The study demonstrates
      the importance of further randomized placebo controlled studies in this area.

PMID- 22140397
TI  - The Symptom Cluster of Sleep, Fatigue and Depressive Symptoms in Breast Cancer
      Patients: Severity of the Problem and Treatment Options.
AB  - Breast cancer is the most commonly diagnosed cancer in women. Insomnia is a
      significant problem in breast cancer patients, affecting between 20% to 70% of
      newly diagnosed or recently treated cancer patients. Pain, fatigue, anxiety, and
      depression are also common conditions in breast cancer and often co-occur with
      insomnia in symptom clusters, exacerbating one another, and decreasing quality of
      life (QOL). There have been no clinical trials of drugs for sleep in cancer.
      Cognitive behavioral psychotherapies on the other hand, have shown some of the
      most positive results in alleviating the distressing symptoms that often
      accompany the breast cancer experience, but even these studies have not targeted
      the symptom cluster. Pharmacological as well as non-pharmacological treatments
      need to be explored. It might be that a combined pharmacological and behavioral
      treatment is most efficacious. In short, substantially more research is needed to
      fully understand and treat the symptom cluster of insomnia, fatigue, pain,
      depression and anxiety in breast cancer.

PMID- 22140398
TI  - Nanoscale porosity in polymer films: fabrication and therapeutic applications.
AB  - This review focuses on current developments in the field of nanostructured bulk
      polymers and their application in bioengineering and therapeutic sciences. In
      contrast to well-established nanoscale materials, such as nanoparticles and
      nanofibers, bulk nanostructured polymers combine nanoscale structure in a
      macroscopic construct, which enables unique application of these materials.
      Contemporary fabrication and processing techniques capable of producing
      nanoporous polymer films are reviewed. Focus is placed on techniques capable of
      sub-100 nm features since this range approaches the size scale of biological
      components, such as proteins and viruses. The attributes of these techniques are
      compared, with an emphasis on the characteristic advantages and limitations of
      each method. Finally, application of these materials to biofiltration,
      immunoisolation, and drug delivery are reviewed.

PMID- 22140400
TI  - "Hitting the wall": Lived experiences of mental health crises.
AB  - BACKGROUND: As Norway moves toward the provision of home-based crisis response,
      knowledge is needed about understandings of mental health crisis and effective
      ways of addressing crises within the home. OBJECTIVE: To elicit and learn from
      service users' experiences about the subjective meanings of crisis and what kind
      of help will be most effective in resolving mental health crises.  THEORETICAL: A
      phenomenological-hermeneutic cooperative inquiry method was used to elicit and
      analyse focus group responses from mental health service users who had
      experienced crises. RESULTS: FINDINGS CLUSTERED INTO THREE THEMES: (1) Crisis as
      multifaceted and varied experiences; (2) losing the skills and structure of
      everyday life; and (3) complexities involved in family support. CONCLUSION:
      Several aspects of crises require an expansion of the biomedical model of acute
      intervention to include consideration of the personal and familial meaning of the
      crisis, attention to the home context, and activities of daily living that are
      disrupted by the crisis, and ways for the person and the family to share in and
      learn from resolution of the crisis.

PMID- 22140399
TI  - Lack of evidence for prescription of antepartum bed rest.
AB  - Antepartum bed-rest treatment is based on assumptions that it is both effective
      and safe for mother and fetus. However, research indicates, that bed-rest
      treatment is ineffective for preventing preterm birth and fetal growth
      restriction, and for increasing gestational age at birth and infant birthweight.
      Studies of women treated with pregnancy bed-rest identify numerous side effects,
      including muscle atrophy, bone loss, weight loss, decreased infant birthweight in
      singleton gestations and gestational age at birth, and psychosocial problems.
      Studies conducted by aerospace scientists who have used bed rest as a model for
      the study of weightlessness in space using nonpregnant individuals report similar
      results. Antepartum bed-rest treatment should be discontinued until evidence of
      effectiveness is found.

PMID- 22140401
TI  - Affiliation Goals and Health Behaviors.
AB  - People are inherently driven by the need to form and maintain relationships, and
      these affiliation goals can influence health behaviors in two ways: (a)
      indirectly, by increasing a person's attention to others and subsequently leaving
      them more likely to emulate the health behaviors of others (social contagion);
      (b) directly, by leading people to be more likely to engage in health behaviors
      they perceive as helping them to form and maintain relationships with others
      (self-initiated behavioral engagement). In this review, we discuss the evidence
      for the catalyzing role of affiliation goals in these two processes for a variety
      of positive (e.g., exercising, smoking-cessation) and detrimental health
      behaviors (e.g., binge drinking and eating, needle sharing). Additionally, we
      discuss individual difference factors that may temporarily or chronically
      activate affiliation goals and ultimately impact health behaviors. Affiliation
      goals hold many implications for future work, and for improving interventions.

PMID- 22140402
TI  - Warfarin and calcific uremic arteriolopathy.

PMID- 22140404
TI  - A missed case of intra-abdominal sepsis.

PMID- 22140403
TI  - Septic polyarthritis caused by Streptococcus pneumoniae: primary pneumococcal
      pneumonia as a risk factor in older patients? A case report.
AB  - Septic polyarthritis associated to Streptococcus pneumoniae pneumonia is rarely
      seen and deserves description. In the present report, the case of a 77-year-old
      man with a 3-day clinical history of arthritis lacking anamnesis of trauma is
      discussed. Physical examination showed inflammatory signs and elevated
      inflammatory parameters in blood samples. The patient experienced pneumonia with
      blood cultures positive for S pneumoniae simultaneously. Arthrotomy revealed
      putride arthritis with S pneumoniae in culture. Therapy was initiated with
      intravenous benzylpenicillin. Surgical drainage and frequent retesting managed
      the local infection. Antibiotics had to be changed according to the specific
      sensitivity to ceftriaxone. Antimicrobial therapy was given intravenously for a
      total of 6 weeks.On follow-up no inflammatory signs were observed after 4 and 9
      months. A bistrategical approach with surgical drainage and frequent retesting
      and antimicrobial chemotherapy may lead to a good result in the treatment of
      pneumococcal septic arthritis.

PMID- 22140405
TI  - Duplicated middle cerebral artery.
AB  - Duplicated middle cerebral artery (DMCA) is an anomalous vessel arising from the
      internal carotid artery. The incidence DMCA is relatively law, and an association
      between this anomaly and cerebral aneurysms has been documented. There is a
      controversy whether DMCA may have perforating arteries. This is an important fact
      to consider in aneurysm surgery. We report the case of a 34-year-old black woman
      who suffered a subarachnoid hemorrhage and the angiography a left DMCA, and an
      aneurysm in an inferior branch of the main MCA. The DMCA and the MCA had
      perforating arteries. The aneurysm was clipped without complications. The
      observation of perforating arteries in our patient confirms that the DMCA may
      have perforating arteries. This is very important to be considered in cerebral
      aneurysms surgery. Moreover, the DMCA may potentially serve as a collateral blood
      supply to the MCA territory in cases of MCA occlusion.

PMID- 22140406
TI  - Transient rise in alkaline phosphatase activity in adults.
AB  - Benign transient hyperphosphatasia (BTH) is a condition that occurs mainly in
      infants and children and is characterised by a transient increase of serum
      alkaline phosphatase (ALP) activity up to several fold the adult upper reference
      limit (URL). The present report concerns BTH in 2 patients, aged 59 and 52 years
      old, who showed no evidence of bone or liver disease but had an increase in ALP
      activity up to 20-fold and 13-fold the adult URL, respectively. The diagnosis of
      BTH in the first case was made retrospectively, and after excluding liver and
      bone disease. However, in the second case the diagnosis was made early in the
      course of the disease, by performing an ALP isoenzyme electrophoresis test.
      Lengthy and extensive investigations were avoided in the second case. These cases
      highlight the occurrence of this condition in adulthood as well as in infancy and
      childhood.

PMID- 22140407
TI  - Ectopic submandibular thyroid tissue with a coexisting normally located
      multinodular goitre: case report and review of the literature.
AB  - The simultaneous finding of submandibular ectopic thyroid tissue and functional
      orthotopic thyroid gland is an extremely rare event. The present report describes
      the case of a woman presenting with a left submandibular mass, distant from a
      palpable multinodular goitre. Ultrasonography showed an ovoidal solid mass
      adjacent to the lower margin of the left submandibular gland. Cytological
      specimens showed colloid material and thyroid follicular cells with no malignant
      features. A preoperative CT scan demonstrated a very thin connection between the
      thyroid and the submandibular mass. The patient underwent total thyroidectomy and
      excision of the submandibular mass. The histopathological diagnosis of the
      thyroid tissue was multinodular goitre, and the submandibular mass was ectopic
      thyroid tissue showing a hyperplastic pattern. The main differential diagnosis of
      the submandibular mass was a metastasis from a well differentiated cancer. This
      case illustrates that an ectopic thyroid off the midline may not necessarily be a
      metastasis from a thyroid cancer.

PMID- 22140408
TI  - Total regression of extensive conjunctival intraepithelial neoplasia with
      superficial corneal invasion treated with topical mitomycin C 0.02%.
AB  - OBJECTIVE: To report complete resolution of extensive conjunctival
      intraepithelial neoplasia in a patient treated with topical mitomycin C. METHODS:
      Based on clinical examination, impression cytology was performed on the corneal
      conjunctival lesion. Management consisted of topical mitomycin 0.02%,
      administered four times a day for four 1-week cycles, with 1 week off between
      cycles. RESULTS: Complete resolution of the neoplasm was observed by slit lamp
      examination at 5 weeks of treatment, and histological resolution by 7 weeks of
      treatment. There were no complications due to the use of mitomycin. CONCLUSIONS:
      Topical mitomycin C 2 mg/ml (0.02%) may be a safe and effective treatment for
      conjunctival intraepithelial neoplasm prior to surgical removal.

PMID- 22140409
TI  - Corrosive gastritis: an extreme outcome.
AB  - Caustic substances, whether acid or alkali, cause a wide range of injuries to the
      digestive tract, from mild hyperaemia to extensive necrosis and perforation. We
      report the case of 40-year-old woman who presented 6 weeks after intentional
      ingestion of hydrochloric acid with abdominal pain and haematemesis. Gastroscopy
      showed a necrosed and ulcerated stomach with pyloric stricture. The third attempt
      at dilatation of the stricture caused perforation of the lesser curvature of the
      stomach requiring laparoscopic gastroduodenostomy. The approach to corrosive
      ingestion and its subsequent management is discussed.

PMID- 22140410
TI  - True precocious puberty with vision loss.
AB  - A 7-year-old boy presented with progressive vision loss and simultaneous
      development of precocious puberty. On evaluation he was found to have a solid
      cystic tumour in the sellar and suprasellar region. He underwent trans-sphenoidal
      resection of the tumour and histopathological examination revealed pilocytic
      astrocytoma. However, he later succumbed to postoperative sepsis.

PMID- 22140411
TI  - Gastrothorax following upper gastrointestinal tract endoscopy.
AB  - A 27-year-old man presented with vomiting and breathlessness for 1 day, 5 days
      after upper gastrointestinal tract endoscopy. On admission, the patient was
      breathless but not cyanosed; he had sinus tachycardia (heart rate 110 beats/min)
      and was normotensive (blood pressure 120/75 mm Hg). There were signs of
      mediastinal shift to the right. There were no breath sounds over the left side of
      the chest but normal breath sounds were heard to the right of the sternum. His
      chest x ray, CT scan of the chest and a barium meal study revealed gastrothorax.
      He was operated on and at surgery the stomach and ascending colon were found
      herniating into the chest through a posterolateral defect of the left
      hemidiaphragm. These were moved back to the abdomen and the diaphragmatic defect
      was closed. The patient made an uneventful recovery and remained well when seen
      in the clinic 2 months following surgery.

PMID- 22140412
TI  - The chicken or the egg story: which came first, epigastric hernia in a patient
      with huge urinary bladder stone.

PMID- 22140413
TI  - Pharmacological hyperprolactinaemia.
AB  - A middle-aged woman was referred under the 2-week urgent brain cancer initiative
      following the finding of a raised serum prolactin level. The patient had been
      taking metoclopramide on a daily basis to aid her symptoms of irritable bowel
      syndrome. The raised prolactin level had led to oligomenorrhoea prompting her
      general practitioner (GP) to check pituitary hormone levels.Metoclopramide is a
      potent dopamine antagonist and dopamine acts as the physiological inhibitor of
      prolactin synthesis. Thus, the dopamine antagonism led to elevated prolactin
      level and the symptom of oligomenorrhoea.Following curtailment of the
      metoclopramide, the prolactin level normalised very quickly and the patient was
      reassured.Consideration should be given to non-pathological causes of
      hyperprolactinaemia, including physiological states such as pregnancy and
      concurrent medication.

PMID- 22140414
TI  - The brain in chronic pain: clinical implications.
AB  - This article examines the present, and potential future, impact of brain imaging
      on chronic pain. It is argued that novel theories of chronic pain are coming to
      the fore, specifically through brain imaging of the human brain in chronic pain.
      Such studies show that the brain reorganizes in relation to chronic pain, in a
      pattern specific to the type of clinical pain, and that brain networks and
      receptor targets are being identified and reverse translated to animal studies of
      their efficacy and mechanisms. Future studies need to integrate across human
      brain imaging techniques, as well as more intensive reverse translational
      methods.

PMID- 22140415
TI  - The evolving role of F-FDG PET scans in patients with aggressive non-Hodgkin's
      lymphoma.
AB  - Functional imaging by (18)F-fluorodeoxyglucose positron emission tomography
      ((18)F-FDG PET) is being increasingly incorporated into the evaluation of
      patients with aggressive non-Hodgkin lymphoma (NHL). Its use for the initial
      staging in combination with computed tomography has now become standard. PET has
      recently been included in consensus criteria for response after therapy for
      Hodgkin lymphoma and aggressive NHL. At the end of therapy, PET has a high
      positive and negative predictive value (PPV, NPV) for relapse in the pre
      rituximab era. However, in the rituximab era, there appears to be a higher rate
      of false-positive PET scans, making the PPV lower, while the NPV remains high.
      Interim PET scans are an attractive concept for early evaluation of response, and
      possibly to guide intensification or de-escalation of therapy. Similar to the end
      of-therapy scans, the PPV for mid-therapy scans appears to be low in the
      rituximab era. Trials testing the modification of therapy based on an interim PET
      scan are ongoing. For surveillance of patients in remission from aggressive NHL,
      there is as yet no convincing data that monitoring with PET is superior to
      traditional surveillance. The evidence to date suggests that a positive PET scan
      during or after rituximab-based therapy for aggressive NHL should be confirmed by
      a biopsy if major treatment decisions will be made using the results.

PMID- 22140416
TI  - Opportunities and challenges in omics.

PMID- 22140417
TI  - Proteomic Protease Substrate Profiling of tPA Treatment in Acute Ischemic Stroke
      Patients: A Step Toward Individualizing Thrombolytic Therapy at the Bedside.
AB  - Tissue plasminogen activator (tPA) is the only FDA-approved medical therapy for
      acute ischemic stroke. But as a serine peptidase, intravenous tPA can affect the
      expression of other proteases that may be implicated in blood-brain barrier
      breakdown. Such parallel cascades of cell signaling may be involved in
      intracranial hemorrhage, the major side effect of tPA. Here, we describe an
      initial attempt in proteomic substrate profiling, i.e., degradomics in human
      plasma within the context of acute stroke. Plasma from acute stroke patients were
      analyzed pre- and post-intravenous tPA using tandem mass spectrometry and protein
      array profiling to identify substrates and proteases of interest. In non-tPA
      treated stroke plasma, degradomic patterns indicated a rapid induction of
      protease activity within 3 h of stroke onset that mostly stabilized by 24 h. But
      in tPA-treated patients, pre- and post-tPA samples from the same patient
      demonstrated distinct degradomic patterns that persisted even up to 3-5 days
      after stroke onset. Matching control patients without strokes had little change
      in degradomic profiles over time. Our findings demonstrate that tPA treatment
      changes the plasma degradomic profiles in acute stroke patients. These composite
      proteolytic profiles may provide a glimpse of the pleiotropic effects of tPA on
      cellular signaling cascades at the bedside. This study supports the feasibility
      of performing pharmaco-proteomics at the bedside, which may ultimately allow us
      to dissect mechanisms of thrombolysis-related therapeutic efficacy in stroke. 

PMID- 22140419
TI  - BLOCK-BASED BAYESIAN EPISTASIS ASSOCIATION MAPPING WITH APPLICATION TO WTCCC TYPE
      1 DIABETES DATA.
AB  - Interactions among multiple genes across the genome may contribute to the risks
      of many complex human diseases. Whole-genome single nucleotide polymorphisms
      (SNPs) data collected for many thousands of SNP markers from thousands of
      individuals under the case-control design promise to shed light on our
      understanding of such interactions. However, nearby SNPs are highly correlated
      due to linkage disequilibrium (LD) and the number of possible interactions is too
      large for exhaustive evaluation. We propose a novel Bayesian method for
      simultaneously partitioning SNPs into LD-blocks and selecting SNPs within blocks
      that are associated with the disease, either individually or interactively with
      other SNPs. When applied to homogeneous population data, the method gives
      posterior probabilities for LD-block boundaries, which not only result in
      accurate block partitions of SNPs, but also provide measures of partition
      uncertainty. When applied to case-control data for association mapping, the
      method implicitly filters out SNP associations created merely by LD with disease
      loci within the same blocks. Simulation study showed that this approach is more
      powerful in detecting multi-locus associations than other methods we tested,
      including one of ours. When applied to the WTCCC type 1 diabetes data, the method
      identified many previously known T1D associated genes, including PTPN22, CTLA4,
      MHC, and IL2RA. The method also revealed some interesting two-way associations
      that are undetected by single SNP methods. Most of the significant associations
      are located within the MHC region. Our analysis showed that the MHC SNPs form
      long-distance joint associations over several known recombination hotspots. By
      controlling the haplotypes of the MHC class II region, we identified additional
      associations in both MHC class I (HLA-A, HLA-B) and class III regions (BAT1). We
      also observed significant interactions between genes PRSS16, ZNF184 in the
      extended MHC region and the MHC class II genes. The proposed method can be
      broadly applied to the classification problem with correlated discrete
      covariates.

PMID- 22140418
TI  - Non-template functions of viral RNA in picornavirus replication.
AB  - The genomic RNA of poliovirus and closely related picornaviruses perform template
      and non-template functions during viral RNA replication. The non-template
      functions are mediated by cis-active RNA sequences that bind viral and cellular
      proteins to form RNP complexes. The RNP complexes mediate temporally dynamic,
      long-range interactions in the viral genome and ensure the specificity of
      replication. The 5' cloverleaf (5' CL)-RNP complex serves as a key cis-active
      element in all of the non-template functions of viral RNA. The 5'CL-RNP complex
      is proposed to interact with the cre-RNP complex during VPgpUpU synthesis, the
      3'NTR-poly(A) RNP complex during negative-strand initiation and the 30 end
      negative-strand-RNP complex during positive-strand initiation. Co-ordinating
      these long-range interactions is important in regulating each step in the
      replication cycle.

PMID- 22140423
TI  - Clonal relatedness of enterotoxigenic Escherichia coli (ETEC) strains expressing
      LT and CS17 isolated from children with diarrhoea in La Paz, Bolivia.
AB  - BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a major cause of
      traveller's and infantile diarrhoea in the developing world. ETEC produces two
      toxins, a heat-stable toxin (known as ST) and a heat-labile toxin (LT) and
      colonization factors that help the bacteria to attach to epithelial cells.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we characterized a subset of ETEC
      clinical isolates recovered from Bolivian children under 5 years of age using a
      combination of multilocus sequence typing (MLST) analysis, virulence typing,
      serotyping and antimicrobial resistance test patterns in order to determine the
      genetic background of ETEC strains circulating in Bolivia. We found that strains
      expressing the heat-labile (LT) enterotoxin and colonization factor CS17 were
      common and belonged to several MLST sequence types but mainly to sequence type
      423 and sequence type-443 (Achtman scheme). To further study the LT/CS17 strains
      we analysed the nucleotide sequence of the CS17 operon and compared the structure
      to LT/CS17 ETEC isolates from Bangladesh. Sequence analysis confirmed that all
      sequence type-423 strains from Bolivia had a single nucleotide polymorphism;
      SNP(bol) in the CS17 operon that was also found in some other MLST sequence types
      from Bolivia but not in strains recovered from Bangladeshi children. The dominant
      ETEC clone in Bolivia (sequence type-423/SNP(bol)) was found to persist over
      multiple years and was associated with severe diarrhoea but these strains were
      variable with respect to antimicrobial resistance patterns.
      CONCLUSION/SIGNIFICANCE: The results showed that although the LT/CS17 phenotype
      is common among ETEC strains in Bolivia, multiple clones, as determined by unique
      MLST sequence types, populate this phenotype. Our data also appear to suggest
      that acquisition and loss of antimicrobial resistance in LT-expressing CS17 ETEC
      clones is more dynamic than acquisition or loss of virulence factors.

PMID- 22140424
TI  - Establishing long-term efficacy in chronic disease: use of recursive partitioning
      and propensity score adjustment to estimate outcome in MS.
AB  - CONTEXT: Establishing the long-term benefit of therapy in chronic diseases has
      been challenging. Long-term studies require non-randomized designs and, thus, are
      often confounded by biases. For example, although disease-modifying therapy in MS
      has a convincing benefit on several short-term outcome-measures in randomized
      trials, its impact on long-term function remains uncertain. OBJECTIVE: Data from
      the 16-year Long-Term Follow-up study of interferon-beta-1b is used to assess the
      relationship between drug-exposure and long-term disability in MS patients.
      DESIGN/SETTING: To mitigate the bias of outcome-dependent exposure variation in
      non-randomized long-term studies, drug-exposure was measured as the medication
      possession-ratio, adjusted up or down according to multiple different weighting
      schemes based on MS severity and MS duration at treatment initiation. A recursive
      partitioning algorithm assessed whether exposure (using any weighing scheme)
      affected long-term outcome. The optimal cut-point that was used to define "high"
      or "low" exposure-groups was chosen by the algorithm. Subsequent to verification
      of an exposure-impact that included all predictor variables, the two groups were
      compared using a weighted propensity-stratified analysis in order to mitigate any
      treatment-selection bias that may have been present. Finally, multiple
      sensitivity-analyses were undertaken using different definitions of long-term
      outcome and different assumptions about the data. MAIN OUTCOME MEASURE: Long-Term
      Disability. RESULTS: In these analyses, the same weighting-scheme was
      consistently selected by the recursive-partitioning algorithm. This scheme
      reduced (down-weighted) the effectiveness of drug exposure as either disease
      duration or disability at treatment-onset increased. Applying this scheme and
      using propensity-stratification to further mitigate bias, high-exposure had a
      consistently better clinical outcome compared to low-exposure (Cox proportional
      hazard ratio = 0.30-0.42; p<0.0001). CONCLUSIONS: Early initiation and sustained
      use of interferon-beta-1b has a beneficial impact on long-term outcome in MS. Our
      analysis strategy provides a methodological framework for bias-mitigation in the
      analysis of non-randomized clinical data. TRIAL REGISTRATION:
      Clinicaltrials.govNCT00206635.

PMID- 22140425
TI  - Targeting acetylcholinesterase: identification of chemical leads by high
      throughput screening, structure determination and molecular modeling.
AB  - Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic
      transmission by rapid hydrolysis of the neurotransmitter acetylcholine. Compounds
      inhibiting this enzyme can be used (inter alia) to treat cholinergic deficiencies
      (e.g. in Alzheimer's disease), but may also act as dangerous toxins (e.g. nerve
      agents such as sarin). Treatment of nerve agent poisoning involves use of
      antidotes, small molecules capable of reactivating AChE. We have screened a
      collection of organic molecules to assess their ability to inhibit the enzymatic
      activity of AChE, aiming to find lead compounds for further optimization leading
      to drugs with increased efficacy and/or decreased side effects. 124 inhibitors
      were discovered, with considerable chemical diversity regarding size, polarity,
      flexibility and charge distribution. An extensive structure determination
      campaign resulted in a set of crystal structures of protein-ligand complexes.
      Overall, the ligands have substantial interactions with the peripheral anionic
      site of AChE, and the majority form additional interactions with the catalytic
      site (CAS). Reproduction of the bioactive conformation of six of the ligands
      using molecular docking simulations required modification of the default
      parameter settings of the docking software. The results show that docking
      assisted structure-based design of AChE inhibitors is challenging and requires
      crystallographic support to obtain reliable results, at least with currently
      available software. The complex formed between C5685 and Mus musculus AChE
      (C5685*mAChE) is a representative structure for the general binding mode of the
      determined structures. The CAS binding part of C5685 could not be structurally
      determined due to a disordered electron density map and the developed docking
      protocol was used to predict the binding modes of this part of the molecule. We
      believe that chemical modifications of our discovered inhibitors, biochemical and
      biophysical characterization, crystallography and computational chemistry provide
      a route to novel AChE inhibitors and reactivators.

PMID- 22140426
TI  - Dancing for food in the deep sea: bacterial farming by a new species of Yeti
      crab.
AB  - Vent and seep animals harness chemosynthetic energy to thrive far from the sun's
      energy. While symbiont-derived energy fuels many taxa, vent crustaceans have
      remained an enigma; these shrimps, crabs, and barnacles possess a
      phylogenetically distinct group of chemosynthetic bacterial epibionts, yet the
      role of these bacteria has remained unclear. We test whether a new species of
      Yeti crab, which we describe as Kiwa puravida n. sp, farms the epibiotic bacteria
      that it grows on its chelipeds (claws), chelipeds that the crab waves in fluid
      escaping from a deep-sea methane seep. Lipid and isotope analyses provide
      evidence that epibiotic bacteria are the crab's main food source and K. puravida
      n. sp. has highly-modified setae (hairs) on its 3(rd) maxilliped (a mouth
      appendage) which it uses to harvest these bacteria. The epsilon- and gamma-
      proteobacteria that this methane-seep species farms are closely related to
      hydrothermal-vent decapod epibionts. We hypothesize that this species waves its
      arm in reducing fluid to increase the productivity of its epibionts by removing
      boundary layers which may otherwise limit carbon fixation. The discovery of this
      new species, only the second within a family described in 2005, stresses how much
      remains undiscovered on our continental margins.

PMID- 22140427
TI  - Podargiform affinities of the enigmatic Fluvioviridavis platyrhamphus and the
      early diversification of Strisores ("Caprimulgiformes" + Apodiformes).
AB  - BACKGROUND: The early Eocene Green River Formation avifauna preserves exceptional
      exemplars of the earliest unambiguous stem representatives of many extant avian
      clades. We identify the basal-most member of Podargiformes (extant and fossil
      stem lineage frogmouths) based on a new specimen of Fluvioviridavis
      platyrhamphus, a unique neoavian bird from the Fossil Butte Member of the Green
      River Formation of Wyoming. Extant frogmouths (Podargidae) comprise approximately
      13 nocturnal species with an exclusively Australasian distribution.
      METHODOLOGY/PRINCIPAL FINDINGS: The new specimen was included in a combined
      phylogenetic analysis of morphological (osteology and soft tissue) and molecular
      sequence (cytochrome b, c-myc exon 3, and RAG) data sampling species-level taxa
      from both extant and extinct members of Steatornithidae, Podargidae,
      Caprimulgidae, Nyctibiidae, Aegothelidae, and Apodiformes ( = Strisores). New
      data from F. platyrhamphus help resolve phylogenetic relationships within
      Strisores, supporting placement of F. platyrhamphus and the European fossil form
      Masillapodargus longipes as basal parts of Podargiformes and also supporting a
      sister taxon relationship between Podargiformes and Steatornithiformes (oilbirds)
      within Strisores. This relationship is recovered only when fossil taxa are
      included, reaffirming the potential impact of stem fossil taxa on inferences of
      phylogenetic relationships. The well-preserved mandible and palate of the new
      specimen demonstrate that many of the unique characteristics of the skull that
      characterize the crown frogmouth clade Podargidae arose early in the evolutionary
      history of the clade, over 50 million years ago. Comparisons with the new
      specimen also indicate that Eurofluvioviridavis and Fluvioviridavis are not
      closely related. CONCLUSIONS/SIGNIFICANCE: Together with the European fossil
      frogmouth Masillapodargus, Fluvioviridavis shows that Podargiformes had a much
      wider geographic distribution in the past, whereas extant species are restricted
      to Australasia. The Eocene record of Strisores from the Green River Formation and
      Messel Formation indicates most major subclade divergences had already occurred
      by the early-middle Eocene.

PMID- 22140428
TI  - Quantitative high-resolution genomic analysis of single cancer cells.
AB  - During cancer progression, specific genomic aberrations arise that can determine
      the scope of the disease and can be used as predictive or prognostic markers. The
      detection of specific gene amplifications or deletions in single blood-borne or
      disseminated tumour cells that may give rise to the development of metastases is
      of great clinical interest but technically challenging. In this study, we present
      a method for quantitative high-resolution genomic analysis of single cells. Cells
      were isolated under permanent microscopic control followed by high-fidelity whole
      genome amplification and subsequent analyses by fine tiling array-CGH and qPCR.
      The assay was applied to single breast cancer cells to analyze the chromosomal
      region centred by the therapeutical relevant EGFR gene. This method allows
      precise quantitative analysis of copy number variations in single cell
      diagnostics.

PMID- 22140429
TI  - Golgi apparatus-localized synaptotagmin 2 is required for unconventional
      secretion in Arabidopsis.
AB  - BACKGROUND: Most secretory proteins contain signal peptides that direct their
      sorting to the ER and secreted via the conventional ER/Golgi transport pathway,
      while some signal-peptide-lacking proteins have been shown to export through
      ER/Golgi independent secretory pathways. Hygromycin B is an aminoglycoside
      antibiotic produced by Streptomyces hygroscopicus that is active against both
      prokaryotic and eukaryotic cells. The hygromycin phosphotransferase (HYG(R)) can
      phosphorylate and inactivate the hygromycin B, and has been widely used as a
      positive selective marker in the construction of transgenic plants. However, the
      localization and trafficking of HYG(R) in plant cells remain unknown.
      Synaptotagmins (SYTs) are involved in controlling vesicle endocytosis and
      exocytosis as calcium sensors in animal cells, while their functions in plant
      cells are largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: We found Arabidopsis
      synaptotagmin SYT2 was localized on the Golgi apparatus by immunofluorescence and
      immunogold labeling. Surprisingly, co-expression of SYT2 and HYG(R) caused
      hypersensitivity of the transgenic Arabidopsis plants to hygromycin B. HYG(R),
      which lacks a signal sequence, was present in the cytoplasm as well as in the
      extracellular space in HYG(R)-GFP transgenic Arabidopsis plants and its secretion
      is not sensitive to brefeldin A treatment, suggesting it is not secreted via the
      conventional secretory pathway. Furthermore, we found that HYG(R)-GFP was
      truncated at carboxyl terminus of HYG(R) shortly after its synthesis, and the
      cells deficient SYT2 failed to efficiently truncate HYG(R)-GFP,resulting in
      HYG(R)-GFP accumulated in prevacuoles/vacuoles, indicating that SYT2 was involved
      in HYG(R)-GFP trafficking and secretion. CONCLUSION/SIGNIFICANCE: These findings
      reveal for the first time that SYT2 is localized on the Golgi apparatus and
      regulates HYG(R)-GFP secretion via the unconventional protein transport from the
      cytosol to the extracelluar matrix in plant cells.

PMID- 22140430
TI  - Inhibition of Rho kinase regulates specification of early differentiation events
      in P19 embryonal carcinoma stem cells.
AB  - BACKGROUND: The Rho kinase pathway plays a key role in many early cell/tissue
      determination events that take place in embryogenesis. Rho and its downstream
      effector Rho kinase (ROCK) play pivotal roles in cell migration, apoptosis
      (membrane blebbing), cell proliferation/cell cycle, cell-cell adhesion and gene
      regulation. We and others have previously demonstrated that inhibition of ROCK
      blocks endoderm differentiation in embryonal carcinoma stem cells, however, the
      effect of ROCK inhibition on mesoderm and ectoderm specification has not been
      fully examined. In this study, the role of ROCK within the specification and
      differentiation of all three germ layers was examined. METHODOLOGY/PRINCIPAL
      FINDINGS: P19 cells were treated with the specific ROCK inhibitor Y-27623, and
      increase in differentiation efficiency into neuro-ectodermal and mesodermal
      lineages was observed. However, as expected a dramatic decrease in early
      endodermal markers was observed when ROCK was inhibited. Interestingly, within
      these ROCK-inhibited RA treated cultures, increased levels of mesodermal or
      ectodermal markers were not observed, instead it was found that the pluripotent
      markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in
      undifferentiated cultures. Using standard and widely accepted methods for
      reproducible P19 differentiation into all three germ layers, an enhancement of
      mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage
      specification was observed with Y-27632 treatment. Evidence would suggest that
      this effect is in part mediated through TGF-beta and SMAD signaling as ROCK
      inhibited cells displayed aberrant SMAD activation and did not return to a
      'ground' state after the inhibition had been removed. CONCLUSIONS/SIGNIFICANCE:
      Given this data and the fact that only a partial rescue of normal differentiation
      capacity occurred when ROCK inhibition was alleviated, the effect of ROCK
      inhibition on the differentiation capacity of pluripotent cell populations should
      be further examined to elucidate the role of the Rho-ROCK pathway in early
      cellular 'fate' decision making processes.

PMID- 22140431
TI  - Generation and characterization of rat and mouse monoclonal antibodies specific
      for MeCP2 and their use in X-inactivation studies.
AB  - Methyl CpG binding protein 2 (MeCP2) binds DNA, and has a preference for
      methylated CpGs and, hence, in cells, it accumulates in heterochromatin. Even
      though it is expressed ubiquitously MeCP2 is particularly important during
      neuronal maturation. This is underscored by the fact that in Rett syndrome, a
      neurological disease, 80% of patients carry a mutation in the MECP2 gene. Since
      the MECP2 gene lies on the X chromosome and is subjected to X chromosome
      inactivation, affected patients are usually chimeric for wild type and mutant
      MeCP2. Here, we present the generation and characterization of the first rat
      monoclonal MeCP2 specific antibodies as well as mouse monoclonal antibodies and a
      rabbit polyclonal antibody. We demonstrate that our antibodies are suitable for
      immunoblotting, (chromatin) immunoprecipitation and immunofluorescence of
      endogenous and ectopically expressed MeCP2. Epitope mapping revealed that most of
      the MeCP2 monoclonal antibodies recognize the C-terminal domain and one the N
      terminal domain of MeCP2. Using slot blot analysis, we determined a high
      sensitivity of all antibodies, detecting amounts as low as 1 ng of MeCP2 protein.
      Moreover, the antibodies recognize MeCP2 from different species, including human,
      mouse, rat and pig. Lastly, we have validated their use by analyzing and
      quantifying X chromosome inactivation skewing using brain tissue of MeCP2
      heterozygous null female mice. The new MeCP2 specific monoclonal antibodies
      described here perform well in a large variety of immunological applications
      making them a very valuable set of tools for studies of MeCP2 pathophysiology in
      situ and in vitro.

PMID- 22140432
TI  - Contrasting ecosystem-effects of morphologically similar copepods.
AB  - Organisms alter the biotic and abiotic conditions of ecosystems. They can
      modulate the availability of resources to other species (ecosystem engineering)
      and shape selection pressures on other organisms (niche construction). Very
      little is known about how the engineering effects of organisms vary among and
      within species, and, as a result, the ecosystem consequences of species
      diversification and phenotypic evolution are poorly understood. Here, using a
      common gardening experiment, we test whether morphologically similar species and
      populations of Diaptomidae copepods (Leptodiaptomus ashlandi, Hesperodiaptomus
      franciscanus, Skistodiaptomus oregonensis) have similar or different effects on
      the structure and function of freshwater ecosystems. We found that copepod
      species had contrasting effects on algal biomass, ammonium concentrations, and
      sedimentation rates, and that copepod populations had contrasting effects on
      prokaryote abundance, sedimentation rates, and gross primary productivity. The
      average size of ecosystem-effect contrasts between species was similar to those
      between populations, and was comparable to those between fish species and
      populations measured in previous common gardening experiments. Our results
      suggest that subtle morphological variation among and within species can cause
      multifarious and divergent ecosystem-effects. We conclude that using
      morphological trait variation to assess the functional similarity of organisms
      may underestimate the importance of species and population diversity for
      ecosystem functioning.

PMID- 22140433
TI  - Screening of peptide libraries against protective antigen of Bacillus anthracis
      in a disposable microfluidic cartridge.
AB  - Bacterial surface peptide display has gained popularity as a method of affinity
      reagent generation for a wide variety of applications ranging from drug discovery
      to pathogen detection. In order to isolate the bacterial clones that express
      peptides with high affinities to the target molecule, multiple rounds of manual
      magnetic activated cell sorting (MACS) followed by multiple rounds of
      fluorescence activated cell sorting (FACS) are conventionally used. Although such
      manual methods are effective, alternative means of library screening which
      improve the reproducibility, reduce the cost, reduce cross contamination, and
      minimize exposure to hazardous target materials are highly desired for practical
      application. Toward this end, we report the first semi-automated system
      demonstrating the potential for screening bacterially displayed peptides using
      disposable microfluidic cartridges. The Micro-Magnetic Separation platform (MMS)
      is capable of screening a bacterial library containing 3 * 1010 members in 15
      minutes and requires minimal operator training. Using this system, we report the
      isolation of twenty-four distinct peptide ligands that bind to the protective
      antigen (PA) of Bacilus anthracis in three rounds of selection. A consensus motif
      WXCFTC was found using the MMS and was also found in one of the PA binders
      isolated by the conventional MACS/FACS approach. We compared MMS and MACS rare
      cell recovery over cell populations ranging from 0.1% to 0.0000001% and found
      that both magnetic sorting methods could recover cells down to 0.0000001% initial
      cell population, with the MMS having overall lower standard deviation of cell
      recovery. We believe the MMS system offers a compelling approach towards highly
      efficient, semi-automated screening of molecular libraries that is at least equal
      to manual magnetic sorting methods and produced, for the first time, 15-mer
      peptide binders to PA protein that exhibit better affinity and specificity than
      peptides isolated using conventional MACS/FACS.

PMID- 22140434
TI  - Platelet and neutrophil responses to Gram positive pathogens in patients with
      bacteremic infection.
AB  - BACKGROUND: Many Gram-positive pathogens aggregate and activate platelets in
      vitro and this has been proposed to contribute to virulence. Platelets can also
      form complexes with neutrophils but little is however known about platelet and
      platelet-neutrophil responses in bacterial infection. METHODOLOGY/PRINCIPAL
      FINDINGS: We added isolates of Gram-positive bacteria from 38 patients with a
      bacteremic infection to blood drawn from the same patient. Aggregometry and flow
      cytometry were used to assess platelet aggregation and to quantify activation of
      platelets, neutrophils, and platelet-neutrophils complexes (PNCs) induced by the
      bacteria. Fifteen healthy persons served as controls. Most isolates of
      Staphylococcus aureus, beta hemolytic streptococci, and Enterococcus faecalis
      induced aggregation of platelets from their respective hosts, whereas pneumococci
      failed to do so. S. aureus isolates induced platelet aggregation more rapidly in
      patients than in controls, whereas platelet activation by S. aureus was lower in
      patients than in controls. PNCs were more abundant in baseline samples from
      patients than in healthy controls and most bacterial isolates induced additional
      PNC formation and neutrophil activation. CONCLUSION/SIGNIFICANCE: We have
      demonstrated for the first time that bacteria isolated from patients with Gram
      positive bacteremia can induce platelet activation and aggregation, PNC
      formation, and neutrophil activation in the same infected host. This underlines
      the significance of these interactions during infection, which could be a target
      for future therapies in sepsis.

PMID- 22140435
TI  - Constitutive versus responsive gene expression strategies for growth in changing
      environments.
AB  - Microbes respond to changing environments by adjusting gene expression levels to
      the demand for the corresponding proteins. Adjusting protein levels is slow,
      consequently cells may reach the optimal protein level only by a time when the
      demand changed again. It is therefore not a priori clear whether expression "on
      demand" is always the optimal strategy. Indeed, many genes are constitutively
      expressed at intermediate levels, which represents a permanent cost but provides
      an immediate benefit when the protein is needed. Which are the conditions that
      select for a responsive or a constitutive expression strategy, what determines
      the optimal constitutive expression level in a changing environment, and how is
      the fitness of the two strategies affected by gene expression noise? Based on an
      established model of the lac- and gal-operon expression dynamics, we study the
      fitness of a constitutive and a responsive expression strategy in time-varying
      environments. We find that the optimal constitutive expression level differs from
      the average demand for the gene product and from the average optimal expression
      level; depending on the shape of the growth rate function, the optimal expression
      level either provides intermediate fitness in all environments, or maximizes
      fitness in only one of them. We find that constitutive expression can provide
      higher fitness than responsive expression even when regulatory machinery comes at
      no cost, and we determine the minimal response rate necessary for "expression on
      demand" to confer a benefit. Environmental and inter-cellular noise favor the
      responsive strategy while reducing fitness of the constitutive one. Our results
      show the interplay between the demand-frequency for a gene product, the genetic
      response rate, and the fitness, and address important questions on the evolution
      of gene regulation. Some of our predictions agree with recent yeast high
      throughput data, for others we propose the experiments that are needed to verify
      them.

PMID- 22140436
TI  - High fat diet-induced changes in mouse muscle mitochondrial phospholipids do not
      impair mitochondrial respiration despite insulin resistance.
AB  - BACKGROUND: Type 2 diabetes mellitus and muscle insulin resistance have been
      associated with reduced capacity of skeletal muscle mitochondria, possibly as a
      result of increased intake of dietary fat. Here, we examined the hypothesis that
      a prolonged high-fat diet consumption (HFD) increases the saturation of muscle
      mitochondrial membrane phospholipids causing impaired mitochondrial oxidative
      capacity and possibly insulin resistance. METHODOLOGY: C57BL/6J mice were fed an
      8-week or 20-week low fat diet (10 kcal%; LFD) or HFD (45 kcal%). Skeletal muscle
      mitochondria were isolated and fatty acid (FA) composition of skeletal muscle
      mitochondrial phospholipids was analyzed by thin-layer chromatography followed by
      GC. High-resolution respirometry was used to assess oxidation of pyruvate and
      fatty acids by mitochondria. Insulin sensitivity was estimated by HOMA-IR.
      PRINCIPAL FINDINGS: At 8 weeks, mono-unsaturated FA (16?1n7, 18?1n7 and 18?1n9)
      were decreased (-4.0%, p<0.001), whereas saturated FA (16?0) were increased
      (+3.2%, p<0.001) in phospholipids of HFD vs. LFD mitochondria. Interestingly, 20
      weeks of HFD descreased mono-unsaturated FA while n-6 poly-unsaturated FA
      (18?2n6, 20?4n6, 22?5n6) showed a pronounced increase (+4.0%, p<0.001). Despite
      increased saturation of muscle mitochondrial phospholipids after the 8-week HFD,
      mitochondrial oxidation of both pyruvate and fatty acids were similar between LFD
      and HFD mice. After 20 weeks of HFD, the increase in n-6 poly-unsaturated FA was
      accompanied by enhanced maximal capacity of the electron transport chain (+49%, p
      = 0.002) and a tendency for increased ADP-stimulated respiration, but only when
      fuelled by a lipid-derived substrate. Insulin sensitivity in HFD mice was reduced
      at both 8 and 20 weeks. CONCLUSIONS/INTERPRETATION: Our findings do not support
      the concept that prolonged HF feeding leads to increased saturation of skeletal
      muscle mitochondrial phospholipids resulting in a decrease in mitochondrial fat
      oxidative capacity and (muscle) insulin resistance.

PMID- 22140437
TI  - Evolutionary relationships of microbial aromatic prenyltransferases.
AB  - The linkage of isoprenoid and aromatic moieties, catalyzed by aromatic
      prenyltransferases (PTases), leads to an impressive diversity of primary and
      secondary metabolites, including important pharmaceuticals and toxins. A few
      years ago, a hydroxynaphthalene PTase, NphB, featuring a novel ten-stranded beta
      barrel fold was identified in Streptomyces sp. strain CL190. This fold, termed
      the PT-barrel, is formed of five tandem alphaalphabetabeta structural repeats and
      remained exclusive to the NphB family until its recent discovery in the DMATS
      family of indole PTases. Members of these two families exist only in fungi and
      bacteria, and all of them appear to catalyze the prenylation of aromatic
      substrates involved in secondary metabolism. Sequence comparisons using PSI-BLAST
      do not yield matches between these two families, suggesting that they may have
      converged upon the same fold independently. However, we now provide evidence for
      a common ancestry for the NphB and DMATS families of PTases. We also identify
      sequence repeats that coincide with the structural repeats in proteins belonging
      to these two families. Therefore we propose that the PT-barrel arose by
      amplification of an ancestral alphaalphabetabeta module. In view of their
      homology and their similarities in structure and function, we propose to group
      the NphB and DMATS families together into a single superfamily, the PT-barrel
      superfamily.

PMID- 22140438
TI  - TmDOTA-tetraglycinate encapsulated liposomes as pH-sensitive LipoCEST agents.
AB  - Lanthanide DOTA-tetraglycinate (LnDOTA-(gly)4-) complexes contain four
      magnetically equivalent amide protons that exchange with protons of bulk water.
      The rate of this base catalyzed exchange process has been measured using chemical
      exchange saturation transfer (CEST) NMR techniques as a function of solution pH
      for various paramagnetic LnDOTA-(gly)4- complexes to evaluate the effects of
      lanthanide ion size on this process. Complexes with Tb(III), Dy(III), Tm(III) and
      Yb(III) were chosen because these ions induce large hyperfine shifts in all
      ligand protons, including the exchanging amide protons. The magnitude of the
      amide proton CEST exchange signal differed for the four paramagnetic complexes in
      order, Yb>Tm>Tb>Dy. Although the Dy(III) complex showed the largest hyperfine
      shift as expected, the combination of favorable chemical shift and amide proton
      CEST linewidth in the Tm(III) complex was deemed most favorable for future in
      vivo applications where tissue magnetization effects can interfere. TmDOTA-(gly)4
      at various concentrations was encapsulated in the core interior of liposomes to
      yield lipoCEST particles for molecular imaging. The resulting nanoparticles
      showed less than 1% leakage of the agent from the interior over a range of
      temperatures and pH. The pH versus amide proton CEST curves differed for the free
      versus encapsulated agents over the acidic pH regions, consistent with a lower
      proton permeability across the liposomal bilayer for the encapsulated agent.
      Nevertheless, the resulting lipoCEST nanoparticles amplify the CEST sensitivity
      by a factor of ~104 compared to the free, un-encapsulated agent. Such pH
      sensitive nano-probes could prove useful for pH mapping of liposomes targeted to
      tumors.

PMID- 22140439
TI  - Estimating the burden of tuberculosis among foreign-born persons acquired prior
      to entering the U.S., 2005-2009.
AB  - BACKGROUND: The true burden of reactivation of remote latent tuberculosis
      infection (reactivation TB) among foreign-born persons with tuberculosis (TB)
      within the United States is not known. Our study objectives were to estimate the
      proportion of foreign-born persons with TB due reactivation TB and to describe
      characteristics of foreign-born persons with reactivation TB. METHODS: We
      conducted a cross-sectional study of patients with an M. tuberculosis isolate
      genotyped by the U.S. National TB Genotyping Service, 2005-2009. TB cases were
      attributed to reactivation TB if they were not a member of a localized cluster of
      cases. Localized clusters were determined by a spatial scan statistic of cases
      with isolates with matching TB genotype results. Crude odds ratios and 95%
      confidence intervals were used to assess relations between reactivation TB and
      select factors among foreign-born persons. MAIN RESULTS: Among the 36,860 cases
      with genotyping and surveillance data reported, 22,151 (60%) were foreign-born.
      Among foreign-born persons with TB, 18,540 (83.7%) were attributed to
      reactivation TB. Reactivation TB among foreign-born persons was associated with
      increasing age at arrival, incidence of TB in the country of origin, and
      decreased time in the U.S. at the time of TB diagnosis. CONCLUSIONS: Four out of
      five TB cases among foreign-born persons can be attributed to reactivation TB and
      present the largest challenge to TB elimination in the U.S. TB control strategies
      among foreign-born persons should focus on finding and treating latent
      tuberculosis infection prior to or shortly after arrival to the United States and
      on reducing the burden of LTBI through improvements in global TB control.

PMID- 22140440
TI  - Specific alterations in complement protein activity of little brown myotis
      (Myotis lucifugus) hibernating in white-nose syndrome affected sites.
AB  - White-nose syndrome (WNS) is the most devastating condition ever reported for
      hibernating bats, causing widespread mortality in the northeastern United States.
      The syndrome is characterized by cutaneous lesions caused by a recently
      identified psychrophilic and keratinophylic fungus (Geomyces destructans),
      depleted fat reserves, atypical behavior, and damage to wings; however, the
      proximate cause of mortality is still uncertain. To assess relative levels of
      immunocompetence in bats hibernating in WNS-affected sites compared with levels
      in unaffected bats, we describe blood plasma complement protein activity in
      hibernating little brown myotis (Myotis lucifugus) based on microbicidal
      competence assays using Escherichia coli, Staphylococcus aureus and Candida
      albicans. Blood plasma from bats collected during mid-hibernation at WNS-affected
      sites had higher bactericidal ability against E. coli and S. aureus, but lower
      fungicidal ability against C. albicans when compared with blood plasma from bats
      collected at unaffected sites. Within affected sites during mid-hibernation, we
      observed no difference in microbicidal ability between bats displaying obvious
      fungal infections compared to those without. Bactericidal ability against E. coli
      decreased significantly as hibernation progressed in bats collected from an
      affected site. Bactericidal ability against E. coli and fungicidal ability
      against C. albicans were positively correlated with body mass index (BMI) during
      late hibernation. We also compared complement activity against the three microbes
      within individuals and found that the ability of blood plasma from hibernating M.
      lucifugus to lyse microbial cells differed as follows: E. coli>S. aureus>C.
      albicans. Overall, bats affected by WNS experience both relatively elevated and
      reduced innate immune responses depending on the microbe tested, although the
      cause of observed immunological changes remains unknown. Additionally,
      considerable trade-offs may exist between energy conservation and immunological
      responses. Relationships between immune activity and torpor, including associated
      energy expenditure, are likely critical components in the development of WNS.

PMID- 22140442
TI  - Increased intrathecal high-avidity anti-tau antibodies in patients with multiple
      sclerosis.
AB  - BACKGROUND: Antibodies against tau protein indicate an interaction between the
      immune system and the neurocytoskeleton and therefore may reflect axonal injury
      in multiple sclerosis (MS). METHODOLOGY/PRINCIPAL FINDINGS: The levels and
      avidities of anti-tau IgG antibodies were measured using ELISA in paired
      cerebrospinal fluid (CSF) and serum samples obtained from 49 MS patients and 47
      controls. Anti-tau antibodies were significantly elevated intrathecally
      (p<0.0001) in the MS group. The CSF anti-tau antibody levels were lower in MS
      patients receiving therapy than those without treatment (p<0.05). The avidities
      of anti-tau antibodies were higher in the CSF than in the serum (MS group
      p<0.0001; controls p<0.005). Anti-tau avidities in the CSF were elevated in MS
      patients in comparison with controls (p<0.05), but not in serum. CONCLUSIONS: MS
      patients have higher levels of intrathecal anti-tau antibodies. Anti-tau
      antibodies have different avidities in different compartments with the highest
      values in the CSF of MS patients.

PMID- 22140441
TI  - A systematic analysis of the 3'UTR of HNF4A mRNA reveals an interplay of
      regulatory elements including miRNA target sites.
AB  - Dysfunction of hepatocyte nuclear factor 4alpha (HNF4alpha) has been linked to
      maturity onset diabetes of the young (MODY1), diabetes type II and possibly to
      renal cell carcinoma (RCC). Whereas diabetes causing mutations are well known,
      there are no HNF4A mutations found in RCC. Since so far analyses have been
      constricted to the promoter and open reading frame of HNF4A, we performed a
      systematic analysis of the human HNF4A 3'UTR. We identified a short (1724 nt) and
      long (3180 nt) 3'UTR that are much longer than the open reading frame and
      conferred a repressive effect in luciferase reporter assays in HEK293 and INS-1
      cells. By dissecting the 3'UTR into several pieces, we located two distinct
      elements of about 400 nt conferring a highly repressive effect. These negative
      elements A and B are counteracted by a balancer element of 39 nt located within
      the 5' end of the HNF4A 3'UTR. Dicer knock-down experiments implied that the
      HNF4A 3'UTR is regulated by miRNAs. More detailed analysis showed that miR-34a
      and miR-21 both overexpressed in RCC cooperate in downregulation of the HNF4A
      mRNA. One of the identified miR-34a binding sites is destroyed by SNP rs11574744.
      The identification of several regulatory elements within the HNF4A 3'UTR
      justifies the analysis of the 3'UTR sequence to explore the dysfunction of
      HNF4alpha in diabetes and RCC.

PMID- 22140443
TI  - Understanding the mechanism of insulin and insulin-like growth factor (IGF)
      receptor activation by IGF-II.
AB  - BACKGROUND: Insulin-like growth factor-II (IGF-II) promotes cell proliferation
      and survival and plays an important role in normal fetal development and
      placental function. IGF-II binds both the insulin-like growth factor receptor
      (IGF-1R) and insulin receptor isoform A (IR-A) with high affinity. Interestingly
      both IGF-II and the IR-A are often upregulated in cancer and IGF-II acts via both
      receptors to promote cancer proliferation. There is relatively little known about
      the mechanism of ligand induced activation of the insulin (IR) and IGF-1R. The
      recently solved IR structure reveals a folded over dimer with two potential
      ligand binding pockets arising from residues on each receptor half. Site-directed
      mutagenesis has mapped receptor residues important for ligand binding to two
      separate sites within the ligand binding pocket and we have recently shown that
      the IGFs have two separate binding surfaces which interact with the receptor
      sites 1 and 2. METHODOLOGY/PRINCIPAL FINDINGS: In this study we describe a series
      of partial IGF-1R and IR agonists generated by mutating Glu12 of IGF-II. By
      comparing receptor binding affinities, abilities to induce negative cooperativity
      and potencies in receptor activation, we provide evidence that residue Glu12
      bridges the two receptor halves leading to receptor activation.
      CONCLUSIONS/SIGNIFICANCE: This study provides novel insight into the mechanism of
      receptor binding and activation by IGF-II, which may be important for the future
      development of inhibitors of its action for the treatment of cancer.

PMID- 22140444
TI  - Myogenic reprogramming of bone marrow derived cells in a W41Dmd(mdx) deficient
      mouse model.
AB  - Lack of expression of dystrophin leads to degeneration of muscle fibers and
      infiltration of connective and adipose tissue. Cell transplantation therapy has
      been proposed as a treatment for intractable muscle degenerative disorders.
      Several reports have demonstrated the ability of bone-marrow derived cells (BMDC)
      to contribute to non-haematopoietic tissues including epithelium, heart, liver,
      skeletal muscle and brain following transplantation by means of fusion and
      reprogramming. A key issue is the extent to which fusion and reprogramming can
      occur in vivo, particularly under conditions of myogenic deterioration.To
      investigate the therapeutic potential of bone marrow transplantation in
      monogenetic myopathy, green fluorescent protein-positive (GFP+) bone marrow cells
      were transplanted into non-irradiated c-kit receptor-deficient (W41) mdx mice.
      This model allows BMDC reconstitution in the absence of irradiation induced
      myeloablation. We provide the first report of BMDC fusion in a W41Dmd(mdx)
      deficient mouse model.In the absence of irradiation induced injury, few GFP+
      cardiomyocytes and muscle fibres were detected 24 weeks post BMT. It was expected
      that the frequency of fusion in the hearts of W41Dmd(mdx) mice would be similar
      to frequencies observed in infarcted mice. Although, it is clear from this study
      that individual cardiomyocytes with monogenetic deficiencies can be rescued by
      fusion, it is as clear that in the absence of irradiation, the formation of
      stable and reprogrammed fusion hybrids occurs, with the current techniques, at
      very low levels in non-irradiated recipients.

PMID- 22140445
TI  - Xanthine oxidase-derived ROS upregulate Egr-1 via ERK1/2 in PA smooth muscle
      cells; model to test impact of extracellular ROS in chronic hypoxia.
AB  - Exposure of newborn calves to chronic hypoxia causes pulmonary artery (PA)
      hypertension and remodeling. Previous studies showed that the redox-sensitive
      transcription factor, early growth response-1 (Egr-1), is upregulated in the PA
      of chronically hypoxic calves and regulates cell proliferation. Furthermore, we
      established in mice a correlation between hypoxic induction of Egr-1 and reduced
      activity of extracellular superoxide dismutase (EC-SOD), an antioxidant that
      scavenges extracellular superoxide. We now hypothesize that loss of EC-SOD in
      chronically hypoxic calves leads to extracellular superoxide-mediated
      upregulation of Egr-1. To validate our hypothesis and identify the signaling
      pathways involved, we utilized PA tissue from normoxic and chronically hypoxic
      calves and cultured calf and human PA smooth muscle cells (PASMC). Total SOD
      activity was low in the PA tissue, and only the extracellular SOD component
      decreased with hypoxia. PA tissue of hypoxic calves showed increased oxidative
      stress and increased Egr-1 mRNA. To mimic the in vivo hypoxia-induced
      extracellular oxidant imbalance, cultured calf PASMC were treated with xanthine
      oxidase (XO), which generates extracellular superoxide and hydrogen peroxide. We
      found that 1) XO increased Egr-1 mRNA and protein, 2) XO induced the
      phosphorylation of ERK1/2 and, 3) pretreatment with an ERK1/2 inhibitor prevented
      induction of Egr-1 by XO. siRNA knock-down of EC-SOD in human PASMC also
      upregulated Egr-1 mRNA and protein, activated ERK1/2, and enhanced SMC
      proliferation and reduced apoptosis. We conclude that an oxidant/antioxidant
      imbalance arising from loss of EC-SOD in the PA with chronic hypoxia induces Egr
      1 via activation of ERK1/2 and contributes to pulmonary vascular remodeling.

PMID- 22140446
TI  - Technology-based self-care methods of improving antiretroviral adherence: a
      systematic review.
AB  - BACKGROUND: As HIV infection has shifted to a chronic condition, self-care
      practices have emerged as an important topic for HIV-positive individuals in
      maintaining an optimal level of health. Self-care refers to activities that
      patients undertake to maintain and improve health, such as strategies to achieve
      and maintain high levels of antiretroviral adherence. METHODOLOGY/PRINCIPAL
      FINDINGS: Technology-based methods are increasingly used to enhance
      antiretroviral adherence; therefore, we systematically reviewed the literature to
      examine technology-based self-care methods that HIV-positive individuals utilize
      to improve adherence. Seven electronic databases were searched from 1/1/1980
      through 12/31/2010. We included quantitative and qualitative studies. Among
      quantitative studies, the primary outcomes included ARV adherence, viral load,
      and CD4+ cell count and secondary outcomes consisted of quality of life, adverse
      effects, and feasibility/acceptability data. For qualitative/descriptive studies,
      interview themes, reports of use, and perceptions of use were summarized. Thirty
      six publications were included (24 quantitative and 12 qualitative/descriptive).
      Studies with exclusive utilization of medication reminder devices demonstrated
      less evidence of enhancing adherence in comparison to multi-component methods.
      CONCLUSIONS/SIGNIFICANCE: This systematic review offers support for self-care
      technology-based approaches that may result in improved antiretroviral adherence.
      There was a clear pattern of results that favored individually-tailored, multi
      function technologies, which allowed for periodic communication with health care
      providers rather than sole reliance on electronic reminder devices.

PMID- 22140447
TI  - Modulation of the host interferon response and ISGylation pathway by B. pertussis
      filamentous hemagglutinin.
AB  - Bordetella pertussis filamentous hemagglutinin (FHA) is a surface-associated and
      secreted protein that serves as a crucial adherence factor, and displays
      immunomodulatory activity in human peripheral blood mononuclear cells (PBMCs). In
      order to appreciate more fully the role of secreted FHA in pathogenesis, we
      analyzed FHA-induced changes in genome-wide transcript abundance in human PBMCs.
      Among the 683 known unique genes with greater than 3-fold change in transcript
      abundance following FHA treatment, 125 (18.3%) were identified as interferon
      (IFN)-regulated. Among the latter group were genes encoding several members of
      the IFN type I response, as well as 3 key components of the ISGylation pathway.
      Using real-time RT-PCR, we confirmed FHA-associated increases in transcript
      abundance for the genes encoding ubiquitin-like protein, ISG15, and its specific
      protease USP18. Western-blot analysis demonstrated the presence of both, free
      ISG15 and several ISGylated conjugates in FHA-stimulated PBMC lysates, but not in
      unstimulated cells. Intracellular FACS analysis provided evidence that monocytes
      and a natural killer-enriched cell population were the primary producers of ISG15
      in PBMCs after FHA stimulation. Our data reveal previously-unrecognized effects
      of B. pertussis FHA on host IFN and ISGylation responses, and suggest previously
      unsuspected mechanisms by which FHA may alter the outcome of the host-pathogen
      interaction.

PMID- 22140448
TI  - A conformational switch in the active site of BT_2972, a methyltransferase from
      an antibiotic resistant pathogen B. thetaiotaomicron.
AB  - Methylation is one of the most common biochemical reactions involved in cellular
      and metabolic functions and is catalysed by the action of methyltransferases.
      Bacteroides thetaiotaomicron is an antibiotic-resistant bacterium that confers
      resistance through methylation, and as yet, there is no report on the structure
      of methyltransferases from this bacterium. Here, we report the crystal structure
      of an AdoMet-dependent methyltransferase, BT_2972 and its complex with AdoMet and
      AdoHcy for B. thetaiotaomicron VPI-5482 strain along with isothermal titration
      calorimetric assessment of the binding affinities. Comparison of the apo and
      complexed BT_2972 structures reveals a significant conformational change between
      open and closed forms of the active site that presumably regulates the
      association with cofactors and may aid interaction with substrate. Together, our
      analysis suggests that BT_2972 is a small molecule methyltransferase and might
      catalyze two O-methylation reaction steps involved in the ubiquinone biosynthesis
      pathway.

PMID- 22140449
TI  - Voluntary medical male circumcision: a cross-sectional study comparing
      circumcision self-report and physical examination findings in Lesotho.
AB  - BACKGROUND: Overwhelming evidence, including three clinical trials, shows that
      male circumcision (MC) reduces the risk of HIV infection among men. However, data
      from recent Lesotho Demographic and Health Surveys do not demonstrate MC to be
      protective against HIV. These contradictory findings could partially be due to
      inaccurate self-reported MC status used to estimate MC prevalence. This study
      describes MC characteristics among men applying for Lesotho Defence Force
      recruitment and seeks to assess MC self-reported accuracy through comparison with
      physical-examination-based data. METHODS AND FINDINGS: During Lesotho Defence
      Force applicant screening in 2009, 241 (77%) of 312 men, aged 18-25 y, consented
      to a self-administered demographic and MC characteristic survey and physician
      performed genital examination. The extent of foreskin removal was graded on a
      scale of 1 (no evidence of MC) to 4 (complete MC). MC was self-reported by 27% (n
      = 64/239) of participants. Of the 64 men self-reporting being circumcised,
      physical exam showed that 23% had no evidence of circumcision, 27% had partial
      circumcision, and 50% had complete circumcision. Of the MCs reportedly performed
      by a medical provider, 3% were Grade 1 and 73% were Grade 4. Of the MCs
      reportedly performed by traditional circumcisers, 41% were Grade 1, while 28%
      were Grade 4. Among participants self-reporting being circumcised, the odds of MC
      status misclassification were seven times higher among those reportedly
      circumcised by initiation school personnel (odds ratio = 7.22; 95% CI = 2.29
      22.75). CONCLUSIONS: Approximately 27% of participants self-reported being
      circumcised. However, only 50% of these men had complete MC as determined by a
      physical exam. Given this low MC self-report accuracy, countries scaling up
      voluntary medical MC (VMMC) should obtain physical-exam-based MC data to guide
      service delivery and cost estimates. HIV prevention messages promoting VMMC
      should provide comprehensive education regarding the definition of VMMC.

PMID- 22140450
TI  - Voluntary medical male circumcision: a qualitative study exploring the challenges
      of costing demand creation in eastern and southern Africa.
AB  - BACKGROUND: This paper proposes an approach to estimating the costs of demand
      creation for voluntary medical male circumcision (VMMC) scale-up in 13 countries
      of eastern and southern Africa. It addresses two key questions: (1) what are the
      elements of a standardized package for demand creation? And (2) what challenges
      exist and must be taken into account in estimating the costs of demand creation?
      METHODS AND FINDINGS: We conducted a key informant study on VMMC demand creation
      using purposive sampling to recruit seven people who provide technical assistance
      to government programs and manage budgets for VMMC demand creation. Key
      informants provided their views on the important elements of VMMC demand creation
      and the most effective funding allocations across different types of
      communication approaches (e.g., mass media, small media, outreach/mobilization).
      The key finding was the wide range of views, suggesting that a standard package
      of core demand creation elements would not be universally applicable. This
      underscored the importance of tailoring demand creation strategies and estimates
      to specific country contexts before estimating costs. The key informant
      interviews, supplemented by the researchers' field experience, identified these
      issues to be addressed in future costing exercises: variations in the cost of
      VMMC demand creation activities by country and program, decisions about the
      quality and comprehensiveness of programming, and lack of data on critical
      elements needed to "trigger the decision" among eligible men. CONCLUSIONS: Based
      on this study's findings, we propose a seven-step methodological approach to
      estimate the cost of VMMC scale-up in a priority country, based on our key
      assumptions. However, further work is needed to better understand core components
      of a demand creation package and how to cost them. Notwithstanding the
      methodological challenges, estimating the cost of demand creation remains an
      essential element in deriving estimates of the total costs for VMMC scale-up in
      eastern and southern Africa.

PMID- 22140451
TI  - Cholesterol tuning of BK ethanol response is enantioselective, and is a function
      of accompanying lipids.
AB  - In the search to uncover ethanol's molecular mechanisms, the calcium and voltage
      activated, large conductance potassium channel (BK) has emerged as an important
      molecule. We examine how cholesterol content in bilayers of 1,2-dioleoyl-3
      phosphatidylethanolamine (DOPE)/sphingomyelin (SPM) and 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphatidylethanolamine (POPE)/1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphatidylserine (POPS) affect the function and ethanol sensitivity of BK. In
      addition, we examine how manipulation of cholesterol in biological membranes
      modulates ethanol's actions on BK. We report that cholesterol levels regulate the
      change in BK channel open probability elicited by 50 mM ethanol. Low levels of
      cholesterol (<20%, molar ratio) supports ethanol activation, while high levels of
      cholesterol leads to ethanol inhibition of BK. To determine if cholesterol
      affects BK and its sensitivity to ethanol through a direct cholesterol-protein
      interaction or via an indirect action on the lipid bilayer, we used the synthetic
      enantiomer of cholesterol (ent-CHS). We found that 20% and 40% ent-CHS had little
      effect on the ethanol sensitivity of BK, when compared with the same
      concentration of nat-CHS. We accessed the effects of ent-CHS and nat-CHS on the
      molecular organization of DOPE/SPM monolayers at the air/water interface. The
      isotherm data showed that ent-CHS condensed DOPE/SPM monolayer equivalently to
      nat-CHS at a 20% concentration, but slightly less at a 40% concentration. Atomic
      force microscopy (AFM) images of DOPE/SPM membranes in the presence of ent-CHS or
      nat-CHS prepared with LB technique or vesicle deposition showed no significant
      difference in topographies, supporting the interpretation that the differences in
      actions of nat-CHS and ent-CHS on BK channel are not likely from a generalized
      action on bilayers. We conclude that membrane cholesterol influences ethanol's
      modulation of BK in a complex manner, including an interaction with the channel
      protein. Finally, our results suggest that an understanding of membrane protein
      function and modulation is impossible unless protein and surrounding lipid are
      considered as a functional unit.

PMID- 22140452
TI  - Constructing a population-based research database from routine maternal screening
      records: a resource for studying alloimmunization in pregnant women.
AB  - BACKGROUND: Although screening for maternal red blood cell antibodies during
      pregnancy is a standard procedure, the prevalence and clinical consequences of
      non-anti-D immunization are poorly understood. The objective was to create a
      national database of maternal antibody screening results that can be linked with
      population health registers to create a research resource for investigating these
      issues. STUDY DESIGN AND METHODS: Each birth in the Swedish Medical Birth
      Register was uniquely identified and linked to the text stored in routine
      maternal antibody screening records in the time window from 9 months prior to 2
      weeks after the delivery date. These text records were subjected to a
      computerized search for specific antibodies using regular expressions. To
      illustrate the research potential of the resulting database, selected antibody
      prevalence rates are presented as tables and figures, and the complete data (from
      more than 60 specific antibodies) presented as online moving graphical displays.
      RESULTS: More than one million (1,191,761) births with valid screening
      information from 1982-2002 constitute the study population. Computerized coverage
      of screening increased steadily over time and varied by region as electronic
      records were adopted. To ensure data quality, we restricted analysis to birth
      records in areas and years with a sustained coverage of at least 80%,
      representing 920,903 births from 572,626 mothers in 17 of the 24 counties in
      Sweden. During the study period, non-anti-D and anti-D antibodies occurred in
      76.8/10,000 and 14.1/10,000 pregnancies respectively, with marked differences
      between specific antibodies over time. CONCLUSION: This work demonstrates the
      feasibility of creating a nationally representative research database from the
      routine maternal antibody screening records from an extended calendar period. By
      linkage with population registers of maternal and child health, such data are a
      valuable resource for addressing important clinical questions, such as the
      etiological significance of non-anti-D antibodies.

PMID- 22140454
TI  - BinTree seeking: a novel approach to mine both bi-sparse and cohesive modules in
      protein interaction networks.
AB  - Modern science of networks has brought significant advances to our understanding
      of complex systems biology. As a representative model of systems biology, Protein
      Interaction Networks (PINs) are characterized by a remarkable modular structures,
      reflecting functional associations between their components. Many methods were
      proposed to capture cohesive modules so that there is a higher density of edges
      within modules than those across them. Recent studies reveal that cohesively
      interacting modules of proteins is not a universal organizing principle in PINs,
      which has opened up new avenues for revisiting functional modules in PINs. In
      this paper, functional clusters in PINs are found to be able to form unorthodox
      structures defined as bi-sparse module. In contrast to the traditional cohesive
      module, the nodes in the bi-sparse module are sparsely connected internally and
      densely connected with other bi-sparse or cohesive modules. We present a novel
      protocol called the BinTree Seeking (BTS) for mining both bi-sparse and cohesive
      modules in PINs based on Edge Density of Module (EDM) and matrix theory. BTS
      detects modules by depicting links and nodes rather than nodes alone and its
      derivation procedure is totally performed on adjacency matrix of networks. The
      number of modules in a PIN can be automatically determined in the proposed BTS
      approach. BTS is tested on three real PINs and the results demonstrate that
      functional modules in PINs are not dominantly cohesive but can be sparse. BTS
      software and the supporting information are available at:
      www.csbio.sjtu.edu.cn/bioinf/BTS/.

PMID- 22140453
TI  - Personality is reflected in the brain's intrinsic functional architecture.
AB  - Personality describes persistent human behavioral responses to broad classes of
      environmental stimuli. Investigating how personality traits are reflected in the
      brain's functional architecture is challenging, in part due to the difficulty of
      designing appropriate task probes. Resting-state functional connectivity (RSFC)
      can detect intrinsic activation patterns without relying on any specific task.
      Here we use RSFC to investigate the neural correlates of the five-factor
      personality domains. Based on seed regions placed within two cognitive and
      affective 'hubs' in the brain--the anterior cingulate and precuneus--each domain
      of personality predicted RSFC with a unique pattern of brain regions. These
      patterns corresponded with functional subdivisions responsible for cognitive and
      affective processing such as motivation, empathy and future-oriented thinking.
      Neuroticism and Extraversion, the two most widely studied of the five constructs,
      predicted connectivity between seed regions and the dorsomedial prefrontal cortex
      and lateral paralimbic regions, respectively. These areas are associated with
      emotional regulation, self-evaluation and reward, consistent with the trait
      qualities. Personality traits were mostly associated with functional connections
      that were inconsistently present across participants. This suggests that although
      a fundamental, core functional architecture is preserved across individuals,
      variable connections outside of that core encompass the inter-individual
      differences in personality that motivate diverse responses.

PMID- 22140455
TI  - Neuronal chains for actions in the parietal lobe: a computational model.
AB  - The inferior part of the parietal lobe (IPL) is known to play a very important
      role in sensorimotor integration. Neurons in this region code goal-related motor
      acts performed with the mouth, with the hand and with the arm. It has been
      demonstrated that most IPL motor neurons coding a specific motor act (e.g.,
      grasping) show markedly different activation patterns according to the final goal
      of the action sequence in which the act is embedded (grasping for eating or
      grasping for placing). Some of these neurons (parietal mirror neurons) show a
      similar selectivity also during the observation of the same action sequences when
      executed by others. Thus, it appears that the neuronal response occurring during
      the execution and the observation of a specific grasping act codes not only the
      executed motor act, but also the agent's final goal (intention).In this work we
      present a biologically inspired neural network architecture that models
      mechanisms of motor sequences execution and recognition. In this network, pools
      composed of motor and mirror neurons that encode motor acts of a sequence are
      arranged in form of action goal-specific neuronal chains. The execution and the
      recognition of actions is achieved through the propagation of activity bursts
      along specific chains modulated by visual and somatosensory inputs.The
      implemented spiking neuron network is able to reproduce the results found in
      neurophysiological recordings of parietal neurons during task performance and
      provides a biologically plausible implementation of the action selection and
      recognition process.Finally, the present paper proposes a mechanism for the
      formation of new neural chains by linking together in a sequential manner neurons
      that represent subsequent motor acts, thus producing goal-directed sequences.

PMID- 22140456
TI  - Toll receptors type-2 and CR3 expression of canine monocytes and its correlation
      with immunohistochemistry and xenodiagnosis in visceral leishmaniasis.
AB  - The aim of the present study was to investigate TLR2 expression in peripheral
      blood monocytes from dogs naturally infected with Leishmania (Leishmania)
      infantum to determine whether it correlates with CD11b/CD18 (CR3) expression, and
      to evaluate the potential of dogs as sources of infection using phlebotomine
      xenodiagnosis. Forty eight dogs were serologically diagnosed with L. infantum
      infection by indirect immunofluorescence antibody test (IFAT) and enzyme linked
      immunosorbent assay (ELISA). Parasitological exams from bone-marrow aspirates
      were positive by PCR analysis. All dogs were clinical defined as symptomatic. Ear
      skin tissue samples were obtained for immunohistochemistry (IHQ) analysis. The
      potential of these dogs as a source of infection using phlebotomine xenodiagnosis
      (XENO) was evaluated. Flow cytometry was carried out on peripheral blood
      mononuclear cells using superficial receptors including CD14, CD11b, TLR2 and
      MHCII. IHQ ear skin tissue parasite load and XENO where done where we found a
      strict correlation (r = 0.5373). Dogs with higher expression of MFI of CD11b
      inside CD14 monocytes were represented by dogs without parasite ear tissue load
      that were unable to infect phlebotomines (IHQ-/XENO-). Dogs with lower expression
      of MFI of CD11b inside CD14 monocytes were represented by dogs with parasite ear
      tissue load and able to infect phlebotomines (IHQ+/XENO+) (p = 0,0032).
      Comparable results were obtained for MFI of MHCII (p = 0.0054). In addition,
      considering the population frequency of CD11b+TLR2+ and CD11b+MHCII+, higher
      values were obtained from dogs with IHQ-/XENO- than dogs with IHQ+/XENO+ (p =
      0.01; p = 0.0048, respectively). These data, together with the TLR2 and NO assays
      results (CD11b+TLR2+ and NO with higher values for dogs with IHQ-/XENO- than dogs
      with IHQ+/XENO+, led to the conclusion that IHQ-/XENO- dogs are more resistant or
      could modulate the cellular immune response essential for Leishmania tissue
      clearance.

PMID- 22140457
TI  - A quantitative method for the specific assessment of caspase-6 activity in cell
      culture.
AB  - Aberrant activation of caspase-6 has recently emerged as a major contributor to
      the pathogeneses of neurodegenerative disorders such as Alzheimer's and
      Huntington disease. Commercially available assays to measure caspase-6 activity
      commonly use the VEID peptide as a substrate. However these methods are not well
      suited to specifically assess caspase-6 activity in the presence of other,
      confounding protease activities, as often encountered in cell and tissue samples.
      Here we report the development of a method that overcomes this limitation by
      using a protein substrate, lamin A, which is highly specific for caspase-6
      cleavage at amino acid 230. Using a neo-epitope antibody against cleaved lamin A,
      we developed an electrochemiluminescence-based ELISA assay that is suitable to
      specifically detect and quantify caspase-6 activity in highly apoptotic cell
      extracts. The method is more sensitive than VEID-based assays and can be adapted
      to a high-content imaging platform for high-throughput screening. This method
      should be useful to screen for and characterize caspase-6 inhibitor compounds and
      other interventions to decrease intracellular caspase-6 activity for applications
      in neurodegenerative disorders.

PMID- 22140458
TI  - Fitness conferred by BCR-ABL kinase domain mutations determines the risk of pre
      existing resistance in chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is the first human malignancy to be successfully
      treated with a small molecule inhibitor, imatinib, targeting a mutant oncoprotein
      (BCR-ABL). Despite its successes, acquired resistance to imatinib leads to
      reduced drug efficacy and frequent progression of disease. Understanding the
      characteristics of pre-existing resistant cells is important for evaluating the
      benefits of first-line combination therapy with second generation inhibitors.
      However, due to limitations of assay sensitivity, determining the existence and
      characteristics of resistant cell clones at the start of therapy is difficult.
      Here we combined a mathematical modeling approach using branching processes with
      experimental data on the fitness changes (i.e., changes in net reproductive rate)
      conferred by BCR-ABL kinase domain mutations to investigate the likelihood,
      composition, and diversity of pre-existing resistance. Furthermore, we studied
      the impact of these factors on the response to tyrosine kinase inhibitors. Our
      approach predicts that in most patients, there is at most one resistant clone
      present at the time of diagnosis of their disease. Interestingly, patients are no
      more likely to harbor the most aggressive, pan-resistant T315I mutation than any
      other resistance mutation; however, T315I cells on average establish larger-sized
      clones at the time of diagnosis. We established that for patients diagnosed late,
      the relative benefit of combination therapy over monotherapy with imatinib is
      significant, while this benefit is modest for patients with a typically early
      diagnosis time. These findings, after pre-clinical validation, will have
      implications for the clinical management of CML: we recommend that patients with
      advanced-phase disease be treated with combination therapy with at least two
      tyrosine kinase inhibitors.

PMID- 22140459
TI  - Human hepatocyte growth factor promotes functional recovery in primates after
      spinal cord injury.
AB  - Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic
      factors have focused on reducing the area damaged by secondary, post-injury
      degeneration, to promote functional recovery. Hepatocyte growth factor (HGF),
      which is a potent mitogen for mature hepatocytes and a mediator of the
      inflammatory responses to tissue injury, was recently highlighted as a potent
      neurotrophic factor in the central nervous system. We previously reported that
      introducing exogenous HGF into the injured rodent spinal cord using a herpes
      simplex virus-1 vector significantly reduces the area of damaged tissue and
      promotes functional recovery. However, that study did not examine the therapeutic
      effects of administering HGF after injury, which is the most critical issue for
      clinical application. To translate this strategy to human treatment, we induced a
      contusive cervical SCI in the common marmoset, a primate, and then administered
      recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an
      original open field scoring system focusing on manual function, including reach
      and-grasp performance and hand placement in walking. The intrathecal rhHGF
      preserved the corticospinal fibers and myelinated areas, thereby promoting
      functional recovery. In vivo magnetic resonance imaging showed significant
      preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give
      rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers
      compared to the control group, indicating that this treatment did not induce or
      exacerbate allodynia. This is the first study to report the efficacy of rhHGF for
      treating SCI in non-human primates. In addition, this is the first presentation
      of a novel scale for assessing neurological motor performance in non-human
      primates after contusive cervical SCI.

PMID- 22140460
TI  - Comparative microarray analysis of intestinal lymphocytes following Eimeria
      acervulina, E. maxima, or E. tenella infection in the chicken.
AB  - Relative expression levels of immune- and non-immune-related mRNAs in chicken
      intestinal intraepithelial lymphocytes experimentally infected with Eimeria
      acervulina, E. maxima, or E. tenella were measured using a 10K cDNA microarray.
      Based on a cutoff of >2.0-fold differential expression compared with uninfected
      controls, relatively equal numbers of transcripts were altered by the three
      Eimeria infections at 1, 2, and 3 days post-primary infection. By contrast, E.
      tenella elicited the greatest number of altered transcripts at 4, 5, and 6 days
      post-primary infection, and at all time points following secondary infection.
      When analyzed on the basis of up- or down-regulated transcript levels over the
      entire 6 day infection periods, approximately equal numbers of up-regulated
      transcripts were detected following E. tenella primary (1,469) and secondary
      (1,459) infections, with a greater number of down-regulated mRNAs following
      secondary (1,063) vs. primary (890) infection. On the contrary, relatively few
      mRNA were modulated following primary infection with E. acervulina (35 up, 160
      down) or E. maxima (65 up, 148 down) compared with secondary infection (E.
      acervulina, 1,142 up, 1,289 down; E. maxima, 368 up, 1,349 down). With all three
      coccidia, biological pathway analysis identified the altered transcripts as
      belonging to the categories of "Disease and Disorder" and "Physiological System
      Development and Function". Sixteen intracellular signaling pathways were
      identified from the differentially expressed transcripts following Eimeria
      infection, with the greatest significance observed following E. acervulina
      infection. Taken together, this new information will expand our understanding of
      host-pathogen interactions in avian coccidiosis and contribute to the development
      of novel disease control strategies.

PMID- 22140462
TI  - Identification of Anaplasma marginale type IV secretion system effector proteins.
AB  - BACKGROUND: Anaplasma marginale, an obligate intracellular alphaproteobacterium
      in the order Rickettsiales, is a tick-borne pathogen and the leading cause of
      anaplasmosis in cattle worldwide. Complete genome sequencing of A. marginale
      revealed that it has a type IV secretion system (T4SS). The T4SS is one of seven
      known types of secretion systems utilized by bacteria, with the type III and IV
      secretion systems particularly prevalent among pathogenic Gram-negative bacteria.
      The T4SS is predicted to play an important role in the invasion and pathogenesis
      of A. marginale by translocating effector proteins across its membrane into
      eukaryotic target cells. However, T4SS effector proteins have not been identified
      and tested in the laboratory until now. RESULTS: By combining computational
      methods with phylogenetic analysis and sequence identity searches, we identified
      a subset of potential T4SS effectors in A. marginale strain St. Maries and chose
      six for laboratory testing. Four (AM185, AM470, AM705 [AnkA], and AM1141) of
      these six proteins were translocated in a T4SS-dependent manner using Legionella
      pneumophila as a reporter system. CONCLUSIONS: The algorithm employed to find
      T4SS effector proteins in A. marginale identified four such proteins that were
      verified by laboratory testing. L. pneumophila was shown to work as a model
      system for A. marginale and thus can be used as a screening tool for A. marginale
      effector proteins. The first T4SS effector proteins for A. marginale have been
      identified in this work.

PMID- 22140461
TI  - Human cardiac stem cells isolated from atrial appendages stably express c-kit.
AB  - The in vivo studies of myocardial infarct using c-ki+/Lin- cardiac stem cells
      (CSCs) are still in the early stage with margin or no beneficial effects for
      cardiac function. One of the potential reasons may be related to the absence of
      fully understanding the properties of these cells both in vitro and in vivo. In
      the present study, we aimed to systematically examine how CSCs adapted to in
      vitro cell processes and whether there is any cell contamination after long-term
      culture. Human CSCs were enzymatically isolated from the atrial appendages of
      patients. The fixed tissue sections, freshly isolated or cultured CSCs were then
      used for identification of c-kit+/Lin- cells, detection of cell contamination, or
      differentiation of cardiac lineages. By specific antibody staining, we
      demonstrated that tissue sections from atrial appendages contained less than
      0.036% c-kit+/Lin- cells. For the first time, we noted that without magnetic
      activated cell sorting (MACS), the percentages of c-kit+/Lin- cells gradually
      increased up to ~40% during continuously culture between passage 2 to 8, but
      could not exceed >80% unless c-kit MACS was carried out. The resulting c-kit+/Lin
      cells were negative for CD34, CD45, CD133, and Lin markers, but positive for KDR
      and CD31 in few patients after c-kit MACS. Lin depletion seemed unnecessary for
      enrichment of c-kit+/Lin- cell population. Following induced differentiation, c
      kit+/Lin- CSCs demonstrated strong differentiation towards cardiomyocytes but
      less towards smooth and endothelial cells. We concluded that by using an
      enzymatic dissociation method, a large number, or higher percentage, of relative
      pure human CSCs with stable expression of c-kit+ could be obtained from atrial
      appendage specimens within ~4 weeks following c-kit MACS without Lin depletion.
      This simple but cost-effective approach can be used to obtain enough numbers of
      stably-expressed c-kit+/Lin- cells for clinical trials in repairing myocardial
      infarction.

PMID- 22140463
TI  - Acute pancreatitis accelerates initiation and progression to pancreatic cancer in
      mice expressing oncogenic Kras in the nestin cell lineage.
AB  - Targeting of oncogenic Kras to the pancreatic Nestin-expressing embryonic
      progenitor cells and subsequently to the adult acinar compartment and Nestin
      expressing cells is sufficient for the development of low grade pancreatic
      intraepithelial neoplasia (PanIN) between 2 and 4 months. The mice die around 6
      month-old of unrelated causes, and it is therefore not possible to assess whether
      the lesions will progress to carcinoma. We now report that two brief episodes of
      caerulein-induced acute pancreatitis in 2 month-old mice causes rapid PanIN
      progression and pancreatic ductal adenocarcinoma (PDAC) development by 4 months
      of age. These events occur with similar frequency as observed in animals where
      the oncogene is targeted during embryogenesis to all pancreatic cell types. Thus,
      these data show that oncogenic Kras-driven PanIN originating in a non-ductal
      compartment can rapidly progress to PDAC when subjected to a brief inflammatory
      insult.

PMID- 22140464
TI  - Epigenetic modulation of miR-122 facilitates human embryonic stem cell self
      renewal and hepatocellular carcinoma proliferation.
AB  - The self-renewal capacity ascribed to hESCs is paralleled in cancer cell
      proliferation, suggesting that a common network of genes may facilitate the
      promotion of these traits. However, the molecular mechanisms that are involved in
      regulating the silencing of these genes as stem cells differentiate into
      quiescent cellular lineages remain poorly understood. Here, we show that a
      differentiated cell specific miR-122 exemplifies this regulatory attribute by
      suppressing the translation of a gene, Pkm2, which is commonly enriched in hESCs
      and liver cancer cells (HCCs), and facilitates self-renewal and proliferation.
      Through a series of gene expression analysis, we show that miR-122 expression is
      highly elevated in quiescent human primary hepatocytes (hPHs) but lost or
      attenuated in hESCs and HCCs, while an opposing expression pattern is observed
      for Pkm2. Depleting hESCs and HCCs of Pkm2, or overexpressing miR-122, leads to a
      common deficiency in self-renewal and proliferation. Likewise, during the
      differentiation process of hESCs into hepatocytes, a reciprocal expression
      pattern is observed between miR-122 and Pkm2. An examination of the genomic
      region upstream of miR-122 uncovered hyper-methylation in hESCs and HCCs, while
      the same region is de-methylated and occupied by a transcription initiating
      protein, RNA polymerase II (RNAPII), in hPHs. These findings indicate that one
      possible mechanism by which hESC self-renewal is modulated in quiescent hepatic
      derivatives of hESCs is through the regulatory activity of a differentiated cell
      specific miR-122, and that a failure to properly turn "on" this miRNA is observed
      in uncontrollably proliferating HCCs.

PMID- 22140465
TI  - Early events in xenograft development from the human embryonic stem cell line
      HS181--resemblance with an initial multiple epiblast formation.
AB  - Xenografting is widely used for assessing in vivo pluripotency of human stem cell
      populations. Here, we report on early to late events in the development of mature
      experimental teratoma from a well-characterized human embryonic stem cell (HESC)
      line, HS181. The results show an embryonic process, increasingly chaotic. Active
      proliferation of the stem cell derived cellular progeny was detected already at
      day 5, and characterized by the appearance of multiple sites of engraftment, with
      structures of single or pseudostratified columnar epithelium surrounding small
      cavities. The striking histological resemblance to developing embryonic ectoderm,
      and the formation of epiblast-like structures was supported by the expression of
      the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural
      marker NESTIN was uniformly expressed, while markers linked to gastrulation, such
      as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5
      indicated differentiation comparable to the most early transient cell populations
      in human post implantation development. Confirming and expanding on previous
      findings from HS181 xenografts, these early events were followed by an
      increasingly chaotic development, incorporated in the formation of a benign
      teratoma with complex embryonic components. In the mature HS181 teratomas not all
      types of organs/tissues were detected, indicating a restricted differentiation,
      and a lack of adequate spatial developmental cues during the further teratoma
      formation. Uniquely, a kinetic alignment of rare complex structures was made to
      human embryos at diagnosed gestation stages, showing minor kinetic deviations
      between HS181 teratoma and the human counterpart.

PMID- 22140466
TI  - SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in
      the R6/2 mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is a progressive neurological disorder for which there
      are no disease-modifying treatments. Transcriptional dysregulation is a major
      molecular feature of HD, which significantly contributes to disease progression.
      Therefore, the development of histone deacetylase (HDAC) inhibitors as
      therapeutics for HD has been energetically pursued. Suberoylanilide hydroxamic
      acid (SAHA) - a class I HDAC as well an HDAC6 inhibitor, improved motor
      impairment in the R6/2 mouse model of HD. Recently it has been found that SAHA
      can also promote the degradation of HDAC4 and possibly other class IIa HDACs at
      the protein level in various cancer cell lines. To elucidate whether SAHA is a
      potent modifier of HDAC protein levels in vivo, we performed two independent
      mouse trials. Both WT and R6/2 mice were chronically treated with SAHA and
      vehicle. We found that prolonged SAHA treatment causes the degradation of HDAC4
      in cortex and brain stem, but not hippocampus, without affecting its transcript
      levels in vivo. Similarly, SAHA also decreased HDAC2 levels without modifying the
      expression of its mRNA. Consistent with our previous data, SAHA treatment
      diminishes Hdac7 transcript levels in both wild type and R6/2 brains and
      unexpectedly was found to decrease Hdac11 in R6/2 but not wild type. We
      investigated the effects of SAHA administration on well-characterised molecular
      readouts of disease progression. We found that SAHA reduces SDS-insoluble
      aggregate load in the cortex and brain stem but not in the hippocampus of the
      R6/2 brains, and that this was accompanied by restoration of Bdnf cortical
      transcript levels.

PMID- 22140467
TI  - Application of the malaria management model to the analysis of costs and benefits
      of DDT versus non-DDT malaria control.
AB  - INTRODUCTION: DDT is considered to be the most cost-effective insecticide for
      combating malaria. However, it is also the most environmentally persistent and
      can pose risks to human health when sprayed indoors. Therefore, the use of DDT
      for vector control remains controversial. METHODS: In this paper we develop a
      computer-based simulation model to assess some of the costs and benefits of the
      continued use of DDT for Indoor Residual Spraying (IRS) versus its rapid phase
      out. We apply the prototype model to the aggregated sub Saharan African region.
      For putting the question about the continued use of DDT for IRS versus its rapid
      phase out into perspective we calculate the same costs and benefits for
      alternative combinations of integrated vector management interventions. RESULTS:
      Our simulation results confirm that the current mix of integrated vector
      management interventions with DDT as the main insecticide is cheaper than the
      same mix with alternative insecticides when only direct costs are considered.
      However, combinations with a stronger focus on insecticide-treated bed nets and
      environmental management show higher levels of cost-effectiveness than
      interventions with a focus on IRS. Thus, this focus would also allow phasing out
      DDT in a cost-effective manner. Although a rapid phase out of DDT for IRS is the
      most expensive of the tested intervention combinations it can have important
      economic benefits in addition to health and environmental impacts that are
      difficult to assess in monetary terms. Those economic benefits captured by the
      model include the avoided risk of losses in agricultural exports. CONCLUSIONS:
      The prototype simulation model illustrates how a computer-based scenario analysis
      tool can inform debates on malaria control policies in general and on the
      continued use of DDT for IRS versus its rapid phase out in specific. Simulation
      models create systematic mechanisms for analyzing alternative interventions and
      making informed trade offs.

PMID- 22140468
TI  - Existence of inverted profile in chemically responsive molecular pathways in the
      zebrafish liver.
AB  - How a living organism maintains its healthy equilibrium in response to endless
      exposure of potentially harmful chemicals is an important question in current
      biology. By transcriptomic analysis of zebrafish livers treated by various
      chemicals, we defined hubs as molecular pathways that are frequently perturbed by
      chemicals and have high degree of functional connectivity to other pathways. Our
      network analysis revealed that these hubs were organized into two groups showing
      inverted functionality with each other. Intriguingly, the inverted activity
      profiles in these two groups of hubs were observed to associate only with
      toxicopathological states but not with physiological changes. Furthermore, these
      inverted profiles were also present in rat, mouse, and human under certain
      toxicopathological conditions. Thus, toxicopathological-associated anti
      correlated profiles in hubs not only indicate their potential use in diagnosis
      but also development of systems-based therapeutics to modulate gene expression by
      chemical approach in order to rewire the deregulated activities of hubs back to
      normal physiology.

PMID- 22140469
TI  - Induction of antibodies in rhesus macaques that recognize a fusion-intermediate
      conformation of HIV-1 gp41.
AB  - A component to the problem of inducing broad neutralizing HIV-1 gp41 membrane
      proximal external region (MPER) antibodies is the need to focus the antibody
      response to the transiently exposed MPER pre-hairpin intermediate neutralization
      epitope. Here we describe a HIV-1 envelope (Env) gp140 oligomer prime followed by
      MPER peptide-liposomes boost strategy for eliciting serum antibody responses in
      rhesus macaques that bind to a gp41 fusion intermediate protein. This Env
      liposome immunization strategy induced antibodies to the 2F5 neutralizing epitope
      664DKW residues, and these antibodies preferentially bound to a gp41 fusion
      intermediate construct as well as to MPER scaffolds stabilized in the 2F5-bound
      conformation. However, no serum lipid binding activity was observed nor was serum
      neutralizing activity for HIV-1 pseudoviruses present. Nonetheless, the Env
      liposome prime-boost immunization strategy induced antibodies that recognized a
      gp41 fusion intermediate protein and was successful in focusing the antibody
      response to the desired epitope.

PMID- 22140470
TI  - Stem cell antigen-1 (sca-1) regulates mammary tumor development and cell
      migration.
AB  - BACKGROUND: Stem cell antigen-1 (Sca-1 or Ly6A) is a glycosyl phostidylinositol
      (GPI)-anchored cell surface protein associated with both stem and progenitor
      activity, as well as tumor initiating-potential. However, at present the
      functional role for Sca-1 is poorly defined. METHODOLOGY/PRINCIPAL FINDINGS: To
      investigate the role of Sca-1 in mammary tumorigenesis, we used a mammary cell
      line derived from a MMTV-Wnt1 mouse mammary tumor that expresses high levels of
      endogenous Sca-1. Using shRNA knockdown, we demonstrate that Sca-1 expression
      controls cell proliferation during early tumor progression in mice. Functional
      limiting dilution transplantations into recipient mice demonstrate that
      repression of Sca-1 increases the population of tumor propagating cells. In
      scratch monolayer assays, Sca-1 enhances cell migration. In addition, knockdown
      of Sca-1 was shown to affect cell adhesion to a number of different extracellular
      matrix components. Microarray analysis indicates that repression of Sca-1 leads
      to changes in expression of genes involved in proliferation, cell migration,
      immune response and cell organization. CONCLUSIONS/SIGNIFICANCE: Sca-1 exerts
      marked effects on cellular activity and tumorgenicity both in vitro and in vivo.
      A better understanding of Sca-1 function may provide insight into the broader
      role of GPI-anchored cell surface proteins in cancer.

PMID- 22140472
TI  - Differential combination of cytokine and interferon- gamma +874 T/A polymorphisms
      determines disease severity in pulmonary tuberculosis.
AB  - BACKGROUND: Mycobacterium tuberculosis infects nearly 1/3 of the world population
      and this reservoir forms the largest pool from which new cases arise. Among the
      cytokines, IFN-gamma is a key determinant in protection against tuberculosis.
      Single nucleotide polymorphisms (SNPs) in IFN-gamma gene (+874 T/A) which
      determine TT high ((hi)), AA low ((lo)) and TA intermediate ((int)) responder
      phenotypes have shown variable associations with tuberculosis disease outcome in
      different ethnic populations. The objective of the current study was to analyze
      IFN-gamma gene combinations with other IFN-gamma regulating cytokine genes (IL
      10, TNF -alpha, IL-6) to see the effect of gene- combinations on disease severity
      outcome in pulmonary tuberculosis. METHODS AND FINDINGS: Study groups comprised
      of pulmonary TB patients stratified according to lung tissue involvement into
      mild (Pmd = 74) or advance (Pad = 23) lung disease and compared with healthy
      controls (TBNA = 166). Genotype analysis was carried out using amplification
      refractory mutation system-PCR (ARMS-PCR). IFN-gamma gene (+874 T/A) functional
      SNP combinations in TNFalpha (-308 G/A), IL-10 (-1082 A/G) and IL-6 (-174 G/C)
      were analyzed. Single gene analysis (Pearson chi2) showed a dominant association
      of IFN-gamma TT (hi) genotype (p = 0.001) and T allele (p = 0.001) with mild
      disease. IFN-gamma(lo) -IL-10(lo) genotype combination was associated with
      advanced disease (p = 0.002). IFN-gamma(hi) -IL-6(hi) combination was associated
      with mild disease (p = 0.0005) while IFN-gamma(lo) -IL-6(int) was associated with
      protection against both forms of pulmonary disease (p = 0.002). CONCLUSION: Our
      results show that a limited number of IFN-gamma gene combinations with other
      cytokine functional SNPs determine the outcome of disease severity in
      tuberculosis.

PMID- 22140471
TI  - Characterization of PTZ-induced seizure susceptibility in a down syndrome mouse
      model that overexpresses CSTB.
AB  - Down syndrome (DS) is a complex genetic syndrome characterized by intellectual
      disability, dysmorphism and variable additional physiological traits. Current
      research progress has begun to decipher the neural mechanisms underlying
      cognitive impairment, leading to new therapeutic perspectives. Pentylenetetrazol
      (PTZ) has recently been found to have positive effects on learning and memory
      capacities of a DS mouse model and is foreseen to treat DS patients. But PTZ is
      also known to be a convulsant drug at higher dose and DS persons are more prone
      to epileptic seizures than the general population. This raises concerns over what
      long-term effects of treatment might be in the DS population. The cause of
      increased propensity for epilepsy in the DS population and which Hsa21 gene(s)
      are implicated remain unknown. Among Hsa21 candidate genes in epilepsy, CSTB,
      coding for the cystein protease inhibitor cystatin B, is involved in progressive
      myoclonus epilepsy and ataxia in both mice and human. Thus we aim to evaluate the
      effect of an increase in Cstb gene dosage on spontaneous epileptic activity and
      susceptibility to PTZ-induced seizure. To this end we generated a new mouse model
      trisomic for Cstb by homologous recombination. We verified that increasing copy
      number of Cstb from Trisomy (Ts) to Tetrasomy (Tt) was driving overexpression of
      the gene in the brain, we checked transgenic animals for presence of locomotor
      activity and electroencephalogram (EEG) abnormalities characteristic of myoclonic
      epilepsy and we tested if those animals were prone to PTZ-induced seizure.
      Overall, the results of the analysis shows that an increase in Cstb does not
      induce any spontaneous epileptic activity and neither increase or decrease the
      propensity of Ts and Tt mice to myoclonic seizures suggesting that Ctsb dosage
      should not interfere with PTZ-treatment.

PMID- 22140474
TI  - Genome-wide mapping of copy number variation in humans: comparative analysis of
      high resolution array platforms.
AB  - Accurate and efficient genome-wide detection of copy number variants (CNVs) is
      essential for understanding human genomic variation, genome-wide CNV association
      type studies, cytogenetics research and diagnostics, and independent validation
      of CNVs identified from sequencing based technologies. Numerous, array-based
      platforms for CNV detection exist utilizing array Comparative Genome
      Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) genotyping or both. We
      have quantitatively assessed the abilities of twelve leading genome-wide CNV
      detection platforms to accurately detect Gold Standard sets of CNVs in the genome
      of HapMap CEU sample NA12878, and found significant differences in performance.
      The technologies analyzed were the NimbleGen 4.2 M, 2.1 M and 3*720 K Whole
      Genome and CNV focused arrays, the Agilent 1*1 M CGH and High Resolution and
      2*400 K CNV and SNP+CGH arrays, the Illumina Human Omni1Quad array and the
      Affymetrix SNP 6.0 array. The Gold Standards used were a 1000 Genomes Project
      sequencing-based set of 3997 validated CNVs and an ultra high-resolution aCGH
      based set of 756 validated CNVs. We found that sensitivity, total number, size
      range and breakpoint resolution of CNV calls were highest for CNV focused arrays.
      Our results are important for cost effective CNV detection and validation for
      both basic and clinical applications.

PMID- 22140473
TI  - Stat3 mediates expression of autotaxin in breast cancer.
AB  - We determined that signal transducer and activator of transcription 3 (Stat3) is
      tyrosine phosphorylated in 37% of primary breast tumors and 63% of paired
      metastatic axillary lymph nodes. Examination of the distribution of tyrosine
      phosphorylated (pStat3) in primary tumors revealed heterogenous expression within
      the tumor with the highest levels found in cells on the edge of tumors with
      relatively lower levels in the central portion of tumors. In order to determine
      Stat3 target genes that may be involved in migration and metastasis, we
      identified those genes that were differentially expressed in primary breast
      cancer samples as a function of pStat3 levels. In addition to known Stat3
      transcriptional targets (Twist, Snail, Tenascin-C and IL-8), we identified ENPP2
      as a novel Stat3 regulated gene, which encodes autotaxin (ATX), a secreted
      lysophospholipase which mediates mammary tumorigenesis and cancer cell migration.
      A positive correlation between nuclear pStat3 and ATX was determined by
      immunohistochemical analysis of primary breast cancer samples and matched
      axillary lymph nodes and in several breast cancer derived cell lines. Inhibition
      of pStat3 or reducing Stat3 expression led to a decrease in ATX levels and cell
      migration. An association between Stat3 and the ATX promoter, which contains a
      number of putative Stat3 binding sites, was determined by chromatin
      immunoprecipitation. These observations suggest that activated Stat3 may regulate
      the migration of breast cancer cells through the regulation of ATX.

PMID- 22140475
TI  - 'Multi-epitope-targeted' immune-specific therapy for a multiple sclerosis-like
      disease via engineered multi-epitope protein is superior to peptides.
AB  - Antigen-induced peripheral tolerance is potentially one of the most efficient and
      specific therapeutic approaches for autoimmune diseases. Although highly
      effective in animal models, antigen-based strategies have not yet been translated
      into practicable human therapy, and several clinical trials using a single
      antigen or peptidic-epitope in multiple sclerosis (MS) yielded disappointing
      results. In these clinical trials, however, the apparent complexity and dynamics
      of the pathogenic autoimmunity associated with MS, which result from the
      multiplicity of potential target antigens and "epitope spread", have not been
      sufficiently considered. Thus, targeting pathogenic T-cells reactive against a
      single antigen/epitope is unlikely to be sufficient; to be effective,
      immunospecific therapy to MS should logically neutralize concomitantly T-cells
      reactive against as many major target antigens/epitopes as possible. We
      investigated such "multi-epitope-targeting" approach in murine experimental
      autoimmune encephalomyelitis (EAE) associated with a single ("classical") or
      multiple ("complex") anti-myelin autoreactivities, using cocktail of different
      encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated
      Y-MSPc) encompassing rationally selected MS-relevant epitopes of five major
      myelin antigens, as "multi-epitope-targeting" agents. Y-MSPc was superior to
      peptide(s) in concomitantly downregulating pathogenic T-cells reactive against
      multiple myelin antigens/epitopes, via inducing more effective, longer lasting
      peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+
      regulatory T-cells). Y-MSPc was also consistently more effective than the disease
      inducing single peptide or peptide cocktail, not only in suppressing the
      development of "classical" or "complex EAE" or ameliorating ongoing disease, but
      most importantly, in reversing chronic EAE. Overall, our data emphasize that a
      "multi-epitope-targeting" strategy is required for effective immune-specific
      therapy of organ-specific autoimmune diseases associated with complex and dynamic
      pathogenic autoimmunity, such as MS; our data further demonstrate that the "multi
      epitope-targeting" approach to therapy is optimized through specifically designed
      multi-epitope-proteins, rather than myelin peptide cocktails, as "multi-epitope
      targeting" agents. Such artificial multi-epitope proteins can be tailored to
      other organ-specific autoimmune diseases.

PMID- 22140476
TI  - Phosphatidylserine exposure by Toxoplasma gondii is fundamental to balance the
      immune response granting survival of the parasite and of the host.
AB  - Phosphatidylserine (PS) exposure on the cell surface indicates apoptosis, but has
      also been related to evasion mechanisms of parasites, a concept known as
      apoptotic mimicry. Toxoplasma gondii mimics apoptotic cells by exposing PS,
      inducing secretion of TGF-beta1 by infected activated macrophages leading to
      degradation of inducible nitric oxide (NO) synthase, NO production inhibition and
      consequently persisting in these cells. Here PS+ and PS- subpopulation of
      tachyzoites were separated and the entrance mechanism, growth and NO inhibition
      in murine macrophages, and mice survival and pathology were analyzed. Infection
      index in resident macrophages was similar for both PS subpopulations but lower
      when compared to the total T. gondii population. Growth in resident macrophages
      was higher for the total T. gondii population, intermediate for the PS+ and lower
      for the PS- subpopulation. Production of NO by activated macrophages was
      inhibited after infection with the PS+ subpopulation and the total populations of
      tachyzoites. However, the PS- subpopulation was not able to inhibit NO
      production. PS+ subpopulation invaded macrophages by active penetration as
      indicated by tight-fitting vacuoles, but the PS- subpopulation entered
      macrophages by phagocytosis as suggested by loose-fitting vacuoles containing
      these tachyzoites. The entrance mechanism of both subpopulations was confirmed in
      a non-professional phagocytic cell line where only the PS+ tachyzoites were found
      inside these cells in tight-fitting vacuoles. Both subpopulations of T. gondii
      killed mice faster than the total population. Clear signs of inflammation and no
      tachyzoites were seen in the peritoneal cavity of mice infected with the PS-
      subpopulation. Moreover, mice infected with the PS+ subpopulation had no sign of
      inflammation and the parasite burden was intense. These results show that PS+ and
      PS- subpopulations of T. gondii are necessary for a successful toxoplasma
      infection indicating that both subpopulations are required to maintain the
      balance between inflammation and parasite growth.

PMID- 22140477
TI  - Identifying highly conserved and highly differentiated gene ontology categories
      in human populations.
AB  - Detecting and interpreting certain system-level characteristics associated with
      human population genetic differences is a challenge for human geneticists. In
      this study, we conducted a population genetic study using the HapMap genotype
      data to identify certain special Gene Ontology (GO) categories associated with
      high/low genetic difference among 11 Hapmap populations. Initially, the genetic
      differences in each gene region among these populations were measured using
      allele frequency, linkage disequilibrium (LD) pattern, and transferability of
      tagSNPs. The associations between each GO term and these genetic differences were
      then identified. The results showed that cellular process, catalytic activity,
      binding, and some of their sub-terms were associated with high levels of genetic
      difference, and genes involved in these functional categories displayed, on
      average, high genetic diversity among different populations. By contrast,
      multicellular organismal processes, molecular transducer activity, and some of
      their sub-terms were associated with low levels of genetic difference. In
      particular, the neurological system process under the multicellular organismal
      process category had low levels of genetic difference; the neurological function
      also showed high evolutionary conservation between species in some previous
      studies. These results may provide a new insight into the understanding of human
      evolutionary history at the system-level.

PMID- 22140478
TI  - Raloxifene and desmethylarzoxifene block estrogen-induced malignant
      transformation of human breast epithelial cells.
AB  - There is association between exposure to estrogens and the development and
      progression of hormone-dependent gynecological cancers. Chemical carcinogenesis
      by catechol estrogens derived from oxidative metabolism is thought to contribute
      to breast cancer, yet exact mechanisms remain elusive. Malignant transformation
      was studied in MCF-10A human mammary epithelial cells, since estrogens are not
      proliferative in this cell line. The human and equine estrogen components of
      estrogen replacement therapy (ERT) and their catechol metabolites were studied,
      along with the influence of co-administration of selective estrogen receptor
      modulators (SERMs), raloxifene and desmethyl-arzoxifene (DMA), and histone
      deacetylase inhibitors. Transformation was induced by human estrogens, and
      selectively by the 4-OH catechol metabolite, and to a lesser extent by an equine
      estrogen metabolite. The observed estrogen-induced upregulation of CYP450 1B1 in
      estrogen receptor negative MCF-10A cells, was compatible with a causal role for 4
      OH catechol estrogens, as was attenuated transformation by CYP450 inhibitors.
      Estrogen-induced malignant transformation was blocked by SERMs correlating with a
      reduction in formation of nucleobase catechol estrogen (NCE) adducts and
      formation of 8-oxo-dG. NCE adducts can be formed consequent to DNA abasic site
      formation, but NCE adducts were also observed on incubation of estrogen quinones
      with free nucleotides. These results suggest that NCE adducts may be a biomarker
      for cellular electrophilic stress, which together with 8-oxo-dG as a biomarker of
      oxidative stress correlate with malignant transformation induced by estrogen
      oxidative metabolites. The observed attenuation of transformation by SERMs
      correlated with these biomarkers and may also be of clinical significance in
      breast cancer chemoprevention.

PMID- 22140479
TI  - Potential tumor suppressor NESG1 as an unfavorable prognosis factor in
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Recently we identified nasopharyngeal epithelium specific protein 1
      (NESG1) as a potential tumor suppressor in nasopharyngeal carcinoma (NPC). The
      purpose of this study is to investigate the involvement of NESG1 in tumor
      progression and prognosis of human NPC. METHODOLOGY/PRINCIPAL FINDINGS: NESG1
      protein expression in NPC was examined. Survival analysis was performed using
      Kaplan-Meier method. The effect of NESG1 on cell proliferation, migration, and
      invasion were also investigated. RESULTS: NESG1 expression was downregulated in
      atypical hyperplasia and NPC samples compared to normal and squamous nasopharynx
      tissues. Reduced protein expression was negatively associated with the status of
      NPC progression. Patients with lower NESG1 expression had a shorter overall
      survival and disease-free time than did patients with higher NESG1 expression.
      Multivariate analysis suggested NESG1 expression as an independent prognostic
      indicator for NPC patient survival. Proliferation, migration, and invasion
      ability were significantly increased in cell lines following lentiviral-mediated
      shRNA suppression of NESG1 expression. Microarray analysis indicated that NESG1
      participated in multiple pathways, including MAPK signaling and cell cycle
      regulation. Finally, DNA methylation microarray examination revealed a lack of
      hypermethylation at the NESG1 promoter, suggesting other mechanisms are involved
      in suppressing NESG1 expression in NPC. CONCLUSION: Our studies are the first to
      demonstrate that decreased NESG1 expression is an unfavorable prognostic factor
      for NPC.

PMID- 22140480
TI  - SNPs and other features as they predispose to complex disease: genome-wide
      predictive analysis of a quantitative phenotype for hypertension.
AB  - Though recently they have fallen into some disrepute, genome-wide association
      studies (GWAS) have been formulated and applied to understanding essential
      hypertension. The principal goal here is to use data gathered in a GWAS to gauge
      the extent to which SNPs and their interactions with other features can be
      combined to predict mean arterial blood pressure (MAP) in 3138 pre-menopausal and
      naturally post-menopausal white women. More precisely, we quantify the extent to
      which data as described permit prediction of MAP beyond what is possible from
      traditional risk factors such as blood cholesterol levels and glucose levels. Of
      course, these traditional risk factors are genetic, though typically not
      explicitly so. In all, there were 44 such risk factors/clinical variables
      measured and 377,790 single nucleotide polymorphisms (SNPs) genotyped. Data for
      women we studied are from first visit measurements taken as part of the
      Atherosclerotic Risk in Communities (ARIC) study. We begin by assessing non-SNP
      features in their abilities to predict MAP, employing a novel regression
      technique with two stages, first the discovery of main effects and next discovery
      of their interactions. The long list of SNPs genotyped is reduced to a manageable
      list for combining with non-SNP features in prediction. We adapted Efron's local
      false discovery rate to produce this reduced list. Selected non-SNP and SNP
      features and their interactions are used to predict MAP using adaptive linear
      regression. We quantify quality of prediction by an estimated coefficient of
      determination (R(2)). We compare the accuracy of prediction with and without
      information from SNPs.

PMID- 22140482
TI  - Wheeze in preschool age is associated with pulmonary bacterial infection and
      resolves after antibiotic therapy.
AB  - BACKGROUND: Neonates with airways colonized by Haemophilus influenzae,
      Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for
      recurrent wheeze which may resemble asthma early in life. It is not clear whether
      chronic colonization by these pathogens is causative for severe persistent wheeze
      in some preschool children and whether these children might benefit from
      antibiotic treatment. We assessed the relevance of bacterial colonization and
      chronic airway infection in preschool children with severe persistent wheezing
      and evaluated the outcome of long-time antibiotic treatment on the clinical
      course in such children. METHODOLOGY/PRINCIPAL FINDINGS: Preschool children (n =
      42) with severe persistent wheeze but no symptoms of acute pulmonary infection
      were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential
      cell counts and microbiological and virological analyses were performed on BAL
      samples. Patients diagnosed with bacterial infection were treated with
      antibiotics for 2-16 weeks (n = 29). A modified ISAAC questionnaire was used for
      follow-up assessment of children at least 6 months after bronchoscopy. Of the 42
      children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20
      (59%) of this subgroup had elevated bacterial counts (>= 104 colony forming units
      per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus
      pneumoniae and Moraxella catarrhalis were the most frequently isolated species.
      After treatment with appropriate antibiotics 92% of patients showed a marked
      improvement of symptoms upon follow-up examination. CONCLUSIONS/SIGNIFICANCE:
      Chronic bacterial infections are relevant in a subgroup of preschool children
      with persistent wheezing and such children benefit significantly from antibiotic
      therapy.

PMID- 22140481
TI  - Phosphodiesterase-5 inhibition mimics intermittent reoxygenation and improves
      cardioprotection in the hypoxic myocardium.
AB  - Although chronic hypoxia is a claimed myocardial risk factor reducing tolerance
      to ischemia/reperfusion (I/R), intermittent reoxygenation has beneficial effects
      and enhances heart tolerance to I/R. AIM OF THE STUDY: To test the hypothesis
      that, by mimicking intermittent reoxygenation, selective inhibition of
      phosphodiesterase-5 activity improves ischemia tolerance during hypoxia. Adult
      male Sprague-Dawley rats were exposed to hypoxia for 15 days (10% O2) and treated
      with placebo, sildenafil (1.4 mg/kg/day, i. p.), intermittent reoxygenation (1
      h/day exposure to room air) or both. Controls were normoxic hearts. To assess
      tolerance to I/R all hearts were subjected to 30-min regional ischemia by left
      anterior descending coronary artery ligation followed by 3 h-reperfusion. Whereas
      hypoxia depressed tolerance to I/R, both sildenafil and intermittent
      reoxygenation reduced the infarct size without exhibiting cumulative effects. The
      changes in myocardial cGMP, apoptosis (DNA fragmentation), caspase-3 activity
      (alternative marker for cardiomyocyte apoptosis), eNOS phosphorylation and Akt
      activity paralleled the changes in cardioprotection. However, the level of plasma
      nitrates and nitrites was higher in the sildenafil+intermittent reoxygenation
      than sildenafil and intermittent reoxygenation groups, whereas total eNOS and Akt
      proteins were unchanged throughout. CONCLUSIONS: Sildenafil administration has
      the potential to mimic the cardioprotective effects led by intermittent
      reoxygenation, thereby opening the possibility to treat patients unable to be
      reoxygenated through a pharmacological modulation of NO-dependent mechanisms.

PMID- 22140483
TI  - A flavonoid, luteolin, cripples HIV-1 by abrogation of tat function.
AB  - Despite the effectiveness of combination antiretroviral treatment (cART) against
      HIV-1, evidence indicates that residual infection persists in different cell
      types. Intensification of cART does not decrease the residual viral load or
      immune activation. cART restricts the synthesis of infectious virus but does not
      curtail HIV-1 transcription and translation from either the integrated or
      unintegrated viral genomes in infected cells. All treated patients with full
      viral suppression actually have low-level viremia. More than 60% of treated
      individuals also develop minor HIV-1 -associated neurocognitive deficits (HAND)
      due to residual virus and immune activation. Thus, new therapeutic agents are
      needed to curtail HIV-1 transcription and residual virus. In this study,
      luteolin, a dietary supplement, profoundly reduced HIV-1 infection in reporter
      cells and primary lymphocytes. HIV-1inhibition by luteolin was independent of
      viral entry, as shown by the fact that wild-type and VSV-pseudotyped HIV-1
      infections were similarly inhibited. Luteolin was unable to inhibit viral reverse
      transcription. Luteolin had antiviral activity in a latent HIV-1 reactivation
      model and effectively ablated both clade-B- and -C -Tat-driven LTR
      transactivation in reporter assays but had no effect on Tat expression and its
      sub-cellular localization. We conclude that luteolin confers anti-HIV-1 activity
      at the Tat functional level. Given its biosafety profile and ability to cross the
      blood-brain barrier, luteolin may serve as a base flavonoid to develop potent
      anti-HIV-1 derivatives to complement cART.

PMID- 22140485
TI  - Alterations in the interleukin-1/interleukin-1 receptor antagonist balance
      modulate cardiac remodeling following myocardial infarction in the mouse.
AB  - BACKGROUND: Healing after acute myocardial infarction (AMI) is characterized by
      an intense inflammatory response and increased Interleukin-1 (IL-1) tissue
      activity. Genetically engineered mice lacking the IL-1 receptor (IL-1R1-/-, not
      responsive to IL-1) or the IL-1 receptor antagonist (IL-1Ra, enhanced response to
      IL-1) have an altered IL-1/IL-1Ra balance that we hypothesize modulates infarct
      healing and cardiac remodeling after AMI. METHODS: IL-1R1-/- and IL-1Ra-/- male
      mice and their correspondent wild-types (WT) were subjected to permanent coronary
      artery ligation or sham surgery. Infarct size (trichrome scar size), apoptotic
      cell death (TUNEL) and left ventricular (LV) dimensions and function
      (echocardiography) were measured prior to and 7 days after surgery. RESULTS: When
      compared with the corresponding WT, IL-1R1-/- mice had significantly smaller
      infarcts (-25%), less cardiomyocyte apoptosis (-50%), and reduced LV enlargement
      (LV end-diastolic diameter increase [LVEDD], -20%) and dysfunction (LV ejection
      fraction [LVEF] decrease, -50%), whereas IL-1Ra-/- mice had significantly larger
      infarcts (+75%), more apoptosis (5-fold increase), and more severe LV enlargement
      (LVEDD increase,+30%) and dysfunction (LVEF decrease, +70%)(all P values <0.05).
      CONCLUSIONS: An imbalance in IL-1/IL-1Ra signaling at the IL-1R1 level modulates
      the severity of cardiac remodeling after AMI in the mouse, with reduced IL-1R1
      signaling providing protection and unopposed IL-1R1 signaling providing harm.

PMID- 22140484
TI  - High-throughput sequencing of RNA silencing-associated small RNAs in olive (Olea
      europaea L.).
AB  - Small RNAs (sRNAs) of 20 to 25 nucleotides (nt) in length maintain genome
      integrity and control gene expression in a multitude of developmental and
      physiological processes. Despite RNA silencing has been primarily studied in
      model plants, the advent of high-throughput sequencing technologies has enabled
      profiling of the sRNA component of more than 40 plant species. Here, we used deep
      sequencing and molecular methods to report the first inventory of sRNAs in olive
      (Olea europaea L.). sRNA libraries prepared from juvenile and adult shoots
      revealed that the 24-nt class dominates the sRNA transcriptome and atypically
      accumulates to levels never seen in other plant species, suggesting an active
      role of heterochromatin silencing in the maintenance and integrity of its large
      genome. A total of 18 known miRNA families were identified in the libraries.
      Also, 5 other sRNAs derived from potential hairpin-like precursors remain as
      plausible miRNA candidates. RNA blots confirmed miRNA expression and suggested
      tissue- and/or developmental-specific expression patterns. Target mRNAs of
      conserved miRNAs were computationally predicted among the olive cDNA collection
      and experimentally validated through endonucleolytic cleavage assays. Finally, we
      use expression data to uncover genetic components of the miR156, miR172 and
      miR390/TAS3-derived trans-acting small interfering RNA (tasiRNA) regulatory
      nodes, suggesting that these interactive networks controlling developmental
      transitions are fully operational in olive.

PMID- 22140486
TI  - Endoplasmic reticulum remodeling tunes IP3-dependent Ca2+ release sensitivity.
AB  - The activation of vertebrate development at fertilization relies on IP3-dependent
      Ca2+ release, a pathway that is sensitized during oocyte maturation. This
      sensitization has been shown to correlate with the remodeling of the endoplasmic
      reticulum into large ER patches, however the mechanisms involved are not clear.
      Here we show that IP3 receptors within ER patches have a higher sensitivity to
      IP3 than those in the neighboring reticular ER. The lateral diffusion rate of IP3
      receptors in both ER domains is similar, and ER patches dynamically fuse with
      reticular ER, arguing that IP3 receptors exchange freely between the two ER
      compartments. These results suggest that increasing the density of IP3 receptors
      through ER remodeling is sufficient to sensitize IP3-dependent Ca2+ release.
      Mathematical modeling supports this concept of 'geometric sensitization' of IP3
      receptors as a population, and argues that it depends on enhanced Ca2+-dependent
      cooperativity at sub-threshold IP3 concentrations. This represents a novel
      mechanism of tuning the sensitivity of IP3 receptors through ER remodeling during
      meiosis.

PMID- 22140487
TI  - Persistent high burden of invasive pneumococcal disease in South African HIV
      infected adults in the era of an antiretroviral treatment program.
AB  - BACKGROUND: Highly active antiretroviral treatment (HAART) programs have been
      associated with declines in the burden of invasive pneumococcal disease (IPD) in
      industrialized countries. The aim of this study was to evaluate trends in IPD
      hospitalizations in HIV-infected adults in Soweto, South Africa, associated with
      up-scaling of the HAART program from 2003 to 2008. METHODS: Laboratory-confirmed
      IPD cases were identified from 2003 through 2008 through an existing surveillance
      program. The period 2003-04 was designated as the early-HAART era, 2005-06 as the
      intermediate-HAART era and 2007-08 as the established-HAART era. The incidence of
      IPD was compared between the early-HAART and established-HAART eras in HIV
      infected and-uninfected individuals. RESULTS: A total of 2,567 IPD cases among
      individuals older than 18 years were reported from 2003 through 2008. Overall
      incidence of IPD (per 100,000) did not change during the study period in HIV
      infected adults (207.4 cases in the early-HAART and 214.0 cases in the
      established-HAART era; p = 0.55). IPD incidence, actually increased 1.16-fold
      (95% CI: 1.01; 1.62) in HIV-infected females between the early-and established
      HAART eras (212.1 cases and 246.2 cases, respectively; p = 0.03). The incidence
      of IPD remained unchanged in HIV-uninfected adults across the three time periods.
      CONCLUSION: Despite a stable prevalence of HIV and the increased roll-out of
      HAART for treatment of AIDS patients in our setting, the burden of IPD has not
      decreased among HIV-infected adults. The study indicates a need for ongoing
      monitoring of disease and HAART program effectiveness to reduce opportunistic
      infections in African adults with HIV/AIDS, as well as the need to consider
      alternate strategies including pneumococcal conjugate vaccine immunization for
      the prevention of IPD in HIV-infected adults.

PMID- 22140488
TI  - The association of PNPLA3 variants with liver enzymes in childhood obesity is
      driven by the interaction with abdominal fat.
AB  - BACKGROUND AND AIMS: A polymorphism in adiponutrin/patatin-like phospholipase-3
      gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest
      genetic determinant of liver fat and ALT levels in adulthood and childhood
      obesity. Aims of this study were i) to analyse in a large group of obese children
      the role of the interaction of not-genetic factors such as BMI, waist
      circumference (W/Hr) and insulin resistance (HOMA-IR) in exposing the association
      between the I148M polymorphism and ALT levels and ii) to stratify the individual
      risk of these children to have liver injury on the basis of this gene-environment
      interaction. METHODS: 1048 Italian obese children were investigated.
      Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M
      variant genotyped. RESULTS: Children carrying the 148M allele showed higher ALT
      and AST levels (p = 0.000006 and p = 0.0002, respectively). Relationships between
      BMI-SDS, HOMA-IR and W/Hr with ALT were analysed in function of the different
      PNPLA3 genotypes. Children 148M homozygous showed a stronger correlation between
      ALT and W/Hr than those carrying the other genotypes (p: 0.0045) and, therefore,
      148M homozygotes with high extent of abdominal fat (W/Hr above 0.62) had the
      highest OR (4.9, 95% C. I. 3.2-7.8, p = 0.00001) to develop pathologic ALT.
      CONCLUSIONS: We have i) showed for the first time that the magnitude of the
      association of PNPLA3 with liver enzymes is driven by the size of abdominal fat
      and ii) stratified the individual risk to develop liver damage on the basis of
      the interaction between the PNPLA3 genotype and abdominal fat.

PMID- 22140489
TI  - Replication and virus-induced transcriptome of HAdV-5 in normal host cells versus
      cancer cells--differences of relevance for adenoviral oncolysis.
AB  - Adenoviruses (Ads), especially HAdV-5, have been genetically equipped with tumor
      restricted replication potential to enable applications in oncolytic cancer
      therapy. Such oncolytic adenoviruses have been well tolerated in cancer patients,
      but their anti-tumor efficacy needs to be enhanced. In this regard, it should be
      considered that cancer cells, dependent on their tissue of origin, can differ
      substantially from the normal host cells to which Ads are adapted by complex
      virus-host interactions. Consequently, viral replication efficiency, a key
      determinant of oncolytic activity, might be suboptimal in cancer cells.
      Therefore, we have analyzed both the replication kinetics of HAdV-5 and the virus
      induced transcriptome in human bronchial epithelial cells (HBEC) in comparison to
      cancer cells. This is the first report on genome-wide expression profiling of Ads
      in their native host cells. We found that E1A expression and onset of viral
      genome replication are most rapid in HBEC and considerably delayed in melanoma
      cells. In squamous cell lung carcinoma cells, we observed intermediate HAdV-5
      replication kinetics. Infectious particle production, viral spread and lytic
      activity of HAdV-5 were attenuated in melanoma cells versus HBEC. Expression
      profiling at the onset of viral genome replication revealed that HAdV-5 induced
      the strongest changes in the cellular transcriptome in HBEC, followed by lung
      cancer and melanoma cells. We identified prominent regulation of genes involved
      in cell cycle and DNA metabolism, replication and packaging in HBEC, which is in
      accord with the necessity to induce S phase for viral replication. Strikingly, in
      melanoma cells HAdV-5 triggered opposing regulation of said genes and, in
      contrast to lung cancer cells, no weak S phase induction was detected when using
      the E2F promoter as reporter. Our results provide a rationale for improving
      oncolytic adenoviruses either by adaptation of viral infection to target tumor
      cells or by modulating tumor cell functions to better support viral replication.

PMID- 22140490
TI  - Structural basis and kinetics of force-induced conformational changes of an
      alphaA domain-containing integrin.
AB  - BACKGROUND: Integrin alpha(L)beta2 (lymphocyte function-associated antigen, LFA
      1) bears force upon binding to its ligand intercellular adhesion molecule 1 (ICAM
      1) when a leukocyte adheres to vascular endothelium or an antigen presenting cell
      (APC) during immune responses. The ligand binding propensity of LFA-1 is related
      to its conformations, which can be regulated by force. Three conformations of the
      LFA-1 alphaA domain, determined by the position of its alpha7-helix, have been
      suggested to correspond to three different affinity states for ligand binding.
      METHODOLOGY/PRINCIPAL FINDINGS: The kinetics of the force-driven transitions
      between these conformations has not been defined and dynamically coupled to the
      force-dependent dissociation from ligand. Here we show, by steered molecular
      dynamics (SMD) simulations, that the alphaA domain was successively transitioned
      through three distinct conformations upon pulling the C-terminus of its alpha7
      helix. Based on these sequential transitions, we have constructed a mathematical
      model to describe the coupling between the alphaA domain conformational changes
      of LFA-1 and its dissociation from ICAM-1 under force. Using this model to
      analyze the published data on the force-induced dissociation of single LFA-1/ICAM
      1 bonds, we estimated the force-dependent kinetic rates of interstate transition
      from the short-lived to intermediate-lived and from intermediate-lived to long
      lived states. Interestingly, force increased these transition rates; hence
      activation of LFA-1 was accelerated by pulling it via an engaged ICAM-1.
      CONCLUSIONS/SIGNIFICANCE: Our study defines the structural basis for mechanical
      regulation of the kinetics of LFA-1 alphaA domain conformational changes and
      relates these simulation results to experimental data of force-induced
      dissociation of single LFA-1/ICAM-1 bonds by a new mathematical model, thus
      provided detailed structural and kinetic characterizations for force
      stabilization of LFA-1/ICAM-1 interaction.

PMID- 22140491
TI  - Sublingual immunization with M2-based vaccine induces broad protective immunity
      against influenza.
AB  - BACKGROUND: The ectodomain of matrix protein 2 (M2e) of influenza A virus is a
      rationale target antigen candidate for the development of a universal vaccine
      against influenza as M2e undergoes little sequence variation amongst human
      influenza A strains. Vaccine-induced M2e-specific antibodies (Abs) have been
      shown to display significant cross-protective activity in animal models. M2e
      based vaccine constructs have been shown to be more protective when administered
      by the intranasal (i.n.) route than after parenteral injection. However, i.n.
      administration of vaccines poses rare but serious safety issues associated with
      retrograde passage of inhaled antigens and adjuvants through the olfactory
      epithelium. In this study, we examined whether the sublingual (s.l.) route could
      serve as a safe and effective alternative mucosal delivery route for
      administering a prototype M2e-based vaccine. The mechanism whereby s.l.
      immunization with M2e vaccine candidate induces broad protection against
      infection with different influenza virus subtypes was explored. METHODS AND
      RESULTS: A recombinant M2 protein with three tandem copies of the M2e (3M2eC) was
      expressed in Escherichia coli. Parenteral immunizations of mice with 3M2eC
      induced high levels of M2e-specific serum Abs but failed to provide complete
      protection against lethal challenge with influenza virus. In contrast, s.l.
      immunization with 3M2eC was superior for inducing protection in mice. In the
      latter animals, protection was associated with specific Ab responses in the
      lungs. CONCLUSIONS: The results demonstrate that s.l. immunization with 3M2eC
      vaccine induced airway mucosal immune responses along with broad cross-protective
      immunity to influenza. These findings may contribute to the understanding of the
      M2-based vaccine approach to control epidemic and pandemic influenza infections.

PMID- 22140492
TI  - Mixed infection with cagA positive and cagA negative strains of Helicobacter
      pylori lowers disease burden in The Gambia.
AB  - BACKGROUND: The prevalence of Helicobacter pylori including strains with
      putatively virulent genotypes is high, whereas the H. pylori-associated disease
      burden is low, in Africa compared to developed countries. In this study, we
      investigated the prevalence of virulence-related H. pylori genotypes and their
      association with gastroduodenal diseases in The Gambia. METHODS AND FINDINGS: DNA
      extracted from biopsies and H. pylori cultures from 169 subjects with abdominal
      pain, dyspepsia or other gastroduodenal diseases were tested by PCR for H.
      pylori. The H. pylori positive samples were further tested for the cagA oncogene
      and vacA toxin gene. One hundred and twenty one subjects (71.6%) were H. pylori
      positive. The cagA gene and more toxigenic s1 and m1 alleles of the vacA gene
      were found in 61.2%, 76.9% and 45.5% respectively of Gambian patients harbouring
      H. pylori. There was a high prevalence of cagA positive strains in patients with
      overt gastric diseases than those with non-ulcerative dyspepsia (NUD) (p = 0.05);
      however, mixed infection by cagA positive and cagA negative strains was more
      common in patients with NUD compared to patients with gastric disease (24.5%
      versus 0%; p = 0.002). CONCLUSION: This study shows that the prevalence of H.
      pylori is high in dyspeptic patients in The Gambia and that many strains are of
      the putatively more virulent cagA+, vacAs1 and vacAm1 genotypes. This study has
      also shown significantly lower disease burden in Gambians infected with a mixture
      of cag-positive and cag-negative strains, relative to those containing only cag
      positive or only cag-negative strains, which suggests that harbouring both cag
      positive and cag-negative strains is protective.

PMID- 22140493
TI  - Underestimated effect sizes in GWAS: fundamental limitations of single SNP
      analysis for dichotomous phenotypes.
AB  - Complex diseases are often highly heritable. However, for many complex traits
      only a small proportion of the heritability can be explained by observed genetic
      variants in traditional genome-wide association (GWA) studies. Moreover, for some
      of those traits few significant SNPs have been identified. Single SNP association
      methods test for association at a single SNP, ignoring the effect of other SNPs.
      We show using a simple multi-locus odds model of complex disease that moderate to
      large effect sizes of causal variants may be estimated as relatively small effect
      sizes in single SNP association testing. This underestimation effect is most
      severe for diseases influenced by numerous risk variants. We relate the
      underestimation effect to the concept of non-collapsibility found in the
      statistics literature. As described, continuous phenotypes generated with linear
      genetic models are not affected by this underestimation effect. Since many GWA
      studies apply single SNP analysis to dichotomous phenotypes, previously reported
      results potentially underestimate true effect sizes, thereby impeding
      identification of true effect SNPs. Therefore, when a multi-locus model of
      disease risk is assumed, a multi SNP analysis may be more appropriate.

PMID- 22140494
TI  - FTO is expressed in neurones throughout the brain and its expression is unaltered
      by fasting.
AB  - Single-nucleotide polymorphisms in the first intron of the ubiquitously expressed
      FTO gene are associated with obesity. Although the physiological functions of FTO
      remain unclear, food intake is often altered when Fto expression levels are
      manipulated. Furthermore, deletion of FTO from neurones alone has a similar
      effect on food intake to deletion of FTO in all tissues. These results indicate
      that FTO expression in the brain is particularly important. Considerable focus
      has been placed on the dynamic regulation of Fto mRNA expression in the
      hypothalamus after short-term (16-48 hour) fasting, but results have been
      controversial. There are no studies that quantify FTO protein levels across the
      brain, and assess its alteration following short-term fasting. Using
      immunohistochemistry, we found that FTO protein is widely expressed in mouse
      brain, and present in the majority of neurones. Using quantitative Western
      blotting and RT-qPCR we show that FTO protein and mRNA levels in the
      hypothalamus, cerebellum and rostral brain are relatively uniform, and levels in
      the brain are higher than in skeletal muscles of the lower limbs. Fasting for 18
      hours does not alter the expression pattern, or levels, of FTO protein and mRNA.
      We further show that the majority of POMC neurones, which are critically involved
      in food intake regulation, also express FTO, but that the percentage of FTO
      positive POMC neurones is not altered by fasting. In summary, we find no evidence
      that Fto/FTO expression is regulated by short-term (18-hour) fasting. Thus, it is
      unlikely that the hunger and increased post-fasting food intake caused by such
      food deprivation is driven by alterations in Fto/FTO expression. The widespread
      expression of FTO in neurones also suggests that physiological studies of this
      protein should not be limited to the hypothalamus.

PMID- 22140495
TI  - Do Rapoport's rule, mid-domain effect or environmental factors predict
      latitudinal range size patterns of terrestrial mammals in China?
AB  - BACKGROUND: Explaining species range size pattern is a central issue in
      biogeography and macroecology. Although several hypotheses have been proposed,
      the causes and processes underlying range size patterns are still not clearly
      understood. In this study, we documented the latitudinal mean range size patterns
      of terrestrial mammals in China, and evaluated whether that pattern conformed to
      the predictions of the Rapoport's rule several analytical methods. We also
      assessed the influence of the mid-domain effect (MDE) and environmental factors
      on the documented range size gradient. METHODOLOGY/PRINCIPAL FINDINGS:
      Distributions of 515 terrestrial mammals and data on nine environmental variables
      were compiled. We calculated mean range size of the species in each 5 degrees 
      latitudinal band, and created a range size map on a 100 km*100 km quadrat system.
      We evaluated Rapoport's rule according to Steven's, mid-point, Pagel's and cross
      species methods. The effect of the MDE was tested based on a Monte Carlo
      simulation and linear regression. We used stepwise generalized linear models and
      correlation analyses to detect the impacts of mean climate condition, climate
      variability, ambient energy and topography on range size. The results of the
      Steven's, Pagel's and cross-species methods supported Rapoport's rule, whereas
      the mid-point method resulted in a hump-shaped pattern. Our range size map showed
      that larger mean latitudinal extents emerged in the mid-latitudes. We found that
      the MDE explained 80.2% of the range size variation, whereas, environmental
      factors accounted for <30% of that variation. CONCLUSIONS/SIGNIFICANCE:
      Latitudinal range size pattern of terrestrial mammals in China supported
      Rapoport's rule, though the extent of that support was strongly influenced by
      methodology. The critical factor underlying the observed gradient was the MDE,
      and the effects of climate, energy and topography were limited. The mean climate
      condition hypothesis, climate variability hypothesis, ambient energy hypotheses
      and topographical heterogeneity hypotheses were not supported.

PMID- 22140496
TI  - Computational analysis of the ESX-1 region of Mycobacterium tuberculosis:
      insights into the mechanism of type VII secretion system.
AB  - Type VII secretion system (T7SS) is a recent discovery in bacterial secretion
      systems. First identified in Mycobacterium tuberculosis, this secretion system
      has later been reported in organisms belonging to the Actinomycetales order and
      even to distant phyla like Firmicutes. The genome of M. tuberculosis H37Rv
      contains five gene clusters that have evolved through gene duplication events and
      include components of the T7SS secretion machinery. These clusters are called
      ESAT-6 secretion system (ESX) 1 through 5. Out of these, ESX-1 has been the most
      widely studied region because of its pathological importance. In spite of this,
      the overall mechanism of protein translocation through ESX-1 secretion machinery
      is not clearly understood. Specifically, the structural components contributing
      to the translocation through the mycomembrane have not been characterized yet. In
      this study, we have carried out a comprehensive in silico analysis of the genes
      known to be involved in ESX-1 secretion pathway and identified putative proteins
      having high probability to be associated with this particular pathway. Our study
      includes analysis of phylogenetic profiles, identification of domains,
      transmembrane helices, 3D folds, signal peptides and prediction of protein
      protein associations. Based on our analysis, we could assign probable novel
      functions to a few of the ESX-1 components. Additionally, we have identified a
      few proteins with probable role in the initial activation and formation of
      mycomembrane translocon of ESX-1 secretion machinery. We also propose a probable
      working model of T7SS involving ESX-1 secretion pathway.

PMID- 22140497
TI  - Diagnostic value of lumbar facet joint injection: a prospective triple cross-over
      study.
AB  - The diagnosis "lumbar facet syndrome" is common and often indicates severe lumbar
      spine surgery procedures. It is doubtful whether a painful facet joint (FJ) can
      be identified by a single FJ block. The aim of this study was to clarify the
      validity of a single and placebo controlled bilateral FJ blocks using local
      anesthetics. A prospective single blinded triple cross-over study was performed.
      60 patients (31 f, 29 m, mean age 53.2 yrs (22-73)) with chronic low back pain
      (mean pain persistance 31 months, 6 months of conservative treatment without
      success) admitted to a local orthopaedic department for surgical or conservative
      therapy of chronic LBP, were included in the study. Effect on pain reduction (10
      point rating scale) was measured. The 60 subjects were divided into six groups
      with three defined sequences of fluoroscopically guided bilateral monosegmental
      lumbar FJ test injections in "oblique needle" technique: verum-(local anaesthetic
      ), placebo-(sodium chloride-) and sham-injection. Carry-over and periodic effects
      were evaluated and a descriptive and statistical analysis regarding the
      effectiveness, difference and equality of the FJ injections and the different
      responses was performed. The results show a high rate of non-response, which
      documents the lack of reliable and valid predictors for a positive response
      towards FJ blocks. There was a high rate of placebo reactions noted, including
      subjects who previously or later reacted positively to verum injections.
      Equivalence was shown among verum vs. placebo and partly vs. sham also. With
      regard to test validity criteria, a single intraarticular FJ block with local
      anesthetics is not useful to detect the pain-responsible FJ and therefore is no
      valid and reliable diagostic tool to specify indication of lumbar spine surgery.
      Comparative FJ blocks with local anesthetics and placebo-controls have to be
      interpretated carefully also, because they solely give no proper diagnosis on FJ
      being main pain generator.

PMID- 22140498
TI  - Hospitalisation with infection, asthma and allergy in Kawasaki disease patients
      and their families: genealogical analysis using linked population data.
AB  - BACKGROUND: Kawasaki disease results from an abnormal immunological response to
      one or more infectious triggers. We hypothesised that heritable differences in
      immune responses in Kawasaki disease-affected children and their families would
      result in different epidemiological patterns of other immune-related conditions.
      We investigated whether hospitalisation for infection and asthma/allergy were
      different in Kawasaki disease-affected children and their relatives.
      METHODS/MAJOR FINDINGS: We used Western Australian population-linked health data
      from live births (1970-2006) to compare patterns of hospital admissions in
      Kawasaki disease cases, age- and sex-matched controls, and their relatives. There
      were 295 Kawasaki disease cases and 598 age- and sex-matched controls, with 1,636
      and 3,780 relatives, respectively. Compared to controls, cases were more likely
      to have been admitted at least once with an infection (cases, 150 admissions
      (50.8%) vs controls, 210 admissions (35.1%); odds ratio (OR) = 1.9, 95%
      confidence interval (CI) 1.4-2.6, P = 7.2*10-6), and with asthma/allergy (cases,
      49 admissions (16.6%) vs controls, 42 admissions (7.0%); OR = 2.6, 95% CI 1.7
      4.2, P = 1.3*10-5). Cases also had more admissions per person with infection
      (cases, median 2 admissions, 95% CI 1-5, vs controls, median 1 admission, 95% CI
      1-4, P = 1.09*10-5). The risk of admission with infection was higher in the first
      degree relatives of Kawasaki disease cases compared to those of controls, but the
      differences were not significant. CONCLUSION: Differences in the immune phenotype
      of children who develop Kawasaki disease may influence the severity of other
      immune-related conditions, with some similar patterns observed in relatives.
      These data suggest the influence of shared heritable factors in these families.

PMID- 22140499
TI  - Tolerance and safety evaluation in a large cohort of healthy infants fed an
      innovative prebiotic formula: a randomized controlled trial.
AB  - BACKGROUND: the addition of oligosaccharides to infant formula has been shown to
      mimic some of the beneficial effects of human milk. The aim of the study was to
      assess the tolerance and safety of a formula containing an innovative mixture of
      oligosaccharides in early infancy. METHODOLOGY/PRINCIPAL FINDINGS: this study was
      performed as a multi-center, randomized, double-blind, placebo-controlled trial
      including healthy term infants. Infants were recruited before the age of 8 weeks,
      either having started with formula feeding or being fully breast-fed
      (breastfeeding group). Formula-fed infants were randomized to feeding with a
      regular formula containing a mixture of neutral oligosaccharides and pectin
      derived acidic oligosaccharides (prebiotic formula group) or regular formula
      without oligosaccharides (control formula group). Growth, tolerance and adverse
      events were assessed at 8, 16, 24 and 52 weeks of age. The prebiotic and control
      groups showed similar mean weight, length and head circumference, skin fold
      thicknesses, arm circumference gains and stool frequency at each study point. As
      far as the anthropometric parameters are concerned, the prebiotic group and the
      control group did not attain the values shown by the breastfeeding group at any
      study point. The skin fold thicknesses assessed in the breastfeeding group at 8
      weeks were strikingly larger than those in formula fed infants, whereas at 52
      weeks were strikingly smaller. The stool consistency in the prebiotic group was
      softer than in the control group at 8, 16 and 24 weeks (p<0.001) and closer to
      that of the breastfeeding group. There was no difference in the incidence of
      adverse events between the two formula groups. CONCLUSIONS: our findings
      demonstrate the tolerability and the long term safety of a formula containing an
      innovative mixture of oligosaccharides in a large cohort of healthy infants.
      TRIAL REGISTRATION: drks-neu.uniklinik-freiburg.de DRKS 00000201.

PMID- 22140500
TI  - The role of palmitoylation in signalling, cellular trafficking and plasma
      membrane localization of protease-activated receptor-2.
AB  - Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR)
      activated by proteolytic cleavage of its amino terminal domain by trypsin-like
      serine proteases. This irreversible activation mechanism leads to rapid receptor
      desensitization by internalisation and degradation. We have explored the role of
      palmitoylation, the post-translational addition of palmitate, in PAR2 signalling,
      trafficking, cell surface expression and desensitization. Experiments using the
      palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is
      important in trafficking of PAR2 endogenously expressed by prostate cancer cell
      lines. This was supported by palmitate labelling using two approaches, which
      showed that PAR2 stably expressed by CHO-K1 cells is palmitoylated and that
      palmitoylation occurs on cysteine 361. Palmitoylation is required for optimal
      PAR2 signalling as Ca2+ flux assays indicated that in response to trypsin
      agonism, palmitoylation deficient PAR2 is ~9 fold less potent than wildtype
      receptor with a reduction of about 33% in the maximum signal induced via the
      mutant receptor. Confocal microscopy, flow cytometry and cell surface
      biotinylation analyses demonstrated that palmitoylation is required for efficient
      cell surface expression of PAR2. We also show that receptor palmitoylation occurs
      within the Golgi apparatus and is required for efficient agonist-induced rab11a
      mediated trafficking of PAR2 to the cell surface. Palmitoylation is also required
      for receptor desensitization, as agonist-induced beta-arrestin recruitment and
      receptor endocytosis and degradation were markedly reduced in CHO-PAR2-C361A
      cells compared with CHO-PAR2 cells. These data provide new insights on the life
      cycle of PAR2 and demonstrate that palmitoylation is critical for efficient
      signalling, trafficking, cell surface localization and degradation of this
      receptor.

PMID- 22140501
TI  - A knockout mutation of a constitutive GPCR in Tetrahymena decreases both G
      protein activity and chemoattraction.
AB  - Although G-protein coupled receptors (GPCRs) are a common element in many
      chemosensory transduction pathways in eukaryotic cells, no GPCR or regulated G
      protein activity has yet been shown in any ciliate. To study the possible role
      for a GPCR in the chemoresponses of the ciliate Tetrahymena, we have generated a
      number of macronuclear gene knockouts of putative GPCRs found in the Tetrahymena
      Genome database. One of these knockout mutants, called G6, is a complete knockout
      of a gene that we call GPCR6 (TTHERM_00925490). Based on sequence comparisons,
      the Gpcr6p protein belongs to the Rhodopsin Family of GPCRs. Notably, Gpcr6p
      shares highest amino acid sequence homologies to GPCRs from Paramecium and
      several plants. One of the phenotypes of the G6 mutant is a decreased
      responsiveness to the depolarizing ions Ba2+ and K+, suggesting a decrease in
      basal excitability (decrease in Ca2+ channel activity). The other major phenotype
      of G6 is a loss of chemoattraction to lysophosphatidic acid (LPA) and proteose
      peptone (PP), two known chemoattractants in Tetrahymena. Using microsomal
      [35S]GTPgammaS binding assays, we found that wild-type (CU427) have a prominent
      basal G-protein activity. This activity is decreased to the same level by
      pertussis toxin (a G-protein inhibitor), addition of chemoattractants, or the G6
      mutant. Since the basal G-protein activity is decreased by the GPCR6 knockout, it
      is likely that this gene codes for a constitutively active GPCR in Tetrahymena.
      We propose that chemoattractants like LPA and PP cause attraction in Tetrahymena
      by decreasing the basal G-protein stimulating activity of Gpcr6p. This leads to
      decreased excitability in wild-type and longer runs of smooth forward swimming
      (less interrupted by direction changes) towards the attractant. Therefore, these
      attractants may work as inverse agonists through the constitutively active Gpcr6p
      coupled to a pertussis-sensitive G-protein.

PMID- 22140502
TI  - Integrating personality research and animal contest theory: aggressiveness in the
      green swordtail Xiphophorus helleri.
AB  - Aggression occurs when individuals compete over limiting resources. While
      theoretical studies have long placed a strong emphasis on context-specificity of
      aggression, there is increasing recognition that consistent behavioural
      differences exist among individuals, and that aggressiveness may be an important
      component of individual personality. Though empirical studies tend to focus on
      one aspect or the other, we suggest there is merit in modelling both within- and
      among-individual variation in agonistic behaviour simultaneously. Here, we
      demonstrate how this can be achieved using multivariate linear mixed effect
      models. Using data from repeated mirror trials and dyadic interactions of male
      green swordtails, Xiphophorus helleri, we show repeatable components of
      (co)variation in a suite of agonistic behaviour that is broadly consistent with a
      major axis of variation in aggressiveness. We also show that observed focal
      behaviour is dependent on opponent effects, which can themselves be repeatable
      but were more generally found to be context specific. In particular, our models
      show that within-individual variation in agonistic behaviour is explained, at
      least in part, by the relative size of a live opponent as predicted by contest
      theory. Finally, we suggest several additional applications of the multivariate
      models demonstrated here. These include testing the recently queried functional
      equivalence of alternative experimental approaches, (e.g., mirror trials, dyadic
      interaction tests) for assaying individual aggressiveness.

PMID- 22140503
TI  - Identifying individuals at risk for fracture in Guatemala.
AB  - INTRODUCTION: The FRAX calculator combines a set of clinical risk factors with
      country-specific incidence rates to determine the ten-year absolute risk of major
      osteoporotic fracture. However, regional or country-specific databases from
      Central American countries are not available. We compared the use of various FRAX
      databases and the Pluijm algorithm in determining risk of fracture. METHODS: We
      collected clinical risk factor data needed for the FRAX calculator and Pluijm
      algorithm of Hispanic women in Guatemala and calculated the FRAX absolute risk
      measures of major osteoporotic fracture and hip fracture. Subjects were
      postmenopausal women greater than age 40 with no history of using medication that
      affect bone. A random sample of 204 women in 34 different regions women in
      Guatemala City was visited in their homes to complete the surveys. The Pluijm
      risk score and FRAX risk score using the US Hispanic, Spain, and Mexican
      databases were calculated. RESULTS: We used the US NOF guidelines for treatment
      which suggest a treatment threshold for patients with a 10-year hip fracture
      probability >= 3% or a 10-year major osteoporotic fracture risk >= 20%. The
      number of patients meeting the suggested threshold limits for treatment using the
      Spain and Mexico calculators were identical. There was 100% conformity in
      threshold limits for both hip and major osteoporotic fracture risk. The mean
      conformity for any fracture risk between US Hispanic and the other two databases
      was 97.5%. Conformity was 99.0% based on major osteoporotic fracture and 97.5%
      based on risk of hip fracture. The Pluijm evaluation shows conformity of 87.2%
      and 83.3%, respectively, when compared to the US Hispanic and Spain/Mexico FRAX
      thresholds for risk of fracture. DISCUSSION: Although the different FRAX
      databases provide variations in the absolute risk of fracture, the overall
      conformity to treatment thresholds amongst the US Hispanic, Spain, and Mexico
      databases show the database used would have little effect as to the decision to
      treat. The Pluijm tool conforms to the FRAX thresholds and can be used as well.
      It does not matter which country-specific calculator or assessment tool is used,
      as there are a similar number of patients that would meet the intervention
      threshold.

PMID- 22140504
TI  - The effects of biogeography on ant diversity and activity on the Boston Harbor
      Islands, Massachusetts, U.S.A.
AB  - Many studies have examined how island biogeography affects diversity on the scale
      of island systems. In this study, we address how diversity varies over very short
      periods of time on individual islands. To do this, we compile an inventory of the
      ants living in the Boston Harbor Islands National Recreation Area, Boston,
      Massachusetts, USA using data from a five-year All Taxa Biodiversity Inventory of
      the region's arthropods. Consistent with the classical theory of island
      biogeography, species richness increased with island size, decreased with island
      isolation, and remained relatively constant over time. Additionally, our
      inventory finds that almost half of the known Massachusetts ant fauna can be
      collected in the BHI, and identifies four new species records for Massachusetts,
      including one new to the United States, Myrmica scabrinodis. We find that the
      number of species actually active on islands depended greatly on the timescale
      under consideration. The species that could be detected during any given week of
      sampling could by no means account for total island species richness, even when
      correcting for sampling effort. Though we consistently collected the same number
      of species over any given week of sampling, the identities of those species
      varied greatly between weeks. This variation does not result from local
      immigration and extinction of species, nor from seasonally-driven changes in the
      abundance of individual species, but rather from weekly changes in the
      distribution and activity of foraging ants. This variation can be upwards of 50%
      of ant species per week. This suggests that numerous ant species on the BHI share
      the same physical space at different times. This temporal partitioning could well
      explain such unexpectedly high ant diversity in an isolated, urban site.

PMID- 22140505
TI  - Altered insulin receptor signalling and beta-cell cycle dynamics in type 2
      diabetes mellitus.
AB  - Insulin resistance, reduced beta-cell mass, and hyperglucagonemia are consistent
      features in type 2 diabetes mellitus (T2DM). We used pancreas and islets from
      humans with T2DM to examine the regulation of insulin signaling and cell-cycle
      control of islet cells. We observed reduced beta-cell mass and increased alpha
      cell mass in the Type 2 diabetic pancreas. Confocal microscopy, real-time PCR and
      western blotting analyses revealed increased expression of PCNA and down
      regulation of p27-Kip1 and altered expression of insulin receptors, insulin
      receptor substrate-2 and phosphorylated BAD. To investigate the mechanisms
      underlying these findings, we examined a mouse model of insulin resistance in
      beta-cells--which also exhibits reduced beta-cell mass, the beta-cell-specific
      insulin receptor knockout (betaIRKO). Freshly isolated islets and beta-cell lines
      derived from betaIRKO mice exhibited poor cell-cycle progression, nuclear
      restriction of FoxO1 and reduced expression of cell-cycle proteins favoring
      growth arrest. Re-expression of insulin receptors in betaIRKO beta-cells reversed
      the defects and promoted cell cycle progression and proliferation implying a role
      for insulin-signaling in beta-cell growth. These data provide evidence that human
      beta- and alpha-cells can enter the cell-cycle, but proliferation of beta-cells
      in T2DM fails due to G1-to-S phase arrest secondary to defective insulin
      signaling. Activation of insulin signaling, FoxO1 and proteins in beta-cell-cycle
      progression are attractive therapeutic targets to enhance beta-cell regeneration
      in the treatment of T2DM.

PMID- 22140506
TI  - CD133/Src axis mediates tumor initiating property and epithelial-mesenchymal
      transition of head and neck cancer.
AB  - BACKGROUND: Head and Neck squamous cell carcinoma (HNSCC) is a human lethal
      cancer with clinical, pathological, phenotypical and biological heterogeneity.
      Caner initiating cells (CICs), which are responsible for tumor growth and coupled
      with gain of epithelial-mesenchymal transition (EMT), have been identified.
      Previously, we enriched a subpopulation of head and neck cancer initiating cells
      (HN-CICs) with up-regulation of CD133 and enhancement of EMT. Others demonstrate
      that Src kinase interacts with and phosphorylates the cytoplasmic domain of
      CD133. However, the physiological function of CD133/Src signaling in HNSCCs has
      not been uncovered. METHODOLOGY/PRINCIPAL FINDING: Herein, we determined the
      critical role of CD133/Src axis modulating stemness, EMT and tumorigenicity of
      HNSCC and HN-CICs. Initially, down-regulation of CD133 significantly reduced the
      self-renewal ability and expression of stemness genes, and promoted the
      differentiation and apoptotic capability of HN-CICs. Additionally, knockdown of
      CD133 in HN-CICs also lessened both in vitro malignant properties including cell
      migration/cell invasiveness/anchorage independent growth, and in vivo tumor
      growth by nude mice xenotransplantation assay. In opposite, overexpression of
      CD133 enhanced the stemness properties and tumorigenic ability of HNSCCs. Lastly,
      up-regulation of CD133 increased phosphorylation of Src coupled with EMT
      transformation in HNSCCs, on the contrary, silence of CD133 or treatment of Src
      inhibitor inversely abrogated above phenotypic effects, which were induced by
      CD133 up-regulation in HNSCCs or HN-CICs. CONCLUSION/SIGNIFICANCE: Our results
      suggested that CD133/Src signaling is a regulatory switch to gain of EMT and of
      stemness properties in HNSCC. Finally, CD133/Src axis might be a potential
      therapeutic target for HNSCC by eliminating HN-CICs.

PMID- 22140507
TI  - Risk factors for chronic cerebrospinal venous insufficiency (CCSVI) in a large
      cohort of volunteers.
AB  - BACKGROUND: The role of intra- and extra-cranial venous system impairment in the
      pathogenesis of various vascular, inflammatory and neurodegenerative neurological
      disorders, as well as in aging, has not been studied in detail. Nor have risk
      factors been determined for increased susceptibility of venous pathology in the
      intra-cranial and extra-cranial veins. The aim of this study was to investigate
      the association between presence of a newly proposed vascular condition called
      chronic cerebrospinal venous insufficiency (CCSVI) and environmental factors in a
      large volunteer control group without known central nervous system pathology.
      METHODS AND FINDINGS: The data were collected in a prospective study from 252
      subjects who were screened for medical history as part of the entry criteria and
      participated in the case-control study of CCSVI prevalence in multiple sclerosis
      (MS) patients, and then were analyzed post-hoc. All participants underwent
      physical and Doppler sonography examinations, and were assessed with a structured
      environmental questionnaire. Fullfilment of >= 2 positive venous hemodynamic (VH)
      criteria on Doppler sonography was considered indicative of CCSVI diagnosis. Risk
      and protective factors associated with CCSVI were analyzed using logistic
      regression analysis. Seventy (27.8%) subjects presented with CCSVI diagnosis and
      153 (60.7%) presented with one or more VH criteria. The presence of heart disease
      (p = .001), especially heart murmurs (p = .007), a history of infectious
      mononucleosis (p = .002), and irritable bowel syndrome (p = .005) were associated
      with more frequent CCSVI diagnosis. Current or previous smoking (p = .029) showed
      a trend for association with more frequent CCSVI diagnosis, while use of dietary
      supplements (p = .018) showed a trend for association with less frequent CCSVI
      diagnosis. CONCLUSIONS: Risk factors for CCSVI differ from established risk
      factors for peripheral venous diseases. Vascular, infectious and inflammatory
      factors were associated with higher CCSVI frequency.

PMID- 22140508
TI  - Docosahexaenoic acid inhibits UVB-induced activation of NF-kappaB and expression
      of COX-2 and NOX-4 in HR-1 hairless mouse skin by blocking MSK1 signaling.
AB  - Exposure to ultraviolet-B (UVB) radiation induces inflammation and
      photocarcinogenesis in mammalian skin. Docosahexaenoic acid (DHA), a
      representative omega-3 polyunsaturated fatty acid, has been reported to possess
      anti-inflammatory and chemopreventive properties. In the present study, we
      investigated the molecular mechanisms underlying the inhibitory effects of DHA on
      UVB-induced inflammation in mouse skin. Our study revealed that topical
      application of DHA prior to UVB irradiation attenuated the expression of
      cyclooxygenase-2 (COX-2) and NAD(P)H:oxidase-4 (NOX-4) in hairless mouse skin.
      DHA pretreatment also attenuated UVB-induced DNA binding of nuclear factor-kappaB
      (NF-kappaB) through the inhibition of phosphorylation of IkappaB kinase
      alpha/beta, phosphorylation and degradation of IkappaBalpha and nuclear
      translocation of p50 and p65. In addition, UVB-induced phosphorylation of p65 at
      the serine 276 residue was significantly inhibited by topical application of DHA.
      Irradiation with UVB induced phosphorylation of mitogen and stress-activated
      kinase-1 (MSK1), extracellular signal-regulated kinase (ERK) and p38 mitogen
      activated protein (MAP) kinase, and all these events were attenuated by
      pretreatment with DHA. Blocking ERK and p38 MAP kinase signaling by U0126 and
      SB203580, respectively, diminished MSK1 phosphorylation in UVB-irradiated mouse
      skin. Pretreatment with H-89, a pharmacological inhibitor of MSK1, abrogated UVB
      induced activation of NF-kappaB and the expression of COX-2 and NOX-4 in mouse
      skin. In conclusion, topically applied DHA inhibits the UVB-induced activation of
      NF-kappaB and the expression of COX-2 and NOX-4 by blocking the phosphorylation
      of MSK1, a kinase downstream of ERK and p38 MAP kinase, in hairless mouse skin.

PMID- 22140509
TI  - Oryza sativa cytochrome P450 family member OsCYP96B4 reduces plant height in a
      transcript dosage dependent manner.
AB  - BACKGROUND: Plant cytochromes P450 are involved in a wide range of biosynthetic
      reactions and play various roles in plant development. However, little is known
      about the biological functions of the subfamily CYP96 in plants.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a novel semi-dwarf rice mutant,
      in which a single copy of transposon dissociator (Ds) was inserted into the gene
      OsCYP96B4 (Oryza sativa Cytochrome P450 96B4). The mutant exhibits the defects in
      cell elongation and pollen germination, which can be complemented by the wild
      type OsCYP96B4 and be rescued by remobilization of the Ds element with the
      presence of the transposase Activator (Ac). Transgenic plants harboring OsCYP96B4
      double-stranded RNA interference construct mimicked the mutant phenotype. The
      oscyp96b4 mutant phenotype could not be rescued by all the tested phytohormones
      and it was found that OsCYP96B4 reduced plant height in a transcript dosage
      dependent manner. Heterologous expression of OsCYP96B4 in Schizosaccharomyces
      pombe resulted in missegregation and wider cells. Further investigation showed
      that the mutant exhibited the defects in the metabolism of some lipid molecular
      species when compared with the wild type. CONCLUSIONS/SIGNIFICANCE: The oscyp96b4
      mutant is a novel rice semi-dwarf mutant. Our data suggest that OsCYP96B4 might
      be involved in lipid metabolism and regulate cell elongation.

PMID- 22140510
TI  - Inhibition of Hedgehog signaling antagonizes serous ovarian cancer growth in a
      primary xenograft model.
AB  - BACKGROUND: Recent evidence links aberrant activation of Hedgehog (Hh) signaling
      with the pathogenesis of several cancers including medulloblastoma, basal cell,
      small cell lung, pancreatic, prostate and ovarian. This investigation was
      designed to determine if inhibition of this pathway could inhibit serous ovarian
      cancer growth. METHODOLOGY: We utilized an in vivo pre-clinical model of serous
      ovarian cancer to characterize the anti-tumor activity of Hh pathway inhibitors
      cyclopamine and a clinically applicable derivative, IPI-926. Primary human serous
      ovarian tumor tissue was used to generate tumor xenografts in mice that were
      subsequently treated with cyclopamine or IPI-926. PRINCIPAL FINDINGS: Both
      compounds demonstrated significant anti-tumor activity as single agents. When IPI
      926 was used in combination with paclitaxel and carboplatinum (T/C), no
      synergistic effect was observed, though sustained treatment with IPI-926 after
      cessation of T/C continued to suppress tumor growth. Hh pathway activity was
      analyzed by RT-PCR to assess changes in Gli1 transcript levels. A single dose of
      IPI-926 inhibited mouse stromal Gli1 transcript levels at 24 hours with unchanged
      human intra-tumor Gli1 levels. Chronic IPI-926 therapy for 21 days, however,
      inhibited Hh signaling in both mouse stromal and human tumor cells. Expression
      data from the micro-dissected stroma in human serous ovarian tumors confirmed the
      presence of Gli1 transcript and a significant association between elevated Gli1
      transcript levels and worsened survival. CONCLUSIONS/SIGNIFICANCE: IPI-926
      treatment inhibits serous tumor growth suggesting the Hh signaling pathway
      contributes to the pathogenesis of ovarian cancer and may hold promise as a novel
      therapeutic target, especially in the maintenance setting.

PMID- 22140511
TI  - Linking fearfulness and coping styles in fish.
AB  - Consistent individual differences in cognitive appraisal and emotional
      reactivity, including fearfulness, are important personality traits in humans,
      non-human mammals, and birds. Comparative studies on teleost fishes support the
      existence of coping styles and behavioral syndromes also in poikilothermic
      animals. The functionalist approach to emotions hold that emotions have evolved
      to ensure appropriate behavioral responses to dangerous or rewarding stimuli.
      Little information is however available on how evolutionary widespread these
      putative links between personality and the expression of emotional or affective
      states such as fear are. Here we disclose that individual variation in coping
      style predicts fear responses in Nile tilapia Oreochromis niloticus, using the
      principle of avoidance learning. Fish previously screened for coping style were
      given the possibility to escape a signalled aversive stimulus. Fearful
      individuals showed a range of typically reactive traits such as slow recovery of
      feed intake in a novel environment, neophobia, and high post-stress cortisol
      levels. Hence, emotional reactivity and appraisal would appear to be an essential
      component of animal personality in species distributed throughout the vertebrate
      subphylum.

PMID- 22140512
TI  - Congenital cataract causing mutants of alphaA-crystallin/sHSP form aggregates and
      aggresomes degraded through ubiquitin-proteasome pathway.
AB  - BACKGROUND: Mutations of human alphaA-crystallin cause congenital cataract by
      protein aggregation. How mutations of alphaA-crystallin cause disease
      pathogenesis through protein aggregation is not well understood. To better
      understand the cellular events leading to protein aggregation, we transfected
      cataract causing mutants, R12C, R21L, R21W, R49C, R54C, R116C and R116H, of human
      alphaA-crystallin in HeLa cells and examined the formation of intracellular
      protein aggregates and aggresomes by confocal microscopy. METHODOLOGY/PRINCIPAL
      FINDINGS: YFP-tagged human alphaA-wild-type (alphaA-wt) was sub-cloned and the
      mutants were generated by site-directed mutagenesis. The alphaA-wt and the
      mutants were individually transfected or co-transfected with CFP-tagged alphaA-wt
      or alphaB-wild-type (alphaB-wt) in HeLa cells. Overexpression of these mutants
      forms multiple small dispersed cytoplasmic aggregates as well as aggresomes. Co
      expression of alphaB-wt with these mutants significantly inhibited protein
      aggregates where as co-expression with alphaA-wt enhanced protein aggregates
      which seems to be due to co-aggregation of the mutants with alphaA-wt. Aggresomes
      were validated by double immunofluorescence by co-localization of gamma-tubulin,
      a centrosome marker protein with alphaA-crystallin. Furthermore, increased
      ubiquitination was detected in R21W, R116C and R116H as assessed by western blot
      analyses. Immunostaining with an ubiquitin antibody revealed that ubiquitin
      inclusions in the perinuclear regions were evident only in R116C transfected
      cells. Pulse chase assay, after cycloheximide treatment, suggested that R116C
      degraded faster than the wild-type control. CONCLUSIONS/SIGNIFICANCE: Mutants of
      alphaA-crystallin form aggregates and aggresomes. Co-expression of alphaA-wt with
      the mutants increased aggregates and co-expression of alphaB-wt with the mutants
      significantly decreased the aggregates. The mutant, R116C protein degraded faster
      than wild-type control and increased ubiquitination was evident in R116C
      expressing cells.

PMID- 22140513
TI  - dp53 Restrains ectopic neural stem cell formation in the Drosophila brain in a
      non-apoptotic mechanism involving Archipelago and cyclin E.
AB  - Accumulating evidence suggests that tumor-initiating stem cells or cancer stem
      cells (CSCs) possibly originating from normal stem cells may be the root cause of
      certain malignancies. How stem cell homeostasis is impaired in tumor tissues is
      not well understood, although certain tumor suppressors have been implicated. In
      this study, we use the Drosophila neural stem cells (NSCs) called neuroblasts as
      a model to study this process. Loss-of-function of Numb, a key cell fate
      determinant with well-conserved mammalian counterparts, leads to the formation of
      ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of
      the Drosophila tumor suppressor p53 (dp53) was able to suppress ectopic
      neuroblast formation caused by numb loss-of-function. This occurred in a non
      apoptotic manner and was independent of Dacapo, the fly counterpart of the well
      characterized mammalian p53 target p21 involved in cellular senescence. The
      observation that dp53 affected Edu incorporation into neuroblasts led us to test
      the hypothesis that dp53 acts through regulation of factors involved in cell
      cycle progression. Our results show that the inhibitory effect of dp53 on ectopic
      neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc
      E). Overexpression of Cyc E was able to abrogate dp53's ability to rescue numb
      loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago
      (Ago), a recently identified transcriptional target of dp53 and a negative
      regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by
      overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our
      results reveal an intimate connection between cell cycle progression and NSC self
      renewal vs. differentiation control, and indicate that p53-mediated regulation of
      ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly
      important when NSC homeostasis is perturbed as in numb loss-of-function
      condition. This has important clinical implications.

PMID- 22140514
TI  - Internet-based CBT for depression with and without telephone tracking in a
      national helpline: randomised controlled trial.
AB  - BACKGROUND: Telephone helplines are frequently and repeatedly used by individuals
      with chronic mental health problems and web interventions may be an effective
      tool for reducing depression in this population. AIM: To evaluate the
      effectiveness of a 6 week, web-based cognitive behaviour therapy (CBT)
      intervention with and without proactive weekly telephone tracking in the
      reduction of depression in callers to a helpline service. METHOD: 155 callers to
      a national helpline service with moderate to high psychological distress were
      recruited and randomised to receive either Internet CBT plus weekly telephone
      follow-up; Internet CBT only; weekly telephone follow-up only; or treatment as
      usual. RESULTS: Depression was lower in participants in the web intervention
      conditions both with and without telephone tracking compared to the treatment as
      usual condition both at post intervention and at 6 month follow-up. Telephone
      tracking provided by a lay telephone counsellor did not confer any additional
      advantage in terms of symptom reduction or adherence. CONCLUSIONS: A web-based
      CBT program is effective both with and without telephone tracking for reducing
      depression in callers to a national helpline. TRIAL REGISTRATION: Controlled
      Trials.comISRCTN93903959.

PMID- 22140515
TI  - On the evolutionary origin of eukaryotic DNA methyltransferases and Dnmt2.
AB  - The Dnmt2 enzymes show strong amino acid sequence similarity with eukaryotic and
      prokaryotic DNA-(cytosine C5)-methyltransferases. Yet, Dnmt2 enzymes from several
      species were shown to methylate tRNA-Asp and had been proposed that eukaryotic
      DNA methyltransferases evolved from a Dnmt2-like tRNA methyltransferase ancestor
      [Goll et al., 2006, Science, 311, 395-8]. It was the aim of this study to
      investigate if this hypothesis could be supported by evidence from sequence
      alignments. We present phylogenetic analyses based on sequence alignments of the
      methyltransferase catalytic domains of more than 2300 eukaryotic and prokaryotic
      DNA-(cytosine C5)-methyltransferases and analyzed the distribution of DNA
      methyltransferases in eukaryotic species. The Dnmt2 homologues were reliably
      identified by an additional conserved CFT motif next to motif IX. All DNA
      methyltransferases and Dnmt2 enzymes were clearly separated from other RNA
      (cytosine-C5)-methyltransferases. Our sequence alignments and phylogenetic
      analyses indicate that the last universal eukaryotic ancestor contained at least
      one member of the Dnmt1, Dnmt2 and Dnmt3 families of enzymes and additional RNA
      methyltransferases. The similarity of Dnmt2 enzymes with DNA methyltransferases
      and absence of similarity with RNA methyltransferases combined with their strong
      RNA methylation activity suggest that the ancestor of Dnmt2 was a DNA
      methyltransferase and an early Dnmt2 enzyme changed its substrate preference to
      tRNA. There is no phylogenetic evidence that Dnmt2 was the precursor of
      eukaryotic Dnmts. Most likely, the eukaryotic Dnmt1 and Dnmt3 families of DNA
      methyltransferases had an independent origin in the prokaryotic DNA
      methyltransferase sequence space.

PMID- 22140516
TI  - Novel inhibitor design for hemagglutinin against H1N1 influenza virus by core
      hopping method.
AB  - The worldwide spread of H1N1 avian influenza and the increasing reports about its
      resistance to the current drugs have made a high priority for developing new anti
      influenza drugs. Owing to its unique function in assisting viruses to bind the
      cellular surface, a key step for them to subsequently penetrate into the infected
      cell, hemagglutinin (HA) has become one of the main targets for drug design
      against influenza virus. To develop potent HA inhibitors, the ZINC fragment
      database was searched for finding the optimal compound with the core hopping
      technique. As a result, the Neo6 compound was obtained. It has been shown through
      the subsequent molecular docking studies and molecular dynamic simulations that
      Neo6 not only assumes more favorable conformation at the binding pocket of HA but
      also has stronger binding interaction with its receptor. Accordingly, Neo6 may
      become a promising candidate for developing new and more powerful drugs for
      treating influenza. Or at the very least, the findings reported here may provide
      useful insights to stimulate new strategy in this area.

PMID- 22140517
TI  - Ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in
      Vietnamese patients.
AB  - Human Ficolin-2 (L-ficolins) encoded by FCN2 gene is a soluble serum protein that
      plays an important role in innate immunity and is mainly expressed in the liver.
      Ficolin-2 serum levels and FCN2 single nucleotide polymorphisms were associated
      to several infectious diseases. We initially screened the complete FCN2 gene in
      48 healthy individuals of Vietnamese ethnicity. We genotyped a Vietnamese cohort
      comprising of 423 clinically classified hepatitis B virus patients and 303
      controls for functional single nucleotide polymorphisms in the promoter region (
      986G>A, -602G>A, -4A>G) and in exon 8 (+6424G>T) by real-time PCR and
      investigated the contribution of FCN2 genotypes and haplotypes to serum Ficolin-2
      levels, viral load and liver enzyme levels. Haplotypes differed significantly
      between patients and controls (P = 0.002) and the haplotype AGGG was found
      frequently in controls in comparison to patients with hepatitis B virus and
      hepatocellular carcinoma (P = 0.0002 and P<0.0001) conferring a protective
      effect. Ficolin-2 levels differed significantly between patients and controls
      (p<0.0001). Patients with acute hepatitis B had higher serum Ficolin-2 levels
      compared to other patient groups and controls.The viral load was observed to be
      significantly distributed among the haplotypes (P = 0.04) and the AAAG haplotype
      contributed to higher Ficolin-2 levels and to viral load. Four novel single
      nucleotide polymorphisms in introns (-941G>T, -310G>A, +2363G>A, +4882G>A) and
      one synonymous mutation in exon 8 (+6485G>T) was observed. Strong linkage was
      found between the variant -986G>A and -4A>G. The very first study on Vietnamese
      cohort associates both Ficolin-2 serum levels and FCN2 haplotypes to hepatitis B
      virus infection and subsequent disease progression.

PMID- 22140518
TI  - Production of dsRNA sequences in the host plant is not sufficient to initiate
      gene silencing in the colonizing oomycete pathogen Phytophthora parasitica.
AB  - Species of the oomycete genus Phytophthora are destructive pathogens, causing
      extensive losses in agricultural crops and natural ecosystems. A potential
      disease control approach is the application of RNA silencing technology which has
      proven to be effective in improving plant resistance against a wide range of
      pests including parasitic plants, nematodes, insects and fungi. In this study, we
      tested the potential application of RNA silencing in improving plant disease
      resistance against oomycete pathogens. The endogenous P. parasitica gene PnPMA1
      and the reporter gene GFP were used to evaluate the potential application of host
      induced gene silencing (HIGS). The GFP-expressing P. parasitica efficiently
      colonized Arabidopsis thaliana lines stably expressing GFP dsRNA and showed no
      obvious decrease in GFP signal intensity. Quantitative RT-PCR analyses showed no
      significant reductions in the abundance of GFP and PnPMA1 transcripts in P.
      parasitica during colonization of A. thaliana lines stably expressing GFP and
      PnPMA1 dsRNAs, respectively. Neither GFP siRNAs nor PnPMA1 siRNAs produced by
      transgenic plants were detected in P. parasitica re-isolated from infected
      tissues by Northern blot analyses. Phenotypic characterization of zoospores
      released from infected plant roots expressing PnPMA1 dsRNA showed no motility
      changes compared with those from wild-type plants. Similar results were obtained
      by analysis of zoospores released from sporulating hyphae of P. parasitica re
      isolated from PnPMA1 dsRNA-expressing plant roots. Thus, the ectopic expression
      of dsRNA sequences in the host plant is not sufficient to initiate silencing of
      homologous genes in the colonizing oomycete pathogen, and this may be due to a
      number of different reasons including the absence of genetic machinery required
      for uptake of silencing signals in particular dsRNAs which are essential for
      environmental RNA silencing.

PMID- 22140519
TI  - Identification of a TPX2-like microtubule-associated protein in Drosophila.
AB  - Chromosome segregation during mitosis and meiosis relies on the spindle and the
      functions of numerous microtubule-associated proteins (MAPs). One of the best
      studied spindle MAPs is the highly conserved TPX2, which has been reported to
      have characteristic intracellular dynamics and molecular activities, such as
      nuclear localisation in interphase, poleward movement in the metaphase spindle,
      microtubule nucleation, microtubule stabilisation, microtubule bundling, Aurora A
      kinase activation, kinesin-5 binding, and kinesin-12 recruitment. This protein
      has been shown to be essential for spindle formation in every cell type analysed
      so far. However, as yet, TPX2 homologues have not been found in the Drosophila
      genome. In this study, I found that the Drosophila protein Ssp1/Mei-38 has
      significant homology to TPX2. Sequence conservation was limited to the putative
      spindle microtubule-associated region of TPX2, and intriguingly, D-TPX2 (Ssp1/Mei
      38) lacks Aurora A- and kinesin-5-binding domains, which are highly conserved in
      other animal and plant species, including many insects such as ants and bees. D
      TPX2 uniformly localised to kinetochore microtubule-enriched regions of the
      metaphase spindle in the S2 cell line, and it had microtubule binding and
      bundling activities in vitro. In comparison with other systems, the contribution
      of D-TPX2 to cell division seems to be minor; live cell imaging of microtubules
      and chromosomes after RNAi knockdown identified significant delay in chromosome
      congression in only 18% of the cells. Thus, while this conserved spindle protein
      is present in Drosophila, other mechanisms may largely compensate for its spindle
      assembly and chromosome segregation functions.

PMID- 22140520
TI  - TRAF6 and IRF7 control HIV replication in macrophages.
AB  - The innate immune system recognizes virus infection and evokes antiviral
      responses which include producing type I interferons (IFNs). The induction of IFN
      provides a crucial mechanism of antiviral defense by upregulating interferon
      stimulated genes (ISGs) that restrict viral replication. ISGs inhibit the
      replication of many viruses by acting at different steps of their viral cycle.
      Specifically, IFN treatment prior to in vitro human immunodeficiency virus (HIV)
      infection stops or significantly delays HIV-1 production indicating that potent
      inhibitory factors are generated. We report that HIV-1 infection of primary human
      macrophages decreases tumor necrosis factor receptor-associated factor 6 (TRAF6)
      and virus-induced signaling adaptor (VISA) expression, which are both components
      of the IFN signaling pathway controlling viral replication. Knocking down the
      expression of TRAF6 in macrophages increased HIV-1 replication and augmented the
      expression of IRF7 but not IRF3. Suppressing VISA had no impact on viral
      replication. Overexpression of IRF7 resulted in enhanced viral replication while
      knocking down IRF7 expression in macrophages significantly reduced viral output.
      These findings are the first demonstration that TRAF6 can regulate HIV-1
      production and furthermore that expression of IRF7 promotes HIV-1 replication.

PMID- 22140521
TI  - Serologic markers in relation to parasite exposure history help to estimate
      transmission dynamics of Plasmodium vivax.
AB  - Plasmodium vivax infection has been gaining attention because of its re-emergence
      in several parts of the world. Southeastern Turkey is one of the places in which
      persistent focal malaria caused exclusively by P. vivax parasites occurs.
      Although control and elimination studies have been underway for many years, no
      detailed study has been conducted to understand the mechanisms underlying the
      ineffective control of malaria in this region. Here, for the first time, using
      serologic markers we try to extract as much information as possible in this
      region to get a glimpse of P. vivax transmission. We conducted a sero
      immunological study, evaluating antibody responses of individuals living in
      Sanliurfa to four different P. vivax antigens; three blood-stage antigens
      (PvMSP119, PvAMA1-ecto, and PvSERA4) and one pre-erythrocytic stage antigen
      (PvCSP). The results suggest that a prior history of malaria infection and age
      can be determining factors for the levels and sustainability of naturally
      acquired antibodies. Significantly higher antibody responses to all the studied
      antigens were observed in blood smear-negative individuals with a prior history
      of malaria infection. Moreover, these individuals were significantly older than
      blood smear-negative individuals with no prior history of infection. These data
      from an area of sole P. vivax-endemic region may have important implications for
      the global malaria control/elimination programs and vaccine design.

PMID- 22140522
TI  - Home labour induction with retrievable prostaglandin pessary and continuous
      telemetric trans-abdominal fetal ECG monitoring.
AB  - OBJECTIVE: To evaluate the feasibility of continuous telemetric trans-abdominal
      fetal electrocardiogram (a-fECG) in women undergoing labour induction at home.
      STUDY DESIGN: Low risk women with singleton term pregnancy undergoing labour
      induction with retrievable, slow-release dinoprostone pessaries (n = 70) were
      allowed home for up to 24 hours, while a-fECG and uterine activity were monitored
      in hospital via wireless technology. Semi-structured diaries were analysed using
      a combined descriptive and interpretive approach. RESULTS: 62/70 women (89%) had
      successful home monitoring; 8 women (11%) were recalled because of signal loss.
      Home monitoring lasted between 2-22 hours (median 10 hours). Good quality signal
      was achieved most of the time (86%, SD 10%). 3 women were recalled back to
      hospital for suspicious a-fECG. In 2 cases suspicious a-fECG persisted, requiring
      Caesarean section after recall to hospital. 48/51 women who returned the diary
      coped well (94%); 46/51 were satisfied with home monitoring (90%). CONCLUSIONS:
      Continuous telemetric trans-abdominal fetal ECG monitoring of ambulatory women
      undergoing labour induction is feasible and acceptable to women.

PMID- 22140523
TI  - Type I interferon reaction to viral infection in interferon-competent,
      immortalized cell lines from the African fruit bat Eidolon helvum.
AB  - Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg,
      and henipaviruses, without overt clinical symptoms in the animals. It has been
      suspected that bats might have evolved particularly effective mechanisms to
      suppress viral replication. Here, we investigated interferon (IFN) response, 
      induction, -secretion and -signaling in epithelial-like cells of the relevant and
      abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell
      lines were generated; their potential to induce and react on IFN was confirmed,
      and biological assays were adapted to application in bat cell cultures, enabling
      comparison of landmark IFN properties with that of common mammalian cell lines.
      E. helvum cells were fully capable of reacting to viral and artificial IFN
      stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN
      protein secretion, and evidence of efficient IFN stimulated gene induction. In an
      Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction
      but evaded the IFN response by translational rather than transcriptional shutoff,
      similar to other Alphavirus infections. These novel IFN-competent cell lines will
      allow comparative research on zoonotic, bat-borne viruses in order to model
      mechanisms of viral maintenance and emergence in bat reservoirs.

PMID- 22140524
TI  - Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT
      system and early postnatal lethality.
AB  - The serotonin (5-HT) system densely innervates many brain areas and is important
      for proper brain development. To specifically ablate the 5-HT system we generated
      mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5
      HT-specific serotonin reuptake transporter (SERT) promoter. The majority of
      mutant mice died within a few days after birth. Immunohistochemical analysis of
      brains of these mice showed that initially 5-HT neurons are formed and the cortex
      is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT
      neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections
      were present in the cortex. The 5-HT system of mice heterozygous for the floxed
      Munc18-1 allele was indistinguishable from control mice. These data show that
      deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT
      system and suggests that the 5-HT system is important for postnatal survival.

PMID- 22140525
TI  - Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of
      FAAH inhibition.
AB  - Evidence shows that the endocannabinoid system modulates the addictive properties
      of nicotine. In the present study, we hypothesized that spontaneous withdrawal
      resulting from removal of chronically implanted transdermal nicotine patches is
      regulated by the endocannabinoid system. A 7-day nicotine dependence procedure
      (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in
      Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34
      hours following removal of nicotine patches, respectively. Further behavioral
      manifestations including decrease in locomotor activity and increased weight gain
      also occurred during withdrawal. Expression of spontaneous nicotine withdrawal
      was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA)
      in several brain structures including the amygdala, the hippocampus, the
      hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn
      glycerol were not significantly altered. Pharmacological inhibition of fatty acid
      amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation
      of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety
      as assessed by the elevated plus maze test and the shock-probe defensive burying
      paradigm, but did not prevent the occurrence of somatic signs. Together, the
      results indicate that pharmacological strategies aimed at enhancing
      endocannabinoid signaling may offer therapeutic advantages to treat the negative
      affective state produced by nicotine withdrawal, which is critical for the
      maintenance of tobacco use.

PMID- 22140526
TI  - Detecting low frequent loss-of-function alleles in genome wide association
      studies with red hair color as example.
AB  - Multiple loss-of-function (LOF) alleles at the same gene may influence a
      phenotype not only in the homozygote state when alleles are considered
      individually, but also in the compound heterozygote (CH) state. Such LOF alleles
      typically have low frequencies and moderate to large effects. Detecting such
      variants is of interest to the genetics community, and relevant statistical
      methods for detecting and quantifying their effects are sorely needed. We present
      a collapsed double heterozygosity (CDH) test to detect the presence of multiple
      LOF alleles at a gene. When causal SNPs are available, which may be the case in
      next generation genome sequencing studies, this CDH test has overwhelmingly
      higher power than single SNP analysis. When causal SNPs are not directly
      available such as in current GWA settings, we show the CDH test has higher power
      than standard single SNP analysis if tagging SNPs are in linkage disequilibrium
      with the underlying causal SNPs to at least a moderate degree (r2>0.1). The test
      is implemented for genome-wide analysis in the publically available software
      package GenABEL which is based on a sliding window approach. We provide the proof
      of principle by conducting a genome-wide CDH analysis of red hair color, a trait
      known to be influenced by multiple loss-of-function alleles, in a total of 7,732
      Dutch individuals with hair color ascertained. The association signals at the
      MC1R gene locus from CDH were uniformly more significant than traditional GWA
      analyses (the most significant P for CDH = 3.11*10-142 vs. P for rs258322 =
      1.33*10-66). The CDH test will contribute towards finding rare LOF variants in
      GWAS and sequencing studies.

PMID- 22140527
TI  - The multi-level action of fatty acids on adiponectin production by fat cells.
AB  - Current epidemics of diabetes mellitus is largely caused by wide spread obesity.
      The best-established connection between obesity and insulin resistance is the
      elevated and/or dysregulated levels of circulating free fatty acids that cause
      and aggravate insulin resistance, type 2 diabetes, cardiovascular disease and
      other hazardous metabolic conditions. Here, we investigated the effect of a major
      dietary saturated fatty acid, palmitate, on the insulin-sensitizing adipokine
      adiponectin produced by cultured adipocytes. We have found that palmitate rapidly
      inhibits transcription of the adiponectin gene and the release of adiponectin
      from adipocytes. Adiponectin gene expression is controlled primarily by PPARgamma
      and C/EBPalpha. Using mouse embryonic fibroblasts from C/EBPalpha-null mice, we
      have determined that the latter transcription factor may not solely mediate the
      inhibitory effect of palmitate on adiponectin transcription leaving PPARgamma as
      a likely target of palmitate. In agreement with this model, palmitate increases
      phosphorylation of PPARgamma on Ser273, and substitution of PPARgamma for the
      unphosphorylated mutant Ser273Ala blocks the effect of palmitate on adiponectin
      transcription. The inhibitory effect of palmitate on adiponectin gene expression
      requires its intracellular metabolism via the acyl-CoA synthetase 1-mediated
      pathway. In addition, we found that palmitate stimulates degradation of
      intracellular adiponectin by lysosomes, and the lysosomal inhibitor, chloroquine,
      suppressed the effect of palmitate on adiponectin release from adipocytes. We
      present evidence suggesting that the intracellular sorting receptor, sortilin,
      plays an important role in targeting of adiponectin to lysosomes. Thus, palmitate
      not only decreases adiponectin expression at the level of transcription but may
      also stimulate lysosomal degradation of newly synthesized adiponectin.

PMID- 22140528
TI  - Diverse roles of Eph/ephrin signaling in the mouse lens.
AB  - Recent genetic studies show that the Eph/ephrin bidirectional signaling pathway
      is associated with both congenital and age-related cataracts in mice and humans.
      We have investigated the molecular mechanisms of cataractogenesis and the roles
      of ephrin-A5 and EphA2 in the lens. Ephrin-A5 knockout -/- mice often display
      anterior polar cataracts while EphA2-/- lenses show very mild cortical or nuclear
      cataracts at weaning age. The anterior polar cataract of ephrin-A5-/- lenses is
      correlated with multilayers of aberrant cells that express alpha smooth muscle
      actin, a marker for mesenchymal cells. Only select fiber cells are altered in
      ephrin-A5-/- lenses. Moreover, the disruption of membrane-associated beta-catenin
      and E-cadherin junctions is observed in ephrin-A5-/- lens central epithelial
      cells. In contrast, EphA2-/- lenses display normal monolayer epithelium while
      disorganization is apparent in all lens fiber cells. Immunostaining of ephrin-A5
      proteins, highly expressed in lens epithelial cells, were not colocalized with
      EphA2 proteins, mainly expressed in lens fiber cells. Besides the previously
      reported function of ephrin-A5 in lens fiber cells, this work suggests that
      ephrin-A5 regulates beta-catenin signaling and E-cadherin to prevent lens
      anterior epithelial cells from undergoing the epithelial-to-mesenchymal
      transition while EphA2 is essential for controlling the organization of lens
      fiber cells through an unknown mechanism. Ephrin-A5 and EphA2 likely interacting
      with other members of Eph/ephrin family to play diverse functions in lens
      epithelial cells and/or fiber cells.

PMID- 22140529
TI  - An earthworm riddle: systematics and phylogeography of the Spanish lumbricid
      Postandrilus.
AB  - BACKGROUND: As currently defined, the genus Postandrilus Qui and Bouche, 1998,
      (Lumbricidae) includes six earthworm species, five occurring in Majorca (Baleares
      Islands, western Mediterranean) and another in Galicia (NW Spain). This disjunct
      and restricted distribution raises some interesting phylogeographic questions:
      (1) Is Postandrilus distribution the result of the separation of the Baleares
      Kabylies (BK) microplate from the proto-Iberian Peninsula in the Late Oligocene
      (30-28 Mya)--vicariant hypothesis? (2) Did Postandrilus diversify in Spain and
      then colonize the Baleares during the Messinian salinity crisis (MSC) 5.96-5.33
      Mya--dispersal hypothesis? (3) Is the distribution the result of a two-step
      process--vicariance with subsequent dispersal? METHODOLOGY/PRINCIPAL FINDINGS: To
      answer these questions and assess Postandrilus evolutionary relationships and
      systematics, we collected all of the six Postandrilus species (46 specimens - 16
      locations) and used Aporrectodea morenoe and three Prosellodrilus and two
      Cataladrilus species as the outgroup. Regions of the nuclear 28S rDNA and
      mitochondrial 16S rDNA, 12S rDNA, ND1, COII and tRNA genes (4,666 bp) were
      sequenced and analyzed using maximum likelihood and Bayesian methods of
      phylogenetic and divergence time estimation. The resulting trees revealed six new
      Postandrilus species in Majorca that clustered with the other five species
      already described. This Majorcan clade was sister to an Iberian clade including
      A. morenoe (outgroup) and Postandrilus bertae. Our phylogeny and divergence time
      estimates indicated that the split between the Iberian and Majorcan Postandrilus
      clades took place 30.1 Mya, in concordance with the break of the BK microplate
      from the proto-Iberian Peninsula, and that the present Majorcan clade diversified
      5.7 Mya, during the MSC. CONCLUSIONS: Postandrilus is highly diverse including
      multiple cryptic species in Majorca. The genus is not monophyletic and invalid as
      currently defined. Postandrilus is of vicariant origin and its radiation began in
      the Late Oligocene.

PMID- 22140530
TI  - Atmospheric-pressure plasma jet induces apoptosis involving mitochondria via
      generation of free radicals.
AB  - The plasma jet has been proposed as a novel therapeutic method for anticancer
      treatment. However, its biological effects and mechanism of action remain
      elusive. Here, we investigated its cell death effects and underlying molecular
      mechanisms, using air and N2 plasma jets from a micro nozzle array. Treatment
      with air or N2 plasma jets caused apoptotic death in human cervical cancer HeLa
      cells, simultaneously with depolarization of mitochondrial membrane potential. In
      addition, the plasma jets were able to generate reactive oxygen species (ROS),
      which function as surrogate apoptotic signals by targeting the mitochondrial
      membrane potential. Antioxidants or caspase inhibitors ameliorated the apoptotic
      cell death induced by the air and N2 plasma jets, suggesting that the plasma jet
      may generate ROS as a proapoptotic cue, thus initiating mitochondria-mediated
      apoptosis. Taken together, our data suggest the potential employment of plasma
      jets as a novel therapy for cancer.

PMID- 22140531
TI  - A cluster-randomised trial of staff education to improve the quality of life of
      people with dementia living in residential care: the DIRECT study.
AB  - BACKGROUND: The Dementia In Residential care: EduCation intervention Trial
      (DIRECT) was conducted to determine if delivery of education designed to meet the
      perceived need of GPs and care staff improves the quality of life of participants
      with dementia living in residential care. METHODOLOGY/PRINCIPAL FINDINGS: This
      cluster-randomised controlled trial was conducted in 39 residential aged care
      facilities in the metropolitan area of Perth, Western Australia. 351 care
      facility residents aged 65 years and older with Mini-Mental State Examination <=
      24, their GPs and facility staff participated. Flexible education designed to
      meet the perceived needs of learners was delivered to GPs and care facility staff
      in intervention groups. The primary outcome of the study was self-rated quality
      of life of participants with dementia, measured using the QOL-Alzheimer's Disease
      Scale (QOL-AD) at 4 weeks and 6 months after the conclusion of the intervention.
      Analysis accounted for the effect of clustering by using multi-level regression
      analysis. Education of GPs or care facility staff did not affect the primary
      outcome at either 4 weeks or 6 months. In a post hoc analysis excluding
      facilities in which fewer than 50% of staff attended an education session, self
      rated QOL-AD scores were 6.14 points (adjusted 95%CI 1.14, 11.15) higher at four
      week follow-up among residents in facilities randomly assigned to the education
      intervention. CONCLUSION: The education intervention directed at care facilities
      or GPs did not improve the quality of life ratings of participants with dementia
      as a group. This may be explained by the poor adherence to the intervention
      programme, as participants with dementia living in facilities where staff
      participated at least minimally seemed to benefit. TRIAL REGISTRATION:
      ANZCTR.org.au ACTRN12607000417482.

PMID- 22140532
TI  - ERG deregulation induces PIM1 over-expression and aneuploidy in prostate
      epithelial cells.
AB  - The ERG gene belongs to the ETS family of transcription factors and has been
      found to be involved in atypical chromosomal rearrangements in several cancers.
      To gain insight into the oncogenic activity of ERG, we compared the gene
      expression profile of NIH-3T3 cells stably expressing the coding regions of the
      three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG. We
      found that all three ERG fusions significantly up-regulate PIM1 expression in the
      NIH-3T3 cell line. PIM1 is a serine/threonine kinase frequently over-expressed in
      cancers of haematological and epithelial origin. We show here that tERG
      expression induces PIM1 in the non-malignant prostate cell line RWPE-1,
      strengthening the relation between tERG and PIM1 up-regulation in the initial
      stages of prostate carcinogenesis. Silencing of tERG reversed PIM1 induction. A
      significant association between ERG and PIM1 expression in clinical prostate
      carcinoma specimens was found, suggesting that such a mechanism may be relevant
      in vivo. Chromatin Immunoprecipitation experiments showed that tERG directly
      binds to PIM1 promoter in the RWPE-1 prostate cell line, suggesting that tERG
      could be a direct regulator of PIM1 expression. The up-regulation of PIM1 induced
      by tERG over-expression significantly modified Cyclin B1 levels and increased the
      percentage of aneuploid cells in the RWPE-1 cell line after taxane-based
      treatment. Here we provide the first evidence for an ERG-mediated PIM1 up
      regulation in prostate cells in vitro and in vivo, suggesting a direct effect of
      ERG transcriptional activity in the alteration of genetic stability.

PMID- 22140533
TI  - Elucidation of the dual role of Mycobacterial MoeZR in molybdenum cofactor
      biosynthesis and cysteine biosynthesis.
AB  - The pathway of molybdenum cofactor biosynthesis has been studied in detail by
      using proteins from Mycobacterium species, which contain several homologs
      associated with the first steps of Moco biosynthesis. While all Mycobacteria
      species contain a MoeZR, only some strains have acquired an additional homolog,
      MoeBR, by horizontal gene transfer. The role of MoeBR and MoeZR was studied in
      detail for the interaction with the two MoaD-homologs involved in Moco
      biosynthesis, MoaD1 and MoaD2, in addition to the CysO protein involved in
      cysteine biosynthesis. We show that both proteins have a role in Moco
      biosynthesis, while only MoeZR, but not MoeBR, has an additional role in cysteine
      biosynthesis. MoeZR and MoeBR were able to complement an E. coli moeB mutant
      strain, but only in conjunction with the Mycobacterial MoaD1 or MoaD2 proteins.
      Both proteins were able to sulfurate MoaD1 and MoaD2 in vivo, while only MoeZR
      additionally transferred the sulfur to CysO. Our in vivo studies show that
      Mycobacteria have acquired several homologs to maintain Moco biosynthesis. MoeZR
      has a dual role in Moco- and cysteine biosynthesis and is involved in the
      sulfuration of MoaD and CysO, whereas MoeBR only has a role in Moco biosynthesis,
      which is not an essential function for Mycobacteria.

PMID- 22140534
TI  - Dual function of histone H3 lysine 36 methyltransferase ASH1 in regulation of Hox
      gene expression.
AB  - Hox genes play important roles in haematopoietic development in mammals. ASH1 is
      a member of the trithorax group (trxG) that is required for proper expression of
      Hox genes and is preferentially expressed in haematopoietic stem cells. We have
      recently reported that ASH1 methylates histone H3 at lysine 36 (K36) but its
      biological function has remained elusive. Here we show that ASH1 regulates Hox
      gene expression positively and negatively in a leukemic cell line K562 and is
      required for myelomonocytic differentiation of murine haematopoietic stem cells.
      ASH1 binds to endogenous Hox loci in K562 cells and its knockdown causes reduced
      expression of Hox genes. In addition, ASH1 and MLL1 induce more than 100-fold
      activation of Hox promoters in HeLa cells if expressed simultaneously but not
      individually. Notably, ASH1 harbouring a point mutation that kills
      methyltransferase activity is more efficient than wild type ASH1 in Hox gene
      activation, indicating that K36 methylation is not a prerequisite for Hox gene
      expression. Moreover, tethering wild type or catalytically inactive
      methyltransferase domain of ASH1 to a heterologous promoter causes downregulation
      or upregulation, respectively, of transcription, supporting a hypothesis that K36
      methylation imparts repression. Knockdown of ASH1 in K562 cells in vitro causes
      increased expression of epsilon-globin gene and reduced expression of
      myelomonocytic markers GPIIb and GPIIIa, whereas knockdown of ASH1 in murine
      haematopoietic stem cells in vivo results in decreased number of macrophages and
      granulocytes, a phenotype similar to that induced by loss of mll1 function. Taken
      together, our data suggest that ASH1 and MLL1 synergize in activation of Hox
      genes and thereby regulate development of myelomonocytic lineages from
      haematopoietic stem cells.

PMID- 22140535
TI  - Dynamics of regulatory T-cells during pregnancy: effect of HIV infection and
      correlations with other immune parameters.
AB  - OBJECTIVES: Regulatory T cells (Treg) increase in the context of HIV infection
      and pregnancy. We studied Treg subpopulations in HIV-infected and uninfected
      women during pregnancy and their relationship with inflammation, activation and
      cell-mediated immunity (CMI). DESIGN AND METHODS: Blood obtained from 20 HIV
      infected and 18 uninfected women during early and late gestation was used to
      measure Treg and activated T cells (Tact) by flow cytometry; plasma cytokines and
      inflammatory markers by ELISA and chemoluminescence; and CMI against varicella
      zoster virus (VZV) by lymphocyte proliferation. RESULTS AND CONCLUSIONS: Compared
      with uninfected women, HIV-infected participants had higher frequencies of Treg
      subpopulations in early pregnancy, including CD4+CD25+FoxP3+%, CD8+CD25+FoxP3+%,
      CD4+TGFbeta+% and CD4+IL10+%. In contrast, Treg frequencies were lower during
      late pregnancy in HIV-infected compared with uninfected women, including
      CD8+TGFbeta+%, CD4+CTLA4+% and CD8+CTLA4+%. VZV-CMI, which was lower in HIV
      infected compared with uninfected pregnant women, was inversely correlated with
      CD4+FoxP3+%, CD8+FoxP3+% and CD8+TGFbeta+% in HIV-infected, but not in uninfected
      pregnant women. beta2-microglobulin, neopterin, IL1, IL4, IL8, IL10, IFNgamma and
      TNFalpha plasma concentrations as well as Tact were higher in HIV-infected
      compared with uninfected women throughout pregnancy. In HIV-infected, but not in
      uninfected women, inflammatory, Th1, Th2 and regulatory cytokines increased with
      higher Treg%, suggesting that inflammation and regulation have a common
      pathophysiologic origin in the context of HIV infection. In HIV-infected and more
      commonly in uninfected pregnant women, higher Treg% correlated with lower Tact%.
      We conclude that Treg have different dynamics during pregnancy in HIV-infected
      and uninfected women. Higher levels of inflammatory cytokines and lower Treg%
      during late pregnancy in HIV-infected women may contribute to their increased
      incidence of maternal-fetal morbidity.

PMID- 22140536
TI  - Tamiflu-resistant but HA-mediated cell-to-cell transmission through apical
      membranes of cell-associated influenza viruses.
AB  - The infection of viruses to a neighboring cell is considered to be beneficial in
      terms of evasion from host anti-virus defense systems. There are two pathways for
      viral infection to "right next door": one is the virus transmission through cell
      cell fusion by forming syncytium without production of progeny virions, and the
      other is mediated by virions without virus diffusion, generally designated cell
      to-cell transmission. Influenza viruses are believed to be transmitted as cell
      free virus from infected cells to uninfected cells. Here, we demonstrated that
      influenza virus can utilize cell-to-cell transmission pathway through apical
      membranes, by handover of virions on the surface of an infected cell to adjacent
      host cells. Live cell imaging techniques showed that a recombinant influenza
      virus, in which the neuraminidase gene was replaced with the green fluorescence
      protein gene, spreads from an infected cell to adjacent cells forming infected
      cell clusters. This type of virus spreading requires HA activation by protease
      treatment. The cell-to-cell transmission was also blocked by amantadine, which
      inhibits the acidification of endosomes required for uncoating of influenza virus
      particles in endosomes, indicating that functional hemagglutinin and endosome
      acidification by M2 ion channel were essential for the cell-to-cell influenza
      virus transmission. Furthermore, in the cell-to-cell transmission of influenza
      virus, progeny virions could remain associated with the surface of infected cell
      even after budding, for the progeny virions to be passed on to adjacent
      uninfected cells. The evidence that cell-to-cell transmission occurs in influenza
      virus lead to the caution that local infection proceeds even when treated with
      neuraminidase inhibitors.

PMID- 22140537
TI  - Increased expression of PS1 is sufficient to elevate the level and activity of
      gamma-secretase in vivo.
AB  - Increase in the generation and deposition of amyloid-beta (Abeta) plays a central
      role in the development of Alzheimer's Disease (AD). Elevation of the activity of
      gamma-secretase, a key enzyme required for the generation for Abeta, can thus be
      a potential risk factor in AD. However, it is not known whether gamma-secretase
      can be upregulated in vivo. While in vitro studies showed that expression of all
      four components of gamma-secretase (Nicastrin, Presenilin, Pen-2 and Aph-1) are
      required for upregulation of gamma-secretase, it remains to be established as to
      whether this is true in vivo. To investigate whether overexpressing a single
      component of the gamma-secretase complex is sufficient to elevate its level and
      activity in the brain, we analyzed transgenic mice expressing either wild type or
      familial AD (fAD) associated mutant PS1. In contrast to cell culture studies,
      overexpression of either wild type or mutant PS1 is sufficient to increase levels
      of Nicastrin and Pen-2, and elevate the level of active gamma-secretase complex,
      enzymatic activity of gamma-secretase and the deposition of Abeta in brains of
      mice. Importantly, gamma-secretase comprised of mutant PS1 is less active than
      that of wild type PS1-containing gamma-secretase; however, gamma-secretase
      comprised of mutant PS1 cleaves at the Abeta42 site of APP-CTFs more efficiently
      than at the Abeta40 site, resulting in greater accumulation of Abeta deposits in
      the brain. Our data suggest that whereas fAD-linked PS1 mutants cause early onset
      disease, upregulation of PS1/gamma-secretase activity may be a risk factor for
      late onset sporadic AD.

PMID- 22140538
TI  - Longitudinal study of the dynamics of vaginal microflora during two consecutive
      menstrual cycles.
AB  - BACKGROUND: Although the vaginal microflora (VMF) has been well studied,
      information on the fluctuation of the different bacterial species throughout the
      menstrual cycle and the information on events preceding the presence of disturbed
      VMF is still very limited. Documenting the dynamics of the VMF during the
      menstrual cycle might provide better insights. In this study, we assessed the
      presence of different Lactobacillus species in relation to the BV associated
      species during the menstrual cycle, assessed the influence of the menstrual cycle
      on the different categories of vaginal microflora and assessed possible causes,
      such as menstruation and sexual intercourse, of VMF disturbance. To our
      knowledge, this is the first longitudinal study in which swabs and Gram stains
      were available for each day of two consecutive menstrual cycles, whereby 8 grades
      of VMF were distinguished by Gram stain analysis, and whereby the swabs were
      cultured every 7(th) day and identification of the bacterial isolates was carried
      out with a molecular technique. METHODS: Self-collected vaginal swabs were
      obtained daily from 17 non pregnant, menarchal volunteers, and used for daily
      Gram staining and weekly culture. Bacterial isolates were identified with tDNA
      PCR and 16 S rRNA gene sequencing. RESULTS: Nine women presented with
      predominantly normal VMF and the 8 others had predominantly disturbed VMF. The
      overall VMF of each volunteer was characteristic and rather stable. Menses and
      antimicrobials were the major disturbing factors of the VMF. Disturbances were
      always accompanied by a rise in Gram positive cocci, which also appeared to be a
      significant group within the VMF in general. CONCLUSIONS: We observed a huge
      interindividual variability of predominantly stable VMF types. The importance of
      Gram positive cocci in VMF is underestimated. L. crispatus was the species that
      was most negatively affected by the menses, whereas the presence of the other
      lactobacilli was less variable.

PMID- 22140539
TI  - Fibronectin protects from excessive liver fibrosis by modulating the availability
      of and responsiveness of stellate cells to active TGF-beta.
AB  - Fibrotic tissue in the liver is mainly composed of collagen. Fibronectin, which
      is also present in fibrotic matrices, is required for collagen matrix assembly in
      vitro. It also modulates the amount of growth factors and their release from the
      matrix. We therefore examined the effects of the absence of fibronectin on the
      development of fibrosis in mice.Conditional deletion of fibronectin in the liver
      using the Mx promoter to drive cre expression resulted in increased collagen
      production and hence a more pronounced fibrosis in response to
      dimethylnitrosamine in mice. Exclusive deletion of fibronectin in hepatocytes or
      normalization of circulating fibronectin in Mx-cKO mice did not affect the
      development of fibrosis suggesting a role for fibronectin production by other
      liver cell types. The boosted fibrosis in fibronectin-deficient mice was
      associated with enhanced stellate cell activation and proliferation, elevated
      concentrations of active TGF-beta, and increased TGF-beta-mediated signaling.In
      vitro experiments revealed that collagen-type-I production by fibronectin
      deficient hepatic stellate cells stimulated with TGF-beta was more pronounced,
      and was associated with augmented Smad3-mediated signaling. Interfering with TGF
      beta signaling using SB431542 normalized collagen-type-I production in
      fibronectin-deficient hepatic stellate cells. Furthermore, precoating culture
      plates with fibronectin, but not collagen, or providing fibronectin fibrils
      unable to interact with RGD binding integrins via the RGD domain significantly
      diminished the amount of active TGF-beta in fibronectin-deficient stellate cells
      and normalized collagen-type-I production in response to TGF-beta stimulation.
      Thus, excessive stellate cell activation and production of collagen results from
      increased active TGF-beta and TGF-beta signaling in the absence of fibronectin.In
      conclusion, our data indicate that fibronectin controls the availability of
      active TGF-beta in the injured liver, which impacts the severity of the resulting
      fibrosis. We therefore propose a novel role for locally produced fibronectin in
      protecting the liver from an excessive TGF-beta-mediated response.

PMID- 22140540
TI  - FADS2 function loss at the cancer hotspot 11q13 locus diverts lipid signaling
      precursor synthesis to unusual eicosanoid fatty acids.
AB  - BACKGROUND: Genes coding for the fatty acid desaturases (FADS1, 2, 3) localized
      at the cancer genomic hotspot 11q13 locus are required for the biosynthesis of 20
      carbon polyunsaturated fatty acids (PUFA) that are direct eicosanoid precursors.
      In several cancer cell lines, FADS2 encoded Delta6 and Delta8 desaturation is not
      functional. METHODOLOGY/PRINCIPAL FINDINGS: Analyzing MCF7 cell fatty acids with
      detailed structural mass spectrometry, we show that in the absence of FADS2
      activity, the FADS1 product Delta5-desaturase operates to produce 5,11,14-20?3
      and 5,11,14,17-20?4. These PUFA are missing the 8-9 double bond of the eicosanoid
      signaling precursors arachidonic acid (5,8,11,14-20?4) and eicosapentaenoic acid
      (5,8,11,14,17-20?5). Heterologous expression of FADS2 restores Delta6 and Delta8
      desaturase activity and normal eicosanoid precursor synthesis.
      CONCLUSIONS/SIGNIFICANCE: The loss of FADS2-encoded activities in cancer cells
      shuts down normal PUFA biosynthesis, deleting the endogenous supply of eicosanoid
      and downstream docosanoid precursors, and replacing them with unusual butylene
      interrupted fatty acids. If recapitulated in vivo, the normal eicosanoid and
      docosanoid cell signaling milieu would be depleted and altered due to reduction
      and substitution of normal substrates with unusual substrates, with unpredictable
      consequences for cellular communication.

PMID- 22140541
TI  - Rapid amygdala gamma oscillations in response to eye gaze.
AB  - BACKGROUND: The eye gaze of other individuals conveys important social
      information and can trigger multiple psychological activities; some of which,
      such as emotional reactions and attention orienting, occur very rapidly. Although
      some neuroscientific evidence has suggested that the amygdala may be involved in
      such rapid gaze processing, no evidence has been reported concerning the speed at
      which the amygdala responds to eye gaze. METHODOLOGY/PRINCIPAL FINDINGS: To
      investigate this issue, we recorded electrical activity within the amygdala of
      six subjects using intracranial electrodes. Subjects observed images of eyes and
      mosaics pointing in averted and straight directions. The amygdala showed higher
      gamma-band oscillations for eye gaze than for mosaics, which peaked at 200 ms
      regardless of the direction of the gaze. CONCLUSION: These results indicate that
      the human amygdala rapidly processes eye gaze.

PMID- 22140542
TI  - Clonal replacement of epidemic methicillin-resistant Staphylococcus aureus
      strains in a German university hospital over a period of eleven years.
AB  - Worldwide, methicillin-resistant Staphylococcus aureus (MRSA) pose an increased
      risk for healthcare- and community-associated infections. Since the first report
      of MRSA in England in 1961, several distinct clones or strains have emerged.
      Changes within the MRSA population of whole countries, small regions or of single
      hospitals have been observed with some clones replacing others. In this study,
      the clonal replacement of MRSA isolates in a South-eastern German tertiary care
      hospital between 2000 and 2010 is described based on microarray analyses of 778
      isolates and at least 50 MRSA per year. Within these eleven years, four common
      epidemic strains, CC22-MRSA-IV, CC45-MRSA-IV, CC5/ST228-MRSA-I (including a
      variant with a truncated SCCmec element) and CC5-MRSA-II were identified. The PVL
      negative CC22-MRSA-IV strain (Barnim Epidemic Strain, UK-EMRSA-15) was detected
      for the first time in 2001 and its abundance increased since then to 58.6% in
      2010. CC5-MRSA-II increased from 2% (2000) to about 30% (2003), and since then it
      fluctuates between 23 and 37% of isolates. CC5/ST228-MRSA-I decreased from about
      the half of tested isolates (2000) to 2.3% (2010). A similar trend was observed
      for CC45-MRSA-IV, which decreased drastically down to 3.4% in 2010 after reaching
      a maximum of 62.0% in 2002. Seventeen other PVL-negative MRSA strains were
      identified sporadically with no significant trend being observed. Seven PVL
      positive MRSA strains were found, but they remained rare during the study period
      accounting together for 2.7% of isolates.

PMID- 22140543
TI  - Coerced hospital admission and symptom change--a prospective observational multi
      centre study.
AB  - INTRODUCTION: Coerced admission to psychiatric hospitals, defined by legal status
      or patient's subjective experience, is common. Evidence on clinical outcomes
      however is limited. This study aimed to assess symptom change over a three month
      period following coerced admission and identify patient characteristics
      associated with outcomes. METHOD: At study sites in 11 European countries
      consecutive legally involuntary patients and patients with a legally voluntary
      admission who however felt coerced, were recruited and assessed by independent
      researchers within the first week after admission. Symptoms were assessed on the
      Brief Psychiatric Rating Scale. Patients were re-assessed after one and three
      months. RESULTS: The total sample consisted of 2326 legally coerced patients and
      764 patients with a legally voluntary admission who felt coerced. Symptom levels
      significantly improved over time. In a multivariable analysis, higher baseline
      symptoms, being unemployed, living alone, repeated hospitalisation, being legally
      a voluntary patient but feeling coerced, and being initially less satisfied with
      treatment were all associated with less symptom improvement after one month and,
      other than initial treatment satisfaction, also after three months. The
      diagnostic group was not linked with outcomes. DISCUSSION: On average patients
      show significant but limited symptom improvements after coerced hospital
      admission, possibly reflecting the severity of the underlying illnesses. Social
      factors, but not the psychiatric diagnosis, appear important predictors of
      outcomes. Legally voluntary patients who feel coerced may have a poorer prognosis
      than legally involuntary patients and deserve attention in research and clinical
      practice.

PMID- 22140544
TI  - Doubly uniparental inheritance of mitochondria as a model system for studying
      germ line formation.
AB  - BACKGROUND: Doubly Uniparental Inheritance (DUI) of mitochondria occurs when both
      mothers and fathers are capable of transmitting mitochondria to their offspring,
      in contrast to the typical Strictly Maternal Inheritance (SMI). DUI was found in
      some bivalve molluscs, in which two mitochondrial genomes are inherited, one
      through eggs, the other through sperm. During male embryo development,
      spermatozoon mitochondria aggregate in proximity of the first cleavage furrow and
      end up in the primordial germ cells, while they are dispersed in female embryos.
      METHODOLOGY/PRINCIPAL FINDINGS: We used MitoTracker, microtubule staining and
      transmission electron microscopy to examine the mechanisms of this unusual
      distribution of sperm mitochondria in the DUI species Ruditapes philippinarum.
      Our results suggest that in male embryos the midbody deriving from the mitotic
      spindle of the first division concurs in positioning the aggregate of sperm
      mitochondria. Furthermore, an immunocytochemical analysis showed that the germ
      line determinant Vasa segregates close to the first cleavage furrow.
      CONCLUSIONS/SIGNIFICANCE: In DUI male embryos, spermatozoon mitochondria
      aggregate in a stable area on the animal-vegetal axis: in organisms with spiral
      segmentation this zone is not involved in cleavage, so the aggregation is
      maintained. Moreover, sperm mitochondria reach the same embryonic area in which
      also germ plasm is transferred. In 2-blastomere embryos, the segregation of sperm
      mitochondria in the same region with Vasa suggests their contribution in male
      germ line formation. In DUI male embryos, M-type mitochondria must be recognized
      by egg factors to be actively transferred in the germ line, where they become
      dominant replacing the Balbiani body mitochondria. The typical features of germ
      line assembly point to a common biological mechanism shared by DUI and SMI
      organisms. Although the molecular dynamics of the segregation of sperm
      mitochondria in DUI species are unknown, they could be a variation of the
      mechanism regulating the mitochondrial bottleneck in all metazoans.

PMID- 22140545
TI  - Convergent sets of data from in vivo and in vitro methods point to an active role
      of Hsp60 in chronic obstructive pulmonary disease pathogenesis.
AB  - BACKGROUND: It is increasingly clear that some heat shock proteins (Hsps) play a
      role in inflammation. Here, we report results showing participation of Hsp60 in
      the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated
      by data from both in vivo and in vitro analyses. METHODS AND RESULTS: Bronchial
      biopsies from patients with stable COPD, smoker controls with normal lung
      function, and non-smoker controls were studied. We quantified by
      immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF
      1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were
      increased during progression of disease. We found also a positive correlation
      between the number of neutrophils and Hsp60 levels. Double-immunostaining showed
      that Hsp60-positive neutrophils were significantly increased in COPD patients. We
      then investigated in vitro the effect on Hsp60 expression in bronchial epithelial
      cells (16HBE) caused by oxidative stress, a hallmark of COPD mucosa, which we
      induced with H2O2. This stressor determined increased levels of Hsp60 through a
      gene up-regulation mechanism involving NFkB-p65. Release of Hsp60 in the
      extracellular medium by the bronchial epithelial cells was also increased after
      H2O2 treatment in the absence of cell death. CONCLUSIONS: This is the first
      report clearly pointing to participation of Hsps, particularly Hsp60, in COPD
      pathogenesis. Hsp60 induction by NFkB-p65 and its release by epithelial cells
      after oxidative stress can have a role in maintaining inflammation, e.g., by
      stimulating neutrophils activity. The data open new scenarios that might help in
      designing efficacious anti-inflammatory therapies centered on Hsp60 and
      applicable to COPD.

PMID- 22140546
TI  - Spectrum of oncogenic driver mutations in lung adenocarcinomas from East Asian
      never smokers.
AB  - PURPOSE: We previously showed that 90% (47 of 52; 95% CI, 0.79 to 0.96) of lung
      adenocarcinomas from East Asian never-smokers harbored well-known oncogenic
      mutations in just four genes: EGFR, HER2, ALK, and KRAS. Here, we sought to
      extend these findings to more samples and identify driver alterations in tumors
      negative for these mutations. EXPERIMENTAL DESIGN: We have collected and analyzed
      202 resected lung adenocarcinomas from never smokers seen at Fudan University
      Shanghai Cancer Center. Since mutations were mutually exclusive in the first 52
      examined, we determined the status of EGFR, KRAS, HER2, ALK, and BRAF in stepwise
      fashion as previously described. Samples negative for mutations in these 5 genes
      were subsequently examined for known ROS1 fusions by RT-PCR and direct
      sequencing. RESULTS: 152 tumors (75.3%) harbored EGFR mutations, 12 (6%) had HER2
      mutations, 10 (5%) had ALK fusions all involving EML4 as the 5' partner, 4 (2%)
      had KRAS mutations, and 2 (1%) harbored ROS1 fusions. No BRAF mutation were
      detected. CONCLUSION: The vast majority (176 of 202; 87.1%, 95% CI: 0.82 to 0.91)
      of lung adenocarcinomas from never smokers harbor mutant kinases sensitive to
      available TKIs. Interestingly, patients with EGFR mutant patients tend to be
      older than those without EGFR mutations (58.3 Vs 54.3, P = 0.016) and patient
      without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs
      57.9, P = 0.013). Collectively, these data indicate that the majority of never
      smokers with lung adenocarcinoma could benefit from treatment with a specific
      tyrosine kinase inhibitor.

PMID- 22140547
TI  - The Golgi localization of GOLPH2 (GP73/GOLM1) is determined by the transmembrane
      and cytoplamic sequences.
AB  - Golgi phosphoprotein 2 (GOLPH2) is a resident Golgi type-II membrane protein
      upregulated in liver disease. Given that GOLPH2 traffics through endosomes and
      can be secreted into the circulation, it is a promising serum marker for liver
      diseases. The structure of GOLPH2 and the functions of its different protein
      domains are not known. In the current study, we investigated the structural
      determinants for Golgi localization using a panel of GOLPH2 truncation mutants.
      The Golgi localization of GOLPH2 was not affected by the deletion of the C
      terminal part of the protein. A truncated mutant containing the N-terminal
      portion (the cytoplasmic tail and transmembrane domain (TMD)) localized to the
      Golgi. Sequential deletion analysis of the N-terminal indicated that the TMD with
      a positively charged residue in the cytoplasmic N-terminal tail were sufficient
      to support Golgi localization. We also showed that both endogenous and secreted
      GOLPH2 exist as a disulfide-bonded dimer, and the coiled-coil domain was
      sufficient for dimerization. This structural knowledge is important for the
      understanding the pathogenic role of GOLPH2 in liver diseases, and the
      development of GOLPH2-based hepatocellular cancer diagnostic methods.

PMID- 22140549
TI  - Minimising mortality in endangered raptors due to power lines: the importance of
      spatial aggregation to optimize the application of mitigation measures.
AB  - Electrocution by power lines is one of the main causes of non-natural mortality
      in birds of prey. In an area in central Spain, we surveyed 6304 pylons from 333
      power lines to determine electrocution rates, environmental and design factors
      that may influence electrocution and the efficacy of mitigation measures used to
      minimise electrocution cases. A total of 952 electrocuted raptors, representing
      14 different species, were observed. Electrocuted raptors were concentrated in
      certain areas and the environmental factors associated with increased
      electrocution events were: greater numbers of prey animals; greater vegetation
      cover; and shorter distance to roads. The structural elements associated with
      electrocutions were shorter strings of insulators, one or more phases over the
      crossarm, cross-shaped design and pylon function. Of the 952 carcasses found, 148
      were eagles, including golden eagle (Aquila chrysaetos), Spanish imperial eagle
      (Aquila adalberti) and Bonelli's eagle (Aquila fasciata). Electrocuted eagles
      were clustered in smaller areas than other electrocuted raptors. The factors
      associated with increased eagle electrocution events were: pylons function,
      shorter strings of insulators, higher slopes surrounding the pylon, and more
      numerous potential prey animals. Pylons with increased string of insulators had
      lower raptor electrocution rates than unimproved pylons, although this technique
      was unsuccessful for eagles. Pylons with cable insulation showed higher
      electrocution rates than unimproved pylons, both for raptors and eagles, despite
      this is the most widely used and recommended mitigation measure in several
      countries. To optimize the application of mitigation measures, our results
      recommend the substitution of pin-type insulators to suspended ones and
      elongating the strings of insulators.

PMID- 22140548
TI  - Heterozygous yeast deletion collection screens reveal essential targets of Hsp90.
AB  - Hsp90 is an essential eukaryotic chaperone with a role in folding specific
      "client" proteins such as kinases and hormone receptors. Previously performed
      homozygous diploid yeast deletion collection screens uncovered broad requirements
      for Hsp90 in cellular transport and cell cycle progression. These screens also
      revealed that the requisite cellular functions of Hsp90 change with growth
      temperature. We present here for the first time the results of heterozygous
      deletion collection screens conducted at the hypothermic stress temperature of 15
      degrees C. Extensive bioinformatic analyses were performed on the resulting data
      in combination with data from homozygous and heterozygous screens previously
      conducted at normal (30 degrees C) and hyperthermic stress (37 degrees C) growth
      temperatures. Our resulting meta-analysis uncovered extensive connections between
      Hsp90 and (1) general transcription, (2) ribosome biogenesis and (3) GTP binding
      proteins. Predictions from bioinformatic analyses were tested experimentally,
      supporting a role for Hsp90 in ribosome stability. Importantly, the integrated
      analysis of the 15 degrees C heterozygous deletion pool screen with previously
      conducted 30 degrees C and 37 degrees C screens allows for essential genetic
      targets of Hsp90 to emerge. Altogether, these novel contributions enable a more
      complete picture of essential Hsp90 functions.

PMID- 22140550
TI  - gamma-Radiation promotes immunological recognition of cancer cells through
      increased expression of cancer-testis antigens in vitro and in vivo.
AB  - BACKGROUND: gamma-radiation is an effective treatment for cancer. There is
      evidence that radiotherapy supports tumor-specific immunity. It was described
      that irradiation induces de novo protein synthesis and enhances antigen
      presentation, we therefore investigated whether gamma-radiation results in
      increased expression of cancer-testis (CT) antigens and MHC-I, thus allowing
      efficient immunological control. This is relevant because the expression of CT
      antigens and MHC-I on tumor cells is often heterogeneous. We found that the
      changes induced by gamma-radiation promote the immunological recognition of the
      tumor, which is illustrated by the increased infiltration by lymphocytes after
      radiotherapy. METHODS/FINDINGS: We compared the expression of CT-antigens and MHC
      I in various cancer cell lines and fresh biopsies before and after in vitro
      irradiation (20 Gy). Furthermore, we compared paired biopsies that were taken
      before and after radiotherapy from sarcoma patients. To investigate whether the
      changed expression of CT-antigens and MHC-I is specific for gamma-radiation or is
      part of a generalized stress response, we analyzed the effect of hypoxia,
      hyperthermia and genotoxic stress on the expression of CT-antigens and MHC-I. In
      vitro irradiation of cancer cell lines and of fresh tumor biopsies induced a
      higher or de novo expression of different CT-antigens and a higher expression of
      MHC-I in a time- and dose-dependent fashion. Importantly, we show that
      irradiation of cancer cells enhances their recognition by tumor-specific CD8+ T
      cells. The analysis of paired biopsies taken from a cohort of sarcoma patients
      before and after radiotherapy confirmed our findings and, in addition showed that
      irradiation resulted in higher infiltration by lymphocytes. Other forms of stress
      did not have an impact on the expression of CT-antigens or MHC-I. CONCLUSIONS:
      Our findings suggest that gamma-radiation promotes the immunological recognition
      of the tumor. We therefore propose that combining radiotherapy with treatments
      that support tumor specific immunity may result in increased therapeutic
      efficacy.

PMID- 22140551
TI  - Engineered single-domain antibodies with high protease resistance and thermal
      stability.
AB  - The extreme pH and protease-rich environment of the upper gastrointestinal tract
      is a major obstacle facing orally-administered protein therapeutics, including
      antibodies. Through protein engineering, several Clostridium difficile toxin A
      specific heavy chain antibody variable domains (V(H)Hs) were expressed with an
      additional disulfide bond by introducing Ala/Gly54Cys and Ile78Cys mutations.
      Mutant antibodies were compared to their wild-type counterparts with respect to
      expression yield, non-aggregation status, affinity for toxin A, circular
      dichroism (CD) structural signatures, thermal stability, protease resistance, and
      toxin A-neutralizing capacity. The mutant V(H)Hs were found to be well expressed,
      although with lower yields compared to wild-type counterparts, were non
      aggregating monomers, retained low nM affinity for toxin A, albeit the majority
      showed somewhat reduced affinity compared to wild-type counterparts, and were
      capable of in vitro toxin A neutralization in cell-based assays. Far-UV and near
      UV CD spectroscopy consistently showed shifts in peak intensity and selective
      peak minima for wild-type and mutant V(H)H pairs; however, the overall CD profile
      remained very similar. A significant increase in the thermal unfolding midpoint
      temperature was observed for all mutants at both neutral and acidic pH. Digestion
      of the V(H)Hs with the major gastrointestinal proteases, at biologically relevant
      concentrations, revealed a significant increase in pepsin resistance for all
      mutants and an increase in chymotrypsin resistance for the majority of mutants.
      Mutant V(H)H trypsin resistance was similar to that of wild-type V(H)Hs, although
      the trypsin resistance of one V(H)H mutant was significantly reduced. Therefore,
      the introduction of a second disulfide bond in the hydrophobic core not only
      increases V(H)H thermal stability at neutral pH, as previously shown, but also
      represents a generic strategy to increase V(H)H stability at low pH and impart
      protease resistance, with only minor perturbations in target binding affinities.
      These are all desirable characteristics for the design of protein-based oral
      therapeutics.

PMID- 22140552
TI  - Identification of prognostic genes for recurrent risk prediction in triple
      negative breast cancer patients in Taiwan.
AB  - Discrepancies in the prognosis of triple negative breast cancer exist between
      Caucasian and Asian populations. Yet, the gene signature of triple negative
      breast cancer specifically for Asians has not become available. Therefore, the
      purpose of this study is to construct a prediction model for recurrence of triple
      negative breast cancer in Taiwanese patients. Whole genome expression profiling
      of breast cancers from 185 patients in Taiwan from 1995 to 2008 was performed,
      and the results were compared to the previously published literature to detect
      differences between Asian and Western patients. Pathway analysis and Cox
      proportional hazard models were applied to construct a prediction model for the
      recurrence of triple negative breast cancer. Hierarchical cluster analysis showed
      that triple negative breast cancers from different races were in separate sub
      clusters but grouped in a bigger cluster. Two pathways, cAMP-mediated signaling
      and ephrin receptor signaling, were significantly associated with the recurrence
      of triple negative breast cancer. After using stepwise model selection from the
      combination of the initial filtered genes, we developed a prediction model based
      on the genes SLC22A23, PRKAG3, DPEP3, MORC2, GRB7, and FAM43A. The model had
      91.7% accuracy, 81.8% sensitivity, and 94.6% specificity under leave-one-out
      support vector regression. In this study, we identified pathways related to
      triple negative breast cancer and developed a model to predict its recurrence.
      These results could be used for assisting with clinical prognosis and warrant
      further investigation into the possibility of targeted therapy of triple negative
      breast cancer in Taiwanese patients.

PMID- 22140554
TI  - The role of histone methylation and H2A.Z occupancy during rapid activation of
      ethylene responsive genes.
AB  - Ethylene signaling pathway leads to rapid gene activation by two hierarchies of
      transcription factors with EIN3/EIL proteins as primary ones and ERF proteins as
      secondary ones. The role of chromatin modifications during the rapid gene
      activation is not known. In this work we studied trimethylated histone H3 lysine
      4 (H3K4me3) and lysine 27 (H3K27me3), two opposite histone methylation marks for
      gene activity, during the induction course of three ethylene-responsive genes
      (ERF1, AtERF14 and ChiB). We found that the three genes displayed different
      histone modification profiles before induction. After induction, H3K4me3 was
      increased in the 5' region and the gene body of ERF1, while H3K27me3 was
      decreased in the promoter of AtERF14. But the modification changes were later
      than the gene activation. Analysis of other rapidly inducible ERF genes confirmed
      the observation. In addition, histone H2A.Z occupancy on the three genes and the
      association of the H3K27me3-binding protein LHP1 with AtERF14 and ChiB were not
      affected by the inductive signal. However, the mutation of genes encoding H2A.Z
      and LHP1 attenuated and enhanced respectively the induction of target genes and
      altered H3K4me3. These results indicate that the induction of ethylene-responsive
      genes does not require immediate modulation of H3K4me3 and H3K27me3 and
      dissociation of LHP1 and H2A.Z from the targets, and suggest that the chromatin
      structure of the genes before induction is committed for transcriptional
      activation and that H3K4me3 is not required for ethylene-responsive gene
      activation, but may serve as a mark for gene activity.

PMID- 22140553
TI  - A systematic analysis on DNA methylation and the expression of both mRNA and
      microRNA in bladder cancer.
AB  - BACKGROUND: DNA methylation aberration and microRNA (miRNA) deregulation have
      been observed in many types of cancers. A systematic study of methylome and
      transcriptome in bladder urothelial carcinoma has never been reported.
      METHODOLOGY/PRINCIPAL FINDINGS: The DNA methylation was profiled by modified
      methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and
      miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and
      matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma
      patients. We found that a set of significantly enriched pathways disrupted in
      bladder urothelial carcinoma primarily related to "neurogenesis" and "cell
      differentiation" by integrated analysis of -omics data. Furthermore, we
      identified an intriguing collection of cancer-related genes that were deregulated
      at the levels of DNA methylation and mRNA expression, and we validated several of
      these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and
      Reverse Transcription qPCR in a panel of 33 bladder cancer samples.
      CONCLUSIONS/SIGNIFICANCE: We characterized the profiles between methylome and
      transcriptome in bladder urothelial carcinoma, identified a set of significantly
      enriched key pathways, and screened four aberrantly methylated and expressed
      genes. Conclusively, our findings shed light on a new avenue for basic bladder
      cancer research.

PMID- 22140555
TI  - Asymmetric activation of the primary motor cortex during observation of a mirror
      reflection of a hand.
AB  - Mirror therapy is an effective technique for pain relief and motor function
      recovery. It has been demonstrated that magnetic 20-Hz activity is induced in the
      primary motor cortex (M1) after median nerve stimulation and that the amount of
      the stimulus-induced 20-Hz activity is decreased when the M1 is activated. In the
      present study, we investigated how the image or the mirror reflection of a hand
      holding a pencil modulates the stimulus-induced 20-Hz activity in the M1.
      Neuromagnetic brain activity was recorded from 13 healthy right-handed subjects
      while they were either viewing directly their hand holding a pencil or viewing a
      mirror reflection of their hand holding a pencil. The 20-Hz activity in the left
      or the right M1 was examined after the right or the left median nerve
      stimulation, respectively, and the suppression of the stimulus-induced 20-Hz in
      the M1 by viewing directly one hand holding a pencil or by viewing the mirror
      image of the hand holding a pencil was assumed to indicate the activation of the
      M1. The results indicated that the M1 innervating the dominant hand was
      suppressed either by viewing directly the dominant hand holding a pencil or by
      viewing the mirror image of the non-dominant hand holding a pencil. On the other
      hand, the M1 innervating the non-dominant hand was activated by viewing the
      mirror image of the dominant hand holding a pencil, but was not activated by
      viewing directly the non-dominant hand holding a pencil. The M1 innervating
      either the dominant or the non-dominant hand, however, was not activated by
      viewing the hand on the side ipsilateral to the M1 examined or the mirror image
      of the hand on the side contralateral to the M1 exaimined. Such activation of the
      M1 might induce some therapeutic effects of mirror therapy.

PMID- 22140556
TI  - Fast and automatic activation of an abstract representation of money in the human
      ventral visual pathway.
AB  - Money, when used as an incentive, activates the same neural circuits as rewards
      associated with physiological needs. However, unlike physiological rewards,
      monetary stimuli are cultural artifacts: how are monetary stimuli identified in
      the first place? How and when does the brain identify a valid coin, i.e. a disc
      of metal that is, by social agreement, endowed with monetary properties? We took
      advantage of the changes in the Euro area in 2002 to compare neural responses to
      valid coins (Euros, Australian Dollars) with neural responses to invalid coins
      that have lost all monetary properties (French Francs, Finnish Marks). We show in
      magneto-encephalographic recordings, that the ventral visual pathway
      automatically distinguishes between valid and invalid coins, within only ~150 ms.
      This automatic categorization operates as well on coins subjects were familiar
      with as on unfamiliar coins. No difference between neural responses to scrambled
      controls could be detected. These results could suggest the existence of a
      generic, all-purpose neural representation of money that is independent of
      experience. This finding is reminiscent of a central assumption in economics,
      money fungibility, or the fact that a unit of money is substitutable to another.
      From a neural point of view, our findings may indicate that the ventral visual
      pathway, a system previously thought to analyze visual features such as shape or
      color and to be influenced by daily experience, could also able to use conceptual
      attributes such as monetary validity to categorize familiar as well as unfamiliar
      visual objects. The symbolic abilities of the posterior fusiform region suggested
      here could constitute an efficient neural substrate to deal with culturally
      defined symbols, independently of experience, which probably fostered money's
      cultural emergence and success.

PMID- 22140557
TI  - Temporal dissociation between myeloperoxidase (MPO)-modified LDL and MPO
      elevations during chronic sleep restriction and recovery in healthy young men.
AB  - OBJECTIVES: Many studies have evaluated the ways in which sleep disturbances may
      influence inflammation and the possible links of this effect to cardiovascular
      risk. Our objective was to investigate the effects of chronic sleep restriction
      and recovery on several blood cardiovascular biomarkers. METHODS AND RESULTS:
      Nine healthy male non-smokers, aged 22-29 years, were admitted to the Sleep
      Laboratory for 11 days and nights under continuous electroencephalogram
      polysomnography. The study consisted of three baseline nights of 8 hours sleep
      (from 11 pm to 7 am), five sleep-restricted nights, during which sleep was
      allowed only between 1 am and 6 am, and three recovery nights of 8 hours sleep
      (11 pm to 7 am). Myeloperoxidase-modified low-density lipoprotein levels
      increased during the sleep-restricted period indicating an oxidative stress. A
      significant increase in the quantity of slow-wave sleep was measured during the
      first recovery night. After this first recovery night, insulin-like growth factor
      1 levels increased and myeloperoxidase concentration peaked. CONCLUSIONS: We
      observed for the first time that sleep restriction and the recovery process are
      associated with differential changes in blood biomarkers of cardiovascular
      disease.

PMID- 22140558
TI  - Interkingdom gene transfer of a hybrid NPS/PKS from bacteria to filamentous
      Ascomycota.
AB  - Nonribosomal peptides (NRPs) and polyketides (PKs) are ecologically important
      secondary metabolites produced by bacteria and fungi using multidomain enzymes
      called nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs),
      respectively. Previous phylogenetic analyses of fungal NRPSs and PKSs have
      suggested that a few of these genes were acquired by fungi via horizontal gene
      transfer (HGT) from bacteria, including a hybrid NPS/PKS found in Cochliobolus
      heterostrophus (Dothideomycetes, Ascomycota). Here, we identify this hybrid gene
      in fungi representing two additional classes of Ascomycota (Aspergillus spp.,
      Microsporum canis, Arthroderma spp., and Trichophyton spp., Eurotiomycetes;
      Chaetomium spp. and Metarhizium spp., Sordariomycetes) and use phylogenetic
      analyses of the most highly conserved domains from NRPSs (adenylation (A) domain)
      and PKSs (ketoacyl synthase (KS) domain) to examine the hypothesis that the
      hybrid NPS7/PKS24 was acquired by fungi from bacteria via HGT relatively early in
      the evolution of the Pezizomycotina. Our results reveal a unique ancestry of the
      A domain and KS domain in the hybrid gene relative to known fungal NRPSs and
      PKSs, provide strong evidence for HGT of the hybrid gene from a putative
      bacterial donor in the Burkholderiales, and suggest the HGT event occurred early
      in the evolution of the filamentous Ascomycota.

PMID- 22140559
TI  - MUC1-C oncoprotein regulates glycolysis and pyruvate kinase M2 activity in cancer
      cells.
AB  - Aerobic glycolysis in cancer cells is regulated by multiple effectors that
      include Akt and pyruvate kinase M2 (PKM2). Mucin 1 (MUC1) is a heterodimeric
      glycoprotein that is aberrantly overexpressed by human breast and other
      carcinomas. Here we show that transformation of rat fibroblasts by the oncogenic
      MUC1-C subunit is associated with Akt-mediated increases in glucose uptake and
      lactate production, consistent with the stimulation of glycolysis. The results
      also demonstrate that the MUC1-C cytoplasmic domain binds directly to PKM2 at the
      B- and C-domains. Interaction between the MUC1-C cytoplasmic domain Cys-3 and the
      PKM2 C-domain Cys-474 was found to stimulate PKM2 activity. Conversely, epidermal
      growth factor receptor (EGFR)-mediated phosphorylation of the MUC1-C cytoplasmic
      domain on Tyr-46 conferred binding to PKM2 Lys-433 and inhibited PKM2 activity.
      In human breast cancer cells, silencing MUC1-C was associated with decreases in
      glucose uptake and lactate production, confirming involvement of MUC1-C in the
      regulation of glycolysis. In addition, EGFR-mediated phosphorylation of MUC1-C in
      breast cancer cells was associated with decreases in PKM2 activity. These
      findings indicate that the MUC1-C subunit regulates glycolysis and that this
      response is conferred in part by PKM2. Thus, the overexpression of MUC1-C
      oncoprotein in diverse human carcinomas could be of importance to the Warburg
      effect of aerobic glycolysis.

PMID- 22140560
TI  - Label-free 3D visualization of cellular and tissue structures in intact muscle
      with second and third harmonic generation microscopy.
AB  - Second and Third Harmonic Generation (SHG and THG) microscopy is based on optical
      effects which are induced by specific inherent physical properties of a specimen.
      As a multi-photon laser scanning approach which is not based on fluorescence it
      combines the advantages of a label-free technique with restriction of signal
      generation to the focal plane, thus allowing high resolution 3D reconstruction of
      image volumes without out-of-focus background several hundred micrometers deep
      into the tissue. While in mammalian soft tissues SHG is mostly restricted to
      collagen fibers and striated muscle myosin, THG is induced at a large variety of
      structures, since it is generated at interfaces such as refraction index changes
      within the focal volume of the excitation laser. Besides, colorants such as
      hemoglobin can cause resonance enhancement, leading to intense THG signals. We
      applied SHG and THG microscopy to murine (Mus musculus) muscles, an established
      model system for physiological research, to investigate their potential for label
      free tissue imaging. In addition to collagen fibers and muscle fiber
      substructure, THG allowed us to visualize blood vessel walls and erythrocytes as
      well as white blood cells adhering to vessel walls, residing in or moving through
      the extravascular tissue. Moreover peripheral nerve fibers could be clearly
      identified. Structure down to the nuclear chromatin distribution was visualized
      in 3D and with more detail than obtainable by bright field microscopy. To our
      knowledge, most of these objects have not been visualized previously by THG or
      any label-free 3D approach. THG allows label-free microscopy with inherent
      optical sectioning and therefore may offer similar improvements compared to
      bright field microscopy as does confocal laser scanning microscopy compared to
      conventional fluorescence microscopy.

PMID- 22140561
TI  - The Nubian Complex of Dhofar, Oman: an African middle stone age industry in
      Southern Arabia.
AB  - Despite the numerous studies proposing early human population expansions from
      Africa into Arabia during the Late Pleistocene, no archaeological sites have yet
      been discovered in Arabia that resemble a specific African industry, which would
      indicate demographic exchange across the Red Sea. Here we report the discovery of
      a buried site and more than 100 new surface scatters in the Dhofar region of Oman
      belonging to a regionally-specific African lithic industry--the late Nubian
      Complex--known previously only from the northeast and Horn of Africa during
      Marine Isotope Stage 5, ~128,000 to 74,000 years ago. Two optically stimulated
      luminescence age estimates from the open-air site of Aybut Al Auwal in Oman place
      the Arabian Nubian Complex at ~106,000 years ago, providing archaeological
      evidence for the presence of a distinct northeast African Middle Stone Age
      technocomplex in southern Arabia sometime in the first half of Marine Isotope
      Stage 5.

PMID- 22140562
TI  - Systematic comparison of three methods for fragmentation of long-range PCR
      products for next generation sequencing.
AB  - Next Generation Sequencing (NGS) technologies are gaining importance in the
      routine clinical diagnostic setting. It is thus desirable to simplify the
      workflow for high-throughput diagnostics. Fragmentation of DNA is a crucial step
      for preparation of template libraries and various methods are currently known.
      Here we evaluated the performance of nebulization, sonication and random
      enzymatic digestion of long-range PCR products on the results of NGS. All three
      methods produced high-quality sequencing libraries for the 454 platform. However,
      if long-range PCR products of different length were pooled equimolarly, sequence
      coverage drastically dropped for fragments below 3,000 bp. All three methods
      performed equally well with regard to overall sequence quality (PHRED) and read
      length. Enzymatic fragmentation showed highest consistency between three library
      preparations but performed slightly worse than sonication and nebulization with
      regard to insertions/deletions in the raw sequence reads. After filtering for
      homopolymer errors, enzymatic fragmentation performed best if compared to the
      results of classic Sanger sequencing. As the overall performance of all three
      methods was equal with only minor differences, a fragmentation method can be
      chosen solely according to lab facilities, feasibility and experimental design.

PMID- 22140563
TI  - Molecular determinants of magnolol targeting both RXRalpha and PPARgamma.
AB  - Nuclear receptors retinoic X receptor alpha (RXRalpha) and peroxisome
      proliferator activated receptor gamma (PPARgamma) function potently in metabolic
      diseases, and are both important targets for anti-diabetic drugs. Coactivation of
      RXRalpha and PPARgamma is believed to synergize their effects on glucose and
      lipid metabolism. Here we identify the natural product magnolol as a dual agonist
      targeting both RXRalpha and PPARgamma. Magnolol was previously reported to
      enhance adipocyte differentiation and glucose uptake, ameliorate blood glucose
      level and prevent development of diabetic nephropathy. Although magnolol can bind
      and activate both of these two nuclear receptors, the transactivation assays
      indicate that magnolol exhibits biased agonism on the transcription of PPAR
      response element (PPRE) mediated by RXRalpha:PPARgamma heterodimer, instead of
      RXR-response element (RXRE) mediated by RXRalpha:RXRalpha homodimer. To further
      elucidate the molecular basis for magnolol agonism, we determine both the co
      crystal structures of RXRalpha and PPARgamma ligand-binding domains (LBDs) with
      magnolol. Structural analyses reveal that magnolol adopts its two 5-allyl-2
      hydroxyphenyl moieties occupying the acidic and hydrophobic cavities of RXRalpha
      L-shaped ligand-binding pocket, respectively. While, two magnolol molecules
      cooperatively accommodate into PPARgamma Y-shaped ligand-binding pocket. Based on
      these two complex structures, the key interactions for magnolol activating
      RXRalpha and PPARgamma are determined. As the first report on the dual agonist
      targeting RXRalpha and PPARgamma with receptor-ligand complex structures, our
      results are thus expected to help inspect the potential pharmacological mechanism
      for magnolol functions, and supply useful hits for nuclear receptor multi-target
      ligand design.

PMID- 22140564
TI  - The hector G-protein coupled receptor is required in a subset of fruitless
      neurons for male courtship behavior.
AB  - Male courtship behavior in Drosophila melanogaster is controlled by two main
      regulators, fruitless (fru) and doublesex (dsx). Their sex-specific expression in
      brain neurons has been characterized in detail, but little is known about the
      downstream targets of the sex-specific FRU and DSX proteins and how they specify
      the function of these neurons. While sexual dimorphism in the number and
      connections of fru and dsx expressing neurons has been observed, a majority of
      the neurons that express the two regulators are present in both sexes. This poses
      the question which molecules define the sex-specific function of these neurons.
      Signaling molecules are likely to play a significant role. We have identified a
      predicted G-protein coupled receptor (GPCR), CG4395, that is required for male
      courtship behavior. The courtship defect in the mutants can be rescued by
      expression of the wildtype protein in fru neurons of adult males. The GPCR is
      expressed in a subset of fru-positive antennal glomeruli that have previously
      been shown to be essential for male courtship. Expression of 4395-RNAi in GH146
      projection neurons lowers courtship. This suggests that signaling through the
      CG4395 GPCR in this subset of fru neurons is critical for male courtship
      behavior.

PMID- 22140565
TI  - The cultural evolution of democracy: saltational changes in a political regime
      landscape.
AB  - Transitions to democracy are most often considered the outcome of historical
      modernization processes. Socio-economic changes, such as increases in per capita
      GNP, education levels, urbanization and communication, have traditionally been
      found to be correlates or 'requisites' of democratic reform. However, transition
      times and the number of reform steps have not been studied comprehensively. Here
      we show that historically, transitions to democracy have mainly occurred through
      rapid leaps rather than slow and incremental transition steps, with a median time
      from autocracy to democracy of 2.4 years, and overnight in the reverse direction.
      Our results show that autocracy and democracy have acted as peaks in an
      evolutionary landscape of possible modes of institutional arrangements. Only
      scarcely have there been slow incremental transitions. We discuss our results in
      relation to the application of phylogenetic comparative methods in cultural
      evolution and point out that the evolving unit in this system is the
      institutional arrangement, not the individual country which is instead better
      regarded as the 'host' for the political system.

PMID- 22140566
TI  - Neurotrophic effect of citrus 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone:
      promotion of neurite outgrowth via cAMP/PKA/CREB pathway in PC12 cells.
AB  - 5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF), a hydroxylated
      polymethoxyflavone, is found exclusively in the Citrus genus, particularly in the
      peels of sweet orange. In this research, we report the first investigation of the
      neurotrophic effects and mechanism of 5-OH-HxMF in PC12 pheochromocytoma cells.
      We found that 5-OH-HxMF can effectively induce PC12 neurite outgrowth accompanied
      with the expression of neuronal differentiation marker protein growth-associated
      protein-43(GAP-43). 5-OH-HxMF caused the enhancement of cyclic AMP response
      element binding protein (CREB) phosphorylation, c-fos gene expression and CRE
      mediated transcription, which was inhibited by 2-naphthol AS-E phosphate (KG
      501), a specific antagonist for the CREB-CBP complex formation. Moreover, 5-OH
      HxMF-induced both CRE transcription activity and neurite outgrowth were inhibited
      by adenylate cyclase and protein kinase A (PKA) inhibitor, but not MEK1/2,
      protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K) or
      calcium/calmodulin-dependent protein kinase (CaMK) inhibitor. Consistently, 5-OH
      HxMF treatment increased the intracellular cAMP level and downstream component,
      PKA activity. We also found that addition of K252a, a TrKA antagonist,
      significantly inhibited NGF- but not 5-OH-HxMF-induced neurite outgrowth. These
      results reveal for the first time that 5-OH-HxMF is an effective neurotrophic
      agent and its effect is mainly through a cAMP/PKA-dependent, but TrKA
      independent, signaling pathway coupling with CRE-mediated gene transcription. A
      PKC-dependent and CREB-independent pathway was also involved in its neurotrophic
      action.

PMID- 22140567
TI  - Progressive, transgenerational changes in offspring phenotype and epigenotype
      following nutritional transition.
AB  - Induction of altered phenotypes during development in response to environmental
      input involves epigenetic changes. Phenotypic traits can be passed between
      generations by a variety of mechanisms, including direct transmission of
      epigenetic states or by induction of epigenetic marks de novo in each generation.
      To distinguish between these possibilities we measured epigenetic marks over four
      generations in rats exposed to a sustained environmental challenge. Dietary
      energy was increased by 25% at conception in F0 female rats and maintained at
      this level to generation F3. F0 dams showed higher pregnancy weight gain, but
      lower weight gain and food intake during lactation than F1 and F2 dams. On
      gestational day 8, fasting plasma glucose concentration was higher and beta
      hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by
      decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARalpha and
      carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was
      inversely related to the methylation of specific CpG dinucleotides in its
      promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression
      increased and methylation of its promoter decreased from F1 to F3 generations.
      These data suggest that the regulation of energy metabolism during pregnancy and
      lactation within a generation is influenced by the maternal phenotype in the
      preceding generation and the environment during the current pregnancy. The
      transgenerational effects on phenotype were associated with altered DNA
      methylation of specific genes in a manner consistent with induction de novo of
      epigenetic marks in each generation.

PMID- 22140568
TI  - Inducible gene manipulations in brain serotonergic neurons of transgenic rats.
AB  - The serotonergic (5-HT) system has been implicated in various physiological
      processes and neuropsychiatric disorders, but in many aspects its role in normal
      and pathologic brain function is still unclear. One reason for this might be the
      lack of appropriate animal models which can address the complexity of
      physiological and pathophysiological 5-HT functioning. In this respect, rats
      offer many advantages over mice as they have been the animal of choice for
      sophisticated neurophysiological and behavioral studies. However, only recently
      technologies for the targeted and tissue specific modification of rat genes - a
      prerequisite for a detailed study of the 5-HT system - have been successfully
      developed. Here, we describe a rat transgenic system for inducible gene
      manipulations in 5-HT neurons. We generated a Cre driver line consisting of a
      tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2
      regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was
      detected in four transgenic TPH2-CreERT2 rat founder lines. For functional
      analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG
      loxP.EGFP), in which EGFP is expressed after Cre-mediated removal of a loxP
      flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre
      reporter line and demonstrate its applicability for monitoring Cre-mediated
      recombination in all major neuronal subpopulations of the rat brain. Upon
      tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show
      selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen
      administration, EGFP is only expressed in few 5-HT neurons which confirms minimal
      background recombination. This 5-HT neuron specific CreERT2 line allows Cre
      mediated, inducible gene deletion or gene overexpression in transgenic rats which
      provides new opportunities to decipher the complex functions of the mammalian
      serotonergic system.

PMID- 22140569
TI  - New variants and age shift to high fatality groups contribute to severe
      successive waves in the 2009 influenza pandemic in Taiwan.
AB  - Past influenza pandemics have been characterized by the signature feature of
      multiple waves. However, the reasons for multiple waves in a pandemic are not
      understood. Successive waves in the 2009 influenza pandemic, with a sharp
      increase in hospitalized and fatal cases, occurred in Taiwan during the winter of
      2010. In this study, we sought to discover possible contributors to the multiple
      waves in this influenza pandemic. We conducted a large-scale analysis of 4703
      isolates in an unbiased manner to monitor the emergence, dominance and
      replacement of various variants. Based on the data from influenza surveillance
      and epidemic curves of each variant clade, we defined virologically and
      temporally distinct waves of the 2009 pandemic in Taiwan from May 2009 to April
      2011 as waves 1 and 2, an interwave period and wave 3. Except for wave 3, each
      wave was dominated by one distinct variant. In wave 3, three variants emerged and
      co-circulated, and formed distinct phylogenetic clades, based on the
      hemagglutinin (HA) genes and other segments. The severity of influenza was
      represented as the case fatality ratio (CFR) in the hospitalized cases. The CFRs
      in waves 1 and 2, the interwave period and wave 3 were 6.4%, 5.1%, 15.2% and
      9.8%, respectively. The results highlight the association of virus evolution and
      variable influenza severity. Further analysis revealed that the major affected
      groups were shifted in the waves to older individuals, who had higher age
      specific CFRs. The successive pandemic waves create challenges for the strategic
      preparedness of health authorities and make the pandemic uncertain and variable.
      Our findings indicate that the emergence of new variants and age shift to high
      fatality groups might contribute potentially to the occurrence of successive
      severe pandemic waves and offer insights into the adjustment of national
      responses to mitigate influenza pandemics.

PMID- 22140570
TI  - Genetic control of the variable innate immune response to asymptomatic
      bacteriuria.
AB  - The severity of urinary tract infection (UTI) reflects the quality and magnitude
      of the host response. While strong local and systemic innate immune activation
      occurs in patients with acute pyelonephritis, the response to asymptomatic
      bacteriuria (ABU) is low. The immune response repertoire in ABU has not been
      characterized, due to the inherent problem to distinguish bacterial differences
      from host-determined variation. In this study, we investigated the host response
      to ABU and genetic variants affecting innate immune signaling and UTI
      susceptibility. Patients were subjected to therapeutic urinary tract inoculation
      with E. coli 83972 to ensure that they were exposed to the same E. coli strain.
      The innate immune response repertoire was characterized in urine samples,
      collected from each patient before and after inoculation with bacteria or PBS, if
      during the placebo arm of the study. Long-term E. coli 83972 ABU was established
      in 23 participants, who were followed for up to twelve months and the innate
      immune response was quantified in 233 urine samples. Neutrophil numbers increased
      in all but two patients and in an extended urine cytokine/chemokine analysis (31
      proteins), the chemoattractants IL-8 and GRO-alpha, RANTES, Eotaxin-1 and MCP-1,
      the T cell chemoattractant and antibacterial peptide IP-10, inflammatory
      regulators IL-1-alpha and sIL-1RA and the T lymphocyte/dendritic cell product sIL
      2Ralpha were detected and variably increased, compared to sterile samples. IL-6,
      which is associated with symptomatic UTI, remained low and numerous specific
      immune mediators were not detected. The patients were also genotyped for UTI
      associated IRF3 and TLR4 promoter polymorphisms. Patients with ABU associated
      TLR4 polymorphisms had low neutrophil numbers, IL-6, IP-10, MCP-1 and sIL-2Ralpha
      concentrations. Patients with the ABU-associated IRF3 genotype had lower
      neutrophils, IL-6 and MCP-1 responses than the remaining group. The results
      suggest that the host-specific, low immune response to ABU mainly includes innate
      immune mediators and that host genetics directly influence the magnitude of this
      response.

PMID- 22140571
TI  - Involvement of a velvet protein FgVeA in the regulation of asexual development,
      lipid and secondary metabolisms and virulence in Fusarium graminearum.
AB  - The velvet protein, VeA, is involved in the regulation of diverse cellular
      processes. In this study, we explored functions of FgVeA in the wheat head blight
      pathogen, Fusarium graminearum,using a gene replacement strategy. The FgVEA
      deletion mutant exhibited a reduction in aerial hyphae formation, hydrophobicity,
      and deoxynivalenol (DON) biosynthesis. Deletion of FgVEA gene led to an increase
      in conidial production, but a delay in conidial germination. Pathogencity assays
      showed that the mutant was impaired in virulence on flowering wheat head.
      Sensitivity tests to various stresses exhibited that the FgVEA deletion mutant
      showed increased resistance to osmotic stress and cell wall-damaging agents, but
      increased sensitivity to iprodione and fludioxonil fungicides. Ultrastructural
      and histochemical analyses revealed that conidia of FgVeA deletion mutant
      contained an unusually high number of large lipid droplets, which is in agreement
      with the observation that the mutant accumulated a higher basal level of glycerol
      than the wild-type progenitor. Serial analysis of gene expression (SAGE) in the
      FgVEA mutant confirmed that FgVeA was involved in various cellular processes.
      Additionally, six proteins interacting with FgVeA were identified by yeast two
      hybrid assays in current study. These results indicate that FgVeA plays a
      critical role in a variety of cellular processes in F. graminearum.

PMID- 22140572
TI  - Dynamic changes in brain functional connectivity during concurrent dual-task
      performance.
AB  - This study investigated the spatial, spectral, temporal and functional
      proprieties of functional brain connections involved in the concurrent execution
      of unrelated visual perception and working memory tasks. Electroencephalography
      data was analysed using a novel data-driven approach assessing source coherence
      at the whole-brain level. Three connections in the beta-band (18-24 Hz) and one
      in the gamma-band (30-40 Hz) were modulated by dual-task performance. Beta
      coherence increased within two dorsofrontal-occipital connections in dual-task
      conditions compared to the single-task condition, with the highest coherence seen
      during low working memory load trials. In contrast, beta-coherence in a
      prefrontal-occipital functional connection and gamma-coherence in an inferior
      frontal-occipitoparietal connection was not affected by the addition of the
      second task and only showed elevated coherence under high working memory load.
      Analysis of coherence as a function of time suggested that the dorsofrontal
      occipital beta-connections were relevant to working memory maintenance, while the
      prefrontal-occipital beta-connection and the inferior frontal-occipitoparietal
      gamma-connection were involved in top-down control of concurrent visual
      processing. The fact that increased coherence in the gamma-connection, from low
      to high working memory load, was negatively correlated with faster reaction time
      on the perception task supports this interpretation. Together, these results
      demonstrate that dual-task demands trigger non-linear changes in functional
      interactions between frontal-executive and occipitoparietal-perceptual cortices.

PMID- 22140573
TI  - Physical activity and natural anti-VIP antibodies: potential role in breast and
      prostate cancer therapy.
AB  - BACKGROUND: There is convincing evidence from numerous clinical and
      epidemiological studies that physical activity can reduce the risk for breast and
      prostate cancer. The biological mechanisms underlying this phenomenon remain
      elusive. Herein we suggest a role for naturally produced antibodies reactive with
      the vasoactive intestinal peptide (VIP) in the suppression of breast and prostate
      cancer, which we believe could offer a possible molecular mechanism underlying
      control of these cancers by physical exercise. METHODOLOGY AND RESULTS: We found
      that sera from individuals having breast and prostate cancers have decreased
      titers of VIP natural antibodies as demonstrated by a lower reactivity against
      peptide NTM1, having similar informational and structural properties as VIP. In
      contrast, sera collected from elite athletes, exhibited titers of natural NTM1
      reactive antibodies that are significantly increased, suggesting that physical
      activity boosts production of these antibodies. SIGNIFICANCE: Presented results
      suggest that physical exercise stimulates production of natural anti-VIP
      antibodies and likely results in suppression of VIP. This, in turn, may play a
      protective role against breast and prostate cancers. Physical exercise should be
      further investigated as a potential tool in the treatment of these diseases.

PMID- 22140574
TI  - Efficient production of HIV-1 virus-like particles from a mammalian expression
      vector requires the N-terminal capsid domain.
AB  - It is now well accepted that the structural protein Pr55(Gag) is sufficient by
      itself to produce HIV-1 virus-like particles (VLPs). This polyprotein precursor
      contains different domains including matrix, capsid, SP1, nucleocapsid, SP2 and
      p6. In the present study, we wanted to determine by mutagenesis which region(s)
      is essential to the production of VLPs when Pr55(Gag) is inserted in a mammalian
      expression vector, which allows studying the protein of interest in the absence
      of other viral proteins. To do so, we first studied a minimal Pr55(Gag) sequence
      called Gag min that was used previously. We found that Gag min fails to produce
      VLPs when expressed in an expression vector instead of within a molecular clone.
      This failure occurs early in the cell at the assembly of viral proteins. We then
      generated a series of deletion and substitution mutants, and examined their
      ability to produce VLPs by combining biochemical and microscopic approaches. We
      demonstrate that the matrix region is not necessary, but that the efficiency of
      VLP production depends strongly on the presence of its basic region. Moreover,
      the presence of the N-terminal domain of capsid is required for VLP production
      when Gag is expressed alone. These findings, combined with previous observations
      indicating that HIV-1 Pr55(Gag)-derived VLPs act as potent stimulators of innate
      and acquired immunity, make the use of this strategy worth considering for
      vaccine development.

PMID- 22140575
TI  - Comparative analysis of human protein-coding and noncoding RNAs between brain and
      10 mixed cell lines by RNA-Seq.
AB  - In their expression process, different genes can generate diverse functional
      products, including various protein-coding or noncoding RNAs. Here, we
      investigated the protein-coding capacities and the expression levels of their
      isoforms for human known genes, the conservation and disease association of long
      noncoding RNAs (ncRNAs) with two transcriptome sequencing datasets from human
      brain tissues and 10 mixed cell lines. Comparative analysis revealed that about
      two-thirds of the genes expressed between brain and cell lines are the same, but
      less than one-third of their isoforms are identical. Besides those genes
      specially expressed in brain and cell lines, about 66% of genes expressed in
      common encoded different isoforms. Moreover, most genes dominantly expressed one
      isoform and some genes only generated protein-coding (or noncoding) RNAs in one
      sample but not in another. We found 282 human genes could encode both protein
      coding and noncoding RNAs through alternative splicing in the two samples. We
      also identified more than 1,000 long ncRNAs, and most of those long ncRNAs
      contain conserved elements across either 46 vertebrates or 33 placental mammals
      or 10 primates. Further analysis showed that some long ncRNAs differentially
      expressed in human breast cancer or lung cancer, several of those differentially
      expressed long ncRNAs were validated by RT-PCR. In addition, those validated
      differentially expressed long ncRNAs were found significantly correlated with
      certain breast cancer or lung cancer related genes, indicating the important
      biological relevance between long ncRNAs and human cancers. Our findings reveal
      that the differences of gene expression profile between samples mainly result
      from the expressed gene isoforms, and highlight the importance of studying genes
      at the isoform level for completely illustrating the intricate transcriptome.

PMID- 22140576
TI  - Peroxisome proliferator-activated receptor-gamma agonists suppress tissue factor
      overexpression in rat balloon injury model with paclitaxel infusion.
AB  - The role and underlying mechanisms of rosiglitazone, a peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) agonist, on myocardial infarction are
      poorly understood. We investigated the effects of this PPAR-gamma agonist on the
      expression of tissue factor (TF), a primary molecule for thrombosis, and
      elucidated its underlying mechanisms. The PPAR-gamma agonist inhibited TF
      expression in response to TNF-alpha in human umbilical vein endothelial cells,
      human monocytic leukemia cell line, and human umbilical arterial smooth muscle
      cells. The overexpression of TF was mediated by increased phosphorylation of
      mitogen-activated protein kinase (MAPK), which was blocked by the PPAR-gamma
      agonist. The effective MAPK differed depending on each cell type. Luciferase and
      ChIP assays showed that transcription factor, activator protein-1 (AP-1), was a
      pivotal target of the PPAR-gamma agonist to lower TF transcription. Intriguingly,
      two main drugs for drug-eluting stent, paclitaxel or rapamycin, significantly
      exaggerated thrombin-induced TF expression, which was also effectively blocked by
      the PPAR-gamma agonist in all cell types. This PPAR-gamma agonist did not impair
      TF pathway inhibitor (TFPI) in three cell types. In rat balloon injury model
      (Sprague-Dawley rats, n = 10/group) with continuous paclitaxel infusion, the PPAR
      gamma agonist attenuated TF expression by 70+/-5% (n = 4; P<0.0001) in injured
      vasculature. Taken together, rosiglitazone reduced TF expression in three
      critical cell types involved in vascular thrombus formation via MAPK and AP-1
      inhibitions. Also, this PPAR-gamma agonist reversed the paclitaxel-induced
      aggravation of TF expression, which suggests a possibility that the benefits
      might outweigh its risks in a group of patients with paclitaxel-eluting stent
      implanted.

PMID- 22140577
TI  - Simultaneous mutations in multi-viral proteins are required for soybean mosaic
      virus to gain virulence on soybean genotypes carrying different R genes.
AB  - BACKGROUND: Genetic resistance is the most effective and sustainable approach to
      the control of plant pathogens that are a major constraint to agriculture
      worldwide. In soybean, three dominant R genes, i.e., Rsv1, Rsv3 and Rsv4, have
      been identified and deployed against Soybean mosaic virus (SMV) with strain
      specificities. Molecular identification of virulent determinants of SMV on these
      resistance genes will provide essential information for the proper utilization of
      these resistance genes to protect soybean against SMV, and advance knowledge of
      virus-host interactions in general. METHODOLOGY/PRINCIPAL FINDINGS: To study the
      gain and loss of SMV virulence on all the three resistance loci, SMV strains G7
      and two G2 isolates L and LRB were used as parental viruses. SMV chimeras and
      mutants were created by partial genome swapping and point mutagenesis and then
      assessed for virulence on soybean cultivars PI96983 (Rsv1), L-29 (Rsv3), V94-5152
      (Rsv4) and Williams 82 (rsv). It was found that P3 played an essential role in
      virulence determination on all three resistance loci and CI was required for
      virulence on Rsv1- and Rsv3-genotype soybeans. In addition, essential mutations
      in HC-Pro were also required for the gain of virulence on Rsv1-genotype soybean.
      To our best knowledge, this is the first report that CI and P3 are involved in
      virulence on Rsv1- and Rsv3-mediated resistance, respectively.
      CONCLUSIONS/SIGNIFICANCE: Multiple viral proteins, i.e., HC-Pro, P3 and CI, are
      involved in virulence on the three resistance loci and simultaneous mutations at
      essential positions of different viral proteins are required for an avirulent SMV
      strain to gain virulence on all three resistance loci. The likelihood of such
      mutations occurring naturally and concurrently on multiple viral proteins is low.
      Thus, incorporation of all three resistance genes in a soybean cultivar through
      gene pyramiding may provide durable resistance to SMV.

PMID- 22140578
TI  - Hole-in-one mutant phenotypes link EGFR/ERK signaling to epithelial tissue repair
      in Drosophila.
AB  - BACKGROUND: Epithelia act as physical barriers protecting living organisms and
      their organs from the surrounding environment. Simple epithelial tissues have the
      capacity to efficiently repair wounds through a resealing mechanism. The known
      molecular mechanisms underlying this process appear to be conserved in both
      vertebrates and invertebrates, namely the involvement of the transcription
      factors Grainy head (Grh) and Fos. In Drosophila, Grh and Fos lead to the
      activation of wound response genes required for epithelial repair. ERK is
      upstream of this pathway and known to be one of the first kinases to be activated
      upon wounding. However, it is still unclear how ERK activation contributes to a
      proper wound response and which molecular mechanisms regulate its activation.
      METHODOLOGY/PRINCIPAL FINDINGS: In a previous screen, we isolated mutants with
      defects in wound healing. Here, we describe the role of one of these genes, hole
      in-one (holn1), in the wound healing process. Holn1 is a GYF domain containing
      protein that we found to be required for the activation of several Grh and Fos
      regulated wound response genes at the wound site. We also provide evidence
      suggesting that Holn1 may be involved in the Ras/ERK signaling pathway, by acting
      downstream of ERK. Finally, we show that wound healing requires the function of
      EGFR and ERK signaling. CONCLUSIONS/SIGNIFICANCE: Based on these data, we
      conclude that holn1 is a novel gene required for a proper wound healing response.
      We further propose and discuss a model whereby Holn1 acts downstream of EGFR and
      ERK signaling in the Grh/Fos mediated wound closure pathway.

PMID- 22140579
TI  - Genetic complexity of fusidic acid-resistant small colony variants (SCV) in
      Staphylococcus aureus.
AB  - FusE mutants are fusidic acid-resistant small colony variants (SCVs) of
      Staphylococcus aureus that can be selected with aminoglycosides. All FusE SCVs
      have mutations in rplF, encoding ribosomal protein L6. However, individual FusE
      mutants including some with the same mutation in rplF display auxotrophy for
      either hemin or menadione, suggesting that additional mutations are involved.
      Here we show that FusE SCVs can be divided into three genetic sub-groups and that
      some carry an additional mutation, in one of the genes required for hemin
      biosynthesis, or in one of the genes required for menadione biosynthesis.
      Reversion analysis and genome sequencing support the hypothesis that these
      combinations of mutations in the rplF, hem, and/or men genes can account for the
      SCV and auxotrophic phenotypes of FusE mutants.

PMID- 22140580
TI  - Growth hormone promotes hair cell regeneration in the zebrafish (Danio rerio)
      inner ear following acoustic trauma.
AB  - BACKGROUND: Previous microarray analysis showed that growth hormone (GH) was
      significantly upregulated following acoustic trauma in the zebrafish (Danio
      rerio) ear suggesting that GH may play an important role in the process of
      auditory hair cell regeneration. Our objective was to examine the effects of
      exogenous and endogenous GH on zebrafish inner ear epithelia following acoustic
      trauma. METHODOLOGY/PRINCIPAL FINDINGS: We induced auditory hair cell damage by
      exposing zebrafish to acoustic overstimulation. Fish were then injected
      intraperitoneally with either carp GH or buffer, and placed in a recovery tank
      for either one or two days. Phalloidin-, bromodeoxyuridine (BrdU)-, and TUNEL
      labeling were used to examine hair cell densities, cell proliferation, and
      apoptosis, respectively. Two days post-trauma, saccular hair cell densities in GH
      treated fish were similar to that of baseline controls, whereas buffer-injected
      fish showed significantly reduced densities of hair cell bundles. Cell
      proliferation was greater and apoptosis reduced in the saccules, lagenae, and
      utricles of GH-treated fish one day following trauma compared to controls.
      Fluorescent in situ hybridization (FISH) was used to examine the localization of
      GH mRNA in the zebrafish ear. At one day post-trauma, GH mRNA expression appeared
      to be localized perinuclearly around erythrocytes in the blood vessels of the
      inner ear epithelia. In order to examine the effects of endogenous GH on the
      process of cell proliferation in the ear, a GH antagonist was injected into
      zebrafish immediately following acoustic trauma, resulting in significantly
      decreased cell proliferation one day post-trauma in all three zebrafish inner ear
      end organs. CONCLUSIONS/SIGNIFICANCE: Our results show that exogenous GH promotes
      post-trauma auditory hair cell regeneration in the zebrafish ear through
      stimulating proliferation and suppressing apoptosis, and that endogenous GH
      signals are present in the zebrafish ear during the process of auditory hair cell
      regeneration.

PMID- 22140581
TI  - Nuclear progesterone receptors are up-regulated by estrogens in neurons and
      radial glial progenitors in the brain of zebrafish.
AB  - In rodents, there is increasing evidence that nuclear progesterone receptors are
      transiently expressed in many regions of the developing brain, notably outside
      the hypothalamus. This suggests that progesterone and/or its metabolites could be
      involved in functions not related to reproduction, particularly in
      neurodevelopment. In this context, the adult fish brain is of particular
      interest, as it exhibits constant growth and high neurogenic activity that is
      supported by radial glia progenitors. However, although synthesis of
      neuroprogestagens has been documented recently in the brain of zebrafish,
      information on the presence of progesterone receptors is very limited. In
      zebrafish, a single nuclear progesterone receptor (pgr) has been cloned and
      characterized. Here, we demonstrate that this pgr is widely distributed in all
      regions of the zebrafish brain. Interestingly, we show that Pgr is strongly
      expressed in radial glial cells and more weakly in neurons. Finally, we present
      evidence, based on quantitative PCR and immunohistochemistry, that nuclear
      progesterone receptor mRNA and proteins are upregulated by estrogens in the brain
      of adult zebrafish. These data document for the first time the finding that
      radial glial cells are preferential targets for peripheral progestagens and/or
      neuroprogestagens. Given the crucial roles of radial glial cells in adult
      neurogenesis, the potential effects of progestagens on their activity and the
      fate of daughter cells require thorough investigation.

PMID- 22140582
TI  - Mifepristone prevents stress-induced apoptosis in newborn neurons and increases
      AMPA receptor expression in the dentate gyrus of C57/BL6 mice.
AB  - Chronic stress produces sustained elevation of corticosteroid levels, which is
      why it is considered one of the most potent negative regulators of adult
      hippocampal neurogenesis (AHN). Several mood disorders are accompanied by
      elevated glucocorticoid levels and have been linked to alterations in AHN, such
      as major depression (MD). Nevertheless, the mechanism by which acute stress
      affects the maturation of neural precursors in the dentate gyrus is poorly
      understood. We analyzed the survival and differentiation of 1 to 8 week-old cells
      in the dentate gyrus of female C57/BL6 mice following exposure to an acute
      stressor (the Porsolt or forced swimming test). Furthermore, we evaluated the
      effects of the glucocorticoid receptor (GR) antagonist mifepristone on the cell
      death induced by the Porsolt test. Forced swimming induced selective apoptotic
      cell death in 1 week-old cells, an effect that was abolished by pretreatment with
      mifepristone. Independent of its antagonism of GR, mifepristone also induced an
      increase in the percentage of 1 week-old cells that were AMPA(+). We propose that
      the induction of AMPA receptor expression in immature cells may mediate the
      neuroprotective effects of mifepristone, in line with the proposed antidepressant
      effects of AMPA receptor potentiators.

PMID- 22140583
TI  - A genetic signature of spina bifida risk from pathway-informed comprehensive gene
      variant analysis.
AB  - Despite compelling epidemiological evidence that folic acid supplements reduce
      the frequency of neural tube defects (NTDs) in newborns, common variant
      association studies with folate metabolism genes have failed to explain the
      majority of NTD risk. The contribution of rare alleles as well as genetic
      interactions within the folate pathway have not been extensively studied in the
      context of NTDs. Thus, we sequenced the exons in 31 folate-related genes in a 480
      member NTD case-control population to identify the full spectrum of allelic
      variation and determine whether rare alleles or obvious genetic interactions
      within this pathway affect NTD risk. We constructed a pathway model,
      predetermined independent of the data, which grouped genes into coherent sets
      reflecting the distinct metabolic compartments in the folate/one-carbon pathway
      (purine synthesis, pyrimidine synthesis, and homocysteine recycling to
      methionine). By integrating multiple variants based on these groupings, we
      uncovered two provocative, complex genetic risk signatures. Interestingly, these
      signatures differed by race/ethnicity: a Hispanic risk profile pointed to
      alterations in purine biosynthesis, whereas that in non-Hispanic whites
      implicated homocysteine metabolism. In contrast, parallel analyses that focused
      on individual alleles, or individual genes, as the units by which to assign risk
      revealed no compelling associations. These results suggest that the ability to
      layer pathway relationships onto clinical variant data can be uniquely
      informative for identifying genetic risk as well as for generating mechanistic
      hypotheses. Furthermore, the identification of ethnic-specific risk signatures
      for spina bifida resonated with epidemiological data suggesting that the
      underlying pathogenesis may differ between Hispanic and non-Hispanic groups.

PMID- 22140584
TI  - Smart drugs "as common as coffee": media hype about neuroenhancement.
AB  - BACKGROUND: The use of prescription drugs to improve cognitive functioning in
      normal persons--neuroenhancement"--has gained recent attention from bioethicists
      and neuroscientists. Enthusiasts claim that the practice is widespread and
      increasing, and has many potential benefits; however recent evidence provides
      weak support for these claims. In this study we explored how the newsprint media
      portrays neuroenhancement. AIMS: We conducted an empirical study of media
      reporting of neuroenhancement to explore: media portrayals of the prevalence of
      neuroenhancement; the types of evidence used by the media to support claims about
      its prevalence; and, the possible benefits and risks of neuroenhancement
      mentioned in these media articles. METHODS: Using the Factiva database, we found
      142 newspaper articles about the non-medical use prescription drugs for
      neuroenhancement for the period 2008-2010. We conducted a thematic content
      analysis of how articles portrayed the prevalence of neuroenhancement; what type
      of evidence they used in support; and, the potential benefits and risks/side
      effects of neuroenhancement that were mentioned. RESULTS: 87% of media articles
      mentioned the prevalence of neuroenhancement, and 94% portrayed it as common,
      increasing or both. 66% referred to the academic literature to support these
      claims and 44% either named an author or a journal. 95% of articles mentioned at
      least one possible benefit of using prescription drugs for neuroenhancement, but
      only 58% mentioned any risks/side effects. 15% questioned the evidence for
      efficacy of prescription drugs to produce benefits to users. CONCLUSIONS: News
      media articles mentioned the possible benefits of using drugs for
      neuroenhancement more than the potential risks/side effects, and the main source
      for media claims that neuroenhancement is common and increasingly widespread has
      been reports from the academic literature that provide weak support for this
      claim. We urge journalists and researchers to be cautious in their portrayal of
      the non-medical use of drugs for neuroenhancement.

PMID- 22140585
TI  - The NIH-NIAID Filariasis Research Reagent Resource Center.
AB  - Filarial worms cause a variety of tropical diseases in humans; however, they are
      difficult to study because they have complex life cycles that require arthropod
      intermediate hosts and mammalian definitive hosts. Research efforts in
      industrialized countries are further complicated by the fact that some filarial
      nematodes that cause disease in humans are restricted in host specificity to
      humans alone. This potentially makes the commitment to research difficult,
      expensive, and restrictive. Over 40 years ago, the United States National
      Institutes of Health-National Institute of Allergy and Infectious Diseases (NIH
      NIAID) established a resource from which investigators could obtain various
      filarial parasite species and life cycle stages without having to expend the
      effort and funds necessary to maintain the entire life cycles in their own
      laboratories. This centralized resource (The Filariasis Research Reagent Resource
      Center, or FR3) translated into cost savings to both NIH-NIAID and to principal
      investigators by freeing up personnel costs on grants and allowing investigators
      to divert more funds to targeted research goals. Many investigators, especially
      those new to the field of tropical medicine, are unaware of the scope of
      materials and support provided by the FR3. This review is intended to provide a
      short history of the contract, brief descriptions of the fiilarial species and
      molecular resources provided, and an estimate of the impact the resource has had
      on the research community, and describes some new additions and potential
      benefits the resource center might have for the ever-changing research interests
      of investigators.

PMID- 22140586
TI  - Economical value of vaccines for the developing countries--the case of Instituto
      Butantan, a public institution in Brazil.

PMID- 22140587
TI  - Laboratory-acquired dengue virus infection--a case report.

PMID- 22140588
TI  - Entamoeba lysyl-tRNA synthetase contains a cytokine-like domain with chemokine
      activity towards human endothelial cells.
AB  - Immunological pressure encountered by protozoan parasites drives the selection of
      strategies to modulate or avoid the immune responses of their hosts. Here we show
      that the parasite Entamoeba histolytica has evolved a chemokine that mimics the
      sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens
      endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like
      polypeptide (EELP) is translated as a domain attached to two different aminoacyl
      tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to
      inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of
      the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to
      generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human
      cells, but its cell specificity is different from that of HsEMAPII. We show that
      cell specificity differences between HsEMAPII and EELP can be swapped by site
      directed mutagenesis of only two residues in the cytokines' signal sequence.
      Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human
      cytokine with modified cell specificity.

PMID- 22140589
TI  - Visceral leishmaniasis in the Indian subcontinent: modelling epidemiology and
      control.
AB  - BACKGROUND: In the Indian subcontinent, about 200 million people are at risk of
      developing visceral leishmaniasis (VL). In 2005, the governments of India, Nepal
      and Bangladesh started the first regional VL elimination program with the aim to
      reduce the annual incidence to less than 1 per 10,000 by 2015. A mathematical
      model was developed to support this elimination program with basic
      quantifications of transmission, disease and intervention parameters. This model
      was used to predict the effects of different intervention strategies. METHODS AND
      FINDINGS: Parameters on the natural history of Leishmania infection were
      estimated based on a literature review and expert opinion or drawn from a
      community intervention trial (the KALANET project). The transmission dynamic of
      Leishmania donovani is rather slow, mainly due to its long incubation period and
      the potentially long persistence of parasites in infected humans. Cellular
      immunity as measured by the Leishmanin skin test (LST) lasts on average for
      roughly one year, and re-infection occurs in intervals of about two years, with
      variation not specified. The model suggests that transmission of L. donovani is
      predominantly maintained by asymptomatically infected hosts. Only patients with
      symptomatic disease were eligible for treatment; thus, in contrast to vector
      control, the treatment of cases had almost no effect on the overall intensity of
      transmission. CONCLUSIONS: Treatment of Kala-azar is necessary on the level of
      the individual patient but may have little effect on transmission of parasites.
      In contrast, vector control or exposure prophylaxis has the potential to
      efficiently reduce transmission of parasites. Based on these findings, control of
      VL should pay more attention to vector-related interventions. Cases of PKDL may
      appear after years and may initiate a new outbreak of disease; interventions
      should therefore be long enough, combined with an active case detection and
      include effective treatment.

PMID- 22140590
TI  - Combining climatic projections and dispersal ability: a method for estimating the
      responses of sandfly vector species to climate change.
AB  - BACKGROUND: In the Old World, sandfly species of the genus Phlebotomus are known
      vectors of Leishmania, Bartonella and several viruses. Recent sandfly catches and
      autochthonous cases of leishmaniasis hint on spreading tendencies of the vectors
      towards Central Europe. However, studies addressing potential future distribution
      of sandflies in the light of a changing European climate are missing.
      METHODOLOGY: Here, we modelled bioclimatic envelopes using MaxEnt for five
      species with proven or assumed vector competence for Leishmania infantum, which
      are either predominantly located in (south-) western (Phlebotomus ariasi, P.
      mascittii and P. perniciosus) or south-eastern Europe (P. neglectus and P.
      perfiliewi). The determined bioclimatic envelopes were transferred to two climate
      change scenarios (A1B and B1) for Central Europe (Austria, Germany and
      Switzerland) using data of the regional climate model COSMO-CLM. We detected the
      most likely way of natural dispersal ("least-cost path") for each species and
      hence determined the accessibility of potential future climatically suitable
      habitats by integrating landscape features, projected changes in climatic
      suitability and wind speed. RESULTS AND RELEVANCE: Results indicate that the
      Central European climate will become increasingly suitable especially for those
      vector species with a current south-western focus of distribution. In general,
      the highest suitability of Central Europe is projected for all species in the
      second half of the 21st century, except for P. perfiliewi. Nevertheless, we show
      that sandflies will hardly be able to occupy their climatically suitable habitats
      entirely, due to their limited natural dispersal ability. A northward spread of
      species with south-eastern focus of distribution may be constrained but not
      completely avoided by the Alps. Our results can be used to install specific
      monitoring systems to the projected risk zones of potential sandfly
      establishment. This is urgently needed for adaptation and coping strategies
      against the emerging spread of sandfly-borne diseases.

PMID- 22140593
TI  - Neglected tropical diseases and the 2012 US presidential election.

PMID- 22140591
TI  - Inhibition of dengue virus entry and multiplication into monocytes using RNA
      interference.
AB  - BACKGROUND: Dengue infection ranks as one of the most significant viral diseases
      of the globe. Currently, there is no specific vaccine or antiviral therapy for
      prevention or treatment. Monocytes/macrophages are the principal target cells for
      dengue virus and are responsible for disseminating the virus after its
      transmission. Dengue virus enters target cells via receptor-mediated endocytosis
      after the viral envelope protein E attaches to the cell surface receptor. This
      study aimed to investigate the effect of silencing the CD-14 associated molecule
      and clathrin-mediated endocytosis using siRNA on dengue virus entry into
      monocytes. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression analysis showed a
      significant down-regulation of the target genes (82.7%, 84.9 and 76.3% for CD-14
      associated molecule, CLTC and DNM2 respectively) in transfected monocytes. The
      effect of silencing of target genes on dengue virus entry into monocytes was
      investigated by infecting silenced and non-silenced monocytes with DENV-2.
      Results showed a significant reduction of infected cells (85.2%), intracellular
      viral RNA load (73.0%), and extracellular viral RNA load (63.0%) in silenced
      monocytes as compared to non-silenced monocytes. CONCLUSIONS/SIGNIFICANCE:
      Silencing the cell surface receptor and clathrin mediated endocytosis using RNA
      interference resulted in inhibition of the dengue virus entry and subsequently
      multiplication of the virus in the monocytes. This might serve as a novel
      promising therapeutic target to attenuate dengue infection and thus reduce
      transmission as well as progression to severe dengue hemorrhagic fever.

PMID- 22140594
TI  - eConsultation in Plastic and Reconstructive Surgery.
AB  - OBJECTIVE: Early studies of plastic surgery patient triage using telemedicine are
      descriptive and deal with feasibility rather than accuracy. The inpatient study
      arm compares on-site wound-evaluation accuracy with remotely viewed digital
      images. The outpatient arm prospectively compares on-site and remote diagnosis,
      management, and outcomes in a busy, urban, reconstructive-surgery clinic. The
      concurrent 6 patient case studies illustrate significant systems improvement by
      using remote consultation. METHODS: A total of 43 inpatients and 100 consecutive
      outpatients were evaluated by on-site and remote surgeons as performed in
      previous arms with digital-camera and store and forward technology. Consent was
      obtained from all patients participating. Agreements regarding diagnosis (skin
      lesion, hand injury, wound type, and scar character) and management (healing
      problem, emergent evaluation, antibiotics, and hospitalization) were calculated.
      RESULTS: In the first study arm, on-site and remote agreement (46%-86% for wound
      description and 65%-81% for management) generally matched agreement among on-site
      surgeons (68%-100% and 84%-89%). Moreover, when on-site agreement was low (68%
      for edema), agreement between on-site and remote surgeons was also low (57%).
      Remote evaluation was least sensitive detecting wound drainage (46%). On-site
      surgeons opted for more treatment, often prescribing antibiotics and admitting
      the patient. The second teleconsult arm provides further evidence of accuracy,
      overall agreement of 32%, sensitivity 48.55%, specificity 96.92%, positive
      predictive value 49.26%, negative predictive value 96.83%, and P < .001 regarding
      diagnosis (skin lesion, hand injury, wound type, wound problem, and scar
      character). Patient transfer, postoperative monitoring, and outcomes via
      electronic image transfer, as well as cost-benefit analysis of this clinic-based
      study, are presented. CONCLUSIONS: eConsultation renders similar outcomes to
      standard, on-site examination in a selected group of plastic surgery patients.
      Remote evaluation may assist triage decisions, thereby decreasing emergency room
      throughput time and office-visit frequency, supplementing satellite facility
      consultation by plastic surgeons, and providing real-time postoperative
      assessments, thereby improving quality and reducing costs.

PMID- 22140592
TI  - Targeting the Wolbachia cell division protein FtsZ as a new approach for
      antifilarial therapy.
AB  - The use of antibiotics targeting the obligate bacterial endosymbiont Wolbachia of
      filarial parasites has been validated as an approach for controlling filarial
      infection in animals and humans. Availability of genomic sequences for the
      Wolbachia (wBm) present in the human filarial parasite Brugia malayi has enabled
      genome-wide searching for new potential drug targets. In the present study, we
      investigated the cell division machinery of wBm and determined that it possesses
      the essential cell division gene ftsZ which was expressed in all developmental
      stages of B. malayi examined. FtsZ is a GTPase thereby making the protein an
      attractive Wolbachia drug target. We described the molecular characterization and
      catalytic properties of Wolbachia FtsZ. We also demonstrated that the GTPase
      activity was inhibited by the natural product, berberine, and small molecule
      inhibitors identified from a high-throughput screen. Furthermore, berberine was
      also effective in reducing motility and reproduction in B. malayi parasites in
      vitro. Our results should facilitate the discovery of selective inhibitors of
      FtsZ as a novel anti-symbiotic approach for controlling filarial infection. 
      NOTE: The nucleotide sequences reported in this paper are available in GenBankTM
      Data Bank under the accession number wAlB-FtsZ (JN616286).

PMID- 22140595
TI  - Post-transcriptional regulation of PDGFalpha-receptor in O-2A progenitor cells.
AB  - latelet-derived growth factor alpha-receptor (PDGFalphaR) mediated signaling
      plays a key role in the development of glial cells of the central nervous system.
      In vivo and in vitro studies show that PDGFalphaR is actively expressed in
      proliferative and motile oligodendrocyte type-2 astrocyte (O-2A) glial progenitor
      cells. However, PDGFalphaR expression is barely detectable in mature glial cells.
      The exact mechanism underlying the loss of PDGFalphaR expression is unknown. In
      this study, we employed a rat brain-derived O-2A glial progenitor cell line, CG4
      as a culture model to investigate signals capable of inhibiting PDGFalphaR gene
      expression. PDGFalphaR mRNA levels decreased significantly as CG4 cells
      differentiated into both oligodendrocyte and astrocyte lineages. We showed that
      inhibition of PDGFalphaR expression was promoted by prostaglandin E2 via protein
      kinase A activation. Both cAMP analogs (db-cAMP and 8'bromo-cAMP) and adenylate
      cyclase activator (forskolin) were potent suppressors of PDGFalphaR expression in
      CG4 cells. This inhibitory effect resulted from an increased destabilization of
      PDGFalphaR mRNA instead of a decreased PDGFalphaR gene transcription.
      Importantly, db-cAMP failed to reduce PDGFalphaR mRNA levels in several
      PDGFalphaR over-expressing human glioma cell lines. Together, these results
      suggest that cAMP-dependent pathway played a key regulatory role in controlling
      PDGFalphaR mRNA levels during normal glial development, and that a breakdown in
      the cross talk between cAMP and PDGF pathways may underlie the uncontrolled
      proliferation and immature differentiation state in the glial tumors.

PMID- 22140596
TI  - Altered gene expression in the spleen of adolescent rats following high ethanol
      concentration binge drinking.
AB  - Binge drinking of alcoholic beverages among adolescents is a common practice that
      can have serious health consequences. Alcohol is a potent immunomodulator that
      alters a wide range of immune responses. However, it is unclear whether there is
      a differential immune response to alcoholic beverages with a high versus low
      concentration of ethanol. In this study, we used a PCR array containing 46 primer
      pairs of selected genes to compare mRNA expression in the spleen, an immune
      system organ, of adolescent rats following binge drinking of alcohol solutions
      containing either 20% or 52% ethanol (v/v, 4.8 g/kg daily dosage), or water
      (control) for 3 d. We found that, expression of IL-1beta, IL-6, CCL2, and GABA(A)
      receptor alpha2 subunit in the spleen were decreased, and mGluR5 and 5-HT3A
      receptor expression were increased after administration of an ethanol solution
      containing 52% ethanol, but not one with 20% ethanol. Our data suggest that
      alcohol-mediated immunomodulatory effects are, in part, dependent on the ethanol
      by volume concentration. This is the first study to show that exposure to a high
      ethanol percentage beverage can have more profound effects on immune responses
      than one with a low percentage of ethanol.

PMID- 22140597
TI  - Reference values for echocardiographic parameters and indexes of left ventricular
      function in healthy, young adult sheep used in translational research: comparison
      with standardized values in humans.
AB  - Ovine models of ischemic heart disease and cardiac failure are increasingly used
      in translational research. However, reliable extrapolation of the results to the
      clinical setting requires knowing if ovine normal left ventricular (LV) function
      is comparable to that of humans. We thus assessed for echocardiographic LV
      dimensions and indexes in a large normal adult sheep population and compared them
      with standardized values in normal human adults. Bidimensional and tissue Doppler
      echocardiograms were performed in 69 young adult Corriedale sheep under light
      sedation. LV dimensions and indexes of systolic and diastolic function were
      measured. Absolute and body surface areanormalized values were compared to those
      for normal adult humans and their statistical distribution was assessed.
      Normalized dimensions (except for end diastolic diameter) as well as ejection
      fraction and fractional shortening fell within the ranges established by the
      American Society of Echocardiography and European Association of Echocardiography
      for normal adult humans. Normalized end diastolic diameter exceeded the upper
      normal limit but got close to it when correcting for the higher heart mass/body
      surface area ratio of sheep with respect to humans. Diastolic parameters also
      fell within normal human ranges except for a slightly lower mitral deceleration
      time. All values exhibited a Gaussian distribution. We conclude that
      echocardiographic parameters of systolic and diastolic LV performance in young
      adult sheep can be reliably extrapolated to the adult human, thus supporting the
      use of ovine models of human heart disease in translational research.

PMID- 22140598
TI  - Membrane type-1 matrix metalloproteinase (MT1-MMP) correlates with the expression
      and activation of matrix metalloproteinase-2 (MMP-2) in inflammatory breast
      cancer.
AB  - Inflammatory breast cancer (IBC) represents the most aggressive form of breast
      cancer, characterized by rapid progression, involvement of dermal lymphatic
      emboli and extensive metastatic lymph nodes. Matrix metalloproteinases (MMPs) are
      proteolytic enzymes that play an important role in cancer invasion and
      metastasis. Although the role of MMPs in non-IBC is well studied, little is known
      about its role in IBC. Thus the goal of the present study was to 1) investigate
      the expression and activity levels of membrane type matrix metalloproteinase-1
      (MT1-MMP) and matrix metalloproteinase-2 and-9 (MMP-2 and MMP-9) in IBC versus
      non-IBC tissue samples and; 2) test correlation between expression of MT1-MMP and
      pro- and active forms of MMP-2 and MMP-9. We enrolled 51 breast cancer patients,
      21 were diagnosed as IBC and 30 as non-IBC. Level of expression of MT1-MMP in
      carcinoma tissue was assessed by immunoblot and immunohistochemistry techniques.
      The expression and activation of MMP-2 and MMP-9 was measured by gelatin
      zymography. Our results revealed that MT1-MMP, pro-MMP-2, pro-MMP-9 and active
      MMP-2 were more expressed in IBC tissue versus non-IBC. Furthermore, we found
      that MT1-MMP expression correlates with expression of pro-MMP-2, pro-MMP-9 and
      active MMP-2 in IBC tissue samples and with MMP-9 in non-IBC tissue sample. In
      conclusion, our study suggests a role of MT1-MMP in inflammatory breast cancer
      disease progression.

PMID- 22140599
TI  - Hypertonic/hyperoncotic solution attenuate blood-brain barrier breakdown and
      brain pathology in whole body hyperthermia rats.
AB  - This study was designed to investigate the effects of hypertonic/hyperoncotic
      solution on blood-brain barrier damage, brain edema and morphological changes of
      rats during whole body hyperthermia. 90 adult male Sprague-Dawley rats were
      randomized into 5 groups: Control group (a room temperature for 4 hours); Whole
      body hyperthermia group without solution treatment; Whole body hyperthermia group
      with Ringer's solution treatment; Whole body hyperthermia group with hydroxyethyl
      starch and Ringer's solution treatment; Whole body hyperthermia group with
      Hypertonic/hyperoncotic solution treatment. All rats except those of control
      group were housed in a heated container and maintained at 36 degrees C for 3
      hours until the rectal temperature reached 41-42 degrees C. Corresponding
      solutions were administered intravenously at the beginning of whole body
      hyperthermia within 30 minutes as designed. Following whole body hyperthermia,
      rats were subsequently cooled down for 1h. Evans blue was administered
      intravenously when the rectal temperature was cooled down to 37 degrees C. The
      leakage of Evans blue-albumin and water content of brain were calculated and
      morphological changes were investigated. In group with hypertonic/hyperoncotic
      solution treatment, brain water content and the leakage of Evans blue-albumin
      were the lowest among the four whole body hyperthermia groups. Compared with the
      other three whole body hyperthermia groups, in which profound to moderate damages
      to blood-brain barrier and brain tissue and cells were found, there were only
      slight morphological changes in the group with hypertonic/hyperoncotic solutionon
      treatment. Treatment with hypertonic/hyperoncotic solution appeared to attenuate
      the injury to blood-brain barrier and reduce brain edema and cell morphological
      changes in whole body hyperthermia rats.

PMID- 22140600
TI  - Pathogenetic mechanisms of posttraumatic osteoarthritis: opportunities for early
      intervention.
AB  - Osteoarthritis (OA) is characterized by joint pain and stiffness with
      radiographic evidence of joint space narrowing, osteophytes, and subchondral bone
      sclerosis. Posttraumatic OA (PTOA) arises from joint trauma, which accounts for a
      fraction of all patients with OA. Articular cartilage breakdown can occur soon or
      for years after a joint injury. Even with the current care of joint injuries,
      such as anatomic reduction and rigid fixation of intra-articular fractures and
      reconstruction of ruptured ligaments with successful restoration of joint
      biomechanics, the risk of PTOA after joint injuries ranges from 20% to more than
      50%. The time course for the progression of PTOA is highly variable and risk of
      PTOA increases with patient age at the time of joint injury, suggesting that
      biologic factors may be involved in the progression of PTOA. Therapeutic options
      are limited due largely to the lack of information on the mechanisms underlying
      the progression of PTOA. This review summarizes the current studies on the
      pathogenetic mechanisms of PTOA, with a main focus on the metabolic changes in
      articular cartilage in the acute posttraumatic phase and the early chronic phase,
      a clinically asymptomatic period. Recent studies have revealed that mechanical
      damage to the articular tissues may lead to changes in gene expression and
      cartilage metabolism, which could trigger a cascade of events leading to
      degradation of articular cartilage and pathologic changes in other joint tissues.
      Understanding the mechanobiologic, molecular and cellular changes that lead to
      continued cartilage degradation in the relatively early phases after joint injury
      may open up new opportunities for early clinical intervention.

PMID- 22140601
TI  - Differentiated intestinal epithelial cells express high levels of TGF-beta
      receptors and exhibit increased sensitivity to growth inhibition.
AB  - BACKGROUND: Intestinal epithelial cells (IECs) within crypts continuously divide
      and differentiate as they migrate up towards the luminal surface of the mucosa.
      With the onset of differentiation, IECs lose their proliferative potential, but
      the exact mechanism remains unknown. This current study examined the involvement
      of the TGF-beta signaling pathway in this process. METHODS: Studies were
      conducted in the IEC-6 cell line derived from rat small intestinal crypt cells.
      Cell differentiation was induced by forced expression of the Cdx2 gene, a
      transcription factor responsible for controlling intestinal epithelial cell
      differentiation. RESULTS: Forced expression of the Cdx2 gene in stable Cdx2
      transfected IEC-6 cells resulted in a differentiated phenotype as indicated by
      morphological features and increased expression of sucrase-isomaltase. Levels of
      TGF-beta type I receptor (TGFbeta-RI) and TGF-beta type II receptor (TGFbeta-RII)
      increased in these differentiated epithelial cells. The induced TGFbeta-RI and
      TGFbeta-RII expression in Cdx2-transfected IEC-6 cells was associated with
      increased sensitivity to TGF-beta-induced growth inhibition. Depletion of
      cellular polyamines further increased TGF-beta receptor expression and
      additionally enhanced the response to TGF-beta-induced growth inhibition.
      Increased TGFbeta-RI and RII in polyamine-deficient cells were also associated
      with an induction in JunD/AP-1 activity. CONCLUSIONS: These results indicate that
      the loss of the proliferative potential in differentiated IECs results partially
      from the increased expression of TGF-beta receptors.

PMID- 22140602
TI  - An old herbal medicine with a potentially new therapeutic application in
      inflammatory bowel disease.
AB  - Inflammatory Bowel Disease (IBD) is a chronic and frequently disabling
      inflammatory disorder of the intestine. New developments in IBD therapy are
      primarily focused on biologic treatments; however, they are both expensive and
      associated with significant side effects. Here, we provide the first preclinical
      evidence that YunNan BaiYao (YNBY), a well-known traditional Chinese herbal
      remedy frequently used for treating hemorrhages and wounds, can effectively
      alleviate experimental colitis. Oral administration of YNBY in drinking water
      significantly reduced the disease activities of both DSS- and TNBS-induced
      experimental colitis. Mechanistic studies revealed that the effectiveness of YNBY
      was not due to an anti-bacterial function since YNBY had no effect on E. coli
      growth. Rather, it exhibited an anti-inflammatory or immunosuppressive function:
      In the DSS colitis model, YNBY treatment decreased the levels of several pro
      inflammatory cytokines in colonic mucosa, including TNFalpha, IL-12p40, and IL
      17. Similar cytokine changes were also observed in mouse serum, suggesting that
      systemic changes in general reflect the changes in the affected colon.
      Significant down-regulation of IL-12p40 and IL-17, in addition to IFNgamma, was
      also seen in TNBS-colitis model. Another potential mechanism for the anti
      inflammatory effects of YNBY involves the selective suppression of pro
      inflammatory immune cells: YNBY effectively suppressed the growth of multiple T-
      and B-lymphocytes, including Molt-4, Jurkat, and EBV-transformed human B
      lymphocytes, more potently than 6-mecaptopurine (6-MP) and 5-aminosalicylic acid
      (5-ASA), two of the most commonly used first-line drugs in IBD therapy. In sharp
      contrast, YNBY exhibited no cytotoxicity to colonic epithelial cells (Caco-2
      cells), even at the concentration 10-fold higher than that used in the lymphocyte
      model; and instead promoted cell spreading and wound healing. These results
      strongly suggest that YNBY not only has effective anti-inflammatory properties
      through suppressing lymphocyte growth and pro-inflammatory cytokine expression,
      but also can promote intestinal epithelial wound-healing and repair. Therefore,
      YNBY demonstrates strong potential as an alternative herbal therapy for IBD.

PMID- 22140604
TI  - HDFx: a novel biologic immunomodulator is therapeutically -effective in
      hemorrhagic and intestinal-ischemic shock: importance of microcirculatory
      immunological interactions and their potential implications for the warfighter
      and disaster victims.
AB  - Recently, we have reported on the discovery of a new, conserved protein (35-40
      kD), termed HDFx, that protects rats, guinea-pigs, mice and rabbits against
      lethal hemorrhage, endotoxins, and traumatic injury when given, systemically, as
      a pretreatment. HDFx was also found to stimulate several arms of the immune
      system. The present report demonstrates, for the first time, that HDFx ,when
      administered post-hemorrhage and post-intestinal ischemia shock -trauma, yields
      increased survival rates, elevates falling arterial blood pressures, possesses
      unique actions in the microvasculature, stimulates depressed RES phagocytosis
      (normally observed in animals and humans during blood loss, sepsis and trauma),
      and preserves cytokine levels in lymphocytes obtained from animals subjected to
      hemorrhage and traumatic shock. We believe that HDFx presents a potential brand
      new therapeutic approach:1)for the injured warfighter on the battlefield, 2)for
      victims of major disasters, 3)as an adjunct for patients undergoing high -risk
      surgical procedures commonly found in open-heart surgery, cancers, and in
      neurosurgeries. Use of HDFx could potentially allow oncologists to decrease
      chemotherapy dosing, while increasing patient survival chances.

PMID- 22140603
TI  - Role of myeloid-specific G-protein coupled receptor kinase-2 in sepsis.
AB  - Previous studies have implicated a critical role for G-protein coupled receptor
      kinase-2 (GRK2) in sepsis owing to its ability to regulate inflammatory response
      and chemotaxis of immune cells. We therefore, hypothesized that deletion of GRK2
      in myeloid cells would significantly modulate the pathogenesis of polymicrobial
      sepsis. To test this hypothesis, we induced cecal ligation and puncture (CLP), in
      mice with myeloid-specific deletion of GRK2 and the corresponding GRK2 wild type
      littermates and determined the inflammatory response (IL-6 and IL-10), immune
      cell infiltration, bacterial load and survival. Six hours after surgery, plasma
      IL-6 and IL-6:IL-10 ratios were significantly enhanced in the GRK2 knockouts
      compared to the GRK2 wild type mice. Compared to these effects, IL-6was
      significantly elevated in the bronchoalveolar lavage but not in the peritoneal
      fluid of the GRK2 knockout mice. On the other hand, peritoneal IL-10 was
      significantly elevated in the GRK2 knockout mice compared to the GRK2 wild type.
      Even though GRK2 knockout mice exhibited an exaggerated cytokine response, there
      was no difference in immune cell infiltration into the primary site of infection
      or in bacterial clearance when compared between the GRK2 wild type and GRK2
      knockout mice after surgery. Furthermore, in spite of the enhanced pro
      inflammatory profile early after surgery, there was only a modest increase in
      mortality in the GRK2 knockout compared to the GRK2 wild type mice after CLP.
      Together, our studies demonstrate that myeloid-specific knockout of GRK2 renders
      the mice more susceptible to an early pro-inflammatory state. However, myeloid
      specific GRK2 is not involved in immune cell infiltration to the primary site of
      infection or in bacterial clearance and does not significantly modulate mortality
      in the cecal ligation puncture model of polymicrobial sepsis.

PMID- 22140605
TI  - The Moderating Effects of Mother-Adolescent Relations on the Longitudinal
      Association between Father and Offspring Depressive Symptoms.
AB  - Little theoretical or empirical attention has been given to factors associated
      with better or worse outcomes in offspring of depressed fathers. Drawing from
      interpersonal models of intergenerational depression transmission in children of
      depressed mothers, the present investigation of adolescents and their families (N
      = 424) examined maternal warmth and hostility as moderators of the longitudinal
      association between paternal and adolescent depressive symptoms. Controlling for
      family demographic variables, previous adolescent depressive symptoms, and
      maternal depressive symptoms, fathers' depressive symptoms predicted offspring
      depressive symptoms among adolescents experiencing low maternal warmth or high
      maternal hostility. Adolescent girls reporting adversity in their relationships
      with their mothers were the most vulnerable to risk associated with paternal
      depressive symptoms. These findings highlight the implications of fathers' mental
      health for adolescent psychological well-being and add to the growing evidence
      that family relationships play a crucial role in the transmission of depression
      from one generation to the next.

PMID- 22140606
TI  - Mechanisms Mediating the Synergistic Anticancer Effects of Combined gamma
      Tocotrienol and Celecoxib Treatment.
AB  - AIM: To characterize the intracellular signaling mechanisms mediating the
      synergistic anticancer effects of combined gamma-tocotrienol and celecoxib
      treatment in neoplastic +SA mouse mammary epithelial cells in vitro.  METHODS:
      +SA mammary tumor cells in different treatment groups were maintained in serum
      free defined media containing 10ng/ml EGF as a mitogen and exposed to various
      doses of gamma-tocotrienol and celecoxib alone or in combination. After a 96 hr
      culture period, cells were collected and whole cell lysates were subjected to
      Western blot analysis to determine treatment effects on intracellular signaling
      proteins associated with EGF-dependent mitogenesis and survival, and
      prostaglandin synthesis and responsiveness.  RESULTS: Treatment with high doses
      of gamma-tocotrienol or celecoxib alone inhibited Akt activation and downstream
      signaling and NFkappaB activation. Similar treatment with gamma-tocotrienol also
      decreased concentration and activation of ErbB2-4 receptors, whereas celecoxib
      only inhibited ErbB2-4 receptor activation. In contrast, combined treatment with
      subeffective doses of gamma-tocotrienol and celecoxib resulted in a large
      decrease ErbB2-4 receptor levels and activation, a decrease in PGE(2) levels, and
      a corresponding increase in prostaglandin EP2 and EP4 receptor levels. Combined
      treatment also induced an increase in the prostaglandin catabolizing enzyme,
      PGDH.  CONCLUSION: The synergistic anticancer effects of combined low dose gamma
      tocotrienol and celecoxib treatment in +SA mammary tumor cells are mediated by
      COX-2-dependent mechanisms associated with a suppression in PGE(2) levels, as
      well as, COX-2-independent mechanisms associated with a reduction in ErbB2-4
      receptor levels, activation, and subsequent reduction in downstream Akt and
      NFkappaB mitogenic signaling.

PMID- 22140608
TI  - Development of an Antiviral Screening Protocol: One-Stone-Two-Birds.
AB  - As prophylactic therapies and vaccines against viral infections continue to
      improve, drug resistant strains are continuing to arise; therefore it is
      imperative to develop new therapeutics against these diseases. For highly
      pathogenic viruses, such as Ebola and H5N1 influenza virus, the need for
      antivirals is even more urgent due to limited therapeutics against these viruses.
      Furthermore, the high pathogenicity of such viruses often makes it difficult to
      work with such agents. In this report, we describe a protocol called "One-stone
      two-birds" which provides a safe and efficient screening system to identify anti
      flu (entry) and anti-HIV (replication) activities. Using plant extracts as an
      example, we demonstrate the utility of this protocol in antiviral screening.

PMID- 22140609
TI  - Increased length of inpatient stay and poor clinical coding: audit of patients
      with diabetes.
AB  - OBJECTIVES: People with diabetes stay in hospital for longer than those without
      diabetes for similar conditions. Clinical coding is poor across all specialties.
      Inpatients with diabetes often have unrecognized foot problems. We wanted to look
      at the relationships between these factors. DESIGN: A single day audit, looking
      at the prevalence of diabetes in all adult inpatients. Also looking at their feet
      to find out how many were high-risk or had existing problems. SETTING: A 998-bed
      university teaching hospital. PARTICIPANTS: All adult inpatients. MAIN OUTCOME
      MEASURES: (a) To see if patients with diabetes and foot problems were in hospital
      for longer than the national average length of stay compared with national data;
      (b) to see if there were people in hospital with acute foot problems who were not
      known to the specialist diabetic foot team; and (c) to assess the accuracy of
      clinical coding. RESULTS: We identified 110 people with diabetes. However,
      discharge coding data for inpatients on that day showed 119 people with diabetes.
      Length of stay (LOS) was substantially higher for those with diabetes compared to
      those without (+/- SD) at 22.39 (22.26) days, vs. 11.68 (6.46) (P < 0.001).
      Finally, clinical coding was poor with some people who had been identified as
      having diabetes on the audit, who were not coded as such on discharge.
      CONCLUSION: Clinical coding - which is dependent on discharge summaries - poorly
      reflects diagnoses. Additionally, length of stay is significantly longer than
      previous estimates. The discrepancy between coding and diagnosis needs addressing
      by increasing the levels of awareness and education of coders and physicians. We
      suggest that our data be used by healthcare planners when deciding on future
      tariffs.

PMID- 22140610
TI  - XMPMA: acute on chronic ventilatory failure managed successfully with non
      invasive ventilation.

PMID- 22140607
TI  - Nicotinamide Phosphoribosyltransferase in Human Diseases.
AB  - Nicotinamide phosphoribosyltransferase (NAMPT) was first reported as a pre-B-cell
      colony enhancing factor in 1994 with little notice, but it has received
      increasing attention in recent years due to accumulating evidence indicating that
      NAMPT is a pleiotropic protein such as a growth factor, a cytokine, an enzyme and
      a visfatin. Now, NAMPT has been accepted as an official name of this protein.
      Because of NAMPT's multiple functions in a variety of physiological processes,
      their dysregulations have been implicated in the pathogenesis of a number of
      human diseases or conditions such as acute lung injury, aging, atherosclerosis,
      cancer, diabetes, rheumatoid arthritis and sepsis. This review will cover the
      current understanding of NAMPT's structure and functions with an emphasis on
      recent progress of nicotinamide phosphoribosyltransferase's pathological roles in
      various human diseases and conditions. Future directions on exploring its Terra
      incognita will be offered in the end.

PMID- 22140611
TI  - Unrecognized pseudohyperkalaemia in essential thrombocythaemia.

PMID- 22140612
TI  - An unsual case of persistent inguinal swelling - beware immunodeficiency.

PMID- 22140613
TI  - Weight versus volume in breast surgery: an observational study.
AB  - OBJECTIVES: The study hypothesis is to assess correlation of breast specimen
      weight versus volume. DESIGN: Consecutive patients undergoing breast surgery at a
      single tertiary referral centre during a 6-month period were included. Specimen
      weight was measured in grams. Direct volume measurements were performed using
      water displacement. Data including side of the breast, age and menstrual status
      of the patient were noted. SETTING: Knowledge of breast volume provides an
      objective guide in facilitating the achievements of balance in reconstructive
      operations. Surgeons use intraoperative weight measurements from individual
      breasts to calculate the breast volume assuming that weight is equal to the
      volume of the specimen. However, it is unclear whether weight accurately reveals
      the true volume of resection. PARTICIPANTS: Forty-one patients were included in
      the study with 28 having bilateral surgeries, 13 having unilateral procedures
      giving a total of 69 breast specimens. MAIN OUTCOME MEASURES: Breast specimen
      weight correlation to breast specimen volume. RESULTS: The mean age of the group
      was 42.4 years. Fifty-two specimens were from premenopausal patients and 17 were
      of postmenopausal. Thirty-five were left-sided. Twenty-six patients had bilateral
      breast reduction, two had bilateral mastectomy, nine had a unilateral mastectomy
      and four patients had a unilateral breast reduction. The difference between
      weight and volume of these breasts was 36.4 units (6.6% difference). The
      difference in measurement of weight and volume in premenopausal was 37.6 units
      compared to 32.6 units in postmenopausal women. The density was 1.07 and 1.06,
      respectively. This was statistically not significant. CONCLUSIONS: No significant
      difference between volume and weight was seen in this series. Furthermore, we are
      unable to support the notion that premenopausal patients have a significant
      difference in the proportion of fatty and glandular tissue as there was little
      difference between the weight and the volume. An easy, clinically proper formula
      for the quantification of actual breast volume has yet to be derived.

PMID- 22140614
TI  - Pneumatosis intestinalis and hepatic portal venous gas on computed tomography - a
      non-lethal outcome.

PMID- 22140615
TI  - Juxtapapillary duodenal diverticulum masquerading as a cystic pancreatic
      neoplasm.

PMID- 22140616
TI  - Extensive pyogenic myositis of the hip in an immuno-competent patient.

PMID- 22140617
TI  - Elective and emergency cervical cerclage and immediate pregnancy outcomes: a
      retrospective observational study.
AB  - OBJECTIVES: To look retrospectively at patients undergoing elective, ultrasound
      indicated and rescue cervical cerclage, examine the immediate pregnancy outcomes
      and compare them. DESIGN: This was a retrospective observational study using the
      maternity and neonatal databank to identify patients having cervical cerclage
      between 1985 and 2009 inclusive. Data extracted included patient demographics,
      gestation of suture insertion, gestation at delivery, mode of delivery and
      initial pregnancy outcome. Further information on selected patients having
      cerclages over 16 weeks gestation was collected from case-notes. SETTING:
      Aberdeen Maternity Hospital, North East Scotland. PARTICIPANTS: All patients
      having cervical cerclage between 1985 and 2009. MAIN OUTCOME MEASURES: Gestation
      at delivery, live birth rate and birth weight. RESULTS: A total of 177 sutures
      were inserted - 116 electively and 61 as an emergency procedure. Time trends of
      cervical cerclage revealed a bimodal distribution and in the last four years
      there has been a general increase in the number of emergency sutures while the
      number of elective cerclages has remained relatively constant. There was little
      difference in the gestation at delivery between the elective and emergency
      cerclage groups (35 and 33 weeks, respectively), live birth rate (93% and 92%,
      respectively) and the difference in mean birth weight did not reach statistical
      significance. Case-notes were obtained for 25 patients undergoing ultrasound
      indicated cerclage and nine patients undergoing rescue cerclage. There was a
      higher suture associated complication rate in the rescue cerclage group (33% vs.
      12% in the ultrasound indicated cerclage group) and the mean gestation of
      delivery was lower (26 weeks vs. 32 weeks). The birth weight was significantly
      lower and the neonatal death rate higher in the rescue cerclage group.
      CONCLUSIONS: Elective and ultrasound indicated cervical cerclage appear to have
      low complication rates and high live birth rates. Rescue cerclage has a high
      complication rate and is therefore associated with poor outcome.

PMID- 22140618
TI  - Primary meningioma of the middle ear.

PMID- 22140619
TI  - The world of pulmonary vascular disease.

PMID- 22140620
TI  - The genetics of pulmonary arterial hypertension in the post-BMPR2 era.
AB  - Pulmonary arterial hypertension (PAH) is a rapidly progressive and fatal disease
      for which there is an ever-expanding body of genetic and related
      pathophysiological information on disease pathogenesis. The most common single
      culprit gene known is BMPR2, and animal models of the disease in several forms
      exist. There is a wealth of genetic data regarding modifiers of disease
      expression, penetrance, and severity. Despite the rapid accumulation of data in
      the last decade, a complete picture of the molecular pathogenesis of PAH leading
      to novel therapies is lacking. In this review, we attempt to summarize the
      current understanding of PAH from the genetic perspective. The most recent PAH
      demographics are discussed. Heritable PAH in the post-BMPR2 era is examined in
      detail as the most robust model of PAH genetics in both animal models and human
      pedigrees. Important downstream molecular pathways and modifiers of disease
      expression are reviewed in light of what is known about PAH pathogenesis. Current
      and emerging therapies are examined in light of genetic data. The role of genetic
      testing in PAH in the post-BMPR2 era is discussed. Finally, directions for future
      investigations that ideally will fulfill the promise of novel therapeutic or
      preventive strategies are discussed.

PMID- 22140621
TI  - COPD/emphysema: The vascular story.
AB  - In this perspective, we review published data which support the concept that many
      or most chronic and progressive lung diseases also involve the lung vessels and
      that microvascular abnormalities and endothelial cell death contribute to the
      pathobiology of emphysema. Lung vessel maintenance depends on Vascular
      Endothelial Growth Factor signaling and both are compromised in the emphysematous
      lung tissue. Although hypoxic pulmonary vasoconstriction has been considered as
      an important factor contributing to the vascular remodeling in chronic
      obstructive pulmonary disease (COPD) (COPD/emphysema, it is now clear that
      inhaled cigarette smoke can damage the lung vessels independent of the lung
      vascular tone. We propose that a "sick lung circulation" rather than the right
      heart afterload may better explain the cardiac abnormalities in COPD patients
      which are usually summarized with the term "cor pulmonale." The mechanisms and
      causes of pulmonary hypertension are likely complex and include vessel loss, in
      situ thrombosis, and endothelial cell dysfunction. Assessment of the functional
      importance of pulmonary hypertension in COPD requires hemodynamic measurements
      during exercise.

PMID- 22140622
TI  - Surgical treatment of pulmonary hypertension: Lung transplantation.
AB  - Pulmonary hypertension (PH) is a serious and progressive disorder that results in
      right ventricular dysfunction that lead to subsequent right heart failure and
      death. When untreated the median survival for these patients is 2.8 years. Over
      the past decade advances in disease specific medical therapy considerably changed
      the natural history. This is reflected in a threefold decrease in the number of
      patients undergoing lung transplantation for PH which used to be main stay of
      treatment. Despite the successful development of medical therapy lung transplant
      still remains the gold standard for patients who fail medical therapy. Referral
      for lung transplant is recommended when patients have a less than 2-3 years of
      predicted survival or in NYHA class III or IV. Both single and bilateral lung
      transplants have been successfully performed for PH but outcome analyses and
      survival comparisons generally favor a bilateral lung transplant.

PMID- 22140623
TI  - Apelin and pulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a devastating disease characterized by
      pulmonary vasoconstriction, pulmonary arterial remodeling, abnormal angiogenesis
      and impaired right ventricular function. Despite progress in pharmacological
      therapy, there is still no cure for PAH. The peptide apelin and the G-protein
      coupled apelin receptor (APLNR) are expressed in several tissues throughout the
      organism. Apelin is localized in vascular endothelial cells while the APLNR is
      localized in both endothelial and smooth muscle cells in vessels and in the
      heart. Apelin is regulated by hypoxia inducible factor -1alpha and bone
      morphogenetic protein receptor-2. Patients with PAH have lower levels of plasma
      apelin, and decreased apelin expression in pulmonary endothelial cells. Apelin
      has therefore been proposed as a potential biomarker for PAH. Furthermore, apelin
      plays a role in angiogenesis and regulates endothelial and smooth muscle cell
      apoptosis and proliferation complementary and opposite to vascular endothelial
      growth factor. In the systemic circulation, apelin modulates endothelial nitric
      oxide synthase (eNOS) expression, induces eNOS-dependent vasodilatation,
      counteracts angiotensin-II mediated vasoconstriction, and has positive inotropic
      and cardioprotective effects. Apelin attenuates vasoconstriction in isolated rat
      pulmonary arteries, and chronic treatment with apelin attenuates the development
      of pulmonary hypertension in animal models. The existing literature thus renders
      APLNR an interesting potential new therapeutic target for PH.

PMID- 22140624
TI  - Epigenetic mechanisms of pulmonary hypertension.
AB  - Epigenetics refers to changes in phenotype and gene expression that occur without
      alterations in DNA sequence. Epigenetic modifications of the genome can be
      acquired de novo and are potentially heritable. This review focuses on the
      emerging recognition of a role for epigenetics in the development of pulmonary
      arterial hypertension (PAH). Lessons learned from the epigenetics in cancer and
      neurodevelopmental diseases, such as Prader-Willi syndrome, can be applied to
      PAH. These syndromes suggest that there is substantial genetic and epigenetic
      cross-talk such that a single phenotype can result from a genetic cause, an
      epigenetic cause, or a combined abnormality. There are three major mechanisms of
      epigenetic regulation, including methylation of CpG islands, mediated by DNA
      methyltransferases, modification of histone proteins, and microRNAs. There is
      substantial interaction between these epigenetic mechanisms. Recently, it was
      discovered that there may be an epigenetic component to PAH. In PAH there is
      downregulation of superoxide dismutase 2 (SOD2) and normoxic activation of
      hypoxia inducible factor (HIF-1alpha). This decrease in SOD2 results from
      methylation of CpG islands in SOD2 by lung DNA methyltransferases. The partial
      silencing of SOD2 alters redox signaling, activates HIF-1alpha) and leads to
      excessive cell proliferation. The same hyperproliferative epigenetic abnormality
      occurs in cancer. These epigenetic abnormalities can be therapeutically reversed.
      Epigenetic mechanisms may mediate gene-environment interactions in PAH and
      explain the great variability in susceptibility to stimuli such as anorexigens,
      virus, and shunts. Epigenetics may be relevant to the female predisposition to
      PAH and the incomplete penetrance of BMPR2 mutations in familial PAH.

PMID- 22140626
TI  - Blood flow redistribution and ventilation-perfusion mismatch during embolic
      pulmonary arterial occlusion.
AB  - Acute pulmonary embolism causes redistribution of blood in the lung, which
      impairs ventilation/perfusion matching and gas exchange and can elevate pulmonary
      arterial pressure (PAP) by increasing pulmonary vascular resistance (PVR). An
      anatomically-based multi-scale model of the human pulmonary circulation was used
      to simulate pre- and post-occlusion flow, to study blood flow redistribution in
      the presence of an embolus, and to evaluate whether reduction in perfused
      vascular bed is sufficient to increase PAP to hypertensive levels, or whether
      other vasoconstrictive mechanisms are necessary. A model of oxygen transfer from
      air to blood was included to assess the impact of vascular occlusion on oxygen
      exchange. Emboli of 5, 7, and 10 mm radius were introduced to occlude increasing
      proportions of the vasculature. Blood flow redistribution was calculated after
      arterial occlusion, giving predictions of PAP, PVR, flow redistribution, and
      micro-circulatory flow dynamics. Because of the large flow reserve capacity (via
      both capillary recruitment and distension), approximately 55% of the vasculature
      was occluded before PAP reached clinically significant levels indicative of
      hypertension. In contrast, model predictions showed that even relatively low
      levels of occlusion could cause localized oxygen deficit. Flow preferentially
      redistributed to gravitationally non-dependent regions regardless of occlusion
      location, due to the greater potential for capillary recruitment in this region.
      Red blood cell transit times decreased below the minimum time for oxygen
      saturation (<0.25 s) and capillary pressures became high enough to initiate cell
      damage (which may result in edema) only after ~80% of the lung was occluded.

PMID- 22140625
TI  - MicroRNAs-control of essential genes: Implications for pulmonary vascular
      disease.
AB  - During normal lung development and in lung diseases structural cells in the lungs
      adapt to permit changes in lung function. Fibroblasts, myofibroblasts, smooth
      muscle, epithelial cells, and various progenitor cells can all undergo phenotypic
      modulation. In the pulmonary vasculature occlusive vascular lesions that occur in
      severe pulmonary arterial hypertension are multifocal, polyclonal lesions
      containing cells presumed to have undergone phenotypic transition resulting in
      altered proliferation, cell lifespan or contractility. Dynamic changes in gene
      expression and protein composition that underlie processes responsible for such
      cellular plasticity are not fully defined. Advances in molecular biology have
      shown that multiple classes of ribonucleic acid (RNA) collaborate to establish
      the set of proteins expressed in a cell. Both coding Messenger Ribonucleic acid
      (mRNA) and small noncoding RNAs (miRNA) act via multiple parallel signaling
      pathways to regulate transcription, mRNA processing, mRNA stability, translation
      and possibly protein lifespan. Rapid progress has been made in describing dynamic
      features of miRNA expression and miRNA function in some vascular tissues. However
      posttranscriptional gene silencing by microRNA-mediated mRNA degradation and
      translational blockade is not as well defined in the pulmonary vasculature.
      Recent progress in defining miRNAs that modulate vascular cell phenotypes is
      reviewed to illustrate both functional and therapeutic significance of small
      noncoding RNAs in pulmonary arterial hypertension.

PMID- 22140627
TI  - Pulmonary hemodynamic responses to inhaled NO in chronic heart failure depend on
      PDE5 G(-1142)T polymorphism.
AB  - To evaluate the vasoconstrictor component of PH in CHF by investigating the
      hemodynamic response to inhaled nitric oxide (iNO) and to determine whether this
      response was influenced by the phosphodiesterase 5 gene (PDE5) G(1142)T
      polymorphism. CHF patients underwent right heart catheterization at rest and
      after 20 ppm of iNO and plasma cGMP and PDE5 G(1142)T polymorphism
      determinations. Of the 72 included CHF patients (mean age, 53+/-1 years; mean
      left ventricular ejection fraction, 29+/-1%; and mean pulmonary artery pressure,
      25.5+/-1.3 mmHg), 54% had ischemic heart disease. Proportions of patients with
      the TT, GT, and GG genotypes were 39%, 42% and 19% respectively. Baseline
      hemodynamic characteristics were not significantly different across PDE5 genotype
      groups, although pulmonary capillary wedge pressure (PCWP) tended to be lower in
      the TT group (P=0.09). Baseline plasma cGMP levels were significantly lower in
      the TT than in the GG and GT patients. With iNO, PVR diminished in TT (-33%) but
      not GG (-1.6%) or GT (0%) patients (P=0.002); and PCWP increased more in TT than
      in GT (P<0.05) or GG (P<0.003) patients. The PDE5 G(-1142) polymorphism is
      therefore a major contributor to the iNO-induced PVR decrease in CHF.

PMID- 22140628
TI  - Pharmacogenomics in pulmonary arterial hypertension: Toward a mechanistic, target
      based approach to therapy.
AB  - Pharmacogenomics is the study of how genetic variations influence the response to
      drugs, by correlating gene expression with the drug's efficacy and toxicity. This
      concept has recently been successfully applied in oncology. To test its
      applicability to PAH, we examined two experimental models of the disease: mice
      with deletion of the Vasoactive Intestinal Peptide gene (VIP(- /-)); and rats
      injected with monocrotaline (MCT). Since the two models express comparable
      phenotypic features, we analyzed their particular gene alterations, with special
      reference to genes related to pulmonary vasoconstriction, vascular remodeling,
      and inflammation. We then compared the phenotypic and genotypic responses in each
      model to treatment with the same drug, VIP. In untreated VIP(-/-) mice there was
      over-expression of almost all genes promoting vasoconstriction/ proliferation, as
      well as inflammation, and under-expression of all vasodilator/anti-proliferative
      genes. As expected, treatment with VIP fully corrected both the key PAH features,
      and all gene expression alterations. MCT-treated rats showed two distinct sets of
      alterations. One, similar to that in VIP(- /-) mice, i.e., tended to promote
      vascular remodeling and inflammation, e.g., up-regulation of myosin polypeptides,
      procollagen, and some inflammatory genes. The other was a set of opposite
      alterations that suggested an effort to modulate the PAH, e.g., up-regulation of
      the VIP and NOS3 genes. In this model, VIP treatment failed to correct many of
      the genotypic abnormalities, and, in parallel, incompletely corrected the
      phenotypic changes as well. This preliminary proof-of-concept study demonstrates
      the importance of genomic information in determining therapeutic outcome, and
      thus in selecting personalized therapy. Full validation of the merits of
      pharmacogenomics must await studies of lungs from patients with different forms
      of PAH.

PMID- 22140629
TI  - Idiopathic and heritable PAH perturb common molecular pathways, correlated with
      increased MSX1 expression.
AB  - The majority of pulmonary arterial hypertension (PAH) is not associated with
      BMPR2 mutation, and major risk factors for idiopathic PAH are not known. The
      objective of this study was to identify a gene expression signature for IPAH. To
      accomplish this, we used Affymetrix arrays to probe expression levels in 86
      patient samples, including 22 healthy controls, 20 IPAH patients, 20 heritable
      PAH patients (HPAH), and 24 BMPR2 mutation carriers that were as yet unaffected
      (UMC). Culturing the patient cells removes the signatures of drug effects and
      inflammation which have made interpretation of results from freshly isolated
      lymphocytes problematic. We found that gene expression signatures from IPAH
      patients clustered either with HPAH patients or in a single distinct group. There
      were no groups of genes changed in IPAH that were not also changed in HPAH. HPAH,
      IPAH, and UMC had common changes in metabolism, actin dynamics, adhesion,
      cytokines, metabolism, channels, differentiation, and transcription factors.
      Common to IPAH and HPAH but not UMC were an upregulation of vesicle trafficking,
      oxidative/nitrosative stress, and cell cycle genes. The transcription factor
      MSX1, which is known to regulate BMP signaling, was the most upregulated gene
      (4*) in IPAH patients. These results suggest that IPAH cases have a shared
      molecular origin, which is closely related to, but distinct from, HPAH. HPAH and
      IPAH share the majority of altered signaling pathways, suggesting that treatments
      developed to target the molecular etiology of HPAH will also be effective against
      IPAH.

PMID- 22140630
TI  - S1P(4) receptor mediates S1P-induced vasoconstriction in normotensive and
      hypertensive rat lungs.
AB  - This study aimed to identify receptors mediating sphingosine-1-phosphate (S1P)
      induced vasoconstriction in the normotensive and chronic hypoxia-induced
      hypertensive rat pulmonary circulation. In isolated perfused lungs from normoxic
      rats, infusion of S1P caused a sustained vasoconstriction, which was not reduced
      by combinational pretreatment with the dual S1P(1 and 3) receptor antagonist
      VPC23019 and the S1P(2) receptor antagonist JTE013. The S1P(4) receptor agonists
      phytosphingosine-1-phospate and VPC23153, but not the dual S1P(1 and 3) receptor
      agonist VPC24191, caused dose-dependent vasoconstrictions. In hypertensive lungs
      from chronically hypoxic rats, the vasoconstrictor responses to S1P and VPC23153
      were markedly enhanced. The S1P(4) receptor agonist VPC 23153 caused contraction
      of isolated pulmonary but not of renal or mesenteric arteries from chronically
      hypoxic rats. S1P(4) receptor protein as well as mRNA were detected in both
      normotensive and hypertensive pulmonary arteries. In contrast to what has been
      reported in the systemic circulation and mouse lung, our findings raise the
      possibility that S1P(4) receptor plays a significant role in S1P-induced
      vasoconstriction in the normotensive and hypertensive rat pulmonary circulation.

PMID- 22140631
TI  - Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle
      and endothelial cells.
AB  - Fenfluramine is prescribed either alone or in combination with phentermine as
      part of Fen-Phen, an anti-obesity medication. Fenfluramine was withdrawn from the
      US market in 1997 due to reports of heart valvular disease, pulmonary arterial
      hypertension, and cardiac fibrosis. Particularly, idiopathic pulmonary arterial
      hypertension (IPAH), previously referred to as primary pulmonary hypertension
      (PPH), was found to be associated with the use of Fen-Phen, fenfluramine, and
      fenfluramine derivatives. The underlying mechanism of fenfluramine-associated
      pulmonary hypertension is still largely unknown. We reasoned that investigating
      drug-induced gene dysregulation would enhance our understanding of the
      fenfluramine-associated pathogenic mechanism of IPAH. Whole-genome gene
      expression profiles in fenfluramine-treated human pulmonary artery smooth muscle
      (PASMC) and endothelial (PAEC) cells (isolated from normal subjects) were
      compared with baseline expression in untreated cells. Fenfluramine treatment
      caused dysregulation in a substantial number of genes involved in a variety of
      pathways and biological processes. In addition to several common pathways and
      biological processes such as "MAPK signaling pathway," "inflammation response,"
      and "calcium signaling pathway" shared between both cell types, pathways and
      biological processes such as "blood circulation," "muscle system process," and
      "immune response" were enriched among the dysregulated genes in PASMC. Pathways
      and biological processes such as those related to cell cycle, however, were
      enriched among the dysregulated genes in PAEC, indicating that fenfluramine could
      affect unique pathways (or differentially) in different types of pulmonary artery
      cells. While awaiting validation in a larger cohort, these results strongly
      suggested that fenfluramine could induce significant dysregulation of genes in
      multiple biological processes and pathways critical for normal pulmonary vascular
      functions and structure. The transcriptional and posttranscriptional changes in
      these genes may, therefore, contribute to the pathogenesis of fenfluramine
      associated IPAH.

PMID- 22140633
TI  - Isolated large vessel pulmonary vasculitis as a cause of chronic obstruction of
      the pulmonary arteries.
AB  - Isolated pulmonary artery involvement by large vessel vasculitis is rare. This
      case report describes two patients with large vessel pulmonary vasculitis
      initially thought to have chronic thromboembolic pulmonary hypertension who had
      their diagnosis revised following pulmonary endarterectomy surgery. Advances in
      imaging techniques such as positron emission tomography and magnetic resonance
      imaging have permitted complementary radiological methods of diagnosis and follow
      up of large vessel disease and these are discussed in conjunction with the
      immunosuppressive and operative management of these patients.

PMID- 22140632
TI  - Neurogenic responses in rat and porcine large pulmonary arteries.
AB  - Pharmacological differences between neurogenic sympathetic responses in rat and
      pig isolated pulmonary arteries were examined in strip preparations. Electrical
      field stimulation in the range of 0.6 to 40 Hz resulted in frequency-dependent
      contractions in terms of amplitude and rate of rise. Responses in the rat
      declined sharply from pulmonary trunk to main artery; in contrast, in the pig
      they continued into the third-order vessels. Contractions were inhibited in the
      presence of tetrodotoxin, prazosin or WB-4101 and hence neurogenic in origin.
      Cocaine enhanced field stimulated contractions in both rat and porcine tissues;
      however, the effect in the former was of significantly greater magnitude in terms
      of either area under the mechanogram or height of contraction. In addition, the
      rate of rise, time to peak and duration of peak were all increased in the rat but
      less so or not in the pig. Field stimulated contractions were virtually abolished
      by guanethidine (1*10(-6) M) in rat but not in porcine pulmonary arteries in
      which a ten-fold higher concentration significantly reduced neurogenic
      contractions and abolished them in 2 out of 4 tissues tested. The effect of
      guanethidine (1*10(-6) M) observed in blood vessels of rat exceeded about five
      fold that observed in porcine tissues. Thus, neurogenic responses appear to be
      entirely mediated by extra-junctional alpha(1)-adrenoceptors in both species, and
      in contrast to the rat, pig tissues seem to have a noradrenaline re-uptake that
      is either less efficient or operating near saturation.

PMID- 22140634
TI  - Survival in pulmonary arterial hypertension: A brief review of registry data.

PMID- 22140635
TI  - Persistent Organochlorine Exposure and Pregnancy Loss: A Prospective Cohort
      Study.
AB  - Polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene
      (DDE) are suspected reproductive toxicants. We assessed serum concentration of 76
      PCB congeners, DDE, and risk of human chorionic gonadotropin confirmed pregnancy
      loss among 79 women followed for up to 12 menstrual cycles or until pregnancy. 55
      women had live births, 14 experienced pregnancy losses, and 10 did not achieve
      pregnancy. PCBs and DDE were quantified using gas chromatography with electron
      capture. PCBs were grouped a priori by biologic activity. Cox proportional hazard
      regression adjusting for age (categorized 24 - 29, 30 - 34) and average
      standardized alcohol and cigarette intake (continuous) was used to estimate
      hazard ratios (HR) of pregnancy loss. Estrogenic PCBs (HR = 1.66, 95% CI: 0.68,
      4.02), anti-estrogenic PCBs (HR = 0.10, 95% CI: <0.01, 67.07) and DDE (HR = 1.43,
      95% CI: 0.45, 4.52) were not statistically significantly associated with
      pregnancy loss. Our results provide some signal that estrogenic and
      antiestrogenic PCBs may be differentially associated with pregnancy loss. Further
      research is needed to elucidate these associations.

PMID- 22140637
TI  - Comparison of tertiary-center aneurysm location frequencies in 400 consecutive
      cases: Decreasing incidence of posterior communicating artery region aneurysms.
AB  - BACKGROUND: The growing number of community hospitals with neurointerventional
      services over the past decade has changed the type and complexity of cerebral
      aneurysms referred to tertiary centers. The authors hypothesized that this would
      be reflected in changes in the location frequencies of aneurysms treated now
      compared to before the widespread institution of endovascular coiling. METHODS:
      Using a prospectively collected aneurysm database, aneurysm location frequencies
      were retrospectively reviewed for the last 200 consecutively treated aneurysms
      (2009-2010) and 200 consecutive aneurysms treated starting from May 1999 to
      December 2000. International Subarachnoid Aneurysm Trial (ISAT) aneurysm location
      nomenclature was utilized. Two-tailed Student's t-tests were used to compare
      means and Fisher exact tests were used to compare proportions. RESULTS: The
      location frequencies of all aneurysms (ruptured and unruptured) treated in the
      2000 epoch as compared to the modern epoch showed significant changes for middle
      cerebral aneurysms (12.0% vs. 21.0%, P = 0.014), posterior communicating (21.0%
      vs. 13.0%, P = 0.0001), and para-ophthalmic aneurysms (10.0% vs. 25.5%, P =
      0.0002). For unruptured/elective aneurysms, the change in posterior communicating
      aneurysms was even more pronounced (27.8% vs 3.6%, P = 0.0001). The rate of
      aneurysm coiling at the center rose from 26% to 37% (P = 0.02). CONCLUSIONS: The
      significant reduction in the referrals to our tertiary center of less technically
      complex aneurysms (posterior communicating segment) and increased referrals of
      aneurysms not as amenable to coil embolization (middle cerebral artery) is likely
      attributable to the growth of neurointerventional services at community hospitals
      over the past 10 years.

PMID- 22140636
TI  - AGING OF THE SUBVENTRICULAR ZONE NEURAL STEM CELL NICHE.
AB  - The persistence of an active subventricular zone neural stem cell niche in the
      adult mammalian forebrain supports its continued role in the production of new
      neurons and in generating cells to function in repair through adulthood.
      Unfortunately, with increasing age the niche begins to deteriorate, compromising
      these functions. The reasons for this decline are not clear. Studies are
      beginning to define the molecular and physiologic changesin the microenvironment
      of the aging subventricular zone niche. New revelations from aging studies will
      allow for a more thorough understanding of what reparative functions are lost in
      the aged brain, the progression of niche demise and the possibility for
      therauptic intervention to improve aging brain function.

PMID- 22140638
TI  - Familial glioblastoma: A case report of glioblastoma in two brothers and review
      of literature.
AB  - BACKGROUND: Gliomas that aggregate in families with history of malignancy may
      have an inheritable genetic basis. Gliomas can occur in several well known tumor
      syndromes. However, their occurrence in the absence of these syndromes is quite
      rare. High-grade gliomas, such as glioblastoma multiforme (GBM), are the most
      common and most lethal primary cancers of the central nervous system (CNS). CASE
      DESCRIPTION: We present a case of two brothers both diagnosed with GBM. Both
      siblings underwent biopsy with debulking of the tumors by different surgeons.
      Only one sibling elected to undergo chemotherapy and radiation. Cytogenetic
      studies were possible only on one sibling and the tumor specimen revealed
      multiple chromosomal abnormalities, including triploidies 4, 8, 12, 22 and loss
      of heterozygosity of 1p, 9p, and 10. Histological samples for both tumors were
      similar, both revealing increased cellularity consisting of gemistocytic
      astrocytes, central necrosis, and microvascularization. CONCLUSION: We present
      two brothers who display a rare familial relationship in the development of their
      GBMs. Supplementary and improved genetic studies may allow for specific treatment
      modalities as certain genetic abnormalities have better response to tailored
      treatments and carry better prognoses.

PMID- 22140639
TI  - Surgical approaches to tinnitus treatment: A review and novel approaches.
AB  - BACKGROUND: Tinnitus, a profoundly widespread auditory disorder, is characterized
      by the perception of sound in the absence of external stimulation. The aim of
      this work is to review the various surgical treatment options for tinnitus,
      targeting the various disruption sites along the auditory pathway, as well as to
      indicate novel neuromodulatory techniques as a mode of tinnitus control. METHODS:
      A comprehensive analysis was conducted on published clinical and basic
      neuroscience research examining the pathophysiology and treatment options of
      tinnitus. RESULTS: Stereotactic radiosurgery methods and microvascular
      decompressions are indicated for tinnitus caused by underlying pathologies such
      as vestibular schwannomas or neurovascular conflicts of the vestibulocochlear
      nerve at the level of the brainstem. However, subsequent hearing loss and
      secondary tinnitus may occur. In patients with subjective tinnitus and
      concomitant sensorineural hearing loss, cochlear implantation is indicated.
      Surgical ablation of the cochlea, vestibulocochlear nerve, or dorsal cochlear
      nucleus, though previously suggested in earlier literature as viable treatment
      options for tinnitus, has been shown to be ineffective and contraindicated.
      Recently, emerging research has shown the neuromodulatory capacity of the
      somatosensory system at the level of the trigeminal nerve on the auditory pathway
      through its inputs at various nuclei in the central auditory pathway. CONCLUSION:
      Tinnitus remains to be a difficult disorder to treat despite the many surgical
      interventions aimed at eliminating the aberrant neuronal activity in the auditory
      system. A promising novel neuromodulatory approach using the trigeminal system to
      control such a bothersome and difficult-to-treat disorder deserves further
      investigation and controlled clinical trials.

PMID- 22140640
TI  - Intraspinal primitive neuroectodermal tumor in a man with neurofibromatosis type
      1: Case report and review of the literature.
AB  - BACKGROUND: The occurrence of primitive neuroectodermal tumors (PNET) in patients
      with neurofibromatosis type 1 (NF1) has only been reported in two other cases in
      English-Language literature. Owing to the rarity of intraspinal PNET and the
      extremely high gene mutation variability in NF1, there is currently no conclusive
      evidence to suggest that PNET is associated with NF1. Here, we report a case of
      intradural PNET in a patient with NF1. CASE DESCRIPTION: A 27-year-old male
      underwent a C1-C3 laminectomy for resection of an intramedullary mass.
      Histopathology and immunohistopathology analysis was performed. Microscopic
      examination and immunohistochemical staining indicated the mass was a primitive
      neuroectodermal tumor. Within 1 month after tumor resection, the patient
      developed leptomeningeal carcinomatosis. The patient was not a candidate for
      radiation therapy but underwent palliative systemic chemotherapy. He subsequently
      developed neutropenia and died 3 months after tumor resection. CONCLUSION: To our
      knowledge, this is the first reported intraspinal PNET associated with NF1.
      Genetic analysis of CNS PNETs suggests a possible correlation, but larger case
      series are needed to support this theory.

PMID- 22140641
TI  - Anterior decompression, fusion and plating in cervical spine injury: Early
      experience in Abuja, Nigeria.
AB  - BACKGROUND: We present a review of the results of the current surgical management
      of acute cervical spine injuries in the Federal Capital Territory, Abuja,
      Nigeria. This is the first detailed retrospective study on the surgical
      management of patients with cervical spine injuries from Nigeria. METHODS: The
      medical reports of patients with traumatic cervical spine and spinal cord
      injuries undergoing surgery from 1 August 2009 till 30 August 2010 were reviewed.
      Management and early results of outcome were ascertained and detailed
      consecutively in a prospective Microsoft Office Access((r)) database (Microsoft
      Group of Companies). Frankel grading was used for pre- and immediate post
      operative evaluation (within 48 hours). The Barthel index (BI) was used to
      classify patients as dependent or independent at follow-up. RESULTS: Twenty
      consecutive patients presented with acute cervical spine and spinal cord injuries
      since August 2009. Twenty anterior cervical spine decompression and fixation with
      an iliac graft and an anterior cervical plate (ACDF) were performed in 18
      patients. All operations were performed with general anaesthesia using standard
      techniques but without a microscope or a high speed drill. Of the 18 patients who
      were operated, 4 patients died within a short period following surgical
      intervention. Seven patients have made a full recovery and seven remain fully
      dependent. Only two of the dependent quadriplegic patients have become
      reintegrated back into the society. CONCLUSION: The management of spinal cord
      injuries in Abuja is evolving. The operations were performed adequately with much
      limited complement of equipment. Poor intensive care therapy is a major challenge
      and improvements in this area of care will likely lead to better patient
      outcomes.

PMID- 22140642
TI  - In situ free-floating craniectomy for traumatic cerebral decompression in an
      infant: A field hospital solution.
AB  - BACKGROUND: Despite refinements in neurotrauma care, the morbidity and mortality
      of severe traumatic brain injury (TBI) in pediatric patients remains high. We
      report a novel approach to the surgical management of increased intracranial
      pressure in severe TBI utilizing an in situ free-floating craniectomy technique,
      which was originally devised as a creative solution to the unique challenges in a
      Haitian field hospital following the 2010 earthquake. CASE DESCRIPTION: A 13
      month-old Haitian boy presented to Project Medishare field hospital in Port-au
      Prince with left hemiplegia, a bulging fontanelle, and increasing lethargy
      following a traumatic head injury 4 days prior. An urgent craniectomy was
      performed based on clinical grounds (no brain imaging was available). A standard
      trauma flap incision was made, followed by a hemicraniectomy and expansion
      duraplasty. A small hematoma was evacuated. Frontal, temporal, and parietal bone
      flaps were placed on the dura in approximation to their normal anatomical
      configuration, but not affixed, leaving space for further brain edema, and the
      scalp was closed. The child experienced favorable peri-operative and early
      postoperative results. CONCLUSION: In situ free-floating craniectomy, while
      devised as a creative solution to limited resources in a natural disaster zone,
      may offer advantages over more traditional techniques.

PMID- 22140643
TI  - Benefits and limitations of diameter measurement in the conservative management
      of meningiomas.
AB  - BACKGROUND: Meningiomas are the most common benign brain tumors that are
      frequently followed-up by neurologists, general practitioners, and neurosurgeons.
      Some recent studies advocate the accurate volumetric method (VM) over measuring
      the linear maximum diameter although its clinical significance still remains
      unknown. The aim of this study is to directly compare the linear method (LM) and
      VM to delineate the characteristics of both measurements. METHODS: Between 2003
      and 2010, growth analysis using magnetic resonance imaging DICOM files was
      performed for 189 meningiomas in 161 patients at the Cleveland Clinic. In LM, a
      minimum increase of 2 mm in maximum diameter was defined as tumor growth. The
      absolute volume growth (VG, in cm(3)) was calculated for each tumor. RESULTS:
      Linear growth (LG) was seen in 71 tumors (37.6%) within the median follow-up of
      2.0 years. These tumors with LG showed a mean VG of 2.80 cm(3). Some large LG
      positive tumors can be larger than estimated from LG. In addition, the skull base
      location was correlated to greater VG. On the other hand, 118 tumors without LG
      demonstrated the minimal actual volume increase, i.e., mean VG of 0.16 cm(3).
      Although a small subset of these LG-negative tumors might have slightly high VG
      when they were large, the location of tumor had no correlation to VG.
      CONCLUSIONS: Our data demonstrated some important precautions in measuring the
      tumor growth. We believe that it is mandatory in the conservative management of
      meningiomas to correctly understand benefits and potential limitations of
      different measurement methods utilized.

PMID- 22140644
TI  - Surgical treatment of cerebellar metastases.
AB  - BACKGROUND: Cerebral metastases are a common neurosurgical finding. Surgery
      confers several advantages to other therapies, including immediate symptomatic
      improvement, diagnosis, and relief from corticosteroid dependence. Here we
      evaluate patients with cerebellar metastases who underwent surgery and compare
      their findings to those in the literature, and address the benefit of avoiding
      ventriculo-peritoneal shunting in patients undergoing surgery. METHODS: We
      performed a retrospective analysis involving 50 patients with cerebellar
      metastases who underwent surgical resection. Ventriculo-peritoneal shunts were
      placed in patients necessitating permanent CSF drainage. We evaluated
      presentation, diagnosis, complications, and outcome. RESULTS: Our review included
      21 males and 29 females, 29 to 82 years of age. Primary tumors included lung
      (48%), breast (14%), GI (14%), endometrial/ovarian (6%), melanoma (6%), sarcoma
      (4%), lymphoma (4%), laryngeal (2%), and other (2%). Clinical symptoms at
      presentation commonly were those secondary to elevated intracranial pressure and
      were the initial complaint in 34% of patients. Preoperatively, 29 patients were
      noted to have hydrocephalus. Importantly, 76% of these patients were able to
      avoid placement of a ventriculo-peritoneal shunt following surgery. Only two
      complications were noted in our series of 50 patients, including a symptomatic
      pseudomeningocele and a wound infection. No symptomatic postoperative hematoma
      developed in any surgical case. CONCLUSION: A review of the literature has shown
      a high complication rate in patients undergoing surgical resection of cerebellar
      metastases. We have shown that surgical resection of cerebellar metastases is a
      safe procedure and is effective in the treatment of hydrocephalus in the majority
      of patients harboring cerebellar lesions.

PMID- 22140645
TI  - Neurosurgical management of leukoencephalopathy, cerebral calcifications, and
      cysts: A case report and review of literature.
AB  - BACKGROUND: Leukoencephalopathy, Calcification, and Cyst (LCC) is a syndrome
      describing the rare concurrence of these three unusual radiographic findings.
      Here, we describe the neurosurgical management in a patient afflicted with LCC
      and review the existing literature on surgical indications and outcomes. CASE
      DESCRIPTION: A 24-year-old man presented with symptoms of progressive headache,
      gait imbalance and horizontal diplopia. Magnetic resonance imaging (MRI) showed
      radiographic findings typically associated with LCC, including a large pontine
      cyst with significant mass effect. The patient's symptoms resolved after open
      surgical cyst drainage. However, he suffered cyst re-accumulation 3 months after
      the initial procedure and ultimately underwent placement of a ventriculo-cysto
      peritoneal shunt. At the 3-year follow-up, the patient remained symptom free with
      continued cyst decompression. CONCLUSION: Our case report suggests that
      ventriculo-cysto-peritoneal shunting appeared an effective strategy in LCC
      patients in whom the cyst fenestration failed. We present this case report in the
      context of the first systematic review of literature on neurosurgical management
      strategies for patients afflicted with LCC.

PMID- 22140646
TI  - Stalin's mysterious death.

PMID- 22140647
TI  - Mycobacterium bovis spondylodiscitis after intravesical Bacillus Calmette-Guerin
      therapy.
AB  - BACKGROUND: Intravesical instillations of live-attenuated Bacillus Calmette
      Guerin (BCG) are a well-known and effective method for prevention and treatment
      of bladder carcinoma and carcinoma in situ. Although considered a safe procedure
      with rare side effects, local and systemic complications may occur. While long
      bone ostemolyelitis has been well described, very few reports of BCG
      spondylodiscitis exist in the literature. CASE DESCRIPTION: A 67-year-old man
      developed low back pain, anorexia, and weight loss 11 months after a 6-week
      course of intravesical BCG instillations for the treatment of bladder carcinoma
      in situ. Imaging studies revealed L1-L2 spondylodiscitis with epidural and
      bilateral psoas abscesses. Tissue cultures obtained by percutaneous computed
      tomography-guided aspiration were positive for Mycobacterium bovis. Despite
      triple antituberculous therapy (isoniazid, rifampin, and ethambutol), clinical
      and radiological progression occurred. Therefore, L1 and L2 corpectomies with
      extensive debridement were performed, followed by 360 degrees  anterior-posterior
      instrumented fusion. After 20 months of follow-up, the patient remains
      asymptomatic and recurrence-free. CONCLUSION: Mycobacterium bovis
      spondylodiscitis is a rare complication of intravesical BCG therapy. Although
      medical therapy with antituberculous agents is the first-line treatment, surgical
      decompression, debridement, and stabilization may be necessary in refractory
      cases.

PMID- 22140649
TI  - Usefulness of the contralateral Omega sign for the topographic location of
      lesions in and around the central sulcus.
AB  - BACKGROUND: The central sulcus may be located through magnetic resonance imaging
      (MRI) by identifying the ipsilateral inverted Omega shape. In a brain with a
      lesion in this area, its identification becomes a hard task irrespective of the
      technique applied. The aim of this study is to show the usefulness of the
      contralateral Omega sign for the location of tumors in and around the central
      sulcus. We do not intend to replace modern techniques, but to show an easy, cheap
      and relatively effective way to recognize the relationship between the central
      sulcus and the lesion. METHODS: From July 2005 through December 2010, 43 patients
      with lesions in and around the central sulcus were operated using the
      contralateral Omega sign concept. Additionally, 5 formalin-fixed brains (10
      hemispheres) were studied to clarify the anatomy of the central sulcus where the
      Omega shape is found. RESULTS: The central sulcus has three genua. The middle
      genu is characterized by an inverted Omega-shaped area in axial sections known as
      the Omega sign. On anatomical specimens, Omega was 11.2 +/- 3.35 mm in height, on
      average, and 18.7 +/- 2.49 mm in width, at the base. The average distance from
      the medial limit of the Omega to the medial edge of the hemisphere was 24.5 +/-
      5.35 mm. Identification of the Omega sign allowed for the topographic
      localization of the contralateral central sulcus in all our surgical cases but
      one. CONCLUSION: The contralateral Omega sign can be easily and reliably used to
      clarify the topographic location of the pathology. Hence, it gives a quick
      preoperative idea of the relationships between the lesion and the pre- and post
      central gyri.

PMID- 22140648
TI  - The therapeutic potential of inhibitors of the signal transducer and activator of
      transcription 3 for central nervous system malignancies.
AB  - BACKGROUND: High-grade primary and metastatic central nervous system (CNS) tumors
      are common, deadly, and refractory to conventional therapy and continue to be
      therapeutically challenging. A key nodal transcriptional factor, the signal
      transducer and activator of transcription 3 (STAT3), drives the fundamental
      components of tumor malignancy and metastases in the CNS by enhancing
      proliferation, angiogenesis, invasion, metastasis, and immunosuppression. The
      introduction of STAT3 inhibitors in clinical trials for this patient population
      is imminent. METHODS: STAT3 inhibitors have been extensively tested in a variety
      of preclinical murine models. RESULTS: The STAT3 inhibitor, WP1066, has displayed
      marked efficacy with minimal toxicity against malignancy in murine models,
      including established intracerebral tumors. The mechanism of this in vivo
      efficacy of the STAT3 blockade agents is a combination of direct tumor
      cytotoxicity and immune cytotoxic clearance. CONCLUSIONS: Given their direct
      antitumor cytotoxic effects, STAT3 inhibitors may exert therapeutic activity in
      the monotherapy setting but may also have compelling use as immunotherapeutic
      modulators or as a salvage therapy.

PMID- 22140650
TI  - THE IMPACT OF SEXUAL HARASSMENT ON DEPRESSIVE SYMPTOMS DURING THE EARLY
      OCCUPATIONAL CAREER.
AB  - Sexual harassment has been theorized as a stressor with consequences for the
      physical and mental health of its targets. Though social scientists have
      documented a negative association between sexual harassment and mental health,
      few longitudinal studies have investigated the association between sexual
      harassment and depressive symptoms. Using longitudinal survey data from the Youth
      Development Study, combined with in-depth interviews, this article draws on
      Louise Fitzgerald's theoretical framework, stress theory, and the life course
      perspective to assess the impact of sexual harassment on depressive affect during
      the early occupational career. In support of Fitzgerald's model, our findings
      confirm that sexual harassment is a stressor that is associated with increased
      depressive symptoms. Our quantitative results show that women and men who
      experience more frequent sexual harassment at work have significantly higher
      levels of depressed mood than non-harassed workers, even after controlling for
      prior harassment and depressive symptoms. Moreover, we find evidence that sexual
      harassment early in the career has long-term effects on depressive symptoms in
      adulthood. Interviews with a subset of our survey respondents point to a variety
      of coping strategies and reveal further links between harassment and other
      aspects of mental health, such as anger and self-doubt.

PMID- 22140651
TI  - Development and Evaluation of CmeC Subunit Vaccine against Campylobacter jejuni.
AB  - Campylobacter jejuni is the leading bacterial cause of human enteritis in many
      industrialized countries. There is no commercial vaccine against C. jejuni
      available to date. CmeC is an essential outer membrane component of CmeABC
      multidrug efflux pump that plays a critical role in antibiotic resistance and in
      vivo colonization of C. jejuni. CmeC is prevalent in C. jejuni strains and is
      dramatically induced and immunogenic in vivo. In this study, we analyzed CmeC
      sequence homology, examined in vitro immune protection of CmeC peptide
      antibodies, and produced full-length recombinant CmeC (rCmeC) for evaluating
      immunogenicity and protective efficacy of the CmeC subunit vaccine against C.
      jejuni using chicken model system. Amino acid sequences of CmeC from 24 diverse
      C. jejuni strains were determined and subjected to alignment, which revealed that
      CmeC is highly conserved in C. jejuni with a identity ranging from 97.3% to 100%.
      CmeC peptide antibodies inhibited the function of CmeABC efflux pump and enhanced
      susceptibility of C. jejuni to bile salts, the natural antimicrobial present in
      the intestine. Two full-length rCmeC proteins with N- or C-terminal His tag were
      produced in E. coli; the N-terminal His-tagged rCmeC with high purity and yield
      was obtained by single step affinity purification. The purified rCmeC was used in
      two vaccination trials using a chicken model of C. jejuni infection. Stimulation
      of CmeC-specific serum IgG responses via oral vaccination required immunization
      with higher doses of rCmeC (200MUg) together with 70MUg of mucosal adjuvant mLT
      (modified E. coli heat-labile enterotoxin). Subcutaneous vaccination of chickens
      with rCmeC remarkably stimulated both serum IgG and IgA responses. However, CmeC
      specific intestinal secretory IgA response was not significantly stimulated
      regardless of vaccination regimen and the rCmeC vaccination did not confer
      protection against C. jejuni infection. Together, these findings provide further
      compelling evidence that CmeC is a promising subunit vaccine candidate against C.
      jejuni infection. However, the CmeC vaccination regimen should be optimized to
      enhance CmeC-specific mucosal immune response in for protection against C.
      jejuni.

PMID- 22140652
TI  - Characterization of KRAS rearrangements in metastatic prostate cancer.
AB  - Using an integrative genomics approach called amplification breakpoint ranking
      and assembly analysis, we nominated KRAS as a gene fusion with the ubiquitin
      conjugating enzyme UBE2L3 in the DU145 cell line, originally derived from
      prostate cancer metastasis to the brain. Interestingly, analysis of tissues
      revealed that 2 of 62 metastatic prostate cancers harbored aberrations at the
      KRAS locus. In DU145 cells, UBE2L3-KRAS produces a fusion protein, a specific
      knockdown of which attenuates cell invasion and xenograft growth. Ectopic
      expression of the UBE2L3-KRAS fusion protein exhibits transforming activity in
      NIH 3T3 fibroblasts and RWPE prostate epithelial cells in vitro and in vivo. In
      NIH 3T3 cells, UBE2L3-KRAS attenuates MEK/ERK signaling, commonly engaged by
      oncogenic mutant KRAS, and instead signals via AKT and p38 mitogen-activated
      protein kinase (MAPK) pathways. This is the first report of a gene fusion
      involving the Ras family, suggesting that this aberration may drive metastatic
      progression in a rare subset of prostate cancers. SIGNIFICANCE: This is the first
      description of an oncogenic gene fusion of KRAS, one of the most studied proto
      oncogenes. KRAS rearrangement may represent the driving mutation in a rare subset
      of metastatic prostate cancers, emphasizing the importance of RAS-RAF-MAPK
      signaling in this disease.

PMID- 22140655
TI  - Preparation, Characterization and Application of Optical Switch Probes.
AB  - Optical switches represent a new class of molecular probe with applications in
      high contrast imaging and optical manipulation of protein interactions. Small
      molecule, organic optical switches based on nitrospirobenzopyran (NitroBIPS) and
      their reactive derivatives and conjugates undergo efficient, rapid and
      reversible, orthogonal optically-driven transitions between a colorless spiro
      (SP) state and a colored merocyanine (MC) state. The excited MC-state also emits
      fluorescence, which serves as readout of the state of the switch. Defined optical
      perturbations of SP and MC generate a defined waveform of MC-fluorescence that
      can be isolated against unmodulated background signals by using a digital optical
      lock-in detection approach or to control specific dipolar interactions on
      proteins. The protocols describe general procedures for the synthesis and
      spectroscopic characterization of NitroBIPS and specifically labeled conjugates
      along with methods for the manipulation of dipolar interactions on proteins and
      imaging of the MC-state of NitroBIPS within living cells.

PMID- 22140653
TI  - mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT
      signaling.
AB  - mTOR kinase inhibitors block mTORC1 and mTORC2 and thus do not cause the mTORC2
      activation of AKT observed with rapamycin. We now show, however, that these drugs
      have a biphasic effect on AKT. Inhibition of mTORC2 leads to AKT serine 473
      (S473) dephosphorylation and a rapid but transient inhibition of AKT T308
      phosphorylation and AKT signaling. However, inhibition of mTOR kinase also
      relieves feedback inhibition of receptor tyrosine kinases (RTK), leading to
      subsequent phosphoinositide 3-kinase activation and rephosphorylation of AKT T308
      sufficient to reactivate AKT activity and signaling. Thus, catalytic inhibition
      of mTOR kinase leads to a new steady state characterized by profound suppression
      of mTORC1 and accumulation of activated AKT phosphorylated on T308, but not S473.
      Combined inhibition of mTOR kinase and the induced RTKs fully abolishes AKT
      signaling and results in substantial cell death and tumor regression in vivo.
      These findings reveal the adaptive capabilities of oncogenic signaling networks
      and the limitations of monotherapy for inhibiting feedback-regulated pathways.
      SIGNIFICANCE: The results of this study show the adaptive capabilities of
      oncogenic signaling networks, as AKT signaling becomes reactivated through a
      feedback-induced AKT species phosphorylated on T308 but lacking S473. The
      addition of RTK inhibitors can prevent this reactivation of AKT signaling and
      cause profound cell death and tumor regression in vivo, highlighting the possible
      need for combinatorial approaches to block feedback-regulated pathways.

PMID- 22140654
TI  - A novel two-stage, transdisciplinary study identifies digoxin as a possible drug
      for prostate cancer treatment.
AB  - Identification of novel indications for commonly prescribed drugs could
      accelerate translation of therapies. We investigated whether any clinically-used
      drugs might have utility for treating prostate cancer by coupling an efficient,
      high-throughput laboratory-based screen and a large, prospective cohort study. In
      stage 1, we conducted an in vitro prostate cancer cell cytotoxicity screen of
      3,187 compounds. Digoxin emerged as the leading candidate given its potency in
      inhibiting proliferation in vitro (mean IC50=163 nM) and common use. In stage 2,
      we evaluated the association between the leading candidate drug from stage 1 and
      prostate cancer risk in 47,884 men followed 1986-2006. Regular digoxin users
      (versus nonusers: RR=0.76, 95% CI 0.61-0.95), especially users for >= 10 years
      (RR=0.54, 95% CI 0.37-0.79, P-trend<0.001), had a lower prostate cancer risk.
      Digoxin was highly potent in inhibiting prostate cancer cell growth in vitro and
      its use was associated with a 25% lower prostate cancer risk. SIGNIFICANCE: Our
      two-stage transdisciplinary approach for drug repositioning provides compelling
      justification for further mechanistic and possibly clinical testing of the
      leading nonchemotherapy candidate, digoxin, a cardiac glycoside, as a drug for
      prostate cancer treatment. Perhaps of equal importance, our study illustrates the
      power of the transdisciplinary approach in translational cancer research. By
      coupling laboratory and epidemiologic methods and thinking, we reduced the
      probability of identifying false-positive candidate drugs for the next steps in
      testing.

PMID- 22140656
TI  - Subsets of Spiny Striosomal Striatal Neurons Revealed in the Gad1-GFP BAC
      Transgenic Mouse.
AB  - OBJECTIVE: To characterize GFP-expressing cells in the striatum of Cb6-Tg(Gad1
      EGFP)G42Zjh/J mice, in which the Gad1 (also referred to as GAD67) promoter drives
      GFP expression (Gad1-GFP mouse).  BACKGROUND: GFP-expressing cells of the GAD1
      GFP mouse have been described to be a population of parvalbumin-positive basket
      interneurons residing in the cerebral cortex and the cerebellum. However, the
      cells in the dorsal striatum of these mice have not been characterized.  METHODS:
      Using a combination of immunohistochemistry, electrophysiology, DiI labeling, and
      retrograde tracing, we investigated the phenotypes of GFP-expressing cells in the
      GAD1-GFP mice.  RESULTS: A small number of striatal neurons express GFP in these
      mice. In the mature striatum, these cells are preferentially located in the
      lateral striatum with a strong expression in the lateral striatal streak. The
      GAD1-GFP positive neurons are distinct from the standard fast-spiking and low
      threshold-spiking GAD-67 expressing striatal interneurons and appear to be a
      subset of medium spiny neurons. These neurons are generally colocalized with
      striosomal markers such as dynorphin, mu-opioid receptors, as well as CB1 and
      calretinin-immunopositive fibers. Striatal Gad1-GFP neurons can be separated into
      two groups based on the shape of the somata and patterns of action potential
      firing. Retrograde labeling indicated that a proportion of these cells are
      projection neurons.  CONCLUSIONS: The examination of GAD1-GFP cells in these mice
      revealed 2 subpopulations of ventral striosomal striatal medium spiny neurons,
      based on morphology, patch-matrix segregation and membrane properties.

PMID- 22140657
TI  - A Multiple Geometric Deformable Model Framework for Homeomorphic 3D Medical Image
      Segmentation.
AB  - This paper presents a 3D segmentation framework for multiple objects or
      compartments embedded as level sets. Thanks to a compact representation of the
      level set functions of multiple objects, the framework guarantees no overlap and
      vacuum, and leads to a computationally efficient evolution scheme largely
      independent of the number of objects. Appropriate topology constraints ensure not
      only that the topology of each object remains the same, but that the relationship
      between objects is also maintained. The decomposition of objects makes the
      framework specifically attractive to the segmentation of related anatomical
      regions or the parcellation of an organ, where relationships must be maintained
      and different evolution forces are needed on different parts of the objects
      interface. Examples of 3D whole brain segmentation and thalamic parcellation
      demonstrate the potential of our method for such segmentation tasks.

PMID- 22140658
TI  - Clinical parameters of inflammatory bowel disease in children do not correlate
      with four common polymorphisms of the transforming growth factor beta1 gene.
AB  - Transforming growth factor beta1 (TGF-beta1) is a cytokine affecting cell
      proliferation and development, which also has an immunomodulatory activity.
      Correlations between polymorphisms of the TGF-beta1 gene and clinical parameters
      of inflammatory bowel disease (IBD) were reported previously in adults. Here, we
      tested whether such correlations occur in pediatric patients suffering from IBD.
      One hundred and four pediatric IBD patients were involved in this study. Among
      them, 36 were diagnosed with Crohn's Disease (CD) and 68 were diagnosed with
      ulcerative colitis (UC). The control group consisted of 103 children, in which
      IBD was excluded. TGF-beta1 levels were determined in plasma and intestinal
      mucosa samples. The presence of the TGF beta1 protein and the amount of TGF beta1
      mRNA were estimated in intestinal mucosa by immunohistochemistry and reverse
      transcription Real-Time PCR, respectively. Four common polymorphisms of the TGF
      beta1 gene were investigated: -800G/A, -509C/T, 869T/C and 915G/C. No significant
      correlation between TGF-beta1 genotypes and (i) TGF-beta1 levels in plasma and
      tissue samples, (ii) TGF-beta1 gene expression efficiency in intestinal mucosa,
      (iii) IBD clinical parameters and (iv) inflammatory activity could be detected in
      children suffering from IBD. We conclude that, contrary to previous suggestions,
      the four common polymorphisms of the TGF-beta1 gene do not influence the
      susceptibility to or clinical parameters of IBD in the tested population of
      children.

PMID- 22140659
TI  - Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with
      non-alcoholic fatty liver disease.
AB  - OBJECTIVES: There is a need to replace liver biopsy with non-invasive markers
      that predict the degree of liver fibrosis in fatty liver disease related to
      obesity. Therefore, we studied four potential serum markers of liver fibrosis and
      compared them with histopathological findings in liver biopsy in children with
      non-alcoholic fatty liver disease (NAFLD). METHODS: We determined fasting serum
      level of hyaluronic acid (HA), laminin, YKL-40 and cytokeratin-18 M30 in 52
      children (age range 4-19, mean 12 years, 80 % of them were overweight or obese)
      with biopsy-verified NAFLD. Viral hepatitis, autoimmune and metabolic liver
      diseases (Wilson's disease, alpha-1-antitrypsin deficiency, cystic fibrosis) were
      excluded. Fibrosis stage was assessed in a blinded fashion by one pathologist
      according to Kleiner. Receiver operating characteristics (ROC) analysis was used
      to calculate the power of the assays to detect liver fibrosis (AccuROC, Canada).
      RESULTS: Liver fibrosis was diagnosed in 19 children (37 %). The levels of HA and
      CK18M30 were significantly higher in children with fibrosis compared to children
      without fibrosis (p=0.04 and 0.05 respectively). The ability of serum HA (cut-off
      19.1 ng/ml, Se=84 %, Sp=55 %, PPV=52 %, NPV=86 %) and CK18M30 (cut-off 210 u/l,
      Se=79 %, Sp=60 %, PPV=56 %, NPV=82 %) to differentiate children with fibrosis
      from those without fibrosis was significant (AUC=0.672 and 0.666, respectively).
      The combination of both markers was superior (AUC=0.73, p=0.002). Laminin and YKL
      40 levels did not allow a useful prediction. CONCLUSIONS: Cytokeratin-18 and
      hyaluronic acid are suitable serum markers predicting liver fibrosis in children
      with NAFLD. Studying these markers may identify patients at risk of disease
      progression.

PMID- 22140660
TI  - Bone augmentation of the atrophic posterior mandible for dental implants using
      rhBMP-2 and titanium mesh: clinical technique and early results.
AB  - The atrophic posterior mandible has unique challenges when implant placement is
      planned. The purpose of this case series was to evaluate the use of recombinant
      human bone morphogenetic protein 2/acelluar collagen sponge (rhBMP-2/ACS) and
      titanium mesh for augmentation of the atrophic posterior mandible prior to
      implant insertion. The case series included five patients with inadequate bone in
      the posterior mandible for implant placement. The residual ridges were augmented
      with rhBMP-2/ACS and a small amount of bone substitute. Titanium mesh was used to
      protect the graft sites. Dental implants were inserted after 6 months of healing.
      Healing of the grafted ridges was uneventful. Dental implants were placed in all
      grafted sites without the need for further bone augmentation. All 10 implants
      integrated well and were restored with single crowns. The use of rhBMP-2/ACS with
      titanium mesh was effective in this case series for augmentation of the atrophic
      posterior mandible prior to implant placement. This approach offers many
      advantages, including technical ease, no need for bone harvesting, decreased
      morbidity, and reduced surgical time.

PMID- 22140661
TI  - Survival rate of one-piece dental implants placed with a flapless or flap
      protocol--a randomized, controlled study: 12-month results.
AB  - The purpose of this randomized controlled clinical study was to compare the
      survival of a one-piece anodically oxidized surface implant when placed with a
      flapless or flap protocol. Bone loss measurements on radiographs and changes in
      clinical probing depths 1 year post-definitive restoration placement were
      recorded and compared. Fifty-two of 60 patients (implants) remained in the study
      at the 1-year follow-up. At the time of final evaluation, no implant was lost in
      either group. At the time of placement of the definitive restoration, there was a
      mean mesial and distal bone gain in both groups compared to bone levels present
      at the time of implant insertion. There were no significant changes in bone
      levels between placement of the definitive restoration and those recorded 12
      months later, and no significant differences in bone levels between the flap or
      flapless group at 6 or 12 months were noted. No significant differences were seen
      either in pocket depth or change in pocket depth at 6 and 12 months in the
      flapless and flap groups. It was therefore concluded that one-piece anodically
      oxidized surface implants, 1 year post-definitive restoration insertion, had high
      survival rates (100%) and stable marginal bone and probing depth levels whether a
      flapless or flap protocol was used for implant insertion.

PMID- 22140662
TI  - Esthetic evaluation of root coverage outcomes: a case series study.
AB  - The aim of this study was to conduct a 1-year full esthetic evaluation of the
      treatment outcomes of gingival recession using the root coverage esthetic score
      (RES) system. One hundred patients with 195 single or multiple recessions were
      treated using different techniques. One year after surgery, the clinical outcomes
      were evaluated. Only 21 of 195 (11%) treated recessions obtained the maximum RES
      score (10), while 68 recessions (35%) showing complete root coverage obtained
      lower scores. Both single and multiple recessions treated with a coronally
      advanced flap with or without connective tissue grafting achieved similar RES
      scores. Free gingival grafts showed the lowest score.

PMID- 22140663
TI  - Guided bone regeneration around single-tooth implants in the esthetic zone: a
      case series.
AB  - The objective of this case series was to evaluate the clinical and histologic
      outcome of guided bone regeneration around simultaneously placed implants in
      sites with missing buccal bone walls. Eight weeks after tooth extraction,
      implants were inserted, and the sites were augmented in both the horizontal and
      vertical dimensions using a mineralized collagen bone substitute and a
      nonresorbable titanium-reinforced membrane. Six months later, small hard tissue
      biopsy specimens were harvested from the buccal bone walls at approximately mid
      height of the original defect. The histologies revealed ongoing bone formation.
      Clinically, an adequate amount of hard and soft tissue volume had formed.

PMID- 22140664
TI  - Coronally advanced flap associated with a connective tissue graft for the
      treatment of multiple recession defects in mandibular posterior teeth.
AB  - The coronally advanced flap has been documented as an effective surgical
      technique for the treatment of gingival recessions in cases of multiple adjacent
      recession defects, obtaining stable long-term results after 5 years of follow-up.
      The aim of the present study was to test the coronally advanced flap, in
      association with a connective tissue graft, in a case series of 10 patients
      presenting at least two gingival recessions on adjacent teeth in the posterior
      mandibular area. Periodontal parameters were recorded on teeth involved in the
      surgeries at baseline and 1 year. A total of 26 recessions were treated. No
      significant complication affected the surgeries, and no patient abandoned the
      study. Recession depth was reduced from 3.40 +/- 0.83 mm at baseline to 0.28 +/-
      0.32 mm at the 1-year control, while differences in pocket depth were not
      significant. Keratinized tissue increased from 0.57 +/- 0.46 mm to 3.05 +/- 0.71
      mm. Greater reductions in recession depth were observed in cases where the
      initial conditions were worse. A mean 91.2% +/- 4.1% recession coverage was
      obtained. The coronally advanced flap in association with a connective tissue
      graft can be proposed as a valid therapeutic approach for multiple recession
      defects in mandibular posterior areas.

PMID- 22140665
TI  - Fractal analysis: a novel method to assess roughness organization of implant
      surface topography.
AB  - Surface roughness is important for implant osseointegration. It has mostly been
      assessed by amplitude and height descriptors. Fractal analysis is derived from
      fractal geometry and is used to describe the organization of objects found in
      nature, quantifying their shape complexity with a value. Fractal dimension (Df?)
      is an index of the space-filling properties of an object and can be used as a
      parameter that describes the organization of surface roughness. The greater the
      Df value, the more chaotic the surface topography. The aim of this study was to
      assess the Df of implants with three different surface topographies to evaluate
      whether a novel method to measure roughness of implant surface topography could
      be developed. Forty-five disk-shaped samples (10 x 2 mm) with three different
      surface topographies were analyzed by scanning electron microscopy: group A,
      machined surface; group B, sandblasted and acid-etched surface; and group C,
      sandblasted, acid-etched, and neutralized surface. Images at 20,000x and 50,000x
      magnification were processed for quantitative analysis of Df using the box
      counting method. Df values were correlated to the image magnification. At 20,000x
      magnification, Df for groups A, B, and C was 1.81, 1.67, and 1.59, respectively.
      At 50,000x magnification, Df was lower for all examined groups; more
      specifically, Df was 1.77, 1.59, and 1.42 for groups A, B, and C, respectively.
      Statistically significant differences were found between groups A and C at both
      magnifications. Df is used widely and successfully as a measurement to
      characterize anatomical structures and physiologic and pathologic processes. Df
      not only provides an index of roughness size values, but also a measure of
      roughness spatial organization; therefore, it could be a promising method to
      differentiate between rough surfaces capable of supporting osseointegration.

PMID- 22140666
TI  - Comparison of modified widman and coronally advanced flap surgery combined with
      Co2 laser root irradiation in periodontal therapy: a 15-year follow-up.
AB  - The aim of this study was to compare modified Widman flap surgery (MW) to
      coronally advanced flap surgery combined with carbon dioxide laser root
      conditioning (CAF + CO2) from baseline to 15 years of follow-up. Each of 25
      patients participating in this study were treated using a split-mouth design: In
      one quadrant, the teeth received MW surgery (control), and on the other side,
      after a full-thickness flap was raised, a CO2 laser was used and the full
      thickness flap was repositioned coronally and sutured (CAF + CO2, test). Plaque
      Index, Gingival Index, probing depth, and clinical attachment level were
      monitored from baseline to 15 years. For probing depths ? 7 mm, CAF + CO2 sites
      provided greater pocket reduction (P < .01), and data on clinical attachment
      level showed a significant difference between control and test sites at 5 to 6 mm
      (P < .001) and ? 7 mm (P < .001). This study showed that CAF + CO2 therapy
      resulted in significantly higher improvements than MW surgery.

PMID- 22140667
TI  - Minimally invasive treatment of maxillary anterior gingival recession defects by
      vestibular incision subperiosteal tunnel access and platelet-derived growth
      factor BB.
AB  - An array of therapeutic options are available for treatment of gingival recession
      defects, though many of these are better suited for treatment of isolated
      defects. Some of the limitations of current techniques include the need for
      harvesting of autogenous donor tissues and their associated morbidity, as well as
      scar formation at the recipient site resulting from surface incisions. Moreover,
      muscle pull during healing often leads to incomplete root coverage or relapse of
      the recession. The current case reports introduce a novel, minimally invasive
      approach applicable for both isolated recession defects as well as multiple
      contiguous defects in the maxillary anterior region. Access to the surgical site
      is obtained by means of an approach referred to as vestibular incision
      subperiosteal tunnel access (VISTA). This entails making an access incision in
      the maxillary anterior frenum, followed by elevation of a subperiosteal tunnel.
      VISTA allows for both access as well as an opportunity to coronally reposition
      the gingival margins of all involved teeth. In this approach, recombinant human
      platelet-derived growth factor BB saturated onto a matrix of beta-tricalcium
      phosphate is introduced using VISTA over root dehiscences to enhance periodontal
      healing. A novel method of stabilization of the gingival margins is also
      introduced, referred to as coronally anchored suturing, designed to maintain the
      coronal positioning during healing. The current report describes the technique
      and two clinical case documentations for treatment of Miller Class I and II
      defects, demonstrating stable, long-term outcomes. Although VISTA has been
      applied in other regions, its application is most advantageous in the esthetic
      zone.

PMID- 22140668
TI  - Root analog zirconia implants: true anatomical design for molar replacement--a
      case report.
AB  - Replacement of lost teeth using oral implants is an accepted treatment modality
      with well-documented high long-term success rates. Conventional screw- or
      threaded cylinder-type implants have been used almost exclusively. Their
      incongruence with the extraction socket necessitates the use of a barrier
      membrane or bone augmentation to prevent down-growth of connective tissue or
      epithelium between the implant and socket. Although some minor changes in implant
      design have been made, the neck and abutment connection areas have not changed
      much in the past 30 years. Custom-made root analog implants have been employed
      clinically in rare instances; however, they yielded failure rates of up to 96% at
      1 year of follow-up. So far, ovoid implants are the closest in design regarding
      resemblance to the natural tooth anatomy. Root analog zirconia implants with
      macroretentions were developed and produced for immediate single-stage
      replacement of missing or hopeless teeth. This article discusses the treatment
      and 3-year follow-up of a patient with such an implant for replacement of a
      maxillary molar.

PMID- 22140669
TI  - The effects of enamel matrix derivative and cyclic mechanical strain on human
      gingival fibroblasts in an in vitro defect healing model.
AB  - Gingival fibroblasts (GFs) play a considerable role in the maintenance of the
      gingival apparatus as well as in connective tissue repair. Mobility of a
      periodontal wound or soft tissue graft can impair connective tissue healing from
      the GFs. Enamel matrix derivative (EMD) is an enamel matrix protein used
      clinically for periodontal regeneration of intrabony defects and furcations, as
      well as treatment of gingival margin recessions. The goal of this project was to
      compare the effects of varying concentrations of EMD, with and without cyclic
      mechanical strain, on cellular wound fill of human GFs using an in vitro defect
      healing model. GFs were seeded and cultured in six-well flexible-bottomed plates.
      A 3-mm wound was created in the central portion of each confluent well. Three
      wells were treated with each EMD concentration of 0 MUg/mL (control), 30 MUg/mL,
      60 MUg/mL, or 120 MUg/mL. The plates were placed in an incubator containing a
      strain unit to subject test plates to cyclic strain. An identical set of control
      plates were not flexed. Cells were examined on days 4, 8, 12, and 16.
      Microphotographs were taken and wound fill measurements made using image analysis
      software. The percent wound fill was calculated. All nonflexed plates, regardless
      of EMD concentration, reached > 90% defect fill at similar rates by day 16.
      However, in the flexed plates, EMD had a significant negative effect on defect
      fill. The defect fill was 55.7% for 0 MUg/mL EMD, 48.2% for 30 MUg/mL EMD, 36.7%
      for 60 MUg/mL EMD, and 34.1% for 120 MUg/mL EMD on day 16 for the flexed GFs.
      EMD, in concentrations as high as 120 MUg/mL, did not significantly affect the
      amount of defect fill with nonflexed GFs. However, when the GFs were flexed, the
      addition of EMD had a significant negative effect on defect fill in a dose
      dependent manner.

PMID- 22140670
TI  - Implant repositioning by segmental osteotomy: a case series and review.
AB  - Although every effort is made to place dental implants in a proper position, the
      restorative dentist does not always succeed. Historically, treatment options for
      poorly placed implants included removing the implant or leaving it "sleeping."
      Recent modifications of an existing technique, the segmental osteotomy, may offer
      hope in these situations by rendering many of these "hopeless" implants
      salvageable. This paper presents lessons learned from a series of cases in which
      segmental osteotomies were performed to improve the esthetic outcome of implant
      malpositioning. Two clinical cases (one successful, one failed) utilizing
      segmental osteotomy to surgically correct malposed implants are presented with a
      review of the literature associated with the technique. With adherence to proper
      case selection and detailed surgical protocol, segmental osteotomy is a viable
      treatment option to correct misaligned dental implants.

PMID- 22140671
TI  - Microbiologic evaluation of compromised periodontal sites before and after
      immediate intrasocket implant placement.
AB  - This study aimed to elucidate the changes in subgingival microflora before the
      extraction of severely periodontally involved teeth and 1 year after immediate
      implant placement and provisionalization without flap elevation. Clinical
      parameters were recorded for 20 maxillary anterior teeth from 10 individuals
      before and after implant treatment. The clinically observed improvement in the
      soft tissues was found to be compatible with a less pathogenic flora.
      Concentrations of periodontopathogens in the periodontal sites were heavily
      reduced when transformed into peri-implant sites, whereas the relevant counts of
      the beneficial microorganisms were increased.

PMID- 22140672
TI  - Alveolar buccal bone maintenance after immediate implantation with a surgical
      flap approach: a study in dogs.
AB  - This study evaluated buccal bone maintenance after implantation with a surgical
      flap approach immediately following tooth extraction in a dog model. Mandibular
      premolars of six dogs were extracted, and threaded implants of 4-mm diameter and
      8-mm length with as-machined and dual acid-etched surfaces were placed through
      balanced procedures in the distal root extraction sockets with a full-thickness
      flap design. Submerged healing was allowed for 4 weeks, and following
      euthanization, bone-to-implant contact and buccal and lingual bone loss were
      evaluated. None of the parameters evaluated were indicative of an effect of
      implant surface in hindering bone loss around immediately placed implants.

PMID- 22140673
TI  - Interdental papillary house: a new concept and guide for clinicians.
AB  - Surgical and nonsurgical techniques have been proposed to regenerate interdental
      papillae. The results are influenced by the morphology of the interdental space,
      which is the housing for the papilla. The concept of the interdental papillary
      "house" has been established not only to allow diagnosis of the causes of
      papillary loss, but also to manage and predict reconstruction of the interdental
      gingival tissue. The adjacent teeth in contact, involving the proximal contact,
      contour and shape of the teeth, course of the cementoenamel junction, interdental
      distance, and underlying bone crest, determine the outline of the house. Since
      the components are combined, an understanding of each allows adequate treatment
      planning involving interdisciplinary procedures. This new concept serves as a
      guide and teaching aid for the practitioner.

PMID- 22140674
TI  - The ability of human periodontium-derived stem cells to regenerate periodontal
      tissues: a preliminary in vivo investigation.
AB  - Periodontium-derived stem cells (pdSCs) can be cultured as dentospheres and
      differentiated into various cells of the neuronal lineage such as glial cells,
      thereby demonstrating their stem cell state. This study investigated whether
      pdSCs could be differentiated into the osteogenic lineage and, if so, whether
      these cells are able to regenerate periodontal tissue in vivo in an athymic rat
      model. Human adult pdSCs were isolated during minimally invasive periodontal
      surgery and expanded in vitro. To induce osteogenic differentiation, expanded
      pdSCs were cultured for 3 weeks in osteogenic differentiation media. Staining for
      alkaline phosphatase expression was positive, suggesting osteogenic
      differentiation. For in vivo studies, pdSCs were delivered onto suitable collagen
      sponges and implanted into periodontal defects on the right buccal cortex of the
      mandible in 16 immunodeficient nude rats. Histologic analysis of samples from the
      test side revealed reformation of periodontal ligament-like tissue, collagen
      fibers, and elements of bone, but no functional periodontal tissue regeneration.
      The data show that human adult pdSCs are capable of regenerating elements of bone
      and collagen fibers in an in vivo animal model.

PMID- 22140675
TI  - Ultrasensitive detection of phenolic compounds based on a spin-labeled
      luminescent lanthanide complex.
AB  - Herein we propose a novel method for ultrasensitive detection of phenolic
      compounds. This method was developed based on a spin-labeled terbium complex
      Tb(3+)/cs124-DTPA-TEMPO (1). This spin-labeled terbium complex is a weakly
      luminescent compound and shows strong off-on luminescent response to phenolic
      compounds in the presence of horseradish peroxidase (HRP), glutathione (GSH) and
      hydrogen peroxide. The analyte recognition and signaling mechanism are discussed
      and the factors affecting the off-on luminescence have been explored. Detection
      limits of 1.1 nM for phenol, 1.1 nM for resorcine, 0.6 nM for m-cresol, 3 nM for
      p-cresol, and 0.5 nM for 2,4-dichlorophenol were obtained, respectively. The
      practicability of the proposed method has been tested in detection of the
      concentration of spiked nearshore seawaters, and recoveries of 77.4-80.4% with
      relative standard deviations (RSDs) of 1.0-2.2% were obtained.

PMID- 22140676
TI  - All-solid-state potassium-selective electrode using graphene as the solid
      contact.
AB  - Graphene sheets are used for the first time to fabricate a new type of solid
      contact ion-selective electrode (SC-ISE) as the intermediate layer between an
      ionophore-doped solvent polymeric membrane and a glassy carbon electrode. The new
      transducing layer was characterized by transmission electron microscopy, scanning
      electron microscopy, cyclic voltammetry and electrochemical impedance
      spectroscopy. The performance of the new K(+-)selective electrodes was examined
      by a potentiometric water layer test, potentiometric measurements, and current
      reversal chronopotentiometry. The obtained potentiometric sensors were
      characterized with a calibration line of slope close to Nernstian (59.2
      mV/decade) within the activity from 10(-4.5) to 0.1 M. The high capacitance of
      the graphene solid contacts results in a signal that is stable over one week. The
      short response time is less than 10 s for activities higher than 10(-5) M. The
      potential drift of the electrodes was calculated from the slope of the curves at
      longer times (DeltaE/Deltat = 1.2 * 10(-5) V s(-1) (I = 1 nA) and DeltaE/Deltat =
      5.5 * 10(-5) V s(-1) (I = 5 nA)). All the results indicate that graphene is a
      promising material for use as a transducer layer for SC-ISEs.

PMID- 22140677
TI  - Effect of hydrophilicity of room temperature ionic liquids on the electrochemical
      and electrocatalytic behaviour of choline oxidase.
AB  - In the present report, six different nano-composites contaning the same amine
      functionalized multi-walled carbon nanotubes (NH(2)-MWCNTs) but different room
      temperature ionic liquids (RTILs) were prepared. Then, the efficiency of these
      nano-composites as supporting materials for studying the electrochemistry and
      electrocatalysis of choline oxidase (ChOx) as a model enzyme were compared. The
      corresponding cyclic voltammetric and amperometric data showed that the
      electrocatalytic activity and the electroanalytical performance of immobilized
      ChOx depends on the degree of hydrophilicity of RTILs used in the applied nano
      composite. The higher stability (180 days), higher enzyme loading (6.56 mol cm(
      2)), lower detection limit (3.85 MUM) and wider linear range (0.005-0.8 mM) was
      obtained for the most hydrophilic RTIL (1-allyl-3-methylimidazolium bromide).

PMID- 22140678
TI  - ZnO nanorod array polydimethylsiloxane composite solid phase micro-extraction
      fiber coating: fabrication and extraction capability.
AB  - ZnO nanorod array coating is a novel kind of solid-phase microextraction (SPME)
      fiber coating which shows good extraction capability due to the nanostructure. To
      prepare the composite coating is a good way to improve the extraction capability.
      In this paper, the ZnO nanorod array polydimethylsiloxane (PDMS) composite SPME
      fiber coating has been prepared and its extraction capability for volatile
      organic compounds (VOCs) has been studied by headspace sampling the typical
      volatile mixed standard solution of benzene, toluene, ethylbenzene and xylene
      (BTEX). Improved detection limit and good linear ranges have been achieved for
      this composite SPME fiber coating. Also, it is found that the composite SPME
      fiber coating shows good extraction selectivity to the VOCs with alkane radicals.

PMID- 22140679
TI  - Detection of avian influenza virus based on magnetic silica nanoparticles
      resonance light scattering system.
AB  - A highly sensitive method for the detection of avian influenza virus (AIV)
      antigen by the resonance light scattering (RLS) technique has been developed in
      this paper. Magnetic silica nanoparticles (MNs) were modified with AIV antibody
      via covalent binding firstly, the MNs/AIV antibody-AIV antigen immunocomplex was
      formed after the addition of AIV antigen, which can increase the RLS signal at
      545 nm. Under the optimized conditions, the enhanced intensities of RLS at 545 nm
      (DeltaI(RLS)) were proportional to the concentrations of AIV antigen in the range
      of 0.5-50 ng mL(-1), with a detection limit of 0.15 ng mL(-1) and correlation
      coefficient of 0.995. This method was applied to the analysis of AIV antigen in
      spiked chicken serum samples and saliva samples with satisfactory results.

PMID- 22140680
TI  - Regio selective functionalisation of gold nanoparticles with DNA.
AB  - Suspensions of electrocatalytic gold nanoparticles with radii as small as 83 +/-
      13 nm that are functionalised with DNA only in one region have been created using
      templated electrodeposition. The integrity of the bound DNA following
      nanoparticle desorption from the electrode is demonstrated by detecting picomolar
      concentrations of DNA without the need for molecular, e.g., PCR or NASBA,
      amplification.

PMID- 22141109
TI  - Did a local clean indoor air policy increase alcohol-related crime around bars
      and restaurants?
AB  - OBJECTIVE: To evaluate whether the adoption of a local clean indoor air (CIA)
      policy in St. Paul, Minnesota, was associated with changes in alcohol-related
      crimes outside on-premises alcohol-licensed businesses. DESIGN: The enactment of
      a comprehensive CIA policy on 31 March 2006 was used as the intervention time
      point in an interrupted time-series analysis to assess changes in weekly crime
      frequency prior to the policy enactment compared with the period after the policy
      was established (n=261 weeks). SETTING: St. Paul, Minnesota, USA. SUBJECTS: On
      premise alcohol-licensed business addresses were collected from St. Paul,
      Minnesota, for the period of January 2003 to December 2007, and geocoded. A 500
      foot (152.4 m) buffer was drawn around each business. MAIN OUTCOME MEASURES:
      Alcohol-related crime (ie, arrest) data were obtained from the St. Paul Police
      Department; crimes had been geocoded by the police department. They were
      aggregated by week to include only those crimes that occurred within the drawn
      buffer. Relevant types of crimes included serious (eg, aggravated assaults,
      homicide, robbery, rape and theft) and less serious (eg, lesser assault,
      fighting, noise violations, public drunkenness/lewdness or other liquor law
      violations) crimes. RESULTS: Within a buffer of 500 foot of alcohol-licensed
      businesses, 23 978 serious alcohol-related crimes and 49 560 less serious alcohol
      related crimes occurred over 5 years. Using interrupted time-series analyses to
      compare the weekly alcohol-related crime frequency in proximity with the bars and
      restaurants, we found no significant change in either type of crime associated
      with the local comprehensive CIA policy (p=0.13) after adjustment for seasonal
      differences and overall crime frequencies. CONCLUSIONS: Evidence from this study
      suggests that alcohol-related crimes were not significantly affected by a local
      comprehensive CIA policy that banned smoking in public workplaces in St. Paul,
      Minnesota.

PMID- 22141110
TI  - Tuberculous meningitis: barriers to adherence in home treatment of children and
      caretaker perceptions.
AB  - INTRODUCTION: In-hospital treatment of children with tuberculous meningitis (TBM)
      is not a feasible option in many resource-poor countries. Home-based treatment
      has shown to be a viable alternative. Adherence is an important factor
      determining success of treatment. OBJECTIVE: Identify possible barriers to
      adherence of home-based treatment and caretaker perception of the disease.
      METHOD: A qualitative study consisting of 11 in-depth semi-structured interviews
      was performed based on principles of the health belief model. RESULTS: Barriers
      of adherence identified include poor understanding of the disease and
      transmission route, difficulty with medication administration and side effects,
      lack of access to the health-care facility, long waiting times and hidden costs
      of transportation. Caretakers showed good appreciation of the adverse effects of
      noncompliance and benefits obtained from taking treatment in the home
      environment. CONCLUSION: Improved doctor-patient communication, information
      brochures, structural changes to hospital settings, provision of financial and
      peer support all contribute to optimal TBM home-based treatment.

PMID- 22141111
TI  - Porcine abortion due to infection with Actinomyces hyovaginalis.

PMID- 22141112
TI  - Evaluation of spinosad for the oral treatment and control of flea infestations on
      dogs in Europe.
AB  - The novel ectoparasiticide spinosad is a naturally occurring mixture of spinosyns
      A and D formed during a fermentation process. The spinosyns are tetracyclic
      macrolides with a unique ring system. Their mode of action differs from that of
      other commercially available insecticides. Laboratory and field trials were
      conducted to evaluate the use of spinosad in a chewable tablet at a dose range of
      45 to 70 mg/kg for the treatment and control of flea infestations on dogs in
      Europe. Laboratory studies with artificially infested dogs confirmed persistent
      activity against Ctenocephalides felis of higher than 99 per cent at three weeks
      post-treatment with values of 96.5 to 97.8 per cent at four weeks. Two
      multicentric field trials with naturally infected client-owned animals in five
      European countries used selamectin as comparator. Monthly doses were given during
      the summer when many homes were heavily infested. Households with spinosad
      treated dogs showed cumulative benefits with flea burdens reduced by about 97 per
      cent at 14 and 30 days and by 99.6 per cent at 60 and 90 days. Corresponding
      figures for selamectin were significantly lower (P<0.05) at all time points:
      between 88.5 and 91 per cent at 14 and 30 days, then 97.8 and 98.2 per cent at 60
      and 90 days. Thus, the performance of spinosad compared favourably with that of
      the established reference product.

PMID- 22141113
TI  - Association of urinary cadmium excretion with feline hypertension.
AB  - Fifty client-owned senior cats (32 normotensive and 18 hypertensive) with renal
      function ranging from normal to moderately reduced were recruited into a
      prospective cross-sectional study exploring the association of urinary cadmium
      excretion and hypertension in cats. Heparinised plasma samples were collected and
      analysed for routine biochemical parameters. Urine samples were collected via
      cystocentesis and were analysed for cadmium concentrations using inductively
      coupled plasma mass spectrometry (ICP-MS). Blood pressure was measured using the
      Doppler method. Urinary cadmium concentrations were indexed to urinary
      creatinineconcentration. Comparison of urinary cadmium excretion was made between
      hypertensive and normotensive cats.The median (range) urinary cadmium
      concentration standardised to urinary creatinine concentration (UCdCr) in the
      normotensive and hypertensive cats was 0.08 (0.02 to 0.37) and 0.12 (0.02 to
      1.38) nmol/mmol creatinine. The UCdCr was significantly higher in hypertensive
      compared with normotensive cats (P=0.016). UCdCr and plasma creatinine
      concentration remained independent predictors of hypertensive status in a
      logistic regression model. UCdCr and plasma creatinine concentration were not
      correlated (r=-0.01, P=0.956). These data suggest cadmium exposure and
      accumulation in cats may play a role in the development of feline hypertension.

PMID- 22141114
TI  - Lameness scoring system for dairy cows using force plates and artificial
      intelligence.
AB  - Lameness scoring is a routine procedure in dairy industry to screen the herds for
      new cases of lameness. Subjective lameness scoring, which is the most popular
      lameness detection and screening method in dairy herds, has several limitations.
      They include low intra-observer and inter-observer agreement and the discrete
      nature of the scores which limits its usage in monitoring the lameness. The aim
      of this study is to develop an automated lameness scoring system comparable with
      conventional subjective lameness scoring by means of artificial neural networks.
      The system is composed of four balanced force plates installed in a hoof-trimming
      box. A group of 105 dairy cows was used for the study. Twenty-three features
      extracted from ground reaction force (GRF) data were used in a computer training
      process which was performed on 60 per cent of the data. The remaining 40 per cent
      of the data were used to test the trained system. Repeatability of the lameness
      scoring system was determined by GRF samples from 25 cows, captured at two
      different times from the same animals. The mean sd was 0.31 and the mean
      coefficient of variation was 14.55 per cent, which represents a high
      repeatability in comparison with subjective vision-based scoring methods.
      Although the highest sensitivity and specificity values were seen in locomotion
      score groups 1 and 4, the automatic lameness system was both sensitive and
      specific in all groups. The sensitivity and specificity were higher than 72 per
      cent in locomotion score groups 1 to 4, and it was 100 per cent specific and 50
      per cent sensitive for group 5.

PMID- 22141115
TI  - Antimicrobial sales rise in 2010.

PMID- 22141116
TI  - EFRACom seeks details of measures to protect UK egg producers.

PMID- 22141117
TI  - TB sticker scheme for cattle passports in Wales.

PMID- 22141120
TI  - Disciplinary case dismissed.

PMID- 22141123
TI  - New partnership to develop network for companion animal disease surveillance.

PMID- 22141124
TI  - Treatment options for contagious ovine digital dermatitis.

PMID- 22141125
TI  - Organic farming: which side of the hedge?

PMID- 22141126
TI  - Tackling welfare issues in cattle.

PMID- 22141127
TI  - Implications of fitting monitoring devices to wild animals.

PMID- 22141128
TI  - Aspergillosis in gamebirds and ducks.

PMID- 22141129
TI  - Mycotic dermatitis in a vagrant parti-coloured bat (Vespertilio murinus) in Great
      Britain.

PMID- 22141138
TI  - Missed chances: primary care practitioners' opportunity to identify, treat and
      refer adolescents with mental disorders.
AB  - BACKGROUND: Few adolescents with mental disorders consult mental health
      professionals or informal care providers, but many visit primary health care
      services. Primary care practitioners (PCP) have then the opportunity to identify
      and refer these adolescents to specialist services. METHODS: The Israel Survey of
      Mental Health among Adolescents conducted in 2004-2005 interviewed 957
      adolescents and their mothers using the Development and Well-Being Assessment
      (DAWBA) diagnostic inventory and questions related to mental health and primary
      health care service use. Response rate in the located sample was 80%. RESULTS:
      Nearly 70% of adolescents had visited a PCP, more among adolescents with mental
      disorders and among those belonging to the Jewish majority group. Among
      adolescents with mental disorders whose mothers did not consult any mental health
      specialist, 76.5% visited a PCP. CONCLUSIONS: Over 75% of adolescents with a
      mental disorder, who did not seek help from any mental health service provider in
      the past 12 months, visited a PCP in that period. The PCP's potential to
      identify, treat or refer untreated adolescents in need of mental care to
      specialized services is discussed.

PMID- 22141136
TI  - Mechanisms of AXL overexpression and function in Imatinib-resistant chronic
      myeloid leukemia cells.
AB  - AXL is a receptor tyrosine kinase of the TAM family, the function of which is
      poorly understood. We previously identified AXL overexpression in Imatinib (IM)
      resistant CML cell lines and patients. The present study was conducted to
      investigate the role of AXL and the mechanisms underlying AXL overexpression in
      Tyrosine Kinase Inhibitor (TKI)-resistant CML cells. We present evidence that
      high AXL expression level is a feature of TKI-resistant CML cells and knockdown
      of AXL sensitized TKI-resistant cells to IM. In addition, expression of wild-type
      AXL but not a dominant negative form of AXL confers IM-sensitive CML cells the
      capacity to resist IM effect. AXL overexpression required PKCalpha and beta and
      constitutive activation of ERK1/2. Accordingly, GF109203X a PKC inhibitor, U0126
      a MEK1 inhibitor and PKCalpha/beta knockdown restore sensitivity to IM while
      PKCalpha or PKCbeta overexpression in CML cells promotes protection against IM
      induced cell death. Finally, using luciferase promoter activity assays we
      established that AXL is regulated transcriptionally through the AP1 transcription
      factor. Our findings reveal an unexpected role of AXL in resistance to TKI in CML
      cells, identify the molecular mechanisms involved in its overexpression and
      support the notion that AXL is a new marker of resistance to TKI in CML.

PMID- 22141140
TI  - Psychosomatic symptoms among hospital physicians during the Gaza War: a repeated
      cross-sectional study.
AB  - Research regarding psychosomatic symptoms among  hospital physicians during armed
      conflict is scarce. The  current study compared psychosomatic symptoms  of
      exposed and unexposed hospital physicians in two  studies. The studies were
      conducted during 2009 and  included a survey of two random samples of hospital 
      physicians, one conducted during the Gaza War and  the other conducted six months
      later. Each sample  included hospital physicians who were directly exposed  to
      war related stress and others who were not (Study  1: N = 54; Study 2: N = 31).
      In Study 1, exposed hospital  physicians did not differ from unexposed physicians
      in the level of psychosomatic symptoms during the  war (Psychosomatic Problems
      Scale 6.48 vs 4.09).  However, in Study 2, exposed physicians reported a  higher
      level of psychosomatic symptoms (10.33 vs 3.21).  Moreover, analysis of
      covariance revealed a significant  interaction effect of Exposure X Study (F =
      7.976; p =  .006; ?p2 = .100). Exposure to war-related stress takes  a toll on
      psychosomatic symptoms among hospital  physicians. This late onset of
      psychosomatic symptoms  is discussed in light of the cognitive-energetical model.

PMID- 22141139
TI  - Posttraumatic stress disorder in  former 'comfort women'.
AB  - OBJECTIVE: This study investigated the mental health of former 'comfort women'
      who serviced the Japanese Imperial Military during the Second World War. METHOD:
      We evaluated 26 former comfort women's life histories, cognitive functioning, DSM
      IV diagnosis of posttraumatic stress disorder (PTSD), depression, paranoid state,
      anger, and Rorschach test results, and compared the data with those of 24 healthy
      women. RESULTS: Cognitive functioning was not significantly different between
      former comfort women and the comparison group. All 26 former comfort women had
      undergone traumatic experiences such as sexual slavery and had suffered PTSD
      symptoms at least once in their lives. Of the 26, 8 (30.8%) were diagnosed as
      having PTSD, as opposed to none in the comparison group. The women's PTSD
      symptoms were characterized by avoidance behavior, intrusive and distressing
      recollections, and anger. There were no significant differences in depression or
      paranoid state between the two groups, but former comfort women had impairments
      in anger control. Former comfort women with PTSD were more depressed. On the
      Rorschach test, former comfort women revealed characteristic responses related
      not only to sex and morbidity but also to anger and violence. LIMITATIONS: The
      small number of subjects might not represent all former comfort women. Some data
      collected by self report might limit the objectivity of the results. CONCLUSIONS:
      The results suggest that former comfort women are still suffering from traumatic
      memories, symptoms of PTSD, including avoidant behavior, and anger control
      impairment, even 60 years after the end of the war.

PMID- 22141141
TI  - Burnout among general hospital mental health  professionals and the salutogenic
      approach.
AB  - Professionals working in mental health often exhibit  high levels of strain
      leading to poor psychological wellbeing,  emotional exhaustion and depletion of
      personal  resources. Even under tight global economic conditions  preventing
      burnout should be given high priority among  mental health providers. This paper
      looks at the wide  spectrum of stressors found in specialists working  in the
      mental health area and examines, with the  salutogenic approach in the
      background, ways to relieve  professional burnout among general hospital mental 
      health providers. Guidelines for managers and staff to  alleviate their
      professional strain are suggested so as  to improve the quality of life in the
      workplace.

PMID- 22141142
TI  - Role of life events in obsessive compulsive disorder.
AB  - BACKGROUND: There are very few studies examining the role of life events in
      obsessive compulsive disorder (OCD). Moreover, these studies have methodological
      limitations and have reported contradictory findings. OBJECTIVE: To examine the
      frequency of life events in patients with OCD as compared to normal healthy
      controls. METHODOLOGY: 10 patients fulfilling ICD-10 DCR criteria of OCD were
      rated with Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Rating Scale
      for Depression (HAM-D) and Presumptive Stressful Life Events Scale (PSLES). A
      group of 10 normal controls were also rated on PSLES. Finally, both groups were
      compared in terms of life events. RESULTS: The frequency of life events, six
      months (t=3.95, p=.001) and lifetime (t=5.53, p less than .001), were
      significantly higher in patient group in comparison to controls. PSLES scores
      showed significant correlation with YBOCS scores. However, there was no
      correlation between PSLES and HDRS scores. Stepwise linear regression analysis
      showed PSLES scores significantly positively predicted obsessive and compulsive
      scores. CONCLUSION: Life events were significantly more frequent in OCD patients
      both six months and lifetime, as compared to healthy controls. The severity of OC
      symptoms was found to be directly proportional to the number of stressful life
      events experienced in the last six months prior to onset.

PMID- 22141143
TI  - Holocaust student tour: the impact on spirituality and health.
AB  - BACKGROUND: 'March of the Living' is a 2-week excursion to Poland and Israel for
      high school students to learn and experience sites of Holocaust destruction.
      METHODS: This study looked at the effect of their experience on spirituality and
      health. The sample consisted of 134 Jewish students, ages 16-19 years. Students
      were assessed initially (before MOTL=time 1) by completing a background survey
      (i.e., demographics, "Jewishness," and Holocaust related information), a World
      Health Organization, Quality of Life-Spirituality, Religion, and Personal beliefs
      field-test instrument, and the Child Somatization Inventory. Surveys were
      repeated end-Poland (time 2) and again (after MOTL=time 3) approximately 3-4
      months after the trip. RESULTS/CONCLUSIONS: Most facets of spirituality
      significantly increased between time 1 and time 2, and varied from time 2 to time
      3, while strength and hope remained elevated. Faith increased from time 1 to time
      2 and was maintained at time 3. Fear of dying rose at time 2, decreasing
      significantly at time 3. A positive correlation between spirituality and
      "Jewishness" was found.

PMID- 22141144
TI  - Pisa syndrome and laryngeal dystonia induced by novel antipsychotics.
AB  - OBJECTIVES: Psychopharmacotherapy with antipsychotics frequently leads to
      different undesirable extrapyramidal side effects. Tardive dystonia is one of
      them and some of its forms can be dangerous. Usually tardive dystonia occurs
      during treatment with typical antipsychotics. The new novel drugs raised great
      expectations, but this adverse event also has been found among patients treated
      with different kinds of atypical antipsychotics. Publications about tardive
      movement disturbances induced by these medications become more and more frequent.
      Our report does not address the management of the patients tardive dystonia but
      only illustrates the phenomenon. METHOD: We describe here three patients
      suffering from chronic schizophrenia treated with second generation
      antipsychotics, who developed dystonic symptoms: one with laryngeal dystonia and
      two others Pisa syndrome. In the patient with laryngeal dystonia these symptoms
      appeared after restarting risperidone treatment, in the other patient after
      diminishing the dosage of risperidone and adding sertindole, and in the third
      patient the syndrome appeared after beginning ziprasidone. CONCLUSIONS: This case
      series suggests that atypical antipsychotics may have a causal relationship in
      the development of different forms of tardive dystonia. Physicians should be
      aware of this problem and always obtain information about the medication used
      prior to the appearance of movement disturbance.

PMID- 22141145
TI  - Psychiatric hospitalization by court observation order in Israel: a ten year
      follow up study.
AB  - OBJECTIVES: To explore the proportion of defendants hospitalized by court
      observation order (COO) who were diagnosed as having a psychiatric disorder
      during: 1) the COO period, or 2) a 10-year follow-up period. METHODS: Data on all
      adult defendants, who underwent psychiatric hospitalization by COO between 1991
      and 1995, were extracted from the National Psychiatric Case Registry of the
      Israel Ministry of Health, and rehospitalizations over the next ten years were
      identified. ANO VA and Wilcoxon signed-rank test were used for comparing the
      diagnosed and undiagnosed defendant cohorts. RESULTS: Only 17% of defendants
      hospitalized by COO received a psychiatric diagnosis (N=316), while the remaining
      referred defendants (N=1,532) were not diagnosed as suffering from any
      psychiatric disorder. Although 56% of the initially undiagnosed group (N=863)
      were rehospitalized and received a psychiatric diagnosis during the next ten
      years, 36% of the original cohort never received a diagnosis subsequent to
      hospitalization (N=556). Significant median differences in inpatient days
      associated with a follow-up diagnosis of psychotic disorder were found between
      the diagnosed and undiagnosed defendant cohorts (z=4.89, p less than .001).
      CONCLUSIONS: The high rate of diagnosis of defendants who were undiagnosed at the
      index hospitalization suggests that the COO is ineffective and tends to discharge
      without diagnosis defendants who are later found to be psychotic. Therefore, an
      independent examination of the accuracy of the forensic psychiatric evaluation
      (FPE) process is called for, to determine whether actual disorders are being
      missed. There should be a professional and public debate on the unnecessary use
      of court-ordered hospitalizations and ways of their prevention.

PMID- 22141146
TI  - Internet-related psychosis-a sign of the times.
AB  - BACKGROUND: The psychopathological implications of the Internet are slowly being
      revealed as its use becomes increasingly common. This papers aim is to call
      attention to computer mediated communication (CMC), such as Facebook or chats,
      and alert to its possible relation to psychosis. DATA: We describe three
      individuals, with no prior major psychiatric disorder, who presented for
      psychiatric treatment, due to psychotic symptoms which appeared de novo while
      they were immersed in CMC. All three patients pointed to the contribution of
      specific CMC features to the gradual emergence of their psychotic symptoms. They
      described a 'hyperpersonal' relationship with a stranger, mistrust of the aims
      and identity of the other party, blurred self boundaries, misinterpretation of
      information, and undesirable personal exposure in cyberspace. The patients had
      little prior experience with computers or the Internet, and their vulnerability
      was intensified due to difficulties in deciphering the meaning of various
      elements of CMC and in managing its technical aspects. CONCLUSIONS: The cases we
      present support the assumption that unique features of CMC might contribute to
      the formation of psychotic experiences. The use of the Internet is vast, and, as
      such, we propose that medical staff members might consider routinely questioning
      patients about their use of it, especially CMC.

PMID- 22141147
TI  - Night eating syndrome among patients with depression.
AB  - OBJECTIVE: The purpose of this study was to identify the rate of night eating
      syndrome (NES) in a depressed population. METHOD: The study sample was composed
      of 162 depressed patients and 172 healthy control participants. RESULTS: The
      rates of night eating in our sample with depression (35.2%) was higher as
      compared with healthy control participants (19.2%) (p less than 0.05). In
      addition, in the depression group, the rate of NES-positive patients did not
      differ in accordance with body mass index (BMI) classification (p more than
      0.05). However, in the control group, the rate of NES-positive patients was
      significantly different with regard to BMI classification, and NES diagnosis was
      highest in the obese members of the control group (p less than 0.05). Multiple
      logistic regression analysis was then used to evaluate the relationships of four
      variables: depression, gender, education status and BMI with the diagnosis of
      NES. Results showed that significant independent predictors of NES were
      depression, gender, and a BMI of 25 or greater. DISCUSSION: This is the first
      study to find that depressed patients are at a significantly greater risk for
      NES. Depression, male gender and BMI may account for the high rate of NES found
      in this population.

PMID- 22141148
TI  - Diagnostic and therapeutic challenges.

PMID- 22141149
TI  - Nobel Prize to immunology.

PMID- 22141150
TI  - Biosignal 2010: Advanced technologies in intensive care and sleep medicine.

PMID- 22141151
TI  - Tuning of the drug delivery vehicle.

PMID- 22141152
TI  - Improving the homogeneity of DNA patterning  on microarrays.

PMID- 22141153
TI  - Targeted nanoparticles for phototherapy.

PMID- 22141154
TI  - Advantages of a positive surface charge.

PMID- 22141155
TI  - Reply to Sharp et al.: Host species sampling bias and Plasmodium falciparum
      origin paradigm shifts.

PMID- 22141156
TI  - A calcium-activated nonspecific cation channel from olfactory receptor neurones
      of the silkmoth Antheraea polyphemus.
AB  - Single-channel patch-clamp techniques were used to identify and characterize a
      Ca2(+)-activated nonspecific cation channel (CAN channel) on insect olfactory
      receptor neurones (ORNs) from antennae of male Antheraea polyphemus. The CAN
      channel was found both in acutely isolated ORNs from developing pupae and in
      membrane vesicles from mature ORNs that presumably originated from inner
      dendritic segments. Amplitude histograms of the CAN single-channel currents
      presented well-defined peaks corresponding to at least four channel substates
      each having a conductance of about 16 pS. Simultaneous gating of the substates
      was achieved by intracellular Ca2(+) with an EC(50) value of about 80 nmol(-l).
      Activity of the CAN channel could be blocked by application of amiloride
      (IC(50)<100 nmoll(-1)). Moreover, in the presence of l MUmoll(-1) Ca2+,opening of
      the CAN channel was totally suppressed by 10 MUmoll(-1) cyclic GMP,whereas ATP (1
      mmoll(-1)) was without effect. We suggest that the CAN channel plays a specific
      role in modulation of cell excitability and in shaping the voltage response of
      ORNs.

PMID- 22141157
TI  - [Gender differences in choice of specialty among Danish medical students].

PMID- 22141158
TI  - [Prioritization is for physicians too].

PMID- 22141159
TI  - [Occupational health physicians prevent diseases].

PMID- 22141160
TI  - The health of children and adolescents in perspective.

PMID- 22141161
TI  - The density of disciplinary knowledge motivated by the natural history of
      valvular heart diseases.

PMID- 22141163
TI  - Re-entry applicants must walk an unfair path.

PMID- 22141162
TI  - Bubbling to the surface--mental health and disaster recovery.

PMID- 22141164
TI  - New English Language Standard a significant concern.

PMID- 22141165
TI  - The health system is a "people system".

PMID- 22141166
TI  - Nursing in the Gulf.

PMID- 22141167
TI  - Long-awaited progress QH payroll debacle.

PMID- 22141168
TI  - Mandatory reporting--your obligations.

PMID- 22141169
TI  - Update on harmonisation of workplace health and safety legislation.

PMID- 22141171
TI  - SmartClinics: a future direction of primary health care.

PMID- 22141170
TI  - Local Health and Hospital Networks: how will they affect Queensland health's
      management of health and safety?

PMID- 22141172
TI  - Growing confidence for a working life.

PMID- 22141173
TI  - War, suffering and modern German history.
AB  - This introduction proceeds in five steps. First, it briefly considers the
      etymology of the term "suffering," as well as the way in which scholars from
      different disciplines have approached it conceptually and empirically. Second,
      drawing on the contributions to this issue, it raises general themes emerging
      from the study of the Thirty Years, Franco-Prussian and First World Wars, with
      particular attention to gender, the disabled, and Jewish-German veterans.
      Finally, it considers the most politically contested field of German suffering -
      the Second World War - and reflects on how that suffering can be narrated and
      understood without running into the intellectual dead ends of either self-pity or
      collective guilt.

PMID- 22141174
TI  - German suffering in the Franco-German War, 1870/71.
AB  - Suffering during the Franco-Prussian War of 1870/71 has to be interpreted in the
      context of three developments: the willingness to alleviate wartime suffering,
      which had led to the foundation of the International Red Cross and the Geneva
      Convention a few years earlier, the industrialization of war, which had
      enormously increased the efficiency of the weaponry, and the nationalization of
      war. For many Germans, the outcome of the war justified the wartime suffering,
      which was often trivialized in the media. The small number of authors who saw the
      high casualty numbers and the pain of the victims as a warning about the
      consequences of modern warfare usually belonged to the anti-Prussian opposition.
      Nationalist euphoria in the face of victory and German unification drowned out
      such critics, whose patriotism was in doubt. Finally, the remembrance of the war
      during the Kaiserreich aimed largely at celebrating the triumph of the German
      army and the foundation of the national state. The glorification of the military
      was hardly compatible with a detailed description of the misery of the
      battlefield and the pain of war victims. In 1870/71 and in the subsequent
      decades, nationalism overwhelmed and eventually excluded a humanitarian
      narrative.

PMID- 22141175
TI  - The German-Jewish soldier: from participant to victim.
AB  - The story of German-Jewish soldiers and veterans of World War I illustrates how,
      under circumstances of inclusion (even if incomplete) rather than vicious
      persecution, Jewish suffering in wartime, and with it the forms of collective
      memory and strategies for commemoration of the dead, could closely parallel, even
      intersect with, the suffering of Germans as a whole. To be sure, the points of
      intersection were accompanied by points of deflection. Even when Jews served,
      fought, suffered and died as German soldiers, their interpretations of the war
      experience, and their communities' postwar memory and commemorative practices,
      differed from those of other Germans. In many ways, however, German-Jewish
      veterans suffered the aftermath of the war as did other Germans; they shared the
      prevailing fury over war guilt and reparations, and they retained a strong pride
      in their military service, a pride through which they interpreted the events of
      1933-1945.

PMID- 22141176
TI  - Land rent and housing policy: a case study of the San Francisco Bay area rental
      housing market.
AB  - In the San Francisco Bay Area, where residential rent is among the highest in the
      United States, an analysis of data from several sources demonstrates that high
      rent cannot be accounted for by higher quality, higher operating costs, or higher
      construction costs. At least one-third of the total rent paid is land rent.
      Despite increases in real incomes, very-low-income tenants in the Bay Area today
      have less income remaining after payment of rent than tenants did in 1960. High
      land rent is a long-term feature of the Bay Area rental market that results
      mostly from its geography, the density of its urban centers, and a strong
      economy, rather than from regulatory barriers to new multifamily construction.
      Deregulation is not a sufficient response to the effects of land rent on low
      income tenants. Government should subsidize non-profit housing organizations,
      particularly land trusts that remove residential land from the market. Taxes on
      land rent would be a particularly appropriate funding source.

PMID- 22141177
TI  - TRAP abortion laws and partisan political party control of state government.
AB  - Targeted Regulation of Abortion Providers (or TRAP) laws impose medically
      unnecessary and burdensome regulations solely on abortion providers in order to
      make abortion services more expensive and difficult to obtain. Using event
      history analysis, this article examines the determinants of the enactment of a
      TRAP law by states over the period 1974-2008. The empirical results find that
      Republican institutional control of a state's legislative/executive branches is
      positively associated with a state enacting a TRAP law, while Democratic
      institutional control is negatively associated with a state enacting a TRAP law.
      The percentage of a state's population that is Catholic, public anti-abortion
      attitudes, state political ideology, and the abortion rate in a state are
      statistically insignificant predictors of a state enacting a TRAP law. The
      empirical results are consistent with the hypothesis that abortion is a
      redistributive issue and not a morality issue.

PMID- 22141179
TI  - Mind-body therapies can improve quality of life.

PMID- 22141178
TI  - Maximizing your benefit from chemotherapy.  Supportive strategies to improve
      quality of life.

PMID- 22141180
TI  - Getting the support you need from those around you.

PMID- 22141181
TI  - The diagnosis of art: scleroderma in Paul Klee - and Rembrandt's scholar?

PMID- 22141182
TI  - The diagnosis of art: WH Auden's face.

PMID- 22141183
TI  - Paul D. Boyer-Nobel prize for work on ATP synthase.

PMID- 22141184
TI  - Developmental variation of the primate dentition: the 2011 AAPA symposium in
      honor of Don Reid.

PMID- 22141185
TI  - General and specialized medicine and psychiatry.

PMID- 22141186
TI  - [Comparative efficacy of original and generic valsartan arterial hypertension].

PMID- 22141187
TI  - Permanent certification program for health information technology; revisions to
      ONC-Approved Accreditor processes. Final rule.
AB  - Under the authority granted to the National Coordinator for Health Information
      Technology by section 3001(c)(5) of the Public Health Service Act (PHSA) as added
      by the Health Information Technology for Economic and Clinical Health (HITECH)
      Act, this final rule establishes a process for addressing instances where the ONC
      Approved Accreditor (ONC-AA) engages in improper conduct or does not perform its
      responsibilities under the permanent certification program. This rule also
      addresses the status of ONC-Authorized Certification Bodies (ONC-ACBs) in
      instances where there may be a change in the accreditation organization serving
      as the ONC-AA and clarifies the responsibilities of the new ONC-AA.

PMID- 22141188
TI  - Primate evolution in Pittsburgh.

PMID- 22141189
TI  - Belgian Society of Cardiology. Belgian Heart Rhythm Association (BeHRA).The 5th
      Belgian Heart Rhythm Meeting, 6-7 October 2011, Brussels. Abstracts.

PMID- 22141190
TI  - Collaborative effects of diet and exercise on cognitive enhancement.
AB  - Certain dietary factors, such as omega-3 fatty acids and curcumin, are reviewed
      in their context of stimulating molecular systems that serve synaptic function,
      while diets rich in saturated fats do the opposite. In turn, exercise, using
      similar mechanisms as healthy diets, displays healing effects on the brain such
      as counteracting the mental decline associated with age and facilitating
      functional recovery resulting from brain injury and disease. Diet and exercise
      are two noninvasive approaches that used together may enhance neural repair.
      Omega 3 fatty acids and curcumin elevate levels of molecules important for
      synaptic plasticity such as brain-derived neurotrophic factor (BDNF), thus
      benefiting normal brain function and recovery events following brain insults.

PMID- 22141191
TI  - Infantile autism: a chronic psychosis since infancy due to synaptic pruning of
      the supplementary motor area.
AB  - The rise in infantile autism, learning problems, cognitive decline with age,
      Alzheimer's, Parkinson's diseases and the SIDS epidemic, has a common cause in
      the rising dietary deficit in Omega-3 brain-food. This paper suggests that aside
      from the wider concept of autism spectrum disorders (ASD) and pervasive
      developmental disorders (PDD), the rise in infantile autism (IA) in the last
      decade is the effect of deficient brain-food (Omega-3). The consequent delay of
      development, prolongs the 2nd regressive event in infancy to pruning of the
      centre in the Medial Frontal Lobe System that connects hippocampus and singulum.
      With a consequently defective supplementary motor area (SMA), the Delayed
      Response Function is affected leading to persistent psychosis. Post-pubertal
      episodic psychoses are associated with acute reduction of excitation, a risk of
      breakdown of circuitry, insufficient fill-in mechanisms, and silent spots. An
      acute psychosis occurs if the silent spots compromise SMA. Only two brain areas
      have continuous neurogenesis, indicating their important functions: the
      Hippocampus and Olfactory Bulb that belongs to the lateral frontal lobe system
      essential to survival. Concerned with necessity of action in response to the
      environment, it relies upon short-term memory and acute feedback mechanisms
      influenced by emotion and motivation from the external world. In contrast, the
      medial frontal lobe network is controlled by feed-forward predictive mechanisms
      related to storage of information The Delayed Response Function is mastered at 7
      months, when 2nd event occurs with pruning of axons and dendrites. An abolished
      or defective delayed response function seriously incapacitates an individual: a
      defective "social brain" with an inability for conscious action and to
      communicate, predominates in IA. There is a near lack of speech, despite normal
      vision and hearing in the minority without marked adversity in pregnancy, at
      delivery or in infancy. The recent rise in IA despite no rise in adversity
      signifies a rising deficiency in brain-food. This is suggested by a changing
      clinical picture: no Mental Retardation in an IA majority. Deficit in olfaction
      is pathognomonic in schizophrenia since 30 yrs and distinguishes the Asperger
      syndrome. If brain-food deficiency alone sufficiently prolongs pruning to cause
      absent activity in SMA in infancy, less mentally retarded IA from other causes
      might be observed. Deficit in brain-food was evident in the Sudden Infant Death
      Syndrome: birthweight averaged 200-300g lower than sibs, Omega-3 levels in
      brainstem were lower than controls. Only 20% SIDS died in first hypoxic episode,
      suggesting such episodes are more frequent than we imagined. Children with
      learning-behaviour problems have similarly depressed birthweight. A general
      deficiency in omega-3 contributes to the lacking reduction in Schizophrenia,
      despite early puberty predominates. Olfactory bulb is first affected in the
      Alzheimer's and Parkinson's disease. Cognitive decline with age, hippocampal
      dysfunctions rises markedly irrespective of disease, but the major mental
      illnesses and Infantile Autism in particular, benefit from "brainfood" that might
      also prevent a development of these disorders. To secure optimal brain function
      in the coming generations, there is a need to change the diet now from its
      emphasis on protein for body growth to food for the brain. This means there is a
      need to increase fish and sea food consumption.

PMID- 22141192
TI  - Consciousness reinstated using the certainty principle--a better mental health
      strategy.
AB  - The statistical probability that six consecutive carbon double-bonds will all be
      'cis' is less than chance (p < 0.02). The chances of all-cis-docosahexaenoic acid
      (DHA) recurring in quantity over geological time is infinitesimal. Since such
      intriguing considerations are scrupulously eliminated from orthodox
      conceptualisations, a refurbished Occam's razor--the Certainty Principle--is
      offered as a responsible pragmatic guide. Six indelible flaws in our ways of
      knowing precedes a psychiatry that is immediately understandable, self-evident
      and effective, here supported by objective evidence from prison data. The only
      realistic antidote to our lethal global psychiatric epidemic is reinstating
      consciousness and its wellbeing.

PMID- 22141193
TI  - Evaluation of nutritional status using body fat, physiological and biochemical
      parameters in some Nigerian women.
AB  - Some nutritional parameters were investigated in 62 healthy Nigerian female
      subjects of low socio-economic status. The percentage body fat (% BF) and some
      biochemical parameters, High and Low Density Lipoprotein Cholesterol (HDL-C and
      LDL-C), Total Plasma Cholesterol (TC), Triglyceride (TG), Uric Acid (UA), Urinary
      Creatinine (U-Cr), Creatinine in plasma (P-Cr) and Creatinine clearance (Cr-CI),
      were evaluated. Also determined were the Body Mass Index (BMI), Packed Cell
      Volume, Systolic and Diastolic Blood Pressure (BP-I, BP-2), various skin-fold
      measurements and body circumferences. Reference values were then established for
      these various parameters and the correlation between the various variables
      determined. When the subjects were stratified into four groups (underweight,
      normal, overweight, and obese) based on their BMI, significant differences
      (ANOVA, p < 0.05) were observed in LDL-C, Cr-CI, BP-I, as well as 10 out of the
      13 anthropometric parameters. These differences could possibly provide
      diagnostic/prognostic insight for the four groups and the many important diseases
      associated with them. The hip circumference, in particular, has such a high
      correlation with both BMI and % BF that it is being suggested as a substitute for
      these two important parameters in Nigerian women of low socio-economic
      background.

PMID- 22141194
TI  - The rise and fall of food minerals.
AB  - Climax fertility developed in early times with higher plants and animals
      developing to use this high standard of mineral nutrition. This climax fertility
      is built on carbon fixed from the air by plants. This carbon provides the energy
      to soil micro-organisms. Both those dependant on soil organic matter and those
      that draw energy and minerals directly from the plant. These micro-organisms
      increase plant mineral content and provide other life compounds. Agricultural
      activity has broken this climax fertility leading to a fall in food chain
      minerals.

PMID- 22141195
TI  - Food nanotechnology: water is the key to lowering the energy density of processed
      foods.
AB  - It is crucial that emergent technologies create foods that help prevent the
      causal mechanisms of the diet induced disease epidemic. Food nanotechnology could
      create modem convenience foods that mimic and improve on the nutritional value of
      the most nutritious cooked wild foods for humans. Structuring a solid processed
      food similar to a celery stalk using self-assembled, water-filled, edible
      nanocells or nanotubes would substantially lower its energy density (<1.6 kcal g(
      1)). Food technologists could harness the natural turgor force to produce a firm
      chocolate bar, biscuit or breakfast cereal with a good bite, without altering the
      appearance or taste of the product. Water carries flavour with few calories, and
      taste sensation per mouthful could be improved by processing food on the
      nanoscale to increase the surface area that is in contact with taste and smell
      receptors. The bioavailable nutrient content (including cofactors) of processed
      foods could be increased by existing bioactive nanoencapsulation. This would
      allow people to continue to consume modern convenience food on a mass scale,
      while simultaneously and significantly increasing nutrient intake and reducing
      energy intake per day. Thus, helping to reduce mental ill health, obesity and
      other postprandial insults.

PMID- 22141196
TI  - Cognitive decline and Alzheimer's disease.

PMID- 22141197
TI  - Nutritional therapy in practice for learning, behavioural and mood disorders.
AB  - There is an evidential link between diet, mood and behaviour, but a shortage of
      formalised educational literature covering the role of nutritional science and
      its application in the care and treatment of mental health problems. In the U.K.,
      a limited amount of a few types of fruit and vegetables, few wholegrains and
      little oily fish are consumed. Instead, large quantities of refined
      carbohydrates, altered fats, intensively reared meat and dairy products are
      eaten, along with unknown combinations of synthetic chemicals and residues. In
      some individuals, specific nutritional and environmental factors generate
      physiological responses which may influence mood, promote anti-social behaviour
      and trigger overwhelming cravings for certain foods or substances. Nutritional
      Therapists are not currently part of the multidisciplinary team assessing people
      suffering from mental health problems. They generally work in private practice
      with clients on an individual basis. Their role is to improve diet and identify
      potential food intolerances, hormone imbalances, blood sugar issues, enzyme
      deficiencies, compromised gut immunity, increased nutrient requirements, a toxic
      metal burden or chemical sensitivities. Each case is examined on its own merits,
      given the variety of genetic and environmental differences among individuals. The
      considerable challenge for the nutritional therapist remains to intervene safely
      and effectively in mental health conditions which involve multiple complex and
      interacting mechanisms.

PMID- 22141198
TI  - Education in clinical chemistry and laboratory medicine in various European
      countries.

PMID- 22141199
TI  - The regulation of clinical chemistry in Slovenia.
AB  - The practice of medical biochemistry in Slovenia includes clinical biochemistry
      (including toxicology, therapeutic drug monitoring, endocrinology, molecular
      diagnostics, immunology), hematology and coagulation. To start the vocational
      medical biochemistry training programme it's necessary to have a completed
      university degree (second cycle) in pharmacy, chemistry, biochemistry, medicine
      or other relevant university study and 1 year supervised practical training in
      medical laboratories, completed with mandatory state exam at Ministry of Health.
      The duration of vocational training programme is 4 years and is completed with
      final exam. The title after passed final examination is Medical biochemistry
      specialist. In October 2005 EC4 (Communities Confederation of Clinical Chemistry
      and Laboratory Medicine) approved Equivalence of standards of Slovenian national
      standards for medical biochemistry specialists. Since 2006 it is mandatory to be
      registered and to have valid license for medical biochemistry specialists and
      other professionals in laboratory medicine with at least university degree
      (second cycle) of education. Laboratory medicine in Slovenia is regulated
      globally through the Law of health-care activity and particularly through the
      Bylaw of laboratory medicine. The latter is based on standard ISO 15189, ratified
      in 2004. The Bylaw envisages granting working license to laboratories, valid for
      5 years period. Granting of working licenses is ongoing process and first
      licenses have been granted in 2009. Important improvement toward the quality
      requirements for medical laboratories can be observed in the last 5 years.
      Parallel with the Bylaw of medical laboratories, Slovenian Accreditation (SA),
      the legal national accreditation body, started the initiative for accreditation
      of medical laboratories according to ISO 15189. It is in the implementation
      phase.

PMID- 22141200
TI  - Education of medical biochemists in Bosnia and Herzegovina.
AB  - In this paper we would like to briefly introduce readers to the situation in the
      field of laboratory medicine in Bosnia and Herzegovina, with a focus on training
      in the field of medical biochemistry. As in some of neighboring countries, term
      Medical biochemist is the usual name for the Clinical biochemist or Clinical
      chemist in Bosnia and Herzegovina. Despite the difficult period through which the
      profession had passed in the last two decades, laboratory work, particularly
      clinical biochemistry, has managed to retain the necessary quality and keep pace
      with the developed world. In post war period, Society of Medical Biochemists of
      Bosnia and Herzegovina held regular meetings each year as a part of "life long
      learning" process, where both scientific and vocational lecturers presented their
      work. A single law on the state level would provide us with more defined and
      precise answers, such as: who can get a specialization, how long should last the
      training for medical biochemistry specialists (duration in years). This law
      should be in consent with the program described in EC4 or other documents given
      by the EFCC (European Federation of Clinical Chemistry and Laboratory Medicine)
      and IFCC (International Federation of Clinical Chemistry and Laboratory
      Medicine).

PMID- 22141201
TI  - Clinical chemistry and laboratory medicine in Croatia: regulation of the
      profession.
AB  - Heterogeneity exists across Europe in the definition of the profession of
      clinical chemistry and laboratory medicine and also in academic background of
      specialists in this discipline. This article provides an overview of the
      standards of education and training of laboratory professionals and quality
      regulations in Croatia. Clinical chemistry in Croatia is almost exclusively
      practiced by medical biochemists. Although term Medical biochemist often relates
      to medical doctors in other European countries, in Croatia medical biochemists
      are not medical doctors, but university degree professionals who are qualified
      scientifically. Practicing the medical biochemistry is regulated by The Health
      Care Law, The Law of the Medical Biochemistry Profession and The Law of the State
      and Private Health Insurance. According to the law, only medical biochemists are
      entitled to run and work in the medical biochemistry laboratory. University
      degree is earned after the 5 years of the studies. Register for medical
      biochemists is kept by the Croatian Chamber of Medical Biochemists. Licensing is
      mandatory, valid for 6 years and regulated by the government (Law on the Health
      Care, 1993). Vocational training for medical biochemists lasts 44 months and is
      regulated by the national regulatory document issued by the Ministry of Health.
      Accreditation is not mandatory and is provided by an independent, non-commercial
      national accreditation body. The profession has interdisciplinary character and a
      level of required competence and skills comparable to other European countries.

PMID- 22141202
TI  - Graduate and postgraduate state university education of laboratory specialists in
      Hungary: medical doctors, pharmacists and laboratory analysts.
AB  - The authors focus on the description of graduate and postgraduate training of
      specialists working in clinical laboratories in Hungary. All training schemes are
      regulated by government decrees and, after obtaining an MSc degree, medical
      doctors and pharmacists may enter a specialty program for Medical Laboratory
      Diagnostics. For biologists, chemists and medical research laboratory analysts
      with an MSc degree a clinical biochemistry specialty training program is open.
      Regulated by law, the trainings are uniform in Hungary and are assigned to
      accredited medical universities. The candidates should complete a 26-month core
      program followed by 36 months' specific education. After a successful final
      examination including both practical skills and theoretical questions,
      specialists get a full license which will enable them to supervise laboratory
      work and validate test results. Laboratory specialists should join a continuous
      (lifelong) learning program and collect scores by attending special training
      courses. To receive a scientific degree, specialists may join PhD programs at any
      of the accredited universities.

PMID- 22141203
TI  - The organization of an educational program for specialists in clinical chemistry
      by the Greek Society of Clinical Chemistry-Clinical Biochemistry.
AB  - In Greece, there is no officially organized training in clinical chemistry for
      scientists. The Greek Society of Clinical Chemistry-Clinical Biochemistry decided
      to organize an intensive educational program of 18 seminars on clinical chemistry
      content as it is described in the EC4 Syllabus. The duration of each seminar was
      about 6 hours and consisted of 6 to 9 lectures. At the end of each seminar there
      was a voluntary written examination, comprised of 24 multiple choice questions.
      Successful completion of the Educational program was leading to a Certificate of
      Competence. Two cycles of the 18 seminars were performed: 1st cycle from October
      2003 to December 2005 and 2nd cycle from March 2005 to October 2007. One hundred
      eighty nine colleagues was the mean attendance per seminar for the seminars of
      the 1st cycle and 38 colleagues for the seminars of the 2nd cycle. The mean
      participation to the examination for each seminar was almost 80% for the 1st
      cycle and 68% for the 2nd cycle. More than 80% of the participants performed Good
      or Very good in the examination in both cycles. It is estimated that more than
      40% of the scientists who practice Clinical Chemistry in Greece, participated to
      this educational activity. This program is now provided as an e-learning
      application, and it is open for all scientists who want to follow the discipline
      of clinical chemistry.

PMID- 22141204
TI  - The state and the problems of the education in the sphere of clinical laboratory
      diagnostics in Ukraine.
AB  - The question of the medical laboratories staff training is currently in the focus
      of attention in Ukraine. Laboratory technicians with a college degree are
      prepared in the medical colleges for two or four years depending on school
      educational level. During their practice they are assessed every five years on
      completing the additional improving course. The position and their job
      responsibilities are defined by the Ministry of Health Protection. Bachelors of
      clinical laboratory diagnostics (CLD) are trained in medical universities
      obtaining the appropriate license. The position and their job responsibilities
      are similar to laboratory technicians' ones. The CLD specialists are prepared by
      the CLD departments in the medical academies of postgraduate education or medical
      universities' faculties of postgraduate studies. Those graduates, who have
      already acquired a degree in Medicine or Biology are eligible for the training
      program. Biologists pass courses of specialization for five month whereas doctors
      pass the specialization for ten month including four month practice. If the
      doctors wish, they can do the masters degree program within doing the
      specialization. However, because their position and job responsibilities are not
      determined by the Ministry of Health Protection of Ukraine, masters are allowed
      to practice their profession at the level of specialists. The specialists that
      practice clinical biochemistry, laboratory immunology, microbiology and medical
      genetics have to take the additional appropriate two-three month specialization
      courses. During their practice, specialists are assessed every five years. For
      assessment the commission takes into account the quantity of credits that a
      specialist has received within five years. Credits are earned for attending the
      scientific conferences, publishing scientific works, books or handbooks,
      professional training and pre-assessment module courses. The position and their
      responsibilities are defined by the Ministry of Health Protection of Ukraine.
      Currently there is no system in Ukraine for higher academic education for
      professionals in clinical laboratory diagnostics. We are aware of this fact and
      are committed to the improvement of the Ukrainian teaching clinical laboratory
      diagnostics system.

PMID- 22141205
TI  - Laboratory medicine education in Lithuania.
AB  - In Lithuania there are two types of specialists working in medical laboratories
      and having a university degree: laboratory medicine physicians and medical
      biologists. Both types of specialists are officially being recognized and
      regulated by the Ministry of Health of Lithuania. Laboratory medicine physicians
      become specialists in laboratory medicine after an accredited 4-year
      multidisciplinary residency study program in Laboratory Medicine. The residency
      program curriculum for laboratory medicine physicians is presented. On December
      9, 2009 the Equivalence of Standards for medical specialists was accepted and
      Lithuanian medical specialists in Clinical Chemistry and Laboratory Medicine can
      now apply for EC4 registration. Medical biologists become specialists in
      laboratory medicine after an accredited 2-year master degree multidisciplinary
      study program in Medical Biology, consisting of 80 credits. Various postgraduate
      advanced training courses for the continuous education of specialists in
      laboratory medicine were first introduced in 1966. Today it covers 1-2-week
      courses in different subspecialties of laboratory medicine. They are obligatory
      for laboratory medicine physicians for the renewal of their license. It is not
      compulsory for medical biologists to participate in these courses. The Centre of
      Laboratory Diagnostics represents a place for the synthesis and application of
      the basic sciences, the performance of research in various fields of laboratory
      medicine, as well as performance of thousands of procedures daily and provision
      of specific teaching programs.

PMID- 22141206
TI  - Comparison of methods: Passing and Bablok regression.
AB  - The comparison of methods experiment is important part in process of analytical
      methods and instruments validation. Passing and Bablok regression analysis is a
      statistical procedure that allows valuable estimation of analytical methods
      agreement and possible systematic bias between them. It is robust, non
      parametric, non sensitive to distribution of errors and data outliers.
      Assumptions for proper application of Passing and Bablok regression are
      continuously distributed data and linear relationship between data measured by
      two analytical methods. Results are presented with scatter diagram and regression
      line, and regression equation where intercept represents constant and slope
      proportional measurement error. Confidence intervals of 95% of intercept and
      slope explain if their value differ from value zero (intercept) and value one
      (slope) only by chance, allowing conclusion of method agreement and correction
      action if necessary. Residual plot revealed outliers and identify possible non
      linearity. Furthermore, cumulative sum linearity test is performed to investigate
      possible significant deviation from linearity between two sets of data. Non
      linear samples are not suitable for concluding on method agreement.

PMID- 22141207
TI  - Standardization of the hemoglobin A1c reporting: transferring global consensus to
      the local community--special report.

PMID- 22141208
TI  - Cardiac troponins and physical exercise. It's time to make a point.
AB  - The timely diagnosis of acute coronary syndrome (ACS), in particular myocardial
      infarction (MI), is still one of the most challenging issues in medicine. The
      introduction into routine laboratory practice of assays for measuring the
      cardiospecific troponins has dramatically revolutionized the diagnostic approach
      and the recent development of methods with improved analytical sensibility (i.e.,
      highly sensitivity [HS] assays), has further contributed to improve the negative
      predictive value of troponin testing but, contextually, has substantially lowered
      the clinical specificity of these markers. In particular, clinical studies have
      demonstrated the existence of an exercise-related increase of HS-troponins, with
      measurable values detectable in up to 94% of athletes undergoing endurance
      sports. This measurable amount oftroponin in blood would mirror an increased
      membrane permeability and early troponin release rather than reflecting a
      clinically threatening myocardial injury. As such, the measurable amount of
      cardiac troponins as assessed with the novel HS assays requires major clinical
      focus (i.e., serial measurement of cardiac biomarkers, detailed clinical history
      taking, integration with ECG and imaging findings) to prevent misdiagnosis of ACS
      and/or MI in otherwise healthy persons.

PMID- 22141209
TI  - Relationship between adiponectin and testosterone in patients with type 2
      diabetes.
AB  - INTRODUCTION: This study was designed to investigate the relationship between
      serum adiponectin and testosterone in patients with type 2 diabetes. MATERIALS
      AND METHODS: Serum level of adiponectin and testosterone were prospectively
      measured in 65 patients with type 2 diabetes and in 20 healthy subjects.
      Testosterone was determined by the radio-immunoassay whereas adiponectin levels
      were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The
      average serum testosterone did not differ between the diabetes and the control
      group, but the average adiponectin in the diabetes group was lower (14.6 (14.2
      15.0) vs. 24.3 (24.05-24.55) ng/mL, P = 0.001). In the diabetes group, the serum
      adiponectin level in patients with renal dysfunction (22.3 (21.5-23.1) ng/mL) was
      higher than in patients with no complications (12.1 (11.45-12.75) ng/mL) and than
      in patients with coronary artery disease (11.2 (10.25-12.15) ng/mL) (P = 0.009).
      Univariate correlation analysis showed an inverse weak correlation between
      adiponectin and testosterone concentrations in male diabetic patients (r = -0.27,
      P = 0.009). There was no significant correlation between adiponectin and
      testosterone in female patients (r = -0.05, P = 0.167). CONCLUSIONS: We conclude
      that patients with type 2 diabetes have lower serum adiponectin concentration
      than healthy individuals, and that there is a weak inverse correlation between
      adiponectin and testosterone serum concentrations in male diabetics.

PMID- 22141210
TI  - Effect of winter swimming on haematological parameters.
AB  - INTRODUCTION: Winter swimming represents an intensive short-term exposure to
      cold, and thus it is considered a strong physical stress. Cold-based treatments,
      i.e. immersions in cold water, are spreading in sport medicine for improving
      recovery following muscle traumas, although a universal acceptance of that method
      is not still achieved. MATERIALS AND METHODS: Fifteen healthy subjects (13 males
      and 2 females) were recruited among the participants to a 150 meters long
      swimming race in cold water (6 degrees C). Blood samples were collected the day
      before and immediately after the race and a panel of haematological parameters
      was evaluated. RESULTS: Swimming in cold water induced a significant variation in
      the blood cell fraction composition compared to the rest condition, as measured
      the day before the competition. Red blood cells, white blood cells and platelets
      count increased significantly (4.7%, P = 0.005; 40.6%, P < 0.001 and 25.0%, P <
      0.001, respectively). While the relative number of leukocytes did not change
      significantly, apart from a strong decrease of the eosinophils population (
      48.6%; P < 0.001), a strong increase in the total number of neutrophil
      granulocytes, lymphocytes and monocytes was recorded (42.6%, P = 0.002, 58.2%, P
      = 0.001 and 27.5%, P = 0.021, respectively). Following normalization on plasma
      volume change (-2.54%) the results were unchanged, demonstrating that the
      variations were not due to a mere haemoconcentration. CONCLUSIONS: When
      represented by brief exposure to cold water, winter swimming induces strong non
      pathological modifications of haematological homeostasis.

PMID- 22141211
TI  - Effects of hemolysis interferences on routine biochemistry parameters.
AB  - INTRODUCTION: Hemolysis is still the most common reason for rejecting samples,
      while reobtaining a new sample is an important problem. The aim of this study was
      to investigate the effects of hemolysis in different hemolysis levels for mostly
      used biochemical parameters to prevent unnecessary rejections. MATERIALS AND
      METHODS: Sixteen healthy volunteers were enrolled in the study. Four hemolysis
      levels were constituted according to hemoglobin concentrations and they were
      divided into five groups: Group I: 0-0.10 g/L, Group II:0.10-0.50 g/L, Group III:
      0.51-1.00 g/L, Group IV: 1.01-2.50 g/L, Group V: 2.51-4.50 g/L. Lysis was
      achieved by mechanical trauma. RESULTS: Hemolysis interference affected lactate
      dehydrogenase (LD) and aspartate aminotransferase (AST) almost at undetectable
      hemolysis by visual inspection (plasma hemoglobin < 0.5 g/L). Clinically
      meaningful variations of potassium and total bilirubin were observed in
      moderately hemolyzed samples (hemoglobin > 1 g/L). Alanine aminotransferase
      (ALT), cholesterol, gamma glutamyltransferase (GGT), and inorganic phosphate (P)
      concentrations were not interfered up to severely hemolyzed levels (hemoglobin:
      2.5-4.5 g/L). Albumin, alkaline phosphatase (ALP), amylase, chloride, HDL
      cholesterol, creatine kinase (CK), glucose, magnesium, total protein,
      triglycerides, unsaturated iron binding capacity (UIBC) and uric acid differences
      were statistically significant, but remained within the CLIA limits. CONCLUSION:
      To avoid preanalytical visual inspection for hemolysis detection, improper sample
      rejection, and/or rerun because of hemolysis, it is recommended in this study
      that, routine determination of plasma or serum free hemoglobin concentrations is
      important. For the analytes interfered with hemolysis, new samples have to be
      requested.

PMID- 22141212
TI  - Lipaemic samples: effective process for lipid reduction using high speed
      centrifugation compared with ultracentrifugation.
AB  - INTRODUCTION: Reducing laboratory errors and improving patient safety is
      receiving a lot of attention. Lipaemic samples are cause of analytical errors and
      present challenges for laboratories, particularly for those without
      ultracentrifuges. Lipaemia can originate from physiological (postprandial
      metabolism), para-physiological causes (e.g. IV administration of lipids) as well
      as metabolic disturbances (e.g. hypertriglyceridaemia). MATERIALS AND METHODS: We
      have evaluated a procedure with 10 native lipaemic sample pools (triglyceride
      concentration range 11.6-42.7 mmol/L) for the ability to reduce lipid
      concentration using a high speed micro-centrifuge (double centrifuged at 21.885 x
      g for 15 min) compared with an ultracentrifuge, and provide accurate results.
      Results of sodium, creatinine, urate, total protein, lactate dehydrogenase (LD),
      magnesium and, cholesterol and triglyceride analysis on a Beckman DxC800 analyser
      are presented. RESULTS: Data from our tertiary level hospital showed
      approximately 0.7% of the samples received for lipid studies have triglyceride
      levels > 10 mmol/L which can potentially cause analytical interference. The mean
      differences from the neat aliquot to the ultracentrifuged and high speed
      centrifuged sample pools were: cholesterol 4.9 mmol/L and 3.1 mmol/L; and
      triglycerides 17.4 mmol/L and 15.0 mmol/L respectively. The data confirms high
      speed centrifugation is almost as effective as ultracentrifugation in lipid
      reduction. CONCLUSION: The procedure utilized in this study using a high speed
      micro-centrifuge showed it is effective in reducing lipid levels and provides a
      suitable alternative to ultracentrifuged samples to provide accurate results.

PMID- 22141213
TI  - [Blood transfusion: a valuable resource to reserve for critical situations].

PMID- 22141214
TI  - [Parental presence in the operating room: effect on the quality of anesthetic
      induction and postoperative agitation in children].
AB  - BACKGROUND AND OBJECTIVE: Various nonpharmacologic strategies for reducing
      anxiety in children and improving cooperation during induction of anesthesia have
      been investigated. Parental presence during anesthetic induction has been the
      alternative studied most often, especially in English-speaking populations. Mixed
      results have been reported, however. The aim of this study was to evaluate the
      quality of anesthetic induction and the development of postoperative agitation in
      Spanish children undergoing ear, nose, or throat surgery with or without parental
      presence in the operating room. PATIENTS AND METHODS: Children in American
      Society of Anesthesiologists class 1 or 2 who were scheduled for ear, nose or
      throat surgery under inhalation anesthesia were randomized to 2 groups for
      presence or absence of a parent in the operating room. The induction experience
      was classified as easy, carried out with moderate resistance, or traumatic. The
      postoperative period was assessed as easy or traumatic. RESULTS: Forty children
      were randomized. Time to onset of anesthesia was similar in the 2 groups.
      Induction was easy for 65% of the children with parental presence and for 25% of
      the children without a parent present (P < .05). Induction was traumatic for 25%
      in the parental presence group and for 35% in the parental absence group (P <
      .05). The incidence of moderate resistance during induction was similar in the 2
      groups; the quality of the postoperative experience was also similar.
      CONCLUSIONS: Parental presence during induction of inhalation anesthesia improves
      the induction experience of nonpremeditated Spanish children, increasing the
      incidence of easy induction and decreasing the presence of traumatic induction.
      The quality of the postoperative experience is similar.

PMID- 22141215
TI  - [Reasons residents choose to specialize in anesthesiology and postoperative
      critical care in the autonomous community of Madrid].
AB  - OBJECTIVES: Our main objective was to determine the reasons why residents chose
      to specialize in anesthesiology and postoperative critical care in the autonomous
      community of Madrid. We also wished to know if prior contact with this specialty
      influenced their choice, if those who chose it as a second specialization
      differed from those who were doing a first residency, what expectations the
      residents had and if they had been met, and if they were satisfied with their
      training. MATERIAL AND METHODS: Survey of all residents in anesthesiology and
      postoperative critical care medicine in the community of Madrid between November
      2008 and February 2010. The questionnaire items covered demographic data, prior
      specialty training, undergraduate contact with the specialty, reasons for
      choosing this specialty (technical, social, or employment-related interests),
      satisfaction, and expectations met. RESULTS: We received 89 valid questionnaires,
      a sample that represented 35% of the residents. The reasons expressed most often
      were learning and performing techniques (97.8%); that the specialty was dynamic,
      with broad theoretical and practical content (98.9%), and an interest in
      providing critical care (93.3%). These 3 reasons were considered important or
      very important by most of the respondents; 55.8% considered that learning and
      carrying out techniques was the most important reason. All the respondents who
      had previously done specialty training said they were dissatisfied. Prior contact
      with the specialty was associated with having different reasons and interests,
      such as an interest in pain (F = .037) or emulating a role model (P = .014).
      CONCLUSIONS: The specialty's mix of theoretical and practical content and the
      chance to perform techniques and provide critical care are the features the
      residents find most attractive. Residents who already have another specialty are
      less satisfied and their expectations are not as well met.

PMID- 22141216
TI  - [Evaluation of a new computerized recording system for preoperative assessment
      data].
AB  - BACKGROUND AND OBJECTIVES: Little information is available on the use of
      computerized systems in preanesthetic assessment. Our aim was to evaluate staff
      acceptance of a computerized system for the structured recording of preoperative
      assessment data in our hospital. The time taken to complete the assessment was
      compared to the time usually taken to record the information on paper. MATERIAL
      AND METHODS: Observational, descriptive cross-sectional survey of user
      satisfaction 3 months after the system had been launched. We later carried out a
      prospective observational study of 796 preanesthetic assessment visits, comparing
      the mean time the users took to record information on paper to the time required
      to enter the data into the computer, analyzing differences between
      anesthesiologists and according to American Society of Anesthesiologists (ASA)
      classification and patient age. RESULTS: A total of 401 paper records and 395
      electronic files were included. The users believed that the computerized system
      improved quality and accessibility of recorded data and clinical decision-making.
      The time required to enter data into the computer was believed to be the main
      drawback; the users took a mean (SD) 15.21 (5.41) minutes to enter the electronic
      data and 13.37 (5.08) minutes to record the information on paper (P < .001).
      There were also significant differences in the time taken to record data
      according to ASA classification and between anesthesiologists (P < .001).
      CONCLUSIONS: In spite of drawbacks such as extra time taken to record electronic
      data, the users perceived benefits, such as improved quality and accessibility of
      records. For this reason, the computerized system was well accepted.

PMID- 22141217
TI  - [Efficacy of the fascia iliaca compartment block vs continuous epidural infusion
      for analgesia following total knee replacement surgery].
AB  - BACKGROUND AND OBJECTIVE: Total knee replacement causes moderate to severe
      postoperative pain. The aim of this trial was to compare postoperative analgesia
      from a fascia iliaca compartment block to continuous epidural analgesia following
      knee arthroplasty. PATIENTS AND METHODS: Clinical trial enrolling patients in
      American Society of Anesthesiologists (ASA) classes 1 to 3 randomized to 2
      groups. One group received spinal anesthesia plus a fascia iliaca compartment
      block with 0.1% bupivacaine at a rate of 10 mL/h. The second group received
      combined spinal-epidural anesthesia plus epidural analgesia with 0.1% bupivacaine
      in continuous infusion at a rate of 8 mL/h. Postoperative pain on a visual analog
      scale (VAS) at rest and on movement was recorded every 3 hours for the first 24
      hours. Use of intravenous morphine and the adverse events were also recorded.
      RESULTS: Forty patients (20 for each group) were enrolled. The distribution of
      age, weight, body mass index, sex, ASA class, duration of surgery, use of
      morphine, and the incidence of adverse effects were similar in the 2 groups.
      Postoperative VAS scores at rest and on movement were also similar. The incidence
      of arterial hypotension was higher in the epidural analgesia group. CONCLUSIONS:
      The fascia iliaca compartment block and continuous epidural infusion are
      similarly efficient in providing postoperative analgesia for patients after total
      knee replacement. The fascia iliaca compartment block is associated with a lower
      incidence of postoperative hemodynamic complications. Early, safe rehabilitation
      is facilitated by both analgesic techniques.

PMID- 22141218
TI  - [Nonanalgesic effects of thoracic epidural anesthesia].
AB  - Thoracic epidural anesthesia, which has been performed since the 1950s, has
      progressed from being one analgesic technique among others to its present status
      as the technique of choice for managing pain after major abdominal and thoracic
      surgery. In addition to providing effective analgesia, the epidural infusion of
      local anesthetic agents produces a sympathetic block that offers advantages over
      other types of pain control, particularly with respect to the cardiovascular,
      respiratory, and gastrointestinal systems. Thoracic epidural anesthesia provides
      dynamic pain relief, allowing the patient to resume activity early. It also
      permits early extubation and is associated with fewer postoperative pulmonary
      complications, shorter duration of paralytic ileus, and a better response to the
      stress of anesthesia and surgery. However, meta-analyses have not yet
      demonstrated that postoperative outcomes are improved. This review describes the
      nonanalgesic effects of thoracic epidural anesthesia.

PMID- 22141219
TI  - [Update on the current role of plasma cholinesterase].
AB  - The antagonism of steroidal nondepolarizing neuromuscular blockers (NDMBs) moved
      forward recently with the introduction of sugammadex, the only drug able to
      immediately reverse the effects of curarization produced by NDMBs. This advance
      has necessitated reflection on the future role of pseudocholinesterase. In spite
      of the side effects of succinylcholine and published opinions on its use, this
      NDMB continues to be used in clinical anesthesia. Pseudocholinesterase is mainly
      found in the liver, plasma, and nervous system. The enzyme is synthesized in the
      liver in greater amounts than required although certain conditions lead to
      deficiency, which is usually asymptomatic. The only clinical expression is the
      apnea which develops after administration of succinycholine because this NDMB
      cannot be metabolized. In some patients, slight reductions in the antagonism of
      succinylcholine lead to rising neuromuscular concentrations of the drug in
      accordance with the degree and duration of the blockade. We review the various
      forms of pseudocholinesterase deficiency, including a discussion of genetic
      variants, clinical manifestations, and management. In addition to discussing the
      diagnosis of this condition and the clinical implications, we highlight the
      importance of practice protocols and access to a referral laboratory if one is
      not available within the immediate hospital.

PMID- 22141220
TI  - [Sequential percutaneous surgical treatment in a woman with severe aortic
      stenosis and hypertrophic obstructive cardiomyopathy].
AB  - Quality of life is seriously compromised in both severe aortic stenosis and in
      hypertrophic obstructive cardiomyopathy. At advanced stages of disease, symptoms
      become incapacitating. Surgical correction is extremely effective, reducing
      symptoms and improving functional capacity. Percutaneous surgical techniques
      facilitate the treatment of patients in high-risk categories for whom
      conventional surgery is not an option. We report the case of a woman with severe
      symptomatic aortic stenosis and hypertrophic obstructive cardiomyopathy with
      associated mitral regurgitation. An aortic valve was implanted percutaneously.
      Later septal ablation was also performed percutaneously. The postoperative course
      was slow and the hospital stay was long. Percutaneous procedures provide a useful
      alternative way to treat severe symptomatic aortic stenosis and hypertrophic
      obstructive cardiomyopathy with mitral regurgitation, particularly when patients
      are at high risk for conventional surgery. These procedures are not without risk,
      however.

PMID- 22141221
TI  - [Serious complications after pulmonary radiofrequency ablation: report of 2
      cases].
AB  - Radiofrequency ablation can be used to treat primary or metastatic pulmonary
      tumors when surgery is not indicated or involves high risk. Although this
      technique is less invasive than surgical resection, it is not free of risk for
      complications and adverse events, especially when it is used in patients with
      serious respiratory disease in whom comorbidity is common. We report 2 cases of
      serious complications. One was an intractable air leak that led to death. The
      other was a large hemothorax that was brought under control in the radiology
      procedure room. We review the literature on this technique as well as
      recommendations that contribute to making it as safe as possible.

PMID- 22141222
TI  - [Noninvasive mechanical ventilation with a helmet in a patient with acute
      respiratory failure due to alveolar bleeding (Wegener granulomatosis)].

PMID- 22141223
TI  - [Airtraq tracheal intubation in a girl with Pierre Robin syndrome].

PMID- 22141224
TI  - [Accidental overdose of epidural morphine].

PMID- 22141225
TI  - [Remifentanil overdose in obstetric analgesia caused by a defective syringe in a
      patient-controlled analgesia system].

PMID- 22141226
TI  - [Local anesthetic leakage from the paravertebral space into the mediastinum].

PMID- 22141227
TI  - [Giant lumbar neurofibroma].

PMID- 22141228
TI  - Innovation requires clinical research.

PMID- 22141230
TI  - Complication rate of molar crowns: a practice-based clinical evaluation.
AB  - This practice-based study evaluates the initial clinical performance of
      conventionally luted metal-ceramic and zirconia molar crowns fabricated with a
      prolonged cooling period of the veneering porcelain. Forty-nine patients were
      treated (group A: high precious alloy + low fusing porcelain; group B: zirconia
      crowns). All zirconia crowns were veneered with a modified porcelain firing cycle
      including a 6-minute cooling period. Ninety-two restorations (74 vital
      abutments/18 nonvital abutments) were evaluated after a mean observation period
      of 18.2 +/- 4.6 months. No complete failures or loss of vitality were recorded in
      either group. Two events were recorded in group A (1 loss of retention/1 minor
      ceramic chipping < 2 mm2). The third event occurred in group B (minor ceramic
      chipping <2 mm2). All ceramic defects could be polished intraorally. Statistical
      analysis revealed non-significant differences in success rates (p = 0.91) of
      metal-ceramic and zirconia crowns fabricated with a modified porcelain firing.
      The modified firing of the zirconia porcelain seems to decrease the risk for
      early ceramic chipping in the molar area, leading to a technical complication
      rate comparable to that of metal-ceramic crowns.

PMID- 22141229
TI  - 10-year clinical outcomes of fixed dental prostheses with zirconia frameworks.
AB  - OBJECTIVES: The aim of this prospective clinical study was to assess the long
      term clinical survival rate and the technical and biological complication rates
      of zirconia-based posterior FDPs. MATERIALS AND METHODS: Forty-five patients in
      need of one or more posterior FDPs received 57 three- to five-unit zirconia-based
      FDPs. The frameworks were fabricated by means of a prototype computer-aided
      manufacturing (CAM) system (direct ceramic machining, DCM), first processing
      zirconia in the white stage. The frameworks were veneered with a prototype
      veneering ceramic.The FDPs were adhesively placed. At baseline, 6 months, and
      1,2, 3, 5, 8 and 10 years of function, the FDPs were examined for technical
      and/or biological complications. Furthermore, the periodontal health of the
      abutment teeth (test) and untreated control teeth was analyzed. Statistical
      analysis was performed applying descriptive statistics, Kaplan-Meier survival and
      multiple mixed effects regression tests. RESULTS: Twenty-one patients with 26
      FDPs were examined at a mean observation time of 10.7 +/- 1.3 years. A total of
      16 FDPs were lost to follow-up. Fifteen FDPs had to be replaced due to
      technical/biological complications; hence, the 10-year survival rate of the FDPs
      was 67%. Three framework fractures occurred, resulting in a 10-year survival rate
      for the zirconia frameworks of 91.5%. Chipping/fracture of the veneering ceramic
      was detected in 16 FDPs over 10 years (complication rate 32%). A significant
      correlation of the span of the FDPs and the incidence of chipping was observed: 4
      and 5-unit FDPs had a 4.9 times higher probability for chipping than 3-unit
      FDPs. Marginal discrepancy/degradation was found in 90.7% of the FDPs over 10
      years. At 11 of the FDPs (complication rate 27%), secondary caries occurred. No
      difference of the periodontal health was found around test and control teeth.
      CONCLUSION: The zirconia frameworks exhibited very good long-term stability.
      However, the zirconia-based FDPs frequently exhibited problems such as marginal
      deficiency or chipping of the veneering ceramic. Both problems may be associated
      with the prototype status of the system.

PMID- 22141231
TI  - Influence of preparation form, luting space setting and cement type on the
      marginal and internal fit of CAD/CAM crown copings.
AB  - PURPOSE: To evaluate the influence of two different tooth preparation forms, two
      luting space settings and two cement types on the marginal and internal
      adaptation of all-ceramic crown copings produced using Cerec3 CAD/CAM system.
      MATERIALS AND METHODS: Forty working stone dies were made from two metal master
      casts (1. Tooth 36: with anatomic occlusal reduction, 2. Tooth 36: with flat
      occlusal reduction). Forty crown copings were milled using Vita In-Ceram 2000 YZ:
      20 with an luting space settings of 0 = 100 microm and 20 with -50 = 50 microm.
      Copings were cemented using two cements (zinc phosphate cement, P21: Panavia21),
      then embedded and sectioned bucco-lingually and mesio-distally. Widths of
      marginal and internal gaps were measured using a light microscope at
      magnification of 40X. Data were submitted to one-way ANOVA, and statistical
      significance was set at p < 0.05. RESULTS: Copings with flat occlusal reduction
      and luting space settings of 100 pm had a better internal and marginal fit
      compared with copings with anatomic occlusal reduction and luting space settings
      of 50 microm, regardless of the cement used. P21 showed a significantly better
      fit compared with zinc phosphate cement. CONCLUSION: The presented Cerec3 CAD/CAM
      system can provide a marginal and internal adaptation which is comparable to that
      of conventional cast and conventional all-ceramic crowns.

PMID- 22141232
TI  - Analysis of jaw movements and muscle activity during mastication with JawReports
      Software.
AB  - We are currently developing new software for simultaneous visualisation and
      analysis of computerized recorded masticatory function and masticatory muscle
      activity. With the software, motion data recorded using the Jaw Motion Analyser
      and EMG data on masseter muscle activity can be uploaded in order to evaluate
      chewing activity immediately proximal to the occlusal surfaces. The software
      successfully differentiated between jaw opening and closing movements and
      filtered out muscle activity peaks, which were graphically depicted in the
      respective movement trajectories. This tracking strategy made it possible to
      visualize the movement sectors where chewing forces were effective and to
      estimate the strength of these forces. In the future, this software should
      improve our ability to analyze and assess the development of chewing forces.
      Therefore, it could provide a tool for optimal planning of implant-supported or
      CAD/CAM restorations.

PMID- 22141233
TI  - Computer-assisted pre- and postoperative evaluation of surgically assisted rapid
      maxillary expansion.
AB  - OBJECTIVE: Computer-assisted methods were used to evaluate different variants of
      surgically assisted rapid maxillary expansion (SARME) in terms of bone
      repositioning, new bone formation in the osteotomy gap, and bone quality before
      and after surgery. MATERIALS AND METHODS: Twenty-nine patients (18 male, 11
      female) with a mean age of 29 years (16 to 44 years) were included in the study.
      Surgically assisted rapid maxillary expansion with Le Fort I osteotomy was
      performed in all patients studied. High-resolution computed tomography (CT) was
      carried out directly before and 6 to 8 weeks after surgery. After registration of
      the preoperative CT data on the postoperative data, 3D models were constructed
      and superimposed. New bone formation in the osteotomy gap was visualized by means
      of a visualization procedure developed specifically for this purpose. Bone
      quality was analyzed by dividing the models into different anatomical segments. A
      qualitative comparison of the data was accomplished using a direct volume
      rendering procedure with a special transfer function. A quantitative comparison
      was carried out based on the pre- and postoperative histograms of each region.
      RESULTS: Maxillary widening was confirmed in all patients by computer-assisted
      analysis. Four patients exhibited significant maxillary asymmetry after surgery.
      New bone formation within the osteotomy gap was irregular along the osteotomy
      lines but often symmetrical on both sides. The more symmetrical the osteotomy,
      the more symmetrical the new bone formation proved to be. In all but two cases,
      the postoperative qualitative and quantitative analyses showed a significant
      decrease in Hounsfield units, particularly in the vestibular bone. CONCLUSION:
      The differences in new bone formation in the osteotomy gap suggest that the type
      of surgical technique and distractor used influence the outcome. Our results
      indicate that SAME results in a decrease in bone quality, particularly in the
      vestibular bone. Computer-assisted analysis clearly results in an information
      gain.

PMID- 22141234
TI  - CSA: the online portal for determining the clinical standing of ceramic
      restorations in practice.
AB  - For the individual dentist, the Ceramic Success Analysis (CSA) is atried and
      tested internet-based platform for monitoring the clinical success of all-ceramic
      restorations. After compiling an insertion protocol and recording the findings
      from regular clinical follow-up examinations, an analysis follows which
      culminates in the re-evaluation of the indication and the treatment approach. The
      evaluations of the 12-year results confirm a high success rate for all-ceramic
      restorations. Factors which influence the long-term success are: tooth vitality,
      an indicated crown, the use of a two-bottle dentin adhesive, and the placement of
      rubber-dam in the adhesive cementation technique.

PMID- 22141235
TI  - Digital veneering--manufacturing computer-generated veneers with the CAD-on
      technique.

PMID- 22141236
TI  - Input devices in the dental environment.

PMID- 22141237
TI  - Effect of tongue scraper and rinses on bad breath, a double-blind, randomized,
      parallel group clinical trial.

PMID- 22141238
TI  - I wonder if Richard Pryor suffered neck trauma.

PMID- 22141239
TI  - How to make a turnaround: despite a $40 million operating loss, one group
      practice managed to build a sustainable financial foundation.

PMID- 22141240
TI  - The importance of INSs: informatics nurse specialists bridge patients, IT and
      executives.

PMID- 22141241
TI  - Optimize your BI: five reasons healthcare business intelligence differs from
      other industries.

PMID- 22141242
TI  - A new era promises better outcomes: BPM systems are the best decision for
      decision-support software.

PMID- 22141243
TI  - Using big data for big impact. Leveraging data and analytics provides the
      foundation for rethinking how to impact patient behavior.

PMID- 22141244
TI  - New TIA-1179 standard supports IP convergence of CIS: Whether installed in a new
      hospital construction or as part of the modernization of an existing facility, a
      standards-based, IP-enabled communications network can deliver many benefits.

PMID- 22141245
TI  - Build a connected community of care: a standards-based HIE solution helps satisfy
      upcoming meaningful-use requirements.

PMID- 22141246
TI  - PACS re-envisioned.

PMID- 22141247
TI  - Launch EHRs with confidence.

PMID- 22141248
TI  - [Evolution of parasitism in mammal-associated mites of the group Psoroptidia
      (Acari:Astigmata)].
AB  - Host-parasite relationships of mammals and astigmatan mites (Acariformes:
      Astigmata) belonging to the parvorder Psoroptidia are analyzed. The absolute
      majority of mammal-associated psoroptidians belongs to the paraphyletic
      superfamily Sarcoptoidea. Mites of the family complex Psoroptidae (Lobalgidae,
      Psoroptidae, and Paracoroptinae) shifted from birds to placental mammals
      independently from each other. Mites of the family complex Sarcoptidae, including
      all other sarcoptoid families, derived from the common stalk of Psoroptidia
      independently from the Psoroptid complex. Mites of the sarcoptid complex shifted
      from nidicoly in mammalian nests to the permanent parasitism on these hosts. They
      are widely represented on both marsupial and placental mammals and are absent on
      Monotremata.

PMID- 22141249
TI  - [Detection of DNA erlichia and anaplasma in ticks Ixodes trianguliceps in Tyumen
      Province].
AB  - The data on the study of Ixodes trianguliceps Bir. collected from small mammals
      in the southern taiga forests of Tyumen Province with the PCR-hybridization with
      fluorescent detection method are given. DNA of Erlichua and Anaplasma was
      revealed in ticks of this species for the first time; mixed infection with both
      these pathogens was also demonstrated.

PMID- 22141250
TI  - [Seasonal dynamics of the parasite fauna and of the component community structure
      of parasites of the Minnow phoxinus phoxinus (L.) from the Pechora River].
AB  - The material represented by 120 specimens of minnow of the age 2(+)-3* was
      collected according to the standard technique from the Pechora River of the
      Pechora-Ilechsky reserve in the region of Central homestead during May-September
      2006. Three stages of the component parasite community included: the community in
      the process of formation (May-June), the formed community (June), the destroying
      community (July and August), the community in the process of formation (August
      and September).

PMID- 22141251
TI  - [Diversity of trematode larvae in gastropod molluscs in water bodies of Belarus].
AB  - The analysis of literary data and own investigations of gastropod molluscs on
      existence of cercariae of trematodes in Belarus was carried out. 13 856 specimens
      of 11 species and 2 species complexes of freshwater gastropod molluscs were
      examined on infection with cercariae of trematodes in 2010 by the authors of this
      article. Total infestation was 13.1% and infection of some molluscs species
      varied from 0.4% (Dnieper River, Gomel region) to 66.7% (Lukomskoe reservoir,
      Vitebsk region). The cercariae of 90 trematode species were found. The majority
      (51 species) at the adult stage parasitize birds. The cercariae of 14 trematode
      species have medical significance.

PMID- 22141252
TI  - [Some results of the study of the trematod fauna of the fresh-water molluscs
      Melanopsis praemorsa (L.) from water bodies in Azerbaijan. Communication 4. New
      species of cyathocotylid cercariae].
AB  - Pictures and descriptions of morphology and differential diagnosis of two new
      species of cyathocotylid cercariae--Cercaria agstaphensis 37 and Cercaria
      agstaphensis 38 are given. Special attention is paid to the structure of the
      glandular apparatus, excretory system, tegument armature, and other individual
      peculiarities of cercariae.

PMID- 22141253
TI  - [The influence of insulin on contamination of the common carp Cyprinus carpio by
      the monogenetic fluke Dactylogyrus vastator].
AB  - The influence of insulin on the contamination of the carp Cyprinus carpio with
      the monogenetic fluke Dactylogyrus vastator is studied. Fishes reacted to the
      introduction of the hormon by the decrease in the degree of intensity of
      infection and by the increase in the number of lifeless parasites on gills, by
      contrast to control fishes and fishes processed with stress hormones (adrenaline
      and cortisol). We assume that the decrease in the abundance index in live
      monogenetic fluke and the increase in the number of lifeless oness is caused by
      the deficiency of nutrients accessible for the growth and development caused by
      activation of hormone-induced anabolic processes and stimulation of mechanisms of
      immune protection.

PMID- 22141254
TI  - [Should the microsporidian spores be treated as dormant stages?].
AB  - Spores of bacteria, fungi, microsporidia and other protists are traditionally
      treated as dormant stages, intended to the long-term survival in the environment
      and to activation of parasitic forms during the infestation of a new host.
      However, in the process of examination of insect microsporidia at the molecular
      cellular levels and also at the level of organisms and populations, we came to a
      conclusion that spores are very active developmental stages with the entire
      potential directed to the rapid and successful infestation of new hosts during
      contact with the later. The work summarizes the original data demonstrating (1)
      the necessity of the rapid activation of microsporidian spores during host
      contact, (2) hopelessness of the long retaining of viability by spores of many
      microsporidia in the environment after leaving host organism; and (3) specific
      accumulation of metabolic ferments in "dormant" spores, but not in actively
      proliferating prespore developmental stages. On the basis of these data we
      conclude that microsporidian spores tend to shorten the period when they stay
      outside host organism to the maximal degree. The probability of host infestation
      within the limited time period increases due to diverse modes of transmission of
      pathogens, accumulation of maximally possible volume of infective spores, and the
      rapid mobilization of the extrusion apparatus.

PMID- 22141255
TI  - [Image of the month. Secretions secondary to a bronchoesophageal fistula].

PMID- 22141256
TI  - [Clinical case of the month. Sudden orbital cellulitis in the emergency unit].
AB  - We report a case of infectious orbital cellulitis complicating a frontal
      sinusitis in a seventy-three-year-old patient. The onset of this orbital
      complication was sudden. A clinical examination and an orbital CT-scan allowed an
      early diagnosis. Despite an appropriate surgical and medical treatment, the
      patient retains an altered visual function. We consider the clinical causes and
      consequences of orbital cellulitis as well as their surgical indications.

PMID- 22141257
TI  - [Clinical case of the month. Upper extremity deep venous thrombosis].
AB  - According to the studies, approximately 4 to 10% of all the cases of deep venous
      thrombosis are located in the subclavian, axillary or brachial veins. The more
      frequent use of central venous catheters and pacemaker leads is probably
      responsible for their increasing incidence these last decades. The deep venous
      effort thrombosis also called Paget-Schroetter Syndrome is part of the
      spontaneous upper extremity venous thromboses. They mostly affect young adults
      who practice special kinds of sports or whose professions require repetitive arm
      movements. Colour Duplex sonography provides a simple and accurate tool for the
      diagnosis of upper extremity deep venous thrombosis. Nowadays venography and
      venoscan are no longer used for diagnostic purposes. These techniques are limited
      to venous thromboses including to the brachiocephalic vein or the superior vena
      cava. This pathology can have major clinical consequences including pulmonary
      embolism and post-thrombotic syndrome. However, the prevalence of pulmonary
      embolism is controversial (20-35% according to studies) and fatal PE is very
      rare. Post-thrombotic syndrome mostly consists of venous stasis syndrome and
      painful exertion. Low molecular weight heparin followed by oral anticoagulation
      are recommended. Thrombolysis is often successful, but less frequently used
      because of its potential risks. Surgery may be required in case of venous
      compression (eg in case of thoracic outlet syndrome).

PMID- 22141258
TI  - [I beg your pardon? I can be treated by another modality than surgery for my
      vestibular schwannoma].
AB  - The history of the treatment of vestibular schwannoma (VS) clearly shows a shift
      from microsurgery towards radiotherapy as "standard therapy". The microsurgical
      approach obviously yields excellent tumour control, but is hampered by a high
      morbidity rate, especially at the level of cranial nerves. The literature reports
      a normal facial nerve function in only 60% of patients surgically treated for VS
      with a maximum diameter of 25 mm. Hearing preservation is only around 15% for
      tumours > 15 mm and around 50% for tumours less than 15 mm. Progress in
      techniques and computer sciences in the field of radiotherapy provides the
      opportunity to reach high levels of tumour control (92 - 98%), keeping cranial
      nerve morbidity on a very low level (< 2%). Hearing capacity and serviceable
      hearing can be maintained in about 70% of cases. Based on these results, one can
      assume that radiation therapy should be used upfront for those benign tumours.

PMID- 22141259
TI  - [The role of a systematic preoperative MRI before lumbar fusion in the prevention
      of transitional segment alterations].
AB  - Sacro-lumbar fusion must be carefully planned: to avoid alterations of the
      adjacent motion segments. This is a retrospective study to evaluate the fate of
      transitional segments at mid and long-term. The aim was to discuss the value of
      systematic preoperative MRI before spine fusion. The study group comprises 68
      patients who sustained a lumbar or sacro-lumbar fusion for degenerative
      discopathy or spondylolysis with spondylolisthesis between January 2000 and
      December 2005. The preoperative evaluation included standard radiographs and MRI.
      Postoperative follow-up averaged 51 months and ranged from 6 to 121 months. 72%
      of the patients had no clinical or radiological complications, 18% developed mild
      lesions such as a moderate disk space narrowing or osteophyte formation and only
      10% developed a significant adjacent motion segment alteration. The risk of
      degeneration increased with age, female sex, length of fusion and when the
      indication for fusion was a degenerative pathology. Compared with other studies,
      this work reports few true adjacent motion segment alterations because
      preoperative MRI allowed a better selection of the future adjacent segment.

PMID- 22141260
TI  - [Overview of acquired palmoplantar keratodermas].
AB  - Palmoplantar keratodermas affect a vast group of the population. Their origin is
      genetic or acquired. They represent manifestations of several distinct diseases.
      The precise semiologic examination is important for elucidating the differential
      diagnosis.

PMID- 22141261
TI  - [Mephedrone].
AB  - Mephedrone is a designer drug recently appeared on the belgian market of the
      drugs of misuse. The aim of this journal paper is to provide a review on the
      available data about mephedrone and to call the attention of the first line
      practitioners who will have to face this emerging problem.

PMID- 22141262
TI  - [Anal sphincter tears after vaginal delivery: risks factors and means of
      prevention].
AB  - To identify incidence and risks factors of obstetrical anal sphincter
      lacerations, we reviewed all cases of 3rd and 4th degree sphincter lacerations
      after vaginal deliveries (VD) occured in a tertiary maternity between 2005 and
      2010. 78 anal sphincter lacerations were identified (3.8/1000 deliveries). 66
      women (85%) were nulliparous. The mean age of women was of 29 +/- 5 years. The
      mean duration of the second stage of labour was of 3.4 +/- 1,7 hour. The birth
      weight of 12 newborns (15%) was greater than 4000 grams. Fourty-six women (2.5%)
      had sphincter lacerations after instrumental delivery and 32 after spontaneous
      vaginal delivery (0.2%). 51 patients out of 78 (65%) had a medio-lateral
      episiotomy, 82% occured after instrumental extraction and 43% after spontaneous
      delivery. A forceps of Tarnier was used in 18 cases, a Suzor forceps in 12 cases,
      spatula in 12 cases and vacuum in 4 cases. 76% of foetuses were in anterior
      presentation and 78% at the medium part of the pelvis. 2 patients experienced
      anal incontinence in early post-partum. Anal sphincter lacerations are relatively
      frequent after VD especially after instrumental delivery. Macrosomia, nulliparous
      women, prolonged second stage of labor were associated with anal sphincter tears.
      Medio-lateral episiotomy does not protect enough anal sphincters. Anal sphincter
      lacerations lead to anal incontinence in some cases.A long follow-up is useful
      for these patients.

PMID- 22141263
TI  - [How I explore ... the diagnosis of syphilis].
AB  - The versatility of the clinical presentations of syphilis is large. A laboratory
      diagnosis is required in any case where a clinical assumption is raised. Two main
      diagnostic methods are available according to the lesion aspects and the staging
      of the disease. They rely on the recognition of the spirochete or on the
      identification of the immune response using specific and non specific serology
      tests.

PMID- 22141264
TI  - [Mouse-induced pluripotent stem cells have the potential to differentiate into
      induced primordial germ cells].
AB  - OBJECTIVE: To investigate whether mouse-induced pluripotent stem (iPS) cell line
      IP14D-1 has the potential to differentiate into induced primordial germ cells
      (iPGCs), and to explore the changes in the expression of iPGCs-differentiation
      associated genes and their possible mechanisms. METHODS: Undifferentiated IP14D-1
      was cultured to proliferate and then differentiated to form 4-, 7- and 9-day-old
      induced embryoid bodies (iEBs) in vitro, respectively. RT-PCR and
      immunofluorescence were used to detect the expressions of Lin28, Blimpl, Stra8
      and Mvh, as well as the localization of the corresponding protein in iEBs.
      RESULTS: The expression of Blimpl was higher than that of Lin28 in the
      undifferentiated IP14D-1 and mouse embryonic stem cells (mESCs). Mvh and Stra8 as
      well as mESCs and EBs were also expressed in IP14D-1 and iEBs, but with no
      significant differences. The expression of Lin28 was gradually increased in the
      IP14D-1-derived iEBs from 4 to 7 days, but decreased at 9 days, and the
      expression of Blimp1 was gradually reduced with the prolonged growing time of
      iEBs. CONCLUSION: A stable system was established for the culture and
      differentiation of IP14D-1 and IP14D-1-derived iEBs. The expressions of Lin28,
      Blimp1, Mvh and Stra8 were not significantly different between the
      undifferentiated IP14D-1 and mESCs, nor were the expressions of Mvh and Stra8
      between iEBs and EBs. IP14D-1 and iEBs had the potential to differentiate into
      iPGCs, which increased in number in the 7-day-old iEBs, and the expression of
      iPGC-differentiation associated Lin28 became lower in the older iEBs.

PMID- 22141265
TI  - [Effectiveness of ICSI in patients with a high incidence of triploidy in a
      previous IVF cycle].
AB  - OBJECTIVE: To explore the effectiveness of ICSI in overcoming the high incidence
      of tripronucleates zygotes resulting from insemination in a previous IVF cycle.
      METHODS: We retrospectively analyzed the matched-pair cycles in 37 patients with
      a > 35 % incidence of tripronucleate zygotes in an IVF cycle, with ICSI used in
      the subsequent cycle, evaluated the incidences of diploid (2PN) and triploid
      (3PN) zygotesand the number of normal embryos obtained, and compared the rates of
      clinical pregnancy and embryo implantation between the IVF and ICSI groups.
      RESULTS: The mean age of the ICSI group was significantly older than that of the
      IVF group, while the ampules of gonadotropin and peak E2 showed no remarkable
      difference between the two. The numbers of follicles at hCG trigger, retrieved
      oocytes and mature oocytes were markedly lower in the former than in the latter.
      The percentage of 2PN was significantly higher while that of 3PN significantly
      lower after ICSI than after IVF (74.24% vs 34.42%; 11.57% vs 51.04%, P < 0.01),
      and more normal diploid embryos were obtained with ICSI (3.83 +/- 2.08 vs 2.52 +/
      1.71, P < 0.01). Four singletons were achieved in 31 IVF embryo transfer cycles,
      in comparison with 11 singletons and 3 twins in 36 ICSI embryo transfer cycles.
      The ICSI group showed significantly higher rates of clinical pregnancy and embryo
      implantation than the IVF group (38.89% vs 12.90%; 28.33% vs 7.41%, P<0.01).
      CONCLUSION: For women with a high incidence o triploidy in a previous IVF cycle,
      ICSI can effectively increase the number of normal diploid zygotes.

PMID- 22141266
TI  - [Sperm chromatin structure assay predicts the outcome of intrauterine
      insemination].
AB  - OBJECTIVE: Sperm chromatin structure assay (SCSA), as a clinically practical
      technique for the analysis of DNA damage, is rarely reported in China. This study
      focuses on the correlation of DNA damage with the pregnancy rate of intrauterine
      insemination (IUI). METHODS: We performed semen analysis for 482 couples
      undergoing IUI, calculated the DNA fragmentation index (DFI) by SCSA, and
      observed the relationship between DFI and the pregnancy rate of IUI. RESULTS:
      Clinical pregnancy was achieved in 5 (5.26%) of the 95 cases with DFI > 25%, and
      in 59 (15.25%) of the 387 cases with DFI < or = 25%. Those with sperm DFI >25%
      had significantly lower rates of biochemical pregnancy and clinical pregnancy
      than those with DFI < or = 25% (OR: 0.37, 95% CI: 0.14 - 0.96 and OR: 0.38, 95%
      CI: 0.16 - 0.97). No significant differences were found in the DFI of 54 cases
      between the first and the second cycle ([15.05 +/- 7.98]% vs [17.25 +/- 12.18]%,
      P > 0.05). Sperm DFI was significantly negatively correlated with sperm
      concentration, sperm motility and total progressively motile sperm count (P <
      0.01). CONCLUSION: The pregnancy rate of IUI is significantly lower in couples
      with DFI >25% than in those with DFI < or = 25%. Sperm DFI obtained from SCSA is
      partly correlated with sperm concentration and motility, and it is a robust
      predictor of the IUI outcome.

PMID- 22141267
TI  - [Flow cytometry for evaluation of sperm plasma membrane integrity in varicocele
      patients].
AB  - OBJECTIVE: To detect the sperm plasma membrane integrity (PMI) of varicocele (VC)
      patients using SYBR-14/PI fluorescent staining and flow cytometry, and
      investigate its clinical significance. METHODS: We collected semen samples from
      120 men, including 30 grade-1 varicocele patients (VC1), 30 grade-2 (VC2), 30
      grade-3 (VC3), and 30 normal fertile volunteer controls. Conventional semen
      analyses were performed by computer-assisted semen analysis (CASA). All the semen
      samples were washed with PBS and then subjected to SYBR-14/PI staining for the
      detection of sperm PMI by flow cytometry. The proportion of normal sperm with PMI
      was indicated as the percentage of sperm emitting green fluorescence (SYBR-14+/PI
      %), sperm PMI was determined and sperm fertilization capacity predicted.
      RESULTS: Significant differences were detected in SYBR-14+/PI- and SYBR-14-/PI+
      between the normal men and varicocele male patients (P < 0.01). The percentages
      of the sperm with PMI (SYBR-14+/PI- %) were remarkably lower in the VC1, VC2 and
      VC3 groups ([54.85 +/- 3.78]%, [45.37 +/- 4.12]% and [35.14 +/- 4.91]%) than in
      the normal controls ([70.79 +/- 6.71]%). SYBR-14+/PI-% was correlated positively
      with sperm motility (r=0.965, P < 0.01) and the percentage of grade a + b sperm
      (r = 0.874, P < 0.01), negatively with the percentage of grade d sperm (r = 
      0.965, P <0.01), but not significantly with pH, semen volume and liquefaction
      time (P > 0.05). CONCLUSION: SYBR-14/PI fluorescent staining and flow cytometry
      can quickly and exactly detect sperm PMI. Varicocele decreases sperm PMI, which
      might be an important cause of male infertility.

PMID- 22141268
TI  - [A comparative study of sperm morphology evaluation criteria by the fifth and
      fourth editions of WHO Laboratory Manual].
AB  - OBJECTIVE: To compare the criteria of sperm morphology evaluation in the fifth
      edition of WHO Laboratory Manual for the Examination and Processing of Human
      Semen and those in the fourth edition, and to know the changes in the criteria of
      sperm morphology evaluation in the new edition. METHODS: Nine technicians from
      Zhejiang Human Sperm Bank evaluated the morphology of 1 000 spermatozoa in 96
      sperm morphological pictures according to the criteria in the fourth and fifth
      editions of WHO Laboratory Manual, respectively. RESULTS: The percentage of
      morphologically normal sperm by the criteria of the fifth edition was (26.50 +/-
      5.06)%, significantly higher than (11.39 +/- 3.17)% by the fourth edition (P <
      0.05), while the rates of sperm head and tail defects based on the former were
      (64.26 +/- 7.66)% and (10.92 +/- 2.03)%, significantly lower than (76.11 +/-
      8.18)% and (39.89 +/- 3.85)% according to the latter (P < 0.05). There were no
      significant differences in the rates of sperm midpiece defects and excessive
      residual cytoplasm by the fifth and fourth editions ([16.46 +/- 3.08]% vs [15.22
      +/- 3.51 ]% and [4.24 +/- 1.66]% vs [3.87 +/- 1.68]%, P > 0.05). CONCLUSION: The
      criteria of sperm morphology evaluation in the fifth edition of WHO Laboratory
      Manual are less strict than those in the fourth, and the percentage of
      morphologically normal sperm is higher according to the fifth edition.

PMID- 22141269
TI  - [Gossypol decreases the expression of connexin 43 in Sertoli cells].
AB  - OBJECTIVE: To study the effect of gossypol on the expression of connexin 43
      (CX43) in Sertoli cells. METHODS: TM4 Sertoli cells were cultured and treated
      with gossypol at the concentrations of 1.25, 2.5, 5 and 10 micromol/L for 6, 12,
      24 and 48 hours. The cytotoxicity of gossypol was assessed by CCK-8 assay, and
      the expression of CX43 in the normal TM4 Sertoli cells and in those treated with
      different concentrations of gossypol for different times was detected by RT-PCR
      and immunofluorescence analysis. RESULTS: Semiquantitative RT-PCR and
      immunofluorescence analysis showed the expression of CX43 in the normal TM4
      cells. At 24 hours of exposure to gossypol, the expression began to decrease
      gradually with the prolonging of time and the increasing concentration of
      gossypol (P < 0.05). CONCLUSION: Gossypol reduces the expression of CX43 in TM4
      Sertoli cells, which might underlie the mechanism of its antifertility action.

PMID- 22141270
TI  - [Single nucleotide polymorphisms of CYP1A2 and their correlation with prostate
      cancer].
AB  - OBJECTIVE: To evaluate the correlation of the single nucleotide polymorphisms
      (SNPs) of the CYP1A2 gene with the stages and grades of prostate cancer (PCa).
      METHODS: We conducted gene sequencing of the rs2069514-3859 (A > G) and rs2069525
      1707 (C >T) alleles in the CYP1A2 gene in 253 patients with benign prostatic
      hyperplasia (BPH) and 206 patients with PCa treated by castration therapy, and
      statistically analyzed their correlations with the genotypes, stages and grades
      of prostate cancer. RESULTS: The incidences of the 2 CYP1A2 SNPs showed no
      significant difference between the BPH and the castrated PCa patients (P > 0.05),
      and their genotypes were not correlated with the stages of PCa (P > 0.05). The
      Gleason scores were mostly <7 in the PCa patients with genotypes containing C in
      the rs2069525-1707 (C > T) allele (P = 0.030, OR = 4.658, 95% CI: 1.222 -
      17.754). CONCLUSION: SNPs of the CYP1A2 gene may have some correlations with the
      pathologic stages of PCa, but their mechanisms and clinical significance need to
      be further confirmed.

PMID- 22141271
TI  - [Changes of nerve growth factor and M3 subtype muscarinic receptor in the seminal
      vesicle of diabetic rats].
AB  - OBJECTIVE: To investigate the effect of diabetic autonomic neuropathy on the
      seminal vesicle and search for the theoretical evidence for the prevention and
      treatment of diabetic infertility by observing changes in the contents of the
      nerve growth factor (NGF) and muscarinic M3 receptor in the seminal vesicle of
      diabetic rats. METHODS: Diabetic models were established in 10 of the 15 male
      adult SD rats by intraperitoneal injection of streptozotocin (STZ), and the other
      5 were included in a normal control group. Eight weeks after modeling, seminal
      vesicles were collected from the rats for HE and immunohistochemical staining.
      RESULTS: Compared with the normal controls, the diabetic models showed a
      decreased number of smooth muscle cells, thinner cytoplasm of glandular
      epithelial cells and disordered structure in the seminal vesicle. The intensity
      of NGF-positive staining was significantly enhanced, but that of M3 markedly
      reduced in the diabetic group. There were statistically significant differences
      in the mean integrated optical density (IA) of muscarinic M3 receptors and NGF
      between the control and diabetic groups (0.0187 +/- 0.0024 vs 0.0100 +/- 0.0015
      and 0.0209 +/- 0.0085 vs 0.0412 +/- 0.0117, P<0.01). CONCLUSION: The changes in
      the expressions of NGF and M3 receptors in the seminal vesicle of diabetic rats
      suggest that diabetes mellitus may induce autonomic neuropathy of the seminal
      vesicle.

PMID- 22141272
TI  - [Stage I testis teratoma in adults: treatment options and recurrence factors].
AB  - OBJECTIVE: To study the clinical outcomes of stage I testis teratoma, including
      pure teratoma, and to provide information on the treatment options for this
      disease. METHODS: We retrospectively analyzed 27 cases of orchiectomy for stage I
      testis teratoma, excluding epidermoid cyst, and investigated its recurrence
      associated with treatment methods and clinicopathological factors. RESULTS: Four
      of the 27 cases relapsed, all in the orchiectomy group and confined to the
      retroperitoneal region, 3 with and the other 1 without risk factors, but with no
      death. No recurrence was found in those treated by orchiectomy followed by
      chemotherapy with bleomycin, etoposide and platinum (BEP). The total rate of
      recurrence was 15.8%. No severe side effects were observed in the 9 patients
      undergoing adjuvant BEP chemotherapy. CONCLUSION: Risk factors may increase the
      recurrence rate of stage I testis teratoma, while postoperative adjuvant
      chemotherapy can reduce it, including that of pure teratoma, though surveillance
      policy remains the most popular option after orchiectomy.

PMID- 22141273
TI  - [Transurethral resection of the prostate for urinary retention after seed
      implantation for prostate cancer: report of 2 cases].
AB  - OBJECTIVE: To investigate the effect of transurethral resection of the prostate
      (TURP) in the treatment of urinary retention following seed implantation for
      prostate cancer. METHODS: We treated 2 cases of urinary retention following seed
      implantation for prostate cancer by TURP, and analyzed their clinical data.
      RESULTS: The operations were successful in both of the cases, with mean operation
      time of 60 min. Postoperative nocturnal urination of the patients averaged 2
      times per night as compared with 5 - 6 times per night preoperatively, and their
      scores on IPSS and quality of life were significantly improved after surgery.
      CONCLUSION: TURP affords satisfactory results in the treatment of urinary
      retention following seed implantation for prostate cancer patients.

PMID- 22141274
TI  - [Impacts of different transurethral prostatic resection procedures on male sexual
      function: meta-analysis of randomized controlled trials].
AB  - OBJECTIVE: To compare the impacts of transurethral resection of the prostate
      (TURP), transurethral electrovaporization of the prostate (TUEVP) and holmium
      laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic
      hyperplasia (BPH) on male sexual function. METHODS: We identified randomized
      controlled trials on the influence of TURP, TUEVP and HoLEP on the sexual
      function of BPH patients, and performed meta-analysis on the included data using
      Revman 5.0.25. RESULTS: Nine randomized controlled trials involving 1 050 BPH
      patients were included in the meta-analysis. The baseline of the study was
      comparable. TURP affected erectile function less than TUEVP (P = 0.04), but the
      two had no significant difference in their influence on ejaculatory function. Nor
      was any significant difference found between HoLEP and TURP in their influence on
      either erectile or ejaculatory function at 12 and 24 months after surgery.
      CONCLUSION: TUEVP induces a higher incidence of erectile dysfunction than TURP,
      but its influence on ejaculatory function is not significantly different from the
      latter. HoLEP and TURP have no significant difference in their influence on
      erectile function and ejaculatory function.

PMID- 22141275
TI  - [Hyperhomocysteinemia and erectile dysfunction: an update].
AB  - Hyperhomocysteinemia (HHcy) is considered to be one of the most important
      cardiovascular risk factors. Epidemiological studies conducted on erectile
      dysfunction (ED) have demonstrated its close correlation with cardiovascular
      disease, and therefore HHcy might be a novel risk factor of ED. However, the
      mechanism of ED resulting from HHcy is not precisely known, but may relate to
      increased damage of vascular endothelial cells, reactive oxygen species (ROS),
      and atherosclerosis. Although further studies are needed on this association
      between HHcy and ED, the measurement of plasma Hcy and folic acid levels and
      molecular analysis of the MTHFR genotype might be added to the ED diagnostic
      procedure, especially in young patients or in those with a family history of
      cardiovascular disease. Treatment of ED patients with HHcy should first aim to
      reduce the Hcy level through administration of folic acid, alone or in
      combination with vitamin B6 or B12, and then proceed to treatment with PDE5i.
      This paper offers an overview on the advances in the studies of the correlation
      between HHcy and ED.

PMID- 22141276
TI  - [Advances in researches on polymorphonuclear neutrophil elastase in semen].
AB  - Reproductive tract infection is one of the important factors of male
      reproduction. Polymorphonuclear neutrophil elastase (PMNE) in semen, as a marker
      of male reproductive tract inflammation, especially recessive infection,
      potentially affects male fertility. The concentration of PMNE in semen is
      correlated significantly not only with semen white blood cell count and seminal
      plasma ROS level, but also with the levels of other inflammation related
      cytokines, such as IL-6, IL-8, and TNF-alpha. Furthermore, PMNE has a negative
      impact on sperm quality by decreasing sperm motility, increasing the percentage
      of morphologically abnormal sperm and interfering with DNA integrity. PMNE
      inhibitors in semen can form a compound with PMNE, and the imbalanced proportions
      of the two may promote the development of chronic inflammation, and consequently
      lead to male infertility. At present, PMNE in semen is detected mainly by enzyme
      immunoassay, but this method still needs to be standardized, and the diagnostic
      standards to be unified.

PMID- 22141277
TI  - [Present status of clinical researches on the screening for prostate cancer
      biomarkers].
AB  - Researches on the biomarkers of tumors are very important for their early
      diagnosis and treatment. Although PSA has been used for over 20 years for
      screening prostate cancer and evaluating its treatment, the results are not
      entirely satisfactory. With the deepening of the researches on prostate cancer, a
      variety of prostate cancer biomarkers have been found. This article presents an
      overview on the recent advances in the screening for prostate cancer biomarkers.

PMID- 22141278
TI  - [Effects of Qiangjing Capsule on the oxidative and antioxidative system in the
      epididymis of varicocele rats].
AB  - OBJECTIVE: To observe the effects of Qiangjing Capsule (QC) on the oxidative amd
      antioxidative system in the epididymis of varicocele rats in comparison with
      those of Shaofuzhuyu Capsule (SC) and Wuziyanzong Capsule (WC), and to explore
      its possible mechanism of enhancing epididymal sperm maturation. METHODS: Ten of
      100 adolescent male SD rats were randomized to a sham-operation group, and
      varicocele models were successfully established in 72 of the other 90 by
      narrowing of the left renal vein. Then the model rats were equally assigned to 6
      groups: model control, high-dose QC (0.216 g/ml), medium-dose QC (0.108 g/ml),
      low-dose QC (0.054 g/ml), SC (0.146 g/ml), and WC (0.130 g/ml). After 4 weeks of
      treatment, we determined the activity of glutathione peroxidase (GPx) and the
      level of malondialdehyde (MDA) in the left epididymis of different groups of
      rats. RESULTS: Compared with the sham-operation group, the model group showed a
      significant decrease in GPx activity (P < 0.01) and a marked increase in the MDA
      level (P < 0.05). And the high-dose QC group exhibited a significantly hither GPx
      activity and lower MDA level than all the other groups (P < 0.01 and P < 0.05).
      CONCLUSION: Varicocele can reduce the activity of GPx and elevate the level of
      MDA in the epididymis of rats, while Qiangjing Capsule can increase the former
      and decrease the latter, and thereby may improve epididymal microenvironment,
      enhance epididymal sperm maturation and promote fertility.

PMID- 22141279
TI  - Epileptic syndromes: differential treatment in infants, children, and
      adolescents.
AB  - This paper proposes therapeutic guidelines for the management of some epileptic
      syndromes in infants, children, and adolescents, based on available medical
      literature and clinical practice in the French Community of Belgium. The
      guidelines address both epileptic encephalopathies (West syndrome, Lennox-Gastaut
      syndrome, and Dravet syndrome) and idiopathic epilepsies (typical absence
      seizures, epilepsy with centro-temporal spikes and juvenile myoclonic epilepsy).

PMID- 22141280
TI  - Cardiomyopathy in Friedreich's ataxia.
AB  - Friedreich's ataxia (FRDA), an autosomal recessive disorder, is characterized by
      spinocerebellar degeneration and cardiomyopathy. Here we explore some of the
      putative mechanisms underlying the cardiomyopathy in FRDA that have been
      elucidated using different experimental models. FRDA is characterized by a
      deficiency in frataxin, a protein vital in iron handling. Iron accumulation, lack
      of functional iron-sulphur clusters, and oxidative stress seem to be among the
      most important consequences of frataxin deficiency explaining the cardiac
      abnormalities in FRDA.

PMID- 22141281
TI  - The effects of FK506 on refractory inflammatory myopathies.
AB  - We performed an observational clinical study, the effects of tacrolimus (FK506)
      on the thymic output in patients with refractory inflammatory myopathies. Sixteen
      patients with polymyositis (PM) and 15 with dermatomyositis (DM) were treated
      orally with tacrolimus. Serum CK levels significantly decreased 2 to 4 months
      after tacrolimus therapy (p < 0.01), and MRC (Medical Research Council) scores
      were significantly improved 2 months after tacrolimus therapy (p < 0.01). T-cell
      receptor excision circle (TREC) content, a proxy for thymic export was not
      significantly different from that in age-matched controls, except for an increase
      in the TREC content within CD8+ single positive cells in patients with DM. TREC
      contents within double-positive cells and CD4+ single-positive cells were
      significantly decreased 4 M after tacrolimus therapy (p < 0.05) in PM/DM
      patients. Tacrolimus treatment significantly attenuated TREC content within
      cultured CD4+CD8- cells from PM/DMpatients (p < 0.05), but total cell counts were
      not significantly changed. These results indicate that tacrolimus therapy
      suppresses not only activated T-lymphocytes, but also some naive T-cell subsets
      in both PM and DM.

PMID- 22141282
TI  - Impact of carotid disease on posterior circulation in patients with vertebral
      artery occlusion--a functional transcranial Doppler study.

PMID- 22141283
TI  - The effects of clenbuterol on cerebral vasospasm in an experimental rat model of
      subarachnoid hemorrhage.
AB  - OBJECTIVE: To investigate the possible therapeutic effects of clenbuterol on
      cerebral vasospasm after subarachnoid hemorrhage (SAH) in rats. METHODS: Eighteen
      male albino Wistar rats, each weighing 200-250 g, were randomized into three
      groups; Group 1 (Control group) (n = 6) having no SAH and no treatment; Group 2
      (Sham group) (n = 6) having only SAH and Group 3 (Experimental group) (n = 6)
      having SAH treated with clenbuterol. Group 2 has been accepted as sham group to
      the experimental group. Experimental SAH was induced using a modified rat double
      hemorrhage model. Clenbuterol was administered twice daily in 12-hour intervals
      for three days at a dose of 0,1 mg/kg/day. The luminal diameter of the basilar
      artery was measured on each section with an optic micrometer by an experienced
      pathologist blinded to the groups. RESULTS: Mean basilar artery diameters were
      found to be different between the three groups (p < 0.001). Mean value of Group 2
      was significantly lower than that of Group 1 (p < 0.001). While mean value of
      Group 3 was significantly greater than that of Group 2 (p = 0.001), Groups1 and 3
      were found to be similar (p = 0242). CONCLUSION: Clenbuterol has favorable
      effects in the treatment of rat cerebral vasospasm (CVS). Further investigations
      are needed to evaluate both molecular effects and to find out effective treatment
      dose of clenbuterol on CVS.

PMID- 22141284
TI  - Protective effects of quercetin against status epilepticus induced hippocampal
      neuronal injury in rats: involvement of X-linked inhibitor of apoptosis protein.
AB  - Epilepsy is a common neurological disorder affecting people worldwide, and the
      recurrent spontaneous seizures are often seen post status epilepticus. Apoptosis
      and necrosis are two forms of neuronal death in post status epilepticus
      hippocampus, and the former has been widely studied and believed to be a major
      factor contributing to formation of abnormal excitatory circuit leading to
      refractory epileptic events. Thus, the need for development of new anti-epileptic
      agents remains urgent. Quercetin, a plant-derived bioflavonoid, is reported to
      have neuroprotective effects in neurological disease. We investigated protective
      effects of quercetin on status epilepticus induced hippocampal neuronal injuries
      in rats and focused on two major proteins, the X-linked inhibitor of apoptosis
      protein, a key member of the inhibitor of apoptosis protein family, and the
      caspase-3 protein, a common effector for the execution-phase of cell signaling
      apoptotic pathways. The number of apoptotic and surviving neurons were also
      counted in this study. We found expression alterations of X-linked inhibitor of
      apoptosis protein and caspase-3 protein in post status epilepticus hippocampus,
      along with an alteration in the number of apoptotic and surviving neurons.
      Furthermore, quercetin treatment in rats undergoing status epilepticus led to an
      interventional effect on expression of X-linked inhibitor of apoptosis protein
      and the caspase-3 protein, with a corresponding positive change on the number of
      hippocampal apoptotic and surviving neurons. Together, the study suggests
      neuroprotective effects of quercetin on hippocampal injury post status
      epilepticus and the effects may be associated with regulation of the X-linked
      inhibitor of apoptosis protein and the caspase-3 protein, which can be a decisive
      factor for apoptosis and survival of neurons in hippocampus.

PMID- 22141285
TI  - Importance of the initial grade of subarachnoid hemorrhage in the patients with
      the age of 80 years and older from a single center analysis.
AB  - In the developed countries, especially Japan, elderly population is rapidly
      increasing, but outcomes of elderly patients with the age of 80 years and older
      suffering from subarachnoid hemorrhage (SAH) remain still unclear. We
      retrospectively reviewed the medical records of nontraumatic SAH patients aged 80
      years and older, who were hospitalized in a single center between 1998 and 2009.
      There were 28 patients (80-90 years old and 75% female), representing 5.9% of all
      non-traumatic SAHs (n = 474). Of those, 16 patients received an intervention (ten
      clipping and six endovascular coiling) and the remaining 12 patients were managed
      conservatively. The median survival time of intervention group was 110 days and
      that of conservative group 49 days (p = 0.12, log rank analysis). Cox's
      proportional hazards model yielded two variables, the Japan Coma Scale (JCS)
      grade on admission ( hazard ratio: 2.93 [p = 0.009]) and conservative treatment
      (hazard ratio: 2.14 [p = 0.054]). In the outcome of the modified Rankin Scale
      between these two groups, logistic regression analysis had significant variable;
      the JCS grade on admission (odds ratio: 280, [p = 0.020]). In the elderly
      patients with good initial clinical condition, an acute intervention may have
      good outcome.

PMID- 22141286
TI  - Hidden in plain view: emergence of progressive multifocal leukoencephalopathy
      after treatment of CNS toxoplasmosis.
AB  - Multiple CNS infections can coexist in advanced AIDS, but are most commonly
      reported in autopsy case studies. We describe the case of an HIV+ individual, who
      was first diagnosed with CNS toxoplasmosis, confirmed by brain biopsy. After
      initiation of combined anti-retroviral therapy (cART) and successful treatment of
      CNS toxoplasmosis, he developed worsening neurological symptoms and was
      subsequently diagnosed with progressive multifocal leukoencephalopathy.
      Retrospective analysis of the MRI scans indicated that PML was already present
      early on but was interpreted as edema associated with CNS toxoplasmosis.
      Clinicians should be aware that multiple pathologies may coexist in the brain of
      immunosuppressed individuals and that PML may develop and worsen despite the use
      of cART.

PMID- 22141287
TI  - Acute chorea caused by valproate in an elderly.
AB  - We present the case of an elderly woman chronically treated with valproate as
      migraine prophylaxis. She developed acute chorea secondary to valproate dose
      increase. Choreiform movements ceased following valproate discontinuation. Chorea
      is a rare and dose dependent side effect of valproate.

PMID- 22141288
TI  - Primary headaches associated with sexual activity respond to topiramate therapy:
      a case report.
AB  - Primary headaches are rarely associated with orgasms. Indomethacin at doses of 25
      50 mg/day taken 30-60 minutes prior to sexual activity may prevent headaches.
      Propranolol and metoprolole have been used for headaches that consistently emerge
      during frequent sexual activity of any type. It is also known that topiramate is
      useful for treating migraines, but it is rarely used for other primary headaches.
      The role of topiramate in the treatment of headaches associated with sexual
      activity is unclear. Indomethacin and propranolol could not be used in our
      patient who, besides sexual activity-associated headaches, suffered from
      gastritis and diabetes mellitus. Thus, topiramate (50 mg/day) was used
      prophylactically, and sexual activity-associated headaches did not recur during 6
      months of topiramate therapy. This is the first report of positive response to
      topiramate as prophylactic treatment against sexual activity-associated headaches
      when propranolol and indomethacin are contraindicated.

PMID- 22141289
TI  - Left-sided hemihypomimia in Parkinson's disease.
AB  - Parkinson's disease is known to present and mostly persist as an asymmetrical
      movement disorder in most cases. The asymmetry is mainly described in motor
      features such as bradykinesia, rigidity and tremor in upper and lower limbs.
      Unilateral hypomimia however, has only been reported in 14 patients, all of whom
      showed right-sided hemihypomimia. In this case report we describe the symptoms of
      a 51-year-old man with predominant left-sided Parkinson's disease in whom we
      discovered a left-sided hemihypomimia. We also briefly review the literature
      concerning hemihypomimia in Parkinson's disease. We conclude that a larger case
      series needs to be studied to further elucidate the pathophysiology and clinical
      implications of this observation.

PMID- 22141290
TI  - Primary malignant meningeal melanomatosis: a clinical, radiological and
      pathologic case study.
AB  - A 40 year-old woman with subacute headache and visual impairment was admitted.
      Neurological examination revealed meningismus, diminished visual acuity,
      bilateral sixth cranial nerve palsy, and papillary edema. Dermatologic
      examination was normal. The brain CT scan showed hydrocephalus and hyperdense
      edging around fissures and sulci. The CSF study showed an increased protein
      level, with persistently negative microbiologic and cytological studies. Prior to
      Gd-DPTA injection, the brain T1-WI MRI revealed leptomeningeal hyperintensity. A
      dark subpial substance became evident at cerebral biopsy. The histopatological
      diagnosis was diffuse leptomeningeal melanomatosis. This case report highlights
      the diagnostic value of the brain MRI findings in primary leptomeningeal
      melanomatosis, a rare pathologic condition diagnosed in most published cases only
      after necropsy. Meningeal T1-WI hyperintensity prior to contrast injection is not
      caused by sarcoidosis or meningeal carcinomatosis, lymphomatosis or gliomatosis.

PMID- 22141291
TI  - Sporadic CJD in a patient with relaplsing-remitting multiple sclerosis on an
      immunomodulatory treatment.
AB  - Creutzfeld-Jacob disease (CJD) is a degenerative, invariably fatal brain
      disorder. Multiple sclerosis (MS) is a chronic, potentially disabling, immune
      mediated inflammatory demyelinating disease of the central nervous system. Here,
      we report a 50-year-old woman who, two years after the diagnosis of relapsing
      remitting MS, developed altered consciousness, dystonic posture of the left hand
      and myoclonic jerks. Repeated brain MRI showed hyperintensities on T2 sequences
      in basal ganglia bilaterally and diffusion restriction in these areas, and, since
      typical EEG and CSF features were present, the diagnosis of CJD was made. To the
      best of our knowledge, this is the first report of a glatiramer acetate-treated
      MS patient who developed sporadic CJD. This combination is interesting in the
      light of recent data suggesting that CJD and MS may share similar mechanisms of
      "molecular mimicry" and autoimmunity. This case also emphasizes the importance of
      critically assessing every new symptom even in a patient with an established
      diagnosis of MS.

PMID- 22141292
TI  - Cerebral venous thrombosis presenting with subarachnoid hemorrhage after spinal
      anesthesia.
AB  - A 22-year-old male had a meniscopathy operation using spinal anesthesia. After
      the operation, the patient reported a throbbing headache. His brain computed
      tomography (CT) showed subarachnoid hemorrhage (SAH) and hyperdense dural venous
      sinuses suspicious for thrombosis. Filling defects were observed in the superior
      sagittal and right transverse sinuses on the contrast-enhanced magnetic resonance
      images. The patient was diagnosed with cerebral venous sinus thrombosis (CVST).
      On the tenth day of his admission, his clinical findings progressed and heparin
      therapy was initiated after resorption of hemorrhage was observed in a second non
      contrast CT scan. The patient developed decreased consciousness the day after
      heparin administration. A subsequent brain CT revealed intraparenchymal
      hemorrhage in the right anteroinferior frontal region. Heparin therapy was
      discontinued, and anti-edema therapy was started. The presentation of CVST with
      SAH is a rare condition. Furthermore, development of CVST after spinal anesthesia
      is very rare. In this case, CVST developed after spinal anesthesia, and its first
      clinical presentation was SAH. To our knowledge, this is the first case CVST
      presenting with SAH after spinal anesthesia.

PMID- 22141293
TI  - Wegener's granulomatosis of the paranasal sinuses with orbital and central
      nervous system involvement-diagnostic imaging.
AB  - Wegener's granulomatosis (WG) is a systemic vasculitis that can affect any
      organic system, but primarily involves the upper and lower respiratory tracts and
      the kidneys. WG relatively frequently affects the nervous system (in 30-50%),
      usually in the form of peripheral or cranial neuropathy. Involvement of the brain
      is reported in a very small percentage of patients (2%-8%). Three major
      mechanisms have been described as the cause of central nervous system (CNS)
      disease in WG: contiguous invasion of granuloma from extracranial sites, remote
      intracranial granuloma and CNS vasculitis. CNS involvement caused by contiguous
      invasion of granuloma from extracranial sites is the rarest. We report the case
      of a 37-year-old man with WG, manifested as a pulmonary and paranasal sinuses
      disease, with orbital and CNS involvement, caused by contiguous invasion from the
      paranasal sinuses. In this report, the rich spectrum of findings achieved by
      computed tomography and magnetic resonance are demonstrated. The importance of
      computed tomography in bony destruction PNS findings, and the importance of MR
      imaging in evaluation of the direct intracranial spread from nasal, paranasal and
      orbital disease are also emphasized.

PMID- 22141294
TI  - Hyperexcitability of the facial nerve in tuberculous meningitis.
AB  - INTRODUCTION: Facial myokymias (FM) are continuous, involuntary, undulating
      movements of the facial muscles associated with spontaneous electromyographic
      activity, such as fasciculations and myokymic discharges. They may occur in
      healthy individuals, or be secondary to multiple sclerosis, posterior fossa
      tumors, or an inflammatory process. PATIENT AND RESULTS: We describe the case of
      a 31-year-old man who presented with headache, vomiting, low fever, and
      disorientation. Cerebrospinal fluid findings included low glucose and high
      protein content and lymphocyte pleocytosis, with positive culture for
      Myobacterium tuberculosis. The patient was diagnosed with tuberculous meningitis.
      Magnetic resonance imaging showed high contrast enhancement in the basal meninges
      and a left frontal tuberculoma. Over the course of the disease, he experienced FM
      and persistent, involuntary contraction of the facial muscles. The electromyogram
      recorded myokymic discharges. DISCUSSION: Tuberculous meningitis is a rare cause
      of FM. The presence of myokymic discharges on electromyography verified the
      peripheral origin of facial nerve hyperexcitability in this case, in contrast to
      persistent contraction of the facial muscles, which has a central origin. The
      phenomena were transitory and only positive symptoms were observed, with no
      facial nerve injury. CONCLUSION: Tuberculous meningitis is a rare cause of facial
      nerve hyperexcitability, which can have a peripheral, nuclear, or supranuclear
      origin.

PMID- 22141295
TI  - Temozolomide induced liver injury.
AB  - A 62-year female received radiotherapy over six weeks with daily 75 mg/m2
      Temozolomide (TMZ) for Glioblastoma (GB). At the last week of radiotherapy, her
      liver enzymes and serum bilirubin started deteriorating. TMZ was discontinued.
      The histopathology demonstrated the features of acute cholestasis and focal
      parenchymal inflammation. A range of investigations failed to show any other
      contributory cause of hepatitis. She required in-hospital care for a prolonged
      period for a grade three hepatic failure. The liver functions very slowly
      recovered over 40 weeks, but her general condition continues to deteriorate. TMZ
      may cause a mild temporary rise in the liver enzymes and has been reported to
      reactivate hepatitis B. In few other cases concomitant medications were the
      possible causes of hepatitis. However, searching the Medline and other
      bibliographic database, we have not come across any case of TMZ-induced liver
      injury (TMZ-DILI). Histopathology and pattern of liver enzyme elevation suggest
      that unlike Dacarbazine, which causes veno-occlusive type liver damage, TMZ in
      this patient caused mainly cholestasis type liver injury. On Naranjo Adverse Drug
      Reaction (ADR) probability scale, this case falls in probable grade (Scale 7).

PMID- 22141296
TI  - Idiopathic hypertrophic pachymeningitis responsive to mycophenolate.
AB  - Idiopathic hypertrophic pachymeningitis (IHP) represents a rare inflammatory
      condition that affects the central nervous system, often difficult to treat. We
      report the case of a patient who presented with difficulty in swallowing, slurred
      speech and ataxia associated with headache, vomiting and weight loss. He was
      diagnosed with IHP. He deteriorated despite treatment with high dose steroids and
      other immunosuppressants, including pulsed cyclophosphamide. Mycophenolate
      mofetil was therefore administered resulting in improvement and stabilization.
      This is the first report in English literature of the use of mycophenolate
      mofetil in the treatment of IHP and could stimulate further research in its
      efficacy in managing this condition.

PMID- 22141297
TI  - Familial paraganglioma syndrome.

PMID- 22141298
TI  - Wernicke's encephalopathy following chronic diarrhoea.

PMID- 22141299
TI  - Phantoms in the brain: transient mass in the posterior fossa after traumatic
      cervical SCI and vertebral artery obstruction.

PMID- 22141300
TI  - Giant aneurysm with dolichoectasia involving the carotid artery system.

PMID- 22141301
TI  - Armored brain with chronic headache.

PMID- 22141302
TI  - [We should not trivialize breast cysts].

PMID- 22141303
TI  - [Breast Centers: whim or necessity?].
AB  - In order to prevent disparities in the management of breast cancer having a
      direct impact on the prognosis of patients, to promote early detection and
      optimal treatment while considering the quality of life of patients, Breast
      Centers are being set up in Switzerland on the basis of existing models in
      Europe. The centers provide also follow-up of patients and are submitted to
      certification criteria established by the Swiss Society of Senology and the Swiss
      Cancer League. These criteria include in particular the expertise of specialists
      based on a sufficient volume of activity and training, compliance with
      recommendations of clinical practice, integration of supportive care and
      timeliness of care. The certification process is voluntary. A database enables
      the regular assessment of the provided care and of the compliance with standards.
      The aim and the modalities of the creation of the Breast Centers are discussed.

PMID- 22141304
TI  - [Psychosocial risk factors and preterm delivery].
AB  - Delivery before term (at less than 37 weeks of gestation) represents 5 to 10% of
      the deliveries and is an important cause of perinatal mortality and morbidity.
      Few improvements in prevention have been made. Difficulties include the
      multiplicity of medical risk factors, the absence of reliable diagnostic tests
      and the limited effectiveness of medical treatment. Several studies have shown
      that psychosocial risk factors are associated with preterm labour. The
      identification and management of these risk factors and of unfavorable social
      environment may potentially reduce the risk of preterm delivery. We describe and
      discuss the studies evaluating psychosocial interventions aiming at reducing the
      risk of prematurity.

PMID- 22141306
TI  - [Pelvic floor functions: from the beginning of the second phase of labor to the
      postpartum consultation].
AB  - Vaginal delivery can cause lesions of the various pelvic structures responsible
      for the mechanisms of continence. These lesions may perhaps be prevented in the
      future by measuring pressure generated during childbirth. Tear of the anal
      sphincter during childbirth is a marker of a global impairment of the urinary,
      ano-rectal and sexual pelvic functions in the short and medium term. Persistence
      of a defect of the anal sphincter is frequent in spite of immediate suture. The
      correlation between these defects and ano-rectal incontinence are not established
      in our experience. The quality of the contraction of the sphincter complex and
      pubo-rectal sling seems to play a more important role in ano-rectal continence
      after a traumatic childbirth.

PMID- 22141305
TI  - [Maternal heart disease and pregnancy: a multidisciplinary approach].
AB  - In developed countries, cardiovascular diseases are becoming one of the first
      causes of maternal death. Myocardial infarction, dissection of the thoracic aorta
      and cardiomyopathies are the leading causes. However, preexisting maternal
      cardiac diseases, such as congenital heart diseases, are more commonly
      encountered and may be associated with significant maternal and perinatal
      morbidity. This article reviews hemodynamic changes occurring during pregnancy,
      proposes a risk stratification according to pre-existing cardiac diseases, and
      discusses the monitoring and overall management of these patients. Finally, two
      pregnancy-triggered cardiac diseases are discussed: coronary artery disease and
      peripartum cardiomyopathy.

PMID- 22141307
TI  - [Laparoscopic management of genital prolapse by lateral suspension using mesh: a
      series of 377 patients].
AB  - Genital prolapse is frequent and can be found in about 50% of parous women. Its
      etiology is complex and multifactorial. Predisposing factors include: genetics
      (connective tissue disorders, family history); general state (age, parity,
      weight, smoking, obstructive pulmonary disease); trauma (carrying heavy loads,
      intense physical exercise); or iatrogenic (post hysterectomy). Treatment can be
      conservative or surgical and depends mainly on the severity of symptoms.
      Developments in surgical techniques and synthetic material in the last 20 years
      enabled us to use minimally invasive procedures with improved post operative
      course and decreased recurrence rates.

PMID- 22141308
TI  - [Weight gain and progestin-only contraceptives: more concern than evidence].
AB  - Weight gain is a side effect often associated with progestin-only contraceptives.
      A recently published Cochrane review focuses on this issue that has been
      addressed in only few studies of good quality. Here we discuss the results of
      this review in the context of three clinical cases. With progestin-only
      contraceptives the weight gain is less than often thought, especially after six
      or twelve months of treatment. Some results are rather reassuring, especially
      those in obese women and during the post-partum period. This should help improve
      the compliance of women who fear gaining weight with this type of hormonal
      contraception.

PMID- 22141309
TI  - [Superficial vein thrombosis: what's new in the management?].
AB  - Lower limbs superficial venous thrombosis (SVT) is a relatively frequent disease.
      Its prevalence among patients consulting their treating physician is estimated to
      be 10.8% among women and 4.9% among men. Up to 25% of at risk patients with
      isolated SVT present with a concomitant DVT. Ultrasound imaging may play a role
      in the management of these patients allowing precise diagnosis, determination of
      thrombus extension and presence of associated DVT. From data recently appeared in
      the literature treatment of SVT with prophylactic doses of fondaparinux may be
      proposed to at risk patients with isolated SVT.

PMID- 22141310
TI  - [Identification of the primary care physician and the quality of ambulatory
      medicine].

PMID- 22141311
TI  - [Homo connectus].

PMID- 22141312
TI  - [My new liver, this organ leaves my side (1)].

PMID- 22141313
TI  - [Public health on the doorstep of new federal legislation].

PMID- 22141314
TI  - [AIDS: questions surrounding contraception].

PMID- 22141316
TI  - [The origin of Apple].

PMID- 22141315
TI  - [Rugby confronted by alcohol].

PMID- 22141317
TI  - Development and certification of a standard reference material for vitamin D
      metabolites in human serum.
AB  - The National Institute of Standards and Technology (NIST), in collaboration with
      the National Institutes of Health's Office of Dietary Supplements (NIH-ODS), has
      developed a Standard Reference Material (SRM) for the determination of 25
      hydroxyvitamin D [25(OH)D] in serum. SRM 972 Vitamin D in Human Serum consists of
      four serum pools with different levels of vitamin D metabolites and has certified
      and reference values for 25(OH)D(2), 25(OH)D(3), and 3-epi-25(OH)D(3). Value
      assignment of this SRM was accomplished using a combination of three isotope
      dilution mass spectrometry approaches, with measurements performed at NIST and at
      the Centers for Disease Control and Prevention (CDC). Chromatographic resolution
      of the 3-epimer of 25(OH)D(3) proved to be essential for accurate determination
      of the metabolites.

PMID- 22141318
TI  - Nanofibrous microfiltration membrane based on cellulose nanowhiskers.
AB  - A multilayered nanofibrous microfiltration (MF) membrane system with high flux,
      low pressure drop, and high retention capability against both bacteria and
      bacteriophages (a virus model) was developed by impregnating ultrafine cellulose
      nanowhiskers (diameter about 5 nm) into an electrospun polyacrylonitrile (PAN)
      nanofibrous scaffold (fiber diameter about 150 nm) supported by a poly(ethylene
      terephthalate) (PET) nonwoven substrate (fiber diameter about 20 MUm). The
      cellulose nanowhiskers were anchored on the PAN nanofiber surface, forming a
      cross-linked nanostructured mesh with very high surface-to-volume ratio and a
      negatively charged surface. The mean pore size and pore size distribution of this
      MF system could be adjusted by the loading of cellulose nanowhiskers, where the
      resulting membrane not only possessed good mechanical properties but also high
      surface charge density confirmed by the conductivity titration and zeta potential
      measurements. The results indicated that a test cellulose nanowhisker-based MF
      membrane exhibited 16 times higher adsorption capacity against a positively
      charged dye over a commercial nitrocellulose-based MF membrane. This experimental
      membrane also showed full retention capability against bacteria, for example, E.
      coli and B. diminuta (log reduction value (LRV) larger than 6) and decent
      retention against bacteriophage MS2 (LRV larger than 2).

PMID- 22141321
TI  - Structure and conformational properties of 1,3,3-trimethyl-1,3-azasilinane: gas
      electron diffraction, dynamic NMR, and theoretical study.
AB  - Structure and the conformational properties of 1,3,3-trimethyl-1,3-azasilinane
      have been studied. According to gas electron diffraction (GED), the molecule
      exists in a slightly distorted chair conformation with the N-Me group in
      equatorial position. High-level quantum chemical calculations excellently
      reproduce the experimental geometry. Employing variable temperature (1)H and
      (13)C NMR spectroscopy down to 103 K, the conformational equilibrium could be
      frozen and the barrier to ring inversion determined.

PMID- 22141319
TI  - Strategies to mitigate the bioactivation of 2-anilino-7-aryl-pyrrolo[2,1
      f][1,2,4]triazines: identification of orally bioavailable, efficacious ALK
      inhibitors.
AB  - Chemical strategies to mitigate cytochrome P450-mediated bioactivation of novel
      2,7-disubstituted pyrrolo[2,1-f][1,2,4]triazine ALK inhibitors are described
      along with synthesis and biological activity. Piperidine-derived analogues
      showing minimal microsomal reactive metabolite formation were discovered. Potent,
      selective, and metabolically stable ALK inhibitors from this class were
      identified, and an orally bioavailable compound (32) with antitumor efficacy in
      ALK-driven xenografts in mouse models was extensively characterized.

PMID- 22141323
TI  - Enantioselective carbenoid insertion into phenolic O-H bonds with a chiral
      copper(I) imidazoindolephosphine complex.
AB  - The enantioselective O-H carbenoid insertion reaction with a new chiral copper(I)
      imidazoindolephosphine complex has been developed. The chiral copper(I) complex
      catalyzed the insertion of carbenoids derived from alpha-diazopropionates into
      the O-H bonds of various phenol derivatives to give the corresponding alpha
      aryloxypropionates with up to 91% ee.

PMID- 22141324
TI  - Opportunities for an alternative integrating testing strategy for carcinogen
      hazard assessment?
AB  - The 2-year rodent carcinogenicity bioassay evolved more than 40 years ago, and
      although it is complex, long lasting, expensive, and animal consuming, it is
      still the only generally accepted test for assessing the carcinogenicity of
      chemicals. Over time, different alternative approaches have been developed with
      the final goal to replace the bioassay. Unfortunately, at present, none of these
      strategies alone provides sufficient assurance of accurate prediction. In this
      review paper, we discuss the major advantages and pitfalls of the existing
      alternative methodologies to the carcinogenicity bioassay. Finally, based on the
      available scientific data in the public domain, we propose what we would like to
      call a "feasible integrated testing strategy" which incorporates some promising
      alternatives, providing at the same time information on the mechanism of action
      and the toxic nature of the compounds tested. It is, however, clear that the
      adoption of whatever "new" testing scheme should be considered with caution and
      its effectiveness should be experimentally demonstrated in advance by addressing
      a reasonable number of chemical carcinogens and non-carcinogens from a variety of
      structural and functional classes.

PMID- 22141325
TI  - Menopausal symptoms and risk factors for cardiovascular disease in postmenopause.
AB  - OBJECTIVES: Conflicting evidence indicates an increased risk for cardiovascular
      disease in postmenopausal women suffering from hot flushes. In this study, we
      tested whether, beyond hot flushes, menopausal symptoms are associated with
      biochemical and biophysical risk factors for cardiovascular disease. METHODS:
      Retrospective cross-sectional analysis on 951 women in surgical or physiological
      postmenopause, recruited at the menopause outpatient service of our university
      hospital between April 2002 and December 2009. The Greene Climacteric Scale and
      its subscales for anxiety, depression, somatic symptoms, vasomotor symptoms and
      sexuality were used to evaluate menopausal complaints. Blood pressure, fasting
      glucose and lipids levels were evaluated as risk factors for cardiovascular
      disease. Anthropometric parameters and those derived by remote and reproductive
      medical history were used as possible confounders. All data were anonymously
      retrieved from an electronic database. RESULTS: By multiple regression analysis,
      high density lipoprotein (HDL) cholesterol was inversely related to body mass
      index, the Greene Climacteric Scale score and years since menopause (R = 0.390; p
      = 0.0001). The total cholesterol/HDL cholesterol ratio was positively related to
      waist circumference and the Greene Climacteric Scale score (R = 0.356; p =
      0.0001). Triglycerides (R = 0.353; p = 0.0001) and triglyceride/HDL cholesterol
      (R = 0.425; p = 0.0001) were positively related to waist circumference, the
      Greene Climacteric Scale score and the Greene vasomotor subscore. Glucose was
      positively related to waist circumference, years since menopause and the Greene
      Climacteric Scale score (R = 0.390; p = 0.0001). Blood pressure was not related
      to menopausal symptoms. The 10-year risk for cardiovascular disease calculated by
      the Framingham formula was related independently and directly to body mass index
      and the Greene Climacteric Scale score (R = 0.183; p = 0.0001). CONCLUSIONS:
      Menopausal symptoms evaluated by a validated climacteric scale are associated
      with a worsening of biochemical risk factors for atherosclerosis and
      cardiovascular disease.

PMID- 22141326
TI  - Topical propranolol therapy for infantile hemangiomas.
AB  - The nonselective beta-adrenergic receptor antagonist propranolol is an effective
      therapy for infantile hemangiomas. Systemic propranolol therapy shows a rapid
      therapeutic effect with good drug tolerability. We report on the efficacy of
      local application of propranolol ointment in superficial hemangiomas of the skin.
      In our outpatient department, 45 children with 65 hemangiomas were treated with
      1% propranolol in a hydrophilic ointment topically applied twice a day. Before
      start of treatment and at each visit, clinical photographs were taken. If
      ultrasound did not confirm occult deeper components, children were included in
      the study. Treatment in the proliferative phase within the first 6 months of life
      (including seven preterm infants) induced regression in 59% and cessation of
      growth in 26% of the hemangiomas. No response or proliferation of subcutaneous
      components was observed in 15%. Clinically, no side effects caused by the beta
      receptor blocker were noticed. Treatment of two ulcerated hemangiomas of the
      perineal region twice using a flash lamp pulsed-dye laser and propranolol
      ointment in the surrounding lesion led to healing of the ulcers in 3 and 6 weeks,
      respectively. In six patients, topical therapy was started between the ages of 7
      and 33 months. Even in these hemangiomas, improvement was obvious after 2 or 3
      months. Propranolol administered topically in 1% ointment could have a beneficial
      effect on superficial hemangiomas of the skin. The treatment was well tolerated
      without side effects even in preterm infants and in children with numerous or
      large lesions.

PMID- 22141327
TI  - More academics in regular schools? The effect of regular versus special school
      placement on academic skills in Dutch primary school students with Down syndrome.
AB  - BACKGROUND: Studies from the UK have shown that children with Down syndrome
      acquire more academic skills in regular education. Does this likewise hold true
      for the Dutch situation, even after the effect of selective placement has been
      taken into account? METHOD: In 2006, an extensive questionnaire was sent to 160
      parents of (specially and regularly placed) children with Down syndrome (born
      1993-2000) in primary education in the Netherlands with a response rate of 76%.
      Questions were related to the child's school history, academic and non-academic
      skills, intelligence quotient, parental educational level, the extent to which
      parents worked on academics with their child at home, and the amount of academic
      instructional time at school. Academic skills were predicted with the other
      variables as independents. RESULTS: For the children in regular schools much more
      time proved to be spent on academics. Academic performance appeared to be
      predicted reasonably well on the basis of age, non-academic skills, parental
      educational level and the extent to which parents worked at home on academics.
      However, more variance could be predicted when the total amount of years that the
      child spent in regular education was added, especially regarding reading and to a
      lesser extent regarding writing and math. In addition, we could prove that this
      finding could not be accounted for by endogenity. CONCLUSION: Regularly placed
      children with Down syndrome learn more academics. However, this is not a straight
      consequence of inclusive placement and age alone, but is also determined by
      factors such as cognitive functioning, non-academic skills, parental educational
      level and the extent to which parents worked at home on academics. Nevertheless,
      it could be proven that the more advanced academic skills of the regularly placed
      children are not only due to selective placement. The positive effect of regular
      school on academics appeared to be most pronounced for reading skills.

PMID- 22141328
TI  - Enhanced extravasation, stability and in vivo cardiac gene silencing via in situ
      siRNA-albumin conjugation.
AB  - A potential barrier to progression of siRNA therapeutics to the clinic is the
      ability of these agents to cross the vascular endothelium to reach target cells.
      This study aimed to bypass the endothelial barrier by harnessing the
      extravasation capability of the serum protein albumin to allow siRNA to reach
      cardiomyocytes. A strategy for conjugating siRNA to albumin in vivo was developed
      that involved activating 3'-amine, 2'-O-methyl, phosphorothioate modified siRNA
      with succinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate (SMCC) to yield
      maleimide-functionalized siRNA ("activated siRNA"); this thiol-reactive species
      can then irreversibly link to the single surface-exposed cysteine residue of
      endogenous albumin following intravenous administration. An IGF-I-receptor (IGF
      IR) siRNA sequence which was effective in vitro was used to test the ability of
      the siRNA-albumin conjugate to bypass the endothelial barrier in Balb/C mice and
      produce silencing. In situ conjugation of maleimide-functionalized siRNA to
      albumin in mouse serum occurred within minutes of addition, and the resulting
      conjugate was found to be nuclease stable by SDS-PAGE analysis. In Sprague-Dawley
      rats, activated siRNA showed a significantly enhanced elimination half-life (75.9
      +/- 18.2 min) compared to unactivated siRNA (5.1 +/- 0.2 min). Intravenous
      injection of this activated siRNA (1 mg/kg daily for four days) significantly
      reduced left ventricle IGF-IR mRNA to 64.1 +/- 4.1% of that in vehicle-treated
      animals (mean +/- SEM), while the control siRNA (unconjugated) had no effect (n =
      4, P > 0.05). Imaging of microvessels from mice treated with fluorescein-labeled
      activated siRNA showed clear evidence of extravasation and cellular uptake in
      capillary endothelial cells, cardiomyocytes and vascular smooth muscle cells for
      mice treated with the activated siRNA but not mice treated with the unactivated
      siRNA. siRNA-albumin constructs are therefore capable of extravasation to the
      myocardium resulting in silencing in this otherwise silencing-resistant organ.

PMID- 22141329
TI  - Partial clamping of the renal artery during robot-assisted laparoscopic partial
      nephrectomy: technique and initial outcomes.
AB  - PURPOSE: We describe the feasibility of partial arterial clamping (PAC) during
      robot-assisted partial nephrectomy (RAPN). PATIENTS AND METHODS: We undertook a
      retrospective study of five patients who underwent PAC vs 17 who underwent
      complete hilar clamping (CHC). Estimated blood loss (EBL), transfusion rate,
      operative/console time, warm ischemia time (WIT), pathology, and postoperative
      glomerular filtration rate (GFR) were compared. RESULTS: PAC patients were older
      (P=0.002) and more likely to have had previous abdominal surgeries (P=0.032). PAC
      vs CHC was associated with higher median EBL (350 mL vs 75 mL, P=0.026), although
      there were no differences in blood transfusions (P=0.250). PAC was associated
      with shorter WIT (14 min vs 21 min, P=0.023). Positive margin rate and GFR change
      were similar. CONCLUSIONS: PAC offers a simple and reproducible technique that
      limits WIT during RAPN. PAC was not associated with more transfusions or positive
      margins. Further study is warranted to determine the utility of PAC with larger
      tumor size as well as the long-term benefits on renal function.

PMID- 22141330
TI  - Care closer to home for children and young people who are ill: developing and
      testing a model of service delivery and organization.
AB  - AIMS: To report findings of a national survey of care closer to home services for
      children and young people and a typology based on these findings. BACKGROUND:
      Providing care closer to home for children is a policy and practice aspiration
      internationally. While the main model of such services is children's community
      nursing, other models have also developed. Past research has proposed a
      relatively static typology of services, determined by where they are based,
      whether they are generic or specialist and whether they provide short- or longer
      term input. As services develop, however, this typology needs further
      elaboration. METHODS: A two-stage national survey of all primary care and
      hospital trusts in England, in mid-2008. RESULTS: In all, 67% of trusts responded
      to the screening questionnaire and 75% of relevant services to the main stage
      questionnaire. Thirteen distinct types of services were identified initially.
      Cluster analysis of delivery and organization characteristics then identified a
      three-model typology: hospital-based, condition-specific services (36%);
      children's community nurses and other community services (45%) and other (mainly
      therapy-based) services (19%). The models differed in staffing, costs, functions,
      type of care provided and geographical coverage. Only a third of nurses in teams
      were paediatric-trained. CONCLUSION: Care closer to home services are an
      established part of care for children and young people who are ill. They deal
      with complex and technical care and can prevent or reduce the length of acute
      hospital admission. Lack of readily available information about caseloads, case
      mix and costs may hamper their further development.

PMID- 22141331
TI  - Complications associated with tissue anchor migration after vaginal surgery using
      the tissue fixation system - a case series.
AB  - This case series describes eleven women with serious complications related to
      migration of tissue anchors after vaginal surgery for uterovaginal prolapse
      and/or urinary incontinence using the tissue fixation system.

PMID- 22141332
TI  - The utility of faces pain scale in a chronic musculoskeletal pain model.
AB  - OBJECTIVES: The main aim of this study was to investigate the clinical utility
      and sensitivity to change of faces pain scale (FPS) in patients with shoulder
      pain, chosen as a chronic pain model. The secondary aim was to determine the
      association of FPS with psychologic status and quality of life of these patients.
      METHODS: Thirty Turkish patients with chronic shoulder pain were included in the
      study. Pain intensity was evaluated by visual analog scale (VAS), which is a
      commonly used pain scale besides FPS. Depression and quality of life were
      screened by Beck Depression Inventory (BDI) and Short Form-36 (SF-36). All
      assessments were done before and after the physical therapy. RESULTS: There was a
      statistically significant decrease in pain severity after the treatment as
      indicated by FPS and VAS (P=0.000). The standardized response mean (SRM) value of
      FPS of 2.35 was accepted as a good responsiveness. The FPS showed a strong
      correlation with VAS (r=0.62 and 0.73) both before and after the treatment. Also,
      moderate to strong correlations were detected between the FPS and physical
      functioning (PF), physical role (PR), bodily pain (BP), emotional role (ER),
      general health (GH), mental health (MH) subscales of SF-36 (r=-0.58-0.80), and
      BDI scores (r=0.39) before the treatment. However, there were moderate and weak
      correlations with FPS and PR and social functioning (SF) subscales of SF-36 only
      after the treatment (r=-0.52 and r=-0.39). CONCLUSIONS: FPS is a satisfactory
      tool to assess pain in patients with chronic pain conditions and demonstrates
      sensitivity to detect changes after the treatment.

PMID- 22141333
TI  - Phosphorylation of yeast transcription factors correlates with the evolution of
      novel sequence and function.
AB  - Gene duplication is a significant source of novel genes and the dynamics of gene
      duplicate retention vs loss are poorly understood, particularly in terms of the
      functional and regulatory specialization of their gene products. We compiled a
      comprehensive data set of S. cerevisiae phosphosites to study the role of
      phosphorylation in yeast paralog divergence. We found that proteins coded by
      duplicated genes created in the Whole Genome Duplication (WGD) event and in a
      period prior to the WGD are significantly more phosphorylated than other
      duplicates or singletons. Though the amino acid sequence of each paralog of a
      given pair tends to diverge fairly similarly from their common ortholog in a
      related species, the phosphorylated amino acids tend to diverge in sequence from
      the ortholog at different rates. We observed that transcription factors (TFs) are
      disproportionately present among the set of duplicate genes and among the set of
      proteins that are phosphorylated. Interestingly, TFs that occur on higher levels
      of the transcription network hierarchy (i.e., tend to regulate other TFs) tend to
      be more phosphorylated than lower-level TFs. We found that TF paralog divergence
      in expression, binding, and sequence correlates with the abundance of
      phosphosites. Overall, these studies have important implications for
      understanding divergence of gene function and regulation in eukaryotes.

PMID- 22141335
TI  - Characterization of milled wood lignin (MWL) in Loblolly pine stem wood, residue,
      and bark.
AB  - Milled wood lignin samples from Loblolly pine stem wood, forest residue, and bark
      were isolated and characterized by quantitative (13)C and (31)P nuclear magnetic
      resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), and gel
      permeation chromatography (GPC) for molecular weight determination. Results from
      (13)C NMR show the stem wood and forest residue samples have similar functional
      group contents. However, the bark has fewer methoxyl groups, beta-O-4 structures,
      dibenzodioxocin, and side chains than the other two lignins. The bark lignin has
      the highest amounts of p-hydroxyphenyl (h) and C-5 condensed lignin, stem wood
      has the lowest, and the residue lies between. (31)P NMR analysis indicates that
      bark lignin contains more C-5 substituted phenolics and fewer aliphatic hydroxyl
      groups than the lignin isolated from stem wood or residue. The molecular weight
      distribution analysis indicates the bark lignin has higher weight-average
      molecular weight (M(w)) and polydispersity index than the lignin recovered from
      stem wood or residue.

PMID- 22141334
TI  - Comparison of neuromuscular and quadriceps strengthening exercise in the
      treatment of varus malaligned knees with medial knee osteoarthritis: a randomised
      controlled trial protocol.
AB  - BACKGROUND: Osteoarthritis of the knee involving predominantly the medial
      tibiofemoral compartment is common in older people, giving rise to pain and loss
      of function. Many people experience progressive worsening of the disease over
      time, particularly those with varus malalignment and increased medial knee joint
      load. Therefore, interventions that can reduce excessive medial knee loading may
      be beneficial in reducing the risk of structural progression. Traditional
      quadriceps strengthening can improve pain and function in people with knee
      osteoarthritis but does not appear to reduce medial knee load. A neuromuscular
      exercise program, emphasising optimal alignment of the trunk and lower limb
      joints relative to one another, as well as quality of movement performance, while
      dynamically and functionally strengthening the lower limb muscles, may be able to
      reduce medial knee load. Such a program may also be superior to traditional
      quadriceps strengthening with respect to improved pain and physical function
      because of the functional and dynamic nature. This randomised controlled trial
      will investigate the effect of a neuromuscular exercise program on medial knee
      joint loading, pain and function in individuals with medial knee joint
      osteoarthritis. We hypothesise that the neuromuscular program will reduce medial
      knee load as well as pain and functional limitations to a greater extent than a
      traditional quadriceps strengthening program. METHODS/DESIGN: 100 people with
      medial knee pain, radiographic medial compartment osteoarthritis and varus
      malalignment will be recruited and randomly allocated to one of two 12-week
      exercise programs: quadriceps strengthening or neuromuscular exercise. Each
      program will involve 14 supervised exercise sessions with a physiotherapist plus
      four unsupervised sessions per week at home. The primary outcomes are medial knee
      load during walking (the peak external knee adduction moment from 3D gait
      analysis), pain, and self-reported physical function measured at baseline and
      immediately following the program. Secondary outcomes include the external knee
      adduction moment angular impulse, electromyographic muscle activation patterns,
      knee and hip muscle strength, balance, functional ability, and quality-of-life.
      DISCUSSION: The findings will help determine whether neuromuscular exercise is
      superior to traditional quadriceps strengthening regarding effects on knee load,
      pain and physical function in people with medial knee osteoarthritis and varus
      malalignment. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      reference: ACTRN12610000660088.

PMID- 22141336
TI  - Expectancy for negative affect relief due to smoking may not be predictive under
      acute mood situations.
AB  - Smoking behavior may be more persistent among those who expect that smoking will
      relieve negative affect (NA). Assessing smoking expectancies temporally close to
      mood situations could enhance the predictive value of that assessment. Dependent
      smokers (n = 71; 43 male, 28 female) participated in five laboratory sessions,
      each involving mood induction. The NA relief scale of the Smoking Consequences
      Questionnaire-Adult (SCQ-A), a very common measure of smoking expectancies during
      hypothetical situations, was assessed during initial screening. The SCQ-A was
      compared with a modified acute version administered each session, in which items
      asked about immediate expectancy for NA relief by smoking "right now" (termed
      Immediate Negative Affect Relief, or INAR). Actual NA relief due to smoking was
      measured each session by change on the NA scale of the Diener & Emmons Mood Form.
      The five sessions (counterbalanced) involved three different negative mood tasks,
      the negative mood condition of overnight smoking abstinence, and neutral mood
      (control). Generalized estimating equations showed that temporal proximity to the
      mood situation slightly enhanced the ability of expectancy to predict actual
      change in NA due to smoking, as the interaction with condition was significant
      for the INAR but marginal for the SCQ-A. However, the acute INAR predicted NA
      relief due to smoking only after overnight smoking abstinence and not during the
      other specific mood induction conditions, contrary to expectations, while the SCQ
      A was not significant during any of the individual conditions. In sum, assessment
      of expectancy for NA relief may be of limited use in predicting actual NA relief
      from smoking during a current mood situation, aside from NA due to overnight
      abstinence.

PMID- 22141337
TI  - Ethanol inhibition of up-states in prefrontal cortical neurons expressing the
      genetically encoded calcium indicator GCaMP3.
AB  - BACKGROUND: The prefrontal cortex (PFC) is critically involved in working memory,
      cognition, and decision making; processes significantly affected by ethanol
      (EtOH). During quiet restfulness or sleep, PFC neurons show synaptically evoked
      oscillations in membrane potential between hyperpolarized down-states and
      depolarized up-states. Previous studies from this laboratory used whole-cell
      electrophysiology and demonstrated that in individual neurons, EtOH inhibited PFC
      up-states at concentrations associated with behavioral impairment. Although those
      studies monitored activity in 1 or 2 neurons at a time, it is likely that in
      vivo, larger networks of neurons participate in the complex functions of the PFC.
      In the present study, we used imaging and a genetically encoded calcium sensor to
      examine the effects of EtOH on the activity of multiple neurons simultaneously
      during up-states. METHODS: Slice cultures of mouse PFC were infected with an AAV
      virus encoding the calcium indicator GCaMP3 whose expression was driven by the
      neuron-specific synapsin promoter. After 2 to 3 weeks in culture, a fast CCD
      camera imaging system was used to capture changes in GCaMP3 fluorescence before,
      during, and after exposure to EtOH. RESULTS: PFC neurons displayed robust and
      reproducible changes in GCaMP3 fluorescence during evoked and spontaneous up
      states. Simultaneous whole-cell patch-clamp recording and GCaMP3 imaging verified
      that neurons transitioned into and out of up-states together. Acute application
      of EtOH reliably depressed up-state calcium signals with lower doses having a
      greater effect on up-state duration than amplitude. These effects of EtOH on up
      state parameters were reversed during washout. CONCLUSIONS: The results of the
      present study indicate that EtOH has profound effects on up-state activity in
      prefrontal neurons and suggest that this action may underlie some of the
      cognitive impairment associated with acute alcohol intoxication.

PMID- 22141338
TI  - Mn(II)-based porous metal-organic framework showing metamagnetic properties and
      high hydrogen adsorption at low pressure.
AB  - A Mn(II)-based homometallic porous metal-organic framework, Mn(5)(btac)(4)(MU(3)
      OH)(2)(EtOH)(2).DMF.3EtOH.3H(2)O (1, btac = benzotriazole-5-carboxylate), has
      been solvothermally synthesized and structurally characterized by elemental
      analysis, thermogravimetric analysis, and X-ray crystallographic study. 1 is a 3D
      neutral framework featuring 1D porous channels constructed by {Mn-OH-Mn}(n)
      chains and btac linkers. Magnetic studies show that 1 is a 3D metamagnet
      containing 1D {Mn-OH-Mn}(n) ferrimagnetic chains. High-pressure H(2) adsorption
      measurement at 77 K reveals that activated 1 can absorb 0.99 wt % H(2) at 0.5 atm
      and reaches a maximum of 1.03 wt % at 5.5 atm. The steep H(2) absorption at lower
      pressure (98.2% of the storage capacity at 0.5 atm) is higher than the
      corresponding values of some MOFs (MIL-100 (16.1%), MOF-177 (57.1%), and MOF-5
      (22.2%)). Furthermore, activated 1 can adsorb CO(2) at room temperature and 275
      K. The adsorption enthalpy is 22.0 kJ mol(-1), which reveals the high binding
      ability for CO(2). Detailed gas sorption implies that the exposed Mn(II)
      coordination sites in the activated 1 play an important role to improve its
      adsorption capacities.

PMID- 22141339
TI  - A survey to assess transfusion medicine education needs for clinicians.
AB  - OBJECTIVE: To evaluate the baseline knowledge of attending clinicians, residents
      and medical students in transfusion medicine (TM) at our institution in order to
      develop specialty-specific lectures. BACKGROUND: Physicians often receive minimal
      training in TM. Transfusion practices vary widely among individual physicians and
      across institutions. This variation leads to increased and unnecessary risk to
      patients and elevated costs for hospitals--problems that may be addressed through
      TM education. METHODS: An electronic self-administered survey was developed and
      administered to attending physicians, house staff and third and fourth year
      medical students at four hospitals. The survey consisted of 3 sections including
      background demographics, 14 knowledge assessment (KA) questions and opinions on
      educational needs. RESULTS: Two hundred and twenty-five surveys were received
      from physicians and medical students, of which 189 were completed and analysed.
      The overall mean score on the KA section was 31 . 4 +/- 18 . 3% (4 . 4 +/- 2 . 6
      of 14 questions) correct. Significantly stronger performance was noted in the
      following categories: participants in the specialties pathology or hematology
      (adult and pediatric), all fellows and participants who report greater than 5 h
      of formal TM education in the past 5 years. The majority of participants believed
      that additional training in TM was needed for themselves as well as other
      physicians at all training levels. CONCLUSIONS: Additional training in TM would
      be beneficial to and welcomed by physicians in all training levels in all
      specialties. Innovative specialty-specific educational programmes need to be
      developed and tested to ensure efficacy and durability.

PMID- 22141340
TI  - Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic
      fatty liver disease.
AB  - BACKGROUND AND AIM: A recent study in Indian subjects suggested common variants
      in apolipoprotein C3 (APOC3) (T-455C at rs2854116 and C-482T at rs2854117) to
      contribute to non-alcoholic fatty liver disease (NAFLD), plasma apoC3 and
      triglyceride concentrations. Our aim was to determine the contribution of genetic
      variation in APOC3 on liver fat content and plasma triglyceride and apoC3
      concentrations in a larger European cohort. METHODS: A total of 417 Finnish
      individuals were genotyped for rs2854116 and rs2854117 in APOC3 and the known
      rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3)
      influencing liver fat. Plasma apoC3 concentration was measured enzymatically, and
      liver fat by proton magnetic resonance spectroscopy. RESULTS: APOC3 wild-type
      homozygotes and variant allele (T-455C or C-482T or both) carriers did not differ
      with regard to liver fat, apoC3 concentrations, triglyceride-, high density
      lipoprotein-, fasting plasma glucose, insulin-, alanine aminotransferase- and
      aspartate aminotransferase-concentrations, nor was there a difference in
      prevalence of NAFLD. In contrast, carriers of the PNPLA3 GG genotype at rs738409
      had a 2.7-fold (median 11.3%) higher liver fat than those with the CC (median
      4.2%) genotype. The PNPLA3 rs738409 was also an independent predictor of liver
      fat, together with age, gender, and body mass index. CONCLUSION: Genetic variants
      in PNPLA3 but not APOC3 contribute to the variance in liver fat content due to
      NAFLD.

PMID- 22141341
TI  - Mechanism for folate-independent aldolase reaction catalyzed by serine
      hydroxymethyltransferase.
AB  - Serine hydroxymethyltransferase catalyzes the cleavage of beta-hydroxyamino acids
      into glycine and aldehydes in the absence of tetrahydrofolate. The enzyme accepts
      various beta-hydroxyamino acids as the substrate of this reaction. The reaction
      rate varies depending on the substituent and stereochemistry at the Cbeta atom:
      the erythro forms and the beta-phenyl substituent are preferred over the threo
      forms and the beta-methyl substituent, respectively. Although several mechanisms
      have been proposed, what determines the substrate preference remains unclear. We
      first performed quantum mechanical calculations to assess the validity of the
      reaction mechanisms. The results indicate that the retro-aldol mechanism starting
      with abstraction of the proton from the beta-hydroxyl group is plausible. This
      also suggests that Calpha-Cbeta bond cleavage is the rate-limiting step. We next
      measured the dependence of the rate constants on temperature with four
      representative substrates and calculated the activation energies and pre
      exponential factors from the Arrhenius plots. The activation energies of the
      erythro forms were lower than those of the threo forms. The beta-phenyl
      substituent lowered the activation energy in the threo form, whereas it did not
      alter the activation energy but increased the pre-exponential factor in the
      erythro form. We present a unified model to explain the origin of the substituent
      and stereochemical preferences by combining the theoretical and experimental
      results. A possible biological role of the tetrahydrofolate-independent activity
      in thermophiles is also discussed.

PMID- 22141343
TI  - The presence of pepsin in the lung and its relationship to pathologic gastro
      esophageal reflux.
AB  - BACKGROUND: Pepsin has been proposed as a biomarker of reflux-related lung
      disease. The goal of this study was to determine (i) if there is a higher reflux
      burden as measured by pH-MII in patients that are pepsin positive in the lung,
      and (ii) the sensitivity of pepsin in predicting pathologic reflux by pH, MII,
      and EGD. METHODS: We recruited children between the ages of 1-21 with chronic
      cough or asthma undergoing bronchoscopy, esophagogastroduodenoscopy (EGD), and
      multichannel intraluminal impedance (pH-MII) probe placement. The reflux profiles
      were compared between those patients who were pepsin positive and negative;
      proportions were compared using Chi-squared analyses and means were compared
      using t-testing. KEY RESULTS: Only the mean number of non-acid reflux events was
      associated with pepsin positivity (0.04). The sensitivity and specificity of
      pepsin in predicting pathologic reflux by pH-MII or EGD was 57% and 65%,
      respectively. The positive predictive value of pepsin in predicting pathologic
      reflux by pH, MII or EGD was 50% (11/22), and the negative predictive value was
      71% (20/28). There was a significantly higher mean LLMI in patients who were
      pepsin positive compared with pepsin negative patients (81 +/- 54 vs 47 +/- 26, P
      = 0.001). CONCLUSIONS & INFERENCES: Lung pepsin cannot predict pathologic reflux
      in the esophagus, but its correlation with lung inflammation suggests that pepsin
      may be an important biomarker for reflux-related lung disease.

PMID- 22141344
TI  - Gene expression and pathway analysis of ovarian cancer cells selected for
      resistance to cisplatin, paclitaxel, or doxorubicin.
AB  - BACKGROUND: Resistance to current chemotherapeutic agents is a major cause of
      therapy failure in ovarian cancer patients, but the exact mechanisms leading to
      the development of drug resistance remain unclear. METHODS: To better understand
      mechanisms of drug resistance, and possibly identify novel targets for therapy,
      we generated a series of drug resistant ovarian cancer cell lines through
      repeated exposure to three chemotherapeutic drugs (cisplatin, doxorubicin, or
      paclitaxel), and identified changes in gene expression patterns using Illumina
      whole-genome expression microarrays. Validation of selected genes was performed
      by RT-PCR and immunoblotting. Pathway enrichment analysis using the KEGG, GO, and
      Reactome databases was performed to identify pathways that may be important in
      each drug resistance phenotype. RESULTS: A total of 845 genes (p < 0.01) were
      found altered in at least one drug resistance phenotype when compared to the
      parental, drug sensitive cell line. Focusing on each resistance phenotype
      individually, we identified 460, 366, and 337 genes significantly altered in
      cells resistant to cisplatin, doxorubicin, and paclitaxel, respectively. Of the
      845 genes found altered, only 62 genes were simultaneously altered in all three
      resistance phenotypes. Using pathway analysis, we found many pathways enriched
      for each resistance phenotype, but some dominant pathways emerged. The dominant
      pathways included signaling from the cell surface and cell movement for cisplatin
      resistance, proteasome regulation and steroid biosynthesis for doxorubicin
      resistance, and control of translation and oxidative stress for paclitaxel
      resistance. CONCLUSIONS: Ovarian cancer cells develop drug resistance through
      different pathways depending on the drug used in the generation of
      chemoresistance. A better understanding of these mechanisms may lead to the
      development of novel strategies to circumvent the problem of drug resistance.

PMID- 22141346
TI  - The adjuvant treatment of partial seizures in epilepsy: focus on lacosamide.
      Foreword.

PMID- 22141345
TI  - Desmin expression in colorectal cancer stroma correlates with advanced stage
      disease and marks angiogenic microvessels.
AB  - INTRODUCTION: Biomarkers that improve stratification of colorectal cancer
      patients for adjuvant therapy versus resection alone, or that are predictive of
      response to therapeutic agents, have the potential to greatly improve patient
      selection for such therapies. The aim was to determine proteins differentially
      expressed within the malignant epithelial glands and closely associated stromal
      elements compared to matched normal mucosa, and to characterise the over
      expression of one such protein as a potential biomarker. METHODS: Protein from
      laser microdissected tumor and normal mucosa was analysed by two dimensional
      difference gel electrophoresis (2D DIGE) and mass spectrometry to determine
      differentially over expressed tumor proteins. Tumor over-expression of one such
      protein, desmin, was quantified using immunofluorescence staining in a larger
      cohort. Dual staining for desmin and vimentin, or desmin and von Willebrand
      factor, was performed to determine the cell type of interest. RESULTS: Desmin
      expression was significantly increased between stage I and III tumors, (P <
      0.0001), and stage II and III tumors, (P < 0.0001). Strong focal desmin
      expression was found in stroma directly adjacent to carcinomatous glands and
      microvessels. These cells showed co-localisation of desmin and vimentin in close
      association with cells expressing VWF, indicating they were pericytes.
      Significantly higher levels of desmin-positive pericytes were observed in late
      stage tumors, consistent with increased angiogenesis. CONCLUSION: Pericyte
      coverage of vasculature is a marker of vessel maturation, hence desmin expression
      may have use as a marker for microvessel maturation. Clinical trials will be
      needed to determine its use in identifying tumors that will be less responsive to
      anti-angiogenic therapy.

PMID- 22141347
TI  - Review of therapeutic options for adjuvant treatment of focal seizures in
      epilepsy: focus on lacosamide.
AB  - Epilepsy is one of the most common serious neurological conditions worldwide,
      with an age-adjusted incidence of approximately 50 per 100,000 persons per year
      in developed countries. Antiepileptic therapy can result in long-term remission
      in 60-70% of patients, but many patients will require combination treatment to
      achieve optimal seizure control, as monotherapy is ineffective at controlling
      seizures in 30-53% of patients. Despite the increase in available treatment
      options, patient outcomes have not improved significantly and there is still a
      need for more effective therapies. Drugs used in the treatment of focal-onset
      seizures are a diverse range of compounds, and in most cases their mechanism of
      action is unknown or poorly defined. This review discusses the efficacy and
      safety of the newer adjuvant antiepileptic therapies that may improve outcomes in
      patients unresponsive to monotherapy, including clobazam, vigabatrin,
      lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam, oxcarbazepine,
      pregabalin, zonisamide and eslicarbazepine, with focus on lacosamide. Lacosamide
      has been shown to exert its anticonvulsant effects predominantly by enhancement
      of the slow inactivation of voltage-gated sodium channels. Lacosamide is
      indicated for use as adjuvant treatment of focal-onset seizures in patients with
      epilepsy, and there is some evidence that it may also be of use in patients with
      status epilepticus and cancer patients with epilepsy. The efficacy of lacosamide
      has been assessed in three randomized, double-blind, placebo-controlled clinical
      trials, all of which have shown lacosamide to be effective at reducing seizure
      frequency and increasing 50% responder rates in patients with focal-onset
      seizures. Long-term lacosamide treatment is generally well tolerated and is not
      associated with significant drug interactions; the availability of an intravenous
      form of the drug also makes it particularly useful for a broad range of patients.

PMID- 22141348
TI  - Lacosamide for epileptic seizures in patients with co-morbidities and unusual
      presentations of epilepsy.
AB  - Numerous patients who are prescribed antiepileptic drugs (AEDs) for epileptic
      seizures are already receiving other agents for the treatment of co-morbid
      conditions, which frequently occur alongside epilepsy. This raises additional
      clinical considerations and makes the use of AEDs with good safety profiles and
      fewer drug-drug interactions attractive. Second and third-generation
      anticonvulsant drugs are associated with fewer pharmacological interactions and
      improved tolerability compared with first-generation drugs. Furthermore, second
      and third-generation anticonvulsant drugs are associated with linear
      pharmacokinetic profiles and differing mechanisms of action, making them ideal
      for pluripathological and polymedicated patients. In this report, we highlight
      the efficacy of one such agent, lacosamide, in five patients with co-morbidities
      and unusual presentations of epilepsy, including a patient with paraneoplastic
      encephalitis caused by microcytic lung carcinoma, one with a brain tumour and one
      with Alzheimer's disease, as well as a case of catamenial epilepsy and one of
      refractory convulsive status epilepticus. In all patients, lacosamide was
      associated with a substantial reduction in seizure frequency and effective
      control of seizure episodes. Treatment was generally well tolerated in all
      patients, indicating that lacosamide is an effective treatment option for a
      variety of patients with epileptic seizures.

PMID- 22141351
TI  - CYP2D6 and the severity of suicide attempts.
AB  - AIM: Among people who die by suicide, an increased frequency of CYP2D6 active
      gene multiplication has been described. Therefore, the present study analyzed the
      relationship between the severity of the suicidal intent and CYP2D6 number of
      active genes among survivors. MATERIALS & METHODS: A group of 342 individuals
      were evaluated with Beck Suicide Intent Scale within 24 h of the failed attempt.
      'Severe' suicide attempters were classified as those scoring above percentile 75
      in the objective circumstances section of the Suicide Intent Scale Scale. A group
      of 377 healthy controls were also genotyped. results: A higher number of 'severe'
      suicide attempters carrying >=2 active CYP2D6 genes as compared with the rest of
      the patients population (p < 0.01) or the healthy control group (p < 0.01) was
      found. CONCLUSION: Considering that 'severe' suicide attempters are more likely
      eventually to die by suicide, CYP2D6 genetic polymorphism might be of use as a
      biomarker of death by suicide, which is in agreement with previous findings.

PMID- 22141353
TI  - Direct analysis of phycobilisomal antenna proteins and metabolites in small
      cyanobacterial populations by laser ablation electrospray ionization mass
      spectrometry.
AB  - Due to their significance in energy and environmental and natural product
      research, as well as their large genetic diversity, rapid in situ analysis of
      cyanobacteria is of increasing interest. Metabolic profiles and the composition
      of energy harvesting antenna protein complexes are needed to understand how
      environmental factors affect the functioning of these microorganisms. Here, we
      show that laser ablation electrospray ionization (LAESI) mass spectrometry
      enables the direct analysis of phycobilisomal antenna proteins and report on
      numerous metabolites from intact cyanobacteria. Small populations (n < 616 +/-
      76) of vegetative Anabaena sp. PCC7120 cyanobacterial cells are analyzed by LAESI
      mass spectrometry. The spectra reveal the ratio of phycocyanin (C-PC) and
      allophycocyanin (APC) in the antenna complex, the subunit composition of the
      phycobiliproteins, and the tentative identity of over 30 metabolites and lipids.
      Metabolites are tentatively identified by accurate mass measurements, isotope
      distribution patterns, and literature searches. The rapid simultaneous analysis
      of abundant proteins and diverse metabolites enables the evaluation of the
      environmental response and metabolic adaptation of cyanobacteria and other
      microorganisms.

PMID- 22141352
TI  - Targeting of histone acetyltransferase p300 by cyclopentenone prostaglandin
      Delta(12)-PGJ(2) through covalent binding to Cys(1438).
AB  - Inhibitors of histone acetyltransferases (HATs) are perceived to treat diseases
      like cancer, neurodegeneration, and AIDS. On the basis of previous studies, we
      hypothesized that Cys(1438) in the substrate binding site could be targeted by
      Delta(12)-prostaglandin J(2) (Delta(12)-PGJ(2)), a cyclopentenone prostaglandin
      (CyPG) derived from PGD(2). We demonstrate here the ability of CyPGs to inhibit
      p300 HAT-dependent acetylation of histone H3. A cell-based assay system clearly
      showed that the alpha,beta-unsaturation in the cyclopentenone ring of Delta(12)
      PGJ(2) was crucial for the inhibitory activity, while the 9,10-dihydro-15-deoxy
      Delta(12,14)-PGJ(2), which lacks the electrophilic carbon (at carbon 9), was
      ineffective. Molecular docking studies suggested that Delta(12)-PGJ(2) places the
      electrophilic carbon in the cyclopentenone ring well within the vicinity of
      Cys(1438) of p300 to form a covalent Michael adduct. Site-directed mutagenesis of
      the p300 HAT domain, peptide competition assay involving p300 wild type and
      mutant peptides, followed by mass spectrometric analysis confirmed the covalent
      interaction of Delta(12)-PGJ(2) with Cys(1438). Using biotinylated derivatives of
      Delta(12)-PGJ(2) and 9,10-dihydro-15-deoxy-Delta(12,14)-PGJ(2), we demonstrate
      the covalent interaction of Delta(12)-PGJ(2) with the p300 HAT domain, but not
      the latter. In agreement with the in vitro filter binding assay, CyPGs were also
      found to inhibit H3 histone acetylation in cell-based assays. In addition,
      Delta(12)-PGJ(2) also inhibited the acetylation of the HIV-1 Tat by recombinant
      p300 in in vitro assays. This study demonstrates, for the first time, that
      Delta(12)-PGJ(2) inhibits p300 through Michael addition, where alpha,beta
      unsaturated carbonyl function is absolutely required for the inhibitory activity.

PMID- 22141354
TI  - Effect of robotic manipulation on unidirectional barbed suture integrity:
      evaluation of tensile strength and sliding force.
AB  - BACKGROUND AND PURPOSE: One of the more challenging portions of robot-assisted
      radical prostatectomy (RARP) is the urethrovesical anastomosis. Because of this,
      a unidirectional absorbable barbed suture (V-Loc(TM)) has been used to complete
      the anastomosis with better efficiency and less tension. The effect of robotic
      needle driver manipulation on barbed suture is unknown. Therefore, the aim of
      this study is to determine whether robotic manipulation decreases the tensile
      strength and peak sliding force of V-Loc barbed suture. MATERIALS AND METHODS:
      Fifty-six V-Loc sutures were compared with 56 Maxon sutures. All sutures were 3-0
      caliber. Half of the sutures in each group were manipulated with a da Vinci((r))
      robot large needle driver five times over a 5 cm length of suture. The other half
      was not manipulated. Breaking force was determined by placing sutures in a Bose
      ElectroForce load testing device. For sliding force testing, 28 V-Loc sutures
      were manipulated in the same fashion and compared with 28 nonmanipulated V-Loc
      sutures. Peak force needed to make the suture slip backward in porcine small
      intestine was determined to be the sliding force. Scanning electron microscopy of
      the barbs before and after robotic manipulation was also performed. RESULTS: The
      mean difference in breaking forces for manipulated vs nonmanipulated Maxon
      sutures was 4.52 N (P=0.004). The mean difference in breaking forces for
      manipulated vs nonmanipulated V-Loc sutures was 1.30 N (P=0.046). The manipulated
      V-Loc group demonstrated a lower peak sliding force compared with the
      nonmanipulated group (0.76 vs 0.88 N, P=0.199). Electron microscopy revealed
      minor structural damage to the barbs and suture. CONCLUSION: Tensile strength and
      peak sliding force of V-Loc suture is decreased by robotic manipulation. This is
      likely because of structural damage to the suture and barbs. This structural
      damage, however, is likely not clinically significant.

PMID- 22141355
TI  - Oral mucosa tissue response to titanium cover screws.
AB  - BACKGROUND: Titanium is the most widely used metal in dental implantology. The
      release of particles from metal structures into the biologic milieu may be the
      result of electrochemical processes (corrosion) and/or mechanical disruption
      during insertion, abutment connection, or removal of failing implants. The aim of
      the present study is to evaluate tissue response of human oral mucosa adjacent to
      titanium cover screws. METHODS: One hundred fifty-three biopsies of the supra
      implant oral mucosa adjacent to the cover screw of submerged dental implants were
      analyzed. Histologic studies were performed to analyze epithelial and connective
      tissue as well as the presence of metal particles, which were identified using
      microchemical analysis. Langerhans cells, macrophages, and T lymphocytes were
      studied using immunohistochemical techniques. The surface of the cover screws was
      evaluated by scanning electron microscopy (SEM). RESULTS: Forty-one percent of
      mucosa biopsies exhibited metal particles in different layers of the section
      thickness. Particle number and size varied greatly among specimens.
      Immunohistochemical study confirmed the presence of macrophages and T lymphocytes
      associated with the metal particles. Microchemical analysis revealed the presence
      of titanium in the particles. On SEM analysis, the surface of the screws
      exhibited depressions and irregularities. CONCLUSIONS: The biologic effects seen
      in the mucosa in contact with the cover screws might be associated with the
      presence of titanium or other elements, such as aluminum or vanadium. The
      potential long-term biologic effects of particles on soft tissues adjacent to
      metallic devices should be further investigated because these effects might
      affect the clinical outcome of the implant.

PMID- 22141356
TI  - The subgingival microbiota of Papillon-Lefevre syndrome.
AB  - BACKGROUND: There is little information about the microbiologic profiles of
      periodontal lesions in Papillon-Lefevre syndrome (PLS) and the significance of
      bacteria in the pathogenesis of periodontitis in these patients. This
      comprehensive analysis of the subgingival microbiota in patients with PLS used
      16S ribosomal RNA (rRNA) clonal analysis and the 16S rRNA-based Human Oral
      Microbe Identification Microarray (HOMIM). METHODS: Thirteen patients with PLS
      from seven unrelated families volunteered for this microbiologic study.
      Subgingival plaque was collected with sterile paper points from multiple sites
      with >=5 mm probing depth, and whole genomic DNA was extracted. The 16S rRNA
      genes were amplified, cloned, and sequenced. The samples were then probed for
      ~300 predominant oral bacterial species using the HOMIM. RESULTS: The most
      commonly detected phylotypes in the clonal analysis were Gemella morbillorum,
      Gemella haemolysans, Granulicatella adiacens, Lachnospiraceae OT 100 (EI074),
      Parvimonas micra, Selenomonas noxia, and Veillonella parvula. As a group,
      streptococci were commonly detected in these individuals. In the HOMIM analysis,
      a total of 170 bacterial species/phylotypes were detected, with a range of 40 to
      80 species per patient with PLS. Of these, 12 bacterial species were detected in
      medium to high levels in >=50% of the individuals. The high-frequency strains
      were clustered into eight groups: Aggregatibacter actinomycetemcomitans,
      Campylobacter spp., Capnocytophaga granulosa, G. morbillorum, P. micra,
      Porphyromonas endodontalis, Streptococcus spp., and Tannerella forsythia.
      CONCLUSIONS: The subgingival microbiota in PLS is diverse. Periodontal pathogens
      commonly associated with chronic and aggressive periodontitis and opportunistic
      pathogens may be associated with the development of severe periodontitis in
      patients with PLS.

PMID- 22141357
TI  - Serum plasminogen activator inhibitor-1 and tumor necrosis factor-alpha levels in
      obesity and periodontal disease.
AB  - BACKGROUND: Several studies have shown a possible association between periodontal
      disease and obesity. The aim of this study is to evaluate serum plasminogen
      activator inhibitor 1 (PAI-1), tumor necrosis factor-alpha (TNF-alpha), and high
      sensitivity C-reactive protein (hsCRP) levels in the association between obesity
      and periodontal disease. METHODS: Two hundred individuals participated in this
      study. Body mass index (BMI), waist-to-hip ratio, plasma triglyceride (TRG),
      total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol (HDL-C), fasting blood glucose (FBG), hsCRP, TNF-alpha, PAI-1, and
      periodontal parameters (including plaque index [PI], probing depth [PD], clinical
      attachment level [CAL], and percentage of sites with bleeding on probing) were
      evaluated. RESULTS: The groups with BMI >= 25 had higher median values for FBG,
      TRG, hsCRP, PAI-1, PI, and CAL than did the groups with a BMI < 25 (P <0.01).
      Serum TRG levels were positively correlated with PI, PD, and CAL. There were
      negative associations between clinical periodontal parameters and HDL-C. There
      were statistically significant correlations between PAI-1 and clinical
      periodontal parameters (PI, PD, and CAL). CONCLUSION: Serum PAI-1 levels may play
      an important role in the association between periodontal disease and obesity.

PMID- 22141358
TI  - A randomized clinical trial to evaluate and compare implants placed in augmented
      versus non-augmented extraction sockets: 3-year results.
AB  - BACKGROUND: The alveolar ridge undergoes reabsorption and atrophy subsequent to
      tooth removal and thus exhibits a wide range of dimensional changes. Preservation
      of the alveolar crest after tooth extraction is essential to enhance the surgical
      site before implant fixture placement. The aim of this randomized clinical study
      is to investigate and compare the need for additional augmentation procedures at
      implant insertion, as well as the success rate and marginal bone loss for
      implants placed in the grafted sites versus those placed in naturally healed
      sites. METHODS: Forty patients with >=1 hopeless tooth were randomly allocated
      to: 1) a test group, receiving extraction and grafting corticocancellous porcine
      bone; and 2) a control group, receiving extraction without any graft. After 7
      months of healing, implants were inserted in each of the sites. The implants were
      submerged and loaded after 4 months with metal-ceramic rehabilitation. The follow
      up included evaluation of implant diameter and length, the need for additional
      augmentation procedures at implant placement, implant failure, and marginal bone
      level changes. All patients were followed over a 3-year period. RESULTS: One
      implant failed in the control group at the second stage of surgery (6 months
      after placement); one implant failed in the test group after 2 years of loading.
      The cumulative implant success rate at the 3-year follow-up visit reached 95% for
      both groups. No statistically significant differences were detected for marginal
      bone changes between the two groups. CONCLUSIONS: It was concluded that implants
      placed into grafted extraction sockets exhibited a clinical performance similar
      to implants placed into non-grafted sites in terms of implant survival and
      marginal bone loss. However, grafted sites allowed placement of larger implants
      and required less augmentation procedures at implant placement when compared to
      naturally healed sites.

PMID- 22141359
TI  - Oral care practices and A1c among youth with type 1 and type 2 diabetes.
AB  - BACKGROUND: Periodontal treatment is associated with lower hemoglobin A1c in
      individuals with diabetes, but the relationship between oral hygiene practices
      and A1c among youth with diabetes is understudied. METHODS: This study evaluates
      the cross-sectional relationships among oral health habits, reported oral
      conditions, and A1c and control of diabetes among a subset of youth with diabetes
      enrolled in the SEARCH for Diabetes in Youth study in South Carolina. Oral
      hygiene practices were determined by questionnaire, and periodontal bone loss was
      defined as alveolar bone loss >=3 mm on >=1 permanent tooth site on preexisting
      bitewing radiographs. A1c was considered controlled if individuals were aged <=6
      years with A1c <8.5%; aged 7 to 11 years with A1c <8.0%; aged 12 to 18 years with
      A1c <7.5%; and aged >=19 years with A1c <7.0%. RESULTS: Among 155 participants,
      68% brushed their teeth no less than once daily, 84% flossed, and 70% rinsed,
      respectively, less than once a week. Diabetes control was associated with
      toothbrushing (>=1 time daily [odds ratio (OR) = 3.10; 95% confidence interval
      (CI) = 1.26 to 7.62] and using mouthrinse at least once weekly (OR = 3.33; 95% CI
      = 1.30 to 8.54) after multivariate adjustment. Periodontal bone loss was three
      times more common among those with dry mouth (OR = 3.05; 95% CI = 1.07 to 8.70).
      CONCLUSIONS: Clinicians should be aware that children with diabetes tend to have
      poor oral hygiene practices. Dry mouth may indicate periodontal bone loss in
      children with diabetes.

PMID- 22141360
TI  - Adsorption of enamel matrix proteins to a bovine-derived bone grafting material
      and its regulation of cell adhesion, proliferation, and differentiation.
AB  - BACKGROUND: The use of various combinations of enamel matrix derivative (EMD) and
      grafting materials has been shown to promote periodontal wound
      healing/regeneration. However, the downstream cellular behavior of periodontal
      ligament (PDL) cells and osteoblasts has not yet been studied. Furthermore, it is
      unknown to what extent the bleeding during regenerative surgery may influence the
      adsorption of exogenous proteins to the surface of bone grafting materials and
      the subsequent cellular behavior. In the present study, the aim is to test EMD
      adsorption to the surface of natural bone mineral (NBM) particles in the presence
      of blood and determine the effect of EMD coating to NBM particles on downstream
      cellular pathways, such as adhesion, proliferation, and differentiation of
      primary human osteoblasts and PDL cells. METHODS: NBM particles were precoated in
      various settings with EMD or human blood and analyzed for protein adsorption
      patterns via fluorescent imaging and high-resolution immunocytochemistry with an
      anti-EMD antibody. Cell attachment and cell proliferation were quantified using
      fluorescent double-stranded DNA-binding dye. Cell differentiation was analyzed
      using real-time polymerase chain reaction for genes encoding runt-related
      transcription factor 2, alkaline phosphatase (ALP), osteocalcin (OC), and
      collagen1alpha1 (COL1A1), and mineralization was assessed using red dye staining.
      RESULTS: Analysis of cell attachment and cell proliferation revealed
      significantly higher osteoblast and PDL cell attachment on EMD-coated surfaces
      when compared with control and blood-coated surfaces. EMD also stimulated release
      of growth factors and cytokines, including bone morphogenetic protein 2 and
      transforming growth factor beta1. Moreover, there were significantly higher mRNA
      levels of osteoblast differentiation markers, including COL1A1, ALP, and OC, in
      osteoblasts and PDL cells cultured on EMD-coated NBM particles. CONCLUSION: The
      present results suggest that 1) EMD enhances osteoblast and PDL cell attachment,
      proliferation, and differentiation on NBM particles, and 2) blood contamination
      of the grafting material before mixing with EMD may inhibit EMD adsorption.

PMID- 22141361
TI  - Bacterial lysine decarboxylase influences human dental biofilm lysine content,
      biofilm accumulation, and subclinical gingival inflammation.
AB  - BACKGROUND: Dental biofilms contain a protein that inhibits mammalian cell
      growth, possibly lysine decarboxylase from Eikenella corrodens. This enzyme
      decarboxylates lysine, an essential amino acid for dentally attached cell
      turnover in gingival sulci. Lysine depletion may stop this turnover, impairing
      the barrier to bacterial compounds. The aims of this study are to determine
      biofilm lysine and cadaverine contents before oral hygiene restriction (OHR) and
      their association with plaque index (PI) and gingival crevicular fluid (GCF)
      after OHR for 1 week. METHODS: Laser-induced fluorescence after capillary
      electrophoresis was used to determine lysine and cadaverine contents in dental
      biofilm, tongue biofilm, and saliva before OHR and in dental biofilm after OHR.
      RESULTS: Before OHR, lysine and cadaverine contents of dental biofilm were
      similar and 10-fold greater than in saliva or tongue biofilm. After 1 week of
      OHR, the biofilm content of cadaverine increased and that of lysine decreased,
      consistent with greater biofilm lysine decarboxylase activity. Regression
      indicated that PI and GCF exudation were positively related to biofilm lysine
      after OHR, unless biofilm lysine exceeded the minimal blood plasma content, in
      which case PI was further increased but GCF exudation was reduced. CONCLUSIONS:
      After OHR, lysine decarboxylase activity seems to determine biofilm lysine
      content and biofilm accumulation. When biofilm lysine exceeds minimal blood
      plasma content after OHR, less GCF appeared despite more biofilm. Lysine appears
      important for biofilm accumulation and the epithelial barrier to bacterial
      proinflammatory agents. Inhibiting lysine decarboxylase may retard the increased
      GCF exudation required for microbial development and gingivitis.

PMID- 22141362
TI  - Unexpected anomeric selectivity of a 1-C-arylglycal donor in Kdo glycoside
      synthesis.
AB  - A novel class of 1-C-arylglycals was developed and subjected to N-iodosuccinimide
      mediated glycosylations with alcohols. Unexpectedly, all reactions provided 2
      iodo-beta-D-ketopyranosides in high yields and excellent stereoselectivity. After
      removal of the 2-iodide by radical conditions, the aryl group was smoothly
      oxidized to provide the corresponding beta-Kdo glycosides. A mechanism for the
      stereoselective formation of beta-D-ketopyranosides was proposed, which was
      supported by evidence from X-ray crystallography.

PMID- 22141363
TI  - Estrogen receptor gene polymorphisms in a group of postmenopausal Turkish women:
      association with bone mineral density.
AB  - OBJECTIVE: To evaluate the frequency of the estrogen receptor (ER) gene PvuII and
      XbaI polymorphisms and their associations with bone mineral density (BMD) in a
      group of postmenopausal Turkish women. DESIGN: A total of 125 healthy
      postmenopausal women and 125 premenopausal healthy young women as controls were
      included in the study. The PvuII and XbaI polymorphisms in the ER gene were
      studied by the polymerase chain reaction-restriction fragment length polymorphism
      method. The BMD of the lumbar vertebrae and femoral neck were measured by dual
      energy X-ray absorptiometry. RESULTS: The frequencies of the ERalpha PVuII
      genotypes PP, Pp and pp were 20%, 54.4% and 25.6% in premenopausal and 24.8%,
      44.8% and 30.4% in postmenopausal women, respectively. The frequencies of the ER
      XbaI genotypes XX, Xx, xx were 16.8%, 48.8% and 34.4% in premenopausal and 16.8%,
      48% and 35.2% in postmenopausal women, respectively. There was no difference in
      the frequencies of ER gene polymorphisms between premenopausal and postmenopausal
      women. BMD measurements were not different between ER PvuII and XbaI genotypes in
      premenopausal and postmenopausal women. CONCLUSIONS: ER gene PvuII and XbaI
      polymorphisms have no major influence on bone mineral density in our group of
      postmenopausal women.

PMID- 22141364
TI  - Evaluation of tremolite asbestos exposures associated with the use of commercial
      products.
AB  - Tremolite is a noncommercial form of amphibole mineral that is present in some
      chrysotile, talc, and vermiculite deposits. Inhalation of asbestiform tremolite
      is suspected to have caused or contributed to an increased incidence of
      mesothelioma in certain mining settings; however, very little is known about the
      magnitude of tremolite exposure that occurred at these locations, and even less
      is known regarding tremolite exposures that might have occurred during consumer
      use of chrysotile, talc, and vermiculite containing products. The purpose of this
      analysis is to evaluate the exposure-response relationship for tremolite asbestos
      and mesothelioma in high exposure settings (mining) and to develop estimates of
      tremolite asbestos exposure for various product use scenarios. Our interpretation
      of the tremolite asbestos exposure metrics reported for the Thetford chrysotile
      mines and the Libby vermiculite deposits suggests a lowest-observed-adverse
      effect level (LOAEL) for mesothelioma of 35-73 f/cc-year. Using measured and
      estimated airborne tremolite asbestos concentrations for simulated and actual
      product use, we conservatively estimated the following cumulative tremolite
      asbestos exposures: career auto mechanic: 0.028 f/cc-year; non-occupational use
      of joint compound: 0.0006 f/cc-year; non-occupational use of vermiculite
      containing gardening products: 0.034 f/cc-year; home-owner removal of Zonolite
      insulation: 0.0002 f/cc-year. While the estimated consumer tremolite exposures
      are far below the tremolite LOAELs derived herein, this analysis examines only a
      few of the hundreds of chrysotile- and talc-containing products.

PMID- 22141365
TI  - Environmental contaminant mixtures at ambient concentrations invoke a metabolic
      stress response in goldfish not predicted from exposure to individual compounds
      alone.
AB  - Environmental contaminants from wastewater and industrial or agricultural areas
      are known to have adverse effects on development, reproduction, and metabolism.
      However, reliable assessment of environmental contaminant impact at low (i.e.,
      ambient) concentrations using genomics and transcriptomics approaches has proven
      challenging. A goldfish model was used to investigate the effects of aquatic
      pollutant exposure in vivo by means of quantitative nuclear magnetic resonance
      metabolomics in multiple organs to elucidate a system-wide response. Animals were
      exposed to 4,4'-isopropylidenediphenol (Bisphenol-A, BPA), di-(2-ethylhexyl)
      phthalate (DEHP), and nonylphenol (NP). Metabolite-specific spectral analysis
      combined with pathway-driven bioinformatics indicated changes in energy and lipid
      metabolism in liver following exposure to individual contaminants and a tertiary
      mixture. A dissimilar response in testis exposed to DEHP and mixture indicates
      disrupted AMPK and cAMP signaling. Uniquely, our observations (1) suggest that
      exposure to a contaminant mixture is characterized by a stress response not
      predicted from exposure to individual contaminants, even in the absence of other
      phenotypic features and (2) demonstrate the sensitivity of metabolomics in risk
      assessment of environmental toxicant mixtures at ambient concentrations by
      detecting early stage metabolic dysregulation. These findings have general
      applicability in the assessment of "benign" compound mixtures in environmental
      and pharmaceutical development.

PMID- 22141366
TI  - Raman and X-ray investigations of ferroelectric phase transition in NH4HSO4.
AB  - Temperature-dependent Raman spectroscopy and X-ray diffraction studies have been
      carried out on NH(4)HSO(4) single crystals in the temperature range 77-298 K. Two
      structural transitions driven by the molecular ordering and change in crystal
      symmetries are observed below 263 and 143 K. These phase transitions are marked
      by the anomalies in the temperature dependence of wavenumber and fwhm of several
      internal vibrational modes. The Raman spectra and X-ray data enable us to
      understand the nature of the molecular ordering resulting in the ferroelectric
      phase below 263 K, sandwiched between two nonferroelectric phases. The crystal
      structure of the ferroelectric phase is determined correctly as Pc, which has
      been earlier solved in Ba symmetry. The temperature dependent Raman and X-ray
      results suggest that the disorder to order transition leading to lower symmetry
      below 263 K is driven by the change in HSO(4)(-) ions and that below 143 K is
      driven by the change in both HSO(4)(-) and NH(4)(+) ions.

PMID- 22141367
TI  - Characteristics of intestinal lamina propria dendritic cells in a mouse model of
      postinfectious irritable bowel syndrome.
AB  - BACKGROUND AND AIM: Postinfectious irritable bowel syndrome (PI-IBS), which
      results from inflammation has been emphasized a lot recently. Dendritic cells
      (DCs) may contribute to intestinal mucosal immune activation in the pathogenesis
      of PI-IBS. This study tested the hypothesis that phenotype and function of
      intestinal lamina propria DCs (LPDCs) changed in the development of a PI-IBS
      mouse model. METHODS: Mice infected with Trichinella spiralis underwent abdominal
      withdrawal reflex (AWR) to evaluate visceral sensitivity. LPDCs were isolated and
      purified by intestine digestion and magnetic label-based technique. Surface
      markers were analyzed by flow cytometry. Endocytic activity, mixed lymphocyte
      reaction (MLR) and chemotaxis were studied. Cytokine production of the LPDCs
      cocultured with CD4(+) T cells was determined. RESULTS: Intestinal inflammation
      resolved after 8 weeks infection with sustained visceral hyperalgesia. Surface
      markers CD86 and MHCII were lower in the acute infection group, but increased in
      the PI-IBS stage. Enhanced ability of endocytic activity and decreased abilities
      to attract and stimulate CD4(+) T cell proliferation were in the acute infection
      group. However, LPDCs in the PI-IBS stage showed weakened endocytic ability with
      enhanced abilities to attract and stimulate CD4(+) T cell proliferation.
      Cocultured LPDCs with CD4(+) T cells showed a predominant Th2 response in the
      acute infection stage, and more important roles of Th1, Th17 responses in the PI
      IBS stage. CONCLUSIONS: The hypothesis was supported that the phenotype and
      function of LPDCs changed in the development of PI-IBS, which induced the
      maintenance of intestinal mucosal immune activation and might provide a clue for
      the treatment of the disease.

PMID- 22141368
TI  - Asymptomatic carriage of malaria parasites in blood donors in Yaounde.
AB  - BACKGROUND: Malaria can be transmitted through blood transfusion, but there is
      paucity of data concerning transfusion-transmitted malaria in Cameroun.
      OBJECTIVE: To determine prevalence of malaria infection and association with
      epidemiological and clinical data obtained from donors' responses. METHODS:
      Microscopic examination of stained thick and thin blood smears for the detection,
      quantification and specification of Plasmodium sp was performed on 493 blood
      donors in two main hospitals in Yaounde during October and November 2007.
      RESULTS: Overall 6 . 5% of blood donors were detected positive for Plasmodium sp
      infection: 90 . 6% was Plasmodium falciparum and 9 . 4% was Plasmodium malariae.
      Parasite counts ranged from 80 to 800 uL(-1) with a median of 320 uL(-1). Asexual
      and sexual forms were found in 75 . 9 and 24 . 1% of cases, respectively. Age,
      sex, type of blood donor (voluntary non-remunerated vs familial/replacement) and
      fate of blood donation (selected vs discarded) did not affect the prevalence of
      malaria carriage. The lack of malaria prophylaxis as well as the manifestation of
      malaria symptoms within 2 weeks and 1 month preceding blood donation were
      significantly associated with high frequency of parasites carriage. CONCLUSION:
      Malaria parasites carriage is frequent among blood donors in Yaounde. These data
      seem to describe high-risk donor profile and may help improving blood safety
      related to transfusion-transmitted malaria in Cameroon.

PMID- 22141369
TI  - On the geometry of fluoroscopy views for cervical interlaminar epidural
      injections.
AB  - OBJECTIVES: To describe how the anatomy of the cervicothoracic vertebrae
      predicates the appropriate fluoroscopic views for confirming safe needle
      placement during the performance of interlaminar cervical epidural injections.
      METHODS AND RESULTS: Illustrations, cadaver models, and radiographic images were
      correlated and used to illustrate and derive a mathematical model to demonstrate
      the utility of a contralateral oblique fluoroscopic view during the performance
      of cervical interlaminar injections. CONCLUSIONS: When confirming needle
      placement during a cervical interlaminar epidural injection, in addition to the
      anterior-posterior fluoroscopic view, the oblique image, contralateral to the
      needle tip position, may provide superior information to that afforded by a
      lateral view.

PMID- 22141370
TI  - The role of maternal factors in sibling relationship quality: a multilevel study
      of multiple dyads per family.
AB  - BACKGROUND:   Although many children grow up with more than one sibling, we do
      not yet know if sibling dyads within families show similarities to one another on
      sibling affection and hostility. In the present study the hypotheses were tested
      that (a) there will be significant between family variation in change in sibling
      affection and hostility and (b) this between family variation will be explained
      by maternal affective climate, operationalized as positive and negative ambient
      parenting, differential parenting and maternal malaise. METHODS:   A general
      population sample of families with single and multiple sibling dyads were visited
      twice, 2 years apart. Up to 2 children in a family acted as informants; 253
      relationships were rated in 118 families. A cross-classified, multilevel model
      was fit to separate between-family and within-family variance in sibling
      relationships while simultaneously controlling for informant and partner
      influences. RESULTS:   Thirty-seven percent of the variance in change in sibling
      affection and 32% of the variance in change in sibling hostility was between
      family variance. The measured maternal affective climate including, maternal
      malaise and maternal ambient and differential hostility and affection explained
      between family differences. CONCLUSIONS:   Sibling relationship quality clusters
      in families and is partly explained by maternal affective climate.

PMID- 22141371
TI  - Bitter taster status predicts susceptibility to vection-induced motion sickness
      and nausea.
AB  - BACKGROUND: Sensitivity to bitter taste and susceptibility to nausea are both
      protective mechanisms that guard against toxin ingestion, and both these traits
      vary within and between populations. Thus, we postulated that they may have co
      evolved, such that they are associated. METHODS: Bitter taster status was
      determined in 40 subjects (13 men, 27 women) by measuring the differential
      perceived taste intensity between salt and n-propylthiouracil using a labeled
      magnitude scale; susceptibility to vection-induced motion sickness and nausea was
      assessed using an optokinetic drum, a validated multi-symptom scoring scale, and
      electrogastrography. KEY RESULTS: Taster status distribution was 25% non-tasters
      (NT), 40% tasters (T), and 35% supertasters (ST). Gender had no impact on this
      distribution, but females had a higher mean maximum symptom score than males
      (12.4 +/- 1.4 vs 7.3 +/- 2.0). Non-tasters displayed a faster and larger increase
      in mean symptom scores, had a higher percentage of subjects with high maximum
      symptom scores, and had a higher mean maximum score than T or ST, (14.8 +/- 2.6
      vs 7.1 +/- 1.8, vs 9.8 +/- 2.0). Taster status did not affect the gastric
      myoelectric frequency response to vection. CONCLUSIONS & INFERENCES: Non-tasters
      are more susceptible to vection-induced motion sickness and nausea than T or ST,
      suggesting these two traits may have co-evolved in a reciprocal manner: in
      environments where the NT trait conferred an evolutionary advantage by enabling
      intake of fruits and vegetables containing bitter, yet beneficial,
      phytonutrients, increased nausea susceptibility may have arisen to maintain
      protection against ingested toxins.

PMID- 22141372
TI  - Outcomes of retrograde intrarenal surgery compared with percutaneous
      nephrolithotomy in elderly patients with moderate-size kidney stones: a matched
      pair analysis.
AB  - PURPOSE: The aim of our study was to evaluate the outcomes of retrograde
      intrarenal surgery (RIRS) in elderly patients with stones of moderate size.
      PATIENTS AND METHODS: Between September 2008 and June 2011, a total of 28
      patients over 65 years of age with single renal stones that measured 1.5 to 3 cm
      were treated with RIRS. The outcomes of these patients were compared with those
      of the patients who underwent percutaneous nephrolithotomy (PCNL) using matched
      pair analysis (1:1 scenario). The matching parameters were the size and location
      of the stone as well as age, sex, body mass index, degree of hydronephrosis,
      presence of previous shockwave lithotripsy, and open surgery. SPSS version 16 was
      used for statistical analysis. RESULTS: Stone-free rates after a single procedure
      were achieved in 82.1% of patients for the RIRS and 92.8% of patients for the
      PCNL group. The second flexible ureterorenoscopy procedure was performed for five
      patients in the RIRS group. Finally, stone-free rates during the third month of
      the follow-up period were 92.8% in the RIRS group and 96.4% in the PCNL group.
      The mean operative time per patient was 64.5 +/- 20.9 minutes in the RIRS group
      after a total of 33 procedures, while it was 40.7 +/- 10.7 minutes in the PCNL
      groups (P<0.0001). The overall complication rates for the RIRS and PCNL groups
      were 7.1% and 10.7%, respectively. Blood transfusions were needed in two patients
      in the PCNL group. Hospitalization time was significantly shorter in the RIRS
      group (26.5 +/- 10.6 h per patient vs 60.0 +/- 28.8 h; P<0.0001). In both groups,
      stones were most frequently composed of calcium oxalate (68.4% in the RIRS group
      and 77.7% in the PCNL group). CONCLUSION: RIRS has a low complication rate and
      represents a safe and effective treatment alternative in selected geriatric
      patients with kidney stones of moderate size.

PMID- 22141373
TI  - Prospective study of the PerigeeTM system for treatment of cystocele - our five
      year experience.
AB  - OBJECTIVES: The PerigeeTM transobturator cystocoele repair system (AMS) was
      designed and first used in Townsville, Australia. In this study, we are reporting
      our five-year experience with the PerigeeTM system in the management of
      cystocoele stage III and above. METHODS: Women who underwent surgery with the
      PerigeeTM system between March 2004 and June 2008 were reviewed. Women who
      consecutively presented to our clinic with a stage III cystocoele or above were
      given information regarding the PerigeeTM mesh surgery. Those who consented were
      included in our study. The study involved a POPQ assessment pre- and post
      operatively at six weeks, three months, six months, 12 months and subsequently
      biannually. RESULTS: A total of 376 women underwent surgery with the PerigeeTM
      system between March 2004 and June 2008, of which 26 were lost to follow-up. The
      anatomical success rate for the device was 94.3%, and there were no life
      threatening complications with the procedure. 39 (11.1%) of women were found to
      have small mesh extrusion through the vagina, and 20 (5.7%) had recurrence of
      stage II cystocoele. Of the subset of women analysed, 45.1% reported no sexual
      dysfunction, 40.9% reported improvement in sexual function, while 4.1% reported
      worsening of dyspareunia. CONCLUSION: In this five-year experience, the PerigeeTM
      system is deemed safe with an acceptable recurrence risk rate and complication
      rate. Further randomised controlled trials comparing PerigeeTM system with
      traditional anterior colporrhaphy should be performed to evaluate mesh-based
      surgery safety and efficacy for level one evidence.

PMID- 22141374
TI  - Ethanol production from acetate: a path to the economically viable bioethanol.

PMID- 22141375
TI  - Dermatological testing of an improved apertured film surface for feminine hygiene
      pads.
AB  - CONTEXT: Apertured polyethylene films (AF) have been used as a surface for
      sanitary pads for decades because they are compatible with the skin and keep the
      pad surface drier. A modified film (AF-plus) with improved fluid handling and a
      smoother, suppler texture has been developed. We hypothesized that these changes
      would improve both performance and skin compatibility. However, distinguishing
      the skin effects of materials that are inherently mild is a challenge.
      OBJECTIVES: (i) To compare the skin irritation potential of pads with AF-plus
      modified film relative to the standard AF film and (ii) to assess the potential
      for the AF-plus film to induce delayed contact hypersensitivity. MATERIALS AND
      METHODS: Pads bearing the AF-plus film were compared to pads with the standard AF
      film in a behind-the-knee (BTK) test, which assesses the combination of chemical
      irritation and frictional effects of materials applied to the popliteal fossa
      under a semi-occlusive bandage. Erythema on the skin surface was scored with the
      naked eye and subsurface tissue erythema was visualized and scored using cross
      polarized illumination. Skin dryness was scored with the naked eye only. One
      sided statistical evaluations were performed to test the hypothesis of AF-plus
      film superiority. The potential of the AF-plus film to induce delayed contact
      hypersensitivity was assessed by a human repeat insult patch test (HRIPT).
      RESULTS: Pads with the AF-plus surface were significantly milder to skin in the
      BTK test, producing lower levels of both surface and subsurface tissue erythema.
      Moreover, subjects with preexisting erythema on the skin surface at study start
      developed comparatively less erythema over the course of the study overall with
      the AF-plus pad compared to the AF pad. No significant difference in skin dryness
      was observed between product groups. The AF-plus pad showed no evidence of
      inducing delayed contact hypersensitivity. CONCLUSIONS: The AF-plus pad was
      superior to the AF pad in terms of skin mildness as discerned by objectively
      scored surface and subsurface tissue erythema. In subjects with preexisting
      erythema, the AF-plus pad appeared to contribute less to the further development
      of inflammation under the test conditions. Given the compositional similarities
      in the two films, the results could point to more limited contribution of the AF
      plus film to skin friction, one of the factors simulated by the BTK test
      protocol.

PMID- 22141376
TI  - Papular, profuse, and precocious keratosis pilaris.
AB  - Keratosis pilaris (KP) is a frequent and benign condition in children
      characterized by the presence of rough, follicular papules and varying degrees of
      erythema. Different variants have been described, including simple KP and red KP.
      Between September 2007 and October 2010, 11 children with profuse and precocious
      KP seen at the department of pediatric dermatology were included. They defined an
      underemphasized clinical variant of childhood KP: the papular, profuse, and
      precocious KP characterized by early age of onset (<18 mos), extensive
      involvement of the limbs and cheeks, and papular nature of lesions. No clinical
      association has been found. The main complication was episodes of folliculitis.
      Diagnosis was delayed for all patients. Treatment is difficult, but association
      between emollient and keratolytic agents can provide some help.

PMID- 22141377
TI  - Home care for older people in Sweden: a universal model in transition.
AB  - One aspect of universalism in Swedish eldercare services is that publicly
      financed and publicly provided services have been both affordable for the poor
      and attractive enough to be preferred by the middle class. This article
      identifies two trends in home care for older people in Sweden: a decline in the
      coverage of publicly funded services and their increasing marketisation. We
      explore the mechanisms behind these trends by reviewing policy documents and
      official reports, and discuss the distributional consequences of the changes by
      analysing two data sets from Statistics Sweden: the Swedish Level of Living
      surveys from 1988/1989 and 2004/2005 and a database on all users of tax
      deductions on household and care services in 2009. The analysis shows that the
      decline of tax-funded home care is not the result of changing eldercare
      legislation and was not intended by national policy-makers. Rather the decline
      was caused by a complex interplay of decision-making at central and local levels,
      resulting in stricter municipal targeting. The trend towards marketisation has
      been more clearly intended by national policy-makers. Legislative changes have
      opened up tax-funded services to private provision, and a customer-choice
      (voucher) model and a tax deduction for household- and care services have been
      introduced. As a result of declining tax-funded home-care services, older persons
      with lower education increasingly receive family care, while those with higher
      education are more likely to buy private services. The combination of income
      related user fees, customer-choice models and the tax deduction has created an
      incentive for high-income older persons to turn to the market instead of using
      public home-care services. Thus, Swedish home care, as a universal welfare
      service, is now under threat and may become increasingly dominated by groups with
      less education and lower income which, in turn, could jeopardise the quality of
      care.

PMID- 22141378
TI  - Evaluation of melt rheology of lactose-filled polyethylene glycol composites by
      means of capillary rheometery.
AB  - In this study melt rheological behavior of lactose-filled polyethylene glycol
      (PEG) composites as a low melting polymeric carrier for controlled release drugs
      was investigated using a capillary rheometer. The effect of lactose concentration
      and process variables such as temperature and ram speed on the flow behavior of
      PEG has been studied. The composites were found to be shear thinning in behavior
      when extruded, and the results were well described by power-law model in each
      case. Stronger shear thinning behavior was observed by raising the filler
      concentration and decreasing the temperature, while the flow index has been
      decreased. In all compositions a significant increase in shear viscosity was
      found by an increase in the filler content. In fact, shear viscosity increased
      linearly by weight fraction of filler, but there was a dramatic increase after
      the filler content raised above 20 wt% of lactose which might be the result of
      the strong interaction among filler particles. Furthermore, decreasing the
      process temperature resulted in an increase in shear viscosity, and the
      temperature dependence of shear viscosity decreased as the shear rate increased.
      The extensional viscosity of composites was calculated in each case. The results
      showed that the ratio of the extensional viscosity to shear viscosity was in the
      range of 500-1200.

PMID- 22141379
TI  - Surgical nurses' perceptions of ethical dilemmas, moral distress and quality of
      care.
AB  - AIM: To describe surgical nurses' perceived levels of ethical dilemmas, moral
      distress and perceived quality of care and the associations among them.
      BACKGROUND: Nurses are committed to providing quality care. They can experience
      ethical dilemmas and moral distress while providing patient care. Little research
      has focused on the effect of moral distress or ethical dilemmas on perceived
      quality of care. DESIGN: Descriptive, cross-sectional study. METHOD: After
      administration and institutional Research Ethics Committee approval, a researcher
      requested 119 surgical nurses working in two Israeli hospitals to fill out three
      questionnaires (personal background characteristics; Ethical Dilemmas in Nursing
      and Quality of Nursing Care). Data collection took place from August 2007 to
      January 2008. RESULTS: Participant mean age was 39.7 years. The sample consisted
      mostly of women, Jewish and married staff nurses. The majority of nurses reported
      low to moderate levels of ethical dilemma frequency but intermediate levels of
      ethical dilemma intensity. Frequency of ethical dilemmas was negatively
      correlated with level of nursing skill, meeting patient's needs and total quality
      of care. No important correlations were found between intensity of ethical
      dilemmas and quality of care. CONCLUSIONS: Levels of ethical dilemma frequency
      were higher than intensity. Nurses tended to be satisfied with their level of
      quality of care. Increased frequency of ethical dilemmas was associated with some
      aspects of perceived quality of care. RELEVANCE TO CLINICAL PRACTICE: Quality of
      care is related to ethical dilemmas and moral distress among surgical nurses.
      Therefore, efforts should be made to decrease the frequency of these feelings to
      improve the quality of patient care.

PMID- 22141380
TI  - Ethanol exposure during pregnancy persistently attenuates cranially directed
      blood flow in the developing fetus: evidence from ultrasound imaging in a murine
      second trimester equivalent model.
AB  - BACKGROUND: Ethanol (EtOH) consumption during pregnancy can lead to fetal growth
      retardation, mental retardation, and neurodevelopmental delay. The fetal brain
      initiates neurogenesis and vasculogenesis during the second trimester, and
      depends on maternal-fetal circulation for nutrition and growth signals. We used
      high-resolution in vivo ultrasound imaging to test the hypothesis that EtOH
      interferes with fetal brain-directed blood flow during this critical
      developmental period. METHODS: Pregnant mice were lightly anesthetized on
      gestational day 12 with an isoflurane/oxygen mixture. We assessed the effect of
      single and repeated binge-like maternal EtOH exposures at 3 g/kg, administered by
      intragastric gavage or intraperitoneal injection, on maternal circulation and
      fetal umbilical, aortic, internal carotid, and middle cerebral arterial
      circulation. RESULTS: Binge maternal EtOH exposure, regardless of exposure route,
      significantly reduced fetal arterial blood acceleration and velocity time
      integral (VTI), from umbilical to cerebral arteries, without a change in fetal
      heart rate and resistivity indices. Importantly a single maternal binge EtOH
      exposure induced persistent suppression of fetal arterial VTI for at least 24
      hours. Repeated binge episodes resulted in a continuing and persistent
      suppression of fetal VTI. Qualitative assessments showed that maternal EtOH
      exposure induced oscillatory, nondirectional blood flow in fetal cerebral
      arteries. Maternal cardiac and other physiological parameters remained unaltered.
      CONCLUSIONS: These data show that binge-type maternal EtOH exposure results in
      rapid and persistent loss of blood flow from the umbilical artery to the fetal
      brain, potentially compromising nutrition and the maternal/fetal endocrine
      environment during a critical period for neuron formation and angiogenesis in the
      maturing brain.

PMID- 22141383
TI  - Epigenetic-based therapies in cancer: progress to date.
AB  - Epigenetic gene silencing is a hallmark of cancer cells. Two important types of
      epigenetic changes are DNA methylation and histone modification. These
      modifications are catalysed by DNA methyltransferases (DNMTs) and histone
      deacetylases (HDACs), resulting in chromatin structure changes and gene
      inactivation. Interestingly, inhibition of these enzymes is known to induce
      differentiation or apoptosis of cancer cells. Therefore, DNMTs and HDACs have
      become attractive therapeutic targets. In recent years, many different DNMT and
      HDAC inhibitors have been developed, and multiple molecular mechanisms through
      which these agents exert anti-cancer effects have been identified. While a large
      number of clinical trials are ongoing, hypomethylating agents and HDAC inhibitors
      seem to be promising for treating several types of cancer. Moreover, developing
      effective strategies of combining epigenetic therapy with conventional
      chemotherapy will be one of the major challenges in the future. We briefly review
      current advances in epigenetic therapies with a focus on recently reported
      clinical trials.

PMID- 22141386
TI  - Belimumab: in systemic lupus erythematosus.
AB  - Belimumab is a fully human recombinant IgG1lambda monoclonal antibody that
      inhibits the binding of soluble B lymphocyte stimulator to B cells and hence
      prevents the survival and differentiation of selected B-cell subsets. It is
      available in the US, the EU and Canada for the treatment of adult patients with
      active, autoantibody-positive systemic lupus erythematosus (SLE) with a high
      degree of disease activity despite receiving standard therapy. At 52 weeks, a
      significantly greater proportion of belimumab 10 mg/kg than placebo recipients
      experienced a response as assessed by the SLE Responder Index (primary endpoint)
      in the randomized, double-blind, multinational, phase III BLISS-52 and BLISS-76
      trials in patients with active seropositive SLE receiving standard therapy. A
      significantly greater proportion of belimumab than placebo recipients achieved a
      >=4 point reduction in the SELENA-SLEDAI score at week 52 in both BLISS trials.
      However, the SLE Responder Index response rate was not significantly different
      between belimumab and placebo at 76 weeks in BLISS-76. Belimumab was generally
      well tolerated in the BLISS trials. During the double-blind periods of these
      trials and the phase II trial, twice as many deaths were reported with belimumab
      than placebo (six vs three). There were no meaningful differences between the
      incidence of serious infections and malignancies with belimumab or placebo.

PMID- 22141384
TI  - Triazole antifungal agents in invasive fungal infections: a comparative review.
AB  - Invasive fungal disease continues to be a problem associated with significant
      morbidity and high mortality in immunocompromised and, to a lesser extent,
      immunocompetent individuals. Triazole antifungals have emerged as front-line
      drugs for the treatment and prophylaxis of many systemic mycoses. Fluconazole
      plays an excellent role in prophylaxis, empirical therapy, and the treatment of
      both superficial and invasive yeast fungal infections. Voriconazole is strongly
      recommended for pulmonary invasive aspergillosis. Posaconazole shows a very wide
      spectrum of activity and its primary clinical indications are as salvage therapy
      for patients with invasive aspergillosis and prophylaxis for patients with
      neutropenia and haematopoietic stem-cell transplant recipients. Itraconazole also
      has a role in the treatment of fungal skin and nail infections as well as
      dematiaceous fungi and endemic mycoses. Fluconazole and voriconazole are well
      absorbed and exhibit high oral bioavailability, whereas the oral bioavailability
      of itraconazole and posaconazole is lower and more variable. Posaconazole
      absorption depends on administration with a high-fat meal or nutritional
      supplements. Itraconazole and voriconazole undergo extensive hepatic metabolism
      involving the cytochrome P450 system. The therapeutic window for triazoles is
      narrow, and inattention to their pharmacokinetic properties can lead to drug
      levels too low for efficacy or too high for good tolerability or safety. This
      makes these agents prime candidates for therapeutic drug monitoring (TDM). Target
      drug concentrations for voriconazole and itraconazole should be >1 MUg/mL and for
      posaconazole >1.5 MUg/mL for treatment. Blood should be drawn once the patient
      reaches steady state, which occurs after 5 and 7 days of triazole therapy.
      Routine TDM of fluconazole is not required given its highly favourable
      pharmacokinetic profile and wide therapeutic index. The aim of this review is to
      provide a brief update on the pharmacology, activity, clinical efficacy, safety
      and cost of triazole agents (itraconazole, fluconazole, voriconazole and
      posaconazole) and highlight the clinical implications of similarities and
      differences.

PMID- 22141387
TI  - Fidaxomicin: in Clostridium difficile infection.
AB  - Fidaxomicin is a first-in-class macrocyclic antibacterial that primarily
      demonstrates activity against species of clostridia, predominantly Clostridium
      difficile, while having limited or no activity against normal faecal microflora.
      Fidaxomicin is minimally absorbed following oral administration and is excreted
      almost solely in the faeces. Fidaxomicin displayed a high level of antibacterial
      activity against C. difficile in vitro, with a minimum inhibitory concentration
      required to inhibit 90% of C. difficile strains of 0.125-0.5 MUg/mL, and was ~2-
      to 8-fold more active than vancomycin or metronidazole. Fidaxomicin demonstrated
      a prolonged postantibiotic effect against C. difficile relative to vancomycin and
      metronidazole. In two randomized, double-blind, phase III trials, oral
      fidaxomicin 200 mg every 12 hours for 10 days was no less effective than oral
      vancomycin 125 mg every 6 hours for 10 days in the treatment of C. difficile
      infection, based on noninferiority analyses of clinical cure rates (primary
      endpoint). Fidaxomicin therapy was associated with a significantly lower rate of
      recurrence, as well as a significantly higher rate of global cure (i.e. sustained
      clinical response; resolution of diarrhoea without recurrence) compared with
      vancomycin therapy in the two clinical trials. Fidaxomicin was generally well
      tolerated in patients with C. difficile infection, with a tolerability profile
      generally similar to that of vancomycin.

PMID- 22141385
TI  - Use of herbal medicines and nutritional supplements in ocular disorders: an
      evidence-based review.
AB  - We sought to examine the evidence regarding the use of herbal medicines and
      nutritional supplements in age-related macular degeneration (AMD), cataracts,
      diabetic retinopathy and glaucoma, and to review the ocular adverse effects of
      herbal and nutritional agents of clinical importance to ophthalmologists. We
      performed a literature search of Ovid MEDLINE and selected websites including the
      American Academy of Ophthalmology (AAO), the Centers for Disease Control and
      Prevention (CDC), the National Institutes of Health (NIH) and the World Health
      Organization (WHO). There is strong evidence supporting the use of antioxidants
      and zinc in patients with certain forms of intermediate and advanced AMD.
      However, there has been growing evidence regarding potential significant adverse
      effects associated with the AREDS (Age-Related Eye Disease Study) formula
      vitamins. Current data does not support the use of antioxidants or herbal
      medications in the prevention or treatment of cataracts, glaucoma or diabetic
      retinopathy. It is important for providers to be aware of the benefits and the
      significant potential adverse effects that have been associated with nutritional
      supplements and herbal medications, and to properly inform their patients when
      making decisions about supplementation. Further rigorous evaluation of
      nutritional supplements and herbal medicines in the treatment of eye disease is
      needed to determine their safety and efficacy.

PMID- 22141388
TI  - Celecoxib: a review of its use for symptomatic relief in the treatment of
      osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.
AB  - Celecoxib (Celebrex(r)) was the first cyclo-oxygenase (COX)-2 selective inhibitor
      (coxib) to be introduced into clinical practice. Coxibs were developed to provide
      anti-inflammatory/analgesic activity similar to that of nonselective NSAIDs, but
      without their upper gastrointestinal (GI) toxicity, which is thought to result
      largely from COX-1 inhibition. Celecoxib is indicated in the EU for the
      symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing
      spondylitis in adults. This article reviews the clinical efficacy and
      tolerability of celecoxib in these EU-approved indications, as well as
      overviewing its pharmacological properties. In randomized controlled trials,
      celecoxib, at the recommended dosages of 200 or 400 mg/day, was significantly
      more effective than placebo, at least as effective as or more effective than
      paracetamol (acetaminophen) and as effective as nonselective NSAIDs and the
      coxibs etoricoxib and lumiracoxib for the symptomatic treatment of patients with
      active osteoarthritis, rheumatoid arthritis or ankylosing spondylitis. Celecoxib
      was generally well tolerated, with mild to moderate upper GI complaints being the
      most common body system adverse events. In meta-analyses and large safety
      studies, the incidence of upper GI ulcer complications with recommended dosages
      of celecoxib was significantly lower than that with nonselective NSAIDs and
      similar to that with paracetamol and other coxibs. However, concomitant
      administration of celecoxib with low-dose cardioprotective aspirin often appeared
      to negate the GI-sparing advantages of celecoxib over NSAIDs. Although one polyp
      prevention trial noted a dose-related increase in cardiovascular risk with
      celecoxib 400 and 800 mg/day, other trials have not found any significant
      difference in cardiovascular risk between celecoxib and placebo or nonselective
      NSAIDs. Meta-analyses and database-derived analyses are inconsistent regarding
      cardiovascular risk. At recommended dosages, the risks of increased thrombotic
      cardiovascular events, or renovascular, hepatic or hypersensitivity reactions
      with celecoxib would appear to be small and similar to those with NSAIDs.
      Celecoxib would appear to be a useful option for therapy in patients at high risk
      for NSAID-induced GI toxicity, or in those responding suboptimally to or
      intolerant of NSAIDs. To minimize any risk, particularly the cardiovascular risk,
      celecoxib, like all coxibs and NSAIDs, should be used at the lowest effective
      dosage for the shortest possible duration after a careful evaluation of the GI,
      cardiovascular and renal risks of the individual patient.

PMID- 22141389
TI  - Buprenorphine 5, 10 and 20 MUg/h transdermal patch: a review of its use in the
      management of chronic non-malignant pain.
AB  - This article reviews the pharmacology, therapeutic efficacy and tolerability
      profile of the 7-day lower-dose (5, 10 and 20 MUg/h) buprenorphine transdermal
      patch (BuTrans(r), Norspan(r)) in the management of chronic non-malignant pain,
      with a focus on European labelling for the drug. Buprenorphine is a semi
      synthetic opioid analgesic that acts primarily as a partial agonist at the mu
      opioid receptor. The transdermal formulation provides continuous delivery of
      buprenorphine, resulting in relatively consistent plasma drug concentrations
      throughout the 7-day dosing interval. The analgesic efficacy of transdermal
      buprenorphine in patients with osteoarthritis of the hip and/or knee has been
      demonstrated in several randomized controlled trials, which have shown the
      formulation to be equivalent to sublingual buprenorphine, noninferior to
      prolonged-release tramadol tablets, noninferior to codeine plus paracetamol
      (acetaminophen) combination tablets (when transdermal buprenorphine was used
      together with regularly scheduled oral paracetamol) and generally superior to a
      matching transdermal placebo patch. Transdermal buprenorphine was significantly
      more effective than placebo in reducing chronic low back pain of at least
      moderate severity in two randomized, double-blind, crossover trials. Other
      clinical trials, including a randomized, double-blind, maintenance-of-analgesia
      study, have also demonstrated the analgesic efficacy of transdermal buprenorphine
      in patients with chronic non-malignant pain of various causes. In general,
      serious adverse events with transdermal buprenorphine are similar to those for
      other opioid analgesics. Transdermal buprenorphine has a ceiling effect for
      respiratory depression, and the main risk is when it is combined with other CNS
      depressants. The most frequently reported adverse events with transdermal
      buprenorphine are headache, dizziness, somnolence, constipation, dry mouth,
      nausea, vomiting, pruritus, erythema, application site pruritus and application
      site reactions. Transdermal buprenorphine was better tolerated than sublingual
      buprenorphine in a 7-week, randomized, double-blind trial in patients with
      osteoarthritis pain. Nevertheless, as with other opioids, persistence with
      transdermal buprenorphine therapy is difficult for many patients because of
      adverse events or other reasons. Thus, transdermal buprenorphine has generally
      demonstrated good efficacy and tolerability in clinical trials in chronic non
      malignant pain, providing effective background analgesia as part of pain
      management strategies for patients with osteoarthritis, low back pain and other
      persistent pain syndromes of at least moderate severity. It also has favourable
      pharmacodynamic and pharmacokinetic properties, which have beneficial clinical
      implications, most notably the convenience of once-weekly administration and no
      need for dosage adjustments in the elderly or those with compromised renal
      function, making it an opioid of choice in these patients, and a useful
      therapeutic option overall in the management of chronic non-malignant pain.

PMID- 22141390
TI  - Entecavir: a review of its use in the treatment of chronic hepatitis B in
      patients with decompensated liver disease.
AB  - The oral deoxyguanosine nucleoside analogue entecavir (Baraclude(r)) has potent
      activity against hepatitis B virus (HBV) and a high genetic barrier to
      resistance. This article reviews the clinical efficacy and tolerability of
      entecavir in the treatment of chronic hepatitis B in patients with decompensated
      liver disease, as well as summarizing its pharmacological properties. Entecavir 1
      mg/day was more effective than adefovir dipivoxil 10 mg/day in the treatment of
      patients with chronic hepatitis B and decompensated liver disease, according to
      the results of a randomized, open-label, multicentre trial. Patients were either
      nucleos(t)ide naive or lamivudine experienced. The reduction from baseline in HBV
      DNA levels at week 24 (primary endpoint) was significantly greater with entecavir
      than with adefovir dipivoxil. The proportion of patients with HBV DNA levels of
      <300 copies/mL was also significantly greater with entecavir than with adefovir
      dipivoxil at weeks 24, 48 and 96, as was the proportion of patients with ALT
      normalization. Entecavir 0.5 or 1 mg/day, tenofovir disoproxil fumarate 300
      mg/day and a fixed-dose combination of emtricitabine/tenofovir disoproxil
      fumarate 200 mg/300 mg per day were effective in the treatment of chronic
      hepatitis B in patients with decompensated liver disease, according to the 48
      week analysis of a randomized, double-blind, multicentre trial, primarily
      designed to examine tolerability endpoints. In this trial, over one-third of
      patients had received previous therapy with lamivudine for >=6 months. The
      efficacy of entecavir in treatment-naive patients with HBV-related decompensated
      cirrhosis did not significantly differ from that seen in patients with chronic
      hepatitis B or compensated cirrhosis (compensated group), according to the
      results of a prospective, nonrandomized study. After 6 or 12 months of entecavir
      treatment, there were no significant differences between the decompensated and
      compensated groups in virological, biochemical or serological endpoints. In
      patients with decompensated cirrhosis, significant improvements from baseline in
      liver function were seen after 12 months of entecavir therapy. Oral entecavir was
      generally well tolerated in patients with chronic hepatitis B and decompensated
      liver disease, with most of the reported treatment-emergent adverse events
      consistent with decompensated liver disease. In the trial primarily designed to
      examine tolerability endpoints, there was no significant difference between
      patients receiving entecavir and those receiving tenofovir disoproxil fumarate
      with or without emtricitabine in terms of the proportion of patients experiencing
      tolerability failure or the proportion of patients with confirmed increases in
      serum creatinine levels of >=0.5 mg/dL above baseline or confirmed serum
      phosphorus levels of <2.0 mg/dL at week 48 (co-primary endpoints). It has been
      suggested that the risk of lactic acidosis associated with oral nucleos(t)ide
      analogue therapy is increased in patients with highly impaired liver function.
      However, only one case of lactic acidosis was reported among entecavir recipients
      across two clinical trials in patients with chronic hepatitis B and decompensated
      liver disease. Moreover, small studies found that the risk of lactic acidosis was
      not increased in patients with chronic hepatitis B and decompensated liver
      disease who received entecavir, compared with patients with non-HBV decompensated
      liver disease. In conclusion, entecavir is a valuable agent for the first-line
      treatment of chronic hepatitis B in patients with decompensated liver disease.

PMID- 22141393
TI  - Coalition or derogation? How perceived discrimination influences intraminority
      intergroup relations.
AB  - Five studies explored how perceived societal discrimination against one's own
      racial group influences racial minority group members' attitudes toward other
      racial minorities. Examining Black-Latino relations, Studies 1a and 1b showed
      that perceived discrimination toward oneself and one's own racial group may be
      positively associated with expressed closeness and common fate with another
      racial minority group, especially if individuals attribute past experiences of
      discrimination to their racial identity rather than to other social identities
      (Study 1b). In Studies 2-5, Asian American (Studies 2, 3, and 4) and Latino
      (Study 5) participants were primed with discrimination against their respective
      racial groups (or not) and completed measures of attitudes toward Black
      Americans. Participants primed with racial discrimination expressed greater
      positivity toward and perceived similarity with Blacks than did participants who
      were not primed. These results suggest, consistent with the common ingroup
      identity model (Gaertner & Dovidio, 2000), that salient discrimination against
      one's own racial group may trigger a common "disadvantaged racial minority"
      (ingroup) identity that engenders more positive attitudes toward and feelings of
      closeness toward other racial minorities.

PMID- 22141394
TI  - Double bundle arthroscopic Anterior Cruciate Ligament reconstruction with remnant
      preserving technique using a hamstring autograft.
AB  - BACKGROUND: Preservation of the Anterior Cruciate Ligament (ACL) remnant is
      important from the biological point of view as it enhances revascularization, and
      preserves the proprioceptive function of the graft construct. Additionally, it
      may have a useful biomechanical function. Double bundle ACL reconstruction has
      been shown to better replicate the native ACL anatomy and results in better
      restoration of the rotational stability than single bundle reconstruction.
      METHODS: We used the far anteromedial (FAM) portal for creation of the femoral
      tunnels, with a special technique for its preoperative localization using three
      dimensional (3D) CT. The central anteromedial (AM) portal was used to make a
      longitudinal slit in the ACL remnant to allow visualization of the tips of the
      guide pins during anatomical creation of the tibial tunnels within the native ACL
      tibial foot print. The use of curved hemostat allow retrieval of the wire loop
      from the apertures of the femoral tunnels through the longitudinal slit in the
      ACL remnant thereby, guarding against impingement of the reconstruction graft
      against the ACL remnant as well as the roof of the intercondylar notch.
      CONCLUSION: Our technique allows for anatomical double bundle reconstruction of
      the ACL while maximally preserving the ACL remnant without the use of intra
      operative image intensifier.

PMID- 22141391
TI  - Pegylated liposomal doxorubicin: a review of its use in metastatic breast cancer,
      ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma.
AB  - Pegylated liposomal doxorubicin (CaelyxTM, Doxil(r)) represents an improved
      formulation of conventional doxorubicin, with reduced cardiotoxicity and an
      improved pharmacokinetic profile. This article reviews the efficacy and
      tolerability of pegylated liposomal doxorubicin in metastatic breast cancer,
      progressive ovarian cancer, relapsed or refractory multiple myeloma and AIDS
      related Kaposi's sarcoma, as well as summarizing its pharmacological properties.
      In three randomized, open-label, multicentre trials, monotherapy with pegylated
      liposomal doxorubicin was as effective as doxorubicin or capecitabine in the
      first-line treatment of metastatic breast cancer, and as effective as vinorelbine
      or combination mitomycin plus vinblastine in taxane-refractory metastatic breast
      cancer. Pegylated liposomal doxorubicin alone was as effective as topotecan or
      gemcitabine alone in patients with progressive ovarian cancer resistant or
      refractory to platinum- or paclitaxel-based therapy, according to the results of
      three randomized multicentre trials. In addition, in patients with progressive
      ovarian cancer who had received prior platinum-based therapy, progression-free
      survival was significantly longer with pegylated liposomal doxorubicin plus
      carboplatin than with paclitaxel plus carboplatin, according to the results of a
      randomized, open-label multicentre trial. Combination therapy with pegylated
      liposomal doxorubicin plus bortezomib was more effective than bortezomib alone in
      patients with relapsed or refractory multiple myeloma, according to the results
      of a randomized, open-label, multinational trial. Randomized multinational trials
      also demonstrated the efficacy of pegylated liposomal doxorubicin in patients
      with advanced AIDS-related Kaposi's sarcoma. Pegylated liposomal doxorubicin
      exhibited a relatively favourable safety profile compared with conventional
      doxorubicin and other available chemotherapy agents. The most common treatment
      related adverse events included myelosuppression, palmar-plantar
      erythrodysesthesia and stomatitis, although these are manageable with appropriate
      supportive measures. To conclude, pegylated liposomal doxorubicin is a useful
      option in the treatment of various malignancies, including metastatic breast
      cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma.

PMID- 22141395
TI  - Dual-modality single particle orientation and rotational tracking of
      intracellular transport of nanocargos.
AB  - The single particle orientation and rotational tracking (SPORT) technique was
      introduced recently to follow the rotational motion of plasmonic gold nanorod
      under a differential interference contrast (DIC) microscope. In biological
      studies, however, cellular activities usually involve a multiplicity of
      molecules; thus, tracking the motion of a single molecule/object is insufficient.
      Fluorescence-based techniques have long been used to follow the spatial and
      temporal distributions of biomolecules of interest thanks to the availability of
      multiplexing fluorescent probes. To know the type and number of molecules and the
      timing of their involvement in a biological process under investigation by SPORT,
      we constructed a dual-modality DIC/fluorescence microscope to simultaneously
      image fluorescently tagged biomolecules and plasmonic nanoprobes in living cells.
      With the dual-modality SPORT technique, the microtubule-based intracellular
      transport can be unambiguously identified while the dynamic orientation of
      nanometer-sized cargos can be monitored at video rate. Furthermore, the active
      transport on the microtubule can be easily separated from the diffusion before
      the nanocargo docks on the microtubule or after it undocks from the microtubule.
      The potential of dual-modality SPORT is demonstrated for shedding new light on
      unresolved questions in intracellular transport.

PMID- 22141396
TI  - Engineering botulinum neurotoxin domains for activation by toxin light chain.
AB  - Targeted secretion inhibitors (TSI) are a new class of biopharmaceuticals
      designed from a botulinum neurotoxin protein scaffold. The backbone consists of
      the 50-kDa endopeptidase light chain and translocation domain (N-terminal portion
      of the heavy chain), lacks neuronal toxicity, but retains the ability to target
      cytoplasmic soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) proteins. TSI are produced as single-chain proteins and then cleaved post
      translationally to generate functional heterodimers. Precise proteolytic cleavage
      is essential to activate the protein to a dichain form. TSI are themselves highly
      specific proteases. We have exploited this activity to create self-activating
      enzymes by replacing the native proteolytic site with a substrate SNARE peptide
      for the TSI protease. We have also created cross-activating backbones. By
      replacing the proteolytic activation site in one backbone with the substrate
      SNARE peptide for another serotype, controlled activation is achieved. SNARE
      peptides encompassing the whole of the coiled-coil region enabled complete
      activation and assembly of the dichain backbone. These engineered TSI backbones
      are capable of translocating their enzymatic domains to target intracellular
      SNARE proteins. They are also investigative tools with which to further the
      understanding of endopeptidase activity of light chain in SNARE interactions.

PMID- 22141398
TI  - Mechanism elucidation for nonstochastic femtosecond laser-induced
      ionization/dissociation: from amino acids to peptides.
AB  - Femtosecond laser-induced ionization/dissociation (fs-LID) has been demonstrated
      as a novel ion activation method for use in tandem mass spectrometry. The
      technique opens the door to unique structural information about biomolecular
      samples that is not easily accessed by traditional means. fs-LID is able to
      cleave strong bonds while keeping weaker bonds intact. This feature has been
      found to be particularly useful for the mapping of post-translational
      modifications such as phosphorylation, which is difficult to achieve by
      conventional proteomic studies. Here we investigate the laser-ion interaction on
      a fundamental level through the characterization of fs-LID spectra for the
      protonated amino acids and two series of derivatized samples. The findings are
      used to better understand the fs-LID spectra of synthetic peptides. This is
      accomplished by exploring the effects of several single-residue substitutions.

PMID- 22141397
TI  - Prolonged control of replication-competent dual- tropic human immunodeficiency
      virus-1 following cessation of highly active antiretroviral therapy.
AB  - BACKGROUND: While initiation of highly active antiretroviral therapy (HAART)
      during primary HIV-1 infection occasionally results in transient control of viral
      replication after treatment interruption, the vast majority of patients
      eventually experience a rebound in plasma viremia. RESULTS: Here we report a case
      of a patient who was started on HAART during symptomatic primary infection and
      who has subsequently maintained viral loads of < 50 copies/mL for more than nine
      years after the cessation of treatment. This patient had a high baseline viral
      load and has maintained a relatively high frequency of latently infected CD4(+) T
      cells. In addition, he does not have any known protective HLA alleles. Thus it is
      unlikely that he was destined to become a natural elite controller or suppressor.
      The mechanism of control of viral replication is unclear; he is infected with a
      CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In
      addition, his spouse, who transmitted the virus to him, developed AIDS. The
      patient's CD4(+) T cells are fully susceptible to HIV-1 infection, and he has low
      titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates.
      Furthermore, his CD8(+) T cells do not have potent HIV suppressive activity.
      CONCLUSION: This report suggests that some patients may be capable of controlling
      pathogenic HIV-1 isolates for extended periods of time after the cessation of
      HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte
      (CTL) mediated suppression that has been reported in many elite suppressors.

PMID- 22141399
TI  - GAL1-SceI directed site-specific genomic (gsSSG) mutagenesis: a method for
      precisely targeting point mutations in S. cerevisiae.
AB  - BACKGROUND: Precise targeted mutations are defined as targeted mutations that do
      not require the retention of other genetic changes, such as marker genes, near
      the mutation site. In the yeast, S. cerevisiae, there are several methods for
      introducing precise targeted mutations, all of which depend on inserting both a
      counter-selectable marker and DNA bearing the mutation. For example, the marker
      can first be inserted, and then replaced with either a long oligonucleotide
      carrying the mutation (delitto perfetto) or a PCR fragment synthesized with one
      primer containing the mutation (SSG mutagenesis). RESULTS: A hybrid method for
      targeting precise mutation into the genomes uses PCR fragments as in SSG
      mutagenesis together with a CORE cassette devised for delitto perfetto that
      contains the homing endonuclease SceI. This method, termed gsSSG mutagenesis, is
      much more efficient than standard SSG mutagenesis, allowing replacements to be
      identified without extensive screening of isolates. In gsSSG, recombination
      between the PCR fragment and the genome occurs equally efficiently regardless of
      the size of the fragment or the distance between the fragment end and the site of
      marker insertion. In contrast, the efficiency of incorporating targeted mutations
      by this method increases as the distance between the mutation and the marker
      insertion site decreases. CONCLUSION: gsSSG is an efficient way of introducing
      precise mutations into the genome of S. cerevisiae. The frequency of
      incorporating the targeted mutation remains efficient at least as far as 460 bp
      from the insertion site meaning that a single insertion can be used to create
      many different mutants. The overall efficiency of gsSSG can be estimated based on
      the distance between the mutation and the marker insertion, and this efficiency
      can be maximized by limiting the number of untargeted mutations. Thus, a single
      insertion of marker genes plus homing endonuclease cassette can be used to
      efficiently introduce precise point mutations through a region of > 900 bp.

PMID- 22141400
TI  - Preparation of Au-BiVO4 heterogeneous nanostructures as highly efficient visible
      light photocatalysts.
AB  - Au-BiVO(4) heterogeneous nanostructures have been successfully prepared through
      in situ growth of gold nanoparticles on BiVO(4) microtubes and nanosheets via a
      cysteine-linking strategy. The experimental results reveal that these Au-BiVO(4)
      heterogeneous nanostructures exhibit much higher visible-light photocatalytic
      activities than the individual BiVO(4) microtubes and nanosheets for both dye
      degradation and water oxidation. The enhanced photocatalytic efficiencies are
      attributed to the charge transfer from BiVO(4) to the attached gold nanoparticles
      as well as their surface plasmon resonance (SPR) absorption. These new
      heteronanostructures are expected to show considerable potential applications in
      solar-driven wastewater treatment and water splitting.

PMID- 22141401
TI  - Adherence to guidelines and effectiveness of inpatient treatment for unipolar
      depression.
AB  - OBJECTIVE: This naturalistic study is a contribution to randomized controlled
      trials which reflect only a very limited part of patients of the clinical
      practice and the relevance of guideline recommended treatment. METHODS: Adhering
      to quality assurance and development of treatment guidelines, 224 patients were
      evaluated for the effectiveness of inpatient treatment of unipolar depressive
      disorders by assessing admission and discharge depression scores, response and
      remission rates. Furthermore patients who were treated according to current
      guidelines (duration of treatment, dosage of antidepressants, combination of
      medication and psychotherapy) were compared to patients who did not meet those
      criteria. Primary outcome measure was the 17-item Hamilton Rating Scale for
      Depression (HAMD). Secondary outcome measures included Beck Depression Inventary
      (BDI). RESULTS: Mean HAMD-17 total score decreased from 28.9 to 8.0. Effect sizes
      d were similar to other naturalistic studies (d(HAMD) = 2.9; d(BDI) = 1.4); 84.4%
      of the patients could reach complete or partial response criteria for the HAMD
      17. Patients treated according to guidelines could reach remission in 73% of
      cases (HAMD) vs. 59.6% remission rate for non-guideline patients. CONCLUSION:
      This trial shows high remission rates in inpatient treatment of depression
      compared to similar effectiveness studies. Guideline according treatment might be
      superior to other treatment strategies.

PMID- 22141402
TI  - Economic analysis between entecavir and lamivudine for the treatment of chronic
      hepatitis B in Hong Kong.
AB  - BACKGROUND AND AIM: Tremendous healthcare resources have been spent on the
      management of chronic hepatitis B (CHB) and its related complications. Therefore,
      a proper evaluation of the cost-effectiveness of pharmacotherapy is vital in aid
      of decision-making. The aim of the present study was to examine the long-term
      economic and clinical influence if lamivudine was replaced by entecavir in a
      group of CHB patients. METHODS: A recently published decision analytic model was
      adapted to study the cost-effectiveness of 2 years of treatment of entecavir in a
      hypothetical cohort of 1000 hepatitis B e antigen (HBeAg)-negative CHB patients
      from a public hospital perspective. Compensated cirrhosis (CC) and de-compensated
      cirrhosis (DC) and hepatocellular carcinoma (HCC) events were projected to 10
      years. Hong Kong-specific health care costs were used. Quality Adjusted Life
      Years (QALYs) were calculated using the utility values obtained from a local
      study. RESULTS: In the base case analysis, compared with lamivudine, the use of
      entecavir was expected to reduce the incidences of CC, DC and HCC by 41.8%, 57.1%
      and 49.3%, respectively, and lead to a saving of $US 1.17 million in medical
      cost. The overall disease management cost for entecavir, which was 67.7% higher
      than lamivudine for 2 years treatment was reduced to 17.2% after projecting 2
      year treatment duration to 10 years. The incremental cost per QALY gained for
      entecavir compared with lamivudine was $US 13 759. CONCLUSIONS: Based on the
      recommended cost-effectiveness threshold of the World Health Organization,
      entecavir is considered cost-effective compared with lamivudine in treating CHB
      in Hong Kong when long term medical consequences were considered.

PMID- 22141403
TI  - Prednisolone therapy for atopic dermatitis is less effective in dogs with lower
      pretreatment serum 25-hydroxyvitamin D concentrations.
AB  - Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured in 20 dogs with
      atopic dermatitis prior to treatment with a standard therapeutic dosage of
      prednisolone (0.93-1.06 mg/kg) every other day for 5 weeks after 7 days of
      treatment with the same dosage once daily. The severity of their physical signs
      was scored before and 6 weeks after prednisolone treatment by the canine atopic
      dermatitis extent and severity index version 3 (CADESI-03) and the Edinburgh
      Pruritus Scale (EPS). The 20 dogs with atopic dermatitis that were treated with
      prednisolone did not have significantly lower serum concentrations of 25(OH)D
      than a group of 36 healthy dogs, and the physical severity of the atopic
      dermatitis was not correlated to pretreatment serum 25(OH)D concentrations.
      However, dogs which had a marked improvement of their physical signs, defined by
      a post-treatment EPS score of 0 and/or an 85% reduction in CADESI-03 score, had
      significantly higher pretreatment serum 25(OH)D concentrations than dogs with a
      suboptimal response (P = 0.003 and P = 0.03, respectively). Serum 25(OH)D
      concentrations were also measured in a previously published cohort of atopic dogs
      that were treated with ciclosporin. This cohort of dogs was recruited in a
      similar time frame to the prednisolone-treated dogs, and all samples were handled
      in the same way. In contrast to the prednisolone-treated dogs, there was no
      significant difference in 25(OH)D concentrations in dogs that responded optimally
      to ciclosporin compared with suboptimal responders. Additional studies are
      required to establish whether vitamin D has a synergistic therapeutic effect with
      prednisolone in dogs with atopic dermatitis.

PMID- 22141404
TI  - Muslim women's narratives about bodily change and care during critical illness: a
      qualitative study.
AB  - PURPOSE: To explore experiences of Jordanian Muslim women in relation to bodily
      change during critical illness. DESIGN: A longitudinal narrative approach was
      used. A purposive sample of 16 Jordanian women who had spent a minimum of 48 hr
      in intensive care participated in one to three interviews over a 6-month period.
      FINDINGS: Three main categories emerged from the analysis: the dependent body
      reflects changes in the women's bodily strength and performance, as they moved
      from being care providers into those in need of care; this was associated with
      experiences of a sense of paralysis, shame, and burden. The social body reflects
      the essential contribution that family help or nurses' support (as a proxy for
      family) made to women's adjustment to bodily change and their ability to make
      sense of their illness. The cultural body reflects the effect of cultural norms
      and Islamic beliefs on the women's interpretation of their experiences and
      relates to the women's understandings of bodily modesty. CONCLUSIONS: This study
      illustrates, by in-depth focus on Muslim women's narratives, the complex
      interrelationship between religious beliefs, cultural norms, and the experiences
      and meanings of bodily changes during critical illness. CLINICAL RELEVANCE: This
      article provides insights into vital aspects of Muslim women's needs and
      preferences for nursing care. It highlights the importance of including an
      assessment of culture and spiritual aspects when nursing critically ill patients.

PMID- 22141405
TI  - Unraveling the effect of genes and environment in the transmission of parental
      antisocial behavior to children's conduct disturbance, depression and
      hyperactivity.
AB  - BACKGROUND:   A critical issue in devising effective interventions for the
      treatment of children's behavioral and emotional problems identifying genuine
      family environmental factors that place children at risk. In most twin and family
      studies, environmental factors are confounded with both direct genetic risk from
      parents and the indirect effect of genes influencing parents' ability to provide
      an optimal rearing environment. The present study was undertaken to determine
      whether parental psychopathology, specifically parental antisocial behavior
      (ASP), is a genuine environmental risk factor for juvenile conduct disturbance,
      depression and hyperactivity, or whether the association between parental ASP and
      children's behavioral and emotional problems can be explained as a secondary
      consequence of the intergenerational transmission of genetic factors. METHODS:  
      An extended children of twins design comprised of data collected on 2,674 adult
      female and male twins, their spouses, and 2,454 of their children was used to
      test whether genetic and/or family environmental factors best accounted for the
      association between parental antisocial behavior and children's behavioral
      problems. An age-matched sample of 2,826 juvenile twin pairs from the Virginia
      Twin Study of Adolescent Behavioral Development was also included to examine
      developmental differences in gene expression by partitioning child-specific
      transmissible effects from those effects that persist into adulthood. The fit of
      alternative models was evaluated using the statistical program Mx. RESULTS:   We
      found distinct patterns of transmission between parental antisocial behavior and
      juvenile conduct, depression and hyperactivity. Genetic and family environmental
      factors accounted for the resemblance between parents' ASP and children's conduct
      disturbance. Family environmental factors alone explained the association between
      child depression and parental ASP, and the impact of parental ASP on
      hyperactivity was entirely genetic. CONCLUSIONS:   These findings underscore
      differences in the contribution of genetic and environmental factors on the
      patterns of association between parental antisocial behavior and juvenile
      psychopathology, having important clinical implications for the prevention and
      amelioration of child behavioral and emotional problems.

PMID- 22141406
TI  - In vitro antiplasmodial activity and cytotoxicity of extracts and fractions of
      Vitex madiensis, medicinal plant of Gabon.
AB  - Vitex madiensis Oliv. (Lamiaceae) is traditionally used to treat malaria symptoms
      in Haut-Ogooue, Gabon. Leaves and stem barks extracts were obtained using
      dichloromethane (CH(2)Cl(2)), ethyl acetate (EtOAc) and methanol (MeOH) as
      extraction solvents and fractionated on silica gel column. The in vitro
      antiplasmodial activity of CH(2)Cl(2), EtOAc and MeOH extracts and fractions was
      evaluated against the chloroquine-resistant FCB strain and field isolates of
      Plasmodium falciparum using the DELI test. The cytotoxicity of the extracts was
      tested on MRC-5 and THP1 cells using the tetrazolium salt MTT colorimetric assay,
      and the selectivity index (SI) of each extract was calculated. CH(2)Cl(2)
      extract, the EA1 fraction from EtOAc extract of stem barks and cyclohexane
      (L(cycl)), dichloromethane (L(DM)) and butanol (L(but)) fractions from MeOH/H(2)O
      extract of leaves exhibited the highest in vitro antiplasmodial activity on FCB
      strain and field isolates (IC(50) from 0.53 to 4.87 MUg/ml) with high selectivity
      index (of 20.15-1800). These data support the use of V. madiensis in malaria
      treatment along with continued investigations within traditional medicines in the
      search of new antimalarial agents. The EA1, C(6)H(12) and CH(2)Cl(2) fractions
      could be selected for future investigation or/and for the treatment of malaria
      symptoms after standardization.

PMID- 22141407
TI  - Management of asthma by pregnant women attending an Australian maternity
      hospital.
AB  - AIMS: The safety of preventive asthma medicines during pregnancy has already been
      established. The aim of this study was to assess asthma management by women
      during pregnancy. METHODS: Pregnant women attending the out-patient clinics of an
      Australian maternity hospital completed a questionnaire about their asthma
      medication use and symptoms. Parameters associated with changes in asthma
      medicine use are presented as odds ratio with a 95% confidence level. P-values
      <0.05 indicated statistical significance. RESULTS: Participants (n = 102) self
      reported worsening of their asthma symptoms during pregnancy compared with the
      pre-pregnancy period, both during the day (P = 0.003) and night (P = 0.044). The
      number of participants whose asthma was treated by a medical professional
      decreased from 81 (79.4%) before pregnancy to 67 (65.7%) during pregnancy (P =
      0.008). The use of regular asthma medicines (preventers and symptom controllers
      alone or in combination) decreased during pregnancy (P < 0.001 and P = 0.012,
      respectively), while the use of intermittent therapies (relievers) increased (P =
      0.004) during pregnancy. Being treated by a medical professional during pregnancy
      (P = 0.033), a history of asthma medicine use before pregnancy (P = 0.015) and
      younger age of first asthma diagnosis (P = 0.046) were associated with the use of
      asthma medicines during pregnancy. CONCLUSIONS: Despite worsening of asthma
      symptoms, many pregnant women do not take regular preventive asthma medicines.
      Ongoing assessment of asthma control during pregnancy, medication review and
      adjustments in therapy by health professionals might facilitate asthma
      management.

PMID- 22141408
TI  - Effects of acute inflammation induced in the rat paw on the deep digital flexor
      tendon.
AB  - The tendon is commonly affected by inflammation, and in such situations, the
      tissue undergoes a process of reorganization of the extracellular matrix to
      improve and regenerate the affected region. Little is known about the mechanisms
      that trigger inflammation in the tissues surrounding the affected area. The
      objective of this study was to biochemically and morphologically analyze the deep
      digital flexor tendon at the peak of acute inflammation in the rat paw. Wistar
      rats were divided into the following three groups: those that received injection
      of 1% carrageenan, those that received 0.9% NaCl, and those that received
      nothing. The deep digital flexor tendon was divided into the distal, proximal,
      and intermediate regions. For biochemical analysis, the tendons were treated with
      guanidine hydrochloride and analyzed by sodium dodecyl sulfate-polyacrilamide gel
      electrophoresis. Proteins, glycosaminoglycans (GAGs), and hydroxyproline were
      quantified, and metalloproteinases were analyzed. The GAGs were analyzed by
      agarose gel electrophoresis. Tissue sections were stained with hematoxylin-eosin,
      toluidine blue, and Ponceau SS. The content of proteins and GAGs was smaller in
      the group receiving the application of carrageenan. The concentration of
      hydroxyproline in the two tendon regions that respond to tension forces was
      higher in the inflammation group. The metalloproteinase-9 was detected in the
      distal region, and a thicker epitenon with cellular infiltrate was observed in
      the groups with inflamed paws. Meanwhile, a better organization of collagen
      bundles was observed in the two tension regions of that same group. Our results
      show that although the tendon was not directly inflamed, changes in the
      surrounding structural and biochemical parameters were observed.

PMID- 22141409
TI  - Standardized comparison of prostate morcellators using a new ex-vivo model.
AB  - BACKGROUND AND PURPOSE: Transurethral laser enucleation of the prostate is a
      common therapeutic option for the treatment of benign prostate enlargement.
      Evacuation of the enucleated tissue from the bladder is usually performed by
      electric morcellators. Until now, a standardized evaluation of the different
      morcellator settings does not exist. Therefore, we developed an ex-vivo model to
      find the best settings for four different morcellators. MATERIALS AND METHODS: We
      morcellated pieces of a prostate adenoma after an open adenomectomy. The same
      speed settings were used to morcellate commercially available minced meat, fine
      pork sausage meat, and bovine heart, all of which had been cooked for 10 minutes
      using a Piranha Morcellator. We also morcellated raw pig perirenal fat tissue,
      raw pig liver, and raw bovine heart. The pieces were morcellated at different
      speed settings in an open water tank filled with saline. Because raw bovine heart
      showed to be the most equivalent tissue, we morcellated five pieces with four
      different settings of four different morcellators: The Piranha, the VersaCut, and
      two morcellator prototypes. RESULTS: The median retrieval rate for the prostate
      adenoma was 14.02 (3.7-19.8) g/min. The retrieval rate for raw bovine heart was
      13.75 (5.66-20) g/min. The maximum morcellation rates of the morcellators were:
      Piranha 20 (19.3-21.4) g/min, VersaCut 10.8 (8.2-13.1) g/min, Karl Storz
      prototype 9.8 (7.9-10.76) g/min, and Richard Wolf prototype 38.6 (35.3-42.9)
      g/min. CONCLUSION: Raw bovine heart tissue is suitable for ex-vivo testing of
      prostate morcellators and can replace human prostate tissue in this standardized
      setting. In our ex-vivo study, the morcellation rates of the different
      morcellators increased with optimized oscillation speed and suction power
      settings. This needs to be confirmed in clinical studies.

PMID- 22141410
TI  - Gianotti-Crosti syndrome following childhood vaccinations.
AB  - A 19-month-old boy was evaluated for a skin eruption after recent vaccinations.
      Clinical and histopathologic findings supported a diagnosis of Gianotti-Crosti
      syndrome (GCS). This case report examines the link between GCS and vaccinations,
      particularly the diphtheria, tetanus, and pertussis vaccine and the varicella
      virus live vaccine.

PMID- 22141411
TI  - Extracellular recombinant annexin II confers UVC-radiation resistance and
      increases the Bcl-xL to Bax protein ratios in human UVC-radiation-sensitive
      cells.
AB  - In this study, we found that refractoriness to ultraviolet (UVC) light-induced
      cell death was increased in UVC-radiation-sensitive cells derived from Cockayne
      syndrome patients when the cells were precultured in medium supplemented with
      recombinant annexin II (rANX II). In CS3BES cells, an immortal cell line derived
      from Cockayne syndrome patients, the rANX II supplementation-induced UVC
      radiation resistance was suppressed by treatment with an anti-annexin II antibody
      and EGTA. The amount of biotinylated annexin II on the cell surface increased in
      the rANX II-supplemented cells but did not increase in the cells that were
      cotreated with rANX II and EGTA. The capacity to remove UVC-radiation-damaged
      DNA, (6-4) photoproducts and cyclobutane pyrimidine dimers, was the same in cells
      that were precultured with rANX II and in control cells that did not receive rANX
      II supplementation. The rANX II supplementation-induced UVC-radiation resistance
      was also observed in nucleotide excision repair-deficient cells and xeroderma
      pigmentosum group A-downregulated cells. The Bcl-xL to Bax protein ratios, an
      index of survival activity in cells exposed to lethal stresses, were increased in
      the cells that had been precultured in rANX II for 24 h prior to UVC irradiation.
      Treatment with a phosphatidylinositol 3-kinase inhibitor suppressed the increased
      UVC-radiation resistance and Bcl-xL to Bax ratios in the cells with rANX II
      supplementation. Furthermore, downregulation of Bcl-xL by siRNA transfection also
      suppressed the UVC-radiation resistance that was induced by rANX II
      supplementation. These results suggest that the increase in the Bcl-xL to Bax
      ratios may be associated with enhanced resistance to UVC-radiation-induced cell
      death.

PMID- 22141413
TI  - Factors influencing Dutch practice nurses' intention to adopt a new smoking
      cessation intervention.
AB  - AIMS: This article is a report of a study that aimed to identify factors
      influencing practice nurses' and nurse practitioners' intention to adopt a new
      smoking cessation intervention. BACKGROUND: Although effective smoking cessation
      interventions exist and practice nurses can offer a considerable resource in
      advertising patients to quit smoking, due to several reasons the majority of
      practice nurses do not implement these interventions. METHODS: A cross-sectional
      study was undertaken among Dutch practice nurses and nurse practitioners working
      in general practices (n = 139) using electronic questionnaires. Data were
      collected from January until March in 2009. T-tests were used to compare adopters
      with non-adopters about their predisposing and motivational factors. Logistic
      regression analyses were conducted to assess the variation in intention explained
      by these factors. RESULTS: The majority of practice nurses did not intend to
      adopt the new intervention (n = 85; 61.2%). More practice nurses than nurse
      practitioners intended to adopt the intervention. Attitude and perceived social
      norms were found to be positively correlated with the intention to adopt the
      intervention whereas satisfaction with current smoking cessation activities was
      found to be negatively correlated. CONCLUSION: Important associations were found
      between profession, attitude, social norms and satisfaction, and the intention to
      adopt the new smoking cessation intervention. Practice nurses who do not intend
      to adopt need to be persuaded of the advantages of adopting. Perceived social
      norms need to be restructured and before presenting the intervention to a general
      practice current smoking cessation activities should be determined to increase
      the intervention's compatibility with these current practices.

PMID- 22141414
TI  - Complete rRNA sequence, arrangement of tandem repeated units and phylogeny of
      Nosema fumiferanae from spruce budworm, Choristoneura fumiferana (Clemens).
AB  - We provide molecular systematics of a microporidian species, Nosema fumiferanae,
      one of the most common natural enemies of spruce budworm, Choristoneura
      fumiferana. The uncharacterized flanking region upstream of the large subunit
      (LSU) rRNA and the complete rRNA cistron of N. fumiferanae was 4,769 bp long. The
      organization of the rRNA gene was 5'-LSU rRNA-ITS-SSU rRNA-IGS-5S-3' and
      corresponded primarily to most insect (i.e. lepidopteran) Nosema species
      identified and classified to date. Phylogenetic analysis based on the complete
      rRNA cistron indicated that N. fumiferanae is closely related to Nosema plutellae
      and is correctly assigned to the "true" Nosema group. Suggestions were provided
      on a criterion to delineate the "true" Nosema from other microsporidian species.

PMID- 22141415
TI  - Psychotherapist self-disclosure: ethical and clinical considerations.
AB  - Self-disclosure is an ever present and unavoidable aspect of psychotherapy. But,
      why, how, and when it is done requires careful forethought. The use of self
      disclosure is discussed in the context of boundaries, highlighting its ethical
      and appropriate use in psychotherapy. Rather than avoiding self-disclosure out of
      a fear of violating ethical and professional standards, a thoughtful approach to
      addressing self-disclosure is presented. Recommendations for the ethical and
      effective use of self-disclosure are provided to include the use of ethical
      decision-making models and thoughtful consideration of contextual factors that
      include the psychotherapist's motivations, the client's treatment needs and
      personal history, the psychotherapist's theoretical orientation, and individual
      differences to include each aspect of the client's and psychotherapist's
      diversity. Recommendations for psychotherapists considering the use of self
      disclosure with clients are made along with specific recommendations for the
      profession of psychology to provide greater guidance on the ethical, effective,
      and clinically appropriate use of self-disclosure.

PMID- 22141416
TI  - Directions for research on self-disclosure and immediacy: moderation, mediation,
      and the inverted U.
AB  - The psychotherapist's use of self-disclosure (SD) and immediacy has been a
      controversial topic over the decades. In this article, some ingredients are
      described that will help advance knowledge in the area of the therapist SD and
      immediacy. More than has been the case, researchers in this area should construct
      clear definitions of the SD/immediacy variables being investigated, and make sure
      that their operationalizations are consistent with these definitions. In
      addition, it is argued that if the field is to advance, at this point in time
      researchers need to examine "who, what, when, and where" questions, making use of
      in-principle moderation, that is, the study of which SD/immediacy responses are
      most effective with what patients, suffering from what problems and disorders,
      when offered by which therapists doing what kinds of psychotherapy? In addition,
      the study of mediation is suggested, as is researchers' taking into account the
      operation of the inverted U when studying the frequency, intensity, or duration
      of SD/immediacy.

PMID- 22141417
TI  - Reflections on the meaning of clinician self-reference: are we speaking the same
      language?
AB  - Self-reference refers to clinician revelations about themselves. Theory and
      research on self-reference are limited by a lack of uniform conceptualizations.
      This paper discusses two types of self-reference, self-disclosure, and self
      involving responses. Included are definitions of each type of self-reference;
      description of definitional inconsistencies in the literature; discussion of
      prevalence, functions, and the multidimensional nature of self-reference; and
      practice implications and research recommendations. The ideas presented herein
      are intended to prompt researchers, practitioners, and educators to carefully
      consider the nature, scope, and functions of self-reference, and in doing so,
      bring greater conceptual and operational clarity to their work.

PMID- 22141419
TI  - Exploration of session process: relationship to depth and alliance.
AB  - This study investigates the relationship between the Depth of elaboration, the
      therapeutic alliance, and dimensions of the psychotherapy process--the therapist
      interventions, the patient contributions, and patient/therapist patterns of
      interaction. Sixty psychotherapy sessions that were audio-taped and transcribed
      were rated by external judges by using a battery of instruments that included the
      Psychotherapy Process Q-Set (Jones, 1985, 2000), the Working Alliance Inventory
      Observer (Horvath, 1981, 1982; Horvath & Greenberg, 1989), and the Depth Scale of
      Session Evaluation Questionnaire (Stiles & Snow, 1984a). The results show a
      significant positive correlation between Depth and therapeutic alliance, as well
      as between Depth, therapeutic alliance, and some variables of the therapeutic
      process. The findings indicate the importance of therapist interventions that
      focus on the patient's affects, relational patterns, and the "here and now" of
      the relationship in the increase of the Depth of elaboration and therapeutic
      alliance. The clinical implications of this study will be discussed.

PMID- 22141420
TI  - Alliance-focused therapy for anorexia nervosa: integrative relational and
      behavioral change treatments in a single-case experimental design.
AB  - Evidence supporting outpatient treatments for anorexia nervosa (AN) is severely
      lacking, due to low retention and poor outcome. One explanation for drop-out is
      weak treatment alliances. A single-case experimental analysis accompanied by in
      depth qualitative description is presented for Ms. O, who received a novel
      treatment for AN called Alliance Focused Treatment (AFT) that attends to ruptures
      in the alliance, interpersonal difficulties and emotional avoidance. At intake
      Ms. O met diagnostic criteria for AN, Major Depressive Disorder, and Social
      Phobia. She was characterized as having symptoms of Obsessive Compulsive,
      Avoidant, and Depressive personality disorders. Treatment began with a Baseline
      followed by the experimental (AFT) and comparison treatments (Behavioral Change
      Treatment [BCT]) using a replicated experimental single-case phase change design.
      Graphs of slopes of kilocalorie and alliance change facilitated observation of
      treatment effects. Ms. O participated in 16 sessions of AFT and 8 sessions of BCT
      with specific benefits. Ratings of the treatment alliance were consistently high
      and she evidenced significant changes in weight, quality of life, and personality
      pathology. Associations between rupture/repair episodes and kilocalorie increases
      were observed. The utility of the treatment relationship in facilitating
      emotional expression was evident. At posttreatment, Ms. O endorsed cognitive AN
      symptoms, although these were not explicitly treated. This study provides
      preliminary support for the feasibility and effect of AFT and BCT, and highlights
      the importance of the alliance in treating adults with AN. Further research on
      emotion regulation in AN and its effect on the treatment relationship are needed.

PMID- 22141421
TI  - Early growth response-1 contributes to steatosis development after acute ethanol
      administration.
AB  - BACKGROUND: Previous work demonstrated that the transcription factor, early
      growth response-1 (Egr-1), participates in the development of steatosis (fatty
      liver) after chronic ethanol (EtOH) administration. Here, we determined the
      extent to which Egr-1 is involved in fatty liver development in mice subjected to
      acute EtOH administration. METHODS: In acute studies, we treated both wild-type
      and Egr-1 null mice with either EtOH or phosphate-buffered saline (PBS) by
      gastric intubation. At various times after treatment, we harvested sera and
      livers and quantified endotoxin, indices of liver injury, steatosis, and hepatic
      Egr-1 content. In chronic studies, groups of mice were fed liquid diets
      containing either EtOH or isocaloric maltose-dextrin for 7 to 8 weeks. RESULTS:
      Compared with controls, acute EtOH-treated mice showed a rapid, transient
      elevation in serum endotoxin beginning 30 minutes after treatment. One hour
      postgavage, livers from EtOH-treated mice exhibited a robust elevation of both
      Egr-1 mRNA and protein. By 3 hours postgavage, liver triglyceride increased in
      EtOH-treated mice as did lipid peroxidation. Acute EtOH treatment of Egr-1-null
      mice showed no Egr-1 expression, but these animals still developed elevated
      triglycerides, although significantly lower than EtOH-fed wild-type littermates.
      Despite showing decreased fatty liver, EtOH-treated Egr-1 null mice exhibited
      greater liver injury. After chronic EtOH feeding, steatosis and liver enlargement
      were clearly evident, but there was no indication of elevated endotoxin. Egr-1
      levels in EtOH-fed mice were equal to those of pair-fed controls. CONCLUSIONS:
      Acute EtOH administration induced the synthesis of Egr-1 in mouse liver. However,
      despite its robust increase, the transcription factor had a smaller, albeit
      significant, function in steatosis development after acute EtOH treatment. We
      propose that the rise in Egr-1 after acute EtOH is an hepatoprotective adaptation
      to acute liver injury from binge drinking that is triggered by EtOH metabolism
      and elevated levels of endotoxin.

PMID- 22141423
TI  - Do the effects of a family intervention on alcohol and drug use vary by nativity
      status?
AB  - To examine whether the intervention effects of Familias Unidas, compared to
      community practice, on Hispanic adolescent alcohol and drug use varies by
      nativity status (i.e., U.S.-born and foreign-born). A total of 213 eighth grade
      Hispanic adolescents with behavior problems and their primary caregivers were
      assigned randomly to one of two conditions: Familias Unidas or Community Control.
      Participants were assessed at baseline and at 6, 18, and 30 months post baseline.
      Results showed that, the effects of Familias Unidas on alcohol use was moderated
      by nativity status. Specifically, Familias Unidas was efficacious in
      preventing/reducing alcohol use for U.S.-born youth, but not foreign-born. No
      moderating effects were found for drug use. These findings suggest that
      prevention interventions may be more efficacious in preventing/reducing alcohol
      use among certain Hispanic adolescent subgroups.

PMID- 22141422
TI  - Modeling formalisms in Systems Biology.
AB  - Systems Biology has taken advantage of computational tools and high-throughput
      experimental data to model several biological processes. These include signaling,
      gene regulatory, and metabolic networks. However, most of these models are
      specific to each kind of network. Their interconnection demands a whole-cell
      modeling framework for a complete understanding of cellular systems. We describe
      the features required by an integrated framework for modeling, analyzing and
      simulating biological processes, and review several modeling formalisms that have
      been used in Systems Biology including Boolean networks, Bayesian networks, Petri
      nets, process algebras, constraint-based models, differential equations, rule
      based models, interacting state machines, cellular automata, and agent-based
      models. We compare the features provided by different formalisms, and discuss
      recent approaches in the integration of these formalisms, as well as possible
      directions for the future.

PMID- 22141425
TI  - Factors associated with non-adherence to highly active antiretroviral therapy in
      Nairobi, Kenya.
AB  - BACKGROUND: Antiretroviral therapy (ART) requires high-level (> 95%) adherence.
      Kenya is rolling out ART access programmes and, issue of adherence to therapy is
      therefore imperative. However, published data on adherence to ART in Kenya is
      limited. This study assessed adherence to ART and identified factors responsible
      for non adherence in Nairobi. METHODS: This is a multiple facility-based cross
      sectional study, where 416 patients aged over 18 years were systematically
      selected and interviewed using a structured questionnaire about their experience
      taking ART. Additional data was extracted from hospital records. Patients were
      grouped into adherent and non-adherent based on a composite score derived from a
      three questions adherence tool developed by Center for Adherence Support
      Evaluation (CASE). Multivariate regression model was used to determine predictors
      of non-adherence. RESULTS: Overall, 403 patients responded; 35% males and 65%
      females, 18% were non-adherent, and main (38%) reason for missing therapy were
      being busy and forgetting. Accessing ART in a clinic within walking distance from
      home (OR = 2.387, CI.95 = 1.155-4.931; p = 0.019) and difficulty with dosing
      schedule (OR = 2.310, CI.95 = 1.211-4.408, p = 0.011) predicted non-adherence.
      CONCLUSIONS: The study found better adherence to HAART in Nairobi compared to
      previous studies in Kenya. However, this can be improved further by employing
      fitting strategies to improve patients' ability to fit therapy in own lifestyle
      and cue-dose training to impact forgetfulness. Further work to determine why
      patients accessing therapy from ARV clinics within walking distance from their
      residence did not adhere is recommended.

PMID- 22141424
TI  - MALDI mass spectrometric imaging of cardiac tissue following myocardial
      infarction in a rat coronary artery ligation model.
AB  - Although acute myocardial infarction (MI) is consistently among the top causes of
      death in the United States, the spatial distribution of lipids and metabolites
      following MI remains to be elucidated. This work presents the investigation of an
      in vivo rat model of MI using mass spectrometric imaging (MSI) and multivariate
      data analysis. MSI was conducted on cardiac tissue following a 24-h left anterior
      descending coronary artery ligation to analyze multiple compound classes. First,
      the spatial distribution of a small metabolite, creatine, was used to identify
      areas of infarcted myocardium. Second, multivariate data analysis and tandem mass
      spectrometry were used to identify phospholipid (PL) markers of MI. A number of
      lysophospholipids demonstrated increased ion signal in areas of infarction. In
      contrast, select intact PLs demonstrated decreased ion signal in the area of
      infarction. The complementary nature of these two lipid classes suggests
      increased activity of phospholipase A(2), an enzyme that has been implicated in
      coronary heart disease and inflammation.

PMID- 22141426
TI  - Effect of sibutramine on 5-hydroxyindole acetic acid levels and selected
      oxidative biomarkers on brain regions of female rats in the presence of zinc.
AB  - A number of drugs, like sibutramine, which are used clinically in weight control,
      act on serotonergic metabolism. However, their relation with zinc and free
      radical (FR) production in central nervous system remains unknown. This study
      aimed to evaluate the effect of sibutramine and zinc on FR production. Female
      Wistar rats (about 250 g) were used in this study. The animals received 400
      MUg/kg of zinc and 10 mg/kg of sibutramine intraperitoneally every 36 hr for 15
      days. At the end of the study, the rats were killed and their brains used for the
      measurement of lipid peroxidation thiobarbituric acid-reactive substances
      (TBARS), reduced glutathione (GSH), hydrogen peroxide (H(2) O(2) ), calcium and 5
      hydroxyindole acetic acid (5-HIAA) levels, all by means of validated methods.
      Corporal weight and food consumption were found to be decreased in the
      zinc/sibutramine group. TBARS decreased in cortex, hemispheres and medulla
      oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine
      group. Zinc given alone and in combination with sibutramine decreased H(2) O(2) 
      concentration in cortex, hemispheres and cerebellum but increased calcium and 5
      HIAA concentration in all brain regions. Our results suggest that sibutramine and
      zinc are associated with weight loss, an effect that was more pronounced in the
      group treated with both drugs. Reduction in oxidative stress may be involved in
      these effects.

PMID- 22141427
TI  - The role of deliberate practice in the acquisition of clinical skills.
AB  - BACKGROUND: The role of deliberate practice in medical students' development from
      novice to expert was examined for preclinical skill training. METHODS: Students
      in years 1-3 completed 34 Likert type items, adapted from a questionnaire about
      the use of deliberate practice in cognitive learning. Exploratory factor analysis
      and reliability analysis were used to validate the questionnaire. Analysis of
      variance examined differences between years and regression analysis the
      relationship between deliberate practice and skill test results. RESULTS: 875
      students participated (90%). Factor analysis yielded four factors: planning,
      concentration/dedication, repetition/revision, study style/self reflection.
      Student scores on 'Planning' increased over time, score on sub-scale
      'repetition/revision' decreased. Student results on the clinical skill test
      correlated positively with scores on subscales 'planning' and
      'concentration/dedication' in years 1 and 3, and with scores on subscale
      'repetition/revision' in year 1. CONCLUSIONS: The positive effects on test
      results suggest that the role of deliberate practice in medical education merits
      further study. The cross-sectional design is a limitation, the large
      representative sample a strength of the study. The vanishing effect of
      repetition/revision may be attributable to inadequate feedback. Deliberate
      practice advocates sustained practice to address weaknesses, identified by (self
      )assessment and stimulated by feedback. Further studies should use a longitudinal
      prospective design and extend the scope to expertise development during residency
      and beyond.

PMID- 22141428
TI  - High ferromagnetic transition temperature in PbS and PbS:Mn nanowires.
AB  - Spontaneous magnetization measured in the temperature range 5-300 K with high
      ferromagnetic transition temperature (T(c)) has been observed in both undoped and
      Mn doped (2-8 mol %) PbS nanowires (diameter 30 nm) in polymer. For undoped
      sample, we find T(c) ~ 290 K while for doped samples T(c) varies between 310-340
      K depending on Mn concentrations. Both T(c) and coercive fields are critically
      dependent on Mn concentrations. Coercive fields show a T(0.5) dependence with
      temperature for a moderate concentration of Mn (4 mol %) in PbS while it deviates
      from T(0.5) behavior for higher Mn concentrations. Anionic defects arising out of
      nonstoichiometric growth is solely responsible for the observed magnetism in
      undoped PbS nanowires. The role of intrinsic strain along with reduced
      dimensionality in determining such high T(c) and overall magnetizations has been
      discussed.

PMID- 22141429
TI  - More on: racial differences in venous thromboembolism.

PMID- 22141430
TI  - an Obituary for GFR as the main marker for kidney function?
AB  - This publication comments on the recently published findings of a study by Eloot
      et al. (cJASN, 6: 1266-1273, 2011) that evaluated the correlation between several
      formulae for calculating estimated GFR (eGFR) and different low molecular weight
      uremic toxins; eGFRs were based on serum creatinine (SCrea), cystatin C (Cys C),
      or a combination of both. Unexpectedly, the correlations for the different
      solutes were highly inconsistent, irrespective of the eGFR formula. On the other
      hand, the different eGFR formulae gave consistent results per solute. Correlation
      coefficients for some solutes were low (hippuric acid, p-cresylsulfate, indole
      acetic acid, uric acid, asymmetric dimethylarginine) to nonsignificant (carboxy
      methyl-propyl-furanpropionic acid). These data point to the fact that eGFR is a
      deceiving predictor of uremic solute concentration and their biological action;
      this inconsistency is very likely the result of the impact of other factors
      affecting concentration, such as tubular secretion, generation by intestinal
      flora and metabolism.

PMID- 22141431
TI  - Multiple eccrine poromas in the paw of a dog.
AB  - A 5-year-old, spayed female boxer dog presented to the referring veterinarian
      with a year-long history of swelling, ulceration and pain in the pawpad of the
      fourth digit of the right forelimb. Histologically, the pawpad was expanded by a
      mass composed of small polygonal cells forming broad bands and trabeculae within
      the lower epidermis that often infiltrated and replaced the overlying
      keratinocytes and that extended into the dermis. Lobules of eccrine glands within
      the deep dermis occasionally had one or more eccrine ducts that were lined by
      neoplastic ductal epithelial cells that formed papillary projections lined by one
      to two layers of neoplastic cells. Approximately 1 month after amputation of the
      fourth digit pad, several smaller nodular masses developed in multiple digital
      pads and the metacarpal pad of the same paw. All of the neoplasms were
      histologically identical to eccrine poroma (juxtaepidermal acrospiroma), a common
      benign neoplasm in humans that originates from the acrosyringium and upper dermal
      duct of eccrine glands. To the authors' knowledge this is the first report
      documenting an eccrine poroma in a dog.

PMID- 22141432
TI  - The impact of an outpatient palliative care consultation on symptom burden in
      advanced prostate cancer patients.
AB  - OBJECTIVES: There are limited studies characterizing cancer-related symptoms in
      outpatient advanced prostate cancer patients. The aim of this retrospective study
      was to describe the impact of an outpatient palliative care (PC) consultation on
      symptoms in patients with advanced prostate cancer. METHODS: We retrospectively
      reviewed the medical records of 55 consecutive patients with advanced prostate
      cancer seen in our institution's outpatient PC center. Information regarding
      demographics, disease status, Edmonton Symptom Assessment System (ESAS) scores,
      Eastern Cooperative Oncology Group (ECOG) Performance Status, laboratory data,
      and pharmacological interventions were analyzed. RESULTS: The median age of the
      study's patients was 66 years old, with 73% Caucasian ethnicity. All patients had
      metastatic disease and 96% had received prior cytotoxic chemotherapy. The most
      frequently occurring symptoms upon presentation were pain, fatigue, and
      drowsiness (>50%). Pain and fatigue were also the most severe symptoms, each
      having median ESAS scores of 7 (on a 0-10 scale). We instituted a median of 3
      pharmacological interventions per patient, with a median of 15 days to follow-up
      assessment. At follow-up, patients reported significant symptom improvements in
      pain, drowsiness, fatigue, depression, sleep, sense of well-being, and anxiety.
      CONCLUSIONS: Based on our preliminary data, we conclude that patients with
      advanced prostate cancer referred to PC experience severe and clinically
      significant symptoms. An outpatient PCconsultation is associated with significant
      symptom improvement in this subset of a distressed population. Future prospective
      studies are warranted to further describe symptom burden and the role for
      outpatient PC for advanced prostate cancer patients.

PMID- 22141433
TI  - Increasing access to the MDR-TB surveillance programme through a collaborative
      model in western Kenya.
AB  - OBJECTIVE: Kenya, like many resource-constrained countries, has a single
      mycobacterial laboratory, centrally located in Nairobi, with capacity for drug
      susceptibility testing (DST) - the gold standard in diagnosing drug-resistant
      tuberculosis. We describe and evaluate a novel operational design that attempts
      to overcome diagnostic delivery barriers. METHODS: Review of the public DST
      programme identified several barriers limiting access: lack of programme
      awareness amongst physicians, limited supplies, unreliable transport and no
      specimen tracking methods. Staff visited 19 clinic sites in western Kenya and
      trained healthcare providers in regard to the novel diagnostics model. Provincial
      laboratory registries were reviewed to assess utilization of DST services prior
      to and after programme modification. RESULTS: Onsite training consisted of the
      inclusion criteria for re-treatment patients - the high-priority group for DST.
      Additionally, infrastructural support established a stable supply chain. An
      existing transport system was adapted to deliver sputum specimens. Task shifting
      created an accession and tracking system of specimens. During the 24 months post
      implementation, the number of re-treatment specimens from the catchment area
      increased from 9.1 to 23.5 specimens per month. In comparing annual data pre- and
      post-implementation, the proportion of re-treatment cases receiving DST increased
      from 24.7% (n = 403) to 32.5% (n = 574) (P < 0.001), and the number of multidrug
      resistant (MDR) TB cases increased from 5 to 10 cases. CONCLUSION: The delivery
      model significantly increased the proportion of re-treatment cases receiving DST.
      Barriers to accessing the national MDR-TB surveillance programme can be overcome
      through an operational model based on pragmatic use of existing services from
      multiple partners.

PMID- 22141435
TI  - Immunohistochemical analysis of the effects of estrogen on intraarticular
      neurogenic inflammation in a rat anterior cruciate ligament transection model of
      osteoarthritis.
AB  - Synovitis is considered as one of the factors associated with the pathogenesis of
      osteoarthritis (OA). There is currently a significant amount of research linking
      estrogen deficiencies with the development of OA in estrogen-deficient women,
      including postmenopausal women; however, the exact etiology remains unclear.
      Various neuropeptides, such as substance P (SP) and calcitonin gene-related
      peptide (CGRP), have been shown to contribute to synovitis in OA joints, and the
      influence of estrogen on the expressions of SP and CGRP in the synovium of OA
      joints has been noted. After ovariectomy (OVX) followed by estradiol (E2)
      replacement, 24 female rats were divided into three groups: OVX group, OVX + E2
      replacement group (E2 group), and a sham group. All rats underwent transection of
      the anterior cruciate ligament at the same time. After 30 days, the histological
      findings of knee joints by hematoxylin-eosin staining and immunofluorescence
      staining of protein gene product 9.5 (pan-neuronal marker), SP, and CGRP were
      compared among experimental groups. The degree of synovitis in the OVX group was
      higher than in the E2 and sham groups. No significant differences in the density
      of protein gene product 9.5-immunoreactive nerve fibers were observed among the
      three experimental groups, but the density of SP- or CGRP-immunoreactive nerve
      fibers in the OVX group was significantly higher than in the E2 and sham groups.
      These findings suggest that estrogen partly regulates intraarticular neurogenic
      inflammation in OA joints by modulating the expressions of neuropeptides in the
      synovium.

PMID- 22141434
TI  - Annual research review: the nature and classification of reading disorders--a
      commentary on proposals for DSM-5.
AB  - This article reviews our understanding of reading disorders in children and
      relates it to current proposals for their classification in DSM-5. There are two
      different, commonly occurring, forms of reading disorder in children which arise
      from different underlying language difficulties. Dyslexia (as defined in DSM-5),
      or decoding difficulty, refers to children who have difficulty in mastering the
      relationships between the spelling patterns of words and their pronunciations.
      These children typically read aloud inaccurately and slowly, and experience
      additional problems with spelling. Dyslexia appears to arise principally from a
      weakness in phonological (speech sound) skills, and there is good evidence that
      it can be ameliorated by systematic phonic teaching combined with phonological
      awareness training. The other major form of reading difficulty is reading
      comprehension impairment. These children read aloud accurately and fluently, but
      have difficulty understanding what they have read. Reading comprehension
      impairment appears to arise from weaknesses in a range of oral language skills
      including poor vocabulary knowledge, weak grammatical skills and difficulties in
      oral language comprehension. We suggest that the omission of reading
      comprehension impairment from DSM-5 is a serious one that should be remedied.
      Both dyslexia and reading comprehension impairment are dimensional in nature, and
      show strong continuities with other disorders of language. We argue that
      recognizing the continuities between reading and language disorders has important
      implications for assessment and treatment, and we note that the high rates of
      comorbidity between reading disorders and other seemingly disparate disorders
      (including ADHD and motor disorders) raises important challenges for
      understanding these disorders.

PMID- 22141436
TI  - Clinical score for the outcome of external cephalic version: a two-phase
      prospective study.
AB  - AIM: To design a score based on clinical parameters to predict the outcome of
      external cephalic versions (ECVs) at term. MATERIALS AND METHODS: A two-phase
      study was conducted (analysis/design and prospective validation) regarding 1000
      versions performed between March 2002 and November 2010. The variables considered
      in the score were selected based on the results of multiple logistic regression
      models and multiple correspondence analyses published by our group. The
      predictive capacity was estimated through the area under the ROC curve. RESULTS:
      The success rates for ECV in phases 1 and 2 were 52.2 and 51.2%, respectively,
      making the overall success rate 51.7%. The score was designed with the variables
      parity, placental location, breech variety and amount of amniotic fluid giving a
      value for each one. A clinical recommendation, based on the result of the score,
      was the estimated success rate with the 95% confidence interval. The predictive
      capacity of the score for the outcome of ECV at term was 70.1% (95% CI 66.9
      73.4). CONCLUSIONS: A score composed of four easily measurable variables enabled
      us to predict the outcome of ECV at term.

PMID- 22141437
TI  - Glycaemia and correlates of patient-reported outcomes in ACCORD trial
      participants.
AB  - AIMS: Post-hoc evaluation of relationships between first-year change in glycaemic
      control (HbA(1c) ) and change in patient-reported outcomes among ACCORD health
      related quality of life (HRQoL) substudy participants. METHODS: Data from 2053
      glycaemia-trial subjects were analysed. We assessed physical and mental health
      status (36-Item Short Form Health Survey, Version-2), symptom count and severity
      (Diabetes Symptoms Distress Checklist) and treatment satisfaction (Diabetes
      Treatment Satisfaction Questionnaire). Linear mixed models were used to test
      relationships between 1-year changes in HbA(1c) and patient reported outcomes
      sequentially adjusting for correlates (baseline characteristics, baseline patient
      reported outcomes, treatment assignment, frequency of clinical contact and post
      randomization weight change plus new complications). RESULTS: Poorer baseline
      control of HbA(1c) and cardiovascular disease risk factors predicted greater one
      year improvements in treatment satisfaction. Similarly, poorer baseline patient
      reported outcome scores all individually predicted greater 1-year improvement in
      that same outcome. Accounting for baseline and post-randomization characteristics
      and treatment arm, 1-year change in HbA(1c) was unrelated to changes in overall
      physical or mental health; however, every one percentage-point (10.9 mmol/mol)
      reduction in HbA(1c) was associated with lower symptom count (beta = 0.599; P =
      0.012), lower symptom distress (beta = 0.051; P = 0.001), and higher treatment
      satisfaction (beta = -2.514; P < 0.001). CONCLUSIONS: Independent of all relevant
      covariates, better glycaemic control over 1 year was associated with reduced
      patient-reported diabetes symptoms and symptom distress, and increased treatment
      satisfaction, but not overall physical and mental health. Further investigation
      is required to understand the specific psychosocial mechanisms that affect how
      patients value health and treatments.

PMID- 22141438
TI  - Bidirectional cross-sectional and prospective associations between physical
      activity and body composition in adolescence: birth cohort study.
AB  - The aim of this study was to investigate the cross-sectional and prospective
      associations between physical activity and body composition in adolescence. This
      is a prospective study, including 4,103 adolescents belonging to the Pelotas
      (Brazil) 1993 birth cohort, who were followed up at the mean ages of 11.3 and
      14.7 years. Subsample analyses included 511 individuals with accelerometry and
      deuterium dilution data at 13.3 years. Sum of skinfolds at age 11.3 years was
      highly correlated with skinfolds at age 14.7 years (rho = 0.74, P < 0.001). More
      than 85% of participants remained in the same quintile or changed by not more
      than one quintile during the 3.4 year period. Tracking of physical activity was
      considerably lower, although still significant; the correlation was 0.24 (P <
      0.001) and 61.4% of the adolescents moved one or less quintiles. In fully
      adjusted models, no significant cross-sectional or longitudinal associations were
      found between physical activity and body composition, neither in boys nor in
      girls. These null results were confirmed in the 511 individuals with
      accelerometry and deuterium data. We provide evidence of tracking of physical
      activity and particularly body composition during adolescence. Our results do not
      support the hypothesis that physical activity and fatness are strongly related in
      adolescents.

PMID- 22141439
TI  - Urethral catheterization facilitates preradiation fiducial marker placement in
      postprostatectomy patients.
AB  - Surgical absence of the prostate can make placement of fiducial markers
      difficult, because anatomic landmarks are distorted and there is a paucity of
      substantial tissue to hold fast the markers. We describe a method for improving
      the accuracy of fiducial marker placement for the purpose of salvage or adjuvant
      external beam radiation therapy for prostate cancer in patients who have
      undergone radical prostatectomy. To assist with identification of the
      urethrovesical junction and to facilitate placement of the markers, a Foley
      catheter was placed and the balloon was inflated. Gentle traction on the catheter
      seated the balloon at the bladder neck to echographically define the anatomy of
      the urethrovesical junction. Next, a rectal ultrasound probe was inserted into
      the rectum, allowing visualization of the region of the urethrovesical junction.
      Fiducial markers were then placed bilaterally in the detrusor muscle at the
      bladder neck or in the periurethral tissue using the applicator needle. The
      treating radiation oncologist verified that marker placement was suitable for
      assisting with radiation therapy in all cases. Preradiation pelvic imaging
      verified that markers were not in the bladder or urethral lumen, and there were
      no patient complaints of voiding out the markers with urination.

PMID- 22141440
TI  - Sampling assumptions in inductive generalization.
AB  - Inductive generalization, where people go beyond the data provided, is a basic
      cognitive capability, and it underpins theoretical accounts of learning,
      categorization, and decision making. To complete the inductive leap needed for
      generalization, people must make a key ''sampling'' assumption about how the
      available data were generated. Previous models have considered two extreme
      possibilities, known as strong and weak sampling. In strong sampling, data are
      assumed to have been deliberately generated as positive examples of a concept,
      whereas in weak sampling, data are assumed to have been generated without any
      restrictions. We develop a more general account of sampling that allows for an
      intermediate mixture of these two extremes, and we test its usefulness. In two
      experiments, we show that most people complete simple one-dimensional
      generalization tasks in a way that is consistent with their believing in some
      mixture of strong and weak sampling, but that there are large individual
      differences in the relative emphasis different people give to each type of
      sampling. We also show experimentally that the relative emphasis of the mixture
      is influenced by the structure of the available information. We discuss the
      psychological meaning of mixing strong and weak sampling, and possible extensions
      of our modeling approach to richer problems of inductive generalization.

PMID- 22141441
TI  - Sinophysis and Pseudophalacroma are distantly related to typical Dinophysoid
      dinoflagellates (Dinophysales, Dinophyceae).
AB  - Dinophysoid dinoflagellates are usually considered a large monophyletic group.
      Large subunit and small subunit (SSU) rDNA phylogenies suggest a basal position
      for Amphisoleniaceae (Amphisolenia,Triposolenia) with respect to two sister
      groups, one containing most Phalacroma species plus Oxyphysis and the other
      Dinophysis,Ornithocercus, Dinophysoid dinoflagellates are usually considered a
      large monophyletic group. Large subunit and small subunit (SSU) rDNA phylogenies
      suggest a basal position for Amphisoleniaceae (Amphisolenia,Triposolenia) with
      respect to two sister groups, one containing most Phalacroma species plus
      Oxyphysis and the other Dinophysis,Ornithocercus, Histioneis,Citharistes and some
      Phalacroma species. We provide here new SSU rDNA sequences of Pseudophalacroma
      (pelagic) and Sinophysis (the only benthic dinophysoid genus). Molecular
      phylogenies support that they are very divergent with respect to the main clade
      of Dinophysales. Additional molecular markers of these two key genera are needed
      to elucidate the evolutionary relations among the dinophysoid dinoflagellates.
      Histioneis,Citharistes and some Phalacroma species. We provide here new SSU rDNA
      sequences of Pseudophalacroma (pelagic) and Sinophysis (the only benthic
      dinophysoid genus). Molecular phylogenies support that they are very divergent
      with respect to the main clade of Dinophysales. Additional molecular markers of
      these two key genera are needed to elucidate the evolutionary relations among the
      dinophysoid dinoflagellates.

PMID- 22141443
TI  - Determination of polymer additives-antioxidants and ultraviolet (UV) absorbers by
      high-performance liquid chromatography coupled with UV photodiode array detection
      in food simulants.
AB  - An analytical method for the quantitative determination of migration levels of
      polymer additives such as antioxidants and UV absorbers in food packages by high
      performance liquid chromatography coupled with UV-vis photodiode array detection
      has been developed. The pretreatment step involved solid-phase extraction with
      silica C18 cartridges. The analytical method showed good linearity, presenting
      regression coefficients (R(2)) >= 0.9990 for all compounds. This optimized method
      was also validated with respect to precision, reproducibility, stability, and
      accuracy. The limits of detection and quantification were between 0.09 and 1.72
      MUg mL(-1) and between 0.20 and 5.64 MUg mL(-1) for 12 analytes, respectively.
      Recoveries were in the range of 67.48 and 108.55%, with relative standard
      deviations between 2.76 and 9.81%. Migration levels of antioxidants and UV
      absorbers were determined. Butylated hydroxyanisole, 2,6-di-tert-butyl-4
      methylphenol (BHT), 2,4-di-tert-butylphenol, Cyanox 2246, Irganox 1035, Tinuvin
      326, Tinuvin 328, Irganox 1010, and Irganox 1330 were detected; BHT and Cyanox
      2246 were at higher levels than the specific migration levels in some food
      simulants.

PMID- 22141445
TI  - Structural characterization of drug-like compounds by ion mobility mass
      spectrometry: comparison of theoretical and experimentally derived nitrogen
      collision cross sections.
AB  - We present the use of drug-like molecules as a traveling wave (T-wave) ion
      mobility (IM) calibration sample set, covering the m/z range of 122.1-609.3, the
      nitrogen collision cross-section (Omega(N(2))) range of 124.5-254.3 A(2) and the
      helium collision cross-section (Omega(He)) range of 63.0-178.8 A(2). Absolute
      Omega(N(2)) and Omega(He) values for the drug-like calibrants and two
      diastereomers were measured using a drift-tube instrument with radio frequency
      (RF) ion confinement. T-wave drift-times for the protonated diastereomers
      betamethasone and dexamethasone are reproducibly different. Calibration of these
      drift-times yields T-wave Omega(N(2)) values of 189.4 and 190.4 A(2),
      respectively. These results demonstrate the ability of T-wave IM spectrometry to
      differentiate diastereomers differing in Omega(N(2)) value by only 1 A(2), even
      though the resolution of these IM experiments were ~40 (Omega/DeltaOmega).
      Demonstrated through density functional theory optimized geometries and ionic
      electrostatic surface potential analysis, the small but measurable mobility
      difference between the two diastereomers is mainly due to short-range van der
      Waals interactions with the neutral buffer gas and not long-range charge-induced
      dipole interactions. The experimental RF-confining drift-tube and T-wave
      Omega(N(2)) values were also evaluated using a nitrogen based trajectory method,
      optimized for T-wave operating temperature and pressures, incorporating
      additional scaling factors to the Lennard-Jones potentials. Experimental
      Omega(He) values were also compared to the original and optimized helium based
      trajectory methods.

PMID- 22141444
TI  - A longitudinal analysis of circulating stress-related proteins and chronic
      ethanol self-administration in cynomolgus macaques.
AB  - BACKGROUND: Alcoholics have alterations in endocrine and immune functions and
      increased susceptibility to stress-related disorders. A longitudinal analysis of
      chronic ethanol intake on homeostatic mechanisms is, however, incompletely
      characterized in primates. METHODS: Plasma proteins (n = 60; Luminex) and
      hormones (adrenocorticotropic hormone [ACTH]; cortisol) were repeatedly measured
      in adult male cynomolgus monkeys (Macaca fascicularis, n = 10) during a 32-month
      experimental protocol at baseline, during induction of water and ethanol (4% w/v
      in water) self-administration, after 4 months, and after 12 months of 22-hour
      daily concurrent access to ethanol and water. RESULTS: Significant changes were
      observed in ACTH, cortisol, and 45/60 plasma proteins: a majority (28/45) were
      suppressed as a function of ethanol self-administration, 8 proteins were
      elevated, and 9 showed biphasic changes. Cortisol and ACTH were greatest during
      induction, and correlations between these hormones and plasma proteins varied
      across the experiment. Pathway analyses implicated nuclear factor kappa-light
      chain-enhancer of activated B cells (NF-kappaB) and Janus kinase (JAK)/signal
      transducer and activator of transcription (STAT) as possible mediators of ethanol
      induced effects on immune-related proteins in primates. CONCLUSIONS: Chronic
      ethanol consumption in primates leads to an allostatic state of physiological
      compromise with respect to circulating immune- and stress-related proteins in NF
      kappaB- and STAT/JAK-related pathways in correlation with altered endocrine
      activity.

PMID- 22141446
TI  - Reporting of participant flow diagrams in published reports of randomized trials.
AB  - BACKGROUND: Reporting of the flow of participants through each stage of a
      randomized trial is essential to assess the generalisability and validity of its
      results. We assessed the type and completeness of information reported in CONSORT
      (Consolidated Standards of Reporting Trials) flow diagrams published in current
      reports of randomized trials. METHODS: A cross sectional review of all primary
      reports of randomized trials which included a CONSORT flow diagram indexed in
      PubMed core clinical journals (2009). We assessed the proportion of parallel
      group trial publications reporting specific items recommended by CONSORT for
      inclusion in a flow diagram. RESULTS: Of 469 primary reports of randomized
      trials, 263 (56%) included a CONSORT flow diagram of which 89% (237/263) were
      published in a CONSORT endorsing journal. Reports published in CONSORT endorsing
      journals were more likely to include a flow diagram (62%; 237/380 versus 29%;
      26/89). Ninety percent (236/263) of reports which included a flow diagram had a
      parallel group design, of which 49% (116/236) evaluated drug interventions, 58%
      (137/236) were multicentre, and 79% (187/236) compared two study groups, with a
      median sample size of 213 participants. Eighty-one percent (191/236) reported the
      overall number of participants assessed for eligibility, 71% (168/236) the number
      excluded prior to randomization and 98% (231/236) the overall number randomized.
      Reasons for exclusion prior to randomization were more poorly reported. Ninety
      four percent (223/236) reported the number of participants allocated to each arm
      of the trial. However, only 40% (95/236) reported the number who actually
      received the allocated intervention, 67% (158/236) the number lost to follow up
      in each arm of the trial, 61% (145/236) whether participants discontinued the
      intervention during the trial and 54% (128/236) the number included in the main
      analysis. CONCLUSIONS: Over half of published reports of randomized trials
      included a diagram showing the flow of participants through the trial. However,
      information was often missing from published flow diagrams, even in articles
      published in CONSORT endorsing journals. If important information is not reported
      it can be difficult and sometimes impossible to know if the conclusions of that
      trial are justified by the data presented.

PMID- 22141448
TI  - Synthesis of polymer-derived ceramic Si(B)CN-carbon nanotube composite by
      microwave-induced interfacial polarization.
AB  - We demonstrate synthesis of a polymer-derived ceramic (PDC)-multiwall carbon
      nanotube (MWCNT) composite using microwave irradiation at 2.45 GHz. The process
      takes about 10 min of microwave irradiation for the polymer-to-ceramic
      conversion. The successful conversion of polymer coated carbon nanotubes to
      ceramic composite is chemically ascertained by Fourier transform-infrared and X
      ray photoelectron spectroscopy and physically by thermogravimetric analysis and
      transmission electron microscopy characterization. Frequency dependent dielectric
      measurements in the S-Band (300 MHz to 3 GHz) were studied to quantify the extent
      of microwave-CNT interaction and the degree of selective heating available at the
      MWCNT-polymer interface. Experimentally obtained return loss of the incident
      microwaves in the specimen explains the reason for heat generation. The
      temperature-dependent permittivity of polar molecules further strengthens the
      argument of internal heat generation.

PMID- 22141447
TI  - A randomized trial of an intervention to improve use and adherence to effective
      coronary heart disease prevention strategies.
AB  - BACKGROUND: Efficacious strategies for the primary prevention of coronary heart
      disease (CHD) are underused, and, when used, have low adherence. Existing efforts
      to improve use and adherence to these efficacious strategies have been so
      intensive that they are impractical for clinical practice. METHODS: We conducted
      a randomized trial of a CHD prevention intervention (including a computerized
      decision aid and automated tailored adherence messages) at one university general
      internal medicine practice. After obtaining informed consent and collecting
      baseline data, we randomized patients (men and women age 40-79 with no prior
      history of cardiovascular disease) to either the intervention or usual care. We
      then saw them for two additional study visits over 3 months. For intervention
      participants, we administered the decision aid at the primary study visit (1 week
      after baseline visit) and then mailed 3 tailored adherence reminders at 2, 4, and
      6 weeks. We assessed our outcomes (including the predicted likelihood of angina,
      myocardial infarction, and CHD death over 10 years (CHD risk) and self-reported
      adherence) between groups at 3 month follow-up. Data collection occurred from
      June 2007 through December 2009. All study procedures were IRB approved. RESULTS:
      We randomized 160 eligible patients (81 intervention; 79 control) and followed
      96% to study conclusion. Mean predicted CHD risk at baseline was 11.3%. The
      intervention increased self-reported adherence to chosen risk reducing strategies
      by 25 percentage points (95% CI 8% to 42%), with the biggest effect for aspirin.
      It also changed predicted CHD risk by -1.1% (95% CI -0.16% to -2%), with a larger
      effect in a pre-specified subgroup of high risk patients. CONCLUSION: A
      computerized intervention that involves patients in CHD decision making and
      supports adherence to effective prevention strategies can improve adherence and
      reduce predicted CHD risk.

PMID- 22141450
TI  - Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran
      etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial:
      a rebuttal.

PMID- 22141451
TI  - Different characteristics of reactive oxygen species production by human
      keratinocyte cell line cells in response to allergens and irritants.
AB  - Keratinocytes mount immune responses through the secretion of a variety of
      inflammatory cytokines, soluble proteins and reactive oxygen species (ROS).
      However, the role of ROS in keratinocytes in response to allergens and irritants
      has not yet been elucidated. In this study, we investigated the (i) ROS
      production; (ii) potential sites of ROS production; (iii) expression of cell
      surface molecules; (iv) secretion of cytokines; and (v) ROS-dependent protein
      carbonylation in chemical-treated human keratinocyte cell line (HaCaT) cells.
      Treatment of HaCaT cells with 2,4-dinitrochlorobenzene (DNCB) and benzalkonium
      chloride (BKC) increased ROS levels in a time- and dose-dependent manner, as
      determined with dichlorodihydrofluorescein diacetate (CM-H(2) DCFDA), without
      reducing cell viability. Potential sources of ROS production were evaluated with
      pretreatment of diphenylene iodonium (DPI), an inhibitor of nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase; rotenone, an inhibitor of the
      mitochondrial electron transport chain complex or allopurinol, a xanthine oxidase
      inhibitor. The DNCB-induced ROS was related to both NADPH oxidase and
      mitochondrial electron transport chain complex. Conversely, BKC-induced ROS was
      related to NADPH oxidase only. Western blotting using an anti-DNP antibody
      revealed ROS-dependent protein carbonylation in response to DNCB but not BKC.
      Both DNCB and BKC increased the secretion of IL-1alpha from HaCaT cells; however,
      ROS production as well as other changes, except DNCB-induced secretion of IL
      1alpha, was not inhibited by antioxidants. Although the role of ROS in
      keratinocytes in response to chemicals was inconclusive, our results suggest that
      the characteristics of ROS produced by keratinocytes in response to chemicals
      might differ.

PMID- 22141452
TI  - Why have guidelines at all? A critical perspective.

PMID- 22141454
TI  - Genotyping of Streptococcus thermophilus strains isolated from traditional
      Egyptian dairy products by sequence analysis of the phosphoserine phosphatase
      (serB) gene with phenotypic characterizations of the strains.
AB  - AIMS: To develop a new, simplified genotyping method for examining the genetic
      diversity of Streptococcus thermophilus strains isolated from traditional
      Egyptian fermented dairy products and to characterize phenotypic traits of those
      strains related to their potential use in bioprocessing applications. METHODS AND
      RESULTS: A novel, simplified approach was developed for genotyping Strep.
      thermophilus involving the analysis of nucleotide sequence variations within a
      housekeeping gene encoding the phosphoserine phosphatase (SerB). Using this
      method, it was possible to identify ten genotypes involving diverse serB alleles
      among 54 Strep. thermophilus isolates cultured from Egyptian dairy products.
      These isolates harboured five de novo serB alleles that have not been detected in
      other Strep. thermophilus strains, deposited in a multilocus sequence typing
      (MLST) database. To assess distinct genotypes of the organism with phenotypic
      traits relevant to their potential use in industry, Strep. thermophilus strains
      were all subjected to a series of phenotypic characterizations. The strains were
      found to exhibit phenotypic diversity in terms of their ability to ferment
      lactose and galactose, express urease activity, produce exopolysaccharides and
      develop acidity. CONCLUSIONS: The analysis of nucleotide sequence variations
      within the serB gene could serve as a suitable tool for probing diverse genotypes
      of Strep. thermophilus. Streptococcus thermophilus isolates associated with
      traditional Egyptian dairy products show high degree of genetic and phenotypic
      diversity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a novel,
      simplified procedure based on serB nucleotide sequencing for genotyping Strep.
      thermophilus. It also provides a pool of phenotypically diverse Strep.
      thermophilus cultures, from which certain strains could be selected for use in
      bioprocessing applications including the preparation of fermented dairy products.

PMID- 22141453
TI  - Factors associated with time to colposcopy after abnormal Pap testing in HIV
      infected women.
AB  - BACKGROUND: HIV-infected women are at increased risk for cervical dysplasia and
      require timely follow-up after an abnormal Papanicolaou (Pap) test. METHODS: This
      retrospective cohort study assessed the proportion of HIV-infected women with
      colposcopic evaluation after an abnormal Pap test. Time to colposcopy within 12
      months after an abnormal Pap test was assessed with univariate and multivariate
      Cox proportional hazard modeling in a diverse cohort of HIV-infected women
      between October 1, 2003, and September 30, 2007. RESULTS: One hundred seventy
      seven subjects had an abnormal Pap test: 22 high-grade intraepithelial lesion
      (HSIL; 12%), 120 low-grade squamous intraepithelial lesion (LSIL; 68%), and 35
      atypical squamous cells of undetermined significance, human papillomavirus
      positive (20%). One hundred twenty (68%) had follow-up colposcopy by 1 year.
      Decreased time to follow-up was associated with being married (HR 3.5, 95% CI 1.9
      6.2), high school graduate or higher education level (HR 1.7, CI 1.2-2.6), HSIL
      Pap results (HR 2.8, CI 1.3-6.2), Pap testing performed by HIV nurse practitioner
      versus gynecology clinic (HR 1.7, 1.1-2.7), and CD4 count >=500 cells/mm(3) (HR
      1.8, CI 1.2-2.8), after adjusting for age, race/ethnicity, and LSIL Pap result.
      Private insurance was associated with decreased time to colposcopy in unadjusted,
      but not multivariate analysis. Drug use was not associated with time to follow-up
      colposcopy. CONCLUSIONS: Almost one third of HIV-infected women did not have a
      follow-up colposcopy by 12 months after an abnormal Pap test. Since HIV-infected
      women are at particularly high risk for cervical cancer, these results are
      unacceptably poor. Identification of the barriers to appropriate follow-up and
      targeted interventions are necessary to improve timely follow-up for cytologic
      abnormalities in this high-risk population.

PMID- 22141455
TI  - Examination of neurological subtle signs in ADHD as a clinical tool for the
      diagnosis and their relationship to spatial working memory.
AB  - BACKGROUND:   Neurological subtle signs (NSS) are minor neurological
      abnormalities that have been shown to be increased in a number of
      neurodevelopmental conditions. For attention deficit/hyperactivity disorder
      (ADHD), it remains unclear whether NSS may aid the clinical diagnostic process.
      METHODS:   This study explored the association of total and specific domains of
      NSS in 1,055 children and adolescents with ADHD compared to 130 age-matched
      typically developing participants; the relationship between NSS and Spatial
      Working Memory (SWM) as a cognitive process integrally involved in ADHD was also
      assessed. To determine the diagnostic and predictive efficiency of NSS, a
      receiver operating curve analysis was performed and the area under the curve
      (AUC) quantified. The best discriminant points for differentiating between ADHD
      and typically developing participants and the predictive power of NSS for SWM
      impairment in ADHD young people were also calculated. RESULTS:   Area under the
      curves for total NSS, smoothness/accuracy, cerebellar signs and choreo-athetoid
      movements scores were considered good (.84, .79, .74 and .73 respectively), and
      the results remained after controlling for gender and IQ. A total score of 13 or
      over on the Scored Developmental Neurological Examination proved to be a good
      threshold point for differentiating between the ADHD and typically developing
      participants. For ADHD children, the AUC of total NSS to distinguish between
      those below 25th and above 75th percentile were .77 and .73 for Spatial Span and
      for Between Search Errors respectively (the two SWM-dependent measures examined).
      CONCLUSIONS:   This study provides evidence suggesting that NSS may aid the
      clinical evaluation of a child or adolescent with ADHD. In children and
      adolescents with ADHD, NSS are associated with difficulties in SWM, specifically
      the Spatial Span and Between Search Error components.

PMID- 22141456
TI  - Effects of relaxin on relapse and periodontal tissue remodeling after
      experimental tooth movement in rats.
AB  - The relapse of teeth that have moved during orthodontic treatment is a major
      clinical issue with respect to the goals of successful treatment. Relaxin has an
      influence on many physiologic processes, such as collagen turnover. In this
      study, we determined the effects of relaxin on the relapse and remodeling of
      periodontal tissue after experimental tooth movement in rats, and we explored the
      molecular mechanism underlying these processes. To induce experimental tooth
      movement in rats, 10 g of orthodontic force was applied to the molars. After 14
      days, the spring was removed, and then animals began receiving relaxin at a dose
      of 500 ng/ml for 1 week. The results were evaluated by micro-computed tomography
      and immunofluorescence staining. In addition, the effects of matrix
      metalloproteinase (MMP)-1 and MMP-8 production were investigated in human
      periodontal ligament (hPDL) cells in vitro. The expression of MMP-1 and MMP-8 was
      analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent
      assay. Furthermore, we demonstrated the signaling pathways involved in relaxin
      regulated MMPs expression. The relapse distances and percentages were
      significantly decreased in the experimental group compared with the controls in
      vivo. A double-immunofluorescence analysis for Col-I/MMP-1 and Col-I/MMP-8
      detected the expression of relaxin in the PDL. Relaxin significantly increased
      the MMP-1 and MMP-8 expression in a time-dependent manner in hPDL cells in vitro.
      Furthermore, a p38 inhibitor (SB203580) significantly inhibited the MMP-1 and MMP
      8 expression. Our results indicated that relaxin modulates the collagen
      metabolism, and this hormone may therefore be useful to prevent orthodontic
      relapse following orthodontic treatment.

PMID- 22141457
TI  - HCN channels in the heart: lessons from mouse mutants.
AB  - Hyperpolarization-activated cation channels generate the I(f)  current in the
      heart. In the sino-atrial node (SAN), I(f)  is thought to play an essential role
      in setting the heart rate and mediating its autonomic control. This review
      focuses on the role of I(f)  in pacemaking and non-pacemaking cardiomyocytes and
      the resulting therapeutic implications. HCN4 represents the principal isoform
      underlying sino-atrial I(f) , but other isoforms may also be of importance. To
      examine the functional role of cardiac channels, several mouse mutants, most of
      them targeting HCN4, have been generated by different groups. Unexpectedly, these
      lines display greatly different and as yet unexplained phenotypes. We provide an
      overview about these HCN mutants and suggest an interpretation of the functional
      significance of I(f)  in the SAN in light of these studies. HCN channels are also
      present in ventricular myocytes, and an up-regulation of I(f)  in the
      hypertrophic and failing heart may contribute to arrhythmogenesis. Inhibition of
      I(f)  by HCN channel blockers is a novel approach in the treatment of cardiac
      disorders, and ivabradine is approved for treatment of stable angina pectoris.
      Remarkably, a recent clinical trial assessing this substance in heart failure
      showed a significantly improved outcome. The mechanism underlying this beneficial
      effect is not yet clear and might lie beyond heart rate slowing. Thus, the
      growing knowledge about cardiac HCN channels will undoubtedly promote the
      development of the promising class of HCN channel blockers.

PMID- 22141458
TI  - Does a diabetes annual review make a difference?
AB  - AIMS: To determine whether a diabetes annual review, independently of other care
      processes, is followed by improved patient clinical measurements. METHODS: Audits
      conducted independently of the diabetes annual review were analysed for a time
      trend in patient clinical measures. An interaction variable between the review
      and the year of audit was used to test for a change in gradient before and after
      a diabetes annual review. Each patient formed their own control. RESULTS: The
      data included 9471 audits on 3397 patients from 92 practices, and diabetes annual
      reviews from 2003 to mid-2008. Percentages of patients with raised HbA(1c) ,
      systolic blood pressure and lipids improved from first to last audit. Predicted
      means after a diabetes annual review for HbA(1c) decreased by 0.13% (1.0
      mmol/mol), for HDL cholesterol increased by 0.04 mmol/L and for triglyceride
      decreased by 0.2 mmol/L. Predicted systolic and diastolic blood pressure, total
      cholesterol and urinary albumin:creatinine ratio did not change significantly.
      CONCLUSIONS: Metabolic control improved over time but this was largely
      independently of the diabetes annual review, which appears to add little clinical
      value to existing New Zealand general practice care processes. Currently, general
      practitioners are paid to undertake a diabetes annual review and report the
      measurements collected. We would argue that payment needs to be directed to
      demonstrating appropriate changes in clinical management or achieving meaningful
      clinical goals, and that the annual review results should be part of systematic
      feedback to general practitioners, particularly directed at clinical inertia.

PMID- 22141459
TI  - Developing the Coach Analysis and Intervention System (CAIS): establishing
      validity and reliability of a computerised systematic observation instrument.
AB  - We outline the evolution of a computerised systematic observation tool and
      describe the process for establishing the validity and reliability of this new
      instrument. The Coach Analysis and Interventions System (CAIS) has 23 primary
      behaviours related to physical behaviour, feedback/reinforcement, instruction,
      verbal/non-verbal, questioning and management. The instrument also analyses
      secondary coach behaviour related to performance states, recipient, timing,
      content and questioning/silence. The CAIS is a multi-dimensional and multi-level
      mechanism able to provide detailed and contextualised data about specific
      coaching behaviours occurring in complex and nuanced coaching interventions and
      environments that can be applied to both practice sessions and competition.

PMID- 22141460
TI  - 2-Amino-3-cyanopyridine derivatives as carbonic anhydrase inhibitors.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous enzymes that catalyze the
      hydration of CO(2) to bicarbonate and protons. Inhibition of CAs has been
      clinically exploited for the treatment of various classes of diseases for
      decades, but investigating new classes of inhibitors continues to be important.
      We have synthesized a series of 2-amino-3-cyano-4-heteroaryl (5a-l) compounds and
      characterized the structures by NMR, IR and elemental analyses. We tested the
      ability of these compounds to inhibit two metalloenzyme human carbonic anhydrase
      (hCA, EC 4.2.1.1) isozymes, hCA I and hCA II. Compounds 5d and 5b showed the best
      inhibition activity against hCA I (IC(50): 33 and 34 uM, respectively), and
      compound 5d showed the best activity against hCA II (IC(50): 56 uM).

PMID- 22141461
TI  - Navigation assistance: a trade-off between wayfinding support and configural
      learning support.
AB  - Current GPS-based mobile navigation assistance systems support wayfinding, but
      they do not support learning about the spatial configuration of an environment.
      The present study examined effects of visual presentation modes for navigation
      assistance on wayfinding accuracy, route learning, and configural learning.
      Participants (high-school students) visited a university campus for the first
      time and took a predefined assisted tour. In Experiment 1 (n = 84, 42 females), a
      presentation mode showing wayfinding information from eye-level was contrasted
      with presentation modes showing wayfinding information included in views that
      provided comprehensive configural information. In Experiment 2 (n = 48, 24
      females), wayfinding information was included in map fragments. A presentation
      mode which always showed north on top of the device was compared with a mode
      which rotated according to the orientation of the user. Wayfinding accuracy
      (deviations from the route), route learning, and configural learning (direction
      estimates, sketch maps) were assessed. Results indicated a trade-off between
      wayfinding and configural learning: Presentation modes providing comprehensive
      configural information supported the acquisition of configural knowledge at the
      cost of accurate wayfinding. The route presentation mode supported wayfinding at
      the cost of configural knowledge acquisition. Both presentation modes based on
      map fragments supported wayfinding. Individual differences in visual-spatial
      working memory capacity explained a considerable portion of the variance in
      wayfinding accuracy, route learning, and configural learning. It is concluded
      that learning about an unknown environment during assisted navigation is based on
      the integration of spatial information from multiple sources and can be supported
      by appropriate visualization.

PMID- 22141462
TI  - RACE/A: an architectural account of the interactions between learning, task
      control, and retrieval dynamics.
AB  - This article discusses how sequential sampling models can be integrated in a
      cognitive architecture. The new theory Retrieval by Accumulating Evidence in an
      Architecture (RACE/A) combines the level of detail typically provided by
      sequential sampling models with the level of task complexity typically provided
      by cognitive architectures. We will use RACE/A to model data from two variants of
      a picture-word interference task in a psychological refractory period design.
      These models will demonstrate how RACE/A enables interactions between sequential
      sampling and long-term declarative learning, and between sequential sampling and
      task control. In a traditional sequential sampling model, the onset of the
      process within the task is unclear, as is the number of sampling processes.
      RACE/A provides a theoretical basis for estimating the onset of sequential
      sampling processes during task execution and allows for easy modeling of multiple
      sequential sampling processes within a task.

PMID- 22141463
TI  - Cutaneous horn: a malignant lesion? A brief review of the literature.

PMID- 22141464
TI  - Tools for studying dry-cured ham processing by using computed tomography.
AB  - An accurate knowledge and optimization of dry-cured ham elaboration processes
      could help to reduce operating costs and maximize product quality. The
      development of nondestructive tools to characterize chemical parameters such as
      salt and water contents and a(w) during processing is of special interest. In
      this paper, predictive models for salt content (R(2) = 0.960 and RMSECV = 0.393),
      water content (R(2) = 0.912 and RMSECV = 1.751), and a(w) (R(2) = 0.906 and
      RMSECV = 0.008), which comprise the whole elaboration process, were developed.
      These predictive models were used to develop analytical tools such as
      distribution diagrams, line profiles, and regions of interest (ROIs) from the
      acquired computed tomography (CT) scans. These CT analytical tools provided
      quantitative information on salt, water, and a(w) in terms of content but also
      distribution throughout the process. The information obtained was applied to two
      industrial case studies. The main drawback of the predictive models and CT
      analytical tools is the disturbance that fat produces in water content and a(w)
      predictions.

PMID- 22141466
TI  - Amorphous hierarchical porous GeO(x) as high-capacity anodes for Li ion batteries
      with very long cycling life.
AB  - Many researchers have focused in recent years on resolving the crucial problem of
      capacity fading in Li ion batteries when carbon anodes are replaced by other
      group-IV elements (Si, Ge, Sn) with much higher capacities. Some progress was
      achieved by using different nanostructures (mainly carbon coatings), with which
      the cycle numbers reached 100-200. However, obtaining longer stability via a
      simple process remains challenging. Here we demonstrate that a nanostructure of
      amorphous hierarchical porous GeO(x) whose primary particles are ~3.7 nm diameter
      has a very stable capacity of ~1250 mA h g(-1) for 600 cycles. Furthermore, we
      show that a full cell coupled with a Li(NiCoMn)(1/3)O(2) cathode exhibits high
      performance.

PMID- 22141467
TI  - Event-specific enhancement of memory via brief electrical stimulation to the
      basolateral complex of the amygdala in rats.
AB  - The basolateral complex of the amygdala (BLA) modulates memory for emotional
      events, and direct activation of the BLA following a learning session can enhance
      subsequent memory. Yet optimal enhancement of episodic memory during emotional
      events would likely require that BLA activation occur close in time to the event
      and to be brief enough to target specific memories if some events are to be
      remembered better than others. In the present study, rats were given a novel
      object recognition memory task in which initial encounters with some of the
      objects were immediately followed by brief electrical stimulation of the BLA, and
      these objects were remembered better one day later as compared to objects for
      which the initial encounter was not followed by stimulation. The results
      indicated that BLA stimulation can enhance memory for individual events, a
      necessary ability for the BLA to modulate episodic memory effectively.

PMID- 22141468
TI  - Stress-induced cortisol facilitates threat-related decision making among police
      officers.
AB  - Previous research suggests that cortisol can affect cognitive functions such as
      memory, decision making, and attentiveness to threat-related cues. Here, we
      examine whether increases in cortisol, brought on by an acute social stressor,
      influence threat-related decision making. Eighty-one police officers completed a
      standardized laboratory stressor and then immediately completed a computer
      simulated decision-making task designed to examine decisions to accurately shoot
      or not shoot armed and unarmed Black and White targets. Results indicated that
      police officers who had larger cortisol increases to the social-stress task
      subsequently made fewer errors when deciding to shoot armed Black targets
      relative to armed White targets, suggesting that hypothalamic pituitary adrenal
      (HPA) activation may exacerbate vigilance for threat cues. We conclude with a
      discussion of the implications of threat-initiated decision making.

PMID- 22141465
TI  - Differential effects of single versus repeated alcohol withdrawal on the
      expression of endocannabinoid system-related genes in the rat amygdala.
AB  - BACKGROUND: Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol
      (2-AG) exert important regulatory influences on neuronal signaling, participate
      in short- and long-term forms of neuroplasticity, and modulate stress responses
      and affective behavior in part through the modulation of neurotransmission in the
      amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol
      dependence is associated with dysregulated amygdalar function, stress
      responsivity, and affective control. METHODS: The consequence of long-term
      alcohol consumption on the expression of genes related to endocannabinoid
      signaling was investigated using quantitative RT-PCR analyses of amygdala tissue.
      Two groups of ethanol (EtOH)-exposed rats were generated by maintenance on an
      EtOH liquid diet (10%): the first group received continuous access to EtOH for 15
      days, whereas the second group was given intermittent access to the EtOH diet (5
      d/wk for 3 weeks). Control subjects were maintained on an isocaloric EtOH-free
      liquid diet. To provide an initial profile of acute withdrawal, amygdala tissue
      was harvested following either 6 or 24 hours of EtOH withdrawal. RESULTS: Acute
      EtOH withdrawal was associated with significant changes in mRNA expression for
      various components of the endogenous cannabinoid system in the amygdala.
      Specifically, reductions in mRNA expression for the primary clearance routes for
      anandamide and 2-AG (fatty acid amide hydrolase [FAAH] and monoacylglycerol
      lipase [MAGL], respectively) were evident, as were reductions in mRNA expression
      for CB(1) , CB(2) , and GPR55 receptors. Although similar alterations in FAAH
      mRNA were evident following either continuous or intermittent EtOH exposure,
      alterations in MAGL and cannabinoid receptor-related mRNA (e.g., CB(1) , CB(2) ,
      GPR55) were more pronounced following intermittent exposure. In general, greater
      withdrawal-associated deficits in mRNA expression were evident following 24
      versus 6 hours of withdrawal. No significant changes in mRNA expression for
      enzymes involved in 2-AG biosynthesis (e.g., diacylglicerol lipase-alpha/beta)
      were found in any condition. CONCLUSIONS: These findings suggest that EtOH
      dependence and withdrawal are associated with dysregulated endocannabinoid
      signaling in the amygdala. These alterations may contribute to withdrawal-related
      dysregulation of amygdalar neurotransmission.

PMID- 22141469
TI  - Interplay of oxytocin, vasopressin, and sex hormones in the regulation of social
      recognition.
AB  - Social Recognition is a fundamental skill that forms the basis of behaviors
      essential to the proper functioning of pair or group living in most social
      species. We review here various neurobiological and genetic studies that point to
      an interplay of oxytocin (OT), arginine-vasopressin (AVP), and the gonadal
      hormones, estrogens and testosterone, in the mediation of social recognition.
      Results of a number of studies have shown that OT and its actions at the medial
      amygdala seem to be essential for social recognition in both sexes. Estrogens
      facilitate social recognition, possibly by regulating OT production in the
      hypothalamus and the OT receptors at the medial amygdala. Estrogens also affect
      social recognition on a rapid time scale, likely through nongenomic actions. The
      mechanisms of these rapid effects are currently unknown but available evidence
      points at the hippocampus as the possible site of action. Male rodents seem to be
      more dependent on AVP acting at the level of the lateral septum for social
      recognition than female rodents. Results of various studies suggest that
      testosterone and its metabolites (including estradiol) influence social
      recognition in males primarily through the AVP V1a receptor. Overall, it appears
      that gonadal hormone modulation of OT and AVP regulates and fine tunes social
      recognition and those behaviors that depend upon it (e.g., social bonds, social
      hierarchies) in a sex specific manner. This points at an important role for these
      neuroendocrine systems in the regulation of the sex differences that are evident
      in social behavior and of sociality as a whole.

PMID- 22141470
TI  - Long-term replacement of estrogen in combination with medroxyprogesterone acetate
      improves acquisition of an alternation task in middle-aged female rats.
AB  - Studies have shown that ovarian hormones protect against some of the cognitive
      deficits associated with aging. Although much of the literature in rodents has
      focused on hippocampal dependent tasks, studies suggest that tasks dependent on
      the prefrontal cortex are also influenced by ovarian hormones. The present study
      investigated the effects of ovarian hormone treatment during aging on a delayed
      alternation t-maze. Female Long Evans hooded rats were ovariectomized at middle
      age (11-12 months) and placed in 1 of 5 treatment groups: no replacement, chronic
      estradiol (E(2)), cyclic E(2), chronic E(2) and progesterone, or chronic E(2) and
      medroxyprogesterone acetate (MPA). Following 6 months of hormone treatment,
      animals were trained to alternate in a t-maze. After reaching criterion, a series
      of delays from 5 to 90 s were introduced in random order. Rats receiving E(2)
      with MPA reached criterion significantly faster than animals not receiving
      treatment and those who received chronic or cyclic E(2) only. There was a
      nonsignificant trend for animals receiving E(2) and progesterone to reach
      criterion in fewer sessions than animals receiving E(2) only. Mode of
      administration, cyclic or chronic, did not affect performance. Hormones did not
      affect performance on the delayed alternation. This study, in combination with
      previous research, indicates that hormone effects cannot be generalized across
      tasks, age, or duration, and long-term estrogen in combination with MPA can be
      beneficial for some tasks.

PMID- 22141471
TI  - Visualisation to enhance biomechanical tuning of ankle-foot orthoses (AFOs) in
      stroke: study protocol for a randomised controlled trial.
AB  - BACKGROUND: There are a number of gaps in the evidence base for the use of ankle
      foot orthoses for stroke patients. Three dimensional motion analysis offers an
      ideal method for objectively obtaining biomechanical gait data from stroke
      patients, however there are a number of major barriers to its use in routine
      clinical practice. One significant problem is the way in which the biomechanical
      data generated by these systems is presented. Through the careful design of
      bespoke biomechanical visualisation software it may be possible to present such
      data in novel ways to improve clinical decision making, track progress and
      increase patient understanding in the context of ankle-foot orthosis tuning.
      METHODS: A single-blind randomised controlled trial will be used to compare the
      use of biomechanical visualisation software in ankle-foot orthosis tuning against
      standard care (tuning using observation alone). Participants (n = 70) will have
      experienced a recent hemiplegia (1-12 months) and will be identified by their
      care team as being suitable candidates for a rigid ankle-foot orthosis. The
      primary outcome measure will be walking velocity. Secondary outcome measures
      include; lower limb joint kinematics (thigh and shank global orientations) &
      kinetics (knee and hip flexion/extension moments, ground reaction force FZ2 peak
      magnitude), step length, symmetry ratio based on step length, Modified Ashworth
      Scale, Modified Rivermead Mobility Index and EuroQol (EQ-5D). Additional
      qualitative measures will also be taken from participants (patients and
      clinicians) at the beginning and end of their participation in the study. The
      main aim of the study is to determine whether or not the visualisation of
      biomechanical data can be used to improve the outcomes of tuning ankle-foot
      orthoses for stroke patients. DISCUSSION: In addition to answering the primary
      research question the broad range of measures that will be taken during this
      study are likely to contribute to a wider understanding of the impact of ankle
      foot orthoses on the lives of stroke patients. TRIAL REGISTRATION NUMBER: ISRCTN:
      ISRCTN52126764.

PMID- 22141571
TI  - Blockade of interleukin-17A protects against coxsackievirus B3-induced
      myocarditis by increasing COX-2/PGE2 production in the heart.
AB  - The Th17/interleukin (IL)-17 axis controls inflammation and might be important in
      the pathogenesis of experimental autoimmune myocarditis (EAM) and other
      autoimmune diseases. However, the mechanism underlying the increased Th17 cell
      response in coxsackievirus-induced myocarditis remains unclear. This study aimed
      to elucidate the regulatory mechanisms affected by blocking IL-17A responses in
      acute virus-induced myocarditis (AVMC) mice. The results showed that IL-17A and
      COX-2 proteins were significantly increased in the cardiac tissue of acute
      myocarditis, as were Th17 cells in the spleen. Using anti-mouse IL-17Ab to block
      IL-17A on day 7 of the viral myocarditis led to decreased expressions of cardiac
      tumor-necrosis factor alpha, IL-17A and transforming growth factor beta in AVMC
      mice compared to isotype control mice. COX-2 and prostaglandin E2 proteins were
      dramatically elevated, followed by marked reductions in CVB3 replication and
      myocardial injury. These results hint that the Th17/IL-17 axis is intimately
      associated with viral replication in acute myocarditis via induction of COX-2 and
      prostaglandin E2.

PMID- 22141572
TI  - Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G
      polymorphism in coronary artery disease patients with diabetes type 2 and the
      metabolic syndrome: an observational study.
AB  - BACKGROUND: Increased IL-18 serum levels have been associated with diabetes type
      2, metabolic syndrome and the severity of atherosclerosis. The present study
      investigated the presence and influence of IL-18 genetic variants on gene- and
      protein expression in stable coronary artery disease (CAD) patients. METHODS: The
      +183 A/G (rs 5744292), -137 G/C (rs 187238) and -607 C/A (rs 1946518)
      polymorphisms were determined in 1001 patients with angiographically verified
      stable CAD, and in 204 healthy controls. IL-18 gene-expression was measured in
      circulating leukocytes in 240 randomly selected patients. Circulating IL-18 and
      IL-18 binding protein levels were measured immunologically in all patients.
      RESULTS: The +183 G-allele associated significantly with lower serum levels of IL
      18 (p = 0.002, adjusted for age, glucose, body mass index and gender) and a 1.13-
      fold higher IL-18 gene-expression (p = 0.010). No influence was observed for the 
      137 G/C and -607 C/A polymorphisms. The IL-18 binding protein levels were not
      influenced by IL-18 genotypes. IL-18 levels were significantly higher in men as
      compared to women, and in patients with diabetes type 2 and metabolic syndrome
      compared to those without (p <= 0.001, all). The reduction in IL-18 levels
      according to the +183 G-allele was 3-4 fold more pronounced in diabetes and
      metabolic syndrome as compared to unaffected patients.Finally, the +183 AA
      genotype was more frequent in patients with hypertension (p = 0.042, adjusted for
      age, body mass index and gender). CONCLUSION: The reduction in serum IL-18 levels
      across increasing numbers of +183 G-alleles was especially apparent in patient
      with diabetes type 2 and metabolic syndrome, suggesting a beneficial GG genotype
      in relation to cardiovascular outcome in these patients. CLINICAL TRIAL
      REGISTRATION NUMBER: ClinicalTrials.gov: NCT00222261.

PMID- 22141573
TI  - Did AIM-HIGH aim too low?

PMID- 22141575
TI  - Are thrombophilia more multifactorial than we thought: report of mosaicism for
      FII G20210A and novel FII T20061C gene variants.

PMID- 22141576
TI  - Human hair follicle dermal cells and skin fibroblasts show differential
      activation of NF-kappaB in response to pro-inflammatory challenge.
AB  - The underlying mechanism of immune privilege in hair follicle cell dermal papilla
      (DP) and sheath (DS) populations is not well understood, and the responsiveness
      of hair follicle dermal cells to pro-inflammatory challenge presently remains
      unknown. In this work, we describe acute NF-kappaB activation in human DS, DP and
      dermal fibroblast (DF) cells challenged with TNF-alpha and IL1-beta. In contrast,
      the DS and DP cells revealed an unexpected tolerance to bacterial LPS challenge
      relative to DF cells. Understanding follicle cell responses to typical pro
      inflammatory stimuli is critical for diseases where collapse of hair follicle
      immune privilege is observed, and to further applications in autologous stem
      cell/wound healing therapeutics.

PMID- 22141577
TI  - Stamp transferred suspended graphene mechanical resonators for radio frequency
      electrical readout.
AB  - We present a simple micromanipulation technique to transfer suspended graphene
      flakes onto any substrate and to assemble them with small localized gates into
      mechanical resonators. The mechanical motion of the graphene is detected using an
      electrical, radio frequency (RF) reflection readout scheme where the time-varying
      graphene capacitor reflects a RF carrier at f = 5-6 GHz producing modulation
      sidebands at f +/- f(m). A mechanical resonance frequency up to f(m) = 178 MHz is
      demonstrated. We find both hardening/softening Duffing effects on different
      samples and obtain a critical amplitude of ~40 pm for the onset of nonlinearity
      in graphene mechanical resonators. Measurements of the quality factor of the
      mechanical resonance as a function of dc bias voltage V(dc) indicates that
      dissipation due to motion-induced displacement currents in graphene electrode is
      important at high frequencies and large V(dc).

PMID- 22141574
TI  - Emerging technologies for making glycan-defined glycoproteins.
AB  - Protein glycosylation is a common and complex posttranslational modification of
      proteins, which expands functional diversity while boosting structural
      heterogeneity. Glycoproteins, the end products of such a modification, are
      typically produced as mixtures of glycoforms possessing the same polypeptide
      backbone but differing in the site of glycosylation and/or in the structures of
      pendant glycans, from which single glycoforms are difficult to isolate. The
      urgent need for glycan-defined glycoproteins in both detailed structure-function
      relationship studies and therapeutic applications has stimulated an extensive
      interest in developing various methods for manipulating protein glycosylation.
      This review highlights emerging technologies that hold great promise in making a
      variety of glycan-defined glycoproteins, with a particular emphasis in the
      following three areas: specific glycoengineering of host biosynthetic pathways,
      in vitro chemoenzymatic glycosylation remodeling, and chemoselective and site
      specific glycosylation of proteins.

PMID- 22141578
TI  - The use of alprazolam by people who inject drugs in Melbourne, Australia.
AB  - INTRODUCTION AND AIMS: In Australia, people who inject drugs (PWID) commonly
      report the use of benzodiazepines (BZDs). This paper explores the emerging use of
      alprazolam among PWID in Melbourne, Australia. DESIGN AND METHODS: This study
      reports on 3 years of data collected through the Victorian Illicit Drug Reporting
      System (2008-2010). Structured interviews were conducted with 451 PWID and
      analysed using odds ratios and chi(2)-tests for trends over time. RESULTS: While
      the proportion of PWID reporting recent BZD use remained stable over time, the
      proportion reporting alprazolam to be their most commonly used BZD fluctuated,
      peaking in 2009. Alprazolam users were significantly more likely to report using
      illicit BZDs and to report recent BZD injection compared with users of other
      BZDs. Alprazolam use was associated with the sale of drugs for cash, but not with
      other criminal activities. DISCUSSION AND CONCLUSION: The fluctuations in
      alprazolam use over time may be reflective of medical practitioners ceasing to
      prescribe alprazolam in response to reports of associated harms; however, this
      may in turn be driving the illicit alprazolam market. While the data do not
      indicate a clear association between alprazolam use and harms, considering the
      potential severity of associated harms and the association between alprazolam use
      and anterograde amnesia, patterns of alprazolam use among PWID should be closely
      monitored. Potential changes to prescribing practice should consider unintended
      consequences, such as replacement with other BZD types, or illicitly obtained
      BZDs.

PMID- 22141579
TI  - FTO gene is related to obesity in Chilean Amerindian children and impairs HOMA-IR
      in prepubertal girls.
AB  - OBJECTIVE: The objective of this study was to investigate the allelic frequency
      of the fat mass and obesity-associated (FTO) gene (rs9939609) and its influences
      on obesity and metabolic risk biomarkers in a cohort of normal weight and obese
      Chilean children determining its ethnicity. METHODS: A total of 136 normal weight
      children and 238 obese children (between 6 and 11 yr old) from an urban setting
      were recruited for this case-control study. The children were classified as
      normal weight [body mass index (BMI) >= 5th and < 85th percentiles] or obese (BMI
      >95th percentile), according to the international age- and gender-specific
      percentiles defined by the Center for Disease Control and Prevention. The
      analysis of serum markers was carried out using commercial kits. The FTO
      polymorphism was determined through a high-resolution melting enabled real time
      polymerase chain reaction. Ethnicity was determined by analyzing mitochondrial
      DNA by the restriction fragment length polymorphism method. RESULTS: As much as
      85% of the cohort was Amerindian. The minor A allele of rs9939609 was associated
      with obesity (odds ratio (OR): 1.422 [95% confidence interval (CI) 1.068-1.868] p
      = 0.015), calculated using an additive model. In sex-stratified analysis we found
      that the risk variant (A) of rs9939609 was associated with a higher homeostasis
      model of assessment for insulin (HOMA-IR) in prepubertal obese girls. In male
      carriers of the A allele, HOMA-IR showed no further deterioration than that
      already associated with obesity. CONCLUSIONS: In summary, we confirm the
      association of the FTO gene single-nucleotide polymorphism rs9939609 with obesity
      in Chilean Amerindian children. Furthermore we show an association between the
      risk allele (A) and insulin resistance-related markers in prepubertal obese
      girls.

PMID- 22141580
TI  - Natural polyphenols in cancer therapy.
AB  - Natural polyphenols are secondary metabolites of plants involved in defense
      against different types of stress. Extracts containing these compounds have been
      used for thousands of years in traditional eastern medicine. Polyphenols act on
      multiple targets in pathways and mechanisms related to carcinogenesis, tumor cell
      proliferation and death, inflammation, metastatic spread, angiogenesis, or drug
      and radiation resistance. Nevertheless, reported effects claimed for polyphenols
      are controversial, since correlations between in vitro effects and in vivo
      evidence are poorly established. The main discrepancy between health claims
      versus clinical observations is the frequent use of nonphysiologically relevant
      concentrations of these compounds and their metabolites in efficacy and
      mechanistic studies. The present review will discuss how in vivo administration
      correlates with polyphenol metabolism, toxicity, and bioavailability. Analysis of
      the general application of polyphenols in cancer therapy will be complemented by
      potential applications in the therapy of specific tumors, including melanoma,
      colorectal and lung cancers. Possible pharmaceutical formulations, structural
      modifications, combinations, and delivery systems aimed to increase
      bioavailability and/or biological effects will be discussed. Final remarks will
      include recommendations for future research and developments.

PMID- 22141582
TI  - Articular cartilage glycosaminoglycans inhibit the adhesion of endothelial cells.
AB  - Articular cartilage undergoes severe loss of proteoglycan and its constituent
      glycosaminoglycans (GAGs) in osteoarthritis. We hypothesize that the low GAG
      content of osteoarthritic cartilage renders the tissue susceptible to
      pathological vascularization. This was investigated using an in vitro
      angiogenesis model assessing endothelial cell adhesion to GAG-depleted cartilage
      explants. Bovine cartilage explants were treated with hyaluronidase to deplete
      GAG content and then seeded with fluorescently tagged human endothelial cells
      (HMEC-1). HMEC-1 adherence was assessed after 4 hr and 7 days. The effect of
      hyaluronidase treatment on GAG content, chondrocyte viability, and biochemical
      composition of the extracellular matrix was also determined. Hyaluronidase
      treatment reduced the GAG content of cartilage explants by 78 +/- 3% compared
      with that of controls (p < 0.0001). GAG depletion was associated with
      significantly more HMEC-1 adherence on both the surface (superficial zone) and
      the underside (deep zone) of the explants (both p < 0.0001). The latter provided
      a more favorable environment for extended culture of HMEC-1 compared with the
      articulating surface. Hyaluronidase treatment altered the immunostaining for
      chondroitin sulfate epitopes, but not for lubricin. Our results support the
      hypothesis that articular cartilage GAGs are antiadhesive to endothelial cells
      and suggest that chondroitin sulfate and/or hyaluronan are responsible. The loss
      of these GAGs in osteoarthritis may allow osteochondral angiogenesis resulting in
      disease progression.

PMID- 22141584
TI  - Performance score variation between days at Australian national and Olympic
      women's artistic gymnastics competition.
AB  - We determined the inter-day variability in elite-standard women's artistic
      gymnastics competition scores. National (50 gymnasts for up to three days) and
      Olympic (24 gymnasts for up to five days) competition scores published in the
      public domain ('Giant poster pull-out', 2010 ; Gymnastics Australia, 2008 ) were
      evaluated using three statistical measures. Analyses of the inter-day differences
      in the mean scores as a percentage (MDiff%), coefficient of variation percentages
      for the mean score across both days (CV%), and Pearson correlation coefficients
      for the inter-day score (r) were interpreted using thresholds from trivial to
      large. National-class gymnasts' two-day performance variation was trivial for
      vault, small for floor and beam, and moderate for bars. When senior gymnasts
      competed for a third day the performance variation increased to moderate for
      vault. Across five days of Olympic competition there were trivial (e.g. CV%:
      vault = 0.8) to small (e.g. CV%: bars = 2.0) variations in performances between
      days on all apparatus. Olympians' performance score consistency is superior to
      senior, national-class competitors. The performance score consistency required
      for gymnasts who aspire to participate at the Olympics as a top-24 competitor is
      better than 3%.

PMID- 22141583
TI  - Phospho-ibuprofen (MDC-917) incorporated in nanocarriers: anti-cancer activity in
      vitro and in vivo.
AB  - BACKGROUND AND PURPOSE: Phospho-ibuprofen (P-I; MDC-917) inhibits the growth of
      colon cancer in mice. Here, we investigated the use of nanocarriers to improve
      its pharmacokinetics (PKs) and anti tumour efficacy. EXPERIMENTAL APPROACH: The
      cellular uptake and cytotoxicity of P-I encapsulated into liposomes and micelles,
      and its in vitro metabolic stability, were determined in cultures of human colon
      adenocarcinoma cells. The performance of liposomal P-I was further evaluated in
      PK studies in mice, and in a model of colon cancer xenografts in nude mice. KEY
      RESULTS: Liposomal P-I and micellar P-I showed significantly enhanced cellular
      uptake in the colon cancer cells. Liposomal P-I also demonstrated increased
      cytotoxicity in vitro. Free P-I was metabolized rapidly to ibuprofen in the
      presence of purified esterases. In contrast, liposomal P-I, and to a lesser
      extent micellar P-I, was resistant to esterase-mediated hydrolysis. In mice,
      liposomal P-I partially protected P-I from hydrolysis in the circulation, and
      improved the biodistribution of intact P-I and its metabolites compared to free P
      I. Liposomal P-I was more effective at inhibiting the growth of human colon
      cancer xenografts in mice, which may be explained on the basis of its improved PK
      profile compared to free P-I. CONCLUSIONS AND IMPLICATIONS: Liposome
      encapsulation of P-I partially protected P-I from esterase-mediated hydrolysis in
      mice, enhanced the cytotoxicity and bioavailability of P-I and increased its
      efficacy at inhibiting the growth of human colon cancer xenografts. These results
      indicate that liposomes are suitable nanocarriers for the delivery of P-I, and
      that the anti-tumour potential of liposomal P-I merits further evaluation.

PMID- 22141585
TI  - Movement control in older adults: does old age mean middle of the road?
AB  - Old age is associated with poorer movement skill, as indexed by reduced speed and
      accuracy. Nevertheless, reductions in speed and accuracy can also reflect
      compensation as well as deficit. We used a manual tracing and a driving task to
      identify generalized spatial and temporal compensations and deficits associated
      with old age. In Experiment 1, participants used a hand-held stylus to trace a
      path. In Experiment 2, participants steered along paths in a virtual reality
      driving simulator. In both experiments, participants were required to stay within
      the boundaries while we manipulated task difficulty by changing path width or
      movement speed. The older group showed worse performance in the highly
      constrained conditions. Corner cutting effectively reduces the curvature of bends
      but yields a greater risk of error (i.e., clipping the path or road edge). Corner
      cutting is thus less risky on wider paths, and we found that corner cutting
      increased for both age groups in both tasks when paths were wider. Crucially, we
      observed a greater degree of corner cutting in the young group compared with the
      old, suggesting the old group compensated for decreased motor skill with "middle
      of-the-road" behavior. Enforcing increased speed caused all participants to
      increase corner cutting. Thus, older participants showed spatial compensation for
      decreased skill by biasing their position toward the middle of the path in both a
      manual and steering task. External constraints (narrow paths and fast speeds)
      prevented this strategy and revealed age-related declines in skills central to
      manual control and driving.

PMID- 22141586
TI  - Referential coding contributes to the horizontal SMARC effect.
AB  - The present study tested whether coding of tone pitch relative to a referent
      contributes to the correspondence effect between the pitch height of an auditory
      stimulus and the location of a lateralized response. When left-right responses
      are mapped to high or low pitch tones, performance is better with the high
      right/low-left mapping than with the opposite mapping, a phenomenon called the
      horizontal SMARC effect. However, when pitch height is task irrelevant, the
      horizontal SMARC effect occurs only for musicians. In Experiment 1, nonmusicians
      performed a pitch discrimination task, and the SMARC effect was evident
      regardless of whether a referent tone was presented. However, in Experiment 2,
      for a timbre-judgment task, nonmusicians showed a SMARC effect only when a
      referent tone was presented, whereas musicians showed a SMARC effect that did not
      interact with presence/absence of the referent. Dependence of the SMARC effect
      for nonmusicians on a reference tone was replicated in Experiment 3, in which
      judgments of the color of a visual stimulus were made in the presence of a
      concurrent high- or low-pitched pure tone. These results suggest that referential
      coding of pitch height is a key determinant for the horizontal SMARC effect when
      pitch height is irrelevant to the task.

PMID- 22141587
TI  - Grouping illumination frameworks.
AB  - According to Koffka (1935), the lightness of a target surface is determined by
      the relationship between the target and the illumination frame of reference to
      which it belongs. However, each scene contains numerous illumination frames, and
      judging each one separately would lead to an enormous amount of computing.
      Grouping those frames that are in the same illumination would simplify the
      computation. We report a series of experiments demonstrating that nonadjacent
      regions of the visual field under the same illumination level are perceptually
      grouped together and function, to some extent, as a single framework. A small
      coplanar group of patches under its own illumination exhibits compression of
      perceived range of gray shades. We obtained the reduction in compression in the
      presence of an identically illuminated 25-patch Mondrian tableau mounted nearby
      the coplanar group. The influence of the Mondrian display was reduced when it was
      (a) moved laterally away from the test display, (b) moved farther back in depth
      from the test display, or (c) rotated to a different orientation.

PMID- 22141588
TI  - Complementary learning systems.
AB  - This paper reviews the fate of the central ideas behind the complementary
      learning systems (CLS) framework as originally articulated in McClelland,
      McNaughton, and O'Reilly (1995). This framework explains why the brain requires
      two differentially specialized learning and memory systems, and it nicely
      specifies their central properties (i.e., the hippocampus as a sparse, pattern
      separated system for rapidly learning episodic memories, and the neocortex as a
      distributed, overlapping system for gradually integrating across episodes to
      extract latent semantic structure). We review the application of the CLS
      framework to a range of important topics, including the following: the basic
      neural processes of hippocampal memory encoding and recall, conjunctive encoding,
      human recognition memory, consolidation of initial hippocampal learning in
      cortex, dynamic modulation of encoding versus recall, and the synergistic
      interactions between hippocampus and neocortex. Overall, the CLS framework
      remains a vital theoretical force in the field, with the empirical data over the
      past 15 years generally confirming its key principles.

PMID- 22141589
TI  - Alcohol-related effects on automaticity due to experimentally manipulated
      conditioning.
AB  - BACKGROUND: The use of alcohol is associated with various forms of automatic
      processing, such as approach tendencies and attentional biases, which may play a
      role in addictive behavior. The development of such automaticity has generally
      occurred well before subjects perform tasks designed to detect them. Although it
      seems plausible that this development involves some form of alcohol-related
      conditioning, this process is not usually included in the experimental procedure.
      METHODS: The development of automaticity involving alcoholic or nonalcoholic
      stimuli was experimentally manipulated via a conditioning task. Subjects were
      presented with pairs of stimuli from a set of 4 stimuli: 2 pictures of alcoholic
      beverages, and 2 pictures of nonalcoholic beverages. One of the alcoholic and 1
      of the nonalcoholic beverages was associated with reward, the other stimuli with
      punishment. Subjects had to learn to select the rewarded stimuli from pairs of 1
      rewarded and 1 punished stimulus. The task, thus experimentally established
      reward versus punishment stimulus-response-outcome associations, for alcoholic
      and for nonalcoholic stimuli. Subsequently, a cued reversal task was used to test
      automaticity involving alcoholic versus nonalcoholic, and rewarded versus
      punished stimuli. RESULTS: An association was found between heavier drinking and
      an alcohol-related conditioning bias: heavier drinkers had more difficulty
      overcoming a conditioned response when it involved selecting a previously
      punished nonalcoholic stimulus over a previously rewarded alcoholic stimulus.
      CONCLUSIONS: The study provided novel information on secondary reinforcement
      involving alcoholic stimuli: heavier drinkers may more easily develop
      automaticity related to alcohol-reward contingencies. This may have implications
      for interventions and the interpretation of findings concerning alcohol-related
      automatic processing.

PMID- 22141590
TI  - An exploratory study to determine the association between assessed facial skin
      aging and plasma isoprostane levels in middle-aged Japanese women.
AB  - BACKGROUND: One of the central mechanisms of aging is hypothesized to be
      oxidative stress. Quantification of oxidative stress in human organ systems has
      been difficult. One of the best methods is using plasma isoprostane levels, which
      have been shown to reflect oxidative stress in multiple nondermatologic organ
      systems. OBJECTIVE: To determine whether severity of aging of human skin is
      associated with plasma isoprostane levels, specifically prostaglandin F2a (PGF2a)
      and 8-iso-PGF2a while controlling for covariates such as body mass index,
      ultraviolet light exposure, diet, medication, supplement use, and stress levels.
      METHODS AND MATERIALS: Facial skin aging assessments performed by four blinded
      dermatologists were correlated with plasma isoprostane levels in 46 healthy,
      nonsmoking Japanese women aged 45 to 60. RESULTS: Individuals whose assessed skin
      age exceeded chronological age had mean plasma isoprostane levels of PGF2a and 8
      iso-PGF2a that were higher than those whose skin age was assessed to be less than
      chronological age (p = .001 and .001, respectively). These results remained
      statistically significant when adjusted for confounding variables (8-iso-PGF2a, p
      = .02; PGF2a, p = .03). CONCLUSIONS: Plasma isoprostanes as markers of
      accelerated aging of the skin merit further study.

PMID- 22141591
TI  - Pain in neonatal intensive care: role of melatonin as an analgesic antioxidant.
AB  - Endotracheal intubation is a common painful procedure in newborn care. Neonates
      are more sensitive to pain than older infants, children, and adults, and this
      hypersensitivity is further exacerbated in preterm neonates. The aim of this
      study was to evaluate the analgesic activity of melatonin during endotracheal
      intubation of the newborn by using the Neonatal Infant Pain Scale (NIPS) and
      Premature Infant Pain Profile (PIPP) score. Secondary outcome was an evaluation
      of melatonin as inflammatory responses. This was performed by measuring the
      levels of pro- and anti-inflammatory cytokines implicated in the pain. Sixty
      preterm infants were enrolled in the study and were randomly divided into two
      groups: 30 infants treated with melatonin plus common sedation and analgesia
      recommended by Italian Society of Neonatology (group 1) and 30 infants treated
      with only common sedation and analgesia. The sedative and analgesic drugs
      included atropine, fentanyl, and vecuronium. The reduction in pain score (NIPS)
      was similar in both groups at an early phase, while it (PIPP score) was lower in
      melatonin-treated group infants than the other newborns at a late phase, during
      intubation and mechanical ventilation. The differences were statistically
      significant at 12, 24, 48, and 72 hr (P < 0.001). Pro-inflammatory and anti
      inflammatory cytokines (IL-6, IL-8, IL-10 and IL-12) were higher in the common
      sedation and analgesia group than in melatonin-treated infants at 24, 48, 72 hr
      and 7 days (P < 0.001). This study suggests the use of melatonin as an adjunct
      analgesic therapy during procedural pain, especially when an inflammatory
      component is involved.

PMID- 22141592
TI  - Unexpected stereocontrolled access to 1alpha,1'beta-disaccharides from methyl 1,2
      ortho esters.
AB  - Mannopyranose-derived methyl 1,2-orthoacetates (R = Me) and 1,2-orthobenzoates (R
      = Ph) undergo stereoselective formation of 1alpha,1'beta-disaccharides, upon
      treatment with BF(3).Et(2)O in CH(2)Cl(2), rather than the expected acid
      catalyzed reaction leading to methyl glycosides by way of a rearrangement
      glycosylation process of the liberated methanol.

PMID- 22141593
TI  - Intriguing interconnections among phase transition, magnetic moment, and valence
      disproportionation in 2H-perovskite related oxides.
AB  - In this paper we report the crystal growth, structure determination, and magnetic
      properties of the 2H-perovskite related oxides, Sr(5)Co(4)O(12) and
      Sr(6)Co(5)O(15), as well as the charge disproportionation and associated phase
      transition of Sr(5)Co(4)O(12). Sr(5)Co(4)O(12) and Sr(6)Co(5)O(15) are the (m =
      2, n = 3) and (m = 1, n = 1) members of the A(3m+3n)A'(n)B(3m+n)O(9m+6n) family,
      respectively. Sr(6)Co(5)O(15) crystallizes in the space group R32 with lattice
      parameters of a = 9.5020(10) A and c = 12.379(8) A. The structure solution shows
      that Sr(6)Co(5)O(15) is isostructural with Sr(6)Rh(5)O(15). Magnetic measurements
      do not indicate any long-range magnetic order, although the Weiss temperature of 
      248 K indicates the presence of dominant antiferromagnetic interactions.
      Sr(5)Co(4)O(12) crystallizes in the space group P-3c1 with lattice parameters of
      a = 9.4705(10) A and c = 20.063(5) A at room temperature. The single crystal
      structure solution revealed that the cobalt ions in the trigonal prismatic sites
      of Sr(5)Co(4)O(12) undergo a structural transition at ~170 K, where the cobalt
      atoms are in the center of the trigonal prisms below this temperature and move
      partially toward the faces above this temperature. This structure transition is
      accompanied by a change in the magnetic moment of the oxide and can be related to
      a valence disproportionation of the cobalt ions and a concomitant Jahn-Teller
      distortion. In addition, specific heat, Seebeck coefficient, electric
      conductivity, and magnetic measurements as well as bond valence sum calculations
      were carried out for Sr(5)Co(4)O(12). Sr(5)Co(4)O(12) exhibits strong magnetic
      anisotropy but no long-range magnetic order.

PMID- 22141594
TI  - Determination of dapsone in muscle tissue and milk using high-performance liquid
      chromatography-tandem mass spectrometry.
AB  - A precise and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method for the determination of dapsone in muscle tissue and milk has been
      developed. The sample preparation was based on extraction with organic solvent
      and automated solid-phase extraction (SPE) cleanup. At least three product ions
      were monitored for the analyte. The method was validated according to the
      European Decision 2002/657/EC. Estimated analytical limits were 0.0018 ng/g for
      CCalpha and 0.0031 ng/g for CCbeta in meat and milk. An excellent linear
      concentration range was observed for both matrices with a correlation coefficient
      better than 0.997. Recoveries were 105-117% in meat and 101-108% in milk, with
      satisfactory precision and coefficients of variance (CV) less than 8%.
      Additionally, a simplified quantification approach was successfully evaluated
      depending only on the response factor (F) without the use of calibration curve.
      The developed method provides reliable and sensitive identification and
      quantification of dapsone in meat and milk.

PMID- 22141595
TI  - What cognitive behavioral techniques do therapists report using when delivering
      cognitive behavioral therapy for the eating disorders?
AB  - OBJECTIVE: Clinicians commonly "drift" away from using proven therapeutic
      techniques. This study examined the degree to which such drift occurs among
      cognitive behavioral therapy (CBT) clinicians working with a specific clinical
      population-adults with eating disorders. METHOD: The study used a correlational
      design. The participants were 80 qualified clinicians (69 women, 11 men; mean age
      = 39.2 years, range = 23-62 years) who routinely offered what they described as
      CBT to adults with eating disorders. Each clinician detailed whether and how
      often he or she used different cognitive behavioral techniques when delivering
      CBT to such patients, and each completed the anxiety scale of the Brief Symptom
      Inventory (Derogatis, 1983). RESULTS: Implementation of specific CBT techniques
      was far lower than protocols would suggest, particularly for clinicians who were
      anxious, older, or more experienced in working with the eating disorders (p <
      .05, in all cases). The use of treatment manuals was associated with greater use
      of recommended CBT techniques (p < .05, in all cases). Cluster analysis showed
      that clinicians fell into three types-behavior, motivation, and mindfulness
      oriented. CONCLUSIONS: These findings need to be extended to other therapies and
      other disorders, but they indicate the need for stronger training and closer
      supervision if clinicians are to give patients the best chance of recovery. They
      demonstrate that clinicians' use of the label CBT is not a reliable indicator of
      the therapy that is being offered.

PMID- 22141596
TI  - Changing the dissociative character of the lowest excited state of ethanol by
      pressure.
AB  - Syntheses based on physical methods, such as pressure and light, are extremely
      attractive to prepare novel materials from pure molecular systems in condensed
      phases. The structural and electronic modifications induced by selective optical
      excitation can trigger unexpected chemical reactions by exploiting the high
      density conditions realized at high pressure. The identification of the
      microscopic mechanisms regulating this reactivity, mandatory to design synthetic
      environments appealing for practical applications, requires a careful
      characterization of both structural and electronic properties as a function of
      pressure. Here, we report a spectroscopic study, by FTIR and Raman techniques, of
      the ambient temperature photoinduced reactivity of liquid C(2)H(5)OD up to 1 GPa.
      The results have been interpreted by comparison with those relative to the fully
      hydrogenated isotopomer. The dissociation along the O-H (D) coordinate is the
      primary reactive channel, but the different reactivity of the two isotopomers
      with rising pressure highlights a dramatic pressure effect on the energy surface
      of the first electronic excited state. Dissociation along the O-H (D) coordinate
      becomes the reaction rate-limiting step due to an increase with pressure of the
      binding character along this coordinate.

PMID- 22141597
TI  - Amoebal host range, host-free survival and disinfection susceptibility of
      environmental Chlamydiae as compared to Chlamydia trachomatis.
AB  - The term 'Chlamydia-like organisms' encompasses obligate intracellular bacterial
      species phylogenetically close to Chlamydiaceae. Most are associated with free
      living amoebae, and several could be responsible for respiratory tract infections
      and abortion in human and animals. Despite increasing concern about their
      pathogenic role, the prevalence, biodiversity and ecology of Chlamydia-related
      bacteria still remain largely unknown. In this study, six members of the
      Chlamydiales were tested, including Parachlamydia acanthamoebae (two different
      strains), Protochlamydia naegleriophila, Waddlia chondrophila, Criblamydia
      sequanensis and Chlamydia trachomatis as a reference. Intracellular growth was
      tested in 11 different Acanthamoeba strains, demonstrating significant
      differences in host susceptibilities to infection depending on strains
      investigated. Survival of host-free bacteria in suspension or dried onto surfaces
      was also explored, demonstrating that Chlamydia-like organisms present better
      survival capacity than C. trachomatis. Longer survival times were observed for
      bacteria suspended in rich culture medium, with survivors being detected after 10
      weeks incubation. We also tested susceptibility of host-free Chlamydia-like
      organisms to several disinfection treatments. Each chemical biocide tested
      reduced viability of host-free Chlamydia by more than 4 logs. Conversely, all
      Chlamydia-like organisms tested resisted exposure at 55  degrees C for 10 min,
      while C. trachomatis was completely inactivated.

PMID- 22141599
TI  - Fast CT metal artefacts correction based on derivative and region-based filling.
AB  - INTRODUCTION: Metal artefacts seriously degrade the quality of the CT images.
      Blurring around the junctions between metal and non-metal regions in CT images,
      metal artefacts often prevent right diagnoses, and even lead to misdiagnoses of
      patients. The aim of the study was to devise a fast and robust method to improve
      the quality of the artefact-contaminated CT images. METHODS: The proposed
      artefact correction includes the following five steps: metal object segmentation,
      forward projection, region-based filling, adaptive scaling and final image
      reconstruction. RESULTS: The feasibility of the proposed method in correcting
      metal artefacts was validated by experiments on both simulated and clinical
      images. Experiments showed the proposed correction could lead to fast and
      effective reduction of metal artefacts in CT images. CONCLUSIONS: Compared with
      other methods, the proposed method has less computational cost and allows a
      feasible and easy implantation into current CT imaging systems.

PMID- 22141598
TI  - Single blind randomized phase III trial to investigate the benefit of a focal
      lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: The treatment results of external beam radiotherapy for intermediate
      and high risk prostate cancer patients are insufficient with five-year
      biochemical relapse rates of approximately 35%. Several randomized trials have
      shown that dose escalation to the entire prostate improves biochemical disease
      free survival. However, further dose escalation to the whole gland is limited due
      to an unacceptable high risk of acute and late toxicity. Moreover, local
      recurrences often originate at the location of the macroscopic tumor, so boosting
      the radiation dose at the macroscopic tumor within the prostate might increase
      local control. A reduction of distant metastases and improved survival can be
      expected by reducing local failure. The aim of this study is to investigate the
      benefit of an ablative microboost to the macroscopic tumor within the prostate in
      patients treated with external beam radiotherapy for prostate cancer.
      METHODS/DESIGN: The FLAME-trial (Focal Lesion Ablative Microboost in prostatE
      cancer) is a single blind randomized controlled phase III trial. We aim to
      include 566 patients (283 per treatment arm) with intermediate or high risk
      adenocarcinoma of the prostate who are scheduled for external beam radiotherapy
      using fiducial markers for position verification. With this number of patients,
      the expected increase in five-year freedom from biochemical failure rate of 10%
      can be detected with a power of 80%. Patients allocated to the standard arm
      receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in
      the experimental arm receive 77 Gy to the entire prostate and an additional
      integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The
      secondary outcome measures include treatment-related toxicity, quality of life
      and disease-specific survival. Furthermore, by localizing the recurrent tumors
      within the prostate during follow-up and correlating this with the delivered
      dose, we can obtain accurate dose-effect information for both the macroscopic
      tumor and subclinical disease in prostate cancer. The rationale, study design and
      the first 50 patients included are described. TRIAL REGISTRATION: This study is
      registered at ClinicalTrials.gov: NCT01168479.

PMID- 22141600
TI  - Feasibility of MR urography in patients with urinary diversion.
AB  - INTRODUCTION: The aims of this study were to determine the diagnostic value of MR
      urography and to compare the T2- and T1-weighted MR urography techniques in
      patients with urinary diversion. METHODS: We retrospectively reviewed 19 MR
      urograms in 14 patients (13 male and one female, 8-77 years old, mean age: 54.2)
      with urinary diversion. Magnetic resonance urography examinations were performed
      with 1.5-T MR scanners. In addition to T2- and T1-weighted MR urography
      techniques, conventional T1- and T2-weighted axial and coronal sequences were
      also obtained. Collecting systems were evaluated in five segments (right proximal
      and distal collecting system, left proximal and distal collecting system and
      conduit or reservoir). Imaging features of the urinary collecting systems were
      evaluated with T2- and T1-weighted MR urography images. The clinical, laboratory
      data and follow-up imaging findings were regarded as standard. A cross table was
      formed to determine sensitivity, specificity and accuracy of MR urography
      techniques. RESULTS: T2-weighted MR urography, T1-weighted MR urography and
      combination of these two techniques could demonstrate 89.01, 87.65 and 93.83% of
      all collecting system segments, respectively. For the detection of the pathologic
      urinary segments, sensitivity, specificity and accuracy were 100, 95.29 and 95.6%
      in T2-weighted MR urography and 100, 93.42 and 93.82% in T1-weighted MR
      urography, respectively. Sensitivity, specificity and accuracy were 100% in
      combined T2- and T1-weighted MR urography technique. CONCLUSION: Magnetic
      resonance urography is an effective imaging method for the evaluation of the
      urinary system in patients with urinary diversion. T2-weighted MR urography alone
      has high sensitivity, specificity and accuracy, does not require intravenous
      contrast medium and can be obtained in 3-5 min. However, T1-weighted MR urography
      may provide additional information in some cases.

PMID- 22141602
TI  - Imaging characteristics of extrapulmonary tuberculosis lesions on dual time point
      imaging (DTPI) of FDG PET/CT.
AB  - INTRODUCTION: This study aimed to evaluate the diagnostic value of dual time
      point imaging (DTPI) of 18F-fluorodeoxyglucose (FDG) positron emission
      tomography/CT (PET/CT) for detecting the infective lesions in patients with
      extrapulmonary tuberculosis (EPTB). METHODS: Eleven patients were consecutively
      recruited and evaluated. After the intravenous injection of 369 +/- 153 MBq of
      FDG, all patients underwent FDG PET/CT imaging at two different time points:
      early scan at 57 +/- 23 min and delayed scan at 136 +/- 42 min. The maximum
      standardized uptake values (SUVmax) were recorded for both time points (early
      scan: SUVmax1 and delayed scan: SUVmax2). RESULTS: In total, 30 lesions were
      detected. The SUVmax2 in 22 of the lesions in confirmed EPTB patients were
      significantly higher than the SUVmax1 (7.9 +/- 3.2 vs. 6.8 +/- 2.5; P = 0.001).
      The SUVmax for another eight non-EPTB lesions also showed a significant
      increasing pattern of change (6.2 +/- 2.6 vs. 6.5 +/- 2.8; P = 0.044). However,
      there was insignificant difference between the mean percentage difference of
      SUVmax (%DeltaSUVmax) of EPTB and non-EPTB lesions (P = 0.06). CONCLUSION: Our
      study demonstrates that early whole body PET/CT imaging may be sufficient for the
      detection of the EPTB lesions and DTPI of PET/CT may also not be a useful
      technique in differentiating between EPTB and non-EPTB lesions. However, our
      findings are based on a limited number of patients, and therefore, further
      investigations in larger series of patients are warranted.

PMID- 22141601
TI  - Oesophageal dilatation on high-resolution CT chest in systemic sclerosis: what
      does it signify?
AB  - OBJECTIVE: To evaluate the significance of oesophageal dilatation on high
      resolution CT (HRCT) chest in patients with systemic sclerosis. METHODS: We
      retrospectively retrieved the database of patients with systemic sclerosis seen
      at our hospital between January 2008 and January 2009. A total of 50 patients (46
      women and four men) who had HRCT chest, pulmonary function testing and
      echocardiography within 1 month were included in the study. Peak pulmonary artery
      (PA) pressures and pulmonary function testing were charted. The HRCT chest was
      interpreted by a chest radiologist. Oesophageal dilatation was defined as a
      luminal coronal diameter of >=9 mm in infra-aortic oesophagus. Extent of ground
      glass, reticulation and honeycombing was objectively scored. RESULTS: Statistical
      analysis using independent t-test showed that diffusion capacity of carbon
      monoxide was significantly lower (P = 0.042) and peak PA pressures were
      significantly higher (P = 0.045) in patients with oesophageal dilatation (n = 29)
      as compared with those without oesophageal dilatation (n = 21). The two cohorts
      had no significant difference in their total lung capacity and HRCT determined
      extent of interstitial lung disease. CONCLUSION: Patients with oesophageal
      dilatation on HRCT chest had significantly lower diffusion capacity of carbon
      monoxide and higher peak PA pressures, which suggest that these patients tend to
      have more severe pulmonary vascular disease.

PMID- 22141603
TI  - Diffusion-weighted magnetic resonance imaging of borderzone necrosis in
      paediatric tuberculous meningitis.
AB  - PURPOSE: Tuberculous meningitis (TBM) is associated with borderzone necrosis
      (BZN) of the brain parenchyma in areas adjacent to meningeal inflammation.
      Diffusion-weighted MRI (DWI) allows for accurate detection of cytotoxic oedema
      associated with necrosis. Detection and characterisation of BZN using DWI to
      explain its pathogenesis in TBM have not been performed previously in children.
      Our objective was to identify the prevalence and characteristics of BZN using DWI
      in children with TBM and to correlate it with the presence, degree and
      distribution of basal meningeal enhancement (BE) in the absence of large-vessel
      thrombosis. METHODS: A retrospective descriptive MRI DWI study of 34 children
      with TBM was conducted. The topography of BZN was compared with the presence and
      severity of BE on specific MRI sequences. RESULTS: BZN was identified on MRI DWI
      in 50% of patients of which 82% had involvement of the temporal lobes. The
      severity and extent of BE in either middle cerebral artery cistern correlated
      with the presence of BZN (P = 0.02). BZN did not correlate with radiologically
      detectable vascular occlusion. CONCLUSION: BZN is common in TBM occurring in 50%
      of children. Detection and confirmation of cytotoxic oedema associated with BZN
      using DWI, and its clear relation to BE supports existing pathogenetic
      descriptions. The pathogenesis of BZN differs to that of topographical infarction
      on the basis of distribution as well as an absent statistical relationship
      between vascular occlusion and BZN.

PMID- 22141604
TI  - Multi-detector CT/CT angiogram assessment of acute pancreatic graft dysfunction.
AB  - Simultaneous pancreatic-kidney transplantation is the definitive treatment for
      patients with type 1 diabetes mellitus and renal failure. Pancreatic graft
      failure is an important postoperative complication and most commonly occurs as a
      result of pancreatitis, graft thrombosis or rejection. Distinguishing between
      these causes is necessary to determine timely, appropriate management and thereby
      potentially minimising graft loss. Multi-detector CT imaging may be used to
      identify the cause of pancreatic graft dysfunction when renal function is not
      markedly impaired.

PMID- 22141605
TI  - Nipple discharge in a screening programme: imaging findings with pathological
      correlation.
AB  - BreastScreen Australia provides free mammographic screening for asymptomatic
      women over the age of 40, targeting women aged 50-69. Occasionally women will
      present to screening programmes with a history of nipple discharge, which is
      uncommonly associated with significant underlying breast disease. Seventy-six
      women with a history of nipple discharge were recalled to BreastScreen Western
      Australia assessment centres from 2004 to 2008, of whom 72 were recalled
      primarily for their symptoms. Thirty-six of these patients had pathology
      investigations, including 18 nipple discharge smears, 17 fine needle aspirations,
      11 core biopsies and eight surgical biopsies or therapeutic resections. The
      biopsies found 11 intraduct papillomas and one invasive ductal carcinoma with
      ductal carcinoma in situ. Fourteen patients had imaging findings consistent with
      benign mammary duct ectasia. Our findings confirm that the presentation of nipple
      discharge in a screening programme is uncommonly associated with significant
      breast disease, and present representative cases of the radiological findings
      with pathological correlation of benign and malignant causes including mammary
      duct ectasia, intraduct papillomas, multiple papillomas, invasive ductal
      carcinoma and ductal carcinoma in situ.

PMID- 22141606
TI  - Distinction between postoperative recurrent glioma and delayed radiation injury
      using MR perfusion weighted imaging.
AB  - INTRODUCTION: Distinction between postoperative recurrent glioma and radiation
      injury remains a tough diagnostic problem for routine imaging methods. The
      purpose of this study is to evaluate the differentiated effectiveness of
      perfusion weighted imaging (PWI) for the two entities. METHODS: PWI was performed
      using Siemens 3.0-T MR system for 35 patients with new contrast-enhancing lesions
      at the site of treated glioma. Regions of interest (ROIs) were manually drawn at
      the contrast-enhancing lesion and peri-lesion edema areas. For calculation of
      standardised relative cerebral blood volume (rCBV) ratios, the same size ROIs
      were drawn at the area of contralateral hemisphere normal white matter on rCBV
      maps. At least five ROIs were selected at each lesion. The rCBV values were
      measured and the rCBV ratios were calculated. The maximum rCBV (rCBV(max)) ratio
      at each region was chosen for analysis. The patients were divided into two
      groups: tumour recurrence and radiation injury. The mean rCBV(max) ratios were
      compared between the two groups. RESULTS: The mean rCBV(max) ratio in the
      contrast-enhancing lesion was significantly higher in the tumour recurrence (4.36
      +/- 1.98) compared with that (1.28 +/- 0.64) in the radiation injury (P < 0.01).
      The mean rCBV(max) ratio in the peri-lesion edema was also significantly higher
      in the tumour recurrence (1.79 +/- 0.51) compared with that (0.85 +/- 0.28) in
      the radiation injury (P < 0.05). A recurrent tumour was suggested when the
      rCBV(max) ratio >2.15 based on the receiver operating characteristic curve. Four
      patients with recurrent tumour and three with radiation injury were
      misclassified. CONCLUSION: PWI is a useful method to distinguish tumour
      recurrence and radiation injury.

PMID- 22141607
TI  - Dosimetric evaluation of conventional radiotherapy, 3-D conformal radiotherapy
      and direct machine parameter optimisation intensity-modulated radiotherapy for
      breast cancer after conservative surgery.
AB  - INTRODUCTION: The use of conservative surgery combined with whole-breast
      irradiation (WBI) has been established as a valid alternative to mastectomy for
      the management of early-stage breast cancer. The aim of this study was to compare
      dosimetric parameters of the planning target volume(PTV) and organs at risk
      (OARs) between conventional radiation therapy (CR), 3-D conformal radiation
      therapy (3DCRT), and direct machine parameter optimisation intensity-modulated
      radiation therapy (DMPO-IMRT) after breast-conserving surgery. METHODS AND
      MATERIALS: Computed tomography (CT) scans from 20 patients (13 left-sided and 7
      right-sided) previously treated with T1N0 or ductal carcinoma were selected for
      this dosimetric planning study. We designed CR, 3DCRT and DMPO-IMRT plans for
      each patient. The prescribed dose was 50 Gy/2 Gy/25 f, 95% of PTV received the
      prescription dose. Doses were computed with a commercially available treatment
      planning system using convolution/superimposition (CS) algorithm. Plans were
      compared according to dose-volume histogram (DVH) analysis in terms of PTV
      homogeneity and conformity indices (HI and CI) as well as OARs dose and volume
      parameters. RESULTS: Both the HI and CI of the PTV showed statistically
      significant difference between CR, 3DCRT and DMPO-IMRT with those of DMPO-IMRT
      were best (P < 0.05). Compared with CR, 3DCRT showed smaller exposed volumes of
      ipsilateral lung, contralateral breast and heart while DMPO-IMRT indicated larger
      exposed volumes of ipsilateral lung (except for V20 and V30), contralateral
      breast and heart. In addition, DMPO-IMRT demonstrated an increase of exposed
      volume of ipsilateral lung (except for V30), contralateral breast and heart
      compared with 3DCRT. CONCLUSIONS: In WBI of breast cancer after conservative
      surgery, 3DCRT and DMPO-IMRT improved the homogeneity and conformity of the PTV
      compared with CR. Meanwhile, 3DCRT reduced the irradiated volumes of OARs at all
      dose levels listed in our study while DMPO-IMRT reduced the irradiated volumes of
      OARs in high-dose areas but increased the irradiated volumes of OARs in low-dose
      areas.

PMID- 22141608
TI  - Early post-treatment pseudo-progression amongst glioblastoma multiforme patients
      treated with radiotherapy and temozolomide: a retrospective analysis.
AB  - INTRODUCTION: To evaluate the incidence and impact of early post-chemoradiation
      (cRT) 'pseudoprogression' (PsPD) amongst glioblastoma multiforme (GBM) patients
      treated with the current standard of care - 60 Gy conformal radiotherapy with
      concurrent low-dose temozolomide, followed by six cycles of high-dose
      temozolomide (the 'Stupp protocol'). METHODS: Clinical notes and radiology
      reports for GBM patients treated as per the Stupp protocol were reviewed. PsPD
      was defined as apparent radiological progression on the first post-cRT scan, with
      further imaging within 3 months being stable or improving, while true early
      progression (ePD) was confirmed by continued progression in the subsequent 3
      months following the first post-cRT scan. RESULTS: Of the 68 patients evaluated,
      14 (21%) and 27 (40%) experienced PsPD and ePD, respectively; 3/14 (21%) patients
      experiencing PsPD and 14/27(52%), ePD were symptomatic for progression on first
      post-cRT follow-up (P = 0.096 for difference). Median survival for patients with
      ePD, PsPD and neither were 10.4, 27.4 and 13.0 months, respectively (P = 0.003
      for ePD vs. PsPD, P = 0.19 for neither vs. PsPD groups). CONCLUSION: These data
      confirm a significant incidence of PsPD in post-cRT GBM patients, associated with
      improved median survival compared with those with neither ePD nor PsPD (not
      statistically significant). It appears likely that PsPD actually represents
      tumour response, conflicting with the traditional notion that increase in lesion
      size on contrast-enhanced imaging represents disease progression. Early post-cRT
      imaging should thus be interpreted with caution. Accompanying clinical symptoms
      are more commonly associated with ePD, but do not reliably distinguish PsPD from
      ePD.

PMID- 22141609
TI  - Dose comparisons for conformal, IMRT and VMAT prostate plans.
AB  - PURPOSE: Volumetric-modulated arc therapy (VMAT) is a relatively new treatment
      technique in radiation therapy. A comparison study of conformal, intensity
      modulated radiation therapy (IMRT) and single- and double-arc VMAT plans was
      undertaken to evaluate the dosimetric impact of this new technology in prostate
      cases. The research questions were as follows: how does VMAT dosimetry compare
      with IMRT and conformal plans?; does VMAT increase the volume of bowel receiving
      lower doses?; are one or two VMAT arcs required for standard prostate cases?
      METHODS: Eight prostate cancer and post-prostatectomy patients were randomly
      selected for this study. Conformal, IMRT and single and double Arc VMAT plans
      were generated and dosimetric evaluations were performed. Each plan was
      prescribed a total of 75.6 Gy over a course of 42 fractions to the planning
      target volume (PTV). RESULTS: The Healthy Tissue Conformity Index and the
      conformation number results revealed the IMRT and two VMAT techniques to have
      superior dosimetry to the PTV compared with the conformal plans. The maximum dose
      delivered to the PTV was significantly higher with the single-arc VMAT technique
      compared with the conformal or double-arc VMAT plans. There were no significant
      differences between the planning techniques for the bladder and small bowel
      dosimetry. However, IMRT and VMAT plans delivered less radiation to the rectum
      and femoral heads, and a single-arc VMAT plan was optimal for the right femoral
      head and the two VMAT techniques were optimal to the IMRT plans for the left
      femoral head. CONCLUSIONS: Single- and double-arc VMAT consistently resulted in
      favourable or slightly superior dosimetry when compared with static gantry IMRT
      for prostate cases. Both the VMAT techniques and static gantry IMRT resulted in
      superior critical tissue sparing when compared with conformal plans.

PMID- 22141611
TI  - The use of On-Board Imaging to plan and deliver palliative radiotherapy in a
      single cohesive patient appointment.
AB  - To develop and assess a method of palliative radiotherapy utilising a kilovoltage
      imaging system incorporated with a linear accelerator. The conventionally
      separate procedures of simulation, planning and treatment were merged into a
      single appointment on a linear accelerator. The process was tested using a
      humanoid phantom and hypothetical treatment scenarios. A clinical investigation
      was then undertaken for patients requiring palliative radiotherapy. A total of 10
      treatment sites were simulated, planned and treated using the online approach.
      Each step was timed for both the phantom and patient treatments and was compared
      with a simulation process involving a separate appointment on a conventional
      simulator. The contrast and resolution achievable with the linear accelerator
      based imaging system was found to be comparable with a conventional simulator.
      Bony anatomy was plainly visible and suitable for target definition. The mean
      total treatment time for the humanoid phantom (n = 5) was 21.4 +/- 0.9 (standard
      error) mins. The mean total treatment time for actual patients (n = 10) was 25.7
      +/- 1.6 mins (the mean simulation, planning and treatment times were 11.0 +/- 0.5
      mins, 14.5 +/- 1.0 mins and 3.6 +/- 0.2 mins, respectively). This study
      demonstrated that palliative radiotherapy treatments can be simulated, planned
      and treated in a single cohesive patient appointment, using an online approach
      that is technically comparable with the conventional simulation method. This
      approach has the potential to expedite palliative radiotherapy service delivery
      and reduce resource burdens by minimising the number of patient appointments and
      wait times between appointments.

PMID- 22141610
TI  - Faculty of Radiation Oncology 2010 workforce survey.
AB  - INTRODUCTION: This paper outlines the key results of the Faculty of Radiation
      Oncology 2010 workforce survey and compares these results with earlier data.
      METHODS: The workforce survey was conducted in mid-2010 using a custom-designed
      17-question survey. The overall response rate was 76%. RESULTS: The majority of
      radiation oncologist respondents were male (n = 212, 71%), but the majority of
      trainee respondents were female (n = 59, 52.7%). The age range of fellows was 32
      92 years (median: 47 years; mean: 49 years) and that of trainees was 27-44 years
      (median: 31 years; mean: 31.7 years). Most radiation oncologists worked at more
      than one practice (average: two practices). The majority of radiation oncologists
      worked in the public sector (n = 169, 64.5%), with some working in 'combination'
      of public and private sectors (n = 65, 24.8%) and a minority working in the
      private sector only (n = 28, 10.7%). The hours worked per week ranged from 1 to
      85 (mean: 44 h; median: 45 h) for radiation oncologists, while for trainees the
      range was 16-90 (mean: 47 h; median: 45 h). The number of new cases seen in a
      year ranged from 1 to 1100 (mean: 275; median: 250). Most radiation oncologists
      considered themselves generalists with a preferred sub-specialty (43.3%) or
      specialists (41.9%), while a minority considered themselves as generalists
      (14.8%). CONCLUSIONS: There are a relatively large and increasing number of
      radiation oncologists and trainees compared with previous years. The excessive
      workloads evident in previous surveys appear to have diminished. However, further
      work is required on assessing the impact of ongoing feminisation and sub
      specialisation.

PMID- 22141613
TI  - Synthesis of an antiviral drug precursor from chitin using a saprophyte as a
      whole-cell catalyst.
AB  - BACKGROUND: Recent incidents, such as the SARS and influenza epidemics, have
      highlighted the need for readily available antiviral drugs. One important
      precursor currently used for the production of Relenza, an antiviral product from
      GlaxoSmithKline, is N-acetylneuraminic acid (NeuNAc). This substance has a
      considerably high market price despite efforts to develop cost-reducing
      (biotechnological) production processes. Hypocrea jecorina (Trichoderma reesei)
      is a saprophyte noted for its abundant secretion of hydrolytic enzymes and its
      potential to degrade chitin to its monomer N-acetylglucosamine (GlcNAc). Chitin
      is considered the second most abundant biomass available on earth and therefore
      an attractive raw material. RESULTS: In this study, we introduced two enzymes
      from bacterial origin into Hypocrea, which convert GlcNAc into NeuNAc via N
      acetylmannosamine. This enabled the fungus to produce NeuNAc from the cheap
      starting material chitin in liquid culture. Furthermore, we expressed the two
      recombinant enzymes as GST-fusion proteins and developed an enzyme assay for
      monitoring their enzymatic functionality. Finally, we demonstrated that Hypocrea
      does not metabolize NeuNAc and that no NeuNAc-uptake by the fungus occurs, which
      are important prerequisites for a potential production strategy. CONCLUSIONS:
      This study is a proof of concept for the possibility to engineer in a filamentous
      fungus a bacterial enzyme cascade, which is fully functional. Furthermore, it
      provides the basis for the development of a process for NeuNAc production as well
      as a general prospective design for production processes that use saprophytes as
      whole-cell catalysts.

PMID- 22141731
TI  - Rapid and efficient ultrasound-assisted method for the combinatorial synthesis of
      spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives.
AB  - An efficient one-pot synthesis of spiro[indoline-3,4'-pyrano[2,3-c]pyrazole]
      derivatives by four-component reaction of hydrazine, beta-keto ester, isatin, and
      malononitrile or ethyl cyanoacetate catalyzed by piperidine under ultrasound
      irradiation is described. This synthesis was confirmed to follow the group
      assistant-purification chemistry (GAP) chemistry process, which can avoid
      traditional chromatography and recrystallization purifications.

PMID- 22141732
TI  - Aprepitant plus palonosetron and dexamethasone for prevention of chemotherapy
      induced nausea and vomiting in patients receiving multiple-day cisplatin
      chemotherapy.
AB  - BACKGROUND: Chemotherapy-induced nausea and vomiting remain among the most feared
      adverse effects for cancer patients. AIM: The aim of this study was to evaluate
      the efficacy and safety of a combination of aprepitant, palonosetron and
      dexamethasone as antiemetic prophylaxis in patients receiving multiple-day
      cisplatin-based chemotherapy. METHODS: Forty-one solid cancer patients received
      aprepitant, palonosetron and dexamethasone during a 3-day cisplatin-based
      chemotherapy. Primary end-point was complete response in the overall phase (day 1
      until 5 days after the end of chemotherapy). RESULTS: Aprepitant in combination
      with palonosetron and dexamethasone was safe, with hiccups (31.7%), fatigue
      (17.1%), headache (14.6%) and constipation (12.2%) the most common treatment
      related adverse events, mostly mild. Complete response was seen in 58.5% of
      patients in the overall phase. In 23 patients receiving aprepitant in combination
      with palonosetron and dexamethasone more than one cycle (range: 2-5 cycles), the
      cumulative emetic protection rate after five cycles was 0.82. CONCLUSION: This
      study shows aprepitant in combination with palonosetron and dexamethasone is safe
      and effectively controls chemotherapy-induced nausea and vomiting in patients
      undergoing 3-day cisplatin-based chemotherapy, moreover, the efficacy is
      maintained during multiple cycles.

PMID- 22141733
TI  - A chikungunya outbreak associated with the vector Aedes albopictus in remote
      villages of Gabon.
AB  - Chikungunya virus (CHIKV) recently caused major urban outbreaks in central
      African countries such as the Democratic Republic of Congo (DRC), Cameroon, and
      Gabon. In Gabon, the tiger mosquito Aedes albopictus was shown to be the main
      CHIKV vector during the 2007 outbreak. This invasive Asian species was first
      identified in Gabon in early 2007, and was thought to be restricted mainly to
      coastal provinces where urban epidemic CHIKV foci were recorded. Here we report a
      CHIKV outbreak in a small cluster of villages isolated in the deep forest of
      southern Gabon, in which A. albopictus was the main vector. This observation
      indicates concomitant geographic and ecological spread of CHIKV activity and A.
      albopictus in remote environments in central Africa, as well as an enhanced risk
      of propagation of epidemic arboviruses.

PMID- 22141734
TI  - Commentary: theoretical and methodological challenges to the study of working
      memory in developmental disorders - a comment on Rhodes et al. (2012).

PMID- 22141735
TI  - The release of zinc, copper, lead, and cadmium from the mineral tissue of teeth
      under the influence of soft drinks and sour-tasting food.
AB  - This study was carried out with the aim of identifying the effects of consuming
      sour-tasting food and refreshing drinks on the bone tissue of teeth among
      teenagers. The cumulative effect of a year-long exposure of teeth to the erosive
      effects of a model system of acidic media (citric acid, lactic acid, acetic acid,
      apple vinegar, lemonade, the soft drink Sprite, mineral water) was studied. The
      effects were registered based on the amount of released biometal ions, of zinc
      and copper, and toxic lead, during a period of 24 hr at room temperature, using
      the potentiometric stripping analysis. In the given time span, amounts ranging
      from 75 to 750 ppm of zinc, from 0.1 to 1.0 ppm of copper, and up to 1.5 ppm of
      lead were released from the dental matrix, while the release of cadmium was below
      the level of detection. The changes to the mineral structure of the bone tissue
      were monitored by the Fourier's transformation infrared spectroscopy and scanning
      electron microscopy technique. These studies have shown that under the influence
      of an acidic medium significant erosion to the tooth enamel ensues and that the
      eroded surfaces had a radius of 1-5 MUm.

PMID- 22141736
TI  - Similar neurotoxicity of an alternating compared to a continuous low-dose
      schedule of thalidomide for relapsed/refractory multiple myeloma.

PMID- 22141737
TI  - Chronic intermittent ethanol exposure and its removal induce a different miRNA
      expression pattern in primary cortical neuronal cultures.
AB  - BACKGROUND: Increasing evidence indicates that repeated exposure to and
      withdrawal from alcohol can result in persistent molecular and cellular
      adaptations. One molecular adaptation that occurs is the regulation of gene
      expression, which is thought to lead to the functional alterations that
      characterize addiction: tolerance, dependence, withdrawal, craving, and relapse.
      MicroRNAs (miRNAs) have been recently identified as master regulators of gene
      expression through post-transcriptional regulation. However, the role of miRNAs
      in the neuroadaptations after alcohol removal has not yet been directly
      addressed. METHODS: We employed a chronic intermittent ethanol (CIE) model in
      primary cortical neuronal cultures to examine the global extent of differential
      miRNA expression using a TaqMan real-time PCR miRNA array. RESULTS: Sixty-two
      miRNAs were differentially expressed after 10 days of CIE (CIE10) treatment (n =
      42 with false discovery rate [FDR] < 0.05 and fold change > 2) and 5 days post
      CIE (P5) treatment (n = 26) compared with untreated control values. Compared to
      CIE10, ethanol (EtOH) removal experience in P5 induced a distinct expression
      pattern, including 20 differentially expressed miRNAs, which did not exhibit a
      significant change at CIE10. The predicted target molecules of EtOH removal
      induced miRNAs function mainly in the regulation of gene transcription, but also
      function in neuron differentiation, embryonic development, protein
      phosphorylation, and synaptic plasticity. Interestingly, some of the miRNAs
      differentially expressed 5 days after CIE treatment were found to cluster on
      chromosomes near CpG islands, suggesting that they share functional similarity by
      targeting alcohol-related genes. CONCLUSIONS: Taken together, these results
      suggest a potential role of differentially expressed miRNAs in mediating EtOH
      removal-related phenotypes.

PMID- 22141739
TI  - DNA base-specific modulation of microampere transverse edge currents through a
      metallic graphene nanoribbon with a nanopore.
AB  - We study two-terminal devices for DNA sequencing that consist of a metallic
      graphene nanoribbon with zigzag edges (ZGNR) and a nanopore in its interior
      through which the DNA molecule is translocated. Using the nonequilibrium Green
      functions combined with density functional theory, we demonstrate that each of
      the four DNA nucleobases inserted into the nanopore, whose edge carbon atoms are
      passivated by either hydrogen or nitrogen, will lead to a unique change in the
      device conductance. Unlike other recent biosensors based on transverse electronic
      transport through translocated DNA, which utilize small (of the order of pA)
      tunneling current across a nanogap or a nanopore yielding a poor signal-to-noise
      ratio, our device concept relies on the fact that in ZGNRs local current density
      is peaked around the edges so that drilling a nanopore away from the edges will
      not diminish the conductance. Inserting a nucleobase into the nanopore affects
      the charge density in the surrounding area, thereby modulating edge conduction
      currents whose magnitude is of the order of microampere at bias voltage 0.1 V.
      The proposed biosensors are not limited to ZGNRs and they could be realized with
      other nanowires supporting transverse edge currents, such as chiral GNRs or wires
      made of two-dimensional topological insulators.

PMID- 22141740
TI  - The keystone flap for lower extremity defects.

PMID- 22141738
TI  - Modulation of T cell immune functions by the prostaglandin E(2) - cAMP pathway in
      chronic inflammatory states.
AB  - Cyclic AMP is the intracellular second messenger for a variety of
      immunoregulatory inflammatory mediators such as prostaglandin E2, adenosine and
      histamine that signal to effector T cells from monocytes, macrophages and
      regulatory T cells. Protein kinase A (PKA) type I localizes to lipid rafts in
      effector T cells during T cell activation and directly modulates proximal signal
      events including phosphorylation of C-terminal Src kinase (Csk), which initiates
      a negative signal pathway that fine-tunes the T cell activation process. The PKA
      Csk immunoregulatory pathway is scaffolded by the A kinase anchoring protein
      ezrin, the Csk binding protein phosphoprotein associated with glycosphingolipid
      enriched membrane microdomains and the linker protein ezrin/radixin/moesin
      binding protein of 50 kDa. This pathway is hyperactivated in chronic infections
      with an inflammatory component such as HIV, other immunodeficiencies and around
      solid tumours as a consequence of local inflammation leading to inhibition of
      anti-tumour immunity. LINKED ARTICLES This article is part of a themed section on
      Novel cAMP Signalling Paradigms. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2012.166.issue-2.

PMID- 22141741
TI  - Total synthesis of (+)-seco-C-oleanane via stepwise controlled radical cascade
      cyclization.
AB  - An asymmetric concise total synthesis of the (+)-seco-C-oleanane 1 was
      accomplished. The successful route to this natural product involves as the key
      step a stepwise regio- and stereocontrolled catalytic radical polyene cascade
      cyclization from preoleanatetraene oxide (16), a process mediated by Cp(2)TiCl.
      The use of this single-electron-transfer complex permits mild cyclization
      conditions without using unnecessary prefunctionalizations and stops the process
      at the bicyclic level. Theoretical data revealed high activation energy for the
      third ring closure, which would account for the control of the cyclization. This
      process also led to natural (-)-achilleol B, camelliol A, and (+)-seco-beta
      amyrin as minor compounds.

PMID- 22141745
TI  - The landscape of services for drug users in Yogyakarta, Indonesia.
AB  - INTRODUCTION AND AIMS: Drug use has increased rapidly in Indonesia since the late
      1990s. The formal drug treatment sector has grown within the bounds of available
      government funding; however, there is also a substantial informal sector which
      provides a range of services for current and former users. While information
      regarding the former is available from the provincial and national governments,
      there are few sources that detail the latter. The aim of the current study,
      therefore, is to document the drug treatment services in one Indonesian city,
      Yogyakarta. DESIGN AND METHODS: This qualitative study utilised nine key
      informant interviews with drug treatment workers from nine government and non
      government treatment services. Transcripts were analysed thematically. RESULTS:
      There exists a patchwork of enthusiastic yet under-resourced non-government
      services that complement the government rehabilitation and withdrawal programs in
      Yogyakarta. The focus of most such services is on abstinence (including several
      faith-based residential rehabilitation programs); however, some harm reduction
      programs have emerged in recent years. Under-utilisation is a feature of many non
      government services, and all respondents acknowledged a significant gap in
      service coordination. DISCUSSION AND CONCLUSIONS: Yogyakarta has a drug treatment
      sector in which most major treatment types are represented, and there appears to
      be potential for growth within many organisations. Nevertheless, the number and
      reach of the services are limited by a lack of resources and collaboration, and
      there are substantial cultural barriers to improving inter-organisational
      coordination. This study suggests that Yogyakarta and greater Indonesia may
      benefit from greater service coordination facilitated by local government.

PMID- 22141746
TI  - Primacy of information about means selection over outcome selection in goal
      attribution by infants.
AB  - It has been shown that, when observing an action, infants can rely on either
      outcome selection information (i.e., actions that express a choice between
      potential outcomes) or means selection information (i.e., actions that are
      causally efficient toward the outcome) in their goal attribution. However, no
      research has investigated the relationship between these two types of information
      when they are present simultaneously. In an experiment that addressed this
      question directly, we found that when outcome selection information could
      disambiguate the goal of the action (e.g., the action is directed toward one of
      two potential targets), but means selection information could not (i.e., the
      action is not efficiently adjusted to the situational constraints), 7- and 9
      month-old infants did not attribute a goal to an observed action. This finding
      suggests that means selection information takes primacy over outcome selection
      information. The early presence of this bias sheds light on the nature of the
      notion of goal in action understanding.

PMID- 22141747
TI  - Right-left digit ratio (2D:4D) and maximal oxygen uptake.
AB  - A low digit ratio (2D:4D) and low 2D:4D in the right compared with the left hand
      (right-left 2D:4D) are thought to be determined by high in utero concentrations
      of testosterone, and are related to "masculine" traits such as aggression and
      performance in sports like running and rugby. Low right-left 2D:4D is also
      related to sensitivity to testosterone as measured by the number of cytosine
      adenine-guanine triplet repeats in exon 1 of the androgen receptor gene. Here we
      show that low right-left 2D:4D is associated with high maximal oxygen uptake
      (VO2(max)), high velocity at VO2(max), and high maximum lactate concentration in
      a sample of teenage boys. We suggest that low right-left 2D:4D is linked to
      performance in some sports because it is a proxy of high sensitivity to prenatal
      and maybe also circulating testosterone and high VO2(max).

PMID- 22141748
TI  - Interference between maintenance and processing in working memory: the effect of
      item-distractor similarity in complex span.
AB  - Four experiments examined the effect of phonological similarity between items and
      distractors on complex span performance. Item-distractor similarity benefited
      serial recall when distractors followed the items they were similar to, but not
      when distractors preceded the items they were similar to. These findings are
      predicted by C-SOB (contextual serial order in a box), a computational model of
      complex span. The model assumes that distractors are involuntarily encoded into
      memory, being associated to the preceding item's list position. Distractors
      interfere with items by superposition of distributed representations that are
      associated to the same position. Superposition distorts item memory; this
      distortion is less severe when the distractor is similar to the item. Further
      support for the assumption that distractors are encoded at the position of the
      preceding item comes from the finding that intrusions of distractors at recall
      tended to come from the position of the target item. In addition, intruding
      distractors tend to replace items to which they are similar, showing that lack of
      distinctiveness also contributes to interference.

PMID- 22141749
TI  - Microbial methane cycling in a terrestrial mud volcano in eastern Taiwan.
AB  - Microbial communities responsible for methane cycling in mud volcanoes onshore
      are poorly characterized. This study analysed bubbling fluids and cored sediments
      retrieved from a mud volcano in eastern Taiwan. The pore water profiles revealed
      that methane concentrations generally increased with depth and changed
      dramatically at different depth intervals at different sites. The methane
      concentrations were inversely correlated with Fe(2+)/Mn(2+) concentrations and
      delta(13)C values of methane, marking iron/manganese-methane transition zones in
      the sediment cores. Archaeal communities were dominated by ANME-2a members and
      methylotrophic methanogens, whereas bacterial communities consisted primarily of
      Proteobacteria, Firmicutes and Bacteroidetes. The 16S rRNA gene copy numbers of
      ANME-2a and Desulfuromonas/Pelobacter populations varied by two to three orders
      of magnitude along the profile and exhibited a pattern comparable with those of
      Fe(2+) and delta(13)C values of methane. These lines of evidence suggest a
      coupling between anaerobic methanotrophy and metal reduction in the metal-methane
      transition zones under sulfate-deficient conditions, a metabolic scheme
      contrasting with that observed in marine cold seeps. Anaerobic methanotrophs
      proliferate by removing methane produced from in situ methanogenesis and
      originating from the deep source. Methane finally emitted into the atmosphere is
      quantitatively and isotopically altered by various microbial processes
      compartmentalized at different depth intervals.

PMID- 22141750
TI  - The impact of a cancer Survivorship Care Plan on gynecological cancer patient and
      health care provider reported outcomes (ROGY Care): study protocol for a
      pragmatic cluster randomized controlled trial.
AB  - BACKGROUND: There is a need for improvement of information provision and post
      treatment care for cancer survivors. A Survivorship Care Plan (SCP) is
      recommended by the American Institute of Medicine and the Dutch Health Council,
      which is a summary of patients' course of treatment as a formal document, and
      includes recommendations for subsequent cancer surveillance, management of late
      effects, and strategies for health promotion. Until now, evidence on the effects
      of implementing the SCP in clinical practice is lacking. The rationale and study
      design of a pragmatic cluster randomized trial, aiming to assess the impact of
      SCP care in routine clinical practice, is presented. METHODS/DESIGN: A web-based
      patient registration system 'Registrationsystem Oncological GYnecology' (ROGY) is
      used by gynecologists in the South of the Netherlands since 2006. A personalized
      SCP can automatically be generated out of ROGY. In this pragmatic cluster
      randomized controlled trial, 12 hospitals are randomized to either 'usual care'
      or 'SCP care'. In patients with 'usual care', the gynecologist provides care as
      usual. In patients with 'SCP care', information about the tumor stage and
      treatment is personally discussed with the patient and a document is handed to
      the patient. Prospectively, all patients diagnosed with endometrial or ovarian
      cancer in the participating hospitals will be approached for study participation.
      Patients will complete questionnaires after surgery, and before additional
      treatment, and after 6, 12, 18 and 24 months. In addition, health care providers
      will be asked their opinion about implementation of SCP care. Primary outcome is
      defined as patient satisfaction with information provision and care. Secondary
      outcomes are illness perception, health-related quality of life, health care use,
      prevalence, course and referral rate of survivors with psychosocial distress, and
      health care providers' evaluation of SCP care. DISCUSSION: The ROGY Care trial
      will help to gain insight into the impact of SCP care on patient reported
      outcomes, and on the evaluation of cancer survivors and health care providers of
      the different elements of the SCP. Therefore, results will contribute to efforts
      to improve quality of care for cancer survivors. TRIAL REGISTRATION: Trial
      Registration: http://www.ClinicalTrials.gov. Identifier: NCT01185626 Medical
      Research Ethics Committee Reference Number: NL33429.008.10 Grant Reference
      Number: UVT2010-4743.

PMID- 22141751
TI  - Adherence to a six-dose regimen of artemether-lumefantrine among uncomplicated
      Plasmodium falciparum patients in the Tigray Region, Ethiopia.
AB  - BACKGROUND: In 2004, Ethiopia switched its first-line treatment of uncomplicated
      Plasmodium falciparum malaria from sulphadoxine-pyrimethamine to a fixed
      artemisinin-based combination therapy (ACT), artemether-lumefantrine (AL).
      Patient adherence to AL regimen is a major determining factor to achieve the
      desired therapeutic outcome. The aim of this study was to measure patient
      adherence levels to the six-dose AL regimen for the treatment of uncomplicated P.
      falciparum malaria and to identify its determinant factors in rural areas of the
      Tigray region, Ethiopia METHODS: The study was conducted under routine health
      service delivery at health posts level. Patients/caregivers were not informed
      about their home visit and were traced on the day after they finished the AL
      regimen. By combining the response to a structured questionnaire and the tablet
      count from the blister, adherence level was classified into three categories:
      definitely non-adherent, probably non-adherent and probably adherent. Reasons for
      being definitely non-adherent were also assessed. For the purpose of examine risk
      factors, definitely non-adherent and probably non-adherent was merged into a non
      adherent group. Variables found significantly associated (p < 0.05) with the
      adherence level on the univariate analysis were fitted into a multivariate
      logistic regression model. RESULTS: Out of the total initially enrolled 180
      patients, 86.1% completed the follow-up. Out of these, 38.7% were classified as
      probably adherent, 34.8% as probably non-adherent, and 26.5% were definitely non
      adherent. The most common reasons that definitely non-adherents gave for not
      taking the full dose were "too many tablets" (37.3%) and to "felt better before
      finished the treatment course" (25.5%). The adherence of the patients was
      associated with the ownership of a radio (adjusted odd ratio, AOR: 3.8; 95% CI:
      1.66-8.75), the belief that malaria can be treated traditionally (AOR: 0.09; 95%
      CI: 0.01-0.78) and a delay of more than one day in seeking treatment after the
      onset of fever (AOR: 5.39; 95% CI: 1.83-15.88). CONCLUSION: The very low
      adherence to AL found in this study raises serious concerns for the malaria
      control in the region. The implementation of a monitoring adherence system is
      essential to ensure long-term treatment efficacy.

PMID- 22141752
TI  - Performance of individual Helicobacter pylori antigens in the immunoblot-based
      detection of H. pylori infection.
AB  - To develop a specific line blot (LB) for supporting ELISA-based serodiagnosis of
      Helicobacter pylori infection, individual native/recombinant H. pylori antigens
      were evaluated with respect to their reactivity with both serum IgG and IgA from
      156 dyspeptic screening patients (67% H. pylori positive). Of 13 antigens,
      HP0175, p17, and p19 revealed highest positive likelihood ratios for H. pylori
      specific IgG (> 5.0) and were selected as LB substrates, in addition to the
      established virulence markers VacA and CagA. For validation, the LB was compared
      to a commercial whole-cell-lysate-based ELISA by parallel (re-)analysis of 156
      screening sera, 22 sera from diabetes mellitus patients and 15 sera from follow
      up patients after H. pylori eradication. In screening patients, the combined use
      of IgG ELISA and LB revealed a sensitivity, specificity, and accuracy of 94%,
      81%, and 90%, respectively, whereas IgG ELISA alone exhibited a low specificity
      of 75%. In diabetic and follow-up patients, IgA ELISA exhibited high accuracy of
      89% and 93%, respectively, whereas IgG detection was unreliable (accuracy < 80%).
      In conclusion, using HP0175, p17, p19, CagA, and VacA as LB substrates
      significantly improves the specificity of anti-H. pylori IgG analysis, providing
      a reliable tool for (1) confirmation/refutation of ELISA-based screening results
      and (2) assessment of the CagA/VacA status.

PMID- 22141753
TI  - Metamemory judgments and study time allocation in young and older adults:
      dissociative effects of a generation task.
AB  - This study explored age-related differences in the use of metacognitive judgment
      to allocate extra study time according to the perceived difficulty of a learning
      task. The task difficulty was varied by manipulating the encoding condition which
      entailed either generating or reading paired associates. Perceived difficulty was
      measured by the global prediction rating, whereby participants predicted that
      they would recall fewer words in the learning task they considered hardest.
      Participants were first asked to predict their own future recall performance and
      then learned paired associates in their own time, and finally performed a cued
      recall test for each encoding condition. Our results replicated earlier findings
      that generation improves the memory performance of both young and older adults.
      However, both groups thought that generation would be more difficult than reading
      and predicted that they would recall fewer words under that condition. The young
      adults allocated different amounts of study time to the two tasks, whereas the
      older adults allocated the same time. This was interpreted as an age-related
      impairment in self-initiated coordination of metacognitive judgment and the
      control processes required for effective allocation of study time.

PMID- 22141758
TI  - Pfizer Sandwich Laboratories: where drug metabolism first met drug discovery.

PMID- 22141756
TI  - Novel biomarkers for the detection of wound infection by wound fluid RT-PCR in
      rats.
AB  - Wound infection is a form of host damage resulting from an imbalance in pathogen
      virulence and the host immune response. However, at present, diagnosis is based
      solely on bacterial numbers or inflammatory signs and is therefore not precise.
      Thus, infection diagnosis requires indicators of both of these factors. We
      focused on wound fluid because it includes both bacteria and host cells. The
      purpose of this study was to establish biomarkers that reflect both bacterial and
      host factors using the reverse transcription-polymerase chain reaction method on
      the centrifugal precipitation of wound fluids (wound fluid RT-PCR). We created
      full thickness wounds in animal models of the three groups: control, colonization
      and infection, which were conditioned by administration of different
      concentrations of Pseudomonas aeruginosa dispersion. Messenger RNA expression in
      bacteria and host cells was analysed. Expression of bacterial housekeeping genes
      was detected in the samples in the colonization and infection groups. Expression
      of host housekeeping genes was detected in all samples from the three groups.
      Expression of toxA, encoding the virulence factor exotoxin A, was detected in 90%
      of samples in the infection group only. Expression of Foxp3, encoding the
      transcription factor forkhead box P3, was detected in 100% of samples only in the
      colonization group. These results revealed that wound fluid RT-PCR analysis
      reflected both bacterial virulence and the host immune status, and we determined
      the combination of novel biomarkers that can discriminate these three groups. We
      anticipate that wound fluid RT-PCR could be applied in the future to diagnose
      wound infection.

PMID- 22141755
TI  - Impaired neonatal macrophage phagocytosis is not explained by overproduction of
      prostaglandin E2.
AB  - BACKGROUND: Neonates and young infants manifest increased susceptibility to
      bacterial, viral and fungal lung infections. Previous work has identified a role
      for eicosanoids in mediating host defense functions of macrophages. This study
      examines the relationship between alveolar macrophage (AM) host defense and
      production of lipid mediators during the neonatal period compared to adult AMs.
      METHODS: AMs were harvested from young (day 7 and day 14) and adult (~10 week)
      rats. The functionality of these cells was assessed by examining their ability to
      phagocytose opsonized targets, produce cytokines, eicosanoids and intracellular
      cAMP measured by enzyme immunoassays, and gene expression of proteins, enzymes
      and receptors essential for eicosanoid generation and phagocytosis measured by
      real time RT-PCR. RESULTS: AMs from young animals (day 7 and 14) were defective
      in their ability to phagocytose opsonized targets and produce tumor necrosis
      factor (TNF)- alpha. In addition, young AMs produce more prostaglandin (PG) E(2),
      a suppressor of host defense, and less leukotriene (LT) B(4), a promoter of host
      defense. Young AMs express higher levels of enzymes responsible for the
      production of PGE(2) and LTB(4); however, there was no change in the expression
      of E prostanoid (EP) receptors or LT receptors. Despite the similar EP profiles,
      young AMs are more responsive to PGE(2) as evidenced by their increased
      production of the important second messenger, cyclic AMP. In addition, young AMs
      express higher levels of PDE3B and lower levels of PDE4C compared to adult AMs.
      However, even though the young AMs produced a skewed eicosanoid profile, neither
      the inhibition of PGE(2) by aspirin nor the addition of exogenous LTB(4) rescued
      the defective opsonized phagocytosis. Examination of a receptor responsible for
      mediating opsonized phagocytosis showed a significant decrease in the gene
      expression levels of the Fcgamma receptor in young (day 7) AMs compared to adult
      AMs. CONCLUSION: These results suggest that elevated production of PGE(2) and
      decreased production of LTB(4) do not contribute to impaired opsonized macrophage
      phagocytosis and highlight an important difference between young and adult AMs.

PMID- 22141879
TI  - One-pot synthesis of polypeptide-gold nanoconjugates for in vitro gene
      transfection.
AB  - We present a general strategy to create polypeptide-gold nanoconjugates by a one
      pot synthesis approach, where polypeptides act not only as capping agents but
      also as reductants for the formation of gold nanoparticles without the need of an
      additional reducing agent. The present approach is environmentally benign,
      facile, and flexible for the design of functional polypeptide-gold
      nanoconjugates. As a demonstration of as-synthesized nanoconjugates for
      biomedical applications, the resulting positively charged polypeptide-conjugated
      gold nanoparticles are applied for gene delivery. A gradual and prolonged
      intracellular uptake and transfection is achieved, and transfection activity is
      maintained for almost two weeks with no obvious cytotoxicity. The biologically
      based method presented in this work will provide a new alternative in creating a
      variety of multifunctional polypeptide-metallic nanoconjugates in a simple and
      straightforward manner, which will be more advantageous for their applications in
      biomedicine.

PMID- 22141882
TI  - Morphocytochemical, immunohistochemical and ultrastructural characterization of
      the head kidney of fat snook Centropomus parallelus.
AB  - This study characterized the structure and the morphocytochemical,
      immunohistochemical and ultrastructural aspects of the head kidney (HK) of the
      fat snook Centropomus parallelus. The HK is enclosed by a thin capsule of
      connective tissue, from which fine trabeculae originate and branch into the
      interior of organ. In the parenchyma, there are aggregates of lymphoid cells
      containing populations of lymphocytes T immunopositive for CDRO45, in a nodular
      arrangement, around blood vessels and melano-macrophage centres. Among the cells
      that constituted these aggregates and surrounded them, were macrophages and
      monocytes, and their precursors, with strong immunopositivity for CD68, along
      with cells of the granulocytic lineage in various phases of maturation positive
      for lysozyme and PAS. Macrophages and chromaffin and interrenal cells are also
      present. Ultrastructurally, the HK comprises a reticulum-endothelial stroma
      consisting of endothelial cells, reticulocytes of the fibroblast type and
      macrophage type and a parenchyma with increased cellularity, principally blood
      cells of the erythrocytic, granulocytic, lymphocytic, monocytic and thrombocytic
      series.

PMID- 22141883
TI  - New data on Lepidion schmidti (Gadiformes: Moridae) from the north-east Atlantic
      Ocean.
AB  - A new record of Lepidion schmidti (Gadiformes: Moridae) is reported from the Bay
      of Biscay (north-east Atlantic Ocean). Lepidion schmidti is a rare and poorly
      known species, scarcely described in the ichthyological literature. Morphometric
      and meristic characteristics of the specimen are given. A compilation of the
      specimens caught in the north-east Atlantic Ocean was carried out and the current
      status of the species in Atlantic waters is discussed. Lepidion schmidti is
      characterized mainly by the presence of an inverted V-shaped patch of vomerine
      teeth and a V-shaped crest on the dorsal surface of the head with the apex
      anterior. The presence of supernumerary anal fin rays in this species is
      described for the first time. The results obtained confirm the presence of L.
      schmidti from the north-east Atlantic Ocean.

PMID- 22141884
TI  - Records of anglerfishes (Lophiiformes: Lophiidae) from the western South Pacific
      Ocean, with descriptions of two new species.
AB  - Species of Lophiidae collected from the western South Pacific Ocean are examined.
      Nine nominal species are recognized, all but one species with their distributions
      extended eastwards and southwards from the western Pacific Ocean. Two new species
      are described from Polynesia. Lophiodes iwamotoi n. sp. is described from five
      specimens collected from Savannah Seamount. It is characterized by a relatively
      long third dorsal-fin spine (56.9-70.8% standard length, L(S)) that extends (when
      retracted) to between the end of the soft dorsal fin and caudal-fin base; a
      relatively short fifth dorsal-fin spine (10.5-13.1% L(S)); a relatively short and
      narrow head; 19-20 pectoral-fin rays. Lophiodes maculatus n. sp. is described
      from 20 specimens collected from Marquesas Islands. It is characterized by an
      extremely long third dorsal-fin spine (71.9-87.2% L(S)), extending well beyond
      the caudal-fin base; a relatively short fifth dorsal-fin spine (11.4-16.5% L(S));
      17-18 pectoral-fin rays. A key to the lophiids in the western South Pacific Ocean
      is provided.

PMID- 22141885
TI  - A new species of gravel-dwelling loach (Ostariophysi: Nemacheilidae) from the
      Nepalese Himalayan foothills.
AB  - Turcinoemacheilus himalaya, new species, is described from the Koshi and Gandaki
      River basins of Nepal. The new species is distinguished from its hypothesised
      congener, Turcinoemacheilus kosswigi, from the Euphrates, Tigris and Karoun
      basins of the Middle East, by the presence of small scales on the posterior half
      of its body (v. absence of all scales), its shorter caudal peduncle (caudal
      peduncle length 12-15% standard length, L(S) v. 16-23), its shorter snout (snout
      length 28-36% head length, L(H) v. 40-49) and by features of its colour pattern,
      including the presence of small irregularly shaped dark grey markings over the
      lateral body surface. Turcinoemacheilus himalaya is known to date only from
      Nepal.

PMID- 22141886
TI  - Dietary niche overlap in sympatric asexual and sexual livebearing fishes Poecilia
      spp.
AB  - The present study investigated the spatiotemporal patterns in trophic resource
      use in a system of a gynogenetic poeciliid fish, the Amazon molly Poecilia
      formosa, and its sexual congeners the sailfin molly Poecilia latipinna and the
      Atlantic molly Poecilia mexicana using gut contents analysis. No statistically
      significant differences in trophic resource use were found between sexual and
      gynogenetic species, but gut contents varied significantly across sites and over
      time. In addition, variation in trophic morphology (i.e. gut length) was
      significant across sites but not species, and laboratory experiments indicated
      that gut length is phenotypically plastic. Overall, trophic differentiation
      between coexisting asexual and sexual Poecilia appears to be minimal, and it is
      unlikely that niche differentiation contributes to a stable coexistence of the
      two reproductive forms.

PMID- 22141887
TI  - Biomechanics of swimming in the pufferfish Diodon holocanthus: propulsive
      momentum enhancement is an adaptation for thrust production in an undulatory
      median and paired-fin swimmer.
AB  - A form of large-amplitude elongated-body theory appropriate for the analysis of
      undulatory fins attached to a rigid body of elliptical section suggests a benefit
      due to momentum enhancement relative to the fins on their own. This theoretical
      prediction is experimentally confirmed for the first time. Theoretical momentum
      enhancement factors for Diodon holocanthus (2.2 and 2.7 for the median and
      pectoral fins, respectively) compared well to inferred thrust values determined
      from particle-image velocimetry (PIV) wake measurements (2.2-2.4 and 2.7-2.9).
      Caudal fin mean theoretical thrust was not significantly different from measured
      (PIV) values (n = 24, P > 0.05), implying no momentum enhancement. Pectoral-fin
      thrust was half that of the median and caudal fins due to high fin-jet angles,
      low circulation and momentum. Average total fin thrust and fish drag were not
      significantly different (n = 24, P > 0.05). Vortex rings generated by the fins
      were elliptical, with size dependent on fin chord and stroke amplitude.
      Hydrodynamic advantages (thrust enhancement at no cost to hydrodynamic
      efficiency, reduction of side forces minimizing energy wasting yawing motions and
      body drag) are probably common among rigid-bodied organisms propelled by
      undulatory fins. A trade-off between momentum enhancement and the rate of
      momentum generation (thrust force) sets a practical limit to the former. For
      small fins whilst momentum enhancement is high, absolute thrust is low. In
      addition, previously suggested limitations on thrust enhancement set by
      reductions in propulsive force associated with progressive reductions in fin
      wavelength are found to be biologically unrealistic.

PMID- 22141888
TI  - Feeding strategy and cannibalism of the Argentine hake Merluccius hubbsi.
AB  - The diet composition and feeding strategy of the Argentine hake Merluccius hubbsi
      in the San Matias Gulf were analysed in order to use this information for the
      sustainable management of the fishery. Merluccius hubbsi behaved as an
      opportunistic predator. Small M. hubbsi consumed planktonic crustaceans, whereas
      medium and large fish ate numerous prey taxa with low frequency of occurrence and
      variable specific abundance. Intra- and intercohort cannibalism were detected in
      all size groups and were particularly significant in large M. hubbsi. Medium
      sized M. hubbsi consumed small conspecifics and large-sized M. hubbsi consumed
      both small and medium M. hubbsi. These results indicate that the removal of large
      M. hubbsi by fishing may increase the risk of overfishing by two combined
      effects: a direct effect of recruitment-overfishing and an indirect effect of
      growth-overfishing through an enhanced cannibalism of medium M. hubbsi on small
      M. hubbsi. Intra- and intercohort cannibalism and other trophic relationships in
      the M. hubbsi should therefore be considered explicitly in stock assessment
      models.

PMID- 22141889
TI  - A temperature-dependent growth model for the three-spined stickleback
      Gasterosteus aculeatus.
AB  - Specific growth rates of individually reared juvenile three-spined sticklebacks
      Gasterosteus aculeatus were investigated under laboratory conditions to
      parameterize a complete temperature-dependent growth model for this species. To
      test the applicability of experimentally derived optima in growth response rates
      to natural conditions, the effects of commercial pellets and natural prey on
      growth rates were investigated. In addition, to test for seasonal effects on
      growth, laboratory trials were performed in both spring and winter. Growth took
      place from 5 to 29 degrees  C with a temperature for optimum growth reaching a
      sharp peak at 21 degrees  C. Modelled optimal temperature for maximum growth was
      estimated to be 21.7 degrees  C and lower and upper temperatures for growth were
      estimated to be 3.6 and 30.7 degrees  C, respectively. There were no significant
      differences in growth rates between fish reared on invertebrates or commercial
      pellets. Seasonal effects on growth were pronounced, with reduced growth rates in
      the winter despite similar laboratory conditions. On average, 60% higher growth
      rates were achieved at the optimum temperature in summer compared to the winter.
      The strong seasonality in the growth patterns of G. aculeatus indicated here
      reduces the applicability of the model derived in this study to spring and summer
      conditions.

PMID- 22141890
TI  - Hybridization between pallid sturgeon Scaphirhynchus albus and shovelnose
      sturgeon Scaphirhynchus platorynchus.
AB  - This study found that introgressive hybridization of the pallid sturgeon
      Scaphirhynchus albus with the common shovelnose sturgeon Scaphirhynchus
      platorynchus has probably occurred across the range of S. albus. Bayesian
      clustering found evidence of hybridization in all management units of S. albus.
      Some individuals were intermediate at both genetic and morphological characters,
      and some had discordant results. The results support introgressive hybridization
      throughout much of the range of S. albus, yet individuals consistent with being
      pure members of each species were detected in all management units. Simulations
      demonstrated that it would be very difficult to distinguish introgressed
      individuals from pure specimens after multiple generations of backcrossing with
      these microsatellite markers. Using hybrid or backcross fish as broodstock could
      artificially accelerate the loss of unique genetic variation in S. albus.
      Additional microsatellite loci or additional genetic markers, along with
      morphological data may be required to ensure that hybrid or backcross fish are
      not used. Introgressive hybridization requires at least two generations and
      generation lengths of S. albus are long, perhaps as long as 30 years. The
      proportion of individuals consistent with introgressive hybrid origins indicates
      that hybridization between S. albus and S. platorynchus probably has occurred for
      several generations and is not a recent phenomenon.

PMID- 22141891
TI  - Metazoan parasite communities of rock cod Eleginops maclovinus along southern
      Chilean coast and their use as biological tags at a local spatial scale.
AB  - The composition of the metazoan parasite fauna of the rock cod Eleginops
      maclovinus from three locations in southern Chile was compared to assess the
      local spatial variation of the community component of their parasitic faunas. A
      total of 13 108 metazoan parasites (5267 endoparasites and 7841 ectoparasites)
      belonging to 34 taxa were collected from 268 specimens of E. maclovinus between
      October 2008 and March 2009. The populations and community quantitative
      descriptors were estimated. Altogether, 97.4% of the fish were infected with at
      least one parasite taxon. The most prevalent species were Hypoechinorhynchus
      magellanicus (Acanthocephala), Caligus rogercresseyi, Lepeophtheirus mugiloides,
      Clavella adunca (Copepoda) and Similascarophis sp. (Nematoda). Five species are
      new records for this host: Argulus araucanus, Hirudinea gen. sp1., Hirudinea gen.
      sp2., Benedenia sp. and Camallanidae gen. sp. A linear discriminant analysis
      (LDA) showed that the metazoan parasite fauna of E. maclovinus varied
      qualitatively and quantitatively among three locations, with 89.7% of fish being
      correctly assigned to their respective locations. This suggested that parasites
      could be a reliable tool to discriminate individual fish from geographically
      close locations. There was a weak relationship between the parasite fauna and
      fish size and there were no accumulations of parasites in the host over time,
      which could be associated with ontogenetic changes of diet associated with
      habitat use.

PMID- 22141892
TI  - The feeding ecology of 0 year-group turbot Scophthalmus maximus and brill
      Scophthalmus rhombus on Irish west coast nursery grounds.
AB  - On sandy beach nursery grounds along the west coast of Ireland, 0 year-group
      turbot Scophthalmus maximus were found to consume six types of crustaceans, in
      addition to polychaetes. The 0 year-group brill Scophthalmus rhombus fed almost
      exclusively on mysids, even though nine taxonomic prey groups were identified in
      the sediment across the investigated beaches. Both species avoided non-motile
      organisms such as gastropods and bivalves, which were present in high abundances
      in the sediment and their growth and condition was not significantly related to
      the quantity or type of prey consumed, temperature or salinity. A high incidence
      of feeding was detected for both species over the duration of the study,
      suggesting that food was not limiting on west of Ireland nursery grounds.
      Temporal partitioning of settlement was detected between S. maximus and S.
      rhombus, indicating that inter-specific competition for food does not occur
      between these two flatfish species on west of Ireland nursery grounds.

PMID- 22141893
TI  - Visual acuity of snapper Pagrus auratus: effect of size and spectral composition.
AB  - Visual acuity of the commercially important sparid Pagrus auratus was tested
      using the optomotor response. Juvenile fish were categorized by size as group 1
      (50 g), group 2 (100 g), group 3 (150 g), group 4 (300 g), group 5 (500 g) and
      group 6 (800 g). Group 3 fish demonstrated excellent visual acuity (minimum
      separable angle, M(SA), 1 degrees ), which was improved compared with the smaller
      fish groups (groups 1 and 2, M(SA), 2 degrees ). In the larger fish groups,
      however, a reduction in visual acuity was observed (groups 4, 5 and 6 M(SA), 4
      degrees ). Group 2 (100 g) fish displayed positive optomotor responses in long
      wavelength light (red) but reduced responses in short wavelengths (blue). Red
      light sensitivity is beneficial for the estuarine lifestyle of these fish, where
      light is predominantly at long wavelengths. In contrast, group 6 (800 g) fish
      displayed improved acuity in blue and green light and reduced acuity in red
      light. Fish of this size move away from the estuary to open oceans, where light
      is predominantly in the shorter wavelengths (blue-green). These results support
      the sensitivity hypothesis for the relationship between fish visual systems and
      the light environment they inhabit.

PMID- 22141894
TI  - Size-dependent prey selection in piscivorous pikeperch Sander lucioperca and
      Volga pikeperch Sander volgensis shaped by bimodal prey size distribution.
AB  - Prey size and species selection of pikeperch Sander lucioperca and Volga
      pikeperch Sander volgensis were investigated in relation to predator size in the
      shallow Lake Balaton, Hungary. Although their gape sizes were similar, S.
      lucioperca shifted to piscivory earlier and consumed fewer, but larger, prey than
      S. volgensis. Prey species preference of the two piscivores also differed. A
      bimodal prey size distribution resulted in a reclining sigmoid curve for the life
      span predator size to prey size relationship with inflexion points between 266
      and 284 mm predator standard length (L(S) ) in S. lucioperca. In S. volgensis, as
      well as in S. lucioperca L(S) <= 350 mm, prey size increased monotonically with
      predator L(S) , following a power trend for all prey size variables. Prey depth
      to predator L(S)  relationship varied significantly with prey species and prey
      number in both piscivores, and prey depth tended to be smaller in predators
      consuming more than one prey. Both predator species characteristically selected
      less active, benthic prey fishes in spite of their spiny fin rays, and small- and
      mid-sized predators selected for small prey. Relatively large prey were also
      eaten, however, especially by the smallest and largest S. lucioperca.

PMID- 22141895
TI  - Macrobenthic prey availability and the potential for food competition between 0
      year group Pleuronectes platessa and Limanda limanda.
AB  - This study describes the feeding habits of plaice Pleuronectes platessa and dab
      Limanda limanda during early juvenile development and relates differences between
      nursery grounds and sampling years to spatial and temporal variabilities in
      macrobenthic prey availability. The main prey taxa of both species were copepods,
      bivalves, amphipods, polychaetes and oligochaetes and size-related variation in
      diet was found. Despite considerable similarity in the prey items, differences in
      food composition between the two species were observed and spatial variability in
      diet confirmed their opportunistic feeding behaviour. A high degree of dietary
      overlap was found in June and decreased steadily throughout the season. The prey
      composition in the guts of both species largely reflected the composition of the
      main macrobenthic taxa in the sediment. The overall data suggest that resources
      were not limiting in the littoral sandy nursery areas in the west of Ireland and
      no indications were found that exploitative competitive forces upon the benthic
      prey assemblages occurred between P. platessa and L. limanda. Feeding success,
      Fulton's K condition and dietary overlap, however, showed spatial and temporal
      variations, and were probably affected by the availability and density of
      macrobenthic prey.

PMID- 22141896
TI  - Parameterization of European perch Perca fluviatilis length-at-age data using
      stochastic Gompertz growth models.
AB  - Three stochastic versions of the Gompertz growth model were used to parameterize
      total length (L(T) )-at-age data for perch Perca fluviatilis, an important target
      species for commercial and recreational fishers and a food species for predatory
      fishes and aquatic birds. Each model addresses growth heterogeneity by
      incorporating random parameters from a specific positive distribution: Weibull,
      gamma or log-normal. The modelling outputs for each version of the model provide
      L(T)  distributions for selected ages and percentiles of L(T)  at age for both
      males and females. The results highlight the importance of using a stochastic
      approach and the logistic-like growth pattern for analysing growth data for P.
      fluviatilis in Curonian Lagoon (Lithuania). Outputs from this modelling can be
      extended to a stochastic analysis of fish cohort dynamics, incorporating all
      length-based biological relationships, and the selectivity-related interactions
      between fish cohorts and fishing gear.

PMID- 22141897
TI  - Genetic divergence among native trout Salmo trutta populations from southern
      Balkans based on mitochondrial DNA and microsatellite variation.
AB  - The genetic structure and the phylogenetic relationships among five Balkan
      populations of trout Salmo trutta that have been classified earlier into five
      different taxa were studied, using microsatellite and mitochondrial DNA (mtDNA)
      analyses. The pattern of population differentiation observed at microsatellites
      differed to that depicted by mtDNA variation, yet both methods indicated a very
      strong partitioning of the genetic variation among sampling locations. Results
      thus suggest that conservation strategies should be directed towards preserving
      the genetic integrity and uniqueness of each population.

PMID- 22141898
TI  - Effect of salinity on growth of Abant trout Salmo trutta abanticus.
AB  - Abant trout Salmo trutta abanticus were grown for 154 days at three salinities of
      0, 9 or 18 to assess mass gain, condition factor, food conversion ratio and food
      consumption. Appetite was significantly higher at 0 than at salinities of 9 or
      18. Salinities >18 may have detrimental effects on biomass production. The mean
      +/- S.E. of the condition factor at the three salinities were 1.29 +/- 0.20 at 0,
      1.22 +/- 0.22 at 9 and 1.10 +/- 0.20 at 18. Fish reared at a salinity of 0 showed
      higher mass gain, food conversion ratio and food consumption.

PMID- 22141899
TI  - Does sympatry affect trophic resource use in congeneric tidepool fishes? A tale
      of two gobies Favonigobius lentiginosus and Favonigobius exquisitus.
AB  - The feeding ecology of two sympatric gobies, Favonigobius lentiginosus and
      Favonigobius exquisitus, which inhabit soft substrate pools was studied in
      Moreton Bay, Australia. Favonigobius spp. and sediment cores were collected from
      three locations within the bay and fish gut contents were analysed to explore
      potential competition and ontogenetic dietary shifts. The most abundant prey at
      all sites was nematodes at 6.33 +/- 0.38 cm(-3) at Dunwich, 33.58 +/- 0.26 cm(-3)
      at Manly and 6.36 +/- 0.849 cm(-3) (mean +/- S.E.) at Godwin Beach. Nevertheless,
      they were not a dominant component of the diets. Volumetric percent contribution
      of prey showed that copepods and decapod shrimps dominated F. lentiginosus diets
      at Dunwich (7.8 and 6.6%, respectively) and Godwin Beach (6.5 and 14.3%,
      respectively) and the diets of F. exquisitus at Manly (9.2 and 9.5%,
      respectively) and Godwin Beach (10.4 and 11.8%, respectively). Schoener's index
      of dietary overlap between the two species, when sympatric, was 0.85 indicating a
      high similarity. An ontogenetic shift towards larger prey items occurred as
      Favonigobius spp. reached larger sizes. Gut fullness indices showed significant
      differences between time of day (two-way ANOVA, P < 0.01) and species (two-way
      ANOVA, P < 0.05) but Bonferroni's multiple comparison test showed that the only
      significant difference was between F. lentiginosus at Dunwich and F. exquisitus
      at Godwin Beach at 1800 hours. Food resource competition and temporal resource
      partitioning did not appear to be a limiting factor between F. lentiginosus and
      F. exquisitus despite cohabitation in such restricted environments.

PMID- 22141900
TI  - Reef fish structure and distribution in a south-western Atlantic Ocean tropical
      island.
AB  - The community structure of the reef fish fauna of Trindade Island, a volcanic
      oceanic island located 1160 km off the coast of Brazil, is described based on
      intensive visual censuses. Seventy-six species were encountered in 252 censuses,
      with mean +/- S.E. of 99 +/- 3 individuals and 15.7 +/- 0.3 species 40 m(-2)
      transect. The average fish biomass, calculated from length-class estimation, was
      22.1 kg 40 m(-2) transect. The species contributing most to biomass were, in
      decreasing order, Melichthys niger, Cephalopholis fulva, Kyphosus spp.,
      Holocentrus adscensionis, Sparisoma amplum, Sparisoma axillare, Acanthurus
      bahianus and Epinephelus adscensionis. Carnivorous fishes were the largest
      trophic group in terms of biomass, followed by omnivores and roving herbivores.
      The two predominant types of reef habitat, fringing reefs built by coralline
      algae and rocky reefs made of volcanic boulders, showed significant differences
      in the biomass and the abundance of the trophic guilds. Within each habitat type,
      significant differences in species richness, density and biomass were detected
      among crest, slope and interface zones. Although similar in overall species
      composition to coastal reefs in Brazil, the fish fauna of Trindade Island shares
      certain characteristics, such as a high abundance of planktivores, with other
      Brazilian oceanic islands. Despite comparatively high fish biomass, including the
      macro-carnivorous species habitually targeted by fisheries, signs of overfishing
      were evident. These findings highlight the urgency for a conservation initiative
      for this isolated, unique and vulnerable reef system.

PMID- 22141901
TI  - Ontogeny of antipredator performance in hatchery-reared Japanese anchovy
      Engraulis japonicus larvae exposed to visual or tactile predators in relation to
      turbidity.
AB  - Laboratory experiments revealed distinct effects of turbidity on the survival of
      Japanese anchovy Engraulis japonicus larvae when exposed to either visual (jack
      mackerel Trachurus japonicus) or tactile (moon jellyfish Aurelia aurita)
      predators. The experiments were conducted in 30 l tanks with three levels of
      turbidity obtained by dissolving 0, 50 or 300 mg l(-1)  of kaolin. Predators were
      introduced to experimental tanks followed by larvae of E. japonicus ranging from
      5 to 25 mm standard lengths (L(s) ). When exposed to T. japonicus, the mean
      survival rate of larvae was significantly higher in 300 mg l(-1)  treatments
      compared to the other turbidity levels. When exposed to A. aurita, however, there
      was no difference in the survival rates among different turbidity treatments. The
      survival rates when exposed to either predator improved with larval growth. The
      logistic survivorship models for E. japonicus larvae when exposed to A. aurita
      had an inflection point at c. 12 mm L(s) , suggesting that their size refuge from
      A. aurita is close to this value. Comparison to a previous study suggests a high
      vulnerability of shirasu (long and transparent) fish larvae to jellyfish
      predation under turbidity. This study indicates that anthropogenic increases of
      turbidity in coastal waters may increase the relative effect of jellyfish
      predation on fish larvae.

PMID- 22141902
TI  - Quantitative genetic analysis of the physiological stress response in three
      strains of brook charr Salvelinus fontinalis and their hybrids.
AB  - Three strains [domestic (D), Laval (L) and Rupert (R)] of brook charr Salvelinus
      fontinalis and their reciprocal hybrids were submitted to transport stress to
      measure stress resistance. Primary (cortisol) and secondary (glucose, osmolality
      and haematocrit) stress responses were measured for each cross. Significant
      heritabilities were observed for both levels of stress response, with mean +/-
      S.E. heritability (h(2)) = 0.60 +/- 0.20 for plasma cortisol and 0.61 +/- 0.20
      for plasma glucose. There were strain differences whereby the R strain was the
      least sensitive to stress at the primary and secondary levels. No heterosis was
      detected, and only one case of outbreeding depression was present. The
      outbreeding depression was observed in the D(?) R(?) hybrid, which had a 27%
      increase of plasma glucose compared to parental strains. The D(?) R(?) and R(?)
      L(?) hybrids had more pronounced variations (increase or decrease) in plasma
      osmolality than their respective parental strains, but these variations were
      difficult to relate definitively with the potential secondary stress response.
      These results indicate a strong potential for genetic improvement in the stress
      response to transport with the use of purebred crosses while hybridization has
      little value in this regard.

PMID- 22141903
TI  - Interdecadal and spatial variations of diet composition in horse mackerel
      Trachurus trachurus.
AB  - Interdecadal variability of the diet composition of horse mackerel Trachurus
      trachurus was examined through analysis of the stomach contents of fish collected
      from the north-west and south of Portugal during 1990-1992 and 2005-2006. These
      decades correspond to periods of high and low feeding intensity of T. trachurus.
      Dietary composition of adult T. trachurus was assessed by determining the
      frequency of occurrence and biovolume of identified prey, and these two variables
      were combined to estimate an index of relative importance of prey. Dietary
      composition differed between areas, seasons and, in particular, decades. The most
      important prey in 1990-1992 were euphausiids while in 2005-2006 the most
      important prey were fishes. Results show that periods of different feeding
      intensity for T. trachurus are characterized by diets with different dominant
      prey items, suggesting that a description of the diet of a fish species is not
      complete if only based on samples collected in a limited space and time period.
      This result has implications for the study of marine trophic food webs, since a
      generalist predator may easily and rapidly change its trophic niche, to adapt to
      different prey abundance and availability.

PMID- 22141904
TI  - Formation of a fluvial non-parasitic population of Lethenteron camtschaticum as
      the first step in petromyzontid speciation.
AB  - To elucidate the petromyzontid speciation process, the genetic independence of
      the fluvial non-parasitic populations within the anadromous parasitic Lethenteron
      camtschaticum was estimated by using polymorphic microsatellite loci. Abundant
      gene flow was revealed in multitemporal scales between potentially sympatric
      populations, suggesting ongoing gene flow resulting from imperfect size
      assortative mating between them and plastic determination of life histories. On
      the contrary, landlocked fluvial non-parasitic populations in the upper region of
      dams were genetically divergent from anadromous parasitic populations. The
      temporal heterogeneity of gene flow, i.e. contemporary little gene flow but
      significant gene flow over the long-term between the landlocked fluvial non
      parasitic and anadromous parasitic populations was elucidated. In addition, the
      divergence time of isolation of the landlocked populations from the ancestral
      anadromous parasitic population was estimated to have occurred 17.9-428.2 years
      ago, which includes the construction times of an initial dam c. 90 years ago.
      These instances indicate that the landlocked populations should have very
      recently been established, and subsequent accumulation of divergence and
      development of reproductive isolation are predicted. The present landlocked
      fluvial non-parasitic populations should be analogous to the founder populations
      in terms of petromyzontid speciation. The data also strongly support the
      hypothesis of multitemporal and multispatial speciation in the petromyzontid stem
      satellite species complex.

PMID- 22141905
TI  - Lipid correction model of carbon stable isotopes for a cosmopolitan predator,
      spiny dogfish Squalus acanthias.
AB  - Three lipid correction models were evaluated for liver and white dorsal muscle
      from Squalus acanthias. For muscle, all three models performed well, based on the
      Akaike Information Criterion value corrected for small sample sizes (AIC(c) ),
      and predicted similar lipid corrections to delta(13) C that were up to 2.8 0/00
      higher than those predicted using previously published models based on
      multispecies data. For liver, which possessed higher bulk C:N values compared to
      that of white muscle, all three models performed poorly and lipid-corrected
      delta(13) C values were best approximated by simply adding 5.74 0/00 to bulk
      delta(13) C values.

PMID- 22141906
TI  - Carbohydrates in rod and cone light absorbing segments in the firemouth cichlid
      Thorichthys meeki retina.
AB  - Carbohydrates in photoreceptor segments in the retina of the firemouth cichlid
      Thorichthys meeki are described and compared. The present periodic acid-Schiff
      (PAS) and lectin results revealed the occurrence of neutral carbohydrates,
      composed mainly of glycosamine and mannose and glucose, in the light absorbing
      segments in rods and cones in this species. Unlike in mammals, the retina in this
      teleost seems to be poor in galactose and galactose-galactosamine units in the
      light absorbing segments.

PMID- 22141907
TI  - Census (N C) and genetically effective (N e) population size in a lake-resident
      population of brown trout Salmo trutta.
AB  - Census (N(C)) and effective population size (N(e)) were estimated for a lake
      resident population of brown trout Salmo trutta as 576 and 63, respectively. The
      point estimate of the ratio of effective to census population size (N(e):N(C))
      for this population is 0.11 with a range of 0.06-0.26, suggesting that N(e):N(C)
      ratio for lake-resident populations agree more with estimates for fishes with
      anadromous life histories than the small ratios observed in many marine fishes.

PMID- 22141908
TI  - Bactericidal activity of grass carp Ctenopharyngodon idella C9-deficient serum
      against Aeromonas hydrophila.
AB  - Neutralizing complement C9 in grass carp Ctenopharyngodon idella sera with rabbit
      anti-C9 sera against fish complement C9, demonstrated that bactericidal activity
      against Aeromonas hydrophila of the C9-deficient fish sera was greatly impaired.
      These results indicated that the fish complement C9 plays a key role in pathogen
      killing through the lytic pathway.

PMID- 22141909
TI  - First report of the Taiwan sardinella Sardinella hualiensis (Clupeiformes:
      Clupeidae) in the Philippines.
AB  - A range expansion of the Taiwan sardinella Sardinella hualiensis to the
      Philippines is reported. The data suggested that the southern translocation of S.
      hualiensis occurred across oceanographic features that are typically barriers to
      small, pelagic fish dispersal. With this addition, the Philippines is among the
      most diverse countries for Sardinella biodiversity in the world, second only to
      India.

PMID- 22141910
TI  - Extreme homogeneity and low genetic diversity in Kryptolebias ocellatus from
      south-eastern Brazil suggest a recent foundation for this androdioecious fish
      population.
AB  - This study documents unexpectedly low levels of intra and interpopulation genetic
      diversity in Kryptolebias ocellatus, an androdioecious and predominantly self
      fertilizing killifish from south-eastern Brazil. This finding generally is
      inconsistent with the established opinion that the K. ocellatus and K. marmoratus
      clade originated in this geographic region and later dispersed northward into the
      Caribbean.

PMID- 22141914
TI  - A microanalytical study of the surfaces of normal, delipidized, and artificially
      "resurfaced" articular cartilage.
AB  - The surface amorphous layer of articular cartilage is of primary importance to
      its load-bearing and lubrication function. This lipid-filled layer is
      degraded/disrupted or eliminated when cartilage degenerates due to diseases. This
      article examines further the characteristic of this surface overlay using a
      combination of microscopy and imaging methods to evaluate the hypothesis that the
      surface of articular cartilage can be repaired by exposing degraded cartilage to
      aqueous synthetic lipid mixtures. The preliminary results demonstrate that it is
      possible to create a new surface layer of phospholipids on the surface of
      cartilage following artificial lipid removal, but such a layer does not possess
      enough mechanical strength for physiological function when created with either
      unsaturated palmitoyl-oleoyl-phosphatidylcholine or saturated dipalmitoyl
      phosphatidylcholine component of joint lipid composition alone. We conclude that
      this may be due to low structural cohesivity, inadequate time of exposure, and
      the mix/content of lipid in the incubation environment.

PMID- 22141913
TI  - A combinatorial in silico and cellular approach to identify a new class of
      compounds that target VEGFR2 receptor tyrosine kinase activity and angiogenesis.
AB  - BACKGROUND AND PURPOSE: Vascular endothelial growth factor receptor 2 (VEGFR2) is
      an attractive therapeutic target for the treatment of diseases such as cancer.
      Small-molecule VEGFR2 inhibitors of a variety of chemical classes are currently
      under development or in clinical use. In this study, we describe the de novo
      design of a new generation pyrazole-based molecule (JK-P3) that targets VEGFR2
      kinase activity and angiogenesis. EXPERIMENTAL APPROACH: JK-P compound series
      were designed using de novo structure-based identification methods. Compounds
      were tested in an in vitro VEGFR2 kinase assay. Using primary endothelial cells,
      JK-P compounds were assessed for their ability to inhibit VEGF-A-stimulated
      VEGFR2 activation and intracellular signalling. We tested these compounds in cell
      migration, proliferation and angiogenesis assays. KEY RESULTS: JK-P3 and JK-P5
      were predicted to bind the VEGFR2 kinase domain with high affinity, and both
      compounds showed pronounced inhibition of endogenous VEGFR2 kinase activity in
      primary human endothelial cells. Only JK-P3 inhibited VEGF-A-stimulated VEGFR2
      activation and intracellular signalling. Interestingly, JK-P3 inhibited
      endothelial monolayer wound closure and angiogenesis but not endothelial cell
      proliferation. Both compounds inhibited fibroblast growth factor receptor kinase
      activity in vitro, but not basic fibroblast growth factor-mediated signalling in
      endothelial cells. CONCLUSIONS AND IMPLICATIONS: This is the first report that
      describes an anti-angiogenic inhibitor based on such a pyrazole core. Using a de
      novo structure-based identification approach is an attractive method to aid such
      drug discovery. These results thus provide an important basis for the development
      of multi-tyrosine kinase inhibitors for clinical use in the near future.

PMID- 22141915
TI  - Comprehensive screening study of pesticide degradation via oxidation and
      hydrolysis.
AB  - This comprehensive study focused on the reactivity of a set of 62 pesticides via
      oxidization by free chlorine, monochloramine, chlorine dioxide, hydrogen
      peroxide, ozone, and permanganate; photodegradation with UV(254); and hydrolysis
      at pH 2, 7, and 12. Samples were analyzed using direct injection liquid
      chromatography-mass spectrometry detection or gas chromatography-electron capture
      detection after liquid-liquid extraction. Many pesticides were reactive via
      hydrolysis and/or chlorination and ozonation mechanisms under typical drinking
      water treatment conditions, with less reactivity exhibited on average for
      chlorine dioxide, monochloramine, hydrogen peroxide, and UV(254). The pyrazole
      and organophosphorous pesticides were most reactive in general, whereas
      carbamates and others were less reactive. The screening study provides guidance
      for the pesticide/oxidation systems that are most likely to lead to degradates in
      water treatment and the environment.

PMID- 22141916
TI  - Renal impairment is not an independent adverse prognostic factor in patients with
      multiple myeloma treated upfront with novel agent-based regimens.
AB  - Abstract   Renal impairment (RI) is a common presenting complication of multiple
      myeloma associated with significant morbidity and early mortality, while it has
      been associated with inferior survival in patients treated with conventional
      regimens. We assessed the impact of RI in 203 unselected consecutive patients
      treated upfront with novel agents (thalidomide, lenalidomide, bortezomib). RI was
      assessed by the estimated glomerular filtration rate (eGFR). RI (eGFR <60 mL/min)
      was present in 93 (45.8%) of patients at diagnosis and was associated with
      advanced age, advanced International Staging System (ISS) stage, poorer
      performance status, hypercalcemia, urine Bence-Jones proteinuria, anemia and
      thrombocytopenia. Myeloma response rates were similar for patients with or
      without RI. In univariate analysis RI was associated with shorter survival and a
      higher rate of early death (7% vs. 3.5%); however, when adjusted for other
      prognostic factors, RI was not independently associated with survival. In
      conclusion, in unselected newly diagnosed patients treated with novel agent-based
      therapies, RI is not independently associated with inferior survival, probably
      due to the significant activity of novel agents even in the context of RI.

PMID- 22141917
TI  - Acupuncture therapy for infants: a preliminary report on reasons for
      consultation, feasibility, and tolerability.
AB  - OBJECTIVES/AIMS:   The aim of this retrospective review was to determine the
      feasibility, safety, and potential therapeutic effects of acupuncture in an
      inpatient infant population and to obtain data that would support the design of a
      randomized, controlled trial of acupuncture in infants. BACKGROUND:  
      Hospitalized infants are often exposed to sedative and analgesic medications to
      facilitate intensive and invasive medical care. With increasing concern about the
      potential neurotoxic effects of common analgesic and sedative medications,
      minimizing an infant's exposure to such agents is desirable. Acupuncture can be
      therapeutic in adults and children, but data in infants are lacking.
      METHODS/MATERIALS:   We performed a retrospective chart review of infants who
      received acupuncture during hospitalizations between 2008 and 2010. Demographic
      data, diagnoses, reason for acupuncture consult, ventilator settings,
      sedative/analgesic medication regimens, details of acupuncture therapy, and
      adverse effects were among data collected. RESULTS:   Ten infants were identified
      in this review, seven of whom had agitation issues, two of whom had feeding
      difficulties, and one had both symptoms. Six of the eight infants with agitation
      had a decrease in the use of sedative and analgesic medications over the
      acupuncture therapy period, and four of five initially requiring mechanical
      ventilation were successfully weaned. One of the three infants with oral aversion
      transitioned rapidly to oral intake. Acupuncture therapy was well tolerated, and
      there were no complications observed. CONCLUSIONS:   In this small group of
      hospitalized infants, acupuncture was found to be safe, well tolerated, and
      therapeutic. More studies are warranted to define the role of acupuncture in this
      population.

PMID- 22141918
TI  - A functional hybrid memristor crossbar-array/CMOS system for data storage and
      neuromorphic applications.
AB  - Crossbar arrays based on two-terminal resistive switches have been proposed as a
      leading candidate for future memory and logic applications. Here we demonstrate a
      high-density, fully operational hybrid crossbar/CMOS system composed of a
      transistor- and diode-less memristor crossbar array vertically integrated on top
      of a CMOS chip by taking advantage of the intrinsic nonlinear characteristics of
      the memristor element. The hybrid crossbar/CMOS system can reliably store complex
      binary and multilevel 1600 pixel bitmap images using a new programming scheme.

PMID- 22141919
TI  - Palladium-catalyzed direct arylation of polysubstituted benzofurans.
AB  - An efficient access to 2-substituted 3-arylbenzofurans through a palladium
      catalyzed C3 direct arylation of 2-substituted benzofurans with aryl bromides is
      described. The scope and limitation of this reaction was studied. The method
      tolerates a variety of functional groups on the aryl halide and has been
      successfully extended to polysubstituted benzofurans to obtain the corresponding
      3-arylbenzofurans with good to excellent yields.

PMID- 22141920
TI  - The calculus of unsustainability.

PMID- 22141921
TI  - A rational analysis of the acquisition of multisensory representations.
AB  - How do people learn multisensory, or amodal, representations, and what
      consequences do these representations have for perceptual performance? We address
      this question by performing a rational analysis of the problem of learning
      multisensory representations. This analysis makes use of a Bayesian nonparametric
      model that acquires latent multisensory features that optimally explain the
      unisensory features arising in individual sensory modalities. The model
      qualitatively accounts for several important aspects of multisensory perception:
      (a) it integrates information from multiple sensory sources in such a way that it
      leads to superior performances in, for example, categorization tasks; (b) its
      performances suggest that multisensory training leads to better learning than
      unisensory training, even when testing is conducted in unisensory conditions; (c)
      its multisensory representations are modality invariant; and (d) it predicts
      ''missing" sensory representations in modalities when the input to those
      modalities is absent. Our rational analysis indicates that all of these aspects
      emerge as part of the optimal solution to the problem of learning to represent
      complex multisensory environments.

PMID- 22141922
TI  - Early childhood experiences, parenting and the process of drug dependency among
      young people in Tehran, Iran.
AB  - INTRODUCTION AND AIMS: Substance abuse has become a major public health problem
      in Iran. The process of developing an addiction is complex and multifaceted.
      Early childhood experiences are thought to be one of the important determinants
      of addictive behaviour. The aim of this qualitative study is to explore the early
      childhood experiences, especially the experiences within the immediate family, of
      current substance-using young adults in Iran. DESIGN AND METHODS: The study is
      qualitative in nature. In-depth interviews were conducted with 15 young men and
      women who were either in treatment for their addiction or were active drug users
      at the time of the interviews. Moreover, four interviews have been conducted with
      family members of participants. RESULTS: The majority of the participants
      experienced traumatic events during childhood and came from dysfunctional
      families. There appears to be a significant disconnect between these individuals
      and their families. An obedience-instilling parenting style and parents'
      knowledge and attitude toward drug using and prevention were also identified as
      important determinants of substance use. DISCUSSION AND CONCLUSIONS: The results
      of this research point out the need for early interventions for at-risk families
      as well as at-risk individuals.

PMID- 22141923
TI  - Two distinct RNA-dependent RNA polymerases are required for initiation and
      amplification of RNA silencing in the basal fungus Mucor circinelloides.
AB  - RNA-dependent RNA polymerases (RdRPs) play key roles in the RNA silencing pathway
      in a number of organisms. They have been involved in the production of double
      stranded RNA (dsRNA) molecules that initiate the silencing mechanism as well as
      in the amplification of the silencing signal. The roles of RdRPs from fungi in
      these processes are poorly described compared with other eukaryotes. RNA
      silencing in the zygomycete Mucor circinelloides exhibits uncommon features, such
      as induction by self-replicative sense transgenes and an amplification process
      associated with two size classes of antisense small interfering RNAs (siRNAs). To
      investigate the function of fungal RdRP proteins in initiation and amplification
      of silencing we have cloned and characterized two different rdrp genes in M.
      circinelloides. Functional analysis of rdrp(-) disruption mutants indicates that
      rdrp-1 is essential for initiation of silencing by sense transgenes by producing
      antisense RNA transcripts derived from the transgene, but it is not necessary for
      amplification of the silencing signal, whereas rdrp-2 is required for efficient
      accumulation of the two different classes of secondary siRNAs regardless the
      nature of the trigger. Our results provide evidence for a functional
      diversification of M. circinelloides rdrp genes in different steps of the same
      RNA silencing pathway.

PMID- 22141925
TI  - Ships, ports and particulate air pollution - an analysis of recent studies.
AB  - The duration of use is usually significantly longer for marine vessels than for
      roadside vehicles. Therefore, these vessels are often powered by relatively old
      engines which may propagate air pollution. Also, the quality of fuel used for
      marine vessels is usually not comparable to the quality of fuels used in the
      automotive sector and therefore, port areas may exhibit a high degree of air
      pollution. In contrast to the multitude of studies that addressed outdoor air
      pollution due to road traffic, only little is known about ship-related air
      pollution. Therefore the present article aims to summarize recent studies that
      address air pollution, i.e. particulate matter exposure, due to marine vessels.
      It can be stated that the data in this area of research is still largely limited.
      Especially, knowledge on the different air pollutions in different sea areas is
      needed.

PMID- 22141924
TI  - amoA-based consensus phylogeny of ammonia-oxidizing archaea and deep sequencing
      of amoA genes from soils of four different geographic regions.
AB  - Ammonia-oxidizing archaea (AOA) play an important role in nitrification and many
      studies exploit their amoA genes as marker for their diversity and abundance. We
      present an archaeal amoA consensus phylogeny based on all publicly available
      sequences (status June 2010) and provide evidence for the diversification of AOA
      into four previously recognized clusters and one newly identified major cluster.
      These clusters, for which we suggest a new nomenclature, harboured 83 AOA species
      level OTU (using an inferred species threshold of 85% amoA identity). 454
      pyrosequencing of amoA amplicons from 16 soils sampled in Austria, Costa Rica,
      Greenland and Namibia revealed that only 2% of retrieved sequences had no
      database representative on the species-level and represented 30-37 additional
      species-level OTUs. With the exception of an acidic soil from which mostly amoA
      amplicons of the Nitrosotalea cluster were retrieved, all soils were dominated by
      amoA amplicons from the Nitrososphaera cluster (also called group I.1b),
      indicating that the previously reported AOA from the Nitrosopumilus cluster (also
      called group I.1a) are absent or represent minor populations in soils. AOA
      richness estimates on the species level ranged from 8-83 co-existing AOAs per
      soil. Presence/absence of amoA OTUs (97% identity level) correlated with
      geographic location, indicating that besides contemporary environmental
      conditions also dispersal limitation across different continents and/or
      historical environmental conditions might influence AOA biogeography in soils.

PMID- 22141926
TI  - A fully-automatic caudate nucleus segmentation of brain MRI: application in
      volumetric analysis of pediatric attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Accurate automatic segmentation of the caudate nucleus in magnetic
      resonance images (MRI) of the brain is of great interest in the analysis of
      developmental disorders. Segmentation methods based on a single atlas or on
      multiple atlases have been shown to suitably localize caudate structure. However,
      the atlas prior information may not represent the structure of interest
      correctly. It may therefore be useful to introduce a more flexible technique for
      accurate segmentations. METHOD: We present CaudateCut: a new fully-automatic
      method of segmenting the caudate nucleus in MRI. CaudateCut combines an atlas
      based segmentation strategy with the Graph Cut energy-minimization framework. We
      adapt the Graph Cut model to make it suitable for segmenting small, low-contrast
      structures, such as the caudate nucleus, by defining new energy function data and
      boundary potentials. In particular, we exploit information concerning the
      intensity and geometry, and we add supervised energies based on contextual brain
      structures. Furthermore, we reinforce boundary detection using a new multi-scale
      edgeness measure. RESULTS: We apply the novel CaudateCut method to the
      segmentation of the caudate nucleus to a new set of 39 pediatric attention
      deficit/hyperactivity disorder (ADHD) patients and 40 control children, as well
      as to a public database of 18 subjects. We evaluate the quality of the
      segmentation using several volumetric and voxel by voxel measures. Our results
      show improved performance in terms of segmentation compared to state-of-the-art
      approaches, obtaining a mean overlap of 80.75%. Moreover, we present a
      quantitative volumetric analysis of caudate abnormalities in pediatric ADHD, the
      results of which show strong correlation with expert manual analysis. CONCLUSION:
      CaudateCut generates segmentation results that are comparable to gold-standard
      segmentations and which are reliable in the analysis of differentiating
      neuroanatomical abnormalities between healthy controls and pediatric ADHD.

PMID- 22141927
TI  - Bifunctional TaqII restriction endonuclease: redefining the prototype DNA
      recognition site and establishing the Fidelity Index for partial cleaving.
AB  - BACKGROUND: The TaqII enzyme is a member of the Thermus sp. enzyme family that we
      propounded previously within Type IIS restriction endonucleases, containing
      related thermophilic bifunctional endonucleases-methyltransferases from various
      Thermus sp.: TaqII, Tth111II, TthHB27I, TspGWI, TspDTI and TsoI. These enzymes
      show significant nucleotide and amino acid sequence similarities, a rare
      phenomenon among restriction endonucleases, along with similarities in
      biochemical properties, molecular size, DNA recognition sequences and cleavage
      sites. They also feature some characteristics of Types I and III. RESULTS: Barker
      et al. reported the Type IIS/IIC restriction endonuclease TaqII as recognizing
      two distinct cognate site variants (5'-GACCGA-3' and 5'-CACCCA-3') while cleaving
      11/9 nucleotides downstream. We used four independent methods, namely, shotgun
      cloning and sequencing, restriction pattern analysis, digestion of particular
      custom substrates and GeneScan analysis, to demonstrate that the recombinant
      enzyme recognizes only 5'-GACCGA-3' sites and cleaves 11/9 nucleotides
      downstream. We did not observe any 5'-CACCCA-3' cleavage under a variety of
      conditions and site arrangements tested. We also characterized the enzyme
      biochemically and established new digestion conditions optimal for practical
      enzyme applications. Finally, we developed and propose a new version of the
      Fidelity Index - the Fidelity Index for Partial Cleavage (FI-PC). CONCLUSIONS:
      The DNA recognition sequence of the bifunctional prototype TaqII endonuclease
      methyltransferase from Thermus aquaticus has been redefined as recognizing only
      5'-GACCGA-3' cognate sites. The reaction conditions (pH and salt concentrations)
      were designed either to minimize (pH = 8.0 and 10 mM ammonium sulphate) or to
      enhance star activity (pH = 6.0 and no salt). Redefinition of the recognition
      site and reaction conditions makes this prototype endonuclease a useful tool for
      DNA manipulation; as yet, this enzyme has no practical applications. The
      extension of the Fidelity Index will be helpful for DNA manipulation with enzymes
      only partially cleaving DNA.

PMID- 22142018
TI  - Inflammatory skin responses induced by icatibant injection are mast cell mediated
      and attenuated by H(1)-antihistamines.
AB  - Icatibant, a bradykinin-2 receptor antagonist, is administered by subcutaneous
      injection for the treatment of attacks of type I and type II hereditary
      angioedema. Following injection, patients feel transient pain followed by a short
      lived wheal and flare response at the injection site. We hypothesized that the
      icatibant-induced wheal and flare response follows histamine release from
      activated skin mast cells and would therefore be reduced by an H(1)
      antihistamine. Intradermal injection of 100 MUl of 100 MUg/ml histamine and 10
      mg/ml icatibant into the forearms of health volunteers caused wheal and flare
      responses of a similar magnitude which were reduced by cetirizine pretreatment by
      49% and 41% (histamine) and 35% and 41% (icatibant). Studies in vitro showed that
      icatibant at 1 * 10(-4) and 1 * 10(-5) M caused significant (P < 0.05) histamine
      release from isolated human cutaneous mast cells. In conclusion, icatibant
      induces histamine-mediated wheal and flare responses that may be reduced in
      severity by prophylactic administration of an H(1)-antihistamine.

PMID- 22142020
TI  - The effects of different doses of caffeine on endurance cycling time trial
      performance.
AB  - This study investigated the effects of two different doses of caffeine on
      endurance cycle time trial performance in male athletes. Using a randomised,
      placebo-controlled, double-blind crossover study design, sixteen well-trained and
      familiarised male cyclists (Mean +/- s: Age = 32.6 +/- 8.3 years; Body mass =
      78.5 +/- 6.0 kg; Height = 180.9 +/- 5.5 cm VO2(peak) = 60.4 +/- 4.1 ml x kg(-1) x
      min(-1)) completed three experimental trials, following training and dietary
      standardisation. Participants ingested either a placebo, or 3 or 6 mg x kg(-1)
      body mass of caffeine 90 min prior to completing a set amount of work equivalent
      to 75% of peak sustainable power output for 60 min. Exercise performance was
      significantly (P < 0.05) improved with both caffeine treatments as compared to
      placebo (4.2% with 3 mg x kg(-1) body mass and 2.9% with 6 mg x kg(-1) body
      mass). The difference between the two caffeine doses was not statistically
      significant (P = 0.24). Caffeine ingestion at either dose resulted in
      significantly higher heart rate values than the placebo conditions (P < 0.05),
      but no statistically significant treatment effects in ratings of perceived
      exertion (RPE) were observed (P = 0.39). A caffeine dose of 3 mg x kg(-1) body
      mass appears to improve cycling performance in well-trained and familiarised
      athletes. Doubling the dose to 6 mg x kg(-1) body mass does not confer any
      additional improvements in performance.

PMID- 22142021
TI  - Si/Ge double-layered nanotube array as a lithium ion battery anode.
AB  - Problems related to tremendous volume changes associated with cycling and the low
      electron conductivity and ion diffusivity of Si represent major obstacles to its
      use in high-capacity anodes for lithium ion batteries. We have developed a group
      IVA based nanotube heterostructure array, consisting of a high-capacity Si inner
      layer and a highly conductive Ge outer layer, to yield both favorable mechanics
      and kinetics in battery applications. This type of Si/Ge double-layered nanotube
      array electrode exhibits improved electrochemical performances over the analogous
      homogeneous Si system, including stable capacity retention (85% after 50 cycles)
      and doubled capacity at a 3C rate. These results stem from reduced maximum hoop
      strain in the nanotubes, supported by theoretical mechanics modeling, and lowered
      activation energy barrier for Li diffusion. This electrode technology creates
      opportunities in the development of group IVA nanotube heterostructures for next
      generation lithium ion batteries.

PMID- 22142022
TI  - Lack of association between CDH1 C-160A genetic polymorphism and gastric cancer
      risk among Asian population.

PMID- 22142023
TI  - Interleukin-4 -590T/C polymorphism influences the susceptibility to nonsmall cell
      lung cancer.
AB  - Lung cancer is the leading cause of cancer mortality worldwide. Nonsmall cell
      lung cancer (NSCLC) accounts for most of these cases. Interleukin 4 (IL-4) is a
      typical pleiotropic T helper 2 cytokine and plays crucial roles in tumor
      immunology. IL-4 gene -590T/C polymorphism has been shown to be associated with
      different autoimmune diseases and cancers. The present study evaluated the
      correlation between this polymorphism and the susceptibility to NSCLC in the
      Chinese population. The IL-4 variant -590T/C was detected by polymerase chain
      reaction-restriction fragment length polymorphism in 1072 NSCLC cases and 1126
      age-matched healthy controls. Data were analyzed using the Chi-square test.
      Results showed that frequencies of IL-4 -590 TC, CC genotype, and -590 C allele
      were significantly lower in patients with NSCLC than in healthy controls (odds
      ratio [OR]=0.77, 95% confidence interval [CI] 0.64-0.93, p=0.006; OR=0.54, 95% CI
      0.38-0.76, p=0.0004; and OR=0.72, 95% CI 0.62-0.83, p=1.1 * 10(-5),
      respectively). Our data suggest that the -590T/C polymorphism of the IL-4 gene is
      associated with a decreased susceptibility to NSCLC.

PMID- 22142025
TI  - Evidence for long-lived, optically generated quenchers of excitons in single
      walled carbon nanotubes.
AB  - The nonlinear dependence of near-infrared photoluminescence (PL) emission on
      excitation intensity has been measured for individual nanotubes representing six
      different (n,m) species. Significant deviations from linearity are observed for
      intensities as low as ~100 W/cm(2), and an approximate inverse correlation is
      found between nonlinearity and PL action cross section (brightness). A model in
      which all PL nonlinearity arises from exciton-exciton annihilation is
      insufficient to account for the experimental data using realistic parameters. It
      is proposed that additional nonlinear quenching arises from photoinduced
      quenching states or species with longer lifetimes than emissive excitons.
      Evidence is also found for metastable photogenerated PL quenchers with lifetimes
      up to 20 s.

PMID- 22142026
TI  - Iridium-catalyzed [2+2+2] cycloaddition of alpha,omega-diynes with isocyanates.
AB  - [Ir(cod)Cl](2)/BINAP was found to be an efficient catalyst for the [2+2+2]
      cycloaddition of alpha,omega-diynes with isocyanates to give 2-pyridones. A wide
      range of isocyanates can be used for this reaction. Both aliphatic and aromatic
      isocyanates smoothly reacted with alpha,omega-diynes to give 2-pyridones in high
      yields. Aliphatic isocyanates were more reactive than aromatic isocyanates. For
      aromatic isocyanates, the electronic properties of the substituents affected the
      reactivity: electron-donating substituents enhanced the reaction. The reaction of
      unsymmetrical alpha,omega-diynes possessing two different internal alkyne
      moieties with isocyanates was regiospecific and gave a single product. This
      regioselectivity could be explained by the reaction of iridacyclopentadiene with
      a nitrogen-carbon double bond. The regioselectivity of the reaction of malonate
      derived diyne was controlled by a steric effect, while that of the reaction of
      ester-tethered diyne was controlled by an electronic effect.
      [Ir(cod)Cl](2)/chiral diphosphine catalyst could be used for the enantioselective
      synthesis of C-N axially chiral 2-pyridone. The reaction of diyne 1a with o
      methoxyphenyl isocyanate (7a) gave C-N axially chiral 2-pyridone (R)-8aa in 78%
      yield with 94% ee.

PMID- 22142024
TI  - 17beta-Oestradiol inhibits doxorubicin-induced apoptosis via block of the volume
      sensitive Cl(-)  current in rabbit articular chondrocytes.
AB  - BACKGROUND AND PURPOSE Chondrocyte apoptosis contributes to disruption of
      cartilage integrity in osteoarthritis. Recent evidence suggested that the volume
      sensitive organic osmolyte/anion channel [volume-sensitive (outwardly rectifying)
      Cl(-)  current (I(Cl,vol) )] plays a functional role in the development of cell
      shrinkage associated with apoptosis (apoptotic volume decrease) in several cell
      types. In this study, we investigated the cellular effects of 17beta-oestradiol
      on doxorubicin-induced apoptotic responses in rabbit articular chondrocytes.
      EXPERIMENTAL APPROACH Whole-cell membrane currents and cross-sectional area were
      measured from chondrocytes using a patch-clamp method and microscopic cell
      imaging, respectively. Caspase-3/7 activity was assayed as an index of apoptosis.
      KEY RESULTS Addition of doxorubicin (1 uM) to isosmotic bath solution rapidly
      activated the Cl(-)  current with properties similar to those of I(Cl,vol)  in
      chondrocytes. Doxorubicin also gradually decreased the cross-sectional area of
      chondrocytes, followed by enhanced caspase-3/7 activity; both of these responses
      were totally abolished by the I(Cl,vol)  blocker DCPIB (20 uM). Pretreatment of
      chondrocytes with 17beta-oestradiol (1 nM) for short (approximately 10 min) and
      long (24 h) periods almost completely prevented the doxorubicin-induced
      activation of I(Cl,vol)  and subsequent elevation of caspase-3/7 activity. These
      effects of 17beta-oestradiol were significantly attenuated by the oestrogen
      receptor blocker ICI 182780 (10 uM), as well as the phosphatidyl inositol-3
      kinase (PI3K) inhibitors wortmannin (100 nM) and LY294002 (20 uM). Testosterone
      (10 nM) had no effect on the doxorubicin-induced Cl(-)  current. CONCLUSIONS AND
      IMPLICATIONS 17beta-Oestradiol prevents the doxorubicin-induced cell shrinkage
      mediated through activation of I(Cl,vol)  and subsequent induction of apoptosis
      signals, through a membrane receptor-dependent PI3K pathway in rabbit articular
      chondrocytes.

PMID- 22142027
TI  - Laparoscopic transperitoneal pyelolithotomy for management of staghorn renal
      calculi.
AB  - BACKGROUND: Recent developments in laparoscopic and retroperitoneoscopic
      techniques have modified the treatment of renal and ureteral stones. We present
      the efficacy and possible adverse complications of laparoscopic pyelolithotomy
      for the treatment of staghorn stones as an alternative to percutaneous
      nephrolithotomy (PCNL) in our single-surgeon series. PATIENTS AND METHODS:
      Thirteen patients (10 males and 3 females) underwent transperitoneal laparoscopic
      pyelolithotomy for removal of staghorn stones. Mean stone size was 5.1 cm (range,
      4-6.5 cm). All patients had large stones in the renal pelvis and several (more
      than two) calices with extrarenal pelvis. RESULTS: Mean operative time was 177
      minutes (range, 110-240 minutes), and the mean hospital stay was 4 days (range, 3
      7 days). Transfusion was not required in any patient, and open conversion did not
      happen. Overall success rate was 84.6% (11/13), and 2 patients had residual
      stones that were managed with extracorporeal shockwave lithotripsy. There were no
      major complications (bleeding, sepsis, bowel injury, or urinary leakage).
      CONCLUSION: The role of laparoscopic kidney stone surgery has not been defined
      well, but laparoscopic transperitoneal pyelolithotomy may be performed with
      proper results and negligible complications in skillful hands. It could be a
      suitable alternative to PCNL for the treatment of staghorn stones in selected
      cases.

PMID- 22142028
TI  - Multi-institutional analysis of robotic radical cystectomy for bladder cancer:
      perioperative outcomes and complications in 227 patients.
AB  - PURPOSE: Recently, some surgeons have begun to describe single-institution case
      series with less invasive surgical approaches to bladder cancer such as
      laparoscopic or robotic-assisted techniques. We report on a multi-institutional,
      multi-surgeon experience with robotic radical cystectomy with regard to operative
      and pathologic outcomes and complications to evaluate the feasibility and
      reproducibility of this technique in a large cohort of patients. SUBJECTS AND
      METHODS: Two hundred twenty-seven patients (178 males and 49 females) underwent a
      robotic cystectomy and urinary diversion at one of four institutions. Operative
      outcomes, pathological results, and complications of this combined case series
      are herein reported. RESULTS: Mean age of this cohort was 67.1 years (range, 33
      86 years) with a mean American Society of Anesthesiologists score of 2.7 (range,
      2-4). One hundred sixty-eight patients (74%) underwent ileal conduit diversion,
      58 (26%) underwent orthotopic ileal neobladder, and 1 patient (<1%) had no
      diversion (end-stage renal disease). The urinary diversion was performed
      extracorporeally in 97% cases, with 7 patients (3%) undergoing an intracorporeal
      diversion. Mean operating room time of all patients was 5.5 hours, and mean
      surgical blood loss was 256 mL. On surgical pathology, 120 (53%) patients had pT2
      or less disease, 35 (15%) had pT3/T4 disease, and 46 (20%) had N+ disease. The
      mean number of lymph nodes removed was 18 (range, 3-52). There was a positive
      surgical margin in 5 cases--all with pT3-4 disease. Mean time to discharge was
      5.5 days (median, 5 days), with 70% of patients discharged on postoperative day 5
      or sooner. Sixty-eight patients (30%) experienced complications, with 7% having
      Clavien grade 3 or higher. On multivariate analysis, decreased age and increased
      American Society of Anesthesiologists score were predictors of higher Clavien
      complication score, with younger patients more likely to undergo neoadjuvant
      chemotherapy prior to surgery. CONCLUSION: A multi-institutional experience with
      robotic radical cystectomy appears to demonstrate acceptable operative and
      pathologic outcomes, thus helping to validate the previously reported single
      institution case series. Ultimately, oncologic follow-up of these patients will
      remain as the most important measure of therapeutic success.

PMID- 22142029
TI  - Use of a SILS port in transanal endoscopic microsurgery in the setting of a
      community hospital.
AB  - Transanal endoscopic microsurgery (TEM) is a well-known technique for the removal
      of rectal lesions. This operation poses several advantages over traditional anal
      excision, which include better visibility of the rectum, more precise border
      excision, and a lower recurrence rate of benign and stage T1 malignant neoplasms.
      Introducing a SILSTM port (Covidien) into the anal canal (originally developed
      for single-incision laparoscopic surgery), instead of the TEM proctoscope, may
      further enhance the technique. We performed excisions of rectal lesions in 3
      patients using a SILS port in TEM. In all cases, it was easy to maintain the
      rectum insufflated, and the visibility was excellent. The rectal lesions were
      successfully resected without significant intraoperative complications.
      Postoperative recovery was uneventful in both cases. TEM with a SILS port is a
      promising technique that may provide several advantages over the traditional TEM,
      including cost-effectiveness, and can be easily implemented in the setting of a
      community hospital.

PMID- 22142030
TI  - Anti-platelet therapy and managing ulcer risk.
AB  - Low-dose aspirin (ASA) has emerged as one of the most important causes of peptic
      ulcer bleeding in developed countries. Among the risk factors of ASA-associated
      ulcer bleeding, Helicobacter pylori infection is one of the few that is
      treatable. Recent evidence showed that among patients with a history of ASA
      associated ulcer bleeding, the long-term incidence of recurrent bleeding with ASA
      use is low after eradication of H. pylori alone. Thus, test-and-treat H. pylori
      is a potentially useful strategy for ASA users with high ulcer risk. However, the
      risk of bleeding is further increased by combining other anti-platelet drugs
      (e.g. clopidogrel) with ASA in acute coronary syndromes and coronary stent
      placement. There is good evidence that co-therapy with a proton-pump inhibitor
      (PPI) reduces upper gastrointestinal bleeding with ASA alone or dual anti
      platelet therapy. Recently, several meta-analyses of observational studies found
      that concurrent use of PPI and clopidogrel was associated with increased risk of
      major adverse cardiovascular events. Overall, the evidence does not suggest a
      clinically important interaction between PPIs and clopidogrel. However, there is
      a subset of patients who have reduced conversion of clopidogrel to its active
      metabolites due to genetic polymorphism of hepatic P-450 (carriers of CYP2C19
      loss-of-function alleles). Since PPIs are also metabolized by similar hepatic
      enzymes, it is uncertain whether patients carrying CY2C19 loss-of-function
      alleles are susceptible to concomitant PPI use. In the future, management of
      patients on dual anti-platelet therapy needs to be individualized according to
      their thrombotic and bleeding risks.

PMID- 22142031
TI  - Detailed three-dimensional visualization of resilin in the exoskeleton of
      arthropods using confocal laser scanning microscopy.
AB  - Resilin is a rubber-like protein found in the exoskeleton of arthropods. It often
      contributes large proportions to the material of certain structures in movement
      systems. Accordingly, the knowledge of the presence and distribution of resilin
      is essential for the understanding of the functional morphology of these systems.
      Because of its specific autofluorescence, resilin can be effectively visualized
      using fluorescence microscopy. However, the respective excitation maximum is in
      the UV range, which is not covered by the lasers available in most of the modern
      commercial confocal laser scanning microscopes. The goal of this study was to
      test the potential of confocal laser scanning microscopy (CLSM) in combination
      with a 405 nm laser to visualize and analyse the presence and distribution of
      resilin in arthropod exoskeletons. The results clearly show that all resilin
      dominated structures, which were visualized successfully using wide-field
      fluorescence microscopy (WFM) and a 'classical' UV excitation, could also be
      visualized efficiently with the proposed CLSM method. Furthermore, with the
      application of additional laser lines CLSM turned out to be very appropriate for
      studying differences in the material composition within arthropod exoskeletons in
      great detail. As CLSM has several advantages over WFM with respect to detailed
      morphological imaging, the application of the proposed CLSM method may reveal new
      information about the micromorphology and material composition of resilin
      dominated exoskeleton structures leading to new insights into the functional
      morphology and biomechanics of arthropods.

PMID- 22142032
TI  - Is the pleth variability index a surrogate for pulse pressure variation in a
      pediatric population undergoing spine fusion?
AB  - OBJECTIVE: To compare simultaneous measurements of pulse pressure variation (PPV)
      and pleth variability index (PVI) in patients undergoing spinal fusion. AIMS: To
      determine if PVI can be used as a surrogate for PPV and also the influence of the
      prone position on these measurements. BACKGROUND: Spine fusion is an involved
      surgical procedure requiring attention to fluid administration. Dynamic indices
      for assessing fluid responsiveness like PPV have proven useful to guide fluid
      administration. Plethysmographic waveform variation like PVI is an appealing
      surrogate for measurements like PPV that require invasive arterial pressure
      measurement. Spine fusion patients are unique and the potential of either PPV or
      PVI to guide fluid therapy has not been studied. METHODS: Patients undergoing
      spine fusion for scoliosis were studied. In addition to the usual monitors
      including direct arterial pressure measurement, a multi-wavelength pulse co
      oximeter was applied to measure PVI. Paired measurements of PPV and PVI were
      obtained and limits of agreement determined using the method of Bland and Altman.
      PPV and PVI in prone and supine positions were compared by paired t-test.
      RESULTS: The bias between PVI and PPV measurements was -0.56% with 95% limits of
      agreement of +21.67% to -20.55%. There was no significant difference between the
      prone and supine measurements at the P = 0.05 level (Table 1). CONCLUSIONS: Our
      data indicate that PVI is not a surrogate for PPV. PVI measurements were not
      influenced by changing from the supine to prone position and therefore may prove
      useful for patients undergoing spine surgery.

PMID- 22142033
TI  - New multifunctional surfactants from natural phenolic acids.
AB  - Several new multifunctional molecules derived from natural sources such as amino
      acids and hydroxycinnamic acids were synthesized. They exhibit various activities
      such as emulsifying, UV-protecting, and radical scavenging, thereby conforming to
      the latest requirements for cosmetic ingredients. The synthesis comprises only a
      few steps: (i) the amino acid, the acid groups of which are protected by
      esterification, is coupled with ferulic or caffeic acid; (ii) the p-hydroxyl
      group of the cinnamic derivative reacts with dodecyl bromide in the presence of
      potassium carbonate (the resulting compounds are highly lipophilic and tested as
      water/oil (W/O) emulsifiers); (iii) these molecules, by deprotonating the acid
      groups of the amino acids, with successive salification, are more hydrophilic,
      with stronger O/W emulsifying properties. The new multifunctional surfactants
      might prove useful for the treatment of multiple skin conditions, including loss
      of cellular antioxidants, damage from free radicals, damage from UV, and others.

PMID- 22142034
TI  - Size-controlled dissolution of organic-coated silver nanoparticles.
AB  - The solubility of Ag NPs can affect their toxicity and persistence in the
      environment. We measured the solubility of organic-coated silver nanoparticles
      (Ag NPs) having particle diameters ranging from 5 to 80 nm that were synthesized
      using various methods, and with different organic polymer coatings including
      poly(vinylpyrrolidone) and gum arabic. The size and morphology of Ag NPs were
      characterized by transmission electron microscopy (TEM). X-ray absorption fine
      structure (XAFS) spectroscopy and synchrotron-based total X-ray scattering and
      pair distribution function (PDF) analysis were used to determine the local
      structure around Ag and evaluate changes in crystal lattice parameters and
      structure as a function of NP size. Ag NP solubility dispersed in 1 mM NaHCO(3)
      at pH 8 was found to be well correlated with particle size based on the
      distribution of measured TEM sizes as predicted by the modified Kelvin equation.
      Solubility of Ag NPs was not affected by the synthesis method and coating as much
      as by their size. Based on the modified Kelvin equation, the surface tension of
      Ag NPs was found to be ~1 J/m(2), which is expected for bulk fcc (face centered
      cubic) silver. Analysis of XAFS, X-ray scattering, and PDFs confirm that the
      lattice parameter, a, of the fcc crystal structure of Ag NPs did not change with
      particle size for Ag NPs as small as 6 nm, indicating the absence of lattice
      strain. These results are consistent with the finding that Ag NP solubility can
      be estimated based on TEM-derived particle size using the modified Kelvin
      equation for particles in the size range of 5-40 nm in diameter.

PMID- 22142035
TI  - Staphylococcus aureus leucocidin ED contributes to systemic infection by
      targeting neutrophils and promoting bacterial growth in vivo.
AB  - Bloodstream infection with Staphylococcus aureus is common and can be fatal.
      However, virulence factors that contribute to lethality in S. aureus bloodstream
      infection are poorly defined. We discovered that LukED, a commonly overlooked
      leucotoxin, is critical for S. aureus bloodstream infection in mice. We also
      determined that LukED promotes S. aureus replication in vivo by directly killing
      phagocytes recruited to sites of haematogenously seeded tissue. Furthermore, we
      established that murine neutrophils are the primary target of LukED, as the
      greater virulence of wild-type S. aureus compared with a lukED mutant was
      abrogated by depleting neutrophils. The in vivo toxicity of LukED towards murine
      phagocytes is unique among S. aureus leucotoxins, implying its crucial role in
      pathogenesis. Moreover, the tropism of LukED for murine phagocytes highlights the
      utility of murine models to study LukED pathobiology, including development and
      testing of strategies to inhibit toxin activity and control bacterial infection.

PMID- 22142036
TI  - Factors affecting the use of maternal health services in Madhya Pradesh state of
      India: a multilevel analysis.
AB  - BACKGROUND: Improving maternal health is one of the eight Millennium Development
      Goals. It is widely accepted that the use of maternal health services helps in
      reducing maternal morbidity and mortality. The utilization of maternal health
      services is a complex phenomenon and it is influenced by several factors.
      Therefore, the factors at different levels affecting the use of these services
      need to be clearly understood. The objective of this study was to estimate the
      effects of individual, community and district level characteristics on the
      utilisation of maternal health services with special reference to antenatal care
      (ANC), skilled attendance at delivery and postnatal care (PNC). METHODS: This
      study was designed as a cross sectional study. Data from 15,782 ever married
      women aged 15-49 years residing in Madhya Pradesh state of India who participated
      in the District Level Household and Facility Survey (DLHS-3) 2007-08 were used
      for this study. Multilevel logistic regression analysis was performed accounting
      for individual, community and district level factors associated with the use of
      maternal health care services. Type of residence at community level and ratio of
      primary health center to population and percent of tribal population in the
      district were included as district level variables in this study. RESULTS: The
      results of this study showed that 61.7% of the respondents used ANC at least once
      during their most recent pregnancy whereas only 37.4% women received PNC within
      two weeks of delivery. In the last delivery, 49.8% mothers were assisted by
      skilled personnel. There was considerable amount of variation in the use of
      maternal health services at community and district levels. About 40% and 14% of
      the total variance in the use of ANC, 29% and 8% of the total variance in the use
      of skilled attendance at delivery and 28% and 8.5% of the total variance in the
      use of PNC was attributable to differences across communities and districts,
      respectively. When controlled for individual, community and district level
      factors, the variances in the use of skilled attendance at delivery attributed to
      the differences across communities and districts were reduced to 15% and 4.3%
      respectively. There were only marginal reductions observed in the variance at
      community and district level for ANC and PNC use. The household socio-economic
      status and mother's education were the most important factors associated with the
      use of ANC and skilled attendance at delivery. The community level variable was
      only significant for ANC and skilled attendance at delivery but not for PNC. None
      of the district level variables used in this study were found to be influential
      factors for the use of maternal health services. CONCLUSIONS: We found sufficient
      amount of variations at community and district of residence on each of the three
      indicators of the use of maternal health services. For increasing the utilisation
      of these services in the state, in addition to individual-level, there is a
      strong need to identify and focus on community and district-level interventions.

PMID- 22142037
TI  - Polioviral receptor binding ligand: a novel and safe peptide drug carrier from
      polioviral capsid.
AB  - Cellular uptake enhancement of green fluorescent protein (GFP) into human colon
      adenocarcinoma (HT-29) and human mouth epidermal carcinoma (KB) cells by a
      segment of VP1-BC loop polioviral capsid (V), a polioviral receptor binding
      peptide and HIV-I transactivator of transcription (Tat) was evaluated. HT-29 and
      KB cells were incubated with various molar concentrations of GFP, V, and Tat
      mixtures. Both V and Tat showed potent enhancement of GFP uptake into HT-29 and
      KB cells. In HT-29 cells, the V-GFP, Tat-GFP, and V-Tat-GFP mixtures enhanced the
      GFP cellular uptake efficiency with the maximum of 3.98-, 4.59-, and 4.08-folds
      of GFP at 1:3, 1:1/6, and 1/6:1:1/6 molar ratios, respectively. For KB cells, the
      V-GFP, Tat-GFP, and V-Tat-GFP mixtures enhanced the GFP cellular uptake
      efficiency with the maximum of 4.05-, 5.09-, and 4.91-folds of GFP at 1:1/6, 1:1,
      and 1:1:1 molar ratios, respectively. Both V and V-GFP mixtures showed a lower
      cytotoxicity effect than Tat and Tat-GFP mixture. These studies demonstrated the
      potential of polioviral capsid, a polioviral receptor binding peptide as a novel,
      low cytotoxicity carrier for the development of peptide drugs delivery system.

PMID- 22142038
TI  - Age-dependent behavioral strategies in a visual search task in baboons (Papio
      papio) and their relation to inhibitory control.
AB  - A computerized visual search task was presented to 18 guinea baboons (Papio
      papio) ranging from 2.7 to 14.3 years of age. The task, inspired from Hick's
      (1952) task, required detection of a target among a variable number of
      distractors equidistant to a start button. The reaction times (RTs) and movement
      times both increased with the number of distractors expressed in bits of
      information. However, the slope of RT per bit function correlated positively with
      age, whereas a negative correlation was found for the movement time slopes. In
      Experiment 2, the same baboons were required to inhibit an ongoing manual
      pointing toward a target stimulus, to reengage in a new point as a consequence of
      a change in target location. Results revealed a more accurate performance in the
      adults, suggesting that differences in behavioral strategies in Experiment 1 can
      be accounted for by a greater inhibitory control of the adult participants.
      Implications of these results are discussed regarding the relation between
      attention, inhibitory control, and behavioral strategies in monkeys, and the
      general significance of RT slopes in visual search tasks.

PMID- 22142039
TI  - Do bantams (Gallus gallus domesticus) amodally complete partly occluded lines? An
      analysis of line classification performance.
AB  - Humans perceive a line touching an edge of a large rectangle longer than the
      reality. Kanizsa (1979) has suggested that this illusion occurs because we
      perceive that the line is partly "hidden" behind the rectangle and automatically
      completes it. We tested whether bantams (Gallus gallus domesticus) would
      experience this perceptual phenomenon using a line classification task on the
      touch monitor, which was used in our previous study with rhesus monkeys and
      pigeons (Fujita, 2001). We trained three bantams to classify six lengths of black
      target lines into two categories, "short" or "long," ignoring a gray rectangle
      (Experiment 1) or a gray area (i.e., a left or a right half of the monitor was
      filled with gray; Experiment 2) located at the same distance (8 pixels) from the
      target line. In the test, the gap between the line and the gray rectangle (or
      area) sometimes changed (0, 4, or 8 pixels; we labeled these stimuli as G0, G4,
      and G8 respectively). Both of the two successfully trained bantams showed an
      illusion for G0, but the direction of illusion was reversed; that is, they judged
      the line in G0 to be "shorter" than that in G4 and G8. Further analyses proved
      that neither the gaps between the target line and the gray rectangle nor the
      total widths of the stimuli could account for the bantams' responses. These
      results suggest that bantams do not complete the "occluded" portion even when
      identification of its shape is not required.

PMID- 22142040
TI  - Acoustic and perceptual categories of vocal elements in the warble song of
      budgerigars (Melopsittacus undulatus).
AB  - The warble songs of budgerigars (Melopsittacus undulatus) are composed of a
      number of complex, variable acoustic elements that are sung by male birds in
      intimate courtship contexts for periods lasting up to several minutes. If these
      variable acoustic elements can be assigned to distinct acoustic-perceptual
      categories, it provides the opportunity to explore whether birds are perceptually
      sensitive to the proportion or sequential combination of warble elements
      belonging to different categories. By the inspection of spectrograms and by
      listening to recordings, humans assigned the acoustic elements in budgerigar
      warble from several birds to eight broad, overlapping categories. A neural
      network program was developed and trained on these warble elements to simulate
      human categorization. The classification reliability between human raters and
      between human raters and the neural network classifier was better than 80% both
      within and across birds. Using operant conditioning and a psychophysical task,
      budgerigars were tested on large sets of these elements from different acoustic
      categories and different individuals. The birds consistently showed high
      discriminability for pairs of warble elements drawn from between acoustic
      categories and low discriminability for pairs drawn from within acoustic
      categories. With warble elements reliably assigned to different acoustic
      categories by humans and birds, it affords the opportunity to ask questions about
      the ordering of elements in natural warble streams and the perceptual
      significance of this ordering.

PMID- 22142041
TI  - Invasive fungal infections in renal transplant recipients.
AB  - Invasive fungal infections are a significant and often lethal problem in
      transplant patients. Infections caused by geographically limited endemic fungi
      are infrequent, and Aspergillus species, Mucorales species, Candida species, and
      Cryptococcus neoformans are the opportunistic fungi responsible for most such
      infections. The symptoms of systemic fungal infections are nonspecific,
      particularly in their early stages. The high rates of mortality and graft loss
      owing to fungal infections render early diagnosis and treatment imperative in
      immunosuppressed patients. Current methods for the diagnosis of systemic fungal
      infections include imaging procedures, endoscopic methods and biopsies,
      microscopic and culture techniques, antibody and antigen-based serologic testing,
      and the detection (via polymerase chain reaction) of fungal deoxyribonucleic acid
      in blood or bronchoalveolar lavage fluid, as well as the careful analysis of
      signs and symptoms. Antifungal therapy should be initiated early in patients with
      a suspected fungal infection (even before laboratory findings have confirmed that
      diagnosis) and should be administered with appropriate adjustment of
      immunosuppressive regimens. To manage fungal infections in patients with renal
      failure, optimizing the pharmacokinetics of antifungal drugs to reduce the risk
      of nephrotoxicity is crucial.

PMID- 22142042
TI  - Transient improvement of acquired hepatocerebral degeneration with parkinsonian
      symptoms after failed liver transplant: case report and literature review.
AB  - OBJECTIVES: Acquired (non-Wilsonian) hepato-cerebral degeneration is an
      infrequent neurologic disorder in patients with liver dysfunction and
      longstanding portal-systemic shunting. The clinical manifestations include
      dysarthria, ataxia, tremor, and cognitive dysfunction. Typically, patients with
      acquired hepatocerebral degeneration respond poorly to medical therapy as the
      underlying end-stage liver disease remains. Information regarding the effect of
      orthotopic liver transplant on acquired hepatocerebral degeneration, however, is
      limited and conflicting. MATERIALS AND METHODS: We conducted a review of
      literature via a PubMed search to summarize the effect of orthotopic liver
      transplant on acquired hepatocerebral degeneration. RESULTS: We present a 56-year
      old man with compensated hepatitis C cirrhosis who developed acquired
      hepatocerebral degeneration with Parkinsonian symptoms refractory to conventional
      Parkinson medical therapy. Orthotopic liver transplant led to marked clinical
      improvement of the acquired hepatocerebral degeneration. However, the patient
      developed recurrence of acquired hepatocerebral degeneration 6-week
      postorthotopic liver transplant as he developed graft failure from aggressive
      progressive hepatitis C recurrence. Our review found a heterogeneous group of
      case series, suggesting that the experience with orthotopic liver transplant is
      variable. CONCLUSIONS: Our experience demonstrates that orthotopic liver
      transplant may lead to resolution of acquired hepatocerebral degeneration;
      however, acquired hepatocerebral degeneration may return with recurrent liver
      disease. Future studies with long-term follow-up are needed.

PMID- 22142043
TI  - Importance of education in organ donation.
AB  - OBJECTIVES: Transplanting is the sole therapy for the majority of organ
      insufficiencies, but the lack of organ donation limits transplanting. We
      evaluated the effect of education about "Organ Donation and Transplantation" over
      the false beliefs of the participants. MATERIALS AND METHODS: This interventional
      study was performed in a military unit between January and March 2010. Data on
      organ donation and demographic characteristics were collected by a questionnaire.
      The researcher gave the lesson, and then collected the data by the same
      questionnaire 2 months later. RESULTS: The rate of volunteering for organ
      donation increased from 45.4% to 84.8% (P < .001). Rate of consent for organ
      donations by relatives increased from 41% to 80.3% (P < .001). Also, general
      knowledge about organ donation increased from 34.8% to 93.7% (P < .001). Wrong
      beliefs about organ donation disappeared after the education. The entire organ
      donation rate among the volunteer participants increased from 60% to 84% (P <
      .001). No significant relation was found between volunteering to donate organs,
      and education and economic status. CONCLUSIONS: Education could correct false
      information and might lead to higher organ donation rates. This education (which
      gave positive results in a military unit) could become widespread.

PMID- 22142044
TI  - Elderly renal transplant recipients and renal dysfunction: a risk factor for
      hyperuricemia.
AB  - OBJECTIVES: To date, limited data are currently available on posttransplant
      hyperuricemia in elderly renal transplant patients. MATERIALS AND METHODS: We
      conducted a retrospective study on 120 renal transplant patients aged >= 60 years
      old who received a kidney with at least a minimum time of 1 year after transplant
      between 2008 and 2011 in Iran. Hyperuricemia was defined if serum uric acid was
      >= 416.36 MUmol/L in men (7.0 mg/dL), and >= 356.88 MUmol/L in women (6 mg/dL)
      that persisted for at least 2 consecutive tests. Moderate-to-severe hyperuricemia
      also was defined as a serum uric acid of >= 475.84 MUmol/L (8.0 mg/dL) in both
      sexes. RESULTS: The majority of cases were men (66%) and only 9% received their
      grafts from deceased donors. The rate of deceased kidney transplant was higher in
      normouricemic patients. The prevalence of late posttransplant hyperuricemia was
      37.5% of patients (n=45). Moderate-to-severe hyperuricemia was seen in 21
      patients (17.5%). Although hyperuricemia was commonly observed in women than in
      men (43% in women vs 32% in men; P = .02), the rate of moderate-to-severe
      hyperuricemia was similar among both sexes (4.5% vs 4.3%; P = .9). Hyperuricemia
      frequently occurred in patients receiving kidney from a female donor (50% vs 29%;
      P = .005). In univariate analysis, a significant correlation was seen between
      serum uric acid and serum creatinine (r=0.5, P = .000). On multivariate
      regression, high serum creatinine was only a risk factor for posttransplant
      hyperuricemia in elderly kidney transplants (P = .000). CONCLUSIONS:
      Posttransplant hyperuricemia was a quite common among elderly aged kidney
      recipients. It was correlated with renal allograft impairment.

PMID- 22142045
TI  - Methodologies for anti-HLA antibody screening in patients awaiting kidney
      transplant: a comparative study.
AB  - OBJECTIVES: The relevance of anti-HLA antibodies in patients awaiting kidney
      transplants is well recognized. During the past 40 years, kidney transplant
      candidates have been tested for these antibodies, and the choice of the detection
      assay has become essential. Recently, the pioneer method, the complement
      dependent cytotoxicity, has been integrated but has not been replaced by more
      sensitive solid-phase assays, such as the enzyme-linked immunosorbent assay and
      the bead-based technology (ie, flow cytometry: FlowPRA, and FlowAnalyzer:
      Luminex). MATERIALS AND METHODS: We compared the sensitivity and antibody
      specificity of these 4 techniques for detecting panel-reactive antibodies in a
      population of 101 consecutive patients awaiting a renal transplant (which had
      already resulted positive in a prescreening analysis). RESULTS: Sera positive for
      class I and class II antibodies were 62 and 90 as assessed by the complement
      dependent cytotoxicity method, 76 and 58 by using enzyme-linked immunosorbent
      assay, 83 and 65 with Flow-panel-reactive antibodies, and 90 and 79 by Luminex.
      Luminex gave more positive scores than the others for class I HLA antibodies,
      whereas complement-dependent cytotoxicity revealed more positives for those of
      class II. CONCLUSIONS: Although Luminex appears more efficient among these
      assays, our results indicate that use of multiple methods is still the best
      approach for characterizing the immunologic status of these patients.

PMID- 22142046
TI  - Increased transcript levels of TNF-alpha, TGF-beta, and granzyme B in
      endomyocardial biopsies correlate with allograft rejection.
AB  - OBJECTIVES: Endomyocardial biopsies are the criterion standard in diagnosing
      acute cardiac transplant rejection. This study sought to analyze mRNA expression
      profiles of various immuneresponse-related genes in endomyocardial biopsies of
      heart transplant patients and to correlate the results with histologic findings.
      MATERIALS AND METHODS: Forty-three biopsies obtained from 6 heart transplant
      recipients experiencing acute rejection were analyzed for granzyme B, CTLA4, IL
      6, TGF-beta, and TNFa expression using real-time polymerase chain reaction. The
      results were compared with the histologic findings. Biopsies obtained before,
      during, and after acute rejection episodes were grouped according to the
      International Society of Heart and Lung Transplantation standard biopsy grading
      from 1990. Group 1 consisted of biopsies with International Society of Heart and
      Lung Transplantation grade 0 (n=12), group 2 of International Society of Heart
      and Lung Transplantation grade 1A (n=14), and group 3 of International Society of
      Heart and Lung Transplantation grades 1B, 2, 3A, and 4 (n=17). RESULTS: A strong
      correlation was seen between histologic groups and gene expression of granzyme B,
      which showed the highest overall transcript levels. CTLA4 was elevated in group
      2, but no further increase in the rejecting group 3 was seen. For IL-6, TGF-beta,
      and TNFa gene expression was strongly elevated in group 3 compared with groups 1
      and 2. On analysis of biopsies with International Society of Heart and Lung
      Transplantation, grade 0 and 1A, relative to the time point of rejection, we
      found a substantial increase in mRNA expression of all analyzed immune response
      related genes before a rejection episode. The strongest up-regulation was seen
      for granzyme B, TNFa, and TGF-beta. CONCLUSIONS: Our data suggest that analyses
      of gene expression provides valuable information in diagnosing heart transplant
      rejection. Furthermore, analyses of granzyme B, TGF-beta, and TNFa might not only
      confirm an ongoing rejection episode, but also may have a positive predictive
      value.

PMID- 22142047
TI  - External jugular venous pressure as an alternative to conventional central venous
      pressure in right lobe donor hepatectomies.
AB  - OBJECTIVES: Many centers have adopted central vein cannulation both for central
      venous pressure monitoring and fluid administration for right hepatectomy in
      living-liver donors. However, use of central venous catheters is associated with
      adverse events that are hazardous to patients and expensive to treat. This study
      sought to examine the use of external jugular venous pressure as an alternative
      to conventional central venous pressure in right lobe donor hepatectomies
      MATERIALS AND METHODS: Forty ASA grade I adult living liver-donors without a
      known history of significant cardiac or pulmonary diseases were enrolled in this
      prospective observational study. Paired measurement of venous pressures (external
      jugular venous pressure and internal jugular venous pressure) were taken at the
      following times: after induction of anesthesia, 30 minutes after skin incision,
      during right lobe mobilization (every 15 minutes), during hepatic transaction
      (every 15 minutes), after right lobe resection (every 15 minutes), and after
      abdominal closure. RESULTS: Paired measurements were equal in 47.5%, 53.5%,
      61.5%, 46.3%, and 52.5% for after induction, after skin incision, right lobe
      mobilization, right lobe transection, after resection, and before abdominal
      closure periods. However, all measurements were within acceptable limits of bias
      measurements (+/- 2 mm Hg). CONCLUSIONS: Central venous pressure catheter
      placement can be avoided and replaced by a less-invasive method such as external
      jugular venous pressure (which gave an acceptable estimate of central venous
      pressure in all phases of right lobe resection) in living-donor liver transplant
      and allowed equivalent monitor even during fluid restriction phases.

PMID- 22142048
TI  - Fungal infection in heart-lung transplant recipients receiving single-agent
      prophylaxis with itraconazole.
AB  - OBJECTIVES: Heart and lung transplant recipients are at risk for invasive fungal
      infections. This study evaluated the affect of single-agent antifungal
      prophylaxis with itraconazole on the rate of fungal infections after heart or
      lung transplant. MATERIALS AND METHODS: An observational, retrospective study was
      performed to evaluate the rate of fungal infections in heart and lung transplant
      recipients at the University of Kentucky Medical Center over 4.5 years who
      received itraconazole as a single therapy prophylaxis. RESULTS: Eighty-three
      recipients (42 heart, 41 lung) had an overall fungal infection incidence of 16.9%
      (14/83), while the incidence was 11.9% for heart recipients (5/42), and 22.0% for
      lung recipients (9/41). CONCLUSIONS: Single-agent use with itraconazole in heart
      or lung transplant recipients did not affect the rate of fungal infection as
      compared with previous reports. The incidence of fungal infection increased
      significantly within 3 months after escalation of immunosuppressant for treatment
      of acute rejection.

PMID- 22142049
TI  - Prevalence of viral infections and hemorrhagic cystitis in hematopoietic stem
      cell transplant recipients.
AB  - OBJECTIVES: About 7% to 70% of hemorrhagic cystitis is classified as early and
      late-onset incidence in hematopoietic stem cell transplant patients. The
      association between the prevalence of viral infections and hemorrhagic cystitis
      was evaluated in pretransplant and posttransplant recipients and donors.
      MATERIALS AND METHODS: Ethylenediaminetetra-acetic acid-treated blood and urine
      samples of 30 recipients and 24 donors were collected before hematopoietic stem
      cell transplant patients, and monitored for 100 days after transplant. Prevalence
      of BK virus DNA was investigated by polymerase chain reaction. Prevalence of
      adenovirus and cytomegalovirus DNA was evaluated by polymerase chain reaction.
      Type of transplant, conditioning regimens, graft-versus-host disease clinical
      grading, demographic data, hematologic, and biochemical indexes also were
      analyzed. RESULTS: Different grades of hematuria were found in 16 of 30 of the
      recipients with hemorrhagic cystitis. Severe hematuria and diffuse thickening of
      the bladder were found in 5 of 30 transplant patients. Multiple infections of BK
      virus, adenovirus, and cytomegalovirus were seen in 5 patients with severe
      hemorrhagic cystitis. The viruria of these viruses was decreased in patients with
      hemorrhagic cystitis as follows: BK virus (5 of 5), adenovirus (2 of 5), and
      cytomegalovirus (not detected). Also, a significant relation was found between
      hemorrhagic cystitis and risk factors including donor-recipient sex mismatches,
      familial relationships, leukemia as an underlying disease, older age, allogenic
      type of transplant, prophylactic and therapeutic dose of anti-graft-versus-host
      disease regimens. CONCLUSIONS: Detection of single and multiple infections of BK
      virus, adenovirus, and cytomegalovirus in blood and/or urine samples of
      hematopoietic stem cell transplant recipients, in combination with 1 or more
      inducing factors of hemorrhagic cystitis were enforced on the important role
      these risk factors play in the cause of hemorrhagic cystitis.

PMID- 22142050
TI  - Ramsay Hunt syndrome with atypical progress in a renal transplant recipient: a
      case report.
AB  - Ramsay Hunt syndrome is a rare complication of herpes zoster disease in which
      reactivation of latent varicella zoster virus infection occurs in the geniculate
      ganglion causing otalgia, unilateral vesicular eruption in a restricted
      dermatomal distribution, and peripheral facial paralysis. Dermal infections
      caused by human pathogenic herpes viruses are common in organ transplant
      recipients. For a transplant surgeon, it is imperative to remember that viral
      prophylaxis is essential in the follow-up of the transplant patients. Here, we
      presented a case of renal transplant and Ramsay Hunt syndrome with multiple
      cranial nerve involvement, with an atypical course. Management and differential
      diagnosis of this particular case are discussed with a review of the literature.

PMID- 22142051
TI  - Intraoperative hyperkaliemia complicating hand-assisted live-donor nephrectomy.
AB  - OBJECTIVES: Live donation has become increasingly valuable as a potential source
      of kidneys for transplant with hand-assisted laparoscopic donation is an
      important method of organ procurement. An important consideration is adequate
      preoperative and intraoperative planning, and precautions to minimize potential
      risks in the donor while providing a graft with good primary function. MATERIALS
      AND METHODS: We present a case of live donation in which a hand-assisted
      laparoscopic approach was used to facilitate kidney donation. The process was
      complicated by a period of profound intraoperative hyperkalaemia, subsequently
      ascribed to rhabdomyolysis owing to muscle necrosis. RESULTS: A 46-year-old man
      underwent assessment for live kidney donation for his brother. Preoperative
      investigations revealed normal renal function with no contraindications to
      donation. However, at the time of donation, a period of unexplained hyperkalaemia
      occurred that resolved spontaneously with fluid resuscitation and aggressive
      diuresis. After surgery, he was demonstrated to have an elevated creatine kinase
      level associated with unilateral gluteal pain and bruising. There were no long
      term complications, and the donor made a full recovery with normal renal
      function. Hyperkalaemia was ascribed to extensive rhabdomyolysis owing to
      positioning on the operating table at the time of surgery. CONCLUSIONS:
      Rhabdomyolysis associated with laparoscopic renal surgery requires prompt
      recognition and treatment while unexplained hyperkalaemia may herald its onset.
      It is important that an increased sense of vigilance is given to patients with
      increased muscularity or body mass, especially in donor nephrectomy patients,
      because of its effect on the remaining solitary kidney.

PMID- 22142052
TI  - Transitory peaked waveforms with elevated velocities in Doppler sonography after
      renal transplant.
AB  - Vascular complications after a renal transplant are rare and critical. Duplex
      Doppler evaluation constitutes the primary imaging modality in renal transplant.
      Early diagnosis and appropriate intervention to address potential complications
      are crucial in graft survival. This report describes a 25-year-old woman who
      underwent a live-donor renal transplant. During a routine study 4 hours after
      surgery, she was found to have high peak flow velocities suggestive of stenosis.
      An angiogram obtained as a result of this finding showed no abnormalities. A
      repeat duplex Doppler sonogram performed 12 hours later revealed normal waveforms
      and velocities. Postrenal transplant vascular complications are rare but may
      represent a significant morbidity factor for patients and grafts. Peak wave
      forms, elevated velocities, and a tardus-parvus configuration are suggestive of
      vascular disorders that require aggressive evaluation. In our patient, the
      Doppler ultrasound, angiogram, and lack of clinical signs were compatible with a
      renal artery vasospasm. This entity, despite its reversibility in the majority of
      instances, may cause severe graft injury if it does not regress promptly.

PMID- 22142053
TI  - Posttransplant lymphoproliferative disorder with lung involvement in a renal
      transplant recipient.
AB  - Posttransplant lymphoproliferative disorder is one of the most important
      complications of solid-organ transplant in terms of malignancy. Here, we report a
      case of Epstein-Barr-virus-negative posttransplant lymphoproliferative disorder
      of the T-cell type, involving the lung, in a renal transplant recipient. A 23
      year-old woman received a living-related renal transplant in 2002. She presented
      with a 6-month history of weight loss, malaise, night sweats, and lymphadenopathy
      6 years after the transplant. Chest radiograph showed miliary opacities. We
      performed a biopsy of the submandibular mass and computed-tomography-guided
      transthoracic needle biopsy of the lung. Pathological investigation of
      lymphadenopathy and lung were inconsistent with posttransplant
      lymphoproliferative disorder of T-cell type. After the diagnosis of
      posttransplant lymphoproliferative disorder, her immunosuppressive regimen was
      modified, and she was treated with cyclophosphamide, doxorubicin, vincristine,
      prednisolone, ifosfamide, carboplatin, and etoposide chemotherapies, which
      resulted in partial remission. Posttransplant lymphoproliferative disorders may
      be seen as an atypical presentation; the differential diagnosis should be thought
      of pulmonary infiltrates in renal transplant recipients.

PMID- 22142054
TI  - Bilateral lung transplant for bronchiectasis in asymmetric thorax: a case report.
AB  - Patients with suppurative lung diseases such as bronchiectasis and cystic
      fibrosis can be treated surgically, which leads to an asymmetric thorax, making
      lung transplant difficult in a volume-reduced hemithorax. We report a 52-year-old
      man with bronchiectasis and ventilation, dependent on a severe asymmetric thorax,
      who underwent bilateral lung transplant without cardiopulmonary bypass or
      extracorporeal membrane oxygenation support. This report suggests that bilateral
      lung transplant might be an efficient therapeutic option for such patients. Lung
      transplant is generally accepted as an effective way to deal with end-stage
      pulmonary diseases. Particularly, in patients with bronchiectasis or cystic
      fibrosis, single lung transplant may lead to infectious complications more
      easily. Thus, bilateral lung transplant is a better choice for such patients.
      However, some patients with bronchiectasis may have a history of surgical
      resection of target areas, which leads to an asymmetric thorax and makes lung
      transplant more difficult. We described 1 case of bilateral lung transplant for
      bronchiectasis in asymmetric thorax.

PMID- 22142055
TI  - Leukemia relapse after allogeneic bone marrow transplantation: how does chronic
      graft-versus-host disease influence the pattern and onset of relapse?
AB  - We describe a pattern of relapse in 601 patients who received an allogeneic
      hematopoietic stem cell transplant at our institution for acute or chronic
      leukemia and myelodysplasia over a period of 18 years. We show a correlation
      between chronic graft-versus-host disease and extramedullary relapse, suggesting
      that the expected graft versus leukemia effect in patients with chronic graft
      versus-host disease may preferentially maintain marrow remission without
      preventing relapse in extramedullary sites.

PMID- 22142056
TI  - Metabolic control and risk of hypoglycaemia during the first year of intensive
      insulin treatment in type 2 diabetes: systematic review and meta-analysis.
AB  - AIM: Aim of this study was to analyse clinical correlates of HbA1c, and of
      overall, nocturnal, and severe hypoglycaemia, through direct-weighted
      regressions, as well as the effect of different insulin regimens and insulin
      analogues, through meta-analysis. METHODS: Appropriate methodology (PRISMA
      statement) was used. Sixty-seven randomized studies, published as full papers
      were analysed to identify predictors of both HbA1c and hypoglycaemia; studies
      were included in a meta-analysis to study the effect of different insulin
      regimens or insulin analogues on HbA1c and hypoglycaemia during the first year of
      insulin treatment in type 2 diabetes patients. RESULTS: Final HbA1c, change of
      HbA1c, hypoglycaemia, nocturnal hypoglycaemia and severe hypoglycaemia were
      associated with intensity of treatment. Final HbA1c was higher with basal than
      with twice-a-day or prandial, and with twice-a-day than with prandial regimen,
      with opposite figures for hypoglycaemia. Within basal regimens, detemir and
      glargine were similar to NPH insulin on HbA1c, with less hypoglycaemia and
      nocturnal hypoglycaemia; within prandial regimens, new analogues were more
      effective than regular insulin on HbA1c, and induced less hypoglycaemia. The
      effect of glargine on HbA1c and on hypoglycaemia vanished with increasing number
      of insulin injections. CONCLUSION: Metabolic control and hypoglycaemia are
      associated with intensity of treatment. Basal regimens have a reduced effect on
      metabolic control, but are associated with lower frequency of hypoglycaemia.
      Newer analogues, short- and long-acting, yield better control and less
      hypoglycaemia than older analogues.

PMID- 22142140
TI  - Neighbourhood matters: perceptions of neighbourhood cohesiveness and associations
      with alcohol, cannabis and tobacco use.
AB  - INTRODUCTION AND AIMS: To examine relationships between perceived neighbourhood
      cohesion and alcohol, tobacco and cannabis consumption in New Zealand. DESIGN AND
      METHODS: A two-level random intercept regression model was used to examine the
      extent to which perception of neighbourhood cohesion (at the individual and area
      level) was associated with the frequency of substance (alcohol, tobacco and
      cannabis) consumption, after controlling for demographics and deprivation. This
      study is based on data from two national Health Behaviours Surveys (Drugs and
      Alcohol) conducted in 2003 and 2004 in New Zealand. Data were collected by
      computer-assisted telephone interviewing with two complementary computer-assisted
      cellphone interviewing samples. The combined sample consists of 6346 men and 8411
      women (n = 14,757) distributed across 1572 census area units. RESULTS: Perception
      of neighbourhood cohesion was significantly associated with the level of alcohol,
      tobacco and cannabis consumption. Individuals who perceived their neighbourhood
      as more cohesive had higher annual frequency of alcohol consumption but lower
      consumption on a typical drinking occasion. Higher perceived neighbourhood
      cohesion was also associated with a decrease in the probability of tobacco and
      cannabis use and of the amounts consumed. Area-level analysis suggested that
      aggregate census area unit-level neighbourhood cohesion exerted a significant
      additional contextual effect on the frequency of tobacco and cannabis consumption
      over and above individual perceptions of neighbourhood cohesiveness. DISCUSSION
      AND CONCLUSIONS: This study provides empirical evidence that perceptions of the
      neighbourhood social environment are associated with people's substance
      consumption patterns. Increasing residents' sense of neighbourhood cohesion might
      prove a promising way to decrease health-damaging consumption behaviours.

PMID- 22142141
TI  - Failure of innate and adaptive immune responses in controlling hepatitis C virus
      infection.
AB  - Effective innate and adaptive immune responses are essential for the control of
      hepatitis C virus (HCV) infection. Indeed, elimination of HCV during acute
      infection correlates with an early induction of innate and a delayed induction of
      adaptive immune responses. However, in the majority of acutely HCV-infected
      individuals, these responses are insufficient to clear the virus and persistence
      develops. In recent years, different mechanisms responsible for the failure of
      innate and adaptive immune responses have been identified. These include the
      proteolytic cleavage of molecules playing key roles in the induction of the
      interferon response, manipulation of interferon-induced effector proteins,
      interference with CD8+ T-cell function or immune escape in T- and B-cell
      epitopes. In this review, we discuss the possible roles of innate and adaptive
      immune responses in HCV clearance and the different evasion strategies used by
      the virus to escape these immune responses.

PMID- 22142142
TI  - Changes in hippocampal gene expression by 7-nitroindazole in rats submitted to
      forced swimming stress.
AB  - Nitric oxide (NO) is an atypical neurotransmitter that has been related to the
      pathophysiology of major depression disorder. Increased plasma NO levels have
      been reported in depressed and suicidal patients. Inhibition of neuronial nitric
      oxide synthase (nNOS), on the other hand, induces antidepressant effects in
      clinical and pre-clinical trials. The mechanisms responsible for the
      antidepressant-like effects of nNOS inhibitors, however, are not completely
      understood. In this study, genomic and proteomic analyses were used to
      investigate the effects of the preferential nNOS inhibitor 7-nitroindazole (7-NI)
      on changes in global gene and protein expression in the hippocampus of rats
      submitted to forced swimming test (FST). Chronic treatment (14 days, i.p.) with
      imipramine (15 mg/kg daily) or 7-NI (60 mg/kg daily) significantly reduced
      immobility in the FST. Saturation curves for Serial analysis of gene expression
      libraries showed that the hippocampus of animals submitted to FST presented a
      lower number of expressed genes compared to non-FST stressed groups. Imipramine,
      but not 7-NI, reverted this effect. GeneGo analyses revealed that genes related
      to oxidative phosphorylation, apoptosis and survival controlled by HTR1A
      signaling and cytoskeleton remodeling controlled by Rho GTPases were
      significantly changed by FST. 7-NI prevented this effect. In addition, 7-NI
      treatment changed the expression of genes related to transcription in the cAMP
      response element-binding pathway. Therefore, this study suggests that changes in
      oxidative stress and neuroplastic processes could be involved in the
      antidepressant-like effects induced by nNOS inhibition.

PMID- 22142143
TI  - Enhanced ambipolar charge injection with semiconducting polymer/carbon nanotube
      thin films for light-emitting transistors.
AB  - We investigate the influence of small amounts of semiconducting single-walled
      carbon nanotubes (SWNTs) dispersed in polyfluorenes such as poly(9,9-di-n
      octylfluorene-alt-benzothiadiazole (F8BT) and poly(9,9-dioctylfluorene) (F8) on
      device characteristics of bottom contact/top gate ambipolar light-emitting field
      effect transistors (LEFETs) based on these conjugated polymers. We find that the
      presence of SWNTs within the semiconducting layer at concentrations below the
      percolation limit significantly increases both hole and electron injection, even
      for a large band gap semiconductor like F8, without leading to significant
      luminescence quenching of the conjugated polymer. As a result of the reduced
      contact resistance and lower threshold voltages, larger ambipolar currents and
      thus brighter light emission are observed. We examine possible mechanisms of this
      effect such as energy level alignment, reduced bulk resistance above the
      contacts, and field-enhanced injection at the nanotube tips. The observed
      ambipolar injection improvement is applicable to most conjugated polymers in
      staggered transistor configurations or similar organic electronic devices where
      injection barriers are an issue.

PMID- 22142145
TI  - Emerging evidence for the role of genomic instability in male factor infertility.
AB  - Male infertility is a common and complex pathology affecting about 7% of men of
      reproductive age. Given its complexity, the underlying etiology for male
      infertility is often unknown. A growing amount of evidence suggests genomic
      instability may be an important factor in some cases of male factor infertility.
      While some specific manifestations of genomic instability, such as increased
      sperm aneuploidy rates and increased somatic translocations and inversions in
      infertile men, are well established, other facets of genomic instability
      associated with male infertility have not been thoroughly investigated. A limited
      body of recent work has identified a potential association between microsatellite
      instability and spermatogenic failure. In addition, mutations in mismatch repair
      and tumor suppressor genes, which could potentially lead to genomic instability,
      have been identified in some infertile men and animal models. In addition,
      results of two epidemiologic studies suggest spermatogenic defects might be just
      one aspect of a more systemic problem, possibly due to increased genomic
      instability. In this review we discuss well-established links between genomic
      instability and male infertility, as well as some of the emerging but less
      established data to support this relationship. We also propose some important
      areas of future research toward a more complete understanding of the underlying
      mechanisms for male infertility.

PMID- 22142144
TI  - The third extracellular loop of the human calcitonin receptor-like receptor is
      crucial for the activation of adrenomedullin signalling.
AB  - BACKGROUND AND PURPOSE: The extracellular loops (ECLs) in Family A GPCRs are
      important for ligand binding and receptor activation, but little is known about
      the function of Family B GPCR ECLs, especially ECL3. Calcitonin receptor-like
      receptor (CLR), a Family B GPCR, functions as a calcitonin gene-related peptide
      (CGRP) and an adrenomedullin (AM) receptor in association with three receptor
      activity-modifying proteins (RAMPs). Here, we examined the function of the ECL3
      of human CLR within the CGRP and AM receptors. EXPERIMENTAL APPROACH: A CLR ECL3
      chimera, in which the ECL3 of CLR was substituted with that of VPAC2 (a Family B
      GPCR that is unable to interact with RAMPs), and CLR ECL3 point mutants were
      constructed and transiently transfected into HEK-293 cells along with each RAMP.
      Cell-surface expression of each receptor complex was then measured by flow
      cytometry; [(125) I]-CGRP and [(125) I]-AM binding and intracellular cAMP
      accumulation were also measured. KEY RESULTS: Co-expression of the CLR ECL3
      chimera with RAMP2 or RAMP3 led to significant reductions in the induction of
      cAMP signalling by AM, but CGRP signalling was barely affected, despite normal
      cell-surface expression of the receptors and normal [(125) I]-AM binding. The
      chimera had significantly decreased AM, but not CGRP, responses in the presence
      of RAMP1. Not all CLR ECL3 mutants supported these findings. CONCLUSIONS AND
      IMPLICATIONS: The human CLR ECL3 is crucial for AM-induced cAMP responses via
      three CLR/RAMP heterodimers, and activation of these heterodimers probably relies
      on AM-induced conformational changes. This study provides a clue to the molecular
      basis of the activation of RAMP-based Family B GPCRs.

PMID- 22142146
TI  - Comparison of methods for calculating conditional expectations of sufficient
      statistics for continuous time Markov chains.
AB  - BACKGROUND: Continuous time Markov chains (CTMCs) is a widely used model for
      describing the evolution of DNA sequences on the nucleotide, amino acid or codon
      level. The sufficient statistics for CTMCs are the time spent in a state and the
      number of changes between any two states. In applications past evolutionary
      events (exact times and types of changes) are unaccessible and the past must be
      inferred from DNA sequence data observed in the present. RESULTS: We describe and
      implement three algorithms for computing linear combinations of expected values
      of the sufficient statistics, conditioned on the end-points of the chain, and
      compare their performance with respect to accuracy and running time. The first
      algorithm is based on an eigenvalue decomposition of the rate matrix (EVD), the
      second on uniformization (UNI), and the third on integrals of matrix exponentials
      (EXPM). The implementation in R of the algorithms is available at
      http://www.birc.au.dk/~paula/. CONCLUSIONS: We use two different models to
      analyze the accuracy and eight experiments to investigate the speed of the three
      algorithms. We find that they have similar accuracy and that EXPM is the slowest
      method. Furthermore we find that UNI is usually faster than EVD.

PMID- 22142147
TI  - Synergistic induction of periodontal tissue regeneration by binary application of
      human osteogenic protein-1 and human transforming growth factor-beta3 in Class II
      furcation defects of Papio ursinus.
AB  - BACKGROUND AND OBJECTIVE: Binary applications of recombinant human osteogenic
      protein-1 (hOP-1) and transforming growth factor-beta3 (hTGF-beta3) synergize to
      induce pronounced bone formation. To induce periodontal tissue regeneration,
      binary applications of hOP-1 and hTGF-beta(3) were implanted in Class II
      furcation defects of the Chacma baboon, Papio ursinus. MATERIAL AND METHODS:
      Defects were created bilaterally in the furcation of the first and second
      mandibular molars of three adult baboons. Single applications of 25 MUg hOP-1 and
      75 MUg hTGF-beta(3) in Matrigel((r)) matrix were compared with 20:1 binary
      applications, i.e. 25 MUg hOP-1 and 1.25 MUg hTGF-beta(3). Morcellated fragments
      of autogenous rectus abdominis striated muscle were added to binary applications.
      Sixty days after implantation, the animals were killed and the operated tissues
      harvested en bloc. Undecalcified sections were studied by light microscopy, and
      regenerated tissue was assessed by measuring volume and height of newly formed
      alveolar bone and cementum. RESULTS: The hOP-1 and hTGF-beta(3) induced
      periodontal tissue regeneration and cementogenesis. Qualitative morphological
      analysis of binary applications showed clear evidence for considerable
      periodontal tissue regeneration. Quantitatively, the differences in the
      histomorphometric values did not reach statistical significance for the group
      size chosen for this primate study. The addition of morcellated muscle fragments
      did not enhance tissue regeneration. Binary applications showed rapid expansion
      of the newly formed bone against the root surfaces following fibrovascular tissue
      induction in the centre of the treated defects. CONCLUSION: Binary applications
      of hOP-1 and hTGF-beta(3) in Matrigel((r)) matrix in Class II furcation defects
      of P. ursinus induced substantial periodontal tissue regeneration, which was
      tempered, however, by the anatomy of the furcation defect model, which does not
      allow for the rapid growth and expansion of the synergistic induction of bone
      formation, particularly when additionally treated with responding myoblastic stem
      cells.

PMID- 22142148
TI  - Physiological and biochemical metabolism of germinating broccoli seeds and
      sprouts.
AB  - Changes in physiological and biochemical metabolism as well as glucoraphanin and
      sulforaphane contents of germinating broccoli seeds and sprouts were investigated
      in this study. Sprout length, root length, and fresh weight increased with
      germination time. Dry weight varied from 2.5 to 3.0 mg per sprout. A rapid
      increase in respiratory rate of sprouts occurred between 24 and 36 h of
      germination and then stayed at a high level. HPLC analysis found that
      glucoraphanin content increased at the early stage (0-12 h) of germination,
      decreased to a low value of 3.02 mg/g at 48 h, and then reached the highest value
      of 6.30 mg/g at 72 h of germination. Sulforaphane content decreased dramatically
      during the first day of germination, then increased slowly, and reached a high
      value of 3.38 mg/g at 48 h before declining again.

PMID- 22142149
TI  - Synthesis of benzo-fused heterocycles by intramolecular alpha-arylation of ketone
      enolate anions.
AB  - A two-step synthesis of six-, seven-, eight-, and nine-member benzo-fused
      heterocycles in good to excellent yields is reported. The synthetic strategy
      involves the generation of a new intramolecular alpha-aryl ketone bond by the
      photostimulated S(RN)1 reaction of ketone enolate anions linked to a pendant
      haloarene as the key step. On the other hand, an intramolecular C(Ar)-C(Ar)
      coupling led to the formation of five- and six-member benzo-fused heterocycles
      (9H-carbazole and phenanthridine) when an aromatic amide anion is competitively
      formed.

PMID- 22142150
TI  - Search for poly(A) polymerase targets in E. coli reveals its implication in
      surveillance of Glu tRNA processing and degradation of stable RNAs.
AB  - Polyadenylation is a universal post-transcriptional modification involved in
      degradation and quality control of bacterial RNAs. In Escherichia coli, it is
      admitted that any accessible RNA 3' end can be tagged by a poly(A) tail for
      decay. However, we do not have yet an overall view of the population of
      polyadenylated molecules. The sampling of polyadenylated RNAs presented here
      demonstrates that rRNA fragments and tRNA precursors originating from the
      internal spacer regions of the rrn operons, in particular, rrnB are abundant
      poly(A) polymerase targets. Focused analysis showed that Glu tRNA precursors
      originating from the rrnB and rrnG transcripts exhibit long 3' trailers that are
      primarily removed by PNPase and to a lesser extent by RNase II and poly(A)
      polymerase. Moreover, 3' trimming by exoribonucleases precedes 5' end maturation
      by RNase P. Interestingly, characterization of RNA fragments that accumulate in a
      PNPase deficient strain showed that Glu tRNA precursors still harbouring the 5'
      leader can be degraded by a 3' to 5' quality control pathway involving poly(A)
      polymerase. This demonstrates that the surveillance of tRNA maturation described
      for a defective tRNA also applies to a wild-type tRNA.

PMID- 22142151
TI  - Flexibility of Markov modeling for clinical pharmacoeconomics: illustration for
      cost-effectiveness in early Parkinson's disease.

PMID- 22142152
TI  - Clinical pharmacology in neonates and young infants: the benefit of a population
      tailored approach.

PMID- 22142153
TI  - Macrocyclic antibiotics: a novel class of drug for the treatment of Clostridium
      difficile infection.

PMID- 22142155
TI  - Insulin to treat Alzheimer's disease: just follow your nose?
AB  - Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased
      expression of insulin and insulin receptor genes, and lower cerebrospinal insulin
      levels. Against this background, impaired brain insulin signaling may account for
      some of the cognitive deficits associated with this disease. Using the intranasal
      method, which effectively bypasses the blood-brain barrier to deliver and target
      insulin directly from the nose to the brain, a series of acute clinical trials
      involving healthy humans and AD patients have shown that increased CNS insulin
      action enhances learning and memory processes. This article summarizes and
      evaluates data from a recently published clinical trial, in which 4 months of
      intranasal insulin administration (20 IU insulin/day) preserved not only general
      cognition but also reduced the loss of metabolic integrity of the brain in adults
      with mild-to-moderate AD.

PMID- 22142156
TI  - Pharmacokinetic variability of anthelmintics: implications for the treatment of
      neurocysticercosis.
AB  - Human neurocysticercosis is a severe disease caused by the installation of Taenia
      solium larvae in the CNS. A wide variety of clinical manifestations are related
      to neurocysticercosis. These are determined by a number of important factors,
      including the number and location of the cysts, the stage of cystercerci and the
      host response to the infection. Epilepsy, focal neurological signs and increased
      intracranial pressure are the most common clinical manifestations of the disease.
      Neurocysticercosis is still deeply rooted in Latin America, Africa and Asia.
      Albendazole and praziquantel are the drugs used in the treatment of
      cysticercosis. Both drugs have limited solubility and extensive metabolism, and
      thus great interindividual variability in plasma levels is found. This article
      focuses on current knowledge of the pharmacokinetics and the drug interactions of
      the anthelmintic drugs and the perspectives in the treatment of this parasitic
      disease.

PMID- 22142157
TI  - Potential drug interactions associated with treatments for type 2 diabetes and
      its comorbidities: a clinical pharmacology review.
AB  - Type 2 diabetes is a disease of glucose metabolism that commonly involves
      multiple comorbidities, including lipid dyscrasias and hypertension. Each
      concurrent disorder contributes some risk of complications and requires
      therapeutic intervention. The simultaneous management of so many coexisting
      illnesses can be complex and commonly results in patients being prescribed
      multiple medications--referred to as polypharmacy--which may further complicate
      treatment. To ensure the best patient outcomes, the treating physician must be
      aware of all the therapeutic agents that a patient is taking to assess possible
      drug interactions that such a plethora of medications may confer. This article
      addresses the underlying comorbidites, the drugs commonly used to treat them and
      the interactions that may arise from concomitant administration.

PMID- 22142158
TI  - Is combination therapy an effective way of reaching lipid goals in type 2
      diabetes mellitus?
AB  - Type 2 diabetes mellitus is associated with a specific pattern of plasma lipid
      and lipoprotein abnormalities. Lipid goals are often not attained with statins
      alone, and combination lipid-lowering strategies may need to be considered in an
      attempt to further reduce the residual cardiovascular risk. Combination therapy
      utilizes various classes of lipid-lowering medications with different mechanisms
      of action and different effects on lipid levels. Clinical trial data support the
      efficacy of combining statins with fibrates, niacin, ezetimibe (cholesterol
      absorption inhibitor) and colesevelam (bile acid sequestrant) with the caveat
      that there are insufficient clinical trial data to show a further robust benefit
      on cardiovascular outcomes. Of the different combination therapy options to
      potentiate low-density lipoprotein cholesterol lowering in combination with a
      statin, colesevelam provides additional beneficial effects by further reducing
      hemoglobin A1c levels in Type 2 diabetes mellitus.

PMID- 22142159
TI  - Diabetic macular edema: new trends in management.
AB  - The treatment of diabetic macular edema may be evolving from a laser ablative
      approach into a pharmacotherapeutic approach. The exponential growth that has
      occurred over the past decade in the retinal pharmacotherapy field has led to the
      development of several pharmacotherapies for retinal vascular diseases such as
      diabetic macular edema. Many of these agents, in the form of intravitreal
      injections or sustained delivery devices, have already undergone clinical trial
      testing for safety and efficacy and many others are currently being similarly
      evaluated. Some of these agents have proven to be more efficacious than
      traditional laser therapy, and it is possible that traditional laser therapy for
      diabetic macular edema may be abandoned altogether in the near future, especially
      with the introduction of the micropulse laser. However, more research and
      experience is still needed in order to determine the best treatment agent or
      combination of therapeutic modalities, as well as the best treatment regimen for
      a given patient. In this article, we briefly review the major new developments in
      the field of diabetic macular edema treatment. In addition, we touch on some of
      the promising forthcoming therapies.

PMID- 22142160
TI  - Inflammation-mediated changes in drug transporter expression/activity:
      implications for therapeutic drug response.
AB  - Inflammation plays a critical role in host defense, maintaining cellular and
      tissue integrity following chemical, physical and biological insults.
      Inflammation presents in a variety of acute and chronic disease states and can
      contribute to disease resolution or progression depending upon the type,
      magnitude and duration of response. Importantly, it has been shown to modulate
      pharmacokinetic processes leading to variability in therapeutic drug response.
      Membrane-associated drug transporters are important determinants of drug
      disposition and pharmacokinetics and we, among others, have identified
      inflammation-mediated changes in their expression and regulation. Here, we
      discuss the current state of knowledge on drug transporter expression during
      acute and chronic inflammatory conditions and postulate how the altered
      expression of these transporters may modify the pharmacokinetics and
      pharmacodynamics of clinically important therapeutics. As understanding
      determinants of interpatient variability in therapeutic drug response is
      essential to the practice of medicine, this area of research warrants future
      clinical focus.

PMID- 22142161
TI  - Pimecrolimus 1% cream for the treatment of seborrheic dermatitis: a systematic
      review of randomized controlled trials.
AB  - Seborrheic dermatitis is a common, chronic, relapsing inflammatory skin disorder
      that manifests as erythema, scaling and pruritus in sebum gland-rich areas of the
      skin. The objective of this article is to evaluate the clinical efficacy of
      pimecrolimus 1% cream in the treatment of seborrheic dermatitis compared with
      corticosteroids, antimycotics, placebo or no intervention. Pimecrolimus 1% cream
      appears to be a well-tolerated and effective treatment for seborrheic dermatitis.
      It has comparable efficacy, in terms of decreasing severity of erythema, scaling
      and pruritus, to the standard treatments: topical corticosteroids and
      antimycotics. However, future studies with more standardized measures of
      treatment outcome are recommended. More studies may also be conducted to further
      evaluate pimecrolimus 1% cream as a long-term maintenance therapy for seborrheic
      dermatitis.

PMID- 22142163
TI  - Gene therapy for retinitis pigmentosa caused by MFRP mutations: human phenotype
      and preliminary proof of concept.
AB  - Autosomal recessive retinitis pigmentosa (RP), a heterogeneous group of
      degenerations of the retina, can be due to mutations in the MFRP (membrane-type
      frizzled-related protein) gene. A patient with RP with MFRP mutations, one of
      which is novel and the first splice site mutation reported, was characterized by
      noninvasive retinal and visual studies. The phenotype, albeit complex, suggested
      that this retinal degeneration may be a candidate for gene-based therapy. Proof
      of-concept studies were performed in the rd6 Mfrp mutant mouse model. The fast
      acting tyrosine-capsid mutant AAV8 (Y733F) vector containing the small chicken
      beta-actin promoter driving the wild-type mouse Mfrp gene was used. Subretinal
      vector delivery on postnatal day 14 prevented retinal degeneration. Treatment
      rescued rod and cone photoreceptors, as assessed by electroretinography and
      retinal histology at 2 months of age. This AAV-mediated gene delivery also
      resulted in robust MFRP expression predominantly in its normal location within
      the retinal pigment epithelium apical membrane and its microvilli. The clinical
      features of MFRP-RP and our preliminary data indicating a response to gene
      therapy in the rd6 mouse suggest that this form of RP is a potential target for
      gene-based therapy.

PMID- 22142164
TI  - Microenvironmental hypoxia orchestrating the cell stroma cross talk, tumor
      progression and antitumor response.
AB  - Hypoxia, a common feature of solid tumors and one of the hallmarks of tumor
      microenvironment, favors tumor survival and progression. Although hypoxia has
      been reported to play a major role in the acquisition of tumor resistance to cell
      death, the molecular mechanisms that control the survival of hypoxic cancer cells
      and the role of hypoxic stress in shaping the cross talk between immune cells and
      stroma components are not fully elucidated. Recently, several lines of
      investigation are pointing to yet another ominous outcome of hypoxia in the tumor
      microenvironment involving suppression of antitumor immune effector cells and
      enhancement of tumor escape from immune surveillance. Although the identification
      of tumor-associated antigens provided a new arsenal of approaches to enhance
      antigen-specific response, the immunotherapy approaches that are currently used
      in the clinic have only limited success. In fact, tumor stroma components
      including hypoxia are engaged in an active molecular cross talk that has serious
      implications for immunological recognition of tumor in shaping the
      microenvironment. In this review, we will focus on the impact of hypoxia on the
      regulation of the antitumor response and the subsequent tumor progression. We
      will also in particular discuss data that indicate that manipulation of hypoxic
      stress may represent an innovative strategy for a better immunotherapy of cancer.

PMID- 22142165
TI  - LPS-induced cytokine production in human monocytes and macrophages.
AB  - Lipopolysaccharide (LPS) from Gram-negative bacteria is one of the most potent
      innate immune-activating stimuli known. Here we review the current understanding
      of LPS effects on human monocyte and macrophage function. We provide an overview
      of LPS signal transduction with attention given to receptor cooperativity and
      species differences in LPS responses, as well as the role of tyrosine
      phosphorylation and lysine acetylation in signalling. We also review LPS
      regulated transcription, with emphasis on chromatin remodeling and primary versus
      secondary transcriptional control mechanisms. Finally, we review the regulation
      and function of LPS-inducible cytokines produced by human monocytes and
      macrophages including TNFalpha, the IL-1 family, IL-6, IL-8, the IL-10 family,
      the IL-12 family, IL-15 and TGFbeta.

PMID- 22142166
TI  - SWAP70 functions as a Rac/Rop guanine nucleotide-exchange factor in rice.
AB  - Rho family small GTPases are involved in diverse signaling processes including
      immunity, growth, and development. The activity of Rho GTPases is regulated by
      cycling between guanosine diphosphate (GDP)-bound inactive and guanosine
      triphosphate (GTP)-bound active forms, in which guanine nucleotide exchange
      factors (GEFs) predominantly function to promote activation of the GTPases. In
      animals, most Rho GEFs possess a Dbl (diffuse B-cell lymphoma) homology (DH)
      domain which functions as a GEF-catalytic domain. However, no proteins with the
      DH domain have been identified in plants so far. Instead, plant-specific Rho GEFs
      with the PRONE domain responsible for GEF activity have been found to constitute
      a large family in plants. In this study, we found rice homologs of human SWAP70,
      Oryza sativa (Os) SWAP70A and SWAP70B, containing the DH domain. OsSWAP70A
      interacted with rice Rho GTPase OsRac1, an important signaling factor for immune
      responses. The DH domain of OsSWAP70A exhibited the GEF-catalytic activity toward
      OsRac1 as found in animal Rho GEFs, indicating that plants have the functional DH
      domains. Transient expression of OsSWAP70A enhanced OsRac1-mediated production of
      reactive oxygen species in planta. Reduction of OsSWAP70A and OsSWAP70B mRNA
      levels by RNA interference resulted in the suppression of chitin elicitor-induced
      defense gene expression and ROS production. Thus, it is likely that OsSWAP70
      regulates immune responses through activation of OsRac1.

PMID- 22142167
TI  - Directing group-controlled hydrosilylation: regioselective functionalization of
      alkyne.
AB  - Pt(0)-catalyzed hydrosilylation of unsymmetric alkynes proceeds in a highly
      regioselective manner with a dimethylvinylsilyl (DMVS) group as the directing
      group. This hydrosilylation affords a single regioisomer of silylalkenes from
      propargylic and homopropargylic alcohol derivatives. DMVS also has an
      accelerating effect that allows group-selective hydrosilylation of the DMVS
      attached alkyne prior to that of other alkynes. Combined hydrosilylation and
      transformation reactions of the resulting silylalkenes afford various tri
      substituted alkenes and multi-oxy-functionalized compounds with high
      regioselectivity from unsymmetric alkynes.

PMID- 22142169
TI  - School-related assets and youth risk behaviors: alcohol consumption and sexual
      activity.
AB  - BACKGROUND: Two risk behaviors, alcohol consumption and early initiation of
      sexual intercourse (ISI), can have devastating consequences for youth. The
      purpose of this study was to determine the association of school connectedness
      and school-related behaviors (eg, academic performance, skipping school, getting
      into trouble at school) with these 2 risk behaviors. METHODS: The Youth Asset
      Survey (YAS) was administered to 1117 youth/parent pairs in their homes using
      Computer-Assisted Personal/Self-Interviewing (CAPI/CASI). The YAS measures 17
      youth assets and risk behaviors including alcohol consumption and sexual
      activity. RESULTS: The mean age of the sample was 14.3 years; 53% were female;
      and 70% were from 2-parent homes. Five school-related behaviors were positively
      associated with no ISI. Four school-related behaviors were positively associated
      with reporting no alcohol consumption in the past 30 days, including the School
      Connectedness asset (only among 12- to 13-year-olds), not skipping school (only
      among non-Hispanic Caucasians), staying out of trouble, and paying attention.
      CONCLUSIONS: School is very much a part of the lives of youth and therefore the
      relationship they have with their school experience is important and may
      influence their involvement in risk behaviors. Feeling connected to school is a
      positive asset that can protect youth from such risky behaviors as sexual
      initiation and alcohol consumption.

PMID- 22142170
TI  - Improving elementary school quality through the use of a social-emotional and
      character development program: a matched-pair, cluster-randomized, controlled
      trial in Hawai'i.
AB  - BACKGROUND: School safety and quality affect student learning and success. This
      study examined the effects of a comprehensive elementary school-wide social
      emotional and character education program, Positive Action, on teacher, parent,
      and student perceptions of school safety and quality utilizing a matched-pair,
      cluster-randomized, controlled design. The Positive Action Hawai'i trial included
      20 racially/ethnically diverse schools and was conducted from 2002-2003 through
      2005-2006. METHODS: School-level archival data, collected by the Hawai'i
      Department of Education, were used to examine program effects at 1-year post
      trial. Teacher, parent, and student data were analyzed to examine indicators of
      school quality such as student safety and well-being, involvement, and
      satisfaction, as well as overall school quality. Matched-paired t-tests were used
      for the primary analysis, and sensitivity analyses included permutation tests and
      random-intercept growth curve models. RESULTS: Analyses comparing change from
      baseline to 1-year post-trial revealed that intervention schools demonstrated
      significantly improved school quality compared to control schools, with 21%, 13%,
      and 16% better overall school quality scores as reported by teachers, parents,
      and students, respectively. Teacher, parent, and student reports on individual
      school-quality indicators showed improvement in student safety and well-being,
      involvement, satisfaction, quality student support, focused and sustained action,
      standards-based learning, professionalism and system capacity, and coordinated
      team work. Teacher reports also showed an improvement in the responsiveness of
      the system. CONCLUSIONS: School quality was substantially improved, providing
      evidence that a school-wide social-emotional and character education program can
      enhance school quality and facilitate whole-school change.

PMID- 22142171
TI  - Systematic review of social network analysis in adolescent cigarette smoking
      behavior.
AB  - BACKGROUND: Social networks are important in adolescent smoking behavior.
      Previous research indicates that peer context is a major causal factor of
      adolescent smoking behavior. To date, however, little is known about the
      influence of peer group structure on adolescent smoking behavior. METHODS:
      Studies that examined adolescent social networks with regard to their cigarette
      smoking behavior were identified through online and manual literature searches.
      Ten social network analysis studies involving a total of 28,263 adolescents were
      included in the final review. RESULTS: Of the 10 reviewed studies, 6 identify
      clique members, liaisons, and isolates as contributing factors to adolescent
      cigarette smoking. Significantly higher rates of smoking are noted among isolates
      than clique members or liaisons in terms of peer network structure. Eight of the
      reviewed studies indicate that peer selection or influence precedes adolescents'
      smoking behavior and intent to smoke. Such peer selection or influence accounts
      for a large portion of similarities among smoking adolescents. CONCLUSION:
      Adolescents who are identified as isolates are more likely to smoke and engage in
      risk-taking behaviors than others in the peer network structure. Given that the
      vast majority of current adult smokers started their smoking habits during
      adolescence, adolescent smoking prevention efforts will likely benefit from
      incorporating social network analytic approaches and focusing the efforts on
      isolates and other vulnerable adolescents from a peer selection and influence
      perspective.

PMID- 22142172
TI  - Adolescent health literacy: the importance of credible sources for online health
      information.
AB  - BACKGROUND: Little research has examined adolescent health literacy and its
      relationship with online health information sources. The purpose of this study is
      to explore health literacy among a predominantly Hispanic adolescent population
      and to investigate whether exposure to a credible source of online health
      information, MedlinePlus((r)), is associated with higher levels of health
      literacy. METHODS: An online survey was administered to a cross-sectional random
      sample of high school students in South Texas. Self-reported sociodemographic
      characteristics and data on health-information-seeking behavior and exposure to
      MedlinePlus((r)) were collected. Health literacy was assessed by eHEALS and the
      Newest Vital Sign (NVS). Linear and binary logistic regressions were completed.
      RESULTS: Of the 261 students who completed the survey, 56% had heard of
      MedlinePlus((r)), 52% had adequate levels of health literacy as measured by NVS,
      and the mean eHEALS score was 30.6 (possible range 8-40). Health literacy was
      positively associated with self-efficacy and seeking health information online.
      Exposure to MedlinePlus((r)) was associated with higher eHealth literacy scores
      (p < .001) and increased the likelihood of having adequate health literacy (odds
      ratio: 2.1; 95% CI: 1.1, 4.1). CONCLUSION: Exposure to a credible source of
      online health information is associated with higher levels of health literacy.
      The incorporation of a credible online health information resource into school
      health education curricula is a promising approach for promoting health literacy.

PMID- 22142173
TI  - Nutrition education intervention improves vegetable-related attitude, self
      efficacy, preference, and knowledge of fourth-grade students.
AB  - BACKGROUND: Impact of a classroom-based, standardized intervention to address
      limited vegetable consumption of fourth graders was assessed. METHODS: A 4
      lesson, vegetable-focused intervention, revised from extant materials was
      repurposed for Pennsylvania fourth graders with lessons aligned with state
      academic standards. A reliability-tested survey was modified, then examined for
      face and content validity and test-retest reliability. Lessons and evaluation
      materials were modified through an iterative testing process with educator
      feedback. A nonequivalent control group design was stratified by local
      Supplemental Nutrition Assistance Program Education (SNAP-Ed) partnering
      organizations with random assignment of participating elementary schools as
      control (N = 68) or intervention (N = 72) treatments. Independent t-tests
      compared control and intervention group changes. A mixed effects model was
      created to account for classroom effects from the nested sampling method of
      selecting classrooms within SNAP-Ed partnering organizations. General linear
      model univariate analyses of variance were conducted to assess intervention
      effects considering gender, and food preparation/cooking experience. RESULTS:
      During a 3- to 5-week time frame, 57 intervention classrooms (N = 1047 students)
      and 51 control classrooms (N = 890) completed pre- and post-testing. Intervention
      students improved in vegetable-related attitude, self-efficacy, preference, and
      knowledge scores (p < .001). For example, intervention vegetable preference
      increased 1.56 +/- 5.80 points; control group mean increase was only 0.08 +/-
      4.82 points. Group differences in score changes were not affected by gender or
      interactions between gender and food preparation/cooking experience with family.
      CONCLUSIONS: A defined intervention delivered in a SNAP-Ed setting can positively
      impact mediators associated with vegetable intake for fourth-grade students.

PMID- 22142174
TI  - Factors affecting sugar-sweetened beverage availability in competitive venues of
      US secondary schools.
AB  - BACKGROUND: This study explores sugar-sweetened beverage (SSB) availability in US
      secondary school competitive venues during the first 3 years following the school
      wellness policy requirement (2007-2009). Furthermore, analyses examine
      associations with school policy and SSB availability. METHODS: Analyses use
      questionnaire data from 757 middle and 762 high schools in the nationally
      representative Youth, Education, and Society study to examine soda and non-soda
      SSB availability associations with school policy including (1) beverage bottling
      contracts and related incentives, (2) individuals/organizations responsible for
      decisions regarding beverages available in vending machines, and (3) school
      wellness policies and nutrition guidelines. RESULTS: Non-soda SSBs made up the
      majority of SSBs in both middle and high schools. Soda was especially likely to
      be found in vending machines; non-soda SSBs were widely available across
      competitive venues. Access to soda decreased significantly over time; however,
      non-soda SSB access did not show a similar decrease. School policy allowing
      beverage supplier contractual involvement (bottling contract incentives and
      beverage supplier "say" in vending machine beverage choices) was related to
      increased SSB access. However, the existence of developed nutritional guidelines
      was associated with lower SSB availability. CONCLUSIONS: Students had high access
      to SSBs across competitive school venues, with non-soda SSBs making up the
      majority of SSB beverage options. Efforts to reduce access to SSBs in US
      secondary schools should include a focus on reducing both soda and non-soda SSBs,
      reducing beverage supplier involvement in school beverage choices, and
      encouraging the development of targeted nutritional guidelines for all
      competitive venues.

PMID- 22142175
TI  - Ethyl pyruvate promotes spinal cord repair by ameliorating the glial
      microenvironment.
AB  - BACKGROUND AND PURPOSE: Spinal cord injury (SCI) triggers a series of endogenous
      processes, including neuroinflammation and reactive astrogliosis, which may
      contribute to the failure of neural regeneration and functional recovery. In the
      present study, the effect of ethyl pyruvate on spinal cord repair was explored.
      EXPERIMENTAL APPROACH: Functional assessment and histological analyses of
      astrogliosis, neuroinflammation, neuronal survival and axonal regeneration were
      performed to investigate the effects of ethyl pyruvate (0.086, 0.215, 0.431 or
      0.646 mmol.kg(-1) .day(-1) ) on spinal cord repair in a rat model of SCI. The
      effect of ethyl pyruvate (5, 10 or 15 mM) on astrocytic activation was also
      evaluated in an in vitro'scratch-wound' model. KEY RESULTS: Functional assessment
      showed evident improvement of behavioural functions in the ethyl pyruvate-treated
      rats. Reactive astrogliosis was significantly inhibited in vivo, after injection
      of ethyl pyruvate (0.431 mmol.kg(-1) day(-1) ), and in vitro'scratch-wound' model
      in the presence of 10 or 15 mM ethyl pyruvate. The difference between effective
      concentration in vitro and in vivo suggests that the inhibitory effect of ethyl
      pyruvate on astrogliosis in damaged spinal cord is indirect. In addition, ethyl
      pyruvate (0.431 mmol.kg(-1) day(-1) ) attenuated SCI-induced neuroinflammation;
      it decreased the Iba-1-, ED-1- and CD11b-positive cells at the lesion site.
      Importantly, histological analyses showed a significantly greater number of
      surviving neurons and regenerative axons in the ethyl pyruvate-treated rats.
      CONCLUSIONS AND IMPLICATIONS: Ethyl pyruvate was shown to inhibit astrogliosis
      and neuroinflammation, promote neuron survival and neural regeneration, and
      improve the functional recovery of spinal cord, indicating a potential
      neuroprotective effect of ethyl pyruvate against SCI.

PMID- 22142176
TI  - Deletion of alpha-synuclein decreases impulsivity in mice.
AB  - The presynaptic protein alpha-synuclein, associated with Parkinson's Disease
      (PD), plays a role in dopaminergic neurotransmission and is implicated in impulse
      control disorders (ICDs) such as drug addiction. In this study we investigated a
      potential causal relationship between alpha-synuclein and impulsivity, by
      evaluating differences in motor impulsivity in the 5-choice serial reaction time
      task (5-CSRTT) in strains of mice that differ in the expression of the alpha
      synuclein gene. C57BL/6JOlaHsd mice differ from their C57BL/6J ancestors in
      possessing a chromosomal deletion resulting in the loss of two genes, snca,
      encoding alpha-synuclein, and mmrn1, encoding multimerin-1. C57BL/6J mice
      displayed higher impulsivity (more premature responding) than C57BL/6JOlaHsd mice
      when the pre-stimulus waiting interval was increased in the 5-CSRTT. In order to
      ensure that the reduced impulsivity was indeed related to snca, and not adjacent
      gene deletion, wild type (WT) and mice with targeted deletion of alpha-synuclein
      (KO) were tested in the 5-CSRTT. Similarly, WT mice were more impulsive than mice
      with targeted deletion of alpha-synuclein. Interrogation of our ongoing analysis
      of impulsivity in BXD recombinant inbred mouse lines revealed an association of
      impulsive responding with levels of alpha-synuclein expression in hippocampus.
      Expression of beta- and gamma-synuclein, members of the synuclein family that may
      substitute for alpha-synuclein following its deletion, revealed no differential
      compensations among the mouse strains. These findings suggest that alpha
      synuclein may contribute to impulsivity and potentially, to ICDs which arise in
      some PD patients treated with dopaminergic medication.

PMID- 22142177
TI  - Sperm structure and motility in the eusocial naked mole-rat, Heterocephalus
      glaber: a case of degenerative orthogenesis in the absence of sperm competition?
AB  - BACKGROUND: We have studied sperm structure and motility in a eusocial rodent
      where reproduction is typically restricted to a single male and behaviourally
      dominant queen. Males rarely compete for access to the queen during her estrus
      cycle, suggesting little or no role for sperm competition. RESULTS: Our results
      revealed an atypical mammalian sperm structure with spermatozoa from breeding,
      subordinate and disperser males being degenerate and almost completely lacking a
      "mammalian phylogenetic stamp". Sperm structure is characterized by extreme
      polymorphism with most spermatozoa classified as abnormal. Sperm head shapes
      include round, oval, elongated, lobed, asymmetrical and amorphous. At the
      ultrastructural level, the sperm head contains condensed to granular chromatin
      with large open spaces between the chromatin. Nuclear chromatin seems
      disorganized since chromatin condensation is irregular and extremely
      inconsistent. The acrosome forms a cap (ca 35%) over the anterior part of the
      head. A well defined nuclear fossa and neck with five minor sets of banded
      protein structures are present. The midpiece is poorly organized and contains
      only 5 to 7 round to oval mitochondria. The flagellar pattern is 9+9+2. A
      distinct degenerative feature of the tail principal piece is the absence of the
      fibrous sheath. Only 7% motile spermatozoa were observed which had exceptionally
      slow swimming speeds. CONCLUSION: In this species, sperm form has simplified and
      degenerated in many aspects and represents a specialised form of degenerative
      orthogenesis at the cellular level.

PMID- 22142178
TI  - Role of ghrelin on estrogen and progesterone secretion in the adult rat ovary
      during estrous cycle.
AB  - The objective of the present study was to evaluate the effects of ghrelin on the
      concentrations of estrogen (E(2)) and progesterone (P(4)) in serum and the mRNA
      expression of estrogen receptor beta (ER(beta)) and progesterone receptor
      (PR(A+B)) in ovary in rats during estrous cycle. Adult female Sprague Dawley rats
      were intracerebroventricularly (i.c.v.) injected with 3 nmol ghrelin during the
      estrous cycle, and sacrificed 15 min later. Blood samples and ovaries were
      collected. The concentrations of serum E(2) and P(4) were measured by
      radioimmunoassay, while the amount of ER(beta) and PR(A+B) mRNA was assessed by
      real-time quantitative PCR. Our studies showed that ghrelin could significantly
      reduce the serum concentration of E(2) throughout the estrous cycle (P < 0.05),
      the serum level of P(4) (P < 0.05), and the amount of ER(beta) mRNA during
      metestrus (P < 0.05). Meanwhile, the amount of PR(A+B) mRNA was only reduced
      during diestrus (P < 0.05). Overall, our present findings provide the first
      evidence that i.c.v. injection of ghrelin could reduce the serum concentration of
      E(2) and P(4) and the level of ER(beta) and PR(A+B) mRNA expression, supporting
      the role of ghrelin in reproduction.

PMID- 22142179
TI  - Nutrition support, quality of life and clinical outcomes.

PMID- 22142180
TI  - Anaerobic, nitrate-dependent oxidation of pyrite nanoparticles by Thiobacillus
      denitrificans.
AB  - Pyrite is a key mineral in the global biogeochemical cycles of sulfur and iron,
      yet its anaerobic microbial oxidation has eluded geochemists and microbiologists
      for decades. Recent reports indicated that anaerobic oxidation of pyrite is
      occurring, but the mechanism remains unclear. Here, we provide evidence for the
      capability of Thiobacillus denitrificans to anaerobically oxidize a putatively
      nanosized pyrite particle fraction with nitrate as electron acceptor. Nanosized
      pyrite was readily oxidized to ferric iron and sulfate with a rate of 10.1 MUM h(
      1). The mass balance of pyrite oxidation and nitrate reduction revealed a closed
      recovery of the electrons. This substantiates a further "missing lithotrophy" in
      the global cycles of sulfur and iron and emphasizes the high reactivity of
      nanominerals in the environment.

PMID- 22142181
TI  - Novel benzo-1,2,3-thiadiazole-7-carboxylate derivatives as plant activators and
      the development of their agricultural applications.
AB  - Plant activators are a novel kind of agrochemicals that could induce resistance
      in many plants against a broad spectrum of diseases. To date, only few plant
      activators have been commercialized. In order to develop novel plant activators,
      a series of benzo-1,2,3-thiadiazole-7-carboxylate derivatives were synthesized,
      and the structures were characterized by (1)H NMR, IR, elemental analyses, and
      HRMS or MS. Their potential systemic acquired resistance as plant activators was
      evaluated as well. Most of them showed good activity, especially, fluoro
      containing compounds 3d and 3e, which displayed excellent SAR-inducing activity
      against cucumber Erysiphe cichoracearum and Colletotrichum lagenarium in assay
      screening. Field test results illustrated that compounds 3d and 3e were more
      potent than the commercial plant activator, S-methyl benzo[1,2,3]thiadiazole-7
      carbothioate (BTH) toward these pathogens. Further, the preparation of compound
      3d is more facile than BTH with lower cost, which will be helpful for further
      applications in agricultural plant protection.

PMID- 22142182
TI  - Silver-mediated C-H activation: oxidative coupling/cyclization of N-arylimines
      and alkynes for the synthesis of quinolines.
AB  - A silver-mediated tandem protocol for the synthesis of quinolines involving the
      oxidative coupling/cyclization of N-arylimines and alkynes has been developed. We
      demonstrated that scenario-dependent metalation could occur either at the ortho C
      H bond of an N-arylimine through protonation-driven enhancement of acidity or at
      the terminal C-H bond of an alkyne by virtue of the carbophilic pi-acidity of
      silver. The diverse set of mechanistic manifolds implemented with a single type
      of experimental protocol points toward the importance of stringent reactivity
      analysis of each individual potentially reactive molecular site. Importantly, the
      direct arene C-H bond activation provides a unique and distinct mechanistic
      handle for the expansion of reactivity paradigms for silver. As expected, the
      protocol allows for the incorporation of both internal and terminal alkynes into
      the products, and in addition, both electron-withdrawing and -donating groups are
      tolerated on N-arylimines, thus enabling the vast expansion of substituent
      architectures on quinoline framework. Further, an intriguing phenomenon of
      structural isomerization and chemical bond cleavage has been observed for
      aliphatic internal alkynes.

PMID- 22142183
TI  - Emergency ultrasound-guided percutaneous embolization of post-traumatic bleeding
      hepatic artery pseudoaneurysms.
AB  - Hepatic artery pseudoaneurysm (HAP) is an uncommon but serious complication of
      blunt trauma abdomen which can be managed by non-surgical interventional methods.
      We describe the case of a young boy with blunt trauma abdomen having a large
      hepatic laceration associated with two pseudoaneurysms of the hepatic artery
      branches. Both these HAPs were successfully managed by percutaneous injection of
      cyanoacrylate glue under sonographic guidance. A major surgery was thus averted.
      A brief review of the etiology, diagnosis and management of HAP including the
      present case is discussed.

PMID- 22142184
TI  - Dissectometer - a new device for tensile strength testing of the vascular wall.
AB  - OBJECTIVES: The underlying mechanisms leading to aortic dissection are poorly
      understood. The present paper describes a unique device for aortic wall testing
      during open heart surgery which allows to directly predict the risk of aortic
      dissection. MATERIAL AND METHODS: Samples of the aortic wall were taken during
      surgery of the aortic valve and ascending aorta in 35 patients. Disruption of the
      samples was performed by using the dissectometer (patent pending). The output
      signal of the actuator was visualized by a "tensile strain curve". Seven
      destinctive curve parameters were compared by parametric or nonparametric
      evaluation with regard to the results of the normality test. RESULTS: Variations
      of all seven parameters in each patient differed not significantly; however,
      significant differences could be observed between the 35 patients. All parameters
      proved to be consistent and reproducible intra-individually. Histological
      analysis showed the integrity of the surface and localization of dissection in
      the external layer of tunica media. CONCLUSIONS: The dissectometer proved to be a
      suitable device to predict aortic wall consistence intraoperatively. Statistical
      analysis confirmed that a single sample of aorta is sufficient for assessment of
      aortic wall quality. A valid statistical discrimination between "healthy" and
      pathological aortas could only be assumed by generation of a large database of
      patients.

PMID- 22142185
TI  - A minimally invasive temporary cavernoso-saphenous shunt in the management of
      priapism after failed conservative treatment.
AB  - Priapism is an urological emergency with detrimental consequences, if not managed
      expeditiously. Though a rare condition with an incidence between 0.3 and 1.5 per
      100,000 population, its management options are limited and decision making could
      be challenging. We present a case of late presenting priapism for which the
      initial routine clinical care (aspiration, intracavernosal injection, and distal
      shunt) failed to relieve erection. Subsequently, the patient was successfully
      treated by a temporary cavernoso-saphenous shunt using carotid shunt and repeated
      heparin flushes. This novel surgical treatment offers an alternate method of
      relieving priapism, avoiding the long-term undesired effects associated with
      permanent proximal shunts such as cavernoso-venous grafts. Moreover, interval
      flushes (and/or repeated aspirations) with heparin ensures patency of this new
      shunt during the perioperative period. The patient recovered without any
      complications and the shunt was removed after one week. He has regained partial
      erection, however refused to have further treatment. Temporary cavernoso
      saphenous shunt using carotid shunt offers an alternate option of management of
      priapism in patients with failed initial conservative treatment and distal
      shunts.

PMID- 22142186
TI  - Is the face-perception system human-specific at birth?
AB  - The present study investigates the human-specificity of the orienting system that
      allows neonates to look preferentially at faces. Three experiments were carried
      out to determine whether the face-perception system that is present at birth is
      broad enough to include both human and nonhuman primate faces. The results
      demonstrate that the newborns did not show any spontaneous visual preference for
      the human face when presented simultaneously with a monkey face that shared the
      same features, configuration, and low-level perceptual properties (Experiment 1).
      The newborns were, however, able to discriminate between the 2 faces belonging to
      the 2 different species (Experiment 2). In Experiment 3, the newborns were found
      to prefer looking at an upright, compared with an inverted, monkey face, as they
      do for human faces. Overall, the results demonstrate that newborns perceive
      monkey and human faces in a similar way. These findings are consistent with the
      hypothesis that the system underlying face preference at birth is broad enough to
      bias newborns' attention toward both human and nonhuman primate faces.

PMID- 22142187
TI  - Language experiences and vocabulary development in Dominican and Mexican infants
      across the first 2 years.
AB  - We longitudinally investigated parental language context and infants' language
      experiences in relation to Dominican American and Mexican American infants'
      vocabularies. Mothers provided information on parental language context,
      comprising measures of parents' language background (i.e., childhood language)
      and current language use during interviews at infants' birth. Infants' language
      experiences were measured at ages 14 months and 2 years through mothers' reports
      of mothers' and fathers' engagement in English and Spanish literacy activities
      with infants and mothers' English and Spanish utterances during videotaped mother
      infant interactions. Infants' vocabulary development at 14 months and 2 years was
      examined using standardized vocabulary checklists in English and Spanish. Both
      parental language context and infants' language experiences predicted infants'
      vocabularies in each language at both ages. Furthermore, language experiences
      mediated associations between parental language context and infants'
      vocabularies. However, the specific mediation mechanisms varied by language.

PMID- 22142188
TI  - Ureteroscopy assisted retrograde nephrostomy: a new technique for percutaneous
      nephrolithotomy (PCNL).
AB  - Study Type - Therapy (case series). Level of Evidence 4. What's known on the
      subject? and What does the study add? Retrograde nephrostomy was first developed
      by Lawson et al. in 1983, and Hunter et al. reported 30 cases of retrograde
      nephrostomy in 1987. This procedure uses less radiation exposure and has a
      shorter duration compared with the previous percutaneous nephrostomy techniques.
      Retrograde nephrostomy using Lawson's procedure was reported in the late 1980s by
      several authors. But since then, few studies have been reported about this
      procedure due to the development of ultrasonography assisted percutaneous
      nephrostomy. With the arrival and development of the flexible ureteroscope (URS)
      both observation and manipulation in the renal pelvis are now easily achieved.
      The present procedure provides less radiation exposure, less bleeding, and a
      shorter procedure than previous percutaneous nephrostomy techniques. Using this
      procedure, after the needle has exited through the skin, no further steps are
      required in preparation for dilatation. In the present study, we continuously
      visualised from puncture to inserting the nephron-access sheath with the URS.
      OBJECTIVE: * To describe a technique for ureteroscopy assisted retrograde
      nephrostomy. PATIENTS AND METHODS: * Under general and epidural anaesthesia, the
      patient is placed in a modified-Valdivia position. Flexible ureteroscopy is
      carried out, and a Lawson retrograde nephrostomy puncture wire is placed in the
      ureteroscope (URS). * After the needle has exited through the skin, no further
      steps are required in preparation for dilatation. RESULTS: * After informed
      consent was obtained, two patients (a 43-year-old man with left renal stones and
      a 57-year-old woman with right renal stones) underwent this procedure. * The URS
      was positioned in the middle posterior calyx and punctured toward the skin.
      CONCLUSIONS: * This procedure involves less radiation exposure and shorter
      surgery than the previous percutaneous nephrostomy technique. * Our technique
      represents another new option for percutaneous nephrolithotomy in patients with a
      non-dilated intrarenal collecting system.

PMID- 22142190
TI  - SZ-117, a monoclonal antibody against matrix metalloproteinase-2 inhibits tumor
      cell-mediated angiogenesis.
AB  - In this study, using an in vitro tube formation model, we observed that SZ117, a
      monoclonal antibody against matrix metalloproteinase-2 (MMP2), attenuated a
      capillary-like tube structure formed by tumor endothelial cell 3B11 and human
      sarcoma cell MG63. In addition, gelatin zymography showed that SZ117 markedly
      inhibited MMP2 activity, but did not affect the capability of MMP9-mediated
      gelatin degradation. These data suggest that SZ117 might have an anti-tumor
      angiogenic effect and that angiogenic tumor cells and MMP2 may be targeted by
      monoclonal antibodies for novel anti-tumor angiogenic and anti-cancerous drug
      discovery.

PMID- 22142191
TI  - Mechanistic insights into LDL nanoparticle-mediated siRNA delivery.
AB  - Although small interfering RNA (siRNA) can silence the expression of disease
      related genes, delivery of these highly charged molecules is challenging.
      Delivery approaches for siRNAs are actively being pursued, and improved
      strategies are required for nontoxic and efficient delivery for gene knockdown.
      Low density lipoprotein (LDL) is a natural and endogenous nanoparticle that has a
      rich history as a delivery vehicle. Here, we examine purified LDL nanoparticles
      as carriers for siRNAs. When siRNA was covalently conjugated to cholesterol, over
      25 chol-siRNA could be incorporated onto each LDL without changing nanoparticle
      morphology. The resulting LDL-chol-siRNA nanoparticles were selectively taken up
      into cells via LDL receptor mediated endocytosis, resulting in enhanced gene
      silencing compared to free chol-siRNA (38% gene knock down versus 0% knock down
      at 100 nM). However, silencing efficiency was limited by the receptor-mediated
      entrapment of the LDL-chol-siRNA nanoparticles in endolysosomes. Photochemical
      internalization demonstrated that endolysosome disruption strategies
      significantly enhance LDL-mediated gene silencing (78% at 100 nM).

PMID- 22142192
TI  - Molecular characterization of heterochromatin proteins 1a and 1b from the
      silkworm, Bombyx mori.
AB  - Heterochromatin protein 1s (HP1s) are nonhistone chromosomal proteins that play a
      direct role in the formation and maintenance of heterochromatin structure.
      Similarly to Caenorhabditis elegans, silkworms possess holocentric chromosomes,
      in which diffused kinetochores extend along the length of each chromosome. We
      have isolated two silkworm HP1 homologues, BmHP1a and BmHP1b. Cytological
      analysis showed a unique localization of BmHP1s during cell division, in which
      these proteins first appear to dissociate from the chromosomes, but then return
      to enclose the chromosomes during metaphase. BmHP1s formed homo- and hetero
      dimers and interacted with BmSu(var)3-9, which is a methyltransferase for histone
      H3 lysine 9 (H3K9). We further showed, using a silkworm cell-based reporter
      system, that BmHP1b had higher transcriptional repression activity than BmHP1a,
      whereas BmHP1a interacted more strongly with BmSu(var)3-9 than did BmHP1b. These
      results suggest that silkworm HP1a and HP1b may play different roles in
      heterochromatin formation in holocentric silkworm chromosomes.

PMID- 22142195
TI  - Bilateral indolent epidermotropic CD8-positive lymphoid proliferations of the
      ear.

PMID- 22142193
TI  - Subtype selective NMDA receptor antagonists induce recovery of synapses lost
      following exposure to HIV-1 Tat.
AB  - BACKGROUND AND PURPOSE: Neurocognitive disorders afflict approximately 20% of HIV
      infected patients. HIV-1-infected cells in the brain shed viral proteins such as
      transactivator of transcription (Tat). Tat elicits cell death and synapse loss
      via processes initiated by NMDA receptor activation but mediated by separate
      downstream signalling pathways. Subunit selective NMDA receptor antagonists may
      differentially modulate survival relative to synaptic changes. EXPERIMENTAL
      APPROACH: Tat-evoked cell death was quantified by measuring propidium iodide
      uptake into rat hippocampal neurons in culture. The effects of Tat on synaptic
      changes were measured using an imaging-based assay that quantified clusters of
      the scaffolding protein postsynaptic density 95 fused to green fluorescent
      protein. KEY RESULTS: Dizocilpine, a non-competitive NMDA receptor antagonist,
      inhibited Tat-induced synapse loss, subsequent synapse recovery and Tat-induced
      cell death with comparable potencies. Memantine (10 uM) and ifenprodil (10 uM),
      which preferentially inhibit GluN2B-containing NMDA receptors, protected from Tat
      induced cell death with no effect on synapse loss. Surprisingly, memantine and
      ifenprodil induced synapse recovery in the presence of Tat. In contrast, the
      GluN2A-prefering antagonist TCN201 prevented synapse loss and recovery with no
      effect on cell death. CONCLUSIONS AND IMPLICATIONS: Synapse loss is a protective
      mechanism that enables the cell to cope with excess excitatory input. Thus,
      memantine and ifenprodil are promising neuroprotective drugs because they spare
      synaptic changes and promote survival. These GluN2B-preferring drugs induced
      recovery from Tat-evoked synapse loss, suggesting that synaptic pharmacology
      changed during the neurotoxic process. NMDA receptor subtypes differentially
      participate in the adaptation and death induced by excitotoxic insult.

PMID- 22142194
TI  - Secreted CXCL12 (SDF-1) forms dimers under physiological conditions.
AB  - Chemokine CXCL12 (CXC chemokine ligand 12) signalling through CXCR (CXC chemokine
      receptor) 4 and CXCR7 has essential functions in development and underlies
      diseases including cancer, atherosclerosis and autoimmunity. Chemokines may form
      homodimers that regulate receptor binding and signalling, but previous studies
      with synthetic CXCL12 have produced conflicting evidence for homodimerization. We
      used bioluminescence imaging with GL (Gaussia luciferase) fusions to investigate
      dimerization of CXCL12 secreted from mammalian cells. Using column chromatography
      and GL complementation, we established that CXCL12 was secreted from mammalian
      cells as both monomers and dimers. Secreted CXCL12 also formed homodimers in the
      extracellular space. Monomeric CXCL12 preferentially activated CXCR4 signalling
      through Galphai and Akt, whereas dimeric CXCL12 more effectively promoted
      recruitment of beta-arrestin 2 to CXCR4 and chemotaxis of CXCR4-expressing breast
      cancer cells. We also showed that CXCR7 preferentially sequestered monomeric
      CXCL12 from the extracellular space and had minimal effects on dimeric CXCL12 in
      cell-based assays and an orthotopic tumour xenograft model of human breast
      cancer. These studies establish that CXCL12 secreted from mammalian cells forms
      homodimers under physiological conditions. Since monomeric and dimeric CXCL12
      have distinct effects on cell signalling and function, our results have important
      implications for ongoing efforts to target CXCL12 pathways for therapy.

PMID- 22142196
TI  - Morphology transformation via pH-triggered self-assembly of peptides.
AB  - Three flexible peptides (P1: (C(17)H(35)CO-NH-GRGDG)(2)KG; P2: (Fmoc-GRGDG)(2)KG;
      P3: (CH(3)CO-NH-GRGDG)(2)KG) self-assembled to form a variety of morphologically
      distinct assemblies at different pHs. P1 formed nanofibers at pH 3, then self
      assembled into nanospheres with pH up to 6 and further changed to lamellar
      structures when the pH value was further increased to 10. P2 aggregated into an
      entwined network structure at pH 3, and then self-assembled into well-defined
      nanospheres, lamellar structures, and vesicles via adjusting the pH value.
      However, P3 did not self-assemble into well-ordered nanostructures, presumably
      due to the absence of a large hydrophobic group. The varying self-assembly
      behaviors of the peptides at different pHs are attributed to molecular
      conformational changes. These self-assembled supramolecular materials might
      contribute to the development of new peptide-based biomaterials.

PMID- 22142197
TI  - Non-monophyly and intricate morphological evolution within the avian family
      Cettiidae revealed by multilocus analysis of a taxonomically densely sampled
      dataset.
AB  - BACKGROUND: The avian family Cettiidae, including the genera Cettia, Urosphena,
      Tesia, Abroscopus and Tickellia and Orthotomus cucullatus, has recently been
      proposed based on analysis of a small number of loci and species. The close
      relationship of most of these taxa was unexpected, and called for a comprehensive
      study based on multiple loci and dense taxon sampling. In the present study, we
      infer the relationships of all except one of the species in this family using one
      mitochondrial and three nuclear loci. We use traditional gene tree methods
      (Bayesian inference, maximum likelihood bootstrapping, parsimony bootstrapping),
      as well as a recently developed Bayesian species tree approach (*BEAST) that
      accounts for lineage sorting processes that might produce discordance between
      gene trees. We also analyse mitochondrial DNA for a larger sample, comprising
      multiple individuals and a large number of subspecies of polytypic species.
      RESULTS: There are many topological incongruences among the single-locus trees,
      although none of these is strongly supported. The multi-locus tree inferred using
      concatenated sequences and the species tree agree well with each other, and are
      overall well resolved and well supported by the data. The main discrepancy
      between these trees concerns the most basal split. Both methods infer the genus
      Cettia to be highly non-monophyletic, as it is scattered across the entire family
      tree. Deep intraspecific divergences are revealed, and one or two species and one
      subspecies are inferred to be non-monophyletic (differences between methods).
      CONCLUSIONS: The molecular phylogeny presented here is strongly inconsistent with
      the traditional, morphology-based classification. The remarkably high degree of
      non-monophyly in the genus Cettia is likely to be one of the most extraordinary
      examples of misconceived relationships in an avian genus. The phylogeny suggests
      instances of parallel evolution, as well as highly unequal rates of morphological
      divergence in different lineages. This complex morphological evolution apparently
      misled earlier taxonomists. These results underscore the well-known but still
      often neglected problem of basing classifications on overall morphological
      similarity. Based on the molecular data, a revised taxonomy is proposed. Although
      the traditional and species tree methods inferred much the same tree in the
      present study, the assumption by species tree methods that all species are
      monophyletic is a limitation in these methods, as some currently recognized
      species might have more complex histories.

PMID- 22142198
TI  - Isoprene emission-free poplars--a chance to reduce the impact from poplar
      plantations on the atmosphere.
AB  - * Depending on the atmospheric composition, isoprene emissions from plants can
      have a severe impact on air quality and regional climate. For the plant itself,
      isoprene can enhance stress tolerance and also interfere with the attraction of
      herbivores and parasitoids. * Here, we tested the growth performance and fitness
      of Populus * canescens in which isoprene emission had been knocked down by RNA
      interference technology (PcISPS-RNAi plants) for two growing seasons under
      outdoor conditions. * Neither the growth nor biomass yield of the PcISPS-RNAi
      poplars was impaired, and they were even temporarily enhanced compared with
      control poplars. Modelling of the annual carbon balances revealed a reduced
      carbon loss of 2.2% of the total gross primary production by the absence of
      isoprene emission, and a 6.9% enhanced net growth of PcISPS-RNAi poplars.
      However, the knock down in isoprene emission resulted in reduced susceptibility
      to fungal infection, whereas the attractiveness for herbivores was enhanced. *
      The present study promises potential for the use of non- or low-isoprene-emitting
      poplars for more sustainable and environmentally friendly biomass production, as
      reducing isoprene emission will presumably have positive effects on regional
      climate and air quality.

PMID- 22142199
TI  - Identification of three novel polyphenolic compounds, origanine A-C, with unique
      skeleton from Origanum vulgare L. using the hyphenated LC-DAD-SPE-NMR/MS methods.
AB  - Identification of new compounds especially those with new skeletons from plant
      kingdom has long been a vital aspect for understanding phytochemistry, plant
      metabolisms and discovering new bioactive compounds. In this study, we identified
      and isolated three novel polyphenolic compounds, origanine A-C, from a well
      researched plant Origanum vulgare L. using the hyphenated LC-DAD-SPE-NMR/MS
      methods. Based on the combined information from UV-visible, accurate mass and 2D
      NMR spectra together with computational calculations, we found that these
      compounds all had a novel skeleton of cyclohexenetetracarboxylic acids attached
      with some well-known bioactive moieties including 3,4-dihydroxyphenyl, 4-(beta-d
      glucopyranosyloxy)benzyl alcohol (gastrodin), and 3-(3,4-dihydroxyphenyl)lactic
      acid (danshensu) residues. These findings provided crucial information to fill
      the gaps in our knowledge in terms of the plant secondary metabolism. This study
      also indicated the necessity for further research in plant secondary metabolism
      for even well-studied plants and demonstrated the powerfulness of the hyphenated
      LC-DAD-SPE-NMR/MS methods for comprehensive analysis of plant metabolites in
      particular for discovering new natural compounds.

PMID- 22142200
TI  - Admission heart rate as a predictor of mortality in patients with acute coronary
      syndromes.
AB  - INTRODUCTION: Heart rate (HR) is a prognostic factor in stable angina. However,
      in the context of acute coronary syndromes (ACS), it is less studied. AIMS: To
      evaluate the influence of admission HR as a prognostic factor in patients with
      ACS. METHODS: We evaluated in-hospital, 30-day and one-year mortality in patients
      with ACS, according to admission HR. RESULTS: We analysed 1126 patients, 69%
      males, mean age 64 years, 59% with ST-segment elevation acute myocardial
      infarction and 15% on medication with a beta-blocker. On admission, 14% presented
      signs of heart failure. In 10%, left ventricular ejection fraction was < 35%. In
      hospital mortality was 7.1%, 30-day mortality 9.1% and one-year mortality 10.7%.
      The best cut-off of HR to predict mortality was 80 bpm (sensitivity 64-66% and
      specificity 54-55%). By multivariate analysis, a heart rate >= 80 bpm was an
      independent predictor of all-cause mortality (HR 1.50, 95% CI: 1.01-2.23, P =
      0.047). CONCLUSIONS: In a population with ACS, a higher admission HR is an
      independent predictor of short- and medium-term prognosis, which is also
      independent of left ventricular function.

PMID- 22142201
TI  - Comparing the use of cobalt chromium stents to stainless steel stents in primary
      percutaneous coronary intervention for acute myocardial infarction: a prospective
      registry.
AB  - OBJECTIVES: To determine clinical outcome and rates of target vessel
      revascularization (TVR) in patients undergoing primary percutaneous coronary
      intervention (PCI) for STEMI who were treated with cobalt-chromium stents
      compared to stainless steel bare metal stents (BMS). BACKGROUND: The newer
      generation cobalt chromium stents were reported to achieve lower rates of TVR
      compared with conventional BMS. METHODS: Consecutive STEMI cases admitted within
      12 h of symptom onset and undergoing primary angioplasty and bare metal stent
      implantation 1 January 2002 and 31 December 2008 were identified. Primary
      outcomes were rates of clinically-driven TVR at six months as well as occurrence
      of major adverse cardiovascular events (MACE) either of all-cause death, repeat
      myocardial infarction or TVR at six months. RESULTS: 1030 cases with 1175 lesions
      (84% males) and median age of 58 years underwent primary PCI for STEMI in our
      registry. Overall procedural success rate was 98%. Stainless steel stents were
      inserted in 65% of the culprit lesions (stainless steel, n = 766 versus cobalt
      chromium, n = 264). Primary outcomes of TVR (3.5% in the stainless steel group
      and 3.4% in the cobalt chromium group, P = 0.93) and MACE (8.4% in the stainless
      steel group and 5.3% in the cobalt chromium group, P = 0.11) after six months
      were no different between the two groups. However, there were more deaths at 30
      days in the stainless steel group compared to the cobalt chromium group (3.5%
      versus 0.4%, HR 4.04 (1.03-3.88), P = 0.04). CONCLUSION: Both cobalt-chromium and
      stainless steel coronary stents were associated with similar and low risk of
      clinically-driven TVR.

PMID- 22142202
TI  - Energy transfer from systole to diastole: a novel device-based approach for the
      treatment of diastolic heart failure.
AB  - We hypothesized that attachment of elastic coil to the left ventricular (LV)
      wall, capable of exerting outward forces may allow the transfer of energy from
      systole to diastole and improve diastolic function. METHODS AND RESULTS: An extra
      ventricular-device, composed of a series of elastic elements interposed between
      spiral screws attached to the epimyocardium of the LV free-wall was developed.
      The hemodynamic and mechanical effects of the device were tested using a
      computerized model, an in vitro model utilizing a computerized-controlled fluid
      pump, eight healthy sheep and 10 mini-pigs induced with diastolic dysfunction by
      renal wrapping. The computerized and in vitro models predicted a reduction of the
      LV diastolic pressure curve and partial normalization of the pressure-volume
      loop. The sheep study demonstrated preservation of animal's wellbeing including
      maintaining cardiac mechanical function with stable energy transfer from systole
      to diastole throughout the 6 months follow-up. The mini-pigs study showed an
      increase in the early diastolic to systolic strain-rate ratio in the mid
      endocardial level (23 +/- 10%, P = 0.008) and an increase in early apical reverse
      rotation rate of 50% (P = 0.016 compared to control). CONCLUSIONS: This study
      presents a novel concept of using a mechanical device to transfer energy from
      systole to diastole, potentially enhancing diastolic function.

PMID- 22142203
TI  - Postpericardiotomy syndrome. Where is the catheter?

PMID- 22142204
TI  - Intravascular ultrasound virtual histology imaging in acute ST-elevation
      myocardial infarction: A useful clinical tool during primary percutaneous
      coronary intervention.
AB  - We described the novel use of intravascular ultrasound-virtual histology (IVUS
      VH) imaging in two young adult male patients who presented with acute inferior ST
      elevation myocardial infarction (STEMI) and we highlight the usefulness of this
      new invasive coronary imaging technique. Both patients had thrombotic occlusion
      of the right coronary arteries but the underlying pathophysiological mechanisms
      leading to acute thrombosis were different. The in vivo information obtained by
      IVUS-VH imaging was invaluable in pinpointing the likely etiology of STEMI and
      thus, guided our primary percutaneous coronary intervention strategy
      appropriately.

PMID- 22142205
TI  - Oxidative arylation of isochroman.
AB  - We report the use of a previously intractable nucleophile, anisole, in an
      oxidative "cross-dehydrogenative coupling" (CDC) reaction with the cyclic ether
      isochroman, as well as derivatives of both components. Metal catalysis was
      required for the reaction to proceed efficiently, and the reaction is highly
      sensitive to modification of either coupling partner but is able to produce a
      range of novel compounds via what is a synthetic alternative to the traditional
      oxa-Pictet-Spengler reaction.

PMID- 22142206
TI  - Development of lead source-specific exposure standards based on aggregate
      exposure assessment: Bayesian inversion from biomonitoring information to
      multipathway exposure.
AB  - Exposure of children to lead is of great concern, and the exposure standards for
      different media are important for protecting public safety. However, these media
      specific standards often fail to ensure the safety of children even when
      environmental lead levels are lower than the quality standards since humans are
      often exposed to lead via multiple pathways. To establish exposure standards to
      protect children from hazards associated with exposure to lead, an analytical
      tool for assessing aggregate exposure to lead based on Bayesian hierarchical
      model was developed, and then was used to update the external lead exposure of
      diet, paint, soil, air and drinking water using the blood lead levels in Chinese
      children aged 1-6 years. On the basis of updated external exposure, the source
      allocations for diet, paint, soil, air, and drinking water in China were 65.80 +/
      7.92%, 16.98 +/- 7.88%, 13.65 +/- 5.05%, 3.36 +/- 1.75%, and 0.20 +/- 0.14%,
      respectively. Based on the estimated source allocations, the exposure standards
      were evaluated to be 0.2 MUg/m(3), 24.25 mg/kg, 0.027 MUg/L, 0.051 MUg/mg, 0.042
      MUg/mg, 38.02 MUg/mg for air, soil, water, grains, vegetables, and paint,
      respectively. Since the standards setting procedure was based on the multipathway
      aggregate exposure assessment of lead, the newly proposed exposure standards
      should ensure the safety of children.

PMID- 22142208
TI  - The effects of valence and arousal on the emotional modulation of time
      perception: evidence for multiple stages of processing.
AB  - Previous research has demonstrated that both emotional valence and arousal can
      influence the subjective experience of time. The current research extends this
      work by (1) identifying how quickly this emotional modulation of time perception
      can occur and (2) examining whether valence and arousal have different effects at
      different stages of perception. These questions were addressed using a temporal
      bisection task. In each block of this task, participants are trained to
      distinguish between two different exposure durations. Participants are then shown
      stimuli presented at a number of durations that fall between the two learned
      times, and are asked to indicate whether the test stimulus was closer in duration
      to the shorter or longer learned item. In the current study, participants
      completed blocks of trials in which the durations were "Short" (100-300 ms) or
      "Long" (400-1600 ms). Stimuli consisted of neutral photographs as well as four
      categories of emotional images: high-arousal negative, high-arousal positive, low
      arousal negative, and low-arousal positive. In Short blocks, arousing and
      nonarousing negative images were judged to have been shown for shorter durations
      than they actually were (i.e., the duration was underestimated); this effect
      occurred at durations as brief as 133 ms. In Long blocks, the display time for
      highly arousing negative items was overestimated, whereas durations were
      underestimated for highly arousing positive items and less arousing negative
      items. These data suggest that arousal and valence have different effects at
      different stages of perception, possibly due to the different neural structures
      involved at each stage of the emotional modulation of time perception.

PMID- 22142207
TI  - Differential interference effects of negative emotional states on subsequent
      semantic and perceptual processing.
AB  - Past studies have revealed that encountering negative events interferes with
      cognitive processing of subsequent stimuli. The present study investigates
      whether negative events affect semantic and perceptual processing differently.
      Presentation of negative pictures produced slower reaction times than neutral or
      positive pictures in tasks that require semantic processing, such as natural or
      man-made judgments about drawings of objects, commonness judgments about objects,
      and categorical judgments about pairs of words. In contrast, negative picture
      presentation did not slow down judgments in subsequent perceptual processing
      (e.g., color judgments about words, size judgments about objects). The subjective
      arousal level of negative pictures did not modulate the interference effects on
      semantic or perceptual processing. These findings indicate that encountering
      negative emotional events interferes with semantic processing of subsequent
      stimuli more strongly than perceptual processing, and that not all types of
      subsequent cognitive processing are impaired by negative events.

PMID- 22142209
TI  - Love alters autonomic reactivity to emotions.
AB  - Periods of bond formation are accompanied by physiological and emotional changes,
      yet, little is known about the effects of falling in love on the individual's
      physiological response to emotions. We examined autonomic reactivity to the
      presentation of negative and positive films in 112 young adults, including 57
      singles and 55 new lovers who began a romantic relationship 2.5 months prior to
      the experiment Autonomic reactivity was measured by Respiratory Sinus Arrhythmia
      (RSA) to two baseline emotionally neutral films, two negative films, and two
      positive films. Results demonstrated that RSA in singles decreased during the
      presentation of negative emotions, indicating physiological stress response.
      However, no such decrease was found among new lovers, pointing to more optimal
      vagal regulation during the period of falling in love. Autonomic reactivity,
      indexed by RSA decrease from the positive to the negative films, was greater
      among singles as compared to lovers, suggesting that love buffers against
      autonomic stress and facilitates emotion regulation. Findings suggest that vagal
      regulation may be one mechanism through which love and attachment reduce stress
      and promote well-being and health.

PMID- 22142210
TI  - Feeling good: autonomic nervous system responding in five positive emotions.
AB  - Although dozens of studies have examined the autonomic nervous system (ANS)
      aspects of negative emotions, less is known about ANS responding in positive
      emotion. An evolutionary framework was used to define five positive emotions in
      terms of fitness-enhancing function, and to guide hypotheses regarding autonomic
      responding. In a repeated measures design, participants viewed sets of visual
      images eliciting these positive emotions (anticipatory enthusiasm, attachment
      love, nurturant love, amusement, and awe) plus an emotionally neutral state.
      Peripheral measures of sympathetic and vagal parasympathetic activation were
      assessed. Results indicated that the emotion conditions were characterized by
      qualitatively distinct profiles of autonomic activation, suggesting the existence
      of multiple, physiologically distinct positive emotions.

PMID- 22142211
TI  - The cost in remembering of ruminating on negative memories.
AB  - This study investigated retrieval mechanisms that may be involved in memory for
      distressing stimuli. Forty-one nonclinical participants watched a video clip
      depicting the immediate aftermath of a serious car accident. Following this, half
      of the participants were instructed to focus attention on the victims of the
      accident and to consider the negative sequelae of their injuries. The remaining
      participants were not given any instructions. Following the Victim Focus/Control
      period, all participants completed a cued-recall task assessing their memory of
      the video clip. Overall, victim-related details were better recalled than
      nonvictim related details. It is important to note that participants in the
      Victim Focus condition retrieved fewer peripheral details than participants in
      the Control condition. These results suggest that people focusing attention on
      distressing aspects of an event can experience a cost in remembering other
      aspects of the event. These findings may be interpreted in terms of enhanced
      recollection of central events or retrieval-induced forgetting mechanisms to
      explain patterns of diminished memory for aspects of distressing events.

PMID- 22142212
TI  - Gender moderates the relationship between emotion and perceived gaze.
AB  - Recent evidence shows that gender modulates the morphology of facial expressions
      and might thus alter the meaning of those expressions. Consequently, we
      hypothesized that gender would moderate the relationship between facial
      expressions and the perception of direct gaze. In Study 1, participants viewed
      male and female faces exhibiting joy, anger, fear, and neutral expressions
      displayed with direct and averted gazes. Perceptions of direct gaze were most
      likely for male faces expressing anger or joy and for female faces expressing
      joy. Study 2 established that these results were due to facial morphology and not
      to gender stereotypes. Thus, the morphology of male and female faces amplifies or
      constrains emotional signals and accordingly alters gaze perception.

PMID- 22142213
TI  - Self-esteem, self-affirmation, and schadenfreude.
AB  - In two studies we demonstrated that self-esteem has a negative relationship with
      schadenfreude toward a high achiever and that this relationship was mediated by
      the self-threat evoked by this high achiever. Moreover, we showed that this
      indirect relationship was contingent on an opportunity to affirm the self. When
      no self-affirmation opportunity was available, low self-esteem participants
      experienced a stronger self-threat when confronted with a high achiever, and this
      self-threat increased their schadenfreude, whereas this response was attenuated
      when they were given an opportunity to self-affirm. These findings indicate that
      the misfortunes of others can evoke schadenfreude because they provide people
      with an opportunity to protect or enhance their self-views.

PMID- 22142214
TI  - Context-dependent activation of reduced autobiographical memory specificity as an
      avoidant coping style.
AB  - According to the affect-regulation hypothesis (Williams et al., 2007), reduced
      autobiographical memory specificity (rAMS) or overgeneral memory (OGM) might be
      considered a cognitive avoidance strategy; that is, people learn to avoid the
      emotionally painful consequences associated with the retrieval of specific
      negative memories. Based on this hypothesis, one would predict significant
      negative associations between AMS and avoidant coping. However, studies
      investigating this prediction have led to equivocal results. In the present study
      we tested a possible explanation for these contradictory findings. It was
      hypothesized that rAMS (in part) reflects an avoidant coping strategy, which
      might only become apparent under certain conditions, that is, conditions that
      signal the possibility of 'danger.' To test this hypothesis, we assessed AMS and
      behavioral avoidance but experimentally manipulated the instructions. In the
      neutral condition, two parallel versions of the Autobiographical Memory Test
      (AMT) were presented under neutral instructions. In the threat condition, the
      first AMT was presented under neutral instructions, while the second AMT was
      presented under 'threat instructions.' Results showed no significant correlations
      between avoidance and OGM under neutral conditions but significant and markedly
      stronger correlations under threat conditions, with more avoidance being
      associated with fewer specific and more categoric memories. In addition, high
      avoiders showed a stronger reduction in AMS in the threat condition as compared
      with the neutral condition, while low avoiders showed no such difference between
      conditions. The data confirm that OGM can be considered as part of a broader
      avoidant coping style. However, more importantly, they show that, at least in
      nonclinical individuals, the activation of this coping style may depend on the
      context.

PMID- 22142215
TI  - Laparoscopic anatrophic nephrolithotomy: developments of the technique in the era
      of minimally invasive surgery.
AB  - BACKGROUND AND PURPOSE: The complete removal of the stone is the ultimate goal in
      management, a result that might not be attained even after several sessions of
      percutaneous nephrolithotomy (PCNL) and/or extracorporeal shockwave lithotripsy
      (SWL) and/or retrograde intrarenal surgery (ureteroscopy). The objective of this
      study is to assess our technique of anatrophic nephrolithotomy, with decreased
      renal ischemia and reduced patient morbidity. PATIENTS AND METHODS: From 2007 to
      2010, we performed eight anatrophic laparoscopic nephrolithotomies in adult
      patients with staghorn renal calculus. The mean patient age was 49 years (range
      35-62 y). The mean stone size was 53 mm (range 35-70 mm). All patients had
      complex renal calculi, with stones occupying more than 80% of the caliceal
      system. In all cases, a Double-J stent was placed before surgery. After clamping
      the hilum, the incision was made laterally and longitudinally through full
      thickness of cortex using a laparoscopic scalpel. A running cortical suture was
      performed with Hem-o-lok reinforcement. Renal function was assessed in three
      patients, using renography with technetium-99m-diethylenetriaminepentacetic acid
      (99mTc-DTPA), before and 3 months after the surgery. RESULTS: Procedures for all
      patients were completed laparoscopically. The mean operative time was 142.5
      minutes, and the mean warm ischemia time was 20.8 minutes. The estimated blood
      loss was 315 mL. The hospital stay average was 3.5 days. Only one patient had a
      complication--a vascular fistula with permanent postoperative hematuria. This
      patient subsequently underwent successful endovascular embolization. Residual
      stones were identified in 37% of cases (three patients) during follow-up imaging
      at 15 days. There were minimal changes on serum creatinine values. CONCLUSIONS:
      Laparoscopic surgery is feasible when anatrophic nephrolithotomy is indicated.
      This technique minimizes the barriers of an open flank incision, while achieving
      excellent stone-free rates. This minimally invasive technique should be
      considered for complex stones that would necessitate multiple renal access tracks
      and secondary procedures.

PMID- 22142216
TI  - Neonatal assessments for the preterm infant up to 4 months corrected age: a
      systematic review.
AB  - AIM: The aim of this study was to systematically review the clinimetric
      properties of longitudinal neonatal neurobehavioural and neuromotor assessments
      for preterm infants. METHOD: Twenty-seven assessment measures were identified.
      The following eight measures met the study inclusion criteria: Assessment of
      Preterm Infants' Behaviour (APIB), Neonatal Intensive Care Unit Network
      Neurobehavioural Scale (NNNS), Test of Infant Motor Performance (TIMP), Prechtl's
      Assessment of General Movements (GMs), Neurobehavioural Assessment of the Preterm
      Infant (NAPI), Dubowitz Neurological Assessment of the Preterm and Full-term
      Infant (Dubowitz), Neuromotor Behavioural Assessment (NMBA), and the Brazelton
      Neonatal Behavioural Assessment Scale (NBAS). The primary purposes included
      prediction (TIMP, GMs, Dubowitz), discrimination (all assessments), and
      evaluation of change (TIMP, NAPI). Measures of assessment were included in the
      study if they were (1) primarily neurobehavioural or neuromotor assessments that
      were suitable for use with preterm infants (<37 weeks gestation) up to 4 months
      corrected age and were discriminative, predictive, or evaluative; (2)
      standardized procedures designed for serial/longitudinal use; or (3) criterion or
      norm referenced. However, all assessment tools that were not published in English
      in a peer-reviewed journal or were primarily neurological assessments, one-time
      evaluations, screening tools, or not commercially available were not used.
      RESULTS: All of the measures included in the review demonstrated adequate content
      and construct validity. Concurrent validity was reported for APIB, NNNS,
      Dubowitz, and GMs. Predictive validity was high for GMs with studies reporting up
      to 100% senstivity for predicting cerebral palsy at the age of 12 to 24 months.
      Interrater reliability was strong for the TIMP (intraclass correlation=0.95), GMs
      (K=0.8), and moderate for the NAPI (r=0.67-0.97). Clinical utility was variable
      for ease of scoring, interpretability, cost, and access. INTERPRETATION: In the
      absence of a criterion standard for neonatal neuromotor assessments, the NNNS and
      APIB have strong psychometric qualities with better utility for research.
      Similarly, the GMs, TIMP, and NAPI have strong psychometric qualities but better
      utility for clinical settings. The GMs has best prediction of future outcome and
      the TIMP has best evaluative validity.

PMID- 22142217
TI  - How to avoid the 'seven deadly sins of surgery'.

PMID- 22142218
TI  - Scedosporium apiospermum catheter-related soft-tissue infection: a case report
      and review of the literature.
AB  - We report a case of catheter-related Scedosporium apiospermum soft-tissue
      infection. This ubiquitous filamentous fungus can cause human infection after
      traumatic subcutaneous implantation of its conidia or their inhalation in near
      drowning cases. It has also been reported as an etiological agent in a growing
      number of hospital-acquired infections.

PMID- 22142219
TI  - Success of posaconazole therapy in a heart transplanted patient with Alternaria
      infectoria cutaneous infection.
AB  - Cutaneous Alternaria spp. infections occur mainly in immunosuppressed patients
      and itraconazole is considered as the drug of choice. We report the case of a 64
      year-old heart transplanted female patient with multiple cutaneous lesions caused
      by Alternaria infectoria. Treatment with posaconazole resulted in complete
      recovery. Due to lower minimal inhibitory concentrations, better distribution and
      less drug interactions than with itraconazole, posaconazole may become the
      antifungal drug to consider in the management of cutaneous infections caused by
      Alternaria spp. in solid organ transplant recipients.

PMID- 22142221
TI  - Molecular mechanisms of the biphasic effects of interferon-gamma on
      osteoclastogenesis.
AB  - Although interferon-gamma (IFN-gamma) potently inhibits osteoclastogenesis, the
      suppressive effect is significantly reduced when osteoclast precursors are pre
      exposed to the receptor activator of NF-kappaB (RANK) ligand (RANKL). However,
      the molecular mechanism underlying the biphasic effects of IFN-gamma on
      osteoclastogenesis remains elusive. Here, we recapitulate the biphasic functions
      of IFN-gamma in osteoclastogenesis in both tissue culture dishes and on bone
      slices. We further demonstrate that IFN-gamma markedly suppresses the RANKL
      induced expression of nuclear factor of activated T-cells c1 (NFATc1) in normal,
      but not RANKL-pretreated bone marrow macrophages (BMMs). Similarly, IFN-gamma
      impairs the activation of the nuclear factor-kappaB (NF-kappaB) and c-Jun N
      terminal kinase (JNK) pathways in normal, but not RANKL-pretreated, BMMs. These
      findings indicate that IFN-gamma inhibits osteoclastogenesis partially by
      suppressing the expression of NFATc1 and the activation of the NF-kappaB and JNK
      pathways. Moreover, IFN-gamma inhibits the RANKL-induced expression of osteoclast
      genes, but RANKL pretreatment reprograms osteoclast genes into a state in which
      they can no longer be suppressed by IFN-gamma, indicating that IFN-gamma inhibits
      osteoclastogenesis by blocking the expression of osteoclast genes. Finally, the
      IVVY(535-538) motif in the cytoplasmic domain of RANK is responsible for
      rendering BMMs refractory to the inhibitory effect of IFN-gamma. Taken together,
      these findings provide important mechanistic insights into the biphasic effects
      of IFN-gamma on osteoclastogenesis.

PMID- 22142220
TI  - Cytokine homologs of human gammaherpesviruses.
AB  - Gammaherpesviruses such as Epstein-Barr virus (EBV, human herpesvirus 4) and
      Kaposi sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) establish
      lifelong infection in the host. To further this lifestyle, they encode homologs
      of cellular cytokines and cytokine receptors with the overarching goal to escape
      from or to blunt host antiviral defenses. EBV encodes mimics of human interleukin
      (hIL)-10 and a G protein-coupled receptor protein with sequence similarity to
      CXCR, whereas KSHV encodes homologs of hIL-6, 3 CC chemokine ligands, and a G
      protein-coupled receptor with sequence similarity to IL8 receptor alpha. This
      review focuses on the EBV IL-10 homolog and the KSHV IL-6 homolog with respect to
      virus biology and pathogenesis of the virus-associated diseases.

PMID- 22142222
TI  - Calyculin A reveals serine/threonine phosphatase protein phosphatase 1 as a
      regulatory nodal point in canonical signal transducer and activator of
      transcription 3 signaling of human microvascular endothelial cells.
AB  - Vascular inflammation is initiated by stimuli acting on endothelial cells. A
      clinical feature of vascular inflammation is increased circulating interleukin 6
      (IL-6) type cytokines such as leukemia inhibitory factor (LIF), but their role in
      vascular inflammation is not fully defined. IL-6 type cytokines activate
      transcription factor signal transducer and activator of transcription 3 (STAT3),
      which has a key role in inflammation and the innate immune response. Canonical
      STAT3 gene induction is due to phosphorylation of (1) Y705, leading to STAT3
      dimerization and DNA binding and (2) S727, enhancing homodimerization and DNA
      binding by recruiting p300/CBP. We asked whether enhancing S727 STAT3
      phosphorylation using the protein phosphatase 1 (PP1) inhibitor, calyculin A,
      would enhance LIF-induced gene expression in human microvascular endothelial
      cells (HMEC-1). Cotreatment with calyculin A and LIF markedly increased STAT3
      S727 phosphorylation, without affecting the increase in the nuclear fraction of
      STAT3 phosphorylated on Y705. PP2A inhibitors, okadaic acid and fostriecin, did
      not enhance STAT3 S727 phosphorylation. Surprisingly, calyculin A eliminated LIF
      induced gene expression: (1) calyculin A reduced binding of nuclear extracts to a
      STAT3 consensus site, thereby reducing the overall level of binding observed with
      LIF; and (2) calyculin A caused p300/CBP phosphorylation, thus resulting in
      reduced acetylation activity and degradation. Together, these findings reveal a
      pivotal role of a protein serine/threonine phosphatases that is likely PP1 in
      HMEC in controlling STAT3 transcriptional activity.

PMID- 22142224
TI  - Ligand exchange on colloidal CdSe nanocrystals using thermally labile tert
      butylthiol for improved photocurrent in nanocrystal films.
AB  - As-prepared CdSe nanocrystals were ligand exchanged using tert-butylthiol, which
      yielded stable CdSe nanocrystal inks in the strong donor solvent tetramethylurea.
      The efficacy of ligand exchange was probed by thermogravimetric analysis (TGA)
      and FT-IR spectroscopy. By studying sequential exchanges of tetradecylphosphonic
      acid and then tert-butylthiol, TGA and energy dispersive X-ray spectroscopic
      evidence clearly demonstrated that the ligand exchange is essentially
      quantitative. The resulting tert-butylthiol-exchanged CdSe nanocrystals undergo
      facile thermal ligand expulsion (<=200  degrees C), which was studied by TGA-mass
      spectrometry. Mild thermal treatment of tert-butylthiol-exchanged CdSe
      nanocrystal films was found to induce loss of quantum confinement (as evidenced
      by UV-vis spectroscopy) and provided for increased electrochemical photocurrent,
      electron mobility, and film stability. Pyridine-exchanged CdSe nanocrystals were
      employed as a control system throughout to demonstrate the beneficial attributes
      of tert-butylthiol exchange; namely, lower organic content, better colloidal
      stability, improved interparticle coupling, and vastly increased electrochemical
      photocurrent response upon illumination.

PMID- 22142223
TI  - Helios transcription factor expression depends on Gsx2 and Dlx1&2 function in
      developing striatal matrix neurons.
AB  - Development of the nervous system is finely regulated by consecutive expression
      of cell-specific transcription factors. Here we show that Helios, a member of the
      Ikaros transcription factor family, is expressed in ectodermal and
      neuroectodermal-derived tissues. During embryonic development, Helios is
      expressed by several brain structures including the lateral ganglionic eminence
      (LGE, the striatal anlage); the cingulated, insular and retrosplenial cortex; the
      hippocampus; and the accessory olfactory bulb. Moreover, Helios is also expressed
      by Purkinje neurons during postnatal cerebellar development. Within the LGE,
      Helios expression follows a dynamic spatio-temporal pattern starting at embryonic
      stages (E14.5), peaking at E18.5, and completely disappearing during postnatal
      development. Helios is expressed by a small population of nestin-positive neural
      progenitor cells located in the subventricular zone as well as by a larger
      population of immature neurons distributed throughout the mantle zone. In the
      later, Helios is preferentially expressed in the matrix compartment, where it
      colocalizes with Bcl11b and Foxp1, well-known markers of striatal projection
      neurons. In addition, we observed that Helios expression is not detected in
      Dlx1/2 and Gsx2 null mutants, while its expression is maintained in Ascl1
      mutants. These findings allow us to introduce a new transcription factor in the
      cascade of events that take part of striatal development postulating the
      existence of at least 4 different neural progenitors in the LGE. An Ascl1
      independent but Gsx2- & Dlx1/2-dependent precursor will express Helios defining a
      new lineage for a subset of matrix striatal neurons.

PMID- 22142225
TI  - Robust heat-inducible gene expression by two endogenous hsp70-derived promoters
      in transgenic Aedes aegypti.
AB  - Aedes aegypti is an important vector of the viruses that cause dengue fever,
      dengue haemorrhagic fever and yellow fever. Reverse genetic approaches to the
      study of gene function in this mosquito have been limited by the lack of a robust
      inducible promoter to allow precise temporal control over a protein-encoding or
      hairpin RNA transgene. Likewise, investigations into the molecular and
      biochemical basis of vector competence would benefit from the ability to activate
      an antipathogen molecule at specific times during infection. We have
      characterized the ability of genomic sequences derived from two Ae. aegypti heat
      shock protein 70 (hsp70) genes to drive heat-inducible expression of a reporter
      in both transient and germline transformation contexts. AaHsp70-luciferase
      transcripts accumulated specifically after heat shock, and displayed a pattern of
      rapid induction and decay similar to endogenous AaHsp70 genes. Luciferase
      expression in transgenic Ae. aegypti increased by ~25-50-fold in whole adults by
      4 h after heat-shock, with significant activity (~20-fold) remaining at 24 h.
      Heat-induced expression was even more dramatic in midgut tissues, with one strain
      showing a ~2500-fold increase in luciferase activity. The AaHsp70 promoters
      described could be valuable for gene function studies as well as for the precise
      timing of the expression of antipathogen molecules.

PMID- 22142226
TI  - Membrane integration of a mitochondrial signal-anchored protein does not require
      additional proteinaceous factors.
AB  - The MOM (mitochondrial outer membrane) contains SA (signal-anchored) proteins
      that bear at their N-terminus a single hydrophobic segment that serves as both a
      mitochondrial targeting signal and an anchor at the membrane. These proteins,
      like the vast majority of mitochondrial proteins, are encoded in the nucleus and
      have to be imported into the organelle. Currently, the mechanisms by which they
      are targeted to and inserted into the OM (outer membrane) are unclear. To shed
      light on these issues, we employed a recombinant version of the SA protein OM45
      and a synthetic peptide corresponding to its signal-anchor segment. Both forms
      are associated with isolated mitochondria independently of cytosolic factors.
      Interaction with mitochondria was diminished when a mutated form of the signal
      anchor was employed. We demonstrate that the signal-anchor peptide acquires an
      alpha-helical structure in a lipid environment and adopted a TM (transmembrane)
      topology within artificial lipid bilayers. Moreover, the peptide's affinity to
      artificial membranes with OM-like lipid composition was much higher than that of
      membranes with ER (endoplasmic reticulum)-like lipid composition. Collectively,
      our results suggest that SA proteins are specifically inserted into the MOM by a
      process that is not dependent on additional proteins, but is rather facilitated
      by the distinct lipid composition of this membrane.

PMID- 22142227
TI  - Infliximab salvage therapy after failure of ciclosporin in corticosteroid
      refractory ulcerative colitis: a multicentre study.
AB  - BACKGROUND: Ciclosporin has proven to be effective in patients with
      corticosteroid-refractory ulcerative colitis (UC). When therapy with this drug
      fails, infliximab can be considered to avoid colectomy. The efficacy and safety
      of this sequential approach remain unknown. AIM: To assess the efficacy and
      safety profile of treatment with infliximab after failure of ciclosporin in
      patients with a corticosteroid-refractory flare of UC. METHODS: Retrospective
      review of medical records of patients with a corticosteroid-refractory flare of
      UC who did not respond to ciclosporin and received salvage therapy with
      infliximab within a month of discontinuing ciclosporin. The severity of the flare
      and response to the treatment were graded using the Lichtiger index. Cumulative
      rates of colectomy were calculated using Kaplan-Meier analysis. Cox regression
      analysis was performed to identify predictors of colectomy. To evaluate the
      safety profile of this treatment strategy, any adverse event occurring after the
      first infusion of infliximab was considered. RESULTS: The study population
      comprised 47 patients with corticosteroid-refractory UC treated with infliximab
      after failure of ciclosporin. The median baseline Lichtiger index was 13. The
      mean time from the last ciclosporin dose to the first infliximab infusion was 6
      days. After the first infliximab infusion, 13% of patients achieved remission,
      and 74% partial response. Of the 35 patients who received the third infliximab
      infusion, 60% achieved remission, and 37% partial response. Fourteen patients
      (30%) underwent colectomy. The rate of adverse events was 23%. One death occurred
      in a 40-year-old man who failed ciclosporin and infliximab and underwent surgery
      10 days after the first infliximab infusion; he died of nosocomial pneumonia.
      CONCLUSIONS: Treatment with infliximab makes it possible to avoid colectomy in
      two-thirds of corticosteroid-refractory UC patients in whom ciclosporin fails.
      However, the rates of adverse events and mortality mean that the decision to
      administer sequential therapy (ciclosporin-infliximab) should be taken on an
      individual basis.

PMID- 22142228
TI  - Lipid profiling by electrospray ionization tandem mass spectrometry and the
      identification of lipid phosphorylation by kinases in potato stolons.
AB  - There is limited information about the involvement of lipids and esterified fatty
      acids in signaling pathways during plant development. The purpose of this study
      was to evaluate the lipid composition and molecular species of potato (Solanum
      tuberosum L., cv. Spunta) stolons and to identify phosphorylated lipids in the
      first two developmental stages of tuber formation. Lipid profiling was determined
      using ESI-MS/MS, a useful method for the determination of the biosynthesis and
      catabolism of lipids based on their fatty acid composition. The most prevalent
      compound identified in this study was phosphatidic acid (PA);
      digalactosyldiacylglycerol (DGDG) was the second most abundant compound. A 34:2
      species was identified in PA, phosphatidylcholine (PC), phosphatidylinositol
      (PI), and phosphatidylethanolamine (PE). The identification of lipid
      phosphorylation by kinases was revealed by the presence of the phosphorylated
      lipids. PA was metabolized to diacylglycerol pyrophosphate (DGPP) by phosphatidic
      acid kinase (PAK). This work establishes a correlation between lipid fatty acid
      composition and lipid metabolism enzymes at the beginning of tuber formation and
      is the first report of PAK activity in the early events of potato tuber
      formation.

PMID- 22142229
TI  - General approach to low-molecular-weight metallogelators via the coordination
      induced gelation of an L-glutamate-based lipid.
AB  - A twin-tailed glutamate-based lipid with a pyridine headgroup was prepared in
      good yield using standard amide coupling and protection/deprotection chemistry.
      The resulting Lewis basic lipid gels a wide array of hydrocarbon solvents at a
      critical gelation concentration (C(g)) of 0.3 wt %. The gelation of more polar
      solvents, such as ethanol, THF, dichloromethane, and chloroform, occurs with a
      C(g) of between 2 and 5 wt %, demonstrating the importance of hydrogen bonding
      interactions in gel formation. The importance of hydrogen bonding in this system
      was also demonstrated by IR observation of the amide bands, which show a
      substantial shift upon gelation. Solutions of this new organogelator with
      concentrations below C(g) rapidly form gels upon the introduction of a wide
      variety of metal salts or complexes, providing a convenient general method for
      the preparation of metallogelators. Spectroscopic evidence suggests that the
      enhanced gelation seen in the metal-containing systems can be explained by a
      cross-linking of gel fibril aggregates similar to those formed by the unmetalated
      gelator.

PMID- 22142230
TI  - Translational and systems medicine.

PMID- 22142232
TI  - Surface urban heat island across 419 global big cities.
AB  - Urban heat island is among the most evident aspects of human impacts on the earth
      system. Here we assess the diurnal and seasonal variation of surface urban heat
      island intensity (SUHII) defined as the surface temperature difference between
      urban area and suburban area measured from the MODIS. Differences in SUHII are
      analyzed across 419 global big cities, and we assess several potential
      biophysical and socio-economic driving factors. Across the big cities, we show
      that the average annual daytime SUHII (1.5 +/- 1.2  degrees C) is higher than the
      annual nighttime SUHII (1.1 +/- 0.5  degrees C) (P < 0.001). But no correlation
      is found between daytime and nighttime SUHII across big cities (P = 0.84),
      suggesting different driving mechanisms between day and night. The distribution
      of nighttime SUHII correlates positively with the difference in albedo and
      nighttime light between urban area and suburban area, while the distribution of
      daytime SUHII correlates negatively across cities with the difference of
      vegetation cover and activity between urban and suburban areas. Our results
      emphasize the key role of vegetation feedbacks in attenuating SUHII of big cities
      during the day, in particular during the growing season, further highlighting
      that increasing urban vegetation cover could be one effective way to mitigate the
      urban heat island effect.

PMID- 22142231
TI  - Endoplasmic reticulum-dependent redox reactions control endoplasmic reticulum
      associated degradation and pathogen entry.
AB  - SIGNIFICANCE: Protein misfolding within the endoplasmic reticulum (ER) is managed
      by an ER quality control system that retro-translocates aberrant proteins into
      the cytosol for proteasomal destruction. This process, known as ER-associated
      degradation, utilizes the action of ER redox enzymes to accommodate the disulfide
      bonded nature of misfolded proteins. Strikingly, various pathogenic viruses and
      toxins co-opt these redox components to reach the cytosol during entry. These
      redox factors thus regulate critical cellular homeostasis and host-pathogen
      interactions. RECENT ADVANCES: Recent studies identify specific members of the
      protein disulfide isomerase (PDI) family, which use their chaperone and catalytic
      activities, in engaging both misfolded ER proteins and pathogens. CRITICAL
      ISSUES: The precise molecular mechanism by which a dedicated PDI family member
      disrupts the disulfide bonds in the misfolded ER proteins and pathogens, as well
      as how they act to unfold these substrates to promote their ER-to-cytosol
      membrane transport, remain poorly characterized. FUTURE DIRECTIONS: How PDI
      family members distinguish folded versus misfolded ER substrates remains
      enigmatic. What physical characteristics surrounding a substrate's disulfide bond
      instruct PDI that it is mispaired or native? For the pathogens, as their
      disulfide bonds normally serve a critical role in providing physical support,
      what conformational changes experienced in the host enable their disulfide bonds
      to be disrupted? A combination of more rigorous biochemical and high-resolution
      structural studies should begin to address these questions.

PMID- 22142233
TI  - Ploidy mosaicism and allele-specific gene expression differences in the
      allopolyploid Squalius alburnoides.
AB  - BACKGROUND: Squalius alburnoides is an Iberian cyprinid fish resulting from an
      interspecific hybridisation between Squalius pyrenaicus females (P genome) and
      males of an unknown Anaecypris hispanica-like species (A genome). S. alburnoides
      is an allopolyploid hybridogenetic complex, which makes it a likely candidate for
      ploidy mosaicism occurrence, and is also an interesting model to address
      questions about gene expression regulation and genomic interactions. Indeed, it
      was previously suggested that in S. alburnoides triploids (PAA composition)
      silencing of one of the three alleles (mainly of the P allele) occurs. However,
      not a whole haplome is inactivated but a more or less random inactivation of
      alleles varying between individuals and even between organs of the same fish was
      seen.In this work we intended to correlate expression differences between
      individuals and/or between organs to the occurrence of mosaicism, evaluating if
      mosaics could explain previous observations and its impact on the assessment of
      gene expression patterns. RESULTS: To achieve our goal, we developed flow
      cytometry and cell sorting protocols for this system generating more homogenous
      cellular and transcriptional samples. With this set-up we detected 10% ploidy
      mosaicism within the S. alburnoides complex, and determined the allelic
      expression profiles of ubiquitously expressed genes (rpl8; gapdh and beta-actin)
      in cells from liver and kidney of mosaic and non-mosaic individuals coming from
      different rivers over a wide geographic range. CONCLUSIONS: Ploidy mosaicism
      occurs sporadically within the S. alburnoides complex, but in a frequency
      significantly higher than reported for other organisms. Moreover, we could
      exclude the influence of this phenomenon on the detection of variable allelic
      expression profiles of ubiquitously expressed genes (rpl8; gapdh and beta-actin)
      in cells from liver and kidney of triploid individuals. Finally, we determined
      that the expression patterns previously detected only in a narrow geographic
      range is not a local restricted phenomenon but is pervasive in rivers where S.
      pyrenaicus is sympatric with S. alburnoides.We discuss mechanisms that could lead
      to the formation of mosaic S. alburnoides and hypothesise about a relaxation of
      the mechanisms that impose a tight control over mitosis and ploidy control in
      mixoploids.

PMID- 22142234
TI  - Variation in grain arsenic assessed in a diverse panel of rice (Oryza sativa)
      grown in multiple sites.
AB  - * Inorganic arsenic (As(i) ) in rice (Oryza sativa) grains is a possible threat
      to human health, with risk being strongly linked to total dietary rice
      consumption and consumed rice As(i) content. This study aimed to identify the
      range and stability of genetic variation in grain arsenic (As) in rice. * Six
      field trials were conducted (one each in Bangladesh and China, two in Arkansas,
      USA over 2 yr, and two in Texas, USA comparing flooded and nonflood treatments)
      on a large number of common rice cultivars (c. 300) representing genetic
      diversity among international rice cultivars. * Within each field there was a 3
      34 fold range in grain As concentration which varied between rice subpopulations.
      Importantly, As(i) correlated strongly with total As among a subset of 40
      cultivars harvested in Bangladesh and China. * Genetic variation at all field
      sites was a large determining factor for grain As concentration, indicating that
      cultivars low in grain As could be developed through breeding. The temperate
      japonicas exhibited lower grain As compared with other subpopulations. Effects
      for year, location and flooding management were also statistically significant,
      suggesting that breeding strategies must take into account environmental factors.

PMID- 22142235
TI  - Thermal hysteresis in the backbone and side-chain dynamics of the elastin mimetic
      peptide [VPGVG]3 revealed by 2H NMR.
AB  - We report on experimental measurements of the backbone and side-chain dynamics of
      the elastin mimetic peptide [VPGVG](3) by (2)H NMR echo spectroscopy and 2D T(1)
      T(2) correlation relaxometry. The T(1) and T(2) relaxation times of the Gly alpha
      deuterons and Val alpha-, beta-, and gamma-deuterons of a hydrated sample reveal
      a thermal hysteresis when the temperature is raised from -10 to 45  degrees C and
      then subsequently cooled back to -10  degrees C. In addition, near 30  degrees C
      we observe a reduction in the slope of the T(1)(T) and T(2)(T) heating curves,
      indicating a structural change that appears to be correlated well to the known
      inverse temperature transition of this peptide. The thermal dependence of the
      correlation times of the Gly alpha-deuterons are well fit by an Arrhenius Law,
      from which we measured E(act) = (20.0 +/- 3.1) kJ/mol when the sample is heated
      and E(act) = (10.9 +/- 2.8) kJ/mol when cooled. Molecular dynamics simulations
      support the notion that the measured activation energy is determined largely by
      the extent of localized water, which is observed to decrease with increasing
      temperature from approximately 25 to 42  degrees C.

PMID- 22142237
TI  - Willingness-to-pay for benefits associated with basal insulin treatment of type 2
      diabetes.
AB  - Data from a 20-week trial comparing insulin detemir and neutral protamine
      Hagedorn (NPH) insulin in insulin-naive people with type 2 diabetes were analyzed
      using willingness-to-pay (WTP) data, a proxy for patient preference. The
      advantages of insulin detemir relative to NPH insulin with respect to a lower
      hypoglycemia rate and less weight gain were associated with a value of ?27.87 per
      month.

PMID- 22142236
TI  - Discovery and characterization of novel microRNAs during endothelial
      differentiation of human embryonic stem cells.
AB  - MicroRNAs (miRNAs) are small RNAs that participate in the regulation of genes
      associated with the differentiation and proliferation. In this study, 5 novel
      miRNAs were identified from human mesenchymal stem cells and characterized using
      various analyses. To investigate the potential functions associated with the
      regulation of cell differentiation, the differences in miRNA expression were
      examined in undifferentiated and differentiated human embryonic stem (ES) cells
      using reverse transcription (RT)-PCR analysis. Specifically, 3 miRNAs exhibited
      decreased expression levels in human umbilical vein endothelial cells (HUVECs)
      and endothelial cells derived from human ES cells. Putative target genes related
      to differentiation or maturation of endothelial cells were predicted by seed
      sequences of 2 novel miRNAs and analyzed for their expression via miRNA-mediated
      regulation using a luciferase assay. In HUVECs, CDH5 gene expression was directly
      repressed by hsa-miR-6086. Similarly, hsa-miR-6087 significantly downregulated
      endoglin expression. Therefore, the roles of these 2 miRNAs may be to directly
      suppress their target genes, popularly known as endothelial cell markers. Taken
      together, our results demonstrate that several novel miRNAs perform critical
      roles in human endothelial cell development.

PMID- 22142238
TI  - Lactococcus lactis HemW (HemN) is a haem-binding protein with a putative role in
      haem trafficking.
AB  - Lactococcus lactis cannot synthesize haem, but when supplied with haem, expresses
      a cytochrome bd oxidase. Apart from the cydAB structural genes for this oxidase,
      L. lactis features two additional genes, hemH and hemW (hemN), with conjectured
      functions in haem metabolism. While it appears clear that hemH encodes a
      ferrochelatase, no function is known for hemW. HemW-like proteins occur in
      bacteria, plants and animals, and are usually annotated as CPDHs
      (coproporphyrinogen III dehydrogenases). However, such a function has never been
      demonstrated for a HemW-like protein. We here studied HemW of L. lactis and
      showed that it is devoid of CPDH activity in vivo and in vitro. Recombinantly
      produced, purified HemW contained an Fe-S (iron-sulfur) cluster and was dimeric;
      upon loss of the iron, the protein became monomeric. Both forms of the protein
      covalently bound haem b in vitro, with a stoichiometry of one haem per monomer
      and a KD of 8 MUM. In vivo, HemW occurred as a haem-free cytosolic form, as well
      as a haem-containing membrane-associated form. Addition of L. lactis membranes to
      haem-containing HemW triggered the release of haem from HemW in vitro. On the
      basis of these findings, we propose a role of HemW in haem trafficking. HemW-like
      proteins form a distinct phylogenetic clade that has not previously been
      recognized.

PMID- 22142239
TI  - A co-ordinated interaction between CTCF and ER in breast cancer cells.
AB  - BACKGROUND: CCCTC-binding factor (CTCF) is a conserved zinc finger transcription
      factor that is involved in both intra- and interchromasomal looping. Recent
      research has shown a role for CTCF in estrogen receptor (ER) biology, at some
      individual loci, but a multi-context global analysis of CTCF binding and
      transcription activity is lacking. RESULTS: We now map CTCF binding genome wide
      in breast cancer cells and find that CTCF binding is unchanged in response to
      estrogen or tamoxifen treatment. We find a small but reproducible set of CTCF
      binding events that overlap with both the nuclear receptor, estrogen receptor,
      and the forkhead protein FOXA1. These overlapping binding events are likely
      functional as they are biased towards estrogen-regulated genes, compared to
      regions lacking either CTCF or ER binding. In addition we identify cell-line
      specific CTCF binding events. These binding events are more likely to be
      associated with cell-line specific ER binding events and are also more likely to
      be adjacent to genes that are expressed in that particular cell line. CONCLUSION:
      The evolving role for CTCF in ER biology is complex, but is likely to be
      multifunctional and possibly influenced by the specific genomic locus. Our data
      suggest a positive, pro-transcriptional role for CTCF in ER-mediated gene
      expression in breast cancer cells. CTCF not only provides boundaries for
      accessible and 'protected' transcriptional blocks, but may also influence the
      actual binding of ER to the chromatin, thereby modulating the estrogen-mediated
      gene expression changes observed in breast cancer cells.

PMID- 22142240
TI  - Spontaneous periodic hypothermia and hyperhidrosis: its relation with spontaneous
      endogenous hypermelatoninemia.

PMID- 22142241
TI  - Slow magnetic relaxation at zero field in the tetrahedral complex [Co(SPh)4]2-.
AB  - The Ph(4)P(+) salt of the tetrahedral complex [Co(SPh)(4)](2-), possessing an S =
      (3)/(2) ground state with an axial zero-field splitting of D = -70 cm(-1),
      displays single-molecule magnet behavior in the absence of an applied magnetic
      field. At very low temperatures, ac magnetic susceptibility data show the
      magnetic relaxation time, tau, to be temperature-independent, while above 2.5 K
      thermally activated Arrhenius behavior is apparent with U(eff) = 21(1) cm(-1) and
      tau(0) = 1.0(3) * 10(-7) s. Under an applied field of 1 kOe, tau more closely
      approximates Arrhenius behavior over the entire temperature range. Upon dilution
      of the complex within a matrix of the isomorphous compound
      (Ph(4)P)(2)[Zn(SPh)(4)], ac susceptibility data reveal the molecular nature of
      the slow magnetic relaxation and indicate that the quantum tunneling pathway
      observed at low temperatures is likely mediated by intermolecular dipolar
      interactions.

PMID- 22142242
TI  - Erv2 and quiescin sulfhydryl oxidases: Erv-domain enzymes associated with the
      secretory pathway.
AB  - SIGNIFICANCE: Members of the Erv/ALR/QSOX protein family contain an Erv sequence
      module and catalyze protein disulfide bond formation. Erv enzymes impact protein
      function within and outside cells that affects both normal and malignant cell
      growth. This protein family is named for its founding members: Erv1 (essential
      for respiratory and vegetative growth 1) and ALR (augmenter of liver
      regeneration), homologous mitochondrial proteins from yeast and mammals,
      respectively, and QSOX (quiescin sulfhydryl oxidase), an oxidase secreted from
      quiescent cells. This review will focus on a subset of Erv proteins that are
      localized within the secretory pathway: Erv2-like proteins, proteins present in
      the endoplasmic reticulum of fungi, and QSOX proteins, proteins localized within
      the secretory pathway and extracellular space and present in most eukaryotes, but
      not fungi. RECENT ADVANCES: A wealth of structural and biochemical data has been
      obtained for Erv2 and QSOX proteins. These data have identified a generally
      conserved catalytic mechanism and structure for the Erv2 and QSOX proteins with
      unique features for each enzyme. CRITICAL ISSUES: Many fundamental questions
      remain about the activity for these proteins in living cells including the
      partners, pathways, and locations utilized by these enzymes in vivo. FUTURE
      DIRECTIONS: A more comprehensive understanding of the cellular roles for Erv2 and
      QSOX enzymes will require identification of their partners and substrates. Also,
      determining when Erv2 and QSOX function during growth and development, and how
      changes in levels of active Erv2 and QSOX impact cell function, is necessary to
      facilitate a better understanding of these intriguing enzymes.

PMID- 22142243
TI  - Volatile organic compounds and metal leaching from composite products made from
      fiberglass-resin portion of printed circuit board waste.
AB  - This study focused on the volatile organic compounds (VOCs) and metal leaching
      from three kinds of composite products made from fiberglass-resin portion (FRP)
      of crushed printed circuit board (PCB) waste, including phenolic molding compound
      (PMC), wood plastic composite (WPC), and nonmetallic plate (NMP). Released VOCs
      from the composite products were quantified by air sampling on adsorbent followed
      by thermal desorption and GC-MS analysis. The results showed that VOCs emitted
      from composite products originated from the added organic components during
      manufacturing process. Phenol in PMC panels came primarily from phenolic resin,
      and the airborne concentration of phenol emitted from PMC product was 59.4 +/-
      6.1 MUg/m(3), which was lower than odor threshold of 100% response for phenol
      (180 MUg/m(3)). VOCs from WPC product mainly originated from wood flour, e.g.,
      benzaldehyde, octanal, and d-limonene were emitted in relatively low
      concentrations. For VOCs emitted from NMP product, the airborne concentration of
      styrene was the highest (633 +/- 67 MUg/m(3)). Leaching characteristics of metal
      ions from composite products were tested using acetic acid buffer solution and
      sulphuric acid and nitric acid solution. Then the metal concentrations in the
      leachates were tested by ICP-AES. The results showed that only the concentration
      of Cu (average = 893 mg/L; limit = 100 mg/L) in the leachate solution of the FRP
      using acetic acid buffer solution exceeded the standard limit. However,
      concentrations of other metal ions (Pb, Cd, Cr, Ba, and Ni) were within the
      standard limit. All the results indicated that the FRP in composite products was
      not a major concern in terms of environmental assessment based upon VOCs tests
      and leaching characteristics.

PMID- 22142244
TI  - A vision for a biomedical cloud.
AB  - We present a vision for a Biomedical Cloud that draws on progress in the fields
      of Genomics, Systems Biology and biomedical data mining. The successful fusion of
      these areas will combine the use of biomarkers, genetic variants, and
      environmental variables to build predictive models that will drastically increase
      the specificity and timeliness of diagnosis for a wide range of common diseases,
      whilst delivering accurate predictions about the efficacy of treatment options.
      However, the amount of data being generated by each of these fields is
      staggering, as is the task of managing and analysing it. Adequate computing
      infrastructure needs to be developed to assemble, manage and mine the enormous
      and rapidly growing corpus of 'omics' data along with clinical information. We
      have now arrived at an intersection point between genome technology, cloud
      computing and biological data mining. This intersection point provides a launch
      pad for developing a globally applicable cloud computing platform capable of
      supporting a new paradigm of data intensive, cloud-enabled predictive medicine.

PMID- 22142245
TI  - Hydrogen-deuterium exchange mass spectrometry reveals the interaction of Fenna
      Matthews-Olson protein and chlorosome CsmA protein.
AB  - In green-sulfur bacterial photosynthesis, excitation energy absorbed by a
      peripheral antenna structure known as the chlorosome is sequentially transferred
      through a baseplate protein to the Fenna-Matthews-Olson (FMO) antenna protein and
      into the reaction center, which is embedded in the cytoplasmic membrane. The
      molecular details of the optimized photosystem architecture required for
      efficient energy transfer are only partially understood. We address here the
      question of how the baseplate interacts with the FMO protein by applying
      hydrogen/deuterium exchange coupled with enzymatic digestion and mass
      spectrometry analysis to reveal the binding interface of the FMO antenna protein
      and the CsmA baseplate protein. Several regions on the FMO protein, represented
      by peptides consisting of 123-129, 140-149, 150-162, 191-208, and 224-232, show
      significant decreases of deuterium uptake after CsmA binding. The results
      indicate that the CsmA protein interacts with the Bchl a #1 side of the FMO
      protein. A global picture including peptide-level details for the architecture of
      the photosystem from green-sulfur bacteria can now be drawn.

PMID- 22142246
TI  - Activity of meadowfoam (Limnanthes alba) seed meal glucolimnanthin degradation
      products against soilborne pathogens.
AB  - Meadowfoam (Limnanthes alba L.) is a herbaceous winter-spring annual grown as a
      commercial oilseed crop. The meal remaining after oil extraction from the seed
      contains up to 4% of the glucosinolate glucolimnanthin. Degradation of
      glucolimnanthin yields toxic breakdown products, and therefore the meal may have
      potential in the management of soilborne pathogens. To maximize the pest
      suppressive potential of meadowfoam seed meal, it would be beneficial to know the
      toxicity of individual glucolimnanthin degradation products against specific
      soilborne pathogens. Meloidogyne hapla second-stage juveniles (J2) and Pythium
      irregulare and Verticillium dahliae mycelial cultures were exposed to
      glucolimnanthin as well as its degradation products. Glucolimnanthin and its
      degradation product, 2-(3-methoxyphenyl)acetamide, were not toxic to any of the
      soilborne pathogens at concentrations up to 1.0 mg/mL. Two other degradation
      products, 2-(3-methoxymethyl)ethanethioamide and 3-methoxyphenylacetonitrile,
      were toxic to M. hapla and P. irregulare but not V. dahliae. The predominant
      enzyme degradation product, 3-methoxybenzyl isothiocyanate, was the most toxic
      compound against all of the soilborne pathogens, with M. hapla being the most
      sensitive with EC(50) values (0.0025 +/- 0.0001 to 0.0027 +/- 0.0001 mg/mL) 20-40
      times lower than estimated EC(50) mortality values generated for P. irregulare
      and V. dahliae (0.05 and 0.1 mg/mL, respectively). The potential exists to
      manipulate meadowfoam seed meal to promote the production of specific degradation
      products. The conversion of glucolimnanthin into its corresponding isothiocyanate
      should optimize the biopesticidal properties of meadowfoam seed meal against M.
      hapla, P. irregulare, and V. dahliae.

PMID- 22142248
TI  - All professionals are equal but some professionals are more equal than others?
      Dominance, status and efficiency in Swedish interprofessional teams.
AB  - This study explored status differences in interprofessional teams and their link
      with efficiency. In total, 62 teams (423 individuals) from occupational health
      care, psychiatry, rehabilitation and school health-care responded to a
      questionnaire. Fifty-four of those teams (360 individuals) also participated in
      an observation session simulating problem-solving team meetings. Data were
      reduced to a number of indexes: self-assessed/perceived equality, functional
      influence and efficiency; and observed verbal dominance/activity and problem
      solving capacity. Perceived status differences within the teams appeared
      moderate, irrespective of professional belonging. With respect to verbal
      dominance during meetings, however, the findings revealed a hierarchy with
      psychologists, physicians and social workers at the top together with special
      education teachers. No relationship was found between self-assessed efficiency
      and actual problem-solving nor between observed verbal activity and problem
      solving. The findings suggest that different problems may demand different
      prerequisites to be solved effectively: successful solving of simple convergent
      problems correlated negatively with equality, whereas functional influence was a
      predictor of success with respect to divergent, complex problem-solving. The
      findings raise questions about leadership and procedures during team meetings.

PMID- 22142249
TI  - Computational fluid dynamics models of conifer bordered pits show how pit
      structure affects flow.
AB  - * The flow of xylem sap through conifer bordered pits, particularly through the
      pores in the pit membrane, is not well understood, but is critical for an
      understanding of water transport through trees. * Models solving the Navier
      Stokes equation governing fluid flow were based on the geometry of bordered pits
      in black spruce (Picea mariana) and scanning electron microscopy images showing
      details of the pores in the margo of the pit membrane. * Solutions showed that
      the pit canals contributed a relatively small fraction of resistance to flow,
      whereas the torus and margo pores formed a large fraction, which depended on the
      structure of the individual pit. The flow through individual pores in the margo
      was strongly dependent on pore area, but also on the radial location of the pore
      with respect to the edge of the torus. * Model results suggest that only a few
      per cent of the pores in the margo account for nearly half of the flow and these
      pores tend to be located in the inner region of the margo where their
      contribution will be maximized. A high density of strands in outer portions of
      the margo (hence narrower pores) may be more significant for mechanical support
      of the torus.

PMID- 22142250
TI  - Robot-assisted laparoscopic retroperitoneal lymph node dissection in an
      adolescent population.
AB  - Abstract   Laparoscopic retroperitoneal lymph node dissection (RPLND) has been
      shown to be safe and effective in appropriately selected pediatric and adolescent
      patients with paratesticular rhabdomyosarcoma (RMS) and testicular germ-cell
      tumors (T-GCT). While the use of robot-assisted laparoscopy has expanded rapidly
      in many areas, there are very limited reports of its use with RPLND. We present
      two cases of adolescents who were treated using robot-assisted laparoscopic RPLND
      (R-RPLND)-one with paratesticular RMS (PT-RMS) and one with testicular GCT (T
      GCT)-with good outcomes and low morbidity.

PMID- 22142251
TI  - Controlling the structure and size of Au nanocrystals by annealing and ion
      sputtering.
AB  - In situ thermal annealing was used for the first time to observe directly that Au
      nanoparticles, which were originally fully embedded in the near-surface region of
      TiO(2), can be tailored into hemispheres exposed at the surface at elevated
      temperature. Precise control of the size of the Au hemispheres was achieved by
      subsequent low-energy ion sputtering. This method can be used to control the
      structure and size of a wide variety of nanoparticles in a matrix where surface
      structure and particle size are required to obtain specific material properties.

PMID- 22142252
TI  - Peculiarity of aqueous solutions of 2,2,2-trifluoroethanol.
AB  - Aqueous solutions of 2,2,2-trifluoroethanol appear to show a structural
      transition at alcohol mole fraction equal to x(TFE) = 0.05, which can be
      concluded from a discontinuity of the speed of sound. At the same concentration,
      a discontinuity was observed in the parameters of the long-living component of
      the positron annihilation spectrum. Moreover, the partial molar volumes of
      components show transition-like behavior in the range of low solute contents,
      which is significantly different from nonsubstituted ethanol. The peculiarities
      of the low concentration system correlate with minor infrared spectra changes
      assigned to a mode composed of the CH(2) bending and CF(3) stretching internal
      vibrations being sensitive to polarity of the hydration shell surrounding the
      solute. The majority of the spectral changes arise from a gradual shift of the
      equilibrium between trans <-> gauche isomers when the composition of the solution
      is changing. A possible explanation for the peculiar behavior of the system is a
      thermodynamic equilibrium between hydrated monomers and dimers at that respective
      mole number.

PMID- 22142253
TI  - Maternal parenting as a mediator of the relationship between intimate partner
      violence and effortful control.
AB  - The current study examined the relationship between intimate partner violence
      (IPV), maternal parenting behaviors, and child effortful control in a diverse
      sample of 705 families living in predominantly low-income, rural communities.
      Using structural equation modeling, the authors simultaneously tested whether
      observed sensitive parenting and/or harsh-intrusive parenting over the toddler
      years mediated the relationship between early IPV and later effortful control.
      Results suggest that parenting behaviors fully mediate this relationship.
      Although higher levels of IPV were associated with both higher levels of harsh
      intrusive parenting and lower levels of sensitive supportive parenting, only
      sensitive supportive parenting was associated with later effortful control when
      both parenting indices were considered in the same model.

PMID- 22142254
TI  - A hybrid BAC physical map of potato: a framework for sequencing a heterozygous
      genome.
AB  - BACKGROUND: Potato is the world's third most important food crop, yet cultivar
      improvement and genomic research in general remain difficult because of the
      heterozygous and tetraploid nature of its genome. The development of physical map
      resources that can facilitate genomic analyses in potato has so far been very
      limited. Here we present the methods of construction and the general statistics
      of the first two genome-wide BAC physical maps of potato, which were made from
      the heterozygous diploid clone RH89-039-16 (RH). RESULTS: First, a gel
      electrophoresis-based physical map was made by AFLP fingerprinting of 64478 BAC
      clones, which were aligned into 4150 contigs with an estimated total length of
      1361 Mb. Screening of BAC pools, followed by the KeyMaps in silico anchoring
      procedure, identified 1725 AFLP markers in the physical map, and 1252 BAC contigs
      were anchored the ultradense potato genetic map. A second, sequence-tag-based
      physical map was constructed from 65919 whole genome profiling (WGP) BAC
      fingerprints and these were aligned into 3601 BAC contigs spanning 1396 Mb. The
      39733 BAC clones that overlap between both physical maps provided anchors to 1127
      contigs in the WGP physical map, and reduced the number of contigs to around 2800
      in each map separately. Both physical maps were 1.64 times longer than the 850 Mb
      potato genome. Genome heterozygosity and incomplete merging of BAC contigs are
      two factors that can explain this map inflation. The contig information of both
      physical maps was united in a single table that describes hybrid potato physical
      map. CONCLUSIONS: The AFLP physical map has already been used by the Potato
      Genome Sequencing Consortium for sequencing 10% of the heterozygous genome of
      clone RH on a BAC-by-BAC basis. By layering a new WGP physical map on top of the
      AFLP physical map, a genetically anchored genome-wide framework of 322434
      sequence tags has been created. This reference framework can be used for
      anchoring and ordering of genomic sequences of clone RH (and other potato
      genotypes), and opens the possibility to finish sequencing of the RH genome in a
      more efficient way via high throughput next generation approaches.

PMID- 22142255
TI  - Cerebral palsy, brain lesions, and thrombophilic genetic factors.

PMID- 22142256
TI  - Structural rules for the chiral supramolecular organization of OPE-based
      discotics: induction of helicity and amplification of chirality.
AB  - A systematic study on the structural rules that regulate the chiral
      supramolecular organization of oligo(phenylene ethynylene) (OPE)-based discotics
      is presented. This study is based on the chirooptical properties of two different
      series of triangular shape OPEs. The first of them is composed by OPE-based
      trisamides with a variable number of chiral side chains (compounds 1) that self
      assemble following a cooperative mechanism. The CD experiments carried out with
      these desymmetrized trisamides demonstrate that only one stereogenic center is
      sufficient to achieve a helical organization with a preferred handedness.
      However, the ability to amplify the chirality decreases upon decreasing the
      number of stereocenters at the peripheral side chains. The second series is
      constituted by triangular shape OPEs with a variable number of ether and amide
      functional groups and constant absolute configuration of the stereogenic centers
      at all of the peripheral chains (compounds 2). These compounds do not self
      assemble into helical aggregates as demonstrated by the corresponding CD studies.
      The amplification of chirality observed in the mixtures of some of the components
      of both series has been investigated. The combination of chiral trisamide 1d with
      chiral but nonhelical 2b or 2c does not produce an amplification of chirality
      most probably due to the mismatch between the stereogenic centers of both
      components. However, the combination of achiral trisamide 1a with chiral but
      nonhelical bisamide 2c generates, in a cooperative manner, helical structures
      with a preferred handedness in a process involving the transfer of helicity from
      1a to 2c and the transfer of chirality from 2c to 1a. The structural features of
      the OPE discotics also exert a strong influence on the columnar aggregates. Thus,
      while achiral 1a bundles into thick filaments to form an organogel, the gelation
      ability of these triangular OPEs decreases upon increasing the number of
      stereogenic centers, being totally canceled for compounds 2 in which the amide
      functionalities are replaced by ether linkages. Finally, we have also registered
      AFM images of the helical aggregates obtained from the mixture of 1a+2c, which
      implies an efficient transfer of the chiral objects from solution to surfaces.
      The study presented herein increases the understanding of the structural rules
      that regulate the chiral supramolecular organization of discrete molecules in
      general and, more specifically, those based on pi-conjugated oligomers.

PMID- 22142258
TI  - The protein disulfide isomerase family: key players in health and disease.
AB  - SIGNIFICANCE: Protein disulfide isomerase (PDI) and its homologs have essential
      roles in the oxidative folding and chaperone-mediated quality control of proteins
      in the secretory pathway. In this review, the importance of PDI in health and
      disease will be examined, using examples from the fields of lipid homeostasis,
      hemostasis, infectious disease, cancer, neurodegeneration, and infertility.
      RECENT ADVANCES: Recent structural studies, coupled with cell biological,
      biochemical, and clinical approaches, have demonstrated that PDI family proteins
      are involved in a wide range of physiological and disease processes. CRITICAL
      ISSUES: Critical issues in the field include understanding how and why a PDI
      family member is involved in a given disease, and defining the physiological
      client specificity of the various PDI proteins when they are expressed in
      different tissues. FUTURE DIRECTIONS: Future directions are likely to include the
      development of new and more specific reagents to study and manipulate PDI family
      function. The development of conditional mouse models in concert with clinical
      data will help us to understand the in vivo function of the different PDIs at the
      organism level. Taken together with advances in structural biology and
      biochemical studies, this should help us to further understand and modify PDIs'
      functional interactions.

PMID- 22142257
TI  - Effects of acutely inhibiting PI3K isoforms and mTOR on regulation of glucose
      metabolism in vivo.
AB  - In in vitro studies class-I PI3Ks (phosphoinositide 3-kinases), class-II PI3Ks
      and mTOR (mammalian target of rapamycin) have all been described as having roles
      in the regulation of glucose metabolism. The relative role each plays in the
      normal signalling processes regulating glucose metabolism in vivo is less clear.
      Knockout and knockin mouse models have provided some evidence that the class-I
      PI3K isoforms p110alpha, p110beta, and to a lesser extent p110gamma, are
      necessary for processes regulating glucose metabolism and appetite. However, in
      these models the PI3K activity is chronically reduced. Therefore we analysed the
      effects of acutely inhibiting PI3K isoforms alone, or PI3K and mTOR, on glucose
      metabolism and food intake. In the present study impairments in glucose
      tolerance, insulin tolerance and increased hepatic glucose output were observed
      in mice treated with the pan-PI3K/mTOR inhibitors PI-103 and NVP-BEZ235. The
      finding that ZSTK474 has similar effects indicates that these effects are due to
      inhibition of PI3K rather than mTOR. The p110alpha-selective inhibitors PIK75 and
      A66 also induced these phenotypes, but inhibitors of p110beta, p110delta or
      p110gamma induced only minor effects. These drugs caused no significant effects
      on BMR (basal metabolic rate), O2 consumption or water intake, but BEZ235, PI-103
      and PIK75 did cause a small reduction in food consumption. Surprisingly, pan-PI3K
      inhibitors or p110alpha inhibitors caused reductions in animal movement, although
      the cause of this is not clear. Taken together these studies provide
      pharmacological evidence to support a pre-eminent role for the p110alpha isoform
      of PI3K in pathways acutely regulating glucose metabolism.

PMID- 22142259
TI  - Co-detoxification of transformer oil-contained PCBs and heavy metals in medical
      waste incinerator fly ash under sub- and supercritical water.
AB  - The simultaneous detoxification processes of transformer oil-contained PCBs and
      heavy metals in medical waste incinerator (MWI) fly ash were developed under sub-
      and supercritical water. The addition of MWI fly ash to transformer oil-contained
      PCBs was found to increase the destruction efficiency of PCBs, at the same time,
      it facilitated reducing the leaching concentration of toxic metals from residues
      (obtained after reaction) for harmless disposal. In this study, we elucidated
      primarily the catalysis possibility of heavy metals in raw MWI fly ash for PCBs
      degradation by adopting the sequential extraction procedure. For both MWI fly
      ashes, more than 90% destruction efficiency of PCBs was achieved at >=375 
      degrees C for 30 min, and trichlorobenzene (TCB) existing in the transformer oil
      was also completely decomposed. The correlation of catalytic performance to PCBs
      degradation was discussed based on structural characteristics and dechlorinated
      products. Likewise, such process rendered residues innocuous through
      supercritical water treatment for reuse or disposal in landfill.

PMID- 22142260
TI  - Application of a molecularly imprinted polymer for the extraction of kukoamine a
      from potato peels.
AB  - A molecularly imprinted polymer (MIP) for the purification of N(1),N(12)
      bis(dihydrocaffeoyl)spermine (kukoamine A) was computationally designed and
      tested. The properties of the polymer were characterized. The protocol of the
      solid phase extraction (SPE) of kukoamine A from potato peels was optimized. A
      HPLC-MS method for the quantification of kukoamine A was developed and used for
      all optimization studies. The capacity of the MIP in relation to kukoamine A from
      the potato peels extract was estimated at 54 mg/g of the polymer. The kukoamine A
      purified from potato extract using MIP was exceptionally pure (~ 90%). Although
      the corresponding blank polymer was less selective than the MIP for the
      extraction of kukoamine A from the potato extract, it was shown that the blank
      polymer could be effectively used for the purification of the crude synthetic
      kukoamine (polymer capacity = 80 mg of kukoamine A/g of the adsorbent, kukoamine
      A purity ~ 86%). Therefore, selective adsorbents could be computationally
      designed for other plant products, allowing their purification in quantities that
      would be sufficient for more detailed studies and potential practical
      applications.

PMID- 22142261
TI  - An updated analysis of hepatitis C virus genotypes and subtypes based on the
      complete coding region.
AB  - BACKGROUND: The hepatitis C virus (HCV) genomic database is expanding rapidly.
      AIMS: There is a need to provide an updated phylogenetic tree analysis based on
      the complete coding region of HCV. METHODS: All available HCV complete genome
      sequences in the HCV databases available through October 2010 were analyzed.
      RESULTS: The assignment of all known complete sequences up-to-date confirmed the
      previous six major genotypes and one new sequence, which have been provisionally
      assigned as subtype 7a. New recombinant forms of HCV, although uncommon, have
      been detected and were found to have different crossover points. CONCLUSION: This
      updated analysis based on the complete region of HCV confirmed the validity of
      the previously assigned genotypes/subtypes and provided an up-to-date reference
      for future basic research and clinical studies.

PMID- 22142262
TI  - Ultrafast ligand dynamics in the heme-based GAF sensor domains of the histidine
      kinases DosS and DosT from Mycobacterium tuberculosis.
AB  - The transcriptional regulator DosR from M. tuberculosis plays a crucial role in
      the virulence to dormancy transition of the pathogen. DosR can be activated by
      DosT and DosS, two histidine kinases with heme-containing sensor GAF domains,
      capable of diatomic ligand binding. To investigate the initial processes
      occurring upon ligand dissociation, we performed ultrafast time-resolved
      absorption spectroscopy of the isolated sensor domains ligated with O(2), NO, and
      CO. The results reveal a relatively closed heme pocket for both proteins. For
      DosT the yield of O(2) escape from the heme pocket on the picoseconds time scale
      upon photodissociation was found to be very low (1.5%), similar to other heme
      based oxygen sensor proteins, implying that this sensor acts as an effective O(2)
      trap. Remarkably, this yield is an order of magnitude higher in DosS (18%). For
      CO, by contrast, the fraction of CO rebinding within the heme pocket is higher in
      DosS. Experiments with mutant DosT sensor domains and molecular dynamics
      simulations indicate an important role in ligand discrimination of the distal
      tyrosine, present in both proteins, which forms a hydrogen bond with heme-bound
      O(2). We conclude that despite their similarity, DosT and DosS display ligand
      specific different primary dynamics during the initial phases of intraprotein
      signaling. The distal tyrosine, present in both proteins, plays an important role
      in these processes.

PMID- 22142263
TI  - Predictive mathematical models of cancer signalling pathways.
AB  - Complex intracellular signalling networks integrate extracellular signals and
      convert them into cellular responses. In cancer cells, the tightly regulated and
      fine-tuned dynamics of information processing in signalling networks is altered,
      leading to uncontrolled cell proliferation, survival and migration. Systems
      biology combines mathematical modelling with comprehensive, quantitative, time
      resolved data and is most advanced in addressing dynamic properties of
      intracellular signalling networks. Here, we introduce different modelling
      approaches and their application to medical systems biology, focusing on the
      identifiability of parameters in ordinary differential equation models and their
      importance in network modelling to predict cellular decisions. Two related
      examples are given, which include processing of ligand-encoded information and
      dual feedback regulation in erythropoietin (Epo) receptor signalling. Finally, we
      review the current understanding of how systems biology could foster the
      development of new treatment strategies in the context of lung cancer and
      anaemia.

PMID- 22142264
TI  - Health care costs associated with traumatic brain injury and psychiatric illness
      in adults.
AB  - A cohort design was used to determine the contribution of traumatic brain injury
      (TBI) and psychiatric illness to health care costs for adolescents and adults in
      the 3 years following mild or moderate-to-severe TBI compared to a matched cohort
      without TBI, controlling for confounders. In all, 3756 subjects 15 years or older
      from a large health maintenance organization database were examined. We
      identified subjects who sustained a TBI in 1993 (n=939) and selected three
      control subjects per TBI-exposed subject (n=2817), matched for age, sex, and
      enrollment at the time of injury. Unadjusted mean costs in 2009-adjusted dollars
      were compared using Kruskal-Wallis tests and Mann-Whitney U tests, and adjusted
      mean costs were compared using gamma regression analyses. Average costs were 76%
      higher in the 3 years after injury for the mild TBI group, and 5.75 times greater
      for the moderate-to-severe TBI group compared to controls. The presence of
      psychiatric illness was associated with more than doubling of total costs for
      both inpatient and outpatient non-mental health care. Gamma regression analyses
      confirmed significantly higher costs in patients with TBI or psychiatric illness.
      A significant interaction between moderate-to-severe TBI and psychiatric illness
      indicated a 3.39 times greater cost among patients with both exposures compared
      with those exposed to moderate-to-severe TBI without psychiatric illness. TBI and
      psychiatric illness were each associated with significant increases in health
      care costs; those with the combination of moderate-to-severe TBI and psychiatric
      illness had much higher costs than any other group.

PMID- 22142266
TI  - Thyroid status two decades after salt iodization: country-wide data in school
      children from India.
AB  - OBJECTIVE: Country-wide evaluation of thyroid disorders in school children
      following two decades of universal salt iodization (USI) has not been carried out
      till date. This study was planned with aim to assess thyroid status of school
      children two decades after the launch of USI programme. DESIGN: Population
      survey. PATIENTS: We collected data from 25 schools in 19 cities across five
      different geographical zones of India. Those children who were evaluated for
      anthropometry, and goitre status by palpation formed 'total population'. Children
      who consented to give blood samples were defined as 'study population'.
      MEASUREMENTS: Serum free T3, free T4, TSH, anti-TPO antibody and thyroid
      ultrasound. RESULTS: A total of 38,961 children aged 5-15 years formed total
      population. Goitre rate was 15.5% while thyroid hypoechogenicity was found in
      4404 (11.3%) children. In the study population (13,790 children), 2258 (16.4%)
      had goitre, 505 (3.7%) had positive anti-TPO antibody titres, 1001 (7.3%) had
      hypothyroidism (TSH > 5.2 MUIU/ml) and 41 (0.3%) had thyrotoxicosis (TSH < 0.1
      MUIU/ml). Among goitrous children, 203 (9.0%) had anti-TPO positivity, 365
      (16.1%) had hypoechogenicity of thyroid and either of these were present in 488
      (21.6%) children. CONCLUSIONS: Endemic goitre in school children persisted
      nationwide, despite more than two decades of USI programme. Thyroid autoimmunity
      only partially explains the increase in goitre prevalence.

PMID- 22142265
TI  - Host and habitat specialization of avian malaria in Africa.
AB  - Studies of both vertebrates and invertebrates have suggested that specialists, as
      compared to generalists, are likely to suffer more serious declines in response
      to environmental change. Less is known about the effects of environmental
      conditions on specialist versus generalist parasites. Here, we study the
      evolutionary strategies of malaria parasites (Plasmodium spp.) among different
      bird host communities. We determined the parasite diversity and prevalence of
      avian malaria in three bird communities in the lowland forests in Cameroon,
      highland forests in East Africa and fynbos in South Africa. We calculated the
      host specificity index of parasites to examine the range of hosts parasitized as
      a function of the habitat and investigated the phylogenetic relationships of
      parasites. First, using phylogenetic and ancestral reconstruction analyses, we
      found an evolutionary tendency for generalist malaria parasites to become
      specialists. The transition rate at which generalists become specialists was
      nearly four times as great as the rate at which specialists become generalists.
      We also found more specialist parasites and greater parasite diversity in African
      lowland rainforests as compared to the more climatically variable habitats of the
      fynbos and the highland forests. Thus, with environmental changes, we anticipate
      a change in the distribution of both specialist and generalist parasites with
      potential impacts on bird communities.

PMID- 22142267
TI  - Urologic synechiae.
AB  - Synechiae are intracavitary adhesions; although rarely reported, they may occur
      within the urinary tract. They are well recognized within the gynecologic
      literature but are rarely reported as a cause of urologic pathology. We describe
      the endoscopic appearance of two such lesions, describing their pathologic role
      and the endoscopic management in two patients.

PMID- 22142269
TI  - Interplay between hydrodynamics and the free energy surface in the assembly of
      nanoscale hydrophobes.
AB  - Solvent plays an important role in the relative motion of nanoscopic bodies, and
      the study of such phenomena can help elucidate the mechanism of hydrophobic
      assembly, as well as the influence of solvent-mediated effects on in vivo motion
      in crowded cellular environments. Here we study important aspects of this problem
      within the framework of Brownian dynamics. We compute the free energy surface
      that the Brownian particles experience and their hydrodynamic interactions from
      molecular dynamics simulations in explicit solvent. We find that molecular scale
      effects dominate at short distances, thus giving rise to deviations from the
      predictions of continuum hydrodynamic theory. Drying phenomena, solvent layering,
      and fluctuations engender distinct signatures of the molecular scale. The rate of
      assembly in the diffusion-controlled limit is found to decrease from molecular
      scale hydrodynamic interactions, in opposition to the free energy driving force
      for hydrophobic assembly, and act to reinforce the influence of the free energy
      surface on the association of more hydrophilic bodies.

PMID- 22142268
TI  - Treating seeds with activators of plant defence generates long-lasting priming of
      resistance to pests and pathogens.
AB  - * Priming of defence is a strategy employed by plants exposed to stress to
      enhance resistance against future stress episodes with minimal associated costs
      on growth. Here, we test the hypothesis that application of priming agents to
      seeds can result in plants with primed defences. * We measured resistance to
      arthropod herbivores and disease in tomato (Solanum lycopersicum) plants grown
      from seed treated with jasmonic acid (JA) and/or beta-aminobutryric acid (BABA).
      * Plants grown from JA-treated seed showed increased resistance against herbivory
      by spider mites, caterpillars and aphids, and against the necrotrophic fungal
      pathogen, Botrytis cinerea. BABA seed treatment provided primed defence against
      powdery mildew disease caused by the biotrophic fungal pathogen, Oidium
      neolycopersici. Priming responses were long-lasting, with significant increases
      in resistance sustained in plants grown from treated seed for at least 8 wk, and
      were associated with enhanced defence gene expression during pathogen attack.
      There was no significant antagonism between different forms of defence in plants
      grown from seeds treated with a combination of JA and BABA. * Long-term defence
      priming by seed treatments was not accompanied by reductions in growth, and may
      therefore be suitable for commercial exploitation.

PMID- 22142270
TI  - Electrochemical modeling of the silica nanoparticle-biomembrane interaction.
AB  - The interaction of amorphous colloidal silica (SiO(2)) nanoparticles of well
      defined sizes with a dioleoyl phosphatidylcholine (DOPC) monolayer on a mercury
      (Hg) film electrode has been investigated. It was shown using electrochemical
      methods and microcalorimetry that particles interact with the monolayer, and the
      electrochemical data shows that the extent of interaction is inversely
      proportional to the particle size. Scanning electron microscopy (SEM) images of
      the electrode-supported monolayers following exposure to the particles shows that
      the nanoparticles bind to the DOPC monolayer irrespective of their size, forming
      a particle monolayer on the DOPC surface. A one-parameter model was developed to
      describe the electrochemical results where the fitted parameter is an interfacial
      layer thickness (3.2 nm). The model is based on the adsorptive interactions
      operating within this interfacial layer that are independent of the solution pH
      and solution ionic strength. The evidence implies that the most significant
      forces determining the interactions are van der Waals in character.

PMID- 22142271
TI  - In vivo skin treatment with tissue-tolerable plasma influences skin physiology
      and antioxidant profile in human stratum corneum.
AB  - The antimicrobial treatment of wounds is still a major problem. Tissue-tolerable
      electrical plasma (TTP) is a new approach for topical microbial disinfection of
      the skin surface. The aim of the present study was to investigate the influence
      of TTP on a carotenoid profile in relation to skin physiology parameters
      (epidermal barrier function, stratum corneum (SC) hydration, surface temperature
      and irritation parameters). We were interested in the interaction of TTP and the
      antioxidative network, as well as the consequences for skin physiology
      parameters. These parameters are also indicative of TTP safety in vivo. For
      plasma application, 'Kinpen 09' was used (surface exposure 30-43 degrees C) for 3
      s. Beta-carotene and water profiles were assessed by in vivo Raman
      microspectroscopy (skin composition analyzer 3510). Skin physiology parameters
      were measured with Tewameter TM 300, Corneometer CM 825, skin thermometer and
      Chromameter CR 300. All parameters were assessed non-invasively on seven healthy
      volunteers before and after plasma application in vivo. We could show that TTP
      application leads to a decrease in beta-carotene especially in the superficial
      SC. Skin-surface temperature increased by 1.74 degrees C, while the
      transepidermal water loss (TEWL) increase indicated an impaired barrier function.
      SC hydration decreased as seen in water profile especially in the superficial
      layers and capacitance values. A slight increase in skin redness was measurable.
      The induction of reactive oxygen species is probably the major contributor of TTP
      efficacy in skin disinfection. Skin physiology parameters were influenced without
      damaging the skin or skin functions, indicating the safety of TTP under in vivo
      conditions.

PMID- 22142272
TI  - Enhanced photoelectrochemical hydrogen production from silicon nanowire array
      photocathode.
AB  - Herein we report that silicon nanowires (SiNWs) fabricated via metal-catalyzed
      electroless etching yielded a photoelectrochemical hydrogen generation
      performance superior to that of a planar Si, which is attributed to a lower
      kinetic overpotential due to a higher surface roughness, favorable shift in the
      flat-band potential, and light-trapping effects of the SiNW surface. The SiNW
      photocathode yielded a photovoltage of 0.42 V, one of the highest values ever
      reported for hydrogen generation on p-type Si/electrolyte interfaces.

PMID- 22142273
TI  - Regional drug user services in times of scarce financial resources: using a rapid
      assessment response approach to evaluate, plan, and prioritize essential
      services.
AB  - The objective was to assess need, evaluate projects, and devise a roadmap for
      future provision given budget cuts. The analysis of 30 substance misuse services
      in towns and rural areas of Ireland was conducted in 2010. Analysis revealed that
      24,315 (95% CI 12,928-40,629) individuals were using illegal drugs in 2006, 893
      individuals were using opiates, opiate and cocaine use was increasing as was drug
      use amongst females. Evaluations demonstrated that not all services were meeting
      emerging needs, services lacked administrative support, and funding needed to be
      redirected. The RAR approach was useful for policy decisions and budget cuts in
      times of economic restraint.

PMID- 22142277
TI  - Can self-report questionnaires create illness cognitions in middle-aged men?
AB  - OBJECTIVE: To examine the effect of questionnaire context on self-reported
      illness cognition. DESIGN: A single-item measure of the perceived impact of lower
      urinary tract symptoms (LUTS) was embedded twice in a questionnaire battery
      completed by community-dwelling middle-aged males (N = 1,790). The impact measure
      was placed in two distinct questionnaire contexts; at the end of a general
      somatic symptoms questionnaire, and following an illness-specific symptoms
      questionnaire. The order of the two questionnaire contexts was counterbalanced in
      a random subsample. MAIN OUTCOME MEASURES: An established single-item measure of
      the perceived impact of LUTS. RESULTS: Concordance between the two single-item
      measures was moderate. Scores on a single-item measure of impact were
      significantly lower when assessed immediately following the completion of a LUTS
      specific questionnaire than when assessed following the completion of a general
      symptoms questionnaire. There was no evidence of order effects. The observed
      effect was moderated by the severity of LUTS such that the difference in
      perceived impact scores between contexts (where general symptoms context >
      illness-specific context) increased as urinary symptoms increased. CONCLUSION:
      Questionnaire context systematically influenced responses on self-report measures
      of illness impact. The magnitude of the context effect was largest in the highest
      quintile of LUTS severity, a difference of 0.5 on a scale with a range of 3.
      These findings may have implications for situations where patient reported
      outcome measures are used to evaluate health care interventions or inform
      treatment decisions.

PMID- 22142274
TI  - Geographical, temporal and racial disparities in late-stage prostate cancer
      incidence across Florida: a multiscale joinpoint regression analysis.
AB  - BACKGROUND: Although prostate cancer-related incidence and mortality have
      declined recently, striking racial/ethnic differences persist in the United
      States. Visualizing and modelling temporal trends of prostate cancer late-stage
      incidence, and how they vary according to geographic locations and race, should
      help explaining such disparities. Joinpoint regression is increasingly used to
      identify the timing and extent of changes in time series of health outcomes. Yet,
      most analyses of temporal trends are aspatial and conducted at the national level
      or for a single cancer registry. METHODS: Time series (1981-2007) of annual
      proportions of prostate cancer late-stage cases were analyzed for non-Hispanic
      Whites and non-Hispanic Blacks in each county of Florida. Noise in the data was
      first filtered by binomial kriging and results were modelled using joinpoint
      regression. A similar analysis was also conducted at the state level and for
      groups of metropolitan and non-metropolitan counties. Significant racial
      differences were detected using tests of parallelism and coincidence of time
      trends. A new disparity statistic was introduced to measure spatial and temporal
      changes in the frequency of racial disparities. RESULTS: State-level percentage
      of late-stage diagnosis decreased 50% since 1981; a decline that accelerated in
      the 90's when Prostate Specific Antigen (PSA) screening was introduced. Analysis
      at the metropolitan and non-metropolitan levels revealed that the frequency of
      late-stage diagnosis increased recently in urban areas, and this trend was
      significant for white males. The annual rate of decrease in late-stage diagnosis
      and the onset years for significant declines varied greatly among counties and
      racial groups. Most counties with non-significant average annual percent change
      (AAPC) were located in the Florida Panhandle for white males, whereas they
      clustered in South-eastern Florida for black males. The new disparity statistic
      indicated that the spatial extent of racial disparities reached a peak in 1990
      because of an early decline in frequency of late-stage diagnosis observed for
      black males. CONCLUSIONS: Analyzing temporal trends in cancer incidence and
      mortality rates outside a spatial framework is unsatisfactory, since it leads one
      to overlook significant geographical variation which can potentially generate new
      insights about the impact of various interventions. Differences observed among
      nested geographies in Florida show how the modifiable areal unit problem (MAUP)
      also impacts the analysis of temporal changes.

PMID- 22142278
TI  - Moderators of the mediated effect of intentions, planning, and saturated-fat
      intake in obese individuals.
AB  - OBJECTIVE: The present study aimed to advance our understanding of health-related
      theory, that is, the alleged intention-behavior gap in an obese population. It
      examined the mediating effects of planning on the intention-behavior relationship
      and the moderated mediation effects of age, self-efficacy and intentions within
      this relationship. METHOD: The study was conducted over a five-week period.
      Complete data from 571 obese participants were analyzed. The moderated mediation
      hypothesis was conducted using multiple-regression analysis. To test our
      theoretical model, intentions (Week 2), action self-efficacy (Week 2),
      maintenance self-efficacy (Week 5), planning (Week 5), and saturated-fat intake
      (Weeks 1 and 5) were measured by self-report. RESULTS: As hypothesized, planning
      mediated the intention-behavior relationship for perceived (two-item scale) and
      percentage-saturated-fat intake (measured by a food frequency questionnaire).
      Age, self-efficacy, and intention acted as moderators in the above mediation
      analysis. In specific, younger individuals, those with stronger intention, and
      people with higher levels of maintenance self-efficacy at higher levels of
      planning showed greater reductions in their perceived saturated-fat intake.
      CONCLUSIONS: For successful behavior change, knowledge of its mediators and
      moderators is needed. Future interventions targeting planning to change saturated
      fat intake should be guided by people's intentions, age, and self-efficacy
      levels.

PMID- 22142279
TI  - Cutaneous pseudolymphoma induced by Hirudo medicinalis therapy.

PMID- 22142280
TI  - Effects of hypodontia on craniofacial structures and mandibular growth pattern.
AB  - INTRODUCTION: This study was performed to examine craniofacial structures in
      persons with hypodontia and to reveal any differences, that may occur, when
      agenetic teeth are only found in the maxilla, the mandible or in both jaws. The
      groups consistent of 50 children (33 girls, 17 boys) aged between 9 and 13.5
      years were analyzed and assigned to three subgroups. Group 1 = upper jaw
      hypodontia. Group 2 = lower jaw hypodontia. Group 3 = hypodontia in both jaws.
      MATERIALS AND METHODS: Eleven angular and three index measurements from lateral
      encephalographs and two linear measurements from dental blaster casts were
      calculated. All data was statistically analyzed, parameters with p < 5% were
      investigated for each subgroup respectively. RESULTS: In comparison with
      standards the study group showed bimaxillary retrognathism and a reduction of the
      lower anterior facial height. Moreover both overbite and overjet significantly
      increased. Other values laid within the normal ranges. Evaluating results of the
      subgroups, differences in the means of SNA, SNB and overjet between the groups
      were observed.Analysis of the mandibular growth pattern revealed, that neither
      vertical nor horizontal patterns are dominant in hypodontia patients.
      CONCLUSIONS: In certain dentofacial parameters differences between persons with
      hypodontia and such with full dentition exist. According to our findings agenetic
      teeth may have a negative influence on the saggital development of a jaw and the
      lower face and may be responsible for increased overbites. This should receive
      attention in orthodontic treatment of hypodontia patients.

PMID- 22142281
TI  - Influence of water on anharmonicity, stability, and vibrational energy
      distribution of hydrogen-bonded adducts in atmospheric reactions: case study of
      the OH + isoprene reaction intermediate using ab initio molecular dynamics.
AB  - The effect of water on the stability and vibrational states of a hydroxy-isoprene
      adduct is probed through the introduction of 1-15 water molecules. It is found
      that when a static nuclear harmonic approximation is invoked there is a
      substantial red-shift of the alcohol O-H stretch (of the order of 800 cm(-1)) as
      a result of introduction of water. When potential energy surface sampling and
      associated anharmonicities are introduced through finite temperature ab initio
      dynamics, this hydroxy-isoprene OH stretch strongly couples with all the water
      vibrational modes as well as the hydroxy-isoprene OH bend modes. A new
      computational technique is introduced to probe the coupling between these modes.
      The method involves a two-dimensional, time-frequency analysis of the finite
      temperature vibrational properties. Such an analysis not only provides
      information about the modes that are coupled as a result of finite-temperature
      analysis, but also the temporal evolution of such coupling.

PMID- 22142282
TI  - Evidence for atypical auditory brainstem responses in young children with
      suspected autism spectrum disorders.
AB  - AIM:   The aim of this study was to characterize the auditory brainstem responses
      (ABRs) of young children with suspected autism spectrum disorders (ASDs) and
      compare them with the ABRs of children with language delay and with clinical
      norms. METHOD:   The ABRs of 26 children with suspected ASDs (21 males, five
      females; mean age 32.5 mo) and an age- and sex-matched group of 26 children with
      language delay (22 males, four females) were analysed. All children had normal
      hearing. The absolute latencies of waves I, III, and V, and interpeak latencies
      (IPLs) I to III, I to V, and III to V of the group with ASDs and the group with
      language delay were compared. Data from both groups were further compared with
      clinical norms. RESULTS:   All absolute latencies and IPLs were significantly
      prolonged in the group with suspected ASDs compared with the group with language
      delay, excluding IPL III-V (all p-values <0.05) and with clinical norms (all p
      values <0.001; IPL III-V, p<0.05). Significant prolongation of absolute and IPLs
      was also evident in the group with language delay compared with clinical norms,
      excluding IPL III to V (all p-values <0.001). The prevalence of abnormal findings
      in two or more absolute latencies was found to be significantly higher in the
      group with ASDs (50%) than in the group with language delay (8%; p=0.002).
      INTERPRETATION:   The results provide first-time evidence for a
      neurodevelopmental brainstem abnormality that is already apparent in young
      children with suspected ASD and language delay. The overlap in ABR findings
      supports the assertion that an auditory processing deficit may be at the core of
      these two disorders.

PMID- 22142283
TI  - Resection for hepatocellular carcinoma: is it justifiable to restrict this to the
      American Association for the Study of the Liver/Barcelona Clinic for Liver Cancer
      criteria?
AB  - Hepatocellular carcinoma (HCC) is an important cancer worldwide. The main
      curative treatment modality is surgical resection although only a minority of
      afflicted patients are amendable because of poor liver function reserve or
      extensive disease at the time of diagnosis. The selection criteria for surgical
      resection, however, are variable and frequently appear to be center-specific.
      Further, they are influenced by rapidly evolving data on the outcomes of surgical
      resection and other emerging modalities of treatment. Recently, two major
      international practice guidelines on the management of HCC were published at
      about the same time, namely those of the American Association for the Study of
      the Liver (AASLD), and of the Asia-Pacific Association for the Study of the Liver
      (APASL). These two practice guidelines differ significantly in philosophy and
      practice with regards to surgical resection. In fact, they reflect the two
      extremes of a spectrum of existing consensus opinions. The AASLD Guidelines have
      evolved from the guidelines of the Barcelona Clinic for Liver Cancer (BCLC), and
      are significantly more conservative with regard to surgical resection compared
      with the APASL Guidelines. The scientific basis for these major differences in
      criteria with regard to surgical resection for HCC is reviewed here, particularly
      with regard to the situation in the Asia-Pacific region where HCC is especially
      common.

PMID- 22142284
TI  - Bias in macrophage activation pattern influences non-alcoholic steatohepatitis
      (NASH) in mice.
AB  - In humans, there is large inter-individual variability in the evolution of NAFLD
      (non-alcoholic fatty liver disease) to NASH (non-alcoholic steatohepatitis). To
      investigate this issue, NASH was induced with an MCD (methionine-choline
      deficient) diet in C57BL/6 and Balb/c mice that are characterized by different
      biases in Th1/Th2 and macrophage (M1/M2) responses. Following 4 weeks on the MCD
      diet, steatosis and lobular inflammation were prevalent in C57BL/6 (Th1, M1
      oriented) than in Balb/c (Th2, M2 oriented) mice. Consistently, hepatic TNFalpha
      (tumour necrosis factor alpha) mRNA expression and circulating TNFalpha levels
      were higher in MCD-fed C57BL/6 than in MCD-fed Balb/c mice. The Th1/Th2 bias did
      not account for the increased NASH severity, as in both strains MCD feeding did
      not significantly modify the liver mRNA expression of the Th1 markers IFNgamma
      (interferon gamma) and T-bet or that of the Th2 markers IL-4 (interleukin 4) and
      GATA-3. Conversely, MCD-fed C57BL/6 mice displayed higher liver mRNAs for the
      macrophage M1 activation markers iNOS (inducible NO synthase), IL-12p40 and
      CXCL10 (CXC chemokine ligand 10) than similarly treated Balb/c mice, without
      effects on the M2 polarization markers IL-10 and MGL-1 (macrophage galactose-type
      C-type lectin-1). Circulating IL-12 was also higher in MCD-fed C57BL/6 than in
      MCD-fed Balb/c mice. The analysis of macrophages isolated from the livers of MCD
      fed animals confirmed an enhanced expression of M1 markers in C57BL/6 mice. Among
      all of the MCD-treated mice, liver iNOS, IL-12p40 and CXCL10 mRNA levels
      positively correlated with the frequency of hepatic necro-inflammatory foci. We
      concluded that the macrophage M1 bias in C57BL/6 mice may account for the
      increased severity of NASH in this strain, suggesting macrophage responses as
      important contributors to NAFLD progression.

PMID- 22142285
TI  - T. Philip Ayre and the T Piece.

PMID- 22142286
TI  - Design of novel FLT-3 inhibitors based on dual-layer 3D-QSAR model and fragment
      based compounds in silico.
AB  - FMS-like tyrosine kinase 3 (FLT-3) is strongly correlated with acute myeloid
      leukemia, but no FLT-3-inhibitor cocomplex structure is available to assist the
      design of therapeutic inhibitors. Hence, we propose a dual-layer 3D-QSAR model
      for FLT-3 that integrates the pharmacophore, CoMFA, and CoMSIA. We then coupled
      the model with the fragment-based design strategy to identify novel FLT-3
      inhibitors. In the first layer, the previously established model, Hypo02, was
      evaluated in terms of its correlation coefficient (r), RMS, cost difference, and
      configuration cost, with values of 0.930, 1.24, 106.45, and 16.44, respectively.
      Moreover, Fischer's cross-validation test of data generated by Hypo02 yielded a
      98% confidence level, and the validation of the testing set yielded a best r
      value of 0.87. The features of Hypo02 were separated into two parts and then used
      to screen the MiniMaybridge fragment compound database. Nine novel FLT-3
      inhibitors were generated in this layer. In the second layer, Hypo02 was
      subjected to an alignment rule to generate CoMFA- and CoMSIA-based models, for
      which the partial least-squares validation method was utilized. The values of
      q(2), r(2), and predictive r(2) were 0.58, 0.98, and 0.76, respectively, derived
      from the CoMFA model with steric and electrostatic fields. The CoMSIA model with
      five different fields yielded values of 0.54, 0.97, and 0.76 for q(2), r(2), and
      predictive r(2), respectively. The CoMFA and CoMSIA models were used to constrain
      3D structures of the nine novel FLT-3 inhibitors. This dual-layer 3D-QSAR model
      constitutes a valuable tool to easily and quickly screen and optimize novel
      potential FLT-3 inhibitors for the treatment of acute myeloid leukemia.

PMID- 22142287
TI  - The impact of vancomycin susceptibility on treatment outcomes among patients with
      methicillin resistant Staphylococcus aureus bacteremia.
AB  - BACKGROUND: Management of methicillin-resistant Staphylococcus aureus (MRSA)
      bacteremia remains a challenge. The emergence of MRSA strains with reduced
      vancomycin susceptibility complicates treatment. METHODS: A prospective cohort
      study (2005-2007) of patients with MRSA bacteremia treated with vancomycin was
      performed at an academic hospital. Vancomycin minimum inhibitory concentration
      (MIC) and minimum bactericidal concentration (MBC) were determined for stored
      MRSA isolates. Cox regression analysis was performed to predict 28-day all-cause
      mortality. RESULTS: One hundred sixty-three patients with MRSA bacteremia were
      evaluated. One hundred twelve patients (68.7%) had bacteremia due to MRSA with a
      vancomycin MIC >= 2 ug/mL. Among strains with a vancomycin MIC >= 2 ug/mL, 10
      isolates (8.9%) were vancomycin-intermediate S. aureus (VISA). Thirty-five
      patients (21.5%) died within 28 days after the diagnosis of MRSA bacteremia.
      Higher vancomycin MIC was not associated with mortality in this cohort [adjusted
      hazard ratio (aHR), 1.57; 95% confidence interval (CI), 0.73-3.37]. Vancomycin
      tolerance was observed in 4.3% (7/162) of isolates and was not associated with
      mortality (crude HR, 0.62; 95% CI, 0.08-4.50). Factors independently associated
      with mortality included higher age (aHR, 1.03; 95% CI 1.00-1.05), cirrhosis (aHR,
      3.01; 95% CI, 1.24-7.30), and intensive care unit admission within 48 hours after
      the diagnosis of bacteremia (aHR, 5.99; 95% CI, 2.86-12.58). CONCLUSIONS: Among
      patients with MRSA bacteremia treated with vancomycin, reduced vancomycin
      susceptibility and vancomycin tolerance were not associated with mortality after
      adjusting for patient factors. Patient factors including severity of illness and
      underlying co-morbidities were associated with the mortality.

PMID- 22142288
TI  - Tracking the metal of the goblins: cobalt's cycle of use.
AB  - Cobalt is a vital element in many technological applications, which, together
      with its increasing end-use in batteries, makes it important to quantify its
      cycle of use. We have done so for the planet as a whole and for the three
      principal cobalt-using countries -  China, Japan, and the United States - for
      2005. Together, China, Japan, and the United States accounted for approximately
      65% of the cobalt fabricated and manufactured into end-use products (a total of
      37 Gg Co). A time residence model allowed calculations of in-use stock
      accumulation and recycled and landfilled flows. China had the largest
      accumulation of in-use stock at some 4.3 Gg Co, over half of which was comprised
      of consumer battery stock. More than half of the stock accumulation in the United
      States was estimated to be in aircraft, rocket, and gas turbine engines, with a
      total in-use stock accumulation of approximately 3 Gg Co. The largest amounts of
      cobalt landfilled in China, the United States, and the planet were from the
      "chemical and other uses" category, and Japan's largest landfilled flow was in
      consumer batteries.

PMID- 22142290
TI  - "Branding" your practice: ethics and excellence.

PMID- 22142289
TI  - A systematic review of the effects of pharmacological agents on walking function
      in people with spinal cord injury.
AB  - Studies of spinalized animals indicate that some pharmacological agents may act
      on receptors in the spinal cord, helping to produce coordinated locomotor
      movement. Other drugs may help to ameliorate the neuropathological changes
      resulting from spinal cord injury (SCI), such as spasticity or demyelination, to
      improve walking. The purpose of this study was to systematically review the
      effects of pharmacological agents on gait in people with SCI. A keyword
      literature search of articles that evaluated the effects of drugs on walking
      after SCI was performed using the databases MEDLINE/PubMed, CINAHL, EMBASE,
      PsycINFO, and hand searching. Two reviewers independently evaluated each study,
      using the Physiotherapy Evidence Database (PEDro) tool for randomized clinical
      trials (RCTs), and the modified Downs & Black scale for all other studies.
      Results were tabulated and levels of evidence were assigned. Eleven studies met
      the inclusion criteria. One RCT provided Level 1 evidence that GM-1 ganglioside
      in combination with physical therapy improved motor scores, walking velocity, and
      distance better than placebo and physical therapy in persons with incomplete SCI.
      Multiple studies (levels of evidence 1-5) showed that clonidine and
      cyproheptadine may improve locomotor function and walking speed in severely
      impaired individuals with incomplete SCI. Gains in walking speed associated with
      GM-1, cyproheptadine, and clonidine are low compared to those seen with locomotor
      training. There was also Level 1 evidence that 4-aminopyridine and L-dopa were no
      better than placebo in helping to improve gait. Two Level 5 studies showed that
      baclofen had little to no effect on improving walking in persons with incomplete
      SCI. There is limited evidence that pharmacological agents tested so far would
      facilitate the recovery of walking after SCI. More studies are needed to better
      understand the effects of drugs combined with gait training on walking outcomes
      in people with SCI.

PMID- 22142291
TI  - Treatment planning challenges in the maxillary anterior region consequent to
      severe loss of buccal bone.
AB  - The burgeoning popularity of dental implant usage in the maxillary anterior
      region is well recognized. On the other hand, challenges involved in achieving
      optimal esthetics through implants have also been discussed extensively. Presence
      of labial/buccal bone in the maxillary anterior region is necessary for esthetic
      success of treatment, with or without the use of dental implants. This case
      report describes the multidisciplinary management of a rare case with severe loss
      of buccal bone confined to the maxillary central incisor region. A patient with a
      recent history of orthodontic treatment presented with a large buccal dehiscence
      of soft tissue that exposed nearly the entire buccal root surface of both
      maxillary central incisors. The treatment plan included extraction of both
      central incisors, hard and soft tissue ridge augmentation, and an all-ceramic
      fixed partial denture. After 2 years in function, the condition of soft tissues
      and integrity of the restorations remained stable. A discussion of traditional
      versus contemporary treatment planning using dental implants in such situations
      is presented. CLINICAL SIGNIFICANCE: Although implant therapy has proven to be a
      highly successful option, traditional treatment without implants may be
      advantageous in certain clinical situations. Compared to implant therapy, it can
      provide similar or better esthetic results with reduced treatment procedures,
      expenses, and time.

PMID- 22142292
TI  - COMMENTARY. Treatment planning challenges in the maxillary anterior region
      consequent to severe loss of buccal bone.

PMID- 22142293
TI  - Emergence angles of the cementoenamel junction in natural maxillary anterior
      teeth.
AB  - STATEMENT OF THE PROBLEM:   Fabrication of normal crown contour to maintain
      gingival health is difficult in the absence of emergence angle data. PURPOSE:  
      The aim of this study was to measure the geometric values of the emergence angles
      on the cementoenamel junction (CEJ) for natural maxillary anterior teeth.
      MATERIAL AND METHODS:   This study collected 148 natural permanent maxillary
      anterior teeth (74 central incisors, 59 lateral incisors, and 15 canines) with
      intact cervixes for this study. The teeth were scanned with a three-dimensional
      (3D) scanner to construct 3D models. This study measured the emergence angles of
      the cervical CEJ on the zenith of labial, palatal, mesial, and distal, for each
      tooth. RESULTS:   Measurements made on 148 maxillary anterior teeth showed the
      emergence angle to be within a narrow range from 11.30 degrees  to 15.26 degrees
      , irrespective of the tooth location. There were no statistically significant
      differences between any two groups (p > 0.05). CONCLUSIONS:   On the basis of
      measurements taken from natural teeth, we conclude that the emergence angles of
      the CEJ in natural maxillary anterior teeth should be 15 degrees  from the root
      surface. CLINICAL SIGNIFICANCE: The information presented in this article may be
      useful in helping to create dental restorations with optional emergence angles
      over the CEJ in natural maxillary anterior teeth. Prior to the treatment the
      dentist should consider not only the fit of the crown, but also the emergence
      angles and contours of the soft tissues surrounding the involved teeth.

PMID- 22142294
TI  - COMMENTARY. Emergence angles of the cementoenamel junction in natural maxillary
      anterior teeth.

PMID- 22142295
TI  - Color management of the cervical region using different framework materials.
AB  - BACKGROUND:   Color-matching of the cervical area between natural teeth and
      different crown prostheses is a common clinical problem. PURPOSE:   The purpose
      of this study was to compare the color of the cervical region of five
      commercially available crown systems to an extracted natural tooth and to each
      other. MATERIALS AND METHODS:   The color of the cervical region of an extracted
      maxillary incisor was measured by means of a colorimeter (ShadeVision, X-Rite).
      Fifty master dies were fabricated, divided into five groups (N=10) according to
      the framework material; group 1: high-noble gold alloy, group 2: same as group 1
      but treated with gold paste material, group 3: precious reinforced alloy, group
      4: white zirconium oxide substructure (Lava 3M ESPE), and group 5: shaded
      zirconium oxide (Lava). A direct comparison of L*, a*, and b* parameters was
      accomplished between the control natural tooth and the five crown systems, and
      the mean color differences (DeltaE) was calculated. The data were statistically
      analyzed with one-way analysis of variance and post hoc multiple comparison
      (alpha=0.05). RESULTS:   Compared to the natural tooth, the mean color
      differences (DeltaE) values were clinically unacceptable for all groups (DeltaE >
      3.7). The detected color differences, among different porcelain systems, were not
      visually perceptible (DeltaE < 3.7). CONCLUSIONS:   Within the limitations of
      this study, the cervical color of an extracted natural tooth could not be
      duplicated using different crowns systems. CLINICAL SIGNIFICANCE: Color-matching
      of the cervical region of different crown systems with natural tooth remains a
      difficult task.

PMID- 22142296
TI  - COMMENTARY. Color management of the cervical region using different framework
      materials.

PMID- 22142297
TI  - The effects of different desensitizing agents on the shear bond strength of
      adhesive resin cement to dentin.
AB  - STATEMENT OF THE PROBLEM:   The choice of desensitizing agent can affect the bond
      strength of adhesive resin cement to dentin. PURPOSE:   The purpose of this study
      was to evaluate the effects of different dentin desensitizing agents on the bond
      strength of adhesive resin cement to dentin. MATERIALS AND METHODS:   Sixty
      specimen teeth were randomly divided into six groups (n=10). Five groups of teeth
      were treated with a desensitizing agent containing sodium and calcium fluoride in
      cellulose alone, hydroxyethyl methacrylate (HEMA), benzalkonium chloride and
      sodium fluoride, HEMA and glutaraldehyde, an ormocer-based or a resin-based
      dentin desensitizer. The remaining 10 specimens served as controls. Adhesive
      resin cement was applied to the dentin surface. The shear bond strength was
      measured using a universal testing machine at a 0.5 mm/minute crosshead speed.
      The data were analyzed statistically with one-way analysis of variance and a
      Tukey's Honestly Significant Difference (HSD) test (alpha=0.05). In addition,
      dentin surfaces were examined by a scanning electron microscope. RESULTS:   THE
      lowest bond strength was in the group treated with desensitizing agent containing
      sodium and calcium fluoride and the highest bond strength was from the group
      treated with desensitizing agent containing HEMA and sodium fluoride.
      CONCLUSIONS:   Desensitizing agents containing sodium and calcium fluoride
      reduced the bond strength of adhesive resin cement. CLINICAL SIGNIFICANCE: The
      type of desensitizer used is an important factor regarding the bond strength of
      adhesive resin cements to dentin.

PMID- 22142298
TI  - COMMENTARY. The effects of different desensitizing agents on the shear bond
      strength of adhesive resin cement to dentin.

PMID- 22142299
TI  - Enamel and dentin bond strengths of a new self-etch adhesive system.
AB  - statement of problem:  Self-etch adhesives typically are mildly acidic and
      therefore less effective than etch-and-rinse adhesives for bonding to enamel.
      PURPOSE:   The purpose of this study was to evaluate the enamel and dentin shear
      bond strengths of a new two-step self-etch adhesive system, OptiBond XTR (Kerr
      Corporation, Orange, CA, USA). MATERIALS AND METHODS:   The labial surfaces of 80
      bovine teeth were ground to create flat, 600-grit enamel or dentin surfaces.
      Composite was bonded to enamel or dentin using the new two-step self-etch system
      or a three-step etch-and-rinse (OptiBond FL, Kerr), two-step self-etch (Clearfil
      SE Bond, Kuraray America, Houston, TX, USA), or one-step self-etch adhesive (Xeno
      IV, Dentsply Caulk, Milford, DE, USA). Following storage in water for 24 hours,
      shear bond strengths were determined using a universal testing machine. The
      enamel and dentin data sets were subjected to separate analysis of variance and
      Tukey's tests. Scanning electron microscopy was used to evaluate the effects of
      each system on enamel. RESULTS:   Mean shear bond strengths to enamel ranged from
      18.1 MPa for Xeno IV to 41.0 MPa for OptiBond FL. On dentin, the means ranged
      from 33.3 MPa for OptiBond FL to 47.1 MPa for Clearfil SE Bond. OptiBond XTR
      performed as well as Clearfil SE Bond on dentin and as well as OptiBond FL on
      enamel. Field emission scanning electron microscope revealed that OptiBond XTR
      produced an enamel etch pattern that was less defined than that of OptiBond FL
      (37.5% phosphoric acid) but more defined than that of Clearfil SE Bond or Xeno
      IV. CONCLUSION:   The new two-step self-etch adhesive system formed excellent
      bonds to enamel and dentin in vitro. CLINICAL SIGNIFICANCE: OptiBond XTR, a new
      two-step self-etch adhesive system, is a promising material for bonding to enamel
      as well as to dentin.

PMID- 22142300
TI  - COMMENTARY. Enamel and dentin bond strengths of a new self-etch adhesive system.

PMID- 22142301
TI  - Influence of activated bleaching on various adhesive restorative systems.
AB  - STATEMENT OF THE PROBLEM:   When adhesive restorations are used in combination
      with bleaching in clinical applications, it is generally recommended to wait for
      a period of time between the two procedures. However, it is not clear if a time
      interval is necessary between applying the bleaching treatments and the silorane
      based restorative system. PURPOSE:   The purpose of this in vitro study was to
      determine if activated bleaching affects the bond strength of silorane-based
      restorative, a newly developed restorative that uses a polymerization system that
      has been reported to be insensitive to oxygen. METHODS:   A gel consisting of 38%
      hydrogen peroxide was applied to ground labial enamel surfaces and activated
      using a diode laser to bleach the teeth. Then, without waiting for any period of
      time, four different restorative materials were applied to the bleached enamel
      surfaces, and these sets were compared with nonbleached control samples. The
      shear bond strength of the restorative systems to enamel was tested, and data was
      evaluated using two-way analysis of variance and Tukey HSD tests. RESULTS:  
      Significant differences (p<0.05) in shear bond strengths were found among
      bleached and nonbleached enamel surfaces. CONCLUSION:   It may be more beneficial
      to allow a time interval of 2 to 3 weeks between activated hydrogen peroxide
      bleaching and applying silorane-based composite restoratives or methacrylate
      based composites than just applying restorative agents immediately after
      bleaching. However, further studies are needed to examine the structural effects
      of activated hydrogen peroxide on enamel. CLINICAL SIGNIFICANCE: A time interval
      should be allowed between the application of silorane-based or methacrylate-based
      restorations and activated hydrogen peroxide bleaching systems.

PMID- 22142302
TI  - COMMENTARY. Influence of activated bleaching on various adhesive restorative
      systems.

PMID- 22142303
TI  - Critical appraisal. Current usage of glutaraldehyde/HEMA.
AB  - The use of glutaraldehyde/2-hydroxyethylmethacrylate (HEMA) combinations has been
      recommended for routine use in restorative dentistry by many authors and opinion
      leaders. Clinical restorative sites are colonized by bacteria that can contribute
      to postoperative sensitivity or recurrent caries. The structure of dentin allows
      for fluid conductance, which has been identified by Brannstrom as the cause of
      dentin sensitivity and as well, its water content challenges short- and long-term
      adhesion. The glutaraldehyde/HEMA combination is stated to be antimicrobial, a
      flocculating agent that strengthens collagen, and an agent that can create
      tubular occlusion, thereby reducing postoperative sensitivity by limiting fluid
      movement without affecting the strength of bonding or adhesive cements. This
      Critical Appraisal reviews five publications that deal with the various issues
      and clinical challenges described above, and provides suggestions for additional
      reading. A Bottom Line summary is provided.

PMID- 22142304
TI  - Ferroelectricity and pressure-induced phenomena driven by neutral ionic valence
      instability of acid-base supramolecules.
AB  - Supramolecular ferroelectric cocrystals of phenazine (Phz) with chloranilic acid
      (H(2)ca), bromanilic acid (H(2)ba), and fluoranilic acid (H(2)fa) have been
      characterized by the interplay between their structural transformations and solid
      state acid-base (proton transfer) reactions. At ambient pressure, the Phz-H(2)ca,
      Phz-H(2)ba, and their deuterated crystals exhibit incomplete proton displacement,
      which transforms the neutral molecules into semi-ionic at low temperatures below
      the Curie point (T(c)(IC) < T < T(c)(I)). For the cocrystal of the less acidic
      H(2)fa, the ferroelectric phase is induced only by applying hydrostatic pressure
      above ~0.6 GPa. According to the combined studies of temperature-dependent
      dielectric permittivity and synchrotron X-ray diffraction, it was proved that the
      ferroelectric (FE-I) phase is always accompanied at lower temperatures by
      successive phase transitions to the lattice modulated phases with incommensurate
      periodicities (IC phase, T(c)(II) < T < T(c)(IC)) and with commensurate (2- or 3
      fold) periodicities (FE-II or FE-III phase, T < T(c)(II)). Whereas the ground
      state structures at ambient pressure are different from one another among the Phz
      H(2)ca (FE-II form), Phz-H(2)ba (FE-III form), and Phz-H(2)fa (paraelectric
      form), their systematic changes under pressure depict a universal pressure
      temperature phase diagram. The possible origins of structural changes are
      assigned to the valence instability and the frustrated Coulomb interactions that
      induce the charge disproportionation (coexisting neutral ionic) states with the
      staging spatial orders.

PMID- 22142305
TI  - Catalysis-based inhibitors of the calcium signaling function of CD38.
AB  - CD38 is a signaling enzyme responsible for catalyzing the synthesis of cyclic ADP
      ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate; both are
      universal Ca(2+) messenger molecules. Ablation of the CD38 gene in mice causes
      multiple physiological defects, including impaired oxytocin release, that result
      in altered social behavior. A series of catalysis-based inhibitors of CD38 were
      designed and synthesized, starting with arabinosyl-2'-fluoro-2'-deoxynicotinamide
      mononucleotide. Structure-function relationships were analyzed to assess the
      structural determinants important for inhibiting the NADase activity of CD38. X
      ray crystallography was used to reveal the covalent intermediates that were
      formed with the catalytic residue, Glu226. Metabolically stable analogues that
      were resistant to inactivation by phosphatase and esterase were synthesized and
      shown to be effective in inhibiting intracellular cADPR production in human HL-60
      cells during induction of differentiation by retinoic acid. The inhibition was
      species-independent, and the analogues were similarly effective in blocking the
      cyclization reaction of CD38 in rat ventricular tissue extracts, as well as
      inhibiting the alpha-agonist-induced constriction in rat mesentery arteries.
      These compounds thus represent the first generally applicable and catalysis-based
      inhibitors of the Ca(2+) signaling function of CD38.

PMID- 22142306
TI  - Gene expression is differently affected by pimecrolimus and betamethasone in
      lesional skin of atopic dermatitis.
AB  - BACKGROUND: Topical corticosteroids and calcineurin inhibitors are well-known
      treatments of atopic dermatitis (AD) but differ in their efficacy and side
      effects. We recently showed that betamethasone valerate (BM) although clinically
      more efficient impaired skin barrier repair in contrast to pimecrolimus in AD.
      OBJECTIVE: This study elucidates the mode of action of topical BM and
      pimecrolimus cream in AD. METHODS: Lesional AD skin samples after topical
      treatment with either BM or pimecrolimus were subjected to gene expression
      profile analysis. RESULTS: Betamethasone valerate resulted in a significant
      reduction in mRNA levels of genes encoding markers of immune cells and
      inflammation, dendritic cells, T cells, cytokines, chemokines, and serine
      proteases, whereas pimecrolimus exerted minor effects only. This corroborates the
      clinical finding that BM reduces inflammation more effectively than pimecrolimus.
      Genes encoding molecules important for skin barrier function were differently
      affected. Both BM and pimecrolimus normalized the expression of filaggrin and
      loricrin. BM, but not pimecrolimus, significantly reduced the expression of rate
      limiting enzymes for lipid synthesis and the expression of involucrin and small
      proline-rich proteins, which covalently bind ceramides. This may explain the lack
      of restoration of functional stratum corneum layers observed after BM treatment.
      CONCLUSION: The gene expression profiles are consistent with our previous
      findings that corticosteroids may exert a more potent anti-inflammatory effect
      but may impair the restoration of the skin barrier. Corticosteroids are still the
      main treatment for severe and acutely exacerbated AD; pimecrolimus may be
      preferable for long-term treatment and stabilization.

PMID- 22142307
TI  - Crosstalk and barriers between the electron carriers of the endoplasmic
      reticulum.
AB  - SIGNIFICANCE: The lumen of the endoplasmic reticulum (ER) constitutes a separate
      compartment with a special proteome and metabolome. The characteristic redox
      environment required for the optimal functioning of local pathways is defined by
      the redox couples of the main electron carriers. These molecules, glutathione,
      pyridine nucleotides, and ascorbic acid, are present within the ER, but their
      composition, concentration, and redox state are characteristically different from
      those observed in other subcellular compartments. Spatial and kinetic barriers
      contribute to the generation and maintenance of this special redox environment.
      RECENT ADVANCES: The ER redox has usually been considered from the perspective of
      oxidative protein folding, one of the major functions of the ER. Thus, the lumen
      has been described as a relatively oxidizing subcellular compartment. CRITICAL
      ISSUES: The ER redoxome has been scantily mapped. However, recent observations
      suggest that the redox systems in reduced and oxidized states are present
      simultaneously. The concerted actions of transmembrane uptake processes and local
      oxidoreductases as well as the absence of specific transport and enzyme
      activities maintain the oxidized state of the thiol-disulfide systems and the
      reduced state of the pyridine nucleotide redox systems. These states are
      prerequisites for the normal redox reactions localized in the ER. FUTURE
      DIRECTIONS: An outline of the interactions between the major electron carriers of
      the ER will contribute to a better understanding of human diseases related to ER
      redox homeostasis.

PMID- 22142308
TI  - Comprehensive solid-state NMR analysis reveals the effects of N-methylation on
      the molecular dynamics of glycine.
AB  - Molecular dynamics of metabolites are important for their interactions and
      functions. To understand the structural dependence of molecular dynamics for N
      methylated glycines, we comprehensively measured the (13)C and (1)H spin-lattice
      relaxation times for sarcosine, N,N-dimethylglycine, betaine, and betaine
      hydrochloride over a temperature range of 178-460 K. We found that the
      reorientations of methyl groups were observed for all these molecules, whereas
      reorientations of whole trimethylamine groups were detected in betaines. While
      similar rotational properties were observed for methyl groups in N,N
      dimethylglycine and those in betaine, three methyl groups in betaine
      hydrochloride had different motional properties (E(a) ~ 20.5 kJ/mol, tau(0) ~
      1.85 * 10(-13) s; E(a) ~ 13.9 kJ/mol, tau(0) ~ 2.1 * 10(-12) s; E(a) ~ 15.8
      kJ/mol, tau(0) ~ 1.1 * 10(-12) s). N,N-Dimethylglycine showed a phase transition
      at 348.5 K with changed relaxation behavior for methyl groups showing distinct
      E(a) and tau(0) values. The DIPSHIFT experiments showed that CH(3) and CH(2)
      moieties in these molecules had dipolar-dephasing curves similar to these
      moieties in alanine and glycine. The activation energies for CH(3) rotations
      positively correlated with the number of substituted methyl groups. These
      findings provided useful information for the structural dependence of molecular
      dynamics for N-methylated glycines and demonstrated solid-state NMR as a useful
      tool for probing the structure-dynamics relationships.

PMID- 22142309
TI  - Modulation of skin pigmentation by the tetrapeptide PKEK: in vitro and in vivo
      evidence for skin whitening effects.
AB  - Uneven skin pigmentation is a significant cosmetic concern, and the
      identification of topically applicable molecules to address this issue is of
      general interest. We report that the tetrapeptide PKEK (Pro-Lys-Glu-Lys) can
      exert skin whitening effects based on one in vitro and four double-blinded
      vehicle-controlled in vivo studies. (i) Treatment of human keratinocytes with
      PKEK significantly reduced UVB-stimulated mRNA expression of interleukin (IL)-6,
      IL-8 and TNF-alpha and, most importantly, proopiomelanocorticotropin (POMC), i.e.
      a gene encoding the pigmentation-inducing soluble mediator alpha- (alpha-MSH).
      (ii) PKEK treatment significantly inhibited UVB-induced upregulation of genes
      encoding for IL-1alpha, IL-6, IL-8, TNF-alpha as well as POMC and tyrosinase in
      10 healthy volunteers pretreated with PKEK for 4 weeks once daily. (iii) In a
      study enrolling 39 Caucasian women, facial pigment spots significantly faded
      after 6 weeks when PKEK was combined with the skin whitener sodium ascorbyl
      phosphate (SAP), whereas PKEK or SAP alone led to less pronounced fading of the
      pigment spots. (iv) Addition of PKEK enhanced the skin whitening potency of a SAP
      containing preparation if applied for 8 weeks to the back of hands of 19
      Caucasians. (v) 27 Japanese women were treated on their faces twice daily with an
      SAP only or a PKEK+SAP-containing formulation for 8 weeks. Application of
      PKEK+SAP significantly reduced skin pigmentation by 26% and by 18% according to
      SCINEXA score. We demonstrate that PKEK has the capacity to reduce UVB-induced
      skin pigmentation and may be suited to serve as a skin tone-modulating agent in
      cosmetic products.

PMID- 22142310
TI  - The solution growth of copper nanowires and nanotubes is driven by screw
      dislocations.
AB  - Copper (Cu) nanowires (NWs) are inexpensive conducting nanomaterials intensively
      explored for transparent conducting electrodes and other applications. However,
      the mechanism for solution growth of Cu NWs remains elusive so far. Here we show
      that the one-dimensional anisotropic growth of Cu NWs and nanotubes (NTs) in
      solution is driven by axial screw dislocations. All three types of evidence for
      dislocation-driven growth have been conclusively observed using transmission
      electron microscopy (TEM) techniques: rigorous two-beam TEM analysis that
      conclusively characterizes the dislocations in the NWs to be pure screw
      dislocations along <110> direction, twist contour analysis that confirms the
      presence of Eshelby twist associated with the dislocation, and the observation of
      spontaneously formed hollow NTs. The reduction-oxidation (redox) electrochemical
      reaction forming the Cu NWs presents new chemistry for controlling
      supersaturation to promote dislocation-driven NW growth. Using this understanding
      to intentionally manipulate the supersaturation, we have further improved the NW
      growth by using a continuous flow reactor to yield longer Cu NWs under much
      milder chemical conditions. The rational synthesis of Cu NWs with control over
      size and geometry will facilitate their applications.

PMID- 22142311
TI  - Nerve mapping for prostatectomies: novel technologies under development.
AB  - Prostatic neuroanatomy is difficult to visualize intraoperatively and can be
      extremely variable. Damage to these nerves during prostatectomies may lead to
      postoperative complications such as erectile dysfunction and incontinence. This
      review aims to discuss the prostatic neuroanatomy, sites of potential nerve
      damage during a prostatectomy, and nerve-mapping technologies being developed to
      prevent neural injury. These technologies include stimulation, dyes, and direct
      visualization. Nerve stimulation works by testing an area and observing a
      physiologic response but is limited by the long half-life for an erectile
      response; examples include CaverMap, ProPep, and optical nerve stimulation. Few
      nerve dyes have been approved by the Food and Drug Administration (FDA) because
      of the extensive testing required; examples of nerve dyes include compounds from
      Avelas and General Electric, fluorescent cholera toxin subunit B, indocyanine
      green, fluorescent inactivated herpes simplex 2, and Fluoro-Gold. Direct
      visualization techniques have a simpler FDA approval process; examples include
      optical coherence tomography, multiphoton microscopy, ultrasound, coherent anti
      Stokes Raman scattering. Many researchers are developing several novel
      technologies that can be categorized as stimulation based, dye-based, or direct
      visualization. As of yet, none has shown clear evidence to improve surgical
      outcomes and consequently lack wide adoption. Further development of these
      technologies may lead to improved complication rates after prostatectomies.
      Clinically, some technologies have demonstrated utility in predicting the
      development of complications. By using that information, more aggressive
      rehabilitation programs may lead to improved long-term function. These
      technologies can also be applied for research to improve our knowledge of the
      neuroanatomy and physiology of erection and incontinence.

PMID- 22142312
TI  - Systems medicine and metabolic modelling.
AB  - Several complex diseases are caused by the malfunction of human metabolism, and
      deciphering the underlying molecular mechanisms can elucidate their aetiology.
      Systems biology is an integrative approach combining experimental and
      computational biology to identify and describe the molecular mechanisms of
      complex biological systems. Systems medicine has the potential to elucidate the
      onset and progression of complex metabolic diseases through the use of
      computational approaches. Advances in biotechnology have resulted in the
      provision of high-throughput data, which provide information about different
      metabolic processes. The systems medicine approach can utilize such data to
      reconstruct genome-scale metabolic models that can be used to study the function
      of specific enzymes and pathways in the context of the complete metabolic
      network. In this review, we outline the importance of genome-scale models in
      systems medicine and discuss how they may contribute towards the development of
      personalized medicine.

PMID- 22142313
TI  - Beyond core measures: identifying modifiable risk factors for prevention of
      surgical site infection after elective total abdominal hysterectomy.
AB  - BACKGROUND: Despite adherence to the Centers for Medicare and Medicaid Services
      (CMS) core measures for preventing surgical site infections (SSI), our
      institution has a >10% rate of SSI after total abdominal hysterectomy (TAH),
      higher than the 90(th) percentile for SSI rates published in the 2009 National
      Healthcare Safety Network report. METHODS: A retrospective chart review was
      performed for patients who underwent elective TAH at a public safety net hospital
      in Denver from December 30, 2005, to March 9, 2010. The primary outcome was
      development of SSI within 30 days. A secondary outcome was adherence to CMS core
      measures. RESULTS: A total of 192 patients were included in the analysis, of whom
      21 (10.9%) developed SSI. More than 95% had received antibiotics in the 60 min
      before surgical incision, and >90% received an appropriate antibiotic. Compliance
      with post-anesthesia care unit normothermia was equivalent in the SSI and non-SSI
      groups (81.0% vs. 75.2%; p=0.5588). Surgical site infection was associated with
      obesity (body mass index [BMI]>=30) (15.4% vs. 6.9%; p=0.0609), estimated blood
      loss>=500 mL (18.5% vs. 8.0%; p=0.0353), and receipt of a blood transfusion
      (28.6% vs. 10.5%; p=0.0183). In a multiple logistic regression model, obesity
      marginally increased the risk of SSI (odds ratio [OR] 2.55; 95% confidence
      interval [CI] 0.94-6.74), whereas blood transfusion was significantly associated
      with a higher risk of SSI (OR 3.58; 95% CI 1.21-10.62). CONCLUSIONS: Blood
      transfusion was associated with SSI after TAH in our population. As it is a
      modifiable risk factor, larger multi-center studies are needed to confirm this
      result and determine appropriate transfusion thresholds.

PMID- 22142314
TI  - Surgical site infections after abdominal closure in colorectal surgery using
      triclosan-coated absorbable suture (PDS Plus) vs. uncoated sutures (PDS II): a
      randomized multicenter study.
AB  - BACKGROUND: Surgical site infections (SSI) are the third most common hospital
      acquired infections and account for 14% to 16% of all such infections. In
      elective colorectal operations, the international SSI rate ranges from 4.7%-25%.
      In a previous retrospective study in this department, the SSI rate was
      unacceptably high (25%), and the promising different international evaluations of
      triclosan-coated suture materials encouraged us to create a multicenter
      randomized trial to improve our results. The main goal of this study was to
      compare triclosan-coated and uncoated absorbable suture (PDS Plus((r)) with PDS
      II((r))) in elective colorectal operations. METHODS: This was an internet-based
      study involving seven surgical centers. All the elective colorectal operations
      were performed by experienced surgeons. For abdominal fascia closure, running
      looped PDS was applied; triclosan-coated or uncoated PDS was chosen by computer
      randomization. Pre-operative and peri-operative variables such as gender, body
      mass index, neoadjuvant therapy, type II diabetes mellitus, amount of wound
      dressing material used, nursing days, and microbiological results were recorded.
      After the operation, the patient's data and risk factors were collected in a
      password-protected online database. RESULTS: From 485 patients randomized, SSI
      was documented in 47 patients (12.5%), 23 (12.2%) in the group having triclosan
      coated sutures (n=188) and 24 (12.2%) in the uncoated suture group (n=197), a non
      significant difference. Of all SSIs, 13 (27.7%) were diagnosed only after
      discharge, being recognized in the outpatient setting, with four patients in the
      triclosan suture group (8.5%) and nine in the uncoated suture group (19.2%) being
      affected with no significant differences in the demographic data. Microbiological
      examinations, in addition to the same colon flora in both groups, revealed two
      gram-positive infections in the uncoated suture group. The hospital stay and
      costs of dressings were significantly higher in patients having SSIs. CONCLUSION:
      Compared with the previous retrospective studies of this department, the
      implementation of looped PDS decreased the incidence of SSI by one-half, whether
      the suture was triclosan-coated or not. It seems that patient factors are less
      important than operative factors in the occurrence of SSI, and there were no
      differences between elective colon and rectal operations in the development of
      incisional infections. No beneficial effect of triclosan against gram-positive
      bacteria, which has been reported in the literature, could be confirmed in our
      study. We could not show an effect against gram-negative enteric microorganisms.
      Higher additional costs and longer hospital stay with SSI were confirmed.

PMID- 22142315
TI  - Acute scrotum caused by sigmoid diverticulitis.
AB  - BACKGROUND: Abscesses are one of many complications of diverticulitis and can be
      found intra-abdominally or in the pelvis. METHODS: Case report and review of the
      pertinent English-language literature. RESULTS: We describe an unusual
      presentation of a diverticular abscess, tracking down the inguinal canal and
      causing acute scrotum possibly secondary to a hernia. CONCLUSION: A deviation
      from the usual clinical presentation of diverticulitis should prompt the
      physician to obtain further radiologic evaluation. Computed tomography scanning
      is recommended, especially when an abscess is suspected.

PMID- 22142316
TI  - Selection of prophylactic antimicrobial agent may affect incidence of infection
      in small bowel and colorectal surgery.
AB  - BACKGROUND: Antibiotic prophylaxis guidelines suggest single-dose regimens are
      adequate, but comparisons of multiple agents are lacking. We compared post
      operative infection rates retrospectively among six common prophylactic agents
      given as a single dose to colorectal surgery patients. METHODS: A commercial
      database supplied demographics, All-Patient Refined Diagnosis-Related Groups (APR
      DRGs), International Classification of Disease (ICD)-9 codes, and drug
      utilization information for patients discharged from 303 hospitals from January
      2007-December 2008 whose charts had been sampled for reporting Surgical Care
      Improvement Project (SCIP) measures. The patients (n=4,634) had the same APR DRG,
      no baseline infection, and prophylaxis discontinued within 24 h of surgery.
      Development of infection was determined by ICD-9 code. "Single dose" was defined
      as <=3 g of ampicillin-sulbactam (AMP); <=2 g of cefotetan (CFT), cefoxitin
      (FOX), or ertapenem (ERT); or metronidazole and <=2 g of cefazolin (CFZ) or <=750
      mg of levofloxacin (LVX) given on the day of the procedure. Multivariable
      logistic regression evaluated factors associated with infection, including agent
      choice. RESULTS: Frequency of use and rate of infection (3.7% overall) were FOX
      1,752 (4.9%), ERT 1,166 (2.7%), CFZ 549 (2.7%), AMP 447 (3.6%), LVX 402 (3.2%),
      and CFT 318 (3.5%). The unadjusted infection rate differed by agent (p=0.037).
      Multiple regression analysis found infection to be associated significantly with
      increasing APR DRG severity, longer procedures, younger age, and male gender
      (p<0.01 for each except p=0.02 for age), as well as agent choice. Among agents
      (vs. FOX as reference), ERT was associated with a lower infection rate (odds
      ratio 0.53; 95% confidence interval 0.34-0.82; p<0.01); the odds ratio for all
      other agents contained the value 1.0. CONCLUSIONS: Agent selection among
      prophylactic antibiotics is one of many factors associated with infection
      development in colorectal surgery patients.

PMID- 22142317
TI  - Randomized trial of antimicrobial-coated sutures to prevent surgical site
      infection after breast cancer surgery.
AB  - BACKGROUND: Surgical site infection (SSI) is the fourth commonest healthcare
      associated infection and complicates at least 5% of open operations. In a
      randomized clinical trial, antimicrobial-coated sutures were compared with their
      conventional counterparts, polyglactin and poliglecaprone, for skin closure after
      breast cancer surgery to assess their role in reducing the rate of SSI. METHODS:
      Between November 2008 and February 2011, 150 female patients presenting with
      breast cancer to a single center were randomized to skin closure with
      antimicrobial-coated or plain sutures. Postoperatively, SSI was defined using the
      U.S. Centers for Disease Control and Prevention (CDC) definitions and scored
      using the ASEPSIS or Southampton systems by trained, blinded observers with close
      post-discharge surveillance and patient diaries. Surgeons and patients were
      blinded to the type of suture used. RESULTS: Using CDC criteria, the overall rate
      of SSI was 18.9% at six weeks. Six patients (4.7%) needed intervention or
      readmission for SSI. Skin closure with antimicrobial sutures showed a non
      statistically significant reduction in the SSI rate, to 15.2%, compared with
      conventional sutures (22.9%). A uniform tendency for fewer SSIs in the
      antimicrobial-coated suture group was found using ASEPSIS and Southampton scores,
      but again, the difference was not statistically significant. CONCLUSION: The
      previously reported high rate of SSI related to breast surgery was confirmed.
      Using statistical modeling and earlier reports, the study was powered to show a
      difference using ASEPSIS scores, but the modification used in this trial failed
      to find a difference. Finding a statistically significant difference would have
      needed two to three times the number of patients recruited. Further evaluation of
      antimicrobial-coated sutures is merited, particularly if used as part of a care
      bundle to reduce SSI after breast cancer surgery.

PMID- 22142318
TI  - Fifty ways to cause surgical site infections.

PMID- 22142319
TI  - Factors associated with post-operative conversion to methicillin-resistant
      Staphylococcus aureus positivity or infection in initially MRSA-negative
      patients.
AB  - BACKGROUND: Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA)
      is associated with morbid, invasive infections and has been implicated in nearly
      every type of nosocomial infection. Our aim was to identify the risk factors for
      patient conversion from MRSA negativity pre-operatively to MRSA positivity post
      operatively. METHODS: We retrospectively reviewed all patients at the Veterans
      Affairs-Boston Health Care System who underwent clean or clean-contaminated
      surgical procedures during the years 2008 and 2009 and had documented pre
      operative nasal polymerase chain reaction (PCR) testing for MRSA. We abstracted
      post-operative MRSA microbiologic testing results, MRSA infections, surgical site
      infections (SSIs), surgical prophylaxis data, and SSI risk index, as calculated
      using the Veterans Affairs Surgical Quality Improvement Project (VASQIP) database
      variables. All patients who had a negative nasal MRSA PCR result in the 31-day
      pre-operative period and did not have any positive MRSA clinical swab or culture
      in the 1-year pre-operative period were defined as MRSA-negative. These patients
      were classified as converters to MRSA positivity if they had at least one
      documented positive nasal MRSA PCR swab, culture, nosocomial infection, or SSI
      within 31 days post-operatively. RESULTS: Among 4,238 eligible patients, 3,890
      (92%) qualified as MRSA-negative pre-operatively. A total of 1,432 (37%) of these
      patients were assessed in the VASQIP database, of whom 34 (2%) converted to MRSA
      positivity post-operatively. On multivariable logistic regression analysis of the
      VASQIP sample, age (odds ratio [OR] 1.049; 95% confidence interval [CI] 1.016,
      1.083), SSI risk index (OR 2.863; 95% CI 1.251-6.554), and vancomycin prophylaxis
      alone or in combination (OR 3.223; 95% CI 1.174-8.845) were significantly
      associated with conversion to MRSA positivity. CONCLUSION: In pre-operatively
      MRSA-negative patients, age, SSI risk index, and vancomycin prophylaxis were
      significant factors for conversion to MRSA positivity post-operatively.
      Alternatives to vancomycin prophylaxis in non-colonized patients and optimization
      of patients' SSI risk factors should be considered before elective surgery.

PMID- 22142320
TI  - Multiple brain abscesses caused by Streptococcus pneumoniae: rare complication of
      lobar pneumonia.

PMID- 22142321
TI  - Simultaneous necrotizing soft tissue infection and colonic necrosis caused by
      Clostridium septicum.
AB  - BACKGROUND: Clostridial myonecrosis is an uncommon, highly lethal necrotizing
      soft tissue infection. The source may be occult at the time of clinical
      presentation. In cases caused by Clostridium septicum, there is an association
      with colorectal malignant disease, suggesting that underlying colonic pathology
      frequently is the source of the infection. METHODS: Case report and literature
      review. CASE REPORT: A 37-year old man with acquired immunodeficiency syndrome,
      end-stage renal disease, and C. difficile colitis presented to the Emergency
      Department (ED) with a primary complaint of abdominal pain and incidental right
      forearm pain. While undergoing evaluation in the ED, he developed progressive
      erythema, edema, and emergence of bullae over his right forearm. After rapid
      imaging of his abdomen, he underwent guillotine amputation of his right upper
      extremity because of extensive myonecrosis and total abdominal colectomy
      secondary to right colonic necrosis and C. difficile colitis. Blood cultures were
      positive for C. septicum. Microscopic examination of both the necrotic colon and
      the right forearm musculature demonstrated invasion of gram-positive bacilli
      throughout. CONCLUSIONS: Myonecrosis caused by C. septicum frequently occurs in
      the presence of colonic pathology, typically malignant disease. This case report
      illustrates the development of this pathological process in an immunosuppressed
      patient who did not have colon cancer, but rather colonic mucosal inflammation
      produced by C. difficile.

PMID- 22142322
TI  - Linking GPS and travel diary data using sequence alignment in a study of
      children's independent mobility.
AB  - BACKGROUND: Global positioning systems (GPS) are increasingly being used in
      health research to determine the location of study participants. Combining GPS
      data with data collected via travel/activity diaries allows researchers to assess
      where people travel in conjunction with data about trip purpose and
      accompaniment. However, linking GPS and diary data is problematic and to date the
      only method has been to match the two datasets manually, which is time consuming
      and unlikely to be practical for larger data sets. This paper assesses the
      feasibility of a new sequence alignment method of linking GPS and travel diary
      data in comparison with the manual matching method. METHODS: GPS and travel diary
      data obtained from a study of children's independent mobility were linked using
      sequence alignment algorithms to test the proof of concept. Travel diaries were
      assessed for quality by counting the number of errors and inconsistencies in each
      participant's set of diaries. The success of the sequence alignment method was
      compared for higher versus lower quality travel diaries, and for accompanied
      versus unaccompanied trips. Time taken and percentage of trips matched were
      compared for the sequence alignment method and the manual method. RESULTS: The
      sequence alignment method matched 61.9% of all trips. Higher quality travel
      diaries were associated with higher match rates in both the sequence alignment
      and manual matching methods. The sequence alignment method performed almost as
      well as the manual method and was an order of magnitude faster. However, the
      sequence alignment method was less successful at fully matching trips and at
      matching unaccompanied trips. CONCLUSIONS: Sequence alignment is a promising
      method of linking GPS and travel diary data in large population datasets,
      especially if limitations in the trip detection algorithm are addressed.

PMID- 22142323
TI  - A remarkable effect of alemtuzumab in a patient suffering from narcolepsy with
      cataplexy.

PMID- 22142324
TI  - "Recovery" in bipolar disorder: how can service users be supported through a self
      management intervention? A qualitative focus group study.
AB  - BACKGROUND: Bipolar disorder (BD) is a chronic and recurrent affective disorder.
      Recovery is defined as the process by which people can live fulfilling lives
      despite experiencing symptoms. AIMS: To explore how an opportunistically
      recruited group of service users with BD experience recovery and self-management
      to understand more about how a service users' recovery may be supported. METHOD:
      Twelve service users with BD took part in a series of focus groups. Service
      users' responses to questions about their personal experiences of self-management
      and recovery were analysed. Focus groups were transcribed verbatim and thematic
      analysis ([ Braun, V., & Clarke, V. (2006). Using thematic analysis in
      psychology. Qualitative Research in Psychology, 3(2), 77-101]) was employed to
      identify common themes in the data. RESULTS: Four key themes were identified: (1)
      Recovery is not about being symptom free; (2) Recovery requires taking
      responsibility for your own wellness; (3) Self-management: building on existing
      techniques; (4) Overcoming barriers to recovery: negativity, stigma and taboo.
      CONCLUSION: Service users with BD have provided further support for the concept
      of recovery and have suggested a number of ways recovery can be supported. A self
      management approach informed by the recovery literature has been proposed as a
      way to support service users' recovery.

PMID- 22142325
TI  - Absolute total electron impact ionization cross-sections for many-atom organic
      and halocarbon species.
AB  - The experimental determination of absolute total electron impact ionization cross
      sections for polyatomic molecules has traditionally been a difficult task and
      restricted to a small range of species. This article reviews the performance of
      three models to estimate the maximum ionization cross-sections of some 65
      polyatomic organic and halocarbon species. Cross-sections for all of the species
      studied have been measured experimentally using the same instrument, providing a
      complete data set for comparison with the model predictions. The three models
      studied are the empirical correlation between maximum ionization cross-section
      and molecular polarizability, the well-known binary encounter Bethe (BEB) model,
      and the functional group additivity model. The excellent agreement with
      experiment found for all three models, provided that calculated electronic
      structure parameters of suitably high quality are used for the first two, allows
      the prediction of total electron-impact ionization cross-sections to at least 7%
      precision for similar molecules that have not been experimentally characterized.

PMID- 22142326
TI  - Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with
      clinical, biochemical, and neuroradiological reversibility.
AB  - Pyruvate dehydrogenase complex (PDHC) deficiency causes encephalomyopathies, of
      which there are four major categories: (1) neonatal encephalopathy with lactic
      acidosis; (2) an early infantile form, which (3) at times resembles Leigh
      syndrome; and (4) a later-onset form. Long-term clinical and radiological follow
      up is still incompletely elucidated. We report a 12-year-old male with
      intermittent-relapsing PDHC deficiency who presented with three typical acute
      episodes of metabolic decompensation over 7 years. Neuroimaging showed reversible
      signal abnormalities in the basal ganglia, inferior olivary nuclei,
      periaqueductal grey matter, and dentate nuclei, with evidence of lactate on
      magnetic resonance spectroscopy. Molecular analysis of PDH1A revealed a novel
      hemizygous c.1045G>A mutation, predicting a p.A349T missense mutation. He was
      treated with thiamine supplementation and, while on this regimen, he experienced
      several intercurrent febrile episodes without neurological compromise. This case
      report stresses the importance of performing neuroimaging during acute clinical
      episodes because brain lesions in PDHC deficiency may be transient and
      reversible, and false-negative results may mislead the diagnosis and delay the
      treatment.

PMID- 22142328
TI  - Coexistence of Bowenoid papulosis and Bowen's disease in a patient with systemic
      lupus erythematosus.

PMID- 22142329
TI  - Construction of sensitive and selective zirconia-based CO sensors using ZnCr2O(4)
      based sensing electrodes.
AB  - The carbon monoxide (CO) sensitivity of a mixed-potential-type yttria-stabilized
      zirconia (YSZ)-based tubular-type sensor utilizing a ZnCr(2)O(4) sensing
      electrode (SE) was tuned by the addition of different precious metal
      nanoparticles (Ag, Au, Ir, Pd, Pt, Ru and Rh; 1 wt % each) into the sensing
      layer. After measuring the electromotive force (emf) response of the fabricated
      SEs to 100 ppm of CO against a Pt/air-reference electrode (RE), the ZnCr(2)O(4)
      Au nanoparticle composite electrode (ZnCr(2)O(4)(+Au)-SE) was found to give the
      highest response to CO. A linear dependence on the logarithm of CO concentration
      in the range of 20-800 ppm at an operational temperature of 550  degrees C under
      humid conditions (5 vol % water vapor) was observed. From the characterization of
      the ZnCr(2)O(4)(+Au)-SE, we can conclude that the engineered high response toward
      CO originated from the specific properties of submicrometer sized Au particles,
      formed via the coalescence of nanosized Au particles located on ZnCr(2)O(4)
      grains, during the calcining process at 1100  degrees C for 2 h. These particles
      augmented the catalytic activities of the gas-phase CO oxidation reaction in the
      SE layer, as well as to the anodic reaction of CO at the interface; while
      suppressing the cathodic reaction of O(2) at the interface. In addition, the
      response of the ZnCr(2)O(4)(+Au)-SE sensor toward 100 ppm of CO gradually
      increased throughout the 10 days of operation, and plateaued for the remainder of
      the month that the sensor was examined. Correlations between SEM observations and
      the CO sensing characteristics of the present sensor were suggestive that the
      sensitivity was mostly affected by the morphology of the Au particles and their
      catalytic activities, which were in close proximity to the ZnCr(2)O(4) grains.
      Furthermore, by measuring the potential difference (emf) between the
      ZnCr(2)O(4)(+Au) and a ZnCr(2)O(4) electrode, sensitivities to typical exhaust
      component gases other than CO were found to be negligible at 550  degrees C.

PMID- 22142327
TI  - Rationale, design, and implementation protocol of the Dutch clinical practice
      guideline pain in patients with cancer: a cluster randomised controlled trial
      with Short Message Service (SMS) and Interactive Voice Response (IVR).
AB  - BACKGROUND: One-half of patients with cancer have pain. In nearly one out of two
      cancer patients with pain, this was undertreated. Inadequate pain control still
      remains an important problem in this group of patients. Therefore, in 2008 a
      national, evidence-based multidisciplinary clinical practice guideline 'pain in
      patients with cancer' has been developed. Yet, publishing a guideline is not
      enough. Implementation is needed to improve pain management. An innovative
      implementation strategy, Short Message Service with Interactive Voice Response
      (SVS-IVR), has been developed and pilot tested. This study aims to evaluate on
      effectiveness of this strategy to improve pain reporting, pain measurement and
      adequate pain therapy. In addition, whether the active role of the patient and
      involvement of caregivers in pain management may change. METHODS/DESIGN: A
      cluster randomised controlled trial with two arms will be performed in six
      oncology outpatient clinics of hospitals in the Southeastern region of the
      Netherlands, with three hospitals in the intervention and three in the control
      condition. Follow-up measurements will be conducted in all hospitals to study the
      long-term effect of the intervention. The intervention includes training of
      professionals (medical oncologists, nurses, and general practitioners) and SMS
      IVR to report pain in patients with cancer to improve pain reporting by patients,
      pain management by medical oncologists, nurses, and general practitioners, and
      decrease pain intensity. DISCUSSION: This innovative implementation strategy with
      technical tools and the involvement of patients, may enhance the use of the
      guideline 'pain in patients with cancer' for pain management. Short Message
      Service alerts may serve as a tool to support self-management of patients.
      Therefore, the SMS-IVR intervention may increase the feeling of having control
      over one's life. TRIAL REGISTRATION: [corrected] Netherlands Trial Register
      (NTR): NTR2739.

PMID- 22142330
TI  - DMXAA (Vadimezan, ASA404) is a multi-kinase inhibitor targeting VEGFR2 in
      particular.
AB  - The flavone acetic acid derivative DMXAA [5,6-dimethylXAA (xanthenone-4-acetic
      acid), Vadimezan, ASA404] is a drug that displayed vascular-disrupting activity
      and induced haemorrhagic necrosis and tumour regression in pre-clinical animal
      models. Both immune-mediated and non-immune-mediated effects contributed to the
      tumour regression. The vascular disruption was less in human tumours, with immune
      mediated effects being less prominent, but nonetheless DMXAA showed promising
      effects in Phase II clinical trials in non-small-cell lung cancer. However, these
      effects were not replicated in Phase III clinical trials. It has been difficult
      to understand the differences between the pre-clinical findings and the later
      clinical trials as the molecular targets for the agent have never been clearly
      established. To investigate the mechanism of action, we sought to determine
      whether DMXAA might target protein kinases. We found that, at concentrations
      achieved in blood during clinical trials, DMXAA has inhibitory effects against
      several kinases, with most potent effects being on members of the VEGFR (vascular
      endothelial growth factor receptor) tyrosine kinase family. Some analogues of
      DMXAA were even more effective inhibitors of these kinases, in particular 2-MeXAA
      (2-methylXAA) and 6-MeXAA (6-methylXAA). The inhibitory effects were greatest
      against VEGFR2 and, consistent with this, we found that DMXAA, 2-MeXAA and 6
      MeXAA were able to block angiogenesis in zebrafish embryos and also inhibit
      VEGFR2 signalling in HUVECs (human umbilical vein endothelial cells). Taken
      together, these results indicate that at least part of the effects of DMXAA are
      due to it acting as a multi-kinase inhibitor and that the anti-VEGFR activity in
      particular may contribute to the non-immune-mediated effects of DMXAA on the
      vasculature.

PMID- 22142331
TI  - Intra- and postoperative adverse events in children with nephrotic syndrome
      requiring surgery under general anesthesia.
AB  - BACKGROUND: There are few data regarding perioperative adverse events in children
      with nephrotic syndrome. OBJECTIVES: The aim of this study was to describe the
      nature and frequency of perioperative adverse events in children with nephrotic
      syndrome. MATERIALS AND METHODS: This is a retrospective study from a large
      university pediatric hospital. All procedures under general anesthesia in
      children with nephrotic syndrome between January 1995 and May 2007 were included,
      with the exception of renal transplantation. Data were collected on demographics,
      etiology of nephrotic syndrome and related treatments, surgical procedures and
      anesthetic techniques, and pre- and postoperative treatments. Adverse events
      occurring during the intraoperative period and up to the fifth postoperative day
      were recorded. RESULTS: Data on eight patients who underwent 24 surgical or
      interventional procedures under general anesthesia over the study period were
      reviewed. Three patients had steroid-resistant nephrotic syndrome and five
      patients had congenital or infantile nephrotic syndrome. Five patients had
      progressed to end-stage renal failure requiring dialysis. General anesthesia was
      performed for: nephrectomy (n = 9), central venous catheter insertion (n = 8),
      peritoneal dialysis catheter insertion (n = 5), and emergency surgery in two
      cases (acute intestinal intussusception and hemodialysis catheter insertion).
      Three patients were receiving aspirin and one anticoagulant therapy. No
      postoperative thrombosis or infections, bleeding, peripheral edema or ascites,
      and increase in kalemia were noted. There was no significant postoperative
      increase in median serum creatinine level. CONCLUSIONS: Surgical procedures were
      seldom associated with the occurrence of perioperative adverse events. However,
      larger studies are needed to confirm these results.

PMID- 22142334
TI  - Uptake of fluoride from aqueous solution on nano-sized hydroxyapatite:
      examination of a fluoridated surface layer.
AB  - Hydroxyapatite (Ca(10)(PO(4))(6)(OH)(2), HAP), both as a synthetic material and
      as a constituent of bone char, can serve as an effective and relatively
      inexpensive filter material for fluoride (F(-)) removal from drinking water in
      low-income countries. Fluoride uptake on HAP can occur through different
      mechanisms, which are, in principle, influenced by solution composition.
      Suspensions of HAP (2 g L(-1)) were equilibrated under controlled pH conditions
      (pH 6.5, 7.3, 9.5) at 25  degrees C for 28 d after the addition of different F(-)
      concentrations (0.5-7.0 mM). The reacted HAP solids were examined with
      Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy
      (FTIR), X-ray Photoelectron Spectroscopy (XPS), and Nano Secondary Ion Mass
      Spectroscopy (NanoSIMS). Fluoride uptake on HAP was dependent on pH, with the
      highest capacity at pH 6.5; the lowest uptake was found at pH 9.5. Under all
      experimental conditions, the thermodynamically stable mineral phase was
      fluorapatite, (Ca(10)(PO(4))(6)F(2), FAP). Fluoride uptake capacity was
      quantified on the basis of FTIR and XPS analysis, which was consistent with F(-)
      uptake from solution. The results of XPS and NanoSIMS analyses indicate that a
      fluoridated surface layer with a thickness of several nanometers is formed on
      nanosized HAP.

PMID- 22142332
TI  - Effect of pegylated interferon-alpha-2a treatment on mental health during recent
      hepatitis C virus infection.
AB  - BACKGROUND AND AIM: Pegylated interferon (PEG-IFN) treatment for hepatitis C
      virus (HCV) infection has neuropsychiatric side effects. Data on the effect of
      HCV treatment on mental health among injecting drug users (IDUs) are limited. We
      assessed mental health during treatment of recently acquired HCV, within a
      predominantly IDU population. METHODS: Participants with HCV received PEG-IFN
      alpha-2a (180 ug/week) for 24 weeks; HCV/HIV received PEG-IFN with ribavirin.
      Depression was assessed using the Mini-International Neuropsychiatric Interview
      (MINI). Logistic regression was used to identify factors associated with
      depression at enrolment and during treatment. Also, the effect of depression
      prior to and during treatment on sustained virological response (SVR) was
      assessed. RESULTS: Of 163 participants, 111 received treatment (HCV, n = 74;
      HCV/HIV, n = 37), with 76% ever reporting IDU. At enrolment, 16% had depression
      (n = 25). In adjusted analysis, depression at enrolment occurred less often in
      participants full-/part-time employed (adjusted odds ratio [AOR] 0.23; 95%
      confidence interval [CI]: 0.06, 0.82, P = 0.023) and more often in recent IDUs
      (AOR 3.04; 95% CI: 1.19, 7.72, P = 0.019). During treatment, 35% (n = 31)
      developed new-onset depression. In adjusted analysis, poorer social functioning
      (higher score) was associated with new-onset depression (score <= 9 vs score >=
      17; OR 5.69; 95% CI: 1.61, 20.14, P = 0.007). SVR was similar among participants
      with and without depression at enrolment (60% vs 61%, P = 0.951) and in those
      with and without new-onset depression (74% vs 63%, P = 0.293). CONCLUSIONS:
      Although depression at enrolment and during treatment was common among
      participants with recent HCV, neither influenced SVR. Participants with poor
      social functioning may be most at risk of developing depression during HCV
      therapy.

PMID- 22142333
TI  - Meta-analysis of 8q24 for seven cancers reveals a locus between NOV and ENPP2
      associated with cancer development.
AB  - BACKGROUND: Human chromosomal region 8q24 contains several genes which could be
      functionally related to cancer, including the proto-oncogene c-MYC. However, the
      abundance of associations around 128 Mb on chromosome 8 could mask the appearance
      of a weaker, but important, association elsewhere on 8q24. METHODS: In this
      study, we completed a meta-analysis of results from nine genome-wide association
      studies for seven types of solid-tumor cancers (breast, prostate, pancreatic,
      lung, ovarian, colon, and glioma) to identify additional associations that were
      not apparent in any individual study. RESULTS: Fifteen SNPs in the 8q24 region
      had meta-analysis p-values < 1E-04. In particular, the region consisting of
      120,576,000-120,627,000 bp contained 7 SNPs with p-values < 1.0E-4, including
      rs6993464 (p = 1.25E-07). This association lies in the region between two genes,
      NOV and ENPP2, which have been shown to play a role in tumor development and
      motility. An additional region consisting of 5 markers from 128,478,000 bp -
      128,524,000 (around gene POU5F1B) had p-values < 1E-04, including rs6983267,
      which had the smallest p-value (p = 6.34E-08). This result replicates previous
      reports of association between rs6983267 and prostate and colon cancer.
      CONCLUSIONS: Further research in this area is warranted as these results
      demonstrate that the chromosomal region 8q24 may contain a locus that influences
      general cancer susceptibility between 120,576 and 120,630 kb.

PMID- 22142335
TI  - Retrograde intrarenal surgery in treatment of nephrolithiasis: is a 100% stone
      free rate achievable?
AB  - PURPOSE: To achieve an almost 100% stone-free rate by means of further developing
      and standardizing the procedure. PATIENTS AND METHODS: 100 consecutive patients
      with single or multiple renal calculi were prospectively enrolled in the study.
      Flexible ureterorenoscopy was performed as a completely standardized operation by
      the same two experienced surgeons. Primary outcome was an "endoscopic"
      (immediate) stone-free status as determined by endoscopic inspection at the end
      of surgery. In cases of residual fragments, a reevaluation by CT was performed
      after 3 months. RESULTS: The endoscopic stone-free rate was 97%. In three
      patients with a cumulative stone size >20 mm, a completely stone-free status
      could not be achieved in the primary procedure. In these patients, a CT scan
      after 3 months showed complete clearance from all residual fragments in two; this
      translates into a primary (after one procedure) stone-free rate after 3 months of
      99%. Medium cumulative stone size was 9.8 mm (4-40 mm); in 44 patients, multiple
      calculi were extracted. Forty-nine patients received a ureteral stent at the end
      of the operation; two patients had to have stent placement for new onset
      hydronephrosis and/or colicky pain or fever. Overall complication rate was 7%.
      Results are limited, because no routine CT scan was used to evaluate stone
      clearance. CONCLUSION: By means of a standardized surgical approach and use of
      technical equipment of the newest generation, it is possible to achieve very high
      stone-free rates without compromising safety. This approach, however,
      necessitates use of considerable resources, both technical/surgical and
      financial.

PMID- 22142336
TI  - Proteomic analysis of the secretions of Pseudallescheria boydii, a human fungal
      pathogen with unknown genome.
AB  - Pseudallescheria boydii is a filamentous fungus that causes a wide array of
      infections that can affect practically all the organs of the human body. The
      treatment of pseudallescheriosis is difficult since P. boydii exhibits intrinsic
      resistance to the majority of antifungal drugs used in the clinic and the
      virulence attributes expressed by this fungus are unknown. The study of the
      secretion of molecules is an important approach for understanding the
      pathogenicity of fungi. With this task in mind, we have shown that mycelial cells
      of P. boydii were able to actively secrete proteins into the extracellular
      environment; some of them were recognized by antibodies present in the serum of a
      patient with pseudallescheriosis. Additionally, molecules secreted by P. boydii
      induced in vitro irreversible damage in pulmonary epithelial cells. Subsequently,
      two-dimensional gel electrophoresis combined with mass spectrometry was carried
      out in order to start the construction of a map of secreted proteins from P.
      boydii mycelial cells. The two-dimensional map showed that most of the proteins
      (around 100 spots) were focused at pH ranging from 4 to 7 with molecular masses
      ranging from 14 to >117 kDa. Fifty spots were randomly selected, of which 30
      (60%) were consistently identified, while 20 (40%) spots generated peptides that
      showed no resemblance to any known protein from other fungi and/or MS with low
      quality. Notably, we identified proteins involved in metabolic pathways
      (energy/carbohydrate, nucleotide, and fatty acid), cell wall remodeling, RNA
      processing, signaling, protein degradation/nutrition, translation machinery, drug
      elimination and/or detoxification, protection against environmental stress,
      cytoskeleton/movement proteins, and immunogenic molecules. Since the genome of
      this fungus is not sequenced, we performed enzymatic and immunodetection assays
      in order to corroborate the presence of some released proteins. The
      identification of proteins actively secreted by P. boydii provides important new
      information for understanding immune modulation and provides important new
      perspectives on the biology of this intriguing fungus.

PMID- 22142337
TI  - Control of substrate specificity by a single active site residue of the KsgA
      methyltransferase.
AB  - The KsgA methyltransferase is universally conserved and plays a key role in
      regulating ribosome biogenesis. KsgA has a complex reaction mechanism,
      transferring a total of four methyl groups onto two separate adenosine residues,
      A1518 and A1519, in the small subunit rRNA. This means that the active site
      pocket must accept both adenosine and N(6)-methyladenosine as substrates to
      catalyze formation of the final product N(6),N(6)-dimethyladenosine. KsgA is
      related to DNA adenosine methyltransferases, which transfer only a single methyl
      group to their target adenosine residue. We demonstrate that part of the
      discrimination between mono- and dimethyltransferase activity lies in a single
      residue in the active site, L114; this residue is part of a conserved motif,
      known as motif IV, which is common to a large group of S-adenosyl-L-methionine
      dependent methyltransferases. Mutation of the leucine to a proline mimics the
      sequence found in DNA methyltransferases. The L114P mutant of KsgA shows
      diminished overall activity, and its ability to methylate the N(6)
      methyladenosine intermediate to produce N(6),N(6)-dimethyladenosine is impaired;
      this is in contrast to a second active site mutation, N113A, which diminishes
      activity to a level comparable to L114P without affecting the methylation of N(6)
      methyladenosine. We discuss the implications of this work for understanding the
      mechanism of KsgA's multiple catalytic steps.

PMID- 22142338
TI  - Gap junctions mediate STAT5-independent beta-casein expression in CID-9 mammary
      epithelial cells.
AB  - Crosstalk between gap junction intracellular communication (GJIC), STAT5 and OCT
      1 in gap junction (GJ)-dependent beta-casein expression was investigated. CID-9
      mammary cells plated with prolactin on non-adherent substratum (poly-HEMA)
      expressed beta-casein independent of STAT5 only in the presence of the GJIC
      inducer, cAMP. Nuclear STAT5 levels were not detectable. By contrast, cells on
      EHS-drip expressed beta-casein in a STAT5-dependent manner and nuclear STAT5
      levels were up-regulated. A 75 kDa OCT-1 isoform was detected in conditions that
      induced beta-casein expression regardless of substratum. Interestingly, 40 and 28
      kDa OCT-1 isoforms were induced in cells on polyHEMA with cAMP. Electrophoretic
      mobility shift assays (EMSA) for OCT-1 revealed two band shifts in cells on
      polyHEMA with cAMP and on EHS-drip, which were repressed by the GJIC inhibitor,
      18alpha-GA. These studies demonstrated that mammary cells on polyHEMA expressed
      beta-casein in response to prolactin in a pathway that involves GJIC and OCT-1
      and is independent of STAT5 nuclear translocation.

PMID- 22142340
TI  - Ordered microporous membranes templated by breath figures for size-selective
      separation.
AB  - Membranes with highly uniform pore size are important in various fields. Here we
      report the preparation and performance of ordered membranes, the pore diameter of
      which is on the micrometer scale. The ordered membranes fabricated at two-phase
      interfaces enable a high-resolution and energy-saving separation process.
      Moreover, a possible mechanism for the formation of through-pores has been
      proposed and experimentally verified.

PMID- 22142342
TI  - Traumatic brain injury during warfarin anticoagulation: an experimental study in
      mice.
AB  - The number of patients who are on long-term anticoagulation therapy while
      experiencing traumatic brain injury (TBI) is rising. This experimental study
      evaluated whether warfarin pre-treatment increases brain hemorrhage and worsens
      functional outcome after TBI, and whether the rapid reversal of anticoagulation
      after TBI prevents warfarin-exacerbated brain damage. Normal CD-1 mice (C) and
      mice pre-treated with warfarin (W) to an International Normalized Ratio of 3.5+/
      0.9 underwent TBI using a controlled cortical impact model. Mean hemorrhage
      volume 24 h after TBI was 1.2+/-0.4 MUL in C mice and 10.9+/-6.9 MUL in W mice
      (p=0.029, n=4 per group). In a second study, anticoagulated mice received either
      saline (W-S) or prothrombin complex concentrate (W-PCC, 100 U/kg) intravenously
      60 min after TBI. Anticoagulation reversal using PCC (W-PCC mice) reduced
      hemorrhage volumes as compared to W-S animals (7.3+/-6.0 versus 19.8+/-14.0 MUL,
      p=0.045, n=8 per group). In a third study, we examined motor deficits and lesion
      volume in C, W-S, and W-PCC mice until 33 days after injury. Functional outcome
      and lesion volume were no different between groups (n=10 per group). In
      conclusion, we characterized an experimental model of TBI occurring during
      warfarin anticoagulation. Anticoagulation led to higher intracerebral blood
      volumes, but did not significantly worsen functional outcome. The rapid reversal
      of anticoagulation may be effective in preventing excess bleeding.

PMID- 22142341
TI  - Comparative effect of pre-coseasonal and continuous grass sublingual
      immunotherapy in children.
AB  - BACKGROUND: One of the most important aspects of sublingual immunotherapy (SLIT)
      is the regimen of administration. The aim of the study was to compare the
      efficacy and the safety of SLIT given pre-coseasonally (starting before the
      pollen season and continuing until the end of it) and continuously (all year
      round, independent of the pollen season) in children allergic to grass pollen.
      METHODS: Sixty children aged 6-18, sensitive only to grass pollen, with rhinitis
      (20 patients had concomitant asthma) participated in the 2-year prospective,
      randomized, double-blind, placebo-controlled trial. RESULTS: Both pre-coseasonal
      and continuous SLIT were associated with a substantial reduction in the combined
      symptoms/medication score when compared with placebo; there were no significant
      differences between the regimens (mean difference: 18.1 +/- 12.4, P > 0.05).
      Similar changes were observed in the total symptoms score. Pre-coseasonal
      therapy, compared with continuous, was more effective in the reduction of nasal
      symptoms (mean difference: -18.0 +/- 2.5, P = 0.006). We did not observe
      significant differences in medication, ocular, and asthma scores between the
      regimens. We did not observe changes in morning PEF, FEV1, and PD20 in any of the
      three groups nor between the groups throughout the study. We showed a significant
      decrease in FeNO level comparable in both active groups. There were no
      differences between groups in the induction of CD4CD25Foxp3-positive cells in
      peripheral blood during the study. CONCLUSION: Both protocols were effective
      compared with placebo and showed similar decreases for combined
      symptoms/medication score and all secondary endpoints, with the exception of
      nasal symptoms that were lower in the pre-coseasonal group.

PMID- 22142339
TI  - Using the reconstructed genome-scale human metabolic network to study physiology
      and pathology.
AB  - Metabolism plays a key role in many major human diseases. Generation of high
      throughput omics data has ushered in a new era of systems biology. Genome-scale
      metabolic network reconstructions provide a platform to interpret omics data in a
      biochemically meaningful manner. The release of the global human metabolic
      network, Recon 1, in 2007 has enabled new systems biology approaches to study
      human physiology, pathology and pharmacology. There are currently more than 20
      publications that utilize Recon 1, including studies of cancer, diabetes, host
      pathogen interactions, heritable metabolic disorders and off-target drug binding
      effects. In this mini-review, we focus on the reconstruction of the global human
      metabolic network and four classes of its application. We show that computational
      simulations for numerous pathologies have yielded clinically relevant results,
      many corroborated by existing or newly generated experimental data.

PMID- 22142343
TI  - Why are we still using hydrochlorothiazide?

PMID- 22142344
TI  - The genetics of hypertension--where to look?

PMID- 22142345
TI  - UK guidelines call for routine 24-hour ambulatory blood pressure monitoring in
      all patients to make the diagnosis of hypertension--not ready for prime time in
      the United States.

PMID- 22142346
TI  - 24-hour efficacy and safety of Triple-Combination Therapy With Olmesartan,
      Amlodipine, and Hydrochlorothiazide: the TRINITY ambulatory blood pressure
      substudy.
AB  - This 12-week, multicenter, randomized, double-blinded, 4-arm study in 440
      patients with moderate to severe hypertension compared ambulatory blood pressure
      (ABP) responses with a triple-combination regimen (olmesartan medoxomil [OM] 40
      mg, amlodipine besylate [AML] 10 mg, and hydrochlorothiazide [HCTZ] 25 mg) and
      its component dual-combination regimens at similar doses. At week 12, the triple
      combination resulted in a greater reduction in mean 24-hour systolic and
      diastolic blood pressure (-30.3/-18.0 mm Hg) compared with the 3 dual-combination
      regimens (OM 40 mg/AML 10 mg: -23.5/-13.9, OM 40 mg/HCTZ 25 mg: -23.9/-14.5, and
      AML 10 mg/HCTZ 25 mg: -18.5 mm Hg/-10.7 mm Hg; P<.0001 each). Greater efficacy
      was also found during daytime and nighttime hours and during the last 6, 4, or 2
      hours of the dosing interval. The authors conclude that the triple combination of
      OM 40 mg/AML 10 mg/HCTZ 25 mg demonstrated superior efficacy and sustained
      reductions in ABP compared with its dual-combination components.

PMID- 22142347
TI  - Can personal exposures to higher nighttime and early-morning temperatures
      increase blood pressure?
AB  - Environmental temperatures are inversely related to BP; however, the effects of
      short-term temperature changes within a 24-hour period and measured with high
      accuracy at the personal level have not been described. Fifty-one nonsmoking
      patients living in the Detroit area had up to 5 consecutive days of 24-hour
      personal-level environmental temperature (PET) monitoring along with daily
      cardiovascular measurements, including BP, performed mostly between 5 pm and 7 pm
      during summer and/or winter periods. The associations between hour-long mean PET
      levels during the previous 24 hours with the outcomes were assessed by linear
      mixed models. Accounting for demographics, environmental factors, and monitoring
      compliance, systolic and diastolic BP were positively associated with several
      hour-long PET measurements ending from 10 to 15 hours beforehand. During this
      time, corresponding mostly to a period starting from between 1 am and 3 am to
      ending between 7 am and 9 am, an increase of 1 degrees C was associated with a
      0.81 mm Hg to 1.44 mm Hg and 0.59 mm Hg to 0.83 mm Hg elevation in systolic and
      diastolic BP, respectively. Modestly warmer, commonly encountered PET levels
      posed a clinically meaningful effect (eg, a 6.95 mm Hg systolic pressure increase
      per interquartile range (4.8 degrees C) elevation at lag hour 10). Community
      level outdoor ambient temperatures were not related to BP. The authors provide
      the first evidence that personal exposure to warmer nighttime and early-morning
      environmental temperatures might lead to an increase in BP during the ensuing
      day.

PMID- 22142348
TI  - Comparison of aliskiren/hydrochlorothiazide combination therapy and amlodipine
      monotherapy in patients with stage 2 systolic hypertension and type 2 diabetes
      mellitus.
AB  - Patients with stage 2 hypertension and diabetes are at high cardiovascular risk
      and require large blood pressure (BP) reductions to reach treatment goals. This
      randomized double-blind study compared aliskiren/hydrochlorothiazide (HCTZ)
      combination therapy with amlodipine monotherapy in 860 patients with mean sitting
      systolic BP (msSBP) >=160 mm Hg to <200 mm Hg and type 2 diabetes. Patients
      received either once-daily aliskiren/HCTZ 150/12.5 mg or amlodipine 5 mg for 1
      week then force-titrated to double the doses for 7 weeks. Baseline BP was
      167.7/91.4 mm Hg. At week 8 end point, aliskiren/HCTZ provided significantly
      greater reductions in msSBP than amlodipine (28.8 mm Hg vs 26.2 mm Hg; P<.05).
      Mean sitting diastolic BP reductions were similar with aliskiren/HCTZ (9.9 mm Hg)
      and amlodipine (9.0 mm Hg). Achievement of BP control (<130/80 mm Hg) was
      significantly greater with aliskiren/HCTZ (23.2%) than amlodipine (13.8%;
      P<.0001). Aliskiren/HCTZ provides substantial msSBP reductions and greater BP
      control rates than amlodipine, and offers an attractive treatment option for
      patients with hypertension and diabetes mellitus.

PMID- 22142349
TI  - Single-pill vs free-equivalent combination therapies for hypertension: a meta
      analysis of health care costs and adherence.
AB  - This meta-analysis compares health care resource use costs, adherence, and
      persistence between groups of patients taking antihypertensives as single-pill
      combinations (SPCs) vs free-equivalent components (FEC) based on a structured
      review of published studies. The search yielded 12 retrospective database studies
      included in analyses. The mean difference in combined total annual all-cause and
      hypertension-related health care costs was $1357 (95% confidence interval [CI],
      $778-$1935) lower in favor of SPC than FEC groups. Adherence, measured as the
      mean difference in medication possession ratio, was estimated to be 8% higher for
      patients naive to prior antihypertensives and 14% higher for nonnaive SPC
      patients compared with corresponding FEC patients. Persistence in the SPC groups
      was twice as likely as the FEC groups (pooled risk ratio, 2.1; 95% CI, 1.1-4.1).
      Improved adherence and persistence may have contributed to the lower costs in the
      SPC groups via improved clinical outcomes.

PMID- 22142350
TI  - Evaluation of the migraine treatment sumatriptan/naproxen sodium on blood
      pressure following long-term administration.
AB  - Anti-inflammatory and pain therapies have been associated with blood pressure
      (BP) destabilization. Hence, the effects on BP of sumatriptan/naproxen sodium in
      fixed-dose combination, sumatriptan 85 mg, and naproxen sodium 500 mg
      administered intermittently for the acute treatment of migraine attacks were
      assessed. Patients with migraine with or without aura and no history of
      hypertension were randomized to sumatriptan/naproxen sodium (n=135), sumatriptan
      (n=136), or naproxen sodium (n=136) to treat migraine attacks for 6 months in a
      double-blind, parallel-group trial. Following a treated migraine attack, patients
      performed 2 consecutive days of self-measured BPs beginning >=24 hours after the
      last dose of study medication and transmitted them by a transtelephonic modem.
      The primary end point was the change from baseline in self-measured BP at 6
      months. Changes in self-measured BP from baseline to 6 months for
      sumatriptan/naproxen sodium were -2.1/-1.5 mm Hg (95% confidence intervals, -3.4
      to -0.8 for systolic and -2.6 to -0.3 for diastolic). Mean changes from baseline
      in self-measured BP did not differ among the 3 treatment groups. Additional
      categorical analyses did not show increases from baseline with
      sumatriptan/naproxen sodium relative to either of the monotherapy groups.
      Intermittent acute migraine treatment with sumatriptan/naproxen sodium for up to
      6 months was associated with clinically insignificant decreases in self-measured
      BP that were similar to those with sumatriptan or naproxen alone in normotensive
      patients with migraine.

PMID- 22142351
TI  - Carvedilol reduces aortic wave reflection and improves left ventricular/vascular
      coupling: a comparison with atenolol (CENTRAL Study).
AB  - Blood pressure (BP) characteristics, such as central aortic pressure and arterial
      stiffness, independently predict cardiovascular events. The effects of
      pharmacologically dissimilar beta-blockers on these properties have not been
      fully elucidated. Patients with essential hypertension and without significant
      concomitant cardiovascular disease were randomly assigned to controlled-release
      carvedilol, force-titrated to 80 mg (n=22), or atenolol, force-titrated to 100 mg
      (n=19); each was given once daily for 4 weeks. Baseline characteristics were
      similar. At the end of week 4, atenolol and carvedilol reduced central and
      brachial systolic and diastolic BP to a similar extent. Central augmentation
      index was increased in atenolol-treated patients but not carvedilol-treated
      patients (atenolol 4.47% vs carvedilol -0.68%; P=.04). Mean augmented central
      aortic pressure increased slightly during atenolol treatment (+1.1 mm Hg) but
      decreased slightly during carvedilol treatment (-1.1 mm Hg), although the
      difference in these changes was not statistically significant (P=.23). Pulse
      pressure amplification was reduced more with atenolol at week 4 (atenolol -10.7%
      vs carvedilol -1.8%; P=.02). Therefore, we conclude that carvedilol results in
      more favorable pulse pressure amplification and augmentation index by increasing
      arterial compliance and reducing the magnitude of wave reflection, respectively,
      compared with atenolol.

PMID- 22142352
TI  - Relationship between body mass index and high cystatin levels among US adults.
AB  - High cystatin C levels among patients without clinically recognized chronic
      kidney disease (CKD) may identify patients who are at preclinical stages of CKD.
      Higher body mass index (BMI) has been found to be associated with increased risk
      of CKD. However, the association between BMI and high cystatin C levels is not
      clear. The authors examined participants older than 20 years from the National
      Health and Nutrition Examination Survey 1999 to 2002 (N=2583, 50.2% women). BMI
      was categorized as <25 kg/m(2), 25-29.9 kg/m(2), and >=30 kg/m(2) . Main outcome
      was high cystatin C (>1 mg/dL) among patients without clinically recognized CKD
      (estimated glomerular filtration rate <60 mL/min/1.73 m(2) or microalbuminuria).
      Higher BMI was positively associated with high cystatin C, independent of age,
      sex, race-ethnicity, education, smoking, alcohol intake, cholesterol, and C
      reactive protein levels. Compared with patients with BMI <25 kg/m(2) (referent),
      the multivariable odds ratio (95% confidence interval) of high cystatin C was
      2.53 (1.79-3.58) (P trend <.0001 among patients with BMI >=30 kg/m(2)). The
      association between BMI and high cystatin C persisted in subgroup analyses by
      sex, race-ethnicity, and among those without diabetes or hypertension. Among US
      adults without clinically recognized CKD, higher BMI levels were independently
      associated with high cystatin C levels.

PMID- 22142353
TI  - Renal denervation revisited: promising treatment for resistant hypertension?

PMID- 22142354
TI  - Attention of salt awareness to prevent hypertension in the young.

PMID- 22142355
TI  - Sea salt (for Wendy).

PMID- 22142357
TI  - Inhibitory potential of omega-3 fatty and fenugreek essential oil on key enzymes
      of carbohydrate-digestion and hypertension in diabetes rats.
AB  - BACKGROUND: diabetes is a serious health problem and a source of risk for
      numerous severe complications such as obesity and hypertension. Treatment of
      diabetes and its related diseases can be achieved by inhibiting key digestives
      enzymes-related to starch digestion secreted by pancreas. METHODS: The
      formulation omega-3 with fenugreek terpenenes was administrated to surviving
      diabetic rats. The inhibitory effects of this oil on rat pancreas alpha-amylase
      and maltase and plasma angiotensin-converting enzyme (ACE) were determined.
      RESULTS: the findings revealed that administration of formulation omega-3 with
      fenugreek terpenenes (Om3/terp) considerably inhibited key enzymes-related to
      diabetes such as alpha-amylase activity by 46 and 52% and maltase activity by 37
      and 35% respectively in pancreas and plasma. Moreover, the findings revealed that
      this supplement helped protect the beta-Cells of the rats from death and damage.
      Interestingly, the formulation Om3/terp modulated key enzyme related to
      hypertension such as ACE by 37% in plasma and kidney. Moreover administration of
      fenugreek essential oil to surviving diabetic rats improved starch and glucose
      oral tolerance additively. Furthermore, the Om3/terp also decreased significantly
      the glucose, triglyceride (TG) and total-cholesterol (TC) and LDL-cholesterol
      (LDL-C) rates in the plasma and liver of diabetic rats and increased the HDL
      Cholesterol (HDL-Ch) level, which helped maintain the homeostasis of blood lipid.
      CONCLUSION: overall, the findings of the current study indicate that this
      formulation Om3/terp exhibit attractive properties and can, therefore, be
      considered for future application in the development of anti-diabetic, anti
      hypertensive and hypolipidemic foods.

PMID- 22142358
TI  - Supercurrent and multiple Andreev reflections in an InSb nanowire Josephson
      junction.
AB  - Epitaxially grown, high quality semiconductor InSb nanowires are emerging
      material systems for the development of high performance nanoelectronics and
      quantum information processing and communication devices and for the studies of
      new physical phenomena in solid state systems. Here, we report on measurements of
      a superconductor-normal conductor-superconductor junction device fabricated from
      an InSb nanowire with aluminum-based superconducting contacts. The measurements
      show a proximity-induced supercurrent flowing through the InSb nanowire segment
      with a critical current tunable by a gate in the current bias configuration and
      multiple Andreev reflection characteristics in the voltage bias configuration.
      The temperature dependence and the magnetic field dependence of the critical
      current and the multiple Andreev reflection characteristics of the junction are
      also studied. Furthermore, we extract the excess current from the measurements
      and study its temperature and magnetic field dependences. The successful
      observation of the superconductivity in the InSb nanowire-based Josephson
      junction device indicates that InSb nanowires provide an excellent material
      system for creating and observing novel physical phenomena such as Majorana
      fermions in solid-state systems.

PMID- 22142360
TI  - Analysing family service needs of typically underserved families in the USA.
AB  - BACKGROUND: Present day service systems evolved from the traditional model of
      disability intervention where the child with the disability and the family were
      viewed as pathological entities that needed to be fixed rather than supported.
      Scholars have increasingly called for a greater focus on the family in service
      delivery, but few studies have empirically examined the practical reality of such
      a shift. The present paper examines the disability-related formal service
      supports within the family quality of life (FQOL) framework in a sample of
      predominantly low-income, minority families in the USA. METHODS: Cross-sectional
      data collected from a convenience sample of 149 families using the Family Quality
      of Life Survey (FQOLS-2006) was analysed at the univariate, bivariate and
      multivariate levels. RESULTS: Over half of the families indicated that they
      needed more help from the service system, and the largest barrier to accessing
      services was a lack of information. Almost all families viewed service support as
      very important to their overall FQOL; however, only half of them were satisfied
      with the formal support that they were receiving. Less than half of the families
      reported having many service support opportunities and high attainment of service
      support, although most took high initiative in pursuing formal supports. The path
      model illustrated the complex inter-relationships between the six dimensions of
      service support. CONCLUSIONS: Findings underscore the need for resources to
      empower families and the value of using the FQOLS-2006 to ascertain the service
      support needs and strengths of families.

PMID- 22142359
TI  - Mood and motor trajectories in Parkinson's disease: multivariate latent growth
      curve modeling.
AB  - OBJECTIVE: Apathy is a common feature of Parkinson's disease (PD) that can
      manifest independently of depression, but little is known about its natural
      progression in medically managed patients. The present study sought to
      characterize and compare trajectories of apathy, depression, and motor symptoms
      in PD over 18 months. METHOD: Data from a sample of 186 PD patients (mean disease
      duration of 8.2 years) followed by the University of Florida Movement Disorders
      Center were obtained from a clinical research database. Scores on the Unified
      Parkinson's disease Rating Scale (motor portion), Apathy Scale, and Beck
      Depression Inventory at three time-points (baseline, 6 months, 18 months) were
      analyzed in a structural equation modeling framework. RESULTS: A multivariate
      growth model controlling for age, sex, education, and disease duration identified
      linear worsening of both apathy (slope estimate = 0.73; p < .001) and motor
      symptoms (slope estimate = 1.51; p < .001), and quadratic changes in depression
      (slope estimate = 1.18; p = .07). All symptoms were positively correlated. Higher
      education was associated with lower apathy, depression, and motor severity.
      Advanced age was associated with greater motor and apathy severity. Female sex
      and longer disease duration were associated with attenuated motor worsening.
      Antidepressant use was associated only with depression scores. CONCLUSIONS: These
      longitudinal results support the differentiation of apathy and depression in PD.
      Like motor progression, apathy progression may be linked at least partially to
      dopaminergic neurodegeneration. Empirically supported treatments for apathy in PD
      are needed.

PMID- 22142361
TI  - Processes underlying treatment success and failure in assertive community
      treatment.
AB  - BACKGROUND: Processes underlying success and failure in assertive community
      treatment (ACT), a widely investigated treatment model for persons with severe
      mental illness, are poorly understood. AIMS: The purpose of the current study was
      to examine processes in ACT by (1) understanding how consumers and staff describe
      the processes underlying treatment success and failure and (2) comparing
      processes identified by staff and consumers. METHOD: Investigators conducted semi
      structured interviews with 25 staff and 23 consumers from four ACT teams.
      RESULTS: Both staff and consumers identified aspects of the ACT team itself as
      the most critical in the process of consumer success. For failure, consumers
      identified consumer characteristics as most critical and staff identified lack of
      social relationships. Processes underlying failure were not viewed as merely the
      opposite of processes underlying success. In addition, there was notable
      disagreement between staff and consumers on important processes. CONCLUSIONS:
      Findings overlap with critical ingredients identified in previous studies,
      including aspects of the ACT team, social involvement and employment. In contrast
      to prior studies, there was little emphasis on hospitalizations and greater
      emphasis on not abusing substances, obtaining wants and desires, and consumer
      characteristics.

PMID- 22142363
TI  - Bidirectional transport of organelles: unity and struggle of opposing motors.
AB  - Bidirectional transport along microtubules is ensured by opposing motor proteins:
      cytoplasmic dynein that drives cargo to the minus-ends and various kinesins that
      generally move to the plus-ends of microtubules. Regulation of motor proteins
      that are simultaneously bound to the same organelle is required to maintain
      directional transport and prevent pausing of cargo pulled away by motors of
      opposite polarity. Debates of the recent decade have been focused on two possible
      mechanisms of such regulation: (i) coordination, which implies that only one type
      of motors is active at a given time, and (ii) tug-of-war, which assumes that both
      motors are active at the same time and that direction of transport depends on the
      outcome of motor's confrontation. The initial idea of coordination has been
      challenged by observations of simultaneous activity of plus- and minus-end
      directed motors applied to the same cargo. Analysis of the available data
      indicates that coordination and tug-of-war theories rather complement than
      contradict each other: cargo interacts with two teams of active motors, the
      resulting direction and the winner team are determined by coordination complexes,
      but the activity of the loser team is never completely inhibited and remains at
      some background level. Such persisting activity might enhance the overall
      efficiency of transport by increasing processivity or helping to overcome the
      obstacles on microtubule track.

PMID- 22142362
TI  - Coumarin 314 free radical cation: formation, properties, and reactivity toward
      phenolic antioxidants.
AB  - We have explored the photogeneration of the coumarin 314 radical cation by using
      nanosecond laser excitation at wavelengths longer than 400 nm in benzene,
      acetonitrile, dichloromethane, and aqueous media. In addition, time-resolved
      absorption spectroscopy measurements allowed detection of the triplet excited
      state of coumarin 314 (C(314)) with a maximum absorption at 550 nm in benzene.
      The triplet excited state has a lifetime of 90 MUs in benzene. It is readily
      quenched by oxygen (k(q) = 5.0 * 10(9) M(-1) s(-1)). From triplet-triplet energy
      transfer quenching experiments, it is shown that the energy of this triplet
      excited state is higher than 35 kcal/mol, in accord with the relatively large
      singlet oxygen quantum yield (Phi(Delta) = 0.25). However, in aqueous media, the
      coumarin triplet was no longer observed, and instead of that, a long-lived (160
      MUs in air-equilibrated solutions) free radical cation with a maximum absorbance
      at 370 nm was detected. The free radical cation generation, which has a quantum
      yield of 0.2, occurs by electron photoejection. Moreover, density functional
      theory (DFT) calculations indicate that at least 40% of the electronic density is
      placed on the nitrogen atom in aqueous media, which explains its lack of
      reactivity toward oxygen. On the other hand, rate constant values close to the
      diffusion rate limit in water (>10(9) M(-1) s(-1)) were found for the quenching
      of the C(314) free radical cation by phenolic antioxidants. The results have been
      interpreted by an electron-transfer reaction between the phenolic antioxidant and
      the radical cation where ion pair formation could be involved.

PMID- 22142364
TI  - UV radiation induces the release of angiopoietin-2 from dermal microvascular
      endothelial cells.
AB  - In human skin, ultraviolet radiation (UVR)-induced erythema is characterized by
      the inflammatory and angiogenic activation of dermal endothelial cells. Recently,
      it has been shown that the release of angiopoietin-2 (Ang-2) from cytoplasmic
      storages of activated endothelial cells is crucial for the induction of
      inflammation and angiogenesis. Therefore, we hypothesized that UVR exposure
      induces the release of Ang-2 from endothelial cells controlling the early steps
      of erythema formation. In an in vivo study, suction blister fluids generated from
      UV-irradiated skin showed significantly increased concentrations of Ang-2,
      vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha
      (TNFalpha). Likewise, in vitro UVR exposure of human dermal microvascular
      endothelial cells (HDMECs) triggered the release of Ang-2 that enhanced the pro
      inflammatory response of these cells and facilitated their detachment from smooth
      muscle cells as evidenced by employing a three-dimensional co-culture spheroid
      model. These effects were inhibited by angiopoietin-1 (Ang-1), which competes
      with Ang-2 for binding the endothelial cell Tie2 receptor. Collectively, these
      observations suggest that UVR triggers the release of endothelial Ang-2 which may
      promote the destabilization and pro-inflammatory phenotype of the microvascular
      endothelium. As Ang-1 counteracts UVR-induced effects, stimulating the Ang-1
      activity may represent a strategy to stabilize the dermal microcirculatory
      system, thus protecting against UVR-induced skin damages.

PMID- 22142365
TI  - A Partial Least Squares based algorithm for parsimonious variable selection.
AB  - BACKGROUND: In genomics, a commonly encountered problem is to extract a subset of
      variables out of a large set of explanatory variables associated with one or
      several quantitative or qualitative response variables. An example is to identify
      associations between codon-usage and phylogeny based definitions of taxonomic
      groups at different taxonomic levels. Maximum understandability with the smallest
      number of selected variables, consistency of the selected variables, as well as
      variation of model performance on test data, are issues to be addressed for such
      problems. RESULTS: We present an algorithm balancing the parsimony and the
      predictive performance of a model. The algorithm is based on variable selection
      using reduced-rank Partial Least Squares with a regularized elimination. Allowing
      a marginal decrease in model performance results in a substantial decrease in the
      number of selected variables. This significantly improves the understandability
      of the model. Within the approach we have tested and compared three different
      criteria commonly used in the Partial Least Square modeling paradigm for variable
      selection; loading weights, regression coefficients and variable importance on
      projections. The algorithm is applied to a problem of identifying codon
      variations discriminating different bacterial taxa, which is of particular
      interest in classifying metagenomics samples. The results are compared with a
      classical forward selection algorithm, the much used Lasso algorithm as well as
      Soft-threshold Partial Least Squares variable selection. CONCLUSIONS: A
      regularized elimination algorithm based on Partial Least Squares produces results
      that increase understandability and consistency and reduces the classification
      error on test data compared to standard approaches.

PMID- 22142366
TI  - Flunarizine for the prevention of migraine - a new look at an old drug.

PMID- 22142367
TI  - The natural cell-penetrating peptide crotamine targets tumor tissue in vivo and
      triggers a lethal calcium-dependent pathway in cultured cells.
AB  - Our goal was to demonstrate the in vivo tumor specific accumulation of crotamine,
      a natural peptide from the venom of the South American rattlesnake Crotalus
      durissus terrificus, which has been characterized by our group as a cell
      penetrating peptide with a high specificity for actively proliferating cells and
      with a concentration-dependent cytotoxic effect. Crotamine cytotoxicity has been
      shown to be dependent on the disruption of lysosomes and subsequent activation of
      intracellular proteases. In this work, we show that the cytotoxic effect of
      crotamine also involves rapid intracellular calcium release and loss of
      mitochondrial membrane potential as observed in real time by confocal microscopy.
      The intracellular calcium overload induced by crotamine was almost completely
      blocked by thapsigargin. Microfluorimetry assays confirmed the importance of
      internal organelles, such as lysosomes and the endoplasmic reticulum, as
      contributors for the intracellular calcium increase, as well as the extracellular
      medium. Finally, we demonstrate here that crotamine injected intraperitoneally
      can efficiently target remote subcutaneous tumors engrafted in nude mice, as
      demonstrated by a noninvasive optical imaging procedure that permits in vivo real
      time monitoring of crotamine uptake into tumor tissue. Taken together, our data
      indicate that the cytotoxic peptide crotamine can be used potentially for a dual
      purpose: to target and detect growing tumor tissues and to selectively trigger
      tumor cell death.

PMID- 22142368
TI  - Impact of dust from multiple microenvironments and diet on PentaBDE body burden.
AB  - Our objectives were to determine relative contributions of diet and dust exposure
      from multiple microenvironments to PentaBDE body burden, and to explore the role
      of handwipes as a measure of personal exposure to PentaBDE. We administered a
      food frequency questionnaire and collected serum, dust (office, main living area,
      bedroom, and vehicle), and handwipe samples from 31 participants. SigmaPentaBDEs
      (sum of BDE 28/33, 47, 99, 100, and 153) in handwipes collected in the office
      environment were weakly correlated with dust collected from offices (r = 0.35, p
      = 0.06) and bedrooms (r = 0.39, p = 0.04), but not with dust from main living
      areas (r = -0.05, p = 0.77) or vehicles (r = 0.17, p = 0.47). SigmaPentaBDEs in
      serum were correlated with dust from main living areas (r = 0.42, p = 0.02) and
      bedrooms (r = 0.49, p = 0.008), but not with dust from offices (r = 0.22, p =
      0.25) or vehicles (r = 0.20, p = 0.41). Our final regression model included
      variables for main living area dust and handwipes, and predicted 55% of the
      variation in serum SigmaPentaBDE concentrations (p = 0.0004). Diet variables were
      not significant predictors of SigmaPentaBDEs in serum. Our research suggests that
      exposure to dust in the home environment may be the most important factor in
      predicting PentaBDE body burden in North Americans, and potential exposure
      pathways may involve PBDE residues on hands.

PMID- 22142369
TI  - International practice patterns and factors associated with non-conventional
      hemodialysis utilization.
AB  - BACKGROUND: The purpose of our study was to determine characteristics that
      influence the utilization of non-conventional hemodialysis (NCHD) therapies and
      its subtypes (nocturnal (NHD), short daily (SDHD), long conventional (LCHD) and
      conventional hemodialysis (CHD) as well as provider attitudes regarding the
      evidence for NCHD use. METHODS: An international cohort of subscribers of a
      nephrology education website http://www.nephrologynow.com was invited to
      participate in an online survey. Non-conventional hemodialysis was defined as any
      forms of hemodialysis delivered > 3 treatments per week and/or > 4 hours per
      session. NHD and SDHD included both home and in-centre. Respondents were
      categorized as CHD if their centre only offered conventional thrice weekly
      hemodialysis. Variables associated with NCHD and its subtypes were determined
      using multivariate logistic regression analysis. The survey assessed multiple
      domains regarding NCHD including reasons for initiating and discontinuing, for
      not offering and attitudes regarding evidence. RESULTS: 544 surveys were
      completed leading to a 15.6% response rate. The final cohort was limited to 311
      physicians. Dialysis modalities utilized among the respondents were as follows:
      NCHD194 (62.4%), NHD 83 (26.7%), SDHD 107 (34.4%), LCHD 81 (26%) and CHD 117
      (37.6%). The geographic regions of participants were as follows: 11.9% Canada,
      26.7% USA, 21.5% Europe, 6.1% Australia/New Zealand, 10% Africa/Middle East,
      10.9% Asia and 12.9% South America. Variables associated with NCHD utilization
      included NCHD training (OR 2.47 CI 1.25-4.16), government physician reimbursement
      (OR 2.66, CI 1.11-6.40), practicing at an academic centre (OR 2.28 CI 1.25-4.16),
      higher national health care expenditure and number of ESRD patients per centre.
      Hemodialysis providers with patients on NCHD were significantly more likely to
      agree with the statements that NCHD improves quality of life, improves
      nutritional status, reduces EPO requirements and is cost effective. The most
      common reasons to initiate NCHD were driven by patient preference and the desire
      to improve volume control and global health outcomes. CONCLUSION: Physician
      attitudes toward the evidence for NCHD differ significantly between NCHD
      providers and conventional HD providers. Interventions and health policy
      targeting these areas along with increased physician education and training in
      NCHD modalities may be effective in increasing its utilization.

PMID- 22142371
TI  - Bilateral superficial cervical plexus block in combination with general
      anesthesia has a low efficacy in thyroid surgery: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: A combination of bilateral superficial cervical plexus block (BSCPB)
      and general anesthesia is recommended for thyroid surgery. Proof of the efficacy
      of this combination remains weak. Furthermore, data on the safety of this regimen
      are lacking. Therefore, a meta-analysis of randomized controlled trials (RCT) to
      evaluate the efficacy and safety of BSCPB as an adjunct to general anesthesia in
      patients receiving thyroid surgery was performed. METHODS: A meta-analysis of RCT
      was performed that included interventional groups evaluating the efficacy of
      BSCPB 6 and 24 hours after thyroid surgery. RESULTS: Eight RCT, including a total
      of 799 patients (463 who underwent BSCPB and 336 controls), were analyzed. A meta
      analysis demonstrated a reduction in pain scores 6 hours (Hedges' g: -0.46 [95%
      CI: -0.74 to -0.19]; p=0.001) and 24 hours postoperatively (Hedges' g: -0.49 [95%
      CI: -0.71 to -0.27]; p<0.001) in patients who had undergone BSCPB. The relative
      risk for postoperative nausea and vomiting (PONV) was 0.80 (95% CI: 0.58 to 1.09,
      p=0.159) in patients receiving BSCPB. Procedure-related adverse events were
      reported in three of the 476 patients who had undergone BSCPB (0.6%; 95% CI: 0.1%
      to 2.0%). These three patients had transient paresis of the brachial plexus,
      combined with a diaphragmatic paresis in one case, and all spontaneously
      resolved. CONCLUSION: The combination of BSCPB and general anesthesia has a
      significant benefit in reducing pain 6 and 24 hours after thyroid surgery.
      However, the effect on pain reduction is too small to be of clinical relevance.
      Although it is a safe procedure, the existing evidence allows for no
      recommendation concerning the application of BSCPB in thyroid surgery. Further
      trials should evaluate a dose-response relationship and the incidence of PONV
      with this regimen.

PMID- 22142372
TI  - Association analyses of variants in the DIO2 gene with early-onset type 2
      diabetes mellitus in Pima Indians.
AB  - BACKGROUND: The type 2 deiodinase gene (DIO2) encodes a deiodinase that converts
      the thyroid prohormone, thyroxine, to the biologically active triiodothyronine.
      Thyroid hormones regulate energy balance and may also influence glucose
      metabolism. Therefore, we hypothesized that variations in DIO2 could contribute
      to obesity or type 2 diabetes mellitus (T2DM) in Pima Indians. METHODS:
      Sequencing of the DIO2 gene in DNA from 83 Pima Indians identified 12 single
      nucleotide polymorphisms (SNPs). Several of these SNPs were in perfect genotypic
      concordance among the 83 samples that were sequenced, and all 12 could be divided
      into five linkage disequilibrium groups. One representative SNP from each group
      (Thr92Ala, rs225011, rs225015, rs6574549, and a rare 5' flanking SNP) was
      selected for further genotyping for association analyses. In this study, the five
      selected variants in DIO2, as described above, were genotyped in three groups of
      Pima Indians: (i) a case (n=150)/control (n=150) group for early-onset T2DM
      (onset age <25 years); (ii) a case (n=362)/control (n=127) group for obesity;
      (iii) a large (n=1,311, cases n=810/controls n=501) family-based group, of which
      256 nondiabetic subjects had undergone detailed metabolic phenotyping. RESULTS:
      The Thr92Ala variant common in Pima Indians, rs225011, and rs225015 were modestly
      associated with early-onset T2DM (p=0.01-0.04) in the case-control study, but
      were not associated with obesity in the obesity case-control study, nor
      associated with T2DM (at any age) or body-mass index (BMI; as a quantitative
      trait) in the family-based analysis. Thr92Ala, rs225011, rs225015, and rs6574549
      were also nominally associated with hepatic glucose output (p=0.02). rs6574549
      was associated with fasting insulin (p=0.02), insulin action (p=0.04), and energy
      expenditure (p=0.02). None of these nominal associations remained statistically
      significant after corrections for multiple testing. CONCLUSIONS: We propose that
      variation in DIO2 may have a subtle role in altering metabolic processes that
      lead to early-onset T2DM, but this gene does not have a large impact on T2DM at
      older ages, nor does DIO2 influence BMI in the Pima Indian population.

PMID- 22142373
TI  - Factors associated with the development of new onset diffuse thyroid F18
      fluorodeoxyglucose uptake after treatment of breast cancer in patients without a
      history of thyroid disease or thyroid dysfunction.
AB  - BACKGROUND: Many studies have shown an association between thyroid disorders and
      breast cancer. Among them, diffusely increased thyroid uptake of F18
      fluorodeoxyglucose (F-18 FDG) has been associated with chronic lymphocytic
      thyroiditis. There is little or no information regarding the relationship between
      treatment of breast cancer and the development of new diffuse thyroid F-18 FDG
      uptake. Here, we report the frequency of this occurrence and some of the factors
      associated with it. METHODS: We performed a retrospective review of the positron
      emission tomography (PET) computed tomography (CT) database and identified 290
      women who had underwent PET-CTs both before and after breast surgery. Of these,
      246 were enrolled in this study and 44 were excluded, because before breast
      surgery they had either a history of prior thyroid disorders including thyroid
      cancer or abnormal serum free thyroxine and thyroid-stimulating hormone, or other
      malignancies. Tests for serum antithyroid antibodies were not available before
      thyroid surgery in all patients. There were 62 patients who did have antithyroid
      antibody tests before surgery and 27 were positive. They were not excluded from
      the study. RESULTS: Diffuse thyroidal uptake on PET-CT developed in 23 (9.3%)
      patients during the follow-up period (median=21.1 months; range=3.1-47.3 months).
      Age (>=55 years; hazard ratio [HR]=0.15; 95% confidence interval [CI]: 0.03-0.65;
      p=0.012), bilaterality of breast cancer (HR=3.87; 95% CI: 1.02-14.62; p=0.046),
      and postsurgical radiotherapy (HR=3.06; 95% CI: 1.03-9.16; p=0.045) showed
      independent association with new thyroid FDG uptake in multivariate analysis. All
      patients with thyroid FDG uptake met at least one of some criteria related to
      chronic thyroditis (positive for antithyroid antibodies or cytology findings or
      ultrasonography findings of Hashimoto's thyroiditis) and were associated with
      development of hypothyroidism (52.2% vs. 4.5% in patients without uptake;
      p<0.001). CONCLUSIONS: Radiotherapy in breast cancer may be an independent
      predictive factor for the development of new diffuse thyroidal uptake in PET-CT
      associated with thyroid dysfunction during follow-up. The development of diffuse
      F-18 FDG uptake is a marker for thyroid abnormalities. Younger women who have
      radiotherapy after surgery for breast cancer, in particular, are candidates for
      close follow-up of their thyroid function.

PMID- 22142374
TI  - Kinetic studies to investigate lipoprotein metabolism.
AB  - To develop novel strategies for the prevention and treatment of dyslipidaemia, it
      is essential to understand the pathophysiology of dyslipoproteinaemia in humans.
      Lipoprotein metabolism is a complex system in which abnormal concentrations of
      various lipoprotein particles can result from alterations in their rates of
      production, conversion and/or catabolism. Traditional methods that measure plasma
      lipoprotein concentrations only provide static estimates of lipoprotein
      metabolism and hence limited mechanistic information. By contrast, the use of
      tracers labelled with stable isotopes and mathematical modelling provides a
      powerful tool for probing lipid and lipoprotein kinetics in vivo and furthering
      understanding of the pathogenesis of dyslipoproteinaemia.

PMID- 22142375
TI  - Severe acute liver injury associated with lumiracoxib.
AB  - BACKGROUND AND AIM: Significant elevations in liver transaminases were noted in
      some patients during pre-marketing clinical trials with lumiracoxib, a selective
      COX-2 inhibitor. It was withdrawn from the Australian market in August 2007,
      because of an association with severe liver injury. We describe in detail three
      cases of severe liver injury in patients taking lumiracoxib METHODS: Three
      patients admitted to our hospital with severe liver injury and taking lumiracoxib
      are described in detail, together with information on a further six cases
      reported to the Australian Therapeutics Goods Administration (TGA), none of whom
      had pre-existing liver disease or obvious risk factors for liver disease.
      RESULTS: Liver histology showed severe hepatic necrosis. One patient required
      liver transplantation and another died. Autoantibodies were detected in all three
      patients. As with the other six cases reported to the TGA, all were females who
      had been taking lumiracoxib 200-400 mg daily, typically for a few months, for
      osteoarthritis. CONCLUSIONS: Lumiracoxib can be associated with severe liver
      injury. The presence of a variety of positive auto-antibodies suggests an altered
      immune response may be contributory.

PMID- 22142376
TI  - Evolution of care pathway for laparoscopic radical prostatectomy.
AB  - PURPOSE: We report results of the introduction of a laparoscopic radical
      prostatectomy (LRP) care pathway. This included the introduction of a transversus
      abdominis plane (TAP) local anesthetic block and other measures to reduce the
      impact of factors known to delay postoperative recovery. Outcomes including pain,
      analgesic requirements, complications, and length of stay are reported. PATIENTS
      AND METHODS: Two hundred consecutive patients undergoing LRP from 2008 to 2010
      were prospectively studied. A detailed perioperative care pathway was developed
      and implemented. The pathway was modified after a pain audit to include bilateral
      transversus abdominis plane regional anesthetic blockade. Same day discharge
      criteria were applied to suitable patients. Demographics and perioperative and
      follow-up data were prospectively collected and recorded on a database. RESULTS:
      Overall, 78% of cases were discharged after 1 night stay; 14 patients were
      managed as true day cases without overnight stay. Operative time (P<0.0001),
      intraoperative blood loss (P=0.018), %<= 1 day stay (P=0.0091), transfusion, and
      conversion rate (nil in latter 100 cases) all improved significantly in the
      second 100 group of patients compared with the first 100 cases. The introduction
      of TAP blocks led to significant reductions of mean intraoperative and
      postoperative opiate use (17.3 mg to 1.3 mg and 1.9 mg to 0.2 mg morphine,
      respectively) without any significant effect on perceived pain. True day cases
      did not experience a significantly different rate of complications than the whole
      cohort. CONCLUSIONS: Through a structured care pathway incorporating the TAP
      block, 1 night stay laparoscopic prostatectomy can be safely delivered with
      reduced inpatient stay costs. In selected patients, day-case prostatectomy is
      feasible.

PMID- 22142377
TI  - Analysis of allergen immunotherapy studies shows increased clinical efficacy in
      highly symptomatic patients.
AB  - BACKGROUND: The assessment of allergen immunotherapy (AIT) efficacy in the
      treatment for seasonal allergic rhinoconjunctivitis (SAR) symptoms is
      challenging. Allergen immunotherapy differs from symptomatic therapy in that
      while symptomatic therapy treats patients after symptoms appear and aims to
      reduce symptoms, AIT is administered before symptoms are present and aims to
      prevent them. Thus, clinical studies of AIT can neither establish baseline
      symptom levels nor limit the enrolment of patients to those with the most severe
      symptoms. Allergen immunotherapy treatment effects are therefore diluted by
      patients with low symptoms for a particular pollen season. The objective of this
      analysis was to assess the effect possible to achieve with AIT in the groups of
      patients presenting the most severe allergic symptoms. METHODS: Study centres
      were grouped into tertiles categorized according to symptom severity scores
      observed in the placebo patients in each centre (low, middle and high tertiles).
      The difference observed in the average score in each tertile in active vs placebo
      treated patients was assessed. This allowed an estimation of the efficacy that
      could be achieved in patients from sites where symptoms were high during the
      pollen season. RESULTS: An increased treatment effect was observed in the most
      severe patients and was independent of the study analysed and symptom score used.
      CONCLUSIONS: The use of a tertile approach to analyse efficacy in AIT in SAR
      clinical studies can give a more accurate assessment of potential clinical
      benefit.

PMID- 22142380
TI  - Air pollution and chronic obstructive pulmonary disease.
AB  - Limited data suggest that outdoor air pollution (such as ambient air pollution or
      traffic-related air pollution) and indoor air pollution (such as second-hand
      smoking and biomass fuel combustion exposure) are associated with the development
      of chronic obstructive pulmonary disease (COPD), but there is insufficient
      evidence to prove a causal relationship at this stage. It also appears that
      outdoor air pollution is a significant environmental trigger for acute
      exacerbation of COPD, leading to increasing symptoms, emergency department
      visits, hospital admissions and even mortality. Improving ambient air pollution
      and decreasing indoor biomass combustion exposure by improving home ventilation
      are effective measures that may substantially improve the health of the general
      public.

PMID- 22142378
TI  - Identification of formation of initial native structure in onconase from an
      unfolded state.
AB  - In the oxidative folding of onconase, the stabilization of intermediates early in
      the folding process gives rise to efficient formation of its biologically active
      form. To identify the residues responsible for the initial formation of
      structured intermediates, the transition from an ensemble of unstructured three
      disulfide species, 3S(U), to a single structured three-disulfide intermediate
      species, des-[30-75] or 3S(F), at pH 8.0 and 25  degrees C was examined. This
      transition was first monitored by far-UV circular dichroism spectroscopy at pH
      8.0 and 25  degrees C, showing that it occurs with the formation of secondary
      structure, presumably because of native interactions. The time dependence of
      formation of nativelike structure was then followed by nuclear magnetic resonance
      spectroscopy after we had arrested the transition at different times by lowering
      the pH to 3 and then acquiring (1)H-(15)N heteronuclear single-quantum coherence
      spectra at pH 3 and 16  degrees C to identify amide hydrogens that become part of
      nativelike structure. H/D exchange was utilized to reduce the intensity of
      resonances from backbone amide hydrogens not involved in structure, without
      allowing exchange of backbone amide hydrogens involved in initial structure. Six
      hydrogen-bonding residues, namely, Tyr38, Lys49, Ser82, Cys90, Glu91, and Ala94,
      were identified as being involved in the earliest detectable nativelike structure
      before complete formation of des-[30-75] and are further stabilized later in the
      formation of this intermediate through S-S/SH interchange. By observing the
      stabilization of the structures of these residues by their neighboring residues,
      we have identified the initial, nativelike structural elements formed in this
      transition, providing details of the initial events in the oxidative folding of
      onconase.

PMID- 22142381
TI  - Management of complex regional pain syndrome type I in upper extremity-evaluation
      of continuous stellate ganglion block and continuous infraclavicular brachial
      plexus block: a pilot study.
AB  - Interventional pain management techniques play an important role in the
      multidisciplinary approach to management of complex regional pain syndrome
      (CRPS). In this preliminary study we compared the efficacy of continuous stellate
      ganglion (CSG) block with that of continuous infraclavicular brachial plexus
      (CIBP) block in management of CRPS type I of upper extremity. METHODS: Thirty
      three patients with CRPS type I of upper extremity were randomly assigned to
      either CSG or CIBP group. Patients were treated for 1 week with continuous
      infusion of 0.125% bupivacaine at 2and 5mL/h, respectively. Catheter was removed
      at 1 week and patients were followed up for 4 weeks. The outcome was evaluated in
      terms of neuropathic pain scale score (NPSS), edema scores (Grades 0-2), and
      range of motion (ROM) of all upper extremity joints (Grades 0-2). RESULTS: CIBP
      group showed statistically significant improvement in NPSS compared with CSG
      group during the first 12 hours after the procedures (P value <0.05). After 12
      hours, the NPSS was comparable between the groups. At 4 weeks, both groups showed
      clinically significant improvement in edema score and ROM of all upper extremity
      joints when compared with the baseline. CONCLUSION: This preliminary study
      suggests that CIBP block and CSG block may be feasible and effective
      interventional techniques for the management of CRPS type I of upper extremities.
      Hence, we recommend a larger well-randomized, well-controlled, clinical trial to
      confirm our findings and determine if any significant difference exists between
      the groups in terms of long-term pain relief and functional restoration.

PMID- 22142382
TI  - Oral bioavailability of the ether lipid plasmalogen precursor, PPI-1011, in the
      rabbit: a new therapeutic strategy for Alzheimer's disease.
AB  - INTRODUCTION: Docosahexaenoic acid (DHA) and DHA-containing ethanolamine
      plasmalogens (PlsEtn) are decreased in the brain, liver and the circulation in
      Alzheimer's disease. Decreased supply of plasmalogen precursors to the brain by
      the liver, as a result of peroxisomal deficits is a process that probably starts
      early in the AD disease process. To overcome this metabolic compromise, we have
      designed an orally bioavailable DHA-containing ether lipid precursor of
      plasmalogens. PPI-1011 is an alkyl-diacyl plasmalogen precursor with palmitic
      acid at sn-1, DHA at sn-2 and lipoic acid at sn-3. This study outlines the oral
      pharmacokinetics of this precursor and its conversion to PlsEtn and
      phosphatidylethanolamines (PtdEtn). METHODS: Rabbits were dosed orally with PPI
      1011 in hard gelatin capsules for time-course and dose response studies.
      Incorporation into PlsEtn and PtdEtn was monitored by LC-MS/MS. Metabolism of
      released lipoic acid was monitored by GC-MS. To monitor the metabolic fate of
      different components of PPI-1011, we labeled the sn-1 palmitic acid, sn-2 DHA and
      glycerol backbone with (13)C and monitored their metabolic fates by LC-MS/MS.
      RESULTS: PPI-1011 was not detected in plasma suggesting rapid release of sn-3
      lipoic acid via gut lipases. This conclusion was supported by peak levels of
      lipoic acid metabolites in the plasma 3 hours after dosing. While PPI-1011 did
      not gain access to the plasma, it increased circulating levels of DHA-containing
      PlsEtn and PtdEtn. Labeling experiments demonstrated that the PtdEtn increases
      resulted from increased availability of DHA released via remodeling at sn-2 of
      phospholipids derived from PPI-1011. This release of DHA peaked at 6 hrs while
      increases in phospholipids peaked at 12 hr. Increases in circulating PlsEtn were
      more complex. Labeling experiments demonstrated that increases in the target
      PlsEtn, 16:0/22:6, consisted of 2 pools. In one pool, the intact precursor
      received a sn-3 phosphoethanolamine group and desaturation at sn-1 to generate
      the target plasmalogen. The second pool, like the PtdEtn, resulted from increased
      availability of DHA released during remodeling of sn-2. In the case of sn-1 18:0
      and 18:1 plasmalogens with [(13)C(3)]DHA at sn-2, labeling was the result of
      increased availability of [(13)C(3)]DHA from lipid remodeling. Isotope and
      repeated dosing (2 weeks) experiments also demonstrated that plasmalogens and/or
      plasmalogen precursors derived from PPI-1011 are able to cross both the blood
      retinal and blood-brain barriers. CONCLUSIONS: Our data demonstrate that PPI
      1011, an ether lipid precursor of plasmalogens is orally bioavailable in the
      rabbit, augmenting the circulating levels of unesterified DHA and DHA-containing
      PlsEtn and PtdEtn. Other ethanolamine plasmalogens were generated from the
      precursor via lipid remodeling (de-acylation/re-acylation reactions at sn-2) and
      phosphatidylethanolamines were generated via de-alkylation/re-acylation reactions
      at sn-1. Repeated oral dosing for 2 weeks with PPI-1011 resulted in dose
      dependent increases in circulating DHA and DHA-containing plasmalogens. These
      products and/or precursors were also able to cross the blood-retinal and blood
      brain barriers.

PMID- 22142383
TI  - Optimizing cross-reactivity with evolutionary search for sensors.
AB  - We report a straightforward evolutionary procedure to build an optimal sensor
      array from a pool of DNA sequences oriented toward three-way junctions. The
      individual sensors were mined from this pool under separate selection pressures
      to interact with four steroids, while allowing cross-reactivity, in a manner
      designed to achieve perfect classification of individual steroids. The resulting
      sensor array had three sensors and displayed discriminatory capacity between
      steroid classes over full ranges of concentrations. We propose that similar
      protocols can be used whenever we have two or more classes of samples, with
      individual classes being defined through gross differences in ratios of dominant
      families of responsive components.

PMID- 22142384
TI  - Confinement-guided shaping of semiconductor nanowires and nanoribbons: "writing
      with nanowires".
AB  - To fully exploit their full potential, new semiconductor nanowire building blocks
      with ab initio controlled shapes are desired. However, and despite the great
      synthetic advances achieved, the ability to control nanowire's geometry has been
      significantly limited. Here, we demonstrate a simple confinement-guided nanowire
      growth method that enables to predesign not only the chemical and physical
      attributes of the synthesized nanowires but also allows a perfect and unlimited
      control over their geometry. Our method allows the synthesis of semiconductor
      nanowires in a wide variety of two-dimensional shapes such as any kinked
      (different turning angles), sinusoidal, linear, and spiral shapes, so that
      practically any desired geometry can be defined. The shape-controlled nanowires
      can be grown on almost any substrate such as silicon wafer, quartz and glass
      slides, and even on plastic substrates (e.g., Kapton HN).

PMID- 22142385
TI  - Preparing to get the most from the biennial world injury conferences: Safety 2012
      World Conference in Wellington, New Zealand.

PMID- 22142386
TI  - How many, powerfully?

PMID- 22142390
TI  - Effects of rotation of topical vitamin D3 in chronic plaque-type psoriasis.

PMID- 22142389
TI  - Risk profiles of subtypes of mild cognitive impairment: the sydney memory and
      ageing study.
AB  - OBJECTIVES: To compare the risk profiles of mild cognitive impairment (MCI)
      subtypes in a population-based elderly sample. DESIGN: Cross-sectional study.
      SETTING: The population-based Sydney Memory and Ageing Study. PARTICIPANTS: Seven
      hundred fifty-seven English-speaking, community-dwelling individuals without
      dementia aged 70 to 90. MEASUREMENTS: Comprehensive neuropsychological
      assessments were used to diagnose MCI and its subtypes, categorized as amnestic
      (aMCI) or nonamnestic (naMCI) and as single- (sdMCI) or multiple- (mdMCI) domain.
      Risk profiles were derived from sociodemographic; lifestyle; and cardiac,
      physical, mental, and general health data. Whole-sample and sex-specific
      comparisons between aMCI and naMCI and between mdMCI and sdMCI were made using
      age- (and sex-) adjusted multiple regressions comprising initially significant
      univariate factors. RESULTS: Risk factors for MCI were presence of the
      apolipoprotein E (APOE) epsilon4 allele, heart disease, high homocysteine, poor
      odor identification ability, low visual acuity, and lower mental activity. The
      odds of having naMCI rather than aMCI were lower with greater levels of social
      activity and greater if taking antihypertensives, the latter particularly in men.
      The odds of naMCI were greater in men taking antidepressants or with a longer 6
      meter walk time and in women with hypertension. The odds of having mdMCI rather
      than sdMCI were greater in participants with a history of depression or having
      the APOE epsilon4 allele. Greater odds of mdMCI were also associated with lower
      mental activity, particularly for women. For men, the odds of mdMCI were greater
      with the APOE epsilon4 allele and lower if diagnosed with high cholesterol.
      CONCLUSION: MCI subtypes exhibit distinctive, sex-dependent risk profiles. This
      is consistent with MCI subtypes having different etiologies and outcomes and
      supports the idea that subtyping MCI may offer predictive validity and clinical
      application.

PMID- 22142391
TI  - Inverted 'V' osteotomy excision arthroplasty for bony ankylosed elbows.
AB  - BACKGROUND: Bony ankylosis of elbow is challenging and difficult problem to
      treat. The options are excision arthroplasty and total elbow replacement. We
      report our midterm results on nine patients, who underwent inverted 'V' osteotomy
      excision arthroplasty in our hospital with good functional results. MATERIALS:
      Our case series includes 9 patients (seven males and two females) with the mean
      age of 34 years (13-56 years). Five patients had trauma, two had pyogenic
      arthritis, one had tuberculous arthritis, and one had pyogenic arthritis
      following surgical fixation. RESULTS: The average duration of follow up is 65
      months (45 months-80 months). The mean Mayo's elbow performance score (MEPS)
      preoperatively was 48 (35-70). The MEPS at final follow up was 80 (60-95). With
      no movement at elbow and fixed in various degrees of either flexion or extension
      preoperatively, the mean preoperative position of elbow was 64 degrees (30
      degrees to 100 degrees ). The mean post operative range of motion at final follow
      up was 27 degrees of extension (20-500), 116 degrees of flexion (1100-1300), and
      the arc of motion was 88 degrees (800-1000). One patient had ulnar nerve
      neuropraxia and another patient developed median nerve neuropraxia, and both
      recovered completely in six weeks. No patient had symptomatic instability of the
      elbow. All patients were asymptomatic except one patient, who had pain mainly on
      heavy activities. CONCLUSION: We conclude that inverted 'V' osteotomy excision
      arthroplasty is a viable option in the treatment of bony ankylosis of the elbow
      in young patients.

PMID- 22142392
TI  - Study time allocation deficit of older adults: the role of environmental support
      at encoding?
AB  - The present research evaluated both metacognitive and environmental support
      accounts of age-related changes in the way study time is adapted to task
      difficulty. The original aim was to examine whether providing environmental
      support at encoding would allow older adults to adjust their study time to the
      task difficulty by using effective encoding strategies. The difficulty of the
      learning task was manipulated by varying the strength of association of cue
      target pairs (i.e., weak vs. strong associates). This allowed us to measure
      metacognitive control in aging and, specifically, the ability to adjust study
      time according to task difficulty. The level of environmental support at encoding
      was manipulated to examine whether it could be used by older adults to adjust
      their study time according to the task difficulty. In contrast to the classical
      literature on the effect of aging on metacognitive control, we found that older
      adults were able to adjust their study time to task difficulty when environmental
      support was provided. Furthermore, providing encoding strategies with information
      about their effectiveness helped older adults adjust their study time to task
      difficulty optimally by improving their strategy use and compensating for their
      associative memory deficit.

PMID- 22142393
TI  - The effect of pimecrolimus on expression of genes associated with skin barrier
      dysfunction in atopic dermatitis skin lesions.
AB  - The mechanism of action of pimecrolimus (PIM) on atopic lesions is still under
      consideration. Thus far, we have evidence of its anti-inflammatory and
      immunomodulatory activity, and recent papers focus on its effect on epidermal
      barrier function. This study analysed changes in the expression of genes
      associated with skin barrier dysfunction in atopic dermatitis (AD) skin lesions
      after 2 weeks of exposure to PIM 1% cream. A real-time quantitative PCR analysis
      of selected epidermal differentiation complex genes and three alternative pathway
      keratins was performed in skin biopsies from 11 individuals with AD before and
      after PIM exposure. The real-time quantitative PCR analysis was compared to non
      lesional skin in the same patients. Involucrin, a small proline-rich region
      (SPRR) 2C gene, and alternative pathway keratin 16 showed significant over
      expression in lesional skin followed by significant decrease after PIM therapy.
      The SPRR1A gene, S100A9, and keratin 6A were also increased; however, the
      decrease after PIM treatment was not significant. The changes in S100 A2, A7 and
      A8 followed a similar course with borderline significance. SPRR4 had a
      significant decrease in expression in lesional versus non-lesional skin, which
      persisted after PIM treatment. No significant changes were detected in mRNA
      expression levels of filaggrin and loricrin. Our results suggest that PIM can be
      effective in restoring the epidermal barrier in patients with AD at least in part
      by its impact on expression of genes, which are important for the normal barrier
      function of skin.

PMID- 22142395
TI  - Being reliable: issues in determining the reliability and making sense of
      observations of adults with congenital deafblindness?
AB  - BACKGROUND: Most research into interactions with people who are congenitally
      deafblind involves observational data. In order for practitioners and researchers
      to have confidence in the findings of observational studies, researchers need to
      demonstrate that the processes employed are replicable and trustworthy. This
      paper draws on data from an observational study of adults with congenital
      deafblindness to illustrate issues in determining inter-rater reliability, and
      interpreting observational data. METHOD: Data from 34 10-min observations of
      adults with congenital deafblindness and their interactions with support staff
      were assessed for inter-rater reliability using percentage agreement calculated
      in three different ways and Cohen's kappa. RESULTS: Large variation resulted from
      the different ways in which inter-rater reliability was calculated, largely due
      to high levels of non-occurrence of many behaviours in the coding tool used.
      CONCLUSION: This study highlights the need to exercise caution when ascertaining
      the reliability of observational studies and demonstrates the value in using
      multiple methods for calculating inter-rater reliability. The paper concludes
      with an examination of the potential merits of using consensus coding in
      observational studies of interactions with people with congenital deafblindness
      or profound intellectual and multiple disabilities.

PMID- 22142394
TI  - Trp2 peptide vaccine adjuvanted with (R)-DOTAP inhibits tumor growth in an
      advanced melanoma model.
AB  - Previously we have shown cationic lipid (R)-DOTAP as the immunologically active
      enantiomer of the DOTAP racemic mixture, initiating complete tumor regression in
      an exogenous antigen model (murine cervical cancer model). Here, we investigate
      the use of (R)-DOTAP as an efficacious adjuvant delivering an endogenous antigen
      in an aggressive murine solid tumor melanoma model. (R)-DOTAP/Trp2 peptide
      complexes showed decreasing size and charge with increasing peptide
      concentration, taking a rod shape at highest concentrations. The particles were
      stable for 2 weeks at 4  degrees C. A dose of 75 nmol of Trp2 (formulated in (R)
      DOTAP) was able to show statistically significant tumor growth delay compared to
      lower doses of 5 and 25 nmol, which were no different than untreated tumors. (R)
      DOTAP/Trp2 (75 nmol) treated mice also showed increased T cell IFN-gamma
      secretion after restimulation with Trp2, as well as CTL activity in vivo. This
      vaccination group also showed the highest population of functionally active tumor
      infiltrating lymphocytes, indicated by IFN-gamma secretion after restimulation
      with Trp2. Thus, (R)-DOTAP has shown the ability to break tolerance as an
      adjuvant. Its activity to enhance immunogenicity of other tumor associated
      antigens should be studied further.

PMID- 22142396
TI  - Porphyrin protonation studied by magnetic circular dichroism.
AB  - Magnetic circular dichroism (MCD) spectroscopy provides valuable information
      about electronic excited states in molecules. The interpretation of spectra is
      however difficult, often requiring additional theoretical calculations to
      rationalize the observed signal. Recent developments in time-dependent density
      functional theory (TDDFT) bring hope that the applicability of MCD spectroscopy
      for chemical problems may be significantly extended. In this study, two modern
      analytical TDDFT implementations are compared and used to understand experimental
      MCD spectra of a model porphyrin system upon protonation. Changes in porphyrin
      geometry and electronic structure are related to MCD intensities by comparing the
      spectra of 5,10,15,20-tetraphenyl-21H,23H-porphyrintetrasulfonic acid (TPPS)
      measured at different pH values with the TDDFT calculations. Although the
      theoretical results slightly depended on the chosen exchange-correlation
      functional, the computations provided MCD curves that could well rationalize the
      experimental data. The protonation of the porphyrin core causes marked changes in
      the MCD spectrum, whereas the role of the substituents is limited. Also,
      different conformations of the porphyrin substituents cause relatively minor
      changes of the MCD pattern, mostly in the Soret region, where the porphine and
      phenyl electronic transitions start to mix. The solvent environment simulated by
      the dielectric model caused a shift (~20 nm) of the absorption bands but only
      minor variations in the absorption and MCD spectral shapes. The study thus
      demonstrates that the recently available first-principles interpretations of MCD
      spectra significantly enhance the applicability of the technique for molecular
      structural studies.

PMID- 22142397
TI  - Speaking to like-minded individuals.

PMID- 22142398
TI  - Novel phage amplified multichannel series piezoelectric quartz crystal sensor for
      rapid and sensitive detection of Mycobacterium tuberculosis.
AB  - The key factors that control the spread and mortality rate of tuberculosis (TB)
      are rapid detection and diagnosis. However, the current detection of
      Mycobacterium tuberculosis (M. tuberculosis) cannot meet the recommended
      requirements for clinical diagnosis in turnaround time. In this paper, the
      feature of phage D29 that infects M. tuberculosis and Mycobacterium smegmatis (M.
      smegmatis) was combined with the sensitivity of multichannel series piezoelectric
      quartz crystal sensor (MSPQC) to detect M. tuberculosis. The phage D29 played a
      role of inhibiting the growth of M. tuberculosis and M. smegmatis. M.
      tuberculosis is used to protect phage D29 from being killed by ferrous ammonium
      sulfate (FAS) and carries phage D29 into the detection medium containing M.
      smegmatis. The action of M. smegmatis indicated the existence state of phage D29
      in the detection medium. The growth curve of M. smegmatis obtained by MSPQC
      indicated the state of the growth of M. tuberculosis. Therefore, M. tuberculosis
      in the sample could be rapidly detected by evaluating the extent of inhibiting
      the growth of M. smegmatis compared with the normal growth of M. smegmatis. The
      detection of M. tuberculosis was transformed into the detection of M. smegmatis,
      which is more rapid and sensitive than that of M. tuberculosis. For 10(2) cfu/mL
      of M. tuberculosis in clinical sample, the turnaround time was less than 30 h.
      Although statistical analysis showed that no significant difference existed
      between the results of the proposed method here and the BACTEC960 MGIT method in
      clinical M. tuberculosis detection, the phage amplified MSPQC (PA MSPQC) method
      presented here was faster and more economical.

PMID- 22142399
TI  - TMPRSS2-ERG -specific transcriptional modulation is associated with prostate
      cancer biomarkers and TGF-beta signaling.
AB  - BACKGROUND: TMPRSS2-ERG gene fusions occur in about 50% of all prostate cancer
      cases and represent promising markers for molecular subtyping. Although TMPRSS2
      ERG fusion seems to be a critical event in prostate cancer, the precise
      functional role in cancer development and progression is still unclear. METHODS:
      We studied large-scale gene expression profiles in 47 prostate tumor tissue
      samples and in 48 normal prostate tissue samples taken from the non-suspect area
      of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays.
      RESULTS: Comparison of gene expression levels among TMPRSS2-ERG fusion-positive
      and negative tumors as well as benign samples demonstrated a distinct
      transcriptional program induced by the gene fusion event. Well-known biomarkers
      for prostate cancer detection like CRISP3 were found to be associated with the
      gene fusion status. WNT and TGF-beta/BMP signaling pathways were significantly
      associated with genes upregulated in TMPRSS2-ERG fusion-positive tumors.
      CONCLUSIONS: The TMPRSS2-ERG gene fusion results in the modulation of
      transcriptional patterns and cellular pathways with potential consequences for
      prostate cancer progression. Well-known biomarkers for prostate cancer detection
      were found to be associated with the gene fusion. Our results suggest that the
      fusion status should be considered in retrospective and future studies to assess
      biomarkers for prostate cancer detection, progression and targeted therapy.

PMID- 22142400
TI  - Near-real-time combustion monitoring for PCDD/PCDF indicators by GC-REMPI-TOFMS.
AB  - The boiler exit flue gas of a municipal waste combustor was sampled to evaluate
      an online monitoring system for chlorobenzene congeners as indicators of
      polychlorinated dibenzodioxin and dibenzofuran (PCDD/PCDF) concentrations.
      Continuous measurements of chlorobenzene congeners using gas chromatography
      coupled to a resonance-enhanced multiphoton ionization - time-of-flight mass
      spectrometry (GC-REMPI-TOFMS) system were compared over 5-min periods with
      conventional sampling methods for PCDD/PCDF. Three pairs of values were taken
      every hour over a period of three days to characterize the combustor's response
      to transient operating conditions (shutdowns and startups). Isolation of specific
      chlorobenzene congeners from other same-mass compounds was accomplished by using
      a GC column separator ahead of the REMPI-TOFMS. The 50-fold variation of
      PCDD/PCDF concentration was paralleled by similar changes in monitored compounds
      of 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 1,2,3-trichlorobenzene, and
      1,2,4,5-tetrachlorobenzene. A correlation of R = 0.85 and 0.89 was established
      between 40 pairs of simultaneous 5-min GC-REMPI-TOFMS measurements of 1,2,4
      trichlorobenzene and 5 min conventional sampling and analysis for the TEQ and
      Total measures of PCDD/PCDF, respectively. The GC-REMPI-TOFMS system can be used
      to provide frequent measures of correlative PCDD/PCDF concentration thereby
      allowing for an understanding of measures to minimize PCDD/PCDF formation and
      develop operational feedback to limit emissions.

PMID- 22142401
TI  - Systems cancer medicine: towards realization of predictive, preventive,
      personalized and participatory (P4) medicine.
AB  - A grand challenge impeding optimal treatment outcomes for patients with cancer
      arises from the complex nature of the disease: the cellular heterogeneity, the
      myriad of dysfunctional molecular and genetic networks as results of genetic
      (somatic) and environmental perturbations. Systems biology, with its holistic
      approach to understanding fundamental principles in biology, and the empowering
      technologies in genomics, proteomics, single-cell analysis, microfluidics and
      computational strategies, enables a comprehensive approach to medicine, which
      strives to unveil the pathogenic mechanisms of diseases, identify disease
      biomarkers and begin thinking about new strategies for drug target discovery. The
      integration of multidimensional high-throughput 'omics' measurements from tumour
      tissues and corresponding blood specimens, together with new systems strategies
      for diagnostics, enables the identification of cancer biomarkers that will enable
      presymptomatic diagnosis, stratification of disease, assessment of disease
      progression, evaluation of patient response to therapy and the identification of
      reoccurrences. Whilst some aspects of systems medicine are being adopted in
      clinical oncology practice through companion molecular diagnostics for
      personalized therapy, the mounting influx of global quantitative data from both
      wellness and diseases is shaping up a transformational paradigm in medicine we
      termed 'predictive', 'preventive', 'personalized', and 'participatory' (P4)
      medicine, which requires new strategies, both scientific and organizational, to
      enable bringing this revolution in medicine to patients and to the healthcare
      system. P4 medicine will have a profound impact on society - transforming the
      healthcare system, turning around the ever escalating costs of healthcare,
      digitizing the practice of medicine and creating enormous economic opportunities
      for those organizations and nations that embrace this revolution.

PMID- 22142402
TI  - What are the real risks for breast cancer?
AB  - There is a steady drumbeat of peer-reviewed medical articles relating risks of
      breast cancer from a variety of factors. Whether or not the reported factors are
      under the control of any given individual, they have been trumpeted by the lay
      media and are responsible for the understandable finding among women that breast
      cancer generates more anxiety than heart disease, even though the number of US
      women who died of heart disease in 2010 is over seven and a half times the number
      who fell victim to breast cancer. This article attempts to reduce the anxiety
      inducing barrage of these reports by orienting physicians to better understand
      the validity of reported breast cancer risk factors. We hope to provide this
      understanding by: explaining the difference between relative and absolute risk,
      encouraging application of the 95% confidence interval to better evaluate the
      statistical validity of any given risk factor; placing the reported risk factors
      in the context of an accepted risk factor like cigarette smoking and lung cancer;
      and communicating the limits of statistical validity in the absence of
      reproducibility. This review will, to a small degree, provide a balance to the
      reports currently dominating the literature.

PMID- 22142404
TI  - Margin status after laparoscopic radical prostatectomy and the index lesion:
      implications for preoperative evaluation of tumor focality in prostate cancer.
AB  - PURPOSE: The objective of this study was to evaluate the impact of tumor focality
      on positive surgical margins (PSM) after laparoscopic radical prostatectomy.
      PATIENTS AND METHODS: Ninety-five consecutive whole-mount laparoscopic radical
      prostatectomy samples (January 2007 to November 2009) were evaluated for tumor
      focality, laterality, Gleason score, and volume of individual foci, total tumor
      volume, pathologic stage, and surgical margin status. RESULTS: Thirty-nine
      percent, 36%, and 25% were in low, intermediate, and high D'Amico risk
      categories. Thirty-three percent (31/95) had PSM. Overall, 269 tumor foci were
      identified. The incidence of PSM within lesions <= 0.5 cc and <= 0.2 cc was 1.2%
      (2/160) and 0% (0/132), respectively. Among the 71 multifocal cases, 19 (27%)
      exhibited PSM. In 13 of these, the index lesion appeared at the inked surface
      (mean volume 5.4 cc, range 0.63-26.9 cc) compared with 6 in which both index and
      satellite foci appeared at the inked margins. Mean volume of these satellite foci
      was 1.06 cc (range 0.22-2 cc); three had Gleason score 6 and three had Gleason
      score 7 (3+4). CONCLUSIONS: PSM is usually attributed to the index lesion and
      lesions larger than commonly used thresholds for clinically significant lesion
      volumes. Because such lesions might be detected by multiparametric magnetic
      resonance imaging (MRI) or template mapping biopsies, the information from these
      staging modalities could be used intraoperatively to reduce PSM.

PMID- 22142403
TI  - Structural characterization of the caveolin scaffolding domain in association
      with cholesterol-rich membranes.
AB  - Members of the caveolin protein family are implicated in the formation of
      caveolae and play important roles in a number of signaling pathways and in the
      regulation of various proteins. We employ complementary spectroscopic methods to
      study the structure of the caveolin scaffolding domain (CSD) in caveolin-1
      fragments, while bound to cholesterol-rich membranes. This key domain is thought
      to be involved in multiple critical functions that include protein recognition,
      oligomerization, and cholesterol binding. In our membrane-bound peptides,
      residues within the flanking intramembrane domain (IMD) are found to adopt an
      alpha-helical structure, consistent with its commonly believed helical hairpin
      conformation. Intriguingly, in these same peptides, we observe a beta-stranded
      conformation for residues in the CSD, contrasting with earlier reports, which
      commonly do not reflect beta-structure. Our experimental data based on solid
      state NMR, CD, and FTIR are found to be consistent with computational analyses of
      the secondary structure preference of the primary sequence. We discuss how our
      structural data of membrane binding Cav fragments may match certain general
      features of cholesterol-binding domains and could be consistent with the role for
      CSD in protein recognition and homo-oligomerization.

PMID- 22142405
TI  - The response of human ectomesenchymal dental pulp stem cells to cisplatin
      treatment.
AB  - AIM: To determine the response of dental pulp stem cells (DPSCs) to DNA-damaging
      cytostatic cisplatin and compare it with the response of normal human dermal
      fibroblasts (HDFs). METHODOLOGY: Dental pulp stem cells were exposed to 5, 10, 20
      or 40 MUmol L(-1) of cisplatin. The proliferation of affected cells was assessed
      by a Z2 Counter and viability was assessed by means of a Vi-Cell XR using Trypan
      blue exclusion staining. Cell cycle analysis and induction of apoptosis were
      performed by flow cytometry. Induction of apoptosis was determined by monitoring
      the activities of caspases. The expression of proteins was detected by
      electrophoresis and Western blotting. The descriptive statistics of the results
      was analyzed by Student's t-test. RESULTS: Dental pulp stem cells had a greater
      genotoxic stress response to cisplatin compared to HDFs. All three main Mitogen
      activated protein kinases (MAPK) families - extracellular signal-regulated
      kinases (ERK), c-Jun-N-terminal kinase (JNK) and p38 were activated after
      treatment of DPSCs with cisplatin. The activation of MAPK pathways was not
      observed in HDFs exposed to cisplatin. The exposure of DPSCs and HDFs to
      cisplatin provoked an increase in p53 and p21 expression and p53 phosphorylation
      of serine 15. Higher concentrations of cisplatin reduced the viability of DPSCs
      and HDFs and induced the activation of caspases 3/7 and 9. CONCLUSION: Dental
      pulp stem cells had a greater genotoxic stress response to cisplatin compared to
      HDFs. Cisplatin in higher concentrations triggered activation of MAPK and
      apoptosis in DPSCs but not in HDFs.

PMID- 22142406
TI  - Asthma phenotypes: consistency of classification using induced sputum.
AB  - BACKGROUND AND OBJECTIVE: Asthma can be classified as eosinophilic or non
      eosinophilic based on the cell profile of induced sputum. This classification can
      help determine whether corticosteroid treatment is indicated. We assessed the
      stability of these phenotypes over time and with different treatment regimens.
      METHODS: Clinically stable, non-smoking, asthmatic adults were enrolled in one of
      two studies. In study one, induced sputum cell counts from 28 subjects were
      analysed after 4 weeks without corticosteroid treatment and after 6 week
      treatments with placebo, regular inhaled beta-agonist, inhaled corticosteroid,
      and combined beta-agonist and corticosteroid. In study two, sputum from 26
      subjects with non-eosinophilic asthma was analysed after 12 weeks of placebo and
      after four 2-week corticosteroid washouts. Sputum with <2% eosinophils was
      classified as non-eosinophilic. RESULTS: Sputum classification changed frequently
      in both studies. In study one, only one of eight participants with non
      eosinophilic sputum after placebo treatment remained non-eosinophilic throughout.
      In study two, all of participants had at least one eosinophilic sputum sample,
      despite the fact that all had been non-eosinophilic at recruitment. Neutrophilic
      asthma was uncommon in both studies and was also inconsistent. CONCLUSIONS: The
      phenotypic classification of asthma changes frequently. A diagnosis of non
      eosinophilic asthma should not be based on a single sputum sample.

PMID- 22142407
TI  - Asian consensus report on functional dyspepsia.
AB  - BACKGROUND AND AIM: Environmental factors such as food, lifestyle and prevalence
      of Helicobacter pylori infection are widely different in Asian countries compared
      with the West, and physiological functions and genetic factors of Asians may also
      be different from those of Westerners. Establishing an Asian consensus for
      functional dyspepsia is crucial in order to attract attention to such data from
      Asian countries, to articulate the experience and views of Asian experts, and to
      provide a relevant guide on management of functional dyspepsia for primary care
      physicians working in Asia. METHODS: Consensus team members were selected from
      Asian experts and consensus development was carried out by using a modified
      Delphi method. Consensus teams collected published papers on functional dyspepsia
      especially from Asia and developed candidate consensus statements based on the
      generated clinical questions. At the first face-to-face meeting, each statement
      was reviewed and e-mail voting was done twice. At the second face-to-face
      meeting, final voting on each statement was done using a keypad voting system. A
      grade of evidence and strength of recommendation were applied to each statement
      according to the method of the GRADE Working Group. RESULTS: Twenty-nine
      consensus statements were finalized, including seven for definition and
      diagnosis, five for epidemiology, nine for pathophysiology, and eight for
      management. Algorithms for diagnosis and management of functional dyspepsia were
      added. CONCLUSIONS:   This consensus developed by Asian experts shows distinctive
      features of functional dyspepsia in Asia and will provide a guide to the
      diagnosis and management of functional dyspepsia for Asian primary care
      physicians.

PMID- 22142408
TI  - Effect of low-dose amitriptyline on autonomic functions and peripheral blood flow
      in fibromyalgia: a pilot study.
AB  - OBJECTIVE: Amitriptyline (10-50mg) is the most common drug prescribed for the
      treatment of fibromyalgia. Amitriptyline influences the autonomic nervous system,
      as is well known; fibromyalgia is also associated with dysautonomia. The present
      preliminary study was designed to observe the effects of amitriptyline prescribed
      in a low dose (10mg) on the autonomic function tests and blood flow measurements
      in well-diagnosed patients with fibromyalgia. METHODOLOGY: Amitriptyline (10mg)
      was prescribed for 3 months to 21 female patients with fibromyalgia. A standard
      battery of noninvasive autonomic function tests comprising of lying to standing
      test, hand grip test, cold pressor test, deep breathing test, and Valsalva
      maneuver was performed both before and after amitriptyline therapy to study the
      autonomic reactivity of the patients with fibromyalgia. Heart rate variability
      analysis was done to quantify autonomic tone (activity). Blood flow measurement
      around the knee joint was performed using impedance plethysmography technique.
      The patients were also assessed for 10 major clinical symptoms of primary
      fibromyalgia and state and trait anxiety (state and trait anxiety inventory) at
      both instances. RESULTS: No significant changes in autonomic activity (tone) and
      reactivity were observed after amitriptyline therapy. Clinical symptom score and
      anxiety scores (both state and trait) decreased significantly from the
      pretreatment values. Blood flow measurement showed significant improvement in
      blood flow index values at the affected sites after amitriptyline therapy.
      CONCLUSION: Amitriptyline therapy (10mg for 3 months) increases blood flow to the
      affected sites. It does not affect autonomic tone and reactivity in the patients
      with fibromyalgia.

PMID- 22142409
TI  - Bioadhesiveness and efficient mechanotransduction stimuli synergistically
      provided by bacterial inclusion bodies as scaffolds for tissue engineering.
AB  - BACKGROUND: Bacterial inclusion bodies (IBs), mechanically stable, submicron
      protein particles of 50-500 nm dramatically favor mammalian cell spread when used
      for substrate surface decoration. The mechanisms supporting fast colonization of
      IB-modified surfaces have not yet been identified. RESULTS: This study provides
      evidence of mechanotransduction-mediated stimulation of mammalian cell
      proliferation on IB-decorated surfaces, as observed by the enhanced
      phosphorylation of the signal-regulated protein kinase and by the dramatic
      emission of filopodia in the presence of IBs. Interestingly, the results also
      show that IBs are highly bioadhesive materials, and that mammalian cell expansion
      on IBs is synergistically supported by both enhanced adhesion and mechanical
      stimulation of cell division. DISCUSSION: The extent in which these events
      influence cell growth depends on the particular cell line response but it is also
      determined by the genetic background of the IB-producing bacteria, thus opening
      exciting possibilities for the fine tailoring of protein nanoparticle features
      that are relevant in tissue engineering.

PMID- 22142410
TI  - Effects of exercise and amino acid supplementation on body composition and
      physical function in community-dwelling elderly Japanese sarcopenic women: a
      randomized controlled trial.
AB  - OBJECTIVES: To evaluate the effectiveness of exercise and amino acid
      supplementation in enhancing muscle mass and strength in community-dwelling
      elderly sarcopenic women. DESIGN: Randomized controlled trial. SETTING: Urban
      community in Tokyo, Japan. PARTICIPANTS: One hundred fifty-five women aged 75 and
      older were defined as sarcopenic and randomly assigned to one of four groups:
      exercise and amino acid supplementation (exercise + AAS; n = 38), exercise (n =
      39), amino acid supplementation (AAS; n = 39), or health education (HE; n = 39).
      INTERVENTION: The exercise group attended a 60-minute comprehensive training
      program twice a week, and the AAS group ingested 3 g of a leucine-rich essential
      amino acid mixture twice a day for 3 months. MEASUREMENTS: Body composition was
      determined using bioelectrical impedance analysis. Data from interviews and
      functional fitness parameters such as muscle strength and walking ability were
      collected at baseline and after the 3-month intervention. RESULTS: A significant
      group * time interaction was seen in leg muscle mass (P = .007), usual walking
      speed (P = .007), and knee extension strength (P = .017). The within-group
      analysis showed that walking speed significantly increased in all three
      intervention groups, leg muscle mass in the exercise + AAS and exercise groups,
      and knee extension strength only in the exercise + AAS group (9.3% increase, P =
      .01). The odds ratio for leg muscle mass and knee extension strength improvement
      was more than four times as great in the exercise + AAS group (odds ratio = 4.89,
      95% confidence interval = 1.89-11.27) as in the HE group. CONCLUSION: The data
      suggest that exercise and AAS together may be effective in enhancing not only
      muscle strength, but also combined variables of muscle mass and walking speed and
      of muscle mass and strength in sarcopenic women.

PMID- 22142411
TI  - Room-temperature photodetection dynamics of single GaN nanowires.
AB  - We report on the photocurrent behavior of single GaN n-i-n nanowires (NWs) grown
      by plasma-assisted molecular-beam epitaxy on Si(111). These structures present a
      photoconductive gain in the range of 10(5)-10(8) and an ultraviolet (350 nm) to
      visible (450 nm) responsivity ratio larger than 6 orders of magnitude. Polarized
      light couples with the NW geometry with a maximum photoresponse for polarization
      along the NW axis. The photocurrent scales sublinearly with optical power,
      following a I ~ P(beta) law (beta < 1) in the measured range with beta increasing
      with the measuring frequency. The photocurrent time response remains in the
      millisecond range, which is in contrast to the persistent (hours)
      photoconductivity effects observed in two-dimensional photoconductors. The
      photocurrent is independent of the measuring atmosphere, either in the air or in
      vacuum. Results are interpreted taking into account the effect of surface states
      and the total depletion of the NW intrinsic region.

PMID- 22142412
TI  - Implementation of immunohistochemistry on frozen ear notch tissue samples in
      diagnosis of bovine viral diarrhea virus in persistently infected cattle.
AB  - BACKGROUND: Bovine viral diarrhea is a contagious disease of domestic and wild
      ruminants and one of the most economically important diseases in cattle. Bovine
      viral diarrhea virus belongs to the genus Pestivirus, within the family
      Flaviviridae. The identification and elimination of the persistently infected
      animals from herds is the initial step in the control and eradication programs.
      It is therefore necessary to have reliable methods for diagnosis of bovine viral
      diarrhea virus. One of those methods is immunohistochemistry.
      Immunohistochemistry on formalin fixed, paraffin embedded tissue is a routine
      technique in diagnosis of persistently infected cattle from ear notch tissue
      samples. However, such technique is inappropriate due to complicated tissue
      fixation process and it requires more days for preparation. On the contrary,
      immunohistochemistry on frozen tissue was usually applied on organs from dead
      animals. In this paper, for the first time, the imunohistochemistry on frozen ear
      notch tissue samples was described. FINDINGS: Seventeen ear notch tissue samples
      were obtained during the period 2008-2009 from persistently infected cattle.
      Samples were fixed in liquid nitrogen and stored on -20 degrees C until testing.
      Ear notch tissue samples from all persistently infected cattle showed positive
      results with good section quality and possibility to determinate type of infected
      cells. CONCLUSIONS: Although the number of samples was limited, this study
      indicated that immunohistochemistry on formalin fixed paraffin embedded tissue
      can be successfully replaced with immunohistochemistry on frozen ear notch tissue
      samples in diagnosis of persistently infected cattle.

PMID- 22142414
TI  - Synthesis of new ESIPT-fluorescein: photophysics of pH sensitivity and
      fluorescence.
AB  - ESIPT-inspired benzimidazolyl substituted fluorescein dyes were synthesized. PH
      sensitivity was determined by the photophysical property measured at a
      physiological possible pH range. Fluorescence quantum efficiency values were
      calculated independently at two different emissions. A rational relationship is
      defined between fluorescence quantum efficiency and calculated HOMO energy.

PMID- 22142413
TI  - Advanced glycation end products (AGEs) in relation to atherosclerotic lipid
      profiles in middle-aged and elderly diabetic patients.
AB  - OBJECTIVES: To evaluate the association between AGEs and atherosclerotic lipid
      profiles among aging diabetic patients in Taiwan. DESIGN AND METHODS: After age
      and gender matching, we selected 207 diabetic subjects and 174 diabetic subjects
      with proteinuria. Lipid profiles, including total cholesterol (TC), triglycerides
      (TG), high density cholesterol-lipoprotein (HDL-C) and low density lipoprotein
      cholesterol (LDL-C) were measured using standard methods. AGEs were measured with
      the immunoassay method. RESULTS: In general, males were heavier; however, females
      had higher AGEs, fasting glucose (GLU), TC, HDL-C and LDL-C levels than males,
      and had higher TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C ratios compared to males. AGEs
      were more strongly correlated with TG levels and TCL/LDL-C, LDL-C/HDL-C and
      TG/HDL-C ratios when compared to glucose or hemoglobin A1c. Subjects had higher
      AGEs levels (? 2.0 AU) with more adverse lipid profiles. CONCLUSION: AGEs seem to
      be a good biomarker to evaluate the association between diabetes and
      atherosclerotic disorders in aging diabetes.

PMID- 22142416
TI  - Nanopolymeric micelle effect on the transdermal permeability, the bioavailability
      and gene expression of plasmid.
AB  - This study attempts to investigate the transdermal permeability, the
      bioavailability and gene expression of plasmid formulated with nonionic
      poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO)
      polymeric micelles (PM). Dynamic light scattering (DLS) and atomic force
      microscopy (AFM) were used to analyze the PM formulated pCMV-Lac Z (P/PM)
      containing the gene for beta-galactosidase (beta-Gal) driven by cytomegalovirus
      early promoter. Franz diffusion cell was used for in vitro transdermal
      permeability analysis. Real-time PCR was used to quantify the permeated plasmid
      in vitro and in vivo. beta-Gal activity assay was performed to evaluate transgene
      expression in vivo. The size of P/PM was ~50 nm with round shape. PM
      significantly enhanced the in vitro transdermal permeability of plasmid in a
      direction- and temperature-dependent manner. Following transdermal application of
      P/PM, higher area under the curve (AUC(P/PM): 98.34 h.ng/mL) and longer half-life
      of plasmid were detected compared with that of plasmid alone (AUC(P): 10.12
      h.ng/mL). Additionally, the beta-Gal activity was significantly increased in
      skin, stomach, brain and spinal cord at both 48 and 72 h after P/PM application
      and in testis and spleen at 72 h postapplication. In conclusion, PM formulation
      enhanced the permeation of plasmid through skin into blood circulation,
      increasing its absorption and the transgene expression in various tissues.

PMID- 22142417
TI  - Visual and confocal microscopic interpretation of patch tests to benzethonium
      chloride and benzalkonium chloride.
AB  - BACKGROUND: Quaternary ammonium compounds (Quats), such as benzalkonium chloride
      (BAC) and benzethonium chloride (BEC), are widely used as antibacterial active
      ingredients and preservatives in personal care products, disinfectants, and
      ophthalmic preparations. BAC is known to be a marginal irritant when patch tested
      at 0.15% aq. Data on BEC are limited. OBJECTIVE: To differentiate irritant from
      allergic patch test reactions to quaternary ammonium compounds. METHODS: Eight
      subjects who were considered likely to react based on history of rash after
      exposure to disinfectants or a history of prior positive patch test to BAC were
      recruited, as well as two patients undergoing routine patch testing. BAC (0.15%
      aq), BAC (0.15% pet), BEC (0.05% aq), BEC (0.15% pet), BEC (0.15% aq), BEC (0.5%
      aq), sodium lauryl sulfate (2.0%), and deionized water were applied under Finn
      chambers for 48 h. Four days and 7 days after application, the sites were
      examined visually and then by in vivo reflectance confocal microscopy (RCM) which
      was interpreted by blinded experts. RESULTS: Two patients with definite allergic
      reactions according to visual patch test reads and RCM were clinically relevant.
      Cross-reaction between BEC and BAC was demonstrated in one patient. RCM imaging
      correlated well with clinical scoring and interpretation of patch test reactions
      in terms of irritancy vs. allergy for BEC and BAC. CONCLUSION: Relevant allergic
      reactions to quats occur in humans. Possible cross-reaction was noted to occur
      between BAC and BEC. RCM appears to be a useful tool in distinguishing between
      irritancy and sensitization during patch testing to BAC and BEC. Further study of
      prevalence and best test concentration and vehicle is needed.

PMID- 22142418
TI  - First report of high levels of clindamycin-resistant Propionibacterium acnes
      carrying erm(X) in Japanese patients with acne vulgaris.

PMID- 22142419
TI  - Reduced peak oxygen uptake and implications for cardiovascular health and quality
      of life in patients with schizophrenia.
AB  - BACKGROUND: Peak oxygen uptake (VO(2peak)) is a strong predictor of
      cardiovascular disease (CVD) and all-cause mortality, but is inadequately
      described in patients with schizophrenia. The aim of this study was to evaluate
      treadmill VO(2peak), CVD risk factors and quality of life (QOL) in patients with
      schizophrenia (ICD-10, F20-29). METHODS: 33 patients, 22 men (33.7 +/- 10.4
      years) and 11 women (35.9 +/- 11.5 years), were included. Patients VO(2peak) were
      compared with normative VO(2peak) in healthy individuals from the Nord-Trondelag
      Health Study (HUNT). Risk factors were compared above and below the VO(2peak)
      thresholds; 44.2 and 35.1 ml.kg-1.min-1 in men and women, respectively. RESULTS:
      VO(2peak) was 37.1 +/- 9.2 ml.kg-1.min-1 in men with schizophrenia; 74 +/- 19% of
      normative healthy men (p < 0.001). VO(2peak) was 35.6 +/- 10.7 ml.kg-1.min-1 in
      women with schizophrenia; 89 +/- 25% of normative healthy women (n.s.). Based on
      odds ratio patients were 28.3 (95% CI = 1.6-505.6) times more likely to have one
      or more CVD risk factors if they were below the VO(2peak) thresholds. VO(2peak)
      correlated with the SF-36 physical functioning (r = 0.58), general health (r =
      0.53), vitality (r = 0.47), social function (r = 0.41) and physical component
      score (r = 0.51). CONCLUSION: Men with schizophrenia have lower VO(2peak) than
      the general population. Patients with the lowest VO(2peak) have higher odds of
      having one or more risk factors for cardiovascular disease. VO(2peak) should be
      regarded as least as important as the conventional risk factors for CVD and
      evaluation of VO(2peak) should be incorporated in clinical practice.

PMID- 22142420
TI  - Epilepsy in four genetically determined syndromes of intellectual disability.
AB  - BACKGROUND: Epilepsy occurs with increased frequency in people with an
      intellectual disability (ID) compared to the rest of the population. A variety of
      research has in recent years shed light on genetic and biochemical aetiologies of
      epilepsy and, often in a different literature, on syndromes of ID. The aims of
      this annotation are to review developments in understanding of the
      pathophysiology of several ID syndromes in which epilepsy is a frequent co
      occurrence and to relate these observations to recent advances in understanding
      of how these pathophysiological disturbances may lead to epilepsy. METHOD: The ID
      syndromes selected for review were fragile X (FXS), Rett (RTT) and Angelman
      syndromes (AS) and tuberous sclerosis complex (TSC). Epilepsy is a significant
      aspect of these syndromes and relevant research into the genetic and biochemical
      pathophysiology of these four ID syndromes may be informative in establishing the
      association between epilepsy and ID. Employing a structured approach the authors
      initially searched the PubMed database for large case series describing the
      characteristics of epilepsy as manifested in these ID syndromes. The criteria for
      inclusion of the case series in the review were a sample size of greater than 50
      and the description of several of the characteristic features of epilepsy, namely
      prevalence of seizures, age of seizure onset, seizure frequency, seizure
      semiology, severity and treatment. Following this, studies of the genetic and
      biochemical pathophysiology of these four ID syndromes were reviewed and the
      potential relevance of this research in understanding the association with
      epilepsy highlighted. Findings were considered in a focused manner in terms of
      effects on excitatory and inhibitory neurotransmitter systems and on glial
      function. RESULTS: Diverse genetic pathologies underlying several ID syndromes
      can lead to alterations in the functioning of the glutamatergic and GABAergic
      neurotransmitter systems. The mechanisms involved include transcriptional
      regulation in RTT, translational regulation in FXS and TSC, and UBE3A-mediated
      proteolysis in AS. Expression or functioning of receptor subunits, uptake sites
      and enzymes involved in neurotransmitter metabolism are often affected by these
      changes, and may lead to modifications in network excitability and neuronal
      plasticity that may contribute to epileptogenesis and ID. Dysfunction in
      astrocytes may also contribute to epileptogenesis and ID in FXS, RTT and TSC with
      potential mechanisms including failure of astrocytic support functions, glial
      inflammation and homeostatic disturbances that affect the excitability and
      architecture of neuronal networks. CONCLUSIONS: The annotation highlights
      research describing disturbances in excitatory and inhibitory neurotransmitter
      systems, neuronal ion channel and glial functions that provide possible
      explanations for the co-occurrence of seizures within several ID syndromes, in
      some cases suggesting possible avenues for research into novel therapeutic
      targets. Phenotypic overlaps between syndromes may also relate to roles for the
      implicated genes in different disturbances in linked biochemical pathways.

PMID- 22142422
TI  - Polymerase chain reaction-free, sample-to-answer bacterial detection in 30
      minutes with integrated cell lysis.
AB  - An important goal for improved diagnosis and management of infectious disease is
      the development of rapid and accurate technologies for the decentralized
      detection of bacterial pathogens. Most current clinical methods that identify
      bacterial strains require time-consuming culture of the sample or procedures
      involving the polymerase chain reaction. Neither of these approaches has enabled
      testing at the point-of-need because of the requirement for skilled technicians
      and laboratory facilities. Here, we demonstrate the performance of an effective,
      integrated platform for the rapid detection of bacteria that combines a universal
      bacterial lysis approach and a sensitive nanostructured electrochemical
      biosensor. The lysis is rapid, is effective at releasing intercellular RNA from
      bacterial samples, and can be performed in a simple, cost-effective device
      integrated with an analysis chip. The platform was directly challenged with these
      unpurified lysates in buffer and urine. We successfully detected the presence of
      bacteria with high sensitivity and specificity and achieved a sample-to-answer
      turnaround time of 30 min. We have met the clinically relevant detection limit of
      1 cfu/MUL, indicating that uncultured samples can be analyzed. This advance will
      greatly reduce time to successful detection from days to minutes.

PMID- 22142421
TI  - EPR-ENDOR characterization of (17O, 1H, 2H) water in manganese catalase and its
      relevance to the oxygen-evolving complex of photosystem II.
AB  - The synthesis of efficient water-oxidation catalysts demands insight into the
      only known, naturally occurring water-oxidation catalyst, the oxygen-evolving
      complex (OEC) of photosystem II (PSII). Understanding the water oxidation
      mechanism requires knowledge of where and when substrate water binds to the OEC.
      Mn catalase in its Mn(III)-Mn(IV) state is a protein model of the OEC's S(2)
      state. From (17)O-labeled water exchanged into the di-MU-oxo di-Mn(III,IV)
      coordination sphere of Mn catalase, CW Q-band ENDOR spectroscopy revealed two
      distinctly different (17)O signals incorporated in distinctly different time
      regimes. First, a signal appearing after 2 h of (17)O exchange was detected with
      a 13.0 MHz hyperfine coupling. From similarity in the time scale of isotope
      incorporation and in the (17)O MU-oxo hyperfine coupling of the di-MU-oxo di
      Mn(III,IV) bipyridine model (Usov, O. M.; Grigoryants, V. M.; Tagore, R.;
      Brudvig, G. W.; Scholes, C. P. J. Am. Chem. Soc. 2007, 129, 11886-11887), this
      signal was assigned to MU-oxo oxygen. EPR line broadening was obvious from this
      (17)O MU-oxo species. Earlier exchange proceeded on the minute or faster time
      scale into a non-MU-oxo position, from which (17)O ENDOR showed a smaller 3.8 MHz
      hyperfine coupling and possible quadrupole splittings, indicating a terminal
      water of Mn(III). Exchangeable proton/deuteron hyperfine couplings, consistent
      with terminal water ligation to Mn(III), also appeared. Q-band CW ENDOR from the
      S(2) state of the OEC was obtained following multihour (17)O exchange, which
      showed a (17)O hyperfine signal with a 11 MHz hyperfine coupling, tentatively
      assigned as MU-oxo-(17)O by resemblance to the MU-oxo signals from Mn catalase
      and the di-MU-oxo di-Mn(III,IV) bipyridine model.

PMID- 22142424
TI  - The Severe Sexual Sadism Scale: cross-validation and scale properties.
AB  - The Severe Sexual Sadism Scale (SSSS) is a screening device for the file-based
      assessment of forensically relevant sexual sadism. The SSSS consists of 11
      dichotomous (yes/no) items that code behavioral indicators of severe sexual
      sadism within sexual offenses. Based on an Austrian sample of 105 sexual
      offenders, the present study replicated the 1-dimensional scale structure of the
      SSSS, as evidenced by confirmatory factor analysis. More specifically, the scale
      was commensurate with the 1-parameter logistic test model (Rasch model).
      Reliability was estimated to be good. Criterion validity for the clinical
      diagnosis of sexual sadism was good. With a cutoff value of 7 points, sensitivity
      and specificity were estimated at 56% and 90%, respectively.

PMID- 22142423
TI  - Structure-activity relationships of truncated C2- or C8-substituted adenosine
      derivatives as dual acting A2A and A3 adenosine receptor ligands.
AB  - Truncated N(6)-substituted-4'-oxo- and 4'-thioadenosine derivatives with C2 or C8
      substitution were studied as dual acting A(2A) and A(3) adenosine receptor (AR)
      ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross
      coupling reactions were utilized for functionalization of the C2 position of 6
      chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2
      substituent were required for high affinity at the hA(2A)AR, but hydrophobic C8
      substitution abolished binding at the hA(2A)AR. However, most of synthesized
      compounds displayed medium to high binding affinity at the hA(3)AR, regardless of
      C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several
      compounds tended to be full hA(2A)AR agonists. C2 substitution probed
      geometrically through hA(2A)AR docking was important for binding in order of
      hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually
      as hA(2A)AR agonist and hA(3)AR antagonist, which might be useful for treatment
      of asthma or other inflammatory diseases.

PMID- 22142427
TI  - Digital imaging for cytopathology: are we there yet?

PMID- 22142425
TI  - Proportionate responses to life events influence clinicians' judgments of
      psychological abnormality.
AB  - Psychological abnormality is a fundamental concept in the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV-TR; American Psychiatric
      Association, 2000) and in all clinical evaluations. How do practicing clinical
      psychologists use the context of life events to judge the abnormality of a
      person's current behaviors? The appropriate role of life-event context in
      assessment has long been the subject of intense debate and scrutiny among
      clinical theorists, yet relatively little is known about clinicians' own
      judgments in practice. The authors propose a proportionate-response hypothesis,
      such that judgments of abnormality are influenced by whether the behaviors are a
      disproportionate response to past events, rendering them difficult to understand
      or explain. Licensed, practicing clinical psychologists (N = 77) were presented
      with vignettes describing hypothetical people's behaviors (disordered, mildly
      distressed, or unaffected) that had been preceded by either traumatic or mildly
      distressing events. Experts' judgments of abnormality were strongly and
      systematically influenced by the degree of mismatch between the past event and
      current behaviors in strength and valence, such that the greater the mismatch,
      the more abnormal the person seemed. A separate, additional group of clinical
      psychologists (N = 20) further confirmed that the greater the degree of mismatch,
      the greater the perceived difficulty in understanding the patient. These findings
      held true across clinicians of different theoretical orientations and in
      disorders for which these patterns of judgments ran contrary to formal
      recommendations in the DSM-IV-TR (American Psychiatric Association, 2000). The
      rationality of these effects and implications for clinical decision science are
      discussed.

PMID- 22142428
TI  - The danger to cytopathology of over-specialization and its relevance for
      histopathology.

PMID- 22142429
TI  - Enhanced photocatalytic activity of alpha-methylstyrene oligomerization through
      effective metal-to-ligand charge-transfer localization on the bridging ligand.
AB  - A series of Pd complexes containing a visible-light harvesting moiety with
      various combination of substituents (R, X) were synthesized. The variation of the
      substituents resulted in significant change in the electrochemical and
      photophysical properties of the complexes. Additionally, photocatalytic activity
      drastically increased through the introduction of an electron-donating group on R
      and an electron-withdrawing group on X, respectively. The molecular orbital
      analysis based on density functional theory (DFT) calculation suggested that the
      enhancement of the catalytic activity is due to the effective Metal-to-Ligand
      Charge-Transfer (MLCT) localization on the bridging ligand.

PMID- 22142430
TI  - Role of chemical and mechanical stimuli in mediating bone fracture healing.
AB  - Bone is a remarkable living tissue that provides a framework for animal body
      support and motion. However, under excessive loads and deformations, bone is
      prone is to damage through fracture. Furthermore, once the bone is weakened by
      osteoporosis, bone fracture can occur even after only minimal trauma. Various
      techniques have been developed to treat bone fractures. Successful treatment
      outcomes depend on a fundamental understanding of the biochemical and
      biomechanical environments of the fracture site. Various cell types (e.g.
      mesenchymal stem cells, chondrocytes, osteoblasts and osteoclasts) within the
      fracture site tightly control the healing process by responding to the chemical
      and mechanical microenvironment. However, these mechanochemical regulatory
      mechanisms remain poorly understood at the system level owing to the large range
      of variables, such as age, sex and disease-associated material properties of the
      tissue. Computational modelling can play an important role in unravelling this
      complexity by combining mechanochemical interactions, revealing the dominant
      controlling processes and optimizing system behaviour, thereby enabling the
      development and evaluation of treatment strategies for individual patients.

PMID- 22142431
TI  - Delivering alcohol neurotoxicity into nucleus, when clusterin meets BclXL: a
      commentary.
AB  - The study by Kim and colleagues (in press) demonstrated that the expression of
      nuclear isoform of clusterin is induced by ethanol (EtOH) to participate in
      apoptotic cell death of neurons in developing rodent brain. EtOH-induced nuclear
      clusterin interacts with Bcl(XL), thereby liberating proapoptotic Bax. This study
      indicates the proapoptotic role of nuclear clusterin in EtOH-exposed neurons,
      linking specific nuclear events to alcohol neurotoxicity. The study provides
      novel insights into the molecular mechanisms underlying fetal alcohol spectrum
      disorders.

PMID- 22142433
TI  - The communal coping model of catastrophizing: patient-health provider
      interactions.
AB  - OBJECTIVE: The study sought to elucidate and refine the interpersonal,
      communicative dimension of the communal coping model (CCM) of catastrophizing.
      The primary aim was twofold. First, we examined the relations among pain
      intensity, catastrophizing, and pain behaviors as they function within the
      patient-health provider relationship. Second, we investigated the role of
      catastrophizing and pain behaviors in potentially influencing patient
      satisfaction with the provider, provider attitudes, and provider behavior.
      Mediation models were examined. DESIGN: The study was cross-sectional design with
      repeated measures. SETTING:   This study was conducted at a university-based
      family medicine clinic and a private practice rheumatology clinic. Nineteen
      health providers and 49 chronic pain patients receiving treatment in a medical
      setting completed the study. OUTCOME MEASURES:   Patient outcome measures
      included pain intensity, catastrophizing, pain behaviors, and patient
      satisfaction with the provider. Health provider outcome measures were an
      assessment of provider attitudes and length of medical exam. RESULTS: The
      patient's level of catastrophizing entering the medical exam significantly
      predicted the interactive dynamics between the patient and the health provider
      during the exam and patient satisfaction after the exam. The patient's
      perceptions of pain and catastrophic thought processes may be interpersonally
      expressed to health providers via exaggerated pain behaviors. CONCLUSIONS:
      Current findings indicate suggestions for refining the CCM. Results suggest that
      alleviation of catastrophic cognitions may facilitate more effective
      interpersonal communication within the patient-health provider relationship.
      Identification of those factors that improve patient-provider dynamics has
      important implications for the advancement of treatment for chronic pain and
      reducing the costs associated with persistent pain.

PMID- 22142434
TI  - Effect of endoscopic screening at 1-year intervals on the clinicopathologic
      characteristics and treatment of gastric cancer in South Korea.
AB  - BACKGROUND AND AIM: The recommended interval of endoscopic screening for gastric
      cancer (GC) in a general population is 2 years in Korea. However, it has not been
      determined whether endoscopic screening with a shorter interval is beneficial,
      especially for high-risk groups. METHODS: A total of 415 patients with GC were
      categorized according to whether they had (vigilant screening group) or not (non
      vigilant screening group) undergone endoscopic screening within 1 year before
      being diagnosed with GC. Clinicopathologic GC characteristics of the two groups
      were compared. Next, the same analyses were conducted in subgroups of patients
      with high risk for GC including males, current smokers, first-degree relatives of
      GC; and patients with Helicobacter pylori infection, gastric atrophy, or
      intestinal metaplasia (IM). RESULTS: The proportion of vigilant screening
      patients was 36.1%. Early gastric cancer (EGC) was more frequently observed in
      the vigilant screening group than the non-vigilant screening group (62.7% vs
      49.4%, P = 0.009). In the high-risk factor analyses, EGC was more frequently
      detected among patients with severe IM in the vigilant screening group than the
      non-vigilant screening group (66.7% vs 35.5%, P = 0.047). In addition, more
      patients in the vigilant screening group had undergone endoscopic submucosal
      dissection (ESD; 26.7% vs 0%, P = 0.008) and had stage I (84.6% vs 41.7%, P =
      0.012) than in the non-vigilant screening group. CONCLUSIONS: Endoscopic
      screening for GC at 1-year intervals would be beneficial for patients with severe
      IM in South Korea; this method could detect EGC for which the curative modality
      would be ESD.

PMID- 22142436
TI  - The longitudinal BMI pattern and body composition of patients with anorexia
      nervosa who require urgent hospitalization: A case control study.
AB  - BACKGROUND: The prevention of serious physical complications in anorexia nervosa
      (AN) patients is important. The purpose of this study is to clarify which
      physical and social factors are related to the necessity for urgent
      hospitalization of anorexia nervosa (AN) patients in a long-term starvation
      state. We hypothesized that the change of longitudinal BMI, body composition and
      social background would be useful as an index of the necessity for urgent
      hospitalization. METHODS: AN patients were classified into; urgent
      hospitalization, due to disturbance of consciousness or difficulty walking(n =
      17); planned admission (n = 96); and outpatient treatment only groups (n = 136).
      The longitudinal BMI pattern and the clinical features of these groups were
      examined. In the hospitalization groups, comparison was done of body composition
      variation and the social background, including the educational level and advice
      from family members. RESULTS: After adjusting for age and duration of illness,
      the BMI of the urgent hospitalization group was lower than that of the other
      groups at one year before hospitalization (P < 0.01) and decreased more rapidly
      (P < 0.01). Urgent hospitalization was associated with the fat free mass (FFM) (P
      < 0.01). Between the groups, no considerable difference in social factors was
      found. CONCLUSIONS: The longitudinal pattern of BMI and FFM may be useful for
      understanding the severity in AN from the viewpoint of failure of the homeostasis
      system.

PMID- 22142435
TI  - Improving health-related fitness in children: the Fit-4-Fun randomized controlled
      trial study protocol.
AB  - BACKGROUND: Declining levels of physical fitness in children are linked to an
      increased risk of developing poor physical and mental health. Physical activity
      programs for children that involve regular high intensity physical activity,
      along with muscle and bone strengthening activities, have been identified by the
      World Health Organisation as a key strategy to reduce the escalating burden of
      ill health caused by non-communicable diseases. This paper reports the rationale
      and methods for a school-based intervention designed to improve physical fitness
      and physical activity levels of Grades 5 and 6 primary school children.
      METHODS/DESIGN: Fit-4-Fun is an 8-week multi-component school-based health
      related fitness education intervention and will be evaluated using a group
      randomized controlled trial. Primary schools from the Hunter Region in NSW,
      Australia, will be invited to participate in the program in 2011 with a target
      sample size of 128 primary schools children (age 10-13). The Fit-4-Fun program is
      theoretically grounded and will be implemented applying the Health Promoting
      Schools framework. Students will participate in weekly curriculum-based health
      and physical education lessons, daily break-time physical activities during
      recess and lunch, and will complete an 8-week (3 * per week) home activity
      program with their parents and/or family members. A battery of six health-related
      fitness assessments, four days of pedometery-assessed physical activity and a
      questionnaire, will be administered at baseline, immediate post-intervention (2
      months) and at 6-months (from baseline) to determine intervention effects.
      Details of the methodological aspects of recruitment, inclusion criteria,
      randomization, intervention program, assessments, process evaluation and
      statistical analyses are described. DISCUSSION: The Fit-4-Fun program is an
      innovative school-based intervention targeting fitness improvements in primary
      school children. The program will involve a range of evidence-based behaviour
      change strategies to promote and support physical activity of adequate intensity,
      duration and type, needed to improve health-related fitness. TRIAL REGISTRATION
      NO: Australia and New Zealand Clinical Trials Register (ANZCTR):
      ACTRN12611000976987.

PMID- 22142437
TI  - House cat scratch-induced linear vitiligo as Kobner phenomena.

PMID- 22142438
TI  - Multicomponent synthetic polymers with viral-mimetic chemistry for nucleic acid
      delivery.
AB  - The ability to deliver genetic material for therapy remains an unsolved challenge
      in medicine. Natural gene carriers, such as viruses, have evolved sophisticated
      mechanisms and modular biopolymer architectures to overcome these hurdles. Here
      we describe synthetic multicomponent materials for gene delivery, designed with
      features that mimic virus modular components and which transfect specific cell
      lines with high efficacy. The hierarchical nature of the synthetic carriers
      allows the incorporation of membrane-disrupting peptides, nucleic acid binding
      components, a protective coat layer, and an outer targeting ligand all in a
      single nanoparticle, but with functionality such that each is utilized in a
      specific sequence during the gene delivery process. The experimentally facile
      assembly suggests these materials could form a generic class of carrier systems
      that could be customized for many different therapeutic settings.

PMID- 22142439
TI  - Shape-controlled Au particles for InAs nanowire growth.
AB  - We present a study of InAs nanowire (NW) growth with shape-controlled Au seed
      particles. In comparison to more conventional spherical particles, the highly
      faceted, shaped Au particles are found to enhance the initial growth kinetics of
      InAs NWs at identical growth conditions. Analysis of the NWs after growth by
      transmission electron microscopy and energy-dispersive spectroscopy suggests that
      while In diffuses into the bulk of the shaped Au particles, in accordance with
      the vapor-liquid-solid (VLS) growth mechanism, the surface faceting is preserved.
      A key difference is that the shaped Au particles are characterized by a thicker
      In shell on their surfaces than the spherical Au particles, indicating that
      increased adsorption of In leads to the observed growth rate enhancement. On the
      basis of these results, we propose that our picture of VLS growth in regards to
      liquefaction and droplet formation is incomplete and that the initial particle
      morphology can be used to tailor NW growth.

PMID- 22142440
TI  - Screening for lung cancer: is this the way forward?
AB  - While low-dose CT scans have been shown to detect greater numbers of early lung
      cancers than conventional CXR, the first randomized trial of CT versus CXR
      screening in more than 50 000 subjects has shown a 20% reduction in mortality
      with CT. There are several other randomized trials in progress. CT scanning may
      be a useful technique for identifying lung cancer at an earlier stage and may
      reduce mortality. However, before it can be used on a wider scale, issues such as
      overdiagnosis bias, cost-effectiveness, false positive findings of multiple
      noncalcified nodules and the willingness of the relevant population to accept CT
      scanning need to be evaluated. There is still very little information on the cost
      per life-year saved as a result of CT scanning, as the data to date is very
      imprecise. There is no evidence that screening programs influence smoking rates
      despite the inclusion of cessation programs in many trials. Furthermore, if CT
      screening is adopted, much work is needed to persuade individuals at high risk,
      mostly current or former heavy smokers with some airflow obstruction, to
      participate in a screening program.

PMID- 22142441
TI  - David Grahame Grahame-Smith: clinical pharmacologist. 1933-2011.

PMID- 22142442
TI  - Caregiver and adult patient perspectives on the importance of a diagnosis of
      22q11.2 deletion syndrome.
AB  - BACKGROUND: Recent advances in genetics are particularly relevant in the field of
      intellectual disability (ID), where sub-microscopic deletions or duplications of
      genetic material are increasingly implicated as known or suspected causal
      factors. Data-driven reports on the impact of providing an aetiological
      explanation in ID are needed to help justify widespread use of new and expensive
      genetic technologies. METHODS: We conducted a survey of caregivers on the value
      of a genetic/aetiologic diagnosis of 22q11.2 deletion syndrome (22q11.2DS), the
      most common microdeletion syndrome in ID. We also surveyed the opinion of a high
      functioning subset of adults with 22q11.2DS themselves. We used standard
      quantitative and qualitative methods to analyse the responses. RESULTS: In total,
      73 of 118 surveys were returned (61.9%). There was convergence of quantitative
      and qualitative results, and consistency between adult patient and caregiver
      responses. A definitive molecular diagnosis of 22q11.2DS was a critical event
      with diverse positive repercussions, even if occurring later in life. Frequently
      cited benefits included greater understanding and certainty, newfound sense of
      purpose and a platform for advocacy, and increased opportunities to optimise
      medical, social and educational needs. CONCLUSIONS: This is the first study to
      characterise the impact of a diagnosis of this representative microdeletion
      syndrome on adult patients and their families. The results both validate and
      expand on the theoretical benefits proposed by clinicians and researchers. The
      use of genome-wide microarray technologies will provide an increasing number of
      molecular diagnoses. The importance of a diagnosis of 22q11.2DS demonstrated here
      therefore has implications for changing attitudes about molecular genetic
      diagnosis that could benefit individuals with ID of currently unknown cause and
      their families.

PMID- 22142443
TI  - Oligomer formation of the bacterial second messenger c-di-GMP: reaction rates and
      equilibrium constants indicate a monomeric state at physiological concentrations.
AB  - Cyclic diguanosine-monophosphate (c-di-GMP) is a bacterial signaling molecule
      that triggers a switch from motile to sessile bacterial lifestyles. This
      mechanism is of considerable pharmaceutical interest, since it is related to
      bacterial virulence, biofilm formation, and persistence of infection. Previously,
      c-di-GMP has been reported to display a rich polymorphism of various oligomeric
      forms at millimolar concentrations, which differ in base stacking and G-quartet
      interactions. Here, we have analyzed the equilibrium and exchange kinetics
      between these various forms by NMR spectroscopy. We find that the association of
      the monomer into a dimeric form is in fast exchange (<milliseconds) with an
      equilibrium constant of about 1 mM. At concentrations above 100 MUM, higher
      oligomers are formed in the presence of cations. These are presumably tetramers
      and octamers, with octamers dominating above about 0.5 mM. Thus, at the low
      micromolar concentrations of the cellular environment and in the absence of
      additional compounds that stabilize oligomers, c-di-GMP should be predominantly
      monomeric. This finding has important implications for the understanding of c-di
      GMP recognition by protein receptors. In contrast to the monomer/dimer exchange,
      formation and dissociation of higher oligomers occurs on a time scale of several
      hours to days. The time course can be described quantitatively by a simple
      kinetic model where tetramers are intermediates of octamer formation. The
      extremely slow oligomer dissociation may generate severe artifacts in biological
      experiments when c-di-GMP is diluted from concentrated stock solution. We present
      a simple method to quantify c-di-GMP monomers and oligomers from UV spectra and a
      procedure to dissolve the unwanted oligomers by an annealing step.

PMID- 22142445
TI  - Childbearing differences among three generations of U.S. women.
AB  - Each year a generation of women is born who will share similar sociohistorical
      experiences before and throughout their reproductive lives. These unique
      experiences can produce similar childbearing patterns in terms of the average
      number of children ever born--whether mothers are younger or older when their
      first birth occurs and the proportion of women who do not have children--that can
      differ from the patterns found for other cohorts. Childbearing patterns have
      profound consequences for society. These consequences include the demand for
      schools and housing, as well as women's participation in the labor force.
      Moreover, the lives of women who become mothers are significantly different from
      those who do not. Having children affects the acquisition of material goods and
      may impose costs for the mother in terms of personal and professional options.
      This report presents data on three selected birth cohorts of women representing
      generations born at 25-year intervals in 1910, 1935, and 1960, close to the
      average length of a generation in the United States. Data are from the cohort
      fertility tables, based on the National Vital Statistics System.

PMID- 22142444
TI  - Lycopene inhibits angiogenesis in human umbilical vein endothelial cells and rat
      aortic rings.
AB  - Angiogenesis is important for tumour vascularisation and growth, and is therefore
      a promising target for cancer therapy. The present study reports inhibition of in
      vitro angiogenesis in human umbilical vein endothelial cells (HUVEC) as well as
      in rat aortic rings at physiological concentrations of lycopene, that is, 1-2
      MUmol/l. At a final concentration of 1.15 MUmol/l, a significant reduction (P <
      0.05) in network branching, that is, junction numbers, the number of tubules and
      tubule length, was observed in both HUVEC as well as in the rat aortic rings. The
      inhibitory effect of lycopene was independent of the presence of the pro
      angiogenic agents, vascular endothelial growth factor and TNF-alpha. The anti
      angiogenic effects of lycopene in the present study were shown at a concentration
      that should be achievable by dietary means. These results extend our knowledge of
      one of the putative anti-cancer actions of lycopene.

PMID- 22142446
TI  - Gender differences in facial skin dielectric constant measured at 300 MHz.
AB  - BACKGROUND/PURPOSE: Skin tissue dielectric constant (TDC) measurements at 300 MHz
      provide non-invasive data on free and bound tissue water. TDC-data is available
      for some body sites, but most is for female forearm. Contrastingly, there are no
      data on face-skin or comparative data between genders. Our goals were to obtain
      facial-TDC reference values and determine if TDC-values differ between genders.
      METHODS: TDC was measured at forehead, cheek, and forearm in 60 young adults (30
      men) to a 1.5-mm depth. Measured TDC-values were compared with TDC-values
      calculated using skin-thickness data. RESULTS: Measured TDC-values ranged from
      39.6 +/- 2.9 at male-forehead to 28.2 +/- 2.4 at female forearm and were
      significantly different (P < 0.001) among each site in the order forehead > cheek
      >forearm. Male TDC-values were greater than female TDC-values (P < 0.01) with
      differences from 5.6% at forehead to 11.3% at forearm. Calculated TDC-values
      incorporating site and gender skin-thickness differences yielded TDC-values at
      the most 3% different from measured values. CONCLUSION: Gender differences should
      be considered in clinical studies in which men and women are included in a common
      study population with respect to experimental design and data interpretation.
      This is especially true if absolute TDC-values are of interest rather than
      changes in TDC-values on the same subject subsequent secondary to an
      intervention.

PMID- 22142447
TI  - Challenges in comparing the quality of life of older people between ethnic
      groups, and the implications for national well-being indicators: a secondary
      analysis of two cross-sectional surveys.
AB  - BACKGROUND: The current international interest in well-being indicators among
      governmental agencies means that many quality of life scales are potential
      components of such national indicator sets. Measuring well-being in minority
      groups is complex and challenging. Scales are available that have been validated
      in specific parts of the population, such as older people. However, validation
      among combinations of minority groups, such as older adults of ethnic minority
      backgrounds, is lacking. FINDINGS: We pooled data from two surveys of older
      adults in Great Britain: one conducted among White British people, and one among
      four ethnic minority groups. Quality of life was measured by the Older People's
      Quality of Life (OPQOL); Control, Autonomy, Self-realisation, Pleasure (CASP-19);
      and World Health Organization Quality of Life scale for older people (WHOQOL
      OLD). We found differences, some significant, between groups in terms of self
      reported importance of various aspects of quality of life. A regression model of
      each total quality of life scale revealed greater unexplained variability in the
      White British group than the others. Principal components analysis within each
      ethnic group's data showed considerable differences in the correlation
      structures. CONCLUSIONS: There are differences between ethnic groups that are
      consistent across the three scales and are not explained by a battery of
      predictor variables. If scales such as these are used to compare quality of life
      between ethnic groups, or equivalently between geographical regions, the
      different results in each group are liable to bias any comparison which could
      lead to inequitable policy decisions.

PMID- 22142449
TI  - Risk factors for perforation and delayed bleeding associated with endoscopic
      submucosal dissection for early gastric neoplasms: analysis of 1123 lesions.
AB  - BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is a useful procedure
      for the treatment of early gastric neoplasms; however, this advanced technique
      has also resulted in an increase in serious complications such as perforation and
      delayed bleeding. This study aimed to elucidate the risk factors for these
      complications. METHODS: A total of 1123 lesions diagnosed with early gastric
      neoplasms and treated by ESD at three institutions were investigated.
      Retrospectively, patients with or without these complications were compared on
      the basis of the patient characteristics and treatment results. RESULTS:
      Perforation occurred in 27 lesions (2.4%) and delayed bleeding in 56 lesions
      (5.0%). Multivariate analysis indicated that lesions located in the upper area of
      the stomach (odds ratio [OR]: 4.88, 95% confidence interval [CI]: 2.21-10.75) was
      associated with a significantly higher risk of perforation, and that age >= 80
      years (OR: 2.15, 95% CI: 1.18-3.90) and a long procedure time (OR: 1.01, 95% CI:
      1.001-1.007) were associated with a significantly higher risk of delayed bleeding
      after ESD. The en bloc resection rate (74% vs 94%) and curative resection rate
      (48% vs 85%) of lesions with perforation were significantly lower than those
      without perforation. The rate of residual disease or recurrence after ESD was
      significantly higher in lesions with delayed bleeding than that without delayed
      bleeding (5.4% vs 0.84%). CONCLUSIONS: This study demonstrated risk factors for
      perforation and delayed bleeding associated with ESD. Furthermore, it was
      clarified that perforation and delayed bleeding influenced post-procedure results
      and prognosis after ESD.

PMID- 22142450
TI  - Advancing a national agenda to eliminate disparities in pain care: directions for
      health policy, education, practice, and research.
AB  - BACKGROUND: Pain is strongly associated with significant personal and societal
      costs. A crucial element of any initiative on pain must focus on eliminating pain
      care disparities that are pervasive throughout the United States health care
      settings. OBJECTIVES: This report focuses on macro-level factors related to pain
      care disparities in the United States that may be amenable to policy
      interventions. METHODS: We identify concrete opportunities for achieving equity
      in pain care, especially those occasioned by recent legislative changes in the
      United States health care system. An aggressive policy, advocacy, and research
      agenda is synthesized in five domains: 1) structural/system; 2) policy and
      advocacy; 3) workforce; 4) provider; and 5) research. RESULTS: Inequities in pain
      care remain an important and neglected health policy concern. Many direct and
      indirect provisions within the Affordable Care Act (ACA) and other national
      initiatives that leverage on ACA offer opportunities to achieve equity in pain
      care. These include changes in insurance, in public, provider, and legislative
      education, in primary care and pain specialist training, improving workforce
      diversity, achieving uniformity in race/ethnicity data collection, emphasizing
      patient-centered outcomes research, and encouraging focus on pain care
      disparities within the comparative effectiveness research paradigm. CONCLUSIONS:
      Recent national legislative initiatives within ACA are expected to generate
      multilevel efforts that will impact the flow of funding to address the pervasive
      issue of disparities. It is an opportune time for the pain community to take a
      lead in implementing a concerted agenda on pain care disparities in order to
      leverage these national initiatives.

PMID- 22142451
TI  - Demonstration of Treponema pallidum by immunohistochemistry in a patient with
      secondary syphilis mimicking pityriasis lichenoides chronica.

PMID- 22142452
TI  - Kinetic and spectroscopic probes of motions and catalysis in the cytochrome P450
      reductase family of enzymes.
AB  - There is a mounting body of evidence to suggest that enzyme motions are linked to
      function, although the design of informative experiments aiming to evaluate how
      this motion facilitates reaction chemistry is challenging. For the family of
      diflavin reductase enzymes, typified by cytochrome P450 reductase, accumulating
      evidence suggests that electron transfer is somehow coupled to large-scale
      conformational change and that protein motions gate the electron transfer
      chemistry. These ideas have emerged from a variety of experimental approaches,
      including structural biology methods (i.e. X-ray crystallography, electron
      paramagnetic/NMR spectroscopies and solution X-ray scattering) and advanced
      spectroscopic techniques that have employed the use of variable pressure kinetic
      methodologies, together with solvent perturbation studies (i.e. ionic strength,
      deuteration and viscosity). Here, we offer a personal perspective on the
      importance of motions to electron transfer in the cytochrome P450 reductase
      family of enzymes, drawing on the detailed insight that can be obtained by
      combining these multiple structural and biophysical approaches.

PMID- 22142453
TI  - Synthesis and photo-physical properties of fluorescent 1,3,5-triazine styryl
      derivatives.
AB  - BACKGROUND: Organic fluorophore contains well-defined D-pi-A (Donor-pi system
      Acceptor) push-pull system have wide application in the field of NLO, OLED and
      high tech application. Electron donor diphenyl, triphenyl and carbazole
      conjugated with electron acceptor terminal through pi-system were reported
      recently for high-tech applications. N,N-Dialkyl substituted 1,3,5-triazine also
      acts as donor keeping this idea in mind we developed D-pi-A styryl dyes. RESULTS:
      Novel "Y"-shaped acceptor-pi-donor-pi-acceptor type of compounds were synthesized
      from 4,4'-((6-(4-(diethylamino)phenyl)-1,3,5-triazine-2,4diyl)bis(oxy))
      dibenzaldehyde (DIPOD) as electron donors and different active methylene
      compounds as electron acceptors by conventional Knoevenagel condensation
      reaction. Their photophysical and thermal properties were investigated.
      CONCLUSION: It was found that the strong electron acceptor-donor chromophoric
      system of these compounds showed high Stoke's shift and excellent thermal
      stability. Compounds showed positive solvatofluorism behavior from nonpolar to
      polar solvent. All compounds have good thermal stability.

PMID- 22142454
TI  - Association between soft drink consumption and asthma and chronic obstructive
      pulmonary disease among adults in Australia.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to examine the association
      between soft drink consumption and self-reported doctor-diagnosed asthma and COPD
      among adults living in South Australia. METHODS: Data were collected using a risk
      factor surveillance system. Each month a representative random sample of South
      Australians were selected from the electronic White Pages and interviews were
      conducted using computer-assisted telephone interviewing (CATI). RESULTS: Among
      16 907 participants aged 16 years and older, 11.4% reported daily soft drink
      consumption of more than half a litre. High levels of soft drink consumption were
      positively associated with asthma and COPD. Overall, 13.3% of participants with
      asthma and 15.6% of those with COPD reported consuming more than half a litre of
      soft drink per day. By multivariate analysis, after adjusting for socio
      demographic and lifestyle factors, the odds ratio (OR) for asthma was 1.26 (95%
      confidence interval (CI): 1.01-1.58) and the OR for COPD was 1.79 (95% CI: 1.32
      2.43), comparing those who consumed more than half a litre of soft drink per day
      with those who did not consume soft drinks. CONCLUSIONS: There was a positive
      association between consumption of soft drinks and asthma/COPD among adults
      living in South Australia.

PMID- 22142455
TI  - Phase selection enabled formation of abrupt axial heterojunctions in branched
      oxide nanowires.
AB  - Rational synthesis of nanowires via the vapor-liquid-solid (VLS) mechanism with
      compositional and structural controls is vitally important for fabricating
      functional nanodevices from bottom up. Here, we show that branched indium tin
      oxide nanowires can be in situ seeded in vapor transport growth using tailored Au
      Cu alloys as catalyst. Furthermore, we demonstrate that VLS synthesis gives
      unprecedented freedom to navigate the ternary In-Sn-O phase diagram, and a rare
      and bulk-unstable cubic phase can be selectively stabilized in nanowires. The
      stabilized cubic fluorite phase possesses an unusual almost equimolar
      concentration of In and Sn, forming a defect-free epitaxial interface with the
      conventional bixbyite phase of tin-doped indium oxide that is the most employed
      transparent conducting oxide. This rational methodology of selecting phases and
      making abrupt axial heterojunctions in nanowires presents advantages over the
      conventional synthesis routes, promising novel composition-modulated
      nanomaterials.

PMID- 22142456
TI  - Learning Disability Liaison Nursing Services in south-east Scotland: a mixed
      methods impact and outcome study.
AB  - BACKGROUND: There have been significant concerns about the care and treatment of
      people with intellectual disabilities (ID) when attending general hospitals,
      which have led to inquiries that highlight service and systems failures. One
      response has been the development of Learning Disability Liaison Nursing (LDLN)
      Services across the UK that aim to ensure that additional, specialist support is
      available for patients, their carers and general healthcare professionals.
      METHODS: A mixed-methods study to investigate the impact of LDLN Services across
      four Scottish NHS boards was undertaken. In total, 323 referrals made over 18
      months were analysed along with qualitative data drawn from interviews and focus
      groups with a sample of 85 participants including patients with ID (n = 5),
      carers (n = 16), primary care healthcare professionals (n = 39) and general
      hospital professionals (n = 19) and learning disability liaison nurses (n = 6).
      RESULTS: The referral patterns to the four liaison nursing services closely
      matched the known health needs of adults with ID, with common admissions being
      due to neurological, respiratory and gastrointestinal issues. The LDLN role was
      seen to be complex and impacted on three key areas: (i) clinical patient care;
      (ii) education and practice development; and (iii) strategic organisational
      developments. Specific patient outcomes were linked to issues relating to
      capacity and consent to treatment, fostering person-centred adjustments to care,
      augmenting communication and the liaison nurses acting as positive role models
      and ambassadors for people with ID. CONCLUSIONS: The LDLN Services were valued by
      stakeholders by achieving person-centred outcomes. With their expert knowledge
      and skills, the liaison nurses had an important role in developing effective
      systems and processes within general hospital settings. The outcomes highlight
      the importance of supporting and promoting LDLN Services and the challenges in
      delivering the multifaceted elements of the role. There is a need to take account
      of the complex and multidimensional nature of the LDLN role and the possible
      tensions between achieving clinical outcomes, education and practice developments
      and organisational strategic initiatives.

PMID- 22142458
TI  - Moderate alcohol consumption alters both leucocyte gene expression profiles and
      circulating proteins related to immune response and lipid metabolism in men.
AB  - Moderate alcohol consumption has various effects on immune and inflammatory
      processes, which could accumulatively modulate chronic disease risk. So far, no
      comprehensive, integrative profiling has been performed to investigate the
      effects of longer-term alcohol consumption. Therefore, we studied the effects of
      alcohol consumption on gene expression patterns using large-scale profiling of
      whole-genome transcriptomics in blood cells and on a number of proteins in blood.
      In a randomised, open-label, cross-over trial, twenty-four young, normal-weight
      men consumed 100 ml vodka (30 g alcohol) with 200 ml orange juice or only orange
      juice daily during dinner for 4 weeks. After each period, blood was sampled for
      measuring gene expression and selected proteins. Pathway analysis of 345 down
      regulated and 455 up-regulated genes revealed effects of alcohol consumption on
      various signalling responses, immune processes and lipid metabolism. Among the
      signalling processes, the most prominently changed was glucocorticoid receptor
      signalling. A network on immune response showed a down-regulated NF-kappaB gene
      expression together with increased plasma adiponectin and decreased pro
      inflammatory IL-1 receptor antagonist and IL-18, and acute-phase proteins
      ferritin and alpha1-antitrypsin concentrations (all P < 0.05) after alcohol
      consumption. Furthermore, a network of gene expression changes related to lipid
      metabolism was observed, with a central role for PPARalpha which was supported by
      increased HDL-cholesterol and several apo concentrations (all P < 0.05) after
      alcohol consumption. In conclusion, an integrated approach of profiling both
      genes and proteins in blood showed that 4 weeks of moderate alcohol consumption
      altered immune responses and lipid metabolism.

PMID- 22142457
TI  - Burden of testicular, paratesticular and extragonadal germ cell tumours in
      Europe.
AB  - We provide updated estimates of survival, incidence, complete prevalence, and
      proportion cured for patients with testicular/paratesticular and extragonadal
      germ cell cancers in Europe, grouped according to the new list of cancer types
      developed by RARECARE. We collected data, archived in European cancer registries,
      with vital status information available to 31st December 2003. We analysed 26,000
      cases of testicular, paratesticular and extragonadal germ cell cancers diagnosed
      1995-2002, estimating that about 15,600 new testicular/paratesticular and 630 new
      extragonadal cancer cases occurred per year in EU27, with annual incidence rates
      of 31.5/1,000,000 and 1.27/1,000,000, respectively. Slightly more than 436,000
      persons were alive at the beginning of 2008 with a diagnosis of
      testicular/paratesticular cancer, and about 17,000 with a diagnosis of
      extragonadal germ cell cancer. Five-year relative survival was 96% for
      testicular/paratesticular cancer and 71% for extragonadal germ cell cancer; the
      proportions cured were 95% and 69%, respectively. We found limited variation in
      survival between European regions except for non-seminomatous testicular cancer,
      for which five-year relative survival ranged from 86% in Eastern Europe to 96% in
      Northern Europe. Survival for all cancer types considered decreased with
      increasing age at diagnosis. Further investigation is required to establish the
      real reasons for the lower survival in Eastern Europe. Considering the high
      prevalence of these highly curable cancers, it is important to monitor patients
      long-term, so as to quantify treatment-related risks and develop treatments
      having limited impact on quality of life.

PMID- 22142459
TI  - Long-term results of breast conservation and immediate volume replacement with
      myocutaneous latissimus dorsi flap.
AB  - BACKGROUND: Published long-term outcomes of oncoplastic breast-conserving surgery
      are scarce and, specifically, aesthetic outcomes assessed with an objective
      method have not previously been published. METHODS: A cohort of 41 patients
      treated with a quadrantectomny and immediate reconstruction using a myocutaneous
      latissimus dorsi flap were analyzed and their aesthetic outcomes were evaluated
      objectively by BCCT.core software. RESULTS: At the end of a 58-month follow-up
      from the date of initial diagnosis, one patient (2.4%) developed an ipsilateral
      recurrence, six patients developed distant metastases and three patients died
      (7.3%) without ipsilateral recurrence, one of them presenting hepatic metastases
      at the time of the initial diagnosis. We were able to evaluate aesthetic results
      in 23 patients, 3 assessed as excellent, 12 good and 8 fair. CONCLUSION: This
      oncoplastic volume replacement technique obtained a good local control and
      satisfactory and stable aesthetic results which have maintained unchanged after a
      long period of time.

PMID- 22142460
TI  - Alopecia areata triggered or exacerbated by swine flu virus infection.

PMID- 22142461
TI  - Prevalence of the JAK2V617F mutation in Chinese patients with Budd-Chiari
      syndrome and portal vein thrombosis: a prospective study.
AB  - BACKGROUND AND AIM: Whether routine screening for the JAK2V617F mutation should
      be performed in Chinese patients with Budd-Chiari syndrome (BCS) and portal vein
      thrombosis (PVT) is unclear. Therefore, we aimed to evaluate the prevalence of
      the JAK2V617F mutation in such patients and to explore the risk factors
      associated with the mutation. METHODS: All consecutive patients with BCS and PVT
      diagnosed between September 2009 and May 2011 were prospectively enrolled in the
      observational study and underwent the JAK2V617F mutation detection. RESULTS:
      Prevalence of the JAK2V617F mutation was 4.3% (4/92) in patients with primary
      BCS, 26.6% (17/64) in non-malignant and non-cirrhotic patients with PVT, and 1.4%
      (1/71) in cirrhotic patients with PVT. All BCS patients with the JAK2V617F
      mutation had both platelet count (PLT) of above 100 * 10(9) /L (range, 107-188 *
      10(9) /L) and splenomegaly. In non-malignant and non-cirrhotic patients with PVT,
      higher PLT and older ages were the independent predictors of the JAK2V617F
      mutation. Further, the difference in PLT between the patients with and without
      the mutation displayed greater significance in the subgroup of patients with
      splenomegaly (P < 0.0001), but the statistical significance disappeared in the
      subgroup of patients with splenectomy (P = 0.1312). CONCLUSIONS: The low
      prevalence of the JAK2V617F mutation in patients with BCS suggests that
      myeloproliferative neoplasm should be an uncommon etiological factor of BCS in
      China. Routine screening for the JAK2V617F mutation might be recommended in non
      malignant and non-cirrhotic patients with PVT, but not in cirrhotic patients with
      PVT. The coexistence of higher PLT and splenomegaly might be closely associated
      with the JAK2V617F mutation.

PMID- 22142462
TI  - Localization of acidic phospholipid cardiolipin and DnaA in mycobacteria.
AB  - Acidic phospholipids such as cardiolipin (CL) have been shown to modulate
      Mycobacterium tuberculosis (Mtb) DnaA interactions with ATP. In the present
      study, using nonyl acridine orange fluorescent dye we localized CL-enriched
      regions to midcell septa and poles of actively dividing cells. We also found that
      CL-enriched regions were not visualized in cells defective for septa formation as
      a consequence of altered FtsZ levels. Using Mtb cultures synchronized for DNA
      replication we show that CL localization could be used as a marker for cell
      division and cell cycle progression. Finally, we show that the localization
      pattern of the DnaA-green fluorescent fusion protein is similar to CL. Our
      results suggest that DnaA colocalizes with CL during cell cycle progression.

PMID- 22142464
TI  - A case of large bladder hemangioma successfully treated with endoscopic yttrium
      aluminium garnet laser irradiation.
AB  - Bladder hemangioma is a rare benign tumor. While partial cystectomy remains an
      effective treatment option for large bladder hemangioma, the combined method of
      neodymium:yttrium aluminium garnet and holmium:yttrium aluminium garnet laser
      irradiation is an effective and less invasive treatment option. We report a case
      of large bladder hemangioma in an otherwise healthy 4-year-old boy, successfully
      treated with serial endoscopic yttrium aluminium garnet laser irradiation. There
      was no recurrence, and normal bladder function was preserved. Serial yttrium
      aluminium garnet laser irradiation is thus a useful, less invasive method for
      cases of large tumors.

PMID- 22142465
TI  - Editorial comment to Reassessment of the UICC revision of T3 renal cell
      carcinomas in a Japanese institute.

PMID- 22142466
TI  - Oncological outcomes of the prostate cancer patients registered in 2004: report
      from the Cancer Registration Committee of the JUA.
AB  - OBJECTIVES: In 2001, the Cancer Registration Committee of the Japanese Urological
      Association initiated a data collection of prostate cancer patients into a
      computer-based database. The aim of the present study is to report the clinical
      and pathological characteristics and outcomes of prostate cancer patients
      diagnosed in 2004 in Japan. METHODS: Overall, 11,385 patients from 239
      institutions were registered into the database. After excluding 1105 patients
      because of insufficient data, duplication or insufficient follow up, 10,280
      patients were eligible for the analysis. Most of them (10,198, 99.2%) were
      Japanese and 1195 (11.6%) had metastatic disease at the time of diagnosis. The
      mean and median follow up was 53.2 months and 61.5 months, respectively. RESULTS:
      The 5-year overall and prostate cancer-specific survival rate was 89.7% and
      94.8%, respectively. The 5-year prostate cancer-specific survival rate of M0 and
      M1 disease was 98.4% and 61.1%, respectively. For 8424 cases of organ-confined or
      regional disease, Japanese urologists used as the initial treatment hormone
      ablation therapy alone (3360, 39.9%), radical prostatectomy (3140, 38.1%),
      radiation therapy (1530, 18.2%) and watchful waiting (394, 4.7%) including active
      surveillance or palliative observation. CONCLUSIONS: This is the first large
      population report of survival data in Japanese prostate cancer patients. In
      Japan, the disease population, survival period with metastatic disease and ratio
      of patients having hormone ablation therapy differ from those in Western
      countries.

PMID- 22142468
TI  - Symmetry distortion in the human hemoglobin tetramer induced by asymmetric
      ligation.
AB  - To investigate the conformational changes in human tetrameric (alphabeta)(2)
      hemoglobin upon binding of the first two ligands, we have measured the kinetics
      of reactions between 4,4'-dithiodipyridine and beta93Cys sulfhydryl groups of
      four diliganded hemoglobins by using CO-bound Fe(II)-Ni(II) hybrids with and
      without beta-beta cross-linking. The data show that all the diliganded
      intermediates have high sulfhydryl reactivities, which are greater than or equal
      to that for the fully-liganded end state, especially when containing liganded
      alpha subunit(s). The results also reveal that both the asymmetrically
      (alpha1beta1 and alpha1beta2) diliganded species show similar high rates of
      sulfhydryl reactivity and biphasic kinetics, suggesting a new conformation but
      only slight functional distortion caused by asymmetric ligation.

PMID- 22142469
TI  - Nurse practitioners, certified nurse midwives, and physician assistants in
      physician offices.
AB  - The expansion of health insurance coverage through health care reform, along with
      the aging of the population, are expected to strain the capacity for providing
      health care. Projections of the future physician workforce predict declines in
      the supply of physicians and decreasing physician work hours for primary care. An
      expansion of care delivered by nurse practitioners (NPs), certified nurse
      midwives (CNMs), and physician assistants (PAs) is often cited as a solution to
      the predicted surge in demand for health care services and calls for an
      examination of current reliance on these providers. Using a nationally based
      physician survey, we have described the employment of NPs, CNMs, and PAs among
      office-based physicians by selected physician and practice characteristics.

PMID- 22142470
TI  - Clinical and biochemical outcomes of cinacalcet treatment of familial
      hypocalciuric hypercalcemia: a case series.
AB  - INTRODUCTION: Familial hypocalciuric hypercalcemia is a rare benign autosomal
      dominant genetic disease with high penetrance. In most cases, patients with
      familial hypocalciuric hypercalcemia experience unspecific physical discomfort or
      asymptomatic disease. These patients are typically characterized by mild to
      moderately increased blood ionized calcium and a normal to slightly elevated
      serum parathyroid hormone. CASE PRESENTATION: Four female patients with familial
      hypocalciuric hypercalcemia with inactivating mutations in the CaSR gene were
      included in the treatment study. Three patients were related: two were siblings
      and one was the daughter of one of these. The ages of the related patients were
      51 years, 57 years and 35 years. All three patients were carriers of the same
      mutation. The fourth patient, unrelated to the others, was 53 years old, and a
      carrier of a novel and previously unknown mutation leading to familial
      hypocalciuric hypercalcemia. All four patients were Caucasians of Danish
      nationality. Biochemically, all patients had elevated blood ionized calcium,
      serum parathyroid hormone, serum magnesium and total serum calcium, except one,
      whose serum parathyroid hormone was within the normal range prior to treatment.
      All patients were treated with cinacalcet in a dosage of 30 mg to 60 mg per day.
      CONCLUSION: Three months after the initiation of cinacalcet treatment, all our
      patients experiencing clinical signs of hypercalcemia had improved in self 
      reported well-being and in biochemical parameters. None of our patients suffered
      adverse events to cinacalcet treatment. Biochemical markers of calcium
      homeostasis were improved and remained stable during the observation period of 12
      months (two patients), 24 and 36 months, in both the symptomatic and the
      asymptomatic patients.

PMID- 22142471
TI  - Signaling pathways activated by the phytochemical nordihydroguaiaretic acid
      contribute to a Keap1-independent regulation of Nrf2 stability: Role of glycogen
      synthase kinase-3.
AB  - Defense against oxidative stress is executed by an antioxidant program that is
      tightly controlled by the transcription factor Nrf2. The stability of Nrf2
      involves the interaction of two degradation domains, designated Neh2 and Neh6,
      with the E3 ubiquitin ligase adaptors, Keap1 and beta-TrCP, respectively. The
      regulation of Nrf2 through the Neh6 degron remains largely unexplored but
      requires GSK-3 to form a phosphodegron. In this study, the cancer-chemopreventive
      agent nordihydroguaiaretic acid (NDGA) increased the level of Nrf2 protein and
      expression of heme oxygenase-1 (HO-1) in kidney-derived LLC-PK1 and HEK293T cells
      and in wild-type mouse embryo fibroblasts (MEFs). However, NDGA did not induce HO
      1 in Nrf2(-/-) MEFs, indicating that Nrf2 is required for induction. The
      relevance of the Nrf2/HO-1 axis to antioxidant protection was further
      demonstrated by the finding that the HO-1 inhibitor stannous-mesoporphyrin
      abolished protection against hydrogen peroxide conferred by NDGA. NDGA increased
      Nrf2 and HO-1 protein levels in Keap1(-/-) MEFs, implying that Keap1-independent
      mechanisms regulate Nrf2 stability. Mutants of the Neh2 or Nrh6 domain and
      chimeric proteins comprising cyan fluorescent protein fused to Neh2 and green
      fluorescent protein fused to Neh6 exhibited longer half-lives in the presence of
      NDGA, demonstrating that NDGA targets both the Neh2 and the Neh6 degrons. In
      common with other chemopreventive agents, NDGA activated the ERK1/2, p38, JNK,
      and PI3K pathways. By using selective kinase inhibitors we found that PI3K, JNK,
      and p38 were responsible for the stabilization of Nrf2 and induction of HO-1 by
      NDGA. To explain how NDGA might up-regulate Nrf2 in a Keap1-independent manner we
      explored the participation of GSK-3beta because it controls the Neh6
      phosphodegron. Importantly, NDGA caused inhibitory phosphorylation of GSK-3beta
      at Ser9 and at Thr390, and this was associated with a substantial reduction in
      Neh6 phosphorylation. Our study demonstrates that NDGA activates Nrf2 through
      multiple signaling cascades and identifies GSK-3beta as an integrator of these
      signaling pathways and a gatekeeper of Nrf2 stability at the level of the Neh6
      phosphodegron.

PMID- 22142472
TI  - Serine-threonine kinase 38 is regulated by glycogen synthase kinase-3 and
      modulates oxidative stress-induced cell death.
AB  - Serine-threonine kinase 38 (STK38) is a member of the protein kinase A
      (PKA)/PKG/PKC-like family. In the present study, we investigated the regulatory
      mechanism of STK38 and assessed its role in the cellular stress response. Among
      various environmental stresses, STK38 was specifically activated by H(2)O(2), and
      the phosphatidylinositol 3-kinase inhibitor wortmannin or AKT inhibitor IV
      suppressed this activation. STK38 was also activated by a constitutively active
      AKT1 or by GSK-3beta inhibitor VII. The phosphorylation level of GSK-3beta was
      correlated with the STK38 activity, in response to various stimuli and in
      different cell lines. Co-immunoprecipitation analysis revealed that GSK-3beta
      physically interacted with STK38 in cells. GSK-3beta overexpression inhibited the
      H(2)O(2)-stimulated STK38 activity. GSK-3beta phosphorylated STK38 on residues S6
      and T7 in vitro, depending largely on a PKA-mediated priming phosphorylation of
      STK38 on residues S10 and S11, respectively. STK38's H(2)O(2)-stimulated activity
      was enhanced by alanine substitution at its priming sites and/or at S6 and T7,
      and it was partially reduced by a phosphomimetic mutation at S6 or T7. STK38
      knockdown enhanced the H(2)O(2)-induced JNK phosphorylation and cell death. Our
      results indicate that that GSK-3beta inhibits STK38's full activation, and
      suggest that STK38 activation is required to prevent cell death in response to
      oxidative stress.

PMID- 22142473
TI  - Resistance of neuroblastoma GI-ME-N cell line to glutathione depletion involves
      Nrf2 and heme oxygenase-1.
AB  - Cancer cell survival is known to be related to the ability to counteract
      oxidative stress, and glutathione (GSH) depletion has been proposed as a
      mechanism to sensitize cells to anticancer therapy. However, we observed that GI
      ME-N cells, a neuroblastoma cell line without MYCN amplification, are able to
      survive even if GSH-depleted by l-buthionine-(S,R)-sulfoximine (BSO). Here, we
      show that in GI-ME-N cells, BSO activates Nrf2 and up-regulates heme oxygenase-1
      (HO-1). Silencing of Nrf2 restrained HO-1 induction by BSO. Inhibition of HO-1
      and silencing of Nrf2 or HO-1 sensitized GI-ME-N cells to BSO, leading to
      reactive oxygen/nitrogen species overproduction and decreasing viability.
      Moreover, targeting the Nrf2/HO-1 axis sensitized GI-ME-N cells to etoposide more
      than GSH depletion. Therefore, we have provided evidence that in GI-ME-N cells,
      the Nrf2/HO-1 axis plays a crucial role as a protective factor against cellular
      stress, and we suggest that the inhibition of Nfr2/HO-1 signaling should be
      considered as a central target in the clinical battle against neuroblastoma.

PMID- 22142474
TI  - New antimalarial indolone-N-oxides, generating radical species, destabilize the
      host cell membrane at early stages of Plasmodium falciparum growth: role of band
      3 tyrosine phosphorylation.
AB  - Although indolone-N-oxide (INODs) genereting long-lived radicals possess
      antiplasmodial activity in the low-nanomolar range, little is known about their
      mechanism of action. To explore the molecular basis of INOD activity, we screened
      for changes in INOD-treated malaria-infected erythrocytes (Pf-RBCs) using a
      proteomics approach. At early parasite maturation stages, treatment with INODs at
      their IC(50) concentrations induced a marked tyrosine phosphorylation of the
      erythrocyte membrane protein band 3, whereas no effect was observed in control
      RBCs. After INOD treatment of Pf-RBCs we also observed: (i) accelerated formation
      of membrane aggregates containing hyperphosphorylated band 3, Syk kinase, and
      denatured hemoglobin; (ii) dose-dependent release of microvesicles containing the
      membrane aggregates; (iii) reduction in band 3 phosphorylation, Pf-RBC
      vesiculation, and antimalarial effect of INODs upon addition of Syk kinase
      inhibitors; and (iv) correlation between the IC(50) and the INOD concentrations
      required to induce band 3 phosphorylation and vesiculation. Together with
      previous data demonstrating that tyrosine phosphorylation of oxidized band 3
      promotes its dissociation from the cytoskeleton, these results suggest that INODs
      cause a profound destabilization of the Pf-RBC membrane through a mechanism
      apparently triggered by the activation of a redox signaling pathway rather than
      direct oxidative damage.

PMID- 22142475
TI  - RNA-dependent RNA polymerase 6 of rice (Oryza sativa) plays role in host defense
      against negative-strand RNA virus, Rice stripe virus.
AB  - RNA-dependent RNA polymerases (RDRs) from fungi, plants and some invertebrate
      animals play fundamental roles in antiviral defense. Here, we investigated the
      role of RDR6 in the defense of economically important rice plants against a
      negative-strand RNA virus (Rice stripe virus, RSV) that causes enormous crop
      damage. In three independent transgenic lines (OsRDR6AS line A, B and C) in which
      OsRDR6 transcription levels were reduced by 70-80% through antisense silencing,
      the infection and disease symptoms of RSV were shown to be significantly
      enhanced. The hypersusceptibilities of the OsRDR6AS plants were attributed not to
      enhanced insect infestation but to enhanced virus infection. The rise in symptoms
      was associated with the increased accumulation of RSV genomic RNA in the OsRDR6AS
      plants. The deep sequencing data showed reduced RSV-derived siRNA accumulation in
      the OsRDR6AS plants compared with the wild type plants. This is the first report
      of the antiviral role of a RDR in a monocot crop plant in the defense against a
      negative-strand RNA virus and significantly expands upon the current knowledge of
      the antiviral roles of RDRs in the defense against different types of viral
      genomes in numerous groups of plants.

PMID- 22142476
TI  - Reovirus genomes from plant-feeding insects represent a newly discovered lineage
      within the family Reoviridae.
AB  - A complex set of double-stranded RNAs (dsRNAs) was isolated from threecornered
      alfalfa hopper (Spissistilus festinus), a plant-feeding hemipteran pest. A subset
      of these dsRNAs constitute the genome of a new reovirus, provisionally designated
      Spissistilus festinus reovirus (SpFRV). SpFRV was present in threecornered
      alfalfa hopper populations in the San Joaquin Valley of California, with
      incidence ranging from 10% to 60% in 24 of 25 sample sets analyzed. The 10 dsRNA
      segments of SpFRV were completely sequenced and shown to share conserved terminal
      sequences (5'-AGAGA and CGAUGUUGU-3') of the positive-sense strand that are
      distinct from known species of the family Reoviridae. Comparisons of the RNA
      directed RNA polymerase (RdRp) indicated SpFRV is most closely related (39.1%
      amino acid identity) to another new reovirus infecting the angulate leafhopper
      (Acinopterus angulatus) and provisionally designated Acinopterus angulatus
      reovirus (AcARV). The RdRp of both viruses was distantly related to Raspberry
      latent virus RdRp at 27.0% (SpFRV) and 30.0% (AcARV) or Rice ragged stunt virus
      RdRp at 26.2% (SpFRV) and 29.0% (AcARV) amino acid identity. RdRp phylogeny
      confirmed that SpFRV and AcARV are sister taxa sharing a most recent common
      ancestor. SpFRV segment 6 encodes a protein containing two NTP binding motifs
      that are conserved in homologs of reoviruses in the subfamily Spinareovirinae.
      The protein encoded by SpFRV segment 4 was identified as a guanylyltransferase
      homolog. SpFRV segments 1, 3, and 10 encode homologs of reovirus structural
      proteins. No homologs were identified for proteins encoded by SpFRV segments 5,
      7, 8, and 9. Collectively, the low level of sequence identity with other
      reoviruses, similar segment terminal sequences, RdRp phylogeny, and host taxa
      indicate that SpFRV and AcARV may be considered members of a proposed new genus
      of the family Reoviridae (subfamily Spinareovirinae), with SpFRV assigned as the
      type species.

PMID- 22142478
TI  - An epidemiological study of the effects of statin use on airflow limitation in
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is
      considered to be a systemic inflammatory disease, and systemic inflammation has
      been noted as a factor contributing to cardiovascular disease, which is one of
      the comorbidities associated with COPD. On the other hand, pleiotropic effects,
      such as the anti-inflammatory effects of statins, have attracted attention in
      recent years, and there have been a variety of reports regarding the usefulness
      of statins for patients with COPD. METHODS: We investigated whether the use or
      non-use of statins influenced the prevalence of airflow limitation. All
      outpatients who were over the age of 40 years and who regularly visited a primary
      health care facility were invited to participate. Each participant underwent
      spirometry and completed a questionnaire regarding their clinical status, which
      was used to screen for COPD. A variety of factors that are potentially related to
      airflow limitation were assessed. RESULTS: Of the 853 patients included in the
      study, 81 (9.5%) had airflow limitation. The prevalence of airflow limitation was
      2.3% among the 89 patients with a history of statin use, which was five times
      lower than the prevalence of airflow limitation among patients who had not used
      statins (10.5%). Among the 347 patients with a history of past or current
      smoking, airflow limitation was not observed in the 30 patients who had used
      statins. However, by multivariate analysis, statin use was not significantly
      associated with a lower prevalence of airflow limitation. CONCLUSIONS: This is
      the first cross-sectional study from Japan that has demonstrated that statin use
      has a potential impact on airflow limitation in patients with COPD.

PMID- 22142477
TI  - Low genetic diversity of Squash vein yellowing virus in wild and cultivated
      cucurbits in the U.S. suggests a recent introduction.
AB  - Squash vein yellowing virus (SqVYV) isolates were collected from cultivated and
      weedy cucurbits representing major hosts and locations in the U.S. and analyzed
      to better understand the diversity and population structure. No differences in
      symptoms were observed in field-collected isolate source plants or subsequently
      inoculated greenhouse plants, and the complete genome of an SqVYV isolate from a
      wild cucurbit host (smellmelon, Cucumis melo var. dudaim) was highly similar
      (99.4% nucleotide identity, 99.3% amino acid identity) to the previously
      published type isolate from squash. Although analysis of the coat protein (CP)
      and two serine proteases (P1a and P1b) sequences for 41 isolates showed little
      diversity across seven years of sampling, it revealed two distinct groups of
      SqVYV isolates with low intra-group diversity. Our analyses also suggested that
      recombination had occurred between SqVYV isolates, similar to other ipomoviruses.
      Selection pressures on the genome regions analyzed were negative indicating
      purifying selection was occurring. The magnitude of negative selection in SqVYV
      was consistent with what has been reported for other ipomoviruses, and was
      greatest for the CP and least for the P1b. The observed genetic diversity was
      similar to that reported for Cucumber vein yellowing virus but less than that
      reported for Sweet potato mild mottle virus, Cassava brown streak virus and
      Ugandan cassava brown streak virus. Collectively, these results indicate that the
      current U.S. population of SqVYV has undergone a recent genetic bottleneck and
      was introduced from elsewhere.

PMID- 22142479
TI  - Attention deficit hyperactivity disorder among children aged 5-17 years in the
      United States, 1998-2009.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most common mental
      health disorders of childhood. The symptoms of ADHD (inattention, impulsive
      behavior, and hyperactivity) begin in childhood and often persist into adulthood.
      These symptoms frequently lead to functional impairment in academic, family, and
      social settings. The causes and risk factors for ADHD are unknown, but genetic
      factors likely play a role. Diagnosis of ADHD involves several steps, including a
      medical exam; a checklist for rating ADHD symptoms based on reports from parents,
      teachers, and sometimes the child; and an evaluation for coexisting conditions.
      Recent national surveys have documented an increase in the prevalence of ADHD
      during the past decade. This report presents recent trends in prevalence and
      differences between population subgroups of children aged 5-17 years.

PMID- 22142480
TI  - An extract of chokeberry attenuates weight gain and modulates insulin, adipogenic
      and inflammatory signalling pathways in epididymal adipose tissue of rats fed a
      fructose-rich diet.
AB  - Chokeberries are a rich source of anthocyanins, which may contribute to the
      prevention of obesity and the metabolic syndrome. The aim of the present study
      was to determine if an extract from chokeberries would reduce weight gain in rats
      fed a fructose-rich diet (FRD) and to explore the potential mechanisms related to
      insulin signalling, adipogenesis and inflammatory-related pathways. Wistar rats
      were fed a FRD for 6 weeks to induce insulin resistance, with or without
      chokeberry extract (CBE) added to the drinking-water (100 and 200 mg/kg body
      weight, daily: CBE100 and CBE200). Both doses of CBE consumption lowered
      epididymal fat, blood glucose, TAG, cholesterol and LDL-cholesterol. CBE
      consumption also elevated plasma adiponectin levels and inhibited plasma TNF
      alpha and IL6, compared with the control group. There were increases in the mRNA
      expression for Irs1, Irs2, Pi3k, Glut1, Glut4 and Gys1, and decreases in mRNA
      levels of Gsk3beta. The protein and gene expression of adiponectin and Ppargamma
      mRNA levels were up-regulated and Fabp4, Fas and Lpl mRNA levels were inhibited.
      The levels of gene expression of inflammatory cytokines, such as Il1beta, Il6 and
      Tnfalpha were lowered, and protein and gene expression of ZFP36 (zinc finger
      protein) were enhanced in the epididymal adipose tissue of the rats that consumed
      the CBE200 extract. In summary, these results suggest that the CBE decreased risk
      factors related to insulin resistance by modulating multiple pathways associated
      with insulin signalling, adipogenesis and inflammation.

PMID- 22142481
TI  - Acoustically driven photon antibunching in nanowires.
AB  - The oscillating piezoelectric field of a surface acoustic wave (SAW) is employed
      to transport photoexcited carriers, as well as to spatially control exciton
      recombination in GaAs-based nanowires (NWs) on a subns time scale. The
      experiments are carried out in core-shell NWs transferred to a SAW delay line on
      a LiNbO(3) crystal. Carriers generated in the NW by a focused laser spot are
      acoustically transferred to a second location, leading to the remote emission of
      subns light pulses synchronized with the SAW phase. The dynamics of the carrier
      transport, investigated using spatially and time-resolved photoluminescence, is
      well-reproduced by computer simulations. The high-frequency contactless
      manipulation of carriers by SAWs opens new perspectives for applications of NWs
      in opto-electronic devices operating at gigahertz frequencies. The potential of
      this approach is demonstrated by the realization of a high-frequency source of
      antibunched photons based on the acoustic transport of electrons and holes in
      (In,Ga)As NWs.

PMID- 22142482
TI  - Using the Precede-Proceed Model of Health Program Planning in breast cancer
      nursing research.
AB  - AIM: In this article, we discuss the use of the Precede-Proceed model when
      investigating health promotion options for breast cancer survivors. BACKGROUND:
      Adherence to recommended health behaviours can optimize well-being after cancer
      treatment. Guided by the Precede-Proceed approach, we studied the behaviours of
      breast cancer survivors in our health service area. DATA SOURCES: The interview
      data from the cohort of breast cancer survivors are used in this article to
      illustrate the use of Precede-Proceed in this nursing research context. Interview
      data were collected from June to December 2009. We also searched Medline, CINAHL,
      PsychInfo and PsychExtra up to 2010 for relevant literature in the English
      language to interrogate the data from other theoretical perspectives. DISCUSSION:
      The Precede-Proceed model is theoretically complex. The deductive analytic
      process guided by the model usefully explained some of the health behaviours of
      cancer survivors, although it could not explicate many other findings. A
      complementary inductive approach to the analysis and subsequent interpretation by
      way of Uncertainty in Illness Theory and other psychosocial perspectives provided
      a comprehensive account of the qualitative data that resulted in contextually
      relevant recommendations for nursing practice. IMPLICATIONS FOR NURSING: Nursing
      researchers using Precede-Proceed should maintain theoretical flexibility when
      interpreting qualitative data. Perspectives not embedded in the model might need
      to be considered to ensure that the data are analysed in a contextually relevant
      way. CONCLUSION: Precede-Proceed provides a robust framework for nursing
      researchers investigating health promotion in cancer survivors; however,
      additional theoretical lenses to those embedded in the model can enhance data
      interpretation.

PMID- 22142483
TI  - Detection and quantification of poliovirus infection using FTIR spectroscopy and
      cell culture.
AB  - BACKGROUND: In a globalized word, prevention of infectious diseases is a major
      challenge. Rapid detection of viable virus particles in water and other
      environmental samples is essential to public health risk assessment, homeland
      security and environmental protection. Current virus detection methods,
      especially assessing viral infectivity, are complex and time-consuming, making
      point-of-care detection a challenge. Faster, more sensitive, highly specific
      methods are needed to quantify potentially hazardous viral pathogens and to
      determine if suspected materials contain viable viral particles. Fourier
      transform infrared (FTIR) spectroscopy combined with cellular-based sensing, may
      offer a precise way to detect specific viruses. This approach utilizes infrared
      light to monitor changes in molecular components of cells by tracking changes in
      absorbance patterns produced following virus infection. In this work poliovirus
      (PV1) was used to evaluate the utility of FTIR spectroscopy with cell culture for
      rapid detection of infective virus particles. RESULTS: Buffalo green monkey
      kidney (BGMK) cells infected with different virus titers were studied at 1 - 12
      hours post-infection (h.p.i.). A partial least squares (PLS) regression method
      was used to analyze and model cellular responses to different infection titers
      and times post-infection. The model performs best at 8 h.p.i., resulting in an
      estimated root mean square error of cross validation (RMSECV) of 17 plaque
      forming units (PFU)/ml when using low titers of infection of 10 and 100 PFU/ml.
      Higher titers, from 103 to 106 PFU/ml, could also be reliably detected.
      CONCLUSIONS: This approach to poliovirus detection and quantification using FTIR
      spectroscopy and cell culture could potentially be extended to compare
      biochemical cell responses to infection with different viruses. This virus
      detection method could feasibly be adapted to an automated scheme for use in
      areas such as water safety monitoring and medical diagnostics.

PMID- 22142484
TI  - Management of T1 colorectal carcinoma with special reference to criteria for
      curative endoscopic resection.
AB  - BACKGROUND AND AIM: In guidelines 2010 for the treatment of colorectal cancer
      from the Japanese Society for Cancer of the Colon and Rectum (JSCCR), the
      criteria for identifying curable T1 colorectal carcinoma after endoscopic
      resection were well/moderately differentiated or papillary histologic grade, no
      vascular invasion, submucosal invasion depth less than 1000 um and budding grade
      1 (low grade). We aimed to expand these criteria. METHODS: A total of 499 T1
      colorectal carcinomas, resected endoscopically or surgically, were analyzed.
      Relationships between clinicopathologic findings and lymph node metastasis were
      evaluated. RESULTS: Lymph node metastasis was found in 41 (8.22%) of the 499
      cases. The incidence of lymph node metastasis was significantly higher in lesions
      featuring poorly differentiated/mucinous adenocarcinoma, submucosal invasion >=
      1800 um, vascular invasion, and high-grade tumor budding than in other lesions.
      Multivariate logistic regression analysis showed all of these variables to be
      independent risk factors for lymph node metastasis. When cases that met three of
      the JSCCR 2010 criteria (i.e. all but invasion < 1000 um) were considered
      together, the incidence of lymph node metastasis was only 1.2% (3/249, 95%
      confidence interval: 0.25-3.48%), and there were no cases of lymph node
      metastasis without submucosal invasion to a depth of >= 1800 um. CONCLUSIONS:
      Even in cases of colorectal carcinoma with deep submucosal invasion, the risk of
      lymph node metastasis is minimal under certain conditions. Thus, even for such
      cases, endoscopic incisional biopsy can be suitable if complete en bloc resection
      is achieved.

PMID- 22142485
TI  - Water avoidance stress induces frequency through cyclooxygenase-2 expression: a
      bladder rat model.
AB  - OBJECTIVES: Water avoidance stress is a potent psychological stressor and it is
      associated with visceral hyperalgesia, which shows degeneration of the urothelial
      layer mimicking interstitial cystitis. Cyclooxygenase-2 inhibitors have been
      recognized to ameliorate frequency both in clinical and experimental settings. We
      investigated the voiding pattern and cyclooxygenase-2 expression in a rat bladder
      model of water avoidance stress. METHODS: After being subjected to water
      avoidance stress or a sham procedure, rats underwent metabolic cage analysis and
      cystometrography. Real time reverse transcription polymerase chain reaction was
      carried out to examine cyclooxygenase-2 messenger ribonucleic acid in bladders of
      rats. Protein expression of cyclooxygenase-2 was analyzed with
      immunohistochemistry and western blotting. Furthermore, the effects of the
      cyclooxygenase-2 inhibitor, etodolac, were investigated by carrying out
      cystometrography, immunohistochemistry and western blotting. RESULTS: Metabolic
      cage analysis and cystometrography showed significantly shorter intervals and
      less volume of voiding in water avoidance stress rats. Significantly higher
      expression of cyclooxygenase-2 messenger ribonucleic acid was verified by reverse
      transcription polymerase chain reaction. Immunohistochemistry and western
      blotting showed significantly higher cyclooxygenase-2 protein levels in water
      avoidance stress bladders. Furthermore, immunohistochemistry showed high
      cyclooxygenase-2 expression exclusively in smooth muscle cells. All water
      avoidance stress-induced changes were reduced by cyclooxygenase-2 inhibitor
      pretreatment. CONCLUSIONS: Chronic stress might cause frequency through
      cyclooxygenase-2 gene upregulation in bladder smooth muscle cells. Further study
      of cyclooxygenase-2 in the water avoidance stress bladder might provide novel
      therapeutic modalities for interstitial cystitis.

PMID- 22142486
TI  - The adverse effect of an unplanned surgical excision of foot soft tissue sarcoma.
AB  - BACKGROUND: Malignant soft tissue tumors of the foot are extremely rare and thus
      can be prematurely excised without appropriate preoperative evaluation. The
      present study compares adverse effects between unplanned and planned surgical
      excisions. METHODS: We retrospectively reviewed the clinical records,
      radiographs, pathology reports and pathological specimens of 14 consecutive
      patients with soft tissue sarcoma of the foot among 592 with sarcomas between
      1973 and 2009. We then compared the incidence and clinical outcomes after
      unplanned (UT; n = 5) and planned (PT; n = 9) surgical excisions of foot
      sarcomas. RESULTS: The most frequent diagnosis was synovial sarcoma (n = 4;
      28.6%). The overall 5-year survival rates of the PT and UT groups were 65.6% and
      60.0%, respectively, and the event-free 5-year survival rates were 63.5% and
      40.0%, respectively. Event-free and overall survival rates did not significantly
      differ between the two groups. However, tumors were significantly larger in the
      PT group than in the UT group (p < 0.05). CONCLUSIONS: Unplanned resection lead
      to a relatively worse prognosis and a likelihood of recurrence despite additional
      resections. We recommend that soft tumors of the foot should only be excised
      after appropriate preoperative evaluation regardless of the size of the tumor.

PMID- 22142487
TI  - Reconstruction of the epidemic history of hepatitis B virus genotype D in
      Albania.
AB  - Despite a recent decrease in the prevalence of HBsAg in the general population,
      Albania is still highly endemic for HBV infection. Genotype D is the most
      prevalent HBV strain in the Mediterranean area. We studied the prevalence and
      distribution of HBV genotypes and subgenotypes in a total of 73 HBsAg-positive
      patients living in Albania, and reconstructed the epidemiological history of the
      most prevalent HBV D subgenotype using a "phylodynamic" framework. A time-scaled
      genealogy of the Albanian patients' and reference P gene sequences with known
      sampling dates was reconstructed using an MCMC Bayesian approach that allows
      population growth to be estimated on the basis of coalescent theory. All of the
      Albanian subjects were infected with the HBV D genotype, and a percentage varying
      from 44.4% to 100% (depending on the ethnic or risk group) were infected with
      subgenotype D2, the most prevalent in the study population (72.4%). The other
      subgenotypes present in a minority of subjects were D1 (13.8%) and D3 (13.8%).
      The Bayesian skyline plot population dynamics analysis showed that genotype D2
      entered the Albanian population in the late 1960s, and that the effective number
      of infections grew gradually until the second half of the 1980s and more rapidly
      until the mid-1990s, when it reached a plateau that still persists today. Our
      data suggest that political and socio-economic factors played an important role
      in determining the rapid spread of HBV infection in Albania.

PMID- 22142488
TI  - Population genetic structure of Meccus longipennis (Hemiptera, Reduviidae,
      Triatominae), vector of Chagas disease in West Mexico.
AB  - The originally wild species of the Meccus complex are important vectors of Chagas
      disease in Mexico. In West Mexico, Meccus longipennis plays an important
      epidemiological role. To understand the genetic structure of the domestic and
      wild populations of this species, a preliminary study with five polymorphic
      microsatellite loci was conducted. The population genetics analysis showed high
      structuring between peridomestic biotopes, with breeding subunits detected in a
      single peridomestic structure. In the wild environment, two genetic patterns were
      observed according to the biotope, possible breeding subunits in large rocky
      formations and a larger panmictic unit in agropastoral areas, suggesting
      considerable dispersal of bugs in this biotope. Moreover, the discovery of two
      foci of wild populations at the edge of Guadalajara city raises the question of
      new urban areas where the phenomenon of bug incursions into households could
      constitute a risk of transmission of Chagas disease.

PMID- 22142489
TI  - Solitary framboesiform syphilid on the scalp.

PMID- 22142491
TI  - Tunable photoemission from an excitonic antitrap.
AB  - We study the influence of lithographically defined, electrostatic trap
      configurations on the photon emission from dipolar excitons in coupled quantum
      wells. The emission is surprisingly enhanced for an excitonic antitrap compared
      to a trap configuration, an effect more pronounced for a trap with smaller
      diameter. We explain the observations by the interplay between the exciton
      formation process, the lateral charge-carrier dynamics, and the dipole-dipole
      interactions between the excitons. Exploiting this interplay allows us to
      efficiently tune the excitonic emission energy with very small intensity
      variation.

PMID- 22142490
TI  - Quantitative pulmonary imaging using computed tomography and magnetic resonance
      imaging.
AB  - Measurements of lung function, including spirometry and body plethesmography, are
      easy to perform and are the current clinical standard for assessing disease
      severity. However, these lung functional techniques do not adequately explain the
      observed variability in clinical manifestations of disease and offer little
      insight into the relationship of lung structure and function. Lung imaging and
      the image-based assessment of lung disease has matured to the extent that it is
      common for clinical, epidemiologic and genetic investigation to have a component
      dedicated to image analysis. There are several exciting imaging modalities
      currently being used for the non-invasive study of lung anatomy and function. In
      this review, we will focus on two of them; X-ray computed tomography and magnetic
      resonance imaging. Following a brief introduction of each method, we detail some
      of the most recent work being done to characterize smoking-related lung disease
      and the clinical applications of such knowledge.

PMID- 22142493
TI  - New microsatellite markers developed from Urochloa humidicola (Poaceae) and cross
      amplification in different Urochloa species.
AB  - BACKGROUND: Urochloa humidicola is a forage grass that grows in tropical regions
      and is recognized for its tolerance to seasonal flooding. It is a polyploid and
      apomictic species with high phenotypic plasticity. As molecular tools are
      important in facilitating the development of new cultivars and in the
      classification of related species, the objectives of this study were to develop
      new polymorphic microsatellite markers from an enriched library constructed from
      U. humidicola and to evaluate their transferability to other Urochloa species.
      FINDINGS: Microsatellite sequences were identified from a previously constructed
      enriched library, and specific primers were designed for 40 loci. Isolated di
      nucleotide repeat motifs were the most abundant followed by tetra-nucleotide
      repeats. Of the tested loci, 38 displayed polymorphism when screened across 34
      polyploid Urochloa sp. genotypes, including 20 accessions and six hybrids of U.
      humidicola and two accessions each from U. brizantha, U. dictyoneura, U.
      decumbens and U. ruziziensis. The number of bands per Simple Sequence Repeat
      (SSR) locus ranged from one to 29 with a mean of 11.5 bands per locus. The mean
      Polymorphism Information Content (PIC) of all loci was 0.7136, and the mean
      Discrimination Power (DP) was 0.7873. Six loci amplified in all species tested.
      STRUCTURE analysis revealed six different allelic pools, and the genetic
      similarity values analyzed using Jaccard's coefficient ranged from 0.000 to
      0.913. CONCLUSIONS: This work reports new polymorphic microsatellite markers that
      will be useful for breeding programs for Urochloa humidicola and other Urochloa
      species as well as for genetic map development, germplasm characterization,
      evolutionary and taxonomic studies and marker-assisted trait selection.

PMID- 22142492
TI  - Tissue-specific expression of Sprouty1 in mice protects against high-fat diet
      induced fat accumulation, bone loss and metabolic dysfunction.
AB  - We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor
      as a regulator of marrow progenitor cells promoting osteoblast differentiation at
      the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice
      resulted in increased bone mass and reduced body fat, while conditional knockout
      of Spry1 had the opposite effect with decreased bone mass and increased body fat.
      Because Spry1 suppresses normal fat development, we tested the hypothesis that
      Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated
      lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect
      on mice fed a high-energy diet. We studied diet-induced obesity in mice with
      fatty acid binding promoter-driven expression or conditional knockout of Spry1 in
      adipocytes. Phenotyping was performed by whole-body dual-energy X-ray
      absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null
      mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and
      led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0.05)
      lower body fat, reduced bone loss and normal metabolic function compared with
      single transgenics. This protective phenotype was associated with decreased
      circulating insulin (70 %) and leptin (54 %; P < 0.005) compared with controls on
      a high-fat diet. Additionally, Spry1 expression decreased adipose tissue
      inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue
      protects against high-fat diet-induced obesity and associated bone loss.

PMID- 22142495
TI  - Effect of pelvic floor muscle exercise programme on stress urinary incontinence
      among pregnant women.
AB  - AIM: This article is a report of a study of the effects of a pelvic floor muscle
      exercise programme on the severity of stress urinary incontinence in pregnant
      women. BACKGROUND: Pregnancy is main risk factor for the development of stress
      urinary incontinence. Stress urinary incontinence can be cured by pelvic floor
      muscle exercise which is a safe inexpensive treatment with no complications and
      does not require the use of instruments. METHODOLOGY: A quasi-experimental study,
      pre-post test with control group design was used at the antenatal care unit in a
      tertiary care hospital between June and October of 2006. The participants were 66
      pregnant women who had stress urinary incontinence with gestational ages of 20-30
      weeks. The main outcome measure was severity of stress urinary incontinence which
      comprised frequency and amount of urine leakage and perceived severity of stress
      urinary incontinence. RESULTS: After the experimental group's participation in
      the pelvic floor muscle exercise programme, the frequency and amount of urine
      leakage and the score of perceived stress urinary incontinence severity were
      significantly lower than the same scores before participation in the programme.
      In addition, women in the experimental group had frequency and volume of urine
      leakage, and score of perceived stress urinary incontinence severity after
      participation significantly lower than those in the control group. CONCLUSION:
      The 6-week pelvic floor muscle exercise programme was able to decrease the
      severity of symptoms in pregnant women with stress urinary incontinence.

PMID- 22142494
TI  - Social inequality in dynamic balance performance in an early old age Spanish
      population: the role of health and lifestyle associated factors.
AB  - This study investigates the association between socioeconomic status (SES) and
      dynamic balance performance and whether lifestyle factors explained any possible
      associations. A total of 448 nondisabled individuals, age-range 54-75 years and
      enrolled in the Active Aging Longitudinal Study of Spain in 2006, constituted the
      study population. Baseline data of this cross-sectional study were obtained by
      personal interviews and objective measures of balance performance. The present
      study shows an educational gradient in poor dynamic balance, where individuals
      with no formal education had higher risk of poor balance, also after adjustment
      for age, gender, obesity and physical activity. In addition, obesity and
      sedentary physical activity were related to poor dynamic balance. The findings
      suggest an independent effect of both SES and behavioral factors on poor balance
      performance in the older Spanish population.

PMID- 22142496
TI  - Water quality in the inshore Great Barrier Reef lagoon: Implications for long
      term monitoring and management.
AB  - Coastal and inshore areas of the Great Barrier Reef lagoon receive substantial
      amounts of material from adjacent developed catchments, which can affect the
      ecological integrity of coral reefs and other inshore ecosystems. A 5-year water
      quality monitoring dataset provides a 'base range' of water quality conditions
      for the inshore GBR lagoon and illustrates the considerable temporal and spatial
      variability in this system. Typical at many sites were high turbidity levels and
      elevated chlorophyll a and phosphorus concentrations, especially close to river
      mouths. Water quality variability was mainly driven by seasonal processes such as
      river floods and sporadic wind-driven resuspension as well as by regional
      differences such as land use. Extreme events, such as floods, caused large and
      sustained increases in water quality variables. Given the highly variable climate
      in the GBR region, long-term monitoring of marine water quality will be essential
      to detect future changes due to improved catchment management.

PMID- 22142497
TI  - Prevalence of genital mycoplasmas and ureaplasmas in men younger than 40 years-of
      age with acute epididymitis.
AB  - OBJECTIVES: Acute epididymitis is often associated with urethritis. Mycoplasma
      genitalium and Ureaplasma urealyticum have been considered as pathogens of
      urethritis. The aim of the present study was to determine the prevalence of these
      microorganisms in men with acute epididymitis. METHOD: A total of 56 men younger
      than 40 years-of-age with acute epididymitis were enrolled in the present study
      between January 2006 and June 2010. First-void urine specimens were subjected to
      culture of aerobic bacterial species, and examined for the presence of Chlamydia
      trachomatis, M. genitalium, M. hominis, U. parvum and U. urealyticum by
      polymerase chain reaction-based assays. Urethral swabs were cultured for
      Neisseria gonorrhoeae. RESULTS: The number and percentage of patients positive
      for each microorganism were as follows: Gram-negative bacilli, 2% and 3.6%; Gram
      positive cocci, 23% and 41.1%; N. gonorrhoeae, 3% and 5.4%; C. trachomatis, 28%
      and 50.0%; M. genitalium, 5% and 8.9%; M. hominis, 6% and 10.7%; U. parvum, 6%
      and 10.7%; and U. urealyticum, 5% and 8.9%. Among 25 men with non-chlamydial non
      gonococcal epididymitis, who were negative for Gram-negative bacilli, M.
      genitalium or U. urealyticum was detected in one man each (4.0%), and M. hominis
      and/or U. parvum was detected in five (20.0%). CONCLUSION: In men younger than 40
      years-of-age with acute epididymitis, C. trachomatis is a major pathogen. The
      prevalence of genital mycoplasmas and ureaplasmas are lower, and the role of
      genital mycoplasmas and ureaplasmas in the development of acute epididymitis
      remains to be determined.

PMID- 22142498
TI  - Nonenhanced ECG-gated quiescent-interval single-shot MRA (QISS-MRA) of the lower
      extremities: comparison with contrast-enhanced MRA.
AB  - AIM: To evaluate electrocardiogram (ECG)-gated quiescent-interval single-shot
      magnetic resonance angiography (QISS-MRA) for nonenhanced assessment of
      peripheral artery occlusive disease (PAOD) using contrast-enhanced MRA (CE-MRA)
      as the reference standard. MATERIALS AND METHODS: Twenty-seven patients (mean age
      66.6 +/- 10.8 years) with PAOD were included in the study. QISS-MRA and CE-MRA of
      the lower extremity were performed using a 1.5 T MR scanner. In each patient,
      subjective image quality and the degree of stenosis were evaluated on a four
      point scale for 15 predefined arterial segments. RESULTS: Twenty-five of the 27
      patients were considered for analysis. Subjective image quality of QISS-MRA was
      significantly lower for the distal aorta, pelvic arteries, and femoral arteries
      as compared to CE-MRA (p < 0.01), while no significant difference was found for
      other vascular segments. The degree of stenosis was overestimated with QISS-MRA
      in 23 of 365 (6.3%) segments and underestimated in two of 365 (0.5%) segments. As
      compared to CE-MRA, QISS-MRA had a high sensitivity (98.6%), specificity (96%) as
      well as positive and negative predictive value (88.7 and 99.6%, respectively) for
      the detection of significant stenosis (>=50%). CONCLUSION: ECG-gated QISS-MRA is
      a promising imaging technique for reliable assessment of PAOD without the use of
      contrast material.

PMID- 22142500
TI  - And the rest.

PMID- 22142499
TI  - Three-dimensional isotropic T2-weighted cervical MRI at 3T: comparison with two
      dimensional T2-weighted sequences.
AB  - AIM: To compare three-dimensional (3D) isotropic T2-weighted magnetic resonance
      imaging (MRI) sequences and reformation with two-dimensional (2D) T2-weighted
      sequences regarding image quality of the cervical spine at 3T. MATERIALS AND
      METHODS: A phantom study was performed using a water-filled cylinder. The signal
      to-noise and image homogeneity were evaluated. Fourteen (n=14) volunteers were
      examined at 3T using 3D isotropic T2-weighted sagittal and conventional 2D T2
      weighted sagittal, axial, and oblique sagittal MRI. Multiplanar reformation (MPR)
      of the 3D T2-weighted sagittal dataset was performed simultaneously with image
      evaluation. In addition to artefact assessment, the visibility of anatomical
      structures in the 3D and 2D sequences was qualitatively assessed by two
      radiologists independently. Cohen's kappa and Wilcoxon signed rank test were used
      for the statistical analysis. RESULT: The 3D isotropic T2-weighted sequence
      resulted in the highest signal-to-noise ratio (SNR) and lowest non-uniformity
      (NU) among the sequences in the phantom study. Quantitative evaluation revealed
      lower NU values of the cerebrospinal fluid (CSF) and muscles in 2D T2-weighted
      sagittal sequences compared to the 3D volume isotropic turbo spin-echo
      acquisition (VISTA) sequence. The other NU values revealed no statistically
      significant difference between the 2D turbo spin-echo (TSE) and 3D VISTA
      sequences (0.059<p<0.959). 3D VISTA images showed significantly fewer CSF flow
      artefacts (p<0.001) and better delineated intradural nerve rootlets (p=0.001) and
      neural foramina (p=0.016) compared to 2D sequences. CONCLUSION: A 3D T2 weighted
      sequence is superior to conventional 2D sequences for the delineation of
      intradural nerve rootlets and neural foramina and is less affected by CSF flow
      artefacts.

PMID- 22142501
TI  - Persistent or recurrent varicocoele after failed varicocoelectomy: outcome in
      patients treated using percutaneous transcatheter embolization.
AB  - AIM: To determine the efficacy of percutaneous transcatheter embolization in the
      management of patients with spermatic varicocoeles persisting or recurring after
      surgery. MATERIALS AND METHODS: Over a period of 10 years, 28 patients (age range
      13-55 years) were referred for percutaneous transcatheter embolization of
      postsurgical, recurrent varicocoeles. Medical documents were retrospectively
      reviewed to evaluate past surgical history, subjective symptoms, and results of
      scrotal examination, ultrasound, and semen parameters. Pre-embolization venograms
      were analysed to assess the anatomy of the testicular vein. The technical and
      clinical outcomes of embolization were then determined. RESULTS: The 28 patients
      included in the study had undergone laparoscopic varicocoelectomy (39.3%), high
      retroperitoneal ligation (25%), or inguinal ligation (25%). Subjective symptoms
      were scrotal pain (60.7%) and a palpable scrotal mass (50%) exclusively on the
      left side. Venograms revealed abnormalities of the left testicular vein in all
      cases. Embolization was technically successful in all but two cases, thus
      yielding an occlusion rate of 93%; a single case of suspected thrombophlebitis
      was the only complication. After excluding two, technically unsuccessful cases
      and one patient who was lost to follow-up, 25 patients underwent scrotal
      examination after embolization, which revealed complete resolution in 20 cases
      (80%), partial improvement in four cases (16%), and no improvement in a single
      case (4%). Among the follow-up group of patients, of the 12 who initially
      presented with scrotal pain, six (50%) were symptom-free and four (33.3%) had
      partial improvement. CONCLUSION: Percutaneous transcatheter embolization of the
      testicular vein is technically feasible and effective for managing postsurgical
      recurrent varicocoeles.

PMID- 22142503
TI  - Fetal counselling for surgical conditions.
AB  - Foetal counselling is best achieved by a multidisciplinary team that can
      favourably influence the perinatal management of prenatally diagnosed anomalies
      and provide this information to prospective parents. Prenatal diagnosis has
      remarkably improved our understanding of surgically correctable congenital
      malformations. It has allowed us to influence the delivery of the baby, offer
      prenatal surgical management and discuss the options of termination of pregnancy
      for seriously handicapping or lethal conditions. Antenatal diagnosis has also
      defined an in utero mortality for some lesions such as diaphragmatic hernia and
      sacrococcygeal teratoma so that true outcomes can be measured. The limitation of
      in-utero diagnosis cannot be ignored. The aim of prenatal counselling is to
      provide information to prospective parents on foetal outcomes, possible
      interventions, appropriate setting, time and route of delivery and expected
      postnatal outcomes, immediate and long term.

PMID- 22142502
TI  - Short- and long-term reproductive effects of prenatal and lactational growth
      restriction caused by maternal diabetes in male rats.
AB  - BACKGROUND: A suboptimal intrauterine environment may have a detrimental effect
      on gonadal development and thereby increases the risk for reproductive disorders
      and infertility in adult life. Here, we used uncontrolled maternal diabetes as a
      model to provoke pre- and perinatal growth restriction and evaluate the sexual
      development of rat male offspring. METHODS: Maternal diabetes was induced in the
      dams through administration of a single i.v. dose of 40 mg/kg streptozotocin, 7
      days before mating. Female rats presenting glycemic levels above 200 mg/dL after
      the induction were selected for the experiment. The male offspring was analyzed
      at different phases of sexual development, i.e., peripuberty, postpuberty and
      adulthood. RESULTS: Body weight and blood glucose levels of pups, on the third
      postnatal day, were lower in the offspring of diabetic dams compared to controls.
      Maternal diabetes also provoked delayed testicular descent and preputial
      separation. In the offspring of diabetic dams the weight of reproductive organs
      at 40, 60 and 90 days-old was lower, as well as sperm reserves and sperm transit
      time through the epididymis. However the plasma testosterone levels were not
      different among experimental groups. CONCLUSIONS: It is difficult to isolate the
      effects directly from diabetes and those from IUGR. Although the exposure to
      hyperglycemic environment during prenatal life and lactation delayed the onset of
      puberty in male rats, the IUGR, in the studied model, did not influenced the
      structural organization of the male gonads of the offspring at any point during
      sexual development. However the decrease in sperm reserves in epididymal cauda
      and the acceleration in sperm transit time in this portion of epididymis may lead
      to an impairment of sperm quality and fertility potential in these animals.
      Additional studies are needed in attempt to investigate the fertility of animals
      with intrauterine growth restriction by maternal diabetes and possible
      multigenerational effects.

PMID- 22142504
TI  - Using rice straw fermentation liquor to produce bioflocculants during an
      anaerobic dry fermentation process.
AB  - In this study, fermentation liquor from rice straw was used to produce
      bioflocculants during a dry fermentation process. Acetic acid and butyric acid
      were the predominant VFAs during the process. A compound bioflocculant producing
      inoculum, F(+) was inoculated into compound media in which fermentation liquor
      and conventional bioflocculants medium at different ratios. The maximum
      flocculation activity, 92.45% was achieved when 100-day fermentation liquor and
      conventional bioflocculants medium were mixed at an equal ratio. Furthermore, 454
      pyrosequencing technology was used to measure bacterial diversity on the 25th day
      of operation, which was a period of rapid VFA accumulating. A total of 2110
      sequences were obtained, and were found to be affiliated with 8 phylogenetic
      groups, including Actinobacteria, Acidobacteria, Bacteroidetes, Firmicutes,
      Proteobacteria, Chloroflexi, Spirochaetes and Synergistetes. Notably, Firmicutes
      (92.3%) was the dominant microbial population, followed by Actinobacteria (2.37%)
      and Proteobacteria (1.04%).

PMID- 22142505
TI  - Effect of composting on the removal of semivolatile organic chemicals (SVOCs)
      from sewage sludge.
AB  - In order to investigate the occurrence and removal of semivolatile organic
      chemicals (SVOCs) in the compost of sewage sludge, three different composting
      treatments, including manual turned compost (MTC), intermittent aerated compost
      (IAC), and naturally aerated compost (NAC) were conducted. Thirty SVOCs in
      composts were Soxhlet-extracted and analyzed by GC/MS. After 56 days of
      composting, the total concentrations of 16 polycyclic aromatic hydrocarbons
      (?PAHs) ranged from 0.55 to 8.20 mg kg(-1) dry weight, decreasing in order of
      IAC>MTC>NAC. The total concentrations of six phthalic acid esters (?PAEs), five
      chlorobenzenes or three nitroaromatic compounds were less than 5.0 mg kg(-1).
      Compared with the initial concentrations in sewage sludge, a significant
      reduction of ?PAHs, ?PAEs and chlorobenzenes was observed. The removal rates of
      ?PAHs and ?PAEs ranged from 54.6% to 75.9% and from 58.3% to 90.6%, respectively.
      Compared with different composting processes, MTC showed the highest potential
      for removal of SVOCs.

PMID- 22142506
TI  - Determination of the intrinsic kinetic parameters of sulfide-oxidizing
      autotrophic denitrification in differential reactors containing immobilized
      biomass.
AB  - Nitrogen removal coupled with sulfide oxidation has potential for the treatment
      of effluents from anaerobic reactors because they contain sulfide, which can be
      used as an endogenous electron donor for denitrification. This work evaluated the
      intrinsic kinetics of sulfide-oxidizing autotrophic denitrification via nitrate
      and nitrite in systems containing attached cells. Differential reactors were fed
      with nitrified synthetic domestic sewage and different sulfide concentrations.
      The intrinsic kinetic parameters of nitrogen removal were determined when the
      mass transfer resistance was negligible. This bioprocess could be described by a
      half-order kinetic model for biofilms. The half-order kinetic coefficients ranged
      from 0.425 to 0.658 mg N(1/2) L(-1/2) h(-1) for denitrification via nitrite and
      from 0.190 to 0.609 mg N(1/2) L(-1/2) h(-1) for denitrification via nitrate. In
      this latter, the lower value was due to the use of electrons donated from
      intermediary sulfur compounds whose formation and subsequent consumption were
      detected.

PMID- 22142507
TI  - Immobilization of biocatalysts for enzymatic polymerizations: possibilities,
      advantages, applications.
AB  - Biotechnology also holds tremendous opportunities for realizing functional
      polymeric materials. Biocatalytic pathways to polymeric materials are an emerging
      research area with not only enormous scientific and technological promise, but
      also a tremendous impact on environmental issues. Many of the enzymatic
      polymerizations reported proceed in organic solvents. However, enzymes mostly
      show none of their profound characteristics in organic solvents and can easily
      denature under industrial conditions. Therefore, natural enzymes seldom have the
      features adequate to be used as industrial catalysts in organic synthesis. The
      productivity of enzymatic processes is often low due to substrate and/or product
      inhibition. An important route to improving enzyme performance in non-natural
      environments is to immobilize them. In this review we will first summarize some
      of the most prominent examples of enzymatic polymerizations and will subsequently
      review the most important immobilization routes that are used for the
      immobilization of biocatalysts relevant to the field of enzymatic
      polymerizations.

PMID- 22142508
TI  - Acute energy compensation and macronutrient intake following exercise in active
      and inactive males who are normal weight.
AB  - Acute energy and macronutrient intake following an Exercise and Control protocol
      was compared to determine if active, normal-weight males regulate acute energy
      intake better, demonstrating more acute accurate energy compensation
      capabilities, than inactive, normal-weight males after exercise. Males (21.2+/
      1.9 years) of normal percent body fat (10.0-18.0%) and body mass index (23.4+/
      1.7 kg/m(2)), exercising >=150 min/week (Active: n=10) or <=60 min/week
      (Inactive: n=10), completed two protocols, counterbalanced across participants.
      The exercise protocol (Exercise) was 45-min on a cycle ergometer and the Control
      protocol consisted of 45-min of reading. Sixty minutes after protocols, an ad
      libitum meal was provided. Energy and macronutrient intake from the meal was
      determined. Inactive ate significantly less energy in the ad libitum meal in
      Exercise as compared to Control, demonstrating acute negative energy compensation
      (consumed less in the meal while expending more energy in Exercise as compared to
      Control). Active had no difference in meal energy intake between the protocols,
      but due to Inactive's reduced acute energy intake in Exercise, Active
      demonstrated better acute energy compensation than Inactive. No difference in
      meal macronutrient intake was found. Overall, Active demonstrated better acute
      energy compensation than Inactive.

PMID- 22142509
TI  - Diet quality is related to eating competence in cross-sectional sample of low
      income females surveyed in Pennsylvania.
AB  - Women participants of two federally administered nutrition education programs
      (n=149, 56% white, 64% food secure, 86% 18-50 years of age,) completed telephone
      interviews that included three 24-hour dietary recalls and the Satter Eating
      Competence Inventory. Eating competence is delineated by an Inventory score>=32.
      Competent eaters had significantly greater intakes of fiber, vitamin A, vitamin
      E, vitamin C, most B-vitamins, magnesium, iron, zinc, potassium and a higher
      Healthy Eating Index. Two dietary patterns defined as Prudent and Western were
      observed. The Prudent pattern was correlated with eating competence and
      characterized by more healthful foods such as fruits, vegetables and low-fat
      dairy products. The Western pattern, characterized by foods higher in fat, salt,
      and sugar, was not related to eating competence. Findings suggest that dietary
      guidance using an eating competence approach for low-income women is compatible
      with goals to improve dietary quality and eating patterns.

PMID- 22142510
TI  - Restrained eating is related to accelerated reaction to high caloric foods and
      cardiac autonomic dysregulation.
AB  - Cognitive bias to food-cues and cardiac autonomic dysregulation have both been
      related to disordered eating behavior in previous research. The present study
      investigated two possible measures of self-regulatory ability in restrained
      eaters: resistance to distractor interference and vagal-cardiac control. Young
      women (N=47) performed a flanker task involving high caloric food-cues or neutral
      pictures. Vagal-cardiac activity was calculated from baseline heart rate
      recordings at rest. Restrained eaters did not differ from unrestrained eaters in
      resistance to distractor interference. However, restrained eaters showed shorter
      reaction times to high-calorie food-cues as compared to neutral pictures than
      unrestrained eaters. This attentional bias was further related to low dieting
      success. Moreover, restrained eating was associated with low parasympathetic
      activation and sympathovagal imbalance, independent of current body mass. Both
      attentional bias and cardiac autonomic dysregulation were related to self
      reported weight fluctuations. Results are discussed in terms of possible adverse
      consequences of weight cycling in young women and low self-regulatory ability in
      restrained eaters.

PMID- 22142511
TI  - Plasticity of TOM complex assembly in skeletal muscle mitochondria in response to
      chronic contractile activity.
AB  - We investigated the assembly of the TOM complex within skeletal muscle under
      conditions of chronic contractile activity-induced mitochondrial biogenesis.
      Tom40 import into mitochondria was increased by chronic contractile activity, as
      was its time-dependent assembly into the TOM complex. These changes coincided
      with contractile activity-induced augmentations in the expression of key protein
      import machinery components Tim17, Tim23, and Tom22, as well as the cytosolic
      chaperone Hsp90. These data indicate the adaptability of the TOM protein import
      complex and suggest a regulatory role for the assembly of this complex in
      exercise-induced mitochondrial biogenesis.

PMID- 22142512
TI  - CRP promotes MMP-10 expression via c-Raf/MEK/ERK and JAK1/ERK pathways in
      cardiomyocytes.
AB  - C-reactive protein (CRP) was reported to be a predictor for left ventricular (LV)
      remodeling. Matrix metalloproteinase (MMP)-10 participates in the LV remodeling
      process. However, the intrinsic relationship between CRP and MMP-10 in
      cardiomyocytes remains unclear. The purpose of this study is to observe whether
      CRP may promote MMP-10 expression, and if so, to clarify signaling pathways to be
      involved in CRP-induced MMP-10 expression in cardiomyocytes. We observed in
      cultured cardiomyocytes that CRP at a dose of 5 MUg/ml increased MMP-10
      expression and activity in a time-dependent manner, as measured by real-time
      polymerase chain reaction (PCR), western blots, and casein zymography analysis.
      We hypothesized that signal pathways of mitogen-activated protein kinases (MAPKs)
      and Janus kinases (JAKs)/signal transducers and activators of transcription
      (STATs) might be involved in CRP-induced MMP-10 expression. Our results showed
      that CRP markedly activated c-Raf/MEK/ERK and JAK1/ERK signaling pathways but not
      JAK1/STAT3 signaling pathway by using the phosphor-specific antibodies against
      these pathways, and blockages of c-Raf/MEK/ERK and JAK1/ERK signaling pathways by
      the specific ERK1/2 inhibitor U0126 and JAK1 inhibitor piceatannol could
      significantly decrease CRP-induced MMP-10 expression. In addition, we
      demonstrated that the DNA binding sites of AP-1 and STAT3 in the nucleus of
      cardiomyocytes mediated CRP-induced MMP-10 expression. In conclusion, we
      demonstrated that CRP promoted MMP-10 expression and activity in cardiomyocytes,
      and clarified that c-Raf/MEK/ERK and JAK1/ERK signaling pathways were involved in
      MMP-10 expression regulation via activation of DNA binding sites for AP-1 and
      STAT3 in cardiomyocytes. Our findings suggest that CRP acts as a predictor for LV
      remodeling might be associated with its promotion effect on MMP-10 expression and
      activity.

PMID- 22142514
TI  - Beliefs underlying blood donors' intentions to donate during two phases of an
      avian influenza outbreak.
AB  - Using a Theory of Planned Behavior (TPB) framework the current study explored the
      beliefs of current blood donors (N=172) about donating during a low and high-risk
      phase of a potential avian influenza outbreak. While the majority of behavioral,
      normative, and control beliefs identified in preliminary research differed as a
      function of donors' intentions to donate during both phases of an avian influenza
      outbreak, regression analyses suggested that the targeting of different specific
      beliefs during each phase of an outbreak would yield most benefit in bolstering
      donors' intentions to remain donating. The findings provide insight in how to
      best motivate donors in different phases of an avian influenza outbreak.

PMID- 22142513
TI  - PDCD6 additively cooperates with anti-cancer drugs through activation of NF
      kappaB pathways.
AB  - The expression of programmed cell death 6 (PDCD6) is known to be down-regulated
      in cancer cell lines and ovarian cancer tissues compared to normal cells and
      tissues. In the current study, we characterized the specific function of PDCD6 as
      a novel pro-apoptotic protein. To define the roles of PDCD6 and cisplatin in
      tumorigenesis, we either over-expressed PDCD6 or treated it with cisplatin in
      SKOV-3 ovarian cancer cells. Both PDCD6 and cisplatin respectively inhibited
      cancer cell proliferation in a dose-dependent manner. The combined treatment of
      PDCD6 and cisplatin was more effective at suppressing cell growth than with
      either drug treatment alone, but had no effect with the treatment of caspase-3
      and caspase-9 inhibitors. Cleavages of caspase-3, -8, -9, and poly (ADP-ribose)
      polymerase (PARP) in PDCD6-overexpressing cells were significantly increased
      after cisplatin treatment. Cell cycle analysis highly correlated with down
      regulation of cyclin D1 and CDK4, and the induction of p16 and p27 as a cyclin
      dependent kinase inhibitor. Additionally, PDCD6 also suppressed the
      phosphorylation of signaling regulators downstream of PI3K, including PDK1 and
      Akt. PDCD6 promotes TNFalpha-dependent apoptosis through the activation of NF
      kappaB signaling pathways, increasing Bax, p53, and p21 expression, while also
      down-regulating Bcl-2 and Bcl-xL expression. The p21 and p53 promoter luciferase
      activities were enhanced by PDCD6, while there was no affect in p53(-/-) and p21(
      /-). At the same time, p53 activity was confirmed by UV irradiation and siPDCD6.
      Taken together, these results provide evidence that PDCD6 can mediate the pro
      apoptotic activity of cisplatin or TNFalpha through the down-regulation of NF
      kappaB expression.

PMID- 22142515
TI  - Symptoms and quality of life in underweight gastroesophageal reflux disease
      patients and therapeutic responses to proton pump inhibitors.
AB  - BACKGROUND AND AIM: A correlation to obesity has been reported in patients with
      gastroesophageal reflux disease (GERD). However, insufficient data have been
      obtained regarding underweight GERD patients. Post hoc analysis of a multicenter
      prospective cohort study was conducted to evaluate subjective symptoms and health
      related quality of life (HRQOL) in underweight GERD patients (body mass index
      [BMI] < 18.5) and to evaluate therapeutic response to proton pump inhibitors.
      METHODS: A total of 2646 patients who underwent endoscopy were classified by BMI
      and analyzed. Rabeprazole was administered for 8 weeks. Subjective symptoms and
      HRQOL were assessed using questionnaires (F-Scale and SF-8TM). RESULTS: Baseline
      endoscopy revealed 29.2% of patients had non-erosive reflux disease (NERD).
      Underweight status was identified in 5.8% of GERD patients, and mean baseline
      symptoms score and SF-8 physical component summary (PCS) score were 18.6 and
      42.4, respectively, reflecting greater impairment compared with the values of
      15.4 and 45.6 in normal-weight patients (BMI >= 22 but < 25). Treatment with
      rabeprazole resulted in a decrease from 18.6 at baseline to 6.7 at week 8 in
      underweight reflux esophagitis subjects, and from 15.0 to 6.3 in underweight NERD
      patients. PCS score improved in underweight patients. These changes were about
      the same as in normal-weight or obese patients. CONCLUSIONS: Japanese GERD
      patients are often obese, as reported previously, but some GERD patients are
      underweight. Baseline symptoms and QOL in underweight GERD patients tended to be
      more severe than in normal-weight patients, but therapeutic response with proton
      pump inhibitors was about the same as in normal-weight or obese patients.

PMID- 22142516
TI  - Effect of nalfurafine hydrochloride on pruritus and anxiety level in hemodialysis
      patients.

PMID- 22142518
TI  - Synthesis of pillar[5]arene dimers and their cooperative binding toward some
      neutral guests.
AB  - Three pillar[5]arene dimers, bridged by a flexible aliphatic chain (H1) or a
      relatively rigid phenylene unit (H2 and H3), were synthesized, with the possible
      synthetic strategies being discussed. The dimers could significantly enhance the
      binding affinities toward neutral model substrates in comparison with monomeric
      1,4-dimethoxypillar[5]arene (H4) through the cooperative binding of two
      pillar[5]arene moieties. The molecular binding ability and selectivity are
      discussed from the viewpoints of the size/shape-fit concept and multiple
      recognition mechanism.

PMID- 22142517
TI  - Dietary and physical activity behaviours related to obesity-specific quality of
      life and work productivity: baseline results from a worksite trial.
AB  - Obesity is associated with impaired health-related quality of life (QOL) and
      reduced productivity; less is known about the effect of dietary factors. The
      present study investigated how dietary behaviours, physical activity and BMI
      relate to weight-specific QOL and work productivity. The study was conducted in
      thirty-one small blue-collar and service industry worksites in Seattle.
      Participants were 747 employees (33.5 % non-White). Measures included self
      reported servings of fruits and vegetables, dietary behaviours such as fast food
      consumption, Godin free-time physical activity scores, measured height and
      weight, Obesity and Weight-Loss QOL (OWLQOL) scores, and Work Limitations
      Questionnaire scores. Baseline data were analysed using linear mixed models
      separately for men (n 348) and women (n 399), since sex modified the effects. BMI
      was negatively associated with OWLQOL in both women (P < 0.001) and men (P <
      0.001). The linear effect estimate for OWLQOL scores associated with a one
      category increase in BMI was 30 (95 % CI 25, 44) % for women and 14 (95 % CI 10,
      17) % for men. BMI was positively associated with productivity loss only in women
      (exp(slope) = 1.46, 95 % CI 1.02, 2.11, P = 0.04). Eating while doing another
      activity was negatively associated with OWLQOL scores in men (P = 0.0006,
      independent of BMI) and with productivity in women (P = 0.04, although the effect
      diminished when adjusting for BMI). Fast-food meals were associated with
      decreased productivity in men (P = 0.038, independent of BMI). The results
      suggest that obesogenic dietary behaviours and higher BMI are associated with
      decreased QOL and productivity to different degrees in women and men.

PMID- 22142519
TI  - Link between chronic obstructive pulmonary disease and coronary artery disease:
      implication for clinical practice.
AB  - Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD)
      are global epidemics that incur significant morbidity and mortality. These
      diseases are frequently found in combination, and they can also be found
      independent of the common causal factors, primarily smoking. Both conditions are
      systemic disorders with overlapping mechanisms and pathophysiologic processes.
      CAD has a strong effect on the severity and prognosis of COPD and vice versa,
      including acute exacerbations. Even the most recent practical clinical
      recommendations driven by Clinical Practice Guidelines still focus on one disease
      at a time, and do not provide advice for the management of patients with
      associated chronic conditions. COPD should be approached in a more comprehensive
      manner, including the treatment of cardiac comorbidities, particularly CAD. To
      focus treatment on these comorbidities might modify the natural course of the
      disease in patients with COPD who may not find relief from treatment of COPD
      alone.

PMID- 22142520
TI  - Can adequate treatment influence the postembolization syndrome and cytokine
      release in patients undergoing iatrogenic renal artery embolization?
AB  - The complete renal artery embolization is an alternative to surgical nephrectomy
      in seriously ill patients. Iatrogenic embolization can be used in many different
      conditions. Refractory nephrotic syndrome represents a very rare indication for
      embolization. Complete renal artery embolization has usually been complicated by
      postembolization syndrome (PES) which is characterized by flank pain and fever.
      Possible immunologic contribution to the PES leads some authors to the
      administration of corticosteroids to the patients undergoing embolization. We
      report here a cohort of 13 patients undergoing complete embolization of total 21
      kidneys due to refractory nephrotic syndrome non-responding to the various
      specific treatment regimes. We treated our patients undergoing renal artery
      embolization according to special protocol containing combination of antibiotic
      drugs and corticosteroids (CS) to diminish PES and evaluated its influence to the
      cytokine production. The incidence of PES was less frequent and milder in
      comparison with the historical group of patients. Significant decrease in plasma
      levels of tumor necrosis factor alpha during first post-embolization day (8.37
      pre- vs. 5.74 pg/ml post-embolization, P=0.0002) could partially explain the
      reduction of PES symptoms. The procedure was not complicated by severe
      complications and represents an elegant alternative to surgical procedure. The
      accurate timing of the embolization remains a controversial point in this
      intervention.

PMID- 22142521
TI  - Preoperative prostate specific antigen and prostate volume are significant
      predictors of seminal vesicle invasion in patients with prostate cancer.
AB  - To evaluate the potential role of several clinical and pathological parameters in
      prediction of seminal vesicle invasion in patients with clinically localized
      prostate cancer undergoing radical prostatectomy. We retrospectively analyzed the
      medical records of patients who undergone radical prostatectomy from January 2005
      until November 2010. Patients age, prostate volume, PSA, PSA density, percent of
      cancer in prostate biopsy material, Gleason summary, 1st Gleason pattern, 2nd
      Gleason pattern and the presence of high grade prostatic intraepithelial
      neoplasia were studied for their predictive ability. Two hundred and seventeen
      patients analyzed and 13.8% of them had seminal vesicle invasion in the final
      histopathological examination of the surgical specimen. A significant difference
      in PSA values, PSA density, percentage of cancer in biopsy material, biopsy
      Gleason score and 1st Gleason pattern was noticed between patients with and
      without seminal vesicle invasion. In univariate analysis, PSA, PSA density,
      prostate volume, percentage of cancer in biopsy material, biopsy Gleason score
      and 1st Gleason pattern found significant. However, in multivariate analysis,
      only PSA (p=0.008) and prostate volume (p=0.027) were found to be significant
      predictors. PSA >= 10 ng/ml and prostate volume <= 41 ml was shown to be the
      optimal cut-off values for seminal vesicle invasion in receiver operating curve
      analysis. PSA and prostate volume should be considered significant predictors for
      adverse pathology of the seminal vesicles in patients planned for surgical
      treatment of prostate cancer. This is of great concern especially in cases that a
      seminal vesicle sparing technique is planned.

PMID- 22142522
TI  - Lack of association between rs1024611 (-2581 A/G) polymorphism in CC-chemokine
      Ligand 2 and susceptibility to pulmonary Tuberculosis in Zahedan, Southeast Iran.
AB  - Approximately 5-10% of subjects infected with Mycobacterium tuberculosis develop
      active tuberculosis. It has been proposed that genetic factors determine the
      host's vulnerability to tuberculosis. Chemokine (C-C motif) ligand 2 (CCL2),
      commonly known as monocyte chemoattractant protein-1 (MCP-1), plays a key role in
      protective immunity against M. tuberculosis. The present study was aimed to
      determine if there was an association between -2581 A/G single nucleotide
      polymorphism of CCL2 and pulmonary tuberculosis (PTB) in a sample of Iranian
      subjects. This case-control study was performed on 142 PTB and 166 healthy
      subjects. The polymorphism of CCL2 (rs1024611) was determined using tetra
      amplification refractory mutational system-polymerase chain reaction (tetra ARMS
      PCR). There were no significant differences between PTB patients and control
      subjects regarding -2581 A/G single nucleotide polymorphism of CCL2. In
      conclusion, our results do not support an association of -2581 A/G polymorphism
      of CCL2 with PTB susceptibility.

PMID- 22142523
TI  - Pulsed radiofrequency therapy versus greater occipital nerve block in the
      management of refractory cervicogenic headache - a pilot study.
AB  - The aim of this pilot study was to compare the efficacy of pulsed radiofrequency
      to the greater occipital nerve versus a greater occipital nerve block with a
      mixture of local anaesthetic and steroid in the management of refractory
      cervicogenic headache. We enrolled 30 patients suffering from refractory
      cervicogenic headache. Patients were randomly allocated into two groups of
      fifteen. A greater occipital nerve block with steroid was utilised in group A,
      while a pulsed radiofrequency treatment was employed in group B. Success of both
      procedures was evaluated by comparing pre and post intervention Visual Analogue
      Scale of pain, Medication Quantification Scale - III. and Global Perceived Effect
      at three and 9 months after the procedures. At three months post therapy a
      significant decrease in Visual Analogue Scale (p<0.001) was identified (3.2
      points in group A, 3.3 points in group B respectively). In group B pain remained
      reduced even after 9 months (p<0.001) when compared to pre treatment scores. The
      consumption of analgesic medication was reduced significantly in both groups at
      three months (p<0.001) and 9 months (p<0.01), respectively. No serious
      complication was noted. Greater occipital nerve block is a safe, efficient
      technique in the management of cervicogenic headaches. Despite the lack of high
      quality scientific evidence (level III or IV) in the literature, we have
      extensive experience with steroid application and pulsed radiofrequency to the
      greater occipital nerve and report the beneficial results in our study.

PMID- 22142524
TI  - Ameliorative effects of curcumin on the spermatozoon tail length, count, motility
      and testosterone serum level in metronidazole-treated mice.
AB  - Metronidazole (MTZ) is used as an antiparasitic drug. Curcumin is considered as
      anti-oxidant and anti-inflammatory agent. The ameliorative effects of curcumin on
      MTZ induced toxicity on mice spermatozoon tail length, count, motility and
      testosterone level were investigated. MTZ was administered in 500 and 165 (high
      and therapeutic doses) mg/kg/day, with and without curcumin (100 mg/kg/day).
      After 16 days the above parameters were assessed. Spermatozoon count and motility
      and serum testosterone level MTZ-treated (500 and 165) mice were reduced. In the
      mice treated with MTZ+curcumin these parameters decreased but in a lesser extent
      than the MTZ-treated animals. Mid-piece and total lengths of the spermatozoon
      tail in control animals were 31.6 +/- 9.0 MUm and 100.3 +/- 15.0 MUm and in the
      mice treated with high doses (500) of MTZ were reduced. The mid-piece and total
      spermatozoon tail length has been decreased in a lesser extent in the mice
      treated with high dose MTZ+curcumin than the mice treated with high dose MTZ
      (p<0.01). But the length was not changed in animals treated with therapeutic dose
      of MTZ. It means curcumin treated animals had ~52% and ~39% average increase in
      mid-piece and total lengths in comparison with the MTZ-treated (500) animals.
      Stereological estimation of the sperm tail length, including sampling of
      spermatozoa and also counting of the intersections of their tails with the
      stereological grids was a rapid technique and took only 5-10 minutes. It can be
      concluded that curcumin has an ameliorative effect on the spermatozoon,
      testosterone level and tail length in MTZ-treated mice.

PMID- 22142525
TI  - Black mamba dendroaspis polylepis bite: a case report.
AB  - Although very rare in a European context, a bite from the black mamba Dendroaspis
      polylepis is an event that poses an immediate threat to life. Given the content
      of neurotoxins in the snake's venom, the mortality of envenomation reaches 100%
      in almost every case if ventilation is not provided in a timely manner and
      adequate therapy initiated. The report describes a case of a snake breeder being
      envenomed. This 31-year-old man was bitten by a black mamba on his finger, and
      who subsequently developed clinical symptoms of envenoming typical for the
      species. Thanks to mechanical ventilation being employed promptly, with
      myorelaxation during generalized muscle fasciculations, and particularly owing to
      the eventual antivenin therapy, the patient's condition settled without
      consequences. In addition to describing the given case in detail, the paper
      discusses the composition and mechanisms of action of black mamba venom, while
      providing guidelines for adequate therapy.

PMID- 22142526
TI  - Adolescent patient with bilateral crossbite treated with surgically assisted
      rapid maxillary expansion: a case report evaluated by the 3d laser scanner, and
      using FESA method.
AB  - Our purpose in this case report is to present an orthodontic treatment obtained
      and the results achieved in 17-year-old white female patient with Angle Class II
      malocclusion and bilateral posterior crossbite. Patient was treated with bonded
      acrylic Hyrax appliance and surgically assisted rapid maxillary expansion
      (SARME). The multiloop system 0.16 TMA (beta titanium) arch wire was used in the
      alignment phase and on purpose to prohibit bite opening and optimize
      threedimensional movement control. After treatment bonded lingual retainers were
      placed in between maxillary central incisors and in mandible canine-to-canine. A
      functional removable Klammt appliance was used for retention. The 3D Laser
      Scanner Roland LPX-250 was used in order to obtain digital dental casts.
      Evaluation of the treatment results was measured on these models and using finite
      element scaling analysis (FESA). An Angle Class I relationship was obtained after
      21/2 years of treatment, function and facial aesthetics were improved. The shape
      of the palate changed significant in the width direction, not significantly in
      length and high direction. The greatest expansion of palate was found in the
      region between the palatal cusps of the first molars 26.6%, followed by first
      21.9% and second premolars 16.5%. SARME in adult patients with bilateral cross
      bite and maxillary deficiency lead to satisfactory results. The 3D laser scanned
      models and their measurements, using advanced software's are successfully used
      for precise studies.

PMID- 22142527
TI  - Laparoscopic mesh repair of parastomal hernia. Is it a sufficient and free of
      complication technique? a case presentation and review of the literature.
AB  - Parastomal hernia is a complication of stoma formation. It is accompanied by high
      morbidity. It affects stoma's function and patient's quality of life. There
      several alternative treatment options including stoma relocation, primary
      prophylactic repair during the stoma construction and open or laparoscopic mesh
      repair. We describe the case of a young woman with Crohn's disease that presented
      a parastomal hernia at the site of an ileostomy. We performed a laparoscopic mesh
      placement and repair of the hernia. After 28 months of follow-up, the patient
      remains complications and recurrence-free. The laparoscopic mesh repair is a
      challenging way to treat parastomal hernias. In the studies have been done so far
      comparing this approach with the other alternative treatments, the laparoscopic
      way seems to offer remarkable therapeutic results with minor complication and
      recurrence rates. Our department's experience is suggesting that laparoscopic
      repair is an effective and sufficient treatment option.

PMID- 22142528
TI  - Spontaneous left main coronary artery dissection in pregnancy.

PMID- 22142529
TI  - Use of thrombectomy devices in primary percutaneous coronary intervention: a
      systematic review and meta-analysis.
AB  - AIMS: Primary percutaneous coronary intervention (PPCI) has become the treatment
      of choice in patients with ST-elevation myocardial infarction (STEMI) over the
      recent years. A number of studies have demonstrated a morbidity and mortality
      benefit over thrombolysis, which has been attributed to better coronary perfusion
      in patients undergoing PPCI. However although PPCI usually achieves normal flow
      in the affected epicardial vessel, myocardial reperfusion is not fully restored
      in a significant percentage of patients. This is commonly the result of distal
      thrombus embolization with subsequent impairment of myocardial microcirculation.
      Recognition of this has led to the development of a number of devices with
      different mechanisms of action that aim to reduce such distal embolization and
      therefore improve end myocardial perfusion. Recent studies indeed demonstrate
      that the use of such devices offer additional clinical advantage in patients
      undergoing PPCI compared to the current practice. This report focuses on
      thrombectomy devices and reviews the evidence that advocates their routine use in
      PPCI patients. METHODS AND RESULTS: We have performed a systematic review of
      currently available thrombectomy devices. We also performed a literature search,
      using the terms "thrombectomy" and "thrombus aspiration" in PubMed and EMBASE.
      Thrombectomy devices were divided in "manual" and "non-manual" groups. We
      performed a meta-analysis of the available randomized control trials that
      compared adjunctive thrombectomy in PPCI to standard PPCI. The use of manual
      thrombectomy devices is associated with significant improvements in ST-segment
      resolution (STR) (p<0.00001), Myocardial Blush Grade (MBG) 3 (p<0.00001),
      Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow (p=0.01) as well as
      clinical parameters (43% reduction in mortality, p=0.04) in patients undergoing
      PPCI. CONCLUSION: Current evidence advocates the routine use of manual
      thrombectomy devices in PPCI. Non-manual (mechanical) thrombectomy may have a
      role in selected PPCI patients with large caliber vessels and heavy thrombus
      burden although their routine use is not presently supported.

PMID- 22142530
TI  - Tamoxifen depresses glutamate release through inhibition of voltage-dependent
      Ca2+ entry and protein kinase Calpha in rat cerebral cortex nerve terminals.
AB  - This study was aimed at examining the effect of tamoxifen, a selective estrogen
      receptor modulator, on the release of endogenous glutamate in rat cerebral cortex
      nerve terminals (synaptosomes) and exploring the possible mechanism. Tamoxifen
      inhibited the release of glutamate that was evoked by the K(+) channel blocker 4
      aminopyridine (4-AP), and this phenomenon was concentration-dependent and
      insensitive to the estrogen receptor antagonist. The effect of tamoxifen on the
      evoked glutamate release was prevented by the chelating extracellular Ca(2+)
      ions, and by the vesicular transporter inhibitor bafilomycin A1. However, the
      glutamate transporter inhibitor dl-threo-beta-benzyloxyaspartate did not have any
      effect on the action of tamoxifen. Tamoxifen did not alter the resting
      synaptosomal membrane potential or 4-AP-mediated depolarization whereas it
      decreased the 4-AP-induced increase in cytosolic [Ca(2+)]. Furthermore, the
      inhibitory effect of tamoxifen on the evoked glutamate release was abolished by
      the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channel blocker omega-conotoxin
      MVIIC, but not by the ryanodine receptor blocker dantrolene, or the mitochondrial
      Na(+)/Ca(2+) exchanger blocker CGP37157. In addition, the protein kinase C (PKC)
      inhibitors GF109203X or Ro318220 prevented tamoxifen from inhibiting glutamate
      release. Western blotting showed that tamoxifen significantly decreased the 4-AP
      induced phosphorylation of PKC and PKCalpha. Together, these results suggest that
      tamoxifen inhibits glutamate release from rat cortical synaptosomes, through the
      suppression of presynaptic voltage-dependent Ca(2+) entry and PKC activity.

PMID- 22142531
TI  - (S)-ZJM-289, a nitric oxide-releasing derivative of 3-n-butylphthalide, protects
      against ischemic neuronal injury by attenuating mitochondrial dysfunction and
      associated cell death.
AB  - Pharmacological compounds that release nitric oxide (NO) have been recognized as
      the potential therapeutic agents for acute stroke. (S)-ZJM-289 is a novel NO
      releasing derivative of 3-n-butylphthalide (NBP) with enhanced anti-platelet and
      anti-thrombotic actions. The present study was performed to investigate the
      neuroprotective effects and related mechanisms of (S)-ZJM-289 on ischemic
      neuronal injury in vitro and in vivo. Primary cortical neuronal cultures were
      exposured to oxygen-glucose deprivation followed by recovery (OGD/R), a model of
      ischemia-like injury, and treated with (S)-ZJM-289 before OGD. In vitro results
      showed that (S)-ZJM-289 attenuated OGD/R-induced neuronal injury, which was
      associated with the maintenance of mitochondrial integrity and function by
      alleviating intracellular calcium overload and reactive oxygen species (ROS)
      accumulation, preventing mitochondrial membrane depolarization and preserving
      respiratory chain complexes activities. Moreover, (S)-ZJM-289 treatment
      suppressed mitochondrial release of cytochrome c (cyt c) and nuclear
      translocation of apoptosis-inducing factor (AIF), thereby blocking mitochondria
      mediated cell death, which may be partially mediated by up-regulation of Hsp70.
      The neuroprotection by (S)-ZJM-289 was also studied using a model of middle
      cerebral artery occlusion (MCAO). Oral administration of (S)-ZJM-289 at the onset
      of reperfusion for 3d significantly reduced the brain infarct size, improved
      neurological deficit and prevented neuronal loss and apoptosis. In current study,
      (S)-ZJM-289 appears to be more potent in ischemic neuroprotection than NBP, in
      particular at the lower doses, which may be due to the synergistic action of NBP
      and NO. These findings point to that (S)-ZJM-289 could be an attractive
      alternative to NBP in preventing the process of ischemia/reperfusion (I/R)
      injury.

PMID- 22142532
TI  - The Netherlands study of depression in older persons (NESDO); a prospective
      cohort study.
AB  - BACKGROUND: To study late-life depression and its unfavourable course and co
      morbidities in The Netherlands. METHODS: We designed the Netherlands Study of
      Depression in Older Persons (NESDO), a multi-site naturalistic prospective cohort
      study which makes it possible to examine the determinants, the course and the
      consequences of depressive disorders in older persons over a period of six years,
      and to compare these with those of depression earlier in adulthood. RESULTS: From
      2007 until 2010, the NESDO consortium has recruited 510 depressed and non
      depressed older persons (>= 60 years) at 5 locations throughout the Netherlands.
      Depressed persons were recruited from both mental health care institutes and
      general practices in order to include persons with late-life depression in
      various developmental and severity stages. Non-depressed persons were recruited
      from general practices. The baseline assessment included written questionnaires,
      interviews, a medical examination, cognitive tests and collection of blood and
      saliva samples. Information was gathered about mental health outcomes and
      demographic, psychosocial, biological, cognitive and genetic determinants. The
      baseline NESDO sample consists of 378 depressed (according to DSM-IV criteria)
      and 132 non-depressed persons aged 60 through 93 years. 95% had a major
      depression and 26.5% had dysthymia. Mean age of onset of the depressive disorder
      was around 49 year. For 33.1% of the depressed persons it was their first
      episode. 41.0% of the depressed persons had a co morbid anxiety disorder. Follow
      up assessments are currently going on with 6 monthly written questionnaires and
      face-to-face interviews after 2 and 6 years. CONCLUSIONS: The NESDO sample offers
      the opportunity to study the neurobiological, psychosocial and physical
      determinants of depression and its long-term course in older persons. Since
      largely similar measures were used as in the Netherlands Study of Depression and
      Anxiety (NESDA; age range 18-65 years), data can be pooled thus creating a large
      longitudinal database of clinically depressed persons with adequate power and a
      large set of neurobiological, psychosocial and physical variables from both
      younger and older depressed persons.

PMID- 22142533
TI  - Public health and valorization of genome-based technologies: a new model.
AB  - BACKGROUND: The success rate of timely translation of genome-based technologies
      to commercially feasible products/services with applicability in health care
      systems is significantly low. We identified both industry and scientists neglect
      health policy aspects when commercializing their technology, more specifically,
      Public Health Assessment Tools (PHAT) and early on involvement of decision makers
      through which market authorization and reimbursements are dependent. While
      Technology Transfer (TT) aims to facilitate translation of ideas into products,
      Health Technology Assessment, one component of PHAT, for example, facilitates
      translation of products/processes into healthcare services and eventually comes
      up with recommendations for decision makers. We aim to propose a new model of
      valorization to optimize integration of genome-based technologies into the
      healthcare system. METHODS: The method used to develop our model is an adapted
      version of the Fish Trap Model and the Basic Design Cycle. RESULTS: We found
      although different, similarities exist between TT and PHAT. Realizing the
      potential of being mutually beneficial justified our proposal of their relative
      parallel initiation. We observed that the Public Health Genomics Wheel should be
      included in this relative parallel activity to ensure all societal/policy aspects
      are dealt with preemptively by both stakeholders. On further analysis, we found
      out this whole process is dependent on the Value of Information. As a result, we
      present our LAL (Learning Adapting Leveling) model which proposes, based on
      market demand; TT and PHAT by consultation/bi-lateral communication should
      advocate for relevant technologies. This can be achieved by public-private
      partnerships (PPPs). These widely defined PPPs create the innovation network
      which is a developing, consultative/collaborative-networking platform between TT
      and PHAT. This network has iterations and requires learning, assimilating and
      using knowledge developed and is called absorption capacity. We hypothesize that
      the higher absorption capacity, higher success possibility. Our model however
      does not address the phasing out of technology although we believe the same model
      can be used to simultaneously phase out a technology. CONCLUSIONS: This model
      proposes to facilitate optimization/decrease the timeframe of integration in
      healthcare. It also helps industry and researchers to come to a strategic
      decision at an early stage, about technology being developed thus, saving on
      resources, hence minimizing failures.

PMID- 22142534
TI  - Subfunctionalization of POMC paralogues in Senegalese sole (Solea senegalensis).
AB  - The precursor protein proopiomelanocortin (POMC) gives rise to a variety of
      biologically active peptides through cell-specific posttranslational processing.
      Two transcripts of pomc were found in the flatfish Solea senegalensis (ssePOMC-A
      and ssePOMC-B), that most likely represent subfunctionalized paralogues: ssePOMC
      A lacks the N-terminal cleavage site for beta-MSH, whereas ssePOMC-B cannot yield
      ACTH and completely lacks the opioid consensus sequence in the beta-END region.
      An analysis of nucleotide substitution rates shows that the POMC-derived peptides
      possess well-conserved regions under purifying selection, except the beta-END
      derived from POMC-B, which has undergone positive selection. The calculated K(s)
      values for ssePOMC-A versus ssePOMC-B and zebrafish POMCalphaversus zebrafish
      POMCbeta are 0.40 and 0.72, respectively, indicating that the zebrafish POMC
      paralogues started to evolve almost twice as early in evolution, and that the
      Solea POMC paralogues arose independently from the whole genome duplication event
      that gave rise to the zebrafish paralogues. This makes ssePOMC-B the first
      identified POMCalpha orthologue that lacks the opioid consensus. Furthermore,
      pomc-a expression is down-regulated in chronic stressed S. senegalensis
      juveniles, whereas pomc-b expression levels remain unaffected, indicating
      different physiological roles for both POMC paralogues. The distribution of
      functional POMC-derived peptide hormones over two pomc genes in S. senegalensis
      suggests subfunctionalization of the paralogues, a relevant notion when studying
      POMC function in endocrine responses.

PMID- 22142535
TI  - Local expression and distribution of growth hormone and growth hormone receptor
      in the chicken ovary: effects of GH on steroidogenesis in cultured follicular
      granulosa cells.
AB  - Preovulatory follicular development (PFD) is mainly regulated by gonadotropins
      (FSH, LH) and steroids, although other intraovarian factors are also involved. We
      analyzed the local expression of growth hormone (GH) in the hen ovary and the
      role that this hormone may play on the regulation of steroidogenesis in granulosa
      cells (GCs). Ovarian follicles from sexually mature hens were studied at
      different developmental stages. Both GH mRNA (by in situ hybridization) and
      protein (by immunohistochemistry) were expressed mainly in the GCs, and to a
      lesser extent in the theca cells of the follicular wall. Sequence of a GH cDNA
      690-bp fragment obtained from the follicular wall was identical to that obtained
      from the pituitary. The growth hormone receptor (GHR) mRNA was also expressed in
      the follicles. Nine GH variants were observed by SDS-PAGE and Western blotting,
      but the main isoform showed a MW of 17 kDa, at all developmental stages. Addition
      of GH (0.1, 1, 10 nM) stimulated the synthesis of progesterone (P4) in primary
      GCs cultures in a dose-dependent manner (1.5, 2.9, 5.4 times, respectively). GH
      also stimulated the expression of cholesterol side-chain cleavage enzyme
      (cytochrome P450scc) mRNA, a rate-limiting enzyme during P4 synthesis (2.9, 4.6,
      4.9 times, respectively), whereas the synthesis of 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) mRNA (a constitutive enzyme) was not changed. Both GH
      and GHR were co-expressed in GCs cultures. The locally expressed GH present in
      concentrated (4*, 6*, 8*) conditioned media obtained from ovarian GC cultures
      stimulated P4 production (1.2, 2.2, 4.4 times, respectively) in additional fresh
      cultured GCs, and this effect disappeared when the conditioned media were treated
      with antiserum against GH. These data suggest that locally produced GH may
      modulate follicular development through autocrine/paracrine effects in the
      chicken ovary.

PMID- 22142536
TI  - The sporulation control gene spo0M of Bacillus subtilis is a target of the FtsH
      metalloprotease.
AB  - In an attempt to identify substrate proteins of the FtsH metalloprotease involved
      in stage 0 of sporulation in Bacillus subtilis, the proteome of an ftsH wild-type
      strain was compared to that of an ftsH null mutant by the 2D gel technique. One
      of the most abundant proteins identified in the absence of ftsH turned out to be
      Spo0M, a sporulation control protein of stage 0. Using transcriptional fusion
      between the spo0M promoter and the bgaB reporter gene, expression analysis did
      not reveal any influence of FtsH on spo0M transcription, suggesting that FtsH
      might have a negative effect on the stability of Spo0M due to its proteolytic
      activity on Spo0M. Indeed, in vitro incubation of purified components
      demonstrated that Spo0M was degraded by FtsH, indicating that it serves as a
      substrate for the FtsH protease. These results are discussed.

PMID- 22142537
TI  - Skin hardening effect in patients with polymorphic light eruption: comparison of
      UVB hardening in hospital with a novel home UV-hardening device.
AB  - BACKGROUND: An effective prophylactic treatment of patients with polymorphic
      light eruption (PLE) consists of repeated low, gradually increasing exposures to
      UVB radiation. This so-called UV(B) hardening induces better tolerance of the
      skin to sunlight. OBJECTIVE: SunshowerMedical company (Amsterdam) has developed
      an UV (B) source that can be used during taking shower. The low UV fluence of
      this apparatus makes it an interesting device for UV hardening. In a group of PLE
      patients, we compared the effectiveness of the irradiation with SunshowerMedical
      at home with that of the UVB treatment in the hospital. METHODS: The PLE patients
      were randomized for one of the treatments. The hospital treatment consisted of
      irradiations with broad-band UVB (Waldmann 85/UV21 lamps) twice a week during 6
      weeks. The home UV-device was used each day with the maximal irradiation time of
      6 min. The outcome assessment was based on the information obtained from
      patients' dermatological quality of life (DLQI) questionnaires, the ability of
      both phototherapies to reduce the provocation reaction and from the patients'
      evaluation of the long-term benefits of their phototherapies. RESULTS: Sixteen
      patients completed treatment with SunshowerMedical and thirteen completed
      treatment in hospital. Both types of phototherapy were effective. There was a
      highly significant improvement in DLQI with either treatment. In most cases, the
      hardening reduced or even completely suppressed clinical UV provocation of PLE.
      The patients using SunshowerMedical at home were, however, much more content with
      the treatment procedure than the patients visiting the dermatological units.
      CONCLUSIONS: Both treatments were equally effective in the induction of skin
      tolerance to sunlight in PLE patients. However, the home treatment was much
      better accepted than the treatment in the hospital.

PMID- 22142538
TI  - Antiangiogenic activity of 3,4-seco-cycloartane triterpenes from Thai Gardenia
      spp. and their semi-synthetic analogs.
AB  - Twelve naturally occurring 3,4-seco-cycloartane triterpenes (1-12) isolated from
      Gardenia sootepensis and Gardenia obtusifolia, and eight semi-synthetic
      derivatives (13-20) were evaluated for their antiangiogenic activity on a rat
      aortic sprouting assay, an ex vivo model of angiogenesis. Among these compounds,
      sootepin B (1) displayed the most potent activity in terms of the inhibition of
      microvessel sprouting from rat aortic rings in a dose-dependent manner with
      IC(50) value of 4.46 MUM. Its angiogenic effect was found to occur via
      suppression of endothelial cell proliferation and tubular formation, and was
      likely mediated by regulation (inhibition) of the Erk1/2 signaling pathway.

PMID- 22142539
TI  - An expedient synthesis of honokiol and its analogues as potential neuropreventive
      agents.
AB  - An efficient synthesis of honokiol with Suzuki-Miyaura cross coupling obtained an
      overall yield of 45%. The proposed approach successfully synthesized several
      structurally similar alkyl, alkenyl and alkynyl analogues, seven of which showed
      potential neuropreventive activity against MPP(+)-induced and CHP/TBHP oxidative
      stress induced neuroblastoma cell death.

PMID- 22142540
TI  - Synthesis of bivalent lactosides and their activity as sensors for differences
      between lectins in inter- and intrafamily comparisons.
AB  - The synthesis of nine bivalent lactosides (based on ditriazoles, diamides, a
      glycocyclophane and an acyclic analogue of the glycocyclophane) and one
      monovalent lactosyl triazole facilitated the assessment of the sensitivity of
      plant/animal lectins to this type of ligand display. The inhibitory potency of
      the compounds was determined in two assays of increasing biorelevance. These were
      solid-phase and cell binding set-ups. Hereby, the ability of the compounds to
      inhibit the binding of two plant agglutinins and the entire set of
      adhesion/growth-regulatory galectins from one organism (chicken) to a
      glycoprotein or to cell surfaces was systematically evaluated. Differential
      sensitivities were detected between plant and animal lectins and also between
      distinct galectin forms within the chicken series. Two of the bivalent probes can
      be considered as sensors for interlectin differences. Most pronounced were the
      selectivities of N-glycosyl 1,2,3-triazole derivatives for the chimera-type
      galectin and its proteolytically truncated version.

PMID- 22142541
TI  - SAR studies on the central phenyl ring of substituted biphenyl oxazolidinone
      potent CETP inhibitors.
AB  - SAR studies of the substitution effect on the central phenyl ring of the biphenyl
      scaffold were carried out using anacetrapib (9a) as the benchmark. The results
      revealed that the new analogs with substitutions to replace trifluoromethyl (9a)
      had a significant impact on CETP inhibition in vitro. In fact, analogs with some
      small groups were as potent or more potent than the CF(3) derivative for CETP
      inhibition. Five of these new analogs raised HDL-C significantly (>20mg/dL). None
      of them however was better than anacetrapib in vivo. The synthesis and biological
      evaluation of these CETP inhibitors are described.

PMID- 22142542
TI  - 4,5-dihydropyridazin-3-one derivatives as histamine H3 receptor inverse agonists.
AB  - H(3)R structure-activity relationships for a new class of 4,5-dihydropyridazin-3
      one H(3)R antagonists/inverse agonists are disclosed. Modification of the 4,5
      dihydropyridazinone moiety to block in vivo metabolism identified 4,4-dimethyl-6
      {4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-4,5-dihydro-2H-pyridazin-3
      one 22 as a lead candidate demonstrating potent in vivo functional H(3)R
      antagonism in the rat dipsogenia model and robust wake promoting activity in the
      rat EEG/EMG model.

PMID- 22142544
TI  - Synthesis of dihydrofuran-fused perhydrophenanthrenes having a phenolic hydroxyl
      group as a novel anti-Alzheimer's disease agent.
AB  - As a part of our research program on developing novel anti-Alzheimer's disease
      medicines, several dihydrofuran-fused perhydrophenanthrenes (DFs) possessing a
      phenolic hydroxyl group were found to exhibit potent dendritic and axonal
      regeneration activities. Introduction of a methoxy group into the
      perhydrophenanthrene skeleton was successfully achieved via a PhI(OAc)(2)
      mediated phenolic oxidation of a benzocyclobutene nucleus and subsequent tandem
      intramolecular electrocyclic reactions based on o-quinodimethane chemistry. We
      could reveal that a new methoxy derivative having a phenolic hydroxyl group
      exerted the most significant effects on the dendritic and axonal extensions in
      the damaged neurons, among DFs examined in this study.

PMID- 22142543
TI  - Cytotoxic esterified diterpenoid alkaloid derivatives with increased selectivity
      against a drug-resistant cancer cell line.
AB  - C-6 Esterifications of delpheline (1) were carried out to provide 20 new
      diterpenoid alkaloid derivatives (4-22, 24). Three natural alkaloids (1-3) and
      all synthesized compounds (4-25) were evaluated for cytotoxic activity against
      lung (A549), prostate (DU145), nasopharyngeal (KB), and vincristine-resistant
      nasopharyngeal (KB-VIN) cancer cell lines and interestingly, showed an improved
      drug resistance profile compared to paclitaxel. Particularly, 6-(4-fluoro-3
      methylbenzoyl)delpheline (22) displayed 2.6-fold greater potency against KB-VIN
      cells compared with the parental non-drug resistant KB cells. 6-Acylation of 1
      appears to be critical for producing cytotoxic activity in this alkaloid class
      and a means to provide promising new leads for further development into antitumor
      agents.

PMID- 22142545
TI  - Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the
      management of schizophrenia.
AB  - A series of pyrazoloquinoline analogs have been synthesized and shown to bind to
      PDE10 with high affinity. From the SAR study and our lead optimization efforts,
      compounds 16 and 27 were found to possess potent oral antipsychotic activity in
      the MK-801 induced hyperactive rat model.

PMID- 22142547
TI  - Geoepidemiology, gender and autoimmune disease.
AB  - Autoimmune diseases include more than 70 different disorders affecting over 5% of
      the population of the Western countries. They are mainly characterized by female
      predominance and have great impact on the quality of life of affected subjects.
      It is generally accepted that ADs are the result of a complex interaction between
      genetic and environmental factors; however the mechanisms involved in the loss of
      tolerance remain unknown. Studying the distribution of these conditions across
      various global regions and ethnic groups by means of geoepidemiology might
      readily provide epidemiological data and also advance our understanding of their
      pathogenesis. Indeed, geoepidemiology demonstrates that genetic susceptibility
      interacts with lifestyle and environmental factors, which include socioeconomic
      status, infectious agents (triggering or protective agents), environmental
      pollutants, and vitamin D (dependent on sunlight exposure), in determining the
      risk of developing autoimmunity and in the understanding of their female
      prevalence. To properly understand the geoepidemiology of human autoimmunity, it
      is important to consider the many pleiotropic factors which lead to its
      initiation. In most studies the focus has been on genetics and environment.
      However, in this review the focus is primarily on gender. Overall, autoimmune
      diseases are well known to have female predominance, but there is significant
      variation in geographic area. Further, the mechanisms that influence female
      predominance are relatively unknown. Hence the attempt in this review is to focus
      on these critical issues.

PMID- 22142546
TI  - AChE inhibitor: a regio- and stereo-selective 1,3-dipolar cycloaddition for the
      synthesis of novel substituted 5,6-dimethoxy spiro[5.3']-oxindole-spiro-[6.3"]
      2,3-dihydro-1H-inden-1"-one-7-(substituted aryl)-tetrahydro-1H-pyrrolo[1,2
      c][1,3]thiazole.
AB  - Pyrrolothiazolyloxindole analogues share vital pharmacological properties,
      considered useful in Alzheimer's disease (AD). The aim of this study was
      synthesis and evaluate pyralothiazolyloxindole analogues if possess acetyl
      cholinesterase (AChE) inhibitory activity. The easily accessible one-pot
      synthesis of these compounds resulted to be significantly less difficult and
      expensive than that of donepezil. Several compounds possess anti-cholinesterase
      activity in the order of micro and sub-micromolar. Particularly, compound was the
      most potent inhibitors of the series against acetyl cholinesterase enzyme with
      IC(50) 0.11MUmol/L.

PMID- 22142548
TI  - Preservation of nutritional-status in patients with refractory ascites due to
      hepatic cirrhosis who are undergoing repeated paracentesis.
AB  - BACKGROUND AND AIM: Refractory ascites in liver-cirrhosis is associated with a
      poor prognosis. We performed a prospective study to investigate whether
      aggressive nutritional-support could improve outcomes in cirrhotic patients.
      METHODS: Cirrhotic patients undergoing serial large-volume paracentesis for
      refractory-ascites were enrolled and randomized into three groups. Group A
      received post-paracentesis intravenous nutritional-support in addition to a
      balanced oral diet and a late-evening protein snack, group B received the same
      oral nutritional-protocol as the first group but without parenteral support, and
      group C (the control group) received a low-sodium or sodium-free diet. Clinical,
      anthropometric and laboratory nutritional parameters and biochemical tests of
      liver and renal function were reported for 12 months of follow-up. RESULTS: We
      enrolled 120 patients, who were randomized into three groups of equal size.
      Patients on the nutritional-protocol showed better preservation of clinical,
      anthropometric and laboratory nutritional parameters that were associated with
      decreased deterioration of liver function compared with patients on the low
      sodium or sodium-free diet (group C). Groups A and B had lower morbidity and
      mortality rates than the control group (C). Mortality rates were significantly
      better in patients who were treated with parenteral-nutritional-support than for
      the other two groups. In patients who were on the nutritional-protocol, there was
      a reduction in the requirement of taps for the treatment of refractory ascites.
      CONCLUSIONS: Post-paracentesis parenteral-nutritional-support with a balanced
      oral diet and an evening protein snack appears to be the best care protocol for
      patients with liver-cirrhosis that has been complicated by refractory-ascites.

PMID- 22142549
TI  - Clear-cell papulosis: a rare entity that may be misconstrued pathologically as
      normal skin.
AB  - We describe a case of multiple, discrete, hypopigmented macules in the suprapubic
      and axillary region in a healthy 3-year-old girl. The lesions first appeared at
      approximately 9 months of age and increased in number over time. Initial
      histopathologic examination by an outside dermatopathologist at 1 year of age was
      reported as showing nonspecific histologic changes. A repeat biopsy at 3 years of
      age showed large intraepidermal clear cells that expressed CKAE1/CAM5.2, CK7, and
      BRST2. These findings are diagnostic for clear-cell papulosis, a rare condition
      that primarily affects children. Without great clinical and pathologic suspicion,
      this is a diagnosis that can often be overlooked because the histologic findings
      are virtually identical to those of normal skin.

PMID- 22142550
TI  - The neuropsychology of prefrontal function in antisocial personality disordered
      offenders with varying degrees of psychopathy.
AB  - BACKGROUND: Despite methodological differences between studies, it has been
      suggested that psychopathy may be associated with a ventromedial prefrontal
      cortex (VMPFC) deficit and antisocial personality disorder (ASPD), as classified
      in the DSM-IV, with a broader range of deficits in dorsolateral prefrontal cortex
      (DLPFC) and VMPFC function. METHOD: Ninety-six male offenders with ASPD who were
      assessed using the psychopathy checklist: screening version (PCL:SV) and 49 male
      right-handed healthy controls (HCs), matched for age and IQ, completed a
      neuropsychological test battery. RESULTS: Offenders with ASPD displayed subtle
      impairments on executive function tasks of planning ability and set shifting and
      behavioural inhibition compared to HCs. However, among the offenders with ASPD
      there was no significant association between executive function impairment and
      scores on the measure of psychopathy. CONCLUSIONS: Psychopathic traits in
      offenders with ASPD are not associated with greater executive function
      impairment.

PMID- 22142552
TI  - Getting published in peer-reviewed journals.
AB  - Writing a paper for publication in a peer-reviewed journal is a rewarding
      experience but a very difficult undertaking that requires years of experience,
      determination and patience. The exponential rise of knowledge has resulted in the
      exponential rise of manuscripts submitted for publication in the various peer
      reviewed journals all over the world. Potential authors are not only having to
      write high-quality papers to get published, but also have to compete with other
      authors for the limited journal space available to publish their papers. The
      purpose of this article is to highlight some of the ways of making the task of
      getting published in peer-reviewed journals easier to achieve.

PMID- 22142553
TI  - Palladium-catalyzed arylation of cyanamides.
AB  - The cross-coupling of alkyl cyanamides with a number of aryl, heteroaryl, and
      vinyl halide and pseudohalide coupling partners has been developed via a
      modification of Pd-catalyzed amidation methods. The reactions proceed selectively
      under mild conditions with reasonable reaction times in moderate to excellent
      yields.

PMID- 22142554
TI  - A systematic review and economic evaluation of cilostazol, naftidrofuryl oxalate,
      pentoxifylline and inositol nicotinate for the treatment of intermittent
      claudication in people with peripheral arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a condition in which there is
      blockage or narrowing of the arteries that carry blood to the legs and arms. It
      is estimated to affect around 4.5% of people aged between 55 and 74 years within
      the UK. The most common symptom of PAD is intermittent claudication (IC),
      characterised by pain in the legs on walking that is relieved with rest.
      OBJECTIVE: To assess the effectiveness and cost-effectiveness of cilostazol,
      naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no
      vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a
      period of conventional management. DATA SOURCE: Electronic bibliographic
      databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process &
      Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative
      Index to Nursing and Allied Health Literature, Web of Science, Conference
      Proceedings Citation Index, BIOSIS Previews). REVIEW METHODS: Effectiveness
      outcomes sought were maximal walking distance (MWD), pain-free walking distance
      (PFWD), ankle-brachial pressure index, cardiovascular events, mortality, adverse
      events (AEs) and health-related quality of life (HRQoL). A narrative synthesis
      was provided for all outcomes and a network meta-analysis was undertaken for the
      walking distance outcomes. A Markov model was developed to assess the relative
      cost-effectiveness of the interventions from a NHS perspective over a lifetime.
      The model has three states: vasoactive drug treatment, no vasoactive drug
      treatment and death. Each 1-week cycle, patients may continue with the drug,
      discontinue the drug or die. Regression analysis was undertaken to model the
      relationship between MWD and utility so that a cost per quality-adjusted life
      year (QALY) outcome measure could be presented. Univariate and probabilistic
      sensitivity analyses were undertaken. All costs and outcomes were discounted at
      3.5%. RESULTS: Twenty-six randomised controlled trials were identified that met
      the inclusion criteria for the clinical effectiveness review. There was evidence
      that walking distance outcomes were significantly improved by both cilostazol and
      naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo
      in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to
      0.762, respectively. It was not possible to include inositol nicotinate within
      the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however,
      the shorter-term data did not suggest a significant effect. AEs were minor for
      all drugs and included headaches and gastrointestinal difficulties. The incidence
      of serious adverse events (SAEs), including cardiovascular events and mortality,
      was not increased by the vasoactive drugs compared with placebo; however, most
      studies had a relatively short follow-up time to address this outcome. HRQoL data
      were limited. Two studies of limited quality were identified within the review of
      cost-effectiveness. The de novo model developed suggests that naftidrofuryl
      oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of
      around L6070 compared with no vasoactive drug. This result is reasonably robust
      to changes within the key model assumptions. Inositol nicotinate was not included
      within the main analysis owing to lack of data. However, it is unlikely to be
      considered to be cost-effective due to its high acquisition cost (L900 vs L100
      500 per year for the other drugs). CONCLUSIONS: Naftidrofuryl oxalate and
      cilostazol both appear to be effective treatments for this patient population,
      with minimal SAEs. However, naftidrofuryl oxalate is the only treatment that is
      likely to be considered cost-effective. The long-term effectiveness is uncertain
      and hence a trial comparing cilostazol, naftidrofuryl oxalate and placebo beyond
      24 weeks would be beneficial. Outcomes associated with naftidrofuryl oxalate
      could also be compared with those associated with supervised exercise programmes
      and angioplasty.

PMID- 22142555
TI  - Strong association of phenylalanine and tryptophan metabolites with activated
      cytomegalovirus infection in kidney transplant recipients.
AB  - Infection-induced inflammation triggers catabolism of proteins and amino acids.
      Phenylalanine and tryptophan are 2 amino acids related to infections that
      regulate immune responses. Polyomavirus BK (BKV) and cytomegalovirus (CMV) are
      important pathogens after kidney transplantation. We investigated the clinical
      relevance of phenylalanine, tryptophan, and tryptophan metabolites (kynurenine
      and quinolinic acid) plasma levels in kidney transplant recipients with active
      CMV (BKV(-)CMV(+), n = 12) or BK virus infection (BKV(+)CMV(-), n = 37).
      Recipients without active viral infections (CMV(-)BKV(-), n = 28) and CMV(-)BKV(
      ) healthy individuals (HCs, n = 50) served as controls. In contrast to BKV
      infection, activated CMV infection is tightly linked to increased phenylalanine
      and tryptophan metabolite plasma levels (p <= 0.002). The association of
      phenylalanine (cutoff 50 MUmol/L) with CMV infection demonstrates high
      sensitivity (100%) and specificity (94%). By contrast, kynurenine (p = 0.029) and
      quinolinic acid (p = 0.003) values reflect the severity of CMV infection. In this
      early proof-of-concept trial, evidence indicates that activated CMV infection is
      strongly associated with increased phenylalanine as well as kynurenine and
      quinolinic acid plasma levels. Moreover, tryptophan metabolite levels correlate
      with disease severity. Measurement of these amino acids is an inexpensive and
      fast method expected to complete conventional diagnostic assays.

PMID- 22142556
TI  - Two pediatric cases of Diphyllobothrium nihonkaiense infection in summer (July
      August) 2010.

PMID- 22142557
TI  - A comparison of ARMS and direct sequencing for EGFR mutation analysis and
      tyrosine kinase inhibitors treatment prediction in body fluid samples of non
      small-cell lung cancer patients.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is strongly
      associated with the therapeutic effect of tyrosine kinase inhibitors (TKIs) in
      patients with non-small-cell lung cancer (NSCLC). Nevertheless, tumor tissue that
      needed for mutation analysis is frequently unavailable. Body fluid was considered
      to be a feasible substitute for the analysis, but arising problems in clinical
      practice such as relatively lower mutation rate and poor clinical correlation are
      not yet fully resolved. METHOD: In this study, 50 patients (32 pleural fluids and
      18 plasmas) with TKIs therapy experience and with direct sequencing results were
      selected from 220 patients for further analysis. The EGFR mutation status was re
      evaluated by Amplification Refractory Mutation System (ARMS), and the clinical
      outcomes of TKIs were analyzed retrospectively. RESULTS: As compared with direct
      sequencing, 16 positive and 23 negative patients were confirmed by ARMS, and the
      other 11 former negative patients (6 pleural fluids and 5 plasmas) were redefined
      as positive, with a fairly well clinical outcome (7 PR, 3 SD, and 1 PD). The
      objective response rate (ORR) of positive patients was significant, 81.3% (direct
      sequencing) and 72.7% (ARMS) for pleural fluids, and 80% (ARMS) for plasma.
      Notably, even reclassified by ARMS, the ORR for negative patients was still
      relatively high, 60% for pleural fluids and 46.2% for plasma. CONCLUSIONS: When
      using body fluids for EGFR mutation analysis, positive result is consistently a
      good indicator for TKIs therapy, and the predictive effect was no less than that
      of tumor tissue, no matter what method was employed. However, even reclassified
      by ARMS, the correlation between negative results and clinical outcome of TKIs
      was still unsatisfied. The results indicated that false negative mutation still
      existed, which may be settled by using method with sensitivity to single DNA
      molecule or by optimizing the extraction procedure with RNA or CTC to ensure
      adequate amount of tumor-derived nucleic acid for the test.

PMID- 22142558
TI  - Comparison of intraoperative time use and perioperative outcomes for robotic
      versus laparoscopic adrenalectomy.
AB  - BACKGROUND: Recently, robotic techniques have been described for adrenalectomy.
      However, scant data exist in the literature regarding the comparison of robotic
      with the conventional laparoscopic approach. We aimed to analyze intraoperative
      time use and perioperative outcomes in robotic vs laparoscopic adrenalectomy for
      both lateral transabdominal (LT) and posterior retroperitoneal (PR) approaches.
      METHODS: A robotic adrenalectomy program was started in September 2008, and
      techniques for both the LT (n = 32) and PR (n = 18) approaches were established.
      Data of robotic cases were compared with those of 50 consecutive laparoscopic
      cases (LT = 32, PR = 18) before the onset of the program from a prospective,
      institutional review board-approved database. Operative times for individual
      steps of the procedures were captured from operative video recordings, including
      docking, exposure, dissection, and hemostasis. RESULTS: For both LT and PR
      approaches, there was no difference when we compared the robotic with the
      laparoscopic groups regarding demographics, tumor type, and body mass index. For
      the LT approach, despite larger tumor size (x +/- SEM) in the robotic vs the
      laparoscopic group (4.7 +/- 0.4 vs 3.8 +/- 0.4 cm, P = .05), the operative times
      were similar (168 +/- 10 minutes vs 159 +/- 8 minutes, P = .5). There was no
      difference between the two approaches regarding the time spent for the individual
      steps of the operation. In the PR approach, with similar tumor sizes (2.7 +/- 0.3
      cm vs 2.3 +/- 0.3 cm, P = .4), operative time (minutes) was equivalent (166 +/- 9
      vs 170 +/- 15; P = .8). Time spent intra-operatively for each step was similar,
      except for shorter hemostasis time in the robotic group (23 +/- 4 minutes vs 42
      +/- 9 minutes, P = .03). The robotic docking time (21 vs 25 minutes) decreased by
      50% in the second year of the study for both approaches. The presence of two
      staff surgeons vs a staff and a fellow decreased operative time for the robotic
      LT (P < .02) but not the robotic PR approach. For laparoscopic and robotic
      procedures, the morbidity was 10% and 2%, respectively. Overall, hospital stay
      was 1.5 +/- 0.9 days (range, 1-4 vs 1.1 +/- 0.3 days) (range, 1-2; P = .006). The
      percentage of patients requiring more than 1 day of hospital stay was 28% vs 14%
      (P = .09). CONCLUSION: To our knowledge, this is the first study reporting an
      intraoperative time analysis for robotic adrenalectomy. Intraoperative time use
      was similar between the laparoscopic and robotic groups for both LT and PR
      approaches. However, the morbidity was less and hospital stay was shorter after
      the robotic procedures.

PMID- 22142559
TI  - Fabrication and ultraviolet photoresponse characteristics of ordered SnOx (x ~
      0.87, 1.45, 2) nanopore films.
AB  - Based on the porous anodic aluminum oxide templates, ordered SnOx nanopore films
      (approximately 150 nm thickness) with different x (x ~ 0.87, 1.45, 2) have been
      successfully fabricated by direct current magnetron sputtering and oxidizing
      annealing. Due to the high specific surface area, this ordered nanopore films
      exhibit a great improvement in recovery time compared to thin films for
      ultraviolet (UV) detection. Especially, the ordered SnOx nanopore films with
      lower x reveal higher UV light sensitivity and shorter current recovery time,
      which was explained by the higher concentration of the oxygen vacancies in this
      SnOx films. This work presents a potential candidate material for UV light
      detector.PACS: 81.15.Cd, 81.40.Ef, 81.70.Jb, 85.60.Gz.

PMID- 22142561
TI  - Molecular properties of a venom allergen-like protein suggest a parasitic
      function in the pinewood nematode Bursaphelenchus xylophilus.
AB  - The pinewood nematode, Bursaphelenchus xylophilus, is a destructive pest in
      several countries including Japan, China and Korea. Of three genes encoding the
      venom allergen-like protein in B. xylophilus, Bxvap-1 showed the highest
      transcript levels at the pine-grown propagative stage. In addition, western blot
      and immunohistochemical analyses using anti-BxVap-1 polyclonal antibody verified
      a specific increase in BxVap-1 expression levels at the pine-grown propagative
      stage. Using immunohistochemistry, BxVap-1 was detected around the putative
      oesophageal glands and metacarpus, suggesting that BxVap-1 is secreted into the
      host pine tree and is involved in the parasitic mechanism. To explain the
      parasitic role of BxVap-1, we measured the migration rate inside pine seedlings
      of B. xylophilus either with or without Bxvap-1 knockdown by RNA interference.
      Bxvap-1 knockdown resulted in a significantly lower migration rate in the >6cm
      region compared with the control B. xylophilus. These results suggest that BxVap
      1 is involved in B. xylophilus migration, perhaps by suppressing the pine tree
      defence mechanism.

PMID- 22142562
TI  - When, how and why glycolysis became compartmentalised in the Kinetoplastea. A new
      look at an ancient organelle.
AB  - A characteristic, well-studied feature of the pathogenic protists belonging to
      the family Trypanosomatidae is the compartmentalisation of the major part of the
      glycolytic pathway in peroxisome-like organelles, hence designated glycosomes.
      Such organelles containing glycolytic enzymes appear to be present in all members
      of the Kinetoplastea studied, and have recently also been detected in a
      representative of the Diplonemida, but they are absent from the Euglenida.
      Glycosomes therefore probably originated in a free-living, common ancestor of the
      Kinetoplastea and Diplonemida. The initial sequestering of glycolytic enzymes
      inside peroxisomes may have been the result of a minor mistargeting of proteins,
      as generally observed in eukaryotic cells, followed by preservation and its
      further expansion due to the selective advantage of this specific form of
      metabolic compartmentalisation. This selective advantage may have been a largely
      increased metabolic flexibility, allowing the organisms to adapt more readily and
      efficiently to different environmental conditions. Further evolution of
      glycosomes involved, in different taxonomic lineages, the acquisition of
      additional enzymes and pathways - often participating in core metabolic processes
      - as well as the loss of others. The acquisitions may have been promoted by the
      sharing of cofactors and crucial metabolites between different pathways, thus
      coupling different redox processes and catabolic and anabolic pathways within the
      organelle. A notable loss from the Trypanosomatidae concerned a major part of the
      typical peroxisomal H(2)O(2)-linked metabolism. We propose that the
      compartmentalisation of major parts of the enzyme repertoire involved in energy,
      carbohydrate and lipid metabolism has contributed to the multiple development of
      parasitism, and its elaboration to complicated life cycles involving consecutive
      different hosts, in the protists of the Kinetoplastea clade.

PMID- 22142563
TI  - The senescence accelerated mouse (SAMP8) as a model for oxidative stress and
      Alzheimer's disease.
AB  - The senescence accelerated mouse (SAMP8) is a spontaneous animal model of
      overproduction of amyloid precursor protein (APP) and oxidative damage. It
      develops early memory disturbances and changes in the blood-brain barrier
      resulting in decreased efflux of amyloid-beta protein from the brain. It has a
      marked increase in oxidative stress in the brain. Pharmacological treatments that
      reduce oxidative stress improve memory. Treatments that reduce amyloid-beta
      (antisense to APP and antibodies to amyloid-beta) not only improve memory but
      reduce oxidative stress. Early changes in lipid peroxidative damage favor
      mitochondrial dysfunction as being a trigger for amyloid-beta overproduction in
      this genetically susceptible mouse strain. This sets in motion a cycle where the
      increased amyloid-beta further damages mitochondria. We suggest that this should
      be termed the Inflammatory-Amyloid Cycle and may well be similar to the
      mechanisms responsible for the pathophysiology of Alzheimer's disease. This
      article is part of a Special Issue entitled: Antioxidants and Antioxidant
      Treatment in Disease.

PMID- 22142564
TI  - Multilayer vascular grafts based on collagen-mimetic proteins.
AB  - A major roadblock in the development of an off-the-shelf, small-caliber vascular
      graft is achieving rapid endothelialization of the conduit while minimizing the
      risk of thrombosis, intimal hyperplasia, and mechanical failure. To address this
      need, a collagen-mimetic protein derived from group A Streptococcus, Scl2.28
      (Scl2), was conjugated into a poly(ethylene glycol) (PEG) hydrogel to generate
      bioactive hydrogels that bind to endothelial cells (ECs) and resist platelet
      adhesion. The PEG-Scl2 hydrogel was then reinforced with an electrospun
      polyurethane mesh to achieve suitable biomechanical properties. In the current
      study, initial evaluation of this multilayer design as a potential off-the-shelf
      graft was conducted. First, electrospinning parameters were varied to achieve
      composite burst pressure, compliance, and suture retention strength that matched
      reported values of saphenous vein autografts. Composite stability following
      drying, sterilization, and physiological conditioning under pulsatile flow was
      then demonstrated. Scl2 bioactivity was also maintained after drying and
      sterilization as indicated by EC adhesion and spreading. Evaluation of platelet
      adhesion, aggregation, and activation indicated that PEG-Scl2 hydrogels had
      minimal platelet interactions and thus appear to provide a thromboresistant blood
      contacting layer. Finally, evaluation of EC migration speed demonstrated that PEG
      Scl2 hydrogels promoted higher migration speeds than PEG-collagen analogs and
      that migration speed was readily tuned by altering protein concentration.
      Collectively, these results indicate that this multilayer design warrants further
      investigation and may have the potential to improve on current synthetic options.

PMID- 22142565
TI  - Hepatitis C infection in Italian psoriatic patients: prevalence and correlation
      with patient age and psoriasis severity.

PMID- 22142566
TI  - Patterns of and hypotheses for infection-related cancers in a Chinese population
      with rapid economic development.
AB  - With economic development, non-communicable diseases replace infectious diseases
      as the leading cause of death; how such transition occurs for infectious diseases
      with long latency has rarely been considered. We took advantage of a Chinese
      population with rapid economic development in the mid-20th century to study
      changing patterns of infection-related cancers. We used sex-specific Poisson
      regression to estimate age, period and cohort effects on adult deaths 1976-2005
      from eight infection-related cancers in Hong Kong. Cervical, head and neck, and
      oesophageal cancers, associated with sexually transmitted infections, decreased
      for the first birth cohorts with sexual debut in a more developed environment.
      Leukaemia and non-Hodgkin's lymphoma, associated with vertically transmitted
      infections, decreased for the first cohorts born into a more developed
      environment. Birth cohort patterns were unclear for nasopharyngeal, stomach and
      liver cancers. Mortality rates for cancers related to early infections may depend
      on population history, with delayed reductions for some infection-related
      cancers.

PMID- 22142560
TI  - A comparative transcriptome analysis reveals expression profiles conserved across
      three Eimeria spp. of domestic fowl and associated with multiple developmental
      stages.
AB  - Coccidiosis of the domestic fowl is a worldwide disease caused by seven species
      of protozoan parasites of the genus Eimeria. The genome of the model species,
      Eimeria tenella, presents a complexity of 55-60MB distributed in 14 chromosomes.
      Relatively few studies have been undertaken to unravel the complexity of the
      transcriptome of Eimeria parasites. We report here the generation of more than
      45,000 open reading frame expressed sequence tag (ORESTES) cDNA reads of E.
      tenella, Eimeria maxima and Eimeria acervulina, covering several developmental
      stages: unsporulated oocysts, sporoblastic oocysts, sporulated oocysts,
      sporozoites and second generation merozoites. All reads were assembled to
      constitute gene indices and submitted to a comprehensive functional annotation
      pipeline. In the case of E. tenella, we also incorporated publicly available ESTs
      to generate an integrated body of information. Orthology analyses have identified
      genes conserved across different apicomplexan parasites, as well as genes
      restricted to the genus Eimeria. Digital expression profiles obtained from
      ORESTES/EST countings, submitted to clustering analyses, revealed a high
      conservation pattern across the three Eimeria spp. Distance trees showed that
      unsporulated and sporoblastic oocysts constitute a distinct clade in all species,
      with sporulated oocysts forming a more external branch. This latter stage also
      shows a close relationship with sporozoites, whereas first and second generation
      merozoites are more closely related to each other than to sporozoites. The
      profiles were unambiguously associated with the distinct developmental stages and
      strongly correlated with the order of the stages in the parasite life cycle.
      Finally, we present The Eimeria Transcript Database
      (http://www.coccidia.icb.usp.br/eimeriatdb), a website that provides open access
      to all sequencing data, annotation and comparative analysis. We expect this
      repository to represent a useful resource to the Eimeria scientific community,
      helping to define potential candidates for the development of new strategies to
      control coccidiosis of the domestic fowl.

PMID- 22142567
TI  - Bone marrow cells: Important role on neovascularization of hepatocellular
      carcinoma.
AB  - BACKGROUND AND AIM: Present antivascular therapies including embolization to
      hepatocellular carcinoma (HCC) were not as satisfying as expected. The aim was to
      explore whether or not bone marrow cells (BMCs) played an important role on
      neovascularization in HCC. METHODS: Bone marrow-GFP(+) orthotropic HCC mice model
      was used. In controls and HCC mice, the dynamic change of circulating BMCs and
      serum vascular endothelial growth factor (VEGF), platelet derived growth factor
      (PDGF) were measured by flow cytometry and enzyme linked immunosorbent assay,
      respectively. Intrahepatic distribution of BMCs was evaluated using
      immunofluorescent and realtime polymerase chain reaction protocols. BMCs'
      intrahepatic differentiation and proportion in vessels was investigated by
      immunofluorescent methods. Immunohistochemistry and western blotting were
      performed to examine the expression of adhesion molecule in tumor tissues and
      tumor free tissues. RESULTS: Compared with controls, the frequency of circulating
      BMCs and serum VEGF, PDGF were much higher in HCC mice. The number of BMCs and
      the level of CD133 gene in tumor increased significantly relative to the tumor
      free zone. Since the early stage of HCC, BMCs have been mobilized, recruited into
      tumor and incorporated into different types of vessels of the liver. Besides into
      endothelial cells, BMCs also differentiated into vascular fibroblast and hepatic
      stellate cells. Moreover with tumor growth, the proportion of BMCs in vessels
      increased gradually. CONCLUSION: Mobilized BMCs played an important role in tumor
      vasculogenesis of HCC. Combined blockading of bone marrow-mediated vasculogenesis
      may improve the efficacy of current therapy to HCC patients.

PMID- 22142568
TI  - High morbidity after laparoscopic emergency colectomy for inflammatory bowel
      disease.
AB  - INTRODUCTION: Only limited data are available on subtotal laparoscopic colectomy
      (STC) in patients with in inflammatory bowel disease. We present the first Danish
      experiences with intended laparoscopic STC for inflammatory bowel disease (IBD).
      The primary outcome was 30-day morbidity. MATERIAL AND METHODS: The present study
      is a retrospective single-centre study with consecutive enrolment of patients
      undergoing intended STC for IBD from 1 January 2005 to 31 July 2009. The results
      were analysed as either emergency or elective operations. Only the most severe
      complication was noted for each patient. Data on medical treatment, blood tests
      and complications and death within 30 days were registered. RESULTS: A total of
      32 patients underwent surgery (15 elective and 17 emergency procedures). Patients
      in the emergency group had significantly more severe disease activity than
      elective patients. Severe complications were recorded in 47% and 20% of the
      patients undergoing emergency and elective STC, respectively (p = 0.15). The
      overall morbidity was 72%. One emergency patient died. Five of eight emergency
      patients and one of three elective patients underwent conversion and experienced
      a major complication (p = 0.55). The overall conversion rate was 32% (p = 0.15).
      CONCLUSION: We found high morbidity and conversion rates in patients undergoing
      SLC for IBD. A prospective national Danish survey on early postoperative outcome
      is suggested. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22142569
TI  - Criteria-based emergency medical dispatch of ambulances fulfils goals.
AB  - INTRODUCTION: In Denmark, Alarm 112 (112) calls and emergency medical dispatch
      (EMD) are two separate institutions. 112 calls are mainly answered by the police.
      In Aarhus, a new EMD centre for the Region of Central Jutland (1.2 million
      people) opened on 1 December 2009. It was the first to employ health-care
      professionals and to use a new tool for criteria-based dispatch called Danish
      Index. The aim of the present paper is, for the first time in Denmark, to
      describe the level of urgency of patients transported by ambulance based on the
      Danish Index categories A-E and to determine if ambulance response time target
      values were reached. MATERIAL AND METHODS: The present paper is an observational
      cohort study based on consecutive, electronically collected data from the initial
      six months of operation (1 December 2009 to 31 May 2010) of the new EMD centre in
      Aarhus. RESULTS: A total of 73,484 patients were included. The distribution
      according to level of urgency was as follows:  A 28.7% (n = 21,104), B 13.5% (n =
      9,890), C 21.0% (n = 15,418), D 35.1% (n = 25,818), E 1.7% (n = 1,254). The
      median ambulance response time intervals for levels A and B were 6.5 and 11.9
      min., respectively. Comparison of level A response time intervals with the
      equivalent target values showed that the 75, 92 and 98 percentiles were 10.0/10
      min., 14.6/15 min., 18.6/20 min., respectively. CONCLUSION: In a cohort of 73,484
      patients, the highest level of urgency (A) was found in 28.7% of cases, while the
      largest group, 35.1% of patients, were level D cases - these patients had a need
      for transport, but not by ambulance. The level A target response time requested
      by 112 was achieved. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22142570
TI  - Multi-dose drug dispensing is a challenge across the primary-secondary care
      interface.
AB  - INTRODUCTION: Multi-dose drug dispensing (MDDD) signifies that the patient's
      medicine is packed in disposable bags corresponding to the dose that should be
      taken. The purpose of the present study was to investigate how a hospital MDDD
      instruction was followed. MATERIAL AND METHODS: All patients receiving MDDD on
      admission to the acute medical admission ward at Bispebjerg Hospital in the
      period from 1 January to 30 June 2010 were prospectively included in the study.
      An audit of the medication lists and hospital case records covering the period
      from admission to discharge was performed. A proportion of patients received a
      post-discharge home visit. An interview in both sectors was carried out to
      determine whether the instructions had been followed. RESULTS: Almost 9% of the
      patients were receiving MDDD on admission. Information on MDDD was recorded in
      the physician case record for 3.4% of the patients and in the nurse case record
      for 12.9% of the patients. Changes in MDDD during hospitalization were made for
      58.3% of the patients. General practitioners and/or the community pharmacy were
      notified of changes in MDDD at discharge for 13.6% of the patients. The post
      discharge visits and the interview revealed potential issues of concern regarding
      patient safety. CONCLUSION: MDDD is frequent. Identification and registration of
      MDDD is only performed sporadically. Changes in MDDD are frequent, but they are
      rarely accompanied by information to the general practitioner or the community
      pharmacy. FUNDING: The project was partly funded by the Ministry of Health and
      Prevention 2009. TRIAL REGISTRATION: The study was approved by the Danish Data
      Protection Agency.

PMID- 22142571
TI  - Cancer rates after kidney transplantation.
AB  - INTRODUCTION: Previous studies demonstrated a 3-5-fold increased cancer risk in
      kidney allograft recipients compared with the general population. Our aim was to
      estimate cancer frequencies among kidney allograft recipients who were
      transplanted in 1997-2000 and who were immunosuppressed according to a more
      modern steroid-free standard protocol based on basixilimab, ciclosporine and
      mycophenolate mofetil. MATERIAL AND METHODS: This was a retrospective cohort
      study of patients receiving their first kidney allograft in 1997-2000 at Odense
      University Hospital, Denmark (n = 90). Histologically verified cancers were
      identified from a detailed search of the individual patient's medical records.
      RESULTS: During an average follow-up time of 8.4 years, a total of 14 cancers
      were observed. The cancer incidence rate was 18.5 (95% confidence interval (CI):
      11.0-31.3) per 1,000 years, and the cancer prevalence was 13.4% (95% CI: 5.6
      21.2%) among survivors in 2007. The relative risk of prevalent cancer was 3.6
      (95% CI: 2.0-6.5) compared with the general population. Patients with cancer had
      a poorer survival than patients without cancer. CONCLUSION: The observed cancer
      incidence rate and prevalence were similar to figures derived from studies
      performed in the earlier eras of kidney transplantation. Reducing cancer rates
      after kidney transplantation remains an important challenge for nephrologists.
      FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22142572
TI  - Need for thyroidectomy in patients treated with radioactive iodide for benign
      thyroid disease.
AB  - INTRODUCTION: Nodular toxic and non-toxic goitres are seen in approximately 15%
      of Danish women, and the pros and cons of thyroidectomy versus radioiodine (RI)
      therapy are often discussed. The purpose of this study was to evaluate the type
      and number of patients treated on the indication of hyperthyroidism or benign
      goitre who did not achieve a sufficient effect of RI therapy and therefore needed
      thyroidectomy. MATERIAL AND METHODS: Between 1 January 2003 and 1 January 2008, a
      total of 873 patients were treated with RI on the indication of benign thyroid
      disease at Herlev Hospital (Denmark). Data concerning these patients were listed
      consecutively in a database. The data were subsequently cross-checked with the
      Danish Thyroid Surgery Quality Register (THYKIR) which contains data on all
      patients treated with thyroid surgery at Danish departments of ear, nose and
      throat and head and neck surgery since 1 January 2001. Patient data were also
      cross-checked with the National Patient Register data. The unique Danish social
      security numbers were used to compare data. RESULTS: Among the 873 patients
      treated with RI, 36 were listed in the THYKIR database. Eleven of these had
      primary thyroid surgery and subsequently underwent RI treatment due to goitre
      recurrence. Twenty-five patients first received RI therapy and subsequently
      thyroidectomy due to persisting symptoms (17 had non-toxic goitre and compression
      symptoms (among these eight had a large goitre with a thyroid volume of > 100 ml
      (range 100-389 ml)), five had nodular toxic goitre and three had diffuse toxic
      goitre and continuing hyperthyroidism despite RI treatment. Thyroid surgery
      revealed a small (2-3 mm) cancer in two patients, both from the group of patients
      with nodular toxic goitre. CONCLUSION: The effect of RI therapy sufficiently
      solved the problem (hyperthyroidism or goitre) and surgery was hence avoided in
      848 of 873 (97%) patients. However, within the group of patients with nontoxic
      goitre, a subgroup of patients with large goitres seems to be resistant to RI
      treatment and does not achieve sufficient effect under the current RI therapy
      regime. FUNDING: not relevant. TRIAL REGISTRATION: Danish Data Protection Agency
      (Datatilsynet) HEH.afd.O.750.86-7 and 2010-231-0068.

PMID- 22142573
TI  - Stagnation in body mass index in Denmark from 1997/1998 to 2004/2005, but with
      geographical diversity.
AB  - INTRODUCTION: We analyzed the trend in body mass index (BMI) as well as in the
      prevalence of overweight and obesity among Danish adults, mainly women, from
      1997/1998 to 2004/2005 and evaluated any regional differences. MATERIAL AND
      METHODS: Data were drawn from two cross-sectional population-based studies
      conducted in parallel in Aalborg and Copenhagen from 1997/1998 and 2004/2005.
      Height and weight were measured in a total of 7,487 participants in the two
      cohorts. RESULTS: In the total cohort, we found no significant difference in BMI
      from 1997/1998 to 2004/2005 (p = 0.828). There was an increase in BMI in Aalborg
      of 0.32 (p = 0.030), while in Copenhagen we observed a statistically significant
      decrease in BMI of 0.30 (p = 0.017). The difference in change over time in BMI
      between the two regions was significant (p = 0.002). Also the difference in the
      trend in prevalence of overweight and obesity was statistically significant
      between the two cities (p = 0.010). CONCLUSION: Our results indicate that the
      obesity epidemic is leveling off - at least among women - and that it may even be
      receding in Copenhagen. Nevertheless, the absolute average BMI values and the
      prevalence of overweight and obesity in both cities are high which underlines the
      need for further initiatives to prevent obesity-related health risks in the
      future. FUNDING: The DanThyr studies were supported by funding from the
      Tommerhandler Vilhelm Bang Foundation, the Copenhagen Corporation Research
      Foundation, the 1991 Pharmacy Foundation, the Danish Medical Foundation, the
      Health Insurance Foundation, the Agnes and Knut Mork Foundation, the Wedel
      Wedelsborg Foundation, the Ortho-Clinical Foundation and BRAHMS Diagnostica.
      TRIAL REGISTRATION: not relevant.

PMID- 22142574
TI  - Perceptions of herpes zoster and attitudes towards zoster vaccination among 50-65
      year-old Danes.
AB  - INTRODUCTION: Herpes zoster (HZ or shingles) and its complication post-herpetic
      neuralgia (PHN) are common in persons above 50 years of age. A vaccine that
      decreases the incidence and morbidity associated with HZ was licensed for use in
      2006 and will be marketed in Denmark as from 2013. This study aimed to explore
      the relations between illness perceptions of shingles and attitudes towards
      zoster vaccination. MATERIAL AND METHODS: Three qualitative focus group
      interviews were conducted with 22 patients, relatives and individuals with no
      personal experiences with HZ. Semi-structured interview guides were applied
      including questions identified in a literature study. The data were analysed
      using a medical anthropological approach. RESULTS: The study showed that HZ and
      PHN, in particular, have severe impacts on patients' quality of life (QoL) and
      often affect their relatives' daily lives as well. Nevertheless, people who have
      no experience with HZ underrate both its prevalence and its QoL impacts. Such
      misperceptions often result in delayed treatment and may lead to a low uptake of
      zoster vaccination. CONCLUSION: Individual attitudes towards zoster vaccination
      are closely related to subjective perceptions of HZ and views on vaccination in
      general. Vaccination recommendations to target groups are necessary, but
      individual choice is determined by knowledge about the disease, personal risk
      assessment and the recommendations of the general practitioner. FUNDING: The
      study was funded by a research grant from Sanofi Pasteur MSD. TRIAL REGISTRATION:
      not relevant.

PMID- 22142575
TI  - Improved survival of Danish cancer patients 2007-2009 compared with earlier
      periods.
AB  - INTRODUCTION: For the majority of cancers, improved long-term survival may be
      accessed from survival during the first year after diagnosis. A steady
      improvement in survival was seen both before and after the introduction of cancer
      control plans in 2000 and 2005. On the basis of data from 2007-2009, we studied
      the trend in 1-year survival after the introduction of the 2005 plan. MATERIAL
      AND METHODS: All cancers from 1995-2009 were studied in five 3-year cohorts of
      incident cases which were followed-up for death to the end of 2010. Age
      standardised 1-, 3- and 5-year relative survival was calculated and 1-year
      survival presented for 2004-2006 and 2007-2009 to allow comparison with our
      previous publication. RESULTS: The improvement over time in overall 1-year age
      standardised relative survival was maintained with a three percentage point
      increase to 72% for men and 75% for women. Exclusion of prostate and breast
      cancer from calculations lowered relative survival to 65% and 67%, respectively;
      but improvement was maintained. Cancer sites which previously enjoyed a high
      survival saw the least or no improvement as was the case for haematological
      cancers, except for non-Hodgkin lymphoma in men. The differences in survival
      between men and women are diminishing, especially for cancers of the digestive
      tract. CONCLUSION: The improvements over time in survival after introduction of
      the cancer plans were maintained for non-haematological cancers. The fast-track
      system for diagnosis and treatment introduced gradually by cancer sites until the
      end of 2008 along with some centralisation of elective surgery may have narrowed
      the gap in cancer survival between men and women for digestive tract cancers and
      may also have improved survival for other cancers, e.g. the sex-specific types
      and kidney and brain cancers. FUNDING: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 22142576
TI  - Short convalescence and minimal pain after out-patient Bascom's pit-pick
      operation.
AB  - INTRODUCTION: Treatment of pilonidal sinuses with Bascom's pit-pick operation can
      easily be performed under local analgesia. We describe pain during and after the
      operation, time to return to work, time to healing and success rate. MATERIAL AND
      METHODS: The study comprised a cohort of 75 primary pit-pick (PP) operations
      performed at our department between August 2007 and December 2009. The median age
      was 30 years (range 15-64 years) and 57 (76%) were male. A total of 55 patients
      were interviewed daily by phone for one week with a view to registering their
      ability to return to work and their scoring of maximum pain on a numerical rating
      scale with a pain score ranging from 0 (no pain) to 10. RESULTS: The mean maximum
      pain during the first post-operative day was 2.2 (95% confidence interval (CI)
      1.8-2.7) and at day four 1.0 (CI 0.7-1.3). Within 24 hours, 51% could return to
      work and the mean time was 3.2 (CI 1.8-4.5) days. Postoperative infection was
      related to the presence of secondary sinus (p = 0.03) and increasing number of
      midline sinus excisions (p = 0.02). Complete wound healing was achieved in 84% of
      the patients after a mean period of 3.5 (CI 3.1-3.9) weeks. Incomplete wound
      healing was significantly related to a small number of PPs (p < 0.05), increasing
      number of midline sinus excisions (p < 0.05) and no postoperative infection (p =
      0.01). At one-year follow-up 80% were considered successfully treated.
      CONCLUSION: The majority of patients with simple pilonidal sinuses can be treated
      successfully with Bascom's PP procedure as out-patients. This regimen causes only
      mild postoperative pain and patients can resume work after a few days. FUNDING:
      not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22142577
TI  - Communication with patients and colleagues.
AB  - BACKGROUND: Although patient-centred communication has provided a focus point in
      health care for many years, patient surveys continuously reveal serious
      communication problems as experienced by patients, due to poor communication.
      Likewise, poor inter-collegial communication can cause problems for both health
      care staff and patients. So, knowing that patient-centred communication and good
      inter-collegial communication is for the benefit of both health professionals and
      patients, the relevance of improving health care professionals' communication
      skills and investigating the effect on both professionals and patients is beyond
      doubt. AIM: The aim of this study was to investigate whether a training course in
      communication skills for health care professionals could improve: 1) Health care
      professionals' self-efficacy in communication with patients and colleagues 2)
      Health care professionals' evaluation of inter-collegial communication 3)
      Patients' experience of quality of care,   and to investigate health care
      professionals' experience of: a) participation in a communication skills training
      course b) the influence of the course on their ability to communicate with
      patients and colleagues. METHODS: The study was carried out in the Department of
      Orthopaedic Surgery, Kolding Hospital, a part of Lillebaelt Hospital, as an
      intervention study with baseline measurements and measurements after the
      intervention. The intervention was an in-house communication skills training
      course for all health care professionals at the department. The effect was
      measured partly on the health care professionals' self-efficacy and evaluation of
      inter-collegial communication, partly on patients' evaluation of quality of
      information, continuity and care. Data were collected by means of questionnaires
      and further explored by focus group interviews with health care professionals.
      RESULTS: A total of 181 health care professionals were included in the study. The
      questionnaire was completed by 177 (97.8%) before; 165/169 (97.6%) immediately
      after and 150/153 (98%) six months after the course. The health care
      professionals' self-efficacy was significantly increased, both for communication
      with patients and colleagues. The effect was still present six months after the
      training course. Also the health care professionals' evaluation of inter
      collegial communication showed significant improvements after the course; the
      effect was more pronounced for inter-professional than for intra-professional
      communication and more pronounced six months after than immediately after the
      course. A total of 32 health care professionals participated in the focus group
      interviews, which showed that, in general, nurses, nursing assistants, medical
      secretaries and managers principally experienced better control over the patient
      interview, increased confidence in communication, improved inter-collegial
      understanding and increased focus on patient-centred communication after the
      training course. The doctors had an overall negative experience of their
      participation in the training course, but nevertheless experienced positive
      changes in their communication after the course.   In the patient survey a total
      of 3660 patients answered the questionnaire from the 1st of May 2007 untill the
      31st of May 2010. The eligible response rates were 67.75% for the baseline
      measurement and 77.63% for the after measurement. There was a significant
      increase in patients responding "To a considerable extent" for 15/19 questions; a
      non-significant increase for 3/19 questions, and a statistically significant
      decrease for 1/19 question after the training course. CONCLUSION: The study has
      shown that a communication skills training course can improve health care
      professionals' self-efficacy in communication with both patients and colleagues
      and also improve inter-collegial communication. The focus group interviews showed
      that the most essential experiences of change were more confident communication
      with patients and colleagues and an increased patient-centredness. Furthermore,
      the study has shown a significant increase in patient satisfaction concerning
      information, continuity and care after the training course for health care
      professionals.

PMID- 22142578
TI  - Birth outcome in women with ulcerative colitis and Crohn's disease, and
      pharmacoepidemiological aspects of anti-inflammatory drug therapy.
AB  - The clinical epidemiological studies included in this thesis fall into three
      parts. The first part includes studies on birth outcome in women with ulcerative
      colitis. The second part includes pharmacoepidemiological studies on birth
      outcome after anti-inflammatory drug therapy in pregnancy, including patients
      with ulcerative colitis and Crohn's disease. The third part (and the latest
      publications) includes birth outcome in women with Crohn's disease; and the
      methods of cohort establishment in these studies are developed and improved due
      to the knowledge gathered from conducting the earlier studies.  The birth
      outcomes in women with ulcerative colitis are examined in a nationwide, Danish,
      cohort of women based on data from the Danish National Hospital Discharge
      Registry and the Danish Medical Birth Registry, and within a Hungarian case
      control data set. Our data suggest:   1) Significantly increased risk of preterm
      birth when women give birth 0-6 months after establishment of the diagnosis. It
      is considered whether the increased risk may be influenced by disease activity
      around the time of establishing the diagnosis.  2) No increased risk of giving
      birth to children with low birth weight, intrauterine growth retardation or
      congenital abnormalities (evaluated overall).  3) Significantly increased risk of
      some selected congenital abnormalities (limb deficiencies, obstructive urinary
      and multiple congenital abnormalities). No other studies have examined the risk
      of selected congenital abnormalities in children born by women with ulcerative
      colitis.  The pharmacoepidemiological studies on birth outcomes after use of anti
      inflammatory drug therapy in pregnancy, including women with ulcerative colitis
      and Crohn's disease, are based on data from the Hungarian case-control data set,
      a countywide Danish prescription Database, the Danish National Hospital Discharge
      Registry, the Danish Medical Birth Registry, and review of selected medical
      records. After exposure to sulfasalazine during pregnancy our data suggest.  No
      significantly increased overall relative risk of congenital abnormalities and no
      significantly increased risks of selected congenital abnormalities.  After
      exposure to 5-aminosalicylic acid during pregnancy our data suggest. No
      significantly increased relative risk of low birth weight, intrauterine growth
      retardation or congenital abnormalities (evaluated overall).   A significantly
      increased relative risk of preterm birth and stillbirth in ulcerative colitis
      women, compared to women with no prescription of reimbursed medicine in pregnancy
      - and also after comparing with women with chronic inflammatory bowel disease not
      taking 5-aminosalicylic acid during pregnancy. It is not clear whether these
      associations are causal or influenced by confounding by disease activity in
      particular. After maternal exposure to azathioprine/6-mercaptopurine during
      pregnancy our data suggest. An increased relative risk of preterm birth,
      congenital abnormalities, and perinatal mortality - also after using controls
      with similar underlying diseases.  It is difficult to rule out an influence of
      uncontrolled confounding. These were the first published data from a controlled
      observational study on exposed women with chronic inflammatory bowel disease. 
      After preconceptional paternal use of azathioprine/6-mercaptopurine our data
      suggest  An increased risk of congenital abnormalities, although not
      significantly increased.  The birth outcomes in women with Crohn's disease are
      examined in nationwide sub-cohorts classified according to type of anti
      inflammatory drug exposure during pregnancy, and based on data from the Danish
      National Hospital Discharge Registry, the nationwide Danish Prescription Database
      and the Danish Medical Birth Registry. Furthermore, birth outcomes are examined
      in Crohn's disease women with disease activity during pregnancy, based on data
      from review of hospital records, the Danish National Hospital Discharge Registry
      and the Danish Medical Birth Registry. Our data suggest: 1) The risk of adverse
      birth outcomes in women with Crohn's disease varies according to the type of anti
      inflammatory drug therapy in pregnancy. 2) Reassuring results according to low
      birth weight, intrauterine growth retardation, preterm birth and congenital
      abnormalities after use of sulfasalazine/5-aminosalicylic acid or steroids. 3)
      Worrisome findings of a significantly increased risk of preterm birth and an
      increased risk of congenital abnormalities (not significantly increased) after
      prescription of azathioprine/6-mercaptopurine during pregnancy. Some residual
      confounding by disease activity may have been left in the analyses of preterm
      birth.   In Crohn's disease women with disease activity during pregnancy our data
      suggest: 1) A significantly increased relative risk of preterm birth in women
      with the highest degree of disease activity during pregnancy. 2) Disease activity
      does not seem to increase the risk of low birth weight, intrauterine growth
      retardation or congenital abnormalities.  This study is the first epidemiological
      study of the risk of adverse birth outcomes in Crohn's disease women with disease
      activity during pregnancy, compared to women with no activity during pregnancy,
      and in which confounders have been taken into consideration.  Exceeding the
      studies included in my previous PhD thesis, this thesis provides new evidence on
      the following subjects: i) the risk of selected congenital abnormalities in
      children of women with ulcerative colitis, ii) pharmacoepidemiological studies on
      the risk of adverse birth outcome after maternal azathioprine/6-mercaptopurine
      exposure in pregnancy, and the risk of congenital abnormalities in children
      fathered by men treated with azathioprine/6-mercaptopurine before conception,
      iii) the risk of adverse birth outcome in women with Crohn's disease according to
      type of anti-inflammatory drug treatment in pregnancy (sulfasalazine/5
      aminosalicylic acid, steroids or azathioprine/6-mercaptopurine), and iv) the
      impact of disease activity in women with Crohn's disease on adverse birth
      outcome.  We learned from the studies in this thesis that the traditional way of
      reporting birth outcome in women with chronic inflammatory bowel disease, i.e.
      without having valid information on the type of underlying disease, concurrent
      therapeutic drug treatment and disease activity, is of limited value. The studies
      show that the risk of specific adverse birth outcome in women with ulcerative
      colitis and Crohn's disease depends on several factors including the time of
      birth in relation the debut of disease, the type of underlying disease
      (ulcerative colitis or Crohn's disease), the type of anti-inflammatory drug
      treatment during pregnancy, and the degree of disease activity during pregnancy.
      At the same time one also has to realize that the existing evidence is still
      limited, especially in the field of reproductive safety after therapeutic drug
      treatment during pregnancy and possible effects of preconceptional therapeutic
      drug exposure.

PMID- 22142579
TI  - Glucose-dependent Insulinotropic Polypeptide (GIP): From prohormone to actions in
      endocrine pancreas and adipose tissue.
AB  - The present thesis consists of one published article and one draft manuscript. 
      Interest in the incretin hormone glucose-dependent insulinotropic polypeptide
      (GIP) was reignited by the discovery that GIP receptor deficient mice were unable
      to gain weight in response to high fat feeding. However, the path from processing
      of the prohormone to regulation of secretion and establishment of its role in the
      complicated network of mediators involved in energy mobilization is not fully
      understood.   The biologically active GIP1-42 was found in vivo to be dependent
      on processing from the immature prohormone by proprotein convertase 1/3 (PC1/3)
      in the intestinal K-cell. Even so, ~50% of GIP immunoreactive cells  do not
      express PC1/3 raising the possibility that subsets of K-cells exist in which the
      precursor may be cleaved at alternative sites. Cell line studies did demonstrate
      that another convertase in endocrine cell types, PC2, mediated cleavage at
      alternative sites liberating larger and smaller GIP fragments. It was possible to
      detect fragments of similar size in gel filtration extracts of murine upper
      jejunum, but the identity, mechanism of processing and function of these
      immunoreactivities remains uncertain.  Once correctly processed GIP1-42 is
      secreted in response to food intake. The K-cell is believed to directly sense and
      respond to nutrients in the intestine, but as the molecular profiling of this
      cell type has just begun, the nutrient sensing machinery and possible feedback
      regulation are still poorly characterized.   When secreted to the blood stream,
      GIP acts as a mediator of energy mobilization in a complex network with other
      hormones. An acute and established function of GIP is to exert its incretin
      function thereby enhancing glucose stimulated insulin secretion necessary for
      prompt disposal of nutrients, yet GIP also stimulates glucagon secretion to
      increase blood glucose. In the diabetic state the insulinotropic effect of GIP is
      impaired and an early inexpedient glucagon stimulation in response to a meal
      further counteracts effects of insulin and worsens glycaemic control.   A
      demonstration that GIP receptor deficient mice were resistant to diet induced
      obesity let to the categorization of GIP as a fat promoting hormone and direct
      insulin-mimetic effects in adipose tissue has been proposed. We were able to
      demonstrate a redundancy for the GIP receptor in incorporation of lipids into
      adipocytes. We also observed that GIP receptor deficient mice could respond
      normally to high fat feeding with increased fat mass, but failed to increase lean
      mass. Mice with rescue of the GIP receptor in adipose tissue normalized the body
      composition in response to high fat diet, but the mice had a lower total body
      weight. In contrast, the GIP receptor expressed in the pancreatic beta-cell was
      able to promote lean mass gain on a low fat diet, but not on a high fat diet. 
      Overall, we have established principal requirements for GIP maturation.
      Furthermore, we have demonstrated that neither beta-cell nor adipocyte GIP
      receptor expression can replace the endogenous GIP receptor in regulation of body
      weight and body composition.

PMID- 22142580
TI  - Pain and convalescence following laparoscopic ventral hernia repair.
AB  - Severe pain is usual after laparoscopic ventral hernia repair (LVHR). Mesh
      fixation with titanium tacks may play a key role in the development of acute and
      chronic pain and alternative fixation methods should therefore be investigated.  
      This PhD thesis was based on three studies and aimed too:  1) assess the
      intensity and impact of postoperative pain by detailed patient-reported
      description of pain and convalescence after LVHR (Study I),  2) evaluate the
      feasibility of fibrin sealant (FS) for mesh fixation in an experimental pig model
      (Study II), and  3) investigate FS vs. tacks for mesh fixation in LVHR in a
      randomised, double-blinded, clinical controlled study with acute postoperative
      pain as the primary outcome (Study III).  In Study I - a prospective descriptive
      study - 35 patients were prospectively included and underwent LVHR. Scores of
      pain, quality of life, convalescence, fatigue, and general well-being were
      obtained from each patient. Follow-up was six months. Average pain from
      postoperative day (POD) 0-2 and POD 0-6 measured on a 0-100 mm visual analogue
      scale (VAS) was 61 and 48, respectively. Pain scores reached preoperative values
      at POD 30. The incidence of severe chronic pain was 7%. No parameter predicted
      postoperative pain significantly. Significant correlations were found between
      pain, and general well-being (rS= -0.8, p < 0.001), satisfaction (rS= -0.67, p <
      quality of life score (rS= -0.63, p < 0.001) six months postoperatively. Patients
      resumed normal daily activity at POD 14.   In Study II - a randomised
      experimental study in pigs - nine pigs were operated laparoscopically with
      insertion of two different meshes fixed with either FS or tacks. All pigs were
      euthanized on POD 30. The primary outcome parameter was strength of ingrowth
      between the mesh and the anterior abdominal wall. A mechanical peel test was
      performed for each tissue sample. The secondary outcome parameters were grade and
      strength of adhesions to the mesh, shrinkage and displacement/folding of the mesh
      and histological parameters. All nine pigs survived without complications until
      sacrifice. No meshes were displaced from their initial position at autopsy, but
      in two cases mesh folding was observed. No significant difference in strength of
      ingrowth was found between different fixation methods or mesh types. Furthermore,
      no significant difference was found in grade or strength of adhesions or any
      histological parameters.   In Study III - a randomised, controlled, double
      blinded, multicenter trial - 40 patients with umbilical hernia defects between
      1.5-5 cm, were randomly assigned to receive FS or titanium tacks for mesh
      fixation in LVHR. Patients, care givers and those assessing the outcomes were
      blinded to group assignment. The primary outcome was average pain from POD 0-2
      (VAS score). Secondary outcome parameters were fatigue, general well-being and
      time to resume normal daily activity. Follow-up was one month for all. Patients
      in the FS group reported significantly less pain at POD 0-2 (median VAS 38 (range
      6-98) vs. 60 (18-96), p = 0.01). Absolute VAS score difference between groups was
      20 mm (95% CI 4-35 mm) at activity, and 19 mm (95% CI 3-34 mm) at rest. Patients
      in the FS group reported significantly less discomfort from POD 0-2 and POD 0-10,
      compared with the tack group. No significant difference was found in fatigue
      score between groups. No significant difference in hospital stay, hernia
      diameter, or morphine consumption in the post anesthesia care unit was found
      between groups. Patients in the FS group resumed normal daily activity at POD 7
      (1-66) versus POD 18 (1-95) in the tack group (p = 0.03). No recurrences were
      observed. No adverse events or side effects were observed. No significant
      differences in predefined complications were found between groups.   In
      conclusion, pain is a significant clinical problem after LVHR with impact on
      general well-being, quality of life and patient satisfaction. This issue must
      have first priority in future ventral hernia repair research. It is now
      documented, that the simple application of fibrin glue instead of titanium tacks
      for mesh fixation in LVHR of defects < 5 cm significantly reduced acute pain,
      discomfort and the period of convalescence. Long-term follow-up will show the
      value of FS fixation in terms of chronic pain and recurrence. As FS potentially
      may solve many of the outcome problems associated with LVHR, future studies
      should include larger hernia defects including large incisional hernias, as the
      operative technique may be different.

PMID- 22142581
TI  - Guidelines for Percutaneous Dilatational Tracheostomy (PDT) from the Danish
      Society of Intensive Care Medicine (DSIT) and the Danish Society of
      Anesthesiology and Intensive Care Medicine (DASAIM).
AB  - Percutaneous dilatational tracheostomy is a common procedure in intensive care.
      This guideline from the Danish Society of Intensive Care Medicine (DSIT) and the
      Danish Society of Anesthesiology and Intensive Care Medicine (DASAIM) describes
      indications  and contraindications, timing, complications compared to surgical
      tracheostomy, anaesthesia and technique, decannulation strategy, as well as
      training and education.

PMID- 22142582
TI  - Pre-treatment diagnosis of endometrial cancer through a combination of CA125 and
      multiplication of neutrophil and monocyte.
AB  - AIM:  This study aimed to investigate the clinical value of pre-treatment
      leukocyte differential counts and the prediction of endometrial cancer using
      leukocyte markers. MATERIAL AND METHODS: Medical records of 238 women with
      pathologically confirmed endometrial cancer between March 2000 and June 2009 at
      two Korean hospitals were reviewed and compared to 596 healthy people visiting
      the Health Promotion Center in Gangnam Severance Hospital. For all study
      subjects, leukocyte differential counts and CA125 levels in serum obtained prior
      to operation were recorded. Multiplication of neutrophil and monocyte (MNM) was
      determined by multiplying neutrophil and monocyte counts then dividing by 10000.
      Differences between endometrial cancer patients and healthy controls were
      compared. The sensitivity and specificity for each marker as well as the combined
      use of CA125 and other leukocyte markers were assessed using receiver operating
      characteristic curves. RESULTS: Mean white blood cell (WBC) counts were 6676
      (6440-6913) cells/uL in endometrial cancer patients compared to 5663 (5542-5784)
      cells/uL in healthy controls (P<0.001). The area under curve (AUC) for CA125 was
      0.689 with a sensitivity of 49.13% and specificity of 83.1% using an optimal cut
      off value of 18.7U/mL. The AUC for MNM was 0.696 with a sensitivity of 62.9% and
      specificity of 69.1%. The combination of CA125 and MNM showed a higher AUC of
      0.760 than use of CA125 or MNM alone. CONCLUSION: The combination of MNM and
      CA125 is a simple and cost-effective method for predicting endometrial cancer.

PMID- 22142584
TI  - Vitamin D deficiency is associated with poor response to active hepatitis B
      immunisation in patients with chronic kidney disease.
AB  - Vitamin D deficiency is highly prevalent in patients suffering from chronic
      kidney disease. At present it is not known whether this condition is associated
      with poor response to hepatitis B vaccination in these patients. We performed a
      retrospective analysis of 200 patients with chronic kidney disease stages 3-5D,
      who had undergone hepatitis B vaccination with three 40 MUg recombinant hepatitis
      B vaccine doses in a single centre. Anti-HBs antibody titres and 25
      hydroxyvitamin D (25(OH)D) levels were measured by chemiluminescence
      immunoassays. Vitamin D deficiency with serum levels <10 ng/mL was found in 35.5%
      of patients. These patients had a lower seroconversion rate than did patients
      with levels >=10 ng/mL (45% vs 64%; P=0.011) and their median (25th, 75th
      percentile) anti-HBs antibody titres were lower (0 (0, 117)IU/L vs 48 (0,
      236.5)IU/L). Non-responders had lower 25(OH)D concentrations than did responders
      (12.9+/-6.5 ng/mL vs 15.1+/-7.4 ng/mL; P=0.034). Treatment with a vitamin D
      receptor activator had no influence on the immune response. In a multiple
      logistic regression analysis vitamin D deficiency (OR 0.480; P=0.023) and
      diabetes (OR 0.496; P=0.038) remained independent and significant negative
      predictors of seroconversion. In conclusion, in patients with chronic kidney
      disease vitamin D deficiency is associated with a poor antibody formation upon
      hepatitis B vaccination.

PMID- 22142583
TI  - An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes
      elicitation of antibody responses overlapping the CD4-binding site.
AB  - A major priority in HIV vaccine research is the development of an immunogen to
      elicit broadly neutralizing antibodies (NAbs). Monoclonal antibody (mAb) b12 is
      one of now several broadly neutralizing mAbs that bind epitopes overlapping the
      CD4-binding site (CD4bs) on HIV-1 gp120 and that serve as templates to engineer
      effective immunogens. We are exploring a strategy whereby extra glycans are
      incorporated onto gp120 to occlude the epitopes of non-neutralizing mAbs while
      maintaining exposure of the b12 site. Immunizing with these so-called
      hyperglycosylated gp120s is hypothesized to preferentially elicit b12-like NAbs.
      Here, the effects of two adjuvants, monophosphoryl lipid A (MPL) and Quil A, on
      eliciting b12-like responses when formulated with a new hyperglycosylated mutant,
      DeltaN2mCHO(Q105N), is presented. Sera from DeltaN2mCHO(Q105N)_MPL immunized
      animals bound the homologous antigen DeltaN2mCHO(Q105N) with greater preference
      than sera from DeltaN2mCHO(Q105N)_QuilA immunized animals, demonstrating the
      modulation of antibody fine specificity by these two adjuvants. We also found
      that sera from DeltaN2mCHO(Q105N)_QuilA immunized animals bound best to a
      resurfaced HIV gp120 core protein on which non-CD4bs epitopes are substituted
      with non-HIV residues, suggesting that these sera contain a relatively larger
      fraction of CD4bs-specific antibodies. Consistent with these data, inhibition
      assays revealed epitope overlap with the binding sites of the CD4bs-specific
      antibodies b12, b13 and VRC03. Unexpectedly, these sera did not exhibit
      significant neutralizing activity against a set of HIV-1 primary strains. Our
      results show that although formulating mutant DeltaN2mCHO(Q105N) with Quil A
      promotes the elicitation of CD4bs-directed antibodies relative to wild-type
      gp120, tweaking of the immunization regimen is needed to yield robust, CD4bs
      focused NAbs.

PMID- 22142585
TI  - Selection and characterization of vaccine strain for Enterovirus 71 vaccine
      development.
AB  - Enterovirus 71 (EV71) has recently emerged as an important neurotropic virus in
      Asia because effective medications and prophylactic vaccine against EV71
      infection are not available. Based on the success of inactivated poliovirus
      vaccine, the Vero cell-based chemically inactivated EV71 vaccine candidate could
      be developed. Identification of EV71 vaccine strain which can grow to high titer
      in Vero cell and induce cross-genotype virus neutralizing antibody responses
      represents the first step in vaccine development. In this report we describe the
      characterization and validation of a clinical isolate E59 belonging to B4 sub
      genotype based on VP1 genetic analysis. Before selected as the vaccine strain,
      the genetic stability of E59 in passage had been analyzed based on the nucleotide
      sequences obtained from the Master Virus Seed, Working Seed banks and the virus
      harvested from the production lots, and found to be identical to those found in
      the original isolate. These results indicate that E59 vaccine strain has strong
      genetic stability in passage. Using this vaccine strain the prototype EV71
      vaccine candidate was produced from 20L of Vero cell grown in serum-containing
      medium. The production processes were investigated, characterized and quantified
      to establish the potential vaccine manufacturing process including the time for
      virus harvest, the membrane for diafiltration and concentration, the gel
      filtration chromatography for the down-stream virus purification, and the methods
      for viral inactivation. Finally, the inactivated virion vaccine candidate
      containing sub-microgram of viral proteins formulated with alum adjuvant was
      found to induce strong virus neutralizing antibody responses in mice and rabbits.
      Therefore, these results provide valuable information for cell-based EV71 vaccine
      development.

PMID- 22142586
TI  - k(L)a as a predictor for successful probe-independent mammalian cell bioprocesses
      in orbitally shaken bioreactors.
AB  - The aim of this study was to gain a better understanding of orbitally shaken
      bioreactors (OSRs) operated without controllers for pH and dissolved oxygen (DO)
      concentration. We used cylindrical OSRs with working volumes ranging from 250mL
      to 200L to determine that the volumetric mass transfer coefficient of oxygen
      (k(L)a) is a good predictor of the performance of OSRs at different scales. We
      showed that k(L)a values of 7-10hour(-1) were required to avoid DO limitations
      and to prevent conditions of low pH during the cultivation of CHO cells. Overall,
      cell cultures in probe-independent OSRs of different nominal volumes ranging from
      250mL to 200L achieved similar cell densities, recombinant protein
      concentrations, and pH and DO profiles when having the same k(L)a. We conclude
      that k(L)a is a key parameter for probe-independent bioprocesses in OSRs and can
      be used as a scale-up factor for their operation.

PMID- 22142587
TI  - Secondary tics after osmotic demyelination syndrome involving both the striatum
      and the cerebral cortex.
AB  - Although some reports have associated parkinsonism, dystonia, and chorea with the
      extrapontine lesions of osmotic demyelination syndrome (ODS), to our knowledge
      delayed-onset tic disorder has not been reported. Thus, we report a rare
      secondary tic associated with ODS involving both the striatum and the cerebral
      cortex. We can hypothesize that aberrant neuronal plasticity after the initial
      insult in both basal ganglia and motor cortical areas could be implicated in the
      pathogenesis of delayed-onset tics.

PMID- 22142588
TI  - Spatial epidemiology of leptospirosis in Sri Lanka.

PMID- 22142589
TI  - Catalysis and regulation.

PMID- 22142590
TI  - Regulation of protein kinases by lipids.
AB  - Membranes are sites of intense signaling activity within the cell, serving as
      dynamic scaffolds for the recruitment of signaling molecules and their
      substrates. The specific and reversible localization of these signaling molecules
      to membranes is critical for the appropriate activation of downstream signaling
      pathways. Phospholipid-binding domains, including C1, C2, PH, and PX domains,
      play critical roles in the membrane targeting of protein kinases. Recent
      structural studies have identified a new membrane association domain, the Kinase
      Associated 1 (KA1) domain, which targets a number of yeast and mammalian protein
      kinases to membranes containing acidic phospholipids. Despite an abundance of
      localization studies on lipid-binding proteins and structural studies of the
      isolated lipid-binding domains, the question of how membrane binding is coupled
      to the activation of the kinase catalytic domain has been virtually untouched.
      Recently, structural studies on protein kinase C (PKC) have provided some of the
      first structural insights into the allosteric regulation of protein kinases by
      lipid second messengers.

PMID- 22142591
TI  - Overcoming instability and low solubility of new cytostatic compounds: a
      comparison of two approaches.
AB  - The pharmaceutical use of some 3-hydroxyquinolinone derivatives with high
      cytotoxic and cytostatic activities (under in vitro conditions) as well as
      potential immunosuppressive properties is seriously limited by their low
      solubility in water accompanied by instability in oxidative environment, like
      physiological fluids. In an attempt to improve the bioavailability and the
      stability of four of these derivatives, we propose here two different approaches:
      complexation with beta-cyclodextrin derivatives and incorporation of these
      substances inside antioxidant micelles. The comparison of the two different
      methods is the focus of this work, as well as the investigation of some
      physicochemical properties of the micellar aqueous dispersions. Antioxidant
      micellar dispersions appear to be suitable for increasing the apparent solubility
      and stability for all the compounds studied, most probably because of the
      antioxidant activity of the specific surfactant used, combined with the low
      amount of water present in the center of the micelles. On this regard, (1)H NMR
      and UV-vis spectroscopy result as efficient tools to verify that the drug
      molecules are indeed placed in the core of the micelles. Moreover, freeze-drying
      provides a very easy and powerful technique to obtain solid formulations starting
      from micellar dispersions. On the contrary, cyclodextrins could potentially be
      used as solubilizing agents, but the drawback connected to degradation in aqueous
      media could not be overcome with this type of solubilizer.

PMID- 22142592
TI  - Artemisinin and artemisinin plus curcumin liposomal formulations: enhanced
      antimalarial efficacy against Plasmodium berghei-infected mice.
AB  - The therapeutic efficacies of novel liposomal delivery systems based on
      artemisinin or artemisinin-based combination therapy with curcumin have been
      investigated and reported in this study. The developed liposomal formulations had
      proper characteristics as drug carriers for parental administration in terms of
      particle size, polydispersity, encapsulation efficacy and zeta-potential. Their
      physical and chemical stabilities were also evaluated. Furthermore, the in vivo
      antimalarial activity of artemisinin-based liposomal formulations was tested in
      Plasmodium berghei NK-65 infected mice, a suitable model for studying malaria
      because the infection presents structural, physiological and life cycle analogies
      with the human disease. Artemisinin, alone or in combination with curcumin, was
      encapsulated in conventional and PEGylated liposomes and its in vivo performance
      was assessed by comparison with the free drug. Mice were treated with artemisinin
      at the dosage of 50 mg/kg/days alone or plus curcumin as partner drug,
      administered at the dosage of 100 mg/kg/days. Artemisinin alone began to decrease
      parasitaemia levels only 7 days after the start of the treatment and it appeared
      to have a fluctuant trend in blood concentration which is reflected in the
      antimalarial effectiveness. By contrast, treatments with artemisinin-loaded
      conventional liposomes (A-CL), artemisinin-curcumin-loaded conventional liposomes
      (AC-CL), artemisinin-loaded PEGylated liposomes (A-PL), artemisinin-curcumin
      loaded PEGylated liposomes (AC-PL) appeared to have an immediate antimalarial
      effect. Both nanoencapsulated artemisinin and artemisinin plus curcumin
      formulations cured all malaria-infected mice within the same post-inoculation
      period of time. Additionally, all formulations showed less variability in
      artemisinin plasma concentrations which suggested that A-CL, AC-CL, A-PL and AC
      PL give a modified release of drug(s) and, as a consequence, a constant
      antimalarial effect during time. In particular, A-PL seems to give the most
      pronounced and statistically significant therapeutic effect in this murine model
      of malaria. The enhanced permanency in blood of A-PL suggests the use of these
      nanosystems as suitable passive targeted carriers for parasitic infections; this
      strong effect of formulation is added up to the mechanism of action of
      artemisinin which acts in the erythrocyte cycle stage of human host as a blood
      schizonticide.

PMID- 22142595
TI  - Dual field nonlinear dielectric spectroscopy in a glass forming EPON 828 epoxy
      resin.
AB  - Results of the dual field nonlinear dielectric spectroscopy (NDS) studies in
      supercooled glass forming epoxy resin EPON 828 are presented. For the NDS,
      changes of dielectric permittivity induced by DC (rectangular) or AC (sine-wave)
      pulses of a strong electric field were probed by a weak radio frequency electric
      field. A clear stretched exponential (x < 1) decay after switching off the DC
      pulse and a single exponential decay (x = 1) after switching off the AC pulse
      were found. The same results are presented for preliminary studies in
      superpressed low molecular glass former di-isobutyl phthalate. This observation
      may be considered as an argument for the heterogeneous picture of supercooled
      glass forming materials. The temperature dependences of the stationary responses
      related to DC and AC strong electric field excitations are also shown. The
      sensitivity of the applied set up made it possible to detect NDS outputs even for
      electric fields E(strong) < 10 kV cm(-1), qualitatively weaker than in similar
      'nonlinear, dielectric' experimental studies on glass forming materials carried
      out so far.

PMID- 22142594
TI  - Automated image analysis identifies signaling pathways regulating distinct
      signatures of cardiac myocyte hypertrophy.
AB  - Cardiac hypertrophy is controlled by a complex signal transduction and gene
      regulatory network, containing multiple layers of crosstalk and feedback. While
      numerous individual components of this network have been identified,
      understanding how these elements are coordinated to regulate heart growth remains
      a challenge. Past approaches to measure cardiac myocyte hypertrophy have been
      manual and often qualitative, hindering the ability to systematically
      characterize the network's higher-order control structure and identify
      therapeutic targets. Here, we develop and validate an automated image analysis
      approach for objectively quantifying multiple hypertrophic phenotypes from
      immunofluorescence images. This approach incorporates cardiac myocyte-specific
      optimizations and provides quantitative measures of myocyte size, elongation,
      circularity, sarcomeric organization, and cell-cell contact. As a proof-of
      concept, we examined the hypertrophic response to alpha-adrenergic, beta
      adrenergic, tumor necrosis factor (TNFalpha), insulin-like growth factor-1 (IGF
      1), and fetal bovine serum pathways. While all five hypertrophic pathways
      increased myocyte size, other hypertrophic metrics were differentially regulated,
      forming a distinct phenotype signature for each pathway. Sarcomeric organization
      was uniquely enhanced by alpha-adrenergic signaling. TNFalpha and alpha
      adrenergic pathways markedly decreased cell circularity due to increased myocyte
      protrusion. Surprisingly, adrenergic and IGF-1 pathways differentially regulated
      myocyte-myocyte contact, potentially forming a feed-forward loop that regulates
      hypertrophy. Automated image analysis unlocks a range of new quantitative
      phenotypic data, aiding dissection of the complex hypertrophic signaling network
      and enabling myocyte-based high-content drug screening.

PMID- 22142596
TI  - Marketing of dietetic products for infants and young children in Europe three
      decades after adoption of the International Code of Marketing of Breast Milk
      Substitutes.

PMID- 22142597
TI  - HPLC determination of arginases inhibitor N-(omega)-hydroxy-nor-L-arginine using
      core-shell particle column and LC-MS/MS identification of principal metabolite in
      rat plasma.
AB  - For the purpose of in vivo pharmacokinetic studies, an HPLC method was developed
      and validated for the quantification of N-(omega)-hydroxy-nor-L-arginine, L
      arginine and N-(omega)-ethyl-L-arginine (internal standard) in rat plasma. Sample
      processing involved a solid-phase extraction on the Waters MCX cartridges and on
      line pre-column derivatization of the analytes with o-phthaldialdehyde and 3
      mercaptopropionic acid. Separation of the derivatives was carried out on a core
      shell Kinetex C18 column in a gradient elution mode with a mobile phase
      consisting of methanol and water (pH=3.00 adjusted with formic acid).
      Fluorimetric detection with the excitation/emission wavelengths of 235/450 nm was
      used. The method was validated according to the FDA guidelines and applied to
      pilot pharmacokinetic experiments. An unknown metabolite was extracted from the
      plasma of Wistar rats after a single bolus of N-(omega)-hydroxy-nor-L-arginine
      (i.v. 10 mg kg(-1)). The metabolite was identified as nor-L-arginine using mass
      spectrometry. Validated method was successfully used for pilot pharmacokinetic
      experiment on rats.

PMID- 22142598
TI  - Occurrence and fate of organophosphorus flame retardants and plasticizers in
      coastal and marine surface waters.
AB  - This comprehensive study focused on the spatial and seasonal variations of
      organophosphorus flame retardants and plasticizers (OPs) in surface water from
      the estuary of the River Elbe and the German Bight (North Sea). 100 surface water
      samples were extracted by solid phase extraction (SPE) and analyzed by gas
      chromatography-mass spectrometry (GC-MS) with regard to 16 different OPs. The
      dominating substance was found to be tris(1-chloro-2-propyl) phosphate (TCPP)
      (Elbe: 40-250 ng L(-1), German Bight: 3-28 ng L(-1)). Furthermore, triethyl
      phosphate (TEP), tri-iso-butyl phosphate (TiBP), tris(2-butoxyethyl) phosphate
      (TBEP), and triphenylphosphine oxide (TPPO) were detected in concentrations up to
      180 ng L(-1). Seasonal trends were detected for the longitudinal profile of the
      Elbe estuary. Besides the dilution of river water with North Sea water toward the
      mouth, leading to decreasing concentrations at the four sampling cruises (March,
      May, August, and October, 2010), an additional depletion of non-halogenated OPs
      was observed in summer which is supposed to be due to biodegradation or
      photodegradation. In addition, a comparison of all important tributaries of the
      German Bight (Elbe, Ems, and Weser) as well as the indirect tributaries Meuse,
      Rhine, and Scheldt was done by multivariate statistical methods. It could be
      shown that the contribution of non-halogenated alkylated OPs in the Rhine was
      higher than in all other tributaries. The riverine input of OPs into the North
      Sea via the investigated tributaries was estimated to be about 50 tyr(-1).

PMID- 22142600
TI  - [Apps and tags for Ugeskrift for Laeger and the Danish Medical Journal].

PMID- 22142599
TI  - A novel two-step coprecipitation process using Fe(III) and Al(III) for the
      removal and immobilization of arsenate from acidic aqueous solution.
AB  - Lime neutralization and coprecipitation of arsenate with iron is widely practiced
      for the removal and immobilization of arsenic from mineral processing effluents.
      However, the stability of the generated iron-arsenate coprecipitate is still of
      concern. In this work, we developed a two-step coprecipitation process involving
      the use of iron and aluminum and tested the stability of the resultant
      coprecipitates. The two-step Fe-As-Fe or Fe-As-Al coprecipitation process
      involved an initial Fe/As = 2 coprecipitation at pH4 to remove arsenic from water
      down to 0.25 mg/L, followed by introduction of iron or aluminum (Fe/As = 2, Al/As
      = 1.5 or 2). The two-step coprecipitates showed higher stability than traditional
      Fe/As = 4 coprecipitate under both oxic and anoxic conditions. Leaching stability
      was enhanced when aluminum was applied in the second step. The use of aluminum in
      the second step also inhibited microbial mediated arsenate reduction and arsenic
      remobilization. The results suggest that the two-step coprecipitation process is
      superior to conventional coprecipitation methods with respect to the stability of
      the generated arsenic-bearing solid waste. The use of Al in the second step is
      better than Fe to enhance the stability. This work may have important
      implications to the development of new technologies for efficient arsenic removal
      from hydrometallurgical solutions and safe disposal in both oxic and anoxic
      environment.

PMID- 22142601
TI  - [Imaging modalities for finding almonds in rice deserts].
AB  - INTRODUCTION: In the traditional Danish Christmas dessert, ris a l'amande, one
      whole almond is hidden. The person who is lucky to find it in his portion is
      rewarded with a small gift, usually more sweets. We want to find out whether the
      hidden almond could be found by use of magnetic resonance imaging (MRI), computed
      tomography (CT) or conventional X-ray examinations. MATERIAL AND METHODS: We made
      three portions of ris a l'amande containing respectively three, one and zero
      whole almonds. All three portions were X-rayed and scanned by use of both MRI and
      CT, and three medical doctors from the neuroradiology department counted the
      almonds. All the three participants where blinded. RESULTS: We found that
      conventional X-ray was unsuitable for the purpose of finding whole almonds. In
      using either CT or MRI though, the hidden almonds were found. DISCUSSION: In a
      comparison between CT and MRI, the preferred modality is MRI, as diagnostic
      imaging confidence is higher with MRI as with CT. Ultrasound is another modality
      not tested, but potentially an excellent method for detecting almonds in ris a
      l'amande.

PMID- 22142602
TI  - [Gender differences among medical students in the approach to simulation].
AB  - INTRODUCTION: Simulation-based training is gaining ground as a replacement for
      the "apprenticeship" model of training. For this reason, it is useful to know if
      men and women have the same prerequisites and assumptions prior to training. The
      purpose of the study was to investigate whether male and female medical students
      performed differently whilst training in a bronchoscope simulator. MATERIALS AND
      METHODS: At a medical conference in Copenhagen, 62 medical students took part in
      a simulator experiment (number of male students: 33, number of female students:
      29). Data collection was obtained from the bronchoscope simulator. The
      participant's task was to identify and visualise as many orifices as possible
      during five minutes, without impinging on the mucous membranes. RESULTS: The male
      participants visualised a significantly higher amount of segments (p = 0,045)
      than the female participants, however there were also significantly more
      incidences of impingement on nearby mucous membranes in the male group of
      students (p = 0,045). At Copenhagen Medical School, there are almost twice as
      many female students as male students. Thus, gender distribution among the
      participants in this study does not reflect the gender distribution at a Danish
      medical school. This implies that men's interest in simulation is higher than the
      one of women's, and the results suggest a gender difference in the approach to
      simulation based training. CONCLUSION: Gender differences should be taken into
      consideration, when planning and organising medical education and assessment in
      simulation training.

PMID- 22142603
TI  - [Laypersons can seek help from their Facebook friends regarding medical
      diagnosis].
AB  - INTRODUCTION: In contrast to Internet search engines, social media on the
      Internet such as Facebook, Twitter, etc. reach a large number of people, who are
      ready to help answering questions. This type of information aggregation has been
      dubbed "crowdsourcing" i.e. outsourcing a task to a large group of people or
      community (a crowd) through an open call. Our aim was to explore whether
      laypersons via Facebook friends could crowd source their way to a medical
      diagnosis based on a brief medical history, posted as a status update on
      Facebook. MATERIAL AND METHODS: The participants posted a brief case story on
      their Facebook profile and asked their "Facebook friends" to come up with
      possible diagnoses. RESULTS: The correct diagnosis was suggested in five of the
      six case stories, and the correct diagnosis was made after a median of ten
      minutes. The quality of the responses varied from relevant differential diagnoses
      to very silly diagnostic suggestions. CONCLUSION: Based on this study, we believe
      that laypersons can use his or her "Facebook friends" to identify the need to see
      a doctor for their symptoms rather than relying on them to give them a specific
      diagnosis for their symptoms.

PMID- 22142604
TI  - [A peaceful Christmas Eve at the hospital].
AB  - INTRODUCTION: The aim of this study was to investigate admittance rates and
      doctors workload during Christmas. In addition, we examined if admittance data
      supports the common notions that overeating during Christmas results in increased
      rate of admittances for abdominal problems and that there is an increase in
      admittance of the elderly at the end of Christmas (i.e. "granny dumping").
      MATERIAL AND METHODS: A retrospective study analyzing data from the database of
      the hospital units of Sydvestjysk Sygehus was performed. Data covered admittance
      in the months spanning from November through January in 1994-2010. Data from
      Christmas was compared with data from adjacent months. RESULTS: During Christmas
      more patients with abdominal complaints were admitted to the hospital (p <
      0.001). However, there were no differences in mortality for patients with
      abdominal complaints or heart disease. There was a significant increase of
      patients admitted primarily because of lack of care at home during Christmas (p <
      0.001). The number of admittance reached an absolute minimum on Christmas Eve. No
      increased admittance among the elderly at the end of Christmas was observed in
      our data. CONCLUSION: We conclude that overeating during the festivities of
      Christmas probably results in increased admittance rates in Danish hospitals.
      Christmas Eve is the day on which doctors can expect the lowest workload.
      Although the rate of admission due to lack of care at home was high, we could
      find no evidence of "granny dumping".

PMID- 22142605
TI  - [Medical novels as a supplement to medical literature in the (postgraduate) study
      of medicine].
AB  - INTRODUCTION: Medically relevant fiction and biographies are thought to possibly
      improve the reader's emotional competences, thus contributing to the
      (postgraduate) study of medicine. This paper evaluates whether medical novels
      might be relevant in the (postgraduate) study of medicine. MATERIALS AND METHODS:
      The contents of four medical novels were evaluated qualitatively as regard to the
      professional and cultural contents and relevance. RESULTS: The medical novels
      were composed uniformly and considered to be both professional and cultural
      subjects. The professional subjects were mostly described correctly, and milieu
      and cultural subjects were realistic. DISCUSSION: The contents of the medical
      novels were relevant, but briefly described. Students of medicine and junior
      doctors may identify with the environment and the cultural subjects. It is not
      ruled out that medical novels can be used to acquire cultural competences, but -
      as regards professional knowledge - the study of professional literature will be
      more time-effective.

PMID- 22142606
TI  - [Pine mouth syndrome: a global problem].
AB  - Pinemouth syndrome is characterised by the development of metallogeusia two days
      after the ingestion of Chinese pine nuts. The symptoms disappear 7-14 days later.
      The distribution of Chinese pine nuts not suitable for human consumption, is
      caused by an increasing demand due to price differences. The reason for the taste
      disturbances is unknown, some suggest turpentine-based products in its
      composition, and others have studied the fatty acid content of pine nuts and the
      properties of pinolenic acid. So far the presence of pesticides or mycotoxins is
      been ruled out, but the puzzle remains unsolved.

PMID- 22142607
TI  - [An unusual case of a screwdriver found in rectum].
AB  - The presence of foreign bodies in the rectum is not an entirely rare cause for
      patients to seek hospital if the foreign body is stuck. Complications are rare (<
      1%) but potentially severe, since intraabdominal perforations can occur. We
      report a case of a 58 year-old male presenting with an abscess in the left
      gluteal region caused by a perforating screwdriver in the rectosigmoideum. The
      screwdriver was removed during a laparotomy and he got a temporary stoma but made
      complete recovery, and a stoma reversal was planned. The risk of insufficient
      patient counselling due to taboos is discussed.

PMID- 22142608
TI  - [Treatment with disulfiram can be dangerous].
AB  - A 66 year-old woman developed severe hypotension and bronchospasm as a result of
      disulfiram-ethanol reaction (DER). She presented with sudden onset of severe life
      threatening symptoms. The clinical signs of DER were treated successfully and
      symptomatically with intravenous fluids, catecholamines, inhalations and
      benzodiazepines in the intensive care unit. Fomepizole, an alcohol dehydrogenase
      inhibitor, was advocated as a specific treatment for DER. This case highlights
      the potential danger of DER.

PMID- 22142609
TI  - [Military assistance in transportation of patients for an emergency PCI
      intervention].
AB  - Patients with ST-elevation myocardial infarction (STEMI) are treated with primary
      percutaneous coronary intervention (pPCI) or fibrinolysis. pPCI is superior to
      fibrinolysis when initiated timely. However, geography and weather sometimes
      become obstacles for transporting the patient to a PCI centre. In this case story
      teamwork between hospital instances and the military enabled transport to a PCI
      centre for a PCI intervention even though the weather conditions were
      unfavourable.

PMID- 22142610
TI  - [A small bird gives severe consequences].
AB  - In this case we report how a 31 year-old woman developed hypersensitivity
      pneumonitis due to her budgerigar. The suspicion that her pet was the reason for
      her symptoms was confirmed by the finding of specific IgG antibodies against
      budgerigar proteins. Clinical studies demonstrated a restrictive lung disorder,
      increased lymphocytes in bronchoalveolar lavage and ground glass changes in high
      resolution computed tomography. The patient's symptoms receded over the course of
      a few days after removal of the animal, and subsequent IgG levels fell.

PMID- 22142611
TI  - [Perforation of maxillary sinus following fall against nutcracker].
AB  - We present a case of open fracture of maxillary sinus following fall against a
      nutcracker. The only pathological findings were a small wound and subcutaneous
      emphysema in the front of and behind the right maxillary sinus. There was no
      flattening of the anterior wall of the maxillary sinus, consequently no surgical
      intervention was performed. The patient was treated with prophylactic antibiotics
      and sutures. No sequelae were observed.

PMID- 22142612
TI  - [Picture of the month: F18-FDG-PET/CT].

PMID- 22142614
TI  - Synthesis, antiproliferative activity and genotoxicity of novel anthracene
      containing aminophosphonates and a new anthracene-derived Schiff base.
AB  - A new Schiff base, 9-anthrylidene-furfurylamine and three novel anthracene
      containing alpha-aminophosphonates, [N-methyl(dimethoxyphosphonyl)-1-(9-anthryl)]
      p-toluidine, [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]-p-toluidine and [N
      methyl(diethoxyphosphonyl)-1-(9-anthryl)]furfurylamine were synthesized. The
      compounds have been characterized by elemental analysis, TLC, IR, NMR and
      fluorescent spectra. The aminophosphonates and their synthetic precursors were
      tested for in vitro antitumor activity on a panel of seven human epithelial
      cancer cell lines. Safety testing was performed both in vitro (3T3 NRU test) and
      in vivo on ICR mice for genotoxicity and antiproliferative activity. 9
      Anthrylidene-furfurylamine and [N-methyl(diethoxyphosphonyl)-1-(9
      anthryl)]furfurylamine were most potent cytotoxic agents towards colon carcinoma
      cell line HT-29. The latter compound exhibited also antiproliferative activity to
      HBL-100, MDA-MB-231 and 647-V cells. The aminophosphonate [N
      methyl(dimethoxyphosphonyl)-1-(9-anthryl)]-p-toluidine and its synthetic
      precursor 9-anthrylidene-p-toluidine were found to be cytotoxic to HBL-100 and HT
      29 tumor cell lines, respectively. Moderate genotoxic and antiproliferative
      activity in vivo and low toxicity to Balb/c 3T3 (clone 31) mouse embryo cells
      were observed for all tested compounds. The subcellular distribution of two
      tested compounds in a tumor cell culture system was also studied.

PMID- 22142615
TI  - Mefloquine-oxazolidine derivatives, derived from mefloquine and
      arenecarbaldehydes: In vitro activity including against the multidrug-resistant
      tuberculosis strain T113.
AB  - Ten new mefloquine-oxazolidine derivatives, 4-[(1S,8aR)-3
      (aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline
      (1: aryl=substituted phenyl) and 4-[(1S,8aR)-3
      (heteroaryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8
      bis(trifluoromethyl)quinoline [2: heteroaryl=5-nitrothien-2-yl (2a); 5-nitrofuran
      2-yl (2b) and 4H-imidazol-2-yl) (2c)], have been synthesized and evaluated
      against Mycobacterium tuberculosis. Compounds 1f (aryl=3-ethoxyphenyl), 1g
      (Ar=3,4,5-(MeO)(3)-C(6)H(2)) and 2c were slightly more active than mefloquine
      (MIC=33MUM) with MICs=24.5, 22.5 and 27.4, respectively, whereas compounds 1e
      (aryl=3,4-(MeO)(2)-C(6)H(3)) and 2a (MICs=11.9 and 12.1MUM, respectively) were
      ca. 2.7 times more active than mefloquine, with a better tuberculostatic activity
      than the first line tuberculostatic agent ethambutol (MIC=15.9). The compounds
      were also assayed against the MDR strain T113 and the same MICs were observed.
      Thus the new derivatives have advantages over such anti-TB drugs as isoniazid,
      rifampicin, ethambutol and ofloxacin, for which this strain is resistant. The
      most active compounds were not cytotoxic to Murine Macrophages Cells in a
      concentration near their MIC values.

PMID- 22142613
TI  - Amide-modified prenylcysteine based Icmt inhibitors: Structure-activity
      relationships, kinetic analysis and cellular characterization.
AB  - Human protein isoprenylcysteine carboxyl methyltransferase (hIcmt) is the enzyme
      responsible for the alpha-carboxyl methylation of the C-terminal isoprenylated
      cysteine of CaaX proteins, including Ras proteins. This specific
      posttranslational methylation event has been shown to be important for cellular
      transformation by oncogenic Ras isoforms. This finding led to interest in hIcmt
      inhibitors as potential anti-cancer agents. Previous analog studies based on N
      acetyl-S-farnesylcysteine identified two prenylcysteine-based low micromolar
      inhibitors (1a and 1b) of hIcmt, each bearing a phenoxyphenyl amide modification.
      In this study, a focused library of analogs of 1a and 1b was synthesized and
      screened versus hIcmt, delineating structural features important for inhibition.
      Kinetic characterization of the most potent analogs 1a and 1b established that
      both inhibitors exhibited mixed-mode inhibition and that the competitive
      component predominated. Using the Cheng-Prusoff method, the K(i) values were
      determined from the IC(50) values. Analog 1a has a K(IC) of 1.4+/-0.2MUM and a
      K(IU) of 4.8+/-0.5MUM while 1b has a K(IC) of 0.5+/-0.07MUM and a K(IU) of 1.9+/
      0.2MUM. Cellular evaluation of 1b revealed that it alters the subcellular
      localization of GFP-KRas, and also inhibits both Ras activation and Erk
      phosphorylation in Jurkat cells.

PMID- 22142618
TI  - Determination of atomoxetine and its metabolites in conventional and non
      conventional biological matrices by liquid chromatography-tandem mass
      spectrometry.
AB  - A procedure based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) is
      described for determination of atomoxetine (ATX) and its metabolites 4
      hydroxyatomoxetine (4-OH-ATX) and N-des-methylatomoxetine (N-des-ATX) in plasma,
      urine, oral fluid and sweat using duloxetine as internal standard. Analytes were
      extracted from 0.5 mL biological fluids and sweat patch with 2 mL aliquots of
      tert-butyl methyl ether. The organic layer was evaporated and redissolved in
      mobile phase. Chromatographic separation was carried out on reverse-phase column
      and an isocratic mobile phase formed by 40% water and 60% 5mM ammonium acetate,
      47.2 mM formic acid, 4 mM trifluoroacetic acid in acetonitrile-water (85:15, v/v)
      at a flow rate of 0.5 mL/min. Separated analytes were identified and quantified
      by positive electrospray ionization tandem mass spectrometry and in multiple
      reaction monitoring acquisition mode. Limits of quantifications for the three
      analytes were 0.5 ng/mL plasma and oral fluid, 10 ng/mL urine and 1 ng/patch
      using 0.5 mL biological fluids or one sweat-patch per assay. Calibration curves
      were linear over the calibration ranges with r2>0.99. At three concentrations
      spanning the linear dynamic range of the assay, mean recoveries in different
      biological matrices were always higher than 65%. This method was applied to
      therapeutic monitoring of ATX and its metabolites 4-OH-ATX and N-des-ATX in
      conventional and non-conventional biological matrices from individuals in drug
      treatment.

PMID- 22142616
TI  - Mitochondrial DNA nucleoid structure.
AB  - Eukaryotic cells are characterized by their content of intracellular membrane
      bound organelles, including mitochondria as well as nuclei. These two DNA
      containing compartments employ two distinct strategies for storage and readout of
      genetic information. The diploid nuclei of human cells contain about 6 billion
      base pairs encoding about 25,000 protein-encoding genes, averaging 120 kB/gene,
      packaged in chromatin arranged as a regular nucleosomal array. In contrast, human
      cells contain hundreds to thousands of copies of a ca.16 kB mtDNA genome tightly
      packed with 13 protein-coding genes along with rRNA and tRNA genes required for
      their expression. The mtDNAs are dispersed throughout the mitochondrial network
      as histone-free nucleoids containing single copies or small clusters of genomes.
      This review will summarize recent advances in understanding the microscopic
      structure and molecular composition of mtDNA nucleoids in higher eukaryotes. This
      article is part of a Special Issue entitled: Mitochondrial Gene Expression.

PMID- 22142619
TI  - Rapid characterization of caged xanthones in the resin of Garcinia hanburyi using
      multiple mass spectrometric scanning modes: the importance of biosynthetic
      knowledge based prediction.
AB  - Although the anticancer activities of the resin of Garcinia hanburyi have been
      well demonstrated, the chemical composition of this medicinal plant is still not
      fully understood. In this study, a highly effective qualitative method was
      developed for rapidly profiling the target and non-target caged xanthones in the
      resin of G. hanburyi. This method mainly involves three steps as follows: (1)
      prediction of the possible unknown caged xanthones in the resin of G. hanburyi
      according to the structure characters of the known ones and some well established
      biosynthetic knowledge; (2) structure classification according to the diagnostic
      fragment ions (DFIs) of the known caged Garcinia xanthones; (3) detection and
      characterization of the target and non-target caged xanthones in the resin of G.
      hanburyi using multiple mass spectrometric (MS) scanning modes. By use of such
      procedures, mass spectrometric data can be used for confirming the rationally
      predicted chemical structure rather than sophisticated and time-consumed de novo
      structure elucidation of a completely unknown component. Finally, a total of 34
      caged xanthones including 18 likely new ones from the resin of G. hanburyi were
      rapidly detected and characterized within one working day.

PMID- 22142620
TI  - Extreme all-cause mortality in JUPITER requires reexamination of vital records.
AB  - OBJECTIVE: To compare all-cause mortality in JUPITER with other statin trials at
      21 months of follow-up. BACKGROUND: Outcome advantages including all-cause
      mortality reduction yielded from the JUPITER trial support aggressive use of
      rosuvastatin and, perhaps by extension, other statins for primary prevention.
      Despite enrolling apparently healthy subjects and early trial termination at 21
      months of mean follow-up, JUPITER revealed very high all-cause mortality in both
      the placebo (2.8%) and rosuvastatin (2.2%) arms. METHODS: Comparison of all-cause
      mortality prorated for 21 months in 10 primary prevention studies and 1 acute
      coronary syndromes statin trial. FINDINGS: The all-cause mortality in JUPITER was
      more than twice that of the average of primary prevention studies, matching well
      only with specific trials designed in diabetics (ASPEN or CARDS), early
      hypertension studies (ALLHAT-LLT) or a trial in patients with acute coronary
      syndromes (PROVE IT). Since the 'play of chance' is unlikely to explain these
      discrepancies due to excellent baseline match, excess death rates and all-cause
      mortality rates in both JUPITER arms must be questioned. It may be important that
      the study sponsor self-monitored sites. CONCLUSIONS: Excess all-cause mortality
      rates in the apparently relatively healthy JUPITER population are alarming and
      require independent verification. If, indeed, the surprising outcomes in JUPITER
      are successfully challenged, and considering established harm of statins with
      regard to rhabdomyolysis as well as, potentially, diabetes, millions of patients
      may find better and safer options for primary prevention of vascular events.

PMID- 22142621
TI  - A comprehensive model of hyaluronan turnover in the mouse.
AB  - The metabolism of hyaluronan (HA), especially its catabolism, is still far from
      being elucidated. Although several studies suggest that HA is degraded locally in
      tissues and through the lymphatic or circulatory systems, much needs to be
      learned about the enzymes, receptors and cell types that support this dynamic
      process. In the current work, the clearance of exogenously administered HA was
      examined in a C57BL/6 mouse model. Hyaluronidase-sensitive fluorescein-labeled
      1.2MDa hyaluronan (flHA) was administered either intravenously (i.v.) or
      subcutaneously (s.c.) into wild type C57BL/6 mice. Plasma was sampled for
      pharmacokinetic analysis and tissues were harvested for histological examination
      of the cell types responsible for uptake using immunofluorescent localization and
      for size exclusion chromatography analysis. We observed that flHA could be
      degraded locally in the skin or be taken up by sinusoidal cells in lymph nodes,
      liver and spleen. I.v. administration of flHA revealed non-linear Michaelis
      Menten pharmacokinetics compatible with a saturable, receptor-mediated clearance
      system (K(m)=11.6MUg/ml+/-46.0%, V(max)=1.69MUg/ml/min+/-59.7%). Through a
      combination of immunofluorescence microscopy, pharmacokinetic, and
      chromatographic analyses of labeled substrate in vivo, our results shed
      additional light on the mechanisms by which HA is catabolized in mammals, and
      serve as a basis for future studies.

PMID- 22142623
TI  - Predicting template-based catalysis rates in a simple catalytic reaction model.
AB  - We show that in a particular model of catalytic reaction systems, known as the
      binary polymer model, there is a mathematical concordance between two versions of
      the model: (1) random catalysis and (2) template-based catalysis. In particular,
      we derive an analytical calculation that allows us to accurately predict the
      (observed) required level of catalysis in one version of the model from that in
      the other version, for a given probability of having self-sustaining
      autocatalytic sets exist in instances of both model versions. This provides a
      tractable connection between two models that have been investigated in
      theoretical origin-of-life studies.

PMID- 22142622
TI  - A computational model of auxin and pH dynamics in a single plant cell.
AB  - Directed cell-to-cell movement of the plant growth hormone auxin is often
      referred to as polar auxin transport, and has gained much interest since its
      discovery at the beginning of the 20th century, both by biologists and
      theoreticians. Computational modelling of auxin transport at tissue and whole
      plant scales has given valuable insights into the feedback dynamics between auxin
      and its transport, which often leads to cell polarisation. However, one cellular
      feedback mechanism that has been overlooked so far in previous models is the
      interplay between auxin and pH during auxin transport, even though this is well
      known from biology. We propose a kinetic model of such a feedback mechanism,
      linking knowledge about auxin-induced acidification of cell wall compartments to
      the chemiosmotic hypothesis of auxin transport. Our results suggest that proton
      fluxes may play a significant role in auxin transport. Since active auxin
      transport relies on the proton motive force over the cellular membrane,
      allocation of auxin is linked to its effects on compartmental pH. Our auxin/pH
      feedback model predicts enhanced accumulation of auxin in cells and increases in
      both auxin influx and efflux when this feedback is in effect. These results were
      robust in all simulations and consistent with biological evidence, thus providing
      a framework for generating and testing hypotheses of auxin-related polarisation
      events at a cellular level.

PMID- 22142624
TI  - Distribution of branch lengths and phylogenetic diversity under homogeneous
      speciation models.
AB  - The constant rate birth-death process is a popular null model for speciation and
      extinction. If one removes extinct and non-sampled lineages, this process induces
      'reconstructed trees' which describe the relationship between extant lineages. We
      derive the probability density of the length of a randomly chosen pendant edge in
      a reconstructed tree. For the special case of a pure-birth process with complete
      sampling, we also provide the probability density of the length of an interior
      edge, of the length of an edge descending from the root, and of the diversity
      (which is the sum of all edge lengths). We show that the results depend on
      whether the reconstructed trees are conditioned on the number of leaves, the age,
      or both.

PMID- 22142625
TI  - Long time evolution of atherosclerotic plaques.
AB  - The evolution of atherosclerosis in general, and the influence of wall shear
      stress on the growth of atherosclerotic plaques in particular, is an intricate
      phenomenon which is still only partly understood. We therefore propose a
      qualitative mathematical model which consists of a number of ordinary
      differential equations for the concentrations of the most relevant constituents
      of the atherosclerotic plaque. These equations were studied both for the case
      that the wall shear stress is a parameter (model A), and for the case in which
      the plaque evolution is coupled to the blood flow (model B) which results in a
      time dependent wall shear stress. We find that both models exhibit a class of
      marginally stable equilibria, all reflecting states in which the plaque only
      grows for a short period of time after a perturbation. The uncoupled model A,
      however, shows bi-stability between this class of equilibria and another
      equilibrium state in which the plaque experiences unlimited growth in time, if
      the LDL cholesterol intake exceeds a threshold value. In model B the bi-stability
      vanishes, but we find that there is still a critical value of the LDL cholesterol
      intake beyond which the lumen radius drastically decreases. We show that this
      decrease is quite sensitive to the value of the wall shear stress.

PMID- 22142626
TI  - On the accuracy of the melting curves drawn from modelling a solid as an elastic
      medium.
AB  - An ongoing problem in the study of a classical many-body system is the
      characterization of its equilibrium behaviour by theory or numerical simulation.
      For purely repulsive particles, locating the melting line in the pressure
      temperature plane can be especially hard if the interparticle potential has a
      softened core or contains some adjustable parameters. A method is hereby
      presented that yields reliable melting-curve topologies with negligible
      computational effort. It is obtained by combining the Lindemann melting criterion
      with a description of the solid phase as an elastic continuum. A number of
      examples are given in order to illustrate the scope of the method and possible
      shortcomings. For a two-body repulsion of Gaussian shape, the outcome of the
      present approach compares favourably with the more accurate but also more
      computationally demanding self-consistent harmonic approximation.

PMID- 22142627
TI  - Upregulation of hepatic 11beta-hydroxysteroid dehydrogenase-1 expression in
      calcium-deficient rats.
AB  - BACKGROUND: Many epidemiologic studies have reported a link between calcium (Ca)
      deficiency and metabolic syndrome. In this study, we examine Ca deficiency in
      rats and whether changes in glucocorticoid metabolism are induced. METHODS:
      Twelve-week-old female Wistar rats were weaned onto a very-low-Ca diet (low-Ca
      group) or a control diet (control group) for 2 weeks. Quantitative real-time PCR
      was used to assess mRNA for 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1),
      11beta-HSD2, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated
      receptor-alpha, and glucocorticoid receptor in the liver. Concentrations of
      adiponectin, leptin, corticosterone, intact parathyroid hormone, asymmetrical
      dimethylarginine and insulin in fasting serum were determined using a rat
      specific enzyme-linked immunosorbent assay. Glucose concentrations were measured
      using a glucose oxidase system. Serum ionized Ca levels were measured with an
      automatic ion-selective electrode analyzer. Serum nitrite/nitrate levels were
      measured using a colorimetric assay kit. RESULTS: After 2 weeks, no differences
      in serum glucose, corticosterone or insulin levels were observed. The low-Ca
      group rats showed higher homeostasis model assessment insulin resistance, lower
      adiponectin and higher intact parathyroid hormone levels. Serum nitrite/nitrate
      and asymmetrical dimethylarginine were significantly higher in the low-Ca group
      than in the control group. The expression of hepatic 11beta-HSD1 mRNA was
      upregulated, while hepatic phosphoenolpyruvate carboxykinase expression was
      downregulated in the low-Ca group. Glucocorticoid receptor, peroxisome
      proliferator-activated receptor-alpha and 11beta-HSD2 expression levels showed a
      similar tendency. CONCLUSION: A low-Ca diet alters glucocorticoid metabolism,
      which leads to hepatic upregulation of 11beta-HSD1, and is possibly a key
      mechanism inducing the metabolic complications of Ca deficiency.

PMID- 22142628
TI  - Australian farmed Yellowtail Kingfish (Seriola lalandi) and Mulloway (Argyrosomus
      hololepidotus): residues of metallic, agricultural and veterinary chemicals,
      dioxins and polychlorinated biphenyls.
AB  - Composite samples of Australian farmed Yellowtail Kingfish (Seriola lalandi)
      (YTKF) (n=27), Mulloway (Argyrosomus hololepidotus) (n=6) and manufactured feed
      (n=5) were analysed to benchmark levels of a broad range of residues and
      contaminants of potential public health and trade significance. A subset of these
      samples [YTKF (n=5), Mulloway (n=2) and feed (n=5)] was analysed for dioxins and
      polychlorinated biphenyls (PCBs). The mean concentration of dioxins in YTKF was
      0.6 pg TEQ g(-1) (range 0.22-0.8) and in Mulloway was 0.16 pg TEQ g(-1) (range
      0.16-0.16). The mean concentration of dioxins and dioxin-like PCBs in YTKF was
      2.6 pg TEQ g(-1) (range 1.4-3.5), while Mulloway had a mean concentration of 0.67
      pg TEQ g(-1) (range 0.57-0.76). The mean concentration of PCBs in YTKF was 21 MUg
      kg(-1) (range 8.6-29) and in Mulloway was 5.4 MUg kg(-1) (mean 4.7-6). The mean
      concentration of dioxin-like PCBs in YTKF was 2.1 pg TEQ g(-1) (range 1.2-2.8)
      and in Mulloway was 0.51 pg TEQ g(-1) (range 0.41-0.61). The mean mercury
      concentration in YTKF was 0.03 mg kg(-1) (range 0.02-0.05) and in Mulloway it was
      0.02 mg kg(-1) (range 0.02-0.04). There were no detectable levels of any
      pesticide or antimicrobial compounds in any sample of YTKF or Mulloway. Attention
      is drawn to technical differences in port of entry testing programs such as
      sampling strategies, portion tested, laboratory methodology, residue definitions
      and reporting conventions that exporters' products may be subject to. All
      residues and contaminants were either undetectable or present at very low levels
      when judged against Australian, Japanese and European Union regulatory standards
      (where set).

PMID- 22142629
TI  - Human health risks from mercury exposure from broken compact fluorescent lamps
      (CFLs).
AB  - Human health risk to infants/toddlers and adults was evaluated based on two
      exposure scenarios from compact fluorescent lamp (CFL) breakage; first in a room
      with no ventilation and no clean-up, and second in a room with adequate
      ventilation and clean-up. Concentration data from multiple exposure scenarios
      tested in a study by Stahler et al. (2008) were compared to human toxicity
      benchmarks to calculate hazard quotients. For the no clean-up scenario, hazard
      quotients were generally less than 1, suggesting an unlikely health risk. When
      the room was ventilated and the broken CFL was cleaned-up, mercury concentrations
      were generally lower. A review of release scenarios, along with duration-adjusted
      toxicity benchmarks, indicated that few releases produced levels of concern, but
      some scenarios resulted in exceedance of risk targets and require further study.
      Uncertainties in this screening characterization include assumptions about room
      size, ventilation, age of lamp, the distribution of mercury in the room, and also
      the choice of the toxicity benchmarks used to develop the hazard quotients.

PMID- 22142630
TI  - Design and chemical evaluation of reduced machine-yield cigarettes.
AB  - Experimental cigarettes (ECs) were made by combining technological applications
      that individually reduce the machine measured yields of specific toxicants or
      groups of toxicants in mainstream smoke (MS). Two tobacco blends, featuring a
      tobacco substitute sheet or a tobacco blend treatment, were combined with filters
      containing an amine functionalised resin (CR20L) and/or a polymer-derived, high
      activity carbon adsorbent to generate three ECs with the potential for generating
      lower smoke toxicant yields than conventional cigarettes. MS yields of smoke
      constituents were determined under 4 different smoking machine conditions. Health
      Canada Intense (HCI) machine smoking conditions gave the highest MS yields for
      nicotine-free dry particulate matter and for most smoke constituents measured.
      Toxicant yields from the ECs were compared with those from two commercial
      comparator cigarettes, three scientific control cigarettes measured
      contemporaneously and with published data on 120 commercial cigarettes. The ECs
      were found to generate some of the lowest machine yields of toxicants from
      cigarettes for which published HCI smoke chemistry data are available; these
      comparisons therefore confirm that ECs with reduced MS machine toxicant yields
      compared to commercial cigarettes can be produced. The results encourage further
      work examining human exposure to toxicants from these cigarettes, including human
      biomarker studies.

PMID- 22142632
TI  - The physical and mathematical aspects of inverse problems in radiation detection
      and applications.
AB  - The inverse problem is the problem of converting detectable measurements into
      useful quantifiable indications. It is the problem of spectrum unfolding, image
      reconstruction, identifying a threat material, or devising a radiotherapy plan.
      The solution of an inverse problem requires a forward model that relates the
      quantities of interest to measurements. This paper explores the physical issues
      associated with formulating a radiation-transport forward model best suited for
      inversion, and the mathematical challenges associated with the solution of the
      corresponding inverse problem.

PMID- 22142631
TI  - The role of stem cells in the treatment of diabetic foot ulcers.
AB  - Diabetic foot ulcers (DFUs) are a significant and rapidly growing complication of
      diabetes and its effects on wound healing. Over half of diabetic patients who
      develop a single ulcer will subsequently develop another ulcer of which the
      majority will become chronic non-healing ulcers. One-third will progress to lower
      extremity amputation. Over the past decade, the outcomes for patients with DFUs
      ulcers have not improved, despite advances in wound care. Successful treatment of
      diabetic foot ulcers is hindered by the lack of targeted therapy that hones in on
      the healing processes dysregulated by diabetes. Stem cells are a promising
      treatment for DFUs as they are capable of targeting, as well as bypassing, the
      underlying abnormal healing mechanisms and deranged cell signaling in diabetic
      wounds and promote healing. This review will focus on existing stem cell
      technologies and their application in the treatment of DFUs.

PMID- 22142633
TI  - Development of a large scale production of 67Cu from 68Zn at the high energy
      proton accelerator: closing the 68Zn cycle.
AB  - A number of research irradiations of (68)Zn was carried out at Brookhaven Linac
      Isotope Producer aiming to develop a practical approach to produce the
      radioisotope (67)Cu through the high energy (68)Zn(p,2p)(67)Cu reaction. Disks of
      enriched zinc were prepared by electrodeposition of (68)Zn on aluminum or
      titanium substrate and isolated in the aluminum capsule for irradition.
      Irradiations were carried out with 128, 105 and 92 MeV protons for at least 24h.
      After irradiation the disk was chemically processed to measure production yield
      and specific activity of (67)Cu and to reclaim the target material. The recovered
      (68)Zn was irradiated and processed again. The chemical procedure comprised
      BioRad cation exchange, Chelex-100 and anion exchange columns. Reduction of the
      oxidation degree of copper allowed for more efficient Cu/Co/Zn separation on the
      anion exchange column. No radionuclides other than copper isotopes were detected
      in the final product. The chemical yield of (67)Cu reached 92-95% under remote
      handling conditions in a hot box. Production yield of (67)Cu averaged 29.2
      MUCi/[MUA-h*g (68)Zn] (1.08MBq/[MUA-h*g (68)Zn]) in 24h irradiations. The best
      specific activity achieved was 18.6 mCi/MUg (688.2 MBq/MUg).

PMID- 22142635
TI  - Applications of atomic force microscopy for the assessment of nanoscale
      morphological and mechanical properties of bone.
AB  - Scanning probe microscopy (SPM) has been in use for 30 years, and the form of SPM
      known as atomic force microscopy (AFM) has been around for 25 of those years. AFM
      has been used to produce high resolution images of a variety of samples ranging
      from DNA to carbon nanotubes. Type I collagen and many collagen-based tissues
      (including dentin, tendon, cartilage, skin, fascia, vocal cords, and cornea) have
      been studied with AFM, but comparatively few studies of bone have been
      undertaken. The purpose of this review is to introduce the general principles of
      AFM operation, demonstrate what AFM has been used for in bone research, and
      discuss the new directions that this technique can take the study of bone at the
      nanoscale.

PMID- 22142634
TI  - GSK-3 inhibition by an orally active small molecule increases bone mass in rats.
AB  - Glycogen synthase kinase 3beta (GSK-3beta) actions are central in the canonical
      Wnt pathway, important in many biological processes and a potential drug target
      for treating several diseases. It is appreciated that a balanced Wnt canonical
      signaling is crucial for the maintenance of normal bone mass. In this study we
      investigated the effects of a potent orally active GSK-3 inhibitor, AZD2858, on
      bone mass in rats. Treatment (1 MUM) of human osteoblast cells with AZD2858 in
      vitro increased beta-catenin levels after a short period of time. In rats, oral
      AZD2858 treatment caused a dose-dependent increase in trabecular bone mass
      compared to control after a two-week treatment with a maximum effect at a dose of
      20 mg/kg once daily (total BMC: 172% of control; p<0.001). A small but
      significant effect was also seen at cortical sites (total BMC: 111% of control;
      p<0.001). Biomechanical testing demonstrated an increase in both vertebral
      compression strength at a dose of 20 mg/kg once daily (Load at failure: 370% of
      control, p<0.001) and diaphyseal strength of femora subjected to a three point
      bending test (Load at failure: 115% of control; p<0.01). Furthermore,
      histomorphometry showed a dramatic increase in bone formation indices, and serum
      markers of both bone formation (Osteocalcin, 146% of control; p<0.001) and
      resorption (CTX, 189% of control; p<0.001) were elevated. Our conclusion is that
      a GSK-3 inhibitor drug may prove effective as an anabolic strategy in the
      treatment of diseases characterized by low bone mass, since AZD2858 has extensive
      bone building effects at predominantly trabecular sites.

PMID- 22142636
TI  - Is chronic severe anemia an independent predictor of poor outcomes?

PMID- 22142637
TI  - Primary extragonadal germinoma of the medulla oblongata.
AB  - Extragonadal germ cell tumors rarely arise from the brain stem. In this report,
      the authors present a rare case of germinoma developing in the medulla oblongata.
      A 31-year-old woman complained of intractable hiccups, hoarseness, and swallowing
      disturbance. Magnetic resonance imaging showed a tumor located on the dorsal part
      of the medulla oblongata without any abnormalities in the pineal body and
      suprasellar regions. Histological diagnosis of surgically resected tumor was
      germinoma. Tumor cells were positive for alkaline phosphatase, c-kit, octamer
      binding transcription factor 3/4, cytokeratin, and epithelial membrane antigen in
      immunohistochemistry. The patient received adjuvant chemotherapy and irradiation
      to the residual tumor and cerebral ventricles. The patient is alive without
      recurrence 6 months after the surgery.

PMID- 22142638
TI  - Collision tumor of the stomach: an unusual combination of adenocarcinoma and
      immature "neuroepitheliomatous" teratoma.
AB  - A 54-year-old woman was diagnosed with an asymptomatic gastric tumor during
      routine radiological investigation for staging of breast carcinoma. Subsequent
      endoscopic biopsy confirmed a poorly differentiated adenocarcinoma. Surgical
      resection of the stomach showed a tumor with 2 distinct components: a superficial
      lymphoepithelioma-like adenocarcinoma and a deeper submucosal component
      consistent with immature teratoma. There was lymph node metastasis. The patient
      is well without any evidence of disease 18 months post surgery.

PMID- 22142639
TI  - Benign ganglion cells "invasion" in prostate needle biopsy.

PMID- 22142640
TI  - Changes of body mass index among young men in Brazil over two decades.
AB  - AIM: To evaluate changes in the body mass index (BMI) of young Brazilian men in
      two regions of Brazil at opposing socioeconomic extremes in order to determine
      whether the changes in BMI distribution had different patterns over two decades.
      METHODS: We selected a sample of 6,706,386 males as the study population, aged 18
      years, from individuals that were conscripted into the army from 1980 to 2005.
      The percentiles of the BMI distribution from 1980 to 2005 were calculated. For
      each percentile, the slope of a linear regression curve was tested for increases
      or decreases over time (p < 0.05). RESULTS: The secular trends in BMI showed the
      largest increases at the upper ends of the distributions. However, the lower
      values of the percentiles in both regions did not change over time. The 10th
      percentile for the southeast region and the 20th percentile in the northeast did
      not change. CONCLUSION: No significant differences in the lower percentile values
      were found for the BMI distribution of young Brazilian males during the period
      1980-2005, suggesting that around 10% of young Brazilian males living in the most
      developed regions, such as the southeast, are protected against obesity.

PMID- 22142641
TI  - Detection and mass spectrometric characterization of novel long-term
      dehydrochloromethyltestosterone metabolites in human urine.
AB  - The biotransformation of dehydrochloromethyltestosterone (DHCMT, 4-chloro-17beta
      hydroxy,17alpha-methylandrosta-1,4-dien-3-one) in man was studied with the aim to
      discover long-term metabolites valuable for the antidoping analysis. Having
      applied a high performance liquid chromatography for the fractionation of urinary
      extract obtained from the pool of several DHCMT positive urines, about 50
      metabolites were found. Most of these metabolites were included in the GC-MS/MS
      screening method, which was subsequently applied to analyze the post
      administration and routine doping control samples. As a result of this study, 6
      new long-term metabolites were identified tentatively characterized using GC-MS
      and GC-MS/MS as 4-chloro-17alpha-methyl-5beta-androstan-3alpha,16,17beta-triol
      (M1), 4-chloro-18-nor-17beta-hydroxymethyl,17alpha-methyl-5beta-androsta-1,13
      dien-3alpha-ol (M2), 4-chloro-18-nor-17beta-hydroxymethyl,17alpha-methyl-5beta
      androst-13-en-3alpha-ol (M3), its epimer 4-chloro-18-nor-17alpha
      hydroxymethyl,17beta-methyl-5beta-androst-13-en-3alpha-ol, 4-chloro-18-nor-17beta
      hydroxymethyl,17alpha-methylandrosta-4,13-dien-3alpha-ol (M4) and its epimer 4
      chloro-18-nor-17alpha-hydroxymethyl,17beta-methylandrosta-4,13-dien-3alpha-ol.
      The most long-term metabolite M3 was shown to be superior in the majority of
      cases to the other known DHCMT metabolites, such as 4-chloro-18-nor-17beta
      hydroxymethyl,17alpha-methylandrosta-1,4,13-trien-3-one and 4-chloro
      3alpha,6beta,17beta-trihydroxy-17alpha-methyl-5beta-androst-1-en-16-one.

PMID- 22142642
TI  - Outbreak of hepatitis A in an extended family after importation by non-immune
      travellers.
AB  - The incidence of hepatitis A in England has declined in recent years, but travel
      related cases and imported infections remain a challenge. We report an outbreak
      of hepatitis A in an extended family where two primary cases were infected while
      in Pakistan and two secondary cases were infected in England. All four were
      infected by the same genotype IIIA virus. Testing of the children in the extended
      family by dried blood spots (DBS) determined that three had evidence of recent
      past infections (anti-HAV IgM positive), one had a current asymptomatic infection
      (anti-HAV IgM and HAV RNA positive) and one was incubating the virus (anti-HAV
      IgM negative, HAV RNA positive). HAV RNA from the DBS was identical to the adult
      cases. This outbreak demonstrates secondary spread of hepatitis A by asymptomatic
      children after importation from abroad and highlights the importance of
      preventing travel-associated hepatitis A infection.

PMID- 22142643
TI  - Magnetic resonance microscopy.

PMID- 22142644
TI  - On the therapy effect for a stochastic growth Gompertz-type model.
AB  - We consider a diffusion model based on a generalized Gompertz deterministic
      growth in which carrying capacity depends on the initial size of the population.
      The drift of the resulting process is then modified by introducing a time
      dependent function, called "therapy", in order to model the effect of an
      exogenous factor. The transition probability density function and the related
      moments for the proposed process are obtained. A study of the influence of the
      therapy on several characteristics of the model is performed. The first-passage
      time problem through time-dependent boundaries is also analyzed. Finally, an
      application to real data concerning a rabbit population subject to particular
      therapies is presented.

PMID- 22142645
TI  - Seasonal factors influencing in chemical composition of total suspended particles
      at Pune, India.
AB  - A study on the chemical characterization of boundary layer aerosols is made based
      on the collection of TSP and size separated aerosol mass samples at Pune during
      March 2007-February 2008. This study will be helpful in simulating atmospheric
      processes responsible for aerosol development over Pune region and understanding
      its environmental implications related to radiation budget and climate. It is
      found that major fraction of Ca(2+) is locally generated by suspension of soil
      dust during all the seasons. During pre-monsoon season, coarse Mg(2+) is
      originated from the soil and the sea salt, whereas fine Mg(2+) is generated from
      the local biomass burning. Sizeable amount of SO(4)(2-) is emitted from local
      industrial and brick kiln's activities. Neutralization of NO(3)(-), generated
      both from biogenic and anthropogenic sources, is made by NH(3) gas generated
      mainly from anthropogenic sources. The data are further examined in terms of the
      factors specific to the individual seasons influencing physical and chemical
      characteristics of the boundary layer aerosols. The specific factors are: (a)
      Intense local convection during pre-monsoon season; (b) southwesterly wind flow
      and rainfall activity during monsoon season; and (c) Day time convection and
      occurrence of low level inversion during post-monsoon and winter seasons.

PMID- 22142646
TI  - High levels of uranium in groundwater of Ulaanbaatar, Mongolia.
AB  - Water samples collected from 129 wells in seven of the nine sub-divisions of
      Ulaanbaatar were analyzed by inductively coupled plasma mass spectrometry (ICP
      MS) using Clean Lab methods. The levels of many trace elements were found to be
      low with the average concentrations (ranges in brackets) being 0.9 (<0.1-7.9)
      MUg/L for As; 7.7 (0.12-177) MUg/L for Mn; 0.2 (<0.05-1.9)MUg/L for Co; 16 (<0.1
      686) MUg/L for Zn; 0.7 (<0.1-1.8) MUg/L for Se; <0.1 (<0.02-0.69) MUg/L for Cd;
      and 1.3 (<0.02-32) MUg/L for Pb. The levels of uranium were surprisingly elevated
      (mean, 4.6 MUg/L; range <0.01-57 MUg/L), with the values for many samples
      exceeding the World Health Organization's guideline of 15 MUg/L for uranium in
      drinking water. Local rocks and soils appear to be the natural source of the
      uranium. The levels of uranium in Ulaanbaatar's groundwater are in the range that
      has been associated with nephrotoxicity, high blood pressure, bone dysfunction
      and likely reproductive impairment in human populations. We consider the risk
      associated with drinking the groundwater with elevated levels of uranium in
      Ulaanbaatar to be a matter for some public health concern and conclude that the
      paucity of data on chronic effects of low level exposure is a risk factor for
      continuing the injury to many people in this city.

PMID- 22142647
TI  - Selection of representative emerging micropollutants for drinking water treatment
      studies: a systematic approach.
AB  - Micropollutants remain of concern in drinking water, and there is a broad
      interest in the ability of different treatment processes to remove these
      compounds. To gain a better understanding of treatment effectiveness for
      structurally diverse compounds and to be cost effective, it is necessary to
      select a small set of representative micropollutants for experimental studies.
      Unlike other approaches to-date, in this research micropollutants were
      systematically selected based solely on their physico-chemical and structural
      properties that are important in individual water treatment processes. This was
      accomplished by linking underlying principles of treatment processes such as
      coagulation/flocculation, oxidation, activated carbon adsorption, and membrane
      filtration to compound characteristics and corresponding molecular descriptors. A
      systematic statistical approach not commonly used in water treatment was then
      applied to a compound pool of 182 micropollutants (identified from the
      literature) and their relevant calculated molecular descriptors. Principal
      component analysis (PCA) was used to summarize the information residing in this
      large dataset. D-optimal onion design was then applied to the PCA results to
      select structurally representative compounds that could be used in experimental
      treatment studies. To demonstrate the applicability and flexibility of this
      selection approach, two sets of 22 representative micropollutants are presented.
      Compounds in the first set are representative when studying a range of water
      treatment processes (coagulation/flocculation, oxidation, activated carbon
      adsorption, and membrane filtration), whereas the second set shows representative
      compounds for ozonation and advanced oxidation studies. Overall, selected
      micropollutants in both lists are structurally diverse, have wide-ranging physico
      chemical properties and cover a large spectrum of applications. The systematic
      compound selection approach presented here can also be adjusted to fit individual
      research needs with respect to type of micropollutants, treatment processes and
      number of compounds selected.

PMID- 22142649
TI  - Environmental lead exposure and socio-behavioural adjustment in the early teens:
      the birth to twenty cohort.
AB  - Lead exposure remains high in South Africa. Environmental lead exposure has been
      associated with behaviour problems in childhood and adolescence. The objective of
      this study was to determine the relationship between blood lead levels and socio
      behavioural problems among young adolescents in the Birth to Twenty cohort
      (Bt20). The uniquely South African Bt20 cohort started in 1989 and is a long-term
      prospective follow-up study of the health and well-being of children born in the
      Greater Johannesburg area. The total analytical sample size consisted of 1041
      adolescents (487 males and 554 females). Blood lead levels were obtained from
      whole venous blood that was collected. Thirty two items representing Rule
      breaking and Aggressive behavioural characteristics from the Youth Self Report
      (YSR) were assessed. Bivariate and multiple regression analyses were conducted to
      assess for associations between blood lead levels and socio-behavioural problems
      at 13 years of age. The geometric mean blood lead level was significantly (P
      value < 0.001) higher in boys (6.0 MUg/dl) compared to girls (4.5 MUg/dl). In the
      total analytical sample four behavioural items were significantly associated with
      the geometric mean blood lead levels. When stratifying the sample by sex, the
      bivariate analyses showed that boys' blood lead levels were significantly
      associated with four types of aggressive behaviour. There were no significant
      associations found in girls. The multivariate analysis was conducted in the boys
      sample and after adjusting for socio-economic factors "Attacking People" remained
      significantly associated with blood lead levels. High blood lead levels are
      associated with anti-social and destructive behaviour amongst boys in their early
      teens. However, the relationships are complex and confounded by other aspects of
      adversity.

PMID- 22142648
TI  - Effects of UV irradiation and UV/chlorine co-exposure on natural organic matter
      in water.
AB  - The effects of co-exposure to ultraviolet (UV) irradiation (with either low- or
      medium-pressure UV lamps) and free chlorine (chloramine) at practical relevant
      conditions on changes in natural organic matter (NOM) properties were
      investigated using four waters. The changes were characterized using the specific
      disinfection by-product formation potential (SDBPFP), specific total organic
      halogen formation potential (STOXFP), differential UV absorbance (?UVA), and size
      exclusion chromatography (SEC). The results for exposure to UV irradiation alone
      and for samples with no exposure were also obtained. The SDBPFPs in all UV
      irradiated NOM waters observed were higher than those of non-irradiated samples.
      UV irradiation led to increases in STOXFPs as a result of chlorination, but no
      changes, or only small decreases, from chloramination. UV irradiation alone led
      to positive ?UVA spectra of the four NOM waters; co-exposure to UV and chlorine
      gave larger negative ?UVA spectra than those obtained by chlorine exposure alone.
      No obvious changes in SEC results were observed for samples only irradiated with
      UV light; co-exposure gave no detectable changes in the abundances of small
      fractions for exposure to chlorine only. Both UV photooxidation and
      photocatalytic oxidation appear to affect the reactivity of the NOM toward
      subsequent chlorination, and the magnitude of the changes is generally greater
      for medium-pressure lamps than for low-pressure lamps. These results suggest that
      applying UV disinfection technology to a particular source may not always be
      disinfection by-product-problem-free, and the interactions between UV light,
      chlorine, and NOM may need to be considered.

PMID- 22142650
TI  - Residential proximity to major roads and placenta/birth weight ratio.
AB  - Exposure to air pollution has been demonstrated to increase the risk of preterm
      birth and low birth weight. We examined whether proximity to major roads (as a
      marker of exposure to air pollution) is associated with increased placenta/birth
      weight ratio (as a biomarker of the placental transport function). Data on
      parental characteristics and birth outcomes were extracted from the database
      maintained by a major hospital in Shizuoka Prefecture, Japan. We restricted the
      analysis to mothers who delivered liveborn single births from 1997 to 2008 (n =
      14,189). Using geocoded residential information, each birth was classified
      according to proximity to major roads. We examined the association between
      proximity to major roads and the placenta/birth weight ratio, using multiple
      linear regression. Proximity to major roads was associated with higher
      placenta/birth weight ratio. After adjusting for potential confounders, living
      within 200 m of a major road increased the ratio by 0.48% (95% CI = 0.15 to 0.
      80). In addition, proximity to major roads was associated with lower placenta
      weight and birth weight. These observed associations were stronger among
      participants living closer to major roads. Exposure to traffic-related air
      pollution is associated with higher placenta/birth weight ratio. Impaired
      placental oxygen and nutrient transport function might be a mechanism for
      explaining the observed association between air pollution and low birth weight as
      well as preterm birth.

PMID- 22142651
TI  - Rapid improvement of depression and quality of life with escitalopram treatment
      in outpatients with breast cancer: a 12-week, open-label prospective trial.
AB  - BACKGROUND: Among patients with cancer, the management of depression is very
      important to improve quality of life as well as distress. Because the efficacy of
      escitalopram, a potent serotonin reuptake inhibitor, has not been well evaluated
      in cancer patients, we investigated its effects on depression and quality of life
      in outpatients with breast cancer. METHODS: A 12-week, open-label, prospective
      study with escitalopram (5-20mg/day) was performed in 79 breast cancer
      outpatients with depression. The primary outcome was measured using the Hamilton
      Depression Rating Scale (HAMD), which was administered at baseline, 1, 2, 4, 8,
      and 12 weeks after treatment. The Functional Assessment of Cancer Therapy-Breast
      (FACT-B), MD Anderson Symptoms Inventory (MDASI), Clinical Global Impression
      Severity of Illness (CGI-S), and Distress Thermometer (DT) were also used to
      measure improvement in symptoms, distress, and quality of life. RESULTS: Compared
      to baseline, HAMD, DT, and CGI-S scores were significantly decreased at week 1
      and onwards, and FACT-B and MDSAI were improved at week 2 and onwards. At the end
      point (week 12), all FACT-B subscales including the physical, emotional,
      social/family, functional well-being, and the breast cancer subscales were
      improved. Improvement in distress and quality of life was associated with a
      reduction in depressive symptoms. Of all participants, 45.1% met the response
      criterion (at least a 50% decrease in HAMD total score), and 30.6% met the
      remission criterion (HAMD total score <= 7) at week 12. CONCLUSIONS: In the
      present study, escitalopram improved quality of life and reduced depression in
      breast cancer patients. Symptoms rapidly improved within 1 week, influencing
      quality of life. Escitalopram may be an effective treatment of depressive
      symptoms in breast cancer patients.

PMID- 22142652
TI  - 'iReconstruct': clinically relevant plastic surgery apps.

PMID- 22142653
TI  - Clinicopathological consistency in skin disorders: a retrospective study of 3949
      pathological reports.
AB  - BACKGROUND: Although the clinicopathological approach plays an important role in
      skin disorder diagnoses, few studies have evaluated the consistency between
      clinical and histopathological diagnoses of skin disorders. OBJECTIVE: We sought
      to investigate the consistency, and factors affecting consistency, between
      clinical diagnoses and pathological diagnoses in patients with skin disorders
      referred for biopsy by dermatologists. METHODS: We retrospectively examined 3949
      pathological reports of biopsy specimens, between 1999 and 2008. The
      relationships between clinical and pathological diagnoses were studied in 4
      groups, namely: (1) definite pathological diagnoses consistent with the clinical
      diagnoses, (2) descriptive pathological diagnoses consistent with the clinical
      diagnoses, (3) definite pathological diagnoses inconsistent with the clinical
      diagnoses, and (4) descriptive pathological diagnoses inconsistent with the
      clinical diagnoses. The first two groups show consistency, whereas the latter two
      groups show inconsistency between the diagnoses. RESULTS: The pathological
      diagnoses were consistent with the clinical diagnoses in 3034 biopsy reports
      (76.8%), and they were inconsistent in 915 reports (23.2%). In all types of skin
      disorders, clinicopathological consistency was higher in patients with sufficient
      clinical descriptive information. No correlation was observed between
      clinicopathological consistency and biopsy type, number of clinical diagnoses, or
      specifying the location of disease. Disease duration was shorter in the biopsy
      reports showing clinicopathological consistency. Moreover, a statistically
      significant increase was found in clinicopathological consistency for
      inflammatory dermatoses, when pathologists evaluated the specimens with clinical
      diagnoses, in comparison with blind evaluation. LIMITATIONS: The retrospective
      nature of the study might have resulted in a loss of data. CONCLUSION: In a
      dermatology clinic setting, providing sufficient clinical descriptive information
      for pathology requisition forms increases the probability of making an accurate
      diagnosis.

PMID- 22142654
TI  - Balanced vs unbalanced crystalloid resuscitation in a near-fatal model of
      hemorrhagic shock and the effects on renal oxygenation, oxidative stress, and
      inflammation.
AB  - BACKGROUND: The aim of the present study was to test the hypothesis that balanced
      crystalloid resuscitation would be better for the kidney than unbalanced
      crystalloid resuscitation in a rat hemorrhagic shock model. METHODS: Male Wistar
      rats were randomly assigned to four groups (n=6/group): (1) time control; (2)
      hemorrhagic shock control; (3) hemorrhagic shock followed by unbalanced
      crystalloid resuscitation (0.9% NaCl); and (4) hemorrhagic shock followed by
      acetate and gluconate-balanced crystalloid resuscitation (Plasma Lyte). We tested
      the solutions for their effects on renal hemodynamics and microvascular
      oxygenation, strong-ion difference, systemic and renal markers of inflammation
      and oxidative stress including glycocalyx degradation as well as their effects on
      renal function. RESULTS: The main findings of our study were that: (1) both the
      balanced and unbalanced crystalloid solutions successfully restored the blood
      pressure, but renal blood flow was only recovered by the balanced solution
      although this did not lead to improved renal microvascular oxygenation; (2) while
      unbalanced crystalloid resuscitation induced hyperchloremia and worsened
      metabolic acidosis in hemorrhaged rats, balanced crystalloid resuscitation
      prevented hyperchloremia, restored the acid-base balance, and preserved the anion
      gap and strong ion difference in these animals; (3) in addition balanced
      crystalloid resuscitation significantly improved renal oxygen consumption
      (increased VO(2), decreased  [Formula: see text] ); and (4) however neither
      balanced nor unbalanced crystalloid resuscitation could normalize systemic
      inflammation or oxidative stress. Functional immunohistochemistry biomarkers
      showed improvement in L-FABP in favor of balanced solutions in comparison to the
      hemorrhagic group although no such benefit was seen for renal tubular injury
      (measured by NGAL) by giving either unbalanced or balanced solutions.
      CONCLUSIONS: Although balanced crystalloid resuscitation seems superior to
      balanced crystalloid resuscitation in protecting the kidney after hemorrhagic
      shock and is certainly better than not applying fluid resuscitation, these
      solutions were not able to correct systemic inflammation or oxidative stress
      associated with hemorrhagic shock.

PMID- 22142655
TI  - Do bulb syringes conform to neonatal resuscitation guidelines?
AB  - OBJECTIVE: To reduce airway injury secondary to high suction pressures, the
      American Academy of Pediatrics Neonatal Resuscitation Program (NPR) recommends
      that suction pressures be less than 100 mm Hg. This study was conducted to
      determine if suction bulbs conform to these recommendations. STUDY DESIGN: In
      this prospective in vitro study, 25 personnel involved in neonatal resuscitation
      squeezed a new bulb three times for each of six commercially available bulbs
      using their delivery suite technique. A calibrated, pneumatic transducer measured
      the pressure of each squeeze. RESULTS: Only one bulb met the NRP guidelines with
      none of the participants exceeding 100mm Hg (p<0.001). CONCLUSIONS: Only one bulb
      met the NRP guidelines of generating pressures less than 100 mm Hg. This bulb's
      large size (3 oz) may preclude its use in premature infants. Individuals involved
      in resuscitating newborns need to be aware of the pressures generated to avoid
      injuring the delicate oral airway.

PMID- 22142656
TI  - Management of hepatocellular carcinoma with transarterial chemoembolization in
      the era of systemic targeted therapy.
AB  - The clinical management of hepatocellular carcinoma (HCC) is often complicated by
      poor liver function. Treatment options for intermediate- and advanced-stage
      disease are limited. Transcatheter arterial chemoembolization (TACE) is an
      effective first-line therapy for intermediate-stage HCC. By interrupting blood
      flow to the tumor and administering concentrated chemotherapy locoregionally,
      TACE induces necrosis at the tumor site, but may create conditions that permit or
      encourage angiogenesis and recurrence of the tumor. Combination of TACE with new
      targeted agents may be an effective way to treat intermediate-stage HCC,
      particularly in higher risk patients. Because of the efficacy and safety of
      sorafenib-the first systemic therapy to show significant clinical benefit in
      advanced HCC-there is great interest in its potential use in combination with
      existing treatment modalities. The synergistic combination of TACE plus sorafenib
      represents a promising opportunity for tumor control.

PMID- 22142657
TI  - Factors associated with fluoride concentrations in whole and parotid ductal
      saliva.
AB  - BACKGROUND/AIMS: There are still uncertainties regarding the use of whole and
      parotid ductal saliva as indicators of chronic exposure to fluoride. This study
      evaluated the effect of water fluoride concentration, age, gender, geographical
      area and localization (urban/rural) on fluoride concentrations in whole and
      ductal saliva. METHODS: Subjects (n = 300) aged 3-7, 14-20, 30-40 and 50-60
      years, from five communities (A-E) with different fluoride concentrations in the
      drinking water, participated in the study. Two samples of drinking water and
      parotid and whole saliva were collected for each subject and were analyzed for
      fluoride using appropriate electrode techniques. RESULTS: Mean water F
      concentrations (+/-SE, mg/l, n = 60) were 0.09 +/- 0.01, 0.15 +/- 0.01, 0.66 +/-
      0.01, 0.72 +/- 0.02, and 1.68 +/- 0.08 for A-E, respectively. Mean F
      concentrations (+/-SE, mg/l, n = 15) ranged between 0.014 +/- 0.002 (A, 3-7
      years) and 0.297 +/- 0.057 (D, 14-20 years) for whole saliva and 0.009 +/- 0.001
      (C, 30-40 years) and 0.284 +/- 0.038 (E, 50-60 years) for parotid saliva. Results
      of multivariate linear regression analysis showed that geographical area and
      water fluoride concentration exerted the strongest influence in whole and ductal
      saliva F concentrations, respectively. CONCLUSION: Therefore, parotid ductal
      saliva seems to be a more appropriate biomarker of fluoride exposure, and factors
      like age and localization should also be considered when using this biomarker.

PMID- 22142658
TI  - Monitoring of autophagy in Chinese hamster ovary cells using flow cytometry.
AB  - Recently, autophagy, which is a degradative process, has drawn attention as an
      anti-cell death engineering target in addition to apoptosis in recombinant
      Chinese hamster ovary (rCHO) cell cultures for enhanced production of therapeutic
      proteins. Appropriate autophagy monitoring methods, that are suitable for long
      term CHO cell cultures, are necessary in order to investigate the culture
      conditions that affect the autophagy pathway and to select appropriate
      engineering targets for autophagy control. Herein, detailed protocols for
      autophagy monitoring methods based on flow cytometry are provided using the GFP
      LC3-overexpressing CHO DG44 host cell line or MDC-like molecules in rCHO cells
      grown as an adherent culture with serum-containing medium or suspension culture
      with serum-free medium. Furthermore, combined with the apoptosis detection based
      on the Annexin V-PS interaction, the simultaneous detection of autophagy and
      apoptosis is also described. It is anticipated that the protocols described
      herein will assist in the fast, high throughput monitoring of autophagy that can
      support other existing autophagy assays.

PMID- 22142659
TI  - Emerging role for bisphosphonates in cancer management.

PMID- 22142661
TI  - Bisphosphonates and their impact on disseminated tumor cells in early stage
      breast cancer.
AB  - Bone is the most common site of relapse in breast cancer. Unlike many other
      malignancies, breast cancer is often associated with late-onset metastases, most
      commonly seen in bone and soft tissue. Pre-clinical and clinical evidence suggest
      that micrometastases occur at a very early stage of cancer development but do not
      become overt metastases until a later time when the microenvironment is more
      suitable. Bisphosphonates (BPs), especially zoledronic acid (ZOL), decrease bone
      resorption by suppressing the activity of osteoclasts and are used to prevent
      further bone loss in patients with osteoporosis. In addition, pre-clinical and
      clinical evidence suggest that potent BPs have direct and/or indirect anti-tumor
      effects, through induction of apoptosis, inhibition of invasion and metastases as
      well as angiogenesis, and through alteration of the immune system. ZOL is
      approved for the treatment of metastatic cancer to bone, and has been shown to
      prevent skeletal related events and reduce associated pain, without a clear
      impact on survival. Several large clinical trials (ABSCG 12, ZO-FAST and AZURE)
      have studied the direct anti-tumor effect of BPs in early stage breast cancer.
      The results are controversial, suggesting that ZOL may have benefits in specific
      settings. Targeting patients at particularly high risk for relapse, and
      identifying surrogate markers of BP effect is clearly a critical component
      necessary to understand the anti-tumor effect of these agents. Disseminated tumor
      cells (DTCs) are surrogate markers that have been correlated with an increased
      risk of recurrence in patients with early stage breast cancer. Several studies
      have either used the presence of DTCs to assess risk and determine eligibility
      for BP treatment, or have used DTCs as a surrogate marker of BP anti-tumor
      effect. This review summarizes the pre-clinical data supporting anti-tumor
      effects of BPs as well as their impact on DTCs in clinical studies. New
      candidates for bone-targeted therapy are briefly discussed.

PMID- 22142660
TI  - Bisphosphonates and breast cancer incidence and recurrence.
AB  - Bisphosphonates are commonly used in patients with breast cancer to reduce
      skeletal-related events in metastatic disease and to mitigate bone loss
      associated with adjuvant therapy. Preclinical studies have shown that
      bisphosphonates may directly inhibit breast cancer cell proliferation and
      metastasis. Clinical trials evaluating the oral bisphosphonate clodronate as a
      component of adjuvant therapy identified a potential reduction in cancer
      recurrence. Subsequently, trials of zoledronic acid have demonstrated prolonged
      disease-free survival in postmenopausal or otherwise estrogen-depleted women with
      early breast cancer. In the ABCSG-12 trial, the addition of twice-yearly
      zoledronic acid (4 mg IV) to adjuvant endocrine therapy improved disease-free
      survival in premenopausal women undergoing ovarian suppression. Similar results
      were observed in postmenopausal women receiving aromatase inhibitors in the ZO
      FAST trial, and in women who were at least 5 years past menopause in the AZURE
      trial. Four recent observational studies (2 cohort studies and 2 case-control
      analyses) generally support an association between oral bisphosphonate use and
      lower breast cancer incidence. Ongoing breast cancer adjuvant clinical trials are
      further evaluating bisphosphonates and, by their influence on contralateral
      cancers, may provide more evidence regarding the potential of bisphosphonates for
      breast cancer prevention.

PMID- 22142663
TI  - Intravenous bisphosphonates for breast cancer: impact on patient outcomes and
      scientific concepts.
AB  - Among women worldwide, breast cancer is the most common malignancy and a leading
      cause of death, accounting for approximately 6% of all cancer deaths globally.
      The predilection of breast cancer to metastasize to bone provides a strong
      rationale that antiresorptive agents such as bisphosphonates may have the
      potential to prevent disease recurrence. Bisphosphonates are established
      therapies for bone loss and for preventing skeletal-related events (SREs) from
      bone metastases. Moreover, intravenous nitrogen-containing bisphosphonates, such
      as zoledronic acid, have been shown to block multiple steps in tumor metastasis
      (e.g., angiogenesis, invasion, and adhesion). Recent clinical data from ABCSG-12,
      ZO-FAST, and AZURE demonstrate that zoledronic acid can significantly improve
      disease-free survival (DFS) in the adjuvant breast cancer setting in women who
      are naturally postmenopausal or have endocrine therapy-induced menopause.
      Furthermore, the ABCSG-12 trial showed durable disease-free survival benefits 2
      years after completion of adjuvant therapy. These data suggest a potential role
      for zoledronic acid beyond bone health in breast cancer. Although it is too early
      to determine which patients are most likely to benefit from the anticancer
      potential of bisphosphonates, future research will help further guide therapy in
      this setting.

PMID- 22142662
TI  - Clinical profile, BRCA2 expression, and the androgen receptor CAG repeat region
      in Egyptian and Moroccan male breast cancer patients.
AB  - INTRODUCTION: Male breast cancer (MBC) is a rare disease. Rates of MBC in
      Northern Africa vary by region. The age-standardized incidence for MBC is higher
      in Morocco than in Egypt, and the Egyptian rate is similar to the U.S of
      approximately 1/10(5)This study aimed at investigating the clinical and molecular
      characteristics of MBC in Egypt and Morocco. METHODS: This case-case study
      included 211 cases from Egypt and 132 from Morocco. Tumor tissues were available
      for 47 Egyptian and 18 Moroccan patients. Medical record information was
      abstracted for patients' demographics, medical history, and treatment. BRCA2
      protein expression status was examined in Egyptian and Moroccan tumors. Androgen
      receptor CAG repeat length was analyzed using the tissue samples in Egyptian MBC
      tumors and controls. Limited amount of tissues from Morocco did not allow for the
      analysis of CAG repeats. RESULTS: Egyptian MBC patients had a significantly lower
      age at diagnosis (Egypt: 57.5 +/- 15.1, Morocco: 63.9 +/- 14.4, P=0.0002) and a
      higher prevalence of liver cirrhosis (Egypt: 28.0%, Morocco: 0.8%, P=< 0.0001).
      MBC patients also had higher tumor grades [I (0.9%), II (81.0%), III (18.1%)] in
      Egypt vs. [I (10.7%), II (81.0%), III (8.3%)] in Morocco (P=0.0017). The clinical
      and molecular characteristics of the groups from the 2 countries did not
      significantly differ. There was no significant difference with respect to BRCA2
      expression amongst countries (Egypt: 28.9% non-wild type, Morocco: 27.8% non-wild
      type, P=0.9297) or CAG lengths amongst BRCA2 expression types in Egyptians (Wild
      type: 54.6% with CAG repeat lengths of 20+, Non-wild type: 50% with CAG repeat
      lengths of 20+, P=0.7947). CONCLUSIONS: Differences in MBC between Egypt and
      Morocco are more likely due to differences in other risk factors such as
      consanguinity and use of xenoestrogenic pesticides.

PMID- 22142664
TI  - Bone turnover markers: tools for prognosis and monitoring response to
      bisphosphonates?
AB  - Skeletal homeostasis is maintained by spatially coupled and balanced processes of
      osteolysis and osteogenesis. Several factors across the breast cancer continuum
      (e.g., adjuvant therapies, bone metastases in advanced disease) can disrupt this
      balance. Circulating levels of specific biochemical markers released during bone
      turnover provide relatively non-invasive means to assess ongoing rates of
      skeletal metabolism. Such markers may provide insight into the risk of bone loss
      and fractures in women with osteoporosis and during adjuvant therapy for breast
      cancer. In addition, bone marker levels and alterations might reflect tumor-bone
      interactions and response to bisphosphonate treatment in patients with bone
      metastases. Thus far, the largest body of evidence supports a potential role for
      urinary N-terminal cross-linked telopeptide of type I collagen (NTX) in
      predicting risks of skeletal morbidity and death, and monitoring response during
      zoledronic acid treatment, in patients with bone metastases. Other possible
      applications for bone markers include diagnosis of bone metastases and monitoring
      bone disease progression. Ongoing clinical trials evaluating the potential for
      bone marker changes to provide insights into the disease course and response to
      various classes of antiresorptive therapies are expected to expand the role of
      bone markers in the management of patients with breast cancer.

PMID- 22142665
TI  - Projected prevalence of inadequate nutrient intakes in Europe.
AB  - BACKGROUND: The purpose of this study was to analyze the prevalence of nutrient
      intake inadequacy in Europe, applying the Nordic Nutritional Recommendations in
      the context of the EURRECA Network of Excellence. METHODS: Nutrient data was
      obtained from the European Nutrition and Health Report II. Those nutritional
      surveys using a validated food frequency questionnaire or diet history and a food
      diary/ register with at least 7 days of registers or with an adjustment for
      intraindividual variability were included. The nutrients analyzed were: vitamin
      C, vitamin D, vitamin B(12), folic acid, calcium, iron, zinc, selenium, copper,
      and iodine. The estimated average requirement cut point was applied to estimate
      inadequacy. The Nordic and Institute of Medicine nutrient recommendations were
      used as references. RESULTS: The mean prevalence of inadequacy was below 11% for
      zinc, iron, and vitamin B(12) (only in the elderly), and it was 11-20% for copper
      in adults and the elderly and for vitamin B(12) in adults and vitamin C in the
      elderly. The prevalence was above 20% for vitamin D, folic acid, calcium,
      selenium, and iodine in adults and the elderly and for vitamin C in adults.
      CONCLUSIONS: Vitamin C, vitamin D, folic acid, calcium, selenium, and iodine were
      the nutrients showing a higher prevalence of inadequate intakes in Europe.

PMID- 22142666
TI  - Feasibility and accuracy of fall reports in persons with dementia: a prospective
      observational study.
AB  - BACKGROUND: The feasibility, test-retest reliability, and accuracy of different
      fall recording methods have not been studied in older persons with dementia.
      METHODS: This was a prospective observational study, nested within a randomized
      controlled trial on motor training, in which 110 participants were monitored for
      falls over 12 months. Seven methods of fall recording were compared: face-to-face
      interviews; phone interviews: weekly for three months, monthly for 9 months, a
      final interview after 12 months; prospective calendar method; interviews with a
      proxy and the general practitioner (GP). Summing the count of falls and removing
      duplicate reporting of the same fall was found to provide the best approximation
      of the actual number of falls and was chosen as the criterion-standard. RESULTS:
      The combination of calendar method and phone interviews showed the highest
      accuracy (74% of falls, 93% of fallers). As a single measure, weekly phone calls
      were superior to calendars or proxy-report. Monthly phone calls recorded only
      half the falls that were picked up by weekly calls (p = 0.002) and were inferior
      to the calendars (p<0.001) and proxy-report (p = 0.015). GPs knew of only 14% of
      falls and 19% of fallers. In addition, 49% of subjects who documented a fall
      prospectively did not recall a fall after 12 months. CONCLUSION: The combination
      of fall calendars with regular telephone interviews can be recommended for
      persons with mild to moderate stage dementia. If feasible, recall periods should
      be as short as one week; additional information by care-givers increases accuracy
      of reports. Retrospective recall of falling with long recall periods is not
      recommended.

PMID- 22142667
TI  - Facial macrosomatognosia and pain in a case of Wallenberg's syndrome: selective
      effects of vestibular and transcutaneous stimulations.
AB  - Macro- and micro-somatognosia refer to rare disorders of the cerebral
      representation of the body whereby patients perceive body parts as
      disproportionately large or small. Here we report the experimental study of a
      patient who, following a left lateral medullary stroke (Wallenberg's syndrome,
      including vestibular deficits) complained of a persistent somatosensory illusory
      sensation of swelling, confined to the left side of his face (i.e., left
      macrosomatognosia). This hemifacial somatosensory distortion was associated with
      a left facial anesthesia, and a neuropathic pain affecting the three branches of
      the left trigeminal nerve. In this study, we first document quantitatively the
      patient's somatosensory illusion by using a somatosensory-to-visual matching task
      in which the patient modified the picture of his own face to fit his left-sided
      somatosensory misperception. The patient's performance revealed that
      macrosomatognosia was confined to the second branch of the left trigeminal nerve.
      Perception of the size of visual objects was comparatively preserved. Second, we
      investigated the effects of two peripheral stimulations, which may affect the
      spatial component of somatosensory deficits (caloric vestibular stimulation, CVS;
      transcutaneous electrical nervous stimulation, TENS) and pain (TENS). Left CVS
      abolished the facial somatosensory illusion, for about 30min, but had no effect
      on the left facial pain. Conversely, left TENS substantially reduced the
      neuropathic pain during stimulation, but had no effect on macrosomatognosia,
      indicating a double dissociation between the two disorders. These results reveal
      that facial macrosomatognosia may be regarded as a high-order deficit of
      somatosensory perception of the shape and volume of the face, which fits the
      definition of 'hyperschematia' (i.e., when the body takes up too much room)
      originally proposed by Bonnier (1905). Our data also indicate that CVS may favor
      the restoration of the conscious representation of the shape and size of the
      face. Overall, these findings lend support to the view that afferent inputs from
      the vestibular system can affect in a specific fashion the activity of cerebral
      structures involved in the building up and updating of the topological
      description of body parts.

PMID- 22142668
TI  - Aspirin resistance, platelet turnover, and diabetic angiopathy: a 2011 update.
AB  - In 2004 an editorial article on the so-called "aspirin resistance" and diabetic
      angiopathy as related to platelet turnover was published by one of us. An update
      of this issue is now presented. The evidence of an incomplete inhibition of
      platelet function by aspirin, despite doses of the drug proved to be clinically
      effective are employed, was first reported in the '80s, in studies devoted to
      platelet turnover. Based on this concept, the possibility of monitoring the entry
      of newly formed platelets into the circulation after aspirin ingestion was
      documented by measuring the return of thromboxane biosynthesis by platelets
      challenged in vitro by pairs of aggregating agents. The data obtained showed that
      platelets with intact cyclooxygenase activity could be detected into the
      circulation of control individuals as early as 4-6hrs after aspirin ingestion,
      but at shorter time intervals in diabetic angiopathy. In the latter setting, it
      was concluded that "schedules of aspirin which may suffice in normals are not
      effective in patients with diabetic angiopathy, presumably because these patients
      have a high rate of entry of new platelets into the circulation". As many as
      25years after its original publication, the clinical relevance of an accelerated
      platelet turnover as to "aspirin resistance" has been confirmed and extended to
      other clinical settings at high risk of ischemic events. Newer aspirin dosing and
      scheduling, tailored at reducing the individual patient risk related to an
      incomplete inhibition of platelet function by a standard aspirin dose should now
      be defined.

PMID- 22142669
TI  - Mobile phone use for contacting emergency services in life-threatening
      circumstances.
AB  - BACKGROUND: The potential health benefits of mobile phone use have not been
      widely studied, except for telemedicine-type applications. STUDY OBJECTIVES: This
      study seeks to determine whether initial contact with emergency services via a
      mobile phone in life-threatening situations is associated with potential health
      benefits when compared to contact via a landline. METHODS: A record-linkage study
      was carried out in which data from all emergency dispatches for immediately life
      threatening events from a United Kingdom county ambulance service were linked to
      the Patient Admission System at two major local hospitals. Mortality (at the
      scene, at the emergency department [ED], and during hospitalization); transfer to
      the ED; admission (inpatient care, and intensive care unit); and length of stay
      were analyzed for calls classified as Code Red (immediately life-threatening) by
      initial exposure (mobile phone vs. landline), while controlling for potential
      confounding variables. RESULTS: Of 354,199 ambulances dispatched to attend
      emergency incidents, 66% transported patients to the hospital while 2% stood down
      due to death at the scene. Mobile phone compared to landline reporting of
      emergencies resulted in significant reductions in the risk of death at the scene
      (odds ratio [OR] 0.77), but not for death in the ED or during inpatient
      admission. The risk of being transferred to the ED and subsequent inpatient
      admission were significantly lower with reporting from mobile phones compared to
      landline (OR 0.93 and OR 0.82, respectively). CONCLUSIONS: In this study,
      evidence of statistical association was demonstrated between the use of mobile
      phones to alert ambulance services in life-threatening situations and improved
      outcomes for patients.

PMID- 22142670
TI  - Computer access and Internet use by urban and suburban emergency department
      customers.
AB  - BACKGROUND: Patients are increasingly using the Internet (43% in 2000 vs. 70% in
      2006) to obtain health information, but is there a difference in the ability of
      urban and suburban emergency department (ED) customers to access the Internet?
      STUDY OBJECTIVE: To assess computer and Internet resources available to and used
      by people waiting to be seen in an urban ED and a suburban ED. METHODS:
      Individuals waiting in the ED were asked survey questions covering demographics,
      type of insurance, access to a primary care provider, reason for their ED visit,
      computer access, and ability to access the Internet for health-related matters.
      RESULTS: There were 304 individuals who participated, 185 in the urban ED and 119
      in the suburban ED. Urban subjects were more likely than suburban to be women,
      black, have low household income, and were less likely to have insurance. The
      groups were similar in regard to average age, education, and having a primary
      care physician. Suburban respondents were more likely to own a computer, but the
      majority in both groups had access to computers and the Internet. Their frequency
      of accessing the Internet was similar, as were their reasons for using it.
      Individuals from the urban ED were less willing to schedule appointments via the
      Internet but more willing to contact their health care provider via e-mail. The
      groups were equally willing to use the Internet to fill prescriptions and view
      laboratory results. CONCLUSION: Urban and suburban ED customers had similar
      access to the Internet. Both groups were willing to use the Internet to access
      personal health information.

PMID- 22142671
TI  - Simultaneous T-wave inversions in anterior and inferior leads: an uncommon sign
      of pulmonary embolism.
AB  - BACKGROUND: Pulmonary embolism (PE), a major cause of morbidity and mortality,
      remains an elusive diagnosis. Recently investigators have found a new
      electrocardiographic (ECG) finding, simultaneous T-wave inversions in the
      anterior and inferior leads, which may distinguish PE from acute coronary
      syndrome (ACS). OBJECTIVES: Our primary objective was to estimate the prevalence
      of this finding in PE. We also estimate the inter-rater reliability of this
      finding, its test characteristics, and assess ECG findings traditionally
      associated with PE. METHODS: In this unmatched case-control study, we selected
      electrocardiograms from patients diagnosed with PE, ACS, and non-cardiac chest
      pain. Two emergency physicians, blinded to diagnoses, reviewed electrocardiograms
      for explicitly defined ECG findings. We calculated kappa (K) for inter-rater
      agreement and estimated prevalence differences (PD) for findings in the PE group
      vs. pooled control groups. RESULTS: We included 97 patients with PE, 89 with ACS,
      and 105 with non-cardiac chest pain. A 1-mm T-wave inversion was seen in both III
      and V(1) in 11/97 (0.113) of patients with PE vs. 9/194 (0.046) controls (PD 0.07
      [95% confidence interval (CI) -0.01-+0.14]; K = 0.7). Other criteria for anterior
      and inferior T-wave inversions were less common in PE (0.04-0.05). Among several
      other ECG abnormalities tested, only sinus tachycardia (PD 0.20 [95% CI 0.09
      0.31]; K = 0.7) and the classic S(I)Q(III)T(III) pattern (PD 0.05 [95% CI -0.01
      +0.11]; K = 0.5) statistically distinguished PE and were noted with fair or
      better inter-rater agreement. CONCLUSION: In our study, simultaneous T-wave
      inversions in anterior and inferior leads were associated with PE but are seen in
      only 4-11% of cases.

PMID- 22142672
TI  - Succinylcholine-induced hyperkalemia in a patient with multiple sclerosis.
AB  - BACKGROUND: Succinylcholine administration is associated with hyperkalemia in
      patients with a variety of medical conditions, including many neuromuscular
      disorders. Nonetheless, there is a paucity of literature describing hyperkalemia
      after the administration of succinylcholine to patients with multiple sclerosis.
      CASE REPORT: This case report describes a 38-year-old woman with multiple
      sclerosis who developed life-threatening hyperkalemia after the administration of
      succinylcholine during rapid sequence intubation. CONCLUSION: This case
      highlights the potential for iatrogenic hyperkalemia after succinylcholine in
      patients with neurologic diseases, including multiple sclerosis.

PMID- 22142673
TI  - Acute meningitis prognosis using cerebrospinal fluid interleukin-6 levels.
AB  - BACKGROUND: Improved diagnostic tests would aid in diagnosing and treating
      community-acquired meningitis. OBJECTIVE: To analyze the diagnostic value of
      interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of patients presenting with
      symptoms of acute meningitis. MATERIAL AND METHODS: In a 6-month prospective,
      observational, cross-sectional emergency department (ED) study, serum and CSF
      samples were obtained from all patients with a headache and fever in whom the
      physician suspected meningitis. Patients were excluded if computed tomography
      findings contraindicated a lumbar puncture, if they had bleeding disorders, or if
      their serum indicated bleeding. IL-6 levels were measured and compared in
      patients with (Group A) and without (Group B) bacterial meningitis. RESULTS:
      Samples were obtained from 53 patients, of whom 40 were ultimately found to have
      meningitis. These 40 patients averaged 49.6 +/- 21.9 years, with number of men 18
      (45%), hospitalizations 21 (52%), mortality 3 (.07%), and IL-6 average rating 491
      (median: 14.5; range 0000-6000). Findings in the two groups were: Group A (with
      meningitis): n = 13, average IL-6 level: 1495 (median: 604; 25/75 percentiles:
      232.5-2030; 95% confidence interval [CI] 371.7-2618.6; range 64-6000). Group B
      (with aseptic meningitis): n = 27, average IL-6 level: 7.34 (median: 5; 25/75
      percentiles: 0.0/15.1; 95% CI 3.94-10.73; range 0-23.6). Mann-Whitney rank sum
      test: p < 0.0001. CONCLUSIONS: In patients with acute bacterial meningitis, CSF
      cytokine concentrations are elevated. Measuring CSF inflammatory cytokine levels
      in patients with acute meningitis could be a valuable ED diagnostic tool. Using
      this tool could improve the prognosis of patients with bacterial meningitis by
      allowing more rapid initiation of antibiotic treatment.

PMID- 22142674
TI  - Massive pulmonary embolism with acute coronary syndrome-like electrocardiogram
      mimicking acute left main coronary artery obstruction.

PMID- 22142675
TI  - Usefulness of severity scores in patients with suspected infection in the
      emergency department: a systematic review.
AB  - BACKGROUND: Score systems for severity of illness and organ dysfunction have been
      validated and used as tools to predict the risk of death in intensive care unit
      (ICU) patients, but their usefulness in patients with suspected infection in the
      emergency department (ED) or hospital ward is unclear. OBJECTIVES: The objective
      of this systematic review was to establish the accuracy of score systems in the
      prediction of mortality in patients with suspected infection in hospital settings
      compared to the ICU. METHODS: Three researchers independently performed a
      systematic search and a review of related articles and their references using the
      PubMed database. The articles were selected by consensus, based on previously
      defined inclusion and exclusion criteria. RESULTS: In total, 21 studies were
      included, 19 of which were carried out in the ED. The researchers found that the
      operative characteristics to evaluate the accuracy (calibration and
      discrimination) of the different scores were insufficiently assessed in most
      studies. Only two studies evaluated the calibration, using the Hosmer-Lemeshow
      goodness-of-fit test, and less than half of the studies evaluated the
      discrimination, using the area under the receiver operator characteristics curve.
      CONCLUSIONS: The reviewed literature did not provide enough information to assess
      the accuracy of the prognostic models in patients with suspected infection
      admitted to the ED and hospital ward. Some reports suggest a better accuracy with
      new scores like the MEDS (Mortality in Emergency Department Sepsis score), but
      the results are not consistent.

PMID- 22142676
TI  - Ruptured intracranial aneurysms and the timing of embosurgery.

PMID- 22142678
TI  - A semi-automatic algorithm for determining the demyelination load in
      metachromatic leukodystrophy.
AB  - RATIONALE AND OBJECTIVES: Metachromatic leukodystrophy is a lysosomal storage
      disorder leading to progressive demyelination of brain white matter. This is
      sensitively detected using magnetic resonance imaging. The volume of
      demyelination, the "demyelination load," could serve as a useful parameter for
      assessing both the natural course of the disease and treatment effects. The aim
      of this study was to develop and validate a semiautomated approach for
      determining the demyelination load to achieve reliable and time-efficient
      segmentation results. MATERIALS AND METHODS: The demyelination load was
      determined in 77 magnetic resonance imaging data sets from 35 patients both
      manually and semiautomatically. For manual segmentation, regarded as the gold
      standard, the software ITK-Snap was used. For semiautomatic segmentation, a new
      algorithm called Clusterize was developed and implemented in MATLAB, consisting
      of automatic iterative region growing followed by the interactive selection of
      clusters. Results were compared in terms of the obtained volumes, spatial
      overlap, and time taken to conduct the segmentation. RESULTS: Performance of the
      semiautomatic algorithm was excellent, with the volumes generated by the new
      algorithm showing good agreement with the ones generated by the gold standard
      (93.4 +/- 45.5 vs 96.1 +/- 49.0 mL, P = NS) with high spatial overlap (Dice's
      similarity coefficient = 0.7861 +/- 0.0697). The semiautomatic algorithm was
      significantly faster than the gold standard (8.2 vs 27.0 min, P < .001).
      Intrarater and interrater reliability determined high reproducibility of the
      method. CONCLUSION: The demyelination load in metachromatic leukodystrophy can be
      determined in a time-efficient manner using a semiautomatic algorithm, showing
      high agreement with the current gold standard.

PMID- 22142677
TI  - Loss of white matter microstructural integrity is associated with adverse
      neurological outcome in tuberous sclerosis complex.
AB  - RATIONALE AND OBJECTIVES: Tuberous sclerosis complex (TSC) is a genetic
      neurocutaneous syndrome in which cognitive and social-behavioral outcomes for
      patients vary widely in an unpredictable manner. The cause of adverse neurologic
      outcome remains unclear. The aim of this study was to investigate the hypothesis
      that disordered white matter and abnormal neural connectivity are associated with
      adverse neurologic outcomes. MATERIALS AND METHODS: Structural and diffusion
      magnetic resonance imaging was carried out in 40 subjects with TSC (age range,
      0.5-25 years; mean age, 7.2 years; median age, 5 years), 12 of whom had autism
      spectrum disorders (ASD), and in 29 age-matched controls. Tractography of the
      corpus callosum was used to define a three-dimensional volume of interest.
      Regional averages of four diffusion scalar parameters of the callosal projections
      were calculated for each subject. These were the average fractional anisotropy
      (AFA) and the average mean, radial, and axial diffusivity. RESULTS: Subjects with
      TSC had significantly lower AFA and higher average mean, radial, and axial
      diffusivity values compared to controls. Subjects with TSC and ASD had
      significantly lower AFA values compared to those without ASD and compared to
      controls. Subjects with TSC without ASD had similar AFA values compared to
      controls. CONCLUSION: Diffusion tensor scalar parameters provided measures of
      properties of the three-dimensional callosal projections. In TSC, changes in
      these parameters may reflect microstructural changes in myelination, axonal
      integrity, or extracellular environment. Alterations in white matter
      microstructural properties were associated with TSC, and larger changes were
      associated with TSC and ASD, thus establishing a relationship between altered
      white matter microstructural integrity and brain function.

PMID- 22142679
TI  - Prognostic value of the quantitative metabolic volumetric measurement on 18F-FDG
      PET/CT in Stage IV nonsurgical small-cell lung cancer.
AB  - RATIONALE AND OBJECTIVES: Stage IV non-small-cell lung cancer (NSCLC) consists of
      a heterogeneous group of patients with different prognoses. We assessed the
      prognostic value of baseline whole body tumor burden as measured by metabolic
      tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake values
      (SUV(max) and SUV(mean)) of all tumors in nonsurgical patients with Stage IV
      NSCLC. MATERIALS AND METHODS: Ninety-two consecutive patients with newly
      diagnosed Stage IV NSCLC who had a pretreatment F-18 fludeoxyglucose positron
      emission tomography/computed tomography scan were retrospectively reviewed. The
      MTV, TLG, SUV(mean), and SUV(max) of whole-body (WB) tumors were measured with
      the MIMvista workstation with manual adjustment. RESULTS: There was a
      statistically significant association between overall survival (OS) and
      ln(MTV)/ln(TLG) at the level of WB tumor burden (MTV(WB)) and of primary tumor
      (MTV(T)). The hazard ratio (HR) for a 1-unit increase of ln(MTV(WB)) and
      ln(MTV(T)) before and after adjusting for age and gender was 1.48/1.48 (both P <
      .001) and 1.25/1.25 (P = .006, .007), respectively. The HR for a 1-unit increase
      of ln(TLG(WB)) and ln(TLG(T)) before and after adjusting for age and gender was
      1.37/1.37 (both P = .001) and 1.19/1.19 (P = .001, .017), respectively. There was
      no statistically significant association between OS and ln(SUV(max)) and
      ln(SUV(mean)) at WB tumor burden, primary tumor, nodal metastasis, or distant
      metastasis (P > .05). There was low interobserver variability between two
      radiologists with concordance correlation coefficients of 0.90 for ln(MTV(WB))
      and greater than 0.90 for SUV(maxWB), SUV(meanWB), and ln(TLG(WB)). CONCLUSION:
      Baseline WB metabolic tumor burden, as measured with MTV and TLG, is a prognostic
      measurement in patients within Stage IV NSCLC with low interobserver variability.
      This study also suggests pretreatment MTV and TLG measurements may be used to
      further stratify patients with Stage IV NSCLC and are better prognostic measures
      than SUV(max) and SUV(mean) measurements.

PMID- 22142680
TI  - Use of BMI guidelines and individual dose tracking to minimize radiation exposure
      from low-dose helical chest CT scanning in a lung cancer screening program.
AB  - RATIONALE AND OBJECTIVES: The increasing use of computed tomography (CT) has been
      accompanied by rising concerns over potential radiation-related health risks,
      especially cancer, and a need to minimize such risks. MATERIALS AND METHODS: We
      conducted 2186 low-dose helical chest CT scans among 1235 nuclear weapons workers
      at elevated risk of lung cancer, setting the CT scanner tube current at 30 mAs
      for all participants with BMI <35 kg/m(2) and permitting technologists to raise
      mAs levels for participants with BMI >=35 kg/m(2). Dose-length product (DLP) was
      recorded from the CT scanner, permitting calculation of effective dose. Phantom
      based estimates of effective dose were also made. A chest radiologist recorded
      acceptability of image quality. RESULTS: The study population was significantly
      overweight: 79% exceeded a body mass index (BMI) >25 kg/m(2) and 37.1% exceeded a
      BMI >=30 kg/m(2). Nearly 90% of CT scans were performed using a tube current
      setting of 30 mAs and had a mean DLP-based effective dose of 1.3 mSv. The phantom
      based estimate of effective dose was lower at 1.1 mSv. Among participants with a
      BMI >=35 kg/m(2), 92% were scanned at 40 or 50 mAs, which was associated with a
      DLP-based effective dose of 1.6 and 2.0 mSv, respectively. Image quality was
      satisfactory in 99.8% of scans. CONCLUSION: Application of simple BMI-based
      guidelines and DLP tracking of low-dose helical chest CT scans in a lung cancer
      screening program minimizes radiation dose, even in a largely overweight
      population.

PMID- 22142681
TI  - Can whole-body low-dose multidetector CT exclude the presence of myeloma bone
      disease in patients with monoclonal gammopathy of undetermined significance
      (MGUS)?
AB  - RATIONALE AND OBJECTIVES: To determine the benefit of using whole-body low-dose
      computed tomography (WBLD-CT) in patients with monoclonal gammopathy of
      undetermined significance (MGUS) for exclusion of multiple myeloma (MM) bone
      disease. MATERIALS AND METHODS: Seventy-one consecutive patients with confirmed
      MGUS (as defined by the latest criteria of the International Myeloma Working
      Group) who underwent WBLD-CT for diagnosis were identified retrospectively by a
      search of our institution's electronic medical record database (2002-2009).
      Patients were classified as low-risk or intermediate/high-risk and followed over
      a >=2-year period with additional CT imaging and/or laboratory parameters.
      Presence of osteolysis, medullary, or extramedullary abnormalities compatible
      with involvement by MM was recorded. A diffuse or focal increase in medullary
      density to Hounsfield unit (HU) values >20 HU/>0 HU was considered suspicious for
      bone marrow infiltration if no other causes identifiable. RESULTS: The presence
      of osteolysis was excluded in all 71 patients with MGUS at initial diagnosis and
      patients were surveilled for >=2 years. Lytic changes were observed at follow-up
      in 1/71 patients that progressed to MM and were detectable via WBLD-CT at an
      early stage (even before a significant rise in M-protein was recorded). In 3/71
      patients with MGUS (4%) suspicious bone marrow attenuation values were measured,
      disclosing disease progression to smoldering myeloma in another patient and false
      positive results in 2/71 patients. Bone marrow attenuation assessment resulted in
      a specificity and negative predictive value of 97%, respectively. No significant
      difference with respect to bone marrow attenuation was observed in patients with
      low-risk MGUS versus intermediate- to high-risk MGUS. One of 71 patients showed
      serologic disease progression to active MM without bone abnormalities detectable.
      CONCLUSION: WBLD-CT reliably excludes findings compatible with myeloma in MGUS
      and thereby complements hematologic laboratory analysis.

PMID- 22142683
TI  - Promotion as a clinician educator in academic radiology departments: guidelines
      at three major institutions.
AB  - Faculty promotion within an academic department of radiology may place emphasis
      on scientific research, administrative contributions, educational contributions,
      or a combination of all endeavors that enrich the department and further its
      academic mission. For those departments considering the establishment of a
      promotion pathway that emphasizes teaching talents and education-oriented
      research, the authors provide examples of three different clinician-educator
      faculty appointment and promotion schemes. Faculty development and defining
      scholarly work as a clinician-educator, as well as documentation of academic
      productivity within this pathway, are discussed.

PMID- 22142682
TI  - Parametric histogram analysis of dynamic contrast-enhanced MRI in multiple
      myeloma: a technique to evaluate angiogenic response to therapy?
AB  - RATIONALE AND OBJECTIVES: From dynamic contrast-enhanced magnetic resonance
      imaging, it is known that microcirculation patterns in multiple myeloma differ
      depending on the infiltration pattern. The purpose of this study was to evaluate
      histogram analysis of dynamic contrast-enhanced magnetic resonance imaging in MM
      to monitor early treatment response on the basis of microcirculation patterns.
      MATERIALS AND METHODS: A total of 51 patients with multiple myeloma requiring
      therapy were examined. Dynamic contrast-enhanced magnetic resonance imaging of
      the lumbar spine was performed before and after conventional or high-dose
      chemotherapy with autologous stem cell transplantation. Statistical analysis
      included 245 vertebrae and dynamic microcirculation parameters as displayed in
      histograms. Resulting parameters (amplitude, exchange rate constant, skewness,
      kurtosis, and left shift) were correlated with therapeutic response. RESULTS:
      More than 70% of histograms derived from the microcirculation parameters showed a
      difference between the maximum peak before and after therapy (left shift).
      However, there was no significant difference between the particular treatment.
      Significantly different skewness of amplitude in 98% and kurtosis of exchange
      rate constant (94.1% and 98%) were seen in the patients who responded to
      treatment (P for each < .05). CONCLUSIONS: Histogram analysis revealed early
      changes after therapy resulting in a shift toward more (kurtosis) and lower
      values (skewness) of microcirculation parameters. Therefore, histogram analysis
      can determine and describe if a chosen therapy works at all. However, there were
      no differences between the chosen therapies. This needs to be reevaluated in a
      larger number of treated patients. Histogram analysis can also be an adjunct to a
      subjective visual analysis but is hampered by heterogeneous infiltration pattern
      seen in multiple myeloma.

PMID- 22142684
TI  - Cars in my life.

PMID- 22142685
TI  - Dendrimer-based multivalent methotrexates as dual acting nanoconjugates for
      cancer cell targeting.
AB  - Cancer-targeting drug delivery can be based on the rational design of a
      therapeutic platform. This approach is typically achieved by the
      functionalization of a nanoparticle with two distinct types of molecules, a
      targeting ligand specific for a cancer cell, and a cytotoxic molecule to kill the
      cell. The present study aims to evaluate the validity of an alternative
      simplified approach in the design of cancer-targeting nanotherapeutics:
      conjugating a single type of molecule with dual activities to nanoparticles,
      instead of coupling a pair of orthogonal molecules. Herein we investigate whether
      this strategy can be validated by its application to methotrexate, a dual-acting
      small molecule that shows cytotoxicity because of its potent inhibitory activity
      against dihydrofolate reductase and that binds folic acid receptor, a tumor
      biomarker frequently upregulated on the cancer cell surface. This article
      describes a series of dendrimer conjugates derived from a generation 5
      polyamidoamine (G5 PAMAM) presenting a multivalent array of methotrexate and also
      demonstrates their dual biological activities by surface plasmon resonance
      spectroscopy, a cell-free enzyme assay, and cell-based experiments with KB cancer
      cells.

PMID- 22142687
TI  - Looking beyond borders: integrating best practices in benefit-risk analysis into
      the field of food and nutrition.
AB  - An integrated benefit-risk analysis aims to give guidance in decision situations
      where benefits do not clearly prevail over risks, and explicit weighing of
      benefits and risks is thus indicated. The BEPRARIBEAN project aims to advance
      benefit-risk analysis in the area of food and nutrition by learning from other
      fields. This paper constitutes the final stage of the project, in which
      commonalities and differences in benefit-risk analysis are identified between the
      Food and Nutrition field and other fields, namely Medicines, Food Microbiology,
      Environmental Health, Economics and Marketing-Finance, and Consumer Perception.
      From this, ways forward are characterized for benefit-risk analysis in Food and
      Nutrition. Integrated benefit-risk analysis in Food and Nutrition may advance in
      the following ways: Increased engagement and communication between assessors,
      managers, and stakeholders; more pragmatic problem-oriented framing of
      assessment; accepting some risk; pre- and post-market analysis; explicit
      communication of the assessment purpose, input and output; more human (dose
      response) data and more efficient use of human data; segmenting populations based
      on physiology; explicit consideration of value judgments in assessment;
      integration of multiple benefits and risks from multiple domains; explicit
      recognition of the impact of consumer beliefs, opinions, views, perceptions, and
      attitudes on behaviour; and segmenting populations based on behaviour; the
      opportunities proposed here do not provide ultimate solutions; rather, they
      define a collection of issues to be taken account of in developing methods,
      tools, practices and policies, as well as refining the regulatory context, for
      benefit-risk analysis in Food and Nutrition and other fields. Thus, these
      opportunities will now need to be explored further and incorporated into benefit
      risk practice and policy. If accepted, incorporation of these opportunities will
      also involve a paradigm shift in Food and Nutrition benefit-risk analysis towards
      conceiving the analysis as a process of creating shared knowledge among all
      stakeholders.

PMID- 22142686
TI  - Magnoliae Cortex inhibits intimal thickening of carotid artery through modulation
      of proliferation and migration of vascular smooth muscle cells.
AB  - Endovascular injury leads to proliferation and migration of vascular smooth
      muscle cells from the media to the intima leading to the intimal thickening. The
      objective of this study was to examine the effect of Magnoliae Cortex extract
      (MOE) on intimal thickening of rat carotid artery injured by balloon endothelial
      denudation. MOE was administered orally using gastric sonde at three different
      doses MOE200 (200 mg/kg), MOE400 (400 mg/kg), and MOE800 (800 mg/kg) for 14 days
      from the day of balloon injury. Also, in vitro assays of proliferation, migration
      and expression of matrix metalloproteinase-2 (MMP-2) in human aortic smooth
      muscle cells (HASMCs) were carried out using 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, transwell boyden chamber method and
      gelatin zymography, respectively. Oral administration of MOE400 and MOE800 for 14
      days significantly inhibited intimal area, intimal/medial ratio (I/M), stenosis
      rate, expression of proliferating cell nuclear antigen (PCNA), MMP-2, and -9 in
      denudated rat carotid artery. Our in vitro assays revealed that MOE dose
      dependently inhibited proliferation, migration and expression of MMP-2 in HASMCs.
      Thus, the results suggest that MOE can be considered as a therapeutic value in
      the prevention of atherosclerosis because restenosis after percutaneous
      transluminal coronary angioplasty (PTCA) is supposed to be 'accelerated
      atherosclerosis'.

PMID- 22142688
TI  - Protective effects of total alkaloidal extract from Murraya koenigii leaves on
      experimentally induced dementia.
AB  - Dementia is a syndrome of gradual onset and continuous decline of higher
      cognitive functioning. It is a common disorder in older persons and has become
      more prevalent today. The fresh leaves of Murraya koenigii are often added to
      various dishes in Asian countries due to the delicious taste and flavor that they
      impart. These leaves have also been proven to have health benefits. In the
      present study, the effect of total alkaloidal extract from M. koenigii leaves
      (MKA) on cognitive functions and brain cholinesterase activity in mice were
      determined. In vitro beta-secretase 1 (BACE1) inhibitory activity was also
      evaluated. The total alkaloidal extract was administered orally in three doses
      (10, 20 and 30 mg/kg) for 15 days to different groups of young and aged mice.
      Elevated plus maze and passive avoidance apparatus served as the exteroceptive
      behavioral models for testing memory. Diazepam-, scopolamine-, and ageing-induced
      amnesia served as the interoceptive behavioral models. MKA (20 and 30 mg/kg,
      p.o.) showed significant improvement in memory scores of young and aged mice.
      Furthermore, the same doses of MKA reversed the amnesia induced by scopolamine
      (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Interestingly, the brain
      cholinesterase activity was also reduced significantly by total alkaloidal
      extract of M. koenigii leaves. The IC50 value of MKA against BACE1 was 1.7
      MUg/mL. In conclusion, this study indicates MKA to be a useful remedy in the
      management of Alzheimer's disease and dementia.

PMID- 22142689
TI  - Evaluation of the cytotoxicity of cigarette smoke condensate by a cellular
      impedance biosensor.
AB  - In this study, a cytotoxicity assay was developed for profiling the cytotoxicity
      of cigarette smoke condensates (CSCs) base on a cellular impedance biosensor
      (CIB). Compared with the traditional in vitro cytotoxicity assays, this CIB-based
      method offered distinct advantages in real-time kinetic measurement which
      provided a comprehensive understanding of cellular responses for the entire
      duration of the experiment and prediction of the potential mechanism of action of
      a given treatment. The time-dependent cell response profiles provided valid
      evidences for optimization of cell number per well, cell quality control, and
      identification of the optimal time points for compound treatment and endpoint
      assays. According to the time dependent IC50 values, the CIB could provide
      dynamic information that can be used to identify maximum toxicity of cigarette
      smoke and reversibility of the toxic effects which are difficult to achieve by
      the endpoint assays. The comparative IC50 values indicated that the as-developed
      biosensor offered analytical results in good consistency with the commonly used
      NRU method. The features of the CIB-based cytotoxicity assay, such as no cell
      labeling, automatic detection, and easy operation, give this assay potential to
      become routine setting for evaluating the cytotoxicity of CSCs.

PMID- 22142690
TI  - Sources of and technical approaches for the abatement of tobacco specific
      nitrosamine formation in moist smokeless tobacco products.
AB  - The presence of TSNA has been suggested as a potentially important cancer risk
      factor for moist smokeless tobacco (MST) products. We describe studies of the
      impact of tobacco agronomic and production practices which influence TSNA
      formation. TSNA were measured at points in the MST production chain from the farm
      to the finished product at the end of shelf life. Analyses were conducted to
      define points at which TSNA may occur, the factors related to the magnitude of
      occurrence, and actions which may be taken to mitigate such occurrence. Weather
      conditions during the curing season can have a dramatic impact on TSNA levels in
      tobacco, with wet seasons markedly increasing TSNA levels in cured tobacco. TSNA
      levels in MST do not increase beyond levels in cured tobacco when production
      practices limit the presence of nitrate reducing bacteria. Therefore, TSNA in
      such products are a function of the agronomic practices and conditions under
      which tobacco is produced at the farm level. Regional and annual variation in
      TSNA levels results from the stochastic nature of agronomic factors related to
      TSNA formation during tobacco growing and curing.

PMID- 22142691
TI  - Protection by [6]-shogaol against lipopolysaccharide-induced toxicity in murine
      astrocytes is related to production of brain-derived neurotrophic factor.
AB  - [6]-Shogaol has beneficial effects in spinal neuronal regeneration, but
      associated molecules and mechanisms are not identified. Neurotrophic factors,
      including brain-derived neurotrophic factor (BDNF), are associated with
      proliferation and differentiation of neuronal cells and exert a neuroprotective
      effect in neurodegenerative models. We investigated whether treatment with [6]
      shogaol increases BDNF expression in lipopolysaccharide (LPS)-treated astrocytes,
      and examined the effect of [6]-shogaol on neuronal protection. [6]-Shogaol
      significantly attenuated the cell death induced by LPS. Western blotting showed
      that [6]-shogaol treatment reduced Bax expression and increased B-cell lymphoma
      (Bcl)-2 and BclxL expression in LPS-treated cells, consistent with the effects of
      BDNF treatment. Furthermore, K252a, a blocker of neurotrophic factors, attenuated
      the cellular protective effects of [6]-shogaol and BDNF. This study provides the
      first evidence that [6]-shogaol increases the expression of BDNF in LPS-treated
      astrocytes. Furthermore, these experimental results indicate that production of
      BDNF in astrocytes might be related to altered cell viability following [6]
      shogaol treatment. Thus, the neuroprotective effects of [6]-shogaol is mediated
      by up-regulation of BDNF.

PMID- 22142692
TI  - Bisphenol A impairs insulin signaling and glucose homeostasis and decreases
      steroidogenesis in rat testis: an in vivo and in silico study.
AB  - Bisphenol A (BPA) is a potential endocrine disruptor and testicular toxicant.
      Recently, we have reported that exposure to BPA increases plasma insulin and
      glucose levels and decreases the levels of glycolytic enzymes, glucose
      transporter-8 (GLUT-8) and insulin receptor substrate-2 (IRS-2) in rat testis. In
      the present study we sought to investigate the effects of low doses of BPA on
      insulin signaling molecules, glucose transporter-2 (GLUT-2) and steroidogenesis
      in rat testis. BPA was administered to rats by oral gavage at doses of 0.005,
      0.5, 50 and 500 MUg/kg body weight/day for 45 days. A positive control was
      maintained by administering 17-beta-estradiol (50 MUg/kg body weight/day).
      Decreased levels of insulin, insulin receptor (IR), insulin receptor substrate-1
      (IRS-1), phosphoinositide 3-kinase (PI-3 kinase) and GLUT-2 were observed in rat
      testis following BPA administration. Dose-dependent decrease in the activities of
      antioxidant enzymes, 3-beta-hydroxysteroid dehydrogenase (3beta-HSD), 17-beta
      hydroxysteroid dehydrogenase (17beta-HSD), Steroidogenic Acute Regulatory Protein
      (StAR) and testosterone were also observed. Molecular docking of BPA, 17-beta
      estradiol, cytochalasin B and glucose with GLUT-2 and GLUT-8 revealed the higher
      binding affinity of BPA with GLUT-2 and GLUT-8. Thus, BPA impairs insulin
      signaling and glucose transport in rat testis which could consequently lead to
      impairment of testicular functions.

PMID- 22142694
TI  - Galangin induces apoptosis in gastric cancer cells via regulation of ubiquitin
      carboxy-terminal hydrolase isozyme L1 and glutathione S-transferase P.
AB  - Galangin has been shown to have anti-cancer property against several types of
      cancer cells. Many studies have described the anti-oxidant and apoptotic effects
      of galangin. However, the mechanism of galangin-induced apoptosis has not yet
      been studied for human gastric cancer cells. We investigated galangin-induced
      apoptosis of human gastric cancer SNU-484 cells. Galangin inhibited proliferation
      of SNU-484 cells in a dose- and time-dependent manner. The results showed that
      galangin significantly decreased the viability of SNU-484 cells at 50-200 MUM for
      24 h and 48 h. Galangin-induced cell death was characterized with the changes in
      cell morphology, DNA fragmentation, cell cycle, activation of caspase-3/-9, poly
      (ADP-ribose) polymerase (PARP) cleavage, and expression of MAP kinase such as
      ERK1/2 and JNK. For identification of proteins potentially involved in apoptosis,
      a two-dimensional electrophoresis was employed. Proteomic analysis showed that
      several proteins were associated with anti-cancer properties of galangin. Of
      particular interest, these proteins included ubiquitin carboxy-terminal hydrolase
      isozyme L1 (Uch-L1) and glutathione S-transferase P (GSTP), which are involved in
      apoptosis of SNU-484 cells. Western blot analysis confirmed up-regulation of Uch
      L1 and down-regulation of GSTP following galangin treatment. Our results suggest
      that Uch-L1 and GSTP be involved in galangin-induced apoptosis in human gastric
      cancer SNU-484 cells.

PMID- 22142695
TI  - Preparation, antioxidant and antitumor activities in vitro of different
      derivatives of levan from endophytic bacterium Paenibacillus polymyxa EJS-3.
AB  - A levan-type exopolysaccharide (EPS) from Paenibacillus polymyxa EJS-3 was
      successfully acetylated, phosphorylated and benzylated, respectively, affording
      its derivatives of acetylated levan (AL), phosphorylated levan (PL) and
      benzylated levan (BL). Then, the antioxidant and antitumor activities in vitro of
      the natural polysaccharide and its derivatives were determined. As results, AL,
      BL and PL all exhibited higher reducing power, scavenging activity against
      superoxide radical and scavenging activity on hydroxyl radical than the natural
      polysaccharide, EPS-1. In addition, AL, BL and PL also exhibited higher
      antiproliferative activity against human gastric cancer BGC-823 cells in vitro
      than EPS-1. The enhanced activities of the derivatives were probably due to the
      introduction of acetyl, benzyl, or phosphoryl groups into EPS-1 molecules that
      increased electron-donating ability and affinity with the receptors on immune
      cells. The results suggested that the derivatives could be explored as promising
      antioxidant and antitumor agents.

PMID- 22142693
TI  - Fumonisin B1 and risk of hepatocellular carcinoma in two Chinese cohorts.
AB  - Fumonisin B1 (FB1), a mycotoxin that contaminates corn in certain climates, has
      been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether
      a relationship between FB1 and HCC exists in humans is not known. To examine the
      hypothesis, we conducted case-control studies nested within two large cohorts in
      China; the Haimen City Cohort and the General Population Study of the Nutritional
      Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels
      were determined in 271 HCC cases and 280 controls. In the General Population
      Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases
      and 147 controls. In each population, odds ratios and 95% confidence intervals
      (95%CI) from logistic regression models estimated the association between
      measurable FB1 and HCC, adjusting for hepatitis B virus infection and other
      factors. A meta-analysis that included both populations was also conducted. The
      analysis revealed no statistically significant association between FB1 and HCC in
      either Haimen City (OR=1.10, 95%CI=0.64-1.89) or in Linxian (OR=1.47, 95%CI=0.70
      3.07). Similarly, the pooled meta-analysis showed no statistically significant
      association between FB1 exposure and HCC (OR=1.22, 95%CI=0.79-1.89). These
      findings, although somewhat preliminary, do not support an associated between FB1
      and HCC.

PMID- 22142696
TI  - Antioxidant phenolic profile from ethyl acetate fraction of Fructus Ligustri
      Lucidi with protection against hydrogen peroxide-induced oxidative damage in SH
      SY5Y cells.
AB  - In this study, we demonstrated the antioxidant and protective properties of crude
      extract and fractions from Fructus Ligustri Lucidi (FLL) against hydrogen
      peroxide (H2O2)-induced oxidative damage in SH-SY5Y cells. The contents of their
      phytochemical profiles were determined by spectrophotometric methods and high
      performance liquid chromatography using a photodiode array detector. FLL crude
      extract possessed appreciable scavenging capacity against 1,1-diphenyl-2
      picrylhydrazyl and H2O2. The ethyl acetate (EtOAc) fraction was the most active
      fraction in scavenging free radicals and H2O2. Following exposure of cells to
      H2O2, there was a marked decrease in cell survival and intracellular antioxidant
      enzymes, and then intracellular oxidative stress, the level of lipid
      peroxidation, and caspase-3 activity were increased. Simultaneous treatment with
      the EtOAc fraction blocked these H2O2-induced cellular events. Hydroxytyrosol and
      salidroside are major components of the EtOAc fraction. These results show that
      the phenolic-enriched EtOAc fraction of FLL contains tyrosol-related derivatives
      and exerts the protective effects against H2O2 toxicity via its free radical
      scavenging activity and ability to elevate the levels of antioxidant enzymes.

PMID- 22142697
TI  - Acute arrhythmogenesis after myocardial infarction in normotensive rats:
      influence of high salt intake.
AB  - A high salt diet is a known risk factor for cardiovascular diseases that leads to
      cardiac hypertrophy and creates a substrate for arrhythmias and sudden death.
      However, acute arrhythmogenesis after infarction has not been studied. Male
      Wistar rats (21 days) received drinking water (MI) or 1% NaCl solution (MI-Salt
      C) for 4 weeks. Water was given to another group for 4 weeks, and on the day
      before surgery, animals received a 1% NaCl solution (MI-Salt-A). Non-invasive
      systolic blood pressure (SBP) was obtained before surgery. Myocardial infarction
      (MI) was produced by permanent occlusion of the left coronary artery.
      Electrocardiogram was monitored during the first 30 min post-occlusion to
      evaluate arrhythmias. Although SBP was not altered by salt intake (SHAM: 114+/-2,
      MI: 112+/-2, MI-Salt-C: 115+/-2, MI-Salt-A: 116+/-4 mm Hg), ventricular
      hypertrophy was observed in the animals receiving chronic salt diet (SHAM: 0.22+/
      0.008, MI: 0.23+/-0.007, MI-Salt-C: 0.28+/-0.01; MI-Salt-A: 0.23+/-0.01 g/cm;
      P<0.05). Ventricular premature beats increased in both salt-loaded groups
      compared to MI group (MI: 805+/-81, MI-Salt-C: 1145+/-98; MI-Salt-A: 1023+/-77;
      P<0.05). Atrioventricular blockade was only observed in animals subjected to high
      salt intake (MI-Salt-C: 38.9%; MI-Salt-A: 42.1%). High salt intake was associated
      with increased post-infarct arrhythmias; however, this effect was unrelated to
      ventricular hypertrophy.

PMID- 22142698
TI  - Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29
      human colon adenocarcinoma cell line--a comparative study.
AB  - Colon cancer is one of the serious health problems in most developed countries
      and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy
      4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis
      inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as
      duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in
      response to HN and HA treatment. At 24 h 70 MUM of HN and 32 MUM of HA showed 50%
      reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining
      showed apoptotic features of cell death induced by HN and HA. Rhodamine 123
      staining showed significant reduction in mitochondrial membrane potential induced
      by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation.
      Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were
      significantly elevated in HN and HA treated groups. Enzymic antioxidants such as
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were
      slightly decreased in their activities compared to control (untreated HT-29
      cells). Results of Western blot analysis of apoptosis associated genes revealed
      an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in
      Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT
      29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant
      imbalance.

PMID- 22142699
TI  - An examination of prescription stimulant misuse and psychological variables among
      sorority and fraternity college populations.
AB  - OBJECTIVE: The objective of this study was to examine nonmedical stimulant use
      among fraternity/sorority members and nonmembers and whether psychological
      variables (e.g., internal restlessness, depression, anxiety, and stress) were
      related to nonmedical stimulant use. METHOD: The sample consisted of 1,033
      undergraduate students from five universities located in the northeastern,
      southeastern, northwestern, southwestern, and midwestern regions of the United
      States. RESULTS: The findings revealed that fraternity and sorority members
      reported a higher rate of nonmedical stimulant use than nonmembers. In addition,
      regression analyses revealed that higher ratings of anxiety, stress, internal
      impulsivity, and internal restlessness significantly predicted nonmedical
      stimulant use. CONCLUSION: Current findings support further examination of
      nonmedical stimulant use among other college student subpopulations (i.e.,
      athletic teams, honor societies, residence halls). In addition, there is a strong
      need to develop research-based intervention and preventive measures that target
      college populations identified as being at risk for nonmedical stimulant use.

PMID- 22142701
TI  - Erythropoietin mimetic compound AGEM400(HES) binds to the same receptor as
      erythropoietin but displays a different spectrum of activities.
AB  - EPO mimetic peptides (EMPs) have a completely different structure than
      erythropoietin (EPO) or new generation recombinant erythropoiesis stimulating
      agents (ESAs) like Darbepoietin alfa (Aranesp) and continuous erythropoiesis
      stimulating agent (CERA). This study intended to compare the effects of a novel
      compound called AGEM400(HES), consisting of a dimeric EMP conjugated to
      hydroxyethyl starch (HES), to those of recombinant EPO. AGEM400(HES) efficiently
      stimulated erythropoiesis in vitro and efficiently stimulated survival of EPO
      dependent cell line UT7/EPO. It also efficiently induced phosphorylation of
      signaling proteins in these models. However, AGEM400(HES) was shown to have weak
      or absent effects on survival of, and signaling in, three different EPO
      responsive hematopoietic cell lines. In the latter models, when added in excess
      to moderate concentrations of EPO, AGEM400(HES) inhibited the activity of EPO in
      a fashion indicating receptor binding competition between EPO and AGEM400(HES).
      It was furthermore shown, using stably transfected BA/F3 cells, that the degree
      of responsiveness of a cell to AGEM400(HES) relative to its responsiveness to
      EPO, correlated with the level of EPO receptor surface expression. The findings
      presented raise intriguing possibilities because they imply that not all side
      effects said to be associated with EPO must necessarily be elicited by
      AGEM400(HES) too.

PMID- 22142702
TI  - Glial cell line-derived neurotrophic factor influences proliferation of
      osteoblastic cells.
AB  - Little is known about the role of neurotrophic growth factors in bone metabolism.
      This study investigated the short-term effects of glial cell line-derived
      neurotrophic factor (GDNF) on calvarial-derived MC3T3-E1 osteoblasts. MC3T3-E1
      expressed GDNF as well as its canonical receptors, GFRalpha1 and RET. Addition of
      recombinant GDNF to cultures in serum-containing medium modestly inhibited cell
      growth at high concentrations; however, under serum-free culture conditions GDNF
      dose-dependently increased cell proliferation. GDNF effects on cell growth were
      inversely correlated with its effect on alkaline phosphatase (AlP) activity
      showing a significant dose-dependent inhibition of relative AlP activity with
      increasing concentrations of GDNF in serum-free culture medium. Live/dead and
      lactate dehydrogenase assays demonstrated that GDNF did not significantly affect
      cell death or survival under serum-containing and serum-free conditions. The
      effect of GDNF on cell growth was abolished in the presence of inhibitors to
      GFRalpha1 and RET indicating that GDNF stimulated calvarial osteoblasts via its
      canonical receptors. Finally, this study found that GDNF synergistically
      increased tumor necrosis factor-alpha (TNF-alpha)-stimulated MC3T3-E1 cell growth
      suggesting that GDNF interacted with TNF-alpha-induced signaling in osteoblastic
      cells. In conclusion, this study provides evidence for a direct, receptor
      mediated effect of GDNF on osteoblasts highlighting a novel role for GDNF in bone
      physiology.

PMID- 22142700
TI  - DLK1, delta-like 1 homolog (Drosophila), regulates tumor cell differentiation in
      vivo.
AB  - The stem cell-like characteristics of tumor cells are not only essential for
      tumor development and malignant progression, but also significantly contribute to
      therapy resistance. However, it remains poorly understood how cancer cell
      differentiation or stemness is regulated in vivo. We investigated the role of the
      stem cell gene DLK1, or delta-like 1 homolog (Drosophila), in the regulation of
      cancer cell differentiation in vivo using neuroblastoma (NB) xenografts as a
      model. We found that loss-of-function mutants of DLK1 significantly enhanced NB
      cell differentiation in vivo likely by increasing the basal phosphorylation of
      MEK and ERK kinases, a mechanism that has been shown to facilitate neuronal
      differentiation. We also found that DLK1(+) cells are preferentially located in
      hypoxic regions. These results clearly demonstrate that DLK1 plays an important
      role in the maintenance of undifferentiated, stem cell-like phenotypes of NB
      cells in vivo.

PMID- 22142703
TI  - A novel protein with a fibrinogen-like domain involved in the innate immune
      response of Marsupenaeus japonicus.
AB  - Fibrinogen-related proteins play important roles in innate immunity. We isolated
      a fibrinogen-related protein gene (MjFREP1) in kuruma shrimp Marsupenaeus
      japonicus. MjFREP1 encoded a protein of 270 amino acids, including a 223 amino
      acid fibrinogen-like domain. Quantitative real-time polymerase chain reaction
      analysis shows that MjFREP1 is mainly expressed in the gills and the expression
      is significantly upregulated by Vibrio anguillarum, Staphylococcus aureus, or
      white spot syndrome virus (WSSV) challenge. Recombinant MjFREP1 fibrinogen-like
      domain agglutinates Gram-positive bacteria Bacillus subtilis, Bacillus
      thuringiensis, Bacillus megaterium, and S. aureus in the presence of calcium
      ions. The fibrinogen-like domain of MjFREP1 binds peptidoglycans, LPS, bacteria,
      and the VP28 of WSSV. These results suggest that the MjFREP1 may play an
      important role in the shrimp immune response against different pathogens.

PMID- 22142704
TI  - IPNV modulation of pro and anti-inflammatory cytokine expression in Atlantic
      salmon might help the establishment of infection and persistence.
AB  - IPNV is the agent of a well-characterized acute disease that produces a systemic
      infection and high mortality in farmed fish species and persistent infection in
      surviving fish after outbreaks. Because modulation of the host expression of pro
      and anti-inflammatory cytokines can help establish persistence, in this study, we
      examined the expression of IL-1beta, IL-8, IFNalpha1 and IL-10 during acute and
      persistent IPNV infection of Atlantic salmon. Results showed that IPNV infection
      induces an increase of the IFNalpha1 and IL-10 mRNA levels in the spleen and head
      kidney (HK) of fish after acute experimental infection. Levels of the pro
      inflammatory cytokines IL-1beta and IL-8 did not rise in the spleen although an
      increase of IL-1beta, but not of IL-8, was observed in head kidney. In carrier
      asymptomatic salmon, cytokine gene expression of IFNalpha1 in the spleen and IL
      10 in head kidney were also significantly higher than expression in non-carrier
      fish. Interestingly, a decrease of IL-8 expression was also observed. IPNV
      infection of SHK-1, which is a macrophage-like cell line of salmon, also induced
      an increase of expression of the anti-inflammatory cytokine IL-10 with no effects
      on the expression of IL-1beta and IL-8. The effects are induced by an unknown
      mechanism during viral infection because poly I:C and the viral genomic dsRNA
      showed the opposite effects on cytokine expression in SHK-1 cells. In summary,
      IPNV always induces up-regulation of the anti-inflammatory cytokine IL-10 in
      Atlantic salmon. As this is accompanied by a lack of induction of the pro
      inflammatory cytokines IL-1beta and IL-8, the anti-inflammatory milieu may
      explain the high frequency, prevalence and persistence of IPNV in salmon. Effects
      might be part of the viral mechanisms of immune evasion.

PMID- 22142705
TI  - Molecular cloning of orange-spotted grouper (Epinephelus coioides) TLR21 and
      expression analysis post Cryptocaryon irritans infection.
AB  - TLR21, a non-mammalian Toll like receptor, was recently identified in chicken as
      a pattern recognition receptor of unmethyl-CpG ODN, functionally similar to that
      of mammalian TLR9. Its role in fish immune defense and whether it is involved in
      anti-parasite immunity has not yet been proven. In this study, we identified a
      cDNA sequence encoding orange-spotted grouper Toll-like receptor 21 (EcTLR21),
      the open reading frame (ORF) was 2937 bp encoding a putative polypeptide of 979
      amino acid residues. Some conserved motifs in mammalian TLR9 were also conserved
      in grouper and other fish species' TLR9 and TLR21. Tissue distribution analysis
      indicated that EcTLR21 is broadly expressed in all the tissue we tested except
      muscle. High expression levels were found in the head kidney, trunk kidney,
      spleen and heart. Post Cryptocaryon irritans infection, TLR21 and TLR9
      transcripts were induced at the local infection sites (skin and gill), while
      suppressed in systemic immune organs (spleen and head kidney), indicating that
      these two receptors may play a role in host anti-parasitic immune responses.

PMID- 22142706
TI  - Dietary supplementation of fructooligosaccharide (FOS) improves the innate immune
      response, stress resistance, digestive enzyme activities and growth performance
      of Caspian roach (Rutilus rutilus) fry.
AB  - The present study investigated the effects of prebiotic fructooligosaccharide
      (FOS) on the innate immune response, stress resistance, digestive enzyme
      activities, growth factors and survival of Caspian Roach (Rutilus rutilus) fry.
      After acclimation, fish (0.67 +/- 0.03 g) were allocated into 12 tanks (50 fish
      per tank) and triplicate groups were fed a control diet or diets containing 1%,
      2% or 3% FOS. At the end of the trial (7 weeks), humoral innate immune parameters
      (serum Ig levels, lysozyme activity and alternative complement activity (ACH50)),
      resistance to salinity stress (150 g L(-1)), digestive enzyme activities
      (amylase, lipase and protease) and growth factors (final weight, weight gain,
      specific growth rate (SGR), food conversion ratio (FCR), and condition factor)
      were assessed. At the end of the study the innate immune responses (Ig levels,
      lysozyme activity and ACH50) were significantly higher in 2% and 3% FOS fed fish
      (P < 0.05), whereas, 1% dietary FOS only elevated serum lysozyme activity. All
      dietary FOS levels significantly increased resistance to a salinity stress
      challenge (P < 0.05) and highest survival was observed in the 3% FOS group.
      Similarly, digestive enzyme activities were significantly elevated with
      increasing levels of dietary FOS (P < 0.05). Subsequently, elevated growth
      performance (final weight, SGR and FCR) was observed in roach fed 2% and 3% FOS
      compared to the control group (P < 0.05). These results indicate that FOS can be
      considered as a beneficial dietary supplement for improving the immune response,
      stress resistance, digestive enzyme activities and growth performance of Caspian
      roach fry.

PMID- 22142707
TI  - Consistency between physical medicine and rehabilitation specialists and a
      radiologist in interpretation of lumbosacral radiographs.
AB  - OBJECTIVE: To investigate intra- and inter-observer reliability among physical
      medicine and rehabilitation specialists and a radiologist in interpretation of
      plain lumbar spine X-ray films in patients with low back pain. METHODS: Three
      assessors (A: a resident of PM&R, B: an experienced PM&R specialist, C: an
      experienced radiologist) read the standard lumbosacral plain radiographs of 79
      patients with 2-3 month time interval. Each assessor recorded the presence or
      absence of abnormalities on the radiograph according to a standardized assessment
      form. RESULTS: For assessors B and C, all kappa values were > 0.40. Transitional
      vertebrae abnormalities reached to the highest agreement ratio. The intrarater
      agreement showed higher kappas than the interrater agreement. The radiologists
      had the highest intrarater agreement, closely followed by the experienced PM&R
      specialist. Agreement among three assessors was substantial in sacralisation,
      lumbarisation and facet joint pathologies. CONCLUSION: We usually obtained a good
      intrarater agreement, especially for the experienced PM&R specialist and the
      radiologist indicating that experience increases diagnostic consistency. Besides
      the systematic differences in radiographic interpretation between the assessors,
      institutional specific conditions (esp. patient profile and regularities) may
      cause the phycians to pay more attention to a specific group of pathologies.

PMID- 22142708
TI  - Three-dimensional kinematics of the lower limbs in hip osteoarthritis during
      walking.
AB  - OBJECTIVE: To describe the kinematic adaptations of all lower limb joints in hip
      osteoarthritis patients during walking. METHODS: Patients with unilateral primary
      hip OA, without associated joint disorders were included. Normal subjects were
      included as controls. Gait analysis, using a 3-dimensional computerised gait
      analysis system was used to evaluate the usual spatiotemporal parameters, the
      peak motion of the hips, knees, and ankles during walking, and the intersegmental
      coordination of the lower limbs. RESULTS: Eleven patients, mean age =60.5 +/- 7
      years and nine controls, mean age=60.3 +/- 7 years, were included. The gait of
      hip OA patients was characterised as follows: a reduced stride length, a reduced
      maximal flexion and extension in the OA hip, a reduced maximal contralateral hip
      range of motion, an increased ipsi- and contralateral ankle dorsal flexion, a
      decreased ipsilateral relative temporal phase between the thighs and shanks
      segments and an increased ipsilateral relative phase between the shanks and foot
      segments. CONCLUSION: The present results suggest that hip OA patients use
      shorter stride length, less contra lateral and especially ipsilateral hip motion,
      modify ankles motion, and have a different intra-limb coordination pattern
      compared to control subjects.

PMID- 22142709
TI  - Electromyographic activity of trunk muscles during exercises with flexible and
      non-flexible poles.
AB  - OBJECTIVE: Hand-held flexible poles which are brought into oscillation to cause
      alternating forces on trunk, are advocated as training devices that are supposed
      to solicit increased levels of stabilizing trunk muscle activity. The aim of this
      study was to verify this claim by comparing electromyographic (EMG) activity of
      trunk muscles during exercises performed with a flexible pole and a rigid pole.
      METHODS: Twelve healthy females performed three different exercises with flexible
      and rigid poles. EMG activity of iliocostalis lumborum (IL), multifidus (MU),
      rectus abdominis (RA), external oblique (EO) and internal oblique (IO), and was
      continuously measured. The EMG signals were analyzed in time domain by
      calculation of the Root Mean Square (RMS) amplitudes over 250 ms windows. The
      mean RMS-values over time were normalized by the maximum RMS obtained for each
      muscle. RESULTS: The IO showed a 72% greater EMG activity during the exercises
      performed with the flexible pole than with the rigid pole (p=0.035). In exercises
      performed in standing, the IO was significantly more active than when sitting
      (p=0.006). CONCLUSION: As intended, the cyclic forces induced by the oscillating
      pole did increase trunk muscle activation. However, the effect was limited and
      significant for the IO muscle only.

PMID- 22142710
TI  - Electromyographic activity of the quadriceps components during the final degrees
      of knee extension.
AB  - An imbalance in the recruitment patterns of the quadriceps muscle has been
      implicated in patellofemoral knee pain; however ambiguity remains in the normal
      recruitment patterns of this muscle. We investigated the activity of the
      quadriceps muscle during the final degrees of knee extension, specifically in the
      medial and lateral components. Sixteen healthy subjects (age; 22.5 (+/- 3.4)
      years, body mass; 67.5 (+/- 12.1) kg and height; 173.9 (+/- 10.4) cm)
      participated.Torque and electromyographic (EMG) activity of the quadriceps muscle
      were measured during isokinetic and isometric knee extensions. Torque and EMG
      activity reduced in all component muscles during the final degrees of isokinetic
      extension, but this did not occur during isometric contractions at similar
      angles. Normalised activity of rectus femoris (RF) was greater than that of
      vastus lateralis (VL) and vastus medialis obliquus (VMO) during the final degrees
      of isokinetic knee extension at 30 degrees /sec; there were no differences
      between any component muscles at the higher velocities. VMO:VL and vastus
      medialis longus (VML):VL ratios were unchanged during knee extensions, except
      that VML:VL ratio increased significantly during the final degrees of extension
      at 30 degrees /sec. Future work should compare these results with people with
      anterior knee pain, and explore this further during activities of daily living.

PMID- 22142711
TI  - Effect of foot orthoses and short-foot exercise on the cross-sectional area of
      the abductor hallucis muscle in subjects with pes planus: a randomized controlled
      trial.
AB  - OBJECTIVE: To prevent overuse injuries related to excessively pronated feet, the
      strengthening of the foot intrinsic muscles has been recommended. The purpose of
      this study was to examine the effects of foot orthoses and a short-foot exercise
      intervention on the cross-sectional area (CSA) of the abductor hallucis (AbdH)
      muscle and strength of the flexor hallucis (FH) in subjects with pes planus.
      METHODS: Twenty-eight subjects with pes planus were randomly assigned to the foot
      orthosis (FO) group or the combined foot orthosis and short-foot exercise (FOSF)
      group for an 8-week intervention. The CSA of the AbdH muscle and the strength of
      FH were assessed before and after intervention. Data were analyzed using a mixed
      model ANOVA. RESULTS: Significant group by intervention interaction effects were
      observed in CSA of the AbdH (p=0.009) and strength of the FH (p=0.015). The
      results of the post hoc paired t-test showed that that the CSA of the AbdH muscle
      and the strength of the FH significantly increased after the intervention in both
      groups (p=0.000). The mean CSA of the AbdH muscle and the strength of FH were
      significantly greater in subjects in the FOSF group compared with subjects in the
      FO group (mean difference of FO vs. FOSF=13.61 mm(2) in CSA of AbdH muscle; 0.90
      kgf in strength of FH; p=0.008). CONCLUSIONS: Results from this study demonstrate
      that foot orthoses combined with short-foot exercise is more effective in
      increasing the CSA of the AbdH muscle and the strength of FH compared with foot
      orthoses alone. Therefore, foot orthoses combined with short-foot exercise are
      recommended for improving strength of AbdH muscle in subjects with pes planus.

PMID- 22142712
TI  - Novel augmented ADIM training using ultrasound imaging and electromyography in
      adults with core instability.
AB  - OBJECTIVE: To determine the effect of novel augmented abdominal drawing-in
      maneuver (ADIM) training using rehabilitative ultrasound imaging (RUSI) and
      electromyography (EMG) in adults with core instability. METHODS: A convenience
      sample of 20 young adults with core instability (female =4; mean age +/- standard
      deviation=24.4 +/- 2.9 years) was recruited. Core instability was determined by
      the formal test. All subjects underwent an intensive ADIM that was augmented by
      comprehensive visual feedback via a pressure biofeedback unit, RUSI, and EMG. The
      intervention was provided for 20 minutes a day, 7 days a week, over a two-week
      period. RESULTS: The paired t-test showed that both transverse abdominal (TrA)
      and internal oblique (IO) muscle thickness during ADIM were significantly greater
      than at rest (p= 0.000). However, external oblique (EO) muscle thickness remained
      relatively unchanged. The mean EMG amplitudes of the EO and erector spinae (ES)
      muscles were significantly decreased after the intervention (p=0.001, p=0.008).
      The intra-class correlation coefficient (ICC(1,2)) showed the excellent test
      retest reliability for muscle thickness (ranging from 0.90 to 0.98 in the prone
      position). CONCLUSION: This is the first evidence to demonstrate that the novel
      augmented ADIM training can effectively improve the lumbo-pelvic stabilization in
      adults with core instability.

PMID- 22142713
TI  - The effect of lumbar extension training with and without pelvic stabilization on
      lumbar strength and low back pain.
AB  - INTRODUCTION: A dynamometer employing a stabilization procedure (lumbar extension
      machine, MedX, Ocala, FL) is effective in improving strength and reducing
      symptoms of low back pain (LBP), and researchers have hypothesized that this
      effectiveness is due to the pelvic stabilization. However, effects of the
      dynamometer with and without pelvic stabilization on LBP have not been compared:
      This was the aim of the present study. METHODS: Forty-two chronic LBP patients
      were randomly assigned to a lumbar extension training with pelvic stabilization
      group (STAB; n=15), a lumbar extension without pelvic stabilization group (NO
      STAB; n=15) and a control group (n=12). STAB and NO-STAB participants completed
      one weekly session of dynamic variable resistance exercise (one set of 8-12
      repetitions to fatigue) on the lumbar extension machine (with or without pelvic
      stabilization) for 12 weeks. Pre- and post-test measures of self-reported LBP
      (101-point visual analog scale; pre-test mean of 25), related disability
      (Oswestry disability index; pre-test mean of 34) and lumbar strength were taken.
      RESULTS: After the exercise program, the STAB group increased significantly in
      lumbar strength at all joint angles, and decreased significantly in visual
      analogue and Oswestry scores. However, there were no significant changes in these
      variables in the NO-STAB and control groups. DISCUSSION: Isolated lumbar
      extension exercise is very effective in reducing LBP in chronic patients.
      However, when the pelvis is not stabilized, otherwise identical exercises appear
      ineffective in reducing LBP.

PMID- 22142714
TI  - The relationship between latent trigger point and muscle strength in healthy
      subjects: a double-blind study.
AB  - BACKGROUND: Trigger points on the palpable taut bands of the muscles are promoted
      as an important cause of musculoskeletal pain. Our hypothesis was latent trigger
      points (LTrPs) could decrease muscle strength also in healthy people. OBJECTIVES:
      The aim of our study was to investigate the relationship between LTrPs and muscle
      strength in a group of healthy adults. METHODS: In total fifty healthy adults (20
      women and 30 men) were included in the study. Trigger point examination for upper
      and middle trapezius, supraspinatus, serratus anterior and rhomboid major and
      minor were done bilaterally according to four criteria. Subjects who have at
      least two trigger points in dominant side were assigned to Group 1 (28 subjects),
      subjects who don't have any trigger points were assigned to Group 2 (23
      subjects). Muscle strength for flexion and scaption was assessed with a Hand-Held
      Dynamometer (HHD) as break test on both sides. Both the subjects and the
      examiners were blind. For statistical analysis, independent sample t test was
      used to compare the differences between two groups. RESULTS: No significant
      differences were found in muscle strength between dominant and non-dominant sides
      in both groups (p >0.05). Significant difference was observed in both sides when
      comparison of muscle strength between Group 1 and 2, muscle strength was lower in
      subjects who had trigger points (p < 0.05). CONCLUSIONS: This study indicated
      that although there is not significant difference between dominant and non
      dominant side, muscle strength is lower significantly in both %side sides in
      subjects who have trigger points in comparison with healthy subjects. Our results
      underline the importance of palpation of LTrPs in scapular and shoulder muscles
      in healthy subjects as they may contribute to the muscle strength. Further
      research is needed to facilitate a better understanding of the mechanism of LTrPs
      and to test the relationship with muscle strength.

PMID- 22142715
TI  - Osteopoikilosis associated with fibromyalgia and active myofascial trigger point
      in upper trapezius muscles.
AB  - Osteopoikilosis is a sclerosing bone dysplasia, characterized by multiple oval
      spots of radiodensities within the trabecular bone. It occurs equally common
      among men and women. Prevalence is estimated to be as high as 1:50,000. Most
      reported cases have been found incidentally on roentgenograms taken for other
      purposes. We present a 58-year-old woman with OPK associated with fibromyalgia
      and active myofascial trigger point in upper trapezius muscles.

PMID- 22142718
TI  - Global asymptotic stability of density dependent integral population projection
      models.
AB  - Many stage-structured density dependent populations with a continuum of stages
      can be naturally modeled using nonlinear integral projection models. In this
      paper, we study a trichotomy of global stability result for a class of density
      dependent systems which include a Platte thistle model. Specifically, we identify
      those systems parameters for which zero is globally asymptotically stable,
      parameters for which there is a positive asymptotically stable equilibrium, and
      parameters for which there is no asymptotically stable equilibrium.

PMID- 22142719
TI  - Role of nutritional status in predicting the length of stay in cancer: a
      systematic review of the epidemiological literature.
AB  - BACKGROUND: Length of stay (LOS) has been used as a surrogate marker for
      patients' well-being during hospital treatment. We systematically reviewed all
      pertinent literature on the role of nutritional status in predicting LOS in
      cancer. METHODS: A systematic search of human studies published in English was
      conducted using the MEDLINE data base (all articles published as of December
      2010). We searched using the terms 'nutritional status' and 'nutritional
      assessment' and 'nutritional screening' and 'malnutrition' in combination with
      the following terms: length of stay, length of hospital stay, duration of stay,
      and duration of hospitalization together with 'cancer' or 'oncology'. RESULTS:
      The MEDLINE search identified a total of 149 articles, of which only 21 met the
      selection criteria. Of the 21 studies, 10 studies investigated gastrointestinal
      cancer patients, 4 gynecological cancer, and 7 heterogeneous cancer. Eight
      studies used subjective global assessment (SGA) or patient-generated SGA (PG
      SGA), 9 used serum albumin and/or BMI, and 4 used other methods of nutritional
      assessment. CONCLUSIONS: Validated nutritional tools such as SGA/PG-SGA are
      better predictors of LOS in gastrointestinal cancers requiring surgery than in
      nonsurgical gastrointestinal cancer patients. Correcting malnutrition may
      decrease the LOS and perhaps even lower the rate of hospital readmissions in this
      population.

PMID- 22142720
TI  - Arthroscopic treatment of hip chondral defects: autologous chondrocyte
      transplantation versus simple debridement--a pilot study.
AB  - PURPOSE: To compare the effectiveness of simple arthroscopic debridement versus
      arthroscopic autologous chondrocyte transplantation (ACT) for the treatment of
      hip chondral lesions. METHODS: We carried out a controlled retrospective study of
      30 patients affected by a post-traumatic hip chondropathy of the third or fourth
      degree, according to the Outerbridge classification, measuring 2 cm2 in area or
      more. Of these patients, 15 underwent arthroscopic ACT, whereas the other 15
      underwent arthroscopic debridement. The 2 groups were similar in age, sex,
      degree, and location of the pathology. All the patients were assessed before and
      after the procedure with the Harris Hip Score (HHS). RESULTS: In both groups the
      mean follow-up was approximately 74 months (range, 72 to 76 months). The mean
      size of the defect was 2.6 cm2. The patients who underwent ACT (group A) improved
      after the procedure compared with the group that underwent debridement alone
      (group B). The mean HHS preoperatively was 48.3 (95% confidence interval [CI],
      45.4 to 51.2) in group A and 46 (95% CI, 42.7 to 49.3) in group B (P = .428 [no
      significant difference]). The final HHS was 87.4 (95% CI, 84.3 to 90.5) in group
      A and 56.3 (95% CI, 54.4 to 58.7) in group B (P < .001 [significant difference]).
      CONCLUSIONS: This study indicates that an ACT procedure can be used in the hip
      for acetabular chondral defects. LEVEL OF EVIDENCE: Level III, retrospective
      comparative study.

PMID- 22142721
TI  - Environmental risk assessment of alkylphenols from offshore produced water on
      fish reproduction.
AB  - Concern has been raised over whether environmental release of alkylphenols (AP)
      in produced water (PW) discharges from the offshore oil industry could impose a
      risk to the reproduction of fish stocks in the North Sea. An environmental risk
      assessment (ERA) was performed to determine if environmental exposure to PW APs
      in North Sea fish populations is likely to be high enough to give effects on
      reproduction endpoints. The DREAM (Dose related Risk and Effect Assessment Model)
      software was used in the study and the inputs to the ERA model included PW
      discharge data, fate information of PW plumes, fish distribution information, as
      well as uptake and elimination information of PW APs. Toxicodynamic data from
      effect studies with Atlantic cod (Gadus morhua) exposed to APs were used to
      establish a conservative environmental risk threshold value for AP concentration
      in seawater. By using the DREAM software to 1) identify the areas of highest
      potential risk and 2) integrate fish movement and uptake/elimination rates of APs
      for the chosen areas we found that the environmental exposure of fish to APs from
      PW is most likely too low to affect reproduction in wild populations of fish in
      the North Sea. The implications related to risk management of offshore PW and
      uncertainties in the risk assessment performed are discussed.

PMID- 22142722
TI  - Cloning of novel cellulases from cellulolytic fungi: heterologous expression of a
      family 5 glycoside hydrolase from Trametes versicolor in Pichia pastoris.
AB  - Total cDNA isolated from cellulolytic fungi cultured in cellulose was examined
      for the presence of sequences encoding for endoglucanases. Novel sequences
      encoding for glycoside hydrolases (GHs) were identified in Fusarium oxysporum,
      Ganoderma applanatum and Trametes versicolor. The cDNA encoding for partial
      sequences of GH family 61 cellulases from F. oxysporum and G. applanatum shares
      58 and 68% identity with endoglucanases from Glomerella graminicola and Laccaria
      bicolor, respectively. A new GH family 5 endoglucanase from T. versicolor was
      also identified. The cDNA encoding for the mature protein was completely
      sequenced. This enzyme shares 96% identity with Trametes hirsuta endoglucanase
      and 22% with Trichoderma reesei endoglucanase II (EGII). The enzyme, named TvEG,
      has N-terminal family 1 carbohydrate binding module (CBM1). The full length cDNA
      was cloned into the pPICZalphaB vector and expressed as an active, extracellular
      enzyme in the methylotrophic yeast Pichia pastoris. Preliminary studies suggest
      that T. versicolor could be useful for lignocellulose degradation.

PMID- 22142723
TI  - The laccase-catalyzed modification of lignin for enzymatic hydrolysis.
AB  - The efficient use of cellulases in the hydrolysis of pretreated lignocellulosic
      biomass is limited due to the presence of lignin. Lignin is known to bind
      hydrolytic enzymes nonspecifically, thereby reducing their action on carbohydrate
      substrates. The composition and location of residual lignin therefore seem to be
      important for optimizing the enzymatic hydrolysis of lignocellulosic substrates.
      The use of lignin-modifying enzymes such as laccase may have potential in the
      modification or partial removal of lignin from the biomass. In this study, the
      effect of lignin modification by laccase on the hydrolysis of pretreated spruce
      (Picea abies) and giant reed (Arundo donax) was evaluated. The substrates were
      first treated with laccase and then hydrolyzed with commercial cellulases.
      Laccase modification improved the hydrolysis yield of spruce by 12%, but
      surprisingly had an adverse effect on giant reed, reducing the hydrolysis yield
      by 17%. The binding properties of cellulases on the untreated and laccase-treated
      lignins were further studied using isolated lignins. The laccase treatment
      reduced the binding of enzymes on modified spruce lignin, whereas with giant
      reed, the amount of bound proteins increased after laccase treatment. Further
      understanding of the reactions of laccase on lignin will help to control the
      unspecific-binding of cellulases on lignocellulosic substrates.

PMID- 22142724
TI  - Genomic organization and genomic structural rearrangements of Sphingobium
      japonicum UT26, an archetypal gamma-hexachlorocyclohexane-degrading bacterium.
AB  - The complete genome sequencing of a gamma-hexachlorocyclohexane-degrading strain,
      Sphingobium japonicum UT26, revealed that the genome consists of two circular
      chromosomes [with sizes of 3.5 Mb (Chr1) and 682kb (Chr2)], a 191-kb large
      plasmid (pCHQ1), and two small plasmids with sizes of 32 and 5kb. The lin genes
      are dispersed on Chr1, Chr2, and pCHQ1. Comparison of the UT26 genome with those
      of other sphingomonad strains demonstrated that the "specific"lin genes for
      conversion of gamma-HCH to beta-ketoadipate (linA, linB, linC, linRED, and linF)
      are located on the DNA regions unique to the UT26 genome, suggesting the
      acquisition of these lin genes by horizontal transfer events. On the other hand,
      linGHIJ and linKLMN are located on the regions conserved in the genomes of
      sphingomonads, suggesting that the linGHIJ-encoded beta-ketoadipate pathway and
      the LinKLMN-type ABC transporter system are involved in core functions of
      sphingomonads. Based on these results, we propose a hypothesis that UT26 was
      created by recruiting the specific lin genes into a strain having core functions
      of sphingomonads. Most of the specific lin genes in UT26 are associated with
      IS6100. Our analysis of spontaneous linA-, linC-, and linRED-deletion mutants of
      UT26 revealed the involvement of IS6100 in their deduced genome rearrangements.
      These facts strongly suggest that IS6100 plays important roles both in the
      dissemination of the specific lin genes and in the genome rearrangements.

PMID- 22142725
TI  - Antioxidant compounds improved PCB-degradation by Burkholderia xenovorans strain
      LB400.
AB  - Polychlorobiphenyls (PCBs) are toxic and persistent organic pollutants that are
      widely distributed in the environment. Burkholderia xenovorans LB400 is capable
      of degrading aerobically an unusually wide range of PCBs. However, during PCB
      degradation B. xenovorans LB400 generates reactive oxygen species (ROS) that
      affect its viability. The aim of this study was to increase the efficiency of PCB
      degradation of B. xenovorans LB400 by adding antioxidant compounds that could
      increase tolerance to oxidative stress. The effect of antioxidant compounds on
      the growth, morphology and PCB-degradation by B. xenovorans LB400 was evaluated.
      alpha-Tocopherol or vitamin E (vitE) and berry extract (BE) increased slightly
      the growth of strain LB400 on biphenyl, whereas in presence of ascorbic acid or
      vitamin C (vitC) an inhibition of growth was observed. The growth of B.
      xenovorans LB400 in glucose was inhibited by the addition of 4-chlorobiphenyl (4
      CB). Interestingly, in presence of alpha-tocopherol the growth of strain LB400
      was less affected by 4-CB. By transmission electronic microscopy it was observed
      that alpha-tocopherol preserved the cell membranes and improved cell integrity of
      glucose-grown LB400 cells exposed to 4-CB, suggesting a protective effect of
      alpha-tocopherol. Notably, alpha-tocopherol increased biphenyl and 4-CB
      degradation by B. xenovorans LB400 in an aqueous solution. The effect of
      antioxidants compounds on PCB-bioremediation was evaluated in agricultural soil
      spiked with 2-chlorobiphenyl (2-CB), 4-CB and 2,4'-chlorobiphenyl (2,4'-CB). For
      bioaugmentation, LB400 cells grown on biphenyl and subsequently incubated with
      pyruvate were added to the soil. Native soil microbiota was able to remove PCBs.
      Bioaugmentation with strain LB400 increased strongly the PCB-degradation rate.
      Bioaugmentation with strain LB400 and biostimulation with alpha-tocopherol or
      berry extract increased further the PCB degradation. Half-life of 2,4'-CB
      decreased by bioaugmentation from 24 days to 4 days and by bioaugmentation in
      presence of alpha-tocopherol and berry extract to 2 days. By bioaugmentation with
      strain LB400, 85% of 2,4'-CB was degraded in 20 days, whereas bioaugmentation
      with strain LB400 and biostimulation with alpha-tocopherol or berry extract
      reduced the time to less than 13 days. This indicates that antioxidant compounds
      stimulated PCB-degradation in soil. Therefore, the addition of antioxidant
      compounds constitutes an attractive strategy for the scale-up of aerobic PCB
      bioremediation processes.

PMID- 22142726
TI  - Laccase chloride inhibition reduction by an anthraquinonic substrate.
AB  - Due to their low substrate specificity, fungal laccases have a great potential in
      industrial applications, including the bioremediation of colored wastewaters from
      textile industry. However, the presence of halides in these effluents (up to 1M
      NaCl) which inhibit laccases is a drawback for bioremediation processes. In order
      to develop an efficient enzymatic remediation process for textile dye effluent,
      the possibility to reduce this halide inhibition is conditioned by a better
      understanding of the phenomenon. The present study gives a detailed account of
      the kinetics of chloride inhibition of both ABTS (a model substrate) and ABu62
      (an anthraquinonic acid dye) oxidations catalyzed by Trametes versicolor laccase
      (LacIIIb). Chloride inhibition can be described by a mixed model for ABTS and a
      non-competitive model for ABu62 and both inhibitions are linear suggesting a
      single inhibitory site for chloride. Experiments were also conducted in presence
      of both substrates. An apparent activation of laccase was observed in the
      presence of ABu62 leading to an enhancement of the oxidation rate of ABTS. The
      extent of activation increased in the presence of chloride anions. Finally, for
      the first time to our knowledge, we evidenced that inhibition of ABTS oxidation
      by chloride can be reduced in the presence of ABu62.

PMID- 22142727
TI  - Isolation and characterization of Streptomyces, Actinoplanes, and Methylibium
      strains that are involved in degradation of natural rubber and synthetic poly(cis
      1,4-isoprene).
AB  - Rubber-degrading bacteria were screened for the production of clearing zones
      around their colonies on latex overlay agar plates. Novel three bacteria,
      Streptomyces sp. strain LCIC4, Actinoplanes sp. strain OR16, and Methylibium sp.
      strain NS21, were isolated. To the best of our knowledge, this is the first
      report on the isolation of a Gram-negative rubber-degrading bacterium other than
      gamma-proteobacteria. Gel permeation chromatography analysis revealed that these
      strains degraded poly(cis-1,4-isoprene) to low-molecular-weight products. The
      occurrence of aldehyde groups in the degradation products by NS21 was suggested
      by staining with Schiff's reagent and 1H-nuclear magnetic resonance spectroscopy.
      The lcp gene of LCIC4, which showed 99% amino acid sequence identity with that of
      Streptomyces sp. strain K30, was cloned, and contained a putative twin-arginine
      motif at its N terminus. It is located next to oxiB, which is estimated to be
      responsible for oxidation of degradation intermediate of rubber in K30. Southern
      hybridization analysis using LCIC4 lcp probe revealed the presence of a lcp
      homolog in OR16. These results suggest that the lcp-homologs are involved in
      rubber degradation in LCIC4 and OR16.

PMID- 22142728
TI  - Characterization of the 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE)
      degradation system in Janibacter sp. TYM3221.
AB  - Bacterial degradation of 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE) has
      been previously reported, however, its degradation enzyme system has not been
      characterized. In this study, a DDE-degrading bacterium, Janibacter sp. TYM3221,
      was isolated and characterized. Transformation of DDE was demonstrated by TYM3211
      resting cells grown in LB in the presence and absence of biphenyl. Gas
      chromatography-mass spectrometry analysis revealed five metabolites of DDE
      containing a meta-ring cleavage product and 4-chlorobenzoic acid, suggesting that
      TYM3221 degrades DDE to 4-chlorobenzoic acid via a meta-ring cleavage product. A
      gene cluster, bphAaAbAcAd, which codes for biphenyl dioxygenase subunits, was
      cloned from TYM3221. A mutant strain with a bphAa-gene inactivation did not grow
      on biphenyl, and showed no DDE degradation activity. These results indicate that
      in strain TYM3221, the bphAa-coded biphenyl dioxygenase is involved not only in
      the metabolism of biphenyl but also in the degradation of DDE.

PMID- 22142729
TI  - Engineered tobacco and microalgae secreting the fungal laccase POXA1b reduce
      phenol content in olive oil mill wastewater.
AB  - Olive oil mill wastewaters (OMWs) are characterised by low pH and a high content
      of mono- and polyaromatic compounds that exert microbial and phytotoxic activity.
      The laccase cDNA of the poxA1b gene from Pleurotus ostreatus, carrying a signal
      peptide sequence for enzyme secretion and driven by the CaMV 35S promoter, was
      cloned into a plant expression vector. Nuclear genetic transformation was carried
      out by co-cultivation of Agrobacterium tumefaciens with tobacco cv Samsun NN
      leaves and cells of five different microalgae accessions belonging to the genera
      Chlamydomonas, Chlorella and Ankistrodesmus. Transgenic plants and microalgae
      were able to express and secrete the recombinant laccase in the root exudates and
      the culture medium, respectively. In comparison to untransformed controls, the
      ability to reduce phenol content in OMW solution was enhanced up to 2.8-fold in
      transgenic tobacco lines and by up to about 40% in two microalgae accessions. The
      present work provides new evidence for metabolic improvement of green organisms
      through the transgenic approach to remediation.

PMID- 22142730
TI  - Covalent immobilization of catalase onto spacer-arm attached modified florisil:
      characterization and application to batch and plug-flow type reactor systems.
AB  - Catalase was covalently immobilized onto florisil via glutaraldehyde (GA) and
      glutaraldehyde+6-amino hexanoic acid (6-AHA) (as a spacer arm). Immobilizations
      of catalase onto modified supports were optimized to improve the efficiency of
      the overall immobilization procedures. The V(max) values of catalase immobilized
      via glutaraldehyde (CIG) and catalase immobilized via glutaraldehyde+6-amino
      hexanoic acid (CIG-6-AHA) were about 0.6 and 3.4% of free catalase, respectively.
      The usage of 6-AHA as a spacer arm caused about 40 folds increase in catalytic
      efficiency of CIG-6-AHA (8.3 * 105 M-1 s-1) as compared to that of CIG (2.1 * 104
      M-1 s-1). CIG and CIG-6-AHA retained 67 and 35% of their initial activities at 5 
      degrees C and 71 and 18% of their initial activities, respectively at room
      temperature at the end of 6 days. Operational stabilities of CIG and CIG-6-AHA
      were investigated in batch and plug-flow type reactors. The highest total amount
      of decomposed hydrogen peroxide (TAD-H2O2) was determined as 219.5 MUmol for CIG
      6-AHA in plug-flow type reactor.

PMID- 22142731
TI  - Preparative-scale kinetic resolution of racemic styrene oxide by immobilized
      epoxide hydrolase.
AB  - Epoxide hydrolase from Aspergillus niger was immobilized onto the modified
      Eupergit C 250 L through a Schiff base formation. Eupergit C 250 L was treated
      with ethylenediamine to introduce primary amine groups which were subsequently
      activated with glutaraldehyde. The amount of introduced primary amine groups was
      220 MUmol/g of the support after ethylenediamine treatment, and 90% of these
      groups were activated with glutaraldehyde. Maximum immobilization of 80% was
      obtained with modified Eupergit C 250 L under the optimized conditions. The
      optimum pH was 7.0 for the free epoxide hydrolase and 6.5 for the immobilized
      epoxide hydrolase. The optimum temperature for both free and immobilized epoxide
      hydrolase was 40  degrees C. The free epoxide hydrolase retained 52 and 33% of
      its maximum activity at 40 and 60  degrees C, respectively after 24h
      preincubation time whereas the retained activities of immobilized epoxide
      hydrolase at the same conditions were 90 and 75%, respectively. Immobilized
      epoxide hydrolase showed about 2.5-fold higher enantioselectivity than that of
      free epoxide hydrolase. A preparative-scale (120 g/L) kinetic resolution of
      racemic styrene oxide using immobilized preparation was performed in a batch
      reactor and (S)-styrene oxide and (R)-1-phenyl-1,2-ethanediol were both obtained
      with about 50% yield and 99% enantiomeric excess. The immobilized epoxide
      hydrolase was retained 90% of its initial activity after 5 reuses.

PMID- 22142732
TI  - Overexpression of a bacterial chymotrypsin: application for L-amino acid ester
      hydrolysis.
AB  - In this work, a reliable protocol was designed to rapidly express and purify a
      microbial chymotrypsin(ogen) as a useful alternative to using animal proteases.
      The cDNA encoding for chymotrypsinogen from the deuteromycete Metarhizium
      anisopliae (chy1) was overexpressed in an Origami2(DE3) E. coli strain deficient
      in thioredoxin reductase and glutathione reductase activities, thus possibly
      allowing disulfide exchange. By using a quick purification protocol, in which the
      hexahistidine tag was added at the C-terminal end of the protease, the
      recombinant CHY1 protein could be purified in a single step on an Ni-NTA column
      as a mixture of 19.5- and 15-kDa mature active forms and did not require further
      activation/maturation steps. This expression and purification procedure offers an
      easier and faster means of producing recombinant CHY1 chymotrypsin than that
      previously described for Pichia pastoris. The kinetic properties could be
      characterized and CHY1 chymotrypsin was demonstrated to efficiently catalyze N
      acetylated L-phenylalanine and L-tyrosine methyl ester hydrolysis.

PMID- 22142733
TI  - Enzyme-assisted extraction of lycopene from tomato processing waste.
AB  - A central composite design was used to optimize the enzyme-assisted extraction of
      lycopene from the peel fraction of tomato processing waste. Tomato skins were
      pretreated by a food-grade enzyme preparation with pectinolytic and cellulolytic
      activities and then subjected to hexane extraction. The factors investigated
      included extraction temperature (10-50  degrees C), pretreatment time (0.5-6.5
      h), extraction time (0.5-4.5 h), enzyme solution-to-solid ratio (10-50 dm3/kg)
      and enzyme load (0-0.2 kg/kg). Overall, an 8- to 18-fold increase in lycopene
      recovery was observed compared to the untreated plant material. From a response
      surface analysis of the data, a second-degree polynomial equation was developed
      which provided the following optimal extraction conditions: T=30  degrees C,
      extraction time=3.18 h and enzyme load=0.16 kg/kg. The obtained results strongly
      support the idea of using cell-wall degrading enzymes as an effective means for
      recovering lycopene from tomato waste.

PMID- 22142734
TI  - Selection of commercial hydrolytic enzymes with potential antifouling activity in
      marine environments.
AB  - In this work, the marine antifouling potential of some commercially available
      hydrolytic enzymes acting on the main constituents of extracellular polymeric
      substances (EPS) involved in bacterial biofilm formation was determined. The
      selected protease (i.e., alpha-chymotrypsin from bovine pancreas), carbohydrase
      (i.e., alpha-amylase from porcine pancreas) and lipase (from porcine pancreas)
      exhibited remarkable hydrolytic activities towards target macromolecules
      typically composing EPS under a wide range of pHs (6.5-9.0 for alpha-chymotrysin
      and alpha-amylase; 7.0-8.5 for the lipase) and temperatures (from 10  degrees C
      to 30  degrees C), as well as relevant half-lives (from about 2 weeks to about 2
      months), in a marine synthetic water. The activity displayed by each enzyme was
      poorly affected by the co-presence of the other enzymes, thus indicating their
      suitability to be employed in combination. None of the enzymes was able to
      inhibit the formation of biofilm by an actual site marine microbial community
      when applied singly. However, a mixture of the same enzymes reduced biofilm
      formation by about 90% without affecting planktonic growth of the same microbial
      community. This indicates that multiple hydrolytic activities are required to
      efficiently prevent biofilm formation by complex microbial communities, and that
      the mixture of enzymes selected in this study has the potential to be employed as
      an environmental friendly antifouling agent in marine antifouling coatings.

PMID- 22142735
TI  - Characterization and optimization of beta-galactosidase immobilization process on
      a mixed-matrix membrane.
AB  - beta-Galactosidase is an important enzyme catalyzing not only the hydrolysis of
      lactose to the monosaccharides glucose and galactose but also the
      transgalactosylation reaction to produce galacto-oligosaccharides (GOS). In this
      study, beta-galactosidase was immobilized by adsorption on a mixed-matrix
      membrane containing zirconium dioxide. The maximum beta-galactosidase adsorbed on
      these membranes was 1.6 g/m2, however, maximal activity was achieved at an enzyme
      concentration of around 0.5 g/m2. The tests conducted to investigate the optimal
      immobilization parameters suggested that higher immobilization can be achieved
      under extreme parameters (pH and temperature) but the activity was not retained
      at such extreme operational parameters. The investigations on immobilized enzymes
      indicated that no real shift occurred in its optimal temperature after
      immobilization though the activity in case of immobilized enzyme was better
      retained at lower temperature (5  degrees C). A shift of 0.5 unit was observed in
      optimal pH after immobilization (pH 6.5 to 7). Perhaps the most striking results
      are the kinetic parameters of the immobilized enzyme; while the Michaelis
      constant (K(m)) value increased almost eight times compared to the free enzyme,
      the maximum enzyme velocity (V(max)) remained almost constant.

PMID- 22142737
TI  - Phylogenetics of Anthyllis (Leguminosae: Papilionoideae: Loteae): Partial
      incongruence between nuclear and plastid markers, a long branch problem and
      implications for morphological evolution.
AB  - Phylogenetic relationships in the genus Anthyllis (Leguminosae: Papilionoideae:
      Loteae) were investigated using data from the nuclear ribosomal internal
      transcribed spacer regions (ITS) and three plastid regions (psbA-trnH intergenic
      spacer, petB-petD region and rps16 intron). Bayesian and maximum parsimony (MP)
      analysis of a concatenated plastid dataset recovered well-resolved trees that are
      topologically similar, with many clades supported by unique indels. MP and
      Bayesian analyses of the ITS sequence data recovered trees that have several well
      supported topological differences, both among analyses, and to trees inferred
      from the plastid data. The most substantial of these concerns A. vulneraria and
      A. lemanniana, whose placement in the parsimony analysis of the ITS data appears
      to be due to a strong long-branch effect. Analysis of the secondary structure of
      the ITS1 spacer showed a strong bias towards transitions in A. vulneraria and A.
      lemanniana, many of which were also characteristic of certain outgroup taxa. This
      may contribute to the conflicting placement of this clade in the MP tree for the
      ITS data. Additional conflicts between the plastid and ITS trees were more
      taxonomically focused. These differences may reflect the occurrence of reticulate
      evolution between closely related species, including a possible hybrid origin for
      A. hystrix. The patterns of incongruence between the plastid and the ITS data
      seem to correlate with taxon ranks. All of our phylogenetic analyses supported
      the monophyly of Anthyllis (incl. Hymenocarpos). Although they are often
      taxonomically associated with Anthyllis, the genera Dorycnopsis and Tripodion are
      shown here to be more closely related to other genera of Loteae. We infer up to
      six major clades in Anthyllis that are morphologically well-characterized, and
      which could be recognized as sections. Four of these agree with various
      morphology-based classifications, while the other two are novel. We reconstruct
      the evolution of several morphological characteristics found only in Anthyllis or
      tribe Loteae. Some of these characters support major clades, while others show
      evidence of homoplasy within Anthyllis.

PMID- 22142738
TI  - Phylogeny of Cercis based on DNA sequences of nuclear ITS and four plastid
      regions: implications for transatlantic historical biogeography.
AB  - The disjunct genus Cercis has been used to test models of Northern Hemisphere
      historical biogeography. Previous phylogenetic estimates employing DNA sequences
      of the ITS region and (in one study) those of ndhF recovered a well supported
      clade of North American and western Eurasian species that was nested within a
      paraphyletic group of Chinese species. Resolution and clade support within the
      tree were otherwise low and the monophyly of Cercis canadensis was uncertain.
      Here we conduct a phylogenetic analysis of Cercis with a higher number of regions
      (ITS, ndhF, rpoB-trnC, trnT-trnD, and trnS-trnG) and samples than in previous
      studies. Results corroborate the initial divergence between the Chinese species
      Cercis chingii and the rest of the genus. Support is newly found both for a clade
      of the two North American species as sister to the western Eurasian species, and
      for the monophyly of C. canadensis. As in a previous study, divergence between
      North American and western Eurasian Cercis was estimated as mid-Miocene (ca. 13
      million years ago), and the ancestor in which this divergence occurred was
      inferred to be xerophytic. Contrary to previous studies, however, our data infer
      strictly east-to-west vicariance. The timing of the transatlantic divergence in
      Cercis is too recent to be explained by a postulated continuous belt of semi-arid
      vegetation between North America and Europe in the Paleogene, suggesting instead
      the presence of a Miocene North Atlantic corridor for semi-arid plants. In the
      absence of strong evidence from other sources, the possibility that Cercis has
      been able to quickly adapt from mesophytic antecedents to semi-arid conditions
      whenever the latter have arisen in the Northern Hemisphere can be considered a
      plausible alternative, although parsimony optimization renders this scenario two
      steps longer.

PMID- 22142739
TI  - Mitochondrial phylogeny and biogeographic history of the Greek endemic land-snail
      genus Codringtonia Kobelt 1898 (Gastropoda, Pulmonata, Helicidae).
AB  - The aim of this work was to infer the phylogeny of the Greek endemic land-snail
      genus Codringtonia Kobelt 1898, estimate the time frame of the radiation of the
      genus, and propose a biogeographic scenario that could explain the contemporary
      distribution of Codringtonia lineages. The study took place in the districts of
      Peloponnese, Central Greece and Epirus of mainland Greece. Sequence data
      originating from three mtDNA genes (COI, COII, and 16S rDNA) were used to infer
      the phylogeny of the eight nominal Codringtonia species. Furthermore, the
      radiation time-frame of extant Codringtonia species was estimated using a relaxed
      molecular clock analysis and mtDNA substitution rates of land snails. The
      phylogenetic analysis supported the existence of six Codringtonia lineages in
      Greece and indicated that one nominal species (Codringtonia neocrassa) might
      belong to a separate genus distantly related to Codringtonia. The time frame of
      differentiation of Codringtonia species was placed in the Late Miocene
      Pleistocene epoch. The dispersal-vicariance analysis performed indicated that
      most probably Codringtonia exhibited a north-to-south spread with the ancestral
      area being that of central Greek mainland, accompanied with duplication
      (speciation) and vicariance events.

PMID- 22142741
TI  - The effect of valproic acid and oxcarbazepine on the distribution of adhesion
      molecules in embryo implantation.
AB  - This study was intended to investigate the effect of valproate (VPA) and
      oxcarbazepine (OXC) on embryo implantation in terms of extracellular matrix
      protein distribution. Thirty female rats (Wistar albino) were assigned to three
      groups of 10 animals each. Group 1 was administered two doses of saline solution,
      group 2, two doses of VPA at 300 mg/kg/day and group 3, two doses of OXC at
      100mg/kg/day, for a period of 3 months. Female rats with vaginal plugs mated with
      males for one night were placed into separate cages. Day of mating was taken as
      day 0, and implantation areas were obtained with rats being sacrificed on the
      morning of day 7. Immunohistochemical staining and electron microscopic protocols
      were then applied. At electron microscopic evaluation, extraembryonic endoderm
      and ectoderm layers could not be distinguished in semi-thin sections in the VPA
      group, while they were partially differentiated in the OXC group. At
      immunohistochemical staining, laminin was observed in the primary embryonic
      endoderm cell visceral and parietal layers, the uterine luminal epithelial cells
      and the secondary decidual zone in the control group. In the VPA group, it was
      weakly expressed in some embryo trophoectoderm cells and uterine luminal
      epithelial cells and moderately in some decidual cells. In the OXC group, it was
      moderately expressed in some trophoectoderm and decidual cells. Collagen IV was
      localized in the ectoplacental cone cells and secondary decidual zone and weak in
      the luminal epithelial cells in the control group. In the VPA and OXC groups,
      collagen IV was negative in all embryonic and maternal structures in the VPA and
      OXC groups. Vimentin was moderately expressed in the luminal epithelium and
      strongly expressed in the primary decidual zone and ectoplacental cone cells in
      the control group. In the VPA group, it was negative in the embryo
      trophoectoderm, decidual and uterine luminal epithelial cells, while in the OXC
      group it was moderately localized in the ectoplacental cone cells. The use of VPA
      and OXC has a negative effect on the expression of extracellular matrix proteins
      that play a key role in embryo implantation in young rats. This may lead to
      pregnancies ending in failure.

PMID- 22142742
TI  - An introduction to common and uncommon clinical or metabolic diseases with
      rheumatic phenotypes.

PMID- 22142740
TI  - Early postural adjustments in preparation to whole-body voluntary sway.
AB  - We studied postural adjustments associated with a quick voluntary postural sway
      under two conditions, self-paced and simple reaction-time. Standing subjects were
      required to produce quick discrete shifts of the center of pressure (COP)
      forward. About 400-500ms prior to the instructed COP shift, there were deviations
      of the COP in the opposite direction (backwards) accompanied by changes in the
      activation levels of several postural muscles. Under the reaction-time
      conditions, the timing of those early postural adjustments did not change
      (repeated measures MANOVA: p>0.05) while its magnitude increased significantly
      (confirmed by repeated measures MANOVA: p<0.05). These observations are opposite
      to those reported for anticipatory postural adjustments under simple reaction
      time conditions (a significant change in the timing without major changes in the
      magnitude). We conclude that there are two types of feed-forward postural
      adjustments. Early postural adjustments prepare the body for the planned action
      and/or expected perturbation. Some of these preparatory actions may be
      mechanically necessary. Later, anticipatory postural adjustments generate net
      forces and moments of force acting against those associated with the expected
      perturbation. Both types of adjustments fit well the referent configuration
      hypothesis, which offers a unified view on movement-posture control.

PMID- 22142743
TI  - Miscellaneous non-inflammatory musculoskeletal conditions. Musculoskeletal
      conditions associated with Wilson's disease.
AB  - Wilson's disease (WD) is a rare disease, defined as an autosomal recessive
      disorder characterised by release of free copper and dramatic accumulation of
      intracellular hepatic copper with subsequent hepatic and central nervous system
      abnormalities. Mutations of the ATP7B gene are responsible for the metabolic
      dysfunction. Small open studies have reported spinal radiological abnormalities
      including scoliosis, diffuse bone demineralisation, osteochondritis and
      occasionally fracture. Prevalence of osteoporosis in young adult patients is
      debated, ranging from 10%, with normal mean Z-score values, to 43% in adults.
      Past history of spinal or peripheral fractures might be present in 50% of
      patients. Articular disorders include arthralgias of large joints, such as knee
      pain, rare effusions, early onset of radiological features of osteoarthritis and
      associated osteochondritis of the knee joint. Radiological chondrocalcinosis, an
      unusual feature in young adults, has to be confirmed. Few patients may develop
      drug-induced lupus with arthralgias, positive anti-nuclear and anti-histone
      antibodies, secondary to D-penicillamine, the major copper chelator used in WD.
      In this orphan disease, small retrospective studies cannot allow ascertaining
      definite WD-related articular and bone manifestations. However, such clinical and
      radiological abnormalities are occasionally the first symptoms leading to
      diagnosis. Physicians should be aware that unexplained joint pain and effusion,
      or even radiological features of osteoarthritis, of the large joints in
      adolescents could suggest WD and lead to copper survey.

PMID- 22142744
TI  - Miscellaneous non-inflammatory musculoskeletal conditions. Bartter's and
      Gitelman's diseases.
AB  - Bartter's and Gitelman's syndromes are two different genetic renal diseases, but
      are both characterised by hypokalaemia and metabolic alkalosis. Bartter's
      syndrome is characterised by multiple gene mutations (Na-K-2Cl cotransporter;
      K(+) channels renal outer medullary potassium channel (ROMK); Cl channels,
      chloride channel Kb (ClCNKb); regulatory protein Barttin; and Ca(2+) -sensing
      receptor, CaSR) at the thick ascending limb of Henle's loop, while Gitelman's
      syndrome is caused by a mutation in the gene encoding the renal thiazide
      sensitive Na(+)-Cl(-) cotransporter, located in the apical membrane of the distal
      convoluted tubule. The co-existence of hypokalaemia with hypomagnesaemia and
      hypocalciuria represents the biochemical hallmark of Gitelman's syndrome that
      distinguishes it from Bartter's syndrome. Calcium pyrophosphate deposition (CPPD)
      including chondrocalcinosis has been frequently reported in association with
      Bartter's syndrome. Some authors postulate that these cases were probably due to
      Gitelman's syndrome and not due to Bartter's syndrome as all patients had
      hypomagnesaemia. This electrolyte disorder seems to induce CCP crystal
      deposition. To date, no cases of CPPD have been reported in patients who had
      Bartter's syndrome without hypomagnesaemia. CPPD may be found in other conditions
      associated with hypomagnesaemia, such as short bowel syndrome or tacrolimus
      therapy in liver transplantation patients. As acute CPP crystal arthropathy or
      pseudogout can be the onset presentation of Gitelman's syndrome, CPPD should be
      considered a major feature of this disease. Rheumatologists should be aware of
      the association between Gitelman's syndrome and CPPD, and should consider this
      metabolic disorder when CPPD occurs in younger patients.

PMID- 22142745
TI  - Miscellaneous non-inflammatory musculoskeletal conditions. Haemochromatosis: the
      bone and the joint.
AB  - Genetic haemochromatosis is a hereditary disease characterised by tissue iron
      overload. In Caucasians it is most often due to homozygous C282Y HFE gene
      mutation, but other genes may be involved. Without treatment by venesections,
      patients can develop life-threatening visceral damage such as liver cirrhosis and
      carcinoma, diabetes or heart failure. This treatment has been remarkably
      successful in preventing these complications, but patients survive with other
      symptoms of the disease susceptible to impair, sometimes seriously, their quality
      of life. This is the case of arthropathy and osteoporosis complicating
      haemochromatosis. In this chapter, focus has been placed on the rheumatological
      complications of genetic haemochromatosis.

PMID- 22142746
TI  - Miscellaneous non-inflammatory musculoskeletal conditions. Gaucher disease and
      bone.
AB  - Gaucher disease (GD) is an inherited lysosomal storage disorder affecting
      multiple organs. Non-neuronopathic GD, the most common form, can present with
      hepatosplenomegaly, anaemia, bleeding tendencies, thrombocytopenia, skeletal
      pathologies, growth retardation and, in severe cases, with pulmonary disease. The
      bone manifestations include bone infarcts, avascular bone necrosis, lytic
      lesions, osteosclerosis, fractures due to osteoporosis and, rarely, acute
      osteomyelitis. Bone pain of varying intensity, fractures and joint collapses
      increase the patients' morbidity and impair their mobility and quality of life.
      Currently available therapies - enzyme replacement therapy and substrate
      reduction therapy - have shown to improve blood count and the visceral
      manifestations within a short time. Beneficial effects have also been documented
      on bone pain, bone crises and the extent of osteoporosis. The article focusses on
      the bone pathologies of GD including its pathophysiology, current diagnostics,
      clinical management and therapeutic effects of enzyme replacement therapy,
      substrate reduction therapy and bone-specific therapies.

PMID- 22142747
TI  - Miscellaneous non-inflammatory musculoskeletal conditions. Rare thesaurismosis
      and xanthomatosis.
AB  - The focus will be on xanthomatosis, a tissue danger signal which needs to be
      recognized by the clinician, and its relationship with monogenetic lipoprotein
      disorders (cholesterol, triglycerides), bile acid and sterol metabolism,
      particularly on metabolic pathways and genetics as well as on musculoskeletal and
      cardiovascular involvement, and their implications for clinical management. The
      critical question is to assess coronary heart disease risk, requiring correct
      identification of the pattern of lipoprotein disorders and of the causes (primary
      or secondary). Familial hypercholesterolemia must be suspected in adults and
      children with raised total cholesterol, especially when there is a personal or a
      family history of premature coronary heart disease, usually requiring potent
      statins to achieve adequate LDL-cholesterol lowering, even if we do not know
      safety of long-term therapy and whether treatments of dyslipidemia early in life
      prevent cardiovascular diseases in adulthood. Cerebrotendinous xanthomatosis is a
      treatable disease and must be suspected if there is a history of infantile
      chronic diarrhea and/or juvenile cataracts, even in the absence of tendon
      xanthomas. Current evidence for the prevention and screening, diagnosis, and
      treatment of dyslipidemia are available for the clinicians.

PMID- 22142748
TI  - Miscellaneous non-inflammatory musculoskeletal conditions. Blau syndrome.
AB  - Blau syndrome (BS) is a rare dominantly inherited, inflammatory syndrome
      characterised by the clinical triad of granulomatous dermatitis, symmetric
      arthritis and recurrent uveitis. The caspase recruitment domain gene CARD15/NOD2
      has been identified as the gene responsible for BS. In the majority of patients,
      the disease is characterised by early onset, usually before 3-4 years of age.
      Onset is most often articular and cutaneous. Eye symptoms usually start later;
      however, eye involvement is the most relevant morbidity of BS. Atypical cases of
      BS have been reported with involvement of organs other than skin, joint and eyes.
      Due to its rarity and the variations in the severity and evolution of its
      expressions, there have been no studies on the optimal treatment for patients
      with BS. If the therapeutic response to corticosteroids is unsatisfactory,
      additional treatment with immunosuppressive agents should be tried. The results
      with biologic anti-cytokine agents, such as infliximab and anakinra, are
      variable, particularly with regard to ocular morbidity. This review will focus on
      the clinical and genetics aspects of the familial and the sporadic form of BS.
      Further, we will describe an Italian family followed by us over the past 25
      years.

PMID- 22142749
TI  - Miscellaneous non-inflammatory musculoskeletal conditions. Jaccoud's arthropathy.
AB  - Jaccoud's arthropathy (JA) is a condition characterised clinically by
      'reversible' joint deformities such as swan neck, thumb subluxation, ulnar
      deviation, 'boutonniere' and hallux valgus, along with an absence of articular
      erosions on a plain radiograph. JA was initially described in patients with
      rheumatic fever (RF), but as this disorder has become rare the main clinical
      entity associated to JA at present is systemic lupus erythematosus (SLE). JA has
      also been described in other connective tissue diseases, infections and
      neoplasia. In general, its prevalence in either SLE or RF is around 5%. The
      etiopathogenic mechanisms of JA are not known, but some authors have suggested an
      association with hypermobility syndrome. Several studies have attempted to
      identify an association of different antibodies with JA in SLE patients, but
      their findings do not allow for the drawing of any definite conclusions. Newer
      imaging techniques such as magnetic resonance and high-performance
      ultrasonography have revealed the presence of small erosions in joints of a few
      patients with JA. Presently, the therapy for JA is conservative and based on the
      use of non-hormonal anti-inflammatory drugs, low doses of corticosteroids,
      methotrexate and antimalarials. The role of surgery through either the
      realignment of soft tissue around the joint--or more aggressive procedures such
      as arthrodesis, silastic implant and arthroplasty--needs to be proven.

PMID- 22142750
TI  - Miscellaneous non-inflammatory musculoskeletal conditions. Pachydermoperiostosis.
AB  - Pachydermoperiostosis (PDP), also known as primary hypertrophic osteoarthropathy,
      is a rare disease of the skin and bones that has clear genetic predisposition and
      well-defined clinical features. PDP is characterised by the presence of exuberant
      skin hypertrophy that, at the most distal parts of the extremities, takes a
      drumstick configuration. This deformity is conventionally known as digital
      clubbing. In advanced stages, skin hypertrophy may also be present in the head
      with furrowing of the facial features and eyelids ptosis. Another characteristic
      feature of the disease is periosteal proliferation of the long bones. Abnormal
      vascular endothelial growth factor and/or genetically determined prostaglandins
      overexpression may play a key role on its pathogenesis. No therapy has been shown
      to be effective in reversing hypertrophic changes. When bone pain is present, non
      steroidal anti-inflammatory drugs are frequently useful. Isolated case reports
      have described that bisphosphonates may ease recalcitrant bone pain.

PMID- 22142752
TI  - Why do young people start drinking? Motives for first-time alcohol consumption
      and links to risky drinking in early adolescence.
AB  - AIMS: To investigate which motives young adolescents indicate for first-time
      alcohol consumption and whether these motives are linked to risky drinking.
      METHODS: Logistic regressions were used based on a nationally representative
      sample of 1,654 11- to 14-year-olds who had consumed alcohol at least once.
      RESULTS: 'To toast' (42.5%), 'to find out what effect it would have' (36.4%), and
      'to have more fun at a party' (31.0%) were most frequently indicated as motives.
      Boys indicated curiosity about the effect more often than girls who instead more
      frequently indicated coping motives. Those who had their first drink 'to have
      more fun at a party' or 'because it was exciting' had a higher likelihood of
      risky drinking. Moreover, those who indicated depression as a motive were three
      times more likely to have 5 or more drinks on a single occasion. CONCLUSIONS:
      Information on young people's motives for first-time drinking appears to play a
      significant role in primary prevention, e.g. to prevent risky drinking or alcohol
      related problems later in life by postponing alcohol use.

PMID- 22142753
TI  - Neuropsychological, medical and rehabilitative management of persons with
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic and disabling disease that attacks the
      central nervous system (CNS). The symptoms, progression, and severity of the
      disease are unpredictable and vary from one person to another. Major symptoms
      include fatigue, sensory-motor (e.g., visual disturbance, spasticity,
      locomotion), cognitive (e.g., decreased information processing speed, impaired
      memory), and psychiatric problems (e.g., depression). Although the etiology is
      unknown, MS is thought to be an autoimmune disease triggered by a viral or other
      infectious agent in genetically susceptible individuals. The CNS target of the
      disease is myelin, although it is now known that other aspects of the CNS such as
      axonal and gray matter regions are also involved.

PMID- 22142751
TI  - Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic
      familial tumoral calcinosis (FGF23, GALNT3 and alphaKlotho).
AB  - Familial tumoral calcinosis (TC) is a rare disorder distinguished by the
      development of ectopic and vascular calcified masses that occur in settings of
      hyperphosphatemia (hFTC) and normophosphatemia (nFTC). Serum phosphorus
      concentrations are relatively tightly controlled by interconnected endocrine
      activity at the level of the intestine, kidney, and skeleton. Discovering the
      molecular causes for heritable forms of hFTC has shed new light on the regulation
      of serum phosphate balance. This review will focus upon the genetic basis and
      clinical approaches for hFTC, due to genes that are related to the phosphaturic
      hormone fibroblast growth factor-23 (FGF23). These include FGF23 itself, an FGF23
      glycosylating enzyme (GALNT3), and the FGF23 co-receptor alpha-Klotho (alphaKL).
      Our understanding of the molecular basis of hFTC will, in the short term, aid in
      understanding normal phosphate balance, and in the future, provide potential
      insight into the design of novel therapeutic strategies for both rare and common
      disorders of phosphate metabolism.

PMID- 22142754
TI  - Dissimilar outcomes of apparently similar procedures as a challenge to clinical
      neurorehabilitation and basic research: when the same is not the same.
AB  - In the study of the brain and how it adapts to changes or injury, researchers
      sometimes come across situations where apparently similar types of tests or
      training do not achieve similar outcome results. This is true, in particular,
      within the field of computer-based rehabilitation where paper-and-pencil tests
      and training is converted to computer. This paper raises the attention to the
      fact that supposedly similar settings may not, in fact, elicit similar results
      and caution therapists and researchers who work with rehabilitation of brain
      injury. The paper suggests that the underlying mechanisms behind this may be
      illuminated by using the REF (Reorganization of Elementary Functions) model and
      suggests that further research into the use of advanced technologies such as
      computer-generated virtual reality is required.

PMID- 22142755
TI  - Critical illness polyneuropathy: a case report.
AB  - Critical illness polyneuropathy (CIP) is defined as a common complication of
      critically ilness patients who were admitted to the intensive care unit due to
      sepsis, multiple trauma and/or multi-organ failure. We aimed to present a patient
      who was diagnosed as CIP. He was admitted to our outpatient clinic due to
      weakness and pain in his lower extremities. He had been followed in an intensive
      care unit due to suicid five months ago. There were symmetrically and
      predominantly muscle weakness, sensory impairment, absence of deep tendon
      reflexes in his lower extremities. Electrophysiological evaluation demonstrated
      motor and sensory axonal distal polyneuropathy predominantly in lower
      extremities. At follow up, he had high fever, and elevated acute phase responses.
      Therefore source of infection was investigated and was suspected to a diagnosis
      of infective endocarditis. He was discharged to be hospitalized in cardiology
      clinic. With this case, we think that physiatrists should take into consideration
      a diagnosis of critical illness polyneuropathy in patients with symmetric motor
      weakness. In CIP, muscle weakness, sensory loss, neuropathic pain, and autonomic
      problems lengthened the rehabilitation period. Due to a diagnosis of infective
      endocarditis in our case, we point out that source of infection should be
      carefully investigated if there is acute phase responses in CIP patients even if
      during rehabilitation period.

PMID- 22142756
TI  - Changes in gait patterns with rhythmic auditory stimulation in adults with
      cerebral palsy.
AB  - The objective is to evaluate the changes in gait patterns with rhythmic auditory
      stimulation (RAS) in adults with cerebral palsy (CP). Fourteen CP with bilateral
      spasticity participated in this study. A repeated-measures analysis of gait was
      performed in the presence and absence of RAS. Thirty healthy controls were also
      recruited. Each subject walked 10 m at their comfortable walking speed.
      Temporospatial data and kinematic parameters of gait were analyzed without RAS
      and with RAS. RAS was provided using a combination of a metronome beat set to the
      individual's cadence and rhythmic cueing from a live keyboard playing. Kinematic
      parameters, gait deviation index (GDI) as a measure of overall gait pathology,
      and asymmetry of temporospatial data were assessed. Gait analysis revealed that
      anterior tilt of pelvis and hip flexion during a gait cycle was significantly
      changed with RAS (p < 0.05), whereas there were no statistical differences in
      knee, ankle, and foot kinematic parameters. Additionally, the GDI exhibited a
      modest, but a statistically significant, improvement with RAS (p < 0.05). Based
      on ambulatory status, household ambulators showed that side-to-side asymmetry of
      step length as well as the GDI was significantly attenuated with RAS (p < 0.05).
      Walking with RAS resulted in kinematic changes of the pelvic and hip movement in
      spastic CP. Especially, the application of RAS immediately ameliorated overall
      gait pathology as well as temporospatial asymmetry in household ambulators.
      Therefore, RAS may be one of the therapeutic tools for gait training in adults
      with CP.

PMID- 22142757
TI  - Recovery of the corticospinal tract after injury by transtentorial herniation: a
      case report.
AB  - Little is known about recovery of the corticospinal tract (CST) after injury by
      transtentorial herniation (TH). We present with a patient who showed recovery of
      the CST after injury by TH, using diffusion tensor tractography (DTT) and
      transcranial magnetic stimulation (TMS). A 69-year-old female underwent
      craniotomy and drainage of an intracerebral hemorrhage in the left corona radiata
      and basal ganglia. Brain CT showed left TH and brain MRI revealed a leukomalactic
      lesion at the left cerebral peduncle. The patient presented with complete
      paralysis of the right extremities at ICH onset, but slowly recovered some
      function to the point of being able to move the affected extremities against
      gravity at about 6 months after onset. Three-week DTT showed disruption of the
      left CST below the cerebral peduncle; however, this disruption was recovered on 1
      year DTT. Three-week TMS showed no motor evoked potential for the affected
      hemisphere; in contrast, motor evoked potentials that were compatible with
      regenerated CST were obtained from the affected hand muscle at 6 months. Using
      DTT and TMS in a patient with ICH, we demonstrated recovery of the CST after
      injury by TH.

PMID- 22142758
TI  - Effects of levodopa on forward and backward gait patterns in persons with
      Parkinson's disease.
AB  - INTRODUCTION: Backward walking is difficult for persons with Parkinson's disease
      (PD). It is unknown how levodopa influences backward gait patterns, especially
      when compared to forward gait patterns. PURPOSE: Investigate the effects of
      levodopa on forward and backward gait patterns in individuals with PD. DESIGN: A
      repeated measures design was used. METHODS: The sample consisted of 21
      individuals with PD (15 males, 6 females). Their mean age was 70.24 +/- 8.69 yr.
      The average time since diagnosis was 11.81 +/- 5.49 years. The median of the
      Hoehn and Yahr stage while 'ON' medication was 2.57. Gait patterns during forward
      and backward walking at a self-selected comfortable speed were recorded before
      and after taking levodopa on the same day. RESULTS: Levodopa significantly
      increased gait speed and stride length and decreased the percent of the gait
      cycle (%GC) spent in double support. Gait speed and stride length were greater
      and the %GC spent in double support was less during forward walking compared with
      backward walking. Cadence was not changed by levodopa or walking direction.
      CONCLUSIONS: Levodopa improved gait characteristics during backward walking in a
      manner similar to that during forward walking in persons with PD.

PMID- 22142759
TI  - Different cortical activation patterns during voluntary eccentric and concentric
      muscle contractions: an fMRI study.
AB  - Concentric and eccentric muscle contractions have distinct differences in their
      neuromuscular and neurophysiologic characteristics. However, although many
      evidences regarding the features of these types of muscle contraction have
      emerged, there have been few neuroimaging studies to compare the two types of
      contractions. Therefore, we investigated whether cortical activity associated
      with eccentric contraction of the wrist extensors differed from that of
      concentric contraction, using functional MRI (fMRI). Fifteen right-handed healthy
      subjects were enrolled in this study. During 4 repeating blocks of eccentric and
      concentric muscle contraction paradigms, the brain was scanned with fMRI. The
      differences in the BOLD signal intensities during the performance of eccentric
      and concentric exercise were compared in the predetermined regions of interest.
      Our findings revealed that many cortical areas associated with motor performance
      were activated, including the primary motor area, the inferior parietal lobe, the
      pre-supplementary area (pre-SMA), the anterior cingulate cortex, the prefrontal
      area, and the cerebellum. In addition, lower signal intensities were seen in the
      right primary motor cortex and right cerebellum during eccentric contractions
      compared with concentric contractions, whereas higher signal intensities were
      detected in other cortical areas during eccentric contractions. In the study, we
      demonstrated that eccentric and concentric muscle contractions induced quite
      different patterns of cortical activity respectively. These findings might be
      attributed to different strategy of neuro-motor processing and a higher level of
      cognitive demand for the performance of motor task with a higher degree of
      difficulty such as that required during eccentric contractions in comparison of
      concentric contractions.

PMID- 22142760
TI  - The effects of spinal cord injury and exercise on bone mass: a literature review.
AB  - INTRODUCTION: Bone loss is a common and often debilitating condition that
      accompanies spinal cord injury. Because bone loss after spinal cord injury is
      multifactorial, it can be difficult to assess and treat. This process becomes
      even more complex as secondary conditions associated with aging are introduced.
      PURPOSE: There are two purposes of this literature review. The first is to
      summarize information concerning the mechanisms of bone loss and osteoporosis
      after spinal cord injury. The second is to summarize existing data concerning the
      effects of exercise on bone loss after spinal cord injury. METHOD: Literature was
      reviewed concerning the bone loss process and the non-pharmacological treatment
      options for ameliorating bone loss after spinal cord injury. RESULTS: (Part One)
      Osteoporosis is universal in persons with chronic complete spinal cord injury,
      which increases the risk of bone fracture. Bone loss after spinal cord injury is
      both sublesional and regional with the greatest areas of bone demineralization
      being in the sublesional trabecular laden areas of the distal and proximal
      epiphyses of the femur and tibia. (Part Two) While passive weight bearing of
      paralyzed lower extremities appears to be ineffective, stressing the bones
      through muscular contractions initiated by electrical stimulation (FES) have
      yielded positive results in some cases. The intensity, frequency, and duration of
      stress to the bones appear to be important determinants of improved bone
      parameters. Although further quantification of these components is needed, some
      generalized guidelines can be deduced from completed research. Intensities
      showing positive results have been loads of one to one and a half times body
      weight for FES exercise or having participants FES cycle at their highest power
      output. Safety precautions must be used to decrease risk of bone fracture.
      Generally, the frequency is effective with three or more weekly exercise
      sessions. Studies of duration suggest that several months to one or more years of
      FES are necessary. DISCUSSION: In order to promote healthy and independent aging
      in patients with spinal cord injury, it is important to understand the processes,
      consequences and effective treatments involved with bone loss.

PMID- 22142761
TI  - Cortical reorganization of hand motor function to face somatotopy in a patient
      with brain injury: a functional MRI study.
AB  - We report on a patient with a meningioma whose hand motor function appeared to be
      reorganized mainly into the face somatotopy of the primary motor cortex (M1)
      following meningioma removal, using functional RMI (fMRI). A 76-year-old right
      handed woman showed leukomalactic lesions in the left fronto-parietal lobes and
      subcortical white matter, including the upper portion of the precentral knob
      after meningioma removal. She recovered motor function to the point that she was
      able to extend the affected fingers against gravity at 6 weeks and extend the
      affected fingers against resistance at 12 weeks. The right primary sensori-motor
      cortex centered on the precentral knob was activated during movement of the
      unaffected (left) hand. By contrast, the face somatotopy and inferior portion of
      the precentral knob of the left primary motor cortex were activated during
      movement of the right hand. Peak activations were present at the left face
      somatotopy of the primary motor cortex during movement of the right hand and the
      right precentral knob during movement of the left hand. Motor function of the
      affected hand appeared to be reorganized mainly into the face somatotopy of the
      primary motor cortex and partially into the lower portion of the precentral knob
      after meningioma removal.

PMID- 22142762
TI  - Do racial and ethnic minority patients fare worse after SCI?: a critical review
      of the literature.
AB  - A number of researchers have identified differences in SCI outcomes between
      racial and ethnic groups, but findings have never been synthesized to give
      clinicians and researchers a coherent picture of the problem. The goals of the
      current project were to (1) conduct a critical literature review of studies
      specifically investigating racial and ethnic disparities in spinal cord injury
      care, services, and outcomes; (2) explore possible causative factors that may
      explain these disparities; (3) propose strategies that may reduce disparities and
      improve access, service, and outcomes for minority patients with SCI; and (4)
      generate ideas for future research in this area. A search using MEDLINE/PubMed,
      PsycINFO, CINAHL, and HealthSource resulted in 49 articles discussing hospital,
      mental health, physical functioning, employment, quality of life, and family
      outcomes. Results indicated that after an SCI, racial and ethnic minority groups
      have shorter hospital lengths of stay, higher rehospitalizations rates, higher
      levels of depression, more days in poor health, greater degrees of unemployment,
      more difficulties with mobility, lower self-reported subjective well-being and
      quality of life and life satisfaction, and greater risk of marital breakup. A
      variety of causative factors, intervention strategies, and directions for future
      research are presented.

PMID- 22142763
TI  - Learning by observation and guidance in patients with Alzheimer's dementia.
AB  - How people suffering from dementia can be taught new motor skills for everyday
      household activities is an important but relatively unexplored area of research.
      Previous studies have demonstrated intact implicit learning abilities in patients
      with Alzheimer dementia (AD) on computerized motor-learning tasks and everyday
      activities, but explicit training strategies have been found to be beneficial in
      AD as well. The aim of the present study was to compare two explicit training
      methods, i.e. observational learning and learning by guidance, and an implicit
      training method in patients with AD and healthy controls. All three types of
      training methods resulted in statistically significant learning. However, while
      improvement from baseline was similar in both groups, the absolute performance of
      the patients in the explicit training methods was well below that of the
      controls. The modest success of the explicit training methods and the slightly
      better results achieved with the observation method should be investigated
      further in studies of the acquisition of everyday activities.

PMID- 22142764
TI  - The clinical application of the arcuate fasciculus for stroke patients with
      aphasia: a diffusion tensor tractography study.
AB  - Little is known about the clinical usefulness of diffusion tensor tractography
      (DTT) for the arcuate fasciculus (AF) in stroke patients with aphasia. Using DTT,
      we attempted to investigate the clinical usefulness of the AF in patients with
      aphasia. Five stroke patients and 7 age- and sex-matched normal subjects were
      recruited for this study. We recruited stroke patients with language dysfunction
      who had lesions in the left corona radiata and basal ganglia level. DTT for the
      AF was reconstructed using DTI-studio software. Korean-Western Aphasia Battery (K
      WAB) was used for measurement of language function. Patient 1, who showed mild
      dysarthria, revealed a normal left AF in terms of integrity and DTT parameters.
      In patient 2, with conduction aphasia, the left AF showed partial injury;
      however, the integrity of the left AF was spared. Patients 3 and 4, who had no
      brain lesions at Broca's area on conventional brain MRI, showed disruptions of
      the left AF over the stroke lesions after originating from Wernicke's area and
      they presented with Broca's aphasia. Patient 5 revealed global aphasia on K-WAB
      and the left AF was not reconstructed due to severe injury and Wallerian
      degeneration. We found that DTT for the AF could provide useful information on
      the presence or severity of injury of the AF, which could not be detected on
      conventional brain MRI in stoke patients. In addition, it could be helpful in
      classification of the aphasia type of stroke patients.

PMID- 22142765
TI  - The correlation of independency in activities of daily living performance with
      cognitive status and the intensity of neurological impairment in right-handed
      stroke patients.
AB  - PURPOSE: We aimed to investigate whether test performance in neurological and
      cognitive areas is able to predict daily task performance in stroke patients and
      if the two selected measures of stroke severity and cognitive function could be
      used as valid tools to predict functional outcomes after stroke. METHOD: We
      assessed 27 stroke patients (hemorrhagic and infarct) through Barthel Index (BI),
      Lowenstein Occupational Therapy Cognitive Assessment (LOTCA) and National
      Institute of Health Stroke Scale (NIHSS) in the first 6 months after stroke.
      RESULTS: The correlation of intensity of neurological impairment (NIHSS score)
      and ADL performance (BI score) was significant (P < 0/05), but we found no
      relation between general cognitive function (the total score of LOTCA) and
      individual independence (total score of BI). Although ADL performance areas
      associated with some cognitive components. CONCLUSION: The dependency after
      stroke is more affected by physical symptoms of stroke than by cognitive
      disorders. Moreover, the intensity of neurological impairment could be a better
      explanation for a patient's inability to perform basic ADL independently. Low
      direct relations in total scores of NIHS scale and BI was found, but LOTCA is not
      appropriate for prediction of independency in basic ADL performance after stroke.
      Nevertheless, further studies and confirmation are needed.

PMID- 22142766
TI  - Use of comparative genomics approaches to characterize interspecies differences
      in response to environmental chemicals: challenges, opportunities, and research
      needs.
AB  - A critical challenge for environmental chemical risk assessment is the
      characterization and reduction of uncertainties introduced when extrapolating
      inferences from one species to another. The purpose of this article is to explore
      the challenges, opportunities, and research needs surrounding the issue of how
      genomics data and computational and systems level approaches can be applied to
      inform differences in response to environmental chemical exposure across species.
      We propose that the data, tools, and evolutionary framework of comparative
      genomics be adapted to inform interspecies differences in chemical mechanisms of
      action. We compare and contrast existing approaches, from disciplines as varied
      as evolutionary biology, systems biology, mathematics, and computer science, that
      can be used, modified, and combined in new ways to discover and characterize
      interspecies differences in chemical mechanism of action which, in turn, can be
      explored for application to risk assessment. We consider how genetic, protein,
      pathway, and network information can be interrogated from an evolutionary biology
      perspective to effectively characterize variations in biological processes of
      toxicological relevance among organisms. We conclude that comparative genomics
      approaches show promise for characterizing interspecies differences in mechanisms
      of action, and further, for improving our understanding of the uncertainties
      inherent in extrapolating inferences across species in both ecological and human
      health risk assessment. To achieve long-term relevance and consistent use in
      environmental chemical risk assessment, improved bioinformatics tools,
      computational methods robust to data gaps, and quantitative approaches for
      conducting extrapolations across species are critically needed. Specific areas
      ripe for research to address these needs are recommended. 

PMID- 22142767
TI  - Inverse association between trans isomeric and long-chain polyunsaturated fatty
      acids in pregnant women and their newborns: data from three European countries.
AB  - BACKGROUND: trans unsaturated fatty acids are thought to interfere with essential
      fatty acid metabolism. To extend our knowledge of this phenomenon, we
      investigated the relationship between trans isomeric and long-chain
      polyunsaturated fatty acids (LCPUFA) in mothers during pregnancy and in their
      infants at birth. METHODS: Fatty acid composition of erythrocyte
      phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined in
      Spanish (n = 120), German (n = 78) and Hungarian (n = 43) women at the 20th and
      30th week of gestation, at delivery and in their newborns. RESULTS: At the 20th
      week of gestation, the sum of trans fatty acids in PE was significantly (p <
      0.01) lower in Hungarian [0.73 (0.51), % wt/wt, median (IQR)] than in Spanish
      [1.42 (1.36)] and German [1.30 (1.21)] women. Docosahexaenoic acid (DHA) values
      in PE were significantly (p < 0.01) higher in Hungarian [5.65 (2.09)] than in
      Spanish [4.37 (2.60)] or German [4.39 (3.3.2)] women. The sum of trans fatty
      acids significantly inversely correlated to DHA in PCs in Spanish (r = -0.37, p <
      0.001), German (n = -0.77, p < 0.001) and Hungarian (r = -0.35, p < 0.05) women,
      and in PEs in Spanish (r = -0.67, p < 0.001) and German (r = -0.71, p < 0.001),
      but not in Hungarian (r = -0.02) women. Significant inverse correlations were
      seen between trans fatty acids and DHA in PEs at the 30th week of gestation (n =
      241, r = -0.52, p < 0.001), at delivery (n = 241, r = -0.40, p < 0.001) and in
      cord lipids (n = 218, r = -0.28, p < 0.001). CONCLUSION: Because humans cannot
      synthesize trans isomeric fatty acids, the data obtained in the present study
      support the concept that high maternal trans isomeric fatty acid intake may
      interfere with the availability of LCPUFA both for the mother and the fetus.

PMID- 22142768
TI  - Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis.
AB  - Tumor therapy requires multi-functional treatment strategies with specific
      targeting of therapeutics to reduce general toxicity and increase efficacy. In
      this study we fabricated and functionally tested aptamer-conjugated and
      doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid
      perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c
      aptamers provided the ability to specifically target CCRF-CEM cells for both
      imaging and therapy. High-intensity focused ultrasound (HIFU) was introduced to
      trigger targeted acoustic droplet vaporization (ADV) which resulted in both
      mechanical cancer cell destruction by inertial cavitation and chemical treatment
      through localized drug release. HIFU insonation showed a 56.8% decrease in cell
      viability with aptamer-conjugated droplets, representing a 4.5-fold increase in
      comparison to non-conjugated droplets. In addition, the fully-vaporized droplets
      resulted in the highest DOX uptake by cancer cells, compared to non-vaporized or
      partially vaporized droplets. Optical studies clearly illustrated the transient
      changes that occurred upon ADV of droplet-targeted CEM cells, and B-mode
      ultrasound imaging revealed contrast enhancement by ADV in ultrasound images. In
      conclusion, our fabricated droplets functioned as a hybrid chemical and
      mechanical strategy for the specific destruction of cancer cells upon ultrasound
      mediated ADV, while simultaneously providing ultrasound imaging capability.

PMID- 22142770
TI  - Stimulated release of photosensitizers from graft and diblock micelles for
      photodynamic therapy.
AB  - To understand the effect of photosensitizer (PS) release from graft copolymer
      based micelles in photodynamic therapy (PDT), the two pH-sensitive and non-pH
      sensitive graft copolymers, (poly(N-vinyly caprolactam)-g-poly(D,L-lactide) and
      poly(N-vinyly caprolactam-co-N-vinyl imidazole)-g-poly(D,L-lactide)), were
      synthesized and utilized for the encapsulation of protoporphyrin IX (PPIX) for in
      vitro and in vivo PDT studies. Photochemical internalization (PCI) was utilized
      to study the localization of pH- and non-pH-sensitive micelles uptake in the
      lysosome. After non-toxic light treatment, PPIX was found in the nucleus with pH
      sensitive micelles, while PPIX was still localized in the lysosomal organism with
      the non-pH-sensitive micelles, as observed by confocal microscopy. Because the
      formation of singlet oxygen was observed for the block and graft micelles,
      dramatic differences in the cell viability could be ascribed to the damage
      occurring at the region where the PPIX was located. An in vivo study revealed
      that PPIX-loaded graft and diblock micelles presented prolonged blood circulation
      and enhanced tumor targeting ability. The PPIX released from g-CIM micelles on
      tumor site was further proved by ex vivo confocal image. In addition, non-pH
      sensitive micelle-treated mice showed a better repression of tumor growth than
      PPIX-treated mice, which was likely due to the larger amount of PS localized in
      the tumor region still exhibiting therapeutic effects. Finally, effective PDT
      induced inhibition of tumor growth was found in pH-sensitive micelle-treated
      mice. This work provides insight into PS-loaded graft and diblock micelles for
      the PDT of tumors.

PMID- 22142771
TI  - DNA as molecular target of analogous palladium and platinum anti-Trypanosoma
      cruzi compounds: a comparative study.
AB  - In the search for drugs with anti-trypanosome activity, we had previously
      synthesized two series of platinum and palladium analogous compounds of the
      formula [M(II)Cl(2)(HL)], where HL were bioactive 5-nitrofuryl or 5
      nitroacroleine thiosemicarbazone derivatives. In this work, we thoroughly
      characterized [M(II)Cl(2)(HL)] complexes interaction with DNA by using different
      techniques: gel electrophoresis, DNA viscosity measurements, circular dichroism
      (CD) and atomic force microscopy (AFM). Electrophoresis results showed that all
      complexes induced a withdrawal of DNA superhelicity demonstrated by a decrease in
      electrophoretic mobility of supercoiled DNA form. This effect on migration was
      dependent on dose but also on the nature of both the metal and the ligand. In
      general, the effect produced by palladium complexes was significantly more
      intense than that observed for the corresponding platinum analogs. Differences
      between palladium and platinum complexes were also observed in CD experiments.
      While palladium complexes induce evident calf thymus (CT)-DNA profile changes
      compatible with B-DNA to Z-DNA conformational transition, no clear effect was
      observed for platinum ones. Additionally, AFM studies showed that changes in the
      shape of plasmid DNA, like supercoiling, kinks and thickness increase resulted
      more intense for the former. In addition, either Pd or Pt complexes increased the
      viscosity of CT DNA solutions in a concentration dependent manner. Although the
      nature of DNA interaction of both series of analogous palladium and platinum
      complexes seemed to be similar, an explanation for the observed differential
      intensity of the effect could be related to the known kinetic stability
      differences between palladium and platinum compounds.

PMID- 22142772
TI  - Suppression of nasopharyngeal carcinoma cell by targeting beta-catenin signaling
      pathway.
AB  - AIM: To investigate the role of beta-catenin in pathogenesis of nasopharyngeal
      carcinoma (NPC). METHODS: Cellular proliferation, apoptosis, matrix penetration
      assay, and western blotting were employed to determine cell biological changes in
      NPC cell lines transfected with beta-catenin siRNA. Immunohistochemistry staining
      was used to detect beta-catenin and Ki-67 expression in NPC tissue. RESULTS: beta
      Catenin was upregulated in NPC cell lines and tissues compared with chronic
      nasopharyngitis tissue. beta-Catenin knockdown dramatically inhibited cellular
      growth, migration and invasion, but induced apoptosis of NPC cells. Further study
      showed that downstream genes of beta-catenin signaling pathway including cyclin
      D1, c-Myc, MMP2 and MMP9 expression were suppressed in NPC cell lines transfected
      with beta-catenin siRNA. CONCLUSION: Targeting beta-catenin signaling pathway may
      be a noval strategy for NPC therapy.

PMID- 22142773
TI  - Reflexive attention in touch: an investigation of event related potentials and
      behavioural responses.
AB  - Exogenous attention has been extensively studied in vision but little is known
      about its behavioural and neural correlates in touch. To investigate this, non
      informative tactile cues were followed after 800 ms by tactile targets and
      participants either detected targets or discriminated their location. Responses
      were slowed for targets at cued compared to uncued locations (i.e. inhibition of
      return (IOR)) only in the detection task. Concurrently recorded ERPs showed
      enhanced negativity for targets at uncued compared to cued locations at the N80
      component and this modulation overlapped with the P100 component but only for the
      detection task indicating IOR may, if anything, be linked to attentional
      modulations at the P100. Further, cue-target interval analysis showed an enhanced
      anterior negativity contralateral to the cue side in both tasks, analogous to the
      anterior directed attention negativity (ADAN) previously only reported during
      endogenous orienting.

PMID- 22142774
TI  - Placental histopathology after Coxiella burnetii infection during pregnancy.
AB  - Symptomatic and asymptomatic Coxiella burnetii infection during pregnancy have
      been associated with obstetric complications. We described placental
      histopathology and clinical outcome of five cases with asymptomatic C. burnetii
      infection during pregnancy and compared these cases with four symptomatic cases
      from the literature. In contrast with the symptomatic cases, we did not observe
      necrosis or active inflammation in the placentas of the asymptomatic women.
      Obstetrical outcome was more favourable in the asymptomatic cases than in the
      symptomatic cases. Asymptomatic and symptomatic C. burnetii infection during
      pregnancy are different entities with respect to placental histopathology and the
      risk of obstetric complications.

PMID- 22142769
TI  - Enhancing the therapeutic efficacy of adenovirus in combination with
      biomaterials.
AB  - With the reason that systemically administered adenovirus (Ad) is rapidly
      extinguished by innate/adaptive immune responses and accumulation in liver, in
      vivo application of the Ad vector is strictly restricted. For achieving to
      develop successful Ad vector systems for cancer therapy, the chemical or physical
      modification of Ad vectors with polymers has been generally used as a promising
      strategy to overcome the obstacles. With polyethylene glycol (PEG) first in
      order, a variety of polymers have been developed to shield the surface of
      therapeutic Ad vectors and well accomplished to extend circulation time in blood
      and reduce liver toxicity. However, although polymer-coated Ads can successfully
      evacuate from a series of guarding systems in vivo and locate within tumors by
      enhanced permeability and retention (EPR) effect, the possibility to entering
      into the target cell is few and far between. To endow targeting moiety to polymer
      coated Ad vectors, a diversity of ligands such as tumor-homing peptides, growth
      factors or antibodies, have been introduced with avoiding unwanted transduction
      and enhancing therapeutic efficacy. Here, we will describe and classify the
      characteristics of the published polymers with respect to Ad vectors.
      Furthermore, we will also compare the properties of variable targeting ligands,
      which are being utilized for addressing polymer-coated Ad vectors actively.

PMID- 22142775
TI  - Diet-dependent net endogenous acid load of vegan diets in relation to food groups
      and bone health-related nutrients: results from the German Vegan Study.
AB  - BACKGROUND/AIMS: Dietary composition has been shown to affect acid-base
      homeostasis and bone health in humans. We investigated the potential renal acid
      load (PRAL) and the estimated diet-dependent net acid load (net endogenous acid
      production, NEAP) in adult vegans and evaluated the relationships between NEAP,
      food groups and intake of bone health-related nutrients. METHODS: The German
      Vegan Study (GVS) is a cross-sectional study. Data from healthy men (n = 67) and
      women (n = 87), aged 21-75 years, who fulfilled the study criteria (vegan diet
      for >=1 year prior to study start; age >=18 years, and no pregnancy/childbirth
      during the last 12 months) were included in the analysis. NEAP values were
      calculated from diet composition using two models: one based on the
      protein/potassium quotient and another taking into account an anthropometry-based
      loss of urinary organic anions. RESULTS: Mean daily intakes of phosphorus,
      potassium, sodium, magnesium and vitamin C were above, and vitamin D and calcium
      below Dietary Reference Intake (DRI). Regardless of the model used, the diet in
      the GVS was characterized by a nearly neutral NEAP. A strong correlation was
      observed between the NEAP values of the two models (r(s) = 0.873, p < 0.001).
      Only the consumption of fruits decreased constantly across the increasing
      quartiles of NEAP. CONCLUSIONS: It can be hypothesized that vegan diets do not
      affect acid-base homeostasis. With respect to bone health, the significance of
      this finding needs further investigation.

PMID- 22142776
TI  - Identifying a high stroke risk subgroup in individuals with heart failure.
AB  - BACKGROUND: Heart failure (HF) is associated with an overall stroke rate that is
      too low to justify anticoagulation in all patients. This study was conducted to
      determine if vascular risk factors can identify a subgroup of individuals with
      heart failure with a stroke rate high enough to warrant anticoagulation. METHODS:
      The REGARDS study is a population-based cohort of US adults aged >=45 years.
      Participants are contacted every 6 months by telephone for self- or proxy
      reported stroke and medical records are retrieved and adjudicated by physicians.
      Participants were characterized into 3 groups: HF without atrial fibrillation
      (AF), AF with or without HF, and neither HF nor AF. Cardiovascular risk factors
      at baseline were compared between participants with and without incident stroke
      in HF and AF. Stroke incidence was assessed in risk factor subgroups in HF
      participants. RESULTS: Of the 30,239 participants, those with missing/anomalous
      data were excluded. Of the remaining 28,832, 1360 (5%) had HF without AF, 2528
      (9%) had AF, and 24,944 (86%) had neither. Previous stroke/transient ischemic
      attack (TIA; P = .0004), diabetes mellitus (DM; P = .03), and higher systolic
      blood pressure (P = .046) were associated with increased stroke risk in
      participants with HF without AF. In participants with HF without AF, stroke
      incidence was highest in those with previous stroke/TIA and DM (2.4 [1.1, 4.0]
      per 100 person-years). CONCLUSIONS: The combination of previous stroke/TIA and DM
      increases the incidence of stroke in participants with HF without AF. No analyzed
      subgroup had a stroke rate high enough to make it likely that the benefits of
      warfarin would outweigh the risks.

PMID- 22142777
TI  - Cerebral infarcts associated with adenomyosis among middle-aged women.
AB  - Cerebral infarcts associated with hypercoagulability in malignant tumors have
      been well recognized. However, reports on cerebral infarcts in patients with a
      benign gynecologic tumor, such as adenomyosis, are extremely limited. We report
      the cases of 4 patients with adenomyosis and cerebral infarcts, all without
      obvious evidence of conventional causes of cerebral infarcts. Brain magnetic
      resonance imaging revealed multiple cerebral infarcts in both cortical and
      subcortical areas in all the patients and in different arterial territories in 3
      patients. Two patients also had systemic embolism in the fingers or kidneys. One
      patient had thrombi in the brachiocephalic trunk and left subclavian artery. The
      levels of coagulation markers were elevated in the acute phase of cerebral
      infarcts. Although cerebral infarcts might be uncommon in adenomyosis patients,
      these patients might be potentially at risk of developing cerebral infarcts
      associated with hypercoagulability related to increased mucinous tumor marker
      levels, menstruation-related coagulopathy, or increased tissue factor expression
      levels. Additional study is required to determine the mechanism underlying the
      development of cerebral infarcts in adenomyosis; however, physicians need to pay
      particular attention to those who have hypercoagulability with adenomyosis among
      middle-aged women.

PMID- 22142778
TI  - Giant serpentine aneurysm of the distal anterior cerebral artery.
AB  - We report a case of a 38-year-old man with a giant serpentine aneurysm arising
      from the distal anterior cerebral artery. This aneurysm grew from a fusiform
      aneurysm to a huge aneurysm within 5 months before manifesting as a mass lesion.
      The aneurysm was largely filled with thrombus, and 4 distal branches arose from
      the aneurysm dome. Selective balloon test occlusion of the distal anterior
      cerebral artery using an intravascular technique was performed to confirm the
      tolerance of the brain tissue. The balloon test occlusion elicited adequate
      leptomeningeal collateral circulation and no neurologic symptoms; thus, the
      aneurysm was treated with trapping and resection. The patient had no ischemic
      complications after the surgery and returned to his job 1 month later. No
      ischemia developed in the 2 years after surgery. Selective balloon test occlusion
      of the distal cerebral artery using an intravascular technique can be a very
      useful tool in planning the therapeutic strategy for a complicated distal
      cerebral aneurysm.

PMID- 22142779
TI  - CHADS2- and CHA2DS2VASc scores and embolic risk in left ventricular
      hypertrabeculation/noncompaction.
AB  - BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVHT) is
      associated with stroke or embolism (S/E). The aim of this study was to assess if
      the Congestive heart failure, Hypertension, Age >75 years, Diabetes, and Stroke
      (CHADS2) and CHA2DS2VASc scores are different between LVHT-patients with and
      without stroke/embolism. METHODS: Records of LVHT patients were retrospectively
      screened. For stroke classification, the Trial of Org 10172 in Acute Stroke
      Treatment (TOAST) criteria were applied, for peripheral embolism angiographic
      findings. Baseline data were compared between patients with and without S/E.
      RESULTS: In 26 of 169 patients (15%), stroke (n = 24) or peripheric embolism (n =
      2) had occurred. S/E etiology was either cardioembolic (n = 18), atherosclerotic
      (n = 5), or undetermined (n = 3). S/E occurred before (n = 17) and after (n = 9)
      diagnosis of LVHT/NC. The prevalence of hypertension (62 vs 35%; P < .05),
      CHADS2, and CHA2DS2-VASc scores were higher in patients with than without S/E
      (2.85 vs 1.26 and 3.69 vs 1.93, respectively; P < .001). CONCLUSIONS: S/E in LVHT
      is not always cardioembolic, but may also have an atherosclerotic cause. The
      CHADS2 score may be useful for clinical decision-making about oral
      anticoagulation for the prevention of S/E in LVHT patients.

PMID- 22142780
TI  - Gender difference in stroke case fatality: an integrated study of hospitalization
      and mortality.
AB  - BACKGROUND: Providing regional and state-specific prognosis factors for stroke
      patients has both clinical and public health importance. Results from previous
      studies of sex difference in stroke case fatality have been mixed. The current
      study links stroke hospitalizations to community-based mortality records to
      examine sex difference in stroke case fatality and associated prognosis factors.
      METHODS: Hospital discharge data and death certificate data from January 2005 to
      December 2009 in Nebraska were linked. Multivariable logistic regression was used
      to estimate sex differences in 30-day mortality, and the Cox proportional hazard
      model was used to predict overall survival. RESULTS: A total of 15,806 patients
      were included. Females were more likely to die during the 30 days after stroke
      hospitalization. However, there was no significant difference in overall survival
      in the multivariate analysis that controlled for age, comorbidity, and
      rehabilitation factors. Females were more likely to have comorbidities, such as
      atrial fibrillation, anemia, and heart failure, while males were more likely to
      have chronic kidney disease. In addition, males were more likely to receive
      rehabilitation services after stroke. CONCLUSIONS: Among persons hospitalized
      with a stroke in Nebraska between 2005 and 2009, the crude case fatality rate was
      50% higher in women. However, after accounting for age and other variables,
      adjusted mortality rates were essentially the same for men and women.

PMID- 22142781
TI  - Molecular characterization of the Aspergillus nidulans fbxA encoding an F-box
      protein involved in xylanase induction.
AB  - The filamentous fungus Aspergillus nidulans has been used as a fungal model
      system to study the regulation of xylanase production. These genes are activated
      at transcriptional level by the master regulator the transcriptional factor XlnR
      and repressed by carbon catabolite repression (CCR) mediated by the wide-domain
      repressor CreA. Here, we screened a collection of 42 A. nidulans F-box deletion
      mutants grown either in xylose or xylan as the single carbon source in the
      presence of the glucose analog 2-deoxy-D-glucose, aiming to identify mutants that
      have deregulated xylanase induction. We were able to recognize a null mutant in a
      gene (fbxA) that has decreased xylanase activity and reduced xlnA and xlnD mRNA
      accumulation. The DeltafbxA mutant interacts genetically with creAd-30, creB15,
      and creC27 mutants. FbxA is a novel protein containing a functional F-box domain
      that binds to Skp1 from the SCF-type ligase. Blastp analysis suggested that FbxA
      is a protein exclusive from fungi, without any apparent homologs in higher
      eukaryotes. Our work emphasizes the importance of the ubiquitination in the A.
      nidulans xylanase induction and CCR. The identification of FbxA provides another
      layer of complexity to xylanase induction and CCR phenomena in filamentous fungi.

PMID- 22142783
TI  - Long-term neurological outcome in children with early-onset epilepsy associated
      with tuberous sclerosis.
AB  - In tuberous sclerosis complex, early seizure onset is associated with high risk
      of intractable epilepsy and cognitive/behavioral impairment. We retrospectively
      evaluated the long-term outcome of 44 infants presenting with seizures in the
      first 12 months who received vigabatrin, and were followed up for at least 3.5
      years. At the final evaluation 55% of patients were still having seizures, 80%
      had intellectual disability, and 30% had autism. Sixty-five percent of children
      who had been treated earlier with vigabatrin after seizure onset achieved seizure
      freedom, compared with 24% of subjects who received vigabatrin treatment later
      (P<0.01). Intellectual disability was present in 61% of the children treated
      early (group A) and in 100% of the children treated later (group B). Nine percent
      of group A and 52% of group B had autism (P~0.001). A shorter gap between seizure
      onset and start of treatment could reduce the risk of epileptic encephalopathy,
      minimizing the deleterious effect of seizures, but is not able to completely
      reverse the tuberous sclerosis complex-associated cognitive impairment.

PMID- 22142782
TI  - Arv1 lipid transporter function is conserved between pathogenic and nonpathogenic
      fungi.
AB  - The lipid transporter Arv1 regulates sterol trafficking, and
      glycosylphosphatidylinositol and sphingolipid biosyntheses in Saccharomyces
      cerevisiae. ScArv1 contains an Arv1 homology domain (AHD) that is conserved at
      the amino acid level in the pathogenic fungal species, Candida albicans and
      Candida glabrata. Here we show S. cerevisiae cells lacking Arv1 are highly
      susceptible to antifungal drugs. In the presence of drug, Scarv1 cells are unable
      to induce ERG gene expression, have an altered pleiotrophic drug response, and
      are defective in multi-drug resistance efflux pump expression. All phenotypes are
      remediated by ectopic expression of CaARV1 or CgARV1. The AHDs of these
      pathogenic fungi are required for specific drug tolerance, demonstrating
      conservation of function. In order to understand how Arv1 regulates antifungal
      susceptibility, we examined sterol trafficking. CaARV1/CgARV1 expression
      suppressed the sterol trafficking defect of Scarv1 cells. Finally, we show that
      C. albicansarv1/arv1 cells are avirulent using a BALB/c disseminated mouse model.
      We suggest that overall cell survival in response to antifungal treatment
      requires the lipid transporter function of Arv1.

PMID- 22142784
TI  - Gamma-hydroxybutyrate detoxification by titration and tapering.
AB  - OBJECTIVE: To determine the effectiveness and safety of a new detoxification
      procedure in gamma-hydroxybutyrate (GHB)-dependent patients. GHB is an endogenous
      inhibitory neurotransmitter and anesthetic agent that is being abused as a club
      drug. In many GHB-dependent patients a severe withdrawal syndrome develops that
      does not respond to treatment with high dosages of benzodiazepines and often
      requires an admission to an intensive care unit. METHODS: Based on the knowledge
      of detoxification procedures in opioid and benzodiazepine dependence, we
      developed a titration and tapering procedure. A consecutive series of 23 GHB
      dependent inpatients were transferred from illegal GHB (mostly self-produced) in
      various concentrations to pharmaceutical GHB. They were given initial doses that
      resulted in a balance between sedation and withdrawal symptoms. After this
      titration period, patients were placed on a 1-week taper. RESULTS: We have found
      that after titration the patients experienced a low level of withdrawal symptoms.
      During tapering these symptoms decreased significantly and no patient developed a
      delirium or a psychosis. None of the patients had to be transferred to a medium
      or intensive care unit. CONCLUSIONS: This detoxification procedure proved to be
      safe and convenient in patients with moderate to severe GHB dependence.

PMID- 22142785
TI  - Kirschmann's Fourth Law.
AB  - Kirschmann's Fourth Law states that the magnitude of simultaneous color contrast
      increases with the saturation of the inducing surround, but that the rate of
      increase reduces as saturation increases. Others since Kirschmann have agreed and
      disagreed. Here we show that the form of the relationship between simultaneous
      color contrast and inducer saturation depends on the method of measurement.
      Functions were measured by four methods: (i) asymmetric matching with a black
      surround, (ii) asymmetric matching with a surround metameric to equal energy
      white, (iii) dichoptic matching, and (iv) nulling an induced sinusoidal
      modulation. Results from the asymmetric matching conditions agreed with
      Kirschmann, whereas results from nulling and from dichoptic matching showed a
      more linear increase in simultaneous contrast with the saturation of the inducer.
      We conclude that the method certainly affects the conclusions reached, and that
      there may not be any "fair" way of measuring simultaneous contrast.

PMID- 22142786
TI  - The face viewpoint aftereffect: adapting to full faces, head outlines, and
      features.
AB  - There is strong evidence that higher visual areas in the brain encode face
      viewpoint. The current study aims to shed light on the nature of this
      representation. Using a psychophysical adaptation paradigm based on Fang and He
      (2005), we compared the effects of adapting to full faces, head outline only, and
      internal features only, while testing with full faces in each case (12 subjects).
      We found reliable viewpoint aftereffects in all three conditions. The combined
      magnitude of the aftereffects from the two partial conditions was less than the
      aftereffect from full faces, suggesting a nonlinear combination of internal
      features and head outline. In a second experiment, we found that changing the
      direction of eye gaze did not modulate the viewpoint aftereffect.

PMID- 22142787
TI  - Disability and dignity-enabling home environments.
AB  - In Canada where long-term care is primarily oriented to elderly persons and
      affordable accessible housing is limited, younger disabled adults may be living
      in circumstances that do not meet their health needs and contribute to their
      social exclusion. The purpose of this study was to undertake an ethical analysis
      of what constitute an 'adequate' home environment for adults with significant
      mobility disabilities. An integrated design was used that combined qualitative
      interviews with normative ethical analysis in an iterative process. Twenty
      interviews with 19 participants were conducted in Ontario, Canada with two
      groups: younger adults (ages 18-55) with mobility disabilities and 'decision
      makers' who consisted of policy makers, program administrators and discharge
      planners. Data were analyzed using a critical disability ethics approach and
      processes of reflective equilibrium. Drawing on Nora Jacobson's (Jacobson, 2009)
      taxonomy of dignity and pluralistic approaches to social justice, the concept of
      'social dignity' provides a lens for exploring the adequacy of home environments
      for disabled people. Analyses suggested seven threshold conditions necessary for
      a dignity-enabling home: the ability to form and sustain meaningful
      relationships; access to community and civic life; access to control and
      flexibility of daily activities; access to opportunities for self-expression and
      identity affirmation; access to respectful relationships with attendants; access
      to opportunities to participate in school, work or leisure; access to physical,
      psychological and ontological security. The results have implications for
      housing, health and social care policies, and political reform. Social dignity
      provides a normative ethical grounding for assessing the adequacy of home
      environments. The threshold elements outline specific dignity-enabling conditions
      that are open to further specification or elaboration in different contexts.

PMID- 22142788
TI  - Malaria in India: the center for the study of complex malaria in India.
AB  - Malaria is a major public health problem in India and one which contributes
      significantly to the overall malaria burden in Southeast Asia. The National
      Vector Borne Disease Control Program of India reported ~1.6 million cases and
      ~1100 malaria deaths in 2009. Some experts argue that this is a serious
      underestimation and that the actual number of malaria cases per year is likely
      between 9 and 50 times greater, with an approximate 13-fold underestimation of
      malaria-related mortality. The difficulty in making these estimations is further
      exacerbated by (i) highly variable malaria eco-epidemiological profiles, (ii) the
      transmission and overlap of multiple Plasmodium species and Anopheles vectors,
      (iii) increasing antimalarial drug resistance and insecticide resistance, and
      (iv) the impact of climate change on each of these variables. Simply stated, the
      burden of malaria in India is complex. Here we describe plans for a Center for
      the Study of Complex Malaria in India (CSCMi), one of ten International Centers
      of Excellence in Malaria Research (ICEMRs) located in malarious regions of the
      world recently funded by the National Institute of Allergy and Infectious
      Diseases, National Institutes of Health. The CSCMi is a close partnership between
      Indian and United States scientists, and aims to address major gaps in our
      understanding of the complexity of malaria in India, including changing patterns
      of epidemiology, vector biology and control, drug resistance, and parasite
      genomics. We hope that such a multidisciplinary approach that integrates clinical
      and field studies with laboratory, molecular, and genomic methods will provide a
      powerful combination for malaria control and prevention in India.

PMID- 22142789
TI  - Large-scale determinants of intestinal schistosomiasis and intermediate host
      snail distribution across Africa: does climate matter?
AB  - The geographical ranges of most species, including many infectious disease agents
      and their vectors and intermediate hosts, are assumed to be constrained by
      climatic tolerances, mainly temperature. It has been suggested that global
      warming will cause an expansion of the areas potentially suitable for infectious
      disease transmission. However, the transmission of infectious diseases is
      governed by a myriad of ecological, economic, evolutionary and social factors.
      Hence, a deeper understanding of the total disease system (pathogens, vectors and
      hosts) and its drivers is important for predicting responses to climate change.
      Here, we combine a growing degree day model for Schistosoma mansoni with species
      distribution models for the intermediate host snail (Biomphalaria spp.) to
      investigate large-scale environmental determinants of the distribution of the
      African S. mansoni-Biomphalaria system and potential impacts of climatic changes.
      Snail species distribution models included several combinations of climatic and
      habitat-related predictors; the latter divided into "natural" and "human
      impacted" habitat variables to measure anthropogenic influence. The predictive
      performance of the combined snail-parasite model was evaluated against a
      comprehensive compilation of historical S. mansoni parasitological survey
      records, and then examined for two climate change scenarios of increasing
      severity for 2080. Future projections indicate that while the potential S.
      mansoni transmission area expands, the snail ranges are more likely to contract
      and/or move into cooler areas in the south and east. Importantly, we also note
      that even though climate per se matters, the impact of humans on habitat play a
      crucial role in determining the distribution of the intermediate host snails in
      Africa. Thus, a future contraction in the geographical range size of the
      intermediate host snails caused by climatic changes does not necessarily
      translate into a decrease or zero-sum change in human schistosomiasis prevalence.

PMID- 22142791
TI  - An amperometric biosensor based on laccase immobilized onto MnO2NPs/cMWCNT/PANI
      modified Au electrode.
AB  - A method is described for construction of an amperometric biosensor for detection
      of phenolic compounds based on covalent immobilization of laccase (Lac) onto
      manganese dioxide nanoparticles (MnO(2)NPs) decorated carboxylated multiwalled
      carbon nanotubes (cMWCNTs)/PANI composite electrodeposited onto a gold (Au)
      electrode through N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) and N
      hydroxy succinimide (NHS) chemistry. The modified electrode was characterized by
      scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical
      impedance spectroscopy (EIS). The biosensor showed optimum response at pH 5.5
      (0.1M sodium acetate buffer) and 35 degrees C, when operated at 0.3 V vs.
      Ag/AgCl. Linear range, response time, detection limit were 0.1-10 MUM (lower
      concentration range) and 10-500 MUM (higher concentration range), 4s and 0.04
      MUM, respectively. Biosensor measured total phenolic content in tea leaves
      extract. The enzyme electrode was used 150 times over a period of 5 months.

PMID- 22142792
TI  - Synthesis, characterization and applications of graft copolymer (kappa
      carrageenan-g-vinylsulfonic acid).
AB  - The synthesis of graft copolymer (kappa-carrageenan-g-vinylsulfonic acid) is
      carried out in nitrogen atmosphere using potassium peroxymonosulfate (PMS) and
      malonic acid (MA) as redox system. The effect of reaction variables including the
      concentration of vinylsulfonic acid 1.3*10(-2) to 6.7*10(-2) mol dm(-3), PMS
      4*10(-3) to 20*10(-3) mol dm(-3), MA 1.6*10(-3) to 4.8*10(-3) mol dm(-3),
      sulfuric acid 1*10(-3) to 8*10(-3) mol dm(-3), kappa-carrageenan 0.4-1.8 g dm(-3)
      as well as time duration 60-180 min and temperature 25-45  degrees C has been
      studied. The water swelling capacity of graft copolymer is investigated.
      Flocculation property for both coking and non-coking coals is studied for the
      treatment of coal mine waste water. The graft copolymer has been characterized by
      FTIR and thermogravimetric analysis.

PMID- 22142793
TI  - Characterization of binding mode of imatinib to human alpha1-acid glycoprotein.
AB  - Imatinib (IMT) is a selective tyrosine kinase inhibitor, used in the treatment of
      chronic myeloid leukemia and gastrointestinal stromal tumors. Its strong plasma
      protein binding was found to belong to the F1*S genetic variant of alpha(1)-acid
      glycoprotein (AGP). In this work, comparative AGP binding studies were performed
      with IMT fragment molecules to reveal which parts of the molecule are important
      in the high-affinity interaction provoking specific spectral changes. Molecular
      modeling calculations indicated that IMT docked into the X-ray structure of
      AGP/F1 adopts a bent, compact conformation. This binding mode is similar to those
      found in its complexes with some low-affinity kinases and a quinone reductase,
      being strikingly different from the extended conformation of IMT in its high
      affinity kinase targets.

PMID- 22142790
TI  - Improving malaria control in West Africa: interruption of transmission as a
      paradigm shift.
AB  - With the paradigm shift from the reduction of morbidity and mortality to the
      interruption of transmission, the focus of malaria control broadens from
      symptomatic infections in children <=5 years of age to include asymptomatic
      infections in older children and adults. In addition, as control efforts
      intensify and the number of interventions increases, there will be decreases in
      prevalence, incidence and transmission with additional decreases in morbidity and
      mortality. Expected secondary consequences of these changes include upward shifts
      in the peak ages for infection (parasitemia) and disease, increases in the ages
      for acquisition of antiparasite humoral and cellular immune responses and
      increases in false-negative blood smears and rapid diagnostic tests. Strategies
      to monitor these changes must include: (1) studies of the entire population (that
      are not restricted to children <=5 or <=10 years of age), (2) study sites in both
      cities and rural areas (because of increasing urbanization across sub-Saharan
      Africa) and (3) innovative strategies for surveillance as the prevalence of
      infection decreases and the frequency of false-negative smears and rapid
      diagnostic tests increases.

PMID- 22142794
TI  - Value of a planned compression ultrasonography after an isolated superficial vein
      thrombosis: results from a prospective multicentre study.
AB  - OBJECTIVES: To assess the efficiency of a systematically planned compression
      ultrasonography (SP-CUS) to detect venous thrombotic complications (VTCs) in
      patients with symptomatic isolated superficial vein thrombosis (SVT). DESIGN:
      Post hoc analysis of a prospective, multicentre, cohort study (POST). PATIENTS:
      As many as 537 patients with CUS-confirmed isolated SVT undergoing an SP-CUS 8-15
      days after the initial CUS. OUTCOMES: Asymptomatic VTC (extension or recurrence
      of SVT, deep-vein thrombosis (DVT) of the lower limbs) diagnosed by the SP-CUS
      and symptomatic thromboembolic complications (VTC and pulmonary embolism (PE)) up
      to 3 months. RESULTS: VTC was suspected before or on the day of the SP-CUS in 18
      patients (3.0%). Among the 519 asymptomatic patients (97%) undergoing SP-CUS,
      this revealed asymptomatic VTC in 12 patients (2.3%; 4 DVT, 4 SVT recurrences, 4
      SVT extensions), none of whom subsequently experienced symptomatic thromboembolic
      events up to 3 months. Among the 507 patients with a normal SP-CUS, 29 (5.7%)
      presented symptomatic thromboembolic events during follow-up: 2 PE, 7 DVT, 9 SVT
      recurrences and 11 SVT extensions. CONCLUSIONS: In this study, the SP-CUS
      detected a few asymptomatic VTC, but failed to identify patients at risk of
      thromboembolic events during follow-up. Use of an SP-CUS was therefore neither
      efficient nor cost effective.

PMID- 22142796
TI  - The prevalence of central poststroke pain according to the integrity of the spino
      thalamo-cortical pathway.
AB  - OBJECTIVES: Little is known about the prevalence of central poststroke pain
      (CPSP) according to the integrity of the spino-thalamo-cortical pathway (STP).
      Using diffusion tensor tractography, we investigated the prevalence of CPSP
      according to the integrity of the STP in patients with intracerebral hemorrhage.
      METHODS: We recruited 52 consecutive chronic patients and 10 normal control
      subjects. Patients were classified into two groups according to preservation of
      the integrity of the STP. Each group was divided into two subgroups according to
      the presence of CPSP. RESULTS: The preserved group included 34 patients [CPSP
      subgroup, 16 (47%) patients; non-CPSP subgroup, 18 (53%) patients], and 18
      patients were enrolled into the disrupted group [CPSP subgroup, 3 (17%) patients;
      non-CPSP subgroup, 15 (83%) patients]. The fractional anisotropy and mean
      diffusivity values of the CPSP and non-CPSP subgroups of the preserved group were
      decreased and increased when compared with those of the control group,
      respectively (p < 0.05). CONCLUSIONS: We found that the prevalence of CPSP in
      patients with partial injury of the STP was higher than that of patients with
      complete injury of the STP. Partial injury of the STP appears to be more
      vulnerable to development of CPSP than complete injury of the STP in patients
      with intracerebral hemorrhage.

PMID- 22142797
TI  - The long term risk of myelodysplastic syndromes among anemia patients: a
      population-based study.
AB  - We have utilized the computerized data of a nationwide health plan to elucidate
      several epidemiologic aspects and risk factor of myelodysplastic syndromes (MDS)
      in Israel. The annual incidence rate (IR) of reported MDS was of 3.32 per
      100,000. Among anemic patients aged 40+, the risk of reported MDS was 56.7 per
      100,000. Only 44% of the reported MDS cases had an indication of bone marrow
      examination. In a multivariable model, older age, hemoglobin level <9 g/dl, white
      blood cell count of less than 3500/mm(3), and platelet count of less than
      100*10(9)/L were associated with a significantly higher risk of MDS. The mean lag
      period from the first demonstration of anemia to the final diagnosis of MDS was
      3.5 years. Our study results could be helpful for improving the detection of
      patients with high MDS risk, therapeutic decision-making, and designing
      interventional trials in the future.

PMID- 22142798
TI  - AKT1 induces caspase-mediated cleavage of the CDK inhibitor p27Kip1 during cell
      cycle progression in leukemia cells transformed by FLT3-ITD.
AB  - p27Kip1 cleavage and caspase-3 regulate cell cycle in human myeloma cells and B
      cells, however regulation of p27Kip1 cleavage during the cell cycle is not known.
      In BaF3-FLT3-ITD cells, p27Kip1 undergoes C-terminal cleavage. Inhibition of the
      PI3K/AKT pathway is associated with decreased cleavage of p27Kip1 and G1 phase
      arrest. A caspase-3 inhibitor reduces p27Kip1 cleavage and inhibits cell
      proliferation. Knockdown shRNA against AKT1 reduces cleavage of p27Kip1, inhibits
      caspase-3 activation, and is associated with a delay in cell cycle progression.
      Taken together, these findings indicate that AKT1 induces caspase-mediated
      cleavage of p27Kip1, required for G1-S progression in FLT3-ITD cells.

PMID- 22142799
TI  - Juvenile hormone action through a defined enhancer motif to modulate ecdysteroid
      activation of natural core promoters.
AB  - We have established a model system of hormone action, in an Sf9 cell transfection
      system, using defined enhancer motifs and natural core promoters of metamorphosis
      associated genes. The DR1 enhancer, that is an established DNA binding site for
      the ecdysone receptor/ultraspiracle heterodimer, was necessary for
      transcriptional activation by 20-OH ecdysone. For this activated transcription, a
      natural sequence closely 5' to the TATA box is necessary. Cotreatment with
      juvenile hormone III strongly suppressed the steroid activation of transcription.
      However, in the absence of the sequence located closely 5' to the TATA box,
      cotreatment with juvenile hormone instead increased transcription over that
      occurring due to 20-hydroxy-ecdysone alone. This sensitivity to activation by
      cotreatment with juvenile hormone could be transferred to a related, but
      otherwise unresponsive, hexamerin core promoter simply by transferring to the
      unresponsive promoter the five base transcription start site (ACAGT) from the
      responsive hexamerin gene. These are the first reports that the direction of JH
      action on 20-OH ecdysone-activated transcription can be reversed by removal of a
      sequence at the core promoter, and that modulatory action of juvenile hormone can
      be transferred to a different gene by transferring the transcription start site
      motif.

PMID- 22142800
TI  - Binding properties of pheromone-binding protein 1 from the common cutworm
      Spodoptera litura.
AB  - Pheromone-binding proteins (PBPs) were formerly thought to act as passive
      pheromone carriers. However, recent studies, particularly in Drosophila
      melanogaster, suggest that PBPs are involved in the recognition of
      semiochemicals, thus making ligand-binding studies more meaningful. Previously,
      we cloned three PBPs from Spodoptera litura (Slit), and showed that SlitPBP1 is
      much more abundant than the other two, particularly in male antennae. To
      investigate the ligand specificity of SlitPBP1, we expressed the protein in a
      bacterial system and performed binding experiments with the three components of
      the specific sex pheromones (Z9-14:Ac, Z9,E11-14:Ac and Z9,E12-14:Ac), as well as
      with 26 volatile ligands. The results indicated that SlitPBP1 bound all three sex
      pheromone components with dissociation constants between 0.6 and 1.1 MUM. The
      same protein also bound with comparable affinities several pheromone analogs, but
      not plant volatiles. The presence of a double bond was the most important element
      for a strong binding, while its position and configuration also affected the
      affinity. Finally, the binding of pheromone components is strongly affected by
      pH, showing a critical pH value corresponding to isoelectric point of the
      protein. This suggests that a pH-dependent conformational mechanism might exist
      in SlitPBP1 for pheromone binding and release.

PMID- 22142801
TI  - Molecular characterization and transcriptional regulation of the sodium-dependent
      vitamin C transporter genes (slc23a1 and slc23a2) in a teleost fish, the
      Senegalese sole (Solea senegalensis).
AB  - Vitamin C (ascorbic acid, AA) is an antioxidant that acts as a free radical
      scavenger and cofactor for several important enzymatic reactions, thus being
      important for normal cellular functions, growth and development. Accumulation of
      AA in cells depends on two types of sodium-dependent vitamin C transporters
      (SVCTs), designed as SVCT1 and SVCT2. In human, they are the products of SLC23A1
      and SLC23A2 genes, respectively. In the present work, the molecular cloning of
      the cDNAs corresponding to slc23a1 and slc23a2 in a teleost fish, the Senegalese
      sole (Solea senegalensis Kaup, 1858) is first described. Sequence analysis of the
      predicted polypeptides revealed a conserved topology with those of mammals with
      important motifs involved in structure and function, being also present in svct1
      and svct2. Phylogenetic analyses including a range of vertebrate SVCTs suggest
      that both transporters are the result of an ancient gene duplication event that
      occurred prior to the divergence of tetrapods and teleosts, which took place 450
      million years ago. Expression profiles in juvenile tissues and during larval
      development were analyzed using a real-time PCR approach. In juvenile fish,
      slc23a1 was strongly expressed in intestine, whereas slc23a2 exhibited a
      widespread distribution in tissues. Transcripts of both genes were detected at
      early developmental stages, probably representing mRNAs of maternal origin. A
      possible regulation by their own substrate was detected after first uptakes of AA
      from diet in both genes. During metamorphosis, both slc23a1 and slc23a2 were down
      regulated, the former in a thyroid hormone (TH) dependent way. This pattern
      coincided with a significant reduction in the AA content of larvae during
      metamorphosis. These results are interpreted in a physiological context of
      general reduction in the metabolism of metamorphic larvae. Data presented here
      provide the first step toward a better understanding of the physiological role of
      SVCTs in teleost fish.

PMID- 22142802
TI  - Expression and regulation of miR-1, -133a, -206a, and MRFs by thyroid hormone
      during larval development in Paralichthys olivaceus.
AB  - MiR-1, miR-133a, and miR-206a have been identified as muscle-specific miRNAs.
      They play multiple crucial roles in the regulation of muscle development. Here,
      we show that these miRNAs were differentially expressed during the larval
      development of flounder, and specifically expressed in skeletal muscle and heart
      in adult tissues/organs. The expression levels of these miRNAs were significantly
      changed by thyroid hormone (TH) or thiourea (TU) treatment during metamorphosis
      from 17 dph (days post hatching) to 42 dph. In addition, the expression levels of
      MyoD and Myf5 mRNAs markedly increased at 14 dph (pre-metamorphosis) compared to
      metamorphic stages, and their expression levels are far above the myogenin during
      larval development. Moreover, these MRFs (myogenic regulatory factors) expression
      were directly or indirectly regulated by thyroid hormone or thiourea during
      metamorphosis. All the results suggest that miRNAs and MRFs might be involved in
      signaling pathway of TH or TU-mediated flounder metamorphosis.

PMID- 22142803
TI  - Successful disease-specific induced pluripotent stem cell generation from
      patients with kidney transplantation.
AB  - INTRODUCTION: End-stage renal disease (ESRD) is a major public health problem.
      Although kidney transplantation is a viable therapeutic option, this therapy is
      associated with significant limitations, including a shortage of donor organs.
      Induced pluripotent stem (iPS) cell technology, which allows derivation of
      patient-specific pluripotent stem cells, could provide a possible alternative
      modality for kidney replacement therapy for patients with ESRD. METHODS: The
      feasibility of iPS cell generation from patients with a history of ESRD was
      investigated using lentiviral vectors expressing pluripotency-associated factors.
      RESULTS: In the present article we report, for the first time, generation of iPS
      cells from kidney transplant recipients with a history of autosomal-dominant
      polycystic kidney disease (ADPKD), systemic lupus erythematosus, or Wilms tumor
      and ESRD. Lentiviral transduction of OCT4, SOX2, KLF4 and c-MYC, under feeder
      free conditions, resulted in reprogramming of skin-derived keratinocytes.
      Keratinocyte-derived iPS cells exhibited properties of human embryonic stem
      cells, including morphology, growth properties, expression of pluripotency genes
      and surface markers, spontaneous differentiation and teratoma formation. All iPS
      cell clones from the ADPKD patient retained the conserved W3842X mutation in exon
      41 of the PKD1 gene. CONCLUSIONS: Our results demonstrate successful iPS cell
      generation from patients with a history of ESRD, PKD1 gene mutation, or chronic
      immunosuppression. iPS cells from autosomal kidney diseases, such as ADPKD, would
      provide unique opportunities to study patient-specific disease pathogenesis in
      vitro.

PMID- 22142804
TI  - Effect of selenium supplementation on glutathione peroxidase and catalase
      activities in senescent cultured human fibroblasts.
AB  - AIMS: To investigate the effect of senescence and selenium supplementation on
      glutathione peroxidase (cGPx) and catalase (CAT) activities, and concurrent
      hydrogen peroxide (H(2)O(2)) generation in subcultured human fibroblasts.
      METHODS: cGPx and CAT activities and H(2)O(2) levels were assayed in presenescent
      passage 5 and 10 cells, and in senescent passage 20, 25, 30 and 35 cells cultured
      in routine medium (MEM1) and supplemented media MEM2 and MEM3 containing normal
      and triple human plasma levels of Se, respectively. Senescent cells were
      identified by studying their growth and replication states, and by monitoring
      their activity of key glucose and glycogen degradative enzymes. RESULTS: cGPx
      activity showed moderate increases in senescent cells at passages 20-35
      subcultured in MEM1 or MEM2. This activity underwent highly significant
      progressive increases in the same senescent cells subcultured in MEM3. In
      contrast, CAT activity showed progressive, highly significant increases in
      senescent cells at passages 20-35 regardless of the culture medium type.
      Concurrent H(2)O(2) generation was significantly increased in passage 15-25 cells
      and peaked to higher levels in passage 30 and 35 cells cultured in MEM1 or MEM2.
      These rates, however, were significantly reduced in senescent passage 20-35 cells
      cultured in MEM3. CONCLUSIONS: The highest cGPx activity and coupled lower
      H(2)O(2) generation were achieved in senescent cells cultured in MEM3.

PMID- 22142805
TI  - Inpatient care for septicemia or sepsis: a challenge for patients and hospitals.
AB  - Septicemia and sepsis are serious bloodstream infections that can rapidly become
      life-threatening. They arise from various infections, including those of the
      skin, lungs, abdomen, and urinary tract. Patients with these conditions are often
      treated in a hospital's intensive care unit. Early aggressive treatment increases
      the chance of survival. In 2008, an estimated $14.6 billion was spent on
      hospitalizations for septicemia, and from 1997 through 2008, the inflation
      adjusted aggregate costs for treating patients hospitalized for this condition
      increased on average annually by 11.9%. Despite high treatment expenditures,
      septicemia and sepsis are often fatal. Those who survive severe sepsis are more
      likely to have permanent organ damage, cognitive impairment, and physical
      disability. Septicemia is a leading cause of death. The purpose of this report is
      to describe the most recent trends in care for hospital inpatients with these
      diagnoses.

PMID- 22142806
TI  - A frequency independent approximation and a sliding mode control scheme for a
      system of a micro-cantilever beam.
AB  - In the present article, a sliding mode controller is proposed for a micro
      cantilever beam (MUCB) with fringing and squeezed film damping effects. The
      narrow micro-cantilever beam can move via the application of an external
      electrically induced force. The introduction of the squeezed film parameters
      results in a frequency-dependent nonlinear system. Particular attention, has been
      paid, in order to approximate the frequency dependent MUCB model, with a valid,
      frequency independent one, that would be incorporated in the design of a robust
      sliding mode controller. The suggested control technique enables compact
      realization of a robust controller tolerant in device characteristics'
      variations, nonlinearities and types of inherent instabilities. Robustness of the
      proposed control scheme against disturbances is proved by Lyapunov's second
      method. In addition, bifurcation analysis is carried on the beam's nonlinear
      model, and numerous simulation test cases are presented in order to test the
      suggested modeling and control techniques.

PMID- 22142807
TI  - Letter to authors on publishing in ISA transactions.

PMID- 22142808
TI  - Increased accumulation of extracellular thrombospondin-2 due to low degradation
      activity stimulates type I collagen expression in scleroderma fibroblasts.
AB  - The aim of the present study was to determine the expression and role of
      thrombospondin-2 (TSP-2) in systemic sclerosis (SSc). Both TSP-2 mRNA levels and
      protein synthesis in cell lysates were significantly lower in cultured SSc
      fibroblasts than in normal fibroblasts; however, the TSP-2 protein that
      accumulated in the conditioned medium of SSc fibroblasts was up-regulated,
      compared with that of normal fibroblasts, because of an increase in the half-life
      of the protein. In vivo serum TSP-2 levels were higher in SSc patients than in
      healthy control subjects, and SSc patients with elevated serum TSP-2 levels
      tended to have pitting scars and/or ulcers. TSP-2 knockdown resulted in the down
      regulation of type I collagen expression and the up-regulation of miR-7, one of
      the miRNAs with an inhibitory effect on collagen expression. Expression levels of
      miR-7 were also up-regulated in SSc dermal fibroblasts both in vivo and in vitro.
      Taken together, these findings suggest that the increased extracellular TSP-2
      deposition in SSc fibroblasts may contribute to tissue fibrosis by inducing
      collagen expression. Down-regulation of intracellular TSP-2 synthesis and the
      subsequent miR-7 up-regulation in SSc fibroblasts may be due to a negative
      feedback mechanism that prevents increased extracellular TSP-2 deposition and/or
      tissue fibrosis. Thus, TSP-2 may play an important role in the maintenance of
      fibrosis and angiopathy in patients with SSc.

PMID- 22142810
TI  - Antibodies against muscle-specific kinase impair both presynaptic and
      postsynaptic functions in a murine model of myasthenia gravis.
AB  - Antibodies against acetylcholine receptors (AChRs) cause pathogenicity in
      myasthenia gravis (MG) patients through complement pathway-mediated destruction
      of postsynaptic membranes at neuromuscular junctions (NMJs). However, antibodies
      against muscle-specific kinase (MuSK), which constitute a major subclass of
      antibodies found in MG patients, do not activate the complement pathway. To
      investigate the pathophysiology of MuSK-MG and establish an experimental
      autoimmune MG (EAMG) model, we injected MuSK protein into mice deficient in
      complement component five (C5). MuSK-injected mice simultaneously developed
      severe muscle weakness, accompanied by an electromyographic pattern such as is
      typically observed in MG patients. In addition, we observed morphological and
      functional defects in the NMJs of EAMG mice, demonstrating that complement
      activation is not necessary for the onset of MuSK-MG. Furthermore, MuSK-injected
      mice exhibited acetylcholinesterase (AChE) inhibitor-evoked cholinergic
      hypersensitivity, as is observed in MuSK-MG patients, and a decrease in both AChE
      and the AChE-anchoring protein collagen Q at postsynaptic membranes. These
      findings suggest that MuSK is indispensable for the maintenance of NMJ structure
      and function, and that disruption of MuSK activity by autoantibodies causes MG.
      This mouse model of EAMG could be used to develop appropriate medications for the
      treatment of MuSK-MG in humans.

PMID- 22142809
TI  - Rac1b increases with progressive tau pathology within cholinergic nucleus basalis
      neurons in Alzheimer's disease.
AB  - Cholinergic basal forebrain (CBF) nucleus basalis (NB) neurons display
      neurofibrillary tangles (NFTs) during Alzheimer's disease (AD) progression, yet
      the mechanisms underlying this selective vulnerability are currently unclear.
      Rac1, a member of the Rho family of GTPases, may interact with the proapoptotic
      pan-neurotrophin receptor p75(NTR) to induce neuronal cytoskeletal abnormalities
      in AD NB neurons. Herein, we examined the expression of Rac1b, a constitutively
      active splice variant of Rac1, in NB cholinergic neurons during AD progression.
      CBF tissues harvested from people who died with a clinical diagnosis of no
      cognitive impairment (NCI), mild cognitive impairment, or AD were immunolabeled
      for both p75(NTR) and Rac1b. Rac1b appeared as cytoplasmic diffuse granules,
      loosely aggregated filaments, or compact spheres in p75(NTR)-positive NB neurons.
      Although Rac1b colocalized with tau cytoskeletal markers, the percentage of
      p75(NTR)-immunoreactive neurons expressing Rac1b was significantly increased only
      in AD compared with both mild cognitive impairment and NCI. Furthermore, single
      cell gene expression profiling with custom-designed microarrays showed down
      regulation of caveolin 2, GNB4, and lipase A in AD Rac1b-positive/p75(NTR)
      labeled NB neurons compared with Rac1b-negative/p75(NTR)-positive perikarya in
      NCI. These proteins are involved in Rac1 pathway/cell cycle progression and lipid
      metabolism. These data suggest that Rac1b expression acts as a modulator or
      transducer of various signaling pathways that lead to NFT formation and membrane
      dysfunction in a subgroup of CBF NB neurons in AD.

PMID- 22142811
TI  - Differentiation-promoting culture of competent and noncompetent keratinocytes
      identifies biomarkers for head and neck cancer.
AB  - Aberrant contact-inhibited proliferation and differentiation induction couple
      with tumor severity, albeit with an imprecise association with prognosis.
      Assessment of contact inhibition and differentiation-promoting culture in this
      study of normal and immortalized oral keratinocytes (NOK and SVpgC2a,
      respectively) demonstrated elevated cloning ability and saturation density in the
      immortalized versus normal state, including consistent absence of differentiated
      morphological features. Transcriptomic analysis implicated 48 gene ontology
      categories, 8 molecular networks, and 10 key regulator genes in confluency
      induced differentiation of NOK, all of which remained nonregulated in SVpgC2a.
      The SVpgC2a versus NOK transcriptome enriched 52 gene ontology categories
      altogether, 18 molecular networks, and 39 key regulator genes, several of which
      were associated with epithelial-mesenchymal transition. Assessment of the
      previously described gene sets relative to training data sets of head and neck
      squamous cell carcinoma samples, one including data on tumor differentiation and
      patient outcome and one present in the Human Gene Expression Map, identified four
      genes with association to poor survival (COX7A1, MFAP5, MPDU1, and POLD1). This
      gene set predicted poor outcome in an independent data set of 71 head and neck
      squamous cell carcinomas. The present study defines, for the first time to our
      knowledge, the broad gene spectrum that couples to induction, and loss, of oral
      keratinocyte differentiation. Bioinformatics assessments of the results relative
      to clinical data generated novel differentiation-related tumor biomarkers
      relevant to patient outcome.

PMID- 22142812
TI  - Developmental profiles and thyroid hormone regulation of brain transcripts in
      frogs: a species comparison with emphasis on Physalaemus pustulosus.
AB  - In amphibians, thyroid hormones (THs) are considered key regulators of brain
      remodeling during metamorphosis, while sex steroids (estrogens and androgens)
      control sexual differentiation and gonadal development. However, these two
      endocrine axes can interact during tadpole brain development. Previously, we
      demonstrated that THs affect sex steroid-related gene expression in the
      developing brain of Silurana tropicalis and Rana pipiens; however, the gene
      expression changes differed between species. We chose to study a third anuran
      species, Physalaemus pustulosus, to test new hypotheses about the role of THs in
      the regulation of brain gene expression. We first established developmental
      transcript profiles of TH- and sex steroid-related genes in the brain of P.
      pustulosus. Then, following the same protocols as in our previous studies, we
      investigated triiodothyronine (T3) regulation of brain transcripts in
      premetamorphic P. pustulosus and then compared the results with our previous two
      studies. In the case of TH-related genes, TH receptor beta (trbeta) and
      deiodinase type 3 (dio3), mRNA developmental profiles were similar in the three
      species and with respect to other species in the published literature. However,
      the profiles of TH receptor alpha (tralpha) and deiodinase type 2 (dio2) mRNA
      revealed differences between anuran species. Among the three anurans we have
      studied, the direction of the T3 regulation of TH-related genes was overall
      similar, but the magnitude of gene expression change differed depending on the
      rate of metamorphosis in a given species. For the sex steroid-related genes, each
      species exhibited similar developmental profiles but differed in their response
      to T3. In P. pustulosus, T3 reduced the expression of aromatase (cyp19) while
      increasing mRNA levels of androgen and estrogen receptors. These results are
      similar to previous research in R. pipiens but differ from data for S.
      tropicalis, for which we found an increase in androgen synthesis enzymes but no
      effect on cyp19. Together, we propose that T3 has the potential to induce the
      brain androgen system in anurans. This could be achieved by increasing androgen
      synthesis enzymes (S. tropicalis) or by decreasing estrogen synthesis (due to a
      decrease in cyp19 in P. pustulosus and R. pipiens). In conclusion, we
      demonstrated that mechanisms of hormone interactions differ between anuran
      species, but in all cases T3 appears to affect the balance of sex steroids in the
      brain, stimulating the androgen system. We have shown that the regulation of sex
      steroid-related genes by T3 is more similar among closely related species than
      species with similar reproductive and developmental characteristics.

PMID- 22142813
TI  - Relationship between the absorption of 5-hydroxytryptophan from an integrated
      diet, by means of Griffonia simplicifolia extract, and the effect on satiety in
      overweight females after oral spray administration.
AB  - The management of overweight may include the use of dietary supplements targeted
      to counter the feeling of hunger. A randomized, double-blind, placebo-controlled
      trial has been performed in 20 overweight females. These subjects were randomly
      assigned to supplement their diet with either an extract from Griffonia
      Simplicifolia (10 subjects) or a placebo (10 matched subjects) for 4-weeks, in
      conjunction with a personalised reduced calorie diet. The main aim of this study
      was to evaluate the efficacy, by the assessment of 24-h urinary 5
      hydroxyindoleacetic acid levels (5-HIAA), of 1-month administration of a dietary
      supplement containing 5-hydroxytryptophan (5-HTP) from botanical extracts in
      healthy, overweight females. Secondary endpoints were the assessment of sensation
      of appetite (by Haber score), body composition, and severity of binge eating. The
      supplemented group had a significant increase of 24-h urinary 5-HIAA levels
      (p<0.001), and a decrease in Haber score (p<0.001) while the placebo group did
      not show significant changes. With regard to changes in body composition,
      statistically significant differences between the treatment groups were found for
      the mean change in BMI, suprailiac skinfold thicknesses, arm circumference and
      hip circumference. Other parameters were found to be similar in the treated and
      in the placebo groups. In conclusion, this study shows that the 5
      hydroxytryptophan present in the Griffonia extract, administered via spray to the
      oral cavity, is adequately absorbed, as confirmed by the increase in 24-h urinary
      5-HIAA, and that the supplementation of the diet of overweight women with 5
      hydroxytryptophan increases the feeling of satiety associated with a decrease in
      BMI.

PMID- 22142814
TI  - Carbon dioxide pneumoperitoneum induces systemic oxidative stress: a clinical
      study.
AB  - OBJECTIVE: To investigate the effect of carbon dioxide pneumoperitoneum on
      systemic oxidative stress by using serum oxidative stress markers (ischemia
      modified albumin (IMA), malondialdehyde (MDA), total oxidant status (TOS), total
      antioxidant status (TAS) and oxidative stress index (OSI)) and to compare their
      effectiveness at clinically accepted safe intra-abdominal pressure levels (<12
      mmHg). STUDY DESIGN: A total of 33 consecutive patients who had a unilateral
      ovarian cyst were enrolled for this prospective clinical study. All women
      underwent a laparoscopic ovarian cystectomy procedure. Venous blood was collected
      from patients preoperatively, 10 min after induction of anesthesia and 30 min
      after insufflation. Preoperative, 10(min), and 30(min) serum IMA, MDA, TOS, OSI
      and TAS levels were compared. RESULTS: The mean age was 29.3 +/- 6.4 and the
      range of operation time was 45-80 min. The mean serum IMA levels showed a
      significant increase 30 min later from CO(2) insufflation (p<0.05). Significant
      alterations were not observed in serum MDA, TOS, OSI or TAS levels. CONCLUSIONS:
      Laparoscopic surgery causes systemic ischemia and this ischemic effect can be
      revealed by measuring serum ischemia modified albumin. IMA is more sensitive than
      MDA, TOS, OSI and TAS in early detection of systemic oxidative stress.

PMID- 22142815
TI  - Maternal caffeine intake and its effect on pregnancy outcomes.
AB  - OBJECTIVE: Estimation of the maternal caffeine intake during pregnancy and its
      influence on pregnancy duration, birthweight and Apgar score of the newborn.
      STUDY DESIGN: The research was conducted on pregnant women who gave birth at the
      Clinic of Obstetrics, Gynaecology and Oncology, 2nd Faculty of Medicine, Medical
      University of Warsaw. It covered unifetal pregnancies without diseases (N=509).
      Research data were collected by direct questionnaire supplemented with data from
      patients' records. Statistical analysis employed a multivariate logistic
      regression model and a non-parametric Spearman's rank correlation coefficient.
      RESULTS: 98.4% of pregnant women consume no more than 300 mg of caffeine per day.
      Pregnant women who smoke and older women consume more caffeine than non-smokers
      and younger women [beta 1.95 (95% CI: 1.02-2.88)] and [beta 0.68 (95% CI: 0.05
      1.3)] respectively. There is no association between maternal caffeine intake
      during pregnancy and the risk of premature birth, the birthweight or the Apgar
      score of newborns. CONCLUSION: Caffeine intake of no more than 300 mg per day
      during pregnancy does not affect pregnancy duration and the condition of the
      newborn.

PMID- 22142816
TI  - Targeted detection of 65 kDa heat shock protein gene in endometrial biopsies for
      reliable diagnosis of genital tuberculosis.
AB  - OBJECTIVE: To evaluate the clinical utility of PCR compared with other available
      diagnostic modalities in prompt diagnosis of female genital tuberculosis causing
      infertility. STUDY DESIGN: Prospective case-controlled trial. Premenstrual
      endometrial biopsy specimens were collected from 150 infertile women of
      reproductive age group suspected of having genital tuberculosis. All patients
      underwent diagnostic endoscopy (laparoscopy and hysteroscopy) and the samples
      obtained were subjected to microscopy, culture by the BACTEC 460 TB System,
      histopathology and polymerase chain reaction (PCR) for detection of 165 bp region
      of 65 kDa gene of Mycobacterium tuberculosis. The results were correlated with
      the laparoscopic findings. RESULTS: While the laparoscopy/hysteroscopy findings
      were indicative of tuberculosis in 12.6% of cases, 14.6% of the specimens showed
      evidence of 65 kDa gene of M. tuberculosis and only 3.33%, 1.33% and 0.66% were
      positive by culture, smear and histopathology, respectively. CONCLUSION: Since
      laparoscopy, hysteroscopy other endoscopic procedures are associated with
      operative risks and may cause flaring of infection, and other conventional
      laboratory tests including histopathology have poor sensitivity, PCR-based
      detection of 65 kDa gene of M. tuberculosis in endometrial biopsy specimens could
      be a promising molecular diagnostic technique compared to conventional methods of
      diagnosis.

PMID- 22142817
TI  - Morphological characteristics and co-stimulatory molecule (CD80, CD86, CD40)
      expression in tumor infiltrating dendritic cells in human endometrioid
      adenocarcinoma.
AB  - OBJECTIVE: The purpose of this study was to investigate changes of the antigen
      presenting function of tumor infiltrating dendritic cells (TIDCs) in human
      endometrioid adenocarcinoma. STUDY DESIGN: The TIDCs from 45 cases of
      endometrioid adenocarcinoma were compared with 20 cases of normal human
      endometrial tissue, using transmission electron microscopic examination, and the
      expression of CD80, CD86, and CD40 was analyzed by flow cytometry. RESULTS: In
      comparison with the control group, the ultrastructure of TIDCs in human
      endometrioid adenocarcinoma showed the following differences: numerous TIDCs were
      small in volume and round in shape but some were oval and multi-angular. The
      cytoplasmic processes were obviously decreased in number and stubbed. Round
      primary lysosomes with high electron-dense granules, and secondary lysosomes with
      high or low electron-dense granules were seen frequently in the cytoplasm. TIDCs
      contained much rough endoplasmic reticulum (RER). Vacuoles with flocculent
      electron-dense granules were rare. High electron-dense contents in the granules
      were near one side and the other side was bright. The nucleus became markedly
      small in volume, nephroid or hoofed in shape. The nucleus had little euchromatin
      and lots of heterochromatin under the nuclear membrane. The levels of expression
      of CD80, CD86 and CD40 on TIDCs were low or even nonexistent. The expression
      levels of CD80, CD86 and CD40 on DCs in human normal endometrium were
      significantly higher than those on TIDCs in endometrioid adenocarcinoma.
      CONCLUSION: It is suggested that morphological differences and low expression of
      co-stimulatory molecules on TIDCs in endometrioid adenocarcinoma reflected the
      functional changes of the TIDCs in uptake, processing and presenting antigen,
      which may lead to the occurrence of tumor immune escape.

PMID- 22142818
TI  - Neuropsychological and radiological assessments of two cases with apparent
      idiopathic rapid eye movement sleep behaviour disorder.
AB  - We examined two male patients (64 and 70 years old) with rapid eye movement sleep
      behaviour disorder (RBD) using cognitive tests, myocardial (123)I
      metaiodobenzylguanidine (MIBG) scintigraphy, and dopamine positron emission
      tomography (PET) imaging. One patient had impaired social cognition and decision
      making skills and reduced MIBG reuptake, and dopamine PET imaging indicated
      striatal terminal loss. The other patient had normal social cognition and reduced
      MIBG reuptake, but no abnormalities were detected by dopamine PET imaging. Both
      patients reported constipation. This study supports the hypothesis by Braak et
      al. [Mov Disord 2006;21:2042-2051] that impairment of the amygdala and striatum
      occurs at the same stage as alpha-synucleinopathy, and the findings suggest that
      autonomic dysfunctions such as reduced MIBG reuptake and constipation are the
      earliest symptoms of RBD. Detailed neuropsychological and radiological
      assessments of these 2 cases revealed that idiopathic RBD could develop in
      various clinical situations and include cognitive and autonomic changes. Further
      longitudinal studies with larger sample sizes will help understand the
      neuropsychology and pathophysiology of RBD.

PMID- 22142819
TI  - Molecular cloning and functional analysis of nucleotide-binding oligomerization
      domain 1 (NOD1) in olive flounder, Paralichthys olivaceus.
AB  - The gene encoding nucleotide-binding oligomerization domain 1 (NOD1) was cloned
      from olive flounder (Paralichthys olivaceus) and the role played by NOD1 during
      Edwardsiella tarda infection was evaluated. The complete open reading frame of
      NOD1 was 2820 bp in length, encoding a 939-amino acid polypeptide. The NOD1
      protein contains three conserved domain structures including C-terminal LRRs, a
      central NACHT motif, and an N-terminal CARD domain, which show similarities of 49
      74% to those of other vertebrate counterpart proteins. NOD1 expression was
      observed in all fish tissues examined, and the levels increased in olive flounder
      infected with E. tarda, Streptococcus iniae, or viral hemorrhagic septicemia
      virus (VHSV). When hirame natural embryo (HINAE) cells over-expressing NOD1 were
      infected with E. tarda, bacterial growth was inhibited, and the IL-1beta
      transcript level increased compared to that of the control. These findings imply
      that NOD1 plays an important role in response to E. tarda infection of olive
      flounder.

PMID- 22142820
TI  - The role of Dietary Approaches to Stop Hypertension (DASH) diet food groups in
      blood pressure in type 2 diabetes.
AB  - The role of each Dietary Approaches to Stop Hypertension (DASH) diet component in
      blood pressure (BP) of patients with diabetes is still uncertain. The aim of the
      present study was to evaluate possible associations of the recommended food
      groups of the DASH diet eating plan with BP values in patients with type 2
      diabetes. In the present cross-sectional study, 225 patients with type 2 diabetes
      (age 61.1 (SD 10.4) years; diabetes duration 13.1 (SD 9.1) years; males 48.4 %;
      BMI 28.5 (SD 4.3) kg/m(2); HbA1c 7.1 (SD 1.3) %; systolic BP 136.7 (SD 20.0)
      mmHg; diastolic BP 78.4 (SD 11.8) mmHg) without dietary counselling during the
      previous 6 months had their dietary intake assessed by 3 d weighed-diet records.
      Patients were divided into two groups according to BP tertiles: LOW BP (first
      tertile) and HIGH BP (second plus third tertiles). Multivariate logistic
      regression models demonstrated that the daily intake of 80 g of fruits per 4184
      kJ (1000 kcal) (OR 0.781; 95 % CI 0.617, 0.987; P = 0.039) or 50 g of vegetables
      per 4184 kJ (1000 kcal) (OR 0.781; 95 % CI 0.618, 0.988; P = 0.040) reduced the
      chance of the presence of HIGH mean BP (MBP >= 92 mmHg) by 22 % each, adjusted
      for possible confounders. In conclusion, fruit and vegetables were the food
      groups of the DASH diet associated with reduced BP values in patients with type 2
      diabetes, and their consumption might play a protective role against increased BP
      values.

PMID- 22142821
TI  - Polybrominated diphenyl ethers (PBDEs) in human serum from Southeast China.
AB  - Polybrominated diphenyl ethers (PBDEs) have been used extensively in electrical
      and electronic products, but little is known about the exposure level in the
      electrical appliance factories workers and nearby local residents. In this study,
      we assessed body burdens of PBDEs in 194 Chinese injection workers from
      electrical appliance factories and also measured 205 blood samples from catering
      workers, leather factory workers, umbilical cord and infertile men for
      comparison. Twelve PBDE congeners in serum samples were measured by GC-MS. The
      highest concentration for total PBDEs was found in injection workers, which is
      positively correlated to employment duration. BDE-209 was the most dominant
      congener followed by BDE-47, 28 and 99. We also found the presence of all twelve
      PBDEs in cord blood, suggesting an evidence of fetal exposure. Concentration of
      BDE-47 was particularly higher in serum samples from infertile men in comparison
      with that of catering workers and leather factory workers.

PMID- 22142822
TI  - Toward the prognostic significance and therapeutic potential of HER3 receptor
      tyrosine kinase in human colon cancer.
AB  - PURPOSE: Abnormal accumulation and dysregulation of the epidermal growth factor
      receptor family member HER3 is associated with the development of various human
      cancers including those of the breast, lung, and ovary. We have previously shown
      that in melanoma HER3 is frequently overexpressed and is associated with poor
      prognosis. However, the importance of HER3 in colon cancer and its putative
      prognostic significance is still unknown. EXPERIMENTAL DESIGN: HER3 expression
      was analyzed in primary colon tumors from 110 patients by immunohistochemistry
      and correlated with time of progression. Parallel to this, the influence of HER3
      overexpression on cell proliferation, migration, invasion, and apoptosis was
      investigated in four different colon cancer cell lines including DLD-1, LoVo,
      CaCO2, and T-84. RESULTS: HER3 was detected at high frequency and exclusively at
      the membrane of the primary tumors. Elevated HER3 expression levels may serve as
      a putative prognostic marker because it associates with cell proliferation and
      decreased time to disease progression. High HER3 protein expression as well as
      phosphorylation levels were detected in tested cells. HER3 downregulation by RNA
      interference abrogated cell proliferation, migration, and invasion. In addition,
      suppression of HER3 resulted in a G(2)-M cell-cycle arrest, induced apoptosis,
      and led to morphologic changes in colon cancer cell lines. Furthermore,
      application of a monoclonal antibody specific to the extracellular portion of the
      receptor reduced heregulin-beta1-induced migration and invasion and also induced
      apoptosis in colon cancer cell lines. CONCLUSION: We postulate that HER3 is
      critically involved in colon cancer progression and may serve as a novel target
      for therapeutic intervention.

PMID- 22142823
TI  - Tumor infiltration by T lymphocytes expressing chemokine receptor 7 (CCR7) is
      predictive of favorable outcome in patients with advanced colorectal carcinoma.
AB  - PURPOSE: An efficient adaptive immunity is critical for a longer survival in
      cancer. We investigated the prognostic value of tumor infiltration by CD8(+) T
      cells expressing the chemokine-receptor-7 (T(ccr7)) and the correlation between
      tumor infiltration by T(ccr7) and regulatory CD4(+)FoxP3(+) T cells (T(reg)) in
      76 metastatic colorectal cancer (mCRC) patients enrolled in a phase III trial.
      EXPERIMENTAL DESIGN: T(ccr7) and T(reg) cell infiltration in tumor samples was
      quantified by immunohistochemistry. The correlation among T(ccr7), T(reg) tumor
      infiltration, and patients' outcome was evaluated. RESULTS: High T(ccr7) tumor
      infiltration was predictive of prolonged OS [high vs. low T(ccr7) score: median
      38 months (95% CI: 24.5-51.4) vs. 20 months (95% CI: 11.4-28.5); HR = 0.48 (95%
      CI: 0.24-0.96); P = 0.03] and prolonged progression-free survival [PFS; high vs.
      low T(ccr7) score: median 12 months (95% CI: 7.7-16.2) vs. 7 months (95% CI: 5.2
      8.7); HR = 0.54 (95% CI: 0.28-1.01); P = 0.01] after front-line chemotherapy.
      Regression analysis did not show correlation between T(ccr7) and T(reg)
      infiltration levels. However, the cluster of patients showing concomitant high
      infiltration by both T(ccr7) and T(reg) disclosed a favorable outcome [double
      high vs. double low tumor infiltration score: median OS = 35 months (95% CI: 20.8
      49.1) vs. 17 months (95% CI: 4.6-29.3); HR = 0.32 (95% CI: 0.12-0.87); P = 0.02
      and median PFS = 11 months (95% CI: 9.4-12.5) vs. 5 months (95% CI: 2.2-7.7); HR
      = 0.43 (95% CI: 0.17-1.06); P = 0.01]. CONCLUSIONS: High T(ccr7) tumor
      infiltration score is a favorable prognostic factor for mCRC. Our findings
      underline the relevance of microenvironment-related immunologic events for
      patient outcome.

PMID- 22142824
TI  - New challenges in endpoints for drug development in advanced melanoma.
AB  - During the past 3 decades, the field of clinical research for the treatment of
      advanced melanoma lacked significant advances. Available drugs had low antitumor
      activity and no proven benefit in overall survival. Recently, new drugs developed
      based on an in-depth understanding of the biology of this disease have shown
      significant benefit, with ipilimumab and vemurafenib having recently shown a
      positive impact in overall survival in patients with metastatic melanoma leading
      to approval in this indication by the U.S. Food and Drug Administration. This
      rapid introduction of new active agents is likely to challenge current notions on
      how to develop future agents for the treatment of melanoma. The strong evidence
      of benefit for initial agents that modulate immune regulatory checkpoints or
      target driver oncogenes has spurred great interest in developing other similarly
      acting agents. However, this will pose problems in the choice of endpoints for
      the future definitive clinical trials, and the hurdles for achieving these
      endpoints will be higher given the similar activity for comparator agents or the
      availability of competing agents for salvage therapy. This new reality will
      likely require tailoring registrational clinical trial endpoints to the patient
      benefits shown in early clinical testing. In this perspective article, we
      illustrate the challenges in the choice of endpoints for registrational trials in
      metastatic melanoma and that, with an improved understanding of the agent being
      developed, the design of the registrational programs can be informed by earlier
      mechanistic studies to define the assumptions for definitive clinical testing.

PMID- 22142825
TI  - Methylated RASSF1a is the first specific DNA marker for minimal residual disease
      testing in neuroblastoma.
AB  - PURPOSE: PCR-based detection of minimal residual disease (MRD) in neuroblastoma
      (NB) is presently based on NB-specific transcripts. However, the expression of
      these targets varies between patients and upon treatment, and only PHOX2B is
      truly specific. RASSF1a is methylated (RASSF1a(M)) in NB, and we investigated
      whether it can serve as a specific and stable DNA MRD marker. PATIENTS AND
      METHODS: The RASSF1a(M)-specific quantitative real-time PCR was tested on control
      bone marrow (BM; n = 50), on 71 NB tumors, and on 159 clinical BM samples at
      diagnosis and at follow-up of 77 patients. Results were compared with a panel of
      RNA markers and correlated with prognosis. RESULTS: RASSF1a(M) was present in all
      stage 4 and 4s tumors (n = 50) and in 86% stages 1 to 3 tumors (n = 21). The
      level of methylation in stage 4 NB was correlated with overall survival (P =
      0.02). RASSF1a(M)-PCR was highly specific (only 1 amplification in 50 control
      samples tested in triplicate) and had a similar sensitivity as the RNA-based
      PCRs, as shown on clinical samples. Moreover, RASSF1a(M) enabled accurate
      quantification without need for the original tumor. CONCLUSIONS: RASSF1a(M) is a
      novel, highly specific DNA marker for MRD detection in NB, equal to PHOX2B in
      specificity and sensitivity, and better suitable for MRD quantification. We
      propose to include RASSF1a(M) in further prospective MRD studies in NB alongside
      RNA MRD markers. In addition, this assay might also be applicable for detection
      of circulating tumor cells in patients with other cancers withRASSF1a(M) such as
      breast or lung cancer.

PMID- 22142826
TI  - Bexarotene via CBP/p300 induces suppression of NF-kappaB-dependent cell growth
      and invasion in thyroid cancer.
AB  - PURPOSE: Retinoic acid (RA) treatment has been used for redifferentiation of
      metastatic thyroid cancer with loss of radioiodine uptake. The aim of this study
      was to improve the understanding of RA resistance and investigate the role of
      bexarotene in thyroid cancer cells. EXPERIMENTAL DESIGN: A model of thyroid
      cancer cell lines with differential response to RA was used to evaluate the
      biological effects of retinoid and rexinoid and to correlate this with RA
      receptor levels. Subsequently, thyroid cancer patients were treated with 13-cis
      RA and bexarotene and response evaluated on radioiodine uptake reinduction on
      posttherapy scan and conventional imaging. RESULTS: In thyroid cancer patients,
      13-cis RA resistance can be bypassed in some tumors by bexarotene. A decreased
      tumor growth without differentiation was observed confirming our in vitro data.
      Indeed, we show that ligands of RARs or RXRs exert different effects in thyroid
      cancer cell lines through either differentiation or inhibition of cell growth and
      invasion. These effects are associated with restoration of RARbeta and RXRgamma
      levels and downregulation of NF-kappaB targets genes. We show that bexarotene
      inhibits the transactivation potential of NF-kappaB in an RXR-dependent manner
      through decreased promoter permissiveness without interfering with NF-kappaB
      nuclear translocation and binding to its responsive elements. Inhibition of
      transcription results from the release of p300 coactivator from NF-kappaB target
      gene promoters and subsequent histone deacetylation. CONCLUSION: This study
      highlights dual mechanisms by which retinoids and rexinoids may target cell
      tumorigenicity, not only via RARs and RXRs, as expected, but also via NF-kappaB
      pathway.

PMID- 22142827
TI  - A genome-wide association study of overall survival in pancreatic cancer patients
      treated with gemcitabine in CALGB 80303.
AB  - BACKGROUND AND AIMS: Cancer and Leukemia Group B 80303 was a randomized, phase
      III study in patients with advanced pancreatic cancer treated with gemcitabine
      plus either bevacizumab or placebo. We prospectively collected germline DNA and
      conducted a genome-wide association study (GWAS) using overall survival (OS) as
      the endpoint. EXPERIMENTAL DESIGN: DNA from 351 patients was genotyped for more
      than 550,000 single-nucleotide polymorphisms (SNP). Associations between OS and
      SNPs were investigated using the log-linear 2-way multiplicative Cox proportional
      hazards model. The subset of 294 genetically European patients was used for the
      primary analysis. RESULTS: A nonsynonymous SNP in interleukin (IL)17F (rs763780,
      H161R) and an intronic SNP in strong linkage disequilibrium (rs7771466) were
      associated with OS using genome-wide criteria (P <= 10(-7)). Median OS was
      significantly shorter (P = 2.61 * 10(-8)) for the rs763780 heterozygotes [3.1
      months; 95% confidence interval (CI), 2.3-4.3] than for the patients without this
      variant (6.8 months; 95% CI, 5.8-7.3). After adjustment by stratification
      factors, the P value for the association was 9.51 * 10(-7). CONCLUSIONS: The
      variant 161R form of IL-17F is a natural antagonist of the antiangiogenic effects
      of wild-type 161H IL-17F, and angiogenesis may play an important role in the
      metastatic spread of pancreatic cancer. In this preliminary study, we hypothesize
      that the angiogenetic potential of pancreatic cancers in patients with variant IL
      17F is higher than that of tumors in patients with wild-type IL-17F, conferring
      worse prognosis. This exploratory GWAS may provide the foundation for testing the
      biology and clinical effects of novel genes and their heritable variants through
      mechanistic and confirmatory studies in pancreatic cancer.

PMID- 22142828
TI  - Stem cell pathways contribute to clinical chemoresistance in ovarian cancer.
AB  - PURPOSE: Within heterogeneous tumors, subpopulations often labeled cancer stem
      cells (CSC) have been identified that have enhanced tumorigenicity and
      chemoresistance in ex vivo models. However, whether these populations are more
      capable of surviving chemotherapy in de novo tumors is unknown. EXPERIMENTAL
      DESIGN: We examined 45 matched primary/recurrent tumor pairs of high-grade
      ovarian adenocarcinomas for expression of CSC markers ALDH1A1, CD44, and CD133
      using immunohistochemistry. Tumors collected immediately after completion of
      primary therapy were then laser capture microdissected and subjected to a
      quantitative PCR array examining stem cell biology pathways (Hedgehog, Notch, TGF
      beta, and Wnt). Select genes of interest were validated as important targets
      using siRNA-mediated downregulation. RESULTS: Primary samples were composed of
      low densities of ALDH1A1, CD44, and CD133. Tumors collected immediately after
      primary therapy were more densely composed of each marker, whereas samples
      collected at first recurrence, before initiating secondary therapy, were composed
      of similar percentages of each marker as their primary tumor. In tumors collected
      from recurrent platinum-resistant patients, only CD133 was significantly
      increased. Of stem cell pathway members examined, 14% were significantly
      overexpressed in recurrent compared with matched primary tumors. Knockdown of
      genes of interest, including endoglin/CD105 and the hedgehog mediators Gli1 and
      Gli2, led to decreased ovarian cancer cell viability, with Gli2 showing a novel
      contribution to cisplatin resistance. CONCLUSIONS: These data indicate that
      ovarian tumors are enriched with CSCs and stem cell pathway mediators, especially
      at the completion of primary therapy. This suggests that stem cell subpopulations
      contribute to tumor chemoresistance and ultimately recurrent disease.

PMID- 22142829
TI  - Oncogene mutation profiling of pediatric solid tumors reveals significant subsets
      of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth
      signaling pathways.
AB  - PURPOSE: In contrast to the numerous broad screens for oncogene mutations in
      adult cancers, few such screens have been conducted in pediatric solid tumors. To
      identify novel mutations and potential therapeutic targets in pediatric cancers,
      we conducted a high-throughput Sequenom-based analysis in large sets of several
      major pediatric solid cancers, including neuroblastoma, Ewing sarcoma,
      rhabdomyosarcoma (RMS), and desmoplastic small round cell tumor (DSRCT).
      EXPERIMENTAL DESIGN: We designed a highly multiplexed Sequenom-based assay to
      interrogate 275 recurrent mutations across 29 genes. Genomic DNA was extracted
      from 192 neuroblastoma, 75 Ewing sarcoma, 89 RMS, and 24 DSRCT samples. All
      mutations were verified by Sanger sequencing. RESULTS: Mutations were identified
      in 13% of neuroblastoma samples, 4% of Ewing sarcoma samples, 21.1% of RMS
      samples, and no DSRCT samples. ALK mutations were present in 10.4% of
      neuroblastoma samples. The remainder of neuroblastoma mutations involved the
      BRAF, RAS, and MAP2K1 genes and were absent in samples harboring ALK mutations.
      Mutations were more common in embryonal RMS (ERMS) samples (28.3%) than alveolar
      RMS (3.5%). In addition to previously identified RAS and FGFR4 mutations, we
      report for the first time PIK3CA and CTNNB1 (beta-catenin) mutations in 5% and
      3.3% of ERMS, respectively. CONCLUSIONS: In ERMS, Ewing sarcoma, and
      neuroblastoma, we identified novel occurrences of several oncogene mutations
      recognized as drivers in other cancers. Overall, neuroblastoma and ERMS contain
      significant subsets of cases with nonoverlapping mutated genes in growth
      signaling pathways. Tumor profiling can identify a subset of pediatric solid
      tumor patients as candidates for kinase inhibitors or RAS-targeted therapies.

PMID- 22142830
TI  - Targeting the mTOR/4E-BP pathway in endometrial cancer.
AB  - Endometrial cancer is the most common gynecologic malignancy. Although it is
      highly treatable in the early stages of disease, therapies for advanced and
      recurrent disease are rarely curative. A molecular and genetic understanding of
      endometrial cancer involves the mTOR signaling pathway, an emerging target for
      treatment of type I disease (the most common presentation). Endometrial cancers
      show a significant reliance on the mTOR pathway for survival, and studies to date
      have revealed a clinical advantage in targeting this pathway. Less well developed
      in the study of endometrial cancer is an understanding of mTOR signaling to its
      major downstream effector, translational control. Given the poor rate of success
      for treatment of late-stage endometrial cancer, increasing attention is being
      directed to the development of new therapeutic approaches, including targeting
      the mTOR pathway. Here, we discuss the potential benefit of targeting mTOR
      combined with existing chemotherapies by monitoring its impact on translational
      regulatory pathways and key translation targets in endometrial cancer. We also
      highlight laboratory and clinical research findings that will provide new avenues
      for future research and clinical development.

PMID- 22142832
TI  - Age- and time interval-specific gamma radiation-induced DNA damage in adult maize
      weevils, Sitophilus zeamais Motschulsky, assessed using comet assays.
AB  - The gamma radiation-induced DNA damage in adult maize weevils, Sitophilus zeamais
      Motschulsky (Coleoptera: Curculionidae), was assessed using single-cell
      electrophoresis (comet assay). Analysis of DNA damage following 0.5 and 1.0 kGy
      of gamma radiation was performed using cells from 1- and 15-day-old adults. Gamma
      irradiated adults from both age groups showed typical DNA fragmentation, whereas
      cells from non-irradiated adults showed more intact DNA than young S. zeamais.
      Investigations using the comet assay showed that tail length, % tail DNA and %
      DNA damage all increased in adults of both age groups when compared to the
      control insects. A maximum comet length of 227.33 MUm was recorded for 15-day-old
      adults at 24h after irradiation with 1.0 kGy and a minimum of 50.12 MUm for 1-day
      old adults at 0 h after irradiation with 0.5 kGy. The percentage of DNA damage
      increased up to 57.31% and 68.15% for 1- and 15-day-old adults, respectively, at
      24h after irradiation with 1.0 kGy, whereas only 8.58% and 12.22% DNA damage were
      observed in the control batches. The results also showed that percentage of DNA
      damage increased at 24h after irradiation compared to that at 0 h. However,
      further studies are needed to confirm these results.

PMID- 22142831
TI  - A multi-sample 94 GHz dissolution dynamic-nuclear-polarization system.
AB  - We describe the design and initial performance results of a multi-sample
      dissolution dynamic-nuclear-polarization (DNP) polarizer based on a Helium
      temperature NMR cryostat for use in a wide-bore NMR magnet with a room
      temperature bore. The system is designed to accommodate up to six samples in a
      revolver-style sample changer that allows changing samples at liquid-Helium
      temperature and at pressures ranging from ambient pressure down to 1 mbar. The
      multi-sample setup is motivated by the desire to do repetitive in vivo
      measurements and to characterize the DNP process by investigating samples of
      different chemical composition. The system can be loaded with up to six samples
      simultaneously to reduce sample loading and unloading. Therefore, series of
      experiments can be carried out faster and more reliably. The DNP probe contains
      an oversized microwave cavity and includes EPR and NMR capabilities for
      monitoring the DNP process. In the solid state, DNP enhancements corresponding to
      ~45% polarization for [1-(13)C]pyruvic acid with a trityl radical have been
      measured. In the initial liquid-state acquisition experiments described here, the
      polarization was found to be ~13%, corresponding to an enhancement factor
      exceeding 16,000 relative to thermal polarization at 9.4 T and ambient
      temperature.

PMID- 22142833
TI  - Effect of melatonin administration on DNA damage and repair responses in
      lymphocytes of rats subchronically exposed to lead.
AB  - Lead exposure induces DNA damage, oxidative stress, and apoptosis, and alters DNA
      repair. We investigated the effects of melatonin co-administered to rats during
      exposure to lead. Three doses of lead acetate (10, 50 and 100mg/kg/day) were
      administered to rats during a 6-week period. Lymphocytes were analyzed. Lead
      exposure decreased glutathione (GSH) levels in blood, and at doses of
      100mg/kg/day and 50mg/kg/day without melatonin, caused high levels of DNA damage,
      induced apoptosis, and altered DNA repair. Melatonin co-treatment did not
      attenuate the effects of lead at 100mg/kg/day, indicating that the effect of
      melatonin on GSH reduction is not sufficient to reduce the genotoxic effects of
      lead at this high dose. After 6 weeks of treatment, decreased weight gain was
      observed in high lead-dose groups (100mg/kg/day), with or without melatonin, and
      in medium-dose groups (50mg/kg/day) with melatonin, compared with the control
      group. The protective action of melatonin against lead toxicity is dependent on
      the dose of lead. Further pharmacological studies are needed to determine whether
      melatonin acts via melatonin membrane receptors on lymphocytes.

PMID- 22142834
TI  - Recombinagenic and mutagenic activities of fluoroquinolones in Drosophila
      melanogaster.
AB  - Fluoroquinolones are widely used in human and in veterinary medicine due to their
      broad-spectrum antibacterial activity. They act by inhibiting type II DNA
      topoisomerases (gyrase and topoisomerase IV). Because of the sequence homology
      between prokaryotic and eukaryotic topoisomerases II, fluoroquinolones can pose a
      hazard to eukaryotic cells. However, published information concerning the
      genotoxic profiles of these drugs in vivo is sparse and inconsistent. We have
      assessed the activities of three fluoroquinolones, ciprofloxacin, enrofloxacin
      and norfloxacin, in the Drosophila melanogaster Somatic Mutation and
      Recombination Test (SMART) and measured their mutagenic and recombinagenic
      potentials. Norfloxacin was non-genotoxic. Ciprofloxacin and enrofloxacin induced
      significant increases in spot frequencies in trans-heterozygous flies. To test
      the roles of somatic recombination and mutation in the observed genotoxicity,
      balancer-heterozygous flies were also analyzed. Ciprofloxacin and enrofloxacin
      were preferential inducers of homologous recombination in proliferative cells, an
      event linked to loss of heterozygosity.

PMID- 22142835
TI  - The association of serum sialic acid with carotid intima-media thickness and
      anthropometric and metabolic parameters in obese children and adolescents.
AB  - BACKGROUND: Sialic acid (SA) has been shown to be a strong predictor of
      cardiovascular mortality in adults. No study in children regarding the
      association of SA with cardiovascular risks exists in the literature. AIM: We
      aimed to investigate the association of SA with anthropometric and metabolic
      parameters and its correlation with metabolic syndrome (MS) and carotid intima
      media thickness (IMT) in obese children. METHODS: A total of 154 obese children
      were included in the study (74 females, 80 males; mean age 11.3 +/- 2.6 years).
      Anthropometric measurements including body fat percentage (BFP) were recorded.
      Fasting lipids and SA levels were measured. The carotid IMT was evaluated with
      ultrasonography. RESULTS: We found a significant correlation between serum total
      SA (TSA) levels and BFP (r = 0.25, p = 0.01 in the whole group; r = 0.43, p =
      0.00 in girls). The group with BFP >=95th percentile had higher TSA levels than
      the group with BFP <95th percentile (p = 0.04). TSA and carotid IMT were weakly
      correlated (r = 0.20, p = 0.01), but the significance was lost after correcting
      for BFP. No correlations were found between TSA and other anthropometric
      measurements. TSA did not correlate with serum fasting glucose, lipids, insulin
      or homeostasis model assessment-insulin resistance. TSA levels were not different
      between children with or without MS. CONCLUSION: Serum TSA levels are
      significantly correlated with BFP in obese children.

PMID- 22142836
TI  - Chronic obstructive pulmonary disease among adults aged 18 and over in the United
      States, 1998-2009.
AB  - Chronic obstructive pulmonary disease (COPD) causes substantial morbidity and
      mortality and may be unrecognized in its early stages. Chronic lower respiratory
      disease (CLRD), which includes both COPD and asthma, was the third leading cause
      of death in the United States in 2008. COPD includes chronic bronchitis and
      emphysema, which both make emptying air from the lungs progressively more
      difficult and can be associated with cough, mucus production, wheezing, and
      breathlessness. Risk factors include primarily cigarette smoking, but also
      exposure to noxious particles or gases, recurrent infection, diet, and genetic
      factors. COPD is often preventable, but there is no cure. Treatment can control
      symptoms and slow disease progression. This report presents trends in COPD
      prevalence, hospitalization, and death rates, and detailed recent estimates for
      population subgroups. Asthma is excluded from this report because it is
      considered a different condition with fully reversible symptoms, although some
      people may have asthma and COPD concurrently.

PMID- 22142838
TI  - Night eating syndrome: a critical review of the literature.
AB  - Clinical psychologists are increasingly called to participate in the treatment of
      obesity, a condition that affects about one-third of adults in the United States.
      A disorder gaining increased recognition for its role in the development and
      maintenance of obesity is Night Eating Syndrome (NES), a relatively novel
      disorder involving morning anorexia, evening hyperphagia and/or nocturnal
      ingestions, and insomnia. NES affects men and women from various racial groups
      and tends to run in families. NES tends to co-occur with mood, anxiety, eating,
      sleep, and substance use disorders and may have implications for weight and
      diabetes management. Relatively little is known about the successful treatment of
      NES. Limited evidence suggests that serotonergic-based pharmacological treatments
      may be beneficial. Psychological interventions, such as psychoeducation, eating
      modification, relaxation strategies, sleep hygiene, cognitive restructuring,
      physical activity, and social support facilitation may also yield beneficial
      results. The purpose of the present paper is to provide an introduction to NES,
      including diagnosis, clinical presentation, assessment, comorbidities, clinical
      implications, and pharmacological and psychological treatment approaches. Areas
      for further study and development are discussed. NES is an emerging area for
      clinical description, evaluation, and intervention.

PMID- 22142837
TI  - The mechanisms underlying overgeneral autobiographical memory: an evaluative
      review of evidence for the CaR-FA-X model.
AB  - Overgeneral autobiographical memory (OGM) has been found to be an important
      cognitive phenomenon with respect to depression and trauma-related
      psychopathology (e.g., posttraumatic stress disorder), and researchers have been
      interested in better understanding the factors that contribute to this proposed
      vulnerability factor. The most prominent model of mechanisms underlying OGM to
      date is Williams et al.'s (2007) CaR-FA-X model. This model proposes that three
      processes influence OGM: capture and rumination, functional avoidance, and
      impaired executive control. The author reviews the current state of support for
      the CaR-FA-X model by evaluating 38 studies that have examined OGM and one or
      more mechanisms of the model. Collectively, these studies reveal robust support
      for associations between OGM and both rumination and impaired executive control.
      OGM also appears to be a cognitive avoidance strategy, and there is evidence that
      avoiding the retrieval of specific memories reduces distress after an aversive
      event, at least in the short term. Important issues that have been left
      unresolved are highlighted, including the nature of the capture phenomenon, the
      role of trauma in functional avoidance, and the developmental nature of
      functional avoidance. Recommendations for future research that will enhance
      understanding of the factors that contribute to OGM are suggested.

PMID- 22142839
TI  - The quantum Zeno effect immunizes the avian compass against the deleterious
      effects of exchange and dipolar interactions.
AB  - Magnetic-sensitive radical-ion-pair reactions are understood to underlie the
      biochemical magnetic compass used by avian species for navigation. Recent
      experiments have provided growing evidence for the radical-ion-pair
      magnetoreception mechanism, while recent theoretical advances have unravelled the
      quantum nature of radical-ion-pair reactions, which were shown to manifest a host
      of quantum-information-science concepts and effects, like quantum measurement,
      quantum jumps and the quantum Zeno effect. We here show that the quantum Zeno
      effect provides for the robustness of the avian compass mechanism, and immunizes
      its magnetic and angular sensitivity against the deleterious and molecule
      specific exchange and dipolar interactions.

PMID- 22142840
TI  - Special issue: Proteolysis 50 years after the discovery of lysosome in honor of
      Christian de Duve.

PMID- 22142841
TI  - Occurrence of secondary fracture around intramedullary nails used for
      trochanteric hip fractures: a systematic review of 13,568 patients.
AB  - INTRODUCTION: A sliding hip screw (SHS) is currently the treatment of choice for
      trochanteric hip fractures, largely due to the low incidence of complications. An
      alternative treatment is the use of intramedullary proximal femoral nails.
      Unfortunately these implants have been associated with a risk of later fracture
      around the implant. The aim of this study was to see if any improvements have
      been made to the current intramedullary nails, to reduce the incidence of
      secondary fracture around the distal tip of the nail. METHODS: We analysed data
      related to 13,568 patients from 89 studies, focusing on the incidence of post
      operative secondary femoral shaft fracture following the use of intramedullary
      nails in the fixation of trochanteric hip fractures. RESULTS: The overall
      reported incidence of secondary fracture around the nail was 1.7%. The incidence
      of fracture has reduced in the 3rd generation Gamma nails when compared to the
      older Gamma nail (1.7% versus 2.6%, p value 0.03). However, the incidence of
      secondary fracture in the 3rd generation Gamma nails is still significantly
      higher than the other brands of short nail (1.7% versus 0.7%, p value 0.0005).
      Long nails had a slight tendency towards a lower risk of fracture although the
      difference was not statistically significant (1.1% versus 1.7%, p value 0.28).
      There was a significantly lower risk of fracture for those nails with a biaxial
      fixation as opposed to uniaxial fixation (0.6% versus 1.9%, p value <0.0001).
      CONCLUSION: Secondary fracture around a proximal femoral nail is one of the most
      significant of fracture healing complications, and this study suggests that
      continuing design changes to this method of fixation has reduced the risk of this
      complication occurring.

PMID- 22142842
TI  - Changes in plasma membrane phospholipids inhibit antibody-mediated lysis.
AB  - A variety of mechanisms have been proposed to explain how tumors evade immune
      destruction. This work has identified one such mechanism that determines
      susceptibility to immune lysis; membrane phospholipid composition altered
      susceptibility to antibody plus complement (Ab+C)-mediated lysis. Effects on
      antibody plus complement-mediated lysis were correlated with levels of major
      histocompatibility complex (MHC) molecules but not inherent resistance to
      complement damage. This cellular mechanism could be a means by which tumor cells
      escape immune detection and destruction.

PMID- 22142843
TI  - Overexpression of phospho mutant forms of transglutaminase 2 downregulates
      epidermal growth factor receptor.
AB  - Simultaneous upregulation of transglutaminase 2 (TG2) and epidermal growth factor
      receptor (EGFR) have been reported in a number of systems. Moreover, TG2 has been
      identified as a downstream target gene for EGF/EGFR. However, it is not known
      whether the relationship between EGFR and TG2 is only one-way or collaborative.
      Using embryonic fibroblasts derived from TG2 null mice (MEF(tg2-/-)), co
      overexpressing native TG2 and EGFR, here we report that TG2 differentially
      regulates EGFR protein in the presence and absence of EGF. In the absence of EGF,
      TG2 facilitates EGFR downregulation whereas in the presence of EGF, TG2 has
      opposite effect on EGFR and facilitates Akt phosphorylation. TG2 mediated ligand
      independent downregulation of EGFR was not observed in MEF(tg2-/-) cells
      overexpressing Ser212Ala phospho mutant form of TG2 suggesting a role of TG2
      phosphorylation in this process. However, similar to native TG2, Ser212Ala-TG2
      mutant was also able to attenuate ligand-dependent down regulation of EGFR in
      MEF(tg2-/-) cells. Interestingly, overexpression of Ser216Ala-TG2 mutant led to
      downregulation of EGFR in MEF(tg2-/-) cells irrespective of the ligand. These
      results were further confirmed in breast cancer cells expressing high levels of
      EGFR. Collectively, data presented here suggests that the relationship between
      EGFR and TG2 is collaborative and phosphorylation of TG2 play a key role in it.
      Phospho mutant forms of TG2 reported in this study may be utilized as a part of a
      novel strategy to downregulate EGFR in cancers with enhanced EGFR signaling.

PMID- 22142844
TI  - Proteasome activity and autophagosome content in liver are reciprocally regulated
      by ethanol treatment.
AB  - The proteasome and autophagy are two major intracellular protein degradation
      pathways and the regulation of each by ethanol metabolism affects cellular
      integrity. Using acute and chronic ethanol feeding to mice in vivo, and precision
      cut rat liver slices (PCLS) ex vivo, we examined whether ethanol treatment
      altered these proteolytic pathways. In acute studies, we gave C57Bl/6 mice either
      ethanol or phosphate-buffered saline (PBS) by gastric intubation and sacrificed
      them 12h later. PCLS were exposed to 0 or 50mM ethanol for 12 and 24h with or
      without 4-methylpyrazole (4MP). In chronic studies we pair-fed control and
      ethanol liquid diets for 4-6 weeks to transgenic mice, expressing the green
      fluorescent protein (GFP) fused to the autophagic marker, microtubule associated
      protein-1 light chain 3 (LC3). Acute ethanol administration elevated
      autophagosomes (AVs), as judged by a 1.5-fold increase in LC3II content over PBS
      gavaged control mice. Hepatic proteasome activity was unaffected by this
      treatment. Compared with controls, ethanol exposure for 12 and 24h to PCLS
      inhibited proteasome activity by 1.5- to 3-fold and simultaneously enhanced AVs
      by 2- to 5-fold. The decrease in proteasome activity and the rise in AVs both
      depended on ethanol oxidation as its inhibition by 4-methylpyrazole (4MP) blocked
      both proteasome inhibition and AV induction. Hepatocytes from mice chronically
      consuming ethanol exhibited a 1.6-fold decline in proteasome activity, and a 4
      fold rise in GFP-LC3 puncta compared with pair-fed control mice. When we exposed
      hepatocytes from these animals to MG262, a proteasome inhibitor, LC3II puncta per
      cell further increased 2- to 5-fold over untreated cells. CONCLUSION: Our
      findings demonstrate that ethanol metabolism generates oxidants, the levels of
      which differentially influence the activities of the proteasome and autophagy.

PMID- 22142845
TI  - Expanding the utility of heptamer-type sgRNA for TRUE gene silencing.
AB  - tRNase Z(L)-utilizing efficacious gene silencing (TRUE gene silencing) is a novel
      technology for suppressing gene expression. TRUE gene silencing is based on a
      unique enzymatic property of mammalian tRNase Z(L), which is that it can cleave
      any target RNA at any desired site by recognizing a pre-tRNA-like or micro-pre
      tRNA-like complex formed between the target RNA and artificial small guide RNA
      (sgRNA). sgRNA is divided into four groups, 5'-half-tRNA, RNA heptamer, hook RNA,
      and ~14-nt linear RNA. One of the final destinations of TRUE gene silencing is to
      generate cancer therapeutic sgRNAs, and from a pharmacological point of view,
      heptamer-type sgRNA appears to be the most appropriate for this purpose. In this
      paper, we present two strategies to expand the utility of heptamer-type sgRNA:
      one is about locked nucleic acid (LNA) modifications of heptamers and the other
      is about usage of double heptamers. We showed that RNA heptamers with LNA
      modifications can work as sgRNA in vitro and in vivo. We also demonstrated that
      two consecutively aligned heptamers can guide target RNA cleavage by human tRNase
      Z(L) as efficiently as a corresponding 14-nt sgRNA in vitro and that a double
      heptamer can work much better than a 14-nt sgRNA in vivo.

PMID- 22142846
TI  - Noncanonical Wnt signaling promotes osteoclast differentiation and is facilitated
      by the human immunodeficiency virus protease inhibitor ritonavir.
AB  - Wnt proteins that signal via the canonical Wnt/beta-catenin pathway directly
      regulate osteoblast differentiation. In contrast, most studies of Wnt-related
      effects on osteoclasts involve indirect changes. While investigating bone mineral
      density loss in the setting of human immunodeficiency virus (HIV) infection and
      its treatment with the protease inhibitor ritonavir (RTV), we observed that RTV
      decreased nuclear localization of beta-catenin, critical to canonical Wnt
      signaling, in primary human and murine osteoclast precursors. This occurred in
      parallel with upregulation of Wnt5a and Wnt5b transcripts. These Wnts typically
      stimulate noncanonical Wnt signaling, and this can antagonize the canonical Wnt
      pathway in many cell types, dependent upon Wnt receptor usage. We now document
      RTV-mediated upregulation of Wnt5a/b protein in osteoclast precursors.
      Recombinant Wnt5b and retrovirus-mediated expression of Wnt5a enhanced osteoclast
      differentiation from human and murine monocytic precursors, processes facilitated
      by RTV. In contrast, canonical Wnt signaling mediated by Wnt3a suppressed
      osteoclastogenesis. Both RTV and Wnt5b inhibited canonical, beta-catenin/T cell
      factor-based Wnt reporter activation in osteoclast precursors. RTV- and Wnt5
      induced osteoclast differentiation were dependent upon the receptor-like tyrosine
      kinase Ryk, suggesting that Ryk may act as a Wnt5a/b receptor in this context.
      This is the first demonstration of a direct role for Wnt signaling pathways and
      Ryk in regulation of osteoclast differentiation, and its modulation by a
      clinically important drug, ritonavir. These studies also reveal a potential role
      for noncanonical Wnt5a/b signaling in acceleration of bone mineral density loss
      in HIV-infected individuals, and illuminate a potential means of influencing such
      processes in disease states that involve enhanced osteoclast activity.

PMID- 22142847
TI  - p38 mitogen-activated protein kinase is a key regulator of 5-phenylselenyl- and 5
      methylselenyl-methyl-2'-deoxyuridine-induced apoptosis in human HL-60 cells.
AB  - Two novel, modified thymidine nucleosides, 5-phenylselenyl-methyl-2'-deoxyuridine
      (PhSe-T) and 5-methylselenyl-methyl-2'-deoxyuridine (MeSe-T), trigger reactive
      oxygen species (ROS) generation and DNA damage and thereby induce caspase
      mediated apoptosis in human HL-60 cells; however, the mechanism leading to
      caspase activation and apoptotic cell death remains unclear. Therefore, we
      investigated the signaling molecules involved in nucleoside derivative-induced
      caspase activation and apoptosis in HL-60 cells. PhSe-T/MeSe-T treatment
      activated two mitogen-activated protein kinases (MAPKs), extracellular-receptor
      kinase (ERK) and p38, and induced the phosphorylation of two downstream targets
      of p38, ATF-2 and MAPKAPK2. In addition, the selective p38 inhibitor SB203580
      suppressed PhSe-T/MeSe-T-induced apoptosis and activation of caspase-3, -9, -8,
      and -2, whereas the jun amino-terminal kinase (JNK) inhibitor SP600125 and the
      ERK inhibitor PD98059 had no effect. SB203580 and an ROS scavenger, tiron,
      inhibited PhSe-T/MeSe-T-induced histone H2AX phosphorylation, which is a DNA
      damage marker. Moreover, tiron inhibited PhSe-T/MeSe-T-induced phosphorylation of
      p38 and enhanced p38 MAP kinase activity, indicating a role for ROS in PhSe
      T/MeSe-T-induced p38 activation. Taken together, our results suggest that PhSe
      T/MeSe-T-induced apoptosis is mediated by the p38 pathway and that p38 serves as
      a link between ROS generation and DNA damage/caspase activation in HL-60 cells.

PMID- 22142848
TI  - Stimulation of the extracellular Ca2+-sensing receptor by denatonium.
AB  - The extracellular Ca(2+)-sensing receptor (CASR) is a promiscuous G-protein
      coupled receptor closely related to the taste receptors T1R1-T1R3. Here we
      analyzed the possibility that apart from being stimulated by external Ca(2+) and
      amino acids, the substances effective as tastants, CASR might serve as a receptor
      for other sapid compounds. CASR was heterologously expressed in HEK-293 cells,
      and their responsivity to a variety of bitter and sweet substances was examined.
      Among them, solely denatonium was found to stimulate Ca(2+) signaling in CASR
      positive HEK-293 cells. Apparently, these Ca(2+) responses were specific, as
      those were inhibited by the CASR antagonist NSP-4123. Altogether, our findings
      indicate that denatonium stimulates CASR by shifting a dose-response curve for
      the principal CASR agonist Ca(2+) to lower concentrations.

PMID- 22142849
TI  - Transgenic over-expression of interleukin-33 in osteoblasts results in decreased
      osteoclastogenesis.
AB  - Interleukin-33 (IL-33) is the most recently identified member of the IL-1 family
      of cytokines, which is primarily known for its proinflammatory functions. We have
      previously reported that IL-33 is expressed by bone-forming osteoblasts, and that
      administration of recombinant IL-33 to bone marrow cultures inhibits their
      differentiation into bone-resorbing osteoclasts. Likewise, while the inhibitory
      effect of IL-33 on osteoclast differentiation was fully abolished in cultures
      lacking the IL-33 receptor ST2, mice lacking ST2 displayed low bone mass caused
      by increased osteoclastogenesis. Although these data suggested a physiological
      role of IL-33 as an inhibitor of bone resorption, direct in vivo evidence
      supporting such a function was still missing. Here we describe the generation and
      bone histomorphometric analysis of a transgenic mouse model (Col1a1-Il33) over
      expressing IL-33 specifically in osteoblasts. While we did not observe
      differences in osteoblast number and bone formation between wildtype and Col1a1
      Il33 mice, the number of osteoclasts was significantly reduced compared to
      wildtype littermates in two independent transgenic lines. Since we did not
      observe quantitative differences in the populations of eosinophils, neutrophils,
      basophils or M2-macrophages from the bone marrow of wildtype and Col1a1-Il33
      mice, our data demonstrate that an inhibition of osteoclastogenesis is one of the
      major physiological functions of IL-33, at least in mice.

PMID- 22142850
TI  - Curcumin regulates airway epithelial cell cytokine responses to the pollutant
      cadmium.
AB  - Cadmium is a toxic metal present in the environment and its inhalation can lead
      to pulmonary disease such as lung cancer and chronic obstructive pulmonary
      disease. These lung diseases are characterized by chronic inflammation. Here we
      show that exposure of human airway epithelial cells to cadmium promotes a
      polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory
      cytokines known to play an important role in pulmonary inflammation. We also
      determined that two distinct pathways controlled secretion of these
      proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL
      6 secretion occurs via an NF-kappaB dependent pathway, whereas IL-8 secretion
      involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant
      curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human
      airway epithelial cells. In conclusion, curcumin could be used to prevent airway
      inflammation due to cadmium inhalation.

PMID- 22142851
TI  - Role of Nanog in the maintenance of marrow stromal stem cells during post natal
      bone regeneration.
AB  - Post natal bone repair elicits a regenerative mechanism that restores the injured
      tissue to its pre-injury cellular composition and structure and is believed to
      recapitulate the embryological processes of bone formation. Prior studies showed
      that Nanog, a central epigenetic regulator associated with the maintenance of
      embryonic stem cells (ESC) was transiently expressed during fracture healing,
      Bais et al. In this study, we show that murine bone marrow stromal cells (MSCs)
      before they are induced to undergo osteogenic differentiation express ~50* the
      background levels of Nanog seen in murine embryonic fibroblasts (MEFs) and the
      W20-17 murine marrow stromal cell line stably expresses Nanog at ~80* the MEF
      levels. Nanog expression in this cell line was inhibited by BMP7 treatment and
      Nanog lentivrial shRNA knockdown induced the expression of the terminal
      osteogenic gene osteocalcin. Lentivrial shRNA knockdown or lentiviral
      overexpression of Nanog in bone MSCs had inverse effects on proliferation, with
      knockdown decreasing and overexpression increasing MSC cell proliferation.
      Surgical marrow ablation of mouse tibia by medullary reaming led to a ~3-fold
      increase in Nanog that preceded osteogenic differentiation during intramembranous
      bone formation. Lentiviral shRNA knockdown of Nanog after surgical ablation led
      to an initial overexpression of osteogenic gene expression with no initial effect
      on bone formation but during subsequent remodeling of the newly formed bone a
      ~50% decrease was seen in the expression of terminal osteogenic gene expression
      and a ~50% loss in trabecular bone mass. This loss of bone mass was accompanied
      by an increased ~2- to 5-fold adipogenic gene expression and observed increase of
      fat cells in the marrow space. In summary these data show that Nanog is expressed
      during surgically induced marrow bone formation and is functionally involved in
      post natal marrow stromal cell maintenance and differentiation.

PMID- 22142853
TI  - The retinal wholemount technique: a window to understanding the brain and
      behaviour.
AB  - The accessibility of the vertebrate retina has provided the opportunity to assess
      various parameters of the visual abilities of a range of species. This thin but
      complex extension of the brain achieves a large proportion of the necessary
      visual processing of an optical image before information is delivered to the
      brain as neural impulses. Studies of the retina as a wholemount or a flattened
      sheet of neural tissue are abundant due to the large amount of information that
      can be analysed, as follows: the level of summation or convergence; the coverage,
      stratification and potential sites of synaptic connections; the spatial resolving
      power; the arrangement of neuronal arrays or mosaics; electrophysiological access
      for the recording of responses to visual stimuli; the spatial arrangement of cell
      dendritic fields; location of retinal 'blind spots' (optic nerve, falciform
      process and pecten); topographic differences in retinal cell sampling; spectral
      filters, and reflective structures. The present study examines all aspects of the
      wholemount technique, including enucleation, fixation, retinal extraction,
      flattening, staining, visualization of labelled cells and stereological mapping
      of cell density. Uniquely, it highlights the crucial technical and often species
      specific differences encountered when examining a range of vertebrate taxa
      (fishes, reptiles, birds and mammals). This broad comparative approach will
      enable future studies to overcome technical difficulties, thus permitting larger
      conceptual questions to be posed regarding the diversity of visual tasks across
      phylogenetic boundaries.

PMID- 22142852
TI  - Early developmental expression of connexin26 in the cochlea contributes to its
      dominate functional role in the cochlear gap junctions.
AB  - Mutations in Gjb2 and Gjb6 genes, coding for connexin26 (Cx26) and Cx30 proteins,
      respectively, are linked to about half of all cases of human autosomal non
      syndromic prelingual deafness. Molecular mechanisms of the hearing impairments,
      however, are unclear. Most cochlear gap junctions (GJs) are co-assembled from
      Cx26 and Cx30 and deletion of either one of them causes deafness. Our previous
      studies have shown that normal hearing is possible in the absence of the Cx30
      gene when Cx26 is over-expressed. To further test unique functional requirements
      for various types of connexins in the hearing, we investigated whether the
      hearing in the conditional Cx26 (cCx26) null mice could be rescued by genetically
      over-expressing Cx30. Multiple lines of control and experimental mouse models
      were used. Auditory brainstem response (ABR) measurements showed normal hearing
      in targeted gene deletion mice when the deleted Cx26 or Cx30 was transgenically
      expressed from integrated bacterial artificial chromosome (BAC), demonstrating
      the effectiveness of the BAC rescue approach. In contrast, severe hearing loss
      was found in cCx26 null mice in which Cx30 was over-expressed. Morphology
      observations were consistent with the ABR data. Cochleae of cCx26 null mice with
      and without the transgenic over-expression of Cx30 both showed the typical
      immature feature of postnatal cochlear development-the closed tunnel of Corti.
      Immunolabeling data and Western blot quantification indicated that the Cx26
      protein expression preceded that of Cx30 during the early postnatal period in the
      cochlea. Null expression of Cx26 may therefore uniquely result in a transient
      period when a total elimination of GJs in functionally-important regions of the
      developing cochlea is possible. We conclude that Cx26 plays an essential role in
      the development of the auditory sensory epithelium and its unique developmental
      functions required for normal hearing is not replaceable by Cx30.

PMID- 22142854
TI  - Lipid changes in the aged brain: effect on synaptic function and neuronal
      survival.
AB  - As the brain ages, cognitive and motor performance decline. This decline is
      thought to be largely due to the accumulation of damaging products from normal
      oxidative metabolism and to the perturbation of general body homeostasis and
      brain-circulation separation. Despite this abundance of insults, the aged brain
      contains few dead neurons, suggesting that aging must be paralleled by triggering
      or enhancing neuronal survival mechanisms. Recent evidence points to the
      contribution of changes in the lipid composition of membranes to both age
      dependent cognitive decline and robust neuronal survival. In this review, we
      describe and discuss the current understanding of the roles of lipids in neuronal
      aging, with special attention to their influence on membrane fusion,
      neurotransmitter receptor dynamics and survival/death signaling pathways.

PMID- 22142855
TI  - Changes in tumor tissue organization in collagen-I sensitize cells to ionizing
      radiation in an ex vivo model of solid mammary tumor growth and local invasion.

PMID- 22142856
TI  - Live by fusion, avoid fission.

PMID- 22142857
TI  - Human T-cell leukemia virus type 1 (HTLV-1) latency: death signaling awakens the
      sleeping retrovirus.

PMID- 22142858
TI  - The dynamics of the Cse4 chaperone Scm3.

PMID- 22142859
TI  - Identifying players in the functional network around pRB.

PMID- 22142860
TI  - Guardian of the genome turns on genes that alert natural killer cells.

PMID- 22142861
TI  - Phosphorylation during mitosis: how many kinases are out there?

PMID- 22142862
TI  - Alu transcription: a rheostat for stem cell aging?

PMID- 22142863
TI  - Acute neuroinflammation and neurogenesis: a role for microglial COX-1.

PMID- 22142864
TI  - p53 and tumor surveillance: killer finds way to recruit assassins.

PMID- 22142865
TI  - TORC1 activation and autophagy inhibition: opposing forces in Rheb-driven
      tumorigenesis.

PMID- 22142866
TI  - Centrin depletion causes cyst formation and other ciliopathy-related phenotypes
      in zebrafish.
AB  - Most bona fide centrosome proteins including centrins, small calcium-binding
      proteins, participate in spindle function during mitosis and play a role in cilia
      assembly in non-cycling cells. Although the basic cellular functions of centrins
      have been studied in lower eukaryotes and vertebrate cells in culture, phenotypes
      associated with centrin depletion in vertebrates in vivo has not been directly
      addressed. To test this, we depleted centrin2 in zebrafish and found that it
      leads to ciliopathy phenotypes including enlarged pronephric tubules and
      pronephric cysts. Consistent with the ciliopathy phenotypes, cilia defects were
      observed in differentiated epithelial cells of ciliated organs such as the
      olfactory bulb and pronephric duct. The organ phenotypes were also accompanied by
      cell cycle deregulation namely mitotic delay resulting from mitotic defects.
      Overall, this work demonstrates that centrin2 depletion causes cilia-related
      disorders in zebrafish. Moreover, given the presence of both cilia and mitotic
      defects in the affected organs, it suggests that cilia disorders may arise from a
      combination of these defects.

PMID- 22142867
TI  - Dietary values of astaxanthin and canthaxanthin in Penaeus monodon in the
      presence and absence of cholesterol supplementation: effect on growth, nutrient
      digestibility and tissue carotenoid composition.
AB  - Penaeus monodon (mean initial wet weight 1.19 (SE 0.01) g) were fed seven diets
      in triplicate: a control diet (D1) without carotenoids; three diets formulated to
      supply 0.1 % astaxanthin alone (D2), 0.2 % astaxanthin alone (D3), and a
      combination of 0.1 % astaxanthin and 1 % cholesterol (D4); three diets with 0.07
      % canthaxanthin alone (D5), 0.13 % canthaxanthin alone (D6), and a combination of
      0.07 % canthaxanthin and 1 % cholesterol (D7). Weight gain (WG, %), specific
      growth rate (SGR, %/d) and survival were chosen as parameters of shrimp growth
      performance. Total antioxidant status (TAS), superoxide dismutase (SOD),
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were chosen
      as indices of shrimp plasma antioxidant capacity. Meanwhile, digestibility,
      retention efficiency and tissue carotenoids were also investigated to determine
      the additive effect of cholesterol on the efficiency of astaxanthin and
      canthaxanthin. After 74 d rearing, WG and SGR of shrimp fed D2-D4 and D7 were
      higher than those of shrimp fed D1 (P < 0.05). Shrimp fed D4 had the highest
      survival. The apparent digestibility coefficients (ADC) of astaxanthin in D2-D4
      were higher than those of canthaxanthin in D5-D7 (P < 0.05). Although ADC of
      astaxanthin were quite high (>98 %) in D2-D4 and no differences were found among
      them (P>0.05), the carotenoid retention efficiencies in the whole body, muscle
      and shell (D2-D3 treatments) were considerably low; however, cholesterol
      supplementation significantly improved the carotenoid retention efficiencies in
      the whole body, muscle and shell (D4 treatment). Accordingly, the addition of
      cholesterol also significantly enhanced the carotenoid contents of tissues.
      Shrimp fed supplemented carotenoid diets (D2-D7) had higher TAS and lower SOD,
      ALT and AST than shrimp fed D1 (P < 0.05). A low dissolved oxygen stress test was
      conducted for 7 d after the rearing trial and shrimp survival was also compared
      among the treatments. The survival of shrimp fed the diets supplemented with
      astaxanthin or canthaxanthin was higher than that of shrimp fed D1 during the
      stress test (P < 0.05). In conclusion, all data suggested that astaxanthin was
      better than canthaxanthin as the dietary carotenoid source in the commercial diet
      of P. monodon, and the supplement of cholesterol could positively enhance the
      efficiency of astaxanthin and canthaxanthin.

PMID- 22142868
TI  - Mitochondrial complex I deficiency of nuclear origin I. Structural genes.
AB  - Complex I (or NADH-ubiquinone oxidoreductase), is by far the largest respiratory
      chain complex with 38 subunits nuclearly encoded and 7 subunits encoded by the
      mitochondrial genome. Its deficiency is the most frequently encountered in
      mitochondrial disorders. Here, we summarize recent data obtained on architecture
      of complex I, and review the pathogenic mutations identified to date in nuclear
      structural complex I genes. The structural NDUFS1, NDUFS2, NDUFV1, and NDUFS4
      genes are mutational hot spot genes for isolated complex I deficiency. The
      majority of the pathogenic mutations are private and the genotype-phenotype
      correlation is inconsistent in the rare recurrent mutations.

PMID- 22142869
TI  - Correlates of perceived effectiveness of the Safe Schools/Healthy Students
      Initiative.
AB  - A three-level growth-curve model was applied to estimate perceived impact growth
      trajectories, using multi-year data from project and school surveys on outcome
      and program implementation collected from 59 sites and approximately 1165
      participating schools in the Safe Schools and Healthy Students Initiative.
      Primary interest is to determine whether and how project-level and school-level
      correlates affect schools' perceptions of the Initiative's effectiveness over
      time when the effects of the pre-grant environmental conditions, grant
      operations, and near-term outcomes are considered. Coordination and service
      integration, comprehensive programs and activities for early childhood
      development, and change in school involvement were found to be significant
      predictors of school-perceived overall impact when the effect of poverty was
      considered. Partnership functioning, perceived importance of school resources,
      and school involvement were found to be significant predictors of school
      perceived impact on substance use prevention when the effect of poverty was
      considered.

PMID- 22142870
TI  - A rare paramedian mesodiencephalic infarction.

PMID- 22142871
TI  - Antiatherogenic effect of antioxidant polyphenols from Phellinus baumii in
      apolipoprotein E-deficient mice.
AB  - AIMS: The present study was carried out to investigate the antiatherosclerotic
      effect of antioxidant polyphenols from Phellinus baumii (PBE) in apolipoprotein E
      deficient (apoE-/-) mice. METHODS AND RESULTS: apoE-/- mice were randomly divided
      into three groups: mice on a normal chow diet comprised the normal group, mice on
      an atherogenic diet plus vehicle were the control group, and mice on an
      atherogenic diet plus PBE (500 mg/kg) comprised the PB500 group. After 8 weeks of
      treatment, the plasma lipids and cytokine levels were measured. Although no
      significant differences were found in cholesterol levels among groups, the
      triglyceride level was significantly decreased in the PBE-treated group compared
      with the control group. Plasma tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-6 levels were reduced by PBE treatment. Real-time PCR analysis of the aorta
      showed that PBE significantly prevented the upregulation of the vascular cell
      adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, TNF-alpha,
      IL-6, and IL-1beta expression. Furthermore, reduced macrophage infiltration,
      lipid accumulation and atherosclerotic lesions were observed in the aortic sinus
      and en face of the whole aorta in PBE-fed apoE-/- mice compared with atherogenic
      diet-fed control mice. CONCLUSIONS: Collectively, the findings of the present
      study suggest that the antiatherosclerotic effect of PBE is probably related to
      the inhibition of adhesion molecule and cytokine expression resulting in
      amelioration of lesion development.

PMID- 22142873
TI  - Death in the United States, 2009.
AB  - Mortality in the United States is best summarized by the age-adjusted death rate-
      a measure that accounts for changes in the age distribution of the population.
      This rate has declined in an almost uninterrupted manner since 1960. The death
      rate is now 45 percent lower than in 1960 (declining from 1,339.2 per 100,000
      standard population in 1960 to 741.0 in 2009). Although age-adjusted mortality
      has declined for all demographic groups over a period of many decades, long
      standing gaps between black and white populations and between male and female
      populations have begun to narrow only since the mid-1990s. Many of the recent
      improvements in death rates and life expectancy for all population groups can be
      attributed to ongoing reductions in death rates from major causes of death, such
      as heart disease, cancer, stroke, and chronic lower respiratory diseases. The
      figures presented in this report are based on preliminary mortality data for
      2009.

PMID- 22142872
TI  - Fifteen weeks of dietary n-3 polyunsaturated fatty acid deprivation increase
      turnover of n-6 docosapentaenoic acid in rat-brain phospholipids.
AB  - Docosapentaenoic acid (DPAn-6, 22:5n-6) is an n-6 polyunsaturated fatty acid
      (PUFA) whose brain concentration can be increased in rodents by dietary n-3 PUFA
      deficiency, which may contribute to their behavioral dysfunction. We used our in
      vivo intravenous infusion method to see if brain DPAn-6 turnover and metabolism
      also were altered with deprivation. We studied male rats that had been fed for 15
      weeks post-weaning an n-3 PUFA adequate diet containing 4.6% alpha-linolenic acid
      (alpha-LNA, 18:3n-3) or a deficient diet (0.2% alpha-LNA), each lacking
      docosahexaenoic acid (22:6n-3) and arachidonic acid (AA, 20:4n-6). [1-(14)C]DPAn
      6 was infused intravenously for 5min in unanesthetized rats, after which the
      brain underwent high-energy microwaving, and then was analyzed. The n-3 PUFA
      deficient compared with adequate diet increased DPAn-6 and decreased DHA
      concentrations in plasma and brain, while minimally changing brain AA
      concentration. Incorporation rates of unesterified DPAn-6 from plasma into
      individual brain phospholipids were increased 5.2-7.7 fold, while turnover rates
      were increased 2.1-4.7 fold. The observations suggest that increased metabolism
      and brain concentrations of DPAn-6 and its metabolites, together with a reduced
      brain DHA concentration, contribute to behavioral and functional abnormalities
      reported with dietary n-3 PUFA deprivation in rodents. (196 words).

PMID- 22142874
TI  - An audit of indications and complications associated with elective hysterectomy
      at a public service hospital in South Africa.
AB  - OBJECTIVE: To assess relationships between clinical indication for hysterectomy
      and postoperative histologic findings, and to audit complications of hysterectomy
      at the gynecologic surgical unit of a public-service hospital in South Africa.
      METHODS: Surgical indications and details, histologic findings, and postoperative
      course were reviewed and analyzed for 335 patients who underwent hysterectomy at
      Groote Schuur Hospital, Cape Town, South Africa, in 2007. RESULTS: Hysterectomy
      was performed abdominally in 265 patients (79.1%) and vaginally in 70 (20.9%)
      patients (5 of these procedures were laparoscopically assisted). The most common
      indication was fibroid-related menorrhagia (23%), followed by abnormal uterine
      bleeding (14.9%). The incidence of intraoperative complications was 6-fold
      greater among patients with malignant disease than among those with a benign
      condition (P=0.001). The incidence of postoperative complications was greater
      following abdominal rather than vaginal surgery, whether traditional or
      laparoscopic (P=0.02). CONCLUSION: Most hysterectomies were carried out
      abdominally rather than vaginally, in part because many patients presented with
      advanced cancer or other condition that warranted this approach. Because of
      resource constraints, patients with benign conditions were more likely to be
      offered surgery if they had a clearly defined condition.

PMID- 22142876
TI  - [The future of family practice care in Germany - good ideas to implement
      regionally].

PMID- 22142875
TI  - Lead concentrations in relation to multiple biomarkers of cardiovascular disease:
      the Normative Aging Study.
AB  - BACKGROUND: Lead exposure has been associated with cardiovascular disease (CVD)
      in animal and human studies. However, the mechanisms of action have not been
      fully elucidated. We therefore examined the relationship between lead and
      multiple biomarkers of CVD. METHODS: Participants were older men from the
      Normative Aging Study without preexisting coronary heart disease, diabetes, or
      active infection at baseline (n = 426). Serum biomarkers included lipid profile
      [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein
      (LDL), and triglycerides] and inflammatory markers [C-reactive protein,
      intercellular adhesion molecule-1, interleukin-6, and tumor necrosis factor
      receptor-2 (TNF-R2)]. We measured lead in blood and in bone by K-shell X-ray
      fluorescence. In this sample, 194 men (44.3%) had two or more repeated measures,
      resulting in 636 observations for analysis. We conducted analyses using mixed
      effects models with random subject intercepts. RESULTS: Lead levels were
      associated with several CVD biomarkers, including levels of TNF-R2 and lipid
      markers. Specifically, in multivariable models, a 50% increase in blood lead
      level was associated with 26% increased odds of high TNF-R2 levels (> 5.52 ng/mL;
      odds ratio = 1.26; 95% confidence interval: 1.09, 1.45). There were positive
      associations of blood lead level with total cholesterol and HDL levels, and these
      associations were more evident when modeled as continuous outcomes than when
      categorized using clinically relevant cut points. In addition, longitudinal
      analyses indicated a significant increase in TNF-R2 levels over time to be
      associated with high blood lead level at the preceding visit. CONCLUSIONS: Blood
      lead level may be related with CVD in healthy older men through its association
      with TNF-R2 levels. In addition, the magnitude of the association of blood lead
      level with TNF-R2 level increased with age in the study population.

PMID- 22142877
TI  - [The quality of chronic care in Germany].
AB  - Over the last ten years changes in the legal framework of the German health care
      system have promoted the development of new health service models to improve
      chronic care. Recent innovations include the nation-wide introduction of disease
      management programmes (DMPs), integrated care contracts, community nurse
      programmes, the introduction of General Practitioner (GP)-centred care contracts,
      and new opportunities to offer interdisciplinary outpatient care in polyclinics.
      The aim of this article is to describe the recent developments regarding both the
      implementation of new health care models by statutory health insurance companies
      and their evaluation. As part of a European project on the development and
      validation of disease management evaluation methods (DISMEVAL), we carried out a
      selective literature search to identify relevant models and evaluation studies.
      However, on the basis of the currently available evaluation and study results it
      is difficult to judge whether these developments have actually led to an
      improvement in the quality of chronic care in Germany. Only for DMPs, evaluation
      is legally mandatory; its methods are inappropriate, though, for studying the
      effectiveness of DMPs. Further study results on the effectiveness of DMPs mostly
      focus on the DMP Diabetes mellitus type II and show consistent improvements
      regarding process parameters such as regular routine examinations, adherence to
      treatment guidelines, and quality of life. More research will be needed to
      determine whether DMPs can also help reduce the incidence of secondary disease
      and mortality in the long term.

PMID- 22142878
TI  - [Primary care practices in Germany: a model for the future].
AB  - In its 2009 report the Federal Advisory Council on the Assessment of Developments
      in the Health Care System developed a model of Primary Care Practices for future
      general practice-based primary care. This article presents the theoretical
      background of the model. Primary care practices are seen as developed
      organisations requiring changes at all system levels (interaction, organisation,
      and health system) to ensure sustainability of primary care functions in the
      future. Developments of the elements comprising the health care system may be
      compared to the developments and proposals observed in other countries. In
      Germany, however, the pace of these developments is relatively slow.

PMID- 22142880
TI  - Commentary: preparing primary care for the future - perspectives from the
      Netherlands, England, USA and lessons for Germany.
AB  - BACKGROUND: Like the Netherlands, England, and the USA, Germany is facing
      challenges posed by globalisation, medical and technological progress, and
      demographic change. Strategies to meet these challenges and practice models in
      these countries vary because they depend on the organisation and funding of the
      health care system and the traditional role of primary care. However, some of the
      approaches from other countries and health care systems may be transferable to
      the German situation. METHOD: We describe the background and the main challenges
      for primary care in Germany. Subsequently, we review the strategies pursued to
      prepare primary care for the future in the Netherlands, England, and the USA and
      analyse their applicability for Germany. RESULTS: All countries reviewed struggle
      with the improvement of cooperation and integration of care for patients with
      chronic illness. Proposed changes concern the organisation and funding of primary
      care, including cooperation in multidisciplinary teams within larger
      organisations such as virtual provider networks, GP-led health centres, or
      polyclinics which focus on the management of the patient population they are
      accountable for. This can be aided by national standards of care, care pathways,
      and guidelines. An appropriate funding model should provide incentives for
      population management which includes the whole team, e.g. through a mixture of
      capitation, fee-for-service, and pay-for-performance. CONCLUSION: The strategies
      pursued in other countries suggest how primary care in Germany could be
      restructured and improved to prepare for future challenges. However, in addition
      to considerable changes in organisation, funding, and incentives, educational,
      cultural, and other conditions need to be taken into account as well, especially
      in the case of forming multidisciplinary care teams. Improvement collaboratives
      and a national programme of practice coaches could be a way to prepare GP
      practices for and help them implement such major changes.

PMID- 22142879
TI  - Preparing primary care for the future - perspectives from the Netherlands,
      England, and USA.
AB  - BACKGROUND: All modern healthcare systems need to respond to the common
      challenges posed by an aging population combined with a growing number of
      patients with (complex) chronic conditions and rising patient expectations.
      Countries with 'stronger' primary care systems (e.g. the Netherlands and England)
      seem to be better prepared to address these challenges than countries with
      'weaker' primary care (e.g. USA). The role of primary care in a health care
      system is strongly related to its organisation and funding, thus determining the
      starting point and the possibilities for change. METHOD: We selected the
      Netherlands, England, and USA as examples for the diversity of approaches to
      organise and finance health care. We analysed the main problems for primary care
      and reviewed strategies and practice models used to meet the challenges described
      above. RESULTS: The Netherlands aim to strengthen prevention for chronic
      diseases, while England strives to improve the management of patients with
      multimorbidity, prevent hospital admissions to contain costs, and to satisfy the
      increased demand of patients for access to primary care. Both countries seek to
      reorganise care around the patient and place their needs at the centre. The USA
      has to provide sufficient workforce, organisation, and funding for primary care
      to ensure better access, prevention, and provision of chronic care for its
      population. Strategies to improve (trans-sectoral) cooperation and care
      coordination, a main issue in all three countries, include the implementation of
      standards of care and bundled payments for chronic diseases in the Netherlands,
      GP commissioning, federated and group practice models in England, and the
      introduction of the Patient-Centred Medical Home and accountable care
      organisations in the USA. CONCLUSION: Organisation and financing of health care
      differ widely in the three countries. However, the necessity to improve
      coordination and integration of chronic disease care remains a common and core
      challenge.

PMID- 22142881
TI  - [Implementing population-based integrated care for a region: a work-in-progress
      report on the project "Gesundes Kinzigtal"].
AB  - The regional integrated care model "Gesundes Kinzigtal" pursues the idea of
      integrated health care with special focus on increasing the health gain of the
      served population. Physicians (general practitioners) and psychotherapists,
      physiotherapists, hospitals, nursing services, non-profit associations, fitness
      centers, and health insurance companies work closely together with a regional
      management company and its programs on prevention and care coordination and
      enhancement. The 10 year-project is run by a company that was founded by the
      physician network "MQNK" and "OptiMedis AG", a corporation with public health
      background specialising in integrated health care. The aim of this project is to
      enhance prevention and quality of health care for a whole region in a sustainable
      way, and to decrease costs of care. The article describes the special funding
      model of the project, the engagement of patients, and the different health and
      prevention programmes. The programmes and projects are developed, implemented,
      and evaluated by multidisciplinary teams.

PMID- 22142882
TI  - [Problems of evaluating regional integrated care using the example of "Gesundes
      Kinzigtal Integrated Care"].
AB  - "Gesundes Kinzigtal Integrated Care" (GKIC) is one of the few population-based
      integrated care systems in Germany. The external evaluation of GKIC has a modular
      design and is coordinated by the Department of Medical Sociology of Freiburg
      University. In this article we will outline the different evaluation modules and
      address typical problems arising in the evaluation of regional integrated health
      care systems. One of these problems is the small size of the intervention
      population in a recently established pilot care system which makes the use of
      epidemiologic measures (such as incidence figures) difficult. Total population
      surveys could alleviate this problem, but when the same intervention population
      is questioned repeatedly for different evaluation modules, the danger of 'over
      surveying' arises. This may lead to decreasing participation in further studies.
      These problems may be managed by using short survey instruments, by conducting
      surveys successively (not simultaneously) using time shifts, and by analysing
      claims data from health insurers. Another problem in the evaluation of comparably
      small systems of care is how to attribute outcomes (effects) to certain health
      promotion or disease management programmes: Since participants usually take part
      in more than one programme, the intervention effect is contaminated by multiple
      programme effects. These will have to be adjusted for in the final evaluation of
      the data. Finally, randomised controlled study (RCT) designs frequently cannot be
      used in the evaluation of a region-wide pilot intervention, so the evidence
      generated by such a (non-randomised) study is weaker than the evidence generated
      by an RCT.

PMID- 22142883
TI  - [State-wide follow-up of extremely preterm infants: a model of cross-sectoral
      quality analysis].
AB  - A long-term outcome project for the special high-risk group of extremely preterm
      (ELBW) infants has been established in the federal state of Lower Saxony, which
      is unique in Germany. All departments of neonatology and all divisions of
      paediatric neurology are participating. Since October 2004 children who were born
      at <28 weeks gestation are examined using a standardised concept at defined
      follow-up intervals (at the age of 6 months, 2, 5 and 10 years). The aim is to
      achieve a cross-sectoral improvement of quality in healthcare on the basis of
      neurodevelopmental outcome parameters (the right therapy for the right child, at
      the right time). So far 739 extremely preterm infants (81% of the survivors) were
      examined at the age of six months, 513 ELBW infants (74% of the survivors) at the
      age of two years, and 99 children (59% of the survivors) at the age of five
      years. The comparison of the follow-up intervals has demonstrated an increase of
      children with minor and major impairment, which indicates the importance of the
      long-term scheme. At the age of five years 27% of the children exhibit normal
      development, 49% minor impairment and 24% major impairment. Many ELBW infants
      need therapy. The model of the project can be transferred to other federal states
      or regions and other high-risk groups.

PMID- 22142884
TI  - [Introductory overview article: internationalization of the health care
      industry].

PMID- 22142885
TI  - [The user oriented hospital - chances and challenges for the healthcare
      industry].
AB  - Hardly any other part of the healthcare sector is under such a pressure to change
      as the hospital sector. Hospitals are high-performers in coping with complex
      changes in modernising patient care, process design, quality, cost-effectiveness
      and service orientation. But, what really makes value to the patient? Currently,
      this question is raised with new seriousness. Those hospitals which consequently
      align their portfolio to value based and 'patient driven' healthcare delivery
      will succeed by both quality and cost-effectiveness. We receive such messages
      from the USA. In Germany there are on-going and admonishing pleas since the end
      of the 1990s not to lose sight of the patients' needs while designing new
      concepts for healthcare delivery. Future challenges imply not only the
      renaissance of patient centred care, but also demand for a comprehensive user
      orientation as a key factor to successful hospital modernisation. This is
      particularly true of concepts of structured, integrated and regional healthcare
      delivery. But a consequent alignment of healthcare with value for patients
      clearly exceeds the focus on integrating hospital and outpatient care. In
      designing new services of coordinated regional healthcare, hospitals gain
      strategic options for a single-source healthcare delivery. In terms of business
      development, user orientation does not only yield important impulses for stronger
      patient centred care, but also opens up chances for better quality and
      competitive advantages. Nevertheless, it requires a new understanding of
      innovation processes which considers value for patients and quality of results
      and outcome as a relevant scale for measuring effects of change management.
      Finally, the methods of the assessment of user oriented healthcare delivery are
      an essential challenge for the evaluation of cooperative healthcare services.

PMID- 22142886
TI  - ["Isoappearance": a pressing need for prescribing by active ingredient (official
      spanish denomination)].

PMID- 22142887
TI  - Pathology associated with a human case of rabies in the United Kingdom caused by
      European bat lyssavirus type-2.
AB  - Human infection with the rabies-related virus European bat lyssavirus type-2
      (EBLV-2) has only been reported on two occasions. Here we report the pathology
      observed within spinal cord and visceral tissues associated with EBLV-2 infection
      for the first time. Neuronal labelling with an anti-rabies nucleocapsid
      monoclonal antibody was observed and appeared indistinguishable from the
      labelling reported from human infection with rabies virus.

PMID- 22142888
TI  - Akt and p53 are potential mediators of reduced mammary tumor growth by cloroquine
      and the mTOR inhibitor RAD001.
AB  - PI3K/Akt/mTOR and p53 signaling pathways are frequently deregulated in tumors.
      The anticancer drug RAD001 (everolimus) is a known mTOR-inhibitor, but mTOR
      inhibition leads to phosphorylation of Akt inducing resistance against RAD001
      treatment. There is growing evidence that conflicting signals transduced by the
      oncogene Akt and the tumorsuppressor p53 are integrated via negative feedback
      between the two pathways. We previously showed that the anti-malarial
      Chloroquine, a 4-alkylamino substituted quinoline, is a p53 activator and reduced
      the incidence of breast tumors in animal models. Additionally, Chloroquine is an
      effective chemosensitizer when used in combination with PI3K/Akt inhibitors but
      the mechanism is unknown. Therefore, our aim was to test, if Chloroquine could
      inhibit tumor growth and prevent RAD001-induced Akt activation. Chloroquine and
      RAD001 caused G1 cell cycle arrest in luminal MCF7 but not in mesenchymal MDA-MB
      231 breast cancer cells, they significantly reduced MCF7 cell proliferation on a
      collagen matrix and mammospheroid formation. In a murine MCF7 xenograft model,
      combined treatment of Chloroquine and RAD001 significantly reduced mammary tumor
      growth by 4.6-fold (p = 0.0002) compared to controls. Chloroquine and RAD001
      inhibited phosphorylation of mTOR and its downstream target, S6K1. Furthermore,
      Chloroquine was able to block the RAD001-induced phosphorylation of Akt serine
      473. The Chloroquine effect of overcoming the RAD001-induced activation of the
      oncogene Akt, as well as the promising antitumor activity in our mammary tumor
      animal model present Chloroquine as an interesting combination partner for the
      mTOR-inhibitor RAD001.

PMID- 22142889
TI  - A novel test to determine the significance of neural selectivity to single and
      multiple potentially correlated stimulus features.
AB  - Mutual information is a principled non-linear measure of dependence between
      stochastic variables, which is widely used to study the selectivity of neural
      responses to external stimuli. Here we define and develop a set of novel
      statistical independence tests based on mutual information, which quantify the
      significance of neural selectivity to either single features or to multiple,
      potentially correlated stimulus features like those often present in naturalistic
      stimuli. If the values of different features are correlated during stimulus
      presentation, it is difficult to establish if one feature is genuinely encoded by
      the response, or if it instead appears to be encoded only as a side effect of its
      correlation with another genuinely represented feature. Our tests provide a way
      to disambiguate between these two possibilities. We use realistic simulations of
      neural responses tuned to one or more correlated stimulus features to investigate
      how limited sampling bias correction procedures affect the statistical power of
      such independence tests, and we characterize the regimes in which the
      distribution of information values under the null hypothesis can be approximated
      by simple distributions (Chi-square or Gaussian). Finally, we apply these tests
      to experimental data to determine the significance of tuning of the band limited
      power (BLP) of the gamma [30-100 Hz] frequency range of the primary visual
      cortical local field potential to multiple correlated features during
      presentation of naturalistic movies. We show that gamma BLP carries significant,
      genuine information about orientation, space contrast and time contrast, despite
      the strong correlations between these features.

PMID- 22142891
TI  - Daily intake of Lactobacillus casei Shirota increases natural killer cell
      activity in smokers.
AB  - Dietary probiotics supplementation exerts beneficial health effects. Since
      cigarette smoking reduces natural killer (NK) activity, we evaluated the effect
      of Lactobacillus casei Shirota (LcS) intake on NK cytotoxic activity in male
      smokers. The double-blind, placebo-controlled, randomised study was conducted on
      seventy-two healthy Italian blue-collar male smokers randomly divided for daily
      intake of LcS powder or placebo. Before and after 3 weeks of intake, peripheral
      blood mononuclear cells were isolated and NK activity and CD16+ cells' number
      were assessed. Daily LcS intake for 3 weeks significantly increased NK activity
      (P < 0.001). The increase in NK activity was paralleled by an increase in CD16+
      cells (P < 0.001). Before intake, NK cytotoxic activity inversely correlated with
      the number of cigarettes smoked (R - 0.064). LcS intake prevented the smoke
      dependent expected NK activity reduction. The analysis of the distribution of
      changes in smoke-adjusted NK activity demonstrated that the positive variations
      were significantly associated with LcS intake, while the negative variations were
      associated with placebo intake (median value of distributions of differences,
      20.98 lytic unit (LU)/107 cells for LcS v. - 4.38 LU/107 cells for placebo, P =
      0.039). In conclusion, 3 weeks of daily LcS intake in Italian male smokers was
      associated with a higher increase in cytotoxic activity and CD16+ cells' number
      in comparison to the placebo intake group.

PMID- 22142892
TI  - Interactions between cadmium and lead with acidic soils: experimental evidence of
      similar adsorption patterns for a wide range of metal concentrations and the
      implications of metal migration.
AB  - The importance of high- and low-affinity surface sites for cadmium and lead
      adsorption in typical European and Asian soils was investigated. Adsorption
      experiments on surface and deep horizons of acidic brown (Vosges, France) and red
      loess soils (Hunan, China) were performed at 25 degrees C as a function of the pH
      (3.5-8) and a large range of metal concentrations in solution (10(-9)-10(-4) mol
      l(-1)). We studied the adsorption kinetics using a Cd(2+)-selective electrode and
      desorption experiments as a function of the solid/solution ratio and pH. At a
      constant solution pH, all samples exhibited similar maximal adsorption capacities
      (4.0 +/- 0.5 MUmol/g Cd and 20 +/- 2 MUmol/g Pb). A constant slope of adsorbed
      dissolved concentration dependence was valid over 5 orders of magnitude of metal
      concentrations. Universal Langmuir and Freundlich equations and the SCM formalism
      described the adsorption isotherms and the pH-dependent adsorption edge over very
      broad ranges of metal concentrations, indicating no high- or low-affinity sites
      for metal binding at the soil surface under these experimental conditions. At pH
      5, Cd and Pb did not compete, in accordance with the SCM. The metal adsorption
      ability exceeded the value for soil protection by two orders of magnitude, but
      only critical load guarantees soil protection since metal toxicity depends on
      metal availability.

PMID- 22142890
TI  - Environmental exposure, estrogen and two X chromosomes are required for disease
      development in an epigenetic model of lupus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease primarily afflicting
      women. The reason for the gender bias is unclear, but genetic susceptibility,
      estrogen and environmental agents appear to play significant roles in SLE
      pathogenesis. Environmental agents can contribute to lupus susceptibility through
      epigenetic mechanisms. We used (C57BL/6xSJL)F1 mice transgenic for a dominant
      negative MEK (dnMEK) that was previously shown to be inducibly and selectively
      expressed in T cells. In this model, induction of the dnMEK by doxycycline
      treatment suppresses T cell ERK signaling, decreasing DNA-methyltransferase
      expression and resulting in DNA demethylation, overexpression of immune genes
      Itgal (CD11a) and Tnfsf7 (CD70), and anti-dsDNA antibody. To examine the role of
      gender and estrogen in this model, male and female transgenic mice were neutered
      and implanted with time-release pellets delivering placebo or estrogen.
      Doxycycline induced IgG anti-dsDNA antibodies in intact and neutered, placebo
      treated control female but not male transgenic mice. Glomerular IgG deposits were
      also found in the kidneys of female but not male transgenic mice, and not in the
      absence of doxycycline. Estrogen enhanced anti-dsDNA IgG antibodies only in
      transgenic, ERK-impaired female mice. Decreased ERK activation also resulted in
      overexpression and demethylation of the X-linked methylation-sensitive gene
      CD40lg in female but not male mice, consistent with demethylation of the second X
      chromosome in the females. The results show that both estrogen and female gender
      contribute to the female predisposition in lupus susceptibility through hormonal
      and epigenetic X-chromosome effects and through suppression of ERK signaling by
      environmental agents.

PMID- 22142893
TI  - Australian mental health tribunals--'Space' for rights, protection, treatment and
      governance?
AB  - This paper draws on a multi-year Australian collaborative study of mental health
      review tribunals ('MHTs') in three jurisdictions (Victoria, New South Wales and
      the Australian Capital Territory) undertaken in conjunction with the NSW Law and
      Justice Foundation, using qualitative and quantitative methods to examine the
      role of MHTs in advancing goals such as fairness, legality and access to
      treatment. Study findings regarding stakeholder and client concerns - about
      access to quality treatment and associated support services, review of treatment
      adequacy and drug regimes, and their 'participation' or dignity of engagement in
      review processes - are presented as variants of the need for adequate hearing
      'space': temporal, jurisdictional, cognate/relational, physical and symbolic, and
      'connective'. Building on earlier arguments for MHTs to engage not only legal,
      but also clinical and social domains, and for adopting some processes more
      characteristic of case-conferencing, this paper examines the implications of
      tribunal 'flexibility' and a wider overall 'governance' jurisdiction in mental
      health.

PMID- 22142894
TI  - Public opinion on media presence in the courthouse.
AB  - Very little attention has been devoted to the public's opinion of media coverage
      of court cases despite extensive research on pretrial publicity (PTP). Following
      a provincial judgment to restrict media access in Quebec courthouses, a
      preliminary unpublished study found that the public was largely in support of
      these restrictions. The present study sought to expand on this finding in a more
      widely generalizable sample. Subjects were recruited from continuing education
      classes and completed a questionnaire that assessed their support for restricting
      journalists in courthouses. Nearly 80% of the 243 participants supported media
      restrictions. Although participants in the four experimental conditions and one
      of the control groups were largely in favor of the restrictions, one control
      group was opposed to the restrictions. The results suggest that the public
      prefers that journalists have restricted access to courtroom participants,
      resonating research on PTP and the Supreme Court's decision on the case.

PMID- 22142895
TI  - Choosing to limit choice: Self-binding directives in Dutch mental health care.
AB  - In certain cases of chronic mental illness (for example bipolar disorder) a self
      binding directive or Ulysses contract may be a helpful intervention to prevent
      harm to the person him- or herself and/or others. By choosing such an
      arrangement, the patient can indicate when and how mental health professionals
      may intervene against his or her will and provide indicated care which may lead
      to an improvement of the patient's mental condition. In the Netherlands, since
      2008 the Compulsory Admissions Act has been amended and now includes a paragraph
      on self-binding. Starting from the Dutch debate and statutory regulation of self
      binding in mental health care, a number of issues with broader relevance are
      discussed, particularly as these pertain to the legal regulation and
      juridification of self-binding. It is argued that too many detailed rules are a
      threat to increasing patient empowerment.

PMID- 22142896
TI  - Attention deficit hyperactivity disorder does not predict criminal recidivism in
      young adult offenders: Results from a prospective study.
AB  - As the state of research on the relationship between attention deficit
      hyperactivity disorder (ADHD) and recidivism can be considered controversial, our
      prospective study investigated whether ADHD predicts recidivism in a sample of
      283 male, German, young adult prisoners. Currently existing ADHD symptoms and
      symptoms that were present in childhood were screened according to the DSM-IV
      checklist criteria. Information on general and violent recidivism was gathered
      using government records with a follow-up period of up to five years. The
      prevalence of adult ADHD was six times greater than in the general population,
      and the number of participants who retrospectively met the criteria for a
      diagnosis with ADHD in childhood was ten times greater than found in community
      samples. Survival analyses did not identify ADHD as a predictor of recidivism.
      Controlling for conduct disorder, substance dependence, and other relevant
      variables did not alter results. However, among individuals who were released
      from prison and then reconvicted for a new crime, offenders diagnosed with ADHD
      were found to reoffend sooner after release. These findings stress the necessity
      of differentiating between risk factors for delinquency and risk factors for
      recidivism.

PMID- 22142897
TI  - Epidemiology of scabies in the West Bank, Palestinian Territories (Occupied).
AB  - BACKGROUND: Scabies is a disease that is considered a public health problem in
      the Palestinian Territories and in other countries around the world. Scabies
      causes skin lesions leading to substantial morbidity, and is also associated with
      social stigma. In this study we describe the epidemiology of scabies in the West
      Bank, Palestine during the years 2005-2010. METHODS: We examined the records and
      profiles of a total of 1734 patients who were admitted to the dermatology clinics
      of the Palestinian Ministry of Health in 2005-2010. RESULTS: The disease was
      found to be prevalent in all governorates. The average annual incidence of
      scabies in the West Bank for 2005-2010 was 17/100,000 population. The average
      number of scabies patients per year in the West Bank was 26.3 per governorate,
      with a significant increase in the years 2009 and 2010 (p<0.001). Disease
      occurrence was significantly higher among children aged <= 10 years than in the
      other age groups, in adult females in the age groups of 31-40 and 41-50 years
      compared to males in these age groups, and in males in the age group of 11-20
      years compared to females in that age group. CONCLUSIONS: Scabies was found in
      all governorates of the Palestinian West Bank. Individuals under 20 years of age
      are particularly at risk. Compulsory reporting of scabies to the Palestinian
      Ministry of Health would be expected to increase awareness of the disease, which
      is crucial for the prevention and control of scabies in the Palestinian
      Territories.

PMID- 22142898
TI  - The effect of iron on cognitive development and function in infants, children and
      adolescents: a systematic review.
AB  - A systematic review was conducted to summarize the evidence currently available
      from randomized controlled trials (RCTs) concerning the effect of iron intake of
      infants, children and adolescents on measures of cognitive development and
      function. The Cochrane Library, MEDLINE and Embase were searched up to and
      including February 2010. Studies were also identified by checking the
      bibliographies of the articles retrieved. All RCTs with an adequate control group
      in which iron supply was provided by natural food sources, fortified foods,
      formula or supplements to infants, children or adolescents until the age of 18
      years were considered for inclusion. No language restrictions were applied.
      Fourteen studies met the selection criteria. Twelve out of these 14 studies had a
      high or moderate risk of bias. A large degree of heterogeneity of study
      populations, iron dosages and outcome measures precluded performing a
      quantitative meta-analysis. Overall, the studies suggest a modest positive effect
      of iron supplementation on cognition and psychomotor outcomes in anemic infants
      and children after supplementation periods of at least 2 months of duration.

PMID- 22142899
TI  - The grid-walking test: assessment of sensorimotor deficits after moderate or
      severe dopamine depletion by 6-hydroxydopamine lesions in the dorsal striatum and
      medial forebrain bundle.
AB  - The present study aims to evaluate the applicability of the grid-walking test in
      rats with moderate or severe dopamine-depletion incurred by unilateral nigro
      striatal 6-hydroxydopamine (6-OHDA) lesions. Striatum samples were analyzed by
      high pressure liquid chromatography coupled to electrochemical detection (HPLC
      EC) after behavioral testing. In Experiment 1, 2 weeks after the injection of 6
      OHDA into the medial forebrain bundle, adult Wistar rats were divided into an l
      3,4-dihydroxyphenylalanine (L-dopa) and a vehicle treatment group and their
      behaviors on the grid were compared. The severely lesioned animals (mean dopamine
      depletion of 92%) did not exhibit behavioral asymmetry in the number of
      contralateral foot-slips. However, L-dopa administration selectively reduced the
      number of foot-slips of the contralateral forelimb when compared with the vehicle
      group. In Experiment 2, 6-OHDA was injected into the dorsal striatum and foot
      slips on the grid were analyzed 4, 9 and 13 days following the lesion. The rats
      with moderate dopamine-depletion (mean depletion of 54%) exhibited more
      contralateral forelimb-slips on all testing days. Compared with naive rats,
      hemiparkinsonian rats also showed more forelimb-slips. These results suggest that
      the grid-walking test should be a powerful and sensitive behavioral assay for
      sensory-motor deficits in rat models of nigro-striatal dopamine lesions.

PMID- 22142901
TI  - Community health centers: providers, patients, and content of care.
AB  - For more than 40 years, community health centers (CHCs) have provided primary
      care and behavioral and mental health services in medically underserved
      communities, regardless of a patient's ability to pay. In 2001, the government
      launched the Federal Health Center Growth Initiative, providing funds over 5
      years to increase by 60% the number of patients served in 1,200 communities. As
      the number of CHCs has expanded, demand for both physician and nonphysician
      practitioner services has increased. This report compares patient and encounter
      characteristics across the different types of providers seen at CHC visits during
      a 3-year period, 2006-2008.

PMID- 22142900
TI  - Expression and localization of the cannabinoid receptor type 1 and the enzyme
      fatty acid amide hydrolase in the retina of vervet monkeys.
AB  - The presence of a widespread endocannabinoid (eCB) system within the nervous
      system, including the retina, has been demonstrated in recent years. Expression
      patterns of the cannabinoid receptor type 1 (CB1R) and enzyme fatty acid amide
      hydrolase (FAAH) are available for rodents, but data for humans and monkeys are
      scarce. We, therefore, thoroughly examined the distribution pattern of CB1R and
      FAAH throughout the retina of the vervet monkey (Chlorocebus sabeus) using
      confocal microscopy. Our results demonstrate that CB1R and FAAH are expressed
      throughout the retina, from the foveal pit to the far periphery. CB1R and FAAH
      are present in the photoreceptor, outer plexiform, inner nuclear, inner
      plexiform, and retinal ganglion cell layers (PRL, OPL, INL, IPL, and RGCL,
      respectively). More specifically, in PRL, CB1R and FAAH are preferentially
      expressed in cones of the central retina. In OPL, these two components of the eCB
      system are concentrated not only in the cone pedicles but also in rod spherules
      with, however, a less intense staining pattern. Triple-labeling
      immunofluorescence revealed that both cone and rod bipolar cells express CB1R and
      FAAH. Heavy staining is detected in RGC somas and axons. Neither CB1R nor FAAH
      are found in the retinal glia, the Muller cells. These data indicate that the eCB
      system is present throughout the primate retina and is ideally positioned to
      modulate central and peripheral retinal functions.

PMID- 22142902
TI  - Mdp3 is a novel microtubule-binding protein that regulates microtubule assembly
      and stability.
AB  - Microtubule-binding proteins are a group of molecules that associate with
      microtubules, regulate the structural properties of microtubules, and thereby
      participate in diverse microtubule-mediated cellular activities. A recent mass
      spectrometry-based proteomic study has identified microtubule-associated protein
      7 (MAP7) domain-containing 3 (Mdp3) as a potential microtubule-binding protein.
      However, its subcellular localization and functional importance are not
      characterized. In this study, by GST-pulldown assays, we found that Mdp3
      interacted with tubulin both in cells and in vitro. Immunofluorescence microscopy
      and microtubule cosedimentation assays revealed that Mdp3 also associated with
      microtubules. Serial deletion experiments showed that the two coiled coil motifs
      of Mdp3 were critical for its interaction with tubulin and microtubules. Cold
      recovery and nocodazole washout assays further demonstrated an important role for
      Mdp3 in regulating cellular microtubule assembly. Our data also showed that Mdp3
      significantly enhanced the stability of cellular microtubules. By tubulin
      turbidity assay, we found that Mdp3 could promote microtubule assembly and
      stability in the purified system. In addition, we found that Mdp3 expression
      varied during the cell cycle and in primary tissues. These findings thus
      establish Mdp3 as a novel microtubule-binding protein that regulates microtubule
      assembly and stability.

PMID- 22142903
TI  - Mathematical modeling of cryoprotectant addition and removal for the
      cryopreservation of engineered or natural tissues.
AB  - Long-term storage of natural tissues or tissue-engineered constructs is critical
      to allow off-the-shelf availability. Vitrification is a method of
      cryopreservation that eliminates ice formation, as ice may be detrimental to the
      function of natural or bioartificial tissues. In order to achieve the vitreous
      state, high concentrations of CPAs must be added and later removed. The high
      concentrations may be deleterious to cells as the CPAs are cytotoxic and single
      step addition or removal will result in excessive osmotic excursions and cell
      death. A previously described mathematical model accounting for the mass transfer
      of CPAs through the sample matrix and cell membrane was expanded to incorporate
      heat transfer and CPA cytotoxicity. Simulations were performed for two systems,
      an encapsulated system of insulin-secreting cells and articular cartilage, each
      with different transport properties, geometry and size. Cytotoxicity and mass
      transfer are dependent on temperature, with a higher temperature allowing more
      rapid mass transfer but also causing increased cytotoxicity. The effects of
      temperature are exacerbated for articular cartilage, which has larger dimensions
      and slower mass transport through the matrix. Simulations indicate that addition
      and removal at 4 degrees C is preferable to 25 degrees C, as cell death is higher
      at 25 degrees C due to increased cytotoxicity in spite of the faster mass
      transport. Additionally, the model indicates that less cytotoxic CPAs, especially
      at high temperature, would significantly improve the cryopreservation outcome.
      Overall, the mathematical model allows the design of addition and removal
      protocols that insure CPA equilibration throughout the sample while still
      minimizing CPA exposure and maximizing cell survival.

PMID- 22142905
TI  - Clinical molecular imaging with radiotracers: current status.
AB  - Molecular imaging is defined as the visualization, characterization, and
      measurement of biological processes at the molecular and cellular levels in
      humans and other living systems. Most clinical molecular imaging is currently
      done using radioisotope-labeled agents to define the activity of various
      metabolic pathways in vivo or to determine the distribution and density of
      various receptors relevant to human disease. This paper briefly reviews most of
      the commonly used radiopharmaceuticals in nuclear medicine, as well as newer
      agents that are likely to become available in the near future. The metabolic
      pathways include those relevant to the thyroid, parathyroid, heart, brain, bones,
      kidneys, liver, pancreas, adrenals and tumor. The receptor systems include agents
      useful in evaluating movement disorders, dementia, cardiac sympathetic enervation
      and neoangiogenesis. Receptor systems relevant to tumors include somatostatin
      receptors (neuroendocrine tumors), prostate-specific membrane antigen, carbonic
      anhydrase IX (renal cancer), and CD-20 (lymphoma). These agents, and newer agents
      that are being developed, are likely to become critical in the development of
      personalized medicine, where it will become increasingly important to determine
      whether a treatment that is targeted to a specific metabolic pathway or receptor
      is likely to be successful.

PMID- 22142904
TI  - Response inhibition and error monitoring during a visual go/no-go task in inuit
      children exposed to lead, polychlorinated biphenyls, and methylmercury.
AB  - BACKGROUND: Lead (Pb) and polychlorinated biphenyls (PCBs) are neurotoxic
      contaminants that have been related to impairment in response inhibition.
      OBJECTIVES: In this study we examined the neurophysiological correlates of the
      response inhibition deficits associated with these exposures, using event-related
      potentials (ERPs) in a sample of school-age Inuit children from Arctic Quebec
      exposed through their traditional diet. METHODS: In a prospective longitudinal
      study, we assessed 196 children (mean age, 11.3 years) on a visual go/no-go
      response inhibition paradigm. Pb, PCB, and mercury (Hg) concentrations were
      analyzed in cord and current blood samples. Hierarchical multiple regression
      analyses were conducted to examine the associations of contaminant levels to
      go/no-go performance (mean reaction time, percent correct go, percent correct no
      go) and five ERPs [N2, P3, error-related negativity, error positivity (Pe), and
      correct response positivity (Pc)] after control for confounding variables.
      RESULTS: Current blood Pb concentrations were associated with higher rates of
      false alarms and with decreased P3 amplitudes to go and no-go trials. Current
      plasma PCB-153 concentrations were associated with slower reaction times and with
      reduced amplitudes of the Pe and Pc response-related potentials. Hg
      concentrations were not related to any outcome on this task but showed
      significant interactions with other contaminants on certain outcomes.
      CONCLUSIONS: These results suggest that Pb exposure during childhood impairs the
      child's ability to allocate the cognitive resources needed to correctly inhibit a
      prepotent response, resulting in increased impulsivity. By contrast, postnatal
      PCB exposure appears to affect processes associated with error monitoring, an
      aspect of behavioral regulation required to adequately adapt to the changing
      demands of the environment, which results in reduced task efficiency.

PMID- 22142906
TI  - C1q regulates collagen-dependent production of reactive oxygen species,
      aggregation and levels of soluble P-selectin in whole blood.
AB  - Blood platelets express several receptors involved in immunity (e.g. complement-,
      toll-like- and Fcgamma-receptors) and release inflammatory mediators.
      Furthermore, formation of platelet-leukocyte aggregates has an important role
      during inflammatory conditions such as coronary artery disease. Thus, apart from
      their well-known role in haemostasis, platelets are today also recognized as
      cells with immuno-modulatory properties. We have previously reported regulatory
      effects of complement protein 1q (C1q) on platelet activation in experimental
      setups using isolated cells. In the present study we have proceeded by
      investigating effects of C1q on collagen-induced aggregation, production of
      reactive oxygen species (ROS), formation of platelet-leukocyte aggregates and
      levels of soluble P-selectin in whole blood. Impedance measurements showed that
      C1q inhibited collagen-induced aggregation whereas it potentiated the collagen
      provoked production of ROS in a luminol-dependent chemiluminescence assay. The
      effects of C1q on aggregation and ROS-production were dependent upon platelets,
      as they were no longer observed in presence of the platelet (GpIIb/IIIa)
      inhibitor Reopro. Furthermore, the levels of soluble P-selectin were found to be
      lowered upon treatment with C1q prior to addition of collagen. There was also a
      trend towards a decreased formation of large platelet-leukocyte aggregates in
      collagen-stimulated whole blood following C1q treatment. In conclusion, our data
      indicate that C1q could have a role in regulating platelet activation and
      associated leukocyte recruitment during vessel wall injury. This has implications
      for inflammatory disorders such as coronary artery disease.

PMID- 22142907
TI  - Creating and nurturing academic-service partnerships and educational
      collaboratives.

PMID- 22142908
TI  - The time is right-the time is now...academic-service partnerships need to be
      revisited.

PMID- 22142909
TI  - A model of new nurse transition.
AB  - The progression from nursing student into the RN role remains difficult, despite
      over 30 years of effort to ease the transition for new graduates. We review the
      research on programs designed to help new graduates move into practice and
      propose a model for new nurse transition that starts during nursing education and
      continues 2 years into practice. The model illustrates the frequent detachment
      between efforts taken by nursing schools and employers to facilitate this
      transition. We offer recommendations for the design of future research to capture
      all transition efforts, from student to functioning RN, and better identify the
      critical elements of new nurse transition programs. Evidence such as this is
      needed to allow schools and employers to use their limited resources most
      effectively to support graduate nurses.

PMID- 22142910
TI  - Professionalization and retention outcomes of a university-service mentoring
      program partnership.
AB  - With the use of a university-service partnership to introduce mentoring and
      shared governance, the aim of this study was to evaluate the effect of these
      interventions on nurse perceptions of the supportive culture of the workplace
      environment, professional skill development, decisional involvement, and
      retention and vacancy rates. A nonequivalent pretest-posttest, noncontrol group
      design was used with mentors of newly hired mentees to evaluate their workplace
      perspectives following mentor classes, ongoing mentor support, and a formal
      mentor-management workforce governance board. A convenience sample of 89 RNs from
      two acute care facilities attended mentoring and professionalization classes and
      worked with 109 mentees over 1-3 years. Mentors reported improved teamwork and
      the ability to deal with conflict but wanted more administrative oversight of the
      quality and scope of practice of support staff and additional interdepartmental
      collaboration. One hospital's vacancy rate decreased by 80%, and the other
      facility's retention rate improved by 21%. The data suggest that a mentor program
      with comprehensive education and mentor-management alliances through formal
      workforce environment governance enhances professionalization of frontline nurses
      and helps sustain a positive, constructive workplace environment. Mentoring
      classes on communication and cultural sensitivity skills and other leadership
      concepts, followed by mentor support and mentor-administrative forums, have
      positive implications for sustained improvement of a supportive culture as
      perceived by hospital-based RNs and new nurse graduates.

PMID- 22142911
TI  - International doctoral education partnership: the first full-time doctoral
      program for nurses in china.
AB  - In July 2008, five nurses graduated from the first full-time doctoral program for
      nurses in China at Peking Union Medical College (PUMC) in Beijing. The purpose of
      this article is to describe the doctoral program partnership between the Schools
      of Nursing at PUMC and Johns Hopkins University (Hopkins) in the United States
      that led to this historic event. The planning, implementation, evaluation, and
      early outcomes of the program are described to provide a model for rapidly
      increasing capacity for doctoral education in nursing in countries without
      sufficient or any doctoral education in nursing. One of the main objectives of
      this doctoral program partnership was to transition the Chinese University to an
      independent doctoral program as rapidly as possible. Lessons learned are
      presented as well as the next steps for this program.

PMID- 22142912
TI  - When a natural disaster occurs: lessons learned in meeting students' needs.
AB  - Across the nation, weather-related natural disasters-tropical storms, floods,
      tornadoes, and earthquakes-struck even areas where weather concerns are not
      paramount on the minds of most people. These natural disasters heightened
      awareness that all geographic areas are susceptible to aberrant weather
      conditions. The purpose of this article was to relate the lessons learned by one
      academic health center in meeting students' emergency preparedness and disaster
      recovery needs following a major hurricane in fall 2008. To gauge students' storm
      related needs, a Hurricane Needs Survey (HNS) was conducted in spring 2009, 7
      months after the hurricane. Students responded to 26 structured response items
      and 3 open-ended questions. Five hundred fifteen surveys were completed,
      constituting a response rate of 37.2%. Data were analyzed by creating frequencies
      to profile students' hurricane experiences. Results indicated that all students
      left the island under mandatory evacuation orders; most stayed with their
      families, and most experienced moderate material losses. For some students, the
      evacuation process and life after the storm contributed to ongoing problems,
      worries, and academic performance issues. Qualitative content analysis was used
      to derive themes from the students' narrative responses to the HNS open-ended
      questions about their perceptions of the extent to which the University of Texas
      Medical Branch met their needs. When students' hurricane response comments were
      analyzed, three major themes emerged: being prepared, needing to be connected,
      and returning to normalcy. The major lessons learned are that the emergency
      preparation of students requires greater specificity and that discussion about
      poststorm recovery expectations is essential. Following a natural disaster,
      students experience more distress than may be readily apparent.

PMID- 22142913
TI  - Teaching evidence-based practice: the Bachelor of Science in nursing essentials
      at work at the bedside.
AB  - Patient safety and quality outcomes are major issues in the health care industry.
      Many national organizations have pushed these issues to the forefront of health
      care, demanding that health care professionals, especially nurses, play a vital
      role and be vigilant in these endeavors. Nurse educators, using The Essentials of
      Baccalaureate Education for Professional Nursing Practice, are in a unique
      position to impact health care systems and patient care by educating and training
      nursing students in the skills necessary to promote safety and quality outcomes.
      This article describes a creative, authentic learning experience that is
      currently being used in a Bachelor of Science in Nursing (BSN) program. The
      learning experience is a shared partnership between the clinical agency, the
      faculty, and the health science librarian to assist senior nursing students in
      the last semester of their baccalaureate degree program to synthesize and use the
      knowledge, skills, and attitudes that promote patient safety and optimal
      outcomes. It is a teaching strategy that incorporates many of the outcomes from
      the BSN Essentials and aids students to actively seek and deliver care using
      evidence-based practice.

PMID- 22142914
TI  - Challenge with care: reflections on teaching excellence.
AB  - A number of faculty have had no formal preparation to teach. Because little
      nursing research has focused on teaching excellence in recent years, when both
      nursing practice and approaches to teaching and learning have changed remarkably,
      this analysis integrates present perspectives and the research foundation for
      teaching nursing. A constant comparative method incorporating 27 doctoral student
      reflections and analysis of literature from 1960 to present resulted in four
      major categories: know and honor students, enthused, knowledgeable, and student
      centered. Linking the major categories, an Excellent Teacher Circle of
      Distinction emerged, described as "with enthusiasm and compassion the teacher
      engages the students and invites learning in a non-judgmental manner, yet,
      expectations of reciprocal respect and perseverance are present." Better
      understanding of this foundation can provide direction for those new to teaching,
      as well as experienced faculty, so as to better prepare the nurses of tomorrow.

PMID- 22142915
TI  - Using The Essentials of Baccalaureate Education for Professional Nursing Practice
      (2008) as a framework for curriculum revision.
AB  - Curriculum development is often seen as an arduous process by faculty in nursing
      education. Curriculum revisions need to take place based on profound changes in
      science, a more complex health care system, technology, and more current models
      of curriculum design. The American Association of Colleges of Nursing's The
      Essentials of Baccalaureate Education for Professional Nursing Practice is an
      organizational framework that can easily be used during a nursing program's
      curriculum revision process. The redesign of nursing curricula is urgent and
      needs to reflect the integration of clinical and classroom learning consistent
      with the language found in the Baccalaureate Essentials, standards of the
      institutions' accrediting bodies, and the state boards of nursing. An additional
      consideration to ensure high-quality nursing education and student outcomes is to
      include a review of the National Council State Board of Nursing's Test Plan to
      identify gaps in content identified as essential to safe practice.

PMID- 22142916
TI  - Digging deeper: nurse excess or shortage? The effect on a new nurse.
AB  - The past decade has experienced great success in publicizing and decreasing the
      nursing shortage. Articles describing the shortage continue with impressive but
      disparate projections of its dimension. New degree programs have been created and
      established programs expanded as increasing numbers of students answer the call,
      and there are signs that the publicity has succeeded. Recent graduates have
      experienced difficulties finding employment or postgraduate training positions,
      which prompt a more detailed look at the numbers. Previously published research
      projects the nurse shortage for the year 2025 to lie somewhere between 500,000
      and 1,000,000 nurses. If it is presumed that these numbers refer to RNs only,
      then the net of dropout, retirement, and graduation rates suggests that this
      projected shortage could be misleading. Articles describing the shortage
      typically exclude detailed supply-and-demand statistics to support their
      projections. The projected 2025 deficit of nurses is estimated by one source at
      500,000. Currently, nursing programs are graduating more than 100,000 and
      boarding 50,000 new 4-year-degree RNs per year. According to the National Health
      Service, more than 10,000 nurses retire each year, yielding a net addition of
      40,000 new nurses per year, which yields a net supply by 2025 of 600,000. It
      seems that the more than 3,000 nursing schools are already graduating enough
      nurses to carry the loss. The universities have increased the supply of nurse
      graduates; now, the real shortcoming lays in the dearth of nurse residency
      programs that help transition the new nurses from the books to the bedside. Most
      nursing jobs require a year of experience, a luxury allowed by the increased
      graduates and decreased shortage. The real crisis now appears to be a logjam
      caused by the increased supply with the near absence of transition training. The
      resulting frustration of the new graduates, if not fixed, is likely to have
      adverse affects on retention and supply.

PMID- 22142917
TI  - A faculty development collaborative in interprofessional simulation.
AB  - This article describes a project that was funded through the Texas Center for
      Nursing Workforce Studies and the Texas Team. A strategic plan presented to the
      governor of Texas in 2008 by the Texas Team provided strategies addressing
      nursing education capacity in Texas, with the goal of increasing the number of
      nursing graduates to meet forecasted needs. The Central Texas Region identified
      the increasing use of clinical simulation as one way to meet a subset of goals
      and objectives of the plan. With this pedagogy being new, it was determined
      through a needs assessment that faculty development in simulation was a priority.
      This article will discuss the collaboration of 12 nursing programs and practice
      partners to provide faculty development in clinical simulation. Four workshops
      were held across the region, during which time six interprofessional simulation
      scenarios were written and clinical simulation experts identified at each of the
      schools and participating practice facilities. As a result of the faculty
      development in clinical simulation, 80% of the respondents reported that
      simulation has increased in their nursing programs, and 30% reported having
      increased student enrollment because of the faculty's ability to increase the use
      of simulation.

PMID- 22142918
TI  - Preparing clinically expert faculty educators: an academic partnership model.
AB  - To increase nursing education capacity in New Jersey, the Robert Wood Johnson
      Foundation (RWJF) New Jersey Nursing Initiative (NJNI) awarded grants to prepare
      graduate nursing students to become clinically expert faculty. The purpose of
      this article was to describe the experiences of a collaborative partnership in
      preparing 14 scholars for the faculty role. The partnership developed two
      innovative models of preparing faculty with clinical expertise. The curriculum of
      the Fairleigh Dickinson University Adult Nurse Practitioner program was enhanced
      with education courses and intensive teaching practicum. The curriculum of the
      Monmouth University Nursing Education program was enhanced with more intensive
      clinical immersion in a selected concentration. Both models were based on the
      National League for Nursing nurse educator competencies (J. A. Halstead, 2007).
      The RWJF scholars were socialized into the faculty role from the start of the
      program through curricular and extracurricular activities. To date, all
      components of the enhanced curriculum were implemented with plans for sustaining
      the programs and partnership. Of 14 scholars, 4 graduated, and 10 are on track to
      graduate as projected. The curriculum enhancements improved two successful
      master's programs preparing graduates for not one, but two advanced practice
      roles.

PMID- 22142919
TI  - A successful academic collaborative to increase nurse faculty in New Jersey.
AB  - The purpose of this article was to describe a successful academic collaboration
      of 4 New Jersey state colleges and universities. The aim of the collaborative is
      to prepare and graduate students in a dual role as advanced clinical/practice
      nurses and nurse faculty within an innovative master of nursing educational
      program. This effort was funded by a 4-year grant from the Robert Wood Johnson
      Foundation NJ Nursing Initiative and the New Jersey Chamber of Commerce. The New
      Jersey Nursing Education Collaborative (NJNEC) is discussed using E. O'Neil and
      P. Krauel's (2004) factors for an effective collaborative. The four factors for
      an effective partnership include a coherent institutional strategy, partners that
      bring value and assets to the collaborative, mutually beneficial goals, and
      accountability to each other. The NJNEC is composed of four independent state
      colleges and universities with separate governing structures and student
      characteristics. The four schools are located in different geographical locations
      in the state. Several challenging issues in preparation of faculty and
      maintaining a collaborative will be presented for future consideration.

PMID- 22142920
TI  - Thinking strategically: academic-practice relationships: one health system's
      experience.
AB  - Strategic planning and joint leverage of the strengths inherent in the academic
      and practice arenas of nursing are imperative to confront the challenges facing
      the profession of nursing and its place within the healthcare team of the future.
      This article presents a description and discussion of the implementation of
      several academic-practice partnership initiatives by Meridian Health, a health
      system located in central New Jersey. Included in the strategies discussed are
      creation of a support program for nonprofessional employees to become registered
      nurses; active partnership in the development of an accelerated BSN program;
      construction of support systems and academic partnerships for staff participation
      in RN-to-BSN programs; construction of on-site clinical simulation laboratories
      to foster interprofessional learning; and the implementation of a new BSN
      program, the first and only generic BSN program in two counties of the state.
      Outcomes of these academic-practice partnerships also are presented, including
      number of participants; graduation and NCLEX-RN pass rates; MH nurse vacancy
      rates; and nurse retention rates after first employment.

PMID- 22142921
TI  - Academic partnerships to increase nursing education capacity: centralized faculty
      resource and clinical placement centers.
AB  - The North Texas Consortium of Professional Nursing Programs and Practice Partners
      is a regional academic partnership of nursing education and practice
      organizational leaders working together to share innovative ideas and best
      practices and to improve efficiencies that impact nursing education. The region's
      15 nursing schools produced 25% of the Texas graduates, or 1,782 graduates, in
      2008-2009. Yet, 3,522 graduates are needed in 2013-2014 to meet the projected
      north Texas demand. Barriers to increasing enrollment and graduation numbers were
      the lack of sufficient faculty to meet demand and insufficient numbers of
      clinical placement sites. To increase the capacity for graduating the numbers of
      nurses needed, the region developed a three-pronged plan to overcome each of
      these barriers: expansion of partnership members and development of a regional
      computerized clinical placement center and faculty resource center. The academic
      partnership expanded its members to include the 15 schools of nursing, more than
      50 hospitals, and the Dallas Fort Worth Hospital Council (DFWHC) Foundation for
      the purposes of governance of the two proposed computerized centers and strategic
      planning for increased capacity. The faculty resource center is a centralized,
      one-stop shop for those interested in teaching and those needing faculty. The
      Centralized Clinical Placement Center is expected to streamline the nursing
      student clinical placements process and monitor the numbers of students per site
      at a given time so as to ensure that placements are at capacity and that schools
      of nursing benefit fairly in placing students in specialty areas to meet course
      objectives.

PMID- 22142922
TI  - Transitioning associate degree in nursing students to the Bachelor of Science in
      nursing and beyond: a mandate for academic partnerships.
AB  - The Institute of Medicine recommendation for 80% of nurses to achieve a
      baccalaureate degree in nursing by 2020 becomes a major challenge in Texas with
      only 37.3% of nurses holding this degree in 2010 (Institute of Medicine, 2011).
      The challenge requires a 42.7% increase in the percentage of baccalaureate
      prepared nurses. Regionally, nurse educators together with nurse practice
      partners are seeking solutions to this challenge. One region in west Texas
      approached this challenge by first developing and launching a needs assessment
      for current associate degree nurses, nursing students, faculty, and nurse
      managers. The results of this needs assessment are presented in this article.
      Following institutional review board approval, three surveys were developed to
      capture the perceptions of students enrolled in Texas associate degree nursing
      (ADN) programs and their faculty regarding enrollment in a bachelor of science in
      nursing program. A similar survey was developed for chief nursing officers in
      acute care settings in west Texas. Respondents in all categories suggested that
      time, financial constraints, and perceived difficulty in completing needed
      prerequisite general education courses were barriers to RNs continuing their
      education. Because most of the respondents hoped to return to school within 5
      years, recruiting ADN graduates who have been out of school 5 years or less seems
      to be where schools of nursing should invest their recruitment efforts.

PMID- 22142923
TI  - A regional partnership to promote nursing instructor competence and confidence in
      simulation.
AB  - Clinical simulation is an innovative, research-based instructional strategy, and
      many faculty report not being adequately prepared to use this type of teaching
      strategy. Instructors in both academia and hospital staff development report
      reluctance to incorporate this new teaching methodology into the curriculum
      because they have negative attitudes about their own level of competence and
      confidence in using the simulators with students. Instructors clearly require
      training to help them understand the pedagogy, educational theory, and effective
      use of high-fidelity manikins. To promote simulation as a teaching strategy, a
      partnership was formed between academia (associate degree in nursing/bachelor of
      science in nursing) and staff development departments to train their instructors
      in an efficient, effective, and timely manner. This article describes a regional
      academic partnership between nursing programs and service partners in a 13-county
      region in the Texas Gulf Coast that used a train-the-trainer model and other
      activities to promote the use of simulation.

PMID- 22142924
TI  - Creating and sustaining academic-practice partnerships: lessons learned.
AB  - This article outlines how one community's academic-practice partnership evolved
      over time as it sought to address the community's needs for a qualified competent
      nursing workforce. Both organization and system changes were essential in the
      establishment of formal structures to address nursing workforce shortage needs.
      Both practice and education leaders were actively engaged in setting the
      strategic priorities at multiple system levels in the creation of these formal
      structures. We anticipate that the formation of these new formal structures will
      advance and sustain our academic-practice partnerships. Five key lessons were
      learned: (a) change is inevitable, (b) leadership matters at all levels, (c)
      succession planning is essential, (d) persistence toward established goals is
      necessary, and (e) relationships are the glue to sustain forward movement.

PMID- 22142925
TI  - Partnering to maximize simulation-based learning: nursing regional
      interdisciplinary simulation centers.
AB  - The Upper Rio Grande Texas Schools of Nursing Regional Partnership, which is
      composed of the University of Texas at El Paso School of Nursing, Texas Tech
      University Health Science Center School of Nursing at El Paso, and the El Paso
      Community College School of Nursing, received American Recovery and Reinvestment
      Act funding under the Texas Tech University Health Science Center's umbrella to
      establish four Nursing Regional Interdisciplinary Simulation Centers (NRISC) in
      2009. The NRISC were established as a partnership between the schools of nursing
      and four El Paso, TX, hospitals: Del Sol Medical Center, Sierra Medical Center,
      University Medical Center of El Paso, and Las Palmas Medical Center. This unique
      and innovative partnership had the following outcomes: (a) increased capacity to
      produce more nurses and (b) increased synergy among all the partners in relation
      to the use of simulation-based learning.

PMID- 22142926
TI  - Educational pipelines of nurses in Texas: promoting academic mobility through
      partnerships.
AB  - Texas, like many states across the nation, is struggling to position itself to
      achieve the Institute of Medicine (IOM) recommendations on the future of nursing.
      This article provides insights into the hurdles faced by Texas in achieving some
      of the IOM goals, particularly those related to a better educated nursing
      workforce. Only 9% of actively licensed nurses have pursued higher degrees,
      putting Texas below the national average. Currently, there is a gap between
      actual academic mobility and national recommendations to increase the numbers of
      baccalaureate- and doctorate-prepared nurses by 2020. The purpose of this study
      was to evaluate the educational pipeline in the state of Texas while suggesting
      partnerships as a solution to promote academic mobility. This cross-sectional
      study evaluated the academic mobility of four selected cohorts of nurses who have
      been in practice for 5 to 20 years. The findings revealed limited academic
      mobility compared with national benchmarks among all cohorts, regardless of basic
      degree and length in the profession. Educational pipelines for nurses need to be
      more dynamic in Texas than current trends reflect. Collaboration and partnerships
      between academics, clinicians, administrators, employers, and policy makers
      should be developed to address barriers that are deterring nurses from continuing
      their education.

PMID- 22142927
TI  - Building academic capacity through statewide partnerships.
AB  - In 2008, Texas was challenged by the Center to Champion Nursing in America, an
      initiative of the Robert Wood Johnson Foundation and AARP, to join a nationwide
      campaign for action to increase nursing education capacity. This article
      describes how one state created academic partnerships to achieve capacity
      building and strengthened relationships and commitments to invest in nursing
      education. Three year outcomes include a) the creation of a statewide team to
      address nursing education capacity, b) progress toward doubling the number of
      nursing graduates from the state's schools of nursing, c) strengthening and
      emphasizing retention efforts across the state, d) regionalization, including
      implementation of a $1 million grant and e) transitioning the statewide team to a
      broader focus and commitment to the Initiative on the Future of Nursing via the
      formation of a Regional Action Coalition.

PMID- 22142928
TI  - An analysis of partnership performance: the St. Johns Mercy Medical Center-Saint
      Louis University School of Nursing dedicated education unit project.
AB  - The purpose of this article is to analyze the St. Johns Mercy Medical Center
      (SJMMC)-Saint Louis University School of Nursing (SLUSON) dedicated education
      unit (DEU) project for partnership effectiveness. The DEU, an innovative and
      collaborative academic-service partnership, reconceptualizes the role of the
      faculty and staff nurse in the clinical educational process. In a DEU, the staff
      nurse provides the clinical instruction to the student, and the faculty member
      coaches the staff nurse on the teaching-learning process. Rather than explore the
      effectiveness of the DEU as an innovative clinical pedagogy, this article
      analyzes the relationship between the academic and service institutions for
      strategic effectiveness. The analysis is based on themes found across three
      successful and distinct academic partnerships and other evaluative models from
      business, government, and alliance research. The themes and models provide the
      frameworks needed to analyze the SJMMC-SLUSON academic-service partnership for
      structure, process, and outcomes. This analysis can serve as a guide for the
      development of academic-service partnership practices to facilitate successful,
      sustainable, and replicable partnerships that benefit both institutions.

PMID- 22142929
TI  - Creativity and connections: the future of nursing education and practice: the
      Massachusetts Initiative.
AB  - Education and practice partnerships are key to effective academic program design
      and implementation in a time of decreasing supply and increasing demands on the
      nursing profession. An integrated education/practice competency model can
      positively impact patient safety, improve patient care, increase retention, and
      ensure a sufficient and competent nursing workforce, which is paramount to
      survival of the health care system. Through the contributions of nursing leaders
      from the broad spectrum of nursing and industry organizations within the state,
      the Massachusetts Nurse of the Future project developed a competency-based
      framework for the future design of nursing educational programs to meet current
      and future practice needs. The Massachusetts Nurse of the Future Nursing Core
      Competencies((c)) expand on the Institute of Medicine's core competencies for all
      health care professionals and the Quality and Safety Education for Nurses
      competencies for quality and safety to define the expectations for all
      professional nurses of the future. The Massachusetts Nurse of the Future Nursing
      Core Competencies define the knowledge, attitude, and skills required as the
      minimal expectations for initial nursing practice following completion of a
      prelicensure professional nursing education program. These competencies are now
      being integrated into new models for seamless, coordinated nursing curriculum and
      transition into practice within the state and beyond.

PMID- 22142930
TI  - Expanding an academic-practice partnership.
AB  - This article describes an example of an academic-practice partnership between a
      university-based school of nursing and a multihospital health system that is
      based on our common past and has grown significantly as we have embraced
      opportunities for collaboration and innovation. Our primary goals were to enhance
      the education of students and staff and, ultimately, improve patient care
      outcomes. These goals were closely aligned with the recommendations of the
      Institute of Medicine's taskforce on the Future of Nursing for seamless academic
      progression and improved practice environments. The expansion of the partnership
      centered on three separate initiatives: education, health information technology,
      and practice involvement.

PMID- 22142931
TI  - Lessons learned from a history of perseverance and innovation in academic
      practice partnerships.
AB  - Nurse leaders today are faced with a pressing concern to reevaluate established
      community resources and models for academic-practice partnerships that have been
      used in the preparation of new and advanced practice nurses. Nursing reform in
      education and practice is not achieved as a simple series of decisions in the
      present moment with future direction as its object. It is a process in which the
      outcome is ultimately evaluated within the context of history. Academic-practice
      partnerships are part of a nursing heritage that has persevered for hundreds of
      years. This article is a brief synopsis of examples from the historical records
      that evidence the lessons learned from the experiences of nurses who have formed
      innovative academic-practice partnerships with religious communities, medical
      colleges and physicians, government, hospitals, institutions of higher learning,
      and nursing organizations.

PMID- 22142932
TI  - A regional academic partnership for the early identification and retention of at
      risk nursing students.
AB  - In a 2006 Texas Higher Education Coordinating Board report (Increasing RN
      Graduates in Texas: A Report to the 79th Legislature), nursing programs in Texas
      were challenged to increase the number of graduates to deal with the nursing
      shortage. This article describes the East Texas region's efforts to identify and
      intervene in the nursing student attrition rates of participating partners
      nursing programs. The primary purpose of this study was to identify and intervene
      with students at risk for attrition. Nine nursing programs participated in the
      study. METHODS: Online surveys were used to assess variables associated with
      attrition. Online interventions and an intensive test review protocol were used
      as intervention methods. RESULTS: Across the nine nursing programs, 898 students
      participated in the study. Regression and categorical data analysis revealed that
      lack of reading comprehension was the best predictor of a student being off track
      or out of a nursing program (P < .0001). Two other highly predictive variables of
      attrition were entrance examination composite scores (P = .0271) and a student's
      grades in anatomy and physiology (P = .005). Grant intervention protocols were
      effective in reducing the attrition rate (P = .0002) between students who
      participated during the grant period and those prior to implementation of the
      grant.

PMID- 22142933
TI  - Academic service partnerships: organizational efficiency and efficacy between
      organizations.
AB  - Two leading nursing organizations, the Greater Kansas City Area Collegiate Nurse
      Educators and the Kansas City Area Nurse Executives, represent the Kansas City
      metropolitan area nursing programs and area employers. These two organizations
      have been engaged in collaborative workforce planning and strategy development
      around key nursing issues for over 25 years. This model of collaboration is
      unique in that the partnership is between organizations representing 17 nursing
      programs and 28 hospitals. The collaborative partnership has enhanced
      organizational efficiency and efficacy between the groups, which has directly
      benefited the organizational members. Most importantly, it has had a
      transformative impact on both nursing education and professional practice in the
      Kansas City metropolitan area. This article describes the evolution of the
      partnership and the collaborative work that has led to the accomplishment of
      mutual goals.

PMID- 22142934
TI  - Hallmarks of best practice in academic-service partnerships in nursing: lessons
      learned from San Antonio.
AB  - TOPIC INVESTIGATED: The objectives of this project were to (a) identify best
      practice in academic-practice partnerships; (b) identify the needs and/or desire
      for greater collaboration and partnership between the University of Texas Health
      Science Center San Antonio School of Nursing (SON) and key stakeholders in San
      Antonio, TX; and (c) guide the work of a national task force. METHODS: One-on-one
      open-ended interviews were conducted with deans of nursing and vice presidents of
      patient care services at the six major health systems in San Antonio. Focus
      groups were also conducted with individuals who included chief nursing officers,
      vice presidents of a hospital, nurse managers, clinical educators, and clinical
      researchers. Data were analyzed using content analysis. RESULTS: Seventy-two
      individuals participated, and all expressed a desire for greater partnership with
      the SON. All identified characteristics of best practice in academic-service
      partnerships and the value or benefits of such partnerships. All participants
      believed that partnerships between academic and service were critical to the
      advancement of quality patient care. CONCLUSIONS: There has been limited research
      published to date that explicates the complexities of developing and sustaining
      partnerships between academia and practice. This article highlights preliminary
      findings on best practices in academic-service partnerships.

PMID- 22142935
TI  - The New Jersey Nursing Initiative: building sustainable collaboration.
AB  - The New Jersey Nursing Initiative was publically launched in 2009 as a 5-year,
      $22 million program of the Robert Wood Johnson Foundation based at the New Jersey
      Chamber of Commerce Foundation. It was reauthorized in 2011 through 2016 for an
      additional $8.5 million. The initiative includes a faculty preparation program
      and strategic tracks of work focusing on building education capacity, increasing
      current faculty capacity, making nurse faculty a preferred career, leading policy
      initiatives, creating sustainable funding in support of nursing education, and
      ultimately, building local, regional, and statewide collaborative networks. The
      tagline, "So a Nurse will be there for You," emphasizes both the reality of an
      aging nursing workforce needing replacement and the expected health care
      transformation that will result in the need for new knowledge and skills in the
      future nursing workforce. The purpose of this article was to describe the New
      Jersey Nursing Initiative, emphasizing the partnerships that have resulted from
      the project to date.

PMID- 22142936
TI  - Psychometric properties of the Revised Illness Perception Questionnaire: factor
      structure and reliability among African-origin populations with type 2 diabetes.
AB  - BACKGROUND: The Revised Illness Perception Questionnaire (IPQ-R) has been used
      extensively to measure illness perceptions of several patient populations.
      However, the instrument was developed using participants of mainly European
      origin. The reliability and validity of the IPQ-R may therefore need to be
      established before use among populations of different ethnic and cultural
      origins. OBJECTIVES: This study investigated the factor structure and internal
      consistency reliability of the IPQ-R in African-origin patients with type 2
      diabetes. METHODS: In this cross-sectional study, 221 adults of African descent
      with type 2 diabetes completed the IPQ-R. Participants were recruited from
      patients attending diabetes and retinal screening clinics in the London boroughs
      of Brent and Hackney. Confirmatory Factor Analysis based on the covariance matrix
      was used to determine factorial validity for the Timeline-acute/chronic,
      Consequences, Personal control, Treatment control, Illness coherence, Timeline
      cyclical, Emotional representation and three causal subscales of the IPQ-R.
      Composite internal consistency reliability for individual subscales was
      determined using Cronbach's alpha coefficients. RESULTS: After eliminating three
      items and re-specifying six error covariances associated with large standardised
      residuals and low factor loadings, the hypothesised model adequately explained
      the covariance of African and Caribbean patients' responses to items of the IPQ
      R. Also, composite reliability coefficients of all measured subscales were
      acceptable and inter-correlations between subscales were in line with those
      reported from other population groups. CONCLUSIONS: The findings in this study
      suggest that although the IPQ-R may be valid and reliable across cultures,
      investigators may need to modify (e.g. by rewording) some of its items taking
      into account any linguistic origins of their populations of study. Further
      evaluation of the IPQ-R (including the identity subscale) in larger samples of
      African-origin populations is also recommended.

PMID- 22142937
TI  - Non-extractable proanthocyanidins from grapes are a source of bioavailable
      (epi)catechin and derived metabolites in rats.
AB  - The non-extractable fraction of many fruit and vegetables contains putatively
      bioactive polyphenolic compounds that, in most cases, have not been well
      characterised structurally. Non-extractable proanthocyanidins (NEPA) of a
      polymeric nature are part of the dietary fibre fraction of food. Using liquid
      chromatography coupled to a mass spectrometer equipped with an electrospray
      ionisation chamber and a triple quadrupole mass analyser for tandem analysis
      (HPLC-ESI-QqQ-MS/MS) techniques, we examine the phenolic metabolites present in
      urine and faeces from rats 24 h after ingestion of an NEPA-rich fraction. We show
      that NEPA are partially depolymerised during their transit along the intestinal
      tract, as evidenced by the presence of (epi)catechin (EC) monomers and dimers in
      faeces and phase II conjugates of EC in urine. Moreover, NEPA are further
      metabolised by the intestinal microbiota into smaller metabolites including
      phenolic acids that are present in urine as both free phenolics and conjugates
      with glucuronate or sulphate moieties. For the first time, we report evidence
      that NEPA behave in vivo as a source of phenolics that are released progressively
      and deliver phenolic species that come into contact with the intestinal walls and
      are bioavailable for at least 24 h after ingestion.

PMID- 22142938
TI  - Adherence to dietary recommendations and risk of esophageal squamous cell
      carcinoma: a case-control study in Iran.
AB  - BACKGROUND/AIM: The Dietary Guidelines for Americans Adherence Index (DGAI) 2005
      was developed to assess the contribution of dietary patterns to chronic disease
      risk. The objective of this study was to evaluate the association of dietary
      patterns as measured by the DGAI 2005 with the esophageal squamous cell carcinoma
      (ESCC) risk in Iran. METHODS: This case-control study was conducted on 50 ESCC
      cases and 100 hospital controls aged 40-75 years. Participants were interviewed
      using validated food frequency questionnaires and the DGAI score was calculated
      subsequently. RESULTS: Generally, the mean DGAI 2005 score for this population
      was low (9.54 +/- 1.79) and the control group scored significantly higher
      compared to the ESCC cases (p < 0.001). Being in the highest tertile of DGAI
      scores reduced the risk of ESCC by 31%. Consumption of salty, peppery, and sour
      foods in combination increased the ESCC risk by 7.23%, followed by consumption of
      fried/barbecued meals (OR 3.79; 95% CI 1.10-5.44; p < 0.001) and high-temperature
      food/beverages (OR 3.68; 95% CI 1.20-8.99; p < 0.001). CONCLUSIONS: Consumption
      of a diet in accordance with dietary recommendations was associated with a lower
      risk of ESCC. Preventive strategies to reduce the ESCC risk in high-risk regions
      of the world should focus on overall dietary patterns and dietary habits in order
      to be effective.

PMID- 22142939
TI  - Optimization of ultrasound-assisted extraction (UAE) of flavonoids compounds (FC)
      from hawthorn seed (HS).
AB  - Hawthorn seed (HS), an important by-product of the Hawthorn industry, is rich in
      potentially health-promoting flavonoids compounds. In this paper, the ultrasound
      assisted extraction (UAE) of FC from HS was investigated. Important variables and
      their levels were obtained using Plackett-Burman (PB) design and Box-Behnken (BB)
      design. A mathematical model was developed to show the effects of each variable
      and their combinatorial interactions on extraction yield of FC. A high
      coefficient of determination (R(2) = 91.26%) indicated good agreement between the
      experimental and predicted values of FC yield. The optimum levels of these
      significant parameters were determined using response surface methodology (RSM),
      which revealed these as follows: ultrasound temperature 65  degrees C, ultrasonic
      time 37 min, extraction temperature 91  degrees C, extraction time 1.5h, solid
      liquid ratio of 1:18, and 72% ethanol. Under the optimum condition, the UAE rate
      of FC was up to 91.7%, and the yield of FC was 16.45 +/- 0.02 mg/g (P<0.05) that
      was 1.32-fold the yield of conventional reflux extraction (CRE).

PMID- 22142940
TI  - Strong correlation of high EBNA-1-IgG levels with edematous attacks involving
      upper airway mucosa in hereditary angioedema due to C1-inhibitor deficiency.
AB  - Elevated level of IgG-type antibodies against Type 1 nuclear antigen (anti-EBNA-1
      IgG) of the Epstein-Barr virus is a strong risk factor for certain autoimmune
      diseases. We measured anti-EBNA-1 IgG titers in 107 patients with hereditary
      angioedema due to C1-inhibitor deficiency (HAE-C1-INH). In the sera from 33
      longitudinally tested patients, we found a very strong correlation (R>0.75,
      p=0.0005) between anti-EBNA-1-IgG titers measured in 2004 and 2010, respectively.
      High (>200 U/ml) anti-EBNA-1 levels were strongly correlated with the frequency
      of upper airway attacks (p=0.003) and the dose requirement of C1-inhibitor
      concentrate (p=0.008), while no significant association with the frequency of
      subcutaneous and abdominal attacks was found. These novel findings indicate that
      the underlying/triggering mechanisms of upper airway attacks in HAE-C1-INH may
      differ from that of other types of attacks and measurement of the anti-EBNA-1 IgG
      levels may be suitable for the prediction of upper airway attacks and C1
      inhibitor concentrate requirement in HAE-C1-INH patients.

PMID- 22142942
TI  - Use of the internet for health information: United States, 2009.
AB  - Research has shown that 74% of all U.S. adults use the Internet, and 61% have
      looked for health or medical information on the Internet. Additionally, 49% have
      accessed a website that provides information about a specific medical condition
      or problem. In 2009, the National Health Interview Survey (NHIS) became the first
      nationally representative household survey to collect data on the use of health
      information technology when the U.S. Department of Health and Human Services,
      Office of the Assistant Secretary for Planning and Evaluation sponsored 10
      questions that asked about use of the Internet to look up health information,
      refill a prescription, schedule a medical appointment, learn about health topics
      in online chat groups, and e-mail a health care provider. This report provides
      estimates, using 2009 NHIS data, about adult use of the Internet for health
      information in the past 12 months, by selected sociodemographic characteristics.

PMID- 22142941
TI  - Interleukin-4 and interleukin-13 inhibit the expression of leukemia inhibitory
      factor and interleukin-11 in fibroblasts.
AB  - Cytokines produced by inflammatory or resident mesenchymal cells play important
      modulatory roles in the pathogenesis of inflammation induced bone loss. In the
      present study, the effects of IL-4 and IL-13 on the expression of three
      osteotropic cytokines in the IL-6 family expressed in human gingival fibroblasts
      were studied. IL-4Ralpha and IL-13Ralpha1 mRNA were constitutively expressed in
      human gingival fibroblasts. The inflammatory cytokines IL-1beta and TNF-alpha
      increased expression of IL-6, LIF, and IL-11 mRNA and protein in the gingival
      fibroblasts. Addition of IL-4 or IL-13 had no effect on IL-6 expression, but
      significantly inhibited LIF and IL-11 mRNA and protein stimulated by IL-1beta and
      TNF-alpha. No involvement of NF-kappaB or STAT1 was observed in the inhibition.
      STAT6 was phosphorylated at Y641 by treatment with IL-4 and knockdown of STAT6
      with siRNA decreased the inhibition of IL-11 and LIF expression by IL-4 in IL
      1beta and TNF-alpha stimulated cells. This study suggests that activation of
      STAT6 by IL-4 and IL-13, through type 2 IL-4 receptors, inhibits production of IL
      11 and LIF stimulated by IL-1beta and TNF-alpha in human gingival fibroblasts. A
      negative modulatory role of IL-4 and IL-13 in osteotropic cytokine production
      could be a mechanism playing an important inhibitory role in inflammation induced
      periodontitis.

PMID- 22142943
TI  - Expression profiling, gene silencing and transcriptional networking of metzincin
      metalloproteases in the cattle tick, Rhipicephalus (Boophilus) microplus.
AB  - Tick proteins functioning in vital physiological processes such as blood meal
      uptake, digestion and reproduction are potential targets for anti-tick vaccines,
      since vaccination could inhibit these essential functions and ultimately affect
      tick survival. In this study we identified metzincin metalloproteases from
      Rhipicephalus microplus as potential vaccine candidates since they are implicated
      as essential to blood-cavity formation, bloodmeal digestion and reproduction in
      ixodid ticks. Eight transcripts encoding proteins that contain the characteristic
      metzincin zinc-binding motif HEXXHXXG/NXXH/D and a unique methionine containing
      "methionine-turn" were identified from native and in-house assembled R. microplus
      expressed sequence tag (EST) databases. These were representative of five
      reprolysin-like and three astacin-like metzincin metalloproteases. Reverse
      transcription-PCR analysis indicated that the reprolysins were most abundantly
      expressed in the salivary glands, whereas the astacins were most abundant in the
      midgut and ovaries. In vivo gene silencing was performed to assess a possible
      phenotype of these metalloproteases during adult female R. microplus blood
      feeding and reproduction. RNA interference (RNAi) against two of the reprolysins
      and one of the astacins significantly affected the average egg weight and
      oviposition rate. Evidently, this reverse genetic approach enabled the evaluation
      of the overall vital impact of tick proteins. Finally, integrated real time-PCR
      studies also revealed an extensive cross organ network between the R. microplus
      metzincin transcripts, supporting the use of a combinatorial metzincin-based anti
      R. microplus vaccine.

PMID- 22142944
TI  - Ixodes eldaricus Djaparidze, 1950 (Ixodidae) on migrating birds--reported first
      time in Poland.
AB  - During the ornithological "Operation Baltic" on the Hel Peninsula (the Baltic Sea
      coast in Poland) the first case of transfer to Poland of ticks of the species
      Ixodes eldaricus Djaparidze, 1950, on Prunella modularis (one female tick) and
      Erithacus rubecula (two males and one female tick). P. modularis and E. rubecula
      have not previously been recorded among the hosts of this tick species. Although
      the natural populations of I. eldaricus are very distant from Poland, it should
      be taken into account that this and other species of ticks may be transferred
      every year on migratory birds in the southern part of Central Europe and further
      north. Each case requires faunistic observation and epidemiological and
      morphological studies to exclude diagnostic confusion between very similar
      morphology in specimens of the genus Ixodes.

PMID- 22142945
TI  - Using the ResearchEHR platform to facilitate the practical application of the EHR
      standards.
AB  - Possibly the most important requirement to support co-operative work among health
      professionals and institutions is the ability of sharing EHRs in a meaningful
      way, and it is widely acknowledged that standardization of data and concepts is a
      prerequisite to achieve semantic interoperability in any domain. Different
      international organizations are working on the definition of EHR architectures
      but the lack of tools that implement them hinders their broad adoption. In this
      paper we present ResearchEHR, a software platform whose objective is to
      facilitate the practical application of EHR standards as a way of reaching the
      desired semantic interoperability. This platform is not only suitable for
      developing new systems but also for increasing the standardization of existing
      ones. The work reported here describes how the platform allows for the edition,
      validation, and search of archetypes, converts legacy data into normalized,
      archetypes extracts, is able to generate applications from archetypes and
      finally, transforms archetypes and data extracts into other EHR standards. We
      also include in this paper how ResearchEHR has made possible the application of
      the CEN/ISO 13606 standard in a real environment and the lessons learnt with this
      experience.

PMID- 22142946
TI  - Selected papers from the 2011 Summit on Translational Bioinformatics.

PMID- 22142947
TI  - In search of common ground in handoff documentation in an Intensive Care Unit.
AB  - OBJECTIVE: Handoff is an intra-disciplinary process, yet the flow of critical
      handoff information spans multiple disciplines. Understanding this information
      flow is important for the development of computer-based tools that supports the
      communication and coordination of patient care in a multi-disciplinary and highly
      specialized critical care setting. We aimed to understand the structure,
      functionality, and content of nurses' and physicians' handoff artifacts. DESIGN:
      We analyzed 22 nurses' and physicians' handoff artifacts from a Cardiothoracic
      Intensive Care Unit (CTICU) at a large urban medical center. We combined artifact
      analysis with semantic coding based on our published Interdisciplinary Handoff
      Information Coding (IHIC) framework for a novel two-step data analysis approach.
      RESULTS: We found a high degree of structure and overlap in the content of
      nursing and physician artifacts. Our findings demonstrated a non-technical, yet
      sophisticated, system with a high degree of structure for the organization and
      communication of patient data that functions to coordinate the work of multiple
      disciplines in a highly specialized unit of patient care. LIMITATIONS: This study
      took place in one CTICU. Further work is needed to determine the generalizability
      of the results. CONCLUSIONS: Our findings indicate that the development of semi
      structured patient-centered interdisciplinary handoff tools with discipline
      specific views customized for specialty settings may effectively support handoff
      communication and patient safety.

PMID- 22142948
TI  - Mapping Partners Master Drug Dictionary to RxNorm using an NLP-based approach.
AB  - OBJECTIVE: To develop an automated method based on natural language processing
      (NLP) to facilitate the creation and maintenance of a mapping between RxNorm and
      a local medication terminology for interoperability and meaningful use purposes.
      METHODS: We mapped 5961 terms from Partners Master Drug Dictionary (MDD) and 99
      of the top prescribed medications to RxNorm. The mapping was conducted at both
      term and concept levels using an NLP tool, called MTERMS, followed by a manual
      review conducted by domain experts who created a gold standard mapping. The gold
      standard was used to assess the overall mapping between MDD and RxNorm and
      evaluate the performance of MTERMS. RESULTS: Overall, 74.7% of MDD terms and
      82.8% of the top 99 terms had an exact semantic match to RxNorm. Compared to the
      gold standard, MTERMS achieved a precision of 99.8% and a recall of 73.9% when
      mapping all MDD terms, and a precision of 100% and a recall of 72.6% when mapping
      the top prescribed medications. CONCLUSION: The challenges and gaps in mapping
      MDD to RxNorm are mainly due to unique user or application requirements for
      representing drug concepts and the different modeling approaches inherent in the
      two terminologies. An automated approach based on NLP followed by human expert
      review is an efficient and feasible way for conducting dynamic mapping.

PMID- 22142949
TI  - An ontology for clinical questions about the contents of patient notes.
AB  - OBJECTIVE: Many studies have been completed on question classification in the
      open domain, however only limited work focuses on the medical domain. As well, to
      the best of our knowledge, most of these medical question classifications were
      designed for literature based question and answering systems. This paper focuses
      on a new direction, which is to design a novel question processing and
      classification model for answering clinical questions applied to electronic
      patient notes. METHODS: There are four main steps in the work. Firstly, a
      relatively large set of clinical questions was collected from staff in an
      Intensive Care Unit. Then, a clinical question taxonomy was designed for question
      and answering purposes. Subsequently an annotation guideline was created and used
      to annotate the question set. Finally, a multilayer classification model was
      built to classify the clinical questions. RESULTS: Through the initial
      classification experiments, we realized that the general features cannot
      contribute to high performance of a minimum classifier (a small data set with
      multiple classes). Thus, an automatic knowledge discovery and knowledge reuse
      process was designed to boost the performance by extracting and expanding the
      specific features of the questions. In the evaluation, the results show around
      90% accuracy can be achieved in the answerable subclass classification and
      generic question templates classification. On the other hand, the machine
      learning method does not perform well at identifying the category of unanswerable
      questions, due to the asymmetric distribution. CONCLUSIONS: In this paper, a
      comprehensive study on clinical questions has been completed. A major outcome of
      this work is the multilayer classification model. It serves as a major component
      of a patient records based clinical question and answering system as our studies
      continue. As well, the question collections can be reused by the research
      community to improve the efficiency of their own question and answering systems.

PMID- 22142950
TI  - Interdental distraction osteogenesis for the management of alveolar clefts:
      archwise distraction.
AB  - Bone grafting is a successful protocol for cleft repair but it is very
      challenging to close large gaps using local gingival tissue. In the last decade,
      interdental distraction osteogenesis has been introduced as a successful
      treatment protocol for repairing such large clefts. In this article a new method
      for closing the alveolar cleft is introduced and one case is presented. A tooth
      supported distractor which was specially designed to be inserted on to the main
      arch wire was used for the distraction. The aim was to distract the tooth
      segments through the curve of the dental arch and achieve complete closure of the
      gaps. The distractor introduced had several advantages: it is simple to apply,
      activate and remove; there is no need for a second operation; it is an outpatient
      procedure. In the case reported, a very large gap was successfully closed using
      this protocol whilst maintaining the ideal arch form and generating new bone
      behind the distracted segments.

PMID- 22142951
TI  - Internally vs. externally triggered movements in patients with major depression.
AB  - BACKGROUND: Psychomotor retardation is a prominent clinical feature of major
      depression. While several studies investigated these deficits, differences
      between internally and externally triggered response selection and initiation are
      less well understood. In the current study, we delineate internally vs.
      externally driven response selection and initiation in depression and their
      relation to basic psychomotor functioning. METHODS: 20 inpatients diagnosed with
      a (unipolar) major depression and 20 closely matched healthy controls performed a
      computerized motor paradigm assessing differences between internally and
      externally cued movements. Psychomotor performance and basic memory functions
      were assessed using a neuropsychological test-battery. To examine within group
      homogeneity a multivariate clustering approach was applied. RESULTS: Patients
      featured a global slowing of internally and externally cued response selection
      compared to controls, as well as impairments in basic psychomotor functioning.
      Yet, basic motor speed was preserved. Furthermore, patients were more severely
      impaired when movements involved internal response selection. The data-driven
      clustering revealed two patient subgroups, which both showed psychomotor
      disturbances, while only one featured slowing of response selection.
      INTERPRETATION: The results suggest a differential rather than a global
      psychomotor slowing in major depression with specific impairments of visuospatial
      and attentional processing as cognitive aspects of psychomotor functioning. As
      found for depression, in Parkinson's disease internally cued movements are more
      severely affected than externally cued reactions. Both may therefore be caused by
      dopaminergic deregulation due to frontostriatal deficits. Finally, multivariate
      clustering of behavioral data may be a promising future approach to identify
      subtypes of psychomotor or cognitive disturbances in different patient
      populations.

PMID- 22142952
TI  - Personality traits and the R668Q polymorphism located in the MMP-9 gene.
AB  - Matrix metalloproteinases (MMPs) are enzymes involved in degradation of proteins
      in the extracellular matrix and have been shown to contribute to
      neuroinflammation by several mechanisms such as blood-brain barrier breakdown.
      Among the MMPs, MMP-9 (gelatinase B) has been suggested to be of relevance also
      for synaptic and behavioural plasticity. In order to explore the role of MMP-9
      for mental functions a polymorphism in MMP-9 was analysed with respect to
      personality traits. The two studied populations consisted of women and men,
      respectively, both recruited from the population registry and assessed by means
      of the Karolinska Scales of Personality. The non-synonymous single nucleotide
      polymorphism (R668Q, rs17577) studied is located in the coding region of MMP-9
      and is believed to affect the activity of the enzyme. The present study found
      that an amino acid change from arginine (R) to glutamine (Q) was associated with
      higher scores of the personality trait inhibition of aggression in the female
      population whilst this substitution was associated with higher scores of verbal
      aggression and irritability in men. These findings give support for an influence
      of MMP-9 on mental functions.

PMID- 22142953
TI  - Learning-performance distinction and memory processes for motor skills: a focused
      review and perspective.
AB  - Behavioral research in cognitive psychology provides evidence for an important
      distinction between immediate performance that accompanies practice and long-term
      performance that reflects the relative permanence in the capability for the
      practiced skill (i.e. learning). This learning-performance distinction is
      strikingly evident when challenging practice conditions may impair practice
      performance, but enhance long-term retention of motor skills. A review of motor
      learning studies with a specific focus on comparing differences in performance
      between that at the end of practice and at delayed retention suggests that the
      delayed retention or transfer performance is a better indicator of motor learning
      than the performance at (or end of) practice. This provides objective evidence
      for the learning-performance distinction. This behavioral evidence coupled with
      an understanding of the motor memory processes of encoding, consolidation and
      retrieval may provide insight into the putative mechanism that implements the
      learning-performance distinction. Here, we propose a simplistic empirically-based
      framework--motor behavior-memory framework--that integrates the temporal
      evolution of motor memory processes with the time course of practice and delayed
      retention frequently used in behavioral motor learning paradigms. In the context
      of the proposed framework, recent research has used noninvasive brain stimulation
      to decipher the role of each motor memory process, and specific cortical brain
      regions engaged in motor performance and learning. Such findings provide
      beginning insights into the relationship between the time course of practice
      induced performance changes and motor memory processes. This in turn has
      promising implications for future research and practical applications.

PMID- 22142954
TI  - Subgingival biofilm structure.
AB  - Periodontitis is an inflammatory disease of the oral cavity initiated by a
      microbial biofilm (or 'dental plaque'). Subgingival biofilms in periodontal
      pockets are not easily analyzed without the loss of structural integrity. These
      subgingival plaques are structured communities of microorganisms with great
      phylogenetic diversity embedded in a self-produced extracellular polymeric
      matrix. For almost three decades, knowledge of the structure of plaque located
      below the gingival margin has been limited to landmark studies from the 1970s
      that were unaware of the breadth of microbial diversity we appreciate now. Only
      recently has technical progress - combining histology, confocal scanning
      fluorescent microscopy and fluorescent in situ hybridization to localize the most
      abundant species from different phyla and species associated with periodontitis -
      provided new insights into the architecture of subgingival biofilms. This review
      focuses on the structure and composition of subgingival biofilms and discusses
      current knowledge on the nature of the extracellular matrix. We describe further
      structural aspects of 'subgingival' biofilms produced in vitro that are gaining
      considerable interest as we search for models to investigate biofilm development,
      resistance to antibiotics, extracellular polymeric matrix composition and
      function, and reciprocal host-cell-to-biofilm interactions.

PMID- 22142955
TI  - Microbial diversity and interactions in subgingival biofilm communities.
AB  - The human subgingival environment is a complex environmental niche where
      microorganisms from the three domains of life meet to form diverse biofilm
      communities that exist in close proximity to the host. Bacteria constitute the
      most abundant, diverse and ultimately well-studied component of these communities
      with about 500 bacterial taxa reported to occur in this niche. Cultivation and
      molecular approaches are revealing the breadth and depth of subgingival biofilm
      diversity as part of an effort to understand the subgingival microbiome, the
      collection of microorganisms that inhabit the gingival crevices. Although these
      investigations are constructing a pretty detailed taxonomical census of
      subgingival microbial communities, including inter-subject and temporal
      variability in community structure, as well as differences according to
      periodontal health status, we are still at the front steps in terms of
      understanding community function. Clinical studies that evaluate community
      structure need to be coupled with biologically relevant models that allow
      evaluation of the ecological determinants of subgingival biofilm maturation.
      Functional characteristics of subgingival biofilm communities that still need to
      be clarified include main metabolic processes that support microbial communities,
      identification of keystone species, microbial interactions and signaling events
      that lead to community maturation and the relationship of different communities
      with the host. This manuscript presents a summary of our current understanding of
      subgingival microbial diversity and an overview of experimental models used to
      dissect the functional characteristics of subgingival communities. Future
      coupling of 'omics'-based approaches with such models will facilitate a better
      understanding of subgingival ecology opening opportunities for community
      manipulation.

PMID- 22142956
TI  - Innate cellular responses to the periodontal biofilm.
AB  - This chapter addresses the host responses to the microbial biofilm that
      constitutes the subgingival dental plaque. The host response to infection draws
      upon the innate, inflammatory and adaptive immune systems, whose role is to
      provide the appropriate response to the offending microorganisms. In some cases,
      this will be little or no response when encountering 'commensals', and in other
      cases a gradated response depending very much on the host's own determination of
      the pathogenic nature of the microbial insult: and herein lies the root of
      variation in host responses that govern individual susceptibility. In some
      individuals and with some bacteria this will be an innate-only response, others
      will need to invoke the inflammatory response, and yet others will require the
      adaptive immune response - be it cellular, humoral or both - to reduce or remove
      the challenge from the microbes. Of course these responses would be somewhat
      easier to predict with a single pathogen challenge, and become infinitely more
      complex as the biofilm increases in complexity. Oral infections, in particular
      gingival inflammation, originate from not just one but many microorganisms. This
      polymicrobial infection may result in chronic inflammation, which may lead to
      tissue destruction, as evident in chronic periodontitis. Although many organisms
      are present in the subgingival biofilm, interestingly, the putative pathogens
      associated with gingivitis and periodontitis may comprise very small fractions of
      the total biomass. An understanding of the interaction of structural and
      defensive host cells with the biofilm is pivotal to understanding periodontal
      disease etiology and to developing tailored therapeutics. Thus, this chapter
      addresses the main structural cells, i.e. epithelial cells, exposed to the
      biofilm.

PMID- 22142959
TI  - Modern approaches to non-surgical biofilm management.
AB  - The subgingival dental plaque is a microbial biofilm consisting of highly
      variable bacterial microcolonies embedded within a self-produced matrix of
      extracellular polymeric substance. In contrast to microorganisms growing in a
      planktonic state, the inhabitants of a biofilm are effectively protected within
      this dense structure from host defense mechanisms and from therapeutic agents,
      including antimicrobials. The mechanical removal of the microbial biofilm and the
      establishment of meticulous plaque control measures comprise the key elements for
      the success of non-surgical periodontal treatment. Ultrasonic devices are
      effective in disrupting the biofilm, and carefully remove soft and hard deposits
      from a root surface with minimal trauma to the tooth structure. Controversies and
      modern trends in non-surgical periodontal therapy - such as quadrant-wise
      treatment modalities versus full-mouth approaches, hand-versus power-driven
      instrumentation, and the time frame of non-surgical periodontal therapy - are
      discussed here in depth in order to provide an insight into modern approaches to
      non-surgical biofilm management. Clinical, microbiological and immunological
      findings following different treatment protocols, in addition to cost-effective
      benefits of these clinical modalities, are discussed.

PMID- 22142957
TI  - Neutrophils in periodontal inflammation.
AB  - Neutrophils (also called polymorphonuclear leukocytes) are the most abundant
      leukocytes whose primary purpose as anti-microbial professional phagocytes is to
      kill extracellular pathogens. Neutrophils and macrophages are phagocytic cell
      types that along with other cells effectively link the innate and adaptive arms
      of the immune response, and help promote inflammatory resolution and tissue
      healing. Found extensively within the gingival crevice and epithelium,
      neutrophils are considered the key protective cell type in the periodontal
      tissues. Histopathology of periodontal lesions indicates that neutrophils form a
      'wall' between the junctional epithelium and the pathogen-rich dental plaque
      which functions as a robust anti-microbial secretory structure and as a unified
      phagocytic apparatus. However, neutrophil protection is not without cost and is
      always considered a two-edged sword in that overactivity of neutrophils can cause
      tissue damage and prolong the extent and severity of inflammatory periodontal
      diseases. This review will cover the innate and inflammatory functions of
      neutrophils, and describe the importance and utility of neutrophils to the host
      response and the integrity of the periodontium in health and disease.

PMID- 22142958
TI  - Antimicrobial peptides in periodontal innate defense.
AB  - The development of oral biofilms and the host response to biofilm bacteria and
      their toxins are important factors in the development of periodontal disease. An
      early component of the host response is the secretion of antimicrobial proteins
      and peptides (AMPs) by salivary glands, oral epithelial cells and neutrophils.
      Over 45 AMPs have been identified in the oral cavity. All are found in saliva and
      several are also present in gingival crevicular fluid. Of these, 13 are up
      regulated in periodontal disease while 11 are downregulated. However, the
      concentrations of most AMPs found in oral fluids are below the effective in vitro
      concentrations, suggesting that local concentrations must be higher for effect or
      that additional biological functions are important in the oral cavity. Thus, in
      addition to direct antibacterial activity (e.g. bactericidal activity, bacterial
      agglutination), AMPs may affect the course of periodontal disease by inactivating
      bacterial or host proteases (e.g. secretory leukoprotease inhibitor) or bind
      bacterial toxins, including lipopolysaccharides (e.g. LL-37). Several AMPs (e.g.
      defensins) also act as immune system alarmins, i.e. endogenous mediators that
      recruit and activate antigen-presenting cells to enhance innate and adaptive
      immune responses. The differential regulation of AMP expression in periodontal
      disease suggests that AMP panels, including up- and downregulated proteins, can
      be used in oral fluid diagnosis of periodontal disease and to monitor treatment
      outcome.

PMID- 22142961
TI  - Antimicrobial advances in treating periodontal diseases.
AB  - Antibiotics are generally an efficient means of treating bacterial infections,
      and therefore are an obvious candidate in the treatment of periodontal diseases.
      Systemically and locally administered antimicrobial agents of all kinds have been
      evaluated in multiple clinical trials. The vast majority of studies have tested
      antibiotics as adjuncts to non-surgical debridement. No regime has demonstrated
      superiority over systemically administered amoxicillin and metronidazole in the
      treatment of any clinically or microbiologically defined variant of periodontal
      disease. The frequency and consequences of adverse effects of antibiotics have
      always to be balanced against the potential consequences of not rapidly
      suppressing a periodontal infection. Proposed strategies to reduce the risk of
      bacterial antimicrobial resistance include: prescribing two drugs with a
      synergistic or complementary effect, the administration of antibiotics at a high
      dose for a short period, a combined approach with mechanical debridement to
      disrupt biofilms, and the focus on therapeutic rather than prophylactic use.
      Derivatives of existing antibiotic classes and new compounds that act on unique
      targets are the subject of preclinical investigations with a focus on action
      against antibiotic-resistant medical pathogens. In light of the excellent results
      of a combination therapy with well-established drugs that are cheap and
      efficient, clinical trials should compare newly proposed protocols for
      periodontal therapy to a positive control. Future studies should focus not only
      on the action against the microorganisms directly involved in periodontal
      diseases, but also on those relevant to other medical concerns.

PMID- 22142960
TI  - Animal models to study host-bacteria interactions involved in periodontitis.
AB  - Animal models have distinct advantages because they can mimic cellular
      complexities that occur in humans in vivo and are often more accurate than in
      vitro studies that take place on plastic surfaces with limited numbers of cell
      types present. Furthermore, cause and effect relationships can be established by
      applying inhibitors or activators or through the use of genetically modified
      animals. Such gain or loss of function studies are often difficult to achieve in
      human clinical studies, particularly in obtaining target tissue due to important
      ethical considerations. Animal models in periodontal disease are particularly
      important at this point in the development of the scientific basis for
      understanding the predominant pathological processes. Periodontal disease can be
      broken down into discrete steps, each of which may be studied separately
      depending upon the animal model. These steps involve the development of a
      pathogenic biofilm, invasion of connective tissue by bacteria or their products,
      induction of a destructive host response in connective tissue and limitation of
      are pair process that follows tissue breakdown. Animal studies can test
      hypotheses related to each of these steps, and should be evaluated by their
      capacity to test a specific hypothesis rather than recapitulating all aspects of
      periodontal disease. Thus, each of the models described below can be adapted to
      test discrete components of the pathological process of periodontal disease, but
      not necessarily all of them.

PMID- 22142962
TI  - Regenerative periodontal therapy.
AB  - Traditional treatment for loss of bone and attachment due to periodontal disease
      has focused around repairing the damage induced. However, over the past few
      decades, clinicians have begun to utilize regenerative techniques to rebuild
      bone, cementum and the periodontal ligament. Conventional procedures most often
      involve the use of barrier membranes with bone grafts that foster selective cell
      repopulation and regrowth of osseous structures. Since the predictability of
      these techniques may be limited to certain case types, pharmacologically based
      efforts are underway to investigate the possibility of harnessing osseous
      regrowth potential. Clinical research has found that proteins are potent
      biological mediators that promote many of the events in wound healing, and have
      been shown to promote bone formation in human clinical studies.

PMID- 22142963
TI  - Paradigm shift in the pharmacological management of periodontal diseases.
AB  - It is becoming clear that variations in inflammatory response are a major
      determinant in susceptibility to periodontitis. However, our understanding of the
      relationship of the causal agents in periodontitis to the pathogenesis is not as
      clear as we once thought, and thus therapies based on etiopathogenesis are
      similarly in question. We are entering a new era of therapeutic discovery that
      may have a major impact on our management of the periodontal diseases.
      Fundamentally, periodontitis is an irreversible condition and once both soft and
      hard tissues are lost, the healthy periodontal architecture cannot be completely
      or predictably rebuilt. The discovery of new families of lipid mediators of
      resolution of inflammation (the lipoxins) and eicosapentaenoic-acid- and
      docosahexaenoic-acid-derived chemical mediators (the resolvins and protectins)
      opens new avenues to designing resolution-targeted therapies to control the
      unwanted side effects of excessive inflammation. The novel protective and
      therapeutic actions of pro-resolution lipid mediators following microbial
      challenge are mediated by regulation of the local and systemic inflammatory
      response that has a direct impact on the organization of the biofilm (plaque) and
      suggests a new paradigm in clinical periodontal therapeutics.

PMID- 22142965
TI  - Effects of monounsaturated fatty acids on cardiovascular risk factors: a
      systematic review and meta-analysis.
AB  - The appropriate pattern of macronutrient distribution for dietary protocols aimed
      at treating or preventing obesity and its associated cardiovascular diseases is
      still a controversial topic of discussion. Recommendations considering a specific
      percentage or range for monounsaturated fatty acids (MUFA) are rare. It was the
      aim of this study to analyze long-term, randomized, controlled dietary
      intervention trials and to investigate the effects of MUFA on the biomarkers of
      obesity and cardiovascular risk factors. Dietary regimens with a high amount of
      MUFA (>12%) were compared to those with <=12%. The biomarkers taken into account
      were weight, waist circumference, fat mass, total cholesterol, LDL cholesterol,
      HDL cholesterol, triacylglycerols, systolic and diastolic blood pressure, as well
      as C-reactive protein. A total of 12 studies met the inclusion criteria. Data
      analysis was performed using the Review Manager 5.0.25 software. Significant
      differences between high- and low-MUFA protocols could be observed with respect
      to fat mass [-1.94 kg (confidence interval -3.72, -0.17), p = 0.03], systolic
      blood pressure [-2.26 mm Hg (confidence interval -4.28, -0.25), p = 0.03] and
      diastolic blood pressure [-1.15 mm Hg (confidence interval -1.96, -0.34), p =
      0.005] favoring the dietary protocols with >12% MUFA. Therefore, MUFA might
      represent a useful tool in the design of dietary regimens for obesity and
      cardiovascular disease.

PMID- 22142964
TI  - Differential regulation of epiboly initiation and progression by zebrafish
      Eomesodermin A.
AB  - The T-box transcription factor Eomesodermin (Eomes) has been implicated in
      patterning and morphogenesis in frog, fish and mouse. In zebrafish, one of the
      two Eomes homologs, Eomesa, has been implicated in dorsal-ventral patterning,
      epiboly and endoderm specification in experiments employing over-expression,
      dominant-negative constructs and antisense morpholino oligonucleotides. Here we
      report for the first time the identification and characterization of an Eomesa
      mutant generated by TILLING. We find that Eomesa has a strictly maternal role in
      the initiation of epiboly, which involves doming of the yolk cell up into the
      overlying blastoderm. By contrast, epiboly progression is normal, demonstrating
      for the first time that epiboly initiation is genetically separable from
      progression. The yolk cell microtubules, which are required for epiboly, are
      defective in maternal-zygotic eomesa mutant embryos. In addition, the deep cells
      of the blastoderm are more tightly packed and exhibit more bleb-like protrusions
      than cells in control embryos. We postulate that the doming delay may be the
      consequence both of overly stabilized yolk cell microtubules and defects in the
      adhesive properties or motility of deep cells. We also show that Eomesa is
      required for normal expression of the endoderm markers sox32, bon and og9x;
      however it is not essential for endoderm formation.

PMID- 22142966
TI  - Adverse birth outcomes and maternal exposure to trichloroethylene and
      tetrachloroethylene through soil vapor intrusion in New York State.
AB  - BACKGROUND: Industrial spills of volatile organic compounds (VOCs) in Endicott,
      New York (USA), have led to contamination of groundwater, soil, and soil gas.
      Previous studies have reported an increase in adverse birth outcomes among women
      exposed to VOCs in drinking water. OBJECTIVE: We investigated the prevalence of
      adverse birth outcomes among mothers exposed to trichloroethylene (TCE) and
      tetrachloroethylene [or perchloroethylene (PCE)] in indoor air contaminated
      through soil vapor intrusion. METHODS: We examined low birth weight (LBW),
      preterm birth, fetal growth restriction, and birth defects among births to women
      in Endicott who were exposed to VOCs, compared with births statewide. We used
      Poisson regression to analyze births and malformations to estimate the
      association between maternal exposure to VOCs adjusting for sex, mother's age,
      race, education, parity, and prenatal care. Two exposure areas were identified
      based on environmental sampling data: one area was primarily contaminated with
      TCE, and the other with PCE. RESULTS: In the TCE-contaminated area, adjusted rate
      ratios (RRs) were significantly elevated for LBW [RR = 1.36; 95% confidence
      interval (CI): 1.07, 1.73; n = 76], small for gestational age (RR = 1.23; 95% CI:
      1.03, 1.48; n = 117), term LBW (RR = 1.68; 95% CI: 1.20, 2.34; n = 37), cardiac
      defects (RR = 2.15; 95% CI: 1.27, 3.62; n = 15), and conotruncal defects (RR =
      4.91; 95% CI: 1.58, 15.24; n = 3). In the PCE-contaminated area, RRs for cardiac
      defects (five births) were elevated but not significantly. Residual socioeconomic
      confounding may have contributed to elevations of LBW outcomes. CONCLUSIONS:
      Maternal residence in both areas was associated with cardiac defects. Residence
      in the TCE area, but not the PCE area, was associated with LBW and fetal growth
      restriction.

PMID- 22142967
TI  - Neutrophil-mediated lung damage: a new COPD phenotype?

PMID- 22142968
TI  - Validation of the Malnutrition Universal Screening Tool (MUST) in cancer.
AB  - In the present study, we aimed to validate the Malnutrition Universal Screening
      Tool (MUST) for routine nutritional screening in the radiation oncology setting,
      thus enabling timely and adequate referrals of patients at risk for
      individualised or advanced intervention. Towards this objective, we conducted a
      prospective cross-sectional study in 450 non-selected cancer patients (18-95
      years) referred for radiotherapy. The following were the nutritional parameters:
      BMI (categorised by WHO's age/sex criteria), weight loss >5 % in the previous 3-6
      months, Patient-Generated Subjective Global Assessment (PG-SGA -
      validated/specific for oncology) and nutritional risk by MUST. Sensitivity,
      specificity, predictive values and concordance were calculated to validate MUST
      v. PG-SGA and compare single parameters v. PG-SGA/MUST. BMI v. PG-SGA showed a
      negligible capacity to detect undernutrition: 0.27 sensitivity, 0.23 specificity,
      0.35 positive predictive value and 0.31 negative predictive value. Conversely,
      percentage weight loss v. PG-SGA was highly effective: 0.76 sensitivity, 0.85
      specificity, 0.79 positive predictive value and 0.85 negative predictive value.
      MUST v. PG-SGA successfully detected patients at risk: 0.80 sensitivity, 0.89
      specificity, 0.87 positive predictive value and 1.0 negative predictive value;
      percentage weight loss v. MUST proved able to identify patients likely to be at
      risk: 0.85 sensitivity, 0.91 specificity, 0.90 positive predictive value and 1.0
      negative predictive value. This is the first study in the radiation oncology
      setting to validate MUST: a simple and quick method applicable by any health
      professional, with a high validity for early screening, ideally to antedate a
      comprehensive nutritional assessment and guide for intervention. In this study,
      percentage weight loss in the previous 3-6 months does seem valid to predict
      nutritional risk, and may be the minimum in a busy routine.

PMID- 22142969
TI  - Effect of varying flow regimes upon elution behaviour, apparent molecular
      characteristics and hydrodynamic properties of amylopectin isolated from normal
      corn starch using asymmetrical flow field-flow fractionation.
AB  - A detailed study of the elution behaviour, apparent molecular characteristics and
      hydrodynamic properties of amylopectin-type fraction (isolated from normal corn
      starch) in aqueous media employing asymmetrical flow field-flow fractionation
      (AF4) was undertaken by systematically varying the channel flow (F(ch)), cross
      flow (F(cr)) and F(cr)/F(ch) ratios. Distributions of apparent molar masses and
      radii of gyration, mass recoveries and hydrodynamic radii decreased as a function
      of increasing F(cr) at a fixed F(ch), due to the increase in the retention of
      amylopectin-type fraction in the AF4 channel. Increased retention of the
      amylopectin-type fraction in the AF4 channel was also observed at low F(ch) and
      high F(cr)/F(ch) ratios. Large amylopectin-type molecules/particles (possibly
      aggregates) eluted at high F(ch), low F(cr) and low F(cr)/F(ch) ratios.

PMID- 22142970
TI  - Simultaneous determination of thirty non-steroidal anti-inflammatory drug
      residues in swine muscle by ultra-high-performance liquid chromatography with
      tandem mass spectrometry.
AB  - An ultra-high-performance liquid chromatography with tandem mass spectrometric
      detection (UHPLC-MS/MS) method was established for the simultaneous determination
      of residues of thirty non-steroidal anti-inflammatory drugs (NSAIDs) in swine
      muscle. The samples were extracted with acetonitrile and phosphoric acid. The
      extracts were defatted with n-hexane, and then purified by HLB solid-phase
      extraction cartridge. Analysis was carried out on UHPLC-ESI-MS/MS working with
      multiple reaction monitoring mode with polarity switching. Limits of detection
      were between 0.4 MUg/kg and 2.0 MUg/kg, and limits of quantification were between
      1.0 MUg/kg and 5.0 MUg/kg. The recoveries of NSAIDs were between 61.7% and 125.7%
      at spiked levels of 1.0-500 MUg/kg. The repeatability was less than 8% and the
      within-laboratory reproducibility was not more than 12.3%. The method was
      reliable, convenient and sensitive.

PMID- 22142971
TI  - Combined use of isopropylamine and trifluoroacetic acid in methanol-containing
      mobile phases for chiral supercritical fluid chromatography.
AB  - In chiral supercritical fluid chromatography (SFC), mobile-phase additives are
      often used to improve enantioseparations and peak shapes. An acidic or basic
      additive is chosen, depending on the nature of the compound. This work highlights
      the simultaneous use of the acidic additive trifluoroacetic acid (TFA) and the
      basic additive isopropylamine (IPA) in supercritical fluid chromatography for
      enantioseparations. To evaluate the combination of TFA and IPA, 59 chiral
      pharmaceutical compounds were analyzed on four polysaccharide-based chiral
      stationary phases (CSPs): Lux(r) Cellulose-1, Lux(r) Cellulose-2, Lux(r)
      Cellulose-4 and Lux(r) Amylose-2. The results show that an important increase in
      enantioselectivity of the chromatographic system can occur when combining
      trifluoroacetic acid and isopropylamine in the mobile phase (MP), compared to the
      individual use of these additives. However, the combination of isopropylamine and
      trifluoroacetic acid in a supercritical methanol-containing mobile phase can also
      lead to problems as a result of the formation of salt complexes between the two
      additives. Combining the additives trifluoroacetic acid and isopropylamine and
      taking the appropriate measures to avoid salt formation, i.e. reducing the
      additives' concentrations, can lead to simpler chiral SFC screening conditions
      that display even broader enantioselectivity.

PMID- 22142972
TI  - The age of the "ome": genome, transcriptome and proteome data set collection and
      analysis.
AB  - The current state of human genetic studies is both a marvel and a morass. A
      marvel in that with the completion of the human genome sequence, projects that
      used to take years now take months or weeks; however, this creates a wealth of
      data concomitant to a black hole of meaning. In terms of the well used analogy:
      the human genome sequence is a library in an ancient language with no Rosetta
      stone. Researchers have readily exploited the human genome map and thousands of
      candidate gene studies for a multitude of diseases have been performed. However,
      many of those studies have found that the variants associated with disease risk
      are not obvious coding changes. The question now becomes: what do these
      associations mean? One approach to the downstream mapping of associations is to
      use additional information to map which variant might truly be causative of risk
      and what that risk variant is doing. This review will summarize the current state
      of both data set collection and analysis for the understanding of DNA variants
      and their downstream effects on transcripts and proteins. This article is part of
      a Special Issue entitled 'Transcriptome'.

PMID- 22142975
TI  - Physical health problems after single trauma exposure: when stress takes root in
      the body.
AB  - Research has established that chronic stress, including traumatic events, leads
      to adverse health outcomes. The literature has primarily used two approaches:
      examining the effect of acute stress in a laboratory setting and examining the
      link between chronic stress and negative health outcomes. However, the potential
      health impact of a single or acute traumatic event is less clear. The goal of
      this literature review is to extend the literature linking both chronic trauma
      exposure and posttraumatic stress disorder to adverse health outcomes by
      examining current literature suggesting that a single trauma may also have
      negative consequences for physical health. The authors review studies on health,
      including cardiovascular, immune, gastrointestinal, neurohormonal, and
      musculoskeletal outcomes; describe potential pathways through which single, acute
      trauma exposure could adversely affect health; and consider research and clinical
      implications.

PMID- 22142974
TI  - Loop nucleotides control primary and mature miRNA function in target recognition
      and repression.
AB  - MicroRNA (miRNA) genes produce three major RNA products; primary (pri-),
      precursor (pre-), and mature miRNAs. Each product includes sequences
      complementary to cognate targets, thus they all can in principle interact with
      the targets. In a recent study we showed that pri-miRNAs play a direct role in
      target recognition and repression in the absence of functional mature miRNAs.
      Here we examined the functional contribution of pri-miRNAs in target regulation
      when full-length functional miRNAs are present. We found that pri-let-7 loop
      nucleotides control the production of the 5' end of mature miRNAs and modulate
      the activity of the miRNA gene. This insight enabled us to modulate biogenesis of
      functional mature miRNAs and dissect the causal relationships between mature
      miRNA biogenesis and target repression. We demonstrate that both pri- and mature
      miRNAs can contribute to target repression and that their contributions can be
      distinguished by the differences between the pri- and mature miRNAs' sensitivity
      to bind to the first seed nucleotide. Our results demonstrate that the regulatory
      information encoded in the pri-/pre-miRNA loop nucleotides controls the
      activities of pri-miRNAs and mature let-7 by influencing pri-miRNA and target
      complex formation and the fidelity of mature miRNA seed generation.

PMID- 22142977
TI  - Inflammation and traumatic stress: the society to cells resiliency model to
      support integrative interventions.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent psychiatric
      disorder that develops following a traumatic event and has substantial health
      implications, including high rates of health morbidity and mortality, as well as
      significant health-related costs. Medical risks that are associated with PTSD
      often have an underlying inflammatory pathology, suggesting that inflammation
      contributes to these health declines. OBJECTIVES AND DESIGN: In this critical
      literature review, the authors examine the medical risks associated with PTSD and
      the inflammatory mechanisms that likely underlie these risks. RESULTS AND
      CONCLUSIONS: The authors offer a review of their "Cells to Society Resiliency
      Model" to motivate the development of integrative interventions that include
      factors of society, community, family, individual, physiological, and cellular
      factors to thereby reduce the health risks associated with PTSD.

PMID- 22142973
TI  - Mouse models of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia, affecting 35
      million people today. The search for new treatments is made ever more urgent by
      prospects for increasing prevalence due to population aging. Mouse models are one
      of the most important research tools for finding new treatments for AD. Here, we
      review those models. We begin by briefly reviewing the AD genetics on which mouse
      models are based and then consider the most common mouse models of AD, including
      mice transgenic for human amyloid precursor protein (hAPP) and beta-amyloid
      (Abeta), mice expressing mutant presenilin genes, mice modeling tau's role in AD,
      and apolipoprotein E models. The discussion highlights key features and important
      differences between these mouse models. We conclude with a discussion about the
      role of AD mouse models in the translational pipeline.

PMID- 22142976
TI  - Implications of hypothalamic-pituitary-adrenal axis functioning in posttraumatic
      stress disorder.
AB  - BACKGROUND: Cortisol secretions serve as the barometer of the hypothalamic
      pituitary-adrenal (HPA) axis, which regulates and controls responses to stress.
      Studies of cortisol secretions in patients with posttraumatic stress disorder
      (PTSD) reveal inconsistent results. PURPOSE: Current research on HPA axis
      functioning in PTSD is examined to elucidate the neuroendocrine contributions in
      the disorder, identify current treatment's impact on the HPA axis, and consider
      implications for nursing care and areas for future research. FINDINGS: There is
      evidence for HPA dysregulation in PTSD, which contributes to widespread
      impairment in functions such as memory and stress reactivity and to physical
      morbidity via processes such as allostatic load. There is limited, but building,
      evidence that dehydroepiandrosterone (DHEA), which is released simultaneously
      with cortisol, may provide anti-glucocorticoid and neuroprotective effects.
      CONCLUSION: Current treatments such as selective serotonin reuptake inhibitors
      and psychotherapy may have a beneficial impact on the HPA axis in PTSD
      populations. Somatic approaches to treating PTSD have not yet been studied in
      relation to their impact on HPA axis parameters in PTSD patients. Treatment
      studies of DHEA or glucocorticoids have not yet used HPA axis endpoints. PTSD
      treatment studies that include measures of HPA axis target mechanisms and
      consider HPA axis regulation as an additional treatment outcome are warranted.

PMID- 22142978
TI  - Antenatal psychobiological predictors of psychological response to childbirth.
AB  - BACKGROUND: Several psychological and obstetric predictors of a negative
      childbirth experience and traumatic response to delivery have been identified.
      However, the influence of antepartum physiological stress parameters has not been
      elucidated. OBJECTIVE: The study includes an exploratory analysis of the
      associations of fear of delivery, antenatal basal and reactive activity of the
      hypothalamic-pituitary-adrenal axis, and obstetric outcomes, with childbirth
      experience and posttraumatic avoidance in the postpartum period. DESIGN: This was
      a prospective study with two antenatal measurements and a final assessment during
      the first week postpartum. An experimental condition with a standardized stressor
      (Trier Social Stress Test) was included in the design to study psychobiological
      stress response as a predictor of traumatic birth and posttraumatic avoidance.
      RESULTS: Linear regression analyses show independent associations of fear of
      delivery and more pronounced antenatal cortisol awakening response with a more
      negative childbirth experience. Fear of delivery was mediated by state anxiety
      after stress exposure, which, together with cortisol awakening response,
      explained 16% of the variance in the outcome of a more negative childbirth
      experience. Finally, antenatal fear of delivery and a negative childbirth
      experience both predicted higher avoidance scores during the first week
      postpartum. CONCLUSIONS: The associations found in this study can improve
      identification during pregnancy of women at risk for negative psychological
      response to childbirth. For these women, the provision of supportive care during
      pregnancy should be evaluated.

PMID- 22142979
TI  - A clinical translation of the research article titled "antenatal psychobiological
      predictors of psychological response to childbirth".

PMID- 22142980
TI  - Evidence-based practice principles: using the highest level when evidence is
      limited.
AB  - Clinicians providing psychiatric care are often faced with selecting
      interventions in areas of care for which there is limited scientific support,
      such as the information on traumatic stress responses and integrated care
      interventions. If they adhere to the principles of evidence-based practice (EBP),
      the lack of scientific support should not hamper clinicians from implementing the
      best EBP intervention. EBP interventions can be drawn from the literature
      provided clinicians accurately appraise the level of existing scientific
      knowledge. Regardless of the level of evidence, clinicians must discuss the
      recommended intervention, risks, benefits, and alternatives to achieve the best
      EBP outcome.

PMID- 22142982
TI  - The global challenges in work for Oral Health of All. Foreword.

PMID- 22142983
TI  - 30 years of burn disasters within the UK: guidance for UK emergency preparedness.
AB  - AIM: To review casualty profiles of major UK burn disasters over the last 30
      years in order to provide guidance to aid burn and emergency service planning and
      provision so as to improve emergency preparedness for future national disasters.
      METHODS: A review of published literature was undertaken for disasters within the
      UK that had occurred between 1980 and 2009. Those producing 10 or more casualties
      with at least one sustaining cutaneous burns injuries were included. Frequency
      and extent of burns were recorded and analysed. RESULTS: In total 37 disasters
      were included in this study, their frequency of occurrence falling over the 30
      years reviewed. Burns tended to make up a small proportion of all casualties and
      were often relatively small in size with only 3 disasters having more than 5
      patients with >10% burns. DISCUSSION: This paper can help guide appropriate
      staffing and bed capacity planning for regional burns units and provide realistic
      figures to guide scenarios for national emergency training exercises. Due to the
      infrequent nature of major disasters, Critical Care, Trauma Care and Burn Care
      Networks will all need to be closely integrated and their implementation
      rehearsed so as to ensure optimal response to a major national disaster.

PMID- 22142985
TI  - Weaning from mechanical ventilation.
AB  - PURPOSE OF REVIEW: Liberation from mechanical ventilation is a defining moment
      for intubated patients, and thus a critical clinical decision. Extubating the
      patient too early exposes the patient to extubation failure and reintubation.
      Waiting too long increases the complications of prolonged intubation. Tools to
      help the physician with this critical decision and to test readiness have been
      available for decades, and are continuously being improved. New methods to
      improve extubation outcomes are also being developed. This review covers the
      latest studies in order to help physicians take advantage of the latest
      developments in a rapidly evolving field. RECENT FINDINGS: This review highlights
      the recent advances in assessing and testing for readiness of weaning and
      liberation from mechanical ventilation, the cause of weaning failure, the value
      of weaning protocols, and the role of noninvasive positive pressure ventilation
      in liberating patients from invasive mechanical ventilation. SUMMARY: Recent
      findings are shedding more light on this topic, and transforming 'the artistic'
      aspect of weaning and liberation from mechanical ventilation into a more
      'scientific' approach that will expedite liberation from mechanical ventilation
      yet without encountering high failure rates, and without exposing patients to
      unnecessary risks.

PMID- 22142984
TI  - Modulation of innate immunity in chickens induced by in vivo administration of
      baculovirus.
AB  - Baculoviruses stimulate cytokine production in mammalian cells. They induce a
      strong innate immune response in animals and have adjuvant properties. The
      purpose of this work was to study the in vivo effect of baculovirus on chicken
      innate immune response. SPF chickens were inoculated intravenously with
      Autographa californica nuclear polyhedrosis virus (BV). Three hours later,
      chickens were bled, euthanized and their spleen, duodenum and cecal tonsils were
      excised in order to take samples for RNA extraction and real time PCR, and to
      isolate lymphocytes, which were stained and analyzed by flow cytometry. The
      results obtained showed that baculovirus inoculation up-regulates the expression
      of IFN-gamma, IL-6 and LITAF in spleen cells. This result (IFN-gamma) correlated
      with that obtained by ELISA which showed a very strong increase of IFN-gamma in
      chicken plasma. Flow cytometry analysis revealed that BV inoculation induced in
      spleen an increase in the percentage of monocyte/macrophage population together
      with an increase in CD3(+)CD4(+) T lymphocytes. On the other hand, BV inoculation
      decreased the percentage of CD3(+)CD4(+) T lymphocytes and increased the
      percentage of NK cells in cecal tonsils. However, intraepithelial lymphocytes of
      the gut did not show differences between BV and control treated animals. Even
      though further studies in order to understand the mechanisms by which BVs affect
      the avian immune response are needed, results obtained in the present work
      demonstrate the ability of BVs to stimulate the innate immunity in chickens,
      modifying the expression pattern of related genes and the profile of the immune
      cells involved.

PMID- 22142986
TI  - Celiac crisis/refeeding syndrome combination:  new mechanism for an old
      complication.

PMID- 22142987
TI  - Retraction. Protein kinase Cdelta regulates endothelial nitric oxide synthase
      expression via Akt activation and nitric oxide generation.

PMID- 22142988
TI  - The changing profile of autopsied deaths in the United States, 1972-2007.
AB  - An autopsy, the medical examination of a deceased person, may confirm clinical
      findings, provide more complete information to describe cause of death, or
      uncover conditions not recognized clinically prior to death. Two types are
      performed in the United States: a) hospital or clinical autopsies, which family
      or physicians request to clarify cause of death or assess care, and b)
      medicolegal autopsies, which legal officials order to further investigate the
      circumstances surrounding a death. The autopsy rate, or percentage of deaths that
      received this final assessment, was stable from the 1950s until the beginning of
      the 1970s, when the autopsy rate began to decrease. This report uses mortality
      data from the National Vital Statistics System (NVSS) over a 35-year period to
      examine changes in the autopsy rate and in the distribution of those autopsied by
      age and cause. Variation in autopsy patterns has implications for which deaths
      may have a more complete and conclusive cause-of-death determination.

PMID- 22142989
TI  - Ergonomics in developing hand operated maize dehusker-sheller for farm women.
AB  - A hand operated maize dehusker-sheller to be operated by farm women was designed
      and developed to dehusk and shell the maize cobs using ergonomics
      (anthropometric, strength and physiological workload). Axial-flow maize dehusker
      sheller with 540 mm cylinder length and 380 mm diameter required 3.03 N-m torque
      on cylinder shaft while operating at 5.6 m s(-1) peripheral speed and 100 kg h(
      1) feed rate by feeding cob one by one. This torque was 30% of isometric torque
      obtained at front position of handle (greatest distance) with lowest crank
      length. The heart rate of subject while operating the maize dehusker-sheller at
      54 rpm (5.6 m s(-1)) was 142 beats min(-1). The output of 60 kg h(-1) was
      obtained at the feed rate of 80 kg h(-1). Two subjects can operate the machine
      for an hour with a rest pause of 15 min by swapping the operation.

PMID- 22142991
TI  - Effects of an intervention and maintenance weight loss diet with and without
      exercise on anthropometric indices in overweight and obese healthy women.
AB  - BACKGROUND AND AIMS: There is growing evidence that excess body weight and body
      fat levels may lead to various diseases. A low-calorie diet has been found to
      reduce body weight and fat; however, 95% of patients regain the weight within a
      short period of time. The aim of this study was to investigate the effects of a
      reduced-calorie diet with and without exercise on body composition profile as
      well as to evaluate maintenance of weight loss 18 weeks after the intervention
      had concluded. METHODS: Two hundred and six overweight and/or obese women were
      randomized by a computer to either diet only (DO) or diet and exercise (DE) for
      an 18-week intervention period and 18 weeks of maintenance. Statistical
      significance was set at p < 0.05. RESULTS: Body mass index (BMI) was reduced by
      5.1 in the DE group compared to 3.2 in the DO group 18 weeks after the
      intervention period had ended; waist circumference (WC) was 14.2 cm lower in the
      exercise group and 8 cm lower in the diet alone group, and body fat was reduced
      by 15.5% in the DE group, while no changes were observed in the DO group.
      CONCLUSION: A combination of a reduced-calorie diet with exercise may
      successfully reduce weight, BMI, WC and body fat levels.

PMID- 22142990
TI  - Estradiol increases cell growth in human astrocytoma cell lines through ERalpha
      activation and its interaction with SRC-1 and SRC-3 coactivators.
AB  - Estradiol (E2) regulates several cellular functions through the interaction with
      estrogen receptor subtypes, ERalpha and ERbeta, which present different
      functional and regulation properties. ER subtypes have been identified in human
      astrocytomas, the most common and aggressive primary brain tumors. We studied the
      role of ER subtypes in cell growth of two human astrocytoma cell lines derived
      from tumors of different evolution grades: U373 and D54 (grades III and IV,
      respectively). E2 significantly increased the number of cells in both lines and
      the co-administration with an ER antagonist (ICI 182, 780) significantly blocked
      E2 effects. ERalpha was the predominant subtype in both cell lines. E2 and ICI
      182, 780 down-regulated ERalpha expression. The number of U373 and D54 cells
      significantly increased after PPT (ERalpha agonist) treatment but not after DPN
      (ERbeta agonist) one. To determine the role of SRC-1 and SRC-3 coactivators in
      ERalpha induced cell growth, we silenced them with RNA interference. Coactivator
      silencing blocked the increase in cell number induced by PPT. The content of
      proteins involved in proliferation and metastasis was also determined after PPT
      treatment. Western blot analysis showed that in U373 cells the content of PR
      isoforms (PR-A and PR-B), EGFR, VEGF and cyclin D1 increased after PPT treatment
      while in D54 cells only the content of EGFR was increased. Our results
      demonstrate that E2 induces cell growth of human astrocytoma cell lines through
      ERalpha and its interaction with SRC-1 and SRC-3 and also suggest differential
      roles of ERalpha on cell growth depending on astrocytoma grade.

PMID- 22142992
TI  - Pharmacological evidence for the role of nitric oxide in the modulation of stress
      induced anxiety by morphine in rats.
AB  - The present study evaluated the effects of the opioid agonist, morphine on stress
      induced anxiogenesis and the possible involvement of nitric oxide (NO) in such
      effects in rats. Acute restraint stress consistently induced an anxiety-like
      response in the elevated plus maze test, i.e. reduced number of open arm entries
      and time spent in the open arms as compared to controls. Pretreatment with
      morphine (1 and 5mg/kg), attenuated the restraint stress induced anxiogenic
      response in a dose related manner. Restraint stress induced neurobehavioral
      suppression was associated with reductions in brain NO oxidation products (NOx)
      levels, which were also reversed with morphine. Interaction studies showed that
      sub-effective doses of morphine and l-arginine (a NO precursor) had synergistic
      effects on stress induced elevated plus maze activity and brain NOx, whereas, l
      NAME (a NO synthase inhibitor) neutralized these effects of morphine. Repeated
      restraint stress (*5) induced adaptative changes as evidenced by normalization of
      behavioral suppression and elevations in brain NOx, as compared to acute stress.
      Pretreatment with morphine in combination with repeated stress (*5) showed
      potentiating effects in the induction of behavioral adaptation in the elevated
      plus maze and elevations in brain NOx, as compared to repeated stress alone.
      Further, l-NAME, when administered prior to morphine, blocked this effect of
      morphine on stress adaptation. These results suggest differential morphine-NO
      interactions during acute and repeated restraint stress.

PMID- 22142993
TI  - Effects of the GABAB receptor agonist baclofen on primary drinking in rats.
AB  - The effects of subcutaneous (s.c.) administration of the GABA(B) receptor agonist
      baclofen were investigated on primary drinking in rats. Baclofen (1-4 mg/kg)
      produced a dose-related reduction in cumulative water intake in 16 h water
      deprived rats during the 120 min measurement period (Experiment 1). The
      suppressant effect of baclofen (2mg/kg) on water intake 16 h water-deprived rats
      was significantly attenuated by pretreatment with the GABA(B) receptor antagonist
      CGP 35348 (3-aminopropyl (diethoxymethyl)-phosphinic acid; 50mg/kg; s.c.,
      Experiment 2.), indicating that the hypodipsic effects of the drug in thirsty
      rats are mediated by an action at GABA(B) receptors. Experiment 3 was undertaken
      to investigate the effects of baclofen on volemic drinking induced in rats
      pretreated with propylene glycol. S.C. administration of polyethylene glycol
      induces volemic drinking in rats by reducing extracellular fluid. Baclofen
      (2mg/kg, s.c.) significantly reduced the volemic drinking in rats pretreated with
      polyethylene glycol (30% w/v solution). Experiment 4 was conducted to investigate
      the effects of baclofen on osmotic drinking in non-deprived rats pretreated with
      hypertonic sodium chloride (NaCl) solution. Hypertonic NaCl will draw out
      intracellular fluid to stimulate osmotic drinking. Baclofen (2mg/kg; s.c.)
      significantly reduced osmotic drinking in rats pretreated with 1 ml hypertonic
      NaCl (16% w/v). The results of this study indicate that (i) the hypodipsic effect
      of baclofen in water-deprived rats is mediated by an action at GABA(B) receptors
      and (ii) baclofen suppresses both volemic and osmotic drinking.

PMID- 22142994
TI  - Positive family history of thyroid disease as a risk factor for differentiated
      thyroid carcinoma.
AB  - INTRODUCTION: Apart from the environmental risk factors for differentiated
      thyroid carcinoma (DTC), such as iodine deficiency and ionising radiation, it
      seems that there are also other, biological risk factors, for example, familial
      predisposition to thyroid disease. OBJECTIVES: The aim of the study was to assess
      the occurrence of thyroid disease in the families of patients with DTC. PATIENTS
      AND METHODS: A case-control study was conducted in a group of 232 patients with
      DTC and in 342 age- and sex-matched healthy subjects. Eighty patients were
      diagnosed with follicular thyroid carcinoma, 127 with papillary thyroid
      carcinoma, and 25 with oxyphilic thyroid carcinoma. The questionnaire included
      questions on the presence of thyroid diseases in first-degree relatives. The
      relative risk of DTC and the effect of factors associated with thyroid diseases
      in the family were assessed by the logistic regression model. RESULTS: Thyroid
      disease was more common in the families of DTC patients than in the control
      group: 18.5% of the patients and 9.6% of the control group had a parent with
      thyroid disease (OR = 2.12, 95% CI: 1.26-3.55); 16.8% of the patients and 7.7% of
      the control group had a sibling with thyroid disease (OR = 2.27, 95% CI: 1.31
      3.95). CONCLUSIONS: Familial thyroid disease may be a risk factor for DTC. A
      positive family history of thyroid disease is associated to a larger extent with
      the development of papillary thyroid carcinoma than with that of follicular
      thyroid carcinoma.

PMID- 22142995
TI  - 'Evorego': studying regeneration to understand evolution, the case of the
      serotonergic system.

PMID- 22142996
TI  - Spontaneous tool-use: an observation of a dingo (Canis dingo) using a table to
      access an out-of-reach food reward.
AB  - Opportunities to observe non-human animals exhibiting naturalistic 'high-order'
      behaviour are rare. Examples featuring canids, although often anecdotal and
      involving captive animals are potentially valuable, as they may provide an
      opportunity to examine complex problem-solving behaviour not easily observed in
      free-ranging settings. This paper describes observations of two captive male
      dingoes (Canis dingo), representing possible examples of high-order behaviour.
      The first set of observations involved a sub-adult male that spontaneously (i.e.,
      without training) learned to move objects around his enclosure, apparently to
      multiple ends, such as in an effort to gain the additional height required to
      attain objects otherwise out of reach, or to attain a better view of his
      surroundings. The second set of observations involved an adult male that learned
      to open a gate, possibly in an effort to gain access to a female. These
      observations add to the small number of anecdotal accounts offering a window into
      the cognitive abilities of canids, and the observations involving the sub-adult
      male appear to be the first documented cases of tool-use in a canid.

PMID- 22142997
TI  - Sorption of metal cations by alginate-based biosorbents. On the correct
      determination of the thermodynamic parameters.
AB  - The paper is focused on the problem of interpretation of the experimental data
      related to the thermodynamics of metal ions binding by alginate-based
      biosorbents. When considering the thermodynamic parameters (i.e., changes in the
      enthalpy and entropy values; DeltaH and DeltaS, respectively), one can observe
      large discrepancies between their values even if the considered systems have very
      similar features. For instance, the binding of copper, cadmium, and lead can be
      entropy-driven, enthalpy-driven or both entropy- and enthalpy-driven, depending
      on the considered report. The aim of this paper is to find the reason for this
      paradox and to discuss the problem of interpretation of the data being usually
      the base for estimating DeltaH and DeltaS values. It appears that both numerous
      "technical" (e.g., pH, ionic strength) and model-related (e.g., monodentate vs.
      bidentate binding models) parameters can seriously influence the obtained values
      of thermodynamic parameters. The significance of these two types of factors is
      discussed in qualitative and quantitative manners. The proposed methods of
      distinguishing between the "apparent" and the "real" DeltaH and DeltaS values can
      be also related to other types of sorption/adsorption systems.

PMID- 22142998
TI  - Surface glycosylation of polysulfone membrane towards a novel complexing membrane
      for boron removal.
AB  - In this study, a novel complexing membrane was synthesized for boron removal from
      aqueous solution. A glycopolymer, poly(2-gluconamidoethyl methacrylate) (PGAMA),
      was grafted onto the chloromethylated polysulfone (CMPSF) microporous membrane
      via surface-initiated ATRP (SIATRP). The glycosylated PSF (GlyPSF) membrane was
      characterized by attenuated total refection-Flourier transform infrared
      spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and field
      emission scanning electron microscopy (FESEM). It was demonstrated that PGAMA was
      successfully anchored onto the membrane surface and the grafting yield can be
      tuned in a wide range up to 5.9 mg/cm(2) by varying the polymerization time. The
      complexing membrane can adsorb boron rapidly with the equilibrium reached within
      2h and has a remarkable high boron adsorption capacity higher than 2.0 mmol/g at
      optimized conditions. Freundlich, Langmuir, and Dubinin-Radushkevich adsorption
      isotherms were applied, and the data were best described by Langmuir model.
      Kinetic data were analyzed, and the data fitted very well to the pseudo-second
      order rate expression. The optimal pH for boron uptake is in a wide range of 6-9,
      and the optimal initial boron concentration is over 300 mg/L. Studies of ionic
      strength effects indicated the formation of inner-sphere surface complexes. The
      complexed boron can be leached quantitatively under acid condition.

PMID- 22142999
TI  - Antisolvent precipitation of hydrophobic functionalized multiwall carbon
      nanotubes in an aqueous environment.
AB  - The possibility of antisolvent precipitation of hydrophobic, organic soluble
      functionalized carbon nanotubes (f-CNTs), where water acts as an antisolvent is
      presented. Octadecylamine functionalized multiwall carbon nanotubes (MWCNT-ODA)
      was used as the model compound and was found to form highly stable dispersions in
      different water/solvent systems, and the particle sizes ranged from 170 to 400
      nm. Colloidal behavior was studied using dynamic light scattering and particle
      aggregation was found to increase with the addition of electrolytes, with
      tetrahydrofuran (THF) and ethanol showing the maximum effect. The aggregation
      behavior of the antisolvent precipitated system did not follow the conventional
      Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, which was different from what has
      been reported previously for hydrophilic, water soluble f-CNTs. Based on this
      study, it is evident that hydrophobic f-CNTs are potential water pollutants.

PMID- 22143000
TI  - Structural study on gold nanoparticle functionalized with DNA and its non-cross
      linking aggregation.
AB  - Hybridization of DNA tethered on colloidal nanoparticles with fully matched
      complementary one induces the aggregation of the particles in a non-cross-linking
      configuration. Here, we performed a structural study on DNA-functionalized gold
      nanoparticle and its non-cross-linking aggregation mainly using synchrotron
      radiation small-angle X-ray scattering. To understand the non-cross-linking
      aggregation, the nanoparticles with various DNA lengths and core sizes were used.
      In the aggregation, the surface distance between the gold nanoparticles increased
      with the length of DNA duplex, although the increment of the distance per base
      pair was not constant and showed the tendency to become small with increasing DNA
      length, meaning the interdigitation of DNA layers. The aggregation was also found
      to occur between the identical cores, without being affected by tethered DNA.
      Furthermore, it was proved that the relative increase in DNA length to core size
      leads to the increase in colloidal stability. Even the nanoparticles with full
      matched DNA duplex were dispersed stably. These facts suggested that van der
      Waals interaction between core particles rather than end-to-end stacking between
      DNA duplexes is a dominant attractive interaction. The steric repulsion force
      arising from entropic loss of thermal fluctuation of DNA molecules might be a key
      factor to characterize the non-cross-linking aggregation.

PMID- 22143001
TI  - Authoritative parenting style and adolescent smoking and drinking.
AB  - While peer influences have often found to be a risk factor in terms of adolescent
      substance use, parental variables may continue to serve as an adaptive and
      protective function, although the role of parents is more latent and
      controversial. Therefore, the main goal of this paper was to investigate the role
      of authoritative parenting style and other family variables in adolescents'
      smoking and drinking. Using a sample of Hungarian youth (N=2072; age range
      between 12 and 22; Mean=15.4 years, S.D.=1.8 years; 49,2% males) logistic
      regression analyses confirmed that authoritative parenting style (particularly
      responsiveness) and positive identification with parents may serve as a
      protection, whereas negative family interactions may act as a risk factor. These
      relationships are particularly decisive in case of monthly prevalence of drinking
      and both lifetime and current prevalence of smoking. Gender differences are
      slight (namely, parental control for boys, whereas responsiveness for girls seem
      to be more relevant), however, the role of certain parental variables may change
      with age. Although parental control tends to decrease among high school students,
      it even serves as a greater protection for those whose parents continue providing
      parental monitoring.

PMID- 22143002
TI  - Validity of Timeline Follow-Back for self-reported use of cannabis and other
      illicit substances--systematic review and meta-analysis.
AB  - BACKGROUND: Timeline Follow-Back (TLFB) is a widely used, calendar-based measure
      of self-reported use of (among other things) illicit substances. We examined
      agreement between TLFB and biological measures for illicit substances. METHODS:
      PubMed, PsycINFO, Cochrane CENTRAL, and EMBASE were searched in December 2010.
      16,633 papers screened to identify those that measured illicit substance use by
      both TLFB and biological measures. We extracted data on agreement between TLFB
      and biological measures, sample size, study type, inclusion criteria of
      participants, and length of recall of TLFB. RESULTS: Twenty-nine papers were
      included, almost exclusively in substance-use-disorder populations. Some studies
      reported several overall agreement rates, e.g. over time. Lowest and highest
      weighted average agreement rates were: for cannabis, 87.3% (95% confidence
      interval 86.9% to 87.7%) and 90.9% (90.5% to 91.4%); for cocaine, 79.3% (79.1% to
      79.6%) and 84.1% (83.9% to 84.2%); for opiates 94.0% (93.5% to 94.5%) for both
      weighted averages; and for studies not distinguishing between substances, 88.5%
      (88.4 to 88.7%) and 91.0% (90.7% to 91.2%). Higher agreement was found in
      populations without psychiatric comorbidity, and lower agreement in randomized
      controlled trials. Publication bias or selective outcome reporting bias was not
      detected. CONCLUSIONS: TLFB validly detects use of illicit substances in
      populations with substance use disorders. Using TLFB may limit the need for
      biological samples, making information on illicit substance use easier and less
      costly to obtain and analyze.

PMID- 22143003
TI  - The acquired preparedness risk model applied to smoking in 5th grade children.
AB  - The very early onset of smoking predicts numerous health problems. The authors
      conducted the first test of one risk model for elementary school age smoking,
      known as the acquired preparedness (AP) model of risk, in a cross-sectional
      sample of 309 5th grade children. The model posits that (a) impulsivity-related
      personality traits contribute to risk for a variety of risky, maladaptive
      behaviors; (b) smoking expectancies confer risk only for smoking; and (c) the
      personality traits contribute to the formation of high risk expectancies for
      reinforcement from smoking, which in turn increases the likelihood of early onset
      smoking. The model was supported: the high-risk personality traits distinguished
      children engaging in any risky, maladaptive behavior from other children, and the
      smoking expectancies differentiated smokers from all other children. The
      relationship between personality tendencies to act rashly when experiencing
      intense positive or negative emotions and smoker status was partially mediated by
      expectancies for reinforcement from smoking. This model should be investigated
      longitudinally.

PMID- 22143004
TI  - The neuropathological profile of mild cognitive impairment (MCI): a systematic
      review.
AB  - Whether mild cognitive impairment (MCI) has a distinct neuropathological profile
      that reflects an intermediate state between no cognitive impairment and dementia
      is not clear. Identifying which biological events occur at the earliest stage of
      progressive disease and which are secondary to the neuropathological process is
      important for understating pathological pathways and for targeted disease
      prevention. Many studies have now reported on the neurobiology of this
      intermediate stage. In this systematic review, we synthesize current evidence on
      the neuropathological profile of MCI. A total of 162 studies were identified with
      varied definition of MCI, settings ranging from population to specialist clinics
      and a wide range of objectives. From these studies, it is clear that MCI is
      neuropathologically complex and cannot be understood within a single framework.
      Pathological changes identified include plaque and tangle formation, vascular
      pathologies, neurochemical deficits, cellular injury, inflammation, oxidative
      stress, mitochondrial changes, changes in genomic activity, synaptic dysfunction,
      disturbed protein metabolism and disrupted metabolic homeostasis. Determining
      which factors primarily drive neurodegeneration and dementia and which are
      secondary features of disease progression still requires further research.
      Standardization of the definition of MCI and reporting of pathology would greatly
      assist in building an integrated picture of the clinical and neuropathological
      profile of MCI.

PMID- 22143006
TI  - Enforced expression of nuclear factor kappa B in p53 deficient keratinocytes
      induces cell cycle, angiogenic potential and tumorigenesis.
AB  - Multiple genetic mutations with subsequent molecular events are required for
      progression of normal epithelial cells to cancer, with p53 mutations being a very
      common event in squamous carcinogenesis. Upregulation of nuclear factor kappa B
      (NF-kappaB) is an associated feature of malignancy, however studies have not
      examined purposeful overexpression of the NF-kappaB p65 subunit in in vitro
      models of oral carcinogenesis. Our objective is to demonstrate that NF-kappaB p65
      transfection into p53 deficient Rhek keratinocytes produces carcinogenic
      progression. We constitutively over-expressed NF-kappaB p65 in Rhek
      keratinocytes, previously immortalized by SV 40 thus inactivating p53, and
      studied NF-kappaB dependent events. NF-kappaB p65 overexpression provided
      functional upregulation of NF-kappaB and produced cyclin D1-mediated
      proliferation and interleukin 8 transcription and secretion. Consequently, we
      demonstrated tumorigenesis in athymic mice with NF-kappaB p65 overexpressing
      cells. We conclude NF-kappaB p65 overexpression in p53 inactivated immortalized
      keratinocytes produces tumorigenesis, and that this single alteration in NF
      kappaB expression on a p53 inactivated background is sufficient for squamous
      carcinogenesis features, thus providing evidence that p65 may act as a gain of
      function oncogene in this setting.

PMID- 22143005
TI  - A review of research trends in physiological abnormalities in autism spectrum
      disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial
      dysfunction and environmental toxicant exposures.
AB  - Recent studies have implicated physiological and metabolic abnormalities in
      autism spectrum disorders (ASD) and other psychiatric disorders, particularly
      immune dysregulation or inflammation, oxidative stress, mitochondrial dysfunction
      and environmental toxicant exposures ('four major areas'). The aim of this study
      was to determine trends in the literature on these topics with respect to ASD. A
      comprehensive literature search from 1971 to 2010 was performed in these four
      major areas in ASD with three objectives. First, publications were divided by
      several criteria, including whether or not they implicated an association between
      the physiological abnormality and ASD. A large percentage of publications
      implicated an association between ASD and immune dysregulation/inflammation (416
      out of 437 publications, 95%), oxidative stress (all 115), mitochondrial
      dysfunction (145 of 153, 95%) and toxicant exposures (170 of 190, 89%). Second,
      the strength of evidence for publications in each area was computed using a
      validated scale. The strongest evidence was for immune dysregulation/inflammation
      and oxidative stress, followed by toxicant exposures and mitochondrial
      dysfunction. In all areas, at least 45% of the publications were rated as
      providing strong evidence for an association between the physiological
      abnormalities and ASD. Third, the time trends in the four major areas were
      compared with trends in neuroimaging, neuropathology, theory of mind and genetics
      ('four comparison areas'). The number of publications per 5-year block in all
      eight areas was calculated in order to identify significant changes in trends.
      Prior to 1986, only 12 publications were identified in the four major areas and
      51 in the four comparison areas (42 for genetics). For each 5-year period, the
      total number of publications in the eight combined areas increased progressively.
      Most publications (552 of 895, 62%) in the four major areas were published in the
      last 5 years (2006-2010). Evaluation of trends between the four major areas and
      the four comparison areas demonstrated that the largest relative growth was in
      immune dysregulation/inflammation, oxidative stress, toxicant exposures, genetics
      and neuroimaging. Research on mitochondrial dysfunction started growing in the
      last 5 years. Theory of mind and neuropathology research has declined in recent
      years. Although most publications implicated an association between the four
      major areas and ASD, publication bias may have led to an overestimation of this
      association. Further research into these physiological areas may provide insight
      into general or subset-specific processes that could contribute to the
      development of ASD and other psychiatric disorders.

PMID- 22143007
TI  - Overcoming the spatial barriers of the stimulus secretion cascade in pancreatic
      beta-cells.
AB  - The ability of the pancreatic beta-cells to adapt the rate of insulin release in
      accordance to changes in circulating glucose levels is essential for glucose
      homeostasis. Two spatial barriers imposed by the plasma membrane and inner
      mitochondrial membrane need to be overcome in order to achieve stringent coupling
      between the different steps in the stimulus-secretion cascade.   The first
      spatial barrier is overcome by the presence of a glucose transporter (GLUT) in
      the plasma membrane, whereas a low affinity hexokinase IV (glucokinase, GK) in
      the cytosol conveys glucose availability into a metabolic flux that triggers and
      accelerates insulin release. The mitochondrial inner membrane comprises a second
      spatial barrier that compartmentalizes glucose metabolism into glycolysis
      (cytosol) and tricarboxylate (TCA) cycle (mitochondrial matrix). The exchange of
      metabolites between cytosol and mitochondrial matrix is mediated via a set of
      mitochondrial carriers, including the aspartate-glutamate carrier (aralar1),
      alpha- ketoglutarate carrier (OGC), ATP/ADP carrier (AAC), glutamate carrier
      (GC1), dicarboxylate carrier (DIC) and citrate/isocitrate carrier (CIC). The
      scope of this review is to provide an overview of the role these carriers play in
      stimulus-secretion coupling and discuss the importance of these findings in the
      context of the exquisite glucose responsive state of the pancreatic beta-cell. 

PMID- 22143008
TI  - Attempts by one local health department to provide only essential public health
      services:  a 10-year retrospective case study.
AB  - BACKGROUND: Because of local political circumstances, in 1996, the local public
      health department in Amarillo, Texas, divested itself of almost all personal
      health services and chose to retain only essential population-based public health
      services. METHODS: We analyzed function, funding, and staffing for various health
      department activities in FY 1997 and again in FY 2007. The figures were adjusted
      for inflation and population growth. We interviewed key personnel about the
      motivation and effects of the changes that occurred with this 10-year period.
      RESULTS: The local health department both transferred and reassumed some personal
      health services during this period. This was primarily in the area of
      immunization services and care for special population such as refugees. Public
      health preparedness also became a significant new area of activity. Most personal
      health services provided by the health department before 1996 remained the
      function of other health care entities in the community. When adjusted for
      inflation and population growth, most of the growth in the health department's
      personnel and budget was the result of state and federally mandated program
      changes. CONCLUSIONS: Growth in this local health department, which was committed
      to provide only essential health services, was driven primarily by state and
      federally mandated programs. Real growth for essential public health services did
      not occur over a 10-year period.

PMID- 22143009
TI  - Renal denervation in resistant hypertension: radiofrequency ablation and chemical
      denervation.

PMID- 22143010
TI  - Anaesthesia for cardioversion: a prospective randomised comparison of propofol
      and etomidate combined with fentanyl.
AB  - INTRODUCTION: External electrical cardioversion is mostly performed solely under
      sedatives or hypnotics, although the procedure is painful. The aim of this
      prospective randomised study was to compare two anaesthetic protocols that
      included analgesia. METHODS: Patients with persistent atrial fibrillation were
      randomised to receive intravenously either fentanyl 50 MUg and propofol 0.5 mg/kg
      (group P) or fentanyl 50 MUg and etomidate 0.1 mg/kg (group E), while breathing
      spontaneously 100% oxygen. In the case of inadequate anaesthesia, repeated doses
      of 20 mg propofol (group P) or 4 mg etomidate (group E) were given as often as
      necessary until loss of eyelid reflex. Cardioversion was achieved with an
      extracardiac biphasic electrical shock ranging from 200 to 300 J, performed three
      times at most. RESULTS: Forty-six patients (25 in group P, 21 in group E), aged
      64 +/- 9 years, were enrolled in the study. There were no differences between the
      study groups concerning left ventricular ejection fraction, the dimension of the
      left atrium, the number of shocks needed or the number of unsuccessful
      cardioversions. Patients in group E had a shorter time from injection of the
      induction agents until loss of consciousness (49 vs. 118 s, p=0.003) and until
      the first shock was given (61 vs. 135 s, p=0.004). Systolic blood pressure
      decreased significantly (repeated measurements ANOVA with Bonferroni adjustment)
      in group P when the baseline value was compared to that after anaesthesia
      induction (mean decrease 15.2 mmHg, 95% CI 5.6-24.8 mmHg, p=0.001) and to the
      value after recovery (mean decrease 15.2 mmHg, 95% CI 4.8-25.7 mmHg, p=0.002).
      Manual ventilation was required in 7 and 9 patients in groups P and E,
      respectively (p=0.360). CONCLUSION: Both anaesthetic regimens provided excellent
      conditions for external electric cardioversion. In addition, etomidate in
      combination with fentanyl had a shorter induction time and ensured haemodynamic
      stability.

PMID- 22143011
TI  - Marked troponin elevation after implantation of a permanent antibradycardia
      pacemaker.
AB  - INTRODUCTION: Transvenous insertion of endocardial leads for permanent pacing is
      often accompanied by minor myocardial damage, detected thanks to the high
      sensitivity of cardiac troponins. It is unknown whether higher troponin levels,
      commensurate with more severe myocardial damage, can be encountered after
      implantation procedures. METHODS: Over a 3-year period, 283 patients underwent an
      implantation of a full antibradycardia pacemaker system (pulse generator plus
      leads). Patients were required to have normal levels of cardiac troponin I (CTNI)
      on a venous blood sample taken immediately prior to elective pacemaker insertion.
      Post implantation CTNI levels were measured in all patients 6 hours after the
      procedure. Repeated samples were taken if high CTNI levels were found at 6 hours.
      RESULTS: Elevated CTN-I levels were found in 167 patients (59%, 95% CI: 0.53
      0.64), but only 5 of them (1.8%, 95% CI=0.8 to 4.1%) had peak CTN-I levels far
      exceeding the range of minimal myocardial damage (i.e. CTN-I >1.5 ng/ml).
      Implantation of the devices was successful in all patients and we did not observe
      any complications. None had clinical evidence of an acute coronary event before
      or during the pacemaker implantation procedure and coronary angiography revealed
      no significant lesions in the coronary arteries. CONCLUSIONS: CTN-I elevations
      after pacemaker implantation may far exceed levels corresponding to minimal
      myocardial damage. This should be a matter of concern, especially if an early
      discharge is planned after pacemaker implantation.

PMID- 22143012
TI  - Systemic inflammatory response syndrome after extracorporeal circulation: a
      predictive algorithm for the patient at risk.
AB  - INTRODUCTION: Perioperative systemic inflammatory response syndrome (SIRS)
      remains a catastrophe in cardiac surgery and adequate patient screening is still
      lacking. We present a prospective trial starting with preoperative data
      collection. For the first time, the postoperative outcomes of patients after open
      heart surgery are evaluated to predict a hazard-constellation for the patient at
      risk of developing SIRS. METHODS: Of 2315 patients undergoing cardiac surgery
      over a 2-year period, 107 were considered likely to develop perioperative SIRS
      based on a high-risk stratification; 12 of them actually developed SIRS and were
      recruited for this study. Another 20 uneventful consecutive patients served as
      controls. Blood samples were collected from before the induction of anaesthesia
      until the morning of the second postoperative day and were analysed for
      complement, cytokines, adhesion-molecules, endothelin-1 (ET-1), plasminogen
      activatorinhibitor (PAI), the coagulation and fibrinolysis cascade and routine
      laboratory analysis. RESULTS: Significant preoperative differences were observed
      in leukocytes, lymphocytes, alkaline phosphatase,ICAM-3 and VCAM-1 (p<0.05).
      Significant positive correlations were found for ET-1 and lactate in the SIRS
      group. The increase in these parameters was correlated with a prolonged duration
      of extracorporeal circulation. The best predictive combination for SIRS consisted
      of alkaline phosphatase, ET-1, ICAM-1, -2, -3, VCAM-1 and ELAM-1. CONCLUSIONS:
      The results suggest a new theory regarding the development of perioperative SIRS.
      It is not the extracorporeal circulation itself that represents the main trigger,
      but rather an a priori activation of the endothelial cells, lymphocytes and
      leukocytes. This activation impairs the microcirculation and finally leads to
      multi-organ failure. The current data allow the identification of the patient at
      risk and can thus influence the individual operative schedule.

PMID- 22143013
TI  - The contegra(r) valved heterograft conduit for right ventricular outflow tract
      reconstruction: a reliable solution.
AB  - INTRODUCTION: The Contegra(r) bioprosthetic valved conduit, a glutaraldehyde
      preserved valve-containing bovine jugular vein graft (Contegra, Medtronic Inc.,
      Minneapolis MN, USA) introduced for clinical trials in 1998, is used for
      reconstruction of the right ventricular outflow tract (RVOT), mainly in children.
      This study evaluates our surgical experience with the Contegra(r) graft,
      emphasizing the assessment of conduit durability at mid-term follow up. METHODS:
      The intermediate results of RVOT reconstruction utilizing the Contegra conduit
      were retrospectively analyzed in a series of 34 consecutive patients (25 male, 9
      female), with a mean age of 10.9 +/- 11.2 years (range 0.2-46 years). Included
      were 14 patients with tetralogy of Fallot (TOF) with pulmonary atresia, 11 with
      reoperation of previously corrected TOF, 5 with truncus arteriosus, 2 with TOF
      with absent pulmonary valve, 1 reoperation of previously repaired double outlet
      right ventricle with pulmonary atresia, and 1 undergoing a Ross procedure.
      Contegra conduit sizes varied in diameter between 12 and 22 mm (mean 18.3 +/- 3.2
      mm). RESULTS: There were no hospital deaths. There was one early conduit
      replacement as a result of recurrent thrombosis. Four patients developed early
      thrombus formation in a valve cusp with complete resolution following
      anticoagulation therapy. At mean follow up of 85 months (range 6-136 months) and
      median follow up of 95 months, one patient required Contegra graft explantation
      in another institution (indications unknown). Freedom from reoperation for
      Contegra grafts was 94% at 11.4 years. Mean transpulmonary pressure gradients
      remained low (9.6 +/- 5.3 mmHg postoperative, 19.6 +/- 10.6 mmHg at follow up).
      Although there was a clear trend towards worsening of conduit valve
      insufficiency, this was neither statistically significant nor considered
      clinically so. CONCLUSIONS: In our experience of 34 consecutive operations, the
      Contegra(r) valved conduit for RVOT reconstruction seems to be a reliable
      alternative to homograft conduits, with promising mid-term freedom from
      structural deterioration and reoperation.

PMID- 22143015
TI  - Stable coronary artery disease: latest data in the battle between conservative
      and invasive management.

PMID- 22143014
TI  - Oral antiplatelet agents and chronic kidney disease.

PMID- 22143016
TI  - Ventricular arrhythmias: from the electrophysiology laboratory to clinical
      practice. Part I: malignant ventricular arrhythmias.

PMID- 22143017
TI  - Multimodality imaging of a myocardial infarction culprit lesion.

PMID- 22143018
TI  - Coronary artery aneurysm can occur in drug eluting stents: is plaque composition
      important?

PMID- 22143019
TI  - Acute rupture of a fibromuscular dysplasia related renal artery aneurysm:
      emergency treatment with a covered stent.
AB  - We report the successful exclusion of a ruptured left renal artery aneurysm as a
      first presentation of fibromuscular dysplasia in a haemodynamically unstable 57
      year-old man. The aneurysm was repaired in an emergency setting by deployment of
      a covered stent with a satisfactory result. Follow-up computed tomography
      confirmed successful exclusion of the aneurysm. A renal artery branch originating
      from the aneurismal sac was sacrificed with subsequent regional infarction. Our
      experience shows that the use of a covered stent is an effective, quick and life
      saving procedure in a ruptured renal artery aneurysm.

PMID- 22143020
TI  - Emergency intervention for unprotected left main coronary artery stenosis: case
      report and review of the literature.
AB  - Left main coronary artery stenosis is an important cause of symptomatic coronary
      artery disease, although relatively infrequent. The current guidelines recommend
      coronary artery bypass grafting as the first line treatment and standard of care,
      but percutaneous coronary intervention is likely to lead to faster reperfusion of
      coronary flow, avoiding the delays of a major surgical intervention. Our patient
      overcame cardiogenic shock after the flow of the left main coronary artery was
      rapidly restored through percutaneous coronary intervention and 6 days later,
      when hemodynamically stable, he underwent elective coronary artery bypass graft
      surgery. One year after the intervention, the patient has a normal functional
      status and an ejection fraction of 52%. This result is compatible with several
      small studies showing that percutaneous coronary intervention in left main
      coronary artery occlusions is feasible and effective, with a good short- and mid
      term prognosis.

PMID- 22143021
TI  - Non-invasive assessment may have a key role in follow-up performance of modified
      Cabrol aortic root reconstruction.
AB  - Surgical repair of ascending aortic disease involving the aortic root most
      commonly involves the direct ana stomosis of the coronary ostia to the composite
      aortic graft. Occasionally, when direct aortocoronary ana stomosis is not safe or
      technically challenging--such as in cases of extreme aortic dilatation,
      calcification and reoperations--the Cabrol technique and its modification can
      provide a safe and effective alternative. As the Cabrol is often reserved as a
      second line or bailout procedure, there is insufficient evidence to support the
      optimal imaging assessment and follow up of patients who have undergone this
      complex aortic recon struction. We present the case of a patient where emergency
      replacement of the aortic root took place with a modified Cabrol aortocoronary
      anastomosis. We discuss the usefulness, findings and limitations of modern
      noninvasive imaging modalities that can provide a complete functional and
      anatomical assessment of this surgical technique.

PMID- 22143023
TI  - Cardiovascular magnetic resonance in Greece: ready for prime time?

PMID- 22143022
TI  - Real-time polymerase chain reaction seems not to be superior to blood cultures in
      anticipating valve sterilization in infective endocarditis.

PMID- 22143024
TI  - Greek cardiovascular medicine in 2012 and beyond: the near future and lessons
      from the recent past.

PMID- 22143025
TI  - Influence of surface characteristics on biofouling formed on polymers exposed to
      coastal sea waters of India.
AB  - Biofouling on six different (silicone rubber, polydimethylsiloxane,
      polypropylene, high density polyethylene, polyvinylchloride, and polycarbonate)
      substrata with varying surface energy (18-40 mN/m) and surface roughness (R(a) 45
      175 MUm) was studied in the Eastern coastal waters of India over a short period
      of time (3 days). The results showed that the substrata surface energy (SE)
      followed by the surface roughness (R(a)) had profound effect on attachment of
      fouling organisms. After one day of immersion, viable count of bacteria in the
      biofilm was positively correlated with surface energy (r=0.69, p<0.05) and not
      with surface roughness (r=-0.02) of the substratum. Whereas, Pseudomonas count
      was inversely correlated with surface energy (r=-0.66, p<0.05) and surface
      roughness (r=-0.52, p<0.05). The attachment of macrofouler and the surface
      characteristics were also well correlated with SE 0.48 and with roughness 0.62,
      p<0.05. A positive correlation was observed amongst the various biofouling
      constituents such as bacteria, ATP, carbohydrates and organic matter on almost
      all the substrata. However after the first day, the surface characteristics of
      the substratum became less important and the conditioning film that was formed on
      the substrata appeared to directly influence further fouling on the surfaces, as
      evidenced by poor correlation between surface energy and macrofouler attachment
      (r=-0.11). The observation of high numbers of Hydroides elegans on PVC could be
      solely due to the influence of surface roughness (r=0.62). Though there is no
      marked difference in the 'primary film', and the composition of the biofilm, the
      amount of attached macrofouler is minimal on silicone rubber and
      polydimethylsiloxane on subsequent days of immersion, which reveals the foul
      release quality of these substrata probably due to their flexible nature.

PMID- 22143026
TI  - Polyoxazoline adsorption on silica nanoparticles mediated by host-guest
      interactions.
AB  - The objective of this work is to develop an original method of polyoxazoline
      brush generation based on supramolecular chemistry onto silica nanoparticles. A
      first layer is realized by adsorption of a polymer bearing beta-cyclodextrin
      units (PbetaCD). This allows the anchoring of a second layer made of alkyl end
      capped poly(2-methyl-2-oxazoline) (POXZ-C(n)) via host-guest interactions between
      the alkyl end groups and the beta-cyclodextrin units. The characteristics of the
      surface layers were studied by dynamic light scattering. A first study of PbetaCD
      adsorption allowed to define the conditions of homogeneous PbetaCD coverage onto
      the silica surfaces. Then the adsorption of the second polymer onto the PbetaCD
      coated nanoparticles was studied as a function of the POXZ-C(n) solution
      concentration. Brush layers with chains in extended conformation could be
      obtained above a critical POXZ-C(n) concentration. The large thickness
      sensitivity to the feeding POXZ-C(n) concentrations allowed to show that the POXZ
      C(n) grafting ratio can be controlled by the POXZ-C(n) concentrations. In a
      limited concentration range, the nature of the anchoring end-group (C(12) or
      C(18)) does not influence the shape of the POXZ layer.

PMID- 22143027
TI  - Modulation of graft architectures for enhancing hydrophobic interaction of
      biomolecules with thermoresponsive polymer-grafted surfaces.
AB  - This paper describes the effects of graft architecture of poly(N
      isopropylacrylamide) (PIPAAm) brush surfaces on thermoresponsive aqueous
      wettability changes and the temperature-dependent hydrophobic interaction of
      steroids in silica capillaries (I.D.: 50 MUm). PIPAAm brushes were grafted onto
      glass substrates by surface-initiated atom transfer radical polymerization (ATRP)
      that is one of the living radical polymerization techniques. Increases in the
      graft density and chain length of PIPAAm brushes increased the hydration of
      polymer brushes, resulting in the increased hydrophilic properties of the surface
      below the transition temperature of PIPAAm at 32  degrees C. More hydrophobic
      surface properties were also observed on surfaces modified with the block
      copolymers of IPAAm and n-butyl methacrylate (BMA) than that with IPAAm
      homopolymer-grafted surfaces over the transition temperature. Using PBMA-b-PIPAAm
      grafted silica capillaries, the baseline separation of steroids was successfully
      achieved by only changing temperature. The incorporation of hydrophobic PBMA
      chains in grafted PIPAAm enhanced the hydrophobic interaction with testosterone
      above the transition temperature. The surface modification of hydrophobicity
      enhanced thermoresponsive polymers is a promising method for the preparation of
      thermoresponsive biointerfaces that can effectively modulated their biomolecule
      and cell adsorption with the wide dynamic range of hydrophilic/hydrophobic
      property change across the transition temperature.

PMID- 22143028
TI  - Abstracts of the 8th Annual ENETS (European Neuroendocrine Tumor Society)
      Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease. March
      9-11, 2011. Lisbon, Portugal.

PMID- 22143029
TI  - Valproic acid-mediated neuroprotection in retinal ischemia injury via histone
      deacetylase inhibition and transcriptional activation.
AB  - Retinal ischemia plays a central role in several retinal diseases. The
      pathogenesis of retinal ischemia involves changes in gene expression. Valproic
      acid (VPA), a broad-spectrum histone deacetylase inhibitor, is an anticonvulsant
      and mood-stabilizing drug with neuroprotective effects. Here, we investigated
      whether VPA protects the retina and optic nerve axon from ischemic damage in a
      rat model and determined a possible protective mechanism. Adult male Wistar rats
      were randomized into sham, ischemia/reperfusion (I/R)-plus-vehicle, and I/R-plus
      VPA groups. Rats received subcutaneous injections of 300 mg/kg VPA or phosphate
      buffered saline twice a day after retinal ischemia induced by acute high
      intraocular pressure. Twenty-four hours after I/R, retinal neuron apoptosis was
      evaluated using the TUNEL assay. The expression of heat-shock protein 70 (Hsp70),
      activated-caspase-3, and apoptotic-protease-activating factor-1 (apaf-1),
      acetylation levels of histone H3, release of cytochrome c, and interaction
      between Hsp70 and apaf-1 were analyzed by immunoblotting analysis in all groups;
      the transcriptional activation of the Hsp70 gene and interaction between the
      Hsp70 promoter with p300 or HDAC1 were analyzed using chromatin
      immunoprecipitation assay. Seven days after I/R, the histological changes in the
      retina were evaluated using hematoxylin and eosin staining, and optic nerve axon
      damage was evaluated using toluidine blue staining and transmission electron
      microscopy. The density of retinal ganglion cells (RGCs) was analyzed using
      Fluoro-Gold retrograde labeling at 7, 14, 21 days after I/R. VPA markedly
      attenuated I/R-induced retinal neuron apoptosis, damage to RGCs, and
      morphological injury to the retina and optic nerve axons. VPA resulted in the
      upregulation of Hsp70 and hyperacetylation of histone H3, accompanied by Hsp70
      promoter hyperacetylation, which may result from increased p300 recruitment to
      the Hsp70 promoter. Furthermore, VPA increased the binding between Hsp70 and apaf
      1 to block apoptosome formation and reduced the release of cytochrome c and
      activation of caspase-3 in the retina after I/R. Therefore, VPA-mediated
      neuroprotection against I/R injury in the retina may involve cytoprotective Hsp70
      induction via transcriptional activation and inhibition of the mitochondria
      mediated apoptosis pathway.

PMID- 22143030
TI  - Anticoagulation of diethyl citrate and its comparison with sodium citrate in an
      animal model.
AB  - AIMS: To improve the side effects caused by sodium citrate (Na(3)Cit), the
      anticoagulant effects of diethyl citrate (Et(2)Cit) were investigated. METHODS:
      The in vitro anticoagulant effects and dissociation capacity of the chelate of
      Et(2)Cit with calcium ions were compared with those of Na(3)Cit in rabbits.
      RESULTS: The activated coagulation time test showed that blood clotting time
      exceeded 1,200 s when the concentrations of Et(2)Cit and Na(3)Cit were greater
      than 87.2 and 8.72 mmol/l, respectively. The concentrations of free calcium ions
      in blood c(Ca(2+)) were reduced when Et(2)Cit was injected into the rabbits.
      CONCLUSIONS: Et(2)Cit reduces the concentration of ionized Ca(2+) in blood and
      has anticoagulant effects. The dissociation of the chelate of Et(2)Cit with
      Ca(2+) was faster than that of Na(3)Cit with Ca(2+) within 10 min after
      injection. The recovery speed of blood calcium concentration with Et(2)Cit was
      more rapid than that with Na(3)Cit. The findings show that Et(2)Cit prevents
      hypocalcemia.

PMID- 22143031
TI  - Directions and opportunities for immunoprophylaxis development among Polish Army
      soldiers sent to foreign missions.
AB  - The Polish Army is engaged in stabilization activities and peace missions in
      countries often characterized by completely different customs, culture and
      religion, as well as different bacterial and viral flora. It might be expected
      that foreign military operations will be more and more important, as the number
      of local conflicts is escalating. The safety and health of our citizens in these
      circumstances is the absolute priority. This article is dedicated to the safety
      of soldiers in the context of the risks associated with infectious diseases that
      can be prevented by vaccination. The main goal of this study is to verify the
      model and condition of immunization in the Polish Army in the context of foreign
      contingents, as well as presentation of the possibilities to optimize solutions
      in this field.

PMID- 22143032
TI  - Characterization and expression analysis in the developing embryonic brain of the
      porcine FET family: FUS, EWS, and TAF15.
AB  - The FET protein family consists of FUS (TLS), EWS (EWSR1), and TAF15. The FET
      proteins bind DNA and RNA and are involved in transcriptional regulation and RNA
      processing. Translocations involving the FET genes have been identified in human
      sarcomas, and mutations in the FUS and TAF15 genes are associated with
      Amyotrophic Lateral Sclerosis. We here describe the characterization of the
      porcine FET proteins and an expression analysis during embryonic brain
      development. The FET proteins are well conserved between pig and human. FET
      protein mutations associated with Amyotrophic Lateral Sclerosis affect
      evolutionary conserved amino acids. In cultured cells the porcine FET proteins
      have a nuclear localization with some specific cytoplasmic aggregation of TAF15
      in neuronal progenitor cells. Immunohistochemical analyses supported a
      predominant nuclear localization, but also faint cytoplasmic localization. The
      FET proteins have similar expression profiles throughout the development of the
      embryonic porcine brain and most cell types appeared positive for expression.
      Quantitative RT-PCR analyses showed that the FET mRNA expression decreased during
      embryonic development of hippocampus and for FUS and EWS during embryonic
      development of cortex. FET mRNA expression was relatively constant in brain stem,
      basal ganglia, and cerebellum. Overall the FET protein localization and mRNA and
      protein expression analyses were concordant with previous analysis from the human
      brain. The presented results indicate that the porcine brain could be an
      alternative model for the future examination of the normal functions as well as
      neurological disease associated functions of the FET proteins.

PMID- 22143033
TI  - Characterisation of 13 glutamate receptor-like genes encoded in the tomato genome
      by structure, phylogeny and expression profiles.
AB  - Glutamate receptor-like genes (GLRs) are intimately associated with plant
      development, defence responses and signalling pathways. Structural and expression
      analyses of SlGLRs were performed to better characterise their roles in fruit
      development and metabolism. Utilising recently released tomato genomic sequence
      data, 15 GLRs were identified in the tomato genome (SlGLRs). Thirteen of these
      genes were represented by full-length sequences. Phylogenetic analysis of the
      SlGLRs and the AtGLRs indicates the occurrence of a tomato-specific clade (Clade
      I) that may have diverged prior to the evolving of other clades. Among the Clade
      II genes, five (SlGLR2.1, SlGLR2.2, SlGLR2.3, SlGLR2.4, and SlGLR2.5) were
      located proximally on chromosome 6, indicating possible gene duplication events.
      The expression level of four of these genes was low in all analysed samples.
      However, SlGLR2.2 expression level was notably higher, indicating that this gene
      may be functionally important. The results of this study may provide clues to the
      functions of the SlGLRs and enable future detailed characterisations of each
      gene.

PMID- 22143034
TI  - Identification and expression pattern of ribosomal L5 gene in common wheat
      (Triticum aestivum L.).
AB  - The full-length cDNA sequence (1158 bp) encoding a ribosomal L5 protein,
      designated as TaL5, was firstly isolated from common wheat (Triticum aestivum L.)
      using the rapid amplification of cDNA ends method (RACE). The open reading frame
      (ORF) of TaL5 gene was 906 bp, and its deduced amino acid sequence (301 residues)
      shared high similarity to those of other higher plant L5 proteins. TaL5 protein
      contained a putative 5S binding region (74 amino acids). TaL5 DNA sequence was
      further cloned, and sequence analysis showed that it contained 7 introns and 8
      exons. Predicated using TargetP software, TaL5 protein was putatively located in
      mitochondria and contains a transit peptide of 12 amino acids. During grain
      filling period, temporal expression pattern of TaL5 gene was approximately
      consistent with the rates of starch accumulation in grains. Additionally, TaL5
      gene was dramatically induced by salt, drought and freezing stresses, exogenous
      abscisic acid (ABA) and salicylic acid (SA) in wheat seedlings. These implied
      that TaL5 gene could function in growth, development and abiotic stresses in
      wheat plants.

PMID- 22143035
TI  - Expression of synthetic human tumor necrosis factor is toxic to Escherichia coli.
AB  - The overlap forward-primer-walk polymerase chain reaction method was used to
      synthesize the human tumor necrosis factor alpha (hTNF) gene in Escherichia coli
      cells. Growth curves for hTNF and pET23d vector cultures exhibited slower
      doubling rates than cultures containing the pET23d vector alone. Cell cultures
      transformed with hTNF reached peak densities (0.4-0.6 OD(600)) 3 to 4 h post
      induction, then decreased prior to growth recovery. This inhibition occurred in
      the BL21DE3 strain of E. coli, whereas no inhibition of growth and no expression
      of hTNF were observed in the JM109 strain of E. coli containing hTNF. Induced
      hTNF cultures hyperexpressed the hTNF-histidine fusion protein for the first 3 to
      4h of induction; subsequently, growth retardation was observed. Hyperexpression
      and continuous growth were observed in the extracellular expression system.
      Electron microscopy revealed that accumulation of hTNF inclusion bodies was
      apparent only in the intracellular expression system - no accumulation was
      observed with regard to the secretory system. The hTNF-pET23d vector was purified
      from cells expressing the fusion protein and from cells with recovered growth
      curves. Sequencing of the vector demonstrated the complete hTNF gene and T7
      promoter in cells expressing the fusion protein and mutations of the T7 promoter
      site from recovered cells.

PMID- 22143036
TI  - The association between IFN-gamma and IL-4 genetic polymorphisms and childhood
      susceptibility to bronchial asthma.
AB  - The present study aims to investigate the association between the genetic
      polymorphisms of interferon (IFN)-gamma and interleukin (IL)-4 with childhood
      susceptibility to asthma and the levels of IFN-gamma, IL-4, and immunoglobulin
      (Ig) E among asthmatic children. A total of 100 asthmatic children and 122
      control children were enrolled in the present study. The genotypes of the IFN
      gamma gene at the -179G/T locus and the IL-4 gene at the -33C/T and -589C/T loci
      were detected using polymerase chain reaction with restriction fragment length
      polymorphism. The IFN-gamma gene at the +874A/T locus and the IFN-gamma CA
      repeats were tested using allele-specific and capillary electrophoresis,
      respectively, whereas the IFN-gamma, IL-4, and total IgE levels were measured
      using enzyme-linked immunosorbent assays. The 100 asthmatic children and the 122
      control children were all GG homozygous in the -179 locus of the IFN-gamma gene,
      which shows that the IFN-gamma gene is not mutated at the -179 locus. No
      significant differences were found in terms of genotypic and allelic frequency
      distribution in the IFN-gamma gene or the CA repeat at the +874A/T locus between
      the asthmatic children and the control (P>0.05). An association was found between
      the polymorphism of the IFN-gamma gene at +874A/T and IFN-gamma levels. IFN-gamma
      expression was lower among patients with the AA genotype than those with the AT
      genotype (P<0.05); the genotypic and allelic frequency distributions of the IL-4
      gene at -33C/T and -589C/T were significantly different between the asthmatic
      children and the control (P<0.05). The levels of IL-4 and IgE among children with
      TT genotype at the -33 and -589 loci were higher than those with the CT genotype,
      but only the polymorphism at -33C/T was associated with IL-4 levels (P<0.05). The
      polymorphisms of the IFN-gamma gene at +874A/T or the CA repeats are not
      correlated with susceptibility to asthma. Thus, the polymorphism at +874A/T is
      correlated with IFN-gamma level. The TT genotypes of the IL-4 gene at the -33 and
      -589 loci are associated with asthma susceptibility in children, and polymorphism
      at the -33 locus may be associated with IL-4 level.

PMID- 22143037
TI  - A new typing technique for the Rickettsiales Ehrlichia ruminantium: multiple
      locus variable number tandem repeat analysis.
AB  - Ehrlichia ruminantium (ER) is a member of the order Rickettsiales transmitted by
      Amblyomma ticks. This obligatory intracellular bacterium is the causative agent
      of a fatal disease in ruminants, named heartwater. It represents a constraint on
      breeding development in sub-Saharan Africa and in the Caribbean. The genetic
      diversity of the strains of ER, which could be a limiting factor to obtain
      effective vaccines, needs to be better characterized. For this purpose, we
      developed a molecular typing technique based on the polymorphism of variable
      number tandem repeat (VNTR) sequences, MLVA (multiple locus VNTR analysis). Eight
      (out of 21) VNTR candidates were validated using 17 samples representing a panel
      of ER strains from different geographical origins from West, South Africa, and
      Caribbean areas and in ER infected ticks and goat tissues. This result
      demonstrated the ability of these VNTRs to type a wide range of strains. The
      stability of the selected VNTR markers was very good, at the time scale needed
      for epidemiological purposes: in particular, no difference in the VNTR profiles
      was observed between virulent and attenuated strains (for Gardel and Senegal
      strains) and between strains (Gardel and Blonde strains) isolated in the same
      area 19years apart. We validated the strong discriminatory power of MLVA for ER
      and found a high level of polymorphism between the available strains, with 10
      different profiles out of 13 ER strains. The MLVA scheme described in this study
      is a rapid and efficient molecular typing tool for ER, which allows rapid and
      direct typing of this intracellular pathogen without preliminary culture and
      gives reliable results that can be used for further epidemiological studies.

PMID- 22143038
TI  - Distinct development of the cerebral cortex in platypus and echidna.
AB  - Both lineages of the modern monotremes have distinctive features in the cerebral
      cortex, but the developmental mechanisms that produce such different adult
      cortical architecture remain unknown. Similarly, nothing is known about the
      differences and/or similarities between monotreme and therian cortical
      development. We have used material from the Hill embryological collection to try
      to answer key questions concerning cortical development in monotremes. Our
      findings indicate that gyrencephaly begins to emerge in the echidna brain shortly
      before birth (crown-rump length 12.5 mm), whereas the cortex of the platypus
      remains lissencephalic throughout development. The cortices of both monotremes
      are very immature at the time of hatching, much like that seen in marsupials, and
      both have a subventricular zone (SubV) within both the striatum and pallium
      during post-hatching development. It is particularly striking that in the
      platypus, this region has an extension from the palliostriatal angle beneath the
      developing trigeminoreceptive part of the somatosensory cortex of the lateral
      cortex. The putative SubV beneath the trigeminal part of S1 appears to
      accommodate at least two distinct types of cell and many mitotic figures and
      (particularly in the platypus) appears to be traversed by large numbers of
      thalamocortical axons as these grow in. The association with putative
      thalamocortical fibres suggests that this region may also serve functions similar
      to the subplate zone of Eutheria. These findings suggest that cortical
      development in each monotreme follows distinct paths from at least the time of
      birth, consistent with a long period of independent and divergent cortical
      evolution.

PMID- 22143039
TI  - Gender differences in health-related quality of life among cannabis users:
      results from the National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - BACKGROUND: Cannabis is the most widely used illicit substance worldwide. The aim
      of the present study was to assess self-reported Quality of Life (QoL) among
      cannabis users in a large representative sample. METHODS: We analyzed data from
      the National Epidemiological Survey of Alcohol and Related Conditions (NESARC,
      n=43,093). Health-related QoL was assessed using the Short-form 12-item Health
      Survey (SF-12). The contribution of cannabis use and cannabis use disorders (CUD)
      to SF-12 scores was assessed using multiple linear regressions models. RESULTS:
      The prevalence of cannabis use and CUD in the last 12 months was 4.1% and 1.5%,
      respectively. Mean SF-12 mental summary scores were significantly lower
      (indicating a lower QoL) among female and male cannabis users compared to non
      users (by 0.6 standard deviations (SD) and 0.3 SD, respectively), and among
      females and males with CUD compared to those without CUD (by 0.9 SD and 0.4 SD,
      respectively). Controlling for sociodemographic variables and mental illness,
      each joint smoked daily was associated with a greater decrease in mental QoL
      summary scores in females (0.1 SD) compared to males (0.03 SD). CONCLUSIONS:
      Cannabis use and CUD were associated with lower self-reported mental QoL.
      Specifically, our findings showed that cannabis use and CUD have a more
      significant effect on self-reported mental health QoL among female users.
      Assessing severity of cannabis use and impact of CUD should take into account
      functional and emotional outcomes. This may particularly aid in detecting the
      impact of cannabis use and CUD on mental health-related QoL among females.

PMID- 22143040
TI  - Social-cultural factors in end-of-life care in Belgium: a scoping of the research
      literature.
AB  - BACKGROUND: As end-of-life (EoL) care expands across Europe and the world,
      service developments are increasingly studied. The sociocultural context in which
      such changes take place, however, is often neglected in research. AIM: To explore
      sociocultural factors in EoL care in Belgium as represented by the literature.
      DESIGN: A scoping of the empirical research literature following a systematic
      search procedure with a focus on thematic analysis based on the literature
      findings. DATA SOURCES: Searches were carried out in eight electronic databases,
      five journals, reference lists, and grey literature (through September 2010).
      Articles informing about sociocultural issues in EoL care were included. RESULTS:
      One hundred and fifteen original studies met the inclusion criteria, the majority
      (107) published between 2000 and 2010. Four major themes were: Setting;
      Caregivers; Communication; and Medical EoL Decisions (the largest category).
      Minority Ethnic Groups was an emerging theme. Gaps included: research in Wallonia
      and Brussels; the role and experiences of informal caregivers; issues of access
      to palliative care; and experiences of minority ethnic groups. There was a
      paucity of in-depth qualitative studies. CONCLUSIONS: Various sociocultural
      factors influence the provision of EoL care in Belgium. This country provides a
      unique opportunity to witness how euthanasia is put into practice when legalized,
      in a context where palliative care is also highly developed and where many health
      care institutions have Catholic affiliation, providing an important example to
      others. Attention to how the sociocultural context affects EoL care adds to the
      current evidence base of service provision, which is essential in the further
      development of EoL care.

PMID- 22143041
TI  - Awareness of incurable cancer status and health-related quality of life among
      advanced cancer patients: a prospective cohort study.
AB  - BACKGROUND: Many patients near death report an interest in knowing their
      prognoses. Patients' awareness of disease status may lead to more appropriate
      care and maintained or improved quality of life. However, it is not known whether
      advanced cancer patients' awareness of disease status is associated with
      patients' quality of life. AIM: We aimed to examine the effect of patients'
      awareness of disease status on the health-related quality of life (HRQOL) among
      advanced cancer patients undergoing palliative chemotherapy. DESIGN: In this
      prospective cohort study, patients were followed-up at 4-6 weeks and 2-3 months
      after the initial palliative chemotherapy. Patients' awareness of disease status,
      and demographic and clinical characteristics were assessed at baseline, and
      depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) and
      HRQOL using the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC QLQ-C30) were assessed three times. SETTING
      / PARTICIPANTS: In total, 100 patients with advanced cancer starting palliative
      chemotherapy were recruited from two tertiary university hospitals and from the
      Korea National Cancer Center. RESULTS: Patients with advanced cancer undergoing
      palliative chemotherapy experienced deteriorated HRQOL. Of these, the patients
      who were aware of their disease status as incurable had significantly higher role
      (p=0.002), emotional (p=0.025), and social functioning (p=0.002), and lower
      fatigue (p=0.008), appetite loss (p=0.039), constipation (p=0.032), financial
      difficulties (p=0.019), and anxiety (p=0.041) compared with patients unaware of
      disease status. CONCLUSION: Our findings demonstrate the importance of patients'
      awareness of disease status to HRQOL.

PMID- 22143042
TI  - Analyzing microbial disease at high resolution: following the fate of the
      bacterium during infection.
AB  - The study of bacterial pathogens has historically been viewed with a wide lens,
      providing a picture of how bacterial populations act as groups, but with
      insufficient resolution to see how microorganisms act as individuals. For most
      bacterial pathogens, we do not know the minimal number of microbes that initiate
      infection in a particular organ site, the number that spread outside the site of
      initial colonization, and how many persist over time. Recent studies have begun
      to shed light on these points, and the development of new techniques has
      dramatically increased the ability of researchers to interrogate these problems.
      With new approaches, the field of bacterial pathogenesis is on the verge of
      understanding the role and fate of individual bacteria during infection.

PMID- 22143043
TI  - Chondrosarcomas of the cervical and cervicothoracic spine: surgical management
      and long-term clinical outcome.
AB  - STUDY DESIGN: A retrospective review study. OBJECTIVES: To estimate the clinical
      outcome of various resection protocols in patients with chondrosarcoma (CHS) at
      the challenging region of cervical and cervicothoracic spine (CCT). SUMMARY OF
      BACKGROUND DATA: It is challenging to surgically manage CHS of the spine.
      Although total en-bloc resection has proven to be an ideal treatment, this option
      is not always feasible in the spine because of the constrains of critical
      neurovascular structures in the vicinity. Lesions at the CCT region pose even
      more difficulties, and few large clinical series concerning various protocols and
      long-term outcomes of these lesions exist at present. METHODS: Fifteen patients
      with CHS at the CCT region who underwent surgical management in our institute
      were retrospectively studied. Twelve piecemeal resections and 3 en-bloc
      resections were performed. Intraoperative local chemotherapy and postoperative
      cyberknife radiotherapy were given as adjuvant therapy. Neurologic status, local
      recurrence, distant metastasis, and treatment-related complications were
      evaluated. RESULTS: The mean follow-up time was 58.7 months (median 37 mo;
      ranging from 18 to 141 mo). Local recurrence was detected in 5 of 5 cases (100%)
      treated by intracapsular piecemeal resection, and in 1 of 7 cases (14.3%) treated
      by extracapsular piecemeal resection, whereas no recurrence was found in 3 cases
      treated by en-bloc resection. Of the 6 recurrent patients, 5 died of disease 24
      to 46 months after present surgery, and the remaining patient was alive with
      disease in the final follow-up. There were no signs of recurrence in the
      remaining 9 patients. CONCLUSIONS: For CHS at the CCT region, intralesional
      piecemeal resection has a poor prognosis and should be avoided. Oncologically, en
      bloc resection remains the best form of disease management and should be the
      primary treatment of choice. For cases in which an uncontaminated en-bloc
      resection could not be achieved, the extracapsular piecemeal resection with
      adjuvant therapy including local chemotherapy and cyberknife radiotherapy is an
      effective and achievable option.

PMID- 22143044
TI  - Comparison of a fluoroscopic 3-dimensional imaging system and conventional CT in
      detection of pars fractures in the cadaveric lumbar spine.
AB  - STUDY DESIGN: Cadaveric Study. OBJECTIVE: To compare a fluoroscopic imaging
      system with computed tomography (CT) and radiographs in detection of
      spondylolysis and radiation exposure in a cadaver model. SUMMARY OF BACKGROUND
      DATA: Lumbar spondylolysis is defined as a defect or fracture of the pars
      interarticularis and occurs with or without anterior spondylolisthesis. CT scan
      is the gold standard imaging study for spondylolysis but is limited by the supine
      position, which may cause reduction of anterolisthesis and by ionizing radiation,
      which limits the frequency of follow-up scans. METHODS: Thirteen intact cadaveric
      lumbar spine segments with 26 pars were randomized to be left intact or to
      undergo simulated fracture using a 1.3 mm oscillating microsurgical saw. Fifteen
      pars underwent simulated fracture and 11 pars were left intact. Lumbar spine
      segments were imaged using plain radiographs, multiplanar fluoroscopic imaging,
      and conventional CT scan. The images were interpreted by 3 observers blinded to
      the number and location of defects. Radiation exposure and doses were recorded
      from all imaging units. RESULTS: Average radiation doses were 0.0025 mSv for each
      radiograph, 0.23 mSv (low dose) and 0.47 mSv (high dose) for fluoroscopic
      imaging, and 1.5 mSv for conventional CT imaging (pediatric dose setting).
      Evaluation of radiographs for spondylolysis had sensitivity of 98% and
      specificity of 97%. Evaluation using low-dose fluoroscopic images, high-dose
      fluoroscopic images, and CT scan images correctly identified the status of all
      pars based on multiplanar images; sensitivity and specificity were 100%. Kappa
      analysis demonstrated a value of 0.89 for radiographic interpretation indicating
      excellent agreement. Kappa values describing agreement for image interpretation
      for fluoroscopic imaging and CT scan were equal to 1.0, representing perfect
      agreement. CONCLUSIONS: Three-dimensional fluoroscopic imaging provides
      comparable diagnostic imaging with CT scan in an experimental cadaveric model of
      spondylolysis using up to 85% less radiation than conventional CT scan.

PMID- 22143045
TI  - A posterolateral approach to occipitoatlantoaxial ventral lesions: a report of
      the long-term follow-up of 23 cases.
AB  - STUDY DESIGN: A retrospective study of consecutive patient series. OBJECTIVES: To
      report a technique of odontoidectomy using a transoccipitocervical posterolateral
      approach for occipitoatlantoaxial ventral lesions in a long-term follow-up study.
      SUMMARY OF BACKGROUND DATA: Occipitoatlantoaxial malformation and old traumatic
      dislocation usually cause compression of the high cervical spinal cord from a
      variety of different directions and angles, leading to high morbidity. The main
      objective of treatment is to relieve the anteroposterior compression and to
      restore the stability of the occipitocervical region. Currently, there are 2
      approaches to perform the surgical procedure: (1) posterior decompression by
      suboccipital and occipitocervical fusion and internal fixation; and (2)
      decompression by a transoral approach to an odontoid resection. However, there
      are some short points, which need to be changed, such as the incomplete
      decompression (the former), narrow view, cerebrospinal fluid leakage, and the
      high infection rates. METHODS: From 1999 to 2006, 23 patients with
      occipitoatlantoaxial ventral lesions were treated using a transoccipitocervical
      posterolateral approach for decompression. The procedure included an expansion of
      the foramen magnum, a resection of the posterior arch of atlas, a lateral
      occipitocervical epidural exposure to the odontoid and the C2 vertebra, and an
      excision of the odontoid. Thus, an anteroposterior decompression and
      occipitocervical spinal fusion was achieved. Neurological function, daily living
      ability, and the work ability of patients were assessed in a follow-up study.
      RESULTS: A 28-year-old woman died of respiratory and circulatory failure 10 hours
      after operation. The remaining patients survived without postoperative infection.
      The neurological injury in 17 patients did not deteriorate, whereas 5 patients
      had decreased sensation in the upper limbs, and the elbow flexor muscle strength
      in 2 patients declined by 1 grade on the operation side. Short-term follow-up (3
      6 mo, 22 cases) indicated that 19 patients recovered normal sensation with
      decreased limb muscle tension. Motor function was improved by >1 grade (5
      patients with postoperative nerve injury recovered to preoperative levels or
      better). Long-term follow-up (>4 y) of 15 patients (10 patients by clinic visit
      and 5 patients by correspondence) indicated that the occipitoatlantoaxial regions
      were stable without local discomfort or loss of nerve function. Fourteen patients
      were able to care for themselves and some patients regained their ability to
      work. One patient felt no significant improvement after surgery and had no
      improvement in the quality of life. CONCLUSIONS: Transoccipitocervical
      posterolateral approach to occipitoatlantoaxial ventral lesions provides a broad
      and sterile operating field to perform anteroposterior decompression and
      occipitocervical spinal fusion simultaneously. Neurological improvement is
      significant, and the long-term follow-up results are satisfactory.

PMID- 22143047
TI  - Lateral extracavitary, costotransversectomy, and transthoracic thoracotomy
      approaches to the thoracic spine: review of techniques and complications.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: The authors review complications, as
      reported in the literature, associated with ventral and posterolateral approaches
      to the thoracic spine. SUMMARY OF BACKGROUND: The lateral extracavitary,
      costotransversectomy, and transthoracic thoracotomy techniques allow surgeons to
      access the ventral thoracic spine for a wide range of spinal disorders including
      tumor, degeneration, trauma, and infection. Although the transthoracic
      thoracotomy has been used traditionally to reach the ventral thoracic spine when
      access to the vertebral body is required, modifications to the various dorsal
      approaches have enabled surgeons to achieve goals of decompression,
      reconstruction, and stabilization through a single approach. METHODS: A
      systematic Medline search from 1991 to 2011 was performed to identify series
      reporting clinical data related to these surgical approaches. The morbidity
      associated with each approach is reviewed and strategies for complications
      avoidance are discussed. RESULTS: Four thousand six hundred seventy-seven
      articles that assessed outcomes of the approaches to the thoracic spine were
      identified; of these 31 studies that consisted of 774 patients were selected for
      inclusion. A mean complication rate of 39%, 17%, and 15% for thoracotomy, lateral
      extracavitary, and costotransversectomy, respectively, was determined. The
      thoracotomy approach had the highest reoperation (3.5%) and mortality rates
      (1.5%). The specific complications and neurological outcomes were categorized.
      CONCLUSIONS: Outcomes of the surgical approaches to the thoracic spine have been
      reported with great detail in the literature. There are limited studies comparing
      the respective advantages and disadvantages and the differences in technique and
      outcome between these approaches. The present review suggests that in contrast to
      the historical experience of the laminectomy for thoracic spine disorders, these
      alternative approaches are safe and rarely associated with neurological
      deterioration. The differences between these approaches are based on their
      complication profiles. A thorough understanding of the regional anatomy will help
      avoid approach-related complications.

PMID- 22143046
TI  - Quantitative volumetry of cement leakage in viscosity-controlled vertebroplasty.
AB  - STUDY DESIGN: This study was designed as a cohort study comparing a prospective
      sample to a historic control group. OBJECTIVE: The aim of the actual trial was to
      compare the rate of cement leakage by quantitative volumetry comparing viscosity
      controlled and non-viscosity-controlled vertebroplasty. SUMMARY OF BACKGROUND
      DATA: Percutaneous vertebroplasty (PVP) is a widespread safe and effective
      technique in the treatment of osteoporotic compression fractures and vertebral
      metastatic lesions. However, cement leakage has been identified as a problem of
      this technique. The leakage rates are reported to range from 7% to 90%. The main
      influence factor for leakage has been demonstrated to be cement viscosity.
      Assessment of appropriate injection viscosity is highly subjective and observer
      dependent. Viscosity-controlled vertebroplasty (Vertecem system) has been
      developed to objectively measure cement viscosity before injection. It introduces
      a viscosimeter to measure the actual cement viscosity before injection into the
      vertebra, and therefore may prevent leakages resulting from low-viscosity cement
      injections. Despite more than 800 Pubmed citations on PVP, there is only 1 report
      on distinct measurement of cement leakage by semiquantitative volumetry. METHODS:
      A total of 111 vertebrae in 68 patients, in which PVP was performed for
      osteoporotic fractures, were included. Thirty-seven patients (76 operated
      vertebrae) were assessed prospectively using the viscosity-controlled
      vertebroplasty. The results were compared with a retrospective group of 31
      patients (35 operated vertebrae) undergoing PVP without using a viscosimeter.
      RESULTS: : There were no significant differences between the 2 groups in the
      applied volume of cement per fractured vertebra (P=0.73). The frequency of cement
      leakage in viscosimete-assisted vertebroplasty was 42.1% and 58.3% in the
      historic group. Cement leakage into the basivertebral vein (type B), was detected
      in 6.6% with and in 11.1% without viscosimetry. CONCLUSIONS: The use of viscosity
      controlled vertebroplasty led to a decrease in the leakage rate from 58.3% to
      42.1%. Leakage into the basivertebral vein with the risk of compression of nerval
      structures was reduced to almost 50% when viscosimetry was performed. It revealed
      to be a helpful tool for more unexperienced surgeons to assess the appropriate
      viscosity for vertebroplasty.

PMID- 22143048
TI  - Functional outcomes, morbidity, mortality, and fracture healing in 26 consecutive
      geriatric odontoid fracture patients treated with posterior fusion.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate functional outcomes,
      fracture healing, complications, and mortality associated with posterior fusion
      surgery (PSF) for the management of geriatric type II odontoid fractures. SUMMARY
      OF BACKGROUND DATA: Outcomes of C1-2 fusion for geriatric odontoid fractures are
      not well defined. METHODS: Twenty-six consecutive elderly patients with type II
      odontoid fractures were treated by the same spinal surgeon at a Level-1 trauma
      center during an 8-year period. All patients had >=50% odontoid displacement and
      were treated with PSF including C1-2 (PSF group; average age, 79 y). Chart
      reviews were performed evaluating patient comorbidities, treatment complications,
      and mortality rates. At ultimate follow-up, patients had open mouth, flexion, and
      extension radiographs to assess fracture stability and healing. In addition,
      functional outcomes were assessed using Neck Disability Index (NDI), analog pain,
      and satisfaction questionnaire scores and compared with a group of 40 aged
      matched control patients (control group; average age, 79.8 y). RESULTS: The
      mortality rate was 19.2%, and major complications occurred in 27% of patients. At
      an average 13-month follow-up (range, 3-48 mo), the fracture-healing rate was
      only 33%. However, no patient had mobile odontoid nonunion or instability of the
      C1-2 articulation. NDI scores averaged 18.1 points indicating only mild residual
      disability. Pain scores were low averaging only 1.8 points. NDI and pain scores
      did not differ significantly from aged-matched controls (P = 0.16). Treatment
      satisfaction scores were high. Odontoid nonunion was not associated with
      significantly higher levels of disability or neck pain and did not affect scores
      for patient satisfaction. CONCLUSIONS: PSF for geriatric odontoid fractures is
      associated with moderately high levels of morbidity and mortality. Posttreatment
      neck pain and disability is low and does not differ significantly from aged
      matched cohorts. Odontoid fracture healing after surgical stabilization does not
      correlate with improved functional outcomes.

PMID- 22143049
TI  - Above- and below-ground methane fluxes and methanotrophic activity in a landfill
      cover soil.
AB  - Landfills are a major anthropogenic source of the greenhouse gas methane (CH(4)).
      However, much of the CH(4) produced during the anaerobic degradation of organic
      waste is consumed by methanotrophic microorganisms during passage through the
      landfill-cover soil. On a section of a closed landfill near Liestal, Switzerland,
      we performed experiments to compare CH(4) fluxes obtained by different methods at
      or above the cover-soil surface with below-ground fluxes, and to link
      methanotrophic activity to estimates of CH(4) ingress (loading) from the waste
      body at selected locations. Fluxes of CH(4) into or out of the cover soil were
      quantified by eddy-covariance and static flux-chamber measurements. In addition,
      CH(4) concentrations at the soil surface were monitored using a field-portable
      FID detector. Near-surface CH(4) fluxes and CH(4) loading were estimated from
      soil-gas concentration profiles in conjunction with radon measurements, and gas
      push-pull tests (GPPTs) were performed to quantify rates of microbial CH(4)
      oxidation. Eddy-covariance measurements yielded by far the largest and probably
      most representative estimates of overall CH(4) emissions from the test section
      (daily mean up to ~91,500MUmolm(-2)d(-1)), whereas flux-chamber measurements and
      CH(4) concentration profiles indicated that at the majority of locations the
      cover soil was a net sink for atmospheric CH(4) (uptake up to -380MUmolm(-2)d(
      1)) during the experimental period. Methane concentration profiles also indicated
      strong variability in CH(4) loading over short distances in the cover soil, while
      potential methanotrophic activity derived from GPPTs was high (v(max)~13mmolL(
      1)(soil air)h(-1)) at a location with substantial CH(4) loading. Our results
      provide a basis to assess spatial and temporal variability of CH(4) dynamics in
      the complex terrain of a landfill-cover soil.

PMID- 22143050
TI  - The enantiomers of syn-2,3-difluoro-4-aminobutyric acid elicit opposite responses
      at the GABA(C) receptor.
AB  - The conformational behaviour and GABA receptor activity of the different
      stereoisomers of 2,3-difluoro-4-aminobutyric acid are described. Two enantiomeric
      GABA(C)-active ligands are identified, one of which is an agonist while the other
      is an antagonist. The results support an existing QSAR model of the bioactive
      geometry of GABA at GABA(C).

PMID- 22143051
TI  - Noninvasive ventilation for the immunocompromised patient:  always appropriate?
AB  - PURPOSE OF REVIEW: Over the last few decades, the survival rate in critically ill
      immunocompromised patients has substantially improved, mainly because of advances
      in oncohematological treatments and management of organ dysfunctions in the ICU.
      As a result, the number of patients admitted to the ICU has rapidly grown.
      Immunocompromised patients in whom acute respiratory failure (ARF) develops often
      require mechanical ventilatory support. In these patients, noninvasive
      ventilation (NIV) has the potential of avoiding endotracheal intubation and its
      complications. This review will discuss the recent findings on the role of NIV in
      immunocompromised patients with ARF. RECENT FINDINGS: In recent studies, NIV
      success was associated with shorter periods of ventilatory assistance and ICU
      stays, less infectious complications, and lower ICU and hospital mortality,
      compared with invasive mechanical ventilation. Failure of NIV occurred in half of
      the hematological patients with ARF. Major risk factors for NIV failure in these
      patients were illness severity at baseline and the presence of acute respiratory
      distress syndrome on admission. SUMMARY: Use of NIV may not be appropriate for
      all immunocompromised patients. However, current evidence supports the use of NIV
      as the first-line approach for managing mild/moderate ARF in selected patients
      with immunosuppression of various origin.

PMID- 22143052
TI  - Imaging in acute lung injury and acute respiratory distress syndrome.
AB  - PURPOSE OF REVIEW: The review focuses on recent achievements obtained by means of
      imaging techniques in clinical and experimental studies on acute lung injury
      (ALI) and acute respiratory distress syndrome (ARDS). RECENT FINDINGS: The review
      focuses on four imaging techniques: computed tomography (CT), PET, electrical
      impedance tomography (EIT) and ultrasound, highlighting the most recent
      developments for each technique. Whereas CT and ultrasound are primarily based on
      detection of density, EIT and PET are aimed at providing more functional data.
      SUMMARY: Major improvements were recently obtained in imaging structure and
      several functions of the lungs, with the potential of positively impacting the
      clinical practice.

PMID- 22143053
TI  - In situ nanochemical imaging of label-free drugs: a case study of antimalarials
      in Plasmodium falciparum-infected erythrocytes.
AB  - We report here for the first time the in vitro localization of unlabeled
      antimalarial drugs with high spatial resolution. This strategy further enhances
      our understanding of the action mechanisms of antimalarial drugs. Our approach
      may be applied to a wide range of domains where quantitative chemical imaging of
      drugs at the sub-cellular level appears critical.

PMID- 22143054
TI  - Carcinogenic 3-nitrobenzanthrone but not 2-nitrobenzanthrone is metabolised to an
      unusual mercapturic acid in rats.
AB  - 3-Nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspect human
      carcinogen found in diesel exhaust. Its isomer 2-nitrobenzanthrone (2-NBA) has
      also been found in ambient air. These isomers differ in mutagenicity in
      Salmonella by 2-3 orders of magnitude. To identify their urinary metabolites and
      also to assess the assumed differences in their excretion, rats were dosed orally
      with 2mg/kg b.w. of either 2-NBA or 3-NBA. Their urine was collected for two
      consecutive days after dosage. Both LC-ESI-MS and GC-MS confirmed formation of
      the corresponding aminobenzanthrones (ABA). Excretion of these metabolites within
      the first day after dosing with 2- and 3-ABA amounted to 0.32+/-0.06 and 0.83+/
      0.40% of the doses, respectively, while the excretion within the second day was
      by one order of magnitude lower. A novel mercapturic acid metabolite of 3-NBA was
      identified in urine by LC-ESI-MS as N-acetyl-S-(3-aminobenzanthron-2-yl)cysteine
      (3-ABA-MA) by comparison with the authentic standard. Its excretion amounted to
      0.49+/-0.15 and 0.02+/-0.01% of dose within the first and second day after
      dosing, respectively. In contrast, no mercapturic acid was detected in the urine
      of rats dosed with 2-NBA. Observed difference in the mercapturic acid formation
      between 2- and 3-NBA is a new distinctive feature reflecting differences in the
      critical step of their metabolism, i.e., benzanthronylnitrenium ion formation
      that is intrinsically associated with biological activities of these two isomers.
      Moreover, 3-ABA-MA is a promising candidate biomarker of exposure to the
      carcinogenic 3-NBA.

PMID- 22143055
TI  - Mono-2-ethylhexylphthalate (MEHP) induces TNF-alpha release and macrophage
      differentiation through different signalling pathways in RAW264.7 cells.
AB  - Epidemiological studies have associated indoor phthalate exposure with increased
      incidences and severity of asthma in children and adults, and inflammatory
      effects have been suggested as a possible mechanism. Recent studies report that
      phthalates may activate mitogen-activated protein (MAP) kinase p38 and various
      peroxisome proliferator-activated receptor (PPAR) isoforms. Here we confirm and
      extend these findings by investigating possible signalling pathways activated in
      the murine monocyte-macrophage cell line RAW264.7, using mono-2
      ethylhexylphthalate (MEHP) as a model compound. MEHP exposure (0.3-1.0 mM) for 3h
      increased tumour necrosis factor (TNF)-alpha release and changed the cellular
      morphology into elongated spindle-like appearance, resembling more differentiated
      anti-inflammatory macrophages (M2). This was accompanied by increased expression
      of the macrophage differentiation marker CD163. Western analysis showed
      phosphorylation of p38 and Akt after 30 min exposure. Experiments using specific
      inhibitors suggested that MEHP-induced activation of both p38 and the
      phosphoinositide-3 (PI3) kinase/Akt pathway were involved in the release of TNF
      alpha; whereas only PI3kinase seemed to be involved in differentiation. In
      contrast, inhibitors of PPARalpha and gamma reduced differentiation, but did not
      affect TNF-alpha release. In conclusion, MEHP induced cytokine release and
      triggered differentiation of RAW264.7 cells, possibly into M2-like macrophages,
      but different signalling pathways appear to be involved in these responses.

PMID- 22143056
TI  - N-Terminal pro-brain natriuretic peptide as a predictor of heart failure with
      preserved ejection fraction in hemodialysis patients without fluid overload.
AB  - BACKGROUND/AIMS: The diagnostic value of N-terminal pro-brain natriuretic peptide
      (NT-pro BNP) for heart failure with preserved ejection fraction (EF; HF-PEF) was
      evaluated in hemodialysis (HD) patients. METHOD: In total, 83 patients were
      analyzed. Left-ventricular (LV) function was assessed using trans-thoracic
      Doppler echocardiography, and indices of hydration status were assessed using
      bioelectrical impedance analysis. Plasma NT-pro BNP levels were measured
      simultaneously. RESULTS: A moderate negative correlation was found between NT-pro
      BNP and LVEF. Subsequently, 77 HD patients who maintained their LVEF (LVEF >50%)
      were analyzed. Patients with a clinical suspicion of LV diastolic dysfunction
      (LVDD; E/A <=0.75) showed higher NT-pro BNP levels (p = 0.021), but no
      significant differences in hydration status were observed between the two groups.
      CONCLUSIONS: The NT-pro BNP level may be a very helpful biomarker in screening
      for LVDD and HF-PEF and determining the need for echocardiography or a
      sophisticated cardiac study, even in HD patients.

PMID- 22143057
TI  - Chronic lymphocytic leukemia: new choices for an old condition.

PMID- 22143058
TI  - Clinical aspects of monoclonal B-cell lymphocytosis.
AB  - BACKGROUND: Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic precursor
      condition for chronic lymphocytic leukemia (CLL). It is defined by the presence
      of small clones of aberrant B cells in the peripheral blood, with a total B-cell
      count below the threshold for diagnosis of CLL (<5.0x10(9) cells/L). METHODS: The
      authors review current literature on the prevalence of MBL, and the clinical
      course of this CLL precursor condition, and recommended management for
      individuals with MBL. RESULTS: MBL occurs in approximately 4% to 5% of healthy
      adults. While most cases of CLL are preceded by MBL, progression to leukemia
      requiring CLL treatment occurs in only 1% to 2% of individuals with MBL per year.
      The absolute B-cell count is most strongly associated with progression, and
      patients with low-count MBL identified in population screening studies rarely
      develop CLL. Studies are ongoing to better define the relationship between MBL
      and CLL and to identify prognostic indicators that predict which patients will
      progress to CLL. Given their elevated risk of developing malignancy, individuals
      with clinical MBL should be monitored at least annually for progressive
      lymphocytosis and signs or symptoms of CLL. CONCLUSIONS: Many of the
      epidemiologic and genetic factors associated with MBL development and its
      progression to CLL have not yet been identified. However, ongoing studies by many
      research groups are aimed at answering these questions to facilitate management
      of individuals with this premalignant condition. In addition, active
      investigation of MBL will likely yield new insights into the biology of CLL,
      potentially identifying new therapeutic targets for this incurable disease.

PMID- 22143059
TI  - Clinical and laboratory prognostic indicators in chronic lymphocytic leukemia.
AB  - BACKGROUND: The clinical course of patients with chronic lymphocytic leukemia
      (CLL) is heterogeneous, with some patients experiencing rapid disease progression
      and others living for decades without requiring treatment. The Rai and Binet
      clinical staging systems are used to define disease extent and predict survival.
      The pathology laboratory also provides important prognostic information. METHODS:
      A review of the literature was performed on the subject of staging in CLL from
      clinical and pathologic standpoints. This article also reviews currently
      available diagnostic approaches related to disease prognosis and to timing of
      treatment and follow-up in patients with CLL. RESULTS: Novel biological and
      cytogenetic features such as immunoglobulin heavy-chain variable gene segment
      [IgVH], genomic aberrations including del(17p13), del(11q23), del(13q14), and
      trisomy 12, serum markers (thymidine kinase and beta-2 microglobulin), and
      cellular markers (CD38 and ZAP70) have become increasingly important in
      predicting prognosis at the time of diagnosis. CONCLUSIONS: Current prognostic
      factors directly or indirectly influence the management of patients with CLL and
      help to predict treatment-free and overall survival.

PMID- 22143060
TI  - Front-line therapy for chronic lymphocytic leukemia.
AB  - BACKGROUND: Historically, alkylator-based therapy has been used to treat patients
      with chronic lymphocytic leukemia (CLL). More effective therapies, such as the
      use of monoclonal antibodies in combination with chemotherapy, have been shown to
      prolong both progression-free survival and overall survival. Improvements in the
      identification of prognostic markers for CLL, as well as novel combinations for
      chemoimmunotherapy regimens, have improved the outcome for patients with CLL.
      METHODS: We examine the diagnosis of CLL, the role of prognostic factors in
      determining treatment goals, and current data on front-line management of CLL.
      RESULTS: The benefits of single-agent and combination therapies are associated
      with prolonged progression-free and overall survival. While more aggressive
      management may therefore be warranted, each patient's comorbidities and
      performance status must be weighed against the benefits, availability, cost,
      treatment goals, and incidence of adverse effects associated with each therapy.
      CONCLUSIONS: New single agents and novel treatment combinations have shown
      promising results in phase I/II studies. The ultimate therapeutic goals of
      prolonged survival and improved quality of life will be validated only by ongoing
      clinical and laboratory research and by continuous enrollment of patients in
      clinical trials.

PMID- 22143061
TI  - Treatment of relapsed or refractory chronic lymphocytic leukemia.
AB  - BACKGROUND: Recent advances in the treatment of chronic lymphocytic leukemia
      (CLL) have moved beyond the traditional use of alkylating agents and purine
      analogs into regimens combining these two chemotherapy classes with monoclonal
      antibodies. METHODS: This article reviews treatments options for patients with
      relapsed or refractory CLL. RESULTS: Several studies have investigated novel
      agents in treating patients with 17p deletion, TP53 mutation, and fludarabine
      refractory CLL, as well as patients with suboptimal response to intense
      treatment. These investigational agents include rituximab, alemtuzumab,
      ofatumumab, bendamustine, high-dose methylprednisolone, lenalidomide,
      lumiliximab, cyclin-dependent kinase inhibitors, small modular
      immunopharmaceuticals, Bcl-2 inhibitors, and histone deacetylase inhibitors.
      While these newer drugs and combination therapies have shown promise as treatment
      options for CLL, additional studies are needed to determine the
      immunosuppression, toxicities, and infections associated with their use.
      CONCLUSIONS: Despite improvement in initial overall response rates, most patients
      relapse and require further treatment. CLL remains incurable with standard
      therapies due to development of disease refractoriness. As such, novel approaches
      such as those noted above warrant continued research to improve outcomes for
      patients with CLL.

PMID- 22143062
TI  - Immunomodulatory drugs and active immunotherapy for chronic lymphocytic leukemia.
AB  - BACKGROUND: The last decade witnessed the emergence of several therapeutic
      options for patients with chronic lymphocytic leukemia (CLL) for first-line and
      relapsed settings. The vast majority of patients with relapsed or refractory CLL
      carry poor prognostic features, which are strong predictors of shorter overall
      survival and resistance to first-line treatment, particularly fludarabine-based
      regimens. METHODS: This article highlights the current role of immunomodulatory
      drugs (IMiDs) and active immunotherapy as treatment options for this select
      group. The rationale of using IMiDs is discussed from the perspective of
      lenalidomide as a novel active agent. Relevant clinical trials using IMiDs alone
      or in combinations are discussed. New immunotherapeutic experimental approaches
      are also described. RESULTS: As a single agent, lenalidomide offers an overall
      response rate of 32% to 47% in patients with relapsed/refractory disease. Recent
      studies have shown promising activity as a single agent in treatment-naive
      patients. The combination of lenalidomide with immunotherapy (rituximab and
      ofatumumab) has also shown clinical responses. Encouraging preclinical and early
      clinical data have been observed with different immunotherapeutic approaches.
      CONCLUSIONS: The use of IMiDs alone or in combination with immunotherapy
      represents a treatment option for relapsed/refractory or treatment-naive
      patients. Mature data and further studies are needed to validate overall and
      progression-free survival. The toxicity profile of lenalidomide might limit its
      use and delay further studies. Immunotherapy offers another potential
      alternative, but further understanding of the immunogenicity of CLL cells and the
      mechanisms of tumor fl are reaction is needed to improve the outcomes in this
      field.

PMID- 22143063
TI  - Hematopoietic stem cell allografting for chronic lymphocytic leukemia: a focus on
      reduced-intensity conditioning regimens.
AB  - BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) remains the
      only known treatment modality that currently offers a potential cure to patients
      with chronic lymphocytic leukemia (CLL). A better understanding of the role of
      adoptive immunotherapy and its consequent bona fide graft-vs-leukemia (GVL)
      effect has resulted in a reduction of the ablative intensity and toxicity of
      preparative allo-HCT regimens. METHODS: The authors review the published data of
      reduced-intensity conditioning (RIC) allo-HCT in patients with CLL. RESULTS: RIC
      allo-HCT has reduced the transplant associated morbidity and mortality of the
      procedure and has consequently broadened applicability of allo-HCT to patients
      with CLL who are generally of more advanced age (> 60 years) and who often have
      associated comorbidities. CONCLUSIONS: Published literature supports the use of
      RIC allo-HCT for these patients once a suitable donor is identified, provided
      they fulfill acceptable consensus criteria for hematopoietic stem cell
      allografting. Several studies have shown that T-cell-replete RIC allo-HCT is also
      capable of overcoming the adverse effect of poor prognostic factors in CLL such
      as del(17p), unmutated IgVH, or ZAP-70 expression. Continued clinical trials to
      identify the optimal regimen for RIC allo-HCT for patients with CLL are
      warranted.

PMID- 22143065
TI  - Energies and pressures in viruses: contribution of nonspecific electrostatic
      interactions.
AB  - We summarize some aspects of electrostatic interactions in the context of
      viruses. A simplified but, within well defined limitations, reliable approach is
      used to derive expressions for electrostatic energies and the corresponding
      osmotic pressures in single-stranded RNA viruses and double-stranded DNA
      bacteriophages. The two types of viruses differ crucially in the spatial
      distribution of their genome charge which leads to essential differences in their
      free energies, depending on the capsid size and total charge in a quite different
      fashion. Differences in the free energies are trailed by the corresponding
      characteristics and variations in the osmotic pressure between the inside of the
      virus and the external bathing solution.

PMID- 22143064
TI  - Cerebral blood flow during reperfusion predicts later brain damage in a mouse and
      a rat model of neonatal hypoxic-ischemic encephalopathy.
AB  - Children with severe neonatal hypoxic-ischemic encephalopathy (HIE) die or
      develop life-long neurological impairments such as cerebral palsy and mental
      retardation. Decreased regional cerebral blood flow (CBF) is believed to be the
      predominant factor that determines the level of tissue injury in the immature
      brain. However, the spatio-temporal profiles of CBF after neonatal HIE are not
      well understood. CB17 mouse and Wistar rat pups were exposed to a unilateral
      hypoxic-ischemic (HI) insult at eight or seven days of age. Laser speckle imaging
      sequentially measured the cortical surface CBF before the hypoxic exposure and
      until 24h after the hypoxic exposure. Seven days after the HI insult, brain
      damage was morphologically assessed by measuring the hemispheric volumes and by
      semi-quantitative scoring for neuropathologic injury. The mean CBF on the
      ipsilateral hemisphere in mice decreased after carotid artery ligation. After the
      end of hypoxic insult (i.e., the reperfusion phase), the mean CBF level gradually
      rose and nearly attained its pre-surgery level by 9h of reperfusion. It then
      decreased. The degree of reduced CBF during reperfusion was well correlated with
      the degree of later morphological brain damage. The correlation was the strongest
      when the CBF was measured in the ischemic core region at 24h of reperfusion in
      mice (R2=0.89). A similar trend in results was found in rats. These results
      suggest that the CBF level during reperfusion may be a useful predictive factor
      for later brain damage in immature mice. This may enable optimizing brain damage
      for detail analyses.

PMID- 22143066
TI  - Migration dynamics of breast cancer cells in a tunable 3D interstitial flow
      chamber.
AB  - The migration of cells such as leukocytes, tumor cells, and fibroblasts through
      3D matrices is critical for regulating homeostasis and immunity and for driving
      pathogenesis. Interstitial flow through the extracellular matrix, which can
      substantially increase during inflammation and in the tumor microenvironment, can
      influence cell migration in multiple ways. Leukocytes and tumor cells are
      heterogeneous in their migration responses to flow, yet most 3D migration studies
      use endpoint measurements representing average characteristics. Here we present a
      robust new microfluidic device for 3D culture with live imaging under well
      controlled flow conditions, along with a comparison of analytical methods for
      describing the migration behavior of heterogeneous cell populations. We then use
      the model to provide new insight on how interstitial flow affects MDA-MB-231
      breast cancer cell invasion, phenomena that are not seen from averaged or
      endpoint measurements. Specifically, we find that interstitial flow increases the
      percentage of cells that become migratory, and increases migrational speed in
      about 20% of the cells. It also increases the migrational persistence of a
      subpopulation (5-10% of cells) in the positive or negative flow direction. Cells
      that migrated upstream moved faster but with less directedness, whereas cells
      that migrated in the direction of flow moved at slower speeds but with higher
      directedness. These findings demonstrate how fluid flow in the tumor
      microenvironment can enhance tumor cell invasion by directing a subpopulation of
      tumor cells in the flow direction; i.e., towards the draining lymphatic vessels,
      a major route of metastasis.

PMID- 22143067
TI  - Surgical and chemotherapeutic options for urachal carcinoma: report of ten cases
      and literature review.
AB  - OBJECTIVE: Several studies have associated urachal carcinoma with a poor
      prognosis, because the disease tends to be detected later as the patient is
      asymptomatic, there are few therapeutic options, and it has a high local
      recurrence rate. We review our experience with urachal carcinoma and discuss the
      role of surgical management and chemotherapeutic options. PATIENTS AND METHODS:
      We reviewed the records of 10 cases with urachal carcinoma evaluated at Keio
      University Hospital from 1998 to 2009, and examine the surgical and
      chemotherapeutic options in the management of urachal carcinoma. RESULTS: Median
      age was 55.0 years. Applying the TNM staging system, 1 case was in stage I, 4
      cases in stage II, 4 cases in stage III, and 1 case was in stage IV. Nine cases
      were managed initially with surgery; 5 by partial cystectomy and 4 by total
      cystectomy. The median follow-up period was 3.5 years and the survival rate at 2
      years was 87.5%. Six of the resected cases remain disease-free. Salvage
      chemotherapy was performed in 3 cases, and adjuvant chemotherapy was performed in
      2 cases. CONCLUSIONS: We had 10 cases with urachal carcinoma. While there is
      still no standard chemotherapy combination, CPT-11 plus TS-1 produced stable
      disease in 1 case.

PMID- 22143068
TI  - Mutations to create thermostable reverse transcriptase with bacterial family A
      DNA polymerase from Thermotoga petrophila K4.
AB  - Family A DNA polymerase (K4PolI) from Thermotoga petrophila K4 was obtained as a
      recombinant form, and the enzyme characteristics were analyzed. K4PolI showed
      thermostable DNA-dependent DNA polymerase activity with 3'-5' exonuclease
      activity but no detectable RNA-dependent DNA polymerase activity. Its tertiary
      structure was speculated by in silico modeling to understand the binding
      situation between K4PolI and template DNA. Nine amino acids in the 3'-5'
      exonuclease domain are predicted to be involved in DNA/RNA distinction by steric
      interference with the 2' hydroxy group of ribose. To allow K4PolI to accept RNA
      as the template, mutants were constructed focusing on the amino acids located
      around the 2' hydroxyl group of the bound ribose. The mutants in which Thr326,
      Leu329, Gln384, Phe388, Met408, or Tyr438 was replaced with Ala (designated as
      T326A, L329A, Q384A, F388A, M408A, or Y438A, respectively) showed RNA-dependent
      DNA polymerase activity. All the mutants showed reduced 3'-5' exonuclease
      activity, suggesting that gain of reverse transcriptase activity is correlated
      with loss of 3'-5' exonuclease activity. In particular, the mutants enabled
      direct DNA amplification in a single tube format from structured RNA that was not
      efficiently amplified by retroviral reverse transcriptase.

PMID- 22143069
TI  - Simplified preparation of crude and functional coagulogen by thermal inactivation
      of serine proteases in Limulus amebocyte lysate and its application for rapid
      endotoxin determination.
AB  - The effects of thermal treatment on Limulus amebocyte lysate (LAL) reagent were
      studied. Thermal resistances of enzymes and coagulogen in LAL reagent were
      evaluated by aggregometry and SDS-PAGE. Although enzyme activities of LAL reagent
      were completely lost after heating at temperatures above 60  degrees C for 10
      min, gelating activities of coagulogen were retained even over 80  degrees C.
      Phenylmethanesulfonyl fluoride (PMSF; 1 mmol/mL), a strong non-specific serine
      protease inhibitor, did not completely inactivate serine-protease activities of
      LAL. As a result, complete hydrolysis of coagulogen to coagulin was unexpectedly
      obtained. Solvent treatment of LAL was similar in effect to thermal treatment of
      LAL, but there were 2 problems: complete removal of solvent from samples and
      increased solution turbidity during preparation. To study the application of
      thermal-treated LAL, we conjugated it with titania particles. LAL-conjugated
      titania particles were obtained as small aggregates between titania nanoparticles
      and thermal-treated LAL (LAL-conjugated microbeads; LCM). When the mixture of
      LCMs and fresh LAL reagent was reacted with endotoxin an acute aggregation of
      LCMs was induced prior to the aggregate formation of LAL as monitored by stirring
      turbidimetry. This method, endotoxin microbeads aggregometry (EMA) may provide a
      rapid and sensitive method for endotoxin determination.

PMID- 22143070
TI  - Mutations to the active site of 3-ketoacyl-ACP synthase III (FabH) increase
      polyhydroxyalkanoate biosynthesis in transgenic Escherichia coli.
AB  - Polyhydroxyalkanoate (PHA) production has been enhanced with engineered 3
      ketoacyl-ACP synthase III (FabH) enzymes that accept diverse fatty acyl-ACP
      substrates and convert them to fatty acyl-CoA substrates for polymerization by
      PHA synthase enzymes resulting in the production of diverse polymers. Two
      mutations in the monomer supplying enzyme FabH, His244Ala and the Asn274Ala, were
      investigated to assess the impact of these mutations on PHA monomer production.
      PHA production increased more than six-fold with the mutation His244Ala in the
      FabH enzyme. Engineering of the FabH enzyme for improved PHA monomer supply led
      to a more productive system for PHA copolymer production.

PMID- 22143071
TI  - Stam2 expression pattern during embryo development.
AB  - STAM2 is a tyrosine-phosphorylated protein suggested to be involved in cargo
      selection during endocytic pathway, regulation of exocytosis and intracellular
      signaling. Gene trap method was used to create via insertional mutagenesis a
      mutant mouse line with integration of promoterless betageo (lacZ-neomycin
      phosphotransferase fusion) gene in the second intron of Stam2 gene, enabling
      analysis of its in vivo expression and function. The inserted beta-galactosidase
      (lacZ) reporter gene was used to reveal Stam2 expression during development.
      Stam2 in situ RNA hybridization and immunostaining confirmed the observed beta
      galactosidase activity reflecting high Stam2 expression. The homozygous mutant
      mice showed no overt phenotypic alterations. Stam2 expression was detected after
      E9.5 in the gut, notochord, neural tube and heart. In the nervous system it was
      located in the floor, roof and basal plates of the developing neural tube, and in
      the developing cortex, hippocampus and olfactory bulbs. Toward the end of
      gestation, Stam2 expression appeared in the testis and ovary, lungs, nasal cavity
      epithelium, kidneys, urogenital sinus, intestine, pancreas, pituitary and adrenal
      glands, muscles, brown adipose tissue, skin and epithelium of the tongue and oral
      cavity.

PMID- 22143072
TI  - Safety and efficacy of electroconvulsive therapy for the treatment of agitation
      and aggression in patients with dementia.
AB  - OBJECTIVES: Noncognitive behavioral disturbances including agitation and
      aggression frequently accompany the cognitive symptoms of dementia accounting for
      much of dementia's morbidity, yet treatment options are currently limited. The
      authors examine the safety and efficacy of Electroconvulsive Therapy (ECT) for
      agitation and aggression in dementia patients. DESIGN: Retrospective systematic
      chart review. SETTING: McLean Hospital's geriatric neuropsychiatry unit.
      PARTICIPANTS: Sixteen patients with a diagnosis of dementia treated with ECT for
      agitation/aggression during 2004-2007. MEASUREMENTS: Clinical charts were rated
      on the Pittsburgh Agitation Scale as the primary outcome, the Clinical Global
      Impression scale and the Global Assessment of Functioning pre- and post-ECT.
      RESULTS: 16 patients of mean age 66.6 +/- 8.3 years were studied. Their average
      overall and pre-ECT lengths of stay were 59.7 +/- 39.7 days and 23 +/- 15.7 days,
      respectively. Patients received a mean of 9 ECT treatments, mostly bilateral.
      Patients showed significant reductions in their total Pittsburgh Agitation Scale
      scores from baseline after ECT (from 11.0 +/- 5.0 to 3.9 +/- 4.3 [F = 30.33, df =
      1, 15, p < 0.001]). Clinical Global Impression scale decreased significantly
      (from 6.0 +/- 0.6 pre-ECT to 2.1 +/- 1.6 post-ECT [F = 112.97, df = 1, 15, p <
      0.001]). Global Assessment of Functioning change was not significant (from 23.0
      +/- 4.9 to 26.9 +/- 6.9 [F = 5.73, df = 1, 13, p = 0.32]). Only one patient, in
      whom ECT was discontinued following 11 bilateral treatments, showed no
      improvement. Eight patients showed transient postictal confusion, which typically
      resolved within 48 hours. Two patients showed more severe postictal confusion
      that required modification of treatment. CONCLUSIONS: These results suggest that
      ECT is an effective and safe treatment for agitation and aggression in dementia.
      Further prospective studies are warranted.

PMID- 22143073
TI  - Sensing HIV related protein using epitope imprinted hydrophilic polymer coated
      quartz crystal microbalance.
AB  - We have developed a biomimetic sensor for the detection of human immunodeficiency
      virus type 1 (HIV-1) related protein (glycoprotein 41, gp41) based on epitope
      imprinting technique. gp41 is the transmembrane protein of HIV-1 and plays an
      important role in membrane fusion between viruses and infected cells. It is an
      important index for determining the extent of HIV-1 disease progression and the
      efficacy of therapeutic intervention. In this work, dopamine was used as the
      functional monomer and polymerized on the surface of quartz crystal microbalance
      (QCM) chip in the presence of template, a synthetic peptide with 35 amino acid
      residues, analogous to residues 579-613 of the gp41. This process resulted in
      grafting a hydrophilic molecularly imprinted polymer (MIP) film on the QCM chip.
      QCM measurement showed that the resulting MIP film not only had a great affinity
      towards the template peptide, but also could bind the corresponding gp41 protein
      specifically. The dissociation constant (K(d)) of MIP for the template peptide
      was calculated to be 3.17 nM through Scatchard analysis, which was similar to
      those of monoclonal antibodies. Direct detection of the gp41 was achieved
      quantitatively using the resulting MIP-based biomimetic sensor. The detection
      limit of gp41 was 2 ng/mL, which was comparable to the reported ELISA method. In
      addition, the practical analytical performance of the sensor was examined by
      evaluating the detection of gp41 in human urine samples with satisfactory
      results.

PMID- 22143074
TI  - Immunosuppressive therapies in the management of acquired immune-mediated marrow
      failures.
AB  - PURPOSE OF REVIEW: Immunosuppression is a key treatment strategy for patients
      suffering from aplastic anemia or related immune-mediated bone marrow failure
      syndromes. Several attempts have been performed to improve the standard
      immunosuppression regimen of horse antithymocyte globulin (h-ATG) and
      cyclosporine A (CyA). RECENT FINDINGS: The addition of a third immunosuppression
      agent to h-ATG + CyA did not result in any improvement. Antilymphocyte agents
      other than h-ATG have been investigated. A rabbit-ATG preparation, which was
      known to be more immunosuppressive than h-ATG, resulted in markedly inferior
      outcome in a large randomized study from the National Institutes of Health. These
      data seem to be confirmed in additional experiences with rabbit-ATG from other
      groups. Cyclophosphamide and alemtuzumab have been proven to be biologically
      active in small studies, but available data suggest inferior outcomes when
      compared with h-ATG. All these alternative agents result in a more pronounced
      lymphocyte depletion, suggesting that the actual mechanisms of action of
      immunosuppressive therapy in aplastic anemia are not fully understood. SUMMARY:
      Immunosuppression by h-ATG and CyA remains the standard of care for aplastic
      anemia patients lacking a low-risk transplant procedure, resulting in a 60-70%
      response rate. Rabbit-ATG, cyclophosphamide and alemtuzumab demonstrated a
      biological activity, but resulted in inferior outcome as compared with h-ATG;
      thus, they are not recommended as front-line therapy of aplastic anemia.

PMID- 22143075
TI  - Agranulocytosis and other consequences due to use of illicit cocaine contaminated
      with levamisole.
AB  - PURPOSE OF REVIEW: Most of the illicit cocaine consumed in the United States and
      elsewhere is contaminated with levamisole, a veterinary medication.
      Agranulocytosis caused by levamisole exposure through cocaine abuse was first
      described in 2009. Since then, levamisole has also been shown and is known to
      cause vascular and neurologic complications. In this review, we provide an
      overview of the medical consequences of exposure to levamisole from adulterated
      cocaine. RECENT FINDINGS: Within the past year, several new case series have
      deepened our understanding of the levamisole-agranulocytosis vasculopathy
      syndrome. The common nature of this exposure has been delineated, cocaine
      contaminated with levamisole. Significant controversy surrounds the role of
      granulocyte colony stimulating factor (GCSF) in levamisole-associated
      agranulocytosis. SUMMARY: More than three fourths of cocaine users in the United
      States are exposed to levamisole; a significant minority of these individuals
      will develop autoimmune-mediated neutropenia, cutaneous vascular complications,
      and/or leukoencephalopathy. Levamisole exposure should be considered in the
      differential diagnosis of patients who present with these conditions in the
      setting of cocaine abuse. Neutropenia appears to resolve rapidly with cessation
      of exposure, so that GCSF therapy and a work-up for other causes may not be
      needed in all patients.

PMID- 22143076
TI  - Twenty years of the colony-stimulating factors.

PMID- 22143077
TI  - Progress in adsorption-based CO2 capture by metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) have recently attracted intense research interest
      because of their permanent porous structures, large surface areas, and potential
      applications as novel adsorbents. The recent progress in adsorption-based CO(2)
      capture by MOFs is reviewed and summarized in this critical review. CO(2)
      adsorption in MOFs has been divided into two sections, adsorption at high
      pressures and selective adsorption at approximate atmospheric pressures. Keys to
      CO(2) adsorption in MOFs at high pressures and low pressures are summarized to be
      pore volumes of MOFs, and heats of adsorption, respectively. Many MOFs have high
      CO(2) selectivities over N(2) and CH(4). Water effects on CO(2) adsorption in
      MOFs are presented and compared with benchmark zeolites. In addition, strategies
      appeared in the literature to enhance CO(2) adsorption capacities and/or
      selectivities in MOFs have been summarized into three main categories, catenation
      and interpenetration, chemical bonding enhancement, and electrostatic force
      involvement. Besides the advantages, two main challenges of using MOFs in CO(2)
      capture, the cost of synthesis and the stability toward water vapor, have been
      analyzed and possible solutions and path forward have been proposed to address
      the two challenges as well (150 references).

PMID- 22143078
TI  - Acute coronary syndromes: ACS in developing countries--insights from the ACCESS
      registry.

PMID- 22143080
TI  - Atrial fibrillation: First head-to-head comparison of catheter and surgical
      ablation for drug-refractory AF.

PMID- 22143081
TI  - Stem cells: Do fetal cells repair maternal hearts?

PMID- 22143079
TI  - Reverse remodeling in heart failure--mechanisms and therapeutic opportunities.
AB  - Heart failure (HF) involves changes in cardiac structure, myocardial composition,
      myocyte deformation, and multiple biochemical and molecular alterations that
      impact heart function and reserve capacity. Collectively, these changes have been
      referred to as 'cardiac remodeling'. Understanding the components of this process
      with the goal of stopping or reversing its progression has become a major
      objective. This concept is often termed 'reverse remodeling', and is successfully
      achieved by inhibitors of the renin-angiotensin-aldosterone system, beta
      blockers, and device therapies such as cardiac resynchronization or ventricular
      assist devices. Not every method of reverse remodeling has long-lasting clinical
      efficacy. However, thus far, every successful clinical treatment with long-term
      benefits on the morbidity and mortality of patients with HF reverses remodeling.
      Reverse remodeling is defined by lower chamber volumes (particularly end-systolic
      volume) and is often accompanied by improved beta-adrenergic and heart-rate
      responsiveness. At the cellular level, reverse remodeling impacts on myocyte
      size, function, excitation-contraction coupling, bioenergetics, and a host of
      molecular pathways that regulate contraction, cell survival, mitochondrial
      function, oxidative stress, and other features. Here, we review the current
      evidence for reverse remodeling by existing therapies, and discuss novel
      approaches that are rapidly moving from preclinical to clinical trials.

PMID- 22143082
TI  - Atrial fibrillation: Colchicine lowers postoperative AF risk.

PMID- 22143083
TI  - Comparable analysis of outcomes for allogeneic peripheral blood stem cell
      transplantation from matched related and matched unrelated donors in acute
      myeloid leukemia.
AB  - This study compared the results of allogeneic peripheral blood stem cell
      transplantation (PBSCT) from unrelated and related donors in 142 consecutive
      patients with acute myeloid leukemia (AML). The cumulative incidence of acute
      graft-versus-host disease (GVHD) was 37.6% in the related PBSCT group and 53.7%
      in the unrelated PBSCT group. The cumulative incidence of extensive chronic GVHD
      was also higher in the unrelated PBSCT group (19.5%) than in the related PBSCT
      group (8.9%). The overall survival rate at 4 years was 62.4 +/- 5.4 and 53.8 +/-
      1.2% (p = 0.535) in the related and unrelated PBSCT group, respectively. In a
      multivariate analysis, unrelated PBSCT was identified as a risk factor for the
      development of extensive chronic GVHD (hazard ratio = 3.019, p = 0.027).
      Unfavorable cytogenetics and the disease status at the time of transplantation
      were found to be related to overall survival. In the case of high-risk AML, the
      survival rate and relapse incidence were significantly better in the matched
      unrelated PBSCT group (p = 0.047 and 0.039, respectively). In conclusion, the
      allogeneic PBSCT outcomes for AML were comparable in the matched related and
      matched unrelated groups. Nonetheless, for high-risk AML patients, matched
      unrelated PBSCT was found to be preferable to matched related PBSCT.

PMID- 22143084
TI  - A non-volatile memory device consisting of graphene oxide covalently
      functionalized with ionic liquid.
AB  - We introduce non-volatile resistive crossbar memory based on ionic liquid
      covalently functionalized on a partially reduced graphene oxide (PrGO). The write
      read-erase-read (WRER) cycles were very stable after several hundred cycles and
      the retention time of both the ON and OFF states was stable for over 1000 s,
      indicating that the device we developed can function as a non-volatile memory
      device.

PMID- 22143086
TI  - Drug solubilization and in vitro toxicity evaluation of lipoamino acid
      surfactants.
AB  - To improve solubilization of a water insoluble anticancer drug, novel surfactants
      were synthesized. All surfactants derived from lysine, with a so-called nitrilo
      triacetic acid (NTA) polar head, and differed from the length and saturation
      degree of their hydrophobic moieties: C19:0-NTA, C20:4-NTA, C25:0-NTA and C25:4
      NTA. Self-assembling properties and critical micellar concentration (CMC) values
      were determined using pyrene fluorescence and cytotoxicity using MTT and LDH
      assays on endothelial cells. Surfactant haemolytic activity and drug
      solubilization capacity were also evaluated. All surfactants self-assemble with
      low CMC values from 0.012 to 0.430 mg/mL. Cytotoxicity assays showed that C20:4
      NTA and C25:0-NTA were less cytotoxic than polysorbate 80. Unsaturations and
      alkane chain length have a marked influence on toxicity. Saturated surfactants
      had a similar haemolytic activity, explained by their low CMC values and the
      linear configuration of their hydrophobic tail. C20:4-NTA and C25:4-NTA were less
      haemolytic than polysorbate 80. Furthermore, C19:0-NTA, C25:0-NTA and C25:4-NTA
      increased drug solubility from <0.15 MUg/mL up to 7 mg/mL, with 46% (w/w) drug
      loading, due to their linear and flexible hydrophobic chain configuration, as
      evidenced by molecular modelling. Although these solubilizers are promising, a
      compromise between drug solubilization and toxicity remains to be found.

PMID- 22143087
TI  - Recent progress in non-viral nucleic acids delivery.

PMID- 22143089
TI  - Acanthamoeba is an evolutionary ancestor of macrophages: a myth or reality?
AB  - Given the remarkable similarities in cellular structure (morphological and ultra
      structural features), molecular motility, biochemical physiology, ability to
      capture prey by phagocytosis and interactions with microbial pathogens, here we
      pose the question whether Acanthamoeba and macrophages are evolutionary related.
      This is discussed in the light of evolution and functional aspects such as the
      astonishing resemblance of many bacteria to infect and multiply inside human
      macrophages and amoebae in analogous ways. Further debate and studies will
      determine if Acanthamoeba is an evolutionary ancestor of macrophages. Is this a
      myth or reality?

PMID- 22143088
TI  - Perspectives on the potential of entomopathogenic fungi in biological control of
      ticks.
AB  - Ticks are serious health threats for humans, and both domestic and wild animals.
      Ticks are controlled mostly by application of chemical products; but these
      acaricides have several negative side effects, including toxicity to animals,
      environmental contamination, and induction of chemical resistance in some tick
      populations. Entomopathogenic fungi infect arthropods in nature and can occur at
      enzootic or epizootic levels in their host populations. Laboratory studies
      clearly demonstrate that these fungi can cause high mortality in all
      developmental stages of several tick species, and also reduce oviposition of
      infected engorged females. Tick mortality following application of fungi in the
      field, however, often is less than that suggested by laboratory tests. This is
      due to many negative biotic and climatic factors. To increase efficacy of fungal
      agents for biological control of ticks under natural conditions, several points
      need consideration: (1) select effective isolates (viz., high virulence; and
      tolerance to high temperature, ultraviolet radiation and desiccation); (2)
      understand the main factors that affect virulence of fungal isolates to their
      target arthropods including the role of toxic metabolites of the fungal isolates;
      and (3) define with more precision the immune response of ticks to infection by
      entomopathogenic fungi. The current study reviews recent literature on biological
      control of ticks, and comments on the relevance of these results to advancing the
      development of fungal biocontrol agents, including improving formulation of
      fungal spores for use in tick control, and using entomopathogenic fungi in
      integrated pest (tick) management programs.

PMID- 22143090
TI  - In vitro antileishmanial and antitrypanosomal activities of flavanones from
      Baccharis retusa DC. (Asteraceae).
AB  - Leishmaniasis and Chagas' are parasitic protozoan diseases that affect the
      poorest population in the world, causing a high mortality and morbidity. As a
      result of highly toxic and long-term treatments, novel, safe and more efficacious
      drugs are essential. In this work, the CH(2)Cl(2) phase from MeOH extract from
      the leaves of Baccharis retusa DC. (Asteraceae) was fractioned to afford two
      flavonoids: naringenin (1) and sakuranetin (2). These compounds were in vitro
      tested against Leishmania spp. promastigotes and amastigotes and Trypanosoma
      cruzi trypomastigotes and amastigotes. Compound 2 presented activity against
      Leishmania (L.) amazonensis, Leishmania (V.) braziliensis, Leishmania (L.) major,
      and Leishmania (L.) chagasi with IC(50) values in the range between 43 and 52
      MUg/mL and against T. cruzi trypomastigotes (IC(50)=20.17 MUg/mL). Despite of the
      chemical similarity, compound 1 did not show antiparasitic activity.
      Additionally, compound 2 was subjected to a methylation procedure to give
      sakuranetin-4'-methyl ether (3), which resulted in an inactive compound against
      both Leishmania spp. and T. cruzi. The obtained results indicated that the
      presence of one hydroxyl group at C-4' associated to one methoxyl group at C-7 is
      important to the antiparasitic activity. Further drug design studies aiming
      derivatives could be a promising tool for the development of new therapeutic
      agents for Leishmaniasis and Chagas' disease.

PMID- 22143091
TI  - Tricuspid valve papillary fibroelastoma: an unusual case of dizzy spells.
AB  - An 81-year-old woman with recurrent episodes of dizzy spells was found to have a
      mass in the right atrium on transthoracic echocardiography. The patient underwent
      successful surgery to excise the mass, which was arising from the anterior
      leaflet of the tricuspid valve. Histology showed a papillary fibroelastoma.
      Although management is still controversial when such tumours are found
      incidentally in asymptomatic patients, surgery may be considered, especially if
      the tumour is large, due to the high risk of embolism.

PMID- 22143092
TI  - A simple technique to prevent limb ischemia during veno-arterial ECMO using the
      femoral artery: the posterior tibial approach.
AB  - Lower extremity ischemia is common when the femoral artery is used for veno
      arterial extracorporeal membrane oxygenation (VA ECMO). We describe a new
      technique to reperfuse the extremity. The ipsilateral posterior tibial artery is
      exposed via a small incision behind the medial malleolus. The vessel is
      cannulated in a retrograde fashion and connected to the arterial limb of the ECMO
      circuit. Thirty-six patients received a posterior tibial reperfusion cannula:
      average flow was 155.8 ml/min and increased over the initial 24 hours. Fifty
      eight percent received the posterior tibial cannula within 6 hours of ECMO
      initiation and none sustained permanent lower extremity injury. Of the remaining
      42%, three required amputation or developed permanent neurologic injury. Overall
      survival was 41%. Cannulation of the posterior tibial artery is a simple
      technique to reperfuse the lower extremity during VA ECMO. The cannula should be
      inserted within 6 hours of ECMO initiation to avoid irreversible ischemic damage.

PMID- 22143093
TI  - Different roles of the posterior inferior frontal gyrus in Chinese character form
      judgment differences between literate and illiterate individuals.
AB  - In the present study, we used event-related functional magnetic resonance imaging
      (fMRI) to explore the different roles of the posterior inferior frontal gyrus
      (pIFG) in Chinese character form judgment between literate and illiterate
      subjects. Using event-related fMRI, 24 healthy right-handed Chinese subjects (12
      literates and 12 illiterates) were asked to perform Chinese character and figure
      form judgment tasks. The blood oxygen level-dependent (BOLD) differences in pIFG
      were examined with general linear modeling (GLM). We found differences in
      reaction times and accuracy between subjects as they performed these tasks. These
      behavioral differences reflect the different cognitive demands of character form
      judgment for literate and illiterate individuals. The results showed differences
      in the BOLD response patterns in the pIFG between the two discrimination tasks
      and the two subject groups. A comparison of the character and figure tasks showed
      that literate and illiterate subjects had similar BOLD responses in the inferior
      frontal gyrus. However, differences in behavioral performance suggest that the
      pIFG plays a different role in Chinese character form judgment for each subject
      group. In literate subjects, the left pIFG mediated access to phonology in
      achieving Chinese character form judgment, whereas the right pIFG participated in
      the processing of the orthography of Chinese characters. In illiterate subjects,
      the bilateral frontal gyrus participated in the visual-spatial processing of
      Chinese characters to achieve form judgment.

PMID- 22143094
TI  - Human bone marrow mesenchymal stem cells protect catecholaminergic and
      serotonergic neuronal perikarya and transporter function from oxidative stress by
      the secretion of glial-derived neurotrophic factor.
AB  - In neurodegenerative disorders, including Parkinson's disease (PD), the potential
      of mesenchymal stem cells (MSCs) to produce neurorestoration via trans
      differentiation has garnered much interest. We believe, however, that the
      paracrine effects of MSCs may have greater utility. MSCs release neurotrophic
      factors, including glial derived neurotrophic factor (GDNF). The benefits
      conferred by MSC GDNF release could potentially apply to all degenerating
      monoaminergic fibre types, throughout the brains of patients with PD, rather than
      solely affording protection to the dopaminergic neurones of the nigro-striatal
      pathway alone. Using an in vitro approach, we have investigated the
      neuroprotective properties of unmodified human MSCs on rat catecholaminergic and
      serotonergic cell cultures exposed to the damaging effects of nitric oxide. We
      have shown that post oxidative and inflammatory stress, soluble factors produced
      by native human MSCs, requiring no direct cell-cell contact or genetic or other
      manipulation, confer protection not only of cultured monoaminergic perikarya, but
      also of monoamine neurotransmitter transporter function. Furthermore, we have
      confirmed that, in part, this MSC mediated neuroprotective effect is due to MSC
      GDNF release and that such protection is diminished when the action of GDNF is
      blocked. Trophic factor release may afford a way by which intravenously infused
      MSCs can offer protection to all of the dopaminergic, noradrenergic and
      serotonergic fibre types degenerating widely throughout the brains of patients
      with PD.

PMID- 22143095
TI  - Stroke in Asia: time for dignity & justice. Abstracts of the 1st Conference of
      the Asia Pacific Stroke Organization (APSO). Cinnamon Grand, Colombo, Sri Lanka.
      September 29-October 1, 2011.

PMID- 22143096
TI  - Adult extracorporeal membrane oxygenation and gastrointestinal bleeding from
      small bowel arteriovenous malformations: a novel treatment using spiral
      enteroscopy.

PMID- 22143097
TI  - Correction of anterior mitral prolapse: the parachute technique.
AB  - OBJECTIVES: To evaluate a new surgical technique for the correction of anterior
      mitral leaflet prolapse. METHODS: From October 2006 to November 2011, 44
      consecutive patients (28 males, mean age 55 +/- 13 years) underwent mitral valve
      repair because of anterior mitral leaflet prolapse. Echocardiography was
      performed to evaluate the distance from the tip of each papillary muscle to the
      annular plane. A specially designed caliper was used to manufacture a parachute
      like device, by looping a 4-0 polytetrafluoroethylene suture between a Dacron
      strip and Teflon felt pledget, according to the preoperative echocardiographic
      measurements. This parachute was then used to resuspend the anterior mitral
      leaflet to the corresponding papillary muscle. Of the 44 patients, 35 (80%)
      required concomitant posterior leaflet repair. Additional procedures were
      required in 16 patients (36%). The preoperative logistic European System for
      Cardiac Operative Risk Evaluation was 4.3 +/- 6.9. RESULTS: The clinical and
      echocardiographic follow-up were complete. The total follow-up was 1031 patient
      months and averaged 23.4 +/- 17.2 months per patient. The overall mortality rate
      was 4.5% (n = 2). Also, 2 patients (4.5%) with recurrent mitral regurgitation
      required mitral valve replacement, 1 on the first postoperative day and 1 after
      13 months. In the latter patient, histologic analysis showed complete
      endothelialization of the Dacron strip. At follow-up, all non-reoperated
      survivors (n = 40) were in New York Heart Association class I, with no
      regurgitation in 40 patients (93%) and grade 2+ mitral regurgitation in 3 (7%).
      CONCLUSIONS: This technique offers a simple and reproducible solution for
      correction of anterior leaflet prolapse. Echocardiography can reliably evaluate
      the length of the chordae. However, the long-term results must be evaluated and
      compared with other surgical strategies.

PMID- 22143098
TI  - Near-infrared spectroscopy for monitoring leg perfusion during minimally invasive
      surgery for patients with congenital heart defects.

PMID- 22143101
TI  - A decade of pediatric mechanical circulatory support before and after cardiac
      transplantation.
AB  - OBJECTIVES: We reviewed the use of pediatric mechanical circulatory support
      before and after transplantation to examinine current results and future
      strategies. METHODS: All patients listed for transplantation from January 2000 to
      December 2010 who required either extracorporeal membrane oxygenation (ECMO) or
      ventricular assist device (VAD) support before ("intention to transplant") or
      after transplantation were included. Indications for mechanical assistance, age,
      weight, duration of support, complications while on support, causes of death, and
      overall actuarial survival were recorded. RESULTS: Thirty-seven patients were
      received VADs; 32 (86.5%) survived to transplantation. Postoperative hemorrhagic
      or thrombotic complications affected all of those under 15 kg. One patient in the
      survivor cohort demonstrated focal neurologic findings. Three (8.1%) had panel
      reactive antibody levels of 10% or more while on device support; all received
      transplants. ECMO as an intention to bridge to transplantation was used in 28
      patients; 7 died, 7 were weaned, and 14 were bridged to transplantation. Nineteen
      patients required ECMO after transplantation; 3 additional patients had
      percutaneous VAD support for late rejection. There was a significant (P = .02)
      difference in survival after listing for transplantation among those supported
      with ECMO, with VAD, and those not supported with a device. No difference in
      posttransplant survival was demonstrated between those patients supported with
      either ECMO or VAD before transplant compared with all others not bridged to
      transplantation. CONCLUSIONS: Both VAD and ECMO support are highly effective
      means of bridging patients to transplantation and supporting patients after
      transplanatation. Ideally, the availability of smaller devices for children will
      have a favorable impact on the morbidity related to anticoagulation in the
      smallest patients.

PMID- 22143100
TI  - Regional alterations in cerebral growth exist preoperatively in infants with
      congenital heart disease.
AB  - OBJECTIVES: Magnetic resonance imaging has been used to define the neurologic
      abnormalities in infants with congenital heart disease (CHD), including
      preoperative injury and delayed brain maturation. The present study used
      qualitative scoring, cerebral biometry, and diffusion imaging to characterize the
      preoperative brain abnormalities in infants with CHD, including the
      identification of regions of greater vulnerability. METHODS: A total of 67
      infants with CHD had preoperative magnetic resonance imaging scans available for
      analysis of brain injury using qualitative scoring and brain development using
      qualitative scoring, metrics, and diffusion imaging. RESULTS: Qualitative
      abnormalities were common, with 42% of infants having preoperative focal white
      matter lesions. Infants with CHD had smaller brain measures in the frontal lobe,
      parietal lobe, cerebellum, and brainstem (P < .001), with the frontal lobe and
      brainstem displaying the greatest alterations (P < .001). A smaller brain size in
      the frontal and parietal lobes correlated with delayed white matter
      microstructure reflected by diffusion imaging. CONCLUSIONS: Infants with CHD
      commonly display brain injury and delayed brain development. Regional alterations
      in brain size are present, with the frontal lobe and brainstem demonstrating the
      greatest alterations. This might reflect a combination of developmental
      vulnerability and regional differences in cerebral circulation.

PMID- 22143102
TI  - AAV6-betaARKct gene delivery mediated by molecular cardiac surgery with
      recirculating delivery (MCARD) in sheep results in robust gene expression and
      increased adrenergic reserve.
AB  - OBJECTIVE: Genetic modulation of heart function is a novel therapeutic strategy.
      We investigated the effect of molecular cardiac surgery with recirculating
      delivery (MCARD)-mediated carboxyl-terminus of the beta-adrenergic receptor
      kinase (betaARKct) gene transfer on cardiac mechanoenergetics and beta
      adrenoreceptor (betaAR) signaling. METHODS: After baseline measurements, sheep
      underwent MCARD-mediated delivery of 10(14) genome copies of self-complimentary
      adeno-associated virus (scAAV6)-betaARKct. Four and 8 weeks after MCARD,
      mechanoenergetic studies using magnetic resonance imaging were performed. Tissues
      were analyzed with real-time quantitative polymerase chain reaction (RT-qPCR) and
      Western blotting. betaAR density, cyclic adenosine monophosphate levels, and
      physiologic parameters were evaluated. RESULTS: There was a significant increase
      in dP/dt(max) at 4 weeks: 1384 +/- 76 versus 1772 +/- 182 mm Hg/s; and the
      increase persisted at 8 weeks in response to isoproterenol (P < .05). Similarly,
      the magnitude of dP/dt(min) increased at both 4 weeks and 8 weeks with
      isoproterenol stimulation (P < .05). At 8 weeks, potential energy was conserved,
      whereas in controls there was a decrease in potential energy (P < .05) in
      response to isoproterenol. RT-qPCR confirmed robustness of betaARKct expression
      throughout the left ventricle and undetectable expression in extracardiac
      tissues. Quantitative Western blot data confirmed higher expression of betaARKct
      in the left ventricle: 0.46 +/- 0.05 versus 0.00 in lung and liver (P < .05).
      Survival was 100% and laboratory parameters of major organ function were within
      normal limits. CONCLUSIONS: MCARD-mediated betaARKct delivery is safe, results in
      robust cardiac-specific gene expression, enhances cardiac contractility and
      lusitropy, increases adrenergic reserve, and improves energy utilization
      efficiency in a preclinical large animal model.

PMID- 22143103
TI  - Functional outcome after different oncological interventions in head and neck
      cancer patients.
AB  - PURPOSE: Patient-reported outcomes following head and neck cancer are of great
      importance given the functional, psychological, and social impacts of the disease
      and its treatment. With an increasing number of publications on HRQOL following
      head and neck cancer and a growing awareness of the potential role of HRQOL in
      practice, it was our aim to investigate head and neck functional mobility that is
      often not taking into account in HRQOL scores. METHODS: In this prospective
      study, three different groups of 32 patients each were included. Any patient who
      had histologically confirmed invasive OSCC in the anterior floor of the mouth was
      eligible. All patients were examined by a standardized test assessing function,
      including the distance of mouth opening, extension, flexion, and rotation of the
      head. RESULTS: A total of 96 patients were included in this study. The mean age
      was 62.79 +/- 8.93 years. Head and neck mobility measured in patients is
      presented and analyzed. Compared to the baseline, a significant reduction of
      mouth opening and head and neck mobility was noted in all groups. CONCLUSIONS:
      Although both treatment options (surgery and surgery with radiotherapy) were
      performed according to the tumor stage of patients, there are significant
      differences in the functional outcome of these patients as observed in this
      study. There is a lack of a measuring instrument that will be the "gold standard"
      in the assessment of head and neck functional mobility. This study will allow the
      reflection of our current practice and may stimulate further well-designed
      prospective studies.

PMID- 22143104
TI  - Cerebrovascular casting of the adult mouse for 3D imaging and morphological
      analysis.
AB  - Vascular imaging is crucial in the clinical diagnosis and management of
      cerebrovascular diseases, such as brain arteriovenous malformations (BAVMs).
      Animal models are necessary for studying the etiopathology and potential
      therapies of cerebrovascular diseases. Imaging the vasculature in large animals
      is relatively easy. However, developing vessel imaging methods of murine brain
      disease models is desirable due to the cost and availability of genetically
      modified mouse lines. Imaging the murine cerebral vascular tree is a challenge.
      In humans and larger animals, the gold standard for assessing the
      angioarchitecture at the macrovascular (conductance) level is x-ray catheter
      contrast-based angiography, a method not suited for small rodents. In this
      article, we present a method of cerebrovascular casting that produces a durable
      skeleton of the entire vascular bed, including arteries, veins, and capillaries
      that may be analyzed using many different modalities. Complete casting of the
      microvessels of the mouse cerebrovasculature can be difficult; however, these
      challenges are addressed in this step-by-step protocol. Through intracardial
      perfusion of the vascular casting material, all vessels of the body are casted.
      The brain can then be removed and clarified using the organic solvent methyl
      salicylate. Three dimensional imaging of the brain blood vessels can be
      visualized simply and inexpensively with any conventional brightfield microscope
      or dissecting microscope. The casted cerebrovasculature can also be imaged and
      quantified using micro-computed tomography (micro-CT)(1). In addition, after
      being imaged, the casted brain can be embedded in paraffin for histological
      analysis. The benefit of this vascular casting method as compared to other
      techniques is its broad adaptation to various analytic tools, including
      brightfield microscopic analysis, CT scanning due to the radiopaque
      characteristic of the material, as well as histological and immunohistochemical
      analysis. This efficient use of tissue can save animal usage and reduce costs. We
      have recently demonstrated application of this method to visualize the irregular
      blood vessels in a mouse model of adult BAVM at a microscopic level(2), and
      provide additional images of the malformed vessels imaged by micro-CT scan.
      Although this method has drawbacks and may not be ideal for all types of
      analyses, it is a simple, practical technique that can be easily learned and
      widely applied to vascular casting of blood vessels throughout the body.

PMID- 22143105
TI  - Comparative electrochemical study of superoxide reductases.
AB  - Superoxide reductases are involved in relevant biological electron transfer
      reactions related to protection against oxidative stress caused by reactive
      oxygen species. The electrochemical features of metalloproteins belonging to the
      three different classes of enzymes were studied by potentio-dynamic techniques
      (cyclic and square wave voltammetry): desulfoferrodoxin from Desulfovibrio
      vulgaris Hildenborough, class I superoxide reductases and neelaredoxin from
      Desulfovibrio gigas and Treponema pallidum, namely class II and III superoxide
      reductases, respectively. In addition, a small protein, designated desulforedoxin
      from D. gigas, which has high homology with the N-terminal domain of class I
      superoxide reductases, was also investigated. A comparison of the redox
      potentials and redox behavior of all the proteins is presented, and the results
      show that SOR center II is thermodynamically more stable than similar centers in
      different proteins, which may be related to an intramolecular electron transfer
      function.

PMID- 22143106
TI  - Effects of hypoxic living and training on gene expression in an obese rat model.
AB  - PURPOSE: The study's purpose was to determine in a rat obesity model the effects
      of normoxic training, sedentary hypoxic living, or hypoxic living plus training
      on the skeletal muscle messenger RNA (mRNA) levels of 14 genes involved in oxygen
      sensing (hypoxia-inducible factor 1alpha, vascular endothelial growth factor,
      myoglobin), glucose metabolism (glucose transporter 4, muscle
      phosphofructokinase), mitochondrial biogenesis (peroxisome proliferator-activated
      receptor gamma coactivator 1-alpha, nuclear respiratory factor 1) and function
      (citrate synthase, mitochondrial-encoded cytochrome oxidase subunit 1), pH
      regulation (monocarboxylate transporter 1, carbonic anhydrase 3), and antioxidant
      defense (manganese superoxide dismutase, copper/zinc superoxide dismutase,
      glutathione S-transferase pi). METHODS: One hundred thirty male 3-wk-old Sprague
      Dawley rats were fed a high-fat diet (4100 kcal.kg(-1)) for 3 months (all
      reaching a final weight >415 g) and then randomly assigned to the following
      groups (n = 10 per group): C (control, 2 d of sedentary living in normoxic
      conditions), TN1-TN4 (1-4 wk of normoxic treadmill training), SH1-SH4 (1-4 wk of
      sedentary hypoxic living (13.6% O2)), or TH1-TH4 (1-4 wk of hypoxic living (13.6%
      O2) + hypoxic treadmill training). Individual mRNA levels recorded for TN1-TN4,
      SH1-SH4, and TH1-TH4 were expressed relative to the mean obtained in C for each
      gene. RESULTS: Through a two-way ANOVA, a significant interaction (treatment *
      treatment duration) effect was detected on expression levels of mRNAs for hypoxia
      inducible factor 1alpha, vascular endothelial growth factor, myoglobin, nuclear
      respiratory factor 1, citrate synthase, carbonic anhydrase 3, monocarboxylate
      transporter 1, copper/zinc superoxide dismutase, glutathione S-transferase pi,
      and manganese superoxide dismutase. Expression levels were overall highest when
      training and living under hypoxia, usually after 3 wk (TH3), i.e., 79%-99% higher
      than the lowest values (usually corresponding to TN2) and 15.5%-53.9% higher than
      the second highest values (usually TH4). Normoxic training elicited no greater
      response than hypoxic sedentary living. CONCLUSIONS: In our obese rat model,
      hypoxic living conditions, especially if accompanied by hypoxic exercise
      training, can lead to health-related molecular adaptations at the skeletal muscle
      level.

PMID- 22143107
TI  - Effects of eccentrically biased versus conventional weight training in older
      adults.
AB  - INTRODUCTION: We compared the effects of eccentrically biased (EB) and
      conventional (CONV) resistance training on muscle architecture, one-repetition
      maximum (1RM), isometric strength, isokinetic force-velocity characteristics,
      functional capacity, and pulse wave velocity in older men and women. METHODS:
      Twenty-eight older adults participated in the study (mean +/- SD: age = 68 +/- 5
      yr). Of these, 13 were allocated to a waitlist control, 10 of whom progressed to
      training (CONV, n = 12; EB, n = 13). Training was twice a week for 16 wk. EB
      involved three sets of 10 concentric lifts at 50% of 1RM with the eccentric
      portion of repetitions performed unilaterally, alternating between limbs with
      each repetition. CONV involved two sets of 10 repetitions at 75% of 1RM. EB and
      CONV were matched for total work. Isokinetic knee extensor strength was assessed
      across a range of velocities (0-360 degrees .s(-1)). Functional capacity was
      assessed via a 6-m fast walk test, a timed up and go test, stair climb and
      descent power test, and vertical jump test. Vastus lateralis and gastrocnemius
      medialis architecture were assessed using ultrasonography. RESULTS: Both EB and
      CONV improved 1RM (Delta 23%-35%, P < 0.01). Compared to the control group, both
      training regimens improved 6-m fast walk (Delta 5%-7%, P < 0.01) and concentric
      torque at 60 and 120 degrees .s(-1) (Delta 6%-8%, P < 0.05). Significant
      improvements were evident in EB for isometric and concentric torque at 240 and
      360 degrees .s(-1) (Delta 6%-11%, P < 0.05), vastus lateralis thickness (Delta
      5%, P < 0.05), and stair climb (Delta 5%, P < 0.01). Timed up and go (Delta 5%, P
      < 0.01), stair descent (Delta 4%, P < 0.05), and vertical jump (Delta 7%, P <
      0.01) improved in CONV. Pulse wave velocity, pennation angle, and fascicle length
      remained unchanged in both training groups. CONCLUSIONS: EB seems superior to
      CONV at increasing torque at high contraction velocities, whereas CONV seems more
      effective at improving some functional performance measures and vertical jump.
      This has important implications for preserving functional capacity.

PMID- 22143108
TI  - Exercise during pregnancy and the gestational age distribution: a cohort study.
AB  - PURPOSE: The study's purpose was to examine the associations between exercise
      performed at different time points during pregnancy and gestational age (GA) in a
      population-based cohort study. METHODS: Data included 61,098 singleton
      pregnancies enrolled between 2000 and 2006 in the Norwegian Mother and Child
      Cohort Study, conducted by the Norwegian Institute of Public Health. Self
      reported exercise was collected from two questionnaires in pregnancy weeks 17 and
      30. GA was determined on the basis of the expected date of delivery according to
      ultrasound, as registered in the Medical Birth Registry of Norway. We used
      logistic regression to analyze preterm (<37 completed weeks) and postterm births
      (>= 42 wk). Comparison of mean GA by exercise levels was estimated by a general
      linear model. RESULTS: Mean GA for women exercising three to five times a week in
      week 17 was 39.51 (95% confidence interval [CI] = 39.48-39.54) compared with
      39.34 (95% CI = 39.30-39.37) completed weeks for nonexercisers (P < 0.001). Mean
      differences remained for all categories of exercise after adjusting for
      confounding with the greatest mean difference between exercising three to five
      times per week in week 17 and nonexercisers (equals 1 d). Similar mean
      differences in GA were observed by exercise levels in week 30. The greatest
      protective effect on risk of preterm birth was observed for women exercising
      three to five times a week in week 17 or 30 (adjusted odds ratio (aOR) = 0.82,
      95% CI = 0.73-0.91 and aOR = 0.74, 95% CI = 0.65-0.83, respectively) compared
      with nonexercisers. On the other hand, women exercising one to two or three to
      five times per week in week 17 were slightly more likely to have a postterm birth
      (aOR = 1.14, 95% CI = 1.04-1.24 and aOR = 1.15, 95% CI = 1.04-1.26,
      respectively). Mean GA did not differ by type of exercise performed during
      pregnancy. CONCLUSIONS: Exercise performed during pregnancy shifted the GA
      distribution slightly upward resulting in reduced preterm births and slightly
      increased postterm births.

PMID- 22143109
TI  - Health promotion in older Chinese: a 12-month cluster randomized controlled trial
      of pedometry and "peer support".
AB  - PURPOSE: Aging, in conjunction with decreasing physical activity, is associated
      with a range of health problems. Simple, low-maintenance, population-based means
      of promoting activity to counteract the age-associated decline are required. We
      therefore assessed the effect of pedometry and buddy support to increase physical
      activity. METHODS: We undertook a clustered randomized trial (HKCTR-346) of 24
      community centers involving 399 older Chinese participants (>= 60 yr). Centers
      were randomly allocated to 1) pedometry and buddy, 2) pedometry and no buddy, 3)
      no pedometry and buddy, and 4) no pedometry and no buddy with a 2 * 2 factorial
      design. The trial simultaneously tested the individual and combined effects of
      the interventions. The intervention groups also received monthly organized group
      activities to provide encouragement and support. Outcome measures were assessed
      at 6 and 12 months, including physical fitness and activity and cardiovascular
      disease risk factors (anthropometry and blood pressure). RESULTS: From the 24
      centers, 356 volunteers (89.2%) completed the study. Those receiving the
      interventions had higher mean physical activity levels at 12 months of 1820 (95%
      confidence interval (CI) = 1360-2290) and 1260 (95% CI = 780-1740) MET.min.wk(
      1), respectively relative to the decrease in the control groups. The buddy peer
      support intervention significantly improved mean aerobic fitness (12% [95% CI =
      4%-21%]) and reduced both body fat (-0.6% [95% CI = -1.1% to 0.0%]) and time to
      complete the 2.5-m get-up-and-go test (-0.27 [95% CI = -0.53 to -0.01] s). No
      other improvements in the cardiovascular disease risk factors were observed. The
      combination of motivational tools was no better than the individual
      interventions. CONCLUSIONS: Both motivational interventions increased physical
      activity levels, and the buddy style improved fitness. These tools could be
      useful adjuncts in the prevention of obesity and age-related complications.

PMID- 22143110
TI  - Aerodynamic drag modeling of alpine skiers performing giant slalom turns.
AB  - PURPOSE: Aerodynamic drag plays an important role in performance for athletes
      practicing sports that involve high-velocity motions. In giant slalom, the skier
      is continuously changing his/her body posture, and this affects the energy
      dissipated in aerodynamic drag. It is therefore important to quantify this energy
      to understand the dynamic behavior of the skier. The aims of this study were to
      model the aerodynamic drag of alpine skiers in giant slalom simulated conditions
      and to apply these models in a field experiment to estimate energy dissipated
      through aerodynamic drag. METHODS: The aerodynamic characteristics of 15
      recreational male and female skiers were measured in a wind tunnel while holding
      nine different skiing-specific postures. The drag and the frontal area were
      recorded simultaneously for each posture. Four generalized and two individualized
      models of the drag coefficient were built, using different sets of parameters.
      These models were subsequently applied in a field study designed to compare the
      aerodynamic energy losses between a dynamic and a compact skiing technique.
      RESULTS: The generalized models estimated aerodynamic drag with an accuracy of
      between 11.00% and 14.28%, and the individualized models estimated aerodynamic
      drag with an accuracy between 4.52% and 5.30%. The individualized model used for
      the field study showed that using a dynamic technique led to 10% more aerodynamic
      drag energy loss than using a compact technique. DISCUSSION: The individualized
      models were capable of discriminating different techniques performed by advanced
      skiers and seemed more accurate than the generalized models. The models presented
      here offer a simple yet accurate method to estimate the aerodynamic drag acting
      upon alpine skiers while rapidly moving through the range of positions typical to
      turning technique.

PMID- 22143113
TI  - A prospective study of sedentary behavior in a large cohort of youth.
AB  - PURPOSE: The study's purpose was to describe longitudinal patterns of objectively
      measured sedentary behavior from age 12 to 16. METHODS: Children participating in
      the Avon Longitudinal Study of Parents and Children wore accelerometers for 1 wk
      at ages 12, 14, and 16. Participants included boys (n = 2591) and girls (n =
      2845) living in a single geographic location in the United Kingdom (Bristol).
      Total minutes per day spent in sedentary behavior and time spent in blocks of
      sedentary behavior lasting 10-19, 20-29, and >= 30 min are described. Growth
      curve models were used to determine the rate of change in sedentary behavior from
      age 12 to 16. RESULTS: At age 12, the boys and girls, on average, were sedentary
      for 418.0 +/- 67.7 and 436.6 +/- 64.0 min.d(-1), respectively, and sedentary
      behavior increased over time to 468.0 +/- 74.3 and 495.6 +/- 68.9 min.d(-1) at
      age 14 and to 510.4 +/- 76.6 and 525.4 +/- 67.4 min.d(-1) at age 16. Growth curve
      analyses found that total sedentary behavior increased at a rate of 19.5 +/- 0.7
      and 22.8 +/- 0.7 min.d(-1).yr for the boys and girls, respectively. The absolute
      mean increase in total sedentary behavior (+92.4 and +88.8 min.d(-1) for the boys
      and girls, respectively) closely matched the mean decrease in light physical
      activity (-82.2 and -82.9 min.d(-1) for the boys and girls, respectively) from
      age 12 to 16. Time spent in continuous sedentary behavior lasting >= 30 min
      increased by 121% from age 12 to 16. CONCLUSIONS: Sedentary behavior increased
      with age, at the expense of light physical activity. The increase in sedentary
      behavior lasting >= 30 min in duration contributed greatly to the increase in
      total sedentary behavior.

PMID- 22143114
TI  - Use of a two-regression model for estimating energy expenditure in children.
AB  - PURPOSE: The purpose of this study was to develop two new two-regression models
      (2RM), for use in children, that estimate energy expenditure (EE) using the
      ActiGraph GT3X: 1) mean vector magnitude (VM) counts or 2) vertical axis (VA)
      counts. The new 2RMs were also compared with existing ActiGraph equations for
      children. METHODS: Fifty-seven boys and 52 girls (mean +/- SD: age = 11 +/- 1.7
      yr, body mass index = 21.4 +/- 5.5 kg.m(-2)) performed 30-min supine rest and 8
      min of six different activities ranging from sedentary behaviors to vigorous
      physical activity. Eighteen activities were split into three routines with each
      routine performed by 38-39 participants. Seventy-seven participants were used for
      the development group, and 39 participants were used for the cross-validation
      group. During all testing, activity data were collected using an ActiGraph GT3X,
      worn on the right hip, and oxygen consumption was measured using a Cosmed K4b.
      All energy expenditure values are expressed as MET(RMR) (activity VO(2)/resting
      VO(2)). RESULTS: For each activity, a coefficient of variation was calculated
      using 10-s epochs for the VA and VM to determine whether the activity was
      continuous walking/running or an intermittent lifestyle activity. Separate
      regression equations were developed for walking/running and intermittent
      lifestyle activity. In the cross-validation group, the VM and VA 2RMs were within
      0.8 MET(RMR) of measured MET(RMR) for all activities except Sportwall and running
      (all P > 0.05). The other existing ActiGraph equations had mean errors ranging
      from 0.0 to 2.6 MET(RMR) for the activities. CONCLUSIONS: The new 2RMs for use in
      children with the ActiGraph GT3X provide a closer estimate of mean measured
      MET(RMR) than other currently available prediction equations. In addition, they
      improve the individual prediction errors across a wide range of activity
      intensities.

PMID- 22143116
TI  - Antimicrobial resistance in sexually transmitted infections in the developed
      world:  implications for rational treatment.
AB  - PURPOSE OF REVIEW: Public health control of bacterial sexually transmitted
      infections (STIs) is dependent on the delivery of effective therapy and so will
      be compromised by the emergence of resistance. The scope of the problem and the
      implications for treatment that follow are discussed in this review. RECENT
      FINDINGS: Emerging resistance has been documented in all the bacterial STIs, but
      is considered rare and unconfirmed in Chlamydia trachomatis whereas is of global
      concern in Neisseria gonorrhoeae. Azithromycin resistance has now been recognized
      in Mycoplasma genitalium, Treponema pallidum and N. gonorrhoeae, questioning its
      widespread use for chlamydial infection and threatening its future use. Rapidly
      increasing levels of decreased susceptibility to the extended-spectrum
      cephalosporins in N. gonorrhoeae and emerging treatment failures to both cefixime
      and ceftriaxone, without an obvious alternative agent, are of considerable
      concern. Implications for treatment include choice and timing of any change in
      therapy, reintroduction of test of cure and definition of treatment failure in an
      era of molecular testing. SUMMARY: Emerging resistance in all bacterial STIs and
      the particular problem of resistant gonorrhoea will present a challenge to
      maintain antimicrobial therapy at the forefront of public health control.

PMID- 22143115
TI  - Herpes simplex virus-2 in the genital mucosa:  insights into the mucosal host
      response and vaccine development.
AB  - PURPOSE OF REVIEW: Herpes simplex virus (HSV)-2 is the predominant cause of
      genital herpes and has been implicated in HIV infection and transmission. Thus
      far, vaccines developed against HSV-2 have been clinically ineffective in
      preventing infection. This review aims to summarize the innate and adaptive
      immune responses against HSV-2 and examines the current status of vaccine
      development. RECENT FINDINGS: Both innate and adaptive immune responses are
      essential for an effective primary immune response and the generation of
      immunity. The innate response involves Toll-like receptors, natural killer cells,
      plasmacytoid dendritic cells, and type I, II, and III interferons. The adaptive
      response requires a balance between CD4+ and CD8+ T-cells for optimal viral
      clearance. T-regulatory cells may be involved, although their exact function has
      yet to be determined. Current vaccine development involves the use of HSV-2
      peptides or attenuated/replication-defective HSV-2 to generate adaptive anti-HSV
      2 immune responses, however the generation of innate responses may also be an
      important consideration. SUMMARY: Although vaccine development has primarily
      focused on the adaptive response, arguments for innate involvement are emerging.
      A greater understanding of the innate and adaptive processes underlying the
      response to HSV-2 infection will provide the foundation for the development of an
      effective vaccine.

PMID- 22143117
TI  - Vaccination against sexually transmitted infections.
AB  - PURPOSE OF REVIEW: This review discusses the vaccines available for the
      prevention of sexually transmitted infections (STIs), and focuses on the
      contribution of these vaccines to the control of three infections: hepatitis A,
      hepatitis B and human papillomavirus (HPV). RECENT FINDINGS: Hepatitis A is an
      STI in men who have sex with men (MSM). The introduction of the vaccine has
      resulted in the almost complete disappearance of epidemics of infection despite
      vaccine coverage of only 30-50% in MSM. In contrast hepatitis B infection sexual
      transmission both in MSM and heterosexuals continues at low but significant
      levels despite similar vaccine coverage. The two HPV vaccines are highly
      effective for the HPV types they contain, and for some related HPV types.
      Countries using the quadrivalent vaccine have experienced dramatic falls in
      genital warts in younger women, and to a lesser degree in heterosexual men but
      not homosexual men. SUMMARY: Vaccines for hepatitis A, B and HPV have been highly
      effective in controlling STI at a community level.

PMID- 22143118
TI  - Human papillomavirus vaccine and men:  what are the obstacles and challenges?
AB  - PURPOSE OF REVIEW: The present review describes the indications for vaccinating
      men with the quadrivalent human papillomavirus (HPV) vaccine, reports on the US
      rates of male vaccination, and reviews the recent research on acceptability of
      vaccinating men and research on the cost-effectiveness of adding men to existing
      female HPV immunization programs. RECENT FINDINGS: Recent evidence shows that the
      quadrivalent HPV vaccine prevents several HPV-related diseases in men. However,
      despite the licensure of the vaccine in the USA for men 9 through 26 years of
      age, rates of male vaccination are very low. Research on acceptability, in
      general, indicates strong interest in vaccination among men, parents, and
      healthcare providers, though female vaccination is typically seen as a higher
      priority. Cost-effectiveness studies indicate that in the context of modest
      female vaccination rates and with the specification of a broad range of disease
      outcomes (e.g. genital warts, anogenital cancers, and oropharyngeal cancers),
      male vaccination can be quite cost-effective. SUMMARY: Men are at high risk for
      HPV infection and can benefit from vaccination, but vaccination rates among men
      remain extremely low. More research needs to be done on the predictors of uptake
      of HPV vaccine among men and on the development of interventions to increase male
      vaccination.

PMID- 22143119
TI  - GaAs 904-nm laser irradiation improves myofiber mass recovery during regeneration
      of skeletal muscle previously damaged by crotoxin.
AB  - This work investigated the effect of gallium arsenide (GaAs) irradiation (power:
      5 mW; intensity: 77.14 mW/cm(2), spot: 0.07 cm(2)) on regenerating skeletal
      muscles damaged by crotoxin (CTX). Male C57Bl6 mice were divided into six groups
      (n = 5 each): control, treated only with laser at doses of 1.5 J or 3 J, CTX
      injured and, CTX-injured and treated with laser at doses of 1.5 J or 3 J. The
      injured groups received a CTX injection into the tibialis anterior (TA) muscle.
      After 3 days, TA muscles were submitted to GaAs irradiation at doses of 1.5 or 3
      J (once a day, during 5 days) and were killed on the eighth day. Muscle
      histological sections were stained with hematoxylin and eosin (H&E) in order to
      determine the myofiber cross-sectional area (CSA), the previously injured muscle
      area (PIMA) and the area density of connective tissue. The gene expression of
      MyoD and myogenin was detected by real-time PCR. GaAs laser at a dose of 3 J, but
      not 1.5 J, significantly increased the CSA of regenerating myofibers and reduced
      the PIMA and the area density of intramuscular connective tissue of CTX-injured
      muscles. MyoD gene expression increased in the injured group treated with GaAs
      laser at a dose of 1.5 J. The CTX-injured, 3-J GaAs laser-treated, and the CTX
      injured and treated with 3-J laser groups showed an increase in myogenin gene
      expression when compared to the control group. Our results suggest that GaAs
      laser treatment at a dose of 3 J improves skeletal muscle regeneration by
      accelerating the recovery of myofiber mass.

PMID- 22143120
TI  - Revealing the true crystal structure of L-phenylalanine using solid-state density
      functional theory.
AB  - Solid-state density functional theory can be used for crystal structure
      determination from powder X-ray diffraction data of molecular crystals that are
      too large and complex for conventional refinement methods.

PMID- 22143121
TI  - Burkitt-like lymphoma arising in the thyroid gland.
AB  - INTRODUCTION: Primary Burkitt lymphoma of the thyroid gland is exceptionally
      rare. This highly aggressive, potentially curable malignancy arises from B cells.
      It presents as a rapidly expanding thyroid mass causing compressive symptoms.
      This article reports a very rare occurrence of Burkitt-like lymphoma in the
      thyroid, a variant of Burkitt lymphoma. METHODS: A 60-year-old white female
      developed a rapidly expanding thyroid mass associated with airway compression and
      difficulty in swallowing. RESULTS: Fine needle aspiration and cytometry studies
      established the diagnosis of lymphoma. The patient underwent an incisional neck
      biopsy which confirmed the final diagnosis according to the latest World Health
      Organization criteria. It was successfully treated with 1 cycle of appropriate
      therapeutic chemotherapy. CONCLUSION: In patients with lymphoma diagnosed on fine
      needle aspiration, an incisional thyroid and bone marrow biopsies are required to
      aid in the diagnosis and assure the appropriate chemotherapy protocol.

PMID- 22143122
TI  - Delayed renal function recovery from drug-induced acute interstitial nephritis.
AB  - INTRODUCTION: Acute interstitial nephritis, considered one of the major causes of
      reversible acute kidney injury, was frequently encountered as drug-treatment
      complication in the early stage of infection control. In some cases, drug-induced
      acute interstitial nephritis (DIAIN) resulted in delayed function recovery or
      chronic kidney disease. To study the underlying mechanism, the authors
      investigated the clinical and pathological features of DIAIN patients with
      delayed renal function recovery. The delayed recovery group consisted of patients
      with reduced renal function for more than 3 months after diagnosis. METHODS: In
      this retrospective study, 18 patients with DIAIN from January 2003 to December
      2009 were identified as the delayed recovery group, whereas 54 patients with
      DIAIN who recovered completely within 3 months were treated as the control group.
      Clinical and pathological features were compared between the 2 groups. RESULTS:
      In the delayed recovery group, the average age at onset was 48.8 years,
      antibiotics and herbs were the 2 main causative drugs and the dominant extra
      renal manifestation was gastrointestinal symptomatology. In comparison with
      patients in the control group, patients in the delayed recovery group had longer
      interval time from disease onset to hospitalization, and they presented with less
      oliguria. Moreover, these patients had higher levels of urine retinol binding
      protein, and more renal interstitial inflammatory cell infiltrations were
      observed in their renal histology. CONCLUSION: Aging, long interval time from
      disease onset to hospitalization and renal interstitial inflammatory cell
      infiltration may predict delayed renal function recovery.

PMID- 22143123
TI  - Airway ultraflex stenting in esophageal cancer with esophagorespiratory fistula.
AB  - INTRODUCTION: Esophagorespiratory fistula (ERF) caused by esophageal cancer has a
      poor prognosis. This study describes the clinical effects of airway ultraflex
      stenting as an alternative method for ERF caused by esophageal cancer. METHODS:
      In an university-affiliated hospital, consecutive patients with ERF caused by
      esophageal cancer and confirmed by bronchoscopy were included. The demography,
      clinical manifestations and survival between groups with and without airway
      stenting were compared by case-control study. RESULTS: From 2001 to 2007, 817
      patients with esophageal cancer received bronchoscopy. Among these patients, 59
      patients with ERF were included in this study. The demography and clinical
      manifestations between groups with and without airway stenting were similar, but
      survival improved in group with airway stenting, which was compared using log
      rank test [P = 0.04; hazard ratio, 0.56; 95% confidence interval (CI), 0.31
      0.99]. After adjusted with age and gender by multinominal logistic regression,
      airway stenting [adjusted odds ratio (OR), 5.2; P = 0.01; 95% CI, 1.4-18.8],
      performance status (adjusted OR, 6.1; P = 0.004; 95% CI, 1.8-20.8), further
      treatment (adjusted OR, 8.7; P = 0.001; 95% CI, 2.3-32.8) and prolonged pneumonia
      (adjusted OR, 0.14; P = 0.008; 95% CI, 0.03-0.59) remained as significant factors
      that impacted survival. CONCLUSIONS: Surgical treatment remains the first choice
      in patients with esophageal cancer with ERF; however, the authors provided an
      alternative airway stenting for those patients whom surgery is unsuitable. It
      improved survival in the group with airway stenting than those without.
      Performance status improvement and further treatment for esophageal cancer may
      improve survival, but prolonged pneumonia may worsen survival.

PMID- 22143124
TI  - Predictive value of acute kidney injury in medical intensive care patients with
      sepsis originating from different infection sites.
AB  - INTRODUCTION: Sepsis is the most common noncoronary cause of mortality in
      intensive care units (ICUs). This study compared different systems for predicting
      outcomes in a population of critically ill patients with sepsis originating from
      different infection sites, including intra-abdominal and pulmonary infections.
      METHODS: This post hoc analysis of an accumulated database enrolled 161
      heterogeneous critically ill patients diagnosed as severe sepsis and septic shock
      patients admitted to medical ICUs from June 2005 to May 2007. Demographic
      characteristics, clinical and laboratory variables, comorbidities and infection
      source were prospectively recorded on the first day of ICU admission. Patient
      evaluations included acute physiology and chronic health evaluation (APACHE) II,
      APACHE III, sequential organ failure assessment scores, organ system failure and
      risk of renal failure, injury to kidney, failure of kidney function, loss of
      kidney function and end-stage renal failure (RIFLE) classification. RESULTS:
      Regarding the different originating sites of severe sepsis, intra-abdominal
      infections and pulmonary infections had the highest mortality rates (83.3% and
      48.5%, respectively; P < 0.001). The APACHE III was the best mortality predictor
      for the overall sepsis population [areas under the receiver operating
      characteristic curve (AUROC) 0.800], whereas RIFLE classification was the best
      predictor in those with intra-abdominal infection (AUROC 0.856). The AUROC
      analyses verified that RIFLE classification had significantly (P < 0.05) better
      discriminatory power for predicting hospital mortality in patients with intra
      abdominal infections than in those with pulmonary infections (AUROC 0.545).
      CONCLUSIONS: This investigation confirms that different infection sites have
      different outcomes. In terms of mortality prediction, outcome scoring systems are
      significantly more accurate in patients with intra-abdominal infections than in
      those with pulmonary infections.

PMID- 22143125
TI  - Asymmetric production of nitric oxide in mouse primary cortical mixed glial cell
      cultures treated with lipopolysaccharide.
AB  - Activated glial cells produce many toxic molecules, including cytokines and
      nitric oxide (NO). There is evidence that excess NO production plays a key role
      in neuronal cell death. Previous research has demonstrated that cortical glial
      cells from the left and right cortices of the brain secrete cytokines
      asymmetrically. However, no evidence to date exists about whether glial cell
      produced NO is produced asymmetrically as well. The results of this study show
      that NO production and inducible NO synthase gene expression are both
      significantly higher in the right hemisphere-derived mixed glial cell compared
      with cultures derived from the left.

PMID- 22143126
TI  - Warfarin resistance associated with parenteral nutrition.
AB  - Warfarin is widely used as an oral anticoagulant for the prevention and long-term
      treatment of venous thromboembolism and for the prevention of thromboembolic
      complications associated with atrial fibrillation, heart valve replacement and
      myocardial infarction. Warfarin exerts its anticoagulation effect by inhibiting
      the enzymes responsible for the cyclic interconversion of vitamin K in the liver.
      Vitamin K serves as a cofactor required for the carboxylation of the vitamin K
      dependent coagulation proteins. By inhibiting the supply of vitamin K in the
      production of these proteins, warfarin indirectly slows their rate of synthesis.
      The authors describe a 46-year-old patient readily anticoagulated for a deep
      venous thrombosis who then required large doses of warfarin after initiation of
      total parenteral nutrition, which included lipid preparation that contained
      vitamin K, in addition to vitamin K required for the daily parenteral nutrition.
      The effect of total parenteral nutrition with vitamin K on anticoagulation is
      discussed.

PMID- 22143127
TI  - Bilateral inferior accessory fissures in lungs.

PMID- 22143128
TI  - Thyroid hormone levels predict mortality in intensive care patients with
      cirrhosis.
AB  - INTRODUCTION: Mortality rates of intensive care patients are quite high. The aim
      of this study was to determine the availability of thyroid function tests and
      predictive scoring systems on the outcome of cirrhotic patients admitted to the
      intensive care unit. METHODS: A total of 106 patients were included in the final
      analysis, of which 32 were men (30.2%) and 74 were women (69.8%). Predictors of
      mortality that were investigated include acute physiology and chronic health
      evaluation (APACHE II), model for end-stage liver disease (MELD), Child-Turcotte
      Pugh (CTP) and sequential organ failure assessment (SOFA) scores and thyroid
      function tests including free triiodo-L-thryronin (fT3), free
      tetraiodothyronine/thyroxine (fT4) and thyroid-stimulating hormone/thyrotropin
      (TSH) levels. RESULTS: High APACHE II, MELD, CTP and SOFA score and suppression
      of fT3 were all found to be associated with higher mortality in our intensive
      care patients who have cirrhosis (P < 0.001). Suppression of fT3 was also found
      to be reciprocally correlated with high APACHE II, MELD, CTP and SOFA scores (P <
      0.001). fT4 had also reciprocal correlation with APACHE II, MELD, CTP and
      mortality. There is no correlation between TSH levels and predictive scores or
      mortality. CONCLUSIONS: Calculation of APACHE II, MELD, CTP and SOFA scores and
      measurement of fT3 and fT4 levels may all be useful as predictors of mortality in
      intensive care patients who have cirrhosis.

PMID- 22143129
TI  - Sister Mary Joseph's nodule originating from primary duodenal adenocarcinoma.

PMID- 22143130
TI  - Fasciitis ossificans of the breast.

PMID- 22143131
TI  - Isolated septic arthritis of the hip secondary to Fusobacterium necrophorum.
AB  - Septic arthritis secondary to Fusobacterium necrophorum is rare and may be
      related to Lemierre syndrome which classically presents as pharyngitis in young
      adults, followed by a septicemic illness characterized by internal jugular vein
      thrombosis and metastatic infection. However, there were only 5 case reports of
      isolated septic arthritis caused by F. necrophorum in previous literature. The
      authors reviewed the literature and report a 24-year-old woman who delayed
      presentation to the emergency department and was eventually diagnosed with
      isolated septic arthritis of the hip caused by F. necrophorum. Her condition was
      complicated by severe sepsis and treated with aggressive resuscitation,
      vasopressor, antibiotics and an open arthrotomy with repeated drainage.
      Eventually, her hip bone was destroyed and she required a joint replacement.

PMID- 22143132
TI  - Ectopic, polycystic and stoned:  pelvic kidney in a patient with autosomal
      dominant polycystic kidney disease.

PMID- 22143133
TI  - The microbiota of the vagina and its influence on women's health and disease.
AB  - Explorations of the vaginal microbiota (VMB) began over 150 years ago. Using
      light microscopy and bacterial cultures, the concept of normal versus abnormal
      microbiota in women began to emerge. The latter became known by the term
      "bacterial vaginosis" (BV). BV microbiota is dominated by Gardnerella vaginalis
      and includes a number of anaerobic organisms. In contrast, normal flora is
      dominated by various Lactobacilli. BV microbiota is associated with vaginal
      discharge, poor pregnancy outcomes, pelvic inflammatory disease, postoperative
      wound infections and endometritis after elective abortions. In addition, BV flora
      predisposes women to infection by human immunodeficiency virus and sexually
      transmitted diseases. Application of molecular techniques over the past decade
      has significantly advanced our understanding of the VMB. It is far more complex
      than previously recognized and is composed of many previously unknown organisms
      in addition to those already identified by culture. Analyses using high
      throughput sequencing techniques have revealed unique microbial communities not
      previously recognized within the older, established vaginal flora categories.
      These new findings will inform the design of future clinical investigations of
      the role of the VMB in health and disease.

PMID- 22143135
TI  - Chemotherapy: New FluCam combination therapy has familiar limitations.

PMID- 22143137
TI  - Neurosurgical management of metastases in the central nervous system.
AB  - Metastases in the central nervous system (CNS) are identified in up to 30% of
      patients at autopsy. Rates of CNS involvement in metastatic cancer are believed
      to be increasing, possibly owing to better control of systemic disease with novel
      chemotherapies or improved metastasis detection. The neurosurgical treatment of
      patients with metastatic cancer is an integral component of multimodality therapy
      for brain and spinal metastases. Survival benefit has been demonstrated for the
      addition of open surgery as well as the use of stereotactic radiosurgery (SRS) to
      whole-brain radiation therapy for treatment of patients with isolated cranial and
      spinal metastases compared with whole-brain radiation therapy alone. New clinical
      trials that directly compare open surgical procedures with SRS are underway, as
      are trials examining the role of neurosurgical procedures, such as vertebroplasty
      and kyphoplasty, in association with radiotherapy as methods for pain control in
      cancer patients with metastatic lesions in the spinal column. In this article, I
      review data from current randomized clinical trials that examine the role of
      neurosurgical intervention in the treatment of patients with CNS metastases.

PMID- 22143138
TI  - Skin cancer: Novel resistance mechanism revealed.

PMID- 22143141
TI  - Screening: Smile, they're taking a SNaPshot of your cancer-causing genes.

PMID- 22143140
TI  - Practical implications of gene-expression-based assays for breast oncologists.
AB  - Gene-expression profiling has had a considerable impact on our understanding of
      breast cancer biology, and more recently on clinical care. Two statistical
      approaches underlie these advancements. Supervised analyses have led to the
      development of gene-expression signatures designed to predict survival and/or
      treatment response, which has resulted in the development of new clinical assays.
      Unsupervised analyses have identified numerous biological signatures including
      signatures of cell type of origin, signaling pathways, and of cellular
      proliferation. Included within these biological signatures are the molecular
      subtypes known as the 'intrinsic' subtypes of breast cancer. This classification
      has expanded our appreciation of the heterogeneity of breast cancer and has
      provided a way to sub-classify the disease in a manner that might have clinical
      utility. In this Review, we discuss the clinical utility of gene-expression-based
      assays and their technical potential as clinical tools vis-a-vis the performance
      of breast cancer biomarkers that are the current standard of care.

PMID- 22143142
TI  - Role of randomized phase III trials in an era of effective targeted therapies.
AB  - In the era of cytotoxic therapies, tumor regression has rarely been observed in
      phase I trials and randomized controlled trials have usually been required to
      demonstrate modest improvements over prevailing standards of care. In the era of
      effective targeted therapies, drugs such as vemurafenib and crizotinib have
      demonstrated convincing efficacy in early clinical testing, raising the question
      of whether randomized phase III trials are necessary and feasible before drug
      approval. Since 1992, the FDA has approved a number of drugs without data from
      confirmatory clinical trials as part of the accelerated approval process. While
      this initiative has largely been successful in bringing effective drugs to the
      market more quickly, there is much to be learned from case studies of drugs, such
      as gefitinib, which subsequently failed to gain full approval. In this Review, we
      use a number of historical examples to make the case that it may be reasonable to
      consider foregoing randomized phase III trials for certain drugs before drug
      approval. We explore the consequences (both good and bad) of foregoing randomized
      phase III trials and propose criteria that might be used to select drugs for
      consideration of such an approach.

PMID- 22143144
TI  - Breast cancer: Should we assess HER2 status by Oncotype DX?

PMID- 22143145
TI  - Clinical and epidemiological issues in mammographic density.
AB  - High mammographic density is associated with an increased risk of breast cancer,
      and of all known breast cancer risk factors has the greatest attributable
      fraction. Mammographic density is estimated to account for 16% of all breast
      cancers, but can be altered by endogenous and exogenous hormonal factors, and
      generally declines with age. Confounding factors such as age, parity, menopausal
      status and BMI make the interpretation of mammographic density particularly
      challenging. Furthermore, none of the established means of measuring mammographic
      density are entirely satisfactory because they are time consuming or subjective.
      It is hoped that by adding information regarding mammographic density to existing
      models of breast cancer risk assessment, the accuracy of individual risk
      assessments can be improved. Although mammographic density has clearly been shown
      to be a powerful factor for predicting the risk of developing breast cancer, its
      potential role in assessing hormonal preventive regimens and helping to tailor
      screening algorithms cannot be fully realized until we have more-precise, simple
      and reproducible density measures.

PMID- 22143146
TI  - Gynecological cancer: Home is where the fat is.

PMID- 22143147
TI  - Spectral and temporal reduction as stress cues in Dutch.
AB  - Although much has been written on the relative importance of acoustic correlates
      of linguistic stress for the listener, the role of spectral expansion/reduction
      has been much understudied. The present article is the first to study the role of
      spectral expansion/reduction in a two- parameter study together with temporal
      structure exploiting systematic variation of both parameters in a 7 * 7 stimulus
      space. We used a single minimal stress pair in Dutch, a language in which all
      classic acoustic correlates of stress were shown earlier to be relevant in single
      parameter studies, i.e. pitch movement, intensity (loudness), temporal
      organization and spectral expansion/reduction. The results of our study
      reconfirmed that temporal organization is a strong cue to stress perception when
      target words are presented out of focus (i.e. without a pitch accent on the
      target). Spectral expansion/reduction was a very weak stress cue; its effect was
      noticeable only when temporal structure was ambiguous between initial and final
      stress. These results suggest that spectral expansion/reduction is indeed the
      weakest of the four cues traditionally identified in the literature, at least in
      stress-accent languages such as English and Dutch.

PMID- 22143148
TI  - The phonetic manifestation of French /s#?/ and /?#s/ sequences in different vowel
      contexts: on the occurrence and the domain of sibilant assimilation.
AB  - While assimilation was initially regarded as a categorical replacement of
      phonemes or phonological features, subsequent detailed phonetic analyses showed
      that assimilation actually generates a wide spectrum of intermediate forms in
      terms of speech timing and spectrum. However, the focus of these analyses
      predominantly remained on the assimilated speech sound. In the present study we
      go one step ahead in two ways. First, we look at acoustic phonetic detail that
      differs in the French vowels /i, a, u/ preceding single /s/ and /?/ sibilants as
      well as /s#?/ and /?#s/ sibilant sequences. Second, our vowel measurements
      include not only F1 and F2 frequencies, but also traditional prosodic parameters
      like duration, intensity and voice quality. The vowels and sibilants were
      recorded as the central part of CVC#CVC pseudo-names in a contextualized read
      speech paradigm. In the single-sibilant conditions we found that the vowels
      preceding /?/ were longer, breathier, less intense, and had more cardinal F2
      values than before /s/. For the /s#?/ and /?#s/ conditions we found regressive
      and progressive /s/-to-[?] assimilation that was complete in terms of spectral
      centre-of-gravity measurements, although French is said to have only voice
      assimilation. Moreover, the vowels preceding the /s#?/ sequences still bear an
      imprint of /s/ despite the assimilation towards [ ??]. We discuss the
      implications of these findings for the time window and the completeness of
      assimilation as well as for the basic units in speech communication.

PMID- 22143149
TI  - Tone sandhi and tonal coarticulation in Tianjin Chinese.
AB  - We present in this article an acoustic study on tone sandhi and tonal
      coarticulation in Tianjin Chinese. Our results indicate that Tianjin tone sandhi
      is likely influenced by Standard Chinese and is undergoing a number of changes,
      causing variations and exceptions to the sandhi patterns, and the majority of the
      sandhis are non-neutralizing, contra traditional descriptions. Tonal
      coarticulation in Tianjin exhibits a number of well-known cross-linguistic
      properties: progressive assimilation, regressive dissimilation, a greater
      progressive effect, and a number of High/ Low asymmetries. Despite the
      dissimilatory properties observable from both tone sandhi and tonal
      coarticulation, they seem to have different characteristics, indicating different
      sources for the two processes.

PMID- 22143152
TI  - Wound healing and anti-inflammatory properties of Ranunculus pedatus and
      Ranunculus constantinapolitanus: a comparative study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In Turkish folk medicine Ranunculus species are
      used for wound healing and for the treatment of rheumatism. The present study was
      conducted to evaluate in vivo wound healing and anti-inflammatory properties of
      Ranunculus pedatus and Ranunculus constantinapolitanus. MATERIAL AND METHODS: In
      vivo wound healing activity of the extracts prepared from Ranunculus pedatus and
      Ranunculus constantinapolitanus was evaluated by linear incision and circular
      excision wound models. Hydroxyproline content of the treated tissues was also
      assessed. We also studied the anti-inflammatory activity using Whittle method
      with some modifications. RESULTS: Methanolic extract of Ranunculus pedatus showed
      significant wound healing effect both in incision (31.4%) and excision (55.74%)
      wound models. Methanolic extract of both Ranunculus pedatus and Ranunculus
      constantinapolitanus demonstrated anti-inflammatory activity with the inhibition
      value of 26.2% and 23.3% respectively, at the dose of 100 mg/kg. Hydroxyproline
      content of the tissues treated with the methanolic and aqueous extracts of
      Ranunculus pedatus and methanolic extract of Ranunculus constantinapolitanus were
      found to be significantly higher than that of the other extracts. CONCLUSION: The
      experimental data revealed that Ranunculus pedatus showed significant wound
      healing and anti-inflammatory effect.

PMID- 22143153
TI  - Cytoprotective effect of Coreopsis tinctoria extracts and flavonoids on tBHP and
      cytokine-induced cell injury in pancreatic MIN6 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Coreopsis tinctoria flowering tops
      infusion is traditionally used in Portugal for treating the symptoms of diabetes.
      Recent studies have revealed its antihyperglycemic activity when administered for
      3 weeks to a STZ-induced glucose intolerance model in the rat and glucose
      tolerance regain was even clearer and pancreatic function recovery was achieved
      when administering Coreopsis tinctoria flavonoid-rich AcOEt fraction. In this
      study we aimed to evaluate the protective effect of Coreopsis tinctoria flowering
      tops aqueous extract, AcOEt fraction and the pure compounds marein and
      flavanomarein, against beta-cell injury, in a mouse insulinoma cell line (MIN6)
      challenged with pro-oxidant tert-butyl-hydroperoxide (tBHP) or cytokines.
      MATERIALS AND METHODS: The protective effects of Coreopsis tinctoria flowering
      tops extracts and pure compounds were evaluated through pre-incubating MIN6 cells
      with samples followed by treatment with tBHP (400 MUM for 2 h) after which
      viability was determined through ATP measurements. In order to assess whether
      plant extracts were involved in decreasing reactive oxygen species, superoxide
      anion production was determined through a lucigenin-enhanced chemiluminescent
      method. Lastly, the direct influence of Coreopsis tinctoria extracts and main
      compounds on cell survival/apoptosis was determined measuring caspase 3 and 7
      cleavage induced by cytokines. RESULTS: Coreopsis tinctoria flowering tops
      extracts (25-100 MUg/mL) and pure compounds (200-400 MUM), when pre-incubated
      with MIN6 cells did not present any cytotoxicity, instead they increased cell
      viability in a dose dependent manner when challenged with tBHP. Treatment with
      this pro-oxidant also showed a rise in superoxide radical anion formation in MIN6
      cells. This increase was significantly reduced by treatment with superoxide
      dismutase enzyme (SOD) but not by pre-treatment with Coreopsis tinctoria
      flowering tops extracts. Caspase 3/7 activation measurements show that Coreopsis
      tinctoria flowering tops extracts, as well as marein and flavanomarein,
      significantly inhibit apoptosis. CONCLUSIONS: Coreopsis tinctoria extracts and
      pure compounds show cytoprotection that seems to be due to inhibition of the
      apoptotic pathway, and not through a decrease on superoxide radical production.

PMID- 22143154
TI  - In vitro antiplasmodial activity of indole alkaloids from the stem bark of
      Geissospermum vellosii.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Geissospermum vellosii has been
      traditionally used by the native population of northern South America to treat
      malaria. Indole alkaloids have been previously isolated from this plant, but the
      antiplasmodial constituents have not yet been described. As part of our ongoing
      investigations of new bioactive compounds with activity against malaria
      parasites, we tested the in vitro antiplasmodial activity of isolated fractions
      and purified alkaloids from Geissospermum vellosii. MATERIALS AND METHODS: Indole
      alkaloids were isolated and identified from a methanolic crude extract of
      Geissospermum vellosii bark using a combination of high performance counter
      current chromatography, mass spectrometry and nuclear magnetic resonance
      technologies. The methanolic extract, the crude alkaloid fractions and the
      purified compounds were tested for in vitro antiplasmodial activity against the
      chloroquine-sensitive strain of Plasmodium falciparum (D10). RESULTS: An indole
      alkaloid (4) along with four known indole alkaloids, geissolosimine (1),
      geissospermine (2), geissoschizoline (3), and vellosiminol (5) were isolated and
      structure elucidated. The antiplasmodial activity (IC(50)) of the methanolic
      crude extract was 2.22 MUg/mL, while for the isolated compounds it ranged from
      0.96 MUM to 13.96 MUM except for (5) which showed a low activity (157 MUM).
      Geissolosimine (1) showed the highest antiplasmodial activity (0.96 MUM).
      CONCLUSIONS: This study provides evidence to support the use of Geissospermum
      vellosii as an antimalarial agent, as used by the native populations.
      Geissolosimine (1) is a lead molecular structure for possible antimalarial drug
      development.

PMID- 22143155
TI  - The healing and anti-scar effects of astragaloside IV on the wound repair in
      vitro and in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Astragaloside IV is the chief ingredient of Radix
      Astragali, which has been used in the Traditional Chinese Medicine as a major
      component of many polyherbal formulations for the repair and regeneration of
      injured organ and tissues. This study is to investigate the influence of
      astragaloside IV on both of the wound healing and scar formation. MATERIALS AND
      METHODS: For the in vitro evaluation, the influence of the astragaloside IV in
      the wound scratch test of keratinocytes and the secretion of transforming growth
      factor-beta1, a key factor contributing to scar formation were determined. With
      the rat skin excision model, the in vivo regulation of astragaloside IV on wound
      closure, angiogenesis and collagen disposition were also evaluated. RESULTS:
      Astragaloside IV was shown to significantly promote the migration of
      keratinocytes in wound scratching assay. The superior effect of Astragaloside IV
      was observed at 100 MUmol/L, in which the recover rates was increased with 2 and
      3 folds after 48 h and 96 h respectively than that of blank control (P<0.01).
      Animal skin closure measurement showed that astragaloside IV could stimulate the
      wound healing, e.g. with 21% recover in contrast to the 8% of blank control at
      the 6th day. Biomechanic and Masson's trichrome stain analysis indicated that
      astragaloside IV may improve the strength of the repaired skin and promoted the
      angiogenesis and collagen synthesis. Meanwhile, the picrosirius-sirus red stain
      and Elisa test definitely showed the anti-scar effects of astragaloside IV by
      decreasing the levels of collagen I/III and TGF-beta1 secretion by firbroblasts
      with a dose-dependent manner (25-100 MUmol/L). CONCLUSIONS: Astragaloside IV was
      shown a promising natural product with both healing and anti-scar effects for
      wound treatment. These results give the evidence for the application of
      astragaloside IV in the treatment of injury.

PMID- 22143156
TI  - A new enneanuclear nickel(II) cluster with a rectangular face-centered trigonal
      prism structure and cluster glass behavior.
AB  - An enneanuclear nickel(II) complex with a rectangular face-centered trigonal
      prism structure bridged by MU(2)-pyrazolate, MU(6)-CO(3)(2-) and MU(3)-OH(-)
      groups was synthesized. It displays cluster glass-like magnetic behavior assigned
      to the single molecule magnet properties of {Ni(9)} clusters and weak
      intercluster interaction.

PMID- 22143157
TI  - Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome:
      current status.
AB  - Hematopoietic cell transplantation (HCT) offers potentially curative therapy for
      patients with myelodysplastic syndrome (MDS). However, as the majority of
      patients with MDS is in the 7th or 8th decade of life, only few of these patients
      were transplanted following high-dose conditioning regimens. The development of
      reduced-intensity conditioning has allowed to apply HCT also to older patients
      and those with clinically relevant comorbid conditions. Dependent upon disease
      status and the type of clonal chromosomal abnormalities present at the time of
      HCT, some 25-75% of patients will be cured of their disease and survive long
      term. Recent results with HLA-matched unrelated donors are comparable to those
      with HLA genotypically identical siblings. The increasing use of cord blood and
      HLA-haploidentical donors is expected to make HCT available to a growing number
      of patients. However, post-transplant relapse and graft-versus-host disease
      remain problems requiring further instigations.

PMID- 22143158
TI  - Molecular mechanisms and pathological consequences of endotoxin tolerance and
      priming.
AB  - Lipopolysaccharide (LPS), a component of Gram-negative bacteria, is a potent
      inflammatory stimulant, with high doses due to disseminated bacterial infection
      resulting in systemic inflammatory response syndrome and death. Lower doses can
      induce a state of tolerance to subsequent toxic doses of LPS, but extremely low
      doses have an opposite effect, priming the immune system for an even more violent
      response to subsequent challenge. A substantial body of research exists on the
      phenomenon of endotoxin tolerance, which appears to be a state of generalized
      dampening of inflammatory pathways. Comparatively little is known about the
      mechanisms or indeed the phenomenon of priming, particularly regarding the shift
      from a priming to a tolerizing response. Our aim is to review recent findings in
      the field of the inflammatory response to endotoxin, with a focus on highlighting
      the gaps in current understanding and attempting to reconcile the competing
      tolerance and priming phenomena.

PMID- 22143159
TI  - Neutrophil myeloperoxidase: soldier and statesman.
AB  - Myeloperoxidase (MPO) is a major protein constituent of the primary granules of
      vertebrate neutrophils. It catalyses the hydrogen peroxide-mediated oxidation of
      halide ions to hypohalous acids, especially HOCl. These reactive oxygen species
      can participate in a variety of secondary reactions, leading to modifications of
      amino acids and many types of biological macromolecules. The classic paradigm
      views MPO as a component of the phagocyte oxygen-dependent intracellular
      microbicidal system, and thus an important arm of the effector phase of innate
      immune responses. However, the limited immunodeficiency associated with lack of
      MPO in mouse and human models has challenged this paradigm. In this review we
      examine more recent information on the interaction between MPO, its bioreactive
      reaction products, and targets within the inflammatory microenvironment. We
      propose that two assumptions of the current model may require revisiting. First,
      many important targets of MPO modification are extracellular, rather than present
      only within the phagolysosome, such as various components of neutrophil
      extracellular traps. Second, we suggest that the pro-inflammatory pathological
      role of MPO may be a particular feature of chronic inflammation. In the
      physiological setting of acute neutrophil-mediated inflammation MPO may also form
      part of a negative feedback loop which down-regulates inflammation, limits tissue
      damage, and facilitates the switch from innate to adaptive immunity. This
      different perspective on this well-studied enzyme may usefully inform further
      research into its function in health and disease.

PMID- 22143160
TI  - Immunotherapy of lung adenocarcinoma patient with Peptide-pulsed dendritic cells:
      a case report.
AB  - Immunotherapy with ex vivo generated dendritic cells (DCs) is reported to be of
      low toxicity and of diverse effectiveness in cancer treatment. The synthetic
      antigens are frequently used for immunotherapy especially for patients with
      stable disease after prior treatment. We described the effect of peptide-loaded
      DCs-based immunotherapy on patient with recurrent surgically resected
      adenocarcinoma with bronchoalveolar feature with co-existing of Takayasu
      arteritis and chronic hepatitis B. In January 2010, 61-year-old patient received
      subcutaneously four bi-weekly vaccinations of DCs loaded with MUC1 and MAGE-3
      epitopes. Additionally, he received three bi-weekly booster vaccinations after 7
      months from the first course of immunotherapy. Delayed-type hypersensitivity test
      was positive only for MAGE-3 antigen. The evidence expansion of MAGE-3-specific
      CD8(+) cells after first vaccination and after third vaccination during boosters
      injections was observed (from 0.08% before vaccination to 0.5% after first
      vaccination; from 0.05% before booster vaccination to 0.24% after third
      injection). Computed tomography scans performed after first course and after
      booster course of vaccination until April 2011 did not shown any presence of lung
      tumour or metastases. Based on clinical factors (no completed wedge-resection and
      recurrent character of cancer) as well as on the presence of the tumour-antigen
      specific immunological response, we could speculated that immunotherapy prolonged
      disease free-survival in our patient. Over 16 months from first vaccination, the
      patient remains without symptoms of cancer.

PMID- 22143161
TI  - Orchiectomy attenuates kidney fibrosis after ureteral obstruction by reduction of
      oxidative stress in mice.
AB  - BACKGROUND/AIMS: Men are generally more prone to chronic kidney disease and
      progression to end-stage renal disease than women. However, the underlying
      mechanisms remain unclear. In this study, we investigated the role of reactive
      oxygen species and testosterone in the progression of renal fibrosis in mice with
      unilateral ureteral obstruction (UUO). METHODS: Mice were subjected to either
      orchiectomy or sham operation 14 days before either UUO or sham surgery.
      Harvesting of the kidney was performed 7 days after the UUO surgery to measure
      the production of reactive oxygen species and expression of antioxidants such as
      catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase,
      as well as fibrosis markers including alpha-smooth muscle actin (alpha-SMA) and
      collagen. RESULTS: UUO resulted in increased expression of alpha-SMA and collagen
      deposition in the kidneys of both female and male mice. These increases were
      significantly greater in males than females. Orchiectomy significantly reduced
      increases in alpha-SMA expression and collagen deposition when compared with
      intact male. UUO increased the production of hydrogen peroxide and lipid
      peroxidation along with the decreases in expression of manganese superoxide
      dismutase, copper-zinc superoxide dismutase, and catalase. These changes induced
      by UUO were significantly attenuated by orchiectomy. CONCLUSION: Males are more
      susceptible to UUO-induced kidney fibrosis compared with females, and the higher
      susceptibility of males is obviated by orchiectomy along with reduction in
      oxidative stress.

PMID- 22143162
TI  - Pharmacists' perceptions of participation in a community pharmacy-based nicotine
      replacement therapy distribution program.
AB  - The community pharmacy has been proposed as an ideal location for providing
      smoking cessation therapy to large numbers of patients. Studies of public health
      initiatives providing free nicotine replacement products through telephone
      quitlines have found increased call volumes and cessation rates. The purpose of
      this study was to evaluate a program where nicotine replacement therapy starter
      packs were provided to patients through community pharmacies at no cost. An
      online survey was developed to assess community pharmacists' participation in the
      program, perceptions of the initiative as a whole, and perceptions of smoking
      cessation counseling activities. Eighty-three pharmacists working at
      participating pharmacies completed the survey (65% response rate). Ninety-nine
      percent of pharmacists provided smoking cessation counseling during the study
      period; the median (IQR) number of patients counseled over the initial 3.5-months
      of the NRT distribution program was 50 (24-100), and the median number of minutes
      per counseling session was five (3-7). Most (89%) agreed smoking cessation
      counseling was accommodated into the pharmacy work-flow. A majority (85%) agreed
      the community pharmacy is an ideal location for distributing free NRT products
      and that the program should be replicated in other pharmacies (78%).
      Participating pharmacists viewed the program positively and perceived it to be
      effective in helping patients quit smoking. In conclusion, the community pharmacy
      is a viable location for implementation of community-based public health
      initiatives related to smoking cessation.

PMID- 22143163
TI  - University personnel's attitudes and behaviors toward the first tobacco-free
      campus policy in Tennessee.
AB  - In 1994, Tennessee, the third largest tobacco-producing state in the U.S.,
      preempted tobacco regulation. However, in 2005, higher educational institutions
      were exempted from this preemption and the 2007 Non-Smoker Protection Act
      required educational facilities to create smoke-free environment. To this date,
      while all higher educational institutions have some sort of smoke-free policy,
      East Tennessee State University is the only public institution with a tobacco
      free policy. We investigated attitudes and behaviors of the university personnel,
      the most stable segment of the population, toward the policy and compliance with
      it using an internet-based survey. All employees (2,318) were invited to
      participate in a survey; 58% responded. Bivariate analyses found 79% of the
      respondents favored the policy. Multiple variable logistic regression analyses
      found support for the policy was higher among females [OR = 3.14; 95% CI (1.68,
      5.86)], administrators/professionals [OR = 3.47; 95% CI (1.78, 6.74)], faculty
      [OR = 2.69; 95% CI (1.31, 5.53)] and those affiliated with the College of
      Medicine [OR = 4.14; 95% CI (1.45, 7.85)]. While only 67 employees (5.6% of
      sample) reported they have not complied with the policy, around 80.8% reported
      observing someone engaged in non-compliance. The high level of support for the
      policy suggests it should be promoted throughout the higher education system and
      nationwide. At the same time, in preemptive states, higher educational
      institutions should be targeted as venues for strong tobacco-free policies. The
      gap in compliance, however, implies in tobacco-friendly environments, a tobacco
      free campus policy with no reporting and enforcement mechanisms could lead to
      high levels of non-compliance.

PMID- 22143164
TI  - The severity of ischemia determines and predicts malignant brain edema in
      patients with large middle cerebral artery infarction.
AB  - BACKGROUND: In order to determine the impact of the severity of ischemia on
      malignant edema formation, we investigated various degrees of perfusional deficit
      by (11)C-flumazenil PET in patients with large middle cerebral artery (MCA)
      infarction. METHODS: 17 patients with large MCA stroke were included. Cerebral
      blood flow (CBF) was measured 15.9 +/- 6.4 h after the ictus. Patients were
      divided into a malignant (n = 9) and a benign group (n = 8) as a function of
      their clinical courses and edema. Edema was measured as maximal midline shift on
      follow-up CTs. Total hypoperfusion volume was divided into different subvolumes
      according to the degree of CBF reduction. RESULTS: Subvolumes of severe ischemia
      relative to total ischemic area were significantly larger in the malignant group
      than in the benign group and were significantly correlated with edema formation.
      The highest correlation and best predictive values for edema formation with a
      sensitivity, specificity, and a positive and negative predictive value of 100%
      were found for subvolumes with severe ischemia. Correlation coefficients and
      prediction decreased for subvolumes with less severe perfusional deficit,
      pointing to the risk of misclassifying patients when relying on the volume of
      total perfusional deficit alone. CONCLUSIONS: Malignant MCA infarction seems to
      be determined more by the volume of severe perfusional deficit than that of total
      perfusional deficit. Assessment of severely ischemic areas allows prediction of
      malignant edema formation and might help to select candidates for
      hemicraniectomy.

PMID- 22143165
TI  - A quantitative assay for insulin-expressing colony-forming progenitors.
AB  - The field of pancreatic stem and progenitor cell biology has been hampered by a
      lack of in vitro functional and quantitative assays that allow for the analysis
      of the single cell.  Analyses of single progenitors are of critical importance
      because they provide definitive ways to unequivocally demonstrate the lineage
      potential of individual progenitors. Although methods have been devised to
      generate "pancreatospheres" in suspension culture from single cells, several
      limitations exist. First, it is time-consuming to perform single cell deposition
      for a large number of cells, which in turn commands large volumes of culture
      media and space. Second, numeration of the resulting pancreatospheres is labor
      intensive, especially when the frequency of the pancreatosphere-initiating
      progenitors is low. Third, the pancreatosphere assay is not an efficient method
      to allow both the proliferation and differentiation of pancreatic progenitors in
      the same culture well, restricting the usefulness of the assay. To overcome these
      limitations, a semi-solid media based colony assay for pancreatic progenitors has
      been developed and is presented in this report. This method takes advantage of an
      existing concept from the hematopoietic colony assay, in which methylcellulose is
      used to provide viscosity  to the media, allowing the progenitor cells to stay in
      three-dimensional space as they undergo proliferation as well as differentiation.
      To enrich insulin-expressing colony-forming progenitors from a heterogeneous
      population, we utilized cells that express neurogenin (Ngn) 3, a pancreatic
      endocrine progenitor cell marker. Murine embryonic stem (ES) cell-derived Ngn3
      expressing cells tagged with the enhanced green fluorescent protein reporter were
      sorted and as many as 25,000 cells per well were plated into low-attachment 24
      well culture dishes.  Each well contained 500 MUL of semi-solid media with the
      following major components: methylcellulose, Matrigel, nicotinamide, exendin-4,
      activin betaB, and conditioned media collected from murine ES cell-derived
      pancreatic-like cells. After 8 to 12 days of culture, insulin-expressing colonies
      with distinctive morphology were formed and could be further analyzed for
      pancreatic gene expression using quantitative RT-PCR and immunoflourescent
      staining to determine the lineage composition of each colony. In summary, our
      colony assay allows easy detection and quantification of functional progenitors
      within a heterogeneous population of cells. In addition, the semi-solid media
      format allows uniform presentation of extracellular matrix components and growth
      factors to cells, enabling progenitors to proliferate and differentiate in vitro.
      This colony assay provides unique opportunities for mechanistic studies of
      pancreatic progenitor cells at the single cell level.

PMID- 22143166
TI  - Metal and metal oxide nanoparticle synthesis from metal organic frameworks
      (MOFs): finding the border of metal and metal oxides.
AB  - Herein, for the first time, we report a generalized strategy for the successful
      synthesis of highly crystalline metal and metal oxide nanoparticles embedded in a
      carbon matrix by the controlled thermolysis of metal organic frameworks (MOFs).
      The rationalized synthesis strategy of a broad range of metal and metal oxides
      nanoparticles, such as Cu/CuO, Co/Co(3)O(4), ZnO, Mn(2)O(3), MgO and CdS/CdO, by
      thermolysis of MOFs demonstrates for the first time that metal ions with a
      reduction potential of -0.27 volts or higher present in MOFs always form pure
      metal nanoparticles during thermolysis in N(2), whereas metal ions with a
      reduction potential lower than -0.27 volts form metal oxide nanoparticles during
      thermolysis in N(2). Another point of interest is the fact that we have found a
      unique relationship between the nanoparticle size and the distance between the
      secondary building units inside the MOF precursors. Interestingly, the
      crystallinity of the carbon matrix was also found to be greatly influenced by the
      environment (N(2) and air) during thermolysis. Moreover, these nanoparticles
      dispersed in a carbon matrix showed promising H(2) and CO(2) adsorption
      properties depending on the environment used for the thermolysis of MOFs.

PMID- 22143167
TI  - Effectiveness of plain radiography in diagnosing hollow viscus perforation: study
      of 1,723 patients of perforation peritonitis.
AB  - Gastrointestinal perforations remain the most common cause of surgical
      pneumoperitoneum since time immemorial. The aim of this study was to find out the
      effectiveness of plain radiography in diagnosing hollow viscous perforation. A
      prospective analysis of a total of 1,723 patients of perforation peritonitis
      between January 2009 and June 2011, confirmed by exploratory laparotomy, was
      worked out in the study. All these patients had undergone either an upright chest
      or erect abdominal or both radiographs before undergoing operative procedure.
      Pneumoperitoneum was evaluated, and the findings were compared with that of
      exploratory laparotomy. Out of the 1,723 patients of documented perforation on
      intraoperative finding, 1,537 patients showed pneumoperitoneum on preoperative
      plain radiography. The overall positivity rate of plain radiography in detecting
      pneumoperitoneum was 89.20%. The positivity rate was highest for stomach and
      duodenal perforation (94.19%) and the least for appendicular perforation (7.69%)
      with highly significant difference (p value, <0.001). In developing world, where
      there is limited availability of resources and overburden of patients, imposing a
      limitation in adapting advanced radiological technique as a first line of
      investigation, plain radiography may be considered as a valuable screening tool
      in detecting pneumoperitoneum with high positivity rate.

PMID- 22143169
TI  - Predictors of pain relieving response to sympathetic blockade in complex regional
      pain syndrome type 1.
AB  - BACKGROUND: Sympathetic blockade with local anesthetics is used frequently in the
      management of complex regional pain syndrome type 1(CRPS-1), with variable
      degrees of success in pain relief. The current study investigated which signs or
      symptoms of CRPS-1 could be predictive of outcome. The incidence of side effects
      and complications of sympathetic blockade also were determined prospectively.
      METHODS: A prospective observational study was done of 49 patients with CRPS-1 in
      one extremity only and for less than 1-yr duration who had severe pain and
      persistent functional impairment with no response to standard treatment with
      medication and physical therapy. RESULTS: Fifteen (31%) patients had good or
      moderate response. The response rate was not different in patient groups with
      cold or warm type CRPS-1 or in those with more or less than 1.5 degrees C
      differential increase in skin temperature after sympathetic blockade. Allodynia
      and hypoesthesia were negative predictors for treatment success in CRPS-1. There
      were no symptoms or signs of CRPS-1 that positively predicted treatment success.
      A majority of patients (84%) experienced transient side effects such as headache,
      dysphagia, increased pain, backache, nausea, blurred vision, groin pain,
      hoarseness, and hematoma at the puncture site. No major complications were
      reported. CONCLUSIONS: The presence of allodynia and hypoesthesia are negative
      predictors for treatment success. The selection of sympathetic blockade as
      treatment for CRPS-1 should be balanced carefully between potential success and
      side effect ratio. The procedure is as likely to cause a transient increase in
      pain as a decrease in pain. Patients should be informed accordingly.

PMID- 22143168
TI  - Dysautonomia: perioperative implications.
AB  - Severe autonomic failure occurs in approximately 1 in 1,000 people. Such patients
      are remarkable for the striking and sometimes paradoxic responses they manifest
      to a variety of physiologic and pharmacologic stimuli. Orthostatic hypotension is
      often the finding most commonly noted by physicians, but a myriad of additional
      and less understood findings also occur. These findings include supine
      hypertension, altered drug sensitivity, hyperresponsiveness of blood pressure to
      hypo/hyperventilation, sleep apnea, and other neurologic disturbances. In this
      article the authors will review the clinical pathophysiology that underlies
      autonomic failure, with a particular emphasis on those aspects most relevant to
      the care of such patients in the perioperative setting. Strategies used by
      clinicians in diagnosis and treatment of these patients, and the effect of these
      interventions on the preoperative, intraoperative, and postoperative care that
      these patients undergo is a crucial element in the optimized management of care
      in these patients.

PMID- 22143170
TI  - Prognostic value of real time dobutamine stress myocardial contrast
      echocardiography in patients with chest pain syndrome.
AB  - The aims of this study were (1) to evaluate the prognostic value of negative wall
      motion (WM) and myocardial perfusion during contrast-dobutamine stress
      echocardiography (DSE), (2) to determine whether WM-myocardial contrast
      echocardiography (MCE) had incremental prognostic value over just WM during DSE
      in patients with chest pain in the emergency room (ER), and (3) to compare the
      prognostic value of negative DSE-WM, and DSE-WM-MCE to nuclear-myocardial
      perfusion imaging (N-MPI) in a similar patient population over the same time
      period. We retrospectively studied 569 patients with real time contrast DSE, and
      147 patients underwent N-MPI for evaluation of chest pain. Follow-up for cardiac
      events was obtained between 12 and 25 months. The cumulative cardiac event-free
      survival was 94.5% in negative DSE-WM, 97.1% in negative DSE-WM-MCE and 96.7% in
      negative N-MPI group. Cardiac event-free survival of the negative DSE-WM-MCE
      group was significantly higher than the DSE-WM group (log rank P < 0.01), and
      similar in the DSE-WM-MCE group compared to the N-MPI group. Combined WM and
      perfusion during DSE was the strongest independent predictor for cardiac events.
      The negative predictive power of DSE-WM-MCE is superior to that of just negative
      DSE-WM and is comparable to that of N-MPI. Myocardial perfusion and WM analysis
      during DSE provide independent information for predicting cardiac events in
      patients with chest pain syndrome in the ER.

PMID- 22143171
TI  - Patterns of myocardial perfusion in humans evaluated with contrast-enhanced 320
      multidetector computed tomography.
AB  - Left ventricular (LV) myocardial contrast enhancement can be recorded using 320
      multi detector computed tomography (MDCT). We aimed to (1) assess patterns of
      regional myocardial perfusion at rest and compare them with NH(3) positron
      emission tomography (PET) (2) and to assess the effect of intravenous adenosine
      infusion on regional myocardial perfusion. To evaluate myocardial perfusion
      patterns at rest, we scanned 14 healthy subjects with PET and 14 age and gender
      matched subjects with 320 MDCT. To evaluate the effect of adenosine stress on
      relative perfusion patterns 14 subjects with near-normal epicardial coronary
      arteries were studied at rest and during adenosine stress. Relative perfusion was
      assessed as attenuation density (AD) in 16 segments of the LV, and each segment
      was divided into 3 layers: endo-, mid- and epi-cardial. During rest the relative
      AD by MDCT was lower in the lateral wall compared with the remainder of the LV (P
      < 0.002). A similar pattern was found by PET-imaging. LV endocardial AD was
      higher than mid- and epicardial AD (P < 0.05). At rest the endocardial/epicardial
      ratio in the septum was 0.99 compared with 1.23 in non-septal segments (P <
      0.001). During adenosine infusion transmural AD increased due to significant
      increases in the mid- and epicardium and the endocardial/epicardial ratio
      decreased by 18% in non-septal segments (from 1.23 to 1.05 P < 0.001). Relative
      perfusion at rest is lower in the lateral wall of the LV with both PET and MDCT
      compared to the remainder of the myocardium. During adenosine stress
      endocardial/epicardial ratio decrease significantly.

PMID- 22143172
TI  - Metagenomic cellulases highly tolerant towards the presence of ionic liquids-
      linking thermostability and halotolerance.
AB  - Cellulose is an important renewable resource for the production of bioethanol and
      other valuable compounds. Several ionic liquids (ILs) have been described to
      dissolve water-insoluble cellulose and/or wood. Therefore, ILs would provide a
      suitable reaction medium for the enzymatic hydrolysis of cellulose if cellulases
      were active and stable in the presence of high IL concentrations. For the
      discovery of novel bacterial enzymes with elevated stability in ILs, metagenomic
      libraries from three different hydrolytic communities (i.e. an enrichment culture
      inoculated with an extract of the shipworm Teredo navalis, a biogas plant sample
      and elephant faeces) were constructed and screened. Altogether, 14 cellulolytic
      clones were identified and subsequently assayed in the presence of six different
      ILs. The most promising enzymes, CelA2, CelA3 (both derived from the biogas
      plant) and CelA84 (derived from elephant faeces), showed high activities (up to
      6.4 U/mg) in the presence of 30% (v/v) ILs. As these enzymes were moderately
      thermophilic and halotolerant, they retained 40% to 80% relative activity after
      34 days in 4 M NaCl, and they were benchmarked with two thermostable enzymes,
      CelA from Thermotoga maritima and Cel5K from a metagenome library derived from
      Avachinsky crater in Kamchatka. These enzymes also exhibited high activity (up to
      11.1 U/mg) in aqueous IL solutions (30% (v/v)). Some of the enzymes furthermore
      exhibited remarkable stability in 60% (v/v) IL. After 4 days, CelA3 and Cel5K
      retained up to 79% and 100% of their activity, respectively. Altogether, the
      obtained data suggest that IL tolerance appears to correlate with thermophilicity
      and halotolerance.

PMID- 22143173
TI  - Public health challenges of electronic cigarettes in South Korea.
AB  - Electronic cigarettes (e-cigarrettes) were recently introduced and advertised as
      a smoking cession device in South Korea. As the social norm to quit smoking has
      gained hold in the country, the number of e-cigarette users is growing rapidly.
      This phenomenon should be urgently considered, because of the lack of research
      that has been conducted to examine the safety of e-cigarettes and its efficacy as
      a smoking cessation aid.  This paper raises several public health concerns on e
      cigarettes in South Korea. Uncertain regulations of the government on e
      cigarettes are contributing to an increase of e-cigarette users and allowing the
      e-cigarette industry to circumvent existing regulations. The aggressive marketing
      activity of this industry is also a core factor that is responsible for the rapid
      increase of e-cigarette use, in particular among the youth. Following the
      enforcement of tobacco control, some cigarette smokers may be encouraged to
      purchase e-cigarettes in order to circumvent the regulations, even though the
      dual use of e-cigarette and cigarette may be more harmful.  Until there is clear
      evidence of the e-cigarette's safety, it is recommended that the industry's
      marketing and promotional activities be banned and closely monitored, and public
      campaigns be initiated to educate the public regarding e-cigarettes.

PMID- 22143174
TI  - Deprivation and mortality at the town level in Busan, Korea: an ecological study.
AB  - OBJECTIVES: Busan is reported to have the highest mortality rate among 16
      provinces in Korea, as well as considerable health inequality across its
      districts. This study sought to examine overall and cause-specific mortality and
      deprivation at the town level in Busan, thereby identifying towns and causes of
      deaths to be targeted for improving overall health and alleviating health
      inequality. METHODS: Standardized mortality ratios (SMRs) for all-cause and four
      specific leading causes of death were calculated at the town level in Busan for
      the years 2005 through 2008. To construct a deprivation index, principal
      components and factor analysis were adopted, using 10% sample data from the 2005
      census. Geographic information system (GIS) mapping techniques were applied to
      compare spatial distributions between the deprivation index and SMRs. We fitted
      the Gaussian conditional autoregressive model (CAR) to estimate the relative
      risks of mortality by deprivation level, controlling for both the heterogeneity
      effect and spatial autocorrelation. RESULTS: The SMRs of towns in Busan averaged
      100.3, ranging from 70.7 to 139.8. In old inner cities and towns reclaimed for
      replaced households, the deprivation index and SMRs were relatively high. CAR
      modeling showed that gaps in SMRs for heart disease, cerebrovascular disease, and
      physical injury were particularly high. CONCLUSIONS: Our findings indicate that
      more deprived towns are likely to have higher mortality, in particular from
      cardiovascular disease and physical injury. To improve overall health status and
      address health inequality, such deprived towns should be targeted.

PMID- 22143175
TI  - Changes in contribution of causes of death to socioeconomic mortality
      inequalities in Korean adults.
AB  - OBJECTIVES: This study aimed to analyze long-term trends in the contribution of
      each cause of death to socioeconomic inequalities in all-cause mortality among
      Korean adults. METHODS: Data were collected from death certificates between 1990
      and 2004 and from censuses in 1990, 1995, and 2000. Age-standardized death rates
      by gender were produced according to education as the socioeconomic position
      indicator, and the slope index of inequality was calculated to evaluate the
      contribution of each cause of death to socioeconomic inequalities in all-cause
      mortality. RESULTS: Among adults aged 25-44, accidental injuries with transport
      accidents, suicide, liver disease and cerebrovascular disease made relatively
      large contributions to socioeconomic inequalities in all-cause mortality, while,
      among adults aged 45-64, liver disease, cerebrovascular disease, transport
      accidents, liver cancer, and lung cancer did so. Ischemic heart disease, a very
      important contributor to socioeconomic mortality inequality in North America and
      Western Europe, showed a very low contribution (less than 3%) in both genders of
      Koreans. CONCLUSIONS: Considering the contributions of different causes of death
      to absolute mortality inequalities, establishing effective strategies to reduce
      socioeconomic inequalities in mortality is warranted.

PMID- 22143176
TI  - Arterial stiffness is associated with diabetic retinopathy in Korean type 2
      diabetic patients.
AB  - OBJECTIVES: We evaluated the association between common carotid artery intima
      media thickness (CCA-IMT), brachial-ankle pulse wave velocity (baPWV), carotid
      plaque, and peripheral arterial disease (PAD) as indicators of macroangiopathy
      and diabetic retinopathy as an indicator of microangiopathy in type 2 diabetic
      patients. METHODS: We analyzed 605 type 2 diabetic patients registered at a
      public health center in Korea. Following overnight fasting, venous blood and
      urine samples were collected and analyzed. The CCA-IMT, levels of carotid plaque,
      baPWV, and ankle-brachial index (ABI) of the subjects were assessed. We used non
      mydriatic fundus photography to diagnose diabetic retinopathy. Multiple logistic
      regression analyses were used to evaluate the association between macroangiopathy
      and diabetic retinopathy. CCA-IMT and baPWV were divided into tertiles: CCA-IMT,
      0.39 to 0.65 mm, 0.66 to 0.78 mm, and 0.79 to 1.30 mm; baPWV, 9.9 to 15.8 m/s,
      15.9 to 18.9 m/s, and 19.0 to 38.0 m/s. RESULTS: The association between baPWV
      and diabetic retinopathy remained significant after adjustment, with an
      increasing odds ratio (OR) in the second tertile (OR, 2.41; 95% confidence
      interval [CI], 1.27 to 4.55) and the third tertile (OR, 4.63; 95% CI, 2.33 to
      9.21). No significant differences were observed in carotid plaque, PAD, and each
      tertile of CCA-IMT. CONCLUSIONS: BaPWV was associated with diabetic retinopathy,
      while CCA-IMT, carotid plaque, and PAD were not. This study suggests that the
      association between macroangiopathy and microangiopathy may be attributable to
      functional processes rather than structural processes within the vascular system.

PMID- 22143177
TI  - Disparities in health care utilization among urban homeless in South Korea: a
      cross-sectional study.
AB  - OBJECTIVES: We examined health care disparities in Korean urban homeless people
      and individual characteristics associated with the utilization of health care.
      METHODS: We selected a sample of 203 homeless individuals at streets, shelters,
      and drop-in centers in Seoul and Daejeon by a quota sampling method. We surveyed
      demographic information, information related to using health care, and health
      status with a questionnaire. Logistic regression analysis was adopted to identify
      factors associated with using health care and to reveal health care disparities
      within the Korean urban homeless population. RESULTS: Among 203 respondents, 89
      reported that they had visited health care providers at least once in the past 6
      months. Twenty persons (22.5%) in the group that used health care (n = 89)
      reported feeling discriminated against. After adjustment for age, sex, marital
      status, educational level, monthly income, perceived health status, Beck
      Depression Inventory score, homeless period, and other covariates, three factors
      were significantly associated with medical utilization: female sex (adjusted odds
      ratio [aOR, 15.95; 95% CI, 3.97 to 64.04], having three or more diseases (aOR,
      24.58; 95% CI, 4.23 to 142.78), and non-street residency (aOR, 11.39; 95% CI,
      3.58 to 36.24). CONCLUSIONS: Health care disparities in Seoul and Daejeon
      homeless exist in terms of the main place to stay, physical illnesses, and
      gender. Under the current homeless support system in South Korea, street homeless
      have poorer accessibility to health care versus non-street homeless. To provide
      equitable medical aid for homeless people, strategies to overcome barriers
      against health care for the street homeless are needed.

PMID- 22143178
TI  - Characterization of genomic imprinting effects and patterns with parametric
      accelerated failure time model.
AB  - Genomic imprinting, a genetic phenomenon of non-equivalent allele expression that
      depends on parental origins, has been ubiquitously observed in nature. It does
      not only control the traits of growth and development but also may be responsible
      for survival traits. Based on the accelerated failure time model, we construct a
      general parametric model for mapping the imprinted QTL (iQTL). Within the
      framework of interval mapping, maximum likelihood estimation of iQTL parameters
      is implemented via EM algorithm. The imprinting patterns of the detected iQTL are
      statistically tested according to a series of null hypotheses. BIC model
      selection criterion is employed to choose an optimal baseline hazard function
      with maximum likelihood and parsimonious parameters. Simulations are used to
      validate the proposed mapping procedure. A published dataset from a mouse model
      system was used to illustrate the proposed framework. Results show that among the
      five commonly used survival distributions, Log-logistic distribution is the
      optimal baseline hazard function for mapping QTL of hyperoxic acute lung injury
      (HALI) survival; under the log-logistic distribution, four QTLs were identified,
      in which only one QTL was inherited in Mendelian fashion, whereas others were
      imprinted in different imprinting patterns.

PMID- 22143179
TI  - Age-associated decrease of SIRT1 expression in rat hippocampus: prevention by
      late onset caloric restriction.
AB  - We have studied the effect of aging and late onset caloric restriction (CR) on
      the expression of SIRT1 in hippocampus and cerebral cortex of the rat.
      Quantitative analysis showed that there is a significant reduction of SIRT1
      protein levels in hippocampus with aging. Late onset, moderate CR prevented the
      deleterious effect of aging on SIRT1 content. Examination of SIRT1
      immunoreactivity in coronal sections from hippocampus supported these results,
      and confirmed that old animals are able to respond to the beneficial effects of
      CR by regulating SIRT1 protein expression. Differences in the amounts of SIRT1
      transcripts among animal groups were not found, which suggest that post
      transcriptional mechanisms could be involved in the effects of aging and CR on
      SIRT1 expression.

PMID- 22143180
TI  - Osteoporosis in 2011: Osteoporosis therapy--dawn of the post-bisphosphonate era.
AB  - Over the past decade, investigators have actively searched for safer therapeutic
      approaches to replace or complement the use of bisphosphonates and/or parathyroid
      hormone, exploring both antiresorptive and osteoanabolic pathways. Besides marked
      progress in basic research, the year 2011 has seen several compounds for the
      treatment of osteoporosis enter or progress within clinical trials.

PMID- 22143184
TI  - Diabetes: Intensive glucose control in type 1 diabetes mellitus reduces risk of
      GFR loss.

PMID- 22143186
TI  - Thyroid disease in pregnancy in 2011: Thyroid function--effects on mother and
      baby unraveled.
AB  - The complex relationship between pregnancy and thyroid function, and its clinical
      effect on mother and baby, continued to stimulate research in 2011. Key advances
      were made on three important issues: how long maternal thyroid function affects
      fetal thyroid hormone levels; whether thyroid autoimmunity affects pregnancy
      outcome; and the prevalence of permanent hypothyroidism after postpartum
      thyroiditis.

PMID- 22143188
TI  - Is surgery necessary for papillary thyroid microcarcinomas?

PMID- 22143190
TI  - Visual detection of lead(II) using a label-free DNA-based sensor and its
      immobilization within a monolithic hydrogel.
AB  - Lead is highly toxic and its detection has attracted a lot of research interests.
      In recent years, DNA has been used for Pb(2+) recognition and many fluorescent
      sensors with low to sub-nM detection limits have been reported. These figures of
      merit were typically measured using a spectrophotometer that can detect nM DNA
      with a high signal-to-noise ratio. For visual detection, however, MUM DNA or dye
      was required, making it difficult to detect low nM targets. We recently achieved
      a visual sensitivity of 10 nM Hg(2+) by immobilizing a DNA probe in a hydrogel.
      This was made possible because the gel was able to actively adsorb Hg(2+). In
      this work, we aim to test whether this method can be extended to the detection of
      Pb(2+). First, a new Pb(2+) sensor was designed based on a guanine-rich DNA and
      DNA binding dyes such as thiazole orange and SYBR Green I. The free DNA showed a
      detection limit of 8 nM Pb(2+) using 40 nM DNA. For visual detection in solution
      with 1 MUM of the DNA probe, however, ~300 nM Pb(2+) was required. After
      immobilization in a monolithic polyacrylamide hydrogel, even 20 nM Pb(2+) could
      be visually detected with a sample volume of 50 mL. Therefore, sensitive
      detection without signal amplification was achieved. Finally, we demonstrated
      simultaneous detection of both Hg(2+) and Pb(2+) in the same water sample with
      shape encoded hydrogel sensors.

PMID- 22143191
TI  - Impact of vascular calcification on corrected QT interval at the time of renal
      transplantation.
AB  - BACKGROUND/AIMS: Sudden death is the major cause of cardiac mortality in dialysis
      patients, accounting for approximately 60% of cardiovascular deaths. A prolonged
      QT interval and arterial calcification have been associated with increased
      cardiovascular morbidity and mortality in different patient populations including
      patients with chronic kidney disease (CKD). In the present study, we aimed to
      elucidate the association of vascular calcification with corrected QT interval
      duration in patients with end-stage renal disease. METHODS: We performed a single
      center cross-sectional study in patients referred for renal transplantation.
      Patients taking QT-prolonging agents or with conduction abnormalities were
      excluded. Aortic calcifications were scored by means of lumbar X-rays. RESULTS:
      In the final analysis, 193 patients (118 men, 52 years old) were included. A
      prolonged QT interval was observed in 26% of the patients. Multivariate analysis
      showed an independent and direct association between corrected QT duration and
      the extent of aortic calcifications (p = 0.0004) independent of age, gender,
      cardiovascular history, electrolytes and parameters of mineral metabolism.
      CONCLUSIONS: A prolonged QT interval is prevalent in patients with CKD stage 5D.
      Aortic calcification is associated with a prolonged QT duration, independent of
      traditional determinants.

PMID- 22143192
TI  - The public health scientist as informal logician.

PMID- 22143193
TI  - One-step hydrothermal synthesis of N-doped TiO2/C nanocomposites with high
      visible light photocatalytic activity.
AB  - N-doped TiO(2) nanoparticles modified with carbon (denoted N-TiO(2)/C) were
      successfully prepared by a facile one-pot hydrothermal treatment in the presence
      of L-lysine, which acts as a ligand to control the nanocrystal growth and as a
      source of nitrogen and carbon. As-prepared nanocomposites were characterized by
      thermogravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron
      microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), Raman
      spectroscopy, ultraviolet-visible (UV-vis) diffuse reflectance spectroscopy, X
      ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy
      (FTIR), electron paramagnetic resonance (EPR) spectra, and N(2) adsorption
      desorption analysis. The photocatalytic activities of the as-prepared
      photocatalysts were measured by the degradation of methyl orange (MO) under
      visible light irradiation at lambda>= 400 nm. The results show that N-TiO(2)/C
      nanocomposites increase absorption in the visible light region and exhibit a
      higher photocatalytic activity than pure TiO(2), commercial P25 and previously
      reported N-doped TiO(2) photocatalysts. We have demonstrated that the nitrogen
      was doped into the lattice and the carbon species were modified on the surface of
      the photocatalysts. N-doping narrows the band gap and C-modification enhances the
      visible light harvesting and accelerates the separation of the photo-generated
      electrons and holes. As a consequence, the photocatalytic activity is
      significantly improved. The molar ratio of L-lysine/TiCl(4) and the pH of the
      hydrothermal reaction solution are important factors affecting the photocatalytic
      activity of the N-TiO(2)/C; the optimum molar ratio of L-lysine/TiCl(4) is 8 and
      the optimum pH is ca. 4, at which the catalyst exhibits the highest reactivity.
      Our findings demonstrate that the as-obtained N-TiO(2)/C photocatalyst is a
      better and more promising candidate than well studied N-doped TiO(2) alternatives
      as visible light photocatalysts for potential applications in environmental
      purification.

PMID- 22143194
TI  - Imaging of estrogen receptor-alpha in rat pial arterioles using a digital
      immunofluorescent microscope.
AB  - Many of estrogen's effects on vascular reactivity are mediated through
      interaction with estrogen receptors (1, 2, 3). Although two sub-types exist
      (estrogen receptor -alpha and beta),estrogen receptor-alpha has been identified
      in both the smooth muscle and in endothelial cells of pial arterial segments
      using fluorescent staining combined with confocal laser scanning microscopy (4). 
      Furthermore, ER-alpha is located in the nuclei and in the cytoplasm of rat
      basilar arteries (5). The receptors are abundant and fluoresce brightly, but
      clear visualization of discrete groups of receptors is difficult likely due to
      the numbers located in many cell layers of pial vessel segments.  Additionally,
      many reports using immunohistochemical techniques paired with confocal microscopy
      poorly detail the requirements critical for reproduction of experiments (6). Our
      purpose for this article is to describe a simple technique to optimize the
      staining and visualization of ER-alpha using cross-sectional slices of pial
      arterioles obtain from female rat brains. We first perfuse rats with Evans blue
      dye to easily identify surface pial arteries which we isolate under a dissecting
      microscope.  Use of a cryostat to slice 8 MUm cross sections of the arteries
      allows us to obtain thin vessel sections so that different vessel planes are more
      clearly visualized.  Cutting across the vessel rather than use of a small vessel
      segment has the advantage of easier viewing of the endothelial and smooth muscle
      layers.  In addition, use of a digital immunofluorescent microscope with extended
      depth software produces clear images of ten to twelve different vessel planes and
      is less costly than use of a confocal laser scanning microscope.

PMID- 22143195
TI  - Admission CT perfusion is an independent predictor of hemorrhagic transformation
      in acute stroke with similar accuracy to DWI.
AB  - BACKGROUND: The utility of admission CT perfusion (CTP) to that of diffusion
      weighted imaging (DWI) as a predictor of hemorrhagic transformation (HT) in acute
      stroke was compared. METHODS: We analyzed the admission CTP and DWI scans of 96
      consecutive stroke patients. HT was present in 22 patients (23%). Infarct core
      was manually segmented on the admission DWI. We determined the: (1) hypoperfused
      tissue volume in the ischemic hemisphere using a range of thresholds applied to
      multiple different CTP parameter maps, and (2) mean relative CTP (rCTP) voxel
      values within both the DWI-segmented lesions and the thresholded CTP parameter
      maps. Receiver operating characteristic area under curve (AUC) analysis and
      multivariate regression were used to evaluate the test characteristics of each
      set of volumes and mean rCTP parameter values as predictors of HT. RESULTS: The
      hypoperfused tissue volumes with either relative cerebral blood flow (rCBF) <0.48
      (AUC = 0.73), or relative mean transit time (rMTT) >1.3 (AUC = 0.70), had similar
      accuracy to the DWI-segmented core volume (AUC = 0.68, p = 0.2 and p = 0.1,
      respectively) as predictors of HT. The mean rMTT voxel values within the rMTT
      >1.3 segmented lesion (AUC = 0.71) had similar accuracy to the mean rMTT voxel
      values (AUC = 0.65, p = 0.24) and mean rCBF voxel values (AUC = 0.64, p = 0.22)
      within the DWI-segmented lesion. The only independent predictors of HT were: (1)
      mean rMTT with rMTT >1.3, and (2) mechanical thrombectomy. CONCLUSION: Admission
      CTP-based hypoperfused tissue volumes and thresholded mean voxel values are
      markers of HT in acute stroke, with similar accuracy to DWI. This could be of
      value when MRI cannot be obtained.

PMID- 22143196
TI  - Development of an item bank and computer adaptive test for role functioning.
AB  - OBJECTIVES: Role functioning (RF) is a key component of health and well-being and
      an important outcome in health research. The aim of this study was to develop an
      item bank to measure impact of health on role functioning. METHODS: A set of
      different instruments including 75 newly developed items asking about the impact
      of health on role functioning was completed by 2,500 participants. Established
      item response theory methods were used to develop an item bank based on the
      generalized partial credit model. Comparison of group mean bank scores of
      participants with different self-reported general health status and chronic
      conditions was used to test the external validity of the bank. RESULTS: After
      excluding items that did not meet established requirements, the final item bank
      consisted of a total of 64 items covering three areas of role functioning
      (family, social, and occupational). Slopes in the bank ranged between .93 and
      4.37; the mean threshold range was -1.09 to -2.25. Item bank-based scores were
      significantly different for participants with and without chronic conditions and
      with different levels of self-reported general health. CONCLUSIONS: An item bank
      assessing health impact on RF across three content areas has been successfully
      developed. The bank can be used for development of short forms or computerized
      adaptive tests to be applied in the assessment of role functioning as one of the
      common denominators across applications of generic health assessment.

PMID- 22143197
TI  - Predictors of sustained return to work after work-related injury or disease:
      insights from workers' compensation claims records.
AB  - AIM: After work-related injury or disease, multiple spells of work absences and
      unsuccessful return to work (RTW) are common. The purpose of this study was to
      identify predictors of sustained RTW and work disability recurrences. METHODS:
      Australian WorkSafe Victoria claims containing income compensation payments
      starting between January 1st, 2001 and December 31st, 2004 (n = 59,526) were
      analysed over a 2-year observation window. Time until first RTW and final RTW,
      and 'recurrences' (cessations of payments of >7 days), were derived from claims
      payments data. Regression models were used relating demographic, occupational,
      workplace and injury characteristics to RTW outcomes. RESULTS: Although 94% of
      claimants had at least one RTW, only 79% achieved sustained RTW during follow-up.
      Median time until first RTW was 50 days; median time until final RTW was 91 days.
      Independent predictors of delayed final RTW were older age, afflictions involving
      the neck or multiple locations, and working in manufacturing. Of those who
      returned to work, 37% had at least one recurrence: risk factors were ages 35-55,
      female sex, working as a labourer, working in manufacturing, traumatic
      joint/ligament or muscle/tendon injury and musculoskeletal and connective tissue
      diseases, and afflictions involving the neck or multiple locations. CONCLUSIONS:
      Work disability recurrences are common and have considerable impact on sustained
      RTW outcomes. A policy focus on education about secondary prevention may help
      improve long-term RTW outcomes, particularly for persons with musculoskeletal
      disorders and those working in manufacturing.

PMID- 22143198
TI  - c-Jun induction is independent of early growth response factor during cerebellar
      granule neuron apoptosis.
AB  - Early growth response factor 1 (Egr-1) is induced during activity deprivation
      dependent apoptosis in cerebellar granule neurons and plays a critical role in
      neuronal apoptosis. It has been proposed that c-Jun lies downstream of the Egr
      dependent proapoptotic signaling cascade in cerebellar granule neurons. However,
      our data show that neither suppressing Egr activity using a dominant-negative
      mutant nor specifically silencing Egr-1 using small interfering RNA inhibited the
      activation and expression of c-Jun after activity deprivation in cerebellar
      granule neurons. Furthermore, two inhibitors, mithramycin A and chromomycin A3,
      which repressed transcription by selectively displacing GC-rich DNA-binding
      transcription factors (including those of the Egr family), did not attenuate the
      activation and expression of c-Jun during neuronal apoptosis. We conclude that c
      Jun induction is independent of Egr during apoptosis induced by activity
      deprivation in cerebellar granule neurons.

PMID- 22143199
TI  - Adaptation-induced plasticity and spike waveforms in cat visual cortex.
AB  - Orientation-selective neurons shift their preferred orientation after being
      adapted to a nonpreferred orientation. These shifts of the peaks of tuning curves
      may be in the attractive or repulsive direction in relation to the adapter
      orientation. In anesthetized cats, we recorded evoked electrical responses from
      the visual cortex in a conventional manner. The recorded spikes in cortex may
      present two typical waveforms: regular spikes or fast spikes. However, there is
      no evidence whether the shapes of spikes are related to the attractive or
      repulsive shifts of orientation tuning curves of cells. Our results show that
      after adaptation the recorded cells with both attractive and repulsive shifts
      display one or the other shape of spike. However, the magnitude of shifts is
      systematically higher for regular spikes, which is attributed to putative
      pyramidal cells, whereas tuning curves for fast spikes have smaller magnitudes
      and are evoked by putative interneurons.

PMID- 22143200
TI  - Polymorphism and spin crossover in mononuclear Fe(II) species containing new
      dipyridylamino-substituted s-triazine ligands.
AB  - Four new dipyridylamino-substituted s-triazine ligands DBB (N(2),N(2),N(4),N(4)
      tetrabenzyl-N(6),N(6)-di(pyridin-2-yl)-1,3,5-triazine-2,4,6-triamine), DDB
      (N(2),N(2),N(4),N(4)-tetrabutyl-N(6),N(6)-di(pyridin-2-yl)-1,3,5-triazine-2,4,6
      triamine), DCCl (6-chloro-N(2),N(2)-dicyclohexyl-N(4),N(4)-di(pyridin-2-yl)-1,3,5
      triazine-2,4-diamine) and DDT (N(2),N(2),N(4),N(4)-tetraphenyl-N(6),N(6)
      di(pyridin-2-yl)-1,3,5-triazine-2,4,6-triamine), have been incorporated into
      eight new, 0D Fe(II) compounds of type [Fe(II)(NCX)(2)(L)(2)].Solvent (where NCX
      = NCS(-), NCSe(-) or N(CN)(2)(-)). The polymorphic compounds alpha-trans
      [Fe(II)(NCS)(2)(DBB)(2)] (1) and beta-trans-[Fe(II)(NCS)(2)(DBB)(2)] (2) display,
      respectively, a relatively abrupt, complete, one-step spin transition with T(1/2)
      ~ 170 K, and a more gradual, complete, one-step spin transition with T(1/2) ~ 300
      K. Gradual, one-step spin transitions are observed for trans
      [Fe(II)(N(CN)(2))(2)(DBB)(2)].2CH(3)CH(2)OH (3) and trans
      [Fe(II)(NCSe)(2)(DCCl)(2)].2CH(3)OH (6) with T(1/2) ~ 280 K for both, while the
      one-step spin transition observed for a desolvated sample of trans
      [Fe(II)(NCSe)(2)(DDB)(2)].2CH(3)OH (4) is relatively abrupt, showing hysteresis
      with T(1/2?) = 285 K and T(1/2?) = 275 K. The compounds cis
      [Fe(II)(NCS)(2)(DDB)(2)] (5) and trans-[Fe(II)(NCS)(2)(DDT)(2)].4CH(2)Cl(2) (7)
      remain high spin, while structural data on trans
      [Fe(II)(NCSe)(2)(DDT)(2)].4CH(2)Cl(2) (8) suggests a spin transition at low
      temperatures. It is likely that distortion of the Fe(II)N(6) octahedron,
      intermolecular interactions and molecular conformation are crucial in deciding
      both the T(1/2) and abruptness of the spin transition for these species, although
      the nature of their influence varies. Variable temperature powder X-ray
      diffraction measurements on the polymorphs 1 and 2 reveal anisotropy in the unit
      cell parameters as the spin transition occurs.

PMID- 22143201
TI  - Stroke prevention in atrial fibrillation:  do we still need warfarin?
AB  - PURPOSE OF REVIEW: Oral anticoagulation with vitamin K antagonists (warfarin,
      phenprocoumon) is successful in both primary and secondary stroke prevention in
      patients with atrial fibrillation, yielding a 60-70% relative reduction in stroke
      risk compared with placebo, as well as a mortality reduction of 26%. However,
      these agents have a number of well documented shortcomings. Acetylsalicylic acid
      (ASA) reduces the relative risk of stroke by a nonsignificant 19% compared with
      placebo, and increased bleeding risk offsets any therapeutic gain from the
      combination of ASA with clopidogrel. This review describes the current landscape
      and developments in stroke prevention in patients with atrial fibrillation, with
      special reference to secondary prevention. RECENT FINDINGS: A number of new drugs
      for oral anticoagulation that do not exhibit the limitations of vitamin K
      antagonists are under investigation. These include direct factor Xa inhibitors
      and direct thrombin inhibitors. Recent studies (RE-LY, ROCKET-AF, AVERROES,
      ARISTOTLE) provide promising results for new agents, including higher efficacy
      and significantly lower incidences of intracranial bleeds compared with warfarin.
      The new substances show similar results in secondary as in primary stroke
      prevention in patients with atrial fibrillation. SUMMARY: New anticoagulants add
      to the therapeutic options for patients with atrial fibrillation, and offer a
      number of advantages over warfarin, for both the clinician and patient, including
      a favourable bleeding profile and convenience of use. Consideration of these new
      anticoagulants will improve clinical decision making.

PMID- 22143202
TI  - Current diagnosis and management of symptomatic intracranial atherosclerotic
      disease.
AB  - PURPOSE OF REVIEW: Intracranial atherosclerotic disease (IAD) is likely the most
      common cause of stroke world-wide and is associated with a very high risk of
      recurrence. It results in cerebral ischemia due to a variety of mechanisms,
      including artery-to-artery embolism, hemodynamic failure, and occlusion of
      penetrating arteries. New imaging modalities focused on physiological
      consequences of IAD have become available and recent treatment trials have been
      completed. RECENT FINDINGS: We review the traditional imaging modalities,
      emphasizing the advantages and limitations of each method, and discuss the novel
      physiological approaches that interrogate physiological process to indicate
      specific mechanisms of ischemia. These allow deeper understanding of the
      pathophysiological processes that underlie IAD-related ischemia. The key findings
      of recent therapeutic trials are reviewed, including the landmark randomized
      studies showing advantage of antiplatelet agents and risk factor modification,
      and a significant risk of complications with endovascular approaches. SUMMARY:
      Current evidence argues for aggressive medical management and suggests caution
      with interventional treatments. We propose that mechanistic information will
      further refine the risk assessment of patients with IAD to offer targeted
      therapy.

PMID- 22143203
TI  - A postoperative nomogram for local recurrence risk in extremity soft tissue
      sarcomas after limb-sparing surgery without adjuvant radiation.
AB  - PURPOSE: To develop a nomogram based on clinicopathologic factors to quantify the
      risk of local recurrence (LR) after limb-sparing surgery without adjuvant
      radiation (RT). METHODS: Review of our prospective sarcoma database identified
      684 patients with primary, nonmetastatic, extremity STS treated with limb-sparing
      surgery alone between June 1982 and December 2006. No patient received adjuvant
      radiation or chemotherapy. Age, sex, grade, depth, size, site, margin status and
      histology were analyzed for prognostic significance with respect to local
      recurrence rates using Gray's test. Variables which were significant in
      univariate analysis at the 0.05 level were entered into a multivariate competing
      risk regression model. On the basis of the multivariate analysis, a nomogram for
      predicting the 3- and 5-year risk of LR was developed using R libraries cmprsk
      and QHScrnomo. Concordance index (C-index) was calculated to evaluate the
      discriminatory power of the prognostic model. RESULTS: With a median follow-up of
      58 months for censored patients (73 months for all patients), the overall 3- and
      5-year actuarial local recurrence rates were 11% and 13%, respectively. Factors
      included in the nomogram were age (<= 50 vs. >50), size (<= 5 vs. >5 cm), margin
      status (negative vs. positive), grade (low vs. high), and histology (atypical
      lipomatous tumor/well differentiated liposarcoma vs. other). The STS nomogram
      predicted the local recurrence rate with a C-index of 0.73. CONCLUSIONS: A
      nomogram for extremity STS that includes age, size, margin status, grade of
      tumor, and histology predicts the 3- and 5-year risk of local recurrence after
      limb-sparing surgery in the absence of adjuvant RT.

PMID- 22143204
TI  - Impact of lymphadenectomy on the oncologic outcome of patients with
      adrenocortical carcinoma.
AB  - OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy with an
      unfavorable prognosis. The impact of a locoregional lymph node dissection (LND)
      has never been defined in this disease. We report the disease-specific outcome of
      patients treated with or without LND during primary adrenalectomy. METHODS: The
      medical records of patients followed by the German ACC Registry were
      retrospectively reviewed. Patients with incomplete resection or distant
      metastases were excluded. Only if the histologic analysis retrieved 5 or more
      lymph nodes, an intended LND was assumed (LND group). The predefined primary end
      point of the study was disease-specific survival. RESULTS: Of 283 included
      patients, 47 patients (16.6%) were treated with LND, whereas 236 patients (83.4%)
      underwent surgery without LND. Patients who underwent LND had a larger median
      tumor size (12.0 cm, range: 2.3-30 cm vs 10.0 cm, range: 4.0-39 cm, P = 0.007)
      and were more often treated by multivisceral resection (LND: 47.8% vs no-LND:
      18.1%; P < 0.001). The other baseline characteristics (age, sex, endocrine
      activity, Weiss score, Ki-67 index, and adjuvant treatment) did not differ
      significantly. Median follow-up of all patients still alive was 40 months (range:
      6-326). Multivariate analysis adjusted for age, tumor stage, multivisceral
      resection, adjuvant treatment, and lymph nodes status on preoperative imaging
      demonstrated a significantly reduced risk for tumor recurrence (hazard ratio:
      0.65; 95% confidence interval: 0.43-0.98; P = 0.042) and for disease-related
      death (hazard ratio: 0.54; 95% confidence interval: 0.29-0.99; P = 0.049) in LND
      patients when compared with no-LND patients. CONCLUSIONS: Our retrospective data
      indicate that locoregional LND improves tumor staging and leads to a favorable
      oncologic outcome in patients with localized ACC.

PMID- 22143205
TI  - In-transit intramammary sentinel lymph nodes from malignant melanoma of the
      trunk.
AB  - OBJECTIVE: Our goal was to determine the incidence and outcomes of intramammary
      in-transit sentinel lymph nodes (IMSLN) from primary malignant melanoma (MM) of
      the trunk. We hypothesize that regional metastasis to the breast from anterior
      trunk MM also occurs via the lymphatic system to these intramammary in-transit
      sentinel lymph nodes. BACKGROUND: MM is the most common solid tumor metastasis to
      the breast. The mechanism of intramammary (IM) metastasis is generally attributed
      to hematogenous rather than lymphatic spread. METHODS: We retrospectively
      reviewed medical records from all patients who underwent selective sentinel lymph
      node dissection at the UCSF Melanoma Center from 1993 to 2008 after the approval
      of UCSF Committee on Human Research. Of the 1911 cases, we found 614 patients
      with primary MM located on the trunk, and queried their medical records for in
      transit SLN and SLNs in the breast. Data from preoperative lymphoscintigraphy,
      intraoperative lymphatic mapping, operative notes, and pathology and clinic notes
      were gathered. RESULTS: Of the 1911 patients with MM, 169 (8.9%) and 420 (22.0%)
      had anterior and posterior trunk lesions, respectively, and 25 patients (1.3%)
      with flank lesions (lateral abdominal wall below the rib cage, above the iliac
      crest). Of the anterior trunk population, 18 patients had in-transit SLNs. The
      vast majority of these patients (14 of 18, 77.8%) had in-transit IMSLN. Of
      patients with posterior trunk melanoma, 27 patients had in-transit nodes with 1
      patient having IMSLNs. Of patients with flank melanomas, 3 patients had in
      transit nodes with 1 patient having IMSLNs. Interestingly, all patients with
      IMSLNs had primary lesions located inferior to the breasts. Two of the 16
      patients with IMSLNs had micrometastasis to IMSLN; 1 patient died and the other
      currently is disease free 4 years after initial SLND. Four of the 32 patients
      with non-IM in-transit nodes had micrometastases to these in-transit nodes. Of
      all patients with trunk melanomas, 4 patients had micrometastases to axillary
      SLNs (AxSLNs). Three of the 4 patients with positive AxSLNs also had positive in
      transit nodes whereas only half of the patients with positive in-transit SLNs had
      positive AxSLNs. CONCLUSIONS: IMSLNs exist in the breast. Our results establish
      an anatomic basis for lymphatic metastasis to the breast from primary cutaneous
      melanoma mainly from the anterior trunk inferior to the breasts. For anterior
      trunk melanomas, IMSLNs should not be overlooked during SLND as they may harbor
      micrometastasis.

PMID- 22143206
TI  - Development and validation of a novel stratification tool for identifying cancer
      patients at increased risk of surgical site infection.
AB  - OBJECTIVE: To identify cancer-specific predictors of postoperative surgical site
      infection (SSI), and to develop a risk-stratification prognostic tool and compare
      its performance with traditional measures. BACKGROUND: The incidence and risk
      factors for SSI in cancer patients are unknown; current risk-stratification tools
      are not cancer-specific. METHODS: A prospective cohort study of patients
      undergoing elective operations (n = 503) at a tertiary cancer center was
      conducted. SSI was assessed using postdischarge active surveillance. Multivariate
      logistic regression analyses were performed to identify predictors of SSI, and
      beta-coefficients were used to create a scoring system. The sum of these was used
      to create a Risk of Surgical Site Infection in Cancer (RSSIC) score. The RSSIC
      was validated using bootstrapping techniques, and its discrimination was compared
      with the National Nosocomial Infection Surveillance (NNIS) risk index. RESULTS:
      The 30-day SSI incidence was 24%. Significant predictors of SSI included
      preoperative chemotherapy (OR = 1.94 [95% CI, 1.16-3.25]), clean-contaminated
      wounds (OR = 2.1 [95% CI, 1.24-3.55]), operative time >=2 hours (OR = 1.75 [95%
      CI, 1.01-3.04]) and >=4 hours (OR = 2.24 [95% CI, 1.22-4.1]), and surgical site:
      groin (OR = 4.65 [95% CI, 1.69-12.83]), and head/neck (OR = 0.12 [95% CI, 0.02
      0.89]). The RSSIC score stratified patients into 4 risk strata for SSI. The
      performance of this score exceeded that of the NNIS score (AUC = 0.70 vs. 0.63,
      respectively; P = 0.01). CONCLUSION: SSIs are common following cancer surgery.
      Preoperative chemotherapy, in addition to other common risk factors, was
      identified as a significant predictor for SSI in cancer patients. The RSSIC
      improves risk-stratification of cancer patients and identifies those that may
      benefit from more aggressive or novel preventive strategies.

PMID- 22143207
TI  - [Nurses' experience of career ladder programs in a general hospital].
AB  - PURPOSE: The purpose of this study was to identify and describe nurses'
      experience of a career ladder program (CLP) in a general hospital in Korea.
      METHODS: The data were collected from 15 nurses who participated in the CLP. Each
      nurse completed individual in-depth interviews, for which the main interview
      question was "How do you describe your experience of CLP?". All interview data
      were transcribed and were analyzed using the grounded theory method. RESULTS: The
      core category of the experience of CLP was identified as "challenging to rebirth
      as an expert". The participants used five action/interaction strategies such as
      "taking some time for introspection", "appreciating the essence of nursing",
      "making use of feedback positively", "throwing away doubts about their own
      capabilities", "exerting themselves with confidence". The consequence of the
      process of adjusting to CLP was "positioning a differentiated expert."
      CONCLUSION: The results of this study show that participants recognized CLP as a
      powerful resource which leads them to professional growth and development. Thus,
      CLP could be utilized as a clinical career-promoting program and ultimately as a
      program for providing high-quality nursing services.

PMID- 22143208
TI  - [Maternal and hospital factors impacting the utilization of rooming-in care in
      South Korea: secondary analysis of national health data].
AB  - PURPOSE: In this study analysis was done of utilization of rooming-in care in
      South Korean hospitals in order to examine the factors related to mothers and
      hospitals that affect rooming-in care. METHODS: With the involvement of 254,414
      mothers who gave birth across 953 hospitals, the analysis used the health
      insurance qualification data of the National Health Insurance Corporations and
      Health Insurance Review and Assessment Service (2006). Factors associated with
      rooming-in care were analyzed using a GEE logistic regression analysis to
      consider factors related to both mothers and hospitals. RESULTS: Only 45.1% of
      the mothers used rooming-in care. The results of the regression analysis revealed
      that individual factors of the mothers were not associated with rooming-in care,
      whereas group factors of the hospitals were. Rooming-in care use was primarily
      related to small hospital, location of hospital, and higher nurse staffing level.
      CONCLUSION: The findings of this study indicate that the utilization of rooming
      in care is not associated with factors an individual mother, but rather with the
      group factors of the hospitals. Thus, a policy-based approach considering both of
      these types of factors is required to enhance the utilization of rooming-in care.

PMID- 22143209
TI  - [Illness experience of adolescents with hematologic malignancies].
AB  - PURPOSE: The purpose of this study was to describe the experience process of
      adolescents with hematologic malignancies. The question for the study was "What
      is the experience of adolescents with hematologic malignancies like?". METHODS:
      The grounded theory methodology was used for this study. The data were collected
      through in-depth interview from 10 adolescents with hematologic malignancies.
      Data collection was done from January to June 2007. Theoretical sampling was used
      until the data reached saturation. RESULTS: As a result of the analysis,
      "Reconstructing self-image from deviated and suspended life" was identified as
      the core category. And 11 subcategories were identified and they were integrated
      to the core category. 'Establishment of expanded and matured self' was identified
      as the consequence. CONCLUSION: The results of the study provide a frame for
      effective individualized nursing intervention strategies in helping adjustment of
      the adolescents with hematologic malignancies.

PMID- 22143210
TI  - [Growth patterns of premature infants up to 40th term week of corrected age].
AB  - PURPOSE: Study purpose were to describe growth patterns of premature infants in
      weight, length and head circumference from birth to 40th week of corrected ages
      (CA) and to explore factors affecting patterns. METHODS: A longitudinal
      descriptive study was conducted with 267 premature infants. They were categorized
      into 2 groups; GA group with measurements at birth and the CA group with
      measurements at CA, which was categorized into 3 groups (group 1-3) by WHO
      guideline for gestational age (GA) at birth. RESULTS: GA group presented greater
      measures in all than CA group at same week of life. Among CA groups, group 3
      showed the highest measurements, up to 37 weeks of life, though this disappeared
      at 38-40 weeks. Reversely, group 1 revealed the highest growth rates in all
      measures, followed by group 2 and group 3. Significant interaction was observed
      in all measures between week of life and any type of groups. CONCLUSION: Higher
      measures in GA group, as well group 3 among CA groups, supported the superiority
      of intra-uterine environment overriding quality of regimen from NICU. Regardless
      of growth acceleration, smaller infants remain smaller, indicating that intra
      uterine thrifty phenotype may continue at least up to the 40th week of CA.

PMID- 22143211
TI  - [A social network analysis of research topics in Korean nursing science].
AB  - PURPOSE: This study was done to explore the knowledge structure of Korean Nursing
      Science. METHODS: The main variables were key words from the research papers that
      were presented in the Journal of Korean Academy of Nursing and journals of the
      seven branches of the Korean Academy of Nursing. English titles and abstracts of
      the papers (n=5,936) published from 1995 through 2009 were included. Noun phrases
      were extracted from the corpora using an in-house program (BiKE Text Analyzer),
      and their co-occurrence networks were generated via a cosine similarity measure,
      and then the networks were analyzed and visualized using Pajek, a Social Network
      Analysis program. RESULTS: With the hub and authority measures, the most
      important research topics in Korean Nursing Science were identified. Newly
      emerging topics by three-year period units were observed as research trends.
      CONCLUSION: This study provides a systematic overview on the knowledge structure
      of Korean Nursing Science. The Social Network Analysis for this study will be
      useful for identifying the knowledge structure in Nursing Science.

PMID- 22143212
TI  - [A predictive model on turnover intention of nurses in Korea].
AB  - PURPOSE: The purpose of this study was to propose and test a predictive model
      that could explain and predict Korean nurses' turnover intentions. METHODS: A
      survey using a structured questionnaire was conducted with 445 nurses in Korea.
      Six instruments were used in this model. The data were analyzed using SPSS 15.0
      and Amos 7.0 program. RESULTS: Based on the constructed model, organizational
      commitment, and burnout were found to have a significant direct effect on
      turnover intention of nurses. In addition, factors such as empowerment, job
      satisfaction, and organizational commitment were found to indirectly affect
      turnover intention of nurse. The final modified model yielded chi2=402.30,
      p<.001), chi2/df=2.94, RMSEA=0.07, RMR=0.03, GFI=0.90, AGF=0.87, NFI=0.88,
      CFI=0.92 and good fit indices. CONCLUSION: This structural equational model is a
      comprehensive theoretical model that explains the related factors and their
      relationship with turnover intention in Korean nurses. Findings from this study
      can be used to design appropriate strategies to further decrease the nurses'
      turnover intention in Korea.

PMID- 22143213
TI  - [Factors influencing resilience of adult children of alcoholics among college
      students].
AB  - PURPOSE: The purpose of this study was to explore the resilience of adult
      children of alcoholics (ACOA) who are college students, and examine factors
      contributing to their resilience. METHODS: A total of 459 college students from a
      university in Incheon, participated in this study. Data were collected between
      April 6 to 30, 2010 using the Korean version of the Children of Alcoholics
      Screening Test (CAST-K), CAGE, Social Support, Self-Esteem, Family Adaptability
      and Cohesion, and Resilience measurements. Data were analyzed using the SPSS/WIN
      18.0 program. RESULTS: Overall, ACOA group showed lower scores of resilience,
      social support, self-esteem and family adaptability and cohesion compared to non
      ACOA group. Resilience among the ACOA group showed significant relationships with
      self-esteem (r=.53, p<.001), social support (r=.43, p<.001), and family
      adaptability and cohesion (r=.25, p<.013). Multiple regression analysis showed
      that 45% of the variance for resilience in the ACOA group was accounted for by
      age, gender, social support, self-esteem, and religion. CONCLUSION: The results
      of the study show that self-esteem and social support are important determinants
      of resilience in ACOA, thus it is recommend that further resilience training
      programs for ACOA be developed to enhance their social support and self-esteem,
      and ultimately to increase their resilience.

PMID- 22143214
TI  - [Factors on the suicidal attempt by gender of middle and high school student].
AB  - PURPOSE: The suicide rate of adolescents in Korea is increasing annually.
      Therefore, this research was done to identify the suicide attempt rate of middle
      and high school students and to identify factors that influence suicidal
      attempts. METHODS: The Korea Youth Health Risk Behavior Web-based Survey (2007)
      was used as data. Discriminant analysis and logistic regression were performed to
      analyze the data depending on gender to consider the gender difference in
      assessing the influence of each independent variable on suicidal attempts.
      RESULTS: Discriminant analysis according on gender showed that 13 factors
      correlated with suicidal attempts for boys, and 20 factors for girls. The most
      highly correlated factors were smoking, depression and inhalation experience. For
      inhalation experience, boys had 2.7 times higher possibility of suicide attempts
      (95% CI 1.8-3.0) and girls, a 2.4 times higher possibility (95% CI 1.7-3.5).
      CONCLUSION: The results of the study indicate a need to classify adolescents for
      expectation of suicide risk and high danger for suicidal attempts through, and
      introduce suicide prevention programs for these adolescents. In particular, it is
      necessary to start intervention with students who smoke, have sexual and
      inhalation experiences and high levels of depression.

PMID- 22143215
TI  - [Depression status of academic high school students in Seoul: mediating role of
      entrapment].
AB  - PURPOSE: Purpose of this study was to investigate the status of depression in
      academic high school students and path analysis model for exploring the mediating
      role of entrapment to depression in relation to academic stress and perceived
      social support. METHODS: Measurements were four reliable questionnaires measuring
      academic stress, social support, entrapment, and depression. Data were collected
      from students in 17 high schools in Seoul. RESULTS: Students (n=5,346) completing
      the questionnaires indicated depression & entrapment from academic stress.
      Depression was more prevalent in girls, those whose parents' household income was
      less than two million won, who did not live with father or mother or both due to
      divorce, separation, or death, and those who smoked or used alcohol. Entrapment
      was more prevalent in students similar to cases of depression and in seniors.
      According to the proposed path model, 48.6% of depression was explained by
      academic stress, social support, and entrapment. The indirect effect of
      entrapment as a mediator between academic stress and depression was verified and
      larger than the direct effect of academic stress on depression. CONCLUSION:
      Considering levels of depression and entrapment demonstrated by these students,
      better mental health programs with diverse strategies should be developed for
      their psychological well-being.

PMID- 22143216
TI  - [Development and effectiveness of a spiritual care education program for nursing
      students--based on the ASSET model].
AB  - PURPOSE: This study was done to develop a spiritual care education program (SCEP)
      for nursing students to help increase their awareness of the essence of
      spirituality in care so as to enable them to promote spiritual well-being and
      spiritual care competence. METHODS: The participants were assigned to an
      experimental group (n=42) or a control group (n=39). From August to October 2009,
      the experimental group participated in the SCEP, which were held 2 hours a week
      for 6 weeks. The data were analyzed using chi2-test, Fisher's exact probability
      test, paired t-test, t-test with the SPSS WIN 17.0 statistics program. RESULTS:
      The experimental group had a higher mean score for spirituality, spiritual well
      being and spiritual care competence than the control group. Significant
      differences were found between the experimental group and the control group.
      CONCLUSION: The results of this study indicate that the SCEP was effective in
      improving spirituality, spiritual well-being and spiritual care competence for
      nursing students.

PMID- 22143217
TI  - [The effects of oral care education on caregivers' knowledge, attitude, &
      behavior toward oral hygiene for elderly residents in a nursing home].
AB  - PURPOSE: To investigate the effects of oral care education on knowledge,
      attitudes & behavior of caregivers in oral care and oral hygiene for residents in
      nursing homes. METHODS: In this quasi-experimental study, the intervention group
      (n=27) of residents received oral care from intervention group caregivers (n=28)
      who had received 6 weeks of oral care education. The control group (n=27) of
      residents received usual oral care from control group caregivers (n=26). Data on
      knowledge, attitude, and behavioral change in oral health care by the caregivers
      and plaque index & halitosis of the residents were collected. Data were analyzed
      using SPSS WIN 16.0. RESULTS: 1) Scores on caregivers' knowledge (p<.001) and
      behavior (p<.001) for oral care were higher in the intervention group 6 and 12
      weeks. The caregivers' attitude (p<.001) score for oral care was higher in the
      intervention group 12 weeks. 2) The plaque index (p=.004) and halitosis (p=.002)
      of the nursing home residents were lower in the intervention group than the
      control group at 6 and 12 weeks. CONCLUSION: Oral care education programs for
      caregivers are effective in improving the oral hygiene of elderly residents in
      nursing homes through enhancement of caregivers' knowledge, attitude, and
      behavioral change.

PMID- 22143218
TI  - [Effects of a group counseling integration program on self-determination and
      Internet addiction in high school students with tendency to Internet addiction].
AB  - PURPOSE: In this study the effects of a Group Counseling Integration Program for
      students with a tendency to Internet addiction were examined. METHODS: Thirty
      seven students who were in a vocational high school in G city participated in a
      survey, which was carried out from October 12 to November 12, 2009. To test the
      effects of the Group Counseling Integration Program, the participants were
      divided into two groups, an experimental group (18) and a control group (19). The
      research design used in this study was a nonequivalent control group non
      synchronized pre-posttest quasi-experimental research design. The research tools
      included a self-determination scale and an internet addiction scale. Data were
      analyzed using Chi-square test, t-test, and ANCOVA with the SPSS/WIN 14.0
      program. RESULTS: Significant differences were found in self-determination scores
      and internet addiction scores between the experimental group and the control
      group (F=5.99, p=.020) (t=-2.53, p=.016). CONCLUSION: The results indicate that
      Group Counseling Integration Programs are an effective nursing intervention for
      improving self-determination and decreasing Internet addiction in students with a
      tendency to Internet addiction.

PMID- 22143219
TI  - [A systematic review of psychological distress as a risk factor for recurrent
      cardiac events in patients with coronary artery disease].
AB  - PURPOSE: The purpose of this study was to determine whether psychological
      distress is an independent risk factor for recurrent cardiac events in patients
      with coronary artery disease (CAD). METHODS: A prospective cohort of studies that
      measured psychological distress and the incidence of recurrent cardiac events in
      the adult population were included. Three computerized databases were assessed
      (PubMed, CINAHL, and PSYCINFO). Meta-analysis was conducted using a random
      effects model to determine summary estimates of risks of major recurrent cardiac
      events associated with each psychological distress. Of 506 publications
      identified, 33 met inclusion criteria, and 24 studies were used to estimate
      effect size of psychological distress on recurrent cardiac events. RESULTS: Mean
      number in the research sample was 736 and mean time of follow-up was 4.0 years.
      Depression, anxiety, anger, and hostility as psychological factors were studied.
      According to estimation of effect size using random model effect, depression
      (OR=1.39, 95% CI: 1.22-1.57), anxiety (OR=1.22, 95% CI: 0.96-1.56), and
      anger/hostility (OR=1.29, 95% CI: 1.07-1.57) CAD patients in significantly
      increased risk for recurrent cardiac events. CONCLUSION: Finding suggests that
      psychological distress in forms of depression, anxiety, anger, and hostility
      impact unfavorably on recurrent cardiac events in CAD patients.

PMID- 22143220
TI  - [Effects of human papillomavirus vaccination education on college women's
      knowledge, health belief, and preventive behavior intention].
AB  - PURPOSE: This study was done to evaluated the effects of Human Papillomavirus
      (HPV) vaccination education on college women's knowledge of HPV, health beliefs
      (perceived severity and perceived susceptibility), and preventive behavior
      intention. METHODS: A nonequivalent control group pretest-posttest design with
      repeated measures was used. Participants were 125 female college students in one
      university, assigned to an experimental group (72 students) and control group (53
      students). RESULTS: Two weeks after the intervention, the experimental group
      reported higher scores of knowledge, perceived severity, perceived
      susceptibility, and preventive behavior intention than the control group. All
      follow-up scores except intention measured at 5 weeks after the intervention from
      the experimental group remained still higher than those from the control group.
      CONCLUSION: The results suggest that the variable of preventive behavior
      intention which is believed to be the closest predictor of real vaccination rate
      could be affected by the education, but did not remain at the same level at 5
      weeks. Therefore, additional interventions may need to be provided before the
      educational effect on preventive behavior intention is greatly diminished.

PMID- 22143221
TI  - [Effects of Web-based health education on blood glucose and blood pressure
      improvement in postmenopausal women with impaired fasting blood glucose].
AB  - PURPOSE: The purpose of this study was to investigate the effectiveness of an
      educational intervention that used both cellular phones and the Internet to
      provide a short messaging service (SMS) relating to blood glucose, blood
      pressure, and serum lipid levels in postmenopausal women with impaired fasting
      glucose (IFG). METHODS: Twenty-eight postmenopausal women were assigned to an
      intervention group and twenty-one postmenopausal women to a control group. The
      intervention was provided for 12 weeks. Patients in the intervention group were
      asked to access a web site by using a cellular phone or to use the Internet
      directly and input their blood glucose and blood pressure levels weekly.
      Participants were sent the optimal recommendations weekly by both cellular phone
      and Internet. RESULTS: The intervention group had a mean decrease in systolic
      blood pressure (SBP) level of 8.1 mmHg but changes for the control group were not
      significant. There was a significant mean change in diastolic blood pressure
      (DBP) level for the intervention group (-7.7 mmHg). The mean change in the
      control group was not significant. CONCLUSION: This educational intervention
      using the Internet and a SMS by cellular phone improved levels of SBP and DBP in
      postmenopausal women with IFG.

PMID- 22143223
TI  - Biological and chemical sensors based on graphene materials.
AB  - Owing to their extraordinary electrical, chemical, optical, mechanical and
      structural properties, graphene and its derivatives have stimulated exploding
      interests in their sensor applications ever since the first isolation of free
      standing graphene sheets in year 2004. This article critically and
      comprehensively reviews the emerging graphene-based electrochemical sensors,
      electronic sensors, optical sensors, and nanopore sensors for biological or
      chemical detection. We emphasize on the underlying detection (or signal
      transduction) mechanisms, the unique roles and advantages of the used graphene
      materials. Properties and preparations of different graphene materials, their
      functionalizations are also comparatively discussed in view of sensor
      development. Finally, the perspective and current challenges of graphene sensors
      are outlined (312 references).

PMID- 22143224
TI  - Downstream resource utilization following hybrid cardiac imaging with an
      integrated cadmium-zinc-telluride/64-slice CT device.
AB  - PURPOSE: Low yield of invasive coronary angiography and unnecessary coronary
      interventions have been identified as key cost drivers in cardiology for
      evaluation of coronary artery disease (CAD). This has fuelled the search for
      noninvasive techniques providing comprehensive functional and anatomical
      information on coronary lesions. We have evaluated the impact of implementation
      of a novel hybrid cadmium-zinc-telluride (CZT)/64-slice CT camera into the daily
      clinical routine on downstream resource utilization. METHODS: Sixty-two patients
      with known or suspected CAD were referred for same-day single-session hybrid
      evaluation with CZT myocardial perfusion imaging (MPI) and coronary CT
      angiography (CCTA). Hybrid MPI/CCTA images from the integrated CZT/CT camera
      served for decision-making towards conservative versus invasive management. Based
      on the hybrid images patients were classified into those with and those without
      matched findings. Matched findings were defined as the combination of MPI defect
      with a stenosis by CCTA in the coronary artery subtending the respective
      territory. All patients with normal MPI and CCTA as well as those with isolated
      MPI or CCTA finding or combined but unmatched findings were categorized as "no
      match". RESULTS: All 23 patients with a matched finding underwent invasive
      coronary angiography and 21 (91%) were revascularized. Of the 39 patients with no
      match, 5 (13%, p < 0.001 vs matched) underwent catheterization and 3 (8%, p <
      0.001 vs matched) were revascularized. CONCLUSION: Cardiac hybrid imaging in CAD
      evaluation has a profound impact on patient management and may contribute to
      optimal downstream resource utilization.

PMID- 22143225
TI  - Evaluating the effective numbers of independent tests and significant p-value
      thresholds in commercial genotyping arrays and public imputation reference
      datasets.
AB  - Current genome-wide association studies (GWAS) use commercial genotyping
      microarrays that can assay over a million single nucleotide polymorphisms (SNPs).
      The number of SNPs is further boosted by advanced statistical genotype-imputation
      algorithms and large SNP databases for reference human populations. The testing
      of a huge number of SNPs needs to be taken into account in the interpretation of
      statistical significance in such genome-wide studies, but this is complicated by
      the non-independence of SNPs because of linkage disequilibrium (LD). Several
      previous groups have proposed the use of the effective number of independent
      markers (M(e)) for the adjustment of multiple testing, but current methods of
      calculation for M(e) are limited in accuracy or computational speed. Here, we
      report a more robust and fast method to calculate M(e). Applying this efficient
      method [implemented in a free software tool named Genetic type 1 error calculator
      (GEC)], we systematically examined the M(e), and the corresponding p-value
      thresholds required to control the genome-wide type 1 error rate at 0.05, for 13
      Illumina or Affymetrix genotyping arrays, as well as for HapMap Project and 1000
      Genomes Project datasets which are widely used in genotype imputation as
      reference panels. Our results suggested the use of a p-value threshold of ~10(-7)
      as the criterion for genome-wide significance for early commercial genotyping
      arrays, but slightly more stringent p-value thresholds ~5 * 10(-8) for current or
      merged commercial genotyping arrays, ~10(-8) for all common SNPs in the 1000
      Genomes Project dataset and ~5 * 10(-8) for the common SNPs only within genes.

PMID- 22143226
TI  - Snakebite neglect rampant in Africa.

PMID- 22143228
TI  - Climate change poses health threats in Arctic.

PMID- 22143227
TI  - Impact of remuneration and organizational factors on completing preventive
      manoeuvres in primary care practices.
AB  - BACKGROUND: Several jurisdictions attempting to reform primary care have focused
      on changes in physician remuneration. The goals of this study were to compare the
      delivery of preventive services by practices in four primary care funding models
      and to identify organizational factors associated with superior preventive care.
      METHODS: In a cross-sectional study, we included 137 primary care practices in
      the province of Ontario (35 fee-for-service practices, 35 with salaried
      physicians [community health centres], 35 practices in the new capitation model
      [family health networks] and 32 practices in the established capitation model
      [health services organizations]). We surveyed 288 family physicians. We reviewed
      4108 randomly selected patient charts and assigned prevention scores based on the
      proportion of eligible preventive manoeuvres delivered for each patient. RESULTS:
      A total of 3284 patients were eligible for at least one of six preventive
      manoeuvres. After adjusting for patient profile and contextual factors, we found
      that, compared with prevention scores in practices in the new capitation model,
      scores were significantly lower in fee-for-service practices (beta estimate for
      effect on prevention score = -6.3, 95% confidence interval [CI] -11.9 to -0.6)
      and practices in the established capitation model (beta = -9.1, 95% CI -14.9 to 
      3.3) but not for those with salaried remuneration (beta = -0.8, 95% CI -6.5 to
      4.8). After accounting for physician characteristics and organizational
      structure, the type of funding model was no longer a statistically significant
      factor. Compared with reference practices, those with at least one female family
      physician (beta = 8.0, 95% CI 4.2 to 11.8), a panel size of fewer than 1600
      patients per full-time equivalent family physician (beta = 6.8, 95% CI 3.1 to
      10.6) and an electronic reminder system (beta = 4.6, 95% CI 0.4 to 8.7) had
      superior prevention scores. The effect of these three factors was largely but not
      always consistent across the funding models; it was largely consistent across the
      preventive manoeuvres. INTERPRETATION: No funding model was clearly associated
      with superior preventive care. Factors related to physician characteristics and
      practice structure were stronger predictors of performance. Practices with one or
      more female physicians, a smaller patient load and an electronic reminder system
      had superior prevention scores. Our findings raise questions about reform
      initiatives aimed at increasing patient numbers, but they support the adoption of
      information technology.

PMID- 22143229
TI  - Nothing cutting edge about Canadian ehealth strategy, critics say.

PMID- 22143230
TI  - Europe clamps down on antibiotic misuse.

PMID- 22143231
TI  - Is Clostridium difficile infection still a problem for hospitals?

PMID- 22143232
TI  - Enrolment in primary care networks: impact on outcomes and processes of care for
      patients with diabetes.
AB  - BACKGROUND: Primary care networks are a newer model of primary care that focuses
      on improved access to care and the use of multidisciplinary teams for patients
      with chronic disease. We sought to determine the association between enrolment in
      primary care networks and the care and outcomes of patients with diabetes.
      METHODS: We used administrative health care data to study the care and outcomes
      of patients with incident and prevalent diabetes separately. For patients with
      prevalent diabetes, we compared those whose care was managed by physicians who
      were or were not in a primary care network using propensity score matching. For
      patients with incident diabetes, we studied a cohort before and after primary
      care networks were established. Each cohort was further divided based on whether
      or not patients were cared for by physicians enrolled in a network. Our primary
      outcome was admissions to hospital or visits to emergency departments for
      ambulatory care sensitive conditions specific to diabetes. RESULTS: Compared with
      patients whose prevalent diabetes is managed outside of primary care networks,
      patients in primary care networks had a lower rate of diabetes-specific
      ambulatory care sensitive conditions (adjusted incidence rate ratio 0.81, 95%
      confidence interval [CI] 0.75 to 0.87), were more likely to see an
      ophthalmologist or optometrist (risk ratio 1.19, 95% CI 1.17 to 1.21) and had
      better glycemic control (adjusted mean difference -0.067, 95% CI -0.081 to 
      0.052). INTERPRETATION: Patients whose diabetes was managed in primary care
      networks received better care and had better clinical outcomes than patients
      whose condition was not managed in a network, although the differences were very
      small.

PMID- 22143233
TI  - Managing pulmonary embolism using prognostic models: future concepts for primary
      care.

PMID- 22143236
TI  - 100 years. Looking forward: touch.

PMID- 22143235
TI  - The effect of hospital-acquired infection with Clostridium difficile on length of
      stay in hospital.
AB  - BACKGROUND: The effect of hospital-acquired infection with Clostridium difficile
      on length of stay in hospital is not yet fully understood. We determined the
      independent impact of hospital-acquired infection with C. difficile on length of
      stay in hospital. METHODS: We conducted a retrospective observational cohort
      study of admissions to hospital between July 1, 2002, and Mar. 31, 2009, at a
      single academic hospital. We measured the association between infection with
      hospital-acquired C. difficile and time to discharge from hospital using Kaplan
      Meier methods and a Cox multivariable proportional hazards regression model. We
      controlled for baseline risk of death and accounted for C. difficile as a time
      varying effect. RESULTS: Hospital-acquired infection with C. difficile was
      identified in 1393 of 136,877 admissions to hospital (overall risk 1.02%, 95%
      confidence interval [CI] 0.97%-1.06%). The crude median length of stay in
      hospital was greater for patients with hospital-acquired C. difficile (34 d) than
      for those without C. difficile (8 d). Survival analysis showed that hospital
      acquired infection with C. difficile increased the median length of stay in
      hospital by six days. In adjusted analyses, hospital-acquired C. difficile was
      significantly associated with time to discharge, modified by baseline risk of
      death and time to acquisition of C. difficile. The hazard ratio for discharge by
      day 7 among patients with hospital-acquired C. difficile was 0.55 (95% CI 0.39
      0.70) for patients in the lowest decile of baseline risk of death and 0.45 (95%
      CI 0.32-0.58) for those in the highest decile; for discharge by day 28, the
      corresponding hazard ratios were 0.74 (95% CI 0.60-0.87) and 0.61 (95% CI 0.53
      0.68). INTERPRETATION: Hospital-acquired infection with C. difficile
      significantly prolonged length of stay in hospital independent of baseline risk
      of death.

PMID- 22143237
TI  - Rash and loss of vision in a 60-year-old woman with systemic lupus erythematosus.

PMID- 22143238
TI  - Postherpetic pseudohernia.

PMID- 22143239
TI  - WHO signals intent to trim sails.

PMID- 22143241
TI  - Gene expression: splicing steps aside to consider its options.

PMID- 22143242
TI  - Human genetics: pleiotropic mutations.

PMID- 22143240
TI  - Cis-regulatory elements: molecular mechanisms and evolutionary processes
      underlying divergence.
AB  - Cis-regulatory sequences, such as enhancers and promoters, control development
      and physiology by regulating gene expression. Mutations that affect the function
      of these sequences contribute to phenotypic diversity within and between species.
      With many case studies implicating divergent cis-regulatory activity in
      phenotypic evolution, researchers have recently begun to elucidate the genetic
      and molecular mechanisms that are responsible for cis-regulatory divergence.
      Approaches include detailed functional analysis of individual cis-regulatory
      elements and comparing mechanisms of gene regulation among species using the
      latest genomic tools. Despite the limited number of mechanistic studies published
      to date, this work shows how cis-regulatory activity can diverge and how studies
      of cis-regulatory divergence can address long-standing questions about the
      genetic mechanisms of phenotypic evolution.

PMID- 22143244
TI  - A label-free cytosensor for the enhanced electrochemical detection of cancer
      cells using polydopamine-coated carbon nanotubes.
AB  - An electrochemical, label-free method was developed to detect folate receptor
      positive tumor cells by specific recognition of a polydopamine-coated carbon
      nanotubes-folate nanoprobe to cell-surface folate receptors. This strategy offers
      great promise to extend its application in studying the interaction of ligand and
      cell-surface receptor.

PMID- 22143245
TI  - Visualization of mitochondrial respiratory function using cytochrome c
      oxidase/succinate dehydrogenase (COX/SDH) double-labeling histochemistry.
AB  - Mitochondrial DNA (mtDNA) defects are an important cause of disease and may
      underlie aging and aging-related alterations (1,2). The mitochondrial theory of
      aging suggests a role for mtDNA mutations, which can alter bioenergetics
      homeostasis and cellular function, in the aging process (3). A wealth of evidence
      has been compiled in support of this theory (1,4), an example being the mtDNA
      mutator mouse (5); however, the precise role of mtDNA damage in aging is not
      entirely understood (6,7). Observing the activity of respiratory enzymes is a
      straightforward approach for investigating mitochondrial dysfunction. Complex IV,
      or cytochrome c oxidase (COX), is essential for mitochondrial function. The
      catalytic subunits of COX are encoded by mtDNA and are essential for assembly of
      the complex (Figure 1). Thus, proper synthesis and function are largely based on
      mtDNA integrity (2). Although other respiratory complexes could be investigated,
      Complexes IV and II are the most amenable to histochemical examination (8,9).
      Complex II, or succinate dehydrogenase (SDH), is entirely encoded by nuclear DNA
      (Figure 1), and its activity is typically not affected by impaired mtDNA,
      although an increase might indicate mitochondrial biogenesis (10-12). The
      impaired mtDNA observed in mitochondrial diseases, aging, and age-related
      diseases often leads to the presence of cells with low or absent COX activity
      (2,12-14). Although COX and SDH activities can be investigated individually, the
      sequential double-labeling method (15,16) has proved to be advantageous in
      locating cells with mitochondrial dysfunction (12,17-21). Many of the optimal
      constitutions of the assay have been determined, such as substrate concentration,
      electron acceptors/donors, intermediate electron carriers, influence of pH, and
      reaction time (9,22,23). 3,3'-diaminobenzidine (DAB) is an effective and reliable
      electron donor (22). In cells with functioning COX, the brown indamine polymer
      product will localize in mitochondrial cristae and saturate cells (22). Those
      cells with dysfunctional COX will therefore not be saturated by the DAB product,
      allowing for the visualization of SDH activity by reduction of nitroblue
      tetrazolium (NBT), an electron acceptor, to a blue formazan end product (9,24).
      Cytochrome c and sodium succinate substrates are added to normalize endogenous
      levels between control and diseased/mutant tissues (9). Catalase is added as a
      precaution to avoid possible contaminating reactions from peroxidase activity
      (9,22). Phenazine methosulfate (PMS), an intermediate electron carrier, is used
      in conjunction with sodium azide, a respiratory chain inhibitor, to increase the
      formation of the final reaction products (9,25). Despite this information, some
      critical details affecting the result of this seemly straightforward assay, in
      addition to specificity controls and advances in the technique, have not yet been
      presented.

PMID- 22143246
TI  - Left ventricular rupture in an anterior wall acute myocardial infarction with
      severe intra-ventricular gradient.
AB  - We report the case of a 72-year-old man with ST-elevation acute myocardial
      infarction and severe intra-ventricular gradient (>40 mmHg), who died with left
      ventricular rupture (LVR). We postulate that severe intra-ventricular gradient
      detectable at admission may be related to subsequent LVR and proposed as a risk
      factor for LVR.

PMID- 22143247
TI  - Traumatic aneurysm of the parietal branch of the superficial temporal artery :
      case presentation, diagnosis and review of the literature.

PMID- 22143248
TI  - Intrinsic control of sodium excretion in the distal nephron by inhibitory
      purinergic regulation of the epithelial Na(+) channel.
AB  - PURPOSE OF REVIEW: This review summarizes the new evidence for an intrinsic
      control system in the aldosterone-sensitive distal nephron in which purinergic
      signaling regulates sodium transport and governs renal sodium excretion. RECENT
      FINDINGS: Electrophysiological studies identify epithelial Na(+) channels (ENaC)
      as final effectors of purinergic signaling via P2Y(2) receptors in the distal
      nephron. Inhibition of ENaC by autocrine/paracrine purinergic signaling reduces
      sodium reabsorption allowing an appropriately graded pressure-natriuresis
      response when delivery of sodium to the distal nephron is high. Disruption of
      this intrinsic control mechanism decreases sodium excretion and therefore has a
      prohypertensive effect. Because purinergic inhibition of ENaC is tonic yet
      submaximal, its enhancement increases sodium excretion and therefore has an
      antihypertensive action. SUMMARY: Purinergic inhibitory regulation of ENaC is a
      key component of an intrinsic control system that enables the distal nephron to
      respond appropriately to the delivered load of sodium. This control system is
      physiologically important and functions in parallel with extrinsic control by the
      renin-angiotensin-aldosterone system, enabling sodium excretion to keep pace with
      sodium intake, especially when intake is high, and thereby maintaining arterial
      blood pressure. Disruption of intrinsic control of sodium transport by the distal
      nephron likely contributes to diseases such as arterial hypertension.

PMID- 22143250
TI  - PPARgamma as a therapeutic target in diabetic nephropathy and other renal
      diseases.
AB  - PURPOSE OF REVIEW: Peroxisome proliferator-activated receptor gamma (PPARgamma)
      is a ligand-activated nuclear transcription factor that regulates many important
      physiological processes including glucose and lipid metabolism, energy
      homeostasis, cell proliferation, inflammation, immunity and reproduction. The
      current review aims to summarize and discuss recent findings evaluating the
      protective effects of PPARgamma against kidney diseases with a focus on diabetic
      nephropathy. We will also delineate the potential underlying mechanisms. RECENT
      FINDINGS: PPARgamma plays important roles in renal physiology and
      pathophysiology. Agonists of PPARgamma exert protective effects against various
      kidney diseases including diabetic nephropathy, ischemic renal injury, IgA
      nephropathy, chemotherapy-associated kidney damage, polycystic kidney diseases
      and age-related kidney diseases via both systemic and renal actions. SUMMARY:
      PPARgamma agonists are effective in delaying and even preventing the progression
      of many renal diseases, especially diabetic nephropathy. PPARgamma may represent
      a promising target for the treatment of renal diseases.

PMID- 22143251
TI  - An algorithmic approach to peripheral artery disease in hemophilia: 
      extrapolation of management principles from noncoagulopathic patients.
AB  - The development of peripheral artery disease (PAD), a marker for systemic
      atherosclerosis and ischemic risk, is an increasingly important concern in the
      aging hemophilia population. A growing body of data suggests that an absence or
      deficiency of factor VIII or factor IX may not protect against atherogenesis,
      implying that the prevalence of PAD in men with hemophilia (MWH) may be higher
      than previously believed. This article describes special considerations in PAD
      screening, risk-factor modification, and management in older MWH.

PMID- 22143249
TI  - Vitamin D:  roles in renal and cardiovascular protection.
AB  - PURPOSE OF REVIEW: Great progress has been made in recent years in understanding
      the expanding roles of the vitamin D endocrine system beyond calcemic regulation,
      including pathophysiological actions in the kidney and the cardiovascular system.
      The purpose of this review is to update the recent advance regarding the effects
      of vitamin D and its analogs on the renal and cardiovascular system. RECENT
      FINDINGS: Vitamin D deficiency is not only widely associated with chronic kidney
      disease and cardiovascular disease in humans, but may also accelerate the disease
      progression. Dysregulation of vitamin D metabolism caused by renal insufficiency
      contributes to the low vitamin D status. Preclinical and clinical studies have
      demonstrated impressive therapeutic outcome with low-calcemic vitamin D analogs
      in renal and cardiovascular disease. The mechanism underlying the renal and
      cardiovascular protection involves regulation of multiple signaling pathways by
      vitamin D including nuclear factor kappaB, Wnt/beta-catenin and the renin
      angiotensin system. SUMMARY: The renal and cardiovascular protective activity of
      vitamin D revealed in recent studies has profound clinical implications.
      Nutritional correction of vitamin D deficiency and treatment with vitamin D
      analogs could be therapeutic options for renal and cardiovascular problems. New
      vitamin D analogs with better renal and cardiovascular therapeutic efficacy are
      highly desired. More randomized trials are needed to address these issues.

PMID- 22143252
TI  - Carbon monoxide-releasing molecule-2 decreases fibrinolysis in vitro and in vivo
      in the rabbit.
AB  - Administration of carbon monoxide derived from carbon monoxide-releasing
      molecules (CORMs) have been demonstrated to enhance coagulation and diminish
      fibrinolysis in vitro at small concentrations (100-200 MUmol/l) in human and
      rabbit plasma, whereas in vivo administration of large concentrations (>1400
      MUmol/l) of carbon monoxide has mildly increased bleeding time in vivo in rats.
      We sought to determine whether CORM-2 [tricarbonyldichlororuthenium (II) dimer]
      would improve coagulation and attenuate tissue-type plasminogen activator (tPA)
      mediated fibrinolysis in rabbit whole blood as determined in vitro by
      thrombelastography and in an in vivo preclinical rabbit model of ear bleeding
      time administered intravenous tPA (1 mg/kg). Addition of 200, 400 and 600 MUmol/l
      CORM-2 to whole blood significantly improved coagulation and attenuated
      fibrinolysis compared with blood without CORM-2. Rabbits administered CORM-2 (10
      mg/kg, 279 MUmol/l) had a small but significant decrease in bleeding time before
      tPA administration. Administration of tPA resulted in bleeding times more than
      six-fold greater than baseline in animals not exposed to CORM-2, whereas rabbits
      administered CORM-2 had significantly smaller (more than five-fold less) bleeding
      time values after tPA administration. CORM-2 administration significantly
      decreases fibrinolytic bleeding in the rabbit in vivo. Additional preclinical
      investigation of the effects of CORM-2 on coagulopathy (e.g. heparin-mediated or
      clopidogrel-mediated) utilizing this rabbit model are planned.

PMID- 22143253
TI  - Monoamines activate neuropeptide signaling cascades to modulate nociception in C.
      elegans: a useful model for the modulation of chronic pain?
AB  - Monoamines and neuropeptides interact to modulate key behaviors in most
      organisms. This review is focused on the interaction between octopamine (OA) and
      an array of neuropeptides in the inhibition of a simple, sensory-mediated
      aversive behavior in the C. elegans model system and describes the role of
      monoamines in the activation of global peptidergic signaling cascades. OA has
      been often considered the invertebrate counterpart of norepinephrine, and the
      review also highlights the similarities between OA inhibition in C. elegans and
      the noradrenergic modulation of pain in higher organisms.

PMID- 22143254
TI  - Independent degeneration of W and Y sex chromosomes in frog Rana rugosa.
AB  - The frog Rana rugosa uniquely possesses two different sex-determining systems of
      XX/XY and ZZ/ZW, separately in the geographic populations. The sex chromosomes of
      both types share the same origin at chromosome 7, and the structural differences
      between X and Y or Z and W were evolved through two inversions. In order to
      ascertain the mechanisms of degeneration of W and Y chromosomes, we
      gynogenetically produced homozygous diploids WW and YY and examined their
      viability. Tadpoles from geographic group N (W(N)W(N)) containing three
      populations died of edema at an early developmental stage within 10 days after
      hatching, while tadpoles from the geographic group K (W(K)W(K)) that contained
      two populations died of underdeveloped growth at a much later stage, 40-50 days
      after fertilization. On the contrary, W(N)W(K) and W(K)W(N) hybrid embryos were
      viable, successfully passed the two lethal stages, and survived till the
      attainment of adulthood. The observed survival implies that the lethal genes of
      the W chromosomes are not shared by the two groups and thus demonstrates their
      independent degeneration histories between the local groups. In sharp contrast, a
      sex-linked gene of androgen receptor gene (AR) from the W chromosome was down
      regulated in expression in both the groups, suggesting that inactivation of the W
      AR allele preceded divergence of the two groups and appearance of the lethal
      genes. Besides, the YY embryos died of cardiac edema immediately after hatching.
      The symptom of lethality and the stage of developmental arrest differed from
      those for either of WW lethal embryos. We therefore conclude that the W and Y
      chromosomes involve no evolutionary common scenario for degeneration.

PMID- 22143255
TI  - Conductive scanning probe microscopy of nanostructured Bi2Te3.
AB  - In order to explain the unique thermoelectric properties of bulk nanocomposite p
      type bismuth antimony telluride, its structural and electrical properties are
      investigated using transmission electron microscopy (TEM) and atomic force
      microscopy with a conductive probe (C-AFM). The material is observed to contain
      both nano- and micro-sized grains with sizes varying from 10 nm to 3 um. This
      unique structure promotes phonon scattering, thereby decreasing the thermal
      conductivity to below 1 W mK(-1) at room temperature. Moreover, the C-AFM data
      show that the electrical conductivity of nanosized grains is higher than the bulk
      value and reaches 1600 S cm(-1). This results in a moderate increment of the
      overall electrical conductivity, thereby increasing the figure of merit (ZT) up
      to 1.4 at 100  degrees C. In addition to demonstrating a powerful scanning probe
      microscopy (SPM) based investigation technique that requires minimal sample
      preparation, our findings contribute towards better understanding of the
      enhancement of thermoelectric properties of nanocomposite thermoelectric
      materials.

PMID- 22143256
TI  - Cardioprotective effect of a hemoglobin-based oxygen carrier on cold
      ischemia/reperfusion injury.
AB  - OBJECTIVES: The etiology of myocardial ischemia/reperfusion (I/R) injury is
      multifactorial, but activation of the innate immune system and the resulting
      inflammatory response are important components of I/R injury. The aim of this
      study was to investigate the protective effect of a hemoglobin-based oxygen
      carrier (HBOC) on cold I/R heart and to explore the underlying mechanisms.
      METHODS: Isolated Sprague-Dawley rat hearts were perfused in the Langendorff
      mode. After 30 min of basal perfusion, rat hearts were arrested with histidine
      tryptophan-ketoglutarate solution (HTKs) with or without an HBOC and
      hypothermically stored (4 degrees C) for 9 or 14 h, followed by 2 h of
      reperfusion. RESULTS: Compared with HTKs alone, the HBOC in HTKs greatly improved
      heart contraction and decreased infarct size, necrosis and apoptosis, which was
      related to the reduced expression of Toll-like receptor 2 (TLR 2), TLR 4, TNF
      alpha, IL-1beta and nuclear factor-kappaB (NF-kappaB) activation. CONCLUSIONS:
      Our results demonstrated that the HBOC protected isolated rat heart from cold I/R
      injury and this protection was associated with attenuation of the expression of
      the TLR 2 and TLR 4/NF-kappaB signaling pathway, which may down-regulate the
      inflammatory response.

PMID- 22143257
TI  - Effect of daily text messages on oral contraceptive continuation: a randomized
      controlled trial.
AB  - OBJECTIVE: To estimate whether daily educational text messages affect oral
      contraceptive pill (OCP) continuation at 6 months. METHODS: We randomized young
      women electing OCPs at an urban family planning health center to either routine
      care or routine care plus 180 days of daily educational text messages.
      Investigators masked to treatment allocation randomized participants who were not
      masked to treatment. The primary outcome measure was self-reported OCP
      continuation through a telephone call at 6 months (contacts between 5 and 8
      months). RESULTS: We enrolled 962 participants (480 intervention and 482 routine
      care) and obtained continuation data on 683 (346 and 337, respectively). At the
      follow-up, 64% of participants randomized to the intervention were still OCP
      users compared with 54% of the routine care group (P=.005). Continuation was
      highest in the intervention group if the interview took place while the
      intervention was ongoing (75% compared with 54%, P=.003); the effect of the
      intervention on continuation was less after the intervention ended (60% compared
      with 54%, P=.16). Participants receiving the intervention were more likely to
      continue oral contraception than control participants at 6 months (odds ratio
      1.44, 95% confidence interval 1.03-2.00) in analyses adjusted for age, race or
      ethnicity, age at coitarche, pregnancy history, and OCP experience. CONCLUSION:
      The use of daily educational text messages improves OCP continuation at 6 months
      over routine care alone. Ten women would need to receive this simple intervention
      to improve continuation in one. This effect is strongest in the women whose
      follow-up took place while the text intervention was ongoing. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00677703.

PMID- 22143259
TI  - Terahertz spectroscopy: a powerful new tool for the chemical sciences?
AB  - Terahertz spectroscopy is only now beginning to make its transition from initial
      development by physicists and engineers to broader use by chemists, materials
      scientists and biologists, thanks to the increasing availability of commercial
      terahertz spectrometers. With the unique insights that terahertz spectroscopy can
      provide into intermolecular bonding and crystalline matter, it could prove to be
      an invaluable addition to the chemist's analytical toolset. This tutorial review
      aims to give an introduction to terahertz spectroscopy, its techniques,
      equipment, current applications and potential for the chemical sciences to a
      broad readership.

PMID- 22143258
TI  - Effect of progestin compared with combined oral contraceptive pills on lactation:
      a randomized controlled trial.
AB  - OBJECTIVE: To estimate the effect of progestin-only compared with combined
      hormonal contraceptive pills on rates of breastfeeding continuation in postpartum
      women. Secondary outcomes include infant growth parameters, contraceptive method
      continuation, and patient satisfaction with breastfeeding and contraceptive
      method. METHODS: Postpartum breastfeeding women who desired oral contraceptives
      were randomly assigned to progestin-only and combined hormonal contraceptive
      pills. At 2 and 8 weeks postpartum, participants completed in-person
      questionnaires that assessed breastfeeding continuation and contraceptive use.
      Infant growth parameters including weight, length, and head circumference were
      assessed at 8 weeks postpartum. Telephone questionnaires assessing breastfeeding,
      contraceptive continuation, and satisfaction were completed at 3-7 weeks and 4
      and 6 months. Breastfeeding continuation was compared between groups using Cox
      proportional hazards regression. Differences in baseline demographic
      characteristics and in variables between the two intervention groups were
      compared using chi tests, Fisher exact test, or two-sample t tests as
      appropriate. RESULTS: Breastfeeding continuation rates at 8 weeks (progestin-only
      63.5%; combined hormonal 64.1%), contraceptive continuation, and infant growth
      parameters did not differ between users of progestin-only and combined hormonal
      contraceptive pills. Infant formula supplementation and maternal perception of
      inadequate milk supply were associated with decreased rates of breastfeeding in
      both groups. CONCLUSION: Choice of combined hormonal or progestin-only
      contraceptive pills administered 2 weeks postpartum did not adversely affect
      breastfeeding continuation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT01465022.

PMID- 22143260
TI  - Influence of the environment on adult CNS plasticity and repair.
AB  - During developmental critical periods, external stimuli are crucial for
      information processing, acquisition of new functions or functional recovery after
      CNS damage. These phenomena depend on the capability of neurons to modify their
      functional properties and/or their connections, generally defined as
      "plasticity". Although plasticity decreases after the closure of critical
      periods, the adult CNS retains significant capabilities for structural
      remodelling and functional adaptation. At the molecular level, structural
      modifications of neural circuits depend on the balance between intrinsic growth
      properties of the involved neurons and growth-regulatory cues of the
      extracellular milieu. Interestingly, experience acts on this balance, so as to
      create permissive conditions for neuritic remodelling. Here, we present an
      overview of recent findings concerning the effects of experience on cellular and
      molecular processes responsible for producing structural plasticity of neural
      networks or functional recovery after an insult to the adult CNS (e.g. traumatic
      injury, ischemia or neurodegenerative disease). Understanding experience
      dependent mechanisms is crucial for the development of tailored rehabilitative
      strategies, which can be exploited alone or in combination with specific
      therapeutic interventions to improve neural repair after damage.

PMID- 22143262
TI  - Mimicking an antimicrobial peptide polymyxin B by use of cyclodextrin.
AB  - Cyclodextrin derivatives prepared to mimic a membrane active antibacterial
      peptide polymyxin B strongly permeabilized bacterial membrane and inhibited
      bacterial proliferation.

PMID- 22143261
TI  - Towards a platform PBPK model to characterize the plasma and tissue disposition
      of monoclonal antibodies in preclinical species and human.
AB  - The objectives of the following investigation were (1) development of a
      physiologically based pharmacokinetic (PBPK) model capable of characterizing the
      plasma and tissue pharmacokinetics (PK) of nonspecific or antigen specific
      monoclonal antibodies (mAbs) in wild type, FcRn knockout, tumor bearing and non
      tumor bearing mice and (2) evaluation of the scale up potential of the model by
      characterizing the mouse, rat, monkey and human plasma PK of mAbs,
      simultaneously. A PBPK model containing 15 tissues, a carcass and a tumor
      compartment was developed by modifying/augmenting previously published PBPK
      models. Each tissue compartment was subdivided into plasma, blood cell,
      endothelial, interstitial and cellular sub-compartments. Each tissue was
      connected through blood and lymph flow to the systemic circulation. Lymph flow
      was set to a value 500 times lower than plasma flow and vascular reflection
      coefficients for each tissue were adjusted according to their vascular pore size.
      In each tissue endothelial space, mAb entered via pinocytosis and the interaction
      of FcRn with mAb was described by on and off rates. FcRn bound mAb was recycled
      and unbound mAb was eliminated by a first order process (K(deg)). The PBPK model
      was simultaneously fit to the following datasets to estimate four system
      parameters: (1) plasma and tissue PK of nonspecific mAb in wild type mouse with
      or without simultaneous intravenous immunoglobulin (IVIG) administration, (2)
      plasma and tissue PK of nonspecific mAb in FcRn knockout mouse, (3) plasma and
      tissue PK of nonspecific mAb in tumor bearing mouse, (4) plasma and tissue PK of
      tumor antigen specific mAb in tumor bearing mouse, and (5) plasma PK of mAb in
      rat, monkey and human. The model was able to characterize all the datasets
      reasonably well with a common set of parameters. The estimated value of the four
      system parameters i.e. FcRn concentration (FcRn), rate of pinocytosis per unit
      endosomal space (CL(up)), K(deg) and the proportionality constant (C_LNLF)
      between the rate at which antibody transfers from the lymph node compartment to
      the blood compartment and the plasma flow of the given species, were found to be
      4.98E-05 M (CV% = 11.1), 3.66E-02 l/h/l (%CV = 3.48), 42.9 1/h (%CV = 15.7) and
      9.1 (CV% > 50). Thus, a platform PBPK model has been developed that can not only
      simultaneously characterize mAb disposition data obtained from various previously
      published mouse PBPK models but is also capable of characterizing mAb disposition
      in various preclinical species and human.

PMID- 22143266
TI  - Motility: Baclofen effective for rumination and supragastric belching in a pilot
      study.

PMID- 22143263
TI  - Fading hepatic hemangiomas on multiphasic CT.
AB  - PURPOSE: To describe fading hemangiomas [substantially lower attenuation (>30 HU)
      than vascular pool in the portal venous phase (PVP)] and to determine their
      incidence and characteristics on multiphasic CT. METHODS: The study population
      composed of 168 hemangiomas (>=5 mm) in 114 consecutive patients which were
      imaged on multiphasic CT and also proved by diagnostic findings on MRI. The size
      of hemangiomas and CT attenuation number of the enhancing area within the
      hemangioma, liver parenchyma, and portal vein were measured on both arterial
      phase (AP) and PVP images. The rapidity of enhancement (slow, <50%; rapid, 50%
      99%; flash-filler, 100% filling in the AP) and association with arterioportal
      shunting (APS) were also determined by two independent reviewers. Imaging
      features were compared between fading and non-fading hemangiomas using Kruskal
      Wallis test. RESULTS: Of 168 hemangiomas, the enhancing area of 27 hemangiomas
      (16%, 27/168) showed substantially lower attenuation than that of PV (fading) in
      the PVP. When the attenuation difference was compared with the rapidity of
      enhancement, flash-fillers showed lower attenuation than PV in the PVP more
      frequently than both slow-fillers (P < 0.05) and rapid-fillers (P < 0.05). The
      proportion of fading hemangiomas was 52% (14/27) in flash-fillers, much more
      frequent than in rapid-fillers (4/27, 15%) as well as slow-fillers (9/27, 33.3%).
      The size of fading hemangiomas (17.9 +/- 4.5 mm) was significantly smaller than
      that of non-fading (24.2 +/- 3.6 mm) (P = 0.032). Although APS was more frequent
      in fading hemangiomas (55.6%, 15/27) than that of non-fading hemangiomas (37.6%,
      53/141), there was no statistically significant difference (P = 0.086).
      CONCLUSIONS: Sixteen percentage (27/168) of the hemangiomas in our study showed
      substantially lower attenuation than the portal vein in the PVP CT and this was
      more frequent in flash-fillers (52%, 14/27). The knowledge that fading does not
      preclude the diagnosis of hemangioma as well as of its high incidence in flash
      fillers is important, as flash-filling hemangiomas with fading may cause a
      diagnostic challenge in patients suspected to have hypervascular malignancy.

PMID- 22143268
TI  - Obesity: Unsaturated fatty acids aggravate acute pancreatitis.

PMID- 22143269
TI  - Ulcer: Prediction and prevention of peptic ulcer rebleeding.

PMID- 22143272
TI  - Hepatitis: HCV viremia correlates negatively with serum levels of cystatin C.

PMID- 22143271
TI  - IBS: Hypnotherapy--a wasted resource?

PMID- 22143273
TI  - Endoscopy: Nitinol self-expanding metal stents--safe and effective?

PMID- 22143275
TI  - Two loci in sorghum with NB-LRR encoding genes confer resistance to
      Colletotrichum sublineolum.
AB  - The aim of this work was to identify plant resistance genes to the sorghum
      anthracnose fungus Colletotrichum sublineolum. cDNA-AFLP transcript profiling on
      two contrasting sorghum genotypes inoculated with C. sublineolum generated about
      3,000 informative fragments. In a final set of 126 sequenced genes, 15 were
      identified as biotic stress related. Seven of the plant-derived genes were
      selected for functional analysis using a Brome mosaic virus-based virus-induced
      gene silencing (VIGS) system followed by fungal inoculation and quantitative real
      time PCR analysis. The candidate set comprised genes encoding resistance proteins
      (Cs1A, Cs2A), a lipid transfer protein (SbLTP1), a zinc finger-like transcription
      factor (SbZnTF1), a rice defensin-like homolog (SbDEFL1), a cell death related
      protein (SbCDL1), and an unknown gene harboring a casein kinase 2-like domain
      (SbCK2). Our results demonstrate that down-regulation of Cs1A, Cs2A, SbLTP1,
      SbZnF1 and SbCD1 via VIGS, significantly compromised the resistance response
      while milder effects were observed with SbDEFL1 and SbCK2. Expanded genome
      analysis revealed that Cs1A and Cs2A genes are located in two different loci on
      chromosome 9 closely linked with duplicated genes Cs1B and Cs2B, respectively.
      The nucleotide binding-leucine rich repeat (NB-LRR) encoding Cs gene sequence
      information is presently employed in regional breeding programs.

PMID- 22143274
TI  - The role of cancer-associated myofibroblasts in intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma is typically characterized by a dense
      desmoplastic stroma, of which cancer-associated myofibroblasts (which express
      alpha-smooth muscle actin), are a major cellular component. These stromal
      myofibroblasts have a crucial role in accelerating the progression of
      intrahepatic cholangiocarcinoma and in promoting resistance to therapy through
      interactive autocrine and paracrine signaling pathways that promote malignant
      cell proliferation, migration, invasiveness, apoptosis resistance and/or
      epithelial-mesenchymal transition. These changes correlate with aggressive tumor
      behavior. Hypoxic desmoplasia and aberrant Hedgehog signaling between stromal
      myofibroblastic cells and cholangiocarcinoma cells are also critical modulators
      of intrahepatic cholangiocarcinoma progression and therapy resistance. A novel
      strategy has been developed to achieve improved therapeutic outcomes in patients
      with advanced intrahepatic cholangiocarcinoma, based on targeting of multiple
      interactive pathways between cancer-associated myofibroblasts and intrahepatic
      cholangiocarcinoma cells that are associated with disease progression and poor
      survival. Unique organotypic cell culture and orthotopic rat models of
      cholangiocarcinoma progression are well suited to the rapid preclinical testing
      of this potentially paradigm-shifting strategy.

PMID- 22143276
TI  - In situ hybridization for the precise localization of transcripts in plants.
AB  - With the advances in genomics research of the past decade, plant biology has seen
      numerous studies presenting large-scale quantitative analyses of gene expression.
      Microarray and next generation sequencing approaches are being used to
      investigate developmental, physiological and stress response processes, dissect
      epigenetic and small RNA pathways, and build large gene regulatory networks(1-3).
      While these techniques facilitate the simultaneous analysis of large gene sets,
      they typically provide a very limited spatiotemporal resolution of gene
      expression changes. This limitation can be partially overcome by using either
      profiling method in conjunction with lasermicrodissection or fluorescence
      activated cell sorting(4-7). However, to fully understand the biological role of
      a gene, knowledge of its spatiotemporal pattern of expression at a cellular
      resolution is essential. Particularly, when studying development or the effects
      of environmental stimuli and mutants can the detailed analysis of a gene's
      expression pattern become essential. For instance, subtle quantitative
      differences in the expression levels of key regulatory genes can lead to dramatic
      phenotypes when associated with the loss or gain of expression in specific cell
      types.   Several methods are routinely used for the detailed examination of gene
      expression patterns. One is through analysis of transgenic reporter lines. Such
      analysis can, however, become time-consuming when analyzing multiple genes or
      working in plants recalcitrant to transformation. Moreover, an independent
      validation to ensure that the transgene expression pattern mimics that of the
      endogenous gene is typically required. Immunohistochemical protein localization
      or mRNA in situ hybridization present relatively fast alternatives for the direct
      visualization of gene expression within cells and tissues. The latter has the
      distinct advantage that it can be readily used on any gene of interest. In situ
      hybridization allows detection of target mRNAs in cells by hybridization with a
      labeled anti-sense RNA probe obtained by in vitro transcription of the gene of
      interest.  Here we outline a protocol for the in situ localization of gene
      expression in plants that is highly sensitivity and specific. It is optimized for
      use with paraformaldehyde fixed, paraffin-embedded sections, which give excellent
      preservation of histology, and DIG-labeled probes that are visualized by immuno
      detection and alkaline-phosphatase colorimetric reaction. This protocol has been
      successfully applied to a number of tissues from a wide range of plant species,
      and can be used to analyze expression of mRNAs as well as small RNAs(8-14).

PMID- 22143277
TI  - Lack of association between objectively assessed sleep disorders and inflammatory
      markers among kidney transplant recipients.
AB  - PURPOSE: In patients on dialysis, the results of studies examining the
      association between sleep disorders and inflammation are controversial. We
      assessed the association between inflammatory markers and different sleep
      disorders in a large sample of kidney transplant recipients. METHODS: Cross
      sectional study of 100 randomly selected kidney transplant patients who underwent
      one-night polysomnography ("sleep disorders evaluation in patients after kidney
      transplantation study") to diagnose obstructive sleep apnea (OSA) and periodic
      limb movements in sleep (PLMS). Athens Insomnia Scale (AIS) was utilized to
      assess the prevalence of insomnia. Sociodemographic information and data about
      medication, comorbidity and laboratory parameters were collected. Levels of
      inflammatory markers, such as C-reactive protein, serum albumin, white blood cell
      count, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), were
      measured. RESULTS: The mean age was 51 +/- 13 years, 43% were women, and the
      prevalence of diabetes was 19%. We found no significant difference in the levels
      of inflammatory markers between patients with versus without OSA and PLMS. Apnea
      hypopnea index showed a significant association with white blood cell count (rho
      = 0.23), and weak (rho < |0.15|), non-significant correlation with the other
      inflammatory markers. PLM index showed weak (rho < |0.15|), non-significant
      correlation with all markers of inflammation. The serum IL-6 level was
      significantly higher in patients with insomnia (AIS >= 10) than in non-insomniacs
      [median (IQR): 3.2(2.6-5.1) vs. 1.7(1.2-2.9) ng/l; P = 0.009]. The levels of
      other inflammatory markers were similar between insomniacs and non-insomniacs.
      CONCLUSIONS: We did not find any association between the presence of objectively
      assessed sleep disorders and inflammatory markers in kidney transplant patients.

PMID- 22143278
TI  - Myotonic dystrophies and the heart.
AB  - Myotonic dystrophy (MD) is a neuromuscular disorder of autosomal dominant
      inheritance, which is categorized by 2 main sub-types: type 1 (MD1) and type 2
      (MD2). This disease is characterized by myotonia and various multisytemic
      complications, most commonly of the cardiac, endocrine, and central nervous
      systems. In addition, cardiac abnormalities contribute to a significant morbidity
      and mortality in these patients. The cardiac abnormalities common to MD1 are
      conduction defects, such as first-degree atrioventricular block, arrhythmias, and
      other less common manifestations such as heart failure, ischemic heart disease,
      and mitral valve prolapse. Although these cardiac manifestations are also common
      in MD2, another complication that has been linked to MD2 is cardiomyopathy.
      Further study needs to be performed to better understand the pathology and
      management of these cardiac disorders associated with MD.

PMID- 22143279
TI  - Vascular Ehlers-Danlos syndrome: pathophysiology, diagnosis, and prevention and
      treatment of its complications.
AB  - The Ehlers-Danlos syndrome consists of a group of inherited connective tissue
      disorders caused by defects in the synthesis of collagen. The vascular type 4
      form of Ehlers-Danlos syndrome (VEDS) is associated with serious vascular
      complications in young adults, such as the spontaneous rupture of large-caliber
      and medium-caliber arteries, often without true aneurysm formation or dissection.
      VEDS is inherited as an autosomal dominant trait that is caused by mutations in
      the COL3A1 gene. It affects the synthesis and structure of the pro a1 (III) chain
      of collagen type III, which causes vascular wall weakness. The diagnosis of VEDS
      is made from major and minor clinical criteria and can be confirmed by
      abnormalities in procollagen production and molecular genetic testing. Recently,
      the results of a study using the b-blocker celiprolol demonstrated a reduction in
      vascular complications of VEDS. The mechanisms of benefit may be related to a
      reduction in vascular hemodynamic stress with exercise and/or through a reduction
      in transforming growth factor-b. Inhibitors of the renin-angiotensin system may
      also be beneficial in VEDS. Surgery may be beneficial in treating the
      complications of VEDS.

PMID- 22143280
TI  - Inappropriate sinus tachycardia:  current therapeutic options.
AB  - Inappropriate sinus tachycardia (IST) is an uncommon form of arrhythmia
      characterized by an increased heart rate that is out of proportion to a normal
      physiologic demand. The etiology of IST remains ill-defined and controversial.
      Clinical presentation of IST is highly variable, from isolated to sustained
      palpitations, and can cause deterioration in one's quality of life. IST is
      usually a diagnosis of exclusion and it is important to rule out other causes of
      sinus tachycardia before reaching a final diagnosis. Evaluation of cardiac
      autonomic reflex function is essential to support the diagnosis of IST. The
      treatment of IST aims to target the multiple mechanisms involved in this disease,
      and multidisciplinary management, including cardiac rehabilitation,
      pharmacotherapy, and occasionally radiofrequency modification of the sinus node,
      should be considered. The prognosis is usually benign, although regular follow-up
      is required to optimize therapy and prevent the onset of tachycardiomyopathy.

PMID- 22143281
TI  - Diagnostic imaging and risk stratification of patients with acute pulmonary
      embolism.
AB  - Pulmonary embolism (PE) is the third most common acute cardiovascular disease
      after myocardial infarction and stroke. The prompt diagnosis, risk
      stratification, and treatment of patients with acute PE can reduce mortality.
      Multidetector row computed tomography pulmonary angiography (CTPA) is the most
      common study used to make the diagnosis of acute PE. CTPA may additionally
      identify right heart dysfunction or alternative diagnoses. There is a growing
      body of evidence that computed tomography signs of right heart failure predict
      patients at higher risk of mortality. At the same time, CTPA has about a 6-fold
      greater whole body effective dose than ventilation-perfusion (V/Q) scintigraphy,
      and a much higher dose to breast tissue in particular. V/Q scintigraphy should be
      considered for patients with contraindications to iodinated contrast or for
      patients with normal chest radiographs, especially young women. Compression
      ultrasonography of the proximal lower extremities, an imaging study without
      ionizing radiation, should be considered for patients suspected of acute PE with
      signs of lower extremity deep venous thrombosis or for patients with negative
      CTPA or V/Q scan with discordant clinical probability. This article reviews
      factors affecting the selection of the best imaging test for a particular patient
      suspected of acute PE, performance characteristics of diagnostic imaging tests,
      and imaging findings that correlate with higher mortality.

PMID- 22143282
TI  - Contrast echocardiography:  applications and limitations.
AB  - Echocardiography is one of the most commonly used noninvasive imaging modalities
      in cardiology. Its portability, lack of ionizing radiation, excellent temporal
      and spatial resolution, and low cost make echocardiography an attractive
      technology. However, a significant proportion of patients have suboptimal images
      that decrease the diagnostic utility of echocardiography. One method to enhance
      the assessment of cardiac structure and function involves the administration of
      microbubble contrast agents. Capitalizing on interactions between microbubbles
      and ultrasound, imaging modalities that were specifically designed to enhance
      microbubble signal while suppressing tissue signal have been developed. These
      modalities can be used for either left ventricular opacification or myocardial
      perfusion imaging. The current applications of contrast echocardiography, along
      with the safety and limitations of the technology will be reviewed.

PMID- 22143283
TI  - Appropriate use of radionuclide imaging.
AB  - The growth of radionuclide imaging has raised well-founded concerns about
      potential overutilization. In response to the need for guidance, appropriate use
      criteria have been developed, which categorize specific clinical scenarios such
      as whether radionuclide imaging would be reasonable (appropriate) to perform, or
      whether the test would be performed for uncertain or inappropriate indications.
      Using these criteria, practice patterns may be evaluated and information provided
      to practitioners regarding test ordering. This information, along with clinical
      decision support, may provide a foundation to improve the utilization of cardiac
      imaging, preserving patient access to these procedures, but with an emphasis on
      cost-effectiveness and safety.

PMID- 22143284
TI  - Vitamin D: a cardioprotective agent?
AB  - Vitamin D is a fat-soluble vitamin that is naturally found in very few foods, is
      added to others, and is available as a dietary supplement. It is produced
      endogenously when ultraviolet light strikes the skin. Recent epidemiologic and
      experimental evidence has suggested that low vitamin D levels may play a role in
      various cardiovascular conditions, including coronary artery disease, congestive
      heart failure, valvular calcification, stroke, hypertension, and cognitive
      decline. Low vitamin D may lead to vascular smooth muscle cell proliferation,
      endothelial cell dysfunction, vascular and myocardial cell calcification, and
      increased inflammation. However, the data supporting a cardioprotective effect of
      vitamin D supplementation are very weak, and the large, controlled clinical
      trials now in progress should resolve this issue.

PMID- 22143286
TI  - High-internal-ionic liquid-phase emulsions.
AB  - High-internal-ionic liquid-phase emulsions were formed for the first time. The
      novel emulsions are very stable and do not involve any volatile organic solvent.
      They have great potential of applications in different fields, such as material
      synthesis, extraction, encapsulation, and chemical reactions.

PMID- 22143285
TI  - Linagliptin:  the newest dipeptidyl peptidase-4 inhibitor for type 2 diabetes
      mellitus.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitors are some of the newest medications in
      our armamentarium for the management of type 2 diabetes mellitus. Through
      inhibition of the DPP-4 enzyme, these agents increase the amount of circulating
      incretin hormones, leading to an increase in insulin release and a suppression of
      glucagon secretion. Linagliptin is the third DPP-4 inhibitor approved by the Food
      and Drug Administration in the United States. It has been studied as monotherapy
      and as an adjunctive therapy to other oral agents in a dual or triple combination
      regimen. Linagliptin lowers glycosylated hemoglobin by about 0.4% when used as
      monotherapy and by about 0.5% to 1.1% when used in combination with other oral
      antihyperglycemic agents. Since linagliptin is mostly eliminated via the
      enterohepatic system (80%) and not to a significant extent through renal
      excretion, dosage adjustment is not necessary in patients with renal impairment.
      Linagliptin also has a favorable safety profile; nasopharyngitis is one of the
      more common observed side effects. Given its encouraging safety and efficacy
      profile, linagliptin is a good alternative to the other 2 agents in this class,
      especially for patients with renal impairment. This article provides a review of
      the pharmacologic and pharmacokinetic properties of linagliptin. The differences
      among the 3 available DPP-4 inhibitors will also be examined.

PMID- 22143288
TI  - Radiation in vulvar cancer.
AB  - PURPOSE OF REVIEW: Vulvar cancer is a relatively rare gynecological malignancy
      afflicting elderly women. Although radiation therapy plays an important role, due
      to limited literature, treatment guidelines are less clearly defined. This
      article reviews the recent literature to discuss the current role of radiation
      therapy in the management of vulvar cancer. RECENT FINDINGS: There is a
      continuing scarcity of prospective and randomized controlled trials due to rarity
      of vulvar cancer. Most studies in the recent literature are largely retrospective
      in nature. However, it is evident from the available literature that combined
      chemoradiotherapy is slowly evolving as a new option in the management of locally
      advanced vulvar cancer (LAVC) reducing surgery-related morbidity. Various trials
      have tested the feasibility of concurrent chemoradiotherapy (CCRT) using
      different chemotherapeutic agents like cisplatin, 5-fluorouracil, mitomycin-C and
      have shown encouraging results. SUMMARY: For early-stage vulvar cancer, radiation
      therapy continues to play an adjuvant role. For LAVC, CCRT has emerged as a new
      feasible option both as preoperative and definitive treatment. Future CCRT trials
      should incorporate newer radiation therapy techniques like intensity-modulated
      radiation therapy to further reduce the radiation-related morbidity thus
      enhancing the tolerance of CCRT.

PMID- 22143287
TI  - Genetic background of Prop1(df) mutants provides remarkable protection against
      hypothyroidism-induced hearing impairment.
AB  - Hypothyroidism is a cause of genetic and environmentally induced deafness. The
      sensitivity of cochlear development and function to thyroid hormone (TH) mandates
      understanding TH action in this sensory organ. Prop1(df) and Pou1f1(dw) mutant
      mice carry mutations in different pituitary transcription factors, each resulting
      in pituitary thyrotropin deficiency. Despite the same lack of detectable serum
      TH, these mutants have very different hearing abilities: Prop1(df) mutants are
      mildly affected, while Pou1f1(dw) mutants are completely deaf. Genetic studies
      show that this difference is attributable to the genetic backgrounds. Using
      embryo transfer, we discovered that factors intrinsic to the fetus are the major
      contributor to this difference, not maternal effects. We analyzed Prop1(df)
      mutants to identify processes in cochlear development that are disrupted in other
      hypothyroid animal models but protected in Prop1(df) mutants by the genetic
      background. The development of outer hair cell (OHC) function is delayed, but
      Prestin and KCNQ4 immunostaining appear normal in mature Prop1(df) mutants. The
      endocochlear potential and KCNJ10 immunostaining in the stria vascularis are
      indistinguishable from wild type, and no differences in neurofilament or
      synaptophysin staining are evident in Prop1(df) mutants. The synaptic vesicle
      protein otoferlin normally shifts expression from OHC to IHC as temporary
      afferent fibers beneath the OHC regress postnatally. Prop1(df) mutants exhibit
      persistent, abnormal expression of otoferlin in apical OHC, suggesting delayed
      maturation of synaptic function. Thus, the genetic background of Prop1(df)
      mutants is remarkably protective for most functions affected in other hypothyroid
      mice. The Prop1(df) mutant is an attractive model for identifying the genes that
      protect against deafness.

PMID- 22143289
TI  - Parenting children with conduct disorder in Israel: caregiver burden and the
      sense of coherence.
AB  - The study examines the caregiver burden and sense of coherence among parents of
      300 children with conduct disorder, as compared to parents of 100 children
      without the disorder in Israel. Parents completed the Caregiver Burden Index and
      the Sense of Coherence Scale. The research findings showed significant
      differences between the two groups, with the parents of children with conduct
      disorder reporting a higher caregiver burden and lower sense of coherence than
      the parents of children with no disorder. The study highlights the need to
      provide professional support for parents of children with conduct disorder and to
      develop appropriate intervention programs for enhancing the parents' coping
      abilities.

PMID- 22143290
TI  - Facial nerve outcomes in facial nerve schwannomas.
AB  - OBJECTIVE: To better understand the characteristics and outcomes of facial nerve
      schwannomas (FNSs) over a 30-year period. STUDY DESIGN: Retrospective study.
      SETTING: Subspecialty practice at a tertiary hospital. PATIENTS: Fifty-six
      patients diagnosed with FNS over a 30-year period. METHODS: Preoperative data
      (audiologic data, facial nerve [FN] function, and patient symptoms),
      intraoperative data (tumor location, total versus subtotal resection, and FN
      status), and postoperative data (audiologic data, FN function, and recurrence)
      were collected. Mann-Whitney and chi2 analyses were done to determine which
      factors correlated with poor FN outcomes (defined as House-Brackmann >= 4).
      RESULTS: Of the 56 patients in this study, 53 (94.6%) underwent surgical
      resection of their FNS. Of those patients, 45 (84.9%) underwent total resection,
      and 8 (15.1%) underwent subtotal resection. Subtotal resection was associated
      with a statistically significant decreased risk of having postoperative HB grade
      >= 4 (odds ratio, 0.09; 95% confidence interval, 0.01-0.77; p = 0.028). Of those
      undergoing a subtotal resection, no patient had further tumor growth seen on
      postoperative magnetic resonance imaging (average time of last magnetic resonance
      imaging since operation, 44.9 mo). Tumor location was not statistically
      associated with poor FN outcome (all p > 0.05). Preoperative FN paralysis was the
      only preoperative clinical finding statistically associated with poor FN outcomes
      (p = 0.004). CONCLUSION: We have identified multiple characteristics of FNS as
      well as multiple factors associated with increased statistical risk of poor FN
      outcomes.

PMID- 22143291
TI  - Do high-speed drills generate high-frequency noise in mastoid surgery?
AB  - BACKGROUND: The introduction of increasingly high speed drills for mastoid
      surgery has heightened the concern that cochlea damage may occur in both the
      operated and nonoperated ear. It has been observed clinically that this damage
      could be associated with frequencies above 8,000 Hz and that, to observe these
      changes, high-frequency audiometry should be performed. Previous studies have
      investigated noise transmission to the cochlea at frequencies below 4,000 Hz
      only. There having been, until recently, limitations to the equipment available
      to measure higher frequencies. OBJECTIVE: To define the characteristics of noise
      transmitted to the cochlea during drilling of temporal bone, specifically in the
      higher frequency ranges up to 20,000 Hz. METHODS: Cleaned temporal bones were
      fitted with 3 mutually perpendicular accelerometers, capable of measuring
      frequencies in the range 500 to 20,000 Hz. The system was calibrated using a
      Kamplex Audio Traveller AA220 pure tone audiometer, and accelerometer outputs
      were recorded on a personal computer at a sampling frequency of 102.4 kHz per
      channel. The magnitude of the noise transmitted to the cochlea was determined for
      a range of burrs. RESULTS: Maximum transmission of sound was 108 dBA at 4,000 Hz
      using a 6.5-mm burr on the cortical mastoid bone. The average results showed that
      the sound transmission tailed off at the higher frequencies dropping to 84 dBA at
      8,000 Hz and 40 dBA at 16,000 Hz. CONCLUSION: The high-frequency hearing
      reduction noted in patients after mastoid surgery was shown not to be due to
      excessive high-frequency noise generated by drilling.

PMID- 22143292
TI  - The pathogenesis of acquired cholesteatoma of the human middle ear:  support for
      the migration hypothesis.
AB  - HYPOTHESIS: That acquired cholesteatoma of the human middle ear and mastoid
      process can be caused by migration of squamous epithelium from the tympanic
      membrane. OBJECTIVE: To provide histologic evidence in humans of the potential
      for medial epithelial migration toward the middle ear. BACKGROUND: The origin of
      cholesteatomas of the middle ear complex of humans is still not clearly
      understood. The most popular theory, the medial migration of squamous epithelium
      from the external auditory canal/tympanic membrane through a perforation of the
      tympanic membrane to form a cholesteatoma, was first proposed over a century ago
      independently by Bezold (1899) and Habermann (1899) based on their observations
      during surgery. Neither author had histologic proof. Despite much experimental
      efforts in animals, histologic evidence in the human continues to be the missing
      link. METHOD: We examined the histologic sections of the temporal bones of 60
      children aged 1 day to 12 years with evidence of acute otitis media. We present
      our findings in the temporal bones of 3 infants. RESULTS: We find evidence of the
      propensity of the squamous epithelium of the tympanic membrane particularly in
      the pars flaccida to become very active and to migrate medially toward the middle
      ear. CONCLUSION: Our concept is that this material supports the migration theory
      that cholesteatomas are formed by the medial migration of the stimulated squamous
      epithelium of the tympanic membrane.

PMID- 22143293
TI  - Re: "Histopathology after endolymphatic sac surgery for Meniere's syndrome".

PMID- 22143294
TI  - Surgery for outer ear canal exostoses and osteomata:  focusing on patient benefit
      and health-related quality of life.
AB  - OBJECTIVE: To analyze the impact of surgery for ear canal exostoses and osteomata
      on patients' health-related quality of life because the literature suggests that
      surgery cannot achieve excellent symptom control in all cases and has a
      considerable complication rate. STUDY DESIGN: Retrospective data collection.
      SETTING: Germany's largest university clinic for otorhinolaryngology and head and
      neck surgery. PATIENTS: Thirty-nine patients having received surgery for ear
      canal exostoses and osteomata. METHODS: Glasgow Benefit Inventory (GBI), a
      retrospective questionnaire well validated for measuring the effect of
      otorhinolaryngologic interventions on the health-related quality of life.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: GBI total scores and subscores.
      RESULTS: Thirty of the 39 patients returned a valid questionnaire (return rate,
      76.9%). The mean total GBI score was 14.6 (p < 0.001), suggesting a benefit from
      the operation. In contrast to the general subscale score (mean, 21.0; p < 0.001),
      the mean physical health score and the mean social support score were not
      significantly increased. Of all patients, 83.3% had a total GBI score higher than
      0, indicating a benefit from the operation. In 90% of the cases, patients were
      satisfied with the result of the operation, and 86.7% would again decide in favor
      of the operation. Most patients preoperatively experienced hearing loss, wax
      retention and recurrent otitis externa. Postoperatively, 70% of the patients were
      free of any complaints. The patients not satisfied were the only patients with
      negative GBI scores in the whole patient collective, and all had had
      complications from surgery. CONCLUSION: Surgery for ear canal exostoses and
      osteomata can significantly improve patients' health-related quality of life and
      leads to a high rate of patient satisfaction. Postoperative complications are the
      most important factor for a negative impact on the patient's health-related
      quality of life. Therefore, in the authors' opinion, only patients with symptoms
      should have surgery.

PMID- 22143295
TI  - New total ossicular replacement prostheses with a resilient joint:  experimental
      data from human temporal bones.
AB  - HYPOTHESIS: New flexible total ossicular prostheses with an integrated microjoint
      can compensate for large static displacements in the reconstructed ossicular
      chain. When properly designed, they can mimic the function of the joints of the
      intact chain and ensure good vibration transfer in both straight and bent
      conditions. BACKGROUND: Prosthesis dislocations and extrusions are frequently
      observed after middle ear surgery. They are mainly related to the altered
      distance between the coupling points because of large static eardrum
      displacements. METHODS: The new prostheses consist of 2 titanium shafts, which
      are incorporated into a silicone body. The sound transfer function and stapes
      footplate displacement at static loads were evaluated in human temporal bones
      after ossicular reconstruction using prostheses with 2 different silicones with
      different hardness values. The stiffness and bending characteristics of the
      prostheses were investigated with a quasi-static load. RESULTS: The sound
      transfer properties of the middle ears with the prostheses inserted under
      uncompressed conditions were comparable with those of ears with intact ossicular
      chains. The implant with the soft silicone had improved acoustic transfer
      characteristics over the implant with the hard silicone in a compressed state. In
      the quasi-static experiments, the minimum medial footplate displacement was found
      with the same implant. The bending characteristics depended on the silicone
      stiffness and correlated closely with the point and angle of the load incidence.
      CONCLUSION: The titanium prostheses with a resilient joint that were investigated
      in this study had good sound transfer characteristics under optimal conditions as
      well as in a compressed state. As a result of joint bending, the implants
      compensate for the small changes in length of the ossicular chain that occur
      under varying middle ear pressure. The implants require a stable support at the
      stapes footplate to function properly.

PMID- 22143296
TI  - Spanish and English language performance in bilingual children with cochlear
      implants.
AB  - OBJECTIVES: To document the factors that influence oral language performance in
      Spanish and English bilingual children with a cochlear implant. DESIGN: Using a
      repeated measures paradigm within a child, correlation and regression were used
      to analyze 4 factors that influence both Spanish and English receptive and
      expressive vocabulary, overall language skills, and articulation accuracy. The
      factors were age, duration of implantation, communication mode (total versus
      oral), and the amount of Spanish spoken at home. SUBJECTS: Twelve children
      between the ages of 49 and 106 months who had received a cochlear implant before
      36 months. All subjects scored within the normal range of the nonverbal IQ Leiter
      test. MAIN OUTCOME MEASURE: Spanish and English, receptive and expressive
      vocabulary, semantic and syntactic language skills, and articulation skills were
      measured using standardized tests, the Peabody Picture Vocabulary Test-IV, the
      Test de Vocabulario en Imagenes Peabody, the Expressive One Word Picture
      Vocabulary Test and Preschool Language Scale-IV, and the Goldman-Fristoe Test of
      Articulation-2. The amount of Spanish spoken at home was obtained via parental
      questionnaire. RESULTS: The raw scores of English language skills increased with
      increasing age and duration of implantation. Spanish skills were higher for
      higher Spanish spoken scores, and this effect was stronger when children were
      using oral communication mode. Lastly, oral communication mode had a positive
      effect on articulation accuracy. CONCLUSION: Age, duration of implantation, the
      amount of home language use, and communication mode influenced the overall
      language skills for Spanish and English bilingual children.

PMID- 22143297
TI  - Comparisons of auditory performance and speech intelligibility in children with
      cochlear implants placed using different approaches.
AB  - OBJECTIVE: To demonstrate whether there are differences in the outcomes of
      children with cochlear implants using the techniques between mastoidectomy with
      posterior tympanotomy (MPTA) and suprameatal approach (SMA). PATIENTS: A total of
      44 congenitally deaf children who underwent cochlear implantation before the age
      of 5 years at the Sixth Hospital Affiliated to Shanghai Jiao tong University from
      January 2005 to March 2008 were included in this study. Children with severe
      mental retardation or with cochlear malformations were excluded. Each group had
      22 patients; however, 4 patients in the SMA group and 5 in the MPTA group were
      not included in this study because the assessments for these patients were not
      available. INTERVENTIONS: All children were assessed before surgery and 6, 12,
      and 24 months after surgery with Categories of Auditory Performance (CAP) and
      Speech Intelligibility Rating (SIR). Each assessment was given by the child's
      speech therapist in the familiar environment of the child's home or school. At
      each interval, the CAP and SIR scores of each group were compared. RESULTS: For
      the both groups, CAP and SIR scores increased with the time of implant usage
      during the follow-up period after implantation. However, there were no
      significant differences in scores of CAP and SIR at the 4 time points between the
      SMA group and the MPTA group. CONCLUSION: Intelligible speech and auditory
      performance of children with cochlear implantation using the SMA were good. There
      were no differences between children implanted with the SMA technique versus the
      MPTA technique.

PMID- 22143298
TI  - Does meningitis after cochlear implantation remain a concern in 2011?
AB  - OBJECTIVE: There have been 283 cases of meningitis after cochlear implantation
      reported since 2002 to the CDC Database Manufacturer and User Facility Device
      Experience, resulting in 30 fatalities. This is the latest of a number of reports
      to track the continuing problem of meningitis occurring in cochlear implant
      users, mainly children. RESULTS: Although a number of these patients had received
      a device with a 2-piece electrode, the withdrawal of that particular device has
      not prevented further cases from occurring. There are many potential etiologic
      factors potentially involved in postimplantation bacterial meningitis; although
      some can be managed or eliminated, vaccination against the most prevalent causal
      organism, the streptococcus pneumoniae, seems to be a powerful tool against this
      uncommon but serious complication of cochlear implantation. CONCLUSION: Although
      up to 20 new cases of post-cochlear implantation meningitis continue to occur
      annually worldwide, considering the number of new devices implanted each year, it
      is expected that the incidence of this complication seems to be diminishing.

PMID- 22143299
TI  - Avulsed mastoid.

PMID- 22143300
TI  - Myringoplasty in simple chronic otitis media:  critical analysis of long-term
      results in a 1,000-adult patient series.
AB  - OBJECTIVES: Investigate the recurrence of chronic otitis media after primary and
      revision myringoplasty, compare long-term anatomic and audiologic results of
      underlay and overlay myringoplasty, and examine the prognostic factors. STUDY
      DESIGN: Retrospective study. PATIENTS: Approximately 1,040 adult patients with
      chronic simple otitis media undergoing a myringoplasty (overlay and underlay) by
      different surgeons at a single institution (ENT Department of Bergamo Ospedali
      Riuniti) between May 1999 and March 2009. METHODS: The cumulative recurrence rate
      of chronic otitis media during 10-year follow-up period was calculated using a
      Kaplan-Meier survival analysis. A multivariate analysis was used to evaluate
      different prognostic factors based on long-term outcome in myringoplasty.
      RESULTS: The overall 10-year graft success rate was 78% in 1,040 patients. The 10
      year recurrence rate of chronic otitis media was 15% in overlay myringoplasty and
      26% using the underlay technique (p < 0.05). In revision myringoplasty, the
      overlay technique showed a better success rate than underlay (p < 0.05).
      Significant recovery was observed in the air conduction thresholds and air-bone
      gaps in both groups with no statistical difference between techniques (p = 0.1).
      Multivariate analysis demonstrated that the underlay myringoplasty technique, a
      pathologic contralateral ear and an anterior or subtotal perforation, using a
      perichondrial graft or age of surgery younger than 40 years were statistically
      significant (p < 0.01) factors that negatively influenced the myringoplasty
      outcomes. CONCLUSION: More successful outcomes in primary and revision surgery
      for chronic otitis media occurred using overlay myringoplasty, although there
      were more minor postoperative complications. Both clinical and technical
      variables affected the success rate of myringoplasty.

PMID- 22143302
TI  - Preoperative, intraoperative, and postoperative results of bacterial culture from
      patients with chronic suppurative otitis media.
AB  - BACKGROUND: Cultures obtained from preoperative middle ear swabs from patients
      with chronic suppurative otitis media (CSOM) have traditionally been used to
      guide antibiotic selection. However, little is known about changes in the
      bacterial flora during surgery. OBJECTIVE: To analyze preoperative,
      intraoperative, and postoperative bacterial cultures of CSOM patients who
      underwent tympanomastoidectomy. METHODS: We retrospectively reviewed the medical
      records of 244 patients (113 male and 131 female subjects; 252 ears) diagnosed
      with CSOM between January 2006 and December 2008. Middle ear swabs and mastoid
      granulation tissue were collected preoperatively and intraoperatively,
      respectively. We also cultured middle ear swabs from patients with postoperative
      otorrhea. RESULTS: The most commonly identified preoperative pathogenic bacterial
      species was methicillin-resistant Staphylococcus aureus (MRSA). There were no
      statistical differences in prevalence of preoperative bacterial pathogens between
      patients with and without cholesteatoma. No bacteria were observed in 34.1% of
      preoperative or 76.6% of intraoperative cultures. Patients preoperatively
      positive for coagulase-negative Staphylococcus, S. aureus, or Pseudomonas
      aeruginosa remained positive intraoperatively. Of the patients preoperatively
      negative for bacteria and those positive for fungi, 6.9% and 20.0%, respectively,
      were positive for bacteria, including MRSA, intraoperatively. Of the patients
      that were preoperatively positive for bacteria, 16.7% to 50.0% was
      intraoperatively positive for different pathogens from previous results. Patients
      with postoperative otorrhea yielded the highest culture rates of MRSA,
      preoperatively, intraoperatively, and postoperatively. CONCLUSION: Although the
      similarities between preoperative and intraoperative culture results were
      relatively high, remaining or different pathogens also may have been present from
      intraoperative mastoid granulation tissue culture. Patients with preoperative
      MRSA were at high risk of postoperative otorrhea.

PMID- 22143301
TI  - Speech recognition and communication outcomes with cochlear implantation in Usher
      syndrome type 3.
AB  - BACKGROUND: Usher syndrome Type 3 (USH3) is an autosomal recessive disorder
      characterized by variable type and degree of progressive sensorineural hearing
      loss and retinitis pigmentosa. Cochlear implants are widely used among these
      patients. OBJECTIVES: To evaluate the results and benefits of cochlear
      implantation in patients with USH3. STUDY DESIGN: A nationwide multicenter
      retrospective review. MATERIALS AND METHODS: During the years 1995-2005, in 5
      Finnish university hospitals, 19 patients with USH3 received a cochlear implant.
      Saliva samples were collected to verify the USH3 genotype. Patients answered to 3
      questionnaires: Glasgow Benefit Inventory, Glasgow Health Status Inventory, and a
      self-made questionnaire. Audiological data were collected from patient records.
      RESULTS: All the patients with USH3 in the study were homozygous for the Finnish
      major mutation (p.Y176X). Either they had severe sensorineural hearing loss or
      they were profoundly deaf. The mean preoperative hearing level (pure-tone
      average, 0.5-4 kHz) was 110 +/- 8 dB hearing loss (HL) and the mean aided hearing
      level was 58 +/- 11 dB HL. The postoperative hearing level (34 +/- 9 dB HL) and
      word recognition scores were significantly better than before surgery. According
      to the Glasgow Benefit Inventory scores and Glasgow Health Status Inventory data
      related to hearing, the cochlear implantation was beneficial to patients with
      USH3. CONCLUSION: Cochlear implantation is beneficial to patients with USH3, and
      patients learn to use the implant without assistance.

PMID- 22143303
TI  - Canal conversion and reentry: a risk of Dix-Hallpike during canalith
      repositioning procedures.
AB  - OBJECTIVE: To determine the incidence, cause, and prevention of horizontal canal
      benign paroxysmal positional vertigo (H-BPPV) and reentry into the common crus
      during canalith repositioning procedures (CRPs). STUDY DESIGN: Prospective case
      series. SETTING: Academic tertiary referral center. PATIENTS: Forty-four patients
      with symptomatic posterior canalithiasis (P-BPPV) confirmed on Dix-Hallpike.
      INTERVENTION: Up to 5 CRP for initial P-BPPV and additional maneuvers for canal
      conversion or reentry in 1 session. MAIN OUTCOME MEASURES: Incidence and timing
      of onset of H-BPPV or common crus reentry and the outcome of treatment maneuvers.
      RESULTS: H-BPPV or reentry occurred during the Dix-Hallpike after a canal
      clearing CRP and affected 16% (7/44) of subjects. Approximately 87% (7/8) of
      reentry or conversion events occurred after the very first CRP. Geotropic H-BPPV
      occurred in 9% (4/44) overall but in 13% (4/30) whose P-BPPV was resolved by a
      single CRP. All were cleared with H-BPPV maneuvers, 3 of 4 resolving with a
      single Gufoni maneuver. Approximately 9% (4/44) of patients developed reentry of
      particles into the common crus. It was treated by raising the patient to the
      upright position. By waiting 15 minutes after treatment of reentry, a final
      normal Dix-Hallpike was obtained without causing reentry into any canal in all
      patients. CONCLUSION: If the first CRP clears the posterior canal, there is an
      elevated risk of reentry or canal conversion if another Dix-Hallpike is performed
      immediately. These complications can be treated by additional maneuvers; if
      unfamiliar with these techniques, the risk can be reduced by waiting at least 15
      minutes between repetitions of CRP.

PMID- 22143304
TI  - Audiologic phenotype of osteogenesis imperfecta:  use in clinical
      differentiation.
AB  - OBJECTIVES: To describe the audiologic phenotype in osteogenesis imperfecta (OI).
      STUDY DESIGN: Observational study. SETTING: Tertiary referral center. PATIENTS:
      One hundred eighty-two patients with genetically confirmed OI, aged 3 to 89
      years. INTERVENTION: Diagnostic hearing evaluation through otoadmittance and
      acoustic stapedius reflex measurements, pure tone, and speech audiometry. MAIN
      OUTCOME MEASURE(S): Prevalence, type, severity, symmetry, and audiometric
      configuration of the hearing loss in OI. Progression of hearing thresholds was
      determined by constructing age-related typical audiograms. RESULTS: Approximately
      52.2% of all OI patients demonstrated hearing loss unilaterally (7.7%) or
      bilaterally (44.5%). Pure conductive, mixed, and pure sensorineural hearing
      losses were observed in 8.5%, 37.8%, and 11.6% of OI ears, respectively. Multiple
      linear regression revealed that thresholds progressed by 0.5 dB/yr at 0.25 kHz to
      0.8 dB/yr at 0.8 kHz in the ears with conductive or mixed hearing loss. Pure
      sensorineural hearing loss progressed by less than 0.1 dB/yr at 0.25 kHz to 1.2
      dB/yr at 8.0 kHz. Audiometric configuration was predominantly flat (70.5%) in the
      ears with conductive/mixed loss and sloping (50.0%) in those with pure
      sensorineural loss. CONCLUSION: Patients with OI are at risk for hearing loss.
      The hearing loss in OI may initiate at a young age and is progressive. However,
      the rate of progression, as well as the hearing loss severity, onset, and
      configuration depend on the type of hearing loss, which may be conductive/mixed
      or pure sensorineural. For both types, age-related threshold audiograms are
      constructed and may help the clinician to estimate the course of the hearing loss
      in patients with OI. In addition, they may be valuable to distinguish between
      hearing loss associated with OI and other similar forms of hearing loss, such as
      in otosclerosis.

PMID- 22143305
TI  - I can do that: the impact of implicit theories on leadership role model
      effectiveness.
AB  - This research investigates the role of implicit theories in influencing the
      effectiveness of successful role models in the leadership domain. Across two
      studies, the authors test the prediction that incremental theorists ("leaders are
      made") compared to entity theorists ("leaders are born") will respond more
      positively to being presented with a role model before undertaking a leadership
      task. In Study 1, measuring people's naturally occurring implicit theories of
      leadership, the authors showed that after being primed with a role model,
      incremental theorists reported greater leadership confidence and less anxious
      depressed affect than entity theorists following the leadership task. In Study 2,
      the authors demonstrated the causal role of implicit theories by manipulating
      participants' theory of leadership ability. They replicated the findings from
      Study 1 and demonstrated that identification with the role model mediated the
      relationship between implicit theories and both confidence and affect. In
      addition, incremental theorists outperformed entity theorists on the leadership
      task.

PMID- 22143306
TI  - Do agreeableness and neuroticism explain age differences in the tendency to
      forgive others?
AB  - Previous research has shown that age is positively related to a dispositional
      tendency to forgive others. The present investigation tested the hypothesis that
      agreeableness and neuroticism partially mediate the association between age and
      forgivingness. Data from two representative cross-sectional samples of adults
      were used to test this hypothesis. Results from Study 1 (N = 962, age range: 19
      84 years) support the hypothesis, indicating that agreeableness and neuroticism
      explained, in part, age differences in tendencies to forgive. Study 2 (N = 451,
      age range: 20-83 years) replicated and extended the results by including
      transgression occurrences as a third mediator. The results showed that
      agreeableness and neuroticism explain the association between age and the
      tendency to forgive others over and above the effect of transgression
      occurrences.

PMID- 22143307
TI  - Unraveling the mystery of Brazilian jeitinho: a cultural exploration of social
      norms.
AB  - Two studies explore the structure and psychological makeup of jeitinho, a
      Brazilian indigenous construct associated with problem-solving strategies in
      strong hierarchies. Study 1 used a scenario approach with nonstudent participants
      and demonstrated that jeitinho can be described by a three-dimensional structure:
      corruption, creativity, and social norm breaking. Study 2 used individual and
      social norm scenarios in nonstudent samples and demonstrated that moral leniency
      is associated with more corruption and social norm breaking. Furthermore, only in
      the personal but not the social norm condition was greater social dominance
      orientation associated with more corruption and social norm breaking. Jeitinho is
      not a monolitical construct, but it is a complex sociocultural strategy that has
      distinct functional components at the personal and normative levels. Theoretical
      advances in the understanding of social norms and indigenous psychology by
      examining both culture-specific and general social-psychological processes are
      outlined.

PMID- 22143308
TI  - Ghosts of the past and dreams of the future: the impact of temporal focus on
      responses to contextual ingroup devaluation.
AB  - The authors investigated the impact of temporal focus on group members' responses
      to contextual ingroup devaluation. Four experimental studies demonstrated that
      following an induction of negative ingroup evaluation, participants primed with a
      past temporal focus reported behavioral intentions more consistent with this
      negative appraisal than participants primed with a future temporal focus. This
      effect was apparent only when a negative (but not a positive) evaluation was
      induced, and only among highly identified group members. Importantly, the
      interplay between temporal focus and group identification on relevant intentions
      was mediated by individual self-esteem, suggesting that focus on the future may
      be conducive to separating negative ingroup appraisals from individual self
      evaluations. Taken together, the findings suggest that high identifiers'
      responses to ingroup evaluations may be predicated on their temporal focus: A
      focus on the past may lock such individuals within their group's history, whereas
      a vision of the future may open up opportunities for change.

PMID- 22143309
TI  - Intergroup time bias and racialized social relations.
AB  - Within the framework of intergroup relations, the authors analyzed the time
      people spent evaluating ingroup and outgroup members. They hypothesized that
      White participants take longer to evaluate White targets than Black targets. In
      four experiments, White participants were slower to form impressions of White
      than of Black people; that is, they showed an intergroup time bias (ITB). In
      Study 1 (N = 60), the ITB correlated with implicit prejudice and homogeneity.
      Study 2 (N = 60) showed that the ITB was independent of the type of trait in
      question (nonstereotypical vs. stereotypical). Study 3 (N = 100) demonstrated
      that ITB correlates with racism measured 3 months beforehand, is independent of
      motivation to control prejudice, and is not an epiphenomenon of homogeneity. In
      Study 4 (N = 40) participants not only showed the ITB in a racialized social
      context but also displayed it following a minimal group manipulation.

PMID- 22143310
TI  - The effect of public social context on self-control: depletion for neuroticism
      and restoration for impression management.
AB  - The present study explores the role of personality in moderating the effect of
      public social context on self-control. The authors predicted that in public
      settings neuroticism would be associated with ego-depletion effects and
      individual differences in impression management (IM) would be associated with
      restoration effects. Three experiments supported the hypothesis. In Study 1
      neuroticism was associated with impaired self-control and IM was associated with
      enhanced self-control following an initial phase of working on a simple task in
      public (vs. in private). Study 2 replicated and extended these results to other
      domains of self-control. Study 3 explored whether public social context can
      cancel out early depletion effects. In this study, depleted participants engaged
      in a task that required self-control either alone or in public. As expected, the
      public settings were associated with restored self-control resources mostly among
      high IM individuals. Implications for self-control, neuroticism, and IM are
      discussed.

PMID- 22143311
TI  - The reaction mechanism of hydroxyethylphosphonate dioxygenase: a QM/MM study.
AB  - By employing ab initio quantum mechanical/molecular mechanical (QM/MM) and
      molecular dynamics (MD) simulations, we have provided further evidence against
      the previously proposed hydroperoxylation or hydroxylation mechanism of
      hydroxyethylphosphonate dioxygenase (HEPD). HEPD employs an interesting catalytic
      cycle based on concatenated bifurcations. The first bifurcation is based on the
      abstraction of hydrogen atoms from the substrate, which leads to a distal or
      proximal hydroperoxo species (Fe-OOH or Fe-(OH)O). The second and the third
      bifurcations refer to the carbon-carbon bond cleavage reaction. And this is
      achieved through a tridentate intermediate, or employing a proton-shuttle
      assisted mechanism, in which the residue Glu(176) or the Fe(IV)=O group serves as
      a general base. The reaction directions seem to be tunable and show significant
      environment dependence. This mechanism can provide a comprehensive interpretation
      for the seemingly contradicting experimental evidences and provide insight into
      the development of biochemistry and material sciences.

PMID- 22143312
TI  - Production and titering of recombinant adeno-associated viral vectors.
AB  - In recent years recombinant adeno-associated viral vectors (AAV) have become
      increasingly valuable for in vivo studies in animals, and are also currently
      being tested in human clinical trials. Wild-type AAV is a non-pathogenic member
      of the parvoviridae family and inherently replication-deficient. The broad
      transduction profile, low immune response as well as the strong and persistent
      transgene expression achieved with these vectors has made them a popular and
      versatile tool for in vitro and in vivo gene delivery. rAAVs can be easily and
      cheaply produced in the laboratory and, based on their favourable safety profile,
      are generally given a low safety classification. Here, we describe a method for
      the production and titering of chimeric rAAVs containing the capsid proteins of
      both AAV1 and AAV2. The use of these so-called chimeric vectors combines the
      benefits of both parental serotypes such as high titres stocks (AAV1) and
      purification by affinity chromatography (AAV2). These AAV serotypes are the best
      studied of all AAV serotypes, and individually have a broad infectivity pattern.
      The chimeric vectors described here should have the infectious properties of AAV1
      and AAV2 and can thus be expected to infect a large range of tissues, including
      neurons, skeletal muscle, pancreas, kidney among others. The method described
      here uses heparin column purification, a method believed to give a higher viral
      titer and cleaner viral preparation than other purification methods, such as
      centrifugation through a caesium chloride gradient. Additionally, we describe how
      these vectors can be quickly and easily titered to give accurate reading of the
      number of infectious particles produced.

PMID- 22143313
TI  - Comparative study of tibial posterior slope angle following cruciate-retaining
      total knee arthroplasty using one of three implants.
AB  - PURPOSE: Pre- and postoperative tibial posterior slope angles (PSAs) were
      assessed in patients who underwent cruciate-retaining total knee arthroplasty
      (TKA). MATERIAL AND METHODS: A total of 386 cruciate retaining TKA were performed
      in 308 patients and retrospectively reviewed. Based on the prostheses, 202 cases
      using NexGen were classified as group I, 120 cases using PFC sigma as group II,
      and 64 cases using Vanguard as group III. Postoperative PSA of groups I, II, and
      III were compared. RESULTS: In groups I, II, and III, postoperative PSA was 6.0,
      6.0, and 4.5, respectively (p < 0.001). Between preoperative measurement and
      final follow-up examination, mean knee score (59.7 to 97.3), function score (54.2
      to 90.5), and range of motion (ROM; 126.7 degrees  to 132.2 degrees ) improved.
      These three values did not differ significantly among groups. CONCLUSIONS: The 3
      degrees  slope of the Vanguard polyethylene insert caused the difference in PSAs.
      This design characteristic should be considered when using this implant in TKA.

PMID- 22143314
TI  - The effects of different weight-bearing regimes on press-fit cup stability: a
      randomised study with five years of follow-up using radiostereometry.
AB  - PURPOSE: There is little evidence to support immediate weight bearing after
      uncemented total hip arthroplasty (THA). METHODS: Thirty-seven patients with
      unilateral osteoarthritis of the hip received a press-fit cup. Cup stability was
      assessed with radiostereometry (RSA) over five years. Patients were randomised to
      immediate full weight bearing, or partial weight bearing for three months.
      RESULTS: At five years, we found no difference in micro-motion as assessed with
      radiostereometry. Numerically, there was more proximal translation and increased
      inclination with immediate weight bearing, but these values barely exceeded the
      precision limit for the method. Pooled data for the two groups revealed
      translations of 0.1-0.3 mm and rotations of 0.2-0.3 degrees  over the five year
      follow-up period. CONCLUSIONS: We found no adverse effects of immediate weight
      bearing after THA in relation to stability of these press-fit cups. Early
      mobilisation might have other advantages.

PMID- 22143315
TI  - Treatment of spondylodiscitis.
AB  - PURPOSE: Pyogenic infections of the spine are relatively rare with an incidence
      between 1:100,000 and 1:250,000 per year, but the incidence is increasing due to
      increases in average life-expectancy, risk factors, and medical comorbidities.
      The mean time in hospital varies from 30 to 57 days and the hospital mortality is
      reported to be 2-17%. This article presents the relevant literature and our
      experience of conservative and surgical treatment of pyogenic spondylodiscitis.
      METHOD: We have performed a review of the relevant literature and report the
      results of our own research in the diagnosis and treatment of pyogenic
      spondylodiscitis. We present a sequential algorithm for identification of the
      pathogen with blood cultures, CT-guided biopsies and intraoperative tissue
      samples. Basic treatment principles and indications for surgery and our surgical
      strategies are discussed. RESULTS: Recent efforts have been directed toward early
      mobilisation of patients using primary stable surgical techniques that lead to a
      further reduction of the mortality. Currently our hospital mortality in patients
      with spondylodiscitis is around 2%. With modern surgical and antibiotic
      treatment, a relapse of spondylodiscitis is unlikely to occur. In literature the
      relapse rate of 0-7% has been recorded. Overall the quality of life seems to be
      more favourable in patients following surgical treatment of spondylodiscitis.
      CONCLUSION: With close clinical and radiological monitoring of patients with
      spondylodiscitis, conservative and surgical therapies have become more
      successful. When indicated, surgical stabilisation of the infected segments is
      mandatory for control of the disease and immediate mobilisation of the patients.

PMID- 22143317
TI  - Anterior cruciate ligament deficiency leads to early instability of scaffold for
      cartilage regeneration: a controlled laboratory ex-vivo study.
AB  - PURPOSE: The affect of anterior cruciate ligament (ACL) integrity on the early
      postoperative stability of a collagen type-I gel scaffold was investigated. The
      value of fibrin glue for graft fixation in ACL deficient porcine knees over a
      simulated early postoperative period was also studied. METHODS: Full-thickness
      articular cartilage defects (11 * 6 mm) were created on the medial femoral
      condyle of 80 porcine knees. The ACL was left intact or completely transected in
      each of 40 knees. Gel plugs were tested in each group: press-fitting only in 20
      specimens and press-fitting plus fibrin glue in 20 specimens. Each knee underwent
      2,000 cycles in a validated ex-vivo continuous passive motion model. RESULTS:
      Press-fit-only fixation grafts in knee specimens with an intact ACL showed
      significantly superior stability than that in ACL deficient knees (p = 0.01). In
      ACL deficient knees, grafts fixed with press-fitting plus fibrin glue showed
      significantly superior stability than those using press-fit only fixation (p =
      0.01). Press-fitting plus fibrin glue fixation showed no significant differences
      in worn surface area between knee specimens with intact and deficient ACL.
      CONCLUSIONS: ACL deficiency led to early scaffold instability in an ex-vivo
      porcine knee model. Fibrin glue in ACL deficient knees led to additional graft
      stability. These findings indicated that cartilage regenerative techniques may
      give optimum results in ACL intact knees.

PMID- 22143318
TI  - The relationship of active ghrelin levels and intrauterine growth in preterm
      infants.
AB  - OBJECTIVE: We examined the association of active ghrelin levels with birth
      weight, sex, and gestational age (GA) in small for GA (SGA) and appropriate for
      GA (AGA) preterm infants. METHODS: Active ghrelin levels were measured by ELISA
      method during the first five postnatal days in 38 preterm SGA infants and 32
      preterm AGA controls. RESULTS: Active ghrelin levels were significantly higher in
      preterm SGA infants than in preterm AGA controls (P < 0.01). Active ghrelin
      levels in preterms with birth weight <1500 g were statistically higher than those
      over 1500 g. Active ghrelin levels in preterms <= 34 gestational weeks were
      similar to those over 34 weeks. A negative correlation was detected between
      active ghrelin levels and birth weight (r = -0.561, P < 0.0001) as well as GA (r
      = -0.449, P < 0.0001). CONCLUSION: We found significantly higher active ghrelin
      levels in SGA preterms than those in AGA preterms and demonstrated a negative
      correlation between active ghrelin levels and birth weight in preterm infants.
      This was the first study showing a negative correlation between active ghrelin
      levels and birth weight in preterm infants.

PMID- 22143319
TI  - The role of sonoelastography in acute, subacute and chronic thyroiditis: a novel
      application of the method.
AB  - OBJECTIVE: Reports on sonoelastography, which provide an objective estimation of
      tissue elasticity, are scarce in terms of thyroiditis. The aim of this study was
      to prospectively assess the applicability of sonoelastography in different types
      of thyroiditis. DESIGN: The study assessed and compared the thyroid tissue
      stiffness in patients with acute thyroiditis (AT), subacute thyroiditis (SAT),
      and chronic autoimmune thyroiditis (CAT) with healthy control subjects (CS),
      followed up for 10 weeks. METHODS: The study group consisted of two patients with
      AT, 18 patients with SAT, 18 patients with CAT, and 40 CS matched for age and
      gender. Sonoelastography was performed at baseline, at a 4-week follow-up during
      treatment, and at 10 weeks following diagnosis and treatment initiation. RESULTS:
      Thyroid tissue stiffness was higher in SAT at baseline (214.26 +/- 32.5 kPa) in
      comparison with values recorded at a 4-week follow-up (45.92 +/- 17.4 kPa) and at
      10 weeks following diagnosis and treatment initiation (21.65 +/- 5.3 kPa, P <
      0.0001). Baseline thyroid stiffness in SAT was higher than that found in CAT
      (36.15 +/- 18.7 kPa, P < 0.0001) and CS (16.18 +/- 5.4 kPa, P < 0.0001). In the
      remission of SAT, thyroid stiffness was lower than that found in CAT (P = 0.006),
      while it was higher than that in CS (P = 0.0008). No difference was observed
      between thyroid stiffness in SAT at 4-week follow-up and in CAT. Patients with
      CAT presented higher thyroid stiffness than CS (P < 0.0001), which was not
      influenced by L-thyroxine treatment. Thyroid stiffness in patients with AT was
      216.6 and 241.9 kPa at baseline; after treatment, it decreased to 17.93 and
      85.348 kPa respectively. CONCLUSIONS: Sonoelastography may assist in the
      diagnosis and treatment monitoring of AT, SAT and CAT, as well as in the
      differentiation of the various types of thyroiditis.

PMID- 22143320
TI  - Mentoring highly aggressive children: pre-post changes in mentors' attitudes,
      personality, and attachment tendencies.
AB  - This study examined the degree to which mentoring highly aggressive children was
      associated with changes in mentors' attitudes, personality, and attachment
      tendencies. Participants were 102 college students who each mentored an
      aggressive, high-risk child across three academic semesters (spring, fall,
      spring). We examined pre- to post-mentoring changes in attitudes about mentoring
      efficacy and future parenting, Big Five personality characteristics, and
      attachment tendencies. Mentors also rated the impact of the mentoring
      relationship in their lives, and both mentors and mentees rated support of the
      mentoring relationship. Results indicated a statistically significant decrease
      over time in mentors' ratings of self-efficacy, openness, conscientiousness,
      extraversion, and agreeableness. These findings held even when controlling for
      ratings of relationship impact. However, mentors who rated the mentoring
      relationship as supportive tended to experience increased openness,
      conscientiousness, and agreeableness and less attachment-related avoidance over
      time. Child-rated support negatively predicted mentors' post-mentoring attitudes
      toward future parenting. Discussed are the potential costs of mentoring highly
      aggressive children and strategies that could help increase benefits to mentors.

PMID- 22143321
TI  - Positive parenting practices associated with subsequent childhood weight change.
AB  - We aimed to identify positive parenting practices that set children on
      differential weight-trajectories. Parenting practices studied were cognitively
      stimulating activities, limit-setting, disciplinary practices, and parent warmth.
      Data from two U.S. national longitudinal data sets and linear and logistic
      regression were used to examine association of initial parenting practices with
      subsequent change in body mass index (BMI) Z-score and being overweight,
      stratified by income and gender. Lower change in BMI Z-score and lower likelihood
      of being or becoming overweight occurred among girls if parents engaged in
      cognitively stimulating activities or set bedtime; among low-income girls if
      parents helped with art and set bedtime; among high-income girls if they
      participated in dance or music, parents talked about nature or visited a museum
      or library, or parents had rules about number of hours for watching television;
      among low-income boys if they participated in dance or parents built something
      with them or set bedtime; and among high-income boys if they participated in
      dance or music. Greater expression of warmth was associated with lower change in
      BMI Z-score. Parenting practices facilitating cognitive stimulation, setting
      limits, and expressing warmth are associated with lower likelihood of being or
      becoming overweight and can be promoted by healthcare professionals.

PMID- 22143322
TI  - Examining the cultural context of youth mentoring: a systematic review.
AB  - While research in youth mentoring is extensive in the U.S., little research has
      explored its effectiveness in New Zealand, despite its growth in the past 20
      years. While arguments have been raised that overseas models may not fit all
      cultural contexts within New Zealand, there appears to be limited evidence
      supporting this contention. Further, little is known about associations between
      effectiveness and the cultural appropriateness of programs and research. This
      systematic review of youth mentoring programs in New Zealand is based on 26
      studies that met inclusion criteria. Of those, 14 had a significant proportion
      (15% or more) of indigenous Maori youth and six had a significant proportion of
      Pasifika (Pacific Islander) youth. While almost all programs and associated
      research were culturally appropriate to the overall New Zealand context, they
      tended to be less culturally appropriate for programs working with Maori and
      Pasifika youth. Further, there was a negative association between cultural
      appropriateness and program effectiveness.

PMID- 22143323
TI  - Youth mentoring: new areas for research.

PMID- 22143324
TI  - Protection against methylglyoxal-derived AGEs by regulation of glyoxalase 1
      prevents retinal neuroglial and vasodegenerative pathology.
AB  - AIMS/HYPOTHESIS: Methylglyoxal (MG) is an important precursor for AGEs. Normally,
      MG is detoxified by the glyoxalase (GLO) enzyme system (including component
      enzymes GLO1 and GLO2). Enhanced glycolytic metabolism in many cells during
      diabetes may overpower detoxification capacity and lead to AGE-related pathology.
      Using a transgenic rat model that overexpresses GLO1, we investigated if this
      enzyme can inhibit retinal AGE formation and prevent key lesions of diabetic
      retinopathy. METHODS: Transgenic rats were developed by overexpression of full
      length GLO1. Diabetes was induced in wild-type (WT) and GLO1 rats and the animals
      were killed after 12 or 24 weeks of hyperglycaemia. N epsilon)
      (Carboxyethyl)lysine (CEL), N(epsilon)-(carboxymethyl)lysine (CML) and MG-derived
      hydroimidazalone-1 (MG-H1) were determined by immunohistochemistry and by ultra
      performance liquid chromatography tandem mass spectrometry (UPLC-MSMS). Muller
      glia dysfunction was determined by glial fibrillary acidic protein (GFAP)
      immunoreactivity and by spatial localisation of the potassium channel Kir4.1.
      Acellular capillaries were quantified in retinal flat mounts. RESULTS: GLO1
      overexpression prevented CEL and MG-H1 accumulation in the diabetic retina when
      compared with WT diabetic counterparts (p < 0.01). Diabetes-related increases in
      Muller glial GFAP levels and loss of Kir4.1 at the vascular end-feet were
      significantly prevented by GLO1 overexpression (p < 0.05) at both 12- and 24-week
      time points. GLO1 diabetic animals showed fewer acellular capillaries than WT
      diabetic animals (p < 0.001) at 24 weeks' diabetes. CONCLUSIONS/INTERPRETATION:
      Detoxification of MG reduces AGE adduct accumulation, which, in turn, can prevent
      formation of key retinal neuroglial and vascular lesions as diabetes progresses.
      MG-derived AGEs play an important role in diabetic retinopathy.

PMID- 22143325
TI  - Brief report: genome sequence and construction of an infectious cDNA clone of
      Ribgrass mosaic virus from Chinese cabbage in Korea.
AB  - Ribgrass mosaic virus (RMV) has severely decreased the production and lowered
      quality of Chinese cabbage co-infected with Turnip mosaic virus (63.4%) in Korea.
      The complete genome sequence of RMV isolated from Brassica rapa ssp. pekinensis
      was determined. The full genome consisted of 6,304 nucleotides and showed
      sequence identities of 91.5-94.2% with the corresponding genome of other RMV
      strains. Full-length cDNA of RMV-Br was amplified by RT-PCR with a 5'-end primer
      harboring a T7 promoter sequence and a 3'-end RMV specific primer. Subsequently,
      the full-length cDNA was cloned into plasmid vectors. Capped transcripts
      synthesized from the cDNA clone were highly infectious and caused characteristic
      symptoms in B. rapa ssp. pekinensis and several indicator plants, similar to wild
      type RMV. Since there has not been found RMV resistant Chinese cabbage yet and
      the virus has been prevalent already throughout the natural fields of Korea, the
      identification of full sequence and development of infectious clone would help
      developing breeding program for RMV resistant crops.

PMID- 22143330
TI  - Nondialysis chronic kidney disease in 2011: Progression, prediction, populations
      and possibilities.
AB  - In 2011, studies of chronic kidney disease (CKD) were published in abundance. The
      articles selected here represent the growing appreciation of the importance of
      CKD as a modifier of outcomes, breakthroughs in understanding the pathobiology
      and genetics of specific conditions, and clinical trials of treatment strategies
      that offer hope to patients with CKD.

PMID- 22143332
TI  - Diabetes: Intensive glucose control in type 1 diabetes mellitus reduces risk of
      GFR loss.

PMID- 22143329
TI  - Genome-wide association studies of chronic kidney disease: what have we learned?
AB  - The past 3 years have witnessed a dramatic expansion in our knowledge of the
      genetic determinants of estimated glomerular filtration rate (eGFR) and chronic
      kidney disease (CKD). However, heritability estimates of eGFR indicate that we
      have only identified a small proportion of the total heritable contribution to
      the phenotypic variation. The majority of associations reported from genome-wide
      association studies identify genomic regions of interest and further work will be
      required to identify the causal variants responsible for a specific phenotype.
      Progress in this area is likely to stem from the identification of novel risk
      genotypes, which will offer insight into the pathogenesis of disease and
      potential novel therapeutic targets. Follow-up studies stimulated by findings
      from genome-wide association studies of kidney disease are already yielding
      promising results, such as the identification of an association between urinary
      uromodulin levels and incident CKD. Although this work is at an early stage,
      prospects for progress in our understanding of CKD and its treatment look more
      promising now than at any point in the past.

PMID- 22143334
TI  - Chronic kidney disease: Health burden of kidney disease recognized by UN.

PMID- 22143335
TI  - Visible light driven hydrogen production from a photo-active cathode based on a
      molecular catalyst and organic dye-sensitized p-type nanostructured NiO.
AB  - A molecular device with a photocathode for hydrogen generation has been
      successfully demonstrated, based on an earth abundant and inexpensive p-type
      semiconductor NiO, an organic dye P1 and a cobalt catalyst Co1.

PMID- 22143333
TI  - The renaissance of corticotropin therapy in proteinuric nephropathies.
AB  - Refractory nephrotic syndrome continues to be a therapeutic challenge despite
      advances in immunosuppression and blockade of the renin-angiotensin-aldosterone
      cascade. Adrenocorticotropic hormone (ACTH), a pituitary neuroimmunoendocrine
      polypeptide, was widely used in the 1950s as an effective therapy for childhood
      nephrotic syndrome, but has since been replaced by synthetic glucocorticoid
      analogues. In addition to controlling steroidogenesis, ACTH also acts as an
      important physiological agonist of the melanocortin system. Clinical and
      experimental evidence now suggests that ACTH has antiproteinuric, lipid-lowering
      and renoprotective properties, which are not fully explained by its steroidogenic
      effects. ACTH therapy is effective in inducing remission of nephrotic syndrome in
      patients with a variety of proteinuric nephropathies, even those resistant to
      steroids and other immunosuppressants. This Perspectives article describes the
      biophysiology of ACTH, with an emphasis on its melanocortin actions, particularly
      in renal parenchymal cells, which could potentially explain the therapeutic
      effects of ACTH in nephrotic glomerulopathies.

PMID- 22143336
TI  - Nasal irrigation with or without drugs:  the evidence.
AB  - PURPOSE OF REVIEW: To review the recent literature of nasal irrigations with or
      without drugs, including delivery systems, nasal saline, antibiotics,
      antifungals, steroids, surfactants, and interleukin (IL)-5 modulators, for the
      treatment of chronic rhinosinusitis (CRS). RECENT FINDINGS: As antibiotic
      resistance increases in CRS, culture-directed, rather than empiric, topical
      antibiotics are increasingly critical in optimal treatment. Topical irrigation
      with mupirocin significantly reduces Staphylococcus aureus biofilm mass in vitro.
      Surfactants and humanized anti-IL-5 monoclonal antibody are novel therapies
      demonstrating promising results in CRS. SUMMARY: Physiologic saline irrigation is
      beneficial in the treatment of symptoms of CRS. Low-level evidence supports the
      effectiveness of topical antibiotics in the treatment of CRS. The use of topical
      antifungals is not supported by the majority of studies. Intranasal steroids are
      beneficial in the treatment of CRS with nasal polyposis. There is insufficient
      evidence to demonstrate a clear overall benefit for topical steroids in CRS
      without nasal polyposis.

PMID- 22143337
TI  - Nasal septal perforation repair:  predictive factors and systematic review of the
      literature.
AB  - PURPOSE OF REVIEW: Although numerous surgical techniques have been introduced
      thus far in order to achieve the surgical closure of nasal septal perforation,
      the repair of nasal septal perforation is still challenging for surgeons and
      operative techniques are not standardized. Furthermore, predictive factors for
      successful closure have not been elucidated. This review aimed to investigate
      predictive factors for complete closure of nasal septal perforation. RECENT
      FINDINGS: The size of perforation was the most significant factor for complete
      closure. Surgical failure occurred more frequently in patients with large
      perforation (>2 cm) than those with small-to-moderate perforation (<=2 cm). The
      bilateral coverage over the perforation with vascularized mucosal flap also
      helped complete closure. Interposition of grafts appeared to assist complete
      closure, although it was statistically insignificant. SUMMARY: This review
      provides information for surgeons on how to predict surgical outcomes of the
      repair of nasal septal perforation and which surgical techniques to choose in
      order to obtain better results.

PMID- 22143339
TI  - Gustatory rhinitis.
AB  - PURPOSE OF REVIEW: This review aims to characterize gustatory rhinitis using
      recent advances in pathophysiology and novel surgical and medical management
      strategies. RECENT FINDINGS: A significant amount of research has recently
      focused on the role of capsaicin and its receptors (TRPV1 and VR1), which can be
      found on sensory c-fibers in human nasal mucosa and play a critical role in the
      development of nasal hyperresponsiveness to environmental factors. Blocking the
      nasal sensory nerve stimulation (via the use of capsaicin desensitization) or
      outgoing parasympathetic innervation (via endoscopic Vidian neurectomy) may
      control nasal hyperresponsiveness and therefore prevent the induction of rhinitis
      symptoms. SUMMARY: Gustatory rhinitis is a conspicuous type of food-associated
      rhinorrhea, which can occasionally be associated with significant quality-of-life
      impairment. It results from an abnormal gustatory reflex associated with a
      hyperactive, nonadrenergic, noncholinergic, or peptidergic neural system. The use
      of nasal ipratropium bromide may be effective, if avoidance is not possible or
      successful. We have had excellent results with the use of intranasal capsaicin or
      endoscopic vidian neurectomy (including removal of 4-5 mm of the nerve between
      pterygopalatine fossa and the sphenoid floor) in patients with nonallergic
      rhinitis, and these could potentially be used as a last resort in patients with
      intractable gustatory rhinitis.

PMID- 22143338
TI  - Olfactory improvement after endoscopic sinus surgery.
AB  - PURPOSE OF REVIEW: Olfactory dysfunction is a common complaint in patients with
      chronic rhinosinusitis (CRS). The purpose of this article is to review the
      current evidence on the impact of endoscopic sinus surgery (ESS) on CRS-related
      olfactory dysfunction. RECENT FINDINGS: The recent literature suggests that
      olfactory outcomes after ESS are challenging to predict. Some evidence supports a
      positive impact of ESS on improving olfactory outcomes in patients with
      preoperative nasal polyposis and anosmia. However, despite improvements in smell,
      most of these patients remain with severe hyposmia. One study suggests ESS has no
      impact on olfactory outcomes. SUMMARY: CRS-related olfactory dysfunction is a
      complex clinical scenario and it is challenging to predict improvement following
      ESS. CRS patients with anosmia and nasal polyposis preoperatively may have a
      higher likelihood of olfactory improvement following ESS.

PMID- 22143340
TI  - Aortitis in a patient with psoriatic arthritis.
AB  - Aortitis, inflammation of the aortic tissue, is most commonly caused by
      vasculitic rheumatic conditions, and less frequently infectious organisms.
      Involvement of the aorta is well defined in HLA-B27-associated
      spondyloarthropathies such as long-standing ankylosing spondylitis and Reiter's
      syndrome. However, unlike other spondyloarthropathies, aortic involvement or true
      aortitis is not a feature of psoriatic arthritis and has been reported in only a
      few cases. Herein, we report the case of a 22 year-old woman with psoriatic
      arthritis who developed descending aortitis while using tumor necrosis factor
      inhibitors.

PMID- 22143341
TI  - Clinicopathologic study of the MIB-1 labeling index (Ki67) and postoperative
      prognosis for intraductal papillary mucinous neoplasms and ordinary ductal
      adenocarcinoma.
AB  - OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are pathologically
      classified as IPMN with low- or intermediate-grade dysplasia, IPMN with high
      grade dysplasia, and IPMN with an associated invasive carcinoma. A stepwise
      carcinogenic pathway has been considered for IPMN. However, it is not obvious
      when surgical resection should be performed for IPMN. METHODS: We studied the MIB
      1 labeling index in cases of IPMN and ordinary ductal adenocarcinoma (ODA).
      Moreover, IPMN with an associated invasive carcinoma was divided into 2, namely,
      carcinoma in situ and invasive components, and the respective MIB-1 labeling
      indexes were examined. RESULTS: The MIB-1 labeling index for IPMN with low- or
      intermediate-grade dysplasia (1.8%) was significantly lower than those for IPMN
      with high-grade dysplasia (14.2%), both the carcinoma in situ components (23.1%)
      and invasive components (19.2%) within the IPMN with an associated invasive
      carcinoma, and ODA (19.5%; P < 0.0001).The 5-year survival rates after resection
      were 100% for IPMN with low- or intermediate-grade dysplasia, 83.3% for IPMN with
      high-grade dysplasia, 53.8% for IPMN with an associated invasive carcinoma, and
      10.3% for ODA. CONCLUSIONS: MIB-1 might be useful for the classification of
      malignant potential in IPMN. Intraductal papillary mucinous neoplasm should be
      surgically resected when the tumor is diagnosed as IPMN with high-grade
      dysplasia.

PMID- 22143343
TI  - Suppression of NANOG induces efficient differentiation of human embryonic stem
      cells to pancreatic endoderm.
AB  - OBJECTIVE: A challenge in using human embryonic stem cells (hESCs) as the source
      of surrogate beta cells is the establishment of methods that could effectively
      direct their differentiation into functional beta cells. The aim of this study
      was to assess the effect of NANOG gene suppression in differentiating hESCs as a
      mean of increasing the efficiency with which endoderm-derived pancreatic cells
      could be generated. METHODS: A homogenous cell population with stable suppression
      of NANOG was generated in hESC ENVY line using plasmid-based siRNA approach.
      Pancreatic differentiation was undertaken according to the ontology-based in
      vitro selection protocol and followed by transplantation into immunodeficiency
      mice to mature in vivo. RESULTS: We observed up-regulation of definitive endoderm
      genes, which expand the role of NANOG in blocking definitive endoderm
      differentiation. The ontology-based differentiation protocol resulted in
      increased expression of markers essential for pancreatic epithelium development.
      Transplantation of these cells further revealed a homogenous pancreatic exocrine
      like morphology that stained positively for amylase. CONCLUSIONS: The suppression
      of NANOG displayed an effective differentiation toward endoderm and pancreatic
      progenitors. Investigation of the factors required for endocrine formation
      combined with a prolonged in vivo culturing could be further used to increase the
      ratio of endocrine-exocrine cells fate.

PMID- 22143344
TI  - Ca(2+) channel currents of cortical neurons from pure and mixed cultures.
AB  - Voltage-gated Ca(2+) channels (VGCCs) are key regulators of many neuronal
      functions, and involved in multiple central nervous system diseases. In the last
      30 years, a large number of injury and disease models have been established based
      on cultured neurons. Culture with serum develops a mixture of neurons and glial
      cells, while culture without serum develops pure neurons. Both of these neuronal
      culture methods are widely used. However, the properties of Ca(2+) currents in
      neurons from these two cultures have not been compared. In this study, we
      cultured rat cortical neurons in serum-containing or -free medium and then
      recorded the Ca(2+) channel currents using patch-clamp technique. Our results
      showed that there were significant differences in the amplitude and activation
      properties of whole-cell Ca(2+) channel currents, and of non-L-type Ca(2+)
      channel currents between the neurons from these two culture systems. Our data
      suggested that the difference of whole-cell Ca(2+) currents may result from the
      differences in non-L-type currents. Understanding of these properties will
      considerably advance studies of VGCCs in neurons from pure or mixed culture.

PMID- 22143342
TI  - Characterization of a novel functional protein in the pancreatic islet: islet
      homeostasis protein regulation of glucagon synthesis in alpha cells.
AB  - OBJECTIVE: We have identified a novel protein in bone marrow-derived insulin
      producing cells. Here we characterize this protein, hereby named islet
      homeostasis protein (IHoP), in the pancreatic islet. METHODS: Detection of IHoP
      mRNA and protein was performed using reverse transcriptase-polymerase chain
      reaction, immunocytochemistry, and in situ hybridization. Islet homeostasis
      protein functions were utilizing proliferation, insulin secretion by in vitro
      assays, and following small interfering RNA protocols for suppression of IHoP.
      RESULTS: We found that IHoP did not homolog with known pancreatic hormones. Islet
      homeostasis protein expression was seen in both bone marrow-derived insulin
      producing cells and isolated pancreatic islets. Immunohistochemistry on
      pancreatic islet revealed that IHoP localized to the glucagon-synthesizing alpha
      cells. Inhibition of IHoP by small interfering RNA resulted in the loss of
      glucagon expression, which induced low blood glucose levels (63-85 mg/dL).
      Subsequently, cellular apoptosis was observed throughout the islet, including the
      insulin-producing beta cells. Islets of preonset diabetic patients showed normal
      expression of IHoP and glucagon; however, IHoP was lost upon onset of the
      disease. CONCLUSIONS: These data suggest that IHoP could be a new functional
      protein in the islet and may play a role in islet homeostasis.

PMID- 22143345
TI  - Suppressive effects of natural reduced waters on alloxan-induced apoptosis and
      type 1 diabetes mellitus.
AB  - Insulin-producing cells express limited activities of anti-oxidative enzymes.
      Therefore, reactive oxygen species (ROS) produced in these cells play a crucial
      role in cytotoxic effects. Furthermore, diabetes mellitus (DM) development is
      closely linked to higher ROS levels in insulin-producing cells. Hita Tenryosui
      Water((r)) (Hita T. W., Hita, Japan) and Nordenau water (Nord. W., Nordenau,
      Germany), referred to as natural reduced waters (NRWs), scavenge ROS in cultured
      cells, and therefore, might be a possibility as an alternative to conventional
      pharmacological agents against DM. Therefore, this study aimed to investigate the
      role of NRWs in alloxan (ALX)-induced beta-cell apoptosis as well as in ALX
      induced diabetic mice. NRWs equally suppressed DNA fragmentation levels. Hita T.
      W. and Nord. W. ameliorated ALX-induced sub-G(1) phase production from
      approximately 40% of control levels to 8.5 and 11.8%, respectively. NRWs restored
      serum insulin levels (p < 0.01) and reduced blood glucose levels (p < 0.01) in
      ALX-induced mice. Hita T. W. restored tissue superoxide dismutase (SOD) (p <
      0.05) activity but not tissue catalase activity. Hita T. W. did not elevate SOD
      or catalase activity in HIT-T15 cells. Nord. W. restored SOD (p < 0.05) and
      catalase (p < 0.05) activity in both cultured cells and pancreatic tissue to
      normal levels. Even though variable efficacies were observed between Hita T. W.
      and Nord. W., both waters suppressed ALX-induced DM development in CD-1 male mice
      by administering NRWs for 8 weeks. Our results suggest that Hita T. W. and Nord.
      W. protect against ALX-induced beta-cell apoptosis, and prevent the development
      of ALX-induced DM in experimental animals by regulating ALX-derived ROS
      generation and elevating anti-oxidative enzymes. Therefore, the two NRWs tested
      here are promising candidates for the prevention of DM development.

PMID- 22143346
TI  - Directed cellular self-assembly to fabricate cell-derived tissue rings for
      biomechanical analysis and tissue engineering.
AB  - Each year, hundreds of thousands of patients undergo coronary artery bypass
      surgery in the United States.(1) Approximately one third of these patients do not
      have suitable autologous donor vessels due to disease progression or previous
      harvest.  The aim of vascular tissue engineering is to develop a suitable
      alternative source for these bypass grafts.  In addition, engineered vascular
      tissue may prove valuable as living vascular models to study cardiovascular
      diseases.  Several promising approaches to engineering blood vessels have been
      explored, with many recent studies focusing on development and analysis of cell
      based methods.(2-5)  Herein, we present a method to rapidly self-assemble cells
      into 3D tissue rings that can be used in vitro to model vascular tissues. To do
      this, suspensions of smooth muscle cells are seeded into round-bottomed annular
      agarose wells.  The non-adhesive properties of the agarose allow the cells to
      settle, aggregate and contract around a post at the center of the well to form a
      cohesive tissue ring.(6,7)  These rings can be cultured for several days prior to
      harvesting for mechanical, physiological, biochemical, or histological analysis. 
      We have shown that these cell-derived tissue rings yield at 100-500 kPa ultimate
      tensile strength(8) which exceeds the value reported for other tissue engineered
      vascular constructs cultured for similar durations (<30 kPa).(9,10)  Our results
      demonstrate that robust cell-derived vascular tissue ring generation can be
      achieved within a short time period, and offers the opportunity for direct and
      quantitative assessment of the contributions of cells and cell-derived matrix
      (CDM) to vascular tissue structure and function.

PMID- 22143347
TI  - Synthesis of heparin oligosaccharides and their interaction with eosinophil
      derived neurotoxin.
AB  - A convenient route for the synthesis of heparin oligosaccharides involving
      regioselective protection of D-glucosamine and a concise preparation of rare L
      ido sugars from diacetone alpha-D-glucose is described. Stereoselective coupling
      of a D-glucosamine-derived trichloroacetimidate with a 1,6-anhydro-beta-L
      idopyranosyl 4-alcohol gave the desired alpha-linked disaccharide, which was used
      as repeating unit for dual chain elongation and termination. Stepwise assembly
      from the reducing to the non-reducing end with a D-glucosamine-derived
      monosaccharide as starting unit furnished the oligosaccharide skeletons having
      different chain lengths. A series of functional group transformations afforded
      the expected heparin oligosaccharides with 3, 5 and 7 sugar units. Interaction of
      these oligosaccharides with eosinophil-derived neurotoxin (EDN), a cationic
      ribonuclease and a mediator produced by human eosinophils, was further
      investigated. The results revealed that at 5 MUg mL(-1), the heptasaccharide has
      sufficiently strong interference to block EDN binding to Beas-2B cells. The tri-
      and pentasaccharides have moderate inhibitory properties at 50 MUg mL(-1)
      concentration, but no inhibition has been observed at 10 MUg mL(-1). The IC(50)
      values of the tri-, penta- and heptasaccharides are 69.4, 47.2 and 0.225 MUg mL(
      1), respectively.

PMID- 22143350
TI  - Terminal 14q deletion with unbalanced t(Y;14)(q12;q32) translocation.
AB  - Terminal deletions of chromosome 14q are very rarely reported. Schneider et al.
      (2008) reviewed about 20 cases of 14q32 region deletion in a previous article and
      only three of the cases involved autosomal translocations; however, no sex
      chromosome translocations were reported. Here we report the clinical findings of
      a patient with terminal 14q32 deletion derivated from at (Y;14)(q12;q32)
      translocation.

PMID- 22143348
TI  - Study of inferior dental canal and its contents using high-resolution magnetic
      resonance imaging.
AB  - The aim of this study was to evaluate the visualizability, topography, and course
      of the mandibular canal with particular attention to the incisive canal on 3-T
      MRI. Particular attention was paid to the incisive canal anastomosis at the
      symphysis. A total of 64 dentate patients were examined using a modified T2 space
      sequence using 3-T MRI. The scans were analyzed with respect to the topography of
      the entire course of the mandibular canal, mental canal, incisive canal, and
      nutrient canals. The high-field MRI of the lower jaw allowed detailed
      visualization of the mandibular canal, the incisive canal, and the surrounding
      connective tissue structures. In the context of the present study, 3-T MRI was
      found to be a potentially useful imaging method for displaying the course of the
      entire inferior dental canal for pre-implantation planning, surgical planning,
      and diagnosis.

PMID- 22143351
TI  - 14q32 deletion syndrome:  a clinical report.

PMID- 22143352
TI  - Robust antimicrobial compounds and polymers derived from natural resin acids.
AB  - We report novel robust resin acid-derived antimicrobial agents that exhibit
      excellent antimicrobial activities against a broad spectrum of bacteria (6 Gram
      positive and 7 Gram-negative) with selective lysis of microbial membranes over
      mammalian membranes. Our results indicate that hydrophobicity and unique
      structures of resin acids can be determining factors in dictating the
      antimicrobial activity.

PMID- 22143353
TI  - Lexical and prosodic effects on syntactic ambiguity resolution in aphasia.
AB  - The purpose of this study was to determine whether and when individuals with
      aphasia and healthy controls use lexical and prosodic information during on-line
      sentence comprehension. Individuals with aphasia and controls (n = 12 per group)
      participated in a self-paced listening experiment. The stimuli were early closure
      sentences, such as "While the parents watched(,) the child sang a song." Both
      lexical and prosodic cues were manipulated. The cues were biased toward the
      subject- or object- of the ambiguous noun phrase (the child). Thus, there were
      two congruous conditions (in which both lexical cues and prosodic cues were
      consistent) and two incongruous conditions (in which lexical and prosodic cues
      conflicted). The results showed that the people with aphasia had longer listening
      times for the ambiguous noun phrase (the child) when the cues were conflicting,
      rather than consistent. The controls showed effects earlier in the sentence, at
      the subordinate verb (watched or danced). Both groups showed evidence of
      reanalysis at the main verb (sang). These effects demonstrate that the aphasic
      group was sensitive to the lexical and prosodic cues, but used them on a delayed
      time course relative to the control group.

PMID- 22143355
TI  - Role of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA in
      intrahepatic cholangiocarcinoma.
AB  - PURPOSE: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are
      important enzymes in the metabolism of 5-fluorouracil and possible predictive
      markers. We conducted this study to clarify if TS and DPD gene expressions are a
      prognostic indicator for intrahepatic cholangiocarcinoma (IHCC). METHODS: The
      subjects of this study were 21 patients with IHCC who had undergone surgical
      resection. Intratumoral TS and DPD mRNA expressions were examined using the
      Danenberg tumor profile method and classified into two groups according to the
      median value of each. We then compared the clinicopathological variables,
      including prognosis, between the high and low expression groups. RESULTS: Low DPD
      expression was correlated with macroscopic type, namely, mass-forming +
      infiltrative (P = 0.08). Postoperative survival rates in the low DPD expression
      group were significantly lower than those in the high DPD expression group.
      Multivariate analysis revealed macroscopic type to be an independent prognostic
      factor, whereas TS mRNA expression did not correlate with any clinicopathological
      variables, including prognosis. CONCLUSIONS: Low DPD mRNA expression was related
      to macroscopic type and associated with poor prognosis. DPD mRNA expression in
      tumor cells is suggested to be an important regulator of malignant behavior in
      IHCC.

PMID- 22143357
TI  - Yellow nail syndrome with thoracic empyema: report of a case.
AB  - We report a rare case of yellow nail syndrome (YNS) complicated by thoracic
      empyema. The patient was a 75-year-old man with yellow nails and a history of
      respiratory illnesses. Initially he presented with recurrent pleural effusion,
      which developed into empyema within 3 years. This case serves to reinforce that
      recurrent pleural effusions should be initiated in the early stage of YNS to
      prevent the development of empyema.

PMID- 22143356
TI  - Relationship between expression of apoptosis-related proteins and the efficacy of
      postoperative chemotherapy in patients with T3 gastric cancer.
AB  - PURPOSE: We investigated the relationship between the p53-dependent apoptotic
      pathway and the survival of patients with gastric cancer, retrospectively, to
      elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy. METHODS: We
      examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1)
      proteins immunohistochemically in 105 patients who underwent curative gastrectomy
      for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for
      1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank
      test. RESULTS: Positive staining for p53, p21, Bax, and Mcl-1 proteins was found
      in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did
      not differ significantly between the patients with and those without p53, p21,
      and Bax expression. However, patients with Mcl-1- tumors survived longer than
      those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival;
      however, adjuvant UFT significantly prolonged the survival of patients with p53-,
      p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl
      1- tumors. CONCLUSIONS: The efficacy of adjuvant chemotherapy for gastric cancer
      may be affected by the status of apoptosis-related proteins such as p53, p21,
      Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the
      sensitivity of chemotherapeutic agents, further investigation of the mutual
      interaction between apoptosis-related proteins is required.

PMID- 22143354
TI  - Perspectives of purinergic signaling in stem cell differentiation and tissue
      regeneration.
AB  - Replacement of lost or dysfunctional tissues by stem cells has recently raised
      many investigations on therapeutic applications. Purinergic signaling has been
      shown to regulate proliferation, differentiation, cell death, and successful
      engraftment of stem cells originated from diverse origins. Adenosine triphosphate
      release occurs in a controlled way by exocytosis, transporters, and lysosomes or
      in large amounts from damaged cells, which is then subsequently degraded into
      adenosine. Paracrine and autocrine mechanisms induced by immune responses present
      critical factors for the success of stem cell therapy. While P1 receptors
      generally exert beneficial effects including anti-inflammatory activity, P2
      receptor-mediated actions depend on the subtype of stimulated receptors and
      localization of tissue repair. Pro-inflammatory actions and excitatory tissue
      damages mainly result from P2X7 receptor activation, while other purinergic
      receptor subtypes participate in proliferation and differentiation, thereby
      providing adequate niches for stem cell engraftment and novel mechanisms for cell
      therapy and endogenous tissue repair. Therapeutic applications based on
      regulation of purinergic signaling are foreseen for kidney and heart muscle
      regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial
      cells as well as for induction of neurogenesis in case of neurodegenerative
      diseases.

PMID- 22143358
TI  - Effectiveness of muscle coverage to manage osteomyelitis of very late onset in
      the irradiated chest wall.
AB  - Radiation therapy for breast cancer has improved survival rates; however, a
      consequence of this is treatment-induced complications in longer-living patients.
      Decades after chest wall irradiation, very late onset radiation-induced
      osteomyelitis can develop, caused by osteoradionecrosis. This may lead to the
      development of small, but very refractory, skin ulcers. Many reports recommend
      well-vascularized tissue coverage after appropriate debridement for irradiation
      ulcers; however, when the ulcers are of very late onset, this sometimes causes
      recurrence of ulceration in non-muscle-covered areas after flap transfer. Thus,
      for very late onset cases, we propose treatment with an absolute muscle flap to
      cover both the obviously infected focus and the surrounding irradiated area. A
      muscle flap consisting of the entire latissimus dorsi, the shape of which is very
      large in the horizontal direction, satisfies this requirement. Latissimus dorsi
      muscle coverage for the treatment of very late onset osteomyelitis should be
      reappraised.

PMID- 22143359
TI  - Intra-hepatic arterioportal shunt mimicking a metastatic liver tumor: report of a
      case.
AB  - The differential diagnosis of an arterioportal shunt (APS) is difficult and
      important. We report a case of an intra-hepatic APS mimicking a metastatic liver
      tumor on imaging scans in a patient without hepatic cirrhosis. The patient was a
      64-year-old woman, who had undergone low anterior resection of the rectum for
      advanced rectal cancer, followed 2 months later by right hemihepatectomy,
      including the middle hepatic vein, for a synchronous metastatic liver tumor.
      About 2 years after the hepatectomy, a follow-up CT scan showed a new mass in the
      remnant liver, suggestive of a metastatic liver tumor, the assumption of which
      was further supported by an elevated serum carcinoembryonic antigen (CEA) level.
      However, the findings of magnetic resonance imaging were not consistent with a
      malignant tumor, and Doppler ultrasonography showed a low echoic area connected
      with the portal vein branch and the hepatic artery branch. Thus, we diagnosed
      intra-hepatic APS. The patient remains well without signs of growth of the
      hepatic lesion, although with fluctuating serum CEA levels.

PMID- 22143360
TI  - Organisational determinants of production and efficiency in general practice: a
      population-based study.
AB  - OBJECTIVE: Shortage of general practitioners (GPs) and an increased political
      focus on primary care have enforced the interest in efficiency analysis in the
      Danish primary care sector. This paper assesses the association between
      organisational factors of general practices and production and efficiency.
      METHODS: We assume that production and efficiency can be modelled using a
      behavioural production function. We apply the Battese and Coelli (Empir Econ
      20:325-332, 1995) estimator to accomplish a decomposition of exogenous variables
      to determine the production frontier and variables determining the individual GPs
      distance to this frontier. Two different measures of practice outputs (number of
      office visits and total production) were applied and the results compared.
      RESULTS: The results indicate that nurses do not substitute GPs in the
      production. The production function exhibited constant returns to scale. The mean
      level of efficiency was between 0.79 and 0.84, and list size was the most
      important determinant of variation in efficiency levels. CONCLUSIONS: Nurses are
      currently undertaking other tasks than GPs, and larger practices do not lead to
      increased production per GP. However, a relative increase in list size increased
      the efficiency. This indicates that organisational changes aiming to increase
      capacity in general practice should be carefully designed and tested.

PMID- 22143361
TI  - Alzheimer disease: AD pathology--emerging subtypes or age-of-onset spectrum?

PMID- 22143363
TI  - Imaging: Safety of spinal angiography.

PMID- 22143362
TI  - MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials.
AB  - Over the past 15 years, MRI lesion activity has become the accepted surrogate
      primary outcome measure in proof-of-concept placebo-controlled clinical trials of
      new immunomodulating therapies in relapse-onset multiple sclerosis (MS). In
      parallel, the number of patients that are available for the placebo arm of trials
      has declined, and more-aggressive drugs are being developed. A critical review is
      warranted to ensure efficient MRI--and patient--resource utilization. Recently,
      an international panel reviewed the methodology for efficient use of MRI
      monitored trials in relapse-onset MS. In this article, we provide up-to-date
      recommendations for scan acquisition, image analysis, outcome-measure definition
      and standards of reporting. Factors to consider for optimizing trial design, such
      as outcome measure selection and the unique requirements of phase II and phase
      III trials, including active-comparator studies, are outlined. Finally, we
      address safety considerations in the use of MRI in MS trials, and the safety
      related responsibilities of the various parties involved in conducting such
      trials.

PMID- 22143365
TI  - Parkinson disease: Twin study identifies an association between exposure to a
      solvent and risk of Parkinson disease.

PMID- 22143364
TI  - Postural tachycardia syndrome--current experience and concepts.
AB  - Postural tachycardia syndrome (PoTS) is a poorly understood but important cause
      of orthostatic intolerance resulting from cardiovascular autonomic dysfunction.
      PoTS is distinct from the syndromes of autonomic failure usually associated with
      orthostatic hypotension, such as pure autonomic failure and multiple system
      atrophy. Individuals affected by PoTS are mainly young (aged between 15 years and
      40 years) and predominantly female. The symptoms--palpitations, dizziness and
      occasionally syncope--mainly occur when the patient is standing upright, and are
      often relieved by sitting or lying flat. Common stimuli in daily life, such as
      modest exertion, food ingestion and heat, are now recognized to be capable of
      exacerbating the symptoms. Onset of the syndrome can be linked to infection,
      trauma, surgery or stress. PoTS can be associated with various other disorders;
      in particular, joint hypermobility syndrome (also known as Ehlers-Danlos syndrome
      hypermobility type, formerly termed Ehlers-Danlos syndrome type III). This Review
      describes the characteristics and neuroepidemiology of PoTS, and outlines
      possible pathophysiological mechanisms of this syndrome, as well as current and
      investigational treatments.

PMID- 22143366
TI  - Motor neuron disease: Functional screening identifies novel candidate risk genes
      in amyotrophic lateral sclerosis.

PMID- 22143371
TI  - Multidisciplinary treatment of malignant thymoma.
AB  - PURPOSE OF REVIEW: Thymomas are the most common tumors of the anterior
      mediastinum. Although surgery remains the only curative treatment, the use of
      multimodality therapy for primary unresectable thymomas has led to change the
      clinical management of these tumors. RECENT FINDINGS: Nowadays Masaoka stage,
      WHO, and radical surgical resection are considered by many authors as independent
      prognostic factors for long-term survival. Radiotherapy may be useful as adjuvant
      therapy in cases of incomplete surgical resection with microscopic or macroscopic
      residual disease, or for those patients with locally advanced or metastatic
      unresectable disease. Chemotherapy is considered a valid option in selected
      patients with residual disease after local treatments or as a neoadjuvant
      approach to improve resectability in Masaoka stages III or IV-a thymomas.
      Currently, no standardized regimen for chemotherapy or agreed timing exists.
      SUMMARY: So far, multimodality treatment has been related to low morbidity and
      long survival rate, but there are still many concerns regarding a different
      regimen of therapy and the correct timing.

PMID- 22143370
TI  - Cancer as a metabolic disease.

PMID- 22143367
TI  - Epithelial expression of vasoactive intestinal peptide in ulcerative colitis:
      down-regulation in markedly inflamed colon.
AB  - BACKGROUND: Vasoactive intestinal peptide (VIP) has a number of important effects
      in intestinal physiology and pathology, including in ulcerative colitis (UC). The
      expression patterns of the predominant VIP receptor in the mucosa (the VPAC1
      receptor) are unknown for the mucosa in UC. It is assumed that the sources of VIP
      in the intestine are the innervation and the inflammatory cells. AIMS: The VIP
      and VPAC1 receptor expression patterns in the epithelial layer of UC and non-UC
      patients were examined in the present study. The influence of marked inflammation
      of the mucosa was evaluated. METHODS: Specimens of the human colon, including the
      colon of UC patients, were examined concerning expressions of VIP and VPAC1
      receptor, focusing on the epithelial layer. Immunohistochemistry and in situ
      hybridization were utilized. RESULTS: There were VIP mRNA reactions and also
      marked VPAC1 receptor immunoreactions in the normal and slightly/moderately
      affected epithelium. VIP mRNA reactions were not detected and VPAC1
      immunoreactions were minimal in response to marked mucosal derangement.
      CONCLUSIONS: The findings suggest that there is a local production of VIP in the
      epithelial cells in normal and slightly/moderately inflamed mucosa but not in
      severely inflamed mucosa. Furthermore, a marked downregulation in VPAC1 receptor
      expressions occurs in the epithelium in severe UC. Based on the knowledge that
      VIP can have trophic, healing and anti-inflammatory effects, it is likely that
      the decrease in VIP mRNA and VPAC1 receptor reactions seen in severely affected
      mucosa in UC may be associated with adverse effects on intestinal function.

PMID- 22143368
TI  - Meta-analysis: the impact of nutritional status on the immune response to
      hepatitis B virus vaccine in chronic kidney disease.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) typically show a
      diminished immune response to hepatitis B virus (HBV) vaccine compared with
      individuals with intact kidney function. A number of inherited or acquired
      factors have been implicated in this suboptimal response. Patients with chronic
      kidney disease frequently have a compromised nutritional status; however, the
      impact of malnutrition on the immune response to hepatitis B virus vaccine in
      chronic kidney disease patients remains unclear. AIM: To evaluate the influence
      of nutrition status on the immune response to HBV vaccine in CKD population by
      performing a systematic review of the literature with a meta-analysis of clinical
      studies. METHODS: Study-specific relative risks were weighted by the inverse of
      their variance to obtain fixed- and random-effects pooled estimates of impaired
      vaccine response across the published studies. The risk of poor serological
      response to HBV vaccine in chronic kidney disease population according to
      nutritional parameters was regarded as the most reliable outcome end-point. Only
      studies performing multivariate analysis in order to make adjustments for
      potential confounders were included. RESULTS: We identified seven studies (15,172
      unique patients with CKD). The serum protection rate after a full course of
      recombinant or plasma-derived vaccine towards HBV ranged between 40 and 86%.
      Aggregation of study results showed an independent and adverse effect of poor
      nutrition status, as mostly detected by serum albumin levels, on the protection
      rate after HBV vaccine course; the summary estimate for adjusted RR was 1.50 with
      a 95% confidence interval (CI) of 1.02, 2.21; R( i ) = 0.01 (random-effects
      model). The P value for study heterogeneity was significant (Q = 0.0001). In the
      subgroup of patients who received HBV recombinant vaccine, the relative risk of
      impaired serological response after HBV vaccination was 1.63 (95% CI, 1.08,
      2.45), R( i ) = 0.90, Q = 0.00001, with poor nutritional parameters at baseline.
      CONCLUSIONS: An increased risk exists of impaired serologic response to HBV
      vaccine response among chronic kidney disease patients having poor nutrition
      status. Additional studies are needed to understand better the mechanisms
      underlying the relationship between nutritional status and serological response
      to HBV vaccine among patients with CKD.

PMID- 22143372
TI  - Electroporation of craniofacial mesenchyme.
AB  - Electroporation is an efficient method of delivering DNA and other charged
      macromolecules into tissues at precise time points and in precise locations. For
      example, electroporation has been used with great success to study neural and
      retinal development in Xenopus, chicken and mouse (1-10). However, it is
      important to note that in all of these studies, investigators were not targeting
      soft tissues. Because we are interested in craniofacial development, we adapted a
      method to target facial mesenchyme. When we searched the literature, we found, to
      our surprise, very few reports of successful gene transfer into cartilaginous
      tissue. The majority of these studies were gene therapy studies, such as siRNA or
      protein delivery into chondrogenic cell lines, or, animal models of arthritis (11
      13). In other systems, such as chicken or mouse, electroporation of facial
      mesenchyme has been challenging (personal communications, Dept of Craniofacial
      Development, KCL). We hypothesized that electroporation into procartilaginous and
      cartilaginous tissues in Xenopus might work better. In our studies, we show that
      gene transfer into the facial cartilages occurs efficiently at early stages (28),
      when the facial primordium is still comprised of soft tissue prior to cartilage
      differentiation. Xenopus is a very accessible vertebrate system for analysis of
      craniofacial development. Craniofacial structures are more readily visible in
      Xenopus than in any other vertebrate model, primarily because Xenopus embryos are
      fertilized externally, allowing analyses of the earliest stages, and facilitating
      live imaging at single cell resolution, as well as reuse of the mothers (14).
      Among vertebrate models developing externally, Xenopus is more useful for
      craniofacial analysis than zebrafish, as Xenopus larvae are larger and easier to
      dissect, and the developing facial region is more accessible to imaging than the
      equivalent region in fish. In addition, Xenopus is evolutionarily closer to
      humans than zebrafish (~100 million years closer) (15). Finally, at these stages,
      Xenopus tadpoles are transparent, and concurrent expression of fluorescent
      proteins or molecules will allow easy visualization of the developing cartilages.
      We anticipate that this approach will allow us to rapidly and efficiently test
      candidate molecules in an in vivo model system.

PMID- 22143373
TI  - Carbon assimilation and digestive toxicity in naive grass shrimp (Palaemonetes
      pugio) exposed to dietary cadmium.
AB  - Naive grass shrimp Palaemonetes pugio were pulse-fed cadmium-contaminated meals
      containing carbon-14, fluorescent or near-infrared markers and analyzed for
      carbon assimilation efficiency, gut residence time, feces elimination rate,
      extracellular digestive protease activity or gut pH. Carbon assimilation
      efficiency (~83%), minimum gut residence time (~435 min) and proventriculus pH
      (~5.29 to ~6.01) were not impacted significantly by cadmium ingestion. A dose
      dependent decrease in feces elimination rate (from ~14.4 to ~6.4 mm h(-1)) was
      observed for shrimp for 2 h following minimum gut residence time. Protease
      activities increased ~2.4-fold over the range of dietary cadmium exposures,
      however, this variation was not dose-dependent. Differential impacts of cadmium
      exposure on carbon and cadmium assimilation reported previously are consistent
      with work involving shrimp subjected to chronic field exposure. The influence of
      ingested cadmium on feces elimination rate may be related to pre-assimilatory
      impacts on packaging, intestinal transport or release of feces. Protease
      activities may have been influenced by pre-assimilatory interactions between
      available cadmium ions in gut fluid and enzyme-secreting cells of the
      hepatopancreatic epithelium or direct impacts on active enzymes.

PMID- 22143375
TI  - Catalyst-free synthesis of iodine-doped graphene via a facile thermal annealing
      process and its use for electrocatalytic oxygen reduction in an alkaline medium.
AB  - Iodine-doped graphene has been successfully fabricated through a simple,
      economical, and scalable approach. The new metal-free catalyst can exhibit a high
      catalytic activity, long-term stability, and an excellent methanol tolerance for
      the oxygen reduction reaction.

PMID- 22143374
TI  - Cytoprotective effects of curcumin on sodium fluoride-induced intoxication in rat
      erythrocytes.
AB  - Curcumin is well known for its potent antioxidant activity. The result of
      numerous studies showed that antioxidants can protect against fluoride-induced
      toxicity. In the present study, protective effects of curcumin against sodium
      fluoride-induced toxicity in rat erythrocytes were evaluated. Curcumin (10 and 20
      mg/kg) and vitamin C (10 mg/kg) were administrated intraperitoneally for 1 week
      followed by sodium fluoride (600 ppm) treatment for next week. Erythrocytes were
      isolated and superoxide dismutase and catalase activities as well as the levels
      of reduced glutathione, and lipid peroxidation were measured. The level of
      malondialdehyde in sodium fluoride treated rats (595.13 +/- 20.23 nmol/g Hb)
      increased compared to the normal rats (315.44 +/- 9.76 nmol/g Hb). Animals which
      were pretreated with curcumin at 20 mg/kg for 1 week prior to sodium fluoride
      intoxication showed significant reduction in the malondialdehyde level (320.22 +/
      9.28 nmol/g Hb). Also, pretreated with curcumin (20 mg/kg) and vitamin C
      restored the superoxide dismutase and catalase activities and modified the level
      of reduced glutathione compared with control group (p > 0.01).

PMID- 22143376
TI  - Short-RNA selective binding of oligonucleotides modified using adenosine and
      guanosine derivatives that possess cyclohexyl phosphates as substituents.
AB  - We have developed new artificial oligonucleotides which distinguish short RNA
      targets from long ones. The modification of the 5' termini of oligonucleotides by
      using adenosine derivatives that possess a bulky cyclohexyl phosphate moiety at
      their base moiety and a phosphate group at the position of their 5'-hydroxyl
      group maximized their short RNA selectivity. The 2'-O-methyl-RNA (5'
      XC(m)A(m)A(m)C(m)C(m)U(m)A(m)C(m)U(m)) having these modifications exhibits ca. 10
      degrees C higher T(m) in the duplexes with the complementary short RNA (3'
      GUUGGAUGA-5') than with the long RNA (3'-AUUAUAUGUUGGAUGAUGGUUA-5'). The
      oligodeoxynucleotides having the same modification exhibited similar selectivity.
      Such short-RNA selective binding of terminally modified oligonucleotides can be
      employed to distinguish between mature microRNAs and pre-microRNAs.

PMID- 22143379
TI  - Treatment of experimental extravasation of amrubicin, liposomal doxorubicin, and
      mitoxantrone with dexrazoxane.
AB  - PURPOSE: Dexrazoxane is an established treatment option in extravasation of the
      classic anthracyclines such as doxorubicin, epirubicin, and daunorubicin.
      However, it is not known whether the protection against the devastating tissue
      injuries extends into extravasation with new types of anthracyclines, the
      anthracenediones, or the liposomal pegylated anthracycline formulations. We
      therefore tested the antidotal efficacy of dexrazoxane against extravasation of
      amrubicin, mitoxantrone, and liposomal pegylated doxorubicin in mice. METHODS: A
      total of 80 female B6D2F1 mice were tested in an established mouse extravasation
      model. The mice had experimental extravasations of amrubicin, mitoxtanrone, and
      Caelyx and were immediately hereafter treated with systemic dexrazoxane or
      saline. RESULTS AND CONCLUSION: Systemic treatment with dexrazoxane resulted in
      significant protection against extravasation injuries from all three drugs.
      Moreover, the vesicant potential of the three test drugs was weaker than seen in
      previous experiments with the classic anthracyclines.

PMID- 22143378
TI  - Phase I study for ridaforolimus, an oral mTOR inhibitor, in Japanese patients
      with advanced solid tumors.
AB  - PURPOSE: Ridaforolimus is a non-prodrug mTOR inhibitor. The safety,
      pharmacokinetics (PK), and antitumor activity of oral ridaforolimus were assessed
      in Japanese patients with refractory solid tumors. METHODS: Ridaforolimus (20 or
      40 mg) was administered as a single dose on Day 1, followed by once daily dosing
      five times a week for a 3-week cycle beginning on Day 8. Full PK sampling was
      performed on Days 1 and 26. RESULTS: Thirteen patients (7 at 20 mg and 6 at 40
      mg) were enrolled. The median treatment duration was 82 days. The most common
      drug-related adverse events were stomatitis, hypertriglyceridemia, and
      proteinuria. Two patients had dose-limiting toxicities (grade 3 stomatitis at 20
      mg, and grade 3 anorexia and vomiting at 40 mg). Four patients had grade 1
      interstitial pneumonitis. Ridaforolimus in the whole blood was rapidly absorbed
      and slowly eliminated with a half-life of approximately 56-58 h after a single
      dose. Two patients (with non-small cell lung cancer and angiosarcoma,
      respectively) achieved a partial response, and five patients (one with thymic
      cancer and four with soft tissue sarcomas) had a stable disease for >= 16 weeks.
      CONCLUSIONS: Ridaforolimus was well tolerated up to a dose of 40 mg in Japanese
      patients. Preliminary evidence of antitumor activity was observed for patients
      with solid tumors. Further investigation at this dose is warranted.

PMID- 22143381
TI  - Symptomatic and asymptomatic apical periodontitis associated with red complex
      bacteria: clinical and microbiological evaluation.
AB  - In this study, the association of red complex (RC) bacteria that include
      Treponema denticola, Tannerella forsythia and Porphyromonas gingivalis with
      acute, exacerbated or chronic apical periodontitis was evaluated. Seventy-one
      patients with periapical disease were evaluated by clinical examination and
      microbiological samples obtained from the root canals were analyzed by a
      polymerase chain reaction assay. Twenty-one (29.6%) samples were positive for RC
      bacteria, with T. denticola, T. forsythia and P. gingivalis being detected in 14
      (19.7%), 10 (14.1%) and 6 (8.5%) samples, respectively. RC bacteria were mainly
      associated with acute apical periodontitis (29.2%) and phoenix abscess (63.2%),
      while they were only sporadically detected (7.1%) in patients with chronic apical
      periodontitis. Generally, RC bacteria were associated with pain and a higher
      frequency of intracanalar/intrasulcular pus drainage. Involvement of RC bacteria
      in symptomatic periapical disease should be suspected in the presence of
      particularly severe clinical pain and pus drainage.

PMID- 22143382
TI  - Immobilization-free screening of aptamers assisted by graphene oxide.
AB  - Graphene oxide (GO) has the ability to separate free short ssDNA in heterogeneous
      solution. This feature is applied as a label free platform for screening of
      aptamers that bind to their target with high affinity and specificity. Herein, we
      report an aptamer selection strategy for Nampt protein based on GO.

PMID- 22143383
TI  - Colorimetric detection of apoptosis based on caspase-3 activity assay using
      unmodified gold nanoparticles.
AB  - A new label-free method for the detection of apoptosis was proposed based on
      colorimetric assay of caspase-3 activity using an unlabeled Asp-Glu-Val-Asp
      (DEVD)-containing peptide substrate and unmodified gold nanoparticles (AuNPs).

PMID- 22143385
TI  - Osteoarthritis: Complement-mediated inflammation in OA progression.

PMID- 22143386
TI  - Bone: a new angle on the relationship between DISH and AS.

PMID- 22143387
TI  - Connective tissue diseases: VSMC contraction in Systemic sclerosis.

PMID- 22143384
TI  - Responses of CYP450 dependent system to aliphatic and aromatic hydrocarbons body
      burden in transplanted mussels from South coast of Portugal.
AB  - Mussels Mytilus galloprovincialis were cross-transplanted at South Portugal from
      a reference site (site 1) to a site more contaminated with hydrocarbon compounds
      (site 2), and vice versa, in an active biomonitoring (ABM) concept, to assess the
      biotransformation capacity catalyzed by the mixed function oxygenase (MFO)
      system. Total alkanes (TAlk), the unresolved complex mixture (UCM), and total
      polycyclic aromatic hydrocarbons (TPAHs) concentration increased respectively 6,
      4.4 and 4.2 fold relatively to control, in mussels transplanted from site 1 to 2.
      In the cross-transplant, a 48, 57 and 62% depuration of TAlk, UCM and TPAHs
      concentrations occurred by the end of the 3-4th week. Petrogenic and biogenic
      (marine and terrigenous) sources of AHs, and petrogenic and pyrolitic (biomass
      and oil/fuel incomplete combustion) sources of PAHs were detected at both sites.
      CYP450, CYT b (5) and NADPH-RED in mussels transplanted from site 1 to 2 were
      induced from day 0 to 28, with a total increase of 35, 32 and 35%, respectively,
      while biochemical equilibrium to lesser environmental contamination occurs in
      mussels transplanted from site 2 to 1. A significant relationship between CYP450
      and NADPH-RED was found with TPAH, with distinctive behavior at the two sites.
      MFO system components increase with exposure time at one site and decreases in
      the other, reflecting an adaptation to distinct environmental hydrocarbon loads.
      The ABM strategy proved to be useful to understand the environment real impact on
      the biochemical responses in mussels' local populations. In this study, CYP450
      and NADPH-RED are a useful biomarker for hydrocarbon exposure.

PMID- 22143388
TI  - Bone: Effects of bisphosphonates on bone quality components and fracture risk.

PMID- 22143389
TI  - Screening: Guidelines for antiphospholipid antibody detection.

PMID- 22143390
TI  - Vasculitis syndromes: Peripheral neuropathy in AAV--when vasculitis hits a nerve.

PMID- 22143393
TI  - Nobel Prize laureates pave the way for therapeutic advances in sepsis.

PMID- 22143392
TI  - Are middle schools harmful? The role of transition timing, classroom quality and
      school characteristics.
AB  - Are middle schools ill-suited for early adolescents, or can school
      characteristics account for any differences in student functioning? Achievement,
      school engagement, and perceived competence of children starting middle schools
      in 5th and 6th grades were compared to those of their same-grade peers in
      elementary schools in a national, longitudinal sample (NICHD Study of Early Child
      Care and Youth Development, n = 855; 52% Female, 82% White). Classroom quality
      (observed and teacher-reported) and school characteristics (composition and size)
      were considered as explanations for any relationships between school-level and
      student functioning. Fifth grade middle school students did not differ from those
      in elementary school, but students entering middle school in 6th grade, compared
      to those in elementary school, experienced lower classroom quality, which in turn
      predicted slightly lower achievement. They also had lower school engagement,
      explained by larger school size. Classroom quality and school characteristics
      predicted youth functioning regardless of school type. We suggest reshaping the
      research and policy debate with renewed focus on classroom quality and school
      size instead of grade organization.

PMID- 22143395
TI  - Tregs:  application for solid-organ transplantation.
AB  - PURPOSE OF REVIEW: Transfer of human regulatory T cells (Tregs) has become an
      attractive therapeutic alternative to improve the long-term outcome in
      transplantation and thus reduce the side-effects of conventional
      immunosuppressive drugs. Here, we summarize the recent findings on human Treg
      subsets, their phenotype and in-vivo function. RECENT FINDINGS: In the last 2
      years, it has become apparent that several Treg subsets exist that specifically
      regulate Th1-driven, Th2-driven, or Th17-driven immune responses; these subsets
      are very unstable and rapidly change their phenotype, for example, there is loss
      of Foxp3 expression upon extensive ex-vivo expansion and only the administration
      of rapamycin has been shown to be able to interfere reproducibly. New humanized
      mouse models incorporating human solid-organ grafts have been developed, which
      have been used to test the human Treg in-vivo function, and the first human Treg
      cell products have been tested for safety and efficacy in stem cell
      transplantation. SUMMARY: With the recent findings, we have gained a better
      understanding of Treg heterogeneity, plasticity and function. Using the outcomes
      of clinical trials in stem cell transplantation, we have learned that adoptive
      therapy of Tregs is well tolerated and we are now awaiting the first result in
      solid-organ transplantation from the 'ONE Study'.

PMID- 22143394
TI  - Cyclosporine treatment improves mesenteric perfusion and attenuates necrotizing
      enterocolitis (NEC)-like intestinal injury in asphyxiated newborn piglets during
      reoxygenation.
AB  - PURPOSE: Asphyxia-related intestinal injury in neonates may present similar to
      necrotizing enterocolitis (NEC) and is partially associated with hypoxia
      reoxygenation injury. Cyclosporine has been shown to reduce myocardial cell death
      following ischemia-reperfusion. We hypothesize that cyclosporine treatment may
      attenuate NEC-like intestinal injury in asphyxiated newborn piglets during
      reoxygenation. METHODS: Twenty piglets (1-4 days old) were acutely anesthetized
      and instrumented for continuous monitoring of systemic hemodynamics and superior
      mesenteric arterial (SMA) flow. After stabilization, normocapnic alveolar hypoxia
      (10-15% oxygen) was instituted for 2 h followed by reoxygenation with 100% oxygen
      for 0.5 h, then 21% for 3.5 h. The piglets were blindly block-randomized to
      receive cyclosporine (10 mg/kg) or placebo (normal saline) boluses at 5 min of
      reoxygenation (n = 8/group). A sham-operated group was included (n = 4) and
      received no hypoxia-reoxygenation. Intestinal samples were collected for tissue
      lactate and histological assessment (Park's criteria). RESULTS: At 2 h of
      hypoxia, piglets had cardiogenic shock (cardiac output 45% of baseline),
      hypotension (mean arterial pressure 30 mmHg), acidosis (pH 7.04), and decreased
      superior mesenteric perfusion (all P < 0.05 vs. sham-operated group, ANOVA).
      Cyclosporine treatment increased SMA flow (114 +/- 6 vs. 78 +/- 19% of baseline
      of controls, respectively) with improved SMA oxygen delivery and intestinal
      tissue lactate (all P < 0.05). Some control piglets had NEC-like injuries
      including pneumatosis intestinalis, which were attenuated in cyclosporine-treated
      piglets (P < 0.05 vs. controls). CONCLUSIONS: This is the first study to
      demonstrate that post-resuscitation administration of cyclosporine improves
      mesenteric perfusion and attenuates NEC-like intestinal injury in newborn piglets
      following asphyxia-reoxygenation.

PMID- 22143396
TI  - Measuring fast calcium fluxes in cardiomyocytes.
AB  - Cardiomyocytes have multiple Ca(2+) fluxes of varying duration that work together
      to optimize function (1,2). Changes in Ca(2+) activity in response to
      extracellular agents is predominantly regulated by the phospholipase Cbeta-
      Galpha(q;) pathway localized on the plasma membrane which is stimulated by agents
      such as acetylcholine (3,4). We have recently found that plasma membrane protein
      domains called caveolae(5,6) can entrap activated Galpha(q;)(7). This entrapment
      has the effect of stabilizing the activated state of Galpha(q;) and resulting in
      prolonged Ca(2+) signals in cardiomyocytes and other cell types(8). We uncovered
      this surprising result by measuring dynamic calcium responses on a fast scale in
      living cardiomyocytes. Briefly, cells are loaded with a fluorescent Ca(2+)
      indicator. In our studies, we used Ca(2+) Green (Invitrogen, Inc.) which exhibits
      an increase in fluorescence emission intensity upon binding of calcium ions. The
      fluorescence intensity is then recorded for using a line-scan mode of a laser
      scanning confocal microscope. This method allows rapid acquisition of the time
      course of fluorescence intensity in pixels along a selected line, producing
      several hundreds of time traces on the microsecond time scale. These very fast
      traces are transferred into excel and then into Sigmaplot for analysis, and are
      compared to traces obtained for electronic noise, free dye, and other controls.
      To dissect Ca(2+) responses of different flux rates, we performed a histogram
      analysis that binned pixel intensities with time. Binning allows us to group over
      500 traces of scans and visualize the compiled results spatially and temporally
      on a single plot. Thus, the slow Ca(2+) waves that are difficult to discern when
      the scans are overlaid due to different peak placement and noise, can be readily
      seen in the binned histograms. Very fast fluxes in the time scale of the
      measurement show a narrow distribution of intensities in the very short time bins
      whereas longer Ca(2+) waves show binned data with a broad distribution over
      longer time bins. These different time distributions allow us to dissect the
      timing of Ca(2+)fluxes in the cells, and to determine their impact on various
      cellular events.

PMID- 22143397
TI  - Analysis of the site-specific integration system of the Streptomyces aureofaciens
      phage MU1/6.
AB  - The bacteriophage MU1/6 integrates its DNA into the chromosome of tetracycline
      producing strains of Streptomyces aureofaciens by a site-specific recombination
      process. A bioinformatic analysis of the MU1/6 genome revealed that orf5 encodes
      a putative integrase, a basic protein of 416 amino acids. The MU1/6 integrase was
      found to belong to the integrase family of site-specific tyrosine recombinases.
      The phage attachment site (attP) was localized downstream of the int gene. The
      attachment junctions (attL and attR) were determined, allowing identification of
      the bacterial attachment site (attB). All attachment sites shared a 46-bp common
      core sequence within which a site-specific recombination occurs. This core
      sequence comprises the 3' end of a putative tRNA(Thr) gene (anticodon TGT) which
      is completely restored in attL after integration of the phage into the host
      genome. An integration vector containing MU1/6 int-attP region was inserted
      stably into the S. aureofaciens B96, S. lividans TK24, and S. coelicolor A3. The
      MU1/6 integrase was shown to be functional in vivo in heterologous Escherichia
      coli without any other factors encoded by Streptomyces. In vitro recombination
      assay using purified MU1/6 integrase demonstrated its ability to catalyze
      integrative recombination in the presence of a crude extract of E. coli cells.

PMID- 22143399
TI  - Dynamic assessment of 'valvular reserve capacity' in patients with rheumatic
      mitral stenosis.
AB  - AIMS: Mitral stenosis (MS) may exhibit a dynamic valvular reserve. When resting
      gradients and systolic pulmonary pressure (sPAP) do not reflect the real severity
      of the disease, a dynamic evaluation becomes necessary. The aim of the study was
      to assess the clinical utility of exercise echocardiography in symptomatic
      patients with apparently subcritical MS. METHODS AND RESULTS: One hundred and
      thirty consecutive patients were referred for symptomatic MS. Patients with
      unimpressive resting MVA (>1-1.5 cm(2)) and mean PG (>=5-9 mmHg) underwent
      exercise echocardiography. Cardiac performance and mitral indices (MVA, peak/mean
      PG, sPAP) were measured. Exhaustion of valvular reserve capacity under exercise
      was defined as appearance of symptoms and sPAP > 60 mmHg. Forty-six patients
      (35%) (age: 53 +/- 10 years; 74%, female) with resting MVA (1.2 +/- 0.36 cm(2)),
      mean PG (6.8 +/- 2.7 mmHg), and sPAP (38 +/- 7 mmHg) inconsistent with symptoms
      underwent stress echocardiography. Exercise was stopped for dyspnoea (76%) or
      fatigue (24%). At peak workloads (57.2 +/- 21.8 Watts), increased mean PG (17.2
      +/- 4.8 mmHg, P< 0.001) and sPAP (67.4 +/- 11.4 mmHg; P< 0.0001) were observed,
      without change in MVA (1.25 +/- 0.4 cm(2); P= n.s.). At univariate analysis,
      predictors of adaptation to exercise were age (-0.345; P = 0.024), mean PG
      (0.339; P= 0.023), and sPAP (0.354; P= 0.024); at multivariate analysis, best
      predictor was resting mean PG, although correlation was poor (-0.339; P= 0.015).
      CONCLUSION: In MS with limiting symptoms despite unimpressive findings at rest,
      valvular capacity exhaustion should be tested on a dynamic background, as no
      single resting index can predict potential haemodynamic adaptation to exercise.
      In such context, the contribution of exercise echocardiography remains extremely
      valuable.

PMID- 22143400
TI  - Different impacts of acute myocardial infarction on left ventricular apical and
      basal rotation.
AB  - AIMS: The impacts of acute myocardial infarction (AMI) with different regional
      wall motion abnormalities on left ventricular (LV) rotation have not been well
      investigated. We assessed the impacts of AMI on LV rotational mechanics and to
      compare the alterations in basal and apical rotation between patients with
      anterior and inferior AMI. METHODS AND RESULTS: Thirty-five patients with
      anterior AMI and 31 patients with inferior AMI who had a single culprit lesion
      were analysed. Thirty age-matched subjects were included for controls. The apical
      and basal rotations were obtained and LV twist and torsion were measured by two
      dimensional speckle tracking imaging. Compared with normal, LV twist was reduced
      in all AMI patients. The basal rotation was larger in anterior AMI than in
      inferior AMI and normal (-9.0 +/- 2.6 vs. -3.4 +/- 2.1 degrees  and -6.0 +/- 1.9
      degrees , P < 0.001), although the apical rotation was lower in anterior AMI. As
      a result, LV twist and torsion were not different between anterior AMI and
      inferior AMI (17.0 +/- 4.6 vs. 16.7 +/- 3.3 degrees  and 2.08 +/- 0.59 vs. 2.07
      +/- 0.44 degrees /cm, P = NS, respectively), although LV ejection fraction was
      lower in anterior AMI. By multivariate analysis, LV torsion [odds ratio (OR)
      =0.13, 95% confidential interval (CI) = 0.02-0.75, P = 0.02] and basal rotation
      (OR = 0.67, 95% CI = 0.45-1.00, P = 0.05) were independently related to LV
      recovery in patients with anterior AMI and in patients with inferior AMI,
      respectively. CONCLUSION: Although LV twist and torsion were decreased either by
      reduced apical and basal rotation in AMI patients; the basal rotation was rather
      increased in anterior AMI. LV functional recovery can be predicted by LV torsion
      in anterior AMI and by basal rotation in inferior AMI. The basal rotation has
      often been ignored; however, our findings suggest that the basal rotation has an
      important role in LV function.

PMID- 22143401
TI  - Single photon emission computed tomography myocardial perfusion imaging to detect
      cardiac allograft vasculopathy.
AB  - AIMS: Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and
      mortality in cardiac transplant recipients. This study evaluates the usefulness
      of single photon emission computed tomography (SPECT) and various SPECT-derived
      diastolic variables to detect CAV in heart transplant patients. METHODS AND
      RESULTS: A retrospective review of 141 SPECT studies with corresponding coronary
      angiograms within 12 months was performed on 99 transplant recipients. Diastolic
      function was assessed using computer-derived measures of peak filling rate (PFR),
      time to peak filling rate (TPFR), and mean first one-third filling rate (MFR/3).
      Angiography identified CAV in 53 of the 141 studies (38%). Of the 53, SPECT
      identified 7 with reversible myocardial defects (sensitivity 13%) and stress
      induced electrocardiographic evidence of ischaemia was seen in one patient
      (sensitivity 2%). SPECT imaging was negative in 86 of the 88 negative coronary
      angiograms (specificity 98%). The positive predictive value and negative
      predictive value were 78 and 65%, respectively. If a more stringent definition of
      CAV was used (>=70% stenosis), the sensitivity and specificity were unchanged (14
      and 98%, respectively). There was no statistical difference in diastolic
      variables between patients with or without angiographic evidence of CAV in regard
      to PFR (3.57 +/- 1.14 vs. 3.18 +/- 1.21 EDV/s, P = 0.90), TPFR (149 +/- 32 vs.
      153 +/- 43 ms, P = 0.33), or MFR/3 (1.37 +/- 0.43 vs. 1.27 +/- 0.42 EDV/s, P =
      0.94). CONCLUSION: Adenosine stress/rest technetium-99m tetrofosmin-gated SPECT
      is not a sensitive test for detection of CAV in heart transplant recipients.
      Diastolic dysfunction, as assessed by SPECT, was not shown to be associated with
      development of CAV.

PMID- 22143402
TI  - Catalytic asymmetric cleavage of sp3 C-N bonds for access to highly
      enantioenriched N-benzylic sulfonamides.
AB  - In the presence of 10 mol% of a chiral phosphoric acid, a variety of racemic N
      benzylic sulfonamides having N-(3-indolyl)methyl groups smoothly undergo kinetic
      resolution with benzyl thiol at 0  degrees C or at room temperature and the
      remaining sulfonamides are recovered in moderate to excellent yields and with
      excellent ee.

PMID- 22143398
TI  - SigB-dependent tolerance to protein synthesis-inhibiting antibiotics in Listeria
      monocytogenes EGDe.
AB  - The alternative sigma factor SigB in food-borne pathogen Listeria monocytogenes
      was determined in this study to be required for tolerance to protein synthesis
      inhibiting antibiotics. The minimum inhibitory concentrations of tetracycline HCl
      and gentamicin sulphate against EGDeDeltasigB were two- and fourfold less than
      those for EGDe, respectively. The ability of EGDeDeltasigB to overcome the growth
      arrest caused by erythromycin and rifampin was also weaker than that of EGDe. The
      transcription analysis of four genetic loci (known to be induced by rifampin in
      Bacillus subtili) kat, fri, ropB and rsbU in EGDe and EGDeDeltasigB in the
      absence or presence of rifampin revealed that: (1) expression of kat and fri
      genes is sigma (B) dependent, but only the former is inducible by rifampin
      stress; (2) the transcriptional level of rpoB gene was stable under all the
      experimental conditions, while that of rsbU in EGDeDeltasigB was remarkably
      higher in the absence of rifampin and significantly increased in EGDe but reduced
      in EGDeDeltasigB after rifampin application, when compared to those in EGDe and
      EGDeDeltasigB control without antibiotic, respectively. These results suggest
      that complex physiological reactions to tolerance of the antibiotic stress are
      variably regulated in bacteria, and in contrast to B. subtilis, rsbU in
      EGDeDeltasigB may compensate for the sigma (B)-dependent genes that are necessary
      for tolerance to rifampin stress and therefore plays a role in overcoming the
      antibiotic-triggered growth arrest.

PMID- 22143403
TI  - Bayesian analysis on meta-analysis of case-control studies accounting for within
      study correlation.
AB  - In retrospective studies, odds ratio is often used as the measure of association.
      Under independent beta prior assumption, the exact posterior distribution of odds
      ratio given a single 2 * 2 table has been derived in the literature. However,
      independence between risks within the same study may be an oversimplified
      assumption because cases and controls in the same study are likely to share some
      common factors and thus to be correlated. Furthermore, in a meta-analysis of case
      control studies, investigators usually have multiple 2 * 2 tables. In this
      article, we first extend the published results on a single 2 * 2 table to allow
      within study prior correlation while retaining the advantage of closed-form
      posterior formula, and then extend the results to multiple 2 * 2 tables and
      regression setting. The hyperparameters, including within study correlation, are
      estimated via an empirical Bayes approach. The overall odds ratio and the exact
      posterior distribution of the study-specific odds ratio are inferred based on the
      estimated hyperparameters. We conduct simulation studies to verify our exact
      posterior distribution formulas and investigate the finite sample properties of
      the inference for the overall odds ratio. The results are illustrated through a
      twin study for genetic heritability and a meta-analysis for the association
      between the N-acetyltransferase 2 (NAT2) acetylation status and colorectal
      cancer.

PMID- 22143404
TI  - Slope estimation for informatively right censored longitudinal data modelling the
      number of observations using geometric and Poisson distributions: application to
      renal transplant cohort.
AB  - Analysis of longitudinal data is often complicated by the presence of informative
      right censoring. This type of censoring should be accounted for in the analysis
      so that valid slope estimates are attained. In this study, we developed a new
      likelihood-based approach wherein the likelihood function is integrated over
      random effects to obtain a marginal likelihood function. Maximum likelihood
      estimates for the population slope were acquired by direct maximisation of the
      marginal likelihood function and empirical Bayes estimates for the individual
      slopes were generated using Gaussian quadrature. The performance of the model was
      assessed using the geometric and Poisson distributions to model the number of
      observations for every individual subject. Our model generated valid estimates
      for the slopes under both distributions with minimal bias and mean squared
      errors. Our sensitivity analysis confirmed the robustness of the model to
      assumptions pertaining to the underlying distribution and demonstrated its
      insensitivity to normality assumptions. Moreover, superiority of the model in
      terms of accuracy of slope estimates was consistently shown across the different
      levels of censoring in comparison to the naive and bootstrap approaches. This
      model was illustrated using the cohort of renal transplant patients and estimates
      of the slopes that are adjusted for informative right censoring were acquired. 

PMID- 22143405
TI  - A two-way enriched clinical trial design: combining advantages of placebo lead-in
      and randomized withdrawal.
AB  - A new clinical trial design, designated the two-way enriched design (TED), is
      introduced, which augments the standard randomized placebo-controlled trial with
      second-stage enrichment designs in placebo non-responders and drug responders.
      The trial is run in two stages. In the first stage, patients are randomized
      between drug and placebo. In the second stage, placebo non-responders are re
      randomized between drug and placebo and drug responders are re-randomized between
      drug and placebo. All first-stage data, and second-stage data from first-stage
      placebo non-responders and first-stage drug responders, are utilized in the
      efficacy analysis. The authors developed one, two and three degrees of freedom
      score tests for treatment effect in the TED and give formulae for asymptotic
      power and for sample size computations. The authors compute the optimal
      allocation ratio between drug and placebo in the first stage for the TED and
      compare the operating characteristics of the design to the standard parallel
      clinical trial, placebo lead-in and randomized withdrawal designs. Two motivating
      examples from different disease areas are presented to illustrate the possible
      design considerations. 

PMID- 22143407
TI  - Asymmetric [3+2] annulation of allenes with maleimides catalyzed by dipeptide
      derived phosphines: facile creation of functionalized bicyclic cyclopentenes
      containing two tertiary stereogenic centers.
AB  - D-Threonine-L-tert-leucine-derived bifunctional phosphine, Cat. 11, catalyzed
      highly enantioselective [3+2] annulation of maleimides with allenes has been
      disclosed, allowing the synthesis of optically active functionalized bicyclic
      cyclopentenes containing two tertiary stereogenic centers in good to high yields
      along with good to high enantioselectivities.

PMID- 22143406
TI  - MK-801 alters Na+, K+-ATPase activity and oxidative status in zebrafish brain:
      reversal by antipsychotic drugs.
AB  - Schizophrenia is a debilitating mental disorder with a global prevalence of 1%
      and its etiology remains poorly understood. In the current study we investigated
      the influence of antipsychotic drugs on the effects of MK-801 administration,
      which is a drug that mimics biochemical changes observed in schizophrenia, on
      Na(+), K(+)-ATPase activity and some parameters of oxidative stress in zebrafish
      brain. Our results showed that MK-801 treatment significantly decreased Na(+),
      K(+)-ATPase activity, and all antipsychotics tested prevented such effects. Acute
      MK-801 treatment did not alter reactive oxygen/nitrogen species by 2'7'
      dichlorofluorscein (H2DCF) oxidation assay, but increased the levels of
      thiobarbituric acid reactive substances (TBARS), when compared with controls.
      Some antipsychotics such as sulpiride, olanzapine, and haloperidol prevented the
      increase of TBARS caused by MK-801. These findings indicate oxidative damage
      might be a mechanism involved in the decrease of Na(+), K(+)-ATPase activity
      induced by MK-801. The parameters evaluated in this study had not yet been tested
      in this animal model using the MK-801, suggesting that zebrafish is an animal
      model that can contribute for providing information on potential treatments and
      disease characteristics.

PMID- 22143408
TI  - Prevalence and correlates of HCV, HVB, and HIV infection among prison inmates and
      staff, Hungary.
AB  - The aim of this national, multicenter, cross-sectional study was to assess the
      prevalence of hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency
      viruses (HIV) among prisoners, and to identify related risk behaviors including
      injection drug use. Overall, 4,894 inmates from 20 prisons were enrolled. To have
      a comparison group, prison staff were also asked to take part. Altogether, 1,553
      of the 4,894 inmates from seven prisons completed a questionnaire on risk
      behaviors. According to the survey, 1.5%, 4.9%, and 0.04% of the prisoners were
      tested positive for HBsAg, anti-HCV and anti-HIV, respectively. These prevalence
      data are among the lowest reported from prisons worldwide, although comparable to
      the Central European data. The prevalence of HBV, HCV, and HIV in the Hungarian
      prison staff was low (0.38%, 0.47%, and 0%, respectively). The rate of HCV
      infection was significantly higher among inmates who have ever injected drugs
      (22.5%) than among inmates who reported they had never injected drugs (1.1%).
      This first prevalence study of illegal drug injection-related viral infections
      among Hungarian prisoners points out that ever injecting drugs is the main reason
      for HCV infection among inmates. The opportunity to reach drug users infected
      with HCV for treatment underlines the importance of screening programs for blood
      borne viruses in prisons.

PMID- 22143409
TI  - Neighborhood contexts experienced by young Mexican-American women: enhancing our
      understanding of risk for early childbearing.
AB  - Young Mexican-American women are disproportionately affected by teen pregnancy
      and early childbearing. While many of the studies that have investigated this
      population's high risk for early childbearing have focused predominantly on micro
      level factors, a growing body of research has demonstrated the importance of
      neighborhood-level factors in shaping risk for this outcome. In order to
      elucidate the role of neighborhood context with regards to early childbearing
      among adolescent Mexican-American women, it is important to understand what these
      young women consider to be their neighborhood context and how they experience
      these contexts. This study utilized a mixed-methods design incorporating
      participatory photography, photo-elicitation, and focus groups in order to gain a
      more nuanced understanding of how neighborhood context is conceptualized and
      experienced by Mexican-American young women, and how these experiences may
      influence risk for early childbearing. Major findings include: (1) participants
      view the blocks on which they live as their neighborhood, but their exposure to
      neighborhood context extends beyond these blocks and includes the transient
      spaces they move through daily; and (2) within their neighborhood contexts,
      participants are influenced by experiences of discrimination and the presence of
      gangs and violence. These findings point to the importance of neighborhood-level
      factors in the lives of adolescent Mexican-American women, and may be used to
      inform future studies looking at the role of neighborhood context in shaping risk
      for early childbearing among this population.

PMID- 22143412
TI  - Histomorphometry of the ligaments using a generic-purpose image processing
      software, a new strategy for semi-automatized measurements.
AB  - Gold chloride technique can be combined with Adobe Photoshop(r) software to yield
      a quantitative assessment of the different areas in heterogeneous structures as
      are ligament. A semi-automatized method based on the sum of two- and three
      dimensional morphological criteria upon colorimetric criteria allows the
      identification and measurement of the area occupied by a structure of interest.
      It also allows the quantification of color intensity to differentiate structures
      with similar staining avidity, like vessels and nerves. This computer-assisted,
      semiquantitative procedure for computerized morphometry is relatively simple to
      perform. The accuracy, efficiency, and reproducibility of this method based on a
      commercially available imaging program were considered adequate when tested on
      the anterior cruciate ligament of the cat. Image normalization by trained
      observers using a commercially available software package designed for
      photography, applied to a sample randomly chosen, has provided the means of
      making reproducible measurements of heterogeneous structures.

PMID- 22143413
TI  - Demystifying occupational stress and fatigue through the creation of an adaptive
      end-user profiling system.

PMID- 22143410
TI  - The insidious problem of fatigue in medical imaging practice.

PMID- 22143411
TI  - Innovation strategies for combating occupational stress and fatigue in medical
      imaging.

PMID- 22143415
TI  - Methylene tetrahydrofolate reductase gene polymorphisms and their association
      with methotrexate toxicity:  a meta-analysis.
AB  - OBJECTIVE: A systematic review and a meta-analysis were conducted, to investigate
      the possible association of methylene tetrahydrofolate reductase (MTHFR) gene
      polymorphisms with adverse effects related to methotrexate (MTX). METHODS: A
      systematic literature search in PubMed retrieved a total of 44 studies (42 unique
      articles). Two polymorphisms were included in the meta-analysis: C677T and
      A1298C. Random effect models were used in the analysis. Odds ratios along with
      their 95% confidence intervals were computed to compare the distribution of
      alleles and genotypes between cases and controls. RESULTS: The analysis
      highlighted a significant association of C677T polymorphism with overall MTX
      toxicity, hepatotoxicity, hematological toxicity, and neurotoxicity. It also
      revealed an association with MTX toxicity in patients with rheumatoid arthritis.
      In contrast, a protective effect of C677T MTHFR polymorphism on acute graft
      versus-host disease and on patients treated with hematopoietic cell
      transplantation was found. As for the A1298C polymorphism, a statistically
      significant association with overall MTX toxicity and a protective role of the
      polymorphism in rheumatoid arthritis patients was detected. CONCLUSION: These
      results indicate the association of MTHFR polymorphisms with MTX toxicity.
      However, further studies are needed to reveal the underlying biological mechanism
      of the association.

PMID- 22143414
TI  - Genetic variation in cholesterol ester transfer protein, serum CETP activity, and
      coronary artery disease risk in Asian Indian diabetic cohort.
AB  - BACKGROUND: The role of cholesteryl ester transfer protein (CETP) in the
      metabolism of high-density lipoprotein cholesterol (HDL-C) is well studied but
      still controversial. More recently, genome-wide association studies and meta
      analyses reported the association of a promoter variant (rs3764261) with HDL-C in
      Caucasians and other ethnic groups. In this study, we have examined the role of
      genetic variation in the promoter region of CETP with HDL-C, CETP activity,
      coronary artery disease (CAD), CAD risk factors, and the interaction of genetic
      factors with environment in a unique diabetic cohort of Asian Indian Sikhs.
      METHODS AND RESULTS: We genotyped four variants; three tagging single nucleotide
      polymorphisms from promoter (rs3764261, rs12447924, rs4783961) and one intronic
      variant (rs708272 Taq1B) on 2431 individuals from the Sikh Diabetes study. Two
      variants (rs3764261 and rs708272) exhibited a strong association with HDL-C in
      both normoglycemic controls (beta=0.12; P=9.35*10 for rs3764261; beta=0.10,
      P=0.002 for rs708272) and diabetic cases (beta=0.07, P=0.016 for rs3764261;
      beta=0.08, P=0.005 for rs708272) with increased levels among minor homozygous
      'AA' carriers. In addition, the same 'A' allele carriers in rs3764261 showed a
      significant decrease in systolic blood pressure (beta=-0.08, P=0.002) in
      normoglycemic controls. Haplotype analysis of rs3764261, rs12447924, rs4783961,
      and rs708272 further revealed a significant association of 'ATAA' haplotype with
      an increased HDL-C (beta=2.71, P=6.38*10) and 'CTAG' haplotype with decreased HDL
      C levels (beta=-1.78, P=2.5*10). Although there was no direct association of CETP
      activity and CETP polymorphisms, low CETP activity was associated with an
      increased risk to CAD (age, BMI, and sex-adjusted odds ratio=2.2; 95% confidence
      interval: 1.4-3.4; P=0.001) in this study. Our data revealed a strong interaction
      of rs3764261 and rs708272 for affecting the association between CETP activity and
      HDL-C levels (P=2.2*10 and P=4.4*10, respectively). CONCLUSION: Our results, in
      conjunction with earlier reports confirm low CETP activity to be associated with
      higher CAD risk. Although there was no direct association of CETP activity with
      CETP polymorphisms, our findings revealed a significant interaction between CETP
      variants and CETP activity for affecting HDL-C levels. These results urge a
      deeper evaluation of the individual genetic variation in the CETP before
      implementing pharmaceutical intervention of blocking CETP for preventing CAD
      events.

PMID- 22143418
TI  - Heavy metal characteristics in Kocani Field plant system (Republic of Macedonia).
AB  - Heavy metal contamination of soils is widespread and induces a long-term risk to
      ecosystem health. This research focuses on the heavy metal contamination,
      transfer values and risk assessment in the Kocani Field plant system (Republic of
      Macedonia). To identify the heavy metal concentrations in Kocani crops (rice and
      maize), the geochemical analysis was performed by inductive coupled plasma mass
      spectrometer and thereupon the transfer factor (TF) and estimated daily intake
      amount values were calculated. The highest As, Cd, Mo, Pb and Zn values were
      determined in the rice samples grown in the paddy fields near the Zletovska
      River. The highest Pb and Mo concentrations measured in the maize samples were
      from the maize fields near the Zletovska River and Ciflik city. High TF values
      for Mo, Zn, Cd and Cu revealed a strong accumulation of Mo, Zn and Cd by rice and
      Mo and Zn by maize crops. The results of the estimated daily intake showed that
      the regular consumption of rice and maize crops containing the highest Cd, Mo, Pb
      and Zn concentrations could pose a serious threat to human health, because the
      daily intake of Cd, Mo, Pb and Zn for crops grown in the fields around the
      Zletovska River exceeded the recommended provisional tolerable daily intake
      values. Taking into account the results, the area around Zletovska River is
      considered as the most anthropogenically impacted part of Kocani Field.

PMID- 22143416
TI  - Asymptomatic bacteriuria: when the treatment is worse than the disease.
AB  - Asymptomatic bacteriuria (ABU) is a condition in which bacteria are present in a
      noncontaminated urine sample collected from a patient without signs or symptoms
      related to the urinary tract. ABU must be distinguished from symptomatic UTI by
      the absence of signs and symptoms compatible with UTI or by clinical
      determination that a nonurinary etiology accounts for the patient's symptoms.
      Interactions between the organism, the host, and the bladder environment
      determine whether bacteriuria leads to ABU or to UTI. ABU is a very common
      condition that is often treated unnecessarily with antibiotics-it should be
      detected and treated in pregnant women and patients undergoing urologic surgery,
      but in most other patient groups, treatment does not confer benefit and can be
      harmful. A change in prescribing behavior for ABU has been achieved through
      several fairly high-intensity interventions, such as interactive educational
      sessions for physicians, but whether these improvements persist beyond the study
      period is not known. Further research is needed to determine whether screening
      for and treatment of ABU is beneficial in patients with renal transplants,
      patients with orthotopic neobladders, patients undergoing prosthetic joint
      implantation, and patients with neutropenia.

PMID- 22143419
TI  - Cholecystectomy in the very elderly--is 90 the new 70?
AB  - BACKGROUND: Nonagenarians are the fastest growing sector of population across
      Western Europe. Although prevalence of gallstone disease is high, elective
      cholecystectomy is still controversial in this age group. METHODS: A
      retrospective chart review was conducted of cholecystectomies done in patients
      over 90 years of age at our institution between 2004 and December 2009. During
      this period, a total of 3,009 cholecystectomies were performed on patients of all
      ages. Data collected included demographics, patient comorbidities, indications
      for surgery, type of surgery performed, intraoperative findings, histology,
      perioperative morbidity and mortality. RESULTS: Twenty-two nonagenarians (18
      females) underwent cholecystectomy during the study period. Of these patients, 19
      patients (86%) had diabetes, 16 (73%) had hypertension, and 10 (45%) had coronary
      artery disease. Twenty patients (91%) underwent an emergency procedure. In two
      patients, cholecystectomy was indicated for non-resolving pain after attempted
      conservative therapy, only two patients were operated electively. Laparoscopic
      cholecystectomy was attempted in 13 patients (59%), 3 patients needed a
      conversion, and 9 patients (41%) considered unfit to undergo a laparoscopic
      approach had an open procedure. Mean operation time was 83 min. Histology showed
      gangrenous cholecystitis in six (27%) patients. The mean length of stay was 10
      days (4-23 days). Two patients (8.3%) required intensive care following surgery.
      There were no common bile duct injuries, one patient had a cystic stump leak. One
      patient died in the postoperative period (4.6%). All patients with an emergency
      operation were classified as at least ASA III. Conversion rate, percentage of
      open procedures, percentage of advanced histology, ASA score, and hospital stay
      were significantly higher when compared to all patients. CONCLUSION: Our study
      demonstrates that in unselected nonagenarians,cholecystectomy is safe with
      acceptable perioperative morbidity and mortality even as an emergency procedure.
      However, our data also suggests that cholecystitis appears to be a neglected
      condition in this age group.

PMID- 22143420
TI  - Tumor size and depth predict rate of lymph node metastasis in colon carcinoids
      and can be used to select patients for endoscopic resection.
AB  - BACKGROUND: Regional lymphadenectomy is recommended for all colon carcinoids,
      whereas resection without lymphadenectomy is accepted for selected appendiceal
      and rectal carcinoids. We examined the relation of tumor size and depth to lymph
      node metastasis in order to determine whether colon carcinoids could be selected
      for endoscopic resection. METHODS: Patients were identified from the Surveillance
      Epidemiology and End Results Registry. The Pearson chi-square and the log rank
      tests were used. P < 0.05 was considered significant. RESULTS: We identified 929
      patients who underwent resection of localized colon carcinoids without distant
      metastasis diagnosed from 1973 to 2006. The diagnosis of small and superficial
      tumors increased over time (p < 0.001). The presence of lymph node metastasis was
      adversely associated with survival (p < 0.001); however, there was only a trend
      toward independence on multivariate analysis (p = 0.054). Tumor size and depth
      were associated with lymph node metastasis (p < 0.001, p < 0.001). Tumors were
      subgrouped by size and depth to find cases with a low risk of lymph node
      metastasis. Intramucosal tumors < 1 cm had a 4% rate of lymph node metastasis,
      while all other subgroups had rates >= 14%. CONCLUSION: Tumor size and depth
      predict lymph node metastasis for colon carcinoids. Endoscopic resection may be
      appropriate for intramucosal tumors <1 cm.

PMID- 22143421
TI  - Detection and isolation of circulating melanoma cells using photoacoustic
      flowmetry.
AB  - Circulating tumor cells (CTCs) are those cells that have separated from a
      macroscopic tumor and spread through the blood and lymph systems to seed
      secondary tumors(1,2,3).  CTCs are indicators of metastatic disease and their
      detection in blood samples may be used to diagnose cancer and monitor a patient's
      response to therapy.  Since CTCs are rare, comprising about one tumor cell among
      billions of normal blood cells in advanced cancer patients, their detection and
      enumeration is a difficult task.  We exploit the presence of pigment in most
      melanoma cells to generate photoacoustic, or laser induced ultrasonic waves in a
      custom flow cytometer for detection of circulating melanoma cells (CMCs)(4,5). 
      This process entails separating a whole blood sample using centrifugation and
      obtaining the white blood cell layer.  If present in whole blood, CMCs will
      separate with the white blood cells due to similar density.  These cells are
      resuspended in phosphate buffered saline (PBS) and introduced into the flowmeter.
      Rather than a continuous flow of the blood cell suspension, we induced two phase
      flow in order to capture these cells for further study.  In two phase flow, two
      immiscible liquids in a microfluidic system meet at a junction and form
      alternating slugs of liquid(6,7). PBS suspended white blood cells and air form
      microliter slugs that are sequentially irradiated with laser light.  The addition
      of a surfactant to the liquid phase allows uniform slug formation and the user
      can create different sized slugs by altering the flow rates of the two phases. 
      Slugs of air and slugs of PBS with white blood cells contain no light absorbers
      and hence, do not produce photoacoustic waves.  However, slugs of white blood
      cells that contain even single CMCs absorb laser light and produce high frequency
      acoustic waves.  These slugs that generate photoacoustic waves are sequestered
      and collected for cytochemical staining for verification of CMCs.

PMID- 22143422
TI  - Exonuclease-assisted cascaded recycling amplification for label-free detection of
      DNA.
AB  - The network consisting of three kinds of unlabeled stem-loop DNA molecular
      beacons (MBs) is activated by target DNA in the presence of exonuclease-III (Exo
      III), achieving the concept of exonuclease-assisted cascaded recycling
      amplification (Exo-CRA) for DNA detection with a wide dynamic range of 8 orders
      of magnitude.

PMID- 22143423
TI  - Cardiovascular magnetic resonance imaging (CMR) reveals characteristic pattern of
      myocardial damage in patients with mitochondrial myopathy.
AB  - BACKGROUND: Mitochondrial myopathy comprises various clinical subforms of
      neuromuscular disorders that are characterised by impaired mitochondrial energy
      metabolism due to dysfunction of the mitochondrial respiratory chain. No
      comprehensive and targeted cardiovascular magnetic resonance (CMR) studies have
      been performed so far in patients with mitochondrial disorders. The present study
      aimed at characterising cardiac disease manifestations in patients with
      mitochondrial myopathy and elucidating the in vivo cardiac damage pattern of
      patients with different subforms of mitochondrial disease by CMR studies. METHODS
      AND RESULTS: In a prospective study, 37 patients with mitochondrial myopathy
      underwent comprehensive neurological and cardiac evaluations including physical
      examination, resting ECG and CMR. The CMR studies comprised cine-CMR, T2-weighted
      "edema" imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging.
      Various patterns and degrees of skeletal myopathy were present in the
      participants of this study, whereas clinical symptoms such as chest pain symptoms
      (in eight (22%) patients) and various degrees of dyspnea (in 16 (43%) patients)
      were less frequent. Pathological ECG findings were documented in eight (22%)
      patients. T2-weighted "edema" imaging was positive in one (3%) patient with MELAS
      (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes)
      only. LGE imaging demonstrated the presence of non-ischemic LGE in 12 (32%)
      patients: 10 out of 24 (42%) patients with CPEO (chronic progressive external
      ophthalmoplegia) or KSS (Kearns-Sayre syndrome) and 2 of 3 (67%) patients with
      MELAS were LGE positive. All 10 LGE-positive patients with CPEO or KSS
      demonstrated a potentially typical pattern of diffuse intramural LGE in the left
      ventricular (LV) inferolateral segments. CONCLUSIONS: Cardiac involvement is a
      frequent finding in patients with mitochondrial myopathy. A potentially
      characteristic pattern of diffuse intramural LGE in the LV inferolateral segments
      was identified in patients suffering from the subforms CPEO or KSS.

PMID- 22143424
TI  - Effects of radiofrequency energy on porcine articular cartilage: higher-power
      settings in ablation mode show lower thermal radiation injury.
AB  - PURPOSE: The purpose of this study was to compare the radiofrequency (RF) injury
      effect on cartilage in the different settings that are mostly used in clinical
      work under rigidly controlled laboratory conditions. METHODS: Twelve fresh
      porcine knees were used in our study. Five treatment areas were created on the
      femoral condyles of each knee: the control group, coagulation (setting 2) group,
      coagulation (setting 7) group, ablation (setting 2) group, and ablation (setting
      7) group. Hematoxylin/eosin staining, dual fluorescence staining, and the GAG
      content were observed to evaluate the histological cartilage changes, vacuolar
      cell rate of chondrocytes, depth of chondrocyte death, and detection of GAG
      content. RESULTS: Vacuolar cell rates of chondrocytes in each experimental group
      were higher than that in the control group (P < 0.05); there was no significant
      difference in vacuolar cell rate among experimental groups. Dual fluorescent
      staining showed that the ablation (setting 7) group had a smaller depth of cell
      death than did the coagulation (setting 2) group (P < 0.05); the other
      experimental groups showed no statistically significant difference (n.s.). In
      addition, there was no significant difference in GAG content between the
      experimental groups and control group (n.s.). CONCLUSIONS: The coagulation mode
      results in heavier thermal radiation injury to chondrocytes than does the
      ablation mode. Higher-power settings in the ablation mode result in lower thermal
      radiation injury and may be most suitable for cartilage debridement.

PMID- 22143426
TI  - Early functional outcome after subvastus or parapatellar approach in knee
      arthroplasty is comparable.

PMID- 22143425
TI  - Potential of healing a transected anterior cruciate ligament with genetically
      modified extracellular matrix bioscaffolds in a goat model.
AB  - PURPOSE: Biological augmentation to heal a torn anterior cruciate ligament (ACL)
      has gained significant interest. This study examined the potential advantages of
      using extracellular matrix (ECM) bioscaffolds from galactosyl-alpha(1,3)galactose
      deficient pigs to heal the transected ACL. METHODS: In 16 skeletally mature
      goats, the ACL in the right hindlimb was transected and repaired. In 9 of these
      animals, an ECM sheet was wrapped around the injury site and with an ECM hydrogel
      injected into the transected site. The remaining 7 animals were treated with
      suture repair only. The left hindlimb served as a sham-operated control. RESULTS:
      After 12 weeks, the healing ACL in the ECM-treated group showed an abundance of
      continuous neo-tissue formation, while only limited tissue growth was found after
      suture repair only. The cross-sectional area of the ACL from the ECM-treated
      group was similar to sham-operated controls (n.s.) and was 4.5 times those of the
      suture repair group (P < 0.05). The stiffness of the femur-ACL-tibia complexes
      from the ECM-treated group was 2.4 times those of the suture repair group (P <
      0.05). Furthermore, these values reached 48% of the sham-operated controls (53 +/
      19 N/mm and 112 +/- 21 N/mm, respectively, P < 0.05). CONCLUSIONS: The
      application of an ECM bioscaffold and hydrogel was found to accelerate the
      healing of a transected ACL following suture repair in the goat model with
      limited tissue hypertrophy and improvement in some of its biomechanical
      properties. Although more work is necessary to fully restore the function of the
      normal ACL, these early results offer a potential new approach to aid ACL
      healing.

PMID- 22143427
TI  - The steroid hormone 20-hydroxyecdysone upregulated the protein phosphatase 6 for
      the programmed cell death in the insect midgut.
AB  - Programmed cell death (PCD) plays an important role in insect midgut remodeling
      during metamorphosis. Insect midgut PCD is triggered by the steroid hormone 20
      hydroxyecdysone (20E) and it is mediated by a series of genes. However, the
      mechanism by which 20E triggers midgut PCD is still unclear. Here, we report a
      protein phosphatase 6 (PP6) from Helicoverpa armigera playing roles in midgut
      PCD. PP6 was expressed in the midgut during larval growth and it is significantly
      increased during metamorphosis. The increase was proven to be regulated by 20E.
      The juvenile hormone analog methoprene has no effect on PP6 expression. RNA
      interference analysis suggests that 20E upregulated the PP6 transcript levels
      through the ecdysone receptor EcRB1. PP6 knockdown by larval feeding or PP6 dsRNA
      injection resulted in the repression of the midgut PCD during the metamorphic
      stage. The mechanism was demonstrated to be through the suppression of genes such
      as Broad (Br), E74a, E75b, HR3, E93, rpr, and caspase, which are involved in 20E
      signaling pathway or midgut PCD. These findings suggest that PP6 is involved in
      the 20E signal transduction pathway and participates in the PCD in midgut.

PMID- 22143428
TI  - Synthesis and biological activity of new series of N-modified analogues of the
      N/OFQ(1-13)NH2 with aminophosphonate moiety.
AB  - New series of N-modified analogues of the N/OFQ(1-13)NH(2) with aminophosphonate
      moiety have been synthesized and investigated for biological activity. These
      peptides were prepared by solid-phase peptide synthesis-Fmoc-strategy. The
      N/OFQ(1-13)NH(2) analogues were tested for agonistic activity in vitro on
      electrically stimulated rat vas deferens smooth-muscle preparations isolated from
      Wistar albino rats. Our study has shown that the selectivity of the peptides
      containing 1-[(methoxyphosphono)methylamino]cycloalkanecarboxylic acids to the N
      side of Phe is not changed-they remain selective agonists of NOP receptors. The
      derivative with the largest ring (NOC-6) demonstrated efficacy similar to that of
      N/OFQ(1-13)NH(2), but in a 10-fold higher concentration. The agonistic activity
      of newly synthesized N-modified analogues of N/OFQ(1-13)NH(2) with
      aminophosphonate moiety was investigated for the first time.

PMID- 22143429
TI  - Carnosine derivatives: new multifunctional drug-like molecules.
AB  - Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide widely and
      abundantly distributed in the muscle and nervous tissues of several animal
      species. Many functions have been proposed for this compound because of its
      antioxidant and metal ion-chelator properties. Many potential therapeutic
      properties have been recognized especially related to the antioxidant activity,
      but the therapeutic uses are strongly limited by the mechanism governing its
      homeostasis. This fact has been the main reason for developing the synthesis of
      carnosine derivatives with interesting potentiality, but until now there have
      been very few applications. These derivatives could represent the future drugs
      for many pathologies related to oxidative stress and metal ion dyshomeostasis.

PMID- 22143430
TI  - Role of curcumin in the conversion of asparagine into acrylamide during heating.
AB  - This study aimed to investigate the ability of curcumin to convert asparagine
      into acrylamide during heating at different temperatures. Binary and ternary
      model systems of asparagine-curcumin and asparagine-curcumin-fructose were used
      to determine the role of curcumin on acrylamide formation in competitive and
      uncompetitive reaction conditions. The results indicated that curcumin could
      potentially contribute to acrylamide formation under long-term heating conditions
      as long as asparagine was present in the medium. The amount of acrylamide formed
      in the ternary system was slightly higher than in the binary system during
      heating (p < 0.05), because of the higher concentrations of carbonyl compounds
      initially available. The kinetic trends were similar in both model systems
      evidencing that fructose reacted with asparagine more rapidly than curcumin. The
      data reveal that acrylamide formation in the temperature range of 150-200 degrees
      C obeys Arrhenius law with activation energy of 79.1 kJ/mole. Data of this work
      showed the possibility that antioxidants having a carbonyl compound can react
      directly with ASN leading to acrylamide. The addition of antioxidants to foods
      may increase the formation of acrylamide upon long-term heating if free sugar
      concentration is low and ASN concentration is relatively high.

PMID- 22143431
TI  - The intriguing mission of neuropeptide Y in the immune system.
AB  - For many years, the central nervous system and the immune system were considered
      two autonomous entities. However, extensive research in the field of
      neuroimmunomodulation during the past decades has demonstrated the presence of
      different neuropeptides and their respective receptors in the immune cells. More
      importantly, it has provided evidence for the direct effects of neuropeptides on
      the immune cell functions. Neuropeptide Y (NPY) is generally considered the most
      abundant peptide in the central and peripheral nervous system. However, it is
      also distinguished by exhibiting pleiotropic functions in many other
      physiological systems, including the immune system. NPY affects the functions of
      the cells of the adaptive and innate immunity. In this respect, NPY is known to
      modulate immune cell trafficking, T helper cell differentiation, cytokine
      secretion, natural killer cell activity, phagocytosis and the production of
      reactive oxygen species. The specific Y receptors have been found in immune
      cells, and their expression is amplified upon immune stimulation. Different Y
      receptor subtypes may mediate an opposite effect of NPY on the particular
      function, thus underlining its regulatory role. Since the immune cells are
      capable of producing NPY upon appropriate stimulation, this peptide can regulate
      immune cell functions in an autocrine/paracrine manner. NPY also has important
      implications in several immune-mediated disorders, which affirms the clear need
      for further investigation of its role in either the mechanisms of the disease
      development or its possible therapeutic capacity. This review summarises the key
      points of NPY's mission throughout the immune system.

PMID- 22143433
TI  - Probing solution behaviour of metallosupramolecular complexes using pyrene
      fluorescence.
AB  - A new method for assessing the topology of metallosupramolecular assemblies using
      pyrene-appended ligands is reported. Two potentially tetradentate ligands
      containing one (L(1)) and two (L(2)) terminal pyrene moieties were synthesised
      and their complexes with Cu(+) and Cd(2+) were characterised. Photophysical
      measurements demonstrate that in [Cu(2)(L(1))(2)](2+), [CdL(1)](2+) and
      [Cu(2)(L(2))(2)](2+) the emission spectra are dominated by monomeric emission but
      in the cadmium complex of L(2) (where the pyrene units are in close proximity) a
      quenching of the luminescence coupled with weak emission at 540 nm is indicative
      of excimer formation.

PMID- 22143432
TI  - Beta-alanine (CarnosynTM) supplementation in elderly subjects (60-80 years):
      effects on muscle carnosine content and physical capacity.
AB  - The aim of this study was to investigate the effects of beta-alanine
      supplementation on exercise capacity and the muscle carnosine content in elderly
      subjects. Eighteen healthy elderly subjects (60-80 years, 10 female and 4 male)
      were randomly assigned to receive either beta-alanine (BA, n=12) or placebo (PL,
      n=6) for 12 weeks. The BA group received 3.2 g of beta-alanine per day (2*800 mg
      sustained-release CarnosynTM tablets, given 2 times per day). The PL group
      received 2* (2*800 mg) of a matched placebo. At baseline (PRE) and after 12 weeks
      (POST-12) of supplementation, assessments were made of the muscle carnosine
      content, anaerobic exercise capacity, muscle function, quality of life, physical
      activity and food intake. A significant increase in the muscle carnosine content
      of the gastrocnemius muscle was shown in the BA group (+85.4%) when compared with
      the PL group (+7.2%) (p=0.004; ES: 1.21). The time-to-exhaustion in the constant
      load submaximal test (i.e., TLIM) was significantly improved (p=0.05; ES: 1.71)
      in the BA group (+36.5%) versus the PL group (+8.6%). Similarly, time-to
      exhaustion in the incremental test was also significantly increased (p=0.04; ES
      1.03) following beta-alanine supplementation (+12.2%) when compared with placebo
      (+0.1%). Significant positive correlations were also shown between the relative
      change in the muscle carnosine content and the relative change in the time-to
      exhaustion in the TLIM test (r=0.62; p=0.01) and in the incremental test (r=0.48;
      p=0.02). In summary, the current data indicate for the first time, that beta
      alanine supplementation is effective in increasing the muscle carnosine content
      in healthy elderly subjects, with subsequent improvement in their exercise
      capacity.

PMID- 22143434
TI  - Recurrent Aspergillus contamination in a biomedical research facility: a case
      study.
AB  - Fungal contamination of biomedical processes and facilities can result in major
      revenue loss and product delay. A biomedical research facility (BRF) culturing
      human cell lines experienced recurring fungal contamination of clean room
      incubators over a 3-year period. In 2010, as part of the plan to mitigate
      contamination, 20 fungal specimens were isolated by air and swab samples at
      various locations within the BRF. Aspergillus niger and Aspergillus fumigatus
      were isolated from several clean-room incubators. A. niger and A. fumigatus were
      identified using sequence comparison of the 18S rRNA gene. To determine whether
      the contaminant strains isolated in 2010 were the same as or different from
      strains isolated between 2007 and 2009, a novel forensic approach to random
      amplified polymorphic DNA (RAPD) PCR was used. The phylogenetic relationship
      among isolates showed two main genotypic clusters, and indicated the continual
      presence of the same A. fumigatus strain in the clean room since 2007. Biofilms
      can serve as chronic sources of contamination; visual inspection of plugs within
      the incubators revealed fungal biofilms. Moreover, confocal microscopy imaging of
      flow cell-grown biofilms demonstrated that the strains isolated from the
      incubators formed dense biofilms relative to other environmental isolates from
      the BRF. Lastly, the efficacies of various disinfectants employed at the BRF were
      examined for their ability to prevent spore germination. Overall, the
      investigation found that the use of rubber plugs around thermometers in the
      tissue culture incubators provided a microenvironment where A. fumigatus could
      survive regular surface disinfection. A general lesson from this case study is
      that the presence of microenvironments harboring contaminants can undermine
      decontamination procedures and serve as a source of recurrent contamination.

PMID- 22143435
TI  - Effects of Tween 80 and pH on mycelial pellets and exopolysaccharide production
      in liquid culture of a medicinal fungus.
AB  - This study investigated the effects of surfactant additives and medium pH on
      mycelial morphology and exopolysaccharide (EPS) production in liquid culture of a
      valuable medicinal fungus Cordyceps sinensis Cs-HK1. In the medium containing 20
      g l-1 glucose and 6 g l-1 peptone as the sole nitrogen source, the Cs-HK1 fungal
      mycelia formed smooth and spherical pellets about 1.8-mm mean diameter. The
      mycelial pellets became less uniform at pH (4.0-5.0) lower than the optimum (pH
      6.0) or turned to filamentous form at higher pH (8-9). Surfactants added to the
      medium inhibited pellet formation, resulting in smaller and looser pellets. Tween
      80 exhibited a remarkable promoting effect on EPS production, increasing the EPS
      yield more than twofold at 1.5% (w/v), which was most probably attributed to the
      stimulation of EPS biosynthesis and release from the fungal cells by Tween 80.

PMID- 22143436
TI  - Informed consent and decision-making about adult-to-adult living donor liver
      transplantation: a systematic review of empirical research.
AB  - Adult-to-adult living donor liver transplantation (LDLT) is a complex procedure
      that poses serious health risks to and provides no direct health benefit for the
      donor. Because of this uneven risk-benefit ratio, ensuring donor autonomy through
      informed consent is critical. To assess the current knowledge pertaining to
      informed consent for LDLT, we conducted a systematic review of the empirical
      literature on donors' decision-making process, comprehension about risks and
      outcomes, and information needs for LDLT. Of the 1423 identified articles, 24 met
      final review criteria, representing the perspective of approximately 2789
      potential and actual donors. As donors' decisions to donate often occur before
      evaluation, they often make uninformed decisions. The review found that 88% to
      95% of donors reported understanding information clinicians disclosed about risks
      and benefits. However, donors reported unmet information needs, knowledge gaps
      regarding risks, and unanticipated complications. Few donors reported feeling
      pressure to donate. Most studies were limited by cultural differences, small
      sample sizes, inconsistent measures, and poor methodological approaches. This
      systematic review suggests that informed consent for LDLT is sub-optimal as
      donors do not adequately appreciate disclosed information during the informed
      consent process, despite United Network for Organ Sharing/CMS regulations
      requiring formal psychological evaluation of donor candidates. Interventions are
      needed to improve donor-clinician communication during the LDLT informed consent
      process such as through the use of comprehension assessment tools and e-health
      educational tools that leverage adult learning theory to effectively convey LDLT
      outcome data.

PMID- 22143439
TI  - Magnetically gated microelectrodes.
AB  - Microelectrodes fabricated in the center of single-coil microelectromagnetic
      traps are described. Magnetic particles are then used to reversibly gate
      transport of an electroactive species to the surface of the electrode or as a
      means to produce an ON/OFF bioelectrocatalytic glucose sensor.

PMID- 22143437
TI  - Prediction of metalloproteinase family based on the concept of Chou's pseudo
      amino acid composition using a machine learning approach.
AB  - Matrix metalloproteinase (MMPs) and disintegrin and metalloprotease (ADAMs)
      belong to the zinc-dependent metalloproteinase family of proteins. These proteins
      participate in various physiological and pathological states. Thus, prediction of
      these proteins using amino acid sequence would be helpful. We have developed a
      method to predict these proteins based on the features derived from Chou's pseudo
      amino acid composition (PseAAC) server and support vector machine (SVM) as a
      powerful machine learning approach. With this method, for ADAMs and MMPs
      families, an overall accuracy and Matthew's correlation coefficient (MCC) of
      95.89 and 0.90% were achieved respectively. Furthermore, the method is able to
      predict two major subclasses of MMP family; Furin-activated secreted MMPs and
      Type II trans-membrane; with MCC of 0.89 and 0.91%, respectively. The overall
      accuracy for Furin-activated secreted MMPs and Type II trans-membrane was 98.18
      and 99.07, respectively. Our data demonstrates an effective classification of
      Metalloproteinase family based on the concept of PseAAC and SVM.

PMID- 22143440
TI  - Current world literature.

PMID- 22143442
TI  - Influence of acclimation temperature on the induction of heat-shock protein 70 in
      the catfish Horabagrus brachysoma (Gunther).
AB  - Every organism responds to heat stress by synthesizing a group of evolutionarily
      conserved proteins called the heat-shock proteins (HSPs) that, by acting as
      molecular chaperones, protect the cell against the aggregation of denatured
      proteins and play a significant role in adaptation to temperature. The present
      study aimed to investigate the critical thermal maxima (CTMax) and the expression
      of HSP70 in different tissues (gill, brain, muscle and liver) of an endemic
      catfish Horabagrus brachysoma acclimated at either 20 or 30 degrees C for 30
      days. To understand the HSP70 response, fish acclimated to the two temperatures
      were exposed to preset temperatures (26, 30, 34, 36 and 38 degrees C for 20
      degrees C acclimated fish and 32, 34, 36, 38 and 40 degrees C for 30 degrees C
      acclimated fish) for 2 h, followed by 1 h recovery at their respective
      acclimation temperatures. The HSP70 levels in the gill, brain, muscle and liver
      tissues were determined by Western blotting of one-dimensional sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis. A significant (P < 0.05) increase in
      the CTMax values was observed for fish acclimated at 30 degrees C (41.86 +/- 0.39
      degrees C) than those acclimated at 20 degrees C (39.13 +/- 0.18 degrees C).
      HSP70 was detected in all the tissues with the highest level in the liver
      followed by intermediate levels in muscle and brain, and lowest level in gill
      tissue, irrespective of the acclimation temperatures (20 or 30 degrees C). The
      HSP70 levels were significantly higher (P < 0.05) in the tissues of fish
      acclimated at 30 degrees C than those acclimated at 20 degrees C. The mean
      induction temperature of HSP70 in all the tissues of fish acclimated at either 20
      or 30 degrees C was 30 and 34 degrees C, respectively. The optimum temperature
      for HSP70 induction in all the tissues of fish acclimated at 20 degrees C was 36
      degrees C, whereas for fish acclimated at 30 degrees C was 36 degrees C for gill
      and 38 degrees C for brain, muscle and liver. Decreased levels of HSP70 were
      noted in all the tissues of fish when exposed to temperatures that exceeded the
      optimum temperatures for HSP70 inductions. Overall results indicated that
      acclimation temperature influences both temperature tolerance and induction of
      HSP70 in H. brachysoma.

PMID- 22143443
TI  - Infant monkeys' concept of animacy: the role of eyes and fluffiness.
AB  - Both human and nonhuman primates have been suggested to possess some essential
      knowledge about animate entities, but it remains unclear whether the concept of
      animacy is shared across species, which properties are used as an "animacy
      marker," and whether such ability is present at birth. We investigated infant
      Japanese monkeys' looking responses towards novel objects varying in both
      physical appearance and self-propelled motion, with the aim of depicting the role
      of eyes and fluffiness in the early recognition of animacy. Presented with an
      inanimate natural stone, three-month-old monkeys showed longer looking times at
      the stone's self-propelled motion than at its baseline still posture. This effect
      became significantly smaller when artificial fur was attached to the stone, while
      adding artificial eyes did not elicit a departing pattern in their looking
      behavior. In contrast, one-month-old monkeys showed no systematic differences in
      their looking behavior. This suggests that the concept of animacy in terms of
      self-propelledness may develop between one and three months of age, with
      sensitivity to texture emerging by three months. Development of biological
      knowledge is discussed in relation to social knowledge from both ontogenetic and
      phylogenetic perspectives.

PMID- 22143445
TI  - [Hypoxia is a key factor in the inflammatory milieu of rheumatic diseases].
AB  - Chronic inflammatory diseases are characterized by hypoxia and subsequent
      cellular adaptation via hypoxia-inducible factor (HIF). Modulation of these
      adaptation mechanisms provides the basis for ideas on how to improve the effects
      of known drugs and for the development of novel therapeutic approaches.

PMID- 22143444
TI  - Determining the phagocytic activity of clinical antibody samples.
AB  - Antibody-driven phagocytosis is induced via the engagement of Fc receptors on
      professional phagocytes, and can contribute to both clearance as well as
      pathology of disease. While the properties of the variable domains of antibodies
      have long been considered critical to in vivo function, the ability of antibodies
      to recruit innate immune cells via their Fc domains has become increasingly
      appreciated as a major factor in their efficacy, both in the setting of
      recombinant monoclonal antibody therapy, as well as in the course of natural
      infection or vaccination(1-3). Importantly, despite its nomenclature as a
      constant domain, the antibody Fc domain does not have constant function, and is
      strongly modulated by IgG subclass (IgG1-4) and glycosylation at Asparagine 297(4
      6).  Thus, this method to study functional differences of antigen-specific
      antibodies in clinical samples will facilitate correlation of the phagocytic
      potential of antibodies to disease state, susceptibility to infection,
      progression, or clinical outcome. Furthermore, this effector function is
      particularly important in light of the documented ability of antibodies to
      enhance infection by providing pathogens access into host cells via Fc receptor
      driven phagocytosis(7).  Additionally, there is some evidence that phagocytic
      uptake of immune complexes can impact the Th1/Th2 polarization of the immune
      response(8). Here, we describe an assay designed to detect differences in
      antibody-induced phagocytosis, which may be caused by differential IgG subclass,
      glycan structure at Asn297, as well as the ability to form immune complexes of
      antigen-specific antibodies in a high-throughput fashion.  To this end, 1 MUm
      fluorescent beads are coated with antigen, then incubated with clinical antibody
      samples, generating fluorescent antigen specific immune complexes.  These
      antibody-opsonized beads are then incubated with a monocytic cell line expressing
      multiple FcgammaRs, including both inhibitory and activating. Assay output can
      include phagocytic activity, cytokine secretion, and patterns of FcgammaRs usage,
      and are determined in a standardized manner, making this a highly useful system
      for parsing differences in this antibody-dependent effector function in both
      infection and vaccine-mediated protection(9).

PMID- 22143446
TI  - Development and external validation of a nomogram for predicting cancer
      probability at initial prostate biopsy using the life expectancy- and prostate
      volume-adjusted biopsy scheme.
AB  - BACKGROUND: We previously reported the diagnostic efficacy of the age- and
      prostate volume-adjusted prostate biopsy method (the adjusted biopsy method).
      Here, we developed a new nomogram for predicting cancer probability at initial
      biopsy using the adjusted method. METHODS: Between 2002 and 2010, 1059 Japanese
      men with PSA levels between 1.1 and 40 ng ml(-1) and biopsied for the first time
      using the adjusted method at Gunma University Hospital were enrolled. All
      subjects underwent digital rectal examination (DRE) and transrectal
      ultrasonography (TRUS). Data from the initial 849 subjects were used for
      development of the nomogram and those from the final 210 subjects were used for
      internal validation. External validation was conducted using data from two
      affiliated hospitals where the same adjusted biopsy method was used. The nomogram
      was developed through logistic regression analysis, and predictive accuracy and
      performance characteristics were assessed using the area under the curve (AUC) of
      the receiver operating characteristics and calibration plots. Furthermore, we
      compared the predictive accuracy of the newly developed nomogram with the
      'Prostate Risk Indicator' using the development data set, as well as the two
      external data sets. RESULTS: The AUC of the logistic regression-based nomogram
      was significantly higher than those of any single clinical parameter. External
      validation showed significant correlations with the present model. The AUC
      receiver operating characteristic of the 'Prostate Risk Indicator' was the second
      largest following the new nomogram using the development data set and one
      external data set and almost equal to the new nomogram using the other external
      data set. CONCLUSIONS: Nevertheless the present model does not include somewhat
      subjective findings on TRUS abnormality, which is necessary for the estimation by
      'Prostate Risk Indicator', the predictive accuracy of the present simple nomogram
      could be excellent enough to contribute to accurate shared decision-making
      between doctors and men who are candidates for the adjusted biopsy scheme.

PMID- 22143447
TI  - Active surveillance for low-risk prostate cancer: knowledge, acceptance and
      practice among urologists.
AB  - BACKGROUND: This study aimed to survey urologists regarding their knowledge,
      acceptance and practice of active surveillance (AS) for low-risk prostate cancer.
      METHODS: An email-based survey was distributed to 4987 urologists. Respondents
      were surveyed regarding their knowledge and acceptance of AS. Those who felt AS
      was a reasonable strategy were asked their opinions on the criteria for AS
      enrollment and the details of their practice of AS. Respondents who felt AS was
      not a reasonable alternative were queried as to the reasons why. RESULTS: A total
      of 425 (9%) urologists successfully completed the survey and 387 (91%) were both
      familiar with AS and aware that AS differed from watchful waiting. Of this latter
      group, 370 (96%) respondents felt AS was a reasonable management strategy, 95% of
      whom manage patients with this approach. A minority of respondents (6%) felt that
      patients with a PSA>10 ng ml(-1) were eligible for AS. Further, most participants
      (74%) felt that patients required a Gleason score <=6. There was little agreement
      on the timing of follow-up biopsies. Respondents who objected to AS were most
      commonly concerned with missing an opportunity for curative treatment (76%) and
      the risk of tumor undergrading (65%). CONCLUSIONS: The majority of participants
      were knowledgeable and accepting of AS. Respondents were in relative agreement
      regarding the PSA and Gleason score criteria for AS enrollment. In contrast,
      there was a lack of agreement on the timing of follow-up biopsies. In the future,
      comparative studies are required to determine the optimal enrollment criteria and
      follow-up protocol for patients managed with AS.

PMID- 22143448
TI  - Medium-term clinical outcomes following surgical repair for vaginal prolapse with
      tension-free mesh and vaginal support device.
AB  - INTRODUCTION AND HYPOTHESIS: This study was designed to evaluate clinical
      outcomes >=2 years following surgery with polypropylene mesh and vaginal support
      device (VSD) in women with vaginal prolapse, in a prospective, multi-center
      setting. METHODS: Patients re-consented for this extended follow-up (n = 110),
      with anatomic evaluation using Pelvic Organ Prolapse Quantification (POP-Q) and
      validated questionnaires to assess pelvic symptoms and sexual function.
      Complications were recorded (safety set; n = 121). RESULTS: Median length of
      follow-up was 29 months (range 24-34 months). The primary anatomic success,
      defined as POP-Q 0-I, was 69.1%; however, in 84.5% of the cases, the leading
      vaginal edge was above the hymen. Pelvic symptoms and sexual function improved
      significantly from baseline (p < 0.01). Mesh exposure rate was 9.1%. Five percent
      reported stress urinary incontinence and 3.3% required further prolapse surgery.
      CONCLUSION: These results indicate this non-anchored mesh repair is a safe and
      effective treatment for women with symptomatic vaginal prolapse in the medium
      term.

PMID- 22143449
TI  - Midurethral sling shortening for persistent stress urinary incontinence.
AB  - We describe techniques and objective and subjective outcomes for women who
      underwent midurethral sling (MUS) shortening for persistent stress urinary
      incontinence (SUI). This is a case series of women who underwent MUS shortening
      for SUI within 8 weeks of initial MUS placement. Objective and subjective
      findings including Urinary Distress Inventory (UDI)-6 and Urinary Impact
      Questionnaire (UIQ)-7 scores are reported, and shortening techniques are
      described. Between June 2007 and June 2010, three women underwent MUS shortening
      for persistent SUI within 8 weeks of initial MUS placement. Shortening was
      performed with either midline plication or mesh excision and reapproximation.
      Five months postoperative to shortening, one woman reported subjective
      improvement in SUI symptoms, and two had subjective and objective resolution of
      SUI. All showed improvement from baseline in UDI-6 and UIQ-7 scores. There were
      no erosions. MUS shortening may offer a safe and effective option for management
      of persistent SUI.

PMID- 22143450
TI  - Risk factors for obstetric fistula: a clinical review.
AB  - Obstetric fistula is the presence of a hole between a woman's genital tract and
      either the urinary or the intestinal tract. Better knowledge of the risk factors
      for obstetric fistula could help in preventing its occurrence. The purpose of
      this study was to assess the characteristics of obstetric fistula patients. We
      conducted a search of the literature to identify all relevant articles published
      during the period from 1987-2008. Among the 19 selected studies, 15 were reports
      from sub-Saharan Africa and 4 from the Middle East. Among the reported fistula
      cases, 79.4% to 100% were obstetrical while the remaining cases were from other
      causes. Rectovaginal fistulae accounted for 1% to 8%, vesicovaginal fistulae for
      79% to 100% of cases, and combined vesicovaginal and rectovaginal fistulae were
      reported in 1% to 23% of cases. Teenagers accounted for 8.9% to 86% of the
      obstetrical fistulae patients at the time of treatment. Thirty-one to 67% of
      these women were primiparas. Among the obstetric fistula patients, 57.6% to 94.8%
      of women labor at home and are secondarily transferred to health facilities. Nine
      to 84% percent of these women delivered at home. Many of the fistula patients
      were shorter than 150 cm tall (40-79.4%). The mean duration of labor among the
      fistula patients ranged from 2.5 to 4 days. Twenty to 95.7% of patients labored
      for more than 24 h. Operative delivery was eventually performed in 11% to 60% of
      cases. Obstetric fistula was associated with several risk factors, and they
      appear to be preventable. This knowledge should be used in strengthening the
      preventive strategy both at the health facility and at the community level.

PMID- 22143451
TI  - Concurrent vesicoperitoneal and vesicovaginal fistulae.
AB  - Although rare in the USA, vesicovaginal fistulae are usually associated with
      postoperative complications. Even more rarely seen, vesicoperitoneal fistulae can
      also present postoperatively. Both types of fistulae pose as diagnostically
      challenging and can be difficult to manage. We describe a case report of a
      patient with both vesicovaginal and vesicoperitoneal fistulae after a
      laparoscopic-assisted vaginal hysterectomy who presented with abdominal pain and
      anuria. Cystogram and outpatient cystoscopy were imperative in the diagnosis. She
      was conservatively managed with continuous bladder drainage via indwelling
      catheter resulting in an ideal recovery without requiring reoperation.

PMID- 22143452
TI  - Nurse-led disease management for hypertension control in a diverse urban
      community: a randomized trial.
AB  - BACKGROUND: Treated but uncontrolled hypertension is highly prevalent in African
      American and Hispanic communities. OBJECTIVE: To test the effectiveness on blood
      pressure of home blood pressure monitors alone or in combination with follow-up
      by a nurse manager. DESIGN: Randomized controlled effectiveness trial. PATIENTS:
      Four hundred and sixteen African American or Hispanic patients with a history of
      uncontrolled hypertension. Patients with blood pressure >=150/95, or >=140/85 for
      patients with diabetes or renal disease, at enrollment were recruited from one
      community clinic and four hospital outpatient clinics in East and Central Harlem,
      New York City. INTERVENTION: Patients were randomized to receive usual care or a
      home blood pressure monitor plus one in-person counseling session and 9 months of
      telephone follow-up with a registered nurse. During the trial, the home monitor
      alone arm was added. MAIN MEASURES: Change in systolic and diastolic blood
      pressure at 9 and 18 months. KEY RESULTS: Changes from baseline to 9 months in
      systolic blood pressure relative to usual care was -7.0 mm Hg (Confidence
      Interval [CI], -13.4 to -0.6) in the nurse management plus home blood pressure
      monitor arm, and +1.1 mm Hg (95% CI, -5.5 to 7.8) in the home blood pressure
      monitor only arm. No statistically significant differences in systolic blood
      pressure were observed among treatment arms at 18 months. No statistically
      significant improvements in diastolic blood pressure were found across treatment
      arms at 9 or 18 months. Changes in prescribing practices did not explain the
      decrease in blood pressure in the nurse management arm. CONCLUSIONS: A nurse
      management intervention combining an in-person visit, periodic phone calls, and
      home blood pressure monitoring over 9 months was associated with a statistically
      significant reduction in systolic, but not diastolic, blood pressure compared to
      usual care in a high risk population. Home blood pressure monitoring alone was no
      more effective than usual care.

PMID- 22143453
TI  - A 60-year-old woman with chorea and weight loss.

PMID- 22143454
TI  - Non-verbal communication between primary care physicians and older patients: how
      does race matter?
AB  - BACKGROUND: Non-verbal communication is an important aspect of the diagnostic and
      therapeutic process, especially with older patients. It is unknown how non-verbal
      communication varies with physician and patient race. OBJECTIVE: To examine the
      joint influence of physician race and patient race on non-verbal communication
      displayed by primary care physicians during medical interviews with patients 65
      years or older. DESIGN, SETTING, AND PARTICIPANTS: Video-recordings of visits of
      209 patients 65 years old or older to 30 primary care physicians at three clinics
      located in the Midwest and Southwest. MAIN MEASURES: Duration of physicians' open
      body position, eye contact, smile, and non-task touch, coded using an adaption of
      the Nonverbal Communication in Doctor-Elderly Patient Transactions form. KEY
      RESULTS: African American physicians with African American patients used more
      open body position, smile, and touch, compared to the average across other dyads
      (adjusted mean difference for open body position = 16.55, p < 0.001; smile =
      2.35, p = 0.048; touch = 1.33, p < 0.001). African American physicians with white
      patients spent less time in open body position compared to the average across
      other dyads, but they also used more smile and eye gaze (adjusted mean difference
      for open body position = 27.25, p < 0.001; smile = 3.16, p = 0.005; eye gaze =
      17.05, p < 0.001). There were no differences between white physicians' behavior
      toward African American vs. white patients. CONCLUSION: Race plays a role in
      physicians' non-verbal communication with older patients. Its influence is best
      understood when physician race and patient race are considered jointly.

PMID- 22143456
TI  - Spin echo NMR spectra without J modulation.
AB  - The spin echo is the single most important building block in modern NMR
      spectroscopy, but echo modulation by scalar couplings J can severely complicate
      its use. We show for the first time that a general but unacknowledged solution to
      such complications already exists.

PMID- 22143455
TI  - Preventing hospital-acquired infections: a national survey of practices reported
      by U.S. hospitals in 2005 and 2009.
AB  - BACKGROUND: Hospital-acquired infection (HAI) is common, costly, and potentially
      lethal. Whether initiatives to reduce HAI--such as the Centers for Medicare and
      Medicaid Services (CMS) no payment rule--have increased the use of preventive
      practices is not known. OBJECTIVE: To examine the use of infection prevention
      practices by U.S. hospitals and trends in use between 2005 and 2009. DESIGN,
      SETTING, AND PARTICIPANTS: Surveys of infection preventionists at non-federal
      general medical/surgical hospitals and Department of Veterans Affairs (VA)
      hospitals, which are not subject to the CMS no payment rule, in 2005 and 2009.
      MAIN MEASURES: Percent of hospitals using practices to prevent central line
      associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP),
      and catheter-associated urinary tract infection (CAUTI). KEY RESULTS: Survey
      response was approximately 70%. More than 1/2 of non-federal hospitals reported a
      moderate or large increase in CLABSI, VAP and CAUTI prevention as a facility
      priority due to the non-payment rule; over 60% of VA hospitals reported no change
      in priority. However, both non-federal and VA hospitals reported significant
      increases in use of most practices to prevent CLABSI, VAP and CAUTI from 2005 to
      2009, with 90% or more using certain practices to prevent CLABSI and VAP in 2009.
      In contrast, only one CAUTI prevention practice was used by at least 50% of
      hospitals. CONCLUSIONS: Since 2005, use of key practices to prevent CLABSI, VAP
      and CAUTI has increased in non-federal and VA hospitals, suggesting that despite
      its perceived importance, the non-payment rule may not be the primary driver.
      Moreover, while 65% of non-federal hospitals reported a moderate or large
      increase in preventing CAUTI as a facility priority, prevention practice use
      remains low.

PMID- 22143457
TI  - Improving the performance of a poorly adsorbing porous material: template
      mediated addition of microporosity to a crystalline submicroporous MOF.
AB  - The presence of butanoic acid excess in the reaction media employed for the
      synthesis of a MOF with formula [Cu(2)(MU(3)-ade)(2)(MU(2)
      OOC(CH(2))(2)CH(3))(2)](n) (ade: adeninate) leads to the formation of micelles
      that exert a template effect and provide a pronounced increase of its
      microporosity, doubling the intrinsic adsorption capacity of the pristine crystal
      network.

PMID- 22143458
TI  - High-density genetic and physical bin mapping of wheat chromosome 1D reveals that
      the powdery mildew resistance gene Pm24 is located in a highly recombinogenic
      region.
AB  - Genetic maps of wheat chromosome 1D consisting of 57 microsatellite marker loci
      were constructed using Chinese Spring (CS) * Chiyacao F(2) and the International
      Triticeae Mapping Initiative (ITMI) recombinant inbred lines (RILs) mapping
      populations. Marker order was consistent, but genetic distances of neighboring
      markers were different in two populations. Physical bin map of 57 microsatellite
      marker loci was generated by means of 10 CS 1D deletion lines. The physical bin
      mapping indicated that microsatellite marker loci were not randomly distributed
      on chromosome 1D. Nineteen of the 24 (79.2%) microsatellite markers were mapped
      in the distal 30% genomic region of 1DS, whereas 25 of the 33 (75.8%) markers
      were assigned to the distal 59% region of 1DL. The powdery mildew resistance gene
      Pm24, originating from the Chinese wheat landrace Chiyacao, was previously mapped
      in the vicinity of the centromere on the short arm of chromosome 1D. A high
      density genetic map of chromosome 1D was constructed, consisting of 36 markers
      and Pm24, with a total map length of 292.7 cM. Twelve marker loci were found to
      be closely linked to Pm24. Pm24 was flanked by Xgwm789 (Xgwm603) and Xbarc229
      with genetic distances of 2.4 and 3.6 cM, respectively, whereas a microsatellite
      marker Xgwm1291 co-segregated with Pm24. The microsatellite marker Xgwm1291 was
      assigned to the bin 1DS5-0.70-1.00 of the chromosome arm 1DS. It could be
      concluded that Pm24 is located in the '1S0.8 gene-rich region', a highly
      recombinogenic region of wheat. The results presented here would provide a start
      point for the map-based cloning of Pm24.

PMID- 22143459
TI  - Incidence, diagnosis, and treatment of chylous leakage after laparoscopic live
      donor nephrectomy.
AB  - BACKGROUND: Chylous leakage (CL) is a rare complication of laparoscopic live
      donor nephrectomy (LLDN). It may lead to malnutrition and immunological deficits
      because of protein and lymphocyte depletion. METHODS: Data from 208 consecutive
      LLDN performed at two institutions, between April 2000 and September 2010, were
      reviewed to identify the anatomical basis behind CL along with its diagnostic and
      therapeutic options. RESULTS: CL developed in eight donors (3.8%), as determined
      by high-volume drainage (range 540-800 mL/24 hr) of triglyceride-rich fluid. All
      donors were managed conservatively. Seven were put on total parenteral nutrition
      plus octreotide. One received low-fat diet, medium-chain triglyceride
      supplementation, and octreotide. Chylous fistulas resolved in 5 to 16 days (mean
      time 12.3 days). Drains were removed before hospital discharge, and no donor was
      readmitted and/or needed outpatient care. CONCLUSIONS: CL is a potentially
      insidious and perhaps misdiagnosed complication after LLDN. It occurs in nearly
      4% of LLDN and it seems to be uniquely associated to left-sided kidney recovery
      because of distinctive lymphatics distribution around the periaortic area of
      dissection. Conservative therapy is effective in most donors and should be
      initially attempted. Surgical ligatures or fibrin sealants may be indicated in
      case of refractory CL before the arising of malnutrition and/or relevant
      immunodeficiency.

PMID- 22143460
TI  - p53 negatively regulates the osteogenic differentiation of vascular smooth muscle
      cells in mice with chronic kidney disease.
AB  - AIM: To investigate the osteogenic differentiation of vascular smooth muscle
      cells (VSMCs) in mice with chronic kidney disease (CKD) and to evaluate the
      effects of p53 on the osteogenic differentiation of the VSMCs. METHODS:
      Experimental models of CKD-associated vascular calcification generated by five
      sixth (5/6) nephrectomy (Nx) and a high-phosphate (HP) diet were used in p53+/+
      and p53-/- mice. Following 5/6 Nx, aortic calcification, markers of osteogenic
      differentiation, VSMCs and p53 protein in aortic tissues were studied. RESULTS:
      Aortic calcification was observed after eight weeks following 5/6 Nx in mice of
      both genotypes, and expression of the markers of osteogenic differentiation in
      the VSMCs was increased. These changes were continuously observed up to 12 weeks
      after 57/6 Nx, and particularly after 5/6 Nx + HP. Compared with p53+/+ mice,
      aortic calcification in p53-/- mice was more severe (p < 0.001). Expression of
      the markers of osteogenic differentiation was noticeably increased (p < 0.001),
      while expression of the marker of VSMCs had decreased (p < 0.001). Statistical
      analysis demonstrated that the markers of osteogenic differentiation were
      negatively correlated with p53, and the marker of VSMCs was positively correlated
      with p53 (p < 0.001). CONCLUSION: p53 has the potential to negatively regulate
      the osteogenic differentiation of VSMCs in CKD mice.

PMID- 22143461
TI  - Amide hydrogen/deuterium exchange & MALDI-TOF mass spectrometry analysis of Pak2
      activation.
AB  - Amide hydrogen/deuterium exchange (H/D exchange) coupled with mass spectrometry
      has been widely used to analyze the interface of protein-protein interactions,
      protein conformational changes, protein dynamics and protein-ligand interactions.
      H/D exchange on the backbone amide positions has been utilized to measure the
      deuteration rates of the micro-regions in a protein by mass spectrometry(1,2,3).
      The resolution of this method depends on pepsin digestion of the deuterated
      protein of interest into peptides that normally range from 3-20 residues.
      Although the resolution of H/D exchange measured by mass spectrometry is lower
      than the single residue resolution measured by the Heteronuclear Single Quantum
      Coherence (HSQC) method of NMR, the mass spectrometry measurement in H/D exchange
      is not restricted by the size of the protein(4). H/D exchange is carried out in
      an aqueous solution which maintains protein conformation. We provide a method
      that utilizes the MALDI-TOF for detection(2), instead of a HPLC/ESI (electrospray
      ionization)-MS system(5,6). The MALDI-TOF provides accurate mass intensity data
      for the peptides of the digested protein, in this case protein kinase Pak2 (also
      called gamma-Pak). Proteolysis of Pak 2 is carried out in an offline pepsin
      digestion. This alternative method, when the user does not have access to a HPLC
      and pepsin column connected to mass spectrometry, or when the pepsin column on
      HPLC does not result in an optimal digestion map, for example, the heavily
      disulfide-bonded secreted Phospholipase A(2;) (sPLA(2;)). Utilizing this method,
      we successfully monitored changes in the deuteration level during activation of
      Pak2 by caspase 3 cleavage and autophosphorylation(7,8,9).

PMID- 22143462
TI  - An aptamer-based keypad lock system.
AB  - An aptamer-based security system mimicking keypad lock function was successfully
      designed. The system was turned "ON" with a strong fluorescent output signal only
      when the inputs were added according to the correct combination and exact
      sequence. Otherwise, the system was kept "OFF" to prevent illegal access.

PMID- 22143463
TI  - The coupling of localized surface plasmon resonance-based photoelectrochemistry
      and nanoparticle size effect: towards novel plasmonic photoelectrochemical
      biosensing.
AB  - Visible light-activated localized surface plasmon resonance-based
      photoelectrochemical detection is reported for the first time.

PMID- 22143465
TI  - Factors associated with a medical home among children with Attention-Deficit
      Hyperactivity Disorder.
AB  - Providing a medical home to children with Attention-Deficit Hyperactivity
      Disorder (ADHD) is challenging. Little is known about the factors associated with
      having a medical home for these children, or how comorbidities affect having a
      medical home. Our study aims are: (1) identify factors associated with having a
      medical home and five sub-components of a medical home and (2) determine the
      effect of medical home on several outcomes for children with ADHD. The sample
      included 5,495 children with ADHD from the 2007 National Survey of Children's
      Health. Descriptive and multivariate analyses were conducted. Children with ADHD
      alone and children with ADHD plus a physical diagnosis had greater frequencies of
      having a medical home, or meeting the five sub-components, than children with
      ADHD plus a mental diagnosis. Multivariate results show that children with ADHD
      plus a physical and/or mental comorbidity were 24-63% more likely to be without a
      medical home compared to children with only ADHD. Having a medical home also had
      a bearing on several child health outcomes. Having a medical home was
      significantly associated with being less likely to have an unmet health need and
      having fewer missed school days; but also being less likely to have received
      needed mental health care (P < .05). Our results suggest that there are
      differences in parent's perceptions of receiving care among children with ADHD.
      Pediatric medical home projects and policies should acknowledge that children
      with ADHD often have comorbidities making their care more complex. These
      complexities should be addressed during practice transformation and setting
      reimbursement policies.

PMID- 22143466
TI  - Geographic variation in trends and characteristics of teen childbearing among
      American Indians and Alaska Natives, 1990-2007.
AB  - To study teen birth rates, trends, and socio-demographic and pregnancy
      characteristics of AI/AN across geographic regions in the US. The birth rate for
      US teenagers 15-19 years reached a historic low in 2009 (39.1 per 1,000) and yet
      remains one of the highest teen birth rates among industrialized nations. In the
      US, teen birth rates among Hispanic, non-Hispanic black, and American
      Indian/Alaska Native (AI/AN) youth are consistently two to three times the rate
      among non-Hispanic white teens. Birth certificate data for females younger than
      age 20 were used to calculate birth rates (live births per 1,000 women) and
      joinpoint regression to describe trends in teen birth rates by age (<15, 15-17,
      18-19) and region (Aberdeen, Alaska, Bemidji, Billings, California, Nashville,
      Oklahoma, Portland, Southwest). Birth rates for AI/AN teens varied across
      geographic regions. Among 15-19-year-old AI/AN, rates ranged from 24.35
      (California) to 123.24 (Aberdeen). AI/AN teen birth rates declined from the early
      1990s into the 2000s for all three age groups. Among 15-17-year-olds, trends were
      approximately level during the early 2000s-2007 in six regions and declined in
      the others. Among 18-19-year-olds, trends were significantly increasing during
      the early 2000s-2007 in three regions, significantly decreasing in one, and were
      level in the remaining regions. Among AI/AN, cesarean section rates were lower in
      Alaska (4.1%) than in other regions (16.4-26.6%). This is the first national
      study to describe regional variation in AI/AN teen birth rates. These data may be
      used to target limited resources for teen pregnancy intervention programs and
      guide research.

PMID- 22143467
TI  - Paramagnetic dithiolene complexes as metallo-ligands: ether/thioether
      coordination.
AB  - The secondary coordination ability of a paramagnetic nickel dithiolene complex,
      bearing an ether coordinating function within a nine-membered flexible ring, has
      been demonstrated in its [NiCl(DMF)(2)](+) complex, through coordination by both
      ether and thioether functions, allowing for a ferromagnetic interaction between
      both paramagnetic entities.

PMID- 22143464
TI  - Bias in protein and potassium intake collected with 24-h recalls (EPIC-Soft) is
      rather comparable across European populations.
AB  - PURPOSE: We investigated whether group-level bias of a 24-h recall estimate of
      protein and potassium intake, as compared to biomarkers, varied across European
      centers and whether this was influenced by characteristics of individuals or
      centers. METHODS: The combined data from EFCOVAL and EPIC studies included 14
      centers from 9 countries (n = 1,841). Dietary data were collected using a
      computerized 24-h recall (EPIC-Soft). Nitrogen and potassium in 24-h urine
      collections were used as reference method. Multilevel linear regression analysis
      was performed, including individual-level (e.g., BMI) and center-level (e.g.,
      food pattern index) variables. RESULTS: For protein intake, no between-center
      variation in bias was observed in men while it was 5.7% in women. For potassium
      intake, the between-center variation in bias was 8.9% in men and null in women.
      BMI was an important factor influencing the biases across centers (p < 0.01 in
      all analyses). In addition, mode of administration (p = 0.06 in women) and day of
      the week (p = 0.03 in men and p = 0.06 in women) may have influenced the bias in
      protein intake across centers. After inclusion of these individual variables,
      between-center variation in bias in protein intake disappeared for women, whereas
      for potassium, it increased slightly in men (to 9.5%). Center-level variables did
      not influence the results. CONCLUSION: The results suggest that group-level bias
      in protein and potassium (for women) collected with 24-h recalls does not vary
      across centers and to a certain extent varies for potassium in men. BMI and study
      design aspects, rather than center-level characteristics, affected the biases
      across centers.

PMID- 22143468
TI  - Thrombosis in cardiovascular medicine: a review of pathophysiology, mechanisms of
      drug action, and the "alphabet" of established and emerging therapies.
AB  - Thrombosis is a physiologic hemostatic response to vascular injury. Thrombus
      generation has evolved as a complex event involving multiphasic biologic inputs
      and regulation. Pathologic thrombosis in cardiovascular medicine afflicts
      millions of U.S. citizens per year, exacting a death total in the hundreds of
      thousands of people. These morbid events are particularly common in the settings
      of trauma, major surgery, and high-risk medical patients both inside and outside
      of the hospital. The frequency of all of these risks increases as our population
      grows and ages. The discussion that follows sketches the roots of our
      understanding of pathologic thrombosis through a clinical case example, a
      highlight of the historically key concepts involved, identification of the phasic
      inputs into thrombus formation and regulation, and a listing of the therapeutics
      and agents used in treating the thrombosis "epidemic".

PMID- 22143469
TI  - Heparin-induced thrombocytopenia in the cardiac patient: 10 points to help the
      physician.
AB  - CASE 1: A 65-year-old man underwent triple coronary artery bypass surgery.
      Postoperative atrial fibrillation lengthened his ICU stay. On postoperative day
      6, it was noted that the platelet count, which had begun to rise from a
      postoperative nadir of 105,000, had fallen again to 90,000. The cardiologist
      indicated suspicion of heparin-induced thrombocytopenia (HIT); he stopped all
      heparin and ordered a heparin antibody test. Platelets were 98,000 the next day
      when the cardiologist wrote, "I am considering calling Hematology, but they would
      likely anticoagulate the patient; his stool guaiac is positive, so I will hold
      off consultation." The next morning, the patient had a pulseless, cool, and
      cyanotic right arm. On arrival, the hematologist found the patient confused, with
      a tender abdomen and absent bowel sounds. In spite of initiation of a direct
      thrombin inhibitor, the patient expired of bowel necrosis and sepsis within a few
      days. CASE 2: A 42-year-old physician with episodic supraventricular tachycardia
      had an outpatient ablation procedure. Two weeks later he presented with a swollen
      painful leg, with Doppler showing complete thrombotic occlusion of the common
      femoral, popliteal, and superficial femoral veins. Platelet count was 165,000
      before procedure, 111,000 on representation, and 66,000 after intravenous heparin
      infusion was started. Shortness of breath and documented pulmonary embolus
      ensued. When a heparin antibody test ordered 5 days after admission came back
      very strongly positive, a direct thrombin inhibitor was begun. The patient
      demanded transfer to our hospital. His subsequent course was benign, including
      transition to warfarin and discontinuation of anticoagulants after 6 months.

PMID- 22143470
TI  - Perioperative management of antithrombotic therapy in cardiovascular patients.
AB  - Many patients with underlying cardiovascular disease require long-term
      anticoagulation. The perioperative or periprocedural management of patients who
      require temporary interruption of anticoagulant or antiplatelet medications is a
      common and often challenging clinical problem. It requires a fine balance between
      the risk of thromboembolic events during anticoagulant interruption and the risk
      of bleeding in the setting of antithrombotic therapy administered around the time
      of surgery. Interruption of anticoagulation is associated with an increased risk
      of thromboembolic events. Stratifying patients into thromboembolic risk groups
      may be helpful in directing anticoagulation management in the perioperative
      setting. Bridging anticoagulation, generally with low-molecular-weight heparin
      (LMWH), is often an integral part of perioperative thrombosis risk reduction.
      Perioperative anticoagulation management varies depending on the indication for
      anticoagulation and the anticoagulant or antiplatelet agent being used by the
      patient. In this article, we review some of the general principles involved with
      perioperative anticoagulation and discuss the perioperative management of
      patients taking vitamin K antagonists (VKAs), bridging regimens for
      anticoagulants and antiplatelet agents, and strategies for managing patients on
      the newer oral anticoagulants.

PMID- 22143471
TI  - Enhanced strategies for prevention and management of blood loss in special,
      unusual, and unexpected surgical situations.
AB  - Typically, surgical and anesthesia teams work together in the operating room to
      control blood loss by thoroughly evaluating bleeding risk preoperatively and by
      using their training in the treatment of intraoperative blood loss. As a result,
      most bleeding is usually well controlled. In many cases a hematologist is
      consulted for recommendations preoperatively or, in urgent situations, even while
      the patient is in the operating room. In the end, however, it is usually the
      surgeons and anesthesiologists making decisions about how best to control
      bleeding. What follows is an update on currently available options in the
      management of surgical bleeding (Table 1).

PMID- 22143472
TI  - Balancing hemostasis and thrombosis in interventional vascular medicine and
      surgery.
AB  - Antithrombotic therapy and revascularization are critical factors in managing
      patients presenting with acute coronary syndromes and are described in multiple
      guidelines documents. In addition to preventing intravascular thrombosis, they
      increase the risk of bleeding, which has been implicated as a risk factor in
      short- and long-term mortality. Randomized controlled trials provide useful
      aggregate information comparing the risks and benefits of various therapies. In
      this paper, we will use a case-based format to discuss optimal individualized
      antithrombotic treatments.

PMID- 22143473
TI  - Facts and frictions: conflicts of interest in medical research.
AB  - OVERVIEW: I'm going to give you a bird's eye view, as an editor-in-chief, of why
      conflict of interest in medical research is such a vital problem today in
      medicine. By the time I am finished, I hope that I will convince you that we
      physicians and medical scientists need to make sure we take control of our
      profession to protect our patients in a way that only we can do. The first
      definition of "conflict of interest" that I could find goes back to 1850 in
      Webster's Dictionary: "To conflict between the private interests and the official
      responsibility of a person in a position of trust." That sounds familiar to all
      of us in medicine, because that's who we are. Why do authors and reviewers have
      conflicts of interests? Career advancement, peer recognition, competing research
      interests, competition for research grants, intellectual biases and passions, and
      financial conflicts that we sometimes let get in the way. Editors have conflicts
      of interest because we want to promote our journal and improve our "impact
      factor"--a measure of the average number of citations to articles published in
      scientific journals. The impact factor is often used to gauge the relative
      importance of a journal within its field. I would love to do away with this. It
      is the most manipulative thing in the world because journal editors have to live
      by it, and departments use the impact factor as a mechanism for promotion.
      Editors also want to increase subscriptions and increase the financial
      profitability of their journals; sometimes, they have a conflict of interest
      because they're trying to eliminate or decrease stress, hostility, or harassment.
      In fact, I invite anyone who doesn't think a journal editor deals with stress,
      hostility, or harassment to spend a day with me.

PMID- 22143474
TI  - Updates on critical care management of cardiovascular patients.
AB  - Cardiology and cardiovascular surgery patients have historically been one of the
      sickest populations that physicians encounter. With the inherent compromise of
      the cardiac and/or respiratory system and the added complexity of a major
      surgical procedure, this patient group requires a demanding level of care. As
      innovations in the treatment of cardiac patients have prolonged life, we have
      encountered patients who require redo-redo-redo procedures. There has been a
      tremendous increase in the use of a wide variety of mechanical assist devices,
      transplantation procedures, robotic surgery, and hybrid approaches in which
      cardiac surgeons and cardiologists work in the same room on the same patient.
      Against this background, there have been quite a few changes taking place in the
      field of critical care. This report discusses the transformations being made in
      blood pressure management, blood product transfusion, prevention of
      healthcareassociated infections, physical therapy in cardiothoracic intensive
      care units (ICUs), ventilatory management, and the role of intensivists in
      cardiothoracic ICUs.

PMID- 22143475
TI  - Nephrogenic calcific arteriopathy.
AB  - INTRODUCTION: Vascular calcification in chronic kidney disease (CKD) is extremely
      common and contributes to significant morbidity and mortality among these
      patients. The pathogenesis is complex and involves multiple factors, including
      elevated calcium x phosphorus product as well as deficiencies in circulating or
      locally produced inhibitors of calcification, parathyroid hormone, hyperlipidemia
      and inflammation. Similarly, valvular heart calcifications as well as myocardial
      and pulmonary calcifications of fatal consequences can also occur, presumably
      related to the same pathogenetic factors (Figures 1, 2). Other forms of
      extraskeletal tissue calcification of nonfatal consequences but leading to
      incapacity can also develop in CKD patients (Figure 3). These complications may
      be prevented by awareness and early intervention directed towards correcting some
      of the aforementioned participating mechanisms.

PMID- 22143476
TI  - Detection of adventitial vasa vasorum and intraplaque neovascularization in
      carotid atherosclerotic lesions with contrast-enhanced ultrasound and their role
      in atherosclerosis.
AB  - INTRODUCTION: The development of new surrogate markers of atherosclerosis is a
      crucial goal in the clinical setting, as they may allow physicians to recognize
      unstable lesions early and identify individuals with vulnerable or unstable
      lesions who bear an increased risk of future cardio--and cerebrovascular
      complications. These surrogate markers should be capable of being measured
      noninvasively using safe and reliable methods. Recently, Nambi et al.
      demonstrated how the combined measurement of carotid intima media thickness
      (CIMT) and occurrence of carotid plaques improves the risk prediction of
      cardiovascular outcomes. These results confirm the value of carotid ultrasound
      (US) when combined with traditional Framingham risk factors in assessing a
      patient's risk for atherosclerotic disease. Contrast-enhanced ultrasound (CEUS)
      is a new imaging approach that is evolving and may become a standard clinical
      tool for further atherosclerotic risk stratification in the future. The contrast
      agents used in US imaging are safe, commercially available, and approved for use
      in echocardiography by the FDA. Thus, CEUS is technically feasible with existing
      approved commercial equipment and can be performed at the bedside or in an
      outpatient setting. However, US contrast agents are not yet approved by the FDA
      for visualization and assessment of the carotid artery and its associated
      pathologies. The cost effectiveness of CEUS has been shown in the context of
      gastrointestinal imaging, and CEUS of carotid atherosclerotic lesions is emerging
      as an approach to complement unenhanced US imaging. By providing the direct
      visualization of adventitial vasa vasorum (VV) and intraplaque
      neovascularization, CEUS is capable of depicting two new surrogate markers of
      atherosclerosis - namely, adventitial VV and intraplaque neovascularization.

PMID- 22143477
TI  - Symptomatic carotid artery stenosis is best treated by carotid endarterectomy.
AB  - INTRODUCTION: Ask a dysphasic patient who has received a carotid artery stent if
      he or she would instead have rather had a troponin enzyme leak or minor
      myocardial infarction (MI). Although the answer is clear to most of us, there are
      many interventionalists and clinicians who have inappropriately interpreted
      recent data from the CREST trial to conclude that carotid artery stenting (CAS)
      is equivalent to carotid endarterectomy (CEA).

PMID- 22143478
TI  - Metastatic melanoma to the intracavitary left ventricle treated using cardiac
      autotransplantation technique for resection.
AB  - Melanoma has a known propensity for cardiac metastasis. Most cases are associated
      with widespread metastatic disease and multiple sites of cardiac involvement and
      are not appropriate for surgical resection. When there is an isolated metastasis
      to the heart, the melanoma tends to involve the right heart. Rarely does melanoma
      metastasize only to the left ventricle. We present an unusual case of isolated
      metastasis of melanoma to the intracavitary left ventricle. This tumor was poorly
      responsive to chemotherapy, and a cardiac autotransplantation technique was used
      to achieve complete resection with pathologically negative margins.

PMID- 22143479
TI  - Echocardiography in the diagnosis of pericardial effusion: a historical
      perspective.

PMID- 22143480
TI  - Seven-year clinical performance of CEREC-2 all-ceramic CAD/CAM restorations
      placed within deeply destroyed teeth.
AB  - OBJECTIVES: Adhesively luted all-ceramic restorations represent a promising way
      to preserve and stabilize weakened tooth substance, but little information is
      published about the clinical performance of extensive all-ceramic restorations.
      MATERIALS AND METHODS: A total of 78 large CEREC 2TM single-tooth all-ceramic
      restorations had been placed in 35 patients. After 7 years, 59 teeth in 25
      patients were reevaluated according to USPHS or modified USPHS criteria regarding
      aesthetic properties, e.g., "anatomic form," "color match," and "marginal
      discoloration"; functional properties, e.g., "marginal integrity," wear expressed
      by the criteria "proximal contact" and "static/dynamic occlusal relationship";
      and biological properties, e.g., "tooth vitality" and "secondary caries".
      Additionally, the "proportion of margin below/above cemento-enamel junction" was
      included. RESULTS: Two restorations had failed prior to the 7-year recall, one
      due to a bulk fracture of the restoration and one due to poor marginal integrity
      (rated "Charlie") after 4 years. Other six restorations were rated as failure at
      the 7-year evaluation (three restorations revealed secondary caries, one was bulk
      fracture of the Cerec 2 restoration, and two failures were related to endodontic
      problems resulting in extraction or amputation of one root, respectively),
      resulting in a failure rate of 13.1% after 7 years. A total of 96.4% of the
      restorations revealed sufficient ratings for esthetic properties "anatomic form,"
      "color match," "marginal discoloration," and "marginal integrity". CONCLUSIONS:
      The survival rate of 86.9% at the 7-year recall demonstrates that adhesively
      luted all-ceramic CAD/CAM-generated restorations are suitable for restoration of
      extended coronal defects. CLINICAL RELEVANCE: CAD/CAM-generated all-ceramic
      restorations facilitate the reconstruction of deeply destroyed teeth
      irrespectively of the location of the cavity margins.

PMID- 22143484
TI  - Changing the face of nursing: reducing ethnic and racial disparities in health.
AB  - This article reports on findings from a Nursing Diversity Workforce grant, BEST
      (Becoming Excellent Students in Transition to Nursing), designed to assist
      students from minority and educationally disadvantaged backgrounds to become
      culturally competent registered nurses. A program of retention strategies that
      included peer and faculty tutoring, counseling, and financial support helped to
      remove barriers to success in nursing. All but 3 of the enrolled students either
      have graduated or are on track to doing so. Most graduates are practicing in the
      city where they are helping to reduce health disparities through their
      contributions to improved health care for vulnerable populations.

PMID- 22143481
TI  - Excessive fluoride intake alters the MMP-2, TIMP-1 and TGF-beta levels of
      periodontal soft tissues: an experimental study in rabbits.
AB  - OBJECTIVES: This study evaluated the influence of fluoride on periodontal soft
      tissues by investigating any alterations in their MMP-2, TIMP-1 and TGF-beta
      profiles secondary to excessive fluoride intake. MATERIAL AND METHODS: Fluorosis
      was induced in 18 rabbits (test group) through consumption of fluoride added to
      drinking water, whereas 10 rabbits consumed regular tap water as daily supply
      (control group). Following fluorosis verification, animals were sacrificed and
      their 1st mandibular molar teeth were utilized in the assessments. MMP-2, TIMP-1
      and TGF-beta were separately investigated for gingival epithelium (GE), gingival
      connective tissue (GC) and periodontal ligament (PL) to evaluate periodontal soft
      tissues. Histological sections were prepared from the groups, the parameters were
      determined by immunohistochemistry, and their levels were calculated by
      quantification of the immunostainings. RESULTS: Staining intensity of MMP-2 in GC
      and PL (p < 0.01); TIMP-1 and TGF-beta of GE, GC and PL (p < 0.01) were higher in
      the test group compared to those of the control group. Intra-group staining of
      TIMP-1 was higher than MMP-2 in all test group compartments (p < 0.01) and in the
      control group GE (p < 0.01). TIMP-1 was also higher than TGF-beta in the GE and
      PL of the test group (p < 0.05) and in the GE of the control group (p < 0.01).
      CONCLUSION: These results suggest that excessive fluoride intake may affect
      periodontal soft tissues by increasing MMP-2, TIMP-1 and TGF-beta, and thereby
      altering the MMP-2/TIMP-1 and TIMP-1/TGF-beta ratios. CLINICAL RELEVANCE:
      Excessive fluoride consumption may alter the periodontal tissue homeostasis which
      may be detrimental in the maintenance of periodontal health.

PMID- 22143485
TI  - Increasing information-seeking about human papillomavirus vaccination through
      community partnerships in African American and Hispanic communities.
AB  - This study tested the feasibility of promoting 1-800-4-CANCER through
      partnerships with organizations serving African American and Hispanic
      communities. Small-media and client reminders about human papillomavirus
      vaccination were made available through local agents to 28 community
      organizations. Organizations ordered 79 932 resources and distributed them to
      young women and parents of girls-;African Americans in St Louis, Missouri, and
      Hispanics in the Lower Rio Grande Valley of Texas. Pre- to postintervention calls
      to 1-800-4-CANCER increased 38% in these communities, while declining 15% in
      comparison communities of Kansas City, Missouri, and El Paso, Texas (F = 8.6, P =
      .004) and 1.4% in the United States as a whole.

PMID- 22143486
TI  - Community strategies to address cancer disparities in Appalachian Kentucky.
AB  - Central Appalachian residents suffer disproportionate health disparities,
      including an all-cancer mortality rate 17% higher than the general population.
      During 10 focus groups and 19 key informant interviews, 91 Appalachian residents
      identified cancer screening challenges and strategies. Challenges included (1)
      inadequate awareness of screening need, (2) insufficient access to screening, and
      (3) lack of privacy. Strategies included (1) witnessing/storytelling, (2)
      capitalizing on family history, (3) improving publicity about screening
      resources, (4) relying on lay health advisors, and (5) bundling preventive
      services. These insights shaped our community-based participatory research
      intervention and offered strategies to others working in Appalachia, rural
      locales, and other traditionally underserved communities.

PMID- 22143487
TI  - Engaging the Dan River Region to reduce obesity: application of the Comprehensive
      Participatory Planning and Evaluation process.
AB  - Despite ongoing recommendations to engage health-disparate populations in the
      initiation and execution of community-based research, few studies report on the
      process of community engagement. The action-oriented Comprehensive Participatory
      Planning and Evaluation (CPPE) process is designed to guide community health
      planning and evaluation. This article describes how the CPPE process was utilized
      within a community-based participatory research initiative aimed at addressing
      obesity in the health-disparate Dan River Region. Encouraging community
      engagement in formulating research agendas and promoting ownership of health
      solutions will be key to improving obesity risk factors among Dan River Region
      residents and similar vulnerable communities.

PMID- 22143488
TI  - Adaptation of problem-solving treatment for prevention of depression among low
      income, culturally diverse mothers.
AB  - Adapting evidence-based interventions to be more accessible and culturally
      sensitive to the needs of diverse populations is a potential strategy to address
      disparities in mental health care. We adapted an evidence-based depression
      treatment strategy, Problem-Solving Treatment, to prevent depression among low
      income mothers with vulnerable children. Intervention adaptations spanned 3
      domains: (1) the intervention's new prevention focus, (2) conducting a parent
      focused intervention in venues oriented to children; and (3) cultural competency.
      The feasibility of adaptations was assessed through 2 pilot-randomized trials (n
      = 93), which demonstrated high participant adherence, satisfaction, and
      retention, demonstrating the feasibility of our adaptations.

PMID- 22143489
TI  - Parental influence on obesity in Northern Plains American Indian youth.
AB  - Little is known regarding American Indian (AI) parental influence on children's
      diet and physical activity (PA), or if this influence is associated with
      childhood weight. We compared AI parents' diet, PA, and support for these
      behaviors with the child's body mass index. Scores for parental support of
      positive PA and diet were higher among parents of overweight/obese children.
      Parent PA and nutrition behaviors were in a similar, but not significant,
      direction with respect to child body mass index. Findings suggest that future
      research is needed to determine what parental, societal, or community variables
      influence AI children to engage in healthy eating and PA, especially if they are
      overweight or obese, and the age at which these variables would have the most
      impact on these behaviors.

PMID- 22143490
TI  - A successful guide in understanding Latino immigrant patients: an aid for health
      care professionals.
AB  - The recent growth of Latino immigrants in the United States has presented great
      challenges to the health care system, particularly in "emerging Latino states."
      An educational DVD was developed to aid professionals in providing culturally
      competent care to Latino immigrants and better understand their expectations when
      seeking care, as well as common cultural beliefs and practices. Knowledge and
      confidence was assessed through pre- and posttest measurements among 515 health
      care professionals nationwide. Results indicated significant increase (P < .001)
      in overall knowledge/confidence in Latino cultural beliefs as they relate to
      health care seeking, differences in health care systems between the United States
      and Latin America, and barriers to health care. Such multimedia training may be a
      promising approach to improving health care with Latino immigrants in the United
      States.

PMID- 22143491
TI  - Short-term in vivo precision of BMD and parameters of trabecular architecture at
      the distal forearm and tibia.
AB  - In vivo hr-pQCT precision was determined in 42 postmenopausal women using double
      baseline measurements from a multicenter trial of odanacatib. Errors, e.g., at
      the radius below 1.3% for BMD and below 6.3% for trabecular structure, were
      comparable to single-center results. Motion artifacts remain a challenge,
      particularly at the forearm. INTRODUCTION: The short-term in vivo precision of
      BMD, trabecular bone structure, cortical thickness and porosity of the forearm
      and tibia was measured by hr-pQCT. Also the effect of image quality on precision
      was evaluated. METHODS: In 42 postmenopausal women (age 64.4 +/- 6.8 years) out
      of 214 subjects enrolled in a multi center advanced imaging phase III study of
      odanacatib (DXA spine or hip T-scores between -1.5 and -3.5), double baseline hr
      pQCT (XtremeCT) measurements with repositioning were performed. The standard
      ultradistal location and a second, more proximally located VOI were measured at
      the radius and tibia to better assess cortical thickness and porosity. Image
      analysis and quality grading (grades: perfect, slight artifacts, pronounced
      artifacts, unacceptable) were performed centrally. RESULTS: At the radius RMS%CV
      values varied from 0.7% to 1.3% for BMD and BV/TV and from 5.6% to 6.3% for
      Tb.Sp, Tb.Th, Tb.N, and cortical porosity. Numerically at the tibia, precision
      errors were approx. 0.5% lower for BMD and 1% to 2% lower for structural
      parameters although most differences were insignificant. In the radius but not in
      the tibia, precision errors for cortical thickness were smaller at the distal
      compared to the ultradistal location (1% versus 2%). CONCLUSIONS: BMD precision
      errors were lower than those for trabecular architecture and cortical porosity.
      Motion artifacts remain a challenge, particularly at the forearm. Quality grading
      remains subjective, and more objective evaluation methods are needed. Precision
      in the context of a multicenter clinical trial, with centralized training and
      scan analysis, was comparable to single-center results previously reported.

PMID- 22143492
TI  - The c-Abl expression in uterine epithelium during the mouse estrus cycle.
AB  - The epithelial cells of the mouse endometrium comprises the recurring physiologic
      changes such as proliferation and apoptosis induced by the reproductive hormones
      throughout the estrus cycle. The c-Abl is a protein tyrosine kinase, localized in
      the different cellular compartments such as nucleus, cytoplasm, mitochondria, and
      endoplasmic reticulum, interacts with different cellular proteins, including
      signaling adaptors, kinases, phosphatases, cell-cycle regulators, transcription
      factors and cytoskeletal proteins. Our hypothesis is that the c-Abl expression in
      the mouse uterine epithelium shows cyclic changes during the estrus cycle that is
      involved in regulation of the endometrial epithelial cells. The regulation of c
      Abl gene and protein expression in the uterus of intact animals in the different
      cycle phases was investigated using immunohistochemistry, western blot and semi
      quantitative RT-PCR. The immunohistochemistry results revealed that the luminal
      and the glandular epithelium (LE) and (GE), respectively, showed gradually
      increase in the expression of c-Abl from the proestrus (P) to the metestrus and
      followed by a decrease in the diestrus (D). c-Abl immunoreactivity was detected
      in the both LE and GE cells, especially the LE showed diminished the c-Abl
      protein expression on the D phase and the minimal value was detected on the P
      day. The c-Abl protein level in the LE was increased during the M, presenting a
      high correlation with the hormonal level of this cell type. The result of c-Abl
      RT-PCR analysis was compatible with pattern of c-Abl protein expression. In
      conclusion, the stage-specific protein pattern of the mammalian c-Abl tyrosine
      kinase presented a good correlation with the mouse estrus cycle and may have a
      regulative function during the uterine remodeling.

PMID- 22143493
TI  - Ndrg2 expression in neurogenic germinal zones of embryonic and postnatal mouse
      brain.
AB  - N-myc downstream-regulated gene 2 (Ndrg2) is well-known for its involvement in
      tumor cell proliferation and differentiation. This promotes us to investigate
      whether Ndrg2 also functions in neurogenesis, during which some cellular events
      are similar to that of tumorigenesis. As the first step in exploring the role of
      Ndrg2 in neurogenesis, here we performed in situ hybridization with a Ndrg2
      specific probe to examine Ndrg2 mRNA expression in neurogenic germinal zones of
      embryonic and postnatal mouse brain. Our results showed that Ndrg2 mRNA was
      highly expressed in the cortical ventricular zone at various embryonic stages. At
      postnatal stages, Ndrg2 transcripts were downregulated but still abundant in the
      subventricular zone of lateral ventricle and subgranular zone of hippocampal
      dentate gyrus where persistent neurogenesis occurs in the mammalian brain
      throughout life. Double staining of Ndrg2 mRNA with proliferation markers BrdU
      and Ki67, or with neural progenitor cell marker Nestin revealed that Ndrg2 was
      expressed in proliferating precursor cells. Thus, abundant expression of Ndrg2
      mRNA in neural proliferating cell populations indicates an important role of
      Ndrg2 in neurogenesis of both embryonic and postnatal mouse brain.

PMID- 22143494
TI  - The effect of Rho kinase inhibitor Y-27632 on endotoxemia-induced intestinal
      apoptosis in infant rats.
AB  - The aim of this study was to evaluate the effect of Rho kinase inhibitor, Y-27632
      on the intestinal apoptosis in endotoxemic infant rats. Wistar albino 15-17-day
      old rat pups (n = 21) were randomized to three experimental groups: (1) controls;
      (2) endotoxemia (LPS); and (3) endotoxemia treated with Y-27632 (LPS + Y-27632).
      Endotoxemia was induced in rats by intraperitoneal (i.p) injection of
      lipopolysaccharide (Escherichia coli serotype 0111:B4; 10 mg/kg). Y-27632 was
      administered 5 mg/kg i.p at three times, just, 8 and 16 h after LPS injection.
      Twenty-four hours after LPS injection, intestinal apoptosis was assessed by
      hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling assay and immunohistochemistry for active caspase-3.
      Endotoxemia induced extensive apoptotic injury in the intestinal tissues. The
      administration of Y-27632 to endotoxemic infant rats caused a marked decrease in
      the number of apoptotic cells in both intestinal epithelium and lamina propria.
      In conclusion, the inhibition of Rho kinase with Y-27632 diminished the
      intestinal apoptotic damage induced by endotoxemia in infant rats.

PMID- 22143495
TI  - The effect of monosodium glutamate on the cerebellar cortex of male albino rats
      and the protective role of vitamin C (histological and immunohistochemical
      study).
AB  - Monosodium glutamate (MSG) is a natural constituent of many foods and was
      reported to have neurotoxic effects. The aim of this study was to investigate the
      possible toxic effect of MSG on histological and glial fibrillary acidic protein
      (GFAP) immunohistochemical features of cerebellar cortex of albino rats and to
      evaluate the possible protective role of vitamin C against this effect. Thirty
      rats were divided into 3 equal groups. Group I, control; Group II, treated with 3
      g/kg/day of MSG and Group III, received 100 mg/kg/day of vitamin C simultaneously
      with MSG. After 14 days, cerebellar tissues were obtained and processed to
      prepare sections stained with H&E, toluidine blue. The GFAP was detected
      immunohistochemically. Histological examination of group II showed degenerative
      changes as pyknotic Purkinje and granule cells with areas of degeneration
      surrounded by inflammatory cells in granular layer. However, group III showed
      more preserved histological structure of cerebellar cortex. Statistical analysis
      of area percent of the GFAP immunoreaction among studied groups showed
      significant increase in group III when compared with group I and group II.
      However, a non significant increase was detected in group II when compared with
      group I. In conclusion, MSG has neurotoxic effect leading to degenerative changes
      in neurons and astrocytes in cerebellar cortex of albino rats and vitamin C
      supplementation could protect from these changes. Getting more attention to the
      constituents of food products is recommended and vitamin C could be advised to
      protect people from food oxidants additives.

PMID- 22143496
TI  - Oxidative stress: a new risk factor for thyroid cancer.
AB  - Oxidative stress (OS) is a state of excessive free radicals and reactive
      metabolites among which the most important class is reactive oxygen species (ROS)
      - radicals derived from oxygen - as represented by the superoxide anion radical
      (O2(.-)) and its reactive metabolites, hydroxyl radical (.OH) and hydrogen
      peroxide (H(2)O(2)). In essence, OS represents an imbalance between the
      production of oxidants - ROS - and their elimination by antioxidative systems in
      the body. Many studies have linked OS to thyroid cancer by showing its
      association with abnormally regulated oxidative or antioxidative molecules. The
      study by Wang et al. in the December 2011 issue of Endocrine-Related Cancer (18,
      773-782) further supports this relationship by demonstrating a high total oxidant
      status and OS index in thyroid cancer patients. The origin of ROS in thyroid
      cancer patients has not been defined, but thyroid cancer itself can be one since
      inflammation, a major event in it, is a classical source of ROS. ROS may in turn
      enhance the mitogen-activated protein (MAP) kinase and phosphatidylinositol-3
      kinase (PI3K) pathways, forming a vicious cycle propelling thyroid tumorigenesis.
      Regardless of the mechanism, the clinical implication of the association of OS
      with thyroid cancer is severalfold: one, OS is a new risk factor for thyroid
      cancer; two, OS confers thyroid cancer patients an increased risk for
      cardiovascular diseases, degenerative neurological disorders, and other cancers
      that are classically associated with OS; and three, interference with OS may
      reduce this risk and be therapeutically beneficial to thyroid cancer itself in
      thyroid cancer patients. These interesting possibilities deserve further studies.

PMID- 22143499
TI  - In these pages.... The 7th International Sandor Ferenczi Conference.

PMID- 22143498
TI  - Promoter hypermethylation patterns in fallopian tube epithelium of BRCA1 and
      BRCA2 germ line mutation carriers.
AB  - BRCA1/2 germ line mutation carriers have a high risk of developing fallopian tube
      carcinoma (FTC), thought to occur through different early (p53 signatures) and
      later (dysplasia, intra-epithelial carcinoma) premalignant stages. Promoter
      hypermethylation of tumour suppressor genes is known to play a key role in
      (early) carcinogenesis. However, little is known about methylation in normal and
      (pre)malignant fallopian tube tissue. We identified 14 areas of p53 accumulation
      in the fallopian tubes of BRCA mutation carriers. Cells from these areas were
      harvested together with cells from adjacent benign appearing areas. An age
      matched non-BRCA sporadic control group (n=13) and eight sporadic FTCs were
      included as negative and positive controls respectively. Methylation-specific
      multiplex ligation-dependent probe amplification was used to assess promoter
      methylation of 70 tumour suppressor genes in all samples. We observed a gradual
      increase in methylation from sporadic control tissue (median cumulative
      methylation index (CMI) 568.19) through normal tissue and from areas of p53
      accumulation in BRCA carriers (median CMI 687.54 and 676.72) to FTC (median CMI
      780.97). Furthermore, the methylation percentage of many individual tumour
      suppressor genes differed significantly between these groups, gradually
      increasing as for CMI. Between areas with and without p53 accumulation in BRCA
      mutation carriers no significant differences were found. In this paper, we have
      shown that BRCA mutation carriers display increased methylation of tumour
      suppressor genes in their non-malignant fallopian tube epithelium, closer to
      methylation levels in FTC than to normal sporadic tissue. Methylation could,
      therefore, play an important role in the increased risk of gynaecological
      malignancies in BRCA mutation carriers.

PMID- 22143497
TI  - Calorie restriction and rapamycin inhibit MMTV-Wnt-1 mammary tumor growth in a
      mouse model of postmenopausal obesity.
AB  - Obesity is an established risk and progression factor for postmenopausal breast
      cancer. Interventions to decrease caloric intake and/or increase energy
      expenditure beneficially impact tumor progression in normoweight humans and
      animal models. However, despite the increasingly high global prevalence of
      obesity, the effects and underlying mechanisms of these energy balance modulating
      interventions are poorly characterized in obese individuals. The goal of this
      study was to better characterize the mechanism(s) responsible for the link
      between energy balance and breast cancer progression in the postmenopausal
      obesity context. We compared the effects of calorie restriction (CR), treadmill
      exercise (EX), and mammalian target of rapamycin (mTOR inhibitor) treatment on
      body composition, serum biomarkers, cellular signaling, and mammary tumor growth
      in obese mice. Ovariectomized C57BL/6 mice were administered a diet-induced
      obesity regimen for 8 weeks, then randomized into three treatment groups: control
      (semipurified diet fed ad libitum, maintained the obese state); 30% CR
      (isonutrient relative to control except 30% reduction in carbohydrate calories);
      and EX (control diet fed ad libitum plus treadmill exercise). Mice were implanted
      with syngeneic MMTV-Wnt-1 mammary tumor cells at week 12. Rapamycin treatment (5 
      mg/kg every 48  h) started at week 14. Tumors were excised at week 18. CR and
      rapamycin (but not EX) significantly reduced final tumor weight compared to
      control. In follow-up analysis, constitutive activation of mTOR ablated the
      inhibitory effects of CR on Wnt-1 mammary tumor growth. We conclude that mTOR
      inhibition may be a pharmacologic strategy to mimic the anticancer effects of CR
      and break the obesity-breast cancer progression link.

PMID- 22143500
TI  - Transference and countertransference in Sandor Ferenczi's Clinical Diary.
AB  - This paper examines Ferenczi's contributions to the concepts of transference and
      countertransference, especially in the Clinical Diary, and the weight of these
      ideas in our present-day clinical work. Specifically emphasized are the
      circulation of archaic communication within the session, and the denial of
      countertransference as a re-traumatazing agent, shown in a clinical vignette.

PMID- 22143501
TI  - From introjection to intropression: evolution of a theoretical concept and its
      consequences for psychoanalytic technique.
AB  - Here we try to offer a panoramic view on the evolution of the concept of
      introjection in Ferenczi's thinking, until its culmination in the last annotation
      of Notes and Fragments on December 26, 1932. In this final note, Ferenczi
      invented the neologism intropression in which he tried to articulate the notion
      of introjections with the devastating effects of violence and parental
      repression, and a definite way to conceive the analytical practice.

PMID- 22143502
TI  - Things in words: Ferenczi and language.
AB  - Ferenczi defends the mimesis between words and things from the moment he enters
      the psychoanalytical movement. He emphasizes the sensitive dimension of language
      and the magical experience of words. This paper intends to view such use of
      language by contemporary patients in a non-pathologizing, constructive way,
      avoiding characterizing them as deficient in their capacity to symbolize and
      create metaphors.

PMID- 22143503
TI  - Medicating patients in psychoanalytic therapy: implications for introjection,
      transference, and countertransference.
AB  - If a patient comes for psychotherapy or psychoanalysis, why medicate him with
      psychotropic drugs? The answers to this question are explored and addressed from
      several points of view. The central hypothesis of this paper suggests that most
      of the reasons for medicating patients have to do with therapist's unresolved
      countertransference issues. Furthermore, medicating a patient may have
      deleterious effects on his introjected sense of self, and impacts the
      transference relationship in a significant way. The issues surrounding medication
      as adjunctive therapy are elucidated and clarified in terms of rationale,
      efficacy, and the impact on the psychotherapeutic relationship. Psychoanalytic
      solutions are offered and discussed.

PMID- 22143504
TI  - Losing the certainty of self.
AB  - In his theory of trauma, Ferenczi points to the disbelief of adults of a child's
      account of an event as an actual traumatizing factor. Ferenczi also states that
      of all the consequences of the trauma, which include identification with the
      aggressor, psychic coma, departure from the possibility of dreams, and a fall to
      the hell of nightmares, the most important and fundamental is the lack of
      certainty of self. The disbelief of the adults destroys the certainty of what is
      perceived and experienced; it has the power of annihilating the child's belief in
      his own perceptions, his trust in his own senses. The loss of certainty of self
      appears to be a common characteristic in patients with distinct psychic dynamics.
      We will analyze the loss of certainty of self in cases of patients of the NEPECC
      (Nucleo de Estudos em Psicanalise e Clinica da Contemporaneidade) [Center of
      Studies in Psychoanalysis and Contemporarity Clinic] at the Federal University of
      Rio de Janeiro.

PMID- 22143505
TI  - Mad Men: greed, sex, power and presentation--what's changed?

PMID- 22143506
TI  - Narcissism, mania and analysts' envy.
AB  - Character traits like narcissism, mania and grandiosity are routinely discussed
      in the psychoanalytic literature as aspects of psychopathology only. However,
      many individuals who have both achieved and contributed to society in the most
      profound ways often have such characteristics. Psychoanalysts, sometimes envious
      of patients who possess considerable wealth and/or power, may be inclined to
      overly pathologize such qualities, denying their own desires for the perks of
      power and material success. Mad Men is discussed largely in this context.

PMID- 22143507
TI  - The world of Mad Men: power, surface and passion.
AB  - Mad Men is disturbing to post-millennium viewers, particularly those of a
      "certain" age, on three counts. First, it invokes a particular historical context
      of gender oppression; second it captures the prevailing post-War injunction that
      emotional distress is unseemly and distasteful; and third, it captures the
      zeitgeist's celebration of surface over substance in relationship. However, just
      as disturbing as these historically situated interpersonal premises is the
      niggling question that each relationship pairing and each episode leaves with the
      viewer. To wit: How much of the disconnection and the unrequited longings are
      reflective of a particular historical era, and to what degree do they reflect
      timeless aspects of character and relationship? Thus Mad Men provides an
      exquisitely rendered sociocultural tableau in which the viewer struggles, however
      articulated or not, with one of the essential knots of psychoanalytic as well as
      couples treatment: the complicated interpenetration of culture and character, of
      time and timelessness.

PMID- 22143508
TI  - Bodyguard of lies: the vicissitudes of deception among mad men and women.
AB  - The television series Mad Men is critically acclaimed despite grievous flaws as a
      drama. Its immense popularity is important psychological data and needs to be
      explored from the vantage of the dynamics of deception, including motivation,
      appeal and consequences for relationships and the self. The show's creator is
      inspired by John Cheever, the depth of whose complex characterizations is
      contrasted to the lures of the show. The parallel between the manipulations of
      authenticity inherent in advertising, the relationships between those who are
      involved in it and the relationship the show establishes with its audience is
      studied through two contiguous brief scenes that portray multiple reverberating
      deceits. These characters in these scenes are understood as creating both longing
      and disappointment at multiple levels. The psychic costs for both the deceivers,
      those deceived, as well as witnesses to the deception are fundamental.

PMID- 22143510
TI  - As generations speak.

PMID- 22143509
TI  - Gender, splitting and non-recognition in Mad Men.
AB  - The world of Mad Men is one in which life lived on the surface and repression
      dominates the scene. A superficial reading seems to suggest that the classically
      gendered subject-object split characterizes Mad Men: women in the series appear
      devoid of desire, while men possess power, sexuality and agency. But despite its
      blatant sexism, Mad Men's rendering has turned traditional 1960s American culture
      on its head. There is no subject-object split in Mad Men because men do not have
      access to the subject position; they, as much as women, remain objects to
      themselves and their partners. In the absence of mutual recognition, serotics
      ultimately fails.

PMID- 22143511
TI  - Inside the revolution: power, sex, and technique in Freud's " 'wild' analysis".

PMID- 22143512
TI  - Trans: gender in free fall.

PMID- 22143513
TI  - Play's magic and play's limits.

PMID- 22143516
TI  - Neurodegeneration as a consequence of failed mitochondrial maintenance.
AB  - Maintaining the functional integrity of mitochondria is pivotal for cellular
      survival. It appears that neuronal homeostasis depends on high-fidelity
      mitochondria, in particular. Consequently, mitochondrial dysfunction is a
      fundamental problem associated with a significant number of neurological
      diseases, including Parkinson's disease (PD), Huntington's disease (HD),
      Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and various
      peripheral neuropathies, as well as the normal aging process. To ensure optimal
      mitochondrial function, diverse, evolutionarily conserved mitochondrial quality
      control mechanisms are in place, including the scavenging of toxic reactive
      oxygen species (ROS) and degradation of damaged mitochondrial proteins, but also
      turnover of whole organelles. In this review we will discuss various mitochondria
      associated conditions, focusing on the role of protein turnover in mitochondrial
      maintenance with special emphasis on neurodegenerative disorders.

PMID- 22143517
TI  - Importance of confirming data on the in vivo efficacy of novel antibacterial drug
      regimens against various strains of Mycobacterium tuberculosis.
AB  - In preclinical testing of antituberculosis drugs, laboratory-adapted strains of
      Mycobacterium tuberculosis are usually used both for in vitro and in vivo
      studies. However, it is unknown whether the heterogeneity of M. tuberculosis
      stocks used by various laboratories can result in different outcomes in tests of
      antituberculosis drug regimens in animal infection models. In head-to-head
      studies, we investigated whether bactericidal efficacy results in BALB/c mice
      infected by inhalation with the laboratory-adapted strains H37Rv and Erdman
      differ from each other and from those obtained with clinical tuberculosis
      strains. Treatment of mice consisted of dual and triple drug combinations of
      isoniazid (H), rifampin (R), and pyrazinamide (Z). The results showed that not
      all strains gave the same in vivo efficacy results for the drug combinations
      tested. Moreover, the ranking of HRZ and RZ efficacy results was not the same for
      the two H37Rv strains evaluated. The magnitude of this strain difference also
      varied between experiments, emphasizing the risk of drawing firm conclusions for
      human trials based on single animal studies. The results also confirmed that the
      antagonism seen within the standard HRZ regimen by some investigators appears to
      be an M. tuberculosis strain-specific phenomenon. In conclusion, the specific
      identity of M. tuberculosis strain used was found to be an important variable
      that can change the apparent outcome of in vivo efficacy studies in mice. We
      highly recommend confirmation of efficacy results in late preclinical testing
      against a different M. tuberculosis strain than the one used in the initial mouse
      efficacy study, thereby increasing confidence to advance potent drug regimens to
      clinical trials.

PMID- 22143518
TI  - Chemotherapy-associated changes of histopathological features of Mycobacterium
      ulcerans lesions in a Buruli ulcer mouse model.
AB  - Combination chemotherapy with rifampin and streptomycin (RIF-STR) for 8 weeks is
      currently recommended by the WHO as the first-line treatment for Mycobacterium
      ulcerans infection (Buruli ulcer). To gain better insight into the mode of action
      of these antibiotics against established M. ulcerans infection foci and to
      characterize recovery of local immune responses during chemotherapy, we conducted
      a detailed histopathological study of M. ulcerans-infected and RIF-STR-treated
      mice. Mice were inoculated with M. ulcerans in the footpad and 11 weeks later
      treated with RIF-STR. Development of lesions during the first 11 weeks after
      infection and subsequent differences in disease progression between RIF-STR
      treated and untreated mice were studied. Changes in histopathological features,
      footpad swelling, and number of CFU were analyzed. After inoculation with M.
      ulcerans, massive infiltrates dominated by polymorphonuclear leukocytes developed
      at the inoculation site but did not prevent bacterial multiplication. Huge
      clusters of extracellular bacteria located in large necrotic areas and surrounded
      by dead leukocytes developed in the untreated mice. Chemotherapy with RIF-STR led
      to a rapid drop in CFU associated with loss of solid Ziehl-Neelsen staining of
      acid-fast bacilli. Development of B-lymphocyte clusters and of macrophage
      accumulations surrounding the mycobacteria demonstrated the resolution of local
      immune suppression. Results demonstrate that the experimental M. ulcerans mouse
      infection model will be a valuable tool to investigate efficacy of new treatment
      regimens and of candidate vaccines.

PMID- 22143519
TI  - Mechanisms of resistance to chloramphenicol in Pseudomonas putida KT2440.
AB  - Pseudomonas putida KT2440 is a chloramphenicol-resistant bacterium that is able
      to grow in the presence of this antibiotic at a concentration of up to 25 MUg/ml.
      Transcriptomic analyses revealed that the expression profile of 102 genes changed
      in response to this concentration of chloramphenicol in the culture medium. The
      genes that showed altered expression include those involved in general
      metabolism, cellular stress response, gene regulation, efflux pump transporters,
      and protein biosynthesis. Analysis of a genome-wide collection of mutants showed
      that survival of a knockout mutant in the TtgABC resistance-nodulation-division
      (RND) efflux pump and mutants in the biosynthesis of pyrroloquinoline (PQQ) were
      compromised in the presence of chloramphenicol. The analysis also revealed that
      an ABC extrusion system (PP2669/PP2668/PP2667) and the AgmR regulator (PP2665)
      were needed for full resistance toward chloramphenicol. Transcriptional arrays
      revealed that AgmR controls the expression of the pqq genes and the operon
      encoding the ABC extrusion pump from the promoter upstream of open reading frame
      (ORF) PP2669.

PMID- 22143520
TI  - Biochemical study of the comparative inhibition of hepatitis C virus RNA
      polymerase by VX-222 and filibuvir.
AB  - Filibuvir and VX-222 are nonnucleoside inhibitors (NNIs) that bind to the thumb
      II allosteric pocket of the hepatitis C virus (HCV) RNA-dependent RNA polymerase.
      Both compounds have shown significant promise in clinical trials and, therefore,
      it is relevant to better understand their mechanisms of inhibition. In our study,
      filibuvir and VX-222 inhibited the 1b/Con1 HCV subgenomic replicon, with 50%
      effective concentrations (EC(50)s) of 70 nM and 5 nM, respectively. Using several
      RNA templates in biochemical assays, we found that both compounds preferentially
      inhibited primer-dependent RNA synthesis but had either no or only modest effects
      on de novo-initiated RNA synthesis. Filibuvir and VX-222 bind to the HCV
      polymerase with dissociation constants of 29 and 17 nM, respectively. Three
      potential resistance mutations in the thumb II pocket were analyzed for effects
      on inhibition by the two compounds. The M423T substitution in the RNA polymerase
      was at least 100-fold more resistant to filibuvir in the subgenomic replicon and
      in the enzymatic assays. This resistance was the result of a 250-fold loss in the
      binding affinity (K(d)) of the mutated enzyme to filibuvir. In contrast, the
      inhibitory activity of VX-222 was only modestly affected by the M423T
      substitution but more significantly affected by an I482L substitution.

PMID- 22143522
TI  - Immobilization of antibacterial dihydropyrrol-2-ones on functional polymer
      supports to prevent bacterial infections in vivo.
AB  - Antibiotic-resistant Staphylococcus aureus is of great concern, as it causes a
      wide range of life-threatening infections. The current study demonstrates that
      dihydropyrrolone (DHP)-coated polyacrylamide substrates are effective in reducing
      the number of culturable clinical isolates of S. aureus in vitro in a dose
      dependent manner and are able to reduce the pathogenic potential of
      staphylococcal infection in a subcutaneous infection model. Covalently bound DHPs
      therefore show great potential for use as an antimicrobial strategy in device
      related applications.

PMID- 22143521
TI  - Aerosolized gentamicin reduces the burden of tuberculosis in a murine model.
AB  - Tuberculosis (TB) is a major infectious disease problem: 1.7 million people
      annually die due to TB. Emergence of drug-resistant Mycobacterium tuberculosis
      and the lack of new antibiotics have exacerbated the situation. There is an
      urgent need to develop or repurpose drugs against TB. We evaluated inhaled
      gentamicin as direct respiratory system-targeted therapy in a murine model of TB.
      Aerosolized-gentamicin-treated mice showed significantly reduced lung M.
      tuberculosis loads and fewer granulomas relative to untreated controls. These
      results suggest that direct delivery of antibiotics to the respiratory system may
      provide therapeutic benefit to conventional treatment regimes for treatment of
      pulmonary TB.

PMID- 22143523
TI  - Identification of new antileishmanial leads from hits obtained by high-throughput
      screening.
AB  - A previous screen of ~200,000 compounds from the PubChem database identified 70
      compounds possessing 50% effective concentrations (EC(50)s) below 1 MUM against
      Leishmania major promastigotes that were not toxic to mammalian epithelial cancer
      cells at this concentration (E. Sharlow et al., PLoS Negl. Trop. Dis. 3:e540,
      2009). Based on availability and chemical exclusion criteria, 31 of these
      compounds were purchased from commercial suppliers and evaluated for in vitro
      activity against intracellular L. donovani and L. amazonensis parasites.
      Benzothiazole cyanine compounds (PubChem 16196319 and 16196223) displayed potent
      activity against intracellular amastigotes, prompting a search for commercially
      available compounds that were structurally related. Pubchem 123859 (the cyanine
      dye thiazole orange) showed exceptionally potent activity against intracellular
      L. donovani in vitro (50% inhibitory concentration [IC(50)] = 21 +/- 12 nM) and
      low cytotoxicity against Vero cells (IC(50) = 7,800 +/- 200 nM). Administration
      of 123859 and 16196319 at a dose of 1 mg/kg of body weight intraperitoneally
      (i.p.) daily for 5 days resulted in 44% +/- 4% and 42% +/- 3% suppression of
      liver parasitemia in L. donovani-infected BALB/c mice, respectively, compared to
      the untreated control group (the reductions in liver parasitemia were 30% +/- 5%
      and 27% +/- 4%, respectively, compared to the (2-hydroxypropyl)-beta-cyclodextrin
      solution (HPbetaCD) vehicle control, which itself displayed some antileishmanial
      activity). Benzothiazole-containing cyanine dyes are thus potential lead
      compounds for the discovery of novel antileishmanial agents.

PMID- 22143524
TI  - Pharmacological and patient-specific response determinants in patients with
      hospital-acquired pneumonia treated with tigecycline.
AB  - Pharmacokinetic and clinical data from tigecycline-treated patients with hospital
      acquired pneumonia (HAP) who were enrolled in a phase 3 clinical trial were
      integrated in order to evaluate pharmacokinetic-pharmacodynamic (PK-PD)
      relationships for efficacy. Univariable and multivariable analyses were conducted
      to identify factors associated with clinical and microbiological responses, based
      on data from 61 evaluable HAP patients who received tigecycline intravenously as
      a 100-mg loading dose followed by 50 mg every 12 h for a minimum of 7 days and
      for whom there were adequate clinical, pharmacokinetic, and response data. The
      final multivariable logistic regression model for clinical response contained
      albumin and the ratio of the free-drug area under the concentration-time curve
      from 0 to 24 h (fAUC(0-24)) to the MIC (fAUC(0-24):MIC ratio). The odds of
      clinical success were 13.0 times higher for every 1-g/dl increase in albumin (P <
      0.001) and 8.42 times higher for patients with fAUC(0-24):MIC ratios of >=0.9
      compared to patients with fAUC(0-24):MIC ratios of <0.9 (P = 0.008). Average
      model-estimated probabilities of clinical success for the albumin/fAUC(0-24):MIC
      ratio combinations of <2.6/<0.9, <2.6/>=0.9, >=2.6/<0.9, and >=2.6/>=0.9 were
      0.21, 0.57, 0.64, and 0.93, respectively. For microbiological response, the final
      model contained albumin and ventilator-associated pneumonia (VAP) status. The
      odds of microbiological success were 21.0 times higher for every 1-g/dl increase
      in albumin (P < 0.001) and 8.59 times higher for patients without VAP compared to
      those with VAP (P = 0.003). Among the remaining variables evaluated, the MIC had
      the greatest statistical significance, an observation which was not surprising
      given the differences in MIC distributions between VAP and non-VAP patients
      (MIC(50)and MIC(90) values of 0.5 and 0.25 mg/liter versus 16 and 1 mg/liter for
      VAP versus non-VAP patients, respectively; P = 0.006). These findings
      demonstrated the impact of pharmacological and patient-specific factors on the
      clinical and microbiological responses.

PMID- 22143525
TI  - Resistance to linezolid caused by modifications at its binding site on the
      ribosome.
AB  - Linezolid is an oxazolidinone antibiotic in clinical use for the treatment of
      serious infections of resistant Gram-positive bacteria. It inhibits protein
      synthesis by binding to the peptidyl transferase center on the ribosome. Almost
      all known resistance mechanisms involve small alterations to the linezolid
      binding site, so this review will therefore focus on the various changes that can
      adversely affect drug binding and confer resistance. High-resolution structures
      of linezolid bound to the 50S ribosomal subunit show that it binds in a deep
      cleft that is surrounded by 23S rRNA nucleotides. Mutation of 23S rRNA has for
      some time been established as a linezolid resistance mechanism. Although
      ribosomal proteins L3 and L4 are located further away from the bound drug,
      mutations in specific regions of these proteins are increasingly being associated
      with linezolid resistance. However, very little evidence has been presented to
      confirm this. Furthermore, recent findings on the Cfr methyltransferase
      underscore the modification of 23S rRNA as a highly effective and transferable
      form of linezolid resistance. On a positive note, detailed knowledge of the
      linezolid binding site has facilitated the design of a new generation of
      oxazolidinones that show improved properties against the known resistance
      mechanisms.

PMID- 22143526
TI  - Tn125-related acquisition of blaNDM-like genes in Acinetobacter baumannii.
AB  - A multidrug-resistant Acinetobacter baumannii isolate recovered from a patient
      hospitalized in Switzerland after a transfer from Serbia produced the NDM-1
      carbapenemase. The bla(NDM-1) gene was part of a chromosomally located Tn125
      composite transposon bracketed by two copies of the same insertion sequence,
      ISAba125. This transposon was also associated with the acquisition and expression
      of the bla(NDM-2) gene in an A. baumannii isolate in Germany. Tn125 appears to be
      the main vehicle for dissemination of bla(NDM) genes in that species.

PMID- 22143527
TI  - Quality control strain Campylobacter jejuni ATCC 33560 contains a frameshift
      mutation in the CmeR regulator.

PMID- 22143528
TI  - A physiologically based pharmacokinetic model for capreomycin.
AB  - The emergence of multidrug-resistant tuberculosis (MDR-TB) has led to a renewed
      interest in the use of second-line antibiotic agents. Unfortunately, there are
      currently dearths of information, data, and computational models that can be used
      to help design rational regimens for administration of these drugs. To help fill
      this knowledge gap, an exploratory physiologically based pharmacokinetic (PBPK)
      model, supported by targeted experimental data, was developed to predict the
      absorption, distribution, metabolism, and excretion (ADME) of the second-line
      agent capreomycin, a cyclic peptide antibiotic often grouped with the
      aminoglycoside antibiotics. To account for interindividual variability, Bayesian
      inference and Monte Carlo methods were used for model calibration, validation,
      and testing. Along with the predictive PBPK model, the first for an
      antituberculosis agent, this study provides estimates of various key
      pharmacokinetic parameter distributions and supports a hypothesized mechanism for
      capreomycin transport into the kidney.

PMID- 22143529
TI  - High rates of perinatal group B Streptococcus clindamycin and erythromycin
      resistance in an upstate New York hospital.
AB  - The objective of this study was to evaluate the rates of clindamycin and
      erythromycin resistance among group B Streptococcus (GBS)-positive isolates
      cultured from pregnant women in an upstate New York community hospital. All GBS
      positive perinatal rectovaginal cultures obtained from January 2010 through
      October 2011 were tested for resistance to erythromycin and clindamycin. Among
      the 688 GBS-positive cultures, clindamycin resistance was found in 38.4% and
      erythromycin resistance was found in 50.7%. Rates of GBS resistance to
      clindamycin and erythromycin are much higher than reported in earlier U.S.
      studies, suggesting both increasing resistance and regional variation in
      resistance. These findings lend strong support to the CDC and American College of
      Obstetricians and Gynecologists (ACOG) recommendations that clindamycin use for
      intrapartum antibiotic prophylaxis be restricted to penicillin-allergic women at
      high risk of anaphylaxis and that GBS isolates be tested for antibiotic
      resistance prior to the use of clindamycin in these women.

PMID- 22143530
TI  - E1210, a new broad-spectrum antifungal, suppresses Candida albicans hyphal growth
      through inhibition of glycosylphosphatidylinositol biosynthesis.
AB  - Continued research toward the development of new antifungals that act via
      inhibition of glycosylphosphatidylinositol (GPI) biosynthesis led to the design
      of E1210. In this study, we assessed the selectivity of the inhibitory activity
      of E1210 against Candida albicans GWT1 (Orf19.6884) protein, Aspergillus
      fumigatus GWT1 (AFUA_1G14870) protein, and human PIG-W protein, which can
      catalyze the inositol acylation of GPI early in the GPI biosynthesis pathway, and
      then we assessed the effects of E1210 on key C. albicans virulence factors. E1210
      inhibited the inositol acylation activity of C. albicans Gwt1p and A. fumigatus
      Gwt1p with 50% inhibitory concentrations (IC(50)s) of 0.3 to 0.6 MUM but had no
      inhibitory activity against human Pig-Wp even at concentrations as high as 100
      MUM. To confirm the inhibition of fungal GPI biosynthesis, expression of ALS1
      protein, a GPI-anchored protein, on the surfaces of C. albicans cells treated
      with E1210 was studied and shown to be significantly lower than that on untreated
      cells. However, the ALS1 protein levels in the crude extract and the RHO1 protein
      levels on the cell surface were found to be almost the same. Furthermore, E1210
      inhibited germ tube formation, adherence to polystyrene surfaces, and biofilm
      formation of C. albicans at concentrations above its MIC. These results suggested
      that E1210 selectively inhibited inositol acylation of fungus-specific GPI which
      would be catalyzed by Gwt1p, leading to the inhibition of GPI-anchored protein
      maturation, and also that E1210 suppressed the expression of some important
      virulence factors of C. albicans, through its GPI biosynthesis inhibition.

PMID- 22143531
TI  - Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria
      tenella.
AB  - Cysteine peptidases have been implicated in the development and pathogenesis of
      Eimeria. We have identified a single-copy cathepsin B-like cysteine peptidase
      gene in the genome database of Eimeria tenella (EtCatB). Molecular modeling of
      the predicted protein suggested that it differs significantly from host enzymes
      and could be a good drug target. EtCatB was expressed and secreted as a soluble,
      active, glycosylated mature enzyme from Pichia pastoris. Biochemical
      characterization of the recombinant enzyme confirmed that it is cathepsin B-like.
      Screening of a focused library against the enzyme identified three inhibitors (a
      nitrile, a thiosemicarbazone, and an oxazolone) that can be used as leads for
      novel drug discovery against Eimeria. The oxazolone scaffold is a novel cysteine
      peptidase inhibitor; it may thus find widespread use.

PMID- 22143532
TI  - Molecular analyses of TEM genes and their corresponding penicillinase-producing
      Neisseria gonorrhoeae isolates in Bangkok, Thailand.
AB  - Neisseria gonorrhoeae is a major public health problem globally, especially
      because the bacterium has developed resistance to most antimicrobials introduced
      for first-line treatment of gonorrhea. In the present study, 96 N. gonorrhoeae
      isolates with high-level resistance to penicillin from 121 clinical isolates in
      Thailand were examined to investigate changes related to their plasmid-mediated
      penicillin resistance and their molecular epidemiological relationships. A beta
      lactamase (TEM) gene variant, bla(TEM-135), that may be a precursor in the
      transitional stage of a traditional bla(TEM-1) gene into an extended-spectrum
      beta-lactamase (ESBL), possibly causing high resistance to all extended-spectrum
      cephalosporins in N. gonorrhoeae, was identified. Clonal analysis using
      multilocus sequence typing (MLST) and N. gonorrhoeae multiantigen sequence typing
      (NG-MAST) revealed the existence of a sexual network among patients from Japan
      and Thailand. Molecular analysis of the bla(TEM-135) gene showed that the
      emergence of this allele might not be a rare genetic event and that the allele
      has evolved in different plasmid backgrounds, which results possibly indicate
      that it is selected due to antimicrobial pressure. The presence of the bla(TEM
      135) allele in the penicillinase-producing N. gonorrhoeae population may call for
      monitoring for the possible emergence of ESBL-producing N. gonorrhoeae in the
      future. This study identified a bla(TEM) variant (bla(TEM-135)) that is a
      possible intermediate precursor for an ESBL, which warrants international
      awareness.

PMID- 22143533
TI  - Correlation of the virological response to short-term maraviroc monotherapy with
      standard and deep-sequencing-based genotypic tropism prediction methods.
AB  - Genotypic tropism testing methods are emerging as the first step before
      prescription of the CCR5 antagonist maraviroc (MVC) to HIV-infected patients in
      Europe. Studies validating genotypic tests have included other active drugs that
      could have potentially convoluted the effects of MVC. The maraviroc clinical test
      (MCT) is an in vivo drug sensitivity test based on the virological response to a
      short-term exposure to MVC monotherapy. Thus, our aim was to compare the results
      of genotypic tropism testing methods with the short-term virological response to
      MVC monotherapy. A virological response in the MCT was defined as a >= 1-log(10)
      decrease in HIV RNA or undetectability after 8 days of drug exposure. Seventy
      three patients undergoing the MCT were included in this study. We used both
      standard genotypic methods (n = 73) and deep sequencing (n = 27) on MCT samples
      at baseline. For the standard methods, the most widely used genotypic algorithms
      for analyzing the V3 loop sequence, geno2pheno and PSSM, were used. For deep
      sequencing, the geno2pheno algorithm was used with a false-positive rate cutoff
      of 3.5. The discordance rates between the standard genotypic methods and the
      virological response were approximately 20% (including mostly patients without a
      virological response). Interestingly, these discordance rates were similar to
      that obtained from deep sequencing (18.5%). The discordance rates between the
      genotypic methods (tropism assays predictive of the use of the CCR5 coreceptor)
      and the MCT (in vivo MVC sensitivity assay) indicate that the algorithms used by
      genotypic methods are still not sufficiently optimized.

PMID- 22143534
TI  - Accumulation of the SET protein in HEK293T cells and mild oxidative stress: cell
      survival or death signaling.
AB  - SET protein (I2PP2A) is an inhibitor of PP2A, which regulates the phosphorylated
      Akt (protein kinase B) levels. We assessed the effects of SET overexpression in
      HEK293T cells, both in the presence and the absence of mild oxidative stress
      induced by 50 MUM tert-butyl hydroperoxide. Immunoblotting assays demonstrated
      that SET accumulated in HEK293T cells and increased the levels of phosphorylated
      Akt and PTEN; in addition, SET decreased glutathione antioxidant defense of cell
      and increased expression of genes encoding antioxidant defense proteins.
      Immunofluorescence analysis demonstrated that accumulated SET was equally
      distributed in cytoplasm and nucleus; however, in cells that had been exposed to
      oxidative stress, SET was found in large aggregates in the cytoplasm. SET
      accumulation in HEK293T cells correlated with inhibition of basal apoptosis as
      evidenced by a decrease in annexin V staining and activity of caspases; under
      mild oxidative stress, SET accumulation correlated with caspase-independent cell
      death, as evidenced by increased PI and annexin V/PI double staining. The results
      suggest that accumulated SET could act via Akt/PTEN either as cell survival
      signal or as oxidative stress sensor for cell death.

PMID- 22143535
TI  - Effect of diallyl trisulfide derivatives on the induction of apoptosis in human
      prostate cancer PC-3 cells.
AB  - The effects of five derivatives of diallyl trisulfide (DATS) were investigated on
      apoptosis in prostate cancer PC-3 cells, including dibutenyl trisulfide (DBTS),
      bis(2-methylallyl) trisulfide (2-M-DATS), dipentenyl trisulfide (DPTS), bis(3
      methylbut-2-enyl) trisulfide (3-M-DBTS), and dihexenyl trisulfide (DHTS). Our
      present study demonstrated that DATS derivatives can suppress proliferation of PC
      3 cells in a dose- and time-dependent manner, and that a change in the DATS
      structure could have an impact on its biological activity in the following order:
      2-M-DATS > DBTS ~ DPTS ~ DATS > 3-M-DBTS ~ DHTS. Typical apoptotic nuclei were
      shown by Hoechst 33342 staining with 80 MUM concentrations of DATS derivatives
      for 24 h. And flow cytometric analysis and DNA fragmentation assay also
      demonstrated that DATS derivatives induced apoptosis in PC-3 cells. Meanwhile,
      experimental results showed that DBTS, 2-M-DATS, and DPTS cause G2-M phase cell
      cycle arrest. Furthermore, a series of apoptosis-associated features were
      observed, which include a notable decrease in the expression of procaspases-3, up
      regulation of pro-apoptotic proteins Bax expression, and down-regulation of anti
      apoptotic proteins Bcl-2 expression in PC-3 cells. All of the evidences above
      indicate that DATS derivatives suppressed proliferation of PC-3 cells which was
      associated with the induction of apoptosis regulated by Bax/Bcl-2.

PMID- 22143536
TI  - Expression of FHL1 in gastric cancer tissue and its correlation with the invasion
      and metastasis of gastric cancer.
AB  - This study was performed to analyze the expression of four and a half LIM domains
      1 (FHL1) in gastric carcinoma tissue and its correlation with the
      clinicopathological characteristics of gastric cancer. In addition, the role of
      FHL1 in the invasion and metastasis of gastric cancer cells was investigated to
      provide an experimental basis for future treatments of gastric cancer. FHL1 mRNA
      and protein expression in gastric carcinoma and the adjacent normal gastric
      mucosa tissue were determined using RT-PCR and western blots. Correlations of
      FHL1 expression with the incidence, progression, and clinicopathological
      characteristics of gastric cancer were analyzed. Changes in the invasion and
      metastatic potential of MKN45 human gastric cancer cells were observed after the
      transient transfection with an eukaryotic expression vector containing full
      length FHL1. Expression of FHL1 mRNA in gastric carcinoma tissue was
      significantly lower than that in the adjacent normal tissue (P < 0.05). FHL1
      expression in gastric carcinoma tissue from patients who were positive for lymph
      node metastasis was significantly lower than those in patients who were negative
      for lymph node metastasis (P < 0.05). Lower FHL1 expression was correlated with
      lower degrees of differentiation, higher TNM stages, and greater invasive
      potential of the gastric cancer (P < 0.05). The FHL1 mRNA and protein expression
      patterns were similar in gastric cancer. FHL1 protein expression in gastric
      carcinoma tissue was significantly lower than that in the surrounding normal
      tissue (P < 0.05). FHL1 protein expression was significantly lower in gastric
      carcinoma tissue from patients who were positive for lymph node metastasis than
      that detected in patients with no lymph node metastasis (P < 0.05). Lower FHL1
      protein expression was correlated with lower degrees of differentiation, higher
      TNM stages, and greater invasive potential in gastric cancer (P < 0.05). However,
      the expression of FHL1 was independent of the patient's gender, age, and tumor
      size (P > 0.05). Overexpression of FHL1 in the MKN45 human gastric cancer cell
      line using an eukaryotic expression vector resulted in a significant reduction in
      the invasiveness and metastatic ability of these cells as determined using the
      Transwell chamber invasion assay (P < 0.05). The decrease in or loss of FHL1
      expression may be related to the incidence, progression, invasiveness, and
      metastatic potential of gastric cancer.

PMID- 22143539
TI  - Development of a process for separation of mogroside V from Siraitia grosvenorii
      by macroporous resins.
AB  - A separation method was developed for the preparative separation and enrichment
      of the non-caloric sweetener mogroside V from Siraitia grosvenorii. The
      adsorption properties of six macroporous resins were evaluated. Results showed
      that HZ 806 resin offered the best adsorption and desorption capacities. Based on
      the adsorption experiments on HZ 806, the adsorption data were found to fit the
      Freundlich model well. The pseudo-second-order kinetic model showed the highest
      correlation with the experimental results. Separation was performed with
      deionized water and 40% aqueous ethanol solution as mobile phases. In a typical
      run, 100 g of herb was processed and 3.38 g of mogroside V with a purity of 10.7%
      was harvested. This separation method provided a 15.1-fold increase in the
      purification factor from 0.5% to 10.7%. The present study showed that HZ 806
      resins were effective for the separation and enrichment of mogroside V from S.
      grosvenorii.

PMID- 22143540
TI  - Antioxidant and antimicrobial attributes and phenolics of different solvent
      extracts from leaves, flowers and bark of Gold Mohar [Delonix regia (Bojer ex
      Hook.) Raf].
AB  - This paper describes the antioxidant and antimicrobial activities and phenolic
      components of different solvent (absolute methanol, absolute ethanol, absolute
      acetone, 80% methanol, 80% ethanol, 80% acetone and deionized water) extracts of
      leaves, flowers and bark of Gold Mohar [Delonix regia (Bojer ex Hook.) Raf.]. The
      extract yields from leaves, flowers and bark ranged from 10.19 to 36.24, 12.97 to
      48.47 and 4.22 to 8.48 g/100 g dry weight (DW), respectively. Overall, 80%
      methanol extract produced from the leaves exhibited significantly (P < 0.05)
      higher antioxidant activity, with high phenolic contents (3.63 g GAE/100 g DW),
      total flavonoid contents (1.19 g CE/100 g DW), inhibition of peroxidation
      (85.54%), DPPH scavenging capacity (IC(50) value 8.89 MUg/mL) and reducing power
      (1.87). Similarly, this 80% methanol leaves extract also showed superior
      antimicrobial activity. HPLC analysis of the 80% methanol extracts for individual
      phenolics revealed the presence of gallic, protocatechuic and salicylic acid in
      leaves; gallic, protocatechuic, salicylic, trans-cinnamic and chlorogenic acid in
      flowers, and gallic acid in bark as the main (amount > 1.50 mg/100 g DW) phenolic
      acids. Besides, small amounts ( < 1.50 mg/100 g DW) of some other phenolic acids
      such as sorbic, sinapic, p-coumaric, m-coumaric, ferulic, caffeic, 3
      hydroxybenzoic, 4-hydroxycinnamic and 4-hydroxybenzoic acids were also detected.
      The extracts of the tested parts of Gold Mohar, especially, the leaves, might be
      valuable for functional food and therapeutic applications.

PMID- 22143541
TI  - Toxicity of Rhododendron anthopogonoides essential oil and its constituent
      compounds towards Sitophilus zeamais.
AB  - The screening of several Chinese medicinal plants for insecticidal principles
      showed that essential oil of Rhododendron anthopogonoides flowering aerial parts
      possessed significant toxicity against maize weevils, Sitophilus zeamais. A total
      of 37 components were identified in the essential oil and the main constituents
      of the essential oil were 4-phenyl-2-butanone (27.22%), nerolidol (8.08%), 1,4
      cineole (7.85%), caryophyllene (7.63%) and gamma-elemene (6.10%), followed by
      alpha-farnesene (4.40%) and spathulenol (4.19%). Repeated bioactivity-directed
      chromatographic separation on silica gel columns led us to isolate three
      compounds, namely 4-phenyl-2-butanone, 1,4-cineole, and nerolidol. 4-Phenyl-2
      butanone shows pronounced contact toxicity against S. zeamais (LD50 = 6.98
      mg/adult) and was more toxic than either 1,4-cineole or nerolidol (LD50 = 50.86
      mg/adult and 29.30 mg/adult, respectively) against the maize weevils, while the
      crude essential oil had a LD50 value of 11.67 mg/adult. 4-Phenyl-2-butanone and
      1,4-cineole also possessed strong fumigant toxicity against the adults of S.
      zeamais (LC50 = 3.80 mg/L and 21.43 mg/L) while the crude essential oil had a
      LC50 value of 9.66 mg/L.

PMID- 22143542
TI  - Chemical, antioxidant and antimicrobial investigations of Pinus cembra L. bark
      and needles.
AB  - The chemical constituents and biological activity of Pinus cembra L. (Pinaceae),
      native to the Central European Alps and the Carpathian Mountains, are not well
      known. The aim of the present work was to examine the phenolic content,
      antioxidant and antimicrobial effects of hydromethanolic extracts of Pinus cembra
      L. bark and needles. Bark extract had higher concentrations of total phenolics
      (299.3 vs. 78.22 mg gallic acid equivalents/g extract), flavonoids (125.3 vs.
      19.84 mg catechin equivalents/g extract) and proanthocyanidins (74.3 vs. 12.7 mg
      cyanidin equivalents/g extract) than needle extract and was more active as a free
      radical scavenger, reducing agent and antimicrobial agent. The EC50 values in the
      2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6
      sulfonic acid) diammonium salt (ABTS) and reducing power assays were 71.1, 6.3
      and 26 mg/mL for bark extract and 186.1, 24 and 104 mg/mL for needle extract,
      respectively. In addition, needle extract showed ferrous ions chelating effects
      (EC50 = 1,755 MUg/mL). The antimicrobial effects against Staphylococcus aureus,
      Sarcina lutea, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and
      Candida albicans were assessed by the agar diffusion method. Both extracts (4
      mg/well) were active against all the microorganisms tested; bark extract showed
      higher inhibition on all strains. These results indicate that Pinus cembra L.
      bark and needles are good sources of phytochemicals with antioxidant and
      antimicrobial activities.

PMID- 22143543
TI  - Synthesis, characterization and fluorescent property evaluation of 1,3,5-triaryl
      2-pyrazolines.
AB  - A series of 1,3,5-triaryl-2-pyrazolines was synthesized by dissolving the
      corresponding 4-alkoxychalcones in glacial acetic acid containing a few drops of
      concentrated hydrochloric acid. This step was followed by the addition of (3,4
      dimethylphenyl) hydrazaine hydrochloride. Finally the target compounds were
      precipitated by pouring the reaction mixture onto crushed ice. The structures of
      the synthesized compounds were established by physicochemical and spectroscopic
      methods. The 1,3,5-triaryl-2-pyrazolines bearing homologous alkoxy groups were
      found to possess fluorescence properties in the blue region of the visible
      spectrum when irradiated with ultraviolet radiation. The fluorescent behavior of
      these compounds was studied by UV-Vis and emission spectroscopy, performed at
      room temperature.

PMID- 22143544
TI  - Camptothecin-20(s)-O-[N-(3'alpha,12'alpha-dihydroxy-24'-carbonyl-5'beta-cholan)]
      lysine, a novel camptothecin analogue, induces apoptosis towards hepatocellular
      carcinoma SMMC-7721 cells.
AB  - Camptothecin-20(s)-O-[N-(3'alpha,12'alpha-dihydroxy-24'-carbonyl-5'beta-cholan)]
      lysine (B2) is a novel camptothecin analogue. Our previous study had shown that
      it displayed higher cytoxicity activity towards hepatocellular carcinoma SMMC
      7721 cells than camptothecin (CPT) in vitro. In this paper, the underlying
      mechanism of anti-proliferation of B2 towards SMMC-7721 cells was further
      examined. Cell growth inhibition of B2 was determined using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; morphological
      changes were observed under Laser Scanning Confocal Microscope (LSCM); cell cycle
      distribution, apoptotic population, changes in mitochondrial membrane potential,
      intracellular calcium concentration and reactive oxygen species (ROS) production
      were determined by flow cytometry (FCM). Activities of caspase-3 and caspase-9
      were measured, and the expression level of Bcl-2 and Bax proteins were analyzed
      by Western blot. The results suggested that B2 inhibited SMMC-7721 cell growth by
      causing cell cycle arrest at the S and G2/M phases, and induced apoptosis
      involving a mitochondrial pathway. B2 appears to cause a high induction of
      apoptosis on SMMC-7721 cells in vitro, which suggests it might be a potential
      drug for cancer therapy.

PMID- 22143545
TI  - Gold-catalyzed cyclizations of alkynol-based compounds: synthesis of natural
      products and derivatives.
AB  - The last decade has witnessed dramatic growth in the number of reactions
      catalyzed by gold complexes because of their powerful soft Lewis acid nature. In
      particular, the gold-catalyzed activation of propargylic compounds has
      progressively emerged in recent years. Some of these gold-catalyzed reactions in
      alkynes have been optimized and show significant utility in organic synthesis.
      Thus, apart from significant methodology work, in the meantime gold-catalyzed
      cyclizations in alkynol derivatives have become an efficient tool in total
      synthesis. However, there is a lack of specific review articles covering the
      joined importance of both gold salts and alkynol-based compounds for the
      synthesis of natural products and derivatives. The aim of this Review is to
      survey the chemistry of alkynol derivatives under gold-catalyzed cyclization
      conditions and its utility in total synthesis, concentrating on the advances that
      have been made in the last decade, and in particular in the last quinquennium.

PMID- 22143546
TI  - One step formation of propene from ethene or ethanol through metathesis on nickel
      ion-loaded silica.
AB  - Increased propene production is presently one of the most significant objectives
      in petroleum chemistry. Especially the one-step conversion of ethene to propene
      (ETP reaction, 3C2H4 ->2C3H6) is the most desired process. In our efforts, nickel
      ion-loaded mesoporous silica could turn a new type of ETP reaction into reality.
      The one-step conversion of ethene was 68% and the propene selectivity was 48% in
      a continuous gas-flow system at 673 K and atmospheric pressure. The reactivity of
      lower olefins and the dependences of the ETP reaction on the contact time and the
      partial pressure of ethene were consistent with a reaction mechanism involving
      dimerization of ethene to 1-butene, isomerization of 1-butene to 2-butene, and
      metathesis of 2-butene and ethene to yield propene. The reaction was then
      expanded to an ethanol-to-propene reaction on the same catalyst, in which two
      possible reaction routes are suggested to form ethene from ethanol. The catalysts
      were characterized mainly by EXAFS and TPR techniques. The local structures of
      the nickel species active for the ETP reaction were very similar to that of
      layered nickel silicate, while those on the inert catalysts were the same as that
      of NiO particles.

PMID- 22143547
TI  - Schiff bases of indoline-2,3-dione: potential novel inhibitors of Mycobacterium
      tuberculosis (Mtb) DNA gyrase.
AB  - In the present study a series of Schiff bases of indoline-2,3-dione were
      synthesized and investigated for their Mtb gyrase inhibitory activity. Promising
      inhibitory activity was demonstrated with some of these derivatives, which
      exhibited IC(50) values ranging from 50-157 mM. The orientation and the ligand
      receptor interactions of such molecules within the Mtb DNA gyrase A subunit
      active site were investigated applying a multi-step docking protocol using
      Molecular Operating Environment (MOE) and Autodock4 docking software. The results
      revealed the importance of the isatin moiety and the connecting side chain for
      strong interactions with the enzyme active site. Among the tested compounds the
      terminal aromatic ring benzofuran showed the best activity. Promising new leads
      for developing a novel class of Mtb gyrase inhibitors were obtained from Schiff
      bases of indoline-2,3-dione.

PMID- 22143548
TI  - Formulation and evaluation of celastrol-loaded liposomes.
AB  - The main purpose of this study was to evaluate the intestinal absorption and the
      antineoplastic effect of the poorly water-soluble drug celastrol when liposomes
      were used as oral drug delivery system. Liposomes were prepared by the ethanol
      injection method. An optimized liposome formulation composed of phospholipid,
      cholesterol and Tween-80 resulted in favorable encapsulation efficiency at 98.06
      +/- 0.94%. Homogeneous and stable particle size of 89.6 +/- 7.3 nm and zeta
      potential of -(87.7 +/- 5.8) mV were determined by laser particle size analyzer.
      Subsequently, the four-site perfusion rat intestinal model revealed that
      celastrol-loaded liposomes had improved effective permeability compared to the
      free drug in four intestinal segments (p < 0.05). Moreover, celastrol-loaded
      liposomes could also inhibit the tumor growth in C57BL/6 mice. These results
      suggest that liposomes could be a promising perioral carrier for celastrol.

PMID- 22143549
TI  - Studies on log Po/w of quinoxaline di-N-oxides: a comparison of RP-HPLC
      experimental and predictive approaches.
AB  - As reported in our previous papers, a series of quinoxaline-2-carboxamide 1,4-di
      N-oxide derivatives were synthesized and studied as anti-tuberculosis agents.
      Here, the capability of the shake-flask method was studied and the retention time
      (expressed as log K) of 20 compounds were determined by RP-HPLC analysis. We
      found that the prediction of log P by the RP-HPLC analysis can result in a high
      accuracy and can replace the shake-flask method avoiding the experimental
      problems presented by quinoxaline di-N-oxides. The studied compounds were
      subjected to the ALOGPS module with the aim of comparing experimental log P(o/w)
      values and predicted data. Moreover, a preliminary in silico screening of the
      QSAR relationship was made confirming the influence of reduction peak potential,
      lipophilicity, H-bond donor capacity and molecular dimension descriptors on anti
      tuberculosis activity.

PMID- 22143550
TI  - Pyrene: a probe to study protein conformation and conformational changes.
AB  - The review focuses on the unique spectral features of pyrene that can be utilized
      to investigate protein structure and conformation. Pyrene is a fluorescent probe
      that can be attached covalently to protein side chains, such as sulfhydryl
      groups. The spectral features of pyrene are exquisitely sensitive to the
      microenvironment of the probe: it exhibits an ensemble of monomer fluorescence
      emission peaks that report on the polarity of the probe microenvironment, and an
      additional band at longer wavelengths, the appearance of which reflects the
      presence of another pyrene molecule in spatial proximity (~10 A). Its high
      extinction coefficient allows us to study labeled proteins in solution at
      physiologically relevant concentrations. The environmentally- and spatially
      sensitive features of pyrene allow monitoring protein conformation,
      conformational changes, protein folding and unfolding, protein-protein, protein
      lipid and protein-membrane interactions.

PMID- 22143551
TI  - Chemical profile of the organic residue from ancient amphora found in the
      Adriatic Sea determined by direct GC and GC-MS analysis.
AB  - An ancient organic residue was collected from the bottom of a Greco-Italian
      amphora found in the Adriatic Sea and investigated by direct GC and GC-MS
      analysis. The headspace composition was determined by HS-SPME using: (1)
      DVB/CAR/PDMS and (2) PDMS/DVB fibres. Higher percentages of benzene derivatives,
      monoterpenes and other low-molecular aliphatic compounds were obtained by method
      (1) in contrast to higher percentage of naphthalene and phenanthrene derivatives
      found by method (2). In comparison with the composition of pine resin, it is more
      likely that the found low-molecular aliphatic alcohols, acids, esters and
      carbonyls with 2-phenylethanol were trapped and preserved within the organic
      residue from stored wine - the amphora's originally content. Semi-volatile
      diterpenes methyl dehydroabietate (33.6%) and retene (24.1%) were dominant in the
      residue CH(2)Cl(2) solution. Other abundant compounds were 1,4
      dimethoxyphenanthrene (6.8%) as well as other naphthalene and/or phenanthrene
      derivatives [7-(1-methylethyl)-1,4a-dimethyl-1,2,3,4,4a,9,10,10a
      octahydronaphthalene, 7-(1-methylethyl)-1,4a-dimethyl-2,3,4,4a,9,10
      hexahydrophenanthrene, 7-(1-methylethyl)-1,4a-dimethyl-1,2,3,4,4a,9,10,10a
      octahydro-phenanthrene, 3,6-dimethylphenanthrene and 2,3,5
      trimethylphenanthrene]. Possible sources and formation pathways of the major
      compounds in the residue were discussed.

PMID- 22143552
TI  - Isolation and purification of oridonin from the whole plant of Isodon rubescens
      by high-speed counter-current chromatography.
AB  - Semi-preparative high-speed counter-current chromatography (HSCCC) was
      successfully used for isolation and purification of oridonin from Isodon
      rubescens by using a two-phase-solvent system composed of n-hexane-ethyl acetate
      methanol-water (2.8:5:2.8:5, v/v/v/v). The targeted compound isolated, collected
      and purified by HSCCC was analyzed by high performance liquid chromatography
      (HPLC). A total of 40.6 mg of oridonin with the purity of 73.5% was obtained in
      less than 100 min from 100 mg of crude Isodon rubescens extract. The chemical
      structure of the compound was identified by IR, 1H-NMR and 13C-NMR.

PMID- 22143553
TI  - Representative seroprevalences of brucellosis in humans and livestock in
      Kyrgyzstan.
AB  - Kyrgyzstan reported 77.5 new human brucellosis cases per 100,000 people in 2007,
      which is one of the highest incidences worldwide. In Kyrgyzstan, the currently
      used diagnostic tests in humans and animals are the Rose Bengal Test and the
      Huddleson test. A national representative cross-sectional study using cluster
      sampling proportional to size in humans, cattle, sheep, and goats was undertaken
      to assess the apparent seroprevalence in humans and animals. A total of 4,936
      livestock sera and 1,774 human sera were tested in Naryn, Chuy, and Osh Oblasts.
      The overall apparent seroprevalences of brucellosis were 8.8% in humans (95% CI
      4.5-16.5), 2.8% (95% CI 1.6-4.9%) in cattle, 3.3% (95% CI 1.5-6.9%) in sheep, and
      2.5% (95% CI 1.4-4.5%) in goats. Naryn Oblast had the highest seroprevalences in
      humans and sheep. More men than women were seropositive (OR = 1.96; P < 0.001).
      Human seroprevalence was significantly associated with small ruminant
      seroprevalence but not with cattle seroprevalence. Annual incidence of human
      brucellosis exposure, measured by serological tests, was more than ten times
      higher than the annual incidence of reported clinical brucellosis cases. This
      indicates an under-reporting of human brucellosis cases, even if only a fraction
      of seropositive people have clinical symptoms. In conclusion, this study confirms
      the high seroprevalence of brucellosis in Kyrgyzstan and warrants rapid effective
      intervention, among others, by mass vaccination of sheep and goats but also of
      cattle.

PMID- 22143554
TI  - Bacterial moonlighting proteins and bacterial virulence.
AB  - Implicit in the central dogma is the hypothesis that each protein gene product
      has but one function. However, over the past decade, it has become clear that
      many proteins have one or more unique functions, over-and-above the principal
      biological action of the specific protein. This phenomenon is now known as
      protein moonlighting and many well-known proteins such as metabolic enzymes and
      molecular chaperones are now recognised as moonlighting proteins. A growing
      number of bacterial species are being found to have moonlighting proteins and the
      moonlighting activities of such proteins can contribute to bacterial virulence
      behaviour. The glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase
      (GAPD) and enolase, and the cell stress proteins: chaperonin 60, Hsp70 and
      peptidyl prolyl isomerase, are among the most common of the bacterial
      moonlighting proteins which play a role in bacterial virulence. Moonlighting
      activities include adhesion and modulation of cell signalling processes. It is
      likely that only the tip of the bacterial moonlighting iceberg has been sighted
      and the next decade will bring with it many new discoveries of bacterial
      moonlighting proteins with a role in bacterial virulence.

PMID- 22143555
TI  - Employment status and perceived health status in younger and older people with
      multiple sclerosis.
AB  - This study explores how employment is associated with perceived physical and
      mental health status in people with multiple sclerosis (MS) adjusted for
      sociodemographic and clinical variables stratified by age. The sample consisted
      of 184 MS patients divided into a younger (<45 years) and an older (>=45 years)
      age group. Respondents underwent an interview, a neurological examination on
      disability [Expanded Disability Status Scale (EDSS)], and completed the Short
      Form-36 Health Survey. Of the respondents (mean age 40.5+/-6.2 years), 43.5% were
      employed. Significant differences between younger and older patients were found
      in employment, EDSS, disease duration, and five Short Form-36 Health Survey
      dimensions. Block-step multiple regression explained 32.4% of the variance in
      physical health and 14.5% in mental health in the younger group. Being employed
      was significantly related to good physical health, whereas EDSS diminished the
      effect of being employed on physical health. The most important variable for
      mental health was employment status in the younger group. For the older age
      group, 19.1% of the variance in physical health and 14.0% of the variance in
      mental health was explained by the studied variables. Male gender and a lower
      EDSS were significant explanatory variables of better physical health. Male
      gender significantly explained mental health in the older age group. In
      conclusion, employment status was an explanatory variable for physical health and
      mental health in the younger patients. EDSS played a significant role in physical
      health for all patients. A vocational rehabilitation program could prevent
      eventual nonemployment and improve health outcomes in older MS people.

PMID- 22143556
TI  - Mouse hepatoma cell lines differing in aryl hydrocarbon receptor-mediated
      signaling have different activities for glucuronidation.
AB  - For studies on the aryl hydrocarbon receptor (AhR)-dependent toxicity of the
      mycotoxins alternariol (AOH) and alternariol methyl ether (AME), three mouse
      hepatoma (Hepa-1) cell lines with intact and with compromised AhR signaling were
      compared with respect to their activities for hydroxylation, methylation, and
      glucuronidation. Whereas the activities of cytochrome P450-mediated monooxygenase
      and catechol-O-methyl transferase were very low and did not differ between the
      three cell lines, a pronounced difference was observed for UDP-glucuronosyl
      transferase activity, which was much higher in Hepa-1c1c4 than in c1c7 and c1c12
      cells. In all three cell types, the rate of glucuronidation of AOH was about four
      times higher than that of AME. Whereas AME caused a concentration-dependent G2/M
      arrest in each cell line, AOH arrested Hepa-1c1c7 and c1c12 cells but not c1c4
      cells. However, Hepa-1c1c4 cells were arrested by AOH when beta-glucuronidase was
      added to the incubation medium in order to reverse the formation of AOH
      glucuronides. We conclude that the failure of AOH to cause cell cycle inhibition
      in Hepa-1c1c4 cells is due to its efficient glucuronidation. The considerable UDP
      glucuronosyl transferase activity of Hepa-1c1c4 cells should be taken into
      account when other compounds are studied in this cell line. Moreover, we
      demonstrate that differences in glucuronide formation between cell types can be
      overcome by the addition of beta-glucuronidase to the cell culture medium.

PMID- 22143557
TI  - Peripunctal melanocytic nevus.
AB  - We report a case of a 37-year-old male with a conjunctival melanocytic nevus
      presenting in a rare, peripunctal location with preservation of the lacrimal
      canaliculus and punctum.

PMID- 22143558
TI  - [Pancarpal arthrodesis using a "CastLess Plate" in dogs and cats].
AB  - OBJECTIVE: Description of clinical experience with a new implant for dorsal
      plating in pancarpal arthrodesis. MATERIAL UND METHODS: Retrospective analysis
      (June 2008 - May 2009) of clinical records from a heterogenous group of dogs and
      cats which where treated by pancarpal arthrodesis using a PCA-plate ("CastLess
      plate", Orthomed(r), UK). RESULTS: In 15 dogs and three cats, a total of 20
      pancarpal arthrodesis (complete fusion of carpal joints) using a PCA-plate were
      performed. External coaptation by cast was not used in the postoperative period.
      In two out of 17 arthrodesis in 15 dogs serious postoperative complications
      (plate deformation, wound infection) occurred which required a revision surgery.
      Fistula formation (8-16 weeks post surgery) was seen in six arthrodesis. They all
      resolved after medical therapy. In cats, all three arthrodesis showed
      postoperative complications (bone resorption under the plate n=1, paw swelling
      n=2). Long-term evaluation by telephone interview with the owners (17 owners, 6
      21 months after surgery, one case lost in follow-up) revealed good or very good
      results for 17 of 19 arthrodesis. CLINICAL RELEVANCE: Pancarpal arthrodesis in
      dogs can be performed successfully using the "CastLess Plate" without additional
      external coaptation. Due to the size of the available implants complications have
      to be expected in cats.

PMID- 22143559
TI  - [Clinical and laboratory-diagnosed parameters in 21 dogs with primary immune
      mediated thrombocytopenia].
AB  - OBJECTIVE: Characterization of clinical and clinicopathological parameters as
      well as the treatment and course of the disease in dogs with suspected primary
      immune-mediated thrombocytopenia (pIMT), and identification of characteristics in
      comparison to secondary IMT (sIMT). MATERIAL AND METHODS: Medical records of
      thrombocytopenic dogs with a positive platelet-bound-antibody (PBA)-test
      performed between 2003 and 2008 were evaluated retrospectively. Dogs were
      suspected of having pIMT by exclusion of other diseases potentially associated
      with sIMT, and sIMT was diagnosed when an associated disease could be detected.
      Dogs with an incomplete follow-up were excluded from the study. RESULTS: Thirteen
      of 21 dogs (62%) suspected of having pIMT were male. Median age of the affected
      dogs was 6.6 years (1.6-13.5 years [MINIMUM-maximum]). Spontaneous bleeding was
      observed in 18 dogs (86%) mainly in the form of surface bleeding. Nineteen dogs
      (91%) with pIMT had platelet counts below 20,000/MUl. All dogs with pIMT, for
      which platelet volume analysis was available, displayed a mean platelet volume
      (MPV) within or below the reference range. Fourteen of 15 dogs in which bone
      marrow analysis was performed had an increased megakaryopoiesis. Comparison of
      two different treatment regimes (prednisolone versus prednisolone and
      azathioprine) did not result in a significantly different platelet count recovery
      time. There was no significant difference regarding age and sex distribution
      between dogs with pIMT and sIMT. Platelet count and MPV were significantly lower
      in dogs with pIMT than in dogs with sIMT. Increased megakaryopoiesis was more
      frequently detected in dogs with pIMT compared to dogs with sIMT. CONCLUSION AND
      CLINICAL RELEVANCE: Dogs with a positive PBA-test and additionally a severe
      thrombocytopenia, low MPV and activated megakaryopoiesis are likely to have pIMT.

PMID- 22143560
TI  - Effect of prednisolone and cetirizine on D. farinae and histamine-induced wheal
      and flare response in healthy dogs.
AB  - OBJECTIVE: Prednisolone and antihistamines are highly potent drugs in the
      treatment of atopic dermatitis and widely used in humans and dogs. In some atopic
      patients in which antihistamines, corticosteroids or other drugs have already
      been administered intradermal testing (IDT) may be necessary. The aim of the
      present study was to compare the effects of cetirizine and prednisolone on IDT
      results. MATERIAL AND METHODS: Thirty healthy dogs (average age 5.9 +/- 0.6
      years) were randomly assigned to three groups. Treatment groups were administered
      prednisolone (1 mg/kg BW daily, tapering dosage; group I), cetirizine (1mg/kg BW
      daily; group II) and placebo (group III) respectively for one week. In the second
      week, none of the dogs received any medications. IDT was performed prior to drug
      administration and results obtained were considered as the baseline response.
      Second and third IDTs were performed at the end of the first and second week,
      respectively. RESULTS: In groups I and II IDT reactivity was reduced at the end
      of first week (p<0.05). After drug discontinuation the reactivity almost returned
      to baseline at the end of the 2-week period, with the exception of the
      prednisolone group for D.farinae . CONCLUSION: Prednisolone and cetirizine have
      significant effects on IDT reactions and must be withdrawn by veterinary
      practitioners up to 2 weeks prior to IDT.

PMID- 22143561
TI  - [Climate change - a pioneer for the expansion of canine vector-borne diseases?].
AB  - Vector-transmitted diseases are one of the major contributors to the global
      burden of disease in humans and animals. Climate change is consistently held
      responsible for the spread of parasitic acarid and insect vectors such as ticks,
      fleas, sand flies and mosquitoes, and their transmitted pathogens (in the case of
      the dog the so-called canine vector-borne diseases [CVBD]). Currently, there is
      only insufficient data available to prove whether climate change is a major
      driving force for vector and disease expansion, but the evidence is growing.
      Other reasons, such as ecological, demographic and socio-economic factors, e.g.
      pet travel into and pet import from endemic areas, also play a role in this
      development. Apart from all the controversial discussion of the factors leading
      to vector and disease expansion, preventative measures should include dog owners'
      education as they are responsible for individual parasite protection as well as
      for the minimisation of adverse risk behaviour, e.g. regarding pet travel. Broad
      spectrum vector control should be practised by using parasiticides that repel and
      kill blood feeders in order to minimize the risk of CVBD-pathogen transmission.

PMID- 22143562
TI  - [Juvenile dilated cardiomyopathy in a Labrador Retriever].

PMID- 22143563
TI  - [Malignant melanophoroma in a Hermann's tortoise (Testudo hermanni). A case
      report].

PMID- 22143564
TI  - [Radiological findings of inflammatory and neoplastic spinal column changes in
      the dog and cat].

PMID- 22143565
TI  - Cut and paste: restoring cellular function by gene correction.

PMID- 22143566
TI  - Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem
      cells through promoting the proliferation of cardiac progenitor cells.
AB  - Generation of induced pluripotent stem cells (iPSCs) has opened new avenues for
      the investigation of heart diseases, drug screening and potential autologous
      cardiac regeneration. However, their application is hampered by inefficient
      cardiac differentiation, high interline variability, and poor maturation of iPSC
      derived cardiomyocytes (iPS-CMs). To identify efficient inducers for cardiac
      differentiation and maturation of iPSCs and elucidate the mechanisms, we
      systematically screened sixteen cardiomyocyte inducers on various murine (m)
      iPSCs and found that only ascorbic acid (AA) consistently and robustly enhanced
      the cardiac differentiation of eleven lines including eight without spontaneous
      cardiogenic potential. We then optimized the treatment conditions and
      demonstrated that differentiation day 2-6, a period for the specification of
      cardiac progenitor cells (CPCs), was a critical time for AA to take effect. This
      was further confirmed by the fact that AA increased the expression of
      cardiovascular but not mesodermal markers. Noteworthily, AA treatment led to
      approximately 7.3-fold (miPSCs) and 30.2-fold (human iPSCs) augment in the yield
      of iPS-CMs. Such effect was attributed to a specific increase in the
      proliferation of CPCs via the MEK-ERK1/2 pathway by through promoting collagen
      synthesis. In addition, AA-induced cardiomyocytes showed better sarcomeric
      organization and enhanced responses of action potentials and calcium transients
      to beta-adrenergic and muscarinic stimulations. These findings demonstrate that
      AA is a suitable cardiomyocyte inducer for iPSCs to improve cardiac
      differentiation and maturation simply, universally, and efficiently. These
      findings also highlight the importance of stimulating CPC proliferation by
      manipulating extracellular microenvironment in guiding cardiac differentiation of
      the pluripotent stem cells.

PMID- 22143567
TI  - Defective heart development in hypomorphic LSD1 mice.
AB  - Lysine-specific demethylase 1 (LSD1/AOF2/KDM1A), the first enzyme with specific
      lysine demethylase activity to be described, demethylates histone and non-histone
      proteins and is essential for mouse embryogenesis. LSD1 interacts with numerous
      proteins through several different domains, most notably the tower domain, an
      extended helical structure that protrudes from the core of the protein. While
      there is evidence that LSD1-interacting proteins regulate the activity and
      specificity of LSD1, the significance and roles of such interactions in
      developmental processes remain largely unknown. Here we describe a hypomorphic
      LSD1 allele that contains two point mutations in the tower domain, resulting in a
      protein with reduced interaction with known binding partners and decreased
      enzymatic activity. Mice homozygous for this allele die perinatally due to heart
      defects, with the majority of animals suffering from ventricular septal defects.
      Transcriptional profiling revealed altered expression of a limited subset of
      genes in the hearts. This includes an increase in calmodulin kinase (CK) 2beta,
      the regulatory subunit of the CK2 kinase, which correlates with E-cadherin
      hyperphosphorylation. These results identify a previously unknown role for LSD1
      in heart development, perhaps partly through the control of E-cadherin
      phosphorylation.Cell Research advance online publication 6 December 2011;
      doi:10.1038/cr.2011.194.

PMID- 22143569
TI  - Surgical treatment and management of hip fracture patients.
AB  - INTRODUCTION: Osteoporosis-related hip fractures are associated with high
      mortality and costs. The optimum type of treatment for such fractures is
      controversial. To shed some light on this issue, the surgical treatment and
      management of osteoporotic hip fractures were discussed during a hip fracture
      surgical working group at the 2009 International Society For Fracture Repair
      Annual Meeting comprising leading experts in the field. MATERIALS AND METHODS:
      The working group consisted of eight orthopaedic surgeons, six industry
      representatives and one research scientist. Eleven participants were from Europe
      and four were from the USA and Canada. Two chairmen posed 12 questions relating
      to the surgical treatment and management of osteoporotic hip fractures. Each
      question was discussed and key points were noted. RESULTS: Surgery should
      commence within 24-48 h but the patient should be optimized if presenting with
      >=3 comorbidities. Specialized centres integrating orthopaedics, geriatricians
      and rheumatologists could be a solution for the lack of specialist care post
      surgery. Surgical technique is important in fracture fixation, as is the implant,
      but there has been no improvement in implant design in the past 50 years. As a
      consequence, malunion has become unjustifiably accepted. Fracture healing can be
      accelerated using pharmaceuticals which are also important in secondary
      prophylaxis. All displaced femoral neck fractures in geriatric patients should be
      treated with hip replacement, the choice between using cemented or uncemented
      fixation being at the surgeon's discretion. DISCUSSION AND CONCLUSION: This
      working group discussion highlighted several important issues which could be of
      interest to the orthopaedic community.

PMID- 22143571
TI  - Tertiary alkylamines as nucleophiles in substitution reactions at heteroaromatic
      halide during the synthesis of the highly potent pirinixic acid derivative 2-(4
      chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)octanoic acid (YS-121).
AB  - YS-121 [2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)octanoic acid]
      is the result of target-oriented structural derivatization of pirinixic acid. It
      is a potent dual PPARalpha/gamma-agonist, as well as a potent dual 5-LO/mPGES-1
      inhibitor. Additionally, recent studies showed an anti-inflammatory efficacy in
      vivo. Because of its interference with many targets, YS-121 is a promising drug
      candidate for the treatment of inflammatory diseases. Ongoing preclinical studies
      will thus necessitate huge amounts of YS-121. To cope with those requirements, we
      have optimized the synthesis of YS-121. Surprisingly, we isolated and
      characterized byproducts during the resulting from nucleophilic aromatic
      substitution reactions by different tertiary alkylamines at a heteroaromatic
      halide. These amines should actually serve as assisting bases, because of their
      low nucleophilicity. This astonishing fact was not described in former
      publications concerning that type of reaction and, therefore, might be useful for
      further reaction improvement in general. Furthermore, we could develop a proposal
      for the mechanism of that byproduct formation.

PMID- 22143568
TI  - Signal control through Raf: in sickness and in health.
AB  - The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade is the prototype
      mammalian mitogen-activated protein kinase (MAPK) signaling cascade that
      regulates a number of processes, including proliferation, differentiation,
      survival, migration, stress responses and apoptosis. How this seemingly linear
      cascade is modulated to achieve a specific cellular function has been a main
      focus of the field. In this review, we describe new as well as old findings in
      the regulation of the ERK1/2 pathway in normal and disease states via MAP3Ks.

PMID- 22143572
TI  - Extraction of Lepidium apetalum seed oil using supercritical carbon dioxide and
      anti-oxidant activity of the extracted oil.
AB  - The supercritical fluid extraction (SFE) of Lepidium apetalum seed oil and its
      anti-oxidant activity were studied. The SFE process was optimized using response
      surface methodology (RSM) with a central composite design (CCD). Independent
      variables, namely operating pressure, temperature, time and flow rate were
      evaluated. The maximum extraction of Lepidium apetalum seed oil by SFE-CO2 (about
      36.3%) was obtained when SFE-CO2 extraction was carried out under the optimal
      conditions of 30.0 MPa of pressure, 70  degrees C of temperature, 120 min of
      extraction time and 25.95 L/h of flow rate. GC-MS analysis showed the presence of
      four fatty acids in Lepidium apetalum seed oil, with a high content (91.0%) of
      unsaturated fatty acid. The anti-oxidant activity of the oil was assessed by the
      2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay and 2,2'-azino-
      bis(3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS) test. Lepidium
      apetalum seed oil possessed a notable concentration-dependent antioxidant
      activity, with IC50 values of 1.00 and 3.75 mg/mL, respectively.

PMID- 22143573
TI  - Changes in morphology and activity of transglutaminase following cross-linking
      and immobilization on a polypropylene microporous membrane.
AB  - Transglutaminase (TGase) was cross-linked with glutaraldehyde, and cross-linked
      crystalline transglutaminase was immobilized on a polypropylene microporous
      membrane by UV-induced grafting. Immobilized enzyme activity were calculated to
      be 0.128 U/cm2 polypropylene microporous membrane. The microstructure and enzyme
      characteristics of free, cross-linked and immobilized transglutaminase were
      compared. The optimum temperature of free transglutaminase was determined to be
      approximately 40  degrees C, while cross-linking and immobilization resulted in
      an increase to approximately 45  degrees C and 50  degrees C. At 60  degrees C,
      immobilized, cross-linked and free transglutaminase retained 91.7 +/- 1.20%, 63.2
      +/- 1.05% and 37.9 +/- 0.98% maximum activity, respectively. The optimum pH was
      unaffected by the state of transglutaminase. However, the thermal and pH
      stabilities of cross-linked and immobilized transglutaminase were shown to
      increase.

PMID- 22143575
TI  - Comparison between preoperative versus intraoperative injection of technetium-99
      m neomannosyl human serum albumin for sentinel lymph node identification in early
      stage lung cancer.
AB  - PURPOSE: We aimed to evaluate the results of sentinel lymph node mapping
      according to injection time (preoperative vs. intraoperative) of technetium-99m
      neomannosyl human serum albumin (99mTc-MSA) in patients with lung cancer.
      METHODS: Data of 82 patients (55 men; mean age 62.9+/-9.3 years) who were
      candidates for lobectomy with mediastinal lymph node dissection for clinical
      stage I non-small cell lung cancer were retrospectively reviewed. (99m)Tc-MSA was
      administered at the peritumoral region under chest computed tomographic guidance,
      1 to 2 h before surgery (preoperation group, n=48) or soon after thoracotomy
      (intraoperation group, n=34). RESULTS: Patients' demographic data, except type of
      operation, did not differ between the two groups. Sentinel lymph nodes were
      detected in 46 patients (95.8%) in the preoperation group and 33 patients (97.1%)
      in the intraoperation group (P=.243). The mean number of sentinel nodes per
      patient was 2.1 in the preoperation group and 2.6 in the intraoperation group
      (P=.068). No falsely negative sentinel nodes were detected in any of the 17
      patients with N1 or N2 disease (0%) in either group. Administration of the
      intraoperative injection could save additional cost (US$607) and time (70 min) in
      each patient. CONCLUSIONS: Sentinel node identification using 99mTc-MSA appears
      to provide similar excellent results in both preoperative and intraoperative
      injection. Therefore, intraoperative injection of 99mTc-MSA may be preferred as a
      result of lower cost and less waste of time.

PMID- 22143576
TI  - A multi-institutional experience of repeat regional chemotherapy for recurrent
      melanoma of extremities.
AB  - BACKGROUND: Hyperthermic isolated limb perfusion (HILP) or isolated limb infusion
      (ILI) are well-accepted regional chemotherapy techniques for in-transit melanoma
      of extremity. The role and efficacy of repeat regional chemotherapy for
      recurrence and which salvage procedure is better remains debatable. We aimed to
      compare toxicities and clinical outcomes by procedure types and the sequence.
      METHODS: Data from 44 patients, who underwent repeat HILPs or ILIs from 3
      institutions beginning 1997 to 2010, were retrospectively reviewed. Regional
      toxicity assessed by Wieberdink grade, systemic toxicity assessed by serum
      creatine phosphokinase level, length of hospital stay (LOS), response rates at 3
      months after the procedure, and time to in-field progression (TTP) were analyzed.
      RESULTS: Of 44 patients, 46% were men and 54% women with a median age of 66
      (range 29-85) years at diagnosis. The median follow-up was 21.4 (range 4-153)
      months. Of 70 ILIs and 28 HILPs, the following groups were identified: group A,
      ILI -> ILI (n = 25); group B, ILI -> HILP (n = 10); group C, HILP -> ILI (n =
      12); and group D, HILP -> HILP (n = 3). The comparison of Wieberdink grade, serum
      creatine phosphokinase level, LOS, and response rate between procedures (HILP vs.
      ILI), between sequence (initial vs. repeat), and among their interactions showed
      no statistically significant differences. TTP after initial procedure did not
      differ between HILP and ILI (P = 0.08), and no survival difference was seen (P =
      0.65) when TTP after repeat procedure was compared. CONCLUSIONS: Most patients
      tolerated repeat regional chemotherapy without increased toxicity or LOS. No
      statistical difference in clinical outcomes was noted when comparing repeat
      procedures, even though repeat HILPs showed higher complete response compared to
      repeat ILIs.

PMID- 22143577
TI  - Surveillance of pancreatic cancer patients after surgical resection.
AB  - BACKGROUND: There are no clear recommendations to guide posttreatment
      surveillance in patients with pancreatic cancer. Our goal was to describe the
      posttreatment surveillance patterns in patients undergoing curative-intent
      resection for pancreatic cancer. METHODS: We used Surveillance, Epidemiology, and
      End Results (SEER)-Medicare linked data (1992-2005) to identify CT scans and
      physician visits in patients with pancreatic cancer who underwent curative
      resection (n = 2393). Surveillance began 90 days after surgery, and patients were
      followed for 2 years at 6-month intervals. Patients were censored if they died,
      experienced recurrence of disease, or entered hospice. RESULTS: A total of 2045
      patients survived uncensored to the beginning of the surveillance period. CT scan
      use decreased from 20.9% of patients in month 4 to 6.4% in month 27. There was no
      temporal pattern in CT use to suggest regular surveillance. Twenty-three percent
      of patients did not receive a CT scan in the year after surgery, increasing to
      42% the second year. Patients who underwent adjuvant therapy and patients
      diagnosed in later years had higher CT scan use over the surveillance periods.
      Most patients visited both a primary care physician and a cancer specialist in
      each 6-month surveillance period. Patients who visited cancer specialists were
      more likely to have any CT scan and to be scanned more frequently. CONCLUSIONS:
      Current surveillance patterns after resection for pancreatic cancer reflect the
      lack of established guidelines, implying a need for evaluation and
      standardization of surveillance protocols. The lack of a temporal pattern in CT
      testing suggests that most were obtained to evaluate symptoms rather than for
      routine surveillance.

PMID- 22143578
TI  - Risk factors for peritoneal recurrence in stage II/III gastric cancer patients
      who received S-1 adjuvant chemotherapy after D2 gastrectomy.
AB  - BACKGROUND: The peritoneum is still the most frequent site of recurrence in stage
      II/III gastric cancer patients, although the survival rate was improved by the
      introduction of S-1 adjuvant chemotherapy. The objective of this retrospective
      study was to clarify the risk factors for peritoneal recurrence in patients who
      received S-1 adjuvant chemotherapy. METHODS: Peritoneal recurrence-free survival
      was examined in 100 gastric cancer patients who underwent curative D2 surgery,
      which were diagnosed with stage II or III disease pathologically, and received
      adjuvant S-1 between June 2002 and March 2011. The univariate and multivariate
      analyses were performed to identify risk factors by a Cox proportional hazards
      analysis. RESULTS: The P-RFS was 64.3% at 3 years and 58.8% at 5 years. A total
      of 18 patients were diagnosed with peritoneal recurrence. The macroscopic tumor
      diameter, depth of tumor invasion, and lymph node metastasis were the significant
      factors identified by the univariate analysis, while the tumor diameter and lymph
      node metastasis were the only significant independent risk factors identified by
      the multivariate analysis. CONCLUSIONS: The macroscopic tumor diameter and
      presence of lymph node metastasis were the most important risk factors for
      peritoneal recurrence. When patients had these risk factors, S-1 was not
      sufficient to inhibit peritoneal recurrence. A novel adjuvant chemotherapeutic
      agent targeting peritoneal metastasis in these patients should be developed.

PMID- 22143579
TI  - Activation of the G-protein-coupled receptor GPR30 induces anxiogenic effects in
      mice, similar to oestradiol.
AB  - RATIONALE: The influence of ovarian hormones on behaviour is well accepted, and
      oestrogen replacement therapy has proven to be beneficial in several cases of
      menopausal mood disorders. However, there are also some adverse effects of such a
      therapy, like anxiety and dysphoria. In fact, some women feel better at low
      levels of oestrogen and worse when levels fluctuate. Still, it is unclear which
      receptors might mediate negative emotional effects. OBJECTIVES: The aim of this
      study was to identify which oestrogen receptor(s) are capable of mediating
      negative emotional effects and, therefore, may represent candidates responsible
      for the adverse side effects observed in oestrogen replacement therapy. RESULTS:
      We provide evidence from mouse behavioural tests that oestrogen-induced
      anxiogenic-like effects might be mediated, at least in part, by the G protein
      coupled receptor GPR30. The short-term application of specific agonists against
      the alpha and beta oestrogen receptors did not result in marked behavioural
      changes. In contrast, the specific stimulation of GPR30 in male and
      ovariectomized female mice induced anxiogenic effects. The anxiogenic effects
      induced by the specific GPR30 agonist G-1 were comparable (and non-accumulative)
      to those observed after low doses of the general oestrogen receptor agonist 17b
      oestradiol in male mice, thereby reflecting the behavioural changes observed in
      intact female mice during early pro-oestrus. CONCLUSIONS: Our data suggest that
      GPR30 induces acute anxiogenic effects of oestrogen in rodents. It is tempting to
      speculate that a potential imbalance in the expression of the anxiolytic beta
      oestrogen receptor and the anxiogenic GPR30 may also be involved in the negative
      symptoms of oestrogen replacement therapy in humans.

PMID- 22143581
TI  - hbeta2R-Galphas complex: prediction versus crystal structure--how valuable are
      predictions based on molecular modeling studies?
AB  - In 2010, we predicted two models for the hbeta(2)R-Galpha(s) complex by combining
      the technique of homology modeling with a potential energy surface scan, since a
      complete crystal structure of the hbeta(2)R-Galpha(s) complex was not available.
      The crystal structure of opsin co-crystallized with part of the C-terminus of
      Galpha (3DQB) was used as a template to model the hbeta(2)R, whereas the crystal
      structure of Galpha (1AZT) was used as a template to model Galpha(s). Utilizing a
      potential energy surface scan between hbeta(2)R and Galpha(s), a six-dimensional
      potential energy surface was obtained. Two significant minimum regions were
      located on this surface, and each was associated with a distinct hbeta(2)R
      Galpha(s) complex, namely model I and model II [Strabetaer A, Wittmann H-J (2010)
      J Mol Model 16:1307-1318]. The crystal structure of the hbeta(2)R
      Galpha(s)betagamma complex has recently been published. Thus, the aim of the
      current study was, on the one hand, to compare our predicted structures with the
      true crystal structure, and on the other to discuss the question: how valuable
      are predictions based on molecular modeling studies?

PMID- 22143580
TI  - Effects of protein kinase A inhibitor and activator on rewarding effects of SKF
      82958 microinjected into nucleus accumbens shell of ad libitum fed and food
      restricted rats.
AB  - RATIONALE: Previous studies indicate that the rewarding effect of D-1 dopamine
      receptor stimulation in nucleus accumbens (NAc) shell is greater in food
      restricted (FR) than in ad libitum fed (AL) rats. The D-1 receptor is positively
      coupled to adenylyl cyclase and activates protein kinase A (PKA). OBJECTIVES: The
      purpose of this study was to determine whether PKA is involved in the rewarding
      effect of D-1 receptor stimulation and, if so, whether it is involved in the
      enhanced response of FR rats. MATERIALS AND METHODS: Rats were stereotaxically
      implanted with microinjection cannulae in NAc shell and a stimulating electrode
      in lateral hypothalamus. The rewarding effects of SKF-82958 (1.5 or 3.0 MUg,
      bilaterally) in the presence and absence of PKA inhibitor, Rp-cAMPS (8.9 MUg),
      and PKA activator, Sp-cAMPS (8.9 MUg), were assessed using the curve-shift method
      of intracranial self-stimulation (ICSS). Basal NAc levels of DARPP-32
      phosphorylated on Thr34 and Thr75 were measured. RESULTS: Rp-cAMPS increased the
      rewarding effect of SKF-82958 in AL but not FR rats, doubling the ICSS threshold
      lowering effect of the 3.0-MUg dose. Sp-cAMPS decreased the rewarding effect of
      SKF-82958 in FR but not AL rats. Levels of phospho-DARPP-32 (Thr75), which
      inhibits PKA, were higher in FR than AL rats. CONCLUSIONS: Results indicate that
      inhibition of PKA enhances the unconditioned rewarding effect of D-1 receptor
      stimulation and that decreased PKA may be involved in the effect of FR on drug
      reward. Evidence for involvement of D-2 receptor-expressing neurons in the
      enhancing effect of PKA inhibition is discussed.

PMID- 22143582
TI  - Analysis of hearing improvement in patients with severe to profound sudden
      sensorineural hearing loss according to the level of pure tone hearing threshold.
AB  - Patients with profound sudden sensorineural hearing loss (SSNHL) have a poor
      prognosis regardless of the type of treatment they receive. However, there is
      evidence that a proportion of patients with profound hearing loss may exhibit
      variable degrees of recovery, and this has yet to be specifically investigated.
      Here, we report a comparison of levels of hearing improvement in patients
      stratified according to their level of hearing threshold before treatment. We
      divided patients with severe to profound SSNHL into three groups: patients with
      an initial hearing threshold of 80-89 dB (n = 18), 90-99 dB (n = 16), and >=100
      dB (n = 34). We compared improvements in hearing threshold at different
      frequencies and recovery rates between the three groups. No significant
      differences were observed in hearing threshold improvements at different
      frequencies in the three groups after treatment. However, in the group with an
      initial hearing threshold of >=100 dB, significantly less complete and partial
      recoveries occurred compared to those in the 80-89 or 90-99 dB groups. Our
      results suggest that initial hearing threshold in excess of 100 dB alters the
      likelihood of satisfactory recovery in patients with severe to profound SSNHL.

PMID- 22143583
TI  - Transoral robotic surgery for head and neck carcinomas.
AB  - The objective of this study was prospectively to assess the feasibility and
      safety of transoral robotic surgery (TORS) in head and neck carcinomas and to
      report our learning curve and 2-year outcomes. Patients with oropharyngeal,
      hypopharyngeal and laryngeal tumors treated with TORS were prospectively
      included. We evaluated: the feasibility of TORS, robotic set-up time, transoral
      robotic surgery time, blood loss, surgical margins, tracheotomy, feeding tube,
      time to oral feeding and surgery-related complications. Twenty-three patients
      were treated for 25 carcinomas. Twenty-two patients underwent successful robotic
      resection for 24 carcinomas (96%). One patient required conversion to open
      surgery due to massive bleeding. The mean robotic set-up time was 25 min (range:
      15-100 min) and mean TORS operating time was 70 min (range: 20-150 min). Positive
      margin of resection was observed in one patient (classified pT3) out of the 24
      cancers and was managed by postoperative chemoradiation. No tracheotomy was
      performed. Three patients required prolonged intubation for a mean of 22 h. Two
      patients required a temporary gastrostomy (for 2 and 3.5 months, respectively).
      All other patients resumed oral feeding between the first and third postoperative
      day. The mean hospital stay was 6.4 days (range: 4-19 days). No postoperative
      complication occurred. Mean follow-up was 20 months (median: 19, range: 14-26).
      No death and no case of local or metastatic failure were observed. TORS is
      feasible and safe for the resection of selected head and neck carcinomas. The
      occurrence of intraoperative bleeding emphasizes the need for surgeons to be
      skilled in both transoral and open approaches.

PMID- 22143584
TI  - [Measuring myocardial velocity using tissue Doppler imaging in healthy dogs].
AB  - OBJECTIVE: of the study was to evaluate tissue velocity imaging (TVI) with
      respect to its reproducibility and to introduce reference values in a large
      canine population. In addition, the influence of gender, heart rate, age, weight
      and breed of the dogs was evaluated. MATERIAL AND METHODS: A total of 199 healthy
      dogs were included. The longitudinal TVI was recorded from an apical four-chamber
      view using colour Doppler technique in unsedated dogs. Each myocardial wall was
      recorded as a single wall image, aligning the ultrasound beam as parallel as
      possible to the longitudinal motion of the respective wall. Off-line analysis was
      performed using the Q-analysis software. RESULTS: Coefficients of variance for
      intrareader and interreader variability for each parameter were less than 10.0%
      and 12.4%, respectively. Tissue velocities were heterogeneously distributed
      within the myocardium, demonstrating an apico-basal gradient. Whereas gender did
      not influence TVI variables, heart rate, age, breed and weight had a significant
      influence on the tissue velocity. CONCLUSION AND CLINICAL RELEVANCE: TVI is a
      sophisticated and promising echocardiographic technique. It is relatively easy to
      perform and can be included in the evaluation of systolic and diastolic
      myocardial function in routine daily practice. One limitation is that it is
      influenced by heart rate, age, breed and weight of the dogs. This study provides
      a basis for further investigation on this topic and supplies reference values for
      different weight groups in dogs.

PMID- 22143585
TI  - [Magnetic resonance imaging of the temporomandibular joint in dogs and cats.
      Effect of different coils on image quality].
AB  - OBJECTIVE: In magnetic resonance imaging (MRI) the image quality is considerably
      affected by the coil used, particularly when small structures are examined. The
      purpose of this study was to determine which coil provides the best scanning
      results for imaging of the temporomandibular joint (TMJ) of dogs and cats.
      MATERIAL AND METHODS: MRI investigations were performed using a standard human
      knee coil and an 8-cm-diameter surface coil with a low-field MRI-system (field
      strength 0.5 T). TMJs of two dogs and two cats were examined. The scan protocol
      consisted of T1-weighted spin echo (T1W/SE), T2-weighted turbo spin echo
      (T2W/TSE), a proton density-weighted sequence (PDW) (slice thickness: 3 mm each),
      and gradient echo sequences (slice thickness: 1-1.5 mm) in the sagittal plane.
      Three observers independently compared the features "contrast resolution", "bone
      structure", "spatial resolution", and "signal-to-noise ratio" (SNR) using a 5
      point scale. Investigators were blinded with respect to the coils used. RESULTS:
      Approximately 50% of the images obtained by the use of the surface coil were
      rated superior in comparison with the knee coil in terms of the features
      "contrast resolution", "bone structure", and "spatial resolution". In
      approximately 50% of the MRI-images no differences in the ratings were seen. With
      respect to the criterion "signal-to-noise ratio" 90% of the images acquired with
      the surface coil were rated better. In 5% of the images an identical quality was
      recorded. The surface coil proved to be superior both in dogs and cats.
      CONCLUSIONS AND CLINICAL RELEVANCE: Display quality of small structures of the
      TMJ is dependent on the spatial resolution of the MR images. Therefore, a
      dedicated coil and a small field of view (FOV) should be used. Results reveal
      that low-field MRI is able to display subtle anatomic structures of the TMJ in
      dogs and cats. In principle, the results can be transmitted to other MRI-systems.
      However, to generate valid scan protocols it is necessary to adapt scan
      parameters and coil selection specifically.

PMID- 22143587
TI  - Intercat aggression - general considerations, prevention and treatment.
AB  - Although cats are a social species and capable of living together in groups of
      several cats, intercat aggression is a common behavioral problem. Intercat
      aggression can be classified as status-related, fear- related, play-related,
      redirected and can also be due to the addition of a new cat to an existing group.
      Socialization of kittens, choice of the right cat for a multicat household, and
      the gradual introduction of a new cat to the household can help to prevent
      intercat aggression. Treatment of intercat aggression should combine behavior
      modification, management and - if necessary - medication.

PMID- 22143586
TI  - [Pilot study on the use of diode laser therapy for treatment of dermatitis in koi
      carp (Cyprinus carpio)].
AB  - OBJECTIVE: Therapy of dermatitis in koi using a diode laser technique. MATERIAL
      AND METHODS: A diode laser with a wavelength of 980 nm and an energy density of 9
      J/cm(2) was used to treat defined skin alterations in ten koi carp. The clinical
      situation after repeated laser application was recorded. In addition, the diode
      laser was used for surgical removal of proliferative skin alterations caused by
      Dermocystidium sp. in two koi ponds. RESULTS: An improvement of the clinical
      situation following laser therapy was seen in nine of the ten koi carp. Complete
      healing of the wound area occurred in four carp. A pronounced healing process was
      observed in four patients and a low healing tendency in one fish. Healing of the
      skin lesions following removal of the alterations caused by Dermocystidium sp.
      was unproblematic in one pond, whereas in the other collection a repeated
      treatment was necessary due to relapse of the alterations. CONCLUSIONS AND
      CLINICAL RELEVANCE: Diode laser therapy for treatment of dermatitis in koi is a
      promising technique. An expedited wound healing process was seen in wound areas
      that were present for long periods and resistant to previous therapy attempts,
      including antibiotics. Wound healing was undisturbed following surgical use of
      the laser technique for the removal of skin proliferations. Therefore, the diode
      laser technique can be recommended for the treatment of dermatitis in koi,
      especially in cases of unsuccessful treatment using anti-infective drugs, and for
      the treatment of Dermocystidium infections.

PMID- 22143588
TI  - [Multiple epiphyseal dysplasia in a Jack Russell Terrier].

PMID- 22143589
TI  - [Chocolate intoxication in a dog].

PMID- 22143590
TI  - Lissencephaly and microencephaly combined with hypoplasia of corpus callosum and
      cerebellum in a domestic cat.

PMID- 22143591
TI  - [Strategies for treating canine periodontal disease].

PMID- 22143593
TI  - Trends in socio-economic inequalities in female mortality, 2001-08. Intercensal
      estimates for England and Wales.
AB  - BACKGROUND: This article presents estimates of annual mortality rates for women
      of working age by the National Statistics Socio-economic Classification (NS-SEC)
      for the period 2001 to 2008. Until recently, it was possible to produce such
      mortality rates only at the time of the decennial census when populations are
      enumerated by occupation and NS-SEC. In 2010, ONS published annual intercensal
      male mortality rates using the Labour Force Survey (LFS) to provide population
      estimates by age and NS-SEC. This article produces the corresponding estimates
      for women aged 25 to 59. METHODS: The LFS was used to estimate female populations
      by age and NS-SEC for each year between 2001 and 2008. Numbers of deaths were
      obtained from death registrations. For both deaths and populations, the combined
      method of NS-SEC classification was used, whereby the most advantaged of a
      married woman's and her husband's NS-SEC was used to assign the woman to an NS
      SEC class. Single women were classified according to their own NS-SEC. Age
      standardised mortality rates were derived for each NS-SEC class by year and a
      number of measures of inequality estimated for each year so that any trends could
      be identified. RESULTS: While overall mortality rates for women declined over the
      period, this was not true for all NS-SEC classes. Managerial and professional
      occupations and Routine occupations experienced a statistically significant
      decline in mortality rate over the period. There was no clear trend for the other
      classes. Absolute measures of inequality showed no clear trend over the period,
      but relative inequalities tended to increase. Routine occupations had the
      greatest decline in mortality rate over the period of approximately five deaths
      per 100,000 per annum. CONCLUSIONS: Socio-economic inequalities in the mortality
      rates of women appeared to increase between 2001 and 2008. However, the results
      for women were not as clear as for men with four out of the seven analytic NS-SEC
      classes not having a statistically significant downward trend in mortality. The
      degree of annual volatility in the measures suggests that at the current low
      levels of mortality of working age women, the LFS could not be used to provide
      population denominators below the national level. Possibly, three-year moving
      averages would be better trend indicators, but this would reduce the timeliness
      of the data to some extent.

PMID- 22143594
TI  - The effect of lengthening life expectancy on future pension and long-term care
      expenditure in England, 2007 to 2032.
AB  - BACKGROUND: The aim of this analysis is to examine the effect of different
      assumptions about future trends in life expectancy (LE) on the sustainability of
      the pensions and long-term care (LTC) systems. The context is the continuing
      debate in England about the reform of state pensions and the reform of the system
      for financing care and support. METHODS: Macro and micro simulation models are
      used to make projections of future public expenditure on LTC services for older
      people and on state pensions and related benefits, making alternative assumptions
      on increases in future LE. The projections cover the period 2007 to 2032 and
      relate to England. RESULTS: Results are presented for a base case and for
      specified variants to the base case. The base case assumes that the number of
      older people by age and gender rises in line with the Office for National
      Statistics' principal 2006-based population projection for England. It also
      assumes no change in disability rates, no changes in patterns of care, no changes
      in policy and rises in unit care costs and real average earnings by 2 per cent
      per year. Under these assumptions public expenditure on pensions and related
      benefits is projected to rise from 4.7 per cent of Gross Domestic Product (GDP)
      in 2007 to 6.2 per cent of GDP in 2032 and public expenditure on LTC from 0.9 per
      cent of GDP in 2007 to 1.6 per cent of GDP in 2032. Under a very high LE variant
      to the GAD principal projection, however, public expenditure on pensions and
      related benefits is projected to reach 6.8 per cent of GDP in 2032 and public
      expenditure on LTC 1.7 per cent of GDP in 2032. CONCLUSIONS: Policymakers
      developing reform proposals need to recognise that, since future LE is inevitably
      uncertain and since variant assumptions about future LE significantly affect
      expenditure projections, there is a degree of uncertainty about the likely impact
      of demographic pressures on future public expenditure on pensions and LTC.

PMID- 22143597
TI  - Application of adapted tango as therapeutic intervention for patients with
      chronic stroke.
AB  - BACKGROUND AND PURPOSE: Dance has demonstrated beneficial effects on mobility in
      older individuals with movement disorders; yet, effects of partnered dance remain
      unexamined in individuals with chronic stroke. The purpose of this study was to
      describe the effects of adapted tango classes on balance, mobility, gait,
      endurance, dual-task ability, quality of life (QOL), and enjoyment in an older
      individual with chronic stroke and visual impairment. CASE DESCRIPTION: D.L. was
      a 73-year-old African American man, 13 years poststroke with spastic hemiplegia,
      visual impairment, and multiple comorbidities. INTERVENTION: D.L. attended 20 1?
      hour tango classes adapted for older individuals with sensory and motor
      impairments over 11 weeks. OUTCOMES: Measures of balance, mobility, gait,
      endurance, dual-task ability, and QOL were evaluated before and after the
      intervention and at 1-month follow-up. D.L. improved on the Berg Balance Scale,
      30-s chair stand, Timed Up and Go (single, manual, and cognitive conditions), 6
      minute walk test, and backward gait speed. Not all measures improved: balance
      confidence decreased, and there was no change in forward and fast gait speed or
      QOL, as measured by the short form-12 and the visual function questionnaire-25.
      Some gains were maintained at one-month follow-up. D.L. reported enjoying the
      classes, noted improvement in physical well-being, and wanted to continue the
      program. DISCUSSION: Thirty hours of adapted tango lessons improved balance,
      mobility, endurance, and dual-task ability in a participant with chronic stroke.
      The participant enjoyed the classes, was adherent, and wished to continue. This
      is the first reported use of adapted tango dance as rehabilitation for an
      individual with chronic stroke and low vision.

PMID- 22143600
TI  - 'We are still challenged to be dissatisfied'.

PMID- 22143599
TI  - Visualizing and quantifying acute inflammation using ICAM-1 specific
      nanoparticles and MRI quantitative susceptibility mapping.
AB  - As intense and prolonged inflammation correlates with the progression of various
      inflammatory diseases, locating specific regions of the body with dysregulated
      levels of inflammation could provide crucial information for effective medical
      diagnosis and treatment. In this study, we demonstrate high resolution
      spatiotemporal imaging of inflammation in mice treated with systemic injection of
      lipopolysaccharides (LPS) to mimic systemic inflammatory response or sepsis.
      Diagnosis of organ-level inflammation was achieved by magnetic resonance imaging
      (MRI) of inflammation-sensitive superparamagnetic iron oxide (SPIO)-based
      nanomicelle termed leukocyte-mimetic nanoparticle (LMN), designed to
      preferentially localize to cells with inflammation-induced overexpression of
      intercellular adhesion molecule (ICAM)-1. Using a novel MRI quantitative
      susceptibility mapping (QSM) technique for non-invasive quantification of SPIO
      nanoparticles, we observed greater accumulation of LMN in the liver, specific to
      ICAM-1 induction due to LPS-induced inflammation. However, the accumulation of
      nanoparticles into the spleen appeared to be due to an ICAM-1 independent,
      phagocytic activity, resulting in higher levels of both LMN and control
      nanoparticles in the spleen of LPS-treated than untreated mice. Overall, the
      amounts of nanoparticles in liver and spleen estimated by QSM were in a good
      agreement with the values directly measured by radioactivity, presenting an idea
      that spatiotemporal mapping of LMN by MRI QSM may provide a reliable, rapid, non
      invasive method for identifying organ-specific inflammation not offered by
      existing diagnostic techniques.

PMID- 22143598
TI  - Nanofabrication for the analysis and manipulation of membranes.
AB  - Recent advancements and applications of nanofabrication have enabled the
      characterization and control of biological membranes at submicron scales. This
      review focuses on the application of nanofabrication towards the nanoscale
      observing, patterning, sorting, and concentrating membrane components. Membranes
      on living cells are a necessary component of many fundamental cellular processes
      that naturally incorporate nanoscale rearrangement of the membrane lipids and
      proteins. Nanofabrication has advanced these understandings, for example, by
      providing 30 nm resolution of membrane proteins with metal-enhanced fluorescence
      at the tip of a scanning probe on fixed cells. Naturally diffusing single
      molecules at high concentrations on live cells have been observed at 60 nm
      resolution by confining the fluorescence excitation light through nanoscale
      metallic apertures. The lateral reorganization on the plasma membrane during
      membrane-mediated signaling processes has been examined in response to nanoscale
      variations in the patterning and mobility of the signal-triggering molecules.
      Further, membrane components have been separated, concentrated, and extracted
      through on-chip electrophoretic and microfluidic methods. Nanofabrication
      provides numerous methods for examining and manipulating membranes for both
      greater understandings of membrane processes as well as for the application of
      membranes to other biophysical methods.

PMID- 22143601
TI  - Cardiovascular health in the Americas: facts, priorities and the UN high-level
      meeting on non-communicable diseases.
AB  - Population aging, smoking, unhealthy diet and physical inactivity, in the context
      of globalization and unregulated urbanization, explain the high prevalences of
      hypertension, hypercholesterolemia and diabetes in the Americas, making
      cardiovascular diseases the main cause of death. Moreover, cardiovascular
      diseases and their risk factors disproportionately affect the poorest people,
      obstructing antipoverty efforts and further deepening health and other
      inequities. The global crisis of chronic non-communicable diseases has reached
      such proportions that the UN General Assembly called a high-level meeting in
      September 2011 to address the issue as one of human development, aiming to
      stimulate political commitment to a concerted global effort to stem the pandemic.
      In reference to the Americas, this article reviews the burden of cardiovascular
      diseases and describes priorities for strategies and action in the region and
      their relation to the results of the UN meeting.

PMID- 22143602
TI  - New survey results enhance Cuba's NCD surveillance: Mariano Bonet MD, Director,
      National Hygiene, Epidemiology and Microbiology Institute.

PMID- 22143603
TI  - Chronic kidney disease and associated risk factors in the Bajo Lempa region of El
      Salvador: Nefrolempa study, 2009.
AB  - INTRODUCTION: In El Salvador, end-stage renal disease is the leading cause of
      hospital deaths in adults, the second cause of death in men and the fifth leading
      cause of death in adults of both sexes in the general population. OBJECTIVE:
      Identify risk factors for chronic kidney disease and urinary markers of renal and
      vascular damage, measure kidney function and characterize prevalence of chronic
      kidney disease in persons aged >=18 years in the Bajo Lempa region of El
      Salvador. METHODS: A cross-sectional analytical epidemiological study was carried
      out using active screening for chronic kidney disease and associated risk factors
      in individuals aged >=18 years in the Bajo Lempa Region, a rural, coastal area in
      El Salvador. Door-to-door visits and clinical examinations were conducted.
      Epidemiological and clinical data were collected including: family and personal
      clinical history of disease; biological, behavioral, social and environmental
      risk factors; physical measurements; urinalysis for markers of renal and vascular
      damage; and blood tests (serum creatinine, serum glucose, lipid profile).
      Glomerular filtration rate was calculated using the Modification of Diet in Renal
      Disease formula. Chronic kidney disease case confirmation was done three months
      later. Multiple logistic regression was used for data analysis. RESULTS: A total
      of 375 families and 775 individuals (343 men, 432 women) were studied-88.3% of
      the total resident population in the region. Elevated prevalence of risk factors
      was observed: diabetes mellitus, 10.3%; hypertension,16.9%; family history of
      chronic kidney disease, 21.6%; dyslipidemias, 63.1%; overweight, 34%; obesity,
      22.4%; metabolic syndrome, 28.8%; use of non-steroidal anti-inflammatory drugs,
      74.8%; infectious diseases, 86.9%; agricultural occupation, 40.6% (80.6% in men);
      and contact with agrochemicals, 50.3% (82.5% in men). Prevalence renal damage
      markers was 15.8% (greater in men): microalbuminuria 6.3%; proteinuria 5.7%;
      hematuria 3.5%; proteinuria-hematuria 0.3%. Proteinuria of <1 g/L predominated.
      Prevalence of chronic kidney disease was 17.9% (25.7% in men; 11.8% in women).
      Distribution by stages: stage 1, 4.6%; stage 2, 3.5%; stage 3, 6.2%; stage 4,
      3.0%; stage 5, 0.6%. In patients with chronic kidney disease, most common was non
      diabetic chronic kidney disease (86.3%), followed by chronic kidney disease
      associated with neither diabetes nor hypertension (54.7%). Prevalence of chronic
      renal failure was 9.8% (17% in men; 4.1% in women). Multiple logistic regression
      showed significant association with increasing age, male sex, hypertension and
      family history of chronic kidney disease. CONCLUSIONS: Elevated prevalence of
      chronic kidney disease, chronic renal failure and risk factors was found,
      compared to international reports. Most common was chronic kidney disease of
      unknown cause, associated with neither diabetes nor hypertension. Associations
      were found with age, male sex, hypertension and family history of chronic kidney
      disease, with decline in kidney function beginning at early ages. Male farmers
      have a dual burden of non traditional (occupational, toxic environmental) and
      traditional (vascular) risk factors that could act in synergy, contributing to
      kidney damage.

PMID- 22143604
TI  - Acute myocardial infarction incidence, mortality and case fatality in Santa
      Clara, Cuba, 2007-2008.
AB  - INTRODUCTION: Information on acute myocardial infarction incidence and mortality
      is essential for determining the efficacy of the health system's cardiovascular
      disease prevention activities; however, in Cuba, sufficient data related to acute
      myocardial infarction are lacking, particularly at the local level. OBJECTIVE:
      Describe acute myocardial infarction incidence, mortality and case fatality rates
      from January 2007 through December 2008 in persons aged 45-74 in the municipality
      of Santa Clara, Villa Clara Province, Cuba. METHODS: A retrospective descriptive
      study was conducted. The World Health Organization MONItoring Trends and
      Determinants in CArdiovascular Disease Project (MONICA) methodology was used, but
      only in part, since out-of-hospital case fatalities were not investigated,
      resulting in insufficient data for such cases. Cases of acute myocardial
      infarction covered under MONICA definition 1 were included (non-fatal definite,
      fatal definite, fatal possible, and unclassifiable deaths). Hospitalized patients
      were followed for 28 days. Incidence, mortality and case fatality rates in the
      population were calculated by age group (45-54, 55-64 and 65-74 years) and sex.
      Age-standardized incidence and mortality rates were calculated using the direct
      method, with the world population as a reference. RESULTS: A total of 482 cases
      of acute myocardial infarction were registered. The percentage of cases of non
      fatal definite, fatal definite, fatal possible and fatal with insufficient data
      were 32%, 18.3%, 26.3% and 13.9% respectively. The cumulative age-standardized
      incidence per 100,000 population was 433 (95% CI 365-501) in men and 195 (95% CI
      152-237) in women, while mortality per 100,000 population was 242 (95% CI 192
      292) in men and 120 (95% CI 87-153) in women. Case fatality was 56.4% in men and
      62.6% in women. Most fatal cases (65.6%) occurred out of hospital, a trend that
      was more marked in men (73.9%) than in women (51%). CONCLUSIONS: Case fatality
      from acute myocardial infarction in Santa Clara residents was high, especially in
      women. Two thirds of fatalities occurred out of hospital, a higher proportion of
      these deaths in men. It is recommended that the AMI registry be completed by
      investigating out-of-hospital case fatalities with insufficient data; expanding
      it to include the 35-44 age group; and that the supply of cardiac marker enzyme
      immunoassay test kits in Santa Clara be stabilized.

PMID- 22143605
TI  - Dementia and other chronic diseases in older adults in Havana and Matanzas: the
      10/66 study in Cuba.
AB  - INTRODUCTION: Chronic non-communicable diseases are the leading cause of death
      worldwide, except in Sub-Saharan Africa. Nonetheless, one of these conditions,
      dementia, is the major contributor to disability-adjusted life years in people
      aged >=60 years. Few epidemiological studies exist of the prevalence and impact
      of dementia and selected chronic diseases in older adults in Latin America.
      OBJECTIVE: Describe prevalence of dementia, other chronic vascular diseases and
      cardiovascular risk factors, as well as resulting disabilities and care needs
      generated in adults aged >=65 years in Havana City and Matanzas provinces, Cuba.
      METHODS: The 10/66 study is a prospective longitudinal study involving a cohort
      of 3015 adults aged >=65 years in municipalities of Havana City and Matanzas
      provinces, divided into two phases: a cross-sectional door-to-door study
      conducted in 2003-2006, and a follow-up and assessment phase in 2007-2010. This
      article reports findings from the first phase. Hypertension diagnosis was based
      on criteria from the International Society for Hypertension; diabetes mellitus on
      American Diabetes Association criteria; stroke according to WHO definitions; and
      dementia according to criteria of the American Psychiatric Society's Diagnostic
      and Statistical Manual of Mental Disorders DSM-IV and the 10/66 International
      Dementia Research Group. Ischemic heart disease was defined by self-report of
      previous physician diagnosis. Study variables included age, sex, educational
      level, substance use (alcohol, tobacco) and dietary habits. A structured physical
      and neurological exam, including blood pressure measurement, was performed on all
      participants. Laboratory tests included complete blood count, fasting blood
      glucose, total cholesterol and lipoprotein fractions, triglycerides and
      apolipoprotein E genotype. Prevalence and standardized morbidity ratios (crude
      and adjusted) were calculated for chronic diseases studied with 95% confidence
      intervals, using a Poisson regression model and indirect standardization.
      RESULTS: The study assessed 2944 older adults (response rate 97.6%) and found
      high prevalence of vascular risk factors and of chronic non-communicable
      diseases: hypertension 73.0% (95% CI 71.4-74.7), diabetes mellitus 24.8% (95% CI
      22.9-26.5), ischemic heart disease 14.1% (95% CI 12.9-15.4), dementia 10.8% (95%
      CI 9.7-12.0) and stroke 7.8% (95% CI 6.9-8.8). The majority of participants (85%)
      had more than one cardiovascular risk factor. The main cause of disability and
      dependency in the study population was dementia. CONCLUSION: The high prevalence
      of chronic diseases observed in the elderly--with the consequent morbidity,
      disability and dependency--highlights the need for prevention, early diagnosis
      and risk factor control, particularly given the demographic and epidemiologic
      transition faced by Cuba and other developing countries.

PMID- 22143606
TI  - Tobacco and alcohol use in Cuban women.
AB  - INTRODUCTION: Tobacco and alcohol are currently the most widely consumed legal
      psychoactive substances in the world. They represent a heavy burden for health
      and society in almost all populations. Increasing consumption of both substances
      is a trend observed in women. OBJECTIVE: Describe the profile of women aged >=15
      years residing in urban areas of Cuba with respect to tobacco and alcohol
      consumption. METHOD: Basic information on tobacco and alcohol consumption by
      Cubans aged >=15 years in urban areas was obtained from the Second National
      Survey on Risk Factors and Chronic Diseases (2001), a national descriptive cross
      sectional study, the objective of which was to determine the frequency and
      epidemiological characteristics of the urban population's main chronic disease
      risk factors. Sampling design was complex stratified multi-stage cluster. Of a
      sample of 23,743 individuals, 22,851 were surveyed, representative of 6.8 million
      Cubans. A questionnaire and structured interview were used. Variables were
      tobacco and alcohol use, as well as sociodemographic factors: sex, age,
      educational level, skin color, marital status, type of full-time employment and
      perceived economic situation. Prevalence, with 95% confidence intervals, and
      male:female prevalence ratios were estimated. RESULTS: Women who smoked were
      predominantly aged 40-59 years; had completed less than university education; of
      black skin color; divorced; laborers, service workers or managers, and with a
      perceived economic situation as very poor. Women who consumed alcohol were
      predominantly aged 15-59 years, had at least middle school education, of mestizo
      or black skin color, of marital status other than widowed; there was no typical
      profile for occupation or perceived economic situation. Women who were both
      smokers and alcohol consumers were predominantly 20-59 years, of black or mestizo
      skin color, of marital status other than widowed; with no typical profile for
      educational level, occupation or perceived economic situation. CONCLUSIONS: The
      first nationwide socioeconomic profile of Cuban women using tobacco, alcohol or
      both constitutes a baseline for comparison to results of a new national study now
      under way, permitting evaluation of trends over time and effectiveness of
      prevention and control efforts.

PMID- 22143607
TI  - Role of herpesvirus as a cause of mononucleosis-like and febrile syndromes in
      Cuba, 2006-2009.
AB  - INTRODUCTION: Herpesvirus infections are prevalent worldwide, but most run their
      course asymptomatically. Clinical presentations in symptomatic cases vary widely
      and include febrile and mononucleosis-like syndromes. In immunocompromised
      patients, herpetic infection can be lethal and routine laboratory tests are of
      little use. Use of novel techniques may provide important improvements in
      diagnosis and treatment of these patients. OBJECTIVE: Investigate association
      between different herpesviruses and the etiology of mononucleosis and febrile
      syndromes in Cuban immunocompetent and immunocompromised patients. METHODS: The
      study used multiplex nested polymerase chain reaction, enabling simultaneous
      detection of six herpesviruses--cytomegalovirus, herpes simplex (1 and 2),
      Epstein-Barr, varicella-zoster and human herpesvirus 6--to study 1157 samples
      (770 urine and 387 serum samples) from 1140 patients with mononucleosis-like
      syndrome or febrile syndrome, classified according to history of
      immunosuppressive disease. Samples were analyzed at the Laboratory for Sexually
      Transmitted Diseases (Virology) of the Pedro Kouri Tropical Medicine Institute
      from January 2006 through December 2009. SPSS statistical package was used and
      incidence rates calculated. RESULTS: Of samples studied, 20.1% were positive for
      some herpesvirus. Higher risk of developing active herpesvirus infections was
      detected in samples from immunocompromised patients with febrile syndrome
      compared to those of immunocompetent ones (OR 2.02, CI 1.20-3.42, p=0.007).
      Cytomegalovirus was the most frequently found herpesvirus in both mononucleosis
      like syndrome (60.4%) and febrile syndrome (63.6%) and in both children (69.2%)
      and adults (55.2%), followed by Epstein-Barr virus. Cytomegalovirus was detected
      in 68.9% of positive urine samples and in just 47.2% of serum samples.
      CONCLUSIONS: This is the first Cuban study demonstrating the pathogenic role of
      herpesviruses, particularly cytomegalovirus, in patients with febrile or
      mononucleosis-like syndrome, in both immunocompetent and immunocompromised
      patients. Results highlight the importance of including molecular diagnosis of
      the herpesvirus family in investigating mononucleosis and febrile syndromes of
      unknown etiology and demonstrate that etiologic diagnosis would not have been
      feasible in many cases without the use of this diagnostic tool.

PMID- 22143608
TI  - Alcohol: friend or foe?
AB  - Popular belief has it that alcohol, particularly red wine, protects against
      atherosclerosis and associated cardio- and cerebrovascular conditions. That
      presumption motivates this paper, which describes the mechanisms underlying the J
      shaped risk curve for alcohol use, with benefits for vascular disease risk at low
      consumption levels and harmful effects--both directly on the user and indirectly
      on the bystander--at higher levels. The importance of further exploring alcohol
      use in patients with cardiovascular risk factors and of intervening to modify non
      social use of alcohol to prevent serious adverse health consequences is also
      addressed.

PMID- 22143609
TI  - Women & smoking: becoming part of the solution.

PMID- 22143610
TI  - Radicals in transition metal catalyzed reactions? transition metal catalyzed
      radical reactions? - a fruitful interplay anyway: part 2. Radical catalysis by
      group 8 and 9 elements.
AB  - This review summarizes the current status of transition metal catalyzed reactions
      involving radical intermediates in organic chemistry. This part focuses on
      radical-based methods catalyzed by group 8 and group 9 metal complexes. Reductive
      and redox-neutral coupling methods catalyzed by low-valent metal complexes as
      well as catalytic oxidative C-C bond formations are reviewed.

PMID- 22143611
TI  - Radicals in transition metal catalyzed reactions? transition metal catalyzed
      radical reactions?: a fruitful interplay anyway: part 3: catalysis by group 10
      and 11 elements and bimetallic catalysis.
AB  - This review summarizes the current status of transition metal catalyzed reactions
      involving radical intermediates in organic chemistry. This part focuses on
      radical-based methods catalyzed by group 10 and group 11 metal complexes.
      Reductive and redox-neutral C-C bond formations catalyzed by low-valent metal
      complexes as well as catalytic oxidative methods are reviewed. Catalytic
      processes which rely on the combination of two metal complexes are also covered.

PMID- 22143612
TI  - Guillain-Barre syndrome associated with normal or exaggerated tendon reflexes.
AB  - Areflexia is part one of the clinical criteria required to make a diagnosis of
      Guillain-Barre syndrome (GBS). The diagnostic criteria were stringently developed
      to exclude non-GBS cases but there have been reports of patients with GBS
      following Campylobacter jejuni enteritis with normal and exaggerated deep tendon
      reflexes (DTRs). The aim of this study is to expand the existing diagnostic
      criteria to preserved DTRs. From the cohort of patients referred for anti
      ganglioside antibody testing from hospitals throughout Japan, 48 GBS patients
      presented with preserved DTR at admission. Thirty-two patients had normal or
      exaggerated DTR throughout the course of illness whereas in 16 patients the DTR
      became absent or diminished during the course of the illness. IgG antibodies
      against GM1, GM1b, GD1a, or GalNAc-GD1a were frequently present in either group
      (84 vs. 94%), suggesting a close relationship between the two groups. We then
      investigated the clinical and laboratory findings of 213 GBS patients from three
      hospital cohorts. In 23 patients, eight presented with normal tendon reflexes
      throughout the clinical course of the illness. Twelve showed hyperreflexia, with
      at least one of the jerks experienced even at nadir, and exaggerated reflexes
      returning to normal at recovery. The other three had hyperreflexia throughout the
      disease course. Compared to 190 GBS patients with reduced or absent DTR, the 23
      DTR-preserved patients more frequently presented with pure motor limb weakness
      (87 vs. 47%, p = 0.00026), could walk 5 m independently at the nadir (70 vs. 33%,
      p = 0.0012), more frequently had antibodies against GM1, GM1b, GD1a, or GalNAc
      GD1a (74 vs. 47%, p = 0.014) and were more commonly diagnosed with acute motor
      axonal neuropathy (65 vs. 34%, p = 0.0075) than with acute inflammatory
      demyelinating polyneuropathy (13 vs. 43%, p = 0.0011). This study demonstrated
      that DTRs could be normal or hyperexcitable during the entire clinical course in
      approximately 10% of GBS patients. This possibility should be added in the
      diagnostic criteria for GBS to avoid delays in diagnosis and effective treatment
      to these patients.

PMID- 22143613
TI  - Failure of long-term subthalamic nucleus stimulation corrected by additional
      pallidal stimulation in a patient with Parkinson's disease.

PMID- 22143614
TI  - Deficient sustained attention to response task and P300 characteristics in early
      Huntington's disease.
AB  - Evidence for the extent and nature of attentional impairment in premanifest and
      manifest Huntington's disease (HD) is inconsistent. Understanding such
      impairments may help to better understand early functional changes in HD and
      could have consequences concerning care for HD patients. We investigated
      attentional control in both early and premanifest HD. We studied 17 early HD
      subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years),
      and 15 healthy controls (mean age: 51 years), using the sustained attention to
      response task (SART), a simple Go/No-go test reflecting attentional and
      inhibitory processes through reaction time (RT) and error rates. Simultaneously
      recorded EEG yielded P300 amplitudes and latencies. The early HD group made more
      Go errors (p < 0.001) and reacted slower (p < 0.005) than the other groups. The
      RT pattern during the SART was remarkably different for early HD subjects
      compared to the other two groups (p < 0.005), apparent as significant post-error
      slowing. P300 data showed that for early HD the No-go amplitude was lower than
      for the other two groups (p < 0.05). Subjects with early HD showed a reduced
      capacity to effectively control attention. They proved unable to resume the task
      directly after having made an error, and need more time to return to pre-error
      performance levels. No attentional control deficits were found for the
      premanifest HD group.

PMID- 22143616
TI  - The nuclear receptors NUR77, NURR1 and NOR1 in obesity and during fat loss.
AB  - BACKGROUND: Adipose tissue is critical for systemic metabolic health. Identifying
      key factors regulating adipose tissue function is a research priority. The NR4A
      subfamily of nuclear receptors (NRs) (NR4A1/NUR77, NR4A2/NURR1 and NR4A3/NOR1)
      has emerged as important proteins in different disease states and in the
      regulation of metabolic tissues, particularly in liver and muscle. However, the
      expression of the NR4A members in human adipose tissue has not previously been
      described, and their target genes are largely unknown. OBJECTIVE: To determine
      whether the NR4As are differentially expressed in human adipose tissue in
      obesity, and identify potential NR4A target genes. DESIGN: Prospective analysis
      of s.c. adipose tissue before and 1 year after fat loss, and during in vitro
      differentiation of primary human preadipocytes. Case-control comparison of
      omental (OM) adipose tissue. SUBJECTS: A total of 13 extremely obese patients
      undergoing biliopancreatic diversion with duodenal switch for fat loss, 12
      extremely obese patients undergoing laparoscopic sleeve gastrectomy and 37 lean
      individuals undergoing hernia repair or laparotomy were included in the study.
      Measurements were done by quantitative PCR gene expression analysis of the NR4A
      members and in silico promoter analysis based on microarray data. RESULTS: There
      was a strong upregulation of the NR4As in extreme obesity and normalization after
      fat loss. The NR4As were expressed at the highest level in stromal-vascular
      fraction compared with adipocytes, but were downregulated in both fractions after
      fat loss. Their expression levels were also significantly higher in OM compared
      with s.c. adipocytes in obesity. The NR4As were downregulated during
      differentiation of primary human preadipocytes. Moreover, the NR4As were strongly
      induced within 30 min of tissue incubation. Finally, promoter analysis revealed
      potential NR4A target genes involved in stress response, immune response,
      development and other functions. Our data show altered adipose tissue expression
      of the NR4As in obesity, suggesting that these stress responsive nuclear
      receptors may modulate pathogenic potential in humans.

PMID- 22143618
TI  - The impact of obesity on secretion of adiponectin multimeric isoforms differs in
      visceral and subcutaneous adipose tissue.
AB  - OBJECTIVE: Hypoadiponectinemia observed in obesity is associated with insulin
      resistance, diabetes and atherosclerosis. The aim of the present study was to
      investigate secretion of adiponectin and its multimeric isoforms by explants
      derived from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)
      in obese and non-obese subjects. DESIGN: Paired samples of SAT and VAT and blood
      samples were obtained from 23 subjects (10 non-obese and 13 obese) undergoing
      elective abdominal surgery. Total adiponectin quantities and adiponectin isoforms
      were measured in conditioned media of explants derived from SAT and VAT using
      enzyme-linked immunosorbent assay and non-denaturing western blot, respectively.
      RESULTS: Total adiponectin plasma levels were lower in obese than in non-obese
      subjects (P<0.05). Secretion of total adiponectin in adipose tissue (AT) explants
      was lower in obese than in non-obese subjects in SAT (P<0.05) but not in VAT. In
      both, SAT and VAT, the most abundant isoform released into conditioned media was
      the high-molecular weight (HMW) form. Its relative proportion in relation to
      total adiponectin was higher in conditioned media of explants from both fat
      depots when compared with plasma (P<0.001). The proportion of secreted HMW vs
      total adiponectin was higher in VAT than in SAT explants in the group of non
      obese individuals (49.3+/-3.1% in VAT vs 40.6+/-2.8% in SAT; P<0.01), whereas no
      difference between the two depots was found in obese subjects (46.2+/-3.0 % in
      VAT vs 46.0+/-2.4 % in SAT). CONCLUSION: Obesity is associated with the decrease
      of total adiponectin secretion in SAT. The profile of adiponectin isoforms
      secreted by SAT and VAT explants differs from that in plasma. Secretion of total
      adiponectin and HMW isoform of adiponectin are different in obese and non-obese
      subjects in relation to AT depot.

PMID- 22143617
TI  - Food images engage subliminal motivation to seek food.
AB  - Human eating behaviour is motivated and shaped by a complex interaction of
      internal drives such as hunger, external influences such as environmental cues
      and the sensory properties of food itself. Thus, as is demonstrated by the
      example of sensory-specific satiety (SSS), hunger may be reduced but particular
      foods (for example, desserts) retain their attraction and their ability to prompt
      consumption. In considering consumption, and overconsumption, it is therefore
      important to understand the interaction between internal and external drives to
      eat. Using grip force as a measure of motivation, we examined this interaction
      using an SSS manipulation. Critically, we sought to determine whether food
      stimuli would exert their influence even when they were subliminally presented
      (and thus not accessible to consciousness), and whether this unconscious
      influence would be flexibly updated in response to changes in food reward value
      with satiety. Demonstrating that the SSS effect remains when external stimuli are
      not consciously perceived, our data highlight the importance of even the most
      subtle, fleeting and even subliminal external events in shaping our motivation
      towards food.

PMID- 22143619
TI  - The impact of cash transfers to poor women in Colombia on BMI and obesity:
      prospective cohort study.
AB  - INTRODUCTION: Prevalence of obesity is rising in Latin America and increasingly
      affecting socially disadvantaged groups, particularly women. Conditional cash
      transfers are recently established welfare interventions in the region. One,
      Familias en Accion, transfers ~20% of average monthly income to women in
      Colombia's poorest families. Previous work has found that families buy more food
      as a result. We tested the hypothesis that participation in Familias would be
      associated with increasing body mass index (BMI) in participating women. METHODS:
      Women from participating areas and control areas (matched on environmental and
      socioeconomic criteria) were surveyed in 2002 and 2006. Pregnant, breast-feeding
      or women aged <18 or with BMI <18.5 kg m(-2) were excluded. The sample comprises
      835 women from control and 1238 from treatment areas. Because some treatment
      areas started Familias shortly before baseline data collection, a dummy variable
      was created that identified exposure independent of time point or area. Follow-up
      was 61.5%. BMI was measured by trained personnel using standardized techniques.
      Overweight was defined as BMI >= 25 kg m(-2) and obesity as >= 30 kg m(-2). The
      effect of Familias was estimated using linear regression (or logistic regression
      for dichotomous outcomes) in a double-difference technique, controlling for
      several individual, household and area characteristics, including parity and
      baseline BMI, using robust standard-errors clustered at area-level in an
      intention-to-treat analysis. RESULTS: At baseline, women's mean age was 33.3
      years and mean BMI 25.3 kg m(-2); 12.3% women were obese. After adjustment,
      exposure to Familias was significantly associated with increased BMI (beta=0.25;
      95% confidence interval (CI) 0.03, 0.47; P=0.03). Age (beta=0.09; 95% CI 0.06,
      0.13; P<0.001) and household wealth (beta=0.78; 95% CI 0.41, 1.15; P<0.001) were
      also positively associated with BMI. Familias was also associated with increased
      odds of obesity (odds ratio (OR)=1.27; 95% CI 1.03, 1.57; P=0.03), as was age
      (OR=1.04; 95% CI 1.02, 1.06; P=0.001). CONCLUSION: Conditional cash transfers to
      poor women in Colombia are independently associated with increasing BMI and
      obesity risk. Although conditional cash transfers are generally regarded as
      popular and successful schemes, parallel interventions at individual, household
      and community level are needed to avoid unanticipated adverse outcomes.

PMID- 22143620
TI  - Hepatic left lobe volume is a sensitive index of metabolic improvement in obese
      women after gastric banding.
AB  - BACKGROUND: Nonalcoholic fatty liver disease is a common finding in obese
      subjects. Increasing evidence has been provided suggesting that it represents the
      hepatic component of the metabolic syndrome. OBJECTIVE: Aim of this longitudinal
      study was to evaluate the relationships between several anthropometric measures,
      including the hepatic left lobe volume (HLLV), and various indicators of the
      metabolic syndrome in a cohort of severely obese women before and after
      laparoscopic adjustable gastric banding (LAGB). STUDY DESIGN AND RESULTS: Seventy
      five obese women (mean age 45 +/- 10 years and body mass index (BMI) 42.5 +/- 4.8
      kg m(-2)) underwent LAGB and completed an average (+/- s.d.) post-surgical follow
      up of 24 +/- 6 months. Determination of HLLV, subcutaneous and intra-abdominal
      fat (IAF) was based on ultrasound. The principal component statistical analysis
      applied to pre-operative measurements, highlighted HLLV as a parameter that
      clustered with serum insulin, IAF, serum glucose and uric acid, along with
      triglycerides (TGs), alkaline phosphatase and high-density lipoprotein
      cholesterol. After LAGB, the average reduction of BMI was 23%, 12% for
      subcutaneous fat (SCF), 42% for HLLV and 40% for visceral fat. Among body weight,
      BMI, SCF, IAF and HLLV, reduction of the latter was an independent predictor of
      reduction of serum transaminases and gamma-Glutamyltransferase, glucose, insulin
      and TGs. CONCLUSIONS: In severely obese women: (i) HLLV is a sensitive indicator
      of ectopic fat deposition, clustering with parameters defining the metabolic
      syndrome; (ii) weight loss achieved by LAGB is associated with a reduction of
      liver volume as estimated by HLLV; (iii) among various anthropometric parameters
      measured, reduction of HLLV that follows LAGB represents the best single
      predictor of improvement of various cardiometabolic risk factors.

PMID- 22143621
TI  - Learning about the energy density of liquid and semi-solid foods.
AB  - BACKGROUND: People learn about a food's satiating capacity by exposure and
      consequently adjust their energy intake. OBJECTIVE: To investigate the effect of
      energy density and texture on subsequent energy intake adjustments during
      repeated consumption. DESIGN: In a randomized crossover design, participants
      (n=27, age: 21+/-2.4 years, body mass index: 22.2+/-1.6 kg m(-2)) repeatedly
      consumed highly novel foods that were either low-energy-dense (LE: 30 kcal per
      100 g) or high-energy-dense (HE: 130 kcal per 100 g), and either liquid or semi
      solid, resulting in four product conditions. In each condition, a fixed portion
      of test food was consumed nine times as an obligatory part of breakfast, lunch
      and dinner on 3 consecutive days. All meals continued with an ad libitum buffet;
      food items for evening consumption were provided and the intake (kcal per day)
      was measured. RESULTS: Buffet intake depended on energy density and day of
      consumption of the test foods (day*energy interaction: P=0.02); daily buffet
      intake increased from day 1 (1745+/-577 kcal) to day 3 (1979+/-567 kcal) in the
      LE conditions; intake did not change in the HE conditions (day 1: 1523+/-429
      kcal, day 3: 1589+/-424 kcal). Food texture did not affect the intake (P=0.56).
      CONCLUSIONS: Intake did depend on energy density of the test foods; participants
      increased their buffet intake over days in response to learning about the
      satiating capacity of the LE foods, but did not change buffet intake over days
      when repeatedly consuming a HE food as part of their meal. The adjustments in
      intake were made irrespective of the food texture.

PMID- 22143623
TI  - [Computed tomography imaging of the temporomandibular joint in dogs and cats.
      Effects of different scan parameters on image quality].
AB  - OBJECTIVE: Temporomandibular joints (TMJs) of dogs and cats were examined with
      multislice computed tomography (MSCT) using different technical scan parameters
      in order to investigate their impact on image quality. Another aspect was to
      analyze whether size differences of the TMJ affect the display of small joint
      structures. MATERIAL AND METHODS: The TMJs of two dogs and two cats were examined
      using MSCT. Scan parameters were varied including tube current, scan matrix,
      resolution mode, slice thickness, and reconstruction increment. Three observers
      being blinded with respect to the used scan parameters independently assessed the
      image quality in terms of "contrast resolution", "bone structure", "spatial
      resolution", "evaluation of the joint space", and "artefacts" according to a 4
      point scale. RESULTS: The criteria "spatial resolution" and "evaluation of the
      joint space" emphasize the influence of the size of the TMJ. The image quality of
      the TMJ of the dogs was evaluated superior (by 0.5 to 1.5 points higher graded)
      compared to the smaller ones of the cats. In terms of "spatial resolution" and
      "bone structure" the images of an ultra high resolution technique achieved a
      higher evaluation level (scoring one point superior) compared to the images
      created by a high resolution protocol. The tube current did not significantly
      influence the image quality in any of the pictures. CONCLUSIONS AND CLINICAL
      RELEVANCE: The display quality of small structures of the TMJ is dependent on the
      spatial resolution of the CT images. Therefore, a thin slice collimation, a small
      field of view, and a high resolution reconstruction matrix should be used. Under
      those aspects subtle alterations of bone structure of the TMJ can be reliably
      detected. The soft tissue structures of the TMJ can not be visualized with MSCT
      in small animals. In principle, the results can be applied to any other MSCT
      scanner. However, adjustments of the technical parameters may be still necessary.

PMID- 22143622
TI  - The effect of obesity on adverse outcomes and metabolism in pediatric burn
      patients.
AB  - HYPOTHESIS: Obesity influences metabolism and increases the incidence of clinical
      complications and worsens outcomes in pediatric burn patients. DESIGN:
      Retrospective, single-center study. SUBJECTS: In all, 592 severely burned
      pediatric patients who had burns covering more than 30% of the total body surface
      area and who were treated between 2001 and 2008 were enrolled in this study.
      Patients were divided into >=85th percentile (n=277) and normal (n=315) weight
      groups based on body mass index (BMI) percentiles. RESULTS: Patients stratified
      below (normal) and >=85th percentile had similar age, gender distribution and
      total burn size. No significant differences were detected in the incidence of
      sepsis (11% for obese vs 10% for normal), the incidence of multiple organ failure
      (MOF) (21% for obese and 16% for normal) or mortality (11% for obese vs 8% for
      normal). Compared with the normal group, the >=85th percentile group had low
      levels of constitutive proteins (alpha2macroglobulin and Apolipoprotein A1)
      (P<0.05 for both) as well as high levels of triglycerides and the acute-phase
      protein, C-reactive protein (P<0.05 for both) up to 60 days after injury.
      Patients >=85th percentile showed a significant higher loss of bone mineral
      density and lipolysis compared with normal individuals. Stepwise logistic
      regression analysis revealed that BMI had a positive predictive value towards the
      maximum DENVER2 score, an index of organ failure (P<0.001). CONCLUSIONS:
      BMI>=85th percentile altered the post-burn acute phase and catabolic response but
      did not increase the incidence of sepsis, MOF or mortality in pediatric burn
      patients. Our results suggest that impaired metabolism and an altered
      inflammatory response already exists in patients starting at the 85th percentile
      BMI.

PMID- 22143624
TI  - [Effects of a neuroleptic analgesia with acepromazine on the blood perfusion of
      the canine kidney. Examination using the sonographic recordable blood circulation
      parameters of resistance index and pulsatility index].
AB  - OBJECTIVE: Kidney failure after anaesthesia constitutes a serious clinical
      complication. A number of patients suffer from compensated kidney insufficiency,
      which may be transformed into an acute kidney insufficiency through additional
      stress, such as an operation and anaesthesia. The aim of the present study was to
      investigate the effects of a neurolept analgesia with acepromazine on
      sonographically accessible blood perfusion parameters. MATERIAL AND METHODS:
      Following anaesthesia with acepromazine/l-methadone (0.1 mg/kg BW acepromazine,
      0.5 mg/kg BW l-methadone) a sonographic examination of the left kidney was
      performed in 19 clinically healthy foxhound and beagle dogs. Every 5 minutes
      resistance index and pulsatility index as well as invasive blood pressure were
      measured and digitally recorded. RESULTS: Within 5 minutes after induction of
      anaesthesia a transient increase of the mean arterial blood pressure occurred.
      After 10 minutes the blood pressure decreased to the initial value and remained
      essentially constant to the end of the investigation. Resistance index and
      pulsatility index showed a similar behaviour: After a small initial decrease
      during the first 5 minutes both parameters displayed a significant increase. This
      rise was very pronounced up to approximately 15 minutes and then flattened
      significantly until the end of the test period after 30 minutes. The values
      corresponded to those found in vessel stenosis. CONCLUSION AND CLINICAL
      RELEVANCE: Due to the described changes this type of anaesthesia should not be
      used in dogs with nephropathy, even though the results of this experimental study
      might not be necessarily transferable to the clinical patient.

PMID- 22143625
TI  - [Hypoadrenocorticism without classic electrolyte abnormalities in seven dogs].
AB  - OBJECTIVE: Evaluation of all dogs with hypoadrenocorticism (hAC) without classic
      electrolyte abnormalities that had been admitted during the previous 3.75 years.
      MATERIAL AND METHODS: Criteria for inclusion in this study were a confirmed
      diagnosis of hypoadrenocorticism (cortisol concentration before and after ACTH
      application <2 ug/dl) accompanied by a normal sodium:potassium ratio (>= 27).
      Hyperkalaemic animals or those with a history of glucocorticoid, trilostane or
      mitotane administration were excluded. Information including signalement,
      history, physical examination, results of complete blood count, serum biochemical
      analysis, ACTH stimulation test, other laboratory tests and diagnostic imaging
      findings as well as information on the therapy were evaluated. Outcome,
      management and development of electrolyte shifts were assessed by owner telephone
      contact. RESULTS: Seven dogs (among those two poodles) fulfilled the inclusion
      criteria. The median age was 3.6 years. The most common clinical signs observed
      were diarrhoea, vomiting, inappetence and lethargy. The median sodium-potassium
      ratio was 38 (27-41). One dog developed electrolyte abnormalities after 5 months.
      Prednisolone was given to five dogs while one dog received fludrocortisone. In
      one dog repeating of the ACTH stimulation test was recommended before the
      initiation of therapy. One dog was euthanized because of other problems 21 months
      after diagnosis. The other patients responded well to therapy and are in a good
      general condition at present. Two of them occasionally have diarrhoea. CONCLUSION
      AND CLINICAL RELEVANCE: Atypical hAC is an important disease in dogs with
      recurrent chronic gastrointestinal signs seen mainly in young animals with non
      specific historical and physical findings. Therefore, an ACTH stimulation test
      should be considered before invasive diagnostic tests like endoscopy are
      performed in these patients. Since some dogs with primary hAC eventually develop
      classical electrolyte abnormalities serum electrolyte concentrations should be
      monitored regularly.

PMID- 22143626
TI  - [Reference ranges for biochemical parameters in guinea pigs for the
      Vettest(r)8008 blood analyzer].
AB  - OBJECTIVE: Studies to establish reference ranges for blood chemistry in guinea
      pigs are scarce and always apply to bench chemistry. Most veterinary surgeries,
      however, use dry chemistry methods for in-house blood analysis, for which no
      reference ranges are available in guinea pigs. In this study, reference ranges
      for guinea pigs were established by the use of a common dry chemistry blood
      analyzer (Vettest(r)8008). MATERIAL AND METHODS: The animals were pets from
      clients of the Potsdam Veterinary Hospital (24 males, 34 females). The age ranged
      from 8 weeks to 5 years. Plasma samples were prepared for routine blood chemistry
      analysis. The investigation comprised 20 parameters (see below). Reference ranges
      were established via SPSS Statistics 17.0 from 2.5%- and 97.5%-percentiles.
      RESULTS: Enzymes: alkaline phosphatase: 50.80-328.10 U/l; alanine
      aminotransferase: 41.45-165.35 U/l; amylase: 726.93-1831.55 U/l; aspartate
      aminotransferase: 25.25 to 349.23 U/l; creatine kinase: 66.13-1255.40 U/l; gamma
      glutamyl transferase: 0.45-90.75 U/l; lactate dehydrogenase: 5.61-1503.00 U/l,
      lipase: no measurable activity. Substrates: albumin: 17.45-31.65 g/l; ammonia:
      4.80-225.30 mmol/l; cholesterol: 0.00-2.06 mmol/l; creatinine: 23.90 to 73.45
      umol/l; total bilirubin: 2.00-17.60 umol/l; total protein: 50.00-70.85 g/l;
      glucose: 4.62-19.55 mmol/l; blood urea nitrogen: 2.04-11.28 mmol/l;
      triglycerides: 0.46-4.23 mmol/l. Globulins results by calculation: 30.43-42.00
      g/l. Electrolytes: anorganic phosphate: 0.72-2.12 mmol/l, calcium: 2.58-3.16
      mmol/l; magnesium: 0.72 to 1.60 mmol/l. CONCLUSIONS: Some major differences were
      found between the results of three recent studies and the present study,
      respectively. This leads to the conclusion that reference ranges obtained by
      differing methods are not necessarily useful for the veterinary in-house
      laboratory. Instead, in-house analyzers require their own specific reference
      ranges. Possible reasons for the differences in reference ranges of the compared
      studies may be due to undetected subclinical diseases and the use of differing
      chemical or statistical methods.

PMID- 22143627
TI  - [Reactive and neoplastic histiocytic diseases in the dog].
AB  - There are different histiocytic diseases in dogs that are characterized by the
      proliferation of histiocytic cells (macrophages and myeloid dendritic cells).
      Histiocytic diseases can be devided into neoplastic (cutaneous histiocytoma
      complex, histiocytic sarcoma, dendritic cell leukaemia) and reactive forms
      (reactive histiocytosis, haemophagocytic syndrome). All subtypes of the cutaneous
      histiocytoma complex (cutaneous histiocytoma, metastatic histiocytoma and
      Langerhans' cell histiocytosis) are of Langerhans' cell origin. Histiocytoma,
      which is a solitary tumour of the skin in young dogs, shows spontaneous
      regression in most cases. Occasionally, metastasis to lymph nodes can be seen
      (metastatic histiocytoma). Only one dog with Langerhans' cell histiocytosis has
      been described and was euthanized. Histiocytic sarcoma, which arises from myeloid
      dendritic cells, can be classified as localised histiocytic sarcoma or
      disseminated histiocytic sarcoma. Another form of histiocytic sarcoma -
      haemophagocytic histiocytic sarcoma - is derived from macrophages. Histiocytic
      sarcoma displays a very aggressive clinical course and has a poor prognosis.
      Breed predispositions have been reported for the disseminated and haemophagocytic
      form of histiocytic sarcoma in Bernese mountain dogs, Rottweilers and
      varoiusretrievers. In contrast, reactive histiocytosis (cutaneous and systemic
      forms) develops by reactive proliferation of interstitial dendritic cells. In
      systemic histiocytosis, breed predilections are similar to histiocytic sarcoma.
      Haemophagocytic syndrome develops as a consequence of proliferation of activated
      macrophages in different tissues. Prognosis in general is moderate to poor and
      depends on the origin of the underlying disease process.

PMID- 22143628
TI  - [Surgical treatment of aortic thrombosis in a dog].

PMID- 22143629
TI  - Fibroepithelial hyperplasia in an entire male cat: cytologic and
      histopathological features.

PMID- 22143630
TI  - [A rare clinical form of Marek's Disease (cutaneous form) in ornamental fowl].

PMID- 22143632
TI  - Frequency of mild traumatic brain injury in Iraq and Afghanistan: are we
      measuring incidence or prevalence?
AB  - OBJECTIVE: : Rates of mild traumatic brain injury (mTBI) differ considerably
      between US and UK forces, despite similar methodology and similar exposure risks.
      We assessed, in the UK forces, if the differences in rates based on last
      deployment can be explained by differences in deployment length, given that US
      forces deploy for approximately twice as long as UK forces. PARTICIPANTS: : A
      total of 3763 personnel deployed to Iraq or Afghanistan who completed a
      questionnaire between 2007 and 2009. MAIN OUTCOME MEASURES: : Mild traumatic
      brain injury in the last deployment contrasted to current posttraumatic stress
      disorder, psychological distress (General Health Questionnaire-12), multiple
      physical symptoms, and alcohol misuse. RESULTS: : In the Army and Royal Marines,
      there was an association between length of deployment (per month) and mTBI (odds
      ratio: 1.31, 95% confidence interval: 1.13-1.51), which remained significant
      after adjustment for confounders (odds ratio: 1.25, 95% confidence interval: 1.08
      1.45). No other outcome was associated with length of deployment. Results based
      on the total sample were similar to those in the Royal Marine and Army sample,
      except for adjusted multiple physical symptoms. CONCLUSIONS: : Comparisons of
      mTBI rates should take account of length of deployment when based on last
      deployment. Doing so reduces but does not eliminate the differences between UK
      and US forces.

PMID- 22143633
TI  - Sexual behavior before and after pregnancy detection in four microbicide trials.
AB  - Vaginal microbicide gel trials for HIV prevention may require withdrawal of study
      product when a woman becomes pregnant. We assessed the potential impact of
      withdrawals in four trials by comparing self-reported sexual behavior pre- and
      post-pregnancy detection: (1) behavior in the month prior to positive pregnancy
      test versus behavior reported at the subsequent monthly visit; (2) behavior
      changes according to pregnancy status at the subsequent visit (continuing
      pregnancy versus not); (3) average sexual behaviors reported for all months prior
      to pregnancy detection versus all months after pregnancy was no longer detected;
      and (4) behavior changes among participants never testing positive for pregnancy.
      Pregnancy detection was associated with immediate reductions in self-reported
      numbers of partners and sex acts. The proportion of acts in which study gel was
      used following a negative pregnancy test did not return to pre-pregnancy levels.
      Pregnancies complicate the conduct and interpretation of vaginal microbicide
      trials when product must be withdrawn.

PMID- 22143659
TI  - [Aortic insufficiency: diagnosis and haemodynamics, incidence in an unselected
      group of Irish Wolfhounds].
AB  - Common causes of acute and chronic aortic regurgitation are discussed. The main
      diagnostic tool is focused on echocardiographic evaluation and determination of
      the severity. A group of 50 Irish Wolfhounds underwent a clinical,
      electrocardiographic and echocardiographic examination. In 40 dogs an abnormal
      finding due to heart disease could be detected, which comprised an aortic
      insufficiency in 23 of the dogs. Only in one case was a severe degree of aortic
      regurgitation found, while in nine cases a moderate and in 13 dogs a mild degree
      was found. The occurrence of additional findings as atrial and chamber
      enlargement, mitral valve insufficiency, and atrial fibrillation correlated with
      the severity of the aortic insufficiency.

PMID- 22143634
TI  - OPRM1 and diagnosis-related posttraumatic stress disorder in binge-drinking
      patients living with HIV.
AB  - Posttraumatic stress disorder (PTSD) has been linked to numerous negative
      outcomes in persons living with HIV (PLH) and there is evidence that PTSD
      symptoms may play a role in maintaining alcohol use problems. The opioid receptor
      mu-1 (OPRM1) gene may play a role in both PTSD and alcohol use. We examined the
      association between PTSD and drinking motives as well as variation in the OPRM1
      as a predictor of both PTSD and drinking motives in a sample of 201 PLH reporting
      recent binge drinking. Self-reported PTSD symptom severity was significantly
      associated with drinking motives for coping, enhancement, and socialization.
      OPRM1 variation was associated with decreased PTSD symptom severity as well as
      enhancement motives for drinking.

PMID- 22143660
TI  - [Quality of life and life expectancy of dogs undergoing chemotherapy for
      malignant lymphoma. An owner survey].
AB  - OBJECTIVE: The outcome of palliative chemotherapy in dogs with lymphoma was
      evaluated. Special emphasis was placed on the quality of life during
      chemotherapy. In addition, factors which were important for the owners in
      estimating their dogs' quality of life and for the assessment of therapy were
      recorded. MATERIAL AND METHODS: In a retrospective study the owners of 207 dogs
      that had undergone chemotherapy at the Clinic of Small Animal Medicine,
      University of Munich during the previous 13 years, were asked about their dogs'
      course of disease and therapy by using a specially designed questionnaire.
      RESULTS: A total of 123 owners (59.4%) responded to the questionnaire. Quality of
      life improved in 64 dogs (53.3%) during chemotherapy. In only 24 dogs (20.0%) was
      a decline in the quality of life recorded, that directly correlated with
      remission status and side effects. The overall remission rate in dogs undergoing
      chemotherapy was 83.7%. CONCLUSION: Despite treatment complications, the majority
      of the owners (65.0%) were satisfied by the chemotherapy of their dogs. Ninety
      owners (73.2%) would have treated their animal with chemotherapy again; for this
      decision prolonged survival was an important factor. CLINICAL RELEVANCE: In dogs
      with cancer the quality of life needs to be monitored constantly during
      palliative chemotherapy. This assessment helps to choose the appropriate
      chemotherapy protocol and facilitates the decision on further treatment options
      by the owner and the veterinarian.

PMID- 22143661
TI  - [Feline panleukopenia - different course of disease in cats younger than versus
      older than 6 months of age?].
AB  - OBJECTIVE: The aim of this study was to evaluate differences between young cats
      (< 6 months) and adult cats (>= 6 months) with feline panleukopenia with respect
      to clinical signs, laboratory abnormalities, environmental conditions,
      vaccination status, and outcome. MATERIAL AND METHODS: Medical records of 244
      cats diagnosed with panleukopenia between 1990 and 2007 at the Clinic of Small
      Animal Medicine, Ludwig-Maximilians University of Munich, Germany, were evaluated
      retrospectively. Cats that tested positive for feline panleukopenia virus (FPV)
      via electron microscopy, polymerase chain reaction (blood, faeces), antigen ELISA
      (faeces), or that had histopathological lesions consistent with panleukopenia at
      necropsy were included. Cats were excluded if they had been vaccinated against
      FPV within 3 weeks before admission. RESULTS: In total 43.3% of cats were older
      than 6 months. There was no statistically significant difference between the two
      age groups regarding outcome, breed, sex, environmental conditions, vaccination
      status, clinical signs, and laboratory parameters with the exception of
      haematocrit: cats < 6 months had significantly lower haematocrit on the day of
      presentation than cats >= 6 months. CONCLUSIONS AND CLINICAL RELEVANCE: Feline
      panleukopenia is predominantly in young cats, but older cats can also suffer from
      the disease. Although young cats are at a higher risk of infection, cats at the
      age of < 6 months suffering from clinical disease do not have a higher risk of
      death. Clinical presentation, laboratory abnormalities, prognosis, and outcome
      did not differ significantly between cats younger versus older than 6 months of
      age.

PMID- 22143662
TI  - [Measurement of thiamine concentration in the cat using high pressure liquid
      chromatography].
AB  - OBJECTIVE: Thiamine deficiency in cats frequently leads to a dysfunction of the
      central nervous system including vestibular signs with fatal outcome in untreated
      cases. The aim of the present study was to directly measure thiamine
      concentrations using high pressure liquid chromatography (HPLC) in feline blood
      samples and to evaluate values in healthy and diseased cats. MATERIAL AND
      METHODS: Blood samples (1 ml EDTA-whole blood) from 193 cats were analysed for
      total thiamine and thiamine diphosphate using HPLC. For the interpretation of the
      results cats were retrospectively assigned to six groups: A) healthy cats, B)
      cats with diseases of the gastrointestinal tract, C) cats with different traumas
      not affecting the gastrointestinal tract, D) cats with inappetence, cats with
      central vestibular signs and normal (E) or low values of thiamine (F),
      respectively. RESULTS: In animals of group F no obvious cause for the vestibular
      signs was found and spontaneous recovery after thiamine application occurred in
      three cats. Therefore thiamine deficiency was a highly likely clinical diagnosis.
      Total thiamine concentration (mean 48.2 ug/l, standard deviation +/- 22.6) of
      group F significantly differered from the other groups (group A-D: p<0.01, group
      E: p<0.001). Comparable results were obtained for thiamine diphosphate. However,
      low total thiamine values were also found in cats with inappetence without any
      neurological signs. CONCLUSION AND CLINICAL RELEVANCE: In the present study a
      method for direct measurement of thiamine formerly established for ruminants was
      evaluated for cats. A more accurate and objective clinical diagnosis of thiamine
      deficiency is feasible in cats with values less than 50 ug/l and typical clinical
      signs. In animals with values of total thiamine levels between 50-70 ug/l a
      prophylactic substitution of thiamine can be discussed.

PMID- 22143664
TI  - [Comparison of the image quality of conventional and digital radiography in
      lizards. Mammography technique versus digital detector system].
AB  - OBJECTIVE: A conventional high-resolution screen-film system (Film Kodak MIN-R S,
      Kodak MIN-R 2000) was compared with an indirect digital detector system (Varian
      PaxScan 4030E) for use in radiography of lizards. MATERIAL AND METHODS: A total
      of 20 bearded dragons (Pogona vitticeps ) with body masses between 123 g and 487
      g were investigated by using conventional and digital image acquisition
      techniques. The digital image was taken with the same dose as well as half the
      dose of the conventional radiograph. The study was conducted semi-blinded as the
      x-ray images were encoded and randomised. Five veterinarians with clinical
      experience in reptile medicine served as observers. Exactly defined structures in
      three anatomical regions were assessed using a three-step scale. Furthermore, the
      overall quality of the respective region was evaluated using a five-step scale.
      Evaluation of the data was done by visual grading analysis. RESULTS: None of the
      structures examined was assessed to be of significantly inferior quality on the
      digital images in comparison to the conventional radiographs. The majority of the
      results demonstrated an equal quality of both systems. For assessment of the lung
      tissue and the pulmonary vessels as well as the overall assessment of the lung,
      the digital radiographs with full dose were rated to be significantly superior in
      comparison to the film-screen system. Furthermore, the joint contours of the
      shoulder and cubital joints and the overall assessments of the humerus and the
      caudal coelomic cavity were rated significantly better on digital images with
      full dose compared to those with reduced dose. CONCLUSIONS: The digital flat
      panel detector technique examined in this study is equal or superior to the
      conventional high-resolution screen-film system used. Nevertheless, the
      practicability of a dose reduction is limited in bearded dragons. CLINICAL
      RELEVANCE: Digital imaging systems are progressively being used in veterinary
      practice. The results of the study demonstrate the useful application of the
      digital detector systems in lizards.

PMID- 22143663
TI  - [Endocrinologic studies of male psittacine birds for the evaluation of their
      reproductive status].
AB  - OBJECTIVE: Evaluating methods of hormone measurement in different specimens of
      male parrots in order to assess their reproductive status and stress axis.
      MATERIAL AND METHODS: Cockatiels and rose-ringed parakeets were chosen as
      psittaciforme representatives and their endocrine profiles were examined. In
      various pre-experiments, suitable techniques for the determination of
      testosterone in plasma, saliva and faeces of male parrots were established.
      Before analysing the samples by enzyme immunoassay, blood and faeces were
      extracted using diethyl ether, while saliva could be tested without extraction.
      Based on the excretion of mainly conjugated testosterone metabolites, parrots'
      faecal samples were also hydrolysed with beta-glucuronidase/arylsulfatase before
      extraction. In addition, the levels of the stress hormone corticosterone were
      determined by radioimmunoassay in order to assess possible relationships between
      stress and the secretion of testosterone. RESULTS: The examined psittacine
      species displayed different seasonal secretion patterns for both testosterone and
      corticosterone. Cockatiels had maximum plasma testosterone levels in February, in
      contrast, rose-ringed parakeets showed highest concentrations in November. As a
      consequence of cumulative excretion, both species showed much higher faecal than
      plasma testosterone concentrations. In rose-ringed parakeets, the levels of
      corticosterone in plasma were exceptionally high compared to the cockatiels.
      CONCLUSION: According to this study, we have been able to establish suitable
      methods for testosterone analysis in blood and faeces of cockatiels and rose
      ringed parakeets, supporting the assessment of their reproductive status. At
      present saliva does not appear to be an ideal medium for reliable hormone level
      measurement, thus further investigations are required concerning this subject.
      CLINICAL RELEVANCE: By means of process analysis, it will be possible to detect
      increasing testosterone levels and/or pathological alterations, which could be
      considered in breeding programmes.

PMID- 22143665
TI  - Utero-ovarian torsion in a bitch and subsequent fertility after unilateral
      ovariohysterectomy.

PMID- 22143666
TI  - [Intraocular mast cell tumor in a dog. A case report].

PMID- 22143667
TI  - [Mucosal polyps as the cause of esophageal obstruction in a parrot. A
      differential diagnosis for the Proventricular Dilatation Syndrome].

PMID- 22143668
TI  - [Ultrasonography of urinary tract diseases in the dog and cat].

PMID- 22143669
TI  - Spectroscopic characterization of the key catalytic intermediate Ni-C in the O2
      tolerant [NiFe] hydrogenase I from Aquifex aeolicus: evidence of a weakly bound
      hydride.
AB  - Ni-C in the O(2)-tolerant hydrogenase I from Aquifex aeolicus binds a hydride
      weaker than that in O(2)-sensitive hydrogenases. This is in line with the
      enhanced light-sensitivity of Ni-C, greater lability of the hydride complex and
      increased catalytic redox potentials relevant to bio-H(2) oxidation.

PMID- 22143670
TI  - Expansion of NK cells from cord blood with antileukemic activity using GMP
      compliant substances without feeder cells.

PMID- 22143671
TI  - The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute
      myeloid leukemia.
AB  - The serine/threonine kinase mammalian target of rapamycin (mTOR) is crucial for
      cell growth and proliferation, and is constitutively activated in primary acute
      myeloid leukemia (AML) cells, therefore representing a major target for drug
      development in this disease. We show here that the specific mTOR kinase inhibitor
      AZD8055 blocked mTORC1 and mTORC2 signaling in AML. Particularly, AZD8055 fully
      inhibited multisite eIF4E-binding protein 1 phosphorylation, subsequently
      blocking protein translation, which was in contrast to the effects of rapamycin.
      In addition, the mTORC1-dependent PI3K/Akt feedback activation was fully
      abrogated in AZD8055-treated AML cells. Significantly, AZD8055 decreased AML
      blast cell proliferation and cell cycle progression, reduced the clonogenic
      growth of leukemic progenitors and induced caspase-dependent apoptosis in
      leukemic cells but not in normal immature CD34+ cells. Interestingly, AZD8055
      strongly induced autophagy, which may be either protective or cell death
      inducing, depending on concentration. Finally, AZD8055 markedly increased the
      survival of AML transplanted mice through a significant reduction of tumor
      growth, without apparent toxicity. Our current results strongly suggest that
      AZD8055 should be tested in AML patients in clinical trials.

PMID- 22143672
TI  - Epigenetic regulation of miRNA genes in acute leukemia.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that can negatively
      regulate gene expression at the post-transcriptional level. miRNA expression
      patterns are regulated during development and differentiation of the
      hematopoietic system and have an important role in cell processes such as
      proliferation, apoptosis, differentiation or even in tumorigenesis of human
      tumors and in particular of hematological malignancies such as acute leukemias.
      Various miRNAs and their functions have been intensively studied in acute
      leukemias but the mechanisms that control their expression are largely unknown
      for the majority of aberrantly expressed miRNAs. miRNA expression can be
      regulated by the same genetic mechanism that modulate protein coding genes such
      as mutation, deletion, amplification, loss of heterozygosity and translocations.
      In this review we focus on the regulation of miRNAs in acute leukemias mediated
      by alterations in epigenetic mechanisms such as DNA methylation and histone code,
      describing the role of these alterations in the pathogenesis, diagnosis and
      prognosis of acute leukemias and their possible use as new therapeutic targets
      and biomarkers.

PMID- 22143673
TI  - Simultaneous detection of piroplasma infections in field Haemaphysalis
      qinghaiensis ticks by reverse line blotting.
AB  - Piroplasmosis is caused by tick-borne haemoprotozoan parasites in the genera of
      Theileria and Babesia, in which numbers of agents are highly pathogenic for
      cattle, sheep and goats. We developed a reverse line blot (RLB) assay for
      detection and differentiation of four different parasites, in which 18S ribosomal
      RNA gene sequence was amplified with a set of universal primers specific for all
      members in the genera of Theileria and Babesia; and the probes were designed on
      the basis of hypervariable region 4 (V4 region) of 18S rRNA gene. Three Theileria
      and one Babesia can be detected simultaneously on this system and it was
      sensitive to detect a parasitemia level between 10(-5) and 10(-8)%. A total of
      149 Haemaphysalis qinghaiensis ticks collected from Lintan County of Gannan
      Tibetan Autonomous Region was tested by RLB. Among these, 136 tick samples were
      also tested by a nested PCR assay developed previously. After comparison of these
      results, it showed that more T. luwenshuni was detected in RLB assay, while more
      T. uilenbergi was detected in H. qinghaiensis ticks by nested PCR. The RLB has
      shown capability for simultaneous detection of four species of piroplasm in H.
      qinghaiensis ticks, indicating its usefulness for epidemiological studies of
      piroplasmosis.

PMID- 22143674
TI  - DHRS7c, a novel cardiomyocyte-expressed gene that is down-regulated by adrenergic
      stimulation and in heart failure.
AB  - AIMS: Although cardiac diseases account for the highest mortality and morbidity
      rates in Western society, there is still a considerable gap in our knowledge of
      genes that contribute to cardiac (dys)function. Here we screened for gene
      expression profiles correlated to heart failure. METHODS AND RESULTS: By
      expression profiling we identified a novel gene, termed DHRS7c, which was
      significantly down-regulated by adrenergic stimulation and in heart failure
      models. Dhrs7c is a short chain dehydrogenase/reductase (SDR) and is localized to
      the endo/sarcoplasmic reticulum. Dhrs7c is strongly conserved in vertebrates, and
      mRNA and protein expression levels were highest in heart and skeletal muscle
      followed by skin, but were not detectable in other organs. In vitro, both alpha-
      and beta-adrenergic stimulation repressed Dhrs7c expression in neonatal
      cardiomyocytes and this could be mimicked by the direct activation of protein
      kinase C and adenylate cyclase, the respective intracellular targets of these
      hormones. In contrast, endothelin-1, which also provoked strong hypertrophy
      development in vitro, did not repress Dhrs7c expression. The latter suggests
      adrenergic specificity and indicates that down-regulation is not a prerequisite
      for hypertrophy development. In vivo adrenergic stimulation could also down
      regulate Dhrs7c expression. Finally, we confirmed that expression was also down
      regulated in two different models of failure and, importantly, also in biopsies
      from human heart failure patients. CONCLUSION: Our results show that the
      expression of Dhrs7c, a novel endo/sarcoplasmic reticulum-localized SDR, is
      inversely correlated with adrenergic stimulation and heart failure development.

PMID- 22143675
TI  - Normativity unbound: liminality in palliative care ethics.
AB  - This article applies the anthropological concept of liminality to reconceptualize
      palliative care ethics. Liminality possesses both spatial and temporal
      dimensions. Both these aspects are analyzed to provide insight into the
      intersubjective relationship between patient and caregiver in the context of
      palliative care. Aristotelian practical wisdom, or phronesis, is considered to be
      the appropriate model for palliative care ethics, provided it is able to account
      for liminality. Moreover, this article argues for the importance of liminality
      for providing an ethical structure that grounds the doctrine of double effect and
      overcomes the impasse of phronesis in the treatment of the terminally ill.

PMID- 22143677
TI  - Combined photodynamic therapy with verteporfin and intravitreal anti-vascular
      endothelial growth factor therapy for chronic central serous chorioretinopathy.

PMID- 22143676
TI  - Long-term follow-up of changes in corneal endothelium after primary and secondary
      intraocular lens implantations in children.
AB  - BACKGROUND: To evaluate long-term changes in corneal endothelial cell count and
      morphology after congenital cataract extraction and intraocular lens
      implantation. METHODS: Cataract extraction and posterior chamber intraocular lens
      (IOL) implantation was performed on 54 congenital cataract patients (83 eyes).
      The corneal endothelial cell density (ECD), coefficient of variation (CV),
      hexagonality, and central corneal thickness (CCT) were measured for a
      retrospective analysis of long-term changes in corneal endothelial
      characteristics. RESULTS: The mean age at the time of IOL implantation was 5.00
      (3.62) years [mean (SD)], and the mean follow-up period was 8.83 (1.49) years. In
      a comparison of the treated and normal eyes of patients who underwent unilateral
      surgery, the treated eyes showed a significantly greater CCT (p < 0.05), and
      there was no significant difference in ECD, CV, and hexagonality (p > 0.05). In
      addition, there was no statistically significant difference in the ECD and CCT
      between the primary and secondary IOL implantation groups. CONCLUSIONS: Our
      results did not show any significant corneal endothelial cell loss in congenital
      cataract patients; however, their CCTs were increased.

PMID- 22143678
TI  - Secondary health conditions in individuals aging with SCI: terminology, concepts
      and analytic approaches.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: Utilizing individuals with spinal
      cord injury (SCI) as a representative population for physical disability, this
      paper: (1) reviews the history of the concept of secondary conditions as it
      applies to the health of individuals aging with long-term disabilities; (2)
      proposes a definition of secondary health conditions (SHCs) and a conceptual
      model for understanding the factors that are related to SHCs as individuals age
      with a disability; and (3) discusses the implications of the model for the
      assessment of SHCs and for developing interventions that minimize their
      frequency, severity and negative effects on the quality of life of individuals
      aging with SCI and other disabilities. METHODS: Key findings from research
      articles, reviews and book chapters addressing the concept of SHCs in individuals
      with SCI and other disabilities were summarized to inform the development of a
      conceptual approach for measuring SCI-related SHCs. CONCLUSIONS: Terms used to
      describe health conditions secondary to SCI and other physical disabilities are
      used inconsistently throughout the literature. This inconsistency represents a
      barrier to improvement, measurement and for the development of effective
      interventions to reduce or prevent these health conditions and mitigate their
      effects on participation and quality of life. A working definition of the term
      SHCs is proposed for use in research with individuals aging with SCI, with the
      goal of facilitating stronger evidence and increased knowledge upon which policy
      and practice can improve the health and well-being of individuals aging with a
      disability.

PMID- 22143679
TI  - A more active lifestyle in persons with a recent spinal cord injury benefits
      physical fitness and health.
AB  - STUDY DESIGN: A prospective cohort study. OBJECTIVES: To study the longitudinal
      relationship between objectively measured everyday physical activity level, and
      physical fitness and lipid profile in persons with a recent spinal cord injury
      (SCI). SETTING: A rehabilitation centre in the Netherlands and the participant's
      home environment. METHODS: Data of 30 persons with a recent SCI were collected at
      the start of active rehabilitation, 3 months later, at discharge from inpatient
      rehabilitation, and 1 year after discharge. Physical activity level (duration of
      dynamic activities as % of 24 h) was measured with an accelerometry-based
      activity monitor. Regarding physical fitness, peak oxygen uptake (VO(2)peak) and
      peak power output (POpeak) were determined with a maximal wheelchair exercise
      test, and upper extremity muscle strength was measured with a handheld
      dynamometer. Fasting blood samples were taken to determine the lipid profile.
      RESULTS: An increase in physical activity level was significantly related to an
      increase in VO(2)peak and POpeak, and an increase in physical activity level
      favourably affected the lipid profile. A nonsignificant relation was found with
      muscle strength. CONCLUSION: Everyday physical activity seems to have an
      important role in the fitness and health of persons with a recent SCI. An
      increase in physical activity level was associated with an increase in physical
      fitness and with a lower risk of cardiovascular disease.

PMID- 22143680
TI  - Cervical spinal cord injury due to fall while carrying heavy load on head: a
      problem in Bangladesh.
AB  - STUDY DESIGN: Observational study. SETTING: Centre for the Rehabilitation of the
      Paralysed (CRP), Dhaka, Bangladesh. METHODS: This observational study was
      conducted on 84 patients of Cervical spinal cord injury (CSCI) due to fall while
      carrying heavy load on head. They were admitted at the CRP, Dhaka, Bangladesh
      between January 1999 and December 2001. Relevant personal information,
      neurological status, types of bony injuries and x-ray findings were noted down in
      pre-structured questionnaire. In addition, each subject was interviewed to find
      out the cause of accidental fall while carrying heavy load on head. RESULTS: Age
      of the studied subjects ranged between 10 to 50 years. All were male of whom 79
      (94%) subjects were farmers and/or low cost daily laborers. In all, 72% percent
      of the subjects were carrying 60-80 kg weight on their head when fall occurred. A
      total of 48 (57%) subjects had complete neurological lesion. The most common
      vertebral levels were C5 and C6. So far the mechanism of injury is concerned
      hyper flexion of the cervical spine predominated (61%) over hyperextension (36%).
      CONCLUSION: Fall while carrying heavy load on head is a common cause of CSCI in
      Bangladesh. The victims are mostly young farmers or unskilled day laborers who
      were not habituated to carry heavy load on head.

PMID- 22143681
TI  - Initiation and control of catalytic surface reactions with shaped femtosecond
      laser pulses.
AB  - We report on femtosecond laser-induced catalytic reactions of carbon monoxide and
      hydrogen on single crystal surfaces under high vacuum conditions. Several product
      molecules are synthesized, among them also species for whose formation at least
      three reactants are required. By applying closed-loop optimal control, we
      manipulate these reactions and selectively optimize the ratio of different bond
      forming reaction channels, in contrast to previous quantum control experiments
      aiming at bond-cleavage. Further experiments explore the nontrivial control
      mechanism and its sensitivity to the relative proportion of the two reactant
      gases.

PMID- 22143682
TI  - Oral health status of a population with multiple sclerosis.
AB  - OBJECTIVE: To determine the oral treatment needs of a sample of patients
      diagnosed with multiple sclerosis in the Community of Madrid (Spain). PATIENTS
      AND METHODS: A cross-sectional epidemiological study was carried out with a
      sample of 64 patients who were aged 25 to 77 years. They were distributed into
      homogeneous age groups: < 46 years, 46-54 years and > 54 years. In order to
      evaluate the oral health status and treatment requirements, the parameters and
      guidelines of the WHO were used. RESULTS: The prevalence of caries was 100%, or
      very close in all three groups. As age increased, the morbidity rate decreased,
      but the mortality rate increased considerably. On analyzing gingival health, 65%
      of patients had calculus, 5% bleeding and 30% were healthy. CONCLUSIONS: The DMFT
      index found provided data that was, in general, very similar to that of the
      general population in Spain. However, the gingival health status found
      demonstrated that the population of multiple sclerosis patients requires specific
      assistance.

PMID- 22143683
TI  - Comparative study of upper lip frenectomy with the  CO2 laser versus the Er,
      Cr:YSGG laser.
AB  - OBJECTIVES: To compare upper lip frenulum reinsertion, bleeding, surgical time
      and surgical wound healing in frenectomies performed with the CO2 laser versus
      the Er, Cr:YSGG laser. STUDY DESIGN: A prospective study was carried out on 50
      randomized pediatric patients who underwent rhomboidal resection of the upper lip
      frenulum with either the CO2 laser or the Er,Cr:YSGG laser. Twenty-five patients
      were assigned to each laser system. All patients were examined at 7, 14, 21 days
      and 4 months after the operation in order to assess the surgical wound healing.
      RESULTS: Insertion of the frenulum, which was preoperatively located between the
      upper central incisors, migrated to the mucogingival junction as a result of
      using both laser systems in all patients. Only two patients required a single
      dose of 650 mg of paracetamol, one of either study group. CO2 laser registered
      improved intraoperative bleeding control results and shorter surgical times. On
      the other hand, the Er,Cr:YSGG laser achieved faster healing. CONCLUSIONS: Upper
      lip laser frenectomy is a simple technique that results in minimum or no
      postoperative swelling or pain, and which involves upper lip frenulum reinsertion
      at the mucogingival junction. The CO2 laser offers a bloodless field and shorter
      surgical times compared with the Er,Cr:YSGG laser. On the other hand, the
      Er,Cr:YSGG laser achieved faster wound healing.

PMID- 22143684
TI  - Epidemiology of the sarcomas of the jaws  in a Peruvian population.
AB  - OBJECTIVE: Analysis of the clinical characteristics of patients with Sarcomas of
      the Jaws treated in the "Instituto Nacional de Enfermedades Neoplasicas. Dr.
      Eduardo Caceres Graziani" from 1952-2007. STUDY DESIGN: Review of 155 clinical
      records of patients with Sarcomas of the Jaws and record of age, gender, size,
      location, clinical symptoms and signs, histopathological diagnoses and type of
      treatment. The data obtained were analyzed by means of Student's statistical t
      test, Fisher and Friedman's test. RESULTS: Analysis of 155 Sarcomas of the Jaws.
      The average age of patients was 36.8 years old (range: 1-80 years); the female
      gender was the most frequent (52.9%); the average tumor size was 5.5 cm; in upper
      jaw 54.84% occurred and 45.16% in the lower jaw; the predominant sign was facial
      asymmetry (87.74%) and the predominant symptom: pain (63.23%). The most frequent
      diagnosis was Osteosarcoma 50.3% followed by Chondrosarcoma 18%. Surgery plus
      radiation therapy was the treatment type of choice with 21.94% of cases.
      CONCLUSION: The results of this study demonstrate the delayed diagnosis and
      facial asymmetry and pain appear as the most important events for the diagnosis
      of Sarcomas of the Jaws.

PMID- 22143685
TI  - Maxillofacial metastasis of genitourinary origin. A report of 3 cases and review
      of the literature.
AB  - INTRODUCTION: The maxillofacial region can harbour a wide range of primary
      tumours, as well as secondary tumours spreading from distant sites. Rare, though
      nevertheless important among the latter are genitourinary tumours, such as clear
      cell renal carcinoma and cervical cancer. Diagnosis of the maxillofacial
      metastasis sometimes precedes that of the original site, though in other cases
      the metastasis may arise many years after treatment of the primary tumour. CASE
      REPORT: We present three cases of maxillofacial metastasis of genitourinary
      tumours, two clear cell renal adenocarcinoma and squamous cell carcinoma of the
      uterine cervix. The patients were referred our hospital service for diagnosis and
      treatment, after having been initially evaluated for buccodental symptoms.
      DISCUSSION: The appearance of a maxillofacial tumour, initially with the aspect
      of a primary tumour, may sometimes be the consequence of haematogenous
      dissemination from another site, such as these surprising cases originating in
      the genitourinary area. If disseminated metastatic disease is suspected, an
      extensive oncological screening should be done to evaluate the best therapeutic
      option in each patient.

PMID- 22143686
TI  - Comparison of the effects of rapid maxillary expansion  and surgically assisted
      rapid maxillary expansion  in the sagittal, vertical, and transverse planes.
AB  - OBJECTIVE: The aim of this study was to evaluate and compare the effects of rapid
      maxillary expansion (RME) and surgically assisted RME (SARME) in the sagittal,
      vertical, and transverse planes. STUDY DESIGN: Orthodontic records of 28 patients
      were selected retrospectively and divided into two treatment groups. Group 1
      comprised 14 patients (4 boys, 10 girls, mean age 14.2 +/- 0.74 years) who had
      been treated with RME. Group 2 comprised 14 patients (4 boys, 10 girls, mean age
      19.6 +/- 2.73 years) who had been treated with SARME. Measurements were performed
      on lateral and posteroanterior cephalograms and dental casts obtained before (T0)
      and after (T1) expansion. RESULTS: Statistically significant differences were
      found in soft tissue convexity angle, anterior face height, and upper nasal width
      in group 1, and in U1-NA length and posterior face height measurements in group 2
      (P<.05). In both groups significant increases were found in interpremolar,
      intermolar, maxillary, and lower nasal widths and in anterior lower face height
      (P<.01). Statistically significant intergroup differences were found in the ANB
      angle (P<.05) and maxillary intercanine (P<.01) measurements. CONCLUSION: With
      both RME and SARME, successful expansion of maxillary dentoalveolar structures
      and nasal cavity and palatal widening were achieved. Sagittal plane effects of
      SARME were similar to those of RME on dental skeletal and airway measurements.

PMID- 22143687
TI  - The role of mast cells on angiogenesis in oral squamous cell carcinoma.
AB  - OBJECTIVE: Angiogenesis or neovascularization has long been known to aid in
      progression and metastasis of malignant tumors. Tumor angiogenesis is a complex
      event mediated by angiogenic factors released from cancer cells and or by host
      immune cells. Mast cells may induce tumor progression and potentiate metastasis
      by stimulating angiogenesis. The purpose of the present study was to validate
      topographic distribution of micro vessel density (MVD) and mast cell density
      (MCD) and help to elucidate the possible role of mast cells in tumor angiogenesis
      and correlating this with advanced disease parameters. . STUDY DESIGN: MVD and
      MCD were investigated in tumor specimens from 30 patients diagnosed with
      different histologic grades of oral squamous cell carcinoma (OSCC). Intratumor
      vessels were stained with collagen Type IV antibody and mast cells with Toluidine
      blue before being measured by light microscopy. RESULTS: There was a significant
      correlation between MVD and disease progression and number of blood vessels
      increased from well to poorly differentiated OSCC where as MCD decreased.
      CONCLUSIONS: These findings suggest that angiogenesis indeed occur in OSCC and
      might be used as an index to inflect the aggression of the disease however mast
      cells make up only a part of complex process of angiogenesis along with other
      factors secreted by tumor.

PMID- 22143688
TI  - The prevalence of pulp stones in a Turkish population.  A radiographic survey.
AB  - OBJECTIVES: The goal of this retrospective study was to determine the prevalence
      of pulp stones in a Turkish population. Any possible associations between pulp
      stones and gender, tooth type and dental arch were also evaluated. STUDY DESIGN:
      Four hundred and sixty nine patients' bitewing radiographs which were reached
      through the patient database of Erciyes University Dentistry School, Department
      of Oral Diagnosis and Radiology were examined. Of these 469 subjects whose mean
      age was 24( +/- 10.7), 302 were females and 167 were males. A total of 6,926
      teeth were examined during this study. Pulp stones were recorded as present or
      absent and any relations with gender, tooth type and dental arch were noted.
      RESULTS: Pulp stones were identified in 270 (57.6 %) of the subjects and in 1,038
      (15 %) of the teeth examined. Their presence were seldom found in the premolars
      (9.07%) but was much higher in the molars (90.92 %). Pulp stone occurrence was
      significantly more common in the first molars than in the second molars, and in
      the first premolars than in the second premolars in each dental arch. Their
      occurrence was higher in the maxilla than in the mandible for each tooth type. No
      difference between the two genders could be identified. CONCLUSION: Pulp stones
      are not only incidental radiographic findings of the pulp tissue but may also be
      an indicator of some serious underlying disease. On the other hand, they may
      provide useful information to predict about the susceptibility of patients for
      other dystrophic soft tissue calcifications such as urinary calculi and calcified
      atheromas. However, further study on this issue is needed.

PMID- 22143689
TI  - Post-traumatic trigeminal neuropathy. A study of 63 cases.
AB  - INTRODUCTION: Trigeminal neuropathy is most often secondary to trauma. The
      present study explores the underlying causes and the factors that influence
      recovery. MATERIAL AND METHODS: A retrospective case study was made involving 63
      patients with trigeminal neuropathy of traumatologic origin, subjected to follow
      up for at least 12 months. RESULTS: Fifty-four percent of all cases were
      diagnosed after mandibular third molar surgery. In 37 and 19 patients the sensory
      defect was located in the territory innervated by the mental and lingual nerve,
      respectively. Pain was reported in 57% of the cases, and particularly among the
      older patients. Regarding patient disability, quality of life was not affected in
      three cases, while mild alterations were recorded in 25 subjects and severe
      alterations in 8. Partial or complete recovery was observed in 25 cases after 6
      months, and in 32 after one year. There were few recoveries after this period of
      time. Recovery proved faster in the youngest patients, who moreover were the
      individuals with the least pain. CONCLUSION: Our patients with trigeminal
      neuropathy recovered particularly in the first 6 months and up to one year after
      injury. The older patients more often suffered pain associated to the sensory
      defect. On the other hand, their discomfort was more intense, and the patients
      with most pain and the poorest clinical scores also showed a comparatively poorer
      course.

PMID- 22143690
TI  - Electrochemical corrosion assessment of RaCe and Mtwo rotary  nickle-titanium
      instruments after clinical use and sterilization.
AB  - AIM: The aim of the present study was to electrochemically evaluate corrosion
      resistance of RaCe and Mtwo files after repeated sterilization and preparation
      procedures. STUDY DESIGN: A total of 450 rotary files were used. In the working
      groups, 72 files from each file type were distributed into 4 groups. RaCe and
      Mtwo files were used to prepare one root canal of the mesial root of extracted
      human mandibular first molars. The procedure was repeated to prepare 2 to 8
      canals. The following irrigation solutions were used: group 1, RaCe files with
      2.5% NaOCl; group 2, RaCe files with normal saline; group 3, Mtwo files with 2.5%
      NaOCl; and group 4, Mtwo files with normal saline in the manner described. In
      autoclave groups, 72 files from each file type were evenly distributed into 2
      groups. Files were used for a cycle of sterilization without the use of files for
      root canal preparation. Nine new unused files from each file type were used as
      controls. Then the instruments were sent for corrosion assessment. Mann-Whitney U
      and Wilcoxon tests were used for independent and dependent groups, respectively.
      RESULTS: Statistical analysis indicated that there were significant differences
      in corrosion resistance of files associated with working and autoclave groups
      between RaCe and Mtwo file types (p<0.001). CONCLUSIONS: Corrosion resistance of
      #25, #30, and #35 Mtwo files is significantly higher than that in RaCe files with
      similar sizes.

PMID- 22143691
TI  - Evaluation of the anaesthetic properties and tolerance of 1:100,000  articaine
      versus 1:100,000 lidocaine. A comparative  study in surgery of the lower third
      molar.
AB  - OBJECTIVES: To evaluate the anaesthetic properties and tolerance of articaine
      versus lidocaine at equal vasoconstrictor concentration. STUDY DESIGN: A total of
      96 male and female patients who underwent surgical treatment of the lower third
      molar participated. Patients were randomly assigned to articaine hydrochloride
      with epinephrine 1:100,000 and lidocaine hydrochloride with epinephrine
      1:100,000. The variables analysed were latency period, duration of anaesthetic
      effect, tolerance and adverse reactions. RESULTS: Both the latency period and the
      duration of anaesthetic effect were greater for articaine, although the
      differences were not statistically significant. Latency: mean difference of 2.70
      +/- 2.12 minutes (95%CI of -1.51 minutes - 6.92 minutes). DURATION: mean
      difference of -33 minutes 5 seconds +/- 31 minutes (95% CI -1 hour 35 minutes -
      29 minutes). There were 4 adverse events that did not require the patients to be
      withdrawn from the study. CONCLUSIONS: The anaesthetics in this study have very
      similar properties for use in surgery and have demonstrated a good safety and
      tolerability profile.

PMID- 22143692
TI  - The use of pedicled buccal fat pad combined with sequestrectomy  in
      bisphosphonate-related osteonecrosis of the maxilla.
AB  - The use of pedicled buccal fat pad flap (BFP) has proved of value for the closure
      of oroantral and oronasal communications and is a well-established tool in oral
      and maxillofacial surgery. Otherwise, the perceived limitations of surgical
      therapy for bisphosphonate-related osteonecrosis of the jaws (BRONJ) have been
      widely discussed, and recommendations have largely been made to offer aggressive
      surgery only to stage 3 patients refractary to conservative management. Oroantral
      communication may be a common complication after sequestrectomy and bone
      debridement in upper maxillary BRONJ. We report a case series of stage 3
      recalcitrant maxillary BRONJ surgically treated with extensive sequestrectomy and
      first reconstruction using pedicled BFP. All the cases presented an uneventful
      postoperative healing was uneventful without dehiscence, infection, necrosis or
      oroantral communication. We postulate that managing initially the site with BFP
      and primary closure may ensure a sufficient blood supply and adequate protection
      for an effective bone-healing response to occur. This technique may represent a
      mechanic protection and an abundant source of adipose-derived adult stem cells
      after debridement in upper maxillary BRONJ. We evaluate in this work results,
      advantages and indications of this technique.

PMID- 22143693
TI  - Determination of susceptibility to sensitization to dental materials in atopic
      and non-atopic patients.
AB  - INTRODUCTION: Some studies report that atopic patients have a greater frequency
      of delayed-type sensitization than non-atopic patients. OBJECTIVE: To determine
      the influence of the atopic condition on delayed sensitization to dental
      materials. DESIGN: cross-sectional study. METHODS: Forty (40) atopic subjects and
      forty (40) non-atopic subjects, of both sexes, between 20 and 65 years of age
      were included. The determination of delayed sensitization to dental materials was
      performed using patch test. An oral exam was also carried out to check for
      lesions of the oral mucosa. RESULTS: 61.25% of the patients were positive for
      delayed-type sensitization to one or more allergens, being palladium chloride
      (21.25%), ammoniated mercury (20%), benzoyl peroxide (12.5%) and amalgam (10%)
      the most frequent. The frequency of sensitization was 67.5% in the group of
      atopic patients, compared to 55% in the non atopic group (p>0.05). The materials
      with the greatest difference of sensitization in atopic compared to non-atopic
      patients were ammoniated mercury, benzoyl peroxide, amalgam and Bisphenol A
      Dimethacrylate (BIS-GMA). CONCLUSION: The atopic condition is not related to a
      higher frequency of delayed sensitization to a battery of dental materials.

PMID- 22143694
TI  - Low energy KTP laser in oral soft tissue surgery:  A 52 patients clinical study.
AB  - OBJECTIVES: Since 1962 laser appliances have been used for soft tissues surgery
      of oral cavity with significant advantages compared to the traditional
      instruments: excellent bleeding control, possibility to avoid the use of suture,
      good patient compliance thanks to a decrease of intra- and post-operative
      discomfort and biostimulating effect. Unfortunately, the wavelengths so far used
      have been seen to cause, in association with an excellent ablation capacity, heat
      damage of the tissues that can decrease healing process and cause a greater
      discomfort to patients. To evaluate the laser-assisted KTP laser surgery at low
      power in terms of characteristics of intervention and patients compliance. STUDY
      DESIGN: In this study, we describe the application of a new and recently
      introduced in dentistry wavelength, the KTP laser (532 nm), used with low power
      parameter (1 Watt - CW), evaluating the time of interventions and, by a Numerical
      Rating Scale, the intra and postoperative pain. RESULTS: KTP laser used at low
      power permits to obtain good pain control during operations that were carried out
      with only a topic anaesthetic (EMLA, Astratech), as shown in VAS tests. Good
      healing with limited or absent burning areas in treated portion of tissue.
      CONCLUSIONS: These preliminary study allows us to affirm that KTP laser with low
      parameters permits to perform oral surgery with good pain control and good wound
      healing. A greater number of clinical cases are however necessary to confirm the
      result obtained.

PMID- 22143695
TI  - Push-out bond strength of quartz fibre posts to root canal dentin using total
      etch and self-adhesive resin cements.
AB  - OBJECTIVES: Several adhesive systems are available for cementation of fibre posts
      into the root canal. The aim of the present study was to investigate the push-out
      bond strengths of quartz fibre posts to root dentin with the use of different
      total-etch and self-adhesive resin cements. STUDY DESIGN: Ninety single-rooted
      human premolars were endodontically treated and standardized post-spaces were
      prepared. Fibre posts were cemented with different luting agents: total-etch
      (Nexus NX3, Duo-Link, and RelyX ARC) and self-adhesive resin cements (Maxcem
      Elite, BisCem, and RelyX Unicem). Three post/dentin sections (coronal, middle and
      apical) were obtained from each specimen, and push-out bond strength test was
      performed in each section at a cross-head speed of 0.5 mm/min. Data was analyzed
      with two-factor and one-way analysis of variance and a post-hoc Tukey test at a
      significance level of p < 0.05. RESULTS: Cement type, canal region, and their
      interaction significantly influenced bond strength. Significantly higher bond
      strength values were observed in the apical region of self-adhesive cements. Only
      Duo-Link and RelyX ARC cements resulted in homogeneous bond strengths.
      CONCLUSIONS: Cementation of quartz fibre posts using self-adhesive cements
      provided higher push-out bond strengths especially in the apical region, while
      total-etch cements resulted in more uniform bond strengths in different regions
      of the root canal.

PMID- 22143696
TI  - Hydrodynamic ultrasonic maxillary sinus lift: review of a new technique and
      presentation of a clinical case.
AB  - OBJECTIVES: Placing implants in the posterior maxillary area has the drawback of
      working with scarce, poor quality bone in a significant percentage of cases.
      Numerous advanced surgical techniques have been developed to overcome the
      difficulties associated with these limitations. Subsequent to reports on the
      elevation of the maxillary sinus through the lateral approach, there were reports
      on the use of the crestal approach, which is less aggressive but requires a
      minimal amount of bone. Furthermore, it is more sensitive to operator technique,
      as the integrity of the sinus membrane is checked indirectly. The aim of this
      paper is to review the technical literature on minimally invasive sinus lift and
      compare the advantages of different techniques with IntraliftTM, a new technique.
      STUDY DESIGN: The present study is a review of techniques used to perform
      minimally invasive sinus lift published in Cochrane, Embase and Medline over the
      past ten years and the description of the crestal sinus lift technique based on
      minimally invasive piezosurgery, with the example of a case report. RESULTS: Only
      eight articles were found on minimally invasive techniques for sinus lift. The
      main advantage of this new technique, Intralift, is that it does not require a
      minimum amount of crestal bone (indeed, the smaller the width of the crestal
      bone, the better this technique is performed). The possibility of damage to the
      sinus membrane is minimised by using ultrasound based hydrodynamic pressure to
      lift it, while applying a very non-aggressive crestal approach. CONCLUSIONS: We
      believe that this technique is an advance in the search for less traumatic and
      aggressive techniques, which is the hallmark of current surgery.

PMID- 22143697
TI  - Tumors of the salivary gland in Mexicans.  A retrospective study of 360 cases.
AB  - OBJECTIVE: To establish distribution frequency and demographic characteristics of
      salivary gland tumours (SGT) in order to identify possible risk profiles. DESIGN
      OF STUDY: The present report constitutes an eight year retrospective study
      (January 2000-August 2007). The archives of the Clinical and Experimental
      Pathology Laboratory (Graduate and Research Division, Dental School, National
      Autonomous University of Mexico) as well as archives of the Surgical Pathology
      Service (General Hospital, Mexico City) were subject to revision in order to
      select all cases where SGT tumour diagnoses were emitted. Age and gender of
      patients as well as SGT topography were obtained from medical records. Selected
      cases were classified according to location of the lesion, histological lineage
      and biological behaviour. RESULTS: 360 cases of SGT were included, 227 (67%)
      cases were benign tumours, while 83 cases (23%) were malignant tumours. SGT were
      most frequent in women with ages ranging from their 3rd to 5th decades of life.
      275 tumours were located in major salivary glands, 78.9% of them were identified
      in the parotid gland. The most frequent location of tumours arising from minor
      salivary glands (33 cases, 38%) was found in the palatine glands. Tumours of
      epithelial lineage were the predominant histological type. The most frequent
      benign tumours were pleomorphic adenomas (86.1%) and papillary cystadenoma
      lymphomatosum (7.3%). The most frequent malignant tumours were adenoid cystic
      carcinomas (25%) and mucoepidermoid carcinomas (23.6%). CONCLUSIONS: Salivary
      gland tumours in Mexican population appear principally in major salivary glands
      of women in their 3rd to 5th decade of life.

PMID- 22143698
TI  - Diabetes mellitus, periapical inflammation and endodontic treatment outcome.
AB  - The possible connection between chronic oral inflammatory processes, such as
      apical periodontitis and periodontal disease (PD), and systemic health is one of
      the most interesting aspects faced by the medical and dental scientific
      community. Chronic apical periodontitis shares important characteristics with PD:
      1) both are chronic infections of the oral cavity, 2) the Gram-negative anaerobic
      microbiota found in both diseases is comparable, and 3) in both infectious
      processes increased local levels of inflammatory mediators may have an impact on
      systemic levels. One of the systemic disorders linked to PD is diabetes mellitus
      (DM); is therefore plausible to assume that chronic apical periodontitis and
      endodontic treatment are also associated with DM. The status of knowledge
      regarding the relationship between DM and endodontics is reviewed. Upon review,
      we conclude that there are data in the literature that associate DM with a higher
      prevalence of periapical lesions, greater size of the osteolityc lesions, greater
      likelihood of asymptomatic infections and worse prognosis for root filled teeth.
      The results of some studies suggest that periapical disease may contribute to
      diabetic metabolic dyscontrol.

PMID- 22143699
TI  - Evidence for transforming growth factor-beta 3 gene polymorphism in non-syndromic
      cleft lip and palate patients from Indian sub-continent.
AB  - OBJECTIVES: Orofacial clefts are major human birth defects with complex etiology.
      Previous studies have proposed Transforming growth factor - beta 3 (TGF-beta3)
      gene as a key player in contributing to non-syndromic cleft lip and palate,
      however none of the studies have yet included Indian population. Hence this study
      was designed to detect TGF-beta3 gene polymorphism in nonsyndromic cleft lip and
      palate patients from Indian population which is genetically distinct from
      previously studied populations. STUDY DESIGN: Peripheral blood samples of forty
      non-syndromic cleft lip and palate patients and forty unaffected individuals were
      collected for a case - control study design. Ethical clearance from the
      institutional review board and informed consent from all subjects was obtained.
      DNA extracted from the cases and controls was amplified using polymerase chain
      reaction (PCR) with TGF-beta3 specific primers. The obtained fragments were
      sequenced and TGF-beta3 gene polymorphisms were assessed based on the number of
      CA repeats. RESULTS: Chi -square test was used to compare the case and control
      groups. Results showed a significant difference in the number of CA repeats
      between the case and the control groups (p=0.01). CONCLUSION: This study confirms
      the crucial role of TGF-beta3 in the fusion of palatal shelves during development
      and further, provides novel evidence of TGF-beta3 gene polymorphism in the
      etiology of nonsyndromic cleft lip and palate in Indian subpopulation.

PMID- 22143700
TI  - Comparative study between manual injection intraosseous  anesthesia and
      conventional oral anesthesia.
AB  - OBJECTIVE: To compare intraosseous anesthesia (IA) with the conventional oral
      anesthesia techniques. MATERIAL AND METHOD: A simple-blind, prospective clinical
      study was carried out. Each patient underwent two anesthetic techniques:
      conventional (local infiltration and locoregional anesthetic block) and
      intraosseous, for respective dental operations. In order to allow comparison of
      IA versus conventional anesthesia, the two operations were similar and affected
      the same two teeth in opposite quadrants. RESULTS: A total of 200 oral anesthetic
      procedures were carried out in 100 patients. The mean patient age was 28.6+/-9.92
      years. Fifty-five vestibular infiltrations and 45 mandibular blocks were
      performed. All patients were also subjected to IA. The type of intervention
      (conservative or endodontic) exerted no significant influence (p=0.58 and p=0.62,
      respectively). The latency period was 8.52+/-2.44 minutes for the conventional
      techniques and 0.89+/-0.73 minutes for IA - the difference being statistically
      significant (p<0.05). Regarding patient anesthesia sensation, the infiltrative
      techniques lasted a maximum of one hour, the inferior alveolar nerve blocks
      lasted between 1-3 hours, and IA lasted only 2.5 minutes - the differences being
      statistically significant (p<=0.0000, Phi=0.29). Anesthetic success was recorded
      in 89% of the conventional procedures and in 78% of the IA. Most patients
      preferred IA (61%)(p=0.0032). CONCLUSIONS: The two anesthetic procedures have
      been compared for latency, duration of anesthetic effect, anesthetic success rate
      and patient preference. Intraosseous anesthesia has been shown to be a technique
      to be taken into account when planning conservative and endodontic treatments.

PMID- 22143701
TI  - A prospective clinical study of polycarboxylate  cement in periapical surgery.
AB  - OBJECTIVE: To evaluate the clinical efficacy of polycarboxylate cement as
      retrograde filling material. DESIGN: A prospective clinical study was made of 25
      patients subjected to periapical surgery with ultrasound and magnifying loupes,
      in which polycarboxylate cement was used as retrograde filling material.
      Measurements were made of the area and diameter of the lesions pre- and
      postoperatively, and 6 and 12 months after the operation. The apical resection
      and retrograde filling areas were also measured, and the prognosis following
      surgery was recorded. RESULTS: A total of 23 patients with 31 apicoectomized
      teeth were studied (2 patients being lost to follow-up). The mean area of the
      periapical lesions before surgery was 52.25 mm2, with a mean major diameter of
      6.1 mm and a mean lesser diameter of 4.8 mm. The success rate after 12 months was
      54.7%, according to the criteria of Von Arx and Kurt. The prognosis was poorer in
      females, in larger lesions, and in cases with larger retrograde filling areas.
      CONCLUSIONS: Polycarboxylate cement offers good results, with important bone
      regeneration after periapical surgery.

PMID- 22143702
TI  - Mechanical resistance of zirconium implant abutments: a review of the literature.
AB  - The increase of aesthetic demands, together with the successful outcome of
      current implants, has renewed interest in the search for new materials with
      enough mechanical properties and better aesthetic qualities than the materials
      customarily used in implanto-prosthetic rehabilitation. Among these materials,
      zirconium has been used in different types of implants, including prosthetic
      abutments. The aim of the present review is to analyse current scientific
      evidence supporting the use of this material for the above mentioned purposes. 
      We carried out the review of the literature published in the last ten years (2000
      through 2010) of in vitro trials of dynamic and static loading of zirconium
      abutments found in the databases of Medline and Cochrane using the key words
      zirconium abutment, fracture resistance, fracture strength, cyclic loading.
      Although we have found a wide variability of values among the different studies,
      abutments show favourable clinical behaviour for the rehabilitation of single
      implants in the anterior area. Such variability may be explained by the
      difficulty to simulate daily mastication under in vitro conditions. The clinical
      evidence, as found in our study, does not recommend the use of implanto
      prosthetic zirconium abutments in the molar area.

PMID- 22143703
TI  - Efficacy of different concentrations of sodium hypochlorite and  chlorhexidine in
      disinfection of contaminated Resilon cones.
AB  - OBJECTIVES: The aim of this study was to evaluate the effectiveness of different
      concentrations of Chlorhexidine (CHX) and sodium hypochlorite (NaOCl) in
      disinfecting contaminated Resilon cones within one minute. STUDY DESIGN: Fifty
      Resilon cones were divided into seven experimental groups and three control
      groups of 5 cones each. The cones of experimental groups were contaminated with
      E. faecalis and subsequently disinfected with different concentrations of NaOCl
      or CHX. The cones were then transferred into glass tubes containing
      thioglycollate media and incubated for 7 days. The tubes were examined for
      turbidity every 24 hours, and if bacterial growth occurred, samples were plated,
      incubated, gram stained and observed under microscope to confirm E. faecalis
      growth. Negative, positive, and washing control groups were also used. RESULTS:
      All the positive and washing control showed profound E.faecalis growth. All the
      cones disinfected with CHX showed bacterial growth; however, no E. faecalis
      growth occurred in any samples disinfected with NaOCl. CONCLUSION: Sodium
      hypochlorite, at concentrations of 0.5 to 5.25%, is an effective agent for
      disinfection of contaminated Resilon cones within one minute; however,
      chlorhexidine is unable to disinfect Resilon cones during one-minute exposure.

PMID- 22143704
TI  - Immediate implants following tooth extraction. A systematic review.
AB  - OBJECTIVES: The aim of this article is to review the current state of immediate
      implants, with their pros and contras, and the clinical indications and
      contraindications. MATERIAL AND METHODS: An exhaustive literature search has been
      carried out in the COCHRANE library and MEDLINE electronic databases from 2004 to
      November 2009. Randomized clinical trials and clinical trials focused on single
      implants placed in fresh extraction sockets were included and compared. A meta
      analysis could not be performed due to heterogeneity of the data. RESULTS: Twenty
      studies out of 135 articles from the initial search were finally included, which
      summed up a total of 1139 immediate implants with at least a 12-month follow-up.
      Our results have been compared with other current available papers in the
      literature reviewed that obtained similar outcomes. DISCUSSION: Immediate
      implants have predictable results with several advantages over delayed implant
      placement. However, technical complications have been described regarding this
      technique. Also, biomaterials may be needed when the jumping distance is greater
      than 1mm or any bone defect is present. CONCLUSIONS: Few studies report on
      success rates rather than survival rates in the literature reviewed. Short-term
      clinical results were described and results were comparable to those obtained
      with delayed implant placement. Further long-term, randomized clinical trials are
      needed to give scientific evidence on the benefits of immediate implants over
      delayed implant placement.

PMID- 22143705
TI  - Gene therapy with growth factors for periodontal tissue engineering--a review.
AB  - The treatment of oral and periodontal diseases and associated anomalies accounts
      for a significant proportion of the healthcare burden, with the manifestations of
      these conditions being functionally and psychologically debilitating. A challenge
      faced by periodontal therapy is the predictable regeneration of periodontal
      tissues lost as a consequence of disease. Growth factors are critical to the
      development, maturation, maintenance and repair of oral tissues as they establish
      an extra-cellular environment that is conducive to cell and tissue growth. Tissue
      engineering principles aim to exploit these properties in the development of
      biomimetic materials that can provide an appropriate microenvironment for tissue
      development. The aim of this paper is to review emerging periodontal therapies in
      the areas of materials science, growth factor biology and cell/gene therapy.
      Various such materials have been formulated into devices that can be used as
      vehicles for delivery of cells, growth factors and DNA. Different mechanisms of
      drug delivery are addressed in the context of novel approaches to reconstruct and
      engineer oral and tooth supporting structure.

PMID- 22143706
TI  - Effect of surface treatment with sandblasting and Er,Cr:YSGG laser on  bonding of
      stainless steel orthodontic brackets to silver amalgam.
AB  - OBJECTIVES: Satisfactory bonding of orthodontic attachments to amalgam is a
      challenge for orthodontists. The aim of this in vitro study was to compare the
      shear bond strength of stainless steel orthodontic brackets to silver amalgam
      treated with sandblasting and Er,Cr:YSGG laser. STUDY DESIGN: Fifty-four amalgam
      discs were prepared, polished and divided into three groups: In group 1 (the
      control group) the premolar brackets were bonded using Panavia F resin cement
      without any surface treatment; in groups 2 and 3, the specimens were subjected to
      sandblasting and Er,Cr:YSGG laser respectively, before bracket bonding. After
      immersing in distilled water at 37 degrees C for 24 hours, all the specimens were
      tested for shear bond strength. Bond failure sites were evaluated under a
      stereomicroscope. Data was analyzed using one-way ANOVA and a post hoc Tukey
      test. RESULTS: The highest and lowest shear bond strength values were recorded in
      the laser and control groups, respectively. There were significant differences in
      mean shear bond strength values between the laser and the other two groups
      (p<0.05). However, there were no significant differences between the sandblast
      and control groups (p=0.5). CONCLUSIONS: Amalgam surface treatment with
      Er,Cr:YSGG laser increased shear bond strength of stainless steel orthodontic
      brackets.

PMID- 22143707
TI  - Evaluation of enamel pearls by cone-beam computed tomography (CBCT).
AB  - OBJECTIVE: The aim of this study was to evaluate the frequency of enamel pearls
      according to population, sex and tooth groups on Cone-Beam Computed Tomography
      (CBCT) or Dental Volumetric Tomography (DVT) scans of patients, retrospectively.
      STUDY DESIGN: In this study, 15185 teeth belonging to 768 patients, 430 female
      and 338 male, was performed cross-sectional examination by CBCT. The volumetric
      Computed Tomography used in the study is Newton FP based on flat-panel. The data
      were analyzed with Pearson chi-squared test. RESULTS: Enamel pearls were detected
      in 36 subjects (4.69%). Of these enamel pearls, 19 were detected in male and 17
      were in male. There was no statistically a significant association between
      prevalence of enamel pearls and sex. All of enamel pearls were detected in molar
      teeth, for prevalence 0.83%. CONCLUSION: All of enamel pearls are found upper and
      lower molar teeth, especially the most commonly in maxillary second and third
      molars.

PMID- 22143708
TI  - A prospective, randomized, triple-blind comparison of articaine and bupivacaine
      for maxillary infiltrations.
AB  - OBJECTIVES: To compare the clinical anesthetic efficacy of 0.5% bupivacaine and
      4% articaine (both with 1:200.000 adrenaline) for anterior maxillary infiltration
      in healthy volunteers. MATERIAL AND METHODS: A triple-blind split-mouth
      randomized clinical trial was carried out in 20 volunteers. A supraperiosteal
      buccal injection of 0.9 ml of either solution at the apex of the lateral incisor
      was done in 2 appointments separated 2 weeks apart. The following outcome
      variables were measured: latency time, anesthetic efficacy (dental pulp,
      keratinized gingiva, alveolar mucosa and upper lip mucosa and tissue) and the
      duration of anesthetic effect. Hemodynamic parameters were monitored during the
      procedure. RESULTS: Latency time recorded was similar for both anesthetic
      solutions (p>0.05). No statistically significant differences were found in terms
      of anesthetic efficacy for dental pulp, keratinized gingiva or alveolar mucosa.
      Articaine had a significant higher proportion of successful anesthesia at 10
      minutes after infiltration in lip mucosa and lip skin (p=0.039). The duration of
      anesthesia was 336 minutes for bupivacaine and 167 minutes for articaine.
      (p<0.001). No significant hemodynamic alterations were noted during the
      procedure. CONCLUSIONS: Articaine and bupivacaine exhibited similar anesthetic
      efficacy for maxillary infiltrations. The duration of anesthesia was longer with
      the bupivacaine solution, but lip anesthesia was better with articaine.

PMID- 22143709
TI  - Malignant melanoma of the oral cavity. Review of the literature and experience in
      a Peruvian Population.
AB  - OBJECTIVE: To determine the epidemiological profile of malignant melanoma cases
      treated at the National Institute for Neoplastic Diseases "Dr. Eduardo Caceres
      Graziani" (INEN) over the period 1952 to 2008. STUDY DESIGN: All clinical records
      with complete data of patients presenting a histopathological diagnosis of
      malignant melanoma of the oral cavity were reviewed. Data such as age, gender,
      location, tumor size, disease length, presence of metastasis, treatment received
      and year of admission were recorded. RESULTS: During the study period 97 cases
      were found. The average age of patients was 52.85+/-1.6 years old mostly between
      50 and 59 years old; the predominant gender was the female. The most common
      location was the palate and there was 58.8% of cases with a tumor size bigger
      than or equal to 4 cm. The length of the disease in 38.1% of the cases was longer
      than a year and in great part of the cases (69.1%) there was no metastasis. The
      treatment of choice was the surgery plus radiotherapy in 38.1% of the cases.
      According to the admission date it was also noted that the number of cases is
      increasing. CONCLUSION: The results of this study demonstrate a late diagnosis
      and an increasing frequency of this neoplasia in the oral cavity.

PMID- 22143711
TI  - Evaluation of the agreement by examiners according to classifications of third
      molars.
AB  - OBJECTIVES: This study recorded and evaluated the intra- and inter-group
      agreement degree by different examiners for the classification of lower third
      molars according to both the Winter's and Pell & Gregory's systems. STUDY DESIGN:
      An observational and cross-sectional study was realized with forty lower third
      molars analyzed from twenty digital panoramic radiographs. Four examiner groups
      (undergraduates, maxillofacial surgeons, oral radiologists and clinical dentists)
      from Aracaju, Sergipe, Brazil, classified them in relation to angulation, class
      and position. The variance test (ANOVA) was applied in the examiner findings with
      significance level of p<0.05 and confidence intervals of 95%. RESULTS: Intra- and
      inter-group agreement was observed in Winter's classification system among all
      examiners. Pell & Gregory's classification system showed an average intra-group
      agreement and a statistical significant difference to position variable in inter
      group analysis with greater disagreement to the clinical dentists group (p<0.05).
      CONCLUSIONS: High reproducibility was associated to Winter's classification,
      whereas the system proposed by Pell & Gregory did not demonstrate appropriate
      levels of reliability.

PMID- 22143710
TI  - Pre-prosthetic surgical alterations in maxillectomy to enhance the prosthetic
      prognoses as part of rehabilitation of oral cancer patient.
AB  - OBJECTIVES: After maxillectomy, prosthetic restoration of the resulting defect is
      an essential step because it signals the beginning of patient's rehabilitation.
      The obturator used to restore the defect should be comfortable, restore adequate
      speech, deglutition, mastication, and be cosmetically acceptable, success will
      depend on the size and location of the defect and the quantity and integrity of
      the remaining structures, in addition to pre-prosthetic surgical preparation of
      defect site. Preoperative cooperation between the oncologist surgeon and the
      maxillofacial surgeon may allow obturation of a resultant defect by preservation
      of the premaxilla or the tuberosity on the defect side and maintaining the
      alveolar bone or teeth adjacent to the defect. This study evaluates the
      importance of pre-prosthetic surgical alterations at the time maxillectomy on the
      enhancement of the prosthetic prognoses as part of the rehabilitation of oral
      cancer patient. STUDY DESIGN: The study was carried out between 2003- 2008, on 66
      cancer patients(41 male-25 female) age ranged from 33 to 72 years, at National
      Cancer Institute, Cairo University, whom underwent maxillectomy surgery to remove
      malignant tumor as a part of cancer treatment. Patients were divided in two
      groups. Group A: Resection of maxilla followed by preprosthetic surgical
      preparation. Twenty-four cancer patients (13 male - 11 female). Group B:
      Resection of maxilla without any preprosthetic surgical preparation. Forty-two
      cancer patients (28 male-14 female). RESULTS: Outcome variables measured included
      facial contour and aesthetic results, speech understandability, ability to eat
      solid foods, oronasal separation, socializing outside the home, and return-to
      work status. Flap success and donor site morbidity were also studied.
      CONCLUSIONS: To improve the prosthetic restoration of maxillary defect resulting
      maxillary resection as part treatment of maxillofacial tumor depends on the close
      cooperation between prosthodontist and surgeon, by combination of pre-prosthetic
      surgery during maxillectomy and prosthodontic technique.

PMID- 22143712
TI  - Teething disturbances; prevalence of objective manifestations in  children under
      age 4 months to 36 months.
AB  - OBJECTIVE: The aim of this study was to present data as responded by parents on
      teething manifestation during eruption of primary teeth and the occurrence of
      objective manifestations in children ages 4 months to 36 months. SETTINGS AND
      DESIGN: Hospital based face-to-face questionnaire study. STUDY DESIGN: One
      thousand and one hundred children ages four to 36 months who had at least one
      erupting tooth were included in the study. Parents were asked to complete a short
      questionnaire and children were then checked by one of the authors. STATISTICAL
      ANALYSIS USED: Chi-square analysis was performed to analyze information obtained.
      Level of significance was set at P<.05. RESULTS: There were 660 girls (60%) and
      440 boys (40%) in the study. The most frequent clinical manifestations were:
      Fever (16%), drooling (12%), diarrhea (8%), fever-drooling (15%), fever
      diarrhea(8%) and drooling-diarrhea (6%). In the study sample, boys demonstrated a
      higher prevalence of diarrhea than girls (P<.05). No statistical significance
      regarding other clinical manifestations and gender were observed. Teething
      manifestations were most prevalent during the eruption of primary incisors.
      Occurrence of clinical manifestations in 4-12 months and 13-24 months age was
      statistically significant when compared with 25-36 months age (P<0.05).
      CONCLUSIONS: An association has been shown between general objective
      manifestations like fever (the most prevalent), drooling and diarrhea, and the
      eruption of primary teeth. Most manifestations appeared during the eruption of
      the primary incisors.

PMID- 22143713
TI  - Validation of the oral health impact profile (OHIP-20sp)  for Spanish edentulous
      patients.
AB  - OBJECTIVES: The purposes of this study are to validate the indicator of Oral
      Health Impact Profile for edentulous patients (OHIP-20sp) in the Spanish
      population and to analyze the factorial construct of the prosthetic well-being.
      STUDY DESIGN: [corrected] A total of twenty-one (n=21) edentulous patients
      wearing mandibular implant-overdentures on Locator(r) (LO) and twenty (n=20) with
      complete dentures (CD) were retrospectively evaluated in this study. All
      participants were recruited consecutively and were treated in the previous
      academic year 2009-2010 by professors of the University of Salamanca. Reliability
      analyses and validity tests were performed in order to evaluate the psychometric
      properties of OHIP-20sp employing two different total score methods (additional
      and simple count). A retrospective evaluation of the impact of the prosthetic
      treatment was captured with an evaluative instrument derived from OHIP-20, and
      named POST-OHIP-13. RESULTS: The reliability coefficient (Cronbach's alpha =
      0.91) has shown a high internal consistency. Item-total correlations coefficients
      ranged from 0.46 and 0.81. Five factors, named as disability, functional comfort,
      psychosocial impact, pain-discomfort and functional limitations were identified
      as principal components of the construct, explaining almost 85% of the variance.
      The 48% of the sample felt at least one impact in an occasional or more
      frequently manner (generally food packing). The global transition judgment of the
      prosthetic treatment using the POST-OHIP-13 was significantly higher in group LO
      than in the CD group. CONCLUSIONS: OHIP-20 seems to be a reliable and valid
      indicator to measure oral impact and satisfaction in the Spanish edentulous
      population. The underlying construct is comprised by 5 factors named as
      disability, functional comfort, psychosocial impact, pain-discomfort and
      functional limitations.

PMID- 22143714
TI  - Upper lip malignant neoplasms. A study of 59 cases.
AB  - OBJECTIVES: To present the demographic data, clinico-pathologic features and
      therapeutic outcome of a series of upper lip malignancies. STUDY DESIGN:
      Retrospective study at a single Cancer Institution in Mexico City during a 14
      year period. RESULTS: There were 59 cases, (30 males and 29 females); age range:
      14 to 106 years (mean: 73 yr.). Antecedents of ultraviolet light and tobacco
      exposure were found in 20 (33.9%) and 16 cases (27%) respectively. There were 35
      squamous cell carcinomas (59.3%), 19 basal cell carcinomas (32.2%) and one case
      each (1.7%) of adenocarcinoma NOS, adenoid cystic carcinoma, angiosarcoma, Merkel
      cell carcinoma and melanoma. There were 14 cases in stage I (23.7%), 14 in stage
      II (23.7%), 3 in stage III (5.1%) 14 in stage IV (23.7%) and 14 were not
      classified (23.7%). There were no significant differences with respect to the
      overall survival curve and the disease-free survival curve among surgical
      treatment and radiotherapy. In addition, there was not statistically significant
      difference in the overall survival and disease-free survival among squamous cell
      carcinoma and basal cell carcinoma cases with respect to the type of treatment.
      CONCLUSIONS: Upper lip malignant neoplasms are infrequent lesions. The present
      series describes the main clinico-pathological features in a hospital-based
      population in Mexico city and demonstrates some differences with respect to those
      found in the lower lip.

PMID- 22143715
TI  - Antibiotic prescription in the treatment of odontogenic infection by health
      professionals: a factor to consensus.
AB  - OBJECTIVE: To observe the attitude of dentists and family doctors in prescribing
      antibiotics for the treatment of dental infections. STUDY DESIGN: A poll was
      performed to determine the differences in the prescription of antibiotics for the
      treatment of odontogenic infection by dentists and family doctors of the primary
      care department of the Catalan Health Care Service. RESULTS: A hundred polls were
      distributed among family doctors, and another 100 ones among primary care
      dentists assigned to the Catalan Health Care Service of the Generalitat de
      Catalunya. Of the total of questionnaires distributed, 63 were retuned and
      answered from dentists and 71 from family doctors. Eighty-one percent of dentists
      included in the opinion poll considered amoxicillin as the first antibiotic
      choice for the treatment of odontogenic infections, while 73.2% of family doctors
      preferred the combination of amoxicillin and clavulanic acid. With regard to
      antibiotics of choice in patients allergic to penicillin, 67.7% of family doctors
      preferred macrolides (25.4% opted for clarithromycin, 25.4% for erythromycin and
      16.9% for spiramycin). However, clindamycin was the antibiotic most frequently
      prescribed by dentists (66.7%), followed by erythromycin (28.6%). CONCLUSIONS:
      The results of this study show a large discrepancy in the criteria for the
      treatment of odontogenic infections on the part of leading professionals involved
      in the management of this condition. Although the most common prescription
      involved beta-lactam antibiotics in both groups, several significant differences
      have been detected with regard to the second antibiotic choice.

PMID- 22143716
TI  - Side effects and complications of intraosseous  anesthesia and conventional oral
      anesthesia.
AB  - OBJECTIVE: To analyze the side effects and complications following intraosseous
      anesthesia (IA), comparing them with those of the conventional oral anesthesia
      techniques. MATERIAL AND METHOD: A simple-blind, prospective clinical study was
      carried out. Each patient underwent two anesthetic techniques: conventional
      (local infiltration and locoregional anesthetic block) and intraosseous, for
      respective dental operations. In order to allow comparison of IA versus
      conventional anesthesia, the two operations were similar and affected the same
      two teeth in opposite quadrants. Heart rate was recorded in all cases before
      injection of the anesthetic solution and again 30 seconds after injection. The
      complications observed after anesthetic administration were recorded. RESULTS: A
      total of 200 oral anesthetic procedures were carried out in 100 patients. Both IA
      and conventional anesthesia resulted in a significant increase in heart rate,
      though the increase was greater with the latter technique. Incidents were
      infrequent with either anesthetic technique, with no significant differences
      between them. Regarding the complications, there were significant differences in
      pain at the injection site, with more intense pain in the case of IA (x2=3.532,
      p=0.030, Phi2=0.02), while the limitation of oral aperture was more pronounced
      with conventional anesthesia (x2=5.128, p<0.05, Phi2=0.014). Post-anesthetic
      biting showed no significant differences (x2=4.082, p=0.121, Phi2=0.009).
      CONCLUSIONS: Both anesthetic techniques significantly increased heart rate, and
      IA caused comparatively more pain at the injection site, while limited oral
      aperture was more frequent with conventional anesthesia. Post-anesthetic biting
      showed no significant differences between the two techniques.

PMID- 22143717
TI  - Fracture resistance of roots filled with three  different obturation techniques.
AB  - OBJECTIVES: The aim of this study was to compare in vitro root fracture
      resistance following root canal filling with AH 26 using lateral condensation,
      BeeFill, and Thermafil techniques. STUDY DESIGN: Eighty extracted human
      mandibular premolars with similar dimensions were selected. In order to
      standardize the roots, measurements were taken in two separate regions of the
      teeth--at the cemento-enamel junction and 8 mm apically from the junction-
      buccolingual as well as mesiodistal for every tooth. Teeth were then randomly
      divided into five groups (n=16). With the exception of the non-prepared group
      (Group 1), instrumentation was done in all groups. In group 2, instrumentation
      but no filling was performed; in group 3, the obturation was done with AH 26 +
      gutta-percha; in group 4, with AH 26 + BeeFill and in group 5, AH 26 + a
      Thermafil obturator was used. All the roots were mounted vertically in copper
      rings and filled with acrylic resin, exposing 8 mm of the coronal part. A
      universal testing machine was used for the strength test. RESULTS: The results
      were analyzed using the one-way ANOVA test. The significance between the groups
      was tested with Temhane's T2 test. The results indicate that instrumentation of
      root canals had a significant effect on fracture resistance (p<0.05). In
      addition, there were no differences between the root canal obturation techniques;
      furthermore, these techniques did not create a statistically important resistance
      to vertical fracture (p>0.05). CONCLUSIONS: The results suggest that
      instrumentation of root canals significantly weakens the tooth structure to
      fracture and the root canal obturation techniques that are used are not able to
      form reinforcement.

PMID- 22143718
TI  - Characteristics of anatomical landmarks in the mandibular interforaminal region:
      a cone-beam computed tomography study.
AB  - OBJECTIVES: This study was conducted to assess appearance, visibility, location
      and course of anatomical landmarks in mandibular interforaminal region using cone
      beam computed tomography (CBCT). STUDY DESIGN: A total of 96 CBCT examinations
      was re-evaluated to exploit anatomical landmarks. The examinations used the
      Promax 3D CBCT unit. A sole examiner carried out all the measurements.
      Visibilities of the anatomical landmarks were scored using a four-point rating
      scale. RESULTS: The mandibular foramen, anterior loop, incisive canal and lingual
      foramen were observed in 100, 84, 83, 49% of the images, respectively. The mean
      size, diameter and width of anterior loop, incisive canal and lingual foramen
      were obtained 3.54 +/- 1.41, 1.47 +/- 0.50 and 0.8 +/- 0.09 mm, respectively.
      CONCLUSION: It is not safe to recommend any definite distance mesially from the
      mental foramen. The diameter of the canals and foramens should be determined on a
      case-by-case basis to exploit the appropriate location for each individual.

PMID- 22143719
TI  - Role of the dental surgeon in the early detection of adults with underlying HIV
      infection/AIDS.
AB  - A review is made of the late diagnosis of human immunodeficiency virus (HIV)
      infection, a subject of growing interest in public health. It has been estimated
      that in Europe 30% of all HIV-infected people are unaware of their seropositive
      condition, and this in turn is associated with a poorer long-term disease
      prognosis and an increased risk of transmission to other individuals. The role of
      the dental surgeon in this context could be of great importance, since there are
      many oral lesions that can suggest the existence of underlying infection. The
      study also addresses the controversial subject of rapid HIV testing, and whether
      these tests should be performed on a routine basis in the dental clinic, or
      whether it is preferable to refer the patient to a specialized center.

PMID- 22143720
TI  - An in vitro study showing the three-dimensional microenvironment influence over
      the behavior of head and neck squamous cell carcinoma.
AB  - OBJECTIVES: The Head and Neck Squamous Cell Carcinoma (HNSCC) ranks sixth
      worldwide. The mechanisms of growth, invasion and metastasis of this pathology
      are extensively studied and generally related to specific variations in signaling
      pathways like the PI3K-Akt; however most of these competent studies have been
      performed bidimensionally, which may hide important questions. This study sought
      to analyze the influence of the microenvironment upon the behavior of HNSCC.
      STUDY DESIGN: The status of pAkt, NF-kappaB and Cyclin D1 proteins was accessed
      through immunofluorescence and western blot methods in HNSCC cell lines
      originating from tongue, pharynx and metastatic lymph node when submitted to a
      three-dimensional culture model utilizing a matrix system. A bidimensional
      culture model (monolayer) was used as control. RESULTS: The HNSCC cell lines
      cultured three-dimensionally exhibited a growth pattern characterized by small
      isolated islands, different from the control group. When the three-dimensional
      model was applied, two of the studied cell lines showed the same expression
      pattern as the bidimensional model regarding nuclear or cytoplasmatic
      localization, as well as reduction of all protein levels; however, the cell line
      originated from tongue, which specially has the epidermal growth factor receptor
      constitutively activated, demonstrated nuclear translocation of pAkt and also an
      increase in the levels of Cyclin D1. CONCLUSIONS: The results suggest the
      influence of the microenvironment upon the behavior of HNSCC cells due to the
      changed expression of proteins related to tumor growth and cellular invasion.
      Furthermore, intrinsically genetic conditions also played important roles over
      the cells, despite the culture model employed.

PMID- 22143721
TI  - Perceived influence of oral health upon quality of life in heart transplant
      patients.
AB  - OBJECTIVE: A study was made of heart transplant patient perception of the
      influence of oral health upon quality of life, based on the Oral Health Impact
      Profile (OHIP-49) questionnaire validated for Spanish speaking subjects. DESIGN:
      A cross-sectional evaluation was made of the heart transplant patients followed
      up on in the Heart Transplantation Unit of Reina Sofia University Hospital
      (Spain), using the OHIP-49 questionnaire. The included patients were all over age
      18 and signed the corresponding informed consent to participation in the study.
      The data were entered in a database and analyzed using the SPSS statistical
      package. RESULTS: A total of 150 heart transplant patients (118 males and 32
      females, with a mean age of 54.94 years; range 19-79) were studied. The subjects
      showed a poor perceived influence of oral health upon quality of life, with a
      mean score of 24.43 out of a possible total of 196 points. Women showed
      significantly improved perception of the influence of oral health upon quality of
      life versus men. CONCLUSIONS: The subjects in our study showed a poor perceived
      influence of oral health upon quality of life.

PMID- 22143722
TI  - Intraosseous anesthesia with solution injection controlled by a computerized
      system versus conventional oral anesthesia: a preliminary study.
AB  - OBJECTIVE: To compare a computerized intraosseous anesthesia system with the
      conventional oral anesthesia techniques, and analyze the latency and duration of
      the anesthetic effect and patient preference. DESIGN: A simple-blind prospective
      study was made between March 2007 and May 2008. Each patient was subjected to two
      anesthetic techniques: conventional and intraosseous using the Quicksleeper(r)
      system (DHT, Cholet, France). A split-mouth design was adopted in which each
      patient underwent treatment of a tooth with one of the techniques, and treatment
      of the homologous contralateral tooth with the other technique. The treatments
      consisted of restorations, endodontic procedures and simple extractions. RESULTS:
      The study series comprised 12 females and 18 males with a mean age of 36.8 years.
      The 30 subjects underwent a total of 60 anesthetic procedures. Intraosseous and
      conventional oral anesthesia caused discomfort during administration in 46.3% and
      32.1% of the patients, respectively. The latency was 7.1+/-2.23 minutes for the
      conventional technique and 0.48+/-0.32 for intraosseous anesthesia--the
      difference being statistically significant. The depth of the anesthetic effect
      was sufficient to allow the patients to tolerate the dental treatments. The
      duration of the anesthetic effect in soft tissues was 199.3 minutes with the
      conventional technique versus only 1.6 minutes with intraosseous anesthesia--the
      difference between the two techniques being statistically significant. Most of
      the patients (69.7%) preferred intraosseous anesthesia. CONCLUSIONS: The
      described intraosseous anesthetic system is effective, with a much shorter
      latency than the conventional technique, sufficient duration of anesthesia to
      perform the required dental treatments, and with a much lesser soft tissue
      anesthetic effect. Most of the patients preferred intraosseous anesthesia.

PMID- 22143723
TI  - Class, type and position of 9148 surgically removed third molars in 3206
      patients: a retrospective study.
AB  - OBJECTIVE: To investigate the class, type, position, diagnosis and most common
      procedures used in the surgical removal of third molars, and evaluate the sex and
      age distribution in a representative sample of Mexican patients. STUDY DESIGN: A
      retrospective descriptive study was made covering the period 1993-2008 in
      relation to 9148 extracted third molars in 3206 patients treated in the Dental
      School of Salle Bajio University, A.C. (Mexico). Patients of either sex and aged
      11-59 years, with at least one third molar programmed for surgical removal, were
      included in the study. A descriptive statistical study was made. RESULTS: The
      mean patient age was 27.6 +/- 10.6 years. There were 2093 females (65.3%) and
      1111 males (34.6%). In relation to the 4025 upper molars, extraction was decided
      for prophylactic reasons in 3827 cases (95.08%). Type A presentations were
      recorded in 1929 cases (47.9%), with a vertical position in 1931 teeth (48%). In
      relation to the 5123 lower third molars, extraction was likewise most often
      indicated for prophylactic reasons (4424 cases, 86.36%). A total of 2353 teeth
      corresponded to type A (45.9%), 2545 were class I cases (49.7%), and a
      mesioangular position was observed in 1850 cases (36.1%). CONCLUSIONS: The
      present study shows that in Mexican patients, upper third molars most often
      correspond to type A and class I, with a vertical position, while lower third
      molars predominantly correspond to type A and class I, with a mesioangular
      position. This information can help dental surgeons take better decisions before
      and after surgery, to the benefit of their patients.

PMID- 22143724
TI  - In vitro antimicrobial activity of sodium hypochlorite, chlorhexidine gluconate
      and octenidine dihydrochloride in elimination of microorganisms within dentinal
      tubules of primary and permanent teeth.
AB  - The aim of this study was to evaluate the effectiveness of different irrigation
      solutions at different time intervals for the elimination of E. faecalis and C.
      albicans penetrated into the dentine tubules of primary and permanent teeth in
      vitro. The 4 mm primary and permanent teeth sections were sterilized and
      contaminated with a mixture of E. faecalis and C. albicans strains. After the
      application of different irrigation solutions (Sodium hypochlorite, Chlorhexidine
      gluconate, Octenidine Dihydrochloride, saline) to the contaminated tooth sections
      according to study groups, neutralizers were applied for inactivation of the
      solutions after 30 sec, 1 min and 5 min. Dentine shavings were placed into TSB
      and 10 uL from each tube was inoculated on agar plates, followed by an incubation
      period of 24 h at 37 degrees C. The colonies were counted macroscopically. The
      results were compared by using Kruskal-Wallis and Mann Whitney U tests, with a
      significance level at p<0.05. Among the irrigation solutions that were tested
      against E. faecalis on primary and permanent teeth, the most effective one was
      found as 5-minute application of 0.1% Octenidine Dihydrochloride. The
      antibacterial effects of the tested solutions on the same time periods against C.
      albicans revealed no significant difference. There were no statistically
      significant differences between primary and permanent teeth with respect to the
      antimicrobial activity of the tested solutions. Moreover, Octenidine
      Dihydrochloride may be used as an alternative endodontic irrigant.

PMID- 22143725
TI  - Comparison of the planimetry and point-counting methods for the assessment of the
      size of the mandible cysts on orthopantomograms.
AB  - OBJECTIVE: The purpose of this study is to compare the computer-assisted
      planimetry and point-counting methods in evaluating the sizes of the mandibular
      cysts with respect to their agreement and the time required to analyze. STUDY
      DESIGN: The surface areas of 46 mandibular cyst lesions on orthopantomograms were
      estimated using the point-counting and computer-assisted planimetry methods.
      Three observers evaluated the outlined areas twice, using the point-counting (PC)
      and computer-assisted planimetry (CAP) methods with an interval of two weeks. In
      the planimetry technique, digitalized images and ImageJ software were used to
      measure the surface area of the half mandibles and cysts. The grids were
      superimposed over the same images and the number of points hitting the interested
      structures was counted for the point-counting technique. The projection area
      fraction (PAF) of the cysts within the mandible was estimated using the obtained
      values by means of the two techniques. Intraclass correlation coefficient was
      used to assess the level of agreement between the two methods. Inter-rater
      reliability analysis using the Kappa statistic was performed to determine
      consistency among raters. RESULTS: CAP and PC techniques showed consistent intra
      observer values in all observers. Intraclass correlation between CAP and PC
      measurements of first, second and third observers were found to be 0.9986, 0.9988
      and 0.9994 respectively. The durations of PC technique was 32% higher than the
      CAP technique. CONCLUSION: PC and CAP methods were seemed to show sufficient
      agreement to be used interchangeably. The main disadvantage of the PC analysis is
      it takes more time than CAP method.

PMID- 22143726
TI  - Oral manifestations in a group of adults with autism spectrum disorder.
AB  - OBJECTIVE: A number of studies have evaluated the buccodental health of patients
      with autism spectrum disorder (ASD), though most have involved children, and no
      specific oral manifestations have been described. The present study describes the
      buccodental disorders and hygiene habits in a group of adults with ASD. STUDY
      DESIGN: A prospective case-control study was made of a group of patients with ASD
      (n=30), with a mean age of 27.7+/-5.69 years, and of a healthy age- and gender
      matched control group (n=30). An evaluation was made of the medical history,
      medication, oral hygiene habits and oral diseases, with determination of the
      CAOD, CAOS and OHI-S oral hygiene scores. RESULTS: Most of the patients in the
      ASD group used two or more drugs and were assisted in brushing 2-3 times a day.
      The most frequent manifestations were bruxism, self-inflicted oral lesions and
      certain malocclusions. The CAOD and CAOS scores were significantly lower than in
      the controls. CONCLUSIONS: Adults with ASD and assisted dental hygiene presented
      fewer caries than the non-disabled population. However, bruxism, ogival palate
      and anterior open bite were frequent in the patients with ASD.

PMID- 22143727
TI  - Clinical course of patients with episodic cluster headache treated with
      corticosteroids inproximity to the sphenopalatine ganglion: a preliminary study
      of 23 patients.
AB  - OBJECTIVE: A study is made of the clinical course of patients with episodic
      cluster headache following the injection of corticosteroids in the proximity of
      the sphenopalatine ganglion of the affected side. STUDY DESIGN: A retrospective
      observation study was made corresponding to the period between 2006 and 2010.
      Patients with episodic cluster headache received corticosteroid infiltrations in
      the vicinity of the sphenopalatine ganglion. Data were collected to assess the
      clinical course, quantifying pain intensity and quality of life. A total of 23
      patients (11 women and 12 men) with a mean age of 50.4 years (range 25-65) were
      included. Forty percent of the patients had undergone dental extractions in the
      quadrant affected by the pain, before the development of episodic cluster
      headache, and 37.8% underwent extractions in the same quadrant after appearance
      of the headache. RESULTS: Most of the patients suffered 1-3 attacks a day, with a
      duration of pain of between 31-90 minutes. The mean pain intensity score during
      the attacks at the time of the first visit was 8.8 (range 6-10), versus 5.4
      (range 3-9) one week after the first corticosteroid injection. On the first
      visit, 86.9% of the patients reported unbearable pain, versus 21.7% after one
      week, and a single patient after one month. CONCLUSIONS: The evolution of
      episodic cluster headache is unpredictable and variable, though corticosteroid
      administration clearly reduces the attacks and their duration.

PMID- 22143728
TI  - In vitro Enterococcus faecalis biofilm formation on five adhesive systems.
AB  - OBJECTIVE: To determine the E. faecalis biofilm formation on the surface of five
      adhesive systems (AS) and its relationship with roughness. STUDY DESIGN: The
      formation of E. faecalis biofilms was tested on the surface of four dual-cure AS:
      AdheSE DC, Clearfil DC Bond, Futurabond DC and Excite DSC and one light-cure
      antimicrobial AS, Clearfil Protect Bond, after 24 hours of incubation, using the
      MBEC high-throughput device. RESULTS: E. faecalis biofilms grew on all the
      adhesives. The least growth of biofilm was on Excite DSC, Clearfil Protect Bond,
      and the control. Futurabond DC resulted in the greatest roughness and biofilm
      amount. There was a close relationship between the quantity of biofilm and
      roughness, except for Clearfil Protect Bond, which showed little biofilm but high
      roughness. CONCLUSION: None of the tested AS prevented E. faecalis biofilm
      formation, although the least quantity was found on the surface of Clearfil
      Protect Bond.

PMID- 22143729
TI  - The efficacy of two rotary NiTi instruments and H-files  to remove gutta-percha
      from root canals.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of R-Endo(r) and
      K3(r) rotary nickel-titanium instruments compared with manual instrumentation
      with H-files, with use of a solvent, for removal of gutta-percha during
      retreatment. STUDY DESIGN: Forty five freshly extracted human single-rooted
      teeth, each with one root canal, were instrumented with K-files and filled using
      cold lateral compaction of gutta-percha and AH 26(r) sealer. The teeth were
      randomly divided into three groups of 15 specimens each. Removal of gutta-percha
      was performed with the following devices and techniques: Group 1 (H-files), Group
      2 (R-Endo(r)), and Group 3 (K3(r)). The specimens were rendered transparent for
      the evaluation of the area of remaining gutta-percha/sealer in buccolingual and
      mesiodistal directions. Statistical analysis as performed by using one-way ANOVA
      and Kruskal-Wallis tests (p=0.05). RESULTS: All retreatment techniques used in
      this study left some filling material inside the root canal. Images in
      buccolingual and mesiodistal directions showed no significant differences between
      the groups (p>0.05). CONCLUSIONS: Under the experimental conditions, the
      remaining filling material after retreatment was similar for each group.

PMID- 22143730
TI  - Study of serum CTX in 50 oral surgical patients treated with oral
      bisphosphonates.
AB  - OBJECTIVES: To determine whether there is a relationship between the total BP
      dose administered and the variations in serum CTX concentration. STUDY DESIGN:
      The study included 50 patients requiring dental implant surgery and treated with
      oral BPs, seen in an Oral Surgery and Implantology Unit between January 2007 and
      June 2009. The patients were divided into two groups: those in which the
      medication was not suspended before obtaining the laboratory test sample, and
      those patients referred from other dental clinics in which BPs was suspended
      before reporting to our Unit. The total drug dosage administered and the total
      dose per kilogram body weight were evaluated for comparison with serum CTX. The
      data obtained were correlated to the osteonecrosis risk table developed by Marx
      et al. in 2007. RESULTS: There were no significant differences between the two
      groups in relation to the total administered dose and the dose in mg/kg b.w.
      Likewise, in both groups no relationship was observed between the serum CTX value
      and the total administered dose or the dose in mg/kg b.w. No differences were
      found between the two patient groups regarding chemical osteonecrosis risk based
      on the criteria of Marx et al. CONCLUSIONS: No relationship was observed between
      the oral BP dose administered (total dose or expressed in mg/kg b.w.) and serum
      CTX concentration, and suspension of the medication did not influence the serum
      CTX levels.

PMID- 22143731
TI  - External apical root resorption in maxillary root-filled incisors after
      orthodontic treatment: a split-mouth design study.
AB  - INTRODUCTION: The purpose of this study was to compare, in a split mouth design,
      the external apical root resorption (EARR) associated with orthodontic treatment
      in root-filled maxillary incisors and their contralateral teeth with vital pulps.
      METHODOLOGY: The study sample consisted of 38 patients (14 males and 24 females),
      who had one root-filled incisor before completion of multiband/bracket
      orthodontic therapy for at least 1 year. For each patient, digital panoramic
      radiographs taken before and after orthodontic treatment were used to determine
      the root resortion and the proportion of external root resorption (PRR), defined
      as the ratio between the root resorption in the endodontically treated incisor
      and that in its contralateral incisor with a vital pulp. The student's t-test,
      chi-square test and logistic regression analysis were used to determine
      statistical significance. RESULTS: There was no statistically significant
      difference (p > 0.05) between EARR in vital teeth (1.1 +/- 1.0 mm) and
      endodontically treated incisors (1.1 +/- 0.8 mm). Twenty-six patients (68.4%)
      showed greater resorption of the endodontically treated incisor than its homolog
      vital tooth (p > 0.05). The mean and standard deviation of PPR were 1.0 +/- 0.2.
      Multivariate logistic regression suggested that PRR does not correlate with any
      of the variables analyzed. CONCLUSIONS: There was no significant difference in
      the amount or severity of external root resorption during orthodontic movement
      between root-filled incisors and their contralateral teeth with vital pulps.

PMID- 22143732
TI  - Primary oral melanoma: a histopathological and immunohistochemical study of 22
      cases of Latin America.
AB  - OBJECTIVE: The aim of this study was to analyze the histopathological and
      immunohistochemical characteristics of 22 cases of primary oral melanomas (OM).
      STUDY DESIGN: Twenty two cases of primary oral melanoma were analyzed by
      description of their histopathological features and immunohistochemical study
      using the antibodies S-100, HMB-45, Melan-A and Ki-67. RESULTS: The mean age was
      58 years and 14 cases were female. The main affected sites were the hard palate,
      followed by the upper gingiva. Microscopically, 15 cases presented level III of
      invasion, 2 cases were amelanotic and 13 showed a mixed epithelioid and
      plasmacytoid or spindle cells composition. Some cases showed necrosis,
      perivascular and perineural invasion. S-100 and HMB-45 were positive in all
      cases, but 3 cases were negative for Melan-A. The proliferative index with Ki-67
      was high, with labeling index ranging from 15.51% to 63% of positive cells.
      CONCLUSION: S-100 and HMB-45 are more frequently expressed than Melan-A in
      primary oral melanomas and these markers are helpful to confirm the diagnosis.

PMID- 22143733
TI  - Horizontal transmission of Streptococcus mutans in schoolchildren.
AB  - OBJECTIVE: The aim of this study was to analyze possible horizontal transmission
      patterns of S. mutans among 6-7-yr-old schoolchildren from the same class,
      identifying genotypes and their diversity and relationship with caries disease
      status. STUDY DESIGN: Caries indexes and saliva mutans streptococci and
      lactobacilli counts were recorded in 42 schoolchildren. Mutans streptococci
      colonies were identified by means of biochemical tests and all S. mutans strains
      were genotyped by arbitrarily primed polymerase chain reaction. A child was
      considered free of S. mutans when it could not be isolated in 3 samples at 1-week
      intervals. RESULTS: S. mutans was isolated in 30 schoolchildren: 20 having one
      genotype and 10 two genotypes. Higher mutans streptococci and caries index values
      were found in those with two genotypes. Five genotypes were isolated in more than
      1 schoolchild and one of these was isolated in 3 schoolchildren. Our results
      suggest that horizontal transmission may take place. CONCLUSION: Schoolchildren
      aged 6-7 yrs may be the source of mutual transmission of S. mutans.

PMID- 22143734
TI  - A double blind controlled trial comparing three treatment  modalities for dentin
      hypersensitivity.
AB  - AIM: This randomized, double blind, split mouth study was aimed to compare three
      dentin desensitizing treatment modalities. METHODS: Two hundred sixty teeth of 25
      patients; each having at least 2 hypersensitive teeth in each quadrant, were
      included. Teeth were randomized to 4 groups: Group A treated with 2% NaF
      solution, Group B received GLUMA(r); an aqueous solution of Hydroxy-Ethyl
      Methacrylate and Glutarldehyde, (HEMA-G), Group C received iontophoresis with
      distilled water (placebo) and Group D was treated with NaF-iontophoresis. Pain
      response was evaluated on a visual analogue scale (VAS), by using tactile, air
      blast and cold-water stimuli at 0-day, 15-day, 1-month and 3-months interval.
      RESULTS: All treatments were effective in reducing dentinal hypersensitivity
      significantly, Group D and Group B were more effective than Group A and Group C
      at all time intervals. Group D and Group B were equally effective in reducing
      dentinal hypersensitivity at 15-day and 1-month interval but Group D was more
      effective at 3-months. CONCLUSION: All treatment modalities were more effective
      in reducing hypersensitivity than placebo. 2% NaF-iontophoresis and HEMA-G were
      more effective than 2% NaF local application at all time intervals. But at 3
      months, 2% NaF-iontophoresis was more effective than HEMA-G, while placebo
      produced no significant effect in reduction of hypersensitivity.

PMID- 22143735
TI  - Osteotomy in direct sinus lift. A comparative study of the rotary technique and
      ultrasound.
AB  - PURPOSE: The present study investigates sinus membrane rupture in direct
      maxillary sinus lift with the rotary technique and with ultrasound, examining the
      survival of implants placed after sinus augmentation, and analyzing the bone gain
      obtained after the operation and 12 months after placement of the prosthetic
      restoration. MATERIALS AND METHODS: A retrospective study was made of 45 patients
      requiring maxillary sinus lift or augmentation for implant-prosthetic
      rehabilitation. Use was made of the handpiece and ostectomy drills for the rotary
      technique, and of specific tips for ultrasound. The implant success criteria were
      based on those developed by Buser. The bone gain obtained as a result of sinus
      lift was calculated from the postoperative panoramic X-rays. RESULTS: A total of
      57 direct elevations of the maxillary sinus were carried out: 32 with the rotary
      technique and 25 with ultrasound. Perforations of Schneider's membrane with the
      rotary technique and ultrasound occurred in 7% and 1.7% of the cases,
      respectively, with membrane integrity being preserved in 91.2%. Of the 100
      implants placed, 5 failed after one year of follow-up in the rotary technique
      group, while one implant failed in the ultrasound group. The rotary technique in
      turn afforded a bone gain of 5.9 mm, versus 6.7 mm with ultrasound. CONCLUSIONS:
      Perforations of the membrane sinusal in direct lift were more frequent with the
      rotary technique (7%) than with ultrasound (1.7%). Implant survival and bone gain
      were both greater when ultrasound was used.

PMID- 22143736
TI  - Characteristics of 351 supernumerary molar teeth in Turkish population.
AB  - OBJECTIVE: The aim of the present study was to evaluate the demographic profile
      of supernumerary molar (SM) teeth in people in various regions of Turkey. STUDY
      DESIGN: A retrospective analysis was carried out on an initial sample of 104,902
      subjects drawn from the ortopantographics files from 10 clinics in 7 Turkish
      cities with documentation of demographic data, the presence of SM teeth, their
      location, eruption, morphology, and position within the arch. In one region
      associated patho-logies and treatments were also evaluated. RESULTS: Three
      hundred fifty-one SMs were detected in 288 patients, constituting 0.33% of the
      study subjects, with a greater frequency in females (56.4%). SMs were found more
      frequently in the maxilla (87.7%) than in the mandible, and distomolars (62.9%)
      were more common than paramolars. The SMs encountered were mostly of conical
      shape (45.7%), impacted (81.1%), and in a vertical position (52.1). The 33% of SM
      teeth were related to impacted molar teeth. CONCLUSION: The most common
      complication involving these teeth was soft tissue irritation. Demographic data
      from such specific extensive studies are crucial for improved diagnosis of SM
      teeth. Early detection allows for measures against complications and more
      successful therapy.

PMID- 22143737
TI  - Fungiform papillae density in patients with burning mouth syndrome and
      xerostomia.
AB  - OBJECTIVE: The aim of this study was to analyze fungiform papillae density in
      patients with burning mouth syndrome (BMS) and xerostomia. STUDY DESIGN: In this
      cross-sectional clinical study, sixty patients were included (20 with BMS, 20
      with xerostomia and 20 healthy controls). The fungiform papillae density was
      analyzed over a small region on the anterior tip of the tongue with the aid of a
      digital camera. The number of papillae was measured in an area of 19 mm2.
      RESULTS: The patients with BMS showed significantly higher fungiform papillae
      density than the patients with xerostomia; though no statistically significant
      differences were recorded versus the control group. In the BMS group, 65% of all
      cases presented a density of 71-90 papillae (within an area of 19 mm2), while 10%
      had more than 90 papillae. On the contrary, 70% of the patients with xerostomia
      had fewer than 70 papillae in the studied area. CONCLUSIONS: The digital camera
      offers a rapid, noninvasive and relatively simple way to study fungiform papillae
      density. The patients with BMS have higher fungiform papillae density than the
      patients with xerostomia.

PMID- 22143738
TI  - Review of ultrasonic irrigation in endodontics:  increasing action of irrigating
      solutions.
AB  - INTRODUCTION: Effective irrigant delivery and agitation are prerequisites for
      successful endodontic treatment. Ultrasonic irrigation can be performed with or
      without simultaneous ultrasonic instrumentation. Existing literature reveals that
      ultrasonic irrigation may have a very positive effect on chemical, biological and
      physical debridement of the root canal system as investigated in many in vitro
      studies. OBJECTIVE: The purpose of this review article was to summarize and
      discuss the available information concerning ultrasonic irrigation in
      endodontics. METHODS: This article presents an overview of ultrasonic irrigation
      methods and their debridement efficacy. In this paper the relevant literature on
      passive ultrasonic irrigation is reviewed. Information from original scientific
      papers or reviews listed in MEDLINE and Cochrane were included in the review.
      RESULTS: The use of ultrasound in the irrigation procedure results in improved
      canal cleanliness, better irrigant transfer to the canal system, soft tissue
      debridement, and removal of smear layers and bacteria. There are many in vitro
      studies, but there is a need to standardize protocols, and correlate the clinical
      efficacy of ultrasonic devices with improved treatment outcomes. Understanding
      the basis of ultrasonic irrigation is fundamental for clinicians and researchers
      to improve the design and use of ultrasonic irrigation.

PMID- 22143739
TI  - Bupivacaine 0.5% versus articaine 4% for the removal of lower third molars. A
      crossover randomized controlled trial.
AB  - OBJECTIVE: To compare the anesthetic action of 0.5% bupivacaine in relation to 4%
      articaine, both with 1:200,000 epinephrine, in the surgical removal of lower
      third molars. As a secondary objective hemodynamic changes using both anesthetics
      were analyzed. STUDY DESIGN: Triple-blind crossover randomized clinical trial.
      Eighteen patients underwent bilateral removal of impacted lower third molars
      using 0.5% bupivacaine or 4% articaine in two different appointments.
      Preoperative, intraoperative and postoperative variables were recorded.
      Differences were assessed with McNemar tests and repeated measures ANOVA tests.
      RESULTS: Both solutions exhibited similar latency times and intraoperative
      efficacy. Statistical significant lower pain levels were observed with
      bupivacaine between the fifth (p=0.011) and the ninth (p=0.007) postoperative
      hours. Bupivacaine provided significantly longer lasting soft tissue anesthesia
      (p<0.5). Systolic blood pressure and heart rate values were significantly higher
      with articaine. CONCLUSIONS: Bupivacaine could be a valid alternative to
      articaine especially due to its early postoperative pain prevention ability.

PMID- 22143740
TI  - Odontogenic tumors: a retrospective study of four Brazilian diagnostic pathology
      centers.
AB  - OBJECTIVE: This article presents the results of a retrospective study of the
      frequency and classification of odontogenic tumors recorded at four centers of
      diagnostic pathology in Rio de Janeiro, Brazil. STUDY DESIGN: All medical records
      and microscopic slides of odontogenic tumor specimens for the years 1997 to 2007
      were retrieved from the files of four services of diagnostic pathology in Rio de
      Janeiro City. Diagnoses were re-evaluated and the tumors classified according to
      the latest (2005) World Health Organization Classification of Tumors. RESULTS: A
      total of 201 odontogenic tumors were found among 15,758 oral biopsies (1.3%). The
      frequencies of these tumors at the four centers ranged from 0.5% at the National
      Cancer Institute to 3.3% in a private laboratory. Chi-square analysis revealed
      statistically significant differences (p<0.05) between the proportions of
      odontogenic tumors in the studied centers. Of these, 94.5% were benign and 5.5%
      were malignant. Keratocystic odontogenic tumor (32.3%) was the most frequent
      lesion, followed by ameloblastoma (29.8%) and odontoma (18.4%). CONCLUSIONS:
      Odontogenic tumors are uncommon in Brazil. Different pathology laboratories
      reported divergent frequencies of odontogenic tumors, which may reflect
      institutional specializations and the patient populations served.

PMID- 22143741
TI  - Long-term stability of surgical-orthodontic correction of class III malocclusions
      with long-face syndrome.
AB  - OBJECTIVES: In the first place, to evaluate skeletal changes of the maxilla and
      mandible induced by surgical-orthodontic correction of malocclusions class III
      with long-face syndrome and secondly, to analyze the stability of these skeletal
      changes in the long term (more than 6 years). DESIGN OF STUDY: A retrospective,
      unicentric and longitudinal study of 19 patients who had undergone surgical and
      orthodontic therapy for class III skeletal malocclusion with long-face syndrome
      was undertaken. A cephalometric analysis based on 8 angle measurements, and
      statistical analyses at three different points in time (before orthodontic
      treatment, after orthognathic surgery and after a retention period of at least 6
      years) were carried out. RESULTS: The changes produced following surgery show
      that, with the exception of the maxillary plane and the facial axis, all other
      variables presented changes of great statistical difference. CONCLUSIONS:
      Skeletal changes after orthodontic-surgical correction present maxillary advance,
      mandibular regression and mandibular anterorotation. The angles that represent
      the mandibular vertical position (ramus angle, goniac angle and mandibular plane
      angle) showed statistically significant relapses and no stability in contrast to
      the facial axis.

PMID- 22143742
TI  - Utility of the social communication questionnaire-current and social
      responsiveness scale as teacher-report screening tools for autism spectrum
      disorders.
AB  - Limited research exists regarding the role of teachers in screening for Autism
      Spectrum Disorders (ASD). The current study examined the use of the Social
      Communication Questionnaire (SCQ) and Social Responsiveness Scale (SRS) as
      completed by parents and teachers about school-age children from the Simons
      Simplex Collection. Using the recommended cutoff scores in the manuals and extant
      literature, the teacher-completed SCQ and SRS yielded lower sensitivity and
      specificity values than would be desirable; however, lowering the cutoff scores
      on both instruments improved sensitivity and specificity to more adequate levels
      for screening purposes. Using the adjusted cutoff scores, the SRS teacher form
      appears to be a slightly better screener than the SCQ. Implications and
      limitations are discussed, as well as areas for future research.

PMID- 22143743
TI  - HS-SPME-GC*GC-qMS volatile metabolite profiling of Chrysolina herbacea frass and
      Mentha spp. leaves.
AB  - Headspace solid-phase microextraction (HS-SPME) comprehensive two-dimensional
      (2D) gas chromatography combined with quadrupole-mass spectrometry (GC*GC-qMS)
      with dedicated comparative data elaboration was applied to separate chemical
      patterns arising from the interaction between some Mentha species and the
      herbivore Chrysolina herbacea, also known as the mint bug. Upon feeding on
      different Mentha species (Mentha spicata L., Mentha * piperita L. and Mentha
      longifolia L.), C. herbacea produced frass (faeces) which were characterized by a
      typical volatile fraction. HS-SPME GC*GC-qMS analysis of the complex volatile
      fraction of both mint leaf and C. herbacea frass was submitted to advanced
      fingerprinting analysis of 2D chromatographic data. 1,8-Cineole, found in the
      leaves of all the Mentha species examined, was oxidized, and C. herbacea frass
      yielded high rates of several hydroxy-1,8-cineoles, including 2alpha-hydroxy-,
      3alpha-hydroxy-, 3beta-hydroxy- and 9-hydroxy-1,8-cineole. Upon insect feeding,
      several unknown oxidized monoterpenes, a p-menthane diol and three unknown
      phenylpropanoids were also detected in the frass volatiles. In M. longifolia, the
      occurrence of the monoterpene piperitenone oxide was found to be toxic and
      associated with insect death. The results of this work show that high throughput
      techniques such as HS-SPME and GC*GC-qMS fingerprint analysis are ideal tools to
      analyze complex volatile matrices, and provide a sensitive method for the direct
      comparison and chemical visualization of plant and insect emitted volatile
      components.

PMID- 22143744
TI  - Surgical subinguinal approach to varicocele combined with antegrade
      intraoperative sclerosis of venous vessels.
AB  - Varicocele is treated by different surgical techniques, none of which is yet
      acknowledged as the "gold standard." Some of these techniques, especially
      microsurgical techniques, are very time consuming and thus expensive, and the
      treatment of varicocele still causes some complications and recurrences. Marmar
      and Kim's technique presents some indisputable advantages: it allows the
      preservation of the arteries and seems to offer the highest percentage of success
      and lowest number of complications. The authors modified and simplified the
      microsurgical technique of Marmar and Kim, using a subinguinal approach with
      intraoperative antegrade sclerotherapy of dilated veins. After the cord has been
      clamped, 1.5 to 3 mL of 3% aetoxisclerol mixed with 0.5 mL of air is injected.
      Commonly, minor complications can occur. The most common complication is
      transient penile lymphangitis, the cause of which is unclear. As the procedure
      allows selective sparing of the lymphatic vessels, it avoids hydrocele due to the
      performed procedure.

PMID- 22143745
TI  - Evaluation of soft tissue attachments to a novel intra-abdominal prosthetic in a
      rabbit model.
AB  - BACKGROUND: Laparoscopic ventral hernia repair requires placement of an
      intraperitoneal prosthetic. Composite mesh types have been developed to address
      the shortcomings of standard meshes. The authors evaluated the host reaction to
      intraperitoneal placement of a novel composite material. MATERIALS AND METHODS: A
      comparison of an innovative polypropylene/polylactide composite mesh was made to
      parietex composite (PCO), Proceed, and DualMesh. Eighteen meshes per group were
      implanted on intact peritoneum in New Zealand white rabbits. The main outcome
      measures included the formation of visceral adhesions, adhesion tenacity,
      tensiometric measurements, and histological analysis. Evaluations of adhesions
      were made at 1, 4, and 16 weeks using a 2-mm minilaparoscopy. RESULTS: There were
      no significant differences in the mean adhesion scores between the composite mesh
      types at week 1 (P = .15) and week 16 (P = .06). At 4 weeks, PCO had
      significantly fewer adhesions when compared with the other 3 mesh types (P =
      .02). Adhesion tenacity was also equivalent within the group at 16 weeks (P =
      .06). Tensiometry and histological analysis revealed no statistically significant
      differences between the mesh types. CONCLUSIONS: Four different composite mesh
      types had equivalent intra-abdominal soft tissue attachments in a rabbit model
      after a 16-week implantation period. PCO demonstrated the lowest mean adhesion
      score of each mesh type. Each mesh exhibited equivalent stiffness and energy to
      failure after explantation. The 4 composite mesh types demonstrated the
      successful formation of a neoperitoneum and comparable host biocompatibility as
      evidenced by similar degrees of inflammation.

PMID- 22143746
TI  - Fibrin glue with gentamicin as an alternative to conventional surgery in
      experimental treatment of duodenal fistula in rats.
AB  - Duodenal fistula is a significant ongoing surgical problem. Minimal invasive
      treatment might be an alternative to conventional open surgery. This study aimed
      to investigate whether addition of gentamicin to fibrin adhesive can augment
      current surgical methods. Having established a fistula, the defect was closed
      using the following: simple suturing, suturing covered with fibrin sealant only,
      or suturing with fibrin sealant mixed with gentamicin. Bursting pressure and
      macroscopic and microscopic examination were evaluated on the second and sixth
      day after surgery. The study demonstrated there was no significant difference in
      overall outcome between the 3 groups. However, on macroscopic examination, the
      mixture of antibiotic and fibrin adhesive decreased formation of adhesions and
      abscesses. Microscopically, there was decreased inflammation, improved
      granulation, and earlier onset of fibrin filament deposition, possibly leading to
      enhanced wound healing. The addition of gentamicin to fibrin sealant can be a
      useful adjunct to standard surgical closure in duodenal fistula management.

PMID- 22143747
TI  - Single-port laparoscopic intragastric surgery using SILS port: a feasibility
      study on a porcine model.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility, safety, and
      efficiency of single-port laparoscopic intragastric surgery by using a single
      port device. METHODS: The single-port device was introduced into the anterior
      wall of the stomach through 2.5-cm long abdominal and gastric incisions. Gastric
      mucosa resection and suturing (group 1) and mucosa resection by using staplers
      (group 2) were performed with 3 pigs in each group. RESULTS: The time for setting
      up the intragastric ports ranged from 8 to 40 minutes (average 16.2 +/- 12.2
      minutes). The total surgery times for the 3 pigs in group 1 were 75, 45, and 38
      minutes and for the other 3 pigs in group 2 were 80, 85, 70 minutes,
      respectively. CONCLUSION: A simple and stable intragastric surgery platform can
      be set up by using the single-port device placed into the stomach. This seems to
      be safe and feasible and may be a suitable alternative for humans.

PMID- 22143748
TI  - Durability of biologic implants for use in hernia repair: a review.
AB  - In the past 10 years, hernia repair has evolved from primarily using suture
      closure to using mesh repair. Synthetic mesh implants were the initial gold
      standard, but the rate of complications such as infection, adhesions, and erosion
      was higher with synthetics than has been observed with newer biologic implants.
      As efforts to develop the ideal implant continue, the advantages of biologics for
      hernia and other soft-tissue repair become increasingly apparent. Animal-sourced
      biologics have the potential advantage over human dermis of being more amenable
      to standardization, and porcine dermal collagen architecture closely resembles
      that of human dermis. Cross-linking the collagen adds strength and durability to
      the implant that facilitates healing of surgical wounds, just as endogenous
      collagen, which is cross-linked, has innate durability that enhances natural
      wound healing. This review defines and assesses durability of the acellular
      collagen (biologic) implant options available for hernia repair. The factors that
      affect wound healing-and hernia repair--are summarized. Additionally, the
      particular features that enhance durability are described, and durability-related
      clinical outcomes discussed in the literature are cited to aid clinicians in
      making informed surgical choices.

PMID- 22143749
TI  - An original endoluminal magnetic anastomotic device allowing pure NOTES
      transgastric and transrectal sigmoidectomy in a porcine model: proof of concept.
AB  - INTRODUCTION: While experimental natural orifice transluminal endoscopic surgery
      (NOTES) sigmoid colectomies have been reported, pure NOTES anastomoses are
      restricted by the limited reach of commercially available circular staplers.
      MAGNAMOSIS is a set of self-orienting magnetic rings that can be delivered
      endoluminally throughout the colon to generate a compression anastomosis. Aim. To
      assess the feasibility of a pure NOTES transrectal (TR) and transgastric (TG)
      approach to perform any segmental colectomy. MATERIALS AND METHODS: One pig (50
      kg) underwent the experimental procedure as follows: (a) creation of the TG
      access to the peritoneal cavity, (b) precise transluminal placement of the
      proximal MAGNAMOSIS ring, (c) creation of the TR access with the TEO and
      transrectal dissection of the sigmoid mesentery, (d) resection of the surgical
      specimen, (e) transrectal extraction of the specimen, (f) delivery and mating of
      the distal MAGNAMOSIS ring, and (g) closure of the TG and TR viscerotomies. The
      animal survived for 14 days at which time burst pressure and histology were
      performed. RESULTS: A pure NOTES TR and TG segmental colectomy was performed in
      139 minutes. The postoperative course was uneventful. The animal had a formed
      bowel movement including the magnetic rings on postoperative day 5. Endoscopic
      examination at postoperative day 14 revealed a patent anastomosis. Necropsy
      revealed no abscess or signs of peritonitis. Burst pressure was >198 mm Hg. The
      histology showed a sealed anastomosis with mild inflammation. CONCLUSIONS:
      MAGNAMOSIS enabled a totally NOTES partial colectomy with combined TG and TR
      access. The flexible delivery options and low cost of manufacturing could make
      MAGNAMOSIS an attractive alternative to circular staplers.

PMID- 22143750
TI  - Transvaginal NOTES hybrid cholecystectomy.
AB  - BACKGROUND: Initial reports confirm the safety and feasibility of natural orifice
      transluminal eendoscopic surgery (NOTES) transvaginal hybrid cholecystectomy
      (TVC). Benefits of TVC include no visible scars, less pain, and shorter recovery.
      The authors describe a single surgeon's initial experience with TVC through his
      first 20 cases. METHOD: Under direct visualization from a 5-mm umbilical trochar,
      a 12-mm trocar, or in 2 cases a SILS port was introduced through the posterior
      vagina into the cul-de-sac. The gallbladder was visualized using an endoscope
      introduced through the vaginal port. Using extracorporeal stay sutures for
      retraction, the cystic duct and artery were dissected free, clipped, and divided.
      The gallbladder was then removed through the vaginal port. RESULTS: Twenty
      patients underwent a successful TVC. The average age was 34.9 years (21-55
      years), average body mass index was 29.9 kg/m2 (18.3-38.1 kg/m2), and the mean
      operative time was 71.4 minutes (42-116 minutes). CONCLUSION: TVC is a safe,
      feasible, and attractive alternative to traditional 4-port laparoscopic
      cholecystectomy.

PMID- 22143751
TI  - Magnetic-assisted single-port sleeve gastrectomy.
AB  - BACKGROUND: Sleeve gastrectomy is a recent, purely restrictive procedure in
      bariatric surgery that has shown results similar to gastric bypass over the short
      and middle term. At the same time, single-port access surgery has fostered the
      development of new techniques and methods seeking better cosmetic results and
      less postoperative pain, while maintaining the satisfactory results obtained by
      the standard laparoscopic approach. One of the problems associated to single
      access surgery is the lack of traction and the difficulties to retract the liver.
      The authors' aim was to try to avoid additional trocars or sutures in order to
      perform pure single-incision surgery, using 2 magnetic forceps. METHODS: The
      authors present the case of a 51-year-old morbidly obese female (body mass index
      = 44.82) who underwent a pure single-access laparoscopic sleeve gastrectomy with
      no additional trocars or sutures and assisted by 2 neodymium magnetic forceps:
      one to retract the liver and the other to retract the stomach in order to provide
      sufficient triangulation for adequate exposure of the surgical field during
      dissection. RESULTS: The procedure was completed in 120 minutes. No preoperative
      or postoperative complications were recorded, and the patient was discharged 2
      days after surgery. CONCLUSION: Single-port access sleeve gastrectomy assisted by
      magnetic forceps is feasible and safe in the hands of experienced laparoscopic
      surgeons, solving one of the problems associated to this type of surgery, that
      is, the need for an additional trocar and needles or sutures to retract the liver
      and stomach in order to perform the operation.

PMID- 22143752
TI  - Surgent University: the establishment and evaluation of a national online
      clinical teaching repository for surgical trainees and students.
AB  - INTRODUCTION: The aim of this study was to develop a new teaching strategy for
      medical students while creating a national online repository system (Surgent
      University). Then, the potential of this e-learning modality to facilitate
      learning of clinical surgery was evaluated. METHODS: An online repository and
      Internet-based interface was designed and hosted on the medical education Web
      site, www.surgent.ie. Participation was by medical students across 3 Irish
      universities. Student use of the repository was quantitatively assessed over an 8
      week period. They were then invited to complete an anonymous survey assessing the
      effectiveness of the online repository. Statistical analysis was performed using
      SPSS version 15, with P < .05 considered significant. RESULTS: Over the study
      period, the online repository received 6105 uploaded facts by 182 final-year
      medical students from 3 different universities. The repository Web pages were
      accessed 54 061 times with 4609 individual searches of the repository. Of the 60
      participating students invited to provide survey-based feedback, there were 40
      respondents, giving a 66.7% response rate. Of those surveyed, 70% (n = 28) rated
      the online repository as highly beneficial and 75% (n = 30) as highly relevant.
      Overall, 87.5% (n = 35) felt that it should be continued, and 70% (n = 28) felt
      that it should be expanded beyond surgery to include other hospital specialties.
      Those finding the program interface user-friendly were more likely to find it
      beneficial (P = .031) and relevant to their ongoing education (P = .002).
      CONCLUSIONS: A user-friendly interface allows for high levels of usage, whereas a
      "student-centered" structure ensures that the facts uploaded are beneficial and
      relevant to medical students' education.

PMID- 22143753
TI  - Evaluation of porous starch as a flavour carrier.
AB  - A commercial porous starch was evaluated for the use as a carrier for liquid
      flavours. Encapsulation trials performed with diacetyl showed a high initial load
      and good retention over time when more polar solvents commonly used in flavour
      creation were used. The physical interactions between the porous starch and
      solvents used in flavour creation were also studied. The glass transition
      temperature of the starch decreased upon addition of the polar solvents, ethanol
      and propylene glycol. Propylene glycol also produced an exothermic peak when
      mixed with porous starch, possibly due to the formation of complexes between the
      two components. Low resolution (1)H-NMR results suggested that a stronger
      interaction was established between more polar solvents and the porous starch, as
      indicated by a more marked decrease in relaxation times and proton diffusion
      coefficient of the solvents on adding porous starch.

PMID- 22143754
TI  - Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to
      single-stranded telomeric-repeat DNA.
AB  - Telomerase copies its internal RNA template to synthesize telomeric DNA repeats.
      Unlike other polymerases, telomerase can retain its single-stranded product
      through multiple rounds of template dissociation and repositioning to accomplish
      repeat addition processivity (RAP). Tetrahymena telomerase holoenzyme RAP depends
      on a subunit, Teb1, with autonomous DNA-binding activity. Sequence homology and
      domain modeling suggest that Teb1 is a paralog of RPA70C, the largest subunit of
      the single-stranded DNA-binding factor replication protein (RPA), but unlike RPA,
      Teb1 binds DNA with high specificity for telomeric repeats. To understand the
      structural basis and significance of telomeric-repeat DNA recognition by Teb1, we
      solved crystal structures of three proposed Teb1 DNA-binding domains and defined
      amino acids of each domain that contribute to DNA interaction. Our studies
      indicate that two central Teb1 DNA-binding oligonucleotide/oligosaccharide
      binding-fold domains, Teb1A and Teb1B, achieve high affinity and selectivity of
      telomeric-repeat recognition by principles similar to the telomere end-capping
      protein POT1 (protection of telomeres 1). An additional C-terminal Teb1
      oligonucleotide/oligosaccharide-binding-fold domain, Teb1C, has features shared
      with the RPA70 C-terminal domain including a putative direct DNA-binding surface
      that is critical for high-RAP activity of reconstituted holoenzyme. The Teb1C
      zinc ribbon motif does not contribute to DNA binding but is nonetheless required
      for high-RAP activity, perhaps contributing to Teb1 physical association with the
      remainder of the holoenzyme. Our results suggest the biological model that high
      affinity DNA binding by Teb1AB recruits holoenzyme to telomeres and subsequent
      Teb1C-DNA association traps product in a sliding-clamp-like manner that does not
      require high-affinity DNA binding for high stability of enzyme-product
      association.

PMID- 22143756
TI  - On the recombination of hydronium and hydroxide ions in water.
AB  - The recombination of hydronium and hydroxide ions following water ionization is
      one of the most fundamental processes determining the pH of water. The
      neutralization step once the solvated ions are in close proximity is
      phenomenologically understood to be fast, but the molecular mechanism has not
      been directly probed by experiments. We elucidate the mechanism of recombination
      in liquid water with ab initio molecular dynamics simulations, and it emerges as
      quite different from the conventional view of the Grotthuss mechanism. The
      neutralization event involves a collective compression of the water-wire bridging
      the ions, which occurs in approximately 0.5 ps, triggering a concerted triple
      jump of the protons. This process leaves the neutralized hydroxide in a
      hypercoordinated state, with the implications that enhanced collective
      compressions of several water molecules around similarly hypercoordinated states
      are likely to serve as nucleation events for the autoionization of liquid water.

PMID- 22143755
TI  - Kinetic analysis reveals the ordered coupling of translation termination and
      ribosome recycling in yeast.
AB  - Although well defined in bacterial systems, the molecular mechanisms underlying
      ribosome recycling in eukaryotic cells have only begun to be explored. Recent
      studies have proposed a direct role for eukaryotic termination factors eRF1 and
      eRF3 (and the related factors Dom34 and Hbs1) in downstream recycling processes;
      however, our understanding of the connection between termination and recycling in
      eukaryotes is limited. Here, using an in vitro reconstituted yeast translation
      system, we identify a key role for the multifunctional ABC-family protein Rli1 in
      stimulating both eRF1-mediated termination and ribosome recycling in yeast.
      Through subsequent kinetic analysis, we uncover a network of regulatory features
      that provides mechanistic insight into how the events of termination and
      recycling are obligately ordered. These results establish a model in which
      eukaryotic termination and recycling are not clearly demarcated events, as they
      are in bacteria, but coupled stages of the same release-factor mediated process.

PMID- 22143757
TI  - Local adaptation of an introduced transgenic insect fungal pathogen due to new
      beneficial mutations.
AB  - Genetically modified Metarhizium spp represent a major new arsenal for combating
      insect pests and insect-borne diseases. However, for these tools to be used
      safely and effectively, we need a much better understanding of their evolutionary
      potential and invasion ecology. In order to model natural as well as
      anthropogenic dispersal scenarios, we investigated evolutionary processes in a
      green fluorescent protein tagged strain of Metarhizium robertsii following
      transfer from a semitropical to a temperate soil community. Adaptive changes
      occurred over four years despite recurrent genetic bottlenecks and lack of
      recombination with locally well adapted strains. By coupling microarray-based
      functional analysis with DNA hybridizations we determined that expression of cell
      wall and stress response genes evolved at an accelerated rate in multiple
      replicates, whereas virulence determinants, transposons, and chromosome structure
      were unaltered. The mutable genes were enriched for TATA boxes possibly because
      they are larger mutational targets. In further field trials, we showed that the
      new mutations increased the fitness of M. robertsii in the new range by enhancing
      saprophytic associations, and these benefits were maintained in subsequent years.
      Consistent with selection being habitat rather than host specific, populations of
      an avirulent mutant cycled with seasons similarly to the wild type, whereas a
      mutant unable to adhere to plant roots showed a linear decrease in population.
      Our results provide a mechanistic basis for understanding postrelease
      adaptations, show that agents can be selected that lack gene flow and virulence
      evolution, and describe a means of genetically containing transgenic strains by
      disrupting the Mad2 gene.

PMID- 22143758
TI  - Electronic dynamics and plasmons of sodium under compression.
AB  - Sodium, which has long been regarded as one of the simplest metals, displays a
      great deal of structural, optical, and electronic complexities under compression.
      We compressed pure Na in the body-centered cubic structure to 52 GPa and in the
      face-centered cubic structure from 64 to 97 GPa, and studied the plasmon
      excitations of both structures using the momentum-dependent inelastic X-ray
      scattering technique. The plasmon dispersion curves as a function of pressure
      were extrapolated to zero momentum with a quadratic approximation. As predicted
      by the simple free-electron model, the square of the zero-momentum plasmon energy
      increases linearly with densification of the body-centered cubic Na up to 1.5
      fold. At further compressions and in face-centered cubic Na above 64 GPa, the
      linear relation curves progressively toward the density axis up to 3.7-fold
      densification at 97 GPa. Ab initio calculations indicate that the deviation is an
      expected behavior of Na remaining a simple metal.

PMID- 22143759
TI  - Dynamic metabolic labeling of DNA in vivo with arabinosyl nucleosides.
AB  - Commonly used metabolic labels for DNA, including 5-ethynyl-2'-deoxyuridine (EdU)
      and BrdU, are toxic antimetabolites that cause DNA instability, necrosis, and
      cell-cycle arrest. In addition to perturbing biological function, these
      properties can prevent metabolic labeling studies where subsequent tissue
      survival is needed. To bypass the metabolic pathways responsible for toxicity,
      while maintaining the ability to be metabolically incorporated into DNA, we
      synthesized and evaluated a small family of arabinofuranosyl-ethynyluracil
      derivatives. Among these, (2'S)-2'-deoxy-2'-fluoro-5-ethynyluridine (F-ara-EdU)
      exhibited selective DNA labeling, yet had a minimal impact on genome function in
      diverse tissue types. Metabolic incorporation of F-ara-EdU into DNA was readily
      detectable using copper(I)-catalyzed azide-alkyne "click" reactions with
      fluorescent azides. F-ara-EdU is less toxic than both BrdU and EdU, and it can be
      detected with greater sensitivity in experiments where long-term cell survival
      and/or deep-tissue imaging are desired. In contrast to previously reported 2'
      arabino modified nucleosides and EdU, F-ara-EdU causes little or no cellular
      arrest or DNA synthesis inhibition. F-ara-EdU is therefore ideally suited for
      pulse-chase experiments aimed at "birth dating" DNA in vivo. As a demonstration,
      Zebrafish embryos were microinjected with F-ara-EdU at the one-cell stage and
      chased by BrdU at 10 h after fertilization. Following 3 d of development, complex
      patterns of quiescent/senescent cells containing only F-ara-EdU were observed in
      larvae along the dorsal side of the notochord and epithelia. Arabinosyl
      nucleoside derivatives therefore provide unique and effective means to introduce
      bioorthogonal functional groups into DNA for diverse applications in basic
      research, biotechnology, and drug discovery.

PMID- 22143760
TI  - Economic and energetic analysis of capturing CO2 from ambient air.
AB  - Capturing carbon dioxide from the atmosphere ("air capture") in an industrial
      process has been proposed as an option for stabilizing global CO(2)
      concentrations. Published analyses suggest these air capture systems may cost a
      few hundred dollars per tonne of CO(2), making it cost competitive with
      mainstream CO(2) mitigation options like renewable energy, nuclear power, and
      carbon dioxide capture and storage from large CO(2) emitting point sources. We
      investigate the thermodynamic efficiencies of commercial separation systems as
      well as trace gas removal systems to better understand and constrain the energy
      requirements and costs of these air capture systems. Our empirical analyses of
      operating commercial processes suggest that the energetic and financial costs of
      capturing CO(2) from the air are likely to have been underestimated.
      Specifically, our analysis of existing gas separation systems suggests that,
      unless air capture significantly outperforms these systems, it is likely to
      require more than 400 kJ of work per mole of CO(2), requiring it to be powered by
      CO(2)-neutral power sources in order to be CO(2) negative. We estimate that total
      system costs of an air capture system will be on the order of $1,000 per tonne of
      CO(2), based on experience with as-built large-scale trace gas removal systems.

PMID- 22143761
TI  - Open conformation of human DOPA decarboxylase reveals the mechanism of PLP
      addition to Group II decarboxylases.
AB  - DOPA decarboxylase, the dimeric enzyme responsible for the synthesis of
      neurotransmitters dopamine and serotonin, is involved in severe neurological
      diseases such as Parkinson disease, schizophrenia, and depression. Binding of the
      pyridoxal-5'-phosphate (PLP) cofactor to the apoenzyme is thought to represent a
      central mechanism for the regulation of its activity. We solved the structure of
      the human apoenzyme and found it exists in an unexpected open conformation:
      compared to the pig kidney holoenzyme, the dimer subunits move 20 A apart and the
      two active sites become solvent exposed. Moreover, by tuning the PLP
      concentration in the crystals, we obtained two more structures with different
      conformations of the active site. Analysis of three-dimensional data coupled to a
      kinetic study allows to identify the structural determinants of the open/close
      conformational change occurring upon PLP binding and thereby propose a model for
      the preferential degradation of the apoenzymes of Group II decarboxylases.

PMID- 22143762
TI  - Computational design of a symmetric homodimer using beta-strand assembly.
AB  - Computational design of novel protein-protein interfaces is a test of our
      understanding of protein interactions and has the potential to allow modification
      of cellular physiology. Methods for designing high-affinity interactions that
      adopt a predetermined binding mode have proved elusive, suggesting the need for
      new strategies that simplify the design process. A solvent-exposed backbone on a
      beta-strand is thought of as "sticky" and beta-strand pairing stabilizes many
      naturally occurring protein complexes. Here, we computationally redesign a
      monomeric protein to form a symmetric homodimer by pairing exposed beta-strands
      to form an intermolecular beta-sheet. A crystal structure of the designed complex
      closely matches the computational model (rmsd = 1.0 A). This work demonstrates
      that beta-strand pairing can be used to computationally design new interactions
      with high accuracy.

PMID- 22143763
TI  - Multiple molecular architectures of the eye lens chaperone alphaB-crystallin
      elucidated by a triple hybrid approach.
AB  - The molecular chaperone alphaB-crystallin, the major player in maintaining the
      transparency of the eye lens, prevents stress-damaged and aging lens proteins
      from aggregation. In nonlenticular cells, it is involved in various neurological
      diseases, diabetes, and cancer. Given its structural plasticity and dynamics,
      structure analysis of alphaB-crystallin presented hitherto a formidable
      challenge. Here we present a pseudoatomic model of a 24-meric alphaB-crystallin
      assembly obtained by a triple hybrid approach combining data from cryoelectron
      microscopy, NMR spectroscopy, and structural modeling. The model, confirmed by
      cross-linking and mass spectrometry, shows that the subunits interact within the
      oligomer in different, defined conformations. We further present the molecular
      architectures of additional well-defined alphaB-crystallin assemblies with larger
      or smaller numbers of subunits, provide the mechanism how "heterogeneity" is
      achieved by a small set of defined structural variations, and analyze the factors
      modulating the oligomer equilibrium of alphaB-crystallin and thus its chaperone
      activity.

PMID- 22143765
TI  - Nonlinear detection of paleoclimate-variability transitions possibly related to
      human evolution.
AB  - Potential paleoclimatic driving mechanisms acting on human evolution present an
      open problem of cross-disciplinary scientific interest. The analysis of
      paleoclimate archives encoding the environmental variability in East Africa
      during the past 5 Ma has triggered an ongoing debate about possible candidate
      processes and evolutionary mechanisms. In this work, we apply a nonlinear
      statistical technique, recurrence network analysis, to three distinct marine
      records of terrigenous dust flux. Our method enables us to identify three epochs
      with transitions between qualitatively different types of environmental
      variability in North and East Africa during the (i) Middle Pliocene (3.35-3.15 Ma
      B.P.), (ii) Early Pleistocene (2.25-1.6 Ma B.P.), and (iii) Middle Pleistocene
      (1.1-0.7 Ma B.P.). A deeper examination of these transition periods reveals
      potential climatic drivers, including (i) large-scale changes in ocean currents
      due to a spatial shift of the Indonesian throughflow in combination with an
      intensification of Northern Hemisphere glaciation, (ii) a global reorganization
      of the atmospheric Walker circulation induced in the tropical Pacific and Indian
      Ocean, and (iii) shifts in the dominating temporal variability pattern of glacial
      activity during the Middle Pleistocene, respectively. A reexamination of the
      available fossil record demonstrates statistically significant coincidences
      between the detected transition periods and major steps in hominin evolution.
      This result suggests that the observed shifts between more regular and more
      erratic environmental variability may have acted as a trigger for rapid change in
      the development of humankind in Africa.

PMID- 22143764
TI  - The genomic binding sites of a noncoding RNA.
AB  - Long noncoding RNAs (lncRNAs) have important regulatory roles and can function at
      the level of chromatin. To determine where lncRNAs bind to chromatin, we
      developed capture hybridization analysis of RNA targets (CHART), a hybridization
      based technique that specifically enriches endogenous RNAs along with their
      targets from reversibly cross-linked chromatin extracts. CHART was used to enrich
      the DNA and protein targets of endogenous lncRNAs from flies and humans. This
      analysis was extended to genome-wide mapping of roX2, a well-studied ncRNA
      involved in dosage compensation in Drosophila. CHART revealed that roX2 binds at
      specific genomic sites that coincide with the binding sites of proteins from the
      male-specific lethal complex that affects dosage compensation. These results
      reveal the genomic targets of roX2 and demonstrate how CHART can be used to study
      RNAs in a manner analogous to chromatin immunoprecipitation for proteins.

PMID- 22143766
TI  - Targeted knock-down of a structurally atypical zebrafish 12S-lipoxygenase leads
      to severe impairment of embryonic development.
AB  - Lipoxygenases (LO) are a class of dioxygenases, which form hydroperoxy, hydroxy,
      and epoxy derivatives of arachidonic acid with distinct positional and
      stereochemical configurations. In man, there are two known types of 12-LO that
      are distinguished by their expression patterns and catalytic properties. The
      platelet 12S-LO plays a role in platelet aggregation and 12R-LO seems to be
      important for normal skin function. Using BLAST searches of the zebrafish (zf)
      genome we identified one candidate zf12-LO gene with 43% identity with human 12R
      LO at the mRNA level and the deduced primary sequence carried the so called
      "Coffa" structural determinant (Gly residue) for R stereoselectivity of LOs.
      However, incubations of recombinant, purified, zf12-LO with arachidonic acid
      revealed exclusive formation of 12(S)-hydroperoxy-eicosatetraenoic acid. Further
      studies with immunohistochemistry showed prominent expression of zf12-LO in the
      cell nuclei of skin epithelium, the epithelial lining of the stomodeum, and the
      pharyngeal pouches in zf embryos. To probe its function, zf12-LO was subjected to
      targeted knock-down in zf embryos, resulting in the development of a severe
      phenotype, characterized by abnormal development of the brain, the eyes, and the
      tail as well as pericardial and yolk sac edema. Hence, we have identified a
      unique vertebrate 12S-LO that breaks the current structure-function paradigms for
      S and R stereo-specificity and with critical roles in normal embryonic
      development.

PMID- 22143767
TI  - Sterol-induced degradation of HMG CoA reductase depends on interplay of two
      Insigs and two ubiquitin ligases, gp78 and Trc8.
AB  - Accumulation of sterols in membranes of the endoplasmic reticulum (ER) leads to
      the accelerated ubiquitination and proteasomal degradation of 3-hydroxy-3
      methylglutaryl coenzyme A reductase, a rate-limiting enzyme in synthesis of
      cholesterol and nonsterol isoprenoids. This degradation results from sterol
      induced binding of reductase to the Insig-1 or Insig-2 proteins of ER membranes.
      We previously reported that in immortalized human fibroblasts (SV-589 cells)
      Insig-1, but not Insig-2, recruits gp78, a membrane-bound RING-finger ubiquitin
      ligase. We now report that both Insig-1 and Insig-2 bind another membrane-bound
      RING-finger ubiquitin ligase called Trc8. Knockdown of either gp78 or Trc8 in SV
      589 cells through RNA interference (RNAi) inhibited sterol-induced ubiquitination
      of reductase and inhibited sterol-induced degradation by 50-60%. The combined
      knockdown of gp78 and Trc8 produced a more complete inhibition of degradation (>
      90%). Knockdown of gp78 led to a three to fourfold increase in levels of Trc8 and
      Insig-1 proteins, which opposed the inhibitory action of gp78. In contrast,
      knockdown of Trc8 had no effect on gp78 or Insig-1. The current results suggest
      that sterol-induced ubiquitination and proteasomal degradation of reductase is
      dictated by the complex interplay of at least four proteins: Insig-1, Insig-2,
      gp78, and Trc8. Variations in the concentrations of any one of these proteins may
      account for differences in cell- and/or tissue-specific regulation of reductase
      degradation.

PMID- 22143768
TI  - An enumerative stepwise ansatz enables atomic-accuracy RNA loop modeling.
AB  - Atomic-accuracy structure prediction of macromolecules should be achievable by
      optimizing a physically realistic energy function but is presently precluded by
      incomplete sampling of a biopolymer's many degrees of freedom. We present herein
      a working hypothesis, called the "stepwise ansatz," for recursively constructing
      well-packed atomic-detail models in small steps, enumerating several million
      conformations for each monomer, and covering all build-up paths. By making use of
      high-performance computing and the Rosetta framework, we provide first tests of
      this hypothesis on a benchmark of 15 RNA loop-modeling problems drawn from
      riboswitches, ribozymes, and the ribosome, including 10 cases that are not
      solvable by current knowledge-based modeling approaches. For each loop problem,
      this deterministic stepwise assembly method either reaches atomic accuracy or
      exposes flaws in Rosetta's all-atom energy function, indicating the resolution of
      the conformational sampling bottleneck. As a further rigorous test, we have
      carried out a blind all-atom prediction for a noncanonical RNA motif, the C7.2
      tetraloop/receptor, and validated this model through nucleotide-resolution
      chemical mapping experiments. Stepwise assembly is an enumerative, ab initio
      build-up method that systematically outperforms existing Monte Carlo and
      knowledge-based methods for 3D structure prediction.

PMID- 22143769
TI  - Electrostatic origin of the mechanochemical rotary mechanism and the catalytic
      dwell of F1-ATPase.
AB  - Understanding the nature of energy transduction in life processes requires a
      quantitative description of the energetics of the conversion of ATP to ADP by
      ATPases. Previous attempts to do so have provided an interesting insight but
      could not account for the rotary mechanism by a nonphenomenological
      structure/energy description. In particular it has been very challenging to
      account for the observations of the 80 degrees  and 40 degrees  rotational
      substates, without any prior information about such states in the simulation
      procedure. Here we use a coarse-grained model of F1-ATPase and generate, without
      the adjustment of phenomenological parameters, a structure-based free energy
      landscape that reproduces the energetics of the mechanochemical process. It is
      found that the landscape along the relevant rotary path is determined by the
      electrostatic free energy and not by steric effects. Furthermore, the generated
      surface and the corresponding Langevin dynamics simulations identify a hidden
      conformational barrier that provides a new fundamental interpretation of the
      catalytic dwell and illuminate the nature of the energy conversion process.

PMID- 22143770
TI  - Structural insights into protein arginine symmetric dimethylation by PRMT5.
AB  - Symmetric and asymmetric dimethylation of arginine are isomeric protein
      posttranslational modifications with distinct biological effects, evidenced by
      the methylation of arginine 3 of histone H4 (H4R3): symmetric dimethylation of
      H4R3 leads to repression of gene expression, while asymmetric dimethylation of
      H4R3 is associated with gene activation. The enzymes catalyzing these
      modifications share identifiable sequence similarities, but the relationship
      between their catalytic mechanisms is unknown. Here we analyzed the structure of
      a prototypic symmetric arginine dimethylase, PRMT5, and discovered that a
      conserved phenylalanine in the active site is critical for specifying symmetric
      addition of methyl groups. Changing it to a methionine significantly elevates the
      overall methylase activity, but also converts PRMT5 to an enzyme that catalyzes
      both symmetric and asymmetric dimethylation of arginine. Our results demonstrate
      a common catalytic mechanism intrinsic to both symmetric and asymmetric arginine
      dimethylases, and show that steric constrains in the active sites play an
      essential role in determining the product specificity of arginine methylases.
      This discovery also implies a potentially regulatable outcome of arginine
      dimethylation that may provide versatile control of eukaryotic gene expression.

PMID- 22143771
TI  - Energy landscape of the reactions governing the Na+ deeply occluded state of the
      Na+/K+-ATPase in the giant axon of the Humboldt squid.
AB  - The Na(+)/K(+) pump is a nearly ubiquitous membrane protein in animal cells that
      uses the free energy of ATP hydrolysis to alternatively export 3Na(+) from the
      cell and import 2K(+) per cycle. This exchange of ions produces a steady-state
      outwardly directed current, which is proportional in magnitude to the turnover
      rate. Under certain ionic conditions, a sudden voltage jump generates temporally
      distinct transient currents mediated by the Na(+)/K(+) pump that represent the
      kinetics of extracellular Na(+) binding/release and Na(+) occlusion/deocclusion
      transitions. For many years, these events have escaped a proper thermodynamic
      treatment due to the relatively small electrical signal. Here, taking the
      advantages offered by the large diameter of the axons from the squid Dosidicus
      gigas, we have been able to separate the kinetic components of the transient
      currents in an extended temperature range and thus characterize the energetic
      landscape of the pump cycle and those transitions associated with the
      extracellular release of the first Na(+) from the deeply occluded state.
      Occlusion/deocclusion transition involves large changes in enthalpy and entropy
      as the ion is exposed to the external milieu for release. Binding/unbinding is
      substantially less costly, yet larger than predicted for the energetic cost of an
      ion diffusing through a permeation pathway, which suggests that ion
      binding/unbinding must involve amino acid side-chain rearrangements at the site.

PMID- 22143772
TI  - Adding a dimension to the infrared spectra of interfaces using heterodyne
      detected 2D sum-frequency generation (HD 2D SFG) spectroscopy.
AB  - In the last ten years, two-dimensional infrared spectroscopy has become an
      important technique for studying molecular structures and dynamics. We report the
      implementation of heterodyne detected two-dimensional sum-frequency generation
      (HD 2D SFG) spectroscopy, which is the analog of 2D infrared (2D IR)
      spectroscopy, but is selective to noncentrosymmetric systems such as interfaces.
      We implement the technique using mid-IR pulse shaping, which enables rapid
      scanning, phase cycling, and automatic phasing. Absorptive spectra are obtained,
      that have the highest frequency resolution possible, from which we extract the
      rephasing and nonrephasing signals that are sometimes preferred. Using this
      technique, we measure the vibrational mode of CO adsorbed on a polycrystalline Pt
      surface. The 2D spectrum reveals a significant inhomogenous contribution to the
      spectral line shape, which is quantified by simulations. This observation
      indicates that the surface conformation and environment of CO molecules is more
      complicated than the simple "atop" configuration assumed in previous work. Our
      method can be straightforwardly incorporated into many existing SFG
      spectrometers. The technique enables one to quantify inhomogeneity, vibrational
      couplings, spectral diffusion, chemical exchange, and many other properties
      analogous to 2D IR spectroscopy, but specifically for interfaces.

PMID- 22143773
TI  - Regulation of phenotypic heterogeneity permits Salmonella evasion of the host
      caspase-1 inflammatory response.
AB  - Sensing and adapting to the environment is one strategy by which bacteria attempt
      to maximize fitness in an unpredictable world; another is the stochastic
      generation of phenotypically distinct subgroups within a genetically clonal
      population. In culture, Salmonella Typhimurium populations are bistable for the
      expression of flagellin. We report that YdiV controls this expression pattern by
      preventing transcription of the sigma factor that recruits RNA polymerase to the
      flagellin promoter. Bistability ensues when the sigma factor is repressed in a
      subpopulation of cells, resulting in two phenotypes: flagellin expressors and
      flagellin nonexpressors. Although the ability to swim is presumably a critical
      survival trait, flagellin activates eukaryotic defense pathways, and Salmonella
      restrict the production of flagellin during systemic infection. Salmonella
      mutants lacking YdiV are unable to fully repress flagellin at systemic sites,
      rendering them vulnerable to caspase-1 mediated colonization restriction. Thus, a
      regulatory mechanism producing bistability also impacts Salmonella virulence.

PMID- 22143774
TI  - Ouabain modulates ciliogenesis in epithelial cells.
AB  - The exchange of substances between higher organisms and the environment occurs
      across transporting epithelia whose basic features are tight junctions (TJs) that
      seal the intercellular space, and polarity, which enables cells to transport
      substances vectorially. In a previous study, we demonstrated that 10 nM ouabain
      modulates TJs, and we now show that it controls polarity as well. We gauge
      polarity through the development of a cilium at the apical domain of Madin-Darby
      canine kidney cells (MDCK, epithelial dog kidney). Ouabain accelerates
      ciliogenesis in an ERK1/2-dependent manner. Claudin-2, a molecule responsible for
      the Na(+) and H(2)O permeability of the TJs, is also present at the cilium, as it
      colocalizes and coprecipitates with acetylated alpha-tubulin. Ouabain modulates
      claudin-2 localization at the cilium through ERK1/2. Comparing wild-type and
      ouabain-resistant MDCK cells, we show that ouabain acts through Na(+),K(+)
      ATPase. Taken together, our previous and present results support the possibility
      that ouabain constitutes a hormone that modulates the transporting epithelial
      phenotype, thereby playing a crucial role in metazoan life.

PMID- 22143775
TI  - Multimodal image coregistration and inducible selective cell ablation to evaluate
      imaging ligands.
AB  - We combined multimodal imaging (bioluminescence, X-ray computed tomography, and
      PET), tomographic reconstruction of bioluminescent sources, and two unique,
      complementary models to evaluate three previously synthesized PET radiotracers
      thought to target pancreatic beta cells. The three radiotracers
      {[(18)F]fluoropropyl-(+)-dihydrotetrabenazine ([(18)F]FP-DTBZ), [(18)F](+)-2
      oxiranyl-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-2,3,4,6,7,11b-hexahydro-1H
      pyrido[2,1-a]isoquinoline ((18)F-AV-266), and (2S,3R,11bR)-9-(3-fluoropropoxy)-2
      (hydroxymethyl)-3-isobutyl-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1
      a]isoquinolin-2-ol ((18)F-AV-300)} bind vesicular monoamine transporter 2.
      Tomographic reconstruction of the bioluminescent signal in mice expressing
      luciferase only in pancreatic beta cells was used to delineate the pancreas and
      was coregistered with PET and X-ray computed tomography images. This strategy
      enabled unambiguous identification of the pancreas on PET images, permitting
      accurate quantification of the pancreatic PET signal. We show here that, after
      conditional, specific, and rapid mouse beta-cell ablation, beta-cell loss was
      detected by bioluminescence imaging but not by PET imaging, given that the
      pancreatic signal provided by three PET radiotracers was not altered. To
      determine whether these ligands bound human beta cells in vivo, we imaged mice
      transplanted with luciferase-expressing human islets. The human islets were
      imaged by bioluminescence but not with the PET ligands, indicating that these
      vesicular monoamine transporter 2-directed ligands did not specifically bind beta
      cells. These data demonstrate the utility of coregistered multimodal imaging as a
      platform for evaluation and validation of candidate ligands for imaging islets.

PMID- 22143776
TI  - Phytophthora infestans effector AVRblb2 prevents secretion of a plant immune
      protease at the haustorial interface.
AB  - In response to pathogen attack, plant cells secrete antimicrobial molecules at
      the site of infection. However, how plant pathogens interfere with defense
      related focal secretion remains poorly known. Here we show that the host
      translocated RXLR-type effector protein AVRblb2 of the Irish potato famine
      pathogen Phytophthora infestans focally accumulates around haustoria, specialized
      infection structures that form inside plant cells, and promotes virulence by
      interfering with the execution of host defenses. AVRblb2 significantly enhances
      susceptibility of host plants to P. infestans by targeting the host papain-like
      cysteine protease C14 and specifically preventing its secretion into the
      apoplast. Plants altered in C14 expression were significantly affected in
      susceptibility to P. infestans in a manner consistent with a positive role of C14
      in plant immunity. Our findings point to a unique counterdefense strategy that
      plant pathogens use to neutralize secreted host defense proteases. Effectors,
      such as AVRblb2, can be used as molecular probes to dissect focal immune
      responses at pathogen penetration sites.

PMID- 22143777
TI  - Plastid terminal oxidase 2 (PTOX2) is the major oxidase involved in
      chlororespiration in Chlamydomonas.
AB  - By homology with the unique plastid terminal oxidase (PTOX) found in plants, two
      genes encoding oxidases have been found in the Chlamydomonas genome, PTOX1 and
      PTOX2. Here we report the identification of a knockout mutant of PTOX2. Its
      molecular and functional characterization demonstrates that it encodes the
      oxidase most predominantly involved in chlororespiration in this algal species.
      In this mutant, the plastoquinone pool is constitutively reduced under dark
      aerobic conditions, resulting in the mobile light-harvesting complexes being
      mainly, but reversibly, associated with photosystem I. Accordingly, the ptox2
      mutant shows lower fitness than wild type when grown under phototrophic
      conditions. Single and double mutants devoid of the cytochrome b(6)f complex and
      PTOX2 were used to measure the oxidation rates of plastoquinols via PTOX1 and
      PTOX2. Those lacking both the cytochrome b(6)f complex and PTOX2 were more
      sensitive to light than the single mutants lacking either the cytochrome b(6)f
      complex or PTOX2, which discloses the role of PTOX2 under extreme conditions
      where the plastoquinone pool is overreduced. A model for chlororespiration is
      proposed to relate the electron flow rate through these alternative pathways and
      the redox state of plastoquinones in the dark. This model suggests that, in green
      algae and plants, the redox poise results from the balanced accumulation of PTOX
      and NADPH dehydrogenase.

PMID- 22143778
TI  - Rice consumption contributes to arsenic exposure in US women.
AB  - Emerging data indicate that rice consumption may lead to potentially harmful
      arsenic exposure. However, few human data are available, and virtually none exist
      for vulnerable periods such as pregnancy. Here we document a positive association
      between rice consumption and urinary arsenic excretion, a biomarker of recent
      arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a
      urine sample and 3-d dietary record for water, fish/seafood, and rice. We also
      tested women's home tap water for arsenic, which we combined with tap water
      consumption to estimate arsenic exposure through water. Women who reported rice
      intake (n = 73) consumed a median of 28.3 g/d, which is ~0.5 cup of cooked rice
      each day. In general linear models adjusted for age and urinary dilution, both
      rice consumption (g, dry mass/d) and arsenic exposure through water (MUg/d) were
      significantly associated with natural log-transformed total urinary arsenic
      (betarice = 0.009, betawater = 0.028, both P < 0.0001), as well as inorganic
      arsenic, monomethylarsonic acid, and dimethylarsinic acid (each P < 0.005). Based
      on total arsenic, consumption of 0.56 cup/d of cooked rice was comparable to
      drinking 1 L/d of 10 MUg As/L water, the current US maximum contaminant limit. US
      rice consumption varies, averaging ~0.5 cup/d, with Asian Americans consuming an
      average of >2 cups/d. Rice arsenic content and speciation also vary, with some
      strains predominated by dimethylarsinic acid, particularly those grown in the
      United States. Our findings along with others indicate that rice consumption
      should be considered when designing arsenic reduction strategies in the United
      States.

PMID- 22143779
TI  - A nonreplicating subunit vaccine protects mice against lethal Ebola virus
      challenge.
AB  - Ebola hemorrhagic fever is an acute and often deadly disease caused by Ebola
      virus (EBOV). The possible intentional use of this virus against human
      populations has led to design of vaccines that could be incorporated into a
      national stockpile for biological threat reduction. We have evaluated the
      immunogenicity and efficacy of an EBOV vaccine candidate in which the viral
      surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that
      recognizes an epitope in glycoprotein, resulting in the production of Ebola
      immune complexes (EICs). Although antigen-antibody immune complexes are known to
      be efficiently processed and presented to immune effector cells, we found that
      codelivery of the EIC with Toll-like receptor agonists elicited a more robust
      antibody response in mice than did EIC alone. Among the compounds tested,
      polyinosinic:polycytidylic acid (PIC, a Toll-like receptor 3 agonist) was highly
      effective as an adjuvant agent. After vaccinating mice with EIC plus PIC, 80% of
      the animals were protected against a lethal challenge with live EBOV (30,000
      LD(50) of mouse adapted virus). Surviving animals showed a mixed Th1/Th2 response
      to the antigen, suggesting this may be important for protection. Survival after
      vaccination with EIC plus PIC was statistically equivalent to that achieved with
      an alternative viral vector vaccine candidate reported in the literature. Because
      nonreplicating subunit vaccines offer the possibility of formulation for cost
      effective, long-term storage in biothreat reduction repositories, EIC is an
      attractive option for public health defense measures.

PMID- 22143780
TI  - Heterozygote advantage as a natural consequence of adaptation in diploids.
AB  - Molecular adaptation is typically assumed to proceed by sequential fixation of
      beneficial mutations. In diploids, this picture presupposes that for most
      adaptive mutations, the homozygotes have a higher fitness than the heterozygotes.
      Here, we show that contrary to this expectation, a substantial proportion of
      adaptive mutations should display heterozygote advantage. This feature of
      adaptation in diploids emerges naturally from the primary importance of the
      fitness of heterozygotes for the invasion of new adaptive mutations. We formalize
      this result in the framework of Fisher's influential geometric model of
      adaptation. We find that in diploids, adaptation should often proceed through a
      succession of short-lived balanced states that maintain substantially higher
      levels of phenotypic and fitness variation in the population compared with
      classic adaptive walks. In fast-changing environments, this variation produces a
      diversity advantage that allows diploids to remain better adapted compared with
      haploids despite the disadvantage associated with the presence of unfit
      homozygotes. The short-lived balanced states arising during adaptive walks should
      be mostly invisible to current scans for long-term balancing selection. Instead,
      they should leave signatures of incomplete selective sweeps, which do appear to
      be common in many species. Our results also raise the possibility that balancing
      selection, as a natural consequence of frequent adaptation, might play a more
      prominent role among the forces maintaining genetic variation than is commonly
      recognized.

PMID- 22143781
TI  - Dynamic model of flexible phytoplankton nutrient uptake.
AB  - The metabolic machinery of marine microbes can be remarkably plastic, allowing
      organisms to persist under extreme nutrient limitation. With some exceptions,
      most theoretical approaches to nutrient uptake in phytoplankton are largely
      dominated by the classic Michaelis-Menten (MM) uptake functional form, whose
      constant parameters cannot account for the observed plasticity in the uptake
      apparatus. Following seminal ideas by earlier researchers, we propose a simple
      cell-level model based on a dynamic view of the uptake process whereby the cell
      can regulate the synthesis of uptake proteins in response to changes in both
      internal and external nutrient concentrations. In our flexible approach, the
      maximum uptake rate and nutrient affinity increase monotonically as the external
      nutrient concentration decreases. For low to medium nutrient availability, our
      model predicts uptake and growth rates larger than the classic MM counterparts,
      while matching the classic MM results for large nutrient concentrations. These
      results have important consequences for global coupled models of ocean
      circulation and biogeochemistry, which lack this regulatory mechanism and are
      thus likely to underestimate phytoplankton abundances and growth rates in
      oligotrophic regions of the ocean.

PMID- 22143782
TI  - Thomas Eisner: Interpreter extraordinaire of nature's chemistry.

PMID- 22143783
TI  - Antigen-specific induced Foxp3+ regulatory T cells are generated following
      CD40/CD154 blockade.
AB  - Blockade of the CD40/CD154 pathway potently attenuates T-cell responses in models
      of autoimmunity, inflammation, and transplantation. Indeed, CD40 pathway blockade
      remains one of the most powerful methods of prolonging graft survival in models
      of transplantation. But despite this effectiveness, the cellular and molecular
      mechanisms underlying the protective effects of CD40 pathway blockade are
      incompletely understood. Furthermore, the relative contributions of deletion,
      anergy, and regulation have not been measured in a model in which donor-reactive
      CD4(+) and CD8(+) T-cell responses can be assessed simultaneously. To investigate
      the impact of CD40/CD154 pathway blockade on graft-specific T-cell responses, a
      transgenic mouse model was used in which recipients containing ovalbumin-specific
      CD4(+) and CD8(+) TCR transgenic T cells were grafted with skin expressing
      ovalbumin in the presence or absence of anti-CD154 and donor-specific
      transfusion. The results indicated that CD154 blockade altered the kinetics of
      donor-reactive CD8(+) T-cell expansion, delaying differentiation into IFN
      gamma(+) TNF(+) multifunctional cytokine producers. The eventual differentiation
      of cytokine-producing effectors in tolerant animals coincided with the emergence
      of an antigen-specific CD4(+) CD25(hi) Foxp3(+) T-cell population, which did not
      arise from endogenous natural T(reg) but rather were peripherally generated from
      naive Foxp3(-) precursors.

PMID- 22143784
TI  - Native Americans experienced a strong population bottleneck coincident with
      European contact.
AB  - The genetic and demographic impact of European contact with Native Americans has
      remained unclear despite recent interest. Whereas archeological and historical
      records indicate that European contact resulted in widespread mortality from
      various sources, genetic studies have found little evidence of a recent
      contraction in Native American population size. In this study we use a large
      dataset including both ancient and contemporary mitochondrial DNA to construct a
      high-resolution portrait of the Holocene and late Pleistocene population size of
      indigenous Americans. Our reconstruction suggests that Native Americans suffered
      a significant, although transient, contraction in population size some 500 y
      before the present, during which female effective size was reduced by ~50%. These
      results support analyses of historical records indicating that European
      colonization induced widespread mortality among indigenous Americans.

PMID- 22143785
TI  - Global population trajectories of tunas and their relatives.
AB  - Tunas and their relatives dominate the world's largest ecosystems and sustain
      some of the most valuable fisheries. The impacts of fishing on these species have
      been debated intensively over the past decade, giving rise to divergent views on
      the scale and extent of the impacts of fisheries on pelagic ecosystems. We use
      all available age-structured stock assessments to evaluate the adult biomass
      trajectories and exploitation status of 26 populations of tunas and their
      relatives (17 tunas, 5 mackerels, and 4 Spanish mackerels) from 1954 to 2006.
      Overall, populations have declined, on average, by 60% over the past half
      century, but the decline in the total adult biomass is lower (52%), driven by a
      few abundant populations. The trajectories of individual populations depend on
      the interaction between life histories, ecology, and fishing pressure. The
      steepest declines are exhibited by two distinct groups: the largest, longest
      lived, highest value temperate tunas and the smaller, short-lived mackerels, both
      with most of their populations being overexploited. The remaining populations,
      mostly tropical tunas, have been fished down to approximately maximum sustainable
      yield levels, preventing further expansion of catches in these fisheries. Fishing
      mortality has increased steadily to the point where around 12.5% of the tunas and
      their relatives are caught each year globally. Overcapacity of these fisheries is
      jeopardizing their long-term sustainability. To guarantee higher catches,
      stabilize profits, and reduce collateral impacts on marine ecosystems requires
      the rebuilding of overexploited populations and stricter management measures to
      reduce overcapacity and regulate threatening trade.

PMID- 22143786
TI  - Sterile inflammation of endothelial cell-derived apoptotic bodies is mediated by
      interleukin-1alpha.
AB  - Sterile inflammation resulting from cell death is due to the release of cell
      contents normally inactive and sequestered within the cell; fragments of cell
      membranes from dying cells also contribute to sterile inflammation. Endothelial
      cells undergoing stress-induced apoptosis release membrane microparticles, which
      become vehicles for proinflammatory signals. Here, we show that stress-activated
      endothelial cells release two distinct populations of particles: One population
      consists of membrane microparticles (<1 MUm, annexin V positive without DNA and
      no histones) and another larger (1-3 MUm) apoptotic body-like particles
      containing nuclear fragments and histones, representing apoptotic bodies.
      Contrary to present concepts, endothelial microparticles do not contain IL-1alpha
      and do not induce neutrophilic chemokines in vitro. In contrast, the large
      apoptotic bodies contain the full-length IL-1alpha precursor and the processed
      mature form. In vitro, these apoptotic bodies induce monocyte chemotactic protein
      1 and IL-8 chemokine secretion in an IL-1alpha-dependent but IL-1beta-independent
      fashion. Injection of these apoptotic bodies into the peritoneal cavity of mice
      induces elevated serum neutrophil-inducing chemokines, which was prevented by
      cotreatment with the IL-1 receptor antagonist. Consistently, injection of these
      large apoptotic bodies into the peritoneal cavity induced a neutrophilic
      infiltration that was prevented by IL-1 blockade. Although apoptosis is
      ordinarily considered noninflammatory, these data demonstrate that
      nonphagocytosed endothelial apoptotic bodies are inflammatory, providing a
      vehicle for IL-1alpha and, therefore, constitute a unique mechanism for sterile
      inflammation.

PMID- 22143787
TI  - Characteristics of Borrelia hermsii infection in human hematopoietic stem cell
      engrafted mice mirror those of human relapsing fever.
AB  - Rodents are natural reservoirs for a variety of species of Borrelia that cause
      relapsing fever (RF) in humans. The murine model of this disease recapitulates
      many of the clinical manifestations of the human disease and has revealed that T
      cell-independent antibody responses are required to resolve the bacteremic
      episodes. However, it is not clear whether such protective humoral responses are
      mounted in humans. We examined Borrelia hermsii infection in human hematopoietic
      stem cell-engrafted nonobese diabetic/SCID/IL-2Rgamma(null) mice: "human immune
      system mice" (HISmice). Infection of these mice, which are severely deficient in
      lymphoid and myeloid compartments, with B. hermsii resulted in persistent
      bacteremia. In contrast, this infection in HISmice resulted in recurrent episodes
      of bacteremia, the hallmark of RF. The resolution of the primary episode of
      bacteremia was concurrent with the generation of B. hermsii-specific human IgM.
      Remarkably, HISmice generated antibody responses to the B. hermsii outer-membrane
      protein Factor H binding protein A. Sera from humans infected by B. hermsii have
      a similar reactivity, and studies in mice have shown that this response is
      generated by the B1b cell subset. HISmice contain several B-cell subsets,
      including those with the phenotype CD20(+)CD27(+)CD43(+)CD70(-), a proposed human
      equivalent of mouse B1 cells. Reduction of B cells by administration of anti
      human CD20 antibody resulted in diminished anti-B. hermsii responses and
      persistent bacteremia in HISmice. These data indicate that analysis of B. hermsii
      infection in HISmice will serve as a model in which to study the cellular and
      molecular mechanisms involved in controlling human RF.

PMID- 22143788
TI  - Intercontinental differences in resource use reveal the importance of mutualisms
      in fire ant invasions.
AB  - Mutualisms play key roles in the functioning of ecosystems. However, reciprocally
      beneficial interactions that involve introduced species also can enhance invasion
      success and in doing so compromise ecosystem integrity. For example, the growth
      and competitive ability of introduced plant species can increase when fungal or
      microbial associates provide limiting nutrients. Mutualisms also may aid animal
      invasions, but how such systems may promote invasion success has received
      relatively little attention. Here we examine how access to food-for-protection
      mutualisms involving the red imported fire ant (Solenopsis invicta) aids the
      success of this prominent invader. Intense interspecific competition in its
      native Argentina constrained the ability of S. invicta to benefit from honeydew
      producing Hemiptera (and other accessible sources of carbohydrates), whereas S.
      invicta dominated these resources in its introduced range in the United States.
      Consistent with this strong pattern, nitrogen isotopic data revealed that fire
      ants from populations in the United States occupy a lower trophic position than
      fire ants from Argentina. Laboratory and field experiments demonstrated that
      honeydew elevated colony growth, a crucial determinant of competitive
      performance, even when insect prey were not limiting. Carbohydrates, obtained
      largely through mutualistic partnerships with other organisms, thus represent
      critical resources that may aid the success of this widespread invasive species.
      These results illustrate the potential for mutualistic interactions to play a
      fundamental role in the establishment and spread of animal invasions.

PMID- 22143789
TI  - Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola
      virus immunoprotectant.
AB  - No countermeasures currently exist for the prevention or treatment of the severe
      sequelae of Filovirus (such as Ebola virus; EBOV) infection. To overcome this
      limitation in our biodefense preparedness, we have designed monoclonal antibodies
      (mAbs) which could be used in humans as immunoprotectants for EBOV, starting with
      a murine mAb (13F6) that recognizes the heavily glycosylated mucin-like domain of
      the virion-attached glycoprotein (GP). Point mutations were introduced into the
      variable region of the murine mAb to remove predicted human T-cell epitopes, and
      the variable regions joined to human constant regions to generate a mAb (h-13F6)
      appropriate for development for human use. We have evaluated the efficacy of
      three variants of h-13F6 carrying different glycosylation patterns in a lethal
      mouse EBOV challenge model. The pattern of glycosylation of the various mAbs was
      found to correlate to level of protection, with aglycosylated h-13F6 providing
      the least potent efficacy (ED(50) = 33 MUg). A version with typical heterogenous
      mammalian glycoforms (ED(50) = 11 MUg) had similar potency to the original murine
      mAb. However, h-13F6 carrying complex N-glycosylation lacking core fucose
      exhibited superior potency (ED(50) = 3 MUg). Binding studies using Fcgamma
      receptors revealed enhanced binding of nonfucosylated h-13F6 to mouse and human
      FcgammaRIII. Together the results indicate the presence of Fc N-glycans enhances
      the protective efficacy of h-13F6, and that mAbs manufactured with uniform
      glycosylation and a higher potency glycoform offer promise as biodefense
      therapeutics.

PMID- 22143790
TI  - Mouse digit tip regeneration is mediated by fate-restricted progenitor cells.
AB  - Regeneration of appendages is frequent among invertebrates as well as some
      vertebrates. However, in mammals this has been largely relegated to digit tip
      regeneration, as found in mice and humans. The regenerated structures are formed
      from a mound of undifferentiated cells called a blastema, found just below the
      site of amputation. The blastema ultimately gives rise to all of the tissues in
      the regenerate, excluding the epidermis, and has classically been thought of as a
      homogenous pool of pluripotent stem cells derived by dedifferentiation of stump
      tissue, although this has never been directly tested in the context of mammalian
      digit tip regeneration. Successful digit tip regeneration requires that the level
      of amputation be within the nail bed and depends on expression of Msx1. Because
      Msx1 is strongly expressed in the nail bed mesenchyme, it has been proposed that
      the Msx1-expressing cells represent a pluripotent cell population for the
      regenerating digit. In this report, we show that Msx1 is dynamically expressed
      during digit tip regeneration, and it does not mark a pluripotent stem cell
      population. Moreover, we show that both the ectoderm and mesoderm contain fate
      restricted progenitor populations that work in concert to regenerate their own
      lineages within the digit tip, supporting the hypothesis that the blastema is a
      heterogeneous pool of progenitor cells.

PMID- 22143791
TI  - Visuoauditory mappings between high luminance and high pitch are shared by
      chimpanzees (Pan troglodytes) and humans.
AB  - Humans share implicit preferences for certain cross-sensory combinations; for
      example, they consistently associate higher-pitched sounds with lighter colors,
      smaller size, and spikier shapes. In the condition of synesthesia, people may
      experience such cross-modal correspondences to a perceptual degree (e.g.,
      literally seeing sounds). So far, no study has addressed the question whether
      nonhuman animals share cross-modal correspondences as well. To establish the
      evolutionary origins of cross-modal mappings, we tested whether chimpanzees (Pan
      troglodytes) also associate higher pitch with higher luminance. Thirty-three
      humans and six chimpanzees were required to classify black and white squares
      according to their color while hearing irrelevant background sounds that were
      either high-pitched or low-pitched. Both species performed better when the
      background sound was congruent (high-pitched for white, low-pitched for black)
      than when it was incongruent (low-pitched for white, high-pitched for black). An
      inherent tendency to pair high pitch with high luminance hence evolved before the
      human lineage split from that of chimpanzees. Rather than being a culturally
      learned or a linguistic phenomenon, this mapping constitutes a basic feature of
      the primate sensory system.

PMID- 22143792
TI  - Notch1 regulates the expression of the multidrug resistance gene ABCC1/MRP1 in
      cultured cancer cells.
AB  - Multidrug resistance (MDR) is a barrier to successful cancer chemotherapy.
      Although MDR is associated with overexpression of ATP-binding cassette (ABC)
      membrane transporters, mechanisms behind their up-regulation are not entirely
      understood. The cleaved form of the Notch1 protein, intracellular Notch1
      (N1(IC)), is involved in transcriptional regulation of genes. To test whether
      Notch1 is involved in the expression of multidrug resistance-associated protein 1
      (ABCC1/MRP1; herein referred to as ABCC1), we measured N1(IC) and presenilin 1
      (PSEN1), the catalytic subunit of gamma-secretase required for Notch activation.
      We observed higher levels of N1(IC) and PSEN1 proteins as well as higher activity
      of N1(IC) in ABCC1-expressing MDR MCF7/VP cells compared with parental MCF7/WT
      cells. Reducing N1(IC) levels in MCF7/VP cells with either a gamma-secretase
      inhibitor or shRNA led to reduction of ABCC1. By contrast, ectopic expression of
      N1(IC) in MCF7/WT cells led to increased expression of ABCC1 and associated drug
      resistance, consistent with expression of this transporter. Inhibition of ABCC1
      reversed drug resistance of N1(IC)-overexpressing stable cells. Using an ABCC1
      promoter construct, we observed both its reduced transcriptional activity after
      blocking the generation of N1(IC) and its increased transcriptional activity in
      stable cells overexpressing N1(IC). ChIP and gel-shift assays revealed an
      interaction between a specific promoter region of ABCC1 and the N1(IC)-activated
      transcription factor CBF1, suggesting that the regulation of ABCC1 expression by
      Notch1 is mediated by CBF1. Indeed, deletion or site-directed mutagenesis of
      these CBF1 binding sites within the ABCC1 promoter region attenuated promoter
      reporter activity. Overall, our results reveal a unique regulatory mechanism of
      ABCC1 expression.

PMID- 22143793
TI  - Increased expression of histone demethylase JHDM1D under nutrient starvation
      suppresses tumor growth via down-regulating angiogenesis.
AB  - Histone demethylase JHDM1D (also known as KDM7A) modifies the level of
      methylation in histone and participates in epigenetic gene regulation; however,
      the role of JHDM1D in tumor progression is unknown. Here, we show that JHDM1D
      plays a tumor-suppressive role by regulating angiogenesis. Expression of JHDM1D
      was increased in mouse and human cancer cells under long-term nutrient starvation
      in vitro. Expression of JHDM1D mRNA was increased within avascular tumor tissue
      at the preangiogenic switch, along with increased expression of angiogenesis
      regulating genes such as Vegf-A. Stable expression of JHDM1D cDNA or siRNA
      silencing of JHDM1D in cancer cells did not affect cell proliferation, anchorage
      independent cell growth, or cell cycle progression in vitro. Notably, JHDM1D
      expressing mouse melanoma (B16) and human cervical carcinoma (HeLa) cells
      exhibited significantly slower tumor growth in vivo compared with the original
      cells. This reduction in tumor growth was associated with decreased formation of
      CD31(+) blood vessels and reduced infiltration of CD11b(+) macrophage linage
      cells into tumor tissues. Expression of multiple angiogenic factors such as VEGF
      B and angiopoietins was decreased in tumor xenografts of JHDM1D-expressing B16
      and HeLa cells. Our results provide evidence that increased JHDM1D expression
      suppressed tumor growth by down-regulating angiogenesis under nutrient
      starvation.

PMID- 22143794
TI  - Climate-associated phenological advances in bee pollinators and bee-pollinated
      plants.
AB  - The phenology of many ecological processes is modulated by temperature, making
      them potentially sensitive to climate change. Mutualistic interactions may be
      especially vulnerable because of the potential for phenological mismatching if
      the species involved do not respond similarly to changes in temperature. Here we
      present an analysis of climate-associated shifts in the phenology of wild bees,
      the most important pollinators worldwide, and compare these shifts to published
      studies of bee-pollinated plants over the same time period. We report that over
      the past 130 y, the phenology of 10 bee species from northeastern North America
      has advanced by a mean of 10.4 +/- 1.3 d. Most of this advance has taken place
      since 1970, paralleling global temperature increases. When the best available
      data are used to estimate analogous rates of advance for plants, these rates are
      not distinguishable from those of bees, suggesting that bee emergence is keeping
      pace with shifts in host-plant flowering, at least among the generalist species
      that we investigated.

PMID- 22143795
TI  - Effectiveness of international environmental regimes: existing knowledge, cutting
      edge themes, and research strategies.
AB  - International environmental regimes--especially those regimes articulated in
      multilateral environmental agreements--have been a subject of intense interest
      within the scientific community over the last three decades. However, there are
      substantial differences of opinion regarding the effectiveness of these
      governance systems or the degree to which they are successful in solving the
      problems leading to their creation. This article provides a critical review of
      the literature on this topic. It extracts and summarizes what is known about the
      effectiveness of environmental regimes in the form of a series of general and
      specific propositions. It identifies promising topics for consideration in the
      next phase of research in this field. Additionally, it comments on the research
      strategies available to pursue this line of analysis. The general conclusions are
      that international environmental regimes can and do make a difference, although
      often in conjunction with a number of other factors, and that a strategy of using
      a number of tools combined can help to improve understanding of the determinants
      of success.

PMID- 22143797
TI  - The unfolded protein response supports cellular robustness as a broad-spectrum
      compensatory pathway.
AB  - Stress pathways monitor intracellular systems and deploy a range of regulatory
      mechanisms in response to stress. One of the best-characterized pathways, the
      unfolded protein response (UPR), is responsible for maintaining endoplasmic
      reticulum (ER) homeostasis. The highly conserved Ire1 branch regulates hundreds
      of gene targets by activating a UPR-specific transcription factor. To understand
      how the UPR manages ER stress, a unique genetic approach was applied to reveal
      how the system corrects disequilibria. The data show that the UPR can address a
      wide range of dysfunctions that are otherwise lethal if not for its intervention.
      Transcriptional profiling of stress-alleviated cells shows that the program can
      be modulated, not just in signal amplitude, but also through differential target
      gene expression depending on the stress. The breadth of the functions mitigated
      by the UPR further supports its role as a major mechanism maintaining systems
      robustness.

PMID- 22143796
TI  - Dopamine stabilizes tumor blood vessels by up-regulating angiopoietin 1
      expression in pericytes and Kruppel-like factor-2 expression in tumor endothelial
      cells.
AB  - Impaired blood flow in the tumor vascular bed caused by structurally and
      functionally abnormal blood vessels not only hinders the delivery of
      chemotherapeutic agents but also aggravates tumor hypoxia, making the tumor cells
      further resistant to antineoplastic drugs. Therefore, normalization of tumor
      blood vessels may be an important approach to increase therapeutic efficacy in
      the treatment of cancer patients. As blood vessels are supplied by sympathetic
      nerves containing dopamine (DA), and DA regulates functions of normal blood
      vessels through its receptors present in these vessels, we investigated the
      effect of DA on tumor vasculature. Here we report loss of sympathetic innervation
      and endogenous DA in abnormal and immature tumor blood vessels in malignant colon
      and prostate tumor tissues. In contrast, exogenous administration of DA
      normalizes the morphology and improves the functions of these vessels by acting
      on pericytes and endothelial cells, the two major cellular components of blood
      vessels. DA acts through its D(2) receptors present in these cells to up-regulate
      directly the expression of angiopoietin 1 (Ang1) in pericytes and the expression
      of the zinc finger transcriptional factor, Kruppel-like factor-2 (KLF2) in tumor
      endothelial cells. Importantly, this vessel stabilization by DA also
      significantly increases the concentration of anticancer drug in tumor tissues.
      These results show a relationship between vascular stabilization and a
      neurotransmitter and indicate that DA or its D(2) receptor-specific agonists can
      be an option for the treatment of cancer and disorders in which normalization of
      blood vessels may have therapeutic benefits.

PMID- 22143798
TI  - Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2
      influenza viruses.
AB  - Seasonal epidemics caused by influenza virus are driven by antigenic changes
      (drift) in viral surface glycoproteins that allow evasion from preexisting
      humoral immunity. Antigenic drift is a feature of not only the hemagglutinin
      (HA), but also of neuraminidase (NA). We have evaluated the antigenic evolution
      of each protein in H1N1 and H3N2 viruses used in vaccine formulations during the
      last 15 y by analysis of HA and NA inhibition titers and antigenic cartography.
      As previously shown for HA, genetic changes in NA did not always lead to an
      antigenic change. The noncontinuous pattern of NA drift did not correspond
      closely with HA drift in either subtype. Although NA drift was demonstrated using
      ferret sera, we show that these changes also impact recognition by NA-inhibiting
      antibodies in human sera. Remarkably, a single point mutation in the NA of
      A/Brisbane/59/2007 was primarily responsible for the lack of inhibition by
      polyclonal antibodies specific for earlier strains. These data underscore the
      importance of NA inhibition testing to define antigenic drift when there are
      sequence changes in NA.

PMID- 22143799
TI  - Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1) inactivation
      is not reversed by restoring mitochondrial function.
AB  - Mammalian target of rapamycin complex 1 (mTORC1) is central to the control of
      cell, organ, and body size. Skeletal muscle-specific inactivation of mTORC1 in
      mice results in smaller muscle fibers, fewer mitochondria, increased glycogen
      stores, and a progressive myopathy that causes premature death. In mTORC1
      deficient muscles, peroxisome proliferator-activated receptor gamma coactivator 1
      alpha (PGC-1alpha), which regulates mitochondrial biogenesis and glucose
      homeostasis, is strongly down-regulated. Here we tested whether induction of
      mitochondrial biogenesis pharmacologically or by the overexpression of PGC-1alpha
      is sufficient to reverse the phenotype of mice deficient for mTORC1. We show that
      both approaches normalize mitochondrial function, such as oxidative capacity and
      expression of mitochondrial genes. However, they do not prevent or delay the
      progressive myopathy. In addition, we find that mTORC1 has a much stronger effect
      than PGC-1alpha on the glycogen content in muscle. This effect is based on the
      strong activation of PKB/Akt in mTORC1-deficient mice. We also show that
      activation of PKB/Akt not only affects glycogen synthesis but also diminishes
      glycogen degradation. Thus, our work provides strong functional evidence that
      mitochondrial dysfunction in mice with inactivated mTORC1 signaling is caused by
      the down-regulation of PGC-1alpha. However, our data also show that the
      impairment of mitochondria does not lead directly to the lethal myopathy.

PMID- 22143800
TI  - Fertilization with acrosome-reacted mouse sperm: implications for the site of
      exocytosis.

PMID- 22143801
TI  - PRDM1 is a tumor suppressor gene in natural killer cell malignancies.
AB  - Natural killer cell lymphoma (NKCL) constitutes a rare and aggressive form of non
      Hodgkin lymphoma, and there is little insight into its pathogenesis. Here we show
      that PRDM1 is a tumor suppressor gene in NKCLs that is inactivated by a
      combination of monoallelic deletion and promoter CpG island hypermethylation. We
      observed monoallelic deletion of PRDM1 loci in 8 of 18 (44%) NKCL cases. The
      other allele showed significant promoter methylation in 12 of 17 (71%) cases. In
      support of its role as a tumor suppressor gene, the reconstitution of PRDM1 in
      PRDM1-null NK cell lines led to G2/M cell cycle arrest, increased apoptosis, and
      a strong negative selection pressure with progressive elimination of PRDM1
      expressing cells, which was enhanced when IL-2 concentration is limiting. We
      observed a progressive increase in PRDM1 expression--in particular, PRDM1alpha-
      in normal NK cells in response to IL-2 and in normal NK cells activated with an
      engineered NK cell target, K562-Cl9-mb21, suggesting its role in NK cell
      homeostasis. In support of this role, knockdown of PRDM1 by shRNA in normal NK
      cells resulted in the positive selection of these cells. We identified MYC and 4
      1BBL as targets of PRDM1 in NK cells. Disruption of homeostatic control by PRDM1
      may be an important pathogenetic mechanism for NKCL.

PMID- 22143802
TI  - Ets transcription factor Pointed promotes the generation of intermediate neural
      progenitors in Drosophila larval brains.
AB  - Intermediate neural progenitor (INP) cells are transient amplifying neurogenic
      precursor cells generated from neural stem cells. Amplification of INPs
      significantly increases the number of neurons and glia produced from neural stem
      cells. In Drosophila larval brains, INPs are produced from type II neuroblasts
      (NBs, Drosophila neural stem cells), which lack the proneural protein Asense
      (Ase) but not from Ase-expressing type I NBs. To date, little is known about how
      Ase is suppressed in type II NBs and how the generation of INPs is controlled.
      Here we show that one isoform of the Ets transcription factor Pointed (Pnt),
      PntP1, is specifically expressed in type II NBs, immature INPs, and newly mature
      INPs in type II NB lineages. Partial loss of PntP1 in genetic mosaic clones or
      ectopic expression of the Pnt antagonist Yan, an Ets family transcriptional
      repressor, results in a reduction or elimination of INPs and ectopic expression
      of Ase in type II NBs. Conversely, ectopic expression of PntP1 in type I NBs
      suppresses Ase expression the NB and induces ectopic INP-like cells in a process
      that depends on the activity of the tumor suppressor Brain tumor. Our findings
      suggest that PntP1 is both necessary and sufficient for the suppression of Ase in
      type II NBs and the generation of INPs in Drosophila larval brains.

PMID- 22143804
TI  - Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation
      transporter-3.
AB  - The herbicide paraquat (PQ) has increasingly been reported in epidemiological
      studies to enhance the risk of developing Parkinson's disease (PD). Furthermore,
      case-control studies report that individuals with genetic variants in the
      dopamine transporter (DAT, SLC6A) have a higher PD risk when exposed to PQ.
      However, it remains a topic of debate whether PQ can enter dopamine (DA) neurons
      through DAT. We report here a mechanism by which PQ is transported by DAT: In its
      native divalent cation state, PQ(2+) is not a substrate for DAT; however, when
      converted to the monovalent cation PQ(+) by either a reducing agent or NADPH
      oxidase on microglia, it becomes a substrate for DAT and is accumulated in DA
      neurons, where it induces oxidative stress and cytotoxicity. Impaired DAT
      function in cultured cells and mutant mice significantly attenuated neurotoxicity
      induced by PQ(+). In addition to DAT, PQ(+) is also a substrate for the organic
      cation transporter 3 (Oct3, Slc22a3), which is abundantly expressed in non-DA
      cells in the nigrostriatal regions. In mice with Oct3 deficiency, enhanced
      striatal damage was detected after PQ treatment. This increased sensitivity
      likely results from reduced buffering capacity by non-DA cells, leading to more
      PQ(+) being available for uptake by DA neurons. This study provides a mechanism
      by which DAT and Oct3 modulate nigrostriatal damage induced by PQ(2+)/PQ(+) redox
      cycling.

PMID- 22143805
TI  - Polycomb group proteins are required to couple seed coat initiation to
      fertilization.
AB  - Seed development in flowering plants is initiated after a double fertilization
      event leading to the formation of zygotic embryo and endosperm tissues surrounded
      by the maternally derived seed coat. Although the seed coat does not take part in
      the fertilization process it develops immediately after fertilization,
      implicating a signaling mechanism from zygotic tissues to the surrounding
      maternal tissues. We addressed the question of the underlying mechanisms
      repressing seed coat development before fertilization and initiating seed coat
      development after fertilization by analyzing combinations of mutants that
      initiate seed development in the absence of fertilization. We discovered that
      seed coat development is actively repressed before fertilization by dosage
      sensitive Polycomb group proteins acting in maternal tissues surrounding the
      female gametophyte. This repression is relieved after fertilization by a signal
      that is formed by the sexual endosperm. Fertilization is required for signal
      formation, as asexually formed endosperm fails to effectively initiate seed coat
      development in mutants with uncompromised maternal Polycomb group function.
      Mutants for the MADS-box transcription factor AGL62 initiate embryo and endosperm
      formation but fail to develop a seed coat, implicating AGL62 expression in the
      endosperm as a requirement for signal initiation. Together, our results provide
      evidence that fertilization of the central cell generates a signal that relieves
      Polycomb group-mediated repression in the surrounding maternal tissues to
      initiate seed coat formation.

PMID- 22143806
TI  - Genetic variability and circulation pattern of human metapneumovirus isolated in
      Italy over five epidemic seasons.
AB  - Human metapneumovirus (hMPV) is an important aetiological agent of respiratory
      tract infection (RTI) in infants. Based on genetic differences, hMPVs are
      separated into two main groups, A and B, and two subgroups 1 and 2. To better
      understand the genetic diversity of hMPV, we analyzed 435 bp fragments of the F
      gene from 49 isolates obtained from a paediatric clinical centre in Northern
      Italy from 2005 to 2009. The phylogenetic analysis showed that our hMPV sequences
      clustered into five main clades (A1, A2a, A2b, B1, B2) statistically supported.
      Most of the strains belong to A2 (49%) and to B1 (28.5%) lineages. The
      intermixing in the phylogenetic tree showed no seasonal distribution between
      samples collected over a 5 year period. Mean genetic distances showed that clade
      A2 was more heterogeneous than others. In our F glycoprotein dataset we observed
      only two positively selected sites with an w value of 1.408 and 1.429,
      respectively, and 27 negatively selected sites. The two positively selected sites
      could be considered evolutionary "hot spots" because they were under positive
      selection and/or relaxed selective constraints. The abundant negatively selected
      sites reflect a high degree of conservation of F protein, probably necessary for
      viral infection.

PMID- 22143803
TI  - A small molecule differentiation inducer increases insulin production by
      pancreatic beta cells.
AB  - New drugs for preserving and restoring pancreatic beta-cell function are
      critically needed for the worldwide epidemic of type 2 diabetes and the cure for
      type 1 diabetes. We previously identified a family of neurogenic 3,5
      disubstituted isoxazoles (Isx) that increased expression of neurogenic
      differentiation 1 (NeuroD1, also known as BETA2); this transcription factor
      functions in neuronal and pancreatic beta-cell differentiation and is essential
      for insulin gene transcription. Here, we probed effects of Isx on human cadaveric
      islets and MIN6 pancreatic beta cells. Isx increased the expression and secretion
      of insulin in islets that made little insulin after prolonged ex vivo culture and
      increased expression of neurogenic differentiation 1 and other regulators of
      islet differentiation and insulin gene transcription. Within the first few hours
      of exposure, Isx caused biphasic activation of ERK1/2 and increased bulk histone
      acetylation. Although there was little effect on histone deacetylase activity,
      Isx increased histone acetyl transferase activity in nuclear extracts.
      Reconstitution assays indicated that Isx increased the activity of the histone
      acetyl transferase p300 through an ERK1/2-dependent mechanism. In summary, we
      have identified a small molecule with antidiabetic activity, providing a tool for
      exploring islet function and a possible lead for therapeutic intervention in
      diabetes.

PMID- 22143807
TI  - Neutralization by human serum samples of a transmissible agent isolated from the
      cerebrospinal fluid of neurological patients.
AB  - A transmissible cytotoxic agent thought to be associated with one or more
      misfolded protein(s) was found in several cerebrospinal fluid (CSF) samples from
      neurological patients. Since some experiments carried out to identify this
      unusual infectious factor showed the block of its propagation by rabbit
      gammaglobulins (IgGs), the search for such an activity by human IgGs was
      programmed. Neutralizing assays carried out using human sera as IgGs source
      showed a blocking property displayed by: twenty serum samples from as many
      patients with a diagnosis of acute infection, two of ten sera from healthy
      subjects and four serum samples from patients with lupus erythematous (SLE). When
      neutralizing sera were tested on cell cultures in immunofluorescence assays for
      the serum ability to label specific protein( s), similar fluorescent pictures
      resulted in treated and control cells. On the other hand, the SLE serum samples
      disclosed a granulosity of the nuclear material of cytotoxic cells in accordance
      with the DNA apoptotic laddering reported in previous papers. Oxidative
      disorders, as suggested by the immunoblotting analysis of the antioxidant enzymes
      Mn-superoxide dismutase (SOD2) and heme-oxygenase 1 (HO-1), point to an
      alteration of the oxidative pathway among the causes of the DNA damage induced by
      the cytotoxic transmissible agent under study.

PMID- 22143808
TI  - Evaluation of performance of quantiferon assay and tuberculin skin test in end
      stage renal disease patients receiving hemodialysis.
AB  - PURPOSE: End stage renal disease (ESRD) cases are associated with increased risk
      of tuberculosis. There is no gold standard method for detecting latent
      tuberculosis infection (LTBI) in ESRD. The aim of the present study was to
      analyze the performance of the tuberculin skin test (TST) and QuantiFERON-TB Gold
      in tube (QFT-G) in cases receiving hemodialysis (HD). METHODS: The TST and QFT-G
      were prospectively performed in 96 ESRD cases undergoing HD. The agreement of the
      QFT-G and TST was assessed in two TST cut off values (10 mm and 5 mm) in Bacille
      Calmette Guerin (BCG) vaccinated and non-vaccinated cases. RESULTS: Of 96 cases
      67 were BCG vaccinated and 29 were BCG non-vaccinated. QFT-G was positive in
      39.6% cases and indeterminate in 3.1%. TST was positive in 43.8% of cases in cut
      off value of 10 mm and positive in 58.3% of cases in cut off value of 5 mm.
      Agreement between TST and QFT-G results was fair in both BCG vaccinated and non
      vaccinated cases in either cut off values, except in cut off value of 10 mm in
      BCG vaccinated cases in which the agreement was moderate. CONCLUSION: The
      agreement between QFT-G and TST test is fair and there is no significant
      difference in both cut off values of TST in screening of LTBI in ESRD cases
      receiving HD.

PMID- 22143809
TI  - Bacteriocin production and resistance to drugs are advantageous features for
      Lactobacillus acidophilus La-14, a potential probiotic strain.
AB  - L. acidophilus La-14 produces bacteriocin active against L. monocytogenes ScottA
      (1600 AU/ml) in MRS broth at 30 degrees C or 37 degrees C. The bacteriocin proved
      inhibitory to different serological types of Listeria spp. Antimicrobial activity
      was completely lost after treatment of the cell-free supernatant with proteolytic
      enzymes. Addition of bacteriocin produced by L. acidophilus La-14 to a 3 h-old
      culture of L. monocytogenes ScottA repressed cell growth in the following 8h.
      Treatment of stationary phase cells of L. monocytogenes ScottA (107-108 CFU/ml)
      by the bacteriocin resulted in growth inhibition. Growth of L. acidophilus La-14
      was not inhibited by commercial drugs from different generic groups, including
      nonsteroidal anti-inflammatory drugs (NSAID) containing diclofenac potassium or
      ibuprofen arginine. Only one non-antibiotic drug tested, Atlansil (an
      antiarrhythmic agent), had an inhibitory effect on L. acidophilus La-14 with MIC
      of 2.5 mg/ml. L. acidophilus La-14 was not affected by drugs containing sodium or
      potassium diclofenac. L. acidophilus La-14 shows a good resistance to several
      drugs and may be applied in combination for therapeutic use.

PMID- 22143810
TI  - First detection of OKP-A beta-lactamase in two Serratia marcescens isolates in
      China.
AB  - Two strains of Enterobacteriaceae producing prodigiosin were isolated from meat
      in the Sichuan province of China in 2010. The strains were identified by Vitek
      system, 16S rDNA, rpoB, pfs and luxS genes. Minimum inhibitory concentrations
      were determined using the broth microdilution method. The two strains were
      screened for the presence of beta-lactamase genes (blaTEM, blaSHV, blaOKP, and
      blaCTX-M genes). Based on PCR amplification and 16S rDNA sequencing the analysed
      strains were identified as Serratia marcescens. In addition, morphological and
      biochemical identification showed that the two stains were definitely S.
      marcesens. Antimicrobial susceptibility test showed that both strains were
      resistant to ampicillin and first-generation cephalosporins while being
      susceptible to cefotaxime, ceftiofur, ceftriaxone, imipenem and aztreonam. It was
      found that blaOKP had been identified first from the two S. marcescens strains,
      ch1 and ch2. The isolates were closely related as shown by pulsed-field gel
      electrophoresis (PFGE). The narrow-spectrum OKP-A beta-lactamase gene blaOKP-A-13
      was found to be chromosomally located in S. marcescens. The isolates produced a
      beta-lactamase with a pI of approximately 8.2, which corresponds to the OKPA
      family. Findings indicate that OKP enzymes are not Klebsiella pneumoniae-specific
      chromosomal ?-lactamases, and the first isolation of S. marcescens producing OKP
      A ?-lactamase suggests that the blaOKP gene may be disseminated between different
      species.

PMID- 22143811
TI  - Oral candidosis: characterization of a sample of recurrent infections and study
      of resistance determinants.
AB  - Recurrent oral candidosis is a common problem in immunocompromised patients, and
      it is frequently triggered by resistance induced by antifungal treatment.
      Knowledge of the mechanisms by which the yeast persists in the host could allow
      the management of this type of infection. This study used electrophoretic
      karyotyping and restriction fragment length polymorphism based on the use of 27A
      probe to study 12 pairs of Candida albicans isolates from patients with recurrent
      candidosis to distinguish new infections from relapses caused by the same strain
      responsible for the first episode. Subsequently, RT-PCR was used to evaluate
      expression of CDR1, CDR2 and MDR1 genes, which are involved in C. albicans azole
      resistance, in the three pairs that consisted of variants of the same strain.
      Restriction polymorphism resulted in better discrimination than with karyotyping
      in defining differences between strains. In one case, RT-PCR allowed us to
      identify deregulation of efflux pump genes as the possible underlying mechanism
      in recurrent candidosis. The techniques employed resulted effective for the
      characterization of recurrent oral candidosis. Broader analysis could help to
      control better these infections and choose adequate therapy.

PMID- 22143812
TI  - Assembly and characterization of pandemic influenza A H1N1 genome in
      nasopharyngeal swabs using high-throughput pyrosequencing.
AB  - De novo high-throughput pyrosequencing was used to detect and characterize 2009
      pandemic influenza A (H1N1) virus directly in nasopharyngeal swabs in the context
      of the microbial community. Data were generated with a prior sequence independent
      amplification by 454 pyrosequencing on GS-FLX platform (Roche). Influenza A
      assembled reads allowed near full-length genome reconstruction with the
      simultaneous analysis of site-specific heterogeneity. The molecular approach
      applied proved to be a powerful tool to characterize the new pandemic H1N1
      influenza virus in clinical samples. This approach could be of great value in
      identifying possibly new reassortants that may occur in the near future.

PMID- 22143813
TI  - Molecular analysis of relapses or reinfections of Clostridium difficile
      associated diarrhea.
AB  - Recurrence is a major complication of Clostridium difficile-associated diarrhea
      and occurs in 15 to 20% of patients after discontinuation of therapy. Strains
      from 53 patients with Clostridium difficile recurrences were fingerprinted by PCR
      ribotyping. Reinfection with a different strain occurred in 15 out of 53 patients
      (28,3%), while 38 patients relapsed. These data suggest the need to perform
      molecular typing for implementation of infection control procedures and for a
      more appropriate therapeutic strategy.

PMID- 22143814
TI  - Antibiotic sensitivity of bacterial isolates from cases of canine dermatitis.
AB  - Among 97 bacterial isolates, 74 strains of Staphylococcus spp developed from 95
      swabs taken from skin lesions in dogs. Twenty-eight staphylococcal strains
      resistant to methicillin and/or oxacillin were identified and mecA expression was
      confirmed for 14 of these strains. S. aureus and S. intermedius group (SIG)
      strains were particularly relevant in our cases due to their antibiotic
      resistance leading to an increased veterinary and public health risk. We suggest
      a diagnostic protocol based on cytological examination, bacterial identification
      to species level, and antibiotic sensitivity testing prior to prescribing
      antibiotic treatment for canine skin diseases.

PMID- 22143815
TI  - Serological and pathogenic characterization of Erysipelothrix rhusiopathiae
      isolates from two human cases of endocarditis in Japan.
AB  - We characterized the serological and pathogenic properties of two Erysipelothrix
      rhusiopathiae isolates from human cases of infective endocarditis in Japan. One
      isolate was recovered from a fisherman, and was identified as serovar 3, which is
      known to be prevalent among fish isolates. This strain exhibited high virulence
      in mice but was avirulent in swine. Another was untypable, and avirulent in both
      mice and swine. Our results suggest that various serological and athogenical
      types of E. rhusiopathiae can induce human endocarditis. This is the first report
      to characterize the pathogenicity of E. rhusiopathiae isolates from human
      endocarditis.

PMID- 22143816
TI  - An atypical strain associated with congenital toxoplasmosis in Tunisia.
AB  - We report the identification and typing of a congenital toxoplasmosis case in a
      diabetic pregnant young woman living in Tunis. The Toxoplasma DNA extracted from
      amniotic fluid was detected by Real Time PCR and subjected to a multilocus
      genetic characterisation of the strain at markers: 3'SAG2, 5'SAG2, New SAG2,
      SAG3, GRA6, BTUB, APICO, PK1, KT850 and UPRT1. An atypical genotype of T.gondii
      with unusual genetic composition was revealed. It is the first time that an
      atypical strain has been associated with congenital toxoplasmosis in Africa.
      Atypical strains are associated with severe clinical manifestations so systematic
      genotyping should be investigated with the amniocentesis.

PMID- 22143817
TI  - 23-valent pneumococcal vaccine failure in a patient who developed pneumonia: a
      case report.
AB  - We report a clinical failure of a pneumococcal vaccine in a patient who developed
      pneumococcal pneumonia. In 2008, an 85-year-old Italian woman was admitted to the
      Respiratory Disease Unit of a hospital in Southern Italy. The 23-valent
      pneumococcal vaccine had been administered to the patient 50 days earlier. The
      chest x-ray disclosed a right basal bronchopneumonic focus. Streptococcus
      Pneumoniae serotype 19A, a strain included in the 23-valent pneumococcal vaccine,
      was isolated from the sputum. There is a need for more efficacious conjugated
      vaccines covering the majority of the pneumococcal serotypes that cause serious
      illness in older children and adults worldwide.

PMID- 22143818
TI  - Coronary involvement  in Mediterranean spotted fever.
AB  - Mediterranean spotted fever (MSF) is a tick-borne acute febrile disease caused by
      Rickettsia conorii and characterized by fever, a maculo-papular rash and a black
      eschar at the site of the tick bite. We describe the case of a 3-year-old boy
      with MSF who developed a transient right coronary artery ectasia. The patient was
      brought to the hospital after four days of fever and mild myalgia of the legs.
      The suspicion of MSF arose due to the presence of a maculo-papular skin rash and
      treatment with oral clarithromycin was started. After four days fever persisted
      and the differential diagnosis of Kawasaki syndrome was considered.
      Echocardiography showed a dilated right coronary artery with hyperreflective
      walls. Treatment with intravenous immunoglobulin was initiated while
      clarithromycin was continued. After one day the fever disappeared. An
      immunofluorescent antibody test performed after four weeks confirmed a R. conorii
      infection. A follow-up echocardiography was normal six weeks and six months
      later. We suggest that ectasia of the coronary arteries may be a manifestation of
      rickettsial vasculitis. Prospective studies are needed to understand the
      frequency and the possible consequences of this phenomenon in the course of MSF.

PMID- 22143819
TI  - Wound infection by multiresistant Staphylococcus sciuri identified by molecular
      methods.
AB  - We describe a case of wound infection by multidrug-resistant Staphylococcus
      sciuri in a patient admitted to hospital for injuries in Agreste Alagoas, Brazil,
      identified through broad-spectrum PCR and sequencing of 16S rDNA gene. Due to its
      high resistance profile, the infection was characterized as methicillin-resistant
      Staphylococcus presenting sensitive only to vancomycin and chloramphenicol. The
      injury resulting from trauma associated with infection resulted in amputation of
      the infected limb.

PMID- 22143820
TI  - Chromobacterium violaceum lymphadenitis successfully treated in a Northern
      Italian hospital.
AB  - Lymphadenitis can be caused by different gram positive and gram negative bacteria
      and non-tuberculous mycobacteria. Cervical lymphadenitis in children is thought
      to result from ingestion of or contact with environmental microrganisms.
      Chromobacterium violaceum is a common inhabitant of soil and water in tropical
      and sub tropical countries. In these parts of the world Chromobacterium violaceum
      is able to cause skin infection with diffuse pustular lesions and also multiple
      liver abscess with often fatal evolution in sepsis. We describe a case of
      cervical lymphadenitis caused by Chromobacterium violaceum in a 14-year-old boy,
      born in Guinea and resident in Italy for 7 years in a fair condition with general
      measurable swelling in the right lateral cervical region and with blood tests
      that showed increased inflammatory indices. The patient was subjected to surgical
      incision. Antibiotic therapy with ceftriaxone was continued for 10 days, then
      replaced successfully with oral ciprofloxacin on the basis of purulent material
      culture positive for Chromobacterium violaceum sensitive to fluoroquinolones.

PMID- 22143821
TI  - Parental prenatal smoking and risk of childhood acute lymphoblastic leukemia.
AB  - The association between parental smoking and risk of childhood acute
      lymphoblastic leukemia (ALL) was investigated in an Australian population-based
      case-control study that included 388 cases and 868 controls aged <15 years,
      recruited from 2003 to 2006. Both of the child's parents provided information
      about their smoking habits for each year from age 15 years to the child's birth.
      Data were analyzed by logistic regression. Maternal smoking was not associated
      with risk of childhood ALL, but the odds ratio for paternal smoking of >=15
      cigarettes per day around the time of the child's conception was 1.35 (95%
      confidence interval: 0.98, 1.86). The associations between parental smoking risk
      of childhood ALL did not differ substantially by immunophenotypic or cytogenetic
      subtype. Meta-analyses of paternal smoking, including results from the Australian
      Study of Causes of Acute Lymphoblastic Leukemia in Children and those of previous
      studies, produced summary odds ratios of 1.15 (95% confidence interval: 1.06,
      1.24) for any paternal smoking around the time of the child's conception and 1.44
      (95% confidence interval: 1.24, 1.68) for smoking >=20 cigarettes per day at that
      time. Study results suggest that heavier paternal smoking around the time of
      conception is a risk factor for childhood ALL. Men should be strongly encouraged
      to cease smoking, particularly when planning to start a family.

PMID- 22143822
TI  - Prevention of age-associated neurodegeneration and promotion of healthy brain
      ageing in female Wistar rats by long term use of bacosides.
AB  - Bacopa monnieri (L.), popularly known as Brahmi, is a revered Ayurvedic medicinal
      plant used as nerve tonic since time immemorial. The present study aims to
      investigate the neuroprotective effect of bacosides, the active saponins of
      Bacopa monnieri (L.) against age associated neurodegeneration and its impact over
      the prevention of Senile Dementia of Alzheimer's Type (SDAT). The optimum dose of
      bacosides with no adverse effect was selected by screening its dose dependant
      activity on ageing biomarker lipofuscin and SDAT biomarker neurotransmitter
      acetylcholine in the aged female Wistar rat brain. The selected therapeutic dose
      of bacosides (200 mg/kg) was orally administered for 3 months in middle aged and
      aged rats and further investigated for its protective action against age
      associated alterations in neurotransmission system, behavioral paradigms,
      hippocampal neuronal loss and oxidative stress markers. The results of the
      present study suggest that bacosides may act as a potential therapeutic
      intervention in forestalling the deleterious effects of ageing and preventing the
      age associated pathologies like SDAT.

PMID- 22143823
TI  - Human Xp/Yp telomere analysis by Southern-STELA.
AB  - Telomeres are specialized structures designed to protect the ends of linear
      chromosomes. They are dynamic structures such that in normal somatic cells they
      constantly shorten as cell division progresses. There is compelling evidence that
      telomere shortening leads to cell senescence, a process perceived as the main
      cause of aging in higher mammals. Therefore, the features of telomere shortening
      are of great importance in understanding cell senescence and aging in general. By
      identifying unique subtelomeric regions, large enough to produce strong
      chemiluminescent signals, we have provided a new tool for Southern blot analysis
      of individual human Xp/Yp telomeres. We extend these results with quantitative
      fluorescence in situ hybridization using peptide nucleic acid probe (PNA Q-FISH)
      analysis of telomeres on the Y chromosome. Our results demonstrates unequal
      shortening dynamics between the p and q telomeres.

PMID- 22143824
TI  - p-Chloro-diphenyl diselenide, an organoselenium compound, with antidepressant
      like and memory enhancer actions in aging male rats.
AB  - The aim of this study was to evaluate the protective effects of p-chloro-diphenyl
      diselenide (p-ClPhSe)(2) on depressant-like action and cognitive impairment
      caused by aging in male rats. For this purpose, old rats were orally treated with
      (p-ClPhSe)(2) (10 or 25 mg/kg) for seven days. Then, rats were tested in
      experimental models of ambulation, memory and depression. In addition, Na(+) K(+)
      ATPase activity and reactive species (RS) levels were measured in rat cortex and
      hippocampus. Our findings demonstrated that treatment of old rats with (p
      ClPhSe)(2) (10 and 25 mg/kg) reversed spatial memory deficit in the object
      location test and depressant-like action in the forced swimming test (FST) caused
      by aging. Reduction in exploratory behavior (rearings) in the open-field test
      caused by aging was not altered by (p-ClPhSe)(2) administration. Moreover, the
      increase of RS levels and inhibition of Na(+) K(+) ATPase activity in cortex and
      hippocampus resulting from aging were restored by the highest dose of (p
      ClPhSe)(2). To assess the mechanisms involved in the antidepressant-like effect
      of (p-ClPhSe)(2), old rats received WAY100635 (0.1 mg/kg, subcutaneous, a
      selective 5-HT(1A)R antagonist), ritanserin (1 mg/kg, intraperitoneal, a 5
      HT(2A/2C)R antagonist) or ondansetron (1 mg/kg, intraperitoneal, a 5-HT(3)R
      antagonist) 15 min before (p-ClPhSe)(2) (25 mg/kg) treatment. After 30 min, the
      FST was performed. Results showed that in addition to the antioxidant action, the
      modulation of 5-HT(1A) and 5-HT(3) receptors may be at least partly involved in
      the antidepressant-like action elicited by (p-ClPhSe)(2) in old rats. These
      findings highlight the beneficial potential of (p-ClPhSe)(2) in aged male rats.

PMID- 22143826
TI  - Failure of policy regarding smoke-free bars in the Netherlands.
AB  - BACKGROUND: Tobacco companies consistently work to prevent and undermine smoke
      free laws. The tobacco industry and its allies have funded hospitality
      associations and other third parties to oppose smoke-free laws, argue that smoke
      free laws will economically damage hospitality venues, promote ventilation and
      voluntary smoker 'accommodation' as an alternative to smoke-free laws, and to
      challenge smoke-free laws in court. In 2008, the Netherlands extended its smoke
      free law to hospitality venues. METHODS: We triangulated news articles,
      government documents, scientific papers, statistical reports and interviews to
      construct this case study. RESULTS: Despite widespread public support for smoke
      free hospitality venues, opponents successfully represented these laws as
      unpopular and damaging to small bars. These challenges and related smokers'
      rights activities resulted in non-compliance among all bars and reinstating an
      exemption for small, owner-run venues. This policy reversal was the result of a
      weak implementing media campaign (which failed to present the law as protecting
      nonsmokers), smoking room exemptions and reactive (vs. proactive) measures by the
      Ministry of Health and civil society. CONCLUSION: The policy failure in the
      Netherlands is the result of poor implementation efforts and the failure to
      anticipate and deal with opposition to the law. When implementing smoke-free laws
      it is important to anticipate opposition, used the media to target non-smokers to
      reinforce public support, and actively enforce the law.

PMID- 22143828
TI  - Adrenal disease update 2011.
AB  - This article is based on an invited lecture entitled "Year-in-the-Adrenal: A
      Clinical Perspective," presented at the 92nd Annual Meeting of The Endocrine
      Society in Boston, Massachusetts, on June 7, 2011. The objective was to provide
      clinicians with a summary of key, clinically important advances in the field of
      adrenal disorders over the past 18 months. Paper selection was based on a
      comprehensive survey of all adrenal articles published in major endocrinology and
      high-impact general medical journals between December 2009 and May 2011.
      Participants in the selection process included 15 endocrinologists with expertise
      in adrenal disorders. The articles highlighted were those that: 1) constitute
      novel discoveries that may improve the understanding of pathophysiology; 2)
      address important clinical questions; and 3) most influence the way we diagnose
      and treat patients with adrenal disorders. An effort was made to include both
      adrenal cortical and medullary disorders.

PMID- 22143830
TI  - The importance of whole body imaging in tumor-induced osteomalacia.

PMID- 22143829
TI  - Approach to the patient with gestational diabetes after delivery.
AB  - The diagnosis of gestational diabetes mellitus (GDM) identifies patients with a
      pancreatic beta-cell defect. In some patients, the defect is transient or stable,
      but in most it is progressive, imparting a high risk of diabetes for at least a
      decade after the index pregnancy. The beta-cell defects in GDM can result from
      many causes, including genetic variants typical of monogenic forms of diabetes
      and autoimmunity typical of evolving type 1 diabetes. No specific disease
      modifying therapies are available for those patients. The majority of women with
      GDM have clinical characteristics indicating a risk for type 2 diabetes (T2D).
      Available evidence indicates that T2D can be prevented or delayed by intensive
      lifestyle modification and by medications, particularly those that ameliorate
      insulin resistance. Clinical management should include assessment of glucose
      tolerance in the postpartum period to detect diabetes or assess diabetes risk.
      Women who don't have diabetes should be advised about their risk and participate
      in family planning to prevent subsequent pregnancies with undiagnosed
      hyperglycemia. All patients should be monitored for rising glycemia indicative of
      progressive beta-cell deterioration. We suggest a combination of fasting glucose
      and glycosylated hemoglobin measurements for this purpose. Monitoring should be
      initiated at least annually and should be intensified if glycemia is rising
      and/or impaired. Lifestyle modification is advised to reduce the risk for T2D.
      Like monitoring, lifestyle modification should be intensified for rising glycemia
      and/or development of impaired glucose levels. At present, there is insufficient
      evidence to recommend medications to prevent T2D. Close follow-up and monitoring
      will allow initiation of pharmacological treatment as soon as diabetes develops.
      Children of women with GDM are at increased risk for obesity and diabetes. They
      should receive education, monitoring, and lifestyle advice to minimize obesity
      and diabetes risk.

PMID- 22143831
TI  - Paroxysmal thyroid swelling. A forgotten clinical finding of pheochromocytoma.

PMID- 22143832
TI  - The battered beta-cell: usual suspects and guilt by association.

PMID- 22143833
TI  - Uncertainty remains in women with PCOS regarding the increased incidence of
      cardiovascular disease later in life, despite the indisputable presence of
      multiple cardiovascular risk factors at a young age.

PMID- 22143839
TI  - Patient information page from The Hormone Foundation. Growth hormone deficiency
      in children.

PMID- 22143841
TI  - Cardiac remodeling and function following exercise and angiotensin II receptor
      antagonism.
AB  - The purpose of this study was to test the impact of chronic exercise training
      combined with selective angiotensin II receptor (AT1) antagonism on systolic
      blood pressure (SBP) and the left-ventricular pressure-volume relationship in
      normotensive, non-infarcted rat hearts. Wistar rats (N = 19) were randomly
      assigned to either a sedentary control group (N = 8) or an exercise-trained group
      (N = 11). Losartan was administered to individually caged rats via the drinking
      water (10 mg/kg/d). Exercise training consisted of running on a motorized driven
      treadmill for 6 weeks at 30 m/min, 60 min/day, 5 days/week. Tail cuff SBP was
      measured weekly. Left ventricular performance was assessed in an ex vivo
      Langendorff isovolumic mode. One week of losartan treatment significantly reduced
      SBP in both groups by 13% relative to baseline (P < 0.05). SBP was lower in
      exercise-trained animals versus sedentary animals in the later weeks of the
      protocol (P < 0.05) Body weight was significantly lower in exercise-trained
      animals versus sedentary animals, but heart weight, heart to body weight ratio,
      atrial weight, and absolute left ventricular mass and length were similar between
      groups. The LV systolic pressure-volume relationship (PV) and systolic elastance
      were significantly greater in exercise-trained animals versus sedentary controls
      (P < 0.05). The left ventricular end-diastolic PV and diastolic stiffness were
      similar between exercise-trained and sedentary animals. These data suggest that
      chronic aerobic exercise training can improve the Starling response in the
      presence of AT1 receptor blockade without altering absolute cardiac size.

PMID- 22143842
TI  - Influence of mental workload on muscle endurance, fatigue, and recovery during
      intermittent static work.
AB  - Most occupational tasks involve some level of mental/cognitive processing in
      addition to physical work; however, the etiology of work-related musculoskeletal
      disorders (WMSDs) due to these demands remains unclear. The aim of this study was
      to quantify the interactive effects of physical and mental workload on muscle
      endurance, fatigue, and recovery during intermittent work. Twelve participants,
      balanced by gender, performed intermittent static shoulder abductions to
      exhaustion at 15, 35, and 55% of individual maximal voluntary contraction (MVC),
      in the absence (control) and presence (concurrent) of a mental arithmetic task.
      Changes in muscular capacity were determined using endurance time, strength
      decline, electromyographic (EMG) fatigue indicators, muscle oxygenation, and
      heart rate measures. Muscular recovery was quantified through changes in strength
      and physiological responses. Mental workload was associated with shorter
      endurance times, specifically at 35% MVC, and greater strength decline. EMG and
      oxygenation measures showed similar changes during fatigue manifestation during
      concurrent conditions compared to the control, despite shorter endurance times.
      Moreover, decreased heart rate variability during concurrent demand conditions
      indicated increased mental stress. Although strength recovery was not influenced
      by mental workload, a slower heart rate recovery was observed after concurrent
      demand conditions. The findings from this study provide fundamental evidence that
      physical capacity (fatigability and recovery) is adversely affected by mental
      workload. Thus, it is critical to determine or evaluate occupational demands
      based on modified muscular capacity (due to mental workload) to reduce risk of
      WMSD development.

PMID- 22143843
TI  - Effects of cuff width on arterial occlusion: implications for blood flow
      restricted exercise.
AB  - The purpose of this study was to determine the difference in cuff pressure which
      occludes arterial blood flow for two different types of cuffs which are commonly
      used in blood flow restriction (BFR) research. Another purpose of the study was
      to determine what factors (i.e., leg size, blood pressure, and limb composition)
      should be accounted for when prescribing the restriction cuff pressure for this
      technique. One hundred and sixteen (53 males, 63 females) subjects visited the
      laboratory for one session of testing. Mid-thigh muscle (mCSA) and fat (fCSA)
      cross-sectional area of the right thigh were assessed using peripheral
      quantitative computed tomography. Following the mid-thigh scan, measurements of
      leg circumference, ankle brachial index, and brachial blood pressure were
      obtained. Finally, in a randomized order, arterial occlusion pressure was
      determined using both narrow and wide restriction cuffs applied to the most
      proximal portion of each leg. Significant differences were observed between cuff
      type and arterial occlusion (narrow: 235 (42) mmHg vs. wide: 144 (17) mmHg; p =
      0.001, Cohen's D = 2.52). Thigh circumference or mCSA/fCSA with ankle blood
      pressure, and diastolic blood pressure, explained the most variance in the cuff
      pressure required to occlude arterial flow. Wide BFR cuffs restrict arterial
      blood flow at a lower pressure than narrow BFR cuffs, suggesting that future
      studies account for the width of the cuff used. In addition, we have outlined
      models which indicate that restrictive cuff pressures should be largely based on
      thigh circumference and not on pressures previously used in the literature.

PMID- 22143844
TI  - A fractionation of the physiological burden of the personal protective equipment
      worn by firefighters.
AB  - Load carriage increases physiological strain, reduces work capacity and elevates
      the risk of work-related injury. In this project, the separate and combined
      physiological consequences of wearing the personal protective equipment used by
      firefighters were evaluated. The overall impact upon performance was first
      measured in 20 subjects during a maximal, job-related obstacle course trial and
      an incremental treadmill test to exhaustion (with and without protective
      equipment). The fractional contributions of the thermal protective clothing,
      helmet, breathing apparatus and boots were then separately determined during
      steady-state walking (4.8 km h(-1), 0% gradient) and bench stepping (20 cm at 40
      steps min(-1)). The protective equipment reduced exercise tolerance by 56% on a
      treadmill, with the ambulatory oxygen consumption reserve (peak minus steady
      state walking) being 31% lower. For the obstacle course, performance declined by
      27%. Under steady-state conditions, the footwear exerted the greatest relative
      metabolic impact during walking and bench stepping, being 8.7 and 6.4 times
      greater per unit mass than the breathing apparatus. Indeed, the relative
      influence of the clothing on oxygen cost was at least three times that of the
      breathing apparatus. Therefore, the most efficient way to reduce the
      physiological burden of firefighters' protective equipment, and thereby increase
      safety, would be to reduce the mass of the boots and thermal protective clothing.

PMID- 22143845
TI  - Validation of the SenseWear armband in circuit resistance training with different
      loads.
AB  - The use of the SenseWearTM armband (SWA), an objective monitor of physical
      activity, is a relatively new device used by researchers to measure energy
      expenditure. These monitors are practical, relatively inexpensive and easy-to
      use. The aim of the present study was to assess the validity of SWAs for the
      measurement of energy expenditure (EE) in circuit resistance training (CRT) at
      three different intensities in moderately active, healthy subjects. The study
      subjects (17 females, 12 males) undertook CRT at 30, 50 and 70% of the 15
      repetition maximum for each exercise component wearing an SWA as well as an
      Oxycon Mobile (OM) portable metabolic system (a gold standard method for
      measuring EE). The EE rose as exercise intensity increased, but was
      underestimated by the SWAs. For women, Bland-Altman plots showed a bias of 1.13
      +/- 1.48 METs and 32.1 +/- 34.0 kcal in favour of the OM system, while for men
      values of 2.33 +/- 1.82 METs and 75.8 +/- 50.8 kcal were recorded.

PMID- 22143847
TI  - Sarcoma services in New Zealand.

PMID- 22143848
TI  - Why is publicly funded bariatric surgery still not fully supported?

PMID- 22143846
TI  - Oxidative damage is present in plasma and circulating neutrophils 4 weeks after a
      high mountain expedition.
AB  - It is well known that exposure to extreme environments, such as in high-mountain
      expeditions, is associated with increased production of reactive oxygen species
      and related oxidative damage. However, there is little information concerning
      antioxidant recovery after this type of expedition. Thus, the aim of this study
      is to analyze the antioxidant recovery status at sea level of five expert
      alpinists 4 weeks after climbing Cho-Oyu (8,201 m). Body composition,
      cardiorespiratory capacity, and circulating parameters were almost similar to the
      values obtained at the beginning of the study. However, the alpinists presented
      high erythrocyte number, related hemogram values, and ferritin. Sodium, alkaline
      phosphatase, and gamma-glutamyltransferase plasma levels were lower. Concerning
      oxidative stress, plasma uric acid levels were significantly increased, as well
      as malondialdehyde and protein carbonyls. Neutrophils displayed significantly
      higher levels of malondialdehyde and lower catalase activity. Therefore, these
      data indicate that the oxidative stress during a high mountain expedition is the
      most probable cause to explain an incomplete recovery in plasma and neutrophil
      antioxidant status.

PMID- 22143849
TI  - Access to new medicines in New Zealand compared to Australia.
AB  - AIM: To compare access to new prescription-only medicines in New Zealand (NZ)
      with that in Australia. METHOD: The range of new prescription medicines and the
      timing of their regulatory approval and reimbursement in NZ and Australia in the
      period 2000 to 2009 were compared. RESULTS: 136 new prescription medicines were
      first listed in the Australian Schedule of Pharmaceutical Benefits in the study
      period and 59 (43%) of these were listed in the NZ Pharmaceutical Schedule.
      Listing of these 59 medicines for reimbursement occurred later in NZ (mean
      difference=32.7 months; 95% CI 24.2 to 41.2 months; p<0.0001) due largely to a
      longer time from registration to listing (mean difference=23.7 months; 95% CI
      14.9 to 32.4 months; p<0.0001). The remaining 77 medicines that are reimbursed in
      Australia but not in NZ cover a wide range of therapeutic areas, including some
      diseases for which there are no reimbursed medicines in NZ. Four new medicines
      were listed in NZ but not Australia. CONCLUSION: In the last decade, public
      access to new medicines in NZ has been more limited and delayed compared to
      Australia.

PMID- 22143850
TI  - Over-the-counter codeine analgesic misuse and harm: characteristics of cases in
      Australia and New Zealand.
AB  - AIM: To describe the characteristics of clients addicted to over-the-counter
      (OTC) codeine analgesics presenting to an Auckland open-access clinic, and to
      compare them to clients admitted to a New Zealand detoxification unit, and in the
      Australian community. METHOD: Cross-sectional study of clients presenting to a
      regional, open-access detoxification clinic covering the Greater Auckland area
      between 1 January and 31 March 2010. RESULTS: Fifteen clients were analysed, and
      compared to 77 similar clients identified in Victoria and five other Australian
      States, and 7 clients admitted to a New Zealand detoxification unit. Cases in
      each cohort were consistent with those in the published literature, and appear to
      be similar to each other both demographically and in terms of the high average
      tablets consumption (49-65 tablets per day), the serious non-steroidal anti
      inflammatory drug (NSAID) adverse drug reactions identified, and the long
      duration of misuse. Many had a history of alcohol or other drug use and mental
      health disorder. CONCLUSIONS: This study has identified that controls on OTC
      codeine analgesics in both countries were not sufficient to limit non-medical use
      of these products. As a result, cases identified in these two countries escalated
      the number of self-administered tablets taken daily for misuse, resulting in
      codeine dependence and serious NSAID toxicity secondary to this dependence.

PMID- 22143851
TI  - Usage and equity of access to isotretinoin in New Zealand by deprivation and
      ethnicity.
AB  - AIMS: Oral isotretinoin, for severe acne, was until March 2009 fully funded in
      New Zealand only if the prescription was written by a vocationally registered
      dermatologist. This funding restriction was argued on the basis of complexity of
      management and an appreciable risk of teratogenicity if given during pregnancy or
      within a month of conception. However, this funding restriction had the potential
      to create inequitable access barriers. This study was an audit examining the use
      of isotretinoin by deprivation level and ethnicity, in order to examine potential
      inequities in use. METHOD: Dispensed prescription data for funded isotretinoin,
      for the year ending June 2008, held in a national repository was analysed using
      simple descriptive methods based on ethnicity and deprivation level. The same
      analysis was carried out for cyproterone acetate with ethinyloestradiol, another
      acne pharmaceutical available on prescription with no funding restrictions. There
      was demographic data on 60% of prescriptions based on the health identification
      number NHI. RESULTS: People living in more deprived areas (as defined by NZDep
      Index) were less likely to use isotretinoin, as were Maori and Pacific people.
      The association with deprivation level was not present for cyproterone acetate
      with ethinyloestradiol, although disparities in use by ethnicity remained.
      CONCLUSIONS: Given there is no evidence for lower rates of acne for Maori and
      Pacific people, the reasons may include financial and other barriers.

PMID- 22143852
TI  - Pharmacological management of children's asthma in general practice: findings
      from a community-based cross-sectional survey in Auckland, New Zealand.
AB  - AIM: To describe the pharmacological management of children's asthma and to
      assess whether there were ethnic differences in pharmacological management.
      METHODS: A community-based, cross-sectional, interviewer administered face-to
      face survey. The sample (n=583) included the caregivers of 221 Maori, 173
      Pacific, and 189 European/other children. Data collected included
      sociodemographic information, and medications received and medication delivery
      devices used in the 12 months prior to interview. Descriptive and logistic
      regression analyses to investigate ethnic differences in pharmacologic management
      were undertaken. RESULTS: Spacer devices were used by 80% of children under 7
      years of age and 34% of children 7 years or over. No ethnic differences in the
      use of these devices were observed. Maori (58%) and Pacific (65%) were
      significantly (p<0.0001) more likely to have been given a nebuliser
      (European/other 34%). Most (96%) children received inhaled beta-agonists and
      there were no ethnic differences for these medications. Overall, 69% of children
      had received inhaled corticosteroids (ICS) and there were no significant ethnic
      differences in receipt of these medications. However, only 68-78% of children in
      the moderate, severe, and very severe morbidity groups reported inhaled
      corticosteroids use in the previous 12 months, suggesting that this group is
      being under-treated. Morbidity stratified analyses suggested that Maori and
      Pacific children who had experienced severe morbidity in the previous 12 months
      were less likely to have received ICS. CONCLUSIONS: Some aspects of the
      pharmacological management of asthma are more consistent with recommendations in
      evidence-based guidelines than previously reported in NZ. The proportion of
      children with asthma who were receiving beta agonists and ICS were higher than
      that previously reported in NZ and the reported use of anticholinergics was low.
      However, other findings show there is still room for further improvements to be
      made, particularly with respect to the use of inhaled corticosteroids among
      children who experience significant morbidity, the use of nebulisers, and the use
      of spacer devices. The implementation of clinical quality assurance activities
      that support primary health organisations and providers to monitor and improve
      the delivery of evidence-based asthma care could further improve asthma outcomes.

PMID- 22143853
TI  - Median sternotomy scar assessment.
AB  - INTRODUCTION: Median sternotomy wounds are formed following most cardiac surgery.
      These wounds may heal with problematic scars. We hypothesise that midline
      sternotomy scars will scar poorly in general and in comparison with control
      scarring from other sites. METHODS: We evaluated 50 patients with mature median
      sternotomy scars using the Patient and Observer Scar Assessment Scale (POSAS),
      the Manchester Scar Scale (MSS) and photographs. Different scar features were
      assessed using these scales. RESULTS: Patients were on average 65.9 years old,
      predominantly male (72%) and Caucasian (94%). Overall, 11 patients (22%)
      expressed concern over a symptomatic or poor scar with seven patients (14%)
      complaining of pruritis and three patients (6%) disappointed with the cosmesis of
      the scar. The clinician found five patients (10%) to have poor scarring defined
      as hypertrophic scarring. The predominant scarring characteristics assessed by
      the clinician were colouration, variable relief and increased contour which are
      the main areas of concern. DISCUSSION: Our study shows that median sternotomy
      scarring can be problematic with 1 in 5 patients symptomatic and 1 in 10 patients
      developing hypertrophic scarring. Thus, this predominantly Caucasion population
      has a low but significant rate of scar problems in comparison to median
      sternotomy scarring in other populations. We could not identify patient factors
      which were predictive for poor scarring but anatomical location may be a key
      factor. Overall, we believe that median sternotomy patients should be offered
      preventative treatment to ensure the best scar outcome.

PMID- 22143854
TI  - Academic performance and career choices of older medical students at the
      University of Otago.
AB  - AIMS: To compare the academic performance and postgraduate career choices of a
      cohort of medical students who are older and more life experienced at time of
      medical school entry ("Other Category" students) with students admitted through
      standard entry admission pathways. METHODS: Examination performance, graduation
      rates, postgraduate specialisation and geographical location were compared
      between Other Category students and students entering via Standard Entry
      admission (including competitive first year entry and competitive graduate entry
      immediately after completing a Bachelor's degree). RESULTS: Compared with
      Standard Entry students, Other Category students had equivalent examination pass
      rates, significantly higher rates of distinction passes in examinations in Year 2
      (OR 1.86; 95% CI 1.05, 3.29; p=0.03) and Year 5 (OR 2.36; 95% CI 1.27, 4.37;
      p=0.005), and equivalent graduation rates. Retention of Other Category graduates
      in New Zealand was 14% higher than Standard Entry students over 10 years post
      graduation (p<0.0001), and a higher proportion had specialised in General
      Practice (p=0.04). CONCLUSIONS: Compared with Standard Entry students, Other
      Category medical students had higher rates of distinction grades in examination
      results, higher rates of retention in NZ post-graduation, and a higher proportion
      taking up general practice as a specialty. These findings may be relevant in
      planning for recruitment and training of the future medical workforce in New
      Zealand.

PMID- 22143855
TI  - Do pharmaceutical score cards give us the answers we seek?
AB  - Few countries can afford to fund all pharmaceuticals for all of their people all
      of the time, and the current international economic climate brings this into
      clearer focus. Various agencies have tried to solve the problem in different
      ways, varying from funding a restricted list that applies to the whole
      population, to funding most medicines but with a significant part charge, or as
      in the United States, funding for only selected groups and leaving others to fend
      for themselves other than in an emergency. For countries like New Zealand and
      Australia who have universal health coverage but restricted (and different) lists
      of funded pharmaceuticals, comparisons of those lists can occur, but are
      problematic.  Comparisons need to be interpreted with caution as systems and
      policies vary between countries.  That one country funds more new medicines than
      the other is one thing, but the more important questions are whether one country
      gets more health gains and more value for precious health dollars than the other.

PMID- 22143857
TI  - Difficulties in diagnosing soft-tissue sarcomas: a case of synovial sarcoma of
      the foot.

PMID- 22143856
TI  - Positive provider interventions for enhancing influenza vaccination uptake among
      Pacific peoples in New Zealand.
AB  - Despite having reported influenza vaccination rates similar to New Zealand
      Europeans, Pacific peoples have significantly higher rates of infection,
      hospitalisation and intensive care unit admission than any other group in New
      Zealand. Much of this may be due to the presence of comorbidities. However, it is
      in the interest of Pacific health to promote vaccination widely within this
      group. Little has been written about what prevents and encourages positive
      vaccination amongst Pacific peoples. This article reviews current themes about
      vaccination practices amongst ethnic minorities with a view to identifying
      positive vaccination strategies for Pacific peoples living in New Zealand.

PMID- 22143858
TI  - Urinary incontinence in a young girl due to ectopic ureter: the importance of
      history in a diagnostic challenge.
AB  - In girls who are otherwise well and whose history is that of continuous wetting
      day and night, despite successful toilet training, for a lifelong history, an
      extravesical infrasphincteric ectopic ureteral orifice should be strongly
      suspected and imaging should be vigorously pursued. Here, delayed diagnosis of
      vaginal ectopic ureter in a young girl with a lifelong history of urinary
      incontinence is presented. The importance of history and imaging procedures are
      also discussed.

PMID- 22143859
TI  - Primary oral tuberculosis.

PMID- 22143860
TI  - Medical image. Pulmonary popcorn.

PMID- 22143861
TI  - Screening for prostate cancer is not recommended.

PMID- 22143862
TI  - A regional non-melanoma skin cancer (NMSC) collection as part of the National
      Cancer Registry.

PMID- 22143863
TI  - Valuation of lives 'saved' via control of urban air pollution.

PMID- 22143864
TI  - Waikato DHB website and Thames Hospital: a response to Dr Ridley-Smith's letter.

PMID- 22143865
TI  - An operando Raman study of molecular structure and reactivity of molybdenum(VI)
      oxide supported on anatase for the oxidative dehydrogenation of ethane.
AB  - Supported molybdenum oxide catalysts on TiO(2) (anatase) with surface densities
      in the range of 1.8-17.0 Mo per nm(2) were studied at temperatures of 410-480 
      degrees C for unraveling the configuration and molecular structure of the
      deposited (MoO(x))(n) species and examining their behavior for the ethane
      oxidative dehydrogenation (ODH). In situ Raman and in situ FTIR spectra under
      oxidizing conditions combined with (18)O/(16)O isotope exchange studies provide
      the first sound evidence for mono-oxo configuration for the deposited (MoO(x))(n)
      species on anatase. Isolated O=Mo(-O-)(3) tetra-coordinated species in C(3v)-like
      symmetry prevail at all surface coverages with a low presence of associated
      (polymeric) species (probably penta-coordinated) evidenced at high coverages,
      below the approximate monolayer of 6 Mo per nm(2). A mechanistic scenario for
      (18)O/(16)O isotope exchange and next-nearest-neighbor vibrational isotope effect
      is proposed at the molecular level to account for the pertinent spectral
      observations. Catalytic measurements for ethane ODH with simultaneous monitoring
      of operando Raman spectra were performed. The selectivity to ethylene increases
      with increasing surface density up to the monolayer coverage, where primary steps
      of ethane activation follow selective reaction pathways leading to ~100% C(2)H(4)
      selectivity. The operando Raman spectra and a quantitative exploitation of the
      relative normalized Mo=O band intensities for surface densities of 1.8-5.9 Mo per
      nm(2) and various residence times show that the terminal Mo=O sites are involved
      in non-selective reaction turnovers. Reaction routes follow primarily non
      selective pathways at low coverage and selective pathways at high coverage.
      Trends in the initial rates of ethane consumption (apparent reactivity per Mo) as
      a function of Mo surface density are discussed on the basis of several factors.

PMID- 22143866
TI  - Polar body morphology is not predictive of its cell division origin.
AB  - PURPOSE: This study sought to determine whether morphology of simultaneously
      biopsied polar bodies is predictive of their cell division origin. METHODS:
      Levels of heterozygosity were measured using single nucleotide polymorphism (SNP)
      microarrays in sequentially biopsied polar bodies to establish the predictive
      value on samples with known cell division origins. The validated method of
      predicting cell division origin of polar bodies using heterozygosity rates was
      then applied to simultaneously biopsied polar bodies which had origin predictions
      made by morphological assessment. RESULTS: SNP microarray heterozygosity analysis
      was proven to be 94% predictive when tested against the known origin of
      sequentially biopsied polar bodies (n = 133). This methodology subsequently
      demonstrated that morphology was only 63% consistent when tested on
      simultaneously biopsied polar bodies (n = 455; P < 0.0001). Predictions of the
      origins of aneuploidy using morphology assignment were also significantly
      different than with heterozygosity assignment of polar body cell division origin
      (P = 0.0003). CONCLUSIONS: Studies of the origin of aneuploidy utilizing
      morphological assignment of polar body cell division origin without
      heterozygosity analysis may be inaccurate and should be interpreted with caution.

PMID- 22143867
TI  - What yeast and cardiomyocytes share: ultradian oscillatory redox mechanisms of
      cellular coherence and survival.
AB  - The coherent and robust, yet sensitively adaptable, nature of organisms is an
      astonishing phenomenon that involves massive parallel processing and concerted
      network performance at the molecular level. Unravelling the dynamic complexities
      of the living state underlines the essential operation of ultradian oscillations,
      rhythms and clocks for the establishment and maintenance of functional order
      simultaneously on fast and slower timescales. Non-invasive monitoring of
      respiration, mitochondrial inner membrane potentials, and redox states
      (especially those of NAD(P)H, flavin, and the monochlorobimane complex of
      glutathione), even after more than 50 years research, continue to provide both
      new insights and biomedical applications. Experiments with yeast and in cardiac
      cells reveal astonishing parallels and similarities in their dynamic biochemical
      organization.

PMID- 22143868
TI  - Environmental experience within and across testing days determines the strength
      of human visuomotor adaptation.
AB  - The use of vision allows us to guide and modify our movements by appropriately
      transforming external sensory information into proper motor commands. We
      investigated how people learned visuomotor transformations in different visual
      feedback environments. These environments presented perturbations of visual sense
      of movement direction. Across experiments and testing days, we altered the
      likelihood of visual perturbation occurrence and the distribution of sign and
      strength of visual perturbation angles. We then observed how transformation of
      sensed error into incremental adaptation depended on visual perturbation angle
      and on environmental experience. We found that environmental context affected
      adaptive responses within a day and across days. The across-day effect was
      profound enough that people exhibited very weak or very strong adaptive
      sensitivity to identical stimuli, dependent solely on prior days' experience. We
      conclude that trial-by-trial adaptation to visual feedback is not fixed, but
      dependent on environmental experiences on both short and long time scales.

PMID- 22143869
TI  - Generalization properties of a "saccadic-like" hand-reaching adaptation along a
      single degree of freedom.
AB  - Visuomotor-adaptation experiments devoted to the study of plasticity are also
      used to indirectly test hypotheses about how the brain encodes the spatio
      temporal characteristics of arm movement directed at a visual target. A current
      major theory, the vectorial coding hypothesis, postulates that arm movements are
      processed differentially for direction and amplitude. This approach, at first
      developed in an extrinsic Cartesian frame of references, has been also adopted in
      an intrinsic joint space. In the present paper, we report an experiment that
      corroborates this last point of view. Subjects performed pointing movements in a
      one degree of freedom condition, while systematic self-attributed endpoint errors
      were introduced. Through an observation of motor behavior in a battery of pre-
      and post-tests, we suggested that adaptation consisted in an increase in the
      motor gain in the adapted direction, with a perfect transfer to all starting
      points in the experimental reaching space. We explained the results by the
      absence of intersensory conflict and of correlative sensory adaptive component.
      As this paradigm was adapted from the saccadic adaptation paradigm, we eventually
      compared the two paradigms and highlighted that both induced mostly motor
      effects.

PMID- 22143870
TI  - Behavioural and electrophysiological effects of visual paired associate context
      manipulations during encoding and recognition in younger adults, older adults and
      older cognitively declined adults.
AB  - The current study examined the EEG of young, old and old declined adults
      performing a visual paired associate task. In order to examine the effects of
      encoding context and stimulus repetition, target pairs were presented on either
      detailed or white backgrounds and were repeatedly presented during both early and
      late phases of encoding. Results indicated an increase in P300 amplitude in the
      right parietal cortex from early to late stages of encoding in older declined
      adults, whereas both younger adults and older controls showed a reduction in P300
      amplitude in this same area from early to late phase encoding. In the right
      hemisphere, stimuli encoded with a white background had larger P300 amplitudes
      than stimuli presented with a detailed background; however, in the left
      hemisphere, in the later stages of encoding, stimuli presented with a detailed
      background had larger amplitudes than stimuli presented with a white background.
      Behaviourally, there was better memory for congruent stimuli reinstated with a
      detailed background, but this finding was for older controls only. During
      recognition, there was a general trend for congruent stimuli to elicit a larger
      amplitude response than incongruent stimuli, suggesting a distinct effect of
      context reinstatement on underlying patterns of physiological responding.
      However, behavioural data suggest that older declined adults showed no memory
      benefits associated with context reinstatement. When compared with older declined
      adults, younger adults had larger P100 amplitude responses to stimuli presented
      during recognition, and overall, younger adults had faster recognition reaction
      times than older control and older declined adults. Further analysis of
      repetition effects and context-based hemispheric asymmetry may prove informative
      in identifying declining memory performance in the elderly, potentially before it
      becomes manifested behaviourally.

PMID- 22143871
TI  - Gaze fixation improves the stability of expert juggling.
AB  - Novice and expert jugglers employ different visuomotor strategies: whereas
      novices look at the balls around their zeniths, experts tend to fixate their gaze
      at a central location within the pattern (so-called gaze-through). A gaze-through
      strategy may reflect visuomotor parsimony, i.e., the use of simpler visuomotor
      (oculomotor and/or attentional) strategies as afforded by superior tossing
      accuracy and error corrections. In addition, the more stable gaze during a gaze
      through strategy may result in more accurate movement planning by providing a
      stable base for gaze-centered neural coding of ball motion and movement plans or
      for shifts in attention. To determine whether a stable gaze might indeed have
      such beneficial effects on juggling, we examined juggling variability during 3
      ball cascade juggling with and without constrained gaze fixation (at various
      depths) in expert performers (n = 5). Novice jugglers were included (n = 5) for
      comparison, even though our predictions pertained specifically to expert
      juggling. We indeed observed that experts, but not novices, juggled significantly
      less variable when fixating, compared to unconstrained viewing. Thus, while
      visuomotor parsimony might still contribute to the emergence of a gaze-through
      strategy, this study highlights an additional role for improved movement
      planning. This role may be engendered by gaze-centered coding and/or attentional
      control mechanisms in the brain.

PMID- 22143872
TI  - Direct-current-dependent shift of theta-burst-induced plasticity in the human
      motor cortex.
AB  - Animal studies using polarising currents have shown that induction of synaptic
      long-term potentiation (LTP) and long-term depression (LTD) by bursts of
      patterned stimulation is affected by the membrane potential of the postsynaptic
      neurone. The aim of the present experiments was to test whether it is possible to
      observe similar phenomena in humans with the aim of improving present protocols
      of inducing synaptic plasticity for therapeutic purposes. We tested whether the
      LTP/LTD-like after effects of transcranial theta-burst stimulation (TBS) of human
      motor cortex, an analogue of patterned electrical stimulation in animals, were
      affected by simultaneous transcranial direct-current stimulation (tDCS), a non
      invasive method of polarising cortical neurones in humans. Nine healthy
      volunteers were investigated in a single-blind, balanced cross-over study;
      continuous TBS (cTBS) was used to introduce LTD-like after effects, whereas
      intermittent TBS (iTBS) produced LTP-like effects. Each pattern was coupled with
      concurrent application of tDCS (<200 s, anodal, cathodal, sham). Cathodal tDCS
      increased the response to iTBS and abolished the effects of cTBS. Anodal tDCS
      changed the effects of cTBS towards facilitation, but had no impact on iTBS.
      Cortical motor thresholds and intracortical inhibitory/facilitatory networks were
      not altered by any of the stimulation protocols. We conclude that the after
      effects of TBS can be modulated by concurrent tDCS. We hypothesise that tDCS
      changes the membrane potential of the apical dendrites of cortical pyramidal
      neurones and that this changes the response to patterned synaptic input evoked by
      TBS. The data show that it may be possible to enhance LTP-like plasticity after
      TBS in the human cortex.

PMID- 22143873
TI  - A self-fitting hearing aid: need and concept.
AB  - The need for reliable access to hearing health care services is growing globally,
      particularly in developing countries and in remotely located, underserved regions
      in many parts of the developed world. Individuals with hearing loss in these
      areas are at a significant disadvantage due to the scarcity of local hearing
      health care professionals and the high cost of hearing aids. Current approaches
      to making hearing rehabilitation services more readily available to underserved
      populations include teleaudiology and the provision of amplification devices
      outside of the traditional provider-client relationship. Both strategies require
      access to such resources as dedicated equipment and/or specially trained staff.
      Another possible strategy is a self-fitting hearing aid, a personal amplification
      device that is equipped with an onboard tone generator to enable user-controlled,
      automated, in situ audiometry; an onboard prescription to determine the initial
      hearing aid settings; and a trainable algorithm to enable user-controlled fine
      tuning. The device is thus assembled, fitted, and managed by the user without the
      need for audiological or computer support. This article details the self-fitting
      concept and its potential application in both developing and developed countries.
      Potential advantages and disadvantages of such a device are discussed, and
      considerations for further investigations into the concept are presented.
      Overall, the concept is considered technologically viable with the main
      challenges anticipated to be development of clear, simple user instructions and a
      delivery model that ensures reliable supplies of instant-fit ear tips and
      batteries.

PMID- 22143874
TI  - Audiologist-driven versus patient-driven fine tuning of hearing instruments.
AB  - Two methods of fine tuning the initial settings of hearing aids were compared: An
      audiologist-driven approach--using real ear measurements and a patient-driven
      fine-tuning approach--using feedback from real-life situations. The patient
      driven fine tuning was conducted by employing the Amplifit((r)) II system using
      audiovideo clips. The audiologist-driven fine tuning was based on the NAL-NL1
      prescription rule. Both settings were compared using the same hearing aids in two
      6-week trial periods following a randomized blinded cross-over design. After each
      trial period, the settings were evaluated by insertion-gain measurements.
      Performance was evaluated by speech tests in quiet, in noise, and in time
      reversed speech, presented at 0 degrees  and with spatially separated sound
      sources. Subjective results were evaluated using extensive questionnaires and
      audiovisual video clips. A total of 73 participants were included. On average,
      higher gain values were found for the audiologist-driven settings than for the
      patient-driven settings, especially at 1000 and 2000 Hz. Better objective
      performance was obtained for the audiologist-driven settings for speech
      perception in quiet and in time-reversed speech. This was supported by better
      scores on a number of subjective judgments and in the subjective ratings of video
      clips. The perception of loud sounds scored higher than when patient-driven, but
      the overall preference was in favor of the audiologist-driven settings for 67% of
      the participants.

PMID- 22143875
TI  - Antibody engineering reveals the important role of J segments in the production
      efficiency of llama single-domain antibodies in Saccharomyces cerevisiae.
AB  - Variable domains of llama heavy-chain antibodies (VHH) are becoming a potent tool
      for a wide range of biotechnological and medical applications. Because of
      structural features typical of their single-domain nature, they are relatively
      easy to produce in lower eukaryotes, but it is not uncommon that some molecules
      have poor secretion efficiency. We therefore set out to study the production
      yield of VHH. We computationally identified five key residues that are crucial
      for folding and secretion, and we validated their importance with systematic site
      directed mutations. The observation that all key residues were localised in the V
      segment, in proximity of the J segment of VHH, led us to study the importance of
      J segment in secretion efficiency. Intriguingly, we found that the use of
      specific J segments in VHH could strongly influence the production yield.
      Sequence analysis and expression experiments strongly suggested that interactions
      with chaperones, especially with the J segment, are a crucial aspect of the
      production yield of VHH.

PMID- 22143876
TI  - Evolving pattern of laparoscopic gastric band access port complications.
AB  - Laparoscopic gastric banding (LGB) is the commonest bariatric procedure in
      Australia. The commonest complication of LGB is access port or tubing (AP/T)
      problems, requiring revisional surgery. The aim of this study was to document the
      evolving pattern of AP/T complications. All patients whose LGB procedure
      (Allergan(TM) Bands) and AP/T revision (Allergan(TM) port revision sets) were
      performed by one surgeon (1999 to 2008) were included, giving 167 AP/T revisions
      in 124 patients out of a total 1,928 LGB patients. All patient follow-up details
      were prospectively recorded and retrospectively analysed. Incidence of LGB AP/T
      problems was 8.7%. Mean time to first AP/T revision was 2 years. Over the last 4
      years of the series, the number of LGB insertions was constant, but the number of
      AP/T revisions progressively increased. Twenty-seven percent of AP/T revision
      patients required two or more AP/T revisions. Sixty-two percent of the AP/T
      complications were leaks. Half the AP complications were flipping of the AP.
      There was no correlation of AP/T problems with any changes to port design to
      date. Infection rate for LGB insertion was 0.67%. The incidence of LGB AP/T
      complications progressively increases with duration after LGB insertion.
      Occurrence of one AP/T problem appears to select a subgroup more likely to
      experience further AP/T problems. To date, revisions of port design do not appear
      to have solved AP/T problems. Recent introduction of a significantly redesigned
      port may reduce AP/T failures.

PMID- 22143877
TI  - Electrochemical detection of high-sensitivity CRP inside a microfluidic device by
      numerical and experimental studies.
AB  - The concentration of C-reactive protein (CRP), a classic acute phase plasma
      protein, increases rapidly in response to tissue infection or inflammation,
      especially in cases of cardiovascular disease and stroke. Thus, highly sensitive
      monitoring of the CRP concentration plays a pivotal role in detecting these
      diseases. Many researchers have studied methods for the detection of CRP
      concentrations such as optical, mechanical, and electrochemical techniques inside
      microfluidic devices. While significant progress has been made towards improving
      the resolution and sensitivity of detection, only a few studies have
      systematically analyzed the CRP concentration using both numerical and
      experimental approaches. Specifically, systematic analyses of the electrochemical
      detection of high-sensitivity CRP (hsCRP) using an enzyme-linked immunosorbant
      assay (ELISA) inside a microfluidic device have never been conducted. In this
      paper, we systematically analyzed the electrochemical detection of CRP modified
      through the attachment of an alkaline phosphatase (ALP-labeled CRP) using ELISA
      inside a chip. For this analysis, we developed a model based on antigen-antibody
      binding kinetics theory for the numerical quantification of the CRP
      concentration. We also experimentally measured the current value corresponding to
      the ALP-labeled CRP concentration inside the microfluidic chip. The measured
      value closely matched the calculated value obtained by numerical simulation using
      the developed model. Through this comparison, we validated the numerical
      simulation methods, and the calculated and measured values. Lastly, we examined
      the effects of various microfluidic parameters on electrochemical detection of
      the ALP-labeled CRP concentration using numerical simulations. The results of
      these simulations provide insight into the microfluidic electrochemical reactions
      used for protein detection. Furthermore, the results described in this study
      should be useful for the design and optimization of electrochemical immunoassay
      chips for the detection of target proteins.

PMID- 22143878
TI  - Immunocapture of prostate cancer cells by use of anti-PSMA antibodies in
      microdevices.
AB  - Patients suffering from cancer can shed tumor cells into the bloodstream, leading
      to one of the most important mechanisms of metastasis. As such, the capture of
      these cells is of great interest. Circulating tumor cells are typically extracted
      from circulation through positive selection with the epithelial cell-adhesion
      molecule (EpCAM), leading to currently unknown biases when cells are undergoing
      epithelial-to-mesenchymal transition. For prostate cancer, prostate-specific
      membrane antigen (PSMA) presents a compelling target for immunocapture, as PSMA
      levels increase in higher-grade cancers and metastatic disease and are specific
      to the prostate epithelium. This study uses monoclonal antibodies J591 and J415
      antibodies that are highly specific for intact extracellular domains of PSMA on
      live cells-in microfluidic devices for the capture of LNCaPs, a PSMA-expressing
      immortalized prostate cancer cell line, over a range of concentrations and shear
      stresses relevant to immunocapture. Our results show that J591 outperforms J415
      and a mix of the two for prostate cancer capture, and that capture performance
      saturates following incubation with antibody concentrations of 10 micrograms per
      milliliter.

PMID- 22143879
TI  - NutriTRAILomics in prostate cancer: time to have two strings to one's bow.
AB  - The astonishing development of broad genomics and proteomics tools have catalyzed
      a new era in both therapeutic interventions and nutrition in prostate cancer. The
      terms pharmacogenomics and nutrigenomics have been derived out of their genetic
      forbears as large-scale genomics technologies have been established in the last
      decade. It is unquestionable that rationale of both disciplines is to
      individualize or personalize medicine and food and nutrition, and eventually
      health, by tailoring the drug or the food to the individual genotype. The purpose
      of this review is to significantly inspect results from current research
      concerning the mechanisms of action of phytonutrients and potential effects on
      prostate cancer. Substantial emerging data supports the synergistic
      adiministration of nutraceuticals with TRAIL in prostate cancer progression to
      circumvent TRAIL refractoriness. Nonetheless, developing novel scientific methods
      for discovery, validation, characterization and standardization of these
      multicomponent phyto-therapeutics is vital to their recognition into mainstream
      medicine. The key to interpret a personalized response is a greater comprehension
      of nutrigenomics, proteomics and metabolomics.

PMID- 22143880
TI  - ASYMMETRIC LEAVES2 gene, a member of LOB/AS2 family of Arabidopsis thaliana,
      causes an abaxializing leaves in transgenic cockscomb.
AB  - The leaf primordium derives from the peripheral zone of shoot apical meristem.
      During the formation of leaf primordia, they need to establish the proximodistal,
      mediolateral, and ab/adaxial axes. Among these axes, the ab/adaxial axis might be
      the most important. ASYMMETRIC LEAVES2 (AS2) gene is a member of AS2/LATERAL
      ORGAN BOUNDARY (LOB) family of Arabidopsis thaliana. In this work, we transformed
      35S:AS2 transgene constructs to cockscomb (Celosia cristata) via Agrobacterium
      tumefaciens. All primary transformants subsequently obtained were placed into
      phenotypic categories and self-pollinated. As a whole, a total of 44 T1 35S:AS2
      cockscomb plants obtained were grouped into two major categories: (I) slightly
      wrinkled leaves (28/44), (II) extremely curved leaves (16/44), on the basis of
      their leaf phenotypes. Furthermore, we characterized the anatomical features of
      these malformed leaves; and found the transformation of adaxial cell types into
      abaxial cell ones. A series of data suggest that AS2 might be involved in the
      determination of abaxial polarity in cockscomb plants. However, a few research
      teams have reported that AS2 might be involved in the determination of adaxial
      polarity in leaf primodia of Arabidopsis thaliana. These data above indicate that
      the roles of the same ab/adaxial determinant might differ between distinct
      species. At last, the different function of AS2 in distinct species was
      discussed.

PMID- 22143881
TI  - Plant traits and decomposition: are the relationships for roots comparable to
      those for leaves?
AB  - BACKGROUND AND AIMS: Fine root decomposition is an important determinant of
      nutrient and carbon cycling in grasslands; however, little is known about the
      factors controlling root decomposition among species. Our aim was to investigate
      whether interspecific variation in the potential decomposition rate of fine roots
      could be accounted for by root chemical and morphological traits, life history
      and taxonomic affiliation. We also investigated the co-ordinated variation in
      root and leaf traits and potential decomposition rates. METHODS: We analysed
      potential decomposition rates and the chemical and morphological traits of fine
      roots on 18 Mediterranean herbaceous species grown in controlled conditions. The
      results were compared with those obtained for leaves in a previous study
      conducted on similar species. KEY RESULTS: Differences in the potential
      decomposition rates of fine roots between species were accounted for by root
      chemical composition, but not by morphological traits. The root potential
      decomposition rate varied with taxonomy, but not with life history. Poaceae, with
      high cellulose concentration and low concentrations of soluble compounds and
      phosphorus, decomposed more slowly than Asteraceae and Fabaceae. Patterns of root
      traits, including decomposition rate, mirrored those of leaf traits, resulting in
      a similar species clustering. CONCLUSIONS: The highly co-ordinated variation of
      roots and leaves in terms of traits and potential decomposition rate suggests
      that changes in the functional composition of communities in response to
      anthropogenic changes will strongly affect biogeochemical cycles at the ecosystem
      level.

PMID- 22143882
TI  - High skin temperature and hypohydration impair aerobic performance.
AB  - This paper reviews the roles of hot skin (>35 degrees C) and body water deficits
      (>2% body mass; hypohydration) in impairing submaximal aerobic performance. Hot
      skin is associated with high skin blood flow requirements and hypohydration is
      associated with reduced cardiac filling, both of which act to reduce aerobic
      reserve. In euhydrated subjects, hot skin alone (with a modest core temperature
      elevation) impairs submaximal aerobic performance. Conversely, aerobic
      performance is sustained with core temperatures >40 degrees C if skin
      temperatures are cool-warm when euhydrated. No study has demonstrated that high
      core temperature (~40 degrees C) alone, without coexisting hot skin, will impair
      aerobic performance. In hypohydrated subjects, aerobic performance begins to be
      impaired when skin temperatures exceed 27 degrees C, and even warmer skin
      exacerbates the aerobic performance impairment (-1.5% for each 1 degrees C skin
      temperature). We conclude that hot skin (high skin blood flow requirements from
      narrow skin temperature to core temperature gradients), not high core
      temperature, is the 'primary' factor impairing aerobic exercise performance when
      euhydrated and that hypohydration exacerbates this effect.

PMID- 22143883
TI  - Functional assembly of mammalian cochlear hair cells.
AB  - Hair cells in the mammalian inner ear convert sound into electrical signals that
      are relayed to the nervous system by the chemical neurotransmitter glutamate.
      Electrical information encoding sound is then passed through the central nervous
      system to the higher auditory centres in the brain, where it is used to construct
      a temporally and spatially accurate representation of the auditory landscape. To
      achieve this, hair cells must encode fundamental properties of sound stimuli at
      extremely high rates, not only during mechano-electrical transduction, which
      occurs in the hair bundles at the cell apex, but also during electrochemical
      transduction at the specialized ribbon synapses at the cell base. How is the
      development of such a sophisticated cell regulated? More specifically, to what
      extent does physiological activity contribute to the progression of the intrinsic
      genetic programmes that drive cell differentiation? Hair cell differentiation
      takes about 3 weeks in most rodents, from terminal mitosis during embryonic
      development to the onset of hearing around 2 weeks after birth. Until recent
      years, most of the molecules involved in hair cell development and function were
      unknown, which was mainly due to difficulties in working with the mammalian
      cochlea and the very small number of hair cells, about 16,000 in humans, present
      in the auditory organ. Recent advances in the ability to record from the acutely
      isolated cochlea maintained in near-physiological conditions, combined with the
      use of genetically modified mouse models, has allowed the identification of
      several proteins and molecular mechanisms that are crucial for the maturation and
      function of hair cells. In this article, I highlight recent findings from my
      laboratory that have furthered our understanding of how developing hair cells
      acquire the remarkable sensitivity of adult auditory sensory receptors.

PMID- 22143884
TI  - Assessment of gastric emptying and duodenal motility upon ingestion of a liquid
      meal using rapid magnetic resonance imaging.
AB  - Gastric emptying is achieved by co-operation between gastric and duodenal motor
      activity. Therefore, evaluation of gastric emptying and its associated mechanisms
      would benefit clinical therapy as well as medical research. Healthy volunteers
      underwent rapid magnetic resonance imaging (MRI) of the abdomen along the coronal
      plane after ingestion of a liquid meal. The gastric fundal and duodenal areas
      were quantified semi-automatically by self-developed segment software. The
      average gastric fundal area determined by the serosal end in 40 sequential images
      was reduced to ~81% 30 min after and to ~70% 60 min after ingestion of a liquid
      meal. The average duodenal area also decreased to ~86% after 30 min and to 83%
      after 60 min. In contrast, changes in the centre of gravity increased to about
      fivefold after 30 min and to about threefold after 60 min. The mean velocity of
      the duodenal wall mimicked changes in the centre of gravity. The application of
      metoclopramide, a dopamine D(2) receptor antagonist, accelerated gastric
      emptying, presumably due to facilitated duodenal activity even immediately after
      liquid meal ingestion. The ingestion of water caused fast gastric emptying in 30
      min, accompanied by high duodenal motility, but it ceased after 60 min,
      presumably reflecting complete gastric emptying. A rapid MRI scan visualized the
      association between gastric emptying and duodenal motility that could be modified
      by calories and dopaminergic neurotransmission. Changes in the centre of gravity
      and mean velocity of the duodenal wall appear to quantify the motility obtained
      from cine MRI accurately.

PMID- 22143885
TI  - A genome-wide RNAi screen in mouse embryonic stem cells identifies Mp1 as a key
      mediator of differentiation.
AB  - Despite intense investigation of intrinsic and extrinsic factors that regulate
      pluripotency, the process of initial fate commitment of embryonic stem (ES) cells
      is still poorly understood. We used a genome-wide short hairpin RNA screen in
      mouse ES cells to identify genes that are essential for initiation of
      differentiation. Knockdown of the scaffolding protein Mek binding protein 1 (Mp1,
      also known as Lamtor3 or Map2k1ip1) stimulated self-renewal of ES cells, blocked
      differentiation, and promoted proliferation. Fibroblast growth factor 4 (FGF4)
      signaling is required for initial fate commitment of ES cells. Knockdown of Mp1
      inhibited FGF4-induced differentiation but did not alter FGF4-driven
      proliferation. This uncoupling of differentiation and proliferation was also
      observed when oncogenic Ras isoforms were overexpressed in ES cells. Knockdown of
      Mp1 redirected FGF4 signaling from differentiation toward pluripotency and up
      regulated the pluripotency-related genes Esrrb, Rex1, Tcl1, and Sox2. We also
      found that human germ cell tumors (GCTs) express low amounts of Mp1 in the
      invasive embryonic carcinoma and seminoma histologies and higher amounts of Mp1
      in the noninvasive carcinoma in situ precursor and differentiated components.
      Knockdown of Mp1 in invasive GCT cells resulted in resistance to differentiation,
      thereby showing a functional role for Mp1 both in normal differentiation of ES
      cells and in germ cell cancer.

PMID- 22143886
TI  - Langerhans cell antigen capture through tight junctions confers preemptive
      immunity in experimental staphylococcal scalded skin syndrome.
AB  - Epidermal Langerhans cells (LCs) extend dendrites through tight junctions (TJs)
      to survey the skin surface, but their immunological contribution in vivo remains
      elusive. We show that LCs were essential for inducing IgG(1) responses to patch
      immunized ovalbumin in mice that lacked skin dendritic cell subsets. The
      significance of LC-induced humoral responses was demonstrated in a mouse model of
      staphylococcal scalded skin syndrome (SSSS), a severe blistering disease in which
      the desmosomal protein Dsg1 (desmoglein1) is cleaved by Staphylococcus aureus
      derived exfoliative toxin (ET). Importantly, ET did not penetrate TJs, and patch
      immunization did not alter epidermal integrity. Nevertheless, neutralizing anti
      ET IgG(1) was induced after patch immunization and abolished upon LC depletion,
      indicating that antigen capture through TJs by LCs induced humoral immunity.
      Strikingly, the ET-patched mice were protected from developing SSSS after
      intraperitoneal ET challenge, whereas LC-depleted mice were susceptible to SSSS,
      demonstrating a vital role for LC-induced IgG(1) in systemic defense against
      circulating toxin in vivo. Therefore, LCs elicit humoral immunity to antigens
      that have not yet violated the epidermal barrier, providing preemptive immunity
      against potentially pathogenic skin microbes. Targeting this immunological
      process confers protection with minimal invasiveness and should have a marked
      impact on future strategies for development of percutaneous vaccines.

PMID- 22143887
TI  - TAK1 in brain endothelial cells mediates fever and lethargy.
AB  - Systemic inflammation affects the brain, resulting in fever, anorexia, lethargy,
      and activation of the hypothalamus-pituitary-adrenal axis. How peripheral
      inflammatory signals reach the brain is still a matter of debate. One possibility
      is that, in response to inflammatory stimuli, brain endothelial cells in
      proximity to the thermoregulatory centers produce cyclooxygenase 2 (COX-2) and
      release prostaglandin E2, causing fever and sickness behavior. We show that
      expression of the MAP kinase kinase kinase TAK1 in brain endothelial cells is
      needed for interleukin 1beta (IL-1beta)-induced COX-2 production. Exploiting the
      selective expression of the thyroxine transporter Slco1c1 in brain endothelial
      cells, we generated a mouse line allowing inducible deletion of Tak1 specifically
      in brain endothelium. Mice lacking the Tak1 gene in brain endothelial cells
      showed a blunted fever response and reduced lethargy upon intravenous injection
      of the endogenous pyrogen IL-1beta. In conclusion, we demonstrate that TAK1 in
      brain endothelial cells induces COX-2, most likely by activating p38 MAPK and c
      Jun, and is necessary for fever and sickness behavior.

PMID- 22143888
TI  - Immature B cells preferentially switch to IgE with increased direct SMU to
      Sepsilon recombination.
AB  - Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces
      initially expressed CMU (IgM) constant regions (C(H)) exons with downstream C(H)
      exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from
      CMU to Cgamma1 (IgG1) and Cepsilon (IgE), the latter of which contributes to the
      pathogenesis of atopic diseases. Although Cepsilon CSR can occur directly from
      CMU, most mature peripheral B cells undergo CSR to Cepsilon indirectly, namely
      from CMU to Cgamma1, and subsequently to Cepsilon. Physiological mechanisms that
      influence CSR to Cgamma1 versus Cepsilon are incompletely understood. In this
      study, we report a role for B cell developmental maturity in IgE CSR. Based in
      part on a novel flow cytometric IgE CSR assay, we show that immature B cells
      preferentially switch to IgE versus IgG1 through a mechanism involving increased
      direct CSR from CMU to Cepsilon. Our findings suggest that IgE dysregulation in
      certain immunodeficiencies may be related to impaired B cell maturation.

PMID- 22143889
TI  - CEACAM1 dampens antitumor immunity by down-regulating NKG2D ligand expression on
      tumor cells.
AB  - Although carcinoembryonic antigen (CEA)-related cell adhesion molecule 1
      (CEACAM1) has been viewed as a tumor suppressor, increasing clinical evidence
      shows that high levels of CEACAM1 expression on tumors correlates with poor
      prognosis and high risk of metastasis. Here, we examined the consequences of
      CEACAM1 expression on tumor cells. We show that tumor cell-associated CEACAM1
      causes intracellular retention of various NKG2D ligands in mouse and human tumor
      cells. CEACAM1-silenced tumor cells expressed more cell surface NKG2D ligands and
      exhibited greater sensitivity to natural killer cell-mediated cytolysis in vitro
      and rejection in vivo. Our studies reveal a novel mechanism through which CEACAM1
      bearing tumor cells may escape immune-surveillance.

PMID- 22143890
TI  - Value of the SOFA score as a predictive model for short-term survival in high
      risk liver transplant recipients with a pre-transplant labMELD score >= 30.
AB  - INTRODUCTION: The Sequential Organ Failure Assessment (SOFA) score has been
      applied for the prediction of survival in critically ill patients. We analysed
      the value of the SOFA score for the prediction of short-term survival after liver
      transplantation in high-risk liver transplant recipients with a labMELD score
      >=30. PATIENTS AND METHODS: We conducted a retrospective single-centre analysis
      including 88 consecutive liver transplants in adults between January 1, 2007 and
      December 31, 2010 with a pre-transplant labMELD score >=30. The SOFA score was
      assessed preoperatively, directly after transplantation and on post-operative
      days (PODs) 1-10. Combined and living-related liver transplants were excluded.
      Receiver operating characteristic (ROC) curve analysis with the Hosmer-Lemeshow
      test and application of the Brier score were used to calculate sensitivity,
      specificity, overall model correctness and calibration. Cutoff values were
      selected with the best Youden index. RESULTS: ROC curve analysis showed areas
      under the curve (AUROCs) >0.8 for the SOFA score on PODs 1-10 for the prediction
      of hospital mortality, 30-day mortality and 3-month mortality with Hosmer
      Lemeshow test results that confirmed good model calibration (p > 0.05). The Brier
      score demonstrated an accuracy of prediction (<0.25) of hospital mortality, 30
      day mortality and 3-month mortality for the SOFA scores on PODs 4-9 indicating
      superior accuracy on PODs 7 and 8 with cutoff values for the SOFA score between
      16.5 and 18.5. The pre-transplant SOFA score failed to reach AUROCs >0.7 (0.603
      0.663) for the prediction of short-term survival. CONCLUSIONS: Our results
      confirm the usefulness of the SOFA score in high-risk liver recipients during the
      early post-operative course, especially on PODs 7-8 for the prediction of
      hospital mortality, 30-day mortality and 3-month mortality and may be useful to
      predict futile early acute retransplantation.

PMID- 22143891
TI  - Readers' theatre: a communication tool for colorectal cancer screening.
AB  - Colorectal cancer (CRC) is the second leading cause of cancer mortality for
      Alaska Native people, yet it can be almost totally prevented through colonoscopy
      screenings. PURPOSE: A 25-minute Readers' Theatre script was developed with and
      for Alaska Native and American Indian Community Health Workers (CHWs) and the
      people in their communities to provide CRC screening information, model ways to
      talk about CRC screening, increase comfort with talking about CRC, and encourage
      healthy lifestyle choices. METHODS: Grounded in Indigenous methodologies, this
      paper describes the collaborative development, implementation, and evaluation of
      a CRC Readers' Theatre. RESULTS: 94% (161/172) of participants from 11 Readers'
      Theatre completed a written evaluation. 90% (145) of participants reported
      feeling more comfortable talking about CRC and 77% (124) described healthy
      changes they planned to make. Readers' Theatre was associated with increased
      knowledge, comfort talking about CRC, and served as a catalyst for positive
      intent to change behavior.

PMID- 22143892
TI  - Synthesis and characterization of organo-scandium and yttrium complexes
      stabilized by phosphinoamide ligands.
AB  - Addition of three equivalents of phosphinoamine, (ArNHP(i)Pr(2)) [Ar = 3,5
      dimethylphenyl] to M(CH(2)SiMe(3))(3)(THF)(2) [M = Sc, Y] precursors gives
      complexes of the form (ArNP(i)Pr(2))(3)M(THF) [M = Sc, Y]. In the case of
      scandium, addition of Sc(CH(2)SiMe(3))(3)(THF)(2) to (ArNP(i)Pr(2))(3)Sc(THF)
      affords (ArNP(i)Pr(2))(2)Sc(CH(2)SiMe(3))(THF), which has been isolated and
      structurally characterized. In contrast, addition of Y(CH(2)SiMe(3))(3)(THF)(2)
      to (ArNP(i)Pr(2))(3)Y(THF) generates a distribution of phosphinoamide-containing
      products consistent with the formulations (ArNP(i)Pr(2))(2)Y(CH(2)SiMe(3))(THF)
      and (ArNP(i)Pr(2))Y(CH(2)SiMe(3))(2)(THF), as ascertained using NMR spectroscopy.
      Attempts to react the alkyl-containing phosphinoamide complexes with small
      molecules such as H(2) led to disproportionation type processes.

PMID- 22143893
TI  - Darwinian docking.
AB  - The Darwinian model of evolution is an optimization strategy that can be adapted
      to docking. It differs from the common use of genetic algorithms, primarily in
      its acceptance of diverse solutions over finding "global" optima. A related
      problem is selecting compounds using multiple criteria. I discuss these ideas and
      present the outlines of a protocol for selecting "hits" and "leads" in drug
      discovery.

PMID- 22143894
TI  - Higher multiple births in Switzerland: neonatal outcome and evolution over the
      last 20 years.
AB  - QUESTION UNDER STUDY: The study has following objectives: 1) to determine the
      incidence of higher-order multiple births from 2005 to 2008 in Switzerland and
      its evolution over the last twenty years, and 2) to analyse the neonatal outcome
      and its change over the last two decades. METHODS: Data on higher-order multiple
      births were retrospectively obtained from Swiss obstetric and neonatal hospitals
      and compared with results from the first two national surveys. RESULTS: The
      incidence of higher-order multiple births was 35.3/100,000 live births for
      triplets, 0.7/100,000 for quadruplets and 0.3/100,000 for quintuplets. All
      newborns were premature with a median gestational age of 32 1/7 weeks for
      triplets, 29 2/7 weeks for quadruplets and 28 4/7 weeks for quintuplets. 94% of
      triplets and all quadruplets and quintuplets survived the neonatal period. Over
      the last two decades, the incidence of quadruplet and quintuplet births has
      fallen, while that of triplet births has risen by 40%. The perinatal mortality of
      triplets has decreased and the neonatal morbidity, mainly respiratory distress,
      has remained constant. CONCLUSION: Higher-order multiple births have a high
      morbidity that has not improved over the last two decades. The incidence of
      higher-order multiple births is still increasing, which demonstrates that
      reproductive medicine in Switzerland is not yet sufficiently controlled and
      monitored.

PMID- 22143895
TI  - Ectopic expression of SOX9 in osteoblasts alters bone mechanical properties.
AB  - Osteoporosis is a common skeletal disease characterized by low bone mass and
      microarchitectural deterioration of bone tissue, with a consequent increase in
      bone fragility and susceptibility to fracture. We previously demonstrated that
      Col1a1-SOX9 transgenic (TG) mice, in which SOX9 specifically expresses in
      osteoblasts driven by a 2.3-kb Col1a1 promoter, display osteopenia during the
      early postnatal stage. In this study, to further analyze the osteopenia phenotype
      and especially the effect of the osteoblast-specific expression of SOX9 on bone
      mechanical properties, we performed bone geometry and mechanical property
      analysis of long bones from Col1a1-SOX9 TG mice and wild-type littermates (WT) at
      different time points. Interestingly, after body weight adjustment, TG mice had
      similar whole-bone strength as WT mice but significantly thinner cortical bone,
      lower elastic modulus, and higher moment of inertia. Thus, osteoblast-specific
      SOX9 expression results in altered bone structure and material properties.
      Furthermore, the expression levels of Pcna, Col1a1, osteocalcin, and the
      Opg/Rankl ratio in TG mice were significantly lower until 4 months of age
      compared with WT mice, suggesting that TG mice have dysregulated bone
      homeostasis. Finally, bone marrow stromal cells (MSCs) isolated from TG mice
      display enhanced adipocyte differentiation and decreased osteoblast
      differentiation in vitro, suggesting that osteoblast-specific expression of SOX9
      can lead to altered mesenchymal stem cell differentiation potentials. In
      conclusion, our study implies that SOX9 activity has to be tightly regulated in
      the adult skeleton to ensure optimal bone quality.

PMID- 22143897
TI  - Abstracts of the UCD School of Medicine and Medical Science, Summer Student
      Research Awards. October 5, 2011. Dublin, Ireland.

PMID- 22143896
TI  - The expression and function of microRNAs in chondrogenesis and osteoarthritis.
AB  - OBJECTIVE: To use an in vitro model of chondrogenesis to identify microRNAs
      (miRNAs) with a functional role in cartilage homeostasis. METHODS: The expression
      of miRNAs was measured in the ATDC5 cell model of chondrogenesis using microarray
      and was verified using quantitative reverse transcription-polymerase chain
      reaction. MicroRNA expression was localized by in situ hybridization. Predicted
      miRNA target genes were validated using 3'-untranslated region-Luc reporter
      plasmids containing either wild-type sequences or mutants of the miRNA target
      sequence. Signaling through the Smad pathway was measured using a (CAGA)(12) -Luc
      reporter. RESULTS: The expression of several miRNAs was regulated during
      chondrogenesis. These included 39 miRNAs that are coexpressed with miRNA-140 (miR
      140), which is known to be involved in cartilage homeostasis and osteoarthritis
      (OA). Of these miRNAs, miR-455 resides within an intron of COL27A1 that encodes a
      cartilage collagen. When human OA cartilage was compared with cartilage obtained
      from patients with femoral neck fractures, the expression of both miR-140-5p and
      miR-455-3p was increased in OA cartilage. In situ hybridization showed miR-455-3p
      expression in the developing limbs of chicks and mice and in human OA cartilage.
      The expression of miR-455-3p was regulated by transforming growth factor beta
      (TGFbeta) ligands, and miRNA regulated TGFbeta signaling. ACVR2B, SMAD2, and
      CHRDL1 were direct targets of miR-455-3p and may mediate its functional impact on
      TGFbeta signaling. CONCLUSION: MicroRNA-455 is expressed during chondrogenesis
      and in adult articular cartilage, where it can regulate TGFbeta signaling,
      suppressing the Smad2/3 pathway. Diminished signaling through this pathway during
      the aging process and in OA chondrocytes is known to contribute to cartilage
      destruction. We propose that the increased expression of miR-455 in OA
      exacerbates this process and contributes to disease pathology.

PMID- 22143898
TI  - Induction of protective immunity against cryptococcosis.
AB  - Cryptococcus neoformans, the predominant etiological agent of cryptococcosis, is
      an encapsulated fungal pathogen that can cause life-threatening infections of the
      central nervous system in immune compromised individuals resulting in high
      morbidity and mortality. Consequently, several studies have endeavored to
      understand those mechanisms that mediate resistance and susceptibility to
      Cryptococcus infection. In this review, we will examine the contributions of
      various components of the innate and adaptive immune response toward protection
      against cryptococcosis. We will focus our discussion on studies presented at the
      8th International Conference on Cryptococcus and Cryptococcosis (ICCC).
      Remarkable progress has been made toward our understanding of host immunity and
      susceptibility to cryptococcal infection and the potential for vaccine
      development.

PMID- 22143899
TI  - Epidemiological findings and laboratory evaluation of sporotrichosis: a
      description of 103 cases in cats and dogs in southern Brazil.
AB  - Sporotrichosis is a subcutaneous mycosis, which affects mainly small animals, and
      is considered an important public health disease. This paper describes the
      epidemiological and laboratory characteristics of 103 clinical cases of
      sporotrichosis diagnosed over a 10-year period in southern Brazil. The 92 cats
      and 11 dogs from eight municipalities in Rio Grande do Sul State developed
      especially the disseminated cutaneous and fixed cutaneous forms of the disease.
      Respiratory signs such as sneezing, serous nasal discharge and dyspnea were found
      in about 57% of the animals. The detection of Sporothrix schenckii in different
      clinical samples showed highest isolation in testicles (46.6%), oral cavity
      (45.2%) and conjunctival mucosa (38.1%). A differentiated histological pattern
      was found between the fixed cutaneous and disseminated cutaneous (DC)
      manifestations of the disease; well-organized granulomas of nodular distribution
      and various fungal structures prevailed in the DC form in cats. Melanin detection
      in S. schenckii cells by the Fontana-Masson technique was positive in 45.4% of
      the samples. The study revealed that the State of Rio Grande do Sul is an endemic
      sporotrichosis area and demonstrated the possibility of involvement of other
      pathways in the infection and spread of the disease. In addition, it emphasized
      the importance of laboratory tests for mycosis confirmation, especially in dogs
      that develop clinical manifestations without the presence of cutaneous lesions.

PMID- 22143900
TI  - Co-combustion of solid recovered fuels in coal-fired power plants.
AB  - Currently, in ten coal-fired power plants in Germany solid recovered fuels from
      mixed municipal waste and production-specific commercial waste are co-combusted
      and experiments have been conducted at other locations. Overall, in 2010
      approximately 800,000 tonnes of these solid recovered fuels were used. In the
      coming years up to 2014 a slight decline in the quantity of materials used in co
      combustions is expected. The co-combustion activities are in part significantly
      influenced by increasing power supply from renewable sources of energy and their
      impact on the regime of coal-fired power plants usage. Moreover, price trends of
      CO2 allowances, solid recovered fuels as well as imported coal also have
      significant influence. In addition to the usage of solid recovered fuels with
      biogenic content, the co-combustion of pure renewable biofuels has become more
      important in coal-fired power plants. The power plant operators make high demands
      on the quality of solid recovered fuels. As the operational experience shows, a
      set of problems may be posed by co-combustion. The key factors in process
      engineering are firing technique and corrosion. A significant ecological key
      factor is the emission of pollutants into the atmosphere. The results of this
      study derive from research made on the basis of an extensive literature search as
      well as a survey on power plant operators in Germany. The data from operators was
      updated in spring 2011.

PMID- 22143901
TI  - Do action goals mediate social inhibition of return?
AB  - Social inhibition of return is the phenomenon whereby an individual is slower to
      reach to locations to which another individual has recently responded. Although
      this suggests that an observer represents another person's action, little is
      known about which aspects of the action are encoded. The present work describes a
      series of three experiments examining whether social inhibition of return
      represents the endpoint goal of the action, i.e., is 'goal based'. Pairs of
      participants sat opposite to one another and alternated responses to a cued or
      non-cued object presented on a table top. Importantly, either the two
      participants performed the same interaction with the object or a different
      interaction. Although all our experiments showed social inhibition of return, the
      size of the effect was not modulated according to whether each participant had
      the same or different goal. We conclude that although the mechanisms giving rise
      to social inhibition of return do encode some aspects of a response they do not
      code for terminal action goals.

PMID- 22143903
TI  - Monte Carlo simulation of the effect of focal spot size on contrast-detail
      detectability.
AB  - A contrast-detail experiment was simulated using Monte Carlo methods, to test the
      hypothesis that quantum limitations lead to an optimum minimum focal spot size
      below which no further improvement in image quality may be obtained. The
      simulation included a variable X-ray tube focal spot size, patient equivalent
      water phantom, X-ray couch, automatic exposure control, anti-scatter grid and
      indirect digital radiography detector. A number of simplifications were necessary
      in order to limit the calculation time to 8 days per image. Four images were
      produced for each focal spot size and these were scored by eight experienced
      observers. The contrast-detail curves were found to improve monotonically as
      focal spot size was reduced, with the best images produced by a point source.
      This contradicts the hypothesis of quantum limitation of focal spot size. We
      conclude that further work is required on the optimization of focal spot size. To
      assist with this, a new definition of system detective quantum efficiency is
      suggested, that includes the focal spot modulation transfer function, but does
      not include scattered radiation from the patient.

PMID- 22143902
TI  - Cognitive control of feature bindings: evidence from children with autistic
      spectrum disorder.
AB  - Understanding how the brain integrates features from different domains that are
      processed in distinct cortical regions calls for the examination of integration
      processes. Recent studies of feature-repetition effects demonstrated interactions
      across perceptual features and action-related features: repeating only some
      features of the perception-action episode hinders performance. These partial
      repetition costs point to the existence of temporary memory traces (event files).
      However, the principles and the constraints that govern the management of such
      traces are still unclear. Here, we investigated whether children with autistic
      spectrum disorder (ASD) differ from typically developing children in managing
      episodic memory traces. The results show that both groups integrate stimulus
      features along with action features, but children with ASD exhibit larger partial
      repetition costs, suggesting lesser control and flexibility in updating episodic
      memory traces. The findings are discussed in the light of evidence for a central
      role of the dopaminergic system in cognitive integration, ASD, and cognitive
      control.

PMID- 22143904
TI  - Multiple hepatic hydatid cysts.

PMID- 22143905
TI  - RGD peptide immobilized on TiO2 nanotubes for increased bone marrow stromal cells
      adhesion and osteogenic gene expression.
AB  - Recently, TiO(2) nanotube layers are widely used in orthopedics and dental
      applications because of their good promotion effect on bone cells. Furthermore,
      peptide sequences such as arginine-glycine-aspartic acid are used to modify Ti
      implant for binding to cell surface integrins through motif. In this study, a
      cellular adhesive peptide of arginine-glycine-aspartic acid-cysteine (RGDC) was
      immobilized onto anodized TiO(2) nanotubes on Ti to examine its in vitro
      responses on rat bone marrow stromal cells (BMSCs). Materials were characterized
      by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy
      techniques. High-resolution C1s scans suggested the presence of RGDC on the
      surface and SEM images confirmed the nanotubes were not destroyed after
      modification. BMSCs adhesion and osteogenic gene expression were detected in
      TiO(2) nanotube layers with and without RGDC modification by fluorescence
      microscopy, confocal laser scanning microscopy, SEM, and realtime polymerase
      chain reaction (Real-time PCR). Results showed that the TiO(2) nanotube layers
      immobilized with RGDC increased BMSCs adhesion compared to nonfunctionalized
      nanotubes after 4 h of cultivation. Furthermore, the osteogenic gene expression
      of BMSCs was dramatically enhanced on the TiO(2) nanotube layers immobilized with
      RGDC (10 mM) compared to the TiO(2) nanotube layers immobilized with RGDC (1 mM)
      and non-functionalized anodized Ti. Our results from in vitro study provided
      evidence that Ti anodized to possess nanotubes and then further functionalized
      with RGDC should be further studied for the design of better biomedical implant
      surfaces.

PMID- 22143906
TI  - Microstructure and mechanical properties of glass-infiltrated Al2O3/ZrO2
      nanocomposites.
AB  - This work was to investigate the effect of zirconia nanoparticles content on
      microstructure and mechanical properties of glass-infiltrated alumina/zirconia
      composites (AZGs). A series of slip-cast zirconia-toughened alumina (ZTA)
      compacts containing 10, 20, 30 wt% nano-zirconia, respectively, were partially
      sintered at 1,250 degrees C for 2 h, then infiltrated with lanthanum borosilicate
      glass of lower thermal expansion at 1,180 degrees C for 4 h. A porosity ranging
      from 21 to 25% mainly with submicron pore size was demonstrated in the partially
      sintered ZTAs. Homogeneous distribution and micro-crystallization of
      intergranular glass phase was showed in the AZGs. The mechanical strength and
      fracture toughness of AZGs increased with zirconia content, the maximum (633.5 +/
      41.7, 6.7 +/- 0.6 MPa m(0.5)) were obtained in 30 wt% zirconia group, which were
      significantly higher than those in 10 wt% zirconia group (P < 0.05). The improved
      mechanical performance of AZGs containing 30 wt% zirconia was attributed to their
      larger zirconia content as well as thinner intergranular glass film.

PMID- 22143907
TI  - Electrospun fibrous scaffold of hydroxyapatite/poly (epsilon-caprolactone) for
      bone regeneration.
AB  - Development of fibrous scaffold of hydroxyapatite/biopolymer nanocomposite offers
      great potential in the field of bone regeneration and tissue engineering.
      Hydroxyapatite (HA)/poly (epsilon-caprolactone) (PCL) fibrous scaffolds were
      successfully prepared by electrospinning dopes containing HA and PCL in this
      work. It was found that pre-treating HA with gamma-glycioxypropyltrimethoxysilane
      (A-187) was effective in improving HA dispersion both in solutions and in a PCL
      matrix. Mechanical properties of the scaffolds were greatly enhanced by the
      filling of A187-HA. The bioactivity of PCL was remarkably improved by the
      addition of HA and A187-HA. Fibroblasts and osteoblasts were seeded on scaffolds
      to evaluate the effect of A-187 on biocompatibility of HA/PCL composites. Based
      on this study, good dispersion of HA in PCL matrix was granted by pretreatment of
      HA with A-187 and A187-HA/PCL fibrous scaffolds were obtained by electrospinning.
      These results demonstrated that the scaffolds may possess improved mechanical
      performance and good bioactivity due to A187-HA incorporation.

PMID- 22143908
TI  - Thermoresponsive hyperbranched copolymer with multi acrylate functionality for in
      situ cross-linkable hyaluronic acid composite semi-IPN hydrogel.
AB  - Thermoresponsive polymers have been widely used for in situ formed hydrogels in
      drug delivery and tissue engineering as they are easy to handle and their shape
      can easily conform to tissue defects. However, non-covalent bonding and
      mechanical weakness of these hydrogels limit their applications. In this study, a
      physically and chemically in situ cross-linkable hydrogel system was developed
      from a novel thermoresponsive hyperbranched PEG based copolymer with multi
      acrylate functionality, which was synthesized via an 'one pot and one step' in
      situ deactivation enhanced atom transfer radical co-polymerization of
      poly(ethylene glycol) diacrylate (PEGDA, M(n) = 258 g mol(-1)), poly(ethylene
      glycol) methyl ether methacrylate (PEGMEMA, M(n )= 475 g mol(-1)) and (2
      methoxyethoxy) ethyl methacrylate (MEO(2)MA). This hyperbranched copolymer was
      tailored to have the lower critical solution temperature to form physical
      gelation around 37 degrees C. Meanwhile, with high level of acrylate
      functionalities, a chemically cross-linked gel was formed from this copolymer
      using thiol functional cross-linker of pentaerythritol tetrakis (3
      mercaptopropionate) (QT) via thiol-ene Michael addition reaction. Furthermore, a
      semi-interpenetrated polymer networks (semi-IPN) structure was developed by
      combining this polymer with hyaluronic acid (HA), leading to an in situ cross
      linkable hydrogel with significantly increased porosity, enhanced swelling
      behavior and improved cell adhesion and viability both in 2D and 3D cell culture
      models.

PMID- 22143909
TI  - Novel biodegradable, biomimetic and functionalised polymer scaffolds to prevent
      expansion of post-infarct left ventricular remodelling.
AB  - Over the past decade, a large number of strategies and technologies have been
      developed to reduce heart failure progression. Among these, cardiac tissue
      engineering is one of the most promising. Aim of this study is to develop a 3D
      scaffold to treat cardiac failure. A new three-block copolymer, obtained from
      delta-valerolactone and polyoxyethylene, was synthesised under high vacuum
      without catalyst. Copolymer/gelatine blends were microfabricated to obtain a ECM
      like geometry. Structures were studied under morphological, mechanical,
      degradation and biological aspects. To prevent left ventricular remodelling,
      constructs were biofunctionalises with molecularly imprinted nanoparticles
      towards the matrix metalloproteinase MMP-9. Results showed that materials are
      able to reproduce the ECM structure with high resolution, mechanical properties
      were in the order of MPa similar to those of the native myocardium and cell
      viability was verified. Nanoparticles showed the capability to rebind MMP-9
      (specific rebinding 18.67) and to be permanently immobilised on the scaffold
      surface.

PMID- 22143910
TI  - Improvement in adhesion of the brackets to the tooth by sandblasting treatment.
AB  - In oral orthodontic treatments, achievement of a good adhesion between brackets
      and teeth surfaces is essential. One way to increase adhesion is to apply a
      surface treatment of teeth facing surfaces through the projection of abrasive
      particles to produce a surface roughness which improves adhesion of the bracket
      to the tooth, because of the significantly increased contact between the two
      surfaces. The effect on adhesion through the use of this technique in different
      types of brackets, as well as through the use of different blasting particles,
      however, is yet not well described. In this study we have included three types of
      brackets which are commonly used in orthodontic therapies (two of them a mesh
      type and the third one a micro-milled type) with a contact surface area of 11.16,
      8.85 and 6.89 mm(2) respectively. These brackets were used combined with a
      sandblasting treatment with two different types of abrasive particles, alumina
      (Al(2)O(3)) and silicon carbide (SiC) and applied to natural teeth in vitro. The
      abrasive particles used are bio-compatible and usually used in achieving
      increased roughness for improved adherence in biomedical materials. Sandblasting
      was performed at 2 bars for 2 s; three particle sizes were used: 80, 200 and 600
      MUm. Non-blasted samples were used as control. Each of the pieces were cemented
      to natural teeth with a self-curing composite. Samples were stored in physiologic
      serum at 5 degrees C temperature. Tensile tests were performed with a universal
      testing machine. Brackets treated with sandblasted particles were measured to
      have an increased adhesion as compared to the control sample. The highest bond
      strength was measured for samples sandblasted with alumina particles of 80 and
      200 MUm combined with micro-milled brackets. The recorded stresses did not exceed
      the tensile strength of tooth enamel.

PMID- 22143911
TI  - Repeat-dose sirolimus pharmacokinetics and pharmacodynamics in patients with
      hepatic allografts.
AB  - PURPOSE: To determine sirolimus steady-state pharmacokinetics, and to assess the
      relationship between time-normalized trough sirolimus concentration (C(min,TN))
      and evidence of efficacy (rejection and death) and adverse reactions (stomatitis
      and pneumonia) in liver allograft patients. METHODS: Dense sampling of sirolimus
      was performed over a single daily-dosing interval in 11 hepatic allograft
      recipients on day 28 and at 3 months after start of treatment. Serial trough
      concentration sampling was performed in 380 hepatic allograft recipients on days
      1, 7, 14, 28, 42, 60, 90, 180, 270 and 360 after start of treatment. Occurrence
      of stomatitis, pneumonia, rejection, and death were collected for 360 days after
      start of treatment. Noncompartmental pharmacokinetic parameters were analyzed in
      the 11 densely sampled patients; C(min,TN) was determined in the 380 patients.
      RESULTS: Mean maximum concentration (C(max)), time to C(max) (t(max)), area under
      the curve for the given dose interval (AUC(tau)), and whole blood oral clearance
      at 3 months were 20.8 +/- 7.6 ng/mL, 3 +/- 1 h, 338 +/- 144 ng.h/mL, and 10.0 +/-
      5.6 L/hr, respectively. In the 11 densely sampled patients, linear regression
      showed that C(min,TN) was highly predictive of AUC(tau) (r2 = 0.77, P < 0.0001)
      at each analysis time point. Logistic regression showed a relationship between
      C(min,TN) in the 380 patients and pneumonia occurrence, but not between C(min,TN)
      and stomatitis, rejection, or death. CONCLUSIONS: In this study, the
      pharmacokinetic profile of sirolimus in hepatic allograft patients was consistent
      with that of renal transplantation recipients. With the exception of pneumonia,
      no correlation was observed between C(min,TN) and the occurrence of adverse
      events of interest.

PMID- 22143912
TI  - Implementation of an automated signal detection method in the French
      pharmacovigilance database: a feasibility study.
AB  - PURPOSE: In France, early detection of adverse effects does not currently involve
      any automatic signal detection method. The present objective was to assess the
      feasibility and measure the potential benefit of the incorporation of an
      automatic signal detection tool (GPS(pH0)) in the French pharmacovigilance
      system. METHODS: GPS(pH0) was first applied to the data collected from 1 January
      2000 to 31 December 2008 and then to the data collected from 1 January 2000 to 31
      March 2009. A total of 1,414 original signals were detected. They were shared out
      for further expertise among 32 centres, i.e. the 31 Regional Pharmacovigilance
      Centres and the French medicine agency (AFSSAPS) pharmacovigilance department.
      RESULTS: The participating centres (n = 28) analysed 1,292 signals in May 2009.
      Overall, 277 signals whether known or unknown were thus considered worth
      following up. Half of the other 893 categorised signals were "well-known" (35.7%)
      and non-interpretable/non-pertinent signals (36.6%); 4% were not categorised
      because of a lack of time. Analysis of the signals was time-consuming, but the
      working time estimated by the participants was highly variable (median time: 6 h;
      minimum: 2 h maximum: 26 h). CONCLUSIONS: The results of this study are in favour
      of the integration of an automated signal detection tool to complement the
      current pharmacovigilance activities. The Anatomic Therapeutic Chemical for drug
      classification poses difficulties in many situations; the international
      proprietary name might be more efficient. The variability observed in the time
      needed for analysis suggests that a standardised methodology should be employed.
      Overall, the findings of this prospective study will contribute to refining the
      signal management procedure to be implemented in the future.

PMID- 22143913
TI  - MRI identifies plantar plate pathology in the forefoot of patients with
      rheumatoid arthritis.
AB  - Previous cadaveric studies have suggested that forefoot deformities at the
      metatarsophalangeal (MTP) joints in patients with rheumatoid arthritis (RA) might
      result from the failure of the ligamentous system and displacement of the plantar
      plates. This study aimed to examine the relationship between plantar plate
      pathology and the rheumatoid arthritis magnetic resonance imaging score (RAMRIS)
      of the lesser (second to fifth) MTP joints in patients with RA using high
      resolution 3 T magnetic resonance imaging (MRI). In 24 patients with RA, the
      forefoot was imaged using 3 T MRI. Proton density fat-suppressed, T2-weighted fat
      suppressed and T1-weighted post gadolinium sequences were acquired through 96
      lesser MTP joints. Images were scored for synovitis, bone marrow oedema and bone
      erosion using the RAMRIS system and the plantar plates were assessed for
      pathology. Seventeen females and 7 males with a mean age of 55.5 years (range 37
      71) and disease duration of 10.6 years (range 0.6-36) took part in the study.
      Plantar plate pathology was most frequently demonstrated on MRI at the fifth MTP
      joint. An association was demonstrated between plantar plate pathology and RAMRIS
      reported synovitis, bone marrow oedema and bone erosion at the fourth and fifth
      MTP joints. In patients with RA, 3 T MRI demonstrates that plantar plate
      pathology at the lesser MTP joints is associated with features of disease
      severity. Plantar plate pathology is more common at the fourth and fifth MTP
      joints in subjects with RA in contrast to the predilection for the second MTP
      reported previously in subjects without RA.

PMID- 22143914
TI  - Time-dependent inflammatory factor production and NFkappaB activation in a rodent
      model of intermittent hypoxia.
AB  - OBJECTIVE: To study the systemic production of inflammatory factors and
      activation of transcription factor nuclear factor kappa B (NF-kappaB) in response
      to different levels of intermittent hypoxia and time. METHODS: A total of 160
      male Wistar rats were divided randomly into five groups. The first three groups
      were exposed to 5%, 7.5% and 10% intermittent hypoxia (referred to as IH-1, IH-2,
      and IH-3 respectively), the fourth group were subjected to 10% sustained hypoxia
      (abbreviated as SH), and the control group were exposed to normal oxygen
      (designated SC). At the second, fourth, sixth, and eighth week, eight rats in
      each group were sacrificed to collect serum. Enzyme-linked immunosorbent assay
      (ELISA) was used to detect the serum concentration of tumour necrosis factor
      alpha (TNF-alpha), interleukin-8 (IL-8), interleukin-6 (IL-6) and interleukin-10
      (IL-10). Western blot was used to detect the protein levels of the phosphorylated
      NF-kappaB P65 in the nucleus of arterial endothelial cells. RESULTS: In all three
      IH groups serum levels of TNF-alpha, IL-8 and IL-6 showed consecutive increment
      from onset to the 6th week under intermittent hypoxia; the levels of TNF-alpha
      and IL-8 dropped slightly on the 8th week, whereas those of IL-6 continued to
      increase. The levels of IL-10 decreased and reached nadir at the 6th week of
      intermittent hypoxia treatment. The inflammatory response was the most pronounced
      in the 6th week, at which time the TNF-alpha, IL-8 and IL-6 levels in IH groups
      were significantly higher than in the SC and SH group (F = 30.04, 11.77, 18.589;
      p <0.05). IL-10 levels were significantly lower than the SC and SH group (F =
      10.403, p <0.05). Levels of TNF-alpha and IL-8 in the IH-1 group were
      significantly higher than those in the IH-3 group (F = 1.20, 34.68; p = 0.049,
      0.046). Protein levels of phosphorylated NF-kappaB P65 in endothelial cells
      collected from thoracic aorta in all three IH groups were significantly higher
      than those in SC and SH groups (F = 63.136, p = 0.01). A close correlation was
      identified between NF-kappaB p65 phosphorylation and the levels of TNF-alpha, IL
      8, IL-6 and IL-10 (p = 0.01). CONCLUSIONS: The inflammatory response, manifested
      by serum levels of inflammatory factors and nuclear accumulation of activated NF
      kappaB P65, was more serious in the IH group than in the SH and control group,
      and was dependent on hypoxia levels. This reaction increased initially and then
      decreased, which indicates the presence of compensatory mechanisms and an
      adaptive response to such stressors in the body. Notably, the correlation of
      NFkappaB activation to production of inflammatory factors under intermittent
      hypoxia implies an important role of this transcription factor in inflammation
      induced cardiovascular damage occurring during obstructive sleep apnoea (OSA),
      which has a typical breathing pattern of intermittent hypoxia.

PMID- 22143915
TI  - Storage globulins pass through the Golgi apparatus and multivesicular bodies in
      the absence of dense vesicle formation during early stages of cotyledon
      development in mung bean.
AB  - During seed development and maturation, large amounts of storage proteins are
      synthesized and deposited in protein storage vacuoles (PSVs). Multiple mechanisms
      have been proposed to be responsible for transporting storage proteins to PSVs in
      developing seeds. In this study, a specific antibody was raised against the mung
      bean (Vigna radiata) seed storage protein 8S globulin and its deposition was
      followed via immunogold electron microscopy in developing mung bean cotyledons.
      It is demonstrated that non-aggregated 8S globulins are present in multivesicular
      bodies (MVBs) in early stages of cotyledon development where neither dense
      vesicles (DVs) nor a PSV were recognizable. However, at later stages of cotyledon
      development, condensed globulins were visible in both DVs and distinct MVBs with
      a novel form of partitioning, with the internal vesicles being pushed to one
      sector of this organelle. These distinct MVBs were no longer sensitive to
      wortmannin. This study thus indicates a possible role for MVBs in transporting
      storage proteins to PSVs during the early stage of seed development prior to the
      involvement of DVs. In addition, wortmannin treatment is shown to induce DVs to
      form aggregates and to fuse with the plasma membrane.

PMID- 22143916
TI  - Light-regulated and cell-specific methylation of the maize PEPC promoter.
AB  - The molecular mechanisms governing PEPC expression in maize remain to be fully
      defined. Differential methylation of a region in the PEPC promoter has been shown
      to correlate with transcript accumulation, however, to date, investigations into
      the role of DNA methylation in maize PEPC expression have relied on the use of
      methylation-sensitive restriction enzymes. Bisulphite sequencing was used here to
      provide a single-base resolution methylation map of the maize PEPC promoter. It
      is shown that four cytosine residues in the PEPC promoter are heavily methylated
      in maize root tissue. In leaves, de-methylation of these cytosines is dependent
      on illumination and is coincident with elevated PEPC expression. Furthermore,
      light-regulated de-methylation of these cytosines occurs only in mesophyll cells.
      No methylation was discovered in the 0.6 kb promoter required for mesophyll
      specific expression indicating that cytosine methylation is not required to
      direct the cell-specificity of PEPC expression. This raises interesting questions
      regarding the function of the cell-specific cytosine de-methylation observed in
      the upstream region of the PEPC promoter.

PMID- 22143917
TI  - Light-harvesting chlorophyll a/b-binding proteins are required for stomatal
      response to abscisic acid in Arabidopsis.
AB  - The light-harvesting chlorophyll a/b binding proteins (LHCB) are perhaps the most
      abundant membrane proteins in nature. It is reported here that the down
      regulation or disruption of any member of the LHCB family, LHCB1, LHCB2, LHCB3,
      LHCB4, LHCB5, or LHCB6, reduces responsiveness of stomatal movement to ABA, and
      therefore results in a decrease in plant tolerance to drought stress in
      Arabidopsis thaliana. By contrast, over-expression of a LHCB member, LHCB6,
      enhances stomatal sensitivity to ABA. In addition, the reactive oxygen species
      (ROS) homeostasis and a set of ABA-responsive genes are altered in the lhcb
      mutants. These data demonstrate that LHCBs play a positive role in guard cell
      signalling in response to ABA and suggest that they may be involved in ABA
      signalling partly by modulating ROS homeostasis.

PMID- 22143918
TI  - Uncoupling of genomic and epigenetic signals in the maintenance and inheritance
      of heterochromatin domains in fission yeast.
AB  - Many essential aspects of genome function, including gene expression and
      chromosome segregation, are mediated throughout development and differentiation
      by changes in the chromatin state. Along with genomic signals encoded in the DNA,
      epigenetic processes regulate heritable gene expression patterns. Genomic signals
      such as enhancers, silencers, and repetitive DNA, while required for the
      establishment of alternative chromatin states, have an unclear role in epigenetic
      processes that underlie the persistence of chromatin states throughout
      development. Here, we demonstrate in fission yeast that the maintenance and
      inheritance of ectopic heterochromatin domains are independent of the genomic
      sequences necessary for their de novo establishment. We find that both structural
      heterochromatin and gene silencing can be stably maintained over an ~10-kb domain
      for up to hundreds of cell divisions in the absence of genomic sequences required
      for heterochromatin establishment, demonstrating the long-term persistence and
      stability of this chromatin state. The de novo heterochromatin, despite the
      absence of nucleation sequences, is also stably inherited through meiosis.
      Together, these studies provide evidence for chromatin-dependent, epigenetic
      control of gene silencing that is heritable, stable, and self-sustaining, even in
      the absence of the originating genomic signals.

PMID- 22143920
TI  - Multiple routes to subfunctionalization and gene duplicate specialization.
AB  - Gene duplication is arguably the most significant source of new functional
      genetic material. A better understanding of the processes that lead to the stable
      incorporation of gene duplications into the genome is important both because it
      relates to interspecific differences in genome composition and because it can
      shed light on why some classes of gene are more prone to duplication than others.
      Typically, models of gene duplication consider the periods before duplication,
      during the spread and fixation of a new duplicate, and following duplication as
      distinct phases without a common underlying selective environment. I consider a
      scenario where a gene that is initially expressed in multiple contexts can
      undergo mutations that alter its expression profile or its functional coding
      sequence. The selective regime that acts on the functional output of the allele
      copies carried by an individual is constant. If there is a potential selective
      benefit to having different coding sequences expressed in each context, then,
      regardless of the constraints on functional variation at the single-locus gene,
      the waiting time until a gene duplication is incorporated goes down as population
      size increases.

PMID- 22143919
TI  - Scrambling eggs: meiotic drive and the evolution of female recombination rates.
AB  - Theories to explain the prevalence of sex and recombination have long been a
      central theme of evolutionary biology. Yet despite decades of attention dedicated
      to the evolution of sex and recombination, the widespread pattern of sex
      differences in the recombination rate is not well understood and has received
      relatively little theoretical attention. Here, we argue that female meiotic
      drivers--alleles that increase in frequency by exploiting the asymmetric cell
      division of oogenesis--present a potent selective pressure favoring the
      modification of the female recombination rate. Because recombination plays a
      central role in shaping patterns of variation within and among dyads, modifiers
      of the female recombination rate can function as potent suppressors or enhancers
      of female meiotic drive. We show that when female recombination modifiers are
      unlinked to female drivers, recombination modifiers that suppress harmful female
      drive can spread. By contrast, a recombination modifier tightly linked to a
      driver can increase in frequency by enhancing female drive. Our results predict
      that rapidly evolving female recombination rates, particularly around
      centromeres, should be a common outcome of meiotic drive. We discuss how
      selection to modify the efficacy of meiotic drive may contribute to commonly
      observed patterns of sex differences in recombination.

PMID- 22143921
TI  - Quantitative trait Loci association mapping by imputation of strain origins in
      multifounder crosses.
AB  - Although mapping quantitative traits in inbred strains is simpler than mapping
      the analogous traits in humans, classical inbred crosses suffer from reduced
      genetic diversity compared to experimental designs involving outbred animal
      populations. Multiple crosses, for example the Complex Trait Consortium's eight
      way cross, circumvent these difficulties. However, complex mating schemes and
      systematic inbreeding raise substantial computational difficulties. Here we
      present a method for locally imputing the strain origins of each genotyped animal
      along its genome. Imputed origins then serve as mean effects in a multivariate
      Gaussian model for testing association between trait levels and local genomic
      variation. Imputation is a combinatorial process that assigns the maternal and
      paternal strain origin of each animal on the basis of observed genotypes and
      prior pedigree information. Without smoothing, imputation is likely to be ill
      defined or jump erratically from one strain to another as an animal's genome is
      traversed. In practice, one expects to see long stretches where strain origins
      are invariant. Smoothing can be achieved by penalizing strain changes from one
      marker to the next. A dynamic programming algorithm then solves the strain
      imputation process in one quick pass through the genome of an animal. Imputation
      accuracy exceeds 99% in practical examples and leads to high-resolution mapping
      in simulated and real data. The previous fastest quantitative trait loci (QTL)
      mapping software for dense genome scans reduced compute times to hours. Our
      implementation further reduces compute times from hours to minutes with no loss
      in statistical power. Indeed, power is enhanced for full pedigree data.

PMID- 22143922
TI  - Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial
      activation and joint destruction during mouse and human osteoarthritis.
AB  - OBJECTIVE: To investigate whether alarmins S100A8 and S100A9 are involved in
      mediating cartilage destruction during murine and human osteoarthritis (OA).
      METHODS: Two different murine models of OA that differed in terms of synovial
      activation were compared. Cartilage destruction was measured histologically.
      Synovial biopsy and serum samples from OA patients were derived from the Cohort
      Hip and Cohort Knee (CHECK) patients with symptomatic early OA. Expression of
      mediators in the synovium was measured by reverse transcription-polymerase chain
      reaction analysis and immunolocalization. RESULTS: In collagenase-induced OA,
      which showed marked synovial activation, interleukin-1beta was expressed at
      significant levels only during the early stages of disease, whereas S100A8 and
      S100A9 expression remained high for a prolonged period of time (up to day 21
      after induction). In S100A9-knockout mice, we found a major impact of S100A8 and
      S100A9 on synovial activation (62% inhibition) and OA cartilage destruction (45
      73% inhibition) as compared to wild-type controls. In contrast, in the surgically
      induced destabilized medial meniscus model, in which synovial involvement is
      scant, we found no role of S100A8 and S100A9 in the focal OA cartilage
      destruction. Examination of arthroscopic synovial biopsy samples from patients in
      the early symptomatic OA CHECK cohort revealed substantial levels of S100A8 and
      S100A9 messenger RNA and protein, which correlated significantly with synovial
      lining thickness, cellularity in the subintima, and joint destruction. Levels of
      S100A8/A9 serum protein were significantly enhanced (19%) at baseline in patients
      who had pronounced progression of joint destruction after 2 years. CONCLUSION:
      Our data suggest that the S100A8 and S100A9 proteins are crucially involved in
      synovial activation and cartilage destruction during OA and that high levels may
      predict joint destruction in humans with OA.

PMID- 22143923
TI  - Rotator cuff calcific tendinitis: does warm saline solution improve the short
      term outcome of double-needle US-guided treatment?
AB  - PURPOSE: To determine whether saline temperature influences procedure performance
      and outcome in patients undergoing ultrasonography (US)-guided lavage for the
      treatment of rotator cuff calcific tendinitis (RCCT). MATERIALS AND METHODS: This
      study was approved by the institutional review board, and informed consent was
      obtained from all patients. From December 2009 to May 2011, 462 patients (191 men
      and 271 women; mean age, 39.7 years) with painful RCCT diagnosed at US were
      prospectively enrolled and randomized into two groups. Operators subjectively
      classified calcifications as hard, soft, or fluid according to their appearance
      at US. US-guided percutaneous treatment of RCCT (local anesthesia, double-needle
      lavage, intrabursal steroid injection) was performed with warm saline (42 degrees
      C, 107 degrees F) in 229 patients and with room-temperature saline in 233.
      Operators and patients were not blinded to saline temperature. The ease of
      calcium dissolution was subjectively scored (easy=1, intermediate=2,
      difficult=3). Procedure duration was recorded. Patient discomfort was assessed by
      using a visual analog scale (VAS). The occurrence of postprocedure bursitis was
      recorded. Statistical analyses were performed with Mann-Whitney U, chi2, and
      analysis of variance tests. RESULTS: Procedure duration was significantly shorter
      (P<.001) in patients treated with warm saline (mean, 576 seconds+/-121) than in
      those treated with room-temperature saline (mean, 777 seconds+/-151). Calcium
      dissolution was significantly easier in patients treated with warm saline (median
      score, 1) than in those treated with room-temperature saline (median score, 2).
      Subgroup analysis according to calcification appearance at US showed a
      significant difference between groups for both soft (P=.003) and hard (P<.001)
      calcifications. No overall significant differences were found for VAS score (warm
      saline group: baseline=8.9+/-0.6, 1 month=4.7+/-0.6, 2 months=4.0+/-0.7, 3
      months=3.4+/-0.4, 1 year=3.0+/-0.7; room-temperature saline group: baseline=9.2+/
      0.4, 1 month=4.5+/-0.7, 2 months=4.1+/-0.9, 3 months=3.1+/-0.7, 1 year=3.2+/-0.8;
      P=.491). Postprocedural bursitis was observed in eight patients in the warm
      saline group and 20 in the room-temperature saline group (P<.022). CONCLUSION: In
      the treatment of RCCT, warm saline appears to reduce procedure duration and
      improve calcification dissolution while reducing the frequency of postprocedural
      bursitis.

PMID- 22143924
TI  - Accuracy of unenhanced MR imaging in the detection of axillary lymph node
      metastasis: study of reproducibility and reliability.
AB  - PURPOSE: To investigate the accuracy, reproducibility, and reliability of
      unenhanced magnetic resonance (MR) imaging techniques for detecting metastatic
      axillary lymph nodes in patients with newly diagnosed breast carcinoma. MATERIALS
      AND METHODS: Institutional review board approval and informed consent were
      obtained. Seventy-four consecutive women with invasive breast carcinoma were
      recruited to undergo preoperative breast MR imaging. Thirteen patients were
      excluded, two because they were undergoing preoperative chemotherapy and 11
      because of the presence of movement or susceptibility artifacts on images. Thus,
      61 patients (mean age, 53 years; range, 33-78 years) were included in this study.
      Axial T1-weighted MR images without fat saturation and diffusion-weighted (DW) MR
      images were analyzed by two experienced radiologists, who were blinded to the
      histopathologic findings. Visual and quantitative analyses of unenhanced MR
      images were performed. Sensitivity, specificity, and accuracy were calculated. To
      assess the intraobserver agreement, a second reading was performed. Statistical
      analysis was conducted on a patient-by-affected side basis. RESULTS: The
      sensitivity, specificity, and accuracy were 88%, 82%, and 85%, respectively, for
      axial T1-weighted MR imaging and 84%, 77%, and 80% for DW imaging. Apparent
      diffusion coefficients (ADCs) were significantly lower in the malignant group
      (P<.05 for all four readings), with the average of the four readings ranging from
      0.333*10(-3) mm2/sec to 2.843*10(-3) mm2/sec. The mean Lin coefficient comparing
      the mean ADC reading for each observer was 0.959 (95% confidence interval: 0.935,
      0.975), suggesting very high interobserver agreement between the two observers in
      terms of reproducibility of ADCs. The Bland-Altman plot showed good inter- and
      intraobserver agreement. CONCLUSION: Unenhanced MR imaging techniques showed high
      accuracy in the preoperative evaluation of axillary status in patients with
      invasive breast cancer. Results indicate reliable and reproducible assessment
      with DW imaging, but it is unlikely to be useful in clinical practice.

PMID- 22143925
TI  - Shoulder MR arthrography: intraarticular anesthetic reduces periprocedural pain
      and major motion artifacts but does not decrease imaging time.
AB  - PURPOSE: To prospectively determine whether the addition of an intraarticular
      anesthetic to the magnetic resonance (MR) arthrography solution has an effect on
      periprocedural pain, motion artifacts, and imaging time. MATERIALS AND METHODS:
      This study was approved by the institutional review board, and written informed
      consent was obtained from all patients. From September 2009 to March 2010, 127
      patients, most imaged for shoulder pain, were randomized into two groups. The
      first group (group A, 63 patients) received intraarticular injection of
      gadopentetate dimeglumine, ropivacaine 0.5%, and normal saline in a ratio of
      1:100:100. The second group (group B, 64 patients) received intraarticular
      injection of gadopentetate dimeglumine and normal saline in a ratio of 1:200.
      Pain was assessed before and after injection and immediately after 1.5-T MR
      imaging and rated on a scale of 0 to 10. Motion artifact was assessed by two
      musculoskeletal radiologists and two fellows by using a scale of 0 to 3 (0=no
      artifact, 1=artifact present but not affecting diagnostic image quality,
      2=artifact present and diminishing diagnostic image quality, and 3=artifact
      present and rendering image nondiagnostic). MR imaging time and examinations with
      repeated sequences were recorded. Wilcoxon rank sum, analysis of covariance, and
      permutation data analyses were performed. RESULTS: The mean pain levels before
      injection, after injection, and after MR imaging were 3.5, 2.3, and 2.5,
      respectively, for group A and 3.6, 3.1, and 3.2 for group B. After adjusting for
      age, sex, and preinjection pain level, the mean differences in pre- and
      postinjection pain and preinjection pain and post-MR imaging pain between the two
      groups were -0.9 (P=.017) and -0.8 (P=.056), respectively. No significant
      difference in mean total MR imaging time or number of patients with repeat
      sequences was noted. Radiologists 1 and 2 recorded grade 2 or 3 motion in six and
      five patients, respectively, in group A and 15 and 14 patients, respectively, in
      group B (P=.047 and .048, respectively). Radiologists 3 and 4 recorded grade 2 or
      3 motion in 13 and 23 patients, respectively, in group A and 23 and 33 patients,
      respectively, in group B (P=.093 and .110, respectively). CONCLUSION: The use of
      an intraarticular anesthetic significantly reduces periprocedural pain and major
      motion artifacts associated with MR shoulder arthrography; however, total MR
      imaging time is not reduced.

PMID- 22143926
TI  - High-b-value diffusion-weighted MR imaging of benign hepatocellular lesions:
      quantitative and qualitative analysis.
AB  - PURPOSE: To analyze the signal intensity (SI) of benign hepatocellular lesions in
      high-b-value diffusion-weighted (DW) magnetic resonance (MR) images and to
      compare the apparent diffusion coefficient (ADC) values of focal nodular
      hyperplasias (FNHs) with those of hepatocellular adenomas (HCAs). MATERIALS AND
      METHODS: This retrospective study was approved by institutional review board,
      with waiver of informed consent. Inclusion criteria were consecutive patients
      with diagnosed FNH or HCA who underwent MR imaging with a DW sequence of the
      liver at three b values, 0, 150, and 600 sec/mm2. The final study population
      included 67 patients (seven men, 60 women) with 90 hepatocellular lesions (54
      FNHs, 36 HCAs). The mean ADC was compared between the lesions and the liver.
      Receiver operating characteristic analysis was performed to evaluate the
      diagnostic value of ADC for differentiating HCAs and FNHs. RESULTS: The mean ADC
      value of all FNHs and HCAs was significantly lower than that of the liver
      (P=.004). An ADC ratio below 15% was observed in 50 of 54 (93%) FNHs and in 29 of
      36 (81%) HCAs. The mean ADC value of FNHs was significantly higher than that of
      HCAs (P<.001). The area under the receiver operating characteristic curve was
      0.760. With a cutoff value of 1.37*10(-3) mm2/sec, the sensitivity and
      specificity for differentiating HCA from FNH were 70% and 76%, respectively.
      There was no significant difference in ADC values between HCA subtypes. The SI of
      most FNHs and HCAs (78 of 90, 87%) increased with increasing b values, whereas
      none showed a decrease in SI with increasing b values. When the DW MR criteria
      for benign and malignant liver tumors were applied, 44 of 90 (49%) lesions would
      have been considered malignant lesions, whereas the other lesions (46 of 90, 51%)
      would have been considered indeterminate. CONCLUSION: On DW MR images, benign
      hepatocellular lesions often show findings that suggest restricted diffusion.

PMID- 22143927
TI  - Digital subtraction CT angiography for detection of intracranial aneurysms:
      comparison with three-dimensional digital subtraction angiography.
AB  - PURPOSE: To evaluate the diagnostic accuracy of digital subtraction computed
      tomographic (CT) angiography in the detection of intracranial aneurysms compared
      with three-dimensional (3D) rotational digital subtraction angiography (DSA), as
      reference standard, in a large cohort in a single center. MATERIALS AND METHODS:
      The study was waived by the institutional review board because of its
      retrospective nature. A total of 513 patients clinically suspected of having or
      with known intracranial aneurysms and other cerebral vascular diseases underwent
      both digital subtraction CT angiography with a dual-source CT scanner and 3D DSA,
      with a median interval of 1 day; 436 patients (84.9%) had acute subarachnoid
      hemorrhage at presentation. The sensitivity, specificity, and accuracy of digital
      subtraction CT angiography in depicting aneurysm were analyzed on a per-patient
      and per-aneurysm basis, with 3D DSA as the reference standard. The sensitivity,
      specificity, and accuracy of digital subtraction CT angiography in depicting
      aneurysms of different diameter (ie, <3 mm, 3-5 mm, 5-10 mm, and >10 mm) and of
      aneurysms at different locations in the anterior and posterior circulation were
      calculated. Kappa statistics were calculated to quantify inter- and intrareader
      variability in detecting aneurysms by using digital subtraction CT angiography
      for 100 patients. RESULTS: Of 513 patients, 106 (20.7%) had no aneurysms, while
      407 patients (79.3%) had 459 aneurysms at 3D DSA. Digital subtraction CT
      angiography correctly depicted 456 (99.3%) of the 459 aneurysms. By using 3D DSA
      as the standard of reference, the sensitivity and specificity of depicting
      intracranial aneurysms were 97.8% (398 of 407) and 88.7% (94 of 106),
      respectively, on a per-patient basis, and 96.5% (443 of 459) and 87.8% (94 of
      107), respectively, on a per-aneurysm basis. Digital subtraction CT angiography
      had sensitivities of 91.3% (42 of 46), 94.0% (140 of 149), 98.4% (186 of 189),
      and 100% (75 of 75) in depicting aneurysms of less than 3 mm, between 3 mm but
      less than 5 mm, between 5 mm but less than 10 mm, and 10 mm or greater,
      respectively, and of 95.8% (276 of 288) and 97.7% (167 of 171) in depicting
      anterior circulation and posterior circulation aneurysms, respectively. Excellent
      inter- and intrareader agreement was found on a per-patient (kappa=0.900 and
      0.939, both P<.001) and per-aneurysm basis (kappa=0.846 and 0.921, both P<.001)
      for the detection of intracranial aneurysms with digital subtraction CT
      angiography. CONCLUSION: Digital subtraction CT angiography has a high
      sensitivity and specificity in depicting intracranial aneurysms with different
      sizes and at different locations, compared with 3D DSA.

PMID- 22143928
TI  - Cardiac gene therapy: from concept to reality.
AB  - Heart failure is increasing in incidence throughout the world, especially in
      industrialized countries. Although the current therapeutic modalities have been
      successful in stabilizing the course of heart failure, morbidity and mortality
      remain quite high and there remains a great need for innovative breakthroughs
      that will offer new treatment strategies for patients with advanced forms of the
      disease. The past few years have witnessed a greater understanding of the
      molecular underpinnings of the failing heart, paving the way for novel strategies
      in modulating the cellular environment. As such, gene therapy has recently
      emerged as a powerful tool offering the promise of a new paradigm for alleviating
      heart failure. Current gene therapy research for heart failure is focused on
      exploring potential cellular targets and preclinical and clinical studies are
      ongoing toward the realization of this goal. Efforts also include the development
      of sophisticated viral vectors and vector delivery methods for efficient
      transduction of cardiomyocytes.

PMID- 22143929
TI  - Proton pumping ATPase mediated fungicidal activity of two essential oil
      components.
AB  - This work evaluates the antifungal activity of two essential oil components
      against 28 clinical isolates (17 sensitive, 11 resistant) and 3 standard
      laboratory strains of Candida. Growth of the organisms was significantly effected
      in both solid and liquid media at different test compound concentrations. The
      minimum inhibitory concentrations (MICs) of Isoeugenol (compound 1) against 31
      strains of Candida ranged 100-250 MUg/ml and those of o -methoxy cinnamaldehyde
      (compound 2) ranged 200-500 MUg/ml, respectively. Insight studies to mechanism
      suggested that these compounds exert antifungal activity by targeting H(+)-ATPase
      located in the membranes of pathogenic Candida species. At their respective
      MIC(90) average inhibition of H(+)-efflux for standard, clinical and resistant
      isolates caused by compound 1 and compound 2 was 70%, 74%, 82% and 42%, 42% and
      43%. Respective inhibition of H(+)-efflux by fluconazole (5 MUg/ml) was 94%, 92%
      and 10%. Inhibition of H(+)-ATPase leads to intracellular acidification and cell
      death. SEM analysis of Candida cells showed cell membrane breakage and
      alterations in morphology. Haemolytic activity on human erythrocytes was studied
      to exclude the possibility of further associated cytotoxicity.

PMID- 22143930
TI  - Down-regulation of osteopontin expression by RNA interference affects cell
      proliferation and chemotherapy sensitivity of breast cancer MDA-MB-231 cells.
AB  - To determine the effect of the down-regulation of osteopontin (OPN) expression on
      the sensitivity of breast cancer cells to doxorubicin, a chemotherapeutic drug,
      OPN shRNA was used to transfect the OPN-positive breast cancer cell line MDA-MB
      231. The expression of OPN mRNA and protein was analyzed by RT-PCR and Western
      blotting, respectively. The cell cycle distribution and apoptosis were analyzed
      by flow cytometry. Transfected MDA-MB-231 cells were treated with different
      concentrations of doxorubicin. Growth of MDA-MB-231 cells and IC50 of doxorubicin
      were determined by MTT assay. Expression of OPN mRNA and OPN protein of cells
      transfected with OPN shRNA was significantly decreased when compared to the
      negative controls (P<0.05). The number of MDA-MB-231 cells in the S phase was
      significantly increased, from 22.77 to 43.67%. Transfection increased apoptosis
      from 3.61 to 4.91%. Furthermore, the proliferation of MDA-MB-231 cells
      transfected with OPN shRNA was significantly decreased when compared to the
      negative control (transfected with empty vector). Sensitivity of MDA-MB-231 cells
      to doxorubicin was enhanced after treatment with OPN shRNA. The IC50 values of
      doxorubicin of the OPN-transfected group, the MDA-MB-231 cells and the negative
      transfected group were 0.13588, 0.83869 and 0.79652 ug/ml, respectively. Down
      regulation of OPN significantly inhibits expression of OPN protein in MDA-MB-231
      breast cancer cells, reduces cell proliferation and increases their sensitivity
      to doxorubicin.

PMID- 22143931
TI  - Disparate clinicopathological correlations of p53 and Bcl-2 in colorectal cancer.
AB  - p53 and Bcl-2 (both regulators of cell apoptosis) have been considered to be
      involved in the initiation and progression of the colorectal tumorigenic process,
      respectively. In this study, we investigated their association with tumor stage
      and grade -both substantially affecting prognosis. Immunohistochemical assessment
      of p53 and Bcl-2 was retrospectively conducted (using DO-7 and Ca-124 monoclonal
      antibodies, respectively) in 119 surgically resected colorectal carcinomas, and
      the results were correlated to tumor stage and grade. The proportion of tumors
      positively stained was 70% for p53 and 46% for Bcl-2, whereas co-expression of
      both markers was observed in 28% of cases. Tumors exhibiting the highest p53
      staining (>60% stained cells) were more frequently found in disease stage IV
      (p=0.03), while Bcl-2 positivity showed a predilection for earlier stage (p=0.02)
      and better grade (p=0.028). The associations of both markers with stage, along
      with a reciprocal relationship between p53(+) and Bcl-2(+) tumors (p=0.02),
      stronger for cases with p53 staining >30% (p=0.007), remained significant only
      for distal tumors. The distinct correlations of p53 and Bcl-2 with disease
      progression and aggressiveness (being influenced by the extent of staining and
      tumor site) may be clinically useful in the determination of high-risk colorectal
      cancer cases.

PMID- 22143932
TI  - Neuropeptide Y innervation in the vaginal mucosa among patients with pelvic organ
      prolapse.
AB  - The purpose of this study was to explore the innervation of neuropeptide Y (NPY)
      in the anterior vaginal mucosa of menopausal patients suffering from pelvic organ
      prolapse (POP). To do this, we analyzed the distribution and expression of NPY
      and its correlation with the occurrence and development of POP. Changes in NPY
      abundance in the anterior vaginal mucosa were assessed by immunohistochemistry in
      tissue samples collected from 41 POP patients and 9 control subjects. We divided
      patients into 4 populations, designated POP IV-POP I, exhibiting decreasing
      levels of NPY innervation. Through multivariate regression analysis, the level of
      reduction in NPY innervation was shown to be associated with an increasing
      severity of POP disease in a statistically significant manner. In conclusion, our
      data reveal that as the symptoms of POP intensify, the expression of NPY in
      anterior vaginal mucosa decreases progressively. Menopause, in combination with
      stress urinary incontinence (SUI), results in a stronger effect on both nerve
      damage to the pelvic floor and NPY alteration, compared to other risk factors,
      such as parity and weight.

PMID- 22143933
TI  - Nitric oxide triggers apoptosis in A375 human melanoma cells treated with
      capsaicin and resveratrol.
AB  - Capsaicin and resveratrol are strong chemopreventive agents with promising human
      consumption safety records and anticarcinogenic activities. However, the
      mechanism by which they induce apoptosis in tumor cells remains to be defined. In
      this study, we examined the role of nitric oxide (NO*) during apoptosis induced
      by these agents in A375 human melanoma cells. Capsaicin and resveratrol, alone or
      in combination, inhibited cell growth and promoted apoptosis by the elevation of
      NO* in A375 cells. Increased NO* production following treatment stimulated p53
      and triggered mitochondrial apoptotic events by inducing conformational changes
      in Bax and Bcl-2 with subsequent release of cytochrome c and activation of
      caspase 9 and 3. Caspase 8 activation concurrently appeared to be mediated by
      death receptor processing and downstream caspases. Collectively, our data suggest
      that capsaicin and resveratrol activate the mitochondrial and death receptor
      pathways, working together to induce apoptosis in A375 cells, and indicate that
      NO* could be considered a potential target for improvement of the effectiveness
      of melanoma treatment.

PMID- 22143934
TI  - Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell
      renal cell carcinoma of the lung.
AB  - High immunohistochemical expression of carbonic anhydrase IX (CAIX) is found in
      clear cell renal cell carcinoma (ccRCC), but no studies have assessed CAIX in
      metastatic ccRCC (mccRCC) of the lung. As 75% of patients with mccRCC show lung
      involvement, characterization of protein expression in these lesions is
      warranted. This investigation analyzed CAIX immunohistochemical expression in
      pulmonary/pleural tumors including mccRCC (n = 22), mesothelioma (n = 19),
      squamous cell carcinoma (n = 27), small cell carcinoma (n = 9), and
      adenocarcinoma (n = 49), as well as other mesothelial lesions (n = 4). Membranous
      immunoreactivity was semiquantitatively evaluated for percent of cells stained
      and intensity. All cases of mccRCC (1+, 4.5%; 3+, 95.5%) and mesothelioma (2+,
      10.5%; 3+, 89.5%) expressed CAIX. Most cases of lung squamous cell carcinoma (0,
      11.1%; 1+, 25.9%; 2+, 22.2%; 3+, 40.7%) and small cell carcinoma were reactive
      (0, 11.1%; 1+, 22.2%; 2+, 33.3%; 3+, 33.3%), while CAIX was detected less
      frequently in pulmonary adenocarcinoma (0, 61.2%; 1+, 16.3%; 2+, 12.2%; 3+,
      10.2%). In addition, CAIX was positive in adenomatoid tumor (3+, 100%) and
      mesothelial hyperplasia (3+, 100%). We demonstrate that CAIX is sensitive for
      mccRCC within the lung and a novel immunohistochemical marker for mesothelial
      proliferations, notably mesothelioma. Variable immunoreactivity is present among
      primary pulmonary epithelial tumors. Knowledge of expression overlap between
      these entities may prevent an incorrect interpretation of immunohistochemical
      results, particularly when limited tissue is available. As new carbonic anhydrase
      inhibitors are being evaluated, testing additional tumors for CAIX may lead to
      novel treatment options.

PMID- 22143935
TI  - Personalized cancer medicine and the future of pathology.
AB  - In February 2011, a group of pathologists from different departments in Europe
      met in Zurich, Switzerland, to discuss opportunities and challenges for pathology
      in the era of personalized medicine. The major topics of the meeting were
      assessment of the role of pathology in personalized medicine, its future profile
      among other biomedical disciplines with an interest in personalized medicine as
      well as the evolution of companion diagnostics. The relevance of novel
      technologies for genome analysis in clinical practice was discussed. The
      participants recognize that there should be more initiatives taken by the
      pathology community in companion diagnostics and in the emerging field of next
      generation sequencing and whole genome analysis. The common view of the
      participants was that the pathology community has to be mobilized for stronger
      engagement in the future of personalized medicine. Pathologists should be aware
      of the challenges and the analytical opportunities of the new technologies.
      Challenges of clinical trial design as well as insurance and reimbursement
      questions were addressed. The pathology community has the responsibility to lead
      medical colleagues into embracing this new area of genomic medicine. Without this
      effort, the discipline of pathology risks losing its key position in molecular
      tissue diagnostics.

PMID- 22143936
TI  - Impact of HER-2 overexpression/amplification on the prognosis of gastric cancer
      patients undergoing resection: a single-center study of 1,036 patients.
AB  - BACKGROUND: Opinions regarding the impact of human epidermal growth factor
      receptor (HER)-2 overexpression or HER-2 amplification on the prognosis of
      gastric cancer patients are mixed. The present study attempted to clarify this
      issue by investigating a large cohort of surgical patients. METHODS: We
      investigated 1,036 gastric cancer patients undergoing curative-intent resection.
      Their surgical specimens were evaluated for HER-2 expression by
      immunohistochemistry (IHC), and those with HER-2 expression levels of 2+ were
      additionally subjected to fluorescence in situ hybridization (FISH). Data on
      demographic and clinicopathological features and relevant prognostic factors in
      these patients were analyzed. RESULTS: HER-2 positivity was noted in 64 (6.1%) of
      1,036 gastric cancer patients, including 46 patients whose HER-2 expression level
      was 3+ on IHC and 18 patients whose FISH results were positive. On univariate
      analysis, HER-2 positivity was more often associated with differentiated
      histology, intestinal type, and negative resection margins, whereas only
      differentiated histology was independently associated with HER-2 positivity in a
      logistic regression model. For stage I-IV gastric cancer, HER-2 was not a
      prognostic factor. In a subpopulation study, although HER-2 positivity emerged as
      a favorable prognostic factor for stage III-IV gastric cancer on univariate
      analysis, it failed to be an independent prognostic factor after multivariate
      adjustment. CONCLUSIONS: The prevalence of HER-2 positivity, determined using
      standardized assays and scoring criteria in a large cohort of gastric cancer
      patients after resection, was 6.1%. HER-2 positivity was phenotypically
      associated with differentiated histology. HER-2 is not an independent prognostic
      factor for gastric cancer.

PMID- 22143937
TI  - High thymidine kinase 1 (TK1) expression is a predictor of poor survival in
      patients with pT1 of lung adenocarcinoma.
AB  - In this study, we explore the association of thymidine kinase 1 (TK1) expression
      in tumour tissues with clinical pathological parameters and prognosis in patients
      with pathological T1 (pT1) lung adenocarcinoma. The expression of TK1 was studied
      by immunohistochemistry techniques in 80 patients with surgically resected pT1
      lung adenocarcinoma, retrospectively and at >10-year follow-up. Compared to
      patients with low TK1 expression [labelling index (LI) <25.0%], patients with
      high TK1 expression (LI >= 25.0%) showed significantly increased
      lymphatic/vascular permeation and lymph node involvement and higher stromal
      invasion grade and pathological stage, and a greater number of patients had a
      tumour size of 2.1 to 3.0 cm. The 5-year survival and the mortality during follow
      up for patients with high TK1 expression were significantly worse than that of
      patients with low TK1 expression. The prognoses of the cases with grade 0, grade
      1 and grade 2 stromal invasions were similar and were better than those of cases
      with grade 3. In patients with stromal invasion grade 3, the 5-year survival and
      the mortality during follow-up were significantly worse for patients with high
      TK1 compared to patients with low TK1 expression. Univariate analyses showed that
      stromal invasion and TK1 expression were significant prognostic factors, while in
      the multivariate analysis, TK1 expression and tumour stage were found to be
      independent prognostic factors, but not stromal invasion. This is the first study
      showing that TK1 expression in combination with stromal invasion is a more
      reliable prognostic factor than stromal invasion classification itself in
      patients with pT1 lung adenocarcinoma. TK1 expression enables a further
      classification of the patients and opens opportunities for improved treatment
      outcome.

PMID- 22143938
TI  - DNA methylation biomarkers for lung cancer.
AB  - Changes in DNA methylation patterns are an important characteristic of human
      cancer including lung cancer. In particular, hypermethylation of CpG islands is a
      signature of malignant progression. Methylated CpG islands are promising
      diagnostic markers for the early detection of cancer. However, the full extent
      and sequence context of DNA hypermethylation in lung cancer has remained unknown.
      We have used the methylated CpG island recovery assay and high-resolution
      microarray analysis to find hypermethylated CpG islands in squamous cell
      carcinomas (SCC) and adenocarcinomas of the lung. Each tumor contained several
      hundred hypermethylated CpG islands. In an initial microarray screen, 36 CpG
      islands were methylated in five of five (=100%) of the SCC tumors tested and 52
      CpG islands were methylated in at least 75% of the adenocarcinomas tested (n=8).
      Using sodium-bisulfite-based approaches, 12 CpG islands (associated with the
      BARHL2, EVX2, IRX2, MEIS1, MSX1, NR2E1, OC2, OSR1, OTX1, PAX6, TFAP2A, and ZNF577
      genes) were confirmed to be methylated in 85% to 100% of the squamous cell
      carcinomas and 11 CpG islands (associated with the CHAD, DLX4, GRIK2, KCNG3,
      NR2E1, OSR1, OTX1, OTX2, PROX1, RUNX1, and VAX1 genes) were methylated in >80% of
      the adenocarcinomas. From the list of genes that were methylated in lung
      adenocarcinomas, we identified the gene FAT4 and found that this gene was
      methylated in 39% of the tumors. FAT4 is the closest mammalian homologue of the
      Drosophila tumor suppressor Fat which is an important component of the Hippo
      growth control pathway. Many of these newly discovered methylated CpG islands
      hold promise for becoming biomarkers for the early detection of lung cancer.

PMID- 22143939
TI  - Localization of FOXP3-positive cells in renal cell carcinoma.
AB  - Regulatory T cells (Treg cells), which are lymphocyte subsets capable of
      suppressing immune responses, appear to play a crucial role in maintaining immune
      homeostasis and mediating peripheral tolerance. However, Treg cells also
      accumulate in cancer patients and have been implicated in tumor immune escape.
      The forkhead box P3 (FOXP3) transcription factor is currently regarded as the
      most specific and reliable marker for Treg cells in men. We investigated the
      frequency and characterized the distribution of FOXP3(+) cells in renal cell
      carcinoma (RCC) patients, focusing on the tumor microenvironment. FOXP3
      expression was assessed in kidney tissue samples from 32 RCC patients by reverse
      transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Both
      conventional and quantitative RT-PCR disclosed higher FOXP3 expression levels in
      RCC than in adjacent normal renal tissue. Immunohistochemical staining of FOXP3
      expressing cells confirmed the accumulation of FOXP3(+) cells in tumor tissue,
      particularly at the border between malignant and adjacent benign kidney tissues.
      Our findings indicate that Treg cells accumulate at the tumor invasion zone and
      could thus be part of an immune escape mechanism of RCC that promotes disease
      progression.

PMID- 22143941
TI  - Sugar-to-base correlation in nucleic acids with a 5D APSY-HCNCH or two 3D APSY
      HCN experiments.
AB  - A five-dimensional (5D) APSY (automated projection spectroscopy) HCNCH experiment
      is presented, which allows unambiguous correlation of sugar to base nuclei in
      nucleic acids. The pulse sequence uses multiple quantum (MQ) evolution which
      enables long constant-time evolution periods in all dimensions, an improvement
      that can also benefit non-APSY applications. Applied with an RNA with 23
      nucleotides the 5D APSY-HCNCH experiment produced a complete and highly precise
      5D chemical shift list within 1.5 h. Alternatively, and for molecules where the
      out-and-stay 5D experiment sensitivity is not sufficient, a set of out-and-back
      3D APSY-HCN experiments is proposed: an intra-base (3D APSY-b-HCN) experiment in
      an MQ or in a TROSY version, and an MQ sugar-to-base (3D APSY-s-HCN) experiment.
      The two 3D peak lists require subsequent matching via the N1/9 chemical shift
      values to one 5D peak list. Optimization of the 3D APSY experiments for maximal
      precision in the N1/9 dimension allowed matching of all (15)N chemical shift
      values contained in both 3D peak lists. The precise 5D chemical shift correlation
      lists resulting from the 5D experiment or a pair of 3D experiments also provide a
      valuable basis for subsequent connection to chemical shifts derived with other
      experiments.

PMID- 22143942
TI  - Trichodinid (Ciliophora: Trichodinidae) Infections in Perch (Perca fluviatilis)
      experimentally exposed to pulp and paper mill effluents.
AB  - Wild-caught European perch (Perca fluviatilis) were exposed in the laboratory to
      untreated bleached pulp and paper mill effluent in two separate experiments. The
      first experiment was conducted at 7-8 degrees C using effluent concentrations of
      5 and 10%, and the second experiment was conducted at ambient river temperature
      of 4-20 degrees C using an effluent concentration of 1%. Trichodinid ciliates
      were identified and enumerated at the end of the exposure using a mucus
      subsampling technique from gill and skin as well as a formalin immersion
      technique, which provided total counts on each fish. Four different trichodinid
      species were identified on the fish. Prevalence of infection, mean number, and
      mean density of Trichodina spp. decreased on fish exposed to effluents compared
      with controls. Prevalence of infection, mean number, and mean density of
      Trichodinella epizootica decreased on fish exposed to 5% and 10% effluents but
      increased on fish exposed to 1% effluents compared with controls. These results
      demonstrate that trichodinid ciliates vary in their susceptibility to at least
      certain types of contaminants and cautions against using trichodinids as
      environmental indicators without delineating species.

PMID- 22143940
TI  - An overview of targeted alpha therapy.
AB  - The effectiveness of targeted alpha-therapy (TAT) can be explained by the
      properties of alpha-particles. Alpha particles are helium nuclei and are ~8,000
      times larger than beta(-)-particles (electrons). When emitted from radionuclides
      that decay via an alpha-decay pathway, they release enormous amounts of energy
      over a very short distance. Typically, the range of alpha-particles in tissue is
      50-100 MUm and they have high linear energy transfer (LET) with a mean energy
      deposition of 100 keV/MUm, providing a more specific tumor cell killing ability
      without damage to the surrounding normal tissues than beta(-)-emitters. Due to
      these properties, the majority of pre-clinical and clinical trials have
      demonstrated that alpha-emitters such as (225)Ac, (211)At, (212)Bi, (213)Bi,
      (212)Pb, (223)Ra, and (227)Th are ideal for the treatment of smaller tumor
      burdens, micrometastatic disease, and disseminated disease. Even though these
      alpha-emitters have favorable properties, the development of TAT has been limited
      by high costs, unresolved chemistry, and limited availability of the
      radionuclides. To overcome these limitations, more potent isotopes, additional
      sources, and more efficient isotope production methods should be addressed.
      Furthermore, better chelation and labeling methods with the improvements of
      isotope delivery, targeting vehicles, molecular targets, and identification of
      appropriate clinical applications are still required.

PMID- 22143943
TI  - Influence of hydrological parameters on organohalogenated micropollutant
      (polybrominated diphenyl ethers and polychlorinated biphenyls) behaviour in the
      Seine (France).
AB  - The temporal dynamics of polybrominated diphenyl ethers (PBDEs) and
      polychlorinated biphenyls (PCBs) were investigated in a heavily urbanized river
      (Seine River, Paris, France) from November 2009 to May 2010. Pollutant
      concentrations were in the range of 0.2 to 3.8 ng l(-1) (median 1.1) and 0.4 to
      3.6 ng l(-1) (median 1.1) for ? tri-deca BDEs and ? 7PCBs, respectively. In
      addition, for both PBDEs and PCBs, the partitioning between the particulate and
      dissolved phases was investigated. Due to their low water solubility, PBDEs were
      mainly (>70%) bound to particles. In contrast, only 54% of ? 7PCBs occurred in
      the particulate phase, and their partitioning was influenced by the degree of
      chlorination. During the sampling period, PBDE/PCB fluxes were quite similar and
      ranged from 3 to 128 and from 6 to 125 g day(-1), respectively. The annual mass
      flow of PBDEs and PCBs was estimated to 10 kg for both. Contrary to PCBs and BDE
      209, the temporal evolution of ? tri-hepta BDEs was related to particulate
      organic matter content, which is controlled by river flow variations. This
      suggests that they exhibit different sources or behavior in the Seine River.

PMID- 22143944
TI  - Multiple sclerosis: long time modifications of seasonal differences in the
      frequency of clinical attacks.
AB  - Previous papers show different patterns of seasonal distribution of multiple
      sclerosis attacks. This paper compares long-time modifications. Salerno MS
      registry (Southern Italy), was reviewed, including 189 patients, age onset 12-51
      years (mean = 29.88, SD = 8.4), disease duration mean = 6.94 years (1-29),
      attacks mean = 4.5 (2-25, SD = 3.41). Data were stratified by decades. Number of
      events/month was analyzed by odds ratios and forecast modeling (ARIMA); means by
      ANOVA and post hoc tests, and correlations by multiple regression. We found 869
      relapses: J = 72, F = 48, M = 122, A = 75, M = 68, Jn = 59, Jl = 81, A = 74, S =
      63, O = 70, N = 72, D = 65. In 2001-2008 there was one significant peak (March);
      in 1991-2000 many (greatest = July), and in 1984-1990, one positive (June), one
      negative (April). Differences between 1990s and 2000s are significant. It is the
      first study addressing ultradecennal trends, and finding that the season
      distribution of MS attacks is significantly different: the study confirms
      frequency peaks in early spring and summer, but they are different in different
      decades. This significant ultra-decade difference might support hypotheses more
      linked to infections or toxic substances than to sunlight, UV, or similar.

PMID- 22143945
TI  - The prevalence of eating disorders (EDs) and comorbid psychiatric disorders in
      adolescents: a two-stage community-based study.
AB  - OBJECTIVE: The aims of this study were to determine the prevalence of eating
      disorders (EDs) in adolescents and the prevalence of comorbid psychiatric
      disorders in adolescents with EDs. METHOD: During stage 1 of the study the Eating
      Attitude Test (EAT) was administered to 2907 randomly selected adolescent
      students. During stage 2 of the study students with an EAT score >30 underwent a
      clinical interview and those diagnosed with an ED (based on DSM-IV criteria) were
      included in the ED group. The control group included students that were age- and
      sex-matched with the ED group, were not diagnosed with an ED, and had an EAT
      score <30. Psychiatric comorbidity in the ED and control groups was evaluated
      using the Structured Clinical Interview for DSM-III-R (outpatient and non-patient
      forms). Additionally, a demographic data form, the Beck Depression Inventory
      (BDI), and the Beck Anxiety Inventory (BAI) were administered to all the
      participants. RESULTS: In total, 68 (9 male and 59 female) of the 2907 students
      met the diagnostic criteria for an ED. Point prevalence rates were as follows:
      anorexia nervosa: 0.034%; bulimia nervosa: 0.79%: eating disorder not otherwise
      specified: 1.51%; binge eating disorder: 0.99%; any ED: 2.33%. None of the male
      participants were diagnosed with anorexia nervosa or bulimia nervosa. In all, 8
      male students were diagnosed with binge eating disorder. The prevalence of
      comorbid psychiatric disorders was higher in the ED group. Major depression was
      the most prevalent comorbid disorder in the ED group, followed by generalized
      anxiety disorder and social phobia. The body mass index, and BDI, BAI, and EAT
      scores were higher in the ED group than in the control group. CONCLUSION: The
      results of this study show that whereas the point prevalence rate for EDs among
      all the participants was 2.3%, it was 4.03% among the female participants.
      Moreover, ED not otherwise specified was the most prevalent ED, and binge eating
      disorder was the most common ED among the males. The prevalence rates in the
      present study are similar to those observed in Western countries, except for the
      prevalence rate for anorexia nervosa, which in the present study was lower. Major
      depression and generalized anxiety disorder were the most prevalent comorbid
      disorders in the ED group.

PMID- 22143946
TI  - The disrupted connection between cerebral hemispheres in schizophrenia patients:
      a diffusion tensor imaging study.
AB  - AIM: In schizophrenia, the disruption of the communication between two brain
      hemispheres has not been shown clearly in the anatomical aspect despite other
      studies with different modalities suggested so. In this study, the structural
      integrity and the variables affecting the structural integrity of the corpus
      callosum, which is the main connection between two hemispheres, was investigated
      via diffusion tensor imaging (DTI). METHODS: The participants were evaluated by
      SCID-I and symptoms of the patients were assessed with PANSS. DT images of 25
      schizophrenia patients and 17 healthy volunteers were acquired via 1.5 T MR.
      Fractioned Anisotropy (FA) values of two groups, measured on the DT images, were
      compared. RESULTS: It was found that fractioned anisotropy (FA) values were lower
      in the genu of the patients than the healthy controls; however, there was no
      difference between the FA values of the patients and the controls in the
      splenium. Moreover, a significant negative correlation between the splenium FA
      values and the antipsychotic medication doses; and a trend level negative
      correlation of splenium FA and PANSS scores were found. CONCLUSION: Corpus
      callosum is the most important structure that connects two frontal lobes. The
      hypothesis that posits the fundamental role of the disconnection of frontal lobes
      in schizophrenia is supported by the findings of this study.

PMID- 22143947
TI  - Comparing brain magnetic resonance spectroscopy findings of pediatric treatment
      naive obsessive-compulsive disorder patients with healthy controls.
AB  - OBJECTIVE: It is believed that biochemical alterations in different brain regions
      are involved in the pathophysiology of obsessive-compulsive disorder (OCD) in
      children and adolescents. The aim of this study was to explore possible metabolic
      variations between pediatric OCD cases and healthy controls in brain regions
      which were implicated in OCD pathophysiology. METHOD: Children and adolescents
      between 8 and 16 years of age with OCD (n:15) and case matched healthy controls
      (n:15) were recruited for the study. After detailed clinical and
      neuropsychological evaluations, all subjects underwent the multiregional magnetic
      resonance spectroscopy (MRS) procedure with a long echo time (TE:135). RESULTS:
      Significantly lower n-acetylaspartate (NAA) ratios in the left inferior frontal
      gyrus, right occipital grey matter, left anterior cingulate cortex and lower
      choline (Cho) ratios in right and left anterior cingulate cortex and higher Cho
      ratio in left lenticular nucleus was observed in the OCD group. Also we found a
      negative correlation between OCD duration and left insular cortex NAA/Cho ratio.
      CONCLUSION: We found significant metabolic alterations in the brain regions which
      were implicated in OCD pathophysiology. Lower NAA and Cho ratios in anterior
      cingulate cortex and lower NAA ratios in the left inferior fronyal gyrus
      containing lateral orbitofrontal cortex can be possibly related to higher
      activation in OCD patients. Also further studies of the occipital lobes and
      insula should be continued in OCD.

PMID- 22143948
TI  - The relationship between insight and clinical features in bipolar disorder.
AB  - OBJECTIVE: The aim of this study is to examine the relationship between insight
      dimensions and clinical features in bipolar disorder. METHOD: One hundred and
      four inpatients with bipolar disorder( manic or mixed episodes) diagnosed
      according to DSM-IV criteria participated in the study. Patients were evaluated
      both during an acute episode and in remission, prior their discharge from the
      hospital by the Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression
      Rating Scale (MADRS), Positive and Negative Syndrome Scale (PANSS), The Scale of
      Unawareness of Mental Disorders (SUMD), and a questionnaire regarding demographic
      and clinical characteristics. RESULTS: In remission, 57 patients (54.8%) had
      insight of their illness while 14 (13.5%)did not have insight. Besides  %6.7 of
      patients did not have the Insight into the effects of medication. We also found
      that 27.9% of patients were unaware of the social consequences of their illness.
      Patients with psychotic symptoms had a significantly low level of awareness to
      the effects of their medication as well as the severeness of their manic episode.
      We found an unawareness of delusion in these patients. In terms of all SUMD
      items, female patients had significantly poorer insight compared to men. No
      correlation was found between the number of hospitalizations, the number of
      episodes or the first episode type and insight dimensions. CONCLUSION: Lack of
      insight in bipolar disorder is not rare. The assesment of insight addresses
      different components of the illness and the treatment awareness. The severity of
      illness,  aggressive impulse control difficulties, psychotic symptoms especially
      the presence of delusions, female sex may be important predictors of impaired
      insight.

PMID- 22143949
TI  - Anger attacks in bipolar versus recurrent depression.
AB  - BACKGROUND: Research on anger attacks has been mostly limited to unipolar
      depression, and only a few studies have focused on anger attacks in bipolar
      depression. METHODOLOGY: In a cross-sectional study, 22 subjects with bipolar
      depression were compared to 22 subjects with recurrent unipolar depression using
      an anger attack questionnaire, irritability, depression and anxiety scale and
      quality of life scale. RESULTS: Anger attacks were present in 62.5% subjects with
      recurrent depression (RDD group) compared to 54.5% in subjects with bipolar
      depression (BD group), but the difference between the groups was not
      statistically significant. Also, there was no significant difference between the
      RDD and BD groups on the Irritability Depression and Anxiety Scale and WHOQOL
      Bref except that the BD group had a poorer quality of life (QOL) compared to the
      RDD group in the social relationship domain (t=-2.30, p<0.05). In the BD group,
      the subjects with anger attacks were older (t=2.77, p<0.05), had significantly
      higher scores on the Irritability-Outwards component of IDA (t=3.90, p<0.01) and
      shorter duration of illness (Mann Whitney Signed ranked value 20.00, p<0.01) and
      duration of treatment (Mann Whitney Signed ranked value 28.00, p<0.05) compared
      to BD group members without anger attacks. In the RDD group, the subjects with
      anger attacks had poor QOL in the social domain (t= -2.12, p<0.05), environmental
      domain (t=2.99, p=.01) and total (t=2.56, p<0.05) QOL compared to those without
      anger attacks. CONCLUSION: Anger attacks are equally prevalent in unipolar and
      bipolar depression, are not influenced by sociodemographic and clinical
      variables, and lead to comparable impact on the subjective QOL in both groups.

PMID- 22143950
TI  - Stress, self-perception and interpersonal style in patients with physical
      illnesses.
AB  - OBJECTIVE: This study aimed to investigate the role of self-perception,
      interpersonal style, and anger in the context of stress in patients with physical
      illnesses, including coronary artery disease, gastrointestinal disorders,
      dermatological disorders, and diabetes. MATERIALS AND METHODS: The study sample
      included patients with physical illnesses (n = 124) and healthy controls (n =
      209). Symptoms of stress, self-perception, interpersonal style, and anger were
      evaluated using the Stress Symptoms Scale, Social Comparison Scale, Interpersonal
      Style Scale, and Multidimensional Anger Questionnaire, respectively. The role of
      self-perception, interpersonal style, and anger in stress experienced in the
      patients and controls was compared. RESULTS: The patients had higher stress
      symptoms, perceived themselves more negatively, had more problematic
      interpersonal styles, and more intense anger than the controls. The higher stress
      symptoms in the patients and the lower symptoms in the controls was predicted by
      4 common variables3/4dissatisfaction with life, dissatisfaction with
      interpersonal relationships, negative self-perception, and aggressive expression
      of anger. Another predictive variable in the psychosomatic group was age, whereas
      in the control group gender and internalized anger were predictive variables.
      CONCLUSION: As the physical illnesses had by those in the patient group are
      stress-related, inclusion of psychosocial interventions in treatment protocols,
      such as communication skills, and stress and anger management training, and
      interventions aimed at increasing a positive self-perception might improve their
      QoL.

PMID- 22143951
TI  - Family to family support programs for the caregivers of schizophrenia patients: a
      systematic review.
AB  - AIM: This systematic review aims to analyze the family to family support programs
      provided for the families of the schizophrenic patients and there potential
      impact on caregivers. METHOD: The family to family support programs described by
      articles in Pubmed, Ovid, Cinahl, Wiley Interscience and Cochrane databases were
      reviewed. The database research was conducted in English using 5 keywords. Twelve
      studies were identified using this approach and are included in this review.
      FINDINGS: The caregivers who participated in the family to family support
      programs reported a significant decrease in their burden and increase in social
      support and family function. Moreover, it was noted that there was an increase in
      life satisfaction and a decrease in the need for education of the caregivers who
      participated in the programs. RESULTS: All studies included in this review agreed
      that family to family support programs for the caregivers of schizophrenia
      patients had positive outcomes. Additionally, these studies suggested that
      systematic, planned and sustainable educational programs be developed for the
      caregivers of schizophrenic patients in order to help the caregivers cope with
      the challenges they encounter during the treatment procedures.

PMID- 22143952
TI  - Schizophrenia or frontotemporal dementia in a young Chinese female: a purview of
      possible diagnoses.
AB  - Frontotemporal dementia (FTD) is now increasingly being recognized as one of the
      causes of young onset dementia (YOD). The presentation of FTD can be subtle with
      a broad range of symptoms. This frequently causes misdiagnosis and a delay in
      initiating the correct treatment. While subtle personality changes, disinhibition
      and problems in executive functioning are frequently encountered in FTD, frank
      psychotic symptoms resembling schizophrenia are unusual. This is a case of a 38
      year old Chinese female that highlights how obsessive compulsive symptoms which
      progressed to florid psychosis and disorganized speech and behavior can be a
      presenting picture in FTD. For seven years, this patient was treated as a case of
      schizophrenia and was thought to have poor response to electroconvulsive therapy
      (ECT) as well as antipsychotic medication. Her blood work and
      electroencephalogram (EEG) were normal. Magnetic resonance imaging (MRI) showed
      progressive cerebral atrophy. This case report suggests that psychosis should be
      investigated in detail especially when the clinical presentation is not typical
      of a functional disorder and more so when the patient is not responsive to
      conventional treatment. This report also highlights the importance of eliciting
      symptoms suggestive of an "organic" etiology, such as incontinence and
      disorientation. In addition, the usefulness of repeated imaging to show the
      rapidly progressive course of FTD has been illustrated. Other possible
      differential diagnoses of this patient are also discussed.

PMID- 22143954
TI  - [Editorial].

PMID- 22143953
TI  - Aripiprazole augmentation treatment in treatment resistant bipolar depression:
      two patient reports.
AB  - It is known that in patients with bipolar disorder, depressive episodes last
      longer than mixed or manic/hypomanic episodes and there are reports detailing the
      difficulties confronted in its treatment. The concept of treatment resistant
      depression in bipolar disorder has not been as well described as that in
      treatment resistant unipolar depression. Here we present two patients with
      treatment resistant bipolar depression. The first patient in our study is a 51
      year old woman whose diagnoses were bipolar disorder, depressive episode and
      multiple sclerosis (in remission with interferon treatment) at the time of
      augmentation with aripiprazole. The second patient is a 43 year old woman with
      bipolar disorder, depressive disorder without any comorbid illness at the time of
      augmentation with aripiprazole. Aripiprazole was administered variably between 20
      30mg/daily based on tolerability and efficacy. In both cases, depression was
      assessed using the Hamilton Depression Rating scale (HDRS). Both patients
      responded to aripiprazole augmentation treatment. The effect of aripiprazole on
      bipolar depression needs to be further evaluated in double blind controlled
      studies. However, augmentation with aripiprazole in bipolar patients may be a
      future routine treatment for treatment resistant bipolar depression.    In this
      report, treatment of refractory bipolar depression and the efficacy of
      aripiprazole augmentation treatment in bipolar depression are discussed through
      two patients in depressive episode who remitted with aripiprazole augmentation.

PMID- 22143955
TI  - HOXC10 is overexpressed in breast cancer and transcriptionally regulated by
      estrogen via involvement of histone methylases MLL3 and MLL4.
AB  - HOXC10 is a critical player in the development of spinal cord, formation of
      neurons, and associated with human leukemia. We found that HOXC10 is
      overexpressed in breast cancer and transcriptionally regulated by estrogen
      (17beta-estradiol, E(2)). The HOXC10 promoter contains several estrogen response
      elements (ERE1-7, half-sites). A luciferase-based reporter assay showed that ERE1
      and ERE6 of HOXC10 promoter are E(2) responsive. ERalpha and ERbeta play critical
      roles in E(2)-mediated activation of HOXC10. Knockdown of ERalpha and ERbeta
      downregulated E(2)-induced HOXC10 expression. ERalpha and ERbeta bind to ERE1 and
      ERE6 regions in an E(2)-dependent manner. Additionally, knockdown of histone
      methylases MLL3 and MLL4 (but not MLL1 and MLL2) diminished E(2)-induced
      expression of HOXC10. MLL3 and MLL4 were bound to the ERE1 and ERE6 regions of
      HOXC10 promoter in an E(2)-dependent manner. Overall, we demonstrated that HOXC10
      is overexpressed in breast cancer, and it is an E(2)-responsive gene. Histone
      methylases MLL3 and MLL4, along with ERs, regulate HOXC10 gene expression in the
      presence of E(2).

PMID- 22143956
TI  - Design of multifunctional micelle for tumor-targeted intracellular drug release
      and fluorescent imaging.

PMID- 22143957
TI  - Malondialdehyde, Bcl-2, superoxide dismutase and glutathione peroxidase may
      mediate the association of sonic hedgehog protein and oxidative stress in autism.
AB  - Sonic hedgehog signaling and brain-derived neurotrophic factor play a neuro
      protective role against oxidative stress in autism. Sonic hedgehog also increases
      Bcl-2 expression and the activities of superoxide dismutase and glutathione
      peroxidase. The level or activity of Bcl-2, brain-derived neurotrophic factor,
      and the activities of superoxide dismutase and glutathione peroxidase are
      decreased in autism. Sonic hedgehog also decreases the production of
      malondialdehyde that its level is high in autism. Therefore, it is supposed that
      sonic hedgehog may be associated with oxidative stress in autism through other
      pathways too.

PMID- 22143958
TI  - Legg-Calve-Perthes disease in the UK: geographic and temporal trends in incidence
      reflecting differences in degree of deprivation in childhood.
AB  - OBJECTIVE: Little is known about Legg-Calve-Perthes disease, a common childhood
      precursor to osteoarthritis of the hip. This study was undertaken to analyze the
      incidence of Legg-Calve-Perthes disease in the UK, with respect to geographic and
      temporal trends over a 19-year period. METHODS: The General Practice Research
      database was analyzed to identify incident cases between 1990 and 2008 in
      children ages 0-14 years. Incidence rates were calculated by year and by region
      (National Health Service Strategic Health Authority regions in England, and
      Scotland, Wales, and Northern Ireland), and the association with regional markers
      of deprivation examined. RESULTS: Over the 19-year period there was a dramatic
      decline in Legg-Calve-Perthes disease incidence, with annual rates among children
      0-14 years old declining from 12.2 per 100,000 to 5.7 per 100,000 (P < 0.001).
      There was also marked geographic variation, with incidence rates in Scotland more
      than twice those in London (10.39 [95% confidence interval 8.05-13.2] versus 4.6
      [95% confidence interval 3.4-6.1] per 100,000 0-14-year-olds). A more rapid
      decline in incidence was apparent in the Northern regions compared to Southern
      regions. The quintile with the highest degree of deprivation had the highest
      disease incidence (rate ratio 1.49 [95% confidence interval 1.10-2.04]) and, with
      the exception of London, regional incidence showed a strong linear relationship
      with regional deprivation score (P < 0.01). CONCLUSION: The incidence of Legg
      Calve-Perthes disease in the UK has a strong North-South divide, with a greater
      disease incidence within the Northern regions of the UK. There was a marked
      decline in incidence over the study period, which was more marked in Northern
      areas. The declining incidence, along with the geographic variation, suggests
      that a major etiologic determinant in Legg-Calve-Perthes disease is environmental
      and closely linked to childhood deprivation.

PMID- 22143959
TI  - QCT measures of bone strength at the thoracic and lumbar spine: the Framingham
      Study.
AB  - We used volumetric quantitative computed tomography (QCT) scans to evaluate
      volumetric bone density (vBMD), geometry, and strength in the thoracic (T8 to
      T10) and lumbar (L3 to L5) spine and determined how these parameters varied with
      age, sex, and spinal region. Participants included 690 participants of the
      Framingham Study, 40 to 87 years old (mean, 61 years). In both women and men,
      trabecular vBMD declined with age similarly for lumbar and thoracic regions,
      whereas cortical vBMD and integral vBMD, vertebral strength, and compressive
      force declined more at the lumbar spine than thoracic spine (interaction, p <
      0.01). Notably, in men, cortical vBMD increased (beta = 0.0004, p = 0.01), and
      vertebral strength did not change (beta = 1.9305, p = 0.66) at the thoracic spine
      with age. In both women and men, vertebral cross-sectional area increased less
      and the factor-of-risk increased more with age at the lumbar than at the thoracic
      region (interaction, p < 0.01). For example, in women, the factor-of-risk for
      forward flexion increased (worsened) with age 6.8-fold more in the lumbar spine
      (beta = 0.0157), compared with the thoracic spine (beta = 0.0023). vBMD and
      vertebral strength declined more and the factor-of-risk increased more with age
      in women than men (interaction, p < 0.01). For instance, integral vBMD for the
      lumbar spine declined 36% from 40 to 75 years of age in women compared with 18%
      in men. There was little or no age-related change in the forces applied to the
      thoracic vertebrae in either women or men. Age-related changes were greater in
      the lumbar spine than in the thoracic region and greater in women than men.
      Whereas women lost bone density and strength at both the thoracic and lumbar
      spine, in men, vertebral strength declined only at the lumbar spine. Our study
      confirms the importance of evaluating determinants of vertebral strength in both
      the thoracic and lumbar spine and in both women and men to understand mechanisms
      underlying the structural failure of vertebral bodies with aging.

PMID- 22143961
TI  - Journal of Gerontology: Medical Sciences. Welcome to 2012.

PMID- 22143960
TI  - HIV in Africa: Challenges and Directions for the Next Decade.
AB  - Africa carries a disproportionate burden of the global HIV endemic, accounting
      for two thirds of the global 33.3 million people living with HIV. While
      tremendous advances have been made in addressing the HIV epidemic in Africa,
      considerable challenges remain. Testing for HIV increased by 86% from 2007 to
      2009 but more than 75% of people 15-49 years remain unaware of their HIV status.
      CD4 count at diagnosis tends to be low and linkage to care and treatment is
      suboptimal. The scale-up of antiretroviral therapy is ongoing but is hampered by
      the lack of diagnostic capability to monitor response to therapy and a
      substantial healthcare workforce shortage. Prevention strategies such as male
      circumcision, pre-exposure prophylaxis, and antiretroviral therapy for prevention
      have generated great excitement but cost and healthcare infrastructure
      deficiencies may limit their widespread applicability. Operational research to
      validate and inform treatment decisions, health care policies, and prevention
      strategies is sorely needed.

PMID- 22143962
TI  - Ergosterol from the soilborne fungus Ganoderma boninense.
AB  - Ergosterol is the main component of the fungal membrane and is not found in
      plants or other microbial cells. Therefore, it can be a useful biomarker for the
      quantification of fungal biomass. We are now reporting the first isolation and
      characterisation of ergosterol from the mycelium of G. boninense. The ergosterol
      structure was detected by Thin Liquid Chromatography (TLC) and Ultra Performance
      Liquid Chromatography (UPLC) and confirmed with Gas Chromatography coupled with
      Mass Spectrometry (GCMS) and Nuclear Magnetic Resonance (NMR) analysis.

PMID- 22143963
TI  - The pH dependence of the total fluorescence of graphite oxide.
AB  - Graphite oxide was characterized by pH dependent excitation-emission matrices
      from 300 to 500 nm in excitation and from 320 to 600 nm in emission which reveal
      the presence of two pH steps. These are assigned to the presence of carboxy
      groups and phenolic hydroxy groups, respectively. Fluorescence is strongest at
      470 nm excitation and 555 nm emission. The fluorescence intensity is a function
      of pH but not of temperature, and is not quenched by oxygen.

PMID- 22143964
TI  - The pneumonectomy syndrome.

PMID- 22143965
TI  - Comparison of standard, prone and cine MRI in the evaluation of tethered cord.
AB  - BACKGROUND: Tethered cord syndrome (TCS) is defined by abnormal traction on the
      spinal cord that confines its movement. Surgical cord release usually stops
      neurological deterioration; therefore, early and accurate neuroradiological
      diagnosis is important. Supine MRI is the imaging modality of choice, but prone
      MRI and cine MRI can demonstrate cord movement. OBJECTIVE: We compared the
      diagnostic accuracies of standard MRI, prone MRI and cine MRI in patients with
      clinical suspicion of TCS and evaluated inter-reader reliability for MR imaging.
      MATERIALS AND METHODS: Children who underwent MRI for suspicion of TCS were
      retrospectively identified. Supine, prone and cine MRI studies were re-read by
      two pediatric neuroradiologists. Conus level, filum appearance and cord movement
      were documented. RESULTS: Thirteen of 49 children had tethered cord documented at
      surgery. Conus level had the highest diagnostic accuracy (sensitivity 69-77%,
      specificity 94%, positive predictive value 82-83%, negative predictive value 89
      92%, correct diagnosis 88-90%) and highest between-reader concordance (98%).
      Prone and cine MRI did not add to the accuracy of the supine imaging. CONCLUSION:
      Conus level provides the highest diagnostic accuracy and inter-reader reliability
      in TCS. Until a larger series is evaluated, it remains questionable whether prone
      or cine MRI provides enough additional diagnostic information to warrant routine
      use.

PMID- 22143966
TI  - Comparison of phenotypic methods and matrix-assisted laser desorption ionisation
      time-of-flight mass spectrometry for the identification of aero-tolerant
      Actinomyces spp. isolated from soft-tissue infections.
AB  - Aero-tolerant Actinomyces spp. are an under-recognised cause of cutaneous
      infections, in part because identification using conventional phenotypic methods
      is difficult and may be inaccurate. Matrix-assisted laser desorption ionisation
      time-of-flight mass spectrometry (MALDI-TOF MS) is a promising new technique for
      bacterial identification, but with limited data on the identification of aero
      tolerant Actinomyces spp. This study evaluated the accuracy of a phenotypic
      biochemical kit, MALDI-TOF MS and genotypic identification methods for the
      identification of this problematic group of organisms. Thirty aero-tolerant
      Actinomyces spp. were isolated from soft-tissue infections over a 2-year period.
      Species identification was performed by 16 s rRNA sequencing and genotypic
      results were compared with results obtained by API Coryne and MALDI-TOF MS. There
      was poor agreement between API Coryne and genotypic identification, with only 33%
      of isolates correctly identified to the species level. MALDI-TOF MS correctly
      identified 97% of isolates to the species level, with 33% of identifications
      achieved with high confidence scores. MALDI-TOF MS is a promising new tool for
      the identification of aero-tolerant Actinomyces spp., but improvement of the
      database is required in order to increase the confidence level of identification.

PMID- 22143967
TI  - First-trimester pyelonephritis is associated with later initiation of prenatal
      care: a retrospective cohort analysis.
AB  - We sought to determine the morbidity, frequency, and demographics of pregnant
      patients with pyelonephritis not yet receiving prenatal care compared with
      patients with prenatal care. We performed a retrospective cohort analysis of 254
      consecutive admissions for pyelonephritis from January 2004 to June 2007 at a
      single tertiary hospital comparing patients with prenatal care versus patients
      with no prenatal care. The sample size was adequate to detect a 1-day difference
      in length of admission between the two groups with an alpha of 0.05 and 80%
      power. Categorical variables were compared by Fisher exact test, and continuous
      variables were compared by the Wilcoxon rank sum or Kruskal-Wallis test. Of the
      254 cases, 35 (13.8%) occurred in women who had not established prenatal care.
      There was no difference in the primary outcome of hospital length of stay.
      Overall, 29 cases (11.4%) occurred prior to 12 weeks and of these, significantly
      more patients presented having not established prenatal care (18 versus 11, p <
      0.0001). The majority of cases of pyelonephritis that occur prior to 12 weeks are
      among women with no prenatal care. Although the U.S. Preventative Services Task
      Force guidelines advise screening urine culture at 12 to 16 weeks, these findings
      support initiating screening at an earlier gestational age.

PMID- 22143968
TI  - Early fetal echocardiography: ready for prime time?
AB  - The objective of this study was to examine the performance of early fetal
      echocardiography as a screening tool for major cardiac defects in a high-risk
      population. Fetal echocardiograms performed at 12 to 16 weeks were reviewed.
      Cases that did not undergo a follow-up echocardiogram at 18 to 22 weeks were
      excluded. Results of the early and follow-up echocardiograms were compared. Over
      a 4-year period, 119 early fetal echocardiograms were recorded. Of those, 81
      (68%) had follow-up fetal echocardiograms. Results of the early echocardiogram
      were normal in 77 of 81 (95.1%) cases. Of these, the follow-up was normal in 75
      of these 77 cases; in the remaining 2, the follow-up raised suspicion for a
      ventricular septal defect (VSD) in one and persistent left superior vena cava in
      the other. On the other hand, the early echocardiogram was abnormal in 4 (4.9%)
      cases: (1) atrioventricular canal defect, with the follow-up demonstrating a VSD;
      (2) hypoplastic right ventricle and transposition of the great arteries,
      confirmed on follow-up; (3) VSD and coarctation of the aorta, confirmed on follow
      up. In the fourth case, the early echocardiogram suspected a VSD and right-left
      disproportion, yet the follow-up was normal. In conclusion, early fetal
      echocardiography appears to be a reasonable screening tool for major cardiac
      defects.

PMID- 22143969
TI  - Therapeutic hypothermia during neonatal transport: current practices in
      California.
AB  - Therapeutic hypothermia initiated at <6 hours of age reduces death and disability
      in newborns >= 36 weeks' gestation with moderate to severe hypoxic ischemic
      encephalopathy. Given the limited therapeutic window, cooling during transport
      becomes a necessity. Our goal was to describe the current practice of therapeutic
      hypothermia during transport used in the state of California. All level III
      neonatal intensive care units (NICUs) were contacted to identify those units
      providing therapeutic hypothermia. An electronic questionnaire was sent to obtain
      basic information. Responses were received from 28 (100%) NICUs performing
      therapeutic hypothermia; 26 NICUs were cooling newborns and two were in the
      process of program development. Eighteen (64%) centers had cooled a patient in
      transport, six had not yet cooled in transport, and two do not plan to cool in
      transport. All 18 centers use passive cooling, except for two that perform both
      passive and active cooling, and 17 of 18 centers recommend initiation of cooling
      at the referral hospital. Reported difficulties include overcooling,
      undercooling, and bradycardia. Cooling on transport is being performed by
      majority of NICUs providing therapeutic hypothermia. Clinical protocols and
      devices for cooling in transport are essential to ensure safety and efficacy.

PMID- 22143970
TI  - Immunization with ovarian autoantigens leads to reduced fertility in mice
      following follicular dysfunction.
AB  - Immunoproteomics using sera of women with ovarian autoimmune diseases such as
      primary ovarian insufficiency and IVF embryo transfer recruits led to
      identification of three proteins namely alpha actinin 4 (alpha-ACTN4), heat-shock
      70 protein 5 (HSPA5), and actin beta (ACTB). This study deals with the
      establishment of a peptide ELISA for screening sera of antiovarian antibody (AOA)
      positive patients and further delves into understanding the role of these three
      proteins in ovarian autoimmunity in a mouse model. Using in silico approach,
      antigenic peptides of these proteins were identified and used for peptide ELISA.
      ELISA results indicated that AOA-positive sera showed reactivity with only
      specific peptides. The functional significance of the dominant peptides was
      studied by active immunization of female mice with these peptides. All immunized
      mice generated high antibody titers and profound effect on ovaries with few
      primordial (2.4+/-0.1, 2.4+/-0.2, and 2+/-0.1), primary (2.4+/-0.5, 1.7+/-0.3,
      and 2.4+/-0.3), preantral (2.3+/-0.5, 3.4+/-0.3, and 2.9+/-0.3), antral (0.9+/
      0.2, 1.6+/-0.8, and 2.3+/-0.6) follicles, and corpora lutea (2.8+/-0.8, 2.9+/
      1.7, and 4.6+/-2.3), and increased number of atretic follicles (5.5+/-0.4, 4.9+/
      1.8, and 7.5+/-1.0) in ACTN4-, HSPA5-, and ACTB-immunized mice compared with
      control animals (3.0+/-0.2, 3.5+/-0.6, 3+/-0.1, 3.6+/-0.2, 4.7+/-0.3, and 1.5+/
      0.3) respectively. These mice when mated with fertile male mice showed an overall
      25-43% reduction in fertility compared with controls. The data clearly suggest
      that the dominant antigenic epitopes of the three proteins play critical role in
      fertility and could possibly be the key autoimmune targets. These epitopes could
      be used to develop a more specific and sensitive diagnostic test for women with
      ovarian autoimmune diseases and to design therapy for disease management for
      reinstatement of ovarian function.

PMID- 22143971
TI  - Distribution of GFRA1-expressing spermatogonia in adult mouse testis.
AB  - In mice and other mammals, spermatogenesis is maintained by spermatogonial stem
      cells (SSCs), a cell population belonging to undifferentiated type A
      spermatogonia. In the accepted model of SSC self-renewal, Asingle (As)
      spermatogonia are the stem cells, whereas paired (Apaired (Apr)) and chained
      (Aaligned (Aal)) undifferentiated spermatogonia are committed to differentiation.
      This model has been recently challenged by evidence that As and chained (Apr and
      Aal), undifferentiated spermatogonia are heterogeneous in terms of gene
      expression and function. The expression profile of several markers, such as GFRA1
      (the GDNF co-receptor), is heterogeneous among As, Apr and Aal spermatogonia. In
      this study, we have analysed and quantified the distribution of GFRA1-expressing
      cells within the different stages of the seminiferous epithelial cycle. We show
      that in all stages, GFRA1+ chained spermatogonia (Apr to Aal) are more numerous
      than GFRA1+ As spermatogonia. Numbers of chained GFRA1+ spermatogonia are sharply
      reduced in stages VII-VIII when Aal differentiate into A1 spermatogonia. GFRA1
      expression is regulated by GDNF and in cultures of isolated seminiferous tubules,
      we found that GDNF expression and secretion by Sertoli cells is stage-dependent,
      being maximal in stages II-VI and decreasing thereafter. Using qRT-PCR analysis,
      we found that GDNF regulates the expression of genes such as Tex14, Sohlh1 and
      Kit (c-Kit) known to be involved in spermatogonial differentiation. Expression of
      Kit was upregulated by GDNF in a stage-specific manner. Our data indicate that
      GDNF, besides its crucial role in the self-renewal of stem cells also functions
      in the differentiation of chained undifferentiated spermatogonia.

PMID- 22143972
TI  - The slower the better: how sperm capacitation and acrosome reaction is modified
      in the presence of estrogens.
AB  - In order for mammalian sperm to obtain a fertilizing ability, they must undergo a
      complex of molecular changes, called capacitation. During capacitation, steroidal
      compounds can exert a fast nongenomic response in sperm through their interaction
      with plasma membrane receptors, and activate crucial signaling pathways leading
      to time-dependent protein tyrosine phosphorylation (TyrP). Estrogen receptor beta
      was detected in epididymal mouse sperm; therefore, the effect of 17B-estradiol,
      estrone, estriol, and 17A-ethynylestradiol on mouse sperm capacitation in vitro
      was investigated. The effect was evaluated by positive TyrP in sperm heads and in
      the whole sperm lysates. Simultaneously, the state of the acrosome after the
      calcium ionophore-induced acrosome reaction was assessed. Generally, estrogens
      displayed a time and concentration-dependent stimulatory effect on sperm TyrP
      during capacitation. In contrast, the number of sperm that underwent the acrosome
      reaction was lower in the experimental groups. It has been demonstrated that both
      natural and synthetic estrogens can modify the physiological progress of mouse
      sperm capacitation. The potential risk in the procapacitation effect of estrogens
      can also be seen in the decreased ability of sperm to undergo the acrosome
      reaction. In conclusion, the capacitating ability of sperm can be significantly
      lowered by increasing the level of estrogens in the environment.

PMID- 22143973
TI  - A metal-organic framework with highly polar pore surfaces: selective CO2
      adsorption and guest-dependent on/off emission properties.
AB  - A 3D porous Zn(II) metal-organic framework
      {[Zn(2)(H(2)dht)(dht)(0.5)(azpy)(0.5)(H(2)O)].4H(2)O} (1;
      H(2)dht=dihydroxyterphthalate, azpy=4,4'-azobipyridine) has been synthesised by
      employing 2,5-dihydroxyterephthalic acid (H(4)dht), a multidentate ligand and
      4,4'-azobipyridine by solvent-diffusion techniques at room temperature. The as
      synthesised framework furnishes two different types of channels: one calyx-shaped
      along the [001] direction and another rectangle-shaped along the [101] direction
      occupied by guest water molecules. The dehydrated framework,
      {[Zn(2)(H(2)dht)(dht)(0.5)(azpy)(0.5)]} (1') provides 52.7% void volume to the
      total unit-cell volume. The pore surfaces of 1' are decorated with unsaturated
      Zn(II) sites and pendant hydroxyl groups of H(2)dht linker, thereby resulting in
      a highly polar pore surface. The dehydrated framework 1' shows highly selective
      adsorption of CO(2) over other gases, such as N(2), H(2), O(2) and Ar, at 195 K.
      Photoluminescence studies revealed that compound 1 exhibits green emission
      (lambda(max)~530 nm) on the basis of the excited-state intramolecular proton
      transfer (ESIPT) process of the H(2)dht linker; no emission was observed in
      dehydrated solid 1'. Such guest-induced on/off emission has been correlated to
      the structural transformation and concomitant breaking and reforming of the
      OH...OCO hydrogen-bonding interaction in the H(2)dht linker in 1'/1.

PMID- 22143974
TI  - Evaluation of treatment response in patients with metastatic renal cell
      carcinoma: role of state-of-the-art cross-sectional imaging.
AB  - Recent advances in genetics and oncology have led to development of a wide array
      of molecular therapeutics in the management of patients with metastatic renal
      cell carcinoma. These drugs have revolutionized the treatment of advanced disease
      by significantly improving patient outcomes. State-of-the-art cross-sectional
      imaging techniques play a seminal role in the evaluation of treatment response by
      providing reproducible, objective data, thereby permitting accurate
      quantification of tumor burden. Evolving functional imaging techniques such as
      perfusion and diffusion studies continue to advance the technology beyond
      assessing changes in tumor size and morphology.

PMID- 22143975
TI  - Requirement of myeloid cell-specific Fas expression for prevention of systemic
      autoimmunity in mice.
AB  - OBJECTIVE: The death receptor Fas is a critical mediator of the extrinsic
      apoptotic pathway, and its role in mediating lymphoproliferation has been
      extensively examined. The present study was undertaken to investigate the impact
      of myeloid cell-specific loss of Fas. METHODS: Mice with Fas flanked by loxP
      sites (Fas(flox/flox) ) were crossed with mice expressing Cre under control of
      the murine lysozyme M gene promoter (Cre(LysM) ), which functions in mature
      lysozyme-expressing cells of the myelomonocytic lineage. The genotype for
      Cre(LysM) Fas(flox/flox)  mice was verified by polymerase chain reaction and flow
      cytometric analysis. Flow cytometric analysis was also used to characterize
      myeloid, dendritic, and lymphoid cell distribution and activation in bone marrow,
      blood, and spleen. Luminex-based assays and enzyme-linked immunosorbent assays
      were used to measure serum cytokine/chemokine and immunoglobulin levels. Renal
      damage or dysfunction was examined by immunohistochemical and immunofluorescence
      analysis. RESULTS: Cre(LysM) Fas(flox/flox)  mice exhibited a systemic lupus
      erythematosus (SLE)-like disease that included leukocytosis, splenomegaly,
      hypergammaglobulinemia, antinuclear autoantibody and proinflammatory cytokine
      production, and glomerulonephritis. Loss of Fas in myeloid cells increased levels
      of both Gr-1(low)  and Gr-1(intermediate)  blood monocytes and splenic
      macrophages and, in a paracrine manner, incited activation of conventional
      dendritic cells and lymphocytes in Cre(LysM) Fas(flox/flox)  mice. CONCLUSION:
      Taken together, these results suggest that loss of Fas in myeloid cells is
      sufficient to induce inflammatory phenotypes in mice, reminiscent of an SLE-like
      disease. Thus, Fas in myeloid cells may be considered a suppressor of systemic
      autoimmunity.

PMID- 22143976
TI  - Contrasting roles of leukemia inhibitory factor in murine bone development and
      remodeling involve region-specific changes in vascularization.
AB  - We describe here distinct functions of leukemia inhibitory factor (LIF) in bone
      development/growth and adult skeletal homeostasis. In the growth plate and
      developing neonate bones, LIF deficiency enhanced vascular endothelial growth
      factor (VEGF) levels, enlarged blood vessel formation, and increased the
      formation of "giant" osteoclasts/chondroclasts that rapidly destroyed the
      mineralized regions of the growth plate and developing neonatal bone. Below this
      region, osteoblasts formed large quantities of woven bone. In contrast, in adult
      bone undergoing remodeling osteoclast formation was unaffected by LIF deficiency,
      whereas osteoblast formation and function were both significantly impaired,
      resulting in osteopenia. Consistent with LIF promoting osteoblast commitment,
      enhanced marrow adipocyte formation was also observed in adult LIF null mice, and
      adipocytic differentiation of murine stromal cells was delayed by LIF treatment.
      LIF, therefore, controls vascular size and osteoclast differentiation during the
      transition of cartilage to bone, whereas an anatomically separate LIF-dependent
      pathway regulates osteoblast and adipocyte commitment in bone remodeling.

PMID- 22143977
TI  - Genome-wide transcriptomic analysis of cotton under drought stress reveal
      significant down-regulation of genes and pathways involved in fibre elongation
      and up-regulation of defense responsive genes.
AB  - Cotton is an important source of natural fibre used in the textile industry and
      the productivity of the crop is adversely affected by drought stress. High
      throughput transcriptomic analyses were used to identify genes involved in fibre
      development. However, not much information is available on cotton genome response
      in developing fibres under drought stress. In the present study a genome wide
      transcriptome analysis was carried out to identify differentially expressed genes
      at various stages of fibre growth under drought stress. Our study identified a
      number of genes differentially expressed during fibre elongation as compared to
      other stages. High level up-regulation of genes encoding for enzymes involved in
      pectin modification and cytoskeleton proteins was observed at fibre initiation
      stage. While a large number of genes encoding transcription factors (AP2-EREBP,
      WRKY, NAC and C2H2), osmoprotectants, ion transporters and heat shock proteins
      and pathways involved in hormone (ABA, ethylene and JA) biosynthesis and signal
      transduction were up-regulated and genes involved in phenylpropanoid and
      flavonoid biosynthesis, pentose and glucuronate interconversions and starch and
      sucrose metabolism pathways were down-regulated during fibre elongation. This
      study showed that drought has relatively less impact on fibre initiation but has
      profound effect on fibre elongation by down-regulating important genes involved
      in cell wall loosening and expansion process. The comprehensive transcriptome
      analysis under drought stress has provided valuable information on differentially
      expressed genes and pathways during fibre development that will be useful in
      developing drought tolerant cotton cultivars without compromising fibre quality.

PMID- 22143978
TI  - Use of a posterior pedicle nasal septum and floor mucoperiosteum flap to
      resurface the nasopharynx after endoscopic nasopharyngectomy for recurrent
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Endoscopic nasopharyngectomy is a new salvage treatment for locally
      recurrent nasopharyngeal carcinoma (NPC). However, how to resurface the
      nasopharyngeal defects in endoscopic endonasal approaches to avoid persistent
      postoperative headache, to the best of our knowledge, has not been reported.
      METHODS: From September 2009 to August 2010, we used a modified posterior pedicle
      nasal septum and floor mucoperiosteum flap (nasal septum and floor flap, NSFF)
      after endoscopic nasopharyngectomy in 12 patients with locally recurrent NPC.
      Most of the nasal septum and floor mucoperiosteum, except for the posterior
      pedicle, was harvested to cover the nasopharyngeal defects. RESULTS: All NSFFs
      successfully covered the entire nasopharyngeal defects and relined the
      nasopharynx with good functional recovery. The nasopharyngeal wounds recovered in
      28 days (range, 14 to 56 days), and the donor-site wounds recovered in 46.5 days
      (range, 24-84 days). No reconstruction-related complications or disease
      recurrences were observed. CONCLUSION: The NSFF is a safe and promising
      reconstructive option to resurface the nasopharyngeal defect after endoscopic
      nasopharyngectomy in patients with locally recurrent NPC.

PMID- 22143980
TI  - The effect of recessions on gambling expenditures.
AB  - This article examines the influence of the business cycle on expenditures of
      three major types of legalized gambling activities: Casino gambling, lottery, and
      pari-mutuel wagering. Empirical results are obtained using monthly aggregated US
      per capita consumption time series for the period 1959.01-2010.08. Among the
      three gambling activities only lottery consumption appears to be recession-proof.
      This series is characterized by a vast and solid growth that exceeds the growth
      in income and the growth in other gambling sectors. Casino gambling expenditures
      show a positive growth during expansions and no growth during recessions. Hence,
      the loss in income during recessions affects casino gambling. However, income
      shocks which are not directly related to the business cycle do not influence
      casino gambling expenditures. Pari-mutuel wagering displays an overall negative
      trend and its average growth rate is smaller than the growth in income,
      especially during recessions. The findings of this article provide important
      implications for the gambling industry and for local governments.

PMID- 22143981
TI  - The use of specially designed tasks to enhance student interest in the cadaver
      dissection laboratory.
AB  - Cadaver dissection is a key component of anatomy education. Unfortunately,
      students sometimes regard the process of dissection as uninteresting or
      stressful. To make laboratory time more interesting and to encourage discussion
      and collaborative learning among medical students, specially designed tasks were
      assigned to students throughout dissection. Student response and the effects of
      the tasks on examination scores were analyzed. The subjects of this study were
      154 medical students who attended the dissection laboratory in 2009. Four tasks
      were given to teams of seven to eight students over the course of 2 weeks of
      lower limb dissection. The tasks were designed such that the answers could not be
      obtained by referencing books or searching the Internet, but rather through
      careful observation of the cadavers and discussion among team members.
      Questionnaires were administered. The majority of students agreed that the tasks
      were interesting (68.0%), encouraged team discussion (76.8%), and facilitated
      their understanding of anatomy (72.8%). However, they did not prefer that
      additional tasks be assigned during the other laboratory sessions. When
      examination scores of those who responded positively were compared with those who
      responded neutrally or negatively, no statistically significant differences could
      be found. In conclusion, the specially designed tasks assigned to students in the
      cadaver dissection laboratory encouraged team discussion and collaborative
      learning, and thereby generated interest in laboratory work. However, knowledge
      acquisition was not improved.

PMID- 22143982
TI  - Apa is a trimeric autotransporter adhesin of Actinobacillus pleuropneumoniae
      responsible for autoagglutination and host cell adherence.
AB  - Actinobacillus pleuropneumoniae is the causative agent of porcine
      pleuropneumonia, and adherence to host cells is a key step in the pathogenic
      process. Although trimeric autotransporter adhesins (TAAs) were identified in
      many pathogenic bacteria in recent years, none in A. pleuropneumoniae have been
      characterized. In this study, we identified a TAA from A. pleuropneumoniae, Apa,
      and characterized the contribution of its amino acid residues to the adhesion
      process. Sequence analysis of the C-terminal amino acid residues of Apa revealed
      the presence of a putative translocator domain and six conserved HsfBD1-like or
      HsfBD2-like binding domains. Western blot analysis revealed that the 126 C
      terminal amino acids of Apa could form trimeric molecules. By confocal laser
      scanning microscopy, one of these six domains (ApaBD3) was determined to mediate
      adherence to epithelial cells. Adherence assays and adherence inhibition assays
      using a recombinant E. coli- ApaBD3 strain which expressed ApaBD3 on the surface
      of E. coli confirmed that this domain was responsible for the adhesion activity.
      Moreover, cellular enzyme-linked immunosorbent assays demonstrated that ApaBD3
      mediated high-level adherence to epithelial cell lines. Intriguingly,
      autoagglutination was observed with the E. coli- ApaBD3 strain, and this
      phenomenon was dependent upon the association of the expressed ApaBD3 with the C
      terminal translocator domain.

PMID- 22143983
TI  - Photopolymerized polypyrrole microvessels.
AB  - We report on the preparation of water-filled polymer microvessels through the
      photopolymerization of pyrrole in a water/chloroform emulsion. The resulting
      structures were characterized by complementary spectroscopic and microscopic
      techniques, including Raman spectroscopy, XPS, SEM, and TEM. The encapsulation of
      fluorescent, magnetic, and ionic species within the microvessels has been
      demonstrated. Confocal microscopy and fluorescence anisotropy measurements
      revealed that the encapsulated chromophore (Rhodamine 6G) resides within voids in
      the capsules; however, strong interaction of the dye with polypyrrole results in
      a measurable decrease in its rotational dynamics. Microvessels loaded with
      ferrofluid exhibit magnetic properties, and their structures can be directed with
      an external magnetic field. TEM measurements allowed imaging of individual
      nanoparticles entrapped within the vessels. The application of Cu(2+)-loaded
      microvessels as a transducer layer in all-solid-state ion-selective electrodes
      was also demonstrated.

PMID- 22143984
TI  - Frequency and prognostic impact of the aberrant CD8 expression in 5,523 patients
      with chronic lymphocytic leukemia.
AB  - BACKGROUND: In patients with chronic lymphocytic leukemia (CLL), aberrant
      expression of the T-lineage antigen CD8 was reported in low frequencies. The
      clinical impact of this phenomenon remains in discussion. METHODS: We analyzed
      5,523 patients with CLL (21-97 years) by multiparametric flow cytometry and
      performed fluorescence in situ hybridization (FISH), immunoglobulin heavy chain
      variable (IGHV) region mutational status analysis, and clinical outcome studies.
      RESULTS: CD8 was positive in 61/5,523 (1.1%) patients. ZAP-70 expression amounted
      to a mean of 25.4% in CD8-positive vs. 28.2% in CD8-negative cases (n.s.), CD38
      expression to a mean of 38.6% vs. 34.0% (n.s.). Cytogenetic alterations did not
      differ significantly [CD8-positive vs. CD8-negative: 13q deletion: 24/36 (66.7%)
      vs. 2,015/3,368 (59.8%); trisomy 12:7/35 (20.0%) vs. 487/3,357 (14.5%); 11q
      deletion: 6/35 (17.1%) vs. 360/3,354 (10.7%)]. A mutated IGHV status showed
      similar frequency in CD8-positive and CD8-negative cases (31/44; 70.5% vs.
      1,700/2,816; 60.4%; n.s.). CD8-positive patients had a shorter median time to
      treatment compared with CD8-negative patients (12.0 vs. 77.1 months, P = 0.008).
      In univariable Cox analysis, CD8-positivity adversely influenced median TTT (P =
      0.011). In multivariable analysis, the strongest parameters were hemoglobin level
      and mutated IGHV status (P < 0.001 for both) but CD8-positivity was still
      relevant (P = 0.074). CONCLUSIONS: This study confirms that CD8 expression is a
      recurrent albeit rare phenomenon in patients with CLL and suggests that CD8
      expression has an adverse prognostic impact. Therefore, CD8 expression should be
      further investigated for its potential to contribute to risk stratification in
      patients with CLL.

PMID- 22143985
TI  - Analysis of Tn antigenicity with a panel of new IgM and IgG1 monoclonal
      antibodies raised against leukemic cells.
AB  - CD175 or Tn antigen is a carbohydrate moiety of N-acetylgalactosamine
      (GalNAc)alpha1-O- linked to the residue of amino acid serine or threonine in a
      polypeptide chain. Despite the chemical simplicity of the Tn antigen, its
      antigenic structure is considered to be complex and the clear determinants of Tn
      antigenicity remain poorly understood. As a consequence, a broad variety of anti
      Tn monoclonal antibodies (mAbs) have been generated. To further investigate the
      nature and complexity of the Tn antigen, we generated seven different anti-Tn
      mAbs of IgM and IgG classes raised against human Jurkat T cells, which are Tn
      positive due to the low activity of T-synthase and mutation in specific chaperone
      Cosmc. The binding analysis of anti-Tn mAbs with the array of synthetic
      saccharides, glycopeptides and O-glycoproteins revealed unexpected differences in
      specificities of anti-Tn mAbs. IgM mAbs bound the terminal GalNAc residue of the
      Tn antigen irrespective of the peptide context or with low selectivity to the
      glycoproteins. In contrast, IgG mAbs recognized the Tn antigen in the context of
      a specific peptide motif. Particularly, JA3 mAb reacted to the GSPP or GSPAPP,
      and JA5 mAb recognized specifically the GSP motif (glycosylation sites are
      underlined). The major O-glycan carrier proteins CD43 and CD162 and isoforms of
      CD45 expressed on Jurkat cells were precipitated by anti-Tn mAbs with different
      affinities. In summary, our data suggest that Tn antigen-Ab binding capacity is
      determined by the peptide context of the Tn antigen, antigenic specificity of the
      Ab and class of the immunoglobulin. The newly generated anti-Tn IgG mAbs with the
      strong specificity to glycoprotein CD43 can be particularly interesting for the
      application in leukemia diagnostics and therapy.

PMID- 22143986
TI  - Femoral lengthening with lengthening over a nail has fewer complications than
      intramedullary skeletal kinetic distraction.
AB  - BACKGROUND: Lengthening over a nail and internal lengthening nails have been
      developed to minimize or eliminate patients' time wearing a frame during femur
      lengthening. However it is unclear whether either of these two approaches results
      in faster times to union or fewer complications over the other.
      QUESTIONS/PURPOSES: We asked which technique better achieved: (1) the lengthening
      goals, (2) the distraction rate control, (3) quality of the regenerate bone, (4)
      fewer complications, and (5) if SF-36 scores and American Academy of Orthopaedic
      Surgeons Lower Limb Module (AAOS LLM) scores differ in each treatment modality?
      METHODS: We retrospectively reviewed the records and radiographs of 11 patients
      who had 12 Intramedullary Skeletal Kinetic Distractor (ISKD) procedures between
      2002 and 2005, and 21 patients with 22 femoral lengthenings performed as
      lengthening over nail procedures between 2005 and 2009. Details such as leg
      length discrepancies, operative time, time of removal of the external fixator or
      ISKD, and any complications encountered were recorded. SF-36 and AAOS LLM scores
      also were compiled. The minimum followups for the ISKD and the lengthening over
      nail cohorts were 62 months (average, 76 months; range, 62-93 months) and 13
      months (average, 27 months; range, 13-38 months), respectively. RESULTS: We
      observed no difference in achieving the lengthening goals between the two
      procedures. Distraction was not well controlled in the ISKD group; the
      distraction rates were 1.7 mm per day for the fast group (distraction rate
      greater than 1 mm/day) and 0.84 mm per day for the slow group (less than 1
      mm/day). The lengthening over nail group had an average distraction rate of 0.88
      mm per day. One of 20 of the patients who had lengthening over a nail had
      complications requiring additional unanticipated surgeries whereas six of 12
      patients who had femoral lengthening in the ISKD group had such complications.
      CONCLUSIONS: Based on our observations, we believe the lengthening over nail
      technique for femoral lengthening is associated with fewer complications than the
      ISKD. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 22143987
TI  - Who's left? Symptoms of schizophrenia that predict clinical trial dropout.
AB  - A significant proportion of subjects drop out of medium to long-term clinical
      studies prior to trial completion. This may bias reported study outcomes and
      reduce the statistical power of analyses. There is therefore a need for
      researchers to better understand the characteristics of dropout populations to
      increase completion rates. Data from a set of participants recruited as part of a
      24-week placebo-controlled trial were used to determine the relationship between
      the five Lindenmayer factors of positive, negative, cognitive, anxiety/depression
      and excitement symptoms and dropout at trial completion. Results indicated that
      the rate of trial dropout was significantly predicted by scores on the negative
      Lindenmayer factor (X2 (6, N = 126) = 15.60, p < .05). By trial completion,
      participants with 'high' negative Lindenmayer scores dropped out at a rate of
      64%, whereas 'medium' and 'low' groups dropped out at 43% and 30%, respectively.
      No other relationship between symptom severity scores and dropout across the
      remaining Lindenmayer factors was found. These findings reflect important
      considerations for the future design of clinical trials involving people with
      schizophrenia and may also provide clues into treatment compliance issues more
      generally.

PMID- 22143988
TI  - The pattern-recognition receptor nucleotide-binding oligomerization domain-
      containing protein 1 promotes production of inflammatory mediators in rheumatoid
      arthritis synovial fibroblasts.
AB  - OBJECTIVE: Pattern-recognition receptors (PRRs), such as Toll-like receptors
      (TLRs) and nucleotide-binding oligomerization domain-containing protein 2 (NOD
      2), have been shown to contribute to the pathogenesis of rheumatoid arthritis
      (RA). The aim of this study was to analyze the expression, regulation, and
      function of the PRR NOD-1 in RA synovial fibroblasts (RASFs), and to examine its
      interaction with other PRRs. METHODS: Expression of NOD-1 was analyzed by
      immunohistochemistry in synovial tissue from RA patients, psoriatic arthritis
      patients, gout patients, and osteoarthritis (OA) patients. RASFs and human
      monocyte-derived macrophages (HMDMs) were stimulated with L-alanyl-gamma-D
      glutamyl-meso-diaminopimelic acid, palmitoyl-3-cysteine-serine-lysine-4, poly(I
      C), lipopolysaccharide, heat-inactivated bacteria, tumor necrosis factor alpha
      (TNFalpha), or interleukin-1beta (IL-1beta). Expression levels of IL-6, CCL5,
      matrix metalloproteinases (MMPs), NODs, and TLRs were measured by real-time
      reverse transcription-polymerase chain reaction and/or enzyme-linked
      immunosorbent assay. NOD-1 and NOD-2 were silenced with target-specific small
      interfering RNA. Phosphorylation of IL-1 receptor-associated kinase 1 (IRAK-1)
      was measured by Western blotting. RESULTS: Expression of NOD-1 protein was
      significantly increased in RA synovium compared to OA synovium. The basal
      expression of NOD-1 was similar in RASFs, OASFs, healthy control peripheral blood
      mononuclear cells, and healthy control HMDMs. Stimulation of RASFs with TLR-3 up
      regulated the expression of NOD-1. Expression of IL-6, CCL5, MMPs, TLR-2, and NOD
      2 was significantly up-regulated in RASFs by stimulation with the NOD-1 ligand. A
      synergistic effect on IL-6 production was observed in cells stimulated with NOD-1
      and TLR-2 ligands or NOD-1 and TLR-4 ligands. Silencing of NOD-1, but not NOD-2,
      decreased the levels of IL-6 in RASFs after stimulation with TLR-2 and IL-1beta,
      and blocked the phosphorylation of IRAK-1. CONCLUSION: NOD-1 is strongly
      expressed in different cell types in the synovial tissue of patients with RA.
      These results indicate that NOD-1, either alone or interacting with other
      inflammatory mediators, can play an important role in the chronic and destructive
      inflammation of the joints in RA.

PMID- 22143990
TI  - Clinico-histologic conferences: histology and disease.
AB  - Providing a context for learning information and requiring learners to teach
      specific content has been demonstrated to enhance knowledge retention. To enhance
      students' appreciation of the role of science and specifically histology in
      clinical reasoning, disease diagnosis, and treatment, a new teaching format was
      created to provide clinical context, promote integration and application of
      science knowledge, and to foster peer teaching and learning: the Clinico
      Histologic Conference (CHC) for the Mount Sinai School of Medicine Histology
      course. Teams of six students were each assigned specific disease processes and
      were charged with creating oral presentations and handouts that taught their
      classmates about the clinical manifestations, etiopathogeneses, diagnoses, and
      treatments of the assigned processes, along with comparisons of normal histology
      to the pathology of the disease. Each team also created four questions, some of
      which were used on Histology written examinations. The physician facilitator
      evaluated the presentation and handouts. About two-thirds of students agreed the
      CHC enhanced appreciation of the importance of histology, provided a context for
      integration and application of basic science to patient care and enhanced their
      ability to teach their peers. Student feedback demonstrated that the CHCs were
      successful in promoting teamwork, peer teaching, and the application of histology
      to diagnose diseases. The authors believe that teaching basic science content in
      this new format enhanced student learning and application of medical knowledge,
      and that this new teaching format can be adopted by other medical school courses.

PMID- 22143989
TI  - Pteridium aquilinum and its ptaquiloside toxin induce DNA damage response in
      gastric epithelial cells, a link with gastric carcinogenesis.
AB  - The multifactorial origin of gastric cancer encompasses environmental factors
      mainly associated with diet. Pteridium aquilinum-bracken fern-is the only higher
      plant known to cause cancer in animals. Its carcinogenic toxin, ptaquiloside, has
      been identified in milk of cows and groundwater. Humans can be directly exposed
      by consumption of the plant, contaminated water or milk, and spore inhalation.
      Epidemiological studies have shown an association between bracken exposure and
      gastric cancer. In the present work, the genotoxicity of P. aquilinum and
      ptaquiloside, including DNA damaging effects and DNA damage response, was
      characterized in human gastric epithelial cells and in a mouse model. In vitro,
      the highest doses of P. aquilinum extracts (40 mg/ml) and ptaquiloside (60
      MUg/ml) decreased cell viability and induced apoptosis. gammaH2AX and P53-binding
      protein 1 analysis indicated induction of DNA strand breaks in treated cells. P53
      level also increased after exposure, associated with ATR-Chk1 signaling pathway
      activation. The involvement of ptaquiloside in the DNA damage activity of P.
      aquilinum was confirmed by deregulation of the expression of a panel of genes
      related to DNA damage signaling pathways and DNA repair, in response to purified
      ptaquiloside. Oral administration of P. aquilinum extracts to mice increased
      gastric cell proliferation and led to frameshift events in intron 2 of the P53
      gene. Our data demonstrate the direct DNA damaging and mutagenic effects of P.
      aquilinum. These results are in agreement with the carcinogenic properties
      attributed to this fern and its ptaquiloside toxin and support their role in
      promoting gastric carcinogenesis.

PMID- 22143991
TI  - Double-balloon endoscopy versus magnet-imaging enhanced colonoscopy for difficult
      colonoscopies, a randomized study.
AB  - BACKGROUND AND STUDY AIMS: Studies have estimated that failure of cecal
      intubation occurs with conventional colonoscopy in up to 10 % of cases. Double
      balloon endoscopy (DBE) systems, magnetic endoscope imaging (MEI), and
      transparent cap have been shown to improve success rates for colonoscopy. This
      study evaluated the utility of DBE for complete examination of the colon compared
      with MEI plus cap (MEI-Cap) after incomplete or technically difficult colonoscopy
      in a randomized comparative manner. PATIENTS AND METHODS: A total of 94 patients
      with incomplete or technically difficult colonoscopy were randomly assigned to
      receive either DBE (n = 47) or colonoscopy with MEI-Cap (n = 47). The primary end
      point was cecal intubation rate within 30 minutes. Secondary end points included
      intubation time, pain score using a visual analog scale, abdominal pressure
      attempts, doses of sedative medication, and changes in patient position during
      colonoscopy. RESULTS: Patient characteristics were comparable in both groups.
      Cecal intubation rate within 30 minutes was significantly higher for DBE (45 /47,
      95.7 %) than for MEI-Cap (34 /47, 72.3 %) (P = 0.0049). Mean time to reach the
      cecum was significantly lower in the DBE group (13.0 +/- 5.3 minutes) than in the
      MEI-Cap group (16.4 +/- 4.8 minutes; P = 0.0003). No complications were
      encountered in either group.   CONCLUSION: DBE is more useful for complete
      examination of the colon than MEI-Cap in patients with incomplete or technically
      difficult colonoscopy.

PMID- 22143992
TI  - Site-specific control of N7-metal coordination in DNA by a fluorescent purine
      derivative.
AB  - A synthetic strategy that utilizes O6-protected 8-bromoguanosine gives broad
      access to C8-guanine derivatives with phenyl, pyridine, thiophene, and furan
      substituents. The resulting 8-substituted 2'-deoxyguanosines are push-pull
      fluorophores that can exhibit environmentally sensitive quantum yields (Phi=0.001
      0.72) due to excited-state proton-transfer reactions with bulk solvent. Changes
      in nucleoside fluorescence were used to characterize metal-binding affinity and
      specificity of 8-substituted 2'-deoxyguanosines. One derivative, 8-(2-pyridyl)-2'
      deoxyguanosine (2PyG), exhibits selective binding of Cu(II), Ni(II), Cd(II), and
      Zn(II) through a bidentate effect provided by the N7 position of guanine and the
      2-pyridyl nitrogen atom. Upon incorporation into DNA, 2-pyridine-modified guanine
      residues selectively bind to Cu(II) and Ni(II) with equilibrium dissociation
      constants (K(d)) that range from 25 to 850 nM; the affinities depend on the
      folded state of the oligonucleotide (duplex>G-quadruplex) as well as the identity
      of the metal ion (Cu>Ni?Cd). These binding affinities are approximately 10 to 1
      000 times higher than for unmodified metal binding sites in DNA, thereby
      providing site-specific control of metal localization in alternatively folded
      nucleic acids. Temperature-dependent circular-dichroism studies reveal metal
      dependent stabilization of duplexes, but destabilization of G-quadruplex
      structures upon adding Cu(II) to 2PyG-modified oligonucleotides. These results
      demonstrate how the addition of a single pyridine group to the C8 position of
      guanine provides a powerful new tool for studying the effects of N7 metalation on
      the structure, stability, and electronic properties of nucleic acids.

PMID- 22143993
TI  - Nutritional requirements and strain heterogeneity in Ashbya gossypii.
AB  - Colony radial growth rates and specific growth rates of three related Ashbya
      gossypii strains ATCC10895, IMI31268, MUCL29450 and an unrelated strain,
      CBS109.26, were measured on various carbon and nitrogen sources at pH 4.5 and pH
      6.5 to elucidate physiological growth requirements and strain differences. All
      strains grew on yeast extract or ammonium as nitrogen sources, but not on
      nitrate. Substantial growth at pH 4.5 was observed only on complex medium. D
      Glucose, glycerol and starch were utilised as carbon sources. Ethanol was
      produced during growth on glycerol. Conversion of xylose into xylitol
      demonstrates that the xylose reductase is active. Phenotypic differences between
      related strains were greater than expected. We demonstrate that A. gossypii
      utilizes ammonium as sole nitrogen source at pH 6.5, facilitating further
      physiological studies using chemically defined media in the future.

PMID- 22143994
TI  - The effect of intracellular amino acids on GSH production by high-cell-density
      cultivation of Saccharomyces cerevisiae.
AB  - The present paper studies the effects of precursor amino acids, i.e., L-glutamic
      acid (Glu), L-glycine (Gly), and L-cysteine (Cys), on the glutathione (GSH)
      production. The three amino acids were added during the fermentations. The GSH
      production was analyzed by gas chromatography-mass spectrometry (GC-MS). It was
      observed that the cell content of Cys reduced continually, Gly maintained a
      fairly constant concentration, while Glu remained at a high concentration
      compared with Cys and Gly. The synthesis of GSH was found to significantly
      increase after 28 h of fermentation upon addition of 6 mmol l(-1) of each of the
      three amino acids. Under these conditions, the GSH yields reached 2,250+/-50 mg
      l(-1) at 34 h from 1,050+/-50 mg l(-1) at 28 h. The GC-MS analyses on the effect
      caused by the addition of amino acids indicated that the addition of Glu was not
      necessary to improve the GSH production by high-cell-density cultivation of
      Saccharomyces cerevisiae. The addition of Cys or Gly individually enhances the
      production of GSH.

PMID- 22143995
TI  - Pretreatment of corn stover with twin-screw extrusion followed by enzymatic
      saccharification.
AB  - Pretreatment of biomass before subjecting it to enzyme saccharification is
      crucial with regards to facilitating access of enzyme to biomass. Extrusion, as a
      continuous and cost-effective pretreatment method, combines heating with high
      shear and mixing opening cell walls at the microscopic scale, thus largely
      increasing the specific surface area (SSA) of biomass for enzyme adsorption. The
      objective of this study was to examine the effect of extrusion as a pretreatment
      method and the underlying factors ruling the improvement of sugar yields. The
      optimum glucose, xylose, and combined sugar recoveries were 48.79%, 24.98%, and
      40.07%, respectively, at 27.5% moisture content and 80 rpm screw speed. These
      yields were 2.2, 6.6, and 2.6 times higher than those for untreated corn stover.
      X-ray diffraction analysis showed that the crystallinity index was not a good
      indicator of sugar yield. However, scanning electron microscopy showed that the
      cellulose network was exposed due to the destruction of the lignin sheath. The
      Langmuir adsorption model was shown to be an effective tool for the estimation of
      the SSA of corn stover. The SSA of pretreated samples was significantly amplified
      over the control, revealing that extrusion can open the cell wall at the
      microscopic scale, which was especially favorable on sugar yields.

PMID- 22143996
TI  - Changes in intramuscular fat, fatty acid profile and cholesterol content induced
      by zeranol implantation strategy in hair lambs.
AB  - BACKGROUND: The effect of zeranol implantation strategy on intramuscular fat,
      fatty acid profile and cholesterol content of the longissimus dorsi muscle of
      hair lambs was studied. Four treatments were tested: C, control group; Z12, 12 mg
      zeranol; Z24, 24 mg zeranol in a single application; and RZ12, 12 mg zeranol
      given twice. One-way analysis of variance was employed to estimate the effect of
      treatments (P < 0.05). To separate the effect of the mean, orthogonal contrasts
      were tested: C1, C versus Z12 + Z24 + RZ12; C2, Z12 versus Z24 + RZ12; and C3,
      Z24 versus RZ12. RESULTS: A decrease (P < 0.05) in intramuscular fat content was
      observed from implanting (C1 effect) and zeranol reimplantation (C3 effect).
      Implanted lambs exhibited an increase (P < 0.05) in monounsaturated fatty acids
      compared with control group (40.60% versus 35.35%). All contrasts were
      significant for the sum of n-6 and n-3, with values lower (P < 0.05) in the
      control (n-6: 0.84% and n-3: 1.38%) and higher in the RZ12 treatment (n-6: 7.55%
      and n-3: 14.9%). Cholesterol decreased by 78% with implantation and increasing
      the dose. CONCLUSION: The results indicate that it is possible to induce
      favorable changes in the fatty acid profile and cholesterol content using a
      zeranol implantation strategy on hair lambs.

PMID- 22143997
TI  - Efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR)
      monotherapy in patients with generalised anxiety disorder: an analysis of pooled
      data from three 8-week placebo-controlled studies.
AB  - OBJECTIVE: Prospectively planned pooled analysis evaluating efficacy and
      tolerability of acute quetiapine XR monotherapy in generalised anxiety disorder.
      METHODS: Data from three 10-week, randomised, double-blind, placebo-controlled
      studies of similar design were analysed. RESULTS: At Week 8, Hamilton Anxiety
      Rating Scale (HAM-A) total score significantly improved with quetiapine XR: least
      squares means change -13.31, p < 0.001 (50 mg/day, n = 452), -14.39, p < 0.001
      (150 mg/day, n = 673) and -12.50, p < 0.05 (300 mg/day, n = 444) versus -11.30
      placebo; significant (p < 0.001, n = 665) improvements versus placebo were
      observed with each dose at Week 1. Significant improvements versus placebo at
      Week 8 are as follows: HAM-A psychic symptom subscale, Montgomery-Asberg
      Depression Rating Scale total, Pittsburgh Sleep Quality Index global scores for
      all quetiapine XR doses; HAM-A response and remission rates, HAM-A somatic
      symptom subscale score, Clinical Global Impression-Severity of Illness total
      score, % patients with Clinical Global Impression-Improvement score <=2 with
      quetiapine XR 50 and 150 mg/day; and Quality of Life Enjoyment and Satisfaction
      Questionnaire short form % maximum total score with quetiapine XR 150 mg/day. In
      the quetiapine XR 50, 150 and 300 mg/day and placebo groups, 13.2%, 16.5%, 24.0%
      and 5.4% of patients discontinued because of an adverse event, and 1.9%, 1.4%,
      3.7% and 1.8% of patients experienced clinically significant changes in glucose.
      The most common adverse events with quetiapine XR included dry mouth, somnolence,
      sedation and constipation. CONCLUSION: Quetiapine XR monotherapy reduced the
      symptoms of generalised anxiety disorder, with improvement from Week 1. Adverse
      events were consistent with the known tolerability profile of quetiapine.

PMID- 22143999
TI  - Risk management: FIFA's approach for protecting the health of football players.
AB  - BACKGROUND: Sport and exercise have long-term health benefits, but there is also
      a risk that participants will sustain injuries and/or ill health from these
      activities. For this reason, international sports governing bodies have a
      responsibility to identify the risks that exist within their sport and to provide
      guidance to participants and other stakeholders on how these risks can be
      controlled within acceptable levels. PURPOSE: To demonstrate how Federation
      Internationale de Football Association (FIFA), as football's governing body, uses
      a risk management framework to identify, quantify, mitigate and communicate the
      risks of injury and ill health in football for men, women and children in all
      environments. METHOD: All the research papers published by FIFA's Medical
      Assessment and Research Centre (F-MARC) during the period 1994 to 2011 were
      reviewed and categorised according to an established sport-related risk
      management framework. CONCLUSIONS: F-MARC investigated and mitigated 17 areas of
      risk to footballers' health in a coherent and consistent approach through the
      process of risk management.

PMID- 22144000
TI  - The epidemiology of new versus recurrent sports concussions among high school
      athletes, 2005-2010.
AB  - OBJECTIVES: To compare new versus recurrent concussions with respect to
      constellation of symptoms, symptom severity, symptom resolution; evaluate
      potential subset differences with respect to gender and sport; and to compare
      mechanisms and activities associated with new versus recurrent concussions.
      METHODS: Sports-related injury and exposure data were collected for nine sports
      from 2005 to 2010 from 100 nationally representative US high schools. RESULTS:
      Nationally, an estimated 732,805 concussions occurred. Of these reported
      concussions, 13.2% were recurrent. The rate of new concussions was 22.2 per
      100,000 athletic exposures while the rate of recurrent concussions was 3.1 per
      100,000 athletic exposures (RR 7.23, 95% CI 6.39 to 8.17, p<0.001). While 0.6% of
      new concussion symptoms took >1 month to resolve, 6.5% of recurrent concussion
      symptoms took >1 month to resolve (IPR 10.35; 95% CI 4.62 to 23.16; p<0.001).
      Loss of consciousness was reported more often with recurrent (7.7%) than new
      concussions (4.4%) (IPR 1.76; 95% CI 1.02 to 3.03; p=0.043). A greater proportion
      of athletes sustaining recurrent concussions returned to play in >3 weeks (7.5%)
      or were medically disqualified (16.2%) than athletes sustaining new concussions
      (3.8%; IPR 1.95; 95% CI 1.01 to 3.77; p=0.047 and 2.9%; IPR 5.58; 95% CI 3.50 to
      8.88; p<0.001, respectively). The majority of new and recurrent concussions
      resulted from contact with another person (73.4% and 77.9%, respectively).
      CONCLUSIONS: Athletes sustaining recurrent concussions had longer symptom
      resolution times, were kept out of play longer and reported loss of consciousness
      more frequently than athletes sustaining new concussions. With the possibility of
      long-term impairment and other negative sequelae, proper management and
      prevention of concussions at the high school level is imperative.

PMID- 22144001
TI  - The sports concussion note: should SCAT become SCOAT?
AB  - Sports concussion research and clinical guidelines have evolved rapidly. The most
      recent concussion consensus statement and guidelines (Zurich, 2008) provided
      clinicians with the Sports Concussion Assessment Tool version 2 (SCAT2) as a
      clinical template for the assessment of acute concussion. For the subsequent
      serial examinations required for the complete assessment of the concussed
      athlete, SCAT2 may be inadequate. This paper describes the experience and
      suggestions of South African sports physicians in evolving a more comprehensive
      clinical evaluation tool and record of patient care, the Sports Concussion Office
      Assessment Tool.

PMID- 22144002
TI  - Planning and implementing a nationwide football-based health-education programme.
AB  - Communicable and non-communicable diseases place enormous social and economic
      burdens on developed and developing countries. Health education leading to
      changes in people's attitudes and behaviours remains the best approach for
      reducing the problem of communicable diseases while there is evidence that
      programmes providing regular physical exercise and advocating a controlled diet
      can reduce the prevalence of many non-communicable diseases. Hence, the delivery
      of health education and physical activity within a single coherent programme
      offers great potential for simultaneously addressing both health issues. Since
      2006, FIFA has developed and tested a novel football-based health-education
      programme for children entitled '11 for Health', which is aimed at increasing
      children's levels of physical activity while also delivering 11 simple health
      messages. When new interventions of this type are published in the scientific
      literature, it is often not possible to describe important background information
      about the project that could assist other researchers in developing and
      implementing similar programmes. This paper attempts to bridge this gap by
      describing the aims and objectives, organisation, planning, implementation and
      monitoring requirements needed to deliver FIFA's '11 for Health' programme, first
      as a pilot project and subsequently as a nationwide project, through a tripartite
      arrangement between FIFA, the national Football Association and the Government
      Ministries in Mauritius.

PMID- 22144003
TI  - Early change in thermal perception is not a driver of anticipatory exercise
      pacing in the heat.
AB  - AIM: Initial power output declines significantly during exercise in hot
      conditions on attaining a rapid increase in skin temperature when exercise
      commences. It is unclear whether this initial reduced power is mediated
      consciously, through thermal perceptual cues, or is a subconscious process. The
      authors tested the hypothesis that improved thermal perception (feeling cooler
      and more comfortable) in the absence of a change in thermal state (ie, similar
      deep-body and skin temperatures between spray conditions) would alter pacing and
      40 km cycling time trial (TT) performance. METHOD: Eleven trained participants
      (mean (SD): age 30 (8.1) years; height 1.78 (0.06) m; mass 76.0 (8.3) kg)
      completed three 40 km cycling TTs in standardised conditions (32 degrees C, 50%
      RH) with thermal perception altered prior to exercise by application of cold
      receptor-activating menthol spray (MENTHOL SPRAY), in contrast to a separate
      control spray (CONTROL SPRAY) and no spray control (CON). Thermal perception,
      perceived exertion, thermal responses and cycling TT performance were measured.
      RESULTS: MENTHOL SPRAY induced feelings of coolness and improved thermal comfort
      before and during exercise. Skin temperature profile at the start of exercise was
      similar between sprays (CON-SPRAY 33.3 (1.1) degrees C and MENTHOL SPRAY 33.4
      (0.4) degrees C, but different to CON 34.5 (0.5) degrees C), but there was no
      difference in the pacing strategy adopted. There was no performance benefit using
      MENTHOL SPRAY; cycling TT completion time for CON is 71.58 (6.21) min, for CON
      SPRAY is 70.94 (6.06) min and for MENTHOL SPRAY is 71.04 (5.47) min. CONCLUSION:
      The hypothesis is rejected. Thermal perception is not a primary driver of early
      pacing during 40 km cycling TT in hot conditions in trained participants.

PMID- 22144004
TI  - Precompetition medical assessment of referees and assistant referees selected for
      the 2010 FIFA World Cup.
AB  - BACKGROUND: Several proposals for preparticipation screening to detect risk
      factors for sudden cardiac death in sports have been published, but referees have
      been neglected in this respect. METHODS: A standardised precompetition medical
      assessment (comprising a general physical, orthopaedic and cardiac examination
      and blood analysis) was performed in all 90 referees and assistant referees
      selected for the 2010 Federation Internationale de Football Association World
      Cup. RESULTS: More than a third of the referees showed at least one pathological
      finding in cardiac examinations; however, all follow-up examinations proved to be
      normal. The relatively high prevalence of pathological findings in the blood
      analysis and the orthopaedic examination can be attributed to the average age of
      the referees and none of them was performance limiting. CONCLUSIONS: Considering
      their risk of occult ischaemic heart disease, a precompetition medical assessment
      including an exercise ECG is recommended in elite male football referees.

PMID- 22144005
TI  - Hamstring muscle injuries in professional football: the correlation of MRI
      findings with return to play.
AB  - BACKGROUND: Hamstring injury is the single most common injury in professional
      football. MRI is commonly used to confirm the diagnosis and provide a prognosis
      of lay-off time. OBJECTIVE: To evaluate the use of MRI as a prognostic tool for
      lay-off after hamstring injuries in professional football players and to study
      the association between MRI findings and injury circumstances. METHODS:
      Prospective cohort study where 23 European professional teams, were followed
      between 2007 and 2011. Team medical staffs recorded individual player exposure
      and time-loss injuries. Radiological grading was performed using a modified
      Peetrons classification into four grades where grades 2 and 3 represent fibre
      disruption. RESULTS: In total, 516 hamstring injuries occurred and 58% of these
      were examined by MRI. Thirteen per cent were grade 0 injuries, 57% grade 1, 27%
      of grade 2 and 3% of grade 3. Grade 0 and 1 injuries accounted for 56% (2141/3830
      days) of the total lay-off. The lay-off time differed between all four
      radiological grades of injury (8+/-3, 17+/-10, 22+/-11 and 73+/-60 days,
      p<0.0001). Eighty-three per cent of injuries affected the biceps femoris while
      11% and 5% occurred to the semimembranosus and semitendinosus, respectively. Re
      injuries (N=34/207) constituted 16% of injuries. All re-injuries occurred to the
      biceps femoris. CONCLUSION: MRI can be helpful in verifying the diagnosis of a
      hamstring injury and to prognosticate lay-off time. Radiological grading is
      associated with lay-off times after injury. Seventy per cent of hamstring
      injuries seen in professional football are of radiological grade 0 or 1, meaning
      no signs of fibre disruption on MRI, but still cause the majority of absence
      days.

PMID- 22144006
TI  - Which domains of childhood physical activity predict physical activity in
      adulthood? A 20-year prospective tracking study.
AB  - PURPOSE: It is important to examine how childhood physical activity is related to
      adult physical activity in order to best tailor physical activity-promotion
      strategies. The time- and resource-intensive nature of studies spanning childhood
      into adulthood means the understanding of physical activity trajectories over
      this time span is limited. This study aimed to determine whether childhood domain
      specific physical activities predict domain-specific physical activity 20 years
      later in adulthood, and whether age and sex play a role in these trajectories.
      METHODS: In 1985, 6412 children of age 9-15 years self-reported frequency and
      duration of discretionary sport and exercise (leisure activity), transport
      activity, school sport and physical education (PE) in the past week and number of
      sports played in the past year. In 2004-2006, 2201 of these participants (aged 26
      36 years) completed the long International Physical Activity Questionnaire and/or
      wore a Yamax pedometer. Analyses included partial correlation coefficients and
      log-binomial regression. RESULTS: Childhood and adult activity were weakly
      correlated (r=-0.08-0.14). Total weekly physical activity in childhood did not
      predict adult activity. School PE predicted adult total weekly physical activity
      and daily steps (older females), while school sport demonstrated inconsistent
      associations. Leisure and transport activity in childhood predicted adult leisure
      activity among younger males and older females, respectively. Childhood past year
      sport participation positively predicted adult physical activity (younger males
      and older females). CONCLUSIONS: Despite modest associations between childhood
      and adult physical activity that varied by domain, age and sex, promoting a range
      of physical activities to children of all ages is warranted.

PMID- 22144007
TI  - The origin of tendon friction rubs in patients with systemic sclerosis: a
      sonographic explanation.

PMID- 22144008
TI  - Interactions of nanomaterials with the immune system.
AB  - Evaluation of the immunomodulatory potentials of nanomaterials is essential for
      developing safe and consumer-friendly nanotechnology. Various nanomaterials
      interact with the immune system, in a beneficial or deleterious way, but
      mechanistic details about such interactions are scarce. A lack of agreed-upon
      guidelines for evaluating the immunotoxicity of nanoparticles (NPs) adds to the
      complexity of the issue. Various review articles have summarized the immune
      system interactions of biodegradable NPs (with pharmaceutical uses), but such
      information is largely lacking for nonbiodegradable NPs. Here we give an overview
      of interactions of nonbiodegradable, persistent NPs with the immune system.
      Particular emphases include key factors that shape such interactions, cell
      specific responses, allergy and immune-sensitive respiratory disorders.

PMID- 22144009
TI  - Tuberculosis among children in Kenya: epidemiology and impact of HIV in two
      provinces.
AB  - We collected clinical register data on children in two provinces of Kenya and
      conducted bivariate and multivariate analyses to assess characteristics
      associated with death. Among 987 children with tuberculosis (TB), pulmonary
      disease was diagnosed in 689 (70%) children. Final outcomes were known for 830
      children, 40 (5%) of whom died during TB treatment. HIV test results were
      available for 670 (68%) children; 371 (55%) of whom tested positive. Only 63 of
      134 (47%) of children <1 year were tested for HIV. There were no data on CD4 or
      anti-retroviral use. The relative risk for death for HIV-infected children
      compared to HIV-uninfected children was 9.3 for children <1 year [95% confidence
      interval (CI) 1.2-69.2], 3.9 for children aged 1-4 (95% CI 0.9-17.7) and 0.9 for
      children aged 5-14 (95% CI 0.3-2.6). In Kenya, HIV infection in children with TB
      is common, and our data suggest that HIV is particularly deadly in TB patients <1
      year, the group with the lowest rate of testing. Poor data recording and
      reporting limit our understanding of TB in this age group. Expansion of HIV
      testing may improve survival, and more complete data recording and reporting will
      enhance our understanding of pediatric TB.

PMID- 22144010
TI  - Total antioxidant capacity and total oxidant status in perinatal asphyxia in
      relation to neurological outcome.
AB  - This study aimed to investigate the global oxidant/antioxidant status of infants
      with perinatal asphyxia and its relation to neurological outcomes. A prospective
      controlled study including term infants with perinatal asphyxia was conducted.
      Blood samples were obtained from patients and controls at 6-24 h and on the 3rd
      day of life for TAC and TOS measurement and OSI values were calculated.
      Neurodevelopment was evaluated at 12 months of age in survivors using Bayley
      scales of infant development II (BSID II). 17 term infants with perinatal
      asphyxia and 17 healthy controls were enrolled. On the first day of life TAC, TOS
      and OSI were significantly higher in patients with perinatal asphyxia (p<0.001).
      Total antioxidant capacity decreased significantly on day 3 compared to first day
      of life in the patient group (p=0.04). Infants with seizures and abnormal
      amplitude-integrated electroencephalography recordings had higher TOS and OSI
      levels in the 1st day. There was no correlation between TAC, TOS and OSI levels
      and BSID II scores. In conclusion oxidant/antioxidant balance is disturbed in
      favour of oxidants in perinatal asphyxia. Degree of oxidative stress is related
      to severity of neurological involvement in the first days of life.

PMID- 22144011
TI  - Long-term monitoring of a critically ill preterm infant with two-channel
      amplitude integrated electroencephalography.
AB  - Amplitude integrated electroencephalography (aEEG) is a user friendly technique
      suitable for long term continuous monitoring of cerebral electrical background
      activity. It is increasingly being used in monitoring high risk neonates in
      intensive care units. Newer two-channel aEEG monitors by providing data from both
      side of the brain may increase the sensitivity for detection of unilateral
      cerebral injury. Here we report a critically ill preterm neonate with
      intracranial hemorrhage who was monitored with the two-channel aEEG for 3 weeks
      continuously. Seizures were clearly detected by monitoring
      electroencephalographic activity of both hemispheres and efficacy of
      anticonvulsant therapy was evaluated objectively. Amplitude integrated EEG helps
      management of critically ill patients as it allows continuous long-term
      monitoring of brain functions.

PMID- 22144012
TI  - Cerebrospinal fluid IL-6, TNF-alpha and MCP-1 in children with acute
      lymphoblastic leukaemia during chemotherapy.
AB  - The aim of the study was to investigate the levels of cerebrospinal fluid (CSF)
      cytokines during chemotherapy of acute lymphoblastic leukaemia (ALL). Examination
      of 12 ALL child (6 boys and 6 girls) patients evidenced significant increases in
      interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) after induction
      treatment and significant increases in IL-6, tumour necrosis factor-alpha (TNF
      alpha) and MCP-1 levels during the consolidation phase, as compared to their
      values at the time of diagnosis. There were no significant differences in CSF IL
      6, TNF-alpha and MCP-1 concentrations after therapy. Our data suggest that
      standard ALL treatment may cause a subclinical inflammation and neurotoxicity.

PMID- 22144013
TI  - Ultrastructural characteristics and variability of vegetative reproduction in
      Fellomyces penicillatus.
AB  - The yeast strains VKM Y-2977 and VKM Y-2978, derived from the isolate Pa-202,
      were examined for their physiological properties and mycocin sensitivities and
      studied by light, phase-contrast, fluorescence, transmission and scanning
      electron microscopy. The cells of the first strain produced long stalk-like
      conidiophores, whereas the cells of the second one had the appearance of a
      typical budding yeast under the light microscope. Transmission and scanning
      electron microscopy showed the formation of stalk-like conidiophores and long
      necks in VKM Y-2977, similar in appearance to Fellomyces fuzhouensis. The actin
      cytoskeleton, microtubules and nuclei were similar as well, but due to presence
      of a capsule, they were not clearly visible. The second isolate, VKM Y-2978, had
      very short stalk-like conidiophores, and the neck, microtubules and actin cables
      were shorter as well. The actin patches, actin cables, and microtubules were
      similar in VKM Y-2977 and VKM Y-2978 and not clearly visible. The physiological
      characteristics and mycocin sensitivity patterns, together with the microscopic
      structures and ultrastructures, led us to conclude that both strains belong to
      Fellomyces penicillatus, even though they differ in the lengths of their stalk
      like conidiophores and necks.

PMID- 22144014
TI  - Mechanistic aspects and elementary steps of N-H bond activation of ammonia and C
      N coupling induced by gas-phase ions: a combined experimental/computational
      exercise.
AB  - In the last decades, N-H bond activation of ammonia and C-N coupling processes
      have formed the focus of broad research activities. More recently, gas-phase
      experiments combined with computational studies have provided rather detailed
      insights into the mechanisms and the elementary steps of these two reaction
      types. Some of the multifarious observations made and results obtained for these
      two processes mediated by gaseous "bare" or ligated ions are outlined in this
      review article.

PMID- 22144015
TI  - Determination of selenium in serum samples of preterm newborn infants with
      bronchopulmonary dysplasia using a validated hydride generation system.
AB  - Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is one of
      the most challenging complications in premature newborn infants. Selenium plays a
      role in antioxidant system by protecting cell membranes and neutralizing the
      deleterious effects of free radicals. The aim of this study was to determine the
      relationship between selenium concentration and incidence of bronchopulmonary
      dysplasia using a validated analytical method. Umbilical cord blood and blood
      samples 30 days after the birth were collected from 38 preterm newborn infants
      with gestation age of 32 weeks or less, and the separated serums were kept at -70
      degrees C until analysis time. Selenium concentration of serum was determined
      using an atomic absorption spectrophotometer. The method was validated on the
      basis of standard validation techniques. The analytical method was linear in the
      range of 1 to 500 MUg/L with the limit of detection of 0.4 MUg/L. Samples were
      collected from 38 infants whose gestation age was 32 weeks or less. The blood
      samples were collected from the umbilical cord blood at birth in 19 cases. In 25
      cases, blood samples were collected 1 month after birth. Of the 15 patients
      diagnosed with BPD, 10 were boys (p = 0.02). The mean serum selenium
      concentration was not different at birth between patients with and without BPD,
      but it was significantly lower at 30 days after birth in patients with BPD (38.5
      +/- 14.1vs. 45.4 +/- 18.7 MUg/L, p = 0.02). Preterm newborn infants with BPD had
      lower serum selenium concentrations 1 month after birth.

PMID- 22144016
TI  - Induction of cell cycle arrest and apoptosis by ruthenium complex cis
      (dichloro)tetramineruthenium(III) chloride in human lung carcinoma cells A549.
AB  - Lung cancer is one of the leading causes of death in the world, and non-small
      cell lung carcinoma (NSCLC) accounts for approximately 75-85% of all lung
      cancers. In the present work, we studied the cytotoxic activity, cell cycle
      arrest and induction apoptosis of the compound cis
      (dichloro)tetramineruthenium(III) chloride {cis-[RuCl(2)(NH(3))(4)]Cl} in human
      lung carcinoma tumor cell line A549. The results of MTT and trypan blue assays
      showed that cis-[RuCl(2)(NH(3))(4)]Cl causes reduction in the viability of A549
      cells when treating with 95 and 383 MUM of the compound for 48 and 72 h. Lower
      concentrations of the compound (19, 3.8 and 0.38 MUM), however, only slightly
      affected cell viability. The IC(50) value for the compound was about 383 MUM.
      Survival analysis of the A549 cells after treatment with ruthenium(III) compound
      using long term clonogenic assay showed that it reduced colony formation ability
      at concentrations of 0.38 and 3.8 MUM, and at concentrations of 95 and 383 MUM no
      colonies were observed. Cell cycle analysis showed that compound ruthenium led to
      an accumulation of A549 cells in S phase and increased in the sub-G1 peak. In
      addition, cis-(dichloro)tetramineruthenium(III) chloride treatment induced
      apoptosis, as observed by the increased numbers of annexin V-positive cells and
      increased messenger RNA expression of caspase-3.

PMID- 22144017
TI  - Whole blood selenium levels in healthy adults from the west of Algeria.
AB  - The purpose of this study was to assess whole blood selenium levels of 300
      healthy adults living in four selected areas of the west of Algeria. Selenium was
      measured using differential pulse cathodic stripping voltammetry with a detection
      limit of 29.20 MUg/L. The mean of whole blood selenium concentrations was 85.65
      +/- 21.60 MUg/L ranging between 30.90 and 144.04 MUg/L. This concentration did
      not vary significantly (P > 0.05) in relation to the gender of the subject, with
      concentrations of 87.75 +/- 21.30 MUg/L in men and 83.95 +/- 21.60 MUg/L in women
      group. Individuals older than 60 years had a whole blood selenium concentration
      significantly lower than the rest of the population. However, the measured
      selenium concentrations in the residential areas were not statistically different
      (P > 0.05). A total of 32 (10.70%) individuals exhibited whole blood selenium
      level below 60 MUg/L. These results are similar to those of some European
      countries but are much lower than data observed in USA or seleniferous regions.

PMID- 22144018
TI  - Modified natural clinoptilolite detoxifies small mammal's organism loaded with
      lead II: genetic, cell, and physiological effects.
AB  - The detoxification capacity of the clinoptilolite modification KLS-10-MA used as
      food additive in small mammals, chronically lead-exposed, was proven for the
      first time. The modified clinoptilolite was prepared based on natural Bulgarian
      clinoptilolite deposits. As a powder, it was mechanically mixed at 12.5%
      concentration with the conventional forage for small rodents. Lead in the form of
      aqueous solution of Pb(NO(3))(2) was diluted in the drinking water. In the
      ecotoxicological experiment covering 90 days, imprinting control region
      laboratory mice were used. They were allocated into four groups: group 1,
      (control): animals fed with conventional food for small rodents and water; group
      2: animals fed with conventional food + clinosorbent KLS-10-MA and water; group
      3: animals fed with conventional food and water + Pb(NO(3))(2); and group 4:
      animals fed with conventional food + KLS-10-MA and water + Pb(NO(3))(2). A group
      of non-exposed healthy animals was fed with conventional forage mixed with KLS-10
      MA to prove eventual toxicity of the sorbent and influence on growth performance.
      The changes in the chromosome structure, mitotic index, erythrocyte form,
      erythropoiesis, and body weight gain were recorded. On day 90, the following
      relations were established: Pb-exposed and clinoptilolite-supplemented mice
      exhibited 2.3-fold lower chromosome aberrations frequency, 2.5-fold higher
      mitotic index, and 1.5-fold higher percentage normal erythrocytes 1.3-fold higher
      body weight compared to Pb-exposed and unsupplemented animals. The obtained data
      showed that the sorbent is practically non-toxic. The results of the present
      study encourage a further elaboration of a reliable drug based on the tested
      substance in the cases of chronic lead intoxication.

PMID- 22144019
TI  - MRI of cells and mice at 1 and 7 Tesla with Gd-targeting agents: when the low
      field is better!
AB  - Tumor cells were targeted with Gd-loaded/LDL (low density lipoproteins) adducts
      consisting of ca 300 Gd(III) amphiphilic complexes incorporated in the lipophilic
      LDL particles. The long reorientational time of the Gd(III) complex in the
      supramolecular adduct yielded a relaxivity peak at ca 1 T, whereas its relaxivity
      at 7 T was 5 times less. The field-dependent relaxivity markedly affected the
      signal enhancement attainable at the two magnetic fields. As tumor cells showed
      up-regulation of LDL transporters, B16 melanoma cells were labeled with the Gd
      loaded/LDL adduct. Each cell contained ca 2 * 10(9) Gd atoms. Upon dispersion of
      5000 labeled cells in 1 MUl of agar, signal intensity (SI) enhancements of about
      30 and 7% were observed at 1 and 7 T, respectively. The results obtained on
      cellular systems were confirmed in vivo upon the administration of Gd-loaded/LDL
      particles to C57 mice bearing a transplanted melanoma (B16) tumor. From the
      herein reported results, one may conclude that, for slowly moving Gd complexes,
      it is possible to obtain in vivo sensitivity enhancements at 1 T several times
      higher than that attained at high fields.

PMID- 22144020
TI  - Dynamic manganese-enhanced magnetic resonance imaging can detect chronic
      cryoinjury-induced infarction in pig hearts in vivo.
AB  - The purpose was to investigate whether MnCl(2) can serve as an MRI contrast agent
      to detect chronic cryoinjury infarction in pigs in vivo and whether MnCl(2)
      causes significant hemodynamic disturbances. Hearts were subjected to a topical 2
      min cryothermia to establish myocardial infarction (MI). Thereafter GdDTPA
      enhanced MRI was performed at 0, 1, 2 and 3 weeks using a 3 T scanner. Four weeks
      post-cryoinjury the pigs underwent in vivo Mn-enhanced magnetic resonance imaging
      (MEMRI). MnCl(2) (70 MUmol/kg, 14 min) was infused i.v. intermittently (n = 4) or
      continuously (n = 5) and T(1)-weighted images were acquired every 2 min
      simultaneously recording heart rate and arterial blood pressure. Either infusion
      scheme led to an immediate increment in MR signal intensity (SI) within the left
      ventricular (LV) blood pool and LV normal and cryoinjured myocardium, which
      reached a maximum at the end of infusion. No significant difference was observed
      between the normal and cryoinjured myocardium. After infusion termination, SI
      decreased faster within the LV blood pool and the MI, as compared with the normal
      myocardium in either group, resulting in significant contrast between the MI and
      normal tissue (intermittent: 18 +/- 7 vs 49 +/- 13%, p = 0.002; continuous: 19 +/
      8 vs 36 +/- 9%, p = 0.004). Infarction sizes were similar in Mn(2+)- and GdDTPA
      enhanced images at 4 and 3 weeks post injury, respectively. Thus, in vivo MEMRI
      differentiated infarcted from normal myocardium in pig hearts subjected to 4-week
      cryoinjury. Compared with intermittent infusion, continuous infusion minimized
      hemodynamic fluctuations.

PMID- 22144021
TI  - Imaging efficiency of an X-ray contrast agent-incorporated polymeric
      microparticle.
AB  - Biocompatible polymeric encapsulants have been widely used as a delivery vehicle
      for a variety of drugs and imaging agents. In this study, X-ray contrast agent
      (iopamidol) is encapsulated into a polymeric microparticle (polyvinyl alcohol) as
      a particulate flow tracer in synchrotron X-ray imaging system. The physical
      properties of the designed microparticles are investigated and correlated with
      enhancement in the imaging efficiency by experimental observation and theoretical
      interpretation. The X-ray absorption ability of the designed microparticle is
      assessed by Beer-Lambert-Bouguer law. Particle size, either in dried state or in
      solvent, primarily dominates the X-ray absorption ability under the given
      condition, thus affecting imaging efficiency of the designed X-ray contrast flow
      tracers.

PMID- 22144022
TI  - A new optical imaging probe targeting alphaVbeta3 integrin in glioblastoma
      xenografts.
AB  - alpha(V)beta(3) Integrins are a widely recognized target for in vivo molecular
      imaging of pathological conditions such as inflammation, cancer and rheumatoid
      arthritis. We have evaluated the sensitivity of a new, near-infrared fluorescence
      (NIRF), RGD cyclic probe (DA364) in noninvasive detection of alpha(V) beta(3)
      integrin-overexpressing tumors. DA364's binding affinity for alpha(V)beta(3)
      integrin was first evaluated in vitro. Human alpha(V)beta(3) integrin-positive, U
      87 MG glioblastoma cells were then xenografted in nude mice, and DA364 was
      injected intravenously (i.v.) to evaluate its in vivo distribution, specificity
      and sensitivity in comparison with a commercially available probe. DA364 bound
      alpha(V)beta(3) integrin on U-87 MG cells with high affinity and specificity,
      both in vitro and in vivo. This binding specificity was corroborated by the
      strong inhibition of its tumor uptake induced by nonfluorescent, cyclic-RGD
      peptides. Ex vivo analysis showed that DA364 accumulated at the tumor site,
      whereas very low levels were detected in liver and spleen. In conclusion, DA364
      allows sensitive and specific detection of transplantable glioblastoma by NIRF
      imaging, and is thus a promising candidate for the elaboration of imaging and
      therapeutic probes for alpha(V)beta(3) integrin-overexpressing tumors.

PMID- 22144024
TI  - A novel foam fluid negative contrast medium for clear visualization of the colon
      wall in CT imaging.
AB  - Computed tomography (CT) imaging is a valuable tool for the diagnosis of
      colorectal diseases. However, the colonic wall depiction in 2D CT images is
      usually poor because of the low contrast between the colonic wall and the luminal
      content. In order to improve the visualization of the colonic wall and any
      abnormality on its surface, we report in this paper the development of an oil
      free foam fluid negative contrast medium for improved CT imaging of the colon.
      The foam fluid negative contrast medium was prepared by dispersing and
      stabilizing microbubbles in a polymeric solution. The stabilities of both the
      individual bubbles and the foam fluid system were optimized by incorporating
      bovine serum albumin and gluconolactone as the stabilization agent. The medium
      had a mean X-ray density of -120 Hounsfield units (close to that of the
      extraluminal tissues), and enabled clear 2D visualization of the colonic wall in
      both ex vivo and in vivo imaging studies. The measured colonic wall thicknesses
      at different segments in a beagle dog based on the 2D CT images obtained with the
      negative contrast medium accurately reflected the anatomical values, as compared
      with the values based on air-contrasted images. In vivo study of a simulated
      polyps pig model demonstrated sensitive detection of 11 out of 12 polyps with the
      smallest one 2 mm in diameter. We believe this new and safe foam fluid negative
      medium would enable the implementation of CT imaging as a convenient and useful
      tool for diagnosis of colon cancer, especially in the elderly population.

PMID- 22144023
TI  - The pH sensitivity of -NH exchange in LnDOTA-tetraamide complexes varies with
      amide substituent.
AB  - The amide proton exchange rates in various lanthanide(III) DOTA-tetraamide
      complexes were investigated by CEST as a function of variable chemical structures
      and charges on the amide substituents. Comparisons were made between YbDOTA
      (gly)(4)(-) (Yb-1), YbDOTA-(NHCH(2)PO(3))(4 (5-) (Yb-2) and YbDOTA
      (NHCH(2)PO(3)Et(2))(4)(3+) (Yb-3). The general shapes of the CEST vs pH profiles
      were similar for the three complexes but they showed maximum CEST intensities at
      different pH values, pH 8.3, 8.8 and 6.9 for Yb-1, Yb-2 and Yb-3, respectively.
      This indicates that a more negatively charged substituent on the amide helps
      stabilize the partial positive charge on the amide nitrogen and consequently more
      base is required to catalyze proton exchange. The chemical shifts of the -NH
      protons in Yb-1 and Yb-2 were similar (-17 ppm) while the -NH proton in Yb-3 was
      at -13 ppm. This shows that the crystal field produced by the amide oxygen donor
      atoms in Yb-3 is substantially weaker than that in the other two complexes. In an
      effort to expand the useful range of pH values that might be measured using these
      complexes as CEST agents, the shapes of the CEST vs pH curves were also
      determined for two thulium(III) complexes with much larger hyperfine shifted -NH
      proton resonances. The ratio of CEST from -NH exchange in Tm-1 compared with CEST
      from -NH exchange in Tm-3 was found to be linear over an extended pH range, from
      6.3 to 7.4. This demonstrates a potential advantage of using mixtures of
      lanthanide(III) DOTA-tetraamides for mapping tissue pH by use of ratiometric CEST
      imaging.

PMID- 22144026
TI  - The Gd3+ complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      mono(p-isothiocyanatoanilide) conjugated to inulin: a potential stable
      macromolecular contrast agent for MRI.
AB  - Reaction of DOTA-NCSA [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      mono(p-isothiocyanatoanilide)] with O-(aminopropyl)inulin (degree of
      polymerization 25) provided a chelate that formed a kinetically extremely stable
      Gd(3+) complex. No transmetalation was observed with Zn(2+). The conjugate has a
      relaxivity of 21.7 s(-1) mM(-1) at 20 MHz and 37  degrees C, and each molecule of
      the inulin carries on average 35 Gd(3+) ions. The parameters governing the
      relaxivity of this material and of a low-molecular-weight model compound prepared
      by conjugation of DOTA-NCSA and propylamine were evaluated by investigation of
      their water (1)H longitudinal relaxation rate enhancements at different magnetic
      fields (NMRD) and by studying variable temperature (17)O NMR data. The high
      relaxivity of the inulin conjugate can be ascribed to the efficient slowing down
      of the molecular tumbling by this carrier. The rotational correlation time at 37 
      degrees C of this material is 1460 ps, whereas that of the model compound is 84
      ps. Furthermore, both complexes do not interact significantly with human serum
      albumin, as shown by their NMRD profiles, and do not undergo transmetallation by
      zinc ions. The inulin conjugate thus has potential for application as a contrast
      agent for MRI, particularly as a blood pool agent.

PMID- 22144025
TI  - beta-Cell subcellular localization of glucose-stimulated Mn uptake by X-ray
      fluorescence microscopy: implications for pancreatic MRI.
AB  - Manganese (Mn) is a calcium (Ca) analog that has long been used as a magnetic
      resonance imaging (MRI) contrast agent for investigating cardiac tissue
      functionality, for brain mapping and for neuronal tract tracing studies.
      Recently, we have extended its use to investigate pancreatic beta-cells and
      showed that, in the presence of MnCl(2), glucose-activated pancreatic islets
      yield significant signal enhancement in T(1)-weigheted MR images. In this study,
      we exploited for the first time the unique capabilities of X-ray fluorescence
      microscopy (XFM) to both visualize and quantify the metal in pancreatic beta
      cells at cellular and subcellular levels. MIN-6 insulinoma cells grown in
      standard tissue culture conditions had only a trace amount of Mn, 1.14 +/- 0.03 *
      10(-11)ug/um(2), homogenously distributed across the cell. Exposure to 2 mM
      glucose and 50 uM MnCl(2) for 20 min resulted in nonglucose-dependent Mn uptake
      and the overall cell concentration increased to 8.99 +/- 2.69 * 10(-11) ug/um(2).
      When cells were activated by incubation in 16 mM glucose in the presence of 50 uM
      MnCl(2), a significant increase in cytoplasmic Mn was measured, reaching 2.57 +/-
      1.34 * 10(-10) ug/um(2). A further rise in intracellular concentration was
      measured following KCl-induced depolarization, with concentrations totaling 1.25
      +/- 0.33 * 10(-9) and 4.02 +/- 0.71 * 10(-10) ug/um(2) in the cytoplasm and
      nuclei, respectively. In both activated conditions Mn was prevalent in the
      cytoplasm and localized primarily in a perinuclear region, possibly corresponding
      to the Golgi apparatus and involving the secretory pathway. These data are
      consistent with our previous MRI findings, confirming that Mn can be used as a
      functional imaging reporter of pancreatic beta-cell activation and also provide a
      basis for understanding how subcellular localization of Mn will impact MRI
      contrast.

PMID- 22144027
TI  - A methodical 68Ga-labelling study of DO2A-(butyl-L-tyrosine)2 with cation
      exchanger post-processed 68Ga: practical aspects of radiolabelling.
AB  - Positron emission tomography (PET) with (68)Ga is a fast-growing field in
      molecular imaging, both in research and in clinical routine. The availability of
      (68)Ga via the (68)Ge/(68)Ga radionuclide generator facilitates the development
      and production of radiopharmaceuticals independent of a cyclotron. The presented
      work shows a complete (68) Ga labelling study exemplified on [(68)Ga]DO2A-(butyl
      L-tyrosine)(2), a potential tumour tracer for PET. A methodical sequence is
      followed to optimize the (68)Ga-labelling reaction. Practical aspects are
      described and the different parameters contributing to the labelling yield are
      demonstrated. The influence of temperature, time, amount of labelling precursor
      and pH value on the radiochemical yields is demonstrated. A conventional heating
      method is compared with microwave irradiation as an alternative labelling method.
      Finally, purification of (68)Ga-labelled compounds via solid-phase extraction and
      quality control is shown. The procedure described in this manuscript may serve as
      a guideline for optimizing (68)Ga labelling reactions.

PMID- 22144028
TI  - Deuteration of a molecular probe for DNP hyperpolarization--a new approach and
      validation for choline chloride.
AB  - The promising dynamic nuclear polarization (DNP) for hyperpolarized (13)C-MRI/MRS
      of real-time metabolism in vivo is challenged by the limited number of agents
      with the required physical and biological properties. The physical requirement of
      a liquid-state T(1) of tens of seconds is mostly found for (13)C-carbons in small
      molecules that have no direct protons attached, i.e. carbonyl, carboxyl and
      certain quaternary carbons. Unfortunately, such carbon positions do not exist in
      a large number of metabolic agents, and chemical shift dispersion often limits
      detection of their chemical evolution. We have previously shown that direct
      deuteration of protonated carbon positions significantly prolongs the (13)C T(1)
      in the liquid state and provides potential (13)C-labeled agents with differential
      chemical shift with respect to metabolism. The Choline Molecular Probe [1,1,2,2
      D(4), 2-(13)C]choline chloride (CMP2) has recently been introduced as a means of
      studying choline metabolism in a hyperpolarized state. Here, the biophysical
      properties of CMP2 were characterized and compared with those of [1
      (13)C]pyruvate to evaluate the impact of molecular probe deuteration. The CMP2
      solid-state polarization build-up time constant (30 min) and polarization level
      (24%) were comparable to those of [1-(13)C]pyruvate. Both compounds' liquid state
      T(1) increased with temperature. The high-field T(1) of CMP2 compared favorably
      with [1-(13)C]pyruvate. Thus, a deuterated agent demonstrated physical properties
      comparable to a hyperpolarized compound of already proven value, whereas both
      showed chemical shift dispersion that allowed monitoring of their metabolism. It
      is expected that the use of deuterated carbon-13 positions as reporting
      hyperpolarized nuclei will substantially expand the library of agents for DNP-MR.

PMID- 22144029
TI  - The presence of iodinated contrast agents amplifies DNA radiation damage in
      computed tomography.
AB  - The purpose of this study was to determine the influence of iodinated contrast
      agents on the formation of DNA double-strand breaks in vitro in lymphocytes and
      to verify these results in patients undergoing diagnostic computed tomography
      examinations. Blood samples were irradiated in vitro in the presence of iodinated
      X-ray contrast agent. Controls were irradiated without contrast agent. Fourteen
      patients were investigated using contrast-enhanced computed tomography (CT), and
      14 other patients with unenhanced CT. Blood samples were taken prior to and 5 min
      and 1, 2 and 24 h after the CT examination. In these blood samples the average
      number of gammaH2Ax-foci per lymphocyte was enumerated by fluorescence
      microscopy. Statistical differences between foci numbers developed in the
      presence and absence of contrast agent were tested using an independent sample t
      test. In vitro foci numbers after irradiation were significantly higher when
      contrast agent was present during irradiation. In vivo, gammaH2Ax-foci levels
      were 58% higher in patients undergoing contrast-enhanced CT compared with those
      undergoing unenhanced CT. In the presence of iodinated contrast agents DNA,
      damage is increased and the radiation dose is not the only factor affecting the
      amount of DNA damage. Individual patient characteristics and biological dosimetry
      applications, e.g. the analysis of gammaH2Ax-foci, have to be considered.

PMID- 22144030
TI  - Labeling of multiple cell lines using a new iron oxide agent for cell tracking by
      MRI.
AB  - Stem cells, cancer cells and immune cells were labeled by co-incubation with a
      new ultra-small iron oxide nanoparticle called Molday ION Rhodamine-B (MIRB).
      Iron staining, fluorescence imaging, transmission electron microscopy and flow
      cytometry were used to assess cell viability, function and labeling efficiency.
      This study has shown that MIRB can be used to label both adherent and nonadherent
      cell lines, with high viability and loading levels sufficient for their detection
      in vivo by MRI at 3 T.

PMID- 22144032
TI  - Physical changes and physiological characteristics of red and green peel during
      nectarine (cv. Hu018) maturation.
AB  - BACKGROUND: The aim of this study was to determine physical changes in nectarine
      and distinctive physiological characteristics related to red and green peel under
      stresses occurring during fruit maturation, information on which is currently not
      available. RESULTS: Fruit firmness increased from 4 to 6 weeks after blooming
      (WAB) then decreased from 6 WAB until ripening. Anthocyanins in red and green
      peel during nectarine maturation were identified by high-performance liquid
      chromatography as cyanidin 3-glucoside together and, at a much lower level,
      cyanidin 3-rutinoside. Cyanidins in red and green peel decreased from 4 to 8 WAB
      then increased from 8 to 12 WAB. Anthocyanin contents were positively correlated
      with PAL, POD, A*, MDA and O2(.-) values and inversely correlated with L* and B*
      values. Red and green peel during maturation could be separated by hierarchical
      cluster analysis of the tested data. CONCLUSION: This study has provided an
      overview of red and green peel characteristics during nectarine (cv. Hu018)
      maturation. Values of A*, anthocyanins, O2(.-), MDA, PAL, PPO and POD in red peel
      were higher than those in green peel, while values of L*, B* and chroma in red
      peel were lower than those in green peel throughout fruit maturation.

PMID- 22144033
TI  - QT prolongation of the antipsychotic risperidone is predominantly related to its
      9-hydroxy metabolite paliperidone.
AB  - OBJECTIVE: A dose-dependent increase in risk of sudden cardiac death for the
      antipsychotic drug risperidone was reported. However, few reports have so far
      addressed QT prolongation associated with the use of risperidone or its major
      active metabolite, which is also used as a separate antipsychotic drug,
      paliperidone. METHODS: The present study evaluated associations between
      risperidone metabolism and QT interval in 61 psychiatric patients who had been
      receiving risperidone for >=4 weeks at an average dosage of 4.7 mg/day. Plasma
      risperidone and paliperidone levels were measured and electrocardiographic
      measurements were also obtained. RESULTS: There was no correlation between
      risperidone dosage and QTc or plasma risperidone levels and QTc. However, there
      was a significant positive correlation between plasma paliperidone levels and QTc
      (r = 0.361; p = 0.004). There was no correlation between age and dose-corrected
      plasma risperidone levels or between age and QTc. There was a significant
      positive correlation between age and dose-corrected plasma paliperidone levels (r
      = 0.290; p = 0.023). CONCLUSION: Clinically, paliperidone is considered to play a
      more important role in QT prolongation than risperidone.

PMID- 22144034
TI  - Risk of cancer in patients exposed to gabapentin in two electronic medical record
      systems.
AB  - PURPOSE: High doses of gabapentin were associated with pancreatic acinar cell
      tumors in male Wistar rats, but there is little published epidemiological data
      regarding gabapentin and carcinogenicity. We explored the association between
      gabapentin and cancer in a US medical care program and followed up nominally
      significant associations in a UK primary care database. METHODS: In the US Kaiser
      Permanente Northern California (KPNC) health system, we performed nested case
      control analyses of gabapentin and 55 cancer sites and all cancers combined using
      conditional logistic regression. Up to 10 controls were matched to each case on
      year of birth, sex, and year of cohort entry. No other covariates were included
      in models. Only dispensings for gabapentin 2 years or more before index date were
      considered. Nominally significant associations with an OR > 1.00 and p < 0.05 for
      three or more dispensings versus no dispensings were followed up by similar
      nested case-control analyses in the UK General Practice Research Database (GPRD),
      adjusting for potential indications for gabapentin and risk factors for the
      specific cancers. RESULTS: The following analyses had OR > 1.00 and p < 0.05 for
      three or more dispensings of gabapentin versus no dispensing (2-year lag) in KPNC
      and were also examined in the GPRD: all cancers, breast, lung and bronchus,
      urinary bladder, kidney/renal pelvis, stomach, anus/anal canal/anorectum, penis,
      and other nervous system. These cancers were not statistically significantly
      associated with gabapentin in the GPRD case-control studies (2-year lag). The
      GPRD and KPNC studies did not identify a statistically significant increased risk
      of pancreatic cancer with more than two prescriptions of gabapentin in the 2-year
      lagged analyses. CONCLUSIONS: The epidemiological data in a US cohort with up to
      12 years of follow-up and a UK cohort with up to 15 years of follow-up do not
      support a carcinogenic effect of gabapentin use. However, the confidence
      intervals for some analyses were wide, and an important effect cannot be
      confidently excluded.

PMID- 22144035
TI  - Decreased Th17 and antigen-specific humoral responses in CX3 CR1-deficient mice
      in the collagen-induced arthritis model.
AB  - OBJECTIVE: CX(3) CR1 is a chemokine receptor that uniquely binds to its ligand
      fractalkine (CX(3) CL1) and has been shown to be important in inflammatory
      arthritis responses, largely due to its effects on cellular migration. This study
      was undertaken to test the hypothesis that genetic deficiency of CX(3) CR1 is
      protective in the chronic inflammatory arthritis model collagen-induced arthritis
      (CIA). Because CX(3) CR1 is expressed on T cells and antigen-presenting cells, we
      also examined adaptive immune functions in this model. METHODS: Autoantibody
      formation, clinical, histologic, T cell proliferative, and cytokine responses
      were evaluated in wild-type and CX(3) CR1-deficient DBA/1J mice after
      immunization with heterologous type II collagen (CII). RESULTS: CX(3) CR1(-/-) 
      mice had an ~30% reduction in arthritis severity compared to wild-type mice, as
      determined by 2 independent measures, paw swelling (P < 0.01) and clinical
      disease score (P < 0.0001). Additionally, compared to wild-type mice, CX(3) CR1(
      /-)  mice had an ~50% decrease in anti-CII autoantibody formation (P < 0.05),
      decreased Th17 intraarticular cytokine expression (P < 0.01 for interleukin-17
      [IL-17] and P < 0.001 for IL-23), and decreased total numbers of Th17 cells in
      inflamed joints (P < 0.05). CONCLUSION: Our findings indicate that CX(3) CR1
      deficiency is protective in inflammatory arthritis and may have effects that
      extend beyond migration that involve adaptive immune responses in autoimmune
      disease.

PMID- 22144036
TI  - Hydrogels and microtechnologies for engineering the cellular microenvironment.
AB  - Hydrogels represent a class of materials suitable for numerous biomedical
      applications such as tissue engineering and drug delivery. Hydrogels are by
      definition capable of absorbing large amount of fluid, making them adequate for
      cell seeding and encapsulation as well as for implantation because of their
      biocompatibility and excellent diffusion properties. They also possess other
      desirable properties for fundamental research as they have the ability to mimic
      the basic three-dimensional (3D) biological, chemical, and mechanical properties
      of native tissues. Furthermore, their biological interactions with cells can be
      modified through the numerous side groups of the polymeric chains. Thus, the
      biological, chemical, and mechanical properties, as well as the degradation
      kinetics of hydrogels can be tailored depending on the application. In addition,
      their fabrication process can be combined with microtechnologies to enable
      precise control of cell-scale features such as surface topography and the
      presence of adhesion motifs on the hydrogel material. This ability to control the
      microscale structure of hydrogels has been used to engineer tissue models and to
      study cell behavior mechanisms in vitro. New approaches such as bottom-up and
      directed assembly of microscale hydrogels (microgels) are currently emerging as
      powerful methods to enable the fabrication of 3D constructs replicating the
      microenvironment found in vivo.

PMID- 22144038
TI  - [Comments of the DGP on the press release dated 21.10. 2011 of the National
      Heart, Lung and Blood Institute about the PANTHER Study on IPF patients].

PMID- 22144039
TI  - Diagnosis of peripheral lung lesions by EBUS-guided TBB in routine practice.
AB  - OBJECTIVE: To determine the diagnostic yield of EBUS guided TBB performed in
      routine practice with flexible bronchoscopy and under moderate sedation in
      ambulatory and hospitalized patients. METHODS: Bronchoscopy was performed under
      standard conditions in ambulatory and hospitalised patients. Bronchoscopically
      invisible peripheral pulmonary lesions were located with 20 MHZ-EBUS-probe and
      transbronchial biopsy was taken using a guiding sheath. Fluoroscopy was
      additionally performed as required to identify the lesion. RESULTS: 257 patients
      with peripheral pulmonal lesions were investigated, with malignancy in 70% of
      those with a diagnosis established. 175/257 (68.1%) of lesions were detected with
      EBUS. In 139/176 (79.4%) of these lesions, TBB enabled a final diagnosis. The TBB
      yield depended on lesion size. It was 61.3% in lesions <=20 mm, 85.5% >20 mm/<=30
      mm, and 81.2% in >=30 mm (p<0.0001). This yield was also affected by the position
      of the probe (centrally 84.5%, tangentially 57.6%, p=0.01)). Operator experience
      did not influence the diagnostic yield but considerably shortened investigation
      time (4.9+/-3.5 vs. 6.2+/-4.2 min, p=0.042). Relevant complications occurred in
      only 1.9% (3 cases of postinterventional pneumothorax). CONCLUSIONS: In an
      unselected population, EBUS-guided TBB has a high diagnostic yield in peripheral
      lesions >20 mm whereas its yield decreases considerably in smaller lesions.
      Complications are very rare. EBUS-guided TBB can successfully and safely be
      performed by flexible bronchoscopy.

PMID- 22144040
TI  - One-pot aqueous solution syntheses of iron oxide nanostructures with controlled
      crystal phases through a microbial-mineralization-inspired approach.
AB  - Iron-oxidizing bacteria produce trivalent iron oxides with the controlled crystal
      phases outside of their cells. Herein we have synthesized iron oxides with
      controlled oxidation states and crystal phases through a microbial-mineralization
      inspired approach in an aqueous solution at low temperature. Trivalent iron
      oxides, such as lepidocrocite, ferrihydrite, goethite, and hematite, are
      selectively obtained from an aqueous solution containing divalent iron ions below
      90  degrees C. The presence of a chelating agent facilitates the control of the
      oxidation states through the ligand-controlled approach because the precipitation
      of the divalent iron species is inhibited by the complexation between divalent
      iron ion and a chelating agent. The control of the crystal phases is achieved by
      the tuning of the synthetic conditions, such as the initial pH, the concentration
      of a chelating agent, and the reaction temperature. Furthermore, the resultant
      iron oxides have hierarchically organized structures consisting of nanoscale
      objects. The microbial-mineralization-inspired approach by using a chelating
      agent has potentials for the further morphological control of iron oxides and the
      further application to aqueous-solution syntheses of other metal oxides.

PMID- 22144041
TI  - Abstracts of the 10th International Symposium on VIP-PACAP and Related Peptides.
      December 13-16, 2011. Eilat, Israel.

PMID- 22144042
TI  - A novel technique to collect root exudates from mustard (Brassica juncea).
AB  - A very simple, novel, cost effective, easy to use technique has been developed
      for the collection of root exudates from small seeded plants, under laboratory
      conditions. 200-1000 MUl micro tips (Tarsons), kept in 100 ml glass beakers, were
      used as holders for the small seeds of Indian mustard (Brassica juncea) and the
      exudates were trapped in liquid culture medium. The exudates, so obtained, were
      authenticated and analyzed for organic compounds such as sugars, amino acids and
      organic acids, as well as chemotactic response towards rhizobacteria. Method was
      found to be suitable and easy to handle for small seeds.

PMID- 22144043
TI  - Rice varieties in relation to rice bread quality.
AB  - BACKGROUND: It is difficult to predict rice bread quality only from the amylose
      content (AC) or dough characteristics of new lines produced by rice breeding
      programmes. This study investigated the AC relative to bread baking quality of
      rice varieties developed in Korea, and identified specific characteristics that
      contribute to rice bread quality. RESULTS: Manmibyeo, Jinsumi, Seolgaeng and
      Hanareumbyeo were classified as low AC, YR24088 Acp9, Suweon517, Chenmaai and
      Goamibyeo as intermediate AC and Milyang261 as high AC. Suweon517, Milyang261 and
      Manmibyeo had a high water absorption index (WAI), while Goamibyeo, YR24088 Acp9,
      Jinsumi, Seolgaeng, Hanareumbyeo and Chenmaai had a low WAI. The gelatinisation
      enthalpy of flour varied from 9.2 J g(-1) in Milyang261 to 14.8 J g(-1) in
      YR24088 Acp9. After 7 days of storage the rate of flour retrogradation and crumb
      firmness were weakly correlated, with the exception of Jinsumi. Bread volumes of
      Jinsumi, Chenmaai, YR24088 Acp9 and Goamibyeo were comparable to that of wheat
      flour, but the rest were unsuited to bread making because of their low volume and
      hard crumb texture. CONCLUSION: Based on volume, texture and crumb firmness
      ratio, Chenmaai and Goamibyeo were the most appropriate varieties for making
      bread. An intermediate AC and low WAI were the primary indicators of rice bread
      flour quality.

PMID- 22144044
TI  - Postprandial inflammatory response in adipose tissue of patients with metabolic
      syndrome after the intake of different dietary models.
AB  - SCOPE: Dysfunctional adipose tissue may be an important trigger of molecular
      inflammatory pathways that cause cardiovascular diseases. Our aim was to
      determine whether the specific quality and quantity of dietary fat produce
      differential postprandial inflammatory responses in adipose tissue from metabolic
      syndrome (MetS) patients. METHODS AND RESULTS: A randomized, controlled trial
      conducted within the LIPGENE study assigned MetS patients to 1 of 4 diets: (i)
      high-saturated fatty acid (HSFA), (ii) high-monounsaturated fatty acid (HMUFA),
      (iii) low-fat, high-complex carbohydrate diet supplemented with n-3
      polyunsaturated fatty acids (PUFA) (LFHCC n-3), and (iv) low-fat, high-complex
      carbohydrate diet supplemented with placebo (LFHCC), for 12 wk each. A fat
      challenge reflecting the fatty acid composition as the original diets was
      conducted post-intervention. We found that p65 gene expression is induced in
      adipose tissue (p=0.003) at the postprandial state. In addition, IkappaBalpha
      (p<0.001), MCP-1 (p<0.001) and IL-1beta (p<0.001) gene expression was equally
      induced in the postprandial state, regardless of the quality and quantity of the
      dietary fat. Notably, IL-6 transcripts were only detected in the postprandial
      state. CONCLUSIONS: Our results indicate that individuals with MetS typically
      exhibit exacerbated adipose tissue postprandial inflammatory responses, which
      seem to be independent of the quality and quantity of dietary fat.

PMID- 22144046
TI  - The effect of group instrumental reminiscence therapy in older single veterans
      who live in a veterans home in Taiwan.

PMID- 22144045
TI  - Vascular deconjugation of quercetin glucuronide: the flavonoid paradox revealed?
AB  - SCOPE: The dietary flavonoid quercetin exerts protective cardiovascular effects.
      Because quercetin is rapidly metabolized into less active or inactive
      glucuronidated metabolites and the plasma concentrations of free quercetin are
      very low, a huge amount of scientific data generated along decades with the
      unconjugated compounds in vitro has been questioned. We aimed to determine
      whether glucuronidated quercetin can deconjugate in situ and whether
      deconjugation leads to a biological effect. METHODS AND RESULTS: Quercetin and
      quercetin-3-O-glucuronide (Q3GA) were perfused through the isolated rat
      mesenteric vascular bed. Quercetin was rapidly metabolized in the mesentery. In
      contrast, the decay of Q3GA was slower and was accompanied by a progressive
      increase of quercetin in the perfusate and in the tissue over 6 h, which was
      prevented by the beta-glucuronidase inhibitor saccharolactone. Incubation of
      mesenteric arterial rings mounted in a wire myograph with Q3GA for >=1 h resulted
      in a significant inhibition of the contractile response which was also prevented
      by saccharolactone. Moreover, the intravenous administration of Q3GA resulted in
      a slow onset and sustained blood pressure lowering effect, demonstrating for the
      first time that Q3GA has effects in vivo. CONCLUSION: We propose that Q3GA
      behaves as a quercetin carrier in plasma, which deconjugates in situ releasing
      the aglycone which is the final effector.

PMID- 22144047
TI  - A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase
      (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer
      patients treated with thoracic radiation therapy.
AB  - BACKGROUND: This study examined the association between functional single
      nucleotide polymorphisms in candidate genes from oxidative stress pathways and
      risk of radiation pneumonitis (RP) in patients treated with thoracic radiation
      therapy for locally advanced lung cancer. METHODS: A review was conducted of 136
      patients treated with radiation therapy for lung cancer between 2001 and 2007,
      and who had prior genotyping of functional single-nucleotide polymorphisms in
      oxidative stress genes including superoxide dismutase 2 (SOD2; rs4880) and
      methylene tetrahydrofolate reductase (MTHFR; rs1801131, rs1801133). RP events
      were retrospectively scored using the National Cancer Institute Common
      Terminology Criteria for Adverse Events, version 4.0. Cox proportional hazard
      regression was performed to identify clinical variables and genotypes associated
      with risk of RP of grades >=2 and >=3 on univariate and multivariate analysis,
      respectively. P values were corrected for multiple hypothesis esting. RESULTS:
      With a median follow-up of 21.4 months, the incidence of grade >=2 RP was 29% and
      grade >=3 RP was 14%. On multivariate analysis, after adjusting for clinical
      factors such as concurrent chemotherapy and consolidation docetaxel, and lung
      dosimetric parameters such as volume receiving greater than 20 Gy and mean lung
      dose, MTHFR genotype (rs1801131; AA versus AC/CC) was significantly associated
      with risk of grade >=2 RP (hazard ratio: 0.37; 95% confidence interval: 0.18
      0.76; P = .006, corrected P = .018) and grade >=3 RP (hazard ratio: 0.21; 95%
      confidence interval: 0.06-0.70; P = .01; corrected P = .03). SOD2 genotype was
      not associated with RP. CONCLUSIONS: This study showed an association between
      MTHFR genotype and risk of clinically significant RP. Further study of MTHFR
      related pathways may provide insight into the mechanisms behind RP.

PMID- 22144048
TI  - On the cardinal measurement of health inequality when only ordinal information is
      available on individual health status.
AB  - This paper suggests new indices of health inequality which may be used when only
      ordinal information is available on individual health status. We borrow ideas
      from the literature on the measurement of occupational or residential segregation
      and show that indices of ordinal segregation which have been recently proposed
      may be also applied to the measurement of health inequality. We also prove that
      these indices satisfy four axioms introduced to measure inequality with ordered
      response health data so that the new indices presented in this paper are
      consistent with the inequality ordering proposed by Allison and Foster. We also
      suggest an extension of the family of indices proposed by Abul Naga and Yalcin.

PMID- 22144049
TI  - Intriguing role of a quaternary ammonium cation in the dissociation chemistry of
      Keggin polyoxometalate anions.
AB  - The gas-phase fragmentations of a series of Keggin polyoxometalate anions with
      molecular formula of TBA(n)[XM(12)O(40)] (X = P, Si; M = Mo, W) were studied by
      electrospray ionization tandem mass spectrometry. The bare polyoxoanions
      [XM(12)O(40)](n-) as well as the non-covalent complexes {TBA[XM(12)O(40)]}((n-1)
      ) and {TBA(m)[XM(12)O(40)](2)}(3-) displayed characteristic dissociation
      pathways. Fragmentation of [XM(12)O(40)](n-) led to pairs of complementary
      product anions whose total stoichiometry and charge matched those of the
      precursor anion, consistent with the previous study by Ma et al. The nature of
      the non-covalent interaction between [XM(12)O(40)](n-) and TBA(+) was addressed
      in detail via the example of {TBA[XM(12)O(40)]}((n-1)-). The non-covalent
      interaction [1] primarily dominated by the Coulombic attraction of the opposite
      charges completely changed the dissociation chemistry of [XM(12)O(40)](n-). The
      non-covalent complexes {TBA[XM(12)O(40)]}((n-1)-) and {TBA(m)[XM(12)O(40)](2)}(3
      ), formed by the charge reduction during the electrospray process, underwent
      distinct dissociation routes: {TBA[XM(12)O(40)]}((n-1)-) fragmented to give rise
      to its product ion {(C(4)H(9))[XM(12)O(40)]}((n-1)-) by cleaving the N-C covalent
      bond inside the TBA(+) cation whereas {TBA(m)[XM(12)O(40)](2)}(3-) dissociated
      into a pair of product ions, {TBA(i)[XM(12)O(40)]}(2-) and {TBA(m
      i)[XM(12)O(40)]}(-), by breaking the non-covalent bond between [XM(12)O(40)](n-)
      and TBA(+). In addition, energy-variable CID was used to map the relative
      stabilities of the ion clusters in the gas phase, which was in excellent
      agreement with the relative orders of thermal stability in the condensed phase.

PMID- 22144050
TI  - Early postoperative care following endoscopic sinus surgery: an evidence-based
      review with recommendations.
AB  - BACKGROUND: Early postoperative care following endoscopic sinus surgery (ESS) has
      been suggested to minimize avoidable complications and optimize long-term
      outcomes. Several postoperative care strategies have been proposed but a formal
      comprehensive evaluation of the evidence has never been performed. The purpose of
      this article is to provide an evidence-based approach to early postoperative care
      following ESS. METHODS: A systematic review of the literature was performed and
      the Clinical Practice Guideline Manual, Conference on Guideline Standardization
      (COGS), and the Appraisal of Guidelines and Research Evaluation (AGREE)
      instrument recommendations were followed. Study inclusion criteria were: adult
      population >18 years old; chronic rhinosinusitis (CRS) based on published
      diagnostic criteria; ESS following failed medical therapy; primary study
      objective was to evaluate an ESS early postoperative care strategy; and clearly
      defined primary clinical end-point. RESULTS: This review identified and evaluated
      the literature on 7 early postoperative care strategies following ESS: saline
      irrigations, sinus cavity debridements, systemic steroids, topical steroids, oral
      antibiotics, topical decongestants, and drug-eluting spacers/stents. CONCLUSION:
      Based on the available evidence, use of nasal saline irrigation, sinus cavity
      debridement, and standard topical nasal steroid spray are recommended early
      postoperative care interventions. Postoperative antibiotic, systemic steroid,
      nonstandard topical nasal steroid solution, and/or drug-eluting spacers/stents
      are options in postoperative management. These evidence-based recommendations
      should not necessarily be applied to all postoperative patients and clinical
      judgment, in addition to evidence, is critical to determining the most
      appropriate care.

PMID- 22144051
TI  - Development of an evidence-based review with recommendations using an online
      iterative process.
AB  - BACKGROUND: The practice of modern medicine is governed by evidence-based
      principles. Due to the plethora of medical literature, clinicians often rely on
      systematic reviews and clinical guidelines to summarize the evidence and provide
      best practices. Implementation of an evidence-based clinical approach can
      minimize variation in health care delivery and optimize the quality of patient
      care. METHODS: This article reports a method for developing an "Evidence-based
      Review with Recommendations" using an online iterative process. The manuscript
      describes the following steps involved in this process: Clinical topic selection,
      Evidence-hased review assignment, Literature review and initial manuscript
      preparation, Iterative review process with author selection, and Manuscript
      finalization. RESULTS: The goal of this article is to improve efficiency and
      increase the production of evidence-based reviews while maintaining the high
      quality and transparency associated with the rigorous methodology utilized for
      clinical guideline development. CONCLUSION: With the rise of evidence-based
      medicine, most medical and surgical specialties have an abundance of clinical
      topics which would benefit from a formal evidence-based review. Although clinical
      guideline development is an important methodology, the associated challenges
      limit development to only the absolute highest priority clinical topics. As
      outlined in this article, the online iterative approach to the development of an
      Evidence-based Review with Recommendations may improve productivity without
      compromising the quality associated with formal guideline development
      methodology.

PMID- 22144052
TI  - The effects of nitric oxide on Staphylococcus aureus biofilm growth and its
      implications in chronic rhinosinusitis.
AB  - BACKGROUND: The relationship between sinonasal nitric oxide (NO) levels and the
      pathogenic organism Staphylococcus aureus is yet to be established. High NO
      levels measured in healthy sinuses likely contribute to maintenance of relative
      sterility. Lower concentrations such as is found in the sinuses of chronic
      rhinosinusitis (CRS) patients may decrease this effect. S. aureus in biofilm form
      has recently been implicated in recalcitrant CRS, its isolation predicting a
      higher risk of posttreatment reinfection. This in vitro study aims to
      characterize the changes in S. aureus biofilm formation when exposed to different
      NO levels mimicking the normal and diseased NO sinus concentrations reported in
      previous literature in an in vitro setting. METHODS: S. aureus ATCC 25923 and 7
      clinical isolates were cultured in biofilm form using the MBEC device and the
      established biofilms exposed to 1 to 1000 MUM NO concentrations. Biofilms were
      visualized using Live/Dead Baclight stain and confocal scanning laser microscopy,
      and quantified using Comstat2, a biofilm quantification software. RESULTS:
      Biofilm biomass decreases from an average of 0.105 to 0.057 MUm(3) /MUm(2) at
      higher NO concentrations (125-1000 MUM), but is increased to 0.470 MUm(3) /MUm(2)
      at lower NO concentrations (0.9-2.0 MUM). The average biomass at high vs low
      concentrations are statistically significant (p < 0.001). CONCLUSION: S. aureus
      biofilm formation varies across exposure to different NO levels, with antibiofilm
      effects at higher concentrations, and enhanced biofilm formation at lower or
      subphysiologic concentrations. These results coincide with the often dualistic
      function of NO, and have implications in its future use in the treatment of CRS.

PMID- 22144053
TI  - Chronic rhinosinusitis with nasal polyps: elevated serum immunoglobulin E is
      associated with Staphylococcus aureus on culture.
AB  - BACKGROUND: Recent data has implicated Staphylococcus aureus (SA) superantigen as
      a potential disease modifier in patients with chronic rhinosinusitis (CRS) with
      nasal polyps (CRSwNP). The objective of this work was to compare total serum
      immunoglobulin E (IgE) and serum eosinophils in patients with CRSwNP and CRS
      without nasal polyps (CRSsNP) based on culture results of the 3 most commonly
      isolated bacteria. METHODS: Retrospective review at a tertiary rhinology referral
      center of patients with CRS over a 4-year period. RESULTS: Bacterial cultures and
      immunologic data were obtained from 62 patients with CRSwNP and 34 patients with
      CRSsNP. SA was the most prevalent bacteria in the CRSwNP group, isolated in 19
      patients (31%). Patients with elevated total serum IgE (>114 IU/mL) were more
      likely to have SA on culture (p = 0.04) in this population. The percent serum
      eosinophil levels in the SA+ group compared with the SA- group was not
      significant (6.0 vs 5.1, p = 0.17). Lund-Mackay computed tomography (CT) scores,
      but not Sino-Nasal Outcome Test 20 (SNOT-20) scores were significantly higher in
      the SA+ vs SA- group (p = 0.03) in patients with CRSwNP. The CRSsNP group
      demonstrated no difference in IgE or serum eosinophils between different
      bacterial groups. CONCLUSION: Our findings suggest that there is an association
      between SA sinonasal presence and elevated total serum IgE in patients with
      CRSwNP. In addition, SA+ patients had higher Lund-Mackay CT scores, indicating a
      higher objective burden of disease in this group of patients.

PMID- 22144054
TI  - Update on bacterial detection methods in chronic rhinosinusitis: implications for
      clinicians and research scientists.
AB  - BACKGROUND: The exact etiologic role of microbes in chronic rhinosinusitis (CRS)
      remains unclear, due in part to inconsistencies and difficulties of
      microbiological detection. However, methodological advances now permit
      comprehensive analysis of microbial communities of the sinonasal region. This
      review summarizes recent developments in microbial detection technologies as
      exemplified by their application in the study of CRS. RECENT FINDINGS: A variety
      of novel methods for specimen collection, microbial culture, cultivar
      identification, and microscopic analysis of CRS specimens have been used in
      recent studies. Moreover, the advent of culture-independent methodologies based
      on the detection of microbial nucleic acids has greatly expanded the range of
      microorganisms, including fastidious species, that can be assayed. Many
      techniques use biochemical interactions to identify nucleic acids as markers for
      specific species. SUMMARY: Technological innovations in microbiology have
      radically improved the sensitivity and accuracy of microbial detection and
      identification in CRS specimens. Further application of these microbiological
      tools to CRS research should provide greater insight into the roles of microbial
      pathogens and commensals in sinus health and disease. Ultimately, translation of
      research results into clinical diagnostic technology will improve patient
      outcomes in this chronic disease.

PMID- 22144055
TI  - First clinic experience: patient selection and outcomes for ostial dilation for
      chronic rhinosinusitis.
AB  - BACKGROUND: To report outcomes for subjects undergoing balloon dilation in either
      the operating room (OR) or the clinic and define criteria to identify suitable
      candidates for local anesthesia procedures. METHODS: Subjects with medically
      refractory chronic rhinosinusitis (CRS) underwent de novo surgery via transantral
      balloon dilation of the maxillary sinus ostium and ethmoid infundibulum.
      Concomitant nasal or endoscopic sinus surgeries were contraindicated. Technical
      success, surgical parameters, and long-term outcomes were evaluated through 12
      month follow-up. RESULTS: Seventy-one subjects underwent balloon dilation and 94%
      completed follow-up through 12 months. A total of 132 maxillary ostia were
      targeted for treatment and 129 were successfully dilated (98%). Almost one-half
      (33) of the procedures were performed in the OR under local anesthesia with
      intravenous sedation. Average balloon procedure times for unilateral and
      bilateral treatment were 28.3 +/- 21.1 and 40.2 +/- 17.7 minutes, respectively.
      Thirty-three ostial dilations in 19 subjects were attempted in the clinic. Each
      ostium was successfully accessed and ballooned under local anesthesia. Patient
      tolerance was very good with an average self-reported pain level of 2.7 (2 =
      hurts a little bit) out of 10. Each subject was discharged within 2 hours of the
      procedure and there was no postoperative bleeding. Symptomatic improvement of the
      clinic subgroup at 3, 6, and 12 months postprocedure was statistically
      significant (p <= 0.0012) and clinically meaningful and similar in magnitude to
      improvement seen across all subjects regardless of site of service. CONCLUSION:
      Transantral balloon dilation can be performed safely in the clinic and operative
      settings with symptom improvement sustained through 1 year.

PMID- 22144056
TI  - Unexpected consequences of transnasal balloon dilation of the maxillary ostium.
AB  - BACKGROUND: Nasal irrigations and topical sprays have been demonstrated to have
      benefit in chronic sinusitis. Increasingly, it is evident that delivery system,
      patient anatomy, and inflammatory process have significant impacts on irrigant
      distribution. METHODS: Intrasinus endoscopy was performed during sinus irrigation
      of 5 thawed fresh frozen cadavers (10 sides) before and after transnasal dilation
      of the maxillary, frontal, and sphenoid ostia with a 5-mm balloon. RESULTS:
      Guidewire insertion created false passages through maxillary fontanelle on all of
      10 attempts; 1 of 10 frontal insertions entered the ostia in a submucosal plane,
      while all 10 sphenoid attempts were successful without complication (p < 0.0001).
      Average minimum ostial dimension increased from 1.73 mm to 3.6 mm (p < 0.0001)
      after dilation. Obtaining an ostial size of 5 mm was associated with
      significantly improved irrigation penetration relative to a minimum dimension of
      4 mm or less (p = 0.019). After balloon dilation of the true ostia, irrigation of
      the sphenoid increased, irrigations into the frontal sinuses were unchanged, and
      irrigation into the maxillary sinuses decreased. CONCLUSION: Guidewire insertion
      in this study was noted to frequently create a false passage during maxillary
      sinus ostial dilation. After balloon dilation, irrigant penetration was increased
      into the sphenoid sinus for heavy and mist irrigators whereas the maxillary sinus
      had diminished irrigant penetration for heavy and NetiPot irrigators.

PMID- 22144057
TI  - Upfront computed tomography scanning is more cost-beneficial than empiric medical
      therapy in the initial management of chronic rhinosinusitis.
AB  - BACKGROUND: Current treatment algorithms for patients with symptoms of chronic
      rhinosinusitis (CRS) recommend a trial of empiric medical therapy prior to
      obtaining a sinus computed tomography (CT) scan, even in cases of negative nasal
      endoscopy. This empiric approach evolved in an era when same day conventional CT
      was both impractical and economically irresponsible. The objective of this work
      was to determine whether upfront CT scanning is more cost-beneficial than empiric
      medical therapy for patients presenting with CRS symptoms but negative endoscopic
      findings. METHODS: A Markov economic model was employed. Medication costs, CT
      costs, treatment response rates, and treatment associated adverse event rates
      were included as model parameters. Treatment cost values were derived from
      Medicare. RESULTS: There is a clear cost advantage to the upfront CT algorithm
      over empiric therapy regardless of the availability of point-of-care CT scanning
      (POC-CT). This advantage persists during the sensitivity analysis when costs and
      response rates are fully biased toward empiric therapy. If POC-CT is available,
      upfront CT can save $320.50 per patient (range, $138.5-671.5). When POC-CT CT is
      unavailable, upfront CT savings persist at $296.60 (range, $106.09-655.40).
      CONCLUSION: In patients meeting symptom criteria for CRS but without endoscopic
      evidence of inflammation, upfront CT scanning is more cost-beneficial than
      empiric medical therapy. Adopting upfront CT scanning can save the U.S.
      healthcare system $1.2 billion dollars per year. Further, POC-CT can offer same
      day diagnosis, facilitate prompt treatment, and decrease unnecessary antibiotic
      prescriptions.

PMID- 22144058
TI  - Prospective evaluation of intraoperative computed tomography imaging for
      endoscopic sinonasal and skull-base surgery.
AB  - BACKGROUND: The objective of this study was to prospectively evaluate the
      clinical impact of intraoperative computed tomography (CT) imaging on endoscopic
      sinonasal and skull base procedures. METHODS: A total of 49 patients were
      enrolled after informed consent from December 2009 to May 2010. Patients
      underwent intraoperative volume CT imaging (xCAT, Xoran Technologies, Ann Arbor,
      MI) at the conclusion of their proposed surgery. RESULTS: The mean age was 48.6
      years with male:female ratio of 1.3:1. Surgical procedures included revision or
      primary endoscopic sinonasal surgery (ESS) (36), endoscopic benign or malignant
      tumor resection (10), endoscopic mucocele drainage (2), and endoscopic tumor
      biopsy (1). The mean Lund-Mackay (L-M) score was 10.6 (range 1-21). The
      indications for intraoperative imaging included extent of paranasal sinus
      dissection in 38 (77.6%), extent of tumor resection in 11 (22.4%), adequacy of
      mucocele drainage in 3 (6.1%), and frontal stent position in 2 (4.1%) cases.
      Average acquisition time was 5.3 minutes. The CT acquisition quality was deemed
      excellent in 24 (49.0%), good in 15 (30.6%), fair in 5 (10.2%), and unattainable
      in 5 (10.2%) cases. Additional interventions were performed in 8 of 44 cases
      (18%) based on the intraoperative CT dataset. Analysis of predictive factors for
      additional intervention, including presence of polyps, presence of tumor,
      previous surgery, use of image guidance, and CT quality did not reach statistical
      significance. CONCLUSION: Intraoperative CT scanning may hold important utility
      in selected endoscopic sinonasal and skull base procedures with additional
      interventions being performed in 18% of cases. The present study was unable to
      identify specific factors that would preoperatively predict the need for
      intraoperative imaging. Future clinical trials should include a multi
      institutional design to better delineate these important variables.

PMID- 22144059
TI  - Radiological localization of Schneiderian papilloma.
AB  - BACKGROUND: It has been recently reported that the site of attachment of
      Schneiderian papillomas can be predicted with high accuracy on preoperative
      computed tomography (CT) scans using bony osteitic changes as an indicator. The
      objective of this study is to evaluate, in a blinded fashion, the reliability of
      the osteitis sign at predicting the site of attachment of Schneiderian
      papillomas. METHODS: A retrospective cohort study of patients who underwent
      endoscopic surgical resection for inverted papilloma (IP) or cylindrical
      papilloma between September 2002 and September 2009 in a tertiary care rhinology
      center was carried out. The preoperative sinus CT scans were collected and
      reviewed by a fellowship-trained and experienced head and neck radiologist who
      was blinded to the intraoperative findings. The radiologist attempted to identify
      and grade bony osteitic changes in the sinuses. The radiological findings were
      then correlated with the actual site of attachment reported by the surgeon in the
      operative report. RESULTS: A total of 34 patients were evaluated. Six (18%)
      patients had a single site of osteitis and 28 (82%) were found to have multiple
      sites of osteitis. The sensitivity and specificity of the radiological prediction
      based on the degree of osteitis was found to be 74% (46.5-90.3%) and 0% (0-17%),
      respectively. The predictive value of the radiological localization was 41%.
      CONCLUSION: Osteitic changes are very common nonspecific findings on CT scans of
      patients with Schneiderian papillomas. Their presence as well as the degree of
      osteitis did not allow preoperative localization of tumor attachment.

PMID- 22144060
TI  - Radiological localization of Schneiderian papilloma.

PMID- 22144061
TI  - Modified endoscopic medial maxillectomy for recalcitrant chronic maxillary
      sinusitis.
AB  - BACKGROUND: Modified endoscopic medial maxillectomy (MEMM) is an accepted
      alternative treatment for benign sinonasal neoplasms. Its use as definitive
      treatment for inflammatory disease of the maxillary sinus has yet to be
      adequately explored. We evaluate the efficacy of MEMM for chronic maxillary
      sinusitis and attempt to identify factors that predispose patients for failure.
      METHODS: A retrospective chart review of 46 patients who underwent a total of 61
      medial maxillectomies for recurrent chronic maxillary sinusitis from 2003 to 2010
      was performed. Data was collected regarding patient demographics, prior
      therapies, and exudative cultures. RESULTS: Complete resolution of disease was
      achieved in 37 of 46 patients (80%). Four patients required additional topical
      medical management prior to resolution of their inflammatory disease. When the
      culture was negative, resolution of disease was seen in 90% of patient. However
      if P. aeruginosa was cultured, the rate of disease resolution dropped to 75%.
      Similarly if S. aureus was culture, only 56% of patient demonstrated complete
      disease resolution. Of patients who had previous Caldwell-Luc procedures, 73%
      were successfully salvaged. No revision surgeries were required. The mean follow
      up time was 35 months. CONCLUSION: MEMM is an effective and acceptable
      alternative treatment for chronic maxillary sinusitis refractory to standard
      medical treatment and endoscopic surgical treatment. Cultures positive for P.
      aeruginosa and S. aureus may be associated with worse outcomes.

PMID- 22144062
TI  - Retrospective study of full-house functional endoscopic sinus surgery for
      revision endoscopic sinus surgery.
AB  - BACKGROUND: Outcomes for revision endoscopic sinus surgery (RESS) are rarely
      reported in relation to technique. Our goal was to document the outcome of full
      house functional endoscopic sinus surgery (FESS) (FHF) (complete
      sphenoethmoidectomy with Draf IIA frontal sinusotomy) for treatment of this
      recalcitrant group. METHODS: Twenty-one patients with chronic sinusitis having
      had at least 1 previous sinus surgery (mean, 2.14) underwent FHF, followed by
      postoperative nasal douching and oral antibiotics for 12 weeks. After a minimum 6
      months of follow-up, patients were asked to complete a 5-item Patient Response
      Score (PRS) (graded on a 6-point scale from 1 = completely improved to 6 = much
      worse). Objective measures collected included computed tomography (CT) Lund
      MacKay score (L-M score, LMS), and endoscopic findings: mucosal swelling (MS) and
      mucopus (MP) (graded on a 4-point scale from 0 = none to 3 = severe). RESULTS:
      Patients were divided into 3 subgroups based on months of follow up from surgery:
      6-12, 12-18, and 18-24. There was no statistical difference in any outcome based
      on length of follow up. Mean symptom outcome was reported as much improved (PRS =
      1.9 +/- 0.1). Both mucosal swelling and mucopus improved dramatically (2.48 vs
      0.29, p < 0.001; 2.52 vs 0.29, p < 0.001, respectively). LMS also improved
      dramatically (11.52 vs 2.1, p < 0.001). Presence of nasal polyps did not affect
      any subjective or objective outcome. CONCLUSION: Marked improvements in symptoms
      and mucosal findings were consistently obtained with FHF between 6 and 24 months
      postoperatively.

PMID- 22144064
TI  - [Quality of reporting of systematic reviews and meta-analyses: PRISMA (Preferred
      Reporting Items for Systematic reviews and Meta-Analyses)].

PMID- 22144065
TI  - [Introduction to the information technology working group].

PMID- 22144066
TI  - [Urogenital radiology in Deutsche Rontgengesellschaft].

PMID- 22144068
TI  - Carboxylation of arene C-H bonds with CO2: a DFT-based approach to catalyst
      design.
AB  - A prototypical catalytic cycle for the direct carboxylation of unactivated arene
      C-H bonds with CO(2) based on ruthenium(II) pincer complexes as catalysts is
      proposed and investigated by density functional theory (DFT) methods. The
      energetic span model is used to predict the turnover frequency (TOF) of various
      potential catalysts, evaluating their efficiency for this reaction. In addition
      to modifications of the catalyst structure, we also investigated the effect of
      the substrate, the solvent, and the influence of a base on the thermodynamics and
      kinetics of the reaction. Turnover frequencies in the range of 10(5)-10(7) h(-1)
      are predicted for the best systems. Alternative reaction pathways that might
      prevent the reaction are also investigated. In all cases, either the respective
      intermediates are found to be unstable or activation barriers are found to be
      very high, thereby indicating that these alternative pathways will not interfere
      with the proposed catalytic cycle. As a result, several ruthenium pincer
      complexes are suggested as very promising candidates for experimental
      investigation as catalysts for the carboxylation of arene C-H bonds with CO(2).

PMID- 22144069
TI  - A strategy to investigate the intravarietal genetic variability in Vitis vinifera
      L. for clones and biotypes identification and to correlate molecular profiles
      with morphological traits or geographic origins.
AB  - Grapevine is the most economically important and widely cultivated fruit crop in
      the world. Molecular markers have been used on Vitis vinifera to distinguish
      among both varieties and clones. Microsatellites are used to fingerprint
      varieties and several other techniques, reported in many papers, are used to
      analyze the differences among clones, but it is not available in the literature
      as a well defined strategy to screen a large number of Vitis cultivars. In fact,
      it is often necessary to use different techniques to investigate the genetic
      variability in different grapevine varieties and a proposed technique is used to
      study a cultivar, which is often not suitable for either the study of another
      cultivar or compare the genetic relationship among various cultivars. We describe
      here a strategy used for the analysis of several grapevine cultivars to describe
      a universal method to obtain DNA polymorphisms of Vitis vinifera genotypes from
      the same cultivar by using amplified fragment length polymorphism (AFLP),
      selective amplification of microsatellite polymorphic loci (SAMPL),
      microsatellites AFLP (M-AFLP), and ISSR molecular markers. The strategy here
      adopted permitted both to identify different biotypes (i.e., Primitivo),
      accessions (i.e., Garnacha tinta), and clones (i.e., Callet, Manto Negro, Moll)
      among the variability of same variety and to correlate the genetic differences to
      their geographical origins (i.e., Garnacha tinta; Malvasia nera di
      Brindisi/Lecce) or morphological traits (i.e., Malvasia of Candia). Here is also
      described the application of the protocol that allows to highlight the genetic
      variability accumulated during centuries of cultivations and selections of the
      same variety in different environments by vine growers.

PMID- 22144070
TI  - An improved protocol for the isolation of RNA from roots of tea (Camellia
      sinensis (L.) O. Kuntze).
AB  - Tea, a beverage crop, is a rich source of polyphenols and polysaccharides which
      greatly attribute to its importance. However, oxidation and precipitation of
      these compounds during nucleic acids extraction is a limitation to molecular
      biology and genomic studies. On isolation of total RNA from root tissue using
      established protocols, difficulties were encountered in terms of purity and
      quantity of isolated RNA or some of the methods were time-consuming and also
      yields were low. The present communication combines a phenol-based RNA isolation
      protocol with a cetyltrimethylammonium bromide-based procedure with appropriate
      modifications. This protocol successfully isolated RNA from tap root tissue in 2
      3 h as compared with 16 h reported by the previous method. Also, RNA yield was
      higher by more than fourfold. The RNA isolated by this protocol was successfully
      used for downstream applications such as RT-PCR and the construction of
      suppression subtractive hybridization library. The developed protocol worked well
      with other plant tissue with high polyphenols and polysaccharides contents.

PMID- 22144071
TI  - Immunomodulatory activities and antioxidant properties of polysaccharides from
      Monascus-fermented products in vitro.
AB  - BACKGROUND: Monascus-fermented products have featured in Chinese cuisine for
      thousands of years and are widely used as food colourants and dietary materials
      in many Asian countries. Rice and dioscorea fermented with Monascus purpureus NTU
      568 have health-promoting attributes in vitro and in vivo. The aim of this study
      was to investigate the immunomodulatory and antioxidant effects of
      polysaccharides from red mould rice (RMRP) and red mould dioscorea (RMDP) in Raw
      264.7 cells. RESULTS: The results showed the antioxidant capabilities (including
      scavenging, chelating, inhibition of lipid peroxidation, and reducing power) of
      RMRP and RMDP at a concentration of 10 mg mL(-1). RMRP and RMDP also stimulated
      cell proliferation, nitric oxide production, phagocytosis and cytokine production
      (including IL1-beta, IL-6 and TNF-alpha) in Raw 264.7 cells. CONCLUSION: These
      findings demonstrate that RMRP and RMDP have antioxidant and immunomodulation
      potential to be developed as novel dietary supplements.

PMID- 22144072
TI  - Modelling the effect of environmental factors on the hyphal growth of the
      basidiomycete Physisporinus vitreus.
AB  - The present work investigated the effects of environmental factors on the growth
      of fungal colonies of the white-rot basidiomycetes Physisporinus vitreus using a
      lattice-free discrete modeling approach called the fungal growth model (FGM), in
      which hyphae and nutrients are considered as discrete structures. A discrete
      modeling approach enables the underlying mechanistic rule concerning the basic
      architecture and dynamics of fungal networks to be studied on the scale of a
      single colony. By comparing simulations of the FGM with laboratory experiments of
      fungal colonies growing on malt extract agar we show that the combined effects of
      water activity, temperature and pH on the radial growth rate of fungal mycelia on
      the macroscopic scale may be explained by a power law for the costs of hyphal
      maintenance and expansion on the microscopic scale. Information about the
      response of the fungal mycelium at the micro- scopic level to environmental
      conditions is essential for simulating its behavior in complex structure
      substrates such as wood, where the effect of the fungus on the wood (i.e. the
      degradation of the cell wall) changes the local environmental condition (e.g. the
      permeability of the substrate and therefore the water activity in a colonized
      wood cell lumen). Using a combination of diffusion and moisture processes with
      the FGM may increase our understanding of the colonization strategy of P. vitreus
      and help to optimize its growth behavior for biotechnological applications such
      as bioincising.

PMID- 22144073
TI  - Exosomes as extrapulmonary signaling conveyors for nanoparticle-induced systemic
      immune activation.
AB  - Evaluation of systemic biosafety of nanomaterials urgently demands a
      comprehensive understanding of the mechanisms of the undesirable interference and
      systemic signaling that arises between man-made nanomaterials and biological
      systems. It is shown that exosomes may act as signal conveyors for nanoparticle
      induced systemic immune responses. Exosomes are extracellularly secreted membrane
      vesicles which act as Trojan horses for the dissemination and intercellular
      communication of natural nanosized particles (like viruses). Upon exposure to
      magnetic iron oxide nanoparticles (MIONs), it is possible to dose-dependently
      generate a significant number of exosomes in the alveolar region of BALB/c mice.
      These exosomes are quickly eliminated from alveoli into systemic circulation and
      largely transfer their signals to the immune system. Maturation of dendritic
      cells and activation of splenic T cells are significantly induced by these
      exosomes. Furthermore, exosome-induced T-cell activation is more efficient toward
      sensitized T cells and in ovalbumin (OVA)-sensitized mice than in the
      unsensitized counterparts. Activation of systemic T cells reveals a T helper 1
      polarization and aggravated inflammation, which poses potential hazards to the
      deterioration of allergic diseases in OVA-sensitized mice. The studies suggest
      that exosomes may act as conveyors for extrapulmonary signal transduction in
      nanoparticle-induced immune systemic responses, which are the key in vivo
      processes of manufactured nanoparticles executing either biomedical functions or
      toxic responses.

PMID- 22144076
TI  - Setting the stage: the role of ethics at work.

PMID- 22144074
TI  - VP16 serine 375 is a critical determinant of herpes simplex virus exit from
      latency in vivo.
AB  - Development of novel prevention and treatment strategies for herpes simplex virus
      (HSV) mediated diseases is dependent upon an accurate understanding of the
      central molecular events underlying the regulation of latency and reactivation.
      We have recently shown that the transactivation function of the virion protein
      VP16 is a critical determinant in the exit from latency in vivo. HSV-1 strain
      SJO2 carries a single serine to alanine substitution at position 375 in VP16
      which disrupts its interaction with its essential co-activator Oct-1. Here we
      report that SJO2 is severely impaired in its ability to exit latency in vivo.
      This result reinforces our prior observations with VP16 transactivation mutant,
      in1814, in which VP16 interaction with Oct-1 is also disrupted and solidifies the
      importance of the VP16-Oct-1 interaction in the early steps in HSV-1
      reactivation.

PMID- 22144075
TI  - Predicting toxicity from radiation therapy--it's genetic, right?

PMID- 22144077
TI  - Ethics at work: issues and insights across employment settings.

PMID- 22144078
TI  - Ethics of disability: foundation of the profession of speech-language pathology.
AB  - Ethics is a continuous and dynamic decision process that ultimately seeks to
      render a judgment about the morality of human conduct. A genre of applied ethics,
      social ethics is concerned with promoting societal morality, specifically
      ensuring the rights of disenfranchised groups such as people with disabilities.
      This article will examine concepts of ethical theory and practice and also trace
      the historical development and evolution of social ethics for disability. In its
      conclusion, this article will highlight the advocacy role of speech and language
      professionals to ensure an ethical response to disability.

PMID- 22144079
TI  - Promoting ethical research practices: perspectives from pediatric populations.
AB  - Engaging in research activities can be an enriching aspect of one's professional
      career. Research serves to advance the knowledge base from which clinical
      decisions are founded and is the responsibility of all who provide clinical
      services. That is, developing and advancing this knowledge base is everyone's
      responsibility, whether as consumers of research or as direct contributors of
      research. Understanding the ethical issues that embrace the research enterprise
      is a complementary responsibility of professionals. Conducting research within an
      ethical framework is essential to maintaining integrity and credibility in
      science. Opportunities to promote scientific integrity are particularly relevant
      when conducting or examining research involving children. Therefore, the purpose
      of this article is to provide an overview of the role of research in clinical
      practice, particularly in an environment with pediatric populations. The article
      will unfold with three major themes: (1) understanding the value of research in
      the clinical environment, (2) describing factors that contribute to sound ethical
      practices, and (3) promoting integrity in research conducted with pediatric
      populations.

PMID- 22144080
TI  - Ethical deliberation: a foundation for evidence-based practice.
AB  - Infusing evidence-based practice (EBP) into the clinical setting implies that
      professionals use evidence that is relevant and credible, maintain their pursuit
      of best current knowledge, respect their clients' preferences and values, and
      keep these clients and their families appropriately informed about their
      treatment options. Thus, rational and judicious EBP must be guided by speech
      language pathologists' or audiologists' ethical principles of beneficence, non
      maleficence, justice, and autonomy. In this article, we will affirm the
      centrality of ethical reasoning in EBP by describing what it means to be a
      professional as reflected in our Code of Ethics, reviewing the principles of
      ethics that underlie clinical decision making, and demonstrating how an ethical
      framework can and should provide the context in which EBP is conducted.

PMID- 22144081
TI  - Good ethical tone in the work setting.
AB  - Speech-language pathologists report a broad range of situations that they believe
      represent professional dilemmas. Some arise in their employment settings because
      of mandates and employment-related policies established by their employers,
      supervisors, and administrators. Their reports do not as often reflect the many
      instances where ethical problems associated with the workplace may occur because
      of the conduct and actions of speech-language pathologists themselves. The
      purpose of this article is to identify and discuss some common quandaries speech
      language pathologists and their employers may experience that are associated with
      workplace-related matters.

PMID- 22144082
TI  - Ethics in stuttering treatment in the schools: issues and intersections.
AB  - When the challenges of providing speech-language pathology services in school
      settings intersect with the complexities of meeting the unique needs of students
      who stutter, clinicians may encounter a variety of ethical issues. This article
      explores some of the ethical challenges of treating stuttering in school settings
      by discussing three clinical scenarios. Seedhouse's Ethics Grid is provided as a
      scaffold to support the critical analysis of school-based stuttering treatment
      issues. Factors examined include creating and respecting autonomy, serving
      student needs, doing good and minimizing risks, and telling the truth and keeping
      promises. In addition, clinical outcomes are considered in terms of their impact
      on students and family members, clinicians, students with communication disorders
      other than stuttering, and school personnel. Finally, some of the practical
      concerns when treating stuttering in school settings are discussed, including the
      law, codes of practice, wishes of others, as well as the effectiveness and
      efficiency of actions.

PMID- 22144083
TI  - Ethics in the practice of speech-language pathology in health care settings.
AB  - ETHICS refers to a moral philosophy or a set of moral principles that determine
      appropriate behavior in a society. Medical ethics includes a set of specific
      values that are considered in determining appropriate conduct in the practice of
      medicine or health care. Because the practice of medicine and medical speech
      language pathology affects the health, well-being, and quality of life of
      individuals served, adherence to a code of ethical conduct is critically
      important in the health care environment. When ethical dilemmas arise,
      consultation with a bioethics committee can be helpful in determining the best
      course of action. This article will help to define medical ethics and to discuss
      the six basic values that are commonly considered in discussions of medical
      ethics. Common ethical mistakes in the practice of speech-language pathology will
      be described. Finally, the value of a bioethics consultation for help in
      resolving complex ethical issues will be discussed.

PMID- 22144084
TI  - Ethical issues in the conduct of research at a multidisciplinary clinic.
AB  - We describe the process our interdisciplinary clinic used to create an
      institutional policy regarding research participant recruitment from among our
      client base. We demonstrate how certain elements of the client-clinician
      relationship can lead to inadvertent ethical quandaries in research recruitment,
      including implicit coercion and fostering of "therapeutic misconception." Our
      internal policy deliberations focused on five central dilemmas, each requiring a
      careful evaluation of ethical principles. Interpersonal and cross-disciplinary
      differences of opinion required a delicate balance among competing priorities.
      The final policy represents our attempt to resolve these ethical paradoxes in a
      way that allows us to support and pursue valuable clinician-researcher
      partnerships while prioritizing both our clients' clinical care and their rights
      to autonomy and fully informed consent.

PMID- 22144085
TI  - Ethical issues in a pediatric private practice.
AB  - Building a successful pediatric private practice requires clinical expertise and
      an understanding of the business process, as well as familiarity with the
      American Speech-Language-Hearing Association Code of Ethics. This article
      provides an overview of the ethical issues that may be encountered when building
      a practice, including a look at marketing and advertising, financial management,
      privacy, and documentation. Ethically sound decision making is a key to a
      successful business.

PMID- 22144088
TI  - Atypical squamous metaplasia in a benign cystic thyroid nodule mimicking high
      grade carcinoma.
AB  - Squamous metaplasia (SM) occurs in a variety of thyroid conditions, both
      neoplastic and non-neoplastic. In a small subset of benign thyroid lesions, SM
      can create a diagnostic pitfall by mimicking a malignant process. Here, we
      describe the case of a 52-year-old male with a 1.5 cm right thyroid nodule.
      Ultrasound-guided fine-needle aspiration biopsy showed markedly atypical,
      mitotically active epithelial cells which were suspicious for high-grade
      carcinoma. Resection of the nodule demonstrated a follicular adenoma with cystic
      changes and atypical SM of the cyst-lining component. As illustrated here, SM of
      the thyroid represents an important diagnostic pitfall for the cytopathologist,
      and should be included in the differential diagnosis of thyroid nodules,
      particularly those with potentially benign cystic changes.

PMID- 22144087
TI  - ProsCan for Couples: a feasibility study for evaluating peer support within a
      controlled research design.
AB  - BACKGROUND: The present study assessed the feasibility of delivering peer support
      for couples coping with prostate cancer within a trial design. METHODS/DESIGN:
      Ten peer volunteers completed training in research protocols and delivering tele
      based couples support to men with prostate cancer and their partners. Twenty
      couples received an eight session intervention and were assessed before surgery
      and 3 and 6 months subsequently for adjustment outcomes. A focus group
      investigated the peers' experiences. RESULTS: Peers were motivated by altruism, a
      belief in research, and reported personal growth. The research protocol at times
      conflicted with lay models of helping, and the focus on sexuality and couples was
      challenging. Distress decreased over time but more so for partners; unmet
      sexuality needs did not improve. CONCLUSION: Peer support appears promising as a
      model to support couples facing prostate cancer.

PMID- 22144089
TI  - Selective apoptosis in hepatic stellate cells mediates the antifibrotic effect of
      phenanthrenes from Dendrobium nobile.
AB  - Regardless of the etiology, cellular death of the liver parenchymal hepatocyte
      seems to be a primary event of hepatic fibrogenesis, which ultimately results in
      hepatic stellate cell (HSC) activation and the synthesis of extracellular matrix
      proteins. Recently it has been demonstrated that hepatic fibrosis can be a
      reversible process when the stimulus is properly eliminated. Apoptotic removal of
      active HSC is considered an essential part of the resolution. By employing the
      HSC cell line, HSC-T6, it was found that the methanol extract of Dendrobium
      nobile stem significantly inhibited the proliferation of HSC-T6 cells. Three
      phenanthrenes, denbinobin, fimbriol B and 2,3,5-trihydroxy-4,9
      dimethoxyphenanthrene isolated from D. nobile were proven to inhibit HSC
      proliferation. Growth arrest of HSCs by these compounds was accompanied by
      cellular loss via autophagy-linked apoptosis. The maximal dose of these
      compounds, however, had little effect on primary cultured hepatocytes in rats.
      Collagen deposition in HSC-T6 cells was attenuated by these phenanthrenes.
      Collectively, the above results demonstrated that denbinobin, fimbriol B and
      2,3,5-trihydroxy-4,9-dimethoxyphenanthrene exhibited antifibrotic activities
      possibly by the induction of selective cell death in HSCs but not in hepatocytes,
      implying that these compounds may be useful candidates for developing therapeutic
      agents for the prevention and treatment of hepatic fibrosis.

PMID- 22144090
TI  - CrkI and p130(Cas)  complex regulates the migration and invasion of prostate
      cancer cells.
AB  - Prostate cancer metastasis is often associated with poor prognosis. The molecular
      coupling of the adaptor protein Crk to the docking protein p130(Cas) serves as a
      switch that regulates cell migration in several invasive cancer cells and Ack
      appears to act upstream of CrkII to modulate the cell motility. However, the
      precise role of Ack, Crk and p130(Cas) complex in prostate cancer migration
      remains unknown. In this study we examined the expression of Crk and p130(Cas) in
      prostate cancer cell lines, and found that CrkI and p130(Cas) protein level was
      higher in highly invasive PC-3M and PC-3 cell lines than in moderately invasive
      DU-145 cells. Upon shRNA mediated knockdown of CrkI and p130(Cas) in PC-3M cells,
      cell migration and invasion were significantly inhibited as analyzed by wound
      healing assay and transwell invasion assay. Furthermore, co-immunoprecipitation
      assay showed that p130(Cas) interacted with CrkI in PC-3M cells and the stability
      of p130(Cas) and CrkI depended on each other. AckI interacted with both CrkI and
      p130(Cas) and the interaction of AckI with CrkI seemed to be independent of
      p130(Cas) . Taken together, our results demonstrate the high expression of CrkI
      and p130(Cas) in invasive prostate cancer cells and the important role of
      CrkI/p130(Cas) complex in the migration and invasion of prostate cancer cells.
      These data suggest that CrkI/p130(Cas) could be exploited as potential molecular
      therapeutic target for prostate cancer metastasis.

PMID- 22144091
TI  - Polypyrrole/polyamide electrospun-based sorbent for microextraction in packed
      syringe of organophosphorous pesticides from aquatic samples.
AB  - A novel method based on microextraction in packed syringe (MEPS) as sample
      preparation technique coupled off-line with gas chromatography-mass spectrometry
      was developed using electrospun nanofibers as sorbent. For electrospinning of
      polypyrrole/polyamide-based nanofiber, a homogeneous solution containing nylon 6,
      ferric chloride and pyrrole monomer was prepared and then was drawn into a 2.5-mL
      syringe. By applying a voltage of 13 kV between the needle of the syringe and an
      aluminum-foil collector, the nanofibers could be formed on the surface of the
      collector. The prepared sheet was used as the sorbent for MEPS to analyze some
      selected organophosphorous pesticides. Important parameters influencing the
      extraction and desorption processes were optimized. Limits of detection were in
      the range of 0.04-0.1 ng/mL using time scheduled selected ion monitoring mode,
      and the relative standard deviation (RSD %) values with four replicates were in
      the range of 3.7-11.8% at a concentration level of 5 ng/mL. The linearity of the
      method was in the range of 0.5-500 ng/mL for diazinon and fenithrothion and 0.5
      200 ng/mL for the rest of the analytes. The developed method was successfully
      applied to Zayandeh-roud river water samples, whereas the matrix factors were in
      the range of 0.87-0.98.

PMID- 22144092
TI  - Astrocyte stellation, a process dependent on Rac1 is sustained by the regulated
      exocytosis of enlargeosomes.
AB  - Cultured astrocytes exhibit a flat/epitelioid phenotype much different from the
      star-like phenotype of tissue astrocytes. Upon exposure to treatments that affect
      the small GTPase Rho and/or its effector ROCK, however, flat astrocytes undergo
      stellation, with restructuring of cytoskeleton and outgrowth of processes with
      lamellipodia, assuming a phenotype closer to that exhibited in situ. The
      mechanisms of this change are known only in part. Using the ROCK blocker drug
      Y27632, which induces rapid (tens of min), dose-dependent and reversible
      stellations, we focused on two specific aspects of the process: its dependence on
      small GTPases and the large surface expansion of the cells. Contrary to previous
      reports, we found stellation to be governed by the small G protein Rac1, up to
      disappearance of the process when Rac1 was downregulated or blocked by a specific
      drug. In contrast cdc42, the other G-protein often involved in phenotype changes,
      appeared not involved. The surface expansion concomitant to cytoskeleton
      restructuring, also dependent on Rac1, was found to be at least partially
      sustained by the exocytosis of enlargeosomes, small vesicles distinct from
      classical cell organelles, which are abundant in astrocytes. Exhaustion of
      stellation induced by repeated administrations of Y27632 correlated with the
      decrease of the enlargeosome pool. A whole-cell process like stellation of
      cultured astrocytes might be irrelevant in the brain tissue. However, local
      restructuring of the cytoskeleton coordinate with surface expansion, occurring at
      critical cell sites and sustained by mechanisms analogous to those of stellation,
      might be of importance in both astrocyte physiology and pathology.

PMID- 22144094
TI  - Genomic aberrations in normal appearing mucosa fields distal from oral
      potentially malignant lesions.
AB  - OBJECTIVES: Oral fields of visually normal and non-dysplastic mucosa (ODFs) may
      represent the precursors of oral potentially malignant lesions (OPMLs). Aim of
      the study was to provide new evidence for the concept of the "field
      carcinogenesis" model by comparing the ODF and OPML genomic aberration profiles
      obtained by high resolution DNA flow cytometry (hr DNA-FCM) and array-Comparative
      Genomic Hybridization (a-CGH). A second aim was to investigate if specific CGH
      aberrations were associated with DNA aneuploidy. METHODS: Nineteen patients with
      single OPMLs were recruited for the study. In parallel with obtaining samples of
      OPML tissue from 11 leukoplakias without dysplasia (nd-OPMLs) and 8 with
      dysplasia (d-OPMLs), we also obtained samples from distant ODFs. DNA aneuploid
      nuclei detected by hr DNA-FCM were physically separated, based on DNA content,
      from the DNA diploid components with a DNA-FCM-Sorter. These relatively pure
      subpopulations of epithelial nuclei were then submitted to DNA extraction and a
      CGH for a genome-wide analysis of DNA copy number aberrations (CNAs). RESULTS:
      The frequencies of DNA aneuploidy (DI ? 1) among ODFs and OPMLs were respectively
      5.3% and 32%. The DI aneuploid values of ODFs and nd-OPMLs were all near-diploid
      (DI ? 1 and DI <= 1.4), while for d-OPMLs were high-aneuploid (DI > 1.4) in 40%
      of the cases. CNA averages were 1.9 in ODFs and 6.5 in OPMLs. The gain of the
      chromosomal region 20q13.33-qter was observed in 37% of both ODFs and
      corresponding OPMLs. Additional common regions included 7p22.2-pter, 11p15.5-pter
      and 16p13.3-pter where gains were observed. Furthermore, gains of 20q13.31-q13.33
      and of 5p13.33-pter and loss of 9p21.3 were detected at high frequency
      (respectively, at 62.5%, 50% and 50%) only in d-OPMLs. In particular, loss at
      9p21.3, gain at 5p13.33-pter and gain of 20q13.31-q13.33 were associated with DNA
      aneuploidy (p = 0.00004; p = 0.0005; p = 0.01). CONCLUSIONS: ODFs and OPMLs
      showed common CNAs in specific chromosomal regions suggesting that they may
      represent early events of the natural history of oral carcinogenesis according to
      the field effect cancerization and may contribute to the ODF-OPML transition. In
      addition, loss at 9p21.3 and gains at 5p13.33-pter and 20q13.31-q13.33 may
      contribute to DNA aneuploidization.

PMID- 22144095
TI  - Tim-1 regulates Th2 responses in an airway hypersensitivity model.
AB  - T-cell immunoglobulin mucin-1 (Tim-1) is a transmembrane protein postulated to be
      a key regulator of Th2-type immune responses. This hypothesis is based in part
      upon genetic studies associating Tim-1 polymorphisms in mice with a bias toward
      airway hyperrespon-siveness (AHR) and the development of Th2-type CD4(+)  T
      cells. Tim-1 expressed by Th2 CD4(+)  T cells has been proposed to function as a
      co-stimulatory molecule. Tim-1 is also expressed by B cells, macrophages, and
      dendritic cells, but its role in responses by these cell types has not been
      firmly established. Here, we generated Tim-1-deficient mice to determine the role
      of Tim-1 in a murine model of allergic airway disease that depends on the
      development and function of Th2 effector cells and results in the generation of
      AHR. We found antigen-driven recruitment of inflammatory cells into airways is
      increased in Tim-1-deficient mice relative to WT mice. In addition, we observed
      increased antigen-specific cytokine production by splenocytes from antigen
      sensitized Tim-1-deficient mice relative to those from controls. These data
      support the conclusion that Tim-1 functions in pathways that suppress recruitment
      of inflammatory cells into the airways and the generation or activity of CD4(+) 
      T cells.

PMID- 22144096
TI  - Calcitonin measurement on fine needle washouts: preanalytical issues and normal
      reference values.
AB  - Calcitonin (CT) measurement on fine-needle aspiration cytology (FNAC) washouts
      (FNAC-CT) is a promising tool in the diagnosis of medullary thyroid carcinoma
      (MTC). Guidelines for the method with codified cut-off are needed to use this
      technique in clinical routine. This study was undertaken to assess the best pre
      analytical procedure and to define a reliable reference value for FNAC-CT. Fifty
      four patients underwent thyroid surgery, so MTC was excluded by surgical
      pathology examination and CT immunostains. Before surgery, FNAC-CT was measured
      on 78 thyroid nodules from such 54 patients. Needles were rinsed by normal saline
      and specific CT-free dilution buffer, and CT was measured by a fully automated
      immunochemiluminometric assay. FNAC-CT levels were not significantly different in
      normal saline or specific buffer. The calculated 97.5th upper FNAC-CT value was
      8.5 pg/mL (saline) and 7.43 pg/mL (buffer), respectively. Seeing its relatively
      large sample size, rigorous selection criteria and inclusion of CT immunostaining
      of thyroid nodules, the present study provides a reliable guideline and a
      clinically relevant reference value for FNAC-CT measurement in thyroid nodules.

PMID- 22144097
TI  - Ampelopsin inhibits H2O2-induced apoptosis by ERK and Akt signaling pathways and
      up-regulation of heme oxygenase-1.
AB  - Oxidative stress plays an important role in neurodegenerative disorders.
      Ampelopsin, a flavonoid abundant in Rattan tea (Ampelopsis grossedentata), is a
      potent antioxidant and its neuroprotective effect against H2O2-induced apoptosis
      in PC12 cells is investigated here for the first time. It was found that
      treatment of cells with ampelopsin for 1 h significantly reduced the loss of
      vitality, LDH release and apoptosis and inhibited the formation of reactive
      oxygen species (ROS). Ampelopsin was able to prevent the activation of p38
      induced by H2O2. In addition, up-regulation of heme oxygenase-1 (HO-1) expression
      by ampelopsin was shown to be both dose- and time-dependent. Mechanically, HO-1
      expression induced by ampelopsin was found to be due to activation of the ERK and
      Akt signaling pathways, because it was almost completely blocked by the specific
      inhibitors of ERK and Akt. These results suggest that ampelopsin increases
      cellular antioxidant defense through activation of the ERK and Akt signaling
      pathways, which induces HO-1 expression and thereby protects PC12 cells from H2O2
      induced apoptosis.

PMID- 22144098
TI  - Recent approaches in sensitive enantioseparations by CE.
AB  - The latest strategies and instrumental improvements for enhancing the detection
      sensitivity in chiral analysis by CE are reviewed in this work. Following the
      previous reviews by Garcia-Ruiz et al. (Electrophoresis 2006, 27, 195-212) and
      Sanchez-Hernandez et al. (Electrophoresis 2008, 29, 237-251; Electrophoresis
      2010, 31, 28-43), this review includes those papers that were published during
      the period from June 2009 to May 2011. These works describe the use of offline
      and online sample treatment techniques, online sample preconcentration techniques
      based on electrophoretic principles, and alternative detection systems to UV-Vis
      to increase the detection sensitivity. The application of the above-mentioned
      strategies, either alone or combined, to improve the sensitivity in the
      enantiomeric analysis of a broad range of samples, such as pharmaceutical,
      biological, food and environmental samples, enables to decrease the limits of
      detection up to 10-12 M. The use of microchips to achieve sensitive chiral
      separations is also discussed.

PMID- 22144099
TI  - Promiscuity in protein-RNA interactions: conformational ensembles facilitate
      molecular recognition in the spliceosome: conformational diversity in U2AF65
      facilitates binding to diverse RNA sequences.
AB  - Here I discuss findings that suggest a universal mechanism for proteins (and RNA)
      to recognize and interact with various binding partners by selectively binding to
      different conformations that pre-exist in the free protein's conformational
      ensemble. The tandem RNA recognition motif domains of splicing factor U2AF65
      fluctuate in solution between a predominately closed conformation in which the
      RNA binding site of one of the domains is blocked, and a lowly populated open
      conformation in which both RNA binding pockets are accessible. RNA binding to
      U2AF65 may thus occur through the weakly populated open conformation, and the
      binding interaction stabilizes the open conformation. The conformational
      diversity observed in U2AF65 might also facilitate binding to diverse RNA
      sequences as found in the polypyrimidine tracts that help define 3' splice sites.
      Similar binding pathways in other systems have important consequences in
      biological regulation, molecular evolution, and information storage.

PMID- 22144100
TI  - Highly porous silica-polyaniline nanocomposite as a novel solid-phase
      microextraction fiber coating.
AB  - A highly porous fiber-coated SBA-15/polyaniline material was prepared for solid
      phase microextraction (SPME). The SBA-15/polyaniline nanocomposite was
      synthesized via chemical polymerization. The prepared SBA-15/polyaniline
      particles were analyzed by scanning electron microscopy analysis. The prepared
      nanomaterial was immobilized onto a stainless steel wire for fabrication of the
      SPME fiber. The fiber was evaluated for the extraction of some polycyclic
      aromatic hydrocarbons (PAHs) from aqueous sample solutions in combination with
      gas chromatography-mass spectrometry (GC-MS). In optimum conditions (extraction
      temperature 60 degrees C, extraction time 40 min, ionic strength 20%, stirring
      rate: 500 rpm, desorption temperature 260 degrees C, desorption time 2 min), the
      repeatability for one fiber (n=3), expressed as relative standard deviation
      (RSD%), was between 5.3 and 8.6% for the test compounds. For deionized water,
      spiked with selected PAHs, the detection limits for the studied compounds were
      between 2 and 20 pg/mL.

PMID- 22144102
TI  - Cytomorphological features of an aggressive variant of polymorphous low-grade
      adenocarcinoma in adolescence with lymph node metastasis.

PMID- 22144101
TI  - Erk1/2 MAPK and mTOR signaling sequentially regulates progression through
      distinct stages of oligodendrocyte differentiation.
AB  - Myelination is the culmination of a complex process in which oligodendrocyte (OL)
      progenitors transition through defined stages in a well-coordinated
      differentiation program. The signaling mechanisms that regulate this progression
      are poorly understood. Here we investigate the role of extracellular signal
      regulated-kinase-1,-2 (Erk1/2) and the mammalian target of rapamycin (mTOR),
      downstream effectors of the Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways, at
      specific stages of OL development in vitro. Using a panel of developmental stage
      specific antigenic markers and pharmacological inhibitors, we provide evidence
      that Erk1/2 signaling regulates transition of early progenitors to the late
      progenitor stage and, as a consequence, to the immature OL stage, but not the
      transition of immature OL to the mature OL stage. In contrast, mTOR signaling is
      not required for early progenitor transition to late progenitor stage.
      Surprisingly, it is also not required for the transition of late progenitors to
      terminally differentiated immature OLs, as has been reported previously, but is
      required for the next sequential transition of immature OLs to the mature OL
      stage. Furthermore, mTOR signaling regulates OL cytoskeletal organization and
      major myelin protein expression. These in vitro findings correlate with our in
      vivo data showing that inhibition of mTOR by rapamycin injection attenuated the
      onset of myelination in the early postnatal brain. Thus, these studies
      demonstrate that Erk1/2 and mTOR signaling sequentially regulates distinct stages
      of OL progenitor differentiation and suggest that cells in the OL-lineage require
      distinct signaling mechanisms to transition through specific stages of their
      development.

PMID- 22144103
TI  - Extraction of antioxidants from spruce (Picea abies) bark using eco-friendly
      solvents.
AB  - INTRODUCTION: Antioxidants are known to avert oxidation processes and they are
      found in trees and other plant materials. Tree bark is a major waste product from
      paper pulp industries; hence it is worthwhile to develop an extraction technique
      to extract the antioxidants. OBJECTIVE: To develop a fast and environmentally
      sustainable extraction technique for the extraction of antioxidants from bark of
      spruce (Picea abies) and also to identify the extracted antioxidants that are
      abundant in spruce bark. METHODOLOGY: A screening experiment that involved three
      different techniques was conducted to determine the best technique to extract
      antioxidants. The antioxidant capacity of the extracts was determined with DPPH
      (2,2-diphenyl-1-picrylhydrazyl) assay. Pressurised fluid extraction (PFE) turned
      out to be the best technique and a response surface design was therefore utilised
      to optimise PFE. Furthermore, NMR and HPLC-DAD-MS/MS were applied to identify the
      extracted antioxidants. RESULTS: PFE using water and ethanol as solvent at 160
      and 180 degrees C, respectively, gave extracts of the highest antioxidant
      capacity. Stilbene glucosides such as isorhapontin, piceid and astringin were
      identified in the extracts. CONCLUSION: The study has shown that PFE is a fast
      and environmentally sustainable technique, using water and ethanol as solvent for
      the extraction of antioxidants from spruce bark.

PMID- 22144104
TI  - (1) H-NMR analysis of terpene trilactones (TTLs) in Ginkgo biloba: green female
      leaves contain the most TTLs.
AB  - INTRODUCTION: Terpene trilactones (TTLs), unique components of Ginkgo biloba
      extracts, are believed to play important roles in the biological activity of
      these materials. The investigation of seasonal and gender-related variations in
      the natural content of TTLs in the leaves is a challenging problem that must be
      addressed in order to establish more efficient extraction/isolation protocols for
      TTLs. OBJECTIVE: The aims of this work were (i) to modify the
      extraction/isolation protocols of TTLs from G. biloba leaves by means of boiling
      and filtration procedures, and (ii) to investigate seasonal and gender-related
      variations in the TTL content of the leaves via (1) H-NMR analysis. METHODOLOGY:
      When extracting TTLs from G. biloba leaves, procedures for boiling and filtration
      were improved in this work. Moreover, quantitative (1) H-NMR analysis using DMF
      as a reference was performed and correlated to the colour (green/yellow) and
      gender (male/female) variations in the natural compositions of TTLs in the
      leaves. RESULTS: Extraction procedures were modified to include boiling in ethyl
      acetate and filtration was achieved with celite. (1) H-NMR analysis of TTLs
      suggested that green female leaves contained the largest amount of TTLs, while no
      TTLs were present in yellow male leaves. CONCLUSION: The present results provide
      a method for quickly supplying laboratory-scale quantities of TTLs from natural
      sources to enable the study of their structure-activity relationships.

PMID- 22144105
TI  - Differential effects of inhibition of bone morphogenic protein (BMP) signalling
      on T-cell activation and differentiation.
AB  - Bone morphogenetic proteins (BMPs) are involved in patterning and cellular fate
      in various organs including the thymus. However, the redundancy of BMPs and their
      receptors have made it difficult to analyse their physiological roles. Here, we
      investigated the role of BMP signalling in peripheral CD4(+)  T cells by
      analysing the effects of an inhibitor of BMP signalling, dorsomorphin.
      Dorsomorphin suppressed phosphorylation of SMAD1/5/8, suggesting that BMP
      signalling naturally occurs in T cells. At high doses, dorsomorphin suppressed
      proliferation of T cells in a dose-dependent manner, inducing G1 arrest. Also,
      dorsomorphin suppressed Th17 and induced Treg-cell differentiation, while
      preserving Th2 differentiation. Dorsomorphin efficiently suppressed IL-2
      production even at low doses in mouse CD4(+)  T cells, suggesting that the BMP
      Smad signalling physiologically regulates IL-2 transcription in these cells. In
      addition, recombinant BMP2 induced a dose-dependent multiphasic pattern of IL-2
      production, while Noggin suppressed IL-2 production at higher doses in Jurkat
      cells. Notably, BMP signalling controlled the phosphorylation of RUNX1, revealing
      the molecular nature of its effect. Collectively, we describe multiple effects of
      dorsomorphin and Noggin on T-cell activation and differentiation, demonstrating a
      physiological role for BMP signalling in these processes.

PMID- 22144106
TI  - Alder-ene reaction: aromaticity and activation-strain analysis.
AB  - We have computationally explored the trend in reactivity of the Alder-ene
      reactions between propene and a series of seven enophiles using density
      functional theory at M06-2X/def2-TZVPP. The reaction barrier decreases along the
      enophiles in the order H(2) C=CH(2) > HC=CH > H(2) C=NH > H(2) C=CH(COOCH(3) ) >
      H(2) C=O > H(2) C=PH > H(2) C=S. Thus, barriers drop in particular, if third
      period atoms become involved in the double bond of the enophile. Activation
      strain analyses show that this trend in reactivity correlates with the activation
      strain associated with deforming reactants from their equilibrium structure to
      the geometry they adopt in the transition state. We discuss the origin of this
      trend and its relationship with the extent of synchronicity between H transfer
      from ene to enophile and the formation of the new C-C bond.

PMID- 22144107
TI  - Expression of paramyxovirus V proteins promotes replication and spread of
      hepatitis C virus in cultures of primary human fetal liver cells.
AB  - Here we demonstrate that primary cultures of human fetal liver cells (HFLC)
      reliably support infection with laboratory strains of hepatitis C virus (HCV),
      although levels of virus replication vary significantly between different donor
      cell preparations and frequently decline in a manner suggestive of active viral
      clearance. To investigate possible contributions of the interferon (IFN) system
      to control HCV infection in HFLC, we exploited the well-characterized ability of
      paramyxovirus (PMV) V proteins to counteract both IFN induction and antiviral
      signaling. The V proteins of measles virus (MV) and parainfluenza virus 5 (PIV5)
      were introduced into HFLC using lentiviral vectors encoding a fluorescent
      reporter for visualization of HCV-infected cells. V protein-transduced HFLC
      supported enhanced (10 to 100-fold) levels of HCV infection relative to
      untransduced or control vector-transduced HFLC. Infection was assessed by
      measurement of virus-driven luciferase, by assays for infectious HCV and viral
      RNA, and by direct visualization of HCV-infected hepatocytes. Live cell imaging
      between 48 and 119 hours postinfection demonstrated little or no spread of
      infection in the absence of PMV V protein expression. In contrast, V protein
      transduced HFLC showed numerous HCV infection events. V protein expression
      efficiently antagonized the HCV-inhibitory effects of added IFNs in HFLC. In
      addition, induction of the type III IFN, IL29, following acute HCV infection was
      inhibited in V protein-transduced cultures. CONCLUSION: These studies suggest
      that the cellular IFN response plays a significant role in limiting the spread of
      HCV infection in primary hepatocyte cultures. Strategies aimed at dampening this
      response may be key to further development of robust HCV culture systems,
      enabling studies of virus pathogenicity and the mechanisms by which HCV spreads
      in its natural host cell population.

PMID- 22144108
TI  - Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a
      randomized trial comparing 3- and 6-month periodicities.
AB  - Detection of small hepatocellular carcinoma (HCC) eligible for curative treatment
      is increased by surveillance, but its optimal periodicity is still debated. Thus,
      this randomized trial compared two ultrasonographic (US) periodicities: 3 months
      versus 6 months. A multicenter randomized trial was conducted in France and
      Belgium (43 sites). Patients with histologically proven compensated cirrhosis
      were randomized into two groups: US every 6 months (Gr6M) or 3 months (Gr3M). For
      each focal lesion detected, diagnostic procedures were performed according to
      European Association for the Study of the Liver guidelines. Cumulative incidence
      of events was estimated, then compared using Gray's test. The prevalence of HCC
      <=30 mm in diameter was the main endpoint. A sample size of 1,200 patients was
      required. A total of 1,278 patients were randomized (Gr3M, n = 640; Gr6M, n =
      638; alcohol 39.2%, hepatitis C virus 44.1%, hepatitis B virus 12.5%). At least
      one focal lesion was detected in 358 patients (28%) but HCC was confirmed in only
      123 (9.6%) (uninodular 58.5%, <=30 mm in diameter 74%). Focal-lesion incidence
      was not different between Gr3M and Gr6M groups (2-year estimates, 20.4% versus
      13.2%, P = 0.067) but incidence of lesions <=10 mm was increased (41% in Gr3M
      versus 28% in Gr6M, P = 0.002). No difference in either HCC incidence (P = 0.13)
      or in prevalence of tumors <=30 mm in diameter (79% versus 70%, P = 0.30) was
      observed between the randomized groups. CONCLUSION: US surveillance, performed
      every 3 months, detects more small focal lesions than US every 6 months, but does
      not improve detection of small HCC, probably because of limitations in recall
      procedures.

PMID- 22144109
TI  - Hypoxia-inducible microRNA-210 augments the metastatic potential of tumor cells
      by targeting vacuole membrane protein 1 in hepatocellular carcinoma.
AB  - As the "master" microRNA that is induced by hypoxia, miR-210 is involved in
      multiple processes in the hypoxia pathway. However, whether miR-210 mediates
      hypoxia-induced tumor cell metastasis still remains unclear. Here, we demonstrate
      that miR-210 is frequently up-regulated in hepatocellular carcinoma (HCC) samples
      and promotes the migration and invasion of HCC cells. Furthermore, miR-210 can be
      induced by hypoxia in HCC cells and mediates hypoxia-induced HCC cell metastasis.
      We identify vacuole membrane protein 1 (VMP1) as the direct and functional
      downstream target of miR-210; in addition, we show that its expression is
      negatively correlated with the expression of miR-210 in HCC. Intriguingly, VMP1
      is reduced by hypoxia, and down-regulation of VMP1 by miR-210 mediates hypoxia
      induced HCC cell metastasis. CONCLUSION: These findings extend our understanding
      of the function of miR-210 in the hypoxia pathway, and this newly identified
      hypoxia/miR-210/VMP1 pathway should facilitate the development of novel
      therapeutics against hypoxic tumor cells.

PMID- 22144110
TI  - Comparison of dispersive liquid-liquid microextraction based on organic solvent
      and ionic liquid combined with high-performance liquid chromatography for the
      analysis of emodin and its metabolites in urine samples.
AB  - In this paper, two methods based on organic solvent dispersive liquid-liquid
      microextraction (OS-DLLME) and ionic liquid dispersive liquid-liquid
      microextraction (IL-DLLME) coupled with high-performance liquid chromatography
      have been critically compared for analyzing emodin and its metabolites (aloe
      emodin, anthraquinone-2-carboxylic acid, rhein, danthron, chrysophanol and
      physcion) in urine samples. Several important parameters influencing the
      extraction recoveries of DLLME were carefully optimized. Under optimal
      conditions, the enrichment factors (EFs) for emodin and its metabolites by OS
      DLLME and IL-DLLME were within the range of 90-295 and 63-192 respectively; the
      relative standard deviations (RSDs, n=3) for intra-day and inter-day precision
      were lower than 7.2 and 8.7% by OS-DLLME, and lower than 5.7 and 6.4% by IL
      DLLME; the recoveries of emodin and its metabolites were from 87.1 to 105% for OS
      DLLME and from 94.8 to 103% for IL-DLLME, respectively. There were no significant
      deviations between the two methods for the determination of emodin and its
      metabolites. From the results of HPLC/UV of urine sample after DLLME, the
      metabolites aloe-emodin, rhein, chrysophanol and physcion were identified by
      comparing the retention times with the standards. From the results of HPLC/MS,
      anthraquinone-2-carboxylic acid and danthron as unreported metabolites of emodin
      were found.

PMID- 22144111
TI  - Efficient enrichment of phosphopeptides by magnetic TiO2-coated carbon
      encapsulated iron nanoparticles.
AB  - Titanium dioxide (TiO2) has been widely used for phosphopeptide enrichment.
      Several approaches have been reported to produce magnetic TiO2 affinity probes.
      In this report, we present a facile approach to immobilize TiO2 onto poly(acrylic
      acid)-functionalized magnetic carbon-encapsulated iron nanoparticles as affinity
      probes for efficient enrichment of phosphopeptides. By using the new magnetic
      TiO2 affinity probes, denoted as TiO2-coated Fe@CNPs, rapid and effective MALDI
      TOF MS profiling of phosphopeptides was demonstrated in different model systems
      such as tryptic digests of beta-casein, and complex beta-casein/BSA mixture. The
      TiO2-coated Fe@CNPs out-performed the commercial TiO2-coated magnetic beads for
      detection of phosphopeptides from tryptic digests of beta-casein/BSA mixture with
      a molar ratio of 1:100. The new TiO2-coated magnetic probes were also proven to
      be applicable for real life samples. The magnetic TiO2-coated Fe@CNPs were
      employed to selectively isolate phosphopeptides from tryptic digests of HeLa cell
      lysates and out-performed the commercial magnetic TiO2 beads in the number of
      identified phosphopeptides and phosphorylation sites. In a 200-MUg equivalent of
      HeLa cell lysates, we identified 1415 unique phosphopeptides and 1093
      phosphorylation sites, indicating the good performance of the new approach.

PMID- 22144113
TI  - Molecular mechanism of HIV-1 integrase-vDNA interactions and strand transfer
      inhibitor action: a molecular modeling perspective.
AB  - Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an essential enzyme
      for splicing a viral DNA (vDNA) replica of its genome into host cell chromosomal
      DNA (hDNA) and has been recently recognized as a promising therapeutic target for
      developing anti-AIDS agents. The interaction between HIV-1 IN and vDNA plays an
      important role in the integration process of the virus. However, a detailed
      understanding about the mechanism of this interactions as well as the action of
      the anti-HIV drug raltegravir (RAL, approved by FDA in 2007) targeting HIV-1 IN
      in the inhibition of the vDNA strand transfer is still absent. In the present
      work, a molecular modeling study by combining homology modeling, molecular
      dynamics (MD) simulations with molecular mechanics Poisson-Boltzmann surface area
      (MM-PBSA), and molecular mechanics Generalized-Born surface area (MM-GBSA)
      calculations was performed to investigate the molecular mechanism of HIV-1 IN
      vDNA interactions and the inhibition action of vDNA strand transfer inhibitor
      (INSTI) RAL. The structural analysis showed that RAL did not influence the
      interaction between vDNA and HIV-1 IN, but rather targeted a special conformation
      of HIV-1 IN to compete with host DNA and block the function of HIV-1 IN by
      forcing the 3'-OH of the terminal A17 nucleotide away from the three catalytic
      residues (Asp64, Asp116, and Glu152) and two Mg(2+) ions. Thus, the obtained
      results could be helpful for understanding of the integration process of the HIV
      1 virus and provide some new clues for the rational design and discovery of
      potential compounds that would specifically block HIV-1 virus replication.

PMID- 22144112
TI  - Glutamate released by Japanese encephalitis virus-infected microglia involves TNF
      alpha signaling and contributes to neuronal death.
AB  - The substantial activation of microglia in Japanese encephalitis virus (JEV)
      induced Japanese encephalitis found in numerous studies demonstrates that the
      disease pathogenesis involves bystander damage caused by microglia-released
      mediators. Previously, we reported that microglia synthesized and secreted
      bioactive mediators with neurotoxic potential into the cultured supernatants in
      response to JEV infection. In this study, we found that the supernatants of JEV
      infected microglia caused MK801-inhibitable neuronal damage in cultured neurons,
      indicating a potential excitotoxic mechanism. Infection with JEV was found to
      elicit the extracellular glutamate accumulation from microglia but not from
      neuron and astrocyte cultures. The glutaminase inhibitor 6-diazo-5-oxo-L
      norleucine, cystine/glutamate antiporter inhibitor alpha-aminoadipic acid, and
      the gap junction inhibitor carbenoxolone reduced JEV infection-induced microglial
      glutamate release and neurotoxicity. We further demonstrated that tumor necrosis
      factor-alpha (TNF-alpha) was a key cytokine which stimulated extensive microglial
      glutamate release by up-regulating glutaminase expression via signals involving
      protein kinase C, cAMP responsive element-binding protein, and CAAT-enhancer
      binding protein-beta. Although the elevated expression of excitatory amino acid
      transporter 1 and 2 was observed in JEV-infected cells, the glutamate uptake
      activity was significantly inhibited by TNF-alpha. The JEV infection-induced
      alterations, such as the extracellular glutamate release and glutamate-mediated
      excitoneurotoxicity, also occurred in neuron/glia cultures. Our findings support
      a potential link between neuroinflammation and the development of excitotoxic
      neuronal injury in Japanese encephalitis. The link between neuroinflammation and
      excitotoxic death may involve a mechanism in which TNF-alpha released by
      microglia plays a facilitory role in glutamate excitoneurotoxicity via up
      regulation of glutamate synthesis and down-regulation of glutamate uptake.

PMID- 22144114
TI  - Cytologic findings of a clear cell parathyroid lesion.
AB  - On fine-needle aspiration (FNA) biopsy, clear cell parathyroid lesions can be
      misdiagnosed as thyroid neoplasms, salivary gland neoplasms, paraganglioma, or
      even metastatic renal cell carcinoma. We report the clinicopathological,
      cytologic, and histologic findings of a clear cell parathyroid tumor in a 64-year
      old HIV-positive patient. A computed tomography (CT) scan with contrast showed a
      heterogeneous and enhancing mass at the inferolateral aspect of the left thyroid
      lobe. FNA showed a cellular smear with many single and loosely clustered tumor
      cells with finely granular and vacuolated light-purple cytoplasm and central
      nuclei. Occasional microfollicular structures were noted. No colloid was seen.
      This FNA was misdiagnosed as a follicular neoplasm of the thyroid. Sections of
      the excised mass showed large polyhedral cells with well-defined cell membranes
      and clear cytoplasm with a small amount of eosinophilic granular material. These
      clear cells were positive for pancytokeratin and PTH immunohistochemical stains.
      These results favored a diagnosis of parathyroid Water Clear Cell Adenoma. This
      brief report highlights the cytologic findings of clear cell parathyroid lesions
      and their potential diagnostic pitfalls.

PMID- 22144115
TI  - Downregulation of MUC1 expression and its recognition by CD8+ T cells on the
      surface of malignant pleural mesothelioma cells treated with HDACi.
AB  - Research into new treatments against malignant pleural mesothelioma (MPM) is of
      great interest, as this aggressive cancer is often resistant to conventional
      therapies. One potential strategy is the use of epigenetic drugs, such as 5-aza
      2'-deoxycytidine (5-azaCdR), a DNA-hypomethylating drug, and valproate (VPA), a
      histone deacetylase inhibitor (HDACi). Indeed, these drugs not only trigger MPM
      cell death, but also induce the expression of cancer testis antigens recognized
      by CD8(+)  T cells, such as New York-esophageal cancer-1 (NY-ESO-1). The
      objective of this study was to assess effects of these drugs on the expression
      and recognition by CD8(+)  T cells of Mucin1 (MUC1), a tumor-associated antigen
      that is overexpressed by MPM. MPM tumor cell lines were treated with epigenetic
      drugs, alone or in combination. MUC1 expression by MPM cells, and its recognition
      by a MUC1-specific CD8(+)  T-cell clone, was downregulated by HDACi when used
      alone or in combination with 5-azaCdR. This effect was not due to a blocking of
      the HLA class I presentation pathway in treated MPM cells, as NY-ESO-1 induced by
      5-azaCdR alone, or with VPA, was recognized by a NY-ESO-1-specific T-cell clone.
      This study suggests that the choice of tumor antigens could be critical for
      strategies combining epigenetic drugs with immunotherapy.

PMID- 22144116
TI  - Differences between victims of bullying and nonvictims on levels of paranoid
      ideation and persecutory symptoms, the presence of aggressive traits, the display
      of social anxiety and the recall of childhood abuse experiences in a Portuguese
      mixed clinical sample.
AB  - BACKGROUND: Bullying has been considered as a traumatic experience that can lead
      to paranoid ideation in students (Campbell and Morrison, 2007). This study aimed
      to explore differences concerning experiences of childhood trauma, the display of
      social anxiety behaviours, paranoid ideation, and aggressive traits and behaviour
      in a mixed clinical population with and without persecutory delusions, between
      individuals who reported being victims of bullying versus those who did not.
      METHOD: A total of 61 individuals with diagnoses of paranoid schizophrenia and
      social anxiety disorder were given a battery of questionnaires that measured
      bullying experiences, childhood abuse and experiences of threat and
      subordination, paranoid ideation, social anxiety behaviours, shame, and
      aggressive traits and behaviours. RESULTS: Data on the differences between the
      victims of bullying and non-victims, in terms of recalling being bullied, showed
      higher scores on childhood abuse, experiences of threat and subordination within
      the family, aggressive traits and higher display of persecutory symptoms and less
      social anxiety behaviours. CONCLUSION: Bullying is a traumatic phenomenon that is
      reported by people who suffer from persecutory delusions to a higher degree than
      those who do not. This study, thus, gives support to the idea that childhood
      abuse within the family is associated with bullying experiences and that a
      traumatic infancy may lead to the use of aggressive traits and behaviours to deal
      with a threatening environment (Bentall and Fernyhough,). This argument raises
      clinical issues regarding anger management and addressing bullying experiences in
      individuals with persecutory ideation.

PMID- 22144117
TI  - Emergence of central nervous system myeloma in the era of novel agents.
AB  - Although multiple myeloma (MM) remains an incurable disease, considerable
      improvements in survival have been made with the introduction of autologous stem
      cell transplantation and new drugs. Central nervous system (CNS) MM is a rare
      complication associated with poor survival. Historically, CNS disease developed
      early in the course of MM; however recently, patients often present with CNS
      disease following multiple lines of therapy. It is hypothesized that exposure to
      novel agents (thalidomide, lenalidomide and bortezomib) changes the natural
      history of MM, increasing the lifetime risk of CNS disease. We analysed the
      baseline characteristics, treatment and outcome data of patients who presented
      with CNS MM at Peter MacCallum Cancer Centre between 2001 and 2010. Seven
      patients were identified, from 2005 onwards. All patients were Durie-Salmon stage
      IIIA or IIIB and International Staging System Scores I to III at baseline. All
      had received at least three lines of therapy, including high-dose chemotherapy
      with autologous stem cell transplantation and a novel agent, prior to developing
      CNS MM. Median time from diagnosis to CNS disease was 24 months (range 10-42).
      All patients died after developing CNS disease with median survival post-CNS
      disease of 2 months (range 1-23). The incidence of CNS MM is increasing, and time
      to development of CNS manifestations is prolonging, associated with increased use
      of high-dose chemotherapy and novel agents. Whether this is due to improved
      overall survival or specific characteristics of these therapies is not clear.
      Despite the availability of novel agents, survival after CNS MM remains poor.

PMID- 22144118
TI  - Glycemic control in Iranian children with type 1 diabetes mellitus: effect of
      gender.
AB  - OBJECTIVES: To evaluate the effect of gender on glycemic control, diabetic
      complications and associated abnormalities in patients with type 1 diabetes
      mellitus (T1DM). METHODS: In the present cross-sectional study, patients with
      T1DM referred to endocrinology clinic in children's hospital medical center in
      Tehran from March 2005 through March 2007 were enrolled. For each patient a
      questionnaire was filled. Finally, effect of gender on glycemic control was
      analyzed. RESULTS: Male patients did self monitoring of blood glucose
      significantly more than female patients. Mean HbA1c which is used as an indicator
      of glycemic control, insulin dose per kg of body weight and also frequency of
      diabetic ketoacidosis (DKA), height problems and dyslipidemia were significantly
      higher in female patients. CONCLUSIONS: Because of worse glycemic control and
      higher incidence of DKA, dyslipidemia and height problems in female patients,
      focus on glycemic control of female patients according to local guidelines on
      clinical management of T1DM is required.

PMID- 22144119
TI  - Infantile nephrotic syndrome with microcephaly and global developmental delay:
      the Galloway Mowat Syndrome.
AB  - The authors present the first case of Galloway Mowat Syndrome (GMS), a rare
      disorder comprising of nephrotic syndrome in association with microcephaly, from
      India. An 11-mo-old girl with microcephaly, developmental delay and nystagmus
      presented with nephrotic syndrome. The perinatal and neonatal periods had been
      uneventful. The renal biopsy revealed mesangial proliferation with IgM
      deposition, while MRI of the brain showed hypomyelination. Molecular diagnosis by
      polymerase chain reaction (PCR) did not reveal any pathogenic sequences in the
      exons and the flanking intronic regions of the NPHS2 gene and LAMB2 gene. The
      infant responded to prednisolone. GMS must be suspected whenever microcephaly and
      global developmental delay occurs in association with nephrotic syndrome, as this
      is important for prognostication and genetic counseling. The genetics of GMS
      remains an enigma and further research is required to delineate the pathogenesis
      of this disorder.

PMID- 22144120
TI  - Exposure to violence and PTSD symptoms among Somali women.
AB  - Posttraumatic stress disorder (PTSD) symptoms, exposure to traumatic stressors,
      and health care utilization were examined in 84 women attending a primary health
      care clinic in Mogadishu, Somalia. The Somalia-Posttraumatic Diagnostic Scale was
      used in this active warzone to measure symptoms. Nearly all women reported high
      levels of confrontations with violence; half described being exposed to a
      potentially traumatizing event. Nearly one third had significant PTSD symptoms.
      Compared to those who did not, women who reported exposure to a traumatic
      stressor reported more confrontations with violence (7.1 vs. 3.3; p < . 001),
      health complaints (3.8 vs. 2.9; p = .03), and nearly 3 times as much (p = .03)
      health service utilization. A potentially traumatizing event was found to be a
      simplified proxy for assessing mental health distress in women attending a
      primary health care facility in highly insecure, unpredictable, resource-limited
      settings.

PMID- 22144121
TI  - Functional proteomics reveals hepatotoxicity and the molecular mechanisms of
      different forms of chromium delivered by skin administration.
AB  - Chromium compounds are known to be associated with cytotoxicity and
      carcinogenicity when applied via the skin. However, there is no perspective
      research to elucidate the causations between chromium exposure and
      hepatotoxicity. In the present study, the impact of hexavalent/trivalent chromium
      on the liver and the underlying pathogenic processes were revealed in the female
      nude mice model. The liver damage under different treatments was evaluated by
      histologic examination. Functional proteome tools combined with a network
      analysis revealed statistically significant candidate protein networks predicted
      to be changed in the presence of chromium compounds. RNA interference-mediated
      silencing and immunohistochemistry were used to confirm whether the candidate
      protein was capable of resulting in hepatotoxicity elicited by chromium.
      Potassium chromate as the Cr(VI) compound generated greater oxidative stress,
      apoptosis and hepatotoxicity compared to chromium nitrate [Cr(III)]-treated
      samples. The most meaningful changes were observed amongst proteins involved in
      carbohydrate metabolism, endoplasmic reticulum (ER) stress, calcium homeostasis
      and apoptosis. Furthermore, abrogation of transitional ER ATPase (VCP) led to
      significant inhibition in hepatic cell viability under Cr(VI) administration, and
      the expression profiles of cytokeratin were closely correlated with apoptotic
      degrees of liver tissue. Collectively, our findings suggest that Cr(VI) might
      induce the accumulation of misfolded proteins and adverse effects leading to cell
      apoptosis and liver injury. These signature networks represent an approach to
      discover novel relationships in complex data, and functional proteomics of liver
      may provide solid evidence of chromium-caused hepatic damage via the skin.

PMID- 22144123
TI  - Journal of Basic Microbiology. Editorial.

PMID- 22144124
TI  - Isolation and characterization of Klebsiella oxytoca strain degrading crude oil
      from a Tunisian off-shore oil field.
AB  - A facultatively anaerobic, Gram-negative, mesophilic, moderately halotolerant,
      non-motile, and non-sporulated bacterium, designated strain BSC5 was isolated
      from an off-shore "Sercina" oil field, located near the Kerkennah island,
      Tunisia. Yeast extract was not required for growth. Phenotypic characteristics
      and phylogenetic analysis of the 16S rRNA gene sequence of strain BSC5 revealed
      that it was related to members of the genus Klebsiella, being most closely
      related to the type strain of K. oxytoca (99% sequence similarity). Strain BSC5
      was capable of using aerobically the crude oil as substrate growth. The growth of
      strain BSC5 on crude oil was followed by measuring the OD(600 nm) and by
      enumeration of viable cells at different culture's time. GC-MS analysis showed
      that strain BSC5 was capable of degrading a wide range of aliphatic hydrocarbons
      from C(13) to C(30) . The biodegradation rate for n -alkanes reached 44% and 75%,
      after 20 and 45 days of incubation, respectively. Addition of the synthetic
      surfactant, Tween 80, accelerated the crude oil degradation. The biodegradation
      rate for n -alkanes reached 61% and 98%, after 20 and 45 days of incubation,
      respectively. Moreover, three aromatic compounds, p -hydroxybenzoate,
      protocatechuate and gentisate, were metabolized completely by strain BSC5 after
      24 h, under aerobic conditions.

PMID- 22144126
TI  - The application of immunocytochemistry to cytologic direct smears of metastatic
      merkel cell carcinoma.
AB  - Merkel cell carcinoma represents a highly aggressive cutaneous malignancy
      characterized by regional recurrences, lymph node metastases, distant metastases,
      and high mortality. As the cytomorphology of Merkel cell carcinoma can be
      mimicked by other malignancies, especially lymphoma and pulmonary small cell
      carcinoma, immunocytochemistry is often useful in confirming the diagnosis. Cell
      blocks, which are traditionally utilized for immunocytochemistry, occasionally
      exhibit insufficient cellularity. Hence, we prospectively investigated the
      application of CK20 immunocytochemistry to air-dried, unstained direct smears in
      the diagnosis of Merkel cell carcinoma fine needle aspirates (FNAs). Eight
      consecutive FNAs of Merkel cell carcinoma were prospectively examined in this
      series; seven (88%) cases exhibited immunoreactivity for CK20 in the tumor cells.
      The one CK20-negative Merkel cell carcinoma was immunoreactive for synaptophysin
      and CD56. This immunophenotype was identical to that of the original primary
      tumor. For comparison, air-dried direct smears prepared from three pulmonary
      small cell carcinoma FNAs were examined by CK20 immunocytochemistry. In all
      cases, no CK20 immunoreactivity was seen in any of the tumor cells. In
      conclusion, direct smears represent a feasible and robust source of cellular
      material for immunocytochemical studies to diagnose Merkel cell carcinoma. This
      methodology allows the cytologist to confirm on site that material for diagnostic
      immunocytochemistry is present thereby serving as a safeguard in instances where
      insufficient cell block cellularity is anticipated or encountered.

PMID- 22144127
TI  - Entropy analysis of tri-axial leg acceleration signal waveforms for measurement
      of decrease of physiological variability in human gait.
AB  - Disease-related and senescent decrease of physiological variability in biological
      time-series outputs (e.g., heart rate) has drawn increasing attention as a
      potential new type of biomarker. In this paradigm, measurement of variability in
      periodic motion may enable quantitative evaluation of functional limitation in
      people with musculoskeletal disorders. A novel technique to measure variability
      of leg motion patterns during level walking was used to study 52 adults with
      symptomatic knee osteoarthritis (OA), and 57 asymptomatic control subjects over a
      wide range of age (20-79 years). The hypothesis was that cycle-to-cycle
      variability in leg motion patterns, indexed by tri-axial acceleration signal
      entropy, would be lower in those with greater age or with knee symptoms. Leg
      motions were assessed using portable inertial monitors attached bilaterally just
      above each ankle. The tri-axial acceleration data were analyzed using a nonlinear
      variability measurement tool designated as Sample Entropy (SampEn). SampEn data
      for asymptomatic subjects exhibited a significant negative correlation (r = 
      0.287, p = 0.0306) with greater age. OA subjects had significantly lower SampEn
      values (p = 0.0002) than did age-matched asymptomatic subjects who walked at
      equivalent velocity. This approach holds promise as a basis for valid,
      inexpensive, and convenient objective evaluation of limitations in human gait
      function.

PMID- 22144128
TI  - Freehand biopsy guided by electromagnetic needle tracking: a phantom study.
AB  - PURPOSE: To evaluate the overall accuracy and time spent on biopsy guided by
      electromagnetic needle tracking in a phantom compared with the standard technique
      of US-guided biopsy with an attached steering device. Furthermore, to evaluate
      off-plane biopsy guided by needle tracking. MATERIALS AND METHODS: Three
      different series of biopsy were performed in a phantom: one with a steering
      device attached to the transducer without needle tracking, simulating the
      standard ultrasound-guided biopsy procedure (series 1), one freehand in the scan
      plane using electromagnetic needle tracking (series 2), and one freehand off-the
      scan plane using electromagnetic needle tracking (series 3). The phantom
      contained spheres of 1  cm in diameter filled with red dye. Each time of the
      phantom surface was perforated counted as an attempt. RESULTS: 180 biopsies were
      performed. The mean time spent on each biopsy in series one was 19.9 seconds (SD:
      9.1), in series two 34.1 seconds (SD: 17.9) and in series three 34.4 seconds (SD:
      14.0). The overall rate of success was: 88 % for in-plane needle-guided biopsy,
      87 % for in-plane needle tracking, and 92 % for off-plane needle tracking. No
      statistically significant difference between the methods was shown. CONCLUSION:
      Needle navigation is a potentially valuable tool for image-guided biopsy with an
      equal rate of success compared with conventional image-guided biopsy.
      Furthermore, it enables off-plane image-guided biopsy.

PMID- 22144129
TI  - 4-1BB ligand modulates direct and Rituximab-induced NK-cell reactivity in chronic
      lymphocytic leukemia.
AB  - NK cells play an important role in tumor immunosurveillance and largely
      contribute to the therapeutic success of anti-tumor antibodies like Rituximab.
      Here, we studied the role of the TNF family member 4-1BB ligand (4-1BBL) during
      the interaction of NK cells with chronic lymphocytic leukemia (CLL) cells. 4-1BBL
      was highly expressed on patient B-CLL cells in all 56 investigated cases.
      Signaling via 4-1BBL following interaction with 4-1BB, which was detected on NK
      cells of CLL patients but not healthy individuals, led to the release of
      immunoregulatory cytokines including TNF by CLL cells. CLL patient sera contained
      elevated levels of TNF and induced 4-1BB upregulation on NK cells, which in turn
      impaired direct and Rituximab-induced NK-cell reactivity against 4-1BBL
      expressing targets. NK-cell reactivity was not only enhanced by blocking the
      interaction of NK cell-expressed 4-1BB with 4-1BBL expressed by CLL cells, but
      also by preventing 4-1BB upregulation on NK cells via neutralization of TNF in
      patient serum with Infliximab. Our data indicate that 4-1BBL mediates NK-cell
      immunosubversion in CLL, and thus might contribute to the reportedly compromised
      efficacy of Rituximab to induce NK-cell reactivity in the disease, and that TNF
      neutralization may serve to enhance the efficacy of Rituximab treatment in CLL.

PMID- 22144130
TI  - Memory for target height is scaled to observer height.
AB  - According to the embodied approach to visual perception, individuals scale the
      environment to their bodies. This approach highlights the central role of the
      body for immediate, situated action. The present experiments addressed whether
      body scaling--specifically, eye-height scaling--occurs in memory when action is
      not immediate. Participants viewed standard targets that were either the same
      height as, taller than, or shorter than themselves. Participants then viewed a
      comparison target and judged whether the comparison was taller or shorter than
      the standard target. Participants were most accurate when the standard target
      height matched their own heights, taking into account postural changes.
      Participants were biased to underestimate standard target height, in general, and
      to push standard target height away from their own heights. These results are
      consistent with the literature on eye-height scaling in visual perception and
      suggest that body scaling is not only a useful metric for perception and action,
      but is also preserved in memory.

PMID- 22144131
TI  - Plasma heat shock protein 72 as a biomarker of sarcopenia in elderly people.
AB  - Sarcopenia is a geriatric syndrome in which there is a decrease of muscle mass
      and strength with aging. In age-related loss of muscle strength, there are
      numerous observations supporting the assertion that neural factors mediate muscle
      strength. A possible contributing cause may be that aging changes systemic
      extracellular heat shock protein (eHsp)72 activity. The present study was
      designed to assess the plasma levels of eHsp72 in elderly people and to
      investigate its potential interaction with components of sarcopenia. A total of
      665 men and women participated in an official medical health examination and an
      integrated health examination, including psychological and physical fitness
      tests. Blood samples were assayed for levels of plasma Hsp72, serum C-reactive
      protein, interleukin 6, tumor necrosis factor alpha, and regular biomedical
      parameters. We found that higher Hsp72 in plasma is associated with lower muscle
      mass, weaker grip strength, and slower walking speed, and may be a potential
      biomarker of sarcopenia in elderly people. This finding was supported by other
      results in the present study: (1) older age and shrinking body and lower
      hemoglobin levels, all of which characterize sarcopenia, were related to higher
      eHsp72 tertiles and (2) the ORs of the highest tertile of eHsp72 for the lowest
      tertiles of muscle mass, grip strength, and walking speed were 2.7, 2.6, and 1.8,
      respectively. These ORs were independent of age, sex, and the incidence of
      related diseases. Our results would reveal that eHsp72 in plasma is linked to
      sarcopenia factors and is a potential biomarker or predictor of sarcopenia.

PMID- 22144132
TI  - Role of a conserved aspartic acid in nucleotide binding domain 1 (NBD1) of Hsp100
      chaperones in their activities.
AB  - Besides its beneficial role in thermotolerance, the chaperone protein Hsp104 is
      involved in the inheritance of yeast Saccharomyces cerevisiae prions. Guanidine
      hydrochloride was previously shown to interfere with Hsp104 chaperone activity in
      vivo, thus impairing thermotolerance and resulting in prion curing. It was also
      reported that guanidine inhibits Hsp104 ATPase and disaggregation activity. We
      show that in vitro guanidine significantly inhibits the disaggregation activity
      of ClpB, the bacterial orthologue of Hsp104. However, guanidine exerts opposite
      effects on the ATPase activities of Hsp104 and ClpB. While the ATPase activity of
      Hsp104 is inhibited, the analogous ClpB activity is stimulated several-fold.
      Mutation of the universally conserved aspartic acid residue in position 184 to
      serine (D184S) in HSP104 and the analogous mutation in clpB (D178S) resulted in
      chaperones with lower disaggregating and ATPase activities. The activities of
      such changed chaperones are not influenced by guanidine, which suggests the role
      of this residue in the interaction with guanidine.

PMID- 22144133
TI  - Contextualizing the trauma experience of women immigrants from Central America,
      South America, and Mexico.
AB  - Trauma has been understudied among Latina immigrants from Central and South
      America. This study examined the types and context of trauma exposure experienced
      by immigrant women from Central America, South America, and Mexico living in the
      United States. Twenty-eight women seeking care in primary care or social service
      settings completed life history interviews. The majority of the women reported
      some type of trauma exposure in their countries of origin, during immigration,
      and/or in the United States. In the interviews, we identified types of trauma
      important to the experience of these immigrants that are not queried by trauma
      assessments typically used in the United States. We also identified factors that
      are likely to amplify the impact of trauma exposure. The study highlights the
      importance of utilizing a contextualized approach when assessing trauma exposure
      among immigrant women.

PMID- 22144134
TI  - Molecular characterization of Bacillus thuringiensis isolated from diverse
      habitats of India.
AB  - Bacillus thuringiensis (Bt) strains were isolated from 94 samples from different
      geographical regions. Novel types of crystalline inclusion bodies were observed
      from some of the isolates. Crystalline inclusions of bipyramidal, spherical and
      cuboidal morphology were found produced by most of the isolates. Isolate GS12
      showed crystal on one side of spore while isolate GM108 formed crystals on both
      termini of spore. Isolate GN31 produced large sized bipyramidal crystals. SDS
      PAGE analysis of the spore crystal suspension showed major protein bands in the
      range of 29 and 140 kDa. Two new serovars of Bt viz. GS4 and GN24 having H3abce
      and H3ab serotype respectively were isolated. Toxicity comparable to the
      reference strain Bacillus thuringiensis subs. kurstaki (Btk) HD-1 was observed
      for the isolates GM20, GM17 and MP3 against larvae of Helicoverpa armigera. Some
      of the isolates harboring cry genes like cry1Ac and cry2 did not show any
      toxicity towards H. armigera while most of the isolates were harboring cry1,
      cry1Ac and cry2 gene.

PMID- 22144135
TI  - Quantification of protein isoforms in mesenchymal stem cells by reductive
      dimethylation of lysines in intact proteins.
AB  - Mass spectrometry (MS)-based quantification of highly homologous proteins in
      complex samples has proven difficult due to subtle sequence variations and the
      wide dynamic range of protein isoforms present. Herein, we report the use of
      reductive dimethylation on intact proteins to quantitatively compare protein
      isoform expression in the nucleus and cytoplasm of mesenchymal stem cells (MSC)
      and normal stroma. By coupling fixed-charge MS/MS scanning, high-resolution UPLC
      FT-MS data-dependent acquisition and MASCOT-based data mining, hydrogen/deuterium
      labeled dimethyl-lysine peptides were simultaneously captured allowing the
      accurate comparison of 123 protein isoforms in parallel LC MS/MS runs. Thirty
      four isoforms were identified that had expression levels specific to MSC. Where
      possible, proteomic analyses were verified by Western blotting and were
      demonstrated to be divergent from the level of gene transcription detected for
      certain proteins. Our analysis provides a protein isoform signature specific to
      MSC and demonstrates the suitability of dimethyl-lysine labeling on intact
      proteins for quantifying highly homologous proteins on a proteome-wide scale.

PMID- 22144136
TI  - Erythropoietin augments bone formation in a rabbit posterolateral spinal fusion
      model.
AB  - We tested the hypothesis that erythropoietin (EPO) enhances bone formation after
      posterolateral spinal fusion (PLF) in a rabbit model. Thirty-four adult rabbits
      underwent posterolateral intertransverse arthrodesis at the L5-L6 level using 2.0
      g autograft per side. The animals were randomly divided into two groups receiving
      subcutaneous daily injections of either EPO or saline for 20 days. Treatment
      commenced 2 days preoperatively. Hemoglobin was monitored at baseline and 2, 4,
      and 6 weeks after fusion surgery. After euthanasia 6 weeks postoperatively,
      manual palpation, radiographic, and histomorphometric examinations were
      performed. Bone volume of the fusion mass was estimated by CT after 6 weeks. EPO
      increased bone fusion volume to 3.85 ccm (3.66-4.05) compared with 3.26 ccm (2.97
      3.55) in the control group (p<0.01). EPO treatment improved vascularization of
      the fusion mass and increased hemoglobin levels (p<0.01). Fusion rate tended to
      be higher in the EPO group based on manual palpation, CT, and radiographic
      examinations. For the first time EPO has shown to augment bone formation after
      autograft PLF in a rabbit model. Increased vascularization provides a partial
      explanation for the efficacy of EPO as a bone autograft enhancer.

PMID- 22144137
TI  - Granulation tissue associated with a ruptured epidermal inclusion cyst: a
      potential pitfall in fine needle aspirates of neck masses.

PMID- 22144138
TI  - [Evidence for the digital rectal examination in the emergency assessment of acute
      abdominal pain].
AB  - BACKGROUND: Physical examination of patients with undifferentiated abdominal pain
      (UAP) in the emergency room traditionally calls for digital rectal examination
      (DRE). Without a DRE, many textbooks deem a clinical examination incomplete. On
      the other hand, patients as well as physicians often feel uncomfortable with this
      breach of privacy involving a DRE. Especially emergency rooms do not offer an
      atmosphere where a relationship with the necessary mutual trust can be built up.
      In this light, the objective of this analysis is to assess the evidence for DRE
      via a systematic search of the relevant literature. METHODS AND RESULTS: A
      systematic search in Pubmed, Medline coupled with manual research laid the basis
      for the evaluation of relevant publications from January 1990 to March 2010.
      Keywords for the search were: "digital rectal examination" in combination with
      "acute abdominal pain", "acute abdomen" or "appendicitis". From the raw data of
      relevant publications, we extracted results into contingency tables and completed
      missing data. Above all parameters, we determined the likelihood ratios (LR) with
      corresponding 95 % confidence intervals to assess test quality. Opinions in the
      evaluated literature and many national and international textbooks diverge
      significantly on the necessity of DRE. Six studies question the significance of
      DRE when evaluating patients with undifferentiated abdominal pain and
      appendicitis, respectively. Out of these studies, five are prospective and one is
      retrospective. Overall, the diagnostic test quality of DRE was low in all studies
      with LR + in the range from 0.78 to 1.61 and LR -  from 0.91 to 1.29,
      respectively. No diagnostic relevance for DRE in combination with acute abdominal
      pain was found in these studies. Furthermore, in none of the reviewed cases did
      DRE have a relevant impact on management. CONCLUSION: The recommendation of
      generally applying DRE in the emergency room needs to be questioned critically.
      No evidence for the necessity and significance was found in the reviewed
      literature. Independently, these findings do not touch on the unequivocal
      indication of the DRE as a tool for assessing other specific conditions as well
      as screening for prostate or rectal cancer.

PMID- 22144139
TI  - [Quality assurance in colorectal cancer in Europe AD 2011].
AB  - INTRODUCTION: Malignant tumours are the second largest cause of death in Europe.
      Colorectal cancer takes second place within this group and is responsible for
      every eighth tumour-related death. CURRENT SITUATION: Surgical quality assurance
      requires a prospective observational study, any different type of study is not
      possible. A complete recording of all treated patients is a prerequisite for
      quality assurance. Currently, there are quality assurance programmes in Sweden,
      Norway, Denmark, Great Britain, Spain, Belgium, the Netherlands as well as the
      multinational study for patients from Germany, Poland and Italy. These projects
      deliver comprehensive information regarding the treatment of colorectal cancer.
      However, this information is deeply rooted in the organisation of the health-care
      system in the given country and is not easily transferable into international
      settings. Also, an interpretation of the collected data is often possible only
      within the given health-care system. FUTURE PERSPECTIVES: First, unified initial
      diagnostics is a prerequisite for quality assurance -  for the local extent and
      exclusion / confirmation of distant metastases. Until these criteria are unified,
      any comparison is limited, including a comparison of survival. Second, quality-of
      life is not recorded in any of the current projects. Third, the main focus of a
      quality assurance project must be on therapy-dependent factors. The most sensible
      method of quality control remains within the connection of preoperative
      diagnostics (estimate of a best-case scenario), the surgical technique (the
      actual result) and a standardised pathological examination (evaluation of the
      actual result). These parameters can be recorded and compared within a quality
      assurance project regardless of the limitations of the national health-care
      systems. There is no alternative to a unified diagnostics model and unified
      histopathological evaluation, a complete picture of treatment quality is also not
      possible without systematic analysis of the quality of life.

PMID- 22144140
TI  - [Spontaneous and secondary bacterial peritonitis in cirrhotic patients with
      ascites].
AB  - Peritonitis is one of the most frequent infectious complications in patients with
      liver cirrhosis and ascites. In more than 95 % it occurs as spontaneous bacterial
      peritonitis (SBP) as a result of bacterial translocation from intestinal bacteria
      and bacterial products into mesenteric lymph nodes and subsequent systemic
      circulation. Identified risk factors that justify antibiotic prophylaxis for SBP
      include a prior episode of SBP, gastrointestinal haemorrhage and low ascitic
      fluid protein in combination with renal or advanced liver failure. SBP requires
      conservative therapy, which should be empirically performed using third
      generation cephalosporins and adjunctive albumin therapy under consideration of
      individual and nosocomial risk factors for antimicrobial resistance. In contrast
      to SBP, secondary bacterial peritonitis is a rare ( < 5 % of all cases of
      peritonitis) and more unfavourable disease. It occurs as a result of hollow organ
      perforation or intra-abdominal inflammatory or ischaemic processes. Analysis of
      ascitic fluid may help substantiating the suspicion of secondary peritonitis and
      should entail a meticulous diagnostic work-up including abdominal computed
      tomography. Because of the high mortality rate (60 - 80 %) of secondary
      peritonitis antibiotic regimens with anti-anaerobic activity, prompt surgical
      treatment and interdisciplinary postoperative care are necessary to improve
      patient outcomes. 

PMID- 22144141
TI  - HLA-G inhibition of NK-cell cytolytic function is uncoupled from tumor cell lipid
      raft reorganization.
AB  - HLA-G is a non-classical HLA class I molecule with tolerogenic properties and
      restricted tissue distribution. The expression of HLA-G can be induced by tumors
      thus providing an efficient way to escape the anti-tumoral immune response.
      Although lipid rafts regulate diverse immunological mechanisms their relationship
      with HLA-G remains controversial. Our results show that HLA-G-mediated inhibition
      of both the interaction between NK and tumor cells, and of intracellular calcium
      flux in NK cells conjugated to their target cells were independent of lipid raft
      integrity. In addition, cytotoxicity assays indicated that HLA-G continued to
      efficiently inhibit NK-cell cytolytic function in several different tumor cells
      independently of lipid raft integrity. Confocal microscopy with 3D reconstruction
      combined with biochemical analysis showed that HLA-G was mainly localized outside
      the lipid rafts of tumor cells after cross-linking with specific antibody and
      remained excluded from lipid rafts during interaction with the ILT2 inhibitory
      receptor of NK cells. This study indicates that the inhibitory function of HLA-G
      is uncoupled from lipid raft organization, further distinguishing HLA-G from
      classical HLA molecules and providing novel information in the understanding of
      tumor immune escape mechanism mediated through HLA-G.

PMID- 22144143
TI  - Long-term functional adeno-associated virus-microdystrophin expression in the
      dystrophic CXMDj dog.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe, inherited, muscle
      wasting disorder caused by mutations in the dystrophin gene. Preclinical studies
      of adeno-associated virus gene therapy for DMD have been described in mouse and
      dog models of this disease. However, low and transient expression of
      microdystrophin in dystrophic dogs and a lack of long-term microdystrophin
      expression associated with a CD8(+)  T-cell response in DMD patients suggests
      that the development of improved microdystrophin genes and delivery strategies is
      essential for successful clinical trials in DMD patients. METHODS: We have
      previously shown the efficiency of mRNA sequence optimization of mouse
      microdystrophin in ameliorating the pathology of dystrophic mdx mice. In the
      present study, we generated adeno-associated virus (AAV)2/8 vectors expressing an
      mRNA sequence-optimized canine microdystrophin under the control of a muscle
      specific promoter and injected intramuscularly into a single canine X-linked
      muscular dystrophy (CXMDj) dog. RESULTS: Expression of stable and high levels of
      microdystrophin was observed along with an association of the dystrophin
      associated protein complex in intramuscularly injected muscles of a CXMDj dog for
      at least 8 weeks without immune responses. Treated muscles were highly protected
      from dystrophic damage, with reduced levels of myofiber permeability and central
      nucleation. CONCLUSIONS: The data obtained in the present study suggest that the
      use of canine-specific and mRNA sequence-optimized microdystrophin genes in
      conjunction with a muscle-specific promoter results in high and stable levels of
      microdystrophin expression in a canine model of DMD. This approach will
      potentially allow the reduction of dosage and contribute towards the development
      of a safe and effective AAV gene therapy clinical trial protocol for DMD.

PMID- 22144142
TI  - Age-related differences in diffusion model boundary optimality with both trial
      limited and time-limited tasks.
AB  - In two-choice decision tasks, Starns and Ratcliff (Psychology and Aging 25: 377
      390, 2010) showed that older adults are farther from the optimal speed-accuracy
      trade-off than young adults. They suggested that the age effect resulted from
      differences in task goals, with young participants focused on balancing speed and
      accuracy and older participants focused on minimizing errors. We compared speed
      accuracy criteria with a standard procedure (blocks that had a fixed numbers of
      trials) to a condition in which blocks lasted a fixed amount of time and
      participants were instructed to get as many correct responses as possible within
      the time limit-a goal that explicitly required balancing speed and accuracy. Fits
      of the diffusion model showed that criteria differences persisted in the fixed
      time condition, suggesting that age differences are not solely based on
      differences in task goals. Also, both groups produced more conservative criteria
      in difficult conditions when it would have been optimal to be more liberal.

PMID- 22144144
TI  - Postcombat outcomes among Marines with preexisting mental diagnoses.
AB  - Preexisting mental disorders are not always considered in mental health studies
      with military populations, even though prior diagnoses may be a risk factor for
      additional psychiatric harm stemming from combat exposure, as well as
      postdeployment behavioral problems. The objectives of this study were to
      investigate postcombat psychiatric and career outcomes among Marines with
      preexisting mental disorder diagnoses who deployed to combat in Iraq,
      Afghanistan, or Kuwait from 2002 to 2008. Marines with a preexisting diagnosis
      were 3.6 times (p < .001) more likely to have at least 1 postdeployment mental
      health disorder within 6 months postdeployment compared with Marines with no
      prior psychiatric diagnoses. Marines with a preexisting diagnosis were also 1.8
      (p < .001) times more likely to receive a new-onset psychiatric diagnosis within
      6 months postdeployment, indicating that postdeployment mental health concerns in
      this cohort extend beyond continuation of earlier disorders. Additionally,
      demotions and separation were significantly associated with having any
      preexisting mental health diagnoses (yielding odds ratios of 2.34 and 2.00, p <
      .001, respectively. Based on the current findings, it may be advisable to mandate
      a full medical and psychiatric record review during deployment health screening
      as part of new initiatives to address whether combat exposure has worsened
      preexisting conditions or compounded them with new-onset concerns.

PMID- 22144145
TI  - Bacterial molecular networks: bridging the gap between functional genomics and
      dynamical modelling.
AB  - This introductory review synthesizes the contents of the volume Bacterial
      Molecular Networks of the series Methods in Molecular Biology. This volume
      gathers 9 reviews and 16 method chapters describing computational protocols for
      the analysis of metabolic pathways, protein interaction networks, and regulatory
      networks. Each protocol is documented by concrete case studies dedicated to model
      bacteria or interacting populations. Altogether, the chapters provide a
      representative overview of state-of-the-art methods for data integration and
      retrieval, network visualization, graph analysis, and dynamical modelling.

PMID- 22144146
TI  - Bacterial interactomes: from interactions to networks.
AB  - In order to ensure their function(s) in the cell, proteins are organized in
      machineries, underlaid by a complex network of interactions. Identifying protein
      interactions is thus crucial to our understanding of cell functioning. Technical
      advances in molecular biology and genomic technology now allow for the systematic
      study of the interactions occurring in a given organism. This review first
      presents the techniques readily available to microbiologists for studying protein
      protein interactions in bacteria, as well as their usability for high-throughput
      studies. Two types of techniques need to be considered: (1) the isolation of
      protein complexes from the organism of interest by affinity purification, and
      subsequent identification of the complex partners by mass spectrometry and (2)
      two-hybrid techniques, in general based on the production of two recombinant
      proteins whose interaction has to be tested in a reporter cell. Next, we
      summarize the bacterial interactomes already published. Finally, the strengths
      and pitfalls of the techniques are discussed, together with the potential
      prospect of interactome studies in bacteria.

PMID- 22144147
TI  - From bacterial to microbial ecosystems (metagenomics).
AB  - Metagenomics is revolutionizing the field of microbial ecology through techniques
      that eliminate the prerequisite of culturing. Metagenomic studies of microbial
      populations in different environments reveal the incredible diversity and
      adaptive capabilities of these organisms. With the advent of cheaper, high
      throughput sequencing technologies, these studies are also producing vast amounts
      of sequence data. Here, we discuss the different components of a metagenomic
      study including sample collection, DNA extraction, sequencing, and informatics.
      We highlight their issues and challenges, and review the solutions that are
      currently in use. We conclude with examples of metagenomic studies conducted on
      environments of varying complexities.

PMID- 22144148
TI  - Prokaryote genome fluidity: toward a system approach of the mobilome.
AB  - The importance of horizontal/lateral gene transfer (LGT) in shaping the genomes
      of prokaryotic organisms has been recognized in recent years as a result of
      analysis of the increasing number of available genome sequences. LGT is largely
      due to the transfer and recombination activities of mobile genetic elements
      (MGEs). Bacterial and archaeal genomes are mosaics of vertically and horizontally
      transmitted DNA segments. This generates reticulate relationships between members
      of the prokaryotic world that are better represented by networks than by
      "classical" phylogenetic trees. In this review we summarize the nature and
      activities of MGEs, and the problems that presently limit their analysis on a
      large scale. We propose routes to improve their annotation in the flow of genomic
      and metagenomic sequences that currently exist and those that become available.
      We describe network analysis of evolutionary relationships among some MGE
      categories and sketch out possible developments of this type of approach to get
      more insight into the role of the mobilome in bacterial adaptation and evolution.

PMID- 22144149
TI  - Reticulate classification of mosaic microbial genomes using NeAT website.
AB  - The tree of life is the classical representation of the evolutionary
      relationships between existent species. A tree is appropriate to display the
      divergence of species through mutation, i.e., by vertical descent. However,
      lateral gene transfer (LGT) is excluded from such representations. When LGT
      contribution to genome evolution cannot be neglected (e.g., for prokaryotes and
      mobile genetic elements), the tree becomes misleading. Networks appear as an
      intuitive way to represent both vertical and horizontal relationships, while
      overlapping groups within such graphs are more suitable for their classification.
      Here, we describe a method to represent both vertical and horizontal
      relationships. We start with a set of genomes whose coded proteins have been
      grouped into families based on sequence similarity. Next, all pairs of genomes
      are compared, counting the number of proteins classified into the same family.
      From this comparison, we derive a weighted graph where genomes with a significant
      number of similar proteins are linked. Finally, we apply a two-step clustering of
      this graph to produce a classification where nodes can be assigned to multiple
      clusters. The procedure can be performed using the Network Analysis Tools (NeAT)
      website.

PMID- 22144150
TI  - From metabolic reactions to networks and pathways.
AB  - Enzymatic reactions form a hypergraph structure and their translation into a
      graph structure accompanies an information loss. This chapter introduces well
      known topological transformations from metabolic reactions to a graph, and
      discusses their advantages and disadvantages. Also discussed is the legitimacy of
      defining cofactors or currency metabolites, and suitable application area of each
      representation.

PMID- 22144151
TI  - Predicting metabolic pathways by sub-network extraction.
AB  - Various methods result in groups of functionally related genes obtained from
      genomes (operons, regulons, syntheny groups, and phylogenetic profiles),
      transcriptomes (co-expression groups) and proteomes (modules of interacting
      proteins). When such groups contain two or more enzyme-coding genes, graph
      analysis methods can be applied to extract a metabolic pathway that interconnects
      them. We describe here the way to use the Pathway extraction tool available on
      the NeAT Web server ( http://rsat.ulb.ac.be/neat/ ) to piece together the
      metabolic pathway from a group of associated, enzyme-coding genes. The tool
      identifies the reactions that can be catalyzed by the products of the query genes
      (seed reactions), and applies sub-graph extraction algorithms to extract from a
      metabolic network a sub-network that connects the seed reactions. This sub
      network represents the predicted metabolic pathway. We describe here the pathway
      prediction process in a step-by-step way, give hints about the main parametric
      choices, and illustrate how this tool can be used to extract metabolic pathways
      from bacterial genomes, on the basis of two study cases: the isoleucine-valine
      operon in Escherichia coli and a predicted operon in Cupriavidus (Ralstonia)
      metallidurans.

PMID- 22144152
TI  - Directed module detection in a large-scale expression compendium.
AB  - Public online microarray databases contain tremendous amounts of expression data.
      Mining these data sources can provide a wealth of information on the underlying
      transcriptional networks. In this chapter, we illustrate how the web services
      COLOMBOS and DISTILLER can be used to identify condition-dependent coexpression
      modules by exploring compendia of public expression data. COLOMBOS is designed
      for user-specified query-driven analysis, whereas DISTILLER generates a global
      regulatory network overview. The user is guided through both web services by
      means of a case study in which condition-dependent coexpression modules
      comprising a gene of interest (i.e., "directed") are identified.

PMID- 22144153
TI  - Using phylogenetic profiles to predict functional relationships.
AB  - Phylogenetic profiling involves the comparison of phylogenetic data across gene
      families. It is possible to construct phylogenetic trees, or related data
      structures, for specific gene families using a wide variety of tools and
      approaches. Phylogenetic profiling involves the comparison of this data to
      determine which families have correlated or coupled evolution. The underlying
      assumption is that in certain cases these couplings may allow us to infer that
      the two families are functionally related: that is their function in the cell is
      coupled. Although this technique can be applied to noncoding genes, it is more
      commonly used to assess the function of protein coding genes. Examples of
      proteins that are functionally related include subunits of protein complexes, or
      enzymes that perform consecutive steps along biochemical pathways. We hypothesize
      the deletion of one of the families from a genome would then indirectly affect
      the function of the other. Dozens of different implementations of the
      phylogenetic profiling technique have been developed over the past decade. These
      range from the first simple approaches that describe phylogenetic profiles as
      binary vectors to the most complex ones that attempt to model to the coevolution
      of protein families on a phylogenetic tree. We discuss a set of these
      implementations and present the software and databases that are available to
      perform phylogenetic profiling.

PMID- 22144154
TI  - Extracting regulatory networks of Escherichia coli from RegulonDB.
AB  - RegulonDB contains the largest and currently best-known data set on
      transcriptional regulation in a single free-living organism, that of Escherichia
      coli K-12 (Gama-Castro et al. Nucleic Acids Res 36:D120-D124, 2008). This
      organized knowledge has been the gold standard for the implementation of
      bioinformatic predictive methods on gene regulation in bacteria (Collado-Vides et
      al. J Bacteriol 191:23-31, 2009). Given the complexity of different types of
      interactions, the difficulty of visualizing in a single figure of the whole
      network, and the different uses of this knowledge, we are making available
      different views of the genetic network. This chapter describes case studies about
      how to access these views, via precomputed files, web services and SQL, including
      sigma-gene relationships corresponding to transcription of alternative RNA
      polymerase holoenzyme promoters; as well as, transcription factor (TF)-genes, TF
      operons, TF-TF, and TF-regulon interactions. 17.

PMID- 22144155
TI  - Browsing metabolic and regulatory networks with BioCyc.
AB  - The BioCyc database collection at BioCyc.org integrates genome and cellular
      network information for more than 1,100 organisms. This method chapter describes
      Web-based tools for browsing metabolic and regulatory networks within BioCyc.
      These tools allow visualization of complete metabolic and regulatory networks,
      and allow the user to zoom-in on regions of the network of interest. The user can
      find objects of interest such as genes and metabolites within the networks, and
      can selectively examine the connectivity of the network. The EcoCyc database
      within the BioCyc collection has been extensively curated. The descriptions
      within EcoCyc of the Escherichia coli metabolic network and regulatory network
      were derived from thousands of publications. Other BioCyc databases received
      moderate levels of curation, or no curation at all. Those databases receiving no
      curation contain metabolic networks that were computationally inferred from the
      annotated genome sequences of each organism.

PMID- 22144156
TI  - Algorithms for systematic identification of small subgraphs.
AB  - The ability to analyze large biological networks proves to be a computationally
      expensive task, but the information one can gain is worth the cost and effort. In
      cancer research for example, one is able to derive knowledge about putative drug
      targets by revealing the strengths and weaknesses inherent in a protein-protein
      interaction (PPI) network. Further, network analyses can be used to optimize high
      throughput genetic and proteomic experiments. In addition, the study of
      biological networks is now an active part of molecular biology. In this chapter,
      we review techniques for studying biological networks in general but with a focus
      on PPI networks, including an example of a bacterial PPI network. After a brief
      introduction, we concentrate on methods based on the analysis of subnetworks,
      namely, graph motifs and graphlets.

PMID- 22144157
TI  - The degree distribution of networks: statistical model selection.
AB  - The degree distribution has been viewed as an important characteristic of network
      data. Many biological networks have been labelled scale-free as their degree
      distribution can be approximately described by a power-law probability
      distribution. This chapter presents a formal statistical model selection
      procedure that can determine which functional form, from a collection of
      specified models, best describes the degree distribution of network data. The
      degree distribution found for empirical data is viewed as belonging to a class of
      probability models and the model which best describes the data is determined in a
      maximum likelihood framework. In conclusion, it is important to note that these
      statistical tests do not confirm the true underlying distribution of the observed
      data, but instead show which models from a chosen set best describe the data. In
      reality, these approaches should be viewed as providing evidence for which
      probability models do not adequately (or optimally) describe the data, and give
      an indication of the underlying sampling and true interaction properties of the
      system considered.

PMID- 22144158
TI  - MAVisto: a tool for biological network motif analysis.
AB  - Data from high-throughput experimental methods are currently being used to
      construct complex biological networks. These include regulatory gene networks,
      regulatory protein-DNA networks, protein-protein interaction networks, or
      metabolic networks. Independent of its type, every network can be characterized
      by a number of parameters such as number of nodes, number of edges connecting
      nodes, direction and weight of edges, in- and out-degree of nodes, etc. One can
      draw an analogy of such rather simple network parameters to the primary sequence
      of proteins or nucleic acids. More insight can be gained by an analysis of the
      secondary and tertiary structure of biomolecules, which often contain motifs. The
      same holds for biological networks. The occurrence and frequency of certain
      motifs or pattern characterize the topology and often the functional space of a
      network. Here, we describe the utilization of the free software MAVisto, which
      was designed to mine networks for typical motifs by combining a flexible motif
      search algorithm with interactive exploration methods and sophisticated
      visualization techniques.

PMID- 22144159
TI  - Using MCL to extract clusters from networks.
AB  - MCL is a general purpose cluster algorithm for both weighted and unweighted
      networks. The algorithm utilises network topology as well as edge weights, is
      highly scalable and has been applied in a wide variety of bioinformatic methods.
      In this chapter, we give protocols and case studies for clustering of networks
      derived from, respectively, protein sequence similarities and gene expression
      profile correlations.

PMID- 22144160
TI  - Protein complex prediction with RNSC.
AB  - Graph theory analysis of biological networks, such as protein-protein
      interactions (PPIs), gene regulatory, metabolic, etc., has identified a strong
      relationship between topology of these networks and the underlying cellular
      function and biological processes (Sharan et al. Mol Syst Biol 3:88, 2007). We
      focus on PPI networks, in which nodes correspond to proteins and edges represent
      interactions among the proteins. The size of these networks is ever growing, and
      thus efficient identification of various network motifs and dense sub-networks
      has become necessary. Predicting highly connected sub-graphs in a PPI network is
      important to biologists as it may help to identify biologically meaningful
      protein complexes, and with further integrative analysis may lead to identifying
      dynamic assembly of individual subunits in these complexes. In this chapter, we
      describe one method for predicting protein complexes in two steps. The first step
      is to partition the nodes of a PPI network (i.e. proteins) into highly connected
      groups or clusters using the Restricted Neighbourhood Search Clustering
      algorithm. This provides a set of clusters that represent candidate complexes.
      The second step of the method is to filter the candidate complexes based on three
      criteria: minimum cluster size, minimum interaction density, and minimum
      functional homogeneity, which reflects the extent to which the proteins of the
      candidate cluster operate in the same functional group. Candidate complexes
      passing all three criteria are then put forward as predicted protein complexes.
      The effectiveness of this method is investigated in the previous studies (King et
      al. Bioinformatics 20:3013-3020, 2004; Brohee and van Helden BMC Bioinformatics
      7:488, 2006; and Moschopoulos et al. BMC Bioinformatics 10(Suppl 6):S11, 2009).

PMID- 22144161
TI  - Network analysis and protein function prediction with the PRODISTIN Web site.
AB  - Interactions between macromolecules are deciphered to gain information about
      biological processes and protein function. This information is hidden in large
      interaction networks, yet very complicated to dissect. In this context, the
      PRODISTIN Web site is dedicated to the clustering of network proteins according
      to the identity of their interaction partners, and to the subsequent functional
      annotation of these clusters. It allows analysing functionally networks and
      eventually leads to the prediction of function for uncharacterized protein based
      on their belonging to protein clusters. PRODISTIN analyses also provide an
      overview of the different biological processes existing in a given interactome.
      Here, we present a step-by-step procedure to analyse interaction networks using
      the PRODISTIN Web site. The protocol is illustrated by an application to the
      Campylobacter jejuni interactome.

PMID- 22144162
TI  - Using the NeAT toolbox to compare networks to networks, clusters to clusters, and
      network to clusters.
AB  - In this chapter, we present and interpret some operations on biological networks
      that can easily performed with NeAT, a set of Web tools aimed at studying
      biological networks (or graphs) and classifications. These approaches are of
      particular interest for biologists and scientists who need to assess the
      reliability of new datasets (either experimental or predicted) by comparing them
      to established references. Firstly, we describe the steps that will allow a
      nonspecialist user to compare two networks to compute their union and the
      statistical significance of their intersection. Next, we show how to map
      functional classes (e.g., GO categories, sets of regulons or complexes) onto a
      biological network. A third protocol explains how to compare two sets of
      functional classes, e.g., to assess statistically the biological relevance of
      some computationally returned groups of genes (clustering). The metrics as well
      as the results obtained by following the different protocols are extensively
      described and explained. NeAT is available at the following URL:
      http://rsat.bigre.ulb.ac.be/rsat/index_neat.html.

PMID- 22144163
TI  - Analyzing biological data using R: methods for graphs and networks.
AB  - R is a powerful language and widely used software tool for the analysis and
      visualization of data. Its core capabilities can be extended through many
      different add-on packages. Among the many packages are some which offer a broad
      range of facilities for analyzing statistical properties of graphs. This chapter
      provides a practical tutorial covering the use of R methods for graphs and
      networks to examine biological data and analyze their topological and statistical
      properties.

PMID- 22144164
TI  - Detecting structural invariants in biological reaction networks.
AB  - The detection and analysis of structural invariants in cellular reaction networks
      is of central importance to achieve a more comprehensive understanding of
      metabolism. In this work, we review different kinds of structural invariants in
      reaction networks and their Petri net-based representation. In particular, we
      discuss invariants that can be obtained from the left and right null spaces of
      the stoichiometric matrix which correspond to conserved moieties (P-invariants)
      and elementary flux modes (EFMs, minimal T-invariants). While conserved moieties
      can be used to detect stoichiometric inconsistencies in reaction networks, EFMs
      correspond to a mathematically rigorous definition of the concept of a
      biochemical pathway. As outlined here, EFMs allow to devise strategies for strain
      improvement, to assess the robustness of metabolic networks subject to
      perturbations, and to analyze the information flow in regulatory and signaling
      networks. Another important aspect addressed by this review is the limitation of
      metabolic pathway analysis using EFMs to small or medium-scale reaction networks.
      We discuss two recently introduced approaches to circumvent these limitations.
      The first is an algorithm to enumerate a subset of EFMs in genome-scale metabolic
      networks starting from the EFM with the least number of reactions. The second
      approach, elementary flux pattern analysis, allows to analyze pathways through
      specific subsystems of genome-scale metabolic networks. In contrast to EFMs,
      elementary flux patterns much more accurately reflect the metabolic capabilities
      of a subsystem of metabolism as well as its integration into the entire system.

PMID- 22144165
TI  - Petri nets in Snoopy: a unifying framework for the graphical display,
      computational modelling, and simulation of bacterial regulatory networks.
AB  - Using the example of phosphate regulation in enteric bacteria, we demonstrate the
      particular suitability of stochastic Petri nets to model biochemical phenomena
      and their simulative exploration by various features of the software tool Snoopy.

PMID- 22144166
TI  - Genetic network analyzer: a tool for the qualitative modeling and simulation of
      bacterial regulatory networks.
AB  - Genetic Network Analyzer (GNA) is a tool for the qualitative modeling and
      simulation of gene regulatory networks, based on so-called piecewise-linear
      differential equation models. We describe the use of this tool in the context of
      the modeling of bacterial regulatory networks, notably the network of global
      regulators controlling the adaptation of Escherichia coli to carbon starvation
      conditions. We show how the modeler, by means of GNA, can define a regulatory
      network, build a model of the network, determine the steady states of the system,
      perform a qualitative simulation of the network dynamics, and analyze the
      simulation results using model-checking tools. The example illustrates the
      interest of qualitative approaches for the analysis of the dynamics of bacterial
      regulatory networks.

PMID- 22144167
TI  - Logical modelling of gene regulatory networks with GINsim.
AB  - Discrete mathematical formalisms are well adapted to model large biological
      networks, for which detailed kinetic data are scarce. This chapter introduces the
      reader to a well-established qualitative (logical) framework for the modelling of
      regulatory networks. Relying on GINsim, a software implementing this logical
      formalism, we guide the reader step by step towards the definition and the
      analysis of a simple model of the lysis-lysogeny decision in the bacteriophage
      lambda.

PMID- 22144168
TI  - Modelling the evolution of mutualistic symbioses.
AB  - Mutualistic microbial symbioses are one of the key innovations in the evolution
      of biological diversity, enabling the expansion of species' niches and the
      production of sophisticated structures such as the eukaryotic cell. For some of
      the best-studied cases, we are beginning to have network models of symbiotic
      metabolism, but this work is in its infancy and has not been developed with an
      evolutionary perspective. However, theoreticians have long been interested in how
      these symbioses arise and persist and have applied modelling approaches from
      economics, evolution, ecology, and sociobology to a number of fundamental
      questions. We provide an overview of these questions, followed by specific
      modelling examples. We cover economic game theory, including the Prisoner's
      Dilemma, the Snowdrift game, and biological markets. We also describe the eco
      evolutionary framework of adaptive dynamics, inclusive fitness, and population
      genetic models. We aim to provide insight into the strengths and weaknesses of
      each approach and into how current evolutionary methods can benefit an
      understanding of the mechanistic basis of host-symbiont interactions elucidated
      by molecular network models.

PMID- 22144169
TI  - Modelling the onset of virulence in pathogenic bacteria.
AB  - Bacterial virulence is a multifactorial process. In this chapter, we review some
      known mechanisms used by bacteria to trigger their production of virulence
      factors. We develop the idea that although the onset of virulence shows up an
      abrupt transition, the modelling of this dynamics can be classified in two
      qualitatively distinct infectious transitions which are respectively called
      "shift" or "switch." We review methods enabling one to determine the types of
      behaviour that can be exhibited by a given model and we consider applications in
      three cases of virulence factor regulation. We conclude that in most cases a
      "successful" infection would require that the onset of virulence follows an
      irreversible switch behaviour.

PMID- 22144170
TI  - Spatial and stochastic cellular modeling with the Smoldyn simulator.
AB  - This chapter describes how to use Smoldyn, which is a computer program for
      modeling cellular systems with spatial and stochastic detail. Smoldyn represents
      each molecule of interest as an individual point-like particle. These simulated
      molecules diffuse, interact with surfaces (e.g., biological membranes), and
      undergo chemical reactions much as they would in real biochemical systems.
      Smoldyn has been used to model signal transduction within bacterial cells,
      pheromone signaling between yeast cells, bacterial carboxysome function,
      diffusion in crowded spaces, and many other systems. A new "rule-based modeling"
      feature automatically generates chemical species and reactions as they arise in
      simulations due to protein modifications and complexation. Smoldyn is easy to
      use, quantitatively accurate, and computationally efficient. It is generally best
      for systems with length scales between nanometers and several microns, time
      scales from tens of nanoseconds to tens of minutes, and up to about 10(5)
      individual molecules. Smoldyn runs on Macintosh, Linux, or Windows systems, is
      open source, and can be downloaded from http://www.smoldyn.org.

PMID- 22144171
TI  - Correction of systematic errors in quantitative proton density mapping.
AB  - Interest in techniques yielding quantitative information about brain tissue
      proton densities is increasing. In general, all parameters influencing the signal
      amplitude are mapped in several acquisitions and then eliminated from the image
      data to obtain pure proton density weighting. Particularly, the measurement of
      the receiver coil sensitivity profile is problematic. Several methods published
      so far are based on the reciprocity theorem, assuming that receive and transmit
      sensitivities are identical. Goals of this study were (1) to determine
      quantitative proton density maps using an optimized variable flip angle method
      for T(1) mapping at 3 T, (2) to investigate if systematic errors can arise from
      insufficient spoiling of transverse magnetization, and (3) to compare two methods
      for mapping the receiver coil sensitivity, based on either the reciprocity
      theorem or bias field correction. Results show that insufficient spoiling yields
      systematic errors in absolute proton density of about 3-4 pu. A correction
      algorithm is proposed. It is shown that receiver coil sensitivity mapping based
      on the reciprocity theorem yields erroneous proton density values, whereas
      reliable data are obtained with bias field correction. Absolute proton density
      values in different brain areas, evaluated on six healthy subjects, are in
      excellent agreement with recent literature results.

PMID- 22144172
TI  - Nutrigenomics of hepatic steatosis in a feline model: effect of monosodium
      glutamate, fructose, and Trans-fat feeding.
AB  - Nonalcoholic fatty liver disease begins with a relatively benign hepatic
      steatosis, often associated with increased adiposity, but may progress to a more
      severe nonalcoholic steatohepatitis with inflammation. A subset of these patients
      develops progressive fibrosis and ultimately cirrhosis. Various dietary
      components have been shown to contribute to the development of liver disease,
      including fat, sugars, and neonatal treatment with high doses of monosodium
      glutamate (MSG). However, rodent models of progressive disease have been
      disappointing, and alternative animal models of diet-induced liver disease would
      be desirable, particularly if they contribute to our knowledge of changes in gene
      expression as a result of dietary manipulation. The domestic cat has previously
      been shown to be an appropriate model for examining metabolic changes-associated
      human diseases such as diabetes. Our aim was therefore to compare changes in
      hepatic gene expression induced by dietary MSG, with that of a diet containing
      Trans-fat and high fructose corn syrup (HFCS), using a feline model. MSG
      treatment increased adiposity and promoted hepatic steatosis compared to control
      (P < 0.05). Exposure to Trans-fat and HFCS promoted hepatic fibrosis and markers
      of liver dysfunction. Affymetrix microarray analysis of hepatic gene expression
      showed that dietary MSG promoted the expression of genes involved in cholesterol
      and steroid metabolism. Conversely, Trans-fat and HFCS feeding promoted the
      expression of genes involved in lipolysis, glycolysis, liver damage/regeneration,
      and fibrosis. Our feline model examining gene-diet interactions (nutrigenomics)
      demonstrates how dietary MSG, Trans-fat, and HFCS may contribute to the
      development of hepatic steatosis.

PMID- 22144173
TI  - Inter-organ proteomic analysis reveals insights into the molecular mechanisms
      underlying the anti-diabetic effects of cis-9, trans-11-conjugated linoleic acid
      in ob/ob mice.
AB  - cis-9, trans-11-Conjugated linoleic acid (c9 t11 CLA) exerts anti-diabetic
      effects by improving systemic insulin sensitivity and inflammation. Levels of CLA
      in beef can be increased by feeding cattle on pasture. This study aimed to
      explore the efficacy of a CLA-rich diet (0.6% w/w c9 t11 CLA), presented as beef
      enriched with CLA or beef supplemented with synthetic CLA (c9 t11 CLA), for 28
      days on molecular biomarkers of the metabolic syndrome, and adipose, hepatic, and
      skeletal muscle proteome in male ob/ob mice. Despite equal weight gain, CLA-fed
      mice had lower plasma glucose, insulin, non-esterified fatty acid,
      triacylglycerol and interleukin-6, and higher adiponectin concentrations than
      controls. c9 t11 CLA induced differential regulation of redox status across all
      tissues, and decreased hepatic and muscle endoplasmic reticulum stress. CLA also
      modulated mechanistic links between the actin cytoskeleton, insulin signalling,
      glucose transport and inflammation in the adipose tissue. In the liver and
      muscle, c9 t11 CLA improved metabolic flexibility through co-ordination between
      carbohydrate and energy metabolism. c9 t11 CLA may ameliorate systemic insulin
      sensitivity in obesity-induced diabetes by altering cellular stress and redox
      status, and modulating nutrient handling in key insulin-sensitive tissues through
      complex biochemical interplay among representative proteomic signatures.

PMID- 22144174
TI  - Isolation and characterization of an acrylamide-degrading yeast Rhodotorula sp.
      strain MBH23 KCTC 11960BP.
AB  - As well as for chemical and environmental reasons, acrylamide is widely used in
      many industrial applications. Due to its carcinogenicity and toxicity, its
      discharge into the environment causes adverse effects on humans and ecology
      alike. In this study, a novel acrylamide-degrading yeast has been isolated. The
      isolate was identified as Rhodotorula sp. strain MBH23 using ITS rRNA analysis.
      The results showed that the best carbon source for growth was glucose at 1.0%
      (w/v). The optimum acrylamide concentration, being a nitrogen source for cellular
      growth, was at 500 mg l(-1). The highest tolerable concentration of acrylamide
      was 1500 mg l(-1) whereas growth was completely inhibited at 2000 mg l(-1). At
      500 mg l(-1), the strain MBH completely degraded acrylamide on day 5. Acrylic
      acid as a metabolite was detected in the media. Strain MBH23 grew well between pH
      6.0 and 8.0 and between 27 and 30  degrees C. Amides such as 2-chloroacetamide,
      methacrylamide, nicotinamide, acrylamide, acetamide, and propionamide supported
      growth. Toxic heavy metals such as mercury, chromium, and cadmium inhibited
      growth on acrylamide.

PMID- 22144175
TI  - Cytopathologic characteristics of the primary strumal carcinoid tumor of the
      ovary: a case report with emphasis on differential diagnostic considerations.
AB  - Primary strumal carcinoid tumor of the ovary (SCTO) is an extremely rare entity,
      though the survival rate is excellent if the disease is confined to one ovary. A
      case is presented here in which intraoperative squash smears in a 45-year-old
      woman with a left adnexal mass revealed dispersed or small clusters of neoplastic
      cells forming loosely cohesive gland-like structures with abundant cytoplasm. The
      nuclear chromatin was finely granular with a "salt and pepper" appearance and
      occasional tiny nucleoli. The position of the nucleus presented a vaguely
      plasmacytoid appearance. Small fragments of thyroidal colloid-like structures
      were also identified. A cytopathologic diagnosis of a SCTO was suggested. Further
      evaluation and immunohistochemical studies were conducted on formalin-fixed,
      paraffin-embedded material. Cords or nests of uniform cells with abundant
      cytoplasm, and eccentric nuclei with coarse chromatin and occasional colloidal
      tissue were identified on H&E sections. The tumor cells showed diffuse and strong
      cytoplasmic staining for chromogranin A, synaptophysin, CD56, and vimentin but
      were negative for calretinin, alpha-inhibin or CDX2. The proliferative index with
      MIB-1 was around 3%. Thyroidal colloid-like structures were immunoreactive for
      thyroglobulin and TTF-1 stains. The diagnosis of primary SCTO was confirmed based
      on cytopathologic, histopathological, and immunohistochemical results, and the
      location of the tumor. Awareness of the cytopathological findings of SCTO can
      assist in diagnosing this rare entity correctly.

PMID- 22144176
TI  - Reduced tumor-antigen density leads to PD-1/PD-L1-mediated impairment of
      partially exhausted CD8+ T cells.
AB  - Clinical progression of cancer patients is often observed despite the presence of
      tumor-reactive T cells. Co-inhibitory ligands of the B7 superfamily have been
      postulated to play a part in this tumor-immune escape. One of these molecules, PD
      L1 (B7-H1, CD274), is widely expressed on tumor cells and has been shown to
      mediate T-cell inhibition. However, attempts to correlate PD-L1 tumor expression
      with negative prognosis have been conflicting. To better understand when PD-1/PD
      L1-mediated inhibition contributes to the functional impairment of tumor-specific
      CD8(+)  T cells, we varied the levels of antigen density and/or PD-L1 expression
      at the surface of tumor cells and exposed them to CD8(+)  T cells at different
      levels of functional exhaustion. We found that the gradual reduction of cognate
      antigen expression by PD-L1-expressing tumor cells increased the susceptibility
      of partially exhausted T cells to PD-1/PD-L1-mediated inhibition in vitro as well
      as in vivo. In conclusion, chronically stimulated CD8(+)  T cells become
      sensitive to PD-1/PD-L1-mediated functional inhibition upon low antigen
      detection; a setting which is likely involved during tumor-immune escape.

PMID- 22144177
TI  - Prediction of a ligand-binding niche within a human olfactory receptor by
      combining site-directed mutagenesis with dynamic homology modeling.

PMID- 22144178
TI  - KLF9 is a novel transcriptional regulator of bortezomib- and LBH589-induced
      apoptosis in multiple myeloma cells.
AB  - Bortezomib, a therapeutic agent for multiple myeloma (MM) and mantle cell
      lymphoma, suppresses proteosomal degradation leading to substantial changes in
      cellular transcriptional programs and ultimately resulting in apoptosis.
      Transcriptional regulators required for bortezomib-induced apoptosis in MM cells
      are largely unknown. Using gene expression profiling, we identified 36
      transcription factors that displayed altered expression in MM cells treated with
      bortezomib. Analysis of a publically available database identified Kruppel-like
      family factor 9 (KLF9) as the only transcription factor with significantly higher
      basal expression in MM cells from patients who responded to bortezomib compared
      with nonresponders. We demonstrated that KLF9 in cultured MM cells was up
      regulated by bortezomib; however, it was not through the induction of endoplasmic
      reticulum stress. Instead, KLF9 levels correlated with bortezomib-dependent
      inhibition of histone deacetylases (HDAC) and were increased by the HDAC
      inhibitor LBH589 (panobinostat). Furthermore, bortezomib induced binding of
      endogenous KLF9 to the promoter of the proapoptotic gene NOXA. Importantly, KLF9
      knockdown impaired NOXA up-regulation and apoptosis caused by bortezomib, LBH589,
      or a combination of theses drugs, whereas KLF9 overexpression induced apoptosis
      that was partially NOXA-dependent. Our data identify KLF9 as a novel and
      potentially clinically relevant transcriptional regulator of drug-induced
      apoptosis in MM cells.

PMID- 22144180
TI  - FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin
      lymphoma.
AB  - Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin
      lymphoma (HL) have a highly increased risk of breast cancer. For personalized
      advice and follow-up regimens for patients, information is needed on how the
      radiotherapy-related risk is affected by other breast cancer risk factors. Genome
      wide association studies have identified 14 independently replicated common
      single nucleotide polymorphisms that influence breast cancer risk. To examine
      whether these variants contribute to risk of radiation-associated breast cancer
      in HL, we analyzed 2 independent case-control series, from the United Kingdom and
      The Netherlands, totaling 693 HL patients, 232 with breast cancer and 461
      without. rs1219648, which annotates the FGFR2 gene, was associated with risk in
      both series (combined per-allele odds ratio = 1.59, 95% confidence interval: 1.26
      2.02; P = .000111). These data provide evidence that genetic variation in FGFR2
      influences radiation-induced breast cancer risk.

PMID- 22144179
TI  - GSK-3beta regulates cell growth, migration, and angiogenesis via Fbw7 and USP28
      dependent degradation of HIF-1alpha.
AB  - The hypoxia-inducible transcription factor-1alpha (HIF-1alpha) is a major
      regulator of angiogenesis, carcinogenesis, and various processes by which cells
      adapt to hypoxic conditions. Therefore, the identification of critical players
      regulating HIF-1alpha is not only important for the understanding of angiogenesis
      and different cancer phenotypes, but also for unraveling new therapeutic options.
      We report a novel mechanism by which HIF-1alpha is degraded after glycogen
      synthase kinase-3 (GSK-3)-induced phosphorylation and recruitment of the
      ubiquitin ligase and tumor suppressor F-box and WD protein Fbw7. Further,
      experiments with GSK-3beta and Fbw7-deficient cells revealed that GSK-3beta and
      Fbw7-dependent HIF-1alpha degradation can be antagonized by ubiquitin-specific
      protease 28 (USP28). In agreement with this, Fbw7 and USP28 reciprocally
      regulated cell migration and angiogenesis in an HIF-1alpha-dependent manner.
      Therefore, we have identified a new pathway that could be targeted at the level
      of GSK-3, Fbw7, or USP28 to influence HIF-1alpha-dependent processes like
      angiogenesis and metastasis.

PMID- 22144181
TI  - Inhibiting the palmitoylation/depalmitoylation cycle selectively reduces the
      growth of hematopoietic cells expressing oncogenic Nras.
AB  - The palmitoylation/depalmitoylation cycle of posttranslational processing is a
      potential therapeutic target for selectively inhibiting the growth of hematologic
      cancers with somatic NRAS mutations. To investigate this question at the single
      cell level, we constructed murine stem cell virus vectors and assayed the growth
      of myeloid progenitors. Whereas cells expressing oncogenic N-Ras(G12D) formed
      cytokine-independent colonies and were hypersensitive to GM-CSF, mutations within
      the N-Ras hypervariable region induced N-Ras mislocalization and attenuated
      aberrant progenitor growth. Exposing transduced hematopoietic cells and bone
      marrow from Nras and Kras mutant mice to the acyl protein thioesterase inhibitor
      palmostatin B had similar effects on protein localization and colony growth.
      Importantly, palmostatin B-mediated inhibition was selective for Nras mutant
      cells, and we mapped this activity to the hypervariable region. These data
      support the clinical development of depalmitoylation inhibitors as a novel class
      of rational therapeutics in hematologic malignancies with NRAS mutations.

PMID- 22144183
TI  - Specificity and selectivity profile of EP217609: a new neutralizable dual-action
      anticoagulant that targets thrombin and factor Xa.
AB  - EP217609 is a new dual-action parenteral anticoagulant that combines an indirect
      factor Xa inhibitor (fondaparinux analog) and a direct thrombin inhibitor (alpha
      NAPAP analog) in a single molecule together with a biotin tag to allow avidin
      neutralization. EP217609 exhibits an unprecedented pharmacologic profile in
      showing high bioavailability, long plasma half-life, and potent antithrombotic
      activity in animals without the complications of thrombin rebound. Here we report
      the exceptional specificity and selectivity profile of EP217609. EP217609
      inhibited thrombin with rapid kinetics (k(on) > 10(7)M(-1)s(-1)), a high affinity
      (K(I) = 30-40pM), and more than 1000-fold selectivity over other coagulation and
      fibrinolytic protease targets, comparing favorably with the best direct thrombin
      inhibitors known. EP217609 bound antithrombin with high affinity (K(D) = 30nM)
      and activated the serpin to rapidly (k(ass) ~ 10(6)M(-1)s(-1)) and selectively (>
      20-fold) inhibit factor Xa. The dual inhibitor moieties of EP217609 acted largely
      independently with only modest linkage effects of ligand occupancy of one
      inhibitor moiety on the potency of the other (~ 5-fold). In contrast, avidin
      binding effectively neutralized the potency of both inhibitor moieties (20- to
      100-fold). These findings demonstrate the superior anticoagulant efficacy and
      rapid avidin neutralizability of EP217609 compared with anticoagulants that
      target thrombin or factor Xa alone.

PMID- 22144182
TI  - Mitochondrial dysfunction in ataxia-telangiectasia.
AB  - Ataxia-telangiectasia mutated (ATM) plays a central role in DNA damage responses,
      and its loss leads to development of T-cell malignancies. Here, we show that ATM
      loss also leads to intrinsic mitochondrial abnormalities in thymocytes, including
      elevated reactive oxygen species, increased aberrant mitochondria, high cellular
      respiratory capacity, and decreased mitophagy. A fraction of ATM protein is
      localized in mitochondria, and it is rapidly activated by mitochondrial
      dysfunction. Unexpectedly, allelic loss of the autophagy regulator Beclin-1
      significantly delayed tumor development in ATM-null mice. This effect was not
      associated with rescue of DNA damage signaling but rather with a significant
      reversal of the mitochondrial abnormalities. These data support a model in which
      ATM plays direct roles in modulating mitochondrial homeostasis and suggest that
      mitochondrial dysfunction and associated increases in mitochondrial reactive
      oxygen species contribute to the cancer-prone phenotype observed in organisms
      lacking ATM. Thus, ataxia-telangiectasia should be considered, at least in part,
      as a mitochondrial disease.

PMID- 22144184
TI  - BH3-only protein Noxa regulates apoptosis in activated B cells and controls high
      affinity antibody formation.
AB  - The efficiency of humoral immune responses depends on the selective outgrowth of
      B cells and plasma cells that produce high affinity antibodies. The factors
      responsible for affinity maturation of B cell clones in the germinal center (GC)
      have been well established but selection mechanisms that allow clones to enter
      the GC are largely unknown. Here we identify apoptosis, regulated by the
      proapoptotic BH3-only member Noxa (Pmaip1), as a critical factor for the
      selection of high-affinity clones during B cell expansion after antigen
      triggering. Noxa is induced in activated B cells, and its ablation provides a
      survival advantage both in vitro and in vivo. After immunization or influenza
      infection, Noxa(-/-) mice display enlarged GCs, in which B cells with reduced
      antigen affinity accumulate. As a consequence, Noxa(-/-) mice mount low affinity
      antibody responses compared with wild-type animals. Importantly, the low affinity
      responses correlate with increased immunoglobulin diversity, and cannot be
      corrected by booster immunization. Thus, normal elimination of low affinity cells
      favors outgrowth of the remaining high-affinity clones, and this is mandatory for
      the generation of proper antibody responses. Manipulation of this process may
      alter the breadth of antibody responses after immunization.

PMID- 22144185
TI  - Critical requirement for Stat5 in a mouse model of polycythemia vera.
AB  - The JAK2V617F mutation has been identified in most cases of Ph-negative
      myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential
      thrombocythemia (ET), and primary myelofibrosis (PMF). Expression of JAK2V617F
      results in constitutive activation of multiple signaling molecules/pathways.
      However, the key signaling downstream of JAK2V617F required for transformation
      and induction of MPNs remains elusive. Using a mouse genetic strategy, we show
      here that Stat5 is absolutely required for the pathogenesis of PV induced by
      Jak2V617F. Whereas expression of Jak2V617F in mice resulted in all the features
      of human PV, including an increase in red blood cells, hemoglobin, hematocrit,
      white blood cells, platelets, and splenomegaly, deletion of Stat5 in the
      Jak2V617F knockin mice normalized all the blood parameters and the spleen size.
      Furthermore, deletion of Stat5 completely abrogated erythropoietin (Epo)
      independent erythroid colony formation evoked by Jak2V617F, a hallmark feature of
      PV. Re-expression of Stat5 in Stat5-deficient Jak2V617F knockin mice completely
      rescued the defects in transformation of hematopoietic progenitors and the PV
      phenotype. Together, these results indicate a critical function for Stat5 in the
      pathogenesis of PV. These findings also provide strong support for the
      development of Stat5 inhibitors as targeted therapies for the treatment of PV and
      other JAK2V617F-positive MPNs.

PMID- 22144186
TI  - TFPIbeta is the GPI-anchored TFPI isoform on human endothelial cells and
      placental microsomes.
AB  - Tissue factor pathway inhibitor (TFPI) produces factor Xa-dependent feedback
      inhibition of factor VIIa/tissue factor-induced coagulation. Messages for 2
      isoforms of TFPI have been identified. TFPIalpha mRNA encodes a protein with an
      acidic N-terminus, 3 Kunitz-type protease inhibitor domains and a basic C
      terminus that has been purified from plasma and culture media. TFPIbeta mRNA
      encodes a form in which the Kunitz-3 and C-terminal domains of TFPIalpha are
      replaced with an alternative C-terminus that directs the attachment of a
      glycosylphosphatidylinositol (GPI) anchor, but whether TFPIbeta protein is
      actually expressed is not clear. Moreover, previous studies have suggested that
      the predominant form of TFPI released from cells by phosphatidylinositol-specific
      phospholipase C (PIPLC) treatment is TFPIalpha, implying it is bound at cell
      surfaces to a separate GPI-anchored coreceptor. Our studies show that the form of
      TFPI released by PIPLC treatment of cultured endothelial cells and placental
      microsomes is actually TFPIbeta based on (1) migration on SDS-PAGE before and
      after deglycosylation, (2) the lack of a Kunitz-3 domain, and (3) it contains a
      GPI anchor. Immunoassays demonstrate that, although endothelial cells secrete
      TFPIalpha, greater than 95% of the TFPI released by PIPLC treatment from the
      surface of endothelial cells and from placental microsomes is TFPIbeta.

PMID- 22144187
TI  - Pervasive exposure to violence and posttraumatic stress disorder in a
      predominantly African American Urban Community: the Detroit Neighborhood Health
      Study.
AB  - Exposure to traumatic events is common, particularly among economically
      disadvantaged, urban African Americans. There is, however, scant data on the
      psychological consequences of exposure to traumatic events in this group. We
      assessed experience with traumatic events and posttraumatic stress disorder
      (PTSD) among 1,306 randomly selected, African American residents of Detroit.
      Lifetime prevalence of exposure to at least 1 traumatic event was 87.2% (assault
      = 51.0%). African Americans from Detroit have a relatively high burden of PTSD;
      17.1% of those who experienced a traumatic event met criteria for probable
      lifetime PTSD. Assaultive violence is pervasive and is more likely to be
      associated with subsequent PTSD than other types of events. Further efforts to
      prevent violence and increase access to mental health treatment could reduce the
      mental health burden in economically disadvantaged urban areas.

PMID- 22144188
TI  - Controlling miRNA regulation in disease.
AB  - Our understanding of the importance of noncoding RNA molecules is steadily
      growing. One such important class of RNA molecules are microRNAs (miRNAs). These
      tiny RNAs fulfill important functions in cellular behavior by influencing the
      protein output levels of a high variety of genes through the regulation of target
      messenger RNAs. Moreover, miRNAs have been implicated in a wide range of
      diseases. In pathological conditions, the miRNA expression levels can be altered
      due to changes in the transcriptional or posttranscriptional regulation of miRNA
      expression. On the other side, mRNA molecules might be able to escape the
      regulation by miRNAs. In this review, we give an overview on how miRNA biogenesis
      can be altered in disease as well as how mRNAs can avoid the regulation by
      miRNAs. The interplay between these two processes defines the final protein
      output in a cell, and thus the normal or pathological cellular phenotype.

PMID- 22144189
TI  - Introduction to miRNA profiling technologies and cross-platform comparison.
AB  - MicroRNA analysis has been widely adopted for basic and applied science. The
      tools and technologies available for quantifying and analysing miRNAs are still
      maturing. Here, we give an introductory overview of the main tools and the
      challenges in their use. We also discuss the importance of basic experimental
      design, sample handling and analysis methods as the impact of these can be as
      profound as the choice of miRNA analysis platform. Whether the reader is
      interested in a gene-by-gene or genome-wide approach choosing the platform to use
      is not trivial. Careful thought given before starting an experiment will make the
      execution much easier.

PMID- 22144190
TI  - Stem-loop RT-qPCR for microRNA expression profiling.
AB  - Quantification of the microRNAs (miRNAs) in cells or tissues is a crucial step in
      understanding their biological functions. Development of the stem-loop reverse
      transcription procedure and TaqMan((r)) miRNA assays enables accurate detection
      of miRNA expression levels by quantitative PCR. Increased experimental throughput
      permits the expression screening of larger number of miRNAs with small amounts of
      sample. Here, we demonstrate the use of both TaqMan((r)) Array Card and
      OpenArray((r)) platforms to accurately determine the level of miRNA gene
      expression in biological samples.

PMID- 22144191
TI  - Poly(T) adaptor RT-PCR.
AB  - Reverse transcription PCR (RT-PCR) is one of the most important techniques for
      analyzing RNA abundance. MicroRNAs (miRNAs) are a group of 20- to 24-nucleotide
      regulatory small RNAs which play an important role in plants and animals.
      However, the small size of miRNAs makes them difficult to be detected and
      quantified by conventional RT-PCR techniques. Here, we describe a poly(T) adaptor
      RT-PCR method specifically designed for quantifying miRNAs. In this method, total
      RNAs, including miRNAs, are extended by a poly(A) tailing reaction using poly(A)
      polymerase and ATP. The miRNA with a poly(A) tail is converted into cDNA through
      reverse transcription primed by a poly(T) adaptor, and then PCR-amplified using a
      miRNA-specific forward primer and a universal poly(T) adaptor reverse primer. The
      RT-PCR amplification can be monitored by real-time detection or by end-point
      detection for quantifying the miRNA transcript level. The PCR amplicons can be
      sequenced for validating the expression of the specific miRNA gene.

PMID- 22144192
TI  - MicroRNA in situ hybridization.
AB  - In situ hybridization (ISH) is a technology that allows detection of specific
      nucleic acid sequences in tissue samples at the cellular level. For detection of
      individual microRNAs (miRNAs) and mRNAs, the ISH technology determines the
      cellular origin of expression and provides information on expression levels in
      different tissue compartments and cell populations. This histological expression
      analysis is of crucial importance for elucidating roles particularly of miRNAs in
      molecular and biological processes. mRNA expression analyses can partly be
      replaced by immunohistochemical detection of the protein encoded by the mRNA.
      Combined with the short sequences of the miRNAs (18-22 bp), this leaves miRNA ISH
      as an indispensable yet challenging technology in terms of detection and
      specificity analysis. In this chapter, a simple miRNA ISH protocol using
      chromogenic detection is presented. I touch upon critical steps in the ISH
      protocol, different applications on ISH technology platforms, advantageous use of
      locked nucleic acids (LNATM) in miRNA detection probes, qualification of clinical
      paraffin samples, and specificity analyses and quantification of the ISH signal.

PMID- 22144193
TI  - Agilent microRNA microarray profiling system.
AB  - MicroRNA (miRNA) profiling is of great interest because of the significant roles
      these short noncoding RNA molecules play in cellular regulation. Signature
      profiles, usually involving several miRNAs, have also been associated with
      dysfunctional cellular regulation such as in cancer. Profiling miRNAs can be done
      using the Agilent Technologies miRNA profiling system, which is a sensitive and
      accurate miRNA microarray assay. The assay is based on a highly efficient
      labeling method linked to a novel probe design strategy. The labeling method uses
      a simple, single-vial approach where 100 ng of nonfractionated total RNA is
      directly labeled by ligation of a Cy3 labeled pCp molecule to the 3' end of the
      RNA. The labeled cytosine interacts with the guanidine at the 5' end of the probe
      which adds stability to the hybridization complex. In addition, the probes have
      been designed to provide both sequence and size discrimination, generally
      resulting in highly specific detection of closely related mature miRNAs. The
      labeling and probe design strategies allow for a precise and accurate measurement
      that spans a linear dynamic range of greater than four orders of magnitude from
      at least 0.2 amol to 2 fmol of miRNA and a detection limit of less than 0.1 amol.
      The assay works over a wide range of sample types including FFPE samples.
      Agilent's microarray technology is a flexible design platform allowing quick
      array design iterations and incorporation of the latest miRBase content.

PMID- 22144194
TI  - miRNA expression profiling using Illumina Universal BeadChips.
AB  - We have developed a highly sensitive, specific, and reproducible method for
      microRNA (miRNA) expression profiling, using BeadArray technology. This method
      incorporates an enzyme-assisted specificity step, a solid-phase primer extension
      to distinguish between members of miRNA families. In addition, a universal PCR is
      used to amplify all targets prior to array hybridization. Using this method,
      highly reproducible miRNA expression profiles were generated with 100-200 ng
      total RNA input. The method has a 3.5-4 log (10(5)-10(9) molecules) dynamic range
      and is able to detect 1.2- to 1.3-fold differences between samples. Expression
      profiles generated by this method are highly comparable to those obtained with RT
      PCR (R (2) = 0.85-0.90) and direct sequencing (R = 0.87-0.89). This method should
      prove useful for high-throughput expression profiling of miRNAs in large numbers
      of tissue samples.

PMID- 22144196
TI  - Individualized miRNA assay panels using optically encoded beads.
AB  - This chapter describes how to create a multiplexed miRNA profiling assay using
      readily available technology and reagents for midplex miRNA profiles (midplex
      used to denote mutliplexing up to about 100 miRNAs per well). The assay described
      is a direct hybridization assay, i.e., it involves no amplification. Further, the
      reagents are simple and an assay can be assembled in a few hours with simple
      design rules and very simple execution. The assay execution takes less than 5 h
      and involves only liquid addition, which makes it possible to create a
      multiplexed assay for a large number of miRNAs and run the entire profile for
      hundreds of samples in a matter of a couple of days. In addition, the profiles
      can be created for any short RNAs, i.e., they are not tied to human or any other
      species database for miRNAs, and the described assay works for both animal and
      plant miRNAs.

PMID- 22144195
TI  - MicroRNA expression analysis using the Affymetrix Platform.
AB  - Microarrays have been used extensively for messenger RNA expression monitoring.
      Recently, microarrays have been designed to interrogate expression levels of
      noncoding RNAs. Here, we describe methods for RNA labeling and the use of a miRNA
      array to identify and measure microRNA present in RNA samples.

PMID- 22144197
TI  - Microfluidic primer extension assay.
AB  - MicroRNAs (miRNAs) are a new class of biomarkers. They represent a group of
      small, noncoding RNAs that regulate gene expression at the posttranslational
      level by degrading or blocking translation of messenger RNA (mRNA) targets.
      miRNAs are important players when it comes to regulating cellular functions and
      in several diseases, including cancer (Cancer Res 66:7390-7394, 2006; Nature
      435:834-838, 2005). So far, miRNAs have been extensively studied in tissue
      material. Only recently, it was found that miRNAs also exist in a broad range of
      body fluids (Clin Chem 56:1733-1741, 2010). A major challenge still is the
      efficient and specific detection of miRNAs. The short length of miRNAs, with only
      17-27 base pairs, comes with technical difficulties for analysis. Furthermore,
      individual miRNAs, especially members of a miRNA family (e.g., the let-7 family),
      show high sequence homology, with sequences differing by as little as a single
      base pair. Although miRNAs are abundant in higher copy numbers compared to mRNAs,
      miRNAs lack a common feature like a poly-A tail that eases detection in a complex
      background of other RNA species. Besides qPCR, in situ hybridization, and next
      generation sequencing, microarrays are versatile tools for high-throughput
      analysis of already known miRNAs (PLoS One 12:e9685, 2010; Nat Genet 38:S2-S7,
      2006; Nature Methods 50:298-301, 2010). Different assay formats have been
      proposed for expression analysis of miRNAs on microarrays, of which most employed
      prelabeled RNA molecules. As a modification, the so-called RAKE assay was
      developed that combined the use of unlabeled RNA with on-chip enzymatic labeling
      by exonuclease cleavage and polymerase primer extension (RNA 12:187-191, 2006;
      Nature Methods 1:155-161, 2004; Genome Res 16:1289-1298, 2006).Here, we describe
      a simple method for detection of miRNAs based on a combination of stringent
      hybridization and enzymatic primer extension on a microfluidic microarray
      starting from total RNA material, without the need for enrichment, amplification,
      or labeling of the native RNA samples (N Biotechnol 25:142-149, 2008). This assay
      can be used with starting material as low as 30 ng of total RNA. We have used
      this technique extensively for identifying specific sets of miRNAs (miRNA
      signatures) for diagnosis of cancer and cardiovascular or inflammatory diseases
      from blood samples of patients (Br J Cancer 103:693-700, 2010; BMC Cancer 9:353,
      2009; PLoS One 4:e7440, 2009; BMC Cancer 10:262, 2010; Basic Res Cardiol
      106(1):13-23, 2011).

PMID- 22144198
TI  - MicroRNA profiling using uParaflo microfluidic array technology.
AB  - The diverse functions of microRNA (miRNA) molecules have drawn broad and
      intensive interest in various biological fields, biomedical applications, and
      technology development. Which are endogeneous cellular short RNA molecules found
      in the cytoplasm as well as in various serum fluids. miRNAs are transcriptional
      and translational regulatory molecules active in cell division, growth, and
      apoptosis (1). Dysregulated expression of miRNAs has been implicated in various
      disease states and has been tested as biomarker candidates (2-4). miRNAs are
      endogeneous cellular short RNA molecules found in the cytoplasm as well as in
      various serum fluids. miRNAs are transcriptional and translational regulatory
      molecules active in cell division, growth, and apoptosis (Bartel, Cell 116:281
      97, 2004). Dysregulated expression of miRNAs has been implicated in various
      disease states and has been tested as biomarker candidates (He et al., Nature
      435:828-833, 2005; Lu et al., Nature 435:834-838, 2005; O'Donnell, et al., Nature
      435:839-843, 2005). In this chapter, we describe the methods using MUParaflo((r))
      microfluidic oligonucleotide microarray technology for applications in miRNA
      profiling. One unique feature of this technology is the flexibility that provides
      users with the freedom to select sequence content either for focused studies
      wherein only the most relevant sequences are included or for discovery studies
      wherein the most updated sequence content such as those newly derived from deep
      sequencing. This chapter provides detailed information from experimental design
      to sample preparation, as well as data analysis for a miRNA array experiment.

PMID- 22144199
TI  - MicroRNA expression analysis using the Illumina microRNA-Seq Platform.
AB  - Direct sequencing of RNA molecules using next-generation sequencing (NGS)
      technology has revolutionized the analysis of transcriptome with its massively
      parallel throughput and low cost. Here, we describe Illumina's microRNA-Seq, a
      method for sequencing microRNA using the Illumina Genome Analyzer system. The
      sequence data generated from this method enables direct identifying and profiling
      of microRNAs in any given organism. It also sheds light in understanding the
      biogenesis and modification of microRNA.

PMID- 22144200
TI  - Next-generation sequencing of miRNAs with Roche 454 GS-FLX technology: steps for
      a successful application.
AB  - MicroRNAs (miRNAs) are a class of small RNAs (sRNAs) of approximately 22
      nucleotides in length that control eukaryotic gene expression at the
      translational level. They regulate a wide variety of biological processes, namely
      developmental timing, cell differentiation, cell proliferation, the immune
      response, and infection. Their identification is essential to understand
      eukaryotic biology. Their small size, low abundance, and high instability
      complicated early identification, however new generation genome sequencing
      approaches, such as the Roche 454 Pyrosequencer, allow for both miRNA
      identification and for generating miRNA profiles in a given sample. This
      technique avoids cloning steps in bacteria and is a fast and bias-minimized tool
      to discover novel miRNAs and other sRNAs on a genome-wide scale. Prior to
      sequencing, cDNA libraries are built for each sample using total RNA as starter
      material. Each cDNA library can be tagged with specific identifier sequences that
      allow sequencing different samples in the same chip run. Here, we describe the
      protocols for the construction of sRNA cDNA libraries for 454 sequencing, and we
      include tips for overcoming problems often encountered during cDNA library
      preparation.

PMID- 22144201
TI  - Methods for small RNA preparation for digital gene expression profiling by next
      generation sequencing.
AB  - Digital gene expression (DGE) profiling techniques are playing an eminent role in
      the detection, localization, and differential expression quantification of many
      small RNA species, including microRNAs (1-3). Procedures in small RNA library
      preparation techniques typically include adapter ligation by RNA ligase, followed
      by reverse transcription and amplification by PCR. This chapter describes three
      protocols that were successfully applied to generate small RNA sequencing
      SOLiD(TM) libraries. The Ambion SREK(TM)-adopted protocol can be readily used for
      multiplexing samples; the modban-based protocol is cost-efficient, but biased
      toward certain microRNAs; the poly(A)-based protocol is less biased, but less
      precise because of the A-tail that is introduced. In summary, each of these
      protocols has its advantages and disadvantages with respect to the ease of
      including barcodes, costs, and outcome.

PMID- 22144202
TI  - Profiling of short RNAs using Helicos single-molecule sequencing.
AB  - The importance of short (<200 nt) RNAs in cell biogenesis has been well
      documented. These short RNAs include crucial classes of molecules such as
      transfer RNAs, small nuclear RNA, microRNAs, and many others (reviewed in Storz
      et al., Annu Rev Biochem 74:199-217, 2005; Ghildiyal and Zamore, Nat Rev Genet
      10:94-108, 2009). Furthermore, the realm of functional RNAs that fall within this
      size range is growing to include less well-characterized RNAs such as short RNAs
      found at the promoters and 3' termini of genes (Affymetrix ENCODE Transcriptome
      Project et al., Nature 457:1028-1032, 2009; Davis and Ares, Proc Natl Acad Sci
      USA 103:3262-3267, 2006; Kapranov et al., Science 316:1484-1488, 2007; Taft et
      al., Nat Genet 41:572-578, 2009; Kapranov et al., Nature 466:642-646, 2010),
      short RNAs involved in paramutation (Rassoulzadegan et al., Nature 441:469-474,
      2006), and others (reviewed in Kawaji and Hayashizaki, PLoS Genet 4:e22, 2008).
      Discovery and accurate quantification of these RNA molecules, less than 200 bases
      in size, is thus an important and also challenging aspect of understanding the
      full repertoire of cellular and extracellular RNAs. Here, we describe the
      strategies and procedures we developed to profile short RNA species using single
      molecule sequencing (SMS) and the advantages SMS offers.

PMID- 22144203
TI  - DeepBase: annotation and discovery of microRNAs and other noncoding RNAs from
      deep-sequencing data.
AB  - Recent advances in high-throughput deep-sequencing technology have produced large
      numbers of short and long RNA sequences and enabled the detection and profiling
      of known and novel microRNAs (miRNAs) and other noncoding RNAs (ncRNAs) at
      unprecedented sensitivity and depth. In this chapter, we describe the use of
      deepBase, a database that we have developed to integrate all public deep
      sequencing data and to facilitate the comprehensive annotation and discovery of
      miRNAs and other ncRNAs from these data. deepBase provides an integrative,
      interactive, and versatile web graphical interface to evaluate miRBase-annotated
      miRNA genes and other known ncRNAs, explores the expression patterns of miRNAs
      and other ncRNAs, and discovers novel miRNAs and other ncRNAs from deep
      sequencing data. deepBase also provides a deepView genome browser to
      comparatively analyze these data at multiple levels. deepBase is available at
      http://deepbase.sysu.edu.cn/.

PMID- 22144204
TI  - PhenomiR: microRNAs in human diseases and biological processes.
AB  - The association of dysregulated microRNAs (miRNAs) and diseases has been shown in
      a variety of studies. Here, we review a resource denoted as PhenomiR, providing
      systematic and comprehensive access to such studies. It allows machine-readable
      access to miRNA and target relations from these studies to study the impact of
      miRNAs on multifactorial diseases across many samples and biological replicates.
      We summarize the PhenomiR data structure and its content and show how to access
      the database and use it in everyday miRNA profile analysis using the R language.

PMID- 22144205
TI  - miRNA expression profiling: from reference genes to global mean normalization.
AB  - MicroRNAs (miRNAs) are an important class of gene regulators, acting on several
      aspects of cellular function such as differentiation, cell cycle control, and
      stemness. These master regulators constitute an invaluable source of biomarkers,
      and several miRNA signatures correlating with patient diagnosis, prognosis, and
      response to treatment have been identified. Within this exciting field of
      research, whole-genome RT-qPCR-based miRNA profiling in combination with a global
      mean normalization strategy has proven to be the most sensitive and accurate
      approach for high-throughput miRNA profiling (Mestdagh et al., Genome Biol
      10:R64, 2009). In this chapter, we summarize the power of the previously
      described global mean normalization method in comparison to the multiple
      reference gene normalization method using the most stably expressed small RNA
      controls. In addition, we compare the original global mean method to a modified
      global mean normalization strategy based on the attribution of equal weight to
      each individual miRNA during normalization. This modified algorithm is
      implemented in Biogazelle's qbasePLUS software and is presented here for the
      first time.

PMID- 22144206
TI  - miRNA data analysis: next-gen sequencing.
AB  - MicroRNAs (miRNAs) are short, noncoding RNAs that have the capacity to bind,
      capture, and silence hundreds of genes within and across diverse signaling
      pathways 1(Bartel, Cell 136:215-33, 2009) Specific sets of miRNAs characterize
      specific cell lineages of normal organisms and an increasing number of diseases
      have been shown to be associated with the dysregulation of specific miRNAs. Deep
      sequencing platforms have revealed unexpected complexity in relation to miRNAs,
      including 5' and 3'-end-length heterogeneity and RNA editing. These insights not
      uncovered by previous microarray-based studies underscore the importance of data
      analysis tools that enable users to rapidly and easily analyze the unprecedented
      amounts of small RNA sequencing data that is emerging from next-generation
      sequencing platforms, such as Illumina/Solexa, SOLiD, and 454. In this chapter,
      we summarize the increasing number of analysis platforms that are available for
      miRNA discovery and profiling and the identification of functional miRNA-mRNA
      pairs in the context of biology and disease. We also discuss in greater detail
      our contributions to this effort.

PMID- 22144207
TI  - Integrated miRNA expression analysis and target prediction.
AB  - The accurate prediction of microRNA targets is essential to understanding their
      function. Commonly used software produces a prohibitive number of predicted
      targets for each microRNA. Here, we describe procedures that refine these
      predictions by integrating available software and expression data from
      experiments available online. These procedures are tailored to experiments, where
      predicting true targets is more important than detecting all putative targets.
      Our approach is tailored to the experimental biologist who seeks to identify a
      workable set of putative microRNA target genes for further characterization.

PMID- 22144209
TI  - Blood-based miRNA preparation for noninvasive biomarker development.
AB  - This chapter describes several methods for the isolation of miRNAs from
      peripheral whole blood samples or constituent fractions thereof, such as
      peripheral blood mononuclear cells, plasma, and serum. The methods described here
      are recently introduced protocols dedicated to the isolation of total RNAs
      including small RNAs, e.g., miRNeasy Kit and PAXgene Blood miRNA Kit, or
      alternatively for the enrichment of low-molecular-weight RNA (LMW RNA) fractions
      including small RNAs, e.g., using the miRNeasy Kit. Furthermore, modifications of
      classical RNA purification protocols to facilitate the recovery of small RNAs are
      highlighted.

PMID- 22144208
TI  - miRNAs in human cancer.
AB  - MicroRNAs (miRNAs) are small (~18-25 nucleotides), endogenous, noncoding RNAs
      that regulate gene expression in a sequence-specific manner via the degradation
      of target mRNAs or the inhibition of protein translation. miRNAs are predicted to
      target up to one-third of all human mRNAs. Each miRNA can target hundreds of
      transcripts and proteins directly or indirectly, and more than one miRNA can
      converge on a single target transcript; thus, the potential regulatory circuitry
      afforded by miRNAs is enormous. Increasing evidence is revealing that the
      expression of miRNAs is deregulated in cancer. High-throughput miRNA
      quantification technologies provide powerful tools to study global miRNA
      profiles. It has become progressively more apparent that, although the number of
      miRNAs (~1,000) is much smaller than the number of protein-coding genes
      (~22,000), miRNA expression signatures more accurately reflect the developmental
      lineage and tissue origin of human cancers. Large-scale studies in human cancer
      have further demonstrated that miRNA expression signatures are associated not
      only with specific tumor subtypes but also with clinical outcomes.

PMID- 22144210
TI  - Prevalence rate and functional status of cerebellar ataxia in Korea.
AB  - Cerebellar ataxia (hereinafter referred to as CA) designate a group of
      neurodegenerative disorders. CA is distinguished into a group of hereditary and
      non-hereditary disorders. CA shows clinically progressive features and
      accompanies various neurological abnormalities. However, there are very few
      studies and case reports in Korean patients. To estimate the prevalence rate and
      current status of the CA patients in Korea, we used data from the Health
      Insurance Review and Assessment Service (HIRAS) and from the National Health
      Insurance Corporation. To evaluate the functional status of CA patient in Korea,
      we conducted a simple random sampling among the 500 members of Korea Ataxia
      Society registered on its homepage. We evaluated the functional status and degree
      of disturbance to their everyday life with modified Rankin scales and Barthel ADL
      index. Using the data from HIRAS, we could estimate the prevalence rate of CA
      patients in Korea as 8.29 patients/100,000 persons. The prevalence rate of
      hereditary and non-hereditary cerebellar ataxia was 4.99 patients/100,000 persons
      and 3.30 patients/100,000 persons, respectively. Data on rare intractable
      diseases reported by the Korean Centers for Disease Control and Prevention in
      2006 suggested that the number of CA patients who have visited medical institutes
      was almost doubled for the 2-year period. The medical expense and hospital stay
      also increased 4.5- and 3-fold, respectively. After severity evaluation with
      modified Rankin scales and Barthel ADL index, we found that most CA patients in
      Korea have ataxia-related difficulties in their everyday life.

PMID- 22144212
TI  - Prof. Anheli Syrenicz's team, in collaboration with other departments, present us
      their research achievements.

PMID- 22144213
TI  - The Department of Endocrinology of Pomeranian Medical Academy in Szczecin,
      Poland.

PMID- 22144211
TI  - The subcellular proteome of undifferentiated human embryonic stem cells.
AB  - We have characterized the subcellular proteome of human embryonic stem cells
      (hESCs) through MS analysis of the membrane, cytosolic, and nuclear fractions,
      isolated from the same sample of undifferentiated hESCs. Strikingly, 74% of all
      proteins identified were detected in a single subcellular fraction; we also
      carried out immunofluorescence studies to validate the subcellular localization
      suggested by proteomic analysis, for a subset of proteins. Our approach resulted
      in deeper proteome coverage - peptides mapping to 893, 2475, and 1185 proteins
      were identified in the nuclear, cytosolic, and membrane fractions, respectively.
      Additionally, we used spectral counting to estimate the relative abundance of all
      cytosolic proteins. A large number of proteins relevant to hESC biology,
      including growth factor receptors, cell junction proteins, transcription factors,
      chromatin remodeling proteins, and histone modifying enzymes were identified. Our
      analysis shows that components of a large number of interacting signaling
      pathways are expressed in hESCs. Finally, we show that proteomic analysis of the
      endoplasmic reticulum (ER) and Golgi compartments is a powerful alternative
      approach to identify secreted proteins since these are synthesized in the ER and
      transit through the Golgi. Taken together, our results show that systematic
      subcellular proteomic analysis is a valuable tool for studying hESC biology.

PMID- 22144214
TI  - Polymorphism of the vitamin D3 receptor gene and bone mineral density in girls
      with functional hypothalamic amenorrhea subjected to oestroprogestagen treatment.
AB  - BACKGROUND: We investigated whether the vitamin D3 receptor gene (VDR)
      polymorphism can modulate therapeutic response of functional hypothalamic
      amenorrhea (FHA) patients to the oestroprogestagen (EP) treatment. MATERIAL AND
      METHODS: The study included 84 FHA girls and 50 controls. FHA patients underwent
      a four-year sequential EP therapy with 17-beta oestradiol (2 mg from the 2(nd) to
      25(th) day of the menstrual cycle) and didrogesterone (10 mg from the 16(th) to
      the 25(th) day). Their hormonal parameters were monitored along with bone
      turnover marker levels and bone mineral density (BMD). Additionally, the VDR gene
      BsmI polymorphism was determined. RESULTS: Hormonal therapy was reflected by a
      substantial improvement of BMD. However, the values of BMD observed after four
      years of treatment in FHA patients were still significantly lower than baseline
      bone mineral density determined in the control group (1.007 +/- 0.100 vs. 1.141
      +/- 0.093 g/cm(2), respectively; p < 0.001). No significant effects of the VDR
      genotype were observed on the dynamics of BMD during consecutive years of
      hormonal treatment and mean bone mineral density determined after completing the
      therapy (1.006 +/- 0.101 vs. 1.013 +/- 0.114 vs. 1.006 +/- 0.094 g/cm(2) for BB,
      bb and Bb genotypes, respectively; p = 0.973). CONCLUSIONS: This study did not
      confirm that VDR polymorphism can modulate therapeutic outcome of FHA girls
      subjected to the hormonal treatment. Nonetheless, this study confirmed the
      effectiveness of EP therapy in the simultaneous treatment of menstrual disorders
      and the normalisation of bone mineral density in FHA patients.

PMID- 22144215
TI  - Changes in inflammatory biomarkers after successful lifestyle intervention in
      obese children.
AB  - BACKGROUND: Obesity has been associated with low-grade systemic inflammation,
      potentially leading to insulin resistance, type 2 diabetes, dyslipidemia, and
      cardiovascular diseases. Even moderate weight loss through dietary changes and
      physical exercise is effective in preventing and managing obesity-associated
      disorders. The aim of this study was to determine the effect of weight loss in
      response to a lifestyle modification on the serum levels of inflammatory markers
      in obese children and adolescents. MATERIAL AND METHODS: Fifty obese subjects
      completed a six-month programme consisting of combined hypocaloric diet and
      moderate physical activity. High-sensitive C-reactive protein (CRP), interleukin
      6 (IL-6), fibrinogen (FB), white blood count (WBC), glucose, insulin, insulin
      resistance index (HOMA IR), glycosylated haemoglobin (HbA(1c)), lipids as well as
      systolic (SBP) and diastolic blood pressure (DBP) were measured before and after
      intervention. RESULTS: Patients had a 5.3 +/- 3.4 kg average weight loss, with
      significant decreases of SDS-BMI, percentage of body fat, SDS-waist, SBP and DBP,
      HOMA-IR, HbA(1c) and reductions in serum IL-6, CRP, WBC, FB. In the multivariable
      linear models, changes in percentage of body fat and HOMA-IR were positively
      associated with favourable changes in inflammatory parameters. CONCLUSION: This
      study demonstrates that weight reduction after successful lifestyle intervention
      results in improvements of blood inflammatory markers in obese children and
      adolescents.

PMID- 22144216
TI  - Serum 25-hydroxyvitamin D (25-OH-D) in obese adolescents.
AB  - BACKGROUND: There is increasing evidence that vitamin D deficiency is common and
      has been associated with several non-bone related outcomes, including insulin
      resistance, type 2 diabetes and cardiovascular disease. The influences of gender,
      puberty, and adiposity on serum hydroxyvitamin D (25-OH-D) levels and the
      relationship between 25-OH-D and insulin resistance in obese children were
      studied. MATERIAL AND METHODS: Age, gender, pubertal stage, weight status
      (standard deviation score of body mass index: BMI-SDS, percentage body fat, waist
      circumference), 25-OH-D levels, and insulin resistance index calculated by
      homeostasis model assessment (HOMA-IR) were evaluated in 64 obese adolescents.
      Multivariable linear regression was used to determine factors associated with
      decreased serum 25-OH-D levels and to study the relationship between 25-OH-D and
      HOMA-IR. RESULTS: Median serum 25-OH-D level was 10.1 ng/mL (25.2 nmol/L). 14% of
      patients were vitamin D-sufficient (25-OH-D >= 20 ng/mL), 36% had intermediate
      values (11-19 ng/mL), and 50% were deficient (25-OH-D <= 10 ng/mL). In the
      multivariable model, older age, puberty, higher value of percentage of body fat,
      and the presence of acanthosis nigricans (AN) were all negatively associated with
      25-OH-D. Lower 25-OH-D levels were also associated with higher blood glucose,
      insulin and HOMA-IR after adjustment for puberty and SDS-BMI. Summer positively
      correlated with 25-OH-D level. CONCLUSION: Our study confirms that obesity is a
      risk factor for vitamin D deficiency. Hypovitaminosis D, common in obese
      adolescents at risk for type 2 diabetes (older age, puberty, acanthosis
      nigricans) is associated with worse insulin resistance.

PMID- 22144217
TI  - Laparoscopic adrenalectomy for functioning and non-functioning adrenal tumours.
AB  - BACKGROUND: The purpose of this study was a retrospective analysis of outcomes
      following laparoscopic adrenalectomy (LA) performed for benign adrenal tumours
      responsible for various endocrinological disorders. The patients were diagnosed
      with non-functioning (NFT) and functioning adrenal tumours (FT) including
      pheochromocytoma (PH), Conn's syndrome (CO) and Cushing's (CS) syndrome. MATERIAL
      AND METHODS: A total of 165 LAs were carried out between August 1995 and
      September 2009 via either the transperitoneal (n = 38) or retroperitoneal (n =
      127) approach. The analysed factors included demographic data of patients, the
      American Association of Anaesthesiology score (ASA), indication for surgery,
      tumour size and side, intraoperative and postoperative outcome of LA including
      duration of surgery, blood loss, time until ambulation, length of hospital stay,
      time until return to normal activity, the complication rate, as well as the
      conversion rate to open adrenalectomy. RESULTS: There were 111 patients with NFT
      and 54 with FT. Patients with NFT were significantly older than those with CO (p
      < 0.05). The mean size of the lesion differed between CO and other adrenal
      tumours (p < 0.05) as well as between NFT and PH (p < 0.05). All the lesions
      except aldosteronomas were detected predominantly in the right adrenal gland (p <
      0.05). However, despite the different characteristic and clinical disorders
      related to laparoscopically removed adrenal tumours, the intraoperative and
      postoperative outcomes did not significantly differ in most cases between the
      analysed groups of patients. CONCLUSION: This study shows that LA is a safe,
      effective, and well-tolerated procedure despite the hormonal activity of the
      removed lesions. Minimal invasive surgery may be recommended as the 'gold
      standard' in the treatment of both functioning and non-functioning benign tumours
      of the adrenal gland.

PMID- 22144218
TI  - The influence of interferon alpha on the induction of autoimmune thyroiditis in
      patients treated for chronic viral hepatitis type C.
AB  - BACKGROUND: Different forms of interferon alpha (IFN-alpha) have been used for
      several years in the treatment of chronic viral hepatitis type C (CVHC).
      Currently, pegylated forms of interferon alpha (PegIFN-alpha) in combination with
      ribavirin is the standard treatment. During therapy with IFN-alpha, side-effects
      occur, including thyroid diseases. The aim of this study was an evaluation of
      administered interferon's impact on the frequency of autoimmune thyroiditis (ATI)
      occurrence among patients with CVH type C treated with INF-alpha and an
      assessment as to whether the type of interferon used is significant in ATI
      development. MATERIAL AND METHODS: 149 patients aged 18-70 (mean 43.9 +/- 2.3
      years) with CVH type C participated in the study. The serum concentrations of
      thyrotrophin (TSH), free tyrosine (FT4), triiodothyronine (FT3), thyreoglobulin
      (Tg), antithyroid antibodies: antiperoxidase (TPOAb) and antithyreoglobulin
      (TgAb) were evaluated before, and after six and 12 months of treatment.
      Additionally, the thyroid echostructure was evaluated with ultrasonography. Sixty
      out of 149 patients received Peg-INF-alpha, and 89 patients were treated with
      recombinant IFN-alpha. RESULTS: ATI was confirmed in nine patients (6.04%) with
      CVH type C before the introduction of interferon. Seven of them underwent an
      exacerbation of hypothyroidsm during therapy with interferon. In 24 patients
      (17.14%), who did not have the signs of ATI at baseline, an elevated
      concentration of antithyroid antibodies was detected during therapy with
      interferon. The mean concentrations of TPOAb before, and after six and 12 months
      of treatment were, respectively: 12.4; 310.4 and 141.3 IU/ml, and the mean
      concentrations of TgAb were, respectively: 17.40; 108.0; and 125.6 IU/ml. After
      six months of treatment in this group of patients, 11 had hypothyroidsm and six
      had hyperthyroidsm. After 12 months of therapy, four patients had hypertthyroidsm
      and four showed signs and symptoms of hypothyroidsm; the remaining patients were
      in a euthyroid state. In ultrasound examination, reduction of echogenicity among
      patients with ATI before treatment was revealed in 75% of cases at baseline, in
      83.3% after six months and in 100% after 12 months of treatment. In the group of
      patients presenting with ATI during IFN-alpha therapy, in which no disorders were
      found in initial examination, after six months of treatment a reduction of
      echogenicity was found in 69.2%, and after 12 months in 75%, of patients.
      CONCLUSIONS: Among patients treated with interferon due to CVH type C, there is a
      risk of the development of ATI or the exacerbation of an existing one. There is
      no significant difference in ATI presentation in relation to the type of IFN
      alpha used for treatment.

PMID- 22144219
TI  - Plasma levels of NT-pro-brain natriuretic peptide in patients with overt and
      subclinical hyperthyroidism and hypothyroidism.
AB  - BACKGROUND: Several studies have assessed natriuretic peptides in patients with
      thyroid disorders, and these studies have provided contrasting results. This
      difference may be partially explained by the presence of concomitant disorders of
      the cardiovascular system in participants. MATERIAL AND METHODS: The study
      included 101 patients free of any cardiovascular disorder, who, on the basis of
      plasma levels of TSH and thyroid hormones, were divided into patients with overt
      hyperthyroidism, patients with subclinical hyperthyroidism, patients with overt
      hypothyroidism, patients with subclinical hypothyroidism, and control subjects
      with normal thyroid profile. Hyperthyroidism was induced either by nodular
      thyroid disease or by Graves' disease, while hypothyroidism was secondary to
      autoimmune thyroiditis or surgery. RESULTS: Compared to control subjects,
      hyperthyroid patients were characterised by higher plasma levels of NT-pro-BNP.
      This increase was particularly pronounced in cases of overt disease. On the other
      hand, neither clinical nor subclinical hypothyroidism was associated with any
      significant changes in this peptide. Plasma levels of NT-pro-BNP did not differ
      between patients with Graves' disease and toxic nodular goitre nor between
      patients with autoimmune hypothyroidism and hypothyroidism secondary to
      thyroidectomy. Only L-thyroxine substitutions, but not hyperthyroidism treatment,
      caused changes in plasma concentration of NT-pro-BNP. CONCLUSIONS:
      Hyperthyroidism and hypothyroidism induce changes of the plasma concentration of
      NT-pro-BNP. Although both exogenous L-thyroxine and antithyroid drugs restored
      thyroid function, only the former drug changed plasma NT-pro-BNP content. The
      thyrometabolic state of a patient should always be taken into consideration when
      NT-pro-BNP is assessed as a marker of cardiac dysfunction.

PMID- 22144220
TI  - The detection of macroprolactin by precipitation and ultrafiltration methods.
AB  - BACKGROUND: Prolactin (PRL) exists in human blood in several molecular forms.
      Macroprolactin (MaPRL), which most often consists of monomeric PRL and
      immunoglobulin G, has the highest molecular weight but no biological activity.
      Immunoassays do not distinguish MaPRL from monomeric PRL, what can lead to an
      incorrect diagnosis of hyperprolactinaemia. The most commonly used technique to
      separate the isoforms of PRL is precipitation with polyethylene glycol (PEG).
      Another technique - ultrafiltration - seems to be useful in MaPRL detection. The
      aim of this study was to evaluate the occurrence of MaPRL in hyperprolactinaemic
      patients and to compare the results obtained by precipitation and
      ultrafiltration. MATERIAL AND METHODS: The study was conducted on 120 sera
      obtained from patients hospitalised in the Department of Clinical Endocrinology,
      Medical University of Lodz, in whom PRL concentration was above 30 ng/mL Of these
      120 patients, 25 had pituitary adenoma, 52 had polycystic ovary syndrome (PCOS),
      and 43 had idiopathic hyperprolactinaemia (HPRL). Macroprolactin was detected
      using two methods: precipitation with PEG and ultrafiltration. Concentration of
      PRL was measured by Immulite 1000 immunoassay (Siemens). RESULTS: We detected a
      predominance of MaPRL in ten patients (three with macroprolactinoma, three with
      PCOS and four with HPRL) using precipitation and ultrafiltration. Positive
      correlation and diagnostic concordance between the results of precipitation and
      ultrafiltration were noted, especially in the group with functional
      hyperprolactinaemia. In half of the patients with macroprolactinaemia, and in 12
      of the 110 subjects without significant amounts of MaPRL, real PRL concentration
      was within the reference range. CONCLUSIONS: MaPRL is not a significant clinical
      problem in the studied population. However, in patients with hyperprolactinaemia,
      especially non-organic, screening for macroprolactinaemia should be performed.
      The effectiveness of the precipitation and ultrafiltration methods for detecting
      MaPRL is comparable in functional hyperprolactinaemia, but the usefulness of
      ultrafiltration in patients with pituitary adenoma requires further examination.

PMID- 22144221
TI  - Effects of oestrogen deficiency on bone mineralisation in girls during
      "adolescent crisis".
AB  - Puberty is a critical bone mineralisation period, and peak bone mass attained by
      adolescent girls is one of the most significant predictive factors for
      postmenopausal osteoporosis. Adolescent girls' peak bone mass depends on genetic
      factors as well as on general condition, nutritional status and body mass;
      lifestyle is also important, along with physical exercise and the use of
      prescription drugs. Additionally, hormones, including oestrogens, play an
      important role during pubertal accumulation of bone mass. Therefore, oestrogen
      deficiency during puberty has serious consequences for bone mineralisation.
      During puberty, particularly during the initial years after menarche,
      hypothalamic dysfunction can develop due to psycho-emotional burden, excessive
      physical exercise or increasing number of responsibilities; psychologists refer
      to this period as the "crisis of adolescence". Its symptoms include behavioural
      disorders and juvenile depression, both affecting the hypothalamic neurosecretion
      to an extent that can be reflected by secondary hypo-oestrogenism and amenorrhea.
      The administration of oestroprogestagens in the treatment of low bone mineral
      density and hypo-oestrogenism-associated menstrual disorders results in resumed
      regular menstrual bleedings and maintains, or even improves, bone mineral
      density. This observation seems to be important not only in terms of short term
      clinical applications, but also in the context of the long term prevention of
      osteoporosis. Consequently, hormonal therapy has to be accompanied by a thorough
      education of patients and their parents, particularly in terms of proper
      nutrition and modification of levels of physical activity. Puberty is the optimal
      time period for modifying environmental factors that are associated with bone
      mass gain.

PMID- 22144222
TI  - Late diagnosis of type 2B multiple endocrine neoplasia (MEN 2B) in a 23 year-old
      patient.
AB  - We present a case of MEN 2B diagnosed in a 23 year-old patient on the basis of
      bilateral pheochromocytoma and medullary thyroid carcinoma. This young male
      patient also had multiple paragangliomas located along the spine, marfanoid
      features of body habitus and numerous mucosal neuromas of the oral cavity and
      intestinal ganglioneuromatosis. The patient was hospitalised several times
      between the ages of 11 and 14 due to heart rhythm disorders (tachycardia,
      multiple supraventricular beats) and pain in the precardiac area. Elevated blood
      pressure was not observed at that time. In 2010, the patient was admitted to
      hospital due to abdominal pain, nausea, vomiting and hypertension; bilateral
      adrenal tumours were then detected. The patient was referred to the Department of
      Endocrinology in Szczecin, with suspected pheochromocytoma in order to continue
      the diagnostic process. This resulted in the diagnosis of bilateral
      pheochromocytoma and medullary thyroid carcinoma. On the basis of the whole
      clinical picture, the diagnosis of MEN 2B was established and subsequently
      confirmed with genetic test results. Following the removal of adrenal tumours and
      thyroidectomy, the patient was referred to the Cancer Centre and Institute of
      Oncology in Gliwice for further treatment (X-ray therapy and further surgery due
      to recurrence of medullary carcinoma). This article presents a case of late MEN
      2B diagnosis despite the presence of clinical symptoms suggestive of Multiple
      Endocrine Neoplasia observed from early childhood.

PMID- 22144223
TI  - Familial acromegaly - case study of two sisters with acromegaly.
AB  - In the majority of cases, acromegaly is sporadic. However, it can also occur in a
      familial setting as a component of MEN-1, MEN-4, Carney complex (CNC) or as the
      extremely rare syndrome of isolated familial somatotropinoma (IFS), the latter
      belonging to familial isolated pituitary adenomas (FIPA). The diagnosis of IFS is
      based on the recognition of acromegaly/gigantism in at least two family members,
      given that the family is not affected by MEN-1, MEN-4 or CNC. The authors present
      a case study of two sisters: a 56 year-old patient (case no. 1) and a 61 year-old
      patient (case no. 2). In both sisters, acromegaly was recognised in the course of
      pituitary macroadenoma. Neither of the sisters showed features of MEN-1, MEN-4 or
      Carney complex. The authors suppose that the presented cases are manifestations
      of IFS. However, this diagnosis has not been confirmed yet because of the poor
      availability of genetic tests.

PMID- 22144224
TI  - Hypogonadotropic hypogonadism in women.
AB  - This article presents the role of the hypothalamus in reproduction, the
      definition of hypogonadotropic hypogonadism (HH), and the causes of acquired and
      syndromic HH and idiopathic HH (IHH). The authors present a short review of major
      causes of acquired HH, but most of the causes of IHH will not be discussed
      because they do not fall within the scope of the article. More attention is
      devoted to idiopathic HH, especially the genetic basis of IHH. Also presented in
      the article are clinical criteria of CHARGE syndrome. Later, the article
      discusses the clinical presentation, establishing the diagnosis, and management
      of IHH. The article ends with a brief overview of nutritional hypothalamic
      dysfunction and athletic amenorrhea.

PMID- 22144225
TI  - Optimization of environmental factors for improved production of rhamnolipid
      biosurfactant by Pseudomonas aeruginosa RS29 on glycerol.
AB  - A biosurfactant producing Pseudomonas aeruginosa RS29 (identified on the basis of
      16S rDNA analysis) with good foaming and emulsification properties has been
      isolated from crude oil contaminated sites. Optimization of different
      environmental factors was carried out with an objective to achieve maximum
      production of biosurfactant. Production of biosurfactant was estimated in terms
      of surface tension reduction and emulsification (E24) index. It was recorded that
      the isolated strain produced highest biosurfactant after 48 h of incubation at
      37.5  degrees C, with a pH range of 7-8 and at salinity <0.8% (w/v). Ammonium
      nitrate used in the experiment was the best nitrogen source for the growth of
      biomass of P. aeruginosa RS29. On the other hand sodium and potassium nitrate
      enhanced the production of biosurfactant (Surface tension, 26.3 and 26.4 mN/m and
      E24 index, 80 and 79% respectively). The CMC of the biosurfactant was 90 mg/l.
      Maximum biomass (6.30 g/l) and biosurfactant production (0.80 g/l) were recorded
      at an optimal C/N ratio of 12.5. Biochemical analysis and FTIR spectra confirmed
      that the biosurfactant was rhamnolipid in nature. GC-MS analysis revealed the
      presence of C(8) and C(10) fatty acid components in the purified biosurfactant.

PMID- 22144226
TI  - Psammoma bodies in fine needle aspiration cytology of the breast: a
      clinicopathological study of 30 cases.
AB  - Psammoma bodies (PBs) in breast lesions are rare and little is known about the
      role of these structures in breast pathology. This study has looked in to the
      diagnostic significance of PBs in fine needle aspiration (FNAC) of breast
      lesions. Over a 5-year period, FNACs of the breast were done in 4,563 subjects,
      of which 1,678 were diagnosed to be malignant. On review of all breast aspirates
      including non-neoplastic lesions, 30 cases showed PBs to be associated with
      breast carcinoma (BC). Cytological features were correlated with clinical,
      radiological, histological, and immunohistochemical findings. All 30 aspirates
      and their corresponding histological sections showed varying number of PBs and
      nonpsammomatous bodies (NPBs). For comparison, 31 cases of age-matched BC without
      PBs and NPBs in both aspirates and sections were studied. Statistical analysis
      using Chi-square test was done to compare BC with and without PBs. BC with PBs
      was characterized by papillary pattern of malignant cells, mucin in the
      background, infiltration by macrophages, cellular degeneration, overexpression of
      estrogen receptor (ER), and progesterone receptor (PR) and moderate positivity
      (2+) for Her2/neu. Calcium deposition has long been implicated in the
      pathogenesis of many degenerative diseases; hence the formation of PBs may be
      relevant in breast oncology. The presence of PBs in FNAC of clinically suspected
      breast lesions which are cytologically negative for malignancy warrants further
      histological confirmation.

PMID- 22144227
TI  - Functional magnetic resonance imaging using PROPELLER-EPI.
AB  - Periodically rotated overlapping parallel lines with enhanced reconstruction-echo
      planar imaging (PROPELLER-EPI) is a multishot technique that samples k-space by
      acquisition of narrow blades, which are subsequently rotated until the entire k
      space is filled. It has the unique advantage that the center of k-space, and thus
      the area containing the majority of functional MRI signal changes, is sampled
      with each shot. This continuous refreshing of the k-space center by each acquired
      blade enables not only sliding-window but also keyhole reconstruction. Combining
      PROPELLER-EPI with a fast gradient-echo readout scheme allows for high spatial
      resolutions to be achieved while maintaining a temporal resolution, which is
      suitable for functional MRI experiments. Functional data acquired with a novel
      interlaced sequence that samples both single-shot EPI and blades in an
      alternating fashion suggest that PROPELLER-EPI can achieve comparable functional
      MRI results. PROPELLER-EPI, however, features different spatiotemporal
      characteristics than single-shot EPI, which not only enables keyhole
      reconstruction but also makes it an interesting alternative for many functional
      MRI applications.

PMID- 22144228
TI  - Enhanced structural stability of Concholepas hemocyanin increases its
      immunogenicity and maintains its non-specific immunostimulatory effects.
AB  - Hemocyanins, which boost the immune system of mammals, have been used as carrier
      adjuvants to promote Ab production against haptens and peptides, as
      immunostimulants during therapy for bladder carcinoma and as a component in
      therapeutic vaccines for cancer. These biomedical applications have led to
      growing interest in obtaining hemocyanins with high immunogenicity. Here, we
      study the immunological properties of a modified oxidized Concholepas concholepas
      hemocyanin (Ox-CCH) obtained by the oxidation of its carbohydrates using sodium
      periodate. We assessed the internalization of Ox-CCH into DCs and its
      immunogenicity and antitumor effects. Transmission electron microscopy showed no
      changes in Ox-CCH quaternary structure with respect to native CCH, although
      proteolytic treatment followed by SDS-PAGE analysis demonstrated that Schiff
      bases were formed. Interestingly, DCs internalized Ox-CCH faster than CCH, mainly
      through macropinocytosis. During this process, Ox-CCH remained inside endosome
      like structures for a longer period. Mouse immunization experiments demonstrated
      that Ox-CCH is more immunogenic and a better carrier than CCH. Moreover, Ox-CCH
      showed a significant antitumor effect in the B16F10 melanoma model similar to
      that produced by CCH, inducing IFN-gamma secretion. Together, these data
      demonstrate that the aldehydes formed by the periodate oxidation of sugar
      moieties stabilizes the CCH structure, increasing its adjuvant/immunostimulatory
      carrier effects.

PMID- 22144229
TI  - Electrochemical oxidation of benzene to phenol.
AB  - Gas-phase electrochemistry: The direct hydroxylation of benzene to phenol was
      investigated using an electrochemical cell. The production of phenol over a VO(x)
      anode was found to be significant at 50  degrees C. The resultant current
      efficiency for phenol production and selectivity toward phenol reached 76.5 and
      94.7 %, respectively.

PMID- 22144230
TI  - Narrative quality and disturbance pre- and post-emotion-focused therapy for child
      abuse trauma.
AB  - This study predicted that the quality of trauma narratives written before and
      following emotion-focused therapy for child abuse trauma would be positively
      associated with psychological disturbance before and following therapy.
      Narratives for 37 clients were coded for emotion words, temporal orientation,
      incoherence, and depth of experiencing. At pretreatment, negative emotion words
      and experiencing were correlated with abuse resolution, r(35) = -.36, and r(35) =
      -.34, respectively. At posttreatment, narrative incoherence was correlated with
      trauma symptoms, r(35) = .33, whereas present-future orientation and experiencing
      were correlated with abuse resolution, r(35) = -.37, and r(35) = -.31,
      respectively. Pretreatment incoherence was associated with posttreatment trauma
      symptoms, r(35) = .42, and pretreatment depth of experiencing was associated with
      posttreatment abuse resolution, r(35) = -.37. Results support narrative quality
      as an index of trauma disturbance.

PMID- 22144231
TI  - First experience with the wearable cardioverter defibrillator in the Netherlands.
AB  - The implantable cardioverter defibrillator (ICD) has significantly improved
      survival in patients with an increased risk of sudden cardiac death (SCD). The
      wearable cardioverter defibrillator (WCD) is an alternative to the ICD in
      patients with a transient ICD indication or those in whom an ICD temporarily
      cannot be implanted. We describe here the technical details of the WCD and report
      three patients who were treated with a WCD in an outpatient setting. The WCD
      allowed the cardiac condition of two patients to improve to such an extent that
      permanent ICD implantation was deemed unnecessary. This new form of therapy may
      result in significant cost reduction, avoidance of unnecessary ICD implantation,
      and increased patient satisfaction.

PMID- 22144232
TI  - Isolation of fetal gonads from embryos of timed-pregnant mice for morphological
      and molecular studies.
AB  - Gonadal sex differentiation is an important developmental process, in which a
      bipotential primordial gonad undergoes two distinct pathways, i.e., testicular
      and ovarian differentiation, dependent on its genetic sex. Techniques of
      isolating fetal gonads at various developmental stages are valuable for studies
      on the molecular events involved in cell-fate determination, sex-specific somatic
      and germ-cell differentiation and structural organization. Here we describe
      various procedures for isolation of embryonic gonads at different developmental
      stages from embryos of timed-pregnant mice. The isolated fetal gonads can be used
      for a variety of studies, such as organ culture, gene and protein expression. As
      examples of applications, we describe the immunofluorescence detection of SOX9
      expression in gonadal tissue sections and microRNAs profiling/expression in fetal
      gonads at a critical stage for sex determination.

PMID- 22144233
TI  - Neonatal testicular gonocytes isolation and processing for immunocytochemical
      analysis.
AB  - In recent years, an increasing interest has emerged at understanding how
      spermatogonial stem cells (SSCs) arise from their precursor cells, the gonocytes.
      The identification of factors acting directly on gonocytes rather than on the
      surrounding somatic cells and the study of genes and signaling pathways intrinsic
      to gonocytes require their isolation from Sertoli and peritubular cells. The
      present article describes a simple method developed to isolate rat neonatal
      gonocytes, allowing for the study of their proliferation and differentiation to
      SSCs. We also present immunocytochemical methods that can be used to study
      protein expression changes and proliferation in gonocytes.

PMID- 22144234
TI  - Isolation of undifferentiated and early differentiating type A spermatogonia from
      Pou5f1-GFP reporter mice.
AB  - Limited understanding of the mechanisms underlying self-renewal and
      differentiation of spermatogonial stem cells hampers our ability to develop new
      therapeutic and contraceptive approaches. Mouse models of spermatogonial stem
      cell development are key to developing new insights into the biology of both the
      normal and diseased testis. Advances in transgenic reporter mice have enabled the
      isolation, molecular characterization, and functional analysis of mouse Type A
      spermatogonia subpopulations from the normal testis, including populations
      enriched for spermatogonial stem cells. Application of these reporters both to
      the normal testis and to gene-deficient and over-expression models will promote a
      better understanding of the earliest steps of spermatogenesis, and the role of
      spermatogonial stem cells in germ cell tumor.

PMID- 22144235
TI  - Isolation of human male germ-line stem cells using enzymatic digestion and
      magnetic-activated cell sorting.
AB  - Mammalian spermatogenesis is a process whereby male germ-line stem cells
      (spermatogonial stem cells) divide and differentiate into sperm. Although a great
      deal of progress has been made in the isolation and characterization of
      spermatogonial stem cells (SSCs) in rodents, little is known about human SSCs. We
      have recently isolated human G protein-coupled receptor 125 (GPR125)-positive
      spermatogonia and GDNF family receptor alpha 1 (GFRA1)-positive spermatogonia
      using a 2-step enzymatic digestion and magnetic-activated cell sorting (MACS)
      from adult human testes. Cell purities of isolated human GPR125- and GFRA1
      positive spermatogonia after MACS are greater than 95%, and cell viability is
      over 96%. The isolated GPR125- and GFRA1-positive spermatogonia coexpress GPR125,
      integrin, alpha 6 (ITGA6), THY1 (also known as CD90), GFRA1, and ubiquitin
      carboxyl-terminal esterase L1 (UCHL1), markers for rodent or pig
      SSCs/progenitors, suggesting that GPR125- and GFRA1-positive spermatogonia are
      phenotypically the SSCs in human testis. Human GPR125-positive spermatogonia can
      be cultured for 2 weeks with a remarkable increase in cell number.
      Immunocytochemistry further reveals that GPR125-positive spermatogonia can be
      maintained in an undifferentiated state in vitro. Collectively, the methods using
      enzymatic digestion and MACS can efficiently isolate and purify SSCs from adult
      human testis with consistent and high quality. The ability of isolating and
      characterizing human SSCs could provide a population of stem cells with high
      purity for mechanistic studies on human SSC self-renewal and differentiation as
      well as potential applications of human SSCs in regenerative medicine.

PMID- 22144236
TI  - Isolation and purification of murine male germ cells.
AB  - Seminiferous tubules of the male testis contain somatic cells (Sertoli and Leydig
      cells) and germ cells at different stages of spermatogenesis (spermatogonia,
      spermatocytes and spermatids). Germ cells at different stages of differentiation
      migrate toward the central lumen via cell junctions formed by Sertoli cells. The
      protocol described herein consists of the dissection and decapsulation of the
      testes, disruption of the structure of the seminiferous tubules, and the breaking
      of cell junctions to release all the cells in suspension. Germ cells are then
      separated from Sertoli cells by overnight plating of the suspension on plastic to
      which the germ cells preferentially adhere. And finally, a BSA gradient allows a
      high-purity separation of the various types of germ cells according to size.

PMID- 22144237
TI  - Preparation of enriched mouse syncitia-free pachytene spermatocyte cell
      suspensions.
AB  - Spermatogenesis comprises a complex succession of steps of mitosis, meiosis, and
      differentiation, starting with the commitment of diploid spermatogonial stem
      cells to differentiate and ending with the formation of haploid spermatozoa.
      Rodent models have been routinely used to study germ cell development and
      reproductive toxicology, since they present many similarities with their human
      counterpart while offering the advantage of recapitulating within a few weeks a
      process that normally takes years to occur. This article describes a method to
      isolate subpopulations of adult germ cells, more specifically pachytene
      spermatocytes, using two successive gradients, without using an elutriation
      centrifuge, a specialized device not available in many laboratories. Moreover,
      the method was designed to isolate enriched pachytene spermatocytes preparations
      devoid of contaminating syncitia, often formed in response to toxicants or
      environmental insults.

PMID- 22144238
TI  - Revealing the transcriptome landscape of mouse spermatogonial cells by tiling
      microarray.
AB  - In the past decade, the advent of microarray technologies has allowed functional
      genomic studies of male germ cell development, resulting in the identification of
      genes governing various processes. A major limitation with conventional gene
      expression microarray is that results obtained are biased due to gene probe
      design. The gene probes for expression microarrays are usually represented by a
      small number of probes located at the 3' end of a transcript. Tiling microarrays
      eliminate such issue by interrogating the genome in an unbiased fashion through
      probes tiled across the entire genome. These arrays provide higher genomic
      resolution and allow the identification of novel transcripts. To reveal the
      complexity of the genomic landscape of developing male germ cells, we applied
      tiling microarray to evaluate the transcriptome in spermatogonial cells. Over 50%
      of all known mouse genes are expressed during testicular development. More than
      47% of the transcripts are uncharacterized. The results suggested that the
      transcription machinery in spermaotogonial cells is more complex than previously
      envisioned.

PMID- 22144239
TI  - Biochemical characterization of a testis-predominant isoform of N-alpha
      acetyltransferase.
AB  - N-alpha protein acetylation, catalyzed by N-alpha acetyltransferase complex, is a
      common protein -modification process in eukaryotic cells. Despite its widespread
      occurrence, the biological significance of this modification process is still
      unclear. We recently discovered a novel testis-predominant isoform of the
      catalytic subunit of the enzyme complex. Here, we describe the biochemical
      characterization of this testis-predominant N-alpha acetyltransferase complex,
      which includes protein-protein interaction study by co-immunoprecipitation
      experiment and functional study by N-alpha acetyltransferase assay.

PMID- 22144240
TI  - Identification of novel long noncoding RNA transcripts in male germ cells.
AB  - Emerging evidence from these studies suggested that the male germ cell
      transcriptome is more complex than previously envisioned. In addition to protein
      coding genes, the transcriptome also encodes a significant number of nonprotein
      coding transcripts. These noncoding (nc) RNAs appear to be involved in a variety
      of cellular activities, ranging from simple housekeeping to complex regulatory
      functions. A class of ncRNAs known as long ncRNAs (lncRNAs) were recently shown
      to be expressed in a developmentally regulated manner during brain and embryonic
      stem cell development. This protocol aims to predict and identify potential
      lncRNA candidates using Serial Analysis of Gene Expression (SAGE) data. We also
      illustrate how to validate the potential lncRNAs by expression analyses using
      real-time PCR and Northern Blot. Potential lncRNA candidates in male germ cells
      are identified using our previously established male germ cell SAGE database
      (GermSAGE).

PMID- 22144241
TI  - Methylation profiling using methylated DNA immunoprecipitation and tiling array
      hybridization.
AB  - DNA methylation is an important epigenetic modification that regulates
      development and plays a role in the pathophysiology of many diseases. It is
      dynamically changed during germline development. Methylated DNA
      immunoprecipitation (MeDIP) is an efficient, cost-effective method for locus
      specific and genome-wide analysis. Methylated DNA fragments are enriched by a 5
      methylcytidine-recognizing antibody, therefore allowing the analysis of both CpG
      and non-CpG methylation. The enriched DNA fragments can be amplified and
      hybridized to tiling arrays covering CpG islands, promoters, or the entire
      genome. Comparison of different methylomes permits the discovery of
      differentially methylated regions that might be important in disease- or tissue
      specific expression. Here, we describe an established MeDIP protocol and tiling
      array hybridization method for profiling methylation of testicular germ cells.

PMID- 22144242
TI  - Spermatogenesis in cryptorchidism.
AB  - Cryptorchidism or undescended testis is the most frequent congenital abnormality
      in newborn boys. The process of testicular descent to the scrotum is controlled
      by hormones produced in Leydig cells, insulin-like3, and androgens. Variation in
      genetic and environmental factors might affect testicular descent. A failure of
      spermatogenesis and germ cell apoptosis resulting in infertility as well as an
      increased risk of neoplastic transformation of germ cell are the direct
      consequences of cryptorchidism in adulthood.

PMID- 22144243
TI  - In vitro culture of fetal ovaries: a model to study factors regulating early
      follicular development.
AB  - Follicular development commences with the formation of primordial follicles,
      which begins with the differentiation of pluripotent ovarian somatic cells into
      early granulosa cells and their apposition to the oocytes in the egg nest. The
      process of primordial follicle morphogenesis and factors affecting the formation
      and development of primordial follicles can be examined in vitro using fetal
      ovaries in organ culture. The functions of candidate genes involved in primordial
      folliculogenesis can be examined using siRNA or shRNA, which can knockdown
      specific mRNA targets at specific time points. Here, we describe the organ
      culture protocol for fetal hamster ovary with GPR30 siRNA as an example. The
      method to morphologically analyze follicular development is also discussed.

PMID- 22144244
TI  - Microspread ovarian cell preparations for the analysis of meiotic prophase
      progression in oocytes with improved recovery by cytospin centrifugation.
AB  - Female fertility is critically influenced by two events affecting oocytes during
      meiotic prophase progression: meiotic recombination between homologous
      chromosomes; and a major oocyte loss. It is technically challenging to examine
      these events, which take place in fetal and neonatal ovaries in mammals. Here, we
      describe a protocol for the preparation of dissociated ovarian cells and their
      spread onto histology slides. These preparations are suitable for cytogenetic,
      quantitative, and FISH analyses.

PMID- 22144245
TI  - In vitro maturation (IVM) of porcine oocytes.
AB  - Oocyte maturation is a critical component of in vitro embryo production. If not
      carried out in a precise manner under optimal conditions, subsequent
      fertilization and embryo development will be compromised. Here, we describe
      collection and in vitro maturation procedures in swine that maintain oocyte
      competence, resulting in successful embryo development following fertilization.
      These procedures can be used both for basic research purposes and large-scale
      production of mature oocytes for use in subsequent assisted reproductive
      technologies.

PMID- 22144246
TI  - Experimental approaches to the study of human primordial germ cells.
AB  - The survival, proliferation, and differentiation of primordial germ cells in the
      mammalian embryo is regulated by a complex cocktail of growth factors and
      interactions with surrounding somatic cells, which together form a
      microenvironment known as the germ cell niche. Extensive insight into the
      signalling pathways that regulate PGC behaviour has been provided by the study of
      these cells in rodent models, however little is known about the factors that
      regulate these processes in human PGCs. In this review, we outline experimental
      approaches to the culture and manipulation of the first trimester human fetal
      ovary, and discuss immunohistochemical and stereological approaches to detect
      changes in human PGC numbers and proliferation in response to treatment with
      exogenous growth factors.

PMID- 22144248
TI  - DNA methylation analysis of germ cells by using bisulfite-based sequencing
      methods.
AB  - Dynamic changes in DNA methylation at the gene-specific and genome-wide level
      occur during mammalian germ-cell development. However, the details of how the
      methylation profiles change remain largely unknown. Bisulfite sequencing analysis
      is a powerful technique to determine the methylation status of DNA at individual
      cytosine-guanine dinucleotide (CpG) sites and requires only a small amount of DNA
      for analysis. Here, we introduce two methods for bisulfite-based DNA methylation
      analyses using small samples such as germ cells: bisulfite Sanger sequencing at a
      specific locus and high-throughput bisulfite sequencing at the whole genome
      level.

PMID- 22144247
TI  - Investigating the origins of somatic cell populations in the perinatal mouse
      ovaries using genetic lineage tracing and immunohistochemistry.
AB  - Genetic lineage tracing (or fate mapping) techniques are designed to permanently
      label progenitor cells of target tissues, thereby allowing delineation of the
      progenies of labeled cells during organogenesis. This technology has been widely
      used in the study of cell migration and lineage specification in various organs
      and organisms. Here, we describe how to apply the genetic lineage tracing model
      in combination with immunohistochemistry to identify the potential origins of
      somatic cell precursors in perinatal mouse ovaries.

PMID- 22144249
TI  - Gene expression in mouse oocytes by RNA-Seq.
AB  - Second-generation sequencers such as the Illumina GAIIx make possible the study
      of all transcribed loci in a genome across an almost endless dynamic range.
      Although typical protocols call for starting from at least 1 MUg of total RNA,
      this is not possible when studying small tissues or rare cell types. This chapter
      explains how to prepare Illumina sequencing libraries from mouse oocytes. The
      protocol is also suitable for mural and cumulus cells, flow sorted or laser
      captured cells.

PMID- 22144250
TI  - CScore: a simple yet effective scoring function for protein-ligand binding
      affinity prediction using modified CMAC learning architecture.
AB  - Protein-ligand docking is a computational method to identify the binding mode of
      a ligand and a target protein, and predict the corresponding binding affinity
      using a scoring function. This method has great value in drug design. After
      decades of development, scoring functions nowadays typically can identify the
      true binding mode, but the prediction of binding affinity still remains a major
      problem. Here we present CScore, a data-driven scoring function using a modified
      Cerebellar Model Articulation Controller (CMAC) learning architecture, for
      accurate binding affinity prediction. The performance of CScore in terms of
      correlation between predicted and experimental binding affinities is benchmarked
      under different validation approaches. CScore achieves a prediction with R =
      0.7668 and RMSE = 1.4540 when tested on an independent dataset. To the best of
      our knowledge, this result outperforms other scoring functions tested on the same
      dataset. The performance of CScore varies on different clusters under the leave
      cluster-out validation approach, but still achieves competitive result. Lastly,
      the target-specified CScore achieves an even better result with R = 0.8237 and
      RMSE = 1.0872, trained on a much smaller but more relevant dataset for each
      target. The large dataset of protein-ligand complexes structural information and
      advances of machine learning techniques enable the data-driven approach in
      binding affinity prediction. CScore is capable of accurate binding affinity
      prediction. It is also shown that CScore will perform better if sufficient and
      relevant data is presented. As there is growth of publicly available structural
      data, further improvement of this scoring scheme can be expected.

PMID- 22144251
TI  - Discovery and evaluation of potential sonic hedgehog signaling pathway inhibitors
      using pharmacophore modeling and molecular dynamics simulations.
AB  - Sonic hedgehog (Shh) plays an important role in the activation of Shh signaling
      pathway that regulates preservation and rebirth of adult tissues. An abnormal
      activation of this pathway has been identified in hyperplasia and various
      tumorigenesis. Hence the inhibition of this pathway using a Shh inhibitor might
      be an efficient way to treat a wide range of malignancies. This study was done in
      order to develop a lead chemical candidate that has an inhibitory function in the
      Shh signaling pathway. We have generated common feature pharmacophore models
      using three-dimensional (3D) structural information of robotnikinin, an inhibitor
      of the Shh signaling pathway, and its analogs. These models have been validated
      with fit values of robotnikinin and its analogs, and the best model was used as a
      3D structural query to screen chemical databases. The hit compounds resulted from
      the screening docked into a proposed binding site of the Shh named pseudo-active
      site. Molecular dynamics (MD) simulations were performed to investigate detailed
      binding modes and molecular interactions between the hit compounds and functional
      residues of the pseudo-active site. The results of the MD simulation analyses
      revealed that the hit compounds can bind the pseudo-active site with high
      affinity than robotnikinin. As a result of this study, a candidate inhibitor (GK
      03795) was selected as a potential lead to be employed in future Shh inhibitor
      design.

PMID- 22144252
TI  - Folding elastic transmembrane helices to fit in a low-resolution image by
      electron microscopy.
AB  - Structure prediction of membrane proteins could be constrained and thereby
      improved by introducing data of the observed molecular shape. We studied a coarse
      grained molecular model that relied on residue-based dummy atoms to fold the
      transmembrane helices of a protein in the observed molecular shape. Based on the
      inter-residue potential, the alpha-helices were folded to contact each other in a
      simulated annealing protocol to search optimized conformation. Fitting the model
      into a three-dimensional volume was tested for proteins with known structures and
      resulted in a fairly reasonable arrangement of helices. In addition, the
      constraint to the packing transmembrane helix with the two-dimensional region was
      tested and found to work as a very similar folding guide. The obtained models
      nicely represented alpha-helices with the desired slight bend. Our structure
      prediction method for membrane proteins well demonstrated reasonable folding
      results using a low-resolution structural constraint introduced from recent cell
      surface imaging techniques.

PMID- 22144253
TI  - SRMBuilder: a user-friendly tool for selected reaction monitoring data analysis.
AB  - With high sensitivity and reproducibility, selected reaction monitoring (SRM) has
      become increasingly popular in proteome research for targeted quantification of
      low abundance proteins and post translational modification. SRM is also well
      accepted in other mass-spectrometry based research areas such as lipidomics and
      metabolomics, which necessitates the development of easy-to-use software for both
      post-acquisition SRM data analysis and quantification result validation. Here, we
      introduce a software tool SRMBuilder, which can automatically parse SRM data in
      multiple file formats, assign transitions to compounds, match light/heavy
      transition/compound pairs and provide a user-friendly graphic interface to
      manually validate the quantification result at transition/compound/sample level.
      SRMBuilder will greatly facilitate processing of the post-acquisition data files
      and validation of quantification result for SRM. The software can be downloaded
      for free from http://www.proteomics.ac.cn/software/proteomicstools/index.htm as
      part of the software suite ProteomicsTools.

PMID- 22144254
TI  - A transcriptome analysis by lasso penalized Cox regression for pancreatic cancer
      survival.
AB  - Pancreatic cancer is the fourth leading cause of cancer deaths in the United
      States with five-year survival rates less than 5% due to rare detection in early
      stages. Identification of genes that are directly correlated to pancreatic cancer
      survival is crucial for pancreatic cancer diagnostics and treatment. However, no
      existing GWAS or transcriptome studies are available for addressing this problem.
      We apply lasso penalized Cox regression to a transcriptome study to identify
      genes that are directly related to pancreatic cancer survival. This method is
      capable of handling the right censoring effect of survival times and the
      ultrahigh dimensionality of genetic data. A cyclic coordinate descent algorithm
      is employed to rapidly select the most relevant genes and eliminate the
      irrelevant ones. Twelve genes have been identified and verified to be directly
      correlated to pancreatic cancer survival time and can be used for the prediction
      of future patient's survival.

PMID- 22144255
TI  - Inference of S-system models of gene regulatory networks using immune algorithm.
AB  - The S-system model is one of the nonlinear differential equation models of gene
      regulatory networks, and it can describe various dynamics of the relationships
      among genes. If we successfully infer rigorous S-system model parameters that
      describe a target gene regulatory network, we can simulate gene expressions
      mathematically. However, the problem of finding an optimal S-system model
      parameter is too complex to be solved analytically. Thus, some heuristic search
      methods that offer approximate solutions are needed for reducing the
      computational time. In previous studies, several heuristic search methods such as
      Genetic Algorithms (GAs) have been applied to the parameter search of the S
      system model. However, they have not achieved enough estimation accuracy. One of
      the conceivable reasons is that the mechanisms to escape local optima. We applied
      an Immune Algorithm (IA) to search for the S-system parameters. IA is also a
      heuristic search method, which is inspired by the biological mechanism of
      acquired immunity. Compared to GA, IA is able to search large solution space,
      thereby avoiding local optima, and have multiple candidates of the solutions.
      These features work well for searching the S-system model. Actually, our
      algorithm showed higher performance than GA for both simulation and real data
      analyses.

PMID- 22144256
TI  - Introduction. Progresses in genome informatics.

PMID- 22144257
TI  - Characterization of an anti-listerial enterocin from wheat silage based
      Enterococcus faecium.
AB  - Two Enterococcus faecium and one E. faecalis strains isolated and identified from
      wheat silage were characterized based on plasmid content, hemolytic activity,
      antibiotic resistance patterns, bacteriocin production potential, and presence of
      enterocin structural genes (entA, entB, entP, entL50B). Among the isolates, only
      the E. faecium U7 strain exhibited bacteriocin activity against Listeria
      monocytogenes ATCC 7644, and vancomycin resistant Enterococcus spp. (VRE). A
      combination of three structural genes (entA, entB, and entP) was detected in E.
      faecium U7. A relationship between the presence of enterocin structural genes,
      and bacteriocin activity was detected in E. faecium U7; therefore partially
      purified enterocin (PPE) was further investigated from the isolate. Several bands
      of different molecular weights were expressed from PPE extracts following tricine
      SDS-PAGE analysis. However, the only band showing bacteriocin activity was in an
      approximate 4-kDa region. PPE treatment with proteinase K, lysozyme, and alpha 
      amylase caused complete loss of bacteriocin activity. PPE heat treatment at
      various temperatures resulted in a notable reduction in bacteriocin expression.
      Enterocin U7 was relatively heat stable, and presumably exhibits a glucoprotein
      nature with distinct inhibitory properties. Specific bacterial inhibitory
      activity of enterocin U7, and the producer strain absence of beta -hemolysis and
      vancomycin susceptibility features deserves further investigation to evaluate its
      potential application in silage inoculation and food preservation.

PMID- 22144258
TI  - High-resolution sodium imaging of human brain at 7 T.
AB  - The feasibility of high-resolution sodium magnetic resonance imaging on human
      brain at 7 T was demonstrated in this study. A three-dimensional anisotropic
      resolution data acquisition was used to address the challenge of low signal-to
      noise ratio associated with high resolution. Ultrashort echo-time sequence was
      used for the anisotropic data acquisition. Phantoms and healthy human brains were
      studied on a whole-body 7-T magnetic resonance imaging scanner. Sodium images
      were obtained at two high nominal in-plane resolutions (1.72 and 0.86 mm) at a
      slice thickness of 4 mm. Signal-to-noise ratio in the brain image (cerebrospinal
      fluid) was measured as 14.4 and 6.8 at the two high resolutions, respectively.
      The actual in-plane resolution was measured as 2.9 and 1.6 mm, 69-86% larger than
      their nominal values. The quantification of sodium concentration on the phantom
      and brain images enabled better accuracy at the high nominal resolutions than at
      the low nominal resolution of 3.44 mm (measured resolution 5.5 mm) due to the
      improvement of in-plane resolution.

PMID- 22144259
TI  - Expression of IL-1Rrp2 by human myelomonocytic cells is unique to DCs and
      facilitates DC maturation by IL-1F8 and IL-1F9.
AB  - We report for the first time that expression of the novel IL-1 cytokine receptor
      IL-1Rrp2 (IL-1R6) is unique to DCs within the human myelomonocytic lineage. IL
      1Rrp2 was expressed by monocyte-derived dendritic cells (MDDCs) which was dose
      dependently increased by IL-4 and correlated with increased numbers of
      differentiated MDDCs. Human plasmacytoid DCs also express IL-1Rrp2 but the
      receptor is not expressed by either myeloid DC type 1 (mDC1) or mDC2 cells. We
      also show that IL-1F8 or IL-1F9 cytokines, which signal through IL-1Rrp2, induce
      maturation of MDDCs, as measured by increased expression of HLA-DR and CD83 and
      decreased expression of CD1a. Furthermore, IL-1F8 stimulated increased CD40 and
      CD80 expression and IL-18 and IL-12 p70 production by MDDCs, which induced
      proliferation of IFN-gamma-producing CD3(+)  lymphocytes (indicative of
      inflammatory Th1 subsets). IL-1F8 and IL-1F2 were equipotent in their ability to
      stimulate IL-18 secretion from MDDCs but IL-1F8 was not as potent as IL-1F2 in
      stimulating secretion of IL-12p70 from MDDCs or inducing lymphocyte proliferation
      Therefore, IL-1Rrp2 expression by some DC subsets may have an important function
      in the human immune response in vivo via its role in differentiation of
      inflammatory Th1 lymphocytes.

PMID- 22144260
TI  - Lateral pterygoid muscle: a three-dimensional analysis of neuromuscular
      partitioning.
AB  - The lateral pterygoid (LP) has been implicated in temporomandibular joint (TMJ)
      pathology. Few studies have examined muscle architecture of the superior (SLP)
      and inferior (ILP) heads of LP; moreover, the pattern of intramuscular
      innervation is poorly defined. The purpose of this study was to determine
      patterns of intramuscular innervation of LP using 3D modeling. The superior and
      lateral aspects of LP were exposed in 10 embalmed cadaveric specimens. Nerves
      entering the muscle, all branches of the mandibular nerve (V(3) ), were followed
      intramuscularly in short segments and sequentially digitized. Muscle volume,
      surrounding bone, and the TMJ disc were also digitized. The data were
      reconstructed into 3D models (Maya(r)) that were used to determine patterns of
      intramuscular innervation. It was found that the SLP had independent sources of
      innervation to each of the quadrants in its superior part (masseteric/posterior
      deep temporal/middle deep temporal/buccal) and one primary source of innervation
      (buccal) to the quadrants of the inferior part. This difference in innervation is
      significant as the superior part attaches to the TMJ disc-capsule complex,
      whereas the inferior part attaches to the mandibular condylar neck. Differing
      sites of attachment and sources of innervation for each part suggests that
      movement of the TMJ disc-capsule complex, independent of the condyle, may be
      possible. The buccal nerve supplied both the medial and lateral quadrants of the
      ILP, with the medial quadrants receiving additional innervation from V(3)
      muscular branches. Results of this study could be used to direct EMG/ultrasound
      studies of LP function as related to TMJ disorders.

PMID- 22144262
TI  - Synthesis and methane-binding properties of disulfide-linked cryptophane-0.0.0.

PMID- 22144261
TI  - RAFT-derived polymer-drug conjugates: poly(hydroxypropyl methacrylamide) (HPMA)-7
      ethyl-10-hydroxycamptothecin (SN-38) conjugates.
AB  - A series of well-defined polymer-drug conjugates were prepared in order to modify
      the physical properties of a known cytotoxic drug, 7-ethyl-10-hydroxycamptothecin
      (SN-38), the active metabolite of irinotecan (CPT-11). Reversible addition
      fragmentation chain transfer (RAFT) polymerisation was used to covalently and
      site-specifically append a defined N-(2-hydroxypropyl)methacrylamide (HPMA)
      polymer to SN-38 using a graft-from process. These poly-HPMA-SN-38 conjugates
      displayed excellent aqueous solubility and stability, whilst retaining the
      cytotoxic activity of the parent SN-38. In vitro co-culture assays containing
      both cancer and noncancer cell lines demonstrated the specificity of RAFT-derived
      poly-HPMA-SN-38 conjugates for cancerous cells. The concept of post-optimisation
      modification of small-molecule drugs through a graft-from polymer conjugation
      method is introduced.

PMID- 22144263
TI  - Cardiovascular risk: gender differences in lifestyle behaviors and coping
      strategies.
AB  - BACKGROUND: Although cardiovascular disease (CVD) does not occur until mid to
      late life for most adults, the presence of risk factors, such as high blood
      pressure (BP) and cholesterol, has increased dramatically in young adults.
      PURPOSE: The present study examined the relationships between gender and coping
      strategies, lifestyle behaviors, and cardiovascular risks. METHOD: The sample
      consisted of 297 (71% female) university students. Participants completed a
      survey to assess demographics, lifestyle behaviors, and coping strategies, and a
      physiological assessment including lipid and blood pressure (BP) measurements.
      Data collection occurred from January 2007 to May 2008. RESULTS: Analyses
      revealed that age, ethnicity, greater body mass index (BMI), greater use of
      social support, and less frequent exercise were associated with higher
      cholesterol, while gender, age, greater BMI, and less frequent exercise were
      associated with higher systolic BP. There were two significant interactions: one
      between gender and avoidant coping and the other between gender and exercise on
      systolic BP, such that for men greater use of avoidant coping or exercise was
      associated with lower systolic BP. CONCLUSION: Understanding how young adults
      manage their demands and cope with stress sets the stage for understanding the
      developmental process of CVD. Both coping strategies and lifestyle behaviors must
      be considered in appraising gender-related cardiovascular risk at an early age
      before the disease process has begun.

PMID- 22144264
TI  - Historical overview of Rho GTPases.
AB  - In 1985, the first members of the Rho GTPase family were identified. Over the
      next 10 years, rapid progress was made in understanding Rho GTPase signalling.
      Multiple Rho GTPases were discovered in a wide range of eukaryotes, and shown to
      regulate a diverse range of cellular processes, including cytoskeletal dynamics,
      NADPH oxidase activation, cell migration, cell polarity, membrane trafficking,
      and transcription. The Rho regulators, guanine nucleotide exchange factors
      (GEFs), GTPase-activating proteins (GAPs), and guanine nucleotide dissociation
      inhibitors (GDIs), were found through a combination of biochemistry, genetics,
      and detective work. Downstream targets for Rho GTPases were also rapidly
      identified, and linked to Rho-regulated cellular responses. In parallel, a wide
      range of bacterial proteins were found to modify Rho proteins or alter their
      activity in cells, many of which turned out to be useful tools to study Rho
      functions. More recent work has delineated where Rho GTPases act in cells, the
      molecular pathways linking some of them to specific cellular responses, and their
      functions in the development of multicellular organisms.

PMID- 22144265
TI  - Rho GTPases: deciphering the evolutionary history of a complex protein family.
AB  - Rho GTPases constitute a significant subgroup of the eukaryotic Ras superfamily
      of small GTPases implicated in the regulation of diverse cellular processes, such
      as the dynamics of the actin cytoskeleton, establishment, and maintenance of cell
      polarity and membrane trafficking. Whereas a few eukaryotes lack Rho genes, a
      majority of species typically bear multiple Rho paralogs, raising a question
      about the origin of the family and the paths of its diversification in individual
      eukaryotic lineages. In this chapter, we ruminate on several aspects of the
      evolutionary history of the Rho family and methodological challenges of its
      reconstruction. First, we provide an updated survey of Rho GTPases in diverse
      eukaryotic branches, demonstrating almost ubiquitous occurrence of Rho genes
      across the eukaryotic phylogeny most consistent with the presence of at least one
      Rho gene already in the last eukaryotic common ancestor. Second, we discuss the
      obstacles in reconstructing the history of gene duplications giving rise to the
      extant diversity of Rho paralogs in different species, and point to numerous
      limitations posed by the current phylogenetic methodology. Third, as a case study
      demonstrating various issues of data collection, phylogenetic analyses and
      interpretations of trees, we present an analysis of the Rho family in the fungal
      kingdom, revealing the existence of at least four separate paralogs (Cdc42, Rac,
      Rho1, and Rho4) in early fungi and subsequent potentially independent expansions
      of the family in different fungal subgroups. We conclude with the warning that
      the currently dominating perception of the Rho phylogeny is biased by the
      metazoan (and especially vertebrate) perspective, and a new, more global view is
      to be worked out when a better genome sampling and more adequate methods of
      phylogenetic inference are employed.

PMID- 22144266
TI  - Biochemical assays to characterize Rho GTPases.
AB  - Rho GTPases act as tightly regulated molecular switches governing a large variety
      of critical cellular functions. Their activity is controlled by two different
      biochemical reactions, the GDP/GTP exchange and the GTP hydrolysis. These very
      slow reactions require catalysis in cells by two kinds of regulatory proteins.
      While the guanine nucleotide exchange factors (GEFs) activate small GTPases by
      stimulating the exchange of bound GDP for the cellular abundant GTP, GTPase
      activating proteins (GAPs) accelerate the intrinsic rate of GTP hydrolysis by
      several orders of magnitude, leading to their inactivation. There are a number of
      methods that can be used to characterize the specificity and activity of such
      regulators to understand the effect of binding on the protein structure and,
      ultimately, to gain insights into their biological functions. This chapter
      describes (1) detailed protocols for the expression and purification of Rho
      GTPases, of -effector-binding domains, and catalytic domains of GEFs and GAPs;
      (2) the preparation of nucleotide-free and fluorescent nucleotide-bound Rho
      GTPases; and (3) methods for monitoring the intrinsic and GEF-catalyzed
      nucleotide exchange, the intrinsic and GAP-stimulated GTP hydrolysis, and the
      effector interaction with active GTPase (three alternative approaches).

PMID- 22144267
TI  - How to analyze bacterial toxins targeting Rho GTPases.
AB  - Bacterial pathogens developed several strategies to overcome defense systems of
      eukaryotic hosts. Within the infection process, they need to attach to and cross
      through epithelial layers, escape from the innate and adaptive immune response,
      and find a physiological niche to survive. One target to modulate the host
      pathogen interaction in order to deceit pathogen resistance is the actin
      cytoskeleton and its regulators: the family of Rho GTPases. Some bacterial toxins
      catalyze a covalent modification of Rho GTPases to keep these molecular switches
      in a constitutive active or inactive state. This leads to rearrangement of the
      actin cytoskeleton. Toxin-treated cells show typical morphological changes
      depending on substrate specificity and action of the toxins. In this chapter, we
      discuss the classes of bacterial toxins based on their mode of action, their
      recombinant expression (specifically CNF1), intoxication and subsequent
      morphological changes of the actin cytoskeleton, and cell shape.

PMID- 22144268
TI  - Assessing ubiquitylation of Rho GTPases in mammalian cells.
AB  - Rho GTPases including RhoA, Cdc42, and Rac1 are master regulators of cell
      cytoskeleton dynamic, thus controlling essential cellular processes notably cell
      polarity, migration and cytokinesis. These GTPases undergo a spatiotemporal
      regulation primarily controlled by cellular factors inducing both the exchange of
      GDP for GTP and the hydrolysis of GTP into GDP. Recent findings have unveiled
      another layer of complexity in the regulation of Rho proteins consisting in their
      ubiquitylation followed by their proteasomal degradation. Here, we describe how
      to assess the level of ubiquitylation of Rho proteins in cells, taking Rac1 as an
      example.

PMID- 22144269
TI  - Posttranslational lipid modification of Rho family small GTPases.
AB  - The Rho family comprises a major branch of the Ras superfamily of small GTPases.
      A majority of Rho GTPases are synthesized as inactive, cytosolic proteins. They
      then undergo posttranslational modification by isoprenoid or fatty acid lipids,
      and together with additional carboxyl-terminal sequences target Rho GTPases to
      specific membrane and subcellular compartments essential for function. We
      summarize the use of biochemical and cellular assays and pharmacologic inhibitors
      instrumental for the study of the role of posttranslational lipid modifications
      and processing in Rho GTPase biology.

PMID- 22144270
TI  - Analysis of the role of RhoGDI1 and isoprenylation in the degradation of
      RhoGTPases.
AB  - RhoGDI1 is one of the three major regulators of the Rho switch along with RhoGEFs
      and RhoGAPs. RhoGDI1 extracts prenylated Rho proteins from lipid membranes,
      sequesters them in the cytosol, and prevents nucleotide exchange or hydrolysis.
      In addition, RhoGDI1 protects prenylated Rho proteins from degradation. Here, we
      describe techniques to monitor Rho proteins degradation upon depletion of RhoGDI1
      and their dependence upon prenylation for degradation.

PMID- 22144271
TI  - A quantitative fluorometric approach for measuring the interaction of RhoGDI with
      membranes and Rho GTPases.
AB  - Tight regulation of Rho GTPase-signaling functions requires the proper
      localization of proteins to the membrane and cytosolic compartments, which can
      themselves undergo reconfiguration in response to signaling events. The
      importance of lipid-mediated membrane signal transduction continues to emerge as
      a critical event in many Rho GTPase-signaling pathways. Here we describe methods
      for the reconstitution of lipid-modified Rho GTPases with defined lipid vesicles
      and how this system can be used as a real-time assay for monitoring protein
      membrane interactions.

PMID- 22144272
TI  - Rho GTPases and cancer cell transendothelial migration.
AB  - Small Rho GTPases are major regulators of actin cytoskeleton dynamics and
      influence cell shape and migration. The expression of several Rho GTPases is
      often up-regulated in tumors and this frequently correlates with a poor prognosis
      for patients. Migration of cancer cells through endothelial cells that line the
      blood vessels, called transendothelial migration or extravasation, is a critical
      step during the metastasis process. The use of siRNA technology to target
      specifically each Rho family member coupled with imaging techniques allows the
      roles of individual Rho GTPases to be investigated. In this chapter we describe
      methods to assess how Rho GTPases affect the different steps of cancer cell
      transendothelial cell migration in vitro.

PMID- 22144273
TI  - Quantitative and robust assay to measure cell-cell contact assembly and
      maintenance.
AB  - Epithelial junction formation and maintenance are multistep processes that rely
      on the clustering of macromolecular complexes. These events are highly regulated
      by signalling pathways that involve Rho small GTPases. Usually, when analysing
      the contribution of different components of Rho-dependent pathways to cell-cell
      adhesion, the localisation of adhesion receptors at junctions is evaluated by
      immunofluorescence. However, we find that this method has limitations on the
      quantification (dynamic range), ability to detect partial phenotypes and to
      differentiate between the participation of a given regulatory protein in assembly
      and/or maintenance of cell-cell contacts.In this chapter, we describe a suitable
      method, the aggregation assay, in which we adapted a quantitative strategy to
      allow objective and reproducible detection of partial phenotypes. Importantly,
      this methodology estimates the ability of cells to form junctions and their
      resistance to mechanical shearing forces (stabilisation).

PMID- 22144274
TI  - Rho GTPase knockout induction in primary keratinocytes from adult mice.
AB  - Primary keratinocytes are an important tool to investigate the molecular
      mechanism underlying the skin phenotype of mice with null mutations in Rho GTPase
      genes. If the RhoA gene deletion is conditional, the knockout can be induced in
      vitro by transfection with cre-IRES-GFP and sorting for GFP positive cells by
      flow cytometry. Such in vitro knockout will allow determining the cell autonomous
      functions of the Rho GTPase, independent of any in vivo interactions. Using the
      same method, also other expression vectors or knockdown constructs can be
      introduced into primary mouse keratinocytes.

PMID- 22144275
TI  - Rho GTPase techniques in osteoclastogenesis.
AB  - Historically, in vitro culturing of primary osteoclasts involved co-culturing of
      mononuclear monocytes with bone marrow stromal cells, thereby providing the
      cytokines required for osteoclast formation and multinucleation. Since the
      identification and cloning of receptor activator of nuclear factor kappa B ligand
      (RANKL), culturing primary osteoclasts in vitro has become much simplified. It
      has become apparent that the actin cytoskeleton is extremely important for the
      osteoclast, not only in terms of structural support, but also for adhesion,
      polarization, and migration. Rho family GTPases are key regulators of the actin
      cytoskeleton. In this chapter, we describe simple techniques in culturing primary
      osteoclasts from murine bone marrow cells, evaluating the activation states of
      Rho GTPases in osteoclasts, measuring the migratory abilities of monocytes, and
      introducing proteins of interest into osteoclasts using the TAT construct.

PMID- 22144276
TI  - Assessment of Rho GTPase signaling during neurite outgrowth.
AB  - Rho GTPases are key regulators of the cytoskeleton during the process of neurite
      outgrowth. Based on overexpression of dominant-positive and negative Rho GTPase
      constructs, the classic view is that Rac1 and Cdc42 are important for neurite
      elongation whereas RhoA regulates neurite retraction in response to collapsing
      agents. However, recent work has suggested a much finer control of spatiotemporal
      Rho GTPase signaling in this process. Understanding this complexity level
      necessitates a panel of more sensitive tools than previously used. Here, we
      discuss a novel assay that enables the biochemical fractionation of the neurite
      from the soma of differentiating N1E-115 neuronal-like cells. This allows for
      spatiotemporal characterization of a large number of protein components,
      interactions, and post-translational modifications using classic biochemical and
      also proteomics approaches. We also provide protocols for siRNA-mediated
      knockdown of genes and sensitive assays that allow quantitative analysis of the
      neurite outgrowth process.

PMID- 22144277
TI  - Assessment of the role for Rho family GTPases in NADPH oxidase activation.
AB  - Rac, a member of the Rho family small GTPases, plays a crucial role in activation
      of Nox family NADPH oxidases in animals, enzymes dedicated to production of
      reactive oxygen species such as superoxide. The phagocyte oxidase Nox2, crucial
      for microbicidal activity during phagocytosis, is activated in a manner
      completely dependent on Rac. Rac in the GTP-bound form directly binds to the
      oxidase activator p67( phox ), which in turn interacts with Nox2, leading to
      superoxide production. Rac also participates in activation of the nonphagocytic
      oxidase Nox1; in this case, GTP-bound Rac functions by interacting with Noxa1, a
      p67( phox )-related protein that is required for Nox1 activation. On the other
      hand, in the presence of either p67( phox ) or Noxa1, Rac facilitates superoxide
      production by Nox3, which is responsible in the inner ear for formation of
      otoconia, tiny mineralized structures that are required for sensing balance and
      gravity. All the three mammalian homologs of Rac (Rac1, Rac2, and Rac3), but not
      Cdc42 or RhoA, are capable of serving as an activator of Nox1-3. Here, we
      describe methods for the assay of Rac binding to p67( phox ) and Noxa1 and for
      the reconstitution of Rac-dependent Nox activity in cell-free and whole-cell
      systems.

PMID- 22144278
TI  - Multiplex imaging of Rho family GTPase activities in living cells.
AB  - Here, we provide procedures for imaging the Rho GTPase biosensors in both single
      and multiplex acquisition modes. The multiplex approach enables the direct
      visualization of two biosensor readouts from a single living cell. Here, we take
      as an example a combination of the RhoA biosensor based on a CFP/YFP FRET
      modality and the Cdc42 biosensor based on organic dyes that change fluorescence
      as a function of the local solvent polarity. We list the required optical
      components as well as cellular manipulation techniques necessary to successfully
      image these two ratiometric biosensors in a single living cell.

PMID- 22144279
TI  - FRET-based imaging of Rac and Cdc42 activation during Fc-receptor-mediated
      phagocytosis in macrophages.
AB  - Fluorescence resonance energy transfer (FRET) imaging can measure the spatial and
      temporal distributions of activated Rho GTPases within living cells. This
      information is essential for understanding how signaling networks influence Rho
      GTPase switching and for elucidating the mechanisms of Rho GTPase control of the
      cytoskeleton. This chapter describes FRET microscopy methods to image the
      distribution of GTP-bound Rac and Cdc42 during the well-defined morphological
      transitions of phagocytosis by macrophages. Specifically, we describe the use of
      FRET microscopy to detect the binding of genetically encoded fluorescent protein
      fusions to Rac1 or Cdc42 with a fluorescent protein fusion to a p21-binding
      domain (PBD) that recognizes their GTP-bound states. We focus on quantifying the
      kinetics and activation levels of Rac and Cdc42 during Fc receptor-mediated
      phagocytosis by macrophages. This process is a Rac1, Cdc42, and actin-dependent
      process, by which macrophages engulf particles ranging in size from 0.5 to 20 MUm
      and is an ideal model system for studying the spatial and temporal control of
      these GTPases. Quantitative FRET analysis for measuring the fractions of
      activated GTPase to allow comparison between cells, independent of the relative
      expression levels of the fluorescent fusions is also discussed.

PMID- 22144280
TI  - High-throughput flow cytometry bead-based multiplex assay for identification of
      Rho GTPase inhibitors.
AB  - Rho family GTPases and their effector proteins regulate a wide range of cell
      signaling pathways. In normal physiological conditions, their activity is tightly
      controlled and it is not surprising that their aberrant activation contributes to
      tumorigenesis or other diseases. For this reason, the identification of small,
      cell permeable molecules capable of inhibition of Rho GTPases can be
      extraordinarily useful, particularly if they are specific and act
      reversibly.Herein, we describe a flow cytometric assay, which allows us to
      measure the activity of six small GTPases simultaneously. GST-tagged small
      GTPases are bound to six glutathione bead sets each set having a different
      intensity of red fluorescence at a fixed wavelength. The coated bead sets were
      washed, combined, and dispensed into 384-well plates with test compounds, and
      fluorescent-GTP binding was used as the read-out.This multiplex bead-based assay
      was successfully used for to identify both general and selective inhibitors of
      Rho family GTPases.

PMID- 22144281
TI  - Functional analysis of Rho GTPase activation and inhibition in a bead-based
      miniaturized format.
AB  - Extensive knowledge about protein-protein interactions is fundamental to fully
      understand signaling pathways and for the development of new drugs. Rho GTPases
      are key molecules in cellular signaling processes and their deregulation is
      implicated in the development of a variety of diseases such as neurofibromatosis
      type 2 and cancer. Here, we describe a bead-based protein-protein interaction
      assay for overexpressed HA-tagged Rho GTPases to study the GTPgammaS-dependent
      interaction with the regulatory protein RhoGDIalpha. This assay provides a useful
      tool for the analysis of both macromolecular and small molecule activators and
      inhibitors of the protein-protein interactions of Rho GTPases with their
      regulatory proteins in a multiplexed miniaturized format.

PMID- 22144282
TI  - Use of phage display for the identification of molecular sensors specific for
      activated Rho.
AB  - We describe a phage display approach to select active Rho-specific scFv sensors.
      This in vitro technique allows preserving the antigen conformation stability all
      along the selection process. We used the GTP locked RhoBQ63L mutant as antigen
      against the Griffin.1 library composed of a human synthetic V(H) + V(L) scFv
      cloned in the pHEN2 phagemid vector. The method described here has permitted to
      identify an scFv that discriminates between the activated and the inactivated
      form of the Rho subfamily.

PMID- 22144283
TI  - Identification of new interacting partners for atypical Rho GTPases: a SILAC
      based approach.
AB  - In contrast to typical Rho GTPases the regulation of atypical Rho GTPases, such
      as the members of the RhoBTB subfamily, rarely depends on GEFs and/or GAPs.
      Instead, they are regulated at the level of their expression, by post
      translational modifications, by their rate of degradation as well as through
      binding of diverse cell-specific interactors. Stable Isotope Labeling by Amino
      acids in Cell culture (SILAC) is a powerful cutting-edge mass-spectrometry-based
      technology allowing for protein-interaction studies in vitro with removal of
      false-positive identifications. In this chapter, we describe how the SILAC
      technology can be applied to the identification of new interacting partners for
      atypical - constitutively active - Rho GTPases, i.e. RhoBTB3.

PMID- 22144284
TI  - Using zebrafish for studying Rho GTPases signaling in vivo.
AB  - Rho small GTPases play pivotal roles in a variety of dynamic cellular processes
      including cytoskeleton rearrangement, cell migration, cell proliferation, cell
      survival, and gene regulation. However, their functions in vivo are much less
      understood. Recently, the zebrafish, Danio rerio has emerged as a powerful model
      organism for developmental and genetic studies. Zebrafish embryos have many
      unique characteristics, such as optical transparency, external fertilization and
      development, and amenability for various molecular manipulations including
      morpholino oligo-mediated gene knockdown, mRNA or DNA overexpression-induced gain
      of function or rescue, in situ hybridization (ISH) with riboprobes for gene
      expression, western blot for protein analysis, small-molecule inhibition on
      signaling pathways, and bioimaging for tracking of molecular events. Taking many
      of such advantages, we have demonstrated the role of rhoA small GTPase in the
      control of gastrulation cell movements and cell survival during early zebrafish
      embryogenesis, linking RhoA functions to at least the noncanonical Wnt, Mek/Erk,
      and Bcl2 signaling nodes in vivo. Here, we describe the use of such techniques,
      including gene knockdown by morpholino oligo, functional rescue by mRNA
      overexpression, microinjection, ISH, western blot analysis and pharmacological
      inhibition of signaling pathways by small molecule inhibitors, with special
      considerations on their merits, potential drawbacks, and adaptation which could
      pave the way to our better understanding of the roles of various classes of small
      GTPases in regulating cell dynamics and development in vivo.

PMID- 22144285
TI  - Analysis of Rho GTPase function in axon pathfinding using Caenorhabditis elegans.
AB  - We provide information and protocols for the analysis of Rho GTPase function in
      axon pathfinding in Caenorhabditis elegans. The powerful molecular, genetic,
      imaging, and transgenic tools available in C. elegans make it an excellent system
      in which to study the in vivo roles of Rho GTPases. Methods for imaging of axon
      morphology in Rho GTPase single and double mutants are provided, as well as
      methods for the construction of transgenic C. elegans strains carrying
      exogenously introduced transgenes that drive the expression of constitutively
      active and dominant negative mutants.

PMID- 22144286
TI  - Protocol for ex vivo incubation of Drosophila primary post-embryonic haemocytes
      for real-time analyses.
AB  - The cellular branch of the Drosophila larval innate immune system consists of
      three immunosurveillance (haemocyte) cell types: plasmatocytes, crystal cells,
      and lamellocytes. In order to examine haemocyte cytoskeletal dynamics or
      migration, most researchers use embryos or in vitro cell culture systems, but
      very little is known about the behaviour of post-embryonic haemocytes. The
      current method employs an ex vivo system, in which post-embryonic haemocytes are
      isolated for short-term analysis, in order to investigate various aspects of
      their behaviour during events requiring cytoskeleton dynamics and Rho GTPase
      signalling.

PMID- 22144287
TI  - Analysis of Rho GTPase activation in Saccharomyces cerevisiae.
AB  - Rho proteins act as molecular switches to control multiple cellular processes.
      The switch mechanism involves cycling between active and inactive states based on
      GTP loading and hydrolysis. Assays that quantitatively analyze the GTP loading of
      Rho proteins have become important molecular tools to decipher upstream signals
      and mechanisms that regulate activation and de-activation. These assays make use
      of Rho activation probes constructed from Rho-binding domains of downstream
      effectors. The utility of these assays comes from effector domains that show
      selective high affinity interactions with specific subsets of GTP-bound activated
      GTPases. Here, we describe assays used to analyze yeast Rho GTPase activation.

PMID- 22144288
TI  - Assaying Rho GTPase-dependent processes in Dictyostelium discoideum.
AB  - The model organism D. discoideum is well suited to investigate basic questions of
      molecular and cell biology, particularly those related to the structure,
      regulation, and dynamics of the cytoskeleton, signal transduction, cell-cell
      adhesion, and development. D. discoideum makes use of Rho-regulated signaling
      pathways to reorganize its cytoskeleton during chemotaxis, endocytosis, and
      cytokinesis. In this organism the Rho family encompasses 20 members, several
      belonging to the Rac subfamily, but there are no representatives of the Cdc42 and
      Rho subfamilies. Here we present protocols suitable for monitoring the actin
      polymerization response and the activation of Rac upon stimulation of aggregation
      competent cells with the chemoattractant cAMP.

PMID- 22144289
TI  - FRAP-based analysis of Rho GTPase-dependent polar exocytosis in pollen tubes.
AB  - The regulation of exocytosis by Rho GTPases is conserved in eukaryotic kingdoms.
      Given the spatiotemporal dynamics of Rho GTPase activity, a method for
      visualizing exocytosis with high space and time resolution will be an important
      tool for the functional analysis of Rho GTPases. During tip growth of pollen
      tubes, both cell wall material and plasma membrane are renewed via rapid
      exocytosis. ROP1 GTPase, a plant Rho GTPase, is localized to the apical plasma
      membrane of pollen tubes and controls polar exocytosis via regulation of F-actin
      dynamics. Here, we describe a fluorescence recovery after photobleaching (FRAP)
      method for the analysis of exocytosis dynamics in living pollen tubes. This
      method has been shown to be a valuable tool for studying the effect of ROP1
      dependent F-actin dynamics on polar exocytosis in pollen tubes and may also be
      applicable to other systems.

PMID- 22144290
TI  - Active N(2)O emission from bacterial microbiota of Andisol farmland and
      characterization of some N(2)O emitters.
AB  - Andisol in farmland located in Hokkaido, Japan, is known to actively flux nitrous
      oxide (N(2)O) during the spring to summer seasons. Using a culturing system which
      mimics farm soils, nitrous oxide (N(2)O) emission potentials of the soils or soil
      microorganisms were investigated. A total of thirty-three soil samples from the
      farmland showed high N(2)O production potential, of which the maximum level of
      N(2)O emission was 3.69 MUg per ml of the cultured medium per day (ml(-1) d(-1))
      in the assay system. However, only three eubacteria (Leptothrix sp.,
      Paenibacillus sp., and Streptomyces sp.) were isolated as culturable N(2)O
      emitters among a total of 92 bacterial isolates and 2 fungi obtained from the
      assayed soil suspensions. N(2)O production from all the isolated N(2)O emitters
      was more active within a weakly acidic region (pH 4.5-5.0) than neutral regions.
      However, unlike N(2)O emitters isolated from tropical peat soils, they did not
      respond to supplemental 0.5% sucrose. In the acetylene inhibition assay for the
      evaluation of complete denitrification, Leptothrix sp. P3-15D and Streptomyces
      sp. M2-0C indicated that these culturable N(2)O emitters are not effective
      denitrifiers but weak N(2)O emitters in the Andisol. Conversely, Rhodococcus sp.
      that was isolated from the Andisol collected in another season using a KNO(3)
      enriched plate, showed 3.2-fold higher N(2)O emission with 10% C(2) H(2). Instead
      of the culturable bacteria, it is probable that the N(2)O emitters in viable but
      non-culturable (VBNC) state or obligately anaerobic denitrifiers are the major
      contributors to N(2)O emission from the vitric Andisol.

PMID- 22144291
TI  - Correlation between single-trial visual evoked potentials and the blood
      oxygenation level dependent response in simultaneously recorded
      electroencephalography-functional magnetic resonance imaging.
AB  - To compare different electroencephalography (EEG)-based regressors and their
      ability to predict the simultaneously recorded blood oxygenation level dependent
      response during blocked visual stimulation, simultaneous EEG-functional magnetic
      resonance imaging in 10 healthy volunteers was performed. The performance of
      different single-trial EEG regressors was compared in terms of predicting the
      measured blood oxygenation level dependent response. The EEG-based regressors
      were the amplitude and latency of the primary positive (P1) and negative (N2)
      peaks of the visual evoked potential, the combined P1-N2 amplitude, and the alpha
      power. Apart from peak latencies, all regressors showed significant positive or
      negative correlation with the blood oxygenation level dependent response in
      visual cortex. In addition, several EEG-based regressors were found to predict
      blood oxygenation level dependent variations in different occipital and
      extraoccipital cortical areas not explained by the boxcar regressor. The results
      suggest that the P1-N2 regressor is the best EEG-based regressor to model the
      visual paradigm, but when looking for additional effects like habituation or
      attention modulation that cannot be modeled by the boxcar regressor, it is better
      to include regressors based on individual peaks or alpha power.

PMID- 22144292
TI  - Chiral ionic liquids: a compendium of syntheses and applications (2005-2012).
AB  - In recent years, the field of chiral ionic liquids (CILs) has undergone
      exponential growth. As the technology has advanced, new ways of synthesizing
      stable and structurally diverse ionic liquids have been established. This has led
      to heretofore unknown applications of CILs as well as in improving efficiency of
      previously identified applications. In this review article we have compiled a
      comprehensive database containing structures and physical properties of notable
      CILs that have been synthesized during the last 6 years. Their applications in
      the fields of asymmetric organic synthesis, spectroscopy, and chromatography are
      also illustrated. This is an expansion of our previous review, which covered the
      literature before 2005.

PMID- 22144293
TI  - In vivo enhancement in bioavailability of atazanavir in the presence of proton
      pump inhibitors using mesoporous materials.

PMID- 22144294
TI  - Modulation of human memory T-cell function by different antigen-presenting cells.

PMID- 22144295
TI  - Decoding genomes at high speed: implications for science and medicine.
AB  - At warp speed: The speed and cost of sequencing DNA has undergone tremendous
      improvement based on Solexa sequencing. This technique arose from basic curiosity
      driven research and unexpected outcomes, rather than from ideas that were
      strategically driven. The whole-genome sequencing of individuals now possible may
      one day transform the way medical disorders are classified, diagnosed, and
      treated.

PMID- 22144296
TI  - Astrocytes: multitalented stars of the central nervous system.
AB  - Astrocytes contribute to virtually every aspect of brain function, including
      ionic homeostasis, energy metabolism, and synaptic signaling. The varied and
      important roles of astrocytes have evolved to allow increasingly complex nervous
      systems to operate efficiently and with high fidelity. For example, astrocytes
      figure prominently in glutamatergic synaptic transmission, an elemental event of
      brain function: high-affinity glutamate uptake into astrocytes improves the
      temporal and spatial fidelity of glutamatergic signaling and astrocytes
      subsequently shuttle glutamine back to neurons for the synthesis of more
      glutamate. The important and dynamic contributions of astrocytes to normal brain
      function demand that the interactions between neurons and astrocytes be viewed as
      a "partnership," a harmonious collaboration to produce a desired function. The
      historical view of astrocytes as simple "support cells" is no longer valid and
      should be discarded. It is more accurate to view astrocytes as "partner cells."
      Future investigations of the intimate neuron-astrocyte partnership will require
      stringent and novel methodologies. This timely book on methodological approaches
      for studying astrocytes will provide modern neuroscientists with indispensable
      technical advice to help unravel the mysteries of the beautiful and successful
      marriage between astrocytes and neurons.

PMID- 22144297
TI  - Neurogenic astrocytes and their glycoconjugates: not just "glue" anymore.
AB  - Cells with certain attributes of very immature astroglial cells and their radial
      precursors can act as stem and/or progenitor cells during developmental and
      persistent neurogenesis. Neural stem/progenitor cells both express and are
      affected by a variety of developmentally regulated macromolecules and growth
      factors, and such signaling or recognition molecules are being uncovered through
      extensive genomic and proteomic studies, as well as tested using in vitro/in vivo
      cell growth bioassays. Glycosylated molecules are appreciated as distinct
      signaling molecules during morphogenesis in a variety of tissues and organs, with
      glycoconjugates (glycoproteins, glycolipids, and glycosaminoglycans) serving as
      mediators for the interactions of cells with each other and their substrates, to
      confer growth and differentiation cues to precursor cells in search of identity.
      Neurogenic astrocytes and associated glycoconjugates, especially extracellular
      matrix molecules, are discussed in the context of neurogenesis and
      stem/progenitor cell growth, fate choice, and differentiation.

PMID- 22144299
TI  - Preparation of mixed glial cultures from postnatal rat brain.
AB  - We describe a method to prepare postnatal rat brain primary cell cultures
      composed of astrocytes, oligodendrocytes, and microglia. After 1 week in vitro,
      the mixed glial cell cultures are free of neurons, meningeal cells and
      fibroblasts. We developed a simple procedure to selectively harvest enriched
      populations of each of the three major glial cell types. Because these cells are
      at a progenitor/immature stage, each can be further cultured separately in serum
      or serum-free media to yield large quantities of the desired glial cell
      subpopulations with a high degree of purity in the range of 96-99%. These cell
      culture models have been used extensively for performing biochemical, molecular,
      and pharmacological studies using standard assays and obtain sound quantitative
      data. These studies have given us insights into the development, properties, and
      functions of rat and mouse glial cells in vitro. The findings have largely been
      validated and extended in animal models over the last 3 decades. Since this
      method has been cited in more than 2,500 research papers, the data obtained
      across laboratories can be compared more readily.

PMID- 22144300
TI  - Generation of primary astrocyte cultures devoid of contaminating microglia.
AB  - Microglia, resident phagocytic cells of the central nervous system, are frequent
      contaminants of astrocyte cultures. Unfortunately and not always fully
      appreciated, contamination by microglia can confound results of studies designed
      to elucidate the molecular mechanisms underlying astrocyte-specific responses.
      The paradigm described herein employs the mitotic inhibitor, cytosine beta-D: 
      arabinofuranoside, followed by the lysosomotropic agent, leucine methylester, to
      maximally deplete microglia, thereby generating highly enriched astrocyte
      monolayers that remain viable and functional. Successful removal of microglia
      from confluent monolayers of primary astrocyte cultures is achieved without the
      need for cell passage and successful reduction is confirmed by depletion of
      microglial-specific markers.

PMID- 22144301
TI  - Derivation of microglia-free astrocyte cultures from neural stem cells.
AB  - Astrocytes play fundamental roles in the establishment and maintenance of tissue
      homeostasis in the central nervous system (CNS). To examine these different
      functions in vitro, it is important to be able to generate pure astrocyte
      cultures. While many "enriched" astrocyte cultures have been described, these are
      complicated by the presence of other contaminating cell types, such as microglia.
      In this chapter, we describe a method in which microglia-free astrocyte cultures
      are generated from neurospheres and also include an immunocytochemical approach
      to demonstrate the purity of these cultures.

PMID- 22144298
TI  - Heterogeneity of astrocytic form and function.
AB  - Astrocytes participate in all essential CNS functions, including blood flow
      regulation, energy metabolism, ion and water homeostasis, immune defence,
      neurotransmission, and adult neurogenesis. It is thus not surprising that
      astrocytic morphology and function differ between regions, and that different
      subclasses of astrocytes exist within the same brain region. Recent lines of work
      also show that the complexity of protoplasmic astrocytes increases during
      evolution. Human astrocytes are structurally more complex, larger, and propagate
      calcium signals significantly faster than rodent astrocytes. In this chapter, we
      review the diversity of astrocytic form and function, while considering the
      markedly expanded roles of astrocytes with phylogenetic evolution. We also define
      major challenges for the future, which include determining how astrocytic
      functions are locally specified, defining the molecular controls upon astrocytic
      fate and physiology and establishing how evolutionary changes in astrocytes
      contribute to higher cognitive functions.

PMID- 22144303
TI  - Isolation and culture of astrocytes from the retina and optic nerve.
AB  - Detailed methods for the preparation of optic nerve head (ONH) astrocytes from
      human donor eyes and retinal astrocytes from rat eyes are described. Included is
      the immunopanning method used for ONH astrocyte isolation as well as cell
      characterization. The isolation of purified retinal astrocytes is outlined as a
      method applicable to rodent and other mammalian retinas.

PMID- 22144302
TI  - Isolation and culture of spinal cord astrocytes.
AB  - Astrocytes are possibly the most numerous cells of the vertebrate central nervous
      system, yet a detailed characterization of their functions is still missing. One
      potential reason for the obscurity of astrocytic function is that they represent
      a diverse population of cells that all share some critical characteristics. In
      the CNS, astrocytes have been proposed to perform many functions. For example,
      they are supportive cells that provide guidance to newly formed migrating neurons
      and axons. They regulate the functions of endothelial cells at the blood brain
      barrier, provide nutrients, and maintain homeostasis including ionic balance
      within the CNS. More recently, dissecting the central role of astrocytes in
      mediating injury responses in the CNS, particularly the spinal cord, has become
      an area of considerable importance. The ability to culture-enriched populations
      of astrocytes has facilitated a detailed dissection of their potential roles in
      the developing and adult, normal, and injured brain and spinal cord. Most
      importantly, in vitro models have defined molecular signals that may mediate or
      regulate astrocyte functions and the capacity to modulate these signals may
      provide new opportunities for therapeutic intervention after spinal cord injury
      and other neural insults.

PMID- 22144304
TI  - Primary cultures of astrocytes from fetal bovine brain.
AB  - We describe here a method to obtain primary cell cultures from the cerebral
      cortex and the hypothalamus of bovine fetuses. We report how tissue origin,
      developmental stages, and culture medium conditions influence cell
      differentiation and the prevalence of glial cells vs. neurons. We compare
      explants from early, middle, and late stages of development and two different
      fetal calf serum concentrations (1 and 10%) to identify the best conditions to
      obtain and grow viable astrocytes in culture. In addition, we describe how to
      cryopreserve and obtain viable cortical astrocytes from frozen fetal bovine brain
      samples.

PMID- 22144305
TI  - Isolation and cultivation of porcine astrocytes.
AB  - A procedure for the isolation and cultivation of astrocytes from swine is
      described. More specifically, the donor animals are adolescent minipigs about 3
      months in age and 10 kg in weight. About 20 g of cerebral tissue can be isolated
      from the piglet, yielding enough astrocytes of homogeneous genetics for
      experimentation after only one passage in culture. The astrocyte isolation
      procedure includes mechanical and enzymatic digestion of the brain tissue
      followed by separation of the brain fragments, based on size and density.
      Astrocytes are further purified from any residual nonastrocytes by differential
      attachment during the first passage. The resulting culture is purely astrocytes
      (>98%) based upon their appearance in phase-contrast microscopy and their uniform
      expression of glial fibrillary acidic protein. More importantly for our purposes,
      the astrocytes greatly enhanced the functionality of our in vitro blood-brain
      barrier model when cocultured with porcine brain capillary endothelial cells.

PMID- 22144306
TI  - Isolation and culture of human astrocytes.
AB  - Although rodent models have been essential to unveil the emerging functions of
      astrocytes, the existence of interspecies differences calls for caution in
      extrapolating data from rodent to human astrocytes. We have developed highly
      enriched primary astrocyte cultures from human fetuses and adult cerebro-cortical
      biopsies from neurosurgery patients. Immunocytochemical characterization shows
      that cultures are composed of more than 95% of cells expressing in vitro
      astrocytic markers. Examination of the morphological and proliferative properties
      of cultures derived from the cerebral cortex and the hypothalamus both in
      untreated conditions and after treatment with EGF-related ligands illustrates the
      high plasticity of human astrocytes and their functional heterogeneity according
      to the cerebral region of origin. Our preparation offers the opportunity to
      characterize human astrocyte functions in vitro and also provides a valuable tool
      for studying the functional heterogeneity of human astrocytes isolated from
      distinct brain regions.

PMID- 22144307
TI  - Cell culturing of Caenorhabditis elegans glial cells for the assessment of
      cytosolic Ca2+ dynamics.
AB  - Cell culture has emerged as an important research method for studying various
      types of primary cells, including neurons and glial cells. This method has been
      especially instrumental in assessing intracellular Ca(2+) dynamics of neural
      cells. The invertebrate model organism Caenorhabditis elegans has been
      extensively used in neurobiology to study wide-spread issues ranging from gene
      regulation to behavior. We present some of the basic morphological
      characteristics of the four C. elegans glial cells residing in the cephalic
      sensilla of the worm, followed by a description of cell culturing methods for
      these glial cells. We describe the combined genetic and fluorescence microscopy
      approaches for identification of C. elegans glial cells in culture and assessment
      of their cytosolic Ca(2+) dynamics.

PMID- 22144308
TI  - Astrocyte polarization and wound healing in culture: studying cell adhesion
      molecules.
AB  - Astrocytes are highly polarized cells. This is manifest not only during
      development and in the adult brain, but also following injury. In response to a
      wound, astrocytes extend processes that participate in formation of a glial scar,
      which walls off lesions in the brain or spinal cord. Similarly, astrocytes in
      culture polarize dramatically and extend processes towards a scrape wound. This
      simple assay has allowed much progress in understanding the cellular events and
      molecular pathways in astrocyte polarization (1). Cell adhesion is essential for
      the early response to the wound, both with respect to process extension and cell
      polarization. This is evident in the involvement of members of the integrin
      family of cell adhesion molecules at the leading edge of the wounded astrocyte.
      Understanding the cellular and molecular bases of these events is likely relevant
      to astrocyte function during development (radial glia) as well as in wound
      healing.

PMID- 22144309
TI  - An in vitro trauma model to study rodent and human astrocyte reactivity.
AB  - Protocols are presented describing a unique in vitro injury model and how to
      culture and mature mouse, rat, and human astrocytes for its use. This injury
      model produces widespread injury and astrocyte reactivity that enable
      quantitative measurements of morphological, biochemical, and functional changes
      in rodent and human reactive astrocytes. To investigate structural and molecular
      mechanisms of reactivity in vitro, cultured astrocytes need to be purified and
      then in vitro "matured" to reach a highly differentiated state. This is achieved
      by culturing astrocytes on deformable collagen-coated membranes in the presence
      of adult-derived horse serum (HS), followed by its stepwise withdrawal. These in
      vitro matured, process-bearing, quiescent astrocytes are then subjected to
      mechanical stretch injury by an abrupt pressure pulse from a pressure control
      device that briefly deforms the culture well bottom. This inflicts a measured
      reproducible, widespread strain that induces reactivity and injury in rodent and
      human astrocytes. Cross-species comparisons are possible because mouse, rat, and
      human astrocytes are grown using essentially the same in vitro treatment regimen.
      Human astrocytes from fetal cerebral cortex are compared to those derived from
      cortical biopsies of epilepsy patients (ages 1-12 years old), with regard to
      growth, purity, and differentiation. This opens a unique opportunity for future
      studies on glial biology, maturation, and pathology of human astrocytes.
      Prototypical astrocyte proteins including GFAP, S100, aquaporin4, glutamate
      transporters, and tenascin are expressed in mouse, rat, and human in vitro
      matured astrocyte. Upon pressure-stretching, rodent and human astrocytes undergo
      dynamic morphological, gene expression, and protein changes that are
      characteristic for trauma-induced reactive astrogliosis.

PMID- 22144310
TI  - Use of gel zymography to examine matrix metalloproteinase (gelatinase) expression
      in brain tissue or in primary glial cultures.
AB  - Glia synthesize, package, and secrete several species of matrix proteases,
      including the gelatinases (pro-)MMP-2 and (pro-)MMP-9. In appropriate settings
      (e.g., experimental ischemia), these MMPs can be assayed from cerebral tissues or
      from astrocytes and microglia in culture by enzymatic substrate-dependent assays
      and by gelatin-based zymography. We describe the methodologies for the sensitive
      quantitative development of the inactive and active forms of both MMP-2 and MMP-9
      from tissues and cells, by means of lysis of the collagen substrate in collagen
      impregnated gel electropheresis by the zymogen and active gelatinases. These
      methodologies are a refinement of those used commonly, with instructions to
      increase sensitivity. Serious and often overlooked issues regarding sources of
      sample contamination and elements confounding the MMP band development and their
      interpretation are discussed.

PMID- 22144311
TI  - ELISA methodology to quantify astrocyte production of cytokines/chemokines in
      vitro.
AB  - Astrocytes are intimately involved in immunological and inflammatory events
      occurring in the central nervous system (CNS), due to their ability to secrete
      and respond to a large number of immunoregulatory cytokines/chemokines such as IL
      1beta, IL-6, IL-8, IL-10, IL-17, IL-27, TNF-alpha, TGF-beta, IFN-gamma, IFN-beta,
      CCL2, CCL3, CCL5, CXCL10, and CXCL12. Although expression of cytokines and
      chemokines is limited in the normal CNS, elevated expression of these proteins,
      as seen in disease entities such as multiple sclerosis (MS), HIV-1 associated
      neurocognitive disorders (HAND), Alzheimer's disease (AD), Parkinson's disease
      (PD) and amyotrophic lateral sclerosis (ALS), contributes to the development of
      inflammation and neuronal demise in these diseases. As a potent source of
      cytokines and chemokines, astrocytes play a pivotal role in the type and extent
      of neuroinflammatory responses. Astrocytes can be stimulated in vitro to produce
      numerous cytokines/chemokines, which are secreted and detected in supernatants by
      a technique known as enzyme-linked immunosorbent assay (ELISA). In this chapter,
      we describe our experience using ELISAs to detect and quantify cytokines and
      chemokines secreted by stimulated murine astrocytes, specifically IL-6 and
      CXCL10.

PMID- 22144313
TI  - Examining potassium channel function in astrocytes.
AB  - Electrophysiologically, astrocytes are characterized by a high K(+) resting
      conductance and a hyperpolarized resting membrane potential. Both features are
      due to the activity of astrocytic potassium channels. Astrocytes express a
      variety of voltage-dependent and leak potassium channels on the plasma membrane
      that contribute to the hyperpolarized resting membrane potential and other
      cellular processes. This chapter focuses on measuring K(+) channel function in
      astrocytes, focusing on Kir4.1, an inwardly rectifying potassium channel. We and
      others have demonstrated that Kir4.1 contributes significantly to the high
      resting K(+) conductance and the hyperpolarized resting membrane potential. This
      channel is also implicated in channel-mediated regulation of extracellular
      potassium.

PMID- 22144312
TI  - Induction of nitric oxide synthase-2 expression and measurement of nitric oxide
      production in enriched primary cortical astrocyte cultures.
AB  - Astrocytes produce numerous mediators under conditions of inflammation in the
      central nervous system. One such mediator is nitric oxide (NO) derived from
      nitric oxide synthase-2 (NOS-2), the high output, inducible NOS isoform.
      Expression of NOS-2 and production of NO can be stimulated in astrocyte cultures
      by combinations of cytokines and lipopolysaccharide, a gram-negative bacterial
      endotoxin. This chapter details methods to induce and analyze NOS-2 expression
      and NO production in astrocyte cultures.

PMID- 22144314
TI  - Connexin-based channels in astrocytes: how to study their properties.
AB  - A typical feature of astrocytes is their high level of connexin expression. These
      membrane proteins constitute the molecular basis of two types of channels: gap
      junction channels that allow direct cytoplasm-to-cytoplasm communication and
      hemichannels that provide a pathway for exchanges between the intra- and
      extracellular media. An unusual property of these channels is their permeability
      for ions but also for small signaling molecules. They support intercellular
      communication that contribute to dynamic neuroglial interaction and interplay
      with neuronal activity and survival. Here, we describe multiple techniques based
      either on electrophysiological approaches or the monitoring of dye intercellular
      diffusion and uptake that permits an investigation of the properties of gap
      junction channels and hemichannels, respectively. These techniques are applied in
      astrocyte studies using in vitro models, mainly primary cultures and acute brain
      slices.

PMID- 22144315
TI  - Isotope-based quantitation of uptake, release, and metabolism of glutamate and
      glucose in cultured astrocytes.
AB  - Protocols are described for measurement in primary cultures of astrocytes of
      unidirectional fluxes of glutamate (influx and efflux), glutamate metabolism to
      glutamine or CO(2), glucose influx, glycolysis, pyruvate dehydrogenation,
      oxidative metabolism of glucose, pyruvate carboxylation, glycogen synthesis, and
      glycogenolysis. References are made to the in vivo situation, and the importance
      of using metabolically competent cultures is emphasized.

PMID- 22144316
TI  - An in vitro model of reactive astrogliosis and its effect on neuronal growth.
AB  - Astrogliosis, whereby astrocytes in the central nervous system (CNS) become
      reactive in response to tissue damage, is a prominent process leading to the
      formation of the glial scar that inhibits axon regeneration after CNS injury.
      Upon becoming reactive, astrocytes undergo various molecular and morphological
      changes including upregulating their expression of GFAP and chondroitin sulfate
      proteoglycans (CSPGs) as well as other molecules that are inhibitory to axon
      growth. We have developed an in vitro model of reactive astrogliosis as a result
      of treating cultured astrocytes with transforming growth factor-beta (TGF-beta),
      which induces increased expression as well as secretion of CSPGs. These reactive
      astrocytes show inhibitory effects on neuron growth both in neuron-astrocyte
      coculture and in neurite guidance spot assay using astrocyte-conditioned medium.
      These reactive astrocytes provide a vehicle for testing substances that might
      overcome the glial scar and promote regeneration.

PMID- 22144317
TI  - A neuron-astrocyte co-culture system to investigate astrocyte-secreted factors in
      mouse neuronal development.
AB  - Astrocytes secrete factors that promote neuron survival, synapse formation, and
      plasticity. Understanding how these factors perform these roles requires a robust
      in vitro system that can effectively assess the impact of individual glial
      factors on neuronal properties. A classical approach to studying neuron-glial
      interactions in vitro uses a system where dissociated embryonic rat neurons are
      suspended over a feeder layer of rat astrocytes. Here, we describe a useful
      "sandwich" co-culture system where postnatal mouse hippocampal neurons are grown
      suspended above a feeder layer of mouse hippocampal astrocytes. We demonstrate
      that neurons in these cultures remain healthy beyond 3 weeks in vitro and develop
      more synapses compared to neurons grown without astrocytes. An advantage of this
      method is that astrocytes and neurons can be prepared separately from postnatal
      transgenic or knock-out mouse lines allowing one to study, for example, how wild
      type neurons develop in the presence of astrocytes from a knock-out mouse line
      that lacks the expression of a specific astrocyte-secreted factor. We find this
      culture system to be a convenient and powerful approach to study the contribution
      of astrocyte-secreted molecules to neuron development.

PMID- 22144318
TI  - Cocultures of neurons and astrocytes as a model for examining hypoxia-induced
      neuronal death.
AB  - Astrocytes perform critical functions necessary for neuronal survival. Thus,
      examining the influence of astrocyte function on neuronal cell death during
      disease, including hypoxia/ischemia, has become an important avenue of
      investigation. In this chapter we detail the methodology and potential pitfalls
      for establishing cocultures of astrocytes and cortical neurons for studying
      hypoxia-induced neuronal death. In brief, astrocyte cultures are first
      established until they reach confluence. The medium is exchanged from a medium
      that supports astrocyte growth to a medium that supports neuronal viability 24 h
      before adding neurons to the astrocyte monolayer. After the neurons mature, the
      cultures are exposed to severe hypoxia and neuronal death is quantified 1-2 days
      later.

PMID- 22144319
TI  - Use of astrocyte-microglial cocultures to examine the regulatory influence of
      astrocytes on microglial activation.
AB  - Microglia are the principal immune effector cells of the central nervous system
      (CNS). Under normal conditions, they occupy a quiescent surveillance phenotype,
      but following stimulation by microorganisms or inflammatory cytokines, microglia
      transform into highly activated migratory, phagocytic cells producing
      inflammatory cytokines and chemokines. Significantly, several studies have
      demonstrated that astrocytes attenuate microglial activation, reducing microglial
      adhesion, production of interleukin-12 (IL-12) and reactive oxygen species (ROS),
      and expression of inducible nitric oxide synthase (iNOS). In this chapter, we
      describe an astrocyte-microglia coculture system that can be used to investigate
      interactions between these two cell types. We also describe a flow cytometry
      approach to quantify microglial activation state, as assessed by microglial
      expression of cellular activation markers, including MHC class I and the Mac-1
      and alpha4 integrins.

PMID- 22144320
TI  - Astrocyte-Schwann-cell coculture systems.
AB  - Schwann cells are one of the cellular candidates used in repair strategies
      following trauma and demyelination of the spinal cord. One of the major obstacles
      in the use of Schwann cells is their limited migratory ability within the
      astrocytic environment of the CNS and boundary formation between the Schwann
      cells of the graft and the host astrocytes. This boundary creates an abrupt
      obstacle for regenerating axons attempting to exit the Schwann cell graft back to
      the CNS. To facilitate the study of mechanisms underlying these interactions, in
      vitro coculture assays of Schwann-Astrocytes have been developed. In this
      chapter, we have described the methodology for two commonly used coculture
      systems known as the Schwann-Astrocyte boundary assay and the inverted coverslip
      migration assay.

PMID- 22144321
TI  - An in vitro assay to examine oligodendrocyte precursor cell migration on
      astrocytes.
AB  - Oligodendrocyte migration is required for the myelination of axons during
      development and also following demyelinating lesions of the central nervous
      system. Oligodendrocytes arise from oligodendrocyte precursor cells (OPCs) which
      are present within the brain and spinal cord. To reach the demyelinating lesions,
      OPCs have to migrate through a dense meshwork of inhibitory astrocytes.
      Therefore, interactions between these two cell types are of great importance in
      myelination. To facilitate the study of mechanisms underlying these interactions,
      in vitro co-culture assays of oligodendrocyte-astrocytes have been developed. In
      this chapter we describe the methodology for a co-culture system known as the
      inverted coverslip migration assay, which has been used to study the effect of
      astrocytes on oligodendrocyte migratory behaviour.

PMID- 22144322
TI  - Investigation of astrocyte - oligodendrocyte interactions in human cultures.
AB  - Multiple sclerosis (MS) is characterized by CNS demyelination and oligodendrocyte
      depletion, axonal loss, and reactive astrogliosis. Myelin loss causes conduction
      block, while remyelination is associated with recovery of conduction and return
      of function. Reactive astrocytes are a prominent feature of MS plaques, and have
      been implicated as producing factors regulating oligodendrocyte progenitor
      differentiation and myelin formation. Understanding their impact on these events
      may lead to new approaches for oligodendrocyte protection and/or remyelination in
      MS. Here, we outline protocols for the establishment and analysis of primary
      monocultures and cocultures of human astrocytes and oligodendrocytes. These
      approaches are designed to facilitate analysis of mechanisms underlying
      astrocytic regulation of progenitor survival and myelin repair.

PMID- 22144323
TI  - An improved in vitro blood-brain barrier model: rat brain endothelial cells co
      cultured with astrocytes.
AB  - In vitro blood-brain barrier (BBB) models using primary cultured brain
      endothelial cells are important for establishing cellular and molecular
      mechanisms of BBB function. Co-culturing with BBB-associated cells especially
      astrocytes to mimic more closely the in vivo condition leads to upregulation of
      the BBB phenotype in the brain endothelial cells. Rat brain endothelial cells
      (RBECs) are a valuable tool allowing ready comparison with in vivo studies in
      rodents; however, it has been difficult to obtain pure brain endothelial cells,
      and few models achieve a transendothelial electrical resistance (TEER, measure of
      tight junction efficacy) of >200 Omega cm(2), i.e. the models are still
      relatively leaky. Here, we describe methods for preparing high purity RBECs and
      neonatal rat astrocytes, and a co-culture method that generates a robust, stable
      BBB model that can achieve TEER >600 Omega cm(2). The method is based on >20
      years experience with RBEC culture, together with recent improvements to kill
      contaminating cells and encourage BBB differentiation.Astrocytes are isolated by
      mechanical dissection and cell straining and are frozen for later co-culture.
      RBECs are isolated from 3-month-old rat cortices. The brains are cleaned of
      meninges and white matter and enzymatically and mechanically dissociated.
      Thereafter, the tissue homogenate is centrifuged in bovine serum albumin to
      separate vessel fragments from other cells that stick to the myelin plug. The
      vessel fragments undergo a second enzyme digestion to separate pericytes from
      vessels and break down vessels into shorter segments, after which a Percoll
      gradient is used to separate capillaries from venules, arterioles, and single
      cells. To kill remaining contaminating cells such as pericytes, the capillary
      fragments are plated in puromycin-containing medium and RBECs grown to 50-60%
      confluence. They are then passaged onto filters for co-culture with astrocytes
      grown in the bottom of the wells. The whole procedure takes ~2 weeks, using pre
      frozen astrocytes, from isolation of RBECs to generation of high-resistance/low
      permeability RBEC monolayers.

PMID- 22144324
TI  - In vitro models of the blood-brain barrier.
AB  - The chapter provides an introduction and brief overview of currently available in
      vitro blood-brain barrier models, pointing out the major advantages and
      disadvantages of the respective models and potential applications. Bovine brain
      microvessel endothelial cell isolation, culture, and transendothelial
      permeability measurement procedures are discussed in detail as a model system for
      a laboratory to begin brain vascular investigations.

PMID- 22144325
TI  - An in vitro model of ischemic stroke.
AB  - Brain stroke is a devastating cerebrovascular disease and ranks as the third most
      common cause of death and disability in the US. Altered blood-brain barrier (BBB)
      signaling and permeability characteristics during stroke can increase the risk
      for life-threatening hemorrhagic transformation or damaging brain edema. The BBB
      plays a crucial role in maintaining the permeability and CNS homeostasis under
      physiological/pathological conditions by protecting the brain from the
      fluctuations in plasma constituents. Many in vitro brain endothelial cell culture
      models have been developed and studied over the past several decades to
      understand the pathophysiological mechanisms and role of the BBB in stroke.
      Restrictive barrier properties of brain endothelial cells have been shown to be
      predominantly influenced by astrocytes and astrocyte-secreting factors using
      coculture systems. By using astrocyte-endothelial cocultures, it is possible to
      model in vivo BBB characteristics, while allowing for mechanistic studies to be
      performed. Hence, the application of in vitro astrocyte-endothelial coculture BBB
      systems is a powerful technique to understand and investigate the
      pathophysiological mechanisms in stroke. This approach can be utilized to uncover
      cell signaling pathways and that may identify new neurovascular drug targets to
      treat this devastating brain vascular disease.

PMID- 22144326
TI  - Pericyte coculture models to study astrocyte, pericyte, and endothelial cell
      interactions.
AB  - The microvascular pericyte is an integral component of the blood-brain barrier
      and the neurovascular unit. Most model systems that have been developed to study
      the functional parameters of these systems have not incorporated the pericyte. In
      this chapter, we consider pericyte coculture and triple culture systems and
      detail the methodology, suggestions, and problems with isolation of these unique
      cells. We also present data to show that triple cultures are ideal to study the
      role of the CNS pericyte in CNS angiogenesis.

PMID- 22144327
TI  - Reprogramming of postnatal astroglia of the mouse neocortex into functional,
      synapse-forming neurons.
AB  - Direct conversion of glia into neurons by cellular reprogramming represents a
      novel approach toward a cell-based therapy of neurodegenerative processes. Here
      we describe a protocol that allows for the direct and efficient in vitro
      reprogramming of mouse astroglia from the early postnatal neocortex by forced
      expression of single neurogenic fate determinants. By selective retrovirus
      mediated expression of neurogenin-2 (Neurog2) on the one hand, or the mouse
      homologue of Distal-less Dlx2 or the mammalian homologue of achaete-schute-1
      (Mash1) on the other, it is possible to drive postnatal astroglia in culture
      toward the genesis of fully functional, synapse-forming, glutamatergic, i.e.,
      excitatory, and GABAergic, i.e., inhibitory, neurons, respectively.

PMID- 22144329
TI  - Imaging in vivo astrocyte/endothelial cell interactions at the blood-brain
      barrier.
AB  - The goal of this chapter is to highlight methods used to demonstrate in vivo
      changes in astrocyte expression at the blood-brain barrier (BBB). Loss of BBB
      integrity is seen in many acute and chronic disease conditions. However, despite
      the importance of the BBB to homeostasis and correct functioning of the CNS, the
      nature of factors responsible for the induction and maintenance of BBB properties
      in development and the adult remains unclear. We have studied the role of
      astrocytes in modulating BBB integrity in two in vivo models using a gliotoxin (3
      chloropropanediol), and under hypoxic stress. 3-chloropropanediol-induced
      astrocytic loss within the inferior colliculus leads to loss of endothelial tight
      junction protein expression and loss of BBB integrity. As glial fibrillary acidic
      protein (GFAP)-immunopositive astrocytes repopulated the lesion, tight junction
      protein expression returned to paracellular domains and BBB integrity was
      restored. Under hypoxic conditions, increased GFAP expression was seen with
      changes in tight junction protein expression and loss of BBB integrity. These
      studies suggest a critical role for glial/endothelial interactions in regulating
      BBB integrity in health and disease.

PMID- 22144328
TI  - Assessment of glial function in the in vivo retina.
AB  - Glial cells, traditionally viewed as passive elements in the CNS, are now known
      to have many essential functions. Many of these functions have been revealed by
      work on retinal glial cells. This work has been conducted almost exclusively on
      ex vivo preparations and it is essential that retinal glial cell functions be
      characterized in vivo as well. To this end, we describe an in vivo rat
      preparation to assess the functions of retinal glial cells. The retina of
      anesthetized, paralyzed rats is viewed with confocal microscopy and laser speckle
      flowmetry to monitor glial cell responses and retinal blood flow. Retinal glial
      cells are labeled with the Ca(2+) indicator dye Oregon Green 488 BAPTA-1 and the
      caged Ca(2+) compound NP-EGTA by injection of the compounds into the vitreous
      humor. Glial cells are stimulated by photolysis of caged Ca(2+) and the
      activation state of the cells assessed by monitoring Ca(2+) indicator dye
      fluorescence. We find that, as in the ex vivo retina, retinal glial cells in vivo
      generate both spontaneous and evoked intercellular Ca(2+) waves. We also find
      that stimulation of glial cells leads to the dilation of neighboring retinal
      arterioles, supporting the hypothesis that glial cells regulate blood flow in the
      retina. This in vivo preparation holds great promise for assessing glial cell
      function in the healthy and pathological retina.

PMID- 22144330
TI  - Transgenic techniques for cell ablation or molecular deletion to investigate
      functions of astrocytes and other GFAP-expressing cell types.
AB  - Genetic tools are enabling the molecular dissection of the functions and
      mechanisms of many biological processes. Transgenic manipulations provide
      powerful tools with which to test hypotheses regarding functions of specific cell
      types and molecules in vivo in combination with different types of experimental
      models. Various techniques are available that can target genetic manipulations
      specifically to astrocytes and that are enabling the molecular dissection of
      astrocyte biology in vivo. This article summarizes procedures and experience from
      our laboratory using transgenic strategies that enable either the ablation of
      proliferating astrocytes and related cells, or the deletion of specific molecules
      selectively from astrocytes, to study the functions of astrocytes and related
      cell types in health and disease in vivo using different experimental mouse
      models.

PMID- 22144331
TI  - In vivo imaging of Ca2+ signaling in astrocytes using two-photon laser scanning
      fluorescent microscopy.
AB  - Astrocytes are the predominant nonneuronal cell type in the central nervous
      system. Although they are electrically nonexcitable, they have been found to play
      an active role in modulation of neuronal function and plasticity through Ca(2+)
      excitability. Thus, Ca(2+) signaling in astrocytes serves as a mediator of
      bidirectional interactions between neurons and astrocytes. Although astrocytic
      Ca(2+) signaling has been extensively studied in cultured cells, the recent
      development of two-photon laser scanning fluorescent microscopy and astrocyte
      specific dye labeling make it possible to study astrocytic Ca(2+) signaling in
      live animals. Here we describe a detailed protocol for in vivo Ca(2+) imaging of
      astrocytes in mice.

PMID- 22144332
TI  - Use of Cre-lox technology to analyze integrin functions in astrocytes.
AB  - Astrocytes communicate with the vascular endothelium via direct cell-cell
      contacts as well as a variety of secreted growth factors and extracellular matrix
      (ECM) proteins. Integrins are heterodimeric cell surface receptors for ECM
      protein ligands, and many integrin subunits are expressed in astrocytes. Here, we
      will discuss gene deletion strategies in mice that have deciphered functions for
      specific integrins in astrocyte-endothelial cell adhesion and signaling.
      Specifically, we will detail how Cre-lox molecular genetic techniques have
      revealed important roles for integrin alphavbeta8 in regulating cerebral blood
      vessel development and homeostasis. First, we will detail how to generate Cre-lox
      mutant mouse models that our group and others have used to study alphavbeta8
      integrin in embryonic astroglial progenitors and postnatal astrocytes. Second, we
      will discuss how viral-delivered Cre can be used to acutely delete integrin genes
      in astrocytes within defined anatomic regions of the brain. Third, detailed in
      vivo methods to verify Cre-mediated gene recombination in astrocytes will be
      presented. Lastly, we will present one experimental strategy to determine how
      integrin gene deletion affects astrocyte-endothelial cell coupling in the CNS.
      While this review focuses on the generation and characterization of mice lacking
      alphavbeta8 integrin, these experimental strategies can be expanded to analyze
      other cell adhesion and signaling genes important for astroglial-mediated
      regulation of blood vessel development and homeostasis.

PMID- 22144333
TI  - The magnetic field dependence of water T1 in tissues.
AB  - The magnetic field dependence of the composite (1)H(2)O nuclear magnetic
      resonance signal T(1) was measured for excised samples of rat liver, muscle, and
      kidney over the field range from 0.7 to 7 T (35-300 MHz) with a nuclear magnetic
      resonance spectrometer using sample-shuttle methods. Based on extensive
      measurements on simpler component systems, the magnetic field dependence of T(1)
      of all tissues studied are readily fitted at Larmor frequencies above 1 MHz with
      a simple relaxation equation consisting of three contributions: a power law,
      A*omega(-0.60) related to the interaction of water with long-lived-protein
      binding sites, a logarithmic term B*tau(d) *log(1+1/(omegatau(d))(2)) related to
      water diffusion at macromolecular interfacial regions, and a constant term
      associated with the high frequency limit of water-spin-lattice relaxation. The
      parameters A and B include the concentration and surface area dependences
      respectively. The logarithmic diffusion term becomes significant at high magnetic
      fields and is consistent with rapid translational dynamics at macromolecular
      surfaces. The data are fitted well with translational correlation times of
      approximately 15 ps for human brain white matter, but with a B value three times
      larger than gray matter tissues. This analysis suggests that the water-surface
      translational correlation time is approximately three times longer than in gray
      matter.

PMID- 22144334
TI  - Ionic and electronic transport in Ag2S nanocrystal-GeS2 matrix composites with
      size-controlled Ag2S nanocrystals.

PMID- 22144335
TI  - Biofilm formation in moderately halophilic bacteria is influenced by varying
      salinity levels.
AB  - Bacteria in a biofilm have a co-dependent lifestyle resulting in a harmonized and
      complex coordination of the bacterial cells within an exopolysaccharide (EPS)
      matrix. We hypothesized that biofilm formation and EPS production in salt
      tolerant bacteria are helpful for plant growth improvement in saline soil, but
      that they are influenced differently. To investigate this hypothesis, we tested
      the effect of different salinity levels on the biofilm formation of the bacterial
      strains PAa6 (Halomonas meridiana), HT2 (Kushneria indalinina) and ST2 (Halomonas
      aquamarina) on different abiotic and biotic surfaces. Maximum biofilm formation
      was established at 1 M salt concentration. However, EPS production was maximal at
      0-1 M NaCl stress. We also studied the effect of salt stress on EPS produced by
      the bacterial strains and confirmed the presence of EPS on Cicer arietinum var.
      CM 98 roots and in soil at different salinity levels, using Alcian blue staining.
      Overall, the strain PAa6 was more effective in biofilm formation and EPS
      production. Under saline and non-saline conditions, this strain also colonized
      the plant roots more efficiently as compared to the other two strains. We
      conclude that the strain PAa6 has the potential of biofilm formation and EPS
      production at different salinity levels. The presence of EPS in the biofilm
      helped the bacterial strains to better colonize the roots.

PMID- 22144336
TI  - Patient weight more than body mass index influences total hip arthroplasty long
      term survival.
AB  - The effect of obesity on the long-term survival of total hip arthroplasty remains
      under discussion. Reviewing meta-analyses of large cohort studies a high body
      mass index has been correlated with a higher incidence of complications but not
      univocally with a lower implant survival rate. It has been suggested that body
      weight rather than body mass index might be a better parameter to evaluate
      prosthesis outcome. We reviewed 27,571 patients retrospectively with primary
      arthritis as a preoperative diagnosis. Patients were divided into 4 categories
      based on their body mass index, or into two groups based on the body weight (<80
      kg and =80 kg). Implant survivorship was estimated with use of the Cox
      proportional hazards model with revision for aseptic loosening as the end point.
      Results were stratified for sex and implant tribology. When body mass index was
      used the 10 years implant survival in obese versus non-obese patients was not
      statistically different (p=0.058), but when body weight was used a statistically
      different implant survivorship was found for men (p=0.009). Therefore, weight
      rather than than body mass index influences survival of hip prostheses, and
      should be used as the discriminant parameter for further studies.

PMID- 22144337
TI  - A retrieval analysis of explanted Durom metal-on-metal hip arthroplasties.
AB  - Given the recent reports of high failure rates, an improved understanding of the
      mechanism of failure of large diameter metal-on-metal hip arthroplasties is
      essential. We present clinical data and tribological analysis of a consecutive
      series of 74 failed large diameter metal-on-metal hips, comparing the Durom
      (Zimmer) with the Birmingham hip resurfacing (BHR) (Smith and Nephew). We
      retrospectively analysed pre-, intra-, and post-operative clinical data and
      measured the linear wear and component form of the explanted components using a
      roundness measuring machine. A significantly higher proportion of hips in the
      Durom group failed as a result of acetabular loosening (p=0.001) and this was
      supported by evidence of reduced bone in-growth on the backside of the cup.
      Comparison of roundness measurement revealed that the Durom hip was significantly
      lower wearing than the BHR (p<0.05) but the Durom femoral components were subject
      to significantly greater form errors (p<0.001), the pole of the head being
      flattened by up to 31 microns. Although the Durom hip is low wearing, reduced
      sphericity of the femoral component may have resulted in equatorial bearing,
      leading to an increased frictional torque at the cup-bone interface, preventing
      bone in-growth, and culminating in acetabular loosening. This supports recent
      clinical findings of high revision rates as a result of acetabular loosening for
      the Durom metal-on-metal hip system.

PMID- 22144343
TI  - Natalizumab treatment perturbs memory- and marginal zone-like B-cell homing in
      secondary lymphoid organs in multiple sclerosis.
AB  - Natalizumab, an antibody against the alpha4 subunit of alpha4 integrins, has been
      approved for multiple sclerosis (MS) therapy based on its high efficacy and
      safety profile. However, natalizumab has been associated with the development of
      progressive multifocal leukoencephalopathy (PML), a disorder caused by JC virus
      (JCV) infection. In order to improve our understanding of the mechanism of action
      of natalizumab and to identify possible risk factors for PML development, we have
      characterized in detail the cell blood composition in MS patients treated with
      natalizumab for more than 30 months. Natalizumab induced the release of lymphoid-
      but not myeloid precursor cells, which resulted in a chronic increase ofT-, NK-
      and particularly B cells. While the percentage of recent thymic emigrants (RTEs),
      naiotave, effector or memory T cells remained unchanged during treatment, a
      higher percentage of memory- and marginal zone (MZ)-like, but not of naiotave B
      cells, was observed, which most likely is due to a decreased retention of these
      cells within the splenic MZ. The ability of natalizumab to influence B-cell
      migration and homeostasis through the splenic MZ, where JCV has been detected,
      adds to the list of natalizumab effects and may contribute to PML development by
      disseminating JCV.

PMID- 22144344
TI  - Synthesis of a biologically active triazole-containing analogue of cystatin A
      through successive peptidomimetic alkyne-azide ligations.

PMID- 22144345
TI  - Leptin resistance does not induce hyperphagia in the rat.
AB  - Leptin has been thought to work as a mediator for body weight control by
      inhibiting food intake. Leptin, however, cannot prevent obesity induced by a high
      fat diet (HFD) probably because of leptin resistance. We investigated daily
      feeding and weight gain when ordinary chow (OC) was changed to a HFD in male
      rats. Food intake, by weight, significantly increased the next day, but gradually
      decreased until at 20 days the HFD intake contained the same calories as consumed
      by the OC-fed control rats. The reduction in food intake occurred only during the
      night without change of preference for the HFD, even after leptin resistance had
      developed. Nonetheless, the HFD-fed rats gained more weight than the controls.
      From the present experiment, it is concluded that leptin resistance does not
      induce hyperphagia, and suggested that body weight is not regulated to be
      constant.

PMID- 22144347
TI  - Effects of mindfulness-based stress reduction on emotional experience and
      expression: a randomized controlled trial.
AB  - OBJECTIVES: Mindfulness-based stress reduction (MBSR) has been found to reduce
      psychological distress and improve psychological adjustment in medical,
      psychiatric, and nonclinical samples. We examined its effects on several
      processes, attitudes, and behavior patterns related to emotion regulation.
      DESIGN: Fifty-six adults were randomly assigned to MBSR or to a waiting list
      (WL). RESULTS: Compared with WL completers (n = 21), MBSR completers (n = 20)
      reported significantly greater increases in trait mindfulness and decreases in
      absent-mindedness, greater increases in self-compassion, and decreases in fear of
      emotions, suppression of anger, aggressive anger expression, worry, and
      difficulties regulating emotions. The WL group subsequently received MBSR, and
      the two groups combined showed significant changes on all of these variables from
      pre-MBSR to post-MBSR, and on all except the 2 anger variables from pre-test to 2
      month follow-up, as well as significant reductions in rumination. CONCLUSION: An
      8-week mindfulness training program might increase mindful awareness in daily
      life and have beneficial impact on clinically relevant emotion regulation
      processes.

PMID- 22144348
TI  - High-capacity silicon-air battery in alkaline solution.

PMID- 22144346
TI  - Selective mGluR1 antagonist EMQMCM inhibits the kainate-induced excitotoxicity in
      primary neuronal cultures and in the rat hippocampus.
AB  - Abundant evidence suggests that indirect inhibitory modulation of glutamatergic
      transmission, via metabotropic glutamatergic receptors (mGluR), may induce
      neuroprotection. The present study was designed to determine whether the
      selective antagonist of mGluR1 (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy
      cyclohexyl)-methanone methanesulfonate (EMQMCM), showed neuroprotection against
      the kainate (KA)-induced excitotoxicity in vitro and in vivo. In in vitro studies
      on mouse primary cortical and hippocampal neuronal cultures, incubation with KA
      (150 MUM) induced strong degeneration [measured as lactate dehydrogenase (LDH)
      efflux] and apoptosis (measured as caspase-3 activity). EMQMCM (0.1-100 MUM)
      added 30 min to 6 h after KA, significantly attenuated the KA-induced LDH release
      and prevented the increase in caspase-3 activity in the cultures. Those effects
      were dose- and time-dependent. In in vivo studies KA (2.5 nmol/1 MUl) was
      unilaterally injected into the rat dorsal CA1 hippocampal region. Degeneration
      was calculated by counting surviving neurons in the CA pyramidal layer using
      stereological methods. It was found that EMQMCM (5-10 nmol/1 MUl) injected into
      the dorsal hippocampus 30 min, 1 h, or 3 h (the higher dose only) after KA
      significantly prevented the KA-induced neuronal degeneration. In vivo
      microdialysis studies in rat hippocampus showed that EMQMCM (100 MUM)
      significantly increased gamma-aminobutyric acid (GABA) and decreased glutamate
      release. When perfused simultaneously with KA, EMQMCM substantially increased
      GABA release and prevented the KA-induced glutamate release. The obtained results
      indicate that the mGluR1 antagonist, EMQMCM, may exert neuroprotection against
      excitotoxicity after delayed treatment (30 min to 6 h). The role of enhanced
      GABAergic transmission in the neuroprotection is postulated.

PMID- 22144349
TI  - Screening for cellulases with industrial value and their use in biomass
      conversion.
AB  - Cellulose is an easily renewable and highly occurring resource. To take advantage
      of this great potential, there is a constant need of new cellulose degrading
      enzymes. In industrial applications enzymes have to function under extreme
      conditions like high temperature, very acidic or basic pH and different solvents.
      Cellulases have a huge area of application, for example the textile and food
      industry as well as the generation of bioethanol as an alternative energy source.
      They have the ability to yield a great energetic potential, but there is still a
      lack of economical technologies to conquer the stability of the cellulose
      structure. Via metagenomic research and well-directed screening, it is possible
      to detect new cellulases, which are active under tough industrial conditions.

PMID- 22144350
TI  - Reversal of NAD(P)H cofactor dependence by protein engineering.
AB  - There is increasing interest in utilization of engineered microorganisms for the
      production of renewable chemicals and next-generation biofuels. However,
      imbalances between the cofactor consumption of the engineered production pathway
      and the reducing equivalents provided by the cell have been shown to limit
      yields. This imbalance can be overcome by adjusting the cofactor dependencies of
      the pathway enzymes to match the available cofactors in the cell. We show how
      cofactor preference can be reversed by structure-guided directed evolution of the
      target enzyme.

PMID- 22144352
TI  - High isoprenoid flux Escherichia coli as a host for carotenoids production.
AB  - A noncarotenogenic microbe E. coli was engineered for high production of
      carotenoids. To increase the isoprenoid flux, the chromosomal native promoters of
      the rate-controlling steps (dxs, idi and ispDispF) in the isoprenoid pathway were
      replaced with a strong bacteriophage T5 promoter (P(T5)) by using the lambda-Red
      recombinase system in combination with the Flp/FRT site-specific recombination
      system for marker excision and P1 transduction for gene trait stacking. The
      resulting high isoprenoid flux E. coli can be used as a starting strain to
      produce various carotenoids by introducing heterologous carotenoid genes. In this
      study, the high isoprenoid flux E. coli was transformed with a plasmid carrying
      the beta-carotene biosynthetic genes from Pantoea stewartii for beta-carotene
      production.

PMID- 22144351
TI  - Quantifying plasmid copy number to investigate plasmid dosage effects associated
      with directed protein evolution.
AB  - Our laboratory specializes in directed protein evolution, i.e., evolution of
      proteins under defined selective pressures in the laboratory. Our target genes
      are encoded in ColE1 plasmids to facilitate the generation of libraries in vivo.
      We have observed that when random mutations are not restricted to the coding
      sequence of the target genes, directed evolution results in a strong positive
      selection of plasmid origin of replication (ori) mutations. Surprisingly, this is
      true even during evolution of new biochemical activities, when the activity that
      is being selected was not originally present. The selected plasmid ori mutations
      are diverse and produce a range of plasmid copy numbers, suggesting a complex
      interplay between ori and coding mutations rather than a simple enhancement of
      level of expression of the target gene. Thus, plasmid dosage may contribute
      significantly to evolution by fine-tuning levels of activity. Here, we present
      examples illustrating these observations as well as our methods for efficient
      quantification of plasmid copy number.

PMID- 22144353
TI  - Mutagenic Inverted Repeats Assisted Genome Engineering (MIRAGE) in Saccharomyces
      cerevisiae: deletion of gal7.
AB  - MIRAGE is a unique in vivo genome editing technique that exploits the inherent
      instability of inverted repeats (palindromes) in the Saccharomyces cerevisiae
      chromosome. As a technique able to quickly create deletions as well as precise
      point mutations, it is valuable in applications that require creation of designer
      strains of this yeast. In particular, it has various potential applications in
      metabolic engineering, systems biology, synthetic biology, and molecular
      genetics.

PMID- 22144354
TI  - Creation of new metabolic pathways or improvement of existing metabolic enzymes
      by in vivo evolution in Escherichia coli.
AB  - A method for in vivo evolution of metabolic pathways in bacteria is described.
      This method is a powerful tool for synthetic biology type of metabolic design and
      can lead to the creation of new metabolic pathways or the improvement of existing
      metabolic enzymes. The proposed strategy also permits to relate the evolved
      phenotype to the genotype and to analyze evolution phenomenon at the genetic,
      biochemical, and metabolic levels.

PMID- 22144355
TI  - Bioluminescent reporter genes for promoter discovery.
AB  - Discovery of promoter elements with previously unknown regulated responses is
      important for metabolic engineering. For example, promoters responsive to the end
      product can be useful to regulate expression with increasing levels of product.
      In addition, such promoters can be used as screens for production strain with
      increased titers. Use of reporter genes, such as a bioluminescent reporter
      luxCDABE, can facilitate promoter discovery. Here, protocols for analysis of
      genome-wide luxCDABE reporter gene collections in Escherichia coli are provided.
      Further, a protocol for using a selected para-hydroxycinnamic (pHCA)-responsive
      promoter as detection assay for bioproduced pHCA is provided.

PMID- 22144356
TI  - Recombination-based DNA assembly and mutagenesis methods for metabolic
      engineering.
AB  - In recent years there has been a growing interest in the precise and concerted
      assembly of multiple DNA fragments of diverse sizes, including chromosomes, and
      the fine tuning of gene expression levels and protein activity. Commercial DNA
      assembly solutions have not been conceived to support the cloning of very large
      or very small genetic elements or a combination of both. Here we summarize a
      series of protocols that allow the seamless, simultaneous, flexible, and highly
      efficient assembly of DNA elements of a wide range of sizes (up to hundred
      thousand base pairs). The protocols harness the power of homologous recombination
      and are performed either in vitro or within the living cells. The DNA fragments
      may or may not share homology at their ends. An efficient site-directed
      mutagenesis protocol enhanced by homologous recombination is also described.

PMID- 22144357
TI  - Ethanol-tolerant gene identification in Clostridium thermocellum using pyro
      resequencing for metabolic engineering.
AB  - Classic strain development that combines random mutagenesis and selection has a
      long history of success in generation of biocatalysts with industrially designed
      traits. However, the genetic loci contributing to the phenotypic strain changes
      are difficult to identify prior to genome sequencing technology advancement. In
      this chapter, we present the approach using Roche 454 next-generation pyro
      resequencing to identify the genotypic changes such as single nucleotide
      polymorphisms (SNP) associated with an ethanol-tolerant strain of Clostridium
      thermocellum. The parameters used to filter the pyro-resequencing output for SNP
      identification are also discussed. These can help researchers to identify the
      genotypic change of other biocatalysts for strain improvement through metabolic
      engineering.

PMID- 22144358
TI  - Use of proteomic tools in microbial engineering for biofuel production.
AB  - The production of biofuels from renewable sources by microbial engineering has
      gained increased attention due to energy and environmental concerns. Butanol is
      one of the important gasoline-substitute fuels and can be produced by native
      microorganism Clostridium acetobutylicum. To develop a fundamental tool to
      understand C. acetobutylicum, a high resolution proteome reference map for this
      species has been established. To better understand the relationship between
      butanol tolerance and butanol yield, we performed a comparative proteomic
      analysis between the wild-type strain DSM 1731 and its mutant Rh8 at acidogenic
      and solventogenic phases, respectively. The 102 differentially expressed proteins
      that are mainly involved in protein folding, solvent formation, amino acid
      metabolism, protein synthesis, nucleotide metabolism, transport, and others were
      detected. Hierarchical clustering analysis revealed that over 70% of the 102
      differentially expressed proteins in mutant Rh8 were either upregulated (e.g.,
      chaperones and solvent formation related) or downregulated (e.g., amino acid
      metabolism and protein synthesis related) in both acidogenic and solventogenic
      phase, which, respectively, are only upregulated or downregulated in
      solventogenic phase in the wild-type strain.

PMID- 22144359
TI  - Metabolic engineering of antibiotic-producing actinomycetes using in vitro
      transposon mutagenesis.
AB  - A program of mutation and screening, with stepwise reverse engineering or
      "decoding" of the improved strain, is a way to better understand the genetics and
      physiology of the strain improvement process. As more is learned about the
      genetics of strain improvement, it is hoped that more fundamental principles will
      emerge about the types of mutations and genetic manipulations that reliably lead
      to higher producing strains. This will accelerate the construction of higher
      producing strains by metabolic engineering in the future. In this chapter, a
      detailed tagged mutagenesis approach is described using in vitro transposon
      mutagenesis which allowed the successful identification of key genes involved in
      macrolide (erythromycin) antibiotic biosynthesis.

PMID- 22144360
TI  - Use FACS sorting in metabolic engineering of Escherichia coli for increased
      peptide production.
AB  - Many proteins and peptides have been used in therapeutic or industrial
      applications. They are often produced as recombinant forms by microbial
      fermentation. Targeted metabolic engineering of the production strains has
      usually been the approach taken to increase protein production, and this approach
      requires sufficient knowledge about cell metabolism and regulation. Random
      screening is an alternative approach that could circumvent the knowledge
      requirement, but is hampered by lack of suitable high-throughput screening
      methods. We developed a novel fluorescence-activated cell sorting (FACS) method
      to screen for cells with increased peptide production. Using a model peptide rich
      in certain amino acids, we showed that increased fluorescence clones sorted from
      a plasmid expression library contained genes encoding rate-limiting enzymes for
      amino acid synthesis. These expression clones showed increased peptide
      production. This demonstrated that FACS could be used as a very powerful tool for
      metabolic engineering. It can be generally applied to other products or processes
      if the desired phenotype could be correlated with a fluorescence or light
      scattering parameter on the FACS.

PMID- 22144361
TI  - Using flux balance analysis to guide microbial metabolic engineering.
AB  - Metabolic engineers modify biological systems through the use of modern molecular
      biology tools in order to obtain desired phenotypes. However, due to the extreme
      complexity and interconnectedness of metabolism in all organisms, it is often
      difficult to a priori predict which changes will yield the optimal results. Flux
      balance analysis (FBA) is a mathematical approach that uses a genomic-scale
      metabolic network models to afford in silico prediction and optimization of
      metabolic changes. In particular, a genome-scale approach can help select gene
      targets for knockout and overexpression. This approach can be used to help
      expedite the strain engineering process. Here, we give an introduction to the use
      of FBA and provide details for its implementation in a microbial metabolic
      engineering context.

PMID- 22144362
TI  - Using an advanced microfermentor system for strain screening and fermentation
      optimization.
AB  - Industrial biotechnology employs microorganisms (strains) for manufacture of
      certain food or industrial products to meet the increasing need of the world. To
      develop a bioproduction process, the first step is to screen out a production
      strain from isolated, mutated, or genetically engineered strain candidates. To
      maximize the bioproduction of a selected strain, bioreaction (fermentation)
      conditions need to be optimized. Fermentation experiments in shake flasks, bench
      scale fermentors, or a combination of both are the conventional methods for both
      strain screening and fermentation optimization. Shake-flask experiments are easy
      to handle and cost-effective compared to experiments in fermentors, but the lower
      controllability makes the shake-flask data less informative for fermentation
      scale-up. Bench-scale fermentor experiments (>0.5 L) are well controlled under
      designed conditions and provide high-quality data, but they are also very time-
      and cost-consuming. The novel microfermentor system (typically <100 mL), or
      mentioned as microbioreactor, mini-fermentor, mini-bioreactor, or miniature
      bioreactor, combines the advantages of both shake-flask's easy handling and bench
      scale fermentor's controllability, thus can achieve comparable results from
      fermentors at much higher efficiency and lower cost. This chapter introduces an
      example of how to use a microfermentor system for strain screening and
      fermentation optimization.

PMID- 22144363
TI  - Rapid strain evaluation using dynamic DO-stat fed-batch fermentation under scale
      down conditions.
AB  - While large amount of strains can be quickly generated via metabolic engineering,
      the speed/efficiency of evaluating each strain becomes the bottleneck in the
      process from strain development to final production. In this chapter, a method is
      introduced to rapidly evaluate strain performance in fed-batch fermentation mode
      by using dynamic dissolved oxygen stat feed back control with no additional
      advanced online measurement. In addition, a scale-down feature is integrated in
      the method to mimic the limitation of oxygen transfer in large-scale vessels, so
      that strains can be evaluated under the conditions close to that in large-scale
      bioreactors. The method has been implemented in several commercial standard
      benchtop scale fermentation systems with different fermentation control software.

PMID- 22144364
TI  - Preparation and evaluation of lignocellulosic biomass hydrolysates for growth by
      ethanologenic yeasts.
AB  - Lignocellulosic biomass is a potential feedstock for bioethanol production.
      Biomass hydrolysates, prepared with a procedure including pretreatment and
      hydrolysis, are considered to be used as fermentation media for microorganisms,
      such as yeast. During the hydrolysate preparation procedure, toxic compounds are
      released or formed which may inhibit the growth of the microorganism and thus the
      product formation. To study the effects of these compounds on fermentation
      performance, the production of various hydrolysates with diverse inhibitory
      effects is of importance. A platform of methods that generates hydrolysates
      through four different ways and tests their inhibitory effects using Bioscreen C
      Analyzer growth tests is described here. The four methods, based on concentrated
      acid, dilute acid, mild alkaline and alkaline/oxidative conditions, were used to
      prepare hydrolysates from six different biomass sources. The resulting 24
      hydrolysates showed great diversity on growth rate in Bioscreen C Analyzer growth
      tests. The approach allows the prediction of a specific hydrolysate's performance
      and helps to select biomass type and hydrolysate preparation method for a
      specific production strain, or vice versa.

PMID- 22144365
TI  - Engineering whole-cell biosensors with no antibiotic markers for monitoring
      aromatic compounds in the environment.
AB  - A cornerstone of Synthetic Biology is the engineering of gene regulatory
      networks. Construction of such biological circuits has been used not only to
      elucidate the dynamics of gene expression but also for designing whole-cell
      biosensors that translate environmental signals into quantifiable outputs. To
      this end, distinct components of given regulatory systems are rationally rewired
      in a way that translates an external stimulus (for instance, the presence of one
      chemical species) into a measurable readout typically fluorescence or
      luminescence. Various biosensors for BTEX (a mixture of benzene, toluene,
      ethylbenzene and xylenes) are based on XylR, the main transcriptional regulator
      of the TOL pathway of Pseudomonas putida mt-2. In the presence of its natural
      effectors (e.g., m-xylene, toluene or 3-methylbenzylalcohol), XylR triggers
      expression of the upper pathway genes by means of the Pu promoter. Available
      biosensors combine the xylR gene and a direct fusion between the cognate Pu
      promoter and the luxCDABE operon, all components stably integrated in the
      chromosome of P. putida. A versatile development of the same biosensing concept
      is described, aimed at increasing the sensitivity of the genetic circuit toward
      XylR inducers. The new platform utilizes mini-transposon vectors tailored for
      engineering an artificial expression cascade that operates as an amplifier of the
      signal/response ratio of the biosensor. This strategy was applied to the
      construction of a strain that carries a transcriptional fusion between the Pu
      promoter and T7 RNA polymerase (which becomes under the control of XylR and its
      effectors), along with a T7 promoter controlling expression of the luxCDABE
      operon. This simple regulatory architecture produced a dramatic increase of
      bioluminescence emission in respect to the strain that carries only the direct
      fusion between the Pu promoter and the luxCDABE reporter.

PMID- 22144367
TI  - Minimization and prevention of phage infections in bioprocesses.
AB  - Phage infections in bacterial bioprocesses constitute one of the most devastating
      threats to the productivity of the biotechnology facilities. There are several
      factors, which can decide if an infection would occur, and if it would turn into
      an outbreak and heavy contamination of the production facility. This issue is
      discussed on the basis of literature survey and experience of Phage Consultants.

PMID- 22144366
TI  - Metabolic engineering for acetate control in large scale fermentation.
AB  - Escherichia coli is the most commonly used microorganism for production of
      recombinant proteins for different applications. Acetate accumulation during
      aerobic growth on glucose has significant negative impact on recombinant protein
      production in Escherichia coli. Various strategies, such as process and genetic
      approaches have been developed to limit acetate formation to increase the
      productivity of recombinant proteins. We developed a strategy to combine
      inactivation of pyruvate oxidase (poxB) and over-expression of acety-CoA
      synthetase (acs) in E. coli K strain for controlling acetate accumulation. A
      recombinant peptide was expressed and produced in the engineered strains with a
      very low acetate -formation in a 10-L fermentation process.

PMID- 22144368
TI  - Effect of protocol parameters on contrast agent washout curve separability in
      breast dynamic contrast enhanced MRI: a simulation study.
AB  - Variability in diagnostic performance of breast dynamic contrast-enhanced MRI has
      highlighted the need for improved standardization. While guidance exists on some
      aspects of the technique, currently, there is no standardized method for
      selecting repetition time and flip angle, which are important determinants of
      image contrast. This study develops a theoretical framework for quantitative
      optimization of temporal aspects of dynamic contrast-enhanced MRI based on area
      under the receiver operating curve. Optimizations in simulation demonstrate the
      potential for increases in area under the receiver operating characteristic curve
      by up to 0.20 and specificity at a sensitivity of 90% by up to 19%, depending on
      the protocol. These results suggest that careful selection of repetition time and
      flip angle can improve diagnostic performance and identify these quantities as
      potentially important parameters for future standardization.

PMID- 22144369
TI  - Electrochemical tuning of luminescent carbon nanodots: from preparation to
      luminescence mechanism.
AB  - The size of C-nanodots can be electrochemically tuned by changing the applied
      potential during their preparation. The higher the applied potential, the smaller
      the resulting C-nanodots. Moreover, the surface oxidation degree of the C
      nanodots can also be electrochemically tuned. The red-shift of emission
      independent of the size provides an insight into the luminescence mechanism of C
      nanodots.

PMID- 22144370
TI  - Optimization of different process variables for the production of an indolizidine
      alkaloid, swainsonine from Metarhizium anisopliae.
AB  - Swainsonine is a polyhydroxylated indolizidine alkaloid having anticancer,
      antimetastatic, antiproliferative and immunomodulatory activities and also
      potential therapeutic applications against AIDS. In the present study, ten
      isolates of M. anisopliae were screened and enzyme assayed for the production of
      swainsonine in different media (Complex oatmeal, Czapekdox media with and without
      lysine (8% w/v) and Sabouraud dextrose broth (SDB)). Among these strains, ARSEF
      1724 (UM8) was found to produce highest amount of swainsonine (1.34 MUg/l) after
      72 h of incubation under shake flask conditions at 180 rpm and 28  degrees C in
      complex oatmeal media. In order to maximize the yield of swainsonine the media
      composition including macro and micronutrients were optimized. The process
      variables including the chemical factors like carbon sources, nitrogen sources of
      both organic and inorganic nature and pH with constant inoculum size (1 * 10(8)
      spores/ml) were screened using classical one-factor-at-a-time (OFAT) approach to
      find their optimum levels. The present study shows that the nutrient requirement
      is specific for each strain of Metarhizium. Oatmeal extract (6%) was found to be
      the best supporting media along with nitrogen source, glucose (2%) as best carbon
      source and pH (~5) as the best for swainsonine production.

PMID- 22144371
TI  - Recent progress in theoretical and computational chemistry.

PMID- 22144373
TI  - Magnetic properties of paddlewheels and trinuclear clusters with exposed metal
      sites.
AB  - Magnetic exchange-coupling constants of tri- and dinuclear transition-metal
      complexes (paddlewheels) have been computed using various ab initio methods. The
      di- and trinuclear complexes under study may serve as secondary building units in
      metal-organic frameworks (MOFs). Multi-reference methods such as the complete
      active-space self-consistent-field method (CASSCF) as well as second-order
      perturbation theory (CASPT2) yield spin ladders from which the magnetic exchange
      coupling constants are obtained. For the dicobalt paddlewheels, inclusion of spin
      orbit coupling is crucial for obtaining a qualitatively correct description of
      the system. Density functional theory (DFT) was applied in the framework of the
      broken-symmetry approach using single- and double-hybrid functionals as well as
      generalized-gradient-approximation (GGA) functionals. The computed magnetic
      exchange-coupling constants are compared with experimental and other theoretical
      data, where available.

PMID- 22144374
TI  - Oxidative addition of the Calpha-Cbeta bond in beta-O-4 linkage of lignin to
      transition metals using a relativistic pseudopotential-based ccCA-ONIOM method.
AB  - A multi-level multi-layer QM/QM method, the relativistic pseudopotential
      correlation-consistent composite approach within an ONIOM framework (rp-ccCA
      ONIOM), was applied to study the oxidative addition of the C(alpha)-C(beta) bond
      in an archetypal arylglycerol beta-aryl ether (beta-O-4 linkage) substructure of
      lignin to Ni, Cu, Pd and Pt transition metal atoms. The chemically active high
      level layer is treated using the relativistic pseudopotential correlation
      consistent composite approach (rp-ccCA), an efficient methodology designed to
      reproduce an accuracy that would be obtained using the more computationally
      demanding CCSD(T)/aug-cc-pCVinfinityZ-PP, albeit at a significantly reduced
      computational cost, while the low-level layer is computed using B3LYP/cc-pVTZ.
      The thermodynamic and kinetic feasibilities of the model reactions are reported
      in terms of enthalpies of reactions at 298 K (DeltaH degrees (298)) and
      activation energies (DeltaH-act). The results obtained from the rp-ccCA:B3LYP
      hybrid method are compared to the corresponding values using CCSD(T) and several
      density functionals including B3LYP, M06, M06 L, B2PLYP, mPWPLYP and B2GP-PLYP.
      The energetics of the oxidative addition of C?C bond in ethane to Ni, Cu, Pd and
      Pt atoms are also reported to demonstrate that the rp-ccCA method effectively
      reproduces the accuracy of the CCSD(T)/aug-cc-pCVinfinityZ method. Our results
      show that in the catalytic activation of the C(alpha)-C(beta) bond of beta-O-4,
      the use of platinum metal catalysts will lead to the most thermodynamically
      favored reaction with the lowest activation barrier.

PMID- 22144375
TI  - Novel covalent bond in proteins: calculations on model systems question the bond
      stability.
AB  - We have investigated the sulfilimine covalent link between methionine (Met) and
      lysine (Lys), recently identified in collagen IV (R. Vanacore, A.-J. L. Ham, M.
      Voehler, C. R. Sanders, T. P. Conrads, T. D. Veenstra, K. B. Sharpless, P. E.
      Dawson, B. G. Hudson, Science 2009, 325, 1230), and have explored its stability
      with respect to both the redox processes and UV radiation by means of advanced
      computational methods. We have concluded that the bond should be present in a
      protonated state, (-NH=S-)(+). The bond is characterized by a relatively high
      standard reduction potential, that is, the bond should not be stable in a typical
      cell environment; if the sulfilimine bond exists (as suggested by the experiment)
      then the bond has to be supported by the protein environment. The sulfilimine
      bond then destabilizes the protein structure with respect to the alternative
      tertiary structure. We discuss conditions under which the bond could be formed as
      well as other possible structural arrangements consistent with the Met-Lys
      stoichiometry; some of the alternative bond motifs are more thermodynamically
      stable than the sulfilimine bond. We suggest that the character of the Met-Lys
      contact could be approached via NEXAFS spectroscopy. Finally, we show that the
      protonation brings photostability to the sulfilimine bond.

PMID- 22144377
TI  - Acute kidney injury related to pregnancy in developing countries: etiology and
      risk factors in an intensive care unit.
AB  - BACKGROUND: The aim of this study was to determine etiologies, risk factors and
      prognosis of pregnancy-related acute kidney injury (AKI) in an intensive care
      unit. METHODS: Patients included in this retrospective study had a gestational
      age exceeding 20 weeks of amenorrhea. We defined and classified AKI according to
      the criteria of the RIFLE classification. Patients were separated into 2 groups:
      group 1 with AKI and group 2 without AKI. RESULTS: Obstetric admission cases
      (n=137) were compiled, including 46 cases of AKI. Comparison of the different
      variables between groups 1 and 2 revealed a statistically significant difference
      regarding home birth (p=0.004), severe hypotension (p=0.007), icterus (p=0.001),
      oligoanuria (p=0.001), hyperuricemia (p=0.01), thrombopenia (p=0.001) and hepatic
      cytolysis (p=0.001). The incidences of HELLP syndrome, abruptio placentae and
      disseminated intravascular coagulation were higher in the AKI group. Maternal
      mortality was 28.3% in group 1. CONCLUSION: The incidence of AKI in developing
      countries ranges from 4% to 36% depending on the study. In India and Pakistan,
      cases of pregnancy-related AKI occur mainly during the first trimester of
      pregnancy and are related to severe states of sepsis. In Morocco, AKI occurs
      mainly in the third trimester in a context of hypertensive disorders. Maternal
      mortality varies between 6% and 30% depending on the study. AKI is a frequently
      occurring complication in developing countries. It is reversible as shown by
      total recovery of renal function, but this depends on early and appropriate
      diagnosis and treatment. Nevertheless, the best treatment remains prevention.

PMID- 22144378
TI  - Metastatic adenoid cystic carcinoma of the salivary gland responding to cetuximab
      plus weekly paclitaxel after no response to weekly paclitaxel alone.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) of the salivary gland frequently
      develops lung metastases. In cases in which chemotherapy is indicated, resistance
      is a common phenomenon. New drugs, such as cetuximab, have been chosen to avoid
      this chemoresistance. METHODS AND RESULTS: A 54-year-old man was diagnosed with
      ACC of the right submandibular gland. He underwent a submandibular gland
      resection with adjuvant radiotherapy. Three years later, bilateral lung
      metastases were diagnosed and treated with various chemotherapy schedules,
      including paclitaxel without success. We obtained radiographic response, followed
      by disease stabilization for more than 1 year with the addition of cetuximab to
      paclitaxel administered at low weekly doses (metronomic schedule). CONCLUSION:
      This case demonstrates for the first time a reversion of primary resistance to
      chemotherapy in ACC that is currently considered chemoresistant by use of a
      combination of metronomic chemotherapy with new targeted agents such as
      cetuximab. Metronomic chemotherapy was also well tolerated and achieved long-term
      response.

PMID- 22144379
TI  - Predictive ecology: systems approaches.
AB  - The world is experiencing significant, largely anthropogenically induced,
      environmental change. This will impact on the biological world and we need to be
      able to forecast its effects. In order to produce such forecasts, ecology needs
      to become more predictive--to develop the ability to understand how ecological
      systems will behave in future, changed, conditions. Further development of
      process-based models is required to allow such predictions to be made. Critical
      to the development of such models will be achieving a balance between the brute
      force approach that naively attempts to include everything, and over
      simplification that throws out important heterogeneities at various levels.
      Central to this will be the recognition that individuals are the elementary
      particles of all ecological systems. As such it will be necessary to understand
      the effect of evolution on ecological systems, particularly when exposed to
      environmental change. However, insights from evolutionary biology will help the
      development of models even when data may be sparse. Process-based models are more
      common, and are used for forecasting, in other disciplines, e.g. climatology and
      molecular systems biology. Tools and techniques developed in these endeavours can
      be appropriated into ecological modelling, but it will also be necessary to
      develop the science of ecoinformatics along with approaches specific to
      ecological problems. The impetus for this effort should come from the demand
      coming from society to understand the effects of environmental change on the
      world and what might be performed to mitigate or adapt to them.

PMID- 22144380
TI  - The philosophy of modelling or does the philosophy of biology have any use?
AB  - Biologists in search of answers to real-world issues such as the ecological
      consequences of global warming, the design of species' conservation plans,
      understanding landscape dynamics and understanding gene expression make decisions
      constantly that are based on a 'philosophical' stance as to how to create and
      test explanations of an observed phenomenon. For better or for worse, some kind
      of philosophy is an integral part of the doing of biology. Given this, it is more
      important than ever to undertake a practical assessment of what philosophy does
      mean and should mean to biologists. Here, I address three questions: should
      biologists pay any attention to 'philosophy'; should biologists pay any attention
      to 'philosophy of biology'; and should biologists pay any attention to the
      philosophy of biology literature on modelling? I describe why the last question
      is easily answered affirmatively, with the proviso that the practical benefits to
      be gained by biologists from this literature will be directly proportional to the
      extent to which biologists understand 'philosophy' to be a part of biology, not
      apart from biology.

PMID- 22144381
TI  - Modelling ecological systems in a changing world.
AB  - The world is changing at an unprecedented rate. In such a situation, we need to
      understand the nature of the change and to make predictions about the way in
      which it might affect systems of interest; often we may also wish to understand
      what might be done to mitigate the predicted effects. In ecology, we usually make
      such predictions (or forecasts) by making use of mathematical models that
      describe the system and projecting them into the future, under changed
      conditions. Approaches emphasizing the desirability of simple models with
      analytical tractability and those that use assumed causal relationships derived
      statistically from data currently dominate ecological modelling. Although such
      models are excellent at describing the way in which a system has behaved, they
      are poor at predicting its future state, especially in novel conditions. In order
      to address questions about the impact of environmental change, and to understand
      what, if any, action might be taken to ameliorate it, ecologists need to develop
      the ability to project models into novel, future conditions. This will require
      the development of models based on understanding the processes that result in a
      system behaving the way it does, rather than relying on a description of the
      system, as a whole, remaining valid indefinitely.

PMID- 22144382
TI  - Biodiversity in the context of ecosystem services: the applied need for systems
      approaches.
AB  - Recent evidence strongly suggests that biodiversity loss and ecosystem
      degradation continue. How might a systems approach to ecology help us better
      understand and address these issues? Systems approaches play a very limited role
      in the science that underpins traditional biodiversity conservation, but could
      provide important insights into mechanisms that affect population growth. This
      potential is illustrated using data from a critically endangered bird population.
      Although species-specific insights have practical value, the main applied
      challenge for a systems approach is to help improve our understanding of the role
      of biodiversity in the context of ecosystem services (ES) and the associated
      values and benefits people derive from these services. This has profound
      implications for the way we conceptualize and address ecological problems.
      Instead of focusing directly on biodiversity, the important response variables
      become measures of values and benefits, ES or ecosystem processes. We then need
      to understand the sensitivity of these variables to biodiversity change relative
      to other abiotic or anthropogenic factors, which includes exploring the role of
      variability at different levels of biological organization. These issues are
      discussed using the recent UK National Ecosystems Assessment as a framework.

PMID- 22144383
TI  - Individual variation and population dynamics: lessons from a simple system.
AB  - The mapping of environment, through variation in individuals' life histories, to
      dynamics can be complex and often poorly known. Consequently, it is not clear how
      important it is dynamically. To explore this, I incorporated lessons from an
      empirical system, a soil mite, into an individual-based model. Individuals
      compete for resource and allocate this according to eight 'genetic' rules that
      specify investment in growth or reserves (which influences survival or
      fecundity), size at maturation and reproductive allocation. Density dependence,
      therefore, emerges from competition for food, limiting individual's growth and
      fecundity. We use this model to examine the role that genetic and phenotypically
      plastic variation plays in dynamics, by fixing phenotypes, by allowing phenotypes
      to vary plastically and by creating genetic variation between individuals.
      Variation, and how it arises, influences short- and long-run dynamics in a way
      comparable in magnitude with halving food supply. In particular, by switching
      variation on and off, it is possible to identify a range of processes necessary
      to capture the dynamics of the 'full model'. Exercises like this can help
      identify key processes and parameters, but a concerted effort is needed across
      many different systems to search for shared understanding of both process and
      modelling.

PMID- 22144384
TI  - Positive feedback and alternative stable states in inbreeding, cooperation, sex
      roles and other evolutionary processes.
AB  - A large proportion of studies in systems science focus on processes involving a
      mixture of positive and negative feedbacks, which are also common themes in
      evolutionary ecology. Examples of negative feedback are density dependence
      (population regulation) and frequency-dependent selection (polymorphisms).
      Positive feedback, in turn, plays a role in Fisherian 'runaway' sexual selection,
      the evolution of cooperation, selfing and inbreeding tolerance under purging of
      deleterious alleles, and the evolution of sex differences in parental care. All
      these examples feature self-reinforcing processes where the increase in the value
      of a trait selects for further increases, sometimes via a coevolutionary feedback
      loop with another trait. Positive feedback often leads to alternative stable
      states (evolutionary endpoints), making the interpretation of evolutionary
      predictions challenging. Here, we discuss conceptual issues such as the
      relationship between self-reinforcing selection and disruptive selection. We also
      present an extension of a previous model on parental care, focusing on the
      relationship between the operational sex ratio and sexual selection, and the
      influence of this relationship on the evolution of biparental or uniparental
      care.

PMID- 22144385
TI  - Predicting ecosystem dynamics at regional scales: an evaluation of a terrestrial
      biosphere model for the forests of northeastern North America.
AB  - Terrestrial biosphere models are important tools for diagnosing both the current
      state of the terrestrial carbon cycle and forecasting terrestrial ecosystem
      responses to global change. While there are a number of ongoing assessments of
      the short-term predictive capabilities of terrestrial biosphere models using flux
      tower measurements, to date there have been relatively few assessments of their
      ability to predict longer term, decadal-scale biomass dynamics. Here, we present
      the results of a regional-scale evaluation of the Ecosystem Demography version 2
      (ED2)-structured terrestrial biosphere model, evaluating the model's predictions
      against forest inventory measurements for the northeast USA and Quebec from 1985
      to 1995. Simulations were conducted using a default parametrization, which used
      parameter values from the literature, and a constrained model parametrization,
      which had been developed by constraining the model's predictions against 2 years
      of measurements from a single site, Harvard Forest (42.5 degrees  N, 72.1 degrees
      W). The analysis shows that the constrained model parametrization offered marked
      improvements over the default model formulation, capturing large-scale variation
      in patterns of biomass dynamics despite marked differences in climate forcing,
      land-use history and species-composition across the region. These results imply
      that data-constrained parametrizations of structured biosphere models such as ED2
      can be successfully used for regional-scale ecosystem prediction and forecasting.
      We also assess the model's ability to capture sub-grid scale heterogeneity in the
      dynamics of biomass growth and mortality of different sizes and types of trees,
      and then discuss the implications of these analyses for further reducing the
      remaining biases in the model's predictions.

PMID- 22144386
TI  - Individual-scale inference to anticipate climate-change vulnerability of
      biodiversity.
AB  - Anticipating how biodiversity will respond to climate change is challenged by the
      fact that climate variables affect individuals in competition with others, but
      interest lies at the scale of species and landscapes. By omitting the individual
      scale, models cannot accommodate the processes that determine future
      biodiversity. We demonstrate how individual-scale inference can be applied to the
      problem of anticipating vulnerability of species to climate. The approach places
      climate vulnerability in the context of competition for light and soil moisture.
      Sensitivities to climate and competition interactions aggregated from the
      individual tree scale provide estimates of which species are vulnerable to which
      variables in different habitats. Vulnerability is explored in terms of specific
      demographic responses (growth, fecundity and survival) and in terms of the
      synthetic response (the combination of demographic rates), termed climate
      tracking. These indices quantify risks for individuals in the context of their
      competitive environments. However, by aggregating in specific ways (over
      individuals, years, and other input variables), we provide ways to summarize and
      rank species in terms of their risks from climate change.

PMID- 22144387
TI  - Incorporating uncertainty in predictive species distribution modelling.
AB  - Motivated by the need to solve ecological problems (climate change, habitat
      fragmentation and biological invasions), there has been increasing interest in
      species distribution models (SDMs). Predictions from these models inform
      conservation policy, invasive species management and disease-control measures.
      However, predictions are subject to uncertainty, the degree and source of which
      is often unrecognized. Here, we review the SDM literature in the context of
      uncertainty, focusing on three main classes of SDM: niche-based models,
      demographic models and process-based models. We identify sources of uncertainty
      for each class and discuss how uncertainty can be minimized or included in the
      modelling process to give realistic measures of confidence around predictions.
      Because this has typically not been performed, we conclude that uncertainty in
      SDMs has often been underestimated and a false precision assigned to predictions
      of geographical distribution. We identify areas where development of new
      statistical tools will improve predictions from distribution models, notably the
      development of hierarchical models that link different types of distribution
      model and their attendant uncertainties across spatial scales. Finally, we
      discuss the need to develop more defensible methods for assessing predictive
      performance, quantifying model goodness-of-fit and for assessing the significance
      of model covariates.

PMID- 22144388
TI  - From actors to agents in socio-ecological systems models.
AB  - The ecosystem service concept has emphasized the role of people within socio
      ecological systems (SESs). In this paper, we review and discuss alternative ways
      of representing people, their behaviour and decision-making processes in SES
      models using an agent-based modelling (ABM) approach. We also explore how ABM can
      be empirically grounded using information from social survey. The capacity for
      ABM to be generalized beyond case studies represents a crucial next step in
      modelling SESs, although this comes with considerable intellectual challenges. We
      propose the notion of human functional types, as an analogy of plant functional
      types, to support the expansion (scaling) of ABM to larger areas. The expansion
      of scope also implies the need to represent institutional agents in SES models in
      order to account for alternative governance structures and policy feedbacks.
      Further development in the coupling of human-environment systems would contribute
      considerably to better application and use of the ecosystem service concept.

PMID- 22144389
TI  - Interactions between human behaviour and ecological systems.
AB  - Research on the interactions between human behaviour and ecological systems tends
      to focus on the direct effects of human activities on ecosystems, such as
      biodiversity loss. There is also increasing research effort directed towards
      ecosystem services. However, interventions to control people's use of the
      environment alter the incentives that natural resource users face, and therefore
      their decisions about resource use. The indirect effects of conservation
      interventions on biodiversity, modulated through human decision-making, are
      poorly studied but are likely to be significant and potentially counterintuitive.
      This is particularly so where people are dependent on multiple natural resources
      for their livelihoods, when both poverty and biodiversity loss are acute. An
      inter-disciplinary approach is required to quantify these interactions, with an
      understanding of human decision-making at its core; otherwise, predictions about
      the impacts of conservation policies may be highly misleading.

PMID- 22144390
TI  - Bioinformatics tools in predictive ecology: applications to fisheries.
AB  - There has been a huge effort in the advancement of analytical techniques for
      molecular biological data over the past decade. This has led to many novel
      algorithms that are specialized to deal with data associated with biological
      phenomena, such as gene expression and protein interactions. In contrast,
      ecological data analysis has remained focused to some degree on off-the-shelf
      statistical techniques though this is starting to change with the adoption of
      state-of-the-art methods, where few assumptions can be made about the data and a
      more explorative approach is required, for example, through the use of Bayesian
      networks. In this paper, some novel bioinformatics tools for microarray data are
      discussed along with their 'crossover potential' with an application to fisheries
      data. In particular, a focus is made on the development of models that identify
      functionally equivalent species in different fish communities with the aim of
      predicting functional collapse.

PMID- 22144391
TI  - Understanding chilling responses in Arabidopsis seeds and their contribution to
      life history.
AB  - Winter chilling is of central importance in the phenology of temperate annual and
      perennial plants. Chilling accelerates flowering through the process of
      vernalization and breaks both bud and seed dormancy, permitting the onset of
      growth in the spring. The quantitative effects of chilling in floral promotion in
      winter annual Arabidopsis accessions are well-documented, but very little is
      known about the basic physiology underlying summer annual responses to winter
      chilling, which acts on seeds within the soil seed bank. Here, we analyse the
      response of wild accessions to extended chilling in seeds, and explore the
      interaction between seed-maturation temperature and chilling responses. We show
      that two weeks of chilling induces secondary dormancy, and that this time period
      is not dependent on seed-maturation temperature. In addition, we found that seeds
      for most accessions set under simulated summer conditions in the laboratory are
      unable to overwinter in the soil seed bank, as they germinate without light
      during extended chilling treatments. This shows that these seeds are committed to
      re-establishment in the same growing season. Understanding how winter chilling
      affects the timing of Arabidopsis phenology will enable us to explore the
      genetics behind adaptation to changing climates, and inform rational approaches
      to breeding crops with improved performance under new climate scenarios and
      develop a systems ecology of Arabidopsis.

PMID- 22144392
TI  - Pattern-oriented modelling: a 'multi-scope' for predictive systems ecology.
AB  - Modern ecology recognizes that modelling systems across scales and at multiple
      levels-especially to link population and ecosystem dynamics to individual
      adaptive behaviour-is essential for making the science predictive. 'Pattern
      oriented modelling' (POM) is a strategy for doing just this. POM is the multi
      criteria design, selection and calibration of models of complex systems. POM
      starts with identifying a set of patterns observed at multiple scales and levels
      that characterize a system with respect to the particular problem being modelled;
      a model from which the patterns emerge should contain the right mechanisms to
      address the problem. These patterns are then used to (i) determine what scales,
      entities, variables and processes the model needs, (ii) test and select submodels
      to represent key low-level processes such as adaptive behaviour, and (iii) find
      useful parameter values during calibration. Patterns are already often used in
      these ways, but a mini-review of applications of POM confirms that making the
      selection and use of patterns more explicit and rigorous can facilitate the
      development of models with the right level of complexity to understand ecological
      systems and predict their response to novel conditions.

PMID- 22144393
TI  - Systems approaches in global change and biogeochemistry research.
AB  - Systems approaches have great potential for application in predictive ecology. In
      this paper, we present a range of examples, where systems approaches are being
      developed and applied at a range of scales in the field of global change and
      biogeochemical cycling. Systems approaches range from Bayesian calibration
      techniques at plot scale, through data assimilation methods at regional to
      continental scales, to multi-disciplinary numerical model applications at country
      to global scales. We provide examples from a range of studies and show how these
      approaches are being used to address current topics in global change and
      biogeochemical research, such as the interaction between carbon and nitrogen
      cycles, terrestrial carbon feedbacks to climate change and the attribution of
      observed global changes to various drivers of change. We examine how transferable
      the methods and techniques might be to other areas of ecosystem science and
      ecology.

PMID- 22144394
TI  - Making predictive ecology more relevant to policy makers and practitioners.
AB  - One of the aims of ecology is to aid policy makers and practitioners through the
      development of testable predictions of relevance to society. Here, we argue that
      this capacity can be improved in three ways. Firstly, by thinking more clearly
      about the priority issues using a range of methods including horizon scanning,
      identifying policy gaps, identifying priority questions and using evidence-based
      conservation to identify knowledge gaps. Secondly, by linking ecological models
      with models of other systems, such as economic and social models. Thirdly, by
      considering alternative approaches to generate and model data that use, for
      example, discrete or categorical states to model ecological systems. We
      particularly highlight that models are essential for making predictions. However,
      a key to the limitation in their use is the degree to which ecologists are able
      to communicate results to policy makers in a clear, useful and timely fashion.

PMID- 22144395
TI  - H1N1 outbreak in a Swiss military boot camp--observations and suggestions.
AB  - QUESTIONS UNDER STUDY: The A(H1N1)pdm09 influenza virus is a highly contagious
      pathogen which caused the 2009 influenza pandemic. The virus is known to affect
      mainly younger people and may be a problem in crowded living conditions. The aim
      of the study was to describe a major A(H1N1)pdm09 outbreak in a Swiss military
      boot camp and to develop suggestions for similar future situations. METHODS:
      Retrospective chart analysis of a A(H1N1)pdm09 outbreak between 14 December and
      23 December 2010. Symptoms, signs and lab parameters were documented. RESULTS:
      105 of 750 male recruits were affected by the outbreak. All nasopharyngeal swabs
      of 16 patients with high fever were tested positive. Common clinical symptoms
      included high fever, myalgia and bronchitis with persistent cough and throat
      aches. Fever progression typically occurred in two peaks within three days.
      Median length of stay at the infirmary was 3 days (range: 0.5-9 days).
      CONCLUSION: A(H1N1)pdm09 has become a ubiquitous seasonal virus in the region.
      Complications were uncommon and non life threatening. In the event of new
      influenza outbreaks, hygienic and containment measures must be quickly and
      correctly implemented, in order to avoid an epidemic. This should also be
      considered in non-military settings like school camps or in retirement homes.

PMID- 22144396
TI  - Fetal topographical anatomy of the upper abdominal lymphatics: its specific
      features in comparison with other abdominopelvic regions.
AB  - Using semiserial sections from 19 human fetuses of 8-30 weeks gestation, we
      examined the topohistology of the upper abdominal lymphatics and compared it with
      that of the lower abdominal and pelvic lymphatics. The upper abdominal lymphatics
      were characterized by an intimate relationship with the peritoneal lining, a
      common mesentery for the celiac trunk and superior mesenteric artery (SMA).
      Lymphatic connections from the upper abdominal viscera to the paraaortic and
      paracaval areas followed two routes: (1) from the intestinal mesentery, along the
      peritoneum on the left aspect of the proximal SMA, via the chain of lymph
      follicles (LFs) lying along the retropancreatic fusion fascia, to drain into the
      LFs around the left renal vein; (2) from sites along the peritoneum on the
      posterior wall of the omental bursa, via the root of the hepatoduodenal ligament,
      to drain into LFs around the vena cava. The development of these two posterior
      drainage routes seemed to be promoted by the peritoneum or a peritoneal remnant
      (i.e., fusion fascia) attaching to the great vessels, and inhibited or impeded by
      the developing nerves and diaphragm. No paraaortic, paracaval, or pelvic LFs lay
      along the peritoneum. The pelvic LFs were usually located along the bundle of
      lymphatic vessels originating from the femoral canal.

PMID- 22144397
TI  - RF pulse optimization for Bloch-Siegert B 1+ mapping.
AB  - The Bloch-Siegert (B-S) method of B 1+ mapping has been shown to be fast and
      accurate, yet has high SAR and moderately long TE. These limitations can lengthen
      scan times and incur signal loss due to B(0) inhomogeneity, particularly at high
      field. The B-S method relies on applying a band-limited off-resonant B-S
      radiofrequency pulse to induce a B 1+-dependent frequency-shift for resonant
      spins. A method for optimizing the B-S radiofrequency pulse is presented here,
      which maximizes B-S B 1+ measurement sensitivity for a given SAR and T(2) . A 4
      ms optimized pulse is shown to have 35% less SAR compared with the conventional 6
      ms Fermi pulse while still improving B 1+ map angle-to-noise ratio by 22%. The
      optimized pulse performance is validated both in phantom and in vivo brain
      imaging at 7 T.

PMID- 22144398
TI  - Gamma-glutamyltransferase, cardiovascular disease and mortality in individuals
      with diabetes mellitus.
AB  - BACKGROUND: Increased plasma activity of gamma-glutamyltransferase (GGT) is
      associated with cardiovascular diseases (CVD) and mortality in the general
      population. We investigated the association between GGT, CVD and mortality in
      individuals with diabetes mellitus. METHODS: Data used were from 1280
      participants, aged 35-70 years, with a confirmed diagnosis of diabetes mellitus
      in the European Prospective Investigation into Cancer and Nutrition in Potsdam
      (Germany), Bilthoven and Utrecht (the Netherlands). Multivariate hazard ratios
      (HR) and 95% confidence intervals (CI) for CVD (non-fatal and fatal events) and
      overall mortality were estimated using sex-specific quartiles of GGT. RESULTS:
      After 8.2 years follow-up, 108 incident CVD cases and 84 deaths were observed.
      Participants with high GGT activity had an increased mortality risk: HR in the
      highest quartile was 3.96 (95% CI 1.74, 9.00). This association was in particular
      present in former and current smokers, younger persons and those with a higher
      waist-height ratio and alcohol consumption. No associations were observed for non
      fatal CVD and non-fatal and fatal CVD events combined. CONCLUSIONS: Higher GGT
      plasma activity is associated with increased all-cause mortality in individuals
      with diabetes.

PMID- 22144399
TI  - A gold nanocrystal/poly(dimethylsiloxane) composite for plasmonic heating on
      microfluidic chips.

PMID- 22144400
TI  - Enrichment of circulating interleukin-17-secreting interleukin-23 receptor
      positive gamma/delta T cells in patients with active ankylosing spondylitis.
AB  - OBJECTIVE: Ankylosing spondylitis (AS) is a common inflammatory arthritis
      affecting primarily the axial skeleton. IL23R is genetically associated with AS.
      This study was undertaken to investigate and characterize the role of interleukin
      23 (IL-23) signaling in AS pathogenesis. METHODS: The study population consisted
      of patients with active AS (n = 17), patients with psoriatic arthritis (n = 8),
      patients with rheumatoid arthritis, (n = 9), and healthy subjects (n = 20). IL-23
      receptor (IL-23R) expression in T cells was determined in each subject group, and
      expression levels were compared. RESULTS: The proportion of IL-23R-expressing T
      cells in the periphery was 2-fold higher in AS patients than in healthy controls,
      specifically driven by a 3-fold increase in IL-23R-positive gamma/delta T cells
      in AS patients. The proportions of CD4+ and CD8+ cells that were positive for IL
      17 were unchanged. This increased IL-23R expression on gamma/delta T cells was
      also associated with enhanced IL-17 secretion, with no observable IL-17
      production from IL-23R-negative gamma/delta T cells in AS patients. Furthermore,
      gamma/delta T cells from AS patients were heavily skewed toward IL-17 production
      in response to stimulation with IL-23 and/or anti-CD3/CD28. CONCLUSION: Recently,
      mouse models have shown IL-17-secreting gamma/delta T cells to be pathogenic in
      infection and autoimmunity. Our data provide the first description of a
      potentially pathogenic role of these cells in a human autoimmune disease. Since
      IL-23 is a maturation and growth factor for IL-17-producing cells, increased IL
      23R expression may regulate the function of this putative pathogenic gamma/delta
      T cell population.

PMID- 22144403
TI  - Split liver transplantation using extended right grafts: the natural history of
      segment 4 and its impact on early postoperative outcomes.
AB  - Split liver transplantation (SLT) using extended right grafts is associated with
      complications related to ischemia of hepatic segment 4 (S4), and these
      complications are associated with poor outcomes. We retrospectively analyzed 36
      SLT recipients so that we could assess the association of radiological,
      biological, and clinical features with S4 ischemia. The overall survival rates
      were 84.2%, 84.2%, and 77.7% at 1, 3, and 5 years, respectively. The recipients
      were mostly male (24/36 or 67%) and had a median age of 52 years (range = 13-63
      years), a median body mass index of 22.9 kg/m(2) (range = 17.3-29.8 kg/m(2) ),
      and a median graft-to-recipient weight ratio of 1.3% (range = 0.9%-1.9%). S4
      related complications were diagnosed in 22% of the patients (8/36) with a median
      delay of 22 days (range = 10-30 days). Secondary arterial complications were seen
      in 3 of these patients and led to significantly decreased graft survival in
      comparison with the graft survival of patients without complications (50.0%
      versus 85.6%, P = 0.017). Patients developing S4-related complications had
      significantly elevated aspartate aminotransferase (AST) levels (>1000 IU/L) on
      postoperative day (POD) 1 and elevated gamma-glutamyl transpeptidase (GGT) levels
      (>300 IU/L) on PODs 7 and 10 (P < 0.05). These AST and GGT elevations conferred a
      significantly high risk of developing these complications (odds ratio = 42, 95%
      confidence interval = 4-475, P < 0.05). The ischemic volume of S4 was extremely
      variable (0%-95%) and did not correlate with S4-related complications. In
      conclusion, our results suggest that S4-related complications are risk factors
      for worse graft survival, and the development of these complications can be
      anticipated by the early identification of a specific biological profile and a
      routine radiological examination.

PMID- 22144404
TI  - The merger of electrochemistry and molecular electronics.
AB  - Molecular Electronics has the potential to greatly enhance existing silicon-based
      microelectronics to realize new functions, higher device density, lower power
      consumption, and lower cost. Although the investigation of electron transport
      through single molecules and molecular monolayers in "molecular junctions" is a
      recent development, many of the relevant concepts and phenomena are derived from
      electrochemistry, as practiced for the past several decades. The past 10+ years
      have seen an explosion of research activity directed toward how the structure of
      molecules affects electron transport in molecular junctions, with the ultimate
      objective of "rational design" of molecular components with new electronic
      functions, such as chemical sensing, interactions with light, and low-cost, low
      power consumer electronics. In order to achieve these scientifically and
      commercially important objectives, the factors controlling charge transport in
      molecules "connected" to conducting contacts must be understood, and methods for
      massively parallel manufacturing of molecular circuits must be developed. This
      Personal Account describes the development of reproducible and robust molecular
      electronic devices, starting with modified electrodes used in electrochemistry
      and progressing to manufacturable molecular junctions. Although the field faced
      some early difficulties in reliability and characterization, the pieces are now
      in place for rapid advances in understanding charge transport at the molecular
      level. Inherent in the field of Molecular Electronics are many electrochemical
      concepts, including tunneling, redox exchange, activated electron transfer, and
      electron coupling between molecules and conducting contacts.

PMID- 22144401
TI  - Improvement of cellularity on cell block preparations using the so-called tissue
      coagulum clot method during endobronchial ultrasound-guided transbronchial fine
      needle aspiration.
AB  - BACKGROUND: Cell block (CB) preparation during the endobronchial ultrasound
      guided transbronchial fine-needle aspiration (EBUS-TBNA) procedure plays an
      important role in the diagnosis of lung cancer and recovery of cellular material
      for molecular characterization of the tumor. However, the efficiency of the
      conventional method of CB preparation is suboptimal. METHODS: In the current
      study, the "tissue coagulum clot" cell block (TCC-CB) method was used to prepare
      the CBs and its efficiency was compared with that of the conventional saline
      rinse cell block (NR-CB) method. A total of 84 consecutive TCC-CBs (106 lymph
      nodes [LNs] and 14 lung lesions) and 28 consecutive cases of NR-CB (39 LNs and 3
      lung lesions) obtained within the same time period were included in the current
      study. RESULTS: In the TCC-CB specimens, 94 of 106 LN cases (88.7%) yielded
      sufficient diagnostic material, as did 11 of 14 lung lesions (78.6%). In the NR
      CB group, which was used as the control, 22 of 39 LN specimens (56.4%) and none
      of 3 lung specimens (0%) were found to provide sufficient diagnostic material.
      Although the average size of the LNs in the study group were not significantly
      different from those in the control group (1.76 cm vs 1.82 cm; P > .05), the
      overall nondiagnostic rates in the TCC-CB and NR-CB groups were 11.2% and 43.6%,
      respectively (P < .001). The nondiagnostic rates of the lung specimens were 15.4%
      in the TCC-CB group and 100% in the NR-CB group (P < .05). In addition,
      immunohistochemistry studies and epidermal growth factor receptor (EGFR)/KRAS
      mutational analyses were performed in 26 and 14 TCC-CB cases, respectively. With
      the exception of 1 case, all of them had satisfactory results. CONCLUSIONS: The
      data from the current study demonstrate that the TCC-CB method significantly
      increases the cellular yield of CB preparations without compromising
      cytomorphological characterization of tumor cells.

PMID- 22144406
TI  - The Raetz pathway for lipid A biosynthesis: Christian Rudolf Hubert Raetz, M.D.,
      PH.D. 1946-2011.

PMID- 22144408
TI  - Funny turn.

PMID- 22144409
TI  - Data rising from the East.

PMID- 22144410
TI  - Anatomy of the female pelvis.

PMID- 22144411
TI  - HIV epidemic in Europe is not under control, WHO says.

PMID- 22144412
TI  - Australians must have their children fully immunised to receive benefit.

PMID- 22144413
TI  - Government's fund is improving access to drugs for patients with cancer.

PMID- 22144414
TI  - Mid Staffordshire inquiry will advise on dangers of reform and how to avoid them.

PMID- 22144415
TI  - Mass transport to micro- and nanoelectrodes and their arrays: a review.
AB  - The use of micro- and nanoelectrodes and their arrays has become commonplace in
      modern electrochemistry. Numerical simulation is often required for detailed
      analysis of voltammetric data and this relies upon an understanding of the
      prevailing mass transport operating under the experimental conditions. The
      theoretical basis of our understanding of mass transport, particularly diffusion
      and migration, has developed greatly in recent years. We review both theoretical
      and experimental studies which have probed the mass transport at micro- and
      nanoelectrodes and their arrays.

PMID- 22144416
TI  - International Participatory Research Framework: triangulating procedures to build
      health research capacity in Brazil.
AB  - This study advances Community-based Participatory Research (CBPR) by presenting a
      set of triangulated procedures (steps and actions) that can facilitate
      participatory research in myriad international settings. By using procedural
      triangulation-the combination of specific steps and actions as the basis for the
      International Participatory Research Framework (IPRF)-our approach can improve
      the abilities of researchers and practitioners worldwide to systematize the
      development of research partnerships. The IPRF comprises four recursive steps:
      (i) contextualizing the host country; (ii) identifying collaborators in the host
      country; (iii) seeking advice and endorsement from gatekeepers and (iv) matching
      partners' expertise, needs and interests. IPRF includes the following sets of
      recursive participatory actions: (A(1)) becoming familiar with local languages
      and culture; (A(2)) sharing power, ideas, influence and resources; (A(3))
      gathering oral and written information about partners; (A(4)) establishing
      realistic expectations and (A(5)) resolving personal and professional
      differences. We show how these steps and actions were used recursively to build a
      partnership to study the roles of community health workers (CHWs) in Brazil's
      Family Health Program (PSF). The research conducted using IPRF focused on HIV
      prevention, and it included nearly 200 CHWs. By using the IPRF, our partnership
      achieved several participatory outcomes: community-defined research aims,
      capacity for future research and creation of new policies and programs. We
      engaged CHWs who requested that we study their training needs, and we engaged
      CHWs' supervisors who used the data collected to modify CHW training. Data
      collected from CHWs will form the basis for a grant to test CHW training
      curricula. Researchers and community partners can now use the IPRF to build
      partnerships in different international contexts. By triangulating steps and
      actions, the IPRF advances knowledge about the use of CBPR methods/procedures for
      international health research.

PMID- 22144417
TI  - List of essential services under US health reforms is "skimpy" and dangerous, say
      doctors.

PMID- 22144418
TI  - Remote measurement of the leak around the uncuffed tracheal tube: objective
      measurement and physical characteristics.
AB  - BACKGROUND: We have developed a technique for measuring a characteristic of the
      tracheal tube (TT)-trachea interface: the leak conductance (LC). This study aimed
      to validate the technique in the laboratory and to compare LC with measurements
      of fractional volume loss (FVL) in neonates undergoing mechanical ventilation.
      METHODS: LC, expressed as leak flow at a lung pressure of 10 cm H(2)O, was
      derived remotely from ventilator pressure and flow signals. Validation was by
      simulating breathing circuits for 10 models in which LC was measured directly. LC
      was compared with FVL for different settings of PEEP, inspired pressure, and time
      at plateau pressure. Clinically, LC was measured for 135 infants admitted to
      paediatric intensive care after cardiac surgery and compared with FVL. RESULTS:
      No significant differences were found between direct and remote laboratory
      measurements of LC (P>0.05). FVL varied with PEEP, plateau pressure, and time at
      plateau (P<0.05) but LC did not (P>0.05). The between-patient standard deviation
      (sd) of LC (0.4 litre min(-1)) exceeded the within-patient sd of lc (0.05 litre
      min(-1); P<0.05); the between-patient sd of FVL (22.1%) exceeded the within
      patient sd of FVL (1.3%; P<0.05). The median LC was 0.38 (inter-quartile range
      0.29-0.46) litre min(-1). LC was correlated with FVL (r=0.82; 95% confidence
      interval 0.76-0.88) but wide ranges of FVL were observed for patients with
      similar LC. CONCLUSIONS: LC can be derived remotely and was correlated with FVL,
      a conventional proxy for tube fit. It may be a better measure of TT fit than FVL.

PMID- 22144419
TI  - Insulin resistance and endocrine characteristics of the different phenotypes of
      polycystic ovary syndrome: a prospective study.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder
      characterized by oligo- or anovulation (ANOV), biochemical or clinical
      manifestations of hyperandrogenemia (HA) and PCOs. Four phenotypes of PCOS exist
      [phenotype 1 (ANOV + HA + PCO), phenotype 2 (ANOV + HA), phenotype 3 (HA + PCO)
      and phenotype 4 (ANOV + PCO)] but the differences between them are not well
      studied. We compared markers of insulin resistance (IR) and endocrine
      characteristics between the different PCOS phenotypes. METHODS: We prospectively
      studied 1212 consecutive women with PCOS and 254 BMI-matched healthy women.
      RESULTS: Phenotypes 1-4 were present in 48.2, 30.7, 9.7 and 11.4% of patients,
      respectively. BMI did not differ between the four phenotypes and controls. Both
      normal weight and overweight/obese women with phenotypes 1 and 2 were more
      insulin resistant than controls. Overweight/obese, but not normal weight, women
      with phenotype 4 were more insulin resistant than controls, while IR in women
      with phenotype 3 did not differ from controls regardless of obesity. In normal
      weight subjects, women with phenotypes 1 and 2 were more insulin resistant than
      women with phenotype 4. In overweight/obese subjects, women with phenotype 1 were
      more insulin resistant than women with phenotypes 2 and 3 and women with
      phenotype 4 were more insulin resistant than those with phenotype 3. Circulating
      androgens were higher in normal weight and overweight/obese PCOS patients with
      phenotypes 1-3 compared with those with phenotype 4, and higher in normal weight
      PCOS patients with phenotype 1 than in those with phenotype 2. CONCLUSIONS:
      Phenotype 1 is associated with more IR and more pronounced HA than phenotype 2.
      Phenotypes 2 and 4 with obesity, are also characterized by IR. In contrast,
      phenotype 3 is not associated with IR.

PMID- 22144420
TI  - Complications and outcome of assisted reproduction technologies in overweight and
      obese women.
AB  - BACKGROUND: Based on a presumed negative impact of overweight and obesity on
      reproductive capacity and pregnancy outcome, some national guidelines and
      clinicians have argued that there should be an upper limit for a woman's BMI to
      access assisted reproductive technologies (ART). However, evidence on the risk of
      complications or expected success rate of ART in obese women is scarce. We
      therefore performed a systematic review on the subject. METHODS: We searched the
      literature for studies reporting on complications or success rates in overweight
      and obese women undergoing ART. Articles were scored on methodological quality.
      We calculated pooled odds ratios (ORs) to express the association between
      overweight and obesity on the one hand, and complications and success rates of
      ART on the other hand. We only pooled results if data were available per woman
      instead of per cycle or embryo transfer. RESULTS: We detected 14 studies that
      reported on the association between overweight and complications during or after
      ART, of which 6 reported on ovarian hyperstimulation syndrome (OHSS), 7 on
      multiple pregnancies and 6 on ectopic pregnancies. None of the individual studies
      found a positive association between overweight and ART complications. The pooled
      ORs for overweight versus normal weight for OHSS, multiple pregnancy and ectopic
      pregnancy were 1.0 [95% confidence interval (CI) 0.77-1.3], 0.97 (95% CI 0.91
      1.04) and 0.96 (95% CI 0.54-1.7), respectively. In 27 studies that reported on
      BMI and the success of ART, the pooled ORs for overweight versus normal weight on
      live birth, ongoing and clinical pregnancy following ART were OR 0.90 (95% CI
      0.82-1.0), 1.01 (95% CI 0.75-1.4) and OR 0.94 (95% CI 0.69-1.3), respectively.
      CONCLUSIONS: Data on complications following ART are scarce and therefore a
      registration system should be implemented in order to gain more insight into this
      subject. In the available literature, there is no evidence of overweight or
      obesity increasing the risk of complications following ART. Furthermore, they
      only marginally reduce the success rates. Based on the currently available data,
      overweight and obesity in itself should not be a reason to withhold ART.

PMID- 22144421
TI  - Acceptable variability in external quality assessment programmes for basic semen
      analysis.
AB  - BACKGROUND: External quality assessment is essential in modern andrology
      laboratories. To assess the proficiency of laboratories participating in an
      external quality assessment programme (EQAP), limits for acceptable variability
      must be determined. Limits currently specified largely depend on criteria set by
      the organizers of individual EQAP schemes. The objective of this study was to
      evaluate the different criteria described in ISO 13528: 2005 for calculating
      acceptable variability in EQAP when applied to basic semen analysis parameters.
      METHODS AND RESULTS: The data used in this study were the means and standard
      deviations obtained for independent samples from two EQAPs, one national
      (Spanish) and one international (European). The acceptable variability according
      to ISO 13528: 2005 was calculated using four types of criteria: (i) +/- 3
      standard deviations of the results of all participating laboratories; (ii) +/- 3
      standard deviations of the results of expert laboratories; (iii) quality
      specifications based on biological variability, state-of-the-art and clinicians'
      opinions and (iv) the same quality specifications adjusted for the uncertainty of
      the assigned value. The first two strategies resulted in very wide ranges of
      acceptable variability. Conversely, the strategy based only on quality
      specifications resulted in very narrow ranges. For the fourth strategy,
      acceptable ranges were intermediate between the results produced with the other
      strategies. The third and fourth strategies did not produce observable
      differences in acceptable ranges when the model used for calculating the
      specifications of analytical quality was changed. CONCLUSIONS: It is essential
      that EQAPs for semen parameters should determine the ranges for acceptable
      variability in results. Moreover, these ranges must be clinically useful, i.e.
      the variability should have a minimal negative impact on clinical decisions. The
      exact definition of 'expert laboratory' is more important than the model chosen
      for estimating analytical quality specifications in an EQAP for semen parameters
      in basic semen analysis.

PMID- 22144422
TI  - Cancer risks for the relatives of colorectal cancer cases with a methylated MLH1
      promoter region: data from the Colorectal Cancer Family Registry.
AB  - Methylation of the MLH1 gene promoter region is an underlying cause of colorectal
      cancer (CRC) with high microsatellite instability (MSI-H) diagnosed in persons
      without a germ line mutation in a mismatch repair (MMR) gene (non-Lynch Syndrome
      CRC). It is unclear whether relatives of CRC cases with MLH1 methylation have an
      increased risk of colorectal or other cancers. In this retrospective cohort
      study, we assessed risk of CRC and other cancers for the first- and second-degree
      relatives of CRC cases with a methylated MLH1 gene, by comparing observed numbers
      of cases with those expected on the basis of age-, sex-, and country-specific
      cancer incidences (standardized incidence ratios). The cohort consisted of 3,128
      first- and second-degree relatives of the 233 MLH1-methylated CRC cases with no
      MMR or MUTYH gene mutations. The standardized incidence ratio (SIR) for CRC was
      1.60 [95% confidence interval (CI), 1.22-2.16] for first-degree relatives and
      1.08 (0.74-1.60) for second-degree relatives. The SIR for gastric cancer was 2.58
      (1.52-4.71) for first-degree relatives and 4.52 (2.23-10.61) for second-degree
      relatives and, for ovarian cancer, it was 2.16 (1.29-3.86) for first-degree
      relatives. The risk of liver cancer was also increased significantly in first
      degree relatives but the estimate was on the basis of only two cases. These data
      imply that relatives of CRC cases with MLH1 methylation may be at increased risk
      of CRC and stomach cancer and possibly ovarian and liver cancer, suggesting that
      there may be a heritable factor for CRC and other cancers associated with MLH1
      methylation in non-Lynch syndrome CRCs.

PMID- 22144424
TI  - Controversies in mammography screening: let us not ignore science in this never
      ending debate.

PMID- 22144423
TI  - ALDH1A1 is a novel EZH2 target gene in epithelial ovarian cancer identified by
      genome-wide approaches.
AB  - Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in
      the United States. EZH2 silences gene expression through trimethylating lysine 27
      on histone H3 (H3K27Me3). EZH2 is often overexpressed in EOC and has been
      suggested as a target for EOC intervention. However, EZH2 target genes in EOC
      remain poorly understood. Here, we mapped the genomic loci occupied by
      EZH2/H3K27Me3 using chromatin immunoprecipitation followed by next-generation
      sequencing (ChIP-seq) and globally profiled gene expression in EZH2-knockdown EOC
      cells. Cross-examination of gene expression and ChIP-seq revealed a list of 60
      EZH2 direct target genes whose expression was upregulated more than 1.5-fold upon
      EZH2 knockdown. For three selected genes (ALDH1A1, SSTR1, and DACT3), we
      validated their upregulation upon EZH2 knockdown and confirmed the binding of
      EZH2/H3K27Me3 to their genomic loci. Furthermore, the presence of H3K27Me3 at the
      genomic loci of these EZH2 target genes was dependent upon EZH2. Interestingly,
      expression of ALDH1A1, a putative marker for EOC stem cells, was significantly
      downregulated in high-grade serous EOC (n = 53) compared with ovarian surface
      epithelial cells (n = 10, P < 0.001). Notably, expression of ALDH1A1 negatively
      correlated with expression of EZH2 (n = 63, Spearman r = -0.41, P < 0.001). Thus,
      we identified a list of 60 EZH2 target genes and established that ALDH1A1 is a
      novel EZH2 target gene in EOC cells. Our results suggest a role for EZH2 in
      regulating EOC stem cell equilibrium via regulation of ALDH1A1 expression.

PMID- 22144425
TI  - 3D isotropic turbo spin-echo intermediate-weighted sequence with refocusing
      control in knee imaging: comparison study with 3D isotropic fast-field echo
      sequence.
AB  - BACKGROUND: Three-dimensional (3D) turbo spin-echo (TSE) images have been used in
      imaging of the extremities and comparable diagnostic performance to two
      dimensional (2D) TSE images has been reported in several studies. However,
      comparison of the 3D isotropic TSE intermediate-weighted sequence and 3D FFE
      sequence in terms of image quality has not been investigated. PURPOSE: To compare
      the image quality of a 3D isotropic TSE intermediate-weighted sequence with
      refocusing control (volume isotropic turbo spin echo acquisition [VISTA]) and a
      3D isotropic fast-field echo (FFE) sequence of the knee joint. MATERIAL AND
      METHODS: 3.0 T knee MRI with VISTA and 3D FFE sequences was performed in 10
      healthy volunteers (3 men, 7 women; age range 26-30 years). Two radiologists with
      specialties in the musculoskeletal system assessed tissue contrast between the
      fluid-cruciate ligament (F-L), fluid-meniscus (F-M), and fluid-cartilage (F-C)
      based on a 4-point scale (1, poor; 2, fair; 3, good; and 4, excellent).
      Statistical analysis for inter-observer agreement and differences in grades in
      tissue contrast between VISTA and 3D FFE images (Wilcoxon signed-rank) were
      performed. For a quantitative analysis, the signal-to-noise ratio (SNR) was
      obtained by imaging phantom and noise-only image. Image contrast ratios (CRs)
      were calculated between F-L, F-M, and F-C in volunteer images of VISTA and 3D FFE
      and compared statistically with a paired t-test. RESULTS: Based on qualitative
      analysis, VISTA had statistically superior grades of tissue contrast in F-L (P <
      0.001) and F-M (P < 0.001). 3D FFE had superior but not statistically significant
      (P = 0.317) grades in F-C. Based on quantitative analysis, the SNR of the phantom
      imaging was higher in VISTA than that in 3D FFE (28.18 vs. 14.90). VISTA had
      superior CRs in F-L (P < 0.001) and F-M (P < 0.001). 3D FFE had superior CR in F
      C (P = 0.038). CONCLUSION: The VISTA sequence was superior in tissue contrast
      between F-M and F-L, and 3D FFE was superior in tissue contrast between F-C,
      subjectively and quantitatively.

PMID- 22144427
TI  - Dengue maculopathy in a traveler.

PMID- 22144428
TI  - Adaptive trial design: could we use this approach to improve clinical trials in
      the field of global health?
AB  - We need more clinical trials in the world's poorest regions to evaluate new drugs
      and vaccines, and also to find better ways to manage health issues. Clinical
      trials are expensive, time consuming, and cumbersome. However, in wealthier
      regions these limiting factors are being addressed to make trials less
      administrative and improve the designs. A good example is adaptive trial design.
      This innovation is becoming accepted by the regulators and has been taken up by
      the pharmaceutical industry to reduce product development times and costs. If
      this approach makes trials easier and less expensive surely we should be
      implementing this approach in the field of tropical medicine and international
      health? As yet this has rarely been proposed and there are few examples. There is
      a need for raising the awareness of these design approaches because they could be
      used to make dramatic improvements to clinical research in developing countries.

PMID- 22144429
TI  - Nurturing the global workforce in clinical research: the National Institutes of
      Health Fogarty International Clinical Scholars and Fellows Program.
AB  - The Fogarty International Clinical Research Scholars and Fellows Program's goal
      is to foster the next generation of clinical investigators and to help build
      international health research partnerships between American and international
      investigators and institutions. Through June 2012, 61 sites in 27 countries have
      hosted 436 Scholars (American students or junior trainees from the host
      countries) and/or 122 Fellows (American and host country postdoctoral fellows)
      for year-long experiences in global health research. Initially, the program was
      oriented toward infectious diseases, but recently emphasis on chronic disease
      research has increased. At least 521 manuscripts have been published, many in
      high-impact journals. Projects have included clinical trials, observational
      studies, translational research, clinical-laboratory interface initiatives, and
      behavioral research. Strengths of the program include training opportunities for
      American and developing country scientists in well-established international
      clinical research settings, and mentorship from experienced global health
      experts.

PMID- 22144430
TI  - Prevalence of single nucleotide polymorphisms in the Plasmodium falciparum
      multidrug resistance gene (Pfmdr-1) in Korogwe District in Tanzania before and
      after introduction of artemisinin-based combination therapy.
AB  - Tanzania implemented artemether-lumefantrine (AL) as the first-line treatment for
      uncomplicated malaria in November of 2006 because of resistance to sulfadoxine
      pyrimethamine. AL remains highly efficacious, but widespread use may soon
      facilitate emergence of artemisinin tolerance/resistance, which initially may be
      detected at the molecular level as temporal changes in the frequency of single
      nucleotide polymorphisms (SNPs) in the Pfmdr-1 gene associated with AL
      resistance. In Tanzania, 830 Plasmodium falciparum-positive samples collected
      between 2003 and 2010 were examined for SNPs of Pfmdr-1 at codons 86, 184, and
      1246. Both the N86 and 184F increased from 2006 to 2010 (logistic regression;
      N86: odds ratio [95% confidence interval] = 1.35 [1.07-1.71], P = 0.01; 184F:
      odds ratio = 1.42 [1.07-1.88], P = 0.02), and no change was found for D1246 (odds
      ratio = 1.01 [0.80-1.28], P = 0.9). The observed changes may be because of
      introduction of AL, and if so, this finding gives cause for concern and argues
      for continued surveillance of these molecular markers.

PMID- 22144431
TI  - Inhibitory activity of ferroquine, versus chloroquine, against western Kenya
      Plasmodium falciparum field isolates determined by a SYBR Green I in vitro assay.
AB  - Ferroquine (FQ), a chloroquine (CQ) analog, is being developed to treat persons
      with Plasmodium falciparum malaria. In 146 P. falciparum field isolates from
      western Kenya, we measured 50% inhibitory concentrations (IC(50); nM) of CQ and
      FQ by a SYBR Green I in vitro assay. Reference clones included W2 (CQ resistant)
      and D6 (CQ sensitive). Mutation analysis was done for P. falciparum CQ-resistance
      transporter gene (Pfcrt K76T). Median IC(50) values for FQ were lower than CQ for
      field isolates and the W2 clone (both P < 0.05). The Pfcrt mutation (76T), which
      was detected in > 80% of isolates, conferred higher CQ IC(50) values (P < 0.05)
      and modestly lower FQ IC(50) values (P < 0.05), versus Pfcrt wild type (K76). FQ
      is more potent than CQ against CQ-resistant P. falciparum field isolates and the
      W2 clone, and is less affected by Pfcrt 76T. These findings support the notion
      that FQ could be useful in treating persons with P. falciparum malaria.

PMID- 22144432
TI  - Development and evaluation of a rapid diagnostic test for Plasmodium falciparum,
      P. vivax, and mixed-species malaria antigens.
AB  - Plasmodium falciparum and P. vivax malaria are endemic to many parts of the world
      and humans can be co-infected with both species. Because each Plasmodium species
      has different biological and clinical characteristics, accurate differentiation
      of the infecting species is essential for effective treatment. Therefore, we
      produced three monoclonal antibodies that recognize the lactate dehydrogenase of
      P. falciparum, P. vivax, or both to develop the first P. falciparum, P. vivax,
      and mixed-species infections malaria antigen detection kit. The detection limits
      of this kit were 150 and 250 parasites/MUL for P. falciparum and P. vivax,
      respectively, and the kit was able to detect mixed-species infections. The
      sensitivity and specificity of this kit was assessed with 722 clinical specimens.
      Our results showed that its sensitivities for P. falciparum, P. vivax, and mixed
      species infection were 96.5%, 95.3%, and 85.7%, respectively. In addition, its
      specificity was high (99.4%).

PMID- 22144433
TI  - Analysis of polymorphisms in the merozoite surface protein-3alpha gene and two
      microsatellite loci in Sri Lankan Plasmodium vivax: evidence of population
      substructure in Sri Lanka.
AB  - The geographical distribution of genetic variation in Plasmodium vivax samples (N
      = 386) from nine districts across Sri Lanka is described using three markers; the
      P. vivax merozoite surface protein-3alpha (Pvmsp-3alpha) gene, and the two
      microsatellites m1501 and m3502. At Pvmsp-3alpha, 11 alleles were found with an
      expected heterozygosity (H(e)) of 0.81, whereas at m1501 and m3502, 24 alleles
      (H(e) = 0.85) and 8 alleles (H(e) = 0.74) were detected, respectively. Overall,
      95 unique three locus genotypes were detected among the 279 samples positive at
      all three loci (H(e) = 0.95). Calculating the pairwise fixation index (F(ST))
      revealed statistically significant population structure. The presence of
      identical 2-loci microsatellite genotypes in a significant proportion of samples
      revealed local clusters of closely related isolates contributing to strong
      linkage disequilibrium between marker alleles. The results show evidence of high
      genetic diversity and possible population substructure of P. vivax populations in
      Sri Lanka.

PMID- 22144434
TI  - Prevalence of malaria among patients attending public health facilities in Maputo
      City, Mozambique.
AB  - We conducted a health facility-based survey to estimate the prevalence of malaria
      among febrile patients at health facilities (HFs) in Maputo City. Patients
      answered a questionnaire on malaria risk factors and underwent malaria testing. A
      malaria case was defined as a positive result for malaria by microscopy in a
      patient with fever or history of fever in the previous 24 hours. Among 706
      patients with complete information, 111 (15.7%) cases were identified: 105 were
      positive for Plasmodium falciparum only, two for Plasmodium ovale only, and four
      for both P. falciparum and P. ovale. Fever documented at study enrollment, age >=
      5 years, rural HF, and travel outside Maputo City were statistically
      significantly associated with malaria by multivariate analysis. We found a high
      prevalence of laboratory-confirmed malaria among febrile patients in Maputo City.
      Further studies are needed to relate these findings with mosquito density to
      better support malaria prevention and control.

PMID- 22144435
TI  - Case report: Peripheral polyneuropathy and mefloquine prophylaxis.
AB  - We describe a case of a woman who developed a peripheral polyneuropathy shortly
      after completing 4 weekly doses of mefloquine hydrochloride (250 mg) malaria
      prophylaxis. Although mefloquine-related central nervous system neuropathy is
      well described in the literature, peripheral polyneuropathy similar to this case
      has been documented only once before, to our knowledge.

PMID- 22144436
TI  - Review: Improving the therapeutic index of 8-aminoquinolines by the use of drug
      combinations: review of the literature and proposal for future investigations.
AB  - Because 8-aminoquinolines affect critical survival stages of Plasmodium
      parasites, treatment and control of malaria could be markedly improved by more
      widespread use of these drugs; however, hemolytic toxicity, which is widely
      prevalent in G6PD-deficient patients, severely constrains this use. Primaquine
      was approved more than 50 years ago after extensive clinical testing. Review of
      the mid-20th century literature in the light of present understanding of
      pharmacokinetics and metabolism suggests that manipulation of these factors might
      dissociate 8-aminoquinoline efficacy from toxicity and lead to an improved
      therapeutic index.

PMID- 22144439
TI  - Case report: Acute renal injury as a result of liposomal amphotericin B treatment
      in sodium stibogluconate unresponsive visceral leishmaniasis.
AB  - We report an unusual case of visceral leishmaniasis occurring in a patient from
      Sichuan China. The patient presented with a remitting fever, anemia, and
      pancytopenia. The case was confirmed as visceral leishmaniasis by microscopical
      detection of the Leishmania species amastigote in bone marrow aspirate. The
      patient was treated with 10 mg/kg/day of sodium stibogluconate for 5 days, with
      no therapeutic response. As a result, the patient was treated with liposomal
      amphotericin B (LAB) at 10 mg/day as an initial dosage. After treatment with an
      increasing drug dosage for 7 days, acute renal injury was evident as indicated by
      increased serum creatinine and urea nitrogen. LAB administration was discontinued
      until serum creatinine and serum urea nitrogen regressed on Day 15. Two
      maintenance treatments of 100 mg/day LAB were given on Days 19 and 26 (total 870
      mg, 14.5 mg/kg). Bone marrow aspirate and clinical examination suggested total
      remission.

PMID- 22144438
TI  - Characterization of novel Leishmania infantum recombinant proteins encoded by
      genes from five families with distinct capacities for serodiagnosis of canine and
      human visceral leishmaniasis.
AB  - To expand the available panel of recombinant proteins that can be useful for
      identifying Leishmania-infected dogs and for diagnosing human visceral
      leishmaniasis (VL), we selected recombinant antigens from L. infantum, cDNA, and
      genomic libraries by using pools of serum samples from infected dogs and humans.
      The selected DNA fragments encoded homologs of a cytoplasmic heat-shock protein
      70, a kinesin, a polyubiquitin, and two novel hypothetical proteins. Histidine
      tagged recombinant proteins were produced after subcloning these DNA fragments
      and evaluated by using an enzyme-linked immunosorbent assays with panels of
      canine and human serum samples. The enzyme-linked immunosorbent assays with
      different recombinant proteins had different sensitivities (67.4-93.0% and 36.4
      97.2%) and specificities (76.1-100% and 90.4-97.3%) when tested with serum
      samples from Leishmania-infected dogs and human patients with VL. Overall, no
      single recombinant antigen was sufficient to serodiagnosis all canine or human VL
      cases.

PMID- 22144437
TI  - Review: Malaria chemoprophylaxis for travelers to Latin America.
AB  - Because of recent declining malaria transmission in Latin America, some
      authorities have recommended against chemoprophylaxis for most travelers to this
      region. However, the predominant parasite species in Latin America, Plasmodium
      vivax, can form hypnozoites sequestered in the liver, causing malaria relapses.
      Additionally, new evidence shows the potential severity of vivax infections,
      warranting continued consideration of prophylaxis for travel to Latin America.
      Individualized travel risk assessments are recommended and should consider travel
      locations, type, length, and season, as well as probability of itinerary changes.
      Travel recommendations might include no precautions, mosquito avoidance only, or
      mosquito avoidance and chemoprophylaxis. There are a range of good options for
      chemoprophylaxis in Latin America, including atovaquone-proguanil, doxycycline,
      mefloquine, and--in selected areas--chloroquine. Primaquine should be strongly
      considered for nonpregnant, G6PD-nondeficient patients traveling to vivax-endemic
      areas of Latin America, and it has the added benefit of being the only drug to
      protect against malaria relapses.

PMID- 22144440
TI  - Short report: Amebiasis-related mortality among United States residents, 1990
      2007.
AB  - Despite the endemic nature of Entamoeba histolytica infection in the United
      States there is a lack of data on amebiasis-related mortality. We analyzed
      national death certificate data from 1990 to 2007 to assess the occurrence of
      amebiasis-related deaths and determine demographic and regional associations. A
      total of 134 deaths were identified. Mortality rates were highest in males,
      Hispanics, Asian/Pacific Islanders, and persons 75 years of age and older. An
      association with human immunodeficiency virus infection was also observed. A
      declining trend of amebiasis deaths was noted over the 18-year study period. Over
      40% of fatal amebiasis cases occurred in residents of California and Texas.
      United States-born persons accounted for the majority of amebiasis deaths;
      however, all of the fatalities in Asian/Pacific Islanders and 60% of the deaths
      in Hispanics were in foreign-born individuals. Although uncommon, amebiasis
      related deaths routinely occur in the United States.

PMID- 22144441
TI  - Seventeen years of annual distribution of ivermectin has not interrupted
      onchocerciasis transmission in North Region, Cameroon.
AB  - We studied onchocerciasis transmission and impact on ocular morbidity in three
      health districts in North Region, Cameroon, where annual mass ivermectin
      treatment has been provided for 12-17 years. The studies, which took place from
      2008 to 2010, consisted of skin snips for microfilariae (mf), palpation
      examinations for nodules, slit lamp examinations for mf in the eye, and Simulium
      vector dissections for larval infection rates. Adults had mf and nodule rates of
      4.8% and 13.5%, respectively, and 5.5% had mf in the anterior chamber of the eye.
      Strong evidence of ongoing transmission was found in one health district, where
      despite 17 years of annual treatments, the annual transmission potential was 543
      L3/person per year; additionally, children under 10 years of age had a 2.6% mf
      prevalence. Halting ivermectin treatments in North Cameroon now might risk
      recrudescence of transmission and ocular disease.

PMID- 22144442
TI  - Short report: Molecular characterization of Blastocystis obtained from members of
      the indigenous Tapirape ethnic group from the Brazilian Amazon region, Brazil.
AB  - A total of 382 stool samples were examined during a survey of intestinal
      parasites in members of the Tapirape ethnic group, who live in the Brazilian
      Amazon region of Mato Grosso. Fecal DNAs from Blastocystis-positive samples were
      extracted, polymerase chain reaction amplified using Blastocystis-specific
      primers targeting the small subunit rRNA gene, and sequenced. Three subtypes
      (STs) were identified: ST1 (41%), ST2 (32%), and ST3 (17%). Seven mixed
      infections were found (11%). The subtype distribution was markedly different from
      that reported in Europe in that ST4 was not detected and ST3 was not the most
      common subtype. This study is the first to include molecular characterization of
      Blastocystis in Brazil and in indigenous communities from Latin America.

PMID- 22144443
TI  - Evaluation of an IgY-based immunomagnetic enzyme-linked immunosorbent assay
      system for detection of circulating Schistosoma japonicum antigen in serum
      samples from patients in China.
AB  - We have developed a novel egg yolk antibody (IgY)-coated magnetic beads antigen
      capture immunoassay for detection of a circulating antigen of Schistosoma
      japonicum in serum samples of patients in schistosomiasis-endemic areas of China.
      This IgY-based immunomagnetic bead enzyme-linked immunosorbent assay (IgY-IMB
      ELISA) uses polyclonal IgY-coated magnetic beads as a capture antibody, and a
      monoclonal IgG as a detection antibody. The sensitivity of the magnetic
      immunoassay was 100% (40 of 40) in cases of acute infection and 91.5% (107 of
      117) in chronic cases of schistosomiasis, and no positive reaction was found in 0
      of 49 healthy persons. Cross-reactivity was 3.3% (1 of 33) with clonorchiasis and
      0% (0 of 20) with paragonimiasis. There was a significant correlation between
      ELISA absorbance value and egg count (eggs per gram feces) and a correlation
      coefficient of 0.88 in a small sample of 14 patients. The results demonstrated
      that the IgY-IMB-ELISA is a sensitive and specific assay for detection of human
      schistosomiasis japonica.

PMID- 22144444
TI  - HIV target cells in Schistosoma haematobium-infected female genital mucosa.
AB  - The parasite Schistosoma haematobium frequently causes genital lesions in women
      and could increase the risk of human immunodeficiency virus (HIV) transmission.
      This study quantifies the HIV target cells in schistosome-infected female genital
      mucosa. Cervicovaginal biopsies with and without schistosomiasis were
      immunostained for quantification of CD4(+) T lymphocytes (CD3, CD8), macrophages
      (CD68), and dendritic Langerhans cells (S100 protein). We found significantly
      higher densities of genital mucosal CD4(+) T lymphocytes and macrophages
      surrounding schistosome ova compared with cervicovaginal mucosa without ova (P =
      0.034 and P = 0.018, respectively). We found no increased density of Langerhans
      cells (P = 0.25). This study indicates that S. haematobium may significantly
      increase the density of HIV target cells (CD4(+) T lymphocytes and macrophages)
      in the female genitals, creating a beneficial setting for HIV transmission.
      Further studies are needed to confirm these findings and to evaluate the effect
      of anti-schistosomal treatment on female genital schistosomiasis.

PMID- 22144446
TI  - Learning curve of vesico-urinary ultrasonography in Schistosoma haematobium
      infection with WHO practical guide: a "simple to learn" examination.
AB  - In developing countries, it is difficult to rally a radiologist to conduct field
      studies. Here, we report how a radiologist taught a clinician to carry out the
      ultrasound examination as defined by the World Health Organization (WHO) record
      sheet for Schistosoma haematobium related lesions. In a population infected with
      S. haematobium, the learner and teacher performed two ultrasound exams and the
      results were compared. One hundred thirty-two children were prospectively
      included, during 8 ultrasonography sessions split over 23 days. After 51
      examinations the learner's sensitivity was above 90%. After the fifth session the
      specificity reached 100% (results remained stable until the end of the study
      period). This study shows that a clinician can quickly learn how to carry out a
      simple ultrasound examination to gather the items needed for the follow-up of S.
      haematobium related lesions, suggesting that clinicians could implement networks
      of ultrasound-based surveillance on the field.

PMID- 22144445
TI  - Impact of drought on the spatial pattern of transmission of Schistosoma
      haematobium in coastal Kenya.
AB  - We analyzed temporal changes in spatial patterns of active Schistosoma
      haematobium infection in different age groups and associated them with ponds
      infested with Bulinus snails. A major drought between 2001 and 2009 resulted in
      drying of ponds that were known sources of infection, and we detected very few or
      no snails in ponds that were infested in the past. The household-level spatial
      pattern of infection for children of various age groups in 2009 was contrasted
      with historical data from 2000. The significant local clustering of high- and low
      infection levels among school-aged children that occurred in 2000 was absent in
      2009. We attribute the disappearance of significant clustering around historical
      transmission hot spots to a decade-long drought in our study area. The
      implications of extreme weather and climate conditions on risk and transmission
      of S. haematobium and their relevance to control strategies are discussed.

PMID- 22144447
TI  - Long-term albendazole effectiveness for hepatic cystic echinococcosis.
AB  - Little is known about the long-term effectiveness of albendazole in the medical
      therapy of non-complicated hepatic cystic echinococcosis (HCE) in resource
      constrained settings. We performed a retrospective review of patients starting
      albendazole for HCE in Lima, Peru from January 1997 to December 2007. Patients
      successfully recontacted underwent chart abstraction and clinical and
      ultrasonographic reevaluation. Descriptive statistics were used to delineate
      patient characteristics and treatment effectiveness at the conclusion of
      albendazole and after reevaluation. Patients (N = 27) were primarily female, mean
      age was 51. Initial treatment success at albendazole conclusion was 26% (N = 7)
      per patient and 37.5% (N = 24) per cyst. After 3.8 +/- 2.5 years, albendazole
      success was 34% (N = 9) per patient and 40% (N = 24) per cyst. We found a gap in
      the effectiveness of albendazole HCE therapy compared with the efficacy reported
      in clinical trials. This underscores the need for further investigation into
      alternate therapeutic strategies for this neglected disease.

PMID- 22144448
TI  - The combination of indoor residual spraying and insecticide-treated nets provides
      added protection against malaria compared with insecticide-treated nets alone.
AB  - Both insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS)
      reduce malaria in high malaria transmission areas. The combined effect of these
      interventions is unknown. We conducted a non-randomized prospective cohort study
      to determine protective efficacy of IRS with ITNs (ITN + IRS) compared with ITNs
      alone (ITN only) in preventing Plasmodium falciparum parasitemia. At baseline,
      participants provided blood samples for malaria smears, were presumptively
      treated for malaria, and received ITNs. Blood smears were made monthly and at
      sick visits. In total, 1,804 participants were enrolled. Incidence of P.
      falciparum parasitemia in the ITN + IRS and ITN only groups was 18 and 44
      infections per 100 persons-years at risk, respectively (unadjusted rate ratio =
      0.41; 95% confidence interval [CI] = 0.31-0.56). Adjusted protective efficacy of
      ITN + IRS compared with ITN only was 62% (95% CI = 0.50-0.72). The combination of
      IRS and ITN might be a feasible strategy to further reduce malaria transmission
      in areas of persistent perennial malaria transmission.

PMID- 22144449
TI  - Spatial stability of adult Aedes aegypti populations.
AB  - Vector control programs could be more efficient by identifying the location of
      highly productive sites of Aedes aegypti. This study explored if the number of
      female adults of Ae. aegypti in BG-Sentinel traps was clustered and if their
      spatial distribution changed in time in two neighborhoods in San Juan, Puerto
      Rico. Traps were uniformly distributed across each neighborhood (130 m from each
      other), and samples were taken every 3 weeks. Global and local spatial
      autocorrelations were explored. Spatial stability existed if the rank order of
      trap captures was kept in time. There was lack of global autocorrelation in both
      neighborhoods, precluding their stratification for control purposes. Hot and cold
      spots were identified, revealing the highly focal nature of Ae. aegypti. There
      was significant spatial stability throughout the study in both locations. The
      consistency in trap productivity in time could be used to increase the
      effectiveness of vector and dengue control programs.

PMID- 22144450
TI  - Short report: The effect of preservation methods on predicting mosquito age by
      near infrared spectroscopy.
AB  - Determining mosquito age is important to evaluate vector control programs because
      the ability to transmit diseases is age dependent. Current age-grading techniques
      require dissection or RNA extraction. Near infrared spectroscopy has been used to
      rapidly and nondestructively determine the age of fresh mosquitoes and specimens
      stored in RNAlater, but other preservation techniques have not been examined.
      Thus, in this study, we investigate whether age can be predicted from insects
      preserved by various common methods. Results from this study show that age can be
      predicted from mosquitoes preserved with desiccants, ethanol, Carnoy, RNAlater,
      or refrigeration with confidence intervals < 1.4 days. The best results were
      generally obtained from mosquitoes stored using desiccants, RNAlater, or
      refrigeration.

PMID- 22144451
TI  - Short report: Seroprevalence of human leptospirosis in Reunion Island (Indian
      Ocean) assessed by microscopic agglutination test on paper disc-absorbed whole
      blood.
AB  - In the last decade, leptospirosis has emerged as a globally important infectious
      disease. Humans most commonly become infected through occupational, recreational,
      or domestic contact with the urine of carrier animals, either directly or through
      contaminated water or soil. The disease occurs in urban areas of industrialized
      and developing countries as well as rural regions worldwide. We present a
      retrospective study conducted in 2006 on 2,269 randomly selected Reunion Island
      inhabitants. Blood sampling was performed on individual blotting papers, and
      microscopic agglutination test (MAT) was conducted on paper disc-absorbed (PDA)
      blood. We showed that seroprevalence of leptospirosis was 0.66% +/- 0.34 in the
      global population of Reunion Island, which is 1.78 lower than the seroprevalence
      estimated 20 years before. The serological method is described, and the results
      discussion focuses on methodology and socio-economic factors.

PMID- 22144452
TI  - Mycobacterium ulcerans infection (Buruli ulcer) on the face: a comparative
      analysis of 13 clinically suspected cases from the Democratic Republic of Congo.
AB  - We report our experience in managing 13 consecutive clinically suspected cases of
      Buruli ulcer on the face treated at the hospital of the Institut Medical
      Evangelique at Kimpese, Democratic Republic of Congo diagnosed during 2003-2007.
      During specific antibiotherapy, facial edema diminished, thus minimizing the
      subsequent extent of surgery and severe disfigurations. The following
      complications were observed: 1) lagophthalmos from scarring in four patients and
      associated ectropion in three of them; 2) blindness in one eye in one patient; 3)
      disfiguring exposure of teeth and gums resulting from excision of the left labial
      commissure that affected speech, drinking, and eating in one patient; and 4)
      dissemination of Mycobacterium ulcerans infection in three patients. Our study
      highlights the importance of this clinical presentation of Buruli ulcer, and the
      need for health workers in disease-endemic areas to be aware of the special
      challenges management of Buruli ulcer on the face presents.

PMID- 22144453
TI  - Help-seeking for pre-ulcer and ulcer conditions of Mycobacterium ulcerans disease
      (Buruli ulcer) in Ghana.
AB  - This study examined sociocultural features of help-seeking for Buruli ulcer
      affected persons with pre-ulcers and ulcers in a disease-endemic area in Ghana. A
      sample of 181 respondents were purposively selected. Fisher's exact test was used
      to compare help-seeking variables for pre-ulcers and ulcers. Qualitative
      phenomenologic analysis of narratives clarified the meaning and content of
      selected quantitative help-seeking variables. For pre-ulcers, herbal dressings
      were used to expose necrotic tissues and subsequently applied as dressings for
      ulcers. Analgesics and left-over antibiotics were used to ease pain and reduce
      inflammation. Choices for outside-help were influenced by the perceived
      effectiveness of the treatment, the closeness of the provider to residences, and
      family and friends. Health education is required to emphasize the risk of self
      medication with antibiotics and the importance of medical treatment for pre
      ulcers, and to caution against the use of herbs to expose necrotic tissues, which
      could lead to co-infections.

PMID- 22144454
TI  - Elimination of Borrelia burgdorferi and Anaplasma phagocytophilum in rodent
      reservoirs and Ixodes scapularis ticks using a doxycycline hyclate-laden bait.
AB  - A field trial was conducted in a Lyme disease-endemic area of New Jersey to
      determine the efficacy of a doxycyline hyclate rodent bait to prophylactically
      protect and cure small-mammal reservoirs and reduce infection rates in questing
      Ixodes scapularis ticks for Borrelia burgdorferi and Anaplasma phagocytophilum.
      The doxycycline-laden bait was formulated at a concentration of 500 mg/kg and
      delivered during the immature tick feeding season in rodent-targeted bait boxes.
      The percentage of infected small mammals recovered from treated areas after 2
      years of treatment was reduced by 86.9% for B. burgdorferi and 74% for A.
      phagocytophilum. Infection rates in questing nymphal ticks for both B.
      burgdorferi and A. phagocytophilum were reduced by 94.3% and 92%, respectively.
      Results from this study indicate that doxycycline-impregnated bait is an
      effective means of reducing infection rates for B. burgdorferi and A.
      phagocytophilum in both rodent reservoirs and questing I. scapularis ticks.

PMID- 22144455
TI  - Case report: Severe typhus group rickettsiosis complicated by pulmonary edema in
      a returning traveler from Indonesia.
AB  - We report a severe case of typhus group rickettsiosis in a returning traveler
      from Indonesia. This typically mild illness was characterized by progressive
      pulmonary edema and prolonged fever, with defervescence 4 days after the
      commencement of doxycycline.

PMID- 22144456
TI  - Short report: Race and rickettsiae: a United States perspective.
AB  - US surveillance programs for Rocky Mountain spotted fever (RMSF), ehrlichiosis,
      and anaplasmosis collect demographic data on patients, including race and
      ethnicity. Reporting of these diseases among race groups is not uniform across
      the United States. Because a laboratory confirmation is required to meet the
      national surveillance case definition, reporting may be influenced by a patient's
      access to healthcare. Determining the association between race and ethnicity with
      incidence of rickettsial infections requires targeted, active surveillance.

PMID- 22144457
TI  - Examining the use of oral rehydration salts and other oral rehydration therapy
      for childhood diarrhea in Kenya.
AB  - Reductions in the use of oral rehydration therapy (ORT) in sub-Saharan Africa
      highlight the need to examine caregiver perceptions of ORT during diarrheal
      episodes. Qualitative research involving group discussions with childcare
      providers and in-depth interviews with 45 caregivers of children < 5 years of age
      who had experienced diarrhea was conducted in one rural and urban site in Kenya
      during July-December 2007. Diarrhea was considered a dangerous condition that can
      kill young children. Caregivers preferred to treat diarrhea with Western drugs
      believed to be more effective in stopping diarrhea than ORT. Inconsistent
      recommendations from health workers regarding use of oral rehydration solution
      (ORS) caused confusion about when ORS is appropriate and whether it requires a
      medical prescription. In the rural community, causal explanations about diarrhea,
      beliefs in herbal remedies, cost, and distance to health facilities presented
      additional barriers to ORS use. Health communication is needed to clarify the
      function of ORT in preventing dehydration.

PMID- 22144458
TI  - Community case management of childhood diarrhea in a setting with declining use
      of oral rehydration therapy: findings from cross-sectional studies among primary
      household caregivers, Kenya, 2007.
AB  - We sought to determine factors associated with appropriate diarrhea case
      management in Kenya. We conducted a cross-sectional survey of caregivers of
      children < 5 years of age with diarrhea in rural Asembo and urban Kibera. In
      Asembo, 61% of respondents provided oral rehydration therapy (ORT), 45% oral
      rehydration solution (ORS), and 64% continued feeding. In Kibera, 75% provided
      ORT, 43% ORS, and 46% continued feeding. Seeking care at a health facility, risk
      perception regarding death from diarrhea, and treating a child with oral
      medications were associated with ORT and ORS use. Availability of oral medication
      was negatively associated. A minority of caregivers reported that ORS is
      available in nearby shops. In Kenya, household case management of diarrhea
      remains inadequate for a substantial proportion of children. Health workers have
      a critical role in empowering caregivers regarding early treatment with ORT and
      continued feeding. Increasing community ORS availability is essential to
      improving diarrhea management.

PMID- 22144459
TI  - Short report: Molecular insights for Giardia, Cryptosporidium, and soil
      transmitted helminths from a facility-based surveillance system in Guatemala.
AB  - We molecularly characterized samples with Giardia, Cryptosporidium, and soil
      transmitted helminths from a facility-based surveillance system for diarrhea in
      Santa Rosa, Guatemala. The DNA sequence analysis determined the presence of
      Giardia assemblages A (N = 7) and B (N = 12) and, Cryptosporidium hominis (N = 2)
      and Cryptosporidium parvum (N = 2), suggestive of different transmission cycles.
      All 41 samples with soil-transmitted helminths did not have the beta-tubulin
      mutation described for benzimidazole resistance, suggesting potential usefulness
      in mass drug administration campaigns.

PMID- 22144460
TI  - Short report: Rapid-test based identification of influenza as an etiology of
      acute febrile illness in Cambodia.
AB  - Influenza can be manifested as an acute febrile illness, with symptoms similar to
      many pathogens endemic to Cambodia. The objective of this study was to evaluate
      the Quickvue influenza A+B rapid test to identify the etiology of acute febrile
      illness in Cambodia. During December 2006-May 2008, patients enrolled in a study
      to identify the etiology of acute febrile illnesses were tested for influenza by
      real-time reverse transcriptase PCR (RT-PCR) and Quickvue influenza A+B rapid
      test. The prevalence of influenza was 19.7% by RT-PCR. Compared with RT-PCR, the
      sensitivity and specificity of the rapid test were 52.1% and 92.5%, respectively.
      The influenza rapid test identified the etiology in 10.2% of enrollees and >= 35%
      during peak times of influenza activity. This study suggests that rapid influenza
      tests may be useful during peak times of influenza activity in an area where
      several different etiologies can present as an acute febrile illness.

PMID- 22144462
TI  - Voyager measurements of hydrogen Lyman-alpha diffuse emission from the Milky Way.
AB  - Doppler-shifted hydrogen Lyman-alpha (Lyalpha) emission from galaxies is
      currently measured and used in cosmology as an indicator of star formation. Until
      now, the Milky Way emission has not been detected, owing to far brighter local
      sources, including the H (hydrogen) glow, i.e., solar Lyalpha radiation
      backscattered by interstellar atoms that flow within the solar system. Because
      observations from the Voyager spacecraft, now leaving the heliosphere, are
      decreasingly affected by the H glow, the ultraviolet spectrographs are detecting
      Lyalpha diffuse emission from our Galaxy. The surface brightness toward nearby
      star-forming regions is about 3 to 4 rayleighs. The escape fraction of the
      radiation from the brightest H II regions is on the order of 3% and is highly
      spatially variable. These results will help in constraining models of Lyalpha
      radiation transfer in distant galaxies.

PMID- 22144461
TI  - Candidate vectors and rodent hosts of Venezuelan equine encephalitis virus,
      Chiapas, 2006-2007.
AB  - Enzootic Venezuelan equine encephalitis virus (VEEV) has been known to occur in
      Mexico since the 1960s. The first natural equine epizootic was recognized in
      Chiapas in 1993 and since then, numerous studies have characterized the etiologic
      strains, including reverse genetic studies that incriminated a specific mutation
      that enhanced infection of epizootic mosquito vectors. The aim of this study was
      to determine the mosquito and rodent species involved in enzootic maintenance of
      subtype IE VEEV in coastal Chiapas. A longitudinal study was conducted over a
      year to discern which species and habitats could be associated with VEEV
      circulation. Antibody was rarely detected in mammals and virus was not isolated
      from mosquitoes. Additionally, Culex (Melanoconion) taeniopus populations were
      found to be spatially related to high levels of human and bovine seroprevalence.
      These mosquito populations were concentrated in areas that appear to represent
      foci of stable, enzootic VEEV circulation.

PMID- 22144463
TI  - RNA elimination machinery targeting meiotic mRNAs promotes facultative
      heterochromatin formation.
AB  - Facultative heterochromatin that changes during cellular differentiation
      coordinates regulated gene expression, but its assembly is poorly understood.
      Here, we describe facultative heterochromatin islands in fission yeast and show
      that their formation at meiotic genes requires factors that eliminate meiotic
      messenger RNAs (mRNAs) during vegetative growth. Blocking production of meiotic
      mRNA or loss of RNA elimination factors, including Mmi1 and Red1 proteins,
      abolishes heterochromatin islands. RNA elimination machinery is enriched at
      meiotic loci and interacts with Clr4/SUV39h, a methyltransferase involved in
      heterochromatin assembly. Heterochromatin islands disassemble in response to
      nutritional signals that induce sexual differentiation. This process involves the
      antisilencing factor Epe1, the loss of which causes dramatic increase in
      heterochromatic loci. Our analyses uncover unexpected regulatory roles for mRNA
      processing factors that assemble dynamic heterochromatin to modulate gene
      expression.

PMID- 22144464
TI  - Candle soot as a template for a transparent robust superamphiphobic coating.
AB  - Coating is an essential step in adjusting the surface properties of materials.
      Superhydrophobic coatings with contact angles greater than 150 degrees  and roll
      off angles below 10 degrees  for water have been developed, based on low-energy
      surfaces and roughness on the nano- and micrometer scales. However, these
      surfaces are still wetted by organic liquids such as surfactant-based solutions,
      alcohols, or alkanes. Coatings that are simultaneously superhydrophobic and
      superoleophobic are rare. We designed an easily fabricated, transparent, and oil
      rebounding superamphiphobic coating. A porous deposit of candle soot was coated
      with a 25-nanometer-thick silica shell. The black coating became transparent
      after calcination at 600 degrees C. After silanization, the coating was
      superamphiphobic and remained so even after its top layer was damaged by sand
      impingement.

PMID- 22144465
TI  - Isotopic evidence for massive oxidation of organic matter following the great
      oxidation event.
AB  - The stable isotope record of marine carbon indicates that the Proterozoic Eon
      began and ended with extreme fluctuations in the carbon cycle. In both the
      Paleoproterozoic [2500 to 1600 million years ago (Ma)] and Neoproterozoic (1000
      to 542 Ma), extended intervals of anomalously high carbon isotope ratios
      (delta(13)C) indicate high rates of organic matter burial and release of oxygen
      to the atmosphere; in the Neoproterozoic, the high delta(13)C interval was
      punctuated by abrupt swings to low delta(13)C, indicating massive oxidation of
      organic matter. We report a Paleoproterozoic negative delta(13)C excursion that
      is similar in magnitude and apparent duration to the Neoproterozoic anomaly. This
      Shunga-Francevillian anomaly may reflect intense oxidative weathering of rocks as
      the result of the initial establishment of an oxygen-rich atmosphere.

PMID- 22144466
TI  - The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune
      quiescence.
AB  - The blood-brain barrier (BBB) is composed of tightly bound endothelial cells
      (ECs) and perivascular astrocytes that regulate central nervous system (CNS)
      homeostasis. We showed that astrocytes secrete Sonic hedgehog and that BBB ECs
      express Hedgehog (Hh) receptors, which together promote BBB formation and
      integrity during embryonic development and adulthood. Using pharmacological
      inhibition and genetic inactivation of the Hh signaling pathway in ECs, we also
      demonstrated a critical role of the Hh pathway in promoting the immune quiescence
      of BBB ECs by decreasing the expression of proinflammatory mediators and the
      adhesion and migration of leukocytes, in vivo and in vitro. Overall, the Hh
      pathway provides a barrier-promoting effect and an endogenous anti-inflammatory
      balance to CNS-directed immune attacks, as occurs in multiple sclerosis.

PMID- 22144467
TI  - Astronomy. Voyagers of discovery.

PMID- 22144468
TI  - Molecular biomarkers of risk in premalignancy and breast cancer prevention.
AB  - About 50,000 U.S. women are diagnosed with breast atypical hyperplasia each year,
      giving them about a six-fold increased relative risk of developing invasive
      breast cancer (IBC) compared with age-matched controls. Still, only a small
      fraction of patients with atypical hyperplasia ever progress to IBC, which is a
      major reason why a large majority do not participate in breast cancer prevention,
      despite the remarkable effectiveness of currently available risk-reducing
      therapies. An interesting study reported by Radisky and colleagues in this issue
      of the journal (beginning on page 1953) evaluated expression levels of p16(ink4a)
      in atypical hyperplasia for more accurately predicting risk--hoping to identify
      high-risk patients who will benefit most from therapy while sparing those with
      lower risk from unnecessary therapy. Unfortunately, p16(ink4a) expression was not
      prognostic in this particular study, although research to identify powerful
      biomarkers of risk remains a high priority. Fortunately, there are many other
      promising biomarkers under investigation, as well as several underutilized
      experimental strategies which could help promote successful breast cancer
      prevention.

PMID- 22144470
TI  - Monoallelic expression determines oncogenic progression and outcome in benign and
      malignant brain tumors.
AB  - Although monoallelic expression (MAE) is a frequent genomic event in normal
      tissues, its role in tumorigenesis remains unclear. Here we carried out single
      nucleotide polymorphism arrays on DNA and RNA from a large cohort of pediatric
      and adult brain tumor tissues to determine the genome-wide rate of MAE, its role
      in specific cancer-related genes, and the clinical consequences of MAE in brain
      tumors. We also used targeted genotyping to examine the role of tumor-related
      genes in brain tumor development and specifically examined the clinical
      consequences of MAE at TP53 and IDH1. The genome-wide rate of tumor MAE was
      higher than in previously described normal tissue and increased with specific
      tumor grade. Oncogenes, but not tumor suppressors, exhibited significantly higher
      MAE in high-grade compared with low-grade tumors. This method identified nine
      novel genes highly associated with MAE. Within cancer-related genes, MAE was gene
      specific; hTERT was most significantly affected, with a higher frequency of MAE
      in adult and advanced tumors. Clinically, MAE at TP53 exists only in mutated
      tumors and increases with tumor aggressiveness. MAE toward the normal allele at
      IDH1 conferred worse survival even in IDH1 mutated tumors. Taken together, our
      findings suggest that MAE is tumor and gene specific, frequent in brain tumor
      subtypes, and may be associated with tumor progression/aggressiveness. Further
      exploration of MAE at relevant genes may contribute to better understanding of
      tumor development and determine survival in brain tumor patients.

PMID- 22144471
TI  - Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer
      among premenopausal women.
AB  - Endogenous estrogens and estrogen metabolism are hypothesized to be associated
      with premenopausal breast cancer risk but evidence is limited. We examined 15
      urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal
      women in a case-control study nested within the Nurses' Health Study II (NHSII).
      From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal
      menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and
      June 2005 were matched to two controls each (N = 485). Urinary estrogen
      metabolites were measured by liquid chromatography-tandem mass spectrometry and
      adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals
      (CI) were estimated by multivariate conditional logistic regression. Higher
      urinary estrone and estradiol levels were strongly significantly associated with
      lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88;
      estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant,
      patterns also were observed with 2- and 4-hydroxylation pathway estrogen
      metabolites. Inverse associations generally were not observed with 16-pathway
      estrogen metabolites and a significant positive association was observed with 17
      epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) =
      0.01). In addition, there was a significant increased risk with higher 16
      pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99
      2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated
      with risk except parent estrogen metabolites/non-parent estrogen metabolites
      (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest
      that most mid-luteal urinary estrogen metabolite concentrations are not
      positively associated with breast cancer risk among premenopausal women. The
      inverse associations with parent estrogen metabolites and the parent estrogen
      metabolite/non-parent estrogen metabolite ratio suggest that women with higher
      urinary excretion of parent estrogens are at lower risk.

PMID- 22144472
TI  - The evolution of endothelial regulatory paradigms in cancer biology and vascular
      repair.
AB  - Although the roles of endothelial cells in cancer have primarily been considered
      to be related to tumor perfusion, the emerging appreciation of "angiocrine"
      regulation adds stromal regulatory capabilities to the expanding list of
      endothelial functions in tumors. We posit that an understanding of the state
      dependent paracrine regulatory paradigms established in vascular disease and
      repair will be critical for a deep understanding of tumor biology, as endothelial
      cells regulate diverse processes in all vascularized tissues. Here, we outline
      the historical developments that led to the appreciation of the paracrine
      regulatory functions of endothelial cells, summarize classical views of blood
      vessels and stroma in cancer, and attempt to merge these ideas to include the
      stromal regulatory endothelial cell as a critical regulator of cancer. The notion
      of the endothelial cell as a biochemical regulator of cancer state in constant
      dynamic balance with its tumor could impact diagnosis, prognosis, and treatment
      of cancer. Such concepts might well explain the mixed results from antiangiogenic
      cancer therapeutics and how certain drugs that improve vascular health correlate
      with improved cancer prognosis.

PMID- 22144473
TI  - Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and
      aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in
      the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
AB  - Studies that have examined the association between alcohol consumption and
      gastric cancer (GC) risk have been inconsistent. We conducted an investigation of
      29 genetic variants in alcohol metabolism loci (alcohol dehydrogenase, ADH1 gene
      cluster: ADH1A, ADH1B and ADH1C; ADH7 and aldehyde dehydrogenase, ALDH2), alcohol
      intake and GC risk. We analyzed data from a nested case-control study (364 cases
      and 1272 controls) within the European Prospective Investigation into Cancer and
      Nutrition cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a
      customized array. We observed a statistically significant association between a
      common 3'-flanking SNP near ADH1A (rs1230025) and GC risk [allelic odds ratio
      (OR)(A v T) = 1.30, 95% confidence interval (CI) = 1.07-1.59]. Two intronic
      variants, one in ADH1C (rs283411) and one in ALDH2 (rs16941667), also were
      associated with GC risk (OR(T v C) = 0.59; 95% CI = 0.38-0.91 and OR(T v C) =
      1.34; 95% CI = 1.00-1.79, respectively). Individuals carrying variant alleles at
      both ADH1 (rs1230025) and ALDH2 (rs16941667) were twice as likely to develop GC
      (OR(A+T) = 2.0; 95% CI = 1.25-3.20) as those not carrying variant alleles. The
      association between rs1230025 and GC was modified by alcohol intake (<5 g/day:
      OR(A) = 0.89, 95% CI = 0.57-1.39; >=5 g/day: OR(A) = 1.45, 95% CI = 1.08-1.94, P
      value = 0.05). The association was also modified by ethanol intake from beer. A
      known functional SNP in ADH1B (rs1229984) was associated with alcohol intake (P
      value = 0.04) but not GC risk. Variants in ADH7 were not associated with alcohol
      intake or GC risk. In conclusion, genetic variants at ADH1 and ALDH2 loci may
      influence GC risk, and alcohol intake may further modify the effect of ADH1
      rs1230025. Additional population-based studies are needed to confirm our results.

PMID- 22144474
TI  - Panoramic optical mapping shows wavebreak at a consistent anatomical site at the
      onset of ventricular fibrillation.
AB  - AIMS: The first seconds of ventricular fibrillation (VF) are well organized and
      can consist of just one to two rotating waves (rotors). New rotors are spawned
      when local propagation block causes wave fragmentation. We hypothesized that this
      process, which leads to fully developed VF, begins at a consistent anatomic site.
      METHODS AND RESULTS: We initiated VF with a stimulus timed to the local T-wave in
      10 isolated pig hearts. Hearts were stained with a voltage-sensitive dye and four
      video cameras recorded electrical propagation panoramically across the
      epicardium. In each VF episode, we identified the position of the first wavebreak
      event that produced new rotor(s) that persisted for at least one cycle. The first
      such wavebreak occurred along the anterior right ventricular insertion (ARVI) in
      26 of 32 VF episodes. In these episodes, wavebreak sites were 6 +/- 4 mm from the
      midline of the ARVI. In the remaining 6 episodes, wavebreak sites were 24 +/- 5
      mm from the midline on either the LV or RV. During rapid pacing, conduction speed
      was locally depressed at the ARVI when waves crossed parallel to the midline.
      Action potential duration (APD) was slightly longer (2.2 +/- 2.1 ms) at the ARVI
      compared with other sites (P< 0.01). Temporal APD alternans were small and not
      unique to the break site, suggesting that dynamic APD properties were not the
      cause of wavebreak. CONCLUSION: The ARVI is the dominant site for wavebreak at
      the onset of VF in normal myocardium. This may be due to the anatomic complexity
      of the region.

PMID- 22144475
TI  - Bacillus subtilis-mediated protection from Citrobacter rodentium-associated
      enteric disease requires espH and functional flagella.
AB  - Commensals limit disease caused by invading pathogens; however, the mechanisms
      and genes utilized by beneficial microbes to inhibit pathogenesis are poorly
      understood. The attaching and effacing mouse pathogen Citrobacter rodentium
      associates intimately with the intestinal epithelium, and infections result in
      acute colitis. C. rodentium is used to model the human pathogens
      enterohemorrhagic Escherichia coli and enteropathogenic E. coli. To confirm that
      Bacillus subtilis, a spore-forming bacterium found in the gut of mammals, could
      reduce C. rodentium-associated disease, mice received wild-type B. subtilis
      spores and 24 h later were infected by oral gavage with pathogenic C. rodentium.
      Disease was assessed by determining the extent of colonic epithelial hyperplasia,
      goblet cell loss, diarrhea, and pathogen colonization. Mice that received wild
      type B. subtilis prior to enteric infection were protected from disease even
      though C. rodentium colonization was not inhibited. In contrast, espH and hag
      mutants, defective in exopolysaccharides and flagellum production, respectively,
      did not protect mice from C. rodentium-associated disease. A motAB mutant also
      failed to protect mice from disease, suggesting that B. subtilis-mediated
      protection requires functional flagella. By expanding our current mechanistic
      knowledge of bacterial protection, we can better utilize beneficial microbes to
      prevent intestinal disease caused by pathogenic bacteria, ultimately reducing
      human disease. Our data demonstrate that wild-type B. subtilis reduced disease
      caused by C. rodentium infection through a mechanism that required espH and
      functional flagella.

PMID- 22144476
TI  - VimA-dependent modulation of acetyl coenzyme A levels and lipid A biosynthesis
      can alter virulence in Porphyromonas gingivalis.
AB  - The Porphyromonas gingivalis VimA protein has multifunctional properties that can
      modulate several of its major virulence factors. To further characterize VimA, P.
      gingivalis FLL406 carrying an additional vimA gene and a vimA-defective mutant in
      a different P. gingivalis genetic background were evaluated. The vimA-defective
      mutant (FLL451) in the P. gingivalis ATCC 33277 genetic background showed a
      phenotype similar to that of the vimA-defective mutant (FLL92) in the P.
      gingivalis W83 genetic background. In contrast to the wild type, gingipain
      activity was increased in P. gingivalis FLL406, a vimA chimeric strain. P.
      gingivalis FLL451 had a five times higher biofilm-forming capacity than the
      parent strain. HeLa cells incubated with P. gingivalis FLL92 showed a decrease in
      invasion, in contrast to P. gingivalis FLL451 and FLL406, which showed increases
      of 30 and 40%, respectively. VimA mediated coenzyme A (CoA) transfer to
      isoleucine and reduced branched-chain amino acid metabolism. The lipid A content
      and associated proteins were altered in the vimA-defective mutants. The VimA
      chimera interacted with several proteins which were found to have an LXXTG motif,
      similar to the sorting motif of gram-positive organisms. All the proteins had an
      N-terminal signal sequence with a putative sorting signal of L(P/T/S)X(T/N/D)G
      and two unique signatures of EXGXTX and HISXXGXG, in addition to a polar tail.
      Taken together, these observations further confirm the multifunctional role of
      VimA in modulating virulence possibly through its involvement in acetyl-CoA
      transfer and lipid A synthesis and possibly by protein sorting.

PMID- 22144478
TI  - Effect of inflammatory response on in vivo competition between two chlamydial
      variants in the guinea pig model of inclusion conjunctivitis.
AB  - In order to study the interaction of variants in in vivo infection, we employed
      an azithromycin-resistant mutant (AZ(2)) and its wild-type parent (SP(6)) in the
      guinea pig model of Chlamydia caviae conjunctival infection. When each strain was
      inoculated individually into conjunctiva, both attained the same level of growth,
      but AZ(2) elicited less pathology. However, when equal numbers of the two strains
      were inoculated together into the guinea pig conjunctiva, SP(6) produced a
      significantly greater number of inclusion-forming units than AZ(2), and the
      pathology reflected that of a SP(6) monoinfection. The goal of this study was to
      further characterize the dynamics of concomitant infection of these two distinct
      variants, with particular emphasis on the impact of the host response on the in
      vivo growth of each organism and the development of pathology. Animals infected
      with AZ(2) had reduced conjunctival infiltration with CD45(+) cells and
      neutrophils as well as a reduced interleukin-8 (IL-8) response. Gene expression
      of gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), CCL2,
      and CCL5 was also significantly lower in AZ(2)-infected animals. The lower
      inflammatory response induced by AZ(2) was associated with its decreased ability
      to activate NF-kappaB via Toll-like receptor 2 (TLR2). In general, the
      inflammatory response in animals infected with both variants was greater than in
      infection with AZ(2) alone, resulting in lower numbers of AZ(2) than those of
      SP(6) in the mixed infection. Our results suggest that the ability to elicit an
      inflammatory response is an important factor in the dynamics of mixed infection
      with strains that display different pathological phenotypes.

PMID- 22144477
TI  - Sialylation of lipooligosaccharides is dispensable for the virulence of
      Haemophilus ducreyi in humans.
AB  - Sialylated glycoconjugates on the surfaces of mammalian cells play important
      roles in intercellular communication and self-recognition. The sialic acid
      preferentially expressed in human tissues is N-acetylneuraminic acid (Neu5Ac). In
      a process called molecular mimicry, many bacterial pathogens decorate their cell
      surface glycolipids with Neu5Ac. Incorporation of Neu5Ac into bacterial
      glycolipids promotes bacterial interactions with host cell receptors called
      Siglecs. These interactions affect bacterial adherence, resistance to serum
      killing and phagocytosis, and innate immune responses. Haemophilus ducreyi, the
      etiologic agent of chancroid, expresses lipooligosaccharides (LOS) that are
      highly sialylated. However, an H. ducreyi sialyltransferase (lst) mutant, whose
      LOS contain reduced levels of Neu5Ac, is fully virulent in human volunteers.
      Recently, a second sialyltransferase gene (Hd0053) was discovered in H. ducreyi,
      raising the possibility that Hd0053 compensated for the loss of lst during human
      infection. CMP-Neu5Ac is the obligate nucleotide sugar donor for all bacterial
      sialyltransferases; LOS derived from an H. ducreyi CMP-Neu5Ac synthetase (neuA)
      mutant has no detectable Neu5Ac. Here, we compared an H. ducreyi neuA mutant to
      its wild-type parent in several models of pathogenesis. In human inoculation
      experiments, the neuA mutant formed papules and pustules at rates that were no
      different than those of its parent. When grown in media with and without Neu5Ac
      supplementation, the neuA mutant and its parent had similar phenotypes in
      bactericidal, macrophage uptake, and dendritic cell activation assays. Although
      we cannot preclude a contribution of LOS sialylation to ulcerative disease, these
      data strongly suggest that sialylation of LOS is dispensable for H. ducreyi
      pathogenesis in humans.

PMID- 22144479
TI  - Critical role of LuxS in the virulence of Campylobacter jejuni in a guinea pig
      model of abortion.
AB  - Previous studies on Campylobacter jejuni have demonstrated the role of LuxS in
      motility, cytolethal distending toxin production, agglutination, and intestinal
      colonization; however, its direct involvement in virulence has not been reported.
      In this study, we demonstrate a direct role of luxS in the virulence of C. jejuni
      in two different animal hosts. The IA3902 strain, a highly virulent sheep
      abortion strain recently described by our laboratory, along with its isogenic
      luxS mutant and luxS complement strains, was inoculated by the oral route into
      both a pregnant guinea pig virulence model and a chicken colonization model. In
      both cases, the IA3902 luxS mutant demonstrated a complete loss of ability to
      colonize the intestinal tract. In the pregnant model, the mutant also failed to
      induce abortion, while the wild-type strain was highly abortifacient. Genetic
      complementation of the luxS gene fully restored the virulent phenotype in both
      models. Interestingly, when the organism was inoculated into guinea pigs by the
      intraperitoneal route, no difference in virulence (abortion induction) was
      observed between the luxS mutant and the wild-type strain, suggesting that the
      defect in virulence following oral inoculation is likely associated with a defect
      in colonization and/or translocation of the organism out of the intestine. These
      studies provide the first direct evidence that LuxS plays an important role in
      the virulence of C. jejuni using an in vivo model of natural disease.

PMID- 22144480
TI  - Effects of amino acid supplementation on porin expression and ToxR levels in
      Vibrio cholerae.
AB  - Vibrio cholerae responds to environmental changes by altering the protein
      composition of its outer membrane. In rich medium, V. cholerae expresses almost
      exclusively the outer membrane porin OmpU, whereas in minimal medium, OmpT is the
      dominant porin. The supplementation of a minimal medium with a mixture of
      asparagine, arginine, glutamic acid, and serine (NRES) promotes OmpU production
      and OmpT repression at levels similar to those seen with rich media. Here we show
      that the altered Omp profile is not due to an increase in the growth rate in the
      presence of supplemental amino acids but requires the addition of specific amino
      acids. The effects of the NRES mix on Omp production were mediated by ToxR, a
      known regulator of omp gene expression. No changes in the Omp profile were
      detected in a toxR mutant. Supplementation with the NRES mix resulted in
      significantly higher levels of ToxR, and the elevated ToxR levels were sufficient
      to cause a switch in Omp synthesis. The increase in the level of the ToxR protein
      correlated with an increase in toxR mRNA levels and was observed only when toxR
      was expressed from its native promoter. ToxS, which is required for ToxR
      activity, was necessary for NRES-mediated omp gene regulation but not for the
      increase in ToxR levels. The growth of V. cholerae in the presence of bile acids
      also resulted in Omp switching, and this required ToxR. However, unlike the NRES
      mix, bile acids did not increase either ToxR protein or toxR mRNA levels,
      suggesting a different mechanism of omp gene regulation by bile than that by
      amino acids.

PMID- 22144481
TI  - Use of recombinase-based in vivo expression technology to characterize
      Enterococcus faecalis gene expression during infection identifies in vivo
      expressed antisense RNAs and implicates the protease Eep in pathogenesis.
AB  - Enterococcus faecalis is a member of the mammalian gastrointestinal microflora
      that has become a leading cause of nosocomial infections over the past several
      decades. E. faecalis must be able to adapt its physiology based on its
      surroundings in order to thrive in a mammalian host as both a commensal and a
      pathogen. We employed recombinase-based in vivo expression technology (RIVET) to
      identify promoters on the E. faecalis OG1RF chromosome that were specifically
      activated during the course of infection in a rabbit subdermal abscess model. The
      RIVET screen identified 249 putative in vivo-activated loci, over one-third of
      which are predicted to generate antisense transcripts. Three predicted antisense
      transcripts were detected in in vitro- and in vivo-grown cells, providing the
      first evidence of in vivo-expressed antisense RNAs in E. faecalis. Deletions in
      the in vivo-activated genes that encode glutamate 5-kinase (proB [EF0038]), the
      transcriptional regulator EbrA (ebrA [EF1809]), and the membrane metalloprotease
      Eep (eep [EF2380]) did not hinder biofilm formation in in vitro assays. In a
      rabbit model of endocarditis, the DeltaebrA strain was fully virulent, the
      DeltaproB strain was slightly attenuated, and the Deltaeep strain was severely
      attenuated. The Deltaeep virulence defect could be complemented by the expression
      of the wild-type gene in trans. Microscopic analysis of early Deltaeep biofilms
      revealed an abundance of small cellular aggregates that were not observed in wild
      type biofilms. This work illustrates the use of a RIVET screen to provide
      information about the temporal activation of genes during infection, resulting in
      the identification and confirmation of a new virulence determinant in an
      important pathogen.

PMID- 22144482
TI  - OmpT outer membrane proteases of enterohemorrhagic and enteropathogenic
      Escherichia coli contribute differently to the degradation of human LL-37.
AB  - Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) are
      food-borne pathogens that cause serious diarrheal diseases. To colonize the human
      intestine, these pathogens must overcome innate immune defenses such as
      antimicrobial peptides (AMPs). Bacterial pathogens have evolved various
      mechanisms to resist killing by AMPs, including proteolytic degradation of AMPs.
      To examine the ability of the EHEC and EPEC OmpT outer membrane (OM) proteases to
      degrade alpha-helical AMPs, ompT deletion mutants were generated. Determination
      of MICs of various AMPs revealed that both mutant strains are more susceptible
      than their wild-type counterparts to alpha-helical AMPs, although to different
      extents. Time course assays monitoring the degradation of LL-37 and C18G showed
      that EHEC cells degraded both AMPs faster than EPEC cells in an OmpT-dependent
      manner. Mass spectrometry analyses of proteolytic fragments showed that EHEC OmpT
      cleaves LL-37 at dibasic sites. The superior protection provided by EHEC OmpT
      compared to EPEC OmpT against alpha-helical AMPs was due to higher expression of
      the ompT gene and, in turn, higher levels of the OmpT protein in EHEC. Fusion of
      the EPEC ompT promoter to the EHEC ompT open reading frame resulted in decreased
      OmpT expression, indicating that transcriptional regulation of ompT is different
      in EHEC and EPEC. We hypothesize that the different contributions of EHEC and
      EPEC OmpT to the degradation and inactivation of LL-37 may be due to their
      adaptation to their respective niches within the host, the colon and small
      intestine, respectively, where the environmental cues and abundance of AMPs are
      different.

PMID- 22144483
TI  - Development and evaluation of an ovine antibody-based platform for treatment of
      Clostridium difficile infection.
AB  - Treatment of Clostridium difficile is a major problem as a hospital-associated
      infection which can cause severe, recurrent diarrhea. The currently available
      antibiotics are not effective in all cases and alternative treatments are
      required. In the present study, an ovine antibody-based platform for passive
      immunotherapy of C. difficile infection is described. Antibodies with high toxin
      neutralizing titers were generated against C. difficile toxins A and B and were
      shown to neutralize three sequence variants of these toxins (toxinotypes) which
      are prevalent in human C. difficile infection. Passive immunization of hamsters
      with a mixture of toxin A and B antibodies protected them from a challenge with
      C. difficile spores in a dose-dependent manner. Antibodies to both toxins A and B
      were required for protection. The administration of toxin A and B antibodies up
      to 24 h postchallenge was found to reduce significantly the onset of C. difficile
      infection compared to nonimmunized controls. Protection from infection was also
      demonstrated with key disease isolates (ribotypes 027 and 078), which are members
      of the hypervirulent C. difficile clade. The ribotype 027 and 078 strains also
      have the capacity to produce an active binary toxin and these data suggest that
      neutralization of this toxin is unnecessary for the management of infection
      induced by these strains. In summary, the data suggest that ovine toxin A and B
      antibodies may be effective in the treatment of C. difficile infection; their
      potential use for the management of severe, fulminant cases is discussed.

PMID- 22144484
TI  - Molecular mechanisms that mediate colonization of Shiga toxin-producing
      Escherichia coli strains.
AB  - Shiga toxin-producing Escherichia coli (STEC) is a group of pathogens which cause
      gastrointestinal disease in humans and have been associated with numerous food
      borne outbreaks worldwide. The intimin adhesin has been considered for many years
      to be the only colonization factor in these strains. However, the rapid progress
      in whole-genome sequencing of different STEC serotypes has accelerated the
      discovery of other adhesins (fimbrial and afimbrial), which have emerged as
      important contributors to the intestinal colonization occurring during STEC
      infection. This review summarizes recent progress to identify and characterize,
      at the molecular level, novel adhesion and colonization factors in STEC strains,
      with an emphasis on their contribution to virulence traits, their host-pathogen
      interactions, the regulatory mechanisms controlling their expression, and their
      role as targets eliciting immune responses in the host.

PMID- 22144485
TI  - Live attenuated Salmonella vaccines displaying regulated delayed lysis and
      delayed antigen synthesis to confer protection against Mycobacterium
      tuberculosis.
AB  - Live recombinant attenuated Salmonella vaccine (RASV) strains have great
      potential to induce protective immunity against Mycobacterium tuberculosis by
      delivering M. tuberculosis antigens. Recently, we reported that, in orally
      immunized mice, RASV strains delivering the M. tuberculosis early secreted
      antigenic target 6-kDa (ESAT-6) protein and culture filtrate protein 10 (CFP-10)
      antigens via the Salmonella type III secretion system (SopE amino-terminal region
      residues 1 to 80 with two copies of ESAT-6 and one copy of CFP-10 [SopE(Nt80)
      E2C]) afforded protection against aerosol challenge with M. tuberculosis. Here,
      we constructed and evaluated an improved Salmonella vaccine against M.
      tuberculosis. We constructed translational fusions for the synthesis of two
      copies of ESAT-6 plus CFP-10 fused to the OmpC signal sequence (OmpC(SS)-E2C) and
      amino acids 44 to 338 of antigen 85A (Ag85A(294)) flanked by the signal sequence
      (SS) and C-terminal peptide (CT) of beta-lactamase (Bla(SS)-Ag85A(294)-Bla(CT))
      to enable delivery via the Salmonella type II secretion system. The genes
      expressing these proteins were cloned as an operon transcribed from P(trc) into
      isogenic Asd(+)/MurA(+) pYA3681 lysis vector derivatives with different
      replication origins (pBR, p15A, pSC101), resulting in pYA4890, pYA4891, and
      pYA4892 for SopE(Nt80)-E2C/Ag85A(294) synthesis and pYA4893 and pYA4894 for
      OmpC(SS)-E2C/Ag85A(294) synthesis. Mice orally immunized with the RASV chi11021
      strain engineered to display regulated delayed lysis and regulated delayed
      antigen synthesis in vivo and harboring pYA4891, pYA4893, or pYA4894 elicited
      significantly greater humoral and cellular immune responses, and the RASV
      chi11021 strain afforded a greater degree of protection against M. tuberculosis
      aerosol challenge in mice than RASVs harboring any other Asd(+)/MurA(+) lysis
      plasmid and immunization with M. bovis BCG, demonstrating that RASV strains
      displaying regulated delayed lysis with delayed antigen synthesis resulted in
      highly immunogenic delivery vectors for oral vaccination against M. tuberculosis
      infection.

PMID- 22144486
TI  - Live attenuated Salmonella vaccines against Mycobacterium tuberculosis with
      antigen delivery via the type III secretion system.
AB  - Tuberculosis remains a global health threat, and there is dire need to develop a
      vaccine that is safe and efficacious and confers long-lasting protection. In this
      study, we constructed recombinant attenuated Salmonella vaccine (RASV) strains
      with plasmids expressing fusion proteins consisting of the 80 amino-terminal
      amino acids of the type 3 secretion system effector SopE of Salmonella and the
      Mycobacterium tuberculosis antigens early secreted antigenic target 6-kDa (ESAT
      6) protein and culture filtrate protein 10 (CFP-10). We demonstrated that the
      SopE-mycobacterial antigen fusion proteins were translocated into the cytoplasm
      of INT-407 cells in cell culture assays. Oral immunization of mice with RASV
      strains synthesizing SopE-ESAT-6-CFP-10 fusion proteins resulted in significant
      protection of the mice against aerosol challenge with M. tuberculosis H37Rv that
      was similar to the protection afforded by immunization with Mycobacterium bovis
      bacillus Calmette-Guerin (BCG) administered subcutaneously. In addition, oral
      immunization with the RASV strains specifying these mycobacterial antigens
      elicited production of significant antibody titers to ESAT-6 and production of
      ESAT-6- or CFP-10-specific gamma interferon (IFN-gamma)-secreting and tumor
      necrosis factor alpha (TNF-alpha)-secreting splenocytes.

PMID- 22144487
TI  - Free lipid A isolated from Porphyromonas gingivalis lipopolysaccharide is
      contaminated with phosphorylated dihydroceramide lipids: recovery in diseased
      dental samples.
AB  - Recent reports indicate that Porphyromonas gingivalis mediates alveolar bone loss
      or osteoclast modulation through engagement of Toll-like receptor 2 (TLR2),
      though the factors responsible for TLR2 engagement have yet to be determined.
      Lipopolysaccharide (LPS) and lipid A, lipoprotein, fimbriae, and phosphorylated
      dihydroceramides of P. gingivalis have been reported to activate host cell
      responses through engagement of TLR2. LPS and lipid A are the most controversial
      in this regard because conflicting evidence has been reported concerning the
      capacity of P. gingivalis LPS or lipid A to engage TLR2 versus TLR4. In the
      present study, we first prepared P. gingivalis LPS by the Tri-Reagent method and
      evaluated this isolate for contamination with phosphorylated dihydroceramide
      lipids. Next, the lipid A prepared from this LPS was evaluated for the presence
      of phosphorylated dihydroceramide lipids. Finally, we characterized the lipid A
      by the matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS)
      and electrospray-MS methods in order to quantify recovery of lipid A in lipid
      extracts from diseased teeth or subgingival plaque samples. Our results
      demonstrate that both the LPS and lipid A derived from P. gingivalis are
      contaminated with phosphorylated dihydroceramide lipids. Furthermore, the lipid
      extracts derived from diseased teeth or subgingival plaque do not contain free
      lipid A constituents of P. gingivalis but contain substantial amounts of
      phosphorylated dihydroceramide lipids. Therefore, the free lipid A of P.
      gingivalis is not present in measurable levels at periodontal disease sites. Our
      results also suggest that the TLR2 activation of host tissues attributed to LPS
      and lipid A of P. gingivalis could actually be mediated by phosphorylated
      dihydroceramides.

PMID- 22144488
TI  - Role of CD11b/CD18 in the process of intoxication by the adenylate cyclase toxin
      of Bordetella pertussis.
AB  - The adenylate cyclase toxin (ACT) of Bordetella pertussis does not require a
      receptor to generate intracellular cyclic AMP (cAMP) in a broad range of cell
      types. To intoxicate cells, ACT binds to the cell surface, translocates its
      catalytic domain across the cell membrane, and converts intracellular ATP to
      cAMP. In cells that express the integrin CD11b/CD18 (CR3), ACT is more potent
      than in CR3-negative cells. We find, however, that the maximum levels of cAMP
      accumulation inside CR3-positive and -negative cells are comparable. To better
      understand how CR3 affects the generation of cAMP, we used Chinese hamster ovary
      and K562 cells transfected to express CR3 and examined the steps in intoxication
      in the presence and absence of the integrin. The binding of ACT to cells is
      greater in CR3-expressing cells at all concentrations of ACT, and translocation
      of the catalytic domain is enhanced by CR3 expression, with ~80% of ACT molecules
      translocating their catalytic domain in CR3-positive cells but only 25% in CR3
      negative cells. Once in the cytosol, the unregulated catalytic domain converts
      ATP to cAMP, and at ACT concentrations >1,000 ng/ml, the intracellular ATP
      concentration is <5% of that in untreated cells, regardless of CR3 expression.
      This depletion of ATP prevents further production of cAMP, despite the CR3
      mediated enhancement of binding and translocation. In addition to characterizing
      the effects of CR3 on the actions of ACT, these data show that ATP consumption is
      yet another concentration-dependent activity of ACT that must be considered when
      studying how ACT affects target cells.

PMID- 22144489
TI  - Distinct compartmentalization of NF-kappaB activity in crypt and crypt-denuded
      lamina propria precedes and accompanies hyperplasia and/or colitis following
      bacterial infection.
AB  - Citrobacter rodentium induces transmissible murine colonic hyperplasia (TMCH) and
      variable degrees of inflammation and necrosis depending upon the genetic
      background. Utilizing C. rodentium-induced TMCH in C3H/HeNHsd inbred mice, we
      observed significant crypt hyperplasia on days 3 and 7 preceding active colitis.
      NF-kappaB activity in the crypt-denuded lamina propria (CLP) increased within 24
      h postinfection, followed by its activation in the crypts at day 3, which peaked
      by day 7. Increases in interleukin-alpha1 (IL-1alpha), IL-12(p40), and macrophage
      inflammatory protein 1alpha (MIP-1alpha) paralleled NF-kappaB activation, while
      increases in IL-1alpha/beta, IL-6/IL-12(p40)/granulocyte colony-stimulating
      factor (G-CSF)/keratinocyte-derived chemokine (KC)/monocyte chemotactic protein 1
      (MCP-1), and MIP-1alpha followed NF-kappaB activation leading to significant
      recruitment of neutrophils to the colonic mucosa and increased colonic
      myeloperoxidase (MPO) activity. Phosphorylation of the crypt cellular and nuclear
      p65 subunit at serines 276 and 536 led to functional NF-kappaB activation that
      facilitated expression of its downstream target, CXCL-1/KC, during TMCH. Distinct
      compartmentalization of phosphorylated extracellular signal-regulated kinase 1
      and 2 ([ERK1/2] Thr(180)/Tyr(182)) and p38 (Thr(202)/Tyr(204)) in the CLP
      preceded increases in the crypts. Inhibition of ERK1/2 and p38 suppressed NF
      kappaB activity in both crypts and the CLP. Dietary administration of 6% pectin
      or 4% curcumin in C. rodentium-infected mice also inhibited NF-kappaB activity
      and blocked CD3, F4/80, IL-1alpha/beta, G-CSF/MCP-1/KC, and MPO activity in the
      CLP while not affecting NF-kappaB activity in the crypts. Thus, distinct
      compartmentalization of NF-kappaB activity in the crypts and the CLP regulates
      crypt hyperplasia and/or colitis, and dietary intervention may be a novel
      strategy to modulate NF-kappaB-dependent protective immunity to facilitate crypt
      regeneration following C. rodentium-induced pathogenesis.

PMID- 22144491
TI  - Differential gene expression in mice infected with distinct Toxoplasma strains.
AB  - Toxoplasma gondii is the causative agent of toxoplasmosis in human and animals.
      In a mouse model, T. gondii strains can be divided into three groups, including
      the virulent, intermediately virulent, and nonvirulent. The clonal type I, II,
      and III T. gondii strains belong to these three groups, respectively. To better
      understand the basis of virulence phenotypes, we investigated mouse gene
      expression responses to the infection of different T. gondii strains at day 5
      after intraperitoneal inoculation with 500 tachyzoites. The transcriptomes of
      mouse peritoneal cells showed that 1,927, 1,573, and 1,009 transcripts were
      altered more than 2-fold by type I, II, and III infections, respectively, and
      that the majority of altered transcripts were shared. Overall transcription
      patterns were similar in type I and type II infections, and both had greater
      changes than infection with type III. Quantification of parasite burden in mouse
      spleens showed that the burden with type I infection was 1,000 times higher than
      that of type II and that the type II burden was 20 times higher than that of type
      III. Fluorescence-activated cell sorting revealed that type I and II infections
      had comparable macrophage populations, and both were higher than the population
      with type III infection. In addition, type I infection had a higher percentage of
      neutrophils than type II and III infections. Taken together, these results
      suggested that there is a common gene expression response to T. gondii infection
      in mice. This response is further modified by parasite strain-specific factors
      that determine their distinct virulence phenotypes.

PMID- 22144490
TI  - Enterohemorrhagic Escherichia coli virulence regulation by two bacterial
      adrenergic kinases, QseC and QseE.
AB  - The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 has two
      histidine sensor kinases, QseC and QseE, which respond to the mammalian
      adrenergic hormones epinephrine and norepinephrine by increasing their
      autophosphorylation. Although QseC and QseE are present in nonpathogenic strains
      of E. coli, EHEC exploits these kinases for virulence regulation. To further
      investigate the full extent of epinephrine and its sensors' impact on EHEC
      virulence, we performed transcriptomic and phenotypic analyses of single and
      double deletions of qseC and qseE genes in the absence or presence of
      epinephrine. We showed that in EHEC, epinephrine sensing seems to occur primarily
      through QseC and QseE. We also observed that QseC and QseE regulate expression of
      the locus of enterocyte effacement (LEE) genes positively and negatively,
      respectively. LEE activation, which is required for the formation of the
      characteristic attaching and effacing (A/E) lesions by EHEC on epithelial cells,
      is epinephrine dependent. Regulation of the LEE and the non-LEE-contained
      virulence factor gene nleA by QseE is indirect, through transcription inhibition
      of the RcsB response regulator. Finally, we show that coincubation of HeLa cells
      with epinephrine increases EHEC infectivity in a QseC- and QseE-dependent manner.
      These results genetically and phenotypically map the contributions of the two
      adrenergic sensors QseC and QseE to EHEC pathogenesis.

PMID- 22144492
TI  - Small intestinal intraepithelial lymphocytes expressing CD8 and T cell receptor
      gammadelta are involved in bacterial clearance during Salmonella enterica serovar
      Typhimurium infection.
AB  - The intestinal immune system is crucial for the maintenance of mucosal
      homeostasis and has evolved under the dual pressure of protecting the host from
      pathogenic infection and coexisting with the dense and diverse commensal
      organisms in the lumen. Intestinal intraepithelial lymphocytes (iIELs) are the
      first element of the host T cell compartment available to respond to oral
      infection by pathogens. This study demonstrated that oral infection by Salmonella
      enterica serovar Typhimurium promoted the expansion of iIELs, particularly CD8(+)
      TCRgammadelta(+) IELs, enhanced expression of NKG2D on iIELs, increased
      expression of MULT1, and decreased expression of Qa-1 by intestinal epithelial
      cells (IECs), leading to activation of, particularly, CD8(+) TCRgammadelta(+)
      iIELs and cytolytic activity against S. Typhimurium-infected IECs. Blockade of
      NKG2D recognition or depletion of TCRgammadelta(+) cells using a depleting
      monoclonal antibody significantly attenuated the clearance of S. Typhimurium in
      the intestine and other tissues. This study suggests that iIELs, particularly
      CD8(+) TCRgammadelta(+) iIELs, play important roles in the detection of
      pathogenic bacteria and eradication of infected epithelial cells and, thus,
      provide protection against invading pathogens. These data further our
      understanding of the mechanisms by which the immune system of the intestinal
      mucosa discriminates between pathogenic and commensal organisms.

PMID- 22144493
TI  - Roles of interleukin-17 in an experimental Legionella pneumophila pneumonia
      model.
AB  - Interleukin-17 (IL-17) is a key factor in T helper type 17 (Th17) lineage host
      responses and plays critical roles in immunological control of a variety of
      infectious diseases. Although Legionella pneumophila, an intracellular bacterium
      found widely in the environment, often causes a serious and life-threatening
      pneumonia in humans, the contribution of IL-17 to immune function during
      Legionella pneumonia is unknown. In the present study, we used an experimental
      Legionella pneumonia infection to clarify the role of IL-17 in the resulting
      immune response. We observed robust production of pulmonary IL-17A and IL-17F (IL
      17A/F), peaking on day 1 and declining thereafter. Upregulated production of
      tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-1beta, but not monocyte
      chemotactic protein 1 (MCP-1), was observed in Legionella-infected bone marrow
      derived macrophages from BALB/c mice that had been stimulated with IL-17A or IL
      17F. A significant decrease in the production of proinflammatory cytokines IL-6
      and TNF-alpha was observed in IL-17A/F-deficient mice (BALB/c background)
      infected with L. pneumophila. Moreover, we found impaired neutrophil migration
      and lower numbers of chemokines (KC, LIX, and MIP-2) in IL-17A/F-deficient mice.
      IL-17A/F-deficient mice also eliminated L. pneumophila more slowly and were less
      likely to survive a lethal challenge. These results demonstrate that IL-17A/F
      plays a critical role in L. pneumophila pneumonia, probably through induction of
      proinflammatory cytokines and accumulation of neutrophils at the infection site.

PMID- 22144494
TI  - Lsr2 peptides of Mycobacterium leprae show hierarchical responses in
      lymphoproliferative assays, with selective recognition by patients with anergic
      lepromatous leprosy.
AB  - Lsr2 protein of Mycobacterium leprae was shown earlier to elicit B and T cell
      responses in leprosy patients (20, 28). Lymphoproliferation to M. leprae and Lsr2
      antigens was observed in >70% of tuberculoid (T) patients and in 16 and 34% of
      lepromatous (L) patients, respectively. We focused on the M. leprae nonresponders
      in the lepromatous group using 22 synthetic Lsr2 peptides (end-to-end peptides A
      to F and overlapping peptides p1 to p16) in in vitro T cell responses. A total of
      125 leprosy and 13 tuberculosis patients and 19 healthy controls from the area of
      endemicity (here, healthy controls, or HC) were investigated. The highest
      responses were observed (67 to 100%) in HC for all peptides except p1 to p3, and
      the lowest was observed in tuberculosis patients. Significant differences in
      lymphoproliferation were observed in T, L, and HC groups (analysis of variance
      [ANOVA], P = 0.000 to 0.015) for all end-to-end peptides except B and for p5 and
      p7 to p10. Hierarchical recognition between lepromatous and tuberculoid leprosy
      was noted for p8 (P < 0.05) and between the HC and L groups for p7 to p10, p15,
      and p16 (P < 0.005 to P < 0.02). Significant lymphoproliferation was observed to
      peptides A to F and p1 to p9, p11, p12, p15, p16 (P = 0.000 to 0.001) with 40%
      responding to peptides C and p16 in L patients. Lepromatous patients also showed
      significantly higher levels of a gamma interferon (IFN-gamma) response to peptide
      C than to other peptides (P < 0.05). Major histocompatibility complex (MHC) class
      II bias for peptide recognition was not observed. These studies indicate that
      Lsr2 has multiple T cell epitopes that induce in vitro T cell responses in the
      highly infective lepromatous leprosy patients.

PMID- 22144495
TI  - Hematopoietic stem-progenitor cells restore immunoreactivity and improve survival
      in late sepsis.
AB  - Sepsis progresses from an early/acute hyperinflammatory to a late/chronic
      hypoinflammatory phase with immunosuppression. As a result of this phenotypic
      switch, mortality in late sepsis from persistent primary infection or
      opportunistic new infection often exceeds that in acute sepsis. Emerging data
      support that persistence of the hypoinflammatory (hyporesponsive) effector immune
      cells during late sepsis might involve alterations in myeloid
      differentiation/maturation that generate circulating repressor macrophages that
      do not readily clear active infection. Here, we used a cecal ligation and
      puncture (CLP) murine model of prolonged sepsis to show that adoptive transfer of
      CD34(+) hematopoietic stem-progenitor cells after CLP improves long-term survival
      by 65%. CD34(+) cell transfer corrected the immunosuppression of late sepsis by
      (i) producing significantly higher levels of proinflammatory mediators upon ex
      vivo stimulation with the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide,
      (ii) enhancing phagocytic activity of peritoneal macrophages, and (iii) clearing
      bacterial peritonitis. Improved immunity by CD34(+) cell transfer decreased
      inflammatory peritoneal exudate of surviving late-sepsis mice. Cell tracking
      experiments showed that the transferred CD34(+) cells first appeared in the bone
      marrow and then homed to the spleen and peritoneum. Because CD34(+) cells did not
      affect the early-phase hyperinflammatory response, it is likely that the newly
      incorporated pluripotent CD34(+) cells differentiated into competent immune cells
      in blood and tissue, thereby reversing or replacing the hyporesponsive endotoxin
      tolerant cells that occur and persist after the initiation of early sepsis.

PMID- 22144496
TI  - History of diabetes and risk of head and neck cancer: a pooled analysis from the
      international head and neck cancer epidemiology consortium.
AB  - BACKGROUND: A history of diabetes is associated with an increased risk of several
      types of cancers. Whether diabetes is a risk factor for head and neck cancer
      (HNC) has received little attention. METHODS: We pooled data from 12 case-control
      studies including 6,448 cases and 13,747 controls, and estimated OR and 95% CI
      for the associations between diabetes and HNC, adjusted for age, education level,
      sex, race/ethnicity, study center, cigarette smoking, alcohol use, and body mass
      index. RESULTS: We observed a weak association between diabetes and the incidence
      of HNC overall (OR, 1.09; 95% CI: 0.95-1.24). However, we observed a modest
      association among never smokers (OR, 1.59; 95% CI: 1.22-2.07), and no association
      among ever smokers (OR, 0.96; 95% CI: 0.83-1.11); likelihood ratio test for
      interaction P = 0.001. CONCLUSION: A history of diabetes was weakly associated
      with HNC overall, but we observed evidence of effect modification by smoking
      status, with a positive association among those who never smoked cigarettes.
      IMPACT: This study suggests that glucose metabolism abnormalities may be a HNC
      risk factor in subgroups of the population. Prospective studies incorporating
      biomarkers are needed to improve our understanding of the relationship between
      diabetes and HNC risk, possibly providing new strategies in the prevention of
      HNC.

PMID- 22144497
TI  - Assessing the clinical role of genetic markers of early-onset prostate cancer
      among high-risk men enrolled in prostate cancer early detection.
AB  - BACKGROUND: Men with familial prostate cancer and African American men are at
      risk for developing prostate cancer at younger ages. Genetic markers predicting
      early-onset prostate cancer may provide clinically useful information to guide
      screening strategies for high-risk men. We evaluated clinical information from
      six polymorphisms associated with early-onset prostate cancer in a longitudinal
      cohort of high-risk men enrolled in prostate cancer early detection with
      significant African American participation. METHODS: Eligibility criteria include
      ages 35 to 69 with a family history of prostate cancer or African American race.
      Participants undergo screening and biopsy per study criteria. Six markers
      associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24),
      rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)]
      were genotyped. Cox models were used to evaluate time to prostate cancer
      diagnosis and prostate-specific antigen (PSA) prediction for prostate cancer by
      genotype. Harrell's concordance index was used to evaluate predictive accuracy
      for prostate cancer by PSA and genetic markers. RESULTS: Four hundred and sixty
      participants with complete data and >= 1 follow-up visit were included. Fifty-six
      percent were African American. Among African American men, rs6983561 genotype was
      significantly associated with earlier time to prostate cancer diagnosis (P =
      0.005) and influenced prediction for prostate cancer by the PSA (P < 0.001). When
      combined with PSA, rs6983561 improved predictive accuracy for prostate cancer
      compared with PSA alone among African American men (PSA = 0.57 vs. PSA +
      rs6983561 = 0.75, P = 0.03). CONCLUSIONS: Early-onset marker rs6983561 adds
      potentially useful clinical information for African American men undergoing
      prostate cancer risk assessment. Further study is warranted to validate these
      findings. IMPACT: Genetic markers of early-onset prostate cancer have potential
      to refine and personalize prostate cancer early detection for high-risk men.

PMID- 22144498
TI  - Unmet challenges in cancer disparities--letter.

PMID- 22144500
TI  - A population-based study of prevalence and adherence trends in average risk
      colorectal cancer screening, 1997 to 2008.
AB  - BACKGROUND: Increasing colorectal cancer screening (CRCS) is important for
      attaining the Healthy People 2020 goal of reducing CRC-related morbidity and
      mortality. Evaluating CRCS trends can help identify shifts in CRCS, and specific
      groups that might be targeted for CRCS. METHODS: We utilized medical records to
      describe population-based adherence to average-risk CRCS guidelines from 1997 to
      2008 in Olmsted County, MN. CRCS trends were analyzed overall and by gender, age,
      and adherence to screening mammography (women only). We also carried out an
      analysis to examine whether CRCS is being initiated at the recommended age of 50.
      RESULTS: From 1997 to 2008, the size of the total eligible sample ranged from
      20,585 to 21,468 people. CRCS increased from 22% to 65% for women and from 17% to
      59% for men (P < 0.001 for both) between 1997 and 2008. CRCS among women current
      with mammography screening increased from 26% to 74%, and this group was more
      likely to be adherent to CRCS than all other subgroups analyzed (P < 0.001).The
      mean ages of screening initiation were stable throughout the study period, with a
      mean age of 55 years among both men and women in 2008. CONCLUSION: Although
      overall CRCS tripled during the study period, there is still room for
      improvement. IMPACT: Working to decrease the age at first screening, exploration
      of gender differences in screening behavior, and targeting women adherent to
      mammography but not to CRCS seem warranted.

PMID- 22144501
TI  - Is the accuracy of self-reported colorectal cancer screening associated with
      social desirability?
AB  - BACKGROUND: Self-reported cancer screening behaviors are often overreported and
      may lead to biased estimates of prevalence and of subgroup differences in
      screening. We examined whether the tendency to give socially desirable responses
      was associated with concordance between self-reported colorectal cancer (CRC)
      screening behaviors and medical records. METHODS: Primary care patients (n = 857)
      age 50 to 74 years completed a mail, face-to-face, or telephone survey that
      assessed CRC screening and social desirability measured by a short version of the
      Marlowe-Crowne scale. We used medical records to verify self-reports of fecal
      occult blood testing (FOBT), sigmoidoscopy, colonoscopy, and barium enema.
      RESULTS: Social desirability scores were lower for whites versus African
      Americans, college graduates, and patients reporting no prior screening tests;
      they were higher for telephone versus mail or face-to-face survey respondents. In
      univariable logistic regression analysis, social desirability scores were not
      associated with concordance for FOBT (OR = 1.03, 95% CI = 0.94-1.13),
      sigmoidoscopy (OR = 0.95, 95% CI = 0.86-1.04), or colonoscopy (OR = 0.99, 95% CI
      = 0.88-1.11); however, lower social desirability scores were associated with
      increased concordance for barium enema (OR = 0.87, 95% CI = 0.77-0.99). In
      multivariable analyses, no associations were statistically significant.
      CONCLUSION: Social desirability as measured by the Marlowe-Crowne scale was not
      associated with accuracy of self-reported CRC tests in our sample, suggesting
      that other explanations for overreporting need to be explored. IMPACT: By
      understanding sources of response bias, we can improve the accuracy of self
      report measures.

PMID- 22144502
TI  - Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15): a potential screening tool
      for the prevention of colon cancer?
AB  - BACKGROUND: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) mediates nonsteroidal
      anti-inflammatory drug (NSAID) protection from colonic polyps in mice and is
      linked to the development of colorectal carcinoma in humans. Therefore, changes
      in serum MIC-1/GDF15 levels could predict the presence of premalignant colonic
      polyposis and assist in population screening strategies. METHODS: Serum MIC
      1/GDF15 levels were measured in subjects in the Polyp Prevention Trial, in which
      NSAID use and colon cancer risk factors were defined. Subjects had an initial
      adenoma removed, a repeat colonoscopy removing previously unidentified polyps,
      and serum MIC-1/GDF15 estimation. Three years later recurrent adenomas were
      identified and serum MIC-1/GDF15 levels reestimated. The relationship between
      serum MIC-1/GDF15 levels and adenoma presence or recurrence was examined.
      RESULTS: Serum MIC-1/GDF15 levels differed by adenoma status and were
      significantly related to colon cancer risk factors. In addition, mean serum MIC
      1/GDF15 levels rose with increasing numbers of adenomas present and high-risk
      adenoma recurrence. NSAID users had higher serum MIC-1/GDF15 concentrations,
      which were related to protection from adenoma recurrence. Furthermore, adjusted
      serum MIC-1/GDF15 levels at final follow-up were related to adenoma recurrence
      (highest quartile MIC-1/GDF15; OR = 14.7, 95% CI: 3.0-73). CONCLUSIONS: These
      data suggest that MIC-1/GDF15 mediates at least some of the protection afforded
      by NSAIDs against human colonic polyposis. Furthermore, serum MIC-1/GDF15 levels
      vary with the development of adnenomatous colonic polyps. IMPACT: Serum MIC
      1/GDF15 determination may hold promise as the first serum screening test to
      assist the detection of premalignant adenomatous colonic polyposis.

PMID- 22144503
TI  - The impact of obesity on follow-up after an abnormal screening mammogram.
AB  - BACKGROUND: Effective breast cancer screening and early detection are crucial for
      obese women, who experience a higher incidence of the disease and present at
      later stages. METHODS: We examined the association between body mass index (BMI)
      and timeliness of follow-up after 241,222 abnormal screening mammograms carried
      out on 201,470 women in the Breast Cancer Surveillance Consortium. Each mammogram
      had one of three recommendations for follow-up: short-interval follow-up,
      immediate additional diagnostic imaging, and biopsy/surgical consultation. We
      used logistic regression to estimate the adjusted effect of BMI on any recorded
      follow-up within 270 days of the recommendation; linear regression was used to
      model the mean follow-up time among those with recorded follow-up. RESULTS: As
      compared with normal-weight women, higher BMI was associated with slightly
      increased odds of follow-up among women who received a recommendation for short
      interval follow-up (ORs: 1.03-1.10; P = 0.04) or immediate additional imaging
      (ORs: 1.03-1.09; P = 0.01). No association was found for biopsy/surgical
      consultation recommendations (P = 0.90). Among those with recorded follow-up,
      higher BMI was associated with longer mean time to follow-up for both short
      interval (3-10 days; P < 0.001) and additional imaging recommendations (2-3 days;
      P < 0.001) but not biopsy/surgical consultation (P = 0.06). Regardless of
      statistical significance, actual differences in days to follow-up across BMI
      groups were small and unlikely to be clinically significant. CONCLUSIONS: Once
      obese women access screening mammography, their follow-up after abnormal results
      is similar to that of normal-weight women. IMPACT: Efforts to improve early
      detection of breast cancer in obese women should focus elsewhere, such as
      improving participation in screening mammography.

PMID- 22144504
TI  - Polymorphic variation in the GC and CASR genes and associations with vitamin D
      metabolite concentration and metachronous colorectal neoplasia.
AB  - BACKGROUND: Vitamin D levels and calcium intake have been associated with risk of
      colorectal neoplasia, and genetic variation in vitamin D pathway genes may affect
      circulating vitamin D metabolite concentrations and/or risk for colorectal
      lesions. This study evaluated associations between polymorphic variation in the
      Gc-globulin (GC) and calcium-sensing receptor (CASR) and odds for metachronous
      colorectal neoplasia and vitamin D metabolite concentrations. METHODS:
      Participants from the Ursodeoxycholic Acid (UDCA) and Wheat Bran Fiber (WBF)
      trials (n = 1,439) were analyzed using a single-nucleotide polymorphism (SNP)
      tagging approach, with a subset (n = 404) of UDCA trial participants for whom
      vitamin D metabolite concentrations were also available. A total of 25 GC and 35
      CASR tagSNPs were evaluated using multiple statistical methods. RESULTS:
      Principal components analyses did not reveal gene-level associations between GC
      or CASR and colorectal neoplasia; however, a significant gene-level association
      between GC and 25(OH)D concentrations (P < 0.01) was observed. At the individual
      SNP level and following multiple comparisons adjustments, significant
      associations were observed between seven GC (rs7041, rs222035, rs842999,
      rs1155563, rs12512631, rs16846876, and rs1746825) polymorphisms and circulating
      measures of 25(OH)D (adjusted P < 0.01) and CASR SNP rs1042636 and proximal
      colorectal neoplasia (adjusted P = 0.01). CONCLUSIONS: These results show a
      possible association between variation in CASR and odds of colorectal neoplasia
      as well as the potential role of variation in GC with circulating 25(OH)D
      concentrations. IMPACT: Additional research is warranted to determine the
      mechanism of GC genotype in influencing 25(OH)D concentrations and to further
      elucidate the role of CASR in colorectal neoplasia.

PMID- 22144507
TI  - International conference on multimodality imaging.

PMID- 22144508
TI  - Scientific journals and impact factors.

PMID- 22144499
TI  - Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers:
      results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
AB  - BACKGROUND: Previously, small studies have found that BRCA1 and BRCA2 breast
      tumors differ in their pathology. Analysis of larger datasets of mutation
      carriers should allow further tumor characterization. METHODS: We used data from
      4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of
      invasive breast, ovarian, and contralateral breast cancers. RESULTS: There was
      strong evidence that the proportion of estrogen receptor (ER)-negative breast
      tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 * 10(-5)), but
      increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 * 10(-6)).
      The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1
      carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and
      BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER
      positive tumors (grade 3 vs. grade 1; P = 1.2 * 10(-13) for BRCA1 and P = 0.001
      for BRCA2). ER and progesterone receptor (PR) expression were independently
      associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 =
      9.4, 95% CI: 7.0-12.6 and PR-positive OR = 1.7, 95% CI: 1.3-2.3, under joint
      analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 =
      3.3, 95% CI: 2.4-4.4; P = 4.4 * 10(-14)), and medullary tumors BRCA1-related (OR
      for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 * 10(-15)). ER-status of the first
      breast cancer was predictive of ER-status of asynchronous contralateral breast
      cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant
      differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers
      (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%).
      CONCLUSIONS/IMPACT: Pathologic characteristics of BRCA1 and BRCA2 tumors may be
      useful for improving risk-prediction algorithms and informing clinical strategies
      for screening and prophylaxis.

PMID- 22144506
TI  - An approach for balancing diagnostic image quality with cancer risk: application
      to pediatric diagnostic imaging of 99mTc-dimercaptosuccinic acid.
AB  - A recent survey of pediatric hospitals showed a large variability in the activity
      administered for diagnostic nuclear medicine imaging of children. Imaging
      guidelines, especially for pediatric patients, must balance the risks associated
      with radiation exposure with the need to obtain the high-quality images necessary
      to derive the benefits of an accurate clinical diagnosis. METHODS:
      Pharmacokinetic modeling and a pediatric series of nonuniform rational B-spline
      based phantoms have been used to simulate (99m)Tc-dimercaptosuccinic acid SPECT
      images. Images were generated for several different administered activities and
      for several lesions with different target-to-background activity concentration
      ratios; the phantoms were also used to calculate organ S values for (99m)Tc.
      Channelized Hotelling observer methodology was used in a receiver-operating
      characteristic analysis of the diagnostic quality of images with different
      modeled administered activities (i.e., count densities) for anthropomorphic
      reference phantoms representing two 10-y-old girls with equal weights but
      different body morphometry. S value-based dosimetry was used to calculate the
      mean organ-absorbed doses to the 2 pediatric patients. Using BEIR VII age- and
      sex-specific risk factors, we converted absorbed doses to excess risk of cancer
      incidence and used them to directly assess the risk of the procedure. RESULTS:
      Combined, these data provided information about the tradeoff between cancer risk
      and diagnostic image quality for 2 phantoms having the same weight but different
      body morphometry. The tradeoff was different for the 2 phantoms, illustrating
      that weight alone may not be sufficient for optimally scaling administered
      activity in pediatric patients. CONCLUSION: The study illustrates implementation
      of a rigorous approach for balancing the benefits of adequate image quality
      against the radiation risks and also demonstrates that weight-based adjustment to
      the administered activity is suboptimal. Extension of this methodology to other
      radiopharmaceuticals would yield the data required to generate objective and well
      founded administered activity guidelines for pediatric and other patients.

PMID- 22144509
TI  - SNM 2020 Task Force Assesses Environment for Profession, Society.

PMID- 22144511
TI  - Koral receives 2011 Loevinger-Berman Award.

PMID- 22144512
TI  - A name change for the Society: perspectives.

PMID- 22144513
TI  - A check-up on SNM's financial health.

PMID- 22144514
TI  - MITA PET coverage workshop.

PMID- 22144517
TI  - Two efficient solutions for visual odometry using directional correspondence.
AB  - This paper presents two new, efficient solutions to the two-view, relative pose
      problem from three image point correspondences and one common reference
      direction. This three-plus-one problem can be used either as a substitute for the
      classic five-point algorithm, using a vanishing point for the reference
      direction, or to make use of an inertial measurement unit commonly available on
      robots and mobile devices where the gravity vector becomes the reference
      direction. We provide a simple, closed-form solution and a solution based on
      algebraic geometry which offers numerical advantages. In addition, we introduce a
      new method for computing visual odometry with RANSAC and four point
      correspondences per hypothesis. In a set of real experiments, we demonstrate the
      power of our approach by comparing it to the five-point method in a hypothesize
      and-test visual odometry setting.

PMID- 22144516
TI  - Discriminative latent models for recognizing contextual group activities.
AB  - In this paper, we go beyond recognizing the actions of individuals and focus on
      group activities. This is motivated from the observation that human actions are
      rarely performed in isolation; the contextual information of what other people in
      the scene are doing provides a useful cue for understanding high-level
      activities. We propose a novel framework for recognizing group activities which
      jointly captures the group activity, the individual person actions, and the
      interactions among them. Two types of contextual information, group-person
      interaction and person-person interaction, are explored in a latent variable
      framework. In particular, we propose three different approaches to model the
      person-person interaction. One approach is to explore the structures of person
      person interaction. Differently from most of the previous latent structured
      models, which assume a predefined structure for the hidden layer, e.g., a tree
      structure, we treat the structure of the hidden layer as a latent variable and
      implicitly infer it during learning and inference. The second approach explores
      person-person interaction in the feature level. We introduce a new feature
      representation called the action context (AC) descriptor. The AC descriptor
      encodes information about not only the action of an individual person in the
      video, but also the behavior of other people nearby. The third approach combines
      the above two. Our experimental results demonstrate the benefit of using
      contextual information for disambiguating group activities.

PMID- 22144518
TI  - Learning Hybrid Image Templates (HIT) by Information Projection.
AB  - This paper presents a novel framework for learning a generative image
      representation-the hybrid image template (HIT) from a small number (i.e., 3 ?sim
      20) of image examples. Each learned template is composed of, typically, 50 ?sim
      500 image patches whose geometric attributes (location, scale, orientation) may
      adapt in a local neighborhood for deformation, and whose appearances are
      characterized, respectively, by four types of descriptors: local sketch (edge or
      bar), texture gradients with orientations, flatness regions, and colors. These
      heterogeneous patches are automatically ranked and selected from a large pool
      according to their information gains using an information projection framework.
      Intuitively, a patch has a higher information gain if 1) its feature statistics
      are consistent within the training examples and are distinctive from the
      statistics of negative examples (i.e., generic images or examples from other
      categories); and 2) its feature statistics have less intraclass variations. The
      learning process pursues the most informative (for either generative or
      discriminative purpose) patches one at a time and stops when the information gain
      is within statistical fluctuation. The template is associated with a well
      normalized probability model that integrates the heterogeneous feature
      statistics. This automated feature selection procedure allows our algorithm to
      scale up to a wide range of image categories, from those with regular shapes to
      those with stochastic texture. The learned representation captures the intrinsic
      characteristics of the object or scene categories. We evaluate the hybrid image
      templates on several public benchmarks, and demonstrate classification
      performances on par with state-of-the-art methods like HoG+SVM, and when small
      training sample sizes are used, the proposed system shows a clear advantage. 

PMID- 22144519
TI  - Trainable Convolution Filters and Their Application to Face Recognition.
AB  - In this paper, we present a novel image classification system that is built
      around a core of trainable filter ensembles that we call Volterra kernel
      classifiers. Our system treats images as a collection of possibly overlapping
      patches and is composed of three components: (1) A scheme for a single patch
      classification that seeks a smooth, possibly nonlinear, functional mapping of the
      patches into a range space, where patches of the same class are close to one
      another, while patches from different classes are far apart-in the L_2 sense.
      This mapping is accomplished using trainable convolution filters (or Volterra
      kernels) where the convolution kernel can be of any shape or order. (2) Given a
      corpus of Volterra classifiers with various kernel orders and shapes for each
      patch, a boosting scheme for automatically selecting the best weighted
      combination of the classifiers to achieve higher per-patch classification rate.
      (3) A scheme for aggregating the classification information obtained for each
      patch via voting for the parent image classification. We demonstrate the
      effectiveness of the proposed technique using face recognition as an application
      area and provide extensive experiments on the Yale, CMU PIE, Extended Yale B,
      Multi-PIE, and MERL Dome benchmark face data sets. We call the Volterra kernel
      classifiers applied to face recognition Volterrafaces. We show that our
      technique, which falls into the broad class of embedding-based face image
      discrimination methods, consistently outperforms various state-of-the-art methods
      in the same category. 

PMID- 22144520
TI  - Difference-Based Image Noise Modeling Using Skellam Distribution.
AB  - By the laws of quantum physics, pixel intensity does not have a true value, but
      should be a random variable. Contrary to the conventional assumptions, the
      distribution of intensity may not be an additive Gaussian. We propose to directly
      model the intensity difference and show its validity by an experimental
      comparison to the conventional additive model. As a model of the intensity
      difference, we present a Skellam distribution derived from the Poisson photon
      noise model. This modeling induces a linear relationship between intensity and
      Skellam parameters, while conventional variance computation methods do not yield
      any significant relationship between these parameters under natural illumination.
      The intensity-Skellam line is invariant to scene, illumination, and even most of
      camera parameters. We also propose practical methods to obtain the line using a
      color pattern and an arbitrary image under natural illumination. Because the
      Skellam parameters that can be obtained from this linearity determine a noise
      distribution for each intensity value, we can statistically determine whether any
      intensity difference is caused by an underlying signal difference or by noise. We
      demonstrate the effectiveness of this new noise model by applying it to practical
      applications of background subtraction and edge detection. 

PMID- 22144521
TI  - Elastic geodesic paths in shape space of parameterized surfaces.
AB  - This paper presents a novel Riemannian framework for shape analysis of
      parameterized surfaces. In particular, it provides efficient algorithms for
      computing geodesic paths which, in turn, are important for comparing, matching,
      and deforming surfaces. The novelty of this framework is that geodesics are
      invariant to the parameterizations of surfaces and other shape-preserving
      transformations of surfaces. The basic idea is to formulate a space of embedded
      surfaces (surfaces seen as embeddings of a unit sphere in IR3) and impose a
      Riemannian metric on it in such a way that the reparameterization group acts on
      this space by isometries. Under this framework, we solve two optimization
      problems. One, given any two surfaces at arbitrary rotations and
      parameterizations, we use a path-straightening approach to find a geodesic path
      between them under the chosen metric. Second, by modifying a technique presented
      in [25], we solve for the optimal rotation and parameterization (registration)
      between surfaces. Their combined solution provides an efficient mechanism for
      computing geodesic paths in shape spaces of parameterized surfaces. We illustrate
      these ideas using examples from shape analysis of anatomical structures and other
      general surfaces.

PMID- 22144522
TI  - Toward Holistic Scene Understanding: Feedback Enabled Cascaded Classification
      Models.
AB  - Scene understanding includes many related subtasks, such as scene categorization,
      depth estimation, object detection, etc. Each of these subtasks is often
      notoriously hard, and state-of-the-art classifiers already exist for many of
      them. These classifiers operate on the same raw image and provide correlated
      outputs. It is desirable to have an algorithm that can capture such correlation
      without requiring any changes to the inner workings of any classifier. We propose
      Feedback Enabled Cascaded Classification Models (FE-CCM), that jointly optimizes
      all the subtasks while requiring only a "black box" interface to the original
      classifier for each subtask. We use a two-layer cascade of classifiers, which are
      repeated instantiations of the original ones, with the output of the first layer
      fed into the second layer as input. Our training method involves a feedback step
      that allows later classifiers to provide earlier classifiers information about
      which error modes to focus on. We show that our method significantly improves
      performance in all the subtasks in the domain of scene understanding, where we
      consider depth estimation, scene categorization, event categorization, object
      detection, geometric labeling, and saliency detection. Our method also improves
      performance in two robotic applications: an object-grasping robot and an object
      finding robot. 

PMID- 22144523
TI  - CPMC: Automatic Object Segmentation Using Constrained Parametric Min-Cuts.
AB  - We present a novel framework to generate and rank plausible hypotheses for the
      spatial extent of objects in images using bottom-up computational processes and
      mid-level selection cues. The object hypotheses are represented as figure-ground
      segmentations, and are extracted automatically, without prior knowledge of the
      properties of individual object classes, by solving a sequence of Constrained
      Parametric Min-Cut problems (CPMC) on a regular image grid. In a subsequent step,
      we learn to rank the corresponding segments by training a continuous model to
      predict how likely they are to exhibit real-world regularities (expressed as
      putative overlap with ground truth) based on their mid-level region properties,
      then diversify the estimated overlap score using maximum marginal relevance
      measures. We show that this algorithm significantly outperforms the state of the
      art for low-level segmentation in the VOC 2009 and 2010 data sets. In our
      companion papers [1], [2], we show that the algorithm can be used, successfully,
      in a segmentation-based visual object category recognition pipeline. This
      architecture ranked first in the VOC2009 and VOC2010 image segmentation and
      labeling challenges. 

PMID- 22144524
TI  - Unsupervised image matching based on manifold alignment.
AB  - This paper challenges the issue of automatic matching between two image sets with
      similar intrinsic structures and different appearances, especially when there is
      no prior correspondence. An unsupervised manifold alignment framework is proposed
      to establish correspondence between data sets by a mapping function in the mutual
      embedding space. We introduce a local similarity metric based on parameterized
      distance curves to represent the connection of one point with the rest of the
      manifold. A small set of valid feature pairs can be found without manual
      interactions by matching the distance curve of one manifold with the curve
      cluster of the other manifold. To avoid potential confusions in image matching,
      we propose an extended affine transformation to solve the nonrigid alignment in
      the embedding space. The comparatively tight alignments and the structure
      preservation can be obtained simultaneously. The point pairs with the minimum
      distance after alignment are viewed as the matchings. We apply manifold alignment
      to image set matching problems. The correspondence between image sets of
      different poses, illuminations, and identities can be established effectively by
      our approach.

PMID- 22144525
TI  - Polynomial Eigenvalue Solutions to Minimal Problems in Computer Vision.
AB  - We present a method for solving systems of polynomial equations appearing in
      computer vision. This method is based on polynomial eigenvalue solvers and is
      more straightforward and easier to implement than the state-of-the-art Grobner
      basis method since eigenvalue problems are well studied, easy to understand, and
      efficient and robust algorithms for solving these problems are available. We
      provide a characterization of problems that can be efficiently solved as
      polynomial eigenvalue problems (PEPs) and present a resultant-based method for
      transforming a system of polynomial equations to a polynomial eigenvalue problem.
      We propose techniques that can be used to reduce the size of the computed
      polynomial eigenvalue problems. To show the applicability of the proposed
      polynomial eigenvalue method, we present the polynomial eigenvalue solutions to
      several important minimal relative pose problems. 

PMID- 22144526
TI  - Interactive slice WIM: navigating and interrogating volume data sets using a
      multisurface, multitouch VR interface.
AB  - We present Interactive Slice World-in-Miniature (WIM), a framework for navigating
      and interrogating volumetric data sets using an interface enabled by a virtual
      reality environment made of two display surfaces: an interactive multitouch
      table, and a stereoscopic display wall. The framework addresses two current
      challenges in immersive visualization: 1) providing an appropriate
      overview+detail style of visualization while navigating through volume data, and
      2) supporting interactive querying and data exploration, i.e., interrogating
      volume data. The approach extends the WIM metaphor, simultaneously displaying a
      large-scale detailed data visualization and an interactive miniature. Leveraging
      the table+wall hardware, horizontal slices are projected (like a shadow) down
      onto the table surface, providing a useful 2D data overview to complement the 3D
      views as well as a data context for interpreting 2D multitouch gestures made on
      the table. In addition to enabling effective navigation through complex
      geometries, extensions to the core Slice WIM technique support interacting with a
      set of multiple slices that persist on the table even as the user navigates
      around a scene and annotating and measuring data via points, paths, and volumes
      specified using interactive slices. Applications of the interface to two volume
      data sets are presented, and design decisions, limitations, and user feedback are
      discussed.

PMID- 22144527
TI  - Real-time rendering of rough refraction.
AB  - We present an algorithm to render objects made of transparent materials with
      rough surfaces in real-time, under all-frequency distant illumination. Rough
      surfaces cause wide scattering as light enters and exits objects, which
      significantly complicates the rendering of such materials. We present two
      contributions to approximate the successive scattering events at interfaces, due
      to rough refraction: First, an approximation of the Bidirectional Transmittance
      Distribution Function (BTDF), using spherical Gaussians, suitable for real-time
      estimation of environment lighting using preconvolution; second, a combination of
      cone tracing and macrogeometry filtering to efficiently integrate the scattered
      rays at the exiting interface of the object. We demonstrate the quality of our
      approximation by comparison against stochastic ray tracing. Furthermore we
      propose two extensions to our method for supporting spatially varying roughness
      on object surfaces and local lighting for thin objects.

PMID- 22144528
TI  - Multimodal Data Fusion Based on Mutual Information.
AB  - Multimodal visualization aims at fusing different data sets so that the resulting
      combination provides more information and understanding to the user. To achieve
      this aim, we propose a new information-theoretic approach that automatically
      selects the most informative voxels from two volume data sets. Our fusion
      criteria are based on the information channel created between the two input data
      sets that permit us to quantify the information associated with each intensity
      value. This specific information is obtained from three different ways of
      decomposing the mutual information of the channel. In addition, an assessment
      criterion based on the information content of the fused data set can be used to
      analyze and modify the initial selection of the voxels by weighting the
      contribution of each data set to the final result. The proposed approach has been
      integrated in a general framework that allows for the exploration of volumetric
      data models and the interactive change of some parameters of the fused data set.
      The proposed approach has been evaluated on different medical data sets with very
      promising results. 

PMID- 22144529
TI  - Empirical Studies in Information Visualization: Seven Scenarios.
AB  - We take a new, scenario-based look at evaluation in information visualization.
      Our seven scenarios, evaluating visual data analysis and reasoning, evaluating
      user performance, evaluating user experience, evaluating environments and work
      practices, evaluating communication through visualization, evaluating
      visualization algorithms, and evaluating collaborative data analysis were derived
      through an extensive literature review of over 800 visualization publications.
      These scenarios distinguish different study goals and types of research questions
      and are illustrated through example studies. Through this broad survey and the
      distillation of these scenarios, we make two contributions. One, we encapsulate
      the current practices in the information visualization research community and,
      two, we provide a different approach to reaching decisions about what might be
      the most effective evaluation of a given information visualization. Scenarios can
      be used to choose appropriate research questions and goals and the provided
      examples can be consulted for guidance on how to design one's own study. 

PMID- 22144530
TI  - Precomputed Safety Shapes for Efficient and Accurate Height-Field Rendering.
AB  - Height fields have become an important element of realistic real-time image
      synthesis to represent surface details. In this paper, we focus on the frequent
      case of static height-field data, for which we can precompute acceleration
      structures. While many rendering algorithms exist that impose tradeoffs between
      speed and accuracy, we show that even accurate rendering can be combined with
      high performance. A careful analysis of the surface defined by the height values,
      leads to an efficient and accurate precomputation method. As a result, each texel
      stores a safety shape inside which a ray cannot cross the surface twice. This
      property ensures that no intersections are missed during the efficient marching
      method. Our analysis is general and can even consider visibility constraints that
      are robustly integrated into the precomputation. Further, we propose a particular
      instance of safety shapes with little memory overhead, which results in a
      rendering algorithm that outperforms existing methods, both in terms of accuracy
      and performance. 

PMID- 22144531
TI  - Stochastic gene expression modeling with Hill function for switch-like gene
      responses.
AB  - Gene expression models play a key role to understand the mechanisms of gene
      regulation whose aspects are grade and switch-like responses. Though many
      stochastic approaches attempt to explain the gene expression mechanisms, the
      Gillespie algorithm which is commonly used to simulate the stochastic models
      requires additional gene cascade to explain the switch-like behaviors of gene
      responses. In this study, we propose a stochastic gene expression model
      describing the switch-like behaviors of a gene by employing Hill functions to the
      conventional Gillespie algorithm. We assume eight processes of gene expression
      and their biologically appropriate reaction rates are estimated based on
      published literatures. We observed that the state of the system of the toggled
      switch model is rarely changed since the Hill function prevents the activation of
      involved proteins when their concentrations stay below a criterion. In ScbA-ScbR
      system, which can control the antibiotic metabolite production of microorganisms,
      our modified Gillespie algorithm successfully describes the switch-like behaviors
      of gene responses and oscillatory expressions which are consistent with the
      published experimental study.

PMID- 22144533
TI  - Metagenomic analysis of brain abscesses identifies specific bacterial
      associations.
AB  - BACKGROUND: The bacterial flora involved in brain abscess is often complex. In a
      previous study, using a metagenomic approach based on 16S ribosomal DNA (rDNA)
      amplification, we demonstrated that the diversity of the microbial flora involved
      in these infections was underestimated. METHODS: We performed a 16S rDNA-based
      metagenomic analysis of cerebral abscesses from patients diagnosed from 2006
      through 2010. All bacteria present in brain abscess specimens were identified, in
      view of the clinical and epidemiological characteristics of the patients.
      RESULTS: Fifty-one patients were included in our study. By detecting
      polymicrobial infections in 19 patients, our strategy was significantly more
      discriminatory and enabled the identification of a greater number of bacterial
      taxa than did culture and conventional 16S rDNA polymerase chain reaction (PCR)
      and sequencing, respectively (P < 10(-2)). Data mining discriminated 2 distinct
      bacterial populations in brain abscess from dental and sinusal origin. In
      addition, of the 80 detected bacterial species, we identified 44 bacteria that
      had never been found in brain abscess specimens, including 22 uncultured
      bacteria. These uncultured agents mostly originated from the buccal or sinusal
      floras (P < 10(-2)) and were found in polymicrobial specimens (P < 10(-2)).
      CONCLUSIONS: Cloning and sequencing of PCR-amplified 16S rDNA is a highly
      valuable method to identify bacterial agents of brain abscesses.

PMID- 22144534
TI  - Global TravEpiNet: a national consortium of clinics providing care to
      international travelers--analysis of demographic characteristics, travel
      destinations, and pretravel healthcare of high-risk US international travelers,
      2009-2011.
AB  - BACKGROUND:  International travel poses a risk of destination-specific illness
      and may contribute to the global spread of infectious diseases. Despite this,
      little is known about the health characteristics and pretravel healthcare of US
      international travelers, particularly those at higher risk of travel-associated
      illness. METHODS:  We formed a national consortium (Global TravEpiNet) of 18 US
      clinics registered to administer yellow fever vaccination. We collected data
      regarding demographic and health characteristics, destinations, purpose of
      travel, and pretravel healthcare from 13235 international travelers who sought
      pretravel consultation at these sites from January 2009 through January 2011.
      RESULTS:  The destinations and itineraries of Global TravEpiNet travelers
      differed from those of the overall population of US international travelers. The
      majority of Global TravEpiNet travelers were visiting low- or lower-middle-income
      countries, and Africa was the most frequently visited region. Seventy-five
      percent of travelers were visiting malaria-endemic countries, and 38% were
      visiting countries endemic for yellow fever. Fifty-nine percent of travelers
      reported >=1 medical condition. Atovaquone/proguanil was the most commonly
      prescribed antimalarial drug, and most travelers received an antibiotic for self
      treatment of travelers' diarrhea. Hepatitis A and typhoid were the most
      frequently administered vaccines. CONCLUSIONS:  Data from Global TravEpiNet
      provide insight into the characteristics and pretravel healthcare of US
      international travelers who are at increased risk of travel-associated illness
      due to itinerary, purpose of travel, or existing medical conditions. Improved
      understanding of this epidemiologically significant population may help target
      risk-reduction strategies and interventions to limit the spread of infections
      related to global travel.

PMID- 22144535
TI  - Cytokine gene polymorphisms and the outcome of invasive candidiasis: a
      prospective cohort study.
AB  - BACKGROUND:  Candida bloodstream infections cause significant morbidity and
      mortality among hospitalized patients. Although clinical and microbiological
      factors affecting prognosis have been identified, the impact of genetic variation
      in the innate immune responses mediated by cytokines on outcomes of infection
      remains to be studied. METHODS:  A cohort of 338 candidemia patients and 351
      noninfected controls were genotyped for single-nucleotide polymorphisms (SNPs) in
      6 cytokine genes (IFNG, IL10, IL12B, IL18, IL1beta, IL8) and 1 cytokine receptor
      gene (IL12RB1). The association of SNPs with both candidemia susceptibility and
      outcome were assessed. Concentrations of pro- and antiinflammatory cytokines were
      measured in in vitro peripheral blood mononuclear cell stimulation assays and in
      serum from infected patients. RESULTS:  None of the cytokine SNPs studied were
      associated with susceptibility to candidemia. Persistent fungemia occurred in 13%
      of cases. In the multivariable model, persistent candidemia was significantly
      associated with (odds ratio [95% confidence interval]): total parenteral
      nutrition (2.79 [1.26-6.17]), dialysis dependence (3.76 [1.46-8.64]), and the
      SNPs IL10 rs1800896 (3.45 [1.33-8.93]) and IL12B rs41292470 (5.36 [1.51-19.0]).
      In vitro production capacity of interleukin-10 and interferon-gamma was
      influenced by these polymorphisms, and significantly lower proinflammatory
      cytokine concentrations were measured in serum from patients with persistent
      fungemia. CONCLUSIONS:  Polymorphisms in IL10 and IL12B that result in low
      production of proinflammatory cytokines are associated with persistent fungemia
      in candidemia patients. This provides insights for future targeted management
      strategies for patients with Candida bloodstream infections.

PMID- 22144536
TI  - A retrospective comparison of ceftriaxone versus oxacillin for osteoarticular
      infections due to methicillin-susceptible Staphylococcus aureus.
AB  - BACKGROUND: Antistaphylococcal penicillins are the treatment of choice for
      methicillin-susceptible Staphylococcus aureus (MSSA) infection. Ceftriaxone can
      be dosed once daily and is less expensive for outpatient therapy than oxacillin.
      We compared patient outcomes of MSSA osteoarticular infections treated with
      ceftriaxone versus oxacillin. METHODS: We conducted a retrospective cohort study
      of patients with MSSA osteoarticular infections at a tertiary care hospital from
      January 2005 to April 2010. We collected demographic, clinical, and outcome data
      including treatment-related adverse events. Successful treatment (clinical
      improvement; improved follow-up markers and imaging; no readmission for
      treatment) was compared at 3-6 months and >6 months after completion of
      intravenous antibiotics. RESULTS: In total, 124 patients had an MSSA
      osteoarticular infection; 64 (52%) had orthopedic hardware involvement. Of those
      patients, 74 (60%) received ceftriaxone and 50 (40%) received oxacillin.
      Oxacillin was more often discontinued due to toxicity (9 of 50 [18%] oxacillin vs
      3 of 74 [4%] ceftriaxone; P = .01). At 3-6 and >6 months, data for 97 and 88
      patients, respectively, were available for analysis. Treatment success was
      similar at 3-6 months (50 of 60 [83%] ceftriaxone vs 32 of 37 [86%] oxacillin; P
      = .7) and >6 months (43 of 56 [77%] ceftriaxone vs 26 of 32 [81%] oxacillin; P =
      .6). After intravenous antibiotics, 56 (45%) patients received long-term
      suppression with oral antibiotics (31 of 74 [42%] ceftriaxone vs 25 of 50 [50%]
      oxacillin; P = .4). CONCLUSIONS: In this comparison of ceftriaxone versus
      oxacillin for MSSA osteoarticular infections, there was no difference in
      treatment success at 3-6 and >6 months following the completion of intravenous
      antibiotics. Patients receiving oxacillin were more likely to have it
      discontinued due to toxicity.

PMID- 22144538
TI  - Consensus statement on diagnostic end points for infant tuberculosis vaccine
      trials.
AB  - BACKGROUND:  Definition of clinical trial end points for childhood tuberculosis
      is hindered by lack of a standard case definition. We aimed to identify areas of
      consensus or debate on potential end points for tuberculosis vaccine trials among
      human immunodeficiency virus-uninfected children. METHODS:  Thirty-eight opinion
      leaders participated in a Consensus Workshop at the Second Global Forum on TB
      Vaccines (Estonia, 2010). Outcomes were categorized as unanimity, modified
      consensus, or lack of consensus. Individual reservations were noted. RESULTS: 
      Modified consensus was achieved on 3 issues: (1) unsuitability of historical BCG
      trial end points as sole primary end points for modern infant trials; (2)
      symptomatic, complicated intrathoracic tuberculosis as an uncommon but clinically
      relevant disease phenotype; (3) primary complex tuberculosis in younger children
      as a common, high-risk phenotype, with a high rate of spontaneous resolution.
      Participants agreed that radiologic diagnosis of intrathoracic tuberculosis would
      be based primarily on hilar lymphadenopathy. Lack of consensus was noted for (1)
      significance of isolated culture of Mycobacterium tuberculosis and (2) the need
      for evidence of prior tuberculosis exposure to support a diagnosis of
      tuberculosis disease. Reservations were expressed regarding use of interferon
      gamma release assays and the clinical relevance, and potential for
      misclassification, of primary complex tuberculosis. CONCLUSIONS:  The Workshop
      did not achieve consensus on a single primary end-point definition. Tuberculosis
      disease phenotypes with optimal diagnostic certainty will be uncommon in the
      study population. Criteria for composite or multiple end points were identified,
      and we propose a hierarchy of end-point criteria, based on rate of occurrence,
      clinical relevance, and diagnostic certainty.

PMID- 22144540
TI  - Hemorrhagic fever caused by a novel Bunyavirus in China: pathogenesis and
      correlates of fatal outcome.
AB  - BACKGROUND:  Hemorrhagic fever-like illness caused by a novel Bunyavirus,
      Huaiyangshan virus (HYSV, also known as Severe Fever with Thrombocytopenia virus
      [SFTSV] and Fever, Thrombocytopenia and Leukopenia Syndrome [FTLS]), has recently
      been described in China. METHODS:  Patients with laboratory-confirmed HYSV
      infection who were admitted to Union Hospital or Zhongnan Hospital between April
      2010 and October 2010 were included in this study. Clinical and routine
      laboratory data were collected and blood, throat swab, urine, or feces were
      obtained when possible. Viral RNA was quantified by real-time reverse
      transcriptase polymerase chain reaction. Blood levels of a range of cytokines,
      chemokines, and acute phase proteins were assayed. RESULTS:  A total of 49
      patients with hemorrhagic fever caused by HYSV were included; 8 (16.3%) patients
      died. A fatal outcome was associated with high viral RNA load in blood at
      admission, as well as higher serum liver transaminase levels, more pronounced
      coagulation disturbances (activated partial thromboplastin time, thrombin time),
      and higher levels of acute phase proteins (phospholipase A, fibrinogen,
      hepcidin), cytokines (interleukin [IL]-6, IL-10, interferon-gamma), and
      chemokines (IL-8, monocyte chemotactic protein 1, macrophage inflammatory protein
      1b). The levels of these host parameters correlated with viral RNA levels. Blood
      viral RNA levels gradually declined over 3-4 weeks after illness onset,
      accompanied by resolution of symptoms and laboratory abnormalities. Viral RNA was
      also detectable in throat, urine, and fecal specimens of a substantial proportion
      of patients, including all fatal cases assayed. CONCLUSIONS. Viral replication
      and host immune responses play an important role in determining the severity and
      clinical outcome in patients with infection by HYSV.

PMID- 22144541
TI  - Hyperprocalcitonemia due to mushroom poisoning.

PMID- 22144539
TI  - A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV
      infected pregnant women receiving a single intrapartum dose of nevirapine.
AB  - BACKGROUND: Intrapartum single-dose (SD) nevirapine (NVP) reduces perinatal
      transmission of human immunodeficiency virus (HIV) infection but selects for NVP
      resistant virus, which compromises subsequent NVP-based therapy. A 1-week "tail"
      of lamivudine and zidovudine after SD-NVP decreases the risk of resistance. We
      hypothesized that increasing the duration or potency of the tail would further
      reduce this risk to <10%, using a sensitive assay to measure resistance. METHODS:
      HIV-infected pregnant Thai women with a CD4 cell count >250 cells/MUL, most
      receiving zidovudine, were randomized at 28-38 weeks gestation to receive 1 of 3
      intrapartum and postpartum regimens: (A) zidovudine plus enteric-coated
      didanosine plus lopinavir and ritonavir for 7 days, (B) zidovudine plus enteric
      coated didanosine for 30 days, or (C) regimen 1 for 30 days. The incidence of NVP
      resistance mutations at day 10 or week 6 post partum in each arm was compared
      with that of a historical comparison group who received prenatal zidovudine and
      SD-NVP. NVP resistance was identified by consensus sequencing and a sensitive
      oligonucleotide ligation assay (OLA). RESULTS: At entry, the 169 participants had
      a median CD4 cell count of 456 cells/MUL and an HIV load of 3.49 log(10)
      copies/mL. The incidence of mutations in each of the 3 P1032 arms was 0% by
      sequencing and 1.8%, 7.1%, and 5.3% by OLA in arms A, B, and C, respectively,
      compared with 13.4% by sequencing and 29.4% by OLA in the comparison group (P <
      .001 for each study arm vs comparison group). Grade 4 anemia developed in 1
      woman. CONCLUSIONS: A 7-day tail of highly active combination therapy or 1 month
      of dual therapy after SD-NVP prevents most NVP resistance to minimal toxicity.
      CLINICAL TRIALS REGISTRATION: The IMPAACT P1032 Clinical Trial is NCT00109590,
      and the PHPT-2 Clinical Trial is NCT00398684.

PMID- 22144542
TI  - Infection with multiple avian influenza viruses in a man without poultry-handling
      practices suggesting an increased probability of emergent pandemic influenza
      virus in general population.

PMID- 22144537
TI  - Outcomes following candiduria in extremely low birth weight infants.
AB  - BACKGROUND: Candidiasis carries a significant risk of death or neurodevelopmental
      impairment (NDI) in extremely low birth weight infants (ELBW; <1000 g). We sought
      to determine the impact of candiduria in ELBW preterm infants. METHODS: Our study
      was a secondary analysis of the Neonatal Research Network study Early Diagnosis
      of Nosocomial Candidiasis. Follow-up assessments included Bayley Scales of Infant
      Development examinations at 18-22 months of corrected age. Risk factors were
      compared between groups using exact tests and general linear modeling. Death,
      NDI, and death or NDI were compared using generalized linear mixed modeling.
      RESULTS: Of 1515 infants enrolled, 34 (2.2%) had candiduria only. Candida was
      isolated from blood only (69 of 1515 [4.6%]), cerebrospinal fluid (CSF) only (2
      of 1515 [0.1%]), other sterile site only (not urine, blood, or CSF; 4 of 1515
      [0.3%]), or multiple sources (28 of 1515 [2%]). Eleven infants had the same
      Candida species isolated in blood and urine within 3 days; 3 (27%) had a positive
      urine culture result first. Most urine isolates were Candida albicans (21 of 34
      [62%]) or Candida parapsilosis (7 of 34 [29%]). Rate of death or NDI was greater
      among those with candiduria (50%) than among those with suspected but not proven
      infection (32%; odds ratio, 2.5 [95% confidence interval, 1.2-5.3]) after
      adjustment. No difference in death and death or NDI was noted between infants
      with candiduria and those with candidemia. CONCLUSIONS: These findings provide
      compelling evidence that ELBW infants with candiduria are at substantial risk of
      death or NDI. Candiduria in ELBW preterm infants should prompt a systemic
      evaluation (blood, CSF, and abdominal ultrasound) for disseminated Candida
      infection and warrants treatment.

PMID- 22144544
TI  - HIV-1 subtype and virological response to antiretroviral therapy: acquired drug
      resistance.

PMID- 22144545
TI  - Botulism toxemia following laparoscopic appendectomy.
AB  - We describe a case of botulism infection in a patient who had undergone
      laparoscopic appendectomy, an occurrence not previously described in the
      literature. This case exemplifies the need for coordination between clinical and
      public health personnel to ensure the immediate recognition and treatment of
      suspected botulism cases.

PMID- 22144546
TI  - Use of procalcitonin to guide duration of antimicrobial therapy in intensive care
      units: proceed with caution.

PMID- 22144548
TI  - Nuclear medicine at a crossroads.
AB  - The growth of molecular imaging heightens the promise of clinical nuclear
      medicine as a tool for individualization of patient care and for improvement of
      health-care outcomes. Together with greater use of integrated structure-function
      imaging, clinical nuclear medicine reaches beyond traditional specialty borders
      into diagnostic radiology and oncology. Yet, there are concerns about the future
      of nuclear medicine, including progressively declining reimbursement, the
      competitive advantages of diagnostic radiology, limited translation of research
      accomplishments to clinical diagnostic imaging and patient care, and an
      insufficient pool of incoming highly qualified nuclear medicine clinicians. Thus,
      nuclear medicine views itself as being at a critical crossroads. What will be
      important is for nuclear medicine to be positioned as the quintessential
      molecular imaging modality more centrally within medical imaging and for the
      integration of nuclear medicine with primary care specialties to be driven more
      by patient needs than by specialty needs. In this way, the full potential of
      nuclear medicine as an effective and efficient tool for improving patient
      outcomes can be realized.

PMID- 22144547
TI  - Long-term outcomes in hypertrophic cardiomyopathy caused by mutations in the
      cardiac troponin T gene.
AB  - BACKGROUND: Hypertrophic cardiomyopathy caused by mutations in the cardiac
      troponin T gene (TNNT2) has been associated with a high risk of sudden cardiac
      death (SCD) and mild left ventricular hypertrophy. However, previous studies are
      limited by sample size, cross-sectional design, and few data in relatives.
      METHODS AND RESULTS: Five hundred fifty-two unrelated hypertrophic cardiomyopathy
      probands were screened for TNNT2 mutations. First-degree relatives were invited
      for clinical and genetic evaluation. Ninety-two individuals (20 probands and 72
      relatives) carried TNNT2 mutations (51 [55%] male; 30+/-17 years). ECGs and echo
      were available in 87 (95%) and 88 (96%) individuals, respectively. ECG was normal
      in 13 (68%) children (<16 years) and 13 (19%) adults. Echo was normal in 18 (90%)
      children and 16 (24%) adults; 7 (10%) adults had a normal ECG and echo. Thirteen
      (65%) of 20 families had a history of SCD. Follow-up was available for 75
      patients (mean, 9.9+/-5.2 years); 2 of 16 adults and 2 of 18 children with normal
      echoes developed left ventricular hypertrophy. Twenty-three (22%) received an
      implantable cardioverter-defibrillator (20 for primary prophylaxis). One child
      and 3 adults died of SCD and 2 adults were resuscitated from ventricular
      fibrillation. One patient had an appropriate implantable cardioverter
      defibrillator discharge. The rate of cardiovascular death, transplant, and
      implantable cardioverter-defibrillator discharge was 1.6% (0.016 person/y; 95%
      confidence interval, 0.83-2.79%), and SCD 0.93% (0.0093 person/y; 95% confidence
      interval, 0.37-1.92%). CONCLUSIONS: Left ventricular hypertrophy is rare in
      children with TNNT2 mutations. Left ventricular hypertrophy is absent in the
      minority of adults, but most have an abnormal ECG. Despite adverse family
      histories, the rate of cardiovascular death during follow-up was similar to that
      reported in large referral populations.

PMID- 22144549
TI  - Trends in nuclear medicine in developing countries.
AB  - This article describes trends in nuclear medicine in the developing world as
      noted by nuclear medicine professionals at the International Atomic Energy Agency
      (IAEA). The trends identified are based on data gathered from several sources,
      including information gathered through a database maintained by the IAEA;
      evaluation of country program frameworks of various IAEA Member States; personal
      interactions with representatives in the nuclear medicine field from different
      regions of the world; official proceedings and meeting reports of the IAEA;
      participation in numerous national, regional, and international conferences;
      discussions with the leadership of major professional societies; and relevant
      literature. The information presented in this article relied on both objective
      and subjective observations. The aims of this article were to reflect on recent
      developments in the specialty of nuclear medicine and to envision the directions
      in which it is progressing. These issues are examined in terms of dimensions of
      practice, growth, and educational and training needs in the field of nuclear
      medicine. This article will enable readers to gain perspective on the status of
      nuclear medicine practice, with a specific focus on the developing world, and to
      examine needs and trends arising from the observations.

PMID- 22144550
TI  - Issues and controversies in nuclear medicine. Introduction.

PMID- 22144551
TI  - Status of and trends in nuclear medicine in the United States.
AB  - Nuclear medicine in the United States has grown because of advances in
      technology, including hybrid imaging, the introduction of new
      radiopharmaceuticals for diagnosis and therapy, and the development of molecular
      imaging based on the tracer principle, which is not based on radioisotopes.
      Continued growth of the field will require cost-effectiveness data and evidence
      that nuclear medicine procedures affect patients' outcomes. Nuclear medicine
      physicians and radiologists will need more training in anatomic and molecular
      imaging. New educational models are being developed to ensure that future
      physicians will be adequately prepared.

PMID- 22144552
TI  - Subjective perception of radiation risk.
AB  - Physicians, medical staff, and patients, much like the general population, are
      becoming increasingly sensitized to the issue of radiation exposure from
      diagnostic or therapeutic procedures. The attitudes of patients undergoing
      diagnostic imaging procedures that use ionizing radiation vary widely. Patient
      perception of radiation dose strongly influences their acceptance of diagnostic
      examinations or therapies involving radioactivity. Here, we review perceptions
      and concerns about radiation and radioactivity by laypersons and medical experts.
      Several studies show that physicians are frequently poorly informed about
      radiation levels associated with nuclear medicine and radiologic examinations. In
      addition, patients' decisions against undergoing an imaging procedure are
      frequently based on partial and sometimes incorrect information. Thus, physicians
      must take the concerns of their patients seriously. From the literature and our
      own experience, we conclude that it is extremely important to thoroughly and
      carefully educate all involved in patient work-up about radiation exposure levels
      and perceived or actual health risks. Although the choice and timing of imaging
      examinations should always outweigh the risk that secondary illness will develop,
      the patients' concerns still must be alleviated.

PMID- 22144553
TI  - How many PET tracers do we need?
AB  - The recognized need for new PET tracers is associated with increases in available
      PET instrumentation and with unmet clinical challenges in the early diagnosis and
      staging of diseases. The clinical success of (18)F-FDG PET has resulted in the
      acceptance of biologic signals as part of disease management. The advantages of
      PET technology over SPECT will lead to the introduction of new PET tracers for
      established nuclear medicine imaging indications. Disease-specific markers such
      as amyloid ligands will lead to new applications of PET to neurodegenerative
      diseases that are prevalent in aging societies. The translation of molecular
      imaging to clinical applications will require combining specific tracer
      approaches with targeted therapy for the realization of personalized medicine. An
      important aspect of the introduction of new PET tracers will be the emergence of
      a specialized radiopharmaceutical industry and professional distribution
      networks. The number of available PET tracers not only will follow rules of
      demand and supply but also will be dependent on the regulatory environment of
      individual health care systems.

PMID- 22144554
TI  - The Janus project: the remaking of nuclear medicine and radiology.

PMID- 22144555
TI  - Radiopeptide imaging and therapy in Europe.
AB  - Receptor targeting with radiolabeled peptides has become an important topic,
      particularly in nuclear oncology. Strong research efforts are under way in
      radiopharmaceutical science laboratories and in nuclear medicine departments in
      Europe. The target receptors belong to the large family of G-protein-coupled
      receptors. The prototypes of these radiopeptides are based on analogs of
      somatostatin targeting somatostatin receptor-positive tumors, particularly well
      differentiated neuroendocrine tumors. These radiopeptides have an important
      impact not only on diagnosis but also on targeted radionuclide therapy of these
      tumors. Besides the registered radiopeptide (111)In-pentetreotide, efficient
      SPECT tracers labeled with (99m)Tc and PET agents based on generator-produced
      (68)Ga have been developed and used in the clinic. In parallel to the development
      of diagnostic agents, radiopeptides labeled with the beta(-) emitters (90)Y and
      (177)Lu are also widely used. Because the same chelators and therefore the same
      conjugates can be used in diagnosis and therapy, they constitute ideal
      theranostic pairs. This progress is driven not only by scientists and clinicians
      but also by patient interest groups. New radiopeptides targeting other G-protein
      coupled receptors are entering the clinic, among them glucagon-like peptide 1
      receptor-targeting molecules. This receptor is overexpressed on literally all
      benign insulinomas. (111)In-labeled derivatives of the insulinotropic 39-mer
      peptide exendin-4 were beneficial in the pre- and perioperative localization of
      these benign lesions. In contrast, lack of localization may indicate malignant
      insulinoma. The bombesin- and gastrin-releasing peptide receptor family is
      potentially important because these receptors are overexpressed on major human
      tumors such as prostate tumors, breast tumors, gastrointestinal stromal tumors,
      and vessels of ovarian cancer. (99m)Tc-labeled peptides for SPECT and (68)Ga-, as
      well as (64)Cu-labeled agonists or antagonists, have been studied in breast
      tumors, prostate tumors, gastrointestinal stromal tumors, and gliomas with
      considerable success. A phase I therapeutic study with a (177)Lu-labeled agonist
      has been completed. There are not enough clinical data available to reveal the
      significance of these new modalities in patient care, but several phase I studies
      are under way in larger patient cohorts using PET agents. Another G-protein
      coupled receptor with high overexpression on human tumors is the
      gastrin/cholecystokinin-2 receptor. It is overexpressed in more than 90% of cases
      of medullary thyroid cancer, in small cell lung cancer, and in a subgroup of
      neuroendocrine tumors. Correlating with in vitro receptor localization using
      autoradiography of 27 patients with metastasized medullary thyroid cancer, SPECT
      or planar imaging of these patients resulted in a 95% sensitivity of tumor
      localization. Finally, another G-protein-coupled receptor is found in brain
      tumors and peritumoral vessels. Literally all cases of glioblastoma multiforme
      overexpress the neurokinin type 1 receptor; the natural ligand is substance P,
      which was metabolically stabilized, labeled with (90)Y and (213)Bi, and injected
      into resection cavities or directly into tumors, which were critically located
      via a catheter system. The major advantage of this approach appeared to be the
      facilitated resectability of tumors, particularly in those patients who had been
      treated up front with the locoregional approach. It appears that neoadjuvant
      treatment before resection is a valid concept. Finally, another peptide family,
      the arginine-glycine-aspartate-based radiotracers, has made it to the clinic
      labeled with a variety of radioisotopes for monitoring the integrins
      alpha(v)beta(3) overexpressed during tumor angiogenesis.

PMID- 22144556
TI  - Radiopeptide imaging and therapy in the United States.
AB  - Radiolabeled peptides targeted against receptors on the cell surface have been
      shown to be remarkably specific and effective in the diagnosis and therapy of
      malignant disease. Much of the early work in this field took place outside the
      United States, but in recent years the research effort within the United States
      has accelerated. Most of the initial studies in the United States focused on
      somatostatin receptor ligands. (111)In-pentetreotide was approved in 1994 and has
      been used extensively in the diagnosis and management of a wide variety of
      neuroendocrine tumors, particularly carcinoid. This work was extended to (99m)Tc
      labeled analogs, and the most successful, (99m)Tc-depreotide, was approved in
      1999. This agent was found to be accurate in the diagnosis of lung cancer, but it
      was not particularly successful because it was supplanted by (18)F-FDG imaging
      with positron tomography. More recently, studies with (68)Ga-labeled somatostatin
      analogs were initiated in the United States. This effort was delayed relative to
      that in other parts of the world because of difficulty in obtaining the necessary
      generators and regulatory uncertainty, both of which are less of a problem
      currently. Several ligands are being developed to image melanoma through
      targeting of the melanocyte-stimulating hormone receptor. Other ligands are being
      developed to use the arginine-glycine-aspartate oligopeptide to target
      angiogenesis and to use bombesin analogs to target the gastrin-releasing peptide
      receptor for the diagnosis and potential therapy of prostate cancer. Peptide
      dimers that target 2 receptors simultaneously are also being constructed,
      potentially increasing the selectivity of the approach significantly.
      Radiopeptide therapy has been explored with these ligands, initially with high
      dose (111)In-pentetreotide. This step has been followed by U.S. participation in
      several trials with (90)Y-, (177)Lu-, and (188)Re-labeled analogs. Some of these
      agents are now available clinically outside the United States, and it is
      important to design and conduct the appropriate trials so that this therapy can
      be offered within the United States.

PMID- 22144557
TI  - Doing more harm than good? Do systematic reviews of PET by health technology
      assessment agencies provide an appraisal of the evidence that is closer to the
      truth than the primary data supporting its use?
AB  - Health technology assessment (HTA) has the objective of providing individual
      patients, clinicians, and funding bodies with the highest-quality information on
      the net patient benefits and cost effectiveness of medical interventions. Founded
      on systematic reviews of the available evidence, HTA aims to reduce bias and
      thereby provide a more valid evaluation of the benefits of new medical
      interventions than the primary studies themselves. Competing with the traditional
      role of medical experts, HTA agencies have gained considerable influence over
      public opinion and policy. The fundamental tenets of evidence-based medicine
      mandate that this influence should be used first and foremost for the benefit of
      patients. Over nearly 2 decades, multiple HTA systematic reviews in many
      countries have discredited most or all of the evidence pertaining to the ability
      of PET to improve patient-important outcomes. These determinations have delayed,
      restricted, and, in many cases, prevented access to this technology, especially
      by cancer patients. HTA systematic review findings are very much at variance with
      the opinion of clinicians. Our scrutiny of these reviews, benchmarking them
      against the core values of science and evidence-based medicine, has revealed
      errors of fact, inappropriate exclusion of pertinent data, and injudicious
      appraisal of the clinical relevance of evidence, potentially introducing bias
      into these reviews and compromising the validity of their conclusions about the
      net patient benefits of PET. We believe that our findings mandate that the
      molecular imaging community actively engage institutionalized HTA agencies to
      ensure appropriate representation of our primary data and adherence to the
      highest principles of evidence-based medicine.

PMID- 22144558
TI  - Is there evidence for evidence-based medical imaging?

PMID- 22144559
TI  - Generating evidence for clinical benefit of PET/CT in diagnosing cancer patients.
AB  - For diagnostic methods such as PET/CT, not only diagnostic accuracy but also
      clinical benefit must be demonstrated. However, there is a lack of consensus
      about how to approach this task. Here we consider 6 clinical scenarios to review
      some basic approaches to demonstrating the clinical benefit of PET/CT in cancer
      patients: replacement of an invasive procedure, improved accuracy of initial
      diagnosis, improved accuracy of staging for curative versus palliative treatment,
      improved accuracy of staging for radiation versus chemotherapy, response
      evaluation, and acceleration of clinical decisions. We also develop some
      guidelines for the evaluation of clinical benefit. First, it should be clarified
      whether there is a direct benefit of the use of PET/CT or an indirect benefit
      because of improved diagnostic accuracy. If there is an indirect benefit, then
      decision modeling should be used initially to assess the benefit expected from
      the use of PET/CT. Only if decision modeling does not allow definitive
      conclusions should randomized controlled trials be planned.

PMID- 22144560
TI  - Contribution of imaging to cancer care costs.
AB  - Health care costs in the United States are increasing faster than the gross
      domestic product (GDP), and the growth rate of costs related to diagnostic
      imaging exceeds those of overall health care expenditures. Here we show that the
      contribution of imaging to cancer care costs pales in comparison to those of
      other key cost components, such as cancer drugs. Specifically, we estimate that
      (18)F-FDG PET or PET/CT accounted for approximately 1.5% of overall Medicare
      cancer care costs in 2009. Moreover, we propose that the appropriate use of (18)F
      FDG PET or PET/CT could reduce the costs of cancer care. Because the U.S. health
      care system is complex and because it is difficult to find accurate data
      elsewhere, most cost and use assessments are based on published data from the
      U.S. Centers for Medicare & Medicaid Services.

PMID- 22144561
TI  - Need for standardization of 18F-FDG PET/CT for treatment response assessments.
AB  - Many factors affect standardized uptake values (SUVs) in (18)F-FDG PET/CT. The
      use of the SUV from a single PET scan in multicenter studies requires the
      standardization of (18)F-FDG PET/CT procedures. In the context of treatment
      response assessments (repeated PET scans), many factors may seem to have minor
      effects on percentage changes in SUVs, provided that imaging procedures are
      executed in a consistent manner for each subject. However, the use of (18)F-FDG
      PET/CT in a nonstandardized manner will result in unknown biases and
      reproducibilities of SUVs and SUV-based response measures. This article provides
      an overview of the need for standardization in relation to the specific use of
      SUVs and SUV changes in studies of treatment response assessments.

PMID- 22144562
TI  - Task-irrelevant perceptual expertise.
AB  - Perceptual learning (PL) and perceptual expertise (PE) are two fields of visual
      training studies that investigate how practice improves visual performance.
      However, previous research suggests that PL can be acquired in a task-irrelevant
      manner while PE cannot and that PL is highly specific to the training objects and
      conditions while PE generalizes. These differences are difficult to interpret
      since PL and PE studies tend to differ on multiple dimensions. We designed a
      training study with novel objects to compare PL and PE while varying only the
      training task, such that the training objects, visual field, training duration,
      and type of learning assessment were kept constant. Manipulations of the training
      task sufficed to produce the standard effects obtained in PE and PL. In contrast
      to prior studies, we demonstrated that some degree of PE can be acquired in a
      task-irrelevant manner, similar to PL. Task-irrelevant PE resulted in similar
      shape matching ability compared to the directly trained PE. In addition, learning
      in both PE and PL generalizes to different untrained conditions, which does not
      support the idea that PE generalizes while PL is specific. Degrees of
      generalization can be explained by considering the psychological space of the
      stimuli used for training and the test of transfer.

PMID- 22144564
TI  - Advancement of motion psychophysics: review 2001-2010.
AB  - This is a survey of psychophysical studies of motion perception carried out
      mainly in the last 10 years. It covers a wide range of topics, including the
      detection and interactions of local motion signals, motion integration across
      various dimensions for vector computation and global motion perception, second
      order motion and feature tracking, motion aftereffects, motion-induced
      mislocalizations, timing of motion processing, cross-attribute interactions for
      object motion, motion-induced blindness, and biological motion. While traditional
      motion research has benefited from the notion of the independent "motion
      processing module," recent research efforts have been also directed to aspects of
      motion processing in which interactions with other visual attributes play
      critical roles. This review tries to highlight the richness and diversity of this
      large research field and to clarify what has been done and what questions have
      been left unanswered.

PMID- 22144563
TI  - Decoding simulated neurodynamics predicts the perceptual consequences of age
      related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the major cause of blindness in the
      developed world. Though substantial work has been done to characterize the
      disease, it is difficult to predict how the state of an individual's retina will
      ultimately affect their high-level perceptual function. In this paper, we
      describe an approach that couples retinal imaging with computational neural
      modeling of early visual processing to generate quantitative predictions of an
      individual's visual perception. Using a patient population with mild to moderate
      AMD, we show that we are able to accurately predict subject-specific psychometric
      performance by decoding simulated neurodynamics that are a function of scotomas
      derived from an individual's fundus image. On the population level, we find that
      our approach maps the disease on the retina to a representation that is a
      substantially better predictor of high-level perceptual performance than
      traditional clinical metrics such as drusen density and coverage. In summary, our
      work identifies possible new metrics for evaluating the efficacy of treatments
      for AMD at the level of the expected changes in high-level visual perception and,
      in general, typifies how computational neural models can be used as a framework
      to characterize the perceptual consequences of early visual pathologies.

PMID- 22144565
TI  - Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats.
AB  - Antipsychotics are an important class of drugs for the management of
      schizophrenia and other psychotic disorders. They act by blocking dopamine
      receptors; however, because these receptors are present throughout the brain,
      prolonged antipsychotic use also leads to serious side effects. These include
      tardive dyskinesia, repetitive abnormal involuntary movements of the face and
      limbs for which there is little treatment. In this study, we investigated whether
      nicotine administration could reduce tardive dyskinesia because nicotine
      attenuates other drug-induced abnormal movements. We used a well established
      model of tardive dyskinesia in which rats injected with the commonly used
      antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble
      human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2
      mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once
      daily. Nicotine treatment reduced haloperidol-induced VCMs by ~20% after 5 weeks,
      with a significant ~60% decline after 13 weeks. There was no worsening of
      haloperidol-induced catalepsy. To understand the molecular basis for this
      improvement, we measured the striatal dopamine transporter and nicotinic
      acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment
      decreased the transporter and alpha6beta2* nAChRs (the asterisk indicates the
      possible presence of other nicotinic subunits in the receptor complex) when given
      alone, with no further decline with combined drug treatment. By contrast,
      nicotine alone increased, while haloperidol reduced alpha4beta2* nAChRs in both
      vehicle and haloperidol-treated rats. These data suggest that molecular
      mechanisms other than those directly linked to the transporter and nAChRs
      underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats.
      The present results are the first to suggest that nicotine may be useful for
      improving the tardive dyskinesia associated with antipsychotic use.

PMID- 22144566
TI  - Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate
      atherosclerotic lesions.
AB  - BACKGROUND: Atherosclerotic lesions are believed to grow via the recruitment of
      bone marrow-derived monocytes. Among the known murine monocyte subsets, Ly
      6C(high) monocytes are inflammatory, accumulate in lesions preferentially, and
      differentiate. Here, we hypothesized that the bone marrow outsources the
      production of Ly-6C(high) monocytes during atherosclerosis. METHODS AND RESULTS:
      Using murine models of atherosclerosis and fate-mapping approaches, we show that
      hematopoietic stem and progenitor cells progressively relocate from the bone
      marrow to the splenic red pulp, where they encounter granulocyte macrophage
      colony-stimulating factor and interleukin-3, clonally expand, and differentiate
      to Ly-6C(high) monocytes. Monocytes born in such extramedullary niches
      intravasate, circulate, and accumulate abundantly in atheromata. On lesional
      infiltration, Ly-6C(high) monocytes secrete inflammatory cytokines, reactive
      oxygen species, and proteases. Eventually, they ingest lipids and become foam
      cells. CONCLUSIONS: Our findings indicate that extramedullary sites supplement
      the hematopoietic function of the bone marrow by producing circulating
      inflammatory cells that infiltrate atherosclerotic lesions.

PMID- 22144567
TI  - Using stress testing to guide primary prevention of coronary heart disease among
      intermediate-risk patients: a cost-effectiveness analysis.
AB  - BACKGROUND: Noninvasive stress testing might guide the use of aspirin and statins
      for primary prevention of coronary heart disease, but it is unclear if such a
      strategy would be cost effective. METHODS AND RESULTS: We compared the status
      quo, in which the current national use of aspirin and statins was simulated, with
      3 other strategies: (1) full implementation of Adult Treatment Panel III
      guidelines, (2) a treat-all strategy in which all intermediate-risk persons
      received statins (men and women) and aspirin (men only), and (3) a test-and-treat
      strategy in which all persons with an intermediate risk of coronary heart disease
      underwent stress testing and those with a positive test were treated with high
      intensity statins (men and women) and aspirin (men only). Healthcare costs,
      coronary heart disease events, and quality-adjusted life years from 2011 to 2040
      were projected. Under a variety of assumptions, the treat-all strategy was the
      most effective and least expensive strategy. Stress electrocardiography was more
      effective and less expensive than other test-and-treat strategies, but it was
      less expensive than treat all only if statin cost exceeded $3.16/pill or if
      testing increased adherence from <22% to >75%. However, stress
      electrocardiography could be cost effective in persons initially nonadherent to
      the treat-all strategy if it raised their adherence to 5% and cost saving if it
      raised their adherence to 13%. CONCLUSIONS: When generic high-potency statins are
      available, noninvasive cardiac stress testing to target preventive medications is
      not cost effective unless it substantially improves adherence.

PMID- 22144568
TI  - A2b adenosine receptor regulates hyperlipidemia and atherosclerosis.
AB  - BACKGROUND: The cAMP-elevating A(2b) adenosine receptor (A(2b)AR) controls
      inflammation via its expression in bone marrow cells. METHODS AND RESULTS:
      Atherosclerosis induced by a high-fat diet in apolipoprotein E-deficient mice was
      more pronounced in the absence of the A(2b)AR. Bone marrow transplantation
      experiments indicated that A(2b)AR bone marrow cell signals alone were not
      sufficient to elicit this effect. Intriguingly, liver expression of the A(2b)AR
      in wild-type mice was vastly augmented by a high-fat diet, raising the
      possibility that this upregulation is of functional significance. A(2b)AR genetic
      ablation led to elevated levels of liver and plasma cholesterol and triglycerides
      and to fatty liver pathology typical of steatosis, assessed by enzymatic assays
      and analysis of liver sections. Western blotting and quantitative polymerase
      chain reaction revealed elevated expression of the following molecules in the
      liver of A(2b)AR-null mice: the transcription factor sterol regulatory element
      binding protein-1 (SREBP-1) and its 2 downstream targets and regulators of
      lipogenesis, acetyl CoA carboxylase and fatty acid synthase. Pharmacological
      activation or inhibition of A(2b)AR in primary hepatocytes confirmed the
      regulation of SREBP-1 by this receptor. A(2b)AR-mediated changes in cAMP were
      found to regulate levels of the transcriptionally active form of SREBP-1.
      Finally, adenovirally mediated restoration of the A(2b)AR in the liver of A(2b)AR
      null mice reduced the lipid profile and atherosclerosis. Similarly, in vivo
      administration of the A(2b)AR ligand BAY 60-6853 in control mice on a high-fat
      diet reduced the lipid profile and atherosclerosis. CONCLUSION: This study
      provides the first evidence that the A(2b)AR regulates liver SREBP-1,
      hyperlipidemia, and atherosclerosis, suggesting that this receptor may be an
      effective therapeutic target.

PMID- 22144570
TI  - 2012 ACCF/AHA/ACR/SCAI/SIR/STS/SVM/SVN/SVS key data elements and definitions for
      peripheral atherosclerotic vascular disease: a report of the American College of
      Cardiology Foundation/American Heart Association Task Force on Clinical Data
      Standards (Writing Committee to Develop Clinical Data Standards for Peripheral
      Atherosclerotic Vascular Disease).

PMID- 22144569
TI  - Migraine mutations increase stroke vulnerability by facilitating ischemic
      depolarizations.
AB  - BACKGROUND: Migraine is an independent risk factor for stroke. Mechanisms
      underlying this association are unclear. Familial hemiplegic migraine (FHM), a
      migraine subtype that also carries an increased stroke risk, is a useful model
      for common migraine phenotypes because of shared aura and headache features,
      trigger factors, and underlying glutamatergic mechanisms. METHODS AND RESULTS:
      Here, we show that FHM type 1 (FHM1) mutations in Ca(V)2.1 voltage-gated Ca(2+)
      channels render the brain more vulnerable to ischemic stroke. Compared with wild
      type mice, 2 FHM1 mutant mouse strains developed earlier onset of anoxic
      depolarization and more frequent peri-infarct depolarizations associated with
      rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging
      and larger perfusion deficits on laser speckle flowmetry. Cerebral blood flow
      required for tissue survival was higher in the mutants, leading to infarction
      with milder ischemia. As a result, mutants developed larger infarcts and worse
      neurological outcomes after stroke, which were selectively attenuated by a
      glutamate receptor antagonist. CONCLUSIONS: We propose that enhanced
      susceptibility to ischemic depolarizations akin to spreading depression
      predisposes migraineurs to infarction during mild ischemic events, thereby
      increasing the stroke risk.

PMID- 22144571
TI  - Mitochondrial thioredoxin reductase is essential for early postischemic
      myocardial protection.
AB  - BACKGROUND: Excessive formation of reactive oxygen species contributes to tissue
      injury and functional deterioration after myocardial ischemia/reperfusion.
      Especially, mitochondrial reactive oxygen species are capable of opening the
      mitochondrial permeability transition pore, a harmful event in cardiac
      ischemia/reperfusion. Thioredoxins are key players in the cardiac defense against
      oxidative stress. Mutations in the mitochondrial thioredoxin reductase
      (thioredoxin reductase-2, Txnrd2) gene have been recently identified to cause
      dilated cardiomyopathy in patients. Here, we investigated whether mitochondrial
      thioredoxin reductase is protective against myocardial ischemia/reperfusion
      injury. METHODS AND RESULTS: In mice, alpha-MHC-restricted Cre-mediated Txnrd2
      deficiency, induced by tamoxifen (Txnrd2-/-ic), aggravated systolic dysfunction
      and cardiomyocyte cell death after ischemia (90 minutes) and reperfusion (24
      hours). Txnrd2-/-ic was accompanied by a loss of mitochondrial integrity and
      function, which was resolved on pretreatment with the reactive oxygen species
      scavenger N-acetylcysteine and the mitochondrial permeability transition pore
      blocker cyclosporin A. Likewise, Txnrd2 deletion in embryonic endothelial
      precursor cells and embryonic stem cell-derived cardiomyocytes, as well as
      introduction of Txnrd2-shRNA into adult HL-1 cardiomyocytes, increased cell death
      on hypoxia and reoxygenation, unless N-acetylcysteine was coadministered.
      CONCLUSIONS: We report that Txnrd2 exerts a crucial function during postischemic
      reperfusion via thiol regeneration. The efficacy of cyclosporin A in cardiac
      Txnrd2 deficiency may indicate a role for Txnrd2 in reducing mitochondrial
      reactive oxygen species, thereby preventing opening of the mitochondrial
      permeability transition pore.

PMID- 22144572
TI  - Loss of myeloid related protein-8/14 exacerbates cardiac allograft rejection.
AB  - BACKGROUND: The calcium-binding proteins myeloid-related protein (MRP)-8 (S100A8)
      and MRP-14 (S100A9) form MRP-8/14 heterodimers (S100A8/A9, calprotectin) that
      regulate myeloid cell function and inflammatory responses and serve as early
      serum markers for monitoring acute allograft rejection. Despite functioning as a
      proinflammatory mediator, the pathophysiological role of MRP-8/14 complexes in
      cardiovascular disease is incompletely defined. This study investigated the role
      of MRP-8/14 in cardiac allograft rejection using MRP-14(-/-) mice that lack MRP
      8/14 complexes. METHODS AND RESULTS: We examined parenchymal rejection after
      major histocompatibility complex class II allomismatched cardiac transplantation
      (bm12 donor heart and B6 recipients) in wild-type (WT) and MRP-14(-/-)
      recipients. Allograft survival averaged 5.9+/-2.9 weeks (n=10) in MRP-14(-/-)
      recipients compared with >12 weeks (n=15; P<0.0001) in WT recipients. Two weeks
      after transplantation, allografts in MRP-14(-/-) recipients had significantly
      higher parenchymal rejection scores (2.8+/-0.8; n=8) than did WT recipients
      (0.8+/-0.8; n=12; P<0.0001). Compared with WT recipients, allografts in MRP-14(-/
      ) recipients had significantly increased T-cell and macrophage infiltration and
      increased mRNA levels of interferon-gamma and interferon-gamma-associated
      chemokines (CXCL9, CXCL10, and CXCL11), interleukin-6, and interleukin-17 with
      significantly higher levels of Th17 cells. MRP-14(-/-) recipients also had
      significantly more lymphocytes in the adjacent para-aortic lymph nodes than did
      WT recipients (cells per lymph node: 23.7+/-0.7*10(5) for MRP-14(-/-) versus
      6.0+/-0.2*10(5) for WT; P<0.0001). The dendritic cells (DCs) of the MRP-14(-/-)
      recipients of bm12 hearts expressed significantly higher levels of the
      costimulatory molecules CD80 and CD86 than did those of WT recipients 2 weeks
      after transplantation. Mixed leukocyte reactions with allo-endothelial cell
      primed MRP-14(-/-) DCs resulted in significantly higher antigen-presenting
      function than reactions using WT DCs. Ovalbumin-primed MRP-14(-/-) DCs augmented
      proliferation of OT-II (ovalbumin-specific T cell receptor transgenic) CD4(+) T
      cells with increased interleukin-2 and interferon-gamma production. Cardiac
      allografts of B6 major histocompatibility complex class II(-/-) hosts and of B6
      WT hosts receiving MRP-14(-/-) DCs had significantly augmented inflammatory cell
      infiltration and accelerated allograft rejection compared with WT DCs from
      transferred recipient allografts. Bone marrow-derived MRP-14(-/-) DCs infected
      with MRP-8 and MRP-14 retroviral vectors showed significantly decreased CD80 and
      CD86 expression compared with controls, indicating that MRP-8/14 regulates B7
      costimulatory molecule expression. CONCLUSIONS: Our results indicate that MRP-14
      regulates B7 molecule expression and reduces antigen presentation by DCs and
      subsequent T-cell priming. The absence of MRP-14 markedly increased T-cell
      activation and exacerbated allograft rejection, indicating a previously
      unrecognized role for MRP-14 in immune cell biology.

PMID- 22144575
TI  - Repetitive activity slows axonal conduction velocity and concomitantly increases
      mechanical activation threshold in single axons of the rat cranial dura.
AB  - The passage of an action potential along a peripheral axon modulates the
      conduction velocity of subsequent action potentials. In C-neurones with
      unmyelinated axons repetitive activity progressively slows axonal conduction
      velocity and in microneurographic recordings from healthy human subjects the
      magnitude of this slowing can be used to predict the receptive properties of
      individual axons. Recently, a reduction in the number of available voltage-gated
      sodium channels (Na(V)) through inactivation has been implicated as the
      predominant factor responsible for the slowing of axonal conduction. Since Na(V)s
      are also responsible for the initiation of action potentials in sensory nerve
      terminals, changes in their availability may be expected to affect activation
      threshold for sensory stimuli. To examine this proposal, dynamic mechanical
      stimuli were used to make precise estimates of activation threshold in single
      unmyelinated axons innervating the rat cranial dura mater. Decreases in axonal
      conduction velocity induced by repetitive electrical stimulation were paralleled
      by an increase in mechanical activation threshold. Application of TTX (10-20 nM)
      also slowed axonal conduction velocity in all 11 fibres examined and in 9 of
      these this resulted in a parallel increase in mechanical activation threshold. We
      interpret this as indicating that a reduction in available Na(V) number
      contributes to both axonal conduction velocity slowing and the observed parallel
      increase in mechanical activation threshold. The slowing of axonal conduction
      velocity observed during repetitive activity thus represents a form of
      accommodation, i.e. self inhibition, which is likely to be decisive in limiting
      peripheral input to the spinal dorsal horn and thereby regulating processes that
      could otherwise lead to central sensitization.

PMID- 22144574
TI  - Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve
      diastolic distensibility in vivo.
AB  - BACKGROUND: In vitro studies suggest that phosphorylation of titin reduces
      myocyte/myofiber stiffness. Titin can be phosphorylated by cGMP-activated protein
      kinase. Intracellular cGMP production is stimulated by B-type natriuretic peptide
      (BNP) and degraded by phosphodiesterases, including phosphodiesterase-5A. We
      hypothesized that a phosphodiesterase-5A inhibitor (sildenafil) alone or in
      combination with BNP would increase left ventricular diastolic distensibility by
      phosphorylating titin. METHODS AND RESULTS: Eight elderly dogs with experimental
      hypertension and 4 young normal dogs underwent measurement of the end-diastolic
      pressure-volume relationship during caval occlusion at baseline, after
      sildenafil, and BNP infusion. To assess diastolic distensibility independently of
      load/extrinsic forces, the end-diastolic volume at a common end-diastolic
      pressure on the sequential end-diastolic pressure-volume relationships was
      measured (left ventricular capacitance). In a separate group of dogs (n=7 old
      hypertensive and 7 young normal), serial full-thickness left ventricular biopsies
      were harvested from the beating heart during identical infusions to measure
      myofilament protein phosphorylation. Plasma cGMP increased with sildenafil and
      further with BNP (7.31+/-2.37 to 26.9+/-10.3 to 70.3+/-8.1 pmol/mL; P<0.001).
      Left ventricular diastolic capacitance increased with sildenafil and further with
      BNP (51.4+/-16.9 to 53.7+/-16.8 to 60.0+/-19.4 mL; P<0.001). Changes were similar
      in old hypertensive and young normal dogs. There were no effects on
      phosphorylation of troponin I, troponin T, phospholamban, or myosin light chain-1
      or -2. Titin phosphorylation increased with sildenafil and BNP, whereas titin
      based cardiomyocyte stiffness decreased. CONCLUSION: Short-term cGMP-enhancing
      treatment with sildenafil and BNP improves left ventricular diastolic
      distensibility in vivo, in part by phosphorylating titin.

PMID- 22144576
TI  - Augmented single-unit muscle sympathetic nerve activity in heart failure with
      chronic atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common complication in heart failure (HF) patients.
      However, it remains unclear whether irregular ventricular response patterns
      induced by AF increase sympathetic nerve activity. We measured resting multi- and
      single-unit muscle sympathetic nerve activity (MSNA) in 21 age-matched HF
      patients with chronic AF (n = 11) rhythm or sinus rhythm (SR, n = 10). The multi
      unit MSNA, which was expressed as total activity, was similar between HF + AF
      patients and HF + SR patients. However, the single-unit MSNA in HF + AF patients
      was significantly greater than that in HF + SR patients (62 +/- 9 spikes min(-1)
      vs. 42 +/- 4 spikes min(-1), P < 0.05). Moreover, the incidence of multiple
      firing of single-unit MSNA within a given burst was augmented in HF + AF patients
      as compared with HF + SR patients (48 +/- 8% vs. 26 +/- 3%, P < 0.01). A
      significant negative relationship was observed between the reduced diastolic
      pressure induced by a prolonged cardiac interval in AF subjects and single-unit
      MSNA frequency within one cardiac interval in each HF + AF subject. The firing
      characteristics of single-unit MSNA were different between HF patients with AF
      and HF patients with SR; particularly, those with a prolonged long RR interval
      showed multiple firings of single-unit MSNA. These findings suggest that AF per
      se leads to the instantaneous augmentation of single-unit MSNA induced by
      decreased diastolic pressure, which might partially contribute to disease
      progression in HF patients.

PMID- 22144573
TI  - Genome-wide association study for coronary artery calcification with follow-up in
      myocardial infarction.
AB  - BACKGROUND: Coronary artery calcification (CAC) detected by computed tomography
      is a noninvasive measure of coronary atherosclerosis, which underlies most cases
      of myocardial infarction (MI). We sought to identify common genetic variants
      associated with CAC and further investigate their associations with MI. METHODS
      AND RESULTS: Computed tomography was used to assess quantity of CAC. A meta
      analysis of genome-wide association studies for CAC was performed in 9961 men and
      women from 5 independent community-based cohorts, with replication in 3
      additional independent cohorts (n=6032). We examined the top single-nucleotide
      polymorphisms (SNPs) associated with CAC quantity for association with MI in
      multiple large genome-wide association studies of MI. Genome-wide significant
      associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top
      SNP: rs1333049; P=7.58*10(-19)) and 6p24 (top SNP: rs9349379, within the PHACTR1
      gene; P=2.65*10(-11)) replicated for CAC and for MI. Additionally, there is
      evidence for concordance of SNP associations with both CAC and MI at a number of
      other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13
      (SORT1 gene). CONCLUSIONS: SNPs in the 9p21 and PHACTR1 gene loci were strongly
      associated with CAC and MI, and there are suggestive associations with both CAC
      and MI of SNPs in additional loci. Multiple genetic loci are associated with
      development of both underlying coronary atherosclerosis and clinical events.

PMID- 22144577
TI  - Hedgehog signalling in gut development, physiology and cancer.
AB  - The Hedgehog pathway is one of the most common signal transduction pathways used
      by mammalian cells. Most studies have focused on its role during development,
      primarily of the nervous system, skin, bone and pancreas. Due to the activation
      of this pathway during proliferation and neoplastic transformation, more recent
      studies have examined its role in adult tissues. Significant levels of sonic
      hedgehog are expressed in the gastric mucosa, which has served to direct analysis
      of its role during organogenesis, gastric acid secretion and neoplastic
      transformation. Therefore the goal of this review is to apply current knowledge
      of this pathway to further our understanding of gastrointestinal physiology and
      neoplasia, using the stomach as a prototype.

PMID- 22144578
TI  - VAMP8 is a vesicle SNARE that regulates mucin secretion in airway goblet cells.
AB  - Mucin secretion is an innate defence mechanism, which is noxiously upregulated in
      obstructive lung diseases (e.g. chronic obstructive pulmonary disease (COPD),
      cystic fibrosis and asthma). Mucin granule exocytosis is regulated by specific
      protein complexes, but the SNARE exocytotic core has not been defined in airway
      goblet cells. In this study, we identify VAMP8 as one of the SNAREs regulating
      mucin granule exocytosis. VAMP8 mRNA was present in human airway and lung
      epithelial cells, and deep-sequencing and expression analyses of airway
      epithelial cells revealed that VAMP8 transcripts were expressed at 10 times
      higher levels than other VAMP mRNAs. In human airway epithelial cell cultures and
      freshly excised tissues, VAMP8 immunolocalised mainly to goblet cell mucin
      granules. The function of VAMP8 in airway mucin secretion was tested by RNA
      interference techniques. Both VAMP8 short interfering RNAs (siRNAs) and short
      hairpin RNAs (shRNAs) reduced mucin secretion induced by PAR agonists, neutrophil
      elastase and ATP in two airway epithelial cell culture models. Notably, basal
      (non-agonist elicited) mucin secretion was also reduced in these experiments.
      VAMP8 knockdown was also effective in decreasing mucin secretion in airway
      epithelial cell cultures with induced mucous metaplasia/mucin hypersecretion.
      Unlike VAMP8 silencing, knockdown of VAMP2 or VAMP3 did not affect mucin
      secretion. Importantly, in VAMP8 knock-out (KO) mice with IL-13-induced mucous
      metaplasia, mucin content in the bronchoalveolar lavage (BAL) and ATP-stimulated
      mucin secretion in the trachea were reduced compared to WT-matched littermates.
      Our data indicate that VAMP8 is an essential SNARE in airway mucin granule
      exocytosis. Reduction of VAMP8 activity/expression may provide a novel
      therapeutic target to ameliorate airway mucus obstruction in lung diseases.

PMID- 22144579
TI  - Cardio-renal and metabolic adaptations during pregnancy in female rats born
      small: implications for maternal health and second generation fetal growth.
AB  - Intrauterine growth restriction caused by uteroplacental insufficiency increases
      risk of cardiovascular and metabolic disease in offspring. Cardio-renal and
      metabolic responses to pregnancy are critical determinants of immediate and long
      term maternal health. However, no studies to date have investigated the renal and
      metabolic adaptations in growth restricted offspring when they in turn become
      pregnant. We hypothesised that the physiological challenge of pregnancy in growth
      restricted females exacerbates disease outcome and compromises next generation
      fetal growth. Uteroplacental insufficiency was induced by bilateral uterine
      vessel ligation (Restricted) or sham surgery (Control) on day 18 of gestation in
      WKY rats and F1 female offspring birth and postnatal body weights were recorded.
      F1 Control and Restricted females were mated at 4 months and blood pressure,
      renal and metabolic parameters were measured in late pregnancy and F2 fetal and
      placental weights recorded. Age-matched non-pregnant Control and Restricted F1
      females were also studied. F1 Restricted females were born 10-15% lighter than
      Controls. Basal insulin secretion and pancreatic beta-cell mass were reduced in
      non-pregnant Restricted females but restored in pregnancy. Pregnant Restricted
      females, however, showed impaired glucose tolerance and compensatory glomerular
      hypertrophy, with a nephron deficit but normal renal function and blood pressure.
      F2 fetuses from Restricted mothers exposed to physiological measures during
      pregnancy were lighter than Controls highlighting additive adverse effects when
      mothers born small experience stress during pregnancy. Female rats born small
      exhibit mostly normal cardio-renal adaptations but altered glucose control during
      late pregnancy making them vulnerable to lifestyle challenges.

PMID- 22144580
TI  - Chest wall dynamics during voluntary and induced cough in healthy volunteers.
AB  - Coughing both protects the airways from foreign material and clears excessive
      secretions in respiratory diseases, and therefore requires high expiratory flows.
      We hypothesised that the volume inspired prior to coughing (operating volume)
      would significantly influence the mechanical changes during coughing and thus
      cough flow. Sixteen healthy volunteers (6 female, mean age 31 +/- 10 years)
      performed six single voluntary coughs from four different operating volumes (10%,
      30%, 60% and 90% of vital capacity) followed by three peals of voluntary and
      citric acid-induced coughs. During coughing we simultaneously measured (i) chest
      and upper abdominal wall motion using opto-electronic plethysmography (OEP), (ii)
      intra-thoracic and intra-abdominal pressures with a balloon catheter in each
      compartment and (iii) flow at the mouth. Operating volume was the most important
      determinant of the peak flow achieved and volume expelled during coughing, but
      had little influence on the pressures generated. The duration of single coughs
      increased with operating volume, whereas coughs were much shorter and varied
      little during peals. Voluntary cough peals were also associated with significant
      blood shift away from the trunk. In conclusion, this study has shown that
      operating volume is the most important determinant of cough peak flow and volume
      expelled in healthy individuals. During peals of coughs, similar mechanical
      effects were achieved more rapidly, suggesting a modification of the motor
      pattern with improved efficiency. Future studies investigating cough mechanics in
      health and disease should control for the influence of operating volume.

PMID- 22144581
TI  - Dopamine-regulated microRNA MiR-181a controls GluA2 surface expression in
      hippocampal neurons.
AB  - The dynamic expression of AMPA-type glutamate receptors (AMPA-R) at synapses is a
      key determinant of synaptic plasticity, including neuroadaptations to drugs of
      abuse. Recently, microRNAs (miRNAs) have emerged as important posttranscriptional
      regulators of synaptic plasticity, but whether they target glutamate receptors to
      mediate this effect is not known. Here we used microarray screening to identify
      miRNAs that regulate synaptic plasticity within the nucleus accumbens, a brain
      region critical to forming drug-seeking habits. One of the miRNAs that showed a
      robust enrichment at medium spiny neuron synapses was miR-181a. Using
      bioinformatics tools, we detected a highly conserved miR-181a binding site within
      the mRNA encoding the GluA2 subunit of AMPA-Rs. Overexpression and knockdown of
      miR-181a in primary neurons demonstrated that this miRNA is a negative
      posttranscriptional regulator of GluA2 expression. Additionally, miR-181a
      overexpression reduced GluA2 surface expression, spine formation, and miniature
      excitatory postsynaptic current (mEPSC) frequency in hippocampal neurons,
      suggesting that miR-181a could regulate synaptic function. Moreover, miR-181a
      expression was induced by dopamine signaling in primary neurons, as well as by
      cocaine and amphetamines, in a mouse model of chronic drug treatment. Taken
      together, our results identify miR-181a as a key regulator of mammalian AMPA-type
      glutamate receptors, with potential implications for the regulation of drug
      induced synaptic plasticity.

PMID- 22144582
TI  - Conserved molecular interactions within the HBO1 acetyltransferase complexes
      regulate cell proliferation.
AB  - Acetyltransferase complexes of the MYST family with distinct substrate
      specificities and functions maintain a conserved association with different ING
      tumor suppressor proteins. ING complexes containing the HBO1 acetylase are a
      major source of histone H3 and H4 acetylation in vivo and play critical roles in
      gene regulation and DNA replication. Here, our molecular dissection of HBO1/ING
      complexes unravels the protein domains required for their assembly and function.
      Multiple PHD finger domains present in different subunits bind the histone H3 N
      terminal tail with a distinct specificity toward lysine 4 methylation status. We
      show that natively regulated association of the ING4/5 PHD domain with HBO1-JADE
      determines the growth inhibitory function of the complex, linked to its tumor
      suppressor activity. Functional genomic analyses indicate that the p53 pathway is
      a main target of the complex, at least in part through direct transcription
      regulation at the initiation site of p21/CDKN1A. These results demonstrate the
      importance of ING association with MYST acetyltransferases in controlling cell
      proliferation, a regulated link that accounts for the reported tumor suppressor
      activities of these complexes.

PMID- 22144584
TI  - Addressing scientific fraud.

PMID- 22144589
TI  - Intellectual property. Dispute over lab notebooks lands researcher in jail.

PMID- 22144583
TI  - MicroRNA-200c represses migration and invasion of breast cancer cells by
      targeting actin-regulatory proteins FHOD1 and PPM1F.
AB  - MicroRNA-200c (miR-200c) has been shown to suppress epithelial-mesenchymal
      transition (EMT), which is attributed mainly to targeting of ZEB1/ZEB2,
      repressors of the cell-cell contact protein E-cadherin. Here we demonstrated that
      modulation of miR-200c in breast cancer cells regulates cell migration, cell
      elongation, and transforming growth factor beta (TGF-beta)-induced stress fiber
      formation by impacting the reorganization of cytoskeleton that is independent of
      the ZEB/E-cadherin axis. We identified FHOD1 and PPM1F, direct regulators of the
      actin cytoskeleton, as novel targets of miR-200c. Remarkably, expression levels
      of FHOD1 and PPM1F were inversely correlated with the level of miR-200c in breast
      cancer cell lines, breast cancer patient samples, and 58 cancer cell lines of
      various origins. Furthermore, individual knockdown/overexpression of these target
      genes phenocopied the effects of miR-200c overexpression/inhibition on cell
      elongation, stress fiber formation, migration, and invasion. Mechanistically,
      targeting of FHOD1 by miR-200c resulted in decreased expression and
      transcriptional activity of serum response factor (SRF), mediated by interference
      with the translocation of the SRF coactivator mycocardin-related transcription
      factor A (MRTF-A). This finally led to downregulation of the expression and
      phosphorylation of the SRF target myosin light chain 2 (MLC2) gene, required for
      stress fiber formation and contractility. Thus, miR-200c impacts on metastasis by
      regulating several EMT-related processes, including a novel mechanism involving
      the direct targeting of actin-regulatory proteins.

PMID- 22144590
TI  - Broadening participation. Berkeley engineering students demand greater effort to
      promote diversity.

PMID- 22144591
TI  - Infectious diseases. Controversial studies give a deadly flu virus wings.

PMID- 22144592
TI  - Genetics. Aging genes: the sirtuin story unravels.

PMID- 22144593
TI  - Glaciology. 'Third pole' glacier research gets a boost from China.

PMID- 22144594
TI  - Superluminal neutrinos. Where does the time go?

PMID- 22144595
TI  - Retraction.

PMID- 22144597
TI  - Top-flight safety model for nuclear industry.

PMID- 22144596
TI  - Lobsters at bat.

PMID- 22144603
TI  - Information science. Better data for a better Internet.

PMID- 22144601
TI  - Comment on "Preserved feedforward but impaired top-down processes in the
      vegetative state".
AB  - Boly et al. (Reports, 13 May 2011, p. 858) investigated cortical connectivity
      patterns in patients suffering from a disorder of consciousness, using
      electroencephalography in an auditory oddball paradigm. We point to several
      inconsistencies in their data, including a failure to replicate the classical
      mismatch negativity. Data quality, source reconstruction, and statistics would
      need to be improved to support their conclusions.

PMID- 22144604
TI  - Cell biology. Yeast informs Alzheimer's disease.

PMID- 22144605
TI  - Physics. Quantum correlation between distant diamonds.

PMID- 22144606
TI  - Ecology. Mathematical Dances with wolves.

PMID- 22144607
TI  - Astronomy. The pristine universe.

PMID- 22144608
TI  - Medicine. Personalized cancer diagnostics.

PMID- 22144609
TI  - Cell biology. Warburg effect and redox balance.

PMID- 22144610
TI  - Sociology. Experimenting with buddies.

PMID- 22144611
TI  - GE Prize essay. Zoom!

PMID- 22144612
TI  - Data replication & reproducibility. Again, and again, and again ....
      Introduction.

PMID- 22144613
TI  - Reproducible research in computational science.
AB  - Computational science has led to exciting new developments, but the nature of the
      work has exposed limitations in our ability to evaluate published findings.
      Reproducibility has the potential to serve as a minimum standard for judging
      scientific claims when full independent replication of a study is not possible.

PMID- 22144614
TI  - Methodological challenges in the study of primate cognition.
AB  - Laboratory studies of primate cognition face the problem that captive populations
      of a species are not always comparable, and generalizations to natural
      populations are never certain. Studies of primate cognition in the field face the
      problem that replications are expensive and difficult, and again different
      populations are not always comparable. To help remedy these problems, we
      recommend the creation of data banks where primary data and videotapes may be
      deposited (perhaps as a requirement of publication) to facilitate cross
      examination, replication, and, eventually, the pooling of data across
      investigators.

PMID- 22144615
TI  - Replication in field biology: the case of the frog-eating bat.
AB  - Studies conducted in the field offer unique opportunities to observe nature, but
      achieving true replication under natural conditions is challenging. As
      demonstrated by the discovery of frog eating by a charismatic bat, biology
      conducted in the field generally follows an interesting progression that includes
      discovery, demonstration, experimentation, and verification.

PMID- 22144616
TI  - Improving validation practices in "omics" research.
AB  - "Omics" research poses acute challenges regarding how to enhance validation
      practices and eventually the utility of this rich information. Several strategies
      may be useful, including routine replication, public data and protocol
      availability, funding incentives, reproducibility rewards or penalties, and
      targeted repeatability checks.

PMID- 22144617
TI  - The reproducibility of observational estimates of surface and atmospheric
      temperature change.
AB  - Although concerns have been expressed about the reliability of surface
      temperature data sets, findings of pronounced surface warming over the past 60
      years have been independently reproduced by multiple groups. In contrast, an
      initial finding that the lower troposphere cooled since 1979 could not be
      reproduced. Attempts to confirm this apparent cooling trend led to the discovery
      of errors in the initial analyses of satellite-based tropospheric temperature
      measurements.

PMID- 22144618
TI  - The race to x-ray microbeam and nanobeam science.
AB  - X-ray microbeams are an emerging characterization tool with broad implications
      for science, ranging from materials structure and dynamics, to geophysics and
      environmental science, to biophysics and protein crystallography. We describe how
      submicrometer hard x-ray beams with the ability to penetrate tens to hundreds of
      micrometers into most materials and with the ability to determine local
      composition, chemistry, and (crystal) structure can characterize buried sample
      volumes and small samples in their natural or extreme environments. Beams less
      than 10 nanometers have already been demonstrated, and the practical limit for
      hard x-ray beam size, the limit to trace-element sensitivity, and the ultimate
      limitations associated with near-atomic structure determinations are the subject
      of ongoing research.

PMID- 22144619
TI  - The 2011 Tohoku-Oki earthquake: displacement reaching the trench axis.
AB  - We detected and measured coseismic displacement caused by the 11 March 2011
      Tohoku-Oki earthquake [moment magnitude (M(W)) 9.0] by using multibeam
      bathymetric surveys. The difference between bathymetric data acquired before and
      after the earthquake revealed that the displacement extended out to the axis of
      the Japan Trench, suggesting that the fault rupture reached the trench axis. The
      sea floor on the outermost landward area moved about 50 meters horizontally east
      southeast and ~10 meters upward. The large horizontal displacement lifted the sea
      floor by up to 16 meters on the landward slope in addition to the vertical
      displacement.

PMID- 22144620
TI  - Entangling macroscopic diamonds at room temperature.
AB  - Quantum entanglement in the motion of macroscopic solid bodies has implications
      both for quantum technologies and foundational studies of the boundary between
      the quantum and classical worlds. Entanglement is usually fragile in room
      temperature solids, owing to strong interactions both internally and with the
      noisy environment. We generated motional entanglement between vibrational states
      of two spatially separated, millimeter-sized diamonds at room temperature. By
      measuring strong nonclassical correlations between Raman-scattered photons, we
      showed that the quantum state of the diamonds has positive concurrence with 98%
      probability. Our results show that entanglement can persist in the classical
      context of moving macroscopic solids in ambient conditions.

PMID- 22144621
TI  - Enhancing hydrogen evolution activity in water splitting by tailoring Li+-Ni(OH)2
      Pt interfaces.
AB  - Improving the sluggish kinetics for the electrochemical reduction of water to
      molecular hydrogen in alkaline environments is one key to reducing the high
      overpotentials and associated energy losses in water-alkali and chlor-alkali
      electrolyzers. We found that a controlled arrangement of nanometer-scale
      Ni(OH)(2) clusters on platinum electrode surfaces manifests a factor of 8
      activity increase in catalyzing the hydrogen evolution reaction relative to state
      of-the-art metal and metal-oxide catalysts. In a bifunctional effect, the edges
      of the Ni(OH)(2) clusters promoted the dissociation of water and the production
      of hydrogen intermediates that then adsorbed on the nearby Pt surfaces and
      recombined into molecular hydrogen. The generation of these hydrogen
      intermediates could be further enhanced via Li(+)-induced destabilization of the
      HO-H bond, resulting in a factor of 10 total increase in activity.

PMID- 22144622
TI  - The role of carbon dioxide during the onset of Antarctic glaciation.
AB  - Earth's modern climate, characterized by polar ice sheets and large equator-to
      pole temperature gradients, is rooted in environmental changes that promoted
      Antarctic glaciation ~33.7 million years ago. Onset of Antarctic glaciation
      reflects a critical tipping point for Earth's climate and provides a framework
      for investigating the role of atmospheric carbon dioxide (CO(2)) during major
      climatic change. Previously published records of alkenone-based CO(2) from high-
      and low-latitude ocean localities suggested that CO(2) increased during
      glaciation, in contradiction to theory. Here, we further investigate alkenone
      records and demonstrate that Antarctic and subantarctic data overestimate
      atmospheric CO(2) levels, biasing long-term trends. Our results show that CO(2)
      declined before and during Antarctic glaciation and support a substantial CO(2)
      decrease as the primary agent forcing Antarctic glaciation, consistent with model
      derived CO(2) thresholds.

PMID- 22144623
TI  - Interhemispheric ice-sheet synchronicity during the Last Glacial Maximum.
AB  - The timing of the last maximum extent of the Antarctic ice sheets relative to
      those in the Northern Hemisphere remains poorly understood. We develop a
      chronology for the Weddell Sea sector of the East Antarctic Ice Sheet that,
      combined with ages from other Antarctic ice-sheet sectors, indicates that the
      advance to and retreat from their maximum extent was within dating uncertainties
      synchronous with most sectors of Northern Hemisphere ice sheets. Surface climate
      forcing of Antarctic mass balance would probably cause an opposite response,
      whereby a warming climate would increase accumulation but not surface melting.
      Our new data support teleconnections involving sea-level forcing from Northern
      Hemisphere ice sheets and changes in North Atlantic deep-water formation and
      attendant heat flux to Antarctic grounding lines to synchronize the hemispheric
      ice sheets.

PMID- 22144624
TI  - An experimental study of homophily in the adoption of health behavior.
AB  - How does the composition of a population affect the adoption of health behaviors
      and innovations? Homophily--similarity of social contacts--can increase dyadic
      level influence, but it can also force less healthy individuals to interact
      primarily with one another, thereby excluding them from interactions with
      healthier, more influential, early adopters. As a result, an important network
      level effect of homophily is that the people who are most in need of a health
      innovation may be among the least likely to adopt it. Despite the importance of
      this thesis, confounding factors in observational data have made it difficult to
      test empirically. We report results from a controlled experimental study on the
      spread of a health innovation through fixed social networks in which the level of
      homophily was independently varied. We found that homophily significantly
      increased overall adoption of a new health behavior, especially among those most
      in need of it.

PMID- 22144625
TI  - Specialized face learning is associated with individual recognition in paper
      wasps.
AB  - We demonstrate that the evolution of facial recognition in wasps is associated
      with specialized face-learning abilities. Polistes fuscatus can differentiate
      among normal wasp face images more rapidly and accurately than nonface images or
      manipulated faces. A close relative lacking facial recognition, Polistes
      metricus, however, lacks specialized face learning. Similar specializations for
      face learning are found in primates and other mammals, although P. fuscatus
      represents an independent evolution of specialization. Convergence toward face
      specialization in distant taxa as well as divergence among closely related taxa
      with different recognition behavior suggests that specialized cognition is
      surprisingly labile and may be adaptively shaped by species-specific selective
      pressures such as face recognition.

PMID- 22144626
TI  - Modeling effects of environmental change on wolf population dynamics, trait
      evolution, and life history.
AB  - Environmental change has been observed to generate simultaneous responses in
      population dynamics, life history, gene frequencies, and morphology in a number
      of species. But how common are such eco-evolutionary responses to environmental
      change likely to be? Are they inevitable, or do they require a specific type of
      change? Can we accurately predict eco-evolutionary responses? We address these
      questions using theory and data from the study of Yellowstone wolves. We show
      that environmental change is expected to generate eco-evolutionary change, that
      changes in the average environment will affect wolves to a greater extent than
      changes in how variable it is, and that accurate prediction of the consequences
      of environmental change will probably prove elusive.

PMID- 22144627
TI  - Robust crossover assurance and regulated interhomolog access maintain meiotic
      crossover number.
AB  - Most organisms rely on interhomolog crossovers (COs) to ensure proper meiotic
      chromosome segregation but make few COs per chromosome pair. By monitoring repair
      events at a defined double-strand break (DSB) site during Caenorhabditis elegans
      meiosis, we reveal mechanisms that ensure formation of the obligate CO while
      limiting CO number. We find that CO is the preferred DSB repair outcome in the
      absence of inhibitory effects of other (nascent) recombination events. Thus, a
      single DSB per chromosome pair is largely sufficient to ensure CO formation.
      Further, we show that access to the homolog as a repair template is regulated,
      shutting down simultaneously for both CO and noncrossover (NCO) pathways. We
      propose that regulation of interhomolog access limits CO number and contributes
      to CO interference.

PMID- 22144629
TI  - ST-segment-elevation myocardial infarction treatment and the seductive lure of
      observational analyses.

PMID- 22144628
TI  - The intraepithelial T cell response to NKG2D-ligands links lymphoid stress
      surveillance to atopy.
AB  - Epithelial cells respond to physicochemical damage with up-regulation of major
      histocompatibility complex-like ligands that can activate the cytolytic potential
      of neighboring intraepithelial T cells by binding the activating receptor, NKG2D.
      The systemic implications of this lymphoid stress-surveillance response, however,
      are unknown. We found that antigens encountered at the same time as cutaneous
      epithelial stress induced strong primary and secondary systemic, T helper 2
      (T(H)2)-associated atopic responses in mice. These responses required NKG2D
      dependent communication between dysregulated epithelial cells and tissue
      associated lymphoid cells. These data are germane to uncertainty over the
      afferent induction of T(H)2 responses and provide a molecular framework for
      considering atopy as an important component of the response to tissue damage and
      carcinogenesis.

PMID- 22144630
TI  - Targeting proteases in atherosclerosis: hitting the nail with the hammer.

PMID- 22144632
TI  - Using pharmacogenetics in real time to guide warfarin initiation: a clinician
      update.

PMID- 22144633
TI  - Public policy approaches to the prevention of heart disease and stroke.

PMID- 22144631
TI  - Long-term effects of changes in cardiorespiratory fitness and body mass index on
      all-cause and cardiovascular disease mortality in men: the Aerobics Center
      Longitudinal Study.
AB  - BACKGROUND: The combined associations of changes in cardiorespiratory fitness and
      body mass index (BMI) with mortality remain controversial and uncertain. METHODS
      AND RESULTS: We examined the independent and combined associations of changes in
      fitness and BMI with all-cause and cardiovascular disease (CVD) mortality in 14
      345 men (mean age 44 years) with at least 2 medical examinations. Fitness, in
      metabolic equivalents (METs), was estimated from a maximal treadmill test. BMI
      was calculated using measured weight and height. Changes in fitness and BMI
      between the baseline and last examinations over 6.3 years were classified into
      loss, stable, or gain groups. During 11.4 years of follow-up after the last
      examination, 914 all-cause and 300 CVD deaths occurred. The hazard ratios (95%
      confidence intervals) of all-cause and CVD mortality were 0.70 (0.59-0.83) and
      0.73 (0.54-0.98) for stable fitness, and 0.61 (0.51-0.73) and 0.58 (0.42-0.80)
      for fitness gain, respectively, compared with fitness loss in multivariable
      analyses including BMI change. Every 1-MET improvement was associated with 15%
      and 19% lower risk of all-cause and CVD mortality, respectively. BMI change was
      not associated with all-cause or CVD mortality after adjusting for possible
      confounders and fitness change. In the combined analyses, men who lost fitness
      had higher all-cause and CVD mortality risks regardless of BMI change.
      CONCLUSIONS: Maintaining or improving fitness is associated with a lower risk of
      all-cause and CVD mortality in men. Preventing age-associated fitness loss is
      important for longevity regardless of BMI change.

PMID- 22144634
TI  - Brain death: evaluation of cerebral blood flow by use of arterial spin labeling.

PMID- 22144635
TI  - Renal angiomyolipoma with cardiac extension in patient with tuberous sclerosis
      complex.

PMID- 22144636
TI  - Low-flow/low-gradient aortic stenosis.

PMID- 22144638
TI  - Letter by Taylor et al regarding article, "Hydralazine and isosorbide dinitrate
      in heart failure: historical perspectives, mechanisms, and future directions".

PMID- 22144639
TI  - The evolution of multimeric protein assemblages.
AB  - Although the mechanisms by which complex cellular features evolve constitute one
      of the great unsolved problems of evolutionary biology, it is clear that the
      emergence of new protein-protein interactions, often accompanied by the
      diversification of duplicate genes, is involved. Using information on the levels
      of protein multimerization in major phylogenetic groups as a guide to the
      patterns that must be explained and relying on results from population-genetic
      theory to define the relative plausibility of alternative evolutionary pathways,
      a framework for understanding the evolution of dimers is developed. The resultant
      theory demonstrates that the likelihoods of alternative pathways for the
      emergence of protein complexes depend strongly on the effective population size.
      Nonetheless, it is equally clear that further advancements in this area will
      require comparative studies on the fitness consequences of alternative monomeric
      and dimeric proteins.

PMID- 22144640
TI  - Highly dynamic exon shuffling in candidate pathogen receptors ... what if brown
      algae were capable of adaptive immunity?
AB  - Pathogen recognition is the first step of immune reactions. In animals and
      plants, direct or indirect pathogen recognition is often mediated by a wealth of
      fast-evolving receptors, many of which contain ligand-binding and signal
      transduction domains, such as leucine-rich or tetratricopeptide repeat (LRR/TPR)
      and NB-ARC domains, respectively. In order to identify candidates potentially
      involved in algal defense, we mined the genome of the brown alga Ectocarpus
      siliculosus for homologues of these genes and assessed the evolutionary pressures
      acting upon them. We thus annotated all Ectocarpus LRR-containing genes, in
      particular an original group of LRR-containing GTPases of the ROCO family, and 24
      NB-ARC-TPR proteins. They exhibit high birth and death rates, while a
      diversifying selection is acting on their LRR (respectively TPR) domain, probably
      affecting the ligand-binding specificities. Remarkably, each repeat is encoded by
      an exon, and the intense exon shuffling underpins the variability of LRR and TPR
      domains. We conclude that the Ectocarpus ROCO and NB-ARC-TPR families are
      excellent candidates for being involved in recognition/transduction events linked
      to immunity. We further hypothesize that brown algae may generate their immune
      repertoire via controlled somatic recombination, so far only known from the
      vertebrate adaptive immune systems.

PMID- 22144642
TI  - eComment: Some points.

PMID- 22144641
TI  - Cost of antibiotic resistance and the geometry of adaptation.
AB  - The distribution of effects of beneficial mutations is key to our understanding
      of biological adaptation. Yet, empirical estimates of this distribution are
      scarce, and its functional form is largely unknown. Theoretical models of
      adaptation predict that the functional form of this distribution should depend on
      the distance to the optimum. Here, we estimate the rate and distribution of
      adaptive mutations that compensate for the effect of a single deleterious
      mutation, which causes antibiotic resistance. Using a system with multiple
      molecular markers, we estimate the distribution of fitness effects of mutations
      at two distances from the adaptive peak in 60 populations of Escherichia coli. We
      find that beneficial mutations, which can contribute to compensatory evolution,
      occur at very high rates, of the order of 10(-5) per genome per generation and
      can be detected within a few tens of generations. They cause an average fitness
      increase of 2.5% and 3.6%, depending on the cost of resistance, which is expected
      under Fisher's geometrical model of adaptation. Moreover, we provide the first
      description of the distribution of beneficial mutations, segregating during the
      process of compensatory evolution, to antibiotic resistances bearing different
      costs. Hence, these results have important implications to understanding the
      spread and maintenance of antibiotic resistance in bacteria.

PMID- 22144643
TI  - eComment: Advantage and judicial use of internal jugular vein.

PMID- 22144644
TI  - eComment: Cardiac displacement during off-pump coronary artery bypass grafting
      surgery: how much displacement is too much?

PMID- 22144645
TI  - eComment: Pharmacological agents increasing arterial pressure via total
      peripheral vasoconstriction should be avoided for maintaining brain oxygenation
      during cardiac displacement in off-pump cardiac surgery.

PMID- 22144646
TI  - eComment: Postoperative non-invasive assessment of pulmonary vascular resistance
      using Doppler echocardiography.

PMID- 22144647
TI  - eComment: Endothelin-1 correlation with myocardial injury and no-reflow
      phenomenon.

PMID- 22144648
TI  - eComment: Bilateral atrial myxoma.

PMID- 22144649
TI  - eComment: Re: Surgical treatment of primary intracardiac myxoma: 19 years of
      experience.

PMID- 22144650
TI  - eComment: Preserved consciousness in general anesthesia for combined carotid and
      coronary artery bypass grafting surgery.

PMID- 22144651
TI  - eComment: Valve prosthesis-patient mismatch: hemodynamic, echocardiographic and
      clinical consequences.

PMID- 22144652
TI  - eComment: Anticoagulants after atrial fibrillation ablation: the potential use of
      dabigatran.

PMID- 22144653
TI  - eComment: Is it safe to stop anticoagulants after successful surgery for atrial
      fibrillation?

PMID- 22144654
TI  - eComment: Cardiac mesothelial/monocytic incidental excrescence and
      antiphospholipid syndrome.

PMID- 22144655
TI  - eComment: Surgical treatment of coronary arteriovenous fistulas.

PMID- 22144656
TI  - eComment: Cardioplegia in coronary artery fistula to coronary sinus.

PMID- 22144657
TI  - Methylphenidate: established and expanding roles in symptom management.
AB  - Methylphenidate is a psychostimulant originally used for the treatment of
      attention-deficit disorder. Methylphenidate inhibits neuronal neurotransmitter
      transporters involved in the uptake of dopamine and norepinephrine at the level
      of the synapse. Inhibition of these transmitter transporters leads to increased
      concentrations of dopamine and norepinephrine in the synapse, which results in
      increasing alertness. The stimulant effect of methylphenidate has been used for
      the treatment of major depression, poststroke depression, cognitive enhancement
      in patients with brain tumors, neurodegenerative disorders, HIV disease, fatigue,
      and as a treatment for delirium and sedation associated with opioid use. Other
      areas where methylphenidate has been evaluated include gait disorders in the
      elderly individuals and the treatment of apathy in dementia. Analgesic effects
      have been demonstrated in preclinical models but true analgesic effects remain to
      be proven in humans. This article reviews the current use of methylphenidate for
      symptom management with a critical look at the evidence base for its efficacy in
      the conditions described.

PMID- 22144658
TI  - Assessing the readiness of hospice volunteers to utilize technology.
AB  - Although hospice volunteer programs contribute to patient care, little is known
      about their utilization and adaptation of technology. A survey was posted to the
      Hospice Volunteer Association Web site to assess technology use among volunteer
      coordinators and volunteers. Results revealed that participants have access to
      computers, Internet, and e-mail at the hospice agency and routinely use cellular
      phones and e-mail. Despite the use of technology, communication problems with
      volunteers hindered the coordinator's ability to manage scheduling, training, and
      volunteer assignments for patient care. Coordinators and volunteers felt
      comfortable utilizing technology but were less comfortable using technology in
      the patients' home. Several areas are identified for development and integration
      of advanced technology in volunteer programs. Future research is needed to ease
      technology implementation and increase volunteer acceptance.

PMID- 22144659
TI  - Views of hospice and palliative care among younger and older sexually diverse
      women.
AB  - The aim of the present study was to explore end-of-life health care attitudes
      among younger and older sexually diverse women. Self-identified lesbian and
      heterosexual older women as well as lesbian and heterosexual middle-aged women
      were recruited. Results indicated that lesbian women held significantly more
      positive beliefs about hospice services and the role of alternative medicines in
      health care. No differences among sexual orientation were found for comfort
      discussing pain management but heterosexual women reported a significantly
      greater desire for life-sustaining treatments in the event of an incurable
      disease and severe life-limiting conditions (eg, feeding tube, life support, no
      brain response). Additionally, as expected, older women in this study held more
      positive beliefs about hospice and more comfort discussing pain management than
      middle-aged women.

PMID- 22144660
TI  - Music therapy in pediatric palliative care: family-centered care to enhance
      quality of life.
AB  - Research into the value of music therapy in pediatric palliative care (PPC) has
      identified quality of life as one area of improvement for families caring for a
      child in the terminal stages of a life-threatening illness. This small-scale
      investigation collected data in a multisite, international study including
      Minnesota, USA, and Melbourne, Australia. An exploratory mixed method design used
      the qualitative data collected through interviews with parents to interpret
      results from the PedsQL Family Impact Module of overall parental quality of life.
      Parents described music therapy as resulting in physical improvements of their
      child by providing comfort and stimulation. They also valued the positive
      experiences shared by the family in music therapy sessions that were strength
      oriented and family centered. This highlighted the physical and communication
      scales within the PedsQL Family Impact Module, where minimal improvements were
      achieved in contrast to some strong results suggesting diminished quality of life
      in cognitive and daily activity domains. Despite the significant challenges faced
      by parents during this difficult time, parents described many positive
      experiences in music therapy, and the overall score for half of the parents in
      the study did not diminish. The value of music therapy as a service that
      addresses the family-centered agenda of PPC is endorsed by this study.

PMID- 22144661
TI  - Difficult cases of pain and nonpain symptoms in intractable spinal infections: a
      case series.
AB  - In the modern age of advanced surgical techniques and pharmacologic management,
      bacterial spinal infections (SIs) can be managed (either eradicated or
      suppressed) in many hosts. However, the optimal management of SIs may be limited
      by patient comorbidities, which do not allow for surgical management, or limited
      by antimicrobial options due to side effects, toxicities, or emerging drug
      resistance. In these settings, frank and honest discussion regarding risks and
      benefits of treatment should be pursued, including that the SI may be a terminal
      illness. In this case series, we present 3 patients who had bacterial SIs whose
      treatments were limited by the above-mentioned factors. Furthermore, each case
      presented challenges regarding optimal medical management of somatic and
      neuropathic pain associated with the SI.

PMID- 22144662
TI  - Caveolin-1 upregulation contributes to c-Myc-induced high-grade prostatic
      intraepithelial neoplasia and prostate cancer.
AB  - Previously we reported caveolin-1 (Cav-1) overexpression in prostate cancer cells
      and showed that it promotes prostate cancer progression. Here, we report that Cav
      1 was overexpressed in 41.7% (15 of 36) of human high-grade prostatic
      intraepithelial neoplasia (HGPIN) specimens obtained during radical
      prostatectomies. Positive correlations exist between Cav-1-positive (Cav-1(+))
      HGPIN and Cav-1(+) primary prostate cancer (rho = 0.655, P < 0.0001) and between
      Cav-1 and c-Myc expression in HGPIN (rho = 0.41, P = 0.032). To determine whether
      Cav-1 cooperates with c-Myc in development of premalignant lesions and prostate
      cancer in vivo, we generated transgenic mice with c-Myc overexpression driven by
      the ARR(2)PB promoter. In this ARR(2)PB-c-myc model, Cav-1 overexpression was
      found in mouse PIN (mPIN) lesions and prostate cancer cells and was associated
      with a significantly higher ratio of proliferative to apoptotic labeling in mPIN
      lesions than in the Cav-1-negative epithelia adjacent to those lesions (10.02 vs.
      4.34; P = 0.007). Cav-1 overexpression was also associated with increased levels
      of P-Akt and VEGF-A, which were previously associated with Cav-1-induced prostate
      cancer cell survival and positive feedback regulation of cellular Cav-1 levels,
      respectively. In multiple prostate cancer cell lines, Cav-1 protein (but not
      mRNA) was induced by c-Myc transfection, whereas VEGF siRNA transfection
      abrogated c-Myc-induced Cav-1 overexpression, suggesting a c-Myc-VEGF-Cav-1
      signaling axis. Overall, our results suggest that Cav-1 is associated with c-Myc
      in the development of HGPIN and prostate cancer. Furthermore, Cav-1
      overexpression in HGPIN is potentially a biomarker for early identification of
      patients who tend to develop Cav-1(+) primary prostate cancer.

PMID- 22144663
TI  - Assessing adherence to guidelines for common mental disorders in routine clinical
      practice.
AB  - OBJECTIVE: To measure the overall level of adherence to clinical guidelines with
      a set of cross-diagnostic process indicators in a randomly selected sample of
      outpatients who started an acute phase treatment for a common mental disorder in
      a routine clinical setting. DESIGN:  SETTING AND PARTICIPANTS: We developed a
      generic set of quality measures to asses the implementation of guidelines in
      daily practice. This set was tested in a retrospective cohort study in a randomly
      selected sample of 300 outpatients who started an acute phase psychiatric
      treatment for various psychiatric disorders. Patients were treated with
      pharmacotherapy, psychotherapy or a combination of both. MAIN OUTCOME MEASURE:
      Scores on cross-diagnostic process indicators. RESULTS: Most indicators were
      positive in a high to very high percentage, indicating that most treatment
      elements in this routine clinical practice setting were delivered according to
      the guidelines for the acute treatment phase. We observed significant lower
      scores in the combined treatment group as compared with the two other treatment
      groups on the indicators 'correct treatment module' and 'stepped care' (P <=
      0.005). Patients receiving psychotherapy had the best results on the separate
      indicators. Overall, only a minority of the patients in this sample was treated
      in complete accordance with the guidelines and treatment manuals. CONCLUSIONS:
      Assessment of guideline adherence is feasible with this cross-diagnostic set of
      process indicators and hampering factors of implementation could be easily
      detected. Future research should focus on the relationship with treatment
      outcomes.

PMID- 22144664
TI  - MEK1/2 inhibitor selumetinib (AZD6244) inhibits growth of ovarian clear cell
      carcinoma in a PEA-15-dependent manner in a mouse xenograft model.
AB  - Clear cell carcinoma (CCC) of the ovary tends to show resistance to standard
      chemotherapy, which results in poor survival for patients with CCC. Developing a
      novel therapeutic strategy is imperative to improve patient prognosis. Epidermal
      growth factor receptor (EGFR) is frequently expressed in epithelial ovarian
      cancer. One of the major downstream targets of the EGFR signaling cascade is
      extracellular signal-related kinase (ERK). PEA-15, a 15-kDa phosphoprotein, can
      sequester ERK in the cytoplasm. MEK1/2 plays a central role in integrating
      mitogenic signals into the ERK pathway. We tested the hypothesis that inhibition
      of the EGFR-ERK pathway suppresses tumorigenicity in CCC, and we investigated the
      role of PEA-15 in ERK-targeted therapy in CCC. We screened a panel of 4 CCC cell
      lines (RMG-I, SMOV-2, OVTOKO, and KOC-7c) and observed that the EGFR tyrosine
      kinase inhibitor erlotinib inhibited cell proliferation of EGFR-overexpressing
      CCC cell lines through partial dependence on the MEK/ERK pathway. Furthermore,
      erlotinib-sensitive cell lines were also sensitive to the MEK inhibitor
      selumetinib (AZD6244), which is under clinical development. Knockdown of PEA-15
      expression resulted in reversal of selumetinib-sensitive cells to resistant
      cells, implying that PEA-15 contributes to selumetinib sensitivity. Both
      selumetinib and erlotinib significantly suppressed tumor growth (P < 0.0001) in a
      CCC xenograft model. However, selumetinib was better tolerated; erlotinib-treated
      mice exhibited significant toxic effects (marked weight loss and severe skin
      peeling) at high doses. Our findings indicate that the MEK-ERK pathway is a
      potential target for EGFR-overexpressing CCC and indicate that selumetinib and
      erlotinib are worth exploring as therapeutic agents for CCC.

PMID- 22144665
TI  - Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent
      antitumor activity and a superior safety profile for cancer therapy.
AB  - Targeted inhibition of the molecular chaperone Hsp90 results in the simultaneous
      blockade of multiple oncogenic signaling pathways and has, thus, emerged as an
      attractive strategy for the development of novel cancer therapeutics. Ganetespib
      (formerly known as STA-9090) is a unique resorcinolic triazolone inhibitor of
      Hsp90 that is currently in clinical trials for a number of human cancers. In the
      present study, we showed that ganetespib exhibits potent in vitro cytotoxicity in
      a range of solid and hematologic tumor cell lines, including those that express
      mutated kinases that confer resistance to small-molecule tyrosine kinase
      inhibitors. Ganetespib treatment rapidly induced the degradation of known Hsp90
      client proteins, displayed superior potency to the ansamycin inhibitor 17
      allylamino-17-demethoxygeldanamycin (17-AAG), and exhibited sustained activity
      even with short exposure times. In vivo, ganetespib showed potent antitumor
      efficacy in solid and hematologic xenograft models of oncogene addiction, as
      evidenced by significant growth inhibition and/or regressions. Notably,
      evaluation of the microregional activity of ganetespib in tumor xenografts showed
      that ganetespib was efficiently distributed throughout tumor tissue, including
      hypoxic regions >150 MUm from the microvasculature, to inhibit proliferation and
      induce apoptosis. Importantly, ganetespib showed no evidence of cardiac or liver
      toxicity. Taken together, this preclinical activity profile indicates that
      ganetespib may have broad application for a variety of human malignancies, and
      with select mechanistic and safety advantages over other first- and second
      generation Hsp90 inhibitors.

PMID- 22144666
TI  - Prognostic significance of prevalent and incident atrial fibrillation among
      patients hospitalized with acute coronary syndrome: findings from the Gulf RACE-2
      Registry.
AB  - There is a paucity of data on atrial fibrillation (AF) complicating acute
      coronary syndrome (ACS) in Arabian Gulf countries. Thus, we assessed the
      incidence of AF in patients with ACS in these countries and examined the
      associated in-hospital, 30-day, and 1-year adverse outcomes. The population
      comprised 7930 patients enrolled in the second Gulf Registry of Acute Coronary
      Events (Gulf RACE-2). Of 7930 patients with ACS, 217 (2.7%) had AF. Compared with
      patients without AF, patients with AF were less likely to be male (65.9 vs 79.1%)
      and were older (mean age 64.6 vs 56.6 years). Compared with patients without AF,
      in-hospital, 30-day, and 1-year mortality were significantly higher in patients
      with any AF (odds ratio [OR]: 2.7, 2.2, 1.9, respectively; P < .001) and in
      patients with new-onset AF (OR: 5.2, 3.9, 3.1, respectively; P < .001. In
      conclusion, AF in patients with ACS was associated with significantly higher
      short- and long-term mortality.

PMID- 22144667
TI  - Elevated resting heart rate is associated with white blood cell count in middle
      aged and elderly individuals without apparent cardiovascular disease.
AB  - We investigated the association between resting heart rate (HR) and inflammation
      markers in a healthy population. White blood cell (WBC) count was used as a
      surrogate marker of subclinical inflammation. Smoking status, body mass index,
      resting HR, high-density lipoprotein cholesterol, triglycerides, uric acid, and
      glycated hemoglobin were significantly associated with WBC in both men and women.
      Blood pressure and fasting plasma glucose levels, however, were associated with
      WBC only in women. Logistic regression analysis indicated that for every 10 beats
      per minute increase in HR, the odds ratio of an increase in the WBC was
      approximately 1.3 in both men and women. These findings indicate the clinical
      significance of resting HR for identifying individuals at risk of subclinical
      inflammation and a future cardiovascular event.

PMID- 22144668
TI  - Antiplatelet efficacy of long-term treatment with clopidogrel besylate in
      patients with a history of acute coronary syndrome: comparison with clopidogrel
      hydrogen sulfate.
AB  - The efficacy of clopidogrel therapy in patients with an acute coronary syndrome
      (ACS) has been established using the clopidogrel hydrogen sulfate (CHS)
      formulation. We compared the antiplatelet effectiveness of long-term
      administration of the original CHS with a generic clopidogrel besylate (CB) salt
      formulation in 86 patients with a history of an ACS. At 1 month after the
      episode, patients receiving 75 mg/d CHS were randomized to continue with CHS (n =
      41) or to switch to 75 mg/d CB (n = 45). Platelet aggregation, vasodilator
      stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression, and
      platelet-leucocyte conjugates were determined before randomization and at 6
      months afterward. No difference in any platelet parameter studied was observed
      between the 2 groups either before randomization or after 6 months of treatment
      with CHS or CB. We conclude that there is no difference in the antiplatelet
      efficacy between CB and CHS during long-term administration in patients with a
      history of an ACS.

PMID- 22144669
TI  - Adherence to the mediterranean diet in relation to ischemic stroke nonfatal
      events in nonhypercholesterolemic and hypercholesterolemic participants: results
      of a case/case-control study.
AB  - The aim of the present work was to evaluate the association between adherence to
      the Mediterranean diet and the development of ischemic stroke according to
      cholesterol levels. During 2009-2010, 500 participants were enrolled; 250 were
      consecutive patients (77 +/- 9 years, 55.6% men) with a first ischemic stroke and
      250 population-based, control participants, matched to the patients by age and
      sex. Sociodemographic, clinical, dietary, and other lifestyle characteristics
      were measured. Adherence to the Mediterranean diet was assessed by the validated
      MedDietScore (theoretical range: 0-55). After various adjustments, each 1/55 unit
      increase in the MedDietScore was associated with 17% lower likelihood of having
      an ischemic stroke in nonhypercholesterolemic participants (95%CI: 0.72-0.96) and
      10% lower likelihood in participants with hypercholesterolemia (95%CI: 0.81
      0.99). The present work highlights the cardioprotective benefits from the
      adoption of the Mediterranean diet, by showing its beneficial effect regarding
      ischemic stroke development, regardless of the presence of hypercholesterolemia.

PMID- 22144670
TI  - Signaling cascades for delta-opioid receptor-mediated inhibition of GABA synaptic
      transmission and behavioral antinociception.
AB  - Membrane trafficking of the delta-opioid receptor (DOR) from intracellular
      compartments to plasma membrane in central neurons, induced by various
      pathological conditions such as long-term opioid exposure, represents unique
      receptor plasticity involved in the mechanisms of long-term opioid effects in
      opioid addiction and opioid treatment of chronic pain. However, the signaling
      pathways coupled to the newly emerged functional DOR in central neurons are
      largely unknown at present. In this study, we investigated the signaling cascades
      of long-term morphine-induced DOR for its cellular and behavioral effects in
      neurons of the rat brainstem nucleus raphe magnus (NRM), a key supraspinal site
      for opioid analgesia. We found that, among the three phospholipase A(2) (PLA(2))
      regulated arachidonic acid (AA) metabolic pathways of lipoxygenase,
      cyclooxygenase, and epoxygenase, 12-lipoxygenase of the lipoxygenase pathway
      primarily mediated DOR inhibition of GABA synaptic transmission, because
      inhibitors of 12-lipoxygenase as well as lipoxygenases and PLA(2) largely blocked
      the DOR- or AA-induced GABA inhibition in NRM neurons in brainstem slices in
      vitro. Blockade of the epoxygenase pathway was ineffective, whereas blocking
      either 5-lipoxygenase of the lipoxygenase pathway or the cyclooxygenase pathway
      enhanced the DOR-mediated GABA inhibition. Behaviorally in rats in vivo, NRM
      infusion of 12-lipoxygenase inhibitors significantly reduced DOR-induced
      antinociceptive effect whereas inhibitors of 5-lipoxygenase and cyclooxygenase
      augmented the DOR antinociception. These findings suggest the PLA(2)-AA-12
      lipoxygenase pathway as a primary signaling cascade for DOR-mediated analgesia
      through inhibition of GABA neurotransmission and indicate potential therapeutic
      benefits of combining 5-lipoxygenase and cyclooxygenase inhibitors for maximal
      pain inhibition.

PMID- 22144671
TI  - Heteromeric canonical transient receptor potential 1 and 4 channels play a
      critical role in epileptiform burst firing and seizure-induced neurodegeneration.
AB  - Canonical transient receptor potential channels (TRPCs) are receptor-operated
      cation channels that are activated in response to phospholipase C signaling.
      Although TRPC1 is ubiquitously expressed in the brain, TRPC4 expression is the
      most restrictive, with the highest expression level limited to the lateral
      septum. The subunit composition of neuronal TRPC channels remains uncertain
      because of conflicting data from recombinant expression systems. Here we report
      that the large depolarizing plateau potential that underlies the epileptiform
      burst firing induced by metabotropic glutamate receptor agonists in lateral
      septal neurons was completely abolished in TRPC1/4 double-knockout mice, and was
      abolished in 74% of lateral septal neurons in TRPC1 knockout mice. Furthermore,
      neuronal cell death in the lateral septum and the cornu ammonis 1 region of
      hippocampus after pilocarpine-induced severe seizures was significantly
      ameliorated in TRPC1/4 double-knockout mice. Our data suggest that both TRPC1 and
      TRPC4 are essential for an intrinsic membrane conductance mediating the plateau
      potential in lateral septal neurons, possibly as heteromeric channels. Moreover,
      excitotoxic neuronal cell death, an underlying process for many neurological
      diseases, is not mediated merely by ionotropic glutamate receptors but also by
      heteromeric TRPC channels activated by metabotropic glutamate receptors. TRPC
      channels could be an unsuspected but critical molecular target for clinical
      intervention for excitotoxicity.

PMID- 22144672
TI  - V2 vasopressin receptor (V2R) mutations in partial nephrogenic diabetes insipidus
      highlight protean agonism of V2R antagonists.
AB  - Inactivating mutations of the V2 vasopressin receptor (V2R) cause cross-linked
      congenital nephrogenic diabetes insipidus (NDI), resulting in renal resistance to
      the antidiuretic hormone AVP. In two families showing partial NDI, characterized
      by an apparently normal response to diagnostic tests and an increase in the basal
      ADH levels suggesting AVP resistance, we have identified two V2R mutations, Ser
      333del and Y128S. Both mutant V2Rs, when expressed in COS-7 cells, show partial
      defects in vasopressin-stimulated cAMP accumulation and intracellular
      localization. The inhibition of internalization does not rescue their
      localization. In contrast, the non-peptide V2R antagonists OPC41061 and OPC31260
      partially rescue the membrane localization and basal function of these V2R
      mutants, whereas they inhibit the basal activity of the wild-type V2R. These
      results indicate that a partial loss of function of Ser-333del and Y128S mutant
      V2Rs results from defective membrane trafficking. These findings further indicate
      that V2R antagonists can act as protean agonists, serving as pharmacological
      chaperones for inactivating V2R mutants and also as inverse agonists of wild-type
      receptors. We speculate that this protean agonism could underlie the possible
      dual beneficial effects of the V2R antagonist: improvement of hyponatremia with
      heart failure or polycystic kidney disease and potential rescue of NDI.

PMID- 22144673
TI  - Acyl chain specificity of ceramide synthases is determined within a region of 150
      residues in the Tram-Lag-CLN8 (TLC) domain.
AB  - In mammals, ceramides are synthesized by a family of six ceramide synthases
      (CerS), transmembrane proteins located in the endoplasmic reticulum, where each
      use fatty acyl-CoAs of defined chain length for ceramide synthesis. Little is
      known about the molecular features of the CerS that determine acyl-CoA
      selectivity. We now explore CerS structure-function relationships by constructing
      chimeric proteins combining sequences from CerS2, which uses C22-CoA for ceramide
      synthesis, and CerS5, which uses C16-CoA. CerS2 and -5 are 41% identical and 63%
      similar. Chimeras containing approximately half of CerS5 (from the N terminus)
      and half of CerS2 (from the C terminus) were catalytically inactive. However, the
      first 158 residues of CerS5 could be replaced with the equivalent region of CerS2
      without affecting specificity of CerS5 toward C16-CoA; likewise, the putative
      sixth transmembrane domain (at the C terminus) of CerS5 could be replaced with
      the corresponding sequence of CerS2 without affecting CerS5 specificity.
      Remarkably, a chimeric CerS5/2 protein containing the first 158 residues and the
      last 83 residues of CerS2 displayed specificity toward C16-CoA, and a chimeric
      CerS2/5 protein containing the first 150 residues and the last 79 residues of
      CerS5 displayed specificity toward C22-CoA, demonstrating that a minimal region
      of 150 residues is sufficient for retaining CerS specificity.

PMID- 22144674
TI  - Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP): a new
      player in cell signaling.
AB  - Precise balance between phosphorylation, catalyzed by protein kinases, and
      dephosphorylation, catalyzed by protein phosphatases, is essential for cellular
      homeostasis. Deregulation of this balance leads to pathophysiological states that
      drive diseases such as cancer, heart disease, and diabetes. The recent discovery
      of the PHLPP (pleckstrin homology domain leucine-rich repeat protein phosphatase)
      family of Ser/Thr phosphatases adds a new player to the cast of phosphate
      controlling enzymes in cell signaling. PHLPP isozymes catalyze the
      dephosphorylation of a conserved regulatory motif, the hydrophobic motif, on the
      AGC kinases Akt, PKC, and S6 kinase, as well as an inhibitory site on the kinase
      Mst1, to inhibit cellular proliferation and induce apoptosis. The frequent
      deletion of PHLPP in cancer, coupled with the development of prostate tumors in
      mice lacking PHLPP1, identifies PHLPP as a novel tumor suppressor. This
      minireview discusses the structure, function, and regulation of PHLPP, with
      particular focus on its role in disease.

PMID- 22144675
TI  - Amyloid precursor protein revisited: neuron-specific expression and highly stable
      nature of soluble derivatives.
AB  - APP processing and amyloid-beta production play a central role in Alzheimer
      disease pathogenesis. APP has been considered a ubiquitously expressed protein.
      In addition to amyloid-beta, alpha- or beta-secretase-dependent cleavage of APP
      also generates soluble secreted APP (APPsalpha or APPsbeta, respectively).
      Interestingly, APPsbeta has been shown to be subject to further cleavage to
      create an N-APP fragment that binds to the DR6 death receptor and mediates axon
      pruning and degeneration under trophic factor withdrawal conditions. By
      performing APP immunocytochemical staining, we found that, unexpectedly, many
      antibodies yielded nonspecific staining in APP-null samples. Screening of a
      series of antibodies allowed us to identify a rabbit monoclonal antibody Y188
      that is highly specific for APP and prompted us to re-examine the expression,
      localization, and stability of endogenous APP and APPsbeta in wild-type and in
      APPsbeta knock-in mice, respectively. In contrast to earlier studies, we found
      that APP is specifically expressed in neurons and that its expression cannot be
      detected in major types of glial cells under basal or neuroinflammatory
      conditions. Both APPsalpha and APPsbeta are highly stable in the central nervous
      system (CNS) and do not undergo further cleavage with or without trophic factor
      support. Our results clarify several key questions with regard to the fundamental
      properties of APP and offer critical cellular insights into the pathophysiology
      of APP.

PMID- 22144676
TI  - BMPER protein is a negative regulator of hepcidin and is up-regulated in
      hypotransferrinemic mice.
AB  - The BMP/SMAD4 pathway has major effects on liver hepcidin levels. Bone
      morphogenetic protein-binding endothelial cell precursor-derived regulator
      (Bmper), a known regulator of BMP signaling, was found to be overexpressed at the
      mRNA and protein levels in liver of genetically hypotransferrinemic mice
      (Trf(hpx/hpx)). Soluble BMPER peptide inhibited BMP2- and BMP6-dependent hepcidin
      promoter activity in both HepG2 and HuH7 cells. These effects correlated with
      reduced cellular levels of pSMAD1/5/8. Addition of BMPER peptide to primary human
      hepatocytes abolished the BMP2-dependent increase in hepcidin mRNA, whereas
      injection of Bmper peptide into mice resulted in reduced liver hepcidin and
      increased serum iron levels. Thus Bmper may play an important role in suppressing
      hepcidin production in hypotransferrinemic mice.

PMID- 22144677
TI  - Glucose and insulin induction of bile acid synthesis: mechanisms and implication
      in diabetes and obesity.
AB  - Bile acids facilitate postprandial absorption of nutrients. Bile acids also
      activate the farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5
      and play a major role in regulating lipid, glucose, and energy metabolism.
      Transgenic expression of cholesterol 7alpha-hydroxylase (CYP7A1) prevented high
      fat diet-induced diabetes and obesity in mice. In this study, we investigated the
      nutrient effects on bile acid synthesis. Refeeding of a chow diet to fasted mice
      increased CYP7A1 expression, bile acid pool size, and serum bile acids in wild
      type and humanized CYP7A1-transgenic mice. Chromatin immunoprecipitation assays
      showed that glucose increased histone acetylation and decreased histone
      methylation on the CYP7A1 gene promoter. Refeeding also induced CYP7A1 in fxr
      deficient mice, indicating that FXR signaling did not play a role in postprandial
      regulation of bile acid synthesis. In streptozocin-induced type I diabetic mice
      and genetically obese type II diabetic ob/ob mice, hyperglycemia increased
      histone acetylation status on the CYP7A1 gene promoter, leading to elevated basal
      Cyp7a1 expression and an enlarged bile acid pool with altered bile acid
      composition. However, refeeding did not further increase CYP7A1 expression in
      diabetic mice. In summary, this study demonstrates that glucose and insulin are
      major postprandial factors that induce CYP7A1 gene expression and bile acid
      synthesis. Glucose induces CYP7A1 gene expression mainly by epigenetic
      mechanisms. In diabetic mice, CYP7A1 chromatin is hyperacetylated, and fasting to
      refeeding response is impaired and may exacerbate metabolic disorders in
      diabetes.

PMID- 22144678
TI  - Control of type I interferon-induced cell death by Orai1-mediated calcium entry
      in T cells.
AB  - Store-operated Ca(2+) entry (SOCE) is an essential process in T cell activation.
      SOCE is controlled by the Ca(2+) release-activated Ca(2+) (CRAC) channel encoded
      by the gene Orai1 that is expressed on the plasma membrane and activated by STIM1
      when ER Ca(2+) stores are depleted. Our earlier work showed that a somatic T-cell
      line Jurkat mutant H123 bearing a defect in Ca(2+) signaling was susceptible to
      the apoptotic effects of type I interferons (IFN-alpha/beta). The nature of the
      mutation and whether this mutation was linked to IFN-alpha/beta apoptotic
      susceptibility was unknown. Here we show that H123 cells lacked Orai1 and exhibit
      reduced STIM1 protein. Reconstitution of both Orai1 and STIM1 in H123 cells
      rescued SOCE in response to thapsigargin and ionomycin and abrogated IFN
      alpha/beta-induced apoptosis. Reciprocally, overexpression of the dominant
      negative Orai1-E106A in either parental Jurkat cells or an unrelated human T cell
      line (CEM391) inhibited SOCE and led to sensitization to IFN-alpha/beta-induced
      apoptosis. Furthermore, we showed that the Ca(2+) response pathway antagonized
      the IFN-alpha/beta -induced transcriptional responses; in the absence of SOCE,
      this negative regulatory effect was lost. However, the inhibitory effect of
      Ca(2+) on type I IFN-induced gene transcription was diminished by pharmacological
      inhibition of NF-kappaB in cells with intact SOCE. Our findings reveal an
      unexpected and novel regulatory crosstalk mechanism between type I IFNs and store
      operated Ca(2+) signaling pathways mediated at least in part by NF-kappaB
      activity with significant clinical implications to both viral and tumor
      immunology.

PMID- 22144679
TI  - Exometabolome analysis identifies pyruvate dehydrogenase as a target for the
      antibiotic triphenylbismuthdichloride in multiresistant bacterial pathogens.
AB  - The desperate need for new therapeutics against notoriously antibiotic-resistant
      bacteria has led to a quest for novel antibacterial target structures and
      compounds. Moreover, defining targets and modes of action of new antimicrobial
      compounds remains a major challenge with standard technologies. Here we
      characterize the antibacterial properties of triphenylbismuthdichloride (TPBC),
      which has recently been successfully used against device-associated infections.
      We demonstrate that TPBC has potent antimicrobial activity against many bacterial
      pathogens. Using an exometabolome profiling approach, a unique TPBC-mediated
      change in the metabolites of Staphylococcus aureus was identified, indicating
      that TPBC blocks bacterial pyruvate catabolism. Enzymatic studies showed that
      TPBC is a highly efficient, uncompetitive inhibitor of the bacterial pyruvate
      dehydrogenase complex. Our study demonstrates that metabolomics approaches can
      offer new avenues for studying the modes of action of antimicrobial compounds,
      and it indicates that inhibition of the bacterial pyruvate dehydrogenase complex
      may represent a promising strategy for combating multidrug-resistant bacteria.

PMID- 22144680
TI  - Suppression of Galphas synthesis by simvastatin treatment of vascular endothelial
      cells.
AB  - These studies explore the effects of statins on cyclic AMP-modulated signaling
      pathways in vascular endothelial cells. We previously observed (Kou, R.,
      Sartoretto, J., and Michel, T. (2009) J. Biol. Chem. 284, 14734-14743) that
      simvastatin treatment of endothelial cells leads to a marked decrease in PKA
      modulated phosphorylation of the protein VASP. Here we show that long-term
      treatment of mice with simvastatin attenuates the vasorelaxation response to the
      beta-adrenergic agonist isoproterenol, without affecting endothelin-induced
      vasoconstriction or carbachol-induced vasorelaxation. We found that statin
      treatment of endothelial cells dose-dependently inhibits PKA activation as
      assessed by analyses of serine 157 VASP phosphorylation as well as Epac-mediated
      Rap1 activation. These effects of simvastatin are completely reversed by
      mevalonate and by geranylgeranyl pyrophosphate, implicating geranylgeranylation
      as a critical determinant of the stain response. We used biochemical approaches
      as well as fluorescence resonance energy transfer (FRET) methods with a cAMP
      biosensor to show that simvastatin treatment of endothelial cells markedly
      inhibits cAMP accumulation in response to epinephrine. Importantly, simvastatin
      treatment significantly decreases Galpha(s) abundance, without affecting other
      Galpha subunits. Simvastatin treatment does not influence Galpha(s) protein
      stability, and paradoxically increases the abundance of Galpha(s) mRNA. Finally,
      we found that simvastatin treatment inhibits Galpha(s) translation mediated by
      Akt/mTOR/eIF4/4EBP. Taken together, these findings establish a novel mechanism by
      which simvastatin modulates beta-adrenergic signaling in vascular wall, and may
      have implications for cardiovascular therapeutics.

PMID- 22144681
TI  - Functional impact of heterogeneous nuclear ribonucleoprotein A2/B1 in smooth
      muscle differentiation from stem cells and embryonic arteriogenesis.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) play various roles in
      transcriptional and post-transcriptional modulation of gene expression. However,
      it remains unclear if hnRNPs are associated with smooth muscle cell (SMC)
      differentiation from stem cells and embryonic arteriogenesis. In this study,
      mouse embryonic stem (ES) cells were cultivated on collagen IV-coated plates and
      smooth muscle differentiation medium. We found that hnRNPA2/B1 gene and protein
      expression was significantly up-regulated following 3-7 days of cell
      differentiation. hnRNPA2/B1 knockdown resulted in down-regulation of specific
      smooth muscle markers and transcription factors, whereas enforced expression of
      hnRNPA2/B1 enhanced the expression of these genes. Moreover, we demonstrated by
      using luciferase and chromatin immunoprecipitation assays that hnRNPA2/B1 could
      transcriptionally regulate SMC gene expression through direct binding to
      promoters of Smalphaa and Sm22alpha genes. We further demonstrated that chromobox
      protein homolog gene 3, a previously identified SMC differentiation regulatory
      nuclear protein, is required for hnRNPA2/B1-mediated SMC differentiation gene
      expression. Importantly, specifically designed Hnrnpa2/b1 morpholinos for in vivo
      knockdown could inhibit the migration and differentiation of neural crest cells
      into SMCs in chick embryos. This resulted in the maldevelopment of branchial arch
      arteries and increased embryo lethality at a later developmental stage. Our
      findings demonstrated that hnRNPA2/B1 plays a functional role in SMC
      differentiation from stem cells in vitro and embryonic branchial arch artery
      development. This indicates that hnRNPA2/B1 is a potential modulating target for
      deriving SMCs from stem cells and cardiovascular regenerative medicine.

PMID- 22144683
TI  - Making your database available through Wikipedia: the pros and cons.
AB  - Wikipedia, the online encyclopedia, is the most famous wiki in use today. It
      contains over 3.7 million pages of content; with many pages written on scientific
      subject matters that include peer-reviewed citations, yet are written in an
      accessible manner and generally reflect the consensus opinion of the community.
      In this, the 19th Annual Database Issue of Nucleic Acids Research, there are 11
      articles that describe the use of a wiki in relation to a biological database. In
      this commentary, we discuss how biological databases can be integrated with
      Wikipedia, thereby utilising the pre-existing infrastructure, tools and above
      all, large community of authors (or Wikipedians). The limitations to the content
      that can be included in Wikipedia are highlighted, with examples drawn from
      articles found in this issue and other wiki-based resources, indicating why other
      wiki solutions are necessary. We discuss the merits of using open wikis, like
      Wikipedia, versus other models, with particular reference to potential vandalism.
      Finally, we raise the question about the future role of dedicated database
      biocurators in context of the thousands of crowdsourced, community annotations
      that are now being stored in wikis.

PMID- 22144682
TI  - Zinc finger protein ZFP57 requires its co-factor to recruit DNA
      methyltransferases and maintains DNA methylation imprint in embryonic stem cells
      via its transcriptional repression domain.
AB  - Previously, we discovered that ZFP57 is a maternal-zygotic effect gene, and it
      maintains DNA methylation genomic imprint at multiple imprinted regions in mouse
      embryos. Despite these findings, it remains elusive how DNA methyltransferases
      are targeted to the imprinting control regions to initiate and maintain DNA
      methylation imprint. To gain insights into these essential processes in genomic
      imprinting, we examined how ZFP57 maintains genomic DNA methylation imprint in
      mouse embryonic stem (ES) cells. Here we demonstrate that the loss of ZFP57 in
      mouse ES cells led to a complete loss of genomic DNA methylation imprint at
      multiple imprinted regions, similar to its role in mouse embryos. However,
      reintroduction of ZFP57 into Zfp57-null ES cells did not result in reacquisition
      of DNA methylation imprint, suggesting that the memory for genomic imprinting had
      been lost or altered in Zfp57-null ES cells in culture. Interestingly, ZFP57 and
      DNA methyltransferases could form complexes in the presence of
      KAP1/TRIM28/TIF1beta when co-expressed in COS cells. We also found that the wild
      type exogenous ZFP57 but not the mutant ZFP57 lacking the KRAB box that interacts
      with its co-factor KAP1/TRIM28/TIF1beta could substitute for the endogenous ZFP57
      in maintaining the DNA methylation imprint in ES cells. These results suggest
      that ZFP57 may recruit DNA methyltransferases to its target regions to maintain
      DNA methylation imprint, and this interaction is likely facilitated by
      KAP1/TRIM28/TIF1beta.

PMID- 22144685
TI  - The 2012 Nucleic Acids Research Database Issue and the online Molecular Biology
      Database Collection.
AB  - The 19th annual Database Issue of Nucleic Acids Research features descriptions of
      92 new online databases covering various areas of molecular biology and 100
      papers describing recent updates to the databases previously described in NAR and
      other journals. The highlights of this issue include, among others, a description
      of neXtProt, a knowledgebase on human proteins; a detailed explanation of the
      principles behind the NCBI Taxonomy Database; NCBI and EBI papers on the recently
      launched BioSample databases that store sample information for a variety of
      database resources; descriptions of the recent developments in the Gene Ontology
      and UniProt Gene Ontology Annotation projects; updates on Pfam, SMART and
      InterPro domain databases; update papers on KEGG and TAIR, two universally
      acclaimed databases that face an uncertain future; and a separate section with 10
      wiki-based databases, introduced in an accompanying editorial. The NAR online
      Molecular Biology Database Collection, available at
      http://www.oxfordjournals.org/nar/database/a/, has been updated and now lists
      1380 databases. Brief machine-readable descriptions of the databases featured in
      this issue, according to the BioDBcore standards, will be provided at the
      http://biosharing.org/biodbcore web site. The full content of the Database Issue
      is freely available online on the Nucleic Acids Research web site
      (http://nar.oxfordjournals.org/).

PMID- 22144684
TI  - Description and analysis of genetic variants in French hereditary breast and
      ovarian cancer families recorded in the UMD-BRCA1/BRCA2 databases.
AB  - BRCA1 and BRCA2 are the two main genes responsible for predisposition to breast
      and ovarian cancers, as a result of protein-inactivating monoallelic mutations.
      It remains to be established whether many of the variants identified in these two
      genes, so-called unclassified/unknown variants (UVs), contribute to the disease
      phenotype or are simply neutral variants (or polymorphisms). Given the clinical
      importance of establishing their status, a nationwide effort to annotate these
      UVs was launched by laboratories belonging to the French GGC consortium (Groupe
      Genetique et Cancer), leading to the creation of the UMD-BRCA1/BRCA2 databases
      (http://www.umd.be/BRCA1/ and http://www.umd.be/BRCA2/). These databases have
      been endorsed by the French National Cancer Institute (INCa) and are designed to
      collect all variants detected in France, whether causal, neutral or UV. They
      differ from other BRCA databases in that they contain co-occurrence data for all
      variants. Using these data, the GGC French consortium has been able to classify
      certain UVs also contained in other databases. In this article, we report some
      novel UVs not contained in the BIC database and explore their impact in cancer
      predisposition based on a structural approach.

PMID- 22144687
TI  - GenBank.
AB  - GenBank(r) is a comprehensive database that contains publicly available
      nucleotide sequences for more than 250,00 formally described species. These
      sequences are obtained primarily through submissions from individual laboratories
      and batch submissions from large-scale sequencing projects, including whole
      genome shotgun (WGS) and environmental sampling projects. Most submissions are
      made using the web-based BankIt or standalone Sequin programs, and accession
      numbers are assigned by GenBank staff upon receipt. Daily data exchange with the
      European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures
      worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval
      system, which integrates data from the major DNA and protein sequence databases
      along with taxonomy, genome, mapping, protein structure and domain information,
      and the biomedical journal literature via PubMed. BLAST provides sequence
      similarity searches of GenBank and other sequence databases. Complete bimonthly
      releases and daily updates of the GenBank database are available by FTP. To
      access GenBank and its related retrieval and analysis services, begin at the NCBI
      home page: www.ncbi.nlm.nih.gov.

PMID- 22144686
TI  - MeCP2 binds to nucleosome free (linker DNA) regions and to H3K9/H3K27 methylated
      nucleosomes in the brain.
AB  - Methyl-CpG-binding protein 2 (MeCP2) is a chromatin-binding protein that mediates
      transcriptional regulation, and is highly abundant in brain. The nature of its
      binding to reconstituted templates has been well characterized in vitro. However,
      its interactions with native chromatin are less understood. Here we show that
      MeCP2 displays a distinct distribution within fractionated chromatin from various
      tissues and cell types. Artificially induced global changes in DNA methylation by
      3-aminobenzamide or 5-aza-2'-deoxycytidine, do not significantly affect the
      distribution or amount of MeCP2 in HeLa S3 or 3T3 cells. Most MeCP2 in brain is
      chromatin-bound and localized within highly nuclease-accessible regions. We also
      show that, while in most tissues and cell lines, MeCP2 forms stable complexes
      with nucleosome, in brain, a fraction of it is loosely bound to chromatin, likely
      to nucleosome-depleted regions. Finally, we provide evidence for novel
      associations of MeCP2 with mononucleosomes containing histone H2A.X, H3K9me(2)
      and H3K27me(3) in different chromatin fractions from brain cortex and in vitro.
      We postulate that the functional compartmentalization and tissue-specific
      distribution of MeCP2 within different chromatin types may be directed by its
      association with nucleosomes containing specific histone variants, and post
      translational modifications.

PMID- 22144688
TI  - Effect of antiplatelet agents, statins, and other drugs on vascular access
      patency rates.

PMID- 22144689
TI  - Thinking beyond traditional cardiovascular risk factors: the role of arterial
      stiffness in targeting residual risk.

PMID- 22144690
TI  - Eph receptor function is modulated by heterooligomerization of A and B type Eph
      receptors.
AB  - Eph receptors interact with ephrin ligands on adjacent cells to facilitate tissue
      patterning during normal and oncogenic development, in which unscheduled
      expression and somatic mutations contribute to tumor progression. EphA and B
      subtypes preferentially bind A- and B-type ephrins, respectively, resulting in
      receptor complexes that propagate via homotypic Eph-Eph interactions. We now show
      that EphA and B receptors cocluster, such that specific ligation of one receptor
      promotes recruitment and cross-activation of the other. Remarkably, coexpression
      of a kinase-inactive mutant EphA3 with wild-type EphB2 can cause either cross
      activation or cross-inhibition, depending on relative expression. Our findings
      indicate that cellular responses to ephrin contact are determined by the
      EphA/EphB receptor profile on a given cell rather than the individual Eph
      subclass. Importantly, they imply that in tumor cells coexpressing different
      Ephs, functional mutations in one subtype may cause phenotypes that are a result
      of altered signaling from heterotypic rather from homotypic Eph clusters.

PMID- 22144691
TI  - Subunit-dependent modulation of septin assembly: budding yeast septin Shs1
      promotes ring and gauze formation.
AB  - Septins are conserved guanosine triphosphate-binding cytoskeletal proteins
      involved in membrane remodeling. In budding yeast, five mitotic septins (Cdc3,
      Cdc10, Cdc11, Cdc12, and Shs1), which are essential for cytokinesis, transition
      during bud growth from a patch to a collar, which splits into two rings in
      cytokinesis and is disassembled before the next cell cycle. Cdc3, Cdc10, Cdc11,
      and Cdc12 form an apolar octameric rod with Cdc11 at each tip, which polymerizes
      into straight paired filaments. We show that Shs1 substitutes for Cdc11,
      resulting in octameric rods that do not polymerize into filaments but associate
      laterally, forming curved bundles that close into rings. In vivo, half of
      shs1Delta mutant cells exhibit incomplete collars and disrupted neck filaments.
      Importantly, different phosphomimetic mutations in Shs1 can either prevent ring
      formation or promote formation of a gauzelike meshwork. These results show that a
      single alternative terminal subunit is sufficient to confer a distinctive higher
      order septin ultrastructure that can be further regulated by phosphorylation.

PMID- 22144692
TI  - Biogenesis of a novel compartment for autophagosome-mediated unconventional
      protein secretion.
AB  - The endoplasmic reticulum (ER)-Golgi-independent, unconventional secretion of
      Acb1 requires many different proteins. They include proteins necessary for the
      formation of autophagosomes, proteins necessary for the fusion of membranes with
      the endosomes, proteins of the multivesicular body pathway, and the cell surface
      target membrane SNARE Sso1, thereby raising the question of what achieves the
      connection between these diverse proteins and Acb1 secretion. In the present
      study, we now report that, upon starvation in Saccharomyces cerevisiae, Grh1 is
      collected into unique membrane structures near Sec13-containing ER exit sites.
      Phosphatidylinositol 3 phosphate, the ESCRT (endosomal sorting complex required
      for transport) protein Vps23, and the autophagy-related proteins Atg8 and Atg9
      are recruited to these Grh1-containing membranes, which lack components of the
      Golgi apparatus and the endosomes, and which we call a novel compartment for
      unconventional protein secretion (CUPS). We describe the cellular proteins
      required for the biogenesis of CUPS, which we believe is the sorting station for
      Acb1's release from the cells.

PMID- 22144693
TI  - Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid
      droplet contact sites.
AB  - Lipid droplets (LDs) are dynamic cellular organelles that control many biological
      processes. However, molecular components determining LD growth are poorly
      understood. Genetic analysis has indicated that Fsp27, an LD-associated protein,
      is important in controlling LD size and lipid storage in adipocytes. In this
      paper, we demonstrate that Fsp27 is focally enriched at the LD-LD contacting site
      (LDCS). Photobleaching revealed the occurrence of lipid exchange between
      contacted LDs in wild-type adipocytes and Fsp27-overexpressing cells but not
      Fsp27-deficient adipocytes. Furthermore, live-cell imaging revealed a unique
      Fsp27-mediated LD growth process involving a directional net lipid transfer from
      the smaller to larger LDs at LDCSs, which is in accordance with the biophysical
      analysis of the internal pressure difference between the contacting LD pair.
      Thus, we have uncovered a novel molecular mechanism of LD growth mediated by
      Fsp27.

PMID- 22144694
TI  - Correlates of mother-to-child transmission of HIV in the United States and Puerto
      Rico.
AB  - OBJECTIVE: The goal of this study was to examine associations between
      demographic, behavioral, and clinical variables and mother-to-child HIV
      transmission in 15 US jurisdictions for birth years 2005 through 2008. METHODS:
      The study used Enhanced Perinatal Surveillance system data for HIV-infected women
      who gave birth to live infants. Multivariable logistic regression was used to
      assess variables associated with mother-to-child transmission. RESULTS: Among
      8054 births, 179 infants (2.2%) were diagnosed with HIV infection. Half of the
      births had at least 1 missed prevention opportunity: 74.3% of infected infants,
      52.1% of uninfected infants. Among 7757 mother-infant pairs with sufficient data
      for analysis, the odds of having an HIV-infected infant were higher for women who
      received late testing or no prenatal antiretroviral medications (odds ratio: 2.5
      [95% confidence interval (CI): 1.5-4.0] and 3.5 [95% CI: 2.0-6.4], respectively).
      The odds for mothers who breastfed were 4.6 times (95% CI: 2.2-9.8) the odds for
      those who did not breastfeed. The adjusted odds for women with CD4 counts <200
      cells per microliter were 2.4 times (95% CI: 1.4-4.2) those for women with CD4
      counts >=500 cells per microliter. The odds for women who abused substances were
      twice (95% CI: 1.4-2.9) those for women who did not. CONCLUSIONS: The odds of
      having an HIV-infected infant were higher among HIV-infected women who were
      tested late, had no antiretroviral medications, abused substances, breastfed, or
      had lower CD4 cell counts. Increases in earlier HIV diagnosis, substance abuse
      treatment, avoidance of breastfeeding, and use of prenatal antiretroviral
      medications are critical in eliminating perinatal HIV infections in the United
      States.

PMID- 22144695
TI  - Childhood cumulative risk and obesity: the mediating role of self-regulatory
      ability.
AB  - OBJECTIVES: We tested whether early childhood risk exposures are related to
      weight gain in adolescence and evaluate an underlying mechanism, self-regulatory
      behavior, for the risk-obesity link. METHODS: Cumulative risk exposure to 9
      sociodemographic (eg, poverty), physical (eg, substandard housing), and
      psychosocial (eg, family turmoil) stressors was assessed in 244 nine-year-old
      children. BMI was calculated at age 9 and then 4 years later. At age 9,
      children's ability to delay gratification as an index of self-regulatory behavior
      was assessed. Path analyses were then estimated to evaluate our mediational model
      (Cumulative risk -> Self-regulation -> BMI) over a 4-year period in a
      prospective, longitudinal design. RESULTS: Nine-year-old children exposed to a
      greater accumulation of multiple risk factors show larger gains in adiposity over
      the next four year period, net of their initial BMI. These gains in BMI during
      early adolescence are largely accounted for by deteriorated self-regulatory
      abilities among children facing more cumulative risks. CONCLUSIONS: Early
      childhood risk exposure leads to larger gains in BMI in adolescence. Given the
      importance of childhood adiposity to the development of obesity later in life,
      understanding the underlying mechanisms that link early experience to weight gain
      is an essential task. Deficiencies in self-regulation in response to chronic
      stress appears to be an important agent in the obesity epidemic.

PMID- 22144696
TI  - Symptoms and time to medical care in children with accidental extremity
      fractures.
AB  - BACKGROUND AND OBJECTIVE: Delay in seeking medical care is one criterion used to
      identify victims of abuse. However, typical symptoms of accidental fractures in
      young children and the time between injury and the seeking of medical care have
      not been reported. We describe patient and injury characteristics that influence
      the time from injury to medical care. METHODS: Parental interviews were conducted
      for children <6 years old with accidental extremity fractures. Demographic
      characteristics, signs and symptoms of the injury, and fracture location and
      severity were described and examined for their association with a delay (>8
      hours) in seeking medical care. RESULTS: Among 206 children, 69% had upper
      extremity fractures. The median time to the first medical evaluation was 1 hour,
      but 21% were seen at >8 hours after injury. Although 91% of children cried after
      the injury, only 83% were irritable for >30 minutes. Parents observed no external
      sign of injury in 15% of children, and 12% used the injured extremity normally.
      However, all parents noted at least 1 sign or symptom. Minority children (odds
      ratio [OR]: 2.54 [95% confidence interval [CI]: 1.18-5.47), those with lower
      extremity injuries (OR: 2.23 [95% CI: 1.01-4.90]), those without external signs
      of injury (OR: 3.40 [95% CI: 1.36-8.51]), and those with continued extremity use
      (OR: 3.26 [95% CI: 1.22-8.76]) were more likely to delay seeking medical care.
      CONCLUSIONS: Although some children did not manifest all expected responses, no
      child with an accidental fracture was asymptomatic. Delay in seeking medical care
      was associated with more subtle signs of injury; however, delays identified in
      minority patients are unexplained.

PMID- 22144697
TI  - Trends in preventive asthma medication use among children and adolescents, 1988
      2008.
AB  - OBJECTIVE: To examine trends in preventive asthma medication (PAM) use among
      children with current asthma in the United States from 1988 to 2008. METHODS: We
      performed a cross-sectional analysis of PAM use among 2499 children aged 1 to 19
      years with current asthma using nationally representative data from the National
      Health and Nutrition Examination Survey (NHANES) during 3 time periods: 1988
      1994, 1999-2002, and 2005-2008. PAMs included inhaled corticosteroids,
      leukotriene receptor antagonists, long-acting beta-agonists, mast-cell
      stabilizers, and methylxanthines. RESULTS: Among children with current asthma,
      there was an increase in the use of PAMs from 17.8% (SE: 3.3) in 1988-1994 to
      34.9% (SE: 3.3) in 2005-2008 (P < .001 for trend). Adjusting for age, gender,
      race/ethnicity, and health insurance status, the odds of PAM use were higher in
      2005-2008 compared with 1988-1994 (adjusted odds ratio [aOR] = 2.6; 95%
      confidence interval [CI]: 1.5-4.5). A multivariate analysis, combining all 3 time
      periods, showed lower use of PAMs among non-Hispanic black (aOR = 0.5 [95% CI:
      0.4-0.7]) and Mexican American (aOR = 0.6 [95% CI: 0.4-0.9]) children compared to
      non-Hispanic white children. PAM use was also lower in 12 to 19 year olds
      compared with 1 to 5 year olds and also in children who did not have health
      insurance compared with those who did. CONCLUSIONS: Between 1988 and 2008, the
      use of PAM increased among children with current asthma. Non-Hispanic black and
      Mexican American children, adolescents aged 12 to 19 years, and uninsured
      children with current asthma had lower use of PAM.

PMID- 22144698
TI  - Antihypertensive prescribing patterns for adolescents with primary hypertension.
AB  - BACKGROUND: Hypertension is an increasingly common problem in adolescents yet
      current medical management of primary hypertension in adolescents has not been
      well-described. METHODS: We identified adolescents with primary hypertension by
      International Classification of Diseases, Ninth Revision codes and looked at
      prescription patterns chronologically for antihypertensive drug class prescribed
      and the specialty of prescribing physician. We also examined patient demographics
      and presence of obesity-related comorbidities. RESULTS: During 2003-2008, there
      were 4296 adolescents with primary hypertension (HTN); 66% were boys; 73% were
      aged 11 to 14 years; 53% were black, 41% white, and 4% Hispanic; and 48% had
      obesity-related comorbidity. Twenty-three percent (977) received antihypertensive
      prescription. White subjects (odds ratio [OR]: 1.61; confidence interval [CI]:
      1.39-1.88), older adolescents (>=15 years, OR: 2.11; CI: 1.79-2.48), and those
      with comorbidity (OR: 1.57; CI: 1.36-1.82) were more likely to receive
      antihypertensive prescriptions controlling for gender and years of Medicaid
      eligibility in logistic regression. Angiotensin converting enzyme inhibitors were
      the most frequently prescribed monotherapy. Nearly two-thirds of adolescents
      received prescriptions from adult primary care physicians (PCPs) only. More than
      one-quarter of adolescents who received a prescription received combination
      therapy, which was most often prescribed by adult PCPs. CONCLUSIONS: Adult PCPs
      were the leading prescribers of antihypertensives for adolescents with primary
      HTN. Race differences exist in physicians' prescribing of antihypertensives to
      adolescents with primary HTN. The choice of antihypertensives by physicians of
      different specialties warrants additional study to understand the underlying
      rationale for treatment decisions and to determine treatment effectiveness.

PMID- 22144699
TI  - Corticosteroid pulse combination therapy for refractory Kawasaki disease: a
      randomized trial.
AB  - OBJECTIVE: This study examined the clinical efficacy and safety of intravenous
      methylprednisolone-pulse plus intravenous immunoglobulin (IVIG) combination
      therapy (IVMP+IVIG) for the initial treatment of patients predicted to have
      refractory Kawasaki disease (KD). METHODS: One hundred twenty-two patients with
      KD were studied at Kitasato University. Refractory KD was predicted at diagnosis
      using the Egami score, and the patients were randomly divided to receive either
      IVMP+IVIG or IVIG alone. The Egami score is used to predict refractory KD
      patients before treatment using the patient's age, days of illness, platelet
      count, C-reactive protein, and alanine aminotransferase level (cutoff: >=3
      points; 78% sensitivity and 76% specificity). RESULTS: Forty-eight patients
      (39.3%) were predicted to have refractory KD on the basis of the Egami score. The
      predicted IVIG responders (n = 74) received the standard therapy. The 48
      predicted refractory KD patients were randomly assigned to a single-IVIG group (n
      = 26) or an IVMP+IVIG group (n = 22). Nineteen of the 22 patients (86.4%) in the
      IVMP+IVIG group had a prompt defervescence compared with 6 of the 26 patients
      (23.1%) in the single-IVIG group. The number of patients who had a z score >=2.5
      at 1 month was significantly higher in the single-IVIG group than in the
      IVMP+IVIG group. No serious adverse events were observed in either treatment
      group. CONCLUSION: This study demonstrated that IVMP+IVIG therapy is safe and
      effective for KD patients predicted as refractory.

PMID- 22144700
TI  - Wide variation in reference values for aluminum levels in children.
AB  - BACKGROUND: Some parents are requesting aluminum testing in their children with
      developmental issues. Although aluminum can be measured in plasma, serum, or
      urine, there is scant scientific information about normal ranges. We sought to
      determine the basis for laboratory reference ranges and whether these ranges are
      applicable to children. METHODS: From texts, published lists, and Internet
      sources, we obtained the names of 10 clinical laboratories that perform aluminum
      testing. Contact was made by telephone or e-mail, or Internet sites were viewed
      to obtain information regarding the establishment of aluminum reference ranges
      and testing methods in biological samples. Seven laboratories provided supporting
      literature that was reviewed regarding details of the study populations. RESULTS:
      For laboratories using the atomic absorption spectrometry method, aluminum
      reference ranges varied from <5.41 MUg/L to <20 MUg/L (serum), <7.00 MUg/L to 0
      to 10 MUg/L (plasma) and 5 to 30 MUg/L (urine). For those using the inductively
      coupled plasma mass spectroscopy methodology, ranges varied from 0 to 6 MUg/L to
      <42 MUg/L (serum), 0 to 10 MUg/L to 0 to 15 MUg/L (plasma), and 0 to 7 MUg/L to 5
      to 30 MUg/L (urine). None of the reference ranges are known to be derived from
      studies of healthy children, but relied instead on small studies of adult
      populations, adult dialysis patients, workers, or sick children on aluminum
      containing parenteral therapy. CONCLUSIONS: Aluminum reference ranges provided by
      laboratories are widely divergent, may not represent "normal" ranges of a healthy
      population, especially children, and thus it is difficult to interpret serum or
      urine aluminum ranges clinically. Further studies of aluminum in children are
      warranted and should be considered as part of the Centers for Disease Control and
      Prevention Biomonitoring Project.

PMID- 22144701
TI  - Unmanipulated donor lymphocytes for EBV-related PTLD after T-cell depleted HLA
      haploidentical transplantation.
AB  - Epstein-Barr virus (EBV)-related post-transplantation lymphoproliferative
      disorder (PTLD) is a life-threatening complication in patients given T-cell
      depleted hematopoietic stem cell transplantation from an HLA-haploidentical
      relative (haplo-HSCT). We report the case of a child who developed severe EBV
      related PTLD after haplo-HSCT from his mother. Despite receiving the anti-CD20
      monoclonal antibody, the patient presented with intestinal obstruction due to
      huge abdominal lymphadenopathy, hematemesis, and nodulary pulmonary lesions.
      Histology showed that the lesions were due to CD20-/CD19+ large neoplastic B
      cells. The patient underwent double intestinal resection with partial abdominal
      lymphadenectomy and then received 3 monthly doses of donor-derived unmanipulated
      mononuclear cells. The initial dose of CD3+ cells was 3 10(5)/kg recipient body
      weight. The 2 additional doses consisted of 5 10(5) CD3+ cells/kg. No sign or
      symptom attributable to graft-versus-host disease was observed, and the patient
      completely cleared EBV-related lesions. The child was disease-free for 13 months
      after the first lymphocyte infusion. This case demonstrates that repeated
      infusions of controlled numbers of donor CD3+ cells cure EBV-related PTLD in
      haplo-HSCT without inducing graft-versus-host disease.

PMID- 22144702
TI  - Sustained reduction in neonatal nosocomial infections through quality improvement
      efforts.
AB  - BACKGROUND: Although reports of reduced nosocomial infections (NI) in very low
      birth weight infants have been published, the durability of these gains and
      changes in secondary outcomes, and clinical practices have less often been
      published. METHODS: This was a retrospective, observational study of NI reduction
      in very low birth weight infants at two hospital campuses. The intervention began
      in 2005 with our renewed quality improvement efforts to reduce NI. We compared
      outcomes before (2000-2005) and after (2006-2009) the intervention by using
      univariate and multiple regression analyses. RESULTS: We reduced NI by 50%
      comparing 2000-2005 to 2006-2009 (23.6% vs 11.6%, P < .001). Adjusting for
      covariates, the odds ratio for NI was 0.33 (confidence interval, 0.26 - 0.42, P <
      .001) in the more recent era. NI were lower even in infants with birth weight 501
      1000 grams (odds ratio = 0.38, confidence interval, 0.29 - 0.51, P < .001). We
      also reduced bronchopulmonary dysplasia (30.2% vs 25.5%, P = .001), median days
      to regain birth weight (9 vs 8, P = .04), percutaneously placed central venous
      catheter use (54.8% vs 43.9%, P = .002), median antibiotic days (8 vs 6, P =
      .003), median total central line days (16 vs 15, P = .01), and median ventilator
      days (7 vs 5, P = .01). We sustained improvements for three years. CONCLUSIONS:
      Quality improvement efforts were associated with sustained reductions in NI,
      bronchopulmonary dysplasia, antibiotic use, central line use, and ventilator
      days.

PMID- 22144703
TI  - Testing children for adult-onset genetic diseases.

PMID- 22144704
TI  - Mosaic 7q31 deletion involving FOXP2 gene associated with language impairment.
AB  - We report on a 10-year-old patient with childhood apraxia of speech (CAS) and
      mild dysmorphic features. Although multiple karyotypes were reported as normal, a
      bacterial artificial chromosome array comparative genomic hybridization revealed
      the presence of a de novo 14.8-Mb mosaic deletion of chromosome 7q31. The deleted
      region involved several genes, including FOXP2, which has been associated with
      CAS. Interestingly, the deletion reported here was observed in about 50% of
      cells, which is the first case of mosaicism in a 7q31 deletion. Despite the
      presence of the deletion in only 50% of cells, the phenotype of the patient was
      not milder than other published cases. To date, 6 cases with a deletion of 9.1-20
      Mb involving the FOXP2 gene have been reported, suggesting a new contiguous gene
      deletion syndrome characterized mainly by CAS caused by haploinsufficiency of the
      genes encompassed in the 7q critical region. This report suggests that children
      found with a deletion involving the FOXP2 region should be evaluated for CAS and
      that analysis of the FOXP2 gene including array comparative genomic hybridization
      should be considered in selected patients with CAS. Mosaic deletions in this area
      may also be considered as causative of CAS.

PMID- 22144705
TI  - Translational research in pediatrics: tissue sampling and biobanking.
AB  - Translational research is expanding and has become a focus of National Research
      funding agencies, touted as the primary avenue to improve health care practice.
      The use of human tissues for research on disease etiology is a pillar of
      translational research, particularly with innovations in research technologies to
      investigate the building blocks of disease. In pediatrics, translational research
      using human tissues has been hindered by the many practical and ethical
      considerations associated with tissue procurement from children and also by a
      limited population base for study, by the increasing complexities in conducting
      clinical research, and by a lack of dedicated child-health research funding.
      Given these obstacles, pediatric translational research can be enhanced by
      developing strategic and efficient biobanks that will provide scientists with
      quality tissue specimens to render accurate and reproducible research results.
      Indeed, tissue sampling and biobanking within pediatric academic settings has
      potential to impact child health by promoting bidirectional interaction between
      clinicians and scientists, helping to maximize research productivity, and
      providing a competitive edge for attracting and maintaining high-quality
      personnel. The authors of this review outline key issues and practical solutions
      to optimize pediatric tissue sampling and biobanking for translational research,
      activities that will ultimately reduce the burden of childhood disease.

PMID- 22144706
TI  - Prevalence and characteristics of youth sexting: a national study.
AB  - OBJECTIVES: To obtain national estimates of youth involved in sexting in the past
      year (the transmission via cell phone, the Internet, and other electronic media
      of sexual images), as well as provide details of the youth involved and the
      nature of the sexual images. METHODS: The study was based on a cross-sectional
      national telephone survey of 1560 youth Internet users, ages 10 through 17.
      RESULTS: Estimates varied considerably depending on the nature of the images or
      videos and the role of the youth involved. Two and one-half percent of youth had
      appeared in or created nude or nearly nude pictures or videos. However, this
      percentage is reduced to 1.0% when the definition is restricted to only include
      images that were sexually explicit (ie, showed naked breasts, genitals, or
      bottoms). Of the youth who participated in the survey, 7.1% said they had
      received nude or nearly nude images of others; 5.9% of youth reported receiving
      sexually explicit images. Few youth distributed these images. CONCLUSIONS:
      Because policy debates on youth sexting behavior focus on concerns about the
      production and possession of illegal child pornography, it is important to have
      research that collects details about the nature of the sexual images rather than
      using ambiguous screening questions without follow-ups. The rate of youth
      exposure to sexting highlights a need to provide them with information about
      legal consequences of sexting and advice about what to do if they receive a
      sexting image. However, the data suggest that appearing in, creating, or
      receiving sexual images is far from being a normative behavior for youth.

PMID- 22144707
TI  - How often are teens arrested for sexting? Data from a national sample of police
      cases.
AB  - OBJECTIVE: To examine characteristics of youth sexting cases handled by police
      and their outcomes in response to clinical and other concerns about the risks of
      sexting behavior. METHODS: Mail surveys were sent to a stratified national sample
      of 2712 law enforcement agencies followed by detailed telephone interviews with
      investigators about a nationally representative sample of sexting cases handled
      by police during 2008 and 2009 (n = 675). The cases involved "youth-produced
      sexual images" that constituted child pornography under relevant statutes
      according to respondents. RESULTS: US law enforcement agencies handled an
      estimated 3477 cases of youth-produced sexual images during 2008 and 2009 (95%
      confidence interval: 3282-3672). Two-thirds of the cases involved an
      "aggravating" circumstance beyond the creation and/or dissemination of a sexual
      image. In these aggravated cases, either an adult was involved (36% of cases) or
      a minor engaged in malicious, non-consensual, or abusive behavior (31% of cases).
      An arrest occurred in 62% of cases with an adult involved, in 36% of the
      aggravated youth-only cases, and in 18% of the "experimental" cases (youth-only
      and no aggravating elements). Most of the images (63%) were distributed by cell
      phone only and did not reach the Internet. Sex offender registration applied in
      only a few unusual cases. CONCLUSIONS: Many of the youth sexting cases that come
      to the attention of police include aggravating circumstances that raise concerns
      about health and risky sexual behavior, although some cases were relatively
      benign. Overall, arrest is not typical in cases with no adults involved.

PMID- 22144708
TI  - Headache after pediatric traumatic brain injury: a cohort study.
AB  - OBJECTIVE: To determine the prevalence of headache 3 and 12 months after
      pediatric traumatic brain injury (TBI). METHODS: This is a prospective cohort
      study of children ages 5 to 17 years in which we analyzed the prevalence of
      headache 3 and 12 months after mild TBI (mTBI; n = 402) and moderate/severe TBI
      (n = 60) compared with controls with arm injury (AI; n = 122). RESULTS: The
      prevalence of headache 3 months after injury was significantly higher after mTBI
      than after AI overall (43% vs 26%, relative risk [RR]: 1.7 [95% confidence
      interval (CI): 1.2-2.3]), in adolescents (13-17 years; 46% vs 25%, RR: 1.8 [95%
      CI: 1.1-3.1]), and in girls (59% vs 24%, RR: 2.4 [95% CI: 1.4-4.2]). The
      prevalence of headache at 3 months was also higher after moderate/severe TBI than
      AI in younger children (5-12 years; 60% vs 27%; RR: 2.0 [95% CI: 1.2-3.4]).
      Twelve months after injury, TBI was not associated with a significantly increased
      frequency of headache. However, girls with mTBI reported serious headache (>= 5
      of 10 pain scale rating) more often than controls (27% vs 10%, RR: 2.2 [95% CI:
      0.9-5.6]). CONCLUSIONS: Pediatric TBI is associated with headache. A substantial
      number of children suffer from headaches months after their head injury. The
      prevalence of headache during the year after injury is related to injury
      severity, time after injury, age, and gender. Girls and adolescents appear to be
      at highest risk of headache in the months after TBI.

PMID- 22144710
TI  - Dengue vector surveillance programs: a review of methodological diversity in some
      endemic and epidemic countries.
AB  - Vector surveillance is a cornerstone of dengue management yet there is a
      diversity of surveillance programs evident internationally. Such diversity is
      described in this review to enable a broader assessment of dengue vector
      surveillance methods. This review describes the diversity of surveillance
      programs for dengue vectors in several endemic and epidemic countries.
      Furthermore, strengths and weaknesses of vector surveillance methods, including
      larval surveys, BG-Sentinel trap, and autocidal and sticky ovitraps, are also
      discussed. The ability to compare and contrast these programs could contribute to
      the finding of better methods both locally and nationally and facilitate
      interregional technology transfer. Health authorities in both endemic and
      epidemic countries alike could benefit from adopting technologies and practices
      from other regions.

PMID- 22144711
TI  - Differences between the factors affecting high-risk drinking and those affecting
      smoking in Korea.
AB  - This study examines the factors influencing high-risk drinking and cigarette
      smoking and assesses the differences in those factors between 2 risky behaviors
      in Korea. A national, cross-sectional health behavior survey was performed on
      12,303 households in 2006 and a data set of 2925 adult males was analyzed using
      bivariate probit estimation model. The likelihood of high-risk drinking rose with
      an increase in the level of income, whereas that of smoking was lowest in a
      medium income. White-collar workers were more at risk of high-risk drinking than
      blue-collar workers. Conversely, blue-collar workers tended to smoke more
      frequently than white-collar workers. Body mass index showed a positive
      association with high-risk drinking, but it had no significant relationship with
      smoking. Significant differences may exist in associations between factors
      influencing high-risk drinking and those influencing smoking. The comprehensive
      understanding of these differences would allow for the development of appropriate
      public health programs.

PMID- 22144712
TI  - Rural-urban comparison in prevalence of overweight and obesity among children and
      adolescents of Asian Indian origin.
AB  - OBJECTIVES: To study whether the prevalence of overweight and obesity in children
      and adolescents is restricted by habitat (urban vs rural). METHODS: A total of
      753 healthy children and adolescents, out of which 293 (159 boys and 134 girls)
      were collected Santiniketan (rural area) and 460 (241 boys and 219 girls) were
      from Calcutta and the suburbs (urban area), aged 8 to 18 years took part in the
      study. Participants were subsequently divided into 3 age groups: group I, 8 to 12
      years; group II, 13 to 15 years, and group III, 16 to 18 years. RESULTS: It was
      observed that the overall prevalence of overweight and obesity in the study was
      9.6% and 5.7%, respectively. Urban residence and high level of parental education
      are associated with overweight and obesity in children and adolescents (R(2) =
      40.3%). CONCLUSION: Prevalence of overweight and obesity among children and
      adolescents is not restricted to any particular habitat and warrants early
      intervention if this global epidemic is to be checked.

PMID- 22144713
TI  - Knowledge of danger signs for major obstetric complications among pregnant
      KwaZulu-Natal women: implications for health education.
AB  - OBJECTIVES: The explicit objectives of the present study were to assess the level
      of knowledge on pregnancy "danger signs" and HIV status, estimate the proportion
      of pregnant women uses health care facilities, and identify sociodemographic
      predictors. METHODS: A cross-sectional community-based study was conducted by
      means of a questionnaire survey among 340 black pregnant women from the province
      of KwaZulu-Natal. RESULTS: The mean age of the pregnant women was 26 years where
      teenage pregnancy rate was 13%. Most of the pregnant women were single (78%),
      less educated (60%), and unemployed (92%). Though most of the study population
      (92%) attended health care facilities, only half (52%) of them knew about some of
      the "danger signs" of pregnancy, and 39% of them knew about their HIV status.
      Known HIV status was related to the knowledge of pregnancy complication (P =
      .018). Knowledge of "danger signs" of pregnancy was significantly (P = .012)
      associated with the age of the expectant mother. CONCLUSION: Low level of
      knowledge on "danger signs" of pregnancy and their HIV status are observed among
      pregnant women. This warrants an urgent attempt to introduce health education
      strategies to rural population of South Africa.

PMID- 22144714
TI  - Concentrations and size distribution of inhalable and respirable dust among sugar
      industry workers: a pilot study in Khon Kaen, Thailand.
AB  - There has been very limited information regarding bagasse exposure among workers
      in sugar industries as well as on health outcomes. The authors determined the
      occupational exposure of sugar industry workers in Khon Kaen to airborne bagasse
      dust. The size of the bagasse dust ranged from 0.08 to 9 um with the highest size
      concentration of 2.1 to 4.7 um. The most common size had a geometric mean
      diameter of 5.2 um, with a mass concentration of 6.89 mg/m(3)/log um. The highest
      mean values of inhalable and respirable dust were found to be 9.29 mg/m(3) from
      February to April in bagasse storage, 5.12 mg/m(3) from May to September, and
      4.12 mg/m(3) from October to January. Inhalable dust concentrations were 0.33,
      0.47, and 0.41 mg/m(3), respectively. Workers are likely to be exposed to high
      concentrations of bagasse dust and are at risk of respiratory diseases.
      Preventive measures, both in the form of engineering designs and personal
      protective devices, should be implemented.

PMID- 22144715
TI  - Betel chewing and public health.

PMID- 22144716
TI  - Cellular network based drug monitoring.
AB  - Pharmacovigilance is a resourceful process for monitoring adverse drug reactions.
      The lack of resources in developing countries makes it difficult to execute
      pharamcovigilance programs on a large scale. Therefore, the cellular technology
      based network, which has widespread access in the developing world, may be used
      as an inexpensive means of monitoring.

PMID- 22144717
TI  - K(ATP) channel openers in the trigeminovascular system.
AB  - BACKGROUND: The ATP-sensitive K(+) (K(ATP)) channel openers levcromakalim and
      pinacidil are vasodilators that induce headache in healthy people. The
      neuropeptide calcitonin gene-related peptide (CGRP) induces headache in healthy
      people and migraine in migraineurs, potentially through a mechanism that involves
      opening of vascular or neuronal K(ATP) channels and mast cell degranulation.
      Using rat as a model, we studied the molecular presence of K(ATP) channels in the
      trigeminovascular system. Furthermore, we examined whether K(ATP) channel openers
      stimulate the in vitro release of CGRP and whether they degranulate dural mast
      cells. METHODS: mRNA and protein expression of K(ATP) channel subunits were
      studied in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) by
      qPCR and western blotting. In vitro CGRP release was studied after application of
      levcromakalim (1 uM) and diazoxide (10 uM) to freshly isolated rat dura mater, TG
      and TNC. Rat dural mast cells were challenged in situ with levcromakalim (10(-5)
      M) to study its potential degranulation effect. RESULTS: mRNA and protein of
      K(ATP) channel subunits Kir6.1, Kir6.2, SUR1 and SUR2B were identified in the TG
      and TNC. K(ATP) channel openers did not release or inhibit capsaicin-induced CGRP
      release from dura mater, TG or TNC. They did also not induce dural mast cell
      degranulation. CONCLUSIONS: K(ATP) channel openers do not interact with CGRP
      release or mast cell degranulation. Activation of these channels in the CNS is
      antinociceptive and therefore cannot explain the headache induced by K(ATP)
      channel openers. Thus, they are likely to induce headache by interaction with
      extracerebral K(ATP) channels, probably the SUR2B isoforms.

PMID- 22144719
TI  - Neonatal diabetes mellitus in China: a case report and review of the Chinese
      literature.
AB  - To recognize the clinical characteristics and outcomes of neonatal diabetes
      mellitus (NDM), the authors retrospectively reviewed 1 NDM baby in their
      department and compared their data with 39 NDM cases reported in the available
      Chinese literature between January 1986 and December 2010. Most of the cases were
      located near the eastern and southern coasts of China, and clinical manifestation
      of 72.5% of the cases occurred in 4-week-old infants. Hyperglycemia and
      glycosuria findings were seen in all the patients and in 47.5% with intrauterine
      growth retardation. Moreover, 30.0% of the cases had polyuria, 52.5% had
      dehydration, and 47.5% had ketoacidosis. Cases with hyperglycemia, dehydration,
      and ketoacidosis recovered mostly. Ten NDM cases had persisted after 1 to 11
      years of follow-up, 3 cases maintained normal blood sugar, and 7 cases had poor
      sugar control. NDM is a rare condition and early management includes fluid and
      insulin and later management depends on the transient or permanent nature of the
      condition.

PMID- 22144720
TI  - The perinatal infection of cytomegalovirus is an important etiology for biliary
      atresia in China.
AB  - AIMS: The aims of this study were to detect the infection rates of DNA viruses in
      liver tissue of biliary atresia and to investigate the effect of perinatal
      infection of cytomegalovirus in biliary atresia. METHODS: A total of 85 liver
      biopsies (taken during Kasai portoenterostomy) were tested by fluorescence
      quantitative polymerase chain reaction for DNA viruses (herpes simplex virus
      [HSV], Epstein-Barr virus [EBV], varicella zoster virus [VZV], cytomegalovirus
      [HCMV], and adenovirus). Immunocytochemical detection of CMV-pp65 antigenemia
      assay was used to detect the presence of viral protein in liver samples. Human
      intrahepatic biliary epithelial cells was infected by the laboratory strain AD169
      of HCMV in vitro. RESULTS: Virus DNA was found in the biopsies (51/85 HCMV, 5/85
      ADV, 3/85 EBV). The biopsies of 2 patients were tested positive for 2 viruses
      simultaneously. They include one case of HCMV in combination with ADV and one
      case of ASV in combination with EBV. CMV-pp65 antigenemia were distributed in
      hepatocyte, vascular endothelial cell, and biliary duct endothelial cell. The
      cytopathic effect and apoptosis were observed after HCMVAD169 infected human
      intrahepatic biliary epithelial cells at 6 days. CONCLUSION: Human intrahepatic
      biliary epithelial cell is the target cell of HCMV. The etiology of biliary
      atresia is probably multifactorial. The perinatal infection of HCMV is one of the
      important etiologies for biliary atresia in China.

PMID- 22144718
TI  - Local action of the proinflammatory cytokines IL-1beta and IL-6 on intracranial
      meningeal nociceptors.
AB  - BACKGROUND: Peripheral nociceptive action of the proinflammatory cytokines IL
      1beta and IL-6 has been implicated in the pathogenesis of numerous pain
      syndromes. An increase in the level of these cytokines in jugular venous blood
      has been reported during migraine attacks, suggesting their potential involvement
      in mediating the intracranial headache of migraine. METHODS: In this work we
      examined, using in vivo single-unit recording of meningeal nociceptors in the
      trigeminal ganglion of anesthetized rats, whether the peripheral actions of IL
      1beta and IL-6 can promote the activation and sensitization of nociceptors that
      innervate the intracranial meninges, two neural processes that are believed to
      play a key role in promoting the intracranial throbbing pain of migraine.
      RESULTS: We found that meningeal application of IL-1beta leads to the activation
      and mechanical sensitization of about 70% and 45% of the nociceptors
      respectively. In contrast, IL-6 was a very poor modulator of meningeal
      nociceptors' response properties affecting overall only about 20% of the
      nociceptors. CONCLUSIONS: Our study provides for the first time in vivo
      electrophysiological evidence that meningeal action of IL-1beta can promote the
      activation and increased mechanosensitivity of intracranial meningeal nociceptors
      and that IL-6 generally lacks these properties. Future studies are required to
      examine the mechanism that plays a role in mediating the nociceptive effects of
      IL-1beta on meningeal nociceptors, which may serve as a target for migraine
      therapy.

PMID- 22144721
TI  - Randomized controlled study of the efficacy of the injection of botulinum toxin
      type A versus corticosteroids in chronic plantar fasciitis: results at one and
      six months.
AB  - OBJECTIVE: To determine the efficacy of botulinum toxin type A in chronic plantar
      fasciitis compared to the local injection of a corticosteroid plus local
      anaesthetic. METHODS: Patients with a clinical diagnosis of plantar fasciitis
      made at least six months earlier were selected to enter a randomized, single
      blind study of treatment with injections of botulinum toxin type A or
      corticosteroid. There were 28 patients in each treatment group. Patients were
      evaluated at one month using the Foot Health Square Questionnaire and those with
      no clinical response subsequently received a second injection with the drug of
      the other arm of the study, creating two new treatment groups. Re-evaluation was
      performed at six months. RESULTS: One month after injection there was a clear
      clinical improvement in both treatment groups but it was greater in the botulinum
      toxin group, with a significant difference for the pain item (P = 0.069), though
      not in other items. At six months, patients treated with botulinum toxin type A
      had continued to improve in all items, whereas the corticosteroid group lost part
      of the improvement achieved at one month (improvement with botulinum toxin vs.
      corticosteroid: pain 19.10/-6.84 (P = 0.001), function 16.00/-8.80 (P < 0.001),
      footwear 13.48/-7.95 (P = 0.004), self-perceived foot health 25.44/-5.41 (P <
      0.001). CONCLUSION: Botulinum toxin type A should be considered for the treatment
      of chronic plantar fasciitis in view of the improvement found at one month, and
      particularly at six months, when this treatment clearly has better results than
      corticosteroid injections. Further studies with larger samples are necessary to
      confirm these results.

PMID- 22144722
TI  - Evaluation of the effect of balneotherapy in patients with osteoarthritis of the
      hands: a randomized controlled single-blind follow-up study.
AB  - OBJECTIVE: To evaluate the effectiveness of thermal mineral water compared with
      magnetotherapy without balneotherapy as control, in the treatment of hand
      osteoarthritis. DESIGN: Randomized controlled single-blind follow-up study.
      SETTING: Rheumatology specialist clinic of Gunaras Health Spa. SUBJECTS: Patients
      between 50 and 70 years of age with hand osteoarthritis, randomly assigned into
      three groups. INTERVENTIONS: The subjects in the first two groups bathed in
      thermal mineral water of two different temperatures (36 degrees C and 38 degrees
      C) for three weeks five times a week for 20 minutes a day and received
      magnetotherapy to their hands three times weekly. The third group received only
      magnetotherapy. OUTCOME MEASURES: Visual analogue scale scores, handgrip
      strength, pinchgrip strength, the number of swollen and tender joints of the
      hand, the duration of morning joint stiffness, Health Assessment Questionnaire,
      and Short Form-36 questionnaire. The study parameters were administered at
      baseline, immediately after treatment and after 13 weeks. RESULTS: The study
      included 63 patients. Statistically significant improvement was observed in
      several studied parameters after the treatment and during the follow-up study in
      the thermal water groups versus the control group. The 38 degrees C thermal water
      treatment significantly improved the pinch strength of the right hand (0.6 (95%
      confidence interval (CI) 0.2 to 1.1) vs. 0.03 (95% CI -0.3 to 0.4), P < 0.05) and
      the Health Assessment Questionnaire parameters (-0.4 (95% CI -0.6 to -0.2) vs. 
      0.1 (95% CI -0.2 to 0.1), P < 0.01) even in the long term. CONCLUSIONS:
      Balneotherapy combined with magnetotherapy improved the pain and function as well
      as the quality of life in patients with hand osteoarthritis.

PMID- 22144723
TI  - Disease-specific training in Parkinson's disease for care assistants: a
      comparison of interactive and self-study methods.
AB  - OBJECTIVE: To compare two approaches to providing training to care assistants in
      Parkinson's disease. DESIGN: Pragmatic parallel arm controlled trial. SETTING:
      Training either by an interactive training day at a local medical education
      establishment or self study. SUBJECTS: Care assistants recruited from local
      health and social care providers. INTERVENTIONS: The content of both
      interventions was similar, covering causes, symptoms, diagnosis of Parkinson's
      disease, multidisciplinary management, mobility, communication, swallowing, and
      involving 5 hours of study time. MAIN MEASURES: Knowledge about Parkinson's
      (assessed by true/false quizzes and identifying 'four facts' about Parkinson's)
      immediately post training and six weeks later; views on training methods of care
      assistants and employers/managers. RESULTS: Thirty-seven employers nominated 100
      care staff who were allocated to interactive training (49) and self study (51).
      Training completion rates (retained to six-week follow-up) were lower for self
      study (42.1% vs. 83.7% training day). There were no significant differences
      between groups on quiz or 'four facts' scores at baseline or six-week follow-up.
      Immediately post training, the self-study group (with access to written
      materials) had significantly higher quiz scores than the training day group (no
      access to materials at test). Within-group comparisons showed improvements post
      training. Although interactive training may be preferred, obtaining release from
      duties can be problematic. CONCLUSIONS: Both approaches have similar effects on
      knowledge of care assistants without prior specific training. Providing a variety
      of approaches will cater for all preferences. The findings may be generalizable
      to training the care workforce for other specific roles.

PMID- 22144724
TI  - Effect of a multidisciplinary rehabilitation programme on perceived health among
      employees at increased risk of incapacity for work: a controlled study.
AB  - OBJECTIVE: To evaluate the effect of a four-week primary prevention programme on
      change in perceived health among employees at increased risk of incapacity for
      work. DESIGN: A follow-up controlled study. SETTINGS: The data were collected
      from survey responses and registered data on demographic, work and health
      characteristics, and health-related behaviours. SUBJECTS: Eight hundred and
      seventy-two participants and their 2440 propensity score-matched controls.
      INTERVENTION: Multidisciplinary preventive programme of physical training and
      psychological education to adopt a healthier lifestyle, and to achieve greater
      aerobic capacity, muscle strength and endurance, as well as better self
      management of stress. MAIN MEASURES: Psychological distress, anxiety and
      suboptimal self-rated health. RESULTS: The prevalence of suboptimal self-rated
      health, psychological distress and anxiety did not differ between the
      participants and controls before the intervention (22.6% vs. 22.8%, 26.6% vs.
      29.0%, and 33.0% vs. 33.8%, respectively). Similarly, after the intervention,
      there were no group differences in the prevalence of self-rated health problems
      at the time of the short-term (mean 1.7 years, up to 4.6 years) or long-term
      (mean 5.8 years, up to 9.2 years) follow-up. Figures for prevalence of suboptimal
      self-rated health, psychological distress and anxiety in participants and
      controls at the time of the long-term follow-up were 33.8% vs. 28.9%, 25.1% vs.
      24.9%, and 34.7% vs. 33.2%, respectively. CONCLUSIONS: No beneficial effects on
      perceived health were observed for a four-week primary prevention programme
      widely used in Finland to reduce early retirement on health grounds.

PMID- 22144725
TI  - Early mobilization out of bed after ischaemic stroke reduces severe complications
      but not cerebral blood flow: a randomized controlled pilot trial.
AB  - OBJECTIVE: To evaluate whether early mobilization after acute ischaemic stroke is
      better than delayed mobilization with regard to medical complications and if it
      is safe in relation to neurological function and cerebral blood flow. DESIGN:
      Randomized controlled pilot trial of early versus delayed mobilization out of bed
      with incidence of severe complications as the primary outcome. SETTING: Acute
      stroke unit in the neurology department of a University Hospital. PARTICIPANTS:
      Fifty patients after ischaemic stroke with a National Institutes of Health Stroke
      Scale (NIHSS) score >6 were recruited. INTERVENTION: All patients were treated
      with physiotherapy immediately after their admission. In the early protocol
      patients were mobilized out of bed after 52 hours, in the delayed protocol after
      seven days. RESULTS: Eight out of 50 randomized patients were excluded from the
      per-protocol analysis because of early transfer to other hospitals. There were 2
      (8%) severe complications in the 25 early mobilization patients and 8 (47%) in
      the 17 delayed mobilization patients (P < 0.006). There were no differences in
      the total number of complications or in clinical outcome. In the 26 patients
      (62%) who underwent serial transcranial Doppler ultrasonography, no blood flow
      differences were found. CONCLUSION: We found an apparent reduction in severe
      complications and no increase in total complications with an early mobilization
      protocol after acute ischaemic stroke. No influence on neurological three-month
      outcomes or on cerebral blood flow was seen. These results justify larger trials
      comparing mobilization protocols with possibly even faster mobilization out of
      bed than explored here.

PMID- 22144726
TI  - Evaluation of wound-healing formulation against sulphur mustard-induced skin
      injury in mice.
AB  - Sulphur mustard (SM) is a bifunctional alkylating agent that causes cutaneous
      blisters in human and animals. Remedies to SM-induced dermatotoxicity are still
      in experimental stage. Due to inevitable requirement of a wound-healing
      formulation against SM-induced skin lesions, efficacy of formulations including
      povidone iodine, Aloe vera gel, betaine or framycetin sulphate was evaluated in
      present study. SM was applied percutaneously (5 mg/kg) once on back region of
      Swiss albino mice; and after 24 hours, DRDE/WH-02 (Defence Research and
      Development Establishment/ Wound Healant- 02, containing polyvinylpyrrolidone
      [PVP], A. vera gel and betaine), Ovadine, Soframycin or A. vera gel were applied
      topically, daily for 3 or 7 days in different groups. Skin sections were
      subjected to histopathology, histomorphologic grading, tissue leukocytosis,
      terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and
      immunohistochemistry of inflammatory-reparative biomarkers. DRDE/WH-02 treated
      mice received highest score on the basis of histomorphologic scale and lowest
      number of TUNEL-positive cells compared to other groups. DRDE/WH-02 showed better
      wound healing as evidenced by widespread re-epithelialization, homogenous
      fibroplasias well supported by the expression of transforming growth factor
      alpha, endothelial nitric oxide synthase (eNOS) and fibroblast growth factor.
      Upregulation of interleukin 6 in DRDE/WH-02-treated mice skin resulted in
      increased tissue leukocytosis and an early removal of tissue debris that
      initiated reparative process at faster rate compared to other groups. In
      conclusion, DRDE/WH-02 provided better healing effect and can be recommended as
      an effective wound healant against SM-induced skin injury.

PMID- 22144727
TI  - Statins lower calcium-induced oxidative stress in isolated mitochondria.
AB  - Statins are widely used cholesterol-lowering agents that exert cholesterol
      independent effects including antioxidative. The present study delineates the
      effects of statins, atorvastatin, and simvastatin on oxidative stress and
      functions of mitochondria that are the primary cellular sources of oxidative
      stress. In isolated rat liver mitochondria, both the statins prevented calcium
      induced cytochrome c release, lipid peroxidation, and opening of the
      mitochondrial membrane permeability transition (MPT). Both the statins decreased
      the activity of mitochondrial nitric oxide synthase (mtNOS), lowered the
      intramitochondrial ionized calcium, and increased the mitochondrial transmembrane
      potential. Our findings suggest that statins lower intramitochondrial ionized
      calcium that decreases mtNOS activity, lowers oxidative stress, prevents MPT
      opening, and prevents the release of cytochrome c from the mitochondria. These
      results provide a novel framework for understanding the antioxidative properties
      of statins and their effects on mitochondrial functions.

PMID- 22144728
TI  - Possible prenatal impact of sertraline on human placental glutathione S
      transferase-pi.
AB  - Sertraline (SER), a tricyclic antidepressant, is considered to belong to the
      group of selective amine reuptake inhibitors. Its ability to cross the blood
      brain barrier and transplacental transport has been reported previously. It is
      widely distributed in the brain and is bound to human glutathione S-transferase
      pi (GST-pi). If SER is taken during pregnancy, it gets accumulated in the embryo
      and fetus, and some studies have suggested it may cause congenital malformations,
      thus the study of the interaction of GST-pi with antidepressants is crucial. In
      this study, the interaction of human placental GST-pi with SER in the presence of
      the natural ligand, reduced glutathione (GSH) and a xenobiotic ligand, 1-chloro
      2,4-dinitrobenzene (CDNB) was investigated. The V(m) values obtained at variable
      [CDNB] and variable [GSH] were 61.3 +/- 2.3 and 46.4 +/- 1.7 U/mg protein,
      respectively. The k(cat) and k(cat)/K(m) values for GSH and CDNB were 3.63 *
      10(6) s(-1), 2.59 * 10(10) M(-1) s(-1) and 4.79 * 10(6) s(-1), 1.29 * 10(10) M(
      1) s(-1), respectively. The half maximal inhibitory concentration value for SER
      was 4.60 mM. At constant [CDNB] and variable [GSH] the inhibition type was linear
      mixed-type, with K(s), alpha, and K(i) values of 0.14 +/- 0.02, 2.90 +/- 1.64,
      and 2.18 +/- 0.80 mM, respectively. On the other hand, at fixed [GSH] and at
      variable [CDNB], the inhibition type was competitive, with K(i) value of 0.96 +/-
      0.10 mM. Thus, these findings weaken the importance of the protective role of GST
      against toxic electrophiles in vivo in adults, but due to its immature
      enterohepatic system SER may accumulate in the fetus and cause congenital
      malformations.

PMID- 22144729
TI  - Long-acting phosphodiesterase 5 inhibitor, tadalafil, and superoxide dismutase
      mimetic, tempol, protect against acute hypoxia-induced pulmonary hypertension in
      rats.
AB  - Long-acting phosphodiesterase 5 (PDE5) inhibitor, tadalafil, was recently
      approved for the treatment of pulmonary hypertension. Apart from being a PDE5
      inhibitor, tadalafil also possesses antioxidant activity. The aim of this study
      was to probe whether tadalafil has any beneficial effect over tempol owing to its
      antioxidant action in addition to PDE5 inhibitory activity. Albino Wistar rats
      were pretreated with tadalafil (10 mg/kg) or vehicle 2 h before hypoxic exposure,
      whereas tempol (20 mg/kg) was given 5 min before induction of hypoxia. Right
      ventricular systolic pressure (RVSP), mean arterial pressure (MAP), heart rate
      (HR), right ventricular contractility (RVdP/dtmax) and cardiac output (CO) were
      recorded while subjecting rats to acute hypoxia for 30 min. Lipid peroxidation
      and reduced glutathione were estimated in serum before and after hypoxia
      exposure. Tadalafil as well as tempol significantly prevented hypoxia-induced
      rise in RVSP (p < 0.001) and RVdP/dtmax (p < 0.05). Both tadalafil and tempol
      pretreatment partially prevented (p < 0.01) the rise in CO due to hypoxia.
      Tadalafil did not produce any significant change in MAP, whereas tempol led to a
      significant fall (p < 0.01) in MAP. Acute hypoxia increased the oxidative stress
      levels. Tadalafil pretreatment partially prevented hypoxia-induced oxidative
      stress, while tempol pretreatment completely prevented hypoxia-induced oxidative
      stress. Results suggest that tadalafil because of its antioxidant action in
      addition to PDE5 inhibitory activity is more appropriate for the prevention of
      hypoxic pulmonary hypertension than tempol. Tempol also produced undesirable
      systemic hypotension as side effect, which was not seen with tadalafil because of
      its pulmonary selective action.

PMID- 22144732
TI  - Trajectories of social engagement and limitations in late life.
AB  - Although studies have established important links between social relations and
      health, much of this research does not take into account the dynamic nature of
      both social relations and health over time. The present study combines person
      centered and variable-centered approaches and uses social integration theory
      within the life course framework to examine patterns of change in social
      engagement and how those patterns relate to trajectories of physical and
      cognitive limitations among older adults, using data from the Americans' Changing
      Lives survey, a nationally representative panel study (N = 1,667). Individuals
      who had trajectories of high and increasing social engagement experienced lower
      levels of physical and cognitive limitations over time. The findings suggest the
      importance of maintaining high levels of social engagement for the physical and
      cognitive health of older adults.

PMID- 22144731
TI  - Changing work, changing health: can real work-time flexibility promote health
      behaviors and well-being?
AB  - This article investigates a change in the structuring of work time, using a
      natural experiment to test whether participation in a corporate initiative
      (Results Only Work Environment; ROWE) predicts corresponding changes in health
      related outcomes. Drawing on job strain and stress process models, we theorize
      greater schedule control and reduced work-family conflict as key mechanisms
      linking this initiative with health outcomes. Longitudinal survey data from 659
      employees at a corporate headquarters shows that ROWE predicts changes in health
      related behaviors, including almost an extra hour of sleep on work nights.
      Increasing employees' schedule control and reducing their work-family conflict
      are key mechanisms linking the ROWE innovation with changes in employees' health
      behaviors; they also predict changes in well-being measures, providing indirect
      links between ROWE and well-being. This study demonstrates that organizational
      changes in the structuring of time can promote employee wellness, particularly in
      terms of prevention behaviors.

PMID- 22144733
TI  - The labeling paradox: stigma, the sick role, and social networks in mental
      illness.
AB  - Although research supports the stigma and labeling perspective, empirical
      evidence also indicates that a social safety net remains intact for those with
      mental illness, recalling the classic "sick role" concept. Here, insights from
      social networks theory are offered as explanation for these discrepant findings.
      Using data from individuals experiencing their first contact with the mental
      health treatment system, the effects of diagnosis and symptoms on social networks
      and stigma experiences are examined. The findings suggest that relative to those
      with less severe affective disorders, individuals with severe diagnoses and more
      visible symptoms of mental illness have larger, more broadly functional networks,
      as well as more supporters who are aware of and sympathetic toward the illness
      situation. However, those with more severe diagnoses are also vulnerable to
      rejection and discrimination by acquaintances and strangers. These findings
      suggest that being formally labeled with a mental illness may present a paradox,
      simultaneously initiating beneficial social processes within core networks and
      detrimental ones among peripheral ties.

PMID- 22144734
TI  - Health care segregation and race disparities in infectious disease: the case of
      nursing homes and seasonal influenza vaccinations.
AB  - Examining nursing home segregation and race disparities in influenza
      vaccinations, this study demonstrates that segregation may increase both
      susceptibility and exposure to seasonal flu for black Americans. Evidence based
      on the 2004 U.S. National Nursing Home Survey shows that individuals in nursing
      homes with high percentages of black residents have less personal immunity to flu
      because they are less likely to have been vaccinated against the disease; they
      may also be more likely to be exposed to flu because more of their coresidents
      are also unvaccinated. This implies that segregation may generate dual disease
      hazards for contagious conditions. Segregation appears to limit black Americans'
      access to personal preventive measures against infection, while spatially
      concentrating those people who are most likely to become contagious.

PMID- 22144737
TI  - Antimetastatic potentials of Phyllanthus urinaria L on A549 and Lewis lung
      carcinoma cells via repression of matrix-degrading proteases.
AB  - Tumor metastasis is the most important cause of cancer death and various
      treatment strategies have targeted at preventing the occurrence of metastasis.
      Phyllanthus urinaria L is a popular folk medicine and has several proven
      biological properties, including antioxidant, antihypertension, and anti
      inflammatory. This study provides molecular evidence associated with the
      antimetastatic effects of P urinaria L extracts (PUE), which contained
      polyphenols including gallic acid, methyl gallate, epicatechin, epigallocatechin
      3-gallate, gallocatechin-3-gallate, rutin, epicatechin-3-gallate, and naringin,
      by showing a marked inhibition on the invasion (P < .001) and migration (P <
      .001) of highly metastatic A549 and Lewis lung carcinoma (LLC) cells. To further
      investigate the precise involvement of PUE in tumor metastasis, A549 and LLC
      cells were treated with PUE at various concentrations and results from zymography
      and Western blotting showed that a PUE treatment may decrease the expressions of
      matrix metalloproteinase-2 (MMP-2; P < .001), MMP-9 (P < .001), urokinase
      plasminogen activator (P < .001), and their endogenous inhibitors, that is,
      tissue inhibitor of metalloproteinase-2 and plasminogen activator inhibitor-1, in
      a concentration-dependent manner. Reverse transcription-polymerase chain reaction
      and MMP-2 promoter luciferase analysis (P < .001) revealed that PUE inhibits the
      transcription of MMP-2 mRNA. PUE also exerted an inhibitory effect on the DNA
      binding activity and the nuclear translocation of NF-kappaB and AP-1.
      Furthermore, the inhibitory effects of PUE on the metastasis and growth of LLC
      cells in vivo were proven. These results indicate that PUE could be applied to be
      a potential antimetastatic agent.

PMID- 22144738
TI  - New technologies for the enhancement of skeletal repair: Challenges and
      opportunities.

PMID- 22144739
TI  - Comparison of one-stage anteroposterior and posterior-alone hemivertebrae
      resection combined with posterior correction for hemivertebrae deformity.
AB  - BACKGROUND: The surgical technique of hemivertebrae excision varies from
      anteroposterior procedures to posterior-alone resections according to the
      experience and preference of surgeons. Both the approaches are reliable and give
      relatively good results. This study aims to evaluate and compare the clinical and
      radiological results of these two approaches for hemivertebrae resection.
      MATERIALS AND METHODS: Sixty patients were retrospectively enrolled between 2006
      and 2009. The subjects included 32 women and 28 men, with a mean age of 12.9
      years (range: 5-24 years). Thirty patients who underwent one-stage
      anteroposterior hemivertebrae resection (the AP group) were followed for 38.5
      months, and the other 30 patients who underwent posterior resection (the P group)
      were followed for 20.6 months. Clinical and radiological assessments were
      performed preoperatively, 1 week postoperatively, and at the final follow-up. The
      operation time, blood loss, degree of correction of the main curve/segmental
      curve/kyphosis, the average hospital stay, and complications were reviewed and
      compared between the two groups. RESULTS: The mean operation time, blood loss,
      and hospital stay of the AP group and the P group were 451 min vs 248.5 min, 1290
      ml vs 910 ml, and 21.93 days vs 18.97 days, respectively (P<.05). The average
      correction rate of the main curve/segmental curve/kyphosis of the AP group and
      the P group was 68.5% vs 66.2%, 71.5% vs 69.6%, and 57.4% vs 56.1%, respectively
      (P>.05). Overall complication rate was 6.7% in the AP group vs 10% in the P group
      (P>.05). CONCLUSION: Posterior hemivertebrael resection is a promising approach
      for congenital scoliosis in terms of relative safety, degree of correction
      achieved, reduced operative time and blood loss.

PMID- 22144740
TI  - Erratum: ERRATUM.
AB  - [This corrects the article on p. 347 in vol. 45, PMID: 21772629.].

PMID- 22144741
TI  - Outcome of single level instrumented posterior lumbar interbody fusion using
      corticocancellous laminectomy bone chips.
AB  - BACKGROUND: Interbody fusion surgery has been considered by many to be a
      treatment of choice for instability in lumbar degenerative disc disease. A
      posterior lumbar interbody fusion (PLIF) has the advantages of spinal canal
      decompression, anterior column reconstruction, and reduction of the sagittal
      slips from a single posterior approach. The PLIF using double cage was a standard
      practice till many studies reported comparable results and lesser complications
      with single cage. Iliac crest was considered as an appropriate source of bone
      graft until comparable spinal fusion rates using local bone graft and cage
      emerged. Till date, there has been no report of corticocancellous laminectomy
      bone chips alone being used for spinal fusion. In this paper, we present
      radiologic results of single level instrumented PLIF, where in only
      corticocancellous laminectomy bone chips were used as a fusion device. MATERIALS
      AND METHODS: It is a retrospective cohort study of 35 consecutive patients, who
      underwent single level instrumented PLIF surgery, wherein only locally obtained
      bone chips was used for spinal fusion. The average follow-up was 26 months. The
      indications for the surgery were as follows: 19 patients had disc herniations,
      with back pain of instability type, normal disc height on radiology. Ten patients
      had grade 1 spondylolisthesis, with significant back pain and translational
      instability on radiography. Three patients were redo spine surgeries, and three
      patients had healed spondylodiscitis with significant back pain and instability.
      All patients were regularly followed up and decision of spinal fusion or no
      fusion was taken at 2 years using modified criteria of Lee. RESULTS: Of total 35
      patients, there were 24 males and 11 females, with a mean age of 41 years. There
      were 16 patients with definitive fusion, 15 patients with probable fusion, 04
      patients with possible pseudoarthrosis, and no patient had definitive
      pseudoarthrosis. The mean time for fusion to occur was 18 months. The average
      loss of disc height, over 2 year follow up, was only 3 mm in 8 patients. Three
      patients had a localized kyphosis of more than 3 degrees  at the fusion level.
      The average blood loss was 356 ml and average operating time was 150 min.
      CONCLUSION: Corticocancellous laminectomy bone chips alone can be used as a means
      of spinal fusion in patients with single level instrumented PLIF. This has got a
      good fusion rate.

PMID- 22144742
TI  - Radiological assessment of cervical lateral mass screw angulations in Asian
      patients.
AB  - BACKGROUND: Various lateral mass screw fixation methods have been described in
      the literature with various levels of safety in relation to the anterior
      neurovascular structures. This study was designed to radiologically determine the
      minimum lateral angulations of the screw to avoid penetration of the vertebral
      artery canalusing three of the most common techniques: Roy-Camille, An, and
      Magerl. MATERIALS AND METHODS: Sixty normal cervical CT scans were reviewed. A
      minimum lateral angulation of a 3.5 mm lateral mass screw which was required to
      avoid penetration of the vertebral artery canal at each level of vertebra were
      measured. RESULTS: The mean lateral angulations of the lateral mass screws (with
      95% confidence interval) to avoid vertebral artery canal penetration, in relation
      to the starting point at the midpoint (Roy-Camille), 1 mm medial (An), and 2 mm
      medial (Magerl) to the midpoint of lateral mass were 6.8 degrees  (range, 6.3-7.4
      degrees ), 10.3 degrees  (range, 9.8-10.8 degrees ), and 14.1 degrees  (range,
      13.6-14.6 degrees ) at C3 vertebrae; 6.8 degrees  (range, 6.2-7.5 degrees ), 10.7
      degrees  (range, 10.0-11.5 degrees ), and 14.1 degrees  (range, 13.4-14.8 degrees
      ) at C4 vertebrae; 6.6 degrees  (range, 6.0-7.2 degrees ), 10.1 degrees  (range,
      9.3-10.8 degrees ), and 13.5 degrees  (range, 12.8-14.3 degrees ) at C5 vertebrae
      and 7.6 degrees  (range, 6.9-8.3 degrees ), 10.9 degrees  (range, 10.3-11.6
      degrees ), and 14.3 degrees  (range, 13.7-15.0 degrees ) at C6 vertebrae. The
      recommended lateral angulations for Roy-Camille, Magerl, and An are 10 degrees ,
      25 degrees ,and 30 degrees , respectively. Statistically, there is a higher risk
      of vertebral foramen violation with the Roy-Camille technique at C3, C4 and C6
      levels, P < 0.05. CONCLUSIONS: Magerl and An techniques have a wide margin of
      safety. Caution should be practised with Roy-Camille's technique at C3, C4, and
      C6 levels to avoid vertebral vessels injury in Asian population.

PMID- 22144743
TI  - Bicentric bipolar hip prosthesis: A radiological study of movement at the
      interprosthetic joint.
AB  - BACKGROUND: The bipolar hip prostheses after some time functions as a unipolar
      device. There is a need to change the design of bipolar hip prostheses to make it
      function as a bipolar device over a prolonged period of time. A bicentric bipolar
      hip prosthesis was used as an implant for various conditions of the hip. We
      evaluated the movement of this newly developed prosthesis at the interprosthetic
      joint radiologically at periodic intervals. MATERIALS AND METHODS: Fifty two
      cases were operarted with the Bicentric bipolar prosthesis for indications like
      fracture neck of femur and various other diseases of the hip and were followed up
      with serial radiographs at periodic intervals to evaluate, what fraction of the
      total abduction at the hip was occurring at the interprosthetic joint. RESULTS:
      In cases of intracapsular fracture neck of femur, the percentage of total
      abduction occurring at the interprosthetic joint at 3 months follow-up was 33.74%
      (mean value of all the patients), which fell to 25.66% at 1.5 years. In
      indications for bipolar hemireplacement other than fracture neck of femur, the
      percentage of total abduction occurring at the interprosthetic joint at 3 months
      follow-up was 71.71% (mean value) and at 1.5 years it was 67.52%. CONCLUSION:
      This study shows the relative preservation of inner bearing movement in the
      bipolar hip prosthesis with time probably due its refined design. Further
      refinements are needed to make the prosthesis work better in patients of
      intracapsular fracture neck femur.

PMID- 22144744
TI  - Primary nonunion of intertrochanteric fractures of femur: An analysis of results
      of valgization and bone grafting.
AB  - BACKGROUND: Nonunion of intertrochanteric fractures is uncommon because there is
      excellent blood supply and good cancellous bone in the intertrochanteric region
      of the femur. A diagnosis of primary intertrochanteric nonunion is made when at
      least 15 weeks after the fracture there is radiological evidence of a fracture
      line, with either no callus (atrophic) or with callus that does not bridge the
      fracture site (hypertrophic). There is only one published series that exclusively
      describes seven primary nonunions of intertrochanteric fractures. The aim of the
      present study was to analyze the results of internal fixation, valgization with
      135 degrees  dynamic hip screw (DHS), and bone grafting in patients with primary
      nonunion of intertrochanteric fractures. MATERIALS AND METHODS: Eighteen patients
      with primary intertrochanteric nonunion were included in the study; 16 were male
      and 2 were female. The age range was 30-70 years (mean: 46.9 years). The mean
      duration since index injury was 8.5 months (range: 4-18 months). As per the AO
      classification, the fractures were 31A 1.1 (n=1), 1.2 (n=1), 2.2 (n=3), 2.3
      (n=9), and 3.3 (n=4). Three patients had hypermobile nonunion and 15 had stiff
      nonunion. The surgical principle was excision of pseudarthrosis, if present
      (n=3); freshening of the bone ends; stable fixation with 135 degrees  DHS, with
      good proximal purchase; bone grafting; and valgization. RESULTS: Union was
      achieved in all patients at an average of 5.62 months (range: 4-7 months). The
      Harris hip score improved from 38 points preoperatively to 86 postoperatively at
      healing. The average limb shortening improved by 2 cm (range: 1.5 cm-3 cm). There
      was no infection and pain at the hip at final follow-up in any of the cases. All
      patients were subjectively satisfied with the outcome. All were capable of full
      weight bearing on their affected limb. CONCLUSION: Union in primary nonunion of
      intertrochanteric fractures in physiologically young patients with a well
      preserved femoral head and good bone stock can be achieved with internal
      fixation, valgization, and grafting procedures.

PMID- 22144745
TI  - Minimally invasive plate osteosynthesis for humerus diaphyseal fractures.
AB  - BACKGROUND: Minimally invasive plate osteosynthesis (MIPO) technique is reported
      as a satisfactory procedure for the treatment of humeral shaft fractures by the
      anterior approach by several authors. However, none of the published reports had
      a significant follow-up nor have they reported patient outcomes. We evaluated the
      clinical, radiographic, and functional outcome over a minimum follow-up of 2
      years using the same MIPO technique to humeral shaft fracture. MATERIALS AND
      METHODS: 32 adult patients with diaphyseal fractures of the humerus treated with
      MIPO between June 2007 and October 2008 were included in the study. Patients with
      metabolic bone disease, polytrauma, and Gustilo and Anderson type 3 open
      fractures with injury severity score >16 were excluded from the study. All cases
      were treated with closed indirect reduction and locking plate fixation using the
      MIPO technique. The surgery time, radiation exposure, and time for union was
      noted. The shoulder and elbow function was assessed using the UCLA shoulder and
      Mayo elbow performance scores, respectively. RESULTS: Of the 32 patients in the
      study, 19 were males and 13 were females. The mean age was 39 years (range: 22-70
      years). Twenty-seven of the thirty-two patients (84.3%) had the dominant side
      fractured. We had eight cases of C2 type; five cases of C1 and A2 type; four
      cases of B2 type; three cases each of B3, B1, and A1 type; and one case of A3
      type of fracture. The mean surgical time was 91.5 minutes (range: 70-120 minutes)
      and mean radiation exposure was 160.3 seconds (range: 100-220 seconds). The mean
      radiological fracture union time was 12.9 weeks (range: 10-20 weeks). Shoulder
      function was excellent in 27 cases (84.3%) and good in remaining 5 cases (15.6%)
      on the UCLA score. Elbow function was excellent in 26 cases (81.2%), good in 5
      cases (15.6%), and fair in 1 case (3.1%) who had an associated olecranon fracture
      that was fixed by tension band wire in the same sitting. CONCLUSION: MIPO of the
      humerus gives good functional and cosmetic results and should be considered one
      of the management options in the treatment of humeral diaphyseal fractures.

PMID- 22144746
TI  - Dynamic vs static external fixation of distal radial fractures: A randomized
      study.
AB  - OBJECTIVES: The present randomized study is conducted to compare the functional
      and anatomical outcomes of dynamic multiplanar external fixation against that of
      static external fixation in the management of displaced unstable comminuted
      fractures of the distal radius. MATERIALS AND METHODS: Sixty adult patients with
      displaced unstable comminuted fractures of the distal radius were randomly
      allocated either to the dynamic (n=30) or static (n=30) fixator groups. Patients
      in the dynamic fixator group were managed with closed reduction and application
      of Penning-type articulated fixator (Orthofix, Srl, Italy); the injured wrist was
      partially dynamized at 3 weeks. Patients in the static group were managed with
      monoplanar static external fixator of Joshi's external stabilizing system (JESS)
      type fixator. In both groups, the fixator was maintained for 6-8 weeks. The
      patients were followed-up over 2 years. The primary outcome measures were the
      functional outcome as measured using the Gartland and Werley and DASH scores and
      anatomical outcome as measured using the Lindstrom score. The secondary objective
      was to correlate anatomical and functional outcomes and to look at overall local
      complications. RESULTS: Palmar tilt was better restored in the Penning fixator
      group (P<0.0001). There was reduced loss of ulnar tilt (P=0.05) and radial height
      (P=0.04) in the Penning fixator group. Gartland and Werley score was better in
      the Penning fixator group at each time point of the follow-up. The DASH score was
      similar in the two groups at 2 years (P=0.14). There was poor correlation (0.19)
      between functional outcome and anatomical restoration at 2 years. CONCLUSIONS: In
      the management of displaced unstable comminuted fracture of the distal radius,
      use of an articulated multiplanar external fixator, allowing partial dynamization
      of the injured wrist at 3 weeks, resulted in improved early functional and
      anatomical outcome as compared to static external fixation. However, there was no
      significant difference in functional outcome at 2 years.

PMID- 22144747
TI  - Antibiotic-impregnated articulating cement spacer for infected total knee
      arthroplasty.
AB  - BACKGROUND: Standard treatment of chronic infected total knee arthroplasty (TKA)
      is a two-stage revision, the first step being placement of an antibiotic
      impregnated cement spacer. Here we describe the results of a new technique
      (modification of the Goldstien's technique) for intraoperative manufacture of a
      customized articulating spacer at minimal cost and with relatively good
      conformity and longevity. MATERIALS AND METHODS: Thirty-six infected knees
      underwent this procedure from June 2002 to May 2007. The technique consists of
      using the freshened femur and tibia interface as molds wrapped in a tin foil for
      manufacturing the two components of the spacer with antibiotic-impregnated methyl
      methycrylate cement. We used the spacer and the femoral component of the trial
      set of a TKA system to mold them to perfect articulation. We also reinforced the
      spacer with a K-wire scaffold to prevent fracture of the cement mantle in the
      last 21 cases. RESULTS: All 36 knees showed excellent results in terms of
      infection control, mobility, and stability. There was significant improvement in
      the WOMAC and Knee Society Scores (20 and 39 points respectively). There were two
      fractures of the spacers in the initial 15 cases that did not have K-wire
      scaffolding but none in the last 21 that had reinforcement. CONCLUSION: This
      technique provides a more conforming spacer, with good range of motion and
      stability. The reinforcement helps in preventing the fracture of the cement
      mantle and is cost effective.

PMID- 22144748
TI  - Salvage of infected total knee arthroplasty with Ilizarov external fixator.
AB  - BACKGROUND: Knee arthrodesis may be the only option of treatment in cases of
      chronic infected total knee arthroplasty (TKA) with concomitant irreparable
      extensor mechanism disruption, extensive bone loss or severe systemic
      morbidities. Circular external fixation offers possible progressive adjustment to
      stimulate the bony fusion and to make corrections in alignment. We evaluated the
      results of knee arthrodesis with one or two stage circular external fixator for
      infected TKA. MATERIALS AND METHODS: 16 cases of femoro-tibial fusion were
      retrospectively evaluated. Male-to-female ratio was 10:6. Mean age of the
      patients was 62.2 years. Cierney-Mader classification was used for anatomical and
      physiological evaluation while the bone stock deficiency was classified into
      mild, moderate and severe. Surgical technique involved either single or two stage
      arthrodesis using circular external fixator. RESULTS: Union was achieved in 15
      patients (93.75%). The mean duration for union (frame application time) in these
      patients was 28.33 weeks (range 22 to 36 weeks). Analysis showed that in the
      group with frame application time of less than 28 weeks, the incidence of mild to
      moderate bone deficiency was 83.33%, while in the frame application time more
      than 28 weeks group the incidence was 20% (P-value 0.034). Similarly the
      incidence of Cierney-Mader 4B (Bl, Bs, Bls) was found to be 33.33% in the group
      of frame application time of less than 28 weeks, while it was 90% in the group
      with frame application time more than 28 weeks (P-value 0.035). CONCLUSION:
      Circular external fixator is a safe and reliable method to achieve knee
      arthrodesis in cases of deep infection following TKA. Severe bone stock
      deficiency and Cierney- Mader type B host are likely risk factors for prolonged
      frame application time. We recommend a two-stage procedure especially when there
      is compromised host or severe bone loss.

PMID- 22144749
TI  - Utility of combined hip abduction angle for hip surveillance in children with
      cerebral palsy.
AB  - BACKGROUND: Spontaneous hip lateralization complicates the management of non
      ambulatory children with cerebral palsy (CP). It can be diagnosed early using
      radiographs, but it involves standardization of positioning and exposure to
      radiation. Hence, the aim of this study was to assess the utility of Combined hip
      abduction angle (CHAA) in the clinical setting to identify those children with CP
      who were at greater risk to develop spontaneous progressive hip lateralization.
      MATERIALS AND METHODS: One hundred and three children (206 hips) with CP formed
      our study population. There were 48 boys and 55 girls aged 2-11 years (mean 5.03
      years). 61 children were Gross Motor Function Classification System (GMFCS) level
      5, while 42 were GMFCS level 4. Clinical measurements of CHAA were statistically
      correlated with radiographic measurements of Reimer's migration percentage (MP)
      for bivariate associations using chi(2) and t tests. RESULTS: CHAA is evaluated
      against MP which is considered as a reliable measure of hip subluxation. Thus,
      for CHAA, sensitivity was 74.07% and specificity was 67.35%. False-positive rate
      was 32.65% and false-negative rate was 25.93%. CONCLUSIONS: Our study shows that
      correlation exists between CHAA and MP, which has been proved to be useful for
      hip screening in CP children at risk of hip dislocation. CHAA is an easy, rapid,
      cost-effective clinical test which can be performed by paraclinical health
      practitioners (physiotherapists) and orthopedic surgeons.

PMID- 22144750
TI  - Reliability of ultrasonographic measurements in suspected patients of
      developmental dysplasia of the hip and correlation with the acetabular index.
AB  - BACKGROUND: Ultrasonography is accepted as a useful imaging modality in the early
      detection of developmental dysplasia of the hip (DDH). Early detection and early
      treatment of DDH prevents hip dislocation and related physical, social, economic,
      and psychological problems. The purpose of this study was to evaluate the
      reliability of ultrasonographic and roentgenographic measurements measured by
      seven different observers. MATERIALS AND METHODS: The alpha angles of 66 hips in
      33 patients were measured using the Graf method by seven different observers.
      Acetabular index degrees on plane roentgenograms were measured in order to assess
      the correlation between the ultrasonographic alpha angle and the radiographic
      acetabular index, which both show the bony acetabular depth, retrospectively.
      RESULTS: The interclass correlation coefficient, measuring the interobserver
      reliability, was high and statistically significant for the ultrasonographic
      measurements. There was a negative correlation between the alpha angle and the
      acetabular index. CONCLUSIONS: Ultrasonography, when applied properly, is a
      reliable technique between different observers, in the diagnosis and follow up of
      DDH. When assessed concomitantly with the roentgenographic measurements, the
      results are reliable and statistically meaningful.

PMID- 22144751
TI  - Outcome of tendon transfer for radial nerve paralysis: Comparison of three
      methods.
AB  - BACKGROUND: Tendon transfer for radial nerve paralysis has a 100 years history
      and any set of tendons that can be considered to be useful has been utilized for
      the purpose. The pronator tress is used for restoration of wrist dorsiflexion,
      while the flexor carpi radialis, flexor carpiulnaris, and flexor digitorum
      superficialis are variably used in each for fingers and thumb movements. The
      present study was a retrospective analysis, designed to compare three methods of
      tendon transfer for radial nerve palsy. MATERIALS AND METHODS: 41 patients with
      irreversible radial nerve paralysis, who had underwent three different types of
      tendon transfers (using different tendons for transfer) between March 2005 and
      September 2009, included in the study. The pronator teres was transferred for
      wrist extention. Flexor carpi ulnaris (group 1, n=18), flexor carpi radialis
      (group 2, n=10) and flexor digitorum superficialis (group 3, n=13) was used to
      achieve finger extention. Palmaris longus was used to achieve thumb extention and
      abduction. At the final examination, related ranges of motions were recorded and
      the patients were asked about their overall satisfaction with the operation,
      their ability, and time of return to their previous jobs, and in addition,
      disabilities of the arm, shoulder and hand (DASH) Score was measured and recorded
      for each patient. RESULTS: The difference between the groups with regard to DASH
      score, ability, and time of return to job, satisfaction with the operation, and
      range of motions was not statistically significant (P>0.05). All of the patients
      had experienced functional improvement and overall satisfaction rate was 95%. No
      complication directly attributable to the operation was noted, except for
      proximal interphalangeal joint flexion contracture in three patents. CONCLUSION:
      The tendon transfer for irreversible radial nerve palsy is very successful and
      probably the success is not related to type of tendon used for transfer.

PMID- 22144752
TI  - Arterio-venous fistula following a lumbar disc surgery.
AB  - Vascular complications during posterior lumbar disc surgery are rare and its
      presentation with varicose veins is even rarer. A 23 year-old male patient
      presented with large varicose veins in right lower limb. He underwent a posterior
      lumbar spine discectomy surgery. He noticed mild swelling of the distal third
      right lower limb 3 months after index surgery and reported 6 months later when he
      developed varicose veins. Duplex Doppler confirmed varicose veins of the long
      saphenous vein and its tributaries with a patent deep venous system. A digital
      subtraction angiogram demonstrated a large right common iliac artery (CIA) false
      aneurysm with an arteriovenous fistula between right common iliac vessels. He had
      a right CIA covered stent insertion with good results. Varicose veins were later
      managed with sapheno-femoral junction ligation and a below knee long saphenous
      vein stripping. At six month follow-up the lower limb swelling had completely
      recovered and duplex ultrasound did not show any recurrence of varicose veins.

PMID- 22144753
TI  - Gorham's disease of femur.
AB  - Gorham's disease is a rare condition of bones characterized by spontaneous
      massive and progressive osteolysis. Less than 200 cases have been reported so
      far. Femur is an uncommon site of Gorham disease. We report a young female,
      presenting as pathological fracture of the femur, wherein rapid osteolysis of
      femur occurred. The clinical, pathological, and radiological picture suggested a
      diagnosis of Gorham's disease. The patient was subjected to radiotherapy (40 Gys)
      and put on bisphosphonates. At a follow-up of 2 years, the disease process had
      stopped and partial recalcification of the bone had occurred.

PMID- 22144754
TI  - Hydroxyapatite crystal deposition causing rapidly destructive arthropathy of the
      hip joint.
AB  - Destructive arthropathy of the hip joint can be attributed to various etiologies
      like rheumatoid arthritis, aseptic necrosis of the femur head, Charcot's joint,
      subacute septic arthritis, and tubercular arthritis. A disease that results in
      much rapid destruction of the hip joint and is not associated with clinical
      syndrome of above mentioned disease has been reported way back in 1970. However,
      no evidence-based study has been published to support hydroxyapatite (HA)
      crystals as a probable cause of rapidly destructive arthropathy of the hip joint.
      We report a case with microscopic and biochemical confirmation of HA crystal
      deposition causing destructive arthropathy of the hip joint.

PMID- 22144755
TI  - Myositis ossificans around shoulder following military training programme.
AB  - The myositis ossificans around shoulder in military recruits are not reported
      yet. Three young male soldiers presented with complaints of palpable mass at the
      anterior aspect of shoulder; tenderness around the superior part of deltopectoral
      groove close to acromioclavicular joint; and restriction of shoulder motion. They
      also noticed ecchymosis and pain around the coracoid process and anterior
      shoulder region during regular firing exercises. Plain X-rays and computerized
      tomography showed extra-capsular, dense, irregular structure in the space between
      pectoralis and deltoid muscles which correlated with heterotopic bone. One
      patient refused surgical intervention because of the completion of his military
      serving period. Surgical excision was performed for the other two patients.
      During surgical exploration, both ossified masses were found in deltopectoral
      region and mostly in fibers of clavicular and acromial parts of deltoid muscle.
      Pathological reports confirmed the structure of masses as mature trabecular bone.
      Postoperatively indomethacin treatment and active shoulder exercises were started
      until the full range of motion was regained. Mini soft bag was used on the rifle
      contact area of the shoulder. No complications or recurrences were observed
      during the 24 months of followup period.

PMID- 22144756
TI  - Complex multilevel lumbar spine fractures with transverse sacral fracture.
AB  - We report an unusual and complex case of spinal trauma in a 17-year-old boy who
      presented with a transverse sacral fracture associated with multiple-level lumbar
      fractures, paraparesis, and bladder involvement. A two-stage surgery was
      performed. The lumbar spine fractures were treated with posterior instrumented
      correction of displacements, followed by anterior instrumentation and fusion. The
      sacral fracture was left untreated. At 5-year followup, the patient had complete
      neurological recovery except for the right L5 root function. The long-segment
      lumbar fusion and the untreated displaced sacral fracture contributed to spinal
      imbalance, due to which the patient is now able to stand only in a crouched
      posture. Determining the optimal treatment for the case is presented due to the
      relative rarity of transverse sacral fracture and paucity of evidence-based
      treatment approaches. In patients with associated lumbar spine fractures that
      require extension of instrumentation to the upper lumbar spine, it is critical to
      restore sacropelvic alignment to achieve spinal balance. Adequate reduction of
      sacropelvic anatomy can be achieved with iliac screw fixation.

PMID- 22144757
TI  - Tranexamic acid for control of blood loss in bilateral total knee replacement in
      a single stage.

PMID- 22144758
TI  - Authors' reply.

PMID- 22144759
TI  - Femoral tunnel-interference screw divergence in anterior cruciate ligament
      reconstruction using bone-patellar tendon-bone graft: A comparison of two
      techniques.

PMID- 22144760
TI  - Authors' reply.

PMID- 22144761
TI  - Indian Pharmacological Society: A SWOT analysis.

PMID- 22144762
TI  - Vitamin-C as anti-Helicobacter pylori agent: More prophylactic than curative-
      Critical review.
AB  - Potential of nonantibiotic therapies for treatment of Helicobacter pylori-related
      acid peptic disease remains underexplored. Several clinical studies have shown
      that higher prevalence of H. pylori infection is associated with low Vitamin C
      (Vit C) level in serum and gastric juice. However, there is no consensus
      regarding the usefulness of Vit C supplementation in the management of H. pylori
      infection. Surveying the existing literature we conclude that high concentration
      of Vit C in gastric juice might inactivate H. pylori urease, the key enzyme for
      the pathogen's survival and colonization into acidic stomach. Once infection
      established, urease is not very important for its survival. The role of Vit-C as
      anti-H. pylori agent in peptic ulcer diseases appears to be preventive rather
      than curative. Rather than supplementing high dose of Vit C along with
      conventional triple therapy, it is preferable to complete the conventional
      therapy and thereafter start Vit C supplementation for extended period which
      would prevent reinfection in susceptible individuals, provided the patients are
      not achlorhydric. Further studies are required to prove the role of Vit C in
      susceptible population.

PMID- 22144763
TI  - Efficacy and safety of topical nadifloxacin and benzoyl peroxide versus
      clindamycin and benzoyl peroxide in acne vulgaris: A randomized controlled trial.
AB  - BACKGROUND: Topical therapy with comedolytics and antibiotics are often advocated
      for mild and moderate severity acne vulgaris. Nadifloxacin, a new fluoroquinolone
      with anti-Propionibacterium acnes activity and additional anti-inflammatory
      activity, is approved for use in acne. This randomized controlled assessor blind
      trial compared the clinical effectiveness and safety of eight weeks therapy of
      nadifloxacin 1% versus clindamycin 1% as add-on therapy to benzoyl peroxide
      (2.5%) in mild to moderate grade acne. MATERIALS AND METHODS: The efficacy
      parameters were changes in the total, inflammatory and non-inflammatory lesion
      counts, Investigator Global Assessment (IGA), and Cardiff Acne Disability Index
      (CADI) scales from baseline to study end (eight weeks). All treatment emergent
      dermatological adverse events were evaluated for safety assessment. RESULTS: Out
      of 84 randomized subjects (43-nadifloxacin arm) and (41-clindamycin) 42 in
      nadifloxacin group, 37 in clindamycin group completed the study. Reduction from
      baseline of total, inflammatory and non-inflammatory lesion counts were highly
      significant in both the groups (P<0.0001), but between group differences were not
      significant. Significant improvement in CADI and IGA scales were noted in both
      groups. Between-group comparison showed no significant differences. The safety
      and tolerability profile of both regimens were good and statistically comparable.
      CONCLUSIONS: Topical nadifloxacin, a new fluoroquinolone is effective, tolerable,
      and safe for mild o moderate facial acne. Its clinical effectiveness is
      comparable to clindamycin when used as add-on therapy to benzoyl peroxide.

PMID- 22144764
TI  - Development of a simple radiant heat induced experimental pain model for
      evaluation of analgesics in normal healthy human volunteers.
AB  - OBJECTIVE: Human experimental pain models help to understand the mechanism of the
      painful conditions and can also be adopted to test analgesic efficacy of drugs.
      In early phases, the clinical development of new analgesics is hindered due to
      the lack of reliable tests for the experimental pain models. In the present
      study, we have developed and validated a simple radiant heat pain model which can
      be used for future screening of various analgesic agents. MATERIALS AND METHODS:
      We have standardized the thermal pain model by recording pain threshold and pain
      tolerance time in seconds at three different intensities and levels in 24 healthy
      subjects. Reproducibility of the test procedure was evaluated by recording the
      pain parameters by two observers on three consecutive days. Validity of model was
      further tested by evaluating the analgesic effect of tramadol. RESULTS AND
      CONCLUSIONS: Use of radiant heat pain model with high intensity and short level
      was found to produce low variability with coefficient of variation less than 5%.
      Interobserver and interperiod reproducibility was very good as shown by Bland -
      Altman plot; with most of the values within +/- 2SD. Tramadol produced
      statistically significant increase in pain threshold time. The newly developed
      pain model produces a type of experimental pain which is responsive to analgesic
      effects of tramadol at clinically relevant doses.

PMID- 22144765
TI  - Racemic salbutamol and levosalbutamol in mild persistent asthma: A comparative
      study of efficacy and safety.
AB  - AIM: The effect of monotherapy with racemic salbutamol and levosalbutamol on
      symptoms, quality of life, and pulmonary function has been assessed and compared
      in mild persistent asthma. MATERIALS AND METHODS: A randomized, open, parallel
      clinical study was conducted on 60 patients of mild persistent asthma. After
      baseline assessments, salbutamol was prescribed to 30 patients and levosalbutamol
      to another 30 for 4 weeks. The efficacy variables were change in asthma symptom
      scoring, pulmonary function test, and Mini Asthma Quality of Life Questionnaire
      (MiniAQLQ) scoring. At follow-up, the patients were re-evaluated and analyzed by
      statistical tools. RESULTS: Shortness of breath (P<0.001), chest tightness
      (P=0.033), wheeze (P=0.01), cough (P=0.024), and overall asthma symptom score
      (P<0.001) were significantly decreased in the levosalbutamol group in comparison
      to the salbutamol group. Results of MiniAQLQ revealed that improvement in
      symptoms (P=0.018), activity limitations (P=0.03), environmental stimuli
      (P=0.013)-related scoring and overall MiniAQLQ scoring (P<0.001) was
      statistically significant in the levosalbutamol group. Percentage reversibility
      of forced expiratory volume at one second (P=0.034), forced vital capacity
      (P=0.029), peak expiratory flow rate (P=0.0003) was found to be superior in the
      levosalbutamol group. CONCLUSION: Levosalbutamol was found to be superior
      compared to recemic salbutamol in mild persistent asthma.

PMID- 22144766
TI  - Antihyperlipidemic potential of Cedrus deodara extracts in monosodium glutamate
      induced obesity in neonatal rats.
AB  - OBJECTIVE: To study the antihyperlipidemic effect of Cedrus deodara (C. deodara)
      against monosodium glutamate (MSG) induced obesity in neonatal rats. MATERIALS
      AND METHODS: The studies were carried out on newborn neonatal rats and were
      injected intraperitoneally with 2 mg/g of MSG on the 2(nd) and 4(th) postnatal
      days and 4 mg/g on 6(th), 8(th) and 10(th) postnatal days. Ethanolic extract (EE)
      and acetone extract (AE) of C. deodara was administered in a dose of 100 and 200
      mg/kg, p.o./day at the age of 65 days. On day 60 of treatment, body weight,
      locomotor activity, body temperature, and various biochemical parameters like
      serum glucose, total cholesterol, triglyceride, and organs weights were recorded.
      RESULTS: There was a significant reduction in body weight, organs and increased
      body temperature, locomotor activity after treatment with extracts. C. deodara
      decreased serum glucose, total cholesterol and triglyceride, low density
      lipoprotein (LDL) and very low density lipoprotein (VLDL) levels and increased
      high density lipoprotein (HDL) significantly has compared to MSG-control rats.
      CONCLUSION: C. deodara extracts exhibited antihyperlipidemic effect and it
      possesses anti-obesity properties in MSG induced obese rats.

PMID- 22144767
TI  - Repeated administration of propofol upregulated the expression of c-Fos and
      cleaved-caspase-3 proteins in the developing mouse brain.
AB  - OBJECTIVES AND AIM: This study was designed to analyze the relationship between
      the expression of c-Fos protein and apoptosis in the hippocampus following
      propofol administration in infant mice. There are reports that certain drugs,
      including the general anesthetics applied in pediatrics and obstetrics, could
      block N-methyl-D-aspartate glutamate receptors and activate gamma-aminobutyric
      acid type A receptors. Furthermore, some anesthetics could trigger neuroapoptosis
      and the expression of c-Fos in the developing rodent brain. Propofol is a general
      anesthetic increasingly used in pediatrics and obstetrics, and is reported to be
      able to interact with both gamma-aminobutyric acid type A and N-methyl-D
      aspartate glutamate receptors. No adequate evaluations have been available as to
      whether the dosage of propofol to maintain anaesthesia could trigger the
      expression of c-Fos and apoptosis. MATERIALS AND METHODS: Intraperitoneal
      injections of propofol (50, 100 and 150 mg/kg) or vehicle were administered every
      90 minutes (4 times) in infant mice (5-7 days old). 30 minutes after the final
      administration, the protein expressions of c-Fos and cleaved-caspase-3 in the
      hippocampus were determined by immunohistochemistry and Western blotting.
      RESULTS: It was demonstrated that the expressions of cleaved-caspase-3 and c-Fos
      were upregulated in the hippocampal CA3 region in this study. CONCLUSIONS: The
      upregulated c-Fos expression induced by repeated injections of propofol might
      evoke neuroapoptosis.

PMID- 22144768
TI  - Protective effect of lisinopril on hepatic ischemia/reperfusion injury in rats.
AB  - OBJECTIVE: Ischemia/reperfusion (I/R) injury plays a key role in the pathogenesis
      of hepatic failure in several clinical settings such as liver resection or
      transplantation. Lisinopril, a widely prescribed drug for various cardiovascular
      conditions, has been reported to have diverse pharmacological properties. The aim
      of this study, therefore, was to evaluate a potential protective effect of
      lisinopril on hepatic I/R injury in rats. MATERIALS AND METHODS: In anesthetized
      rats, partial hepatic ischemia was applied for one hour followed by two hours
      reperfusion. Biochemical analysis of serum and hepatic tissue was done. Hepatic
      tissue was also subjected to electron microscopy. RESULTS: Pre-ischemic treatment
      with lisinopril (10 mg/kg) exerted protection against I/R-induced hepatocellular
      injury as evident by significant decrease in serum alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), and total bilirubin levels, along with
      hepatic lipid peroxidation, expressed as malondialdehyde content, with a
      concurrent increase in hepatic nitric oxide content as compared to I/R group. The
      electron microscopic examination indicated that lisinopril can effectively
      protect against hepatic I/R injury. CONCLUSION: Lisinopril provides a protection
      against hepatic I/R injury in rats. The protective effect is associated with
      reduction of oxidative stress-induced lipid peroxidation level and enhancement of
      nitric oxide availability.

PMID- 22144769
TI  - Protective effect of aqueous extract of Oroxylum indicum Linn. (root bark)
      against DNBS-induced colitis in rats.
AB  - OBJECTIVE: Aqueous root extract of Oroxylum indicum was evaluated in rats against
      dinitrobenzene sulfonic acid (DNBS) induced colitis. MATERIALS AND METHODS: Rats
      were pre-treated orally for seven days and continued for four days after the
      induction of colitis with OI(aq) (100, 200, and 400 mg/kg) or vehicle. Colitis
      was induced by intracolonic instillation of 25 mg of DNBS per rat dissolved in
      50% alcohol and 4 days later, the colonic mucosal damage was analyzed along with
      food intake, body weight, colon weight, spleen weight, histological damage,
      myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, reduced glutathione
      (GSH), and nitric oxide levels in colonic tissue homogenate. RESULTS: Significant
      reduction in gross damage area, weight loss and increase in colonic and spleen
      weight were evident in test substance-pretreated animals' dose dependently as
      compared to vehicle treated control. These effects were confirmed biochemically
      by a reduction in colonic myeloperoxidase activity, malondialdehyde levels,
      nitric oxide levels, and increase in reduced glutathione (GSH) levels.
      Furthermore, microscopic examination revealed diminution of inflammatory cell
      infiltration and submucosal edema in colon segments of rats treated with OI(aq).
      CONCLUSION: The results demonstrate the protective effect of OI(aq) in the animal
      model of acute colitis possibly through an antioxidant, anti-lipoperoxidative or
      due to reduction in nitric oxide generation.

PMID- 22144770
TI  - Screening of Ficus religiosa leaves fractions for analgesic and anti-inflammatory
      activities.
AB  - OBJECTIVE: To evaluate the different fractions of dried leaves of Ficus religiosa
      Linn for analgesic and anti-inflammatory activity using different models of pain
      and inflammation MATERIALS AND METHODS: The analgesic activity of F. religiosa
      carried out using acetic acid-induced writhing in mice and tail flick test in
      rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat
      paw edema and cotton pellet-granuloma formation in rats. Five different fractions
      (FRI, FRII, FRIII, FRIV and FRV) of F. religiosa at the dose level of 20 and 40
      mg/kg, p.o were tested. RESULTS: The fraction FRI (40 mg/kg, p.o.) and FRIII (40
      mg/kg, p.o) were found to be more effective (P<0.01) in preventing carrageenan
      induced rat paw edema, cotton pellet granuloma formation, and acetic acid induced
      writhing compared to the other fractions. FRI (20 mg/kg, p.o.) and FRIII (20
      mg/kg, p.o.) were also found to be more effective in increasing latency period in
      tail flick method. CONCLUSION: Out of five different fractions of F. religiosa
      leaves tested, FRI and FRIII possess potent analgesic and anti-inflammatory
      activities against different models of inflammation and pain.

PMID- 22144771
TI  - In vitro prevention of cataract by Oyster Mushroom Pleurotus florida extract on
      isolated goat eye lens.
AB  - OBJECTIVES: The aim of the present work was to evaluate the in vitro effect of
      Pleurotus florida extract cataract induced by glucose. MATERIALS AND METHODS:
      Goat eye lenses were divided into four groups. Group I lenses were incubated in
      artificial aqueous humor with glucose concentration 5.5 mM (normal control).
      Group II lenses were incubated with glucose concentration 55 mM (toxic control).
      Group III and IV lenses incubated with glucose concentration 55 mM were incubated
      along with hydroethanolic extract of P. florida 250 MUg/ml and 500 MUg/ml and
      subjected to morphological and biochemical evaluation. RESULTS: Group II lenses
      showed high amount of malondialdehyde (MDA) soluble and insoluble protein and
      decreased catalase and glutathione levels, while lenses treated with P. florida
      extract showed significant (P < 0.05) reduction in MDA, increased level of
      catalase (P < 0.001), glutathione (P < 0.005) and total and soluble protein.
      CONCLUSIONS: Hydroethanolic extract of P. florida showed prevention of in vitro
      glucose induced cataract. Thus, the goat lens model could be used for testing of
      various anticataract agents.

PMID- 22144772
TI  - Hepatoprotection through regulation of voltage dependent anion channel expression
      by Amomum subulatum Roxb seeds extract.
AB  - BACKGROUND AND PURPOSE: Voltage dependent anion channel (VDAC) plays an important
      role in triggering the opening of the mitochondrial permeability transition pore
      (PTP) that leads to mitochondrial damage and induce apoptic or necrotic cell
      death. In the present study, the methanolic extract of Amomum subulatum Roxb.
      seeds (MEAS) was used to examine its effect on VDAC. Aminotransferase activity,
      mitochondrial membrane potential, calcium-induced liver MPT, and VDAC expression
      were used to evaluate the hepato protective effect of MEAS. RESULTS: Pretreatment
      of mice with MEAS (100 and 300 mg/kg) significantly blocked the CCl(4)-induced
      increase in AST and ALT activities. Pretreatment with MEAS showed significant
      preservation of mitochondrial membrane potential as compared to CCl(4) control
      demonstrating the mitochondrial protection. In addition, pretreatment with MEAS
      at various concentrations exerted a dose-dependent effect against sensitivity to
      mitochondrial swelling induced by calcium. In addition, MEAS (300 mg/kg)
      significantly increased the transcription and translation of VDAC. CONCLUSION:
      Our data suggest that MEAS significantly prevents the damage to liver
      mitochondria through regulation of VDAC expression.

PMID- 22144773
TI  - Neuroprotective activity of Wedelia calendulacea on cerebral ischemia/reperfusion
      induced oxidative stress in rats.
AB  - OBJECTIVE: This study was undertaken to evaluate the neuroprotective activity of
      Wedelia calendulacea against cerebral ischemia/reperfusion induced oxidative
      stress in the rats. MATERIALS AND METHODS: The global cerebral ischemia was
      induced in male albino Wistar rats by occluding the bilateral carotid arteries
      for 30 min followed by 1 h and 4 h reperfusion. At various times of reperfusion,
      the histopathological changes and the levels of malondialdehyde (MDA),
      glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s
      transferase (GST), and hydrogen peroxide (H(2)O(2)) activity and brain water
      content were measured. RESULTS: The ischemic changes were preceded by increase in
      concentration of MDA, hydrogen peroxide and followed by decreased GPx, GR, and
      GST activity. Treatment with W. calendulacea significantly attenuated ischemia
      induced oxidative stress. W. calendulacea administration markedly reversed and
      restored to near normal level in the groups pre-treated with methanolic extract
      (250 and 500 mg/kg, given orally in single and double dose/day for 10 days) in
      dose-dependent way. Similarly, W. calendulacea reversed the brain water content
      in the ischemia reperfusion animals. The neurodegenaration also conformed by the
      histopathological changes in the cerebral-ischemic animals. CONCLUSION: The
      findings from the present investigation reveal that W. calendulacea protects
      neurons from global cerebral-ischemic injury in rat by attenuating oxidative
      stress.

PMID- 22144774
TI  - Kaurenic acid: Evaluation of the in vivo and in vitro antitumor activity on
      murine melanoma.
AB  - OBJECTIVE: The in vivo and in vitro antitumor activity of kaurenic acid [kaur 16
      en-19 oic acid] (KA) in melanoma was evaluated in a murine model in comparison
      with taxol (Tx). MATERIALS AND METHODS: B16F1 melanoma was developed in C57BL/6
      mice and cell cultures. Survival test, tumor growth, dissected-tumor
      measurements, histology, cytoxicity assay on cultured cells, and changes of
      apoptotic gene expression at mRNA level were analyzed. RESULTS: KA showed
      antitumor effect in vivo and in vitro and compared with Tx, its antimelanoma
      activity was greater (P < 0.001). These results were confirmed by morphological
      analysis (P < 0.001). In melanoma cell cultures, KA IC(50) was 0.79 MUM vs. 18.94
      MUM for Tx (P < 0.001). RT-PCR analysis demonstrated that Bcl-xL mRNA expression
      was altered in B16F1 mouse melanoma cells obtained from mice treated with either
      KA or Tx. CONCLUSION: The data suggest that KA is active in animal melanoma
      models, both in vitro and in vivo, being its cytotoxic effects stronger than
      those exhibited by Tx. Further trials should be conducted to elucidate its
      mechanism of action in melanoma with respect to necrosis or apoptotic processes.
      Our results support other evidences indicating that KA is a potential
      chemotherapeutic agent against cancer that has to be widely explored.

PMID- 22144775
TI  - Antidiarrheal potential of standardized extract of Rhododendron arboreum Smith
      flowers in experimental animals.
AB  - OBJECTIVE: To investigate standardized ethyl acetate fraction of Rhododendron
      arboreum (EFRA) flowers for antidiarrheal activity in experimental animals.
      MATERIALS AND METHODS: A simple sensitive high performance thin layer
      chromatography (HPTLC) method was used for the determination of hyperin in EFRA.
      The standardized fraction was investigated for castor oil, magnesium sulfate
      induced diarrhea, measurement of gastrointestinal transit using charcoal and
      castor oil-induced enteropooling. RESULTS: The concentration of hyperin in
      flowers of R. arboreum was found to be 0.148% by HPTLC. Oral administration of
      EFRA at 100, 200 and 400 mg/kg exhibited dose-dependent and significant (P<0.05
      0.001) antidiarrheal potential in castor oil and magnesium sulfate-induced
      diarrhea. EFRA at doses of 100, 200 and 400 mg/kg also produced significant
      (P<0.05-0.001) dose-dependent reduction in propulsive movement in castor oil
      induced gastrointestinal transit using charcoal meal in rats. EFRA was found to
      possess an antienteropooling in castor oil-induced experimental animals by
      reducing both weight and volume of intestinal content significantly. CONCLUSION:
      These findings demonstrate that standardized ethyl acetate fraction of R.
      arboreum flowers has potent antidiarrheal activity thus justifying its
      traditional use in diarrhea and have great potential as a source for natural
      health products.

PMID- 22144776
TI  - Chemical composition and vasorelaxant effect induced by the essential oil of
      Lippia alba (Mill.) N.E. Brown. (Verbenaceae) in rat mesenteric artery.
AB  - OBJECTIVES: To investigate the chemical composition and vasorelaxant effect of
      the essential oil of Lippia alba (EOLA) in rat mesenteric artery. MATERIAL AND
      METHODS: Chemical composition of EOLA was investigated by gas chromatography-mass
      spectrometry (GC/MS). Vasorelaxant effect was evaluated in vitro in rat superior
      mesenteric artery rings. RESULTS: GC/MS analysis revealed the presence of 19
      compounds, with geranial (48.58%) and neral (35.42%) being the major
      constituents. In intact rings precontracted with phenylephrine (Phe: 1 MUM), EOLA
      (100-1000 MUg/mL) induced relaxation, where the maximal effect (Emax) was 110.8
      +/- 10.8%. This effect was not modified after endothelium removal (Emax = 134.8
      +/- 16.5%), after tetraethylammonium (TEA) (Emax = 117.2 +/- 4.96%), or in rings
      precontracted with KCl (80 mM) (Emax = 112.6 +/- 6.70%). In addition, EOLA was
      able to inhibit the contraction caused by CaCl(2) and produced a small but
      significant (P<0.05) additional effect (from 70.5 +/- 3.4 to 105.3 +/- 13.5%, n =
      5) on the maximal relaxation of nifedipine (NIF: 10 MUM). CONCLUSIONS: The
      results demonstrated that EOLA induces endothelium-independent vasorelaxation,
      which appears to be caused, at least in part, by blocking Ca(2+) influx through
      voltage-operated Ca(2+) channels.

PMID- 22144777
TI  - Sedative and antiepileptic effects of Anthocephalus cadamba Roxb. in mice and
      rats.
AB  - OBJECTIVE: The aim of the present study was to evaluate the sedative and
      antiepileptic activities of ethanolic extract of Anthocephalus cadamba (ACE) bark
      in various experimental animal models. MATERIALS AND METHODS: ACE was tested at
      three doses viz. 100, 200 and 400 mg/kg p.o. We used ketamine-induced sleeping
      time model to test the sedative property of the extract where, onset and duration
      of sleep were observed. A paradigm of anticonvulsant models (pentylenetetrazole,
      isoniazid and maximal electroshock-induced seizures) were used to evaluate its
      protective effect against absence and generalized types of seizures. Onset of
      clonic convulsions, tonic extension and time of death were observed in PTZ and
      INH-induced seizure models. In MES model, duration of tonic hind leg extension
      and onset of stupor were observed. RESULTS: ACE showed significant increase in
      ketamine induced sleeping time. It also exhibited significant increase (P<0.05,
      0.01 and 0.001) in latency to clonic convulsion, tonic extension and time of
      death in PTZ and INH models at all tested doses, whereas in the MES model, the
      lower dose was found to be effective when compared with the higher doses (200 and
      400 mg/kg, p.o.). CONCLUSION: The results of the present investigation
      demonstrated that ACE possesses sedative and antiepileptic activities.

PMID- 22144778
TI  - A comparative study of dalteparin and unfractionated heparin in patients with
      unstable angina pectoris.
AB  - OBJECTIVE: To compare the efficacy and safety profile of dalteparin, a low
      molecular-weight heparin with a standard unfractionated heparin in patients with
      unstable angina pectoris. MATERIALS AND METHODS: This was a 6-month, prospective,
      parallel, randomized and open-labeled study. Patients of angina pectoris were
      randomized to receive either unfractionated heparin or dalteparin for 5 days.
      They were followed for 21 days during three visits on 1(st), 5(th) and 21(st)
      days. A series of resting electrocardiogram were undertaken in all patients on
      each visit. RESULTS: The frequency of the combined clinical outcome of death,
      myocardial infarction and recurrence of angina was similar during 21 days of
      follow-up with either dalteparin or intravenous unfractionated heparin. In
      patients who received dalteparin 2.43% patients developed minor bleeding in the
      form of epistaxis and 2.5% patients who received unfractionated heparin developed
      minor bleeding in the form of macroscopic hematuria. CONCLUSION: Dalteparin is as
      effective and safe as unfractionated heparin in the treatment of unstable angina.
      Dalteparin does not require routine laboratory monitoring as with unfractionated
      heparin.

PMID- 22144779
TI  - Subchronic treatment with fluoxetine attenuates the proerectile effect of
      Aspidosperma ulei Markgr (Apocyanaceae).
AB  - OBJECTIVE: To evaluate the ability of acute or chronic treatment with fluoxetine
      to alter the proerectile effect of Aspidosperma ulei alkaloid-rich fraction (F3
      5). MATERIALS AND METHODS: In the first series of experiments, three groups of
      mice received either a single intraperitoneal injection of vehicle, F3-5 (25
      mg/kg) or fluoxetine (10 mg/kg) + F3-5. Three behavioral responses were counted
      over a period of 30 min: erection, erection-like response and genital grooming.
      In a second series of experiments, animals treated for 13 days with fluoxetine or
      fluoxetine + F3-5 were assessed. RESULTS: A. ulei has been suggested to have
      proerectile effect in mice. Subchronic (13-d) treatment with fluoxetine resulted
      in a reduction in the number erections in F3-5-treated mice. CONCLUSION: Sexual
      dysfunction associated with antidepressant treatment continues to be a major
      compliance issue for antidepressant therapy. Acute administration of fluoxetine
      resulted in a near total reversal of the proerectile effect of F3-5.

PMID- 22144780
TI  - Anticonvulsant and muscle relaxant activity of the ethanolic extract of stems of
      Dendrophthoe falcata (Linn. F.) in mice.
AB  - OBJECTIVE: To investigate the anticonvulsant and muscle relxant activity of
      ethanolic extract of stems of Dendrophthoe falcata in mice. MATERIALS AND
      METHODS: The ethanolic extract of stems of D. falcata (100, 300 and 500 mg/kg,
      p.o.) was studied for its anticonvulsant effect on maximal electroshock-induced
      seizures and muscle relaxant activity at the same dose level using rota rod and
      traction test in mice. RESULTS: Preliminary phytochemical analysis revealed
      presence of proteins, carbohydrates, glycosides, steroids, triterpenes,
      flavonoids, tannins and phenolic compounds. D. falcata ethanolic extract (DFEE)
      (100, 300 and 500 mg/kg, p.o.) significantly (P<0.001) inhibited seizures induced
      by MES, reduced the duration of Hind limb tonic extensor phase (HLTE) and a
      decline in motor coordination. CONCLUSION: The ethanolic extract possesses
      anticonvulsant activity and muscle relaxant activity.

PMID- 22144781
TI  - Natriuretic and saluretic effects of Hemidesmus indicus R. Br. root extracts in
      rats.
AB  - OBJECTIVE: The present study was aimed to investigate the diuretic effects of
      aqueous (AqE) and ethanolic (EtE) crude extracts of Hemidesmus indicus R. Br.
      roots (family - Asclepiadaceae) using acute model in rats. MATERIALS AND METHODS:
      A single individual dose of AqE and EtE of H. indicus root (200 mg/kg and 400
      mg/kg, p.o., each), frusemide and hydrochlorothiazide, (25 mg/kg, p.o., each) as
      reference diuretic drugs were administered orally to dehydrated rats. Control
      group rats were fed with normal saline (25 ml/kg, p.o.). All rats were caged in
      metabolic cages in a pairs and their urine output was monitored at 5 and 24 h
      intervals. RESULTS: Both extracts significantly increased the urine output in
      higher doses. Although, the onset of this diuretic action was gradual (within 5
      h), it lasted throughout the studied period (up to 24 h). Further, the intensity
      of diuresis induced by AqE (400 mg/kg) in 5 h was almost similar to that of
      frusemide and hydrochlothiazide. AqE of H. indicus root also caused marked
      increase in urinary Na(+) and K(+) levels. However, the routine urinalysis showed
      non-significant alterations in pH and specific gravity by either dose of crude
      extracts of H. indicus roots. CONCLUSIONS: These effects demonstrate possible
      diuretic actions of H. indicus root extracts and support its folklore use in
      various urinary ailments. Further study need to be done to characterize active
      phytoconstituents.

PMID- 22144782
TI  - Aqueous extract of Annona squamosa (L.) ameliorates renal failure induced by 5/6
      nephrectomy in rat.
AB  - OBJECTIVE: To assess the renoprotective activity of the water extract of Annona
      squamosa in 5/6 nephrectomized animals. MATERIALS AND METHODS: For evaluating the
      renoprotective effects of Annona squamosa, 5/6 nephrectomized rats were used as a
      model for renal failure. The effects of hot-water extract of leaves of Annona
      squamosa L. (A. squamosa) at a dose 300 mg/kg bw on biochemical and urinary
      parameters like plasma urea, plasma creatinine, and urine creatinine were
      analyzed. For elucidating its effect on oxidative stress, renal superoxide
      dismutase (SOD) levels were measured. RESULTS: Nephrectomized rats (5/6) showed a
      significant rise in plasma urea and creatinine levels with a stable fall in urine
      creatinine. Treatment with A. squamosa extract (300 mg/kg bw) lead to a
      significant fall in the plasma urea and creatinine values with partial
      restoration to normal values along with a significant rise in the activity of
      SOD. CONCLUSION: Thus, therapeutic strategies against oxidative stress could be
      effective in renal diseases. This study provides an indication to investigate
      further the efficacy of A. squamosa as a novel agent for alleviating renal
      failure.

PMID- 22144783
TI  - Role of hemodialysis in baclofen overdose with normal renal function.
AB  - The treatment of baclofen overdose is primarily supportive. There have been case
      reports of hemodialysis being used in patients with chronic kidney disease with
      baclofen overdose. A case report of hemodialysis in a baclofen-overdose patient
      with normal renal function is presented. Review of literature has also been
      provided.

PMID- 22144784
TI  - Treatment of early arthritis using arthrofoon (ultra-low doses of antibodies to
      tumor necrosis factor-alpha).
AB  - The main aim of treatment of early rheumatoid arthritis (RA) should be to achieve
      clinical remission to prevent structural damage and physical disability.
      Arthrofoon modifies production/activity of endogenous inhibitors of tumor
      necrosis factor-alpha (TNF-alpha). The sublingual rout is the most acceptable to
      ambulatory treatment because it does not produce the adverse reactions associated
      with intravenous therapy. The treatment with arthrofoon in outpatient with early
      RA is analyzed here. This report is devoted to the 28-year-old Russian woman who
      received arthrofoon due to suspicion of early RA. The strategy of early
      prescription of ultra-low doses of TNF-alpha antibody within two years was
      confirmed by the clinical improvement and delay of radiological disease
      progression in patient with undifferentiated arthritis or probable RA initially.

PMID- 22144785
TI  - Severe thrombocytopenia following tirofiban infusion.
AB  - A 44-year-old man presented with acute coronary syndrome. He was administered
      glycoprotein IIb/IIIa receptor antagonist (tirofiban) for a left anterior
      descending artery thrombus detected during percutaneous coronary intervention. He
      developed very severe thrombocytopenia 24 h after tirofiban infusion with no
      signs of bleeding. The thrombocytopenia spontaneously resolved after stopping
      tirofiban without any significant clinical sequelae. To our knowledge, this is
      the first case report of tirofiban-induced severe thrombocytopenia from the
      Middle East. Clinicians using this drug should be aware of this potentially
      lethal adverse drug reaction. Close monitoring of platelet count early after the
      initiation of tirofiban infusion is suggested and discontinuation of tirofiban
      infusion can reverse thrombocytopenia spontaneously.

PMID- 22144786
TI  - Zolpidem withdrawal delirium.
AB  - The Z-category hypnotics are promoted for their relative safety. However, this
      view is challenged by the emerging clinical evidence in the form of zolpidem
      related intoxication delirium and seizures, and dependence and complicated
      withdrawal. We report the case of a zolpidem-naive alcohol-dependent inpatient
      that, while undergoing alcohol de-addiction, was prescribed zolpidem for insomnia
      and developed delirium during taper-off. He was successfully detoxified for
      alcohol, treated for delirium and put on disulfiram prophylaxis. The case
      highlights the need for being cautious while using zolpidem for insomnia in
      alcohol dependent subjects.

PMID- 22144787
TI  - Phenytoin induced chorea in a pediatric patient: An interaction between
      phenytoin, phenobarbital and clobazam.
AB  - A 3-year-old female patient developed chorea possibly due to an interaction
      between phenytoin, phenobarbital and clobazam used for generalized tonic clonic
      seizures. Phenytoin withdrawal resulted in recovery within 24 hours. Post
      reaction computerized tomography (CT)-scan of brain was normal. Combined use of
      anti-seizure drugs and interactions between them may be responsible for the
      reaction. Therapeutic drug monitoring is important while prescribing two or more
      anti-seizure drugs.

PMID- 22144788
TI  - Azathioprine induced cholestatic hepatitis.
AB  - We report a case of cholestatic hepatitis developed one week after exposure to
      azathioprine. The subsequent prolonged cholestatic phase was followed by full
      clinical remission. Current knowledge on pathogenesis and epidemiology and the
      diagnostic challenges presented by this rare complication are discussed, followed
      by recommendations for monitoring and management.

PMID- 22144789
TI  - Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in
      asymptomatic dilated cardiomyopathy.
AB  - Azithromycin is a widely used macrolide derivative and has generally been
      considered to be a very safe medication. Though gastrointestinal symptoms and
      reversible hearing loss are common, potentially serious side effects including
      angioedema and cholestatic jaundice occurred in less than one percent of
      patients. We report a case of asymptomatic dilated cardiomyopathy with
      Azithromycin induced severe hepatocellular toxicity and hepatic encephalopathy.

PMID- 22144790
TI  - Nevirapine induced exfoliative dermatitis in an HIV-infected patient.

PMID- 22144791
TI  - Hyperprolactinemia and breast enlargement with serotonin reuptake inhibitor and
      olanzapine combination.

PMID- 22144792
TI  - Anti-inflammatory and in vitro antioxidant activity of Desmodium triquetrum (L.).

PMID- 22144793
TI  - Efficacy of amprolium and toltrazuril in chicken with subclinical infection of
      cecal coccidiosis.

PMID- 22144794
TI  - Anthelmintic effect of Euphorbia prostrata Ait. extracts.

PMID- 22144795
TI  - Tolerance of bladder antispasmodics in children with urinary incontinence: An
      observational study from North India.

PMID- 22144796
TI  - The truth behind numbers.

PMID- 22144797
TI  - Optimizing tooth form with direct posterior composite restorations.
AB  - Advances in material sciences and technology have provided today's clinicians the
      strategies to transform the mechanistic approach of operative dentistry into a
      biologic philosophy. In the last three decades, composite resins have gone from
      being just an esthetically pleasing way of restoring Class III and Class IV
      cavities to become the universal material for both anterior and posterior
      situations as they closely mimic the natural esthetics while restoring the form
      of the human dentition. In order to enhance their success, clinicians have to
      rethink their protocol instead of applying the same restorative concepts and
      principles practiced with metallic restorations. Paralleling the evolution of
      posterior composite resin materials, cavity designs, restorative techniques and
      armamentarium have also developed rapidly to successfully employ composite resins
      in Class II situations. Most of the earlier problems with posterior composites
      such as poor wear resistance, polymerization shrinkage, postoperative
      sensitivity, predictable bonding to dentin, etc., have been overcome to a major
      extent. However, the clinically relevant aspect of achieving tight contacts in
      Class II situations has challenged clinicians the most. This paper reviews the
      evolution of techniques and recent developments in achieving predictable contacts
      with posterior composites. A Medline search was performed for articles on "direct
      posterior composite contacts." The keywords used were "contacts and contours of
      posterior composites." The reference list of each article was manually checked
      for additional articles of relevance.

PMID- 22144798
TI  - Comparison of the push-out shear bond strength of four types of glass ionomers
      when used to bond amalgam: An in vitro study.
AB  - BACKGROUND: Dental amalgam is the primary direct posterior restorative material
      used worldwide, but it have certain shortcomings due to the lack of adhesiveness
      to the cavity. The introduction of the concept of bonded amalgam helped improve
      the use of amalgam as a restorative material. AIM: Evaluation of the comparative
      push-out shear bond strength of four types of conventional glass ionomers used to
      bond amalgam to tooth in simulated class I situations. MATERIALS AND METHODS:
      FOUR CHEMICAL CURE GLASS IONOMERS ARE USED: GC Fuji I, GC Fuji II, GC Fuji III
      and GC Fuji VII, and are compared with unbonded amalgam. The push-out bond
      strength was tested using the Instron Universal Testing Machine at a crosshead
      speed of 0.5 mm/min. STATISTICAL ANALYSIS: One-way ANOVA and post hoc Bonferroni
      tests were used to analyze the data. RESULTS: The results showed that the use of
      glass ionomer to bond amalgam resulted in an increase in the bond strength of
      amalgam. The Type VII glass ionomer showed the highest bond strength in
      comparison with the other glass ionomers. CONCLUSIONS: Conventional glass ionomer
      bonds to amalgam and shows a beneficial increase in the bond strength of the
      restoration in comparison with unbonded amalgam.

PMID- 22144799
TI  - Effect of fiber orientation and type of restorative material on fracture strength
      of the tooth.
AB  - AIM: To determine the effect of fiber and its orientation on the fracture
      resistance of composite restorations in root-filled premolars. MATERIALS AND
      METHODS: 50 sound human premolars were collected and assigned to five groups of
      ten specimens each. In group 1 (control), specimens were not root-filled. In the
      other four groups, MOD cavities were prepared and the cusps were reduced to 1.5
      mm. In groups 2 and 3, the samples were filled with Z-250 and spectrum composites
      respectively without fiber reinforcement. Groups 4 and 5 were reinforced with
      Fiber-Ribbon-(Angelus) and restored with spectrum composite. Fibers were placed
      in the U-shaped design in group 4 while they were placed in the cross-shape in
      occlusal region in group 5. The fracture resistance was tested using a mechanical
      testing machine at crosshead speed of 1mm/min. RESULTS: The fracture strength of
      control group was 1271.16+/-722.04 N while it was 952.05+/-330.16 N for group 2,
      918.52+/-256.6 N for group 3, 857.13+/-184.58 N for group 4 and 1138.81+/-406.64
      N for group 5. Fracture strength of group 5 was more than other groups except for
      group 1, there was no statistically significant differences. CONCLUSIONS: The
      reinforcement of composite with fiber does not increase fracture resistance of
      root-filled premolars significantly.

PMID- 22144800
TI  - Morphologic characteristics of root canal of mandibular incisors in North-East
      Indian population: An in vitro study.
AB  - AIM: To aim of this study is to investigate the root canal characteristics of
      mandibular incisors in a North East Indian population using a canal staining and
      tooth-clearing technique. MATERIALS AND METHODS: Four hundred and eighty
      extracted mandibular incisors, collected from dental clinics within North East
      India were selected for this study. Following pulp tissue removal, the teeth were
      decalcified with 5% nitric acid, dehydrated with ascending concentrations of
      alcohol and rendered clear by immersion in methyl salicylate. After staining of
      the canal systems with India ink, cleared teeth were examined under 5X
      magnification and the following features were evaluated: (i) number and type of
      root canals; (ii) presence and location of lateral canals and intercanal
      communications; (iii) location of apical foramina; and, (iv) Bifurcation of
      canals. RESULTS: The majority of mandibular incisors had a single canal (63.75%
      of teeth possessed a Type I canal system). Although 36.25% of the roots possessed
      two canals, only 6.25% had two separate apical foramina. CONCLUSIONS: The
      prevalence of two canals in this group (of North East Indians) of mandibular
      incisors was 36.25% and is within the range of previous studies performed on
      populations of different racial origin.

PMID- 22144801
TI  - A comparative study on dental pulp response to calcium hydroxide, white and grey
      mineral trioxide aggregate as pulp capping agents.
AB  - CONTEXT: Vital pulp therapy has been known as one of the treatment options to
      preserve pulp after being exposed by trauma or caries. AIM: To investigate human
      pulpal response to white and grey mineral trioxide aggregate (WMTA, GMTA) and
      Dycal (MTA) as pulp capping agents. SETTING AND DESIGN: Human volunteers were
      participated in this randomized clinical trial. MATERIALS AND METHODS: This study
      was conducted on 90 intact first and second premolars of human maxillary and
      mandibular teeth. The teeth were randomly assigned into three groups of 30 each.
      Under local anesthesia, teeth were exposed and capped either with GMTA, WMTA, or
      Dycal. After 30, 60, and 90 days 10 teeth of each group were extracted and
      prepared for histologic observation. STATISTICAL ANALYSIS: Histopathologic data
      were analyzed by chi(2), Kruskal Wallis and Mann Whitney tests. RESULTS: the
      calcified bridge in teeth that were capped with GMTA was significantly thicker
      than Dycal at 30 and 60 days (P= 0.015 and P=0.002, respectively); whereas WMTA
      showed significantly thicker calcified bridge than Dycal at 90 days (P=0.02). In
      addition, GMTA specimens showed significantly less inflammation compared to Dycal
      samples at 90 days interval (P=0.019). No significant difference was found
      between GMTA and WMTA in terms of calcified bridge thickness and pulp
      inflammatory response to the capping materials (P>0.05). CONCLUSIONS: Based on
      the result of this study, both types of MTA can be suggested as the materials of
      choice for direct pulp capping procedure instead of Dycal as hard setting calcium
      hydroxide cement.

PMID- 22144802
TI  - Evaluation of the effect of concentration and duration of application of sodium
      ascorbate hydrogel on the bond strength of composite resin to bleached enamel.
AB  - AIM: The effect of different concentrations of hydrogel of sodium ascorbate on
      bond strength of bleached enamel for varying periods of time and the mode of
      failure was evaluated. MATERIALS AND METHODS: Seventy enamel surfaces were
      obtained from 35 human extracted premolars. Specimens were divided into four
      groups: no bleaching (control), bleaching with carbamide peroxide gel, bleaching
      and application of 10% / 20% sodium ascorbate hydrogel for 30, 60, 120 min.
      Surfaces were bonded with a total etch bonding system and composite resin.
      Specimens were tested for shear bond strength. Mode of failure was determined by
      stereomicroscope. Data were analyzed using a two-way analysis of variance, and
      Scheffe's post hoc test. RESULTS: Sodium ascorbate hydrogel application following
      bleaching increased the resin-enamel bond strength and was directly proportional
      to its duration of application. However, there was no difference in bond strength
      with an increase in the concentration of sodium ascorbate hydrogel. CONCLUSION:
      Immediate bonding of composite resin to bleached enamel is possible after
      treatment with antioxidant sodium ascorbate hydrogel.

PMID- 22144804
TI  - Effect of various endodontic solutions on punch out strength of Resilon under
      cyclic loading.
AB  - BACKGROUND: Before obturation, various endodontic solutions are used as a final
      rinse. These solutions might affect the bond strength of Resilon-Epiphany system.
      The aim of this study was to evaluate the effect of NaOCl (5.25%), chlorhexidine
      CHX (2%), EDTA solution (17%), and BioPure MTAD on push out bond strength of
      Resilon-Epiphany system. MATERIALS AND METHODS: Seventy-five human premolar roots
      were prepared and divided on the basis of final endodontic solution rinse. The
      canals were obturated with Resilon-Epiphany system. All samples were restored
      using a fiber post system and indirect composite crown. The samples received 150
      000 cycles of mechanical loading. Push out bond strength was performed in the
      apical third of root having Resilon obturation. RESULTS AND CONCLUSIONS:
      Different endodontic solutions tested, did not affected the push out bond
      strength of Resilon-Epiphany obturation system.

PMID- 22144803
TI  - Effect of storage time on microtensile bond strength between quartz fiber post
      and composite core after different post surface treatments.
AB  - AIM: The aim was to evaluate the influence of water storage on fiber post-resin
      composite adhesion after different postsurface treatments. MATERIALS AND METHODS:
      Forty-two fiber posts were used. Half of them were treated by hydrogen-peroxide
      and the other half were sandblasted. The adhesive (Single Bond, 3M, USA) was
      applied on the post. Core was built-up using flowable composite (AElite Flow,
      Bisco, USA). The specimens were divided into eight groups. Group 1 was treated
      with H(2)O(2). Groups 2-4 were treated with H2O2 but stored for 3, 6, and 9
      months, respectively. Groups 5-8 were sandblasted and stored for 0, 3, 6, and 9
      months. MUTBS was measured and data analyzed using one-way ANOVA and Tukey HSD.
      The fractured surfaces were evaluated by a stereomicroscope. The morphology of
      interfaces was assessed under SEM. H(2)O(2)-treated groups showed higher bond
      strength. RESULTS: The effect of "surface-treatment method" and "storage-time"
      was significant (P<0.0001), but there was no significant difference for their
      interaction effect (P=0.05). Water aging significantly decreased MUTBS.
      CONCLUSIONS: Water aging significantly decreased microtensile bond strength
      regardless of the type of post surface treatment.

PMID- 22144805
TI  - Microhardness of dual-polymerized resin cement around a translucent fiber post in
      the intraradicular environment.
AB  - AIM: In this study, we evaluated the effect of photopolymerization on Vickers
      microhardness of dual-polymerized resin cement at three locations when a
      translucent quartz fiber post was used. MATERIALS AND METHODS: Single-rooted
      bovine teeth received quartz fiber post systems (length: 12 mm) using a dual
      polymerized resin cement. In Group 1, the posts were cemented but not
      photopolymerized, and in Group 2, the posts were both cemented and
      photopolymerized. After cementation, approximately 1.5-mm thick sections were
      obtained (two cervical, two middle, and two apical) for regional microhardness
      evaluations. STATISTICAL ANALYSIS: Statistical analyses were performed using the
      SPSS software (ver. 11.0 for Windows; SPSS, Inc., Chicago, IL, USA).
      Microhardness (kg/mm(2)) data were submitted to two-way analysis of variance (two
      way ANOVA) and repeated measures with microhardness values as the dependent
      variable and polymerization status (two levels: with and without) and root region
      (three levels: cervical, middle, and apical) as independent variables. Multiple
      comparisons were made using Dunnett's T3 post-hoc test. P values of <0.05 were
      considered to indicate statistical significance in all tests. RESULTS:
      Photopolymerization did not significantly change the microhardness values when
      compared with no photopolymerization. Microhardness values also showed no
      significant difference between the three regions in the root canals in both
      groups. CONCLUSIONS: The mode of polymerization of the cement tested in
      combination with the translucent quartz fiber post system did not affect the
      microhardness of the cement at the cervical, middle, or apical regions of the
      root.

PMID- 22144806
TI  - Effect of chlorhexidine cavity disinfection on microleakage in cavities restored
      with composite using a self-etching single bottle adhesive.
AB  - AIMS: This study evaluated the effect of 2% chlorhexidine cavity disinfectant on
      microleakage in class II cavities restored with light cured composites using a
      single bottle adhesive in an in vitro model. MATERIALS AND METHODS: Proximal box
      cavities were prepared on mesial and distal surfaces of 40 non carious mandibular
      third molars, resulting in total of 80 cavities. Forty cavities on were rinsed
      with normal saline and 40 cavities were rinsed with 2% chlorhexidine cavity
      disinfectant. All cavities were restored with a single bottle adhesive and nano
      hybrid composite resin. Microleakage was evaluated at the gingival margin using
      methylene blue dye penetration method. RESULTS AND CONCLUSION: Chlorhexidine
      cavity disinfectants produced significantly higher microleakage while restoring
      the cavities using a self-etching single bottle adhesive.

PMID- 22144807
TI  - A retrospective clinical evaluation of success rate in endodontic-treated
      premolars restored with composite resin and fiber reinforced composite posts.
AB  - BACKGROUND: The aim of this retrospective study was to assess the survival rate
      and causes of failure of quartz fiber posts used to restore endodontically
      treated teeth. MATERIALS AND METHODS: Thirty-eight patients with endodontically
      treated premolar and anterior teeth that were then restored with a
      coronoradicular quartz fiber post and extensive composite resin restorations were
      selected for participation in the study. The age of the restorations ranged from
      1 to 6 years. Survival probabilities of the restorations as well as causes of
      failures were analyzed using the Kaplan-Meier analysis and the Logistic
      regression (alpha = 0.05). RESULTS: The overall cumulative survival rate (48.8%)
      was determined, while the survival probabilities after 1, 2, 4, 5, and 6 years of
      service were 88.37%, 60.95%, 45.71%, 32.65%, and 0%, respectively. CONCLUSIONS:
      The survival probability of endodontically treated teeth restored with a quartz
      fiber post and composite restorations is associated with the dental arch.

PMID- 22144808
TI  - Contemporary curing profiles: Study of effectiveness of cure and polymerization
      shrinkage of composite resins: An in vitro study.
AB  - AIMS: This study was undertaken to determine the effect of step-curing, ramp
      curing, single intensity on the effectiveness of cure and polymerization
      shrinkage of composite resin. The influence of filler loading on the
      effectiveness of cure and polymerization shrinkage of composite resin was
      investigated. MATERIALS AND METHODS: In this study, a total of 80 specimens
      divided into four groups were used. Group I - specimens cured with the step-cure
      mode. Group II - specimens cured with single high intensity. Group III -
      specimens cured with the ramp-cure mode. Group IV - specimens cured with single
      low intensity. Each group had two subgroups based on the composite resins used
      for making the specimen. The effectiveness of cure was determined from surface
      hardness values obtained from Rockwell hardness testing. A mathematical
      volumetric method was used to assess the volumetric shrinkage. RESULTS: Group III
      showed the best effectiveness of cure followed by group I and II. Group IV showed
      the least. Polymerization shrinkage was highest with group III and group II, were
      as was lowest for group I and IV. Charisma showed better effectiveness of cure
      and low polymerization shrinkage compared to Durafill VS. CONCLUSION: This study
      emphasizes on the fact that, the soft-start polymerization modes (step curing and
      ramp curing) should be preferentially used over the conventional single (high or
      low light) intensities to cure composite resins, as its use results in optimal
      properties.

PMID- 22144809
TI  - Different surface preparation techniques of porcelain repaired with composite
      resin and fracture resistance.
AB  - BACKGROUND: Porcelain from prosthesis such as crown or bridge can be fractured if
      exposed to trauma; and, can be repaired at chairside using composite resin. AIM:
      To investigate the fracture resistance of few techniques of surface preparation
      in repairing fractured porcelain using composite resin. MATERIALS AND METHODS:
      Eighty samples of porcelain blocks were divided into 4 groups for different
      surface preparations, such as, Cimara repairing kit; porcelain etch kit
      containing hydrofluoric acid; Panavia F resin cement; and, sandblasting using
      aluminium oxide, before composite resin (Filtek Z250, 3M ESPE) was bonded to the
      prepared porcelain blocks. Twenty others samples in the control group comprised
      of pure porcelain blocks. The fracture resistance of each sample was tested using
      Instron machine (UK). RESULTS: With the exception of the group repaired using
      hydrofluoric acid (3.04+/-1.04 Mpa), all the other groups showed significant
      difference in the fracture resistance values when compared to the control group
      (3.05 +/- 1.42 MPa) at P<0.05. CONCLUSIONS: Etching of the porcelain blocks with
      hydrofluoric acid holds promise in the repair of fractured porcelain with
      composite resin at chairside.

PMID- 22144810
TI  - Spectrophotometric and colorimetric evaluation of staining of the light cured
      composite after exposure with different intensities of light curing units.
AB  - AIM/OBJECTIVE: To understand the importance of intensity of light in polymerizing
      light cured composites and its relation to color stability. MATERIALS AND
      METHODS: Forty specimens of composite disc with 3mm diameter and 1.5 mm thick
      were divided into two groups of 20 samples each. Group1: Twenty samples were
      cured with a light curing unit of380mw/cm(2). Group2: Twenty samples cured with a
      light curing unit of 680mw/cm(2). These polymerized samples were immersed in
      methylene blue dye for 24hoursand later washed and immersed in absolute alcohol
      for 24 hours. The amount of color released into absolute alcohol was assessed by
      spectrophotometric and colorimetric analysis. RESULTS: Results were analyzed for
      spectrophotometric and colorimetric values by using the Mann-Whitney test. The
      group cured with low intensity light stained more compared to the group cured
      with a normal intensity of light. CONCLUSIONS: Intensity of light plays a crucial
      role in staining of the polymerized light cured composite. The intensity of the
      curing unit has to be maintained in acceptable limits to achieve good clinical
      results.

PMID- 22144812
TI  - Ex vivo fracture resistance of endodontically treated maxillary central incisors
      restored with fiber-reinforced composite posts and experimental dentin posts.
AB  - AIM: To compare the fracture resistance of teeth restored with fiber-reinforced
      composite (FRC) posts and experimental dentin posts milled from human root
      dentin. MATERIALS AND METHODS: Thirty maxillary central incisors were divided
      into three groups of ten each. Twenty teeth were restored with FRC posts and
      solid dentin posts and numbered as Groups 2 and 3 respectively while Group 1
      acted as the control, without any post. The teeth were loaded at 135 degrees 
      angle to their long axes after core build-up and the failure loads were recorded.
      RESULTS: One-way Analysis of Variance (ANOVA) and Bonferroni multiple comparisons
      revealed a significant difference among test groups with the control group
      showing the highest fracture resistance, followed by the dentin post group and
      lastly the FRC post group. CONCLUSIONS: Teeth restored with dentin posts
      exhibited better fracture resistance than those restored with FRC posts.

PMID- 22144811
TI  - Caries-risk assessment with a chairside optical spectroscopic sensor by
      monitoring bacterial-mediated acidogenic-profile of saliva in children.
AB  - OBJECTIVE: This study aimed to evaluate the ability of an optical spectroscopic
      sensor (OSS) to monitor bacterial-mediated acidogenic-profile of saliva resulting
      from bacteria-sucrose interaction. MATERIALS AND METHODS: Stage-1,
      characterization experiments were conducted to standardize the OSS. Stage-2
      clinical experiments were carried out on stimulated saliva samples from 70
      children of age-group 1-12 years. The bacterial-mediated acidogenic-profile of
      saliva mixed with sucrose was monitored using the OSS for 180 minutes. RESULTS:
      The clinical patients were categorized based on the dmfs score as caries-active,
      caries-inactive and caries-free. The bacterial-mediated acidogenic-profile
      measured in terms of t1/2 monitored using the OSS was significantly different
      between the caries-free and caries-active (P<0.05); and caries-free and caries
      inactive groups (P<0.005). CONCLUSIONS: The significant correlation of the
      acidogenic-profile determined using the OSS and the caries-status highlighted the
      OSS as a sensitive and rapid chairside tool for the quantification of the
      acidogenic-profile of saliva that could help in monitoring the caries-risk in
      children.

PMID- 22144813
TI  - Cytotoxicity evaluation of a new fast set highly viscous conventional glass
      ionomer cement with L929 fibroblast cell line.
AB  - AIM: This study aims to evaluate the cytotoxicity of a new fast set highly
      viscous conventional glass ionomer cement (GIC) with L929 fibroblasts. MATERIALS
      AND METHODS: The cement capsule was mixed and introduced into a paraffin wax
      mould. After setting, the cement was incubated in Dulbecco's Modified Eagle's
      Medium. Six replicates of the material extract were added to the culture medium
      in 96-well plates. L929 mouse fibroblast cells were added into the wells and then
      incubated for 48 h. Dimethylthiazol diphenyltetrazolium bromide test was
      performed for cytotoxicity evaluation. RESULTS: The results showed that this GIC
      brand did not yield a half-maximal inhibitory concentration value, IC50, as the
      cell viability was above 50% at all concentrations. Cell viability over 90% was
      observed at the concentrations of 3.125 and 1.5625 mg/ml. Maximum concentration
      of the material showed cell viability of 59.4%. CONCLUSIONS: This new fast set
      highly viscous conventional GIC showed low cytotoxicity to mouse fibroblast
      cells, and it can be suggested as a substitute for dental cements exhibiting a
      long setting time.

PMID- 22144814
TI  - Clinical evaluation of giomer- and resin-modified glass ionomer cement in class V
      noncarious cervical lesions: An in vivo study.
AB  - OBJECTIVES: To evaluate and compare the clinical performance of Giomer (Beautifil
      II) and RMGIC (Fuji II LC) in noncarious cervical lesions. MATERIALS AND METHODS:
      Thirty-two subjects with one or two pairs of noncarious cervical lesions were
      included in the study. Each pair of lesion was restored with either giomer or
      RMGIC assigned randomly. Clinical evaluation of restorations was done using USPHS
      criteria. Data was formulated in a predesigned format and subjected to
      statistical analysis using the chi square test. RESULTS: Statistically
      significant difference was found between RMGIC and Giomer with respect to surface
      roughness with P value <0.001. CONCLUSION: Giomer showed superior surface finish
      compared to RMGIC. Both Giomer and RMGIC showed equal retention ability.

PMID- 22144815
TI  - In vitro evaluation of microleakage of class II packable composite resin
      restorations using flowable composite and resin modified glass ionomers as
      intermediate layers.
AB  - AIM AND OBJECTIVES: To evaluate the cervical marginal microleakage of class II
      packable composite resin restorations using flowable composite and resin modified
      glass ionomer as intermediate layers and whether the difference in the thickness
      of these intermediate layers would influence the microleakage. MATERIALS AND
      METHODS: Standardized class II box only cavities (4 mm bucco lingual width 2 mm
      mesio distal depth with the gingival margin 1 mm above the cemento-enamel
      junction (CEJ) were restored as follows: Group A Restoration with packable
      composite alone, Group B, Subgroup 1, 1 mm flowable composite liner + packable
      composite, Sub Group 2, 2 mm flowable composite liner + packable composite, Group
      C, Subgroup 1, 1 mm resin modified glass ionomer cement (RMGIC) liner + packable
      composite, Sub Group 2, 2 mm RMGIC liner + packable composite, The specimens were
      thermocycled, stained with methylene blue, sectioned to evaluate the dye
      penetration. Data were analyzed using Kruskall Wallis Test and Mann Whitney U
      test. RESULTS: There was no statistically significant difference between the
      groups. The difference in the thickness of the intermediate layers did not
      influence the microleakage. CONCLUSIONS: Use of 1 mm of flowable composite
      intermediate layer improved the sealing ability of packable composites than the
      differential thickness of resin modified glass ionomer.

PMID- 22144816
TI  - Light induced fluorescence evaluation: A novel concept for caries diagnosis and
      excavation.
AB  - In the era of minimal invasive dentistry, every effort should be directed to
      preserve the maximum tooth structure during cavity preparation. However, while
      making cavities, clinicians usually get indecisive at what point caries
      excavation should be stopped, so as to involve only the infected dentin. Apparent
      lack of valid clinical markers, difficulties with the use of caries detector dyes
      and chemo mechanical caries removal systems carve out a need for an improved
      system, which would be helpful to differentiate between the healthy and infected
      dentin during caries excavation. Light induced fluorescence evaluation is a novel
      concept implicated for caries detection and for making decisions while cavity
      preparation. This paper describes a few cases that explain the clinical
      applicability of this concept, using the SoproLife camera that works on this
      principle. Autofluorescence masking effect was found to be helpful for caries
      detection and the red fluorescence in the treatment mode was found helpful in
      deciding 'when to stop the excavation process.' Light induced fluorescence
      evaluation - Diagnosis - Treatment concept concept can be used as a guide for
      caries detection and excavation. It also facilitates decision making for stopping
      the caries excavation so as to involve infected dentin only.

PMID- 22144817
TI  - Novel treatment of white spot lesions: A report of two cases.
AB  - This case report describes a technique used to treat smooth surface white spot
      lesions microinvasively. It is based on the infiltration of an initial enamel
      caries lesion with low-viscosity light-curing resins called infiltrants. The
      surface layer is eroded and desiccated, followed by resin infiltrant application.
      The resin penetrates into the lesion microporosities driven by capillary force
      and is hardened by light curing. Infiltrated lesions lose their whitish
      appearance and look similar to sound enamel. Additionally, the treatment prevents
      lesion progression. This technique might be an alternative to microabrasion and
      restorative treatment in treating of white spot lesions of esthetically relevant
      teeth.

PMID- 22144818
TI  - Calcium-enriched mixture cement as artificial apical barrier: A case series.
AB  - In comparison to the conventional apexification using calcium hydroxide,
      artificial apical barrier technique is more valuable and less time consuming.
      This article describes successful use of calcium-enriched mixture (CEM) cement as
      an artificial apical barrier in open apices. In this study, 13 single-rooted
      teeth with necrotic pulps and open apices were treated non-surgically. After
      copious irrigation of the root canals with NaOCl 5.25% and gentle filing, based
      on need for interappointment dressing, treatments were followed by CEM cement
      (BioniqueDent, Tehran, Iran) apical plug insertion in the first or second
      appointment. All cases were then permanently restored. All subjects were followed
      until radiographic evidence of periradicular healing was seen (mean 14.5 months).
      Clinically, all cases were functional and asymptomatic and complete osseous
      healing was observed in all the teeth. Considering the biological properties of
      CEM cement, this new endodontic biomaterial might be appropriate to be used as
      artificial apical barrier in the open apex teeth.

PMID- 22144820
TI  - Maxillary first Molar with three canal orifices in MesioBuccal root.
AB  - The present case describes root canal treatment in a maxillary first molar with
      unusual anatomy. A male patient was referred for the treatment of maxillary left
      first molar tooth. Clinical examination of the pulpal floor revealed 3 orifices
      in the mesio buccal root. The tooth was treated successfully. Anatomic variations
      must be taken into consideration in clinical and radiographic evaluation during
      endodontic treatment.

PMID- 22144819
TI  - Anterior fixed interim prosthesis with natural tooth crown as pontic subsequent
      to replantation failure.
AB  - Facial trauma resulting in tooth avulsion results in problems of physical and
      emotional nature for the patient and a challenge for the dentist. Avulsion
      accounts for 0.5-16% of traumatic injuries in the permanent dentition that can
      occur at any age and is most common in the young permanent dentition. As an
      emergency procedure, it is advisable to replant a traumatically avulsed tooth,
      but unfortunately long-term success is rather low. After unsuccessful
      replantation and subsequent extraction, it is prudent to replace the lost tooth
      to avoid aesthetic, masticatory, and psychological difficulties and also to
      prevent arch length discrepancy with various alternatives are available for the
      same. We presented a method for management of one of the two replanted teeth that
      showed failure, using the natural crown as pontic in a fixed semi-permanent
      bridge until a more definitive prosthesis can be fabricated at a later age for
      better patient compliance.

PMID- 22144821
TI  - Mandibular first molar with three distal canals.
AB  - With the increasing number of reports of aberrant root canal morphology, the
      clinician needs to be aware of the variable anatomy. Various case reports have
      been published with the finding of middle mesial canal in mandibular first molar,
      however finding of middle distal canal in distal root of mandibular first molar
      is rare. This case report describes root canal treatment of two rooted mandibular
      first molar with five root canals (three in distal and two in mesial root), and
      Sert and Bayirli Type XVIII canal configuration in distal root.

PMID- 22144823
TI  - Two years with PubMed....

PMID- 22144822
TI  - Clinical technique for invasive cervical root resorption.
AB  - This clinical case report describes the diagnosis and treatment of an external
      invasive cervical resorption. A 17-year-old female patient had a confirmed
      diagnosis of invasive cervical resorption class 4 by cone beam computerized
      tomography. Although, there was no communication with the root canal, the
      invasive resorption process was extending into the cervical and middle third of
      the root. The treatment of the cervical resorption of the lateral incisor
      interrupted the resorptive process and restored the damaged root surface and the
      dental functions without any esthetic sequelae. Both the radiographic examination
      and computed tomography are imperative to reveal the extent of the defect in the
      differential diagnosis.

PMID- 22144824
TI  - Recurrent aphthous stomatitis.
AB  - Recurrent aphthous ulcers are common painful mucosal conditions affecting the
      oral cavity. Despite their high prevalence, etiopathogenesis remains unclear.
      This review article summarizes the clinical presentation, diagnostic criteria,
      and recent trends in the management of recurrent apthous stomatitis.

PMID- 22144825
TI  - Cancer cachexia.
AB  - Cancer cachexia is a wasting syndrome characterized by weight loss, anorexia,
      asthenia and anemia. The pathogenicity of this syndrome is multifactorial, due to
      a complex interaction of tumor and host factors. The signs and symptoms of
      cachexia are considered as the prognostic parameters in cancer patients. This
      review gives an emphasis on the various mechanisms involved in cachexia and an
      insight into head and neck cancer cachexia.

PMID- 22144826
TI  - Current concepts of immunofluorescence in oral mucocutaneous diseases.
AB  - AIM: To study the immunofluorescence pattern and to assess its reliability as a
      confirmatory diagnostic test in patients with pemphigus, pemphigoid, lichen
      planus, and lupus erythematosus and also to assess the disease activity by
      indirect immunofluorscence (IIF) in patients with pemphigus only. MATERIALS AND
      METHODS: Twenty-six patients were included in the study group, out of which, 6
      patients were clinically and histopathologically diagnosed as pemphigus,
      completely free of active lesions were subjected to IIF only to assess the
      disease activity and were grouped separately. Based on the clinical and
      provisional diagnosis, the remaining 20 patients who had active lesions were
      subjected to direct immunofluorscence (DIF) and IIF and were divided into four
      groups. Biopsy specimens were taken from the periphery of the lesions and were
      examined by both conventional light microscopic and DIF methods. Five milliliters
      of venous blood was collected from each patient and were subjected to IIF.
      RESULTS: Histopathological diagnosis was consistent with direct
      immunofluorescence study in 15 cases (75%). The various immunofluorescence
      patterns observed in our study were consistent with those described by various
      authors in standard textbooks and articles. CONCLUSION: Histopathology remains
      gold standard for most of the diseases, it is recognized from this study that not
      all lesions are amenable to definitive histopathological diagnosis thus; DIF can
      provide a valuable additional criterion in diagnosis.

PMID- 22144827
TI  - Role of mast cells in pathogenesis of oral lichen planus.
AB  - Recent attention has been directed toward the role of mast cells in the
      pathogenesis of oral lichen planus. Mast cells are responsible for trafficking
      inflammatory cells into the connective tissue that in turn helps in progression
      and maintenance of chronicity of oral lichen planus (OLP). OLP is a T-cell
      mediated chronic inflammatory oral mucosal disease of unknown etiology, and
      lesions contain few B-cells or plasma cells and minimal deposits of
      immunoglobulin or complement. Hence, OLP is ideally positioned for the study of
      human T-cell-mediated inflammation and autoimmunity. This study was done to
      evaluate the mast cell count using toluidine blue stain in OLP and compares it
      with oral lichenoid reaction (OLR), and to propose the possible role of mast
      cells in the pathogenesis of OLP and OLR. Ten cases each of OLP and OLR and five
      cases of normal buccal mucosa were taken from the archives of Department of Oral
      Pathology. The samples were stained with toluidine blue using standard toluidine
      blue method by Wolman 1971. An increase in mast cell count was observed in OLP
      and OLR in comparison to normal oral mucosa. However, no significant differences
      in mast cell count were noted between OLP and OLR.

PMID- 22144828
TI  - alpha4beta1 integrin-dependent cell sorting dictates T-cell recruitment in oral
      submucous fibrosis.
AB  - AIM: The biological mechanism(s) that guide the immunological effectors of
      lymphocytes to sites of inflammatory response, a feature consistently seen in
      oral submucous fibrosis (OSF) was evaluated. It is envisaged that
      endothelial/lymphocyte adhesion cascades involving VCAM-1/alpha4beta1 integrins
      control the migration of lymphocytes across the vascular endothelium resulting in
      their homing in these locales. MATERIALS AND METHODS: The study group comprised
      28 OSF cases (M:F = 12:16, age range 18-65 years; mean 55.4 +/- 8.5 SD) divided
      into early (n=17) and advanced (n=11) disease groups. Biopsy specimens of normal
      buccal mucosa (site compatible) were obtained from 10 healthy volunteers (age and
      sex matched) who served as control. All the samples were fixed in 10% neutral
      buffered formalin and embedded in paraffin. Immunolocalization of beta1 subunit
      associated with alpha4 integrin was performed by a mouse heterodimer (clone 4B7R,
      Ig G, R & D Systems Inc., dilution 1:100) using a peroxidase labeled streptavidin
      biotin technique. The immunocompetent cell density was expressed as the number of
      positive cells per mm(2). The Mann-Whitney U-test and Fischer exact test were
      used to evaluate differences. P<0.05 was considered to be significant. RESULTS:
      The median percentage of "T" lymphocytes with positive integrin alpha4beta1
      expression was 77.7 (an interquartile range of 73.3-83.4) for the test cases and
      for the controls, it was 28.2 (IQR 24.0-38.3). This difference was significant at
      0.001 level. For the endothelial cells the positive expression was 82.8 (IQR 77
      90.6) and 22.3 (IQR 18.3-29.2) respectively (P<0.001). When the intensity of
      integrin expression was considered 26/28 cases (96%) and 2/10 (20%) of controls
      showed intense expression of integrins alpha4beta1 on T lymphocytes (P<0.001).
      Similarly, 27/28 cases (92.9%) and 2/10 (20%) of controls showed intense
      expression on endothelial cells (P<0.001). T lymphocyte-endothelial cell
      interactions were assessed by evaluating the overexpression of integrins on both
      the endothelial cells and lymphocytes together. The interaction was positive in
      15/17 and 11/11 early and advanced OSF cases respectively (P=0.51). CONCLUSION:
      Following leukocyte activation, the interaction between leukocyte integrin
      heterodimers and endothelial superfamily adhesion ligands results in a firm
      adherence of leukocytes to endothelium, leading to leukocyte migration and homing
      to sites of mucosal inflammation consistently seen in OSF.

PMID- 22144829
TI  - Comparison of the frequency of sister chromatid exchange in pan chewers and oral
      submucous fibrosis patients.
AB  - Sister chromatid exchange (SCE) test is a sensitive, biomarker of genotoxic
      substances. The frequency of SCE in lymphocytes of ten pan chewing patients, oral
      submucous fibrosis (OSF) patients and age matched healthy controls were
      investigated. The frequency of mean SCE/cell was found to be 10.428 +/- 0.755 in
      OSF patients, 8.752 +/- 0.383 in case of pan chewers as compared to 5.912 +/-
      0.310 in controls. These values show a significant increase in frequency of
      SCE/cell in OSF patients and pan chewers when compared with that of healthy
      controls. There is a positive correlation co-efficient of SCE/cell with
      frequency, quantity, duration, intensity and period of exposure of pan-parag to
      oral mucosa in pan chewers and OSF patients indicating genotoxic effect of pan.
      Thus SCE could be used as a biomarker in chewers also to assess the level of
      genomic damage and to advocate efficient control measures.

PMID- 22144830
TI  - Immunohistochemical expression of cyclin D1 in ameloblastomas and adenomatoid
      odontogenic tumors.
AB  - BACKGROUND: Cyclin D1, a member of G1 cyclins, controls the cell-cycle transit
      from the G1 to S phase. The deregulation and overexpression of cyclin D1 has been
      revealed in many tumors of diverse histogenesis. Ameloblastoma is the most
      frequently encountered odontogenic tumor known for its local invasiveness and a
      high tendency to recur. The adenomatoid odontogenic tumor is a benign,
      nonaggressive tumor with a limited growth and no tendency to recur. AIM: The aim
      was to investigate whether the immunohistochemical expression of cyclin D1 as a
      proliferation marker in ameloblastoma and adenomatoid odontogenic tumor
      correlates with the known clinical behavior of these two benign neoplasms.
      MATERIALS AND METHODS: Ameloblastoma cases consisted of follicular, plexiform,
      and unicystic subtypes. The positive staining was assessed based on intensity of
      staining, localization of staining, and in different cell types in both the
      tumors. Two cases of follicular ameloblastoma and one case of plexiform
      ameloblastoma showed intense staining, but the predominant staining intensity was
      overall mild in both ameloblastoma and adenomatoid odontogenic tumors. The
      immunoreactivity was found both in nucleus and cytoplasm in ameloblastoma and
      only nuclear in adenomatoid odontogenic tumors. The peripheral columnar and
      central stellate reticulum-like cells of ameloblastoma showed immunoreactivity
      with squamous and granular cells being negative. In adenomatoid odontogenic
      tumors, the whorls showed predominant localization of staining. Statistical
      comparison with a Mann-Whitney U-test showed no significant difference in
      staining intensities between different histologic subtypes of ameloblastomas and
      also between ameloblastoma and adenomatoid odontogenic tumors (P>0.005).
      CONCLUSION: The marked expression of cyclin D1 in these tumors suggested its
      participation in proliferation of both the tumors and its expression patterns
      were irrespective of their known biologic behavior.

PMID- 22144831
TI  - The expression of E-cadherin and cathepsin-D in normal oral mucosa, oral
      epithelial dysplasia and oral squamous cell carcinoma: A comparative analysis
      between immunohistochemistry and routine histopathology.
AB  - BACKGROUND: E-cadherin is known to be an invasion suppressor gene and cathepsin
      D, a protease, which is an invasion promoter and plays a central role in solid
      tumors including oral cancer. AIMS: To look for the expression pattern in normal
      buccal mucosa, dysplastic oral epithelium and oral squamous cell carcinoma (SCC)
      along with their correlation to individual atypical features, thereby providing
      an objective to the grading system in predicting the fate of affected epithelium.
      MATERIALS AND METHODS: To elucidate the expression patterns of these markers, we
      examined immunohistochemically on formalin fixed, paraffin embedded sections 22
      dysplastic epithelia, eight SCC and ten normal buccal mucosa. RESULTS: In
      dysplastic epithelium slight loss of expression of E-cadherin was noted as grade
      of dysplasia increased. Two cases of carcinoma clearance showed only basal and
      suprabasal staining. The staining varied in SCC with patchy to complete absence
      of expression. With cathepsin-D fine to moderate granular cytoplasmic staining
      was noted in most of the dysplastic epithelium. Similar staining was noted in
      SCC. The atypical features which strongly correlated to loss of expression of E
      cadherin and intense cathepsin-D expression are basilar hyperplasia, loss of
      cohesion, mitosis, loss of polarity and drop shaped rete ridges. CONCLUSIONS: The
      result of the study shows that the above atypical features should be given more
      weightage in addition to traditional grading system, in predicting the fate of
      affected epithelium. Additional studies with larger sample size and using
      monoclonal antibody against cathepsin-D may further strengthen our findings.

PMID- 22144832
TI  - Maxillary keratocystic odontogenic tumor with calcifications: A review and case
      report.
AB  - Calcifications or hard tissue deposits in the wall of keratocystic odontogenic
      tumor (KCOT) are rare and uncommon. Three types of calcifications have been
      reported in the literature: dystrophic, cartilagenous, dentinoid. A case of
      maxillary KCOT with calcification is reported with a review on prevalence and
      pathogenesis of these calcifications. The calcifications associated with the
      connective tissue of keratocystic odontogenic tumor were studied using special
      stains. These calcifications were positive for collagen stains, Van Gieson,
      Masson trichrome, and negative for congo red and mallory suggesting that these
      irregularly shaped, diffuse calcifications which form on a collagenous matrix are
      dysplastic dentin.

PMID- 22144833
TI  - "Hybrid" lesion of the maxilla.
AB  - Juvenile ossifying fibroma is an uncommon benign but aggressive fibroosseous
      lesion that affects the craniofacial skeleton. Their distinct clinical and
      histopathological features warrant the lesion to be considered as a separate
      entity from other fibro-osseous group of lesions such as fibrous dysplasia and
      cemento ossifying fibroma. Concomitant development of secondary aneurysmal bone
      cyst may rarely occur, which makes the lesion more aggressive and difficult to
      treat. We report a case of a 6 year old girl who was diagnosed with aneurysmal
      bone cyst during her earlier presentation at a private hospital and was treated
      for the same. The lesion recurred within 6 months. The second incisional biopsy
      specimen revealed features of trabecular variant of juvenile ossifying fibroma
      along with areas of aneurysmal bone cyst.

PMID- 22144834
TI  - Ameloblastic fibroma in six-year-old male: Hamartoma or a true neoplasm.
AB  - Ameloblastic fibroma (AF) is an uncommon true mixed odontogenic tumor with a
      relative frequency between 1.5% and 4.5%. Recently, it has been proposed that two
      subtypes of AF exist: A neoplasm and a hamartomatous lesion. We report a case of
      AF in left mandibular posterior region in a 6-year-old male patient. The tumor
      showed unusual and aggressive features that suggested it was a true neoplasm.

PMID- 22144835
TI  - A case of dual malignancy: Presenting the necessity for extensive sampling for
      pathologic examination.
AB  - A patient diagnosed with early squamous-cell carcinoma (SCC) with microinvasion
      was treated by surgical excision followed by histopathologic evaluation. During
      surgery, all the nodes appeared free of tumor other than a single level-3 node
      which looked suspicious and enlarged. Surprisingly, the node, instead of showing
      SCC showed features suggestive of "etastatic papillary thyroid carcinoma." The
      characteristics of papillary thyroid carcinoma (PTC), their usual histopathologic
      features and treatment are discussed. The aim of this paper is to present the
      case of a patient with dual malignancy-oral SCC and PTC in an adult male, which
      was diagnosed accidently because the protocol of complete surgery and extensive
      sampling for pathologic examination was followed and thus emphasizes on the
      necessity for the same.

PMID- 22144836
TI  - Symmetric palatal swelling as the first clinical manifestation of a mantle cell
      non-Hodgkin's lymphoma: A case report and review of literature.
AB  - The mantle cell lymphoma (MCL) is a rare (3.7%) low-grade non-Hodgkin lymphoma
      originating from the B-cell precursor-subpopulation. The clinical appearance in
      the oral cavity is rare. Since 1980, nine cases have been reported. A 41-year-old
      patient showed a MCL presenting with a symmetric, painless palatal swelling
      without any other clinical symptoms. Histological sections revealed malignant
      monotonous lymphoid cells (CD20+, CD43+, Ki67+) and the typical cyclinD1 over
      expression by the chromosomal translocation t(11;14)(q13;q32). The proliferating
      cells weekly expressed CD5, kappa-and lambda-light chains and no EMA, CD10, bcl
      6, CD30, and CD23. The patient was treated according to the European MCL younger
      study, and the MCL is regressive. The high incidence of dento-alveolar abscesses,
      inflammations, or benign tumor-formations leads to associate any maxillary or
      palatal swelling with this clinical condition. Considering the serious
      consequences of a missed therapy a histological examination of any untypical
      "swelling" is demanded.

PMID- 22144837
TI  - Juvenile hemangioma: A case report with an emphasis on its clinical phases
      (evolution and involution), and immunohistochemically distinctive physiologic
      differences.
AB  - Hemangiomas occupy a grey zone between hamartomatous malformations and true
      neoplasms. They are frequently designated and regarded as neoplasms because of
      their usually localized nature and mass effect. Although clearly benign, they can
      become very large and unsightly, and can even be fatal if they affect vital
      structures. They almost never become malignant, although a few documented
      examples of this complication are on record. A high percentage occur in children,
      manifesting within the first month of life. One half of these cases are in the
      head and neck area. Hemangiomas have been classified according to their clinical
      appearance and the caliber of vessel involved, namely, capillary, cavernous and
      venous. Capillary hemangiomas are made up of small vessels of capillary caliber.
      One such capillary hemangioma, the juvenile hemangioma (JH), is usually present
      at birth or appears during the first month and enlarges rapidly during the first
      few months of life (infancy), only to stop growing when the child is
      approximately 6 years old. We present one such JH, seen in a 3 year old male
      child, which appeared when the child was 2 months old. Routine histopathological
      (H and E) and immunohistochemical analysis (CD 34, CD 31) was done on biopsy
      received.

PMID- 22144838
TI  - Rhabdomyosarcoma of mandible: A diagnostic predicament.
AB  - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children under
      15 years of age and rare among persons older than 45 years of age. It is
      considered to result from malignant transformation of primitive mesenchymal
      cells. Although it has a relative predominance for head and neck region, it is
      found less often in oral cavity. Here we report a case of RMS of mandible in an
      adult patient, which was initially diagnosed as carcinosarcoma. Clinical and
      pathologic findings are described, which were confirmed by histochemical and
      immunohistochemical stains.

PMID- 22144839
TI  - Psammomatoid juvenile ossifying fibroma of the jaws.
AB  - Juvenile ossifying fibroma is an uncommon, benign, bone-forming neoplasm with
      aggressive local growth that is distinguished from other fibro-osseous lesions
      primarily by its age of onset, clinical presentation and aggressive behavior.
      Although a benign entity, juvenile ossifying fibroma is known to be locally
      aggressive and has a high tendency to recur. Two distinctive microscopic patterns
      have been described: A trabecular variant and a psammomatoid variant. This latter
      variant is predominantly a craniofacial lesion and occurs rarely in the jaws. We
      present herein two cases of psammomatoid juvenile ossifying fibroma involving the
      jaws. The first case was a mandibular lesion in a 31-year-old female whereas the
      second case presented with maxillary involvement in a 46-year-old female. In
      addition, the pathology of the lesion was analyzed with confocal laser scanning
      microscopy.

PMID- 22144840
TI  - Small cell osteosarcoma of the mandible: Case report and review of its diagnostic
      aspects.
AB  - Small cell osteosarcoma, a rare histological subtype, has very infrequently been
      reported in the mandible. We present a case of a 28-year-old female who had
      classic signs, symptoms, and radiographic features of the lesion. The histology
      showed sheets of small round cells and osteoid. The absence of the latter would
      have made it difficult to distinguish from other small round cell tumors of bone,
      especially Ewing's sarcoma. We have reviewed the clinical and radiographic
      features, cytologic and histologic characteristics, as well as the
      immunohistochemistry and molecular genetics of small cell osteosarcoma.

PMID- 22144841
TI  - Hyalinizing clear cell carcinoma: A rare entity.
AB  - Hyalinizing clear cell carcinoma (HCCC) is an uncommon malignant salivary gland
      tumor accounting for about 1% of all intra-oral salivary gland tumors.
      Microscopic diagnosis of clear cell carcinoma may be challenging because of the
      spectrum of features which frequently overlaps with the other salivary gland
      tumors that contain clear cells, and thus it may be a diagnosis of exclusion.
      Here we, report a case of HCCC in a 36 years old female with detailed
      histological, histochemical and immunohistochemical discussion.

PMID- 22144842
TI  - Extensive gingival myiasis - Diagnosis, treatment, and prevention.
AB  - Myiasis is a rare disease primarily caused by infestation of tissue by larvae of
      houseflies. Oral myiasis is still more "rare" and "unique" owing to the fact that
      oral cavity rarely provides the necessary habitat conducive for a larval
      lifecycle. Here we report a case of extensive gingival myiasis, in an 81-year-old
      female patient, diagnosed and treated successfully in our department. The case is
      discussed in relation to its clinical presentation, etiopathogenesis, management,
      and prognosis.

PMID- 22144843
TI  - Inflammatory pseudotumor of maxillary sinus: Mimicking as an aggressive
      malignancy.
AB  - Inflammatory pseudotumor is a rare entity in the head and neck region. Clinically
      it behaves as an aggressive lesion with extensive destruction but considered to
      be a benign reactive process. Because of its extensive involvement and
      infiltrative nature, it is confused as a malignancy. Most of them respond very
      well to corticosteroid and surgical excision.

PMID- 22144844
TI  - Tooth in oropharynx.
AB  - The incidence of ectopic teeth has increased. In many cases, the etiology of
      ectopic teeth cannot be identified. Ectopic tooth in deciduous dentition period
      is very rare and information is limited about its causes and characteristics. The
      conditions commonly associated with an increased prevalence of ectopic teeth
      include cleft lip and palate, cleidocranial dysplasia, and Gardner syndrome. The
      diagnosis is made by the clinical and radiological examinations. The indication
      for extraction in ectopic teeth cases is in general determined by the presence of
      symptomatology, or by the need for preventing future complications. We present a
      case of an ectopic maxillary tooth in a 4 year-old boy. In addition, this report
      also addresses a young patient with a tooth in the oropharynx with the objective
      of non traumatic etiology, and such a clinical presentation is extremely rare.
      The authors believe the case presented here is the first documented case of an
      ectopic supernumerary tooth seen in the oropharynx.

PMID- 22144845
TI  - Treacher Collins syndrome.
AB  - Treacher Collins syndrome (TCS) is a rare autosomal dominant disorder of
      craniofacial development. It is a congenital malformation of first and second
      branchial arch which may affect the size and shape of the ears, eyelids, cheek
      bones, and jaws. The extent of facial deformity varies from one affected
      individual to another. A case of 20-year-old boy having TCS is briefly described
      in this article.

PMID- 22144846
TI  - Papillon-Lefevre syndrome.
AB  - The goal of periodontal therapy has always been regeneration of the lost tissues.
      However, conventional periodontal therapy has not always been successful in
      achieving regeneration, especially when it is part of a syndrome. This case
      report involves a 13-year old male patient with the chief complaint of mobile
      teeth for over 3 months. His dental history revealed early loss of primary
      dentition, around 3-4 years of age and that he noticed mobility of permanent
      incisors and molars at 9-10 years. Keratotic skin lesions on the palms and soles
      were present since the age of 3 years. Full mouth intra-oral periapical
      radiographs showed extensive bone loss upto apical thirds of the teeth and an
      orthopantamograph showed "floating in air" appearance. Further, a lateral
      cephalogram was taken to rule out any calcifications of the duramater. The case
      was provisionally diagnosed to be Papillon Lefevre syndrome. A conventional
      polymerase chain reaction assay was also done to assess the virulence genes in
      aggressive periodontitis. Though the management of PLS involves the regular
      phases of periodontal therapy, namely, etiotropic, surgical, restorative and
      maintenance phases, the complete esthetic and functional rehabilitation also
      involves other specialities especially prosthodontic and dermatologic and later
      an implantologist. After appropriate periodontal and prosthodontic management,
      the patient has been followed up for over a year and is maintaining in a stable
      condition.

PMID- 22144847
TI  - Benign cementoblastoma.
AB  - Benign cementoblastoma is a rare odontogenic tumor characterized by the formation
      of a mass of cementum or cementum-like tissue attached to the roots of a tooth.
      Cementoblastoma are distinctive but relatively uncommon tumors. The clinical,
      radiographic, and histopathologic features of a case of benign cementoblastoma
      are presented in this paper along with a brief review of the literature.

PMID- 22144848
TI  - Oral leiomyoma.
AB  - Oral leiomyoma is a benign smooth muscle tumor with a low incidence. Oral
      leiomyomas present as slow growing, asymptomatic sub mucosal masses, usually in
      the tongue, hard palate or buccal mucosa. They may be seen at any age and are
      usually discovered when they are 1 to 2 cm in diameter. The diagnosis is mainly
      determined by histological studies and special stains that confirm the smooth
      muscle origin. Surgical excision appears to be the best line of treatment and
      recurrence is unexpected. The purpose of this article is to present a case of a
      32-year old male with a 1 month history of a leiomyoma on his right submandibular
      region.

PMID- 22144849
TI  - Detection of pelvic inflammatory disease: development of an automated case
      finding algorithm using administrative data.
AB  - ICD-9 codes are conventionally used to identify pelvic inflammatory disease (PID)
      from administrative data for surveillance purposes. This approach may include non
      PID cases. To refine PID case identification among women with ICD-9 codes
      suggestive of PID, a case-finding algorithm was developed using additional
      variables. Potential PID cases were identified among women aged 15-44 years at
      Group Health (GH) and Kaiser Permanente Colorado (KPCO) and verified by medical
      record review. A classification and regression tree analysis was used to develop
      the algorithm at GH; validation occurred at KPCO. The positive predictive value
      (PPV) for using ICD-9 codes alone to identify clinical PID cases was 79%. The
      algorithm identified PID appropriate treatment and age 15-25 years as predictors.
      Algorithm sensitivity (GH = 96.4%; KPCO = 90.3%) and PPV (GH = 86.9%; KPCO =
      84.5%) were high, but specificity was poor (GH = 45.9%; KPCO = 37.0%). In GH, the
      algorithm offered a practical alternative to medical record review to further
      improve PID case identification.

PMID- 22144850
TI  - Are dual-method messages undermining STI/HIV prevention?
AB  - Adolescent girls and young women who are at risk for unplanned pregnancy and
      sexually transmitted infection (STI), including HIV, are frequently counseled to
      use a hormonal contraceptive to protect against the former and condoms to protect
      against the latter, for example, American College of Obstetricians and
      Gynecologists, 2011. The present paper reviews the literature on multiple risk
      messages, compliance with this dual-use recommendation, predictors of dual use,
      and interventions developed to encourage dual use. Data indicate that
      simultaneous use of these two methods is not common, and that efforts to
      encourage dual use have not yielded promising results. An alternative is to
      recommend condom use alone, since condoms protect very well against STI and HIV,
      and quite well against pregnancy when used consistently and correctly. The
      availability of emergency contraception is relevant here. Research utilizing a
      randomized controlled trial is recommended.

PMID- 22144852
TI  - Annotated type catalogue of the Amphibulimidae (Mollusca, Gastropoda,
      Orthalicoidea) in the Natural History Museum, London.
AB  - The type status is described of 39 taxa classified within the family
      Amphibulimidae (superfamily Orthalicoidea) and kept in the London museum. One
      taxon, Bulimus elaeodes Pfeiffer, 1853, is removed to the Strophocheilidae.
      Lectotypes are designated for Bulimus adoptus Reeve, 1849; Bulimus (Eurytus) eros
      Angas, 1878; Helix onca d'Orbigny, 1835; Amphibulima pardalina Guppy, 1868. The
      type status of the following taxon is changed to lectotype in accordance with
      Art. 74.6 ICZN: Strophocheilus (Dryptus) jubeus Fulton, 1908.As general
      introduction to this and following papers on Orthalicoid types in the Natural
      History Museum, a brief history of the London collection is given and several
      examples of handwriting from different authors are presented.

PMID- 22144853
TI  - A new species of hydrobiid snails (Mollusca, Gastropoda, Hydrobiidae) from
      central Greece.
AB  - Anew minute valvatiform species belonging to the genus Daphniola Radoman, 1973,
      Daphniola eptalophossp. n., from mountain Parnassos, Greece is described. The new
      species has a transparent valvatiform-planispiral shell, wide and open umbilicus,
      grey-black pigmented soft body and head and a black penis with a small colorless
      outgrowth on the left side near its base. A comparative table of shell dimensions
      and a key to the species known for this endemic genus for Greece are provided.

PMID- 22144851
TI  - Chlamydia trachomatis infection control programs: lessons learned and
      implications for vaccine development.
AB  - Chlamydia trachomatis control efforts that enhance detection and treatment of
      infected women may paradoxically increase susceptibility of the population to
      infection. Conversely, these surveillance programs lower incidences of adverse
      sequelae elicited by genital tract infection (e.g., pelvic inflammatory disease
      and ectopic pregnancy), suggesting enhanced identification and eradication of C.
      trachomatis simultaneously reduces pathogen-induced upper genital tract damage
      and abrogates formation of protective immune responses. In this paper, we detail
      findings from C. trachomatis infection control programs that increase our
      understanding of chlamydial immunoepidemiology and discuss their implications for
      prophylactic vaccine design.

PMID- 22144854
TI  - A new species of Diochus from Baltic amber (Coleoptera, Staphylinidae, Diochini).
AB  - The first fossil of the staphylinine tribe Diochini Casey is described and
      figured from an inclusion in mid-Eocene (Lutetian) Baltic amber. Diochus
      electrussp. n. is distinguished from its congeners and the diversity of rove
      beetles (Staphylinidae s.l.) is summarized briefly.

PMID- 22144855
TI  - Iranotrichia gen. n., a new genus of Scenopinidae (Diptera) from Iran, with a key
      to window fly genera of the world.
AB  - An unusual new genus of Scenopinidae, Iranotrichia gen. n., comprising two newly
      discovered species (Iranotrichia insolitasp. n. and Iranotrichia nigrasp. n.), is
      described from Iran. Iranotrichiagen. n. are scenopinine window flies with a
      habitus reminiscent of certain bee fly genera (Bombyliidae), based on colouration
      and elongate mouthparts and antennae. The phylogenetic placement of this
      distinctive new genus is discussed and a dichotomous key to world genera is
      presented. The genus name Kelseyananom. n. is proposed to replace Caenoneura
      Krober, 1924, which was found to be preoccupied by Thomson (1870: 270)
      (Hymenoptera) and Kirby (1890: 136) (Odonata).

PMID- 22144856
TI  - On a new Dictyna species (Araneae, Dictynidae) from the northern Palaearctic
      confused with the East Siberian D. schmidti Kulczynski, 1926.
AB  - A new species, Dictyna palmgrenisp. n., is described from Finland and Russia on
      the basis of both sexes. Most of the earlier records of Dictyna schmidti
      Kulczynski, 1926 from the northern Palaearctic refer to this new species. Dictyna
      shilenkovi Danilov, 2000, syn. n. from Cisbaikalia is synonymised with Dictyna
      schmidti. The general appearances and copulatory organs of Dictyna palmgrenisp.
      n., Dictyna schmidti and Dictyna major Menge, 1869 are illustrated. The
      distribution of Dictyna palmgrenisp. n. andDictyna schmidti is clarified. An
      unknown sac-like structure of the spermathecae of Dictyninae is briefly
      discussed.

PMID- 22144857
TI  - Black-tie dress code: two new species of the genus Toxomerus (Diptera,
      Syrphidae).
AB  - Toxomerus hauseri Mengual sp. n. and Toxomerus picudus Mengual sp. n. are
      described from Peru and Ecuador respectively. Toxomerus circumcintus (Enderlein,
      1938) is treated as a valid species and not considered synonym of Toxomerus
      marginatus, and Toxomerus ovatus (Hull, 1942) is considered junior synonym of
      Toxomerus nitidus (Schiner, 1868). An identification key for the Toxomerus
      species with dark abdomens is given along with diagnoses for each studied
      species.

PMID- 22144858
TI  - Revision of the orchid bee subgenus Euglossella (Hymenoptera, Apidae), Part I,
      The decorata species group.
AB  - Euglossella, one of the most distinctive subgenera of orchid bees of the genus
      Euglossa, is composed of two characteristic assemblages of species, one of them
      comprising bees bearing the strongly metallic integument trademark of the genus
      (viridis species group), and the other consisting of bees with a brown integument
      shaded with metallic iridescence (decorata species group). Here we provide the
      first of two parts of a revision of Euglossella, providing diagnostic definitions
      for the subgenus, the decorata species group, and all the species included
      therein. Six species are included in the decorata group, one new: Euglossa
      (Euglossella) aurantia, sp. n.; Euglossa (Euglossella) apiformis Schrottky,
      resurrected status; Euglossa (Euglossella) decorata Smith, revised status;
      Euglossa (Euglossella) singularis Mocsary, revised status; Euglossa (Euglossella)
      cosmodora Hinojosa-Diaz and Engel; and Euglossa (Euglossella) perpulchra Moure
      and Schlindwein. Euglossa meliponoides Ducke and Euglossa urarina Hinojosa-Diaz
      and Engel are newly synonymized under Euglossa decorata, Euglossa decorata
      ruficauda Cockerell is synonymized under Euglossa singularis, and a neotype is
      designated for Euglossa apiformis.

PMID- 22144859
TI  - Triteleia peyerimhoffi comb. n., a remarkably variable circum-Mediterranean
      scelionid (Hymenoptera, Platygastroidea).
AB  - Triteleia peyerimhofficomb. n. (Kieffer, 1906) is redescribed taking into account
      its great variability and is considered the senior synonym of Triteleia dubia
      (Kieffer, 1908), Calliscelio lugens (Kieffer, 1910) and Triteleia striolata
      Kononova & Petrov, 2000, syn. n. Neotypes are designated for Triteleia dubia and
      Triteleia peyerimhoffi. Triteleia peyerimhoffi is a new record for Greece, France
      and Croatia and was reared for the first time from eggs of Orthoptera laid in the
      dead wood of Quercus sp. and Tilia sp. in Romania.

PMID- 22144860
TI  - First records of Gastrotricha from South Africa, with description of a new
      species of Halichaetonotus (Chaetonotida, Chaetonotidae).
AB  - During a survey of the biota of the St. Lucia Estuary in the iSimangaliso Wetland
      Park, South Africa, a number of Gastrotricha were found among samples of
      meiofauna. Fresh, marine sediment yielded several specimens belonging to a total
      of seven species. Of these, two are already known from other regions (i.e.,
      Dactylopodola australiensis and Heteroxenotrichula squamosa), one is described as
      new to science (Halichaetonotus sanctaeluciae sp. n.), while the remaining four
      (Pseudostomella sp., Halichaetonotus sp.1, Halichaetonotus sp. 2, Xenotrichula
      sp.) require further collections and analysis, in order to establish the extent
      of their affiliation to species already described. General appearance, shape of
      hydrofoil scale and the occurrence of three long spines on the dorsal side make
      the new species most closely related to Halichaetonotus australis and
      Halichaetonotus marivagus. The key differences from these taxa and between
      Halichaetonotus sanctaeluciae sp. n. and Halichaetonotus aculifer are discussed.

PMID- 22144861
TI  - Taxonomic contribution to the Aleiodes melanopterus (Erichson) species-group
      (Hymenoptera, Braconidae, Rogadinae) from Brazil.
AB  - The Aleiodes melanopterus (Erichson, 1848) species-group includes 21 species, of
      which seven are known from the Neotropical region: Aleiodes flavistigma Shaw,
      1993, Aleiodes lucidus (Szepligeti, 1906), Aleiodes melanopterus, Aleiodes
      mexicanus Cresson, 1869, Aleiodes politiceps (Gahan, 1917), and the new species
      Aleiodes shaworumsp. n. and Aleiodes vassunungasp. n. Distribution ranges of
      Aleiodes melanopterus, Aleoides flavistigma and Aleiodes lucidus are extended and
      the female of Aleiodes lucidus is described. A key to the Neotropical species of
      this species-group is presented.

PMID- 22144862
TI  - Revision of the new world genus Crassomicrodus Ashmead (Hymenoptera, Braconidae,
      Agathidinae), with an identification key to species.
AB  - A key to species and descriptions are presented for 14 species of the New World
      genus Crassomicrodus Ashmead. Seven new species, Crassomicrodus azteca,
      Crassomicrodus clypealis, Crassomicrodus costaricensis, Crassomicrodus
      jalisciensis, Crassomicrodus mariae, Crassomicrodus oaxaquensis,and
      Crassomicrodus olgae are described. Crassomicrodus fenestratus (Viereck) is
      synonymized with Crassomicrodus nigriceps (Cresson). Crassomicrodus melanopleurus
      (Ashmead) is recognized as a valid species.

PMID- 22144863
TI  - Redescription of Platygyndes Roewer 1943, a false Gonyleptidae, (Arachnida,
      Opiliones, Cosmetidae).
AB  - Praelibitia Roewer, 1956 and its type species, Praelibitia titicaca Roewer, 1956,
      are respectively synonymized with Platygyndes Roewer, 1943 and its type species
      Platygyndes titicaca Roewer, 1943, and furthermore the genus is transferred from
      the Gonyleptidae to the Cosmetidae. On the basis of domed and unarmed ocularium,
      increased number of granules on scutal areas, unarmed dorsal scutum and general
      body shape, Platygyndes seems to be closely related to Moselabius Roewer, 1956
      and Caracarana Roewer, 1956. External morphological characters that are useful to
      revealing relationships among cosmetid genera are discussed.

PMID- 22144864
TI  - A new species of the genus Hydrodroma Koch, 1837 (Acari, Hydrachnidia,
      Hydrodromidae), with a key to the hitherto known six species of the genus in
      Australia.
AB  - The genus Hydrodroma Koch, 1837 in Australia consists of six species, the newly
      described Hydrodroma meridionalissp. n. included. The new species is described
      from 45 sampling sites from running waters in Queensland, Victoria, New Southern
      Wales, Western Australia, Northern Territory and South Australia. Furthermore, a
      key for the identification of species of Hydrodroma occurring in Australia is
      given.

PMID- 22144865
TI  - Nine eriophyoid mite species from Iran (Acari, Eriophyidae).
AB  - Nine eriophyoid mites, including two new species and five new records, from Iran
      are described and illustrated. They are Aceria acroptiloni Shevchenko & Kacalev,
      1974, rec. n. on Rhaponticum repens (L.) Hidalgo (Asteraceae); Aceria anthocoptes
      (Nalepa, 1892), rec. n. on Cirsium arvense (L.) Scop. (Asteraceae); Aceria
      lactucae (Canestrini, 1893), rec. n. on Lactuca virosa L. (Asteraceae); Aceria
      pulicarissp. n. on Pulicaria gnaphalodes (Vent.) Boiss. (Asteraceae); Aceria
      tosichella Keifer, 1969 on Setaria viridis (L.) Beauv. (Poaceae); Eriophyes
      rotundae Mohanasundaram, 1983 on Cyperus rotundus L. (Cyperaceae); Aculops
      maroccensis Keifer, 1972, rec. n. on Mentha piperita L. (Lamiaceae); Aculus
      medicagersp. n. on Medicago sativa L. (Leguminosae); Tetra lycopersici Xue &
      Hong, 2005, rec. n. on Solanum nigrum L. (Solanaceae).

PMID- 22144866
TI  - The genus Anthia Weber in the Republic of South Africa, Identification,
      distribution, biogeography, and behavior (Coleoptera, Carabidae).
AB  - A key is presented for the identification of the four species of Anthia Weber
      (Coleoptera: Carabidae) recorded from the Republic of South Africa: Anthia
      cinctipennis Lequien, Anthia circumscripta Klug, Anthia maxillosa (Fabricius),
      and Anthia thoracica (Thunberg). For each of these species, illustrations are
      provided of adult beetles of both sexes as well as illustrations of male
      reproductive structures, morphological redescriptions, discussions of
      morphological variation, annual activity histograms, and maps of occurrence
      localities in the Republic of South Africa. Maps of occurrence localities for
      these species are compared against ecoregional and vegetation maps of southern
      Africa; each species of Anthia shows a different pattern of occupancy across the
      suite of ecoregions and vegetation types in the Republic of South Africa.
      Information about predatory and foraging behaviors, Mullerian mimicry, and small
      scale vegetation community associations is presented for Anthia thoracica based
      on field and laboratory studies in Kruger National Park, South Africa.

PMID- 22144867
TI  - Taxonomic notes on Lasioglossum (Lasioglossum) subopacum (Smith) and L. (L.)
      okinawa Ebmer et Maeta (Hymenoptera, Halictidae) from Asia.
AB  - Lasioglossum (Lasioglossum) subopacum (Smith) is recorded from the Korean
      Peninsula for the first time. Lasioglossum (Lasioglossum) okinawa Ebmer et Maeta
      from Japan is ranked to a subspecies of Lasioglossum (Lasioglossum) subopacum
      judging from the characteristics of the male. The male of Lasioglossum
      (Lasioglossum) subopacumokinawa is described for the first time. Some bionomical
      notes of both subspecies are presented.

PMID- 22144868
TI  - Welcome to saigon.

PMID- 22144869
TI  - A decade of the asian regional cooperative council for nuclear medicine: a path
      to reduce heterogeneity of nuclear medicine practice in Asia.

PMID- 22144870
TI  - Improved quality of life in patients treated with Peptide radionuclides.
AB  - Peptide receptor radionuclide therapy (PRRT) has recently been established as an
      important treatment modality for somatostatin receptor (SSTR)-positive tumors.
      The purpose of this study was to evaluate the clinical response, side-effects as
      well as the quality of life following (90)Y-DOTA-lanreotide (DOTALAN) and/or
      (90)Y-DOTA-Tyr (3)-DPhe(1)-octreotide (DOTATOC) therapy in patients with
      progressive metastatic disease during a 6-year follow-up period. Following
      dosimetric evaluation with (111)In-DOTALAN and (111)In-DOTATOC, 13 patients with
      estimated absorbed tumor doses of >5 Gy/GBq (carcinoid, n = 5; radioiodine
      negative thyroid cancer, n = 4; gastrinoma, n = 1; insulinoma, n = 1;
      glucagonoma, n = 1; glomus jugularis tumor, n = 1) were assigned for PRRT. A dose
      of 925 MBq of (90)Y-DOTALAN (four patients) or 1.85-3.7 GBq of (90)Y-DOTATOC (10
      patients) was administered intravenously and repeated every 4-8 weeks. Tumor
      dosimetry was performed prior to and under therapy, re-staging every 2-3 months.
      Pain intensity, Karnofsky score and general symptoms were evaluated in order to
      determine quality of life. Patients were followed until death. Altogether, 53
      infusions of PRRT (1.85-14.1 GBq) were administered. After the first follow-up of
      3 months of (90)Y-DOTALAN therapy, stable disease (SD) was observed in one
      patient and progressive disease (PD) in three patients. With (90)Y-DOTATOC
      therapy, SD was found in all 10 patients. During the re-evaluation period (4-27
      months), one patient had to be shifted from (90)Y-DOTALAN to (90)Y-DOTATOC
      therapy due to reduced (111)In-DOTALAN uptake after 5.5 GBq. In the first 6
      months after PRRT with DOTATOC, SD was found in nine of 10 patients and PD in one
      patient. Thereafter, SD was observed in two patients and PD in eight patients.
      Nine of 13 patients after PRRT with either DOTALAN or DOTATOC died. None of the
      patients had experienced severe acute hematological side-effects. Transient
      thrombocytopenia or lymphocytopenia was seen in 10 patients after 3.7 GBq, and a
      skin reaction in one patient. Total accumulated kidney dose ranged between 4 and
      64 Gy, with reduced creatinine clearance in two patients. Pain relief was
      achieved in three of three patients after ~3.7 GBq ERT within 4-6 months.
      Appetite, weight, Karnofsky score and general well-being had improved in patients
      with SD during and after therapy. Based on the results of this study conducted on
      a small group of patients, we conclude that PRRT may offer an alternative
      treatment option for SSTR-positive tumors, with only mild transient side-effects
      and a marked improvement in the quality of life.

PMID- 22144871
TI  - Dosimetric considerations in radioimmunotherapy and systemic radionuclide
      therapies: a review.
AB  - Radiopharmaceutical therapy, once touted as the "magic bullet" in radiation
      oncology, is increasingly being used in the treatment of a variety of
      malignancies; albeit in later disease stages. With ever-increasing public and
      medical awareness of radiation effects, radiation dosimetry is becoming more
      important. Dosimetry allows administration of the maximum tolerated radiation
      dose to the tumor/organ to be treated but limiting radiation to critical organs.
      Traditional tumor dosimetry involved acquiring pretherapy planar scans and plasma
      estimates with a diagnostic dose of intended radiopharmaceuticals. New
      advancements in single photon emission computed tomography and positron emission
      tomography systems allow semi-quantitative measurements of radiation dosimetry
      thus allowing treatments tailored to each individual patient.

PMID- 22144872
TI  - Bone Scan "Hot Spot" at the Superior Lateral Orbital Margin Fronto-zygomatic
      Suture Uptake Characterized with Tc-99m MDP SPECT/CT.
AB  - Findings of a solitary "hot spot" at the superior lateral orbital margin on bone
      scan scintigraphy is not uncommonly seen, and is often dismissed as a benign
      lesion. However, the exact etiology is indeterminate. We present two cases in
      which hybrid single photon emission computed tomography/computed tomography
      imaging was able to characterize and localize this uptake, demonstrating
      correlation to the right fronto-zygomatic suture.

PMID- 22144873
TI  - Attention to context: U.S. and Japanese children's emotional judgments.
AB  - A growing number of studies suggest cultural differences in the attention and
      evaluation of information in adults (Masuda & Nisbett, 2001; Markus & Kitayama,
      1991; Hedden, Ketay, Aron, Markus, & Gabrieli, 2008). One cultural comparison,
      between Westerners, such as Americans, and Easterners, such as the Japanese,
      suggest that Westerners typically focus on a central single object in a scene
      while Easterners often integrate their judgment of the focal object with
      surrounding contextual cues. There are few studies of whether such cultural
      differences are evident in children. This study examined 48 monolingual Japanese
      speaking children residing in Japan and 48 monolingual English-speaking children
      residing in the U.S.A. (40 to 60 month-olds) in a task asking children to
      complete a picture by adding the proper emotional expression to a face. The key
      variable was the context and shift in context from the preceding trial for the
      same pictured individual. Japanese children were much more likely to shift their
      judgments with changes in context whereas children from the United States treated
      facial expression in a more trait-like manner, maintaining the same expression
      for the individual across contexts.

PMID- 22144874
TI  - Comparative microbial modules resource: generation and visualization of multi
      species biclusters.
AB  - The increasing abundance of large-scale, high-throughput datasets for many
      closely related organisms provides opportunities for comparative analysis via the
      simultaneous biclustering of datasets from multiple species. These analyses
      require a reformulation of how to organize multi-species datasets and visualize
      comparative genomics data analyses results. Recently, we developed a method,
      multi-species cMonkey, which integrates heterogeneous high-throughput datatypes
      from multiple species to identify conserved regulatory modules. Here we present
      an integrated data visualization system, built upon the Gaggle, enabling
      exploration of our method's results (available at
      http://meatwad.bio.nyu.edu/cmmr.html). The system can also be used to explore
      other comparative genomics datasets and outputs from other data analysis
      procedures - results from other multiple-species clustering programs or from
      independent clustering of different single-species datasets. We provide an
      example use of our system for two bacteria, Escherichia coli and Salmonella
      Typhimurium. We illustrate the use of our system by exploring conserved
      biclusters involved in nitrogen metabolism, uncovering a putative function for
      yjjI, a currently uncharacterized gene that we predict to be involved in nitrogen
      assimilation.

PMID- 22144875
TI  - Validation of skeletal muscle cis-regulatory module predictions reveals
      nucleotide composition bias in functional enhancers.
AB  - We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs)
      using three computational prediction programs. Based on the predictions, 339
      candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12
      myoblasts for capacity to direct selective reporter gene expression to
      differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the
      assay. The rate of predictive success reveals striking limitations of
      computational regulatory sequence analysis methods for CRM discovery. Motif-based
      methods performed no better than predictions based only on sequence conservation.
      Analysis of the properties of the functional sequences relative to inactive
      sequences identifies nucleotide sequence composition can be an important
      characteristic to incorporate in future methods for improved predictive
      specificity. Muscle-related TFBSs predicted within the functional sequences
      display greater sequence conservation than non-TFBS flanking regions. Comparison
      with recent MyoD and histone modification ChIP-Seq data supports the validity of
      the functional regions.

PMID- 22144876
TI  - Dominant glint based prey localization in horseshoe bats: a possible strategy for
      noise rejection.
AB  - Rhinolophidae or Horseshoe bats emit long and narrowband calls. Fluttering insect
      prey generates echoes in which amplitude and frequency shifts are present, i.e.
      glints. These glints are reliable cues about the presence of prey and also encode
      certain properties of the prey. In this paper, we propose that these glints, i.e.
      the dominant glints, are also reliable signals upon which to base prey
      localization. In contrast to the spectral cues used by many other bats, the
      localization cues in Rhinolophidae are most likely provided by self-induced
      amplitude modulations generated by pinnae movement. Amplitude variations in the
      echo not introduced by the moving pinnae can be considered as noise interfering
      with the localization process. The amplitude of the dominant glints is very
      stable. Therefore, these parts of the echoes contain very little noise. However,
      using only the dominant glints potentially comes at a cost. Depending on the
      flutter rate of the insect, a limited number of dominant glints will be present
      in each echo giving the bat a limited number of sample points on which to base
      localization. We evaluate the feasibility of a strategy under which Rhinolophidae
      use only dominant glints. We use a computational model of the echolocation task
      faced by Rhinolophidae. Our model includes the spatial filtering of the echoes by
      the morphology of the sonar apparatus of Rhinolophus rouxii as well as the
      amplitude modulations introduced by pinnae movements. Using this model, we
      evaluate whether the dominant glints provide Rhinolophidae with enough
      information to perform localization. Our simulations show that Rhinolophidae can
      use dominant glints in the echoes as carriers for self-induced amplitude
      modulations serving as localization cues. In particular, it is shown that the
      reduction in noise achieved by using only the dominant glints outweighs the
      information loss that occurs by sampling the echo.

PMID- 22144877
TI  - Identifying single copy orthologs in Metazoa.
AB  - The identification of single copy (1-to-1) orthologs in any group of organisms is
      important for functional classification and phylogenetic studies. The Metazoa are
      no exception, but only recently has there been a wide-enough distribution of taxa
      with sufficiently high quality sequenced genomes to gain confidence in the wide
      spread single copy status of a gene.Here, we present a phylogenetic approach for
      identifying overlooked single copy orthologs from multigene families and apply it
      to the Metazoa. Using 18 sequenced metazoan genomes of high quality we identified
      a robust set of 1,126 orthologous groups that have been retained in single copy
      since the last common ancestor of Metazoa. We found that the use of the
      phylogenetic procedure increased the number of single copy orthologs found by
      over a third more than standard taxon-count approaches. The orthologs represented
      a wide range of functional categories, expression profiles and levels of
      divergence.To demonstrate the value of our set of single copy orthologs, we used
      them to assess the completeness of 24 currently published metazoan genomes and 62
      EST datasets. We found that the annotated genes in published genomes vary in
      coverage from 79% (Ciona intestinalis) to 99.8% (human) with an average of 92%,
      suggesting a value for the underlying error rate in genome annotation, and a
      strategy for identifying single copy orthologs in larger datasets. In contrast,
      the vast majority of EST datasets with no corresponding genome sequence available
      are largely under-sampled and probably do not accurately represent the actual
      genomic complement of the organisms from which they are derived.

PMID- 22144878
TI  - Multiscale modeling of red blood cell mechanics and blood flow in malaria.
AB  - Red blood cells (RBCs) infected by a Plasmodium parasite in malaria may lose
      their membrane deformability with a relative membrane stiffening more than ten
      fold in comparison with healthy RBCs leading to potential capillary occlusions.
      Moreover, infected RBCs are able to adhere to other healthy and parasitized cells
      and to the vascular endothelium resulting in a substantial disruption of normal
      blood circulation. In the present work, we simulate infected RBCs in malaria
      using a multiscale RBC model based on the dissipative particle dynamics method,
      coupling scales at the sub-cellular level with scales at the vessel size. Our
      objective is to conduct a full validation of the RBC model with a diverse set of
      experimental data, including temperature dependence, and to identify the
      limitations of this purely mechanistic model. The simulated elastic deformations
      of parasitized RBCs match those obtained in optical-tweezers experiments for
      different stages of intra-erythrocytic parasite development. The rheological
      properties of RBCs in malaria are compared with those obtained by optical
      magnetic twisting cytometry and by monitoring membrane fluctuations at room,
      physiological, and febrile temperatures. We also study the dynamics of infected
      RBCs in Poiseuille flow in comparison with healthy cells and present validated
      bulk viscosity predictions of malaria-infected blood for a wide range of
      parasitemia levels (percentage of infected RBCs with respect to the total number
      of cells in a unit volume).

PMID- 22144879
TI  - BeadArray expression analysis using bioconductor.
AB  - Illumina whole-genome expression BeadArrays are a popular choice in gene
      profiling studies. Aside from the vendor-provided software tools for analyzing
      BeadArray expression data (GenomeStudio/BeadStudio), there exists a comprehensive
      set of open-source analysis tools in the Bioconductor project, many of which have
      been tailored to exploit the unique properties of this platform. In this article,
      we explore a number of these software packages and demonstrate how to perform a
      complete analysis of BeadArray data in various formats. The key steps of
      importing data, performing quality assessments, preprocessing, and annotation in
      the common setting of assessing differential expression in designed experiments
      will be covered.

PMID- 22144881
TI  - Genomics and privacy: implications of the new reality of closed data for the
      field.
AB  - Open source and open data have been driving forces in bioinformatics in the past.
      However, privacy concerns may soon change the landscape, limiting future access
      to important data sets, including personal genomics data. Here we survey this
      situation in some detail, describing, in particular, how the large scale of the
      data from personal genomic sequencing makes it especially hard to share data,
      exacerbating the privacy problem. We also go over various aspects of genomic
      privacy: first, there is basic identifiability of subjects having their genome
      sequenced. However, even for individuals who have consented to be identified,
      there is the prospect of very detailed future characterization of their genotype,
      which, unanticipated at the time of their consent, may be more personal and
      invasive than the release of their medical records. We go over various
      computational strategies for dealing with the issue of genomic privacy. One can
      "slice" and reformat datasets to allow them to be partially shared while securing
      the most private variants. This is particularly applicable to functional genomics
      information, which can be largely processed without variant information. For
      handling the most private data there are a number of legal and technological
      approaches-for example, modifying the informed consent procedure to acknowledge
      that privacy cannot be guaranteed, and/or employing a secure cloud computing
      environment. Cloud computing in particular may allow access to the data in a more
      controlled fashion than the current practice of downloading and computing on
      large datasets. Furthermore, it may be particularly advantageous for small labs,
      given that the burden of many privacy issues falls disproportionately on them in
      comparison to large corporations and genome centers. Finally, we discuss how
      education of future genetics researchers will be important, with curriculums
      emphasizing privacy and data security. However, teaching personal genomics with
      identifiable subjects in the university setting will, in turn, create additional
      privacy issues and social conundrums.

PMID- 22144880
TI  - Computational mass spectrometry-based proteomics.

PMID- 22144882
TI  - Chemotaxis when bacteria remember: drift versus diffusion.
AB  - Escherichia coli (E. coli) bacteria govern their trajectories by switching
      between running and tumbling modes as a function of the nutrient concentration
      they experienced in the past. At short time one observes a drift of the bacterial
      population, while at long time one observes accumulation in high-nutrient
      regions. Recent work has viewed chemotaxis as a compromise between drift toward
      favorable regions and accumulation in favorable regions. A number of earlier
      studies assume that a bacterium resets its memory at tumbles - a fact not borne
      out by experiment - and make use of approximate coarse-grained descriptions.
      Here, we revisit the problem of chemotaxis without resorting to any memory
      resets. We find that when bacteria respond to the environment in a non-adaptive
      manner, chemotaxis is generally dominated by diffusion, whereas when bacteria
      respond in an adaptive manner, chemotaxis is dominated by a bias in the motion.
      In the adaptive case, favorable drift occurs together with favorable
      accumulation. We derive our results from detailed simulations and a variety of
      analytical arguments. In particular, we introduce a new coarse-grained
      description of chemotaxis as biased diffusion, and we discuss the way it departs
      from older coarse-grained descriptions.

PMID- 22144883
TI  - Modelling the spread of HIV immune escape mutants in a vaccinated population.
AB  - Because cytotoxic T-lymphocytes (CTLs) have been shown to play a role in
      controlling human immunodeficiency virus (HIV) infection and because CTL-based
      simian immunodeficiency virus (SIV) vaccines have proved effective in non-human
      primates, one goal of HIV vaccine design is to elicit effective CTL responses in
      humans. Such a vaccine could improve viral control in patients who later become
      infected, thereby reducing onwards transmission and enhancing life expectancy in
      the absence of treatment. The ability of HIV to evolve mutations that evade CTLs
      and the ability of these 'escape mutants' to spread amongst the population poses
      a challenge to the development of an effective and robust vaccine. We present a
      mathematical model of within-host evolution and between-host transmission of CTL
      escape mutants amongst a population receiving a vaccine that elicits CTL
      responses to multiple epitopes. Within-host evolution at each epitope is
      represented by the outgrowth of escape mutants in hosts who restrict the epitope
      and their reversion in hosts who do not restrict the epitope. We use this model
      to investigate how the evolution and spread of escape mutants could affect the
      impact of a vaccine. We show that in the absence of escape, such a vaccine could
      markedly reduce the prevalence of both infection and disease in the population.
      However the impact of such a vaccine could be significantly abated by CTL escape
      mutants, especially if their selection in hosts who restrict the epitope is rapid
      and their reversion in hosts who do not restrict the epitope is slow. We also use
      the model to address whether a vaccine should span a broad or narrow range of CTL
      epitopes and target epitopes restricted by rare or common HLA types. We discuss
      the implications and limitations of our findings.

PMID- 22144884
TI  - Dynamics of mutant cells in hierarchical organized tissues.
AB  - Most tissues in multicellular organisms are maintained by continuous cell renewal
      processes. However, high turnover of many cells implies a large number of error
      prone cell divisions. Hierarchical organized tissue structures with stem cell
      driven cell differentiation provide one way to prevent the accumulation of
      mutations, because only few stem cells are long lived. We investigate the
      deterministic dynamics of cells in such a hierarchical multi compartment model,
      where each compartment represents a certain stage of cell differentiation. The
      dynamics of the interacting system is described by ordinary differential
      equations coupled across compartments. We present analytical solutions for these
      equations, calculate the corresponding extinction times and compare our results
      to individual based stochastic simulations. Our general compartment structure can
      be applied to different tissues, as for example hematopoiesis, the epidermis, or
      colonic crypts. The solutions provide a description of the average time
      development of stem cell and non stem cell driven mutants and can be used to
      illustrate general and specific features of the dynamics of mutant cells in such
      hierarchically structured populations. We illustrate one possible application of
      this approach by discussing the origin and dynamics of PIG-A mutant clones that
      are found in the bloodstream of virtually every healthy adult human. From this it
      is apparent, that not only the occurrence of a mutant but also the compartment of
      origin is of importance.

PMID- 22144885
TI  - Estimated comparative integration hotspots identify different behaviors of
      retroviral gene transfer vectors.
AB  - Integration of retroviral vectors in the human genome follows non random patterns
      that favor insertional deregulation of gene expression and may cause risks of
      insertional mutagenesis when used in clinical gene therapy. Understanding how
      viral vectors integrate into the human genome is a key issue in predicting these
      risks. We provide a new statistical method to compare retroviral integration
      patterns. We identified the positions where vectors derived from the Human
      Immunodeficiency Virus (HIV) and the Moloney Murine Leukemia Virus (MLV) show
      different integration behaviors in human hematopoietic progenitor cells. Non
      parametric density estimation was used to identify candidate comparative
      hotspots, which were then tested and ranked. We found 100 significative
      comparative hotspots, distributed throughout the chromosomes. HIV hotspots were
      wider and contained more genes than MLV ones. A Gene Ontology analysis of HIV
      targets showed enrichment of genes involved in antigen processing and
      presentation, reflecting the high HIV integration frequency observed at the MHC
      locus on chromosome 6. Four histone modifications/variants had a different mean
      density in comparative hotspots (H2AZ, H3K4me1, H3K4me3, H3K9me1), while gene
      expression within the comparative hotspots did not differ from background. These
      findings suggest the existence of epigenetic or nuclear three-dimensional
      topology contexts guiding retroviral integration to specific chromosome areas.

PMID- 22144886
TI  - Nutritional immunology: a multi-dimensional approach.

PMID- 22144887
TI  - Feeding cells induced by phytoparasitic nematodes require gamma-tubulin ring
      complex for microtubule reorganization.
AB  - Reorganization of the microtubule network is important for the fast isodiametric
      expansion of giant-feeding cells induced by root-knot nematodes. The efficiency
      of microtubule reorganization depends on the nucleation of new microtubules,
      their elongation rate and activity of microtubule severing factors. New
      microtubules in plants are nucleated by cytoplasmic or microtubule-bound gamma
      tubulin ring complexes. Here we investigate the requirement of gamma-tubulin
      complexes for giant feeding cells development using the interaction between
      Arabidopsis and Meloidogyne spp. as a model system. Immunocytochemical analyses
      demonstrate that gamma-tubulin localizes to both cortical cytoplasm and mitotic
      microtubule arrays of the giant cells where it can associate with microtubules.
      The transcripts of two Arabidopsis gamma-tubulin (TUBG1 and TUBG2) and two gamma
      tubulin complex proteins genes (GCP3 and GCP4) are upregulated in galls. Electron
      microscopy demonstrates association of GCP3 and gamma-tubulin as part of a
      complex in the cytoplasm of giant cells. Knockout of either or both gamma-tubulin
      genes results in the gene dose-dependent alteration of the morphology of feeding
      site and failure of nematode life cycle completion. We conclude that the gamma
      tubulin complex is essential for the control of microtubular network remodelling
      in the course of initiation and development of giant-feeding cells, and for the
      successful reproduction of nematodes in their plant hosts.

PMID- 22144888
TI  - Neonatal CD8 T-cell hierarchy is distinct from adults and is influenced by
      intrinsic T cell properties in respiratory syncytial virus infected mice.
AB  - Following respiratory syncytial virus infection of adult CB6F1 hybrid mice, a
      predictable CD8+ T cell epitope hierarchy is established with a strongly dominant
      response to a K(d)-restricted peptide (SYIGSINNI) from the M2 protein. The
      response to K(d)M2(82-90) is ~5-fold higher than the response to a subdominant
      epitope from the M protein (NAITNAKII, D(b)M(187-195)). After infection of
      neonatal mice, a distinctly different epitope hierarchy emerges with codominant
      responses to K(d)M2(82-90) and D(b)M(187-195). Adoptive transfer of naive CD8+ T
      cells from adults into congenic neonates prior to infection indicates that
      intrinsic CD8+ T cell factors contribute to age-related differences in hierarchy.
      Epitope-specific precursor frequency differs between adults and neonates and
      influences, but does not predict the hierarchy following infection. Additionally,
      dominance of K(d)M2(82-90)-specific cells does not correlate with TdT activity.
      Epitope-specific Vbeta repertoire usage is more restricted and functional avidity
      is lower in neonatal mice. The neonatal pattern of codominance changes after
      infection at 10 days of age, and rapidly shifts to the adult pattern of extreme
      K(d)M2(82-90)-dominance. Thus, the functional properties of T cells are
      selectively modified by developmental factors in an epitope-specific and age
      dependent manner.

PMID- 22144889
TI  - Two novel transcriptional regulators are essential for infection-related
      morphogenesis and pathogenicity of the rice blast fungus Magnaporthe oryzae.
AB  - The cyclic AMP-dependent protein kinase A signaling pathway plays a major role in
      regulating plant infection by the rice blast fungus Magnaporthe oryzae. Here, we
      report the identification of two novel genes, MoSOM1 and MoCDTF1, which were
      discovered in an insertional mutagenesis screen for non-pathogenic mutants of M.
      oryzae. MoSOM1 or MoCDTF1 are both necessary for development of spores and
      appressoria by M. oryzae and play roles in cell wall differentiation, regulating
      melanin pigmentation and cell surface hydrophobicity during spore formation.
      MoSom1 strongly interacts with MoStu1 (Mstu1), an APSES transcription factor
      protein, and with MoCdtf1, while also interacting more weakly with the catalytic
      subunit of protein kinase A (CpkA) in yeast two hybrid assays. Furthermore, the
      expression levels of MoSOM1 and MoCDTF1 were significantly reduced in both
      Deltamac1 and DeltacpkA mutants, consistent with regulation by the cAMP/PKA
      signaling pathway. MoSom1-GFP and MoCdtf1-GFP fusion proteins localized to the
      nucleus of fungal cells. Site-directed mutagenesis confirmed that nuclear
      localization signal sequences in MoSom1 and MoCdtf1 are essential for their sub
      cellular localization and biological functions. Transcriptional profiling
      revealed major changes in gene expression associated with loss of MoSOM1 during
      infection-related development. We conclude that MoSom1 and MoCdtf1 functions
      downstream of the cAMP/PKA signaling pathway and are novel transcriptional
      regulators associated with cellular differentiation during plant infection by the
      rice blast fungus.

PMID- 22144890
TI  - Longevity and composition of cellular immune responses following experimental
      Plasmodium falciparum malaria infection in humans.
AB  - Cellular responses to Plasmodium falciparum parasites, in particular interferon
      gamma (IFNgamma) production, play an important role in anti-malarial immunity.
      However, clinical immunity to malaria develops slowly amongst naturally exposed
      populations, the dynamics of cellular responses in relation to exposure are
      difficult to study and data about the persistence of such responses are
      controversial. Here we assess the longevity and composition of cellular immune
      responses following experimental malaria infection in human volunteers. We
      conducted a longitudinal study of cellular immunological responses to sporozoites
      (PfSpz) and asexual blood-stage (PfRBC) malaria parasites in naive human
      volunteers undergoing single (n = 5) or multiple (n = 10) experimental P.
      falciparum infections under highly controlled conditions. IFNgamma and
      interleukin-2 (IL-2) responses following in vitro re-stimulation were measured by
      flow-cytometry prior to, during and more than one year post infection. We show
      that cellular responses to both PfSpz and PfRBC are induced and remain almost
      undiminished up to 14 months after even a single malaria episode. Remarkably, not
      only 'adaptive' but also 'innate' lymphocyte subsets contribute to the increased
      IFNgamma response, including alphabetaT cells, gammadeltaT cells and NK cells.
      Furthermore, results from depletion and autologous recombination experiments of
      lymphocyte subsets suggest that immunological memory for PfRBC is carried within
      both the alphabetaT cells and gammadeltaT compartments. Indeed, the majority of
      cytokine producing T lymphocytes express an CD45RO(+) CD62L(-) effector memory
      (EM) phenotype both early and late post infection. Finally, we demonstrate that
      malaria infection induces and maintains polyfunctional (IFNgamma(+)IL-2(+)) EM
      responses against both PfRBC and PfSpz, previously found to be associated with
      protection. These data demonstrate that cellular responses can be readily induced
      and are long-lived following infection with P. falciparum, with a persisting
      contribution by not only adaptive but also (semi-)innate lymphocyte subsets. The
      implications hereof are positive for malaria vaccine development, but focus
      attention on those factors potentially inhibiting such responses in the field.

PMID- 22144891
TI  - Chikungunya virus neutralization antigens and direct cell-to-cell transmission
      are revealed by human antibody-escape mutants.
AB  - Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics
      throughout Africa and Asia, causing infectious arthritis and reportedly linked
      with fatal infections in newborns and elderly. Previous studies in animal models
      indicate that humoral immunity can protect against CHIKV infection, but despite
      the potential efficacy of B-cell-driven intervention strategies, there are no
      virus-specific vaccines or therapies currently available. In addition, CHIKV has
      been reported to elicit long-lasting virus-specific IgM in humans, and to
      establish long-term persistence in non-human primates, suggesting that the virus
      might evade immune defenses to establish chronic infections in man. However, the
      mechanisms of immune evasion potentially employed by CHIKV remain
      uncharacterized. We previously described two human monoclonal antibodies that
      potently neutralize CHIKV infection. In the current report, we have characterized
      CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV
      E2 domain B and fusion loop "groove" as the primary determinants of CHIKV
      interaction with these antibodies. Furthermore, for the first time, we have also
      demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves
      the E2 domain A and that is associated with viral resistance to antibody
      dependent neutralization. Identification of CHIKV sub-domains that are associated
      with human protective immunity, will pave the way for the development of CHIKV
      specific sub-domain vaccination strategies. Moreover, the clear demonstration of
      CHIKV cell-to-cell transmission and its possible role in the establishment of
      CHIKV persistence, will also inform the development of future anti-viral
      interventions. These data shed new light on CHIKV-host interactions that will
      help to combat human CHIKV infection and inform future studies of CHIKV
      pathogenesis.

PMID- 22144892
TI  - A systematic screen to discover and analyze apicoplast proteins identifies a
      conserved and essential protein import factor.
AB  - Parasites of the phylum Apicomplexa cause diseases that impact global health and
      economy. These unicellular eukaryotes possess a relict plastid, the apicoplast,
      which is an essential organelle and a validated drug target. However, much of its
      biology remains poorly understood, in particular its elaborate
      compartmentalization: four membranes defining four different spaces. Only a small
      number of organellar proteins have been identified in particular few proteins are
      known for non-luminal apicoplast compartments. We hypothesized that enlarging the
      catalogue of apicoplast proteins will contribute toward identifying new
      organellar functions and expand the realm of targets beyond a limited set of
      characterized pathways. We developed a bioinformatic screen based on mRNA
      abundance over the cell cycle and on phyletic distribution. We experimentally
      assessed 57 genes, and of 30 successful epitope tagged candidates eleven novel
      apicoplast proteins were identified. Of those, seven appear to target to the
      lumen of the organelle, and four localize to peripheral compartments. To address
      their function we then developed a robust system for the construction of
      conditional mutants via a promoter replacement strategy. We confirm the
      feasibility of this system by establishing conditional mutants for two selected
      genes--a luminal and a peripheral apicoplast protein. The latter is particularly
      intriguing as it encodes a hypothetical protein that is conserved in and unique
      to Apicomplexan parasites and other related organisms that maintain a red algal
      endosymbiont. Our studies suggest that this peripheral plastid protein, PPP1, is
      likely localized to the periplastid compartment. Conditional disruption of PPP1
      demonstrated that it is essential for parasite survival. Phenotypic analysis of
      this mutant is consistent with a role of the PPP1 protein in apicoplast
      biogenesis, specifically in import of nuclear-encoded proteins into the
      organelle.

PMID- 22144893
TI  - Acquisition of pneumococci specific effector and regulatory Cd4+ T cells
      localising within human upper respiratory-tract mucosal lymphoid tissue.
AB  - The upper respiratory tract mucosa is the location for commensal Streptococcus
      (S.) pneumoniae colonization and therefore represents a major site of contact
      between host and bacteria. The CD4(+) T cell response to pneumococcus is
      increasingly recognised as an important mediator of immunity that protects
      against invasive disease, with data suggesting a critical role for Th17 cells in
      mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate
      age-related sequestration of Th1 and Th17 CD4(+) T cells reactive to pneumococcal
      protein antigens within mucosal lymphoid tissue. CD25(hi) T cell depletion and
      utilisation of pneumococcal specific MHCII tetramers revealed the presence of
      antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to
      suppress these responses. The balance between mucosal effector and regulatory
      CD4(+) T cell immunity is likely to be critical to pneumococcal commensalism and
      the prevention of unwanted pathology associated with carriage. However, if
      dysregulated, such responses may render the host more susceptible to invasive
      pneumococcal infection and adversely affect the successful implementation of both
      polysaccharide-conjugate and novel protein-based pneumococcal vaccines.

PMID- 22144894
TI  - Acid stability of the hemagglutinin protein regulates H5N1 influenza virus
      pathogenicity.
AB  - Highly pathogenic avian influenza viruses of the H5N1 subtype continue to
      threaten agriculture and human health. Here, we use biochemistry and x-ray
      crystallography to reveal how amino-acid variations in the hemagglutinin (HA)
      protein contribute to the pathogenicity of H5N1 influenza virus in chickens. HA
      proteins from highly pathogenic (HP) A/chicken/Hong Kong/YU562/2001 and
      moderately pathogenic (MP) A/goose/Hong Kong/437-10/1999 isolates of H5N1 were
      found to be expressed and cleaved in similar amounts, and both proteins had
      similar receptor-binding properties. However, amino-acid variations at positions
      104 and 115 in the vestigial esterase sub-domain of the HA1 receptor-binding
      domain (RBD) were found to modulate the pH of HA activation such that the HP and
      MP HA proteins are activated for membrane fusion at pH 5.7 and 5.3, respectively.
      In general, an increase in H5N1 pathogenicity in chickens was found to correlate
      with an increase in the pH of HA activation for mutant and chimeric HA proteins
      in the observed range of pH 5.2 to 6.0. We determined a crystal structure of the
      MP HA protein at 2.50 A resolution and two structures of HP HA at 2.95 and 3.10 A
      resolution. Residues 104 and 115 that modulate the acid stability of the HA
      protein are situated at the N- and C-termini of the 110-helix in the vestigial
      esterase sub-domain, which interacts with the B loop of the HA2 stalk domain.
      Interactions between the 110-helix and the stalk domain appear to be important in
      regulating HA protein acid stability, which in turn modulates influenza virus
      replication and pathogenesis. Overall, an optimal activation pH of the HA protein
      is found to be necessary for high pathogenicity by H5N1 influenza virus in avian
      species.

PMID- 22144895
TI  - Follicular dendritic cell-specific prion protein (PrP) expression alone is
      sufficient to sustain prion infection in the spleen.
AB  - Prion diseases are characterised by the accumulation of PrP(Sc), an abnormally
      folded isoform of the cellular prion protein (PrP(C)), in affected tissues.
      Following peripheral exposure high levels of prion-specific PrP(Sc) accumulate
      first upon follicular dendritic cells (FDC) in lymphoid tissues before spreading
      to the CNS. Expression of PrP(C) is mandatory for cells to sustain prion
      infection and FDC appear to express high levels. However, whether FDC actively
      replicate prions or simply acquire them from other infected cells is uncertain.
      In the attempts to-date to establish the role of FDC in prion pathogenesis it was
      not possible to dissociate the Prnp expression of FDC from that of the nervous
      system and all other non-haematopoietic lineages. This is important as FDC may
      simply acquire prions after synthesis by other infected cells. To establish the
      role of FDC in prion pathogenesis transgenic mice were created in which PrP(C)
      expression was specifically "switched on" or "off" only on FDC. We show that
      PrP(C)-expression only on FDC is sufficient to sustain prion replication in the
      spleen. Furthermore, prion replication is blocked in the spleen when PrP(C)
      expression is specifically ablated only on FDC. These data definitively
      demonstrate that FDC are the essential sites of prion replication in lymphoid
      tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion
      accumulation without apparent consequences for FDC status represents a novel
      opportunity to prevent neuroinvasion by modulation of PrP(C) expression on FDC.

PMID- 22144896
TI  - Late repression of NF-kappaB activity by invasive but not non-invasive
      meningococcal isolates is required to display apoptosis of epithelial cells.
AB  - Meningococcal invasive isolates of the ST-11 clonal complex are most frequently
      associated with disease and rarely found in carriers. Unlike carriage isolates,
      invasive isolates induce apoptosis in epithelial cells through the TNF-alpha
      signaling pathway. While invasive and non-invasive isolates are both able to
      trigger the TLR4/MyD88 pathway in lipooligosaccharide (LOS)-dependant manner, we
      show that only non-invasive isolates were able to induce sustained NF-kappaB
      activity in infected epithelial cells. ST-11 invasive isolates initially
      triggered a strong NF-kappaB activity in infected epithelial cells that was
      abolished after 9 h of infection and was associated with sustained activation of
      JNK, increased levels of membrane TNFR1, and induction of apoptosis. In contrast,
      infection with carriage isolates lead to prolonged activation of NF-kappaB that
      was associated with a transient activation of JNK increased TACE/ADAM17-mediated
      shedding of TNFR1 and protection against apoptosis. Our data provide insights to
      understand the meningococcal duality between invasiveness and asymptomatic
      carriage.

PMID- 22144897
TI  - A temporal role of type I interferon signaling in CD8+ T cell maturation during
      acute West Nile virus infection.
AB  - A genetic absence of the common IFN-alpha/beta signaling receptor (IFNAR) in mice
      is associated with enhanced viral replication and altered adaptive immune
      responses. However, analysis of IFNAR(-/-) mice is limited for studying the
      functions of type I IFN at discrete stages of viral infection. To define the
      temporal functions of type I IFN signaling in the context of infection by West
      Nile virus (WNV), we treated mice with MAR1-5A3, a neutralizing, non cell
      depleting anti-IFNAR antibody. Inhibition of type I IFN signaling at or before
      day 2 after infection was associated with markedly enhanced viral burden, whereas
      treatment at day 4 had substantially less effect on WNV dissemination. While
      antibody treatment prior to infection resulted in massive expansion of virus
      specific CD8(+) T cells, blockade of type I IFN signaling starting at day 4
      induced dysfunctional CD8(+) T cells with depressed cytokine responses and
      expression of phenotypic markers suggesting exhaustion. Thus, only the later
      maturation phase of anti-WNV CD8(+) T cell development requires type I IFN
      signaling. WNV infection experiments in BATF3(-/-) mice, which lack CD8-alpha
      dendritic cells and have impaired priming due to inefficient antigen cross
      presentation, revealed a similar effect of blocking IFN signaling on CD8(+) T
      cell maturation. Collectively, our results suggest that cell non-autonomous type
      I IFN signaling shapes maturation of antiviral CD8(+) T cell response at a stage
      distinct from the initial priming event.

PMID- 22144898
TI  - Computational and biochemical analysis of the Xanthomonas effector AvrBs2 and its
      role in the modulation of Xanthomonas type three effector delivery.
AB  - Effectors of the bacterial type III secretion system provide invaluable molecular
      probes to elucidate the molecular mechanisms of plant immunity and pathogen
      virulence. In this report, we focus on the AvrBs2 effector protein from the
      bacterial pathogen Xanthomonas euvesicatoria (Xe), the causal agent of bacterial
      spot disease of tomato and pepper. Employing homology-based structural analysis,
      we generate a three-dimensional structural model for the AvrBs2 protein and
      identify catalytic sites in its putative glycerolphosphodiesterase domain (GDE).
      We demonstrate that the identified catalytic region of AvrBs2 was able to
      functionally replace the GDE catalytic site of the bacterial
      glycerophosphodiesterase BhGlpQ cloned from Borrelia hermsii and is required for
      AvrBs2 virulence. Mutations in the GDE catalytic domain did not disrupt the
      recognition of AvrBs2 by the cognate plant resistance gene Bs2. In addition,
      AvrBs2 activation of Bs2 suppressed subsequent delivery of other Xanthomonas type
      III effectors into the host plant cells. Investigation of the mechanism
      underlying this modulation of the type III secretion system may offer new
      strategies to generate broad-spectrum resistance to bacterial pathogens.

PMID- 22144899
TI  - The enteropathogenic E. coli (EPEC) Tir effector inhibits NF-kappaB activity by
      targeting TNFalpha receptor-associated factors.
AB  - Enteropathogenic Escherichia coli (EPEC) disease depends on the transfer of
      effector proteins into epithelia lining the human small intestine. EPEC E2348/69
      has at least 20 effector genes of which six are located with the effector
      delivery system genes on the Locus of Enterocyte Effacement (LEE) Pathogenicity
      Island. Our previous work implied that non-LEE-encoded (Nle) effectors possess
      functions that inhibit epithelial anti-microbial and inflammation-inducing
      responses by blocking NF-kappaB transcription factor activity. Indeed, screens by
      us and others have identified novel inhibitory mechanisms for NleC and NleH, with
      key co-operative functions for NleB1 and NleE1. Here, we demonstrate that the LEE
      encoded Translocated-intimin receptor (Tir) effector has a potent and specific
      ability to inhibit NF-kappaB activation. Indeed, biochemical, imaging and
      immunoprecipitation studies reveal a novel inhibitory mechanism whereby Tir
      interaction with cytoplasm-located TNFalpha receptor-associated factor (TRAF)
      adaptor proteins induces their proteasomal-independent degradation. Infection
      studies support this Tir-TRAF relationship but reveal that Tir, like NleC and
      NleH, has a non-essential contribution in EPEC's NF-kappaB inhibitory capacity
      linked to Tir's activity being suppressed by undefined EPEC factors. Infections
      in a disease-relevant intestinal model confirm key NF-kappaB inhibitory roles for
      the NleB1/NleE1 effectors, with other studies providing insights on host targets.
      The work not only reveals a second Intimin-independent property for Tir and a
      novel EPEC effector-mediated NF-kappaB inhibitory mechanism but also lends itself
      to speculations on the evolution of EPEC's capacity to inhibit NF-kappaB
      function.

PMID- 22144900
TI  - Autophagy protein Atg3 is essential for maintaining mitochondrial integrity and
      for normal intracellular development of Toxoplasma gondii tachyzoites.
AB  - Autophagy is a cellular process that is highly conserved among eukaryotes and
      permits the degradation of cellular material. Autophagy is involved in multiple
      survival-promoting processes. It not only facilitates the maintenance of cell
      homeostasis by degrading long-lived proteins and damaged organelles, but it also
      plays a role in cell differentiation and cell development. Equally important is
      its function for survival in stress-related conditions such as recycling of
      proteins and organelles during nutrient starvation. Protozoan parasites have
      complex life cycles and face dramatically changing environmental conditions;
      whether autophagy represents a critical coping mechanism throughout these changes
      remains poorly documented. To investigate this in Toxoplasma gondii, we have used
      TgAtg8 as an autophagosome marker and showed that autophagy and the associated
      cellular machinery are present and functional in the parasite. In extracellular
      T. gondii tachyzoites, autophagosomes were induced in response to amino acid
      starvation, but they could also be observed in culture during the normal
      intracellular development of the parasites. Moreover, we generated a conditional
      T. gondii mutant lacking the orthologue of Atg3, a key autophagy protein. TgAtg3
      depleted parasites were unable to regulate the conjugation of TgAtg8 to the
      autophagosomal membrane. The mutant parasites also exhibited a pronounced
      fragmentation of their mitochondrion and a drastic growth phenotype. Overall, our
      results show that TgAtg3-dependent autophagy might be regulating mitochondrial
      homeostasis during cell division and is essential for the normal development of
      T. gondii tachyzoites.

PMID- 22144901
TI  - Genesis of mammalian prions: from non-infectious amyloid fibrils to a
      transmissible prion disease.
AB  - The transmissible agent of prion disease consists of a prion protein in its
      abnormal, beta-sheet rich state (PrP(Sc)), which is capable of replicating itself
      according to the template-assisted mechanism. This mechanism postulates that the
      folding pattern of a newly recruited polypeptide chain accurately reproduces that
      of a PrP(Sc) template. Here we report that authentic PrP(Sc) and transmissible
      prion disease can be generated de novo in wild type animals by recombinant PrP
      (rPrP) amyloid fibrils, which are structurally different from PrP(Sc) and lack
      any detectable PrP(Sc) particles. When induced by rPrP fibrils, a long silent
      stage that involved two serial passages preceded development of the clinical
      disease. Once emerged, the prion disease was characterized by unique clinical,
      neuropathological, and biochemical features. The long silent stage to the disease
      was accompanied by significant transformation in neuropathological properties and
      biochemical features of the proteinase K-resistant PrP material (PrPres) before
      authentic PrP(Sc) evolved. The current work illustrates that transmissible prion
      diseases can be induced by PrP structures different from that of authentic
      PrP(Sc) and suggests that a new mechanism different from the classical templating
      exists. This new mechanism designated as "deformed templating" postulates that a
      change in the PrP folding pattern from the one present in rPrP fibrils to an
      alternative specific for PrP(Sc) can occur. The current work provides important
      new insight into the mechanisms underlying genesis of the transmissible protein
      states and has numerous implications for understanding the etiology of
      neurodegenerative diseases.

PMID- 22144902
TI  - Polar flagellar biosynthesis and a regulator of flagellar number influence
      spatial parameters of cell division in Campylobacter jejuni.
AB  - Spatial and numerical regulation of flagellar biosynthesis results in different
      flagellation patterns specific for each bacterial species. Campylobacter jejuni
      produces amphitrichous (bipolar) flagella to result in a single flagellum at both
      poles. These flagella confer swimming motility and a distinctive darting motility
      necessary for infection of humans to cause diarrheal disease and animals to
      promote commensalism. In addition to flagellation, symmetrical cell division is
      spatially regulated so that the divisome forms near the cellular midpoint. We
      have identified an unprecedented system for spatially regulating cell division in
      C. jejuni composed by FlhG, a regulator of flagellar number in polar flagellates,
      and components of amphitrichous flagella. Similar to its role in other polarly
      flagellated bacteria, we found that FlhG regulates flagellar biosynthesis to
      limit poles of C. jejuni to one flagellum. Furthermore, we discovered that FlhG
      negatively influences the ability of FtsZ to initiate cell division. Through
      analysis of specific flagellar mutants, we discovered that components of the
      motor and switch complex of amphitrichous flagella are required with FlhG to
      specifically inhibit division at poles. Without FlhG or specific motor and switch
      complex proteins, cell division occurs more often at polar regions to form
      minicells. Our findings suggest a new understanding for the biological
      requirement of the amphitrichous flagellation pattern in bacteria that extend
      beyond motility, virulence, and colonization. We propose that amphitrichous
      bacteria such as Campylobacter species advantageously exploit placement of
      flagella at both poles to spatially regulate an FlhG-dependent mechanism to
      inhibit polar cell division, thereby encouraging symmetrical cell division to
      generate the greatest number of viable offspring. Furthermore, we found that
      other polarly-flagellated bacteria produce FlhG proteins that influence cell
      division, suggesting that FlhG and polar flagella may function together in a
      broad range of bacteria to spatially regulate division.

PMID- 22144903
TI  - Wall teichoic acids of Staphylococcus aureus limit recognition by the drosophila
      peptidoglycan recognition protein-SA to promote pathogenicity.
AB  - The cell wall of gram-positive bacteria is a complex network of surface proteins,
      capsular polysaccharides and wall teichoic acids (WTA) covalently linked to
      Peptidoglycan (PG). The absence of WTA has been associated with a reduced
      pathogenicity of Staphylococcus aureus (S. aureus). Here, we assessed whether
      this was due to increased detection of PG, an important target of innate immune
      receptors. Antibiotic-mediated or genetic inhibition of WTA production in S.
      aureus led to increased binding of the non-lytic PG Recognition Protein-SA (PGRP
      SA), and this was associated with a reduction in host susceptibility to
      infection. Moreover, PGRP-SD, another innate sensor required to control wild type
      S. aureus infection, became redundant. Our data imply that by using WTA to limit
      access of innate immune receptors to PG, under-detected bacteria are able to
      establish an infection and ultimately overwhelm the host. We propose that
      different PGRPs work in concert to counter this strategy.

PMID- 22144905
TI  - SREBP coordinates iron and ergosterol homeostasis to mediate triazole drug and
      hypoxia responses in the human fungal pathogen Aspergillus fumigatus.
AB  - Sterol regulatory element binding proteins (SREBPs) are a class of basic helix
      loop-helix transcription factors that regulate diverse cellular responses in
      eukaryotes. Adding to the recognized importance of SREBPs in human health, SREBPs
      in the human fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus
      are required for fungal virulence and susceptibility to triazole antifungal
      drugs. To date, the exact mechanism(s) behind the role of SREBP in these observed
      phenotypes is not clear. Here, we report that A. fumigatus SREBP, SrbA, mediates
      regulation of iron acquisition in response to hypoxia and low iron conditions. To
      further define SrbA's role in iron acquisition in relation to previously studied
      fungal regulators of iron metabolism, SreA and HapX, a series of mutants were
      generated in the DeltasrbA background. These data suggest that SrbA is activated
      independently of SreA and HapX in response to iron limitation, but that HapX mRNA
      induction is partially dependent on SrbA. Intriguingly, exogenous addition of
      high iron or genetic deletion of sreA in the DeltasrbA background was able to
      partially rescue the hypoxia growth, triazole drug susceptibility, and decrease
      in ergosterol content phenotypes of DeltasrbA. Thus, we conclude that the fungal
      SREBP, SrbA, is critical for coordinating genes involved in iron acquisition and
      ergosterol biosynthesis under hypoxia and low iron conditions found at sites of
      human fungal infections. These results support a role for SREBP-mediated iron
      regulation in fungal virulence, and they lay a foundation for further exploration
      of SREBP's role in iron homeostasis in other eukaryotes.

PMID- 22144904
TI  - Integrating genome-wide genetic variations and monocyte expression data reveals
      trans-regulated gene modules in humans.
AB  - One major expectation from the transcriptome in humans is to characterize the
      biological basis of associations identified by genome-wide association studies.
      So far, few cis expression quantitative trait loci (eQTLs) have been reliably
      related to disease susceptibility. Trans-regulating mechanisms may play a more
      prominent role in disease susceptibility. We analyzed 12,808 genes detected in at
      least 5% of circulating monocyte samples from a population-based sample of 1,490
      European unrelated subjects. We applied a method of extraction of expression
      patterns-independent component analysis-to identify sets of co-regulated genes.
      These patterns were then related to 675,350 SNPs to identify major trans-acting
      regulators. We detected three genomic regions significantly associated with co
      regulated gene modules. Association of these loci with multiple expression traits
      was replicated in Cardiogenics, an independent study in which expression profiles
      of monocytes were available in 758 subjects. The locus 12q13 (lead SNP
      rs11171739), previously identified as a type 1 diabetes locus, was associated
      with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of
      which (MADCAM1) is a potential candidate for mediating T1D susceptibility. The
      locus 12q24 (lead SNP rs653178), which has demonstrated extensive disease
      pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was
      associated to a pattern strongly correlating to blood pressure level. The
      strongest trans eQTL in this pattern was CRIP1, a known marker of cellular
      proliferation in cancer. The locus 12q15 (lead SNP rs11177644) was associated
      with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans
      eQTLs, several of them tumor-related genes. This study shows that a method
      exploiting the structure of co-expressions among genes can help identify genomic
      regions involved in trans regulation of sets of genes and can provide clues for
      understanding the mechanisms linking genome-wide association loci to disease.

PMID- 22144906
TI  - Hierarchical generalized linear models for multiple groups of rare and common
      variants: jointly estimating group and individual-variant effects.
AB  - Complex diseases and traits are likely influenced by many common and rare genetic
      variants and environmental factors. Detecting disease susceptibility variants is
      a challenging task, especially when their frequencies are low and/or their
      effects are small or moderate. We propose here a comprehensive hierarchical
      generalized linear model framework for simultaneously analyzing multiple groups
      of rare and common variants and relevant covariates. The proposed hierarchical
      generalized linear models introduce a group effect and a genetic score (i.e., a
      linear combination of main-effect predictors for genetic variants) for each group
      of variants, and jointly they estimate the group effects and the weights of the
      genetic scores. This framework includes various previous methods as special
      cases, and it can effectively deal with both risk and protective variants in a
      group and can simultaneously estimate the cumulative contribution of multiple
      variants and their relative importance. Our computational strategy is based on
      extending the standard procedure for fitting generalized linear models in the
      statistical software R to the proposed hierarchical models, leading to the
      development of stable and flexible tools. The methods are illustrated with
      sequence data in gene ANGPTL4 from the Dallas Heart Study. The performance of the
      proposed procedures is further assessed via simulation studies. The methods are
      implemented in a freely available R package BhGLM
      (http://www.ssg.uab.edu/bhglm/).

PMID- 22144907
TI  - Repetitive elements may comprise over two-thirds of the human genome.
AB  - Transposable elements (TEs) are conventionally identified in eukaryotic genomes
      by alignment to consensus element sequences. Using this approach, about half of
      the human genome has been previously identified as TEs and low-complexity
      repeats. We recently developed a highly sensitive alternative de novo strategy, P
      clouds, that instead searches for clusters of high-abundance oligonucleotides
      that are related in sequence space (oligo "clouds"). We show here that P-clouds
      predicts >840 Mbp of additional repetitive sequences in the human genome, thus
      suggesting that 66%-69% of the human genome is repetitive or repeat-derived. To
      investigate this remarkable difference, we conducted detailed analyses of the
      ability of both P-clouds and a commonly used conventional approach, RepeatMasker
      (RM), to detect different sized fragments of the highly abundant human Alu and
      MIR SINEs. RM can have surprisingly low sensitivity for even moderately long
      fragments, in contrast to P-clouds, which has good sensitivity down to small
      fragment sizes (~25 bp). Although short fragments have a high intrinsic
      probability of being false positives, we performed a probabilistic annotation
      that reflects this fact. We further developed "element-specific" P-clouds (ESPs)
      to identify novel Alu and MIR SINE elements, and using it we identified ~100 Mb
      of previously unannotated human elements. ESP estimates of new MIR sequences are
      in good agreement with RM-based predictions of the amount that RM missed. These
      results highlight the need for combined, probabilistic genome annotation
      approaches and suggest that the human genome consists of substantially more
      repetitive sequence than previously believed.

PMID- 22144908
TI  - Genome instability and transcription elongation impairment in human cells
      depleted of THO/TREX.
AB  - THO/TREX connects transcription with genome integrity in yeast, but a role of
      mammalian THO in these processes is uncertain, which suggests a differential
      implication of mRNP biogenesis factors in genome integrity in yeast and humans.
      We show that human THO depletion impairs transcription elongation and mRNA export
      and increases instability associated with DNA breaks, leading to hyper
      recombination and gammaH2AX and 53BP1 foci accumulation. This is accompanied by
      replication alteration as determined by DNA combing. Genome instability is R-loop
      dependent, as deduced from the ability of the AID enzyme to increase DNA damage
      and of RNaseH to reduce it, or from the enhancement of R-loop-dependent class
      switching caused by THOC1-depletion in CH12 murine cells. Therefore, mammalian
      THO prevents R-loop formation and has a role in genome dynamics and function
      consistent with an evolutionary conservation of the functional connection between
      these mRNP biogenesis factors and genome integrity that had not been anticipated.

PMID- 22144909
TI  - The fission yeast stress-responsive MAPK pathway promotes meiosis via the
      phosphorylation of Pol II CTD in response to environmental and feedback cues.
AB  - The RRM-type RNA-binding protein Mei2 is a master regulator of meiosis in fission
      yeast, in which it stabilizes meiosis-specific mRNAs by blocking their
      destruction. Artificial activation of Mei2 can provoke the entire meiotic
      process, and it is suspected that Mei2 may do more than the stabilization of
      meiosis-specific mRNAs. In our current study using a new screening system, we
      show that Mei2 genetically interacts with subunits of CTDK-I, which
      phosphorylates serine-2 residues on the C-terminal domain of RNA polymerase II
      (Pol II CTD). Phosphorylation of CTD Ser-2 is essential to enable the robust
      transcription of ste11, which encodes an HMG-type transcription factor that
      regulates the expression of mei2 and other genes necessary for sexual
      development. CTD Ser-2 phosphorylation increases under nitrogen starvation, and
      the stress-responsive MAP kinase pathway, mediated by Wis1 MAPKK and Sty1 MAPK,
      is critical for this stress response. Sty1 phosphorylates Lsk1, the catalytic
      subunit of CTDK-I. Furthermore, a feedback loop stemming from activated Mei2 to
      Win1 and Wis4 MAPKKKs operates in this pathway and eventually enhances CTD Ser-2
      phosphorylation and ste11 transcription. Hence, in addition to starting meiosis,
      Mei2 functions to reinforce the commitment to it, once cells have entered this
      process. This study also demonstrates clearly that the stress-responsive MAP
      kinase pathway can modulates gene expression through phosphorylation of Pol II
      CTD.

PMID- 22144910
TI  - Identification of a genomic reservoir for new TRIM genes in primate genomes.
AB  - Tripartite Motif (TRIM) ubiquitin ligases act in the innate immune response
      against viruses. One of the best characterized members of this family,
      TRIM5alpha, serves as a potent retroviral restriction factor with activity
      against HIV. Here, we characterize what are likely to be the youngest TRIM genes
      in the human genome. For instance, we have identified 11 TRIM genes that are
      specific to humans and African apes (chimpanzees, bonobos, and gorillas) and
      another 7 that are human-specific. Many of these young genes have never been
      described, and their identification brings the total number of known human TRIM
      genes to approximately 100. These genes were acquired through segmental
      duplications, most of which originated from a single locus on chromosome 11.
      Another polymorphic duplication of this locus has resulted in these genes being
      copy number variable within the human population, with a Han Chinese woman
      identified as having 12 additional copies of these TRIM genes compared to other
      individuals screened in this study. Recently, this locus was annotated as one of
      34 "hotspot" regions that are also copy number variable in the genomes of
      chimpanzees and rhesus macaques. Most of the young TRIM genes originating from
      this locus are expressed, spliced, and contain signatures of positive natural
      selection in regions known to determine virus recognition in TRIM5alpha. However,
      we find that they do not restrict the same retroviruses as TRIM5alpha, consistent
      with the high degree of divergence observed in the regions that control target
      specificity. We propose that this recombinationally volatile locus serves as a
      reservoir from which new TRIM genes arise through segmental duplication, allowing
      primates to continually acquire new antiviral genes that can be selected to
      target new and evolving pathogens.

PMID- 22144911
TI  - A population genetics-phylogenetics approach to inferring natural selection in
      coding sequences.
AB  - Through an analysis of polymorphism within and divergence between species, we can
      hope to learn about the distribution of selective effects of mutations in the
      genome, changes in the fitness landscape that occur over time, and the location
      of sites involved in key adaptations that distinguish modern-day species. We
      introduce a novel method for the analysis of variation in selection pressures
      within and between species, spatially along the genome and temporally between
      lineages. We model codon evolution explicitly using a joint population genetics
      phylogenetics approach that we developed for the construction of multiallelic
      models with mutation, selection, and drift. Our approach has the advantage of
      performing direct inference on coding sequences, inferring ancestral states
      probabilistically, utilizing allele frequency information, and generalizing to
      multiple species. We use a Bayesian sliding window model for intragenic variation
      in selection coefficients that efficiently combines information across sites and
      captures spatial clustering within the genome. To demonstrate the utility of the
      method, we infer selective pressures acting in Drosophila melanogaster and D.
      simulans from polymorphism and divergence data for 100 X-linked coding regions.

PMID- 22144912
TI  - Targeted proteolysis of plectin isoform 1a accounts for hemidesmosome dysfunction
      in mice mimicking the dominant skin blistering disease EBS-Ogna.
AB  - Autosomal recessive mutations in the cytolinker protein plectin account for the
      multisystem disorders epidermolysis bullosa simplex (EBS) associated with
      muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and congenital myasthenia
      (EBS-CMS). In contrast, a dominant missense mutation leads to the disease EBS
      Ogna, manifesting exclusively as skin fragility. We have exploited this trait to
      study the molecular basis of hemidesmosome failure in EBS-Ogna and to reveal the
      contribution of plectin to hemidesmosome homeostasis. We generated EBS-Ogna knock
      in mice mimicking the human phenotype and show that blistering reflects
      insufficient protein levels of the hemidesmosome-associated plectin isoform 1a.
      We found that plectin 1a, in contrast to plectin 1c, the major isoform expressed
      in epidermal keratinocytes, is proteolytically degraded, supporting the notion
      that degradation of hemidesmosome-anchored plectin is spatially controlled. Using
      recombinant proteins, we show that the mutation renders plectin's 190-nm-long
      coiled-coil rod domain more vulnerable to cleavage by calpains and other
      proteases activated in the epidermis but not in skeletal muscle. Accordingly,
      treatment of cultured EBS-Ogna keratinocytes as well as of EBS-Ogna mouse skin
      with calpain inhibitors resulted in increased plectin 1a protein expression
      levels. Moreover, we report that plectin's rod domain forms dimeric structures
      that can further associate laterally into remarkably stable (paracrystalline)
      polymers. We propose focal self-association of plectin molecules as a novel
      mechanism contributing to hemidesmosome homeostasis and stabilization.

PMID- 22144913
TI  - Widespread cotranslational formation of protein complexes.
AB  - Most cellular processes are conducted by multi-protein complexes. However, little
      is known about how these complexes are assembled. In particular, it is not known
      if they are formed while one or more members of the complexes are being
      translated (cotranslational assembly). We took a genomic approach to address this
      question, by systematically identifying mRNAs associated with specific proteins.
      In a sample of 31 proteins from Schizosaccharomyces pombe that did not contain
      RNA-binding domains, we found that ~38% copurify with mRNAs that encode
      interacting proteins. For example, the cyclin-dependent kinase Cdc2p associates
      with the rum1 and cdc18 mRNAs, which encode, respectively, an inhibitor of Cdc2p
      kinase activity and an essential regulator of DNA replication. Both proteins
      interact with Cdc2p and are key cell cycle regulators. We obtained analogous
      results with proteins with different structures and cellular functions (kinesins,
      protein kinases, transcription factors, proteasome components, etc.). We showed
      that copurification of a bait protein and of specific mRNAs was dependent on the
      presence of the proteins encoded by the interacting mRNAs and on polysomal
      integrity. These results indicate that these observed associations reflect the
      cotranslational interaction between the bait and the nascent proteins encoded by
      the interacting mRNAs. Therefore, we show that the cotranslational formation of
      protein-protein interactions is a widespread phenomenon.

PMID- 22144914
TI  - Charcot-Marie-Tooth-linked mutant GARS is toxic to peripheral neurons independent
      of wild-type GARS levels.
AB  - Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral
      neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene
      (GARS). In addition to GARS, mutations in three other tRNA synthetase genes cause
      similar neuropathies, although the underlying mechanisms are not fully
      understood. To address this, we generated transgenic mice that ubiquitously over
      express wild-type GARS and crossed them to two dominant mouse models of CMT2D to
      distinguish loss-of-function and gain-of-function mechanisms. Over-expression of
      wild-type GARS does not improve the neuropathy phenotype in heterozygous Gars
      mutant mice, as determined by histological, functional, and behavioral tests.
      Transgenic GARS is able to rescue a pathological point mutation as a homozygote
      or in complementation tests with a Gars null allele, demonstrating the
      functionality of the transgene and revealing a recessive loss-of-function
      component of the point mutation. Missense mutations as transgene-rescued
      homozygotes or compound heterozygotes have a more severe neuropathy than
      heterozygotes, indicating that increased dosage of the disease-causing alleles
      results in a more severe neurological phenotype, even in the presence of a wild
      type transgene. We conclude that, although missense mutations of Gars may cause
      some loss of function, the dominant neuropathy phenotype observed in mice is
      caused by a dose-dependent gain of function that is not mitigated by over
      expression of functional wild-type protein.

PMID- 22144915
TI  - Genome-wide meta-analysis of five Asian cohorts identifies PDGFRA as a
      susceptibility locus for corneal astigmatism.
AB  - Corneal astigmatism refers to refractive abnormalities and irregularities in the
      curvature of the cornea, and this interferes with light being accurately focused
      at a single point in the eye. This ametropic condition is highly prevalent,
      influences visual acuity, and is a highly heritable trait. There is currently a
      paucity of research in the genetic etiology of corneal astigmatism. Here we
      report the results from five genome-wide association studies of corneal
      astigmatism across three Asian populations, with an initial discovery set of
      4,254 Chinese and Malay individuals consisting of 2,249 cases and 2,005 controls.
      Replication was obtained from three surveys comprising of 2,139 Indians, an
      additional 929 Chinese children, and an independent 397 Chinese family trios.
      Variants in PDGFRA on chromosome 4q12 (lead SNP: rs7677751, allelic odds ratio =
      1.26 (95% CI: 1.16-1.36), P(meta) = 7.87*10(-9)) were identified to be
      significantly associated with corneal astigmatism, exhibiting consistent effect
      sizes across all five cohorts. This highlights the potential role of variants in
      PDGFRA in the genetic etiology of corneal astigmatism across diverse Asian
      populations.

PMID- 22144916
TI  - The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to
      differentiate.
AB  - Homeostasis of most adult tissues is maintained by balancing stem cell self
      renewal and differentiation, but whether post-transcriptional mechanisms can
      regulate this process is unknown. Here, we identify that an RNA methyltransferase
      (Misu/Nsun2) is required to balance stem cell self-renewal and differentiation in
      skin. In the epidermis, this methyltransferase is found in a defined sub
      population of hair follicle stem cells poised to undergo lineage commitment, and
      its depletion results in enhanced quiescence and aberrant stem cell
      differentiation. Our results reveal that post-transcriptional RNA methylation can
      play a previously unappreciated role in controlling stem cell fate.

PMID- 22144917
TI  - The major roles of DNA polymerases epsilon and delta at the eukaryotic
      replication fork are evolutionarily conserved.
AB  - Coordinated replication of eukaryotic genomes is intrinsically asymmetric, with
      continuous leading strand synthesis preceding discontinuous lagging strand
      synthesis. Here we provide two types of evidence indicating that, in fission
      yeast, these two biosynthetic tasks are performed by two different replicases.
      First, in Schizosaccharomyces pombe strains encoding a poldelta-L591M mutator
      allele, base substitutions in reporter genes placed in opposite orientations
      relative to a well-characterized replication origin are strand-specific and
      distributed in patterns implying that Poldelta is primarily involved in lagging
      strand replication. Second, in strains encoding a polepsilon-M630F allele and
      lacking the ability to repair rNMPs in DNA due to a defect in RNase H2, rNMPs are
      selectively observed in nascent leading strand DNA. The latter observation
      demonstrates that abundant rNMP incorporation during replication can be tolerated
      and that they are normally removed in an RNase H2-dependent manner. This provides
      strong physical evidence that Polepsilon is the primary leading strand replicase.
      Collectively, these data and earlier results in budding yeast indicate that the
      major roles of Poldelta and Polepsilon at the eukaryotic replication fork are
      evolutionarily conserved.

PMID- 22144918
TI  - Randomized controlled trial for an effect of catechin-enriched green tea
      consumption on adiponectin and cardiovascular disease risk factors.
AB  - BACKGROUND: Previous observational studies have indicated that green tea (GT)
      consumption is associated with reduced mortality from cerebral infarction but not
      with mortality from cerebral hemorrhage. Therefore, we hypothesized that GT
      exerts a direct antiatherosclerotic effect without any effect on hypertension. To
      investigate this hypothesis, we focused on adiponectin that seems to be among the
      several key players in atherosclerosis. OBJECTIVE: The objective of this
      randomized controlled trial (RCT) was to assess whether the consumption of
      catechin-enriched GT affects serum adiponectin levels and cardiovascular disease
      (CVD) risk factors among apparently healthy subjects. DESIGN: A total of 51
      individuals participated in the study. Eligible participants were randomly
      assigned into GT consumption groups with either high catechin (400 mg/day) or low
      catechin (100 mg/day). The study participants were asked to stop GT consumption
      for 2 weeks (washout period), following which they were to start drinking the
      provided GT beverages everyday for 9 weeks. The outcome measures were changes in
      the adiponectin levels and CVD risk factors (body weight, body mass index, waist
      circumference, blood pressure, total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, triglyceride, fasting plasma
      glucose, as well as aspartate aminotransferase, alanine aminotransferase, gamma
      glutamyl transpeptidase, uric acid, and high-sensitive C-reactive protein).
      RESULTS: After intervention for 9 weeks, we found no significant difference
      between the high- and low catechin group with respect to changes in the serum
      adiponectin level: 0.35 ug/ml (95% confidence interval (CI): -1.03, 1.74). Also,
      no significant difference was observed between the high- and low catechin groups
      with respect to changes in any of the measured CVD risk factors. CONCLUSION: This
      RCT showed no significant difference between the high- and low catechin groups
      with respect to changes in the serum adiponectin level and any CVD risk factors.

PMID- 22144919
TI  - Video laryngoscopes.

PMID- 22144921
TI  - Erratum: ERRATA.
AB  - [This corrects the article on p. 19 in vol. 5, PMID: 21655011.][This corrects the
      article on p. 190 in vol. 5, PMID: 21804802.].

PMID- 22144920
TI  - Effects of local low-dose rocuronium on the quality of peribulbar anesthesia for
      cataract surgery.
AB  - OBJECTIVES: Peribulbar anesthesia is associated with delayed and/or incomplete
      orbital akinesia compared with retrobulbar anesthesia. This study examined the
      effects of adding rocuronium 5 mg to two different concentrations of lidocaine
      bupivacaine mixture on onset time of orbital and eyelid akinesia in patients
      undergoing cataract surgery. METHODS: In a double-blind study, 90 patients were
      equally randomized to receive a mixture of 0.5 ml normal saline, 4 ml lidocaine
      2%, and 4 ml bupivacaine 0.5% (group I), a mixture of rocuronium 0.5 ml (5 mg), 4
      ml lidocaine 2%, and 4 ml bupivacaine 0.5% (group II), or a mixture of rocuronium
      0.5 ml (5 mg), 4 ml lidocaine 1%, and 4 ml bupivacaine 0.25% (group III). Orbital
      akinesia was assessed on a 0-8 score (0 = no movement, 8 = normal) at 2 min
      intervals for 10 min. Time to adequate anesthesia was also recorded. Results are
      presented as mean+/-SD. RESULTS: Ocular movement score decreased during the
      assessment period in all groups. However, at 2 min after block administration,
      the score decreased to 4+/-2 (95% CI 3,5) in groups II and III compared with 5+/
      2 (95% CI 4,6) in group I (P<0.01). Time to adequate condition to begin surgery
      was 9.8+/-2.9 vs. 6.9+/-4.1 vs. 7.9+/-3.9 min for groups I, II, and III,
      respectively (P=0.01). CONCLUSION: The addition of rocuronium 5 mg to a mixture
      of lidocaine 2% and bupivacaine 0.5% shortened the onset time of peribulbar
      anesthesia in patients undergoing cataract surgery without causing adverse
      effects.

PMID- 22144922
TI  - Comparative evaluation of dexmedetomidine and fentanyl for epidural analgesia in
      lower limb orthopedic surgeries.
AB  - BACKGROUND AND AIMS: Opioids as epidural adjunct to local anesthetics (LA) have
      been in use since long and alpha-2 agonists are being increasingly used for
      similar purpose. The present study aims at comparing the hemodynamic, sedative,
      and analgesia potentiating effects of epidurally administered fentanyl and
      dexmedetomidine when combined with ropivacaine. METHODS: A total of one hundred
      patients of both gender aged 21-56 years, American Society of Anaesthesiologist
      (ASA) physical status I and II who underwent lower limb orthopedic surgery were
      enrolled into the present study. Patients were randomly divided into two groups:
      Ropivacaine + Dexmedetomidine (RD) and Ropivacaine + Fentanyl (RF), comprising 50
      patie nts each. Inj. Ropivacaine, 15 ml of 0.75%, was administered epidurally in
      both the groups with addition of 1 MUg/kg of dexmedetomidine in RD group and 1
      MUg/kg of fentanyl in RF group. Besides cardio-respiratory parameters and
      sedation scores, various block characteristics were also observed which included
      time to onset of analgesia at T10, maximum sensory analgesic level, time to
      complete motor blockade, time to two segmental dermatomal regressions, and time
      to first rescue analgesic. At the end of study, data was compiled systematically
      and analyzed using ANOVA with post-hoc significance, Chi-square test and Fisher's
      exact test. Value of P<0.05 is considered significant and P<0.001 as highly
      significant. RESULTS: The demographic profile of patients was comparable in both
      the groups. Onset of sensory analgesia at T10 (7.12+/-2.44 vs 9.14+/-2.94) and
      establishment of complete motor blockade (18.16+/-4.52 vs 22.98+/-4.78) was
      significantly earlier in the RD group. Postoperative analgesia was prolonged
      significantly in the RD group (366.62+/-24.42) and consequently low dose
      consumption of local anaesthetic LA (76.82+/-14.28 vs 104.35+/-18.96) during
      epidural top-ups postoperatively. Sedation scores were much better in the RD
      group and highly significant on statistical comparison (P<0.001). Incidence of
      nausea and vomiting was significantly high in the RF group (26% and 12%), while
      incidence of dry mouth was significantly higher in the RD group (14%) (P<0.05).
      CONCLUSIONS: Dexmedetomidine seems to be a better alternative to fentanyl as an
      epidural adjuvant as it provides comparable stable hemodynamics, early onset, and
      establishment of sensory anesthesia, prolonged post-op analgesia, lower
      consumption of post-op LA for epidural analgesia, and much better sedation
      levels.

PMID- 22144923
TI  - Maternal and neonatal effects of nalbuphine given immediately before induction of
      general anesthesia for elective cesarean section.
AB  - BACKGROUND: Although nalbuphine was studied extensively in labour analgesia and
      was proved to be acceptable analgesics during delivery, its use as premedication
      before induction of general anesthesia for cesarean section is not studied. The
      aim of this study was to evaluate the effect of nalbuphine given before induction
      of general anesthesia for cesarean section on quality of general anesthesia,
      maternal stress response, and neonatal outcome. METHODS: Sixty full term pregnant
      women scheduled for elective cesarean section, randomly classified into two equal
      groups, group N received nalbuphine 0.2 mg/kg diluted in 10 ml of normal saline
      (n=30), and group C placebo (n=30) received 10 ml of normal saline 1 min before
      the induction of general anesthesia. Maternal heart rate and blood pressure were
      measured before, after induction, during surgery, and after recovery. Neonates
      were assisted by using APGAR0 scores, time to sustained respiration, and
      umbilical cord blood gas analysis. RESULT: Maternal heart rate showed significant
      increase in control group than nalbuphine group after intubation (88.2+/-4.47
      versus 80.1+/-4.23, P<0.0001) and during surgery till delivery of baby (90.8+/
      2.39 versus 82.6+/-2.60, P<0.0001) and no significant changes between both groups
      after delivery. MABP increased in control group than nalbuphine group after
      intubation (100.55+/-6.29 versus 88.75+/-6.09, P<0.0001) and during surgery till
      delivery of baby (98.50+/-2.01 versus 90.50+/-2.01, P<0.0001) and no significant
      changes between both groups after delivery. APGAR score was significantly low at
      one minute in nalbuphine group than control group (6.75+/-2.3, 8.5+/-0.74,
      respectively, P=0.0002) (27% of nalbuphine group APGAR score ranged between 4-6,
      while 7% in control group APGAR score ranged between 4-6 at one minute). All
      neonates at five minutes showed APGAR score ranged between 9-10. Time to
      sustained respiration was significantly longer in nalbuphine group than control
      group (81.8+/-51.4 versus 34.9+/-26.2 seconds, P<0.0001). The umbilical cord
      blood gas was comparable in both groups. None of the neonates need opioid
      antagonist (naloxone) or endotracheal intubation. CONCLUSION: Administration of
      nalbuphine before cesarean section under general anesthesia reduces maternal
      stress response related to intubation and surgery, but decreases the APGAR score
      at one minute after delivery. So, when nalbuphine was used, all measures for
      neonatal monitoring and resuscitation must be available including attendance of a
      pediatrician.

PMID- 22144925
TI  - Addition of intrathecal Dexamethasone to Bupivacaine for spinal anesthesia in
      orthopedic surgery.
AB  - OBJECTIVES: Spinal anesthesia has the advantage that profound nerve block can be
      produced in a large part of the body by the relatively simple injection of a
      small amount of local anesthetic. Intrathecal local anesthetics have limited
      duration. Different additives have been used to prolong spinal anesthesia. The
      effect of corticosteroids in prolonging the analgesic effects of local
      anesthetics in peripheral nerves is well documented. The purpose of this
      investigation was to determine whether the addition of dexamethasone to
      intrathecal bupivacaine would prolong the duration of sensory analgesia or not.
      METHODS: We conducted a randomized, prospective, double-blind, case-control,
      clinical trial. A total of 50 patients were scheduled for orthopedic surgery
      under spinal anesthesia. The patients were randomly allocated to receive 15 mg
      hyperbaric bupivacaine 0.5% with 2 cc normal saline (control group) or 15 mg
      hyperbaric bupivacaine 0.5% plus 8 mg dexamethasone (case group) intrathecally.
      The patients were evaluated for quality, quantity, and duration of block; blood
      pressure, heart rate, nausea, and vomiting or other complications. RESULTS: There
      were no signification differences in demographic data, sensory level, and onset
      time of the sensory block between two groups. Sensory block duration in the case
      group was 119+/-10.69 minutes and in the control group was 89.44+/-8.37 minutes
      which was significantly higher in the case group (P<0.001). The duration of
      analgesia was 401.92+/-72.44 minutes in the case group; whereas it was 202+/
      43.67 minutes in the control group (P<0.001). The frequency of complications was
      not different between two groups. CONCLUSION: This study has shown that the
      addition of intrathecal dexamethasone to bupivacaine significantly improved the
      duration of sensory block in spinal anesthesia without any changes in onset time
      and complications.

PMID- 22144924
TI  - Use of Airtraq, C-Mac, and Glidescope laryngoscope is better than Macintosh in
      novice medical students' hands: A manikin study.
AB  - BACKGROUND AND AIM: Obtaining patent airway is a crucial task for many
      physicians. When opportunities to practice intubations on patients are really
      limited, skill gaining methods are needed. We conducted a study among novice
      6(th) year medical students to assess their ability to intubate the trachea in
      normal airway in manikin using four airway tools. SETTING AND DESIGN:
      Prospective, cohort study conducted at simulation center of university-based,
      tertiary care hospital. METHODS: FIFTY MEDICAL STUDENTS PERFORMED EITHER ORAL OR
      NASAL TRACHEAL INTUBATION USING THE FOLLOWING FOUR INTUBATING TOOLS: C-Mac
      videolaryngoscope, Glidescope, and Airtraq in comparison with regular Macintosh
      laryngoscope. Intubation time, visualization of glottic opening, ease of
      intubation, satisfaction of participants, incidence of dental trauma, and the
      need for optimization manoeuvres' use among different airway tools were recorded.
      RESULTS: In oral intubation, Airtraq was better than others in regard to
      intubation time, glottic opening, ease of intubation, and the need for external
      laryngeal pressure application, followed by Glidescope, C-Mac, and finally
      Macintosh laryngoscope (P<0.001). Airtraq and Glidescope associated with less
      dental trauma than C-Mac and Macintosh. In nasal route, fastest intubation time
      was reported with Airtraq followed by Glidescope, C-Mac, and lastly Macintosh.
      Airtraq, Glidescope, and C-Mac were similar to each other and better than the
      Macintosh in regard to ease of intubation, satisfaction, and number of attempts
      (P<=0.008). CONCLUSIONS: New devices like Airtraq, Glidescope, and C-Mac are
      better than the regular Macintosh when used by novice medical students for oral
      and nasal intubation on manikin.

PMID- 22144926
TI  - Preanesthetic medication in children: A comparison of intranasal dexmedetomidine
      versus oral midazolam.
AB  - BACKGROUND: Relieving preoperative anxiety is an important concern for the
      pediatric anesthesiologist. Midazolam has become the most frequently used
      premedication in children. However, new drugs such as the alpha(2) -agonists have
      emerged as alternatives for premedication in pediatric anesthesia. METHODS: One
      hundred and twenty children scheduled for adenotonsillectomy were enrolled in
      this prospective, double-blind, randomized study. The children were divided into
      two equal groups to receive either intranasal dexmedetomidine 1 MUg/kg (group D),
      or oral midazolam 0.5 mg/kg (group M) at approximately 60 and 30 mins,
      respectively, before induction of anesthesia. Preoperative sedative effects,
      anxiety level changes, and the ease of child-parent separation were assessed.
      Also, the recovery profile and postoperative analgesic properties were assessed.
      RESULTS: Children premedicated with intranasal dexmedetomidine achieved
      significantly lower sedation levels (P=0.042), lower anxiety levels (P=0.036),
      and easier child-parent separation (P=0.029) than children who received oral
      midazolam at the time of transferring the patients to the operating room.
      Postoperatively, the time to achieve an Aldrete score of 10 was similar in both
      the groups (P=0.067). Also, the number of children who required fentanyl as
      rescue analgesia medication was significantly less (P=0.027) in the
      dexmedetomidine group. CONCLUSION: Intranasal dexmedetomidine appears to be a
      better choice for preanesthetic medication than oral midazolam in our study.
      Dexmedetomidine was associated with lower sedation levels, lower anxiety levels,
      and easier child-parent separation at the time of transferring patients to the
      operating room than children who received oral midazolam. Moreover, intranasal
      dexmedetomidine has better analgesic property than oral midazolam with discharge
      time from postanesthetic care unit similar to oral midazolam.

PMID- 22144927
TI  - Ultrasound guidance of uncommon nerve blocks.
AB  - In the past nerve stimulation was considered the standard tool for
      anesthesiologists to locate the peripheral nerve for nerve blocks. However, with
      the recent introduction of ultrasound (US) technology for regional anesthesia,
      the use of nerve stimulation has become a rarity nowadays. There is a growing
      interest by most anesthesiologists in using US for nerve blocks because of its
      simplicity and accuracy. US is now available in most hospitals practicing
      regional anesthesia and is a popular tool for performance of nerve blocks.
      Although nerve stimulation became a rarity, however the use of it is now limited
      to identify small nerve structures, such as greater auricular nerve and medial
      antebrachial cutaneous nerve of the forearm. However, in this review article we
      discuss the role of ultrasonography for greater auricular and antebrachial
      cutaneous nerve blocks, which could replace nerve stimulation technique. We look
      at the available literature on the role of US for the performance of uncommon
      nerve blocks and its benefits.

PMID- 22144929
TI  - The SensaScope- A new hybrid video intubation stylet.
AB  - The recently developed SensaScope((r)) is a hybrid intubation endoscope that has
      been designed and developed according to our clinical requirements for a safe,
      easy-to-handle, and effective video-assisted intubation. The attribute "hybrid"
      derives from the fact that the shaft of the instrument is combined by both, rigid
      and flexible parts. Its S-shaped rigid segment enables a very intuitive handling
      by one hand only, thus leaving the left hand free to operate a conventional
      laryngoscope. The tip of the device can be controlled via a steering handle in a
      similar fashion as fiberoptic endoscopes. Due to these attributes, the
      SensaScope((r)) became a very versatile and effective tool to master the
      unanticipated difficult intubation in anesthetized and paralyzed patients. For
      this reason, in our institution it has been included as the first-line technique
      into our local failed intubation algorithm. The first clinical experience with
      the device and its standardized technique of use produced encouraging results;
      the success rate for novices was found to be at 97% (in 194 of 200 patients) of
      all intubation attempts in both patients categories: those who were rated as
      having normal (84.5%) and in those showing difficult intubation conditions
      (15.5%). The technical development, the way of using the device, the suitable
      indications, and limitations are discussed here.

PMID- 22144930
TI  - Intubation in a pediatric difficult airway using an adult flexible fiber-optic
      bronchoscope and a j-tipped guidewire: An innovation in adversity.
AB  - Management of an anticipated difficult airway relies heavily on flexible fiber
      optic bronchoscope (FFB) guided awake intubations. In a pediatric patient with
      difficult airway, doing an awake procedure may be difficult, and hence the child
      is either deeply sedated or anesthesia is induced before attempting intubation
      with an appropriate sized FFB. We present the anesthetic management of a 6-year
      old child with a lacerated tongue and fractured mandibular condyle, with
      subsequent inability to open his mouth, who was posted for urgent exploration and
      open reduction under anesthesia. Unhindered by a damaged pediatric FFB, we
      innovated by positioning the tip of an adult FFB just outside the larynx, passing
      a j-tipped guidewire through the working channel of the FFB, and successfully
      railroaded a naso-tracheal tube over the guidewire. The surgery, reversal and
      extubation, and the postoperative period were uneventful.

PMID- 22144931
TI  - Accidental five fold overdose of propofol for induction in a 38-days-old infant
      undergoing emergency bilateral inguinal hernia repair.
AB  - The induction dose of propofol is higher in younger children (2.9 mg/kg for
      infants younger than 2 years) than in older children (2.2 mg/kg for children 6-12
      years of age). A modest reduction in systolic blood pressure often accompanies
      bolus administration. The major concern with propofol is the potential for
      propofol infusion syndrome (lactic acidosis, rhabdomyolysis, cardiac and renal
      failure), which is generally associated with high-dose infusion for an extended
      period. We report a 38-days-old male infant underwent emergency bilateral
      inguinal hernia repair who accidentally received a five-fold dose of propofol for
      induction of general anesthesia.

PMID- 22144928
TI  - Procedural sedation: A review of sedative agents, monitoring, and management of
      complications.
AB  - Given the continued increase in the complexity of invasive and noninvasive
      procedures, healthcare practitioners are faced with a larger number of patients
      requiring procedural sedation. Effective sedation and analgesia during procedures
      not only provides relief of suffering, but also frequently facilitates the
      successful and timely completion of the procedure. However, any of the agents
      used for sedation and/or analgesia may result in adverse effects. These adverse
      effects most often affect upper airway patency, ventilatory function or the
      cardiovascular system. This manuscript reviews the pharmacology of the most
      commonly used agents for sedation and outlines their primary effects on
      respiratory and cardiovascular function. Suggested guidelines for the avoidance
      of adverse effects through appropriate pre-sedation evaluation, early
      identification of changes in respiratory and cardiovascular function, and their
      treatment are outlined.

PMID- 22144932
TI  - Difficult intubation in a parturient with syringomyelia and Arnold-Chiari
      malformation: Use of Airtraq laryngoscope.
AB  - Anesthetic technique in parturient with syringomyelia and Arnold-Chiari
      malformation is variable depending on the teams. Difficult intubation is one of
      the risks when general anesthesia is opted. Different devices have been used to
      manage the difficult intubation in pregnant women. We report the use of AirtraqTM
      laryngoscope after failed standard laryngoscopy in a parturient with
      syringomyelia and Arnold-Chiari type I malformation.

PMID- 22144933
TI  - Awake intubation with Bonfil's retromolar fibroscope in a patient with hard and
      fixed swelling of the right side of the neck and the tonsillar tumor.
AB  - Bonfil's rigid fibroscope is an instrument used to perform tracheal intubation,
      proven to be effective both in patients with normal and in those with difficult
      airways. We use this device in awake intubation in a patient presenting with a
      large right neck mass and a tonsillar tumor which limited the mouth opening.
      Also, we describe our technique of insertion of Bonfil's retromolar fibroscope
      from the right side of the mouth across the tongue.

PMID- 22144934
TI  - Dexmedetomidine as the primary anesthetic agent during cardiac surgery in an
      infant with a family history of malignant hyperthermia.
AB  - Malignant hyperthermia (MH) is an acute hypermetabolic crisis triggered in
      susceptible patients by the administration of succinylcholine or a volatile
      anesthetic agent. When providing anesthetic care for MH-susceptible agents, a
      total intravenous anesthetic (TIVA) technique is frequently chosen. When choosing
      the components for TIVA, several options exist including the combination of
      propofol or dexmedetomidine with an opioid. We present our experience with the
      use of dexmedetomidine as a key component of the anesthetic regimen in a 5-month
      old infant with a family history of MH. Previous reports of the use of
      dexmedetomidine in MH-susceptible patients are reviewed and its benefits in such
      patients discussed.

PMID- 22144935
TI  - Anesthetic management in a patient with Kindler's syndrome.
AB  - A 35-year-old male with pan-anterior urethral stricture was scheduled to undergo
      perineal urethrostomy. He was a known case of Kindler's syndrome since infancy.
      He was having a history of blister formation, extensive poikiloderma and
      progressive cutaneous atrophy since childhood. He had a tendency of trauma
      induced blisters with clear or hemorrhagic contents that healed with scarring.
      The fingers were sclerodermiform with dystrophic nails and inability to
      completely clench the fist. Airway examination revealed thyromental distance of 7
      cm with limited neck extension, limited mouth opening and mallampatti class III
      with a fixed large tongue. He was reported as grade IV Cormack and Lehane
      laryngoscopic on previous anesthesia exposure. We described the anesthetic
      management of such case on guidelines for epidermolysis bullosa. In the operating
      room, an 18-G cannula was secured in the right upper limb using Coban(TM) Wrap.
      The T-piece of the cannula was than inserted into the slit and the tape was
      wrapped around the extremity. The ECG electrodes were placed on the limbs and
      fixed with Coban(TM). Noninvasive blood pressure cuff was applied over the wrap
      after wrapping the arm with Webril((r)) cotton. Oral fiberoptic tracheal
      intubation was done after lubricating the laryngoscope generously with a water
      based lubricant with 7-mm endotracheal tube. Surgery proceeded without any
      complication. After reversing the residual neuromuscular block, trachea was
      extubated once the patient became awake. He was kept in the postanesthesia care
      unit for 2 hours and then shifted to urology ward.

PMID- 22144936
TI  - Broncho-pleuropericardial fistula complicating staphylococcal sepsis.
AB  - This is a rare case of broncho-pleuropericardial fistula in a 12-year-old female
      who presented with fever, painful joint swelling, and pleural and pericardial
      effusion secondary to disseminated methicillin-sensitive Staphylococcus aureus
      infection. The pleural and pericardial effusion were drained, however, air leak
      was observed from both tubes and was synchronous with mechanical inspiration. A
      broncho-pleuropericardial fistula was suspected and confirmed with computed
      tomography. This case report demonstrated that disseminated S. aureus bacteremia
      could result in broncho-pleuropericardial fistula. The ability of disseminated
      staphylococcal infection to produce pnemopericardium should be added to the list
      of other complications associated with disseminated staphylococcal sepsis.

PMID- 22144937
TI  - Application of indigenous continuous positive airway pressure during one lung
      ventilation for thoracic surgery.
AB  - During one lung ventilation (OLV) hypoxemia may occur due to ventilation
      perfusion mismatch. It can be prevented with application of ventilation strategy
      that prevents atelectasis while minimally impairing perfusion of the dependant
      lung. Here, two cases are reported who required OLV and in whom hypoxemia could
      be prevented with the application of continuous positive airway pressure to the
      deflated or non-dependant lung, using an indigenous technique. We suggest use of
      this technique which is easy to be employed during the intraoperative period.

PMID- 22144938
TI  - Tracheal intubation with nasal speculum in situ.

PMID- 22144939
TI  - Gastric tube connector: A simple solution for everyday problem.

PMID- 22144940
TI  - An alternative to bite block in a patient with restricted mouth opening.

PMID- 22144941
TI  - Intraoperative anuria: An unusual cause.

PMID- 22144942
TI  - Use of nasopharyngeal airway for interim dilatation of lower tracheal stenosis.

PMID- 22144943
TI  - Guess what?

PMID- 22144944
TI  - Prior knowledge improves decoding of finger flexion from electrocorticographic
      signals.
AB  - Brain-computer interfaces (BCIs) use brain signals to convey a user's intent.
      Some BCI approaches begin by decoding kinematic parameters of movements from
      brain signals, and then proceed to using these signals, in absence of movements,
      to allow a user to control an output. Recent results have shown that
      electrocorticographic (ECoG) recordings from the surface of the brain in humans
      can give information about kinematic parameters (e.g., hand velocity or finger
      flexion). The decoding approaches in these studies usually employed classical
      classification/regression algorithms that derive a linear mapping between brain
      signals and outputs. However, they typically only incorporate little prior
      information about the target movement parameter. In this paper, we incorporate
      prior knowledge using a Bayesian decoding method, and use it to decode finger
      flexion from ECoG signals. Specifically, we exploit the constraints that govern
      finger flexion and incorporate these constraints in the construction, structure,
      and the probabilistic functions of the prior model of a switched non-parametric
      dynamic system (SNDS). Given a measurement model resulting from a traditional
      linear regression method, we decoded finger flexion using posterior estimation
      that combined the prior and measurement models. Our results show that the
      application of the Bayesian decoding model, which incorporates prior knowledge,
      improves decoding performance compared to the application of a linear regression
      model, which does not incorporate prior knowledge. Thus, the results presented in
      this paper may ultimately lead to neurally controlled hand prostheses with full
      fine-grained finger articulation.

PMID- 22144946
TI  - PI3K/AKT/mTOR Pathway in Angiogenesis.
AB  - The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR)
      pathway is activated in the majority of human cancers. This pathway is known to
      play a key role in numerous cellular functions including proliferation, adhesion,
      migration, invasion, metabolism, and survival, but in the current review we focus
      on its role in angiogenesis. PI3K activation may occur via RAS mutation, loss of
      phosphatase and tensin homolog (PTEN), or by increased expression of growth
      factor receptors such as epidermal growth factor receptor. There is a connection
      between the PI3K pathway and angiogenesis. Hypoxia leads to HIF-1alpha
      stabilization and is a major stimulus for increased vascular endothelial growth
      factor (VEGF) production by tumor cells. However, activation of the PI3K/AKT
      pathway in tumor cells can also increase VEGF secretion, both by hypoxia
      inducible factor 1 (HIF-1) dependent and independent mechanisms. The PI3K/AKT
      pathway also modulates the expression of other angiogenic factors such as nitric
      oxide and angiopoietins. Numerous inhibitors targeting the PI3K/AKT/mTOR pathway
      have been developed, and these agents have been shown to decrease VEGF secretion
      and angiogenesis. The effect of these inhibitors on tumor vasculature can be
      difficult to predict. The vasculature of tumors is aberrant, leading to sluggish
      bloodflow and elevated interstitial blood pressure, which can be perpetuated by
      the high levels of VEGF. Hence, decreasing VEGF expression can paradoxically lead
      to vascular normalization and improved bloodflow in some tumors. In addition to
      its importance in cancer, the PI3K pathway also plays an essential role in the
      formation of normal blood vessels during development. Embryos with kinase-dead
      p110alpha catalytic subunit of PI3K develop vascular defects. Stimulation of
      endothelial cells by VEGF leads to activation of the PI3K pathway within these
      cells, which is important for cell migration. Sustained endothelial activation of
      AKT1 has been shown to induce the formation of structurally abnormal blood
      vessels that recapitulate the aberrations of tumor vessels. Hence, the PI3K
      pathway plays an important role in regulating angiogenesis both in normal tissues
      and in cancers.

PMID- 22144945
TI  - Activity-dependent plasticity and gene expression modifications in the adult CNS.
AB  - Information processing, memory formation, or functional recovery after nervous
      system damage depend on the ability of neurons to modify their functional
      properties or their connections. At the cellular/molecular level, structural
      modifications of neural circuits are finely regulated by intrinsic neuronal
      properties and growth-regulatory cues in the extracellular milieu. Recently, it
      has become clear that stimuli coming from the external world, which comprise
      sensory inflow, motor activity, cognitive elaboration, or social interaction, not
      only provide the involved neurons with instructive information needed to shape
      connection patterns to sustain adaptive function, but also exert a powerful
      influence on intrinsic and extrinsic growth-related mechanisms, so to create
      permissive conditions for neuritic remodeling. Here, we present an overview of
      recent findings concerning the effects of experience on molecular mechanisms
      underlying CNS structural plasticity, both in physiological conditions and after
      damage, with particular focus on activity-dependent modulation of growth
      regulatory genes and epigenetic modifications.

PMID- 22144948
TI  - In vivo Labeling of Constellations of Functionally Identified Neurons for
      Targeted in vitro Recordings.
AB  - Relating the functional properties of neurons in an intact organism with their
      cellular and synaptic characteristics is necessary for a mechanistic
      understanding of brain function. However, while the functional properties of
      cortical neurons (e.g., tuning to sensory stimuli) are necessarily determined in
      vivo, detailed cellular and synaptic analysis relies on in vitro techniques. Here
      we describe an approach that combines in vivo calcium imaging (for functional
      characterization) with photo-activation of fluorescent proteins (for neuron
      labeling), thereby allowing targeted in vitro recording of multiple neurons with
      known functional properties. We expressed photo-activatable GFP rendered non
      diffusible through fusion with a histone protein (H2B-PAGFP) in the mouse visual
      cortex to rapidly photo-label constellations of neurons in vivo at cellular and
      sub-cellular resolution using two-photon excitation. This photo-labeling method
      was compatible with two-photon calcium imaging of neuronal responses to visual
      stimuli, allowing us to label constellations of neurons with specific functional
      properties. Photo-labeled neurons were easily identified in vitro in acute brain
      slices and could be targeted for whole-cell recording. We also demonstrate that
      in vitro and in vivo image stacks of the same photo-labeled neurons could be
      registered to one another, allowing the exact in vivo response properties of
      individual neurons recorded in vitro to be known. The ability to perform in vitro
      recordings from neurons with known functional properties opens up exciting new
      possibilities for dissecting the cellular, synaptic, and circuit mechanisms that
      underlie neuronal function in vivo.

PMID- 22144947
TI  - New perspectives in amblyopia therapy on adults: a critical role for the
      excitatory/inhibitory balance.
AB  - Amblyopia is the most common form of impairment of visual function affecting one
      eye, with a prevalence of about 1-5% of the total world population. This
      pathology is caused by early abnormal visual experience with a functional
      imbalance between the two eyes owing to anisometropia, strabismus, or congenital
      cataract, resulting in a dramatic loss of visual acuity in an apparently healthy
      eye and various other perceptual abnormalities, including deficits in contrast
      sensitivity and in stereopsis. It is currently accepted that, due to a lack of
      sufficient plasticity within the brain, amblyopia is untreatable in adulthood.
      However, recent results obtained both in clinical trials and in animal models
      have challenged this traditional view, unmasking a previously unsuspected
      potential for promoting recovery after the end of the critical period for visual
      cortex plasticity. These studies point toward the intracortical inhibitory
      transmission as a crucial brake for therapeutic rehabilitation and recovery from
      amblyopia in the adult brain.

PMID- 22144949
TI  - Genetically induced cholinergic hyper-innervation enhances taste learning.
AB  - Acute inhibition of acetylcholine (ACh) has been shown to impair many forms of
      simple learning, and notably conditioned taste aversion (CTA). The most adhered
      to theory that has emerged as a result of this work - that ACh increases a
      taste's perceived novelty, and thereby its associability - would be further
      strengthened by evidence showing that enhanced cholinergic function improves
      learning above normal levels. Experimental testing of this corollary hypothesis
      has been limited, however, by side-effects of pharmacological ACh agonism and by
      the absence of a model that achieves long-term increases in cholinergic
      signaling. Here, we present this further test of the ACh hypothesis, making use
      of mice lacking the p75 pan-neurotrophin receptor gene, which show a resultant
      over-abundance of cholinergic neurons in sub-regions of the basal forebrain (BF).
      We first demonstrate that the p75-/- abnormality directly affects portions of the
      CTA circuit, locating mouse gustatory cortex (GC) using a functional assay and
      then using immunohistochemisty to demonstrate cholinergic hyper-innervation of GC
      in the mutant mice - hyper-innervation that is unaccompanied by changes in cell
      numbers or compensatory changes in muscarinic receptor densities. We then
      demonstrate that both p75-/- and wild-type (WT) mice learn robust CTAs, which
      extinguish more slowly in the mutants. Further testing to distinguish effects on
      learning from alterations in memory retention demonstrate that p75-/- mice do in
      fact learn stronger CTAs than WT mice. These data provide novel evidence for the
      hypothesis linking ACh and taste learning.

PMID- 22144950
TI  - Sweet taste signaling and the formation of memories of energy sources.
AB  - The last decade witnessed remarkable advances in our knowledge of the gustatory
      system. Application of molecular biology techniques not only determined the
      identity of the membrane receptors and downstream effectors that mediate
      sweetness, but also uncovered the overall logic of gustatory coding in the
      periphery. However, while the ability to taste sweet may offer the obvious
      advantage of eliciting rapid and robust intake of sugars, a number of recent
      studies demonstrate that sweetness is neither necessary nor sufficient for the
      formation of long-lasting preferences for stimuli associated with sugar intake.
      Furthermore, uncoupling sweet taste from ensuing energy utilization may disrupt
      body weight control. This minireview examines recent experiments performed in
      both rodents and Drosophila revealing the taste-independent rewarding properties
      of metabolizable sugars. Taken together, these experiments demonstrate the
      reinforcing actions of sugars in the absence of sweet taste signaling and point
      to a critical role played by dopamine systems in translating metabolic sensing
      into behavioral action. From a mechanistic viewpoint, current evidence favors the
      concept that gastrointestinal and post-absorptive signals contribute in parallel
      to sweet-independent sugar acceptance and dopamine release.

PMID- 22144951
TI  - Adaptive timing of motor output in the mouse: the role of movement oscillations
      in eyelid conditioning.
AB  - To survive, animals must learn to control their movements with millisecond-level
      precision, and adjust the kinematics if conditions, or task requirements, change.
      Here, we examine adaptive timing of motor output in mice, using a simple eyelid
      conditioning task. Mice were trained to blink in response to a light stimulus
      that was always followed by a corneal air-puff at a constant time interval.
      Different mice were trained with different intervals of time separating the onset
      of the light and the air-puff. As in previous work in other animal species, mice
      learned to control the speed of the blink, such that the time of maximum eyelid
      closure matched the interval used during training. However, we found that the
      time of maximum eyelid speed was always in the first 100 ms after movement onset
      and did not scale with the training interval, indicating that adaptive timing is
      not accomplished by slowing down (or speeding up) the eyelid movement uniformly
      throughout the duration of the blink. A new analysis, specifically designed to
      examine the kinematics of blinks in single trials, revealed that the underlying
      control signal responsible for the eyelid movement is made up of oscillatory
      bursts that are time-locked to the light stimulus at the beginning of the blink,
      becoming desynchronized later on. Furthermore, mice learn to blink at different
      speeds and time the movement appropriately by adjusting the amplitude, but not
      the frequency of the bursts in the eyelid oscillation.

PMID- 22144952
TI  - Temporal accumulation and decision processes in the duration bisection task
      revealed by contingent negative variation.
AB  - The duration bisection paradigm is a classic task used to examine how humans and
      other animals perceive time. Typically, participants first learn short and long
      anchor durations and are subsequently asked to classify probe durations as closer
      to the short or long anchor duration. However, the specific representations of
      time and the decision rules applied in this task remain the subject of debate.
      For example, researchers have questioned whether participants actually use
      representations of the short and long anchor durations in the decision process
      rather than merely a response threshold that is derived from those anchor
      durations. Electroencephalographic (EEG) measures, like the contingent negative
      variation (CNV), can provide information about the perceptual and cognitive
      processes that occur between the onset of the timing stimulus and the motor
      response. The CNV has been implicated as an electrophysiological marker of
      interval timing processes such as temporal accumulation, representation of the
      target duration, and the decision that the target duration has been attained. We
      used the CNV to investigate which durations are involved in the bisection
      categorization decision. The CNV increased in amplitude up to the value of the
      short anchor, remained at a constant level until about the geometric mean (GM) of
      the short and long anchors, and then began to resolve. These results suggest that
      the short anchor and the GM of the short and long anchors are critical target
      durations used in the bisection categorization decision process. In addition,
      larger mean N1P2 amplitude differences were associated with larger amplitude
      CNVs, which may reflect the participant's precision in initiating timing on each
      trial across a test session. Overall, the results demonstrate the value of using
      scalp-recorded EEG to address basic questions about interval timing.

PMID- 22144953
TI  - High-level binocular rivalry effects.
AB  - Binocular rivalry (BR) occurs when the brain cannot fuse percepts from the two
      eyes because they are different. We review results relating to an ongoing
      controversy regarding the cortical site of the BR mechanism. Some BR qualities
      suggest it is low-level: (1) BR, as its name implies, is usually between eyes and
      only low-levels have access to utrocular information. (2) All input to one eye is
      suppressed: blurring doesn't stimulate accommodation; pupilary constrictions are
      reduced; probe detection is reduced. (3) Rivalry is affected by low-level
      attributes, contrast, spatial frequency, brightness, motion. (4) There is limited
      priming due to suppressed words or pictures. On the other hand, recent studies
      favor a high-level mechanism: (1) Rivalry occurs between patterns, not eyes, as
      in patchwork rivalry or a swapping paradigm. (2) Attention affects alternations.
      (3) Context affects dominance. There is conflicting evidence from physiological
      studies (single cell and fMRI) regarding cortical level(s) of conscious
      perception. We discuss the possibility of multiple BR sites and theoretical
      considerations that rule out this solution. We present new data regarding the
      locus of the BR switch by manipulating stimulus semantic content or high-level
      characteristics. Since these variations are represented at higher cortical
      levels, their affecting rivalry supports high-level BR intervention. In
      Experiment I, we measure rivalry when one eye views words and the other non-words
      and find significantly longer dominance durations for non-words. In Experiment
      II, we find longer dominance times for line drawings of simple, structurally
      impossible figures than for similar, possible objects. In Experiment III, we test
      the influence of idiomatic context on rivalry between words. Results show that
      generally words within their idiomatic context have longer mean dominance
      durations. We conclude that BR has high-level cortical influences, and may be
      controlled by a high-level mechanism.

PMID- 22144954
TI  - The lateralization of motor cortex activation to action-words.
AB  - What determines the laterality of activation in motor cortex for words whose
      meaning is related to bodily actions? It has been suggested that the neuronal
      representation of the meaning of action-words is shaped by individual experience.
      However, core language functions are left-lateralized in the majority of both
      right- and left-handers. It is still an open question to what degree connections
      between left-hemispheric core language areas and right-hemispheric motor areas
      can play a role in semantics. We investigated laterality of brain activation
      using fMRI in right- and left-handed participants in response to visually
      presented hand-related action-words, namely uni- and bi-manual actions (such as
      "throw" and "clap"). These stimulus groups were matched with respect to general
      (hand-) action-relatedness, but differed with respect to whether they are usually
      performed with the dominant hand or both hands. We may expect generally more left
      hemispheric motor cortex activation for hand-related words in both handedness
      groups, with possibly more bilateral activation for left-handers compared to
      right-handers. In our study, both participant groups activated motor cortex
      bilaterally for bi-manual words. Interestingly, both groups also showed a left
      lateralized activation pattern to uni-manual words. We argue that this reflects
      the effect of left-hemispheric language dominance on the formation of semantic
      brain circuits on the basis of Hebbian correlation learning.

PMID- 22144955
TI  - Two systems of non-symbolic numerical cognition.
AB  - Studies of human adults, infants, and non-human animals demonstrate that non
      symbolic numerical cognition is supported by at least two distinct cognitive
      systems: a "parallel individuation system" that encodes the numerical identity of
      individual items and an "approximate number system" that encodes the approximate
      numerical magnitude, or numerosity, of a set. The exact nature and role of these
      systems, however, have been debated for over a 100-years. Some argue that the non
      symbolic representation of small numbers (<4) is carried out solely by the
      parallel individuation system and the non-symbolic representation of large
      numbers (>4) is carried out solely by the approximate number system. Others argue
      that all numbers are represented by the approximate number system. This debate
      has been fueled largely by some studies showing dissociations between small and
      large number processing and other studies showing similar processing of small and
      large numbers. Recent work has addressed this debate by showing that the two
      systems are present and distinct from early infancy, persist despite the
      acquisition of a symbolic number system, activate distinct cortical networks, and
      engage differentially based attentional constraints. Based on the recent
      discoveries, I provide a hypothesis that may explain the puzzling findings and
      makes testable predictions as to when each system will be engaged. In particular,
      when items are presented under conditions that allow selection of individuals,
      they will be represented as distinct mental items through parallel individuation
      and not as a numerical magnitude. In contrast, when items are presented outside
      attentional limits (e.g., too many, too close together, under high attentional
      load), they will be represented as a single mental numerical magnitude and not as
      distinct mental items. These predictions provide a basis on which researchers can
      further investigate the role of each system in the development of uniquely human
      numerical thought.

PMID- 22144956
TI  - Neural correlates of inter-trial priming and role-reversal in visual search.
AB  - Studies of priming of visual perception demonstrate that observers respond more
      quickly to targets in a field of distractors when relevant features are repeated
      versus novel or role-reversed. In a recent brain imaging study by Kristjansson et
      al. (2007), participants were presented with two items of one color and a single
      item in a different color with the task of reporting the orientation of the
      uniquely colored item. Consistent with previous behavioral reports, they found
      that observers were faster to respond when the target and distractor colors were
      identical to the previous trial than when they were reversed. They found reduced
      BOLD activity in brain areas linked with attentional control on trials where the
      target and distractor colors were repeated relative to reversed, which they
      interpreted as reflecting response suppression (decreased BOLD signal for
      repeated stimuli). However, since their design only compared repeated versus
      reversed task demands, it is logically possible that this pattern reflects
      increased BOLD signal for role-reversed stimuli: activity required to inhibit
      previously facilitated information and select previously inhibited information.
      We explored this possibility with a task where we contrasted the signal generated
      by repeated, reversed, and novel features. Our data suggest that the majority of
      the change in neural signal elicited by priming of pop-out reflects increased
      activation when selection criteria are reversed.

PMID- 22144957
TI  - Disparity Context Processing in the Primate Brain: And If the Question was Both
      "What" and "When"....

PMID- 22144959
TI  - Visual Object Categorization in the Brain: What Can We Really Learn from ERP
      Peaks?

PMID- 22144958
TI  - Understanding attentional modulation of binocular rivalry: a framework based on
      biased competition.
AB  - Starting from early scientific explorations of binocular rivalry, researchers
      have wondered about the degree to which an observer can exert voluntary
      attentional control over rivalry dynamics. The answer to this question would not
      only reveal the extent to which we may determine our own conscious visual
      experience, but also advance our understanding of the neural mechanisms
      underlying binocular rivalry. Classic studies, intriguingly, reached
      contradictory conclusions, ranging from an absence of attentional control, as
      advocated by Breese, to nearly complete control of rivalry dynamics, as reported
      by Helmholtz. Recent investigations have revisited this question, but the results
      have continued to echo the conflicting findings of earlier studies, seemingly
      precluding a comprehensive understanding of attentional effects on rivalry. Here,
      we review both classic and modern studies, and propose a unifying framework
      derived from the biased competition theory of attention. The key assumption of
      this theory is that the nature of stimulus conflict determines the limits of
      attentional modulation. For example, a condition in which unresolved stimulus
      conflict transpires through many levels of visual processing should be very
      susceptible to attentional control. When applied to binocular rivalry, this
      framework predicts strong attentional modulations under conditions of unresolved
      stimulus conflict (e.g., initial selection) and conditions where conflict is
      resolved at higher levels of visual processing (e.g., stimulus rivalry).
      Additionally, the efficacy of attentional control over rivalry can be increased
      by utilization of demanding, behaviorally relevant tasks, and likely through
      perceptual training paradigms. We show that this framework can help facilitate
      the understanding and synthesis of a diverse set of results on attentional
      control over rivalry, and we propose several directions for future research on
      this interesting topic.

PMID- 22144960
TI  - History of innate immunity in neurodegenerative disorders.
AB  - The foundations of innate immunity in neurodegenerative disorders were first laid
      by Del Rio Hortega (1919). He identified and named microglia, recognizing them as
      cells of mesodermal origin. Van Furth in 1969 elaborated the monocyte phagocytic
      system with microglia as the brain representatives. Validation of these concepts
      did not occur until 1987 when HLA-DR was identified on activated microglia in a
      spectrum of neurological disorders. HLA-DR had already been established as a
      definitive marker of immunocompetent cells of mesodermal origin. It was soon
      determined that the observed inflammatory reaction was an innate immune response.
      A rapid expansion of the field took place as other markers of an innate immune
      response were found that were made by neurons, astrocytes, oligodendroglia, and
      endothelial cells. The molecules included complement proteins and their
      regulators, inflammatory cytokines, chemokines, acute phase reactants,
      prostaglandins, proteases, protease inhibitors, coagulation factors, fibrinolytic
      factors, anaphylatoxins, integrins, free radical generators, and other
      unidentified neurotoxins. The Nimmerjahn movies demonstrated that resting
      microglia were constantly active, sampling the surround, and responding rapidly
      to brain damage. Ways of reducing the neurotoxic innate immune response and
      stimulating a healing response continue to be sought as a means for ameliorating
      the pathology in a spectrum of chronic degenerative disorders.

PMID- 22144962
TI  - A computational investigation of cardiac caveolae as a source of persistent
      sodium current.
AB  - Recent studies of cholesterol-rich membrane microdomains, called caveolae, reveal
      that caveolae are reservoirs of "recruitable" sodium ion channels. Caveolar
      channels constitute a substantial and previously unrecognized source of sodium
      current in cardiac cells. In this paper we model for the first time caveolar
      sodium currents and their contributions to cardiac action potential morphology.
      We show that the beta-agonist-induced opening of caveolae may have substantial
      impacts on peak overshoot, maximum upstroke velocity, and ultimately conduction
      velocity. Additionally, we show that prolonged action potentials and the
      formation of potentially arrhythmogenic afterdepolarizations, can arise if
      caveolae open intermittently throughout the action potential. Our simulations
      suggest that caveolar sodium current may constitute a route, which is independent
      of channelopathies, to delayed repolarization and the arrhythmias associated with
      such delays.

PMID- 22144963
TI  - New methods for the analysis of heartbeat behavior in risk stratification.
AB  - Developing better methods for risk stratification for tachyarrhythmic sudden
      cardiac remains a major challenge for physicians and scientists. Since the
      transition from sinus rhythm to ventricular tachycardia/fibrillation happens by
      different mechanisms in different people, it is unrealistic to think that a
      single measure will be adequate to provide a good index for risk stratification.
      We analyze the dynamical properties of ventricular premature complexes over 24 h
      in an effort to understand the underlying mechanisms of ventricular arrhythmias
      and to better understand the arrhythmias that occur in individual patients. Two
      dimensional density plots, called heartprints, correlate characteristic features
      of the dynamics of premature ventricular complexes and the sinus rate.
      Heartprints show distinctive characteristics in individual patients. Based on a
      better understanding of the natures of transitions from sinus rhythm to sudden
      cardiac and the mechanisms of arrhythmia prior to cardiac arrest, it should be
      possible to develop better methods for risk stratification.

PMID- 22144961
TI  - Heart rate variability - a historical perspective.
AB  - Heart rate variability (HRV), the beat-to-beat variation in either heart rate or
      the duration of the R-R interval - the heart period, has become a popular
      clinical and investigational tool. The temporal fluctuations in heart rate
      exhibit a marked synchrony with respiration (increasing during inspiration and
      decreasing during expiration - the so called respiratory sinus arrhythmia, RSA)
      and are widely believed to reflect changes in cardiac autonomic regulation.
      Although the exact contributions of the parasympathetic and the sympathetic
      divisions of the autonomic nervous system to this variability are controversial
      and remain the subject of active investigation and debate, a number of time and
      frequency domain techniques have been developed to provide insight into cardiac
      autonomic regulation in both health and disease. It is the purpose of this essay
      to provide an historical overview of the evolution in the concept of HRV.
      Briefly, pulse rate was first measured by ancient Greek physicians and
      scientists. However, it was not until the invention of the "Physician's Pulse
      Watch" (a watch with a second hand that could be stopped) in 1707 that changes in
      pulse rate could be accurately assessed. The Rev. Stephen Hales (1733) was the
      first to note that pulse varied with respiration and in 1847 Carl Ludwig was the
      first to record RSA. With the measurement of the ECG (1895) and advent of digital
      signal processing techniques in the 1960s, investigation of HRV and its
      relationship to health and disease has exploded. This essay will conclude with a
      brief description of time domain, frequency domain, and non-linear dynamic
      analysis techniques (and their limitations) that are commonly used to measure
      HRV.

PMID- 22144964
TI  - Application for proteomic techniques in studying osteoarthritis: a review.
AB  - After the genomic era, proteomic corresponds to a wide variety of techniques that
      study the protein content of cells, tissue, or organism and that allow the
      isolation of protein of interest. It offers the choice between gel-based and gel
      free methods or shotgun proteomics. Applications of proteomic technology may
      concern three principal objectives in several biomedical or clinical domains of
      research as in osteoarthritis: (i) to understand the physiopathology or
      underlying mechanisms leading to a disease or associated with a particular model,
      (ii), to find disease-specific biomarker, and (iii) to identify new therapeutic
      targets. This review aimed at gathering most of the data regarding the proteomic
      techniques and their applications to osteoarthritis research. It also reported
      technical limitations and solutions, as for example for sample preparation.
      Proteomics open wide perspectives in biochemical research but many technical
      matters still remain to be solved.

PMID- 22144965
TI  - Interactions between Controlled Atmospheres and Low Temperature Tolerance: A
      Review of Biochemical Mechanisms.
AB  - Controlled atmosphere treatments using carbon dioxide, oxygen, and/or nitrogen,
      together with controlled temperature and humidity, form an important method for
      post-harvest sterilization against insect-infested fruit. However, in insects,
      the cross tolerance and biochemical interactions between the various stresses of
      modified gas conditions and low temperature may either elicit or block standard
      stress responses which can potentiate (or limit) lethal low temperature exposure.
      Thus, the success of such treatments is sometimes erratic and does not always
      result in the desired pest mortality. This review focuses on the biochemical
      modes of action whereby controlled atmospheres affect insects low temperature
      tolerance, making them more (or occasionally, less) susceptible to cold
      sterilization. Insights into the integrated biochemical modes of action may be
      used together with the pests' low temperature tolerance physiology to determine
      which treatments may be of value in post-harvest sterilization.

PMID- 22144966
TI  - The dopamine hypothesis of drug addiction and its potential therapeutic value.
AB  - Dopamine (DA) transmission is deeply affected by drugs of abuse, and alterations
      in DA function are involved in the various phases of drug addiction and
      potentially exploitable therapeutically. In particular, basic studies have
      documented a reduction in the electrophysiological activity of DA neurons in
      alcohol, opiate, cannabinoid, and other drug-dependent rats. Further, DA release
      in the Nucleus accumbens (Nacc) is decreased in virtually all drug-dependent
      rodents. In parallel, these studies are supported by increments in intracranial
      self stimulation (ICSS) thresholds during withdrawal from alcohol, nicotine,
      opiates, and other drugs of abuse, thereby suggesting a hypofunction of the
      neural substrate of ICSS. Accordingly, morphological evaluations fed into
      realistic computational analysis of the medium spiny neuron of the Nacc, post
      synaptic counterpart of DA terminals, show profound changes in structure and
      function of the entire mesolimbic system. In line with these findings, human
      imaging studies have shown a reduction of dopamine receptors accompanied by a
      lesser release of endogenous DA in the ventral striatum of cocaine, heroin, and
      alcohol-dependent subjects, thereby offering visual proof of the "dopamine
      impoverished" addicted human brain. The lasting reduction in physiological
      activity of the DA system leads to the idea that an increment in its activity, to
      restore pre-drug levels, may yield significant clinical improvements (reduction
      of craving, relapse, and drug-seeking/taking). In theory, it may be achieved
      pharmacologically and/or with novel interventions such as transcranial magnetic
      stimulation (TMS). Its anatomo-physiological rationale as a possible therapeutic
      aid in alcoholics and other addicts will be described and proposed as a
      theoretical framework to be subjected to experimental testing in human addicts.

PMID- 22144968
TI  - A Functional MRI Study of Happy and Sad Emotions in Music with and without
      Lyrics.
AB  - Musical emotions, such as happiness and sadness, have been investigated using
      instrumental music devoid of linguistic content. However, pop and rock, the most
      common musical genres, utilize lyrics for conveying emotions. Using participants'
      self-selected musical excerpts, we studied their behavior and brain responses to
      elucidate how lyrics interact with musical emotion processing, as reflected by
      emotion recognition and activation of limbic areas involved in affective
      experience. We extracted samples from subjects' selections of sad and happy
      pieces and sorted them according to the presence of lyrics. Acoustic feature
      analysis showed that music with lyrics differed from music without lyrics in
      spectral centroid, a feature related to perceptual brightness, whereas sad music
      with lyrics did not diverge from happy music without lyrics, indicating the role
      of other factors in emotion classification. Behavioral ratings revealed that
      happy music without lyrics induced stronger positive emotions than happy music
      with lyrics. We also acquired functional magnetic resonance imaging data while
      subjects performed affective tasks regarding the music. First, using ecological
      and acoustically variable stimuli, we broadened previous findings about the brain
      processing of musical emotions and of songs versus instrumental music.
      Additionally, contrasts between sad music with versus without lyrics recruited
      the parahippocampal gyrus, the amygdala, the claustrum, the putamen, the
      precentral gyrus, the medial and inferior frontal gyri (including Broca's area),
      and the auditory cortex, while the reverse contrast produced no activations.
      Happy music without lyrics activated structures of the limbic system and the
      right pars opercularis of the inferior frontal gyrus, whereas auditory regions
      alone responded to happy music with lyrics. These findings point to the role of
      acoustic cues for the experience of happiness in music and to the importance of
      lyrics for sad musical emotions.

PMID- 22144967
TI  - Social behavior of offspring following prenatal cocaine exposure in rodents: a
      comparison with prenatal alcohol.
AB  - Clinical and experimental reports suggest that prenatal cocaine exposure (PCE)
      alters the offsprings' social interactions with caregivers and conspecifics.
      Children exposed to prenatal cocaine show deficits in caregiver attachment and
      play behavior. In animal models, a developmental pattern of effects that range
      from deficits in play and social interaction during adolescence, to aggressive
      reactions during competition in adulthood is seen. This review will focus
      primarily on the effects of PCE on social behaviors involving conspecifics in
      animal models. Social relationships are critical to the developing organism;
      maternally directed interactions are necessary for initial survival. Juvenile
      rats deprived of play behavior, one of the earliest forms of non-mother directed
      social behaviors in rodents, show deficits in learning tasks and sexual
      competence. Social behavior is inherently complex. Because the emergence of
      appropriate social skills involves the interplay between various conceptual and
      biological facets of behavior and social information, it may be a particularly
      sensitive measure of prenatal insult. The social behavior surveyed include social
      interactions, play behavior/fighting, scent marking, and aggressive behavior in
      the offspring, as well as aspects of maternal behavior. The goal is to determine
      if there is a consensus of results in the literature with respect to PCE and
      social behaviors, and to discuss discrepant findings in terms of exposure models,
      the paradigms, and dependent variables, as well as housing conditions, and the
      sex and age of the offspring at testing. As there is increasing evidence that
      deficits in social behavior may be sequelae of developmental exposure alcohol, we
      compare changes in social behaviors reported for prenatal alcohol with those
      reported for prenatal cocaine. Shortcomings in the both literatures are
      identified and addressed in an effort to improve the translational value of
      future experimentation.

PMID- 22144969
TI  - Effects of finger counting on numerical development - the opposing views of
      neurocognition and mathematics education.
AB  - Children typically learn basic numerical and arithmetic principles using finger
      based representations. However, whether or not reliance on finger-based
      representations is beneficial or detrimental is the subject of an ongoing debate
      between researchers in neurocognition and mathematics education. From the
      neurocognitive perspective, finger counting provides multisensory input, which
      conveys both cardinal and ordinal aspects of numbers. Recent data indicate that
      children with good finger-based numerical representations show better arithmetic
      skills and that training finger gnosis, or "finger sense," enhances mathematical
      skills. Therefore neurocognitive researchers conclude that elaborate finger-based
      numerical representations are beneficial for later numerical development.
      However, research in mathematics education recommends fostering mentally based
      numerical representations so as to induce children to abandon finger counting.
      More precisely, mathematics education recommends first using finger counting,
      then concrete structured representations and, finally, mental representations of
      numbers to perform numerical operations. Taken together, these results reveal an
      important debate between neurocognitive and mathematics education research
      concerning the benefits and detriments of finger-based strategies for numerical
      development. In the present review, the rationale of both lines of evidence will
      be discussed.

PMID- 22144970
TI  - "What am I Going to Say Here?" The Experiences of Doctors and Nurses
      Communicating with Patients in a Cancer Unit.
AB  - This paper describes a study investigating the provider-patient communication
      perceptions, experiences, needs, and strategies of doctors and nurses working
      together in a UK cancer setting. This was a qualitative study using individual
      interviews and focus group discussions. Interpretative phenomenological analysis
      was used to underpin data collection and analysis. Twenty-six staff participated
      in the project (18 nurses and 8 doctors). Both professional groups identified an
      inherent emotional strain in their daily interactions with patients. The
      strategies they adopted to reduce this strain fell into two main categories: (1)
      Handling or managing the patient to keep negative emotion at bay; and (2)
      Managing self to keep negative emotion at bay. These strategies allowed staff to
      maintain a sense of control in an emotionally stressful environment. Most
      believed that their communication skills were sufficient. In conclusion,
      communicating with and caring for cancer patients causes considerable
      psychosocial burden for doctors and nurses. Managing this burden influences their
      communication with patients. Without recognition of the need for staff to protect
      their own emotional well-being, communication skills training programs,
      emphasized in current UK cancer care guidelines, may have little impact on
      practice.

PMID- 22144971
TI  - The Role of Representations in Executive Function: Investigating a Developmental
      Link between Flexibility and Abstraction.
AB  - Young children often perseverate, engaging in previously correct, but no longer
      appropriate behaviors. One account posits that such perseveration results from
      the use of stimulus-specific representations of a situation, which are distinct
      from abstract, generalizable representations that support flexible behavior.
      Previous findings supported this account, demonstrating that only children who
      flexibly switch between rules could generalize their behavior to novel stimuli.
      However, this link between flexibility and generalization might reflect general
      cognitive abilities, or depend upon similarities across the measures or their
      temporal order. The current work examined these issues by testing the specificity
      and generality of this link. In two experiments with 3-year-old children,
      flexibility was measured in terms of switching between rules in a card-sorting
      task, while abstraction was measured in terms of selecting which stimulus did not
      belong in an odd-one-out task. The link between flexibility and abstraction was
      general across (1) abstraction dimensions similar to or different from those in
      the card-sorting task and (2) abstraction tasks that preceded or followed the
      switching task. Good performance on abstraction and flexibility measures did not
      extend to all cognitive tasks, including an IQ measure, and dissociated from
      children's ability to gaze at the correct stimulus in the odd-one-out task,
      suggesting that the link between flexibility and abstraction is specific to such
      measures, rather than reflecting general abilities that affect all tasks. We
      interpret these results in terms of the role that developing prefrontal cortical
      regions play in processes such as working memory, which can support both
      flexibility and abstraction.

PMID- 22144972
TI  - EEG Correlates of Song Prosody: A New Look at the Relationship between Linguistic
      and Musical Rhythm.
AB  - Song composers incorporate linguistic prosody into their music when setting words
      to melody, a process called "textsetting." Composers tend to align the expected
      stress of the lyrics with strong metrical positions in the music. The present
      study was designed to explore the idea that temporal alignment helps listeners to
      better understand song lyrics by directing listeners' attention to instances
      where strong syllables occur on strong beats. Three types of textsettings were
      created by aligning metronome clicks with all, some or none of the strong
      syllables in sung sentences. Electroencephalographic recordings were taken while
      participants listened to the sung sentences (primes) and performed a lexical
      decision task on subsequent words and pseudowords (targets, presented visually).
      Comparison of misaligned and well-aligned sentences showed that temporal
      alignment between strong/weak syllables and strong/weak musical beats were
      associated with modulations of induced beta and evoked gamma power, which have
      been shown to fluctuate with rhythmic expectancies. Furthermore, targets that
      followed well-aligned primes elicited greater induced alpha and beta activity,
      and better lexical decision task performance, compared with targets that followed
      misaligned and varied sentences. Overall, these findings suggest that alignment
      of linguistic stress and musical meter in song enhances musical beat tracking and
      comprehension of lyrics by synchronizing neural activity with strong syllables.
      This approach may begin to explain the mechanisms underlying the relationship
      between linguistic and musical rhythm in songs, and how rhythmic attending
      facilitates learning and recall of song lyrics. Moreover, the observations
      reported here coincide with a growing number of studies reporting interactions
      between the linguistic and musical dimensions of song, which likely stem from
      shared neural resources for processing music and speech.

PMID- 22144974
TI  - Commonalities between Perception and Cognition.
AB  - Perception and cognition are highly interrelated. Given the influence that these
      systems exert on one another, it is important to explain how perceptual
      representations and cognitive representations interact. In this paper, I analyze
      the similarities between visual perceptual representations and cognitive
      representations in terms of their structural properties and content.
      Specifically, I argue that the spatial structure underlying visual object
      representation displays systematicity - a property that is considered to be
      characteristic of propositional cognitive representations. To this end, I propose
      a logical characterization of visual feature binding as described by Treisman's
      Feature Integration Theory and argue that systematicity is not only a property of
      language-like representations, but also of spatially organized visual
      representations. Furthermore, I argue that if systematicity is taken to be a
      criterion to distinguish between conceptual and non-conceptual representations,
      then visual representations, that display systematicity, might count as an early
      type of conceptual representations. Showing these analogies between visual
      perception and cognition is an important step toward understanding the interface
      between the two systems. The ideas here presented might also set the stage for
      new empirical studies that directly compare binding (and other relational
      operations) in visual perception and higher cognition.

PMID- 22144975
TI  - Psychoanalytic treatment of psychological addiction to alcohol (alcohol abuse).
AB  - The DSM-V Committee plans to abolish the distinction between Alcohol Abuse and
      Alcohol Dependence (dsm5.org). The author presents a case report as a proof of
      concept that this distinction should be retained. The author has asserted that
      Alcohol Abuse is a purely psychological addiction, while Alcohol Dependence
      involves capture of the ventral tegmental dopaminergic SEEKING system (Johnson,
      2003). In psychological addiction the brain can be assumed to function normally,
      and ordinary psychoanalytic technique can be followed. For the patient described,
      transference interpretation was the fundamental key to recovery. Alcoholic
      drinking functioned to prevent this man from remembering overwhelming childhood
      events; events that were also lived out in his current relationships. Murders
      that occurred when he was a child were hidden in a screen memory. The patient had
      an obsessional style of relating where almost all feeling was left out of his
      associations. After he stopped drinking compulsively, he continued to work
      compulsively. The maternal transference had to be enacted and then interpreted in
      order for overwhelming memories to be allowed into conscious thought. After
      psychoanalysis, the patient resumed drinking and worked a normal schedule that
      allowed more fulfilling relationships. He had no further symptoms of distress
      from drinking over a 9-year followup. This case illustrates that Alcohol Abuse is
      a purely psychological illness, that it does not have the brain changes typical
      of Alcohol Dependence. Combining epidemiological, neurobiological, longitudinal,
      and psychoanalytic observations would allow multiple sources of information to be
      used in creating diagnostic categories. Losing details of human behavior by
      relying only on epidemiological studies is likely to cause errors in
      categorization of disorders. In turn, having faulty categories as the basis of
      further research is likely to impair identification of specific effective
      treatments.

PMID- 22144973
TI  - Riding the lexical speedway: a critical review on the time course of lexical
      selection in speech production.
AB  - Speech requires time. How much time often depends on the amount of labor the
      brain has to perform in order to retrieve the linguistic information related to
      the ideas we want to express. Although most psycholinguistic research in the
      field of language production has focused on the net result of time required to
      utter words in various experimental conditions, over the last years more and more
      researchers pursued the objective to flesh out the time course of particular
      stages implicated in language production. Here we critically review these
      studies, with particular interest for the time course of lexical selection.
      First, we evaluate the data underlying the estimates of an influential temporal
      meta-analysis on language production (Indefrey and Levelt, 2004). We conclude
      that those data alone are not sufficient to provide a reliable time frame of
      lexical selection. Next, we discuss recent neurophysiological evidence which we
      argue to offer more explicit insights into the time course of lexical selection.
      Based on this evidence we suggest that, despite the absence of a clear time frame
      of how long lexical selection takes, there is sufficient direct evidence to
      conclude that the brain initiates lexical access within 200 ms after stimulus
      presentation, hereby confirming Indefrey and Levelt's estimate. In a final
      section, we briefly review the proposed mechanisms which could lead to this rapid
      onset of lexical access, namely automatic spreading activation versus specific
      concept selection, and discuss novel data which support the notion of spreading
      activation, but indicate that the speed with which this principle takes effect is
      driven by a top-down signal in function of the intention to engage in a speech
      act.

PMID- 22144976
TI  - Obstructive sleep apnea in the formerly preterm infant: an overlooked diagnosis.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSA) is a frequent disorder in
      children. The clinical characteristics of OSA in very young children under 2
      years of age, and more particularly, in those born prematurely, and who have
      respiratory complications such as bronchopulmonary dysplasia (BPD), are not well
      defined. We therefore retrospectively reviewed our experience in a group of
      preterm infants with OSAS. METHODS: The records of premature infants with BPD
      followed in the Pediatric Pulmonary Clinic at the University of Chicago who were
      diagnosed with OSA from 2004 to 2009 were reviewed and analyzed. RESULTS: Twelve
      children, eight males, and four females with a mean gestational age of 27 weeks
      were found to have OSA. Mean age at diagnosis was 19 months. Inability to wean
      nighttime oxygen, the need to resume oxygen after intercurrent respiratory
      illness, and snoring were the most common presenting symptoms. The apnea-hypopnea
      index ranged from 1 to 120/h total sleep time (TST; mean: 29). SpO(2) nadir
      ranged from 50 to 91%. Despite adenotonsillectomy (AT), all children had
      persistent sleep disordered breathing. CONCLUSION: In preterm infants, while
      snoring is a frequent symptom, poor weight gain, and inability to wean nighttime
      oxygen may indicate the need for further investigation for OSA. In the former
      preterm infant structural changes in the airway may play an important role along
      with adenotonsillar hypertrophy. A high level of clinical awareness is required
      to identify OSA in the formerly preterm infant.

PMID- 22144977
TI  - Manipulating Immune Tolerance with Micro-RNA Regulated Gene Therapy.
AB  - The success of in vivo gene therapy greatly depends on the ability to control the
      immune response toward the therapeutic transgene. Over the last decade several
      vector-based and pharmacological approaches have been explored to control the
      immune-mediated clearance of transgene-expressing cells after viral delivery. One
      important outcome from these studies is the concept that expression of a
      transgene in tolerance-promoting organs, such as the liver and tolerogenic
      antigen-presenting cells, can help safeguard transgene-expressing cells from
      immune-mediated clearance. Gene therapists are now manipulating vectors to target
      naturally occurring tolerogenic properties of the body by: (i) incorporating
      tissue/cell specific promoters for targeted expression, (ii) using viral-capsid
      engineering to alter tropism and avoid pre-existing immunity, and (iii)
      regulating cell and activation dependent expression by including micro-RNA (miR)
      targets into expression cassettes. The combination of these three layers of
      vector regulation greatly enhances the targeting of tolerogenic cells and limits
      off-target expression of the transgene, which can lead to the induction of
      transgene-specific pathogenic effector T cells. In this review, we discuss the
      application of using miR transgene regulation to generate tolerogenic responses
      and speculate on possible mechanisms used by the liver to induce the transgene
      specific regulatory T cells.

PMID- 22144978
TI  - Food microbial biodiversity and "microbes of protected origin".

PMID- 22144979
TI  - The microbial sulfur cycle.

PMID- 22144980
TI  - A finite element mesh aggregating approach to multiple-source reconstruction in
      bioluminescence tomography.
AB  - A finite element mesh aggregating approach is presented to reconstruct images of
      multiple internal bioluminescence sources. Rather than assuming independence
      between mesh nodes, the proposed reconstruction strategy exploits spatial
      structure of nodes and aggregation feature of density distribution on the finite
      element mesh to adaptively determine the number of sources and to improve the
      quality of reconstructed images. With the proposed strategy integrated in the
      regularization-based reconstruction process, reconstruction algorithms need no a
      priori knowledge of source number; even more importantly, they can automatically
      reconstruct multiple sources that differ greatly in density or power.

PMID- 22144981
TI  - Protein surface characterization using an invariant descriptor.
AB  - Aim. To develop a new invariant descriptor for the characterization of protein
      surfaces, suitable for various analysis tasks, such as protein functional
      classification, and search and retrieval of protein surfaces over a large
      database. Methods. We start with a local descriptor of selected circular patches
      on the protein surface. The descriptor records the distance distribution between
      the central residue and the residues within the patch, keeping track of the
      number of particular pairwise residue cooccurrences in the patch. A global
      descriptor for the entire protein surface is then constructed by combining
      information from the local descriptors. Our method is novel in its focus on
      residue-specific distance distributions, and the use of residue-distance co
      occurrences as the basis for the proposed protein surface descriptors. Results.
      Results are presented for protein classification and for retrieval for three
      protein families. For the three families, we obtained an area under the curve for
      precision and recall ranging from 0.6494 (without residue co-occurrences) to
      0.6683 (with residue co-occurrences). Large-scale screening using two other
      protein families placed related family members at the top of the rank, with a
      number of uncharacterized proteins also retrieved. Comparative results with other
      proposed methods are included.

PMID- 22144982
TI  - Modulating the focus of attention for spoken words at encoding affects
      frontoparietal activation for incidental verbal memory.
AB  - Attention is crucial for encoding information into memory, and current dual
      process models seek to explain the roles of attention in both recollection memory
      and incidental-perceptual memory processes. The present study combined an
      incidental memory paradigm with event-related functional MRI to examine the
      effect of attention at encoding on the subsequent neural activation associated
      with unintended perceptual memory for spoken words. At encoding, we
      systematically varied attention levels as listeners heard a list of single
      English nouns. We then presented these words again in the context of a
      recognition task and assessed the effect of modulating attention at encoding on
      the BOLD responses to words that were either attended strongly, weakly, or not
      heard previously. MRI revealed activity in right-lateralized inferior parietal
      and prefrontal regions, and positive BOLD signals varied with the relative level
      of attention present at encoding. Temporal analysis of hemodynamic responses
      further showed that the time course of BOLD activity was modulated differentially
      by unintentionally encoded words compared to novel items. Our findings largely
      support current models of memory consolidation and retrieval, but they also
      provide fresh evidence for hemispheric differences and functional subdivisions in
      right frontoparietal attention networks that help shape auditory episodic recall.

PMID- 22144983
TI  - MRI texture analysis in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a complicated disease characterized by heterogeneous
      pathology that varies across individuals. Accurate identification and
      quantification of pathological changes may facilitate a better understanding of
      disease pathogenesis and progression and help identify novel therapies for MS
      patients. Texture analysis evaluates interpixel relationships that generate
      characteristic organizational patterns in an image, many of which are beyond the
      ability of visual perception. Given its promise detecting subtle structural
      alterations texture analysis may be an attractive means to evaluate disease
      activity and evolution. It may also become a new tool to assess therapeutic
      efficacy if technique issues are resolved and pathological correlates are further
      confirmed. This paper describes the concept, strategies, and considerations of
      MRI texture analysis; summarizes applications of texture analysis in MS as a
      measure of tissue integrity and its clinical relevance; then discusses
      potentially future directions of texture analysis in MS.

PMID- 22144984
TI  - Neural degeneration in the retina of the streptozotocin-induced type 1 diabetes
      model.
AB  - Diabetic retinopathy, a vision-threatening disease, has been regarded as a
      vascular disorder. However, impaired oscillatory potentials (OPs) in the
      electroretinogram (ERG) and visual dysfunction are recorded before severe
      vascular lesions appear. Here, we review the molecular mechanisms underlying the
      retinal neural degeneration observed in the streptozotocin-(STZ-) induced type 1
      diabetes model. The renin-angiotensin system (RAS) and reactive oxygen species
      (ROS) both cause OP impairment and reduced levels of synaptophysin, a synaptic
      vesicle protein for neurotransmitter release, most likely through excessive
      protein degradation by the ubiquitin-proteasome system. ROS also decrease brain
      derived neurotrophic factor (BDNF) and inner retinal neuronal cells. The
      influence of both RAS and ROS on synaptophysin suggests that RAS-ROS crosstalk
      occurs in the diabetic retina. Therefore, suppressors of RAS or ROS, such as
      angiotensin II type 1 receptor blockers or the antioxidant lutein, respectively,
      are potential candidates for neuroprotective and preventive therapies to improve
      the visual prognosis.

PMID- 22144985
TI  - Maternal diabetes in pregnancy: early and long-term outcomes on the offspring and
      the concept of "metabolic memory".
AB  - The adverse outcomes on the offspring from maternal diabetes in pregnancy are
      substantially documented. In this paper, we report main knowledge on impacts of
      maternal diabetes on early and long-term health of the offspring, with specific
      comments on maternal obesity. The main adverse outcome on progenies from
      pregnancy complicated with maternal diabetes appears to be macrosomia, as it is
      commonly known that intrauterine exposure to hyperglycemia increases the risk and
      programs the offspring to develop diabetes and/or obesity at adulthood. This
      "fetal programming", due to intrauterine diabetic milieu, is termed as "metabolic
      memory". In gestational diabetes as well as in macrosomia, the complications
      include metabolic abnormalities, degraded antioxidant status, disrupted immune
      system and potential metabolic syndrome in adult offspring. Furthermore, there is
      evidence that maternal obesity may also increase the risk of obesity and diabetes
      in offspring. However, women with GDM possibly exhibit greater macrosomia than
      obese women. Obesity and diabetes in pregnancy have independent and additive
      effects on obstetric complications, and both require proper management.
      Management of gestational diabetes mellitus and maternal obesity is essential for
      maternal and offspring's good health. Increasing physical activity, preventing
      gestational weight gain, and having some qualitative nutritional habits may be
      beneficial during both the pregnancy and offspring's future life.

PMID- 22144987
TI  - Cardiac function in 7-8-year-old offspring of women with type 1 diabetes.
AB  - Offspring of type 1 diabetic mothers (ODMs) are at risk of short-term and long
      term complications, such as neonatal macrosomia (birth weight >90th percentile),
      hypertrophic cardiomyopathy, and cardiovascular morbidity in later life. However,
      no studies have been performed regarding cardiac outcome. In this study, we
      investigated cardiac dimensions and function in 30 ODMs at 7-8 years of age in
      relation to neonatal macrosomia and maternal glycemic control during pregnancy
      and compared these with those in a control group of 30 children of nondiabetic
      women. We found that cardiac dimensions and systolic and diastolic function
      parameters in ODMs were comparable with those in controls. Neonatal macrosomia
      and poorer maternal glycemic control during pregnancy were not related to worse
      cardiac outcome in ODM. We conclude that cardiac function at 7-8 years of age in
      offspring of women with type 1 diabetes is reassuring and comparable with that in
      controls.

PMID- 22144988
TI  - Involvement of F-actin in chaperonin-containing t-complex 1 beta regulating mouse
      mesangial cell functions in a glucose-induction cell model.
AB  - The aim of this study is to investigate the role of chaperonin-containing t
      complex polypeptide 1 beta (CCT2) in the regulation of mouse mesangial cell (mMC)
      contraction, proliferation, and migration with filamentous/globular-(F/G-) actin
      ratio under high glucose induction. A low CCT2 mMC model induced by treatment of
      small interference RNA was established. Groups with and without low CCT2
      induction examined in normal and high (H) glucose conditions revealed the
      following major results: (1) low CCT2 or H glucose showed the ability to
      attenuate F/G-actin ratio; (2) groups with low F/G-actin ratio all showed less
      cell contraction; (3) suppression of CCT2 may reduce the proliferation and
      migration which were originally induced by H glucose. In conclusion, CCT2 can be
      used as a specific regulator for mMC contraction, proliferation, and migration
      affected by glucose, which mechanism may involve the alteration of F-actin,
      particularly for cell contraction.

PMID- 22144986
TI  - Fetoplacental vascular endothelial dysfunction as an early phenomenon in the
      programming of human adult diseases in subjects born from gestational diabetes
      mellitus or obesity in pregnancy.
AB  - Gestational diabetes mellitus (GDM) and obesity in pregnancy (OP) are
      pathological conditions associated with placenta vascular dysfunction coursing
      with metabolic changes at the fetoplacental microvascular and macrovascular
      endothelium. These alterations are seen as abnormal expression and activity of
      the cationic amino acid transporters and endothelial nitric oxide synthase
      isoform, that is, the "endothelial L-arginine/nitric oxide signalling pathway."
      Several studies suggest that the endogenous nucleoside adenosine along with
      insulin, and potentially arginases, are factors involved in GDM-, but much less
      information regards their role in OP-associated placental vascular alterations.
      There is convincing evidence that GDM and OP prone placental endothelium to an
      "altered metabolic state" leading to fetal programming evidenced at birth, a
      phenomenon associated with future development of chronic diseases. In this paper
      it is suggested that this pathological state could be considered as a metabolic
      marker that could predict occurrence of diseases in adulthood, such as
      cardiovascular disease, obesity, diabetes mellitus (including gestational
      diabetes), and metabolic syndrome.

PMID- 22144989
TI  - TRAIL and DcR1 expressions are differentially regulated in the pancreatic islets
      of STZ- versus CY-applied NOD mice.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is an important component of the
      immune system. Although it is well acknowledged that it also has an important
      role in Type 1 Diabetes (T1D) development, this presumed role has not yet been
      clearly revealed. Streptozotocin (STZ) and Cyclophosphamide (CY) are frequently
      used agents for establishment or acceleration of T1D disease in experimental
      models, including the non-obese diabetic (NOD) mice. Although such disease models
      are very suitable for diabetes research, different expression patterns for
      various T1D-related molecules may be expected, depending on the action mechanism
      of the applied agent. We accelerated diabetes in female NOD mice using STZ or CY
      and analyzed the expression profiles of TRAIL ligand and receptors throughout
      disease development. TRAIL ligand expression followed a completely different
      pattern in STZ- versus CY-accelerated disease, displaying a prominent increase in
      the former, while appearing at reduced levels in the latter. Decoy receptor 1
      (DcR1) expression also increased significantly in the pancreatic islets in STZ
      induced disease. Specific increases observed in TRAIL ligand and DcR1 expressions
      may be part of a defensive strategy of the beta islets against the infiltrating
      leukocytes, while the immune-suppressive agent CY may partly hold down this
      defense, contributing further to diabetes development.

PMID- 22144990
TI  - Phenotypic changes in diabetic neuropathy induced by a high-fat diet in diabetic
      C57BL/6 mice.
AB  - Emerging evidence suggests that dyslipidemia is an independent risk factor for
      diabetic neuropathy (DN) (reviewed by Vincent et al. 2009). To experimentally
      determine how dyslipidemia alters DN, we quantified neuropathic symptoms in
      diabetic mice fed a high-fat diet. Streptozotocin-induced diabetic C57BL/6 mice
      fed a high-fat diet developed dyslipidemia and a painful neuropathy (mechanical
      allodynia) instead of the insensate neuropathy (mechanical insensitivity) that
      normally develops in this strain. Nondiabetic mice fed a high-fat diet also
      developed dyslipidemia and mechanical allodynia. Thermal sensitivity was
      significantly reduced in diabetic compared to nondiabetic mice, but was not
      worsened by the high-fat diet. Moreover, diabetic mice fed a high-fat diet had
      significantly slower sensory and motor nerve conduction velocities compared to
      nondiabetic mice. Overall, dyslipidemia resulting from a high-fat diet may modify
      DN phenotypes and/or increase risk for developing DN. These results provide new
      insight as to how dyslipidemia may alter the development and phenotype of
      diabetic neuropathy.

PMID- 22144991
TI  - Angiotensin-converting enzyme genotype and peripheral arterial disease in
      diabetic patients.
AB  - We investigated the effect of traditional risk factors (hypertension,
      dyslipidemia and smoking) on the association between angiotensin-converting
      enzyme (ACE) gene insertion/deletion (I/D) polymorphism and peripheral arterial
      disease (PAD) in 945 (454 men and 491 women) Taiwanese type 2 diabetic patients
      with a mean age of 63.5 (SD: 11.4) years. Among them, 81 (31 men and 50 women)
      had PAD (ankle-brachial index <0.9). The adjusted odds ratios (95% confidence
      intervals) were 2.48 (1.18-5.21), 1.69 (1.00-2.85) and 1.64 (1.12-2.39),
      respectively, for recessive (DD versus II + ID), dominant (DD + ID versus II) and
      additive (II = 0, ID = 1 and DD = 2) models. While analyzing the interaction
      between DD and the individual risk factor of hypertension, smoking and
      dyslipidemia, patients with the risk factor and with DD had the highest risk
      compared to referent patients without the risk factor and with II/ID. The
      respective adjusted odds ratios were 5.41 (2.05-14.31), 7.38 (1.87-29.06) and
      4.64 (1.70-12.64). We did not find a significant interaction between DD and any
      of the risk factors under multiplicative or additive scale. In conclusion,
      traditional risk factors (hypertension, smoking and dyslipidemia) play an
      important role in the association between ACE genotypes and PAD. Patients with DD
      genotype and traditional risk factors are at the highest risk.

PMID- 22144994
TI  - Clostridium difficile Infection and Proton Pump Inhibitor Use in Hospitalized
      Pediatric Cystic Fibrosis Patients.
AB  - Children with cystic fibrosis (CF) often take proton pump inhibitors (PPIs),
      which helps improve efficacy of fat absorption with pancreatic enzyme replacement
      therapy. However, PPI use is known to be associated with Clostridium difficile
      (C. diff-) associated diarrhea (CDAD). We retrospectively evaluated the incidence
      of C. diff infection from all pediatric hospital admissions over a 5-year period
      at a single tertiary children's hospital. We found significantly more C. diff
      positive stool tests in hospitalized patients with CF compared to patients with
      no diagnosis of CF. However, use of a PPI was not associated with an increased
      risk of CDAD in hospitalized CF patients. In summary, C. diff infection is more
      common in hospitalized pediatric CF patients although PPI use may not be a risk
      factor for CDAD development in this patient population.

PMID- 22144993
TI  - Biologics in paediatric Crohn's disease.
AB  - Crohn's disease affects increasing numbers of children worldwide. Generally,
      childhood-onset disease runs a more severe course than in adults and has a
      greater impact on quality of life. Therapy in children must take account of a
      different set of risks for toxicity compared to adults, but also to their
      longevity. Biologic drugs present remarkable advantages in terms of disease
      control for children, especially in those whose disease cannot be controlled with
      conventional therapies, but their long-term risks are still being assessed. Data
      regarding biologic use in children is limited and mostly amounts to case series,
      but results have been promising, both in terms of controlling disease activity
      and improving growth parameters. Adverse reactions are infrequent in the short
      term, but loss of response is a long-term problem, particularly in children. More
      information is needed about very long term risks. Infliximab and adalimumab are
      the most studied agents in children, while there is relatively limited data on
      certolizumab and natalizumab. Further collection of data on these agents is still
      needed, but this should not restrict access to these agents for children in whom
      no other agent is effective.

PMID- 22144992
TI  - Endoplasmic reticulum stress and diabetic cardiomyopathy.
AB  - The endoplasmic reticulum (ER) is an organelle entrusted with lipid synthesis,
      calcium homeostasis, protein folding, and maturation. Perturbation of ER
      associated functions results in an evolutionarily conserved cell stress response,
      the unfolded protein response (UPR) that is also called ER stress. ER stress is
      aimed initially at compensating for damage but can eventually trigger cell death
      if ER stress is excessive or prolonged. Now the ER stress has been associated
      with numerous diseases. For instance, our recent studies have demonstrated the
      important role of ER stress in diabetes-induced cardiac cell death. It is known
      that apoptosis has been considered to play a critical role in diabetic
      cardiomyopathy. Therefore, this paper will summarize the information from the
      literature and our own studies to focus on the pathological role of ER stress in
      the development of diabetic cardiomyopathy. Improved understanding of the
      molecular mechanisms underlying UPR activation and ER-initiated apoptosis in
      diabetic cardiomyopathy will provide us with new targets for drug discovery and
      therapeutic intervention.

PMID- 22144995
TI  - Model for Electrical Field Distribution in the Human Esophagus during Stimulation
      with Patch and Ring Electrodes.
AB  - Introduction. Electrical stimulation is used in experimental human pain models.
      The aim was to develop a model that visualizes the distribution of electrical
      field in the esophagus close to ring and patch electrodes mounted on an
      esophageal catheter and to explain the obtained sensory responses. Methods.
      Electrical field distribution in esophageal layers (mucosa, muscle layers, and
      surrounding tissue) was computed using a finite element model based on a 3D
      model. Each layer was assigned different electrical properties. An electrical
      field exceeding 20 V/m was considered to activate the esophageal afferents.
      Results. The model output showed homogeneous and symmetrical field surrounding
      ring electrodes compared to a saddle-shaped field around patch electrodes.
      Increasing interelectrode distance enlarged the electrical field in muscle layer.
      Conclusion. Ring electrodes with 10 mm interelectrode distance seem optimal for
      future catheter designs. Though the model needs further validation, the results
      seem useful for electrode designs and understanding of electrical stimulation
      patterns.

PMID- 22144996
TI  - Prevalence and risk factors of gastrointestinal disorders in patients with
      rheumatoid arthritis: results from a population-based survey in olmsted county,
      Minnesota.
AB  - Objectives. To compare the prevalence of gastrointestinal (GI) disorders in
      rheumatoid arthritis (RA) versus non-RA subjects and to describe determinants of
      GI disorders in RA. Methods. The bowel disease questionnaire was completed by RA
      and non-RA subjects. RA patients also completed the health assessment
      questionnaire (HAQ). Results. The study responders included 284 RA and 233 non-RA
      subjects. Abdominal pain/discomfort, postprandial fullness, nausea, and stool
      leakage were significantly more common in RA versus non-RA (odds ratios [OR] =
      1.8; 1.9; 4.0; 8.2, resp.). The use of laxatives, proton pump inhibitors, NSAIDs,
      acetaminophen, and narcotics was more commonly reported in RA versus non-RA (OR =
      2.0; 1.7; 3.0; 2.0; 1.9, resp.). Age < 60 and HAQ >= 1 were associated with
      dyspepsia, irritable bowel syndrome, gastroesophageal reflux disease, and GI
      symptom complex overlap in RA. Conclusion. Several upper and lower GI disorders
      were significantly more prevalent in RA versus non-RA subjects. Age <60 and
      physical function impairment (HAQ >= 1) were associated with GI disorders in RA.

PMID- 22144997
TI  - Radiation proctitis: current strategies in management.
AB  - Radiation proctitis is a known complication following radiation therapy for
      pelvic malignancy. The majority of cases are treated nonsurgically, and an
      understanding of the available modalities is crucial in the management of these
      patients. In this paper, we focus on the current treatments of radiation
      proctitis.

PMID- 22144998
TI  - Advanced endoscopic imaging for diagnosis of Crohn's disease.
AB  - Endoscopy in IBD has tremendous importance to diagnose inflammatory activity, to
      evaluate therapeutic success and for the surveillance of colitis associated
      cancer. Thus it becomes obvious that there is a need for new and more advanced
      endoscopic imaging techniques for better characterization of mucosal inflammation
      and early neoplasia detection in IBD. This paper describes the concept of
      advanced endoscopic imaging for the diagnosis and characterization of Crohn's
      disease, including magnification endoscopy, chromoendoscopy, balloon-assisted
      enteroscopy, capsule endoscopy, confocal laser endomicroscopy, and endocytoscopy.

PMID- 22144999
TI  - An assessment of the cariogenicity of commonly used infant milk formulae using
      microbiological and biochemical methods.
AB  - Dental caries is an important dental public health problem and is the most
      prevalent oral disease among children in the world. The present study was
      undertaken to evaluate and comparatively assess the change in plaque and salivary
      pH after ingestion of various commercially available infant milk formulae, and
      also to evaluate and comparatively assess plaque and salivary samples for change
      in colony-forming units of Streptococcus mutans caused due to their ingestion. 36
      children in the age group of 1-2 years were fed with infant milk formulae three
      times a day for 21 days and results quantified. The present study revealed a
      highly significant increase in the levels of colony-forming units of
      Streptococcus mutans in both the plaque and salivary samples when assessed at
      baseline and after a period of 21 days, with the t value being 11.92 for the
      plaque samples and 11.66 for the salivary samples. It was also observed that all
      the test samples produced significantly lower plaque pH values than pre-feed pH.
      Based upon this study, further evaluation of the cariogenicity of infant milk
      formulae is recommended.

PMID- 22145000
TI  - Frequency of dental caries in four historical populations from the chalcolithic
      to the middle ages.
AB  - The majority of dental carie studies over the course of historical period
      underline mainly the prevalence evolution, the role of carbohydrates consumption
      and the impact of access to dietary resources. The purpose of the present
      investigation was to compare population samples from two archaeological periods
      the Chacolithic and Middle Age taking into account the geographical and socio
      economical situation. The study concerned four archaelogical sites in south west
      France and population samples an inlander for the Chalcolithic Age, an inlander,
      an costal and urban for the Middle Age. The materials studied included a total of
      127 maxillaries, 103 mandibles and 3316 teeth. Data recorded allowed us to
      display that the Chalcolithic population sample had the lowest carie percentage
      and the rural inlander population samples of Middle Age the highest; in all cases
      molars were teeth most often affected. These ones differences could be explained
      according to time period, carious lesions were usually less recorded in the
      Chalcolithic Age than the Middle because of a lesser cultivation of cereals like
      in les Treilles Chacolithic population sample. In the Middle Age population
      samples, the rural inland sample Marsan showed the highest frequency of caries
      and ate more cereal than the coastal Vilarnau and the poor urban St Michel
      population samples, the first one ate fish and Mediterranean vegetal and fruits
      and the second one met difficulties to food access, in both cases the consumption
      of carbohydrates was lesser than Marsan population sample who lived in a
      geographical land convice to cereals cultivation.

PMID- 22145001
TI  - Removal of gutta-percha/zinc-oxide-eugenol sealer or gutta-percha/epoxy resin
      sealer from severely curved canals: an in vitro study.
AB  - The aim of this study was to compare the cleanliness of root canal walls after
      retreatment using two rotary retreatment files to hand instruments in severely
      curved canals obturated with gutta-percha and two different sealers. Single
      rooted mandibular premolars (n = 90) with root curvatures were instrumented and
      obturated with gutta-percha and an epoxy resin (Group 1, n = 45) or zinc oxide
      eugenol sealer (Group 2, n = 45). Following retreatment of the specimens (n = 15
      ProTaper Universal Retreatment Files (Subgroup B) or R-Endo retreatment files
      (Subgroup C) after 1 month, split specimens were examined under a
      stereomicroscope and the percentage of remaining root filling material was
      statistically compared using one way ANOVA with Bonferroni adjustment for
      multiple comparisons (P = 0.05). The R-Endo system performed significantly better
      than the other two file systems (P < 0.05). None of the systems used in this
      study cleaned root canals thoroughly. The R-Endo system did provide cleaner walls
      when compared to the other instruments used. The type of root filling materials
      had an impact on the outcomes with all techniques.

PMID- 22145002
TI  - A randomized controlled trail comparing the efficacy of 0.5% centbucridine to 2%
      lignocaine as local anesthetics in dental extractions.
AB  - The development of local anesthesia in dentistry has marked the beginning of a
      new era in terms of pain control. Lignocaine is the most commonly used local
      anesthetic (LA) agent even though it has a vasodilative effect and needs to be
      combined with adrenaline. Centbucridine is a non-ester, non amide group LA and
      has not been comprehensively studied in the dental setting and the objective was
      to compare it to Lignocaine. This was a randomized study comparing the onset
      time, duration, depth and cardiovascular parameters between Centbucridine (0.5%)
      and Lignocaine (2%). The study was conducted in the dental outpatient department
      at the Government Dental College in India on patients attending for the
      extraction of lower molars. A total of 198 patients were included and there were
      no significant differences between the LAs except those who received
      Centbucridine reported a significantly longer duration of anesthesia compared to
      those who received Lignocaine. None of the patients reported any side effects.
      Centbucridine was well tolerated and its substantial duration of anesthesia could
      be attributed to its chemical compound. Centbucridine can be used for dental
      procedures and can confidently be used in patients who cannot tolerate Lignocaine
      or where adrenaline is contraindicated.

PMID- 22145003
TI  - Oral health knowledge and practices of secondary school students, tanga,
      Tanzania.
AB  - A good quality of life is possible if students maintain their oral health and
      become free of oral disease. A structured questionnaire assessed 785 students'
      level of oral health knowledge and practices. About 694 (88.4%) students had
      adequate level of knowledge on causes, prevention, and signs of dental caries,
      760 (96.8%) on causes and prevention of periodontal diseases, 695 (88.5%) on
      cigarette smoking as cause of oral cancer, and 770 (98.1%) students on importance
      of dental checkups. Majority 717 (91.3%) had adequate practice of sugary food
      consumption; while 568 (72.4%) had acceptable frequency of tooth brushing, 19
      (2.4%) brushed at an interval of twelve hours, and 313 (39.9%) visited for
      checkup. Majority of students had an adequate level of knowledge on oral health
      but low level of oral health practices. Both genders had similar level of
      knowledge with male predominance in oral health practices. Age had no influence
      on the level of oral health knowledge and practices of students.

PMID- 22145004
TI  - Number of natural teeth and oral impacts: a study on sri lankan adults.
AB  - The aim of the study was to determine the association between the number of
      natural teeth and oral impacts in Sri Lankan adults. The sample consisted of 476,
      40-59 and 452, >=60 year olds. Oral impacts were assessed using a validated
      Sinhalese translation of the Oral Health Impact Profile-14 scale. A receiver
      operating characteristic (ROC) curve was plotted to determine the number of
      natural teeth that would best discriminate those with oral impacts from those
      without. Oral impacts were reported by 26% of the 40-59 year olds and 34% of the
      older individuals. In both groups there was a significant negative correlation
      between the number of teeth present and oral impacts. The ROC curve for the 40-59
      year olds gave an area under the curve (AUC) of 0.758 (95% CI = 0.702-0.814; P <
      0.001) with an optimal cut-off of 24/25 teeth while for the >=60 year olds, the
      AUC of the ROC curve was 0.737 (95% CI = 0.684-0.790; P < 0.001) with an optimal
      cut-off of 18/19 teeth. Based on the ROC curves the optimal cutoffs of the number
      of natural teeth that best discriminated between those with and without oral
      impacts for 40-59 and >=60 year olds were 24-25 and 18-19, respectively.

PMID- 22145005
TI  - Keratinized Gingiva Determines a Homeostatic Behavior of Gingival Sulcus through
      Transudation of Gingival Crevice Fluid.
AB  - Objective. To shed light on the role of KG, its influence on periodontal behavior
      was investigated. Methods. Tissue fluid transudation was assessed in alveolar
      mucosa (P1A), outer gingival margin (P1B), at entrance of (P2) and within
      gingival sulcus (P3), before and after chewing of fibrous food in 16 patients
      portraying >=2 mm KG at one tooth (group 1), and <2 mm at another homologous
      tooth (group 2). Results. There was a significant increase in GCF after chewing
      at P1B and P3 in group 1 and at P1A in group 2 (t-test, P < 0.05). Conclusions.
      The results suggest that KG plays a role in marginal periodontal homeostasis.

PMID- 22145006
TI  - Biocompatibility of dental amalgams.
AB  - Objective. The purpose of this review paper is to review the literature regarding
      the toxicology of mercury from dental amalgam and evaluate current statements on
      dental amalgam. Materials and Methods. Two key-words "dental amalgam" and
      "toxicity" were used to search publications on dental amalgam biocompatibility
      published in peer-reviewed journals written in English. Manual search was also
      conducted. The most recent declarations and statements were evaluated using
      information available on the internet. Case reports were excluded from the study.
      Results. The literature show that mercury released from dental amalgam
      restorations does not contribute to systemic disease or systemic toxicological
      effects. No significant effects on the immune system have been demonstrated with
      the amounts of mercury released from dental amalgam restorations. Only very
      rarely have there been reported allergic reactions to mercury from amalgam
      restorations. No evidence supports a relationship between mercury released from
      dental amalgam and neurological diseases. Almost all of the declarations accessed
      by the internet stated by official organizations concluded that current data are
      not sufficient to relate various complaints and mercury release from dental
      amalgam. Conclusions. Available scientific data do not justify the
      discontinuation of amalgam use from dental practice or replacement with
      alternative restorative dental materials.

PMID- 22145007
TI  - HIC-5: A Mobile Molecular Scaffold Regulating the Anchorage Dependence of Cell
      Growth.
AB  - HIC-5 is a multidomain LIM protein homologous to paxillin that serves as a
      molecular scaffold at focal adhesions and in the nucleus. It forms mobile
      molecular units with LIM-only proteins, PINCH, and CRP2 and translocates in and
      out of the nucleus via a nuclear export signal (NES). Of note, NES of HIC-5 is
      distinctive in its sensitivity to the cellular redox state. Recently, the mobile
      units of HIC-5 have been suggested to be involved in the regulation of the
      anchorage dependence of cell growth. On loss of adhesion, an increase in reactive
      oxygen species in the cells modifies NES and stops shuttling, which leads to cell
      cycle control. More specifically, the system circumvents nuclear localization of
      cyclin D1 and transactivates p21(Cip1) in detached cells, thereby avoiding
      anchorage-independent cell growth. Thus, the HIC-5-LIM only protein complex has
      emerged as a fail-safe system for regulating the anchorage dependence of cell
      growth.

PMID- 22145008
TI  - Utility of on-site evaluation of endobronchial ultrasound-guided transbronchial
      needle aspiration specimens.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is an integral tool in the diagnosis and staging of malignant tumors
      of the lung. Rapid on-site evaluation (ROSE) of fine needle aspiration (FNA)
      samples has been advocated for as a guide for assessing the accuracy and adequacy
      of biopsy samples. Although ROSE has proven useful for numerous sites and
      procedures, few studies have specifically investigated its utility in the
      assessment of EBUS-TBNA specimens. The intention of this study was to explore the
      utility of ROSE for EBUS-TBNA specimens. MATERIALS AND METHODS: The pathology
      files at our institution were searched for all EBUS-TBNA cases performed between
      January 2010 and June 2010. The data points included number of sites sampled per
      patient, location of site(s) sampled, on-site evaluation performed, preliminary
      on-site diagnosis rendered, final cytologic diagnosis, surgical pathology follow
      up, cell blocks, and ancillary studies performed. RESULTS: A total of 294 EBUS
      TBNA specimens were reviewed and included in the study; 264 of 294 (90%) were
      lymph nodes and 30 of 294 (10%) were lung mass lesions. ROSE was performed for
      140 of 294 (48%) specimens. The on-site and final diagnoses were concordant in
      104 (74%) and discordant in 36 (26%) cases. Diagnostic specimens were obtained in
      132 of 140 (94%) cases with on-site evaluation and 138 of 154 (90%) without on
      site evaluation. The final cytologic diagnosis was malignant in 60 of 132 (45%)
      cases with ROSE and 46 of 138 (33%) cases without ROSE, and the final diagnosis
      was benign in 57 of 132 (47%) with ROSE and 82 of 138 (59%) without ROSE. A cell
      block was obtained in 129 of 140 (92%) cases with ROSE and 136 of 154 (88%) cases
      without ROSE. CONCLUSIONS: The data demonstrate no remarkable difference in
      diagnostic yield, the number of sites sampled per patient, or clinical decision
      making between specimens collected via EBUS-TBNA with or without ROSE. As a
      result, this study challenges the notion that ROSE is beneficial for the
      evaluation of EBUS-TBNA specimens.

PMID- 22145009
TI  - Cytological analysis of small branch-duct intraductal papillary mucinous
      neoplasms provides a more accurate risk assessment of malignancy than symptoms.
AB  - OBJECTIVES: The Sendai guidelines for management of patients with clinically
      suspected intraductal papillary mucinous neoplasms (IPMN) recommend resection of
      cysts > 30 mm, a dilated main pancreatic duct (MPD) > 6 mm, a mural nodule (MN),
      symptoms or positive cytology. Although sensitive, asymptomatic cysts,
      nonspecific symptoms, and a high threshold for positive cytology limit the
      specificity of the guidelines. We have assessed the value of cytology relative to
      symptom for predicting malignancy in IPMNs without high-risk imaging features.
      MATERIALS AND METHODS: We retrospectively reviewed the clinical, radiological,
      and cytological data of 31 small branch-duct IPMNs without a MN. The cytological
      presence of high-grade atypical epithelial cells (HGA) was considered true
      positive, with a corresponding histology of high-grade dysplasia or invasive
      carcinoma. The performance of cytology versus symptoms was evaluated by
      calculating the sensitivity, specificity, negative predictive value (NPV),
      positive predictive value (PPV), and accuracy. RESULTS: The sensitivity (0.80),
      specificity (0.85), and accuracy (0.84) of HGA were higher than the corresponding
      performance characteristics of symptoms (0.60, 0.45, and 0.48, respectively). The
      NPV of no HGA on cytology was > 95%. CONCLUSIONS: Cytology is a better predictor
      of malignancy than symptoms, for the conservative management of small branch-duct
      IPMNs. Cytology contributes to a highly accurate triple negative test for
      malignancy in small IPMN: No dilated MPD, MN or HGA.

PMID- 22145010
TI  - Optical tweezers study life under tension.
AB  - Optical tweezers have become one of the primary weapons in the arsenal of
      biophysicists, and have revolutionized the new field of single-molecule
      biophysics. Today's techniques allow high-resolution experiments on biological
      macromolecules that were mere pipe dreams only a decade ago.

PMID- 22145011
TI  - Investigation of peri-implant bone healing using autologous plasma rich in growth
      factors in the canine mandible after 12 weeks: a pilot study.
AB  - INTRODUCTION: Faster reconstruction of patients' masticatory systems is the aim
      of modern dentistry. A number of studies have indicated that application of
      growth factors to the surface of a dental implant leads to accelerated and
      enhanced osseointegration. The objective of the present study was to investigate
      the effect of plasma rich in growth factors on peri-implant bone healing.
      MATERIALS AND METHODS: For the purpose of this study, two healthy, mixed-breed
      canines were selected, and the premolars were extracted from both sides of the
      mandible. Three months after premolar removal, 12 implants, each 5 mm in diameter
      and 10 mm in length, were placed in osteotomy sites on both sides of the
      mandible. Prior to placement, plasma rich in growth factors was applied to the
      surfaces of six implants, while the other six were used without plasma rich in
      growth factors. The implants were removed after 12 weeks along with the bone
      surrounding the sites using a trephine bur. One mesiodistal section containing
      the surrounding bone from each implant block, 50 um in diameter, was prepared for
      histologic and histomorphometric investigation with an optical microscope.
      RESULTS: The sites with implants treated with plasma rich in growth factors
      showed more bone-to-implant contact compared to control sites. Also, higher
      values for bone trabecular thickness and bone maturity were recorded for the PRGF
      treated sites than for the control sites. CONCLUSION: Application of plasma rich
      in growth factors to the surface of an implant may enhance the bone healing
      process as well as bone-to-implant contact, thereby helping to achieve faster
      osseointegration.

PMID- 22145012
TI  - Appearance of Klebsiella pneumoniae liver abscess syndrome in Argentina: case
      report and review of molecular mechanisms of pathogenesis.
AB  - Klebsiella pneumoniae liver abscess syndrome (KLAS) is an emerging invasive
      infection caused by highly virulent community-acquired strains of K. pneumoniae
      displaying hypermucoviscosity. The salient features of this syndrome include the
      presence of bacteremia, primary monomicrobial liver abscess, and metastatic
      complications. A previously healthy Argentinean man presented with fever and
      found to have liver abscess caused by K. pneumoniae with metastatic seeding of
      gastric wall. Cultures from blood and liver abscess grew hypermucoviscous K1 K.
      pneumoniae with sequence type (ST) 23 by multilocus sequence typing (MLST),
      positive for rmpA (regulator of mucoid phenotype A), wzy(KpK1) (capsular
      polymerase) and aerobactin genes. The hypermucoviscous phenotype of this K.
      pneumoniae isolate was readily identified by the "string test" (colonies formed a
      long string when touched with a loop). The patient responded favourably to
      percutaneous drainage of the abscess and antibiotics. This is the first
      documented report of KLAS described in Argentina, and may signal the emergence of
      this syndrome in South America.

PMID- 22145013
TI  - Drug discovery toward antagonists of methyl-lysine binding proteins.
AB  - The recognition of methyl-lysine and -arginine residues on both histone and other
      proteins by specific "reader" elements is important for chromatin regulation,
      gene expression, and control of cell-cycle progression. Recently the crucial role
      of these reader proteins in cancer development and dedifferentiation has emerged,
      owing to the increased interest among the scientific community. The methyl-lysine
      and -arginine readers are a large and very diverse set of effector proteins and
      targeting them with small molecule probes in drug discovery will inevitably
      require a detailed understanding of their structural biology and mechanism of
      binding. In the following review, the critical elements of methyl-lysine and 
      arginine recognition will be summarized with respect to each protein family and
      initial results in assay development, probe design, and drug discovery will be
      highlighted.

PMID- 22145018
TI  - Chemotaxis in densely populated tissue determines germinal center anatomy and
      cell motility: a new paradigm for the development of complex tissues.
AB  - Germinal centers (GCs) are complex dynamic structures that form within lymph
      nodes as an essential process in the humoral immune response. They represent a
      paradigm for studying the regulation of cell movement in the development of
      complex anatomical structures. We have developed a simulation of a modified
      cyclic re-entry model of GC dynamics which successfully employs chemotaxis to
      recapitulate the anatomy of the primary follicle and the development of a mature
      GC, including correctly structured mantle, dark and light zones. We then show
      that correct single cell movement dynamics (including persistent random walk and
      inter-zonal crossing) arise from this simulation as purely emergent properties.
      The major insight of our study is that chemotaxis can only achieve this when
      constrained by the known biological properties that cells are incompressible,
      exist in a densely packed environment, and must therefore compete for space. It
      is this interplay of chemotaxis and competition for limited space that generates
      all the complex and biologically accurate behaviors described here. Thus, from a
      single simple mechanism that is well documented in the biological literature, we
      can explain both higher level structure and single cell movement behaviors. To
      our knowledge this is the first GC model that is able to recapitulate both
      correctly detailed anatomy and single cell movement. This mechanism may have wide
      application for modeling other biological systems where cells undergo complex
      patterns of movement to produce defined anatomical structures with sharp tissue
      boundaries.

PMID- 22145019
TI  - Localization of ASV integrase-DNA contacts by site-directed crosslinking and
      their structural analysis.
AB  - BACKGROUND: We applied crosslinking techniques as a first step in preparation of
      stable avian sarcoma virus (ASV) integrase (IN)-DNA complexes for
      crystallographic investigations. These results were then compared with the
      crystal structures of the prototype foamy virus (PFV) intasome and with published
      data for other retroviral IN proteins. METHODOLOGY/RESULTS: Photoaffinity
      crosslinking and site-directed chemical crosslinking were used to localize the
      sites of contacts with DNA substrates on the surface of ASV IN. Sulfhydryl groups
      of cysteines engineered into ASV IN and amino-modified nucleotides in DNA
      substrates were used for attachment of photocrosslinkers. Analysis of
      photocrosslinking data revealed several specific DNA-protein contacts. To confirm
      contact sites, thiol-modified nucleotides were introduced into oligo-DNA
      substrates at suggested points of contact and chemically crosslinked to the
      cysteines via formation of disulfide bridges. Cysteines incorporated in positions
      124 and 146 in the ASV IN core domain were shown to interact directly with host
      and viral portions of the Y-mer DNA substrate, respectively. Crosslinking of an
      R244C ASV IN derivative identified contacts at positions 11 and 12 on both
      strands of viral DNA. The most efficient disulfide crosslinking was observed for
      complexes of the ASV IN E157C and D64C derivatives with linear viral DNA
      substrate carrying a thiol-modified scissile phosphate. CONCLUSION: Analysis of
      our crosslinking results as well as published results of retroviral IN protein
      from other laboratories shows good agreement with the structure of PFV IN and
      derived ASV, HIV, and MuLV models for the core domain, but only partial agreement
      for the N- and C-terminal domains. These differences might be explained by
      structural variations and evolutionary selection for residues at alternate
      positions to perform analogous functions, and by methodological differences:
      i.e., a static picture of a particular assembly from crystallography vs. a
      variety of interactions that might occur during formation of functional IN
      complexes in solution.

PMID- 22145020
TI  - Drosophila Dynein intermediate chain gene, Dic61B, is required for
      spermatogenesis.
AB  - This study reports the identification and characterization of a novel gene,
      Dic61B, required for male fertility in Drosophila. Complementation mapping of a
      novel male sterile mutation, ms21, isolated in our lab revealed it to be allelic
      to CG7051 at 61B1 cytogenetic region, since two piggyBac insertion alleles,
      CG7051(c05439) and CG7051(f07138) failed to complement. CG7051 putatively encodes
      a Dynein intermediate chain. All three mutants, ms21, CG7051(c05439) and
      CG7051(f07138), exhibited absolute recessive male sterility with abnormally
      coiled sperm axonemes causing faulty sperm individualization as revealed by
      Phalloidin staining in Don Juan-GFP background. Sequencing of PCR amplicons
      uncovered two point mutations in ms21 allele and confirmed the piggyBac
      insertions in CG7051(c05439) and CG7051(f07138) alleles to be in 5'UTR and 4(th)
      exon of CG7051 respectively, excision of which reverted the male sterility. In
      situ hybridization to polytene chromosomes demonstrated CG7051 to be a single
      copy gene. RT-PCR of testis RNA revealed defective splicing of the CG7051
      transcripts in mutants. Interestingly, expression of cytoplasmic dynein
      intermediate chain, alpha, beta, gamma tubulins and alpha-spectrin was normal in
      mutants while ultra structural studies revealed defects in the assembly of sperm
      axonemes. Bioinformatics further highlighted the homology of CG7051 to axonemal
      dynein intermediate chain of various organisms, including DNAI1 of humans,
      mutations in which lead to male sterility due to immotile sperms. Based on these
      observations we conclude that CG7051 encodes a novel axonemal dynein intermediate
      chain essential for male fertility in Drosophila and rename it as Dic61B. This is
      the first axonemal Dic gene of Drosophila to be characterized at molecular level
      and shown to be required for spermatogenesis.

PMID- 22145022
TI  - Ambulatory multi-drug resistant tuberculosis treatment outcomes in a cohort of
      HIV-infected patients in a slum setting in Mumbai, India.
AB  - BACKGROUND: India carries one quarter of the global burden of multi-drug
      resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV.
      Despite this reality, provision of treatment for MDR-TB is extremely limited,
      particularly for HIV-infected individuals. Medecins Sans Frontieres (MSF) has
      been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the
      first report of treatment outcomes among HIV-infected MDR-TB patients in India.
      METHODS: HIV-infected patients with suspected MDR-TB were referred to the MSF
      clinic by public Antiretroviral Therapy (ART) Centers or by a network of
      community non-governmental organizations. Patients were initiated on either
      empiric or individualized second-line TB-treatment as per WHO recommendations.
      MDR-TB treatment was given on an ambulatory basis and under directly observed
      therapy using a decentralized network of providers. Patients not already
      receiving ART were started on treatment within two months of initiating MDR-TB
      treatment. RESULTS: Between May 2007 and May 2011, 71 HIV-infected patients were
      suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was
      confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final
      treatment outcomes were available for 23 patients; 11 (48%) were successfully
      treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall,
      among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%)
      died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and
      still on treatment at the end of the observation period. Twenty-six patients
      (45%) experienced moderate to severe adverse events, requiring modification of
      the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died,
      including 7 not initiated on treatment. CONCLUSIONS: Despite high fluoroquinolone
      resistance and extensive prior second-line treatment, encouraging results are
      being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid
      scale-up of both ART and second-line treatment for MDR-TB is needed to ensure
      survival of co-infected patients and mitigate this growing epidemic.

PMID- 22145021
TI  - Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein
      staining and endotoxin exposure markers in early Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder of
      aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies
      whose main component is alpha-synuclein protein. The finding of these Lewy bodies
      in the intestinal enteric nerves led to the hypothesis that the intestine might
      be an early site of PD disease in response to an environmental toxin or pathogen.
      One potential mechanism for environmental toxin(s) and proinflammatory luminal
      products to gain access to mucosal neuronal tissue and promote oxidative stress
      is compromised intestinal barrier integrity. However, the role of intestinal
      permeability in PD has never been tested. We hypothesized that PD subjects might
      exhibit increased intestinal permeability to proinflammatory bacterial products
      in the intestine. To test our hypothesis we evaluated intestinal permeability in
      subjects newly diagnosed with PD and compared their values to healthy subjects.
      In addition, we obtained intestinal biopsies from both groups and used
      immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative
      stress), and alpha-synuclein. We also evaluated serum markers of endotoxin
      exposure including LPS binding protein (LBP). Our data show that our PD subjects
      exhibit significantly greater intestinal permeability (gut leakiness) than
      controls. In addition, this intestinal hyperpermeability significantly correlated
      with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine,
      and alpha-synuclein as well as serum LBP levels in PD subjects. These data
      represent not only the first demonstration of abnormal intestinal permeability in
      PD subjects but also the first correlation of increased intestinal permeability
      in PD with intestinal alpha-synuclein (the hallmark of PD), as well as staining
      for gram negative bacteria and tissue oxidative stress. Our study may thus shed
      new light on PD pathogenesis as well as provide a new method for earlier
      diagnosis of PD and suggests potential therapeutic targets in PD subjects. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01155492.

PMID- 22145023
TI  - Performance of the QuickVue Influenza A+B rapid test for pandemic H1N1 (2009)
      virus infection in adults.
AB  - To investigate the diagnostic accuracy of the QuickVue(r) Influenza A+B rapid
      test we conducted a prospective observational study in which this rapid test was
      compared with a real-time reverse transcription polymerase chain reaction (RT
      PCR) for pandemic influenza A H1N1 (2009) infection in Austrian adults. The
      sensitivity, specificity, and positive and negative predictive values of the
      QuickVue test compared with the RT-PCR were 26% (95% CI 18-35), 98% (95% CI 92
      100), 94% (95% CI 80-99) and 50% (95% CI 42-58), respectively. The prevalence of
      pandemic H1N1 (2009) virus infection among the 209 patients included in the study
      was 57%. Our data suggest that a positive QuickVue test provides considerable
      information for the diagnosis of pandemic influenza A H1N1 (2009) virus infection
      in young adults but that a negative QuickVue test result should, if relevant for
      patient management or public health measures, be verified using PCR.

PMID- 22145024
TI  - TRESK background K(+) channel is inhibited by PAR-1/MARK microtubule affinity
      regulating kinases in Xenopus oocytes.
AB  - TRESK (TWIK-related spinal cord K(+) channel, KCNK18) is a major background K(+)
      channel of sensory neurons. Dominant-negative mutation of TRESK is linked to
      familial migraine. This important two-pore domain K(+) channel is uniquely
      activated by calcineurin. The calcium/calmodulin-dependent protein phosphatase
      directly binds to the channel and activates TRESK current several-fold in Xenopus
      oocytes and HEK293 cells. We have recently shown that the kinase, which is
      responsible for the basal inhibition of the K(+) current, is sensitive to the
      adaptor protein 14-3-3. Therefore we have examined the effect of the 14-3-3
      inhibited PAR-1/MARK, microtubule-associated-protein/microtubule affinity
      regulating kinase on TRESK in the Xenopus oocyte expression system. MARK1, MARK2
      and MARK3 accelerated the return of TRESK current to the resting state after the
      calcium-dependent activation. Several other serine-threonine kinase types,
      generally involved in the modulation of other ion channels, failed to influence
      TRESK current recovery. MARK2 phosphorylated the primary determinant of
      regulation, the cluster of three adjacent serine residues (S274, 276 and 279) in
      the intracellular loop of mouse TRESK. In contrast, serine 264, the 14-3-3
      binding site of TRESK, was not phosphorylated by the kinase. Thus MARK2
      selectively inhibits TRESK activity via the S274/276/279 cluster, but does not
      affect the direct recruitment of 14-3-3 to the channel. TRESK is the first
      example of an ion channel phosphorylated by the dynamically membrane-localized
      MARK kinases, also known as general determinants of cellular polarity. These
      results raise the possibility that microtubule dynamics is coupled to the
      regulation of excitability in the neurons, which express TRESK background
      potassium channel.

PMID- 22145025
TI  - Down-regulation of DNA mismatch repair enhances initiation and growth of
      neuroblastoma and brain tumour multicellular spheroids.
AB  - Multicellular tumour spheroid (MCTS) cultures are excellent model systems for
      simulating the development and microenvironmental conditions of in vivo tumour
      growth. Many documented cell lines can generate differentiated MCTS when cultured
      in suspension or in a non-adhesive environment. While physiological and
      biochemical properties of MCTS have been extensively characterized, insight into
      the events and conditions responsible for initiation of these structures is
      lacking. MCTS are formed by only a small subpopulation of cells during surface
      associated growth but the processes responsible for this differentiation are
      poorly understood and have not been previously studied experimentally. Analysis
      of gene expression within spheroids has provided clues but to date it is not
      known if the observed differences are a cause or consequence of MCTS growth. One
      mechanism linked to tumourigenesis in a number of cancers is genetic instability
      arising from impaired DNA mismatch repair (MMR). This study aimed to determine
      the role of MMR in MCTS initiation and development. Using surface-associated N2a
      and CHLA-02-ATRT culture systems we have investigated the impact of impaired MMR
      on MCTS growth. Analysis of the DNA MMR genes MLH1 and PMS2 revealed both to be
      significantly down-regulated at the mRNA level compared with non-spheroid-forming
      cells. By using small interfering RNA (siRNA) against these genes we show that
      silencing of MLH1 and PMS2 enhances both MCTS initiation and subsequent
      expansion. This effect was prolonged over several passages following siRNA
      transfection. Down-regulation of DNA MMR can contribute to tumour initiation and
      progression in N2a and CHLA-02-ATRT MCTS models. Studies of surface-associated
      MCTS differentiation may have broader applications in studying events in the
      initiation of cancer foci.

PMID- 22145026
TI  - Activation of PPARgamma in myeloid cells promotes lung cancer progression and
      metastasis.
AB  - Activation of peroxisome proliferator-activated receptor-gamma (PPARgamma)
      inhibits growth of cancer cells including non-small cell lung cancer (NSCLC).
      Clinically, use of thiazolidinediones, which are pharmacological activators of
      PPARgamma is associated with a lower risk of developing lung cancer. However, the
      role of this pathway in lung cancer metastasis has not been examined well. The
      systemic effect of pioglitazone was examined in two models of lung cancer
      metastasis in immune-competent mice. In an orthotopic model, murine lung cancer
      cells implanted into the lungs of syngeneic mice metastasized to the liver and
      brain. As a second model, cancer cells injected subcutaneously metastasized to
      the lung. In both models systemic administration of pioglitazone increased the
      rate of metastasis. Examination of tissues from the orthotopic model demonstrated
      increased numbers of arginase I-positive macrophages in tumors from pioglitazone
      treated animals. In co-culture experiments of cancer cells with bone marrow
      derived macrophages, pioglitazone promoted arginase I expression in macrophages
      and this was dependent on the expression of PPARgamma in the macrophages. To
      assess the contribution of PPARgamma in macrophages to cancer progression,
      experiments were performed in bone marrow-transplanted animals receiving bone
      marrow from Lys-M-Cre+/PPARgamma(flox/flox) mice, in which PPARgamma is deleted
      specifically in myeloid cells (PPARgamma-Mac(neg)), or control
      PPARgamma(flox/flox) mice. In both models, mice receiving PPARgamma-Mac(neg) bone
      marrow had a marked decrease in secondary tumors which was not significantly
      altered by treatment with pioglitazone. This was associated with decreased
      numbers of arginase I-positive cells in the lung. These data support a model in
      which activation of PPARgamma may have opposing effects on tumor progression,
      with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on
      cells of the microenvironment, specifically myeloid cells.

PMID- 22145027
TI  - Conserved and divergent roles of Bcr1 and CFEM proteins in Candida parapsilosis
      and Candida albicans.
AB  - Candida parapsilosis is a pathogenic fungus that is major cause of hospital
      acquired infection, predominantly due to growth as biofilms on indwelling medical
      devices. It is related to Candida albicans, which remains the most common cause
      of candidiasis disease in humans. The transcription factor Bcr1 is an important
      regulator of biofilm formation in vitro in both C. parapsilosis and C. albicans.
      We show here that C. parapsilosis Bcr1 is required for in vivo biofilm
      development in a rat catheter model, like C. albicans. By comparing the
      transcription profiles of a bcr1 deletion in both species we found that
      regulation of expression of the CFEM family is conserved. In C. albicans, three
      of the five CFEM cell wall proteins (Rbt5, Pga7 and Csa1) are associated with
      both biofilm formation and acquisition of iron from heme, which is an important
      virulence characteristic. In C. parapsilosis, the CFEM family has undergone an
      expansion to 7 members. Expression of three genes (CFEM2, CFEM3, and CFEM6) is
      dependent on Bcr1, and is induced in low iron conditions. All three are involved
      in the acquisition of iron from heme. However, deletion of the three CFEM genes
      has no effect on biofilm formation in C. parapsilosis. Our data suggest that the
      role of the CFEM family in iron acquisition is conserved between C. albicans and
      C. parapsilosis, but their role in biofilm formation is not.

PMID- 22145028
TI  - Pre-clinical assessment of novel multivalent MSP3 malaria vaccine constructs.
AB  - BACKGROUND: MSP3 has been shown to induce protection against malaria in African
      children. The characterization of a family of Plasmodium falciparum merozoite
      surface protein 3 (MSP3) antigens sharing a similar structural organization,
      simultaneously expressed on the merozoite surface and targeted by a cross
      reactive network of protective antibodies, is intriguing and offers new
      perspectives for the development of subunit vaccines against malaria. METHODS:
      Eight recombinant polyproteins containing carefully selected regions of this
      family covalently linked in different combinations were all efficiently produced
      in Escherichia coli. The polyproteins consisted of one monovalent, one bivalent,
      one trivalent, two tetravalents, one hexavalent construct, and two tetravalents
      incorporating coiled-coil repeats regions from LSA3 and p27 vaccine candidates.
      RESULTS: All eight polyproteins induced a strong and homogeneous antibody
      response in mice of three distinct genotypes, with a dominance of cytophilic IgG
      subclasses, lasting up to six months after the last immunization. Vaccine-induced
      antibodies exerted a strong monocyte-mediated in vitro inhibition of P.
      falciparum growth. Naturally acquired antibodies from individuals living in an
      endemic area of Senegal recognized the polyproteins with a reactivity mainly
      constituted of cytophilic IgG subclasses. CONCLUSIONS: Combination of genetically
      conserved and antigenically related MSP3 proteins provides promising subunit
      vaccine constructs, with improved features as compared to the first generation
      construct employed in clinical trials (MSP3-LSP). These multivalent MSP3 vaccine
      constructs expand the epitope display of MSP3 family proteins, and lead to the
      efficient induction of a wider range of antibody subclasses, even in genetically
      different mice. These findings are promising for future immunization of
      genetically diverse human populations.

PMID- 22145029
TI  - NADPH oxidase-2 derived ROS dictates murine DC cytokine-mediated cell fate
      decisions during CD4 T helper-cell commitment.
AB  - NADPH oxidase-2 (Nox2)/gp91(phox) and p47(phox) deficient mice are prone to hyper
      inflammatory responses suggesting a paradoxical role for Nox2-derived reactive
      oxygen species (ROS) as anti-inflammatory mediators. The molecular basis for this
      mode of control remains unclear. Here we demonstrate that IFNgamma/LPS matured
      p47(phox-/-)-ROS deficient mouse dendritic cells (DC) secrete more IL-12p70 than
      similarly treated wild type DC, and in an in vitro co-culture model IFNgamma/LPS
      matured p47(phox-/-) DC bias more ovalbumin-specific CD4(+) T lymphocytes toward
      a Th1 phenotype than wild type (WT) DC through a ROS-dependent mechanism linking
      IL-12p70 expression to regulation of p38-MAPK activation. The Nox2-dependent ROS
      production in DC negatively regulates proinflammatory IL-12 expression in DC by
      constraining p38-MAPK activity. Increasing endogenous H(2)O(2) attenuates p38
      MAPK activity in IFNgamma/LPS stimulated WT and p47(phox-/-) DC, which suggests
      that endogenous Nox 2-derived ROS functions as a secondary messenger in the
      activated p38-MAPK signaling pathway during IL-12 expression. These findings
      indicate that ROS, generated endogenously by innate and adaptive immune cells,
      can function as important secondary messengers that can regulate cytokine
      production and immune cell cross-talk to control during the inflammatory
      response.

PMID- 22145030
TI  - Generation of glucose-responsive functional islets with a three-dimensional
      structure from mouse fetal pancreatic cells and iPS cells in vitro.
AB  - Islets of Langerhans are a pancreatic endocrine compartment consisting of insulin
      producing beta cells together with several other hormone-producing cells. While
      some insulin-producing cells or immature pancreatic cells have been generated in
      vitro from ES and iPS cells, islets with proper functions and a three-dimensional
      (3D) structure have never been successfully produced. To test whether islets can
      be formed in vitro, we first examined the potential of mouse fetal pancreatic
      cells. We found that E16.5 pancreatic cells, just before forming islets, were
      able to develop cell aggregates consisting of beta cells surrounded by glucagon
      producing alpha cells, a structure similar to murine adult islets. Moreover, the
      transplantation of these cells improved blood glucose levels in hyperglycemic
      mice. These results indicate that functional islets are formed in vitro from
      fetal pancreatic cells at a specific developmental stage. By adopting these
      culture conditions to the differentiation of mouse iPS cells, we developed a two
      step system to generate islets, i.e. immature pancreatic cells were first
      produced from iPS cells, and then transferred to culture conditions that allowed
      the formation of islets from fetal pancreatic cells. The islets exhibited
      distinct 3D structural features similar to adult pancreatic islets and secreted
      insulin in response to glucose concentrations. Transplantation of the islets
      improved blood glucose levels in hyperglycemic mice. In conclusion, the two-step
      culture system allows the generation of functional islets with a 3D structure
      from iPS cells.

PMID- 22145031
TI  - Independent colimitation for carbon dioxide and inorganic phosphorus.
AB  - Simultaneous limitation of plant growth by two or more nutrients is increasingly
      acknowledged as a common phenomenon in nature, but its cellular mechanisms are
      far from understood. We investigated the uptake kinetics of CO(2) and phosphorus
      of the algae Chlamydomonas acidophila in response to growth at limiting
      conditions of CO(2) and phosphorus. In addition, we fitted the data to four
      different Monod-type models: one assuming Liebigs Law of the minimum, one
      assuming that the affinity for the uptake of one nutrient is not influenced by
      the supply of the other (independent colimitation) and two where the uptake
      affinity for one nutrient depends on the supply of the other (dependent
      colimitation). In addition we asked whether the physiological response under
      colimitation differs from that under single nutrient limitation.We found no
      negative correlation between the affinities for uptake of the two nutrients,
      thereby rejecting a dependent colimitation. Kinetic data were supported by a
      better model fit assuming independent uptake of colimiting nutrients than when
      assuming Liebigs Law of the minimum or a dependent colimitation. Results show
      that cell nutrient homeostasis regulated nutrient acquisition which resulted in a
      trade-off in the maximum uptake rates of CO(2) and phosphorus, possibly driven by
      space limitation on the cell membrane for porters for the different nutrients.
      Hence, the response to colimitation deviated from that to a single nutrient
      limitation. In conclusion, responses to single nutrient limitation cannot be
      extrapolated to situations where multiple nutrients are limiting, which calls for
      colimitation experiments and models to properly predict growth responses to a
      changing natural environment. These deviations from single nutrient limitation
      response under colimiting conditions and independent colimitation may also hold
      for other nutrients in algae and in higher plants.

PMID- 22145032
TI  - Basic taste stimuli elicit unique responses in facial skin blood flow.
AB  - Facial expression changes characteristically with the emotions induced by basic
      tastes in humans. We tested the hypothesis that the five basic tastes also elicit
      unique responses in facial skin blood flow. Facial skin blood flow was measured
      using laser speckle flowgraphy in 16 healthy subjects before and during the
      application of basic taste stimuli in the oral cavity for 20 s. The skin blood
      flow in the eyelid increased in response to sweet and umami taste stimuli, while
      that in the nose decreased in response to a bitter stimulus. There was a
      significant correlation between the subjective hedonic scores accompanying these
      taste stimuli and the above changes in skin blood flow. These results demonstrate
      that sweet, umami, and bitter tastes induce unique changes in facial skin blood
      flow that reflect subjective hedonic scores.

PMID- 22145033
TI  - Seeking clarity within cloudy effluents: differentiating fungal from bacterial
      peritonitis in peritoneal dialysis patients.
AB  - BACKGROUND: Fungal peritonitis is a serious complication of peritoneal dialysis
      (PD) therapy with the majority of patients ceasing PD permanently. The aims of
      this study were to identify risk factors and clinical associations that may
      discriminate between fungal from bacterial peritonitis. METHODS: We
      retrospectively identified episodes of fungal peritonitis from 2001-2010 in PD
      patients at Liverpool and Westmead Hospitals (Australia). Fungal peritonitis
      cases were matched in a 1:2 ratio with patients with bacterial peritonitis from
      each institution's dialysis registry, occurring closest in time to the fungal
      episode. Patient demographic, clinical and outcome data were obtained from the
      medical records. RESULTS: Thirty-nine episodes of fungal peritonitis (rate of
      0.02 episodes per patient-year of dialysis) were matched with 78 episodes of
      bacterial peritonitis. Candida species were the commonest pathogens (35/39; 90%
      episodes) with Candida albicans (37%), Candida parapsilosis (32%) and Candida
      glabrata (13%) the most frequently isolated species. Compared to bacterial
      peritonitis, fungal peritonitis patients had received PD for significantly longer
      (1133 vs. 775 catheter-days; p = 0.016), were more likely to have had previous
      episodes of bacterial peritonitis (51% vs. 10%; p = 0.01), and to have received
      prior antibacterial therapy (51% vs. 10%; p = 0.01). Patients with fungal
      peritonitis were less likely to have fever and abdominal pain on presentation,
      but had higher rates of PD catheter removal (79% vs. 22%; p<0.005), and permanent
      transfer to haemodialysis (87% vs. 24%; p<0.005). Hospital length of stay was
      significantly longer in patients with fungal peritonitis (26.1 days vs. 12.6
      days; p = 0.017), but the all-cause 30-day mortality rate was similar in both
      groups. Fluconazole was a suitable empiric antifungal agent; with no Candida
      resistance detected. CONCLUSION: Prompt recognition of clinical risk factors,
      initiation of antifungal therapy and removal of PD catheters are key
      considerations in optimising outcomes.

PMID- 22145034
TI  - SLO-2 is cytoprotective and contributes to mitochondrial potassium transport.
AB  - Mitochondrial potassium channels are important mediators of cell protection
      against stress. The mitochondrial large-conductance "big" K(+) channel (mBK)
      mediates the evolutionarily-conserved process of anesthetic preconditioning
      (APC), wherein exposure to volatile anesthetics initiates protection against
      ischemic injury. Despite the role of the mBK in cardioprotection, the molecular
      identity of the channel remains unknown. We investigated the attributes of the
      mBK using C. elegans and mouse genetic models coupled with measurements of
      mitochondrial K(+) transport and APC. The canonical Ca(2+)-activated BK (or "maxi
      K") channel SLO1 was dispensable for both mitochondrial K(+) transport and APC in
      both organisms. Instead, we found that the related but physiologically-distinct
      K(+) channel SLO2 was required, and that SLO2-dependent mitochondrial K(+)
      transport was triggered directly by volatile anesthetics. In addition, a SLO2
      channel activator mimicked the protective effects of volatile anesthetics. These
      findings suggest that SLO2 contributes to protection from hypoxic injury by
      increasing the permeability of the mitochondrial inner membrane to K(+).

PMID- 22145035
TI  - LKB1 is an essential regulator of spermatozoa release during spermiation in the
      mammalian testis.
AB  - LKB1 acts as a master upstream protein kinase regulating a number of kinases
      involved in diverse cellular functions. Recent studies have suggested a role for
      LKB1 in male fertility. Male mice with reduced total LKB1 expression, including
      the complete absence of the major splice variant in testis (LKB1(S)), are
      completely infertile. We sought to further characterise these mice and determine
      the mechanism underlying this infertility. This involved expression studies of
      LKB1 in developing germ cells, morphological analysis of mature spermatozoa and
      histological studies of both the testis and epididymis using light microscopy and
      transmission electron microscopy. We conclude that a defect in the release of
      mature spermatids from the seminiferous epithelium (spermiation) during
      spermatozoan development is a major cause of the infertility phenotype. We also
      present evidence that this is due, at least in part, to defects in the breakdown
      of the junctions, known as ectoplasmic specialisations, between the sertoli cells
      of the testis epithelium and the heads of the maturing spermatids. Overall this
      study uncovers a critical role for LKB1 in spermiation, a highly regulated, but
      poorly understood process vital for male fertility.

PMID- 22145036
TI  - Post-transcriptional silencing of flavonol synthase mRNA in tobacco leads to
      fruits with arrested seed set.
AB  - Flavonoids are synthesized by phenylpropanoid pathway. They are known to
      participate in large number of physiological and biochemical processes in plants.
      Parthenocarpy and male sterility has earlier been reported by silencing chalcone
      synthase (CHS) encoding gene. Silencing of CHS has blocked the synthesis of most
      of useful flavonoids including flavan-3-ols and flavonols. Also, these studies
      could not identify whether parthenocarpy/male sterility were due to lack of
      flavan-3-ols or flavonols or both. Flavonol synthase (FLS) is an important enzyme
      of flavonoid pathway that catalyzes the formation of flavonols. In this article,
      we propose a novel strategy towards the generation of seedless or less-seeded
      fruits by downregulation of flavonol biosynthesis in tobacco (Nicotiana tabacum
      cv Xanthi) through post-transcriptional gene silencing (PTGS) of FLS encoding
      mRNA. The FLS silenced lines were observed for 20-80% reduction in FLS encoding
      gene expression and 25-93% reduction in flavonol (quercetin) content.
      Interestingly, these FLS silenced tobacco lines also showed reduction in their
      anthocyanidins content. While the content of flavan-3-ols (catechin, epi-catechin
      and epi-gallocatechin) was found to be increased in FLS silenced lines. The
      delayed flowering in FLS silenced lines could be due to decrease in level of
      indole acetic acid (IAA) at apical region of their shoots. Furthermore, the
      pollen germination was hampered and pollens were unable to produce functional
      pollen tube in FLS silenced tobacco lines. Pods of FLS silenced lines contained
      significantly less number of seeds. The in vitro and in vivo studies where 1 uM
      quercetin was supplied to germination media, documented the restoration of normal
      pollen germination and pollen tube growth. This finding identified the role of
      flavonols particularly quercetin in pollen germination as well as in the
      regulation of plant fertility. Results also suggest a novel approach towards
      generation of seedless/less-seeded fruits via PTGS of FLS encoding gene in
      plants.

PMID- 22145037
TI  - The effect of structural complexity, prey density, and "predator-free space" on
      prey survivorship at created oyster reef mesocosms.
AB  - Interactions between predators and their prey are influenced by the habitat they
      occupy. Using created oyster (Crassostrea virginica) reef mesocosms, we conducted
      a series of laboratory experiments that created structure and manipulated
      complexity as well as prey density and "predator-free space" to examine the
      relationship between structural complexity and prey survivorship. Specifically,
      volume and spatial arrangement of oysters as well as prey density were
      manipulated, and the survivorship of prey (grass shrimp, Palaemonetes pugio) in
      the presence of a predator (wild red drum, Sciaenops ocellatus) was quantified.
      We found that the presence of structure increased prey survivorship, and that
      increasing complexity of this structure further increased survivorship, but only
      to a point. This agrees with the theory that structural complexity may influence
      predator-prey dynamics, but that a threshold exists with diminishing returns.
      These results held true even when prey density was scaled to structural
      complexity, or the amount of "predator-free space" was manipulated within our
      created reef mesocosms. The presence of structure and its complexity (oyster
      shell volume) were more important in facilitating prey survivorship than
      perceived refugia or density-dependent prey effects. A more accurate indicator of
      refugia might require "predator-free space" measures that also account for the
      available area within the structure itself (i.e., volume) and not just on the
      surface of a structure. Creating experiments that better mimic natural conditions
      and test a wider range of "predator-free space" are suggested to better
      understand the role of structural complexity in oyster reefs and other complex
      habitats.

PMID- 22145038
TI  - Aged PROP1 deficient dwarf mice maintain ACTH production.
AB  - Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD)
      that typically advance from growth insufficiency diagnosed in infancy to include
      more severe growth hormone (GH) deficiency and progressive reduction in other
      anterior pituitary hormones, eventually including adrenocorticotropic hormone
      (ACTH) deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin,
      and thyroid stimulating hormone have been reported in the Prop1(null) (Prop1(-/
      )) and the Ames dwarf (Prop1(df/df)) mouse models, but corticotroph and pituitary
      adrenal axis function have not been thoroughly investigated. Here we report that
      the C57BL6 background sensitizes mutants to a wasting phenotype that causes
      approximately one third to die precipitously between weaning and adulthood, while
      remaining homozygotes live with no signs of illness. The wasting phenotype is
      associated with severe hypoglycemia. Circulating ACTH and corticosterone levels
      are elevated in juvenile and aged Prop1 mutants, indicating activation of the
      pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are
      capable of responding to restraint stress with further elevation of ACTH and
      corticosterone. Low blood glucose, an expected side effect of GH deficiency, is
      likely responsible for the elevated corticosterone level. These studies suggest
      that the mouse model differs from the human patients who display progressive
      hormone loss and hypocortisolism.

PMID- 22145039
TI  - Investigation of the climatic and environmental context of Hendra virus spillover
      events 1994-2010.
AB  - Hendra virus is a recently emerged bat-borne zoonotic agent with high lethality
      in horses and humans in Australia. This is a rare disease and the determinants of
      bat to horse transmission, including the factors that bring these hosts together
      at critical times, are poorly understood. In this cross-disciplinary study
      climatic and vegetation primary productivity variables are compared for the
      dispersed and heterogenic 1994-2010 outbreak sites. The significant occurrence of
      spillover events within the dry season (p =  0.013, 95% CI (0.57-0.98)) suggests
      seasonal forcing of transmission across species, or seasonal forcing of virus
      excretion by the reservoir host. We explore the evidence for both. Preliminary
      investigations of the spatial determinants of Hendra disease locations are also
      presented. We find that postal areas in the Australian state of Queensland in
      which pteropid fruit bat (flying fox) roosts occur are approximately forty times
      more likely (OR = 40.5, (95% CI (5.16, 317.52)) to be the location of Hendra
      spillover events. This appears to be independent of density of horses at these
      locations. We consider issues of scale of host resource use, land use change and
      limitations of existing data that challenge analysis and limit further conclusive
      outcomes. This investigation of a broad range of potential climatic and
      environmental influences provides a good base for future investigations. Further
      understanding of cross-species Hendra virus transmission requires better
      understanding of flying fox resource use in the urban-rural landscape.

PMID- 22145040
TI  - The Staphylococcus aureus peptidoglycan protects mice against the pathogen and
      eradicates experimentally induced infection.
AB  - Staphylococcus aureus, in spite of antibiotics, is still a major human pathogen
      causing a wide range of infections. The present study describes the new vaccine
      A170PG, a peptidoglycan-based vaccine. In a mouse model of infection, A170PG
      protects mice against a lethal dose of S. aureus. Protection lasts at least 40
      weeks and correlates with increased survival and reduced colonization. Protection
      extends into drug-resistant (MRSA or VISA) and genetically diverse clinical
      strains. The vaccine is effective when administered - in a single dose and
      without adjuvant - by the intramuscular, intravenous or the aerosol routes and
      induces active as well as passive immunization. Of note, A170PG also displays
      therapeutic activity, eradicating staphylococci, even when infection is systemic.
      Sustained antibacterial activity and induction of a strong and rapid anti
      inflammatory response are the mechanisms conferring therapeutic efficacy to
      A170PG.

PMID- 22145041
TI  - Mental fatigue modulates dynamic adaptation to perceptual demand in speeded
      detection.
AB  - When stimulus intensity in simple reaction-time tasks randomly varies across
      trials, detection speed usually improves after a low-intensity trial. With
      auditory stimuli, this improvement was often found to be asymmetric, being
      greater on current low-intensity trials. Our study investigated (1) whether
      asymmetric sequential intensity adaptation also occurs with visual stimuli; (2)
      whether these adjustments reflect decision-criterion shifts or, rather, a
      modulation of perceptual sensitivity; and (3) how sequential intensity adaptation
      and its underlying mechanisms are affected by mental fatigue induced through
      prolonged performance. In a continuous speeded detection task with randomly
      alternating high- and low-intensity visual stimuli, the reaction-time benefit
      after low-intensity trials was greater on subsequent low- than high-intensity
      trials. This asymmetry, however, only developed with time on task (TOT). Signal
      detection analyses showed that the decision criterion transiently became more
      liberal after a low-intensity trial, whereas observer sensitivity increased when
      the preceding and current stimulus were of equal intensity. TOT-induced mental
      fatigue only affected sensitivity, which dropped more on low- than on high
      intensity trials. This differential fatigue-related sensitivity decrease
      selectively enhanced the impact of criterion down-shifts on low-intensity trials,
      revealing how the interplay of two perceptual mechanisms and their modulation by
      fatigue combine to produce the observed overall pattern of asymmetric performance
      adjustments to varying visual intensity in continuous speeded detection. Our
      results have implications for similar patterns of sequential demand adaptation in
      other cognitive domains as well as for real-world prolonged detection
      performance.

PMID- 22145042
TI  - Transient mTOR inhibition facilitates continuous growth of liver tumors by
      modulating the maintenance of CD133+ cell populations.
AB  - The mammalian target of the rapamycin (mTOR) pathway, which drives cell
      proliferation, is frequently hyperactivated in a variety of malignancies.
      Therefore, the inhibition of the mTOR pathway has been considered as an
      appropriate approach for cancer therapy. In this study, we examined the roles of
      mTOR in the maintenance and differentiation of cancer stem-like cells (CSCs), the
      conversion of conventional cancer cells to CSCs and continuous tumor growth in
      vivo. In H-Ras-transformed mouse liver tumor cells, we found that pharmacological
      inhibition of mTOR with rapamycin greatly increased not only the CD133+
      populations both in vitro and in vivo but also the expression of stem cell-like
      genes. Enhancing mTOR activity by over-expressing Rheb significantly decreased
      CD133 expression, whereas knockdown of the mTOR yielded an opposite effect. In
      addition, mTOR inhibition severely blocked the differentiation of CD133+ to CD133
      liver tumor cells. Strikingly, single-cell culture experiments revealed that
      CD133- liver tumor cells were capable of converting to CD133+ cells and the
      inhibition of mTOR signaling substantially promoted this conversion. In serial
      implantation of tumor xenografts in nude BALB/c mice, the residual tumor cells
      that were exposed to rapamycin in vivo displayed higher CD133 expression and had
      increased secondary tumorigenicity compared with the control group. Moreover,
      rapamycin treatment also enhanced the level of stem cell-associated genes and
      CD133 expression in certain human liver tumor cell lines, such as Huh7, PLC/PRC/7
      and Hep3B. The mTOR pathway is significantly involved in the generation and the
      differentiation of tumorigenic liver CSCs. These results may be valuable for the
      design of more rational strategies to control clinical malignant HCC using mTOR
      inhibitors.

PMID- 22145043
TI  - Scavenger receptor mediates systemic RNA interference in ticks.
AB  - RNA interference is an efficient method to silence gene and protein expressions.
      Here, the class B scavenger receptor CD36 (SRB) mediated the uptake of exogenous
      dsRNAs in the induction of the RNAi responses in ticks. Unfed female
      Haemaphysalis longicornis ticks were injected with a single or a combination of
      H. longicornis SRB (HlSRB) dsRNA, vitellogenin-1 (HlVg-1) dsRNA, and vitellogenin
      receptor (HlVgR) dsRNA. We found that specific and systemic silencing of the
      HlSRB, HlVg-1, and HlVgR genes was achieved in ticks injected with a single dsRNA
      of HlSRB, HlVg-1, and HlVgR. In ticks injected first with HlVg-1 or HlVgR dsRNA
      followed 96 hours later with HlSRB dsRNA (HlVg-1/HlSRB or HlVgR/HlSRB), gene
      silencing of HlSRB was achieved in addition to first knockdown in HlVg-1 or
      HlVgR, and prominent phenotypic changes were observed in engorgement, mortality,
      and hatchability, indicating that a systemic and specific double knockdown of
      target genes had been simultaneously attained in these ticks. However, in ticks
      injected with HlSRB dsRNA followed 96 hours later with HlVg-1 or HlVgR dsRNAs,
      silencing of HlSRB was achieved, but no subsequent knockdown in HlVgR or HlVg-1
      was observed. The Westernblot and immunohistochemical examinations revealed that
      the endogenous HlSRB protein was fully abolished in midguts of ticks injected
      with HlSRB/HlVg-1 dsRNAs but HlVg-1 was normally expressed in midguts, suggesting
      that HlVg-1 dsRNA-mediated RNAi was fully inhibited by the first knockdown of
      HlSRB. Similarly, the abolished localization of HlSRB protein was recognized in
      ovaries of ticks injected with HlSRB/HlVgR, while normal localization of HlVgR
      was observed in ovaries, suggesting that the failure to knock-down HlVgR could be
      attributed to the first knockdown of HlSRB. In summary, we demonstrated for the
      first time that SRB may not only mediate the effective knock-down of gene
      expression by RNAi but also play essential roles for systemic RNAi of ticks.

PMID- 22145044
TI  - Runx1 loss minimally impacts long-term hematopoietic stem cells.
AB  - RUNX1 encodes a DNA binding subunit of the core-binding transcription factors and
      is frequently mutated in acute leukemia, therapy-related leukemia,
      myelodysplastic syndrome, and chronic myelomonocytic leukemia. Mutations in RUNX1
      are thought to confer upon hematopoietic stem cells (HSCs) a pre-leukemic state,
      but the fundamental properties of Runx1 deficient pre-leukemic HSCs are not well
      defined. Here we show that Runx1 deficiency decreases both apoptosis and
      proliferation, but only minimally impacts the frequency of long term repopulating
      HSCs (LT-HSCs). It has been variously reported that Runx1 loss increases LT-HSC
      numbers, decreases LT-HSC numbers, or causes age-related HSC exhaustion. We
      attempt to resolve these discrepancies by showing that Runx1 deficiency alters
      the expression of several key HSC markers, and that the number of functional LT
      HSCs varies depending on the criteria used to score them. Finally, we identify
      genes and pathways, including the cell cycle and p53 pathways that are
      dysregulated in Runx1 deficient HSCs.

PMID- 22145045
TI  - Widespread regulation of miRNA biogenesis at the Dicer step by the cold-inducible
      RNA-binding protein, RBM3.
AB  - MicroRNAs (miRNAs) play critical roles in diverse cellular events through their
      effects on translation. Emerging data suggest that modulation of miRNA biogenesis
      at post-transcriptional steps by RNA-binding proteins is a key point of
      regulatory control over the expression of some miRNAs and the cellular processes
      they influence. However, the extent and conditions under which the miRNA pathway
      is amenable to regulation at posttranscriptional steps are poorly understood.
      Here we show that RBM3, a cold-inducible, developmentally regulated RNA-binding
      protein and putative protooncogene, is an essential regulator of miRNA
      biogenesis. Utilizing miRNA array, Northern blot, and PCR methods, we observed
      that over 60% of miRNAs detectable in a neuronal cell line were significantly
      downregulated by knockdown of RBM3. Conversely, for select miRNAs assayed by
      Northern blot, induction of RBM3 by overexpression or mild hypothermia increased
      their levels. Changes in miRNA expression were accompanied by changes in the
      levels of their ~70 nt precursors, whereas primary transcript levels were
      unaffected. Mechanistic studies revealed that knockdown of RBM3 does not reduce
      Dicer activity or impede transport of pre-miRNAs into the cytoplasm. Rather, we
      find that RBM3 binds directly to ~70 nt pre-miRNA intermediates and promotes / de
      represses their ability as larger ribonucleoproteins (pre-miRNPs) to associate
      with active Dicer complexes. Our findings suggest that the processing of a
      majority of pre-miRNPs by Dicer is subject to an intrinsic inhibitory influence
      that is overcome by RBM3 expression. RBM3 may thus orchestrate changes in miRNA
      expression during hypothermia and other cellular stresses, and in the euthermic
      contexts of early development, differentiation, and oncogenesis where RBM3
      expression is highly elevated. Additionally, our data suggest that temperature
      dependent changes in miRNA expression mediated by RBM3 may contribute to the
      therapeutic effects of hypothermia, and are an important variable to consider in
      in vitro studies of translation-dependent cellular events.

PMID- 22145046
TI  - Direct sensing of endothelial oxidants by vascular endothelial growth factor
      receptor-2 and c-Src.
AB  - BACKGROUND: ADPH oxidase-derived reactive oxygen species (ROS) play important
      roles in redox homeostasis and signal transduction in endothelial cells (ECs). We
      previously demonstrated that c-Src plays a key role in VEGF-induced, ROS
      dependent selective activation of PI3K-Akt but not PLCgamma-1-ERK1/2 signaling
      pathways. The aim of the present study was to understand how VEGFR-2-c-Src
      signaling axis 'senses' NADPH oxidase-derived ROS levels and couples VEGF
      activation of c-Src to the redox state of ECs. METHODOLOGY/PRINCIPAL FINDINGS:
      Using biotinylated probe that detects oxidation of cysteine thiol (cys-OH) in
      intracellular proteins, we demonstrate that VEGF induced oxidative modification
      in c-Src and VEGFR-2, and that reduction in ROS levels using siRNA against
      p47(phox) subunit of Rac1-dependent NADPH oxidase inhibited this phenomenon. Co
      immunoprecipitation studies using human coronary artery ECs (HCAEC) showed that
      VEGF-induced ROS-dependent interaction between VEGFR-2 and c-Src correlated with
      their thiol oxidation status. Immunofluorescence studies using antibodies against
      internalized VEGFR-2 and c-Src demonstrated that VEGF-induced subcellular co
      localization of these tyrosine kinases were also dependent on NADPH oxidsase
      derived ROS. CONCLUSION/SIGNIFICANCE: These results demonstrate that VEGF induces
      cysteine oxidation in VEGFR-2 and c-Src in an NADPH oxidase-derived ROS-dependent
      manner, suggesting that VEGFR-2 and c-Src can 'sense' redox levels in ECs. The
      data also suggest that thiol oxidation status of VEGFR-2 and c-Src correlates
      with their ability to physically interact with each other and c-Src activation.
      Taken together, these findings suggest that prior to activating downstream c-Src
      PI3K-Akt signaling pathway, VEGFR-2-c-Src axis requires an NADPH oxidase-derived
      ROS threshold in ECs.

PMID- 22145047
TI  - Accessible surfaces of beta proteins increase with increasing protein molecular
      mass more rapidly than those of other proteins.
AB  - Here we present a systematic analysis of accessible surface areas and hydrogen
      bonds of 2554 globular proteins from four structural classes (all-alpha, all
      beta, alpha/beta and alpha+beta proteins) that is aimed to learn in which
      structural class the accessible surface area increases with increasing protein
      molecular mass more rapidly than in other classes, and what structural
      peculiarities are responsible for this effect. The beta structural class of
      proteins was found to be the leader, with the following possible explanations of
      this fact. First, in beta structural proteins, the fraction of residues not
      included in the regular secondary structure is the largest, and second, the
      accessible surface area of packaged elements of the beta-structure increases more
      rapidly with increasing molecular mass in comparison with the alpha-structure.
      Moreover, in the beta structure, the probability of formation of backbone
      hydrogen bonds is higher than that in the alpha helix for all residues of
      alpha+beta proteins (the average probability is 0.73+/-0.01 for the beta
      structure and 0.60+/-0.01 for the alpha-structure without proline) and alpha/beta
      proteins, except for asparagine, aspartic acid, glycine, threonine, and serine
      (0.70+/-0.01 for the beta-structure and 0.60+/-0.01 for the alpha-structure
      without the proline residue). There is a linear relationship between the number
      of hydrogen bonds and the number of amino acid residues in the protein (Number of
      hydrogen bonds=0.678.number of residues-3.350).

PMID- 22145048
TI  - The metabolic reprogramming evoked by nitrosative stress triggers the anaerobic
      utilization of citrate in Pseudomonas fluorescens.
AB  - Nitrosative stress is an ongoing challenge that most organisms have to contend
      with. When nitric oxide (NO) that may be generated either exogenously or
      endogenously encounters reactive oxygen species (ROS), it produces a set of toxic
      moieties referred to as reactive nitrogen species (RNS). As these RNS can
      severely damage essential biomolecules, numerous organisms have evolved elaborate
      detoxification strategies to nullify RNS. However, the contribution of cellular
      metabolism in fending off nitrosative stress is poorly understood. Using a
      variety of functional proteomic and metabolomic analyses, we have identified how
      the soil microbe Pseudomonas fluorescens reprogrammed its metabolic networks to
      survive in an environment enriched by sodium nitroprusside (SNP), a generator of
      nitrosative stress. To combat the RNS-induced ineffective aconitase (ACN) and
      tricarboxylic acid (TCA) cycle, the microbe invoked the participation of citrate
      lyase (CL), phosphoenolpyruvate carboxylase (PEPC) and pyruvate phosphate
      dikinase (PPDK) to convert citrate, the sole source of carbon into pyruvate and
      ATP. These enzymes were not evident in the control conditions. This metabolic
      shift was coupled to the concomitant increase in the activities of such classical
      RNS detoxifiers as nitrate reductase (NR), nitrite reductase (NIR) and S
      nitrosoglutathione reductase (GSNOR). Hence, metabolism may hold the clues to the
      survival of organisms subjected to nitrosative stress and may provide therapeutic
      cues against RNS-resistant microbes.

PMID- 22145049
TI  - Aquaporin-5: a marker protein for proliferation and migration of human breast
      cancer cells.
AB  - Aquaporin (AQP) is a family of transmembrane proteins for water transport. Recent
      studies revealed that AQPs are likely to play a role in tumor progression and
      invasion. We aimed to examine the potential role of AQP5 in the progression of
      human breast cancer cells. Expression of AQP5 mRNA and protein was seen in human
      breast cancer cell line (both MCF7 and MDA-MB-231) by RT-PCR and immunoblotting
      analysis. Immunoperoxidase labeling of AQP5 was observed at ductal epithelial
      cells of human breast tissues. In benign tumor, AQP5 labeling was mainly seen at
      the apical domains of ductal epithelial cells. In contrast, in invasive ductal
      carcinoma, prominent AQP5 labeling was associated with cancer cells, whereas some
      ducts were unlabeled and apical polarity of AQP5 in ducts was lost. Cell
      proliferation (BrdU incorporation assay) and migration of MCF7 cells were
      significantly attenuated by lentivirus-mediated AQP5-shRNA transduction.
      Hyperosmotic stress induced by sorbitol treatment (100 mM, 24 h) reduced AQP5
      expression in MCF7 cells, which was also associated with a significant reduction
      in cell proliferation and migration. Taken together, prominent AQP5 expression in
      breast cancer cells with the loss of polarity of ductal epithelial cells was seen
      during the progression of breast carcinoma. shRNA- or hyperosmotic stress-induced
      reduction in AQP5 expression of MCF7 cells was associated with significantly
      reduced cell proliferation and migration. In conclusion, AQP5 overexpression is
      likely to play a role in cell growth and metastasis of human breast cancer and
      could be a novel target for anti-breast cancer treatment.

PMID- 22145050
TI  - Selective ion changes during spontaneous mitochondrial transients in intact
      astrocytes.
AB  - The bioenergetic status of cells is tightly regulated by the activity of
      cytosolic enzymes and mitochondrial ATP production. To adapt their metabolism to
      cellular energy needs, mitochondria have been shown to exhibit changes in their
      ionic composition as the result of changes in cytosolic ion concentrations.
      Individual mitochondria also exhibit spontaneous changes in their electrical
      potential without altering those of neighboring mitochondria. We recently
      reported that individual mitochondria of intact astrocytes exhibit spontaneous
      transient increases in their Na(+) concentration. Here, we investigated whether
      the concentration of other ionic species were involved during mitochondrial
      transients. By combining fluorescence imaging methods, we performed a
      multiparameter study of spontaneous mitochondrial transients in intact resting
      astrocytes. We show that mitochondria exhibit coincident changes in their Na(+)
      concentration, electrical potential, matrix pH and mitochondrial reactive oxygen
      species production during a mitochondrial transient without involving detectable
      changes in their Ca(2+) concentration. Using widefield and total internal
      reflection fluorescence imaging, we found evidence for localized transient
      decreases in the free Mg(2+) concentration accompanying mitochondrial Na(+)
      spikes that could indicate an associated local and transient enrichment in the
      ATP concentration. Therefore, we propose a sequential model for mitochondrial
      transients involving a localized ATP microdomain that triggers a Na(+)-mediated
      mitochondrial depolarization, transiently enhancing the activity of the
      mitochondrial respiratory chain. Our work provides a model describing ionic
      changes that could support a bidirectional cytosol-to-mitochondria ionic
      communication.

PMID- 22145051
TI  - [Dystocic expulsion of thoracopagus conjoined twins in the Talangai hospital,
      Republic of Congo].

PMID- 22145052
TI  - Elimination of leprosy as a public health problem by 2000 AD: an epidemiological
      perspective.
AB  - INTRODUCTION: Leprosy is caused by Mycobacterium leprae and manifests as damage
      to the skin and peripheral nerves. The disease is dreaded because it causes
      deformities, blindness and disfigurement. Worldwide, 2 million people are
      estimated to be disabled by leprosy. Multidrug therapy is highly effective in
      curing leprosy, but treating the nerve damage is much more difficult. The World
      Health Assembly targeted to eliminate leprosy as a public health problem from the
      world by 2000. The objective of the review was to assess the successes of the
      leprosy elimination strategy, elimination hurdles and the way forward for leprosy
      eradication. METHODS: A structured search was used to identify publications on
      the elimination strategy. The keywords used were leprosy, elimination and 2000.
      To identify potential publications, we included papers on leprosy elimination
      monitoring, special action projects for the elimination of leprosy, modified
      leprosy elimination campaigns, and the Global Alliance to eliminate leprosy from
      the following principal data bases: Cochrane data base of systematic reviews,
      PubMed, Medline, EMBASE, and the Leprosy data base. We also scanned reference
      lists for important citations. Key leprosy journals including WHO publications
      were also reviewed. RESULTS: The search identified 63 journal publications on
      leprosy-related terms that included a form of elimination of which 19
      comprehensively tackled the keywords including a book on leprosy elimination. In
      1991, the 44th World Health Assembly called for the elimination of leprosy as a
      public health problem in the world by 2000. Elimination was defined as less than
      one case of leprosy per 10000-population. Elimination has been made possible by a
      confluence of several orders of opportunities: the scientific (the natural
      history of leprosy at the present state of knowledge), technological (multi-drug
      therapy and the blister pack); political (commitment of governments) and
      financial (support from NGOs for example the Nippon Foundation that supplies free
      multi-drug therapy) opportunities. Elimination created the unrealistic
      expectation that the leprosy problem could be solved by 2000. First, the
      elimination goal was not feasible in several areas which had high incidence of
      leprosy. Even if elimination was to be attained, significant numbers of new cases
      of leprosy would continue to occur and many people with physical imperfections,
      severe psychological, economic and social problems caused by leprosy would need
      continuous assistance. Extra-human reservoirs of Mycobacterium leprae, the
      relationship between leprosy and poverty, prevention of disabilities, lack of a
      reliable laboratory test to detect subclinical infection and a vaccine are also
      challenging issues. CONCLUSION: The evidence base available to inform on leprosy
      elimination is highly positive with the availability of multi-drug therapy
      blister packs. There are concerns that leprosy was not the right disease to be
      targeted for elimination as there are no reliable diagnostic tests to detect
      subclinical infection including the lack of a vaccine, extra-human reservoirs
      (monkeys and armadillos), increase in the burden of child cases, no good
      epidemiological indicator as prevalence instead of incidence is used to measure
      elimination. Multi-drug therapy treats leprosy very well but there is no proof
      that it concurrently interrupts transmission. The high social stigma, prevention
      of disabilities, and the relationship between leprosy and poverty are still major
      concerns.

PMID- 22145053
TI  - Pattern of irritable bowel syndrome and its impact on quality of life in primary
      health care center attendees, Suez governorate, Egypt.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS) is one of the most common disorders
      diagnosed by gastroenterologists and a common cause of general practice visits.
      Although this disease is not life threatening, patients with IBS seem to be
      seriously affected in their everyday life. The study was designed to explore the
      pattern of IBS in clinical practice and the impact on the quality of life.
      METHODS: This is a case control descriptive study. 117 individuals were included
      in this study. Rome II criteria were used for the diagnosis of IBS. Impact of IBS
      on patient's quality of life was determined by irritable bowel syndrome quality
      of life (IBS-QOL) questionnaire. RESULTS: Prevalence of IBS among the study
      sample was 34.2%. 10% were IBS-Diarrhea, 37.5% were IBS-Constipation and 52.5%
      were alternators. There is statistical insignificant relationship between IBS (+)
      and age while it was a significant relation regarding gender (more common among
      women 80%). There is statistical significance relationship between IBS (+) on one
      hand and marital status and occupational status on the other hand. Patients with
      IBS had statistically significant lower scores for all IBS- QOL domains compared
      with the control group. CONCLUSION: IBS is a prevalent disorder that affects
      females more than males and it has significant impacts on work, lifestyle and
      social well-being.

PMID- 22145054
TI  - Baseline CD4+ T lymphocyte cell counts, hepatitis B and C viruses seropositivity
      in adults with Human Immunodeficiency Virus infection at a tertiary hospital in
      Nigeria.
AB  - BACKGROUND: Ekiti State of Nigeria is known to have the lowest prevalence of HIV
      in Nigeria. University Teaching Hospital (UTH), Ado Ekiti was recently upgraded
      to serve as one of the three centres for HIV/AIDS referral, diagnosis and
      treatment in Ekiti State. We evaluated the baseline immunologic and biochemical
      parameters of patients presenting at the ART clinic of University Teaching
      Hospital, Ado Ekiti, Ekiti State. METHODS: All HIV seropositive patients not yet
      on antiretroviral therapy, who presented at the ART Clinic within the study
      period had at the first visit to the clinic, their blood sample taken for CD4
      cell counts estimation, HBsAg and anti- HCV screening, ALT, AST as well as
      hemoglobin estimation as part of the routine workup to assess their disease
      health status and need for antiretroviral therapy. Statistical significance was
      taken as p< 0.05. RESULTS: A total of 273 patients comprising 79 (28.9%) males
      and 194 (71.1%) females were included in the study (F:M = 2.46: 1). The mean age
      of the study population was 36.21 +/- 10.20 years with mean age of males (39.52
      +/- 9.95 years) significantly higher than females (34.88 +/- 10.02; p=0.001). The
      overall prevalence of HBsAg in the study population was 6.6% with a sex specific
      prevalence of 8.1% and 6% for males and females, respectively. No statistically
      significance difference in the mean serum alanine transaminase, serum aspartate
      transaminase, hemoglobin and CD4+ T- Lymphocytes cell count of those who had
      HBsAg negative status compared to those who had HBsAg positive status. Two (0.7%)
      of the patients had positive serum anti HCV antibodies. The CD4+ T- Lymphocytes
      cell count ranged between 5 - 1050 cells/ul with a mean of 286.19 +/- 233.31
      cells/ul. The majority of patients (71.8%) had a CD4+ T- Lymphocytes cell count <
      350 cells/ul. CONCLUSION: At the time of presentation, majority of our patients
      had a CD4+ T- Lymphocytes cell count less than 350 cells/ul consistent with
      significant immune-suppression. More sustained and vigorous awareness campaigns
      still need to be done in Ekiti State to diagnose this disease early. There is
      also a need to accelerate the integration of hepatitis B virus screening and
      treatment programme into HIV/AIDS programme because of the morbidity and
      mortality implication of HBV and HIV co-infection.

PMID- 22145055
TI  - Knowledge and practices relating to malaria in a semi-urban area of Cameroon:
      choices and sources of antimalarials, self-treatment and resistance.
AB  - INTRODUCTION: Malaria is a major public health problem in Sub-Saharan Africa
      where it kills a child under the age of five every 30 seconds. In Cameroon,
      malaria accounts for 40-45% of medical consultations, 57% of hospitalization days
      and 40% of mortality among children below 5 years. Community knowledge and
      practices can enhance the fight against this disease. The aim of the study was to
      make a local analysis of the people's knowledge and practices relating to the
      choice and source of antimalarials, self-medication, malaria dosage and
      resistance in order to establish behavioural baseline and epidemiological
      determinants and their implications for malaria control. METHODS: The design was
      a community-based cross-sectional study in a semi-urban setting. The survey
      consisted of 253 volunteer participants (from among 350 contacted) from different
      socio-demographic backgrounds to whom structured questionnaires were
      administered. The respondent's consent was sought and gained and subjects who
      could not read or write or understand English language were communicated to in
      the local language. The questionnaire was administered by trained interviewers
      according to the schedule of the respondent. The data was analysed using SPSS.
      RESULTS: Antimalarials commonly cited for malaria treatment were chloroquine
      (26.1%) and nivaquine (14.6%) and analgesics: panadol (23%) and paracetamol
      (12.3%) including native drugs (6.3%). 141(55.7%) (95% confidence interval (CI):
      49.6-61.8%) participants practiced self-medication of malaria. 26.1% participants
      knew the correct adult malarial dosage for chloroquine or nivaquine. 125(40.4%)
      (95% CI: 34.4-46.7%) participants got their antimalarials from health centers,
      27(10.6%) from shops, 24(9.5%) from hawkers, 23(9.1%) from the open market and 16
      (6.3%) from herbalists. 66 (26.1%) (95% CI: 20.7-31.5%) participants knew the
      correct adult dosage for chloroquine or nivaquine treatment of malaria. 85(33.6%)
      (95% CI: 27.8-36.6%) participants had correct knowledge of malarial resistance.
      Of the 85 (33.6%) participants who had correct knowledge of antimalarial drug
      resistance, 52(20.6%) ascribed antimalarial drug resistance to continuous fever
      for a long time during treatment, 15 (5.9%) to serious fever during treatment and
      18 (7.1%) when chloroquine does not stop fever. 23(27.1%) participants with
      correct knowledge of malarial resistance were in the 31-35 age group bracket
      compared with other age groups (P=0.1). There was a significant difference in
      correct knowledge of malarial resistance and participant's profession (p=0.0).
      CONCLUSION: Malaria self-medication is common in Ndu but knowledge of
      antimalarial drug resistance is poor. Improvement in the self-treatment of
      malaria could be attained by providing clear information on choices of drugs for
      malaria treatment. Proper health information on the rational use of ant-malarial
      drugs must be provided in an appropriate manner to all groups of people in the
      society including village health workers, women associations, churches, school
      children, "Mngwah" opinion leaders, herbalists, health workers and chemists. Self
      medication should be improved upon by giving correct information on the dosage of
      malaria treatment on radio, television, posters and newspapers because banning it
      will push many people to use it in hiding.

PMID- 22145056
TI  - From DOTS to the Stop TB Strategy: DOTS coverage and trend of tuberculosis
      notification in Ebonyi, southeastern Nigeria, 1998-2009.
AB  - BACKGROUND: Nigeria ranks fourth among the 22 high tuberculosis (TB) burden
      countries. The estimated incidence of all TB cases in 2009 was 311/100,000
      population. Since the implementation of DOTS in Ebonyi state, southeast Nigeria,
      the epidemiology of TB in the region has not been documented. Therefore, the
      objective of this study was to assess the type and case notification dynamics of
      TB following DOTS expansion and to examine age- and sex-specific trends in TB
      notification rate. METHODS: A retrospective trend analysis of case notification
      data from the Ebonyi State Ministry of Health records from 1998 to 2009 was
      conducted. Patients were diagnosed according to the National TB and Leprosy
      Control Programme guidelines. Denominators for TB notifications were derived from
      population census data. RESULTS: Of the 24, 475 cases notified between 1998 and
      2009, 66% were smear-positive, 31% smear-negative and 3% had extra-pulmonary
      tuberculosis. Overall, the proportion of new smear-positive cases notified
      decreased continuously from 67% to 48% in 2009 while that of smear-negative cases
      increased from 29% to 40% in 2009. In 2005, 13 (100%) of the local government
      areas were covered by DOTS. Despite initial increase in case notification with
      DOTS expansion, the case notification rate had a mean annual decline of 3.1% for
      all TB cases (falling from 123/100,000 to 77/100,000), and of 5% for smear
      positive patients (falling from 80/100,000 to 32/100,000). Smear-positive
      notification rate in children <14 years was consistently low while 25-34-year-old
      persons were affected most. However, smear-positive rates among persons aged =65
      years did not change. Overall, annual new smear-positive notification rates were
      persistently lower in females than males. CONCLUSION: TB notification rate shows
      a decreasing trend in our region with a pool of infectious cases in young
      persons. Additional targeted, type and age-/sex- specific interventions for TB
      control are needed.

PMID- 22145057
TI  - Sources of drug information and their influence on the prescribing behaviour of
      doctors in a teaching hospital in Ibadan, Nigeria.
AB  - BACKGROUND: Pharmaceutical drug promotion is a means of informing health
      professionals about new drugs. The approach is often times unethical and
      inappropriate and may promote irrational prescribing. Dearth of information on
      impact of pharmaceutical drug promotion on prescribing behaviour of doctors in
      developing African countries has necessitated this study. We therefore aimed to
      determine the sources of drug information for doctors working in a teaching
      hospital in Nigeria and to assess the self-reported impact of the sources on
      their prescribing behaviour. METHODS: A total of 163 doctors working at the
      University College Hospital (UCH), Ibadan in Nigeria were evaluated with a
      questionnaire for their demographics and sources of drug information. For doctors
      who relied on drug promotion, they were asked to self-report and self-rate their
      opinion on extent of interactions with pharmaceutical companies as well as how
      such interactions had impacted on their prescribing behaviour. Apart from the
      demographics, each question was evaluated with a typical five-level Likert item.
      Data analyses were with simple descriptive statistics. RESULTS: Of the 400
      doctors working at UCH, only 40.8% participated in the study. Drug information
      was sourced from colleagues (161, 98.8%), reference books (158, 96.9%),
      pharmaceutical sales representatives-PSRs (152, 93.2%), promotion materials (151,
      92.6%), scientific papers/journals/internet (149, 91.4%), and drug promotion
      forum/product launches (144, 88.3%). Each source was highly utilized but there
      was no wide variation in their pattern of use. According to the self-report of
      over a half of the respondents, PSRs was an accurate and reliable drug
      information resource; PSRs increased their awareness of the promoted drugs; and
      their prescribing behaviours were influenced by information from PSRs.
      CONCLUSION: Respondents tend to rely on a broad range of drug information
      resources which include potentially inappropriate resources such as PSRs. Since
      this study was based on self-report, the influence of drug information resources
      reported by the respondents on their prescribing behaviour may have been
      underestimated. Measures should be taken to minimize interactions between PSRs
      and the respondents.

PMID- 22145058
TI  - Validation of the use of POSSUM score in enteric perforation peritonitis -
      results of a prospective study.
AB  - INTRODUCTION: The objective of the study was to present our last 5-years
      experience of peritonitis and validate POSSUM score in predicting mortality and
      morbidity in patients of enteric perforation (EP) peritonitis. METHODS: Data was
      collected prospectively for all peritonitis cases admitted in single surgical
      unit from January 2005 to December 2009. Parameters for calculating POSSUM were
      also retrieved; in these patients, O:E (Observed vs. Expected) ratio of mortality
      and morbidity were estimated after calculating predicted mortality and morbidity
      by exponential regression equations. RESULTS: 887 patients with peritonitis were
      admitted and treated in this unit during the 5 years of study period. Duodenal
      (n=431; 48%) followed by ileal (n=380; 42.8%) perforations were the commonest.
      Mean age of the patients was 34 years and 86% were males. Mean delay in
      presentation was 78.5 hrs. Mean duration of hospital and ICU stay was 13 and 7.2
      days. Postoperative complications were seen in 481 (54%) patients, and 90 (10%)
      patients died. POSSUM scores and predicted mortality/morbidity were calculated in
      380 patients of ileal perforation peritonitis; O:E ratio of mortality and
      morbidity were 0.47 and 0.85 in these patients. CONCLUSION: POSSUM and P-POSSUM
      are accurate tools for predicting morbidity and mortality respectively in EP
      patients. Though they may sometime over or under predict morbidity as well as
      mortality.

PMID- 22145059
TI  - Pattern of respiratory diseases seen among adults in an emergency room in a
      resource-poor nation health facility.
AB  - INTRODUCTION: There is a paucity of information on utilisation of emergency
      medical services in Nigeria. This study was conducted to determine the pattern of
      respiratory diseases seen among adults in an emergency room(ER) and their
      mortality within twenty- four hours in a health facility in Nigeria. METHODS: We
      carried out a retrospective study on adult patients that presented with
      respiratory condition from November 2004 to December 2010 at the emergency room
      of Federal Medical Centre Ido-Ekiti, south western, Nigeria. RESULTS: A total of
      3671 cases were seen, 368 were respiratory cases accounting for 10.2 % of the
      total emergency room visitations. The male to female patients ratio was 1.2:1 and
      their mean was 49 9 +/- 20.3 years. Pneumonia (34.5%) was the most common cases
      seen in the ER, followed PTB (29.4%), acute asthma (24.5%) , acute exacerbation
      of COPD (10.3%), upper airway tract obstruction and malignant pleural effusion
      were 0.5% respectively. Fourteen of the PTB cases (3.8%) were complicated by cor
      pulmonale, 9(2.5%) by pleural effusion, 4(1.1%) by massive haemoptysis and
      2(0.5%) by pneumothorax. Twenty-four hours mortality was 7.4% and 44.4% of the
      death was due to PTB, 37.0% was due to pneumonia and 14.8% due to acute asthma
      attack. The overall mortalities also had a bimodal age group distribution as the
      highest death was recorded in ages 30-39 and >= 70 years. CONCLUSION: Pneumonia
      and PTB were the leading respiratory diseases among adults causing of emergency
      room visit and early mortality in this health facility in Nigeria.

PMID- 22145060
TI  - [Hodgkin's disease and secondary colon cancer: report of a case].

PMID- 22145061
TI  - Health effects of agrochemicals among farm workers in commercial farms of Kwekwe
      district, Zimbabwe.
AB  - INTRODUCTION: Farm workers are at a very high risk of occupational diseases due
      to exposure to pesticides resulting from inadequate education, training and
      safety systems. The farm worker spends a lot of time exposed to these harmful
      agrochemicals. Numerous acute cases with symptoms typical of agrochemical
      exposure were reported from the commercial farms. We assessed the health effects
      of agrochemicals in farm workers in commercial farms of Kwekwe District
      (Zimbabwe), in 2006. METHODS: An analytical cross sectional study was conducted
      amongst a sample of 246 farm workers who handled agrochemicals when discharging
      their duties in the commercial farms. Plasma cholinesterase activity in blood
      specimens obtained from farm workers was measured using spectrophotometry to
      establish levels of poisoning by organophosphate and/or carbamates. Information
      on the knowledge, attitudes and practices of farm workers on agrochemicals use
      was collected using a pre-tested interviewer administered questionnaire.
      Bivariate and multivariate analyses were conducted to determine factors that were
      associated with abnormal cholinesterase activity. RESULTS: The prevalence of
      organophosphate poisoning, indicated by cholinesterase activity of 75% or less,
      was 24.1%. The median period of exposure to agrochemicals was 3 years (Q(1):=1
      year, Q(3):=7 years). Ninety eight (41.5%) farm workers knew the triangle colour
      code for the most dangerous agrochemicals. Not being provided with personal
      protective equipment (OR 2.00; 95% CI: 1.07 - 3.68) and lack of knowledge of the
      triangle colour code for most dangerous agrochemicals (OR 2.02; 95% CI: 1.02 -
      4.03) were significantly associated with abnormal cholinesterase activity.
      CONCLUSION: There was organophosphate poisoning in the commercial farms. Factors
      that were significantly associated with the poisoning were lack of protective
      clothing and lack of knowledge of the triangle colour code for most dangerous
      agrochemicals. We recommended intensive health education and training of farm
      workers on the use of agrochemicals, provision of adequate and proper personal
      protective equipment as mitigation measures to this problem.

PMID- 22145062
TI  - Using giant African pouched rats to detect tuberculosis in human sputum samples:
      2010 findings.
AB  - Giant African pouched rats previously have detected tuberculosis (TB) in human
      sputum samples in which the presence of TB was not initially detected by smear
      microscopy. Operant conditioning principles were used to train these rats to
      indicate TB-positive samples. In 2010, rats trained in this way evaluated 26,665
      sputum samples from 12,329 patients. Microscopy performed at DOTS centers found
      1,671 (13.6%) of these patients to be TB-positive. Detection rats identified 716
      additional TB-positive patients, a 42.8% increase in new-case detection. These
      previously unreported data, which extend to over 20,000 the number of patients
      evaluated by pouched rats in simulated second-line screening, suggest that the
      rats can be highly valuable in that capacity.

PMID- 22145063
TI  - Predictors of malignancy in pancreatic head mass: a prospective study.
AB  - INTRODUCTION: The objective of the study was to identify the predictive factors
      for malignancy in pancreatic head mass as a primary outcome and assess the value
      of CA 19-9 as a diagnostic tool for malignancy as a secondary outcome. METHODS: A
      prospective study of patients presented with pancreatic head mass was conducted
      in a tertiary care referral hospital, Manipal, India from May 2006 to November
      2008. The study population was divided into malignant and benign groups based on
      the final histopathology report. A univariate and multivariate analysis of
      potential predictive factors for malignancy were conducted. RESULTS: A total of
      102 patients with pancreatic head mass were included in the study after
      fulfilling the inclusion/exclusion criteria. 78 were malignant and 24 were
      benign. There was significant weight loss (p<0.001) and high mean bilirubin
      levels (p=0.002) in the malignant group. Mean CA 19-9 was significantly higher in
      the malignant group (290.7 vs. 30.3 U/ml; p<0.001). Sensitivity and specificity
      of CA 19-9 for detecting malignancy in pancreatic head mass at a cut off of 35
      U/ml was 86% and 79% respectively. CA 19-9 positivity rate was higher with
      increasing cut off values of 100, 200 and 300 U/ml but such high levels occurred
      in fewer patients. All the non-jaundiced patients (100%) with raised CA 19-9
      levels were found to be malignant compared to 86% malignancy in jaundiced
      patients. In multivariate analysis, a combination of weight loss>10% of body
      weight and bilirubin>3 mg/dl and CA 19-9>35 U/ml had specificity and positive
      predictive value of 100% for predicting malignancy in pancreatic head mass.
      CONCLUSION: The presence of weight loss and jaundice and raised CA 19-9 levels
      together in a patient with pancreatic head mass can be predictive of malignancy.
      A very high CA 19-9 level can be an indicator of malignancy in a pancreatic head
      mass. A raised CA 19-9 level may be more predictive of malignancy in non
      jaundiced patients than in jaundiced patients.

PMID- 22145064
TI  - Nail patella syndrome: a rare cause of renal failure in a young adult.
AB  - Nail Patella Syndrome (NPS) is a rare hereditary disease affecting multiple
      systems with predominant involvement of Kidney, Bones and Nails and Eyes. We
      report a case of NPS which presented as renal failure in a 22 year old male. The
      patient was admitted with decreased urine output and features of fluid overload
      and was being evaluated for renal failure. Physical examination revealed
      associated bony deformities which raised the suspicion of NPS as a possible
      etiology. This was confirmed by the radiological evaluation which showed the
      classical features of NPS. Though NPS is a rare clinical condition, physicians
      should complete knowledge about the components of NPS for appropriate diagnosis
      and for early detection of other systems involvement.

PMID- 22145065
TI  - Surveillance of acute flaccid paralysis in Akwa Ibom State, Nigeria 2004-2009.
AB  - INTRODUCTION: The last case of wild polio virus transmission occurred in Akwa
      Ibom state in October 2001; however, combination high routine immunization
      coverage with OPV, high quality AFP surveillance, mass immunization campaign in
      which two doses of potent oral polio vaccine is administered to eligible children
      and mop-up campaigns in areas with identified immunization or surveillance gaps
      has help the state in maintaining a free polio status for over ten years. This
      study was carried out to describe the characteristics of reported acute flaccid
      paralysis cases between 2004 and 2009, and to evaluate the performance of the
      acute flaccid paralysis surveillance system using indicators recommended by the
      World Health Organization. METHODS: A retrospective study was conducted among
      children, 0-15 years, by the World Health Organization (WHO) and Epidemiology
      unit of State Ministry of Health (SMOH), Uyo. The demographic characteristics and
      the results of isolation and identification of polio and other enteroviruses in
      stool samples sent to the WHO Polio Laboratory Ibadan for cases was analyzed.
      RESULTS: A total of 521 cases of AFP (270 males and 251 females) aged 0 month
      to=15 years were reported by the surveillance system between 2004 and 2009. Those
      below 5 years of age accounted for 82.5% of cases reported and investigated. Of
      the 521 cases investigated 512 (98.3%) received at least three doses of oral
      polio vaccine, while 9(1.7) never received any oral polio vaccine (zero-dose). In
      all 5.1% of the isolates were Sabin, 7.9% non polio enterovirus (NPEV) and 2.3%
      were classified by national expert committee as compatible with poliomyelitis.
      There was consistent and steady increase in three critical indicators; Non polio
      AFP rate in children <15 years from 4.5 to 6.4 per 100,000 population, proportion
      of AFP cases with 2 stool specimens collected within 14 days of onset of
      paralysis from 57% in 2005 to 91% in 2009 and proportion of Local Government
      Areas (Districts) meeting both core indicators from 23% in 2005 to 87% in 2009.
      The highest numbers of cases were seen in the months of March, May and September.
      CONCLUSION: This study showed high levels of surveillance performance with some
      challenges in reverse the cold chain system, the continuation and sustained AFP
      case detection, prompt investigation and response, improvement in the reserve
      cold chain system would achieve optimal standards recommended by WHO and might
      provide a good model for the eradication of poliomyelitis.

PMID- 22145066
TI  - Atopic dermatitis in Tunisian schoolchildren.
AB  - INTRODUCTION: The prevalence of atopic dermatitis (AD) is low in North Africa. We
      describe the epidemiology of this atopic condition among school children in
      Tunisia. METHODS: We conducted a Cross-sectional survey study of 5 to 6-year-old
      schoolchildren from 21 primary schools of Sfax. The diagnosis of AD was based on
      the U.K. Working Party diagnostic criteria. A questionnaire including these
      criteria and some risk factors of AD was issued to the children. All children
      were examined by one dermatologist. RESULTS: Among the 1617 examined children,
      ten had AD giving a one-year prevalence of 0.65%. The overall sex ratio was 2.33.
      The disease occurred before the age of 2 years in 3 children. Pure AD without
      concomitant respiratory allergies was noted in 3 cases. One first-degree family
      member with atopy was at least noted in seven children. The strongest associated
      factor was the presence of AD in at least one parent and maternal age at the time
      of the child birth. Nor breast-feeding neither environmental characteristics of
      the house did correlate with AD. CONCLUSION: The prevalence of AD in Tunisian
      schoolchildren is low but comparable to those of other developing countries.
      Family history of atopy and maternal age at the birth time was the most important
      associated factors.

PMID- 22145067
TI  - [Etiologies of exudative pleurisy: about 424 cases in Madagascar].

PMID- 22145068
TI  - Under-two child mortality according to maternal HIV status in Rwanda: assessing
      outcomes within the National PMTCT Program.
AB  - INTRODUCTION: We sought to compare risk of death among children aged under-2
      years born to HIV positive mother (HIV-exposed) and to HIV negative mother (HIV
      non-exposed), and identify determinants of under-2 mortality among the two groups
      in Rwanda. METHODS: In a stratified, two-stage cluster sampling design, we
      selected mother-child pairs using national Antenatal Care (ANC) registers.
      Household interview with each mother was conducted to capture socio-demographic
      data and information related to pregnancy, delivery and post-partum. Data were
      censored at the date of child death. Using Cox proportional hazard model, we
      compared the hazard of death among HIV-exposed children and HIV non-exposed
      children. RESULTS: Of 1,455 HIV-exposed children, 29 (2.0%; 95% CI: 1.3%-2.7%)
      died by 6 months compared to 18 children of the 1,565 HIV non-exposed children
      (1.2%; 95% CI: 0.6%-1.7%). By 9 months, cumulative risks of death were 3.0% (95%;
      CI: 2.2%-3.9%) and 1.3% (96%; CI: 0.7%-1.8%) among HIV-exposed and HIV non
      exposed children, respectively. By 2 years, the hazard of death among HIV-exposed
      children was more than 3 times higher (aHR:3.5; 95% CI: 1.8-6.9) among HIV
      exposed versus non-exposed children. Risk of death by 9-24 months of age was 50%
      lower among mothers who attended 4 or more antenatal care (ANC) visits (aHR: 0.5,
      95% CI: 0.3-0.9), and 26% lower among families who had more assets (aHR: 0.7, 95%
      CI: 0.5-1.0). CONCLUSION: Infant mortality was independent of perinatal HIV
      exposure among children by 6 months of age. However, HIV-exposed children were
      3.5 times more likely to die by 2 years. Fewer antenatal visits, lower household
      assets and maternal HIV seropositive status were associated with increased
      mortality by 9-24 months.

PMID- 22145069
TI  - Transfusion transmitted infections - a retrospective analysis from the National
      Blood Transfusion Service in Eritrea.
AB  - BACKGROUND: The emergence of transfusion transmitted infection (TTI) especially
      HIV/AIDS has created a huge obstacle in ensuring blood safety. To assess the
      situation in Eritrea, we carried out a retrospective study of 29,501 blood donors
      for the prevalence of TTI's i.e. HIV, HBV, HCV and Syphilis. METHODS: The study
      population included all donors who donated blood from January 2006 to November
      2009. The data was collected from the National Blood Transfusion Services (NTBS)
      of Eritrea and includes category of donor and result for TTI markers. RESULTS: A
      total of 29,501 units of blood were collected from 23,385(79%) voluntary blood
      donors and the rest 6,116(21%) units were collected from family replacement
      donors. The over all prevalence of TTI's were 3.8% with 3.5% in voluntary blood
      donors and 5.1% in family replacement donors. The sero-prevalence for TTI markers
      were 0.18% HIV, 2.58% HBV, 0.57% HCV and 0.49% Syphilis. CONCLUSION: In
      conclusion, even if the TTI prevalence rate among Eritrean blood donors is low,
      ensuring blood safety has a long way to go.

PMID- 22145070
TI  - [Percutaneous coronary angioplasty in women: clinical, procedural and prognostic
      features].

PMID- 22145071
TI  - Giant cystic lymphangioma of the small bowel mesentery: case report.
AB  - Cystic lymphangioma is an uncommon mesenteric tumor which is usually reported in
      children. We describe a case of a 12-years old girl who was admitted in our
      hospital with abdominal distension and pain. Physical examination showed an
      abdomino-pelvic mass. Preoperative studies including abdominal ultrasonography
      and computed tomography failed to determine the cause of the pain. Laparotomy
      found a giant cystic tumor of the small bowel mesentery. Histological studies
      confirm the diagnosis of cystic lymphangioma. Based on this case, a review of the
      literature is suggested.

PMID- 22145072
TI  - [Subcapsular hematoma of the liver complicating preeclampsia: about 6 cases].

PMID- 22145073
TI  - Ancient friends, revisited: New aspects on the important role of nuclear receptor
      signalling for skin physiology and for the treatment of skin diseases.

PMID- 22145074
TI  - Differentiation of banding patterns between Streptococcus mutans and
      Streptococcus sobrinus isolates in rep-PCR using ERIC primer.
AB  - BACKGROUND: Streptococcus mutans and Streptococcus sobrinus are considered to be
      important bacterial species in the initiation of human dental caries. Therefore,
      the establishment of a reliable genotyping method to distinguish S. mutans from
      S. sobrinus is of central importance. OBJECTIVE: We assessed the usefulness of
      repetitive extragenic palindromic polymerase chain reaction (rep-PCR) using ERIC
      primer banding patterns in differentiating S. mutans and S. sobrinus. DESIGN:
      Five S. mutans and two S. sobrinus prototype strains and 50 clinical isolates (38
      S. mutans serotype c, 4 S. sobrinus serotype d, and 8 S. sobrinus serotype g)
      were examined. The banding patterns of amplicons generated were compared among
      the prototype strains and clinical isolates, to find common bands that
      distinguish S. mutans and S. sobrinus. RESULTS: Multiple banding patterns were
      seen with all strains tested. The representative strains of S. mutans tested
      revealed six unique, strong bands at 2,000 bp, 1,700 bp, 1,400 bp, 1,100 bp, 850
      bp, and 250 bp, whereas S. sobrinus had seven strong bands at 2,000 bp, 1,800 bp,
      1,100 bp, 900 bp, 800 bp, 600 bp, and 550 bp. The band at 1,100 bp was the only
      band that was observed in both S. mutans and S. sobrinus. Furthermore, most
      clinical S. mutans isolates revealed identical banding patterns. All S. mutans
      had amplicons at 1,700 bp, 850 bp, and 250 bp, whereas those of S. sobrinus were
      at 1,100 bp, 900 bp, and 800 bp. CONCLUSIONS: These results indicate that using
      rep-PCR with the ERIC primers can distinguish between S. mutans and S. sobrinus.

PMID- 22145075
TI  - Optimization of a Cytochrome-P450-Monooxygenase-1A-Mediated EROD Assay in the
      Cape Hake Species Merluccius capensis and Merluccius paradoxus (Pisces).
AB  - Cytochrome P450 monooxygenase 1A (CYP1A) is induced by several planar toxic
      compounds, for example, polychlorinated biphenyls (PCBs) and the induction of
      this protein is often measured in terms of CYP1A-mediated 7-ethoxyresorufin-O
      deethylase (EROD) activity. This study was aimed at developing this assay in the
      Cape hake species Merluccius capensis and Merluccius paradoxus (considered one
      stock). Microsomal fractions were obtained from frozen fish liver samples by
      differential centrifugation. Fluorimetric and spectrophotometric analysis of the
      EROD assay resulted in the spectrophotometric (at 572 nm) detection method being
      selected, as this method resulted in a lower degree of variability and
      demonstrated higher reproducibility. The activity in the EROD assay was enhanced
      in the presence of NADPH, and the addition of dicumarol (phase II enzyme
      inhibitor) to the reaction mixtures prevented the underestimation of this assay
      by the inhibition of DT-diaphorase. In summary, an EROD assay was established for
      use in Cape hake species.

PMID- 22145076
TI  - Cellulases from thermophilic fungi: recent insights and biotechnological
      potential.
AB  - Thermophilic fungal cellulases are promising enzymes in protein engineering
      efforts aimed at optimizing industrial processes, such as biomass degradation and
      biofuel production. The cloning and expression in recent years of new cellulase
      genes from thermophilic fungi have led to a better understanding of cellulose
      degradation in these species. Moreover, crystal structures of thermophilic fungal
      cellulases are now available, providing insights into their function and
      stability. The present paper is focused on recent progress in cloning,
      expression, regulation, and structure of thermophilic fungal cellulases and the
      current research efforts to improve their properties for better use in
      biotechnological applications.

PMID- 22145078
TI  - "Wait and see" approach to the emergency department cardioversion of acute atrial
      fibrillation.
AB  - Objective. Acute atrial fibrillation often spontaneously resolves. This study
      aimed to investigate the outcomes and satisfaction of an evidence-based ED
      protocol employing a "wait and see" approach. Methods. A prospective
      observational cohort study of adult patients presenting to the Emergency
      Department with stable acute atrial fibrillation was performed. Patients were
      excluded if they were considered to be unstable, need hospitalization, or poor
      candidates for ED procedural sedation. Routine care was provided on the index
      visit, and suitable candidates were discharged and asked to return to the ED the
      following day for possible electrical cardioversion. Outcome measures included
      spontaneous reversion to sinus rhythm, success of cardioversion, length of stay,
      adverse event and return visits for AF within 30 days, and patient satisfaction.
      Results. Thirty five patient encounters were analysed over a 21-month period.
      Twenty two of the 35 patients (63%) had spontaneous resolution of atrial
      fibrillation upon presentation for potential cardioversion. All of the remaining
      patients underwent successful cardioversion to normal sinus rhythm without
      significant adverse events recorded. No patients required hospitalization. Three
      patients (9%) returned to the ED within 30 days for recurrence of atrial
      fibrillation. All patients were reported to be "very satisfied" with this
      approach. Conclusion. A "wait and see" approach to the ED electrical
      cardioversion of atrial fibrillation showed that almost two-thirds of patients
      had spontaneous resolution without requiring cardioversion or observation in the
      ED or hospital. All patients were successfully reverted to normal sinus rhythm
      and had a high degree of satisfaction.

PMID- 22145077
TI  - A Guided Tour of the Structural Biology of Gaucher Disease: Acid-beta-Glucosidase
      and Saposin C.
AB  - Mutations in both acid-beta-glucosidase (GCase) and saposin C lead to Gaucher
      disease, the most common lysosomal storage disorder. The past several years have
      seen an explosion of structural and biochemical information for these proteins,
      which have provided new insight into the biology and pathogenesis of Gaucher
      disease, as well as opportunities for new therapeutic directions. Nearly 20
      crystal structures of GCase are now available, from different heterologous
      sources, complexed with different ligands in the active site, in different
      glycosylation states, as well as one that harbors a prevalent disease-causing
      mutation, N370S. For saposin C, two NMR and 3 crystal structures have been
      solved, each with its unique snapshot. This review focuses on the details of
      these structures to highlight salient common and disparate features that
      contribute to our current state of knowledge of this complex orphan disease.

PMID- 22145079
TI  - Care of the critically ill emergency department patient with acute kidney injury.
AB  - Introduction. Acute Kidney Injury (AKI) is common and associated with significant
      mortality and complications. Exact data on the epidemiology of AKI in the
      Emergency Department (ED) are sparse. This review aims to summarise the key
      principles for managing AKI patients in the ED. Principal Findings. Timely
      resuscitation, goal-directed correction of fluid depletion and hypotension, and
      appropriate management of the underlying illness are essential in preventing or
      limiting AKI. There is no specific curative therapy for AKI. Key principles of
      secondary prevention are identification of patients with early AKI,
      discontinuation of nephrotoxic medication where possible, attention to fluid
      resuscitation, and awareness of the risks of contrast-induced nephropathy. In
      patients with advanced AKI, arrangements for renal replacement therapy need to be
      made before the onset of life-threatening uraemic complications. Conclusions.
      Research and guidelines regarding AKI in the ED are lacking and AKI practice from
      critical care departments should be adopted.

PMID- 22145080
TI  - Current pharmacological advances in the treatment of cardiac arrest.
AB  - Cardiac arrest is defined as the sudden cessation of spontaneous ventilation and
      circulation. Within 15 seconds of cardiac arrest, the patient loses
      consciousness, electroencephalogram becomes flat after 30 seconds, pupils dilate
      fully after 60 seconds, and cerebral damage takes place within 90-300 seconds. It
      is essential to act immediately as irreversible damage can occur in a short time.
      Cardiopulmonary resuscitation (CPR) is an attempt to restore spontaneous
      circulation through a broad range of interventions which are early
      defibrillation, high-quality and uninterrupted chest compressions, advanced
      airway interventions, and pharmacological interventions. Drugs should be
      considered only after initial shocks have been delivered (when indicated) and
      chest compressions and ventilation have been started. During cardiopulmonary
      resuscitation, no specific drug therapy has been shown to improve survival to
      hospital discharge after cardiac arrest, and only few drugs have a proven benefit
      for short-term survival. This paper reviews current pharmacological treatment of
      cardiac arrest. There are three groups of drugs relevant to the management of
      cardiac arrest: vasopressors, antiarrhythmics, and other drugs such as sodium
      bicarbonate, calcium, magnesium, atropine, fibrinolytic drugs, and
      corticosteroids.

PMID- 22145081
TI  - Glutamate-mediated primary somatosensory cortex excitability correlated with
      circulating copper and ceruloplasmin.
AB  - Objective. To verify whether markers of metal homeostasis are related to a
      magnetoencephalographic index representative of glutamate-mediated excitability
      of the primary somatosensory cortex. The index is identified as the source
      strength of the earliest component (M20) of the somatosensory magnetic fields
      (SEFs) evoked by right median nerve stimulation at wrist. Method. Thirty healthy
      right-handed subjects (51 +/- 22 years) were enrolled in the study. A source
      reconstruction algorithm was applied to assess the amount of synchronously
      activated neurons subtending the M20 and the following SEF component (M30), which
      is generated by two independent contributions of gabaergic and glutamatergic
      transmission. Serum copper, ceruloplasmin, iron, transferrin, transferrin
      saturation, and zinc levels were measured. Results. Total copper and
      ceruloplasmin negatively correlated with the M20 source strength. Conclusion.
      This pilot study suggests that higher level of body copper reserve, as marked by
      ceruloplasmin variations, parallels lower cortical glutamatergic responsiveness.

PMID- 22145082
TI  - Disturbed copper bioavailability in Alzheimer's disease.
AB  - Recent data from in vitro, animal, and human studies have shed new light on the
      positive roles of copper in many aspects of AD. Copper promotes the non
      amyloidogenic processing of APP and thereby lowers the Abeta production in cell
      culture systems, and it increases lifetime and decreases soluble amyloid
      production in APP transgenic mice. In a clinical trial with Alzheimer patients,
      the decline of Abeta levels in CSF, which is a diagnostic marker, is diminished
      in the verum group (8 mg copper/day), indicating a beneficial effect of the
      copper treatment. These observations are in line with the benefit of treatment
      with compounds aimed at normalizing metal levels in the brain, such as PBT2. The
      data reviewed here demonstrate that there is an apparent disturbance in metal
      homeostasis in AD. More research is urgently needed to understand how this
      disturbance can be addressed therapeutically.

PMID- 22145083
TI  - Evidence for Elevated Cerebrospinal Fluid ERK1/2 Levels in Alzheimer Dementia.
AB  - Cerebrospinal fluid (CSF) samples from 33 patients with Alzheimer dementia (AD),
      21 patients with mild cognitive impairment who converted to AD during followup
      (MCI-AD), 25 patients with stable mild cognitive impairment (MCI-stable), and 16
      nondemented subjects (ND) were analyzed with a chemiluminescence immunoassay to
      assess the levels of the mitogen-activated protein kinase ERK1/2 (extracellular
      signal-regulated kinase 1/2). The results were evaluated in relation to total Tau
      (tTau), phosphorylated Tau (pTau), and beta-amyloid 42 peptide (Abeta42). CSF
      ERK1/2 was significantly increased in the AD group as compared to stable MCI
      patients and the ND group. Western blot analysis of a pooled cerebrospinal fluid
      sample revealed that both isoforms, ERK1 and ERK2, and low amounts of doubly
      phosphorylated ERK2 were detectable. As a predictive diagnostic AD biomarker, CSF
      ERK1/2 was inferior to tTau, pTau, and Abeta42.

PMID- 22145084
TI  - A minimally invasive technique for percutaneous lumbar facet augmentation:
      Technical description of a novel device.
AB  - BACKGROUND: We describe a new posterior dynamic stabilizing system that can be
      used to augment the mechanics of the degenerating lumbar segment. The mechanism
      of this system differs from other previously described surgical techniques that
      have been designed to augment lumbar biomechanics. The implant and technique we
      describe is an extension-limiting one, and it is designed to support and cushion
      the facet complex. Furthermore, it is inserted through an entirely percutaneous
      technique. The purpose of this technical note is to demonstrate a novel posterior
      surgical approach for the treatment of lumbar degenerative. METHODS: This report
      describes a novel, percutaneously placed, posterior dynamic stabilization system
      as an alternative option to treat lumbar degenerative disk disease with and
      without lumbar spinal stenosis. The system does not require a midline soft-tissue
      dissection, nor subperiosteal dissection, and is a truly minimally invasive means
      for posterior augmentation of the functional facet complex. This system can be
      implanted as a stand-alone procedure or in conjunction with decompression
      procedures. RESULTS: One-year clinical results in nine individual patients, all
      treated for degenerative disease of the lower lumbar spine, are presented.
      CONCLUSIONS: This novel technique allows for percutaneous posterior dynamic
      stabilization of the lumbar facet complex. The use of this procedure may allow a
      less invasive alternative to traditional approaches to the lumbar spine as well
      as an alternative to other newly developed posterior dynamic stabilization
      systems.

PMID- 22145085
TI  - Non-operative management is superior to surgical stabilization in spine injury
      patients with complete neurological deficits: A perspective study from a
      developing world country, Pakistan.
AB  - BACKGROUND: Surgical stabilization of injured spine in patients with complete
      spinal cord injury is a common practice despite the lack of strong evidence
      supporting it. The aim of this study is to compare clinical outcomes and cost
      effectiveness of surgical stabilization versus conservative management of spinal
      injury in patients with complete deficits, essentially from a developing
      country's point of view. METHODS: A detailed analysis of patients with traumatic
      spine injury and complete deficits admitted at the Aga Khan University Hospital,
      Pakistan, from January 2004 till January 2010 was carried out. All patients
      presenting within 14 days of injury were divided in two groups, those who
      underwent stabilization procedures and those who were managed non-operatively.
      The two groups were compared with the endpoints being time to rehabilitation,
      length of hospital stay, 30 day morbidity/mortality, cost of treatment, and
      status at follow up. RESULTS: Fifty-four patients fulfilled the inclusion
      criteria and half of these were operated. On comparing endpoints, patients in the
      operative group took longer time to rehabilitation (P-value = 0.002); had longer
      hospital stay (P-value = 0.006) which included longer length of stay in special
      care unit (P-value = 0.002) as well as intensive care unit (P-value = 0.004); and
      were associated with more complications, especially those related to infections
      (P-value = 0.002). The mean cost of treatment was also significantly higher in
      the operative group (USD 6,500) as compared to non-operative group (USD 1490) (P
      value < 0.001). CONCLUSION: We recommend that patients with complete SCI should
      be managed non-operatively with a provision of surgery only if their
      rehabilitation is impeded due to pain or deformity.

PMID- 22145086
TI  - Slack brain in meningioma surgery through lateral supraorbital approach.
AB  - BACKGROUND: Surgery of skull base meningiomas by the lateral supraorbital (LSO)
      approach requires relaxed brain. Therefore, we assessed combined effects of the
      elements of neuroanesthesia on neurosurgical conditions during craniotomy.
      METHODS: The anesthesiological and surgical charts of 66 olfactory groove, 73
      anterior clinoidal, and 52 tuberculum sellae meningioma patients operated on by
      the senior author (J.H.) at the Department of Neurosurgery of Helsinki University
      Central Hospital, Helsinki, Finland, between September 1997 and August 2010, were
      retrospectively analyzed. RESULTS: One-hundred fifty-four (82%) patients had good
      surgical conditions, and this was achieved by (1) elevating the head 20 cm above
      the cardiac level in all patients with only slightly lateral turn or neck
      flexion, (2) administering mannitol preoperatively in medium or large meningiomas
      (n = 60), (3) maintaining anesthesia with propofol infusion (n = 46) or volatile
      anesthetics (n = 107) also in patients with large tumors (n = 37), and (4)
      controlling intraoperative hemodynamics. Brain relaxation was satisfactory in 18
      (10%) and poor in 15 (8%) patients. The median intraoperative blood loss was 200
      (range, 0-2000) ml. Only 9% of patients received red blood cell transfusion. The
      median time to extubation was 18 (range, 8-105) min after surgery. Extubation
      time correlated with the patients' preoperative clinical status and the size of
      tumor but not with the modality of anesthesia. CONCLUSIONS: Slack brain during
      the LSO approach is achieved by correct patient positioning, preoperative
      mannitol, either by propofol or in small tumors inhaled anesthetics, and
      optimizing cerebral perfusion pressure. Under these circumstances, intraoperative
      brain swelling is prevented, bleeding is minimal, and no blood transfusions are
      needed.

PMID- 22145087
TI  - Closing the gap between research techniques and clinical practice in the
      treatment of dementia.

PMID- 22145088
TI  - Posterior communicating artery aneurysm rupture mimicking apoplexy.
AB  - BACKGROUND: Cerebral aneurysm rupture can lead to devastating neurological
      complications and present a complex problem to treat. We report a unique case of
      a ruptured posterior communicating artery (PCoA) aneurysm presenting with sudden
      and complete vision loss. CASE DESCRIPTION: A 39-year-old man presented with the
      acute onset of severe headache and complete bilateral vision loss. The patient
      described headaches for several months prior to presentation. However, prior to
      the day of presentation, he had no visual disturbance. A CT angiogram (CTA) and
      magnetic resonance imaging (MRI) of the brain revealed a 1.6-cm, non-contrast
      enhancing suprasellar mass, eccentric to the left side, consistent with
      hemorrhagic mass. There was no obvious aneurysm or vascular malformation. The
      sella tursica was normal in appearance. The patient was taken for an immediate
      endoscopic endonasal transtuberculum approach for optic nerve decompression.
      Hematoma without an associated tumor was encountered and partially evacuated
      before aborting with resultant partial improvement in vision. A subsequent
      cerebral angiogram revealed an irregularly shaped, postero-laterally pointing,
      2.5-mm left PCoA aneurysm. The patient was then taken for open clipping of the
      ruptured aneurysm. A large, fibrinous capsule was found over the superolateral
      aspect of the aneurysm. The ruptured aneurysm was secured with clips and the
      surrounding hematoma was evacuated. CONCLUSION: In the immediate postoperative
      period, the patient regained vision in the nasal field of his right eye. This
      case illustrates a unique presentation of a ruptured PCoA aneurysm, and thus must
      be considered in the differential diagnosis of a suprasellar hemorrhage resulting
      in visual loss in absence of a recognizable associated tumor.

PMID- 22145089
TI  - Sternberg's canal as a cause of encephalocele within the lateral recess of the
      sphenoid sinus: A report of two cases.
AB  - BACKGROUND: Intrasphenoidal encephaloceles are extremely rare findings.
      Sternberg's canal is a lateral craniopharyngeal canal resulting from incomplete
      fusion of the greater wings of the sphenoid bone with the basisphenoid. It acts
      as a weak spot of the skull base, which may lead to develop a temporal lobe
      encephalocele protruding into the lateral recess of the sphenoid sinus (SS). CASE
      DESCRIPTION: We present two cases of intrasphenoidal encephalocele due to
      persistence of the lateral craniopharyngeal canal. The first case presented with
      cerebrospinal fluid (CSF) rhinorrhea and the second one was referred to the
      neurosurgical department with CSF rhinorrhea and meningitis. Radiological
      investigations consisted of computed tomography (CT) scan, CT cisternography and
      magnetic resonance images in both cases. These imaging studies identified a
      herniated temporal lobe through a bony defect which communicates the middle
      cranial fossa with the lateral recess of the SS. Both patients underwent a
      transcranial repair of the encephalocele because of the previous failure of the
      endoscopic surgery. There was no complication related to the surgical procedure
      and no recurrence of CSF leakage occurred 2 and 3 years after surgery,
      respectively. CONCLUSION: Encephalocele within the lateral recess of the SS is a
      rare entity which must be suspected in patients who present with spontaneous CSF
      rhinorrhea. Congenital intrasphenoidal encephaloceles, which are located medial
      to the foramen rotundum, seem to be due to persistence of the Sternberg's canal.
      Transcranial approach is a good option when a transnasal approach had failed
      previously.

PMID- 22145090
TI  - Small GTPases: The ultimate selfish genes?

PMID- 22145092
TI  - RhoGDI2 antagonizes ovarian carcinoma growth, invasion and metastasis.
AB  - Previous studies described functional roles for Rho GDP dissociation inhibitor 2
      (RhoGDI2) in bladder, gastric and breast cancers. However, only limited
      expression and no functional analyses have been done for RhoGDI2 in ovarian
      cancer. We determined RhoGDI2 protein expression and function in ovarian cancer.
      First, protein gel blot analysis was performed to determine the expression levels
      of RhoGDI2 in ovarian cells lines. RhoGDI2 but not RhoGDI1 protein expression
      levels varied widely in ovarian carcinoma cell lines, with elevated levels seen
      in Ras-transformed ovarian epithelial cells. Next, immunohistochemistry was
      performed to detect RhoGDI2 expression in patient samples of ovarian cysts and
      ovarian cancer with known histological subtype, stage, grade and outcome. RhoGDI2
      protein was significantly overexpressed in high-grade compared with low-grade
      ovarian cancers, correlated with histological subtype, and did not correlate with
      stage of ovarian cancer nor between carcinomas and benign cysts. Unexpectedly,
      stable suppression of RhoGDI2 protein expression in HeyA8 ovarian cancer cells
      increased anchorage-independent growth and Matrigel invasion in vitro and in tail
      vein lung colony metastatic growth in vivo. Finally, we found that RhoGDI2 stably
      associated preferentially with Rac1 and suppression of RhoGDI2 expression
      resulted in decreased Rac1 activity and Rac-associated JNK and p38
      mitogenactivated protein kinase signaling. RhoGDI2 antagonizes the invasive and
      metastatic phenotype of HeyA8 ovarian cancer cells. In summary, our results
      suggest significant cell context differences in RhoGDI2 function in cancer cell
      growth.

PMID- 22145091
TI  - Ubiquitination: Added complexity in Ras and Rho family GTPase function.
AB  - The regulation of the small GTPases leading to their membrane localization has
      long been attributed to processing of their C-terminal CAAX box. As deregulation
      of many of these GTPases have been implicated in cancer and other disorders,
      prenylation and methylation of this CAAX box has been studied in depth as a
      possibility for drug targeting, but unfortunately, to date no drug has proved
      clinically beneficial. However, these GTPases also undergo other modifications
      that may be important for their regulation. Ubiquitination has long been
      demonstrated to regulate the fate of numerous cellular proteins and recently it
      has become apparent that many GTPases, along with their GAPs, GeFs and GDis,
      undergo ubiquitination leading to a variety of fates such as re-localization or
      degradation. in this review we focus on the recent literature demonstrating that
      the regulation of small GTPases by ubiquitination, either directly or indirectly,
      plays a considerable role in controlling their function and that targeting these
      modifications could be important for disease treatment.

PMID- 22145093
TI  - Consequences of interrupted Rheb-to-AMPK feedback signaling in tuberous sclerosis
      complex and cancer.
AB  - Rheb is a small GTPase primarily known for activating mammalian target of
      rapamycin complex 1 (mTORC1) and promoting cell growth in response to insulin and
      nutrients (amino acids, glucose). Shortage of glucose activates adenosine 5'
      monophosphate-activated protein kinase (AMPK), which induces catabolic processes
      that produce ATP and suppresses energy-consuming anabolic reactions. As part of
      the latter response, AMPK activates the TSC1-TSC2 tumor suppressor complex, which
      in turn inhibits Rheb, thereby reducing mTORC1 activity and consequently
      suppressing protein synthesis. We recently identified an mTORC1-independent Rheb
      to-AMPK feedback signaling loop in Tsc2-null in vitro models of Tuberous
      Sclerosis Complex (TSC). In addition to activating AMPK, Rheb reduced the nuclear
      levels of the cyclin-dependent kinase inhibitor p27(KIP1) (p27). Importantly,
      Rheb-mediated repression of p27 correlated with activation of Cdk2 and cell
      proliferation, and with tumor formation by TSC cells. Considering that AMPK was
      previously reported to regulate stability and subcellular localization of p27, we
      hypothesize that Rheb regulates p27 in TSC cells by activating AMPK. This article
      discusses how Rheb-to-AMPK, and p27 signaling may impact on disease progression
      and treatment of TSC, including sporadic lymphangioleiomyomatosis (S-LAM) and
      malignancies.

PMID- 22145094
TI  - Activation of PAK by a bacterial type III effector EspG reveals alternative
      mechanisms of GTPase pathway regulation.
AB  - Small Rho GTPases regulate a diverse range of cellular behavior within a cell.
      Their ability to function as molecular switches in response to a bound nucleotide
      state allows them to regulate multiple dynamic processes, including cytoskeleton
      organization and cellular adhesion. Because the activation of downstream Rho
      GTPase signaling pathways relies on conserved structural features of target
      effector proteins (i.e., CRIB domain), these pathways are particularly vulnerable
      to microbial pathogenic attack. Here, we discuss new findings for how the
      bacterial virulence factor EspG from EHEC O157:H7 exploits a CRIB-independent
      activation mechanism of the Rho GTPase effector PAK. We also compare this
      mechanism to that of EHEC EspFU, a bacterial virulence factor that directly
      activates N-WASP. While both virulence factors break the inhibitory interaction
      between the autoinhibitory and activity-bearing domains of PAK or WASP, the
      underlying mechanics are very distinct from endogenous Cdc42/Rac GTPase
      regulation. The ability of bacterial proteins to identify novel regulatory
      principles of host signaling enzymes highlights the multi-level nature of protein
      activation, and makes them effective tools to study mammalian Rho GTPase
      signaling pathways.

PMID- 22145095
TI  - A Rab-based view of membrane traffic in the ciliate Tetrahymena thermophila.
AB  - Biologists have long recognized that some single-celled organisms show striking
      morphological and behavioral complexity, and details of the genetic underpinnings
      can be mined from the trove of newly-sequenced genomes. Ciliates, among which
      Tetrahymena thermophila and Paramecium tetraurelia have received most attention,
      provide clear examples of a lineage in which, as in animal cells, the core
      pathways of membrane traffic have undergone dramatic expansion and elaboration to
      facilitate multiple modes of exocytosis and endocytosis. Recent surveys of the
      Rab GTPases in T. thermophila, including analysis of a large set of GFP-tagged
      copies, provide a new set of compartmental markers for this lineage, as well as
      striking views of membrane dynamics in these cells. In addition, phylogenetic
      analysis of the Tetrahymena Rabs suggests that different eukaryotic lineages may
      have independently evolved some functionally similar pathways.

PMID- 22145096
TI  - Uniform auxin triggers the Rho GTPase-dependent formation of interdigitation
      patterns in pavement cells.
AB  - The investigation of Rho-family GTPases has uncovered mechanisms for
      spatiotemporal control of cellular processes such as cell polarization, movement,
      morphogenesis and cell division. Now Rho GTPase plays another leading role in the
      discovery of a new signaling mechanism for auxin, a multifunctional hormone that
      regulates pattern formation in plants. Arabidopsis leaf epidermal pavement cells
      (PCs) develop the puzzle-piece cell shape with interlocking lobes and
      indentations via interdigitated cellular growth.1 Through the ABP1 (Auxin Binding
      Protein 1) cell surface receptor, auxin coordinately activates 2 mutually
      exclusive Rho GTPase signaling pathways that are activated in the complementary
      lobing and indenting sides of adjacent cells: the ROP2 pathway for lobe formation
      and the ROP6 pathway for promoting indentation. This new signaling mechanism also
      involves ROP2-dependent polar accumulation of PIN1 in the plasma membrane, a
      member of the PIN auxin efflux carrier family that is critical for the formation
      of various developmental patterns including the PC interdigitation pattern. This
      Rho-dependent auxin signaling mechanism explains how interdigitated cellular
      growth is coordinated. In this extra view, we propose that the same mechanism can
      also explain how a uniform auxin signal initiates the formation of the
      interdigitated pattern.

PMID- 22145097
TI  - Autoantobodies activate small GTPase RhoA to modulate neurite outgrowth.
AB  - This review illustrates an example of adaptive immune responses (auto-antibodies)
      modulating growth/repair behavior of neurons in the disease context of Guillain
      Barre syndrome (GBS), which is a prototypic autoimmune, acute monophasic disorder
      of the peripheral nerves that is the commonest cause of acute flaccid paralysis
      worldwide. Anti-ganglioside antibodies (Abs) are the most commonly recognized
      autoimmune markers in all forms of GBS and these Abs are associated with poor
      recovery. Extent of axonal injury and failure of axonal regeneration are critical
      determinants of recovery after GBS. In this clinical context, our group examined
      the hypothesis that anti-ganglioside Abs adversely affect axon regeneration after
      peripheral nerve injury. We show that anti-ganglioside Abs inhibit axon
      regeneration in preclinical cell culture and animal models. This inhibition is
      mediated by activation of small GTPase RhoA and its downstream effector Rho
      kinase (ROCK) by modulation of growth cone extension and associated neurite
      elongation in neuronal cultures. Our studies suggest that RhoA and ROCK are
      potential targets for development of novel therapeutic strategies to enhance
      nerve repair.

PMID- 22145098
TI  - FLIM-FRET imaging in vivo reveals 3D-environment spatially regulates RhoGTPase
      activity during cancer cell invasion.
AB  - Many conceptual advances in biology have been achieved by experimental studies
      using planar two-dimensional cell culture systems. Recent adaptations of
      molecular techniques to three-dimensional model systems are bridging the gap in
      our understanding of biological events in vitro and in vivo in the study of
      disease progression. Recently, in vitro studies using Forster resonance energy
      transfer (FRET) have shown that the prototypical RhoGTPases Cdc42, Rac and RhoA
      are temporally and spatially synchronized during cell migration, with initial
      RhoA activity inducing protrusion prior to activation of Rac. This simultaneous
      FRET approach illustrates the tight control and dynamic regulation of RhoGTPase
      activity necessary for coordinated cell migration in vitro. Here, we discuss our
      recent work using FLIM-FRET analysis in a three-dimensional setting to reveal
      another layer of regulation in which RhoA activity is governed by the
      extracellular microenvironment. We demonstrate that RhoA is spatially regulated
      into discrete fractions of activity at the leading edge and rear of cells during
      invasion in vivo or within three-dimensional matrices. Significantly, this
      spatial regulation of RhoA was absent in two-dimensional in vitro settings. This
      distinct sub-cellular regulation of RhoA at the poles of invading cells in three
      dimensions sets a precedent that other RhoGTPases or signaling proteins may also
      be differentially regulated in a con-text-dependent manner during key biological
      processes such as invasion.

PMID- 22145099
TI  - BIM expression in treatment-naive cancers predicts responsiveness to kinase
      inhibitors.
AB  - Cancers with specific genetic mutations are susceptible to selective kinase
      inhibitors. However, there is a wide spectrum of benefit among cancers harboring
      the same sensitizing genetic mutations. Herein, we measured apoptotic rates among
      cell lines sharing the same driver oncogene following treatment with the
      corresponding kinase inhibitor. There was a wide range of kinase inhibitor
      induced apoptosis despite comparable inhibition of the target and associated
      downstream signaling pathways. Surprisingly, pretreatment RNA levels of the BH3
      only pro-apoptotic BIM strongly predicted the capacity of EGFR, HER2, and PI3K
      inhibitors to induce apoptosis in EGFR-mutant, HER2-amplified, and PIK3CA-mutant
      cancers, respectively, but BIM levels did not predict responsiveness to standard
      chemotherapies. Furthermore, BIM RNA levels in EGFR-mutant lung cancer specimens
      predicted response and duration of clinical benefit from EGFR inhibitors. These
      findings suggest assessment of BIM levels in treatment-naive tumor biopsies may
      indicate the degree of benefit from single-agent kinase inhibitors in multiple
      oncogene-addiction paradigms.

PMID- 22145101
TI  - Functions of lipids for enhancement of oral bioavailability of poorly water
      soluble drugs.
AB  - Lipid-based formulations encompass a diverse group of formulations with very
      different physical appearance, ranging from simple triglyceride vehicles to more
      sophisticated formulations such as self-emulsifying drug delivery systems
      (SEDDS). Lipid-based drug delivery systems may contain a broad range of oils,
      surfactants, and co-solvents. They represent one of the most popular approaches
      to overcome the absorption barriers and to improve the bioavailability of poorly
      water-soluble drugs. Diversity and versatility of pharmaceutical grade lipid
      excipients and drug formulations as well as their compatibility with liquid, semi
      solid and solid dosage forms make lipid systems most complex. Digestion of
      triglyceride lipids, physicochemical characteristics and solubilisation of lipid
      digestion products as well as intestinal permeability are some of the variable
      parameters of such formulations. Furthermore, among the factors affecting the
      bioavailability of the drug from lipid-based formulations are the digestion of
      lipid, the mean emulsion droplet diameter, the lipophilicity of the drug and the
      type of lipids. The solubility of the Active Pharmaceutical Ingredient in the
      Lipid System, the desorption/sorption isotherm and the digestibility of lipid
      vehicle are important issues to be considered for formulations of isotropic lipid
      formulations. This review also describes the fate of lipid formulations in the
      gut and the factors influencing the bioavailability from lipid-based
      formulations. Novel formulation systems and currently marketed products conclude
      this review.

PMID- 22145100
TI  - Oncogenic EGFR signaling activates an mTORC2-NF-kappaB pathway that promotes
      chemotherapy resistance.
AB  - Although it is known that mTOR complex 2 (mTORC2) functions upstream of Akt, the
      role of this protein kinase complex in cancer is not well understood. Through an
      integrated analysis of cell lines, in vivo models, and clinical samples, we
      demonstrate that mTORC2 is frequently activated in glioblastoma (GBM), the most
      common malignant primary brain tumor of adults. We show that the common
      activating epidermal growth factor receptor (EGFR) mutation (EGFRvIII) stimulates
      mTORC2 kinase activity, which is partially suppressed by PTEN. mTORC2 signaling
      promotes GBM growth and survival and activates NF-kappaB. Importantly, this
      mTORC2-NF-kappaB pathway renders GBM cells and tumors resistant to chemotherapy
      in a manner independent of Akt. These results highlight the critical role of
      mTORC2 in the pathogenesis of GBM, including through the activation of NF-kappaB
      downstream of mutant EGFR, leading to a previously unrecognized function in
      cancer chemotherapy resistance. These findings suggest that therapeutic
      strategies targeting mTORC2, alone or in combination with chemotherapy, will be
      effective in the treatment of cancer. SIGNIFICANCE: This study demonstrates that
      EGFRvIII-activated mTORC2 signaling promotes GBM proliferation, survival, and
      chemotherapy resistance through Akt-independent activation of NF-kappaB. These
      results highlight the role of mTORC2 as an integrator of two canonical signaling
      networks that are commonly altered in cancer, EGFR/phosphoinositide-3 kinase
      (PI3K) and NF-kappaB. These results also validate the importance of mTORC2 as a
      cancer target and provide new insights into its role in mediating chemotherapy
      resistance, suggesting new treatment strategies.

PMID- 22145102
TI  - Attenuation of cytotoxic natural product DNA intercalating agents by caffeine.
AB  - Many anti-tumor drugs function by intercalating into DNA. The xanthine alkaloid
      caffeine can also intercalate into DNA as well as form pi-pi molecular complexes
      with other planar alkaloids and anti-tumor drugs. The presence of caffeine could
      interfere with the intercalating anti-tumor drug by forming pi-pi molecular
      complexes with the drug, thereby blocking the planar aromatic drugs from
      intercalating into the DNA and ultimately lowering the toxicity of the drug to
      the cancer cells. The cytotoxic activities of several known DNA intercalators
      (berberine, camptothecin, chelerythrine, doxorubicin, ellipticine, and
      sanguinarine) on MCF-7 breast cancer cells, both with and without caffeine
      present (200 MUg/mL) were determined. Significant attenuation of the
      cytotoxicities by caffeine was found. Computational molecular modeling studies
      involving the intercalating anti-tumor drugs with caffeine were also carried out
      using density functional theory (DFT) and the recently developed M06 functional.
      Relatively strong pi-pi interaction energies between caffeine and the
      intercalators were found, suggesting an "interceptor" role of caffeine protecting
      the DNA from intercalation.

PMID- 22145103
TI  - Synthesis and Antimicrobial Evaluation of Dibenzo[b,e]oxepin-11(6H)-one O
      Benzoyloxime Derivatives.
AB  - A series of dibenzo[b,e]ox(thi)epin-11(6H)-one O-benzoyloximes has been
      synthesized and structurally elucidated by means of IR, (1)H-NMR, (13)C-NMR, MS,
      and elemental analysis. The newly developed compounds were screened at
      concentrations of 200-25 MUg/mL for their antibacterial activity against Gram+ve
      organisms such as Methicillin-Resistant Staphylococcus Aureus (MRSA), Gram-ve
      organisms such as Escherichia coli (E. coli), and at the same concentration range
      for their antifungal activity against fungal strain Aspergillus niger (A. niger)
      by the cup plate method. Ofloxacin and ketoconazole (10 MUg/mL) were used as
      reference standards for antibacterial and antifungal activity, respectively. The
      dibenzo[b,e]oxepines 6a-c and 6e-h showed low antimicrobial activity (MIC 125-200
      MUg/mL) compared to the reference substances, whereas a major improvement (MIC 50
      75 MUg/mL) was achieved with the synthesis of the corresponding bromomethyl
      derivative 6d. Moreover, replacement of oxygen by its bioisosteric sulfur led to
      isomeric dibenzo[b,e]thi-epine derivatives 6g,h which significantly exhibited
      higher antimicrobial activity (MIC 25-50 MUg/mL) against all tested culture
      strains used in the present study, demonstrating that a change of chemical class
      from dibenzo[b,e]oxepine to dibenzo[b,e]thiepine significantly improves the
      antimicrobial activity. Further variation, such as the oxidation of the thiepine
      sulfur to the corresponding isomeric dibenzo[b,e]thiepine 5,5-dioxide derivative
      9, comparatively failed to exhibit high activity (MIC 200 MUg/mL) against S.
      aureus, E. coli or A. niger.

PMID- 22145104
TI  - A facile synthesis and anticancer activity evaluation of spiro[thiazolidinone
      isatin] conjugates.
AB  - The synthesis and evaluation of the anticancer activity of 3'-aryl-5'-arylidene
      spiro[3H-indole-3,2'-thiazolidine]-2,4'(1H)-diones and spiro[3H-indole-3,2'-thi
      azolidine]-2,4'(1H)-dione-3'-alkanoic acid esters were described. The structure
      of the compounds was determined by (1)H and (13)C NMR and their in vitro
      anticancer activity was tested in the National Cancer Institute. Among the tested
      compounds, (5'Z)-5'-(benzylidene)-3'-(4-chlorophenyl)spiro[3H-indole-3,2'-thia
      zolidine]-2,4'(1H)-dione (IIa) and (5'Z)-3'-(4-chlorophenyl)-5'-[4-(1
      methylethyl)-benzylidene]spiro[3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione (IIb)
      were superior to other related compounds.

PMID- 22145105
TI  - Scavenger Activity Evaluation of the Clove Bud Essential Oil (Eugenia
      caryophyllus) and Eugenol Derivatives Employing ABTS Decolorization.
AB  - The essential oil (EO) of clove bud dried fruits from Eugenia caryophyllus was
      obtained by a conventional hydrodistillation process in an excellent yield (11.7
      %). Its chemical composition was analyzed by GC-MS, identifying eugenol as a main
      constituent (60.5%). Four eugenol-like molecules, gamma-diisoeugenol,
      hydroxymethyleugenol, dihydroeugenol and 1,3-dioxanylphenol, were synthesized
      using eugenol or isoeugenol as initial precursors under green chemistry
      protocols. To evaluate the possible antioxidant capacity of eugenol compounds
      including the clove bud EO, the Trolox(r) Equivalent Antioxidant Capacity value,
      obtained by the ABTS(+*) radical-cation discoloration method, was employed. The
      methodology was performed in a UV-Vis reader of 96-well microplates (dilution
      methodology), using well-known antioxidant agents (BHA, BHT and vitamin E) as
      reference compounds. It was found that the prepared eugenol derivatives had a
      more potent free radical scavenger activity than the reference compounds. In
      particular, the most active molecules, gamma-diisoeugenol and 1,3-dioxanylphenol,
      were ca. 3-fold more potent than vitamin E.

PMID- 22145106
TI  - Prediction of the Human EP1 Receptor Binding Site by Homology Modeling and
      Molecular Dynamics Simulation.
AB  - The prostanoid receptor EP1 is a G-protein-coupled receptor (GPCR) known to be
      involved in a variety of pathological disorders such as pain, fever and
      inflammation. These receptors are important drug targets, but design of subtype
      specific agonists and antagonists has been partially hampered by the absence of
      three-dimensional structures for these receptors. To understand the molecular
      interactions of the PGE2, an endogen ligand, with the EP1 receptor, a homology
      model of the human EP1 receptor (hEP1R) with all connecting loops was constructed
      from the 2.6 A resolution crystal structure (PDB code: 1L9H) of bovine rhodopsin.
      The initial model generated by MODELLER was subjected to molecular dynamics
      simulation to assess quality of the model. Also, a step by step ligand-supported
      model refinement was performed, including initial docking of PGE2 and iloprost in
      the putative binding site, followed by several rounds of energy minimizations and
      molecular dynamics simulations. Docking studies were performed for PGE2 and some
      other related compounds in the active site of the final hEP1 receptor model. The
      docking enabled us to identify key molecular interactions supported by the
      mutagenesis data. Also, the correlation of r(2)=0.81 was observed between the Ki
      values and the docking scores of 15 prostanoid compounds. The results obtained in
      this study may provide new insights toward understanding the active site
      conformation of the hEP1 receptor and can be used for the structure-based design
      of novel specific ligands.

PMID- 22145107
TI  - Identification of major degradation products of ketoconazole.
AB  - Analytical methods were developed for the identification of major degradation
      products of Ketoconazole, an antifungal agent. The stressed degradation of
      Ketoconazole drug substance was performed under acid, base, thermal, photo and
      oxidative stress conditions. The major degradation was observed under acid, base
      and oxidative stress conditions. The degradation study was performed on Inertsil
      ODS-3V, length 100 X diameter 4.6 mm, particle size 3 MUm column using gradient
      method. These degradants were identified by LC-MS technique.

PMID- 22145108
TI  - HPLC quantification of 4-nitrophenol and its conjugated metabolites from bile.
AB  - An isocratic ion pair RP-HPLC method with UV-Vis detection has been developed and
      validated for simultaneous analysis of 4-nitrophenol (PNP), 4-nitrophenyl beta
      glucuronide (PNP-G), and 4-nitrophenyl sulfate (PNP-S) in rat bile samples using
      4-ethylphenol (ETP) as internal standard. Chromatographic separation was achieved
      on a C(18) column by isocratic elution with a mobile phase consisted of methanol
      0.01 M citrate buffer pH 6.2 (47:53 v/v) containing 0.03 M TBAB. The flow rate
      was 1.0 ml min(-1), the detection was affected at 290 nm. Calibration plots were
      generated over the concentration range 1-100 MUM PNP, PNP-G, PNP-S with a common
      lower limit of quantification of 2.5 MUM. Intra- and inter-day precision and
      repeatability were determined at six different concentrations. Results obtained
      by application of the method for determination of PNP, PNP-G and PNP-S in bile
      fractions collected during intestinal perfusion of PNP in hyperglycemic rats are
      presented.

PMID- 22145109
TI  - Simple, Rapid and Validated LC Determination of Lopinavir in Rat Plasma and its
      Application in Pharmacokinetic Studies.
AB  - Lopinavir is a new specific and potent HIV-1 protease inhibitor. A simple and
      rapid Reverse Phase High-Performance Liquid Chromatographic method using UV
      detection was developed and validated for the analysis of lopinavir in rat plasma
      under isocratic conditions. The method involves a single step protein
      precipitation technique. The detector response was linear over the concentration
      range of 250 to 4000 ng mL (-1). High recovery ranging from 97.5 to 101.2 percent
      was obtained which precludes the use of internal standard. The developed method
      was validated as per standard guidelines. Validation of the developed method
      demonstrated accuracy, precision and selectivity of the proposed method. The drug
      was found to be stable under various processing and storage conditions. This
      rapid and cost-effective method was successfully applied in the estimation of
      lopinavir and determination of various pharmacokinetic parameters during post
      intravenous bolus administration of the drug in rats. The developed method can be
      suitably employed in preclinical pharmacokinetic evaluation of new formulations
      designed to improve the bioavailability of lopinavir.

PMID- 22145111
TI  - A Standard Protocol for the Calibration of Capillary Electrophoresis (CE)
      Equipment.
AB  - Calibration of complex analytical systems is always a difficult task.
      Nevertheless, a suitable approach has to be designed before the systems can be
      introduced into routine analysis. In literature, many methods have been described
      for the purpose of calibrating such systems, but only a few of them deal with
      capillary elctrophoresis. Here, we want to demonstrate a general approach to how
      the calibration of this type of analytical instrument becomes feasible.

PMID- 22145110
TI  - A Sensitive and Simple HPLC-UV Method for Trace Level Quantification of Ethyl p
      Toluenesulfonate and Methyl p-Toluenesulfonate, Two Potential Genotoxins in
      Active Pharmaceutical Ingredients.
AB  - A sensitive and simple HPLC/UV method has been developed and validated for the
      determination of two potential genotoxic impurities, namely methyl p
      toluenesulfonate (MPTS) and ethyl p-toluenesulfonate (EPTS) at trace levels in
      Pemetrexed sodium API. Applying the concept of threshold of toxicological concern
      (TTC), a limit of 3 ppm each for both genotoxins was calculated based on the
      maximum daily dose of API. A reversed phase LC method using UV detection was
      developed and validated. The method was found to be specific and selective for
      the application. The limit of detection (LOD) and limit of quantitation (LOQ) for
      both MPTS and EPTS was found to be 0.15 ppm (0.009 MUg mL(-1)) and 0.5 ppm (0.03
      MUg mL(-1)), respectively, with respect to sample concentration. The calibration
      curves of MPTS and EPTS were linear over the concentration range from LOQ to 6
      MUg/mL. The method was found to be specific, precise, linear and accurate and has
      been successfully applied to determine the two genotoxins in commercial batches
      of the API.

PMID- 22145112
TI  - High-Throughput NIR-Chemometric Method for Meloxicam Assay from Powder Blends for
      Tableting.
AB  - A near infrared (NIR) method able to directly quantify the active content in
      pharmaceutical powder blends used for manufacturing meloxicam tablets, without
      any sample preparation, was developed and fully validated. To develop calibration
      models for the assay of meloxicam in powder blends for tableting, the NIR
      reflectance spectra of different meloxicam powder blends prepared according to a
      calibration protocol was analysed using different preprocessing methods by
      partial last-square regression (PLS) and principal component regression (PCR).The
      best calibration model was found when partial last-square regression (PLS) was
      used as regression algorithm in association with Smoothing-Savitsky as pre
      processing spectrum method. The trueness, precision (repeatability and
      intermediate precision), accuracy, linearity and range of application of the
      developed NIR method were validated according to the International Conference of
      Harmonization (ICH) and Medicine European Agency (EMA) guidelines and found to be
      fit for its intended purpose.

PMID- 22145113
TI  - New Stability Indicating RP-HPLC Method for the Estimation of Cefpirome Sulphate
      in Bulk and Pharmaceutical Dosage Forms.
AB  - A simple stability indicating reversed-phase HPLC method was developed and
      subsequently validated for estimation of Cefpirome sulphate (CPS) present in
      pharmaceutical dosage forms. The proposed RP-HPLC method utilizes a LiChroCART
      Lichrosphere100, C18 RP column (250 mm * 4mm * 5 MUm) in an isocratic separation
      mode with mobile phase consisting of methanol and water in the proportion of
      50:50 % (v/v), at a flow rate 1ml/min, and the effluent was monitored at 270 nm.
      The retention time of CPS was 2.733 min and its formulation was exposed to
      acidic, alkaline, photolytic, thermal and oxidative stress conditions, and the
      stressed samples were analyzed by the proposed method. The described method was
      linear over a range of 0.5-200MUg/ml. The percentage recovery was 99.46. F-test
      and t-test at 95% confidence level were used to check the intermediate precision
      data obtained under different experimental setups; the calculated value was found
      to be less than the critical value.

PMID- 22145114
TI  - A Stability Indicating Method for the Determination of the Antioxidant Sodium
      Bisulfite in Pharmaceutical Formulation by RP-HPLC Technique.
AB  - A stability-indicating reversed-phase high-performance liquid chromatographic (RP
      HPLC) method was developed for the determination of sodium bisulfate (SB), an
      antioxidant, in injectable dosage form. The chromatographic separation was
      achieved on a Zorbax CN (250 mm * 4.6 mm, 5 MUm) column, with a mobile phase
      consisting of a buffer mixture of 0.03 M tetrabutylammonium hydrogen sulfate,
      0.01 M potassium dihydrogen orthophosphate, and acetonitrile at a ratio of 70:30
      (v/v) and a flow rate of 0.7 mL/min. The eluted compound was monitored at a
      wavelength of 215 nm using a UV detector. The method described herein separated
      sodium bisulfite from all other formulation components within a run time of 10
      min. The method also generated linear results over an SB concentration range of
      10 to 990 MUg/mL, and the limit of quantification was found to be 10 MUg/mL. The
      stability indicating capability of the method was established by performing
      forced degradation experiments. The RP-HPLC method that was developed was
      validated according to the International Conference on Harmonization (ICH)
      guidelines. This method was successfully applied in the quantitative
      determination of SB in a stability study of Amikacin sulfate injection. The
      procedure described herein is simple, selective, and reliable for routine quality
      control analysis as well as stability testing.

PMID- 22145115
TI  - Study on cytochrome p-450 dependent retinoic Acid metabolism and its inhibitors
      as potential agents for cancer therapy.
AB  - The relative lack of clinical success with conventional anticancer agents may be
      due in part to the traditional concept of cancer being a biological state rather
      than a dynamic process. Redefining cancer as a dynamic disease commencing with
      carcinogenesis introduces the possibility of chemoprevention. Retinoids offer the
      promise of a therapeutic option based on differentiation of premalignant as well
      as malignant cells. Research to date has concentrated on the use of exogenous
      retinoids in cancer. Although this research continues with new retinoid
      derivatives, an alternative approach to overcoming the drawbacks associated with
      exogenous retinoids has been to increase the levels of endogenous retinoic acid
      (RA) by inhibiting the cytochrome P450- mediated catabolism of RA using a novel
      class of agents known as retinoic acid metabolism blocking agents (RAMBAs which
      increase the level of endogenous retinoic acid (RA) within the tumor cells by
      blocking their metabolism. This approach presents several theoretic advantages.In
      the present study a wide range of established P-450 inhibitors has been screened
      to examine their inhibitory activity on all-trans-Retinoic acid (ATRA)
      metabolism. Forty-one known P450 inhibitors were tested for their inhibitory
      activity against RA metabolism. Most of them are nitrogen-containing compounds.
      The results showed that among these compounds only six compounds (N-benzyl-2
      phenylethanamine, itraconazole, chlorpromazine, 5-chloro-1,3-benzoxazol-2-amine,
      proadifen and furazolidone) showed inhibition of RA metabolism which was > 50%.
      Ketoconazole and liarozole were also screened as standard potent inhibitors in
      the same system and gave 87.5% and 89% inhibition, respectively. The results
      indicate that mostly azoles with substituents in positions other than the 1
      position on the ring are very weak inhibitors of RA metabolism. The most
      effective inhibitors (ketoconazole, itraconazole, bifonazole and clotrimazole)
      are 1-substituted and possess relatively large aromatic groups in the molecule. 1
      Substituted imidazoles bind to cytochrome P-450 with a very high affinity but
      substitution in the other position of the imidazole decreases the binding
      affinity.

PMID- 22145117
TI  - Induction of Biologically Active Flavonoids in Cell Cultures of Morus nigra and
      Testing their Hypoglycemic Efficacy.
AB  - The antidiabetic activity of both leaves and MJ-treated cell cultures of Morus
      nigra was evaluated after their oral administration to streptozotocin-induced
      diabetic rats. The antidiabetic activity of extracts from leaves given to
      streptozotocin (STZ)-diabetic rats for 10 days increased with increasing doses of
      leaves extract up to 500 mg/kg/day. The administration of 500 mg/kg/day of leaves
      extract reduced the concentration of glucose from 370 +/- 7.31 mg/dl (control) to
      154 +/- 6.27 mg/dl, and a significant increase in the insulin level from 11.3 +/-
      0.31 MUU/ml (control) to 14.6 +/- 0.43 MUU/ml was recorded. Cell suspension
      cultures were established from the young leaves of Morus nigra cultivated on
      modified MS medium supplemented with 2.0 mg/l 1-naphthaleneacetic acid (NAA), 0.2
      mg/l 6-(furfurylamino)purine (kinetin). The changes in cell weight and flavonoid
      content were monitored between day zero and 12. The linear increase in fresh
      weight was found to be parallel to flavonoids production. Cell cultures treated
      with 100 MUM methyl jasmonate for 24 hours showed a noticeable increase in level
      of flavonoids and significant and more effective hypoglycemic activity than that
      for extract from leaves. The major flavonoids were isolated by TLC and HPLC and
      identified as rutin, quercetin, Morusin and cyclomorusin by co-chromatography and
      mass spectrometry in comparison to samples of authentic reference compounds.

PMID- 22145116
TI  - Quinazolinobenzodiazepine Derivatives, Novobenzomalvins A-C: Fibronectin
      Expression Regulators from Aspergillus novofumigatus.
AB  - Three new quinazolinobenzodiazepine derivatives, novobenzomalvins A (1), B (2),
      and C (3), have been isolated as fibronectin expression regulators from
      Aspergillus novofumigatus CBS117520. The structures of 1 to 3 were established by
      spectroscopic and physicochemical analysis, and chemical investigation including
      the total synthesis of 1. Treatment with novo-benzomalvins A (1), B (2), C (3),
      and N-methylnovobenzomalvin A (5) increased the expression of fibronectin in
      normal human neonatal dermal fibroblast cells.

PMID- 22145118
TI  - A New Flavonoid C-Glycoside from Celtis australis L. and Celtis occidentalis L.
      Leaves and Potential Antioxidant and Cytotoxic Activities.
AB  - A major development over the past two decades has been the realization that free
      radical induced lipid peroxidation and DNA damage are associated with major
      health problems, e.g. cancer and ageing. Plant-derived antioxidants are
      increasingly found beneficial in protecting against these diseases. Celtis
      australis L. and Celtis occidentalis L. are two plants that have a variety of
      uses in folk medicine but have not been evaluated before for their antioxidant
      and cytotoxic properties. Therefore, the extracts of both plants' leaves were
      investigated for these activities, as well as isolation of the bioactive
      compounds responsible for the activities. Molecular structures of the compounds
      were elucidated by UV, HRESIMS, 1D ((1)H and (13)C) and 2D ((1)H-(13)C HSQC and
      (1)H-(13)C HMBC) NMR analyses. The ethanolic and aqueous extracts, n-butanol
      fractions and the isolated major compound were tested for their antioxidant
      activity using DPPH radical scavenging assay, xanthine oxidase-induced generation
      of superoxide radical and lipid peroxidation assay by thiobarbituric acid
      reactive substances (TBARS) method using rat tissue homogenates. Cytotoxic
      activities were studied using standard MTT assay. A novel flavonoid C
      triglycoside, 4'''-alpha-rhamnopyranosyl-2"-O-beta-d-galactopyranosylvitexin, was
      isolated from both plants' leaves, together with seven known flavonoids. The n
      butanol fractions and the major compound 2"-O-beta-galactopyranosylvitexin showed
      significant antioxidant activities, more pronounced than the tested standards BHT
      and dl-alpha-tocopherol in most tests. All extracts showed variable cytotoxic
      activities. This study provides strong evidence for the antioxidant and cytotoxic
      activities of the extracts of Celtis australis L. and Celtis occidentalis L.
      leaves, which were attributed to the polar n-butanol fractions and the major
      isolated flavonoid 2"-galactosylvitexin.

PMID- 22145120
TI  - Industry commitment to the science of safety.

PMID- 22145119
TI  - Non-inferiority and equivalence trials: Need for a standardized process.

PMID- 22145121
TI  - Implications of ICH-E5: Assessment of drug's sensitivity to ethnic factors and
      necessity of a bridging study for global drug development.
AB  - The ICH-E5 guideline provides a general framework for evaluating the potential
      impact of ethnic factors on the acceptability of foreign clinical data, with the
      underlying objective of minimizing duplication of clinical data, and it also
      describes the requirement of bridging studies for extrapolation of foreign
      clinical data to a new region. The ICH-E5 guideline brought great change in
      concept and strategy of global drug development for pharmaceutical companies. The
      procedures described in the ICH-E5 guideline have proved useful in the assessment
      of the ethnic sensitivity of a medicinal product that is to be introduced to a
      foreign region for registration purpose. Many companies are now developing
      various products based on ICH-E5 strategies and many successful cases will
      continuously appear within coming years.

PMID- 22145122
TI  - Quality of clinical trials: A moving target.
AB  - Quality of clinical trials depends on data integrity and subject protection.
      Globalization, outsourcing and increasing complexicity of clinical trials have
      made the target of achieving global quality challenging. The quality, as judged
      by regulatory inspections of the investigator sites, sponsors/contract research
      organizations and Institutional Review Board, has been of concern to the US Food
      and Drug Administration, as there has been hardly any change in frequency and
      nature of common deficiencies. To meet the regulatory expectations, the sponsors
      need to improve quality by developing systems with specific standards for each
      clinical trial process. The quality systems include: personnel roles and
      responsibilities, training, policies and procedures, quality assurance and
      auditing, document management, record retention, and reporting and corrective and
      preventive action. With an objective to improve quality, the FDA has planned new
      inspection approaches such as risk-based inspections, surveillance inspections,
      real-time oversight, and audit of sponsor quality systems. The FDA has partnered
      with Duke University for Clinical Trials Transformation Initiative, which will
      conduct research projects on design principles, data quality and quantity
      including monitoring, study start-up, and adverse event reporting. These recent
      initiatives will go a long way in improving quality of clinical trials.

PMID- 22145123
TI  - An evaluation of knowledge, attitude, and practice of adverse drug reaction
      reporting among prescribers at a tertiary care hospital.
AB  - OBJECTIVES: Spontaneous reporting is an important tool in pharmacovigilance.
      However, its success depends on cooperative and motivated prescribers. Under
      reporting of adverse drug reactions (ADRs) by prescribers is a common problem.
      The present study was undertaken to evaluate the knowledge, attitude, and
      practices (KAP) regarding ADR reporting among prescribers at the Civil Hospital,
      Ahmedabad, to get an insight into the causes of under-reporting of ADRs.
      MATERIALS AND METHODS: A pretested KAP questionnaire comprising of 15 questions
      (knowledge 6, attitude 5, and practice 4) was administered to 436 prescribers.
      The questionnaires were assessed for their completeness (maximum score 20) and
      the type of responses regarding ADR reporting. Microsoft Excel worksheet
      (Microsoft Office 2007) and Chi-Square test were used for statistical analysis.
      RESULTS: A total of 260 (61%) prescribers completed the questionnaire (mean score
      of completion 18.04). The response rate of resident doctors (70.7%) was better
      than consultants (34.5%) (P < 0.001). ADR reporting was considered important by
      97.3% of the respondents; primarily for improving patient safety (28.8%) and
      identifying new ADRs (24.6%). A majority of the respondents opined that they
      would like to report serious ADRs (56%). However, only 15% of the prescribers had
      reported ADRs previously. The reasons cited for this were lack of information on
      where (70%) and how (68%) to report and the lack of access to reporting forms
      (49.2%). Preferred methods for reporting were e-mail (56%) and personal
      communication (42%). CONCLUSION: The prescribers are aware of the ADRs and the
      importance of their reporting. However, under reporting and lack of knowledge
      about the reporting system are clearly evident. Creating awareness about ADR
      reporting and devising means to make it easy and convenient may aid in improving
      spontaneous reporting.

PMID- 22145124
TI  - Patient-reported outcomes: A new era in clinical research.
AB  - Now-a-days there is significant discussion about patient-reported outcomes (PRO)
      in medical world. The following article covers almost all the areas of PRO
      including-their importance, important concepts for understanding of PRO,
      significance, ideal properties, types, development and evaluation of PRO
      instruments. It is useful for physicians, pharmacists and patients for the
      assessment and improvement of the therapy.

PMID- 22145125
TI  - Survival analysis in clinical trials: Basics and must know areas.
AB  - Many clinical trials involve following patients for a long time. The primary
      event of interest in those studies is death, relapse, adverse drug reaction or
      development of a new disease. The follow-up time for the study may range from few
      weeks to many years. A different set of statistical procedures are employed to
      analyze the data, which involves time to event an analysis. It is a very useful
      tool in clinical research and provides invaluable information about an
      intervention. This article introduces the researcher to the different tools of
      survival analysis.

PMID- 22145126
TI  - Documents versus facts.

PMID- 22145127
TI  - Plagiarism: Pre-submission screening.

PMID- 22145128
TI  - Endocrine hypertension: Changing paradigm in the new millennium.

PMID- 22145129
TI  - From humans to giraffes: The evolution of hypertension and hormones.

PMID- 22145130
TI  - Neuro-endocrine regulation of blood pressure.
AB  - As our understanding of the underlying aetiology of hypertension is far from
      adequate, over 90% of patients with hypertension receive a diagnosis of essential
      hypertension. This non-specific diagnosis leads to suboptimal therapeutics and a
      major problem with non-compliance. Understanding the normal control of blood
      pressure (BP) is, hence, important for a better understanding of the disease.This
      review attempts to unravel the present understanding of BP control. The local
      mechanisms of BP control, the neural mechanisms, renal-endocrine mechanisms, and
      a variety of other hormones that have a bearing in normal BP control are
      discussed and the possible role in the pathophysiology is alluded to.

PMID- 22145131
TI  - Fetal origin of vascular aging.
AB  - Aging is increasingly regarded as an independent risk factor for development of
      cardiovascular diseases such as atherosclerosis and hypertension and their
      complications (e.g. MI and Stroke). It is well known that vascular disease evolve
      over decades with progressive accumulation of cellular and extracellular
      materials and many inflammatory processes. Metabolic syndrome, obesity and
      diabetes are conventionally recognized as risk factors for development of
      coronary vascular disease (CVD). These conditions are known to accelerate ageing
      process in general and vascular ageing in particular. Adverse events during
      intrauterine life may programme organ growth and favour disease later in life,
      popularly known as, 'Barker's Hypothesis'. The notion of fetal programming
      implies that during critical periods of prenatal growth, changes in the hormonal
      and nutritional milieu of the conceptus may alter the full expression of the
      fetal genome, leading to permanent effects on a range of physiological.

PMID- 22145133
TI  - Endocrine hypertension - Cushing's syndrome.
AB  - Hypertension is a major and frequent comorbid finding of Cushing's syndrome. This
      review discusses the etiology and pathophysiology of hypertension in Cushing's
      syndrome, while suggesting methods of management of this condition. It also
      provides an overview of diagnosis and management strategies in this disease.

PMID- 22145132
TI  - Mineralocorticoid hypertension.
AB  - Hypertension affects about 10 - 25% of the population and is an important risk
      factor for cardiovascular and renal disease. The renin-angiotensin system is
      frequently implicated in the pathophysiology of hypertension, be it primary or
      secondary. The prevalence of primary aldosteronism increases with the severity of
      hypertension, from 2% in patients with grade 1 hypertension to 20% among
      resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of
      disorders ranging from renin-producing pathologies (renin-secreting tumors,
      malignant hypertension, coarctation of aorta), aldosterone-producing pathologies
      (primary aldosteronism - Conns syndrome, familial hyperaldosteronism 1, 2, and
      3), non-aldosterone mineralocorticoid producing pathologies (apparent
      mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting
      tumors, ectopic adrenocorticotropic hormones (ACTH) syndrome, congenitalvadrenal
      hyperplasia), and drugs with mineraocorticoid activity (locorice, carbenoxole
      therapy) to glucocorticoid receptor resistance syndromes. Clinical presentation
      includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of
      plasma aldosterone concentraion to plasma renin activity remains the best
      screening tool. Bilateral adrenal venous sampling is the best diagnostic test
      coupled with a CT scan. Treatment is either surgical (adrenelectomy) for
      unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or
      bilateral disease. Medical therapy focuses on blood pressure control and
      correction of hypokalemia using a combination of anti-hypertensives (calcium
      channel blockers, angiotensin converting enzyme inhibitors, or angiotensin
      receptor blockers) and potassium-raising therapies (mineralcorticoid receptor
      antagonist or potassium sparing diuretics). Direct aldosterone synthetase
      antagonists represent a promising future therapy.

PMID- 22145134
TI  - Cushing's syndrome: Stepwise approach to diagnosis.
AB  - The projected prevalence of Cushing's syndrome (CS) inclusive of subclinical
      cases in the adult population ranges from 0.2-2% and it may no longer be
      considered as an orphan disease (2-3 cases/million/year). The recognition of CS
      by physicians is important for early diagnosis and treatment. Late-night salivary
      cortisol, dexamethasone suppressiontesti, or 24-h urine free cortisol are good
      screening tests. Positively screened cases need stepwise evaluation by an
      endocrinologist. This paper discusses the importance of screening for CS and
      suggests a stepwise diagnostic approach to a case of suspected hypercortisolism.

PMID- 22145135
TI  - Cushing's surgery: Role of the anesthesiologist.
AB  - Cushing's syndrome is a clinical situation, caused by excessive glucocorticoid
      level, resulting in several features such as central obesity, supraclavicular
      fat, "moon face," "buffalo hump," hyperglycemia, metabolic alkalosis,
      hypokalemia, poor wound healing, easy bruising, hypertension, proximal muscle
      weakness, thin extremities, skin thinning, menstrual irregularities, and purple
      striae. In the perioperative period, the anesthesiologist must deal with
      difficult ventilation and intubation, hemodynamic disturbances, volume overload
      and hypokalemia, glucose intolerance, and diabetes, maintaining the blood
      cortisol level and preventing the glucocorticoid deficiency. This syndrome is
      quite rare and its features make these patients very difficult to the
      anesthesiologist.

PMID- 22145136
TI  - Medical management of pheochromocytoma: Role of the endocrinologist.
AB  - Pheochromocytoma is a rare tumor arising from chromaffin cells in adrenal medulla
      or other paraganglia in the body, which may be associated with many genetic
      syndromes and mutation. The role of endocrinologist is in biochemical diagnosis
      of suspected cases; its anatomic and functional localization with the help of
      imaging like CT, MRI, and nuclear scanning; preoperative control of hypertension;
      and postoperative follow-up of cases that have undergone surgical resection.
      Familial and genetic screening of cases and their family is important to detect
      occult cases. Endocrinologist will also play a role in cases with malignant
      pheochromocytoma in assessment of metastasis, control, chemoradiotherapy, and
      follow-up.

PMID- 22145137
TI  - Implications and considerations during pheochromocytoma resection: A challenge to
      the anesthesiologist.
AB  - Pheochromocytoma is a rare catecholamine secreting tumor arising commonly from
      adrenal medulla. It has got multidimensional challenging aspects in spite of our
      improved understanding of its physiological and clinical behavior during surgical
      resection. This neuroendocrine tumor is associated with a most unpredictable and
      fluctuating clinical course during anesthesia and surgical intervention. The
      clinical difficulties and challenges increase manifold in patients with
      undiagnosed or accidental diagnosis of pheochromocytoma who present to the
      hospital for the treatment of some other disease or emergency. The most common
      manifestations of this clinical spectrum include hypertension, headache,
      palpitations, episodic sweating, and feeling of doom. The definite and only
      treatment for this rare tumor is surgical resection which itself is very
      challenging for an anesthesiologist. This article reviews the pre-operative
      evaluation, pharmacological preparation, intraoperative and post-operative
      management of patients with pheochromocytoma especially from anesthesiologist's
      perspectives.

PMID- 22145138
TI  - Natriuretic peptides: Diagnostic and therapeutic use.
AB  - Natriuretic peptides (NPs) are hormones which are mainly secreted from heart and
      have important natriuretic and kaliuretic properties. There are four different
      groups NPs identified till date [atrial natriuretic peptide (ANP), B-type
      natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and dendroaspis
      natriuretic peptide, a D-type natriuretic peptide (DNP)], each with its own
      characteristic functions. The N-terminal part of the prohormone of BNP, NT
      proBNP, is secreted alongside BNP and has been documented to have important
      diagnostic value in heart failure. NPs or their fragments have been subjected to
      scientific observation for their diagnostic value and this has yielded important
      epidemiological data for interpretation. However, little progress has been made
      in harnessing the therapeutic potential of these cardiac hormones.

PMID- 22145139
TI  - The thyroid hormone, parathyroid hormone and vitamin D associated hypertension.
AB  - Thyroid disorders and primary hyperparathyroidism have been known to be
      associated with increases in blood pressure. The hypertension related to
      hypothyroidism is a result of increased peripheral resistance, changes in renal
      hemodynamics, hormonal changes and obesity. Treatment of hypothyroidism with levo
      thyroxine replacement causes a decrease in blood pressure and an overall decline
      in cardiovascular risk. High blood pressure has also been noted in patients with
      subclinical hypothyroidism. Hyperthyroidism, on the other hand, is associated
      with systolic hypertension resulting from an expansion of the circulating blood
      volume and increase in stroke volume. Increased serum calcium levels associated
      with a primary increase in parathyroid hormone levels have been also associated
      with high blood pressure recordings. The mechanism for this is not clear but the
      theories include an increase in the activity of the renin-angiotensin-aldosterone
      system and vasoconstriction. Treatment of primary hyperparathyroidism by surgery
      results in a decline in blood pressure and a decrease in the plasma renin
      activity. Finally, this review also looks at more recent evidence linking
      hypovitaminosis D with cardiovascular risk factors, particularly hypertension,
      and the postulated mechanisms linking the two.

PMID- 22145140
TI  - Pediatric endocrine hypertension.
AB  - Endocrine causes of hypertension are rare in children and screening for endocrine
      hypertension in children should be carried out only after ruling out renal and
      renovascular causes. Excess levels and/or action of mineralocorticoids associated
      with low renin levels lead to childhood hypertension and this can be caused by
      various conditions which are discussed in detail in the article. Childhood
      pheochromocytomas are being increasingly diagnosed because of the improved
      application of genetic testing for familial syndromes associated with
      pheochromocytomas. Adolescents with polycystic ovarian syndrome (PCOS) can also
      have hypertension associated with their obese phenotype.

PMID- 22145141
TI  - Essential hypertension in adolescents and children: Recent advances in causative
      mechanisms.
AB  - Essential hypertension is the most common form of hypertension in adults, and it
      is recognized more often in adolescents than in younger children. It is well
      known that the probability of a diagnosis of essential hypertension increases
      with age from birth onward. The initiation of high blood pressure burden starts
      in childhood and continues through adolescence to persist in the remaining phases
      of life. The genesis of essential hypertension is likely to be multifactorial.
      Obesity, insulin resistance, activation of sympathetic nervous system, sodium
      homeostasis, renin-angiotensin system, vascular smooth muscle structure and
      reactivity, serum uric acid levels, genetic factors and fetal programming have
      been implicated in this disorder. In addition, erythrocyte sodium transport, the
      free calcium concentration in platelets and leukocytes, urine kallikrein
      excretion, and sympathetic nervous system receptors have also been investigated
      as other possible mechanisms. Obesity in children appears to be the lead
      contributor of essential hypertension prevalence in children and adolescents.
      Suggested mechanisms of obesity-related hypertension include insulin resistance,
      sodium retention, increased sympathetic nervous system activity, activation of
      renin-angiotensin-aldosterone, and altered vascular function. The
      etiopathogenesis of essential hypertension in children and adolescents appears to
      closely resemble that of adults. The minor variations seen could probably be due
      to the evolving nature of this condition. Many of the established mechanisms that
      are confirmed in adult population need to be replicated in the pediatric age
      group by means of definitive research for a better understanding of this
      condition in future.

PMID- 22145142
TI  - Management of diabetic hypertensives.
AB  - Hypertension occurs twice as commonly in diabetics than in comparable
      nondiabetics. Patients with both disorders have a markedly higher risk for
      premature microvascular and macrovascular complications. Aggressive control of
      blood pressure (BP) reduces both micro- and macrovascular complications. In
      diabetic hypertensives, angiotensin converting enzyme inhibitors (ACEIs) are the
      first line in management of hypertension, and can be replaced by angiotensin II
      receptor blockers (ARBs) if patients are intolerant of them. Recent studies
      suggest ARBs to be on par with ACEI in reducing both macro- and microvascular
      risks. Adding both these agents may have a beneficial effect on proteinuria, but
      no extra macrovascular risk reduction. Thiazides can also be used as first line
      drugs, but are better used along with ACEI/ARBs. Beta-blockers [especially if the
      patient has coronary artery disease] and calcium channel blockers are used as
      second line add-on drugs. Multidrug regimens are commonly needed in diabetic
      hypertensives. Achieving the target BP of <130/80 is the priority rather than the
      drug combination used in order to arrest and prevent the progression of macro-
      and microvascular complications in diabetic hypertensives.

PMID- 22145143
TI  - Hypertension in pregnancy: The endocrine and metabolic aspect.
AB  - Hypertension is the most common medical disorder complicating pregnancy. However,
      how pregnancy incites or aggravates hypertension remains unsolved despite decades
      of intensive research. Various endocrine and metabolic mechanisms have been
      postulated to contribute to the pathogenesis of hypertension in pregnancy.
      Understanding the endocrine aspect of the possible pathophysiological mechanism
      might open new vistas in prediction, prevention and management of this condition.

PMID- 22145144
TI  - Radiological imaging in endocrine hypertension.
AB  - While different generations of assays have played important role in elucidating
      causes of different endocrine disorders, radiological techniques are instrumental
      in localizing the pathology. This statement cannot be truer in any disease entity
      other than endocrine hypertension. This review makes an effort to highlight the
      role of different radiological modalities, especially ultrasonography, computed
      tomography and magnetic resonance imaging, in the evaluation of different causes
      of endocrine hypertension.

PMID- 22145145
TI  - The Screening India's Twin Epidemic: Study design and methodology (SITE-1).
AB  - OBJECTIVES: The recent years have seen a surge in the prevalence of both diabetes
      and hypertension. Significant demographic variations reported on the prevalence
      patterns of diabetes and hypertension in India establish a clear need for a
      nation-wide surveillance study. The Screening India's Twin Epidemic (SITE) study
      aimed at collecting information on the prevalence of diagnosed and undiagnosed
      diabetes and hypertension cases in outpatient settings in major Indian states to
      better understand disease management, as well as to estimate the extent of
      underlying risk factors. MATERIALS AND METHODS: During 2009-2010, SITE was
      conducted in eight states, in waves - one state at a time. It was planned to
      recruit about 2000 patients from 100 centers per wave. Each center enrolled the
      first 10 eligible patients (>=18 years of age, not pregnant, signed data release
      consent form, and ready to undergo screening tests) per day on two consecutive
      days. Patient demographics, medical history, and laboratory investigation results
      were collected and statistically interpreted. The protocol defined diabetes and
      hypertension as per the American Diabetes Association (ADA) and Seventh Report of
      the Joint National Committee on Prevention, Detection, Evaluation, and Treatment
      of High Blood Pressure (JNC 7) recommendations, respectively. RESULTS: After the
      first two pilot phases in Maharashtra and Delhi, the protocol was refined and the
      laboratory investigations were simplified to be further employed for all other
      states, namely, Tamil Nadu, West Bengal, Karnataka, Andhra Pradesh, Madhya
      Pradesh, and Gujarat. CONCLUSION: SITE's nation-wide approach will provide a real
      world perspective on diabetes and hypertension and its contributing risk factors.
      Results from the study will raise awareness on the need for early diagnosis and
      management of these diseases to reduce complications.

PMID- 22145146
TI  - Renin-angiotensin system activity in vitamin D deficient, obese individuals with
      hypertension: An urban Indian study.
AB  - BACKGROUND: Elevated renin-angiotensin-aldosterone system (RAAS) activity is an
      important mechanism in the development of hypertension. Both obesity and 25
      hydroxy vitamin D [25(OH)D] deficiency have been associated with hypertension and
      augmented renin-angiotensin system (RAS) activity. We tried to test the
      hypothesis that vitamin D deficiency and obesity are associated with increased
      RAS activity in Indian patients with hypertension. MATERIALS AND METHODS: Fifty
      newly detected hypertensive patients were screened. Patients with secondary
      hypertension, chronic kidney disease, or coronary artery disease were excluded.
      Patients underwent measurement of vitamin D and plasma renin and plasma
      aldosterone concentrations. They were divided into three groups according to
      their baseline body mass index (BMI; normal <25 kg/m(2), overweight 25-29.9
      kg/m(2) and obese >=30 kg/m(2)) and 25(OH)D levels (deficient <20 ng/ml,
      insufficient 20-29 ng/ml and optimal >=30 ng/ml). RESULTS: A total of 50
      (male:female - 32:18) patients were included, with a mean age of 49.5 +/- 7.8
      years, mean BMI of 28.3 +/- 3.4 kg/m(2) and a mean 25(OH)D concentration of 18.5
      +/- 6.4 ng/ml. Mean systolic blood pressure (SBP) was 162.4 +/- 20.2 mm Hg and
      mean diastolic blood pressure (DBP) was 100.2 +/- 11.2 mm Hg. All the three blood
      pressure parameters [SBP, DBP and mean arterial pressure (MAP)] were
      significantly higher among individuals with lower 25(OH)D levels. The P values
      for trends in SBP, DBP and MAP were 0.009, 0.01 and 0.007, respectively. Though
      all the three blood pressure parameters (SBP, DBP and MAP) were higher among
      individuals with higher BMIs, they were not achieving statistical significance.
      Increasing trends in PRA and PAC were noticed with lower 25(OH)D and higher BMI
      levels. CONCLUSION: Vitamin D deficiency and obesity are associated with
      stimulation of RAAS activity. Vitamin D supplementation along with weight loss
      may be studied as a therapeutic strategy to reduce tissue RAS activity in
      individualswith Vitamin D deficiency and obesity.

PMID- 22145147
TI  - Role of cortical sparing adrenalectomy and novel variant of mutation in patient
      with von Hippel-Lindau disease.
AB  - Neurofibromatosis type 1 is the most common phakomatoses and is inherited in
      autosomal dominant fashion with complete penetrance. Secondary hypertension is
      common in these patients due to various causes including adrenal tumors.
      Pheochromocytoma is a rare catecholamine producing tumor seen in 0.5% to 5% of
      patients with neurofibromatosis. The combination of pheochromocytoma with
      neurofibromatosis is rarely reported in the literature. We recently encountered
      an elderly lady with this combination who successfully underwent adrenalectomy.
      We report the case for the uncommon occurrence and to highlight the relevant
      literature review about pheochromocytoma in neurofibromatosis.

PMID- 22145148
TI  - Neurofibromatosis 1 with pheochromocytoma.
AB  - Von Hippel-Lindau (VHL) disease includes a wide spectrum of highly vascular
      tumors like pheochromocytoma, cysts and adenomas of the pancreas and kidney,
      endolymphatic sac and renal cell carcinoma. Molecular analysis of the VHL gene is
      vital in these patients and their kindred. Neuroendocrine pancreatic tumors are
      rare and are known for their malignant and metastatic potential. We discuss an
      interesting case of a young lady who had a strong family history of central
      nervous system and spinal tumors. Our patient presented with recently detected
      severe hypertension. She was found to have elevated urinary normetanephrine
      levels; radiological imaging revealed bilateral pheochromocytomas with a
      pancreatic lesion. On genetic analysis, a variation, c.IVS 2 + 3 A > G, was found
      in the intronic region following exon 2 of the VHL gene. This variant appears
      novel. This patient underwent bilateral adrenalectomy (right total and left
      cortical sparing), distal pancreatectomy and splenectomy. Histology was
      diagnostic for pheochromocytoma with a neuroendocrine tumor of the pancreas. The
      postoperative period was uneventful. She was advised genetic screening of all her
      first-degree relatives.

PMID- 22145149
TI  - Inappropriate concomitant use of amlodipine and simvastatin: A report on its
      incidence in a primary care unit.

PMID- 22145153
TI  - A stannum-bismuth composite film electrode for simultaneous determination of
      zinc(II) and cadmium(II) using differential pulse anodic stripping voltammetry.
AB  - The development and use of 'green' electrode materials is extremely attractive
      for the routine use of disposable metal sensors. Bismuth is an environmentally
      friendly element and a bismuth film electrode was proposed as an alternative to
      mercury film electrodes. Compared with bismuth, stannum is a more
      'environmentally friendly' material. The stannum-bismuth composite film electrode
      prepared by the in situ electrodeposition of stannum and bismuth on the glassy
      carbon substrate is reported for the first time. Compared with bismuth film and
      stannum film electrodes, the stannum-bismuth composite film electrode revealed
      better electroanalytical performance, and can be used as a possible alternative
      electrode for electrochemical stripping analysis of trace heavy metals.

PMID- 22145154
TI  - Claiming space for an engaged anthropology: spatial inequality and social
      exclusion.
AB  - I use the concept of "engaged anthropology" to frame a discussion of how
      "spatializing culture" uncovers systems of exclusion that are hidden or
      naturalized and thus rendered invisible to other methodological approaches.
      "Claiming Space for an Engaged Anthropology" is doubly meant: to claim more
      intellectual and professional space for engagement and to propose that
      anthropology include the dimension of space as a theoretical construct. I draw on
      three fieldwork examples to illustrate the value of the approach: (1) a Spanish
      American plaza, reclaimed from a Eurocentric past, for indigenous groups and
      contemporary cultural interpretation; (2) Moore Street Market, an enclosed Latino
      food market in Brooklyn, New York, reclaimed for a translocal set of social
      relations rather than a gentrified redevelopment project; (3) gated communities
      in Texas and New York and cooperatives in New York, reclaiming public space and
      confronting race and class segregation created by neoliberal enclosure and
      securitization.

PMID- 22145155
TI  - Who has time for Cejf? Postsocialist migration and slow coffee in neoliberal
      Chicago.
AB  - The official end to communism in Eastern Europe marked the onset of major
      migratory movements. Perhaps the most abrupt of these population shifts was the
      displacement of more than two million people in Yugoslavia's violent dissolution.
      Much of the existing literature on refugee migration has focused on victimization
      and citizenship claims. Alternatively, I draw on ethnographic research among
      Bosnian refugee-immigrants in Chicago to examine how a group of adult women
      migrants used one commodity - coffee - to manage and evaluate their
      displacements. The kind of slow-coffee drinking described here is informed by an
      ethics of consumption developed under Yugoslav socialism, nostalgias for pre
      Yugoslav Islam and pre-Ottoman Bosnia, and exposure to U.S. neoliberalism.
      Placing consumption at the center of analysis reveals the structural constraints
      of the postconflict period and brings to light refugees' active navigations of
      everyday life and society in their postsocialist present, lived out as refugees
      in the United States.

PMID- 22145156
TI  - [The inequalities of gender in terms of sexuality].

PMID- 22145157
TI  - [The construction of representations  of gender and homosexuality at school,  in
      the family and in the media].

PMID- 22145158
TI  - Shining new light on the brain.
AB  - Optogenetics - a new methodology that involves expression of light-responsive
      proteins in specific groups of neurons, which can then be activated with light -
      has only been around for six years, but some researchers are already using it to
      target big psychiatric questions. Michael Gross reports.

PMID- 22145159
TI  - The quantitative aspects of biology. Sten Grillner.

PMID- 22145160
TI  - Keratin and filaggrin expression in comedonal Darier's disease.

PMID- 22145161
TI  - A closer look at the spatial architecture of aphid clones.
AB  - Nearly 25 years ago, Ellstrand & Roose (1987) reviewed what was known at the time
      of the genetic structure of clonal plant species. What is the relationship
      between space and clonal fitness, they asked. What is the best way for a clone to
      grow within its ecological neighbourhood? The pot had been stirred 10 years
      previously by Janzen (1977), who pointed out how little we know about the
      population biology of clonal organisms like dandelions and aphids. He wondered
      whether, like good curries, outward appearances masked common ingredients.
      Because in no small part of the advent of molecular ecology, we know more about
      clonal life histories today, particularly in plants (van Dijk 2003; Vallejo-Marin
      et al. 2010). Surprisingly, studies of the spatial architecture of aphid clones
      have been comparably rare. In this issue of Molecular Ecology, Vantaux et al.
      characterize the finescale distribution of the black bean aphid (Aphis fabae) and
      in so doing, help to fill that gap. They describe a moderate degree of
      intermingling between aphid clones over a growing season--A. fabae clones are
      'sticky', but only a bit. By mixing, clones directly compete with each other as
      well. The results of Vantaux et al. (2011) will help to integrate evolutionary
      patterns in aphids with the appropriate ecological scales out of which those
      patterns emerge.

PMID- 22145162
TI  - Niche diversification follows key innovation in Antarctic fish radiation.
AB  - Antarctic notothenioid fishes provide a fascinating evolutionary laboratory for
      the study of adaptive radiation, as their diversification is linked to both
      isolation in an extreme environment and a key innovation that allows them to
      exploit it. In this issue of Molecular Ecology, Rutschmann et al. (2011) evaluate
      how dietary niche differences have evolved in notothenioids: rarely, or
      repeatedly in multiple lineages. The authors use stable isotopes to measure
      species' use of benthic vs. pelagic resources and map resource use onto a
      molecular phylogeny. Their findings indicate that pelagic diets have evolved in
      multiple lineages in at least two families, indicating that dietary niche
      diversification has occurred repeatedly and in parallel.

PMID- 22145163
TI  - Application of partial-filling capillary  electrophoresis using lectins and 
      glycosidases for the characterization of  oligosaccharides in a therapeutic
      antibody.
AB  - Oligosaccharides in therapeutic recombinant antibodies play important roles in
      regulation of various biological functions. To monitor the glycosylation profiles
      of antibody pharmaceuticals in the manufacturing process, a highly sensitive and
      specific method is required. We extended partial-filling techniques using lectins
      and exoglycosidases in capillary electrophoresis for the characterization of 8
      aminopylene-1,3,6-trisulfonic acid labeled N-linked oligosaccharides derived from
      the therapeutic antibody rituximab. In the lectin-filling method, Galb1-4GlcNAc
      specific Erythrina cristagali agglutinin, a1, 6-linked Fuc-specific Aleuria
      aurantia lectin and Neu5Aca2-3Gal-specific Maackia amurensis lectin were used.
      The oligosaccharides migrated through the lectin plug during separation; the
      changes in separation profiles were observed according to the interaction with
      the lectins. The glycosidase-filling method allowed rapid digestion as suggested
      by the electropherograms. Partial-filling CE methods can avoid tedious hands-on
      procedures such as overnight incubation and optimization reaction condition with
      lectins and exoglycosidases. Combination of these partial-filling capillary
      electrophoresis methods makes the characterization of oligosaccharide profiles of
      therapeutic antibodies easier and faster.

PMID- 22145164
TI  - Use of CE-SDS gel for characterization  of monoclonal antibody hinge region 
      clipping due to copper and high pH stress.
AB  - CE-SDS gel technique has been used extensively in the field of monoclonal
      antibody (mAb) as a tool for product purity, stability, and characterization. It
      offers many advantages over the traditional labor-intensive SDS-PAGE slab gel
      technology with respect to speed and resolution. Monoclonal antibodies are known
      to cleave in the hinge region due to extreme pH, high temperature and in the
      presence of metals, especially copper. This cleavage will impact the shelf
      lifetime of mAb product hence its quality. CESDS gel method using Beckman PA800
      with UV detection is used to characterize the effects of copper and other metals
      such as iron and zinc on mAb clipping. In addition, mAb integrity under high
      temperature and high pH stress conditions was also evaluated and the results
      clearly show that CE-SDS gel can distinguish clipping due to copper versus heat
      and/or high pH. The data presented illustrate the power of this simple CESDS gel
      technique in supporting the development of mAb from product quality and stability
      to the final product characterization.

PMID- 22145165
TI  - Innate immunity mechanisms.

PMID- 22145166
TI  - The Commission on Macroeconomics and Health: 10 years on.

PMID- 22145167
TI  - Current strategies for allergen-specific immunotherapy at its centenary.

PMID- 22145168
TI  - Gene expression analysis of amniotic fluid: new biomarkers and novel antenatal
      treatments.

PMID- 22145169
TI  - Exploring the neonatal salivary transcriptome: technical optimization and 
      clinical applications.

PMID- 22145170
TI  - Will HIPAA 5010 hurt? With the HIPAA 5010 deadline right around the corner, HMT
      asked select industry experts the following question: How will the adoption of
      HIPAA 5010 (federally mandated to take place by Jan. 1, 2012) affect practice
      profitability?

PMID- 22145171
TI  - Streamlining operations healthcare reporting: by automating manual processes with
      content transformation, healthcare facilities are better able to apply resources
      towards their ROI.

PMID- 22145172
TI  - Streamlining patient review: Morehead Memorial expands care-management program,
      ensuring appropriate patient care.

PMID- 22145173
TI  - Countercurrents from the West: "blue-eyed" Zen masters, Vipassana meditation, and
      Buddhist psychotherapy in contemporary Korea.
AB  - One surprising and yet relatively unknown aspect of contemporary Korean Buddhism
      is the significant influence of American and European Buddhism. Between 1989 and
      2009, South Koreans witnessed well-educated "blue-eyed" monastic residents via
      the Korean media, and the emergence of new bestsellers by authors like Thich Nhat
      Hahn and Jack Kornfield, written initially for Western audiences but since
      translated into Korean. The new teachings from the West have inspired a sudden
      growth of interest in vipassana meditation as an "alternative" to Kanhwa Son
      practice, and the emergence of a new academic field: Buddhist psychotherapy. This
      new wave of transnational influence from the West has changed not only the way
      Koreans practice Buddhism but also how they perceive Buddhist history and their
      own identities. In addition, the perceived "prestige" of Buddhism in the West has
      provided a new rhetorical strategy to defend Buddhism against other religions,
      particularly Korean evangelical Christianity.

PMID- 22145174
TI  - Student activism, mental health, and English-Canadian universities in the 1960s.
AB  - Student mental health services were created at many American universities during
      the interwar years in association with the mental hygiene movement of that era.
      In Canada, psychologists and psychiatrists became focused on the well-being of
      schoolchildren during this period, but services for university students were
      minimal or non-existent at most institutions until well after the Second World
      War. Influenced by American trends and in tune with rising public concern over
      the problems students were experiencing on Canada's burgeoning campuses, student
      organizations, in co-operation with the Canadian Mental Health Association, began
      a concerted campaign for improved services in the early 1960s. Through
      conferences, seminars, and surveys, they revealed the extent of student distress,
      and by 1965 their efforts were attracting increasing media attention and having a
      direct impact on university student health policies. Their campaign then entered
      a new phase, transformed by the same radicalization that infused the wider
      student movement in the wake of the Berkeley free speech protests. Dissatisfied
      with the institutional response and distrustful of the motives behind the
      services now provided, activists questioned the very meaning of 'mental health'
      in the context of their deeper critique of the university and society. By the end
      of the decade, the student mental health movement had run its course, but it left
      a lasting legacy in the ongoing reform of university health services and in
      attitudes towards student mental health.

PMID- 22145175
TI  - Rats in Alberta: looking at pest-control posters from the 1950s.
AB  - How did the rat-control program, launched by the Government of Alberta in 1950,
      become associated with the identity and heritage of the province? The authors
      answer this question by undertaking close visual analyses of the anti-rat posters
      and pamphlets that were distributed by the government throughout the 1950s. Using
      a visual methodology inspired by semiotics, they argue that the early rat-control
      program ambitiously promoted Alberta as a unified, clean province that was both
      distinct from its prairie neighbours and for the most part populated with
      vigilant, hardworking citizens eager to remove unwanted intruders.

PMID- 22145176
TI  - Help for all parents?: Child-rearing advice in English Canada in the 1960s and
      1970s.
AB  - Changes occurring in Canadian society during the 1960s and 1970s were poorly
      reflected in the child-rearing advice directed to English-Canadian parents.
      Despite the rise in the number of women working outside the home and feminist
      calls for a more equitable division of child care, experts only sometimes
      modified their advice to acknowledge this reality. In addition, the creation of
      the welfare state seemed to encourage child-rearing advisors to ignore class
      disparities. Finally, experts in this period rarely acknowledged any racial
      diversity in the Canadian population, despite an increasingly multicultural
      society. They continued to presume as the norm a white, Anglo-Saxon, middle-class
      family in which mothers remained the primary caregivers.

PMID- 22145177
TI  - The Bruce Report and social welfare leadership in the politics of Toronto's
      "Slums", 1934-1939.
AB  - Slum clearance and rebuilding first became a serious political project in Toronto
      during the 1930s. Following the release of a systematic housing survey known as
      the Bruce Report (1934), a set of actors distinguished by their planning
      authority with respect to social agencies, influence over social work education,
      coordination of social research, and role as spokespersons of religious bodies
      inaugurated a political struggle over state power. While the campaign failed, it
      called forth a reaction from established authorities and reconfigured the local
      political field as it related to low-income housing. This article gives an
      account of these processes by drawing upon correspondence and minutes of meetings
      of city officials and the campaign's organizers, newspaper clippings, and
      published materials.

PMID- 22145178
TI  - The modern Chinese family in light of economic and legal history.
AB  - Most social science theory and the currently powerful Chinese ideology of
      modernizationism assume that, with modern development, family-based peasant farm
      production will disappear, to be replaced by individuated industrial workers and
      the three-generation family by the nuclear family. The actual record of China's
      economic history, however, shows the powerful persistence of the small family
      farm, as well as of the three-generation family down to this day, even as China's
      GDP becomes the second largest in the world. China's legal system, similarly,
      encompasses a vast informal sphere, in which familial principles operate more
      than individualist ones. And, in between the informal-familial and the formal
      individualist, there is an enormous intermediate sphere in which the two
      tendencies are engaged in a continual tug of war. The economic behavior of the
      Chinese family unit reveals great contrasts with what is assumed by conventional
      economics. It has a different attitude toward labor from that of both the
      individual worker and the capitalist firm. It also has a different structural
      composition, and a different attitude toward investment, children's education,
      and marriage. Proper attention to how Chinese modernity differs socially,
      economically, and legally from the modern West points to the need for a different
      kind of social science; it also lends social-economic substance to claims for a
      modern Chinese culture different from the modern West's.

PMID- 22145179
TI  - Text, practice, and life narrative: bridal lamentation and a daughter's filial
      piety in changing rural China.
AB  - This article explores, through the lenses of text, practice, and life narrative,
      how Chinese peasant women as daughters manage patrilocality and carry out-or fail
      to carry out-filial piety toward their parents. Based on field research in a
      locale in southern China conducted since 1992, this article focuses on four
      women's life histories and juxtaposes how these women articulated filial piety as
      daughter-brides in wedding lamentations and how they practiced it after marriage.
      This research illuminates how peasant women perceive daughterly filial piety as a
      complex entailing not only emotional attachment but also peace of mind,
      tolerance, and material support. For these women, concerns about filial piety
      emerge as a focus of their maneuvering and negotiating among the strategic
      possibilities in their lives-their social responsibilities, personal conditions,
      the broader social-political milieu, and above all, the male support that is
      often ignored but indispensable in these women's stories.

PMID- 22145180
TI  - "Abortion will deprive you of happiness!": Soviet reproductive politics in the
      post-Stalin era.
AB  - This article examines Soviet reproductive politics after the Communist regime
      legalized abortion in 1955. The regime's new abortion policy did not result in an
      end to the condemnation of abortion in official discourse. The government instead
      launched an extensive campaign against abortion. Why did authorities bother
      legalizing the procedure if they still disapproved of it so strongly? Using
      archival sources, public health materials, and medical as well as popular
      journals to investigate the antiabortion campaign, this article argues that the
      Soviet government sought to regulate gender and sexuality through medical
      intervention and health "education" rather than prohibition and force in the post
      Stalin era. It also explores how the antiabortion public health campaign produced
      "knowledge" not only about the procedure and its effects, but also about gender
      and sexuality, subjecting both women and men to new pressures and regulatory
      norms.

PMID- 22145181
TI  - Home-grown slaves: women, reproduction, and the abolition of the slave trade,
      Jamaica 1788-1807.
AB  - Once the British transatlantic slave trade came under abolitionists' scrutiny in
      1788, West Indian slaveholders had to consider alternative methods of obtaining
      well-needed laborers. This article examines changes in enslaved women's working
      lives as planters sought to increase birth rates to replenish declining laboring
      populations. By focusing more on variances in work assignment and degrees of
      punishment rather than their absence, this article establishes that enslaved
      women in Jamaica experienced a considerable shift in their work responsibilities
      and their subjection to discipline as slaveholders sought to capitalize on their
      abilities to reproduce. Enslaved women's reproductive capabilities were pivotal
      for slavery and the plantation economy's survival once legal supplies from Africa
      were discontinued.

PMID- 22145182
TI  - Salesclerks, sexual danger, and national identity in Egypt, 1920s-1950s.
AB  - This article investigates change and continuity in anxieties about shopping
      during the first half of the twentieth century in Egypt to argue that department
      stores and their salesclerks became critical sites for enacting and challenging
      new notions of sexuality and citizenship. Retail innovations, such as commission
      pay, display, free entry, and large commercial staffs, became understood as
      sexual and moral problems because department stores blurred the boundaries
      between classes and were public spaces where unrelated men and women could mix.
      These concerns about sexuality in the 1920s were recycled and amplified in the
      late 1940s and early 1950s when salesclerks again came under scrutiny during
      debates over citizenship and ethnicity. I argue that the particular way this
      latter debate was barnacled by the concerns of the 1920s helped to delineate the
      broader society's reaction to the challenges of defining Egyptian nationality.

PMID- 22145183
TI  - Traveling with faith: the creation of women's immigrant aid associations in
      nineteenth and twentieth-century France.
AB  - This article explores the efforts of French Catholic, Protestant, and Jewish
      women to morally, spiritually, and physically protect immigrant and migrant women
      and girls in the late nineteenth and early twentieth centuries. Women of faith
      worried about the dangers posed by the white slave trade, and they feared the
      loss of spiritual consciousness among women living far from their families and
      their places of worship. In response to these concerns, they developed numerous
      faith-based international organizations aimed at protecting vulnerable working
      class immigrants. Upper-class women's work in immigrant aid societies allowed
      them to take on much greater social and religious leadership roles than they had
      in the past. Likewise, the intricate, international networks that these women
      developed contributed to the building of international cooperation throughout
      Europe.

PMID- 22145184
TI  - Healthy vocations: field nursing and the religious overtones of public health.
AB  - This article argues that the Office of Indian Affairs (OIA) field nursing program
      of the 1930s, which continued much of the same assimilation-style health care
      practices begun generations earlier by missionaries and field matrons,
      perpetuated the nineteenth-century link between religion and health care.
      Following in the footsteps of their female predecessors, field nurses targeted
      native women for health education, emphasizing personal hygiene and individual
      responsibility at the expense of socioeconomic causes of illness. Native women
      nonetheless appear to have maintained agency and power in negotiating health and
      health care. Peaking during the era of OIA Commissioner John Collier's Indian New
      Deal, the history of field nursing problematizes this period, particularly with
      regard to women's experiences. The article is significant for its exploration of
      field nursing as a contested site of cultural negotiation, revealing issues of
      power and difference in the lives of American women.

PMID- 22145185
TI  - [Slave work in Costa Rica].

PMID- 22145186
TI  - Medicare program; payment policies under the physician fee schedule, five-year
      review of work relative value units, clinical laboratory fee schedule: signature
      on requisition, and other revisions to part B for CY 2012. Final rule with
      comment period.
AB  - This final rule with comment period addresses changes to the physician fee
      schedule and other Medicare Part B payment policies to ensure that our payment
      systems are updated to reflect changes in medical practice and the relative value
      of services. It also addresses, implements or discusses certain statutory
      provisions including provisions of the Patient Protection and Affordable Care
      Act, as amended by the Health Care and Education Reconciliation Act of 2010
      (collectively known as the Affordable Care Act) and the Medicare Improvements for
      Patients and Providers Act (MIPPA) of 2008. In addition, this final rule with
      comment period discusses payments for Part B drugs; Clinical Laboratory Fee
      Schedule: Signature on Requisition; Physician Quality Reporting System; the
      Electronic Prescribing (eRx) Incentive Program; the Physician Resource-Use
      Feedback Program and the value modifier; productivity adjustment for ambulatory
      surgical center payment system and the ambulance, clinical laboratory, and
      durable medical equipment prosthetics orthotics and supplies (DMEPOS) fee
      schedules; and other Part B related issues.

PMID- 22145187
TI  - RP Summary: Recommended practices for prevention of deep vein thrombosis (DVT).

PMID- 22145188
TI  - Medicare and Medicaid programs: hospital outpatient prospective payment;
      ambulatory surgical center payment; hospital value-based purchasing program;
      physician self-referral; and patient notification requirements in provider
      agreements. Final rule with comment period.
AB  - This final rule with comment period revises the Medicare hospital outpatient
      prospective payment system (OPPS) for CY 2012 to implement applicable statutory
      requirements and changes arising from our continuing experience with this system.
      In this final rule with comment period, we describe the changes to the amounts
      and factors used to determine the payment rates for Medicare hospital outpatient
      services paid under the OPPS. In addition, this final rule with comment period
      updates the revised Medicare ambulatory surgical center (ASC) payment system to
      implement applicable statutory requirements and changes arising from our
      continuing experience with this system. In this final rule with comment period,
      we set forth the relative payment weights and payment amounts for services
      furnished in ASCs, specific HCPCS codes to which these changes apply, and other
      ratesetting information for the CY 2012 ASC payment system. We are revising the
      requirements for the Hospital Outpatient Quality Reporting (OQR) Program, adding
      new requirements for ASC Quality Reporting System, and making additional changes
      to provisions of the Hospital Inpatient Value-Based Purchasing (VBP) Program. We
      also are allowing eligible hospitals and CAHs participating in the Medicare
      Electronic Health Record (EHR) Incentive Program to meet the clinical quality
      measure reporting requirement of the EHR Incentive Program for payment year 2012
      by participating in the 2012 Medicare EHR Incentive Program Electronic Reporting
      Pilot. Finally, we are making changes to the rules governing the whole hospital
      and rural provider exceptions to the physician self-referral prohibition for
      expansion of facility capacity and changes to provider agreement regulations on
      patient notification requirements.

PMID- 22145189
TI  - Implementation of the Methamphetamine Production Prevention Act of 2008. Final
      rule.
AB  - In October 2008, the President signed the Methamphetamine Production Prevention
      Act of 2008 (MPPA), which clarifies the information entry and signature
      requirements for electronic logbook systems permitted for the retail sale of
      scheduled listed chemical products. On March 23, 2010, DEA published a Notice of
      Proposed Rulemaking to implement the provisions of the MPPA and make its
      regulations consistent with the new requirements. This action finalizes without
      change the Notice of Proposed Rulemaking published on March 23, 2010. The Final
      Rule will make it easier for regulated sellers to maintain electronic logbooks by
      allowing greater flexibility as to how information may be captured.

PMID- 22145190
TI  - Intracellular proteolytic activity of the haloalkaliphilic archaeon Natronococcus
      occultus. Effect of starvation.
AB  - Intracellular proteolytic activity was detected in the haloalkaliphilic archaeon
      Natronococcus occultus during the stationary phase of cultures grown in complete
      medium and during carbon and nitrogen starvation. Puromycin prevented the
      occurrence of proteolytic activity in starved cells, suggesting that de novo
      synthesis of proteolytic enzymes might be required for protein degradation during
      starvation. Intracellular proteolytic activity degraded casein and gelatin. It
      had a temperature optimum of 60 degree centigrade in 2 M NaCl and depended on
      high salt concentration (NaCl or KCl) for activity and stability. Gelatin
      zymography of cell extracts from stationary phase or starved cells showed a
      complex pattern of proteolytic bands ranging from ~ 20 to 120 kDa. All these
      proteolytic bands were inhibited by PMSF1) and chymostatin. However, they showed
      differences in stability to temperature and salt concentration.

PMID- 22145191
TI  - Servicemembers' Group Life Insurance Traumatic Injury Protection program-
      genitourinary losses. Interim final rule.
AB  - The Department of Veterans Affairs (VA) is issuing this interim final rule that
      amends the regulations governing the Servicemembers' Group Life Insurance
      Traumatic Injury Protection (TSGLI) program by adding certain genitourinary (GU)
      system losses to the TSGLI Schedule of Losses and defining terms relevant to
      these new losses. This amendment is necessary to make qualifying GU losses a
      basis for paying GU-injured Servicemembers TSGLI benefits. The intended effect is
      to expand the list of losses for which TSGLI payments can be made.

PMID- 22145192
TI  - Preventing catheter-related urinary tract infection: focus on Proteus mirabilis.
AB  - Urinary tract infectious caused by Proteus are uncommon, and account for only 1
      2% of community-acquired infectious. However, it is important that staff are able
      to recognise the features of a Proteus infection. Proteus infections, if
      unrecognised, can become established and cause major health problems. Proteus is
      more common in people who have or have had a urinary catheter. Minimizing the
      incidence and duration of urinary catheterization is an important part of
      preventing infection. Community staff who are alert to the possibility of this
      infection can make a huge difference to their patient's quality of life.

PMID- 22145194
TI  - Assessing appropriateness of coronary intervention.

PMID- 22145193
TI  - A review of electrocardiography in pulmonary embolism: recognizing pulmonary
      embolus masquerading as ST-elevation myocardial infarction.
AB  - A 64-year-old woman with hypertension and diabetes presented with acute shortness
      of breath and left-sides chest discomfort. Electrocardiopgram (ECG) demonstrated
      Q waves, coved ST-segment elevations, and T-wave inversions in leads V1-V4,
      suggesting acute anterior ST-elevation myocardial infarction (STEMI).
      catheterization revealed nonocclusive coronary artery disease with elevated
      pulmonary and right heart pressures, confirmed by echocardiography. Ventilation
      perfusion scan was deemed high probability for pulmonary embolism (PE). Treatment
      for a submassive PE was initiated and ECG changes resolved by discharge. This
      case exemplifies similarities in clinical presentation of PE and acute STEMI. The
      presence of Q waves in anterior leads wih coved ST-elevation after PE has not
      been described previously. We review the differential diagnosis of ST elevation
      and the assorted spectrum of ECG changes seen in PE.

PMID- 22145195
TI  - Nothing endures but change. Perspectives.

PMID- 22145196
TI  - Wesley L. Nyborg, PhD, 1917-2011.

PMID- 22145197
TI  - Strengthening primary care: recent reforms and achievements in Australia,
      England, and the Netherlands.
AB  - Recent reforms in Australia, England, and the Netherlands have sought to enhance
      the quality and accessibility of primary care. Quality improvement strategies
      include postgraduate training programs for family physicians, accreditation of
      general practitioner (GP) practices, and efforts to modify professional behaviors
      for example, through clinical guideline development. Strategies for improving
      access include national performance targets, greater use of practice nurses,
      assured after-hours care, and medical advice telephone lines. All three countries
      have established midlevel primary care organizations both to coordinate primary
      care health services and to serve other functions, such as purchasing and
      population health planning. Better coordination of primary health care services
      is also the objective driving the use of patient enrollment in a single general
      practice. Payment reform is also a key element of English and Australian reforms,
      with both countries having introduced payment-for-quality initiatives. Dutch
      payment reform has stressed financial incentives for better management of chronic
      disease.

PMID- 22145198
TI  - [Racial ideology, social policy, and the liberal state    in Costa Rica].

PMID- 22145199
TI  - [Images in conflict: changes in childhood and the welfare state in Swedish
      society. Reflections on the century of the child].

PMID- 22145200
TI  - [The education of Antillean Indians and    mestizos in the first half of the the
      16th century].

PMID- 22145201
TI  - [Cattle on Hispaniola, 1508-87].

PMID- 22145202
TI  - [Costa Rican identity and cultural diversity:    a possible challenge?].

PMID- 22145203
TI  - [The righteous province of Chiloe:    witchcraft, 18th-20th centuries. Part 1].

PMID- 22145204
TI  - [Mexican merchants confront death, 1765-1800].

PMID- 22145205
TI  - [The origins of slaves in the Americas:    methodological perspectives].

PMID- 22145206
TI  - [The real firing wound of type of skull perforation and head penetration compared
      with the mathematical model of behaviour of FMJ pistol projectile of calibre of
      6.35 mm Browning (25 Auto)].
AB  - Searching for the answer whether the bullet cal. 6.35 mm Browning (25 Auto) could
      entrance the human skull and stay inside without resting the head against the
      solid barrier inside the vehicle, forensic experts in the field of ammunition and
      wound ballistics used mathematical model of the monoogival pistol bullet's
      velocity decrease through the penetration of the several type of human tissue due
      to physical and mechanical properties. The result of the expert's terminal
      ballistics task was the mathematical prediction of wound track length at the
      moment of bullet's stop in the tissue. The results has been compared with the
      cases where the similar weapon system with the resembling energetic output has
      been used.

PMID- 22145207
TI  - [Taxus baccata poisoning].
AB  - Common yew poisoning occurs by per oral application of needles or extracts of
      needles usually. The determination of the cause of death is more difficult in the
      latter case. In our article, we advise of circumstances which could be helpful in
      diagnostic. In addition, we describe the substances contained in yew, their
      effect, importance and toxicological detection.

PMID- 22145208
TI  - [Breath alcohol test--screening or evidence?].
AB  - According to Slovak legislation any individual consuming ethanol may, under
      certain conditions, face substantial legal consequences. It is generally known
      that results of almost any breath alcohol test may be challenged by an
      experienced defense attorney using scientific principles of these tests. Most
      common of these legal attacks on breath alcohol test are presented. Lack of
      attention to this matter from medico-legal societies in Slovak and Czech Republic
      is also pointed out.

PMID- 22145209
TI  - [Therapeutic indicators in pathology--from "bench to bedside"].

PMID- 22145210
TI  - [Pancreatic carcinoma is still a sad chapter in medicine. Interview by J.
      Zamecnik].

PMID- 22145211
TI  - [Predictive diagnosis of breast cancer].
AB  - Detection of selected predictive markers is currently included in the standard
      diagnostic algorithm of breast carcinoma specimens. Despite this fact we are
      facing several unresolved questions and issues. Probably the most frequently
      discussed predictive marker in breast carcinoma is HER-2/neu. The change of
      criteria of positivity in 2007 brought several confusions regarding the selection
      of patients eligible for anti-HER2 treatment. There is a deficiency of knowledge
      in tumors with the discordant phenotype (a discrepancy between the results of
      immunohistochemistry and in situ hybridization). Even in selected HER2 positive
      patients is the anti-HER2 treatment effective in only 30 % of cases. Thus, we
      evidently have to search for new markers which would help to more precisely
      select the optimal treatment for breast cancer patients.

PMID- 22145212
TI  - [Gastrointestinal stromal tumor molecular diagnostics in relation to the
      prediction of a therapeutic response to targeted biological therapy].
AB  - Targeted therapy based on the inhibition of the receptor tyrosine kinases has
      improved the outcome of patients with metastatic, recurrent and/or unresectable
      gastrointestinal stromal tumors (GIST). Activating mutations of KITand PDGFRA
      genes, which code for receptor tyrosine kinases, play an important role in the
      malignant transformation of stromal cells in the gastrointestinal tract. The
      response to targeted therapy is associated with the presence and type of
      mutations. Molecular identification of the primary mutational status became an
      important tool in predicting the response to therapy (sensibility/resistance).
      The identification of secondary mutations occurring in patients treated with
      targeted therapy may explain the cause of acquired, secondary resistance of GIST.
      In these cases, mutational analysis represents a tool to explain failure of the
      therapy and provides a rationale for alternative therapeutic strategies.

PMID- 22145213
TI  - [Molecular predictive markers of EGFR-targeted therapy in metastatic colorectal
      cancer].
AB  - The monoclonal antibodies panitumumab and cetuximab that target the epidermal
      growth factor receptor are effective in approximately 10% and 20% of EGFR
      expressing, chemotherapy resistant metastatic colorectal cancer patients in
      monotherapy and in combination with chemotherapy, respectively. The evidence that
      EGFR expression by immunohistochemistry does not predict clinical outcome in EGFR
      targeted treatment has led to an intensive search for additional predicitive
      biomarkers. Oncogenic activation of signalling pathways downstream of the EGFR,
      such as mutation of KRAS, BRAF, or PIK3CA oncogenes, or inactivation of the PTEN
      tumor supressor gene is central to the progression of colorectal cancer. Tumor
      KRAS mutation, which may be present in 35%-45% of patients with colorectal
      cancer, is now recognized as an important predictive marker of resistance to
      cetuximab or panitumumab treatment and is also widely used in clinical practice.
      Among tumors carrying wild-type KRAS, mutations of BRAF or PIK3CA or loss of PTEN
      expression may be associated with resistance to the anti-EGFR monoclonal antibody
      treatment. On the other hand, EGFR ligands overexpression detected in tumor
      tissue is a promising positive predictive marker. There are also some initial
      observations that gene expression profiling could also contribute to clinical
      decision-making about the cetuximab and panitumumab treatments. These
      observations require further validation in prospective clinical trials before
      incorporation into clinical practice.

PMID- 22145214
TI  - [Predictive diagnosis of HER2 in gastric adenocarcinoma].
AB  - Trastuzumab is a monoclonal antibody directed against the human epidermal growth
      factor receptor 2 (HER2). This receptor is overexpressed in approximately 20% of
      gastric adenocarcinomas. The overexpression is associated with a worse prognosis,
      but on the other hand, patients with HER2-positive cancers were shown to benefit
      from the addition of trastuzumab to standard chemotherapy. To begin the targeted
      therapy with trastuzumab, HER2 testing is now mandatory with immunohistochemistry
      being the primary test followed by in situ hybridization analysis of HER2
      amplification in cases with equivocal immunopositivity (score 2+). The
      immunohistochemical HER2 scoring system has been modified to include incomplete
      basolateral and lateral membrane staining, and to differentiate between surgical
      and endoscopical samples of the tumor. Benefit from trastuzumab treatment can be
      expected in tumors showing an immunohistochemical score 3+, and in cases with
      score 2+ and a positive finding of HER2 amplification. Clinical trials with
      further monoclonal antibodies and receptor tyrosine kinase inhibitors are
      recently ongoing to broaden the spectrum of possibilities of a multitargeted
      approach to the treatment of gastric cancer.

PMID- 22145215
TI  - [Targeted therapy of melanoma: fact or fiction?].
AB  - Advanced malignant melanoma is incurable by the current means of therapy.
      Traditional morphological classification (nodular melanoma, lentigo maligna
      melanoma, nevoid melanoma etc.) does not have any significant prognostic or
      predictive impact. Recent advances in molecular pathogenesis and the availability
      of targeted therapies have produced several positive results. In the near future,
      the main challenge for pathologists, geneticists and oncologists will be the
      identification of accurate therapeutic targets, as well as mechanisms of
      resistance, in melanoma in the particular patient in care.

PMID- 22145216
TI  - [News in the classification of pulmonary adenocarcinomas and potential prognostic
      and predictive factors in non-small lung cancer].
AB  - Lung cancers are still divided into two major subgroups: small-cell and non-small
      cell lung cancer (NSCLC) irrespective of biological heterogeneity of NSCLC. It is
      a key task of the pathologist to provide an accurate classification of tumorous
      lesions to avoid the term NSCLC and to use it only in the vast minority of cases.
      Moreover, the most recent reclassification of pulmonary adenocarcinomas should be
      reflected in the standard biopsy protocol reporting. There is also an
      increasingly urgent need to provide high quality material for testing of the
      genetic characteristics of NSCLC, especially the presence and functional status
      of the EGFR receptor (epidermal growth factor receptor), as well as other
      potential prognostic markers. The requirement for the quality and swiftness of
      diagnosis puts major emphasis on the close multidisciplinary collaboration with
      the central role of a specialized pathologist, who coordinates the differential
      diagnostic procedure. This in turn implies the necessity of accounting for the
      increasing financial burden of diagnostic departments.

PMID- 22145217
TI  - [Clinical registers as a necessary support for personalized medicine].
AB  - The article is an overview of major trends in the development of diagnostic and
      clinical registries which constitute a significant component of the informational
      background of personalized medicine. The rapid development of diagnostic methods
      has allowed data analysis to enter into the decisions about diagnosis and
      treatment of many diseases. However, practical application of the analyses still
      has serious limits related to the availability of complex, quality data. The
      basic trends of research in this field are the increasing standardization of
      content and structure of clinical databases and their association with clinical
      patient's records on an individual basis and ensuring the development of modern
      analytical tools.

PMID- 22145218
TI  - [What is your diagnosis? Metastatic sarcoma with interdigitating dendritic cells
      in lymph nodes].

PMID- 22145219
TI  - [Giant cutaneous basal cell carcinoma of the head with intracranial propagation-
      a case report].
AB  - Basal cell carcinoma (BCC) of the skin is generally characterised by a favourable
      clinical outcome. The slow and mostly local character of growth helps in its
      early recognition, thus the vast majority of cases are diagnosed in the early
      phase of disease. However, in cases of long-term neglect of clinical symptoms,
      certain cancers may reach huge proportions and may significantly destroy
      surrounding tissue. BCCs larger than 5 cm are called giant BCCs. The authors of
      the article present a case report of woman suffering from a giant BCC of the head
      with a history of 15 years of lasting growth, during which she had refused a
      medical examination. Finally, she was forced to go into hospital due to episodes
      of unconsciousness and convulsions. Clinical investigations revealed a huge
      ulcerating tumour in the fronto-parietal region infiltrating the skull and
      penetrating into the cranial cavity with compression of the brain. A surgical
      extirpation of the tumor-affected soft tissue and the calva was performed with
      plastic reconstruction of dura mater and skin. Microscopic examination of biopsy
      specimens confirmed a diagnosis of mixed BCC with nodular, infiltrative and
      metatypical features, which had completely infiltrated calva and dura mater. It
      was not possible to surgically remove a part of the tumour-affected bones of the
      left orbita, thus the patient is going to undergo local radiotherapy. This case
      report emphasizes the fact that BCC, in spite of its usually "benign" biological
      behaviour, should never be underestimated because it may progress to the advanced
      stage of the disease, for which treatment is much more difficult with a larger
      negative impact and a significantly worse prognosis for the patient.

PMID- 22145220
TI  - [Acatholytic variant of squamous carcinoma of the breast. A case report and
      review of literature].
AB  - The acantholytic variant of squamous carcinoma (ASC) represents a rare type of
      metaplastic breast carcinoma with typical occurrence of pseudoglandular and
      pseudovascular structures, arising as a result of cohesion loss between the
      neoplastic cells. Up to the present, there have been only 10 cases of mammary ASC
      described in the English written literature. The authors present a case of a 57
      year-old woman with a large (6 x 7 cm) suspicious lump on ultrasonography in her
      right breast treated by mastectomy with an ipsilateral axillary lymph node
      dissection due to histologically verified ASC. Additional postoperative staging
      computer tomography revealed metastatic foci in the left lungs, thus calling for
      adjuvant chemotherapy for the patient. Six months after setting the diagnosis,
      the patient is alive with a partial therapeutic response. In the differential
      diagnosis of ASC it is important to exclude angiosarcoma, phyllodes tumor and
      metastatic sarcomas to the breast. The useful tools for differentiation between
      the above-mentioned entities are extensive bioptic examination and detailed
      immunohistochemical staining, enabling the pathologist to exclude the endothelial
      lineage (using CD31 and CD34) and to verify the epithelial origin through the
      detection of cytokeratins (spectra of high-molecular weight cytokeratins).
      Furthermore, the ASC shows positive immunohistochemical staining for markers of
      the myoepithelial differentiation, e.g. cytokeratin 14, CD10 and p63, suggesting
      an immature cell population with basaloid features. In conclusion, as ASC is an
      aggressive subtype of the breast carcinoma with a poor prognosis, the correct
      diagnosis set by the pathologist is of great importance on the therapeutic
      management in affected patients.

PMID- 22145221
TI  - Intrapericardial teratoma as a cause of fetal death--a case report.
AB  - Intrapericardial teratoma is a rare congenital tumor that without treatment leads
      to cardiac failure in either the prenatal or postnatal period. Early diagnosis
      and recent surgical advances can, in some cases, delay development of
      intrauterine symptoms and allow final treatment through a tumor resection.
      However, a large number of intrapericardial tumors go undetected during prenatal
      diagnostics, until they are found as a cause of intrauterine death or postnatal
      cardiorespiratory insufficiency, as in our case report. An abortion was induced
      in the 23rd gestational week because there was no cardiac activity detected
      during a routine ultrasound scan in a 35-year old woman. The tumor was found
      during the postmortem of the fetus.

PMID- 22145222
TI  - [Carney complex].
AB  - Carney complex is a clinically and genetically heterogeneous disease, with at
      least two genetic loci including the PRKAR1A gene located on chromosome 17 and
      the CNC2 locus mapped to chromosome 2. Clinically this syndrome is characterized
      by multiple myxomas occurring in different anatomic sites, mucocutaneous
      pigmentary lesions, and a variety of non-endocrine and endocrine tumors, often
      causing endocrine abnormalities, involving various organs. Knowledge of
      morphological findings in CNC patients with their typical locations is necessary
      to raise suspicion of this syndrome by pathologists. Confirmation of the
      diagnosis allows regular clinical check-ups and early treatment of these
      patients.

PMID- 22145223
TI  - [Primary sclerosing cholangitis].

PMID- 22145224
TI  - [Investigation of antiviral activity of adamantan boron derivaties on pandemic
      influenza virus models].
AB  - Comparative investigation of the virus-inhibiting activity of some boron
      containing compounds showed that products BG 12 and BG 4 had the highest
      inhibitory effect on pandemic viruses. The minimum inhibitory concentration (MIC)
      of the products was 0.1 mcg/ml. The use of liposomes loaded with BG 12 molecules
      in the optimal concentration (0.1 mcg/ml) resulted in inhibition of the avian
      plague virus growth in the MDCK cells. Possible design of efficient drugs for
      antiviral protection based on the complexes liposomes--boron-containing compounds
      is discussed.

PMID- 22145225
TI  - [Experimental study of Grippferon antiviral activity against Mexican pandemic
      influenza virus A/H1N1/2009 in vitro].
AB  - Analysis of the efficacy of Grippferon vs. the reference drugs Realdiron and
      Reaferon-EC against the influenza virus A(H1N1)/2009 in susceptible static cell
      cultures showed that in the concentrations tested it was efficient in inhibition
      of the virus cytopathic activity and generation of specific hemagglutinin.

PMID- 22145226
TI  - [Population pattern of pneumococci with lower susceptibility to penicillin and
      prospects of antipneumococcal vaccination to control antibiotic resistance
      distribution].
AB  - Large-scale antipneumococcal vaccination is followed by changes in the serotype
      composition and level of antibiotic resistance in pneumococci. The aim of the
      study was to evaluate the serotype composition and population pattern of
      pneumococci with lower susceptibility to penicillin before large-scale
      antipneumococcal vaccination. Among 260 Streptococcus pneumoniae strains isolated
      in the Russian Federation within 2003-2007, serotypes 23F (37.2%) and 19F (13.9%)
      were the most frequent ones. 19.3% of the isolates belonged to serogroup 6, 3.6%
      of the isolates each belonged to serotype 3 and serogroup 18, 4.9% of the
      isolates belonged to serotype 14 and 2.2% of the isolates belonged to serotype
      19A. 66.8% of the isolates belonged to serotypes of the 7-valent conjugated
      pneumococcal vaccine, 67.3 and 82.1% of the isolates belonged to the 10- and 13
      valent conjugated pneumococcal vaccines respectively. The isolates with lower
      susceptibility to penicillin were characterized by significant clonality and
      56.9% of them belonged to 4 global clonal complexes (CC81, CC156, CC320 and
      CC315). Inclusion of the conjugated antipneumococcal vaccine to the National
      Vaccination Time-Table of the Russian Federation could promote lower levels of
      antibiotic resistance in pneumococci.

PMID- 22145227
TI  - [Analysis of the spectrum of bacterial pathogens isolated from patients with
      complicated skin and soft tissue infections presumably due to grampositive or
      mixed flora in the countries of the Central and East Europe].
AB  - The data on the microbiological investigation of clinical materials from patients
      with complicated skin and soft tissue infections in 6 European countries were
      analysed. The analysis of the bacterial pathogens spectrum provided the microbial
      view and efficient use of novel antimicrobials in clinical trials.

PMID- 22145228
TI  - [Antibiotic susceptibility of isolates from blood of patients in intensive care
      units of emergency medical service].
AB  - The microbiological tests of 769 blood samples from 220 patients, treated in 4
      intensive care units of the N.V. Sklifosovsky Research Institute for Emergency
      Medical Service within a period from January 2009 to June 2010, were analysed.
      Etiologically significant microorganisms were detected in 323 samples (42%). 253
      isolates were used in the analysis. Grampositive and gramnegative pathogens were
      detected in 47 and 42% of the cases respectively. Candida and anaerobic organisms
      were isolated in 8 and 3% of the cases respectively. Staphylococcus aureus and
      enterococci were isolated in 24 and 15% of the cases respectively. Nonfermenting
      gramnegative bacteria and enterobacteria were revealed in 25 and 17% of the cases
      respectively. Differences in the spectrum of the sepsis pathogens depending on
      the patients contingent were shown. The maximum summary susceptibility of the
      grampositive cocci was observed with respect to vancomycin and linezolid and that
      of the gramnegative bacteria was stated with respect to imipenem and meropenem.

PMID- 22145229
TI  - [Antibiotic resistance dynamics and isolation rate of staphylococci and
      enterococci from patients of reconstructive surgery units].
AB  - The dynamics of isolation of staphylococci and enterococci from clinical material
      of patients and their antibiotic susceptibility within a 5-year period (2005
      2009) was analysed. 5990 isolates were tested: 1250 isolates of Staphylococcus
      aureus, 3268 isolates of S. epidermidis, 1005 isolates of Enterococcus faecalis
      and 467 isolates of E. faecium. Grampositive infections were shown to be
      prevailing within the last 2-3 years, the nosocomial epidermal staphylococci more
      and more replacing S. aureus (the ratio of S. epidermidis and S. aureus in 2009
      was 3.3). The isolation rate of E. faecalis significantly increased (by 3.5
      times) and the ratio of E. faecalis and E. faecium in 2009 was 4.3. The
      microflora composition with respect to the isolation source was analysed and its
      clinical significance was estimated. The study of the antibiotic susceptibility
      showed that oxacillin had its own specific niche, while antibiotics active
      against resistant grampositive cocci, such as rifampicin, fusidic acid,
      fluoroquinolones (moxifloxacin), cefoxitin, as well as amoxicillin/clavulane in
      infections due to E. faecalis, might be considered as the drugs of choice. In the
      treatment of nosocomial infections, when the etiological role of MRSA or VRE is
      suspected or confirmed, the complex therapy should obligatory include the most
      active antibiotics (vancomycin or linezolid among them).

PMID- 22145230
TI  - [Is antiviral therapy in gastroduodenal pathology necessary?].
AB  - Mucous membrane of the gastroduodenal region of 104 patients with different
      pathologies (gastritis and erosive ulcerative alterations) was investigated by
      polymerase chain reaction (PCR). Examination of the biopsy material revealed
      frequent occurrence of pathogenic strains of Helicobacter pylori (up to 80%) and
      Herpesviridae (EBV, HHV 6, HHV 7, HHV 8) in various combinations. In such cases
      it is necessary to use adequate antibacterial and antiviral therapy with
      individual choice of immunomodulators.

PMID- 22145231
TI  - [Clinicoimmunological monitoring of therapy in patients with associated forms of
      yersiniosis].
AB  - Characteristics of the clinical process and immunological profile in children
      with yersiniosis as a monoinfection or in association with acute intenstinal
      infections and virus hepatitis A are presented. The efficacy of the immunotropic
      therapy with cycloferon, an interferon inductor, and recombinant interferon in
      the patients with the viral and bacterial association of the disease (yersiniosis
      + hepatitis A) and initial disbalance of the serum cytokines was estimated.
      Dependence of the interferon clinicolaboratory efficacy on the initial levels of
      serum y-interferon, IL2 and IIA, promoting shorter terms of hyperthermia,
      diarrhea syndrome and cytolysis syndrome was shown. It allowed to optimize the
      scheme of the pathogenetic therapy of Yersinia mixed infection.

PMID- 22145232
TI  - [Manifestations of immune deficiency in children with perinatal HIV infection in
      the treatment dynamics].
AB  - Clinical and immunological parameters in the children with perinatal HIV
      infection were investigated in the dynamics of the long-term prospective
      observation. It was revealed, that all the HIV infected children had clinical
      signs of immunodeficiency and laboratory signs of combined damage of the immune
      system. The complex of therapeutic measures, including antiretroviral therapy,
      prevention of opportunistic and acute respiratory infections, rational
      immunotherapy to stimulate production of endogenous interferon and normalization
      of the balance of cytokines significantly reduced the frequency of the clinical
      manifestations of the infectious syndrome and improved the patients resistance to
      infections.

PMID- 22145233
TI  - [Optimization of treatment of patients with chronic cardiac insufficiency of the
      ischemic genesis and hobnail liver].
AB  - Clinical efficacy of combined therapy including the use of rifaximin and L
      ornithin-l-aspartate, as well as the dynamics of the biochemical indices, the
      manifestation levels of portal-systemic-encephalopathy and intestinal
      microbiocynosis were investigated in patients with chronic cardiac insufficiency
      of ischemic genesis and hobnail liver. The combined therapy resulted in
      improvement of the patients clinical state, lower levels of the portal-systemic
      encephalopathy manifectation by decreasing hyperammonium, normalization of the
      large intestine microflora, and blood serum biochemical parameters.

PMID- 22145234
TI  - [What is ailing the nails? Yellow nail syndrome].

PMID- 22145235
TI  - [Cosmetic therapy of hirsutism. With laser and electric current against a hairy
      problem].

PMID- 22145236
TI  - [Experiences from general practice. 30 to 50% of patients have a good outcome
      with the laser (interview by Dr. Beate Schumacher)].

PMID- 22145237
TI  - [ Hypothermia after resuscitation. Better prognosis for cool patients].

PMID- 22145238
TI  - [Recurrent thrombophlebitis in a 70-year-old patient. What can be done as
      prophylactically?].

PMID- 22145239
TI  - [Pain, aggression, food refusal. Can you recognize the faces of depression in the
      elderly?].

PMID- 22145240
TI  - [A "considerate" elderly lady].

PMID- 22145241
TI  - [Naturopathy consultation. Dry cough].

PMID- 22145242
TI  - ["Healthy" people can bear sickness better].

PMID- 22145243
TI  - [Opportunities and limits of influence in food habits].

PMID- 22145244
TI  - [Running against dementia?].

PMID- 22145245
TI  - [Emergency checklists: rib fracture].

PMID- 22145246
TI  - [Primary cytomegalovirus infection in patients without immunodeficiency].

PMID- 22145247
TI  - [The role of triple-drug, fixed-dose combinations for the treatment of
      hypertension].

PMID- 22145248
TI  - [Vertigo in elderly patients. Early therapy chronification].

PMID- 22145249
TI  - Subcutaneous allergen specific immunotherapy: best clinical practice as
      cornerstone for future development.
AB  - Allergen subcutaneous immunotherapy is a long lasting treatment which can modify
      the natural history of allergic respiratory diseases. Recommended administration
      is required for a minimum of three years. During this long term therapy the daily
      management is based on two crucial points, discussed in this review, such as the
      prevention and the treatment of side effects and the improvement and follow-up of
      patient adherence. This review specifically focuses on subcutaneous
      immunotherapy.

PMID- 22145250
TI  - Mite allergens: an overview.
AB  - Mite allergens from the Pyroglyphidae family are the most frequent and potent
      sources of perennial asthma and rhinitis. Since 1988 molecular knowledge has
      considerably increased and structures and functions have been determined for most
      of them. Of the 22 denominated allergens, Der p 1 and Der p 2 are major allergens
      recognized by more than 80% of lgE from Dpt allergic patients in Europe. Der p 4,
      Der p 5 and Der p 7 appeared to be intermediate allergens. The binding of IgE to
      groups 3, 6, 8, 9, 10 and 20 is constantly low. Most of the allergens can be
      identified by amino-acid sequences and the tertiary structure of the major
      allergens has been solved. Most Dpt mite allergens are proteolytic enzymes: Der p
      1 for instance is a cysteine protease. Der p 2 has structural homology with MD-2,
      a co-receptor of the Toll-like receptor (TLR4) whose ligand is LPS. Knowledge of
      the mite allergens structure has allowed a better interpretation of cross
      reactions between allergens from the same family or from more distant families.
      From a practical point of view molecular epidemiology has allowed a better choice
      of allergen molecules useful for diagnosis. Finally, new concepts of
      immunotherapy based on genetically engineered hypoallergenic variants of major
      allergens, used alone or in combination, can be considered.

PMID- 22145251
TI  - Efficacy of over-the-counter immunostimulants in the prevention of paediatric
      recurrent acute respiratory tract infections. Criticisms and pitfalls of
      available metanalyses.
AB  - Preschool children frequently suffer from acute respiratory tract infections
      (ARTI). Immunostimulants (ISs) are often administered to reduce their impact.
      This study aimed to establish the efficacy of ISs in the prevention of pediatric
      ARTI through the analysis of systematic reviews (SRs). We explored Medline
      database in October 2010 limiting our search to SRs, that included studies on the
      effectiveness of ISs in the prevention of pediatric ARTI. Six SRs with meta
      analysis (MA) were found. The studies included showed a low methodological
      quality and a high statistical heterogeneity. All papers published on journals
      with impact factor > 1 and a Jadad score > 3 reviewed the efficacy of OM-85. The
      number needed to treat (NNT) was between 2 and 11, depending on the setting.
      CONCLUSIONS: Pediatric ARTI are a social and health care problem. When they
      impair the quality of life of the family a course of OM-85 might be warranted.
      Although scientific knowledge of clinicians may be improved by SRs, MA and
      aggregation of results may not always be the best way to accomplish this.

PMID- 22145253
TI  - Ethics in clinical studies, with special reference to obstetric practice.

PMID- 22145252
TI  - Improvement of shrimp allergy after sublingual immunotherapy for house dust
      mites: a case report.
AB  - The appropriateness of house dust mite specific immunotherapy in patients
      allergic to shrimps still remains unclear We present a clinical case as an
      immunological model for the strong sensitization to tropomyosin with symptoms of
      anaphylaxis due to shrimps and coexisting asthma due to house dust mite. The
      improvement in respiratory symptoms for house dust mite and in the food challenge
      for shrimps during mite immunotherapy with a known and high dosage of tropomyosin
      suggests the hypothesis that efficacy of mite immunotherapy in food allergy to
      tropomyosin may be dose dependent.

PMID- 22145254
TI  - Choice of airway devices in children.

PMID- 22145255
TI  - Dexamethasone in preventing post-dural puncture headache: a randomized, double
      blind, placebo-controlled trial.
AB  - Spinal anesthesia is major complication is Post-Dural Puncture Headache (PDPH)
      which is an intense and debilitating event. We decided to assess if intravenous
      administration of dexamethasone can decrease the incidence and/or intensity of
      this kind of headache. For this purpose 178 patients, who were supposed to
      undergo lower extremity orthopedic surgery, were enrolled in the study . Before
      spinal anesthesia was initiated, the first group (DXM-group) received 2 mL
      intravenous (i.v) dexamethasone whereas the second group (PCB-group) received 2
      mL i.v. normal saline. After termination of surgery, a 7 days follow-up started
      to observe the possible occurrence and intensity of PDPH. There was no
      statistically significant difference between DMX and PCB groups regarding the
      incidence of PDPH. However, the intensity of headache differed between the two
      groups being less severe if IV dexamethasone had been given prophylactically.
      Dexamethasone can be used to decrease the severity of PDPH in patients who
      receive spinal anesthesia.

PMID- 22145256
TI  - Coasting: worth the effort?
AB  - A new anesthesia machine incorporates a "coasting mode", but the extent to which
      a coasting technique can maintain anesthesia at the end of a procedure under
      optimal conditions (closed circuit anesthesia) remains unknown. Sixty-nine
      patients undergoing peripheral or abdominal surgery were assigned to 1 of 9
      groups, depending on when desflurane coasting (in O2/air) was started (after 4,
      9, 16, 25, 36, 49, 64, 81, or 100 min). The end-expired desflurane concentration
      was maintained at 4.5% in O2/air prior to coasting with a conventional anesthesia
      machine. After initiating coasting (using a closed-circuit technique), we
      examined when the end-expired desflurane concentration reached 70, 60, 50, and
      40% of its value during maintenance (= 30, 40, 50 and 60% decrement times,
      respectively). Decrement times increased with increasing duration of anesthesia,
      and varied widely. After 64 min of maintenance anesthesia, the end-expired
      desflurane concentration remained at or above 70, 60, 50, and 40% of its
      maintenance value during 10.3 +/- 2.3, 16.0 +/- 3.5, 25.0 +/- 5.9, and 45.4 +/-
      19.3 min, respectively (average +/- standard deviation). Coasting can briefly
      maintain anesthesia towards the end of a procedure. While savings with an
      automated coasting mode are likely to be modest per patient, they may become
      substantial when multiplied by the number of procedures per day per operating
      room with no increase in the clinical workload of the anesthesia provider.

PMID- 22145257
TI  - Ultrasound as guidance for a combined bilateral supraclavicular and caudal block,
      in order to reduce the total anaesthetic dose in a two year old child after a
      pneumococcal sepsis.
AB  - We present a case of the combination of a bilateral supraclavicular block and a
      caudal block in a two year old boy who needed amputations of four extremities
      after a pneumococcal sepsis. With the use of ultrasound guidance, reduction of
      local anaesthetic dose could be obtained in order not to reach the toxic dose of
      the local anaesthetic. Amputations of four extremities is not common practice. A
      good postoperative pain management is more than a challenge.

PMID- 22145258
TI  - Lipomatous hypertrophy of the interatrial septum: the typical echographic aspect
      is worth being known.
AB  - A 65-year-old man was scheduled for an on-pump coronary artery bypass graft
      procedure because of a three-vessels coronary artery disease. A right atrial mass
      appended to the interatrial septum was discovered during intraoperative
      transoesophageal echocardiography. Therefore, the right atrium was opened. Gross
      examination revealed a fatty lesion of the interatrial septum. A biopsy was
      performed before the atrium was closed. A histological diagnosis of lipomatous
      hypertrophy of the interatrial septum was made. Lipomatous hypertrophy of the
      interatrial septum is a mass of adipocytes infiltrating the interatrial septum.
      The aspect of "dumbbell" produced by the sparing of the Fossa Ovalis is typical.
      The lesion is benign and remains asymptomatic most of the time although it can be
      responsible for cardiac arrhythmias or circulatory obstruction. The typical
      echographic aspect should be known to avoid unnecessary surgical resection.

PMID- 22145259
TI  - Linking sleep and general anesthesia mechanisms: this is no walkover.
AB  - This review aims at defining the link between physiological sleep and general
      anesthesia. Despite common behavioral and electrophysiological characteristics
      between both states, current literature suggests that the transition process
      between waking and sleep or anesthesia-induced alteration of consciousness is not
      driven by the same sequence of events. On the one hand, sleep originates in sub
      cortical structures with subsequent repercussions on thalamo-cortical
      interactions and cortical activity. On the other hand, anesthesia seems to
      primarily affect the cortex with subsequent repercussions on the activity of sub
      cortical networks. This discrepancy has yet to be confirmed by further functional
      brain imaging and electrophysiological experiments. The relationship between the
      observed functional modifications of brain activity during anesthesia and the
      known biochemical targets of hypnotic anesthetic agents also remains to be
      determined.

PMID- 22145260
TI  - A difficult balancing act.

PMID- 22145261
TI  - Growing up & looking for the right IT to support their evolution.

PMID- 22145262
TI  - Seven ways to streamline radiology.

PMID- 22145263
TI  - Keeping an eye on business associates.

PMID- 22145265
TI  - Accidental records keeper. Interview by Elizabeth Gardner.

PMID- 22145264
TI  - Radiology folds into meaningful use mix.

PMID- 22145266
TI  - Metformin and lactic acidosis.

PMID- 22145267
TI  - Circulating tumour cells and circulating endothelial cells as biomarkers in
      oncology.
AB  - Circulating tumour cells (CTC) and circulating endothelial cells (CEC) are
      considered promising biomarkers for tumour aggressiveness and vascular damage.
      Their number in the blood of cancer patients has already demonstrated to be of
      prognostic and predictive value in several studies. In addition, the molecular
      characterization of these cells may provide novel insight in the growth and
      dissemination of cancer, and help the development of new anti-neoplastic drugs.
      Therefore, many attempts have been made to reliably detect these extremely rare
      cells in the blood. In this review, we address the detection, applicability and
      results from clinical trials for both CTC and CEC.

PMID- 22145268
TI  - Nephrotoxicity of anticancer drugs--an underestimated problem?
AB  - Nephrotoxicity is an inherent adverse effect of certain anticancer drugs and may
      result in a variety of functional consequences that include any combination of
      glomerular or tubular dysfunction, hypertension and disturbance of the renal
      endocrine function. The nephrotoxic potential of most anticancer agents
      dramatically increases in the presence of borderline or overt pre-existing
      chronic kidney disease and measurement of renal function is therefore of utmost
      importance in the cancer patient before any treatment is initiated. This review
      summarizes some clinical nephrotoxic side effects of a selection of the most
      frequently used anticancer drugs. The drugs discussed are cisplatin,
      methotrexate, ifosfamide, citumixab and panitumumab, mitocin C and gemcitabine
      and antiangiogenesis drugs.

PMID- 22145269
TI  - Recommended indications for the administration of polyclonal immunoglobulin
      preparations.
AB  - The following recommendations, which aim at standardising and rationalising the
      clinical indications for administering polyclonal immunoglobulins in Belgium,
      were drawn up by a working group of the Superior Health Council. To this end, the
      Superior Health Council organised an expert meeting devoted to"Guidelines for the
      use of immunoglobulins". The experts discussed the indications for immunoglobulin
      use, the'ideal'immunoglobulin preparation, its mechanisms of action, the
      practical issues involved in administering immunoglobulins and their potential
      side effects. The recommendations formulated by the experts were validated by the
      Superior Health Council working group with the purpose of harmonising
      immunoglobulin use in Belgium

PMID- 22145270
TI  - The use of acetyl cholinesterase inhibitors and memantine in nursing home
      residents.
AB  - AIM: Although a high proportion of elderly nursing home residents suffer from
      Alzheimer's disease (AD), data from the literature indicate that they are only
      rarely treated with Acetyl Cholinesterase Inhibitors (ChEls) or memantine. The
      aim of this study was to describe the use of ChEls or memantine by elderly
      residents in nursing homes, suffering from AD and to document who might qualify
      for pharmacological treatment according to the Belgian reimbursement rules.
      METHOD: Descriptive data was collected from 11 nursing homes through a
      standardized questionnaire consisting of a general section for nurses and a
      specific medical section for general practitioners (GP). All residents (N = 1032)
      from these institutions were eligible for inclusion in the study; 718 (69.6%)
      questionnaires were completed by the nurses of which 533 (51.6%) were also
      completed by the GP's. RESULTS: AD was diagnosed in 29.4% (n = 211) of the
      residents of whom 56.4% (n = 119) did not receive an anti-AD treatment, although
      nearly all of these patients fulfilled the Belgian requirements for reimbursement
      of ChEls or memantine. The mental status of the residents was often incompletely
      documented, but it can be estimated that at least an additional 30.1% (n = 216)
      of all screened residents might possibly qualify for reimbursement of ChEls or
      memantine. CONCLUSIONS: Less than half of the AD patients in nursing homes
      receive ChEls or memantine and approximately one third of the residents could
      possibly qualify for reimbursement. Many residents with cognitive deficits remain
      undetected and undiagnosed and consequently do not receive appropriate treatment.

PMID- 22145271
TI  - Better drug knowledge with fewer drugs, both in the young and the old.
AB  - Little is known about drug knowledge of patients, which is relevant for both the
      compliance and quality of pharmacotherapy. Drug knowledge was quantified in 160
      patients in the outpatient clinics of the departments of Internal and Geriatric
      Medicine. Medication knowledge was generally poor, especially among older
      patients. Better knowledge was associated with the use of fewer drugs. Caregivers
      of dementia patients performed as well as younger patients, indicating that older
      people can perform well, if well-instructed.

PMID- 22145272
TI  - Lenalidomide in relapsed refractory myeloma patients: impact of previous response
      to bortezomib and thalidomide on treatment efficacy. Results of a medical need
      program in Belgium.
AB  - The prognosis of multiple myeloma patients has significantly improved since the
      introduction of the novel agents thalidomide, bortezomib and lenalidomide. We
      report the data of a medical need programme with lenalidomide plus dexamethasone,
      conducted in Belgium between August 2007 and March 2008, and including 98
      relapsed refractory multiple myeloma patients. In addition to chemotherapy and
      steroids, all patients had received prior treatment with bortezomib, and 84% of
      them had been exposed to thalidomide. In 52 patients response data could be
      retrieved by post-hoc analysis. A partial remission or better was achieved in 52%
      (49% partial and 3% complete response) of patients, despite a median of 5
      previous anti-myeloma treatment lines. Responses were rapid while the majority of
      patients received lenalidomide with once weekly (also called low-dose)
      dexamethasone. Treatment with lenalidomide plus dexamethasone did prolong overall
      survival by nearly half a year in this population with end-stage myeloma. Overall
      response and quality of response were independent of previous response to
      thalidomide and bortezomib, although the time to progression tended to be shorter
      in thalidomide- and bortezomib-refractory patients. It can be concluded that
      lenalidomide plus dexamethasone is an effective and safe treatment regimen in
      highly refractory multiple myeloma patients, and that these responses are
      irrespective of previous exposure or sensitivity to thalidomide and bortezomib.

PMID- 22145273
TI  - Why a chest physician should be interested in abdominal pain.
AB  - A 37-year-old woman presented at casualty with a 1-day history of progressive
      spontaneous left iliac fossa pain. She was having her menstruations for 4 days.
      She had no respiratory symptoms. Her medical history consisted of laparoscopic
      surgery for endometriosis and ovarian cysts. A very small right basal
      pneumothorax with visualisation of a hypervascular nodular lesion on the right
      diaphragm was incidentally noticed on the right diaphragm. We suspected here a
      catamenial pneumothorax. During video-assisted thoracoscopy the surgeon observed
      in the centrum tendineum of the diaphragm a small and a large perforation with
      partial intrathoracic herniation of the liver, but without visible diaphragmatic
      or pleural endometriosis. The surgeons converted to a small anterior thoracotomy
      in order to reinforce the large perforation with interrupted non-absorbable
      sutures and plication of the smaller perforation, and finally performed a
      mechanical pleural abrasion with a surgical pad.

PMID- 22145274
TI  - An unexpected pulmonary arterial aneurysm in a COPD patient.
AB  - We present a case of an idiopathic pulmonary artery aneurysm in an asymptomatic
      patient who was treated for an irrelevant medical condition. Pulmonary artery
      aneurysms (PAA) are quite rare and can either be congenital or acquired.
      Congenital aneurysms are usually associated with cardiac malformations leading to
      pulmonary hypertension. Acquired aneurysms can be idiopathic or associated with
      infections (tuberculosis, syphilis), trauma, pulmonary valvular stenosis, or
      collagen diseases. Pulmonary artery aneurysms are not common and an idiopathic
      pulmonary artery aneurysm is a rare finding that could be diagnosed incidentally.

PMID- 22145275
TI  - Brain infarction as the initial presentation of primary posterior mediastinal
      seminoma.
AB  - A 40-year-old man was admitted with acute onset of slurred speech and right
      hemiparesis. Cerebral infarction was diagnosed from magnetic resonance (MR)
      images. Chest X-ray incidentally revealed a posterior mediastinal tumour, which
      proved to be seminoma on CT-guided biopsy. The patient then received
      chemotherapy. Five months later, right upper limb weakness and slurred speech
      occurred again. Brain MR images revealed two metastatic lesions in the prior
      infarct areas, which on histology proved to be metastatic seminoma.

PMID- 22145276
TI  - Phialemonium curvatum fungaemia in an immunocompromised patient: case report.
AB  - Although infections due to fungal pathogens are rare, the incidence of such
      infections has increased over the last few decades, mainly because of growing
      populations of immunocompromised patients. We report a case of a Phialemonium
      curvatum fungaemia in a woman with a history of a peripheral stem-cell
      transplantation. The case is analysed with 20 other cases described in the
      literature since 1986. Adequate therapeutic management is becoming increasingly
      important for immunode-pressed patients, in light of a broadened therapeutic
      choice of antifungals. Therefore precise and timely identification of fungi is
      needed. Therapeutic options with regard to Phialemonium fungaemia are also
      discussed.

PMID- 22145277
TI  - Hemiballism revealing type 2 diabetes in an elderly: clinical and neuroimaging
      findings and etiopathogenic links.
AB  - Hemiballism-hemichorea is characterized by non-patterned and involuntary
      unilateral movements. It is a rare clinical sign unmasking type 2 diabetes
      mellitus, mostly in elderly patients. We report the clinical and neuroimaging
      findings of a patient admitted for hemiballism-hemichorea of the right upper
      limb, leading to the diagnosis of type 2 diabetes. We hereby describe clinical
      and neuroimaging findings. After initiation of treatment and restoration of
      euglycaemia, we note a complete remission of the initial neurological symptoms.

PMID- 22145278
TI  - Metformin-associated lactic acidosis (MALA): case report.
AB  - Metformin is the first-line therapy for the treatment of diabetes mellitus. In
      certain conditions lactic acidosis (MALA) can occur. Starting with a case report
      of a 62-year-old woman presenting with abdominal pain, we bring this complication
      to attention, describing its pathogenesis and its management. This underlines the
      need for thoughtful use of metformin.

PMID- 22145279
TI  - Case report: Aortoduodenal fistula presenting as iron-deficiency anaemia.
AB  - Aortoenteric fistulae are a rare cause of gastrointestinal bleeding. If
      undiagnosed, mortality is high. The outcome of aortoenteric fistula has improved
      significantly due to better diagnostic modalities, advances in anaesthesia and
      surgical techniques including endovascular aortic repair. Early diagnosis
      requires a high index of clinical suspicion. An aortoenteric fistula should be
      suspected in every patient with a history of surgical or endovascular repair of
      aortic disease who presents with gastrointestinal bleeding. Most patients present
      with massive gastrointestinal bleeding. Presentation with iron-deficiency anaemia
      on routine blood analysis, as in our case report, is extremely unusual.

PMID- 22145280
TI  - Severe imported plasmodium vivax malaria as a cause of pseudohypereosinophilia.

PMID- 22145281
TI  - HIV-associated lymphoid interstitial pneumonia mimicking miliary tuberculosis.

PMID- 22145282
TI  - Duplicate gallbladder: an unusual presentation.

PMID- 22145283
TI  - A case of Takotsubo syndrome.

PMID- 22145285
TI  - Ramping up robotics. Raising awareness of robotic technology helps one hospital
      gain the competitive edge.

PMID- 22145284
TI  - Hypokalaemic paralysis with seemingly pH-neutralized blood gas: liquorice-induced
      mineralocorticoid effect superimposed on renal tubular acidosis.

PMID- 22145286
TI  - The patient connection. By tapping into the power of technology, providers can
      empower patients and improve the quality of care.

PMID- 22145287
TI  - Beyond brochures. Health care marketing today is about more than slick ads. It's
      about engaging with communities.

PMID- 22145288
TI  - Plan for success. An effective planning cycle can reap big rewards.

PMID- 22145289
TI  - Go climb a tree. How Arkansas Children's Hospital used "natural" marketing to re
      launch its website.

PMID- 22145290
TI  - Time for answers. One insurer is working to move the conversation about rising
      health care costs beyond looking for scapegoats to finding solutions.

PMID- 22145291
TI  - Going mobile? Smartphone marketing efforts just make sense.

PMID- 22145292
TI  - How effective is your board? Boards of directors play a more important role than
      ever.

PMID- 22145293
TI  - The magic of walking. Make walking a part of your organization's culture.

PMID- 22145294
TI  - [Non invasive ventilation in the preterm infant].

PMID- 22145295
TI  - Pattern of cerebral ultrasound in neonatal heart surgery.
AB  - AIM: No study described reliably the changes in cerebral ultrasound (CUS)
      findings in neonatal heart surgery. We tried to define the modifications of CUS
      before and after heart surgery in neonates. PATIENTS: We studied 48 neonates with
      congenital heart defects were studied. Of these, 33 had correction of the
      malformation with cardiopulmonary bypass (CPB group); 15 underwent coarctation
      repair/shunting procedures (no-CPB group). Patients had CUS pre-operatively, 48
      72 hours after surgery, and at discharge. RESULTS: Pre-operative studies did not
      show significant differences between the groups. In CPB group, preoperatively,
      6/33 infants showed echogenicity of basal ganglia and 1/33 grade I IVH. In the
      early postoperative evaluation, 24/33 infants had abnormal scans: increased
      echogenicity of basal ganglia in 24 and grade I IVH in 14. At discharge, abnormal
      scans persisted in 20/33 (basal ganglia echogenicity in 20, grade I IVH in 12).
      In the no-CPB group, preoperatively, 1/15 infant showed echogenicity of basal
      ganglia. In the early postoperative evaluation, 6/15 had abnormal scans:
      increased echogenicity of basal ganglia in 6, grade I IVH in 4. At discharge,
      abnormal scans persisted in 3/15. CONCLUSIONS: CUS after neonatal heart surgery
      shows a definite pattern of increased echogenicity of the basal ganglia, more
      consistent after CPB. These changes may reflect disturbances of deep grey matter,
      and last 10-15 days at least.

PMID- 22145296
TI  - Congenital ptosis and blefarophimosis: retrospective analysis of the
      effectiveness of correction with levator resection and frontalis suspension.
AB  - BACKGROUND: treatment of congenital ptoses and blepharophimoses relies on levator
      resections and frontalis suspensions. Several techniques of levator resection
      have been described in literature, some of them include tarsal resections and
      resections of the Muller muscle. Nevertheless a gold treatment have not been
      detected yet. Frontalis suspension is performed when levator muscle is not
      functional or when ptosis is severe. The suspension could be carried out with
      several materials: ePTFE, silicon rods, poly-propylene, nylon, braided poliester,
      but the preferable material is considered the autologous fascia lata. AIMS: this
      study was designate to determine retrospectively if the indications of surgery
      are correct, considering age, severity of pathology, relapses and complications.
      An analysis of demographic data and outcomes for each technique is performed.
      METHODS: in this study we analyze case series of 33 pediatric patients affected
      by congenital ptosis and blepharophimosis congenital syndrome, surgically treated
      from 2000 to 2008 in the ophtalmic pediatric surgery department at the Niguarda
      Hospital of Milan. A literature review was also performed. RESULTS: the mean age
      at presentation was 4.13. The diagnosis was precocious in most cases and often
      helped by some recognizable clinical signs: compensatory head posture (48.5%),
      anisometropia (36.4%), astigmatism (48.5%), strabismus (36.4%) and amblyopia
      (15.2%). Most of patients was treated with frontalis suspension (57.6%) and their
      age was significatively lower than patients treated with levator resection. No
      difference about complications and recurrence was reported between the two
      techniques. Complications and recurrence amount to 39.4%. CONCLUSION: these
      results are in line with other studies in literature. A precociuos treatment is
      able to reduce the incidence of amblyopia from 34% to 8%. The choice of the
      treatment (resection Vs suspension) has to consider the age of the patient, the
      severity of ptosis and avaibility of fascia lata. Nevertheless no significative
      difference in outcomes have been demonstrated between the two techniques.

PMID- 22145297
TI  - Posterior urethral polyp causing haematuria in children.
AB  - Posterior urethral hemangioma (PUH) is a rare congenital lesion, included in
      group of polypoid or papillary lesion of the prostatic urethra. This lesion is
      responsible for a variety of symptoms in children that may be associated or
      isolated, sometimes its finding is occasional. The diagnosis is usually made by
      ultrasonography and cystourethrogram, but the gold standard is represented by the
      urethrocystoscopy with double possibility: diagnostic and therapeutic. The
      Authors report a case of 1-year-old boy with persisting haematuria, in whom a
      previews cystoscopy didn't find any cause of haematuria. An accurate
      urethrocystoscopy let to make diagnosis of prostatic urethral polyp, a
      transurethral resection was performed and pathological assessment confirmed the
      diagnosis of PUH.

PMID- 22145298
TI  - [Treatment of gastrointestinal bleeding in neonates: a case report].
AB  - Gastrointestinal bleeding in infants and children is an uncommon and potentially
      serious problem, but fortunately is usually limited and most cases resolve with
      close medical attention. The therapeutic criteria is often difficult particularly
      in neonates. In this work we examine the case of a neonate with serious
      gastrointestinal bleeding and the delayed treatment for diagnostic difficulties.

PMID- 22145299
TI  - Mesenteric cystic lymphangioma associated with intestinal malrotation in a
      newborn.
AB  - Mesenteric cystic lymphangiomas are uncommon benign cystic tumors rarely
      associated with other congenital malformations. We herein describe a case of a 9
      day-old female presented with a two-day history of bilious vomiting, feeding
      intolerance, weakness and lethargy. Preoperative studies were diagnostic of
      intestinal malrotation. At laparotomy a cystic mesenteric mass was identified.
      Histopathological examination confirmed the diagnosis of mesenteric cystic
      lymphangioma. The exact aetiology of mesenteric lymphangioma is unknown and this
      case supports the theory that lymphangioma is a primary congenital malformation.

PMID- 22145300
TI  - [The use of ondansetron in acute gastroenteritis. Its impact in a pediatric
      emergency department].
AB  - BACKGROUND: Ondansentron is in consideration in literature for its use in
      vomiting secondary to acute gastroenteritis in children. OBJECTIVE: To evaluate
      its usefulness in children with acute gastroenteritis referred to a paediatric
      emergency department. METHODS: A retrospective study considered 967 children
      treated with ondansetron (0,06 mg/kg IM) plus oral rehydration, with a control
      group of 286 children who received only oral rehydration. RESULTS: The time spent
      into the short-stay observation unit and the total emergency department stay were
      significantly reduced in children receiving ondansentron. No adverse reactions to
      the drug were recorded.

PMID- 22145301
TI  - Congenital ptosis.

PMID- 22145302
TI  - [Yeast prions as a model of neurodegenerative infectious amyloidoses in humans].
AB  - Several neurodegenerative diseases (so-called age-related diseases) in humans are
      associated with development of protein aggregates--amyloids. Prion diseases-
      kuru, Kreutzfeldt-Jakob and Gerstmann-Straussler-Sheinker diseases, fatal
      familial insomnia, etc.--are examples of infectious amyloidoses. A model system
      for investigation of mechanisms of amyloidogenesis and of its infectious nature
      had been developed as a result of yeast prion discovery. The existence of a prion
      network as an interaction of different prions identified in yeast is being
      confirmed recently as an interaction of different anyloids in humans. The
      potential danger of amyloidoses is conditioned by the very structure of almost
      all proteins containing fragments capable to be organized as beta-sheets, which
      lead to their aggregation being exposed. Meanwhile, there are several well
      defined examples of the adaptive value of amyloid aggregates: cytoplasmic
      incompatibility factor in Podospora anserina, spider silk, cytoplasmic stress
      granules in mammals, prion form of CPEB protein responsible for the neuron
      activity in Aplisia, etc. These facts should be taken into consideration when
      seeking antiamyloid drugs. Discovery of protein inheritance in lower eukaryotes
      modifies our knowledge of the template principle significance in biology and adds
      a concept of conformational templates (II order templates) involved in
      reproduction of the three-dimensional structure of the supramolecular complexes
      in the cell.

PMID- 22145303
TI  - [Statistical study of rapid mechanodependent cell movements in deformed explants
      of African clawed frog Xenopus laevis embryonic tissues].
AB  - Computer analysis of artificially deformed (stretched or compressed) double
      explants (sandwiches) of the blastocoel roof (BRs) and suprablastoporal region
      (SBRs) of African clawed frog Xenopus laevis early gastrula has been performed
      using frames of time-lapse microfilming. During the first 14 min after cutting
      off, the velocities and displacement angles of several hundreds of cells relative
      to one another, as well as to fixed points and the extension axis, were measured
      in the control and deformed samples. It has been found that the deformation of
      samples leads to a rapid reorientation of large cell masses and increase in the
      velocities of movements along the extension axes or perpendicularly to the
      compression axes. In addition, an increase in the velocities of mutual cell
      displacements in the stretched BRs and cell convergence to the extension axes
      have been observed. Comparison of different angular sectors demonstrates a
      statistically significant positive correlation between the mean velocities of
      cell movements and the number of cells moving within an individual sector. This
      suggests cooperativity of mechanodependent cell movements. In general, these
      results demonstrate an important role of mechanical factors in regulation of
      collective cell movements.

PMID- 22145304
TI  - [Activation of cell division in the quiescent center of excised maize root tip].
AB  - The phenomenon of activation of cell proliferation in the quiescent center of
      excised maize roots is described. The root tips were grown on wet filter paper in
      Petri dishes. This phenomenon was observed in 8 to 14 maize cultivars and was
      absent in excised Arabidopsis root tips. The distribution of mitoses in meristems
      greatly varied in roots of individual seedlings from the same seed lot and
      seedlings of different cultivars. Meristem opening was observed after the removal
      of small root tips not longer than 3 mm and intact seminal roots. Sucrose (2%)
      and 10(-6)-10(-8) M indole-3-acetic acid did not prevent meristem opening. These
      findings indicate that the state of quiescent center is maintained by a system of
      intercellular and interorgan relations, which are to be clarified.

PMID- 22145305
TI  - [Properties of norm and variability].
AB  - Data of the authors from many years on the two ways of development of a group of
      offspring of tailless amphibians--development with the effect of the norm of
      characteristics and development with the effect of mass anomalies of a number of
      characteristics--are summarized. Mass anomalies of limbs in the African clawed
      frog Xenopus laevis were obtained in laboratory (without using any special
      influences). They represent a syndrome when the structure of limbs and their
      girdles, as well as the sacral part of the spine, change correlatively. The
      syndrome has several stages of manifestation (according to the degree of
      intensification of deviations from the norm). The maximum manifestation of the
      syndrome produces a change in the norm of the structure of the sacral part. It
      was shown that change in the rule of its variability precedes change in the norm
      of the structure of the sacrum. Not having an opportunity of observing the
      process of evolution directly (change in norms on the large scale of time), we
      have to use any data (even indirect), which can give us information on how the
      change in the norm takes place and what happens to the variability.

PMID- 22145306
TI  - [Crucial stages of embryogenesis of R. arvalis: Part 1. Linear measurements of
      embryonic structures].
AB  - Investigations of individual variability have allowed us to reveal the crucial (=
      nodal) stages in embryogenesis of the moor frog (Rana arvalis Nills.). These
      crucial stages are: the late gastrula stage (stages 18-20), the hatching stages
      (stages 32-33) and, apparently, early metamorphosis (stage 39). Moreover, we have
      found that each embryonic structure passes through its specific crucial stages.
      For example, stage 34 is crucial for the trait "tail width" but is internodal for
      all other embryonic traits. At this stage, larva passes from an attached to a
      free-swimming life style. We also found considerable differences between the
      different frog populations in the the level of developmental variability. These
      differences were associated with internodal developmental stages.

PMID- 22145307
TI  - [Effect of exogenous factors on the induction of spicule formation in sea urchin
      embryonic cell cultures].
AB  - The effect of exogenous factors on the realization of the spicule formation
      program in two sea urchin species, Strongylocentrotus intermedius and S. nudus,
      has been studied in primary embryonic cell cultures derived from the blastula and
      gastrula stages. It has been shown that the process of spicule formation depends
      on the type of substrate and the composition of the medium. An original finding
      is that calf or horse serum necessary for spicule formation in vitro can be
      replaced by a complex of factors including insulin, transferrin, and lectins.
      Methods allowing control over the growth and differentiation of marine
      invertebrate embryonic cells in vitro open prospects for their application to
      practical problems such as the establishment of cell cultures producing certain
      mineral structures.

PMID- 22145308
TI  - [Network, cellular and molecular mechanisms of plasticity in simple nervous
      systems].
AB  - In the present study we will try to single out several principles of the nervous
      system functioning essential for describing mechanisms of learning and memory
      basing on our own experimental investigation of cellular mechanisms of memory in
      the nervous system of gastropod molluscs and literature data: main changes in
      functioning due to learning occur in effectivity of synaptic inputs and in the
      intrinsic properties of postsynaptic neurons; due to learning some synaptic
      inputs of neurons selectively change its effectivity due to pre- and postsynaptic
      changes, but the induction of plasticity always starts in postsynapse,
      maintaining of long-term memory in postsynapse is also shown; reinforcement is
      not related to activity of the neural chain receptor-sensory neuron-interneuron
      motoneuron-effector; reinforcement is mediated via activity of modulatory
      neurons, and in some cases can be exerted by a single neuron; activity of
      modulatory neurons is necessary for development of plastic modifications of
      behavior (including associative), but is not needed for recall of conditioned
      responses. At the same time, the modulatory neurons (in fact they constitute a
      neural reinforcement system) are necessary for recall of context associative
      memory; changes due to learning occur at least in two independent loci in the
      nervous system. A possibility for erasure of memory with participation of
      nitroxide is experimentally and theoretically based.

PMID- 22145309
TI  - [The role of fast and slow potassium currents in electrical activity of amphibian
      myelinated nerve fibres].
AB  - The paper reviews the information about the role of fast and slow potassium
      currents in electrical activity of amphibian myelinated nerve fibres. It
      demonstrates the importance of discovering of fast and slow potassium currents
      and their following pharmacological separation (by potassium channels blockers 4
      aminopyridine and tetraethylammonium) in investigation of mechanisms of
      biological potentials generation. The information about the existence of fast and
      slow potassium channels in the nerve membrane and about the properties of 4
      aminopyridine and tetraethylammonium action served as a base for determination
      the nature of biological potentials and discovering the mechanism of potential
      dependent action of 4-aminopyridine that for tens of years suffered from the lack
      of adequate explanation.

PMID- 22145311
TI  - [Prolactin osmoregulatory function in fishes and its projection on mammals].
AB  - Prolactin evolution and key role in fish osmoregulation were reviewed. Comparison
      of fish and mammalian prolactin was made in respect of its structure, producing
      tissues, regulation of pituitary secretion. Peculiarities of prolactin receptor
      structure and prolactin-induced signal cascades, tissue distribution and
      regulation of prolactin receptor expression were compared in fishes and mammals.
      Data on mechanisms of prolactin action on ionoconservation in teleost fishes at
      the level of gills, kidney, intestine, and skin were presented. The facts of
      prolactin participation in the regulation of water and salt balance in mammals
      were observed. The existence of fundamentally similar mechanisms of
      osmoregulatory prolactin action in fishes and mammals was accumed and algorithm
      of their investigation was suggested.

PMID- 22145310
TI  - [Recent data about the role of hypothalamic suprachiasmatic nucleus in circadian
      organization of physiological functions].
AB  - The suprachiasmatic nucleus is the primary circadian pacemaker in mammals. In
      turn, the suprachiasmatic nucleus influences circadian physiology, endocrinology
      and behavior via the synchronization of local oscillators that are operative in
      the cells of most organs and tissues. Thus circadian pacemaker may play an
      important role in psychiatric disorders and in psychotherapeutic drugs effect. In
      this review, we summarize data about the suprachiasmatic nuclei anatomy,
      physiology and pharmacological sensitivity.

PMID- 22145312
TI  - [Two-nuclear neurons: sincitial fusion or amitotic division].
AB  - In the review the history of research two-nuclear neurons is stated and two
      hypotheses about mechanisms of their formation are analysed: by sincitial fusion
      or amytotic divisions. The facts of discrepancy of the former orthodox cellular
      theory categorically denying possibility sincitial of communications in nervous
      system and of sincitial fusion neurons are mentioned. As an example results of
      ultrastructural researches of occurrence sincitium in a cortex of the big brain
      of rats, in autonomic ganglions, in hypocampus and a cerebellum of adult animals
      are presented. The video data of the sincitial fusion of live neurons and the
      mechanism of formation multinuclear neurons in tissue culture are analyzed.
      Existing data about amytotic a way of formation two-nuclear neurons are
      critically considered. The conclusion becomes, that the mechanism of formation
      two-nuclear neurons is cellular fusion. Simultaneously the review confirms our
      representations about existence in nervous system sincitial interneural
      communications.

PMID- 22145313
TI  - [Functional metabolic characteristics of sodium hyaluronate in mammal organism].
AB  - In the review data concerning functional metabolic characteristics of sodium
      hyaluronate in mammal organism, as well as autologous results concerning the
      study of its intraarticular action on metabolism of conjunctive tissue in the
      conditions of experimental arthritis in rabbits are given.

PMID- 22145314
TI  - [Effect of inorganic fluorine on living organisms of different phylogenetic
      level].
AB  - The presented review summarizes literature data on pathways of the inorganic
      fluoride intake into the plant, animal, and human organisms, on its metabolism,
      distribution, and accumulation in the organism, forms of fluoride in biological
      tissues, toxic effects of fluoride on physiological and reproductive functions of
      living organisms of various phylogenetic groups, as well as clinical symptoms of
      deficient and excessive fluoride intake into the human organism.

PMID- 22145315
TI  - [Biochemical and genetic aspects of pathogenesis of schizophrenia].
AB  - Some molecular-biological and genetic concepts of development of schizophrenia
      are discussed. The main attention is paid to the ontogenetic aspect of
      dopaminergic disturbances and to role of risk factors, including stress,
      responsible for interaction between the nervous, endocrine, and immune systems
      during development of schizophrenia.

PMID- 22145316
TI  - [Quaternary phosphonium reversibile inhibitors of cholinesterases of different
      animals].
AB  - Quaternary phosphonium compounds were found to be reversible inhibitors of
      cholinesterases of various animals and showed species-specificity of action
      depending on the inhibitor structure. It became possible to reveal difference in
      inhibitory specificity of various preparations of acetylcholinesterases. A
      difference has been shown in inhibitory parameters of the series of phosphonium
      toward cholinesterase of visual ganglia of individuals of the squid Berryteuthis
      magister from different zones of the habitat areal. For the first time, when
      comparing phosphonium and ammonium isologues - tetrabutyl- and tributylhe-xyl
      derivatives, it has been shown that they are agents practically similar by the
      character of anticholinesterase action.

PMID- 22145317
TI  - [Lipid composition of cells and low-density lipoproteins in blood serum of humans
      and some vertebrates species].
AB  - To investigate interaction of atherogenic low-density lipoproteins (LDL) with
      erythrocytic membrane, the content of lipid components in blood cells and serum
      LDL was studied in human in norm (donors) and in 12 species of vertebrates (the
      mammals non-predisposed to atherosclerosis - birds and fish). Lipid composition
      of blood cells and LDL was analyzed also in patients with pathologies: ischemic
      heart disease (IHD), bronchial asthma (BA), and chronic obstructive bronchitis
      (COB), and in 2 species of mammals predisposed to atherosclerosis, in whose blood
      LDL predominates. The content of lipids in cells and LDL of the studied
      vertebrates has been found to depend on their taxonomy and the clear trends both
      to an increase of the cholesterol content and to a decrease if the
      phosphatidylcholine level in patients, particu- larly with IHD, and on a rise of
      the ratio of the content of the more saturated sphingomyelin and cholesterol to
      the less saturated phosphatidylcholine from the lower to the higher organisms,
      including humans (donors). The highest levels of free cholesterol in blood cells,
      of total cholesterol in LDL, and of ration of the cholesterol/phosphatidylcholine
      content have been revealed in patients, especially with 1HB, and in the mammals
      predisposed to atherosclerosis, i. e., in representatives with predominance of
      blood LDL, unlike donors and the mammals resistant to atherosclerosis. The
      highest parameters of lipid components were determined in cells and LDL inhuman
      with IHD. The lipid LDL composition affects directly the composition and ratio of
      lipids in blood cells.

PMID- 22145318
TI  - [Dependence of protective effect of alpha-tocopherol on its concentration and
      time of action on PC12 cell under conditions of oxidative stress].
AB  - At the short-term incubation (0.5 and 1.5 h) of cells of the PC12 neuronal line
      with alpha-tocopherol, its protective effect against the cytotoxic hydrogen
      peroxide action was increased with rise of its concentration in samples; the
      protection was practically absent at action of nanomolar antioxidant
      concentrations, but was well expressed at its micromolar concentrations. These
      data agree with the concept that alpha-tocopherol increases the cell living
      activity by reacting directly with free radicals, which leads to formation of the
      less reactive compounds deprived of non-paired electron. The evidence is obtained
      that at the long-term action on PC12 cells, alpha-tocopherol not only in micro-,
      but also in nanomolar concentrations increases statistically significantly the
      cell living activity under conditions of oxidative stress. As follows from the
      obtained data, an important role in realization of the alpha-tocopherol
      protective effect at the long-term incubation with it seems to be played by
      modulation by this antioxidant of activity of protein kinase activated by
      extracellular signaling, phosphatidylinosite 3-kinase, and protein kinase C.

PMID- 22145319
TI  - [Bounds of change in unsaturation index of fatty acid composition of
      phospholipids at adaptation of molluscs to biogenic and abiogenic factors of
      external medium].
AB  - Comparative study of fatty acid composition of total phospholipids, as well as of
      phosphatidylcholine and phosphatidylethanolamine from hepatopancreas and leg
      muscle was performed on several representatives of gasteropods (Gastropoda)
      molluscs and bivalve (Bivalvia) mussel (Mytilus edulus). The objects of our study
      were marine litorins (Littorina saxsatilis) adapted to different temperature
      conditions of White Sea and Barents Sea, freshwater lymnaea (Lymnaea stagnalis)
      infested by Trematoda and mussels from White Sea and Black Sea. It was shown that
      depending on the existence conditions of studied tissue or lipid, the maximal
      change is observed in the percentage of saturated acids (4-83 %), the percentage
      of unsaturated acids was less expressed (1-14 %) and the changes in unsaturation
      index (UI) did not exceed 20 % on average. It was supposed that observed
      quantitative bounds of UI change under the action of different external factors
      is utmost for maintenance of membrane fluidity necessary for normal vital
      activity of cell, particularly in studied ectothermic molluscs.

PMID- 22145320
TI  - [Sexual dimorphism in photoperiodical plasticity of body mass in the green dock
      leaf beetle Gastrophysa viridula].
AB  - Sexual dimorphism in body mass was studied in prepupae, pupae and immature adults
      of the green dock leaf beetle Gastrophysa viridula under a constant temperature
      of 24 degreesC and two photoperiods (12L: 12D and 22L:22D). Females were
      significantly heavier compared to males at all the three developmental stages;
      just after emergence from pupae they weighed on average 11.4 mg while males -10.3
      mg. Sex differences in photoperiodic body mass plasticity were revealed: under
      short-day conditions pupal and adult mass in females was significantly higher
      compared to long day, but not in males. Such a response to short day (the factor
      inducing reproductive diapause in this species) is likely to promote accumulation
      of greater amount of nutrients by females which is necessary for earlier
      oviposition after over-wintering.

PMID- 22145321
TI  - [Immunohistochemical investigation of Bcl-2 and p53 levels in rat hypothalamus
      after sleep deprivation].
AB  - On Wistar rats in view of electrophysiological parameters after sleep deprivation
      (SD; awake by gentle handling method) and the subsequent postdeprivative sleep
      (PDS) immunohistochemical investigation of Bcl-2 and p53 peptides optical density
      levels in neurons of paraventricular (PVN), supraoptic (SON) and median (MnPN)
      hypothalamus nuclei was carried out. The Bcl-2 was increased in all nuclei both
      after SD and PDS. The level of p53 was increased in PVN and SON after SD and PDS,
      but in MnPN only on PDS. Any morphological attributes of apoptosis in the nuclei
      was not revealed. Obtained data testify an active role of p53 and Bcl-2 peptides
      in regulation of neuronal activity in hypothalamus at change of a cycle
      wakefulness-sleep.

PMID- 22145322
TI  - [Cardiovascular manifestations of acute nitrite intoxication in laboratory rats].
AB  - The systemic and peripheral hemodynamics was studied in male white rats under
      conditions of acute nitrite hypoxia (subcutaneous administration of sodium
      nitrite at doses of 1, 3, and 5 mg/100 g body mass). By the electrocardiographic,
      rheographic, and other methods there were recorded the heart rate (HR), minute
      circulation volume (MCV), cardiac output (CO), skeletal muscle circulation (SMC),
      brain circulation (BC), and systemic arterial pressure (AP). Nitrite was shown to
      produce a fast, dose-dependent AP decrease accompanied by a decrease of MCV due
      to development of bradycardia and a fall of CO. At the phase of the steady
      hypotension, CO increased due to a significant rise of CO on the background of
      the continuing bradycardia. The systemic circulatory effects of NaNO2 were found
      to be accompanied by a redistribution of peripheral circulation in the form of a
      dose-dependent increase of BC and a sharp fall of MCV. It was shown that 1-1.5 h
      after the nitrite injection the parameters of systemic and peripheral
      hemodynamics approached the initial levels. Possible triggering mechanisms of the
      initial stage of the rat cardiovascular adaptation to conditions of acute nitrite
      hypoxia are discussed.

PMID- 22145323
TI  - [Effect of individual peculiarities on formation of preference of ethanol in
      female and male Wistar rats].
AB  - Individual characteristics of animal behavior can serve a prognostic parameter of
      predisposition to use of alcohol. The goal of the work was to study dynamics of
      formation of preference of alcohol at early stages in the process of forced
      alcoholization in male and female rats as well as the accompanying changes in
      behavior parameters. For 3 months, the rats were submitted to the forced
      alcoholization with 10 % ethanol. Each week the rats were tested in the "two
      glass trial". Individual peculiarities of all animals were evaluated prior to,
      after 6 weeks, and after the end of the experiment with aid of the "open field
      test" and "Suok-test". Results showed that the male rats demonstrating by the end
      of the experiment the significantly higher level of the alcohol preference, at
      the initial stages of the forced alcoholization demonstrated the significantly
      lower preference as compared with the remaining ones. These rats also showed the
      lower levels of the motor and exploratory activities before alcoholization as
      compared with control. On the contrary, the individuals that by the end of the
      experiment did not differ from control by the level of the alcohol preference
      demonstrated prior to alcoholization in the "Suok-test" the higher anxiety level.
      In female groups, no statistically significant differences were observed both in
      parameters of the motor and exploratory activities and in the anxiety level in
      both tests. Thus, in male rats, the prognostic parameter predicting formation of
      the abuse can serve the degree of alcohol preference at the initial stages.

PMID- 22145325
TI  - [Characteristics of spreading action recorded in various sites of skeletal muscle
      fibers of the frog Rana temporaria].

PMID- 22145324
TI  - [Convergence of modulating influences of presynaptic metabotropic glutamate and
      GABAB receptors].

PMID- 22145326
TI  - [Serotoninergic modulation of synaptic transmission in dorsolateral nucleus of
      rat amygdala].

PMID- 22145327
TI  - Homeostatic changes of short-term plasticity of gabaergic synaptic transmission
      in rat hippocampal cell cultures.
AB  - It is well documented that prolonged alteration of activity in neuronal networks
      initiates a number of homeostatic mechanisms including compensatory changes of
      excitatory and inhibitory synaptic strength. We studied whether this also evokes
      compensatory changes of short-term synaptic transmission. Using patch-clamp
      technique in hippocampal cell cultures we examined the effects: of prolonged
      decrease of neuronal firing evoked by sodium channel blocker: tetrodotoxin (TTX)
      and ionotropic glutamate receptor antagonist - kynurenate; prolonged enhancement
      ofneuronal firing evoked by antagonist GABAA receptors - bicuculline on short
      term depression of GABAergic synaptic transmission evoked by train of stimuli (5
      Hz). We found that both TTX and kynurenate treatments enhance depression of
      GABAergic transmission, while bicuculline treatment does not. We conclude that
      alteration of depression of GABAergic transmission evoked by the prolonged
      decrease of neuronal activity may contribute to homeostatic plasticity in
      hippocampal neuronal networks.

PMID- 22145328
TI  - [Sleep and pregnancy].
AB  - Sleep disturbances are frequent during pregnancy and are currently regarded as
      one of the most important factors determining pregnancy outcome. Detailed
      research of sleep features during pregnancy is obviously essential. In the
      present review recent data concerning changes in sleep structure and regulation
      in pregnant women and rats - main subjects of experimental sleep research, are
      given, including surmised mechanisms underlying such changes. The importance of
      women's sleep integrity preservation during pregnancy for the viability and
      normal development of the fetus is emphasized and possible ways of pathological
      influence of sleep disorders during this period are discussed.

PMID- 22145329
TI  - [Optimal signal filtering parameters for tetrode recording of neuronal activity].
AB  - Extracellular recording of neuronal spiking is the main method of investigation
      of involvement of neurons in behavioral tasks. Development of multichannel
      electrodes made it possible to simultaneously record activity of the same group
      of neurons from different locations in the brain tissue. That method allows the
      researches to distinguish spiking of simultaneously recorded neurons by
      individual set of projection coefficients of amplitude parameters on axes
      corresponding to different channels of the multichannel electrode. We tested the
      possibility of effective separation of single unit spiking streams from multiunit
      activity recorded by tetrode and subjected to different filtering. We described
      the main limitations for effective spike identification and determined the
      optimal band of signal filtering for tetrode recording.

PMID- 22145330
TI  - [Features of the spectral power of the EEG rhythms in autistic children and their
      relation with the progress of different symptoms in schizophrenia].
AB  - Right hemispheric dominance of the baseline alpha-band spectral power was
      revealed in 5-7 years boys with autism. This feature persisted during performance
      of a cognitive task (counting). Also, boys with autism showed lowered level of
      the alpha spectral power as compared with healthy children. In healthy children,
      the gamma spectral power increased during performance of the cognitive task as
      compared to baseline state. Autistic persons showed higher values of the gamma
      spectral power as compared with normal boys. Boys with autism showed less
      expressed changes in the gamma spectral power during the cognitive task than
      healthy children. The reduced spectral power of the alpha band in autistic boys
      may serve as a precursor of conversion from autism to schizophrenia. Higher level
      of the gamma spectral power in autistic boys is characteristic also of
      schizophrenic patients with positive symptoms. Lowered levels of fast rhythms
      reactivity revealed in autistic boys and the same effect earlier described in
      schizophrenic adults probably have the similar nature.

PMID- 22145331
TI  - [Activation of brain structures by fMRI data when viewing the video clips and
      recall of shown actions].
AB  - In 10 healthy volunteers, brain tomograms were recorded using an fMRI scanner
      with a 3T-field magnet. Emotionally neutral and emotionally involving videos were
      used for stimulation. Registration consisted of seven series: two series of
      viewing a fixation point and two kinds of video clips, one series of viewing of a
      succession of two types of video clips, two series of watching videos with
      subsequent recall, and two series of viewing the fixation point followed by
      recall of content online. Viewing content online caused the greatest degree of
      metabolism increase localized in the visual cortex. This activation was more
      pronounced during the presentation of an emotionally involving video clip. In
      addition to the occipital lobe, it actively involved the temporal, parietal and,
      to a lesser extent, the frontal cortex. Activation of the motor cortex was
      detected only in some subjects. The "interference" effect in which the increase
      in metabolism was minimal was observed during a consequent demonstration of video
      clips. Immediate recall of video-clips after viewing caused the greatest
      activation of the posterior frontal and motor cortex. Delayed recall activated
      mostly the anterior frontal cortex. There was a decrease of metabolism in the
      visual cortex during the recall. The greatest reduction in the visual cortex was
      observed during immediate recall. Immediate and delayed recall activated the
      structures associated with the maintenance of consciousness, memory and a system
      of mirror neurons.

PMID- 22145332
TI  - [Influence of "prehistory" of sequential movements of the right and the left hand
      on reproduction: coding of positions, movements and sequence structure].
AB  - The dependence of errors during reproduction of a sequence of hand movements
      without visual feedback on the previous right- and left-hand performance
      ("prehistory") and on positions in space of sequence elements (random or ordered
      by the explicit rule) was analyzed. It was shown that the preceding information
      about the ordered positions of the sequence elements was used during right-hand
      movements, whereas left-hand movements were performed with involvement of the
      information about the random sequence. The data testify to a central mechanism of
      the analysis of spatial structure of sequence elements. This mechanism activates
      movement coding specific for the left hemisphere (vector coding) in case of an
      ordered sequence structure and positional coding specific for the right
      hemisphere in case of a random sequence structure.

PMID- 22145333
TI  - [Some electrophysiological and hemodynamic characteristics of auditory selective
      attention in norm and schizophrenia].
AB  - Six patients in the state of remission after the first episode ofjuvenile
      schizophrenia and seven sex- and age-matched mentally healthy subjects were
      examined by fMRI and ERP methods. The auditory oddball paradigm was applied.
      Differences in P300 parameters didn't reach the level of significance, however, a
      significantly higher hemodynamic response to target stimuli was found in patients
      bilaterally in the supramarginal gyrus and in the right medial frontal gyrus,
      which points to pathology of these brain areas in supporting of auditory
      selective attention.

PMID- 22145334
TI  - [Specific features of regulatory and information-related components of cognitive
      processes in 7-10-year-old children with local EEG abnormalities in the right
      hemisphere].
AB  - Two groups of 7-10-year-old children were formed on the basis of the results of
      visual analysis of their EEG. The first group included 15 children with local EEG
      deviations in the right hemisphere, and the second group included 21 children
      without EEG deviations from the age norm (control group). In both groups, verbal
      and nonverbal higher mental functions and the ability to voluntary control of
      activity were assessed by means of neuropsychological methods. As compared to
      children of the control group, children with local EEG deviations in the right
      hemisphere demonstrated some difficulties in strategy formation, reduced ability
      to maintain already formed programs, increased fatigue, changes in affective
      behavior (anxiety and behavioral excitability), deficit of visual and
      somatosensory perceptual synthesis, reduction in object recognition efficiency,
      and visual memory deficit.

PMID- 22145335
TI  - [Sound improves distinction of low intensities of light in the visual cortex of a
      rabbit].
AB  - Electrodes were implanted into cranium above the primary visual cortex of four
      rabbits (Orictolagus cuniculus). At the first stage, visual evoked potentials
      (VEPs) were recorded in response to substitution of threshold visual stimuli
      (0.28 and 0.31 cd/m2). Then the sound (2000 Hz, 84 dB, duration 40 ms) was added
      simultaneously to every visual stimulus. Single sounds (without visual stimuli)
      did not produce a VEP-response. It was found that the amplitude ofVEP component
      N1 (85-110 ms) in response to complex stimuli (visual and sound) increased 1.6
      times as compared to "simple" visual stimulation. At the second stage, paired
      substitutions of 8 different visual stimuli (range 0.38-20.2 cd/m2) by each other
      were performed. Sensory spaces of intensity were reconstructed on the basis of
      factor analysis. Sensory spaces of complexes were reconstructed in a similar way
      for simultaneous visual and sound stimulation. Comparison of vectors representing
      the stimuli in the spaces showed that the addition of a sound led to a 1.4-fold
      expansion of the space occupied by smaller intensities (0.28; 1.02; 3.05; 6.35
      cd/m2). Also, the addition of the sound led to an arrangement of intensities in
      an ascending order. At the same time, the sound 1.33-times narrowed the space of
      larger intensities (8.48; 13.7; 16.8; 20.2 cd/m2). It is suggested that the
      addition of a sound improves a distinction of smaller intensities and impairs a
      dis- tinction of larger intensities. Sensory spaces revealed by complex stimuli
      were two-dimensional. This fact can be a consequence of integration of sound and
      light in a unified complex at simultaneous stimulation.

PMID- 22145336
TI  - [Cortical network activity before behavioral reaction and before its omission in
      rabbits with defensive dominanta].
AB  - Defensive dominanta was formed in rabbit CNS. Activity of the cortical neuronal
      network was investigated in these rabbits in the state of quiet wakefulness and
      in the intervals between the presentations of testing stimulus (light flashes).
      Statistical analysis of spike trains revealed some distinctions in neuronal
      functional organizations in the excitation focus (sensorimotor cortex) and in the
      visual cortex in the states of quiet wakefulness, before the movement of the paw,
      and before the omission of the reaction. The evidence of different roles in the
      network activity of sensorimotor neurons that responded and not responded to
      light was obtained.

PMID- 22145337
TI  - [Effects of blockade of dopaminergic D1/D2 receptors on behavior of impulsive and
      self-controlled rats].
AB  - Selective antagonists of D1 and D2 receptors (SCH 23 390 and raclopride
      respectively) were injected to rats divided on the basis of preliminary
      experiments into groups of"self-controlled" (preference of valuable but delayed
      reinforcement) and "impulsive" (choice of less valuable but immediate
      reinforcement) animals. Number of omissions of reactions and their latencies were
      recorded. In "self-controlled" rats, both drugs increased the number of reactions
      for less valuable immediate reinforcement, i.e., increased impulsiveness, whereas
      practically did not change the behavior of "impulsive" animals. Introduction of
      SCH 23 390 to animals ofboth groups increased the number of reaction omissions
      the effect being stronger in "self-controlled" animals. Raclopride also increased
      the number of reaction omissions in "self-controlled" rats but only on the next
      day after the injection. In "impulsive" animals, both drugs increased the
      latencies of reactions.

PMID- 22145338
TI  - [Behavioral characteristics of female Wag/Rij rats].
AB  - Behavior of male and female WAG/Rij and Wistar rats was compared in the tests
      assessing the level of anxiety (light-dark choice, open field) and depression
      like state (sucrose intake and preference, forced swimming). Females of WAG/Rij
      rats like males of the same strain exhibited symptoms of depression-like
      behavior: increased immobility in the forced swimming test and decreased sucrose
      intake and preference (anhedonia). In contrast to males, females of WAG/Rij rats
      displayed more distinct signs of increased anxiety as compared to Wistar rats.
      Both WAG/Rij and Wistar females exhibited increased locomotor and exploratory
      activity in the open field as compared to males.

PMID- 22145339
TI  - [Integration of videooculography and encephalography for investigation of visual
      selective attention in humans].
AB  - An original method of EEG recording in combination with eye tracking was
      developed. Due to the precise synchronization (which can include any amount of
      various recording devices), it is now possible to record short-time
      electrophysiological patterns evoked by some visual stimulus. The key feature of
      the method is the possibility to study not only single effects of a stimulus but
      to extract electrophysiological records corresponding to some part of complex
      image scanning.

PMID- 22145340
TI  - [Revealing the genetic determinants of Pks-pathogenicity island in clinical
      strains of enterobacteria].
AB  - AIM: Detection by PCR the frequency of clbB, clbN, clbA H clbQ genes of Pks
      pathogenicity island in clinical strains ofenterobacteria. MATERIALS AND METHODS:
      112 strains various genera and species of enterobacteria, including 16 museum and
      96 clinical are investigated. Isolated strains represents Escherichia species (n
      = 68), Klebsiella (n = 16), Enterobacter (n = 9), Serratia (n = 7) and others
      minor species of Enterobacteriaceae family (n = 12). Fifty nine strains isolated
      from urine of urinary tract infection, 26 isolates from intestines of patients
      with dysbiosis and 11--from children with complications after a liver
      transplantation. A total bacterial isolates were screened by multiplex PCRforthe
      presence ofclbB, clbN, clbA and clbQ genes. RESULTS: Among 41 uropathogenic
      E.coli it is revealed 15 (36,6%) Pks-positive strains carring all of clbB, clbN,
      clbA ? clbQ genes, that composed 27,1% from total number of the enterobacteria,
      isolates from urine. Among 44 clinical isolates of various species of
      enterobacteria only one Pks-positive strain K. pneumoniae was revealed. Strains
      enterobacteria, isolated at pyoinflammatory complications after liver
      transplantation (n = 11) and isolates from intestinal tract in dysbiosis (n =
      26), were Pks-negative. CONCLUSION: The clbB, clbN, clbA ? clbQ genes of the Pks
      island which have been detected in 36,6 % E. coli urological strains are markers
      of pathogenicity of clinical isolates of extraintestinal origin and advisable of
      their detection by PCR.

PMID- 22145341
TI  - [Determination of DNA content in individual Vibrjo cholerae cells by using flow
      cytofluorimetry method: comparative analysis of inhomogeneity in cells of strains
      with various biological properties].
AB  - AIM: Comparative analysis of DNA content in individual cells of Vibrio cholerae
      strains with various biological properties. MATERIALS AND METHODS: 24-hour agar
      cultures of 2 avirulent (lacking cholera toxin gene) and 2 virulent strains and
      their subcultures obtained by cultivation in 1% peptone water for 1, 3 and 5
      hours were studied. DNA of the killed bacteria was dyed by a mixture of ethidium
      bromide and mitramycin. Ratio of cells with low, intermediate and high relative
      DNA content in conditional units of specific DNA fluorescence intensity was
      determined by flow cytofluorimetry method. The degree of inhomogeneity of the
      studied microbial population cells was evaluated by DNA histogram variation
      coefficient value. RESULTS: At the level of major statistical samples of
      individual V. cholerae cells a principally different reaction pattern of the
      studied toxigenic and non-toxigenic strains on changes of cultivation conditions
      was registered. CONCLUSION: Populations of cells of toxigenic V. cholerae strains
      in contrast to non-toxigenic probably shift to polyploid state during starvation.
      This phenomenon may turn out to be a differential feature in determination of the
      risk group (hazard) of a strain.

PMID- 22145342
TI  - [Detection of "hybrid" Vibrio cholerae eltor strains during epidemic
      complications in Syberia and Far East].
AB  - AIM: Biotyping of Vibrio cholerae eltor isolated during epidemic complications of
      cholera in Syberia and Far East by phenotypic and genotypic properties complex.
      MATERIALS AND METHODS: 45 strains of V. cholerae were studied. Phenotypic
      analysis was performed by using a complex ofbiovar determining tests. Genotyping
      was performed by detecting ctxAB, tcpA, toxR, rstRgenes, and ctxB gene structure
      analysis. RESULTS: All the V. cholerae during epidemiologic complications in
      Syberia in the 1970s belong to eltor biovar by phenotypic properties and have
      eltor specific alleles of tcpA and rstR genes, and ctxB of the third genotype in
      the genome. In the 1990s the strains were phenotypically matching eltor biovar,
      but had genetical determinants of both eltor(tcpAE1, rstRE1) and classical
      (ctxB1, rstR(Cl) biovar. CONCLUSION: The cause of epidemic complications of
      cholera in Syberia in the 1970s was V. cholerae eltor with typical eltor
      biovarphenotypical and genotypical properties. In the 1990s cases of introduction
      into the region of "hybrid: V. cholerae eltor strain were ascertained, developing
      into acute cholera outbreaks in several cases.

PMID- 22145343
TI  - [Characteristics of Vibrio cholerae nonO1/nonO139 serogroup strains that caused
      diseases in population of Rostov region].
AB  - AIM: Genotype characteristic and determination of serological properties of
      Vibrio cholerae nonO1/nonO139 strains that caused diseases in population of
      Rostov region from 2000 to 2009. MATERIALS AND METHODS: 15 clinical strains of V.
      cholerae nonO1/nonO139 were studied. Serotyping was performed by using a kit of
      monospecific typing sera against serogroup 02-084 cholera vibrios obtained from
      Rostov Research Institute for Plague Control, PCR and VNTR-genotyping--by using
      specific primers described in scientific publications and constructed by us.
      RESULTS: Serologic features of strains are very diverse and strains contain
      various combination of pathogenicity factor genes that seem to be
      interchangeable. Similar pattern was observed for VNTR-genotyping. Distribution
      of the examined strains by VNTR-genotyping did not correlate with either PCR
      genotyping data or serotyping, or place and time of isolation. CONCLUSION: The
      data obtained indicates a lack of general source of human infection even in the
      same location and time period. On the other hand, serological and genotypic
      features of V. cholerae nonO1/nonO139 may undergo changes in the process of
      staying in the macro organism or environment due to high plasticity of their
      genome.

PMID- 22145344
TI  - [Reasons of low epizootic activity of natural foci of plague in Russia at the
      beginning of the 21st century].
AB  - AIM: Establish the main reasons of low epizootic activity of natural foci of
      plague in Russian Federation in 2000-2009. MATERIALS AND METHODS: Multiyear data
      on the number of isolated Yersinia pestis strains, area of detected epizootic
      sites, amounts of the field material studied for plague were used to evaluate
      annual activity of natural foci. RESULTS: In the current decade mountain and high
      mountain natural foci of plague were characterized by constant high epizootic
      activity. In plains and low-mountain natural foci a low periodic epizootic
      activity was noticed, a development of intra-epizootic periods. A conditioning
      role of helioclimatic factors on the status of parasitic systems and epizootic
      activity of natural foci of plague was noticed. CONCLUSION: The warming of
      climate in 1990-2007 was the main reason for low epizootic activity of plains
      natural foci of plague in Russia. In the contemporary conditions of a recurrent
      cooling (from 2008) and an increase of humidity in the Northern, North-Western
      pre-Caspian and pre-Caucasus territories, a new significant activation of them is
      predicted there with a peak in 2017-2019.

PMID- 22145345
TI  - [Southern taiga combined natural foci of spirochetoses].
AB  - AIM: Study of possibility of existence of combined natural foci of spirochetoses
      (ixodes tick borrelioses and leptospiroses) in typical taiga forests, and their
      etiologic and reservoir-host structure. MATERIALS AND METHODS: Small mammals of
      19 species were captured in 1992-2010 at a station in low-mountain southern taiga
      forests of Chusov area of Perm region. Borreliae were isolated by seeding urinary
      bladder or aural bioptates into BSK II medium, leptospirae--by seeding a
      suspension of kidney tissue into Vervoort-Wolf medium. 1350 animals were studied
      by seeding for borrelia infection and 1077--for leptospira. 287 of those, small
      animals of 6 species, were simultaneously studied for borrelia and leptospira
      infection. Borrelia isolates were identified by using PCR and restriction
      fragment length polymorphism methods, and leptospirae--by using standard
      diagnostic agglutinating sera kit. Blood of 2893 rodents of 12 species and
      insectivorous of 7 species was studied in microagglutination reaction for the
      detection of antibodies against leptospirae. RESULTS: Infection by Borrelia
      garinii and Borrelia afzelii or Grippotyphosa serogroup leptospira was detected
      in 6 most numerous species of forest small mammals. 3 root voles and I bankvole
      were simultaneously infected by borreliae and leptospirae. B. garinii and
      Grippotyphosa serogroup leptospira were simultaneously isolated from 2 root
      voles, and B. garinii and Javanica serogroup Leptospira interrogans--from 1 root
      vole. A bank vole was infected by B. afzelii and Javanica serogroup leptospira.
      Mixed-infected animals composed 1.4% of all animals of background species studied
      in parallel. CONCLUSION: The data obtained indicate a presence of natural foci of
      leptospiroses in the southern taiga forest pre-Urals. The data confirm the
      conceptions regarding a predominant presence in European forest ecosystems of
      foci with Grippotyphosa serogroup L. interrogans pathogen, and the main carrier
      ofthese leptospirae being bank vole. Combined natural foci of spirochetoses of
      two groups (ixodes tick borrelioses and leptospiroses) were detected.

PMID- 22145346
TI  - [Detection of natural tularemia foci in Mongolia].
AB  - AIM: Study of the current spread of natural tularemia foci in Mongolia and its
      epizootic activity evaluation for consequent substantiation of the
      recommendations for prophylaxis of this disease. MATERIALS AND METHODS: Study of
      1119 pellet specimens from predatory birds obtained in 6 aimag in Mongolia in
      2008--2010 was performed. Tularemia antigen was detected by using antibody
      neutralization reaction (ANR) and passive hemagglutination reaction (PHR) with
      tularemia diagnosticums. Tularemia DNA was detected by PCR by using strain
      specific primers. Presence of plague antigen in PHR with plague immunoglobulin
      diagnosticum was also studied in all the samples. RESULTS: Epizootologic
      monitoring allowed the detection of natural tularemia foci in 5 of the 6 studied
      aimags in Mongolia. PHR was the most effective study method that allowed to
      detect tularemia antigen in the environmental objects in high quantities (up to
      9.2% of positive samples) and high titers (up to 1:1600). PCR was less effective.
      Plague antigen was detected in 9 samples in 2010 for the first time, and in 3
      cases together with tularemia antigen, which indicates a presence of combined
      natural foci of tularemia and plague in this territory. CONCLUSION: In the
      studied regions of Mongolia natural tularemia foci were detected, their epizootic
      activity was determined and recommendations for future study tactics of natural
      tularemia foci were given.

PMID- 22145347
TI  - [Detection of leptospirosis infection in certain wild and domestic animals in
      Mongolia].
AB  - AIM: Serological examination for leptospirosis of domestic and certain species of
      wild animals in Mongolia. MATERIALS AND METHODS: Collection of material from
      domestic and wild animals was performed in 2009--2010 in 7 aimags (regions) of
      Eastern, Central and Southern Mongolia. Serological study of filter paper dried
      blood samples obtained from 51 specimens of cattle and small cattle, camels, and
      545 specimens of rodents of various species was performed in microagglutination
      reaction (MAR) of leptospirae with 13 reference strains. RESULTS: There is a
      presence in certain regions of Mongolia of anthropurgic loci of leptospirosis
      infection including arid zones where ecological conditions do not favor the
      development of epizootic process. The results of the study indicate the epizootic
      significance of Tarassovi serogroup leptospirae in cattle and Sejroe serogroup
      (probably hardjo serovar) in goats, sheep and camels. Results of serological
      studies of desert and steppe specimens of wild fauna of Mongolia suggest a
      possibility of circulation of leptospirae in natural foci. CONCLUSION: Detection
      in a significant percent of cases in tarbagan and long tailed ground squirrel
      blood sera of agglutinins to Pomona (mozdok) leptospirae with negative MAR
      results for Pomona (pomona) strain suggests a presence of a pathogen of a
      previously unknown serovar. However final conclusion could be made only after the
      isolation of cultures of the pathogen and their identification.

PMID- 22145348
TI  - [Molecular-biological and antigenic features of H5N1 subtype highly pathogenic
      influenza virus strains isolated in southern Siberia in 2005-2009].
AB  - AIM: Study of molecular-biological and antigenic features of H5N1 subtype virus
      strains isolated in southern Siberia in 2005-2009. MATERIALS AND METHODS: Study
      was performed by using standard procedures according to WHO recommendations.
      RESULTS: Hemagglutinin gene of H5N1 subtype virus strain isolated in Siberia
      belongs to 2 genetical lineages: 2.2 and 2.3.2. Strains of these 2 lineages have
      antigenic differences. All of the strains are highly pathogenic for chicken and
      white mice. CONCLUSION: H5N1 subtype highly pathogenic influenza virus variants
      of 2 different antigenic lineages that have antigenic differences circulated in
      Siberia in 2005-2009. A possible role of antigenic drift in evolution of H5N1
      subtype influenza virus is discussed.

PMID- 22145349
TI  - [Comparative immunogenicity studies of cultural and peptide influenza vaccines].
AB  - AIM: Comparative immunogenicity studies of experimental vaccines based
      onA/Aichi/2/68 neuraminidase peptide fragments (NA) and influenza virus A and B
      strains produced in MDCK cell culture. MATERIALS AND METHODS: Anti-hemagglutinin
      and virus neutralizing activity of mice sera was determined in MN and HI
      reactions in accordance with the WHO recommendations. RESULTS: Sera against
      peptides 136-147 and 154-164 from variable sites, as well as against peptide 314
      328 from conservative region of the heavy chain of A/ Aichi/2/68 influenza virus
      NA showed distinct anti-hemagglutinin and neutralizing activity against
      homologous influenzavirus. Anti-(314-328) serum was also active in HI and MN
      reactions against other strains of the H3N2 subtype. Combined administration of
      peptide sample with an immunomodulator (Immunomax) increased the immunogenicity
      to the level of the cultural samples based on influenza A virus. CONCLUSION: The
      results show higher immunogenicity of cultural vaccines based on influenza virus
      in comparison to peptide samples. A possibility of peptide vaccine immunogenicity
      increase was demonstrated by combined administration with the immunomodulator.

PMID- 22145350
TI  - [Immunogenic properties and molecular-genetic features of native and inactivated
      Chlamydia trachomatis MT-2A serovariant D strain].
AB  - AIM. Study of antibody genesis after introduction of native and inactivated
      Chlamydia trachomatis MT-2A strain into Balb/c mice and analysis of molecular
      genetic features of omp A gene that is responsible for its immunogenicity.
      MATERIALS AND METHODS: Chlamydia infection was modeled in Balb/c mice by using
      human isolated C. trachomatis serovariant D. RESULTS: After the introduction of
      this strain, 5 days after the infection of mice A, M and G class antibodies
      including G class antibodies against chlamydia heat shock protein are induced.
      Studies of molecular-genetic features of the isolated C. trachomatis MT-2A strain
      showed presence of 2 nucleotide mutations in ompAgene. A synonymous substitution
      of cytosine to thymine in position 574 (CD) that does not result in amino acid
      substitution in the protein was registered. A non-synonymous substitution of
      thymine to guanine was present in position 843 (VDIII), that is most probably one
      of the main reasons of the registered higher immunogenicity of C. trachomatis MT
      2A serovariant D strain. CONCLUSION: Further studies of C. trachomatis MT-2A
      serovariant D strain are promising, but do not exclude search of other
      immunogenic strains for the generation of agents for specific prophylaxis and
      immunotherapy of chlamydiosis.

PMID- 22145351
TI  - [Multidirectional effect of MIF and sodium polyprenyl phosphate on the course of
      experimental flavivirus infection in mice].
AB  - AIM: Study of macrophage migration inhibiting factor (MIF) effect after
      intracerebral administration on the course of experimental infection induced in
      mice by tick borne encephalitis virus (TEV), and study of sodium polyprenyl
      phosphate (PPP) and/or antibodies against MIF on the course of this infection
      against the background of MIF administration. MATERIALS AND METHODS: Phosprenil
      preparation was used as a source of PPP. PPP was administered intracerebrally.
      MIF--human recombinant (R&D, USA), mice--Balb/c line. RESULTS: In the sera of
      mice infected with TEV, MIF production stimulation was detected at days 8 through
      10 after the infection--against the background of clinical signs presentation of
      tick borne encephalitis (TE). Administration of PPP to infected mice, on the
      contrary, resulted in MIF production suppression at the specified period. After
      administration of 20 ng of MIF to mice, lethality increased by 40% and average
      life span decreased by 2.3 days. Thus, MIF at high doses caused an increase of
      infection course severity, induced by TEV in mice, and administration of 60
      microg of PPP resulted in the protection from infection in 100% of cases.
      Intracerebral administrationto mice of antibodies against MIF resulted in a
      decrease of lethality indicator up to 26% as compared with control and an
      increase of averagelife span by 5.5 days. During simultaneous administration into
      the brain of infected mice of MIF, PPP and antibodies against MIF, prevention of
      MIF-induced increase of TE course severity was registered. CONCLUSION: The data
      obtained allow to conclude that MIF may serve as an indicator of TE course
      severity, and possible prognostic indicator of meningo-encephalitic form
      development in humans.

PMID- 22145352
TI  - [Development of Staphylococcus Haemolyticus multilocus sequencing scheme and its
      use for molecular-epidemiologic analysis of strains isolated in hospitals in
      Russian federation in 2009-2010].
AB  - AIM: Development of Staphylococcus haemolyticus strain typing method based on
      multilocus sequencing for resolving problems of molecular epidemiology. MATERIALS
      AND METHODS: 102 strains of coagulase negative staphylococci (CNS) isolated in
      hospitals of various specialization in N. Novgorod and Moscow were studied.
      Species identification of strain was performed by using tuf gene fragment
      sequencing, S. haemolyticus strain differentiation--by MLST results. eBURST
      approach was used for cluster analysis of MLST data; structural changes in
      tagatose-6-phosphate kinase were studied by using InterProScan platform and SWISS
      MODEL site programs; MLST scheme gene allele variability analysis was performed
      by using MEGA4.0 program package. RESULTS: In the 102 strains sampled CNS was
      detected in 28 strains of the S. haemolyticus species. The MLST scheme developed
      for the first time for S. haemolyticus including mvaK, rphE, tphK, gtr, arcC,
      triA, aroE genes allowed the differentiation of the sampled strains by 11
      genotypes. Strains with ST 3, 8, 6, 1, 4, 5 and 11 differed by highest
      epidemiologic significance. Cluster and phylogenetic analysis of the data
      obtained showed a high adaptive ability of the nosocomial S. haemolyticus
      strains. Multiresistance to antibacterial preparations was detected in the
      analyzed strains. CONCLUSION: The MLST method developed was effective in the
      differentiation of S. haemolyticus strains that circulate in hospitals and
      threaten both neonates and hospitalized adult patients.

PMID- 22145353
TI  - [Development of PCR test system based on colA gene for detection of leptospirae
      in clinical material].
AB  - AIM: Development of primers for the detection of leptospirae in clinical material
      including urine. MATERIALS AND METHODS: Study of specificity and sensitivity of
      primers complementary to colA gene in standard PCR by using DNA preparation of
      cultures of pathogenic and saprophytic leptospirae, biological materials from
      healthy humans and dogs, including contaminated with pathogenic leptospirae
      culture. RESULTS: Specific interaction of these primers with DNA of pathogenic
      leptospirae of 14 serogroups was established. Sensitivity of the technique was 50
      cells in 1 ml of sample. CONCLUSION: The primers described fulfill the
      requirements for the sensitivity and specificity and can be recommended for the
      detection of leptospirae in both serum and urine.

PMID- 22145354
TI  - [Features of intestine microbiocenosis and systemic inflammation factors in
      chronic heart failure patients].
AB  - AIM: Intestine microbiocenosis structure, endotoxinemia level, C-reactive protein
      (CRP) and TNFalpha concentration in chronic heart failure patients (CHF) were
      studied depending on disease severity. MATERIALS AND METHODS: Clinical,
      echocardiographic and laboratory examination of 104 patients was performed: 75
      CHF patients and 29 healthy volunteers. Laboratory examination included
      bacteriologic analysis of feces for dysbiosis, determination of endotoxin (ET)
      levels, CRP and TNFalpha levels in blood serum. RESULTS: More expressed
      alterations in large intestine microbiocenosis and an increase of endotoxinemia
      and systemic inflammation factors (TNFalpha and CRP) levels were detected in
      patients with CHF in comparison to individuals without circulatory system
      pathology. CHF progression is associated with an increase of intestine dysbiosis,
      and ET, TNFalpha and CRP levels in blood. CONCLUSION: Endotoxinemia in CHF
      patients, that is caused by an increase in intestine wall permeability during
      development of venous congestion in systemic circulation, results in immune
      system activation manifesting in an increase of systemic inflammation factor
      level in blood that can aggravate the CHF course.

PMID- 22145355
TI  - [Clinical effect of chitosan in bacterial vaginosis therapy].
AB  - AIM: Determination of antibacterial activity of acid-soluble chitosan in
      bacterial vaginosis therapy in women of reproductive age and comparison of
      therapy results of traditional scheme and local administration of acid-soluble
      chitosan. MATERIALS AND METHODS: Vaginal microflora of 76 gynecologic and
      obstetrical female patients (18-43 years of age) with bacterial vaginosis
      diagnosis was examined by using bacteriological method. Control group consisted
      of 30 practically healthy women. Sensitivity of 145 bacteria strains from 14
      genera to 2% acid-soluble chitosan solution (200-250 kDa molecularweight) was
      determined by using agar diffusion method. RESULTS: During bacterial vaginosis
      members of the Gardnerella, Mobiluncus and Bacteroides genera dominated with a
      background reduction of lactobacilli quantity. An increase of population level of
      Staphylococcus, Enterococcus, Prevotella, Porphyromonas, Peptostreptococcus
      genera members, and Candida species was also observed. All the microorganisms
      were sensitive to 2% chitosan solution. Mycoplasma and Ureaplasma spp. were
      sensitive to chitosan in 82% of cases. Administration of chitosan in local
      therapy of vaginosis resulted in suppression of opportunistic microflora and
      clinical effect with a lack of adverse effects. CONCLUSION: Local administration
      of chitosan is perspective against bacterial vaginosis.

PMID- 22145356
TI  - [Efficacy of combined administration of ridostin and oseltamivir (tamiflu) for
      therapy and prophylaxis of experimental infection induced by influenza virus A
      (H5N1) in mice].
AB  - AIM: Study of possibility of treatment-prophylaxis effect increase during
      combined administration of ridostin and tamiflu in experiments in mice infected
      with highly pathogenic influenza virus strain A/chicken/Kurgan/05/2005 (H5N1).
      MATERIALS AND METHODS: Balb/c line mice infected intranasally with influenza
      virus at 100 and 10 LD50 doses received ridostin and tamiflu as monopreparation
      or the combined variant before or after the infection. The mice were observed for
      16 days, lethality rate, protection coefficient and average life span were
      evaluated. Virus concentration in lungs was determined by using titration in MDCK
      cell line. RESULTS: Combined administration ofridostin and tamiflu after the
      infection increased survivability of the animals when compared with the control
      group, and reduced influenza virus concentration in lungs. CONCLUSION: Treatment
      effect during combined administration of ridostin and tamiflu after influenza
      virus infection increased.

PMID- 22145357
TI  - [Role of several periodontopathogenic microorganisms and tlr4 gene Asp299Gly
      polymorphism in atherosclerosis pathogenesis].
AB  - AIM: Establishment of presence of periodonto-pathogenic microorganisms in
      atherosclerosis plaque and surrounding tissues, and possible relation of
      development of atherosclerosis and TLR4 gene Asp299Gly polymorphism in ischemic
      heart disease patients (IHD). MATERIALS AND METHODS: Samples of coronary vessels
      obtained during autopsy of 31 individuals deceased from IHD and 5 individuals
      deceased due to reasons not related with IHD were studied. PCR was used to
      determine DNA of the microorganisms. TLR4 gene polymorphic segment was amplified
      by using specific primers. RESULTS: Analysis of coronary vessel atherosclerotic
      plaques revealed presence of the studied periodontopathogenic microorganisms in
      83.9% of cases. The most frequently detected were Porphyromonas gingivalis
      (64.5%), Treponema denticola (41.9%), Actinobacillus actinomycetemcomitans
      (32.3%), less frequently--Bacteroides forsythus and Prevotella intermedia (12.9%
      and 6.5% respectively). In 51.6% of cases 2 or more microorganisms were detected.
      Only in 11.1% ofcoronary artery samples, with plaques containing microorganisms,
      the microorganisms were detected in undamaged tissues. Patients deceased from IHD
      had TLR4 gene 299Gly allele significantly more frequently. CONCLUSION: The
      studied periodontopathogenic microorganisms can play an important role in the
      pathogenesis of atherosclerotic injury of coronary arteries in IHD. The presence
      of TLR4 gene allele 299Gly significantly contributes to these processes.

PMID- 22145358
TI  - [Laboratory diagnostics of HIV infection in Syberian federal district].
AB  - Spread of HIV infection in the Russian Federation is an important problem of the
      state healthcare. Data on HIV infection diagnostics in the Syberian federal
      district in 2005-2009 are presented. Coverage of population by HIV examination,
      rate of positive study results by enzyme immunoassay and rate of positive EIA
      confirmed by immunoblotting are presented.

PMID- 22145359
TI  - [Results of sociological studies of HIV/AIDS problem in convicts serving the
      sentence in Yamalo-Nenets autonomous area].

PMID- 22145360
TI  - [Biodiversity and evolution of circulating bacteria and virus populations. Novel
      problems of medical microbiology].
AB  - Biodiversity and evolution of circulating bacteria and virus populations is a
      serious scientific problem, solving this problem is necessary for effective
      prophylaxis of infectious diseases. Principal trends of development in this field
      of science are described. Results of studies that were carried out and
      investigated biodiversity of principal pathogens in Russia and St. Petersburg in
      particular are presented. Risk of infectious security of society caused by
      increasing diversity of pathogenic microorganisms is described, and priority
      trends of research development in this field are specified.

PMID- 22145361
TI  - [New innate immunity receptor agonists from sea hydrobionts].
AB  - Scientific data and data obtained by us regarding new innate immunity receptor
      agonists from sea hydrobionts are presented. Highly efficient and low toxic
      biologically active substances isolated from sea organisms are inductors of
      dendritic cells maturation, activate neutrophils, monocytes/macrophages and NK
      cells, have an anticomplementary (fucoidans) and pro- and anti-inflammatory
      effects. Protective properties of biologically active substances are exhibited
      when various pathogens entering the organism--bacteria, viruses, protozoa, fungi.
      These substances may become a basis for the creation of new pharmaceutical
      preparations.

PMID- 22145362
TI  - [Genetical features of influenza virus A (H1N1) strain that caused the 2009
      pandemic].
AB  - Genetical features of the A(H1N1) influenza virus strain that caused the 2009
      pandemic are analyzed in the review. Mutations typical for this strain, unique
      and similar to influenza viruses of swine, avian and seasonal types, and
      phenotypic (pathologic) features associated with them, that are experimentally
      confirmed, are described. A possibility of reassortation of avian and swine
      influenza viruses and possible epidemiologic consequences are discussed.

PMID- 22145363
TI  - [Actual problems of vaccinoprophylaxis management in Russian federation].

PMID- 22145364
TI  - ["Fingerprints" of malaria parasites in human genome].
AB  - The effect of malaria epidemics on human genome alteration is discussed. Global
      and regional features of human polymorphism are examined through the genetic
      selection lens implemented by different malaria parasites species over the course
      of Homo sapiens evolution.

PMID- 22145365
TI  - [Terminologic aspects of infections associated with administration of medical
      aid].
AB  - Evolution of key terms used in epidemiology of nosocomial infections is
      discussed. A modern point of view on terminology and comparison of Russian terms
      with foreign analogues are presented.

PMID- 22145366
TI  - [Genetic safety of cellular therapy].
AB  - This paper presents the main results of the study on chromosome and genome
      variability of mesenchymal stem cell cultures from bone marrow and adipose tissue
      carried out in the Laboratory of Mutagenesis, Research Centre for Medical
      Genetics, over the last three years. Genome stability was assessed from DNA
      damage using the DNA comet assay, karyotyping and registration of aneuploidy by
      the FISH method. We found that DNA damage rate in MSC cultures from bone marrow
      was 3.9% and 3.8% at the early (2-5) passages and the late (10-15) passages
      respectively. The cultures were characterized by high dispersion of individual
      values. Karyotyping showed mosaicism in both types of MSC cultures at the early
      and late stages of cultivation. The fraction of abnormal cells in some cultures
      amounted to 80-90%. Evaluation of aneuploidy in interphase cells revealed 1.34%
      of aneuploid cells (on the average) per one "conventional" chromosome; their
      overall frequency in the genome amounted to 20-40%. The frequency of aneuploid
      cells was similar at the early and late passages. Cultures with clones of
      trisomic and monosomic cells were revealed. The probability of occurrence of
      abnormal cells may increase by virtue of de novo mutations in the culture and as
      a result of positive selection of the cells existing in the organism that exhibit
      a higher reproduction rate in culture. Based on the experimental data on
      mutational process, selection of mutant cells and clone formation, it is
      concluded that cytogenetic control of stem cells is necessary to ensure the
      safety of cellular therapy.

PMID- 22145367
TI  - [Organization of medical genetic service in Russia].
AB  - Short history of the development of medical genetic service in Russia from the
      1960s till now is described. Analysis of many orders of the Ministry of Health of
      USSR and Russia was performed which shows how separate components of the service
      were designed and integrated into the efficacious genetic counseling system. All
      of them were supported by educational programs. The important contribution made
      by professor Nikolai Bochkov to the creation of genetic service in Russia
      especially at the early stages is underlined.

PMID- 22145368
TI  - [Phenome-genome relations and pathogenetics of multifactorial diseases].
AB  - This study of phenome-genome relations in multifactorial diseases is focused on
      the principal notions and concepts, such as "arthritism", syntropies and
      syntropic gene, diseasome, orthologic phenotypes (phenologs). The results of
      original investigations into synthropic genes responsible for predisposition to
      multifactorial diseases are presented along with analysis of DNA methylation in
      atherosclerotic plaques and whole-genome analysis of asthma. A hypothesis is
      proposed that ischaemic preconditioning may be a mechanism underlying the stable
      cardiovascular disease continuum as a special form of synthropy. Two principal
      lines of research on genetics of multifactorial disease are distinguished, viz.
      ontogenesis of multifactorial diseases and epigenetic inheritance.

PMID- 22145369
TI  - [Personalized medicine: expectations, disappointments and hopes].
AB  - Impressive advances in the studies of human genome, identification of mutant
      genes of hereditary diseases and candidate genes of many chronic multifactorial
      diseases (MFD) laid the foundation of molecular medicine. Its characteristic
      features, such as the focus on individual prophylactic care, give reason to
      consider it as personalized predictive medicine (PPM). The fundamental concept
      behind PPM comprises the notion of genetic passport and its methodological basis
      is genetic testing (GT). Recent progress in PPM has been achieved due to the
      introduction of comprehensive genomic screening of associations. At the same
      time, the contribution of known individual genes to the development of MFD
      appears to be relatively insignificant which does not allow to identify the main
      causes of MFD. It gave rise to some scepsis as regards the value of genome as a
      source of information for practical medicine. Possibilities for the improvement
      of GT and conditions for the introduction of the available data into clinical
      practice are discussed. The necessity to attract clinicians to the work on PPM is
      emphasized. The development of unified MFD gene panels for clinical application
      and software for the evaluation and interpretation of GT results for doctors and
      patients is an indispensable condition for the use of PPM knowledge in the
      healthcare practice. The importance of solution of relevant ethical, juridical,
      and social issues is underscored.

PMID- 22145370
TI  - [Genetic toxicology].
AB  - Problems and achievements in genotoxicology are briefly discussed with special
      reference to genotoxicologic assays, genotoxicologic risks, modification of
      genotoxicologic effects, and individual sensitivity to genotoxic agents. The
      basic terms and concepts of genetic toxicology as well as the main lines of its
      further development are considered.

PMID- 22145371
TI  - [HFE gene polymorphism in the population of Northern Asia].
AB  - Human HFE gene haplotype analysis with reference to IVS2(+4)t/c, IVS4(-44)t/c,
      IVS5(-47)a/g polymorphic sites was performed in different North Asian ethnic
      groups. Of the eight possible intronic haplotypes, TTG, TTA, CTA and CCA were
      identified. High frequency of the CCA haplotype appears to be a characteristic
      feature of all Asian native populations. Potential functional importance of IVS4(
      44)t/c polymorphism is demonstrated. Patients presenting with iron overload
      syndrome are shown to have low frequency of IVS4(-44)c.

PMID- 22145372
TI  - [Chromosome territories in the interphase nucleus in normal or pathological
      condition].
AB  - The non-random arrangement of chromosomes in the interphase nucleus was observed
      for the first time in the late XIX century. However, considerable progress in
      studying chromosome territories became possible only in the end of the XX century
      mainly due to advances in microscopy and molecular biology. At present,
      chromosome territories are believed to play an important role in epigenetic
      regulation of genome activity during various cell processes including but not
      limited to cell cycle, differentiation, stress response. 3D structure of genome
      also plays an important role in pathogenesis of various hereditary diseases and
      cancer. This article describes main provisions of the chromosome territory theory
      and current trends toward further development of human genetics based on the new
      knowledge about the role of chromosome territories.

PMID- 22145373
TI  - [VEGF gene expression in transfected human multipotent stromal cells].
AB  - Dynamics of VEGF gene expression in transfected multipotent stromal cells from
      adipose tissue was examined using electroporation and lipofection. Differences in
      the potency and dynamics of plasmid elimination (up to day 9) between cell
      cultures were observed. All cultures were divided into fast and slow plasmid
      eliminating ones. Interculture differences in VEGF expression were detected. The
      possibility of a 5-6-fold increase of VEGF expression was shown. There were no
      differences in transfection potency, plasmid elimination dynamics, and VEGF
      expression after transfection by both nonviral methods.

PMID- 22145374
TI  - [Analysis of DNA and chromosome damage by the methods of molecular cytogenetics].
AB  - The main hybrid techniques of molecular cytogenetics are described.
      Methodological aspects of combination of fluorescence in situ hybridization
      (FISH) with the comet assay and micronuclei (MN) test are discussed along with
      results of their application to evaluate and locate DNA and chromosome damage in
      the genome. The experience of the authors with the application of FISH in
      combination with the comet assay and MN test are reported.

PMID- 22145375
TI  - [Somatic chromosome mutagenesis in residents of Ukraine exposed to ionizing
      radiation in different periods after the Chernobyl accident].
AB  - The authors summarize results of 25-year selective cytogenetic monitoring of the
      priority groups in different periods after the Chernobyl accident. The increase
      in intensity of somatic chromosome mutagenesis in exposed individuals as a result
      of both targeted and non-targeted radiation-induced cytogenetic effects has been
      confirmed including delayed, transmissible, hidden chromosome instability and the
      bystander effect.

PMID- 22145376
TI  - [Ethical problems of mutagenesis and genetic testing at the workplace].
AB  - Selected ethical problems arising in the studies of mutagenic effects and genetic
      testing at the workplace (genetic monitoring and genetic screening) are
      discussed.

PMID- 22145377
TI  - [Estimation of genetic safety of nanomaterials].
AB  - Problems pertaining to the estimation of genetic safety of nanomaterials are
      considered. Comparative analysis of current approaches to testing mutagenicity in
      this country and abroad is presented. The necessity of mandatory evaluation of
      genotoxic and mutagenic properties of modern nanomaterials in accordance with
      international standards is substantiated. The system of the existing methods for
      the purpose should be supplemented by new scientifically sound and verified
      techniques. Methodological peculiarities of the assessment of organ-specific
      nanomaterials are described. It is recommended to correct certain provisions of
      the approved Guidelines 1.2.2520-09 concerning mutagenic properties of
      nanomaterials.

PMID- 22145378
TI  - [Organization of genetic service in multiprofile hospitals].
AB  - The necessity to organize genetic service for patients and their relatives in
      multiprofile hospitals is discussed. Analysis of long-term experience of the
      Medical Genetic Department at the First Moscow Medical University yielded main
      characteristics to be used for the organization of medical genetic service at
      such hospitals based at independent divisions. Such services ensure more
      efficacious care than those at the regional level.

PMID- 22145379
TI  - [Aneugenic effect of ionizing radiation: a new component in the estimation of
      genotoxic risks].
AB  - Assessment of genetic risks related to effects of ionizing radiation on the human
      body remains a topical problem in medical genetics. Along with numerous data
      about the influence of radiation on chromosomes of man and model organisms, there
      are some facts suggesting possible aneugenic effect in addition to the well-known
      clastogenic influence generally recognized as a marker for biological dosimetry.
      The interest in genetic risks of aneuploidy is in the first place due to its
      gross mutagenic potential. Simultaneous changes in a large number of gene copies
      are regarded as an important contributing factor of malignant cell transformation
      and tumour growth. The role of aneuploidy in aging and multifactorial diseases is
      discussed and some data suggesting aneugenic effect of ionizing radiation are
      presented. The potential significance of aneuploidy for risk assessment of
      mutagenic factors is considered.

PMID- 22145380
TI  - [Increased arterial stiffness is a significant but not obligatory factor of
      arterial hypertension in persons over 60 years of age].
AB  - AIM: To ascertain whether high arterial rigidity is obligatory in arterial
      hypertension (AH) and the presence of AH is obligatory in patients with rigid
      arteries. MATERIAL AND METHODS: Volume sphygmography (VS) was made in 153
      patients aged 60-86 years: 96 patients with untreated AH of degree 1-3 (40 males
      aged 71.0 +/- 7.6 years) and 57 normotensive subjects without cardiovascular
      symptoms (31 males aged 66.6 +/- 6.2 years). VS measured ankle-shoulder velocity
      of the pulse wave (PWVas) and cardiac-ankle vascular index (CAVI). PWVas > M+STD
      and CAVI > M+2STD (STD is deviation from mean value) were considered above normal
      for the age. RESULTS: Hypertensive patients had significantly higher arterial
      rigidity than normotensives (PWVas 178 +/- 3.0 and 15.6 +/- 2.3 m/s,
      respectively, p = 0.00001); CAVI--9.7 +/- 2.1 and 8.6 +/- 1.1, respectively, p =
      0.0003). Arterial rigidity in hypertensive patients occurred significantly more
      frequently than in normotensive subjects: by PWVas in 46 and 25% cases (p =
      0.01), by CAVI--in 41 and 5% cases (p < 0.0001), respectively. It is essential
      that arterial rigidity was not increased in 54% hypertensive patients by PWVas
      and in 75% by CAVI. CONCLUSION: PWVas and CAVI were higher in elderly
      hypertensives than in elderly normotensives but elevated arterial rigidity was
      not obligatory in hypertensives while 25% elderly normotensives had it. Thus,
      elevated arterial rigidity is an essential but not obligatory mechanism of AH
      development in the elderly.

PMID- 22145381
TI  - [The extent of coronary stenosis and the level of antibodies to atherogenic
      lipoproteins in patients with coronary heart disease].
AB  - AIM: To study association between the level of antibodies to oxidized low-density
      lipoproteins (anti-OLDL) and the extent of coronary stenosis (CS) in patients
      with coronary heart disease (CHD). MATERIAL AND METHODS: Sixty CHD patients were
      examined for titer of anti-OLDL, levels of total cholesterol (TC), LDLP
      cholesterol, HDLP cholesterol, triglycerides. Selective coronarography (SC) was
      made on demand. RESULTS: Elevated titer of anti-OLDL was found only in 12
      examinees. It was significantly lower in CHD women than in men. No significant
      differences by anti-OLDL were found in CHD patients with and without significant
      risk factors. SC registered in all CHD examinees local stenosis of different
      severity. Stenosis in 3 coronary arteries was detected in 31 cases, in 2 coronary
      arteries--in 14, in 1 coronary artery--in 15 patients, most frequently the
      affection was located in the diagonal branch of the left coronary artery.
      Stenosis of the left coronary artery trunk was diagnosed in one case. The
      correlation analysis revealed a strongly significant positive correlation between
      content of anti-OLDL and the degree of CS. CONCLUSION: The level of anti-OLDL in
      CHD patients directly correlates with the degree of CS and is a marker of
      coronary atherosclerosis severity.

PMID- 22145382
TI  - [Cardioprotective characteristics of the drug nicorandil in patients with
      coronary heart disease].
AB  - Nicorandil, opener of potassium channels, was studied in Russia and abroad. Its
      cardioprotective, anti-ischemic, pharmacokinetic and pharmacodynamic properties
      are reviewed as well as side effects and area of application in patients with
      stable coronary heart disease (CHD). The trial have found efficacy of nicorandil
      in prevention of anginal attacks. Also, the drug increases exercise tolerance.
      Administration of nicorandil is indicated before intervention on coronary
      arteries for reproduction of the effect of myocardial preconditioning. Nicorandil
      is recommended for treatment of patients with chronic stable coronary heart
      disease.

PMID- 22145383
TI  - [Early invasive and non-invasive approach to treatment of acute non-ST-segment
      elevation coronary syndrome].
AB  - AIM: The aim of the study is to assess the efficiency of early invasive treatment
      versus conservative treatment for patients with non-ST acute coronary syndrome
      (ACS), and to study immediate results of percutaneous coronary intervention (PCI)
      in terms of the risk of adverse events. MATERIAL AND METHODS: The investigation
      includes 112 patients with non-ST ACS having risk of adverse outcome determined
      by the GRACE system. More than half of the patients (77/68.8%) underwent
      diagnostic coronary angiography within 72 hours of admission, and the decision
      was made on a subsequent treatment strategy (early invasive or conservative
      approach). In-hospital outcomes (cardiac deaths, nonfatal MI, reMI), cumulative
      frequency of these events have been studied according to the risk assessment
      scale GRACE and treatment strategy. RESULTS: Low risk was determined in 33.9% of
      patients, intermediate--in 32.1%, and high--in 33.9%. On the whole, frequency of
      myocardial revascularization was assessed as 56.3%. Fifty-one (45.5%) patients
      received early invasive treatment, 12 (10.7%)--coronary artery bypass grafting
      (CABG). A conservative approach was used in 49 cases (43.8%). An early invasive
      treatment was given to 20 patients (52.6%) from each of the low- and high-risk
      groups, 11 (30.6%)--from the intermediate risk group. In-hospital cardiac deaths
      were observed only in the high-risk group, and this number was higher in case of
      conservative treatment versus early invasive treatment: 3 (30%) versus 1 (50%).
      Non-fatal MIs in the form of re(MI) were also diagnosed only in the high-risk
      group following conservative treatment: 2 (20.0%). Nevertheless, no reliable
      difference in the frequency of each complication was found (p = 0.095; p = 0.1).
      Significant differences in the high-risk group were proven while comparing the
      impact of early invasive and conservative approaches on the cumulative frequency
      of in-hospital death and (re)MI cases (50.0% versus 5.0%; p = 0.009). No benefits
      of an early invasive approach were identified for low-risk and intermediate risk
      groups. CONCLUSION: Early invasive approach compared with a conservative approach
      in high risk patients with non-ST acute coronary syndrome can improve clinical
      outcomes with a decrease in the total frequency of in-hospital death, reMI.

PMID- 22145384
TI  - [Long-term prognosis in patients with acute non-ST-segment elevation myocardial
      infarction depending on dynamics of tissue myocardial dopplerography].
AB  - AIM: To study long-term prognosis in patients with non-ST elevation acute
      myocardial infarction (AMI) with reference to changes in myocardial tissue
      dopplerography (MTD) in the course of treatment. MATERIAL AND METHODS: MTD
      echocardiography was conducted in 88 non-ST elevation AMI (mean age 58.0-9.8
      years) and 34 healthy volunteers (mean age 58.0 +/- 9.8 years). Measurements were
      made of the velocity of systolic, early and late diastolic peaks at 4 levels of
      interventricular septum, anterior, lateral and inferior walls of the left
      ventricle (LV). MTD was repeated before the discharge from hospital. The patients
      were followed up for 10-18 months after the discharge. RESULTS: By MTD results
      the patients were divided into 3 subgroups: 1--an asymmetric decrease of MTD
      values--17(19.3%) patients who had a 20% reduction of the systolic and early
      diastolic peak velocity compared to healthy controls on one or two adjacent LV
      walls; subgroup 2--a diffuse decline of MTD values--61 (69.3%) patients. Their
      velocity of systolic and early diastolic peaks was subnormal on all the walls,
      all levels of estimation; subgroup 3--10 (11.4%) patients without MTD changes.
      These proportions changed in the course of treatment: the number of patients with
      a diffuse decrease of MTD values reduced to 31 (35.3%), the number of patients
      with an asymmetric MTD decrease rose to 37 (42%), and with unchanged MTD rose to
      20 (22.7%) patients. The rate of development of congestive cardiac failure (CCF)
      and asymptomatic LV dysfunction in the long-term period was significantly higher
      in the subgroup with retained diffuse decrease of MTD values. CONCLUSION: The
      treatment of non-ST elevation AMI reduces the number of patients with a diffuse
      decrease of MTD values and elevates the number of patients with asymmetric
      decrease of MTD and unchanged MTD. Persistence of MTD diffuse changes is an
      unfavourable prognostic factor in relation to CCF and LV silent dysfunction.

PMID- 22145385
TI  - [Relationship between concentration of lipoprotein-associated secretory
      phospholipase A2 and markers of subclinical atherosclerotic lesion of the
      arterial wall in patients with low and moderate risk by SCORE scale].
AB  - AIM To show relations between a concentration of lipoprotein-associated secretory
      phospholipase A2 (LPPLa2) and markers of subclinical atherosclerotic lesion of
      the arterial wall in patients with low and moderate risk by the SCORE scale.
      MATERIAL AND METHODS: A total of 378 individuals with low and moderate risk of
      atherosclerotic lesion of the arterial wall (285 females, 93 males) were divided
      into groups by (1) age and sex, (2) number of atherosclerotic plaques (ASP) in
      the carotid arteries: OASP (n=158), ASP (n=61), more than one ASP (n=159); (3)
      plaque characteristics: homogeneous (n=31), heterogenous (n=189), (4) the
      presence of ASP in CA and level of LPPLa2 in the blood (with high content--n=137,
      with normal content--n=83). Duplex CA scanning was made to estimate intima-media
      thickness (IMT), to detect AP in the CA. Computer sphygmography estimated
      velocity of the pulse wave (PWV) from the carotid to femoral artery. Normal
      values of IMT and PWV were estimated individually with reference to gender and
      age. LPPLa2 was measured immunoturbodimetrically using diagnostic kits (PLAC Test
      Elisa Kit, dia Dexus, U.S.A.), shreshold value < 200 ng/ml. RESULTS: LPPLa2
      content medians in different age groups in males and females differed
      insignificantly. LPPLa2 concentration in the groups of patients regarding ASP in
      CA was elevated in relation to the threshold value (200 ng/ml) in all the groups
      but did not significantly differ: 216 (179-257) ng/ml in the group OASP, 226 (190
      274) ng/ml--in the group of patients 1ASP and 212 (174-254) ng/ml--in the group
      of patients more than one ASP (p > 0.05). In the groups with homogeneous and
      heterogenous ASP significant differencies were neither between the medians nor
      between frequency of deviation from normal (p = 0.28). 25.5% patients from the
      group with an elevated level of LPPLa2 had ASP with a hypoechogenic component.
      CONCLUSION: No significant correlation was revealed between concentration of
      LPPLa2, IMT PWV, number of ASP and carotid stenosis.

PMID- 22145386
TI  - [Pharmacological protection of the myocardium with reamberin in coronary artery
      bypass grafting in patients with postinfarction angina].
AB  - AIM: To assess efficacy of reamberin in preoperative preparation and after
      coronary bypass (CB) in patients with macrofocal myocardial infarction (MI)
      complicated with postinfarction angina. MATERIAL AND METHODS: A total of 45
      patients with Q-positive MI complicated with postinfarction angina pectoris
      entered the trial. The study group consisted of 20 (44.4%) patients given 200-400
      ml injections of 1.5% reamberin solution for 3 days before coronary artery bypass
      grafting (CABG) and 3-5 days after it. The control group consisted of 25 (55.6%)
      patients given basic therapy without cardioprotection. ECTG-60, echocardiography,
      CM-ECG, laboratory tests were made before CABG. CABG was made in conditions of
      artificial blood circulation in all the patients. RESULTS: Clinical stabilization
      was observed after direct myocardial revascularization in hospitalized 25 (100%)
      patients of the study group and 22 (88%) patients of the control group. Early
      postoperative acute cardiac failure (ACF) developed in 3 (12%) patients from the
      study group and 9 (36%) from the control group (p = 0.04), arrhythmia occurred in
      2(8%) and 8(32%) patients, respectively (p = 0.03). Two (8%) control patients
      died in early postoperative period from acute cardiac failure. Perioperative MI
      occurred in 2(8%) control patients. After 12 months of the follow-up, patients of
      the study group had no recurrent angina pectoris, while among the controls 4(16%)
      patients had recurrent angina of FC III. After surgical intervention at discharge
      and 12 months after treatment patients of both groups improved systolic and
      diastolic functions of the left ventricle. Normalization of the diastolic
      function was registered in 80% patients of the study group (p < 0.001) and in 44%
      from the control group (p < 0.001) after 1 year follow-up. CONCLUSION: Reamberin
      reduces the number of postoperative complications, ischemic damage to the
      myocardium, significantly improves systolic and diastolic functions of the left
      ventricle.

PMID- 22145387
TI  - [Dilated cardiomyopathy as clinical syndrome: experience with nosological
      diagnostics with biopsy and treatment approaches].
AB  - AIM: To study possibility of nosological diagnosis in patients with dilated
      cardiomyopathy (DCMP) with use of myocardial biopsy. MATERIAL AND METHODS: The
      trial enrolled 62 patients (23 females) with DCMP syndrome (end diastolic left
      ventricular size > 5.5 cm, ejection fraction < 55%). Mean age of the patients was
      46.0 +/- 12.8 years. The examination included diagnosis of viral infections
      (Herpes virus, parvovirus B19), measurement of anticardial antibodies titer, 99Tc
      MIBI single photon emission computed tomography of the myocardium, multislice
      computed tomography, MRT of the heart, coronarography, morphological study of the
      myocardium (n=20) with application of polymerase chain reaction (PCR) for
      H.simplex viruses of types 1, 2 and 6, herpes zoster, Epstein-Barr,
      cytomegalovirus, parvovirus B-19, adenoviruses. The control group (20 operated
      patients with valvular heart disease and coronary heart disease) was examined for
      viral genome in the blood and myocardium. RESULTS: Complex examination of DCMP
      patients showed the following distribution by nosological entuities: myocarditis
      (n=41, 66.1%) including virus-positive (n=14), primary DCMP (n=16, 25.9%)
      including with non-compact myocarditis (NCM) in 3, with debute at delivery of the
      child--in 3. Arrhythmogenic right ventricular dysplasia combined with viral
      myocarditis (n=2), genetic myopathy (n=1) and Takayasu disease (n=1) combined
      with NCM, isolated NCM (n=1) were diagnosed in the rest cases. Morphological
      investigation of the myocardium was made in 20 patients: diagnosis of myocarditis
      and primary DCMP were made in 70% (including in 2 patients with CHD) and 20%.
      Detection of viral genome was 20 and 15% in the study and control group,
      respectively, in the myocardium--in 57.9 (test for parvovirus B19 was not made in
      26%) and 65.0% (complete diagnosis). All the virus-positive patients with DCMP
      were diagnosed to have signs of active/borderline myocarditis. Diagnostic
      criteria and poor prognosis factors were defined. CONCLUSION: The nosological
      diagnosis of DCMP was made in all the examinees basing on the complex of
      clinical, case history and device evidence. The diagnosis was morphologically
      verified in 33.9% patients. Treatment approaches are developed.

PMID- 22145390
TI  - [Chronic cardiac failure in the XXI century].
AB  - Wide clinical application of modern prophylactic, diagnostic and therapeutic
      methods has significantly improved clinical outcomes of cardiovascular disorders.
      However, much progress is not seen in survival of patients with chronic cardiac
      failure (CCF). Three possible causes of this situation are analysed: absence of
      evidence base in the treatment of CCF patients free of systolic dysfunction,
      difficulties in management of patients with end-stage CCF, need in new markers of
      CCF. Approaches to solution of these problems and CCF treatment optimization in
      general are discussed.

PMID- 22145388
TI  - [Pandemic influenza in Russia: specific features of clinical course and the
      absence of early etiotropic therapy as a risk factor of severe forms of the
      disease].
AB  - AIM: To assess efficacy and safety of ingavirin in the treatment of the flu
      caused by pandemic virus of flu A (H1N1) sw1 in hospitalized patients compared
      with oseltamivir. MATERIAL AND METHODS: A population-based comparative
      multicenter trial included 194 patients with verified diagnosis of the flu aged
      18-60 years with marked clinical symptoms, body temperature over 38 degrees C and
      duration of the disease 48 hours maximum. The patients were randomized into 2
      groups: group 1 (n=152) received ingavirin (90 mg once a day), group 2 received
      oseltamivir (n=42) in a dose 150 mg twice a day. Duration of the course was 5
      days. RESULTS: Ingavirin and oseltamivir normalized body temperature within
      treatment hours 24-36 if therapy was initiated in the first disease hours 27.0 +/
      10.0 and 31.9 +/- 10.4. Mean duration of the fever for ingavirin was 35.1 +/-
      14.5 hours, for oseltamivir--26.3 +/- 13.0 hours (p < 0.817). The antiviral
      medicines significantly reduced duration of intoxication (head ache, weakness),
      catarrhal symptoms (cough, tracheitis, rhinitis), rate of complication vs.
      patients untreated with antivirus drugs (n=30). CONCLUSION: The results of the
      treatment show safety and efficacy of ingavirin in uncomplicated flu caused by
      pandemic virus of flu A (H1N1) sw1 in inpatients. Early etiotropic therapy is a
      basic treatment policy able to reduce the number of severe complications and
      lethality.

PMID- 22145389
TI  - [Multicenter trial of olmesartan. Main results].
AB  - Development and introduction into practice of medicines reducing activity of the
      renin-angiotensin-aldosteron system the key element of which is angiotensin II
      (ATII) resulted in a significant improvement of efficacy of cardiovascular
      diseases treatment. Angiotensin converting enzyme (ACE) inhibitors and ATII
      receptor blockers (BRA II) effectively reduce arterial pressure, have a
      nephroprotective action in patients with diabetes mellitus, inhibit development
      of left ventricular hypertrophy. Unlike ACE inhibitors, BRA II do not exhibit the
      phenomenon of ATII concentration escape, they completely depress ATII interaction
      with AT1-receptors while AT2-receptors keep their ability to interact with this
      hormone. High probability of target arterial pressure achievement in the
      treatment with BRA II encourage higher compliance of the patients. The review of
      multicenter trials performed in 2007-2010 concerns a new BRA II representative-
      olmesartan medoxomil (OM). The trials run in two directions: hypotensive activity
      of OM and vaso- and other organ-protective OM properties.

PMID- 22145391
TI  - [Acute coronary syndrome in patients with type 2 diabetes mellitus].
AB  - According to evidence obtained from large epidemiological studies, an incidence
      rate of acute coronary syndrome (ACS) in diabetics is 2-3 times higher than in
      general population. Relevant invalidity and mortality is much higher than in
      patients free of diabetes. In type 2 diabetes mellitus a high risk of an
      unfavourable course and outcome of myocardial infarction was registered both
      within 30 postinfarction days and 1-3 years of follow-up. Poor prognosis persists
      despite adequate and early treatment. The results of the attempts to correct MI
      prognosis in diabetics by means of carbohydrate metabolism correction
      (multicenter trials DIGAMI-1, DIGAMI-2) are reviewed.

PMID- 22145392
TI  - [Statins in primary prophylaxis of cardiovascular diseases].
AB  - The review summarises data on statins efficacy in primary prophylaxis of
      cardiovascular complications. Main results of the JUPITER (Justification for the
      Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)
      trial are analysed in detail. Its role in possible changes in current
      recommendations on prophylaxis and treatment of atherosclerosis is shown. Statins
      are considered as drugs essential in the strategy of improvement of life quality.

PMID- 22145393
TI  - [From classification medicine to clinical medicine (the end of the XVIII century-
      70-ies of the XIX century). Communication 1. Beginning of the new style of
      medical thinking (clinical thinking)].
AB  - This communication is devoted to appearance of a qualitatively different
      methodological approach to problems of practical medicine in 1890s. This approach
      gave rise to formation of a new style of medical thinking (clinical thinking) and
      development of clinical medicine.

PMID- 22145394
TI  - [Problems of enhancement of the diagnostic capacity of medical X-ray equipment].

PMID- 22145395
TI  - [New structural materials for rotating anodes of diagnostic X-ray tubes].

PMID- 22145396
TI  - [Comparative analysis of state standard requirements to total X-ray beam
      filtering in X-ray diagnostic devices].

PMID- 22145397
TI  - [Determination of actual peak voltage from recovered spectral distributions of
      bremsstrahlung].

PMID- 22145398
TI  - [Motion estimation in angiographic images].

PMID- 22145399
TI  - [Analysis of equipment of the Russian X-ray mammological service in 2009-2010].

PMID- 22145400
TI  - [The necessity and sufficiency of technical upgrade of domestic healthcare
      service].

PMID- 22145401
TI  - [Microfocus roentgenography in medicine].

PMID- 22145402
TI  - [Methods and devices for anode voltage measurement in X-ray apparatuses].

PMID- 22145403
TI  - [Specific features of voltage converter design for mobile X-ray equipment].

PMID- 22145404
TI  - [Plasma application of protective polymer-powder coatings for ultrasonic
      sensors].

PMID- 22145405
TI  - [Methanol metabolism in plants].
AB  - Methabolism of methanol in plant organisms is considered in the paper. Enzymes of
      consecutive oxidation of methanol and enzymes responsible for incorporation of
      carbon from methanol molecule to methyl groups of phospholipids, carboxylic acids
      and carbohydrates have been described. The peculiarity of plant organisms is in
      interaction of reactions of methanol transformation with pathways of
      photorespiration and C1-metabolism and in the capacity to use methanol carbon to
      form organic matter through photosynthesis. The inclusion of methanol metabolites
      in anabolic processes occurs at the level of formaldehyde and formiate. As a
      result, exogenous methanol at low concentrations can stimulate the photosynthetic
      efficiency of plants.

PMID- 22145406
TI  - [The 5'-deoxyadenylic acid molecule conformational capacity: quantum-mechanical
      investigation using density functional theory (DFT)].
AB  - Exhaustive conformational analysis of the 5'-deoxyadenylic acid molecule, has
      been carried out by the quantum-mechanical density functional theory method at
      the MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) theory level. As many as 726 of its
      conformations have been revealed with the relative gas phase Gibbs energies under
      standard conditions from 0 to 12.1 kcal/mole. It has been shown, that the
      energetically most favorable conformation has north sugar puckering and
      synorientation of the nitrogenous base and is stabilized by intramolecular
      O(p1)H(p1)-N3 and O3'H-O(p) hydrogen bonds. Four conformations have been shown to
      have their geometry similar to that of AI-DNA and four - of BI-DNA. One conformer
      of the 5'-deoxyadenylic acid molecule is similar to its sodium salt hexahydrate
      structure in crystalline state resolved by the X-ray diffraction method and taken
      from literature. It is shown that effective charges of C4' and C5' atoms are the
      most sensitive to the molecule conformation ones. The role of the intramolecular
      OH-N hydrogen bonds in formation of the 5'-deoxyadenylic acid molecule structure
      has been demonstrated.

PMID- 22145408
TI  - [The search of microRNA genes encoded in antiparallel chains of Autographa
      californica nuclear polyhedrosis virus genome regions, including most late and
      complementary genes].
AB  - It was shown using bioinformatic approach by analysis of alternative transcriptes
      secondary structure, that A. californica nuclear polyhedrosis virus gene ph
      encoded two mature miRNAs and three potential miRNAs. Gene orf1629 complementary
      to gene ph did not encode miRNAs and pre-miRNA-Cs. Gene p10 encodes mature and
      potential miRNA. Gene p74 located on complementary chain encodes three mature
      miRNAs.

PMID- 22145407
TI  - [Energetic, conformational and electron density topological properties of 2',3'
      didehydro-2',3'-dideoxythymidine: a quantum chemical study].
AB  - Comprehensive conformational analysis of 2',3'-didehydro-2',3'-dideoxythymidine
      (d4T), also known as anti-AIDS drug stavudine, has been performed for the first
      time at the MP2/6-311++G(d,p)//DFT B3LYP/6-31++G(d,p) level of the theory. It was
      established that d4T energy landscape contained 19 local minima, which
      corresponded to stable conformers. Eight types of specific intramolecular
      interactions, which govern the d4T conformational properties, were identified,
      namely: O5'H-O2, C1'H'-O2, C6H-O5', C6H-O4', C5'H1'-O2, C5'H2'-O2, C6H-H1'C5',
      C2'-O2. The obtained results confirm the actual point of view that d4T biological
      activity is, most likely, connected with termination of the DNA chain synthesis
      in the 5'-3' direction. Thus, d4T competes with canonical thymidine in binding an
      active site of HIV-1 reverse transcriptase.

PMID- 22145409
TI  - [RNA interference of proteasome subunit of PSMbeta7 gene restricts proteasome
      subunit PSMbeta1 and PSMbeta5 mRNA expression and peptidyl-glutamyl peptide
      hydrolyzing proteasome activity in neonatal cardiomyocytes].
AB  - Using small interfering RNA (siRNA) transfection of neonatal cardiomyocytes to
      inhibit expression of nonproteolytic proteasome beta7 subunit, we observed a
      significant decrease in beta1 proteolytic subunit mRNA expression. Proteasome
      peptidyl-glutamyl peptide-hydrolyzing activity decreased to 28% (0.48 +/- 0.2 nM
      AMC/min) compared to control (1.7 +/- 0.5 nM AMC/min) (P < 0.05). Beta5 Subunit
      mRNA expression decreased 21 times (P < 0.05) with no changes in its chymotrypsin
      like activity. Proteasome trypsin-like activity and activity of another
      proteolytic enzyme tripeptidyl-peptidase II remained unchanged.

PMID- 22145410
TI  - [The liver and kidneys biochemical indices at the experimental pancreatitis in
      case of the administration of nitric oxide synthesis modulators and recombinant
      superoxide dismutase].
AB  - The rats liver and kidneys function indices were studied in case of
      administration of recombinant superoxide dismutase drug, precursor of nitric
      oxide L-arginine and the blocker of inducible NO-synthase aminoguanidine. The
      disturbances in functioning of prooxidant-antioxidant system (a decrease of
      activity of superoxide dismutase, katalaze, amount of restored glutathione,
      growth of the level of hydroperoxide lipids, TBA-active products), mitochondrial
      electron-transport pathways (a decrease in activity of succinatedehydrogenaze,
      cytochrome oxydaze), a rise of nitrite-anion level in the liver and kidneys,
      increase of alpha-amylase activity and tumor necrosis factor alpha serum
      concentration were established on the model of pancreas injury in white male
      rats. Under these circumstances aminoguanidine attenuated the oxidative stress in
      the liver and kidneys due to normalization of nitric oxide synthesis. The ability
      to activate the antioxidant system was proved by combined usage of recombinant
      superoxide dismutase and aminoguanidine. It was determined that recombinant
      superoxide dismutase partially decreases the negative influence of L-arginine and
      improves the biochemical indices of the liver and kidneys function in rats with
      acute experimental pancreatitis.

PMID- 22145411
TI  - [Fructose as a factor of Carbonyl and oxidative stress development and
      accelerated aging in the yeast Saccharomyces].
AB  - Excessive and prolonged consumption of fructose may lead to the development of
      metabolic disorders. However, the mechanisms of disturbances are still discussed.
      In the present work, the budding yeast Saccharomyces cerevisiae has been used as
      a model to compare the effects of prolonged consumption of different
      concentrations of glucose and fructose on certain physiology-biochemical
      parameters of eukaryotes. It has been shown that the yeast growth, their
      metabolic activity, intracellular level of glycogen and oxidized proteins were
      higher in cells grown on fructose. The observation is consistent with the data on
      a higher in vitro ability of fructose than glucose to initiate glycation which
      products of which are highly reactive a-dicarbonyl compounds and activated oxygen
      forms. Thus the intensity of carbonyl and oxidative stress is higher in cells
      grown on fructose. This can explain a higher rate of aging of yeast consuming
      fructose as a source of carbon and energy as compared to cells growing on
      glucose. However, carbohydrate restriction used in this study ham- pered the
      accumulation of glycogen and oxidized proteins and did not reveal any difference
      between markers of aging and carbonyl and oxidative stress in yeast grown on
      glucose and fructose.

PMID- 22145412
TI  - [Tissue specificity of antioxidant system functioning and lipid peroxidation in
      different age groups of Amur carp].
AB  - Key features of tissue enzymes functioning in antioxidant system (AOS) in
      sexually mature and immature individuals of Amur carp were studied. The activity
      of antioxidant enzymes was highest in the myocardium and subjected to age-related
      changes. It was concluded that changes in the functioning of AOS and intensity of
      lipid peroxidation processes are characterized by organ-tissue metabolic features
      and age peculiarities of metabolism that is most expressed in the myocardium.

PMID- 22145413
TI  - [Influence of heavy metal ions on the ATPase activity of actomyosin complex and
      myosin subfragment-1 from smooth muscle of the uterus].
AB  - The effect of divalent cations--Co2+, Cu2+, Mn2+ and Ni2+ (5 mM) on the activity
      of actomyosin complex ATPase and ATPase of subfragment-1 (S1,head) of myosin from
      smooth muscle of the uterus was studied. It has been shown that Co2+, Mn2+ and
      Ni2+ inhibited, while Cu2+ activates the enzyme activity of both actomyosin and
      myosin S1. Mg and Mn ions had practically no effect on the emission intensity of
      eosin Y associated with actomyosin, while one could observe the most marked
      suppression of emission of related fluorescent probe in the presence of Cu
      cations and less pronounced suppression in the presence of Co2+. In the presence
      of Mn, Co and Ni cations the average hydrodynamic diameter (HD) of actomyosin
      complex and of subfragment-1 of the smooth muscle of the uterus is virtually
      identical to the HD in the presence of Mg2+. In the presence of Cu cations there
      is a considerable (ten-fold) increase in the size of the protein particles that
      may be a result of their aggregation. The results obtained evidence for the
      significant changes in the structure and function of the actomyosin complex of
      the myometrium in the presence of heavy metals and allow us to assume that the
      target of the effect of these metals on the contractile proteins is a subfragment
      1 of myosin, where the active site of ATPase and actin-binding sites are
      localized.

PMID- 22145414
TI  - [Effect of high sodium chloride concentrations on the pigment content and free
      radical processes in corn seedlings leaves].
AB  - The effect of sodium chloride on general morphometrical parameters of seedlings,
      and biochemical parameters in the leaves of corn seedlings was studied. Exposure
      to 100 and 200 mM NaCl slowed down the growth of stem and roots, whereas 100 and
      200 mM NaCl during 24 h enhanced the concentration of chlorophylls, carotenoids,
      anthocyans, and thiobarbituric acid reactive substances. The decrease in protein
      carbonyl groups was found at 24-hour exposure to 200 mM salt. The treatment
      during 24, 48 and 72 h to 200 mM salt increased the level of total and high
      molecular mass thiols, whereas low molecular mass thiol content was by 20-25%
      higher at 48 h exposure to all used salt concentrations. The activity of guaiacol
      peroxidase was higher only at 24 h exposure to 100 and 200 mM salt, and catalase-
      at 50 mM during 48 h. At 72-hour exposure, catalase activity was by 27 and 41%
      higher in seedlings, exposed to 50 and 200 mM NaCl, respectively. Therefore, it
      is concluded the plant exposure to 50-200 mM salt initially developed oxidative
      stress, inducing adaptive response--an increase in antioxidant potential and
      efficiency of systems of energy production. That results in plant adaptation to
      unfavourable conditions.

PMID- 22145415
TI  - [The effect of potassium different concentrations on mRNA expression of protein
      StAR and cytochrome p-450(SCC) in human adrenocortical tissue].
AB  - The effect of different potassium concentrations on changes in steroidogenic
      acute regulatory protein (StAR) and cytochrome P-450(SCC) in human adrenal cortex
      tissue was studied. A rise in K+ concentration in incubation medium to 8.5 mM
      caused an increase in StAR and cytochrome P-450(SCC) mRNA level in
      adrenocorticocytes by 70 and 76%, respectively, compared with control. Thus,
      potassium ions caused an enhancement of minerocorticoid synthesis in the adrenal
      cortex, which is associated with mechanisms that regulate the intensity of
      expression of StAR and cytochrome P-450(SCC) on a transcriptional level.

PMID- 22145416
TI  - [Metal-binding capacity of metallothioneins of the liver of rats poisoned with
      heavy metals].
AB  - The functioning of metallothioneins in the liver of rats, poisoned with copper
      sulfate and cadmium sulfate has been investigated. By sequential chromatography
      on sephadex G-50 and DEAE-cellulose the authors obtained metallothioneins (MT-1,
      MT-1A, MT-2, MT-2a), which differ in molecular weight and composition of
      associated metals. Heavy metal poisoning leads to activation of synthesis and
      metal-binding function of metallothioneins, as well as to changes in the
      composition of their isoforms.

PMID- 22145418
TI  - [Psychotherapy research in childhood and adolescence].

PMID- 22145417
TI  - [Investigation of the properties and functioning of the nervous cells membranes
      Na+, K+-ATPase in the works of the Department of Biochemistry of Nervous System
      of Palladin Institut of Biochemitry, NAS of Ukraine (1960-2000)].

PMID- 22145419
TI  - [History of empirical psychotherapy research with special reference to the
      psychotherapy with children and adolescents].
AB  - In the first fifty years of modern psychotherapy, most psychotherapists believed
      that it was not possible to investigate the efficacy of psychotherapy by means of
      empirical-statistical methods. Only in the second half of the 20th century,
      systematic psychotherapy research was initiated. Since this time a dynamic
      development of psychotherapy research can be observed, resulting in a rapidly
      growing knowledge base about processes and outcomes. In the first phase of
      research, the general question had to be answered, whether psychotherapy is able
      at all to cause the desired effects. After it had become evident that
      psychotherapy results are undoubtedly impressive, research emphasis was placed on
      the question "What works for whom" i. e. which therapy packages are effective for
      specific disorders. This disorder-specific research tasks are still prevailing;
      but now, after the first decade of the 21st century psychotherapy, research is
      confronted with additional and new challenges, which are outlined in the article.

PMID- 22145420
TI  - [Efficacy of psychotherapy with children and adolescents].
AB  - Psychotherapeutic interventions require empirical as well as scientific
      assessment. Specifically, the proven efficacy of psychotherapy for children and
      adolescents is essential. Thus, studies examining treatment efficacy and meta
      analyses are necessary to compare effect sizes of individual therapeutic
      interventions between treatment groups and waiting control groups. Assessment of
      138 primary studies from 1993-2009 documented the efficacy of psychotherapy for
      children and adolescents. Furthermore, behavioural therapy outperformed non
      behavioural interventions, as 90% of behavioural interventions showed larger
      effect sizes compared to non-behavioural psychotherapy. Analysis of moderator
      variables demonstrated an improved treatment efficacy for individual therapy,
      inclusion of the family, treatment of internalised disorders, and in clinical
      samples. Stability of psychotherapeutic treatment effects over time was
      demonstrated.

PMID- 22145421
TI  - [How specific is the evidence base for child and adolescent psychotherapy?].
AB  - Evidence-based psychotherapy (EBP) proposes the fit between a specific treatment,
      therapist, patient and mental disorder. At the same time, the generalization of
      psychotherapy research findings is intended. In this conflict between
      individualized and standardized treatment the search for specific active
      components of psychotherapy is essential to improve intervention methods as well
      as training of therapists. Many manualized treatments for children and
      adolescents are considered evidence-based, proven by its outcome. However, their
      active ingredients often remain unclear. The following methods to identify
      necessary active components for successful treatments are described: classical
      comparative randomized controlled trials, dismantling studies, add-on studies,
      meta-analyses, and the multiphase optimization strategy. Consequences for the
      future agenda for child and adolescent psychotherapy research are discussed.

PMID- 22145422
TI  - [Psychoanalytic psychotherapy with adolescents: challenges, technical problems,
      and treatment outcome].
AB  - Psychoanalytic treatment of adolescents has a long tradition and is currently one
      of the most frequent treatments in this age group. However, not many studies
      document the efficacy of psychoanalytic treatments of adolescents. This article
      analyses the background of this deficit by focusing on recent changes in
      symptomatology, the widespread diagnostic insecurity and the special challenges,
      which such treatment demands of the therapist. The task of researching the
      efficacy of adolescent psychotherapy is of considerable complexity. Recent own
      studies about efficacy of adolescent therapy will be presented. The evidence
      suggests that different approaches in therapy (psychoanalytic vs. psychodynamic)
      are of similar efficacy. However, long-term treatments ensure a consolidation of
      symptom reduction. The inclusion of different perspectives (adolescent, parents,
      therapist) and work with parents may be effective.

PMID- 22145423
TI  - [The usage of neurofeedback in children with ADHD: the method and its
      evaluation].
AB  - Neurofeedback is a computer-based behavior training, which is gaining increasing
      interest in the treatment of children with attention-deficit/hyperactivity
      disorder (ADHD). This article gives an introduction to neurofeedback and
      summarizes the state of research, discussing inter alia methodical aspects (e.
      g., requirements to a control training). Evaluation studies conducted so far
      indicate clinical efficacy. For example, neurofeedback training was superior to a
      computerized attention training in a randomized controlled trial (medium effect
      size). Follow-up investigations suggest that treatment effects remain stable (at
      least six months). At the clinical level, comparable improvements could be
      obtained for the neurofeedback protocols theta/beta training and training of slow
      cortical potentials. Neurophysiological findings document different mechanisms of
      theta/beta training and slow cortical potential training. Future studies should
      further elucidate the specificity of training effects related to the kind of
      training and certain disorders and address how to optimize and individualize
      neurofeedback training.

PMID- 22145424
TI  - [Inpatient cognitive-behavioral therapy of adolescents with anxious-depressed
      school absenteeism: changes during treatment and stability over time].
AB  - 90 adolescents with chronic anxious-depressed school absenteeism underwent
      inpatient cognitive-behavioral therapy. A strong, highly significant decline of
      school absenteeism, anxiety and depressive symptoms rated by parents and
      youngsters was found. Reductions remained stable over a two months follow-up
      period. A cautious interpretation of the results is important because of the lack
      of a control condition.

PMID- 22145425
TI  - [Separation anxiety family therapy (SAFT): a cognitive behavioral treatment
      program for children suffering from separation anxiety].
AB  - Separation Anxiety Disorder is one oft the most frequent mental disorders in
      children. The SAFT treatment manual is an evidence-based cognitive behavioral
      therapy program for children with separation anxiety. Its first part consists of
      four weekly sessions with the child and four weekly sessions with the parents.
      Children and parents receive psychoeducation about anxiety, learn to recognize
      and reframe irrational beliefs about separation situations, expand their
      repertoire of coping strategies, and are introduced to the rationale for
      exposure. The second part of treatment consists of eight weekly family sessions
      followed by a short parent-only session. During the family sessions, exposure in
      vivo is planned and practiced. The parent-only portions of the family sessions
      involve reframing parental irrational beliefs about separation, parenting
      strategies and practicing parental behavior during exposure. Evaluation data
      shows that disorder-specific family-based therapy (SAFT) results in improvement
      compared with waiting list controls.

PMID- 22145426
TI  - [Quality of life].

PMID- 22145427
TI  - [It is necessary that the quality and safety of care is always guaranteed
      [interview by Yasmina Ouharzoune].

PMID- 22145428
TI  - [The Fourcade law integrates nurses in new primary care structures].

PMID- 22145429
TI  - [Pain assessment and care project].
AB  - The concept of "quality" in relation to the treatment of pain is an obligation
      for institutions and professionals as well as a right for patients. It is
      worthwhile recalling the importance of the nurse's role in treating pain and in
      particular in its assessment. Assessment can only be carried out with the use of
      adapted and validated tools and the support of the whole team. A department-wide
      project is therefore necessary.

PMID- 22145431
TI  - [Socialisation, a fundamental process for student nurses].
AB  - Socialisation is an essential part of learning the nursing profession. Through
      it, students develop, during the theoretical training and practical placements,
      various strategies and resources to help them acquire the skills required to be a
      professional nurse. Numerous studies demonstrate the importance and interest of
      the socialisation process.

PMID- 22145430
TI  - [The place of ethics in patient empowerment].
AB  - Therapeutic education teaches patients how to understand, grasp and take personal
      charge of their pathology. This freedom of choice and action can cause patients
      to feel guilty, especially if their condition worsens. How should this form of
      empowerment be managed, by the caregiver as well as the patient? Questioning of
      an ethical nature is therefore necessary.

PMID- 22145432
TI  - [Mobile diabetology team, a new form of patient care].
AB  - Diabetes is a pathology whose complications affect all of the body's organs.
      Increasing numbers of diabetic patients are being hospitalised in various
      hospital departments. To ensure a quicker, more efficient and better quality of
      care, and to encourage the training of professionals in diabetology, the
      endocrinology department at Bicetre university hospital decided to create a
      mobile diabetology team, following a study carried out in 2008.

PMID- 22145433
TI  - [Quality of life and health. Quality of life, an essential concept difficult to
      measure].

PMID- 22145434
TI  - [The concept of quality of life in healthcare, a complex definition].
AB  - The concept of quality of life in healthcare, a complex definition. The
      assessment of quality of life occupies a central place in the field of
      healthcare. Extensive research was carried out into the subject during the 20th
      century. Ojectifying a subjective and multi-dimensional concept remains a
      difficult task. Several societal, economic and epistemological factors must be
      taken into account.

PMID- 22145435
TI  - [Measurements of quality of life, construction and validation of an instrument].
AB  - Developing and validating an instrument to measure quality of life is a
      complexundertaking. The main stages of such a process extend from the creation of
      a tool through conceptual, qualitative and quantitative phases to the main
      notions relating to its validation: reliability and validity of the measurement,
      sensitivity to changes.

PMID- 22145436
TI  - [A plan for the improvement in the quality of life of people suffering from
      chronic diseases].
AB  - In 2007, the French Ministry of Health launched a plan devoted to the improvement
      of the quality of life of patients suffering from chronic diseases. Over the last
      four years this plan has resulted in a number of concrete actions: events and
      seminars have been organised, patients' education has obtained legislative
      recognition and several partnerships have been created. Time for a progress
      report.

PMID- 22145437
TI  - [The specificities of the assessment of quality of life in psychiatry].
AB  - Psychiatry, like other medical disciplines, has integrated the assessment of
      quality of life into the various parameters necessary for the monitoring of a
      patient's healthcare project. However, some specificities exist, inherent to the
      repercussions of the pathology on the subjective experience and its expression as
      well as to the patient's mode of treatment.

PMID- 22145438
TI  - [Quality of life linked to health in medical economic studies].
AB  - Quality of life plays an established role in public decision making. In the area
      of health economics, quality of life indicators have become an essential tool in
      decision analysis.

PMID- 22145439
TI  - [Recommendations on the quality of life of dependent elderly people].
AB  - The French national agency for the assessment and quality of social and medical
      social institutes and services (ANESM) recently published recommendations aiming
      to promote the quality of life of elderly people in nursing homes. These
      recommendations take into account the specific characteristics of the quality of
      life of this sector of the population.

PMID- 22145440
TI  - [Criteria and tools for assessing quality of life in palliative care].
AB  - The concepts of quality of life and palliative care seem at first sight to be
      inextricably linked. However, it is worth questioning the interest of tools for
      assessing quality of life in the practice of palliative care. Effectively, these
      tools can have harmful consequences on the patient and provoke notably a loss of
      self-esteem.

PMID- 22145441
TI  - [Quality of life at work and quality of work].
AB  - Unease at work is the consequence of a growing difficulty in carrying out high
      quality work based on performance criteria. Healthcare professionals are well
      placed to highlight these criteria which can be discussed within work groups. The
      aim of these groups is to work towards compromises combining efficiency and
      health.

PMID- 22145442
TI  - [A concept of the quality of life in "client-centered" health care].

PMID- 22145443
TI  - [Quality of life. Bibliography].

PMID- 22145444
TI  - [Aggression, violence and stress].

PMID- 22145445
TI  - IGF-I in extremely low birth weight (ELBW): a long-term observation.

PMID- 22145447
TI  - Intracranial hypertension in pediatric patients treated with recombinant human
      growth hormone: data from 25 years of the Genentech National Cooperative Growth
      Study.
AB  - Intracranial hypertension (IH) is a rare condition in children. However, a
      relationship between recombinant human growth hormone (rhGH) therapy and IH has
      been well documented. Risk factors were assessed for 70 rhGH-naive patients
      enrolled in the National Cooperative Growth Study with reports of IH after
      treatment initiation. Patients with severe growth hormone deficiency, Turner
      syndrome, chronic renal insufficiency (CRI), and obesity (particularly in the CRI
      group) were at highest risk of developing IH during the first year of therapy,
      suggesting initiation of careful early monitoring. In some patients, factors such
      as corticosteroid use or other chromosomal abnormalities appear to confer a
      delayed risk of IH, and these patients should be monitored long-term for signs
      and symptoms of IH.

PMID- 22145448
TI  - Effects of recombinant human growth hormone on protein turnover in the fasting
      and fed state in adolescents with Crohn disease.
AB  - The primary purpose of this study was to test whether recombinant human growth
      hormone (rhGH) supplementation would enhance protein synthesis and accretion of
      lean body mass. Eight adolescents (six males and two females; 17.2 +/- 2.6 years;
      age range, 13.7-21.2 years) participated in a randomized double-blind placebo
      controlled cross-over trial of rhGH. We employed stable isotopes to measure
      proteolysis and protein synthesis during fasting and fed conditions during two 6
      month treatment conditions. We also measured bone mineral density (BMD), markers
      of bone turnover, and body composition. Whole-body proteolysis, phenylalanine
      catabolism, and protein synthesis did not differ during treatment with rhGH vs.
      placebo. Enteral nutrition suppressed proteolysis and increased protein synthesis
      similarly during placebo and rhGH treatments. We conclude that rhGH is unlikely
      to provide sufficient metabolic benefit to warrant its use as an adjunct
      treatment in clinically stable adolescents with Crohn disease. A high prevalence
      of vitamin D deficiency and suboptimal BMD existed, which deserves further
      investigation and clinical attention.

PMID- 22145446
TI  - A potential role for adjunctive vitamin D therapy in the management of weight
      gain and metabolic side effects of second-generation antipsychotics.
AB  - Second-generation antipsychotic (SGA) medications introduced about 20 years ago
      are increasingly used to treat psychiatric illnesses in children and adolescents.
      There has been a five-fold increase in the use of these medications in U.S.
      children and adolescents in the past decade. However, there has also been a
      parallel rise in the incidence of side effects associated with these medications,
      such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite
      the severity of these complications and their financial impact on the national
      healthcare budget, there is neither a clear understanding of the mechanisms
      contributing to these side effects nor the best ways to address them. Studies
      that examined lifestyle modification and pharmaceutical agents have yielded mixed
      results. Therefore, clinical studies using agents, such as vitamin D, which are
      inexpensive, readily available, with low side effects profile, and have
      mechanisms to counteract the metabolic side effects of SGA agents, are warranted.
      Vitamin D is a prohormone with skeletal and extraskeletal properties that could
      potentially reduce the severity of these metabolic side effects. Its role as an
      adjunctive therapy for the management of metabolic side effects of SGA agents has
      not been adequately studied. Effective strategies to curb these side effects will
      improve the overall health of youths with psychiatric illnesses who receive SGAs.
      Herein we present a pilot study on the use of vitamin D in patients on treatment
      with SGAs.

PMID- 22145449
TI  - Circular IGFBP-3 level affected by the gene transfer of different growth hormone
      isoforms.
AB  - To evaluate whether through gene transfer, which growth hormone (GH) isoform can
      influence the circulation IGFBP-3 level, mice were injected three times with the
      human cytomegalovirus (CMV) mediated mammalian expression vector encoding
      different GH isoform gene. Then blood samples were drawn and the ELISA method was
      used to determine the circulation concentration of IGFBP-3. It was found that the
      22 kDa GH gene could increase IGFBP-3 levels to 1.94 microg/ mL whereas 20 kDa
      GH, 17 kDa GH and 5 kDa GH genes did not play a role in the circulation
      expression of IGFBP-3.

PMID- 22145450
TI  - Changes in plasma FGF23 in growth hormone deficient children during rhGH therapy.
AB  - BACKGROUND: Children with growth hormone deficiency (GHD) have increased renal
      phosphorus reabsorption during rhGH therapy, Fibroblast growth factor 23 (FGF23)
      is a known regulator of serum phosphorus and may be responsible for this effect.
      METHODS: Prospective study in GHD children investigating changes in plasma C
      terminal FGF23 (C-FGF23), markers of mineral metabolism, and insulin-like growth
      factor (IGF-1) in the first year of rhGH therapy. Normal stature children served
      as baseline controls. RESULTS: The two groups at baseline were similar, except
      GHD patients had lower baseline TmP/GFR vs. controls (p < 0.05). C-FGF23 in GHD
      patients trended upward at follow-up 1 (p = 0.058) and significantly increased at
      follow-up 2 (p = 0.0005) compared to baseline. TmP/GFR also rose at follow-up 1
      (p = 0.002) and follow-up 2 (p = 0.027). The C-FGF23 rise persisted after
      adjusting for age, gender, sex, total calcium, and phosphorus (p < 0.01) but
      attenuated after adjusting for TmP/GFR or IGF-1. CONCLUSIONS: C-FGF23 rises
      during rhGH therapy in spite of increased Tmp/GFR, an unanticipated observation
      given the role of FGF23 as a phosphaturic factor. The C-FGF23 rise may be a
      secondary response during rhGH therapy.

PMID- 22145451
TI  - Insulin-like growth factor-1 (IGF-1) serum concentration among 7-year-old
      extremely low birth weight children--an indicator of growth problems.
AB  - BACKGROUND: The study aim was to compare somatic development, body composition,
      insulin growth factor-1 (IGF-1) serum concentration and serum lipid profile
      between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA)
      7-year-old extremely low birth weight (ELBW) children and full-term (FT)
      controls. MATERIALS AND METHODS: Fifty-seven AGA ELBW children [mean birth weight
      (BW) 850 g and mean gestational age (GA) 26.4 weeks] and 24 SGA ELBW children
      (mean BW 833 g, mean GA 29.5 weeks) were evaluated. The control group included 37
      age- and sex-matched FT children from one outpatient center. RESULTS: Nine AGA
      and four SGA were found to have short stature defined as height < 3rd percentile
      for chronological age (p = 0.9). In the AGA cohort, the results of weight, head
      circumference, triceps skin fold and body mass index (BMI) measurements were
      significantly reduced in the short-stature subgroup. IGF-1 serum concentrations
      differed significantly between short-stature and normal-stature subgroups (121
      vs. 193 ng/mL; p = 0.02). In the SGA cohort, weight and serum concentrations of
      total cholesterol (5.03 vs. 4.26 mmol/L; p = 0.04), LDL cholesterol (3.24 vs.
      2.38 mmol/L; p = 0.01) and IGF-1 (113 vs. 211 ng/mL; p = 0.01) differed
      significantly between the short-stature and normal-stature subgroups.
      CONCLUSIONS: Short stature at the age of 7 years was diagnosed in a similar
      percentage of AGA and SGA former ELBW infants. In both cohorts short-stature
      children have significantly lower weight and serum IGF-1 levels. IGF-1 seems to
      be involved in prolonged growth restriction among ELBW infants, regardless of
      whether they were AGA or SGA.

PMID- 22145452
TI  - The effect of the length of the prodromal period on the metabolic control within
      the first 2 years in children with diabetic ketoacidosis manifestation.
AB  - PURPOSE: We investigated the effects of clinical and laboratory properties at the
      time of the initial application of patients recently diagnosed and presenting
      metabolic indicators of diabetic ketoacidosis who were given disease prognoses in
      years 1 and 2 after discharge. MATERIALS AND METHODS: A total of 94 patients
      admitted to Bakirkoy Maternity and Children's Diseases Training and Research
      Hospital with diabetic ketoacidosis and recently diagnosed with type 1 diabetes
      mellitus were investigated. Patient files were examined within 2 years following
      discharge. FINDINGS: All 94 study patients (53.2% male and 46.8% female)
      presented acidosis, ketonuria and hyperglycemia. While a moderate correlation was
      detected between the prodromal period and HbA(1c) values in year 1, only a slight
      correlation was seen in HbA(1c) values in year 2. In addition, a slight
      correlation was observed between the prodromal period and the number of
      hospitalizations due to diabetic ketoacidosis in the first year. Again, while a
      moderate correlation was observed between HbA(1c) values and the number of
      hospitalizations due to diabetic ketoacidosis in year 1, only a slight
      correlation was seen in year 2. The prodromal period was directly proportional to
      patient age. RESULTS: Hospital admissions may be reduced through appropriate
      treatment, follow-up and metabolic control of patients with type 1 diabetes
      mellitus. In addition, we report a relationship between the prodromal period and
      HbA(1c) values in type 1 diabetes patients.

PMID- 22145453
TI  - Clinical characteristics at presentation of type 1 diabetes mellitus in children
      younger than 15 years in Croatia.
AB  - The aim of the study was to determine the clinical and biochemical
      characteristics of type 1 diabetes mellitus (DM) at presentation in children
      younger than 15 years in Croatia during a 9-year period, with special attention
      to diabetic ketoacidosis (DKA) incidence. The registered data set comprised blood
      glucose, pH, serum bicarbonate levels, and clinical symptoms at disease
      manifestation. During the study period, 692 children were diagnosed with type 1
      DM. Polydipsia (96.7%), polyuria (96.05%), and weight loss (82.7%) were the most
      frequent symptoms anticipating disease detection. Enuresis was recorded in
      11.55%. A total of 36.41% patients had DKA (pH < 7.3) at disease onset. During
      the 9-year period, the percentage of children presenting with DKA at time of
      diagnosis decreased from 41.67% to 33.33% (z = 1.68, p = 0.046). A positive
      family history of DM, the only factor with an impact on the DKA incidence rate in
      our population, lowers the probability of the development of ketoacidosis. This
      study confirms the importance of the detection of the classic symptoms of
      polyuria, polydipsia, and weight loss in patients with new-onset type 1 DM. The
      percentage of patients with DKA at diabetes onset decreased during the observed
      period but is still high and includes one-third of all patients. This is why in
      every acutely ill child, especially at a younger age, one should evaluate the
      possibility of type 1 DM to avoid the development of ketoacidosis.

PMID- 22145454
TI  - Umbilical cord oxidative stress in infants of diabetic mothers and its relation
      to maternal hyperglycemia.
AB  - AIMS: There is growing body of evidence that oxidative stress plays an important
      role in the pathogenesis of diabetes mellitus (DM) and in development of maternal
      and fetal complications of diabetic pregnancies. The aim of the present study was
      to investigate total antioxidant capacity (TAC), total oxidant status (TOS), and
      oxidative stress index (OSI) in infants of diabetic mothers (IDM) and to reveal
      the influence of maternal hyperglycemia on these parameters. METHODS: A
      prospective controlled study was conducted between March 2010 and November 2010.
      Umbilical cord blood was taken from IDM and controls for TAC and TOS measurement,
      and OSI was calculated. IDM were divided into two groups, either of mothers
      treated with insulin during pregnancy or of those treated with a carbohydrate
      restricted diet. RESULTS: Thirty-six IDM and 14 infants born to non-diabetic
      mothers were enrolled. Infants of insulin-treated mothers (group 1) and infants
      of mothers managed with a carbohydrate-restricted diet (group 2) had
      significantly higher TOS (p < 0.001 and p = 0.001, respectively) and OSI (p <
      0.001 and p = 0.001, respectively) levels compared to controls. However, TAC
      levels were similar in all three groups. Maternal HbA(1c) values were correlated
      to TOS (p < 0.001, r = 0.694) and OSI (p < 0.001, r = 0.683). CONCLUSIONS:
      Oxidative stress is increased in IDM, and a significant relation exists between
      the degree of maternal hyperglycemia in pregnancy and oxidative stress in the
      newborn at birth.

PMID- 22145455
TI  - The relationship between serum magnesium levels with childhood obesity and
      insulin resistance: a review of the literature.
AB  - BACKGROUND: Magnesium, the second most abundant intracellular cation, plays a
      major role in regulating insulin effect and insulin mediated glucose uptake. It
      has been shown that serum magnesium levels were negatively correlated with HOMA
      IR (homeostasis model of insulin resistance) index. AIM: To investigate the
      relationship between serum magnesium levels with obesity and insulin resistance
      in childhood. METHODS: Two hundred and three children and adolescents (117 obese
      children and 86 controls) were included. Obese cases were also subgrouped
      according to the presence or absence of insulin resistance (IR) as "IR (+) obese"
      and "IR (-) obese", respectively. Serum glucose, insulin and magnesium levels
      were measured after a 12-h fasting at 8-8.30 a.m. We assessed insulin sensitivity
      by using HOMA-IR index as a surrogate marker of insulin resistance. RESULTS:
      Serum levels of magnesium were significantly lower in the IR (+) obese group than
      controls (p = 0.014). At the same time, there was a positive correlation between
      serum magnesium levels and body mass index-standard deviation score (BMI-SDS) (r
      = -0.28, p = 0.03) in the IR (-) obese group. CONCLUSIONS: Low serum magnesium
      levels may contribute to the development of insulin resistance in obese children.

PMID- 22145456
TI  - Fulminant type 1 diabetes mellitus in Korean adolescents.
AB  - Fulminant type 1 diabetes has recently been identified as a new subtype of
      idiopathic diabetes that is mostly found in Japanese adults. The aim of this
      study was to investigate the frequency as well as the clinical and laboratory
      characteristics of fulminant type 1 diabetes among Korean children with childhood
      onset type 1 diabetes. One-hundred and fifty patients that had been newly
      diagnosed with type 1 diabetes over the past 10 years were included. These
      patients came from three hospitals. Out of the 150 patients, two female patients
      fulfilled the criteria for fulminant type 1 diabetes. They were negative for
      islet autoantibodies. The patients with fulminant type 1 diabetes had an older
      age of onset and a lower HbA1c than the patients with autoimmune or idiopathic
      type 1 diabetes. In addition, the patients with fulminant type 1 diabetes had
      increased serum aspartate aminotransferase, alanine aminotransferase and amylase
      levels, and decreased fasting serum C-peptide levels. The frequency of fulminant
      type 1 diabetes was 1.33% among all patients newly diagnosed with type 1 diabetes
      under the age of 16. Although this type of diabetes is more commonly an adult
      onset disease, it is possible that fulminant type 1 diabetes has not yet been
      fully recognized in children and adolescence, and may be more common than
      initially thought.

PMID- 22145457
TI  - Retinol-binding protein 4 correlates with triglycerides but not insulin
      resistance in prepubertal children with and without premature adrenarche.
AB  - BACKGROUND: Retinol-binding protein 4 (RBP4) has been proposed as an early marker
      for insulin resistance (IR), but no prior studies have addressed RBP4 in an
      exclusively prepubertal population. Children with premature adrenarche (PA) are
      at increased risk for IR and metabolic syndrome (MeS); thus finding an
      appropriate early marker for IR in this population would allow for early
      intervention and prevention of morbidity related to IR and MeS. OBJECTIVE: To
      determine whether prepubertal children with PA have higher levels of RBP4 than
      controls and whether RBP4 correlates with comorbidities of metabolic disease in
      prepubertal children. SUBJECTS: This study comprised 49 prepubertal children (24
      with PA and 25 control subjects), 20 boys and 29 girls, who were between the ages
      of 5 and 9 years. METHODS: This was a cross-sectional, case-control study
      conducted in a subspecialty ambulatory clinic based in a quaternary care center.
      RBP4 levels, hormonal values, lipids, and response to an oral glucose tolerance
      test were evaluated in children with PA and controls, and body composition
      measures were obtained in a subset of patients (n = 18). RESULTS: RBP4 correlated
      with triglycerides (r = 0.57, p < 0.0001) but did not correlate with IR in a body
      mass index z-score-adjusted Pearson correlation analysis. There was no difference
      in RBP4 levels between the PA and control groups. CONCLUSIONS: These findings
      suggest that RBP4 may be an early marker of dyslipidemia, which may herald future
      onset of hepatic IR, polycystic ovary syndrome, and MeS.

PMID- 22145458
TI  - The energy expenditure of an activity-promoting video game compared to sedentary
      video games and TV watching.
AB  - BACKGROUND: In the present study we investigated the effect of television
      watching and the use of activity-promoting video games on energy expenditure in
      obese and lean children. METHODS: Energy expenditure and physical activity were
      measured while participants were watching television, playing a video game on a
      traditional sedentary video game console, and while playing the same video game
      on an activity-promoting video game console. RESULTS: Energy expenditure was
      significantly greater than television watching and playing video games on a
      sedentary video game console when children played the video game on the activity
      promoting console. When examining movement with accelerometry, children moved
      significantly more when playing the video game on the Nintendo Wii console.
      CONCLUSION: Activity-promoting video games have shown to increase movement, and
      be an important tool to raise energy expenditure by 50% when compared to
      sedentary activities of daily living.

PMID- 22145459
TI  - Acanthosis nigricans and truncal fat in overweight and obese children.
AB  - BACKGROUND: Screening for acanthosis nigricans (AcN) in overweight children is
      repeatedly recommended. The significance of AcN, and its relation to central
      obesity in children, is unclear. OBJECTIVE: To compare clinical and
      anthropometric parameters associated with adiposity, between overweight and obese
      children with and without AcN. METHODS: One hundred and forty-nine overweight and
      obese children were screened for AcN. Height, weight, waist and hip
      circumferences, triceps skinfold thickness and segmental body fat amounts were
      measured. RESULTS: Twenty-two (14.8%) children had AcN. Children with AcN had
      greater height, weight, BMI, waist circumference, waist-to-height-ratio, triceps
      skinfold thickness, and total and truncal body fat percentage, compared to those
      without AcN. After adjustment for age and BMI, no adiposity measure was increased
      in children with AcN. CONCLUSION: Overweight and obese children with AcN
      basically have greater overall and central adiposity, than those without it.
      Adjusting for BMI, there is no evidence for increased abdominal fat in these
      children.

PMID- 22145460
TI  - The effects of antiepileptic drugs on the relationships between leptin levels and
      bone turnover in prepubertal children with epilepsy.
AB  - Antiepileptic drugs (AED) had an effect on bone metabolism in children. This
      study was conducted in order to determine the relationships between serum leptin
      levels, bone mineral density (BMD) and bone turnover markers in epileptic
      children. Fifty-three patients were treated with valproic acid (VPA) and 23 with
      carbamazepine (CBZ) monotherapy; 50 healthy children were included in the study
      as controls. Serum alkaline phosphatase (ALP) and cross-linked C-telopeptide
      (CTx) levels were statistically significantly higher in the CBZ group than in the
      VPA group and the control group (p < 0.0001, p < 0.010, respectively). Serum
      osteocalcin and ALP levels were significantly lower in the VPA group than in the
      control group (P < 0.012, P < 0.030, respectively). Although we found slightly
      higher serum leptin levels in both the CBZ and VPA groups, they were not
      significantly different from the control group (P > 0.05). We demonstrated that
      the markers of bone formation and resorption increased with CBZ and decreased
      with VPA treatment without affecting BMD and vitamin D levels in prepubertal
      epileptic children.

PMID- 22145461
TI  - The association between morning cortisol and adiposity in children varies by
      weight status.
AB  - OBJECTIVE: To examine the associations between morning cortisol and adiposity in
      children at baseline and 9-month follow-up. METHODS: Participants included 649
      (301 males, 348 females) children (9.6 +/- 0.9 years) for the cross-sectional
      analysis and 316 (153 males, 163 females) for the longitudinal analysis. Body
      mass index (BMI, kg/m2) was calculated from measured height and weight and waist
      circumference (WC, cm) was measured at the superior border of the iliac crest.
      Cortisol was assessed via saliva samples collected on a single morning. Cross
      sectional and longitudinal analyses were conducted to examine the relationships
      between cortisol and adiposity. RESULTS: Approximately 31% were overweight
      (17.7%) or obese (12.8%). The mean cortisol level was 9.36 +/- 5.64 nmol/L (0.34
      +/- 0.20 microg/dL). At baseline, no significant correlations were found between
      cortisol and BMI or WC (r < 0.07). Baseline cortisol did not correlate with
      change in BMI z-score (r = -0.03) or WC (r < -0.01) over the follow-up period.
      When examined by weight status, baseline cortisol was significantly related to
      changes in WC (r = 0.32) and BMI z-score (r = 0.28) among overweight subjects.
      CONCLUSIONS: A positive relationship was found between morning cortisol and
      change in WC over 9 months in overweight children. Future studies should examine
      the association between 24-h cortisol patterns and direct measures of trunk fat.

PMID- 22145462
TI  - Evaluation of two dietary treatments in obese hyperinsulinemic adolescents.
AB  - Hyperinsulinemia increases the risk of cardiovascular disease in obese children.
      Only a few treatments are available to decrease insulin resistance. The reduction
      of hyperinsulinemia by dietary means would be a simple, physiologic and economic
      way to reduce the risk of metabolic disease. OBJECTIVE: To compare the effects of
      two low-energy diets on serum insulin concentrations and weight loss in obese
      hyperinsulinemic adolescents. MATERIALS AND METHODS: Eighty-six randomly assigned
      insulin-resistant obese adolescents completed a 16 week calorie-restricted diet.
      The experimental diet had a reduced glycemic index designed to evoke a low
      insulin response (LIR), with carbohydrates and proteins ingested in separate
      meals. The control diet was a conventional (CD) with similar proportions (60%,
      20% and 20%). Variables studied were blood glucose and insulin concentrations
      after an oral glucose load, body mass index, waist circumference, and insulin
      resistance (homeostasis model assessment, HOMA). RESULTS: Mean weight [+/-
      Standard Deviation (SD)] was significantly reduced after the LIR (-0.53 +/- 0.5)
      and the CD (-0.54 +/- 0.4), but a greater decrease of waist circumference (cm)
      was observed after the LIR (-9.1 +/- 4.8 vs. -6.6 +/- 4.6, p = 0.02). Fasting
      insulin concentrations (-17.9 +/- 27.9 vs. -9.4 +/- 14.8, p = 0.01) and HOMA
      dropped significantly more after the LIR than after the CD (-3.5 +/- 4.9SD vs. 
      2.4 +/- 1SD, p < 0.0001). CONCLUSIONS: The LIR diet reduces serum insulin
      concentrations and waist circumference more than conventional treatment and
      appears to be a promising alternative to a conventional diet in insulin-resistant
      obese adolescents. Long-term follow-up is needed to evaluate the maintenance of
      weight loss and metabolic parameters.

PMID- 22145463
TI  - Early cardiac abnormalities and serum N-terminal pro B-type natriuretic peptide
      levels in obese children.
AB  - OBJECTIVE: The aim of this study was to evaluate early cardiac abnormalities in
      obese children by the conventional echocardiography and to verify whether N
      terminal pro B-type natriuretic peptide (NT-proBNP) differ between obese and
      healthy children. METHODS: We started this study with 68 obese children and 35
      healthy controls matched for age and sex. Body mass index (BMI) was calculated.
      Children with a BMI > or = 95th percentile were considered obese. Thirty children
      in the obese group were also diagnosed with metabolic syndrome, according to the
      International Diabetes Federation criteria. Standard echocardiographic study was
      performed on each patient and control subject. Diastolic filling parameters were
      evaluated using pulsed-wave tissue Doppler method. Blood samples were taken at 8
      a.m. to study blood biochemistry tests, including insulin, lipids, glucose, and
      NT-proBNP. Serum NT-proBNP levels were measured by a solid-phase, enzyme-labeled
      chemiluminescent immunometric assay. Homeostasis model assessment of insulin
      resistance (HOMA-IR) was calculated. Children with HOMA-IR > 3.16 were considered
      insulin-resistant. RESULTS: There were diastolic filling abnormalities in obese
      children, as shown by a decreased mitral valve early filling (E) wave/late
      filling (A) ratio and a prolongation in E-wave deceleration time. The levels of
      NT-proBNP were not statistically different among the groups. The levels of NT
      proBNP were not different between obese children with and without metabolic
      syndrome, those with and without hypertension, and those with and without insulin
      resistance, respectively. CONCLUSION: Although there were diastolic filling
      abnormalities in obese children, their NT-proBNP levels were not different from
      healthy controls. It seems that there is no diagnostic value in NT-proBNP levels
      between obese children and healthy controls.

PMID- 22145464
TI  - Multivariate analyses of factors that affect neonatal screening thyroid
      stimulating hormone.
AB  - AIMS: All screening programmes in the UK use a primary thyroid stimulating
      hormone (TSH) screen for congenital hypothyroidism. Recent attention has been
      paid to aspects of screening, such as the relation between blood spot TSH levels
      and birth weight or gestational age. The aim of our study was to determine the
      factors affecting screening neonatal TSH levels. METHODS: We conducted a
      retrospective analysis of blood spot screening TSH levels of all infants screened
      at a single regional screening laboratory. RESULTS: There were 6498 infants
      screened during a 12-week period. Screening TSH level showed negative correlation
      with gestational age and birth weight. Multiple linear regression analysis
      revealed low birth weight as the only independent factor affecting screening TSH
      level. CONCLUSIONS: Low birth weight infants appear to be at risk of thyroidal
      dysfunction. Our study showed that there were clinically significant but weak
      correlation between higher screening TSH levels and low birth weight. The
      clinical importance of these findings requires larger prospective studies to
      further elucidate the relevance of these factors affecting TSH screening levels.

PMID- 22145465
TI  - Establishment of reference range of plasma amino acids for younger Chinese
      children by reverse phase HPLC.
AB  - BACKGROUND: Due to lack of country-specific norms in China, we established the
      reference range of plasma amino acids for younger Chinese children by reverse
      phase high-performance liquid chromatography (HPLC). METHODS: Plasma proteins
      were precipitated with ethanol. L-Norvaline served as an internal standard. This
      HPLC method was based on automated precolumn derivatization using o
      phthalaldehyde 3-mercaptopropionic acid for primary amino acids and 9
      fluorenylmethyl chloroformate for secondary amino acids. Twenty-three amino acid
      derivatives were separated by a Zorbax Eclipse AAA column and detected
      fluorometrically. Plasma amino acids were measured in 108 healthy Chinese
      children (ages 0-5 years, 59 boys and 49 girls). RESULTS: The assay was linear
      from 7.2 to 925.0 micromol/L for all amino acids. Recovery of amino acids added
      to plasma samples was 93%-107%. Within- and between-run reproducibility was 0.18%
      6.27% and 2.94%-16.15%, respectively. Sex- and age-specific plasma amino acid
      reference range for younger Chinese children was established. In our study, the
      boys had significantly higher levels of glutamine, citrulline, and tryptophan
      than girls (p < 0.05), and the girls had a significantly higher level of alanine
      than boys (p < 0.05). Compared with the 0- to 1-year group, the 1- to 5-year
      group had significantly higher levels of citrulline, valine, phenylalanine,
      isoleucine, and sarcosine and lower levels of aspartate, glutamate, serine,
      threonine, alanine, methionine, and tryptophan (p < 0.05). CONCLUSIONS: This
      study validates the HPLC method described here as a simple, rapid, and reliable
      assay. The reference range of plasma amino acids for younger Chinese children is
      different from that for Caucasian children and will facilitate our clinical
      diagnosis in the future.

PMID- 22145466
TI  - Differentiated thyroid carcinomas in childhood: clinicopathologic results of 26
      patients.
AB  - Epithelial solid tumors which are rare in childhood are responsible for about 9%
      of all childhood cancers. However, differentiated thyroid carcinomas (DTCs) are
      the most common of the endocrine neoplasia (0.5%-3%) in all childhood
      malignancies. Pediatric thyroid cancers have some clinicopathological differences
      from adult thyroid cancers. This analysis investigates the clinical behavior and
      pathological characteristics of childhood thyroid cancers, with treatment options
      and outcomes. A total of 26 patients who had been diagnosed as having
      differentiated thyroid cancer when they were younger than 18 years old, and who
      took radioiodine ablation treatment, were included in this analysis. The
      incidence of multifocality, capsule invasion and lymph node metastasis were
      calculated as 11.5%, 42.3% and 53.8%, respectively. At the 6th month, an absence
      of I-131 uptake in the neck, with a serum thyroglobulin (Tg) level < 1 ng/mL in
      the T4 off state, was accepted as the criterion for ablation of thyroid remnant.
      The mean follow-up period was 20.4 months (range 6 months-5 years). As a result,
      19 patients were ablated with a single dose of I-131 (2-4 GBq). A total of 6
      patients took a second dose of radioiodine treatment for lymph node or distant
      metastases. One of these patients was 6 years old and had recently received
      ablation. He had diffuse lung metastasis, which was detected on the 6th day post
      ablation with whole body scintigraphy, and he is now under follow-up. Successful
      surgery and an effective radioiodine ablation have a crucial role in good
      outcomes of childhood DTCs.

PMID- 22145467
TI  - Differentiated thyroid carcinoma: presentation and follow-up in children and
      adolescents.
AB  - To review our Pediatric Endocrinology Division's experience with differentiated
      thyroid carcinoma (DTC) we analyzed retrospectively the records of patients with
      DTC that had been seen between June 1988 and June 2008. RESULTS: Forty-five
      patients (median age 13.7 years, 36 female) were diagnosed (papillary: 40,
      follicular: 5) with DTC presenting as a solitary nodule (n: 25), thyroid nodule
      with cervical adenopathy (n: 9) and multinodular goiter (n: 11). All underwent
      total thyroidectomy with resection of suspicious cervical lymph nodes (CLN). DTC
      was multicentric in 59% and revealed extrathyroidal extension in 44%. Initially,
      44% had CLN metastases and 24% distant metastases. All patients underwent thyroid
      remnant ablation with 131I and suppressive treatment. Median follow-up was 5.1
      years with a disease-free survival rate at 5 years of follow-up of 75%. Eleven
      percent presented recurrences. CONCLUSION: Pediatric DTC has an aggressive
      behavior at presentation. Higher preoperative TSH levels were significantly
      associated with a more advanced disease at diagnosis. CLT was present
      concomitantly in a quarter of the patients and further studies are needed to
      establish differences in these patients' outcome. Diagnostic approach, total
      thyroidectomy, 131I treatment and thyrotropin suppression allowed a good
      progression-free survival rate.

PMID- 22145468
TI  - Two cases of Fanconi-Bickel syndrome: first report from China with novel
      mutations of SLC2A2 gene.
AB  - Fanconi-Bickel syndrome (FBS) is a rare inherited disease caused by mutations in
      the glucose transporter 2 gene, SLC2A2. We reported the first two Chinese cases
      of FBS. Both cases presented typical clinical features of hepatomegaly,
      hypophosphatemic rickets, severely stunted growth, fasting hypoglycemia along
      with postprandial hyperglycemia, and proximal renal tubular dysfunction with
      disproportionately severe glucosuria. Genetic analysis of SLC2A2 gene revealed
      novel compound heterozygous mutations in both patients. The characteristics of
      being born as small for gestational age and apparent liver dysfunction in our
      cases have been seldom discussed in the literature. It seems FBS patients in
      general have lower birth weight than normal, but further data collection is still
      needed. Symptomatic treatments were effective, but the serum transaminase of
      patient 2 remained moderately increased, and he patient needed further follow-up.
      The present study will supplement the up-to-date clinical characteristic spectrum
      for FBS.

PMID- 22145469
TI  - Idiopathic Fanconi's syndrome with nephrogenic diabetes insipidus in a child who
      presented as vitamin D resistant rickets--a case report and review of literature.
AB  - Fanconi's syndrome is a complex of multiple tubular dysfunctions of proximal
      tubular cells occurring alone or in association with a variety of inherited
      (primary) or acquired (secondary) disorders. It is characterized by
      aminoaciduria, normoglycemic glycosuria, tubular proteinuria without hematuria,
      metabolic acidosis without anion gap and excessive urinary excretion of
      phosphorous, calcium, uric acid, bicarbonate, sodium, potassium and magnesium.
      Diabetes insipidus is a disease of collecting tubules and a child mainly presents
      with dehydration and hypernatremia. We report the first case of idiopathic
      Fanconi's syndrome along with nephrogenic diabetes insipidus (NDI) in a child who
      presented to us as resistant rickets. Medline search did not reveal any case of
      nephrogenic diabetes insipidus associated with idiopathic Fanconi's syndrome. We
      hypothesized that the NDI may be due to severe hypokalemia induced tubular
      dysfunction. The child was treated for hypophosphatemic rickets with severe
      metabolic acidosis and the treatment for NDI was also given. Now he has healed
      rickets and normal blood pH, sodium and osmolarity.

PMID- 22145470
TI  - U.S. News and World Report's rankings of the top 50 children's hospitals for
      diabetes and endocrinology reflect reputation more than objective measures.
AB  - The objective of this short communication was to evaluate the roles of reputation
      and objective measures in U.S. News rankings of the top 50 children's hospitals
      for diabetes and endocrinology. Analysis was performed on data obtained from the
      2011 to 2012 report. Reputation scores exhibited more variance (CV = 158%)
      compared to objective measures (average CV = 14%). Ranking hospitals based on
      reputation, compared to total score, identified the same top hospital, same top
      five hospitals, and 90% of the same top 10 hospitals. Ranking based on total
      objective score resulted in different top hospitals, 60% of the same top five
      hospitals, and 50% of the same top 10 hospitals. Hospital total rank was strongly
      associated with reputation rank (rho2 = 0.78) and moderately associated with
      objective rank (rho2 = 0.48). Objective rank was minimally associated with
      reputation rank (rho2 = 0.19). Among the top 50 children's hospitals in diabetes
      and endocrinology, standings reflect reputation more than objective measures.

PMID- 22145471
TI  - AV59M KCNJ11 gene mutation leading to intermediate DEND syndrome in a Chinese
      child.
AB  - Heterozygous activating mutations in the KCNJ11 gene can cause permanent and
      transient neonatal diabetes. In the present study, we sequenced the KCNJ11 gene
      in a Chinese boy diagnosed with permanent neonatal diabetes mellitus (PNDM) and
      also in his parents. A heterozygous 175G > A (V59M) mutation was identified in
      the patient, while no KCNJ11 gene mutations were found in his parents, indicating
      that this mutation is de novo. The patient with the V59M mutation successfully
      switched from insulin injections to oral glibenclamide; 2 years of follow-up
      revealed that the patient had intermediate developmental delay, epilepsy and
      neonatal diabetes (DEND) syndrome. This is the first patient who is reported to
      have iDEND syndrome due to KCNJ11 V59M mutation in China.

PMID- 22145472
TI  - Congenital hypopituitarism presenting as dilated cardiomyopathy in a child.
AB  - Congenital hypopituitarism is commonly diagnosed either in infancy with neonatal
      hypoglycemia, prolonged jaundice and/or microphallus or in early to mid-childhood
      because of short stature. Replacement of deficient hormones allows the affected
      children to have a normal and productive life. We describe a 10-year-old boy with
      congenital hypopituitarism whose parents first sought definitive medical
      attention when the child developed congestive heart failure due to dilated
      cardiomyopathy, presumably secondary to prolonged untreated central
      hypothyroidism and growth hormone deficiency.

PMID- 22145473
TI  - Seventeen-year-old adolescent with pituitary abscess.
AB  - Pituitary abscess is a rare but potentially life-threatening infectious process.
      Diagnosis is challenging as symptoms are non-specific and signs of infection may
      be absent. We report the case of a previously healthy 17-year-old male who
      presented with worsening headaches, polyuria, polydipsia and no clinical signs of
      infection. On evaluation, he was found to have hypopituitarism with diabetes
      insipidus, hypothyroidism and adrenal insufficiency. An imaging study revealed a
      pituitary mass. He underwent transsphenoidal biopsy to rule out tumor. The
      abscess was drained transsphenoidally and he was treated with parental
      antibiotics. Magnetic resonance imaging one year later revealed a normal
      pituitary without any evidence of abscess or mass. He continues to require
      thyroid, adrenal and anti-diuretic hormone replacements. As with any pituitary
      lesion, prompt complete hypothalamic pituitary evaluation is essential to avoid
      potentially life-threatening consequences.

PMID- 22145474
TI  - Blastomycosis of the central nervous system in a child: a rare cause of
      hypopituitarism.
AB  - Blastomyces dermatitidis is a dimorphic fungus that can cause granulomatous
      lesions. Typically, children present with respiratory symptoms. Central nervous
      system involvement is unusual, and almost always associated with involvement of
      other organs. This case report, to our knowledge, is the first published case of
      an adolescent male presenting with panhypopituitarism secondary to a
      blastomycosis infection.

PMID- 22145475
TI  - A novel homozygous HESX1 mutation causes panhypopituitarism without midline
      defects and optic nerve anomalies.
AB  - OBJECTIVE: There are many genes reported to have been associated with combined
      pituitary hormone deficiencies, but mutations in HESX1 strongly correlate with
      septo-optic dysplasia. Our aim was to determine the cause of panhypopituitarism
      in our patient. PATIENTS AND METHODS: We studied an 8-month-old child having
      panhypopituitarism. The coding exons of PIT1, PROP1, LHX3, and HESX1 genes were
      amplified. Direct sequencing was done after denaturing HLPC. RESULTS: We
      identified a novel homozygous mutation (R160H) within the homeodomain of HESX1,
      which, to our knowledge, is the first to be described in humans. Neuroimaging
      studies revealed anterior pituitary aplasia, a normal posterior pituitary gland,
      and a thin pituitary stalk but no midline abnormalities. Optic nerve studies
      showed no pathology. This mutation is also carried in the parents of the affected
      child in a heterozygous pattern, suggesting an autosomal recessive inheritance.
      CONCLUSION: These data demonstrate that homozygous HESX1 mutation causing an
      R160H substitution can result in panhypopituitarism without midline defects.

PMID- 22145476
TI  - Poorly differentiated thyroid carcinoma in a 9-year-old boy: case report.
AB  - Poorly differentiated thyroid carcinoma (PDTC) is a rare disease with a poor
      prognosis in children. We describe a 9-year-old boy with a thyroid nodule
      composed of cystic and solid components, which became completely solid and
      hypoechoic and was subsequently proved to be PDTC. The tumor consisted of small-
      to intermediate-size round cells in a trabecular or insular pattern with
      hyperchromatic nuclei and mitotic figures. The tumor cells were positive for
      thyroid transcription factor 1 and thyroglobulin. PDTC is morphologically and
      prognostically between the well-differentiated and anaplastic carcinomas. It must
      be distinguished from the solid variant of papillary carcinoma and well
      differentiated follicular carcinoma with a predominantly solid/trabecular growth
      pattern. The tumor stage was T2N0M0. The patient was treated with total
      thyroidectomy, left-sided neck level VI lymph node dissection, recombinant human
      thyrotropin-stimulated 131I ablation therapy, and thyroid-stimulating hormone
      suppression. Malignancy should be suspected in a cystic thyroid nodule that
      becomes solid and hypoechoic.

PMID- 22145477
TI  - Congenital hypothyroidism in association with chromosome 3p25.3-pter deletion.
AB  - This report describes a case of a neonate presenting with many of the typical
      phenotypic characteristics of chromosome 3p deletion including hypertelorism,
      flat nasal bridge, flat philtrum, thin lips and low-set ears. The hands and feet
      showed post axial polydactyly, single palmar creases and rocker bottom feet. A
      karyotype confirmed chromosome 3p25.3-pter deletion with normal parental
      karyotypes. A high TSH was noted on newborn screening and congenital
      hypothyroidism was confirmed on thyroid function tests. Thyroid nuclear imaging
      was suggestive of dyshormonogenesis. This is the first reported case of
      congenital hypothyroidism in an infant with chromosome 3p deletion.

PMID- 22145478
TI  - Membranoproliferative glomerulonephritis associated with autoimmune thyroiditis.
AB  - We present a rare case of membranoproliferative glomerulonephritis (MPGN)
      associated with autoimmune hypothyroidism in a child. The exact pathogenesis of
      glomerulonephritis remains unclear. Thyroxine replacement therapy along with
      steroids may lead to significant decrease in proteinuria and resolution of edema.
      Thyroid status should be evaluated in all cases with MPGN.

PMID- 22145479
TI  - Report of two unrelated patients with hereditary vitamin D resistant rickets due
      to the same novel mutation in the vitamin D receptor.
AB  - BACKGROUND/AIMS: Two unrelated patients found to have hereditary vitamin D
      resistant rickets (HVDRR) were admitted to our hospital. METHODS: This article
      describes the diagnosis, management and molecular basis for their disease.
      RESULTS: Both patients had severe growth and motor developmental retardation,
      rickets with chest deformities and pulmonary abnormalities, but no alopecia. Both
      had hypocalcemia, secondary hyperparathyroidism and susceptibility to pulmonary
      infections. In both cases, good response with normalization of abnormal
      biochemistries and healing of rickets was achieved with IV calcium infusion.
      Subsequently, improvement was maintained with oral calcium. Both children
      harbored the same unique missense mutation in the vitamin D receptor (VDR) gene
      that substituted arginine with histidine at amino acid 274 (R274H) in the VDR
      ligand-binding domain (LBD). R274 is a contact point for the 1alpha-hydroxyl
      group of 1,25(OH)2D3, the active ligand for the VDR. Functional analyses of the
      R274H mutation revealed a 100-fold decrease in activity compared to wild-type
      VDR. CONCLUSION: We describe a novel missense mutation at R274H in the VDR gene
      that resulted in the HVDRR syndrome in two unrelated children. Vigorous treatment
      using IV calcium to normalize their hypocalcemia achieved dramatic improvement in
      these complex and severely ill patients.

PMID- 22145480
TI  - Vitamin D dependent rickets, diagnostic and therapeutic difficulties: two case
      reports.
AB  - There are two types of vitamin D dependent rickets (VDDR) that cause rickets in
      children. Vitamin D dependent rickets type 1 (VDDR-I) is caused by an inborn
      error of vitamin D metabolism, which interferes with renal conversion of
      calcidiol (25OHD) to calcitriol (1,25(OH)2D) by the enzyme 1alpha-hydroxylase.
      Vitamin D dependent rickets type 2 (VDDR-II) is caused by a defect in the vitamin
      D receptor (VDR). We report cases of two African children affected by VDDR-I and
      VDDR-II, respectively. Establishing an early diagnosis of these genetic forms of
      rickets is challenging, especially in developing countries where nutritional
      rickets (NR) is the most common variety of the disease. A prompt diagnosis is
      necessary to initiate adequate treatment, resolve biochemical features and
      prevent complications, such as severe deformities that may require surgical
      intervention.

PMID- 22145481
TI  - A novel AVPR2 missense mutation in a Chinese boy with severe inherited
      nephrogenic diabetes insipidus.
AB  - Inherited nephrogenic diabetes insipidus (NDI) is characterized by renal
      resistance to arginine vasopressin (AVP). The most common cause is mutations in
      the AVP receptor 2 (AVPR2) gene at Xq28. Severe complications of NDI are rare but
      can occur after severe dehydration without treatment. A 7-year-old boy presented
      with short stature and severe intellectual disability other than polyuria and
      polydipsia. The karyotype was normal. Direct sequencing revealed a novel missense
      mutation c.506T > C (p.L169P) in AVPR2 in the patient. His mother was
      heterozygous for the mutation. The mutation was absent in 103 unrelated healthy
      males and predicted to be consistently pathogenic by several prediction methods,
      including Polyphen, SIFT, PMut, PhD-SNP, SNPs3D, PANTHER, and MEMPACK. Awareness
      of the primary signs of NDI, polyuria, and polydipsia would facilitate early
      diagnosis and treatment to prevent its severe complications. Also, molecular
      analysis will provide a rapid and definitive diagnosis and facilitate genetic
      counseling for family planning.

PMID- 22145482
TI  - From idiopathic diabetes insipidus to neurodegenerative Langerhans cell
      histiocytosis--an unusual presentation and progression of disease.
AB  - Diabetes insipidus (DI) is rare in childhood and has a wide-ranging aetiology
      including the involvement of uncontrolled proliferation of dendritic cells in the
      hypothalamic-pituitary axis, characteristic of Langerhans cell histiocytosis
      (LCH). DI may manifest as a sequela of multisystem LCH disease involving skin,
      bone, liver, spleen and lymph nodes. In very rare cases patients diagnosed with
      LCH exhibit neurodegenerative changes, such as severe ataxia, tremor, dysarthria
      and intellectual impairment. We report a 2 1/2-year-old boy who presented
      initially with apparent idiopathic DI, developed anterior pituitary hormone
      deficiency and progressive neurological deterioration secondary to
      neurodegenerative LCH.

PMID- 22145483
TI  - Unique concurrent appearance of two rare conditions in a young girl: central
      precocious puberty due to hypothalamic hamartoma and uncommon type of diabetes.
AB  - Hypothalamic hamartomas (HH) are rare congenital nonneoplastic lesions of the
      tuber cinereum, which usually present as precocious puberty of central origin in
      young girls and respond well to treatment with long acting gonadotropin releasing
      hormone (GnRH) analogs. No association of this condition with diabetes mellitus
      of any form has been reported so far. On the other hand, diabetes mellitus in
      children and adolescents, when it is not autoimmune type 1 diabetes, is difficult
      to classify. We present a girl with early onset of central precocious puberty at
      the age of 8 months, due to hypothalamic hamartoma. Treatment with depot of a
      GnRH analog for a period of 9 years and 8 months was successful, and her puberty
      continued 6 months after the discontinuation of triptorelin. At the age of 9
      years 6 months, the girl presented with diabetes. She was negative for islet, GAD
      and IA2 antibodies and her insulinemia and C-peptide remained within normal
      limits during the 2 years of follow-up. Her metabolic control is excellent with a
      combination of metformin and a low-dose of mixed insulin. To our knowledge, this
      is the first description of the simultaneous appearance of these two
      endocrinological conditions.

PMID- 22145484
TI  - Hyperinsulinism associated with gestational exposure to bupropion in a newborn
      infant.
AB  - This case report describes severe hyperinsulinism in a term newborn infant
      without typical perinatal risk factors for transient hyperinsulinism. The mother
      had received bupropion, an antidepressant and aid to smoking cessation,
      throughout pregnancy. The infant presented with profound hypoglycemia and
      seizures on the 3rd day of life. Laboratory investigation confirmed
      hyperinsulinism. Stable euglycemia could be achieved only after starting
      diazoxide. The infant was weaned from diazoxide by 10 weeks of age without
      recurrence of hypoglycemia, signifying the transient nature of hyperinsulinism.
      This is the first reported case of a potential association between maternal
      bupropion use during pregnancy and neonatal hyperinsulinism, and highlights the
      importance of close monitoring of similar infants.

PMID- 22145485
TI  - Child abuse suspicion masquerading new onset insulin dependent diabetes mellitus.
AB  - The identification and diagnosis of child abuse is a challenging task to the
      pediatrician. The increased awareness among both the public and medical
      personnel, while improving attentiveness to this important subject, can sometimes
      result in misdiagnosing medical conditions, thus causing distress and delay in
      required treatment. Numerous reports have described conditions mimicking non
      accidental injuries; most of these include dermatological findings related to
      skin diseases, medical conditions causing pathological fractures, and rare
      diseases with unusual physical findings. We present a case of a 9.5-year-old
      child in which the workup for a suspected abusive event led to a delay in the
      diagnosis of insulin dependent diabetes mellitus later presented as diabetic
      ketoacidosis.

PMID- 22145486
TI  - Identification of two novel BCKDHA mutations in a Chinese patient with maple
      syrup urine disease.
AB  - Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder
      affecting branched-chain amino acids. Mutations in the BCKDHA, BCKDHB, and DBT
      gene impair the branched-chain alpha-ketoacid dehydrogenase (BCKD) complex,
      resulting in the accumulation of branched-chain amino acids and branched-chain
      alpha-ketoacid in tissues and plasma. This leads to mental and physical
      retardation, feeding problems, and a maple syrup odor in the urine. In this
      study, we describe the clinical and biochemical manifestations of a sporadic
      mutation in a neonate with classic MSUD. Analysis of the BCKDHA gene revealed a
      compound heterozygous mutation consisting of two novel missense mutations
      (p.L103P and p.R265P). Viewing the protein with PyMOL indicated that the p.L103P
      and p.R265P mutations were, respectively, located in the helical region and core
      domains of the BCKD's Ela component. The p.L103P mutation affected the
      hydrophobic cores and is predicted to shorten the helix; the p.R265P mutation can
      predictably affect the cofactor binding site by ligating the associated manganese
      ion. In conclusion, we identified two novel missense mutations in the BCKDHA gene
      in a Chinese patient with MSUD.

PMID- 22145487
TI  - Unexpected finding of an intact distal vagina in an infant with mixed gonadal
      dysgenesis.
AB  - Mixed gonadal dysgenesis (MGD) is a form of sex chromosome disorder of sex
      development with large phenotypic variability. Patients with MGD typically have
      asymmetric and ambiguous genitalia with a combination of Mullerian and Wolffian
      duct derivatives. Prenatal androgen exposure results in variable degrees of
      phallic enlargement and a urogenital sinus. Here, we report an infant with
      ambiguous genitalia due to MGD. Despite marked evidence of prenatal androgen
      exposure, there was a completely intact distal vagina.

PMID- 22145488
TI  - Acrogigantism and facial asymmetry: McCune-Albright syndrome.
AB  - McCune-Albright syndrome (MAS) is characterized by a triad of poly/monoostotic
      fibrous dysplasia, cafe-au-lait macules and hyperfunctioning endocrinopathies.
      Association of MAS with GH excess is rare, and in most of the instances
      somatotropinoma has not been documented. Treatment of patients of MAS with
      acromegaly is difficult because of thickened calvarium and dysplastic skull bone.
      We report a 17-year-old girl, who presented with cranio-facial fibrous dysplasia,
      cafe-au-lait macules and also had acromegaly due to pituitary macroadenoma, and
      treated with gamma knife radiosurgery.

PMID- 22145489
TI  - Surgical enucleation of testicular leydigioma in a young child: case report and
      literature review.
AB  - BACKGROUND: The leydigioma is the most frequent interstitial neoplasm of the
      testis. Clinical symptoms of all leydigioma usually are isosexual precocious
      pseudo-puberty due to autonomous testosterone overproduction, suppressed
      gonadotropin levels and a testis mass. Nowadays its therapy is debated. DESIGN
      AND METHODS: We report a case of a young child treated in 2008 for a leydigioma
      of the testis with atypical clinical behavior. Testicular oncologic markers and
      hormonal profile were assessed. RESULTS: The patient was treated successfully
      with organ-confined surgery. CONCLUSION: We want to confirm the safety of
      conservative surgery against radical orchiectomy and review the literature of the
      last decade on this debated matter.

PMID- 22145490
TI  - A rare case of severe lactic acidosis in a preterm infant: lack of thiamine
      during total parenteral nutrition.
AB  - Total parenteral nutrition (TPN) is a revolution in neonatal intensive care unit
      (NICU) care, but this therapy is not without problems. A 35-week-old, 1300 g
      female infant was transferred to our NICU because of bilious vomiting and feeding
      problems. When enteral feeding was started again, a severe condition similar to
      the previous one developed. On the 24th day, the patient underwent surgery with a
      diagnosis of Hirschprung's disease. One week before surgery, the parenteral
      solutions were composed without vitamins because intravenous vitamin supplements
      suitable for infants were not available. Thereafter, the patient suffered from
      severe hypoglycaemia, and sepsis started to develop, accompanied by a large anion
      gap and metabolic acidosis which is severe lactic acidosis refractory to massive
      doses of bicarbonate. The acidosis improved significantly when the patient was
      treated with thiamin. Although TPN is life saving in the NICU, meticulous
      attention must be paid while treating a patient with TPN, and all possible
      nutrients should be provided. In this report, a case of a preterm newborn
      requiring a prolonged period of TPN and complicated by serious lactic acidosis is
      presented and discussed.

PMID- 22145491
TI  - Autoimmune polyendocrinopathy associated with ring chromosome 18.
AB  - Phenotypic and clinical features of individuals with ring chromosome 18 [r(18)]
      vary with the extent of deletion of the short (18p-) or long arm (18q-). Most
      patients with r(18), therefore, demonstrate a clinical spectrum of both 18p- and
      18q- deletions. Short stature, microcephaly, mental and motor retardation,
      craniofacial dysmorphism and extremity abnormalities are the most commonly
      reported features in patients with r(18). Abnormalities of chromosome 18,
      especially 18p- syndrome, are often reported with autoimmune thyroid disease and
      growth hormone deficiency, but reports of endocrine abnormalities associated with
      r(18) are rare. Here, we report a case of an African-American female with
      hyperthyroidism, type 1 diabetes mellitus, vitiligo and IgA deficiency associated
      with a r(18) chromosome complement. This patient additionally had mild
      intellectual disability and dysmorphic features. Karyotype analysis showed a de
      novo ring chromosome 18 (deletion 18q23-18qter and deletion 18p11.3-18pter).
      Although this unique association of autoimmune polyglandular endocrinopathy with
      ring chromosome 18 could be coincidental, we speculate that a gene or genes on
      chromosome 18 might play a role in the autoimmune process.

PMID- 22145492
TI  - SADDAN syndrome.
AB  - Achondroplasia is the most common type of short-limbed dwarfism in children
      resulting from fibroblast growth factor receptor (FGFR) mutations. Activating
      mutations of FGFR3 also result in other forms of skeletal dysplasia and
      craniosynostosis. Acanthosis nigricans is associated with these skeletal
      dysplasias and we recently encountered a skeletal dysplasia along with acanthosis
      nigricans in a young boy. We report the case due its unusual nature affecting one
      of twin brothers.

PMID- 22145493
TI  - Primary adrenal insufficiency in a child after busulfan and cyclophosphamide
      based conditioning for hematopoietic stem cell transplantation.
AB  - High rates of skeletal complications, growth disturbances, thyroid and gonadal
      dysfunction have been described in children undergoing stem cell transplantation.
      Although secondary adrenal insufficiency has been diagnosed, no primary adrenal
      insufficiency has been reported after busulfan and cyclophosphamide (Bu/Cy)-based
      conditioning regimens for stem cell transplantation in children. A 9-year-old
      girl with myelodysplastic syndrome was treated with stem cell transplantation of
      allogeneic origin. She received myeloablative conditioning chemotherapy, Bu and
      Cy. Her serum cortisol level was normal before stem cell transplantation. Then,
      17 months after stem cell transplantation, chronic graft-versus-host disease
      developed and was treated with methyl prednisolone for 3 months. The control
      endocrinological investigation revealed low serum cortisol and high serum
      adrenocorticotropin (ACTH) levels 6 months after completion of methyl
      prednisolone treatment. The ACTH stimulation test demonstrated primary adrenal
      insufficiency, and the other etiologies of primary adrenal insufficiency were
      excluded. The patient received oral prednisolone replacement therapy. She was
      followed-up for 44 months and required increases in steroid doses during stress
      periods. Primary adrenal insufficiency which was observed in our patient after
      Bu/Cy-based conditioning regimen for stem cell transplantation has not been
      reported in children and adrenal function should be closely monitored in these
      patients both before stem cell transplantation and after stem cell
      transplantation.

PMID- 22145494
TI  - Maple syrup urine disease in mainland China.

PMID- 22145495
TI  - Evidence does not support the conclusion that soy is an endocrine disruptor.

PMID- 22145496
TI  - Medical iodophobia is contagious.

PMID- 22145497
TI  - Births: final data for 2008.
AB  - OBJECTIVES: This report presents 2008 data on U.S. births according to a wide
      variety of characteristics. Data are presented for maternal demographic
      characteristics including age, live-birth order, race and Hispanic origin,
      marital status, attendant at birth, method of delivery, and infant
      characteristics (period of gestation, birthweight, and multiple births). Birth
      and fertility rates by age, live-birth order, race and Hispanic origin, and
      marital status also are presented. Selected data by mother's state of residence
      are shown, as well as data on age of father. Trends in fertility patterns and
      maternal and infant characteristics are described and interpreted. METHODS:
      Descriptive tabulations of data reported on the birth certificates of the 4.25
      million births that occurred in 2008 are presented. Denominators for population
      based rates are postcensal estimates derived from the U.S. 2000 census. RESULTS:
      A total of 4,247,694 births were registered in the United States in 2008, 2
      percent less than in 2007. The general fertility rate declined 1 percent to 68.6
      per 1,000. The teenage birth rate declined 2 percent to 41.5 per 1,000. Birth
      rates for women aged 20 to 39 years were down 1-3 percent, whereas the birth rate
      for women aged 40-44 rose to the highest level reported in more than 40 years.
      The total fertility rate declined 2 percent to 2,084.5 per 1,000 women. All
      measures of unmarried childbearing reached record levels-40.6 percent of births
      were to unmarried women in 2008. The cesarean delivery rate rose again to 32.3
      percent. The preterm birth rate declined for the second consecutive year to 12.3
      percent; the low birthweight rate was down very slightly. The twin birth rate
      increased 1 percent to 32.6 per 1,000; the triplet and higher-order multiple
      birth rate was stable.

PMID- 22145498
TI  - Outcomes of pregnancy complicated by heart disease at Maharaj Nakorn Chiang Mai
      Hospital.
AB  - OBJECTIVE: To determine pregnancy outcomes of women complicated by heart disease.
      MATERIAL AND METHOD: Pregnant women complicated with heart disease between
      January 1993 and December 2007, at Maharaj Nakorn Chiang Mai Hospital, were
      recruited to a retrospective cohort study. The normal controls were identified to
      match the cases with a ratio of 2:1. The main outcomes for comparison included
      fetal mortality and morbidity focusing on preterm birth and fetal growth
      restriction. RESULTS: One hundred twenty five pregnant women with heart disease
      and 250 controls were recruited. Rheumatic heart disease was more common than
      congenital heart disease (48.8% and 44.8%). The baseline characteristics were
      similar between both groups. The prevalence of operative vaginal delivery was
      significantly higher in the study group (32.8% and 4.4%, p < 0.001) while the
      cesarean section rate was similar. The prevalence of fetal death, low Apgar
      score, preterm births, fetuses with low birth weight, and fetal growth
      restriction and were significantly higher in the study group with a relative risk
      of 6.0, 3.0, 2.2, 1.92, and 1.8, respectively. CONCLUSION: Rheumatic heart
      disease is still prevalent. The fetal outcomes especially fetal death, preterm
      birth, intrauterine fetal growth restriction, low birth weight, and birth
      asphyxia were more common among pregnancies complicated by heart disease.

PMID- 22145499
TI  - Pain control in laparoscopic gynecologic surgery with/without preoperative
      (preemptive) parecoxib sodium injection: a randomized study.
AB  - OBJECTIVE: To determine the effectiveness of preoperative parecoxib sodium
      injection for pain relief after laparoscopic gynecologic surgery. MATERIAL AND
      METHOD: A prospective double-blind, randomized study was conducted in 268
      patients who underwent laparoscopic gynecologic surgery at Vajira Hospital
      between November 1, 2010 and March 31, 2011. The patients were randomly allocated
      into two groups to receive either single intravenous 40 mg parecoxib (treatment
      group; n = 133) or normal saline (control group; n = 135) 30 min before surgery.
      The degree of postoperative pain was assessed every 2 h in the first 8 h
      postoperation, then every 4 h until completion of 24 h by using a verbal rating
      scale. Total consumption of meperidine over a 24-h period and the adverse events
      relevant to parecoxib sodium were also recorded. RESULTS: Mean pain scores at all
      measured times in the treatment group were insignificantly lower than those in
      the control group (p = 0.106). The mean 24-h postoperative meperidine consumption
      in the treatment group was significantly lower compared to that in the control
      group (26.3 +/- 28.1 mg and 39.1 +/- 34.6 mg, respectively, p = 0.001). The
      proportion of patients requiring meperidine in the treatment group was
      significantly lower than that in the control group (58.6% and 70.3%,
      respectively, p = 0. 045). No serious adverse events were observed in both
      groups. CONCLUSION: Preoperative parecoxib sodium significantly reduced
      postoperative meperidine requirement and consumption, while insignificantly
      declined the pain scores. Serious adverse events were not encountered

PMID- 22145500
TI  - Postoperative color Doppler sonography of the ureteral jets to detect ureteral
      patency in laparoscopic hysterectomy.
AB  - OBJECTIVE: To assess the accuracy of color Doppler sonography of the ureteral
      jets in detecting ureteral injury for gynecologic patient who had undergone
      laparoscopic hysterectomy. MATERIAL AND METHOD: A prospective study was performed
      on 170 patients scheduled for laparoscopic hysterectomy. The operations were
      performed for benign gynecologic disease. All patients had pre-and post-operative
      color Doppler sonography of the ureteral jets to determine ureteral patency.
      Transabdominal color Doppler sonography was used to evaluate the presence or
      absence of the ureteral jets from both ureteric orifices. The time for detection
      of the first jet and the number of jets in five minutes were recorded separately
      for each side. Preoperative assessment was used as control. Statistical analysis
      was performed by using Wilcoxon signed ranks test, considering p < 0. 05 as
      significant. If there was absence of the ureteral jet on one or both sides, the
      patient was sent to repeat color Doppler sonography on the next day Intravenous
      pyelography was performed to confirm ureteral injuries when the repeat
      examination was still found abnormal. RESULTS: Bilateral ureteral jets were
      demonstrated by color Doppler sonography in 168 of the 170 patients. In two
      patients, postoperative examination demonstrated the absence of the ureteral jet
      on the left side. Intravenous pyelography was performed and confirmed left
      ureteral obstruction. They underwent left ureteroneocystostomy. In 168 patients,
      bilateral ureteral jets were demonstrated in either preoperative or postoperative
      examination. The time for detection of the first jet was not significantly
      different between preoperative and postoperative examination of either the right
      side (p = 0.189) or the left side (p = 0.694). The number of jets in five minutes
      was not significantly different between preoperative and postoperative
      examination of either the right side (p = 0.854) or the left side (p = 0.675).
      CONCLUSION: Color Doppler sonography is a simple and reliable technique that may
      be used to evaluate ureteral jets into the bladder in patients who underwent
      laparoscopic hysterectomy. The time for detection of the first jet and the number
      of jets in five minutes are not affected by the postoperative status. The
      presented test may be a good screening test to detect ureteral injuries following
      laparoscopic hysterectomy.

PMID- 22145501
TI  - Adherence to mineral and bone disorder clinical practice guidelines in chronic
      kidney disease.
AB  - BACKGROUND: Mineral and bone disorders (MBD) in patients with chronic kidney
      disease (CKD) are cardiovascular risk factors. Clinical practice guidelines were
      developed to prevent MBD and to decrease cardiovascular events in CKD patients.
      OBJECTIVE: To determine adherence to mineral and bone disorder clinical practice
      guidelines (MBD-CPG) in chronic kidney disease patients. MATERIAL AND METHOD: A
      retrospective, observational study was performed on 206 patients with CKD stage
      3, 4, and 5 that were followed-up at pre-dialysis and dialysis clinic, Nephrology
      Unit, Srinagarind Hospital between July and September 2007. RESULTS: The mean
      percentages of adherence in each patient were 89.5% for calcium monitoring, 88.6%
      for phosphate monitoring and 17.1% for PTH monitoring. The mean percentage of
      adherence to using of phosphate binder in each patient was 84.6%. The mean
      percentage of adherence to using of vitamin D3 was 72.2% in patients who had all
      three clinical parameters monitoring. The K/DOQI 2003 target recommendation
      achievements at the end of study were 73.7% for serum calcium, 76.1% for serum
      phosphate, 94.6% for calculated CaxP product, and 23.7% for serum PTH. The mean
      percentage of K/DOQI 2003 target recommendation achievement, in each patient
      during 12 months of postindex period, were: 79.3% for serum calcium, 78.1% for
      serum phosphate, 95.8% for serum CaxP product and 26.3% for serum PTH. The 100%
      achievement of target recommendations for serum calcium, serum phosphate and
      serum CaxP product were statistically, significant different, when compared
      between the group of 100% and 75.0-99.9% adherence to using phosphate binder,
      with the odd ratio 5.43 (95% CI 2.43-12.11) for serum calcium achievement, 11.33
      (95% CI 4.63-27.72) for serum phosphate achievement and 11.75 (95% CI 2.92-47.24)
      for CaxP product achievement. CONCLUSION: The use of vitamin D3, monitoring of
      serum PTH and achieving of PTH target level, are still far from recommendations.
      Therapeutic end point for cardiovascular and bone diseases should be investigated
      in long-term studies.

PMID- 22145502
TI  - Analysis of exon 8 of ATP7B gene in Thai patients with Wilson disease.
AB  - OBJECTIVE: Determine the frequency of mutations in exon 8 of ATP7B gene. MATERIAL
      AND METHOD: The exon 8 of ATP7B gene in twenty 20 unrelated Thai patients with
      Wilson disease (WD) was analyzed RESULTS: Three heterozygous mutations were
      identified in four patients. The Arg778Leu (G2333T) and 2299insC mutations have
      been previously reported. The authors also identified a novel missense mutation,
      Thr766Arg (C2297G). Despite the Arg778Leu mutation being common in East Asian
      populations, its frequency in Thais was only 5% in the presented patients.
      CONCLUSION: Sequencing of the exon 8 of the ATP7B gene is insufficient for the
      diagnostic service testing in Thais.

PMID- 22145503
TI  - Development of diabetes telephone-linked care system for self-management support
      and acceptability test among type 2 diabetic patients.
AB  - OBJECTIVE: Develop the diabetes telephone-linked care system for self-management
      support and test acceptability in terms of system uses, satisfaction and
      perception of easiness, helpfulness, and emotion with the system. MATERIAL AND
      METHOD: The automated telephone system with diabetes knowledge interactive voice
      response (IVR) subsystem was developed to provide diversified curriculum
      arrangement including general knowledge module (Knowledge IVR, suggestive segment
      module (Suggestive IVR) and 10 QA sets for assessment with tailored information
      feedback (QA IVR). The system could deliver 1,120 messages over five weeks among
      112 intervened participants of the on-going randomized controlled trial on its
      impact on glycemic control. The system analyzed the level of completed responses.
      RESULTS: Overall, 25.9% of the responses were intermittent, 46.4% had consistent
      adherences, 14.3% were poor responses, and 13.4% were non-responses. The total
      time use of the system, among 97/112 participants, was 6,189 minutes (mean 63.80,
      SD 26 63). The degree of call completeness did not vary according to the
      participant's socio-economic status, glycemic level, or years of diabetes
      diagnosis. The satisfaction of participants to the program was done by
      interviewed by telephone among 95 of 112 participants. Most study participants
      reported that they were very/moderately satisfied with the program (89.5%)
      regarding its usefulness and helpfulness on awareness, understanding and
      reminding behavior change attempts. In all, 95.8% of the responders planned to
      participate in the next program. Duration of time uses of the TLC was
      significantly correlated to the total scores of helpfulness and of emotion (p <
      0.01; r = 0.38 and 0.31 respectively). CONCLUSION: This prototype of diabetes
      telephone-linked care for Thai diabetes is a step forward in response to diabetes
      self-management education need. Further studies are needed about its efficacies
      on diabetes self-management improvement and glycemic control, as well as its cost
      effectiveness.

PMID- 22145505
TI  - Clinical outcome of children with primary distal renal tubular acidosis.
AB  - OBJECTIVE: To evaluate the clinical course of children with primary distal renal
      tubular acidosis and to determine parameters correlated with the outcomes.
      MATERIAL AND METHOD: A retrospective review of medical records was carried out.
      The parameters at initial diagnosis and the last visit were collected including
      height standard deviation score (SDS), weight SDS, ultrasonography of kidneys,
      serum electrolytes, urine electrolytes, urine calcium to urine creatinine ratio
      (urine Ca/Cr), serum creatinine, bicarbonate dosage and glomerular filtration
      rate estimated by Schwartz's formula (eGFR). RESULTS: Fifteen patients were
      included with median follow-up time of 12 years (range 4.5 to 19 years). Median
      age at diagnosis was 3 years (range 0.25 to 9 years). At the last visit, median
      height SDS increased significantly from -3.1 to -0.8 (p = 0.04). Height SDS at
      the last visit correlated with age at diagnosis (r = -0.54, p = 0.038) and serum
      bicarbonate at the last visit (r = 0.68, p = 0.008). Moreover, at the last visit,
      eGFR correlated with urine Ca/Cr (r = -0.84, p = 0.001). CONCLUSION: After
      treatment, growth of patients improved satisfactorily. The outcomes were
      associated with age at diagnosis, compliance of bicarbonate therapy and urine
      Ca/Cr at the last visit.

PMID- 22145504
TI  - Diagnostic value of two rapid immunochromatographic tests for suspected
      tuberculosis diagnosis in clinical practice.
AB  - OBJECTIVE: To evaluate and compare the diagnostic value of two
      immunochromatographic tests for tuberculosis (ICT-TB) in clinical practice.
      MATERIAL AND METHOD: The present extended cross-sectional study investigated
      suspected active TB patients at Maesai district hospital, and Lampang regional
      hospital between April 2009 and May 2010. Subjects underwent two commercial ICT
      TB serum tests including: an endogenous ICT-TB, a local made test coated with 38
      kD, 16 kD, and 6 kD antigens; and an exogenous ICT-TB, an imported test coated
      with 38 kD and lipoarabinomanan [LAM] antigens. All subjects received two months
      of follow up. RESULTS: Of 401 patients, 146 (36.4%) had active TB, and 206
      (51.4%) were HIVseropositive. An endogenous ICT-TB was superior to an exogenous
      ICT-TB in all diagnostic values measured except for specificity. In all patients,
      sensitivity was low, 35.6% (95% CI: 30.9-40.3) in an endogenous ICT-TB vs. 13.7%
      (95% CI: 10.3-17.1) in an exogenous ICT-TB. The specificity was high and
      equivalent in both tests, 93.7% (95%CI: 91.4-96.1). Higher diagnostic values were
      found among human immunodeficiency virus (HIV) seronegatives than in HIV
      seropositives when unadjusted for CD4+ cell count level. The likelihood ratios
      (LHR) were higher in patients with CD4+ cell count over 200 cells/microL than for
      the HIV seronegative group (LHR+ 7.6 vs. 4.8 in an endogenous ICT-TB, and 2.5 vs.
      1.9 in an exogenous ICT-TB). CONCLUSION: For the present study setting, an
      endogenous ICT-TB can be a meaningful tool for first-line testing to rule in TB
      suspected cases. Subgroups of HIV seronegative and HIV seropositive patients with
      CD4+ cell count over 200 cells/microL may be expected to benefit most from the
      test.

PMID- 22145506
TI  - Efficacy of portable vacuum dressing in chronic wound care: a prospective
      randomized control trial.
AB  - BACKGROUND: Chronic wound is a common clinical condition and often cause
      treatment problems. This is because chronic wound usually require extended
      treatment period, which result in high hospital cost. The treatment of chronic
      wound depends on the type of wound, the cause of wound, and the physical status
      of patient. Vacuum dressing has become a standard treatment of chronic wound.
      However in most hospitals, vacuum dressing is only used for in-patients thus,
      keeping the patients in hospital for this treatment. The problems with this are
      the long hospital stay, the high cost, and the unavailability of bed for other
      patients. This problem led us to develop a new treatment to help chronic wound
      patient. The potential solution was the use of a portable vacuum machine for out
      patient. If the efficacy of the portable vacuum machine was comparable to the
      wall vacuum then the benefit could be transferred to out-patient. MATERIAL AND
      METHOD: A Randomized control trial of two groups of patients, conventional vacuum
      dressing (n = 15) and portable vacuum dressing (n = 15), was done. Rate of wound
      healing was measured every three days and compared to represent efficacy between
      the two groups of patients. RESULTS: Thirty chronic wound patients were assigned
      randomly to a group of 15 for treatment with conventional wall vacuum dressing
      and another group of 15 for treatment with our portable vacuum dressing.
      Demographic data was similar in both groups (sex, age and underlying cause).
      Wound area was recorded at the start of the treatment on day 0 and recorded at
      day 3, 6, 9 and 12. It was then calculated into percentage of wound healing. Rate
      of wound healing was 1.57%/day in conventional group and 1.59%/day in portable
      group. There is no clinical difference between groups (p > 0.05). CONCLUSION: Our
      portable vacuum dressing method had no clinical difference from conventional wall
      vacuum dressing with respect to the rate of wound healing.

PMID- 22145507
TI  - Ultrastructural study of the detrusor in end stage renal disease.
AB  - BACKGROUND: After successful renal transplantation, almost 50% of the patients
      complained of lower urinary tract symptoms. There is no definite conclusion to
      explain these voiding symptoms and ultrastructural study of detrusor muscle in
      end stage renal disease (ESRD) has never been carried out before. OBJECTIVE: To
      study ultrastructural changes of detrusor muscle in the specific group of
      patients with end stage renal disease. MATERIAL AND METHOD: Detrusor biopsy of 20
      patients, including 15 in end stage renal disease and five in patients with
      normal creatinine, was obtained by open technique. Biopsy was done during
      ureteral reimplantation at the time of kidney transplantation. In normal renal
      function group, detrusor biopsy was done at the time of open bladder surgery from
      other urologic diseases. The specimens were processed for light microscopy and
      transmission electron microscopy using standard techniques. RESULTS: All
      specimens from open biopsy provided sufficient quality to be examined by electron
      microscope. The average creatinine level was 9.2 and 1.0 mg/dl in the ESRD group
      and control group, respectively In the ESRD group, all showed hypertrophy of
      muscle bundles, fibrosis between muscle bundles, muscle bundle degeneration, and
      fragmentation of muscle cells. In ESRD group, 93% had fibrosis around nerve
      bundles and enlarged muscle cell nuclei. About 60% had enlarged nerve bundles,
      and 53% showed amorphous inclusion in muscle cells. The ESRD group displayed many
      more ultrastructural changes than in the control group and some appearances were
      not present in the control group. CONCLUSION: There were distinct ultrastructural
      changes of detrusor muscles in ESRD patients. These ultrastructural changes of
      detrusor muscles may be associated with voiding dysfunction after kidney
      transplantation.

PMID- 22145508
TI  - Clinical study of a new design multifunction dynamic external fixator system for
      bone reconstructions.
AB  - BACKGROUND: Fractures with related problems including intercalary bone defect,
      shortening, and malunion are still major problems in orthopedic practice. The
      Ilizalov's circular external fixator device has several advantages for bone
      reconstruction but also has certain drawbacks such as its bulkiness and
      complicated mounting. To maintain the advantages of Ilizalov's original concept
      and combine with the simplicity of monolateral frame, a new design multifunction
      dynamic external fixator system was developed to overcome the drawbacks.
      OBJECTIVE: To evaluate the clinical results and complications of a new design
      multifunction dynamic external fixator system for bone reconstructions. MATERIAL
      AND METHOD: Twenty patients requiring reconstructions between 2006 and 2009
      participated in this study. The new design multifunction dynamic external
      fixators were used in 11 tibial and two femoral intercalary defects for bone
      transportation, three tibial and one femoral lengthening, and three tibial
      malunion correction (45, 60 and 75 degrees). RESULTS: In bone transportation, new
      bone formation and union at the docking site were achieved in all patients. The
      mean new bone formation was 5.8 cm (range 3.5-14) in tibia and 4.3 cm (range 3.5
      5) in femur. The mean healing index was 46.3 days/cm (range 42-60) in tibia and
      93.9 days/cm (range 85.7-102) in femur. In bone lengthening, new bone formation
      and union were achieved in all patients. The mean amount of elongation was 3.5 cm
      (range 3-4) in tibia and 5 cm in femur. The mean healing index was 71.1 days/cm
      (range 68.6-76) in tibia and 73 days/cm in femur. In malunion correction, the
      mean correction time was 65 days (range 35-84) and the mean healing time was
      187.3 days (range 154-212). CONCLUSION: The new design multifunction dynamic
      external fixator system was successfully used for bone transportation, bone
      lengthening, and malunion correction with good results and low complications. It
      is simple, safe, and easy to use.

PMID- 22145509
TI  - Factors of local recurrence of giant cell tumor of long bone after treatment:
      plain radiographs, pathology and surgical procedures.
AB  - BACKGROUND: To evaluate the relationship between local recurrence of giant cell
      tumor (GCT) after surgical treatments and plain radiography, pathology grade and
      surgical procedures. MATERIAL AND METHOD: Patients with pathologically proven
      primary giant cell tumor of long bones, who underwent surgical treatment in
      Siriraj Hospital between 1995 and 2007, were retrospectively reviewed. Plain
      radiographic findings were reviewed by an experienced musculoskeletal radiologist
      without knowledge of the clinical history or pathologic results. Specific
      attention on plain radiographic evaluations included site of tumor in long bone,
      total tumor volume, expansion of cortex, breaking of cortex, and presence of
      pathological fracture. Patients with grade III tumor were excluded due to
      malignant histology. Patients received treatments with amputation were also
      excluded due to no possibility of tumor recurrence. Only patients who received
      surgical treatments with wide excision or curettage with cement were included in
      the present study. Univariate analysis and Cox proportional hazard ratio was used
      to evaluate the influence of plain radiographic findings and histology grade on
      risk of tumor recurrence. RESULTS: Seventy-four patients participated in this
      study and included 32 males (43%) and 42 (57%) females with a mean age of 35
      years (range 17 to 84). The median follow-up time was 3.2 years. Forty-eight
      patients (65%) underwent curettage with cement or bone graft and 26 patients
      (35%) underwent wide excision. Sixty-three patients (85%) did not develop tumor
      recurrence while 11 patients (15%) developed local recurrent tumor. Those
      occurred only in patients who underwent curettage with cement or bone graft. None
      of the patients who underwent wide excision developed local recurrence. Median of
      time after operation to recurrence was 3.5 years (range, 0.5 to 10.3 years).
      Local recurrence occurred in the distal femur in five patients (45%), in the
      proximal tibia in five patients (45%), and in distal radius in one patient (9%).
      Risk of local recurrence of GCT was not statistically different in patients with
      any abnormal features of plain radiography as well as histology grade.
      CONCLUSION: No radiographic findings and histological grade of GCT can predict
      tumor recurrence after curettage procedure. Compared with wide excision, risk of
      local recurrence in patients that received treatment with curettage was
      significantly higher. However the choice of treatment should be balanced between
      preserving maximal joint function and risks of tumor recurrence.

PMID- 22145510
TI  - Utility of 8F-FDG PET/CT in well differentiated thyroid carcinoma with high serum
      antithyroglobulin antibody.
AB  - OBJECTIVE: Evaluate the utility of 18F-FDG PET/CT in the follow-up of
      differentiated thyroid cancer (DTC) patients with high serum antithyroglobulin
      antibody (TgAb) but negative serum thyroglobulin (Tg) measurements and negative
      131I whole-body scans (WBS). MATERIAL AND METHOD: The present study included 22
      consecutive patients with high serum TgAb levels. They had negative serum Tg
      measurements and negative 131I WBS. PET/CT was performed 60 min after intravenous
      injection of 227.55-455.47 MBq (6.15-12.31 mCi) of 18F-FDG using a combined
      PET/CT scanner. Co-registered CT images were used to differentiate physiologic
      from pathologic tracer uptake. Findings on 18F-FDG PET/CT were correlated with
      tissue pathology follow-up imaging or clinical follow-up served as a reference.
      RESULTS: Twenty-two well differentiated thyroid cancerpatients participated.
      Twelve had positive findings on 18F-FDG PET/CT six were true positives and six
      were false-positives. 18F-FDG PET/CT results were true negative in 10 patients
      and the authors found no false-negative patients in the present study. The
      overall sensitivity, specificity and accuracy of 18F-FDG PET/CT were 100%, 62.5%
      and 72.7%, respectively. TgAb levels, which are appropriated for sending DTC
      patient who are 131I WBS negative but have elevated serum TgAb levels to undergo
      18F-FDG PET/CT scan, should be more than or equal to 414.6 IU/ml. Results should
      be highly consider positive if max SUV value is equal or greater than 4.5.
      CONCLUSION: 18F-FDG PET/CT is a useful tool for localizing recurrent or
      metastatic DTC patients, who have negative 131I WBS but elevated serum TgAb
      levels. The authors recommend its use in clinical management of selected cases
      regardless of the TgAb level being more than or equal to 415 IU/ml.

PMID- 22145511
TI  - Change in quality of life of disabled patients after intensive inpatient
      rehabilitation at Siriraj Hospital.
AB  - OBJECTIVE: To compare the quality of life (QOL) before and after intensive
      rehabilitation of disabled patients and to examine the factors associated with
      the change in QOL. MATERIAL AND METHOD: A retrospective chart review of 200
      disabled patients who were admitted for intensive rehabilitation between 2006 and
      2009. The Thai abbreviated version of World Health Organization quality of life
      (WHOQOL-BREF-THAI) was used to assess QOL. Demographic data, physical and
      psychosocial status, Modified Barthel ADL Index (BAI) were collected and analyzed
      for the association with WHOQOL-BREF-THAI score changes. RESULTS: One hundred
      seventeen (58.5%) males and 83 (41.5%) females with mean age 55.6 (SD 17.9) years
      old participated in this study. Various principal diagnoses were included; 112
      (56%) stroke, 54 (27%) spinal cord injury and 34 (17%) other diagnoses. After the
      intensive rehabilitation, quality of life perception was improved in 164 (82%)
      disabled patients. There was significant difference in mean WHOQOL-BREF-THAI
      scores on admission and at discharge which were 81.3 (SD 11.2) and 85.5 (SD 11.0)
      respectively with the p-value < 0.001. The mean changed score was 4.2 (SD 8.0).
      However, four domains of QOL were improved except the social domain. The factors
      associated with the disabled patients who were non-improved in WHOQOL-BREF-THAI
      score after rehabilitation were having non-familial caregiver (OR 5.8, 95% CI 2.1
      to 16.0) and joint stiffness (OR 4.1, 95% CI 1.7 to 9.9). CONCLUSION: Intensive
      inpatient rehabilitation can significantly improve quality of life in the
      disabled patients with various primary diagnoses. Having joint stiffness prior to
      rehabilitation and non-availability of familial members for taking care are the
      factors associated with the poor outcome in QOL perception.

PMID- 22145512
TI  - Quality of life among the traumatic spinal cord injured patients.
AB  - OBJECTIVES: To study the quality of life among the traumatic spinal cord injured
      patients and to identify the factors related with the quality of life in the good
      level of such patients. MATERIAL AND METHOD: The traumatic SCI patients who had
      been treated in the Department of Rehabilitation Medicine, Siriraj Hospital,
      Bangkok, Thailand from January 2003 until August 2009 were interviewed for the
      demographic data. The injury related data were obtained from the medical records.
      The WHOQOL-BREF-Thai was used to acquire the QOL score, which would be
      interpreted as poor fair, and good QOL level according to the questionnaire. The
      Center for Epidemiologic Studies Depression scale and the modified Barthel Index
      (BI) were used to assess depression, and functional disability respectively. The
      median split method was used to divide the participants into two groups as good
      and poor QOL groups. The Chi-square and Independent Sample t-test were performed
      to determine the difference between these two groups and multivariate logistic
      regression was used to analyze the factors associated with the good QOL. P-value
      < 0.05 was accepted as statistical significance. RESULTS: Sixty-seven patients
      (49 males and 18 females) with a mean age 36.54 +/- 11.46 years old participated
      the present study. They suffered from traffic accident 67.2%, gunshot 16.4%, fall
      from a height 11.9%, and others 4.5%. The injury levels were cervical 31.3%,
      thoracic 50.7%, and lumbosacral 18%. Most of them (60.6%) had incomplete lesion.
      Eighteen patients (26.1%) reported depression. The mean BI score was 69.71 +/-
      29.42. Three (4.5%), forty-nine (73.1%), and fifteen (22.4%) participants
      reported their QOL score in the range of poor, fair and good levels respectively.
      Using the median split method, participants with a score over 82 were classified
      as having good QOL groups and the rest were classified as having poor QOL group.
      When considering the score in each domain of the WHOQOL questionnaire, the
      differences between the good and poor QOL groups had statistical significance.
      The sufficient income (OR 13.67, 95% CI: 3.1-60.22, p = 0.001), having no
      depression (OR 7.6, 95% CI: 1.17-49.22, p = 0.033), and being employed (OR 6.88,
      95% CI: 1.44-32.94, p = 0.016) were significantly related with the good QOL.
      CONCLUSION: Most of the SCI patients determined their QOL as fair level.
      Sufficient income, having no depression, and being employed were associated with
      the good QOL.

PMID- 22145513
TI  - Bioequivalence study of 10 mg ramipril tablets in healthy Thai volunteers.
AB  - OBJECTIVE: To determine the bioequivalence of 10 mg dose of ramipril tablets
      between the test product (Ramtace 10 mg, Unison Laboratories, Thailand) and the
      reference product (Tritace 10 mg, Aventis Pharma SPA, Italy). MATERIAL AND
      METHOD: The present study was carried out with a single dose, 2-treatment, 2
      period, 2-sequence randomized crossover design under fasting condition with a
      minimum of 14 days washout period in 24 healthy Thai male and female volunteers.
      Plasma samples for determination of ramipril and ramiprilat were obtained pre
      dose and at frequent intervals for up to 72 h post dose. Ramipril and ramiprilat
      plasma concentrations were quantified by a validated method employing high
      performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). All
      ofthe pharmacokinetic parameters were investigated using non-compartmental
      analysis. RESULTS: The result demonstrated the 90% confidence interval (90%CI) of
      the geometric mean ratio (test/reference) of C max, AUC(0-72) and AUC(0-infinity)
      of ramipril were 97.26% (84.50%-111.93%), 100.70% (89.47%-113.34%) and 100.29%
      (88.90% 113.15%), respectively. For ramiprilat, the 90% CI for C max, AUC(0-72),
      and AUC(0-infinity) were 108.87% (103.00%-115.07%), 104.93% (100.50%-109.55%) and
      103.30% (98.03%-108.85%), respectively. CONCLUSION: the 90% confidence intervals
      for log-transformed geometric mean test/reference formulation ratios of primary
      parameters were entirely within 80.00%-125.00%. Thus, it can be concluded that
      the test formulation was bioequivalent to the reference formulation.

PMID- 22145514
TI  - Fetal pleural effusions with spontaneous resolution: a case report.
AB  - A 42-year-old pregnant woman was referred with massive fetal bilateral pleural
      effusions. Observation with serial ultrasound was made. The documented
      spontaneous resolution of fetal pleural effusion was recorded. Neonatal
      examination revealed a completely healthy infant with normal respiration. Fetal
      pleural effusion can cause fetal lung compression, abnormal neonatal respiration
      and finally, neonatal mortality. Regular ultrasounds are one of the supportive
      options due to spontaneous resolution that can occur in 9 to 22% of the cases.

PMID- 22145515
TI  - Cauda equina involvement in acute myeloid leukemia relapse.
AB  - Although central nervous system (CNS) involvement in acute myeloid leukemia has
      been described in about 2 to 4%, it still represents a major therapeutic problem,
      particularly cauda eqina involvement that is clinically significant and unusual.
      Here, a 22-year-old man, with underlying AML (M2-Subtype, FAB classification) and
      cytogenetic analysis resulted in 45, x, -y, t(8;21) (q22;q22)[15] whose
      presenting symptoms of low back pain and incontinence, 10 months after first
      remission, was reported. This was followed by peripheral and bone marrow relapse.
      The magnetic resonance image (MRI) findings revealed leukemic infiltration at S1
      S5 of the spinal cord canal with associated soft tissue component at presacral
      area encasing bilateral S1-S5 exiting root with heterogeneous enhancement in bone
      marrow of S2-S4. The therapeutic and prognosis implications of spinal cord
      involvement by leukemia were discussed. Because of severe morbidity, the patient
      developed bone marrow failure and died from sepsis.

PMID- 22145516
TI  - Long-term outcome of living donor liver transplantation in a Thai boy with
      hereditary tyrosinemia type I: a case report.
AB  - Hereditary tyrosinemia type I (HT-I) is an autosomal recessive inborn error of
      tyrosine metabolism, caused by mutation(s) in the gene encoding for
      fumarylacetoacetate hydrolase (FAH) enzyme. The authors report a Thai boy who
      presented at two months of age with liver failure. HT-I was diagnosed based on
      the presence of succinylacetone in urine and homozygous R237X mutations of FAH
      gene. He was started on tyrosine and phenylalanine restricted diet immediately.
      Due to a limitation of 2-(2-nitro-4-trifluoromethyl benzoyl)-1,3-cyclohexanedione
      (NTBC) therapy in Thailand, it was commenced at eight months old and used as a
      bridging therapy before liver transplantation. He had a good response to NTBC
      therapy with an improvement in liver chemistries and synthetic functions.
      Subsequently, living donor liver transplantation (LDLT) was performed at 15
      months old Long-term follow-up for 6.3 years following LDLT revealed normal
      growth, good school performance, normal liver, renal tubular, and glomerular
      functions, and without urinary excretion of succinylacetone. CONCLUSION: Liver
      transplantation is a promising treatment for patients with HT-1 when NTBC is
      unavailable, resulting in a good long-term outcome.

PMID- 22145517
TI  - Isolated orbital neurofibroma in NF-1 negative patients.
AB  - Isolated orbital neurofibroma unassociated with systemic neurofibromatosis is
      relatively rare and may be difficult to clinically differentiate from other
      orbital tumors. The authors report a case of isolated orbital neurofibroma
      without neurofibromatosis type 1.

PMID- 22145518
TI  - Whither peer review? Has the time come to go back to the drawing board?

PMID- 22145519
TI  - Taking the measure of measurement. Do you make any of these common errors?

PMID- 22145520
TI  - SOS: Summer of surveys tests NC hospital. Leadership buy-in keys to success.

PMID- 22145521
TI  - A public health perspective on health care reform.

PMID- 22145522
TI  - The constitutionality of current legal barriers to telemedicine in the United
      States: analysis and future directions of its relationship to national and
      international health care reform.
AB  - The current health care crisis in the United States compels a consideration of
      the crucial role that telemedicine could play towards deploying a pragmatic
      solution. The nation faces rising costs and difficulties in access to and quality
      of medical services. Telemedicine can potentially help to overcome these
      challenges, as it can provide new cost-effective and efficient methods of
      delivering health care across geographic distances. The full benefits and future
      potential of telemedicine, however, are constrained by overlapping, inconsistent,
      and inadequate legal and regulatory frameworks, as well as the repertoire of
      standards imposed by state governments and professional organizations. Proponents
      of these barriers claim that they are necessary to protect public health and
      safety, and that the U.S. Constitution gives states exclusive authority over
      health and safety concerns. This Article argues that such barriers not only fail
      to advance these public policy goals, but are unconstitutional when they restrict
      the practice of telemedicine across state and national borders. Furthermore, the
      interstate and international nature of telemedicine calls for increasing the
      centralized authority of the federal government; this position is consistent with
      the U.S. Constitution and other governing principles. Finally, this Article
      observes that the U.S. experience bears some similarities to that of other
      nations, and represents a microcosm of the international community's need and
      struggle to develop a uniform telemedicine regime. Just as with state governments
      in the U.S., nations are no longer able to view health care as a traditional
      domestic concern and must consider nontraditional options to resolve the dilemmas
      of rising costs and discontent in the delivery of health care to their people.

PMID- 22145523
TI  - Medical liability and health care reform.
AB  - We examine the impact of the Affordable Care Act (ACA) on medical liability and
      the controversy over whether federal medical reform including a damages cap could
      make a useful contribution to health care reform. By providing guaranteed access
      to health care insurance at community rates, the ACA could reduce the problem of
      under-compensation resulting from damages caps. However, it may also exacerbate
      the problem of under-claiming in the malpractice system, thereby reducing
      incentives to invest in loss prevention activities. Shifting losses from
      liability insurers to health insurers could further undermine the already weak
      deterrent effect of the medical liability system. Republicans in Congress and
      physician groups both pushed for the adoption of a federal damages cap as part of
      health care reform. Physician support for damages caps could be explained by
      concerns about the insurance cycle and the consequent instability of the market.
      Our own study presented here suggests that there is greater insurance market
      stability in states with caps on non-economic damages. Republicans in Congress
      argued that the enactment of damages caps would reduce aggregate health care
      costs. The Congressional Budget Office included savings from reduced health care
      utilization in its estimates of cost savings that would result from the enactment
      of a federal damages cap. But notwithstanding recent opinions offered by the CBO,
      it is not clear that caps will significantly reduce health care costs or that any
      savings will be passed on to consumers. The ACA included funding for state level
      demonstration projects for promising reforms such as offer and disclosure and
      health courts, but at this time the benefits of these reforms are also uncertain.
      There is a need for further studies on these issues.

PMID- 22145524
TI  - Federal Trade Commission's authority to regulate marketing to children: deceptive
      vs. unfair rulemaking.
AB  - Food and beverage marketing directed at children is of increasing concern to the
      public health and legal communities. The new administration at the Federal Trade
      Commission and abundant science on the topic make it a particularly opportune
      time for the government to reconsider regulating marketing directed at youth.
      This Article analyzes the Commission's authority to regulate food and beverage
      marketing directed at children under its jurisdiction over unfair and deceptive
      acts and practices to determine which avenue is most viable. The author finds
      that the Federal Trade Commission has the authority to regulate deceptive
      marketing practices directed at vulnerable populations. Although the Commission
      can issue individual orders, its remedial power to initiate rules would better
      address the pervasiveness of modern marketing practices. The Commission does not
      currently have the power to regulate unfair marketing to children; however, even
      if Congress reinstated this authority, the Commission's authority over deceptive
      marketing may be preferable to regulate these practices. Deceptive communications
      are not protected by the First Amendment and the deceptive standard matches the
      science associated with marketing to children. The Federal Trade Commission has
      the authority to initiate rulemaking in the realm of food and beverage marketing
      to children as deceptive communications in interstate commerce, in violation of
      the Federal Trade Commission Act. However, to effectuate this process, Congress
      would need to grant the Commission the authority to do so under the
      Administrative Procedures Act.

PMID- 22145525
TI  - FDA preemption of drug and device labeling: who should decide what goes on a drug
      label?
AB  - The Supreme Court decided an issue that is critical to consumer health and safety
      last year. In April 2009, the Supreme Court held that extensive FDA regulation of
      drugs did not preempt a state law claim that an additional warning on the label
      was necessary to make the drug reasonably safe for use. Thus, states--and even
      courts and juries--are now free to cast their vote on what a drug label should
      say. This is in direct contrast to medical devices, where the federal statute
      regulating medical devices expressly provides that state regulations are
      preempted. This Article discusses basic preemption principles and drugs, and
      explores the policy ramifications of pro- and anti-preemption policy in the
      healthcare industry.

PMID- 22145526
TI  - Increasing consent for organ donation: mandated choice, individual autonomy, and
      informed consent.

PMID- 22145527
TI  - DNA to play: Major League Baseball's use of DNA testing on Central and South
      American prospects in the age of the Genetic Information Nondiscrimination Act of
      2008.

PMID- 22145528
TI  - Where are all the citizen suits?: the failure of safe drinking water enforcement
      in the United States.

PMID- 22145529
TI  - Identification of true EST alignments for recognising transcribed regions.
AB  - Transcribed regions can be determined by aligning Expressed Sequence Tags (ESTs)
      with genome sequences. The kernel of this strategy is to effectively distinguish
      true EST alignments from spurious ones. In this study, three measures including
      Direction Check, Identity Check and Terminal Check were introduced to more
      effectively eliminate spurious EST alignments. On the basis of these introduced
      measures and other widely used measures, a computational tool, named ESTCleanser,
      has been developed to identify true EST alignments for obtaining reliable
      transcribed regions. The performance of ESTCleanser has been evaluated on the
      well-annotated human ENCyclopedia of DNA Elements (ENCODE) regions using human
      ESTs in the dbEST database. The evaluation results show that the accuracy of
      ESTCleanser at exon and intron levels is more remarkably enhanced than that of
      UCSC-spliced EST alignments. This work would be helpful to EST-based researches
      on finding new genes, complementing genome annotation, recognising alternative
      splicing events and Single Nucleotide Polymorphisms (SNPs), etc.

PMID- 22145530
TI  - Multi-platform gene-expression mining and marker gene analysis.
AB  - Gene-expression data are now widely available and used for a wide range of
      clinical and diagnostic purposes. A key challenge is to select a few significant
      marker genes for biological studies. While it is feasible to find important genes
      from a single gene-expression data set, it is often more meaningful to compare
      the results from different but related data sets together, especially for
      multiple gene-expression data sets arising from different studies of a common
      organism or phenotype. In this paper, we present a novel framework to exploit the
      commonalities across different data sets by jointly learning from different data
      sets simultaneously through multi-task feature learning. By identifying a common
      subspace of genes, we can help biologists find important marker genes that span
      different evolutionary periods in the life cycle of cancer development. The genes
      thus found are more stable and more significant. Our experimental results
      demonstrate that more accurate models can be built using multiple data sets based
      on fewer labelled examples. To the best of our knowledge, we are among the first
      to introduce multi-task learning in the bioinformatics community to solve the
      lack of data problem.

PMID- 22145531
TI  - Robust classification ensemble method for microarray data.
AB  - The objective of this study is to develop an accurate and robust classification
      ensemble method suitable for microarray data with noises. We proposed an
      algorithm, pattern match (PM)-bagging, which performs well in accuracy and is
      robust to noise variables and noise observations. From the experiments with real
      data set, the performance of the proposed method is found quite comparable and
      not much degraded even when the data set has noise variables or noise
      observations, while some other ensemble methods showed degradations of
      performance. A bias and variance decomposition showed that the success of the
      proposed method is due to an effective reduction of both bias and variance.

PMID- 22145532
TI  - Computational identification of potential microRNA network biomarkers for the
      progression stages of gastric cancer.
AB  - MicroRNAs (miRNAs) are potential biomarkers in the diagnosis of human disease. In
      this study, a novel concept, the miRNA network biomarker, was proposed for the
      selection of biomarkers. Each miRNA network biomarker contains miRNA targets, as
      well as Transcription Factors (TFs), that affect the miRNA expression. The
      obtained biomarkers were applied to classifying expression data sets in different
      progression stages from chronic gastritis to gastric cancer. Furthermore, these
      biomarkers could accurately (94%) discriminate gastric cancer samples from normal
      samples in another data set. Angiogenesis-related pathways and genes were found
      to be enriched in these network biomarkers.

PMID- 22145533
TI  - MentalSquares: a generic bipolar Support Vector Machine for psychiatric disorder
      classification, diagnostic analysis and neurobiological data mining.
AB  - MentalSquares (MSQs)--an equilibrium-based dimensional approach is presented for
      the classification and diagnostic analysis of psychological conditions with
      Bipolar Disorders (BPDs) as an example. While a Support Vector Machine (SVM) is
      defined in Hilbert space. A MSQ can be considered as a generic SVM for improved
      classification. Different from the traditional categorical model of BPDs, the
      generic approach focuses on the balance of two poles of mental equilibrium.
      Preliminary results show that this new approach has a number of advantages over
      existing models. The generic model is analytically illustrated with public domain
      clinical examples and well-known empirical clinical knowledge. Its clinical and
      computerised operability is illustrated. Its potential of being a practical
      method for the classification and analysis of neurobiological patterns and drug
      effects is discussed.

PMID- 22145534
TI  - CarGene: characterisation of sets of genes based on metabolic pathways analysis.
AB  - The great amount of biological information provides scientists with an
      incomparable framework for testing the results of new algorithms. Several tools
      have been developed for analysing gene-enrichment and most of them are Gene
      Ontology-based tools. We developed a Kyoto Encyclopedia of Genes and Genomes
      (Kegg)-based tool that provides a friendly graphical environment for analysing
      gene-enrichment. The tool integrates two statistical corrections and
      simultaneously analysing the information about many groups of genes in both
      visual and textual manner. We tested the usefulness of our approach on a previous
      analysis (Huttenshower et al.). Furthermore, our tool is freely available
      (http://www.upo.es/eps/bigs/cargene.html).

PMID- 22145535
TI  - Complete coding sequence, sequence analysis and transmembrane topology modelling
      of Trypanosoma brucei rhodesiense putative oligosaccharyl transferase (TbOST II).
AB  - The partial nucleotide sequence of putative Trypanosoma brucei rhodesiense
      oligosaccharyl transferase gene was previously reported. Here, we describe the
      determination of its full-length nucleotide sequence by Inverse PCR (IPCR),
      subsequent biological sequence analysis and transmembrane topology modelling. The
      full-length DNA sequence has an Open Reading Frame (ORF) of 2406 bp and encodes a
      polypeptide of 801 amino acid residues. Protein and DNA sequence analyses
      revealed that homologues within the genome of other kinetoplastid and various
      origins exist. Protein topology analysis predicted that Trypanosoma brucei
      rhodesiense putative oligosaccharyl transferase clone II (TbOST II) is a
      transmembrane protein with transmembrane helices in probably an N(cytosol)
      C(cytosol) orientation. Data from the GenBank database assembly and sequence
      analyses in general clearly state that TbOST II is the STT3 subunit of OST in
      T.b. rhodesiense that necessitates further characterisation and functional
      studies with RNAi. TbOST II sequence had been deposited in the GenBank (accession
      number GU245937).

PMID- 22145536
TI  - Student pursuers: an investigation of pursuit and stalking in the student-faculty
      relationship.
AB  - Data from faculty and students provide information on the prevalence of unwanted
      pursuit and stalking in the student-faculty relationship. Among faculty, 67.8%
      reported unwanted pursuit. For the most serious case, 6%-11% met criteria for
      stalking. Among students, 4.1% reported engaging in unwanted pursuit of faculty.
      Both faculty and students perceived anger (especially for male students) to be
      the motive for student unwanted pursuit/stalking, with some endorsement of
      romantic interest and concern about the role of mental illness. Sex differences
      suggest female faculty members are more often a target of unwanted pursuit or
      stalking and more likely to experience fear.

PMID- 22145537
TI  - Gender differences in acknowledgment of stalking victimization: results from the
      NCVS stalking supplement.
AB  - Research suggests that a significant portion of victims of interpersonal violence
      do not acknowledge or label their experience as a criminal victimization. Studies
      exploring unacknowledged victimizations have found that individuals are more
      likely to acknowledge victimization when the experience meets certain, often
      stereotypical criteria. This study addressed this issue by integrating literature
      on victim acknowledgment and stalking victimization to identify correlates of
      victimization acknowledgment among stalking victims. Data were drawn from the
      2006 stalking supplement to the National Crime Victimization Survey (NCVS), and
      the sample included both female and male victims of stalking. Findings revealed
      support for a "classic stalking script," which included a reliance on
      stereotypical types of stalking behavior (i.e., being spied on) that were shown
      to increase acknowledgment for victims of stalking. Results also described gender
      based correlates of victimization acknowledgment.

PMID- 22145538
TI  - Examining verbal and physical retaliation against kinship insults.
AB  - This study examined how different types of insults-social status insults and
      reproductive status insults--toward one's family and friends influenced the
      likelihood of verbal and physical retaliation. Participants were given a
      questionnaire containing scenarios in which a hypothetical person insulted each
      participant's sibling, cousin, or friend. Participants indicated they were
      significantly less likely to verbally retaliate when a cousin was insulted than
      when a sibling or friend was insulted. Men were more likely to physically
      retaliate toward male insulters. Women were more likely to physically retaliate
      toward female insulters. Women were more likely to verbally retaliate than men,
      but only when the insulter was female. Both men and women were more likely to
      retaliate when a woman was insulted.

PMID- 22145539
TI  - Childhood and adolescent violent victimization and the risk of young adult
      intimate partner violence victimization.
AB  - Using a nationally representative sample of participants, this study investigates
      childhood victimization in the home and adolescent violent victimization in the
      community on the risk of being a victim of intimate partner violence (IPV),
      general violence, or both during early adulthood. The study findings indicate
      being left home alone and being physically abused during childhood, and
      adolescent violent victimization in the community had strong independent effects
      on an individual's likelihood of becoming a victim of IPV, general violence, or
      both in early adulthood. The study findings suggest a consistent pattern of
      victimization across the life course, and intervention programs need to be
      developed that address the specific needs of children and adolescents at high
      risk for home and community violent victimization.

PMID- 22145540
TI  - Sexual violence victimization among female secondary school students in eastern
      Ethiopia.
AB  - Behavioral, lifestyle, and relationship factors have all been identified as risk
      factors that increase a woman's vulnerability to sexual violence victimization.
      However, it remains unclear which risk factors most strongly increase young
      women's vulnerability to sexual violence victimization because most studies only
      examine a few factors simultaneously. Using a cross-sectional sample of 764
      female secondary school students from eastern Ethiopia, multivariate analyses
      revealed that high-rejection sensitivity, having multiple sexual partners, the
      frequent watching of pornography, and use of alcohol or other soft drugs (Khat or
      shisha) are factors associated with higher levels of sexual violence
      victimization. The overall rates of victimization is high in this group, with 68%
      of the young women studied having experienced at least one instance of sexual
      violence victimization. Based on type of sexual perpetration, 52% of the young
      women were victimized by at least one instance of sexual offence, 56% by sexual
      assault, 25% by sexual coercion, and 15% by sexual aggression. Qualitative data
      gathered from interviews of extracurricular club members and school officials and
      focus group discussion with students were used to further augment and illustrate
      results from the quantitative data. Several suggestions for intervention are
      presented in light of these results.

PMID- 22145541
TI  - Attitudes toward dating violence among college students in mainland China: an
      exploratory study.
AB  - This study investigates attitudes toward psychological and physical dating
      violence among college students in mainland China (n = 245). The results of this
      study indicate that among our sample of college students in mainland China, men
      and women were relatively similar in their attitudes toward male perpetrated and
      female perpetrated physical dating violence and female perpetrated psychological
      dating violence. As has been found in previous research, men and women in our
      sample were more accepting of female perpetrated physical and psychological
      dating violence than male perpetrated physical and psychological dating violence.
      Finally, among several variables that predicted dating violence attitudes, shame
      emerged as a potentially important variable to include in future studies on
      dating violence in Chinese populations.

PMID- 22145542
TI  - Social control correlates of arrest behavior among homeless youth in five U.S.
      cities.
AB  - This study identified homelessness, substance use, employment, and mental health
      correlates of homeless youths' arrest activity in 5 cities. Two hundred thirty
      eight street youth from Los Angeles, Austin, Denver, New Orleans, and St. Louis
      were recruited using comparable sampling strategies. Ordinary least squares (OLS)
      regression results reveal that being arrested for criminal activity is associated
      with length of homelessness, history of juvenile detention and incarceration,
      receiving income from theft, substance abuse, and mental illness. Arrests are
      also associated with interactions between lack of formal employment income and
      receiving income from theft and between drug and alcohol abuse/ dependency.
      Understanding the health and situational factors associated with homeless youths'
      delinquent activity has implications for providing more comprehensive health,
      mental health, and substance abuse services.

PMID- 22145543
TI  - Attitudes affecting physical dating violence perpetration and victimization:
      findings from adolescents in a high-risk urban community.
AB  - This study examines the associations between attitudes supporting physical dating
      violence against boys hitting girls and girls hitting boys and experiences with
      physical dating violence perpetration and victimization among youth in a high
      risk community. Cross-sectional logistic regression analyses are based on data
      from the Youth Violence Survey, conducted in 2004, and administered to more than
      80% of public school students in grades 7, 9, 11, and 12 (N = 4,131) in an urban
      school district. Findings show that attitudes supporting physical dating violence
      against boys and girls are significantly associated with physical dating violence
      perpetration and victimization. Prevention programs that seek to reduce physical
      dating violence among adolescents may benefit from including sex-specific
      attitude modification as part of a comprehensive violence prevention approach.

PMID- 22145544
TI  - Fear of property crime: examining the effects of victimization, vicarious
      victimization, and perceived risk.
AB  - Fear of crime research has primarily focused on fear of crime in general or on
      fear of specific types of violent crimes. This study builds from this line of
      research by focusing exclusively on the night fear of six types of property
      crimes, including fear of burglary while away from home, vehicle theft, bicycle
      theft, property theft, vandalism, and vehicle burglary. This study examines the
      effects of victimization, vicarious victimization, and perceived risk on fear of
      property crime. Survey data from college students reveal that victimization and
      vicarious victimization were not significant predictors of fear of property
      crime, whereas perceived risk was a consistent and significant predictor of fear
      of all property crimes.

PMID- 22145545
TI  - The traceability of carcinogenic occupational risks: state of progress in France
      compared with other European countries.
AB  - Occupational risks are constantly evolving. The complexification of these
      occupational risks, the context of the flexibility with the new forms of
      organization, the new conditions of use and the increase in occupational mobility
      are accentuating the difficulties of assessment of the deferred risks for the
      health of employees. In point of fact, if on the one hand the immediate risk
      (accidental, corrosive, caustic, explosive...) is properly taken into account, on
      the other hand this is far from the case for the deferred risk, in particular the
      carcinogenic risk. Now, the liability of employers (especially with regard to
      cancers due to asbestos) is incurred more and more often. It is they in fact who
      bear the brunt of the prevention of occupational risks in France. Since 2002, the
      French employer has thus a veritable safety performance obligation in terms of
      preserving the health of the employees. Now, one of the vital keys to the
      prevention of deferred occupational risks resides in the traceability of the
      exposures that the employees have undergone throughout their working lives, in
      particular carcinogenic. In this context, the follow-up of the exposure of the
      employees to carcinogenic risks then becomes a necessity. The awareness of the
      necessity of setting in place an occupational exposure follow-up tool is not
      recent. Traceability procedures exist moreover in a certain number of countries,
      but so far in France we have only seen ad hoc experiments of a very limited
      nature for the identification and storage of occupational exposure. These are not
      of an exhaustive nature or only relate to mainly medical data. There is no
      systematic tool for the follow-up of carcinogenic exposure. This is due, on the
      one hand to the technical difficulties of setting in place standardized tools for
      exposure data collation, and on the other hand to the fact that the traceability
      of the personal information collated may raise ethical issues of reconciling the
      right to health of the employees with their right to work and the observing of
      their individual liberties; lastly, because the amassing of such information may
      raise issues of liability, in particular for the employer exposing its employees
      to carcinogens. Such issues transcend frontiers and have to be taken into
      consideration in order for progress to be made in the area of traceability of
      occupational exposure. Very few studies have been devoted to this subject so
      crucial to the prevention of occupational diseases. We propose, initially, to
      define traceability and the issues involved. Next, we will consider the current
      regulatory obligations on employers in France that may contribute to the
      traceability of occupational exposure and their limits. Then we will examine the
      brakes--the legal, ethical and technical difficulties that explain why France is
      lagging behind in this field. Finally, we will study the French perspectives with
      regard to the European advances in the traceability area.

PMID- 22145546
TI  - Access to healthcare services as a human right.
AB  - The existence of a right to healthcare or, at least, access to healthcare
      services, is a right that exists in terms of the Bill of Rights in the
      Constitution of the Republic of South Africa, 1996. This article explores the
      scope and ambit of the right and its meaning within the context of both of
      constitutional directives, the duties imposed upon the State to progressively
      realise the right for its citizens and the practical implications of the right
      with reference to existing healthcare infrastructure in the Republic of South
      Africa.

PMID- 22145547
TI  - Inadequate treatment of pain: time for the South African courts to redress this
      human rights violation?
AB  - In the case of 90 per cent of patients, pain can be relieved adequately, but in
      80 per cent of these cases this is not done, despite the fact that effective pain
      medication is available. More than three decades ago, the under-treatment of pain
      had already been identified as a major global problem. Human dignity requires
      that treatable pain be relieved. Although attempts have been made to address this
      unnecessary human suffering, there are a number of reasons why little progress
      has been made. Fear of the regulatory authority has been mentioned, but in South
      Africa this is not the case. A lack of knowledge and archaic views have resulted
      in the standard practice of mismanaging pain. Diverging views on whether the
      health care system's failure to treat patient pain adequately needs corrective
      action by the judiciary will be discussed. An argument will be made out that the
      courts should reconsider the standard practice and the question of what is
      reasonable in regard to pain treatment. The "failure to treat pain adequately"
      should be recognised as a separate and independent form of medical negligence.
      Other possible causes of action will also be discussed. Improvements in pain
      management require simultaneous initiatives in medicine, law and ethics.

PMID- 22145548
TI  - Female genital mutilation: medico-legal issues.
AB  - The rising prevalence and severe impact of HIV/AIDS in relation to women still
      persists in South Africa. Both economically and socially the HIV/AIDS pandemic
      strikes women the hardest, with disadvantaged black women mainly at risk of
      higher infection. The theoretical framework of this paper focuses on the
      connection between HIV/AIDS, sexual inequalities and sexual violence, and more
      precisely, female genital mutilation, a cultural practice and custom which
      amplifies women's exposure to HIV. Pertinent to this focus is inescapably an
      analysis of apparent threats to precise essential human rights as a result of the
      continued use of the practice of female genital mutilation in South Africa.

PMID- 22145549
TI  - The place for emotions in professional carers' thinking: reflections on two
      cases.
AB  - How do carers know what is right for their patient? What can they do further to
      relying on the two pillars of knowledge and ethics? Knowledge foregrounds
      rational decision-making based on scientific evidence. It allows cost-benefit
      rationalization and the choice of the best feasible objective. The steady advance
      of medical science drives responsible carers to keep their knowledge and skills
      up-to-date. Bioethics grants primary attention to the prevention of causing harm
      in general, to pursuant of patients' subjective wellbeing and to allow the latter
      enjoy their autonomy and to guarantee them the sense of justice. There are,
      however, cases where these values collide and any care decision violates one
      principle or another. How are carers expected to act then? This article concerns
      the choices made by carers, as presented and discussed in two cases. These cases
      deal with a clash between two principles: parenthood vs. fertility, religious
      rite vs. social affiliation. This class has generated an ethical dilemma. In each
      case carers try to justify their choices by expert knowledge and other ethical
      values, but later reflection reveals that the predominant element in 'solving'
      these dilemmas was "emotions." Professional training submits that: 'Set aside
      feelings in order to keep your thinking 'straight.' However, reality proves this
      simply infeasible. The more complex the medical-ethical situation, it is more
      likely that "emotions" take over. We have no choice as responsible carers but to
      allow our emotions the status of a factor of influence in their own right.
      Nowadays, a basic medical training for doctors and nurses offers an integrated
      body of knowledge and therapeutic skills. In addition, trainees are introduced to
      bioethics, supposedly sufficient to guide their future steps in their chosen
      profession. But how does this training in fact shape their future ethical
      conduct, if at all? How does it affect their ability to maintain ethical
      responsibility throughout therapeutic interactions? Perhaps there are other
      factors which govern the individual's conduct and his/her ethical responsibility?
      Simulation exercises were conducted, designed to induce healthcare professionals
      to reflect on the ethics of their own decision-making. The results demonstrated
      that therapeutic skills and familiarity with bioethical principles are not the
      sole factors governing the individual's ethical conduct. It turns out that
      emotions and feelings play a key part; this at once raises the question as to
      whether a medical training for doctors and nurses, in its current format,
      concerns itself with emotions and with how emotions shape a therapeutic
      personality. If not, then our training designers have food for thought. How can
      such training make trainees more aware of the power of their emotions? And, what
      are the ramifications on daily practice concerning ethical responsibility?
      Another question concerns the possible proper methods for mastering the
      theoretical materials and the practical techniques that promote emotional self
      development?

PMID- 22145550
TI  - Attitudes towards academic cheating during nursing studies.
AB  - Nursing Student cheating is a cause for concern. Research to examine the
      attitudes of nursing students to academic cheating and what this may predict for
      their professional practice after graduation was conducted. A convenience sample
      of 228 students found a strong tendency to see academic dishonesty as normative.
      The most compelling factor in the decision to plagiarize or not is the 'survival
      instinct'. This does not necessarily mean that the student perceives copying as
      ethical. Correlations were found between personal characteristics and attitude
      towards cheating. It is recommended: (a) To raise awareness of the frequency of
      academic dishonesty and its implications for professional malpractice. (b) To
      institute a policy promoting academic integrity by ensuring all involved,
      including the students become partners in rule enforcement. (c) To establish a
      policy of penalties sufficiently strong to deter all, students and staff, from
      dishonest practices.

PMID- 22145551
TI  - Interpreting the declaration of Helsinki (2008): "must", "should" and different
      kinds of obligation.
AB  - The Declaration of Helsinki is widely regarded as the preeminent code of research
      ethics. Revised six times since 1964, the versions differ in their substantive
      requirements, and also in the way that obligations are expressed, especially
      regarding the use of the prescriptors "should" and "must". The 2000 version
      contained roughly two-thirds "should" versus one-third " must". But this ratio
      was inversed in the final 2008 version--although in its penultimate draft
      practically all occurrences of "must" had been replaced with "should". We
      consider and analyze the significance of these variations for policy and
      practice. We argue that the Declaration can plausibly be viewed as 'soft law'. In
      interpreting it in legislative and jurisdictional contexts the terms "should" and
      "must" cannot be seen as synonymous. Even if the soft-law claim is rejected, and
      the Declaration is viewed as providing ethical guidance only, the question of how
      to interpret "should" and "must" remains. We explore three possible
      interpretations: categorical versus hypothetical requirements; perfect versus
      imperfect obligations; and aspiration versus obligation. We conclude that the
      most plausible way of understanding the distinction is in relation to the
      strength of the categorical obligations which the Declaration seeks to set out.

PMID- 22145552
TI  - The Mental Health Act 2007 in England and Wales: the impact on perceived patient
      risk profiles.
AB  - The Mental Health Act 2007 in England and Wales introduces several amending
      measures to the Mental Health Act 1983, some of which re-emphasize a commitment
      to the facilitation of patients' rights. However, the dominant policy driver
      behind this reform process has been and remains risk and its management. Although
      this policy has been considerably diluted and is more subtle in form from
      Parliament's initial plans, it remains strong. This paper considers some early
      findings from an ongoing study that is concerned with evaluating how the risk
      agenda, as a policy driver, impacts upon institutions, individuals, and other key
      stakeholders involved in mental health decisions. The permeation of the risk
      agenda within the legislation could potentially bring about significant changes
      in the practice of professionals involved in decisions to compulsorily detain,
      discharge and treat individuals under the 1983 Act.

PMID- 22145553
TI  - The phenomenon of physical aggression against health service personnel: different
      perspectives.
AB  - The doctor-patient relationship has undergone important changes in recent years.
      Increasing levels of distrust on the part of patients toward professionals and
      institutions have led to an increase in the number of conflicts that end in
      violent actions against health service personnel. The aim of this study is to
      analyse this phenomenon in the public welfare services of the Region of Murcia
      (Spain), based on an analysis of accusations presented by doctors in the courts
      between 2006 and April 2008. The conclusion reached in this study can presumably
      be extrapolated to the rest of Spain. The violent reactions in question resulted
      from patients demanding drug prescriptions, the prolongation of sick leave and
      the demand for diagnostic tests. The Public Health Services provide directives
      for the anticipation of and abstention from such situations, emphasize the
      training of professionals in communication skills, the promotion of skills of
      negotiation and emotional self-control. Other measures include the installation
      of alarms, intercoms and video cameras, contracting security companies,
      collaboration with the police and posters in health facilities warning that legal
      action will be taken. Nevertheless, given the obvious inadequacy of the above
      mentioned measures Plans of Prevention have been put in place. In addition legal
      defence has been granted to all such professionals. From a judicial point of
      view, these aggressions are judged as minor crimes of injury or insult. The most
      recent view taken on such conduct is to consider it as a crime of attempt or an
      offence against the authority, which has been confirmed in law by the recent
      judgment passed down by the Spanish High Court on 4th December, 2007.

PMID- 22145554
TI  - Application and synthesis of statistical evidence in medical negligence.
AB  - Statistical evidence has direct effects on the practice of medicine and the
      standards set by the profession. In turn, this has implications in medical
      negligence, particularly with respect to the standard of care expected of health
      care providers. In this article, we investigate the role that statistical
      evidence plays in the interaction between medicine and law when appropriate
      medical care is considered. A quantitative appraisal of such evidence is
      suggested in order to maintain the high objective professional standards demanded
      by both medicine and law.

PMID- 22145555
TI  - Rethinking the meaning of being a scientist--the role of scientific integrity
      boards and some thoughts about scientific culture.
AB  - Biomedicine is a fast moving and often challenging research field. To this
      extent, it seems that preserving one's integrity is becoming more and more
      complex and occasionally stressful for individual researchers. Highly competitive
      funding and publication, the commercialization of biomedicine in general, the
      media hype about some scientific fields, the politicization of research and
      higher education, and, last but not least, the increasing specialization
      necessary to deal with increasingly sophisticated experimental systems and
      technologies are aspects of this complexity. While guidelines and overseeing
      control boards are important regulatory instruments, which also serve to enhance
      awareness of scientific integrity and to increase transparency, are not
      sufficient to maintain and further develop a positive academic climate that
      motivates the community to adhere to high and consistent professional ethics.
      Here, scientific misconduct and misbehaviour will be illustrated by referring to
      well-documented cases and to the need for improving scientific culture, which
      will be discussed in depth.

PMID- 22145556
TI  - Provision 280 of the Turkish Penal Code: infringes on physician's dignity.
AB  - Every medical interference could be interpreted as an intervention into one's
      physical integrity and physical autonomy. This fact has brought along the
      necessity of determining the responsibilities of physicians, apotheosized
      throughout history from time to time, and to define the limits of the medical
      profession. The Turkish Penal Code (TPC) is the kind of legislation that imposes
      such limits. A revised version of the TPC has been in effect since June 1st,
      2005. Ever since its enforcement, the TPC has attracted fierce criticism from
      several counts. However, Provision 280 is considered to be the most problematic
      one with regard to medical ethics. Along with several critical aspects, this
      provision stipulates almost a psychological violence for all health care
      professionals, particularly for the physicians as a matter of intervening with
      human dignity. The above-mentioned provision 280 needs to be annulled promptly in
      order to prevent physicians from remaining under psychological pressure while
      practicing their professions, as well as maintaining the moral values of the
      profession.

PMID- 22145557
TI  - Illicit drugs, testing, prevention and work in France: ethical and legal issues.
AB  - The use of illicit drugs in the workplace raises issues pertaining to prevention
      and safety and the responsibility of the various members of staff. It also brings
      into question the interface between work and private life. If employees are in
      theory responsible for their own safety and risk heavy penalties in the event of
      the consumption of illicit drugs in the workplace, such behaviour has to be
      proved. In reality, the worker can only be partially and marginally held liable,
      given the fact that the employer is prohibited from infringing on their rights
      and liberties (restrictions on the searching of their personal belongings and
      lockers as well as on the carrying out of breath testing and saliva testing under
      restrictive conditions). Employers have for their part a broader range of
      responsibilities and, above all, an absolute obligation to achieve specific goals
      in terms of health and safety resulting in the need to take action. In accordance
      with the International Labour Organization recommendations, European and national
      legislation, the employer has to implement a suitable preventive policy. However,
      where is the balance between prevention and repression? Very few studies have
      raised these issues and our aim is to precisely situate the place of drug testing
      in the employer's repressive arsenal in France and to try to answer the legal and
      ethical issues raised. Thus, for example, repression can only be acceptable when
      it deals with moderate and non-addicted users, or it could be tantamount to
      discrimination.

PMID- 22145558
TI  - Can unethically produced data be used ethically?
AB  - BACKGROUND: Breaches of medical ethics such as the failure to obtain consent and
      the failure to allow exit from an experiment, are but two violations that
      undermine scientific and medical research. This paper provides the results of a
      survey that asked medical researchers and scientists their views on the use of
      data from unethical medical experiments. METHODS: Questionnaires were sent to
      sixty-eight physicians, bioethicists, psychiatrists and scientists. Four cases of
      unethical experiments were presented and questions related to the use of the data
      from those experiments were posed to the participants. RESULTS: Responses were
      obtained from 47% (32) of those approached. CONCLUSIONS: The majority of
      respondents replied that they would use the data if it would save a life or
      improve the quality of life of an individual or members of society as a whole.

PMID- 22145559
TI  - Towards beneficence for young children in research: challenges for bioethics
      committees.
AB  - Bioethics committees are the focus of international scrutiny, particularly in
      relation to their application of the principle of beneficence, ensuring that
      risks incurred in research are outweighed by benefits to those involved directly
      and to the broader society. Beneficence, in turn, has become an international
      focus in research with young children, who hitherto had been rarely seen or heard
      in their own right in research. Twenty years ago, The United Nations Convention
      on the Rights of the Child 1989 raised global awareness of children's human
      rights to both participation and protection, and articulation of children's
      rights came to inform understandings of young children's rights in research. In
      the intervening period, countries such as Australia came to favour child
      protection and risk minimisation in research over the notion of children's bone
      fide participation in research. A key element of the protection regime was the
      theoretical understanding of young children as developmentally unable and,
      therefore, unfit to understand, consent to and fully participate as research
      participants. This understanding has been challenged in recent decades by new
      theoretical understandings of children's competence, where children can be seen
      to demonstrate competence, even at an early age, in consenting to, participating
      in and withdrawing from research. The paper draws on these understandings to
      provide insights for human research gatekeepers, such as bioethics committees, to
      deal with the challenges of research with young children and to realize the
      benefits that may accrue to children in research.

PMID- 22145560
TI  - Bioethics committees and examining consent within the patient-physician
      relationship in Turkey.
AB  - Clinical exercises include questions about a physician's behaviour, decision
      making process, values, rights and responsibilities, as much as the scientific
      technical questions concerning the disease. Some of these questions may be easily
      answered, for there are well-constructed activity options that have found
      widespread acceptance regarding what has to be done. However, it is quite
      difficult to answer the questions with problematic options, or the ones on which
      a compromised attitude is not present. Patient participation in treatment-related
      decision-making has been promoted as being ethically and clinically desirable in
      Western countries. Several studies have indicated that patient participation in
      decision-making has a positive influence on their health outcomes, thereby
      increasing patient satisfaction regarding medical care and promoting patient
      autonomy. Over the last decade, patient involvement in treatment-related decision
      making has been widely advocated in Turkey, where patient-physician encounters
      are still under the influence of the long-standing tradition of paternalism.
      Despite this profound change in clinical practice, studies investigating the
      actual preferences of Turkish people regarding involvement in treatment-related
      decision-making are limited. In Turkey, to protect the rights of patients,
      current Govermental requirements mandate that all human biomedical research and
      medical intervention be accompanied by a consent form that contains the
      information necessary for an informed decision. In addition, they require that
      the information provided to the subject or the representative shall be explained
      in appropriate language. Especially after the new regulations in the Turkish
      Penal Code, physicians and nurses have started to be more sensitive towards
      informed consent and have become more conscious about their responsibilities. It
      has started to be questioned more, and as a result, the problems experienced
      about patient consent in medical applications created new ethical dilemmas.
      Informed consent is acknowledged to be the most essential constituent of patient
      rights today. In this paper, after introducing a general overview of the
      significance and requirements of informed consent, we will consecutively discuss
      the decision making and informed consent process, legal arrangements concerning
      this issue in Turkey, the approaches of physicians and patients towards the
      topic, and regarding informed consent, we will discuss the responsibilities of
      hospital ethics committees.

PMID- 22145561
TI  - Predictive genetic tests for employment purposes: why not?
AB  - Given the uncertainty that characterizes genetic information in relation to the
      pressing ethical and deontological questions involved in their acquisition and
      subsequent use, and in the context of enormous social relevance, it is essential
      to have international legislation authorizing the use of such tests for genetic
      monitoring of employed persons compatible with the need to protect their privacy.

PMID- 22145562
TI  - Legal values as tools for promoting harmony.
AB  - The doctrine of informed consent has the effect of allowing the mentally
      competent adult patient to exercise individual choice in any proposed medical
      treatment. The ethical principles primarily inherent in this doctrine would be
      the principles of autonomy and beneficence. However, it is argued in this essay
      that the concept and meaning of autonomy might be vastly different between
      western and eastern communities. Consequently the doctrine of informed consent
      will lead to a different meaning in these different societies. The essay also
      raises the implication of transplanting legal doctrines into societies which
      might not be fully prepared to implement the ideal contained in the doctrine of
      informed consent.

PMID- 22145563
TI  - Withdrawing and withholding medical treatment: a comparative study between the
      Malaysian, English and Islamic law.
AB  - The permissibility and lawfulness of withdrawing and withholding medical
      treatment has attracted considerable debates and criticisms, as the legal issues
      are drawn into entering the slippery slope of euthanasia. Proponents of "sanctity
      of life" views that withdrawing and withholding medical treatment with knowledge
      that death would result is still within the sphere of euthanasia, whereas
      proponents of "quality of life" argue that it is not, as death is not intended.
      Their arguments maintain that for patients who are totally dependant on machines
      to ensure the work of some bodily functions, living may amount to little more
      than survival as dying is prolonged. Furthermore, the prolonging of life of the
      dying patient has profound implications on patients themselves, their relatives,
      dependants and medical providers. Thus, withdrawing and withholding medical
      treatment would not only respect a patient's right to self-determination, by
      allowing them to die in their underlying condition, but will ensure that medical
      providers are able to concentrate on more worthwhile treatments. This paper
      discusses the intractable difficulties with the moral distinction between
      withholding and withdrawing treatment and euthanasia, as well as makes a
      comparative study between the present state of law in Malaysia and England on
      this issue. The paper further highlights the differences between civil law and
      Islamic law in this controversial area.

PMID- 22145564
TI  - Instrumental methods to characterize molecular phospholipid films on solid
      supports.

PMID- 22145565
TI  - Using elemental ratios to predict the density of organic material composed of
      carbon, hydrogen, and oxygen.
AB  - A governing equation was developed to predict the density rho(org) of organic
      material composed of carbon, oxygen, and hydrogen using the elemental ratios O:C
      and H:C as input parameters: rho(org) = 1000 [(12 + 1(H:C) + 16(O:C)]/[7.0 +
      5.0(H:C) + 4.15(O:C)] valid for 750 < rho(org) < 1900 kg m(-3). Comparison of the
      actual to predicted rho(org) values shows that the developed equation has an
      accuracy of 12% for more than 90% of the 31 atmospherically relevant compounds
      used in the training set. The equation was further validated for secondary
      organic material (SOM) produced by isoprene photo-oxidation and by alpha-pinene
      ozonolysis. Depending on the conditions of SOM production, rho(org/SOM) ranged
      from 1230 to 1460 kg m(-3), O:C ranged from 0.38 to 0.72, and H:C ranged from
      1.40 to 1.86. Atmospheric chemistry models that simulate particle production and
      growth can employ the developed equation to simulate particle physical
      properties. The equation can also extend atmospheric measurements presented as
      van Krevelen diagrams to include estimates of the material density of particles
      and their components. Use of the equation, however, is restricted to particle
      components having negligible quantities of additional elements, most notably
      nitrogen.

PMID- 22145566
TI  - Hb H disease with various beta hemoglobinopathies: molecular, hematological and
      diagnostic aspects.
AB  - We report the molecular, hematological and diagnostic features of three Thai
      patients with Hb H (beta4) disease in combination with different beta
      hemoglobinopathies. The first case was a boy with a hitherto undescribed
      condition of Hb H-Hb Tak (HBB:c.441_442insAC) syndrome. The second case was an
      adult male with the Hb H-Hb Hope (HBB:c.410G>A) disease. The last case was a male
      patient with a combination of Hb H-Hb Constant Spring (Hb CS) (HBA2:c.427T>C) and
      a high Hbs A(2)/F beta(0)-thalassemia (beta-thal) trait (the 3.4 kb deletion). In
      all cases, no Hb H was detected and Hb H inclusion was absent, accurate diagnosis
      could be obtained after DNA analysis. All of them had mild hypochromic microcytic
      anemia with hemoglobin (Hb) values ranging from 8.8-10.4 g/dL, PCV 0.31-0.36 L/L
      and MCV 57.6-66.9 fL and none had ever received a blood transfusion. The levels
      of Hb Tak (7.8%) and Hb Hope (21.6%), respectively, observed in the first two
      cases were relatively lower than values found in heterozygotes for these two
      variants. In the last case, the level of Hb A(2) (4.8%) was within the diagnostic
      range for a beta-thal trait. The Hb F level was not elevated but a small amount
      of Hb Bart's was observed. Hematological findings and diagnostics using combined
      Hb and polymerase chain reaction (PCR) analyses are presented and compared with
      those of the other Thai patients with Hb H-beta(0)-thal, Hb H-Hb CS-Hb J-Bangkok
      (HBB:c.170G>A) and Hb H-Hb CS-Hb Pyrgos (HBB:c.251G>A) previously observed in our
      series.

PMID- 22145567
TI  - Reactive oxygen species-mediated p53 core-domain modifications determine
      apoptotic or necrotic death in cancer cells.
AB  - AIMS: p53 is known to induce apoptotic and necrotic cell death in response to
      stress, although the mechanism of these pathways is unknown. The aim of this
      study was to determine the molecular mechanism that determines p53's decision to
      select the apoptotic or necrotic mode of cell death. RESULTS: Gold nanoparticles
      (Au-NPs) induced both apoptosis and necrosis in cancer cells in a p53-dependent
      manner. In cells undergoing apoptosis and necrosis, differential patterns of
      reactive oxygen species (ROS) generation were observed that leads to the
      activation of two different sets of p53-interacting kinases and acetylases. The
      differential activation of cellular kinases and acetylases caused dissimilar
      patterns of p53 phosphorylation and acetylation. In apoptotic cells, p53 was post
      translationally modified in the core-domain, whereas in necrotic cells, it was
      modified at both N- and C-terminii, thus displaying differential DNA-binding
      activity. Au-NP10 and Au-NP80 activated fifty apoptotic and fifty nine necrotic
      p53-downstream genes, respectively. Both Au-NP10 and Au-NP80 showed HCT (p53+/+)
      tumor regression in mice xenografts. INNOVATION: This study established for the
      first time that, in cancer cells, Au-NP-mediated apoptosis and necrosis are
      controlled by differential activation of p53 and its downstream genes. Further,
      both Au-NP10 and Au-NP80 were shown to regress HCT (p53+/+) tumors via apoptotic
      and necrotic pathways, respectively. CONCLUSION: Au-NP-mediated p53 activation at
      both transcription and proteome level, through ROS-mediated p53 post
      translational modification pattern, is responsible for tumor regression, which
      may further find wider application of nanoparticles in cancer therapy.

PMID- 22145568
TI  - A tandem enyne/ring closing metathesis approach to 4-methylene-2-cyclohexenols:
      an efficient entry to otteliones and loloanolides.
AB  - A short and efficient approach to a 4-methylene-2-cyclohexenone substructure
      present in otteliones and loloanolides is described. This strategy involves a
      tandem enyne/ring closing metathesis as the key reaction to construct this labile
      core unit.

PMID- 22145569
TI  - Perinatal outcome of congenital diaphragmatic hernia in an Australian tertiary
      hospital.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is a potentially correctable
      anatomical defect that continues to represent a significant cause of stillbirth
      and neonatal death. AIMS: To describe the outcomes of fetuses diagnosed
      antenatally with CDH. METHODS: A retrospective cohort study of fetuses with CDH
      detected antenatally at our fetal medicine unit between January 1996 and December
      2008. The study analyses factors associated with mortality in a setting where no
      fetal intervention for this condition is performed. RESULTS: Eighty-six cases
      were identified and 75.5% of infants were born alive. Mortality prior to
      corrective surgery was 7%. The survival rate for babies born at term with
      isolated CDH was 83%. Presence of an additional anomaly, herniated liver and
      preterm delivery were associated with increased mortality. Seventy-four percent
      of liveborn infants with either isolated CDH or other anomalies survived to
      discharge. CONCLUSIONS: Although the overall mortality rate for this condition
      remains high, fetuses with isolated CDH born at term have relatively high
      survival rates. This study provides data for counselling parents in tertiary
      centres with advanced neonatal care but where antenatal intervention for this
      condition has not been introduced.

PMID- 22145570
TI  - Pre-synaptic dopamine D(3)  receptor mediates cocaine-induced structural
      plasticity in mesencephalic dopaminergic neurons via ERK and Akt pathways.
AB  - Exposure to psychostimulants results in neuroadaptive changes of the
      mesencephalic dopaminergic system including morphological reorganization of
      dopaminergic neurons. Increased dendrite arborization and soma area were
      previously observed in primary cultures of mesencephalic dopaminergic neurons
      after 3-day exposure to dopamine agonists via activation of D(3) autoreceptors
      (D(3) R). In this work, we showed that cocaine significantly increased dendritic
      arborization and soma area of dopaminergic neurons from E12.5 mouse embryos by
      activating phosphorylation of extracellular signal-regulated kinase (ERK) and
      thymoma viral proto-oncogene (Akt). These effects were dependent on functional
      D(3) R expression because cocaine did not produce morphological changes or
      ERK/Akt phosphorylation neither in primary cultures of D(3) R mutant mice nor
      following pharmacologic blockade with D(3) R antagonists SB-277011-A and S-33084.
      Cocaine effects on morphology and ERK/Akt phosphorylation were inhibited by pre
      incubation with the phosphatidylinositol 3-kinase inhibitor LY294002. These
      observations were corroborated in vivo by morphometrical assessment of
      mesencephalic dopaminergic neurons of P1 newborns exposed to cocaine from E12.5
      to E16.5. Cocaine increased the soma area of wild-type but not of D(3) R mutant
      mice, supporting the translational value of primary culture. These findings
      indicate a direct involvement of D3R and ERK/Akt pathways as critical mediators
      of cocaine-induced structural plasticity, suggesting their involvement in
      psychostimulant addiction.

PMID- 22145571
TI  - Single-port laparoscopic appendectomy: comparison with conventional laparoscopic
      appendectomy.
AB  - BACKGROUND: Laparoscopic appendectomy is becoming popular for the treatment of
      acute appendicitis. Since it was first described, laparoscopic appendectomy has
      been modified various times for reducing pain and improving cosmetic results.
      Single-port laparoscopic appendectomy (SPLA) may reduce more postoperative trauma
      and obtain reliable cosmetic results. We compared the safety and feasibility of
      this technique with those of conventional laparoscopic appendectomy (CLA).
      SUBJECTS AND METHODS: Between November 2008 and July 2009, 104 patients were
      enrolled in this study. Their diagnoses were performed by computed tomography
      scan. The demographic findings and surgical outcomes such as operation time,
      pathology, postoperative pain score, hospital stay, and complications of the SPLA
      group were analyzed and compared with those of the CLA group. RESULTS: SPLA was
      completed in 42 patients, and 62 patients underwent CLA. Mean age was 29.9 years
      in the CLA group and 23.9 years in the SPLA group. The average body mass index of
      patients was 23.0 kg/m(2) in the CLA group and 20.5 kg/m(2) in the SPLA group.
      Mean operation time was 55.8 minutes in the CLA group and 51.7 minutes in the
      SPLA group. There was no conversion to open appendectomy in both groups. No major
      complications were encountered in the two groups. The mean postoperative hospital
      stay was 2.9 days for the CLA group and 2.6 days for the SPLA group. There were
      no deaths in either group. CONCLUSION: SPLA is a safe technique and shows
      excellent cosmetic results. This is an easy procedure for an experienced
      laparoscopic surgeon even with conventional laparoscopic instruments. It remains
      to be evaluated in cases of perforated appendicitis and periappendiceal abscess.

PMID- 22145572
TI  - Intracorporeal knotting versus metal endoclip application for the closure of the
      appendiceal stump during laparoscopic appendectomy in uncomplicated appendicitis.
AB  - PURPOSE: The goal of the study was to compare the efficacy of two methods-
      intracorporeal knotting and metal endoclip application--for closure of the
      appendiceal stump during laparoscopic appendectomy in a specific group of
      patients with uncomplicated appendicitis. METHODS: The patients were randomized
      into two groups who had their appendiceal stump secured by intracorporeal
      knotting (Group 1) and metal endoclipping (Group 2). Primary outcome measure was
      postoperative complications, whereas secondary outcome measures were
      intraoperative complications, operative time, length of hospital stay, and re
      admissions (including rehospitalizations and reoperations). RESULTS: One hundred
      seven patients were prospectively recruited in a randomized study between
      December 2010 and May 2011. Group 1 and Group 2 included 46 and 61 patients,
      respectively. The rate of postoperative complications in Group 1 and Group 2 was
      8.7% (4/46) and 4.9% (3/61) (P>.05). There were no significant differences
      between the groups in secondary outcome measures except the mean operative time
      (61.9 minutes versus 46.3 minutes, P=.0008). CONCLUSIONS: The closure of the
      appendiceal stump by either intracorporeal knotting or metal endoclipping during
      laparoscopic appendectomy in uncomplicated appendicitis is safe with comparable
      morbidity and mortality rates.

PMID- 22145573
TI  - Transumbilical, single-port, totally extraperitoneal, laparoscopic inguinal
      hernia repair using a homemade port and a conventional instrument: an initial
      experience.
AB  - OBJECTIVE: To assess the feasibility, safety, and short-term outcome of a
      transumbilical, single-port, totally extraperitoneal (TEP) laparoscopic inguinal
      hernia repair, using a homemade port and a conventional instrument. PATIENTS AND
      METHODS: Thirty consecutive patients with inguinal hernias (including 20% with
      bilateral inguinal hernias) underwent a transumbilical, single-port, TEP
      laparoscopic hernia (LH) repair using a homemade port composed of a segment of
      corrugated anesthesia tube and a pair of surgical gloves. All operation
      procedures were done using conventional laparoscopic instruments with manually
      angled shafts in the same manner as standard multiple-port surgeries, but using
      the reverse hand technique. RESULTS: All the procedures were completed
      uneventfully and did not require additional ports. Operation times averaged 98.3
      +/- 26.7 minutes for the unilateral LH and 121.4 +/- 13.5 minutes for the
      bilateral LH. There were no perioperative complications except for 2 patients
      (7%) who developed wound seromas, which resolved after conservative treatment. No
      hernia recurred during the 6-month follow-up. CONCLUSION: A transumbilical,
      single-port, TEP laparoscopic hernioplasty using a homemade port and a
      conventional instrument permitted nearly scarless surgery for the treatment of
      inguinal hernias. Further studies are necessary before this approach can be
      recommended as a standard procedure.

PMID- 22145574
TI  - Retrospective comparison of laparoscopic partial nephrectomy versus laparoscopic
      renal cryoablation for small (<3.5 cm) cortical renal masses.
AB  - OBJECTIVE: We compared perioperative and short-term outcomes of renal
      laparoscopic partial nephrectomy (LPN) and laparoscopic cryoablation (LCA) in
      patients with small (<3.5 cm) renal cortical neoplasms. METHODS: A retrospective
      analysis from our prospectively established database was performed. We identified
      92 patients with 95 lesions treated with LPN and 75 patients with 91 lesions
      treated with LCA. RESULTS: The LPN and LCA groups were comparable in mean tumor
      size and preoperative and postoperative creatinine level (P=.495, P=.953, and
      P=.101) respectively. Patients undergoing LPN were younger in age (58.8 versus
      69.2 years, P<.001), had a higher mean estimated blood loss (168.4 versus 6  mL,
      P=.005), and had a prolonged mean operative time (151.6 versus 128.6 minutes,
      P=.01). Six complications occurred in the LCA group and 11 in the LPN group. The
      median follow-up time was 21.8 months for LPN and 14 months for LCA (P<.001). Two
      recurrences were detected in the LCA group, and 1 recurrence was reported after
      LPN. CONCLUSIONS: In the treatment of small renal cortical neoplasms with short
      term follow-up, LPN and LCA seem to be equally effective. LCA offers decreased
      blood loss, shorter operative time, and less morbidity. Longer follow-up is
      required to establish oncologic efficacy.

PMID- 22145576
TI  - Existence of a new emitting singlet state of proflavine: femtosecond dynamics of
      the excited state processes and quantum chemical studies in different solvents.
AB  - Proflavine (3,6-diaminoacridine) shows fluorescence emission with lifetime, 4.6
      +/- 0.2 ns, in all the solvents irrespective of the solvent polarity. To
      understand this unusual photophysical property, investigations were carried out
      using steady state and time-resolved fluorescence spectroscopy in the pico- and
      femtosecond time domain. Molecular geometries in the ground and low-lying excited
      states of proflavine were examined by complete structural optimization using ab
      initio quantum chemical computations at HF/6-311++G** and CIS/6-311++G** levels.
      Time dependent density functional theory (TDDFT) calculations were performed to
      study the excitation energies in the low-lying excited states. The steady state
      absorption and emission spectral details of proflavine are found to be influenced
      by solvents. The femtosecond fluorescence decay of the proflavine in all the
      solvents follows triexponential function with two ultrafast decay components
      (tau(1) and tau(2)) in addition to the nanosecond component. The ultrafast decay
      component, tau(1), is attributed to the solvation dynamics of the particular
      solvent used. The second ultrafast decay component, tau(2), is found to vary from
      50 to 215 ps depending upon the solvent. The amplitudes of the ultrafast decay
      components vary with the wavelength and show time dependent spectral shift in the
      emission maximum. The observation is interpreted that the time dependent spectral
      shift is not only due to solvation dynamics but also due to the existence of more
      than one emitting state of proflavine in the solvent used. Time resolved area
      normalized emission spectral (TRANES) analysis shows an isoemissive point,
      indicating the presence of two emitting states in homogeneous solution. Detailed
      femtosecond fluorescence decay analysis allows us to isolate the two independent
      emitting components of the close lying singlet states. The CIS and TDDFT
      calculations also support the existence of the close lying emitting states. The
      near constant lifetime observed for proflavine in different solvents is suggested
      to be due to the similar dipole moments of the ground and the evolved emitting
      singlet state of the dye from the Franck-Condon excited state.

PMID- 22145577
TI  - Does octreotide prevent L-asparaginase-associated pancreatitis in children with
      acute lymphoblastic leukaemia?

PMID- 22145575
TI  - Hot spot analysis for driving the development of hits into leads in fragment
      based drug discovery.
AB  - Fragment-based drug design (FBDD) starts with finding fragment-sized compounds
      that are highly ligand efficient and can serve as a core moiety for developing
      high-affinity leads. Although the core-bound structure of a protein facilitates
      the construction of leads, effective design is far from straightforward. We show
      that protein mapping, a computational method developed to find binding hot spots
      and implemented as the FTMap server, provides information that complements the
      fragment screening results and can drive the evolution of core fragments into
      larger leads with a minimal loss or, in some cases, even a gain in ligand
      efficiency. The method places small molecular probes, the size of organic
      solvents, on a dense grid around the protein and identifies the hot spots as
      consensus clusters formed by clusters of several probes. The hot spots are ranked
      based on the number of probe clusters, which predicts the binding propensity of
      the subsites and hence their importance for drug design. Accordingly, with a
      single exception the main hot spot identified by FTMap binds the core compound
      found by fragment screening. The most useful information is provided by the
      neighboring secondary hot spots, indicating the regions where the core can be
      extended to increase its affinity. To quantify this information, we calculate the
      density of probes from mapping, which describes the binding propensity at each
      point, and show that the change in the correlation between a ligand position and
      the probe density upon extending or repositioning the core moiety predicts the
      expected change in ligand efficiency.

PMID- 22145578
TI  - Tailored skills training for practitioners to enhance assessment of prognostic
      factors for persistent and disabling back pain: four quasi-experimental single
      subject studies.
AB  - The well-known gap between guidelines and behaviour in clinical practice calls
      for effective behaviour change interventions. One example showing this gap is
      physiotherapists' insufficient assessment of psychosocial prognostic factors in
      back pain (i.e., yellow flags). The present study aimed to evaluate an
      educational model by performing a tailored skills training intervention for
      caregivers and studying changes over time in physiotherapists' assessment of
      prognostic factors in telephone consultations. A quasi-experimental single
      subject design over 36 weeks was used, with repeated measurements during
      baseline, intervention, and postintervention phases. Four physiotherapists in
      primary health care audiorecorded a total of 63 consultations with patients. The
      tailored intervention included individual goal setting, skills training, and
      feedback on performance. The primary outcome was the number of assessed
      prognostic factors (0-10). Changes were seen in all four participants. The amount
      of assessed prognostic factors increased from between 0 and 2 at baseline to
      between 6 and 10 at postintervention. Time spent on assessment of psychosocial
      factors increased, and time spent on discussions about biomedical pain symptoms
      decreased. Knowledge and biopsychosocial attitudes toward back pain were
      congruent with guidelines at inclusion and did not change markedly during the
      intervention. Self-efficacy for assessment of cognitive and emotional prognostic
      factors increased during the study phases. The results suggest that a tailored
      skills training intervention using behaviour change techniques, such as
      individual goal setting, skills training, and feedback on performance, is
      effective in producing change in specific clinical behaviours in
      physiotherapists.

PMID- 22145580
TI  - ZEN and the art of breast health maintenance.
AB  - Zearalenone (ZEN) is a non-steroidal mycoestrogen that widely contaminates
      agricultural products. ZEN and its derivatives share similar molecular mechanisms
      and activity with estrogens and interact with ERalpha and ERbeta leading to
      changes in the reproductive system in both animals and humans. The reduced form
      of ZEN, alpha-ZEA ralenol, has been used as an anabolic agent for animals and
      also proposed as hormonal replacement therapy in postmenopausal women.
      Furthermore, both zearelanol ZEN and derivatives have been patented as oral
      contraceptives. ZEN has been widely used in the United States since 1969 to
      improve fattening rates in cattle by increasing growth rate and feed conversion
      efficiency. Evidence of human harm from this practice is provided by observations
      of central precocious puberty. As a result, this practice has been banned by the
      European Union. As ZEN has been associated with breast enlargement in humans, it
      has been included in many bust-enhancing dietary supplements but epidemiological
      evidence is lacking with regard to breast cancer risk. Extensive work with human
      breast cancer cell lines has shown estrogenic stimulation in those possessing ER
      but a reduction in DMBA-induced breast cancers in rodents given ZEN. Protein
      disulfide isomerase provides a molecular biomarker of dietary exposure to ZEN and
      its derivatives allowing the detection and control of harmful food intake. The
      interaction of ZEN with anti-estrogens, anticancer agents and antioxidants
      requires further investigation.

PMID- 22145579
TI  - Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes.
AB  - BACKGROUND: Phosphatidylcholine (PPC) formulation is used for lipolytic
      injection, even though its mechanism of action is not well understood. METHODS:
      The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was
      measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD), and
      a PPC formulation. Western blot analysis was performed to examine PPC-induced
      signaling pathways. RESULTS: PPC, SD, and PPC formulation significantly decreased
      3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not
      cytotoxic to CCD-25Sk human fibroblasts at concentrations <1 mg/ml, whereas SD
      and PPC formulation were cytotoxic. Western blot analysis demonstrated that PPC
      alone led to the phosphorylation of the stress signaling proteins, such as p38
      mitogen-activated protein kinase and c-Jun N-terminal kinase, and activated
      caspase-9, -8, -3 as well as cleavage of poly(ADP-ribose) polymerase. However, SD
      did not activate the apoptotic pathways. Instead, SD and PPC formulation induced
      cell membrane lysis, which may lead to necrosis of cells. CONCLUSIONS: PPC
      results in apoptosis of 3T3-L1 cells.

PMID- 22145582
TI  - Simulation of future global warming scenarios in rice paddies with an open-field
      warming facility.
AB  - To simulate expected future global warming, hexagonal arrays of infrared heaters
      have previously been used to warm open-field canopies of upland crops such as
      wheat. Through the use of concrete-anchored posts, improved software, overhead
      wires, extensive grounding, and monitoring with a thermal camera, the technology
      was safely and reliably extended to paddy rice fields. The system maintained
      canopy temperature increases within 0.5 degrees C of daytime and nighttime set
      point differences of 1.3 and 2.7 degrees C 67% of the time.

PMID- 22145581
TI  - Association of the TRIB1 tribbles homolog 1 gene rs17321515 A>G polymorphism and
      serum lipid levels in the Mulao and Han populations.
AB  - BACKGROUND: The association of rs17321515 single nucleotide polymorphism (SNP)
      near TRIB1 gene and serum lipid profiles has never been studied in the Chinese
      population. Therefore, the present study was undertaken to detect the association
      of rs17321515 SNP and several environmental factors on serum lipid levels in the
      Mulao and Han populations. METHODS: A total of 639 unrelated subjects of Mulao
      nationality and 644 participants of Han nationality were randomly selected from
      our previous stratified randomized cluster samples. Genotypes of the TRIB1
      rs17321515 A>G SNP were determined via polymerase chain reaction and restriction
      fragment length polymorphism, and then confirmed by direct sequencing. RESULTS:
      Serum apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.05).
      There were no differences in the genotypic and allelic frequencies between the
      two ethnic groups (P > 0.05). High- and low-density lipoprotein cholesterol (HDL
      C and LDL-C) levels in Han were different among the genotypes (P < 0.05 for
      each), the subjects with AG/GG genotypes had higher HDL-C and LDL-C levels than
      the subjects with AA genotype. Total cholesterol (TC), HDL-C, LDL-C, ApoA1 and
      ApoB levels in Han males were different among the genotypes (P < 0.05-0.001), the
      G carriers had higher TC, HDL-C, LDL-C, ApoA1 and ApoB levels than the G
      noncarriers. HDL-C levels in Mulao males were different among the genotypes (P <
      0.05), the G carriers had lower HDL-C levels than the G noncarriers. Serum HDL-C
      and LDL-C levels in both ethnic groups and TG levels in Han were correlated with
      the genotypes or alleles (P < 0.05-0.01). TG and HDL-C levels in Mulao males and
      TG, HDL-C, LDL-C and ApoA1 levels in Han males were correlated with genotypes or
      alleles (P < 0.05-0.001). TG and ApoA1 levels in Han females were associated with
      genotypes (P < 0.05 for each). Serum lipid parameters were also associated with
      several environmental factors in both ethnic groups. CONCLUSIONS: The
      associations of TRIB1 rs17321515 SNP and serum lipid levels are different between
      the Mulao and Han populations. These discrepancies might partly result from
      different TRIB1 gene-environmental interactions in both ethnic groups.

PMID- 22145583
TI  - The target-specific transporter and current status of diuretics as
      antihypertensive.
AB  - The currently available diuretics increase the urinary excretion of sodium
      chloride by selective inhibition of specific sodium transporters in the loop of
      Henle and distal nephron. In recent years, the molecular cloning of the diuretic
      sensitive sodium transporters at distal convoluted tubule has improved our
      understanding of the cellular mechanisms of action of each class of diuretics.
      Diuretics are tools of considerable therapeutic importance. First, they
      effectively reduce blood pressure. Loop and thiazide diuretics are secreted from
      the proximal tubule via the organic anion transporter-1 and exert their diuretic
      action by binding to the Na(+)-K(+)-2Cl(-) co-transporter type 2 in the thick
      ascending limb and the Na(+)-Cl(-) co-transporter in the distal convoluted
      tubule, respectively. Recent studies in animal models suggest that abundance of
      these ion transporters is affected by long-term diuretic administration. The
      WHO/ISH guidelines point out that diuretics enhance the efficacy of
      antihypertensive drugs and will most often be a component of combination therapy.

PMID- 22145584
TI  - Physico-chemical approach to targeting phenomena.

PMID- 22145585
TI  - Synthesis and antibacterial activity of novel 4-chloro-2
      mercaptobenzenesulfonamide derivatives.
AB  - Few series of novel 4-chloro-2-mercaptobenzenesulfonamides have been synthesized
      by the reactions of N-(benzenesulfonyl)cyanamide potassium salts 7-15 with
      corresponding hydrazinecarbodithioic acid esters, 1-substituted carbothioic acid
      hydrazides, methyl 3-aminothiophene-2-carboxylate, methyl 2-aminobenzoate, 2
      aminophenol or 2-aminothiophenol. The synthesized compounds (16-49) were screened
      in vitro for their antibacterial activity. Some of the tested compounds 16, 17,
      23, 24, 31, 32 and 48 showed the promising activity against many of anaerobic
      Gram-positive bacteria strains.

PMID- 22145586
TI  - Synthesis and pharmacological evaluation of novel arginine analogs as potential
      inhibitors of acetylcholine-induced relaxation in rat thoracic aortic rings.
AB  - It is widely appreciated that the vascular endothelium is capable of modulating
      vascular smooth muscle tone suiting it well for its role as an important
      regulator of a number of diverse biological processes. Endothelial dysfunction is
      an early manifestation of atherothrombosis and a consequence of the established
      disease. Although several arginine derivatives alkylated at one of the guanidino
      nitrogen were found to inhibit vasorelaxation induced by acetylcholine, activity
      of the corresponding arginine esters is not reported. The present work was
      therefore designed to synthesize and evaluate series of novel arginine
      derivatives to obtain further insight into structure-activity relationship in
      this series of compounds. Present study involves assessment of activity of these
      novel compounds on the vascular tone of rat thoracic aorta in comparison with l
      arginine analog, that is, l-nitro-arginine methyl ester (l-NAME). Results from
      the present study showed that full reversal of phenylephrine-mediated contraction
      was achieved by cumulative applications of acetylcholine (3nm-300MUm), which were
      abolished when the aortic rings were pretreated with l-NAME (300MUm). Results
      from the present study demonstrated that these novel arginine derivatives cause
      significant yet reversible reduction in acetylcholine-mediated relaxation,
      similar to that of L-NAME.

PMID- 22145587
TI  - Recent advances in Schistosoma genomics.
AB  - Schistosome research has entered the genomic era with the publications reporting
      the Schistosoma mansoni and Schistosoma japonicum genomes. Schistosome genomics
      is motivated by the need for new control tools. However, much can also be learned
      about the biology of Schistosoma, which is a tractable experimental model. In
      this article, we review the recent achievements in the field of schistosome
      research and discuss future perspectives on genomics and how it can be integrated
      in a usable format, on the genetic mapping and how it has improved the genome
      assembly and provided new research approaches, on how epigenetics provides
      interesting insights into the biology of the species and on new functional
      genomics tools that will contribute to the understanding of the function of
      genes, many of which are parasite- or taxon specific.

PMID- 22145588
TI  - Editorial Comment to Cruciferous vegetables intake and risk of prostate cancer: a
      meta-analysis.

PMID- 22145589
TI  - Transcriptome analysis of Stagonospora nodorum: gene models, effectors,
      metabolism and pantothenate dispensability.
AB  - The wheat pathogen Stagonospora nodorum, causal organism of the wheat disease
      Stagonospora nodorum blotch, has emerged as a model for the Dothideomycetes, a
      large fungal taxon that includes many important plant pathogens. The initial
      annotation of the genome assembly included 16,586 nuclear gene models. These gene
      models were used to design a microarray that has been interrogated with labelled
      transcripts from six cDNA samples: four from infected wheat plants at time points
      spanning early infection to sporulation, and two time points taken from growth in
      artificial media. Positive signals of expression were obtained for 12,281 genes.
      This represents strong corroborative evidence of the validity of these gene
      models. Significantly differential expression between the various time points was
      observed. When infected samples were compared with axenic cultures, 2882 genes
      were expressed at a higher level in planta and 3630 were expressed more highly in
      vitro. Similar numbers were differentially expressed between different
      developmental stages. The earliest time points in planta were particularly
      enriched in differentially expressed genes. A disproportionate number of the
      early expressed gene products were predicted to be secreted, but otherwise had no
      obvious sequence homology to functionally characterized genes. These genes are
      candidate necrotrophic effectors. We have focused attention on genes for
      carbohydrate metabolism and the specific biosynthetic pathways active during
      growth in planta. The analysis points to a very dynamic adjustment of metabolism
      during infection. Functional analysis of a gene in the coenzyme A biosynthetic
      pathway showed that the enzyme was dispensable for growth, indicating that a
      precursor is supplied by the plant.

PMID- 22145590
TI  - Noncoeliac enteropathy: the differential diagnosis of villous atrophy in
      contemporary clinical practice.
AB  - BACKGROUND: Duodenal villous atrophy (DVA) is a key diagnostic finding in coeliac
      disease (CD). However, the differential diagnosis for this finding is broad. AIM:
      To identify conditions causing noncoeliac enteropathy (NCE) with villous atrophy
      and methods to differentiate between CD and NCE in clinical practice. METHODS:
      Through record review we identified patients with DVA due to conditions other
      than CD. Patient demographics, clinical features and relevant investigations were
      compared with CD patients. Rates of CD misdiagnosis, and response to treatments
      were recorded. RESULTS: Thirty cases of NCE were identified with ten different
      aetiologies. Unspecified immune-mediated enteropathy was the most common
      aetiology; affecting 10 patients. Gastrointestinal symptoms were more common in
      NCE than those in CD patients (P < 0.01). Twenty of the 24 NCE patients tested
      were HLA-DQ2/DQ8 negative. Twenty-six NCE patients were negative for IgA tissue
      transglutaminase (tTG) (P = 0.0001). Intraepithelial lymphocytosis was absent in
      10 (33.3%) patients. Twenty-one NCE patients initially misdiagnosed with CD and
      one with gluten intolerance were prescribed a gluten free diet (GFD). Fifteen of
      22 had repeat biopsy and none showed histological improvement. CONCLUSIONS:
      Although coeliac disease is the most common cause of DVA, noncoeliac enteropathy
      is not rare and may easily be mistaken for coeliac disease. Noncoeliac
      enteropathy is suggested by a normal initial tTG (87%), lack of intraepithelial
      lymphocytosis on biopsy, and lack of histological response to a gluten free diet.
      Subjective response to gluten free diet has poor predictive value for coeliac
      disease. Noncoeliac enteropathy can often be confirmed by negative HLA-DQ2/DQ8
      testing and targeted investigations can ascertain a definitive aetiology in most
      cases.

PMID- 22145591
TI  - Updates on "endoplasmic reticulum redox".

PMID- 22145595
TI  - Synthesis of new indole-2-carboxamide and 3-acetamide derivatives and evaluation
      their antioxidant properties.
AB  - In recent years, antioxidant compounds play an important role as a health
      protecting factor. Antioxidants protect cells against the damaging effects of
      reactive oxygen species (ROS). An imbalance between antioxidants and ROS results
      in oxidative stress, which leads to cellular damage and it is linked to many
      vital diseases. It was shown that heme oxygenase (HO) provides efficient
      cytoprotection against oxidative stress. In this study, a series of indole-2
      carboxamide and 3-acetamide derivatives was tested for in vitro effects on HO
      activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition. Among the
      synthesized compounds, N-[3-(dimethylamino)propyl]-1H-indole-2-carboxamide 3 was
      found as the most activator of HO and N-(2-(dimethylamino)ethyl)-2-(1H-indol-3
      yl)acetamide 8 was found the most potent inhibitor for DPPH at 10(-4) M
      concentration.

PMID- 22145596
TI  - Laparoscopic appendectomy: vascular control of the appendicular artery using
      monopolar cauterization versus clips.
AB  - INTRODUCTION: Laparoscopic appendectomy is now the standard of treatment for
      acute appendicitis in medical centers where advanced minimally invasive surgery
      is performed, and it has become the standard of care in our institution. The
      techniques for laparoscopic appendectomy are widely described in surgical
      textbooks, but the vascular control of the appendicular artery is diverse. In
      this article, we compare the benefits and possible complications of different
      techniques to obtain vascular control. SUBJECTS AND METHODS: This is a
      retrospective study of prospectively collected data including all cases of
      laparoscopic appendectomy from September 1990 to August 2009. Here we describe
      the different methods used, and we present a large series of 729 cases of
      laparoscopic appendectomy. In the majority of the cases the diagnosis was acute
      appendicitis followed by laparoscopic appendectomy. In only 124 cases was an
      incidental appendectomy performed associated with another laparoscopic procedure.
      RESULTS: In 350 cases (48%) monopolar cauterization was used to obtain vascular
      control of the appendicular artery. In the other 379 cases the artery was either
      clipped or stapled (52%). There were no postoperative complications reported.
      There was no difference in patient outcome with either approach to obtain
      adequate vascular control. CONCLUSIONS: The vascular control of the appendicular
      artery obtained with monopolar cautery is a safe, fast, and economic approach
      easily done during a laparoscopic or needlescopic appendectomy with no increased
      risks or complications.

PMID- 22145597
TI  - The questions of science always lie in what is not known yet, though the
      techniques we use determine what questions we can study.

PMID- 22145598
TI  - Analytical value of detecting an individual molecular binding event: the case of
      the surface plasmon resonance biosensor.
AB  - We explore the ultimate limits of the performance of bioanalytical approaches
      based on the detection of individual molecular binding events taking place at the
      sensor surface interfaced with a microfluidic flow-through cell. As a case study,
      we investigate and compare the bioanalytical performance of flow-through surface
      plasmon resonance (SPR) sensors based on (1) localized surface plasmons (LSP)
      which detect a single binding event and (2) propagating surface plasmons (PSP)
      which integrate a great number of simultaneously occurring binding events. We
      demonstrate that for the biomolecular interactions most relevant to biosensing
      the single-binding-event LSP approach is inferior to the integrating PSP
      approach. We estimate that the number of biorecognition elements available to
      interact with the analyte molecules would need to be, depending on the size of
      the analyte and parameters of the molecular interaction, in the order of 10 to
      10(3) to increase the probability of the positive response of the LSP-based
      sensor to that of the PSP-based sensor.

PMID- 22145599
TI  - Successful outcome of flexible ureteroscopy with holmium laser lithotripsy for
      renal stones 2 cm or greater.
AB  - Although percutaneous nephrolithotomy has been recommended as the first-line
      treatment for renal stones larger than 2 cm, its major complication rate is not
      negligible and less invasive approaches are to be explored. Thanks to the recent
      advances in endoscopic technology, flexible ureteroscopy has become another
      option in this setting. Herein we report our most recent experience with flexible
      ureteroscopy for large renal stones. Between September 2008 and May 2011, 20
      patients with renal stones >= 2 cm underwent a total of 28 procedures of
      ureteroscopy with holmium laser lithotripsy, using the Olympus URF-P5 and a
      ureteral access sheath. The number of procedures, operative time, stone-free
      rates, stone compositions and complications were evaluated. Stone-free status was
      defined as the absence of fragments or fragments of <= 4 mm. Mean stone size was
      3.1 cm (range 2.0-5.0). The average number of procedures was 1.4. One, two and
      three procedures were required in 13, six and one patients, respectively.
      Overall, the stone-free rate was 90%. The stone-free rate for preoperative stone
      size of 2 to <= 4 cm and >4 cm was 100% (14/14) and 67% (4/6), respectively. No
      major intraoperative complications were identified. Postoperative high-grade
      fever was observed in three patients, including one patient who developed sepsis.
      All these patients were successfully treated conservatively. Our findings suggest
      that ureteroscopy represents a favorable option for selected patients with renal
      stones, especially those 2 to <= 4 cm in size.

PMID- 22145600
TI  - High-amylose rice improves indices of animal health in normal and diabetic rats.
AB  - A high-amylose rice with 64.8% amylose content (AC) was developed by transgenic
      inhibition of two isoforms of starch branching enzyme (SBE), SBEI and SBEIIb, in
      an indica rice cultivar. The expression of SBEI and SBEIIb was completely
      inhibited in the transgenic line, whereas the expression of granule-bound starch
      synthase was normal. Compared with wild-type rice, drastic reductions in both
      SBEs in the transgenic rice increased apparent AC in flour from 27.2% to 64.8%,
      resistant starch (RS) content from 0% to 14.6% and total dietary fibre (TDF) from
      6.8% to 15.2%. Elevated AC increased the proportion of long unit chains in
      amylopectin and increased onset gelatinization temperature and resistance to
      alkaline digestion; however, kernel weight was decreased. A rat feeding trial
      indicated that consumption of high-amylose rice decreased body weight gain
      significantly (P < 0.01); increased faecal mass, faecal moisture and short-chain
      fatty acids; and lowered the faecal pH. An acute oral rice tolerance test
      revealed that the high-amylose rice had a positive effect on lowering the blood
      glucose response in diabetic Zucker fatty rats. This novel rice with its high AC,
      RS and TDF offers potential benefits for its use in foods and in industrial
      applications.

PMID- 22145601
TI  - Oxidative stress mediates cardiac infarction aggravation induced by intermittent
      hypoxia.
AB  - We have previously shown that chronic intermittent hypoxia (IH), a component of
      the obstructive sleep apnea syndrome, increases heart sensitivity to infarction.
      We investigate here the deleterious mechanisms potentially involved in the IH
      induced infarction aggravation, investigating the role of oxidative stress. Male
      Wistar rats were subjected to chronic IH or normoxia (N). IH consisted of
      repetitive 1-min cycles (30 s with inspired O2 fraction 5% followed by 30 s
      normoxia) and was applied for 8 h during daytime, for 14 days. After the 14-day
      exposure, mean arterial blood pressure (MABP) was higher in the hypoxic compared
      with the normoxic group. Infarct size, measured on isolated hearts after ischemia
      reperfusion, was significantly increased in IH compared with normoxic group (36.0
      +/- 2.8% vs. 21.8 +/- 3.1% for tempol corresponding control groups and 40.3 +/-
      3.5% vs. 29.4 +/- 3.7% for melatonin corresponding control groups). Tempol or
      melatonin administration during the 14-day IH exposure prevented both IH-induced
      increase in MABP and infarction aggravation (24.8 +/- 2.8% vs. 25.9 +/- 4.0% for
      tempol-treated groups and 32.3 +/- 3.2% vs. 34.5 +/- 4.2% for melatonin-treated
      groups). Myocardial oxidative stress was induced by IH, as measured by
      dihydroethidium (DHE) level and p47-phox expression (the cytosolic protein
      required for the activation of the NADPH oxidase). This effect was abolished by
      tempol and melatonin treatments, which were able to normalize DHE level and NADPH
      expression. In conclusion, oxidative stress appears to mediate the deleterious
      cardiovascular effects of IH and, in particular, the increased myocardial
      susceptibility to infarction.

PMID- 22145602
TI  - Salinomycin: a new cancer drug candidate.
AB  - Very recently, it has been shown that it is possible to selectively kill breast
      cancer stem cells using the ionophore antibiotic, salinomycin. Its ability to
      kill cancer stem cells and apoptosis-resistant cancer cells may define
      salinomycin as a novel anticancer drug.

PMID- 22145604
TI  - The management of missed miscarriage in an outpatient setting: 800 versus 600 MUg
      of vaginal misoprostol.
AB  - BACKGROUND: Many misoprostol regimens have been used to treat early pregnancy
      loss as an alternative to surgical evacuation, with differing adverse event and
      success rates. AIMS: This study sought to compare the effectiveness and adverse
      effects of 800 and 600 MUg of misoprostol administered vaginally for the
      treatment of early pregnancy failure in an outpatient setting. METHODS: A
      retrospective, observational study of 946 women with a missed miscarriage <12
      weeks' gestation was performed: 487 women received 800 MUg (group 1) and 459
      women received 600 MUg (group 2) of vaginal misoprostol every 24 h for two days.
      The first follow-up was seven days after treatment. Women were asked about
      symptoms, and a transvaginal ultrasound was performed. If an incomplete
      miscarriage or gestational sac was still found, then an additional dose of
      intravaginal misoprostol was prescribed, and a second follow-up visit was
      arranged for seven days later. Surgical evacuation was scheduled for women who
      did not wish to continue medical treatment after the first or second follow-up
      visit. RESULTS: The total rate of complete miscarriage was 90.6% after 800 MUg
      and 87.8% after 600 MUg of intravaginal misoprostol. The percentage of women who
      underwent surgical evacuation after medical treatment was 9.4% for group 1 and
      12.2% for group 2. CONCLUSIONS: Complete uterine evacuation after a missed
      miscarriage was effectively induced by both 600 and 800 MUg of misoprostol. The
      overall success of medical treatment with intravaginal misoprostol demonstrates
      that the treatment is safe in an outpatient setting.

PMID- 22145605
TI  - The use of a single Hem-o-lok clip in securing the base of the appendix during
      laparoscopic appendectomy.
AB  - BACKGROUND: During laparoscopic appendectomy, the standard technique in securing
      the base of the appendix is by endoloop ligatures or a stapler. We earlier
      demonstrated the possibility of the application of a double Hem-o-lok((r)) clip
      in securing of the base of the appendix. The application of only one plastic clip
      would, however, lower the cost of the laparoscopic procedure even further and
      shorten the surgery time. The objective of this prospective study was to evaluate
      the possible advantages of securing of the base of the appendix using only one
      Hem-o-lok clip. PATIENTS AND METHODS: The 90 patients with acute appendicitis
      were randomly divided into three groups: In the first group, the base of the
      appendix was secured using one endoloop ligature, in the second group using a 45
      mm stapler, and in the third group using only one nonabsorbable Hem-o-lok clip.
      The data collected included age, gender, surgery time, time of
      endoloop/stapler/clip application, hospital stay, costs associated with these,
      and intra- and postoperative complications. RESULTS: There were no significant
      differences in hospital stay among the three groups of patients; but the average
      time of the operation was significantly longer in the endoloop group than in the
      stapler group (P=.002), whereas the endoloop and Hem-o-lok groups were not
      statistically different (P=.22). The time of application of the endoloop was
      significantly longer than for the stapler (P<.0001) and Hem-o-lok (P<.0001)
      groups. The time of application of the stapler was significantly shorter than
      that of the Hem-o-lok (P<.0001). However, the price of one endoloop is ?28.85,
      for the stapler is ?230.7, and for one Hem-o-lok clip is ?2.35. CONCLUSION: The
      use of one Hem-o-lok clip is as safe as an endoloop and/or stapler; however, the
      time of the laparoscopic procedure using the Hem-o-lok was shorter in comparison
      with the use of an endoloop, with the cost of the procedure being the lowest.

PMID- 22145606
TI  - Laparoscopic choledochoduodenostomy for biliary stone disease: a single-center 10
      year experience.
AB  - BACKGROUND AND AIMS: Patients with a dilated common bile duct (CBD) and multiple,
      primary, or recurrent stones are candidates for choledochoduodenostomy. This
      article reviews our technique and results of laparoscopic choledochoduodenostomy
      (LCDD) in patients with CBD stones. SUBJECTS AND METHODS: Prospectively
      maintained data of patients with a dilated CBD and multiple, primary, or
      recurrent CBD stones who underwent LCDD after laparoscopic CBD exploration
      (LCBDE) at a tertiary-care teaching hospital in New Delhi, India, during a 10
      year period from April 2001 to March 2011 were analyzed. RESULTS: During this
      period, of 195 patients who underwent LCBDE for CBD stones, 27 patients underwent
      LCDD. The mean age of patients was 45.7+/-13.5 years. There were 6 male and 21
      female patients. Sixteen (59.2%) patients had jaundice at presentation. Average
      CBD diameter was 19.6+/-4.4 mm. On average, 11.5+/-15.7 stones were removed from
      the CBD. Mean operative time was 156.3+/-25.4 minutes. Mean operative blood loss
      was 143.3+/-85.5 mL. Average postoperative hospital stay was 6.4+/-3.8 days. CBD
      clearance was obtained in all cases. One patient had a bile leak that resolved
      with conservative treatment. There was no mortality. No patient has had
      recurrence of symptoms or cholangitis after a follow-up of up to 9 years.
      CONCLUSION: LCDD can be safely performed in patients with a large stone burden
      and recurrent or primary CBD stones. Although it requires advanced laparoscopic
      skills, the benefits of a single-stage laparoscopic procedure can be extended to
      these patients safely with good results.

PMID- 22145607
TI  - Mapping the maze of minimally invasive surgery simulators.
AB  - BACKGROUND: Conforming to, among other considerations, legal and ethical concerns
      for patient safety, there is an increasing demand to assess a surgeon's skills
      prior to performance in the operating room in pursuit of higher-quality
      treatment. Training in minimally invasive surgery (MIS) must therefore be
      intensified, including team training. New methods to train and assess minimally
      invasive surgical skills are gaining interest. The goal of this review is to
      provide instructors with an overview of available MIS training tools. In this
      review, we discuss currently available simulators for MIS training.
      Applicability, validity, and construction of simulators are reviewed. Also, some
      of the leading training programs and assessment methods in MIS are reviewed.
      METHODS: A literature search was performed on studies evaluating surgical task
      performance on a simulator, reviewing satisfaction with laparoscopic training
      programs, or validating simulators or assessment methods. RESULTS: Simulators may
      be divided into simple box trainers and computer-based systems, such as virtual
      and augmented simulators. All have advantages and disadvantages. An overview is
      provided of currently available training systems, validity, trainee assessment,
      and the importance of training programs in MIS. CONCLUSIONS: No simulator yet
      provides the ability to train the entire set of required psychomotor skills or
      procedures for MIS. A multiyear training program combining various simulators for
      multiple-level training, including team training, should be constructed.

PMID- 22145608
TI  - Water-filled laparoendoscopic surgery (WAFLES): feasibility study in porcine
      model.
AB  - PURPOSE: Recent surgical techniques have been advancing under endoscopic view and
      insufflation of carbon dioxide gas to expand the abdominal cavity. Isotonic fluid
      could be one candidate for expanding cavities to facilitate surgical maneuvering.
      We tested the feasibility and drawbacks of replacement of irrigating materials
      using a porcine model (water-filled laparoendoscopic surgery [WAFLES]). MATERIALS
      AND METHODS: Laparoscopic cholecystectomy was performed in two porcine models
      using instillation of sorbitol solution as irrigant. Solution irrigation was
      performed through one of four ports, with drainage via another port. Conventional
      forceps equipped with a monopolar electrode for electrocautery, laparoscope,
      video processor, ultrasound, and transducer for measuring intraabdominal pressure
      were used. RESULTS: Laparoscopic cholecystectomy was successfully undertaken with
      the following benefits: (1) clear observation of the dissecting plane throughout
      maneuvering; (2) control of oozing and spilled bile by irrigation and suction;
      and (3) ultrasonographic and laparoscopic images can be obtained simultaneously
      without any restriction to probe location. However, two disadvantages should be
      noted: (1) difficulties in managing floating organs and (2) interruption of
      vision by blood. CONCLUSIONS: WAFLES provides some benefits for endoscopic
      surgery with proper devices, including apparatuses for irrigation and suction.
      Efficient irrigation and selection of proper irrigant and apparatuses are
      required to establish an acceptable procedure.

PMID- 22145609
TI  - A new in vivo method for testing closures of gastric NOTES incisions using leak
      of the closure or gastric yield as endpoints.
AB  - BACKGROUND: We developed a non-survival in vivo model for testing of gastric
      natural orifice translumenal endoscopic surgery (NOTES) closures based on the
      gastric yield pressure. The aim of this study was to test our model comparing
      different endoscopic closure techniques with surgical closure of a NOTES gastric
      incision. METHODS: Laparotomy was performed in 30 pigs. One tube for air
      inflation and one manometry tube were inserted into the stomach via the pylorus,
      which was closed gas-tight, and the abdominal wall was closed. The stomach was
      inflated with air, and the gastroesophageal yield pressure was measured. A
      gastroscopy was performed, and a standard NOTES access was created followed by
      randomization to closure by surgical suturing, T-tags, Padlock-G over-the-scope
      (OTS)-clips, OVESCO OTS-clips, and traditional clips. All closures were tested
      twice with air insufflation. Gastric yield pressure or leak pressure of each
      closure was recorded. RESULTS: The mean baseline gastric yield pressure was 80.5
      mm Hg. Post-closure yield pressure was 79.9 mm Hg. Leak test results after
      closure were as follows: surgery, 0/6 leaked; T-tags, 1/6 leaked before reaching
      yield pressure (56 mm Hg); Padlock-G, 2/5 leaked (71.5 mm Hg); OVESCO OTS-clips,
      3/6 leaked (27.2 mm Hg); and traditional clips, 5/6 leaked (27.2 mm Hg). TAS T
      tags and surgical closures leaked significantly less than the other groups
      (P=.01). Traditional clips and OVESCO OTS-clips leaked at significantly lower
      pressures than the other three groups (P=.007). CONCLUSION: This in vivo model
      using leak of the closure or the gastric yield pressure as endpoints for testing
      of the closure strength of a NOTES gastric access site seems to be reproducible.
      Our results support closure with T-tags and Padlock-G-clips over OVESCO OTS-clips
      and standard endoscopic clips.

PMID- 22145610
TI  - Population pharmacokinetics of ABT-594 in subjects with diabetic peripheral
      neuropathic pain.
AB  - WHAT IS KNOWN AND OBJECTIVE: ABT-594 is a non-opioid, non-NSAID analgesic. The
      objective of this work was to characterize the population pharmacokinetics of ABT
      594 in subjects with neuropathic pain. METHODS: Efficacy, safety and
      pharmacokinetics of ABT-594 in subjects with painful diabetic polyneuropathy were
      evaluated in a randomized, double-blind, placebo-controlled, parallel-group,
      multi-centre, 7-week Phase 2 study. Subjects (N=266) were approximately equally
      divided into four groups to receive BID regimens of placebo or 150, 225 and 300
      MUg of ABT-594. ABT-594 concentrations were determined from all subjects, whereas
      a subset of subjects provided intensive pharmacokinetic samples on two occasions.
      One- and two-compartment models were explored for characterizing plasma ABT-594
      concentration-time profiles. The relative importance of covariates (age, weight,
      body surface area, creatinine clearance, gender, nicotine use and albumin
      concentrations) was examined by use of the likelihood ratio test. Model building
      was accomplished using stepwise forward selection (P<0.05) and backward
      elimination (P<0.005) of covariates. Population analyses were performed using
      NONMEM. RESULTS AND DISCUSSION: Optimal characterization of the plasma
      concentration data was achieved using a one-compartment base model. Creatinine
      clearance and age were found to be significant covariates in the forward
      selection process; backward elimination process identified only creatinine
      clearance as a significant covariate. WHAT IS NEW AND CONCLUSION: A population
      pharmacokinetic model was developed to characterize ABT-594 concentrations in
      subjects with neuropathic pain. As ABT-594 is primarily eliminated as unchanged
      drug in the urine, creatinine clearance and age were significant covariates of
      clearance with creatinine clearance being the optimal predictor of ABT-594
      clearance.

PMID- 22145611
TI  - Symmetrization in a phosphinidene-bridged complex to give a diphosphanediyl
      derivative with metal-centered reactivity.
AB  - The phosphinidene complex [Mo(2)Cp(MU-kappa(1):kappa(1),eta(5)
      PC(5)H(4))(CO)(2)(eta(6)-HMes*)] reacts with CO to give the diphosphanediyl
      derivative [Mo(2){MU-kappa(1),eta(5):kappa(1),eta(5)
      (C(5)H(4))PP(C(5)H(4))}(eta(6)-HMes*)(2)]. The latter compound features
      unreactive lone electron pairs at phosphorus, which instead contribute to the
      electronic communication between metal centers via a weak pi(PP)-bonding
      interaction. As a result, this complex displays metal-centered acid-base and
      redox behavior.

PMID- 22145612
TI  - Nogo-66 inhibits adhesion and migration of microglia via GTPase Rho pathway in
      vitro.
AB  - Nogo-66 is a 66-amino-acid-residue extracellular domain of Nogo-A, which plays a
      key role in inhibition neurite outgrowth of central nervous system through
      binding to the Nogo-66 receptor (NgR) expressed on the neuron. Recent studies
      have confirmed that NgR is also expressed on the surface of macrophages/microglia
      in multiple sclerosis, but its biological effects remain unknown. In the present
      study, our results demonstrated that Nogo-66 triggered microglia anti-adhesion
      and inhibited their migration in vitro, which was mediated by NgR. We also
      assessed the roles of small GTP (glycosyl phosphatidylinositol)-binding proteins
      of the Rho family as the downstream signal transducers on the microglia adhesion
      and mobility induced by Nogo-66. The results showed that Nogo-66 activated RhoA
      and reduced the activity of Cdc42 in the meanwhile, which further triggered the
      anti-adhesion and migration inhibition effects to microglia. Nogo-66 inhibited
      microglia polarization and membrane protrusion formation, thus might eventually
      contribute to the decreasing capability of cell mobility. Taken together, the
      Nogo-66/NgR pathway may modulate neuroinflammation via mediating microglia
      adhesion and migration in addition to its role in neurons. Better understanding
      the relationship between Nogo-66/NgR and neuroinflammation may help targeting NgR
      for treating central nervous system diseases related with inflammation.

PMID- 22145613
TI  - A novel Gateway(r)-compatible binary vector allows direct selection of
      recombinant clones in Agrobacterium tumefaciens.
AB  - BACKGROUND: Cloning genes into plasmid vectors is one of the key steps for
      studying gene function. Recently, InvitrogenTM developed a convenient Gateway(r)
      cloning system based on the site-specific DNA recombination properties of
      bacteriophage lambda and the cytotoxic protein ccdB, which is lethal to most E.
      coli strains. The ccdB protein, however, is not toxic to Agrobacterium
      tumefaciens, an important player often used for studying gene function in planta.
      This limits the direct application of the Gateway(r) cloning system in plant
      transformation-mediated research. RESULTS: In this study, we constructed a novel
      Gateway(r)-compatible destination vector, pEG101-SacB/R, by replacing the ccdB
      gene with a SacB-SacR gene cassette as the negative selectable marker.
      CONCLUSION: Our results demonstrate that the new pEG101-SacB/R destination vector
      can be used for Gateway(r) cloning in Agrobacterium tumefaciens. pEG101-SacB/R
      will be a valuable tool for high-throughput functional analysis of genes in
      planta.

PMID- 22145614
TI  - Synthesis, antibacterial, antielastase, antiurease and antioxidant activities of
      new 1,4-butylene bridged bis-1,2,4-triazole derivatives.
AB  - A new bis schiffbases, 3 a-b were synthesized compound 2 with various bis
      aldehydes. Compounds 3 a-b have been reduced with NaBH(4) to afford the
      corresponding bis amino triazole compounds 4 a-b. The obtained products 3 a-b and
      4 a-b were identified by FTIR, (1)H-NMR, (13)C-NMR. A series of triazol
      derivatives were evaluated for their antibacterial, antioxidant, antiurease and
      antielastase activities. The results showed that the synthesized new bis-1,2,4
      triazole derivatives had effective antioxidant, antiurease and antielastase
      activities.

PMID- 22145615
TI  - Congenital penile drop: defective suspensory ligament versus severe proximal
      curvature, a case series.
AB  - INTRODUCTION: Penile drop is a condition where the erect penis is pointing
      downward. It can either be congenital or posttraumatic. Congenital cases can be
      attributed to either a defective penile suspensory ligament (PSL) or severe
      congenital curvature, with the point of maximum curvature proximal, at the base
      of the penis, concealed within the pubic fat (proximal penile curvature [PPC]).
      It is important to diagnose the underlying abnormality and choose the surgical
      approach accordingly, considering that surgical correction of PSL defects results
      in shortening that can be avoided in PPC cases. AIM: This work describes a method
      for discriminating PSL defects from PPC and their surgical management. MAIN
      OUTCOME MEASURES: Accuracy of preoperative diagnosis and results of surgery in
      terms of erection angle and penile length. METHODS: This is a retrospective study
      of the management of 12 male patients with congenital penile drop. Diagnostic
      measures were the pubic gap sign: palpation of a gap between the pubis and the
      penis, the straightening sign: patients with PSL defects can correct the angle of
      erection while contrary to PPC cases, Sexual Health Inventory for Men (SHIM), and
      intraoperative trial rotation of the corpora cavernosa that will correct PPC
      cases and point them out. Accordingly, PSL cases were managed by anchoring the
      base of the penis to the pubis, while PPC cases were managed by corporal
      rotation. RESULTS: Penile drop was fully corrected with shortening in PSL group
      and without in the PPC group. The straightening sign, SHIM, and trial rotation
      were in agreement contrary to the pubic gap sign. CONCLUSION: Discriminating PSL
      defects from PPC is possible by the combination between "straightening sign" and
      SHIM results. PSL cases should be managed by anchoring sutures despite the
      inevitable shortening. PPC cases can be spared the shortening by corporal
      rotation.

PMID- 22145619
TI  - A patient with spontaneous rupture of the esophagus and concomitant gastric
      cancer whose life was saved: case of report and review of the literature in
      Japan.
AB  - A 71-year-old man suddenly developed abdominal pain and vomiting on drinking soda
      after a meal, and visited a physician. Cervical subcutaneous and mediastinal
      emphysemas were observed on CT, and the patient was transferred to the emergency
      medical center of our hospital on the same day. Esophagography was performed at
      our department. A ruptured region was identified on the left side of the lower
      thoracic esophagus, and surgery was emergently performed employing sequential
      left thoracoabdominal incision. The chest wall was adhered due to inflammation,
      and large amounts of residual food and sloughing were present in the thoracic
      cavity and mediastinum. Moreover, necrotic changes were noted in the superior
      through inferior mediastinum. An about 2-cm rupture site was confirmed on the
      left side of the lower thoracic esophagus and closed by suture and filling with
      pediculate omentum. The presence of a tumorous lesion located mainly in the body
      of the stomach and lymph node enlargement were also diagnosed before surgery, for
      which gastric and intestinal fistulae were inserted to prepare for the second
      stage surgery. The patient was admitted to an ICU after surgery. ARDS and MRSA
      induced pneumonia and enteritis concomitantly developed but remitted. Curative
      surgery for gastric cancer was performed at 40 POD. Spontaneous rupture of the
      esophagus is relatively rare and that complicated by gastric caner is very rare,
      with only six cases being reported in Japan. Herein, we report the case.

PMID- 22145620
TI  - No evidence of inbreeding avoidance despite demonstrated survival costs in a
      polygynous rodent.
AB  - Individuals are generally predicted to avoid inbreeding because of detrimental
      fitness effects. However, several recent studies have shown that limited
      inbreeding is tolerated by some vertebrate species. Here, we examine the costs
      and benefits of inbreeding in a largely polygynous rodent, the yellow-bellied
      marmot (Marmota flaviventris). We use a pedigree constructed from 8 years of
      genetic data to determine the relatedness of all marmots in our study population
      and examine offspring survival, annual male reproductive success, relatedness
      between breeding pairs and the effects of group composition on likelihood of male
      reproduction to assess inbreeding in this species. We found decreased survival in
      inbred offspring, but equal net reproductive success among males that inbred and
      those that avoided it. Relatedness between breeding pairs was greater than that
      expected by chance, indicating that marmots do not appear to avoid breeding with
      relatives. Further, male marmots do not avoid inbreeding: males mate with equal
      frequency in groups composed of both related and unrelated females and in groups
      composed of only female relatives. Our results demonstrate that inbreeding can be
      tolerated in a polygynous species if the reproductive costs of inbreeding are low
      and individuals that mate indiscriminately do not suffer decreased reproductive
      success.

PMID- 22145621
TI  - Enantioselective bromocycloetherification by Lewis base/chiral Bronsted acid
      cooperative catalysis.
AB  - A binary catalyst system for the enantioselective bromocycloetherification of 5
      arylpentenols is described. The combination of an achiral Lewis base and a chiral
      Bronsted acid affords good enantioselectivities for the cyclization of Z
      configured 5-arylpentenols to form bromomethyltetrahydrofurans. The
      constitutional site selectivity is highly dependent upon the aromatic substituent
      and the configuration of the double bond.

PMID- 22145622
TI  - The effect of radiofrequency radiation on DNA and lipid damage in female and male
      infant rabbits.
AB  - PURPOSE: We aimed to design a prolonged radiofrequency (RF) radiation exposure
      and investigate in an animal model, possible bio-effects of RF radiation on the
      ongoing developmental stages of children from conception to childhood. MATERIALS
      AND METHODS: A total of 72 New Zealand female and male white rabbits aged one
      month were used. Females were exposed to RF radiation for 15 min/day during 7
      days, whereas males were exposed to the same level of radiation for 15 min/day
      during 14 days. Thirty-six female and 36 male infant rabbits were randomly
      divided into four groups: Group I [Intrauterine (IU) exposure (-); Extrauterine
      (EU) exposure (-)]: Sham exposure which means rabbits were exposed to 1800 MHz
      Global System for Mobile Telecommunication (GSM)-like RF signals neither in the
      IU nor in the EU periods. Group II [IU exposure (-); EU exposure (+)]: Infant
      rabbits were exposed to 1800 MHz GSM-like RF signals when they reached one month
      of age. Group III [IU exposure (+); EU exposure (-)]: Infant rabbits were exposed
      to 1800 MHz GSM-like RF signals in the IU period (between 15th and 22nd days of
      the gestational period). Group IV [IU exposure (+); EU exposure (+)]: Infant
      rabbits were exposed to 1800 MHz GSM-like RF signals both in the IU period
      (between 15th and 22nd days of the gestational period) and in the EU period when
      they reached one month of age. Biochemical analysis for lipid peroxidation and
      DNA damage were carried out in the livers of all rabbits. RESULTS: Lipid
      peroxidation levels in the liver tissues of female and male infant rabbits
      increased under RF radiation exposure. Liver 8-hydroxy-2'-deoxyguanosine (8-OHdG)
      levels of female rabbits exposed to RF radiation were also found to increase when
      compared with the levels of non-exposed infants. However, there were no changes
      in liver 8-OHdG levels of male rabbits under RF exposure. CONCLUSION:
      Consequently, it can be concluded that GSM-like RF radiation may induce
      biochemical changes by increasing free radical attacks to structural biomolecules
      in the rabbit as an experimental animal model.

PMID- 22145623
TI  - Differentially expressed profiles in the larval testes of Wolbachia infected and
      uninfected Drosophila.
AB  - BACKGROUND: Wolbachia are endosymbiotic bacteria that are frequently found in
      arthropods and nematodes. These maternally inherited bacteria manipulate host
      reproduction by several mechanisms including cytoplasmic incompatibility (CI). CI
      is the most common phenotype induced by Wolbachia and results in the
      developmental arrest of embryos derived from crosses between Wolbachia-infected
      males and uninfected females. Although the molecular mechanisms of CI are
      currently unknown, several studies suggest that host sperm is modified by
      Wolbachia during spermatogenesis. RESULTS: We compared the gene expression of
      Drosophila melanogaster larval testes with and without the wMel strain of
      Wolbachia to identify candidate genes that could be involved in the interaction
      between Wolbachia and the insect host. Microarray, quantitative RT-PCR and in
      situ hybridization analyses were carried out on D. melanogaster larval testes to
      determine the effect of Wolbachia infection on host gene expression. A total of
      296 genes were identified by microarray analysis to have at least a 1.5 fold
      change [q-value < 5%] in expression. When comparing Wolbachia-infected flies to
      uninfected flies, 167 genes were up-regulated and 129 genes down-regulated.
      Differential expression of genes related to metabolism, immunity, reproduction
      and other functions were observed. Quantitative RT-PCR (qRT-PCR) confirmed 12
      genes are differentially expressed in the testes of the 3rd instar larvae of
      Wolbachia-infected and uninfected flies. In situ hybridization demonstrated that
      Wolbachia infection changes the expression of several genes putatively associated
      with spermatogenesis including JH induced protein-26 and Mst84Db, or involved in
      immune (kenny) or metabolism (CG4988-RA). CONCLUSIONS: Wolbachia change the gene
      expression of 296 genes in the larval testes of D. melanogaster including genes
      related to metabolism, immunity and reproduction. Interestingly, most of the
      genes putatively involved in immunity were up-regulated in the presence of
      Wolbachia. In contrast, most of the genes putatively associated with reproduction
      (especially spermatogenesis) were down-regulated in the presence of Wolbachia.
      These results suggest Wolbachia may activate the immune pathway but inhibit
      spermatogenesis. Our data provide a significant panel of candidate genes that may
      be involved in the interaction between Wolbachia and their insect hosts. This
      forms a basis to help elucidate the underlying mechanisms of Wolbachia-induced CI
      in Drosophila and the influence of Wolbachia on spermatogenesis.

PMID- 22145624
TI  - Structure, mechanism, and evolution of Ero1 family enzymes.
AB  - SIGNIFICANCE: Disulfide bond formation is an essential reaction involved in the
      folding and maturation of many secreted and membrane proteins. Both prokaryotic
      and eukaryotic cells utilize various disulfide oxidoreductases and redox-active
      cofactors to accelerate this oxidative reaction, and higher eukaryotes have
      diversified and refined these disulfide-introducing cascades over the course of
      evolution. RECENT ADVANCES: In the past decade, atomic resolution structures have
      been solved for an increasing number of disulfide oxidoreductases, thereby
      revealing the structural and mechanistic basis of cellular disulfide bond
      formation systems. CRITICAL ISSUES: In this review, we focus on the evolution,
      structure, and regulatory mechanisms of endoplasmic reticulum oxidoreductin 1
      (Ero1) family enzymes, the primary disulfide bond-generating catalysts in the
      endoplasmic reticulum (ER). Detailed comparison of Ero1 with other
      oxidoreductases, such as Prx4, QSOX, Erv1/2, and disulfide bond protein B (DsbB),
      provides important insight into how this ER-resident flavoenzyme acts in a
      regulated and specific manner to maintain redox and protein homeostasis in
      eukaryotic cells. FUTURE DIRECTIONS: Currently, it is presumed that multiple
      pathways in addition to that mediated by Ero1 cooperate to achieve oxidative
      folding of many secretory and membrane proteins in mammalian cells. The important
      open question is how each oxidative pathway works distinctly or redundantly in
      response to various cellular conditions.

PMID- 22145625
TI  - The GPCR OGR1 (GPR68) mediates diverse signalling and contraction of airway
      smooth muscle in response to small reductions in extracellular pH.
AB  - BACKGROUND AND PURPOSE: Previous studies have linked a reduction in pH in airway,
      caused by either environmental factors, microaspiration of gastric acid or
      inflammation, with airway smooth muscle (ASM) contraction and increased airway
      resistance. Neural mechanisms have been shown to mediate airway contraction in
      response to reductions in airway pH to < 6.5; whether reduced extracellular pH
      (pHo) has direct effects on ASM is unknown. EXPERIMENTAL APPROACH: Intracellular
      signalling events stimulated by reduced pHo in human cultured ASM cells were
      examined by immunoblotting, phosphoinositide hydrolysis and calcium mobilization
      assays. ASM cell contractile state was examined using magnetic twisting
      cytometry. The expression of putative proton-sensing GPCRs in ASM was assessed by
      real-time PCR. The role of ovarian cancer G protein-coupled receptor 1 (OGR1 or
      GPR68) in acid-induced ASM signalling and contraction was assessed in cultures
      subjected to siRNA-mediated OGR1 knockdown. KEY RESULTS: ASM cells responded to
      incremental reductions in pHo (from pH 8.0 to pH 6.8) by activating multiple
      signalling pathways, involving p42/p44, PKB, PKA and calcium mobilization.
      Coincidently, ASM cells contracted in response to decreased pHo with similar
      'dose'-dependence. Real-time PCR suggested OGR1 was the only proton-sensing GPCR
      expressed in ASM cells. Both acid-induced signalling (with the exception of PKB
      activation) and contraction were significantly attenuated by knockdown of OGR1.
      CONCLUSIONS AND IMPLICATIONS: These studies reveal OGR1 to be a physiologically
      relevant GPCR in ASM cells, capable of pleiotropic signalling and mediating
      contraction in response to small reductions in extracellular pH. Accordingly, ASM
      OGR1 may contribute to asthma pathology and represent a therapeutic target in
      obstructive lung diseases.

PMID- 22145626
TI  - ATP-binding cassette member A3 (E292V) gene mutation and pulmonary morbidity in
      very-low-birth-weight infants.
AB  - AIM: ATP-binding cassette member A 3 (ABCA3) plays a critical role for the
      transport of surfactant phospholipids into the lamellar bodies of type II
      alveolar epithelial cells. Term infants carrying the E292V missense mutation of
      the gene encoding ABCA3 are likely to develop respiratory distress syndrome, and
      the mutation has also been linked to interstitial lung disease in paediatric
      patients. The aim of this study was to investigate the association of the E292V
      genotype with pulmonary morbidity in a large cohort of very-low-birth-weight
      (VLBW) infants. METHODS: We performed a genetic association study with a
      prospective, population-based multi-centre cohort of 3177 VLBW infants born in 16
      German study centres between 2003 and 2009 (German Neonatal Network). The ABCA3
      genotype was determined by restriction fragment length polymorphism-PCR in
      genomic DNA samples derived from buccal swabs. RESULTS: In a large cohort of 3177
      VLBW infants, 11 individuals were found to be heterozygote for the E292V mutation
      (0.34%). After stratification according to ABCA3 genotype, no differences were
      noted for clinical characteristics, necessary treatments and neonatal pulmonary
      outcomes. CONCLUSIONS: Within the size limits of our study cohort, the ABCA3
      missense mutation E292V had no remarkable effect on pulmonary outcome in VLBW
      infants. Present results do not rule out the possibility that E292V phenotype is
      associated with minor difference in the morbidity.

PMID- 22145628
TI  - Microbial status and product labelling of 58 original tattoo inks.
AB  - BACKGROUND: European Council resolutions on tattoo ink introduce sterility and
      preservation of inks to protect customers. Inks used in Denmark are typically
      purchased over the internet from international suppliers and manufacturers from
      the US and the UK. In Denmark tattoo inks are regulated and labelled according to
      REACH as if they were plain chemicals. OBJECTIVE: The objective of this study was
      to check the microbial product safety of unopened and opened tattoo ink stock
      bottles. Packaging, labelling, preservation, sterility and contamination with
      micro-organisms were studied. METHODS: Physical inspection and culture of
      bacteria and fungi. RESULTS: Six of 58 unopened stock bottles (10%) were
      contaminated with bacteria and one of six samples (17%) of previously used stock
      bottles was contaminated. The bacterial species represented bacteria considered
      pathogenic in humans as well as non-pathogenic environmental bacteria. Yeast or
      moulds were detected in none of the samples. A total of 31% of the manufacturers
      informed only about the brand name. No information about content, sterility,
      risks or expiry date was indicated on the label. A total of 42% claimed sterility
      of their inks. A total of 54% labelled a maximum period of durability of
      typically 2-3 years. The physical sealing was leaking in 28% of the products.
      CONCLUSIONS: The European Council resolutions regarding safety of tattoo inks are
      not effective. Stock bottles of tattoo ink may contain bacteria pathogenic to
      humans and environmental bacteria, and packaging, labelling and preservation of
      inks are of inadequate quality. Claim of sterility can be erroneous.

PMID- 22145627
TI  - Silica coated paper substrate for paper-spray analysis of therapeutic drugs in
      dried blood spots.
AB  - Paper spray is a newly developed ambient ionization method that has been applied
      for direct qualitative and quantitative analysis of biological samples. The
      properties of the paper substrate and spray solution have a significant impact on
      the release of chemical compounds from complex sample matrices, the diffusion of
      the analytes through the substrate, and the formation of ions for mass
      spectrometry analysis. In this study, a commercially available silica-coated
      paper was explored in an attempt to improve the analysis of therapeutic drugs in
      dried blood spots (DBS). The dichloromethane/isopropanol solvent has been
      identified as an optimal spray solvent for the analysis. The comparison was made
      with paper spray using chromatography paper as substrate with methanol/water as
      solvent for the analysis of verapamil, citalopram, amitriptyline, lidocaine, and
      sunitinib in dried blood spots. It has been demonstrated that the efficiency of
      recovery of the analytes was notably improved with the silica coated paper and
      the limit of quantitation (LOQ) for the drug analysis was 0.1 ng mL(-1) using a
      commercial triple quadrupole mass spectrometer. The use of silica paper substrate
      also resulted in a sensitivity improvement of 5-50-fold in comparison with
      chromatography papers, including the Whatman ET31 paper used for blood cards.
      Analysis using a hand-held miniature mass spectrometer Mini 11 gave LOQs of 10-20
      ng mL(-1) for the tested drugs, which is sufficient to cover the therapeutic
      ranges of these drugs.

PMID- 22145629
TI  - Synthesis, biological evaluation, and docking studies of tetrahydrofuran-
      cyclopentanone- and cyclopentanol-based ligands acting at adrenergic alpha1- and
      serotonine 5-HT1A receptors.
AB  - A series of aralkylphenoxyethylamine and aralkylmethoxyphenylpiperazine compounds
      was synthesized and their in vitro pharmacological profile at both 5-HT(1A)
      receptors and alpha(1)-adrenoceptor subtypes was measured by binding assay and
      functional studies. The results showed that the replacement of the 1,3-dioxolane
      ring by a tetrahydrofuran, cyclopentanone, or cyclopentanol moiety leads to an
      overall reduction of in vitro affinity at the alpha(1)-adrenoceptor while both
      potency and efficacy were increased at the 5-HT(1A) receptor. A significant
      improvement of 5-HT(1A)/alpha(1) selectivity was observed in some of the
      cyclopentanol derivatives synthesized (4acis, 4ccis and trans). Compounds 2a and
      4ccis emerged as novel and interesting 5-HT(1A) receptor antagonist (pK(i) =
      8.70) and a 5-HT(1A) receptor partial agonist (pK(i) = 9.25, pD(2) = 9.03, E(max)
      = 47%, 5-HT(1A)/alpha(1a) = 69), respectively. Docking studies were performed at
      support of the biological data and to elucidate the molecular basis for 5-HT(1A)
      agonism/antagonism activity.

PMID- 22145631
TI  - Depressive symptoms and intimate partner violence in the 12 months after
      childbirth: a prospective pregnancy cohort study.
AB  - OBJECTIVE: To examine maternal depressive symptoms during and after pregnancy and
      explore their relationship with intimate partner violence in the 12 months after
      birth. DESIGN: Prospective pregnancy cohort study of nulliparous women. SETTING:
      Melbourne, Australia. POPULATION: In all, 1507 eligible women completed baseline
      data (mean gestation 15 weeks). Analyses are presented for 1305 women who
      completed all follow-up questionnaires. METHODS: Women were recruited from six
      public hospitals at between 6 and 24 weeks of gestation. Written questionnaires
      were completed at recruitment and at 3, 6 and 12 months postpartum. MAIN OUTCOME
      MEASURES: Depressive symptoms were assessed using the Edinburgh Postnatal
      Depression Scale (EPDS). Intimate partner violence was assessed using the short
      version of the Composite Abuse Scale. RESULTS: Sixteen per cent of women reported
      depressive symptoms (EPDS >= 13) in the 12 months postpartum, with most women
      first reporting depressive symptoms in the second 6 months after birth. Around
      40% of women reporting depressive symptoms at each follow up also reported
      intimate partner violence. Factors associated with postpartum depressive symptoms
      in multivariable models were: emotional abuse alone (adjusted odds ratio [OR]
      2.72, 95% CI 1.72-4.13), physical abuse (adjusted OR 3.94, 95% CI 2.44-6.36),
      depression in pregnancy (adjusted OR 2.89, 95% CI 1.75-4.77) and unemployment in
      early pregnancy (adjusted OR 1.60, 95% CI 1.03-2.48). CONCLUSIONS: Screening for
      maternal depression at 3 months postpartum or earlier may miss over half the
      women with depression in the first 12 months after birth. Intimate partner
      violence is common among women reporting postnatal depressive symptoms and may be
      an important factor for health professionals to consider in their management.

PMID- 22145632
TI  - Effectiveness of nasopharyngoscopic biofeedback in clients with cleft palate
      speech: a systematic review.
AB  - OBJECTIVE: To conduct a systematic review analyzing the effectiveness of
      nasopharyngoscopic biofeedback in clients with cleft lip and palate and
      velopharyngeal dysfunction. METHOD: Extensive electronic search and analysis of
      the databases of Cochrane Library, MEDLINE, EMBASE, ERIC, PsycInfo, CINAHL, AMED,
      Journals@Ovid, and German Databases, including all papers published since 1970
      plus a manual search of the Cleft Palate-Craniofacial Journal (1970-3/2010).
      RESULTS: Six studies met the inclusion criteria. Their analysis reflects a low
      level of evidence and a broad heterogeneity concerning age range, intervention
      methods, and outcome measurement. CONCLUSION: The analyzed studies show that
      nasopharyngoscopy may be effective only in combination with traditional speech
      therapy in helping patients with cleft palate speech optimize their
      velopharyngeal closure in articulation, but the quantity and quality of studies
      are limited.

PMID- 22145633
TI  - Effects of smoking on plasma testosterone level and erectile function in rats.
AB  - INTRODUCTION: There have been several conflicting reports of the effects of
      smoking on plasma testosterone levels and erectile function in clinical and
      animal studies. AIM: This study was conducted to determine the actual effects of
      smoking on plasma testosterone levels and erectile function in rat-smoking
      models. METHODS: For the exposure to cigarette smoke, the rats in a cage had a
      constant influx of smoke using a specially constructed device. Twenty-four
      Sprague Dawley (SD) rats for the acute cigarette exposure were allocated randomly
      into two groups: an experimental group and a control group. Thirty-six SD rats
      for the chronic cigarette smoke exposure were randomly divided into three groups:
      a control group and two experimental groups. MAIN OUTCOME MEASURES: After
      exposure to smoking, the rats were subjected to electrical field stimulation of
      the cavernosal nerve to assess the erectile function, and blood was collected to
      measure the levels of plasma thiocyanate, testosterone, luteinizing hormone, and
      follicle-stimulating hormone. The histological changes of testes and corpora
      cavernosum (CC) were examined. RESULTS: In the smoking groups, the thiocyanate
      levels were significantly higher than in the control group. Also, the mean
      arterial pressure (MAP) was significantly higher in the smoking groups, but the
      corpora cavernosal filling rate and maximal intracavernosal pressure/MAP were
      significantly lower than in the control group. The testosterone levels of
      experimental groups were significantly lower than those of control group, and the
      testosterone and thiocyanate levels were significantly correlated with erectile
      function components in chronic smoking groups. There was no significant
      histological change in the testes; however, in the CC, there was an increase in
      collagen fibers and decrease in smooth muscle and sinusoidal space in chronic
      smoking groups. CONCLUSION: The results suggest that both the vasoconstrictor
      effects of smoking and the decrease in testosterone levels after chronic smoking
      had some effects on erectile function in rats.

PMID- 22145634
TI  - Extended release of bevacizumab by thermosensitive biodegradable and
      biocompatible hydrogel.
AB  - The antibody bevacizumab (Avastin) has been used clinically to treat intraocular
      neovascular diseases based on its antivascular endothelial growth factor (VEGF)
      character. The anti-VEGF strategy for retinal neovascular diseases is limited by
      the short half-life of bevacizumab and thus requires frequent injections. This
      Article reports the sustained release of bevacizumab from a biocompatible
      material that is composed of a triblock copolymer of poly(2-ethyl-2-oxazoline)-b
      poly(epsilon-caprolactone)-b-poly(2-ethyl-2-oxazoline) (PEOz-PCL-PEOz). The
      amphiphilic PEOz-PCL-PEOz triblock copolymer was synthesized in three steps.
      First, the PEOz was polymerized by methyl p-toluenesulfonate and 2-ethyl-2
      oxazoline (EOz), and the living end was terminated by potassium hydroxide
      methanolic solution. Subsequently, the hydroxyl-PEOz was used as a macroinitiator
      for the ring-opening polymerization of epsilon-caprolactone using a Tin(II)
      octoate catalyst to synthesize the telechelic hydroxylated PEOz-PCL. Finally, the
      PEOz-PCL-PEOz triblock copolymer was obtained using the 1,6-hexamethylene
      diisocyanateas a coupling reagent. The PEOz-PCL-PEOz was chemically and
      molecularly characterized by GPC, (1)H NMR, and FTIR, and its aqueous solution
      (ECE hydrogel) showed a reversible sol (room temperature)-gel (physiological
      temperature) phase transition, which serves as an easy antibody-packing system
      with extended release. The biodegradability of ECE hydrogel was assessed by the
      porosity formation at different periods by scanning electron microscopy. The ECE
      hydrogel had no in vitro cytotoxicity on the human retinal pigment epithelial
      cell line by flow cytometry. The histomorphology and electrophysiology of the
      rabbit neuroretina were preserved after 2 months of intravitreal injection. In
      conclusion, the ECE hydrogel has a temperature-sensitive sol-gel phase transition
      and is effective in vitro. Its intraocular biocompatibility demonstrated its
      great potential to be widely used in biomedical applications for extended drug
      release.

PMID- 22145635
TI  - Recombinase technology for gene therapy.

PMID- 22145636
TI  - In vitro photodynamic inactivation of Cryptococcus neoformans melanized cells
      with chloroaluminum phthalocyanine nanoemulsion.
AB  - The selection of fungi resistant to currently used fungicides and the emergence
      of new pathogenic species make the development of alternative fungus-control
      techniques highly desirable. Photodynamic antimicrobial chemotherapy (PACT) is a
      promising method which combines a nontoxic photosensitizer (PS) with visible
      light to cause selective killing of microbial cells. The development of PACT to
      treat mycoses or kill fungi in the environment depends on identifying effective
      PS for the different pathogenic species and delivery systems able to expand and
      optimize their use. In the present study, the in vitro susceptibility of
      Cryptococcus neoformans melanized cells to the photodynamic effects of the PS
      agent ClAlPc in nanoemulsion (ClAlPc/NE) was examined. Cells were killed in a PS
      concentration- and light dose-dependent manner. Treatment with ClAlPc/NE, using
      PS concentrations (e.g. 4.5 MUm) and light doses (e.g. 10 J cm(-2)) compatible
      with PACT, resulted in a reduction of up to 6 logs in survival. Washing the cells
      to remove unbound PS before light exposure did not inhibit fungal photodynamic
      inactivation. Internalization of ClAlPc by C. neoformans was confirmed by
      confocal fluorescence microscopy, and the degree of uptake was dependent on PS
      concentration.

PMID- 22145637
TI  - Getting BETTER: breaking the ice and warming to the inclusion of sexuality in
      mental health nursing care.
AB  - Discussing sexual issues with consumers is considered a nursing role, yet it is
      commonly avoided. Research suggests that sexual issues and difficulties are
      particularly evident in mental health settings, and failure to address these
      issues represents a significant gap in care and treatment. Specific models for
      raising sexual issues have been used in oncology and cardiac care settings to
      assist clinicians. A descriptive, exploratory study was conducted with mental
      health nurses from Queensland, Australia. The aim of this research was to explore
      whether a specific model, the BETTER model (bring up, explain, tell, time,
      educate, record) was useful in assisting mental health nurses in raising the
      topic of sexuality with consumers. In-depth interviews explored participants'
      attitudes and experiences of discussing sexuality. Participants were introduced
      to the BETTER model, and were asked to trial the approach with consumers. They
      were then interviewed a second time. Two main themes emerged: greater awareness
      and becoming part of practice. Participants described a transformation of their
      practice from one of avoiding issues of sexuality with consumers, to a position
      of inclusion, which became embedded within practice. Participants did not tend to
      use the model in a structured way, and it appears that knowledge and awareness
      were more useful than the model itself.

PMID- 22145638
TI  - Syntheses, characterization, and magnetic studies of copper(II) complexes with
      the ligand N,N,N',N'-tetrakis(2-pyridylmethyl)-1,3-benzenediamine (1,3-tpbd) and
      its phenol derivative 2,6-bis[bis(2-pyridylmethyl)amino]-p-cresol] (2,6-Htpcd).
AB  - The copper(II) complexes [Cu(4)(1,3
      tpbd)(2)(H(2)O)(4)(NO(3))(4)](n)(NO(3))(4n).13nH(2)O (1), [Cu(4)(1,3
      tpbd)(2)(AsO(4))(ClO(4))(3)(H(2)O)](ClO(4))(2).2H(2)O.0.5CH(3)OH (2), [Cu(4)(1,3
      tpbd)(2)(PO(4))(ClO(4))(3)(H(2)O)](ClO(4))(2).2H(2)O.0.5CH(3)OH (3), [Cu(2)(1,3
      tpbd){(PhO)(2)PO(2)}(2)](2)(ClO(4))(4) (4), and [Cu(2)(1,3
      tpbd){(PhO)PO(3)}(2)(H(2)O)(0.69)(CH(3)CN)(0.31)](2)(BPh(4))(4).Et(2)O.CH(3)CN
      (5) [1,3-tpbd = N,N,N',N'-tetrakis(2-pyridylmethyl)-1,3-benzenediamine, BPh(4)(-)
      = tetraphenylborate] were prepared and structurally characterized. Analyses of
      the magnetic data of 2, 3, 4, and [Cu(2)(2,6-tpcd)(H(2)O)Cl](ClO(4))(2) (6) [2,6
      tpcd = 2,6-bis[bis(2-pyridylmethyl)amino]-p-cresolate] show the occurrence of
      weak antiferromagnetic interactions between the copper(II) ions, the bis
      terdentate 1,3-tpbd/2,6-tpcd, MU(4)-XO(4) (X = As and P) MU(1,2)-OPO and MU
      O(phenolate) appearing as poor mediators of exchange interactions in this series
      of compounds. Simple orbital symmetry considerations based on the structural
      knowledge account for the small magnitude of the magnetic couplings found in
      these copper(II) compounds.

PMID- 22145639
TI  - Immunomodulatory properties of S- and N-alkylated 5-(1H-indol-2-yl)-1,3,4
      oxadiazole-2(3H)-thione.
AB  - A series of S- and N-alkylated indolyloxadiazoles 2-7 were prepared. All
      compounds were tested for their immunomodulatory activity against T-cell
      proliferation, oxidative burst and cytokine analysis. Compounds 1, 2a, 2b, 2c and
      2k demonstrated highly significant (P <= 0.005) inhibition on PHA activated T
      cell proliferation with IC(50) less than 3 ug/mL concentration, while 3b exert a
      moderate inhibitory effect with IC(50) 8.6 ug/mL. Among all compounds of the
      series, only 2h was found to suppress phagocytes ROS production (IC(50) 2.4
      ug/mL) in luminol-based chemiluminescence (CL) assay. Compounds 2a-k have
      stimulatory effect on proinflammatory cytokine predominantly IL-1beta but no
      effect on IL-4 and NO production indicating that these compounds might have
      selective inhibitory effect on T-cell proliferation. Cytotoxic effect on T-cell
      proliferation was tested on NIH-3T3 mouse fibroblast normal cell line. All
      compounds were found to be free from toxic effects up to 100 MUM concentration.

PMID- 22145640
TI  - Theoretical study of the reactions of 2-chlorophenol over the dehydrated and
      hydroxylated silica clusters.
AB  - Silica is the main component of combustion-generated fly ash and is expected to
      have an important impact on the formation of polychlorinated dibenzo-p-dioxins
      (PCDDs) and polychlorinated dibenzofurans (PCDFs) in municipal waste
      incinerators. In this work, we theoretically studied the reactions of 2
      chlorinated phenol (2-CP) over the clusters (SiO(2))(3) and (SiO(2))(3)O(2)H(4),
      which mimic the dehydrated and hydroxylated silica structures, respectively. The
      dehydrated cluster is much more active toward the attack of 2-CP to form highly
      stable 2-chlorophenolate than the hydroxylated silica cluster. The further
      dissociation of chlorophenolates to form CP radicals (CPRs) is calculated to be
      very difficult. The calculated energy barrier of the reaction of 2-CP over the
      dehydrated (SiO(2))(3) cluster and IR data are in good agreement with early
      experimental observations. On the basis of the calculated results, we propose
      that the formation of PCDD/Fs from CPs over silica surfaces may not involve CPRs,
      but be relevant to the further conversion of chlorophenolates over silica
      surfaces. This mechanism is very different from the corresponding reactions
      mediated by transition metal oxides. The results presented here may be helpful to
      understand the chemisorption mechanism of CPs on silica surfaces in real waste
      combustion.

PMID- 22145641
TI  - First experience with a new negative pressure incision management system on
      surgical incisions after cardiac surgery in high risk patients.
AB  - BACKGROUND: Sternal wound infection remains a serious potential complication
      after cardiac surgery. A recent development for preventing wound complications
      after surgery is the adjunctive treatment of closed incisions with negative
      pressure wound therapy. Suggested mechanisms of preventive action are improving
      the local blood flow, removing fluids and components in these fluids, helping
      keep the incision edges together, protecting the wound from external
      contamination and promoting incision healing. This work reports on our initial
      evaluation and clinical experience with the PrevenaTMIncision Management System,
      a recently introduced new negative pressure wound therapy system specifically
      developed for treating closed surgical incisions and helping prevent potential
      complications. We evaluated the new treatment on sternal surgical incisions in
      patients with multiple co-morbidities and consequently a high risk for wound
      complications. METHODS: The PrevenaTMincision management system was used in 10
      patients with a mean Fowler risk score of 15.1 [Range 8-30]. The negative
      pressure dressing was applied immediately after surgery and left in place for 5
      days with a continuous application of -125 mmHg negative pressure. Wounds and
      surrounding skin were inspected immediately after removal of the PrevenaTM
      incision management system and at day 30 after surgery. RESULTS: Wounds and
      surrounding skin showed complete wound healing with the absence of skin lesions
      due to the negative pressure after removal of the PrevenaTM dressing. No device
      related complications were observed. No wound complications occurred in this high
      risk group of patients until at least 30 days after surgery. CONCLUSIONS: The
      PrevenaTMsystem appears to be safe, easy to use and may help achieve
      uncomplicated wound healing in patients at risk of developing wound complications
      after cardiothoracic surgery.

PMID- 22145642
TI  - Self-management skills in adolescents with chronic rheumatic disease: A cross
      sectional survey.
AB  - BACKGROUND: For adolescents with a diagnosis of lifelong chronic illness, mastery
      of self-management skills is a critical component of the transition to adult
      care. This study aims to examine self-reported medication adherence and self-care
      skills among adolescents with chronic rheumatic disease. METHODS: Cross-sectional
      survey of 52 adolescent patients in the Pediatric Rheumatology Clinic at UCSF.
      Outcome measures were self-reported medication adherence, medication regimen
      knowledge and independence in health care tasks. Predictors of self-management
      included age, disease perception, self-care agency, demographics and self
      reported health status. Bivariate associations were assessed using the Student's
      t-test, Wilcoxon rank sum test and Fisher exact test as appropriate. Independence
      in self-management tasks were compared between subjects age 13-16 and 17-20 using
      the chi-squared test. RESULTS: Subjects were age 13-20 years (mean 15.9); 79%
      were female. Diagnoses included juvenile idiopathic arthritis (44%), lupus (35%),
      and other rheumatic conditions (21%). Mean disease duration was 5.3 years (SD
      4.0). Fifty four percent reported perfect adherence to medications, 40% reported
      1-2 missed doses per week, and 6% reported missing 3 or more doses. The most
      common reason for missing medications was forgetfulness. Among health care tasks,
      there was an age-related increase in ability to fill prescriptions, schedule
      appointments, arrange transportation, ask questions of doctors, manage insurance,
      and recognize symptoms of illness. Ability to take medications as directed, keep
      a calendar of appointments, and maintain a personal medical file did not improve
      with age. CONCLUSIONS: This study suggests that adolescents with chronic
      rheumatic disease may need additional support to achieve independence in self
      management.

PMID- 22145646
TI  - Resveratrol modifies tephritid fruit fly response to radiation but not
      nutritional stress.
AB  - PURPOSE: Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenol compound found
      in many plants and fruits that has antioxidant and radioprotective properties.
      Two model invertebrates, Bactrocera dorsalis (oriental fruit fly) and B.
      cucurbitae (melon fly) (Diptera: Tephritidae), were studied to determine if the
      addition of resveratrol to an artificial diet could modify their response to
      radiation and nutritional stress. MATERIALS AND METHODS: Resveratrol at
      concentrations of 0, 50, 100, or 200 MUM of was incorporated into a liquid larval
      fruit fly diet. Third instars were treated with: (i) A radiation dose of 30 Gy
      (radiation stress), (ii) a wheat germ oil-deficient diet (nutritional stress), or
      (iii) left untreated as a control. RESULTS: The addition of resveratrol to the
      diet partially mitigated the adverse effects of radiation on several life history
      parameters. In B. cucurbitae, a significantly higher 49-53% of adults could fly
      when 50-200 MUM resveratrol was added to the diet compared with 32% in irradiated
      flies reared without resveratrol. B. cucurbitae egg hatch in irradiated insects
      improved significantly from 46 to 66% with the addition of 50 MUM resveratrol. In
      irradiated B. dorsalis, adult emergence was significantly improved from 12 to 29%
      with the addition of 100 MUM resveratrol. Resveratrol did not mediate any of the
      negative effects of a wheat germ oil-deficient diet in either species.
      CONCLUSION: Resveratrol has potential as a means to partially mitigate the
      adverse effects of radiation treatment under the conditions tested. This study is
      the first to show that resveratrol can have radioprotective effects in
      invertebrates.

PMID- 22145647
TI  - Total synthesis of penostatin B.
AB  - The first total synthesis of penostatin B has been accomplished by using a highly
      diastereoselective Pauson-Khand reaction and an efficient relay ring-closing
      metathesis for the construction of the basic carbon skeleton of the natural
      product as the key steps.

PMID- 22145648
TI  - Relation of bronchial and alveolar nitric oxide to exercise-induced
      bronchoconstriction in atopic children and adolescents.
AB  - BACKGROUND AND OBJECTIVE: Exercise challenge test is widely used in diagnostics
      and follow-up of childhood asthma, but the method is complex, time consuming, and
      expensive. In this study, we aimed to find out whether flow-independent nitric
      oxide (NO) parameters (bronchial NO flux [J'aw(NO)] and alveolar NO concentration
      [CA(NO)]) predict exercise-induced bronchoconstriction (EIB) in atopic children
      and adolescents with asthma-like symptoms. Also, the respective NO parameters
      corrected for axial backward diffusion (J'aw(NO) [TMAD] and CA(NO) [TMAD]) were
      calculated and included in the analysis. METHODS: Thirty patients (6-19 yr old)
      with confirmed atopy (positive skin prick tests or allergen-specific IgE) and
      asthma-like respiratory symptoms were included in the study. Before the current
      investigations, none of the patients had been diagnosed to have asthma and none
      were on inhaled corticosteroids. Exhaled NO was measured at multiple exhalation
      flow rates, and exercise challenge test was carried out. Bronchial NO flux and
      alveolar NO concentration were calculated according to the linear method with and
      without correction for axial backward diffusion. Sixty-six healthy school
      children served as controls. RESULTS: The patients were divided into two groups
      according to EIB. Patients with EIB (EIB+ group, n = 18) had enhanced bronchial
      NO output as compared to patients without EIB (EIB- group, n = 12); but the EIB-
      group did not differ from healthy controls. EIB+ group had also higher alveolar
      NO concentration than EIB- group and healthy controls, but EIB- group did not
      differ from healthy controls. When bronchial NO flux and alveolar NO
      concentration were corrected for axial diffusion, J'aw(NO) (TMAD) had equal
      difference as J'aw(NO) between the groups as expected. However, only EIB+ had
      higher CA(NO) (TMAD) than healthy controls, and the patient groups did not differ
      from each other. In patients, bronchial NO output correlated with the magnitude
      of exercise-induced change in PEF (r(s) = -0.388, p = 0.034), FEV(1) (r(s) = 
      0.395, p = 0.031), and FEF(50%) (r(s) = -0.431, p = 0.020), i.e., the higher the
      bronchial NO output, the larger the decrease in PEF/FEV(1) /FEF(50%) . Alveolar
      NO concentrations correlated with the change in FEV(1) (r(s) = -0.439, p =
      0.015), FEF(50%) (r(s) = -0.454, p = 0.013), FEF(75%) (r(s) = -0.447, p = 0.017),
      and FVC (r(s) = -0.375, p = 0.045). For J'aw(NO) (TMAD), the correlations and p
      values were equal to those of J'aw(NO) , but, interestingly, CA(NO) (TMAD) had no
      significant correlations with any of the exercise-induced changes in lung
      function. CONCLUSION: The results showed that in atopic children and adolescents,
      increased bronchial NO output as well as J'aw(NO) (TMAD) were associated with
      EIB, while alveolar NO concentration (but not CA(NO) [TMAD]) correlated with the
      degree of obstruction in smaller airways induced by exercise challenge.

PMID- 22145649
TI  - The repertoire of G protein-coupled receptors in the human parasite Schistosoma
      mansoni and the model organism Schmidtea mediterranea.
AB  - BACKGROUND: G protein-coupled receptors (GPCRs) constitute one of the largest
      groupings of eukaryotic proteins, and represent a particularly lucrative set of
      pharmaceutical targets. They play an important role in eukaryotic signal
      transduction and physiology, mediating cellular responses to a diverse range of
      extracellular stimuli. The phylum Platyhelminthes is of considerable medical and
      biological importance, housing major pathogens as well as established model
      organisms. The recent availability of genomic data for the human blood fluke
      Schistosoma mansoni and the model planarian Schmidtea mediterranea paves the way
      for the first comprehensive effort to identify and analyze GPCRs in this
      important phylum. RESULTS: Application of a novel transmembrane-oriented approach
      to receptor mining led to the discovery of 117 S. mansoni GPCRs, representing all
      of the major families; 105 Rhodopsin, 2 Glutamate, 3 Adhesion, 2 Secretin and 5
      Frizzled. Similarly, 418 Rhodopsin, 9 Glutamate, 21 Adhesion, 1 Secretin and 11
      Frizzled S. mediterranea receptors were identified. Among these, we report the
      identification of novel receptor groupings, including a large and highly-diverged
      Platyhelminth-specific Rhodopsin subfamily, a planarian-specific Adhesion-like
      family, and atypical Glutamate-like receptors. Phylogenetic analysis was carried
      out following extensive gene curation. Support vector machines (SVMs) were
      trained and used for ligand-based classification of full-length Rhodopsin GPCRs,
      complementing phylogenetic and homology-based classification. CONCLUSIONS: Genome
      wide investigation of GPCRs in two platyhelminth genomes reveals an extensive and
      complex receptor signaling repertoire with many unique features. This work
      provides important sequence and functional leads for understanding basic flatworm
      receptor biology, and sheds light on a lucrative set of anthelmintic drug
      targets.

PMID- 22145650
TI  - Linear ion trap MS(n) of enzymatically synthesized 13C-labeled fructans revealing
      differentiating fragmentation patterns of beta (1-2) and beta (1-6) fructans and
      providing a tool for oligosaccharide identification in complex mixtures.
AB  - Fructans are polymeric carbohydrates, which play important roles as plant reserve
      carbohydrates and stress protectants, and are beneficial for human health and
      animal production. Fructans are formed by the addition of beta-d-fructofuranosyl
      units to sucrose, leading to very complex mixtures of 1-kestose based inulins, 6
      kestose linked levans, and 6G-kestose derived neoseries inulins and levans in
      cool season grasses such as Lolium perenne. The identification of isomeric
      fructan oligomers in chromatographic analysis of crude plant extracts is often
      hampered by the lack of authentic standards, and unambiguous peak assignment
      usually requires time-consuming analyses of purified fructan oligomers. We have
      developed a LC-MS(n) method for the separation and detection of fructan isomers
      and present here evidence for specific MS(n) fragmentation patterns associated
      with beta 1-2 (inulins) and beta 2-6 (levans) fructans. LC-MS(n) analysis of
      (13)C labeled fructan oligomers produced by L. perenne fructosyltransferases
      expressed in yeast has enabled us to account for the observed fragmentation
      patterns in terms of preferential cleavage of the glycosidic bond between O- and
      fructose C2 in both inulins and levans and to differentiate reducing-end from
      nonreducing end cross ring cleavages in levans. We propose that higher order MS
      fragmentation patterns can be used to distinguish between the two major classes
      of fructan, i.e., inulins and levans, without the need for authentic standards.

PMID- 22145652
TI  - AANP congratulates Dr. Loretta Ford on her induction to the National Women's Hall
      of Fame.

PMID- 22145651
TI  - Regulation of the inflammatory response of vascular endothelial cells by EPAC1.
AB  - Life-threatening diseases of the cardiovascular system, like atherosclerosis, are
      exacerbated by unwanted inflammation within the structures of large blood
      vessels. This inflammation involves increased permeability of the vascular
      endothelial cells (VECs) that form the lining of blood vessels, leading to
      exaggerated extravasation of blood components and accumulation of fluid in the
      extravascular space. This results in tissue dysfunction and increased secretion
      of chemokines that attract leukocytes and monocytes to the inflamed endothelium.
      Cyclic AMP is synthesized in VECs in response to endogenous Gs-coupled receptors
      and is known to limit cytokine action and reduce endothelial hyperpermeability
      induced by multiple pro-inflammatory stimuli. The mechanisms underlying this anti
      inflammatory action of cyclic AMP are now being elucidated and it is becoming
      clear that the cyclic AMP sensor, exchange protein activated by cyclic AMP
      (EPAC1), appears to play a key role in suppressing unwanted inflammation. EPAC1
      mediates at least three anti-inflammatory pathways in VECs by down-regulating
      inflammatory signalling through the induction of the suppressors of cytokine
      signalling 3 (SOCS-3) gene, limiting integrin-dependent vascular permeability and
      enhancing endothelial barrier function through the stabilization of VE-cadherin
      junctions. Given that manipulation of cellular cyclic AMP levels currently forms
      the basis of many effective pharmaceuticals and that EPAC1 is involved in
      multiple anti-inflammatory protective processes in VECs, does this make EPAC1 an
      attractive target for the development of activators capable of eliciting a
      coordinated programme of 'protection' against the development of endothelial
      dysfunction? Here we discuss whether EPAC1 represents an attractive therapeutic
      target for limiting endothelial dysfunction associated with cardiovascular
      diseases like atherosclerosis. LINKED ARTICLES This article is part of a themed
      section on Novel cAMP Signalling Paradigms. To view the other articles in this
      section visit http://dx.doi.org/10.1111/bph.2012.166.issue-2.

PMID- 22145653
TI  - Systemic lupus erythematosus: a genetic review for advanced practice nurses.
AB  - PURPOSE: To review the symptom presentation, genetic aspects, and available
      treatment options for individuals diagnosed with systemic lupus erythematosus
      (SLE). Primary care providers should be vigilant in identifying symptoms, which
      may be related to SLE, perform adequate assessment, and diagnostic testing in
      order to arrive at an early diagnosis. DATA SOURCES: Extensive literature review
      of textbook, clinical, medical, and nursing journals. CONCLUSIONS: Lupus is a
      multigenic autoimmune disease, which requires the clinician to be hypervigilant
      by collecting a thorough family history and performing a complete physical
      assessment of the patient. There is an array of treatment modalities, both
      experimental and proven therapies, which improve signs and symptoms associated
      with SLE. Numerous medications are available for symptom management: anti
      inflammatory agents for patients with musculoskeletal presentation, and steroids
      or antimalarials for those with more extensive organ involvement. IMPLICATIONS
      FOR PRACTICE: In SLE, the overall aim of management is to determine the extent of
      disease and prevent extensive organ involvement. Therefore, when diagnosed in a
      timely manner, most patients will survive and are able to manage their disease.

PMID- 22145654
TI  - Empowering the primary care provider to optimally manage mild traumatic brain
      injury.
AB  - PURPOSE: This article provides current, evidence-based information regarding the
      management of mild traumatic brain injuries for the primary-care provider. DATA
      SOURCES: Literature review of the evidence-based literature, including peer
      reviewed articles and reviews of published randomized controlled trials and
      clinical practice guidelines. CONCLUSIONS: There are lessons to learn from the
      civilian and military care of mild traumatic brain injuries. As acute injury
      management improves and more patients survive their trauma to live in the chronic
      care community setting, primary care clinicians will be responsible for providing
      and coordinating total care. A team approach is required to meet the unique
      clinical and personal challenges these patients face. IMPLICATIONS FOR PRACTICE:
      These patients are at risk of receiving suboptimal care once released to the
      community, in part due to an incomplete understanding of the condition by primary
      care providers. Other difficulties in recommending care for these patients
      include nonuniform clinical terminology, the lack of a uniform set of diagnostic
      criteria, and the lack of endorsed professional society guidelines. A clinical
      practice toolkit is provided to assist the primary care provider to optimize
      delivery of comprehensive care for this population in the community.

PMID- 22145655
TI  - Finding electronic information for health policy advocacy: a guide to improving
      search results.
AB  - PURPOSE: The success of advanced practice registered nurses' (APRNs') health
      policy advocacy depends on staying well informed about key issues. Searching for
      high-quality health policy information, however, can be frustrating and time
      consuming. Busy clinicians need strategies and tips to reduce information
      overload and to access synthesized research for evidence-based health policy.
      This article therefore offers APRNs practical guidelines and resources for
      searching electronic health policy information. DATA SOURCES: Scholarly databases
      and Internet sites. CONCLUSIONS: Electronic health policy information is
      generated by a wide variety of public and private organizations and disseminated
      in hundreds of journals and Web pages. Specialty search tools are needed to
      retrieve the unindexed gray literature, which includes government documents,
      agency reports, fact sheets, standards, and statistics not produced by commercial
      publishers. Further, Internet users need to examine search results with a
      critical eye for information quality. IMPLICATIONS FOR PRACTICE: Expertise in
      searching electronic health policy information is a prerequisite for developing
      APRNs' leadership in political arenas to influence health policy and the delivery
      of healthcare services.

PMID- 22145656
TI  - Preventing recurrent cerebrovascular events in patients with stroke or transient
      ischemic attack: the current data.
AB  - PURPOSE: To describe recurrent stroke in relation to the current data, treatment
      guidelines, diagnostic considerations, risk prevention, and management for the
      nurse practitioner (NP). DATA SOURCES: An extensive review of the scientific
      literature, clinical trials, and clinical guidelines. CONCLUSIONS: Recurrent
      stroke is a major health concern. A first ischemic cerebrovascular event or
      transient ischemic attack (TIA) is a risk factor for future strokes. IMPLICATIONS
      FOR PRACTICE: The risk of recurring stroke has been demonstrated in multiple
      studies, yet only approximately 5% of stroke patients receive appropriate therapy
      in a timely manner. The stroke or TIA workup should be completed quickly so that
      the appropriate treatments and interventions can be initiated to reduce the risk
      of an additional event. The etiology of the stroke and identification of personal
      risk factors are important because treatment depends on the specific stroke
      mechanism. A variety of antiplatelet trials have specific implications for stroke
      and recurrent stroke. Present treatments include aspirin, aspirin plus extended
      release dipyridamole and clopidogrel. The NP plays an important role in ongoing
      patient education about symptoms, the long-term management of the patient, and
      reduction of future stroke risk.

PMID- 22145657
TI  - A systematic review of advanced practice nurses' skin cancer assessment barriers,
      skin lesion recognition skills, and skin cancer training activities.
AB  - PURPOSE: Little is known about the skin cancer detection skills of advanced
      practice nurses (APNs). This systematic review of published literature seeks to
      describe (a) barriers to APNs' performance of skin examination, (b) APNs' ability
      to recognize suspicious skin lesions, and (c) APNs' skin cancer detection
      training activities. DATA SOURCES: The Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses statement guided the literature search (OVID Medline,
      Web of Science, and CINAHL databases) and interpretation of findings. Of the 136
      articles meeting criteria for selection, 12 pertaining to the purpose were
      selected for further review. CONCLUSIONS: Barriers to skin examination by APNs
      have been infrequently and inconsistently measured. Limited time to conduct skin
      examination is the most consistent barrier. APNs' ability to recognize and refer
      suspicious and benign lesions is inconsistent, but shows improvement after
      training. Few skin cancer training programs are available for APNs. IMPLICATIONS:
      Larger and more rigorously designed studies are needed to better determine APNs'
      barriers and facilitators to skin cancer assessment and their ability to
      recognize and appropriately refer potentially malignant skin lesions with a high
      level of sensitivity and specificity. Training to increase these skills needs to
      be targeted to APNs and occur at a much higher volume than current efforts.

PMID- 22145658
TI  - Quality of health care provided at a pediatric nurse-managed clinic.
AB  - PURPOSE: The purpose of this study is to assimilate evidence regarding quality of
      care received at nurse-managed clinics (NMCs), particularly a pediatric NMC that
      provides health care for the underserved pediatric population. DATA SOURCES: A
      nonexperimental design was used in this study. Quality of care data were
      collected at Trinity Nursing Center for Child Health (TNCCH), a pediatric NMC.
      Evidence included whether a pediatric NMC met selected national benchmark
      pediatric Healthcare Effectiveness and Data Information Set (HEDIS) quality
      indicators as well as HEDIS targets set by the Office of Medicaid Policy and
      Planning (OMPP) in Indiana. CONCLUSIONS: Findings suggest that TNCCH met or
      exceeded national HEDIS benchmark standards of care and targets set by OMPP. This
      study offers further evidence that NMCs provide a high quality of care.
      IMPLICATIONS FOR PRACTICE: Benefits of addressing the research question in this
      study include the preservation of the nurse-managed healthcare safety net,
      increased access to health care for the medically underserved population
      resulting in improved health outcomes, and evidence to suggest that NMCs can
      assist private practice physicians to support this population of patients.

PMID- 22145659
TI  - Knockdown of secreted protein acidic and rich in cysteine (SPARC) expression
      diminishes radiosensitivity of glioma cells.
AB  - Secreted protein acidic and rich in cysteine (SPARC) has been shown to play an
      important role in the promotion of glioma. In this study, we investigated the
      effects of downregulated SPARC expression on the radiosensitivity of human glioma
      U-87MG cells and its possible mechanism. With a small-interfering RNA (siRNA)
      expression plasmid vector targeting SPARC, we obtained the stably transfected
      cells in which the expression of SPARC was successfully downregulated. Then, the
      cells were irradiated with 60Co-gamma-rays and analyzed by several methods, such
      as clonogenic assay, flow cytometry, comet assay, and western blotting.
      Clonogenic assay showed that downregulation of SPARC expression enhanced cell
      survival after radiation. Flow cytometry analysis indicated that SPARCsiRNA
      decreased cell apoptosis responding to irradiation. Analysis of signaling
      molecules with western blotting showed that the level of Akt phosphorylation was
      increased in irradiated U-87MG/SPARCsiRNA cells. Further, cell-cycle analysis by
      flow cytometry showed enhanced G2 accumulation in U-87MG/SPARCsiRNA cells after
      irradiation. Comet assay revealed that SPARCsiRNA promoted the repair of
      radiation-induced DNA damage. Our results suggest that inhibition of SPARC
      expression may diminish the radiosensitivity of human glioma U-87MG cells. One of
      the mechanisms for this effect may be associated with the reduced cell apoptosis
      responding to radiation, which may be contributed by the phosphoinositide 3
      kinase/AKT pathway activation. Moreover, enhanced G2 accumulation and increased
      DNA repair may also account for the decreased radiosensitivity.

PMID- 22145660
TI  - Imaging, autoradiography, and biodistribution of (188)Re-labeled PEGylated
      nanoliposome in orthotopic glioma bearing rat model.
AB  - The (188)Re-labeled pegylated nanoliposome (abbreviated as (188)Re-Liposome) was
      prepared and evaluated for its potential as a theragnostic agent for glioma.
      (188)Re-BMEDA complex was loaded into the pegylated liposome core with pH 5.5
      ammonium sulfate gradient to produce (188)Re-Liposome. Orthotopic Fischer344/F98
      glioma tumor-bearing rats were prepared and intravenously injected with (188)Re
      Liposome. Biodistribution, pharmacokinetic study, autoradiography (ARG),
      histopathology, and nano-SPECT/CT imaging were conducted for the animal model.
      The result showed that (188)Re-Liposome accumulated in the brain tumor of the
      animal model from 0.28%+/-0.09% injected dose (ID)/g (n=3) at 1 hour to a maximum
      of 1.95%+/-0.35% ID/g (n=3) at 24 hours postinjection. The tumor-to-normal brain
      uptake ratio (T/N ratio) increased from 3.5 at 1 hour to 32.5 at 24 hours. Both
      ARG and histopathological images clearly showed corresponding tumor regions with
      high T/N ratios. Nano-SPECT/CT detected a very clear tumor image from 4 hours
      till 48 hours. This study reveals the potential of (188)Re-Liposome as a
      theragnostic agent for brain glioma.

PMID- 22145661
TI  - The course and prognosis of pemphigus in 47 Tunisian patients.
AB  - BACKGROUND: Pemphigus is a severe and life-threatening autoimmune bullous
      dermatosis. OBJECTIVE: We have analysed parameters that may influence prognosis
      of pemphigus (P). METHODS: It was a retrospective study (2002-2010), with
      pemphigus considered as severe if body surface involvement >= 30%. Disease
      control and relapse-free survival (Kaplan-Meier) were analysed and compared
      according to several parameters (P < 0.05). RESULTS: 47 cases of pemphigus were
      collected, mean age 51 years +/- 16.8 (F/H = 3.27). There were 30 pemphigus
      profundus and 17 superficial pemphigus. The median remission period was of 9
      months (1.2 months-5 years). The mean healing time was of 40 days (6 days-4
      months), which did not depend on type of P, its severity or infectious
      complications, whereas it was shorter in aged patient (>= 65 years) compared to
      non aged ones (P = 0.018). 36.2% of patients had relapsed. Relapses were
      significantly more frequently observed only in the presence of mucosal
      involvement at presentation (P = 0.015). The median overall 1st relapse-free
      survival was of 2.33 years. Only mucosal involvement at presentation was
      associated with a shorter median 1st relapse-free survival time (1.28 years vs. 3
      years) (P = 0.0017). Mortality rate was of 10.6% (n = 5); in four patients the
      death was directly related to pemphigus and occurred rapidly after the onset of
      lesions. CONCLUSION: Our study illustrates the poor prognosis of pemphigus by a
      long duration to disease control, a high initial dose of oral steroid, a high
      rate of relapse and a short remission period. Only mucosal involvement at
      presentation was identified as a poor prognostic factor.

PMID- 22145662
TI  - An all-photonic molecule-based D flip-flop.
AB  - The photochromic fluorescence switching of a fulgimide derivative was used to
      implement the first molecule-based D (delay) flip-flop device, which works based
      on the principles of sequential logic. The device operates exclusively with
      photonic signals and can be conveniently switched in repeated cycles.

PMID- 22145663
TI  - Naphthoquinone-like polyketide isolated from Streptomyces sp. RI-77 and its
      predicted biosynthetic pathway.
AB  - A novel naphthoquinone-like polyketide, JBIR-85 (1), with a unique skeleton and
      antioxidative activity was isolated from a culture of Streptomyces sp. RI-77. The
      planar structure of 1 was established on the basis of extensive NMR and MS
      analyses. The structure of 1 including the absolute configuration was established
      via X-ray crystallographic analysis. Since 1 exhibits a unique skeleton, we
      performed feeding experiments to reconfirm the structure and predict the
      biosynthetic pathway.

PMID- 22145664
TI  - Acute phase proteins in the diagnosis and prediction of cirrhosis associated
      bacterial infections.
AB  - BACKGROUND: Bacterial infections are common cause of morbidity and mortality in
      patients with cirrhosis. The early diagnosis of these infections is rather
      difficult. AIMS: To assess the accuracy of acute phase proteins in the
      identification of bacterial infections. METHODS: Concentration of C-reactive
      protein (CRP), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP),
      sCD14 and antimicrobial antibodies were measured in serum of 368 well
      characterized patients with cirrhosis of whom 139 had documented infection.
      Clinical data was gathered by reviewing the patients' medical charts. RESULTS:
      Serum levels of CRP, PCT and LBP were significantly higher in patients with
      clinically overt infections. Among the markers, CRP - using a 10 mg/L cut-off
      value- proved to be the most accurate in identifying patients with infection
      (AUC: 0.93). The accuracy of CRP, however, decreased in advanced stage of the
      disease, most probably because of the significantly elevated CRP levels in non
      infected patients. Combination of CRP and PCT increased the sensitivity and
      negative predictive value, compared with CRP on its own, by 10 and 5%
      respectively. During a 3-month follow-up period in patients without overt
      infections, Kaplan-Meier and proportional Cox-regression analyses showed that a
      CRP value of >10 mg/L (P = 0.035) was independently associated with a shorter
      duration to progress to clinically significant bacterial infections. There was no
      correlation between acute phase protein levels and antimicrobial seroreactivity.
      CONCLUSIONS: C-reactive protein on its own is a sensitive screening test for the
      presence of bacterial infections in cirrhosis and is also a useful marker to
      predict the likelihood of clinically significant bacterial infections in patients
      without overt infections.

PMID- 22145665
TI  - A photophysical study of the alpha-carboline (1-azacarbazole) aggregation
      process.
AB  - This paper reports a comprehensive photophysical study of the aggregation process
      of 1-azacarbazole, or alpha-carboline (9H-pyrido[2,3-b]indole), AC, in low polar
      aprotic solvents by using absorption, steady state and time-resolved fluorescence
      spectroscopic techniques. To ascertain the characteristics of the aggregation
      process we have studied the changes produced by the increase of the AC
      concentration and the decrease of the temperature on the absorption and
      fluorescence spectra of the AC monomer. Previously, to aid the interpretation of
      these results, the hydrogen bonding interactions of the AC monomer with pyridine,
      PY, and indole, IND, have been also analyzed. The results obtained from these
      studies reveal that, under our experimental conditions, AC does not form doubly
      hydrogen bonded cyclic dimers, (AC)(2), but singly hydrogen bonded open dimers,
      AC-AC, and open higher aggregates, (-AC-)(n). The formation of these species
      shifts to the red the absorption spectrum of the AC monomer and quenches its
      fluorescence.

PMID- 22145666
TI  - Metabolite profiling as a future tool in the prediction of type 2 diabetes
      mellitus.

PMID- 22145667
TI  - Multipotent stromal cell therapy for cavernous nerve injury-induced erectile
      dysfunction.
AB  - INTRODUCTION: Erectile dysfunction (ED) following radical prostatectomy (RP) is a
      result of inadvertent damage to the cavernous nerves that run close to the
      prostate capsula. The mechanisms behind the development of post-RP ED are
      increasingly recognized and include cavernosal fibrosis and cavernosal smooth
      muscle apoptosis, resulting from cavernous nerve degeneration due to neuropraxia.
      In recent years, cell-based therapies have received increasing attention
      regarding their potential for recovery of erectile function following cavernous
      nerve injury (CNI). Multipotent stromal cells (MSCs) are an attractive cell
      source for this application based on their regenerative potential and their
      clinical applicability. AIM: To review available evidence on the efficacy and
      mechanisms of action of MSC application for the treatment of ED, with an emphasis
      on ED following CNI. METHODS: A nonsystematic review was conducted on the
      available English literature between 1966 and 2011 on the search engines SciVerse
      sciencedirect, SciVerse-scopus, Google Scholar, and PubMed. RESULTS: MSCs from
      both bone marrow and adipose tissue have shown beneficial effects in a variety of
      animal models for ED. While MSC application in chronic disease models such as
      diabetes, aging, and hyperlipidemia may result in cell engraftment and possibly
      MSC differentiation, this observation has not been made in the acute CNI rat
      model. In the latter setting, MSC effects seem to be established by cell
      recruitment toward the major pelvic ganglion and local paracrine interaction with
      the host neural tissue. CONCLUSIONS: While the type of model may influence the
      mechanisms of action of this MSC-based therapy, MSCs generally display efficacy
      in various animal models for ED. Before translation to the clinic is established,
      various hurdles need to be overcome.

PMID- 22145668
TI  - A case of developmental language impairment in adolescence and adulthood.
AB  - We report the case of a 19-year-old female with a history of developmental
      language impairment. The subject's performance in accessing word forms, lexical
      semantics, syntactic abilities, and text comprehension was diagnosed. The results
      show a persisting multilevel impairment, especially with non-canonical and
      subordinated sentences, morphology, and narratives. Nevertheless a clear
      potential in compensating her difficulties for communicative purposes could be
      observed. There are only very few descriptions of German-speaking subjects with
      persisting language disorder. Our results underline previous findings of symptoms
      persisting into adolescence and adulthood. The symptomatology may be covert on
      superficial observation but is still of relevance to the participation of the
      individuals concerned. Further research on identifying language-specific clinical
      markers is needed to meet the requirements of this group of clients.

PMID- 22145669
TI  - New neptunium(V) borates that exhibit the alexandrite effect.
AB  - A new neptunium(V) borate, K[(NpO(2))B(10)O(14)(OH)(4)], was synthesized using
      boric acid as a reactive flux. The compound possesses a layered structure in
      which Np(V) resides in triangular holes, creating a hexagonal-bipyramidal
      environment around neptunium. This compound is unusual in that it exhibits the
      Alexandrite effect, a property that is typically restricted to neptunium(IV)
      compounds.

PMID- 22145671
TI  - Role of apathy in the effectiveness of weight management programmes.
AB  - AIMS: Obesity, which is at epidemic proportions in the USA, is associated with a
      higher risk of several co-morbid diseases including, cardiovascular disease,
      cancer and sleep apnea. Weight loss and weight maintenance programmmes are
      difficult to sustain for long term. Mental health problems such as apathy may be
      a major factor in patients unsuccessful in adhering to weight loss programmes. We
      propose that treating apathy will result in better weight loss in obese patients.
      METHODS: This was a randomized prospective pilot study. Obese patients (n = 101)
      were randomized in a 1:2:2 ratio to either (i) standard nutrition counselling; or
      (ii) the Department of Veterans Affairs weight loss programme called 'motivate
      obese veterans everywhere ' (MOVE); or (iii) methylphenidate treatment plus the
      MOVE programme together. The intervention was for 6 months (26 weeks). RESULTS:
      For the within groups analysis, the absolute changes in weight (kg) are as
      follows, for MOVE (mean: -1.84; 95% confidence interval (CI): -4.56 to 0.87; p =
      0.25), Methylphenidate (mean: -4.61; 95% CI: -7.90 to -1.33; p = 0.04), standard
      nutrition counselling (mean: -0.60; 95% CI: -2.59 to 1.39; p = 0.21), which
      indicates that although all three groups lost weight, only the methylphenidate
      group achieved statistical significance. The between group differences of the
      relative change in weight were not statistically different. The apathy evaluation
      score and the patient activation measure improved in all groups. CONCLUSION:
      Together these data suggest that treating apathy might be an important factor in
      the success of weight management programmes.

PMID- 22145670
TI  - Microtubules are organized independently of the centrosome in Drosophila neurons.
AB  - BACKGROUND: The best-studied arrangement of microtubules is that organized by the
      centrosome, a cloud of microtubule nucleating and anchoring proteins is clustered
      around centrioles. However, noncentrosomal microtubule arrays are common in many
      differentiated cells, including neurons. Although microtubules are not anchored
      at neuronal centrosomes, it remains unclear whether the centrosome plays a role
      in organizing neuronal microtubules. We use Drosophila as a model system to
      determine whether centrosomal microtubule nucleation is important in mature
      neurons. RESULTS: In developing and mature neurons, centrioles were not
      surrounded by the core nucleation protein gamma-tubulin. This suggests that the
      centrioles do not organize functional centrosomes in Drosophila neurons in vivo.
      Consistent with this idea, centriole position was not correlated with a specific
      region of the cell body in neurons, and growing microtubules did not cluster
      around the centriole, even after axon severing when the number of growing plus
      ends is dramatically increased. To determine whether the centrosome was required
      for microtubule organization in mature neurons, we used two approaches. First, we
      used DSas-4 centriole duplication mutants. In these mutants, centrioles were
      present in many larval sensory neurons, but they were not fully functional.
      Despite reduced centriole function, microtubule orientation was normal in axons
      and dendrites. Second, we used laser ablation to eliminate the centriole, and
      again found that microtubule polarity in axons and dendrites was normal, even 3
      days after treatment. CONCLUSION: We conclude that the centrosome is not a major
      site of microtubule nucleation in Drosophila neurons, and is not required for
      maintenance of neuronal microtubule organization in these cells.

PMID- 22145672
TI  - Biodegradable poly(vinyl alcohol)-polyethylenimine nanocomposites for enhanced
      gene expression in vitro and in vivo.
AB  - Use of cationic polymers as nonviral gene vectors has several limitations such as
      low transfection efficiency, high toxicity, and inactivation by serum. In this
      study, varying amounts of low molecular weight branched polyethylenimine 1.8 kDa
      (bPEI 1.8) were introduced on to a neutral polymer, poly(vinyl alcohol) (PVA), to
      bring in cationic charge on the resulting PVA-PEI (PP) nanocomposites. We
      rationalized that by introducing bPEI 1.8, buffering and condensation properties
      of the proposed nanocomposites would result in improved gene transfer capability.
      A series of PVA-PEI (PP) nanocomposites was synthesized using well-established
      epoxide chemistry and characterized by IR and NMR. Particle size of the PP/DNA
      complexes ranged between 120 to 135 nm, as determined by dynamic light scattering
      (DLS), and DNA retardation assay revealed efficient binding capability of PP
      nanocomposites to negatively charged nucleic acids. In vitro transfection of
      PP/DNA complexes in HEK293, HeLa, and CHO cells revealed that the best working
      formulation in the synthesized series, PP-3/DNA complex, displayed ~2-50-fold
      higher transfection efficiency than bPEIs (1.8 and 25 kDa) and commercial
      transfection reagents. More importantly, the PP/DNA complexes were stable over a
      period of time, along with their superior transfection efficiency in the presence
      of serum compared to serum-free conditions, retaining the nontoxic property of
      low molecular weight bPEI. The in vivo administration of PP-3/DNA complex in
      Balb/c mice showed maximum gene expression in their spleen. The study
      demonstrates the potential of PP nanocomposites as promising nonviral gene
      vectors for in vivo applications.

PMID- 22145673
TI  - Facile fabrication of super-hydrophobic nano-needle arrays via breath figures
      method.
AB  - Super-hydrophobic surfaces which have been fabricated by various methods such as
      photolithography, chemical treatment, self-assembly, and imprinting have gained
      enormous attention in recent years. Especially 2D arrays of nano-needles have
      been shown to have super-hydrophobicity due to their sharp surface roughness.
      These arrays can be easily generated by removing the top portion of the honeycomb
      films prepared by the breath figures method. The hydrophilic block of an
      amphiphilic polymer helps in the fabrication of the nano-needle arrays through
      the production of well-ordered honeycomb films and good adhesion of the film to a
      substrate. Anisotropic patterns with water wettability difference can be useful
      for patterning cells and other materials using their selective growth on the
      hydrophilic part of the pattern. However, there has not been a simple way to
      generate patterns with highly different wettability. Mechanical stamping of the
      nano-needle array with a polyurethane stamp might be the simplest way to
      fabricate patterns with wettability difference. In this study, super-hydrophobic
      nano-needle arrays were simply fabricated by removing the top portion of the
      honeycomb films. The maximum water contact angle obtained with the nano-needle
      array was 150 degrees . By controlling the pore size and the density of the
      honeycomb films, the height, width, and density of nano-needle arrays were
      determined. Anisotropic patterns with different wettability were fabricated by
      simply pressing the nano-needle array at ambient temperature with polyurethane
      stamps which were flexible but tough. Mechanical stamping of nano-needle arrays
      with micron patterns produced hierarchical super-hydrophobic structures.PACS:
      05.70.Np, 68.55.am, 68.55.jm.

PMID- 22145674
TI  - Inhibition of mammalian carbonic anhydrase isoforms I, II and VI with thiamine
      and thiamine-like molecules.
AB  - Here we determined the in vitro inhibitory effects of 5-(2-hydroxyethyl)-3,4
      dimethylthiazolium iodide (1), 3-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium
      chloride (2) and thiamine (3) on human erythrocyte carbonic anhydrase I, II
      isozymes (hCA I and hCA II) and secreted isoenzyme CA VI. K(I) values ranged from
      0.38 to 2.27 uM for hCA I, 0.085 to 0.784 uM for hCA II and 0.062 to 0.593 uM for
      hCA VI, respectively. The compounds displayed relatively strong actions on hCA
      II, in the same range as the clinically used sulfonamidesethoxzolamide,
      zonisamide and acetazolamide.

PMID- 22145675
TI  - Comparative ab initio study of CO adsorption on Sc(n) and Sc(n)O (n = 2-13)
      clusters.
AB  - Using a cluster model, we investigated the similarities and differences in
      chemical activity and the magnetic properties of Sc(n) clusters (n = 2-13) and
      their oxides, Sc(n)O, toward CO molecule adsorption via a spin-polarized density
      functional theory approach. The Sc(n) and Sc(n)O clusters have similar chemical
      activity at small sizes of n = 2-10, whereas remarkable differences are observed
      at large sizes of n = 11-13. More interestingly, different magnetic responses are
      found in the Sc(n) and Sc(n)O clusters with the presence of CO molecule: The
      magnetic moment is attenuated significantly for Sc(n) with n = 2, 4, 12, and 13,
      whereas for Sc(n)O, it is enhanced at n = 4 and 13 and is reduced for n = 7, 8,
      10, and 11. In particular, the magnetic moment remarkably increases from 7 MU(B)
      of Sc(13)O to 13 MU(B) of Sc(13)OCO, whereas it reduces from 19 MU(B) of Sc(13)
      to 5 MU(B) of Sc(13)CO.

PMID- 22145676
TI  - Birth weight is inversely associated with blood pressure and serum aldosterone
      and cortisol levels in children.
AB  - CONTEXT: Low birth weight has been independently associated with adult
      hypertension, and renin-angiotensin system (RAS) plays a role in this connection.
      OBJECTIVE: To characterize the associations between birth weight (BW) and serum
      aldosterone (SA), serum cortisol, plasma renin activity (PRA) and blood pressure
      (BP). DESIGN: Cross-sectional study. SUBJECTS: Children from the community born
      at a gestational age >32 weeks. METHODS: Systolic and diastolic BP indices (SBPi
      and DBPi) were calculated using the observed BP/50th percentile BP for gender,
      age and stature. BW was transformed to a standard deviation score (SDS) for
      gestational age, whereas SA, serum cortisol and PRA were transformed using the
      natural log. RESULTS: We selected 288 subjects between the ages of 4.9 and 15.5
      years (Females, 50%). After adjusting for body mass index (BMI) SDS and Tanner,
      multiple regression analysis revealed that BW (SDS) was both independently and
      inversely associated with the natural log of SA (beta = -0.065; P = 0.039), the
      natural log of serum cortisol (beta = -0.064; P = 0.009), SBPi (beta = -0.012; P
      = 0.020) and DBPi (beta = -0.023; P = 0.002). An association was not observed
      with PRA (P = 0.178) and aldosterone renin ratio (ARR) (P = 0.452). Serum
      cortisol levels were positively associated with SA (r = 0.125; P = 0.034), while
      an association with PRA (P = 0.251) and ARR (P = 0.052) was not observed.
      CONCLUSIONS: The results of this study demonstrate an inverse association between
      birth weight and blood pressure and serum aldosterone and cortisol levels. This
      association is independent of BMI and Tanner, suggesting foetal programming of
      the hypothalamic-pituitary-adrenal axis.

PMID- 22145677
TI  - A new efficient protocol for directed differentiation of retinal pigmented
      epithelial cells from normal and retinal disease induced pluripotent stem cells.
AB  - We describe a new, efficient protocol that involves the serial addition of
      noggin, basic fibroblast growth factor (bFGF), retinoic acid, and sonic hedgehog
      (Shh) for the differentiation of human induced pluripotent stem cells (hiPSC) to
      retinal pigmented epithelium (RPE) in a serum- and feeder-free adherent
      condition. hiPSC-RPE cells exhibited RPE morphology and specific molecular
      markers. Additionally, several hiPSC lines were generated from retinal-specific
      patients with Leber's congenital amaurosis, Usher syndrome, two patients with
      retinitis pigmentosa, and a patient with Leber's hereditary optic neuropathy. The
      RPE cells generated from these disease-specific hiPSCs expressed specific markers
      by the same RPE lineage-directed differentiation protocol. These findings
      indicate a new short-term, simple, and efficient protocol for differentiation of
      hiPSCs to RPE cells. Such specific retinal disease-specific hiPSCs offer an
      unprecedented opportunity to recapitulate normal and pathologic formation of
      human retinal cells in vitro, thereby enabling pharmaceutical screening, and
      potentially autologous cell replacement therapies for retinal diseases.

PMID- 22145678
TI  - Measuring the burden of herpes zoster and post herpetic neuralgia within primary
      care in rural Crete, Greece.
AB  - BACKGROUND: Research has indicated that general practitioners (GPs) have good
      clinical judgment in regards to diagnosing and managing herpes zoster (HZ) within
      clinical practice in a country with limited resources for primary care and
      general practice. The objective of the current study was to assess the burden of
      HZ and post herpetic neuralgia (PHN) within rural general practices in Crete,
      Greece. METHODS: The current study took place within a rural setting in Crete,
      Greece during the period of November 2007 to November 2009 within the catchment
      area in which the Cretan Rural Practice-based Research Network is operating. In
      total 19 GP's from 14 health care units in rural Crete were invited to
      participate, covering a total turnover patient population of approximately 25,
      000 subjects. For the purpose of this study an electronic record database was
      constructed and used as the main tool for monitoring HZ and PHN incidence. Stress
      related data was also collected with the use of the Short Anxiety Screening Test
      (SAST). RESULTS: The crude incidence rate of HZ was 1.4/1000 patients/year
      throughout the entire network of health centers and satellite practices, while
      among satellite practices alone it was calculated at 1.3/1000 patients/year.
      Additionally, the standardised incidence density within satellite practices was
      calculated at 1.6/1000 patients/year. In regards to the stress associated with HZ
      and PHN, the latter were found to have lower levels of anxiety, as assessed
      through the SAST score (17.4 +/- 3.9 vs. 21.1 +/- 5.7; p = 0.029). CONCLUSIONS:
      The implementation of an electronic surveillance system was feasible so as to
      measure the burden of HZ and PHN within the rural general practice setting in
      Crete.

PMID- 22145679
TI  - Elucidation of cell killing mechanism by comparative analysis of photoreactions
      on different types of bacteria.
AB  - The mechanism of biocidal action of nano titania on Escherichia coli and
      Staphylococcus aureus has been evaluated by various biochemical techniques like
      lipid peroxidation, hydrolysis of orthonitrophenol beta-D-galactopyranoside,
      estimation of protein-amino acid and bacterial nucleic acids leakage into
      solution, in addition to morphology studies by electron microscopy (TEM and SEM)
      and K(+) ion leakage by inductively coupled plasma optical emission spectrometry.
      The active anatase phase of nano titania has been synthesized by sol-gel and
      pulverization techniques to obtain particle sizes averaging around 11 nm. The
      nano semiconductor with a bandgap of 3.2 eV responds well to the UV source to
      liberate reactive oxygen species (ROS). Gram negative bacteria easily succumb to
      the ROS at a faster rate than gram-positive bacteria with an observable
      difference in the mode of attack. The use of analytical techniques revealed the
      release of peroxidized lipid (26 nmol mL(-1) ) and protein content (370 MUg mL(
      1)) with a K(+) ion concentration of 22 000 ppb on complete destruction of E.
      coli.

PMID- 22145680
TI  - Triangulating health expenditure estimates from different data sources in
      developing countries: the case of Pakistan's private health expenditure.
AB  - This article deals with the accuracy of statistical records used for political
      decision making and international comparative analysis. In developing countries,
      even major macroeconomic indicators can include data inadequacies and
      methodological differences in data generation between statistical agencies.
      Existing data show that total health expenditure as a percentage of GDP is about
      50% lower in Pakistan than in other low-income countries (LIC). To determine
      whether these results reflect the actual situation in Pakistan or whether they
      are due to statistical error, Pakistan produced National Health Accounts (NHA)
      for the first time in 2009 to assess health spending in 2005-6. Improved NHA
      estimates are also being made for 2007-8, which will be based on the following:
      public expenditure data published with time lags; survey results for 2007-8; and
      multivariate analyses of data from 2010 and 2011 surveys on health-specific out
      of-pocket (OOP) expenditure, healthcare providers, non-profit institutions and
      census data on autonomous bodies and large hospitals. Since these data are not
      yet available, a best estimate of health expenditure has to be made to support
      policy decision making and to provide a point of comparison for future NHA
      results. Health expenditure data are available from different data sources and
      estimates have been made by applying different methods, leading to a range of
      health spending estimates. As a result of this diversity of estimates and data,
      each with its own inaccuracies or gaps, there was a clear need to triangulate the
      available information and to identify a best possible estimate. This article
      compares estimates of household health expenditure from different sources, such
      as the Household Integrated Economic Survey, the Family Budget Survey and
      National Accounts (NA). The analysis shows that health expenditure figures for
      Pakistan have been underestimated by both WHO and the NHA. An adjusted estimate
      shows OOP spending to be twice as high as previously thought. Previous per capita
      total health expenditure estimates ranged from $US16 to $US19. The revised
      estimate showed per capita total health expenditure to be $US33, based on NA
      data. This puts Pakistan in a different position in international comparisons,
      with health expenditure exceeding the level of India ($US32.5) and the average of
      all LIC ($US24.5). Methodological differences in estimating expenditure and the
      multiple and conflicting estimates might cause stakeholders to make potentially
      adverse or even erroneous policy decisions on the allocation of resources.
      Because policy makers make decisions based on the estimates provided, the
      provision of a best estimate, made following a review of the advantages and
      limitations of existing sources and methods, is key.

PMID- 22145681
TI  - Microfabricated linear hydrogel microarray for single-nucleotide polymorphism
      detection.
AB  - A platform is developed for rapid, multiplexed detection of single-nucleotide
      polymorphisms using gels copolymerized with oligonucleotide capture probes in a
      linear microchannel array. DNA samples are analyzed by electrophoresis through
      the linear array of gels, each containing 20-40 MUM of a unique oligonucleotide
      capture probe. Electrophoresis of target DNA through the capture sites and the
      high concentration of capture probes within the gels enables significantly
      shorter incubation times than standard surface DNA microarrays. These factors
      also result in a significant concentration of target within the gels, enabling
      precise analysis of as little as 0.6 femtomoles of DNA target. Differential
      melting of perfectly matched and mismatched targets from capture probes as a
      function of electric field and temperature enables rapid, unambiguous
      identification of single-nucleotide polymorphisms.

PMID- 22145682
TI  - Sources, concentrations, and risks of naphthalene in indoor and outdoor air.
AB  - Naphthalene is a ubiquitous pollutant, and very high concentrations are sometimes
      encountered indoors when this chemical is used as a pest repellent or deodorant.
      This study describes the distribution and sources of vapor-phase naphthalene
      concentrations in four communities in southeast Michigan, USA. Outdoors,
      naphthalene was measured in the communities and at a near-road site. Indoors,
      naphthalene levels were characterized in 288 suburban and urban homes. The median
      outdoor concentration was 0.15 MUg/m(3), and a modest contribution from rush-hour
      traffic was noted. The median indoor long-term concentration was 0.89 MUg/m(3),
      but concentrations were extremely skewed and 14% of homes exceeded 3 MUg/m(3),
      the chronic reference concentration for non-cancer effects, 8% exceeded 10
      MUg/m(3), and levels reached 200 MUg/m(3). The typical excess individual lifetime
      cancer risk was about 10(-4) and reached 10(-2) in some homes. Important sources
      include naphthalene's use as a pest repellent and deodorant, migration from
      attached garages and, to lesser extents, cigarette smoke and vehicle emissions.
      Excessive use as a repellent caused the highest concentrations. Naphthalene
      presents high risks in a subset of homes, and policies and actions to reduce
      exposures, for example, sales bans or restrictions, improved labeling, and
      consumer education, should be considered. PRACTICAL IMPLICATIONS: Long-term
      average concentrations of naphthalene in most homes fell into the 0.2-1.7
      MUg/m(3) range reported as representative in earlier studies. The highly skewed
      distribution of concentrations results in a subset of homes with elevated
      concentrations and health risks that greatly exceed US EPA and World Health
      Organization (WHO) guidelines. The most important indoor source is the use of
      naphthalene as a pest repellant or deodorant; secondary sources include presence
      of an attached garage, cigarette smoking, and outdoor sources. House-to-house
      variation was large, reflecting differences among the residences and naphthalene
      use practices. Stronger policies and educational efforts are needed to eliminate
      or modify indoor usage practices of this chemical.

PMID- 22145683
TI  - The encapsulation of an amphiphile into polystyrene microspheres of narrow size
      distribution.
AB  - Encapsulation of compounds into nano- or microsized organic particles of narrow
      size distribution is of increasing importance in fields of advanced imaging and
      diagnostic techniques and drug delivery systems. The main technology currently
      used for encapsulation of molecules within uniform template particles while
      retaining their size distribution is based on particle swelling methodology,
      involving penetration of emulsion droplets into the particles. The swelling
      method, however, is efficient for encapsulation only of hydrophobic compounds
      within hydrophobic template particles. In order to be encapsulated, the molecules
      must favor the hydrophobic phase of an organic/aqueous biphasic system, which is
      not easily achieved for molecules of amphiphilic character.The following work
      overcomes this difficulty by presenting a new method for encapsulation of
      amphiphilic molecules within uniform hydrophobic particles. We use hydrogen
      bonding of acid and base, combined with a pseudo salting out effect, for the
      entrapment of the amphiphile in the organic phase of a biphasic system. Following
      the entrapment in the organic phase, we demonstrated, using fluorescein and
      (antibiotic) tetracycline as model molecules, that the swelling method usually
      used only for hydrophobes can be expanded and applied to amphiphilic molecules.

PMID- 22145684
TI  - Influence of baseline serum testosterone on changes in body composition in
      response to testosterone therapy.
AB  - INTRODUCTION: The prognostic value of serum total testosterone (TT) prior to
      treatment has not been investigated. AIM: This study was performed to determine
      how baseline TT influences changes in body composition in men undergoing
      testosterone therapy (TTh). MAIN OUTCOME MEASURES: Response to TTh in a clinical
      population of men with symptomatic testosterone deficiency (TD). METHODS:
      Retrospective case series of 58 men with TD were treated with TTh. All were naive
      to previous TTh. Men were stratified into two groups: group 1 (N = 38) consisted
      of men with baseline TT > 300 ng/dL (10.4 nmol/L) and group 2 (N = 20) consisted
      of men with total TT < 300 ng/dL. Men in group 1 were diagnosed with TD on the
      basis of low values of free testosterone (FT) < 1.5 ng/dL (19.3 pmol/L). Dual
      energy X-ray absorptiometry was performed at baseline and follow-up (6.9 +/- 4
      months) to assess regional and whole body. RESULTS: At baseline, both groups had
      similar lean mass (LM) and fat mass (FM), but percentage of trunk FM and
      percentage of total FM were significantly higher in group 2. Both groups
      demonstrated similar increases in LM for arms, legs, and total body. Percentage
      of total FM significantly decreased in both groups. CONCLUSIONS: Baseline
      severity of symptomatic TD influences body composition. Similar changes in LM and
      FM were seen with TTh regardless of baseline severity in TD. Men with TT > 300
      ng/dL demonstrated significant positive changes in body composition. The
      similarity in objective response to TTh in these two groups provides support for
      the value of FT in the assessment of men with symptoms suggestive of TD.

PMID- 22145690
TI  - Imaging diagnosis--acquired pectus excavatum secondary to laryngeal paralysis in
      a dog.
AB  - A 13-year-old neutered female Labrador retriever had inspiratory dyspnea
      secondary to bilateral laryngeal paralysis. Radiographically, there was pectus
      excavatum with a mediastinal shift to the right. Arytenoid lateralization was
      performed, relieving the upper respiratory obstruction, and the sternal deformity
      also resolved. Chronic upper respiratory obstruction should be considered in dogs
      with pectus excavatum. Furthermore, correction of upper respiratory obstruction
      has the potential to result in resolution of pectus excavatum.

PMID- 22145691
TI  - Metastatic melanoma: spontaneous occurrence of auto antibodies is a good
      prognosis factor in a prospective cohort.
AB  - BACKGROUND: Melanoma is an immunogenic tumour type frequently associated with
      spontaneous auto-immune manifestations such as spontaneous regression, vitiligo
      like reactions or auto-immune retinopathy, which seem to be associated with
      better prognosis. OBJECTIVES: The aim of this prospective study was to evaluate
      the correlation between spontaneous autoimmunity and survival in patients with
      stage IV melanoma. METHODS: From 2007 to 2008, 103 patients were studied with
      antithyroid and antinuclear auto antibody assays performed every 6 months. Any
      detectable occurrence of a spontaneous self antibody (SpSA) at the upper
      detection limit, at least for one assay, was considered to be a biological marker
      of autoimmunity. RESULTS: Univariate and multivariate analyses confirmed
      significantly longer survival in the absence of known primary melanoma (P =
      0.044) and in the presence of marker of biologic autoimmunity, independently of
      previous immunotherapy (P = 0.045). CONCLUSIONS: This prospective and comparative
      study is, to our knowledge, the first to report the frequency of SpSA in stage IV
      melanoma. Our results suggest that spontaneous autoimmunity, through a rupture of
      self-tolerance, is a good prognostic factor in a subgroup of patients with stage
      IV melanoma.

PMID- 22145692
TI  - Vertical bone augmentation with simultaneous dental implantation using crestal
      biomaterial rings: a rabbit animal study.
AB  - BACKGROUND: Ceramic biomaterial blocks like hydroxyl apatite are too brittle for
      simple simultaneous vertical augmentation and dental implant placement.
      Biological scaffolds of xenogenic or allogenic origin are known to be
      advantageous. PURPOSE: The aim of this study was the proof of principle for
      combined vertical bone augmentation and dental implantation with marginal cuffs
      made of biological scaffolds with interconnecting porous system and titanium
      dental implants. MATERIALS AND METHODS: Cylindrical porcine biomaterial rings
      (processed, mineralized bone matrix) were placed in combination with titanium
      dental implants in the tibia model using six chinchilla bastard rabbits (n = 12
      samples). Histological examination included undecalcified histological
      examination with toluidine blue staining and fluorescence microscopy. Animals
      were sacrificed after 30 days. RESULTS: The results showed bony healing in the
      scaffolds with immature bone tissue ingrowth following the trabecular structure,
      showing lamellar cancellous bone healing. Fluorescence microscope showed
      analogous results. CONCLUSION: The biological scaffold proved a biocompatibility
      in a xenogenic setting. The vertical bone augmentation with simultaneous
      implantation was successful and proved the feasibility of the concept.

PMID- 22145693
TI  - Intestinal obstruction following use of laparoscopic barbed suture: a new
      complication with new material?
AB  - Small bowel obstruction is a common pathology. Among the various etiologies,
      foreign material has been incriminated as a possible but uncommon cause.
      Recently, barbed suture has been successfully introduced in various surgical
      fields and has been reported as safe as standard suture. We report herein a case
      of intestinal obstruction due to the laparoscopic use of barbed suture during a
      promontofixation. Barbed suture has the risk of entrapping the small bowel. The
      surgeon should keep in mind this hypothetical problem and a high index of
      suspicion is needed to diagnose and treat quickly this potentially severe
      complication.

PMID- 22145694
TI  - Simple methanesulfonates are hydrolyzed by the sulfatase carbonic anhydrase
      activity.
AB  - The possible sulfatase activity of several carbonic anhydrase (CA, EC 4.2.1.1)
      isoforms have been investigated with a series of synthesized methanesulfonate
      derivatives of phenols. Four alpha-CA isozymes, i.e. hCA I, hCA II, hCA IV and
      hCA VI (h = human isoform), were included in the study. We evidenced that the
      original sulfonate esters are being hydrolyzed effectively to the corresponding
      phenols which there after act as CA inhibitors. The K(I)-s of these compounds
      ranged from 10.24 to 4012 uM against hCA I, 0.10 to 35.42 uM against hCA II, 0.49
      to 45.06 uM against hCA IV and 3.27 to 608 uM against CA VI, respectively. The
      relevant sulfatase activity of CA with these esters is amazing considering the
      fact that 4-nitrophenyl-sulfate, an activated ester, is not a substrate of these
      enzymes.

PMID- 22145695
TI  - Factors associated with improvement in guideline-based use of ICDs in eligible
      heart failure patients.
AB  - BACKGROUND: IMPROVE HF, a 24-month performance improvement initiative for
      outpatient cardiology and multispecialty practices, demonstrated significant
      improvement in guideline-based use of implantable cardioverter-defibrillators
      (ICDs) for patients with heart failure (HF). We investigated patient, physician,
      and practice factors associated with improvements in ICD use. METHODS: Patients
      with HF or postmyocardial infarction (MI) left ventricular systolic dysfunction
      who met eligibility criteria for ICDs at baseline and 24 months were analyzed.
      Multivariate analyses were performed to identify patient, physician, and practice
      characteristics associated with greater improvement in ICD therapy rates from
      baseline to 24 months. RESULTS: There were 4,058 patients eligible for ICD
      therapy at baseline and 24 months, with 2,600 (64.1%) treated at baseline and
      3,361 (82.8%) treated at 24 months (+18.7%, P < 0.001). Practice heterogeneity in
      ICD use was significantly decreased after implementation of the performance
      improvement initiative. Characteristics independently associated with improvement
      in use of ICD therapy included race, history of MI, presence of edema, QRS
      duration, months since last measured left ventricular ejection fraction, and
      number of physicians in the practice. Improvement in ICD use was independent of
      other patient, physician, and practice characteristics, including age and sex.
      CONCLUSIONS: The IMPROVE HF performance improvement initiative was associated
      with substantially improved adherence to guideline-recommended ICD therapy.
      Certain patient and practice characteristics, including race, history of MI,
      edema, QRS duration, and number of physicians in the practice, were independently
      associated with improvement in ICD use. These findings highlight the need for
      ongoing quality improvement monitoring and performance improvement activities.

PMID- 22145696
TI  - Direct determination of the hydrogen bonding arrangement in anhydrous beta-chitin
      by neutron fiber diffraction.
AB  - The hydrogen bonding arrangement in anhydrous beta-chitin, a homopolymer of N
      acetylglucosamine, was directly determined by neutron fiber diffraction. Data
      were collected from a sample prepared from the bathophilous tubeworm 
      Lamellibrachia satsuma  in which all labile hydrogen atoms had been replaced by
      deuterium. Initial positions of deuterium atoms on hydroxyl and acetamide groups
      were directly located in Fourier maps synthesized using phases calculated from
      the X-ray structure and amplitudes measured from the neutron data. The hydrogen
      bond arrangement in the refined structure is in general agreement with
      predictions based on the X-ray structure: O3 donates a hydrogen bond to the O5
      ring oxygen atom of a neighboring residue in the same chain; N2 and O6 donate
      hydrogen bonds to the same carbonyl oxygen O7 of an adjacent chain. The
      intramolecular O3...O5 hydrogen bond has the most energetically favorable
      geometry with a hydrogen to acceptor distance of 1.77 A and a hydrogen bond angle
      of 171 degrees .

PMID- 22145697
TI  - New vanadium selenites: centrosymmetric Ca2(VO2)2(SeO3)3(H2O)2, Sr2(VO2)2(SeO3)3,
      and Ba(V2O5)(SeO3), and noncentrosymmetric and polar A4(VO2)2(SeO3)4(Se2O5) (A =
      Sr2+ or Pb2+).
AB  - Five new vanadium selenites, Ca(2)(VO(2))(2)(SeO(3))(3)(H(2)O)(2),
      Sr(2)(VO(2))(2)(SeO(3))(3), Ba(V(2)O(5))(SeO(3)),
      Sr(4)(VO(2))(2)(SeO(3))(4)(Se(2)O(5)), and Pb(4)(VO(2))(2)(SeO(3))(4)(Se(2)O(5)),
      have been synthesized and characterized. Their crystal structures were determined
      by single crystal X-ray diffraction. The compounds exhibit one- or two
      dimensional structures consisting of corner- and edge-shared VO(4), VO(5), VO(6),
      and SeO(3) polyhedra. Of the reported materials,
      A(4)(VO(2))(2)(SeO(3))(4)(Se(2)O(5)) (A = Sr(2+) or Pb(2+)) are
      noncentrosymmetric (NCS) and polar. Powder second-harmonic generation (SHG)
      measurements revealed SHG efficiencies of approximately 130 and 150 * alpha
      SiO(2) for Sr(4)(VO(2))(2)(SeO(3))(4)(Se(2)O(5)) and
      Pb(4)(VO(2))(2)(SeO(3))(4)(Se(2)O(5)), respectively. Piezoelectric charge
      constants of 43 and 53 pm/V, and pyroelectric coefficients of -27 and -42
      MUC/m(2).K at 70  degrees C were obtained for
      Sr(4)(VO(2))(2)(SeO(3))(4)(Se(2)O(5)) and Pb(4)(VO(2))(2)(SeO(3))(4)(Se(2)O(5)),
      respectively. Frequency dependent polarization measurements confirmed that the
      materials are not ferroelectric, that is, the observed polarization cannot be
      reversed. In addition, the lone-pair on the Se(4+) cation may be considered as
      stereo-active consistent with calculations. For all of the reported materials,
      infrared, UV-vis, thermogravimetric, and differential thermal analysis
      measurements were performed. Crystal data: Ca(2)(VO(2))(2)(SeO(3))(3)(H(2)O)(2),
      orthorhombic, space group Pnma (No. 62), a = 7.827(4) A, b = 16.764(5) A, c =
      9.679(5) A, V = 1270.1(9) A(3), and Z = 4; Sr(2)(VO(2))(2)(SeO(3))(3),
      monoclinic, space group P2(1)/c (No. 12), a = 14.739(13) A, b = 9.788(8) A, c =
      8.440(7) A, beta = 96.881(11) degrees , V = 1208.8(18) A(3), and Z = 4;
      Ba(V(2)O(5))(SeO(3)), orthorhombic, space group Pnma (No. 62), a = 13.9287(7) A,
      b = 5.3787(3) A, c = 8.9853(5) A, V = 673.16(6) A(3), and Z = 4;
      Sr(4)(VO(2))(2)(SeO(3))(4)(Se(2)O(5)), orthorhombic, space group Fdd2 (No. 43), a
      = 25.161(3) A, b = 12.1579(15) A, c = 12.8592(16) A, V = 3933.7(8) A(3), and Z =
      8; Pb(4)(VO(2))(2)(SeO(3))(4)(Se(2)O(5)), orthorhombic, space group Fdd2 (No.
      43), a = 25.029(2) A, b = 12.2147(10) A, c = 13.0154(10) A, V = 3979.1(6) A(3),
      and Z = 8.

PMID- 22145698
TI  - Linagliptin monotherapy provides superior glycaemic control versus placebo or
      voglibose with comparable safety in Japanese patients with type 2 diabetes: a
      randomized, placebo and active comparator-controlled, double-blind study.
AB  - AIMS: To evaluate the efficacy and safety of linagliptin 5 and 10 mg vs. placebo
      and voglibose in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS:
      This study enrolled patients with inadequately controlled T2DM who were
      previously treated with one or two oral antidiabetics or were drug naIve. After a
      2 to 4-week washout and placebo run-in, 561 patients were randomized (2 : 2 : 2 :
      1) to double-blind treatment with linagliptin 5 or 10 mg qd, voglibose 0.2 mg tid
      or placebo. The primary endpoint was the change from baseline in haemoglobin A1c
      (HbA1c) with linagliptin vs. placebo after 12 weeks and vs. voglibose after 26
      weeks. RESULTS: Baseline characteristics were well balanced across treatment
      groups (overall mean HbA1c was 8.01%). The adjusted mean (95% confidence
      interval) treatment differences at week 12 were -0.87% (-1.04, -0.70; p < 0.0001)
      and -0.88% (-1.05, -0.71; p < 0.0001) for linagliptin 5 and 10 mg vs. placebo and
      at week 26 were -0.32% (-0.49, -0.15; p = 0.0003) and -0.39% (-0.56, -0.21; p <
      0.0001) for linagliptin 5 and 10 mg vs. voglibose. At week 12, mean HbA1c was
      7.58, 7.48 and 8.34% in patients receiving linagliptin 5 mg, linagliptin 10 mg
      and placebo, respectively. At week 26, mean HbA1c was 7.63% with linagliptin 5
      mg, 7.50% with linagliptin 10 mg and 7.91% with voglibose. Drug-related adverse
      event rates were comparable across treatment groups over 12 weeks (9.4%
      linagliptin 5 mg, 8.8% linagliptin 10 mg and 10.0% placebo) and 26 weeks (11.3%
      linagliptin 5 mg, 10.6% linagliptin 10 mg and 18.5% voglibose). There were no
      documented cases of hypoglycaemia. CONCLUSIONS: Linagliptin showed superior
      glucose-lowering efficacy and comparable safety and tolerability to both placebo
      and voglibose in Japanese patients with T2DM.

PMID- 22145699
TI  - Analysis of optical absorption in GaAs nanowire arrays.
AB  - In this study, the influence of the geometric parameters on the optical
      absorption of gallium arsenide [GaAs] nanowire arrays [NWAs] has been
      systematically analyzed using finite-difference time-domain simulations. The
      calculations reveal that the optical absorption is sensitive to the geometric
      parameters such as diameter [D], length [L], and filling ratio [D/P], and more
      efficient light absorption can be obtained in GaAs NWAs than in thin films with
      the same thickness due to the combined effects of intrinsic antireflection and
      efficient excitation of resonant modes. Optimized geometric parameters are
      obtained as follows: D = 180 nm, L = 2 MUm, and D/P = 0.5. Meanwhile, the
      simulation on the absorption of GaAs NWAs for oblique incidence has also been
      carried out. The underlying physics is discussed in this work.PACS: 81.07.Gf
      nanowires; 81.05.Ea III-V semiconductors; 88.40.hj efficiency and performance of
      solar cells; 73.50.Pz photoconduction and photovoltaic effects.

PMID- 22145700
TI  - Bottom-up view of water network-mediated CO2 reduction using cryogenic cluster
      ion spectroscopy and direct dynamics simulations.
AB  - The transition states of a chemical reaction in solution are generally accessed
      through exchange of thermal energy between the solvent and the reactants. As
      such, an ensemble of reacting systems approaches the transition state
      configuration of reactant and surrounding solvent in an incoherent manner that
      does not lend itself to direct experimental observation. Here we describe how gas
      phase cluster chemistry can provide a detailed picture of the microscopic
      mechanics at play when a network of six water molecules mediates the trapping of
      a highly reactive "hydrated electron" onto a neutral CO(2) molecule to form a
      radical anion. The exothermic reaction is triggered from a metastable
      intermediate by selective excitation of either the reactant CO(2) or the water
      network, which is evidenced by the evaporative decomposition of the product
      cluster. Ab initio molecular dynamics simulations of energized CO(2).(H(2)O)(6)(
      ) clusters are used to elucidate the nature of the network deformations that
      mediate intracluster electron capture, thus revealing the detailed solvent
      fluctuations implicit in the Marcus theory for electron-transfer kinetics in
      solution.

PMID- 22145701
TI  - Adolescents with congenital adrenal hyperplasia because of 21-hydroxylase
      deficiency have vascular dysfunction.
AB  - CONTEXT: Patients with congenital adrenal hyperplasia (CAH) because of 21
      hydroxylase deficiency have multiple vascular risk factors. Young adults with CAH
      have increased intima media thickness, but there have been no studies of vascular
      function and structure in children with CAH. OBJECTIVE: To establish whether
      children with CAH have reduced vascular function and increased carotid intima
      media thickness (cIMT) when compared to healthy and obese children. DESIGN AND
      PATIENTS: Cross-sectional study of 14 patients (14.8 years +/- 3.2, seven boys)
      with CAH secondary to 21-hydroxylase deficiency compared to 28 obese and 53
      healthy controls. MEASUREMENTS: All subjects had assessment of endothelial
      function flow-mediated dilatation, (FMD), smooth muscle function glyceryl tri
      nitrate dilatation (GTN) and cIMT. Anthropometric data, resting blood pressure
      and biochemical variables were also measured. RESULTS: Congenital adrenal
      hyperplasia subjects had significantly reduced FMD (4.5 +/- 3.0% vs 7.5 +/- 5.2%;
      P = 0.04) and GTN (17.2 +/- 1.6% vs 28.4 +/- 8.4%; P < 0.001) when compared to
      controls and the impairment was comparable to the obese cohort. There was no
      significant difference in cIMT between groups. CAH subjects had increased
      homoeostasis model of assessment-insulin resistance [HOMA-IR 2.5 (0.2-2.9) vs 1.8
      (0.5-4.2); P = 0.04], waist-to-height ratio (0.47 +/- 0.05 vs 0.44 +/- 0.04; P =
      0.02) and higher systolic blood pressure Z score (0.29 +/- 0.9 vs-0.24 +/- 0.64,
      P = 0.01) compared to healthy controls but not when compared to obese controls.
      CONCLUSIONS: Subjects with CAH have evidence of vascular dysfunction by
      adolescence.

PMID- 22145702
TI  - The genetic interface between gestational diabetes and type 2 diabetes.
AB  - OBJECTIVE: Although the Western diet and lifestyle has contributed to an increase
      in the prevalence of gestational diabetes (GDM) worldwide, genetic predisposition
      also plays an important role. This article reviews the current state of knowledge
      regarding the genetic interface between type 2 diabetes (T2D) and GDM. METHODS:
      Review of the current literature on genetics of T2D and GDM. RESULTS: Maturity
      Onset Diabetes of the Young (MODY) due to glucokinase mutations may account for
      as much as 5% of GDM patients. Knowledge of both maternal and fetal genotypes may
      be useful for individualizing glycemic goals during pregnancy in families
      harboring these mutations. Of the 38 common T2D susceptibility variants
      identified to date, several are also associated with GDM. Presumably, these
      mutations increase GDM risk through decreased ability of beta-cells to compensate
      for the insulin resistance associated with pregnancy. The effect of these alleles
      on risk for GDM is modest (odds ratios (odds ratio (OR)~1.1-1.6); thus, they
      individually are poorly predictive. CONCLUSIONS: Future studies must concentrate
      on understanding the biological underpinnings of known T2D risk alleles and the
      discovery of new alleles for both GDM and T2D. These insights may lead to more
      effective strategies for preventing and treating GDM.

PMID- 22145703
TI  - A comparison of human smooth muscle and mesenchymal stem cells as potential cell
      sources for tissue-engineered vascular patches.
AB  - In pediatric patients requiring vascular reconstruction, the development of a
      cell-based tissue-engineered vascular patch (TEVP) has great potential to
      overcome current issues with nonliving graft materials. Determining the optimal
      cell source is especially critical to TEVP success. In this study, we compared
      the ability of human aortic smooth muscle cells (HuAoSMCs) and human mesenchymal
      stem cells (hMSCs) to form cell sheets on thermoresponsive poly(N
      isopropylacrylamide) (PIPAAm) substrates. hMSCs treated with transforming growth
      factor beta 1 (TGFbeta1) and ascorbic acid (AA) had higher expression of SMC
      specific proteins compared to HuAoSMCs. hMSCs also had larger cell area and grew
      to confluence more quickly on PIPAAm than did HuAoSMCs. hMSCs typically formed
      cell sheets in 2-3 weeks and had greater wet tissue weight and collagen content
      compared with HuAoSMC sheets, which generally required growth for up to 5 weeks.
      Assays for calcification and alkaline phosphatase activity revealed that the
      osteogenic potential of TGFbeta1+AA-treated hMSCs was low; however, Alcian Blue
      staining suggested high chondrogenic behavior of TGFbeta1+AA-treated hMSCs.
      Although hMSCs are promising for cell-based TEVPs in their ability to form robust
      tissue with significant extracellular matrix content, improved control over hMSC
      behavior will be required for long-term TEVP success.

PMID- 22145704
TI  - SERPINE2 haplotype as a risk factor for panlobular type of emphysema.
AB  - BACKGROUND: SERPINE2 (serpin peptidase inhibitor, clade E, member 2) has
      previously been identified as a positional candidate gene for chronic obstructive
      pulmonary disease (COPD) and has subsequently been associated to COPD and
      emphysema in several populations. We aimed to further examine the role of
      SERPINE2 polymorphisms in the development of pulmonary emphysema and different
      emphysema subtypes. METHODS: Four single nucleotide polymorphisms (SNPs) in
      SERPINE2 were analyzed from 951 clinically and radiologically examined Finnish
      construction workers. The genotype and haplotype data was compared to different
      emphysematous signs confirmed with high-resolution computed tomography (HRCT),
      forced vital capacity (FVC), forced expiratory volume in one second (FEV1),
      diffusing capacity (DLCO), and specific diffusing capacity (DLCO/VA). RESULTS:
      Three of the studied SERPINE2 SNPs (rs729631, rs975278, and rs6748795) were found
      to be in tight linkage disequilibrium. Therefore, only one of these SNPs
      (rs729631) was included in the subsequent analyses, in addition to the rs840088
      SNP which was in moderate linkage with the other three studied SNPs. The rs729631
      SNP showed a significant association with panlobular emphysema (p = 0.003). In
      further analysis, the variant allele of the rs729631 SNP was found to pose over
      two-fold risk (OR 2.22, 95% CI 1.05-4.72) for overall panlobular changes and over
      four-fold risk (OR 4.37, 95% CI 1.61-11.86) for pathological panlobular changes.
      A haplotype consisting of variant alleles of both rs729631 and rs840088 SNPs was
      found to pose an almost four-fold risk for overall panlobular (OR 3.72, 95% CI
      1.56-8.90) and subnormal (OR 3.98, 95% CI 1.55-10.20) emphysema. CONCLUSIONS: Our
      results support the previously found association between SERPINE2 polymorphisms
      and pulmonary emphysema. As a novel finding, our study suggests that the SERPINE2
      gene may in particular be involved in the development of panlobular changes,
      i.e., the same type of changes that are involved in alpha-1-antitrypsin (AAT) 
      deficiency.

PMID- 22145705
TI  - UV-B exposure causes DNA damage and changes in protein expression in northern
      pike (Esox lucius) posthatched embryos.
AB  - The ongoing anthropogenically caused ozone depletion and climate change has
      increased the amount of biologically harmful UV-B radiation, which is detrimental
      to fish in embryonal stages. The effects of UV-B radiation on the levels and
      locations of DNA damage manifested as cyclobutane pyrimidine dimers (CPDs), heat
      shock protein 70 (HSP70) and p53 protein in newly hatched embryos of pike were
      examined. Pike larvae were exposed in the laboratory to current and enhanced
      doses of UV-B radiation. UV-B exposure caused the formation of CPDs in a fluence
      rate-dependent manner, and the CPDs were found deeper in the tissues with
      increasing fluence rates. UV-B radiation induced HSP70 in epidermis, and caused
      plausible p53 activation in the brain and epidermis of some individuals. Also at
      a fluence rate occurring in nature, the DNA damage in the brain and eyes of pike
      and changes in protein expression were followed by severe behavioral disorders,
      suggesting that neural molecular changes were associated with functional
      consequences.

PMID- 22145706
TI  - Wash-free, electrochemical platform for the quantitative, multiplexed detection
      of specific antibodies.
AB  - The diagnosis, prevention, and treatment of many illnesses, including infectious
      and autoimmune diseases, would benefit from the ability to measure specific
      antibodies directly at the point of care. Thus motivated, we designed a wash
      free, electrochemical method for the rapid, quantitative detection of specific
      antibodies directly in undiluted, unprocessed blood serum. Our approach employs
      short, contiguous polypeptide epitopes coupled to the distal end of an electrode
      bound nucleic acid "scaffold" modified with a reporting methylene blue. The
      binding of the relevant antibody to the epitope reduces the efficiency with which
      the redox reporter approaches, and thus exchanges electrons with, the underlying
      sensor electrode, producing readily measurable change in current. To demonstrate
      the versatility of the approach, we fabricated a set of six such sensors, each
      aimed at the detection of a different monoclonal antibody. All six sensors are
      sensitive (subnanomolar detection limits), rapid (equilibration time constants ~8
      min), and specific (no appreciable cross reactivity with the targets of the other
      five). When deployed in a millimeter-scale, an 18-pixel array with each of the
      six sensors in triplicate support the simultaneous measurement of the
      concentrations of multiple antibodies in a single, submilliliter sample volume.
      The described sensor platform thus appears be a relatively general approach to
      the rapid and specific quantification of antibodies in clinical materials.

PMID- 22145707
TI  - Defining the role of baclofen for the treatment of alcohol dependence: a
      systematic review of the evidence.
AB  - The pharmacological properties of baclofen, a GABA(B) receptor agonist, have led
      to investigation of its use for the off-label treatment of alcohol dependence.
      Literature examining the role of baclofen in alcohol dependence suggests that it
      may be a useful medication in the treatment armamentarium with an additional
      benefit of promoting abstinence and reducing alcohol-associated cravings and
      anxiety. We conducted a systematic review of prospective, randomized controlled
      trials comparing baclofen with placebo for the treatment of alcohol dependence.
      Four randomized controlled trials were identified but only three met criteria for
      inclusion. The excluded trial was a post hoc analysis of data collected from an
      original trial whose primary outcome did not fit our inclusion criteria and was
      terminated prior to completion. Compared with placebo, subjects randomized to
      baclofen experienced higher rates of abstinence and lower anxiety scores; the
      effect of baclofen was statistically significant in two trials assessing patients
      with more severe alcohol dependence and non-significant in a trial of outpatients
      receiving concomitant manualized psychotherapy. Baclofen appeared to be safe,
      well tolerated and to have low addiction liability even in the setting of
      moderate-to-severe liver cirrhosis, a known complication of alcohol dependence.
      Though baclofen may hold promise, the different outcomes and sample populations
      of the three studies highlight the need for more research to better understand
      the appropriate target patient population to benefit from this medication.
      Questions still remain about optimal dosing and duration. There is not enough
      evidence to support the use of baclofen as a first-line treatment option, except
      for those alcohol-dependent patients with moderate-to-severe liver cirrhosis in
      whom other pharmacological treatments are not safe or practical.

PMID- 22145709
TI  - Particulate matter concentrations in residences: an intervention study evaluating
      stand-alone filters and air conditioners.
AB  - This study, a randomized controlled trial, evaluated the effectiveness of free
      standing air filters and window air conditioners (ACs) in 126 low-income
      households of children with asthma. Households were randomized into a control
      group, a group receiving a free-standing HEPA filter placed in the child's
      sleeping area, and a group receiving the filter and a window-mounted AC. Indoor
      air quality (IAQ) was monitored for week-long periods over three to four seasons.
      High concentrations of particulate matter (PM) and carbon dioxide were frequently
      seen. When IAQ was monitored, filters reduced PM levels in the child's bedroom by
      an average of 50%. Filter use varied greatly among households and declined over
      time, for example, during weeks when pollutants were monitored, filter use was
      initially high, averaging 84+/-27%, but dropped to 63+/-33% in subsequent
      seasons. In months when households were not visited, use averaged only 34+/-30%.
      Filter effectiveness did not vary in homes with central or room ACs. The study
      shows that measurements over multiple seasons are needed to characterize air
      quality and filter performance. The effectiveness of interventions using free
      standing air filters depends on occupant behavior, and strategies to ensure
      filter use should be an integral part of interventions. PRACTICAL IMPLICATIONS:
      Environmental tobacco smoke (ETS) increased particulate matter (PM) levels by
      about 14 MUg/m3 and was often detected using ETS-specific tracers despite
      restrictions on smoking in the house as reported on questionnaires administered
      to caregivers. PM concentrations depended on season, filter usage, relative
      humidity, air exchange ratios, number of children, outdoor PM levels,
      sweeping/dusting, and presence of a central air conditioner (AC). Free-standing
      air filters can be an effective intervention that provides substantial reductions
      in PM concentrations if the filters are used. However, filter use was variable
      across the study population and declined over the study duration, and thus
      strategies are needed to encourage and maintain use of filters. The variability
      in filter use suggests that exposure misclassification is a potential problem in
      intervention studies using filters. The installation of a room AC in the bedroom,
      intended to limit air exchange ratios, along with an air filter, did not lower PM
      levels more than the filter alone.

PMID- 22145710
TI  - Molecular identification of a polyM-specific alginate lyase from  Pseudomonas 
      sp. strain KS-408 for degradation of glycosidic linkages between two mannuronates
      or mannuronate and guluronate in alginate.
AB  - An alginate lyase gene of a newly isolated Pseudomonas sp. strain KS-408 was
      cloned by using PCR with the specific primers designed from homologous nucleotide
      sequences. A partial protein sequence of KS-408 alginate lyase was homology
      modeled on the basis of the crystal structure of A1-III alginate lyase from
      Sphingomonas sp. strain A1. The proposed 3-D structure of KS-408 alginate lyase
      shows that Asn-198, His-199, Arg-246, and Tyr-253 residues are conserved for the
      catalytic active site. The recombinant KS-408-1F (with signal peptide) and KS-408
      2F (without signal peptide) alginate lyases with the (His)(6) tag consist of 393
      (44.5 kDa) and 372 (42.4 kDa) amino acids with isoelectric points of 8.64 and
      8.46, respectively. The purified recombinant KS-408 alginate lyase was very
      stable when it was incubated at 40  degrees C for 30 min. Alginate
      oligosaccharides produced by the KS-408-2F alginate lyase were purified on a Bio
      Gel P2 column and analyzed by thin-layer chromatography, fast-protein liquid
      chromatography, and electrospray ionization mass spectrometry. (1)H NMR data
      showed that the KS-408-2F alginate lyase cleaved the glycosidic linkages between
      two mannuronates (mannuronate-beta(1-4)-mannuronate) or mannuronate and
      guluronate (mannuronate-beta(1-4)-guluronate), indicating that the KS-408
      alginate lyase is a polyM-specific lyase.

PMID- 22145708
TI  - GABA(A) receptor physiology and its relationship to the mechanism of action of
      the 1,5-benzodiazepine clobazam.
AB  - Clobazam was initially developed in the early 1970s as a nonsedative anxiolytic
      agent, and is currently available as adjunctive therapy for epilepsy and anxiety
      disorders in more than 100 countries. In October 2011, clobazam (OnfiTM; Lundbeck
      Inc., Deerfield, IL, USA) was approved by the US FDA for use as adjunctive
      therapy for the treatment of seizures associated with Lennox-Gastaut syndrome in
      patients aged 2 years and older. It is a long-acting 1,5-benzodiazepine whose
      structure distinguishes it from the classic 1,4-benzodiazepines, such as
      diazepam, lorazepam and clonazepam. Clobazam is well absorbed, with peak
      concentrations occurring linearly 1-4 hours after administration. Both clobazam
      and its active metabolite, N-desmethylclobazam, are metabolized in the liver via
      the cytochrome P450 pathway. The mean half-life of N-desmethylclobazam (67.5
      hours) is nearly double the mean half-life of clobazam (37.5 hours). Clobazam was
      synthesized with the anticipation that its distinct chemical structure would
      provide greater efficacy with fewer benzodiazepine-associated adverse effects.
      Frequently reported adverse effects of clobazam therapy include dizziness,
      sedation, drowsiness and ataxia. Evidence gathered from approximately 50 epilepsy
      clinical trials in adults and children indicated that the sedative effects
      observed with clobazam treatment were less severe than those reported with 1,4
      benzodiazepines. In several studies of healthy volunteers and patients with
      anxiety, clobazam appeared to enhance participants' performance in cognitive
      tests, further distinguishing it from the 1,4-benzodiazepines. The anxiolytic and
      anticonvulsant effects of clobazam are associated with allosteric activation of
      the ligand-gated GABA(A) receptor. GABA(A) receptors are found extensively
      throughout the CNS, occurring synaptically and extrasynaptically. GABA(A)
      receptors are composed of five protein subunits, two copies of a single type of
      alpha subunit, two copies of one type of beta subunit and a gamma subunit. This
      arrangement results in a diverse assortment of receptor subtypes. As
      benzodiazepine pharmacology is influenced by differences in affinity for
      particular GABA(A) subtypes, characterizing the selectivity of different
      benzodiazepines is a promising avenue for establishing appropriate use of these
      agents in neurological disorders. Molecular techniques have significantly
      advanced since the inception of clobazam as a clinical agent, adding to the
      understanding of the GABA(A) receptor, its subunits and benzodiazepine
      pharmacology. Transgenic mouse models have been particularly useful in this
      regard. Comparative studies between transgenic and wild-type mice have further
      defined relationships between GABA(A) receptor composition and drug effects. From
      such studies, we have learned that sedating and amnesic effects are mediated by
      the GABA(A) alpha(1) subunit, alpha(2) receptors mediate anxiolytic effects,
      alpha subunits are involved with anticonvulsant activity, alpha(5) may be
      implicated in learning and memory, and beta(3) subunit deficiency decreases GABA
      inhibition. Despite progress in determining the role of various subunits to
      specific benzodiazepine pharmacological actions, the precise mechanism of action
      of clobazam, and more importantly, how that mechanism of action translates into
      clinical consequences (i.e. efficacy, tolerability and safety) remain unknown.
      Testing clobazam and 1,4-benzodiazepines using a range of recombinant GABA(A)
      receptor subtypes would hopefully elucidate the subunits involved and strengthen
      our understanding of clobazam and its mechanism of action.

PMID- 22145711
TI  - Solvent free hydroxylation of the methyl esters of Blighia unijugata seed oil in
      the presence of cetyltrimethylammonium permanganate.
AB  - Extraction of oil from the seed of Blighia unijugata gave a yield of 50.82 +/-
      1.20% using hexane in a soxhlet extractor. The iodine and saponification values
      were 67.60 +/- 0.80 g iodine/100 g and 239.20 +/- 1.00 mg KOH/g respectively with
      C18:1 being the dominant fatty acid. Unsaturated methyl esters of Blighia
      unijugata which had been previously subjected to urea adduct complexation was
      used to synthesize methyl 9, 10-dihydroxyoctadecanoate via hydroxylation in the
      presence of cetyltrimethylammonium permanganate (CTAP). The reaction was
      monitored and confirmed using FTIR and GC-MS. This study has revealed that
      oxidation reaction of mono unsaturated bonds using CTAP could be achieved under
      solvent free condition.

PMID- 22145712
TI  - Psychometric properties of the Chinese version of Dermatology Life Quality Index
      (DLQI) in 851 Chinese patients with psoriasis.
AB  - BACKGROUND: The Dermatology Life Quality Index (DLQI) is one of the most
      frequently used scales to evaluate the impact of skin disease on patients'
      quality of life (QoL). There has not been psychometric evaluation of the Chinese
      version of DLQI in Chinese patients with psoriasis. OBJECTIVE: The objective of
      this study was to evaluate the psychometric properties of the Chinese version of
      DLQI. METHODS: Patients with psoriasis (>= 18 years old) visiting nine hospitals
      in various regions of China were enrolled in the study. The DLQI, Psoriasis
      Disability Index (PDI) and Health Survey Short Form (SF-36) were completed.
      Severity of psoriasis was assessed by the Psoriasis Area Severity Index (PASI).
      Reliability was estimated by internal consistency. Validity was assessed using
      known-groups comparison, convergent validity and construct validity. RESULTS: In
      all, 851 patients were included in the study. The internal consistency
      reliability of the DLQI was high (Cronbach's alpha = 0.91). Known-groups
      comparison showed that the DLQI discriminated well among patients who differed in
      age, geographical region, duration of psoriasis and the PASI score. Evidence of
      convergent validity of the DLQI was proved by high correlations with the PDI and
      four subscales of SF-36 (role-physical, bodily pain, social functioning and role
      emotional): r = 0.52-0.78. Construct validity was proved by the presence of one
      factor structure that accounted for 55.9% of the variance and fitted well into
      the unidimensional model. CONCLUSION: The Chinese version of DLQI is a reliable
      and valid measure to assess patient-reported impact of skin disease and could be
      used in QoL and health outcome studies on Chinese psoriasis patients.

PMID- 22145713
TI  - Caffeic acid inhibits acute hyperhomocysteinemia-induced leukocyte rolling and
      adhesion in mouse cerebral venules.
AB  - OBJECTIVE: To investigate the effects and possible mechanisms of CA on acute HHcy
      induced leukocyte rolling and adhesion in mouse cerebral venules. METHODS: Male
      C57 BL/6J mice were injected with DL-Hcy (50 mg/kg) and CA (10 mg/kg). The effect
      of CA on HHcy-induced leukocyte rolling and adhesion in cerebral vessels was
      assessed using intravital microscopy. Plasma cytokines and chemokines were
      evaluated by cytometric bead array. ROS production in HUVECs and adhesion
      molecule expression on leukocytes were determined by flow cytometry. E-selectin
      and ICAM-1 expression in cerebrovascular endothelium was detected by
      immunohistochemistry. CD18 phosphorylation and the Src/PI3K/Akt pathway in
      leukocytes were determined by confocal microscopy and Western blot. RESULTS: CA
      inhibited HHcy-elicited leukocyte rolling and adhesion, decreased ROS production
      in HUVECs, and reduced plasma KC, MIP-2, and MCP-1 levels. CA reduced the E
      selectin and ICAM-1 expression on cerebrovascular endothelium and CD11b/CD18 on
      leukocytes caused by HHcy. Of notice, CA depressed CD18 phosphorylation and the
      Src/PI3K/Akt pathway in leukocytes. CONCLUSIONS: CA inhibited HHcy-provoked
      leukocyte rolling and adhesion in cerebral venules, ameliorating adhesion
      molecule expression and activation, which is related to the suppression of the
      Src/PI3K/Akt pathway in leukocytes.

PMID- 22145714
TI  - Cytokines and growth factors modify the upregulation of contractile endothelin
      ET(A)  and ET(B)  receptors in rat cerebral arteries after organ culture.
AB  - AIM: Experimental cerebral ischaemia and organ culture of cerebral arteries
      induce an increased endothelin ET(B)  receptor-mediated contraction. The aim of
      this study was to examine whether cytokines and growth factors, known to be
      activated in ischaemia, can influence the expression and function of endothelin
      receptors after organ culture. METHODS: Rat middle cerebral arteries were
      cultured for 24 h at 37  degrees C in humidified 5% CO(2)  and air in culture
      medium alone, or with tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta
      (IL-1beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF)
      or basic fibroblast growth factor (bFGF). Concentration-response curves were
      obtained for sarafotoxin 6c (ET(B)  receptor agonist) and endothelin-1 (here
      ET(A)  receptor agonist, because of ET(B)  receptor desensitization). The
      receptor mRNA expression was examined by real-time PCR and the protein expression
      by immunohistochemistry and Western blot. RESULTS: Tumour necrosis factor-alpha
      (100 ng mL(-1) ) and EGF (20 ng mL(-1) ) potentiated the ET(B)  receptor-mediated
      contraction (increase in pEC(50)  without change in E(max) ). bFGF (10 ng mL(-1)
      ) and IL-1beta (10 ng mL(-1) ) induced an enhanced ET(A)  receptor-mediated
      contraction. bFGF (10 ng mL(-1) ) significantly increased the ET(B)  mRNA level,
      and EGF (20 ng mL(-1) ) increased the ET(A)  receptor protein. Increased ET(B) 
      receptor mRNA and protein level also were observed after treatment with IL-1beta
      (10 ng mL(-1) ). CONCLUSION: This study shows that TNF-alpha, IL-1beta, EGF and
      bFGF can modify the expression and function of endothelin receptors during organ
      culture. Because there is similar receptor upregulation in experimental stroke,
      the effect of cytokines and growth factors on endothelin receptor upregulation is
      an interesting aspect to study in vivo.

PMID- 22145715
TI  - Surfactant-based dispersant for multiwall carbon nanotubes to prepare ceramic
      composites by a sol-gel method.
AB  - A dispersant for multiwall carbon nanotubes (MWCNTs) is proposed that fulfils the
      requirements of creating a uniform dispersion in the matrix and obtaining a good
      interface between CNTs and the matrix, and is soluble in generic nonpolar
      solvents. This dispersant is based on a long chain surfactant, called in this
      work dabcosil stearate, containing a stearate-based 18-carbon alkyl chain as an
      anion, and a silsesquioxane containing a bridged, positively charged 1,4
      diazoniabicyclo[2.2.2]octane group. It provides not only a very good dispersion
      medium for the MWCNTs, but also a very good interface between MWCNTs and ceramic
      matrices, such as alumina and zirconia, prepared by the sol-gel method.

PMID- 22145716
TI  - Learning from and teaching the next generation.

PMID- 22145717
TI  - Welcoming Jay Lebow, Ph.D.: incoming editor of Family Process.

PMID- 22145718
TI  - Providing therapy to children and families in foster care: a systemic-relational
      approach.
AB  - Foster care is a system created to protect children from an unsafe home
      environment yet multiple foster home placements, conflictual or nonexistent
      relationships between foster parents and birth parents, long, drawn out court
      battles, and living in an on-going state of not knowing when or if they will be
      going home are just some of the challenges many children in care are expected to
      manage. This paper presents a guide for therapists working with families involved
      in foster care. Utilizing ideas from the postmodern therapies and structural
      family therapy, suggestions will be provided about who needs to talk to whom
      about what, when to have these necessary conversations, and how to talk to people
      in a way that mobilizes adults to take action for the children, with the goal of
      minimizing postplacement trauma, strengthening and repairing relational bonds,
      and moving children out of foster care and into permanent homes as quickly as
      possible.

PMID- 22145719
TI  - Between pink and blue: a multi-dimensional family approach to gender
      nonconforming children and their families.
AB  - Families of gender nonconforming children need to negotiate the interactions
      between two gender systems: a rigid gender binary imported from familial, social,
      and cultural experiences and a fluid gender spectrum articulated by their child.
      This article reviews parental reactions to nonconforming gender developments and
      poses that the parental mandates of protection and acceptance are problematized
      by the difference of gender norms between the child and the family, as well as
      the child and the environment. Through multiple therapeutic modalities-parental
      coaching and education, parent support group, and child and family therapy-the
      author illustrates interventions supporting both parents and prepubescent
      children in their negotiation of safety, connection, and fluidity. Case vignettes
      illustrate the method in action.

PMID- 22145720
TI  - The marriage checkup: increasing access to marital health care.
AB  - Despite the ongoing prevalence of marital distress, very few couples seek
      therapy. Researchers and clinicians have increasingly been calling for innovative
      interventions that can reach a larger number of untreated couples. Based on a
      motivational marital health model, the Marriage Checkup (MC) was designed to
      attract couples who are unlikely to seek traditional tertiary therapy. The
      objective of the MC is to promote marital health for as broad a population of
      couples as possible, much like regular physical health checkups. This first paper
      from the largest MC study to date examines whether the MC engaged previously
      unreached couples who might benefit from intervention. Interview and survey data
      suggested that the MC attracted couples across the distress continuum and was
      perceived by couples as more accessible than traditional therapy. Notably, the MC
      attracted a substantial number of couples who had not previously participated in
      marital interventions. The motivational health checkup model appeared to
      encourage a broad range of couples who might not have otherwise sought
      relationship services to deliberately take care of their marital health. Clinical
      implications are discussed.

PMID- 22145721
TI  - A participatory approach to healing and transformation in South Africa.
AB  - In this article I describe my personal journey from working as private
      practitioner to participating in the wider South African society. Post-apartheid
      South African society struggles with overwhelming problems related to poverty,
      illness, violence, sexism, and racism. Moreover, in those communities where the
      trauma is most severe, professional resources are scarce. I propose a
      participatory approach which invites therapists to respond to these socio
      economic and political challenges and the problems that arise from them by
      thinking and acting outside the constraints of their consultation rooms and of
      traditional therapeutic conversations, into active participation in ways that
      might support healing and social transformation. I use two examples to illustrate
      and discuss the participatory approach with which I have engaged for over 10
      years. The illustrative examples show how a participatory approach can create
      ripples that impact communities in healing and transformative ways.

PMID- 22145722
TI  - Exposing operations of power in supervisory relationships.
AB  - Through a poststructural lens, we examine how power may show itself in
      relationships between supervisees and supervisors, producing both helpful and
      harmful effects. Drawing from our own experiences, as well as conversations with
      other members of our supervisory group, we demonstrate how privileged discourses
      around professional status, gender, and race may bring about difficulties
      including a sense of doubt, worry, inadequacy, and a fear of speaking up. We also
      illustrate how these difficulties can be addressed in a manner that may lessen
      their influence, while increasing supervisees' sense of agency.

PMID- 22145723
TI  - A socio-emotional relational framework for infidelity: the relational justice
      approach.
AB  - Current clinical models for addressing infidelity tend not to make social context
      issues a central focus; yet, societal gender and power structures, such as female
      responsibility for relationships and limited male vulnerability, affect the
      etiology of affairs and create power imbalances in intimate relationships. How
      therapists respond to these societal influences may either limit or enhance the
      mutual healing of both persons in the relationship. Thus attention to these
      societal processes is an ethical issue. This paper presents one perspective, the
      Relational Justice Approach, for working with infidelity. It places gender,
      power, and culture at the center of intervention in couple therapy, and includes
      three stages: (1) creating an equitable foundation for healing, (2) placing the
      infidelity in a societal context, and (3) practicing mutuality. Each stage is
      illustrated with case examples and contrasted with current practice regarding
      infidelity.

PMID- 22145724
TI  - Collaborative helping maps: a tool to guide thinking and action in family
      centered services.
AB  - This article highlights "disciplined improvisation" as a metaphor for community
      based work with multi-stressed families. It introduces Collaborative Helping maps
      as a tool that both helps workers think their way through complex situations with
      families and provides a structure to support constructive conversations between
      workers and families about challenging situations. The article illustrates this
      map through a clinical vignette and uses interviews with workers to highlight
      ways in which the map can both enhance worker thinking and support constructive
      conversations between workers and families about problems that could easily
      divide them and lead to polarization and escalating tension.

PMID- 22145725
TI  - Developing an outcome-based assessment for family therapy training: the Rochester
      Objective Structured Clinical Evaluation (ROSCE).
AB  - This paper addresses a growing need for cost-effective, outcome-based assessment
      in family therapy training. We describe the ROSCE, a structured, evidence
      informed, learner-centered approach to the assessment of clinical skills
      developed at the University of Rochester Medical Center. The ROSCE emphasizes
      direct observation of trainees demonstrating clinical competencies. The format
      integrates both formative and summative assessment methods. It can readily be
      adapted to a wide variety of educational and training settings.

PMID- 22145726
TI  - Insider knowledge.

PMID- 22145731
TI  - Clitoral neuroma after female genital mutilation/cutting: a rare but possible
      event.
AB  - INTRODUCTION: Female genital mutilation/cutting (FGM/C), in particular, type III,
      also called infibulation, can cause various long-term complications. However,
      posttraumatic neuroma of the clitoris is extremely rare; only one case was
      previously reported in the literature. AIM: The aim of this study was to describe
      the case of a patient presenting a clitoral neuroma post-FGM/C in detail and her
      successful multidisciplinary treatment. METHODS: We report the case of a 24-year
      old woman originating from Somalia presenting a type III a-b FGM/C who attended
      our outpatient clinic at the Geneva University Hospitals complaining of primary
      dysmenorrhea and a post-mutilation painful clitoral mass. The mass was clinically
      diagnosed as a cyst and surgically removed. Histopathological analysis revealed
      that it was a posttraumatic neuroma and a foreign body granuloma around the
      ancient surgical thread. Our patient was also offered a multidisciplinary
      counseling by a specialized gynecologist on FGM/C, a sexologist, and a
      reproductive and sexual health counselor. RESULTS: One month after surgical
      treatment, the vulvar pain was over. CONCLUSIONS: This is the second case of
      clitoral neuroma after FGM/C reported and the first with complete clinical, as
      well as histopathological documentation and multidisciplinary care. Considering
      the high frequency of clitoral cysts in case of infibulation, clitoral neuroma
      should be considered in the differential diagnosis. In this case, if symptomatic,
      the treatment should be surgery, clinical follow-up, and counseling. If
      necessary, appropriate sexual therapy should be offered too.

PMID- 22145732
TI  - Computational model-based design of a wearable artificial pump-lung for
      cardiopulmonary/respiratory support.
AB  - Mechanical ventilation and extracorporeal membrane oxygenation are the only
      immediate options available for patients with respiratory failure. However, these
      options present significant shortcomings. To address this unmet need for
      respiratory support, innovative respiratory assist devices are being developed.
      In this study, we present the computational model-based design, and analysis of
      functional characteristics and hemocompatibility performance, of an innovative
      wearable artificial pump-lung (APL) for ambulatory respiratory support. Computer
      aided design and computational fluid dynamics (CFD)-based modeling were utilized
      to generate the geometrical model and to acquire the fluid flow field, gas
      transfer, and blood damage potential. With the knowledge of flow field, gas
      transfer, and blood damage potential through the whole device, design parameters
      were adjusted to achieve the desired specifications based on the concept of
      virtual prototyping using the computational modeling in conjunction with
      consideration of the constraints on fabrication processes and materials. Based on
      the results of the CFD design and analysis, the physical model of the wearable
      APL was fabricated. Computationally predicted hydrodynamic pumping function, gas
      transfer, and blood damage potential were compared with experimental data from in
      vitro evaluation of the wearable APL. The hydrodynamic performance, oxygen
      transfer, and blood damage potential predicted with computational modeling, along
      with the in vitro experimental data, indicated that this APL meets the design
      specifications for respiratory support with excellent biocompatibility at the
      targeted operating condition.

PMID- 22145733
TI  - Surgical reconstruction of peri-implant bone defects with prehydrated and
      collagenated porcine bone and collagen barriers: case presentations.
AB  - BACKGROUND: Surgical reconstruction of peri-implant defects is challenging and
      unpredictable due to, for example, the extent of the bone defect or the
      osteogenic potential of adjunctive materials used. PURPOSE: To study the healing
      capacity of a new bone xenograft material in the treatment of peri-implant
      defects. MATERIAL AND METHODS: In three cases with advanced peri-implant defects,
      flap surgery was performed. After thorough debridement including cleaning of the
      exposed implant surface, prehydrated and collagenated porcine bone (PCPB)
      particles were placed into the defect. A bioresorbable collagen barrier was
      adapted and placed over the defect and the flaps were relocated. After 6 and 12
      months of healing, clinical and radiographic examinations were done. In one case,
      the surgical procedure was repeated 6 months postoperatively. One year after the
      second surgery, a bone biopsy was harvested and analyzed with histology. RESULTS:
      All defects healed uneventfully. At 6 months, probing depths were reduced by 3-4
      mm with no bleeding on probing or pus formation. At 12 months, healthy peri
      implant conditions were found. Intra-oral radiographs showed gain of the marginal
      bone level by 2-4 mm. In the case where reconstructive surgery was repeated,
      histology showed osteoconductive properties as bone formation with typical
      osteoblastic seams was observed directly on the surface of the grafted particles.
      CONCLUSION: The presented cases show that PCPB have favorable properties
      enhancing bone regeneration in peri-implant bone defects.

PMID- 22145734
TI  - Positive effects of subclinical depression in prospective memory and ongoing
      tasks in young and old adults.
AB  - Results reported in the literature show that depression can have either negative
      or neutral effects on prospective memory (PM). The goal of the present study was
      to broaden the analysis of depression-related effects on PM, with regard to the
      possibility that subclinical depression may have positive influence on PM. A
      total of 120 participants from four groups (young/old, subclinically
      depressed/non-depressed) completed event- and time-based PM tasks embedded in the
      linear orders task or stories task, respectively. In the event-based PM task no
      effects of depression were found, whereas depressed participants were more
      accurate in the time-based PM task, where higher monitoring during the last
      minute of the task was observed. It was also found that depressed participants
      built a mental model in the linear orders task more accurately than controls.
      Results of the present study are discussed with reference to the analytical
      rumination hypothesis.

PMID- 22145735
TI  - Manganese K-edge X-ray absorption spectroscopy as a probe of the metal-ligand
      interactions in coordination compounds.
AB  - A series of manganese coordination compounds has been investigated by X-ray
      absorption spectroscopy (XAS). The K-pre-edge spectra are interpreted with the
      aid of time-dependent density functional theory (TD-DFT). This method was
      calibrated for the prediction of manganese K-pre-edges with different
      functionals. Moreover the nature of all observed features could be identified and
      classified according to the corresponding set of acceptor orbitals, either 1s to
      3d transitions or metal-to-ligand charge transfer (MLCT) bands. The observable
      MLCT bands are further divided into features that correspond to transitions into
      empty pi* orbitals of pi-donor ligands and those of pi-acceptor ligands. The
      ability to computationally reproduce the observed features at the correct
      relative transition energy is strongly dependent on the nature of the transition.
      A detailed analysis of the electronic structure of a series of Mn coordination
      compounds reveals that the different classes of observable transitions provide
      added insight into metal-ligand bonding interactions.

PMID- 22145736
TI  - Dithiocarbamates strongly inhibit the beta-class carbonic anhydrases from
      Mycobacterium tuberculosis.
AB  - A series of N-mono- and N,N-disubstituted dithiocarbamates have been investigated
      as inhibitors of two beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the
      bacterial pathogen Mycobacterium tuberculosis, mtCA 1 (Rv1284) and mtCA 3
      (Rv3273). Both enzymes were inhibited with efficacies between the subnanomolar to
      the micromolar one, depending on the substitution pattern at the nitrogen atom
      from the dithiocarbamate zinc-binding group. Aryl, arylalkyl-, heterocyclic as
      well as aliphatic and amino acyl such moieties led to potent mtCA 1 and 3
      inhibitors in both the N-mono- and N,N-disubstituted dithiocarbamate series. This
      new class of beta-CA inhibitors may have the potential for developing
      antimycobacterial agents with a diverse mechanism of action compared to the
      clinically used drugs for which many strains exhibit multi-drug/extensive multi
      drug resistance.

PMID- 22145737
TI  - Dysplasia in the ileal pouch revisited: what does it mean and what does it imply?

PMID- 22145739
TI  - Salvage colectomy for endoscopically removed malignant colon polyps: is it
      possible to determine the optimal number of lymph nodes that need to be
      harvested?
AB  - AIM: The total number of lymph nodes examined after salvage colectomy for
      endoscopically removed malignant polyps was evaluated and an attempt was made to
      determine whether there was an optimal number of lymph nodes that should be
      harvested. METHOD: From 2000 to 2009, 531 patients underwent segmental resection
      for non-metastatic colon cancer. Of these, 22 underwent a salvage colectomy for
      an endoscopically removed malignant polyp, the main indication for which was a
      resection margin of < 1 mm. The surgical procedure was identical to that used for
      all colon cancers. RESULTS: The mean number of lymph nodes examined was 11.6 +/-
      7.6 for the 22 patients with an endoscopically removed malignant polyp and 26.2
      +/- 13.9 for the remaining 509 patients (P = 0.0006). Fewer than 12 lymph nodes
      were examined in 62 (12%) of the 509 patients and in 13 (59%) of the 22 patients
      with an endoscopically removed malignant polyp (P < 0.0001). In the group of 22
      patients who underwent a salvage colectomy, the total number of lymph nodes
      examined ranged from 2 to 33. At a mean follow up of 41 +/- 15.6 months, no local
      or distant recurrence was observed in the 22 patients. CONCLUSION: The total
      number of lymph nodes examined after colectomy for endoscopically removed
      malignant polyps varies and is less than the recommended number of 12 in most
      cases: this does not appear to have long-term prognostic significance. There is
      no biological reason to explain this clinical observation.

PMID- 22145740
TI  - The consequences of good clinical practice for investigator-initiated research.

PMID- 22145743
TI  - Factors influencing oral hygiene behaviour and gingival outcomes 3 and 12 months
      after initial periodontal treatment: an exploratory test of an extended Theory of
      Reasoned Action.
AB  - AIM: The aim was to empirically test the extended Theory of Reasoned Action (TRA)
      and the prospective direct and indirect role of attitudes, beliefs, subjective
      norms, self-efficacy, and a cognitive behavioural intervention in adult's oral
      hygiene behaviour and gingival outcomes at 3- and 12-month follow-up. MATERIALS
      AND METHODS: Data were derived from an RCT evaluating the effectiveness of oral
      hygiene educational programs integrated in non-surgical periodontal treatment (n
      = 113). Before baseline examination, participants completed a self-report
      questionnaire. Structural equation modelling using maximum likelihood estimation
      with bootstrapping was used to test the direct and indirect (mediated) pathways
      within the extended TRA model. RESULTS: The extended TRA model explained a large
      amount of variance in gingival outcome scores at 12 months (56%). A higher level
      of self-efficacy at baseline was associated with higher frequencies of oral
      hygiene behaviour at 3 months. Being female was linked to more normative beliefs
      that, in turn, related to greater behavioural beliefs and self-efficacy. Gender
      was also related to behavioural beliefs, attitudes and subjective norms. Both
      frequency of oral hygiene behaviour at 3 months and the cognitive behavioural
      intervention predicted gingival outcome at 12 months. CONCLUSIONS: The model
      demonstrated that self-efficacy, gender and a cognitive behavioural intervention
      were important predictors of oral hygiene behavioural change.

PMID- 22145744
TI  - Effects of Lactobacillus rhamnosus GG supplementation on cow's milk allergy in a
      mouse model.
AB  - BACKGROUND: Cow's milk allergy (CMA) is one of the most prevalent human food
      borne allergies, particularly in infants and young children from developed
      countries. Our study aims to evaluate the effects of Lactobacillus rhamnosus GG
      (LGG) administration on CMA development using whole cow's milk proteins (CMP)
      sensitized Balb/C mice by two different sensitization methods. METHODS: LGG
      supplemented mice were either sensitized orally with CMP and cholera toxin B
      subunit (CTB) as adjuvant, or intraperitoneally (IP) with CMP but without the
      adjuvant. Mice were then orally challenged with CMP and allergic responses were
      accessed by monitoring hypersensitivity scores, measuring the levels of CMP
      specific immunoglobulins (IgG1, IgG2a and IgG) and total IgE from sera, and
      cytokines (IL-4 and IFN-gamma) from spleen lysates. RESULTS: Sensitization to CMP
      was successful only in IP sensitized mice, but not in orally sensitized mice with
      CMP and CTB. Interestingly, LGG supplementation appeared to have reduced cow's
      milk allergy (CMA) in the IP group of mice, as indicated by lowered allergic
      responses. CONCLUSIONS: Adjuvant-free IP sensitization with CMP was successful in
      inducing CMA in the Balb/C mice model. LGG supplementation favourably modulated
      immune reactions by shifting Th2-dominated trends toward Th1-dominated responses
      in CMP sensitized mice. Our results also suggest that oral sensitization by the
      co-administration of CMP and CTB, as adjuvant, might not be appropriate to induce
      CMA in mice.

PMID- 22145745
TI  - Solution and solid-state effects on NMR chemical shifts in sesquiterpene
      lactones: NMR, X-ray, and theoretical methods.
AB  - Selected guaianolide type sesquiterpene lactones were studied combining solution
      and solid-state NMR spectroscopy with theoretical calculations of the chemical
      shifts in both environments and with the X-ray data. The experimental (1)H and
      (13)C chemical shifts in solution were successfully reproduced by theoretical
      calculations (with the GIAO method and DFT B3LYP 6-31++G**) after geometry
      optimization (DFT B3LYP 6-31 G**) in vacuum. The GIPAW method was used for
      calculations of solid-state (13)C chemical shifts. The studied cases involved two
      polymorphs of helenalin, two pseudopolymorphs of 6alpha-hydroxydihydro-aromaticin
      and two cases of multiple asymmetric units in crystals: one in which the symmetry
      independent molecules were connected by a series of hydrogen bonds (geigerinin)
      and the other in which the symmetry-independent molecules, deprived of any
      specific intermolecular interactions, differed in the conformation of the side
      chain (badkhysin). Geometrically different molecules present in the crystal
      lattices could be easily distinguished in the solid-state NMR spectra. Moreover,
      the experimental differences in the (13)C chemical shifts corresponding to nuclei
      in different polymorphs or in geometrically different molecules were nicely
      reproduced with the GIPAW calculations.

PMID- 22145746
TI  - Cortical injury in multiple sclerosis; the role of the immune system.
AB  - The easily identifiable, ubiquitous demyelination and neuronal damage that occurs
      within the cerebral white matter of patients with multiple sclerosis (MS) has
      been the subject of extensive study. Accordingly, MS has historically been
      described as a disease of the white matter. Recently, the cerebral cortex (gray
      matter) of patients with MS has been recognized as an additional and major site
      of disease pathogenesis. This acknowledgement of cortical tissue damage is due,
      in part, to more powerful MRI that allows detection of such injury and to focused
      neuropathology-based investigations. Cortical tissue damage has been associated
      with inflammation that is less pronounced to that which is associated with damage
      in the white matter. There is, however, emerging evidence that suggests cortical
      damage can be closely associated with robust inflammation not only in the
      parenchyma, but also in the neighboring meninges. This manuscript will highlight
      the current knowledge of inflammation associated with cortical tissue injury.
      Historical literature along with contemporary work that focuses on both the
      absence and presence of inflammation in the cerebral cortex and in the cerebral
      meninges will be reviewed.

PMID- 22145747
TI  - Collagen three-dimensional hydrogel matrix carrying basic fibroblast growth
      factor for the cultivation of mesenchymal stem cells and osteogenic
      differentiation.
AB  - Three-dimensional (3D) collagen hydrogels have been extensively used for cell
      culture experiments and are more closely representative of in vivo conditions
      than monolayer (2D) culture. Here we cultured rat bone marrow-derived mesenchymal
      stem cells (MSCs) in collagen hydrogels containing varying concentrations of
      basic fibroblast growth factor (bFGF) to examine the effect of bFGF on MSC
      proliferation and osteogenic differentiation in 3D culture. The optimal bFGF
      concentration that promoted the greatest degree of cell proliferation and
      expression of the early osteogenic induction marker alkaline phosphatase was also
      determined. Subsequent quantitative real-time polymerase chain reaction analysis
      of gene expression demonstrated that bFGF promoted significant upregulation of
      the bone-related genes: collagen type I, osteopontin (OPN), bone sialoprotein
      (BSP), and osteocalcin (OCN) for periods of up to 21 days. Immunofluorescence
      staining and fluorescence-activated cell sorting analysis further supported the
      enhanced osteogenic differentiation of cells as a greater proportion of cells
      were found to express OPN. Matrix mineralization within the collagen hydrogels
      was enhanced in the presence of bFGF, as assessed by calcium detection using von
      Kossa staining. These results clearly demonstrate a positive effect of bFGF on
      proliferation and osteogenic induction of MSCs in 3D collagen hydrogels when
      applied at the appropriate concentration. Moreover, collagen hydrogel constructs
      containing MSCs and appropriate growth factor stimulus might be a potentially
      useful biological tool for 3D bone tissue engineering.

PMID- 22145748
TI  - Selective permeation of moisture and VOCs through polymer membranes used in total
      heat exchangers for indoor air ventilation.
AB  - Fresh air ventilation is central to indoor environmental control. Total heat
      exchangers can be key equipment for energy conservation in ventilation. Membranes
      have been used for total heat exchangers for more than a decade. Much effort has
      been spent to achieve water vapor permeability of various membranes; however,
      relatively little attention has been paid to the selectivity of moisture compared
      with volatile organic compounds (VOCs) through such membranes. In this
      investigation, the most commonly used membranes, both hydrophilic and hydrophobic
      ones, are tested for their permeability for moisture and five VOCs (acetic acid,
      formaldehyde, acetaldehyde, toluene, and ethane). The selectivity of moisture vs.
      VOCs in these membranes is then evaluated. With a solution-diffusion model, the
      solubility and diffusivity of moisture and VOCs in these membranes are
      calculated. The resulting data could provide some reference for future material
      selection. PRACTICAL IMPLICATIONS: Total heat exchangers are important equipment
      for fresh air ventilation with energy conservation. However, their implications
      for indoor air quality in terms of volatile organic compound permeation have not
      been known. The data in this article help us to clarify the impacts on indoor VOC
      levels of membrane-based heat exchangers. Guidelines for material selection can
      be obtained for future use total heat exchangers for building ventilation.

PMID- 22145749
TI  - Incidence of toxic epidermal necrolysis and Stevens-Johnson Syndrome in an HIV
      cohort: an observational, retrospective case series study.
AB  - BACKGROUND: The incidence of Stevens-Johnson syndrome (SJS) and toxic epidermal
      necrolysis (TEN) has been reported to be between 0.95 and 1 per 1000 individuals
      with AIDS. Accessibility to a cohort of individuals with HIV with known drug
      exposure (including drug, dose, and time of exposure) and collection of adverse
      event information may provide an opportunity to determine an incidence rate of
      SJS and TEN. OBJECTIVE: The primary objective of this analysis was to determine
      the incidence of confirmed SJS and TEN in a cohort of Canadian HIV patients who
      were receiving HIV and HIV-related medications. STUDY DESIGN: This was a
      retrospective analysis of an HIV cohort. PATIENT POPULATION: The Ontario HIV
      Treatment Network (OHTN) cohort population was eligible for this analysis.
      METHODS: A search of the OHTN database was conducted to determine whether cases
      with a diagnosis of SJS or TEN were included. Search terms included 'TEN,' 'SJS,'
      'epidermal necrolysis,' and 'erythema multiforme.' All SJS and TEN cases recorded
      in the OHTN database between January 1995 and August 2008 were obtained.
      Diagnostic criteria for SJS and TEN were established and two reviewers examined
      the medical records to confirm the SJS or TEN diagnosis. Drug exposure and
      utilization were documented. Incidence rates for the entire cohort were
      calculated. RESULTS: Seventeen cases over seven OHTN study sites were identified
      from an approximate cohort sample size of 3700. There were 15 men (88%). The mean
      +/- SD age was 51.6 +/- 11.3 years and time since HIV diagnosis was 16.1 +/- 4.4
      years. Only one patient reported experiencing a previous SJS or TEN episode. Of
      the 17 cases, clinical experts diagnosed five cases as true SJS and/or TEN, two
      cases were labeled as indeterminant, and the remaining cases were considered not
      SJS or TEN. Among the confirmed cases, drugs taken included nevirapine,
      trimethoprim/sulfamethoxazole (cotrimoxazole), stavudine (d4T), and
      clarithromycin. CONCLUSIONS: The incidence of SJS and/or TEN was 5-7 per 3710 or
      approximately 1-2 per 1000 individuals in this cohort with HIV. Careful diagnosis
      of this adverse event is required for an accurate measure of incidence and to
      avoid false inflation of the incidence.

PMID- 22145750
TI  - Proteasome inhibitor bortezomib overcomes P-gp-mediated multidrug resistance in
      resistant leukemic cell lines.
AB  - INTRODUCTION: To study the effect of bortezomib alone or in combination with
      daunorubicin (DNR) on an mdr1 single-factor drug-resistant leukemia cell line
      K562/MDR1, a multifactor-resistant cell line K562/A02, a drug-sensitive cell line
      K562, and primary cells from acute myeloid leukemia patients. METHODS: The cell
      lines were exposed to bortezomib, DNR, and bortezomib plus DNR, and cell
      proliferation, cell cycle, apoptosis rate, and expression of MDR1/BCL2 were
      analyzed. RESULTS: Bortezomib potently inhibited growth and increased the
      apoptosis rate in the cell lines. In K562/MDR1 and K562/A02, the calcium channel
      blocker verapamil reduced the 50% inhibitory concentration and apoptosis rate of
      DNR, a P-gp protein substrate, but not of bortezomib. Bortezomib plus DNR had
      synergistic effect on antiproliferation (synergistic ratio > 1). Apoptosis was
      substantially more increased by the combination of two drugs than by bortezomib
      alone. Bortezomib arrested the cell cycles of three cell lines at the G2/M stage,
      decreased BCL2 mRNA expression, but did not affect MDR1 mRNA levels. The
      antiproliferative role of bortezomib was also confirmed in primary leukemia
      cells. CONCLUSION: Bortezomib is a promising potential therapy for acute
      leukemia, especially mdr1 drug-resistant leukemia.

PMID- 22145751
TI  - Redox-controlled interconversion between trigonal prismatic and octahedral
      geometries in a monodithiolene tetracarbonyl complex of tungsten.
AB  - The tetracarbonyl compounds [W(mdt)(CO)(4)] (1) and [W(Me(2)pipdt)(CO)(4)] (2)
      both have dithiolene-type ligands (mdt(2-) = 1,2-dimethyl-1,2-dithiolate;
      Me(2)pipdt = 1,4-dimethylpiperazine-2,3-dithione) but different geometries,
      trigonal prismatic (TP) and octahedral, respectively. Structural data suggest an
      ene-1,2-dithiolate ligand description, hence a divalent tungsten ion, for 1 and a
      dithioketone ligand, hence W(0) oxidation state, for 2. Density functional theory
      (DFT) calculations on 1 show the highest occupied molecular orbital (HOMO) to be
      a strong W-dithiolene pi bonding interaction and the lowest unoccupied molecular
      orbital (LUMO) its antibonding counterpart. The TP geometry is preferred because
      symmetry allowed mixing of these orbitals via a configuration interaction (CI)
      stabilizes this geometry over an octahedron. The TP geometry for 2 is disfavored
      because W-dithiolene pi overlap is attenuated because of a lowering of the sulfur
      content and a raising of the energy of this ligand pi orbital by the conjugated
      piperazine nitrogen atoms in the Me(2)pipdt ligand. A survey of the Cambridge
      Structural Database identifies other W(CO)(4) compounds with pseudo C(4v)
      disposition of CO ligands and suggests a d(4) electron count to be a probable
      common denominator. Reduction of 1 induces a geometry change to octahedral
      because the singly occupied molecular orbital (SOMO) is at lower energy in this
      geometry. The cyclic voltammogram of 1 in CH(2)Cl(2) reveals a reduction wave at 
      1.14 V (vs Fc(+)/Fc) with an unusual offset between the cathodic and the anodic
      peaks (DeltaE(p)) of 0.130 V, which is followed by a second, reversible reduction
      wave at -1.36 V with DeltaE(p) = 0.091 V. The larger DeltaE(p) observed for the
      first reduction is evidence of the trigonal prism-to-octahedron geometry change
      attending this process. Tungsten L(1)-edge X-ray absorption (XAS) data indicate a
      higher metal oxidation state in 1 than 2. Electron paramagnetic resonance data
      for [1](-) and [2](-) are both diagnostic of dithiolene ligand-based sulfur
      radical, indicating that one-electron reduction of 1 involves two-electron
      reduction of tungsten and one-electron oxidation of dithiolene ligand.

PMID- 22145757
TI  - Clay-based colloidosomes.
AB  - Poly(ethylene imine) (PEI) has been adsorbed onto the surface of Laponite clay
      nanoparticles from aqueous solution at pH 9 in order to produce an efficient
      hybrid Pickering emulsifier. This facile protocol allows formation of stable
      sunflower oil-in-water Pickering emulsions via homogenization at 12,000 rpm for 2
      min at 20  degrees C. The effect of varying the extent of PEI adsorption on the
      Pickering emulsifier performance of the surface-modified Laponite is investigated
      for five oils of varying polarity using aqueous electrophoresis,
      thermogravimetric analysis, and laser diffraction studies. A minimum volume
      average emulsion droplet diameter of around 60 MUm was achieved at a Laponite
      concentration of 0.50% by mass when utilizing a PEI/Laponite mass ratio of 0.50.
      Such emulsions proved to be very stable toward droplet coalescence over time
      scales of months, although creaming is observed on standing within days due to
      the relatively large droplet size. These conditions correspond to submonolayer
      coverage of the Laponite particles by the PEI, which ensures that there is little
      or no excess PEI remaining in the aqueous continuous phase. This situation is
      confirmed by visual inspection of the underlying aqueous phase of the creamed
      emulsion when using fluorescently labeled PEI. These Pickering emulsions are
      readily converted into novel clay-based colloidosomes via reaction of the primary
      and/or secondary amine groups on the PEI chains adsorbed at the Laponite surface
      with either oil-soluble poly(propylene glycol) diglycidyl ether or water-soluble
      poly(ethylene glycol) diglycidyl ether cross-linkers. These colloidosomes were
      sufficiently robust to survive the removal of the internal oil phase after
      washing with excess alcohol, as judged by both optical and fluorescence
      microscopy. However, dye release studies conducted with clay-based colloidosomes
      suggest that these microcapsules are highly permeable and hence do not provide an
      effective barrier for retarding the release of small molecules.

PMID- 22145758
TI  - Endograft-preserving therapy of a patient with Coxiella burnetii-infected
      abdominal aortic aneurysm: a case report.
AB  - INTRODUCTION: Coxiella burnetii, the causative agent of Q fever, may cause
      endocarditis and vascular infections that result in severe morbidity and
      mortality. We report a case of a C. burnetii-infected abdominal aorta and its
      management in a patient with a previous endovascular aortic aneurysm repair. CASE
      PRESENTATION: A 62-year-old Caucasian man was admitted to our hospital three
      months after endovascular aortic aneurysm repair with a bifurcated stent graft.
      He had increasing abdominal complaints and general malaise. A computed tomography
      scan of his abdomen revealed several para-aneurysmal abscesses. Surgery was
      performed via midline laparotomy. The entire abdominal wall of his aneurysmal
      sac, including the abscesses, was removed. The vascular endoprosthesis showed no
      macroscopic signs of infection. The decision was made to leave the endograft in
      place because of the severe cardiopulmonary comorbidities, thereby avoiding
      suprarenal clamping and explantation of this device with venous reconstruction.
      The proximal and distal parts of the endograft were secured to the aortic wall
      and common iliac artery walls, respectively, to avoid future migration.
      Polymerase chain reaction for C. burnetii was positive in all specimens of aortic
      tissue. Specific antibiotic therapy was initiated. Our patient was discharged in
      good clinical condition after six days. CONCLUSIONS: In our patient, the
      infection was limited to the abdominal aneurysm wall, which was removed, leaving
      the endograft in place. Vascular surgeons should be familiar with this bailout
      procedure in high-risk patients.

PMID- 22145759
TI  - The medical-industrial complex, professional medical associations, and continuing
      medical education.
AB  - Financial relationships among the biomedical industries, physicians, and
      professional medical associations (PMAs) can be professional, ethical, mutually
      beneficial, and, most importantly, can lead to improved medical care. However,
      such relationships, by their very nature, present conflicts of interest (COIs).
      One of the greatest concerns regarding COI is continuing medical education (CME),
      especially because currently industry funds 40-60% of CME. COIs have the
      potential to bias physicians in practice, educators, and those in leadership
      positions of PMAs and well as the staff of a PMA. These conflicts lead to the
      potential to bias the content and type of CME presentations and thereby influence
      physicians' practice patterns and patient care. Physicians are generally aware of
      the potential for bias when industry contributes funding for CME, but they are
      most often unable to detect the bias. This may because it is very subtle and/or
      the educators themselves may not realize that they have been influenced by their
      relationships with industry. Following Accreditation Council for Continuing
      Medical Education guidelines and mandating disclosure that is transparent and
      complete have become the fallback positions to manage COIs, but such disclosure
      does not really mitigate the conflict. The eventual and best solutions to ensure
      evidence-based education are complete divestment by educators and leaders of
      PMAs, minimal and highly controlled industry funding of PMAs, blind pooling of
      any industry contributions to PMAs and CME, strict verification of disclosures,
      clear separation of marketing from education at CME events, and strict oversight
      of presentations for the presence of bias.

PMID- 22145760
TI  - Characterization of bacteriophages with a lytic effect on various  Salmonella 
      serotypes and  Escherichia coli  O157:H7.
AB  - Four phages isolated from cattle and poultry feces were analyzed for their
      ability to lyse Salmonella serotypes and Escherichia coli O157:H7. The phage one
      step growth curves, morphology, and genetic characteristics were determined. All
      phages showed a lytic effect on various Salmonella serotypes and E. coli O157:H7,
      which lysed at least 70% of the 234 strains tested. The phages had latent periods
      ranging from 10 to 15 min and generation times of 30 to 45 min, while burst size
      fluctuated between 154 and 426 PFU/cell. Phages morphology showed isometric and
      elongated heads and rigid contractile tails, consistent with morphology of the
      Myoviridae family. Phages' DNA dendrograms showed a distinctive RFLP when
      digested by HindIII and EcoRV, and SDS-PAGE profile showed distinctive proteins
      expression as well. In vitro phage challenge showed a total reduction of E. coli
      O157:H7, Salmonella Typhimurium and Saintpaul counts at 2 h, whereas for
      Salmonella Montevideo a reduction and retardation growth, at a multiplicity of
      infection (MOI) of 100, was observed; however, under a MOI of 10 000, no viable
      cells were detected after 4 h. The wide host ranges of these phages suggested
      they could be used for simultaneous biocontrol of some Salmonella serotypes and
      E. coli O157:H7.

PMID- 22145761
TI  - Short-term outcome following percutaneous tibial nerve stimulation for faecal
      incontinence: a single-centre prospective study.
AB  - AIM: Percutaneous tibial nerve stimulation (PTNS) is increasingly being used as a
      treatment for faecal incontinence (FI). The evidence for its efficacy is limited
      to a few studies involving small numbers of patients. The aim of the study was to
      assess the efficacy of PTNS in patients with urge, passive and mixed FI. METHOD:
      A prospective cohort of 100 patients with FI was studied. Continence scores were
      determined before treatment and following 12 sessions of PTNS using a validated
      questionnaire [Cleveland Clinic Florida (CCF)-FI score]. The deferment time and
      average number of weekly incontinence episodes before and after 12 sessions of
      treatment were estimated from a bowel dairy kept by the patient. Quality of life
      was assessed prior to and on completion of 12 sessions of PTNS using a validated
      questionnaire [Rockwood Faecal Incontinence Quality of Life (QoL)]. RESULTS: One
      hundred patients (88 women) of median age of 57 years were included. Patients
      with urge FI (n=25) and mixed FI (n=60) demonstrated a statistically significant
      improvement in the mean CCF-FI score (11.0 +/- 4.1 to 8.3 +/- 4.8 and 12.8 +/-
      3.7 to 9.1 +/- 4.4) with an associated improvement in the QoL score. This effect
      was not observed in patients with purely passive FI (n=15). CONCLUSION: The study
      demonstrates that PTNS benefits patients with urge and mixed FI, at least in the
      short term.

PMID- 22145763
TI  - Repair of chondral defects with allogenous chondrocyte-seeded hyaluronan/collagen
      II microspheres in a rabbit model.
AB  - Using a recently established method to prepare hyaluronan/collagen II (HA/Col II)
      microspheres for a novel biomaterial to couple with living cells/tissues, this
      animal model study evaluated the effects on a 4-week healing process of chondral
      defects by the implantation of allogenous chondrocyte-seeded HA/Col II
      microspheres that had been cultured in vitro for 7 days prior to implantation
      compared with unseeded HA/Col II microspheres or an untreated wound. Four weeks
      postsurgery, the untreated group's defect was filled with translucent soft
      tissue. At the same time, the edges and demarcation lines of the healing defects
      that were implanted with either HA/Col II microspheres or chondrocyte-seeded
      HA/Col II microspheres were infused yet recognizable. Furthermore, the new
      tissues were well integrated into the surrounding articular cartilage. Less
      glycosaminoglycan (GAG) staining was observed in the defects implanted with
      HA/Col II microspheres, which indicated that most of the repair tissues were
      derived from fibrocartilage formation. Conversely, more GAG staining appeared in
      the defect implanted with chondrocyte-seeded HA/Col II microspheres, which
      demonstrated a higher level of hyaline cartilage regeneration. Due to the short
      healing period assigned to this study, the repaired cartilage showed limited
      incorporation into the surrounding host cartilage and some loose connection to
      the subchondral bone.

PMID- 22145764
TI  - Do individuals with Williams syndrome possess absolute pitch?
AB  - Although absolute pitch (AP) is a rare skill in typical development, individuals
      with Williams syndrome (WS) are often referred to as possessing this musical
      ability. However, there is paucity of research on the topic. In this article, 2
      studies were conducted to evaluate AP in WS. In Study 1, seven musically trained
      individuals with WS, 14 musically trained typically developing controls matched
      for chronological age, and 2 experienced musicians with AP completed a pitch
      identification task. Although the task was a classical assessment of AP, it
      required participants to have musical knowledge, and the availability and
      accessibility of musically trained individuals with WS is very low. In Study 2, a
      paradigm suitable for evaluating AP in individuals without musical training was
      used, which made it possible to evaluate a larger group of participants with WS.
      A pitch memory test for isolated tones was presented to 27 individuals with WS,
      54 typically developing peers matched for chronological age, and the 2 musicians
      with AP. Both individuals with WS and their controls obtained low results in the
      two studies. They showed an arbitrary pattern of response, and their performance
      was far from that of musicians with AP. Therefore, participants with WS did not
      appear to possess AP. Unlike what is usually claimed, results suggest that AP is
      not a remarkable ability in WS and that, as in the typically developing
      population, this musical ability is also rare in individuals with WS.

PMID- 22145762
TI  - A diagnostic algorithm combining clinical and molecular data distinguishes
      Kawasaki disease from other febrile illnesses.
AB  - BACKGROUND: Kawasaki disease is an acute vasculitis of infants and young children
      that is recognized through a constellation of clinical signs that can mimic other
      benign conditions of childhood. The etiology remains unknown and there is no
      specific laboratory-based test to identify patients with Kawasaki disease.
      Treatment to prevent the complication of coronary artery aneurysms is most
      effective if administered early in the course of the illness. We sought to
      develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease
      patients from febrile controls to allow timely initiation of treatment. METHODS:
      Urine peptidome profiling and whole blood cell type-specific gene expression
      analyses were integrated with clinical multivariate analysis to improve
      differentiation of Kawasaki disease subjects from febrile controls. RESULTS:
      Comparative analyses of multidimensional protein identification using 23 pooled
      Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139
      candidate markers, of which 13 were confirmed (area under the receiver operating
      characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki
      disease and 30 febrile control urine peptidomes. Cell type-specific analysis of
      microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood
      samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The
      integration of the urine/blood based biomarker panels and a multivariate analysis
      of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki
      disease and 342 febrile control subjects to diagnose Kawasaki disease.
      CONCLUSIONS: A hybrid approach using a multi-step diagnostic algorithm
      integrating both clinical and molecular findings was successful in
      differentiating children with acute Kawasaki disease from febrile controls.

PMID- 22145765
TI  - Single cell DNA damage/repair assay using HaloChip.
AB  - The molecular level damage to DNA is important due to DNA's susceptibility to
      free radical attacks and crucial roles in maintaining cell functions. Although a
      panel of techniques can be used to detect DNA damages, most of them are limited
      due to low sensitivity, low throughput, incompatibility for automated data
      analysis, and labor-intensive operations. We have developed a cell array based
      DNA damage assay in which mammalian cells are attached on an array of
      microfabricated patterns through electrostatic interactions. After trapping
      patterned cells inside gels, damaged DNA fragment can diffuse out of the nucleus
      and form a halo around each cell inside gels. The halo array can be observed
      fluorescently after labeling DNA with ethidium bromide. DNA damages can be
      determined sensitively at the single cell level, accurately due to the symmetric
      shape of the halo, and automatically due to the spatial registry of each cell and
      the nonoverlapping halos surrounding cells. The HaloChip can be used to detect
      DNA damages caused by chemicals and ultraviolet and X-ray irradiations with high
      efficiency. A major advantage of HaloChip is the ability to increase throughout
      by spatially encoding multiple dosing conditions on the same chip. Most
      importantly, the method can be used to measure variations in response to DNA
      damaging agents within the same cell population. Compared with halo assay or
      comet assay alone, this method allows automated analysis of a million cells
      without an overlapping issue. Compared with the microwell array based comet
      assay, this method can selectively capture and analyze cells, and the results can
      be easily analyzed to provide precise information on DNA damage. This method can
      be used in a broad range of clinical, epidemiological, and experimental settings.

PMID- 22145766
TI  - Amitriptyline may have a supportive role in cancer treatment by inhibiting
      glutathione S-transferase pi (GST-pi) and alpha (GST-alpha).
AB  - A tricyclic anti-depressant, amitriptyline, is a highly prescribed drug for
      cancer patients for mood elevation but there are limited studies about the
      interaction of amitriptyline with glutathione S-transferases pi (GST-pi) and
      glutathione S-transferases alpha (GST-alpha). GST isozymes have been implicated
      in chemotherapeutic drug resistance. We demonstrated that the concentration
      dependent inhibition of GST-pi and GST-alpha by amitriptyline followed inverse
      hyperbolic inhibition curves with IC(50) values of 5.54 and 8.32 mM,
      respectively. When the varied substrate was GSH, amitriptyline inhibited both
      isozymes competitively and similar K(i) values were found for GST-pi (K(i) = 1.61
      +/- 0.17 mM) and GST-alpha (K(i) = 1.45 +/- 0.20 mM). On the other hand, when the
      varied substrate was CDNB, the inhibition types were non-competitive for GST-pi
      (K(i) = 1.98 +/- 0.31 mM) and competitive for GST-alpha (K(i) = 1.57 +/- 0.16
      mM). Amitriptyline, in addition to its antidepressant effect, might also have a
      minor supportive role on the effectiveness of the anticancer drugs by decreasing
      their elimination through inhibiting GST-pi and GST-alpha.

PMID- 22145767
TI  - Impact of a collagen matrix on early healing, aesthetics and patient morbidity in
      oral mucosal wounds - a randomized study in humans.
AB  - AIM: To test whether a collagen matrix (CM) can improve early wound healing and
      aesthetics, and decrease wound sensitivity compared with spontaneous healing.
      METHODS: In 15 volunteers, 6-mm punch biopsies were harvested at both palatal
      sites. A CM was sutured in one site; the other one was left untreated (control).
      Measurements included the remaining defect area, the colour match to surrounding
      tissue and somatosensory parameters at various time-points (pre-operative, post
      operative, 4, 8, 15, 29 days). RESULTS: The defect area decreased over time for
      both treatments. Re-epithelization was completed in all subjects by day 15. The
      defect area was significantly smaller for CM (mean +/- SD: 19.3 +/- 3.4 mm(2))
      compared with control (21.3 +/- 3.3 mm(2)) at day 4 (p < 0.05), and at day 8 (CM:
      11.7 +/- 2.5 mm(2) ; control: 13.6 +/- 2.9 mm(2) ; p < 0.01). The colour match
      was more favourable for CM at day 4, 8 and 29 (p > 0.05). Somatosensory
      measurements revealed slightly lower wound sensitivity at day 4 for CM compared
      with control. CONCLUSIONS: The use of CM can enhance wound healing compared with
      spontaneous healing during the first week. This was mainly documented by a faster
      re-epithelization. Colour match and wound sensitivity measurements did not reach
      statistical significance between CM and control sites.

PMID- 22145768
TI  - The working alliance in a randomized controlled trial comparing online with face
      to-face cognitive-behavioral therapy for depression.
AB  - BACKGROUND: Although numerous efficacy studies in recent years have found
      internet-based interventions for depression to be effective, there has been scant
      consideration of therapeutic process factors in the online setting. In face-to
      face therapy, the quality of the working alliance explains variance in treatment
      outcome. However, little is yet known about the impact of the working alliance in
      internet-based interventions, particularly as compared with face-to-face therapy.
      METHODS: This study explored the working alliance between client and therapist in
      the middle and at the end of a cognitive-behavioral intervention for depression.
      The participants were randomized to an internet-based treatment group (n = 25) or
      face-to-face group (n = 28). Both groups received the same cognitive behavioral
      therapy over an 8-week timeframe. Participants completed the Beck Depression
      Inventory (BDI) post-treatment and the Working Alliance Inventory at mid- and
      post- treatment. Therapists completed the therapist version of the Working
      Alliance Inventory at post-treatment. RESULTS: With the exception of therapists'
      ratings of the tasks subscale, which were significantly higher in the online
      group, the two groups' ratings of the working alliance did not differ
      significantly. Further, significant correlations were found between clients'
      ratings of the working alliance and therapy outcome at post-treatment in the
      online group and at both mid- and post-treatment in the face-to-face group.
      Correlation analysis revealed that the working alliance ratings did not
      significantly predict the BDI residual gain score in either group. CONCLUSIONS:
      Contrary to what might have been expected, the working alliance in the online
      group was comparable to that in the face-to-face group. However, the results
      showed no significant relations between the BDI residual gain score and the
      working alliance ratings in either group. TRIAL REGISTRATION:
      ACTRN12611000563965.

PMID- 22145769
TI  - Galeal/periosteal rotation flaps: a novel technique for covering exposed forehead
      bone.

PMID- 22145770
TI  - Regenerative tendon and ligament healing: opportunities with recombinant human
      platelet-derived growth factor BB-homodimer.
AB  - Intrinsic tendon healing in response to injury is a reparative process that often
      results in formation of scar tissue with functional and mechanical properties
      inferior to those of the native tendon. Development of therapies that can promote
      regenerative, rather than reparative, healing hold the promise of improving
      patient recovery from tendon and ligament injuries by producing tissue that is
      morphologically and functionally equivalent to the native tissue. One therapeutic
      approach that has been a frequent topic of investigation in the preclinical
      literature is the use of recombinant human platelet-derived growth factor-BB
      (rhPDGF-BB) to augment tendon and ligament repair. The chemotactic, mitogenic,
      and pro-angiogenic properties of rhPDGF-BB have been shown to result in
      recruitment and proliferation of tenogenic cells and a commensurate boost in
      extracellular matrix deposition and organization, improving the morphological and
      biomechanical properties of healing tendons and ligaments. The outcomes of the
      preclinical studies reviewed here strongly suggest that rhPDGF-BB will provide a
      new therapeutic opportunity to improve the treatment of injured tendons and
      ligaments.

PMID- 22145772
TI  - The effect of Crocus sativus extract on human lymphocytes' cytokines and T helper
      2/T helper 1 balance.
AB  - The effects of macerated extracts of Crocus sativus (Family Iridaceae) (saffron)
      on cell viability and cytokine release of stimulated peripheral blood mononuclear
      cells by phytohemagglutinin (PHA) and nonstimulated cells were examined. The
      effects of three concentrations of macerated extract, dexamethasone, and saline
      on cell viability and production of cytokines, including interleukin (IL)-4, IL
      10, and interferon-gamma (IFN-gamma) were evaluated. In cells stimulated with
      PHA, different concentrations of the extract significantly inhibited cell
      viability of lymphocytes (P<.001 for all concentrations). High concentrations of
      the extract (500 MUg/mL) also inhibited secretion of IFN-gamma in stimulated
      cells and IL-10 secretion in both stimulated and nonstimulated cells (P<.05 for
      all cases). The effects of high and low concentrations of the extract (500 and 50
      MUg/mL, respectively) on IL-4 secretion were lower than that of dexamethasone
      (P<.05 to P<.001). The extract showed a stimulatory effect on IFN-gamma and IL-4
      secretion in nonstimulated cells. The ratios of IFN-gamma to IL-4 in the presence
      of all concentrations of saffron on stimulated cells were significantly higher
      than for the control group (P<.05 to P<.01). These results indicated that the
      extract of saffron leads to increased ratio of IFN-gamma to IL-4.

PMID- 22145771
TI  - Anti-inflammatory effect of heme oxygenase-1 toward Porphyromonas gingivalis
      lipopolysaccharide in macrophages exposed to gomisins A, G, and J.
AB  - Periodontitis, a chronic inflammatory periodontal disease that develops from
      gingivitis, is caused by periodontal pathogenic bacteria such as Porphyromonas
      gingivalis. Recent studies have focused on the antioxidant, anti-human
      immunodeficiency virus, anticarcinogenic, and anti-inflammatory properties of
      gomisins. However, the anti-inflammatory activities of gomisin plants through
      heme oxygenase-1 (HO-1) signals remain poorly defined. We found that gomisins'
      anti-inflammatory activity occurs via the induction of HO-1 expression. Gomisins
      G and J inhibit the production of the pro-inflammatory cytokines tumor necrosis
      factor-alpha, interleukin-1beta, and interleukin-6 and also block nuclear factor
      kappaB activation in Raw264.7 cells stimulated with P. gingivalis
      lipopolysaccharide. Furthermore, pro-inflammatory cytokine production is
      inhibited through the induction of HO-1 expression. HO-1 expression is induced by
      all gomisins, but their anti-inflammatory activity via HO-1 signaling is observed
      with gomisins G and J, and not A. We found that gomisins G and J extracted from
      Schisandria chinensis can inhibit the P. gingivalis lipopolysaccharide induced
      inflammatory responses in Raw264.7 cells.

PMID- 22145773
TI  - A polysaccharide isolated from Ecklonia cava fermented by Lactobacillus brevis
      inhibits the inflammatory response by suppressing the activation of nuclear
      factor-kappaB in lipopolysaccharide-induced RAW 264.7 macrophages.
AB  - We previously reported that the increment of carbohydrate content in the
      Viscozyme((r)) L (Novozyme Corp., Oklahoma City, OK, USA) extract of
      Lactobacillus brevis-fermented Ecklonia cava affected the inhibition of nitric
      oxide (NO) production and that it might be related to the polysaccharide
      compound. However, there is no report of anti-inflammatory effects of the
      polysaccharide or its biological mechanism. Here, we investigated the anti
      inflammatory effects of the polysaccharide and its biological mechanism in
      lipopolysaccharide (LPS)-activated RAW 264.7 cells. The polysaccharide isolated
      from the Viscozyme extract of L. brevis-fermented E. cava (VLFEP) dose
      dependently decreased LPS-stimulated NO production without cytotoxicity. Also,
      VLFEP significantly decreased the production of prostaglandin E(2) (PGE(2)) at
      the 100 MUg/mL concentration. In addition, VLFEP dose-dependently decreased the
      protein and mRNA expressions of inducible NO synthase, whereas it slightly
      decreased those of cyclooxygenase 2 and only at the 100 MUg/mL concentration.
      Moreover, VLEFP dose-dependently decreased the productions and/or mRNA
      expressions of tumor necrosis factor-alpha and interleukin-6, compared with those
      of LPS only-stimulated cells. In further experiments, VLFEP considerably reduced
      the phosphorylation and degradation of inhibitory kappaB as well as the
      translocation of nuclear transcription factor-kappaB (NF-kappaB) p65 into the
      nucleus, and its DNA binding was markedly induced by LPS stimulation. This study
      suggests that VLFEP exerts anti-inflammatory effects by down-regulating the
      production and expression of pro-inflammatory cytokines and mediators via
      inhibiting the NF-kappaB pathway in LPS-stimulated RAW 264.7 cells.

PMID- 22145774
TI  - Chronic intake of fractionated yellow pea flour reduces postprandial energy
      expenditure and carbohydrate oxidation.
AB  - Effects of dietary fibers on human postprandial energetics remain undefined. The
      objective of the present study was to explore effects of whole yellow pea flour
      (WPF) and fractionated pea flour (FPF) on postprandial energy expenditure,
      substrate utilization, and hepatic triglyceride synthesis rate. Using a crossover
      diet controlled design, 23 overweight men and women received muffins containing
      WPF, FPF, and white wheat flour (WF) for 28 days, followed by 28-day washout
      periods. Subjects received 50 g/day WPF and WF. Given that FPF is approximately
      84% fiber, the amount of FPF administered to volunteers was equivalent to the
      amount of pea-derived fiber in the WPF treatment. Four weeks of FPF consumption
      reduced (P=.007) total postprandial energy expenditure (333.0+/-3.6 kcal/330
      minutes) compared with WF (349.3+/-3.6 kcal/330 minutes). When values were
      normalized to the level of food energy consumed, FPF (4.6+/-0.3%) decreased
      (P=.018) the thermic effect of food (TEF) compared with WF (5.7+/-0.3%).
      Carbohydrate oxidation tended to be lower (P=.075) with FPF (44.7+/-2.1 g/330
      minutes) versus WF (51.2+/-0.1.9 g/330 minutes). WPF had no effect on total
      energy expenditure, TEF, or carbohydrate oxidation. Only after 370 minutes was
      cumulative oxidation of [1-(13)C]palmitic acid higher (P=.045) in the WPF group
      (0.96+/-0.05%) compared with FPF (0.81+/-0.05%). Neither treatment had any effect
      on hepatic triglyceride synthesis rate. In conclusion, chronic ingestion of
      different fractions of yellow peas imposes distinctive effects on postprandial
      energy expenditure and substrate utilization.

PMID- 22145775
TI  - Clinical and microbial evaluation of the effects on gingivitis of a mouth rinse
      containing an Enteromorpha linza extract.
AB  - Enteromorpha linza, a green alga, has been recognized as a potential source of
      natural antimicrobial and antifungal compounds. We previously reported that an E.
      linza extract strongly inhibited the growth of Prevotella intermedia and
      Porphyromonas gingivalis. The principal objective of this study was to evaluate
      the clinical effect of a mouth rinse containing the E. linza extract on
      gingivitis disease, as measured by the plaque index (PI), gingival index (GI),
      and bleeding on probing (BOP), and on two bacterial strains (P. intermedia and P.
      gingivalis), in comparison with Listerine((r)) (Listerine-Korea, Seoul, Korea),
      which was used as a positive control. In total, 55 subjects were recruited into
      active participation in this clinical study. The PI, GI, BOP, and bacterial
      strains were then evaluated over a test period of 6 weeks. After 1, 2, 4, and 6
      weeks, the same clinical indices were recorded, and the levels of P. intermedia
      and P. gingivalis were quantified via real-time polymerase chain reaction. At the
      end of the study, the group using the mouth rinse containing the E. linza extract
      evidenced significant reductions in the clinical indices (PI, GI, and BOP) and P.
      gingivalis compared with baseline values. Moreover, E. linza extract containing
      mouth rinse produced effects similar to those of Listerine. Overall, these
      results indicate that a mouth rinse containing E. linza extract significantly
      reduces plaque, improves the condition of gingival tissues, and reduces bleeding.
      Additionally, E. linza extract mouth rinse significantly inhibits P. gingivalis
      and P. intermedia. Thus, this clinical study demonstrated that the twice-daily
      use of an E. linza extract mouth rinse can inhibit and prevent gingivitis.

PMID- 22145776
TI  - Influence of sildenafil on micturition and urethral tone in ovariectomized and
      non-ovariectomized mice.
AB  - INTRODUCTION: Nitric oxide synthases (NOSs) and estrogen receptors are expressed
      in the female urethra. AIM: We aimed to assess the impact of sildenafil on
      micturition behavior, urethral tone according to the hormonal status and to
      determine the implications of the neuronal isoform of NOS (nNOS). METHODS: Four
      week-old C57/BL6 female mice were sham-operated or ovariectomized. Six weeks
      later, they were injected intraperitoneally by any combination of sildenafil, 7
      nitroindazole (7-NI)-a potent selective nNOS inhibitor-or the corresponding
      vehicles. The mice were then subjected to micturition behavior and leak point
      pressure studies. Urethral histomorphometry was performed. MAIN OUTCOME MEASURES:
      The main outcome measures were micturition behavior, leak point pressure, and
      histomorphometry. RESULTS: In sham-operated and ovariectomized animals,
      sildenafil did not impact micturition, although it decreased urethral resistance
      10-fold. nNOS inhibition by 7-NI reduced the number of micturitions and increased
      residual volume and leak point pressure. It abrogated sildenafil-induced drop in
      urethral resistances. Hormonal status did not influence the structure of the
      urethral layers. CONCLUSIONS: Irrespective of the hormonal status, sildenafil
      decreased leak point pressure by a nNOS-mediated mechanism.

PMID- 22145778
TI  - Microscopic examination of bone marrow aspirate in healthy adults - comparison of
      two techniques of slide preparation.
AB  - INTRODUCTION: According to the International Council for Standardization in
      Hematology (ICSH) guidelines for the standardization of bone marrow specimens and
      reports, smears from bone marrow aspirates for microscopic examination should be
      prepared using two techniques simultaneously: the wedge-spread and the crush
      technique. However, the outcomes of these techniques have never been compared.
      METHODS: We investigated the bone marrow of 105 adult, haematologically healthy
      subjects, using bone marrow smears prepared via both techniques simultaneously.
      RESULTS: Comparison of the two techniques revealed significant differences in
      terms of the composition of bone marrow cells. Only the percentages of
      lymphocytes, mature eosinophils and basophils did not differ significantly. The
      reference ranges for each technique were established. CONCLUSIONS: The crush
      technique seems to be more valuable than the wedge-spread technique because of
      the lack of a blood dilution effect and better assessment of megakaryopoiesis. We
      recommend the crush technique for the evaluation of the percentage composition of
      bone marrow cells. In a very small number of patients with irregular cell
      localization in the bone marrow particles, the wedge-spread technique may be more
      beneficial for the assessment of total cellularity. The recommendation to
      routinely prepare slides using both of these techniques is fully justified.

PMID- 22145777
TI  - Inhibition of protein translocation at the endoplasmic reticulum promotes
      activation of the unfolded protein response.
AB  - Selective small-molecule inhibitors represent powerful tools for the dissection
      of complex biological processes. ES(I) (eeyarestatin I) is a novel modulator of
      ER (endoplasmic reticulum) function. In the present study, we show that in
      addition to acutely inhibiting ERAD (ER-associated degradation), ES(I) causes
      production of mislocalized polypeptides that are ubiquitinated and degraded.
      Unexpectedly, our results suggest that these non-translocated polypeptides
      promote activation of the UPR (unfolded protein response), and indeed we can
      recapitulate UPR activation with an alternative and quite distinct inhibitor of
      ER translocation. These results suggest that the accumulation of non-translocated
      proteins in the cytosol may represent a novel mechanism that contributes to UPR
      activation.

PMID- 22145779
TI  - Implementation of the "loaded implant" model in the rat using a miniaturized
      setup--description of the method and first results.
AB  - OBJECTIVE: To miniaturize the "loaded implant" model to permit its application to
      small rodents. In this model, two titanium implants are placed 8 mm apart with
      their heads protruding from the skin and are forced together by a dedicated
      actuator. To assess the effect of (i) the post-implantation healing period and
      the duration of stimulation and (ii) the intratissular strain level on the
      microtomographical bone parameters BV/TV, Tb.N., Tb.Th. and BIC. MATERIALS AND
      METHODS: Implants, 1 * 8 mm, were machined, inserted into the tibiae of rats and
      activated. A total of 123 animals were used. In series 1, the implants were left
      to heal for 2/4 weeks and then loaded to generate intratissular strains of 1125
      +/- 5% MUepsilon for 4/8 weeks. Series 2 had their implants loaded to 750, 1500
      and 2250 +/- 5% MUepsilon, respectively. RESULTS: Bone to implant contact
      increased upon loading. In series 1, no difference was observed regarding the
      duration of healing or the stimulation period. In series 2, at 750 MUepsilon, the
      bone parameters did not differ from baseline. At 1500 MUepsilon, all four
      parameters increased. At 2250 MUepsilon, three of four parameters decreased
      relative to 1500 MUepsilon. CONCLUSIONS: (i) The loaded implant model can be
      miniaturized to the millimeter range; (ii) in the present model, implant
      activation beyond 4 weeks did not affect the bone parameters; (iii) mechanical
      stimulation increased bone to implant contact by up to 20%; (iv) the results
      obtained are consistent with the concept of an anabolic effect from 750 to 1500
      MUepsilon and deleterious effects at strains in the 2250 MUepsilon range; and (v)
      strains at 2250 MUepsilon did not lead to implant dis-integration.

PMID- 22145780
TI  - Polynuclear and polymeric gadolinium acetate derivatives with large
      magnetocaloric effect.
AB  - Two ferromagnetic MU-oxo(acetate)-bridged gadolinium complexes
      [Gd(2)(OAc)(2)(Ph(2)acac)(4)(MeOH)(2)] (1) and [Gd(4)(OAc)(4)(acac)(8)(H(2)O)(4)]
      (2) and two polymeric Gd(III) chains [Gd(OAc)(3)(MeOH)](n) (3) and
      [Gd(OAc)(3)(H(2)O)(0.5)](n) (4) (Ph(2)acacH = dibenzoylmethane; acacH =
      acetylacetone) are reported. The magnetic studies reveal that the tiny difference
      in the Gd-O-Gd angles (Gd...Gd distances) in these complexes cause different
      magnetic coupling. There exist ferromagnetic interactions in 1-3 due to the
      presence of the larger Gd-O-Gd angles (Gd...Gd distances), and antiferromagnetic
      interaction in 4 when the Gd-O-Gd angle is smaller. Four gadolinium acetate
      derivatives display large magnetocaloric effect (MCE). The higher magnetic
      density or the lower M(W)/N(Gd) ratio they have, the larger MCE they display.
      Complex 4 has the highest magnetic density and exhibits the largest MCE (47.7 J
      K(-1) kg(-1)). In addition, complex 3 has wider temperature and/or field scope of
      application in refrigeration due to the dominant ferromagnetic coupling.
      Moreover, the statistical thermodynamics on entropy was successfully applied to
      simulate the MCE values. The results are quite in agreement with those obtained
      from experimental data.

PMID- 22145782
TI  - Rhodium(0) nanoparticles supported on nanocrystalline hydroxyapatite: highly
      effective catalytic system for the solvent-free hydrogenation of aromatics at
      room temperature.
AB  - The hydrogenation of aromatics under mild conditions remains a challenge in the
      fields of synthetic and petroleum chemistry. Described herein is a new catalytic
      material that shows excellent catalytic performance in terms of activity,
      selectivity, and reusability in the hydrogenation of aromatics in solvent-free
      systems under mild conditions. The catalyst, consisting of rhodium nanoparticles
      supported on nanocrystalline hydroxyapatite, can quantitatively hydrogenate neat
      benzene to cyclohexane with exceptionally high rates (initial TOF > 10(3) h(-1))
      at 298 K and 3 bars of initial H(2) pressure. This new material maintains its
      inherent catalytic activity after several reuses. Importantly, catalyst
      preparation does not require elaborate procedures because the active metal
      nanoparticles are readily formed from the in situ reduction of Rh(3+)-exchanged
      hydroxyapatite while submerged in the aromatic solvent at room temperature under
      3 bars of H(2) pressure.

PMID- 22145781
TI  - Drug exposure and pregnancy outcome in Mozambique.
AB  - BACKGROUND: The intake of medicines during pregnancy can have negative or toxic
      effects on the fetus, possibly leading to adverse pregnancy outcomes. OBJECTIVE:
      The aim of this study was to describe the level of drug exposure during pregnancy
      in a rural area of Mozambique and its relation to pregnancy outcome. METHODS: A
      total of 3105 pregnant women were interviewed in a cohort study. Information on
      disease, treatments received during pregnancy, and pregnancy outcome was
      collected. Newborns were examined at birth for clinical signs, birthweight, and
      presence of any congenital malformation. RESULTS: Malaria and sexually
      transmitted diseases were the most frequently reported diseases (30.5% and 24.1%,
      respectively), and 41% (1276/3105) of participants reported at least one drug
      exposure. The mean number of drugs taken per pregnant woman was 3.9 (SD 2.1).
      Antibiotics were the most commonly (41.2%) reported agents, followed by
      antimalarials (23.8%). There were more stillbirths (p < 0.007) among those
      reporting to be exposed to drugs compared with no exposure. Polydactyly was the
      most frequent malformation observed. CONCLUSIONS: Drug exposure during pregnancy,
      including drugs with recognized potential pregnancy risk, was high in this rural
      area of southern Africa. The association of stillbirths with drug exposure might
      be a consequence of the disease that led to drug administration, although a
      direct causality of the drugs cannot be excluded. These findings emphasize the
      need for reinforcing pharmacovigilance systems in rural Africa, especially, or at
      least, in pregnant women.

PMID- 22145783
TI  - Patient characteristics, comorbidities, and medication use for children with ADHD
      with and without a co-occurring reading disorder: A retrospective cohort study.
AB  - BACKGROUND: Children and adolescents with attention-deficit/hyperactivity
      disorder (ADHD) often have a co-occurring reading disorder (RD). The purpose of
      this research was to assess differences between children with ADHD without RD
      (ADHD-only) and those with ADHD and co-occurring RD (ADHD+RD). METHODS: Using
      data from the U.S. Thomson Reuter Marketscan(r) Databases for the years 2005
      through 2007, this analysis compared the medical records--including patient
      demographics, comorbidities, and medication use--of children (age < 18) with ADHD
      only to those with ADHD+RD. RESULTS: Patients with ADHD+RD were significantly
      younger, more likely to have received a procedure code associated with formal
      psychological or non-psychological testing, and more likely to have been
      diagnosed with comorbid bipolar disorder, conduct disorder, or depression. They
      were no more likely to have received an antidepressant, anti-manic (bipolar), or
      antipsychotic, and were significantly less likely to have received a prescription
      for a stimulant medication. CONCLUSIONS: Relying on a claims database, there
      appear to be differences in the patient characteristics, comorbidities, and
      medication use when comparing children with ADHD-only to those with ADHD+RD.

PMID- 22145785
TI  - Enhancement of iron(II)-dependent reduction of nitrite to nitric oxide by
      thiocyanate and accumulation of iron(II)/thiocyanate/nitric oxide complex under
      conditions simulating the mixture of saliva and gastric juice.
AB  - Iron(III) ingested as a food component or supplement for iron deficiencies can
      react with salivary SCN(-) to produce Fe(SCN)(2+) and can be reduced to iron(II)
      by ascorbic acid in the stomach. Iron(II) generated in the stomach can react with
      salivary nitrite and SCN(-) to produce nitric oxide (NO) and FeSCN(+),
      respectively. The purpose of this investigation is to make clear the reactions
      among nitrite, SCN(-), iron ions, and ascorbic acid under conditions simulating
      the mixture of saliva and gastric juice. Iron(II)-dependent reduction of nitrite
      to NO was enhanced by SCN(-) in acidic buffer solutions, and the oxidation
      product of iron(II) reacted with SCN(-) to produce Fe(SCN)(2+). Almost all of the
      NO produced was autoxidized to N(2)O(3) under aerobic conditions. Iron(II)
      dependent production of NO was also observed in acidified saliva. Under anaerobic
      conditions, NO transformed Fe(SCN)(2+) and FeSCN(+) to Fe(SCN)NO(+) in acidic
      buffer solutions. Fe(SCN)NO(+) was also formed under aerobic conditions when
      excess ascorbic acid was added to iron(II)/nitrite/SCN(-) systems in acidic
      buffer solutions and acidified saliva. The Fe(SCN)NO(+) formed was transformed to
      Fe(SCN)(2+) and iron(III) at pH 2.0 and pH 7.4, respectively, by O(2). Salivary
      glycoproteins could complex with iron(III) in the stomach preventing the
      formation of Fe(SCN)(2+). Ascorbic acid reduced iron(III) to iron(II) to react
      with nitrite and SCN(-) as described above. The above results suggest (i) that
      iron(II) can have toxic effects on the stomach through the formation of reactive
      nitrogen oxide species from NO when supplemented without ascorbic acid and
      through the formation of both reactive nitrogen oxide species and Fe(SCN)NO(+)
      when supplemented with ascorbic acid, and (ii) that the toxic effects of
      iron(III) seemed to be smaller than and similar to those of iron(II) when
      supplemented without and with ascorbic acid, respectively. Possible mechanisms
      that cause oxidative stress on the stomach through Fe(SCN)NO(+) are discussed.

PMID- 22145784
TI  - Regional particle size dependent deposition of inhaled aerosols in rats and mice.
AB  - CONTEXT: The current data analysis tools in nuclear medicine have not been used
      to evaluate intra organ regional deposition patterns of pharmaceutical aerosols
      in preclinical species. OBJECTIVE: This study evaluates aerosol deposition
      patterns as a function of particle size in rats and mice using novel image
      analysis techniques. MATERIALS AND METHOD: Mice and rats were exposed to
      radiolabeled polydisperse aerosols at 0.5, 1.0, 3.0, and 5.0 um MMAD followed by
      SPECT/CT imaging for deposition analysis. Images were quantified for both macro
      deposition patterns and regional deposition analysis using the LRRI-developed
      Onion Model. RESULTS: The deposition fraction in both rats and mice was shown to
      increase as the particle size decreased, with greater lung deposition in rats at
      all particle sizes. The Onion Model indicated that the smaller particle sizes
      resulted in increased peripheral deposition. DISCUSSION: These data contrast the
      commonly used 10% deposition fraction for all aerosols between 1.0 and 5.0 um and
      indicate that lung deposition fraction in this range does change with particle
      size. When compared to historical data, the 1.0, 3.0, and 5.0 um particles result
      in similar lung deposition fractions; however, the 0.5 um lung deposition
      fraction is markedly different. This is probably caused by the current aerosols
      that were polydisperse to reflect current pharmaceutical aerosols, while the
      historical data were generated with monodisperse aerosols. CONCLUSION: The
      deposition patterns of aerosols between 0.5 and 5.0 um showed an increase in both
      overall and peripheral deposition as the particle size decreased. The Onion Model
      allows a more complex analysis of regional deposition in preclinical models.

PMID- 22145786
TI  - Three-dimensional multimodal image non-rigid registration and fusion in a High
      Intensity Focused Ultrasound system.
AB  - High Intensity Focused Ultrasound (HIFU) has been successfully applied in tumor
      therapy. For a successful HIFU therapy, it is crucial to localize the tumor
      region accurately. In this paper, we present a semi-automatic non-rigid
      registration method for implementing image guided surgery navigation and
      localization by matching pre-operative CT/MR images and intra-operative
      ultrasound images. The global motion of the target is modeled by an affine
      transformation, while the local deformation of the target is described by Free
      Form Deformation (FFD) based on B-splines. The results of our experiments on
      simulated and real data show that the non-rigid registration method based on HPV
      interpolation (partial volume based on the Hanning windowed sinc function) is
      effective at restraining local extrema and improves the accuracy of registration
      results. A preliminary clinical validation of the use of the non-rigid
      registration method in image guided localization of a HIFU system is also
      reported.

PMID- 22145787
TI  - Image guided surgery of the lateral skull base: testing a new dental splint
      registration device.
AB  - OBJECTIVE: The widespread use of image guided surgery in the frontolateral skull
      base region has been limited by the need for a reliable and non-invasive
      registration procedure that provides sub-millimetric accuracy. We developed and
      validated preclinically a non-invasive, easy-to-use registration device based on
      a dental splint with a laterally mounted fiducial carrier. METHODS: Repeated
      accuracy measurements were performed on six titanium target fiducials which were
      screwed into the lateral skull base region of a cadaver head and could be
      unequivocally identified both on the CT image and in reality. The system accuracy
      was evaluated by determining the deviation of the real target position from the
      position indicated in the CT scan. The accuracy of the dental splint-based
      registration was compared to that of two standard registration procedures:
      contour-based laser surface registration and fixed marker registration. RESULTS:
      The mean accuracy of 0.55+/-0.28 mm obtained when using the maxillary splint
      device was similar to that obtained with the "gold standard" registration using
      bone-implanted markers (0.33+/-0.26 mm), while being clearly superior to that
      obtained with contour-based laser surface registration (1.91+/-0.74 mm).
      CONCLUSIONS: Registration using the non-invasively fixed maxillary fiducial
      platform can provide sub-millimetric accuracy in the lateral skull base region.
      In vivo validation may prove dental splint-based registration to be an accurate
      and non-invasive alternative option for image guided surgery of the lateral skull
      base, and may facilitate the application of navigation systems in this delicate
      region.

PMID- 22145788
TI  - Computer-assisted patellar resection for total knee arthroplasty.
AB  - Incorrect patellar resection during total knee arthroplasty can lead to anterior
      knee pain, patellar maltracking, patellofemoral impingement, patellar fracture,
      component loosening and reduced range of motion. A computer-assisted surgery
      (CAS) system was developed to improve the accuracy of the patellar cut. Twelve
      cadaveric knee specimens (6 pairs) were surgically prepared and the patella
      resected by two senior orthopaedic residents using either a conventional sawguide
      technique (right knee) or a computer-assisted sawguide technique (left knee).
      Multiple cuts and measurements were permitted for the conventional technique, to
      reflect the clinical situation, whereas only a single cut was permitted for the
      CAS technique. Prior training had been provided on artificial bones for both
      techniques. Custom marker arrays were mounted on the sawguide and patella. The
      user positioned the sawguide based on a real-time display that compared the
      current sawguide plane to the ideal resection. The resulting mediolateral and
      superoinferior resection angles and central thickness were measured from CT scans
      of the specimens, relative to the anterior surface of the patella. Both
      techniques resulted in symmetric cuts (<7 degrees ). Repeatability in the
      mediolateral direction was better for the CAS technique than for the conventional
      technique (p<0.01). This study demonstrated that computer-assisted patellar
      resection is a feasible approach that can produce results equal to or better than
      those obtained with conventional techniques, even when the experimental
      conditions favor the conventional technique. Improvements in the CAS hardware
      could further improve the accuracy and usability of the system, resulting in
      reductions in postoperative complications. Patellar CAS could also serve as a
      valuable tool for feedback and training.

PMID- 22145789
TI  - Significance of measurements of herniary area and volume and abdominal cavity
      volume in the treatment of incisional hernia: application of CT 3D reconstruction
      in 17 cases.
AB  - OBJECTIVE: To investigate the value of CT 3D reconstruction in the diagnosis and
      treatment of incisional hernia and the related factor of abdominal cavity volume.
      METHODS: Abdominal wall defect and herniary volume were measured using 3D
      reconstruction based on plain CT scans in 17 patients with incisional hernias.
      RESULTS: The herniary diameter, area and volume could be measured in the 17
      patients and the abdominal cavity volume was also measured in 10 patients using
      the 3D reconstruction technique. The correlation indices of the abdominal cavity
      volume with the patient's height, weight and body mass index (BMI) were all less
      than 0.01. CONCLUSION: Herniary area and volume and abdominal cavity volume can
      be accurately calculated through CT 3D reconstruction. The patch area should be
      more than 5 times as large as the defect area; combined with the perioperative
      overlap margin measurement method, this results in more scientific surgical
      management. The ratio of the herniary volume to the abdominal cavity volume may
      be conducive to preoperative assessment of the risk of abdominal compartment
      syndrome (ACS); however, the ratio that may lead to postoperative ACS remains to
      be determined. There are correlations of abdominal cavity volume with patient
      height, weight and BMI, especially with weight. We therefore propose that the
      abdominal cavity volume should be evaluated with internationally accepted
      indices.

PMID- 22145791
TI  - Perception of cancer and inconsistency in medical information are associated with
      decisional conflict: a pilot study of men with prostate cancer who undergo active
      surveillance.
AB  - Men with prostate cancer who choose active surveillance may experience anxiety
      and depression. Higher anxiety related to uncertainty surrounding cancer has been
      shown to increase the likelihood of choosing active treatment in the absence of a
      clinical indication. Certain characteristics, including physician influence and a
      neurotic personality, may also increase the risk of psychological distress. Our
      study identified particular areas that may affect the degree of satisfaction or
      uncertainty experienced by men choosing active surveillance. We showed that men
      with a positive outlook who perceived that they were receiving consistent medical
      information had improved ability to manage uncertainty and felt more in control
      of their decision-making. Men who were confident in their ability to manage
      prostate-related symptoms also had less insecurity with their decision.
      OBJECTIVE: To understand the factors associated with decision-making, we
      conducted a telephone-based survey as part of a pilot study to develop a
      psychoeducational intervention for men with prostate cancer who undergo active
      surveillance. PATIENTS AND METHODS: From 2007 to 2008, we conducted a cross
      sectional study of 34 individuals on active surveillance for prostate cancer. We
      examined how specific mental health, quality of life and sociodemographic
      characteristics relate to decision-making. Five validated decision-making scales
      were used as primary outcomes reflecting the amount of satisfaction, regret and
      conflict a participant experienced about his decision to undergo active
      surveillance. A multivariate regression model was developed to identify specific
      psychosocial factors related to the decision-making outcomes. RESULTS: Primary
      analyses focused on the decisional satisfaction and conflict measures, as the
      decisional regret measure showed poor reliability (alpha < 0.70) in this sample.
      Four psychosocial measures showed strong associations across the decision-making
      subscales, including the Fife Constructed Meaning Scale (Pearson r > 0.26),
      Mishel Uncertainty in Illness Scale - Inconsistency (r > 0.32), Mental Health
      Index-5 (r > 0.33), and Lepore self-efficacy for prostate symptom management
      scale (r > 0.33). Individuals with higher self-efficacy for prostate cancer
      symptom management (P = 0.02) and higher positive meaning for cancer (P = 0.03)
      were less likely to express decision-making conflict as the result of
      uncertainty. Individuals reporting higher positive meaning for cancer (P = 0.01)
      and less uncertainty in illness attributed to inconsistency (P = 0.02) were less
      likely to exhibit decision-making conflict related to the perceived effectiveness
      of treatment. CONCLUSIONS: Men choosing active surveillance represent a patient
      group with unique vulnerabilities that require new psychoeducational
      interventions to provide information and support that will maintain and improve
      quality of life. We describe specific characteristics that may put patients at
      higher risk during the decision-making process and indicate their increased need
      for such interventions.

PMID- 22145790
TI  - CXCR7 antagonism prevents axonal injury during experimental autoimmune
      encephalomyelitis as revealed by in vivo axial diffusivity.
AB  - BACKGROUND: Multiple Sclerosis (MS) is characterized by the pathological
      trafficking of leukocytes into the central nervous system (CNS). Using the murine
      MS model, experimental autoimmune encephalomyelitis (EAE), we previously
      demonstrated that antagonism of the chemokine receptor CXCR7 blocks endothelial
      cell sequestration of CXCL12, thereby enhancing the abluminal localization of
      CXCR4-expressing leukocytes. CXCR7 antagonism led to decreased parenchymal entry
      of leukocytes and amelioration of ongoing disease during EAE. Of note, animals
      that received high doses of CXCR7 antagonist recovered to baseline function, as
      assessed by standard clinical scoring. Because functional recovery reflects
      axonal integrity, we utilized diffusion tensor imaging (DTI) to evaluate axonal
      injury in CXCR7 antagonist- versus vehicle-treated mice after recovery from EAE.
      METHODS: C57BL6/J mice underwent adoptive transfer of MOG-reactive Th1 cells and
      were treated daily with either CXCR7 antagonist or vehicle for 28 days; and then
      evaluated by DTI to assess for axonal injury. After imaging, spinal cords
      underwent histological analysis of myelin and oligodendrocytes via staining with
      luxol fast blue (LFB), and immunofluorescence for myelin basic protein (MBP) and
      glutathione S-transferase-pi (GST-pi). Detection of non-phosphorylated
      neurofilament H (NH-F) was also performed to detect injured axons. Statistical
      analysis for EAE scores, DTI parameters and non-phosphorylated NH-F
      immunofluorescence were done by ANOVA followed by Bonferroni post-hoc test. For
      all statistical analysis a p < 0.05 was considered significant. RESULTS: In vivo
      DTI maps of spinal cord ventrolateral white matter (VLWM) axial diffusivities of
      naive and CXCR7 antagonist-treated mice were indistinguishable, while vehicle
      treated animals exhibited decreased axial diffusivities. Quantitative differences
      in injured axons, as assessed via detection of non-phosphorylated NH-F, were
      consistent with axial diffusivity measurements. Overall, qualitative myelin
      content and presence of oligodendrocytes were similar in all treatment groups, as
      expected by their radial diffusivity values. Quantitative assessment of
      persistent inflammatory infiltrates revealed significant decreases within the
      parenchyma of CXCR7 antagonist-treated mice versus controls. CONCLUSIONS: These
      data suggest that CXCR7 antagonism not only prevents persistent inflammation but
      also preserves axonal integrity. Thus, targeting CXCR7 modifies both disease
      severity and recovery during EAE, suggesting a role for this molecule in both
      phases of disease.

PMID- 22145792
TI  - Preconcentration and analysis of trace volatile carbonyl compounds.
AB  - We describe a preconcentration device that may be suitable for quantitative
      analysis of trace volatile ketones and aldehydes in ambient air as well as in
      human breath. The approach is based on microreactor chips fabricated from silicon
      wafers. The microreactors have thousands of micropillars in microfluidic channels
      for uniformly distributing a gaseous sample flowing through the chips. The
      surfaces of the micropillars are functionalized with a quaternary ammonium
      aminooxy salt, [2-(aminooxy)ethyl]-N,N,N-trimethylammonium iodide (ATM), for
      trapping trace ketones and aldehydes by means of oximation reactions. ATM adducts
      and unreacted ATM are eluted from the microreactor with less than 40 MUL of
      methanol and directly analyzed by nanospray Fourier transform ion cyclotron
      resonance (FTICR) mass spectrometry (MS). Ketones and aldehydes at levels of 1
      ppbv have been detected using this microreactor and FTICR-MS system.

PMID- 22145793
TI  - Neuropsychological sequelae following pediatric stroke: a nonlinear model of age
      at lesion effects.
AB  - AIM: The distribution and quality of brain recovery following pediatric arterial
      ischemic stroke remains controversial. The literature suggests that age at stroke
      may be an important modulator of neuropsychological outcome, with reports
      inferring either greater vulnerability or plasticity in the nascent brain. Our
      aim was to investigate neuropsychological outcomes following pediatric stroke in
      a clinical sample with reference to age at lesion, lesion laterality, elapsed
      time from stroke to assessment, and persistent neurological sequelae. METHODS:
      Using comprehensive neuropsychological assessment batteries, we investigated
      retrospectively a large (n = 44) and evenly distributed group of children who had
      ischemic stroke during "infancy" (1 month to 1 year), "early childhood" (1 to 6
      years), and "late childhood" (6 to 16 years). RESULTS: Children who suffered a
      stroke performed significantly worse on a range of neuropsychological measures
      when compared to a normative sample. However, children who suffered a stroke
      between 1 and 6 years old demonstrated better preserved neuropsychological
      profiles than either the earlier (before age 1) or later (after age 6) age
      groups. In addition, those children suffering a left hemisphere lesion performed
      more poorly on a range of neuropsychological measures than did children with
      right hemisphere lesions. INTERPRETATION: Age at stroke is an important
      determinant of recovery following insult and may modulate neuropsychological and
      cognitive outcome.

PMID- 22145794
TI  - Performance of four clinical decision rules in patients with malignancy and
      suspected pulmonary embolism.

PMID- 22145795
TI  - Heavy metal ion inhibition studies of human, sheep and fish alpha-carbonic
      anhydrases.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) were purified from sheep kidney (sCA IV),
      from the liver of the teleost fish Dicentrarchus labrax (dCA) and from human
      erythrocytes (hCA I and hCA II). The purification procedure consisted of a single
      step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The kinetic
      parameters of these enzymes were determined for their esterase activity with 4
      nitrophenyl acetate as substrate. The following metal ions, Pb(2+), Co(2+),
      Hg(2+), Cd(2+), Zn(2+), Se(2+), Cu(2+), Al(3+) and Mn(3+) showed inhibitory
      effects on these enzymes. The tested metal ions inhibited these CAs competitively
      in the low milimolar/submillimolar range. The susceptibility to various cations
      inhibitors differs significantly between these vertebrate alpha-CAs and is
      probably due to their binding to His64 or the histidine cluster.

PMID- 22145796
TI  - Impact of geriatric comorbidity and polypharmacy on cholinesterase inhibitors
      prescribing in dementia.
AB  - BACKGROUND: Although most guidelines recommend the use of cholinesterase
      inhibitors (ChEIs) for mild to moderate Alzheimer's Disease, only a small
      proportion of affected patients receive these drugs. We aimed to study if
      geriatric comorbidity and polypharmacy influence the prescription of ChEIs in
      patients with dementia in Germany. METHODS: We used claims data of 1,848 incident
      patients with dementia aged 65 years and older. Inclusion criteria were first
      outpatient diagnoses for dementia in at least three of four consecutive quarters
      (incidence year). Our dependent variable was the prescription of at least one
      ChEI in the incidence year. Main independent variables were polypharmacy (defined
      as the number of prescribed medications categorized into quartiles) and measures
      of geriatric comorbidity (levels of care dependency and 14 symptom complexes
      characterizing geriatric patients). Data were analyzed by multivariate logistic
      regression. RESULTS: On average, patients were 78.7 years old (47.6% female) and
      received 9.7 different medications (interquartile range: 6-13). 44.4% were
      assigned to one of three care levels and virtually all patients (92.0%) had at
      least one symptom complex characterizing geriatric patients. 13.0% received at
      least one ChEI within the incidence year. Patients not assigned to the highest
      care level were more likely to receive a prescription (e.g., no level of care
      dependency vs. level 3: adjusted Odds Ratio [OR]: 5.35; 95% CI: 1.61-17.81). The
      chance decreased with increasing numbers of symptoms characterizing geriatric
      patients (e.g., 0 vs. 5+ geriatric complexes: OR: 4.23; 95% CI: 2.06-8.69). The
      overall number of prescribed medications had no influence on ChEI prescription
      and a significant effect of age could only be found in the univariate analysis.
      Living in a rural compared to an urban environment and contacts to neurologists
      or psychiatrists were associated with a significant increase in the likelihood of
      receiving ChEIs in the multivariate analysis. CONCLUSIONS: It seems that not age
      as such but the overall clinical condition of a patient including care dependency
      and geriatric comorbidities influences the process of decision making on
      prescription of ChEIs.

PMID- 22145797
TI  - Protein conformational gating of enzymatic activity in xanthine oxidoreductase.
AB  - In mammals, xanthine oxidoreductase can exist as xanthine dehydrogenase (XDH) and
      xanthine oxidase (XO). The two enzymes possess common redox active cofactors,
      which form an electron transfer (ET) pathway terminated by a flavin cofactor. In
      spite of identical protein primary structures, the redox potential difference
      between XDH and XO for the flavin semiquinone/hydroquinone pair (E(sq/hq)) is
      ~170 mV, a striking difference. The former greatly prefers NAD(+) as ultimate
      substrate for ET from the iron-sulfur cluster FeS-II via flavin while the latter
      only accepts dioxygen. In XDH (without NAD(+)), however, the redox potential of
      the electron donor FeS-II is 180 mV higher than that for the acceptor flavin,
      yielding an energetically uphill ET. On the basis of new 1.65, 2.3, 1.9, and 2.2
      A resolution crystal structures for XDH, XO, the NAD(+)- and NADH-complexed XDH,
      E(sq/hq) were calculated to better understand how the enzyme activates an ET from
      FeS-II to flavin. The majority of the E(sq/hq) difference between XDH and XO
      originates from a conformational change in the loop at positions 423-433 near the
      flavin binding site, causing the differences in stability of the semiquinone
      state. There was no large conformational change observed in response to NAD(+)
      binding at XDH. Instead, the positive charge of the NAD(+) ring, deprotonation of
      Asp429, and capping of the bulk surface of the flavin by the NAD(+) molecule all
      contribute to altering E(sq/hq) upon NAD(+) binding to XDH.

PMID- 22145798
TI  - Fee comparisons of treatments for nonmelanoma skin cancer in a private practice
      academic setting.
AB  - OBJECTIVE: To compare fees for biopsy, treatment procedure, repair, and 2-month
      follow-up for nonmelanoma skin cancer (NMSC) treatments: electrodesiccation and
      curettage (ED&C), excision, and Mohs micrographic surgery (MMS). METHODS: A cost
      comparison of 936 primary NMSCs diagnosed in 1999/2000 at a University affiliated
      dermatology practice. Clinical data was from medical record review. 2007 Medicare
      Fee Schedule costs determined fees for surgical care. Pearson chi-square tests, t
      tests and analysis of variance compared fee differences. Linear regression
      determined independent effects of tumor and treatment characteristics on fees.
      RESULTS: Mean fees/lesion were $463 for ED&C, $1,222 for excision, and $2,085 for
      MMS (p < .001). For all treatments, primary procedure costs were highest (38%,
      45%, and 41%). Total repair fees were higher with MMS ($735) vs excisions ($197).
      Fees were higher for head and neck tumors (p < .001), H-zone tumors (p < .001),
      and tumors smaller than 10 mm in diameter (p = .04). Regression models predicted
      that the treatment fees would be $2,109 for MMS and $1,252 for excision (p <
      .001). Tumor size greater than 10 mm in diameter (added $128), tumors on the head
      and neck (added $966), and MMS (added $857 vs excision) were independently
      related to higher fees (p < .001). CONCLUSION: Even after adjusting for risk
      factors, MMS has higher fees than excision for primary NMSC. Repairs accounted
      for the majority of this difference. These fee comparisons provide a basis for
      comparative effectiveness studies of treatments for this common cancer.

PMID- 22145799
TI  - Assessment of liquid chromatography-tandem mass spectrometry approaches for the
      analysis of ceftiofur metabolites in poultry muscle.
AB  - The use of cephalosporin antibiotics in veterinary practice is likely to play an
      important role in the development of beta-lactam-resistant bacteria. To detect
      off-label cephalosporin antibiotic usage, an analytical method is needed that,
      besides the native compound, also detects their active metabolites. In this
      paper, the applicability of three approaches for the quantitative analysis of
      ceftiofur using LC-MS/MS is assessed, viz. (A) analysis of ceftiofur,
      desfuroylceftiofur and/or desfuroylceftiofur cystein disulfide, (B)
      derivatisation of ceftiofur metabolites to desfuroylceftiofur acetamide and (C)
      chemical hydrolysis using ammonia, to produce a marker compound for ceftiofur. We
      found that approach A was not suited for quantitative analysis of total ceftiofur
      concentration or for effectively detecting off-label use of ceftiofur. Approach B
      resulted in adequate quantitative results, but was considered a single compound
      method because it depends on cleavage of a thioester group, which is present in
      only a limited number of cephalosporin antibiotics. Approach C showed adequate
      quantitative results but, in contrast to approach B, it is applicable to a range
      of cephalosporin antibiotics. Therefore, it is applicable as a broad quantitative
      screening of cephalosporin compounds in poultry tissue samples to indicate off
      label use of cephalosporins in poultry breeding. Based on this study, it was
      concluded that approach C is the most suitable to detect off-label use of a range
      of cephalosporin antibiotics.

PMID- 22145800
TI  - Three-component chiral derivatizing protocols for NMR spectroscopic
      enantiodiscrimination of hydroxy acids and primary amines.
AB  - The novel three-component chiral derivatization protocols have been derived for
      (1)H and (19)F NMR spectroscopic discrimination of a series of chiral hydroxy
      acids by their coordination and self-assembly with optically active alpha
      methylbenzylamine and 2-formylphenylboronic acid. In addition, the optically pure
      (S)-mandelic acid in combination with 2-formylphenylboronic acid permits
      visualization of enantiomers of primary amines. These protocols have been
      demonstrated on enantiodiscrimination of chiral amines and hydroxy acids.

PMID- 22145801
TI  - Analysis of altered proteins related to blast crisis in chronic myeloid leukemia
      by proteomic study.
AB  - INTRODUCTION: Chromic myeloid leukemia (CML) blast crisis (BC) and imatinib (IM)
      resistance is a significant barrier to the effective treatment of the disease.
      METHODS: Expression profiles of differential proteins were identified, and new
      biomarkers or pathways related to BC in CML were screened through proteomic
      analysis. Total proteins from primary bone marrow cells of CML patients in
      chronic phase (CP) and BC were separated via two-dimensional (2D) polyacrylamide
      gel electrophoresis and then analyzed by imagemaster 5.0 software to detect
      differential protein spots which were already identified by mass spectrometry.
      Based on the variation of the whole expression profile, some key proteins were
      picked out for Western blot to confirm the accuracy of proteomics data. Moreover,
      related signal pathways involving those proteins were investigated. RESULTS: The
      result indicated that thirteen protein points between CML-CP and CML-BC were
      successfully determined. Results from Western blot of RhoA, hnRNPK, ANXA1, PSMB4,
      and LTA4H were similar to those from 2D polyacrylamide gel electrophoresis. Most
      of those proteins were involved in the proteosome pathway and the small G-protein
      pathway. CONCLUSION: A group of proteins associated with BC can be obtained and
      the result of this study might provide clues for further research.

PMID- 22145802
TI  - A citric acid-derived ligand for modular functionalization of metal oxide
      surfaces via "click" chemistry.
AB  - Citric acid is a widely used surface-modifying ligand for growth and processing
      of a variety of nanoparticles; however, the inability to easily prepare
      derivatives of this molecule has restricted the development of versatile
      chemistries for nanoparticle surface functionalization. Here, we report the
      design and synthesis of a citric acid derivative bearing an alkyne group and
      demonstrate that this molecule provides the ability to achieve stable,
      multidentate carboxylate binding to metal oxide nanoparticles, while also
      enabling subsequent multistep chemistry via the Cu(I)-catalyzed azide-alkyne
      cycloaddition (CuAAC) reaction. The broad utility of this strategy for the
      modular functionalization of metal oxide surfaces was demonstrated by its
      application in the CuAAC modification of ZnO, Fe(2)O(3), TiO(2), and WO(3)
      nanoparticles.

PMID- 22145803
TI  - In vitro studies of composite bone filler based on poly(propylene fumarate) and
      biphasic alpha-tricalcium phosphate/hydroxyapatite ceramic powder.
AB  - While many different filler materials have been applied in vertebral augmentation
      procedures, none is perfect in all biomechanical and biological characteristics.
      To minimize possible shortages, we synthesized a new biodegradable, injectable,
      and premixed composite made from poly(propylene fumarate) (PPF) and biphasic
      alpha-tricalcium phosphate (alpha-TCP)/hydroxyapatite (HAP) ceramics powder and
      evaluated the material properties of the compound in vitro. We mixed the PPF
      cross-linked by N-vinyl pyrrolidinone and biphasic alpha-TCP/HAP powder in
      different ratios with benzoyl peroxide as an initiator. The setting time and
      temperature were recorded, although they could be manipulated by modulating the
      concentrations of hydroquinone and N,N-dimethyl-p-toluidine. Degradation,
      cytocompatibility, mechanical properties, and radiopacity were analyzed after the
      composites were cured by a cylindrical shape. We also compared the study
      materials with poly(methyl methacrylate) (PMMA) and PPF with pure HAP particles.
      Results showed that lower temperature during curing process (38-44 degrees C),
      sufficient initial mechanical compressive fracture strength (61.1+/-3.7MPa), and
      gradual degradation were observed in the newly developed bone filler. Radiopacity
      in Hounsfield units was similar to PMMA as determined by computed tomography
      scan. Both pH value variation and cytotoxicity were within biological tolerable
      limits based on the biocompatibility tests. Mixtures with 70% alpha-TCP/HAP
      powder were superior to other groups. This study indicated that a composite of
      PPF and biphasic alpha-TCP/HAP powder is a promising, premixed, injectable
      biodegradable filler and that a mixture containing 70% alpha-TCP/HAP exhibits the
      best properties.

PMID- 22145804
TI  - Exercise is associated with better erectile function in men under 40 as evaluated
      by the International Index of Erectile Function.
AB  - INTRODUCTION: Studies have shown an association between erectile dysfunction and
      sedentary lifestyle in middle-aged men, with a direct correlation between
      increased physical activity and improved erectile function. Whether or not this
      relationship is present in young, healthy men has yet to be demonstrated. AIM:
      The aim of this study was to assess the association between physical activity and
      erectile function in young, healthy men. MAIN OUTCOME MEASURES: The primary end
      points for our study were: (i) differences in baseline scores of greater than one
      point per question for the International Index of Erectile Function (IIEF); (ii)
      differences in baseline scores of greater than one point per question for each
      domain of the IIEF; (iii) exercise energy expenditure; and (iv) predictors of
      dysfunction as seen on the IIEF. METHODS: The participants were men between the
      ages of 18 and 40 years old at an academic urology practice. Patients self
      administered the Paffenbarger Physical Activity Questionnaire and the IIEF.
      Patients were stratified by physical activity into two groups: a sedentary group
      (<=1,400 calories/week) and an active group (>1,400 calories/week). Men
      presenting for the primary reason of erectile dysfunction or Peyronie's disease
      were excluded. RESULTS: Seventy-eight patients had complete information in this
      study: 27 patients (34.6%) in the sedentary group (<=1,400 kcal/week) and 51
      patients (65.4%) in the active group (>1,400 kcal/week). Sedentary lifestyle was
      associated with increased dysfunction in the following domains of the IIEF:
      erectile function (44.4% vs. 21.6%, P = 0.04), orgasm function (44.4% vs. 17.7%,
      P = 0.01), intercourse satisfaction (59.3% vs. 35.3%, P = 0.04), and overall
      satisfaction (63.0% vs. 35.3%, P = 0.02). There was a trend toward more
      dysfunction in the sedentary group for total score on the IIEF (44.4% vs. 23.5%,
      P = 0.057), while sexual desire domain scores were similar in both groups (51.9%
      vs. 41.2%, P = 0.37). CONCLUSIONS: We have demonstrated that increased physical
      activity is associated with better sexual function measured by a validated
      questionnaire in a young, healthy population. Further studies are needed on the
      long-term effects of exercise, or lack thereof, on erectile function as these men
      age.

PMID- 22145805
TI  - Plasma rich in growth factors promote gingival tissue regeneration by stimulating
      fibroblast proliferation and migration and by blocking transforming growth factor
      beta1-induced myodifferentiation.
AB  - BACKGROUND: Periodontitis involves inflammation and infection of the ligaments
      and bones that support the teeth. Gingival fibroblasts are the most abundant
      cells in periodontal tissue, and they play a role in maintaining the structural
      integrity of the tissue. Plasma rich in growth factors contain a pool of proteins
      and growth factors that promote wound healing and tissue regeneration. In the
      present study, we evaluate the potential of different formulations obtained with
      this approach to stimulate several biologic processes involved in wound healing,
      including fibroblast proliferation, migration, adhesion, and the autocrine
      release of some angiogenic factors and extracellular matrix components.
      Furthermore, the ability of this technology to prevent and inhibit transforming
      growth factor beta1-induced myodifferentiation was also determined. METHODS: Cell
      proliferation was evaluated through a colorimetric assay, cell migration was
      performed on culture inserts, and cell adhesion was studied through a
      fluorescence-based method. Enzyme-linked immunosorbent assay was used to
      determine some of the biomolecules released by gingival fibroblasts. Smooth
      muscle actin expression was assessed through immunofluorescence microscopy.
      RESULTS: Results showed that plasma rich in growth factors significantly
      increased gingival fibroblast proliferation, migration, and cell adhesion on type
      I collagen matrix. In addition, it stimulated the autocrine expression of
      vascular endothelial growth factor, hepatocyte growth factor, and hyaluronic
      acid. The myofibroblast phenotype, which is characterized by expressing alpha
      smooth muscle actin, was inhibited and reverted by treating with this technology.
      CONCLUSION: These findings suggest that plasma rich in growth factors is capable
      of promoting regeneration of gingival connective tissue by stimulating some of
      the main processes involved in wound regeneration.

PMID- 22145806
TI  - The effect of internal versus external abutment connection modes on crestal bone
      changes around dental implants: a radiographic analysis.
AB  - BACKGROUND: To the best of our knowledge, the influence of external versus
      internal implant-abutment connections on crestal bone remodeling has not been
      reported. The aim of the present study is to investigate the influence of the
      abutment connection on peri-implant crestal bone levels (CBLs) using radiographic
      recordings. METHODS: Radiographic recordings from 40 single-tooth implants (20
      external and 20 internal octagonal connections; one implant/patient) in 40
      patients (15 males and 25 females; mean age: 54.3 years) were selected for
      analyses. The radiographic evaluation included the following: 1) linear bone
      change (LBC); 2) dimensional change (DC); and 3) angle between the implant and
      adjacent bone (AIB). Differences in LBC, DC, and AIB between implant placement
      and 1 year after loading for each system were evaluated using a paired t test.
      Comparison of LBC, DC, and AIB between systems at 1 year after loading was done
      using analysis of covariance. The significance level was set at P <=0.05.
      RESULTS: Radiographic CBLs (LBCs) were reduced at 1 year after loading compared
      to those at implant placement to reach statistical significance for the external
      connection (P = 0.000) but not the internal connection (P = 0.939). CBL changes
      were significantly greater for the external compared to the internal connection
      (P = 0.000). Similarly, the DC for the external connection was significantly
      greater compared to that for the internal connection (P = 0.004). CONCLUSION:
      Within the limitations of this study, the implant-abutment connection technology
      appears to have a significant impact on peri-implant CBLs, with the external
      connection paralleled by a significant reduction of CBLs.

PMID- 22145807
TI  - Angiotensin II-dependent phosphorylation at Ser11/Ser18 and Ser938 shifts the E2
      conformations of rat kidney Na+/K+-ATPase.
AB  - Kidney plasma membranes, which contain a single alpha-1 isoform of Na+/K+-ATPase,
      simultaneously contain two sub-conformations of E2P, differing in their rate of
      digoxin release in response to Na+ and ATP. Treating cells with Ang II
      (angiotensin II) somehow changes the conformation of both, because it
      differentially inhibits the rate of digoxin release. In the present study we
      tested whether Ang II regulates release by increasing phosphorylation at
      Ser11/Ser18 and Ser938. Opossum kidney cells co-expressing the AT1a receptor and
      either alpha-1.wild-type, alpha-1.S11A/S18A or alpha-1.S938A were treated with or
      without 10 nM Ang II for 5 min, increasing phosphorylation at the three sites.
      Na+/K+-ATPase was bound to digoxin-affinity columns in the presence of Na+, ATP
      and Mg2+. A solution containing 30 mM NaCl and 3 mM ATP eluted ~20% of bound
      untreated Na+/K+-ATPase (Population #1). Pre-treating cells with Ang II slowed
      the elution of Population #1 in alpha-1.wild-type and alpha-1.S938A, but not
      alpha-1.S11A/S18A cells. Another 50% of bound Na+/K+-ATPase (Population #2) was
      subsequently eluted in two phases by a solution containing 150 mM NaCl and 3 mM
      ATP. Ang II increased the initial rate and slowed the second phase in alpha
      1.wild-type, but not alpha-1.S938A, cells. Thus Ang II changes the conformation
      of two forms of EP2 via differential phosphorylation.

PMID- 22145808
TI  - Antiangiogenic activity of berberine is mediated through the downregulation of
      hypoxia-inducible factor-1, VEGF, and proinflammatory mediators.
AB  - Berberine, a naturally occurring isoquinoline alkaloid, is present in a number of
      important medicinal plants. Berberine has a wide range of biochemical and
      pharmacological effects, including anticancer effects. In this study, we
      elucidated the mechanism of antiangiogenic activity of berberine using in vivo
      and in vitro models. In vivo antiangiogenic activity was studied using B16F-10
      melanoma cells and induced capillary formation in C57BL/6 mice. Berberine, at 10
      mg/kg body weight, showed significant inhibition in tumor-directed capillary
      formation and in various proangiogenic factors, such as vascular endothelial
      growth factor (VEGF), and proinflammatory mediators, such as interleukin (IL)
      1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and granulocyte macrophage
      colony-stimulating factor (GM-CSF), which are involved in tumor angiogenesis. At
      the same time, it could also increase antitumor factors, such as IL-2 and tissue
      inhibitor metalloproteinase (TIMP) levels in the serum. Berberine could also
      inhibit endothelial motility, migration, tube formation, and vessel sprouting
      from rat aortic ring in vitro. Further, berberine inhibited various transcription
      factors involved in tumor development and angiogenesis, such as NF-KB, c-Fos,
      CREB, and ATF-2. mRNA expression levels of proangiogenic factors, such as
      cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and hypoxia
      inducible factor (HIF), were also downregulated in tumor cells after treatment
      with berberine. Drastically elevated expressions of HIF and VEGF mRNA by tumor
      cells under hypoxic conditions were also decreased after treatment with
      berberine. This result clearly demonstrates that the antiangiogenic activity of
      berberine is mainly mediated through the inhibition of various proinflammatory
      and pro-angiogenic factors and the major ones are HIF, VEGF, COX-2, NO, NF-KB,
      and proinflammatory cytokines.

PMID- 22145809
TI  - Spectrophotometric assessment of peri-implant mucosa after restoration with
      zirconia abutments veneered with fluorescent ceramic: a controlled, retrospective
      clinical study.
AB  - OBJECTIVES: The purpose of this study was to investigate the optical appearance
      of the soft tissue labial to dental implants restored with fluorescent ceramic
      veneered zircona abutments. It was hypothesized that the tested abutment design
      leads to an increased brightness in the marginal peri-implant tissue, which does
      not differ from that of natural teeth. Moreover, a reduction of the color
      difference that has been reported from other abutment materials was expected.
      MATERIALS AND METHODS: A total of 12 patients with single titanium implants in
      the maxillary anterior region were recruited. All implants (N = 12) were restored
      with zirconia abutments veneered with fluorescent ceramic and full-ceramic
      crowns. Color measurements of the peri-implant mucosa at the test sites were made
      of the facial aspect of the teeth using a Spectroshade-spectrophotometer. The
      gingiva of a contralateral or adjacent natural tooth served as a control. Color
      data (CIE-L*a*b* color coordinates) were obtained in five incremental areas of 1
      * 2 mm in both test and control sites. ?E-values were calculated from the
      DeltaL*, Deltaa* and Deltab* values for each patient. RESULTS: Data acquisition
      from the test site demonstrated lower mean values of L*, a* and b* than the
      control site. Statistical significance between the test site and control site was
      reached in the L* values only in the second of the five incremental areas (P <
      0.05, Wilcoxon test). However, discrepancies in a*- and b*-values reached a
      statistically significant difference in the incremental areas 1, 2 and 4, and in
      b* in area 5 (P < 0.05, Wilcoxon test). Medians of the ?E-values in all five
      increments were found to be higher than the clinical perceptual threshold of 3.7.
      However, considering the original data, five individual patients did not reach
      the threshold in increment 1 and 2, two in increment 3 and three in increment 4.
      None of the patients showed lower ?E-values than the perceptual threshold of 3.7
      in increment 5, which had the largest distance from the gingival margin.
      CONCLUSION: The tested abutment design leads to a peri-implant soft tissue color
      that, in the critical marginal area, in five of 12 patients did not statistically
      differ from the tissue of the gingiva of natural teeth. Particularly, the
      brightness of the peri-implant soft-tissue seemed to be more adapted to the
      natural situation using a fluorescent abutment design.

PMID- 22145811
TI  - What is causing biomagnification of persistent hydrophobic organic chemicals in
      the aquatic environment?

PMID- 22145810
TI  - Endurance exercise intensity determination in the rehabilitation of coronary
      artery disease patients: a critical re-appraisal of current evidence.
AB  - In the care of coronary artery disease (CAD) patients, the benefits of exercise
      therapy are generally established. Even though the selected endurance exercise
      intensity might affect medical safety, therapy adherence and effectiveness in the
      rehabilitation of CAD patients in how to determine endurance exercise intensity
      properly remains difficult. The aim of this review is to describe the available
      methods for endurance exercise intensity determination in the rehabilitation of
      CAD patients, accompanied with their (dis)advantages, validity and
      reproducibility. In general, endurance exercise intensity can objectively be
      determined in CAD patients by calculating a fraction of maximal exercise
      tolerance and/or determining ventilatory threshold after execution of a
      cardiopulmonary exercise test with ergospirometry. This can be translated to a
      corresponding training heart rate (HR) or workload. In the absence of
      ergospirometry equipment, target exercise HR can be calculated directly by
      different ways (fraction of maximal HR and/or Karvonen formula), and/or anaerobic
      threshold can be determined. However, the use of HR for determining exercise
      intensity during training sessions seems complicated, because many
      factors/conditions affect the HR. In this regard, proper standardization of the
      exercise sessions, as well as exercise testing, might be required to improve the
      accuracy of exercise intensity determination. Alternatively, subjective methods
      for the determination of endurance exercise intensity in CAD patients, such as
      the Borg ratings of perceived exertion and the talk test, have been developed.
      However, these methods lack proper validity and reliability to determine
      endurance exercise intensity in CAD patients. In conclusion, a practical and
      systematic approach for the determination of endurance exercise intensity in CAD
      patients is presented in this article.

PMID- 22145812
TI  - Synthesis, characterization, and DNA binding properties of ruthenium(II)
      complexes containing the redox active ligand benzo[i]dipyrido[3,2-a:2',3'
      c]phenazine-11,16-quinone.
AB  - Synthetic methods toward ruthenium(II) complexes incorporating the
      benzo[i]dipyrido[3,2-a:2',3'-c]phenazine-11,16-quinone ligand, qdppn, are
      reported. In several cases, it was found that complexes containing coordinated
      benzo[i]dipyrido[3,2-a:2',3'-c]phenazine, dppn, could be chemically or
      photochemically oxidized to their qdppn analogues. Since this method was not
      possible in all the cases, a new, higher yielding, convenient synthesis of qdppn
      was developed. The crystal structure of the complex [Ru(phen)(2)(qppn)](PF(6))(2)
      (phen = 1,10-phenanthroline) which was synthesized from free qdppn reveals that a
      combination of pi-pi stacking between coordinated phen and qdppn units, as well
      as anion-ligand hydrogen bonding, define large hexagonal channels which are
      occupied by anions and solvent molecules. Electrochemical and photophysical
      studies reveal that the new qdppn-based complexes are not luminescent and, in
      contrast to their dppn analogues, they are also poor singlet oxygen sensitizers.
      Time-resolved studies and density functional theory (DFT) calculations indicate
      that optical properties of the new complexes are due to a short-lived charge
      separated state involving the quinone moiety of qdppn. The DNA binding properties
      of the new complexes have also been investigated. It was found that they are
      intercalators, displaying binding affinities which are comparable to their dppn
      analogues.

PMID- 22145814
TI  - Decreased activation and increased lateralization in brain functioning for
      selective attention and response inhibition in adolescents with spina bifida.
AB  - We used functional magnetic resonance imaging to evaluate functional activity in
      the brain of adolescents with spina bifida when performing selective attention
      and response inhibition tasks. We then compared the results to that of age
      matched controls. Our results showed that adolescents with spina bifida had
      decreased frontal and superior parietal activation and more apparently low
      involvement of left brain hemisphere during these tasks. Our results indicated
      activation deficits and possibly abnormal functional organization in adolescents
      with spina bifida and associated pathologies such as hydrocephalus.

PMID- 22145813
TI  - Inhibition of HIV-1 infection by TNPO3 depletion is determined by capsid and
      detectable after viral cDNA enters the nucleus.
AB  - BACKGROUND: HIV-1 infects non-dividing cells. This implies that the virus
      traverses the nuclear pore before it integrates into chromosomal DNA. Recent
      studies demonstrated that TNPO3 is required for full infectivity of HIV-1. The
      fact that TNPO3 is a karyopherin suggests that it acts by directly promoting
      nuclear entry of HIV-1. Some studies support this hypothesis, while others have
      failed to do so. Additionally, some studies suggest that TNPO3 acts via HIV-1
      Integrase (IN), and others indicate that it acts via capsid (CA). RESULTS: To
      shed light on the mechanism by which TNPO3 contributes to HIV-1 infection we
      engineered a panel of twenty-seven single-cycle HIV-1 vectors each bearing a
      different CA mutation and characterized them for the ability to transduce cells
      in which TNPO3 had been knocked down (KD). Fourteen CA mutants were relatively
      TNPO3-independent, as compared to wild-type (WT) HIV-1. Two mutants were more
      TNPO3-dependent than the WT, and eleven mutants were actually inhibited by TNPO3.
      The efficiency of the synthesis of viral cDNA, 2-LTR circles, and proviral DNA
      was then assessed for WT HIV-1 and three select CA mutants. Controls included
      rescue of TNPO3 KD with non-targetable coding sequence, RT- and IN- mutant
      viruses, and pharmacologic inhibitors of RT and IN. TNPO3 KD blocked transduction
      and establishment of proviral DNA by wild-type HIV-1 with no significant effect
      on the level of 2-LTR circles. PCR results were confirmed by achieving TNPO3 KD
      using two different methodologies (lentiviral vector and siRNA oligonucleotide
      transfection); by challenging three different cell types; by using two different
      challenge viruses, each necessitating different sets of PCR primers; and by
      pseudotyping virus with VSV G or using HIV-1 Env. CONCLUSION: TNPO3 promotes HIV
      1 infectivity at a step in the virus life cycle that is detectable after the
      preintegration complex arrives in the nucleus and CA is the viral determinant for
      TNPO3 dependence.

PMID- 22145815
TI  - STAT3 signaling after traumatic brain injury.
AB  - Astrocytes respond to trauma by stimulating inflammatory signaling. In studies of
      cerebral ischemia and spinal cord injury, astrocytic signaling is mediated by the
      cytokine receptor glycoprotein 130 (gp130) and Janus kinase (Jak) which
      phosphorylates the transcription factor signal transducer and activator of
      transcription-3 (STAT3). To determine if STAT3 is activated after traumatic brain
      injury (TBI), adult male Sprague-Dawley rats received moderate parasagittal fluid
      percussion brain injury or sham surgery, and then the ipsilateral cortex and
      hippocampus were analyzed at various post-traumatic time periods for up to 7
      days. Western blot analyses indicated that STAT3 phosphorylation significantly
      increased at 30 min and lasted for 24 h post-TBI. A significant increase in gp130
      and Jak2 phosphorylation was also observed. Confocal microscopy revealed that
      STAT3 was localized primarily within astrocytic nuclei. At 6 and 24 h post-TBI,
      there was also an increased expression of STAT3 pathway-related genes: suppressor
      of cytokine signaling 3, nitric oxide synthase 2, colony stimulating factor 2
      receptor beta, oncostatin M, matrix metalloproteinase 3, cyclin-dependent kinase
      inhibitor 1A, CCAAT/enhancer-binding protein beta, interleukin-2 receptor gamma,
      interleukin-4 receptor alpha, and alpha-2-macroglobulin. These results clarify
      some of the signaling pathways operative in astrocytes after TBI and demonstrate
      that the gp130-Jak2-STAT3 signaling pathway is activated after TBI in astrocytes.

PMID- 22145816
TI  - Local inflammation influences oestrogen metabolism in prostatic tissue.
AB  - What's known on the subject? and What does the study add? The role of oestrogen
      in prostatic inflammation has been extensively shown. The catechol oestrogens are
      known to be more potent oestrogenic moieties that not only aggravate the
      inflammatory response in situ, but are also believed to have oxidative stress and
      genotoxic effects. The present study highlights a significant role of
      inflammation in oestrogen metabolism and, particularly, in generating 'bad'
      oestrogen metabolites. This finding may pave the way for new therapeutic methods
      for the treatment and/or prevention of prostate diseases. OBJECTIVE: * To
      investigate the impact of experimentally induced inflammation on oestrogen
      metabolism in rat prostate. MATERIALS AND METHODS: * Prostatitis was induced in
      normal and oestrogen-treated male rats by injecting 2% carrageenan solution into
      the ventral prostate. After 48 h, the rats were killed and the ventral prostate
      was collected. * Prostatic inflammation and proliferation were confirmed by gross
      visual evidence, histology and elevated tumour necrosis factor-alpha,
      prostaglandin E(2) and cyclin-D(1) . * Expression of oestrogen-metabolizing
      enzymes was assessed using capillary electrophoresis, and oestrogen metabolites
      within prostate tissue were assayed using liquid chromatography mass
      spectrometry. RESULTS: * Animals exposed to carrageenan insult combined with
      oestrogen treatment showed the most prominent inflammatory and proliferative
      response. * Treatment of animals with oestrogen alone induced moderate
      inflammation and proliferation. * Oestrogen-metabolizing enzymes were
      overexpressed in animals with experimental prostatitis with sequential
      accumulation of catechol oestrogens within prostatic tissues. * Oestrogen
      receptor-alpha was underexpressed in the prostatitis with oestrogen group, while
      oestrogen receptor-beta was overexpressed. CONCLUSIONS: * The present work
      provides experimental evidence that local inflammation enhances oestrogen
      synthesis and directs oestrogen metabolism to generate catechol oestrogens within
      prostatic tissues. * This may contribute, at least partly, to enhanced prostatic
      cell proliferation.

PMID- 22145817
TI  - 2B or not 2B? Masquerading as von Willebrand disease?

PMID- 22145818
TI  - Effect of pulsed electric field on the rheological and colour properties of soy
      milk.
AB  - The effects of pulsed electric field (PEF) treatments on rheological and colour
      properties of soy milk were evaluated. Flow behaviour, viscosity and rheological
      parameters of PEF-treated soy milk were monitored using a controlled stress
      rheometer. For PEF treatments, electric field intensity of 18, 20 and 22 kV cm(
      1) and number of pulses of 25, 50, 75 and 100 were used. For the measurements of
      rheological properties of soy milk shear rates between 0 and 200 s(-1) was used.
      The rheological behaviour of control and the PEF-treated soy milk were described
      using a power law model. The PEF treatments affected the rheological properties
      of soy milk. Apparent viscosity of soy milk increased from 6.62 to 7.46 (10(-3)
      Pa s) with increase in electric field intensity from 18 to 22 kV cm(-1) and
      increase in the number of pulses from 0 to 100. The consistency index (K) of soy
      milk also changed with PEF treatments. Lightness (L*), red/greenness (a*) and
      yellowness/blueness (b*) of soy milk were affected by PEF treatments.

PMID- 22145820
TI  - Risk of first venous thromboembolism in and around pregnancy: a population-based
      cohort study.
AB  - Knowledge of the absolute and relative risk of venous thromboembolism (VTE) in
      and around pregnancy would be crucial in identifying when to commence and cease
      thromboprophylaxis in women who would benefit from such intervention. We
      addressed this hypothesis using a large prospective primary care database from
      the United Kingdom, containing details on 972683 women aged 15-44years between
      1987 and 2004. Risks of a first VTE during antepartum, postpartum and outside of
      pregnancy were compared using Poisson regression. The rate of VTE during the
      third trimester antepartum was six times higher than time outside pregnancy
      [Incidence Rate Ratio (IRR)=6.1; 95% confidence interval, 4.7-7.9]. In contrast,
      both the first (IRR=1.6) and second (IRR=2.1) trimesters conferred little
      increase in risk. The first 6weeks postpartum was associated with a 22-fold
      increase in risk, with the peak occurring in the first 3weeks. Increased age was
      found to be associated with VTE during postpartum and outside of pregnancy, but
      not during antepartum. Our findings of a notably raised risk of VTE persisting
      for 3 weeks postpartum and of a raised antepartum risk constrained to the third
      trimester have implications for modifying the current recommendations for VTE
      prophylaxis in pregnancy and the puerperium.

PMID- 22145819
TI  - Chemical composition and enzymatic digestibility of sugarcane clones selected for
      varied lignin content.
AB  - BACKGROUND: The recalcitrance of lignocellulosic materials is a major limitation
      for their conversion into fermentable sugars. Lignin depletion in new cultivars
      or transgenic plants has been identified as a way to diminish this recalcitrance.
      In this study, we assessed the success of a sugarcane breeding program in
      selecting sugarcane plants with low lignin content, and report the chemical
      composition and agronomic characteristics of eleven experimental hybrids and two
      reference samples. The enzymatic digestion of untreated and chemically
      delignified samples was evaluated to advance the performance of the sugarcane
      residue (bagasse) in cellulosic-ethanol production processes. RESULTS: The ranges
      for the percentages of glucan, hemicellulose, lignin, and extractive (based on
      oven-dry biomass) of the experimental hybrids and reference samples were 38% to
      43%, 25% to 32%, 17% to 24%, and 1.6% to 7.5%, respectively. The samples with the
      smallest amounts of lignin did not produce the largest amounts of total
      polysaccharides. Instead, a variable increase in the mass of a number of
      components, including extractives, seemed to compensate for the reduction in
      lignin content. Hydroxycinnamic acids accounted for a significant part of the
      aromatic compounds in the samples, with p-coumaric acid predominating, whereas
      ferulic acid was present only in low amounts. Hydroxycinnamic acids with ester
      linkage to the hemicelluloses varied from 2.3% to 3.6%. The percentage of total
      hydroxycinnamic acids (including the fraction linked to lignin through ether
      linkages) varied from 5.0% to 9.2%, and correlated to some extent with the lignin
      content. These clones released up to 31% of glucose after 72 hours of digestion
      with commercial cellulases, whereas chemically delignified samples led to
      cellulose conversion values of more than 80%. However, plants with lower lignin
      content required less delignification to reach higher efficiencies of cellulose
      conversion during the enzymatic treatment. CONCLUSION: Some of the experimental
      sugarcane hybrids did have the combined characteristics of high biomass and high
      sucrose production with low lignin content. Conversion of glucan to glucose by
      commercial cellulases was increased in the samples with low lignin content.
      Chemical delignification further increased the cellulose conversion to values of
      more than 80%. Thus, plants with lower lignin content required less
      delignification to reach higher efficiencies of cellulose conversion during the
      enzymatic treatment.

PMID- 22145821
TI  - Dehydroepiandrosterone sulphate: action and mechanism in the brain.
AB  - Dehydroepiandrosterone sulphate (DHEAS) is synthesised from
      dehydroepiandrosterone by the enzyme sulphotransferase. DHEAS is one of the most
      important neurosteroids in the brain. The concentration of DHEAS in the brain is
      sometimes higher than peripheral system. At the cellular level, DHEAS has been
      shown to modulate a variety of synaptic transmission, including cholinergic,
      GABAergic dopaminergic and glutamatergic synaptic transmission. In addition to
      the effect on the release of a number of neurotransmitters, DHEAS could also
      modulate the activity of postsynaptic receptors. DHEAS has been found to have
      multiple important effects on brain functions, such as memory enhancing,
      antidepressant and anxiolytic effects, and may have relationships with many brain
      diseases.

PMID- 22145822
TI  - Primary care providers' views regarding assessing and treating suicidal patients.
AB  - Primary care providers (PCPs) usually do not explore patient suicidality during
      routine visits. Factors that predict PCP attitudes toward the assessment and
      treatment of suicidality were examined via an online survey of 195 practicing
      PCPs affiliated with medical schools in the United States. PCPs who perceived
      themselves as competent to work with suicidal patients were more willing to
      assess and more willing to treat suicidal patients, with the perception of
      competency fully explaining the relationship between training and willingness to
      treat. Female gender predicted lower self-perceived competency, while in-office
      access to professional mental health (MH) consultation predicted greater self
      perceived competency. Higher self-perceived general competence predicted lower
      subjective valuation of access to MH consultation. Multiple linear regression
      analysis indicated a three-way interaction between training, gender, and
      valuation of MH consultation as predictors of perceived competency, with training
      generally being associated with greater perceived competency to treat
      suicidality. Relative to their male counterparts, female PCPs have lower
      confidence in assessing and treating suicidality. Perceived competence in risk
      assessment should be given more attention in medical training because of its role
      in PCPs' willingness to treat suicidality.

PMID- 22145823
TI  - The impact of the nature of relationships on perceived burdensomeness and suicide
      ideation in a community sample of older adults.
AB  - Older adults die by suicide at very high rates, and previous research indicates
      that perceived burdensomeness may contribute to deaths by suicide. In this study,
      the impact of the nature of relationships on perceived burdensomeness and suicide
      ideation was examined. Results indicated that older adults' perceptions of burden
      on younger generations were associated with greater overall perceived
      burdensomeness and suicide ideation when compared to the older adults' own or
      older generations. Thus, clinicians should examine general perceived
      burdensomeness as well as the types of relationships the older adult perceives
      himself or herself to be a burden on.

PMID- 22145824
TI  - Age, gender, and reasons for living among Australian adults.
AB  - Reasons for living have been identified as protective factors in relation to
      suicide, and much research has documented gender differences in reasons for
      living. In contrast, little research has investigated age differences in reasons
      for living. In the current study, the relationship of age to reasons for living
      was investigated, as was whether age and gender interact to influence reasons for
      living. A community sample of Australian adults (N = 970) aged 18 to 95 years (M
      = 48.40, SD = 20.85) completed the Reasons for Living Inventory. Results for the
      main effects indicated that being female was associated with higher total, child
      related concerns and fear of suicide (FS) scores, whereas increasing age was
      associated with higher total, responsibility to family (RF), FS, and moral
      objections scores. Age and gender interacted to influence RF, FS, and fear of
      social disapproval. For each of these reasons for living, increasing age was
      associated with higher scores for men; however, there was no association between
      age and these reasons for living scores among women. Overall, the results
      indicate that the influence of age, gender, or the combination of the two varies
      according to the reason for living being investigated.

PMID- 22145825
TI  - Nonlinear dynamics: theoretical perspectives and application to suicidology.
AB  - Despite decades of research, the prediction of suicidal behavior remains limited.
      As a result, searching for more specific risk factors and testing their
      predictive power are central in suicidology. This strategy may be of limited
      value because it assumes linearity to the suicidal process that is most likely
      nonlinear by nature and which can be more adequately described and analyzed with
      nonlinear dynamics. The goal of moving nonlinear dynamics from theory to practice
      and to real-world phenomena can now be realized with Internet-based monitoring
      systems such as the Synergetic Navigation System.

PMID- 22145826
TI  - The association between bankruptcy and hospital-presenting attempted suicide: a
      record linkage study.
AB  - The associations between admissions to an emergency department following
      attempted suicide and personal bankruptcy in the preceding and subsequent 2 years
      were evaluated. Records from a level 1 trauma center (June 1993-December 2002) in
      Seattle, WA, were linked with case files from the local U.S. District Bankruptcy
      Court (June 1991 onward). Univariable and multivariable logistic regression
      models were used to examine the risk of bankruptcy in (i) the 2 years after and
      (ii) the 2 years before a suicide attempt using a violent method, compared to
      patients admitted for any other reason. After adjusting for several confounders,
      patients who had attempted suicide were more likely than other patients to
      experience bankruptcy in the following 2 years (OR = 2.10, 95% CIs: 1.29, 3.42).
      A somewhat weaker association was seen with bankruptcy in the preceding 2 years
      (OR = 1.68, 95% CIs 1.06; 2.67). Attempted suicide is therefore associated with
      bankruptcy in the preceding and following 2 years. Changes to legislation,
      improved mental health counselling for those in financial difficulty, and
      provision of financial advice to those admitted to hospital following a suicide
      attempt may reduce future cases of serious self-harm and completed suicide.

PMID- 22145827
TI  - Suicide method runs in families: a birth certificate cohort study of adolescent
      suicide in Taiwan.
AB  - Suicide method used by adolescents was examined to determine if it was the same
      as that employed by their suicidal parents. Six hundred eighty adolescents
      completed suicide between 1997 and 2007, of whom 12 had parents who had
      previously died by suicide. The suicide method used by these adolescents was
      compared with that employed by their suicidal parent and that of a matched peer
      control adolescent with no exposure to parental suicide and living in the same
      area. In 10 of the 12 suicidal parent-adolescent dyads, the same suicide method
      was employed by parent and adolescent. Of seven adolescents whose age at parental
      suicide was 15 years or above, six used the same suicide method as their suicidal
      parent had. On the contrary, of 12 exposure-nonexposure suicidal adolescent
      dyads, the same method was used in only four. Adolescents exposed to parental
      suicide are more likely to use the suicide method employed by their suicidal
      parents than the method used by adolescent peers with no exposure to parental
      suicide.

PMID- 22145828
TI  - Design and study protocol of the maternal smoking cessation during pregnancy
      study, (M-SCOPE).
AB  - BACKGROUND: Maternal smoking is the most significant cause of preventable
      complications during pregnancy, with smoking cessation during pregnancy shown to
      increase birth weight and reduce preterm birth among pregnant women who quit
      smoking. Taking into account the fact that the number of women who smoke in
      Greece has increased steadily throughout the previous decade and that the
      prevalence of smoking among Greek females is one of the highest in the world,
      smoking cessation should be a top priority among Greek health care professionals.
      METHODS/DESIGN: The Maternal Smoking Cessation during Pregnancy Study (M-SCOPE),
      is a Randomized Control Trial (RCT) that aims to test whether offering Greek
      pregnant smokers a high intensity intervention increases smoking cessation during
      the third trimester of pregnancy, when compared to a low intensity intervention.
      Prospective participants will be pregnant smokers of more than 5 cigarettes per
      week, recruited up to the second trimester of pregnancy. Urine samples for
      biomarker analysis of cotinine will be collected at three time points: at
      baseline, at around the 32nd week of gestation and at six months post partum. The
      control group/low intensity intervention will include: brief advice for 5 minutes
      and a short leaflet, while the experimental group/intensive intervention will
      include: 30 minutes of individualized cognitive-behavioural intervention provided
      by a trained health professional and a self-help manual especially tailored for
      smoking cessation during pregnancy, while counselling will be based on the ''5
      As.'' After childbirth, the infants' birth weight, gestational age and any other
      health related complications during pregnancy will be recorded. A six months post
      partum a follow up will be performed in order to re-assess the quitters smoking
      status. DISCUSSION: If offering pregnant smokers a high intensity intervention
      for smoking cessation increases the rate of smoking cessation in comparison to a
      usual care low intensity intervention in Greek pregnant smokers, such a scheme if
      beneficial could be implemented successfully within clinical practice in Greece.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01210118.

PMID- 22145829
TI  - Immunoglobulin G levels can predict non-diabetic renal disease in patients with
      type 2 diabetes mellitus.
AB  - BACKGROUND: Proteinuria in patients with diabetes mellitus (DM) is sometimes
      caused by glomerular diseases other than diabetic nephropathy. In patients with
      type 2 DM (T2DM), specific predictors for non-diabetic renal disease (NDRD) are
      needed in addition to the traditional indicators for renal biopsy. METHODS: From
      1 January 2000 to 31 March 2011, we retrospectively enrolled 54 T2DM patients
      with proteinuria who had undergone renal biopsies into the present study.
      Associations between NDRD and 20 potential biomarkers, including serum levels of
      Igs and proteins associated with kidney function, and urinary protein and red
      blood cell levels, and hepatitis virus carrier status, were analyzed by
      multivariate logistic regression. RESULTS: Multivariate logistic regression
      showed that reduced serum IgG (odds ratio [OR] 0.997; P = 0.006; 95% confidence
      interval [CI] 0.94-0.998) and creatinine (Cr; OR 0.587; P = 0.014; 95% CI 0.348
      0.897) were predictors of NDRD. The area under the receiver operating
      characteristic curve (AUC(ROC) ) confirmed the good discriminatory power of IgG
      (AUC(ROC) 0.857 +/- 0.058; 95% CI 0.744-0.970; P < 0.001) and Cr (AUC(ROC) 0.838
      +/- 0.054; 95% CI 0.732-0.943; P < 0.001). The IgG level below which the risk for
      NDRD increased, as calculated by obtaining the best Youden index, was 919.5 mg/dL
      (sensitivity 91.7%; specificity 83.3%), and the corresponding Cr level was 4.1
      mg/dL (sensitivity 58.3%; specificity 96.7%). CONCLUSION: Serum IgG levels <919.5
      mg/dL and serum Cr levels <4.1 mg/dL are associated with NDRD in T2DM patients.

PMID- 22145830
TI  - Curcuminoids promote neurite outgrowth in PC12 cells through MAPK/ERK- and PKC
      dependent pathways.
AB  - Curcuminoids, the predominant polyphenolic compounds in the rhizome of Curcuma
      longa Linn., consist of curcumin, demethoxycurcumin (DMC), and
      bisdemethoxycurcumin (BDMC). They exhibit multiple desirable characteristics for
      a neuroprotective agent including antioxidant, anti-inflammatory, and antiamyloid
      activities. In this work, we report the first investigation of the neurotrophic
      action and mechanism of curcuminoids in PC12 cells, which respond to nerve growth
      factor (NGF) and therefore serve as a model system for primary neuronal cells.
      The percentages of neurite-bearing cells for those treated with 20 MUM curcumin,
      DMC, and BDMC for 72 h reached 21.6 +/- 2.0%, 16.3 +/- 2.4%, and 19.9 +/- 2.5%,
      respectively, and were significantly higher than that of the negative control
      (2.0 +/- 0.3%, p < 0.05). In parallel, increased expression of the neuronal
      differentiation markers, growth-associated protein-43 (GAP-43), and neurofilament
      L (NF-L) was found in curcuminoid-treated cells. All three curcuminoids (20 MUM)
      activated extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein
      kinase C (PKC) signalings, and inhibition of these kinases with the respective
      pharmacological inhibitors effectively attenuated curcuminoid-induced neurite
      outgrowth. Furthermore, our results show that both curcumin and DMC, but not
      BDMC, induced phosphorylation of cAMP response element-binding protein (CREB) and
      CRE-reporter gene activity significantly (p < 0.05). These inductions were
      markedly attenuated by the addition of MEK/ERK or PKC inhibitor; as a
      consequence, ERK- and PKC-dependent pathways may be involved in curcuminoid
      mediated neuritogenesis in PC12 cells. Moreover, activation of CREB coupling with
      CRE-dependent gene transcription may play a vital role for curcumin- or DMC
      induced PC12 differentiation.

PMID- 22145831
TI  - Copper-catalyzed direct C-H oxidative trifluoromethylation of heteroarenes.
AB  - This article describes the copper-catalyzed oxidative trifluoromethylation of
      heteroarenes and highly electron-deficient arenes with CF(3)SiMe(3) through
      direct C-H activation. In the presence of catalyst Cu(OAc)(2), ligand 1,10
      phenanthroline and cobases tert-BuONa/NaOAc, oxidative trifluoromethylation of
      1,3,4-oxadiazoles with CF(3)SiMe(3) proceeded smoothly using either air or di
      tert-butyl peroxide as an oxidant to give the corresponding trifluoromethylated
      1,3,4-oxadiazoles in high yields. Di-tert-butyl peroxide was chosen as the
      suitable oxidant for oxidative trifluoromethylation of 1,3-azoles and
      perfluoroarenes. Cu(OH)(2) and Ag(2)CO(3) were the best catalyst and oxidant for
      direct oxidative trifluoromethyaltion of indoles. The optimum reaction conditions
      enable oxidative trifluoromethylation of a range of heteroarenes that bear
      numerous functional groups. The prepared trifluoromethylated heteroarenes are of
      importance in the areas of pharmaceuticals and agrochemicals. The preliminary
      mechanistic studies of these oxidative trifluoromethylations are also reported.

PMID- 22145832
TI  - Tissue engineering for penile surgery: comparative study of noncellular and cell
      seeded synthetic grafts for tunica albuginea replacement.
AB  - INTRODUCTION: Surgical treatment outcomes in Peyronie's disease remain
      controversial because of high rates of recurrence. AIM: The aim of this study was
      to engineer in vitro a new type of tunica albuginea (TA) autologous graft
      obtained by culture of autologous fibroblast on a polyglycolic acid (PGA)
      scaffold. This engineering graft was compared with PGA with morphological and
      functional outcomes for TA replacement, 4 months after graft upon corpus
      cavernosum in a rat model. METHODS: Thirty-nine Sprague Dawley adult male rats
      were divided into four groups: (i) control group (C) with resection and resuture
      of a 5 mm long and 2 mm large piece of original TA; (ii) PGA scaffold group (P)
      with the same resection of TA and suture of PGA scaffold; (iii) autologous
      fibroblast-seeded on PGA scaffold graft after resection of the same piece of TA
      (F + P); and (iv) sham group for functional and histological comparison. MAIN
      OUTCOME MEASURE: The main outcome measure was assessment of graft size variation
      at 4 months and comparison between the three test groups. The secondary objective
      is assessment of erectile function by measuring erectile response to cavernous
      nerve electrical stimulation in each group. RESULTS: At 4 months, there was a
      significant difference in graft area retraction between the groups (P = 0.0081)
      with higher retraction in P group vs. in C or F + P groups. Erectile response to
      cavernous nerve stimulation significantly differed between the groups and was
      sham equivalent to C equivalent to F + P superior to P group. CONCLUSIONS: This
      study provides experimental evidence for the feasibility and the functionality of
      fibroblast-seeded scaffold compared with acellular graft for TA replacement.

PMID- 22145833
TI  - PAMAM dendrimer-induced aggregation of 5(6)-carboxyfluorescein.
AB  - The binding of the fluorescent polyanionic probe 5(6)-carboxyfluorescein (CF) to
      various generations of dendrimers (G3-G7) was studied in buffered aqueous media
      by absorbance and fluorescence spectroscopy and by isothermal titration
      calorimetry (ITC). Absorbance, fluorescence, and fluorescence anisotropy data
      were collected concurrently by using a multiwell plate format. Because ITC does
      not depend on the presence of a chromophore/fluorophore for measurement, it
      allowed the exploration of concentration ratios otherwise unattainable in the
      spectroscopy experiments. Qualitative dendrimer generational trends were observed
      and found to be consistent with dendrimer size and charge. However, a number of
      significant anomalies were found in the spectroscopic titration profiles, which
      led us to propose a binding model comprising multiple, concurrent binding
      regimes. The predictive value of the model was ascertained by construction of a
      binding simulation, which was consistent with the experimental results. Finally,
      ITC results afforded insights into the fundamental thermodynamic properties of
      the binding process along with trends found across dendrimer generations.
      Thermodynamic data were found to be in accordance with the proposed model.

PMID- 22145834
TI  - Faster, safer and more accurate: 'Flash' computed tomography.

PMID- 22145836
TI  - Teaching medical device design using design control.
AB  - The design of medical devices requires an understanding of a large number of
      factors, many of which are difficult to teach in the traditional educational
      format. This subject benefits from using a challenge-based learning approach,
      which provides focused design challenges requiring students to understand
      important factors in the context of a specific device. A course was designed at
      San Diego State University (CA, USA) that applied challenge-based learning
      through in-depth design challenges in cardiovascular and orthopedic medicine, and
      provided an immersive field, needs-finding experience to increase student
      engagement in the process of knowledge acquisition. The principles of US FDA
      'design control' were used to structure the students' problem-solving approach,
      and provide a format for the design documentation, which was the basis of
      grading. Students utilized a combination of lecture materials, industry guest
      expertise, texts and readings, and internet-based searches to develop their
      understanding of the problem and design their solutions. The course was
      successful in providing a greatly increased knowledge base and competence of
      medical device design than students possessed upon entering the course.

PMID- 22145837
TI  - Transapical access: current status and future directions.
AB  - With the rapid evolution of transcatheter aortic valve implantation over the past
      few years, transapical access has evolved to be a routine approach for the
      implantation of transcatheter aortic valve prostheses. The approach itself has
      demonstrated feasibility, safety and reproducibility associated with low
      complication rates. As the access allows for relatively large profile devices and
      owing to the short anatomical distance to both the mitral and the aortic valve,
      the apical approach facilitates a wide range of interventions. Thus, minimally
      invasive transapical access can be considered as a versatile platform for the
      development of new transcatheter aortic or mitral devices.

PMID- 22145838
TI  - Dual-mobility bearings: a review of the literature.
AB  - Dislocation after total hip arthroplasty remains a major problem and hip
      instability is the most common reason for revision. These complications are
      costly to both patients and the healthcare system, and efforts to reduce them
      have had varied degrees of success. Although there are well documented patient
      and surgical risk factors for dislocation, the typical surgical solutions offered
      (constrained liners, large femoral heads) have the drawbacks of reduced range-of
      motion and high rates of revision. Dual-mobility prostheses (unconstrained
      tripolar prostheses) are hip design solutions to dislocation that aim to provide
      a greater stability with an increased range-of-motion, along with potentially
      reduced wear. The mean overall dislocation rate from multiple combined studies
      using dual-mobility prostheses was 0.1% for primary total hip arthroplasty and
      3.5% for revisions, compared with 2-7% for standard primary total hip
      arthroplasties and up to 16% for revisions. Dual-mobility prostheses offer a
      viable option for treating recurrent dislocation as well as for primary and
      revision arthroplasty.

PMID- 22145839
TI  - Bionic vision: system architectures: a review.
AB  - The concept of an electronic visual prosthesis has been investigated since the
      early 20th century. While the first generation of long-term implantable devices
      were defined by the turn of the millennium, the greatest progress has been
      achieved in the past decade. This review describes the current state of the art
      of visual prosthesis investigated by more than two dozen active groups in this
      field of research. The focus is on technological solutions in regard to long-term
      safety of materials, electrode-tissue interfaces and encapsulation technologies.
      Furthermore, we critically assess the maximum number of stimulating electrodes
      each technological approach is likely to provide.

PMID- 22145840
TI  - Miniaturization of left ventricular assist devices: the ongoing trend.
AB  - The shortage of appropriate donor hearts and the expanding pool of patients
      waiting for a heart transplantation have led to growing interest in alternative
      strategies, particularly in mechanical circulatory support. With expanding
      clinical experience and continued technical advances, continuous-flow pumps are
      evolving from bridge to transplantation to destination therapy for advanced heart
      failure. This review describes the clinical use and outcome of currently
      available miniaturized left ventricular assist devices (LVADs). It provides an
      outlook of the ongoing process of the miniaturization of LVADs, new concepts of
      partial support and, furthermore, it commentates on the current challenges with
      LVADs and the 5-year perspective.

PMID- 22145841
TI  - Biophysics and clinical utility of irrigated-tip radiofrequency catheter
      ablation.
AB  - Catheter ablation by radiofrequency (RF) energy has successfully eliminated
      cardiac tachyarrhythmias. RF ablation lesions are created by thermal energy.
      Electrode catheters with 4-mm-tips have been adequate to ablate arrhythmias
      located near the endocardium; however, the 4-mm-tip electrode does not readily
      ablate deeper tachyarrhythmia substrate. With 8- and 10-mm-tip RF electrodes,
      ablation lesions were larger; yet, these catheters are associated with increased
      risk for coagulum, char and thrombus formation, as well as myocardial steam
      rupture. Cooled-tip catheter technology was designed to cool the electrode tip,
      prevent excessive temperatures at the electrode tip-tissue interface, and thus
      allow continued delivery of RF current into the surrounding tissue. This ablation
      system creates larger and deeper ablation lesions and minimizes steam pops and
      thrombus formation. The purpose of this article is to review cooled-tip RF
      ablation biophysics and outcomes of clinical studies as well as to discuss future
      technological improvements.

PMID- 22145843
TI  - Below-the-knee drug-eluting stents and drug-coated balloons.
AB  - Endovascular procedures have evolved to the mainstream treatment of choice for
      revascularization of infrapopliteal obstructive disease, especially in patients
      suffering from critical limb ischemia and multiple comorbidities. However,
      standard balloon angioplasty is limited by the potential of a suboptimal acute
      outcome due to elastic recoil and/or flow-limiting dissection, followed by
      neointimal hyperplasia and progressive vascular restenosis even in the case of
      bare-metal stent use. Drug-eluting stents and drug-coated balloons are emerging
      endovascular technologies with the promise of significant inhibition of vessel
      restenosis and improved clinical outcomes. The current review outlines the drug
      eluting properties of those instruments and summarizes the currently available
      clinical data. The authors critically appraise the current status and also
      provide a glimpse of the near future of endovascular below-the-knee treatments.

PMID- 22145842
TI  - Transcranial near-infrared laser therapy applied to promote clinical recovery in
      acute and chronic neurodegenerative diseases.
AB  - One of the most promising methods to treat neurodegeneration is noninvasive
      transcranial near-infrared laser therapy (NILT), which appears to promote acute
      neuroprotection by stimulating mitochondrial function, thereby increasing
      cellular energy production. NILT may also promote chronic neuronal function
      restoration via trophic factor-mediated plasticity changes or possibly
      neurogenesis. Clearly, NILT is a treatment that confers neuroprotection or
      neurorestoration using pleiotropic mechanisms. The most advanced application of
      NILT is for acute ischemic stroke based upon extensive preclinical and clinical
      studies. In laboratory settings, NILT is also being developed to treat traumatic
      brain injury, Alzheimer's disease and Parkinson's disease. There is some
      intriguing data in the literature that suggests that NILT may be a method to
      promote clinical improvement in neurodegenerative diseases where there is a
      common mechanistic component, mitochondrial dysfunction and energy impairment.
      This article will analyze and review data supporting the continued development of
      NILT to treat neurodegenerative diseases.

PMID- 22145845
TI  - Hall effect in electrolyte flow measurements: introduction to blood flow
      measurements.
AB  - The Hall effect has been applied to electrolyte flow measurement. It has been
      proven that Hall voltage does not depend on electrolyte concentration; however,
      there is a linear relationship between Hall voltage and flow velocity. Obtained
      results for electrolyte allow us to suppose that Hall effect can be used to
      determine blood flow. Research on blood will be conducted as the next step.

PMID- 22145846
TI  - Ethylene negatively regulates EXPA5 expression in Arabidopsis thaliana.
AB  - We examined the effects of ethylene on the expression of Arabidopsis expansins
      (AtEXPs). Among the AtEXPs tested, transcription of the AtEXPA5 gene was reduced
      most by exogenous ethylene. 2-Aminoethoxyvinylglycine, an ethylene biosynthesis
      inhibitor, increased AtEXPA5 transcription. Ethylene insensitive (ein7) and
      constitutive (ctr1) mutants resulted in increased and decreased transcription,
      respectively, thereby suggesting that ethylene endogenously downregulates AtEXPA5
      expression. Hypocotyl elongation followed the same trend as AtEXPA5 expression,
      implying that changes in hypocotyl elongation reflect changes in AtEXPA5
      expression. A transgenic plant line that overexpresses AtEXPA5, 35S-EXPA5, showed
      a reduced response to exogenous ethylene in terms of hypocotyl lengths when
      compared to wild-type and expA5-1, a knockout mutant. These results and the dose
      dependent effect of aminocyclopropane-1-carboxyl acid on hypocotyl elongation
      implicate AtEXPA5 overexpression in making tissues more sensitive to high doses
      of ethylene. In summary, AtEXPA5 appears to respond to ethylene and play a role
      in ethylene regulating hypocotyl elongation in Arabidopsis thaliana.

PMID- 22145847
TI  - Norovirus outbreak associated with person-to-person transmission, U.S. Air Force
      Academy, July 2011.
AB  - In July 2011, the U.S. Air Force School of Aerospace Medicine (USAFSAM)
      Epidemiology Consult Service investigated an ongoing outbreak of acute
      gastrointestinal (GI) illness--characterized by vomiting, nausea, diarrhea, and
      stomach cramps--that affected cadets and support personnel at a field training
      location at the U.S. Air Force Academy. Six outbreak-related stool specimens were
      confirmed by RT-PCR to be infected with norovirus, genogroup I. Overall, 290
      cases (suspected and confirmed) of norovirus-related GI illness were recorded;
      the estimated attack rate among 1,359 cadets was 18%. The investigation suggested
      that norovirus was introduced into the field dining facility by one or more food
      service workers, possibly transmitted via common use serving utensils, and then
      further spread among cadets by person-to-person contact. Numbers of new cases
      sharply declined after ill cadets were segregated in separate tents for
      convalescence, and after all cadets moved from field billets (i.e., tents) to
      dormitories after completing the field training.

PMID- 22145848
TI  - Historical perspective: norovirus gastroenteritis outbreaks in military forces.

PMID- 22145849
TI  - Poisoning-related hospitalizations and risk factors for self-inflicted poisoning
      in the active component, U.S. Armed Forces, 2001-2010.
AB  - Self-inflicted poisoning is a common method of suicide but results in many more
      injuries than deaths. During 2001-2010 there were 14,979 poisoning-related
      hospitalizations among 13,971 active component military members. Medications for
      pain and psychiatric conditions were the causal agents of two-thirds of all
      poisoning hospitalizations. Rates of hospitalization for poisoning were
      relatively stable during the period; the highest rates were among females,
      teenaged service members, and Army members. Of all poisoning-related
      hospitalizations, approximately two-thirds (67.5%) were estimated as
      intentionally self-inflicted (based on reported "external cause of injury" codes
      and relevant comorbid mental disorder diagnoses).

PMID- 22145850
TI  - Brief report: Morbidity burdens attributable to illnesses and injuries in
      deployed (per Theater Medical Data Store [TMDS]) compared to nondeployed (per
      Defense Medical Surveillance System [DMSS]) settings, active component, U.S.
      Armed Forces, 2010.

PMID- 22145851
TI  - Accuracy of the Enlite 6-day glucose sensor with guardian and Veo calibration
      algorithms.
AB  - OBJECTIVE: This study investigates the accuracy of a newly developed, next
      generation subcutaneous glucose sensor, evaluated for 6-day use. RESEARCH DESIGN
      AND METHODS: Seventy-nine subjects (53 men, 26 women) with type 1 diabetes and 18
      subjects (14 men, four women) with type 2 diabetes completed a three-center,
      prospective, sensor accuracy study. The mean age for the group was 42.2+/-15.0
      years (mean+/-SD), ranging from 18 to 71 years, with a mean glycosylated
      hemoglobin level of 7.6+/-1.5%, ranging from 5.5% to 14%. Subjects wore EnliteTM
      sensors (Medtronic Diabetes, Northridge, CA) in the abdominal and buttocks region
      for two separate 7-day periods and calibrated with a home-use blood glucose
      meter. Subjects participated in an in-clinic testing day where frequent sampled
      plasma glucose samples were acquired every 15 min for 10 h. Sensor data was
      retrospectively processed with Guardian((r)) REAL-Time (Medtronic) and
      Paradigm((r)) VeoTM (Medtronic) calibration routines, and accuracy metrics were
      calculated for each algorithm and sensor location. Physiological time lag for
      each measurement site was calculated. RESULTS: Based on 6,404 plasma-sensor
      glucose paired points, the Enlite sensor with Veo calibration algorithm produced
      a mean absolute relative difference of 13.86% with 97.3% of points within the A+B
      zones of the Clarke error grid. Threshold-only alarms detected 90.1% of
      hypoglycemia and 90% of hyperglycemia. Mean time lag measured at the abdominal
      region was 7.94+/-6.48 min compared with 11.70+/-6.71 min (P<0.0001) at the
      buttocks area. CONCLUSIONS: The Enlite sensor accurately measures glucose when
      compared with gold standard laboratory measurements over its 6-day use. Sensors
      placed in the buttocks region exhibited greater time lags than sensors placed in
      the abdomen.

PMID- 22145852
TI  - Synthesis, structure, chemical bonding, and magnetism of the series RELiGe2 (RE =
      La-Nd, Sm, Eu).
AB  - This article focuses on the synthesis and the crystal chemistry of six members of
      a series of rare-earth metal based germanides with general formula RELiGe(2) (RE
      = La-Nd, Sm, and Eu). The structures of these compounds have been established by
      single-crystal X-ray diffraction (CaLiSi(2) structure type, space group Pnma, Z =
      4, Pearson symbol oP16). The chemical bonding within this atomic arrangement can
      be rationalized in terms of anionic germanium zigzag chains, conjoined via chains
      of edge-shared LiGe(4) tetrahedra and separated by rare-earth metal cations. The
      structure can also be viewed as an intergrowth of AlB(2)-like and TiNiSi-like
      fragments, or as the result of the replacement of 50% of the rare-earth metal
      atoms by lithium in the parent structure of the REGe monogermanides. Except for
      LaLiGe(2) and SmLiGe(2), the remaining four RELiGe(2) phases exhibit Curie-Weiss
      paramagnetism above about 50 K. In the low temperature regime, the localized 4f
      electrons in CeLiGe(2), PrLiGe(2), and SmLiGe(2) order ferromagnetically, while
      antiferromagnetic ordering is observed for NdLiGe(2) and EuLiGe(2). The
      calculated effective magnetic moments confirm RE(3+) ground states in all cases
      excluding EuLiGe(2), in which the magnetic response is consistent with Eu(2+)
      configuration (J = S = 7/2). The experimental results have been complemented by
      tight-binding linear muffin-tin orbital (TB-LMTO) band structure calculations.

PMID- 22145854
TI  - Effects of magnesium-substituted nanohydroxyapatite coating on implant
      osseointegration.
AB  - OBJECTIVE: The objective of this study was to compare magnesium-substituted and
      pure hydroxyapatite coatings on the promotion of osteogenesis in vitro and on the
      osseointegration in vivo. METHODS: Electrochemically deposited pure
      hydroxyapatite (EDHA) or electrochemically deposited magnesium-substituted
      hydroxyapatite (EDMHA) coatings were formed on the surface of pure titanium disks
      or implants. MC3T3-E1 preosteoblasts were cultured in the EDHA and EDMHA coated
      disks, and cell growth, alkaline phosphatase (ALP) activity, and osteocalcin
      secretion were measured at various time points. For studies on osseointegration,
      30 roughened implants coated either with EDHA or EDMHA (n = 15 for each coating)
      were implanted in the femurs of 15 NZW rabbits. After 2, 4, and 8 weeks, femurs
      were retrieved and prepared for histomorphometric evaluation (n = 5 for each
      coating at each time point). RESULTS: MC3T3-E1 cells cultured on EDMHA coated
      disks showed increased cell number, ALP, and osteocalcin secretion compared with
      the EDHA coated disks at all time points (P < 0.05 for all). Histologic
      observation of the coated implants showed woven bone in direct contact with both
      implant surfaces after 2 weeks and mature bone after 8 weeks. While there were no
      differences in the amount of bone between the threads at any time point, the
      percentage of implant in direct contact with bone (bone implant contact) was
      slightly higher along the EDMHA coated implants at 2 weeks (P = 0.086), although
      this difference was no longer seen at 4 and 8 weeks. CONCLUSION: Mg-substituted
      HA coated surfaces promote osteogenic differentiation of preosteoblasts in vitro
      and may improve implant osseointegration during the early stages of bone healing
      compared with pure EDHA coated surfaces.

PMID- 22145853
TI  - Inhibition of HIV-1 endocytosis allows lipid mixing at the plasma membrane, but
      not complete fusion.
AB  - BACKGROUND: We recently provided evidence that HIV-1 enters HeLa-derived TZM-bl
      and lymphoid CEMss cells by fusing with endosomes, whereas its fusion with the
      plasma membrane does not proceed beyond the lipid mixing step. The mechanism of
      restriction of HIV-1 fusion at the cell surface and/or the factors that aid the
      virus entry from endosomes remain unclear. RESULTS: We examined HIV-1 fusion with
      a panel of target cells lines and with primary CD4+ T cells. Kinetic measurements
      of fusion combined with time-resolved imaging of single viruses further
      reinforced the notion that HIV-1 enters the cells via endocytosis and fusion with
      endosomes. Furthermore, we attempted to deliberately redirect virus fusion to the
      plasma membrane, using two experimental strategies. First, the fusion reaction
      was synchronized by pre-incubating the viruses with cells at reduced temperature
      to allow CD4 and coreceptors engagement, but not the virus uptake or fusion.
      Subsequent shift to a physiological temperature triggered accelerated virus
      uptake followed by entry from endosomes, but did not permit fusion at the cell
      surface. Second, blocking HIV-1 endocytosis by a small-molecule dynamin
      inhibitor, dynasore, resulted in transfer of viral lipids to the plasma membrane
      without any detectable release of the viral content into the cytosol. We also
      found that a higher concentration of dynasore is required to block the HIV
      endosome fusion compared to virus internalization. CONCLUSIONS: Our results
      further support the notion that HIV-1 enters disparate cell types through fusion
      with endosomes. The block of HIV-1 fusion with the plasma membrane at a post
      lipid mixing stage shows that this membrane is not conducive to fusion pore
      formation and/or enlargement. The ability of dynasore to interfere with the virus
      endosome fusion suggests that dynamin could be involved in two distinct steps of
      HIV-1 entry - endocytosis and fusion within intracellular compartments.

PMID- 22145855
TI  - Yeast cell based feed additives: studies on aflatoxin B1 and zearalenone.
AB  - Thirty commercially available yeast cell wall products and two reference
      bentonites were tested for their ability to bind aflatoxin B(1) (AFB1) and
      zearalenone (ZON) in buffer solutions at pH 3 and pH 6.5 as well as in real
      gastric juice. For most products, the binding efficacy of AFB1 correlated with
      the ash content, which was between 2.6 and 89%, and constituted the inorganic non
      volatile components, such as mineral clays, of the samples. Samples with smectite
      as the main ash component showed the highest binding efficacy; yet, a correlation
      with the content of mannanooligosaccharides (MOS) and beta-glucans from yeast
      cell walls was not observed. Products containing >30% ash showed AFB1 adsorption
      values >90% at least in one of the investigated media whereas most products with
      <10% ash did not exceed adsorption rates of 20%. In the case of ZON, adsorption
      efficiency ranged between 10 and 60%. It tended to be lowest for products with
      MOS and beta-glucan contents <10% and greatest for products with MOS and beta
      glucan contents >50%. However, there was no general correlation between the
      adsorption of ZON and the concentration of MOS and beta-glucans. Different
      products of one brand sold in different countries were observed to bind AFB1 to
      different degrees, which was explained by the difference in ash contents and
      mineral composition. In the case of ZON, differences in adsorption between
      products of the same brand were less pronounced.

PMID- 22145856
TI  - Targeting of pro-apoptotic TLR adaptor SARM to mitochondria: definition of the
      critical region and residues in the signal sequence.
AB  - The fifth and the most well-conserved member of the TLR (Toll-like receptor)
      adaptor, SARM (sterile alpha- and HEAT/armadillo-motif-containing protein), has
      been reported to be an important mediator of apoptosis. However, the exact
      cellular localization of SARM with respect to its role is unclear. In the present
      study we show that SARM specifically co-localizes with mitochondria. Endogenous
      SARM is mainly found in the mitochondria. We demonstrate that the N-terminal 27
      amino acids (S27) of SARM, which is hydrophobic and polybasic, acts as a
      mitochondria-targeting signal sequence, associating SARM to the mitochondria. The
      S27 peptide has an inherent ability to bind to lipids and mitochondria. This
      sequence effectively translocates the soluble EGFP (enhanced green fluorescence
      protein) reporter into the mitochondria. Positioning S27 downstream of the EGFP
      abrogates its mitochondria-targeting ability. Transmission electron microscopy
      confirms the ability of S27 to import EGFP into the mitochondria. Importantly, by
      mutagenesis study, we delineated the specificity of the mitochondria-targeting
      ability to the arginine residue at the 14th position. The R14A SARM mutant also
      showed reduced apoptotic potential when compared with the wild-type. Taken
      together, S27, which is a bona fide signal sequence that targets SARM to the
      mitochondria, explains the pro-apoptotic activity of SARM.

PMID- 22145858
TI  - T-cell acute lymphoblastic leukaemia: recent molecular biology findings.
AB  - For many years, T-cell acute lymphoblastic leukaemia (T-ALL) has been considered
      and treated as a single malignancy, but divergent outcomes in T-ALL patients
      receiving uniform treatment protocols encouraged intensive research on the
      molecular biology of this disease. Recent findings in the field demonstrate that
      T-ALL is much more heterogeneous than originally believed and extremely diverse
      outcomes of patients require refinement of T-ALL classification, leading to
      subtype-specific adjustment of treatment. Many different biological features of T
      ALL blast cells have recently been found to contribute to disease development and
      patient outcome and their analysis could potentially be introduced into improved
      diagnostics and classification of the disease. This review focuses on five key
      issues of T-ALL biology: chromosome aberrations, gene expression profiles, gene
      mutations, DNA methylation patterns, and immunoglobulin/T cell receptor (Ig/TCR)
      gene rearrangements. Additionally, molecular monitoring of minimal residual
      disease, by far the most reliable independent prognostic factor in T-ALL, has
      been highlighted in the context of Ig/TCR gene rearrangements. Translation of
      this biological information into better prognostic classification and more
      effective treatment should lead to improvement of outcome in T-ALL patients.

PMID- 22145857
TI  - Amaranthus spinosus Linn. inhibits mast cell-mediated anaphylactic reactions.
AB  - The current study characterizes the mechanism by which the Amaranthus spinosus
      (Amaranthaceae) decreases mast cell-mediated anaphylactic reactions. Anaphylaxis
      is a typical hypersensitivity Type I reaction, sharing common mechanisms with
      asthma in its early and late phases. Mast cells are key as effector cells in
      hypersensitivity Type I reactions. A. spinosus has been traditionally used in the
      treatment of allergic bronchitis and asthma, but its role in mast cell-mediated
      anaphylactic reactions has not fully been investigated. This report investigated
      the potential effects of the ethyl acetate fraction of A. spinosus leaves (EAFAS)
      against a compound 48/80 (potent secretagogue)-induced systemic anaphylactic
      shock paradigm in a mouse model. In addition, rat peritoneal mast cells (RPMC)
      were used in in vitro studies to investigate the effect of EAFAS on compound
      48/80-induced peritoneal mast cell degranulation and histamine release. When
      administration by the oral route-1 h before compound 48/80 injection-EAFAS (at
      dose from 0.001-1 g/kg) completely inhibited the induced anaphylactic shock.
      EAFAS at concentrations ranging 0.25-1 mg/ml dose-dependently attenuated rates of
      mast cell degranulation and histamine release from RPMC that were evoked by
      compound 48/80. The results of the present investigation indicated that EAFAS
      stabilizes the mast cell lipid bilayer membrane, thereby preventing the
      perturbation of membrane and the release of histamine. As a result of these anti
      degranulating and anti-histaminic effects, it can be suggested that EAFAS may
      have a potential use in the prophylaxis and management of anaphylactic reactions.

PMID- 22145859
TI  - Estimating the costs of induced abortion in Uganda: a model-based analysis.
AB  - BACKGROUND: The demand for induced abortions in Uganda is high despite legal and
      moral proscriptions. Abortion seekers usually go to illegal, hidden clinics where
      procedures are performed in unhygienic environments by under-trained
      practitioners. These abortions, which are usually unsafe, lead to a high rate of
      severe complications and use of substantial, scarce healthcare resources. This
      study was performed to estimate the costs associated with induced abortions in
      Uganda. METHODS: A decision tree was developed to represent the consequences of
      induced abortion and estimate the costs of an average case. Data were obtained
      from a primary chart abstraction study, an on-going prospective study, and the
      published literature. Societal costs, direct medical costs, direct non-medical
      costs, indirect (productivity) costs, costs to patients, and costs to the
      government were estimated. Monte Carlo simulation was used to account for
      uncertainty. RESULTS: The average societal cost per induced abortion (95%
      credibility range) was $177 ($140-$223). This is equivalent to $64 million in
      annual national costs. Of this, the average direct medical cost was $65 ($49-86)
      and the average direct non-medical cost was $19 ($16-$23). The average indirect
      cost was $92 ($57-$139). Patients incurred $62 ($46-$83) on average while
      government incurred $14 ($10-$20) on average. CONCLUSION: Induced abortions are
      associated with substantial costs in Uganda and patients incur the bulk of the
      healthcare costs. This reinforces the case made by other researchers--that
      efforts by the government to reduce unsafe abortions by increasing contraceptive
      coverage or providing safe, legal abortions are critical.

PMID- 22145860
TI  - Genus Enhydrobacter Staley et al. 1987 should be recognized as a member of the
      family Rhodospirillaceae within the class Alphaproteobacteria.
AB  - The genus Enhydrobacter, first reported as a member of the family Vibrionaceae,
      has been placed in the family Moraxellaceae, but as a genus incertae sedis in
      Bergey's Manual of Systematic Bacteriology 2nd edition. During our taxonomic
      investigation of Enhydrobacter-like organisms, we observed that the 16S rRNA
      sequences of E. aerosaccus-type strain versions NCIMB 12535(T) , ATCC 27094( T)
      and CCUG 58314(T) were very different from the accessible data (accession no.
      AJ550856). Phylogenetic analysis of our 16S rRNA sequence data revealed that
      these organisms were located within the family Rhodospirillaceae. The genera
      Inquilinus, Oceanibaculum, Skermanella and Nisaea were closely related (sequence
      similarities were 88.3~87.0%), but Enhydrobacter could be distinguished from
      these genera by growth characteristics, fatty acid profiles (C(19:0) cyclo
      omega8c; 38.4% C(18:1) omega7c; 32.2%, and C(16:0) ; 8.9% were major components),
      in being non-flagellated, and differing in enzymatic activities, including
      trypsin and beta-glucosidase. From these data, we conclude that the genus
      Enhydrobacter should be recognized as an independent genus of the family
      Rhodospirillaceae within the class Alphaproteobacteria.

PMID- 22145861
TI  - Evaluation of maximum voided volume in Korean children by use of a 48-h frequency
      volume chart.
AB  - Study Type - Diagnostic (validating cohort). Level of Evidence 2a. What's known
      on the subject? and What does the study add? The relationship between the maximum
      voided volume followed a linear curve. The formula presented, bladder capacity
      (mL) = 12 *[age (years) + 11], is thought to be a reasonable one for Korean
      children. Korean children have a smaller bladder capacity than that reported in
      previous Western studies. OBJECTIVE: * To develop practical guidelines for the
      prediction of normal bladder capacity in Korean children measured by a frequency
      volume chart (FVC), maximum voided volume (MVV) is an important factor in the
      diagnosis of children with abnormal voiding function. SUBJECTS AND METHODS: * In
      all, 298 children, aged 3-13 years, with no history of voiding disorders
      volunteered for the study. The MVV was determined in 219 subjects by use of a
      completely recorded FVC. RESULTS: * Linear regression analysis was used to define
      the exact relationship between age and bladder capacity. An approximate formula
      related age to bladder capacity as follows: bladder capacity (mL) = 12 *[age
      (years) + 11]. CONCLUSIONS: * The relationship between the MVV measured by a FVC
      by age (3-13 years) of Korean children followed a linear curve. * When applied to
      normal voiding patterns, the formula presented appears to be a reasonable one for
      Korean children.

PMID- 22145862
TI  - Novel analysis of clinically relevant diagnostic errors in point-of-care devices:
      a rebuttal.

PMID- 22145863
TI  - Strange bedfellows: meta-narrative traditions in the alcohol and other drug
      field.

PMID- 22145864
TI  - Modulation of glutamate release from parallel fibers by mGlu4 and pre-synaptic
      GABA(A)  receptors.
AB  - The regulation of pre-synaptic glutamate release is important in the maintenance
      and fidelity of excitatory transmission in the nervous system. In this study, we
      report a novel interaction between a ligand-gated ion channel and a G-protein
      coupled receptor which regulates glutamate release from parallel fiber axon
      terminals. Immunocytochemical analysis revealed that GABA(A) receptors and the
      high affinity group III metabotropic glutamate receptor subtype 4 (mGlu4) are co
      localized on glutamatergic parallel fiber axon terminals in the cerebellum.
      GABA(A) and mGlu4 receptors were also found to co-immunoprecipitate from
      cerebellar membranes. Independently, these two receptors have opposing roles on
      glutamate release: pre-synaptic GABA(A) receptors promote, while mGlu4 receptors
      inhibit, glutamate release. However, coincident activation of GABA(A) receptors
      with muscimol and mGlu4 with the agonist (2S)-S-2-amino-4-phosphonobutanoic acid
      , increased glutamate release from [(3) H]glutamate-loaded cerebellar
      synaptosomes above that observed with muscimol alone. Further support for an
      interaction between GABA(A) and mGlu4 receptors was obtained in the mGlu4
      knockout mouse which displayed reduced binding of the GABA(A) ligand [(35) S]tert
      butylbicyclophosphorothionate, and decreased expression of the alpha1, alpha6,
      beta2 GABA(A) receptor subunits in the cerebellum. Taken together, our data
      suggest a new role for mGlu4 whereby simultaneous activation with GABA(A)
      receptors acts to amplify glutamate release at parallel fiber-Purkinje cell
      synapses.

PMID- 22145865
TI  - Genomic profiling of renal cell carcinoma in patients with end-stage renal
      disease.
AB  - The purpose of the present study was to determine the genomic profile of renal
      cell carcinoma (RCC) in end-stage renal disease (ESRD) by analyzing genomic copy
      number aberrations. Seventy-nine tumor samples from 63 patients with RCC-ESRD
      were analyzed by array comparative genomic hybridization using the Agilent Whole
      Human Genome 4 * 44K Oligo Micro Array (Agilent Technologies Inc., Palo Alto, CA,
      USA). Unsupervised hierarchical clustering analysis revealed that the 63 cases
      could be divided into two groups, Clusters A and B. Cluster A was comprised
      mainly of clear cell RCC (CCRCC), whereas Cluster B was comprised mainly of
      papillary RCC (PRCC), acquired cystic disease (ACD)-associated RCC, and clear
      cell papillary RCC. Analysis of the averaged frequencies revealed that the
      genomic profiles of Clusters A and B resembled those of sporadic CCRCC and
      sporadic PRCC, respectively. Although it has been proposed on the basis of
      histopathology that ACD-associated RCC, clear cell papillary RCC and PRCC-ESRD
      are distinct subtypes, the present data reveal that the genomic profiles of these
      types, categorized as Cluster B, resemble one another. Furthermore, the genomic
      profiles of PRCC, ACD-associated RCC and clear cell papillary RCC admixed in one
      tissue tended to resemble one another. On the basis of genomic profiling of RCC
      ESRD, we conclude that the molecular pathogenesis of CCRCC-ESRD resembles that of
      sporadic CCRCC. Although various histologic subtypes of non-clear cell RCC-ESRD
      have been proposed, their genomic profiles resemble those of sporadic PRCC,
      suggesting that the molecular pathogenesis of non-CCRCC-ESRD may be related to
      that of sporadic PRCC.

PMID- 22145866
TI  - Universal COI primers for DNA barcoding amphibians.
AB  - DNA barcoding is a proven tool for the rapid and unambiguous identification of
      species, which is essential for many activities including the vouchering tissue
      samples in the genome 10K initiative, genealogical reconstructions, forensics and
      biodiversity surveys, among many other applications. A large-scale effort is
      underway to barcode all amphibian species using the universally sequenced DNA
      region, a partial fragment of mitochondrial cytochrome oxidase subunit I COI.
      This fragment is desirable because it appears to be superior to 16S for
      barcoding, at least for some groups of salamanders. The barcoding of amphibians
      is essential in part because many species are now endangered. Unfortunately,
      existing primers for COI often fail to achieve this goal. Herein, we report two
      new pairs of primers (?, ?) that in combination serve to universally amplify and
      sequence all three orders of Chinese amphibians as represented by 36 genera. This
      taxonomic diversity, which includes caecilians, salamanders and frogs, suggests
      that the new primer pairs will universally amplify COI for the vast majority
      species of amphibians.

PMID- 22145867
TI  - Direct production of biodiesel from high-acid value Jatropha oil with solid acid
      catalyst derived from lignin.
AB  - BACKGROUND: Solid acid catalyst was prepared from Kraft lignin by chemical
      activation with phosphoric acid, pyrolysis and sulfuric acid. This catalyst had
      high acid density as characterized by scanning electron microscope (SEM), energy
      dispersive x-ray spectrometry (EDX) and Brunauer, Emmett, and Teller (BET) method
      analyses. It was further used to catalyze the esterification of oleic acid and
      one-step conversion of non-pretreated Jatropha oil to biodiesel. The effects of
      catalyst loading, reaction temperature and oil-to-methanol molar ratio, on the
      catalytic activity of the esterification were investigated. RESULTS: The highest
      catalytic activity was achieved with a 96.1% esterification rate, and the
      catalyst can be reused three times with little deactivation under optimized
      conditions. Biodiesel production from Jatropha oil was studied under such
      conditions. It was found that 96.3% biodiesel yield from non-pretreated Jatropha
      oil with high-acid value (12.7 mg KOH/g) could be achieved. CONCLUSIONS: The
      catalyst can be easily separated for reuse. This single-step process could be a
      potential route for biodiesel production from high-acid value oil by simplifying
      the procedure and reducing costs.

PMID- 22145868
TI  - Scent recognition of infected status in humans.
AB  - INTRODUCTION: There is a body of experimental evidence that mice and rats use
      chemical signals to avoid sexual contact with infected conspecifics. In contrast
      to animals, body scent of sick humans is employed only in medical diagnostics. A
      modification of human body odor, due to an infection, has not been studied as a
      potential signal for choice of a sexual partner. It might, however, be especially
      important for sexually transmitted infections (STI) because many such infections
      have no obvious external manifestations. AIM: In this study, we have investigated
      odor pleasantness of young men infected with gonorrhea, Neisseria gonorrhoeae.
      METHODS: We collected armpit sweat and saliva from young men (17-25 years old)
      belonging to three groups: healthy persons (N = 16), young men infected with
      gonorrhea, Neisseria gonorrhoeae (N = 13), and persons recovered due to specific
      therapy (N = 5). The sweat samples odor was then assessed by healthy young women
      (17-20 years old). Concentrations of cortisol, testosterone, immunoglobulin A
      (IgA), and immunoglobulin G (IgG) were measured in saliva by means of enzyme
      linked immunosorbent assay. MAIN OUTCOME MEASURES: Subjective rates of odor
      pleasantness, association of scent of armpit sweat with odor descriptors,
      stepwise regression of odor pleasantness and salivary cortisol, testosterone,
      IgA, and IgG. RESULTS: The odor from infected individuals was reported as less
      pleasant in comparison with the odor of healthy and recovered young men. The
      scent of infected men was more frequently associated by raters with the
      descriptor "putrid." Odor pleasantness of the male sweat correlated negatively
      with concentration of the nonspecific salivary IgA and IgG, which was measured as
      an indicator of current immunoenhancement. CONCLUSION: Perhaps, the immune
      dependent reduction of the scent pleasantness in the acute phase of STI is part
      of an evolutionary mechanism ensuring, unconsciously, avoidance of a risky
      romantic partner.

PMID- 22145869
TI  - Population branching in the conical intersection of the retinal chromophore
      revealed by multipulse ultrafast optical spectroscopy.
AB  - The branching ratio of the excited-state population at the conical intersection
      between the S(1) and S(0) energy surfaces (Phi(CI)) of a protonated Schiff base
      of all-trans retinal in protic and aprotic solvents was studied by multipulse
      ultrafast transient absorption spectroscopy. In particular, pump-dump-probe
      experiments allowed to isolate the S(1) reactive state and to measure the
      photoisomerization time constant with unprecedented precision. Starting from
      these results, we demonstrate that the polarity of the solvent is the key factor
      influencing the Phi(CI) and the photoisomerization yield.

PMID- 22145870
TI  - Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing
      and contrasting values.
AB  - The primate orbitofrontal cortex (OFC) is often treated as a single entity, but
      architectonic and connectional neuroanatomy indicate that it has distinguishable
      parts. Nevertheless, few studies have attempted to dissociate the functions of
      its subregions. Here we review findings from recent neuropsychological and
      neurophysiological studies that do so. The lateral OFC seems to be important for
      learning, representing, and updating specific object-reward associations. The
      medial OFC seems to be important for value comparisons and choosing among objects
      on that basis. Rather than viewing this dissociation of function in terms of
      learning versus choosing, however, we suggest that it reflects the distinction
      between contrasts and comparisons: differences versus similarities. Making use of
      high-dimensional representations that arise from the convergence of several
      sensory modalities, the lateral OFC encodes contrasts among outcomes. The medial
      OFC reduces these contrasting representations of value to a single dimension, a
      common currency, in order to compare alternative choices.

PMID- 22145871
TI  - Giving credit where credit is due: orbitofrontal cortex and valuation in an
      uncertain world.
AB  - The orbitofrontal cortex (OFC) has long been implicated in aspects of learning
      and adaptive decision making in changeable environments, but its precise role has
      remained elusive. One potential reason is that anatomical and functional
      distinctions within the OFC have often been overlooked. Here, we review findings
      centered largely on recent lesion studies in macaque monkeys from our
      laboratories that have investigated the causal role of the lateral and medial
      parts of the OFC (LOFC and MOFC) in choice behavior in uncertain, multioption
      environments. MOFC appears necessary for focusing attention on only the relevant
      decision variables to achieve a goal. By contrast, LOFC is required to allow
      rapid learning in changeable environments by enabling the credit for a particular
      outcome to be assigned to a specific choice.

PMID- 22145872
TI  - The orbitofrontal cortex and response selection.
AB  - Orbitofrontal cortex (OFC) function is often characterized in terms of stimulus
      reward mapping; however, more recent evidence suggests that the OFC may play a
      role in selecting and representing extended actions. First, previously encoded
      reward associations in the OFC could be used to inform responding in novel but
      similar situations. Second, when evaluated in tasks requiring the animal to
      perform extended actions, response selective activity can be recorded in the OFC.
      Finally, the interaction between the OFC and hippocampus illustrates OFC's role
      in response selection. The OFC may facilitate reward-guided memory retrieval by
      selecting the memories most relevant to achieve a goal. This model for OFC
      function places it within the hierarchy of increasingly complex action
      representations that support decision making.

PMID- 22145873
TI  - Contrasting reward signals in the orbitofrontal cortex and anterior cingulate
      cortex.
AB  - Damage to the orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC)
      impairs decision making, but the underlying value computations that cause such
      impairments remain unclear. Both the OFC and ACC encode a wide variety of signals
      correlated with decision making. The current challenge is to determine how these
      two different areas support decision-making processes. Here, we review a series
      of experiments that have helped define these roles. A special population of
      neurons in the ACC, but not the OFC, multiplex value information across decision
      parameters using a unified encoding scheme, and encode reward prediction errors.
      In contrast, neurons in the OFC, but not the ACC, encode the value of a choice
      relative to the recent history of choice values. Together, these results suggest
      complementary valuation processes: OFC neurons dynamically evaluate current
      choices relative to the value contexts recently experienced, while ACC neurons
      encode choice predictions and prediction errors using a common valuation currency
      reflecting the integration of multiple decision parameters.

PMID- 22145874
TI  - The orbitofrontal cortex, predicted value, and choice.
AB  - Considerable evidence suggests that choice between goal-directed actions depends
      on two incentive processes encoding the reward value of the goal or outcome and
      the predicted value of an action based on outcome-related stimuli. Although
      incentive theories generally assume that these processes are mediated by a common
      associative mechanism, a number of recent findings suggest that they are
      dissociable; the reward value of an action is derived from consummatory
      experience with the outcome itself, whereas the predicted value of an action is
      based on the presence of outcome-associated stimuli from which estimates of the
      likelihood of an outcome are derived. Importantly, the orbitofrontal cortex (OFC)
      in rodents appears to mediate the effect of outcome-related stimuli on choice;
      OFC lesions disrupt the influence of Pavlovian stimuli on choice in tests of
      outcome-specific Pavlovian-instrumental transfer. However, the influence of
      outcome-related stimuli on choice involves a larger circuit including the OFC,
      the ventral striatum, and the amygdala. How these structures interact, however,
      is not yet fully understood and is an important question for future research.

PMID- 22145875
TI  - Orbitofrontal contributions to value-based decision making: evidence from humans
      with frontal lobe damage.
AB  - The work described here aims to isolate the component processes of decision
      making that rely critically on particular subregions of the human prefrontal
      cortex, with a particular focus on the orbitofrontal cortex. Here, experiments
      isolating specific aspects of decision making, using very simple preference
      judgment and reinforcement learning paradigms, were carried out in patients with
      focal frontal damage. The orbitofrontal cortex and the adjacent ventromedial
      prefrontal cortex play a critical role in decisions based on subjective value,
      across many categories of stimuli, and in learning to choose between stimuli
      based on value feedback. However, these regions are not required for learning to
      choose between actions based on feedback, which instead seems to rely critically
      on the dorsomedial prefrontal cortex. These results point to a potentially common
      role for the orbitofrontal cortex in representing the context-sensitive,
      subjective value of stimuli to allow consistent choices between them. They also
      argue for multiple, parallel, value-based processes that influence behavior
      through dissociable mechanisms.

PMID- 22145876
TI  - Representations of appetitive and aversive information in the primate
      orbitofrontal cortex.
AB  - Individuals weigh information about both rewarding and aversive stimuli to make
      adaptive decisions. Most studies of the orbitofrontal cortex (OFC), an area where
      appetitive and aversive neural subsystems might interact, have focused only on
      reward. Using a classical conditioning task where novel stimuli are paired with a
      reward or an aversive air puff, we discovered that two groups of orbitofrontal
      neurons respond preferentially to conditioned stimuli associated with rewarding
      and aversive outcomes; however, information about appetitive and aversive stimuli
      converges on individual neurons from both populations. Therefore, neurons in the
      OFC might participate in appetitive and aversive networks that track the
      motivational significance of stimuli even when they vary in valence and sensory
      modality. Further, we show that these networks, which also extend to the
      amygdala, exhibit different rates of change during reversal learning. Thus,
      although both networks represent appetitive and aversive associations, their
      distinct temporal dynamics might indicate different roles in learning processes.

PMID- 22145877
TI  - Behavioral outcomes of late-onset or early-onset orbital frontal cortex (areas
      11/13) lesions in rhesus monkeys.
AB  - The orbital frontal cortex (OFC) has been implicated in a number of psychiatric
      disorders, including depression, anxiety, phobia, and obsessive-compulsive
      disorder. Thus, a better understanding of its functions will likely provide
      critical information to understand the specific behavioral and cognitive
      processes affected in these human disorders. In recent years, a growing number of
      studies have provided evidence for anatomical and functional differentiation
      within the OFC. Here we discuss the effects of selective OFC (areas 11/13)
      lesions on social behavior, emotional regulation, and behavioral adaptation.
      Damage to these specific OFC subfields in adult monkeys resulted in profound
      changes in the flexible modulation of responses guided by reward value that could
      explain the poor fear regulation and disturbed social interactions observed in
      the same animals. A similar pattern of results was found when the OFC lesions
      were done in infancy. Thus, in monkeys, self-regulation abilities mediated by OFC
      areas 11/13 emerge from midinfancy through adolescence.

PMID- 22145878
TI  - Does the orbitofrontal cortex signal value?
AB  - The orbitofrontal cortex (OFC) has long been implicated in associative learning.
      Early work by Mishkin and Rolls showed that the OFC was critical for rapid
      changes in learned behavior, a role that was reflected in the encoding of
      associative information by orbitofrontal neurons. Over the years, new data
      particularly neurophysiological data-have increasingly emphasized the OFC in
      signaling actual value. These signals have been reported to vary according to
      internal preferences and judgments and to even be completely independent of the
      sensory qualities of predictive cues, the actual rewards, and the responses
      required to obtain them. At the same time, increasingly sophisticated behavioral
      studies have shown that the OFC is often unnecessary for simple value-based
      behavior and instead seems critical when information about specific outcomes must
      be used to guide behavior and learning. Here, we review these data and suggest a
      theory that potentially reconciles these two ideas, value versus specific
      outcomes, and bodies of work on the OFC.

PMID- 22145880
TI  - Neuronal signals for reward risk in frontal cortex.
AB  - Rewards can be viewed as probability distributions of reward values. Besides
      expected (mean) value, a key parameter of such distributions is variance (or
      standard deviation), which constitutes a measure of risk. Single neurons in
      orbitofrontal cortex signal risk mostly separately from value. Comparable risk
      signals in human frontal cortex reflect risk attitudes of individual
      participants. Subjective outcome value constitutes the primary economic decision
      variable. The terms risk avoidance and risk taking suggest that risk affects
      subjective outcome value, a basic tenet of economic decision theories.
      Correspondingly, risk reduces neuronal value signals in frontal cortex of human
      risk avoiders and enhances value signals in risk takers. Behavioral contrast
      effects and reference-dependent valuation demonstrate flexible reward valuation.
      As a potential correlate, value signals in orbitofrontal neurons adjust reward
      discrimination to variance (risk). These neurophysiological mechanisms of reward
      risk on economic decisions inform and validate theories of economic decision
      making under uncertainty.

PMID- 22145879
TI  - The prefrontal cortex and hybrid learning during iterative competitive games.
AB  - Behavioral changes driven by reinforcement and punishment are referred to as
      simple or model-free reinforcement learning. Animals can also change their
      behaviors by observing events that are neither appetitive nor aversive when these
      events provide new information about payoffs available from alternative actions.
      This is an example of model-based reinforcement learning and can be accomplished
      by incorporating hypothetical reward signals into the value functions for
      specific actions. Recent neuroimaging and single-neuron recording studies showed
      that the prefrontal cortex and the striatum are involved not only in
      reinforcement and punishment, but also in model-based reinforcement learning. We
      found evidence for both types of learning, and hence hybrid learning, in monkeys
      during simulated competitive games. In addition, in both the dorsolateral
      prefrontal cortex and orbitofrontal cortex, individual neurons heterogeneously
      encoded signals related to actual and hypothetical outcomes from specific
      actions, suggesting that both areas might contribute to hybrid learning.

PMID- 22145881
TI  - Contributions of the ventromedial prefrontal cortex to goal-directed action
      selection.
AB  - In this article, it will be argued that one of the key contributions of the
      ventromedial prefrontal cortex (vmPFC) to goal-directed action selection lies
      both in retrieving the value of goals that are the putative outcomes of the
      decision process and in establishing a relative preference ranking for these
      goals by taking into account the value of each of the different goals under
      consideration in a given decision-making scenario. These goal-value signals are
      then suggested to be used as an input into the on-line computation of action
      values mediated by brain regions outside of the vmPFC, such as parts of the
      parietal cortex, supplementary motor cortex, and dorsal striatum. Collectively,
      these areas can be considered to be constituent elements of a multistage decision
      process whereby the values of different goals must first be represented and
      ranked before the value of different courses of action available for the pursuit
      of those goals can be computed.

PMID- 22145883
TI  - The value of identity: olfactory notes on orbitofrontal cortex function.
AB  - Neuroscientific research has emphatically promoted the idea that the key function
      of the orbitofrontal cortex (OFC) is to encode value. Associative learning
      studies indicate that OFC representations of stimulus cues reflect the predictive
      value of expected outcomes. Neuroeconomic studies suggest that the OFC distills
      abstract representations of value from discrete commodities to optimize choice.
      Although value-based models provide good explanatory power for many different
      findings, these models are typically disconnected from the very stimuli and
      commodities giving rise to those value representations. Little provision is made,
      either theoretically or empirically, for the necessary cooperative role of object
      identity, without which value becomes orphaned from its source. As a step toward
      remediating the value of identity, this review provides a focused olfactory
      survey of OFC research, including new work from our lab, to highlight the
      elemental involvement of this region in stimulus-specific predictive coding of
      both perceptual outcomes and expected values.

PMID- 22145884
TI  - Population coding and neural rhythmicity in the orbitofrontal cortex.
AB  - The orbitofrontal cortex has been implicated in the prediction of valuable
      outcomes based on environmental stimuli. However, it remains unknown how it
      represents outcome-predictive information at the population level, and how it
      provides temporal structure to such representations. Here, we pay attention
      especially to the population coding of probabilistic reward, and to the
      importance of orbitofrontal theta- and gamma-band rhythmicity in relation to
      target areas. When rats learned to associate odors to food outcome with variable
      likelihood, we found single-cell and population coding of reward probability, but
      not uncertainty. In related experiments, reward anticipation correlated to firing
      activity locking to theta-band oscillations. In contrast, gamma-band activity was
      associated with a firing-rate suppression of neurons that was most active during
      goal-directed movement. Orbitofrontal coding of outcome-relevant parameters
      appears bound to all relevant temporal phases of behavioral tasks, has a
      distributed nature, and is temporally structured according to multiple modes of
      rhythmicity.

PMID- 22145882
TI  - The orbitofrontal cortex and the computation of subjective value: consolidated
      concepts and new perspectives.
AB  - Remarkable progress has been made in recent years toward understanding the
      functions of the orbitofrontal cortex (OFC). The finding that neurons in this
      area encode the subjective value monkeys assign to different goods while making
      choices has been confirmed and extended by numerous studies using both primate
      neurophysiology and human imaging. Moreover, new lesion studies demonstrated that
      subjective values computed in the OFC are causally and specifically related to
      choice behavior. Importantly, values in the OFC are attached to goods, not to
      actions or to spatial locations. Furthermore, subjective values appear to be
      computed in this area even if the situation does not require a choice. In the
      light of this growing body of work, we propose that the primary function of the
      OFC is the computation of good identities and subjective values in an abstract
      representation. In this view, OFC neurons compute the subjective value of a good
      whenever that good is behaviorally relevant.

PMID- 22145885
TI  - A coordination complex system for generic, ultrafast, and sensitive multimode
      fluorescent staining of biomolecules.
AB  - Gel electrophoresis staining methodologies documented thus far are largely
      utilized in a biomolecule context-dependent manner. We report herein the
      development of a generic, ultrafast, and sensitive multimode fluorescent system
      for the efficient identification of DNA, RNA, and proteins. Interaction between a
      positively charged, planar ligand-based coordination complex with partner
      biomolecule leads to aggregation-induced fluorescence quenching and allows for
      the image contrast generation within one minute. Alternatively, successive
      reactions of the biomolecule-loaded gel with cation and ligand, in either order
      of sequence, provide an equally effective staining efficacy. Image contrast
      reversal is accomplished through a facile washing or photobleaching procedure.
      The versatility in the applicable target species and signal generation modes
      provides a hint at the design of novel staining structures and potentially
      enables the high-throughput readout of biomolecules.

PMID- 22145886
TI  - Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons
      and glia implicated in peripheral and central sensitization.
AB  - BACKGROUND: Calcitonin gene-related peptide (CGRP), a neuropeptide released from
      trigeminal nerves, is implicated in the underlying pathology of temporomandibular
      joint disorder (TMD). Elevated levels of CGRP in the joint capsule correlate with
      inflammation and pain. CGRP mediates neurogenic inflammation in peripheral
      tissues by increasing blood flow, recruiting immune cells, and activating sensory
      neurons. The goal of this study was to investigate the capability of CGRP to
      promote peripheral and central sensitization in a model of TMD. RESULTS: Temporal
      changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus
      were determined by immunohistochemistry following injection of CGRP in the
      temporomandibular joint (TMJ) capsule of male Sprague-Dawley rats. CGRP
      stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA
      in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in
      the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast,
      levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in
      response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes
      and OX-42 in microglia at 2 and 24 hours post injection. CONCLUSIONS: Our results
      demonstrate that an elevated level of CGRP in the joint, which is associated with
      TMD, stimulate neuronal and glial expression of proteins implicated in the
      development of peripheral and central sensitization. Based on our findings, we
      propose that inhibition of CGRP-mediated activation of trigeminal neurons and
      glial cells with selective non-peptide CGRP receptor antagonists would be
      beneficial in the treatment of TMD.

PMID- 22145887
TI  - In vivo and ex vivo phagocytic potential of macrophages from progeny of breeder
      hens kept on ochratoxin A (OTA)-contaminated diet.
AB  - This study aimed to investigate the phagocytic potential of macrophages in
      progeny of breeder hens kept on an OTA-contaminated diet. For this purpose, 84
      White Leghorn (WL) layer breeder hens (40-weeks-of-age) were divided into seven
      groups (A-G). Hens in Group A were fed a commercial layer ration while those in
      Groups B-G were kept on a diet amended with 0.1, 0.5, 1.0, 3.0, 5.0, or 10.0 mg
      OTA/kg, respectively, for up to 3 weeks (n = 12/treatment group; n = 4/time sub
      group/treatment group). Fertile eggs were set for hatching on a weekly basis to
      get the progeny of each week separately. Hatched chicks (n = 10 from each group)
      were injected with India ink at day 14-of-age to study the in vivo phagocytosis
      of carbon particles. At day 30, abdominal macrophages were collected from 15
      chicks/group and were used to assess their ex vivo/in vitro phagocytic potential
      against sheep red blood cells (SRBC) as well as for nitrite production upon
      challenge with lipopolysaccharide (LPS). The phagocytic indices of the
      reticuloendothelial system of all three sets of progeny (chicks obtained from
      hens fed OTA for 7, 14, and 21 days) were significantly lower than values seen
      with Group A chicks. The number of macrophages that were actively phagocytic, the
      number of SRBC internalized per macrophage, and the extent of nitrite production
      after stimulation with LPS were each significantly lower in the cells obtained
      from chicks of breeder hens that had been maintained on the OTA-contaminated
      diets. The findings of this study clearly showed that there are immunosuppressive
      effects-in terms of depressed in vivo and in vitro macrophage functionality-in
      progeny of OTA-fed breeder hens.

PMID- 22145889
TI  - Martyrs in palliative care.

PMID- 22145890
TI  - The value of expert opinion in guiding policy development to support better care
      of the dying in Australasia: a response to the letter by Chan and Webster.

PMID- 22145891
TI  - Searching for a simple assessment tool capable of estimating quality of life in
      palliative care clinical practice: is a feeling of well-being a good candidate
      tool as a single item?

PMID- 22145892
TI  - Progressing an evidence-base beyond case series.

PMID- 22145893
TI  - High scores on the Edmonton Symptom Assessment Scale identify patients with self
      defined high symptom burden.
AB  - The terms symptom burden and symptom distress are frequently seen in palliative
      care literature yet are used in multiple ways ranging from addition of symptom
      scores to more in-depth assessments of interference in function. Patient input to
      date has had little role in these varied definitions yet previous reviews have
      suggested the importance of such input. This mixed qualitative and quantitative
      prospective study was conducted to seek patient input into the definition of
      'symptom burden' and to correlate burden self-ranked scores with symptom scores
      on the Edmonton Symptom Assessment Scale (ESAS). Results suggest that patients
      with advanced disease followed by palliative care providers are a group with a
      high level of self-defined burden. Further, any patient rating one or more
      symptoms on the ESAS >=7 is at high risk of self-defined burden and likely to be
      experiencing significant impact on physical, emotional and social functioning.
      Further work should look at which aspects of symptom management best promote a
      lessening of perceived burden.

PMID- 22145894
TI  - The care of the very old in the last three days of life.
AB  - BACKGROUND: As life expectancy has increased, the age at which people are dying
      has also increased. There is limited knowledge of the experience of dying of the
      very old. We sought to examine the last 3 days of life for the very old, dying in
      a palliative care unit, focusing upon symptom burden and medications prescribed.
      METHODS: A retrospective review of medical records of consecutive patients who
      died in two inpatient palliative care units. Information collated included
      demographic and medical information, symptom data, and medications (opioids,
      benzodiazepines and antipsychotics) administered. Analysis comparing patients
      aged 80 years and older (cases) and those in the median age range of the treating
      palliative care units, that is, those aged 50 to 70 years (comparators) were
      conducted. RESULTS: One hundred five cases and 100 comparators were identified.
      Analysis revealed a significantly shorter length of stay in the cases (13 days)
      compared to comparators (19 days; p<=0.01).) In the last 3 days, cases received
      significantly less parenteral morphine equivalents (82.8 versus 170.5 mg,
      p<0.05), midazolam (12.1 versus 19.1 mg, p<0.05), and lorazepam equivalents (0.9
      versus 2.4 mg, p<0.01). Overall, symptom profiles between the groups were
      similar. IMPLICATIONS: The very old appear to have a distinct experience of
      palliative inpatient care with shorter admissions, and lower requirements for
      medication. Reasons for lower medication requirements are discussed, and the need
      for future prospective studies in this area is highlighted. A better
      understanding of the needs of this population at end of life will enable adequate
      service planning and improved care.

PMID- 22145895
TI  - Emergency department management of hospice patients #246.

PMID- 22145896
TI  - Initiating a hospice referral from the emergency department #247.

PMID- 22145897
TI  - In lieu of flowers....

PMID- 22145901
TI  - "Myeloma has no human face": past, present, and future dignity lessons from
      traffic lines.

PMID- 22145905
TI  - A cohesin-RAD21 interactome.
AB  - The cohesin complex holds the sister chromatids together from S-phase until the
      metaphase-to-anaphase transition, and ensures both their proper cohesion and
      timely separation. In addition to its canonical function in chromosomal
      segregation, cohesin has been suggested by several lines of investigation in
      recent years to play additional roles in apoptosis, DNA-damage response,
      transcriptional regulation and haematopoiesis. To better understand the basis of
      the disparate cellular functions of cohesin in these various processes, we have
      characterized a comprehensive protein interactome of cohesin-RAD21 by using three
      independent approaches: Y2H (yeast two-hybrid) screening, immunoprecipitation
      coupled-MS of cytoplasmic and nuclear extracts from MOLT-4 T-lymphocytes in the
      presence and absence of etoposide-induced apoptosis, and affinity pull-down
      assays of chromatographically purified nuclear extracts from pro-apoptotic MOLT-4
      cells. Our analyses revealed 112 novel protein interactors of cohesin-RAD21 that
      function in different cellular processes, including mitosis, regulation of
      apoptosis, chromosome dynamics, replication, transcription regulation, RNA
      processing, DNA-damage response, protein modification and degradation, and
      cytoskeleton and cell motility. Identification of cohesin interactors provides a
      framework for explaining the various non-canonical functions of the cohesin
      complex.

PMID- 22145906
TI  - Confirmatory method for the determination of streptomycin and dihydrostreptomycin
      in honey by LC-MS/MS.
AB  - A method was specifically developed for the determination and confirmation of
      streptomycin and dihydrostreptomycin in different types of honey. The method is
      simple, rapid, sensitive and was validated for streptomycin and
      dihydrostreptomycin in accordance with Commission Decision 2002/657/EC. After
      extraction with phosphate buffer and a pH change, clean-up was performed via SPE
      with polymeric phase. LC-MS/MS analysis was carried out using two different HILIC
      columns for the separation of the analytes and using a triple quadrupole mass
      spectrometer in positive ESI mode to measure the transitions of the substances in
      MRM mode. For the quantification of both substances, matrix calibration curves in
      a linear range of 5-80 g kg(-1) were used. The validation parameters established
      for streptomycin and dihydrostreptomycin, CCalpha (11.8 and 11.5 ug kg(-1),
      respectively), CCbeta (18.9 and 19.9 ug kg(-1), respectively), recovery (97 and
      101%, respectively) and the relative within-laboratory reproducibility RSD(wR)
      (16.4 and 20.8%, respectively) at the recommended concentration of 40 ug kg(-1),
      fulfil the requirements of Commission Decision 2002/657/EC.

PMID- 22145907
TI  - The S100B protein in biological fluids: more than a lifelong biomarker of brain
      distress.
AB  - S100B is a calcium-binding protein concentrated in glial cells, although it has
      also been detected in definite extra-neural cell types. Its biological role is
      still debated. When secreted, S100B is believed to have paracrine/autocrine
      trophic effects at physiological concentrations, but toxic effects at higher
      concentrations. Elevated S100B levels in biological fluids (CSF, blood, urine,
      saliva, amniotic fluid) are thus regarded as a biomarker of pathological
      conditions, including perinatal brain distress, acute brain injury, brain tumors,
      neuroinflammatory/neurodegenerative disorders, psychiatric disorders. In the
      majority of these conditions, high S100B levels offer an indicator of cell damage
      when standard diagnostic procedures are still silent. The key question remains as
      to whether S100B is merely leaked from injured cells or is released in
      concomitance with both physiological and pathological conditions, participating
      at high concentrations in the events leading to cell injury. In this respect,
      S100B levels in biological fluids have been shown to increase in physiological
      conditions characterized by stressful physical and mental activity, suggesting
      that it may be physiologically regulated and raised during conditions of stress,
      with a putatively active role. This possibility makes this protein a candidate
      not only for a biomarker but also for a potential therapeutic target.

PMID- 22145908
TI  - The roles of child, parent and environmental factors in pedestrian supervision.
AB  - Pedestrian injuries are a significant health risk to children, particularly those
      5-9 years of age. Surprisingly, few studies have explored parent-related factors
      that may moderate this risk. We examined parental supervision choices in the
      context of child pedestrian experience, parent perceptual factors and varying
      levels of environmental risk. A series of street crossing scenarios were used to
      examine the roles of child, parent and environmental factors in determining
      parents' supervision choices. Parents recognised differing levels of risk across
      environmental conditions and altered their supervision choices accordingly. Child
      age and parental risk perception were significantly predictive of supervision
      choices. Our results demonstrate that parents assess multiple factors when
      determining the intensity of supervision necessary for their children. Notably,
      parents adjust their supervision in direct relation to changes in the physical
      environment. Implications of these findings for injury prevention and future
      research are discussed.

PMID- 22145909
TI  - Drug delivery applications for superporous hydrogels.
AB  - INTRODUCTION: Considerable advances have been made to hydrogels with the
      development of faster swelling superporous hydrogels (SPHs). These new-generation
      hydrogels have large numbers of interconnected pores, giving them the capacity to
      absorb large amounts of water at an accelerated rate. This gives SPHs the ability
      to be used in a variety of novel drug delivery applications, such as gastric
      retention and peroral intestinal delivery of proteins and peptides. AREAS
      COVERED: This review focuses on the applications of SPHs for drug transport and
      targeted drug therapies, as well as the characteristics and historical
      advancements made to SPH synthesis as it pertains to drug delivery. Manufacturing
      considerations and challenges that must be overcome are also discussed, such as
      scale-up, biocompatibility and safety. EXPERT OPINION: Modern SPHs have high
      swelling and high mechanical strength making them suitable for many diverse
      pharmaceutical and biomedical applications. However, demonstrative preclinical
      animal studies still need to be confirmed in human trials, to further address
      safety issues and confirm therapeutic success when using SPHs as platforms for
      drug delivery. The focus of forthcoming applications of SPHs is likely to be in
      the area of oral site-specific delivery and regenerative medicine.

PMID- 22145910
TI  - Dynamical properties of alcohol + 1-hexyl-3-methylimidazolium ionic liquid
      mixtures: a computer simulation study.
AB  - In this work, extensive molecular dynamics simulations of the dynamics of
      mixtures of ionic liquids (ILs) composed of the cation 1-hexyl-3
      methylimidazolium and several anions of different hydrophobicity degrees (Cl(-),
      BF(4)(-), PF(6)(-)) with alcohols of different chain lengths (methanol and
      ethanol) are reported. We evaluated the influence of the nature of the anion, the
      length of the molecular chain of the alcohol, and the alcohol concentration on
      some dynamical properties of the mixtures, such as self-diffusion coefficients of
      all the species, mean square displacements (with an analysis of both ballistic
      and diffusive regimes), and velocity autocorrelation functions of alcohol
      molecules. The diffusivity of the mixtures was found to be highly dependent on
      the nature of the anion since the interaction between chloride and alcohols is
      greater than that with fluorinated anions and leads to slower dynamics.
      Additionally, our results show that self-diffusion coefficients increase with
      alcohol concentration. On the other hand, a subdiffusive regime over thousands of
      picoseconds was detected at intermediate times through analysis of the center-of
      mass mean square displacements of alcohol molecules, a region that becomes
      narrower as alcohol concentration increases. Finally, the study of the role of
      the anion and of solvent concentration on velocity autocorrelation functions
      reflects an increase in mean collision times as the amount of alcohol increases
      until the value of pure alcohols is reached. These collision times are smaller in
      mixtures with halogenated ILs.

PMID- 22145911
TI  - Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate
      for the initial treatment of patients with mantle cell lymphoma, a multicentre
      trial from Gruppo Italiano Studio Linfomi.
AB  - This study investigated the clinical activity and toxicity of R-HCVAD-AM
      [rituximab plus HyperCVAD (R-HCVAD) alternating with high-dose cytarabine and
      methotrexate (AM)] in patients with newly diagnosed Mantle Cell Lymphoma (MCL).
      Patients aged <=70years with confirmed MCL received four alternating cycles each
      of R-HCVAD and AM. Patients who obtained a partial response proceeded to
      autologous stem cell transplant. Sixty-three patients were enrolled and 60 were
      fully eligible. Median age was 57years (22-66); 60%, 33% and 7% were classified
      at low (L)-, intermediate (I)- or high (H)-risk, respectively, according to the
      MCL International Prognostic Index (MIPI). Only 22 patients (37%) completed the
      four cycles and three patients died during therapy. Overall response and complete
      response rates were 83% and 72% respectively. After a median follow-up of
      46months (range 1-72) the estimated 5-year overall survival (OS) and progression
      free survival rates were 73% [95% confidence interval (CI) 59-83%], and 61%
      (95%CI 45-73%) respectively. MIPI maintained the prognostic value with an
      estimated 5-year OS of 89%, 80% and 24% for L, I, and H groups respectively
      (P<0.001). This multicentre study confirms that R-HCVAD-AM is an active regimen
      for the initial treatment of patients with MCL, but is associated with
      significant toxicity.

PMID- 22145913
TI  - First robot-assisted thyroidectomy in Japan performed using a standard da Vinci
      surgical system.

PMID- 22145912
TI  - Promoting mobility after hip fracture (ProMo): study protocol and selected
      baseline results of a year-long randomized controlled trial among community
      dwelling older people.
AB  - BACKGROUND: To cope at their homes, community-dwelling older people surviving a
      hip fracture need a sufficient amount of functional ability and mobility. There
      is a lack of evidence on the best practices supporting recovery after hip
      fracture. The purpose of this article is to describe the design, intervention and
      demographic baseline results of a study investigating the effects of a
      rehabilitation program aiming to restore mobility and functional capacity among
      community-dwelling participants after hip fracture. METHODS/DESIGN: Population
      based sample of over 60-year-old community-dwelling men and women operated for
      hip fracture (n = 81, mean age 79 years, 78% were women) participated in this
      study and were randomly allocated into control (Standard Care) and ProMo
      intervention groups on average 10 weeks post fracture and 6 weeks after
      discharged to home. Standard Care included written home exercise program with 5-7
      exercises for lower limbs. Of all participants, 12 got a referral to
      physiotherapy. After discharged to home, only 50% adhered to Standard Care. None
      of the participants were followed-up for Standard Care or mobility recovery.
      ProMo-intervention included Standard Care and a year-long program including
      evaluation/modification of environmental hazards, guidance for safe walking, pain
      management, progressive home exercise program and physical activity counseling.
      Measurements included a comprehensive battery of laboratory tests and self-report
      on mobility limitation, disability, physical functional capacity and health as
      well as assessments for the key prerequisites for mobility, disability and
      functional capacity. All assessments were performed blinded at the research
      laboratory. No significant differences were observed between intervention and
      control groups in any of the demographic variables. DISCUSSION: Ten weeks post
      hip fracture only half of the participants were compliant to Standard Care. No
      follow-up for Standard Care or mobility recovery occurred. There is a need for
      rehabilitation and follow-up for mobility recovery after hip fracture. However,
      the effectiveness of the ProMo program can only be assessed at the end of the
      study. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53680197.

PMID- 22145914
TI  - Alveolar bony crest preservation at implants installed immediately after tooth
      extraction: an experimental study in the dog.
AB  - AIM: To evaluate the influence of deproteinized bovine bone mineral in
      conjunction with a collagen membrane, at implants installed into sockets in a
      lingual position immediately after tooth extraction, and presenting initial
      horizontal residual buccal defects <2 mm. MATERIAL AND METHODS: The pulp tissue
      of the mesial roots of (4)P(4) was removed in six Labrador dogs, and the root
      canals were filled with gutta-percha and cement. Flaps were elevated, and the
      buccal and lingual alveolar bony plates were exposed. The premolars were hemi
      sectioned, and the distal roots were removed. Implants were installed in a
      lingual position and with the margin flush with the buccal bony crest. After
      installation, defects resulted at about 1.7 mm in width at the buccal aspects,
      both at the test and control sites. Only in the left site (test), deproteinized
      bovine bone mineral (DBBM) particles were placed into the defect concomitantly
      with the placement of a collagen membrane. A non-submerged healing was allowed.
      RESULTS: After 3 months of healing, one implant was found not integrated and was
      excluded from the analysis together with the contralateral control implant. All
      remaining implants were integrated into mature bone. The bony crest was located
      at the same level of the implant shoulder, both at the test and control sites. At
      the buccal aspect, the most coronal bone-to-implant contact was located at a
      similar distance from the implant margin at the test (1.7 +/- 1.0 mm) and control
      (1.6 +/- 0.8 mm) sites, respectively. Only small residual DBBM particles were
      found at the test sites. CONCLUSION: The placement of an implant in a lingual
      position into a socket immediately after tooth extraction may favor a low
      exposure of the buccal implant surface. The use of DBBM particles, concomitantly
      with a collagen membrane, did not additionally improve the outcome obtained at
      the control sites.

PMID- 22145915
TI  - Will the implementation of the 2007 National Institute for Health and Clinical
      Excellence (NICE) guidelines on childhood urinary tract infection (UTI) in the UK
      miss significant urinary tract pathology?
AB  - OBJECTIVE: * To investigate whether the implementation of the August 2007
      National Institute for Health and Clinical Excellence (NICE) guidelines would
      miss significant urinary tract pathology in children with urinary tract infection
      (UTI). PATIENTS AND METHODS: * All ultrasound (US) performed in children aged >6
      months, during the year 1 August 2006 to 31 July 2007 for UTI, were
      retrospectively studied. * Each US scan in the study population of 346 was
      categorised dependent on whether it was appropriate or inappropriate to have been
      performed under the new guidelines and whether the US scan was normal or
      abnormal. * The records of each patient with an inappropriate abnormal US scan
      were re-analysed to see if patient management was affected by the US scan. * In
      2011 patients with an original inappropriate abnormal US scan were re-evaluated
      to identify if any had presented with further urinary pathology. RESULTS: * In
      accordance with the NICE guidelines patients were divided by age. * Children aged
      0.5-3 years: 78/95 (82%) US scans were inappropriate of which 12 (15%) were
      abnormal and four of these had a further documented UTI. After careful assessment
      of the US abnormalities it was judged that only one would have benefited from the
      initial US scan. * Children aged >3 years: 146/251 (58%) US scans were
      inappropriate of which 21(14%) were abnormal and six of these (29%) had a further
      documented UTI. After careful assessment of the US abnormalities it was judged
      that only three of 21 (14%) would have benefited from the initial US scan.
      CONCLUSIONS: * The vast majority of anomalies detected on the inappropriate US
      scans were of little clinical significance. * It is difficult to identify any
      patient who would have been truly disadvantaged if the US scan had not been
      performed after the initial UTI. * The NICE guidelines are safe to follow.

PMID- 22145916
TI  - PCR enrichment techniques to identify the diet of predators.
AB  - The increasing sensitivity of PCR has meant that in the last two decades PCR has
      emerged as a major tool in diet studies, enabling us to refine our understanding
      of trophic links and to elucidate the diets of predators whose prey is as yet
      uncharacterized. The achievements and methods of PCR-based diet studies have been
      reviewed several times, but here we review an important development in the field:
      the use of PCR enrichment techniques to promote the amplification of prey DNA
      over that of the predator. We first discuss the success of using group-specific
      primers either in parallel single reactions or in multiplex reactions. We then
      concentrate on the more recent use of PCR enrichment techniques such as
      restriction enzyme digests, peptide nucleic acid clamping, DNA blocking and laser
      capture microdissection. We also survey the vast literature on enrichment
      techniques in clinical biology, to ascertain the pitfalls of enrichment
      techniques and what refinements have yielded some highly sensitive methods. We
      find that while there are several new approaches to enrichment, peptide nucleic
      acid clamping and DNA blocking are generally sufficient techniques for the
      characterization of diets of predators and highlight the most important
      considerations of the approach.

PMID- 22145917
TI  - Frequency and factors influencing publication of abstracts presented at three
      major nephrology meetings.
AB  - BACKGROUND AND OBJECTIVES: There have been no contemporary studies assessing
      abstract publication rates and the factors associated with full publication
      within the field of nephrology. As such, it is unclear whether a publication bias
      exists for abstracts presented at nephrology meetings, which may hinder the
      dissemination of potentially important results. Our objective was to review a
      selection of abstracts presented at 3 major nephrology meetings to determine the
      proportion that reach full publication and factors associated with full
      publication. METHODS: 300 randomly selected abstracts presented as posters at
      three annual nephrology meetings in 2006 [American Society of Nephrology (ASN),
      European Renal Association (ERA), and National Kidney Foundation (NKF)] were
      reviewed. Accepted methods of literature search were performed to determine
      subsequent journal publication. Univariate and multivariate analyses were
      performed to determine the association between abstract characteristics and
      subsequent full publication. RESULTS: 127 (42%) abstracts were published in peer
      reviewed journals at 4.5 years. On multivariable analysis, basic science research
      (OR 2.84, 95% CI 1.44-5.61 as compared to clinical research) and the scientific
      meeting [OR 2.87, 95% CI 1.60-5.15 (ASN); OR 1.92, 95% CI 1.07-3.45(ERA) as
      compared to NKF] were significantly associated with full publication.
      CONCLUSIONS: Almost two-fifths of abstracts presented at three major nephrology
      meetings are subsequently published in peer-reviewed journals. Basic science
      content and the meeting at which the abstract was presented are associated with
      publication. Further research is needed to ascertain the impact of other
      important factors on abstract publication rates to address publication bias in
      the renal literature.

PMID- 22145918
TI  - Amine-functionalized lanthanide-doped KGdF4 nanocrystals as potential
      optical/magnetic multimodal bioprobes.
AB  - Amine-functionalized lanthanide-doped KGdF(4) nanocrystals, synthesized via a
      facile one-step solvothermal route by employing polyethylenimine as the
      surfactant and capping ligand, have been demonstrated to be sensitive time
      resolved FRET bioprobes to detect a trace amount of biomolecules such as avidin
      at a concentration of 5.5 nM and to be potential T(1)-MRI contrast agents due to
      a large longitudinal relaxivity of Gd(3+) (5.86 S(-1).mM(-1) per Gd ion and 3.99
      * 10(5) S(-1).mM(-1) per nanocrystal).

PMID- 22145920
TI  - NK1.1(+)  cells regulate neutrophil migration in mice with Acinetobacter
      baumannii pneumonia.
AB  - Acinetobacter baumannii is a major cause of both community-associated and
      nosocomial infections worldwide. These infections are difficult to treat because
      the bacterium rapidly develops resistance to multiple antibiotics. However,
      little is known about the nature of the innate cellular response to A. baumannii
      infection. In the present study, we identified the cells infiltrating the lungs
      of mice with Acinetobacter pneumonia and analyzed their response to infection.
      Normal mice eradicated the A. baumannii infection within 3 days of inoculation.
      Neutrophils were rapidly recruited to the lungs, followed by macrophages and
      NK1.1(+)  cells. Neutrophil-depleted mice showed acute and severe symptoms, and
      all of the mice died within 3 days of inoculation. The majority of macrophage
      depleted mice responded in a similar manner to the control mice. These results
      indicate that neutrophils are essential for the elimination of A. baumannii. Half
      of NK1.1(+)  cell-depleted mice died within 1 day of inoculation and the number
      of infiltrating neutrophils was lower than that in control mice up until 3 days
      post-inoculation. Moreover, the expression levels of keratinocyte chemoattractant
      protein (KC) decreased in NK1.1(+)  cell-depleted mice. These results indicate
      that NK1.1(+)  cells recruit neutrophils during the early phase of Acinetobacter
      infection by increasing KC expression.

PMID- 22145921
TI  - Erythropoietin attenuates the sequels of ischaemic spinal cord injury with
      enhanced recruitment of CD34+ cells in mice.
AB  - Erythropoietin has been shown to promote tissue regeneration after ischaemic
      injury in various organs. Here, we investigated whether Erythropoietin could
      ameliorate ischaemic spinal cord injury in the mouse and sought an underlying
      mechanism. Spinal cord ischaemia was developed by cross-clamping the descending
      thoracic aorta for 7 or 9 min. in mice. Erythropoietin (5000 IU/kg) or saline was
      administrated 30 min. before aortic cross-clamping. Neurological function was
      assessed using the paralysis score for 7 days after the operation. Spinal cords
      were histologically evaluated 2 and 7 days after the operation.
      Immunohistochemistry was used to detect CD34(+)  cells and the expression of
      brain-derived neurotrophic factor and vascular endothelial growth factor. Each
      mouse exhibited either mildly impaired function or complete paralysis at day 2.
      Erythropoietin-treated mice with complete paralysis demonstrated significant
      improvement of neurological function between day 2 and 7, compared to saline
      treated mice with complete paralysis. Motor neurons in erythropoietin-treated
      mice were more preserved at day 7 than those in saline-treated mice with complete
      paralysis. CD34(+)  cells in the lumbar spinal cord of erythropoietin-treated
      mice were more abundant at day 2 than those of saline-treated mice. Brain-derived
      neurotrophic factor and vascular endothelial growth factor were markedly
      expressed in lumbar spinal cords in erythropoietin-treated mice at day 7.
      Erythropoietin demonstrated neuroprotective effects in the ischaemic spinal cord,
      improving neurological function and attenuating motor neuron loss. These effects
      may have been mediated by recruited CD34(+)  cells, and enhanced expression of
      brain-derived neurotrophic factor and vascular endothelial growth factor.

PMID- 22145922
TI  - Downregulating hypoxia-inducible factor-2alpha improves the efficacy of
      doxorubicin in the treatment of hepatocellular carcinoma.
AB  - The hypoxic microenvironment inside solid tumors, including hepatocellular
      carcinoma (HCC), is a major cause of tumor resistance to chemotherapy. The
      recently identified hypoxia-inducible factor (HIF)-2 executes the hypoxia
      response. Its expression feature and transcriptional targets indicate a possible
      dominance of HIF-2 in regulating genes in HCC. The aim of the present study was
      to determine whether transfection of siRNA targeting HIF-2alpha could enhance the
      efficacy of doxorubicin, the most commonly used drug in the treatment of HCC.
      Transfection of HIF-2 siRNA into human HCC cells downregulated the expression of
      HIF-2alpha, vascular endothelial growth factor (VEGF), transforming growth factor
      (TGF)-alpha, and cyclin D1, but had little effect on the expression of HIF
      1alpha, fms-related tyrosine kinase-1 (Flt-1), the glucose transporter (GLUT)-1,
      and lactate dehydrogenase A (LDHA). Doxorubicin itself only downregulated VEGF
      expression. Furthermore, HIF-2 siRNA inhibited proliferation, induced cell cycle
      arrest at the G(0)/G(1) phase, and acted synergistically with doxorubicin to
      inhibit the growth of human HCC cells in vitro. Transfection of HIF-2 siRNA also
      downregulated tumoral expression of HIF-2alpha, VEGF, TGF-alpha, and cyclin D1 in
      vivo, and acted synergistically with doxorubicin to suppress the growth of HepG2
      tumors established in immunodeficient mice by inhibiting cell proliferation,
      tumor angiogenesis and microvessel perfusion. The results of the present study
      suggest that targeting HIF-2alpha with siRNA warrants investigation as a
      potential strategy to enhance the efficacy of doxorubicin in the treatment of
      HCC.

PMID- 22145924
TI  - Hybrid polyoxovanadates: anion-influenced formation of nanoscopic cages and
      supramolecular assemblies of asymmetric clusters.
AB  - Two novel hybrid polyoxovanadates that are functionalized by (4
      aminophenyl)arsonic acid ligands form upon the reduction of vanadates(V) in
      aqueous systems, whereby the underlying condensation reactions are influenced by
      the nature of the employed acid. In the presence of Cl(-) ions that derive from
      hydrochloric acid, a tetradecanuclear cage structure [V(IV)(14)O(16)(OH)(8)
      (O(3)AsC(6)H(4)-4-NH(2))(10)](4-), whose cavity contains stabilizing halide ions
      and water molecules, is obtained. When nitric acid is used, a decanuclear
      [V(10)O(18)(O(3)AsC(6)H(4)-4-NH(2))(7)(DMF)(2)](5-) cluster can be isolated. The
      latter organizes into a hexagonal packing arrangement in the solid state.

PMID- 22145923
TI  - Low doses of selenium specifically stimulate the repair of oxidative DNA damage
      in LNCaP prostate cancer cells.
AB  - Epidemiological studies have demonstrated an inverse relationship between
      selenium (Se) intake and cancer incidence and/or mortality. However, the
      molecular mechanisms underlying the cancer chemopreventive activity of Se
      compounds remain largely unknown. The objective of this study was to investigate
      the effect of low doses of Se on the stimulation of DNA repair systems in
      response to four different qualities of DNA damage. P53-proficient LNCaP human
      prostate adenocarcinoma cells were grown either untreated or in the presence of
      low concentrations of two Se compounds (30 degrees  nM sodium selenite, or 10 MUM
      selenomethionine) and exposed to UVA, H2O2, methylmethane sulfonate (MMS) or UVC.
      Cell viability as well as DNA damage induction and repair were evaluated by the
      alkaline Comet assay. Overall, Se was shown to be a very potent protector against
      cell toxicity and genotoxicity induced by oxidative stress (UVA or H2O2) but not
      from the agents that induce other types of deleterious lesions (MMS or UVC).
      Furthermore, Se-treated cells exhibited increased oxidative DNA repair activity,
      indicating a novel mechanism of Se action. Therefore, the benefits of Se could be
      explained by a combination of antioxidant activity, the reduction in DNA damage
      and the enhancement of oxidative DNA repair capacity.

PMID- 22145925
TI  - Psychological symptom patterns and vital exhaustion in outpatients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Several studies have reported high prevalence of anxiety and
      depression in chronic obstructive pulmonary disease (COPD) outpatients. Moreover,
      these patients share psychological or psychopathological characteristics that
      inhibit their ability to cope with the disease. In the present study we aimed to
      record the prevalence of psychological symptom patterns in a sample of Greek COPD
      outpatients and to assess which psychological factors (and to which degree)
      contribute to vital exhaustion (VE). METHODS: The study included 139 COPD
      outpatients. We used the Symptom Checklist 90 - Revised (SCL-90-R) and the
      Maastricht Questionnaire (MQ) in order to evaluate psychological symptom patterns
      and VE, respectively. RESULTS: The mean MQ score was 19.6, which is significantly
      higher than the corresponding score in the general population. Regarding the SCL
      90-R dimensions, depression was the highest followed by somatization, obsessive
      compulsive and anxiety dimensions. Additionally, a positive correlation was
      observed between the MQ and the SCL-90-R dimensions. MQ failed to demonstrate
      correlation with age, gender, education level or the severity of the disease.
      Depression seems to be responsible for 57.9% of the variation of VE, while
      obsessive-compulsiveness is responsible for an additional 2.4%. All the remaining
      dimensions of SCL-90-R had no statistically significant contributions.
      CONCLUSIONS: Our findings suggest the high prevalence of VE, together with high
      rates in most of the SCL-90-R dimensions with greater depression, somatization,
      obsessive-compulsiveness and anxiety in a Greek COPD group at various Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria
      stages. The coexistence of such symptoms should be further assessed as an
      eventual unfavorable prognostic factor.

PMID- 22145926
TI  - A quantitative description of the peptide sharing between poliovirus and Homo
      sapiens.
AB  - In the present study, we analyze the peptide commonality between poliovirus
      polyprotein and the human proteins. We report on the following findings: (1) the
      extent of polio peptide overlap on the human proteome is high, and involves the
      entire viral polyprotein; (2) viral peptide matching affects human proteins
      linked to fundamental cellular functions. The data may help to further our
      understanding of the relationships between poliovirus and the human host.

PMID- 22145927
TI  - A missing error term in benefit-cost analysis.
AB  - Benefit-cost models are frequently used to inform environmental policy and
      management decisions. However, they typically omit a random or pure error which
      biases downward any estimated forecast variance. Ex-ante benefit-cost analyses
      create a particular problem because there are no historically observed values of
      the dependent variable, such as net present social value, on which to construct a
      historically based variance as is the usual statistical approach. To correct this
      omission, an estimator for the random error variance in this situation is
      developed based on analysis of variance measures and the coefficient of
      determination, R(2). A larger variance may affect decision-maker's choices if
      they are risk averse, consider confidence intervals, exceedance probabilities, or
      other measures related to the variance. When applied to a model of the net
      benefits of the Clean Air Act, although the probability of large net benefits
      increases, the probability that the net present value is negative also increases
      from 0.2 to 4.5%. A framework is also provided to assist in determining when a
      variance estimate would be better, in a utility sense, than using the current
      default of a zero error variance.

PMID- 22145928
TI  - Estimation of furan contamination across the Belgian food chain.
AB  - This paper provides an estimate of the furan content of Belgian foods. The
      objective of the study was to achieve the best food chain coverage with a
      restricted number of samples (n = 496). The geographic distribution, different
      market chains and labels, and consumption frequencies were taken into account in
      the construction of the sampling plan. Weighting factors such as contamination
      levels, consumption frequency and the diversity of food items were applied to set
      up the model. The very low detection capabilities (CC(beta)) of the analytical
      methods used (sub-ppb) allowed reporting of 78.2% of the overall dataset above
      CC(beta) and, in particular, 96.7% for the baby food category. The highest furan
      levels were found in powdered roasted bean coffee (1912 ug kg(-1)) with a mean of
      756 ug kg(-1) for this category. Prepared meat, pasta and rice, breakfast
      cereals, soups, and baby food also showed high mean furan contents ranging from
      16 to 43 ug kg(-1). Comparisons with contamination surveys carried out in other
      countries pointed out differences for the same food group and therefore
      contamination levels are related to the geographical origin of food items.

PMID- 22145930
TI  - Support for breaking the nexus between alcohol and community sports settings:
      findings from the VicHealth Community Attitudes Survey in Australia.
AB  - INTRODUCTION AND AIMS: This study describes levels and predictors of community
      attitudes towards alcohol, support for structural alterations to the drinking
      context, and intention to increase participation in community sports clubs.
      DESIGN AND METHODS: Cross-sectional data were obtained from the VicHealth
      Community Attitudes Survey on Healthy Sporting Environments, administered to a
      random sample of Victorian adults. Descriptive and multivariate logistic
      regression analysis was undertaken. RESULTS: Very high support for removing
      alcohol sponsorship of community sport and for a levy on alcohol advertising was
      found. The groups most supportive of breaking the nexus between alcohol and
      community sport were female, older-aged and non-English-speaking citizens and
      those not involved in sport clubs. If alcohol sales at community sports clubs
      were reduced, participation may increase among population groups currently
      identified as least engaged with community sport. DISCUSSION AND CONCLUSIONS: An
      optimal climate exists for policy reforms to make community sporting environments
      healthier by reducing the ties with alcohol. If implemented, these reforms may
      lead to an increase and diversification of participants in community sport.

PMID- 22145929
TI  - Post-translational modifications of the serotonin type 4 receptor heterologously
      expressed in mouse rod cells.
AB  - G-protein-coupled serotonin receptor type 4 (5-HT(4)R) is a pharmacological
      target implicated in a variety of gastrointestinal and nervous system disorders.
      As for many other integral membrane proteins, structural and functional studies
      of this receptor could be facilitated by its heterologous overexpression in
      eukaryotic systems that can perform appropriate post-translational modifications
      (PTMs) on the protein. We previously reported the development of an expression
      system that employs rhodopsin's biosynthetic machinery in rod cells of the retina
      to express heterologous G-protein-coupled receptors (GPCRs) in a
      pharmacologically functional form. In this study, we analyzed the glycosylation,
      phosphorylation, and palmitoylation of 5-HT(4)R heterologously expressed in rod
      cells of transgenic mice. We found that the glycosylation pattern in 5-HT(4)R was
      more complex than in murine and bovine rhodopsin. Moreover, overexpression of
      this exogenous GPCR in rod cells also affected the glycosylation pattern of
      coexisting native rhodopsin. These results highlight not only the occurrence of
      heterogeneous PTMs on transgenic proteins but also the complications that non
      native PTMs can cause in the structural and functional characterization of both
      endogenous and heterologous protein targets.

PMID- 22145931
TI  - Predictors of functional outcome after right hemisphere stroke in patients with
      or without thrombolytic treatment.
AB  - The purpose of this study was to assess the predictors of functional outcome
      after right hemisphere stroke at 6-month follow up in patients with or without
      thrombolytic treatment. Thrombolysis did not predict functional outcome in
      instrumental activities of daily living (IADL). Lower acute phase basic
      activities of daily living (ADL) measured by the Barthel Index was a
      statistically significant predictor of IADL when adjusted for age and education
      (p = .015) and had borderline significance (p = .076) as a predictor of
      functional outcome when adjusted for severity of stroke at admission. When stroke
      severity was taken into account also higher age became a statistically
      significant (p = .039) predictor of functional outcome. The acute phase
      neuropsychological symptoms predicted the functional outcome in unadjusted
      analyses but when adjusted for age, education, and severity of stroke no
      independent association was found.

PMID- 22145932
TI  - Melt extrusion: process to product.
AB  - INTRODUCTION: Niche applicability and industrial adaptability have led hot melt
      extrusion (HME) techniques to gain wide acceptance and have, therefore,
      solidified their place in the array of pharmaceutical research and manufacturing
      operations. Melt extrusion's momentum has resulted in extensive research
      publications, reviews and patents on the subject for over a decade. Currently, >
      50% of the new drug candidates are speculated to be highly lipophilic and thus
      poorly bioavailable. HME is a key technology for these and other formulation and
      processing issues. AREAS COVERED: Various approaches have been addressed using
      HME in developing solid molecular dispersions and have demonstrated viability to
      provide sustained, modified and targeted drug delivery resulting in improved
      bioavailability. This review provides a holistic perspective on HME from
      equipment, processing and materials to its varied applications in oral delivery
      (immediate release, sustained release, taste masking, enteric and targeted
      release, as well as trans-drug delivery), oral mucosal, dermal, ungual and
      intravaginal systems. EXPERT OPINION: Interest in HME as a pharmaceutical process
      continues to grow and the potential of automation and reduction of capital
      investment and labor costs has earned this technique a necessary consideration as
      a drug delivery solution.

PMID- 22145934
TI  - Structural investigation of nonionic fluorinated micelles by SANS in relation to
      mesoporous silica materials.
AB  - In an attempt to answer the question if there is dependence between the pore
      ordering of the mesoporous silica, obtained through the cooperative template
      mechanism, and the shape of the micellar aggregates of the surfactant solutions,
      the micellar structures of two nonionic fluorinated surfactant based-systems are
      studied by SANS. By fitting the experimental spectra with theoretical models, the
      structural evolution of the molecular aggregates can be described, and some
      important parameters can be obtained, such as the water and eventually oil
      penetration into the surfactant film, the aggregation number, the area per polar
      head of the surfactant, and the surfactant chain conformations. We have shown
      that for the C(8)F(17)C(2)H(4)(OC(2)H(4))(9)OH system, the micelles are prolate
      spheroids. The increase of the surfactant concentration in water does not change
      the characteristics of the interfacial film, but the aggregation number raises
      and the particles become more elongated. By contrast, the experimental curves of
      C(7)F(15)C(2)H(4)(OC(2)H(4))(8)OH cannot be fitted considering a small particle
      model. However, progressive incorporation of fluorocarbon induces a change of
      size and shape of the globules, which become smaller and more and more spherical.
      Regarding the material mesopore ordering, it appears that the micelles that lead
      to hexagonal mesoporous silica materials are described with a model of quasi
      spherical globules. On the contrary, when large micelles are found, only wormhole
      like structures are obtained.

PMID- 22145933
TI  - Serum leptin level mediates the association of body composition and serum C
      reactive protein in HIV-infected persons on antiretroviral therapy.
AB  - Higher body mass index (BMI) is associated with increased serum C-reactive
      protein (CRP) levels in HIV-infected individuals on antiretroviral therapy (ART),
      but the relationship of adipose tissue mass to systemic inflammation is not well
      described in this population. We hypothesized that serum adipokine levels (i.e.,
      hormones produced by adipocytes) are a superior predictor of CRP compared to
      anthropometric or radiographic measures of body composition in patients on
      effective, stable ART. We evaluated the relationship of serum leptin,
      adiponectin, and resistin, BMI, and dual energy x-ray absorptiometry (DEXA)
      measurements with serum highly sensitive CRP (hsCRP) in a cross-sectional cohort
      of 106 predominantly virologically suppressed, HIV-infected adults on ART for
      >=24 weeks using multivariable linear regression and formal criteria to assess
      statistical mediation. Median BMI, hsCRP, and leptin values were 25.2 kg/m(2),
      3.0 mg/liter, and 3.8 ng/ml, respectively. BMI and DEXA limb fat, body fat, and
      trunk fat measurements were significantly associated with both serum leptin and
      hsCRP levels (all p<=0.02). Leptin was also associated with hsCRP (p<0.01). The
      regression coefficient for the effect of BMI or DEXA measurements on hsCRP was
      reduced, and the relationship was no longer statistically significant, after
      adjusting for leptin, indicating leptin functioned as a mediating variable within
      these relationships. Adiponectin and resistin levels did not demonstrate similar
      effects. Serum leptin was a superior predictor of hsCRP compared to BMI and DEXA
      body fat measurements, which may reflect alterations in body composition in
      treated HIV infection and the important contribution of adipose tissue to
      inflammation in this population.

PMID- 22145935
TI  - The prion protein unstructured N-terminal region is a broad-spectrum molecular
      sensor with diverse and contrasting potential functions.
AB  - The physiological function of the prion protein (PrP(C) ) and its conversion into
      its infectious form (PrP(Sc) ) are central issues to understanding the
      pathogenesis of prion diseases. The N-terminal moiety of PrP(C) (NH(2) -PrP(C) )
      is an unstructured region with the characteristic of interacting with a broad
      range of partners. These interactions endow PrP(C) with multifunctional and
      sometimes contrasting capabilities, including neuroprotection and neurotoxicity.
      Recently, binding of beta-sheet rich conformers to NH(2) -PrP(C) demonstrated a
      probable neurotoxic function for PrP(C) in Alzheimer's disease. NH(2) -PrP(C)
      also enhances the propagation of prions in vivo and is the target of the most
      potent antiprion compounds. Another level of complexity is provided by
      endoproteolysis and release of most of NH(2) -PrP(C) into the extracellular
      space. Further studies will be necessary to understand how NH(2) -PrP(C)
      regulates the physiological function of PrP(C) and how it is involved in the
      corruption of its normal function in diseases.

PMID- 22145937
TI  - Multiplexed microsatellite markers for genetic studies of beech.
AB  - European beech (Fagus sylvatica L.) is one of the economically most important
      broadleaved tree species in Europe and has become a model for studying climate
      change effects on forests. Multiplex PCR of microsatellites is a fast and cost
      effective technique allowing high-throughput genotyping. Here we present the
      procedure used to develop two multiplex kits (8-plexes) for European beech. We
      paid particular attention to quality control throughout all steps of the
      multiplex kits development (null allele detection, error rate measurements,
      linkage disequilibrium). Preliminary assays suggest that the 16 amplified loci
      are largely devoid of null alleles and allow rapid and cost-effective genotyping
      of beech with low error rates. The two kits, which differ in their levels of
      polymorphism, most likely due to marker origin, were also informative in seven
      other beech species tested.

PMID- 22145936
TI  - Validation of a susceptibility, benefits, and barrier scale for mammography
      screening among Peruvian women: a cross-sectional study.
AB  - BACKGROUND: Perceived beliefs about breast cancer and breast cancer screening are
      important predictors for mammography utilization. This study adapted and
      validated the Champion's scale in Peru. This scale measures perceived
      susceptibility for breast cancer and perceived benefits and barriers for
      mammography. METHODS: A cross-sectional study was conducted among women ages 40
      to 65 attending outpatient gynecology services in a public hospital in Peru. A
      group of experts developed and pre-tested a Spanish version of the Champion's
      scale to assess its comprehensibility (N=20). Factor analysis, internal
      consistency, and test-retest reliability analyses were performed (N=285).
      Concurrent validity compared scores from participants who had a mammogram and
      those who did not have it in the previous 15 months. T-test and multiple
      regression analysis adjusting for socio-demographic factors, mammography
      knowledge and other preventive behaviors were performed. RESULTS: The construct
      validity and reliability were optimal. Cronbach-Alpha coefficients were 0.75
      (susceptibility), 0.72 (benefits) and 0.86 (barriers). Concurrent validity
      analysis showed an association between barriers and mammography screening use in
      bivariate (22.3+/-6.7 vs. 30.2+/-7.6; p<0.001) and multiple regression analysis
      (OR=0.28, 95% CI=0.18-0.43). Ages 50-60 years (OR=2.35, 95% CI=1.19-4.65),
      history of prior Papanicolaou test (OR=3.69, 95% CI=1.84-7.40), and knowledge
      about breast cancer and mammography (OR=3.69, 95% CI=1.84-7.40) were also
      independently associated with mammography screening use. CONCLUSION: Concurrent
      validity analysis showed that the Champion's scale has important limitations for
      assessing perceived susceptibility for breast cancer and perceived benefits for
      mammography among Peruvian women. There is still a need for developing valid and
      reliable instruments for measuring perceived beliefs about breast cancer and
      mammography screening among Peruvian women.

PMID- 22145938
TI  - Acute effects of muscular counterpulsation therapy on cardiac output and safety
      in patients with chronic heart failure.
AB  - Our aim was to investigate acute effects of muscular counterpulsation (MCP) on
      hemodynamic parameters and to evaluate its safety in regard to myocardial
      integrity and interferences with implanted rhythm devices in patients with
      chronic heart failure (CHF). A total of 22 patients with CHF (16 male, 67.8 +/-
      9.5 years, New York Heart Association [NYHA] class II + III, left ventricular
      ejection fraction 29.6 +/- 6.6%) were treated with MCP for 3 consecutive days for
      45 min, while hemodynamic parameters were measured noninvasively by bioimpedance
      (Task Force Monitor). Laboratory control and a complete device testing were
      performed prior to the first and after the third treatment. In addition,
      continuous rhythm device interrogation was performed online during the first MCP
      application. During each application, a significant increase in cardiac output
      (CO; average change +2.08 +/- 2.33 L/min, P < 0.05) was documented. This increase
      was due to a decrease of total peripheral resistance (-336 +/- 530 dyn * s/cm(5)
      , P < 0.05), to an augmented stroke volume (+8.35 +/-  20.86 mL, P = n.s.), and
      an increase in heart rate (+17.12 +/- 21.12 bpm, P < 0.05). Cardiac markers and
      enzymes were within normal limits at all times and did not increase during
      treatment. MCP stimuli were monitored using surface electrocardiogram, and no
      abnormal sensing or pacing events occurred. MCP acutely improves CO in patients
      with stable CHF. No adverse influence on myocardial integrity was observed nor
      were any inappropriate sensing or pacing artifacts detected in patients with
      implanted rhythm devices.

PMID- 22145939
TI  - Lateral ridge augmentation using a PCL-TCP scaffold in a clinically relevant but
      challenging micropig model.
AB  - BACKGROUND: In implant dentistry, there is a need for synthetic bone substitute
      blocks to support ridge augmentation in situations where large bone volumes are
      missing. Polycaprolactone-based scaffolds demonstrated excellent results in bone
      tissue engineering applications. The use of customized polycaprolactone
      tricalcium phosphate (PCL-TCP) displayed promising results from recent rat femur
      and rabbit calvaria studies. However, data from clinically representative models
      in larger animals do not exist. OBJECTIVE: To evaluate new bone formation in
      association with a novel PCL-TCP scaffold in comparison with an autogenous bone
      block graft for the reconstruction of large dentoalveolar defects in a clinically
      relevant but challenging pig jaw model. MATERIAL AND METHODS: Chronic, non
      contained one-wall defects were created in the mandible of micropigs and randomly
      assigned to receive one of the following guided bone regeneration (GBR)
      procedures for a period of 6 months. (A) Collagen membrane + autogenous block
      graft or (B) Collagen membrane + PCL-TCP scaffold. Micro computed tomography (MU
      CT), histology and histomorphometry were used to assess new bone formation.
      RESULTS: Although MU-CT and histomorphometric analysis demonstrated a slight
      discrepancy between the measurements, the group utilizing autogenous bone grafts
      consistently reported superior new bone formation as compared to PCL-TCP
      scaffolds. When measured using MU-CT, the ratio of bone volume fraction for PCL
      TCP scaffolds with respect to autografts yielded a mean efficacy of approximately
      51%. Histological examination revealed that under favorable conditions, the new
      bone matrix and new bone marrow were in direct contact with the PCL-TCP scaffold
      rods and invading the interstices, suggesting good biocompatibility and high
      osteoconductivity. Autograft block grafts demonstrated 48.5-57.4% of pronounced
      resorption after 6 months following ridge augmentation. CONCLUSIONS: PCL-TCP
      scaffolds have demonstrated the potential application for lateral ridge
      augmentation following a healing period of 6 months in a micropig model.

PMID- 22145940
TI  - Protein kinase C inhibitor prevents renal apoptotic and fibrotic changes in
      response to partial ureteric obstruction.
AB  - What's known on the subject? and What does the study add? Protein kinase C
      inhibitor (PKCI) can decrease glomerular and tubular cell apoptosis and mitosis
      and attenuate collagen accumulation and fibronectin expression in a PUUO rat
      model. Although the role of PKC has been well studied in diabetic nephropathy,
      there is no report on its role in obstructive nephropathy. This investigation
      evaluated the processes that were associated with the activation of PKCalpha and
      PKCbeta pathways and showed that PKCI played an important role in the protection
      of renal function during ureteric obstruction. OBJECTIVES: * To investigate the
      expression of the protein kinase C (PKC) pathway after partial unilateral
      ureteric obstruction (PUUO). * To evaluate the therapeutic potential of a PKC
      inhibitor (PKCI) in obstructive nephropathy. MATERIALS AND METHODS: * Thirty-six
      rats were divided into three groups. One sham-operated group served as the
      control. The other two groups received PUUO surgery, after which one group
      received no treatment and the other group was treated with PKCI, chelerythrine. *
      The severity of hydronephrosis and renal morphology were assessed: tubular and
      glomerularcell apoptosis, mitosis and interstitial fibrosis were examined using
      immunohistochemistry. * Western immunoblots were performed to determine
      fibronectin, transforming growth factor-beta (TGF-beta), and PKC isoform levels.
      RESULTS: * Two weeks after PUUO surgery, hydronephrosis progressively developed.
      Tubular-interstitial fibrosis, collagen deposition and fibronectin expression
      were increased. * PUUO also activated the expression of PKCalpha and PKCbeta and
      the translocation of PKCs from cell cytosol to cell membranes. * Treatment with
      PKCI significantly decreased PKCalpha and PKCbeta expression and translocation in
      the renal cortex. * Treatment with PKCI also reduced the severity of
      hydronephrosis, decreased both glomerular and tubular cell apoptosis and mitosis,
      and attenuated the collagen and fibronectin accumulation in renal interstitium.
      CONCLUSIONS: * Renal tubular apoptosis and interstitial fibrosis after
      obstructive nephropathy are associated with PKCalpha and PKCbeta activation. *
      The PKCI, chelerythrine, is capable of decreasing PKC expression and
      translocation in the renal cortex, suggesting that this inhibitor may have
      therapeutic potential in the protection of renal function in the first few weeks
      after PUUO surgery.

PMID- 22145941
TI  - A household-level sweet potato-based infant food to complement vitamin A
      supplementation initiatives.
AB  - Vitamin A deficiency (VAD) prevalence in Sub-Saharan Africa is high in spite of
      vitamin A supplementation programmes among children in most countries. Plant
      based complementary foods remain the key source of nutrients in addition to
      breast milk for infants in lower income countries. Cereal-legume blends are
      superior in protein and energy densities compared with maize, millet or sorghum
      only porridge. However, unfortified cereal-legume and cereal-only porridges are
      low in vitamin A. A household-level sweet potato-based infant food, rich in
      vitamin A, has been developed to complement vitamin A supplementation initiatives
      in Sub-Saharan Africa. A composite flour containing sweet potato, soybean,
      soybean oil and fishmeal was processed as complementary food by oven toasting
      (denoted oven-toasted ComFa). The oven-toasted ComFa and enriched Weanimix
      (processed from dehulled maize, dehulled soybean, groundnut and fishmeal) were
      assessed for suitability as complementary food based on the nutrient composition
      using specifications in the Codex Standard (CS) as a reference. The sweet potato
      based formulation and enriched Weanimix met the energy, protein, fructose and fat
      specifications but barely met the amino acid score as indicated in the CS.
      However, only the oven-toasted ComFa met the calcium and almost half the vitamin
      A levels as specified in the CS. Oven-toasted ComFa was slightly lower in energy,
      protein and fat by a difference not greater than 4.0% but was higher by more than
      100% in fructose and vitamin A levels. Therefore, the sweet potato-based
      complementary food is likely to support vitamin A supplementation initiatives in
      low-income countries better than the cereal-based formulation.

PMID- 22145942
TI  - Pyrosequencing of BRAF V600E in routine samples of hairy cell leukaemia
      identifies CD5+ variant hairy cell leukaemia that lacks V600E.

PMID- 22145943
TI  - Comparison of diagnostic tests for the detection of Brucella spp. in camel sera.
AB  - BACKGROUND: Brucellosis in livestock causes enormous losses for economies of
      developing countries and poses a severe health risk to consumers of dairy
      products. Little information is known especially on camel brucellosis and its
      impact on human health. For surveillance and control of the disease, sensitive
      and reliable detection methods are needed. Although serological tests are the
      mainstay of diagnosis in camel brucellosis, these tests have been directly
      transposed from cattle without adequate validation. To date, little information
      on application of real-time PCR for detection of Brucella in camel serum is
      available. Therefore, this study was performed to compare the diagnostic
      efficiency of different serological tests and real-time PCR in order to identify
      the most sensitive, rapid and simple combination of tests for detecting Brucella
      infection in camels. FINDINGS: A total of 895 serum samples collected from
      apparently healthy Sudanese camels was investigated. Sudan is a well documented
      endemic region for brucellosis with cases in humans, ruminants, and camels. Rose
      Bengal Test (RBT), Complement Fixation Test (CFT), Slow Agglutination Test (SAT),
      Competitive Enzyme Linked Immunosorbant Assay (cELISA) and Fluorescence
      Polarization Assay (FPA) as well as real-time PCR were used. Our findings
      revealed that bcsp31 kDa real-time PCR detected Brucella DNA in 84.8% (759/895)
      of the examined samples, of which 15.5% (118/759) were serologically negative.
      Our results show no relevant difference in sensitivity between the different
      serological tests. FPA detected the highest number of positive cases (79.3%)
      followed by CFT (71.4%), RBT (70.7%), SAT (70.6%) and cELISA (68.8%). A
      combination of real-time PCR with one of the used serological tests identified
      brucellosis in more than 99% of the infected animals. 59.7% of the examined
      samples were positive in all serological tests and real-time PCR. A subpopulation
      of 6.8% of animals was positive in all serological tests but negative in real
      time PCR assays. The high percentage of positive cases in this study does not
      necessarily reflect the seroprevalence of the disease in the country but might be
      caused by the fact that the camels were imported from brucellosis infected herds
      of Sudan, accidentally. Seroprevalence of brucellosis in camels should be
      examined in confirmatory studies to evaluate the importance of brucellosis in
      this animal species. CONCLUSION: We suggest combining bcsp31 real-time PCR with
      either FPA, CFT, RBT or SAT to screen camels for brucellosis.

PMID- 22145944
TI  - Equilibrium isotope effects on noncovalent interactions in a supramolecular host
      guest system.
AB  - The self-assembled supramolecular complex [Ga(4)L(6)](12-) (1; L = 1,5-bis[2,3
      dihydroxybenzamido]naphthalene) can act as a molecular host in aqueous solution
      and bind cationic guest molecules to its highly charged exterior surface or
      within its hydrophobic interior cavity. The distinct internal cavity of host 1
      modifies the physical properties and reactivity of bound guest molecules and can
      be used to catalyze a variety of chemical transformations. Noncovalent host-guest
      interactions in large part control guest binding, molecular recognition and the
      chemical reactivity of bound guests. Herein we examine equilibrium isotope
      effects (EIEs) on both exterior and interior guest binding to host 1 and use
      these effects to probe the details of noncovalent host-guest interactions. For
      both interior and exterior binding of a benzylphosphonium guest in aqueous
      solution, protiated guests are found to bind more strongly to host 1 (K(H)/K(D) >
      1) and the preferred association of protiated guests is driven by enthalpy and
      opposed by entropy. Deuteration of guest methyl and benzyl C-H bonds results in a
      larger EIE than deuteration of guest aromatic C-H bonds. The observed EIEs can be
      well explained by considering changes in guest vibrational force constants and
      zero-point energies. DFT calculations further confirm the origins of these EIEs
      and suggest that changes in low-frequency guest C-H/D vibrational motions (bends,
      wags, etc.) are primarily responsible for the observed EIEs.

PMID- 22145945
TI  - Circles of care: a novel tool for interprofessional health education.

PMID- 22145946
TI  - Quercetin offers cardioprotection against progression of experimental autoimmune
      myocarditis by suppression of oxidative and endoplasmic reticulum stress via
      endothelin-1/MAPK signalling.
AB  - In order to test the hypothesis that treatment with quercetin at a dose of 10
      mg/kg protects from the progression of experimental autoimmune myocarditis (EAM)
      to dilated cardiomyopathy (DCM), we have used the rat model of EAM induced by
      porcine cardiac myosin. Our results identified that the post-myocarditis rats
      suffered from elevated endoplasmic reticulum (ER) stress and adverse cardiac
      remodelling in the form of myocardial fibrosis, whereas the rats treated with
      quercetin have been protected from these changes as evidenced by the decreased
      myocardial levels of ER stress and fibrosis markers when compared with the
      vehicle-treated DCM rats. In addition, the myocardial dimensions and cardiac
      function were preserved significantly in the quercetin-treated rats in comparison
      with the DCM rats treated with vehicle alone. Interestingly, the rats treated
      with quercetin showed significant suppression of the myocardial endothelin-1 and
      also the mitogen activated protein kinases (MAPK) suggesting that the protection
      offered by quercetin treatment against progression of EAM involves the modulation
      of MAPK signalling cascade. Collectively, the present study provides data to
      support the role of quercetin in protecting the hearts of the rats with post
      myocarditis DCM.

PMID- 22145947
TI  - Complications of penile augmentation by use of nonmedical industrial silicone.
AB  - INTRODUCTION: Penile augmentation has been reported in the literature by
      injecting various materials by nonmedical persons. AIM: This study aims to
      present our experience in management of penile augmentation complications
      associated with injection or implantation of industrial silicone by lay persons.
      MAIN OUTCOME MEASURES: Early surgical intervention can lead to faster recovery
      and better cosmetic and functional outcome. METHODS: Two patients had injection
      of industrial silicone paste, and the other two had industrial silicone ring
      implantation. All the patients except one were presented after 13 months of the
      procedure. Patients with industrial silicone ring presented with multiple sinuses
      of penile skin in one, and abscess discharge pus from the site of implanted ring
      in the other. Both patients with injected silicone paste presented with swelling
      and deformity of the penis that interfered with their intercourse. Silicone ring
      patients underwent skin incision and drainage of the infected materials and
      extraction of the implants with delayed skin closure. The two patients with
      silicone paste injection underwent two-stage penile reconstructions using scrotal
      flap. RESULTS: Patients with extracted rings had smooth recovery with acceptable
      cosmetic outcome. One of them was not initially satisfied with the length of his
      penis that was overcome by short-term use of vacuum device. One of the patients
      with silicone paste injection had wound infection that was successfully treated
      with local wound care. Both had satisfactory penile length and acceptable
      cosmetic outcome. All patients had normal erectile function postoperatively.
      CONCLUSION: Complications of using industrial silicone injection can be drastic,
      and awareness of the public can avoid using of this material for penile
      augmentation.

PMID- 22145948
TI  - Intraventricular glioneuronal tumor with disseminated lesions at diagnosis--a
      case report.
AB  - A 55-year-old man presented with a large tumor in his lateral ventricles.
      Magnetic resonance imaging revealed disseminated lesions in the third and fourth
      ventricles at the time of diagnosis. The patient underwent a partial removal of
      the tumor in the lateral ventricles. Histologically, the surgical specimens
      showed glioneuronal differentiation with ganglion or ganglioid cells, Rosenthal
      fibers, oligodendroglia-like honeycomb appearances, a spongy pattern,
      perivascular pseudorosettes, and many hyalinized blood vessels. Papillary
      structure was not observed. The neuronal component showed a moderately high
      labeling index of Ki-67/MIB-1. We diagnosed this tumor as atypical
      intraventricular glioneuronal tumor. The disseminated lesions disappeared after
      chemoradiation therapy with temozolomide, and the residual tumors in the lateral
      ventricles remained stable for 3 years after the surgery. We discuss the
      pathological diagnosis, therapy and clinical course with review of the
      literatures.

PMID- 22145949
TI  - American dippers indicate contaminant biotransport by Pacific salmon.
AB  - Migrating salmon can increase productivity in Pacific Northwestern streams and
      lakes through the deposition of nutrients from their decomposing carcasses after
      spawning. Several studies also report simultaneous biotransport of persistent
      organic pollutants that have contaminated lake food webs, although no similar
      effect has been shown conclusively in rivers. We tested the prediction that
      salmon enhance contaminants in river food webs using the American dipper (Cinclus
      mexicanus), an aquatic songbird and a recognized indicator of stream quality.
      Over 3 years, we analyzed 29 dipper eggs and aquatic invertebrate samples from 14
      different rivers in 10 catchments in southern British Columbia, Canada to assess
      whether variations in autumn spawning density of Pacific salmon were reflected in
      dipper egg contamination or stable carbon and nitrogen isotopes. delta(13)C
      isotope signatures, but not delta(15)N, in aquatic invertebrates and dipper eggs
      increased among catchments in proportion to the average density of spawning
      salmon. Concentrations of brominated flame retardants (PBDEs),
      dichlorodiphenyltrichloroethane metabolites (DDTs), and chlordane compounds were
      related in part to the delta(13)C measure of salmon density, but mercury,
      chlorobenzenes, and polychlorinated biphenyls (PCBs) were explained better by
      dipper trophic level. We conclude that spawning Pacific salmon result in the
      increased availability of salmon fry as dipper prey and salmon are a significant
      source of PBDEs, DDTs, and chlordanes to river ecosystems. However, contrary to
      lake studies, postspawn concentrations of legacy PCBs in river birds, even in
      salmon-rich rivers, were not significantly higher than would be expected from
      atmospheric deposition alone. We recommend using delta(13)C isotopes to trace
      salmon-derived lipids which may persist over winter particularly in rivers, and
      are potentially a better reflection of lipophilic contaminant transfer.

PMID- 22145950
TI  - In vitro models for analysis of the hepatitis C virus life cycle.
AB  - Chronic hepatitis C virus (HCV) infection affects approximately 170 million
      people worldwide. HCV infection is a major global health problem as it can be
      complicated with liver cirrhosis and hepatocellular carcinoma. So far, there is
      no vaccine available and the non-specific, interferon (IFN)-based treatments now
      in use have significant side-effects and are frequently ineffective, as only
      approximately 50% of treated patients with genotypes 1 and 4 demonstrate HCV
      clearance. The lack of suitable in vitro and in vivo models for the analysis of
      HCV infection has hampered elucidation of the HCV life cycle and the development
      of both protective and therapeutic strategies against HCV infection. The present
      review focuses on the progress made towards the establishment of such models.

PMID- 22145951
TI  - beta-Puromycin selection of modified ribosomes for in vitro incorporation of beta
      amino acids.
AB  - Ribosomally mediated protein biosynthesis is limited to alpha-L-amino acids. A
      strong bias against beta-L-amino acids precludes their incorporation into
      proteins in vivo and also in vitro in the presence of misacylated beta-aminoacyl
      tRNAs. Nonetheless, earlier studies provide some evidence that analogues of
      aminoacyl-tRNAs bearing beta-amino acids can be accommodated in the ribosomal A
      site. Both functional and X-ray crystallographic data make it clear that the
      exclusion of beta-L-amino acids as participants in protein synthesis is a
      consequence of the architecture of the ribosomal peptidyltransferase center
      (PTC). To enable the reorganization of ribosomal PTC architecture through
      mutagenesis of 23S rRNA, a library of modified ribosomes having modifications in
      two regions of the 23S rRNA (2057-2063 and 2496-2507 or 2582-2588) was prepared.
      A dual selection procedure was used to obtain a set of modified ribosomes able to
      carry out protein synthesis in the presence beta-L-amino acids and to provide
      evidence for the utilization of such amino acids, in addition to alpha-L-amino
      acids. beta-Puromycin, a putative mimetic for beta-aminoacyl-tRNAs, was used to
      select modified ribosome variants having altered PTC architectures, thus
      potentially enabling incorporation of beta-L-amino acids. Eight types of modified
      ribosomes altered within the PTC have been selected by monitoring improved
      sensitivity to beta-puromycin in vivo. Two of the modified ribosomes, having
      2057AGCGUGA2063 and 2502UGGCAG2507 or 2502AGCCAG2507, were able to suppress UAG
      codons in E. coli dihydrofolate reductase (DHFR) and scorpion Opisthorcanthus
      madagascariensis peptide IsCT mRNAs in the presence of beta-alanyl-tRNA(CUA).

PMID- 22145952
TI  - Carbon monoxide, generated by heme oxygenase-1, mediates the enhanced
      permeability and retention effect in solid tumors.
AB  - The enhanced permeability and retention (EPR) effect is a unique
      pathophysiological phenomenon of solid tumors that sees biocompatible
      macromolecules (>40 kDa) accumulate selectively in the tumor. Various factors
      have been implicated in this effect. Herein, we report that heme oxygenase-1 (HO
      1; also known as heat shock protein 32) significantly increases vascular
      permeability and thus macromolecular drug accumulation in tumors. Intradermal
      injection of recombinant HO-1 in mice, followed by i.v. administration of a
      macromolecular Evans blue-albumin complex, resulted in dose-dependent
      extravasation of Evans blue-albumin at the HO-1 injection site. Almost no
      extravasation was detected when inactivated HO-1 or a carbon monoxide (CO)
      scavenger was injected instead. Because HO-1 generates CO, these data imply that
      CO plays a key role in vascular leakage. This is supported by results obtained
      after intratumoral administration of a CO-releasing agent
      (tricarbonyldichlororuthenium(II) dimer) in the same experimental setting,
      specifically dose-dependent increases in vascular permeability plus augmented
      tumor blood flow. In addition, induction of HO-1 in tumors by the water-soluble
      macromolecular HO-1 inducer pegylated hemin significantly increased tumor blood
      flow and Evans blue-albumin accumulation in tumors. These findings suggest that
      HO-1 and/or CO are important mediators of the EPR effect. Thus, anticancer
      chemotherapy using macromolecular drugs may be improved by combination with an HO
      1 inducer, such as pegylated hemin, via an enhanced EPR effect.

PMID- 22145953
TI  - Self-control training in children: a review of interventions for anxiety and
      depression and the role of parental involvement.
AB  - This review critically evaluates self-control skills interventions in the
      treatment of childhood anxiety and depression, outlining conditions under which
      these interventions are successful and the specific role of parents. Findings
      indicated that self-control skills interventions are successful with both
      children and adolescents, in the context of other cognitive behavioral techniques
      and as the primary treatment component, and with and without parental
      involvement. However, despite consistent evidence of success in both pre-post and
      waitlist control designs, self-control skills treatments have not demonstrated
      superior efficacy when compared to other active treatments. Continued application
      and evaluation of these interventions amongst children and adolescents are
      recommended.

PMID- 22145955
TI  - Differential expression of LeY and fucosyltransferase IV correlates with the
      receptivity of RL95-2 and HEC-1A human uterine epithelial cells.
AB  - Adhesion molecules expressed on the uterine endometrium are potential receptive
      markers in embryo implantation. RL95-2 and HEC-1A cell lines represent the high-
      and low-receptive endometrial epithelium respectively. LeY (Lewis Y) is a
      difucosylated oligosaccharide highly expressed in the endometrium of some species
      during implantation. alpha1, 3 fucosylation of LeY is catalysed by FUT4
      (fucosyltransferase IV), the key synthesis enzyme for LeY. We investigated
      whether the difference in receptivity between the 2 cell lines was related to
      different expressions of LeY and FUT4. RL95-2 cells expressed a higher level of
      LeY and FUT4 than HEC-1A cells, as shown by immunofluorescent staining, RT-PCR
      (reverse transcription-PCR) or Western blotting. FUT4-siRNA (small interfering
      RNA) transfection down-regulated FUT4 and LeY in RL95-2 cells, and inhibited the
      adhesion of the embryonic cells (JAR) to RL95-2 cell monolayer. FUT4-cDNA,
      however, increased the expression of FUT4 and LeY in HEC-1A cells, and increased
      the adhesion of embryonic cells to HEC-1A cell monolayer. Alterations of LeY
      level by up- or down-regulation of FUT4 also mediated EGFR (epidermal growth
      factor receptor)/MAPK (mitogen-activated protein kinase) signalling pathway. To
      conclude, the expression of LeY and FUT4 correlates with endometrial receptivity,
      making them potential new markers for the evaluation of endometrial receptivity.

PMID- 22145956
TI  - Systemic mastocytosis is uncommon in KIT D816V mutation positive core-binding
      factor acute myeloid leukemia.
AB  - The KIT D816V mutation is detected in the vast majority of adult cases of
      systemic mastocytosis (SM). The mutation is also frequently detected in core
      binding factor acute myeloid leukemia (CBF AML) defined by the presence of
      t(8;21)(q22;q22); RUNX1-RUNX1T1 or inv(16)(p13.1;q22)/t(16;16)(p13.1;q22); CBFB
      MYH11 chromosomal rearrangements, but whether the mutation is indicative of
      associated SM is unclear. In the present study, patients with CBF AML were
      therefore analyzed for the KIT D816V mutation and mutation positive cases
      subsequently analyzed for the presence of SM. The KIT D816V mutation was detected
      in eight of 20 cases of CBF AML, with the frequency in t(8;21)(q22;q22) and
      inv(16)(p13.1;q22) positive cases being 31% and 57%, respectively. The fraction
      of KIT D816V mutation positive cells was highly variable among the eight mutation
      positive patients, with levels ranging from 0.04 to 98% in a pretreatment blood
      sample. Five of the eight cases carried the mutation in a cell fraction below one
      tenth of the blast cell fraction, thus suggesting that KIT mutation is often a
      late event in leukemogenesis. None of the eight KIT D816V mutation positive cases
      fulfilled the World Health Organization diagnostic criteria of SM. The presence
      of the KIT D816V mutation in the CBF AML subgroup can therefore not be considered
      indicative of associated SM.

PMID- 22145957
TI  - Osteolytic bone lesions in non-transformed chronic lymphocytic leukemia are not
      as rare as suggested.

PMID- 22145958
TI  - MicroRNA-223 expression is uniformly down-regulated in B cell lymphoproliferative
      disorders and is associated with poor survival in patients with chronic
      lymphocytic leukemia.
AB  - MicroRNA-223 (miR-223) expression has been demonstrated to be stage-specific in B
      cell differentiation and associated with the outcome of chronic lymphocytic
      leukemia (CLL). However, the expression pattern of miR-223 in B cell
      lymphoproliferative disorders and its association with the outcome of Chinese
      patients with CLL have not been investigated. In this study, we demonstrated that
      miR-223 expression was significantly decreased in CLL, mantle cell lymphoma (MCL)
      and splenic marginal zone lymphoma (SMZL). In CLL, miR-223 expression decreased
      significantly with progression from early to advanced clinical stages and was
      significantly lower in patients with elevated beta(2)-microglobulin, unmutated
      immunoglobulin variable heavy chain (IgVH) gene or with disease progression or
      death. Using a cut-off determined by receiver operating characteristic (ROC)
      analysis optimizing concordance with IgVH mutational status, miR-223-negative and
      -positive groups were defined for 22 and 31 patients, respectively. The median
      progression-free survival (PFS) and overall survival of the miR-223-negative
      group were 13 and 40 months, respectively, significantly shorter than for the miR
      223-positive group (both not reached; p = 0.002 and p = 0.018, respectively).
      Multivariate analysis revealed that the absence of miR-223 was the only
      independent factor capable of predicting shorter PFS. In conclusion, miR-223 is
      uniformly down-regulated in B-LPDs and is a useful prognostic factor for patients
      with CLL.

PMID- 22145959
TI  - Infectious complications in adult acute myeloid leukemia: analysis of the Acute
      Leukemia French Association-9802 prospective multicenter clinical trial.
AB  - Infections are a major complication in patients with acute myeloid leukemia
      undergoing intensive chemotherapy. They remain a major cause of therapy
      associated morbidity and mortality, and represent a frequent cause of treatment
      withdrawal. An analysis of the medical charts of 459 younger adults included in
      the multicenter Acute Leukemia French Association (ALFA)-9802 trial showed that
      1369 febrile episodes occurred among the 459 registered patients, including fever
      without identifiable source (23%) and clinically or microbiologically documented
      infections (77%). Bloodstream infections occurred in 314 episodes, including 129
      documented episodes with Gram-positive and 96 with Gram-negative pathogens.
      Pulmonary infection was diagnosed in 144/1054 documented infectious episodes
      (14%). Invasive fungal infection was probable or proven in 116 patients. In all,
      15 patients died of infection-associated complications, of whom seven died during
      early induction therapy, one during salvage therapy and seven during
      consolidation therapy. Better supportive care strategies may improve overall
      survival in patients undergoing chemotherapy for acute myeloid leukemia.

PMID- 22145960
TI  - Diabetes and fracture healing: the skeletal effects of diabetic drugs.
AB  - INTRODUCTION: Over 39,000 diabetic patients are surgically treated for trauma and
      orthopaedic injuries annually in the UK, yet the effects of diabetic medications
      on the skeletal system is an under researched and under acknowledged field. AREAS
      COVERED: This review covers all English language novel experimental data reports
      investigating the effects of the main classes of diabetic drugs on the skeletal
      system, specifically their effects on fracture healing, located through the
      literature search engines Medline and Web of Science. EXPERT OPINION: Post
      surgical gylcaemic control is paramount in insulin-controlled type 1 diabetic
      patients. Data on pharmacological control compounds used in type 2 diabetes are
      limited. Reports to date indicate thiazolidinediones to exert anti-osteogenic
      effects, in contrast to the observed osteogenic effects of biguanides. Ongoing
      research is desirable to guide future clinical recommendations.

PMID- 22145961
TI  - Temperature dependence of ion transport in dilute tetrabutylammonium triflate
      acetate solutions and self-diffusion in pure acetate liquids.
AB  - Conductivities and static dielectric constants for 0.0055 M tetrabutylammonium
      trifluoromethanesulfonate in n-butyl acetate, n-pentyl acetate, n-hexyl acetate,
      n-octyl acetate, and n-decyl acetate have been collected over the temperature
      range of 0-80  degrees C. Self-diffusion coefficients and static dielectric
      constants of pure acetates were obtained over the same temperature range. Both
      temperature-dependent diffusion coefficients and ionic conductivities of these
      pure acetates and dilute acetate solutions can be accurately described by the
      compensated Arrhenius formalism. Activation energies were calculated from
      compensated Arrhenius plots for both conductivity and diffusion data. Activation
      energies are higher for conductivity data of 0.0055 M TbaTf-acetates compared to
      diffusion data of pure acetates. The plot of the exponential prefactor versus the
      dielectric constant yields a single master curve for both conductivity and
      diffusion data. These data support the argument that mass and charge transport
      are thermally activated processes in the acetates, as previously observed in
      alcohol-based electrolytes.

PMID- 22145962
TI  - Site-dependent actinic skin damage as risk factor for melanoma in a central
      European population.
AB  - Sun exposure is causal for melanoma but is subject to bias of recall so that it
      is difficult to dissect the role of particular patterns of sun exposure. In this
      hospital-based case-control study (n = 1991), we aimed to analyze pigmentation
      traits and signs of actinic damage at different anatomic locations as markers of
      melanoma risk in central European patients. Although all signs of actinic damage
      (freckling, wrinkling and solar lentigos) were significantly associated with
      melanoma risk in multivariate logistic regression models adjusting for age and
      sex, the strongest associations were observed for the dorsal parts of the body:
      adjusted odds ratios [OR] were 4.22 for wrinkling on the neck, 3.43 for solar
      lentigos and 3.37 for freckling on the back (all P < 0.001), respectively. These
      associations were independent of age, sex and pigmentation traits. Our results
      indicate that signs of actinic damage are predictors of melanoma risk,
      particularly on the back.

PMID- 22145964
TI  - Peri-orbital nodular fasciitis in a child.
AB  - Nodular fasciitis is an idiopathic, benign, nodular proliferation of connective
      tissue involving the superficial fascia. The clinical picture of a rapidly
      growing mass and the histopathological appearance of the lesion often give the
      false impression of a sarcoma. Commonly seen in the trunk and upper extremities
      of adults, the lesion is seen rarely in the orbital region. We report the first
      case of nodular fasciitis involving the periorbital region of a child from the
      Indian subcontinent.

PMID- 22145963
TI  - APOBEC3-mediated editing in HIV type 1 from pediatric patients and its
      association with APOBEC3G/CUL5 polymorphisms and Vif variability.
AB  - The APOBEC3 proteins are cytidine deaminases that can introduce G->A mutations in
      the HIV-1 plus DNA strand. This editing process may inhibit virus replication
      through lethal mutagenesis (hypermutation), but could also contribute to viral
      diversification leading to the emergence of escape forms. The HIV-1 Vif protein
      has the capacity to counteract APOBEC3 factors by recruiting a CUL5-based
      ubiquitin ligase complex that determines their proteasomal degradation. In this
      work, we analyzed the APOBEC3-mediated editing in proviral HIV-1 from perinatally
      infected children (n=93) in order to explore its association with polymorphisms
      of APOBEC3G and CUL5 genes (APOBEC3G H186R, APOBEC3G C40693T, and CUL5 SNP6), the
      Vif protein variability, and also the time to AIDS development. To calculate the
      level of editing, we have developed an index exploiting the properties of a
      region within the HIV-1 pol gene that includes the central polypurine tract
      (cPPT). We detected a reduced editing associated with the CUL5 SNP6 minor allele
      and also with certain Vif variants (mutations at sites 46, 122, and 160),
      although we found no evidence supporting an impact of APOBEC3 activity on disease
      progression. Thus, our findings suggest that APOBEC3-mediated editing of HIV-1
      could be modulated by host and virus genetic characteristics in the context of
      pediatric infection.

PMID- 22145965
TI  - The discriminative power of patient experience surveys.
AB  - BACKGROUND: Comparisons of patient experiences between providers are increasingly
      used as an index of performance. The present study describes the ability of
      patient experience surveys to discriminate between healthcare providers for
      various patient groups and quality aspects, and reports the sample sizes required
      for reliable (comparisons of) provider scores. METHOD: The consumer quality index
      is a family of surveys that are tailored to specific patient groups. Data was
      used from patients who underwent cataract surgery, patients who underwent hip or
      knee surgery, patients suffering from spinal disc herniation and patients
      suffering from varicose veins. Multi-level regression models were fitted to
      assess the proportion of variance in patient experiences that is attributable to
      providers for various quality aspects. RESULTS: The proportion of variance in
      patient experiences that is attributable to providers varied from 0.001 to 0.054.
      The required sample size for reliable estimates at the provider level varied from
      41 to 1967 per provider. Differences in discriminative power between patient
      groups and/or quality aspects were inconsistent, with one exception: for all
      groups, the discriminative power of experiences regarding change in physical
      functioning was particularly limited. CONCLUSIONS: From a statistical point of
      view, the discriminative power appears limited. The sample sizes required for
      reliable estimates are often substantial and deserve careful consideration when
      setting up measurements. Future research should evaluate the discriminative power
      by validating differences between providers in patient experiences with other
      indices and should explore other, more sensitive measures of patient experiences
      regarding treatment-related changes in physical functioning.

PMID- 22145966
TI  - A mechanistic study on the effect of ethanol and importance of water on
      permeation of drugs through human third-degree burn eschar.
AB  - Ethanol that affects hydration of skin and used in wound treatment formulations
      was studied here for its effect on permeation of drugs through burn eschar and to
      investigate the presence of a porous pathway in this barrier. In this study,
      permeations of clindamycin phosphate (CP, hydrophilic) and diazepam (lipophilic)
      through human burn eschar were investigated in the presence and absence of
      ethanol. Permeability coefficients (K(p) ) of CP and diazepam through hydrated
      eschar were calculated to be 13.1 * 10(-3)  and 17.4 * 10(-3)  cm/h respectively.
      These K(p)  values were decreased by about 1.5-5.3 and 2-10.7 times respectively
      upon the addition of 20-70% ethanol. Increased amount of ethanol decreased
      permeation flux of CP (2-20 times) and increased that of diazepam (3-80 times)
      from saturated solutions. Thermal analysis showed that ethanol dehydrates eschar
      and also changes its internal proteineous structure. Such changes were concluded
      to be the main reasons behind decreased K(p)  of both drugs. Comparison of K(p) 
      data suggests the possibility and importance of a pore pathway in permeation of
      both drugs through the hydrated burn eschar. Present results show that ethanol,
      and possibly other dehydrating agents, can decrease the permeability of eschar
      and that this effect should be considered in formulation developments.

PMID- 22145967
TI  - Diagnosis and medical treatment of lower urinary tract symptoms in adult men:
      applying specialist guidelines in clinical practice.
AB  - What's known on the subject? and What does the study add? Several sets of
      comprehensive treatment guidelines (national and international) exist for
      managing male lower urinary tract symptoms (LUTS), but these are not widely
      adopted in primary and secondary care, and are not consistently applied across
      Europe. This paper will improve the consistency of treatment approaches for adult
      males with LUTS by providing a clear, concise summary of existing treatment
      guidelines that can be easily adopted by urologists and primary care specialists.
      OBJECTIVE: To review current treatment guidelines (international and national) on
      managing male lower urinary tract symptoms (LUTS) and to summarize them for easy
      application in clinical practice. METHODS: A group of European urology
      specialists from primary and secondary care reviewed current treatment guidelines
      for male LUTS. RESULTS: The most appropriate recommendations for managing male
      LUTS were identified from existing international and national guidelines, and
      were summarized and simplified for use as a quick reference guide for healthcare
      professionals managing LUTS in adult males. CONCLUSIONS: Current guidelines for
      managing male LUTS were developed by urologists and are too complex for easy
      application in routine practice. This brief summary of current guidance should
      help to achieve consistent adoption of recommendations for best practice, improve
      working relationships between primary care specialists and urologists and clarify
      which patients' treatments should be managed entirely by urology specialists.

PMID- 22145968
TI  - Is hormonal therapy associated with better quality of life in transsexuals? A
      cross-sectional study.
AB  - INTRODUCTION: Although the impact of sex reassignment surgery on the self
      reported outcomes of transsexuals has been largely described, the data available
      regarding the impact of hormone therapy on the daily lives of these individuals
      are scarce. AIMS: The objectives of this study were to assess the relationship
      between hormonal therapy and the self-reported quality of life (QoL) in
      transsexuals while taking into account the key confounding factors and to compare
      the QoL levels between transsexuals who have, vs. those who have not, undergone
      cross-sex hormone therapy as well as between transsexuals and the general
      population (French age- and sex-matched controls). METHODS: This study
      incorporated a cross-sectional design that was conducted in three psychiatric
      departments of public university teaching hospitals in France. The inclusion
      criteria were as follows: 18 years or older, diagnosis of gender identity
      disorder (302.85) according to the Diagnostic and Statistical Manual, fourth
      edition text revision (DSM-IV TR), inclusion in a standardized sex reassignment
      procedure following the agreement of a multidisciplinary team, and pre-sex
      reassignment surgery. MAIN OUTCOME MEASURE: QoL was assessed using the Short Form
      36 (SF-36). RESULTS: The mean age of the total sample was 34.7 years, and the sex
      ratio was 1:1. Forty-four (72.1%) of the participants received hormonal therapy.
      Hormonal therapy and depression were independent predictive factors of the SF-36
      mental composite score. Hormonal therapy was significantly associated with a
      higher QoL, while depression was significantly associated with a lower QoL.
      Transsexuals' QoL, independently of hormonal status, did not differ from the
      French age- and sex-matched controls except for two subscales of the SF-36
      questionnaire: role physical (lower scores in transsexuals) and general health
      (lower scores in controls). CONCLUSION: The present study suggests a positive
      effect of hormone therapy on transsexuals' QoL after accounting for confounding
      factors. These results will be useful for healthcare providers of transgender
      persons but should be confirmed with larger samples using a prospective study
      design.

PMID- 22145969
TI  - Transcriptional regulation of MIR29B by PU.1 (SPI1) and MYC during neutrophil
      differentiation of acute promyelocytic leukaemia cells.

PMID- 22145970
TI  - Cage-catalyzed Knoevenagel condensation under neutral conditions in water.
AB  - A cationic coordination cage dramatically accelerates the Knoevenagel
      condensation of aromatic aldehydes in water under neutral conditions. The
      addition of a nucleophile to the aldehyde to generate anionic intermediates seems
      to be facilitated by the cationic environment of the cavity. The products are
      ejected from the cage as a result of the host-guest size discrepancy. As a
      result, the condensation is promoted by a catalytic amount of the cage.

PMID- 22145971
TI  - Patient expectations of podiatric surgery in the United Kingdom.
AB  - BACKGROUND: Patient expectations can be difficult to conceptualise and are liable
      to change with time, health and environmental factors. Patient expectation is
      known to influence satisfaction, however little is known about the expectations
      of patients attending for podiatric surgery. This paper will explore the
      expectations of a large cohort of patients undergoing elective foot surgery.
      METHODS: The UK based podiatric audit of surgery and clinical outcome measurement
      (PASCOM) audit system was applied to a consecutive cohort of patients undergoing
      elective podiatric surgery in Doncaster, South Yorkshire between 2004 and 2010.
      Data was collected relating to the surgical episode and patient expectations. A
      patient questionnaire was administered at 6 months post intervention. RESULTS: A
      total of 2910 unique surgical admissions were completed and satisfaction
      questionnaires were returned by 1869 patients. A total of 1430 patients answered
      question 1 which relates to patient expectations. Pain relief was the most
      frequent expectation with 1191 counts (52.3%), while footwear and mobility
      accounted for 16.6% and 16.4% respectively. Cosmesis counts occurred less
      commonly; 12.2%. 709 patients (49.6%) stated only a single expectation, 599
      patients (41.9%) stated two expectations, 114 patients (8%) stated three
      expectations and 7 patients (0.5%) stated 4 expectations. Pain relief was the
      dominant expectation accounting for 515 counts (72.6%) of patients who provided
      only one response. CONCLUSIONS: This paper demonstrates the expectations of a
      large cohort of podiatric surgery patients. For the most part patients expect
      pain relief, improved mobility and improved shoe fitting, while a small number of
      patients also expect a cosmetic improvement. Further research is required to
      determine the relationship between patient expectation and health related quality
      of life, and to determine whether podiatric surgery is successful in addressing
      the expectations of patients.

PMID- 22145972
TI  - The role of interagency collaboration in "joined-up" case management.
AB  - This article reports on research into the relationships that a group of case
      managers formed with local service providers in order to deliver integrated,
      "joined-up" services to young people experiencing homelessness and unemployment
      in the state of Victoria, Australia. Using a two-part customized survey tool, we
      explored the number and nature of relationships with other agencies. Two focus
      group discussions contributed to the interpretation of the survey findings. We
      found that these case managers maintained many relationships, mostly with housing
      and employment service providers. These relationships were predominantly
      cooperative in nature, and most could not easily be characterized as
      collaborative. Our research supports the view that, in an increasingly complex
      social service system, other forms of cooperation are usually appropriate for
      achieving the types of interorganizational relationships that are important to
      assist shared clients. Furthermore, this research supports the notion of a
      relationship continuum, finding that ratings of relationship elements were
      positively correlated with relationship type. This research indicates the
      importance of considering the pragmatic, contextual and situated practices that
      comprise interagency relationships, their fitness for purpose and the importance
      of cooperation for effective service provision.

PMID- 22145973
TI  - Arabidopsis thaliana TERMINAL FLOWER2 is involved in light-controlled signalling
      during seedling photomorphogenesis.
AB  - Plants respond to changes in the environment by altering their growth pattern.
      Light is one of the most important environmental cues and affects plants
      throughout the life cycle. It is perceived by photoreceptors such as phytochromes
      that absorb light of red and far-red wavelengths and control, for example,
      seedling de-etiolation, chlorophyll biosynthesis and shade avoidance response. We
      report that the terminal flower2 (tfl2) mutant, carrying a mutation in the
      Arabidopsis thaliana HETEROCHROMATIN PROTEIN1 homolog, functions in negative
      regulation of phytochrome dependent light signalling. tfl2 shows defects in both
      hypocotyl elongation and shade avoidance response. Double mutant analysis
      indicates that mutants of the red/far-red light absorbing phytochrome family of
      plant photoreceptors, phyA and phyB, are epistatic to tfl2 in far-red and red
      light, respectively. An overlap between genes regulated by light and by auxin has
      earlier been reported and, in tfl2 plants light-dependent auxin-regulated genes
      are misexpressed. Further, we show that TFL2 binds to IAA5 and IAA19 suggesting
      that TFL2 might be involved in regulation of phytochrome-mediated light responses
      through auxin action.

PMID- 22145974
TI  - Smoke decreases reversible oxidations S-glutathionylation and S-nitrosylation in
      mice.
AB  - Cigarette smoke causes irreversible oxidations in lungs, but its impact on
      reversible and physiologically relevant redox-dependent protein modifications
      remains to be investigated. Here the effect of cigarette smoke exposure in mice
      was investigated on the covalent binding of glutathione to protein thiols, known
      as S-glutathionylation (PSSG), which can be reversed by glutaredoxins (Grx).
      Also, protein S-nitrosylation (PSNO) which is the modification of protein thiols
      by NO and which is reversed by the enzyme alcohol dehydrogenase (ADH) 5 was
      examined. Both PSSG and PSNO levels in lung tissue were markedly decreased after
      4 weeks of cigarette smoke exposure. This coincided with attenuated protein free
      thiol levels and increased protein carbonylation. The expression of NOX4, DHE
      sensitive oxidant production and iNOS levels were induced by smoke, whereas Grx1
      mRNA expression and activity were attenuated. Free GSH levels, protein expression
      and activity of ADH5 were unaffected by smoke. Taken together, smoke exposure
      decreases reversible cysteine oxidations PSSG and PSNO and enhances protein
      carbonylation. These alterations are not associated with differences in some of
      the regulatory enzymes, but are likely the result of oxidative stress.

PMID- 22145975
TI  - Analysis of commercial and public bioactivity databases.
AB  - Activity data for small molecules are invaluable in chemoinformatics. Various
      bioactivity databases exist containing detailed information of target proteins
      and quantitative binding data for small molecules extracted from journals and
      patents. In the current work, we have merged several public and commercial
      bioactivity databases into one bioactivity metabase. The molecular presentation,
      target information, and activity data of the vendor databases were standardized.
      The main motivation of the work was to create a single relational database which
      allows fast and simple data retrieval by in-house scientists. Second, we wanted
      to know the amount of overlap between databases by commercial and public vendors
      to see whether the former contain data complementing the latter. Third, we
      quantified the degree of inconsistency between data sources by comparing data
      points derived from the same scientific article cited by more than one vendor. We
      found that each data source contains unique data which is due to different
      scientific articles cited by the vendors. When comparing data derived from the
      same article we found that inconsistencies between the vendors are common. In
      conclusion, using databases of different vendors is still useful since the data
      overlap is not complete. It should be noted that this can be partially explained
      by the inconsistencies and errors in the source data.

PMID- 22145976
TI  - HLA-B*08:01:08- joining the fold of silent alpha-1 proline mutations in HLA-B.
AB  - The sequence of HLA-B*08:01:08 differs from other HLA-B*08:01 alleles by at least
      two synonymous nucleotide exchanges.

PMID- 22145977
TI  - Thermal percolation in stable graphite suspensions.
AB  - Different from the electrical conductivity of conductive composites, the thermal
      conductivity usually does not have distinctive percolation characteristics. Here
      we report that graphite suspensions show distinct behavior in the thermal
      conductivity at the electrical percolation threshold, including a sharp kink at
      the percolation threshold, below which thermal conductivity increases rapidly
      while above which the rate of increase is smaller, contrary to the electrical
      percolation behavior. Based on microstructural and alternating current impedance
      spectroscopy studies, we interpret this behavior as a result of the change of
      interaction forces between graphite flakes when isolated clusters of graphite
      flakes form percolated structures. Our results shed light on the thermal
      conductivity enhancement mechanisms in nanofluids and have potential applications
      in energy systems.

PMID- 22145978
TI  - Conventional SLA and chemically modified SLA implants in patients with poorly
      controlled type 2 diabetes mellitus--a randomized controlled trial.
AB  - OBJECTIVE: The objective of this study was to evaluate the potential for a
      chemically modified Sand blasted, Large grit, Acid etched (SLA) surface, compared
      with a conventional SLA surface, to enhance implant healing and integration in
      poorly controlled diabetic patients, a group previously demonstrated to have
      compromises and delays in implant stabilization during the metabolically active
      healing period following implant placement. MATERIALS AND METHODS: The study
      enrolled 24 patients with type 2 diabetes, baseline HbA1c levels between 7.5
      11.4%, and a minimum of two posterior mandibular tooth sites at least 4 months
      following extraction and appropriate for implant placement. Each patient, at a
      randomly selected site, received an implant with the conventional SLA surface; at
      the second site, the patient received an implant with the chemically modified SLA
      (modSLA) surface. Thus, 48 study implants were placed. Implant stability was
      assessed using Resonance Frequency Analysis (RFA). Readings were taken from the
      buccal and proximal directions for each implant. Implant stability (ISQ) was
      assessed at the time of surgical placement (baseline) and 2, 3, 4, 6, 8, 10, 12,
      and 16 weeks following implant placement. RESULTS: No significant differences in
      implant stability were observed between conventional SLA implants and modSLA
      implants, and the time courses of implant stabilization following implant
      placement were similar for the two implant types. Baseline ISQ and minimum ISQ
      was slightly higher in subjects with higher HbA1c levels, but were similar during
      12-16 weeks following implant placement. Forty-seven (98%) of the 48 implants
      were determined to be successfully osseointegrated and continued to restoration.
      CONCLUSION: Implant stabilization was similar for the conventional SLA and
      chemically modified SLA implants in type 2 diabetic patients with relatively poor
      glycemic control. Furthermore, this study demonstrated clinically successful
      implant placement even in poorly controlled diabetic patients.

PMID- 22145979
TI  - STOP--in the name of mood: microtubule-associated proteins in mood and cognition.

PMID- 22145980
TI  - Methylation of mercury by bacteria exposed to dissolved, nanoparticulate, and
      microparticulate mercuric sulfides.
AB  - The production of the neurotoxic methylmercury in the environment is partly
      controlled by the bioavailability of inorganic divalent mercury (Hg(II)) to
      anaerobic bacteria that methylate Hg(II). In sediment porewater, Hg(II)
      associates with sulfides and natural organic matter to form chemical species that
      include organic-coated mercury sulfide nanoparticles as reaction intermediates of
      heterogeneous mineral precipitation. Here, we exposed two strains of sulfate
      reducing bacteria to three forms of inorganic mercury: dissolved Hg and sulfide,
      nanoparticulate HgS, and microparticulate HgS. The bacteria cultures exposed to
      HgS nanoparticles methylated mercury at a rate slower than cultures exposed to
      dissolved forms of mercury. However, net methylmercury production in cultures
      exposed to nanoparticles was 6 times greater than in cultures treated with
      microscale particles, even when normalized to specific surface area. Furthermore,
      the methylation potential of HgS nanoparticles decreased with storage time of the
      nanoparticles in their original stock solution. In bacteria cultures amended with
      nano-HgS from a 16 h-old nanoparticle stock, 6-10% of total mercury was converted
      to methylmercury after one day. In contrast, 2-4% was methylated in cultures
      amended with nano-HgS that was aged for 3 days or 1 week. The methylation of
      mercury derived from nanoparticles (in contrast to the larger particles) would
      not be predicted by equilibrium speciation of mercury in the aqueous phase (<0.2
      MUm) and was possibly caused by the disordered structure of nanoparticles that
      facilitated release of chemically labile mercury species immediately adjacent to
      cell surfaces. Our results add new dimensions to the mechanistic understanding of
      mercury methylation potential by demonstrating that bioavailability is related to
      the geochemical intermediates of rate-limited mercury sulfide precipitation
      reactions. These findings could help explain observations that the "aging" of
      mercury in sediments reduces its methylation potential and provide a basis for
      assessing and remediating methylmercury hotspots in the environment.

PMID- 22145981
TI  - Evaluation of fluorescence in situ hybridization to detect encapsulated Bacillus
      pumilus SAFR-032 spores released from poly(methylmethacrylate).
AB  - Bacillus pumilus SAFR-032 spores originally isolated from the Jet Propulsion
      Laboratory spacecraft assembly facility clean room are extremely resistant to UV
      radiation, H(2)O(2), desiccation, chemical disinfection and starvation compared
      to spores of other Bacillus species. The resistance of B. pumilus SAFR-032 spores
      to standard industrial clean room sterilization practices is not only a major
      concern for medical, pharmaceutical and food industries, but also a threat to the
      extraterrestrial environment during search for life via spacecraft. The objective
      of the present study was to investigate the potential of Alexa-FISH (fluorescence
      in situ hybridization with Alexa Fluor(r) 488 labeled oligonucleotide) method as
      a molecular diagnostic tool for enumeration of multiple sterilant-resistant B.
      pumilus SAFR-032 spores artificially encapsulated in, and released via organic
      solvent from, a model polymeric material: poly(methylmethacrylate) (Lucite,
      Plexiglas). Plexiglas is used extensively in various aerospace applications and
      in medical, pharmaceutical and food industries. Alexa-FISH signals were not
      detected from spores via standard methods for vegetative bacterial cells.
      Optimization of a spore permeabilization protocol capitalizing on the synergistic
      action of proteinase-K, lysozyme, mutanolysin and Triton X-100 facilitated
      efficient spore detection by Alexa-FISH microscopy. Neither of the Alexa-probes
      tested gave rise to considerable levels of Lucite- or solvent-associated
      background autofluorescence, demonstrating the immense potential of Alexa-FISH
      for rapid quantification of encapsulated B. pumilus SAFR-032 spores released from
      poly(methylmethacrylate).

PMID- 22145982
TI  - Epithelioid hemangioendothelioma of the forearm with radius involvement. Case
      report.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare, well-differentiated endothelial
      tumor with intermediate malignancy which develops more frequently from the
      peripheral veins, generally in the lower limb. Bone EHE comprises less than 1% of
      the bone neoplasms. We present the case of a young man, 24-year-old, with EHE of
      the forearm with secondary involvement of the distal radius. The location and the
      extension of the tumor allowed a wide excision, without the reconstruction of
      radius, followed by adjuvant radiotherapy, with a subsequent favorable evolution.
      Based on the clinical, radiographic, and pathological features of the EHE review,
      we concluded that it is difficult to adopt a standardized therapeutic approach
      due to the extremely low incidence of the bone involvement in EHE and the
      variable tendencies towards malignancy of this tumor. To our knowledge this is
      the third case of EHE with the involvement of the radius.

PMID- 22145983
TI  - Opportunistic and continuing health care for injecting drug users from a nurse
      run needle syringe program-based primary health-care clinic.

PMID- 22145984
TI  - A Phase I, dose-finding and pharmacokinetic study of olaparib (AZD2281) in
      Japanese patients with advanced solid tumors.
AB  - Olaparib (AZD2281) is an orally active Poly(ADP-ribose) polymerase (PARP)
      inhibitor with favorable antitumor activity in advanced ovarian and breast
      cancers with BRCA1/2 mutations in Western (USA and European) studies. This Phase
      I dose-finding study evaluated the tolerability, pharmacokinetics, PARP
      inhibitory activity, and antitumor activity of olaparib in Japanese patients with
      solid tumors. Olaparib was administered as a single-dose on day 1, followed by
      twice-daily dosing for 28 days from 48 h after a single dose. Doses were
      escalated from 100 mg b.i.d. in successive cohorts, up to a maximum of 400 mg
      b.i.d. The present study enrolled 12 patients (n = 3, 3, and 6 in 100, 200 and
      400-mg b.i.d. levels, respectively). The most common adverse events were nausea,
      increased blood creatinine, decreased hematocrit, leukopenia and lymphopenia;
      dose-limiting toxicities were not observed up to and including the 400-mg b.i.d.
      dose level. Following twice-daily dosing, olaparib showed no marked increase in
      exposure at steady state over that expected from the single-dose
      pharmacokinetics. PARP-1 inhibition was observed from the 100-mg b.i.d. dose
      level in peripheral blood mononuclear cells from 6 h post-dose on day 1 during
      the multiple-dosing period. A patient with metastatic breast cancer (100 mg
      b.i.d.) had a partial response for 13 months and four patients (two each in the
      200 and 400-mg b.i.d. levels) had stable disease >8 weeks. Olaparib was well
      tolerated up to the 400-mg b.i.d. dose in Japanese patients with solid tumors.
      Preliminary evidence of antitumor activity was observed.

PMID- 22145985
TI  - Treatment with endotracheal therapeutics after sarin microinstillation inhalation
      exposure increases blood cholinesterase levels in guinea pigs.
AB  - Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were
      measured in the blood and tissues of animals that are treated with a number of
      endotracheally aerosolized therapeutics for protection against inhalation
      toxicity to sarin. Therapeutics included, aerosolized atropine methyl bromide
      (AMB), scopolamine or combination of AMB with salbutamol, sphingosine 1
      phosphate, keratinocyte growth factor, adenosine A1 receptor antisense
      oligonucleotide (EPI2010), 2,3-diacetyloxybenzoic acid (2,3 DABA), oxycyte, and
      survanta. Guinea pigs exposed to 677.4 mg/m(3) or 846.5 mg/m(3) (1.2 LCt(50))
      sarin for 4 min using a microinstillation inhalation exposure technique and
      treated 1 min later with the aerosolized therapeutics. Treatment with all
      therapeutics significantly increased the survival rate with no convulsions
      throughout the 24 h study period. Blood AChE activity determined using
      acetylthiocholine as substrate showed 20% activity remaining in sarin-exposed
      animals compare to controls. In aerosolized AMB and scopolamine-treated animals
      the remaining AChE activity was significantly higher (45-60%) compared to sarin
      exposed animals (p < 0.05). Similarly, treatment with all the combination
      therapeutics resulted in significant increase in blood AChE activity in
      comparison to sarin-exposed animals although the increases varied between
      treatments (p < 0.05). BChE activity was increased after treatment with
      aerosolized therapeutics but was lesser in magnitude compared to AChE activity
      changes. Various tissues showed elevated AChE activity after therapeutic
      treatment of sarin-exposed animals. Increased AChE and BChE activities in animals
      treated with nasal therapeutics suggest that enhanced breathing and reduced
      respiratory toxicity/lung injury possibly contribute to rapid normalization of
      chemical warfare nerve agent inhibited cholinesterases.

PMID- 22145987
TI  - Effects of concentration and temperature on the dynamic behavior of PAA-g-PEO
      aqueous solutions with different counterion species: a dielectric spectroscopy
      study.
AB  - Dielectric properties of PAA-g-PEO-7% solutions with different counterions were
      measured as a function of concentration and temperature over a frequency range of
      40 Hz to 110 MHz. After the contribution of electrode polarization effects was
      subtracted, the dielectric spectra of PAA-g-PEO-7% solutions showed three
      relaxation processes in the experimental frequency range, named low-, mid-, and
      high-frequency relaxation. The observed three relaxations were strictly analyzed
      by using the Cole-Cole relaxation function, and the dielectric parameters
      (dielectric increment Deltaepsilon and the relaxation time tau) were obtained.
      The scaling relation of dielectric increment and relaxation time of high
      frequency with concentration C(p) were obtained and compared with the predictions
      of scaling theories. The information on the dynamics and microstructure of PAA-g
      PEO-7% was obtained. Using different counterion species, the mid- and high
      frequency relaxation mechanisms were attributed to the fluctuation of condensed
      counterions and free counterions, respectively, and the low-frequency relaxation
      was considered to be caused by the interface polarization of a complex formed by
      the hydrogen bonding between carboxylic group of PAA and ether oxygen on the side
      chain PEO. In addition, by means of Eyring equation, the thermodynamic
      parameters, enthalpy change DeltaH and entropy change DeltaS, of the three
      relaxations were calculated from the relaxation time and discussed from the
      microscopic thermodynamical view.

PMID- 22145986
TI  - Second-contact shell mutation diminishes streptavidin-biotin binding affinity
      through transmitted effects on equilibrium dynamics.
AB  - We report a point mutation in the second contact shell of the high-affinity
      streptavidin-biotin complex that appears to reduce binding affinity through
      transmitted effects on equilibrium dynamics. The Y54F streptavidin mutation
      causes a 75-fold loss of binding affinity with 73-fold faster dissociation, a
      large loss of binding enthalpy (DeltaDeltaH = 3.4 kcal/mol at 37  degrees C), and
      a small gain in binding entropy (TDeltaDeltaS = 0.7 kcal/mol). The removed Y54
      hydroxyl is replaced by a water molecule in the bound structure, but there are no
      observable changes in structure in the first contact shell and no additional
      changes surrounding the mutation. Molecular dynamics simulations reveal a large
      increase in the atomic fluctuation amplitudes for W79, a key biotin contact
      residue, compared to the fluctuation amplitudes in the wild-type. The increased
      W79 atomic fluctuation amplitudes are caused by loss of water-mediated hydrogen
      bonds between the Y54 hydroxyl group and peptide backbone atoms in and near W79.
      We propose that the increased atomic fluctuation amplitudes diminish the
      integrity of the W79-biotin interaction and represents a loosening of the
      "tryptophan collar" that is critical to the slow dissociation and high affinity
      of streptavidin-biotin binding. These results illustrate how changes in protein
      dynamics distal to the ligand binding pocket can have a profound impact on ligand
      binding, even when equilibrium structure is unperturbed.

PMID- 22145988
TI  - Comparison of cosmetic outcome between single-incision laparoscopic
      cholecystectomy and conventional laparoscopic cholecystectomy: an objective
      study.
AB  - BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) has been
      projected to have better cosmetic outcome compared with conventional laparoscopic
      cholecystectomy (CLC). However, there are scarce data that have objectively
      compared the patient's perception of cosmetic outcome after SILSC and CLC.
      METHODS: The SILC and CLC patients, who were operated in the last 2 years, were
      personally interviewed and assessed using the Patient Scar Assessment
      Questionnaire. A lower score indicated a better patient outcome. The satisfaction
      with the appearance and the symptoms due to the scars was assessed in all the
      patients. RESULTS: Fifty-two patients were included in the study (25 SILC, 27
      CLC). The age and sex distributions and body mass indexes were similar in both
      groups. The scores of different parameters assessed as per Patient Scar
      Assessment Questionnaire-appearance (SILC, 1.08 +/- 0.4; CLC, 1.14 +/- 0.5:
      P=.57), symptoms (SILC, 1.16 +/- 0.5; CLC, 1.18 +/- 0.4; P=.83), scar
      consciousness (SILC, 1.04 +/- 0.2; CLC, 1.07 +/- 0.3; P=.6), satisfaction with
      symptoms (SILC, 1.12 +/- 0.3; CLC, 1.18 +/- 0.4; P=.52), and satisfaction with
      appearance (SILC, 1.04 +/- 0.2; CLC, 1.11 +/- 0.3; P=.34)-were similar in both
      groups. The overall satisfaction scores were also statistically similar in both
      groups (SILC, 5.44 +/- 1.4; CLC, 5.70 +/- 1.7; P=.54). Overall, a majority of
      patients (>80%) in both groups gave the lowest score (1), indicating maximum
      satisfaction, in all the categories. CONCLUSIONS: Patient perception regarding
      cosmetic outcome after SILC and CLC was similar in both groups. SILC does not
      seem to offer any significant cosmetic advantage over CLC. This point needs to be
      assessed in detail by larger studies, as cosmetic benefit is projected as one of
      the major advantages of single-incision surgery.

PMID- 22145990
TI  - Adaptation of ammonia-oxidizing microorganisms to environment shift of paddy
      field soil.
AB  - Adaptation of microorganisms to the environment is a central theme in microbial
      ecology. The objective of this study was to investigate the response of ammonia
      oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) to a soil medium
      shift. We employed two rice field soils collected from Beijing and Hangzhou,
      China. These soils contained distinct AOB communities dominated by Nitrosomonas
      in Beijing rice soil and Nitrosospira in Hangzhou rice soil. Three mixtures were
      generated by mixing equal quantities of Beijing soil and Hangzhou soil (BH),
      Beijing soil with sterilized Hangzhou soil (BSH), and Hangzhou soil with
      sterilized Beijing soil (HSB). Pure and mixed soils were permanently flooded, and
      the surface-layer soil where ammonia oxidation occurred was collected to
      determine the response of AOB and AOA to the soil medium shift. AOB populations
      increased during the incubation, and the rates were initially faster in Beijing
      soil than in Hangzhou soil. Nitrosospira (cluster 3a) and Nitrosomonas (communis
      cluster) increased with time in correspondence with ammonia oxidation in the
      Hangzhou and Beijing soils, respectively. The 'BH' mixture exhibited a shift from
      Nitrosomonas at day 0 to Nitrosospira at days 21 and 60 when ammonia oxidation
      became most active. In 'HSB' and 'BSH' mixtures, Nitrosospira showed greater
      stimulation than Nitrosomonas, both with and without N amendment. These results
      suggest that Nitrosospira spp. were better adapted to soil environment shifts
      than Nitrosomonas. Analysis of the AOA community revealed that the composition of
      AOA community was not responsive to the soil environment shifts or to nitrogen
      amendment.

PMID- 22145991
TI  - Elevated expression of Rad18 regulates melanoma cell proliferation.
AB  - The E3 ligase Rad18 is a key regulator for the lesion bypass pathway, which plays
      an important role in genomic stability. However, the status of Rad18 expression
      in melanoma is not known. Using melanoma tissue microarray (TMA), we showed that
      nuclear Rad18 expression was upregulated in primary and metastatic melanoma
      compared to dysplastic nevi. Rad18 expression was significantly reduced in sun
      exposed sites compared to the sun-protected sites. Strong Rad18 expression
      correlated with worse 5-year patient survival and was an independent prognostic
      factor for melanoma found in the sun-protected sites. Furthermore, we showed that
      melanoma cell proliferation and the expression of pAkt and cyclin D1 were reduced
      upon Rad18 knockdown. We, for the first time, showed that Rad18 is significantly
      increased in melanoma and predicts the poor outcome for melanoma in the sun
      protected sites. Rad18 is involved in the regulation of melanoma cell
      proliferation, which can be exploited in designing new strategy for melanoma
      treatment.

PMID- 22145992
TI  - Prevalence and predictors of sexual problems in men aged 75-95 years: a
      population-based study.
AB  - INTRODUCTION: Hypogonadism is associated with impaired libido and erectile
      dysfunction in young men, but the causes of sexual dysfunction in older men are
      less well understood. AIM: To determine the prevalence and predictors of sexual
      problems in older men. MAIN OUTCOME MEASURE: Sexual problems, as assessed by a
      self-reported questionnaire. METHODS: This was a population-based, cohort study
      of 3,274 community-dwelling men aged 75-95 years (mean 82 years) from Perth,
      Western Australia. Questionnaires in 2001-2004 and 2008-2009 assessed social and
      medical risk factors. Sex hormones were measured in 2001-2004. Predictors of
      sexual problems, measured in 2008-2009, were assessed cross-sectionally in the
      entire sample, and longitudinally in a subset of 1,744 men with sex hormone data.
      RESULTS: Sexual problems were highly prevalent, with 49.4% (95% confidence
      interval 47.7% to 51.1%) reporting erectile problems, 47.7% (45.9% to 49.4%)
      lacking interest in sexual activity, 38.7% (37.0% to 40.3%) unable to climax, and
      20.4% (19.1% to 21.8%) anxious about their ability to perform sexually. Painful
      and unpleasurable sex were less common (<5%). Overall, 72.0% (70.5% to 73.6%)
      reported at least one problem. In multivariate binary logistic regression
      analyses, cardiovascular disease, diabetes, depression, prostate disorders, and
      insomnia were the factors most commonly associated with sexual problems. Low
      testosterone levels were associated with lack of interest in sex, but not with
      other complaints. CONCLUSIONS: Sexual problems are common in elderly men. Chronic
      disease, depression, and insomnia appear to be the main modifiable risk factors.
      Androgen deficiency is unlikely to be a major cause of sexual problems in this
      age group.

PMID- 22145993
TI  - A thermostable GH45 endoglucanase from yeast: impact of its atypical
      multimodularity on activity.
AB  - BACKGROUND: The gene encoding an atypical multi-modular glycoside hydrolase
      family 45 endoglucanase bearing five different family 1 carbohydrate binding
      modules (CBM1), designated PpCel45A, was identified in the Pichia pastoris GS115
      genome. RESULTS: PpCel45A (full-length open reading frame), and three derived
      constructs comprising (i) the catalytic module with its proximal CBM1, (ii) the
      catalytic module only, and (iii) the five CBM1 modules without catalytic module,
      were successfully expressed to high yields (up to 2 grams per litre of culture)
      in P. pastoris X33. Although the constructs containing the catalytic module
      displayed similar activities towards a range of glucans, comparison of their
      biochemical characteristics revealed striking differences. We observed a high
      thermostability of PpCel45A (Half life time of 6 h at 80 degrees C), which
      decreased with the removal of CBMs and glycosylated linkers. However, both
      binding to crystalline cellulose and hydrolysis of crystalline cellulose and
      cellohexaose were substantially boosted by the presence of one CBM rather than
      five. CONCLUSIONS: The present study has revealed the specific features of the
      first characterized endo beta-1,4 glucanase from yeast, whose thermostability is
      promising for biotechnological applications related to the saccharification of
      lignocellulosic biomass such as consolidated bioprocessing.

PMID- 22145994
TI  - Characterization of protease resistance-associated mutations in HIV type 1 drug
      naive patients following the increasing prevalence of the CRF02_AG strain in
      Morocco.
AB  - The purpose of this study was to investigate the amino acid substitutions in the
      protease of HIV-1 B and non-B subtypes and evaluate whether the emergence of
      resistance-associated mutations (RAMs) could have a significant correlation with
      the increasing prevalence of CRF02_AG strains in Morocco. A total of 162 protease
      gene sequences were successfully amplified from drug-naive HIV-1-infected
      individuals. We identified eight (sub)subtypes and CRFs: B(66%), A1(3.7%),
      C(1.2%), F1(0.6%), F2(0.6%), G(1.2%), CRF02_AG(25.3%), and CRF01_AE(1.2%).
      Phylogenetic analysis of CRF02_AG strains showed that 9.8% of isolates had a
      closer connection with reference strains from Morocco and 15.4% clustered with
      reference strains from eight West African and three European countries. When
      compared to the B subtype, patients with the CRF02_AG strain had a significantly
      higher prevalence of mutations associated with resistance to some antiprotease
      drugs, mainly tipranavir (TPV): H69K (97% vs. 5%; p<0.0001), L89M (95% vs. 1%;
      p<0.0001), and M36I/L (93% vs. 44%; p<0.0001). Most of the CRF02_AG strains (97%)
      significantly showed at least two TPV-RAMs (p=0.002) compared to the B subtype
      (7%). Multivariate analysis revealed that CRF02_AG infection was the only factor
      highly associated with the occurrence of more than two TPV-RAMs (C=0.42;
      p<0.0001). These results support the importance of transmitted drug resistance
      mutations (M36I/L, H69K, and L89M) in the protease gene of HIV-1 CRF02_AG
      isolates. This HIV drug resistance transmission before protease inhibitor (PI)
      exposure raises concern about its influence on the susceptibility of CRF02_AG
      strains to some PIs, especially tipranavir, which will soon be introduced as part
      of the second line therapeutic regimens in Morocco.

PMID- 22145995
TI  - Blood loss during radical prostatectomy: impact on clinical, oncological and
      functional outcomes and complication rates.
AB  - Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject?
      and What does the study add? It is generally accepted in the medical community
      that total and intra-operative blood loss after RALP is significantly lower in
      comparison with ORRP. This has led to speculation that less bleeding results in
      better visualization of the operative field resulting in superior potency and
      continence. Blood loss (BL) during ORRP does not adversely impact clinical and
      functional outcomes irrespective of how BL is defined. Thus, the lower BL
      associated with RALP would not be expected to improve functional or oncological
      outcomes. OBJECTIVE: To determine the short- and long-term impact of blood loss
      (BL) on clinical, oncological and functional outcomes as well as complication
      rates after an open radical retropubic prostatectomy (ORRP). PATIENTS AND
      METHODS: Between 2000 and 2008, 1567 men who underwent an ORRP participated in
      our prospective longitudinal outcomes study. Haematocrit (Hct) levels,
      transfusion rates, BL and complications were recorded prospectively. Validated,
      self-administered quality-of-life (QoL) questionnaires were completed at
      baseline, 3, 6 and 12 months and yearly thereafter. Urinary function and erectile
      dysfunction were assessed using AUA Symptom Score and the UCLA Prostate Cancer
      Index and analysis of variance (anova)/chi-square tests were used to compare
      clinical, BL, biochemical recurrence (BCR) and QoL outcomes amongst the three
      groups for continuous/categorical variables. RESULTS: The mean estimated BL was
      742.7 (45 to 3500) mL and 5.4% and 3.8% received an autologous (AU) or allogeneic
      (AL) blood transfusions, respectively. The average baseline, induction,
      postoperative and discharge Hct was 43.8%, 48.3%, 35.7% and 34.1%, respectively.
      The estimated BL and the rate of change of Hct correlated moderately (r=0.41,
      P<0.0001). Tertiles of BL were based on the difference between induction and
      discharge Hct (Delta 1) and the average Delta 1 for Groups 1, 2 and 3 were 7.9%,
      12.7% and 17.2%, respectively. Intra-operative, early/delayed complications,
      length of hospital stay (LoS), SM surgical margins status, anastomotic stricture
      and BCR were not statistically different (P<0.001) and the mean AUASS, UCLA
      Prostate Cancer urinary bother scores, urinary function scores, sexual
      bother/function scores at 24 months were similar amongst all tertiles (P>0.05).
      CONCLUSIONS: BL during ORRP does not adversely impact clinical and functional
      outcomes irrespective of how BL is defined. Thus, the lower BL associated with
      robotic-assisted laparoscopic prostatectomy (RALP) in and of itself would not be
      expected to improve functional or oncological outcomes.

PMID- 22145996
TI  - Reaction mechanism in crystalline solids: kinetics and conformational dynamics of
      the Norrish type II biradicals from alpha-adamantyl-p-methoxyacetophenone.
AB  - In an effort to determine the details of the solid-state reaction mechanism and
      diastereoselectivity in the Norrish type II and Yang cyclization of crystalline
      alpha-adamantyl-p-methoxyacetophenone, we determined its solid-state quantum
      yields and transient kinetics using nanocrystalline suspensions. The transient
      spectroscopy measurements were complemented with solid-state NMR spectroscopy
      spin-lattice relaxation experiments using isotopically labeled samples and with
      the analysis of variable-temperature anisotropic displacement parameters from
      single-crystal X-ray diffraction to determine the rate of interconversion of
      biradical conformers by rotation of the globular adamantyl group. Our
      experimental findings include a solid-state quantum yield for reaction that is 3
      times greater than that in solution, a Norrish type II hydrogen-transfer reaction
      that is about 8 times faster in crystals than in solution, and a biradical decay
      that occurs on the same time scale as conformational exchange, which helps to
      explain the diastereoselectivity observed in the solid state.

PMID- 22145997
TI  - Lack of unwanted effects of oseltamivir carboxylate in juvenile rats after
      subcutaneous administration.

PMID- 22145998
TI  - Relapsing insulin-induced lipoatrophy, cured by prolonged low-dose oral
      prednisone: a case report.
AB  - INTRODUCTION: Circumscript, progressing lipoatrophy at the insulin injection
      sites is an unexplained, however rare condition in diabetes mellitus. CASE
      PRESENTATION: We report a case of severe localised lipoatrophy developing during
      insulin pump-treatment (continuous subcutaneous insulin infusion) with the
      insulin analogue lispro (Humalog(r)) in a woman with type-1 diabetes mellitus.
      After 11 months of progressing lipoatrophy at two spots on the abdomen, low-dose
      prednisone (5-10 mg) p.o. was given at breakfast for 8 months, whereby the
      atrophic lesions centripetally re-filled with subcutaneous fat tissue (confirmed
      by MRI) despite ongoing use of insulin lispro. However, 4 weeks after cessation
      of prednisone, lipoatrophy relapsed, but resolved after another 2 months of low
      dose prednisone. No further relapse was noted during 12 months of follow-up on
      insulin-pump therapy with Humalog(r). CONCLUSION: Consistent with an assumed
      inflammatory nature of the condition, low-dose oral prednisone appeared to have
      cured the lipoatrophic reaction in our patient. Our observation suggests a
      temporary intolerance of the subcutaneous fat tissue to insulin lispro
      (Humalog(r)), triggered by an unknown endogenous mechanism.

PMID- 22145999
TI  - Frequency of nurse-physician collaborative behaviors in an acute care hospital.
AB  - A new culture bolstering collaborative behavior among nurses and physicians is
      needed to merge the unique strengths of both professions into opportunities to
      improve patient outcomes. To meet this challenge it is fundamental to comprehend
      the current uses of collaborative behaviors among nurses and physicians. The
      purpose of this descriptive study was to delineate frequently used from
      infrequently used collaborative behaviors of nurses and physicians in order to
      generate data to support specific interventions for improving collaborative
      behavior. The setting was an acute care hospital, and participants included 114
      registered nurses and 33 physicians with active privileges. The Nurse-Physician
      Collaboration Scale was used to measure the frequency of use of nurse-physician
      collaborative behaviors self-reported by nurses and physicians. The background
      variables of gender, age, education, ethnicity, years of experience, years
      practiced at the current acute care hospital, practice setting and professional
      certification were accessed. In addition to analyzing the frequency of
      collaborative behaviors, this study compares levels of collaborative behavior
      reported by nurses and physicians.

PMID- 22146000
TI  - Stand structure modulates the long-term vulnerability of Pinus halepensis to
      climatic drought in a semiarid Mediterranean ecosystem.
AB  - We investigated whether stand structure modulates the long-term physiological
      performance and growth of Pinus halepensis Mill. in a semiarid Mediterranean
      ecosystem. Tree radial growth and carbon and oxygen stable isotope composition of
      latewood (delta(13)C(LW) and delta(18)O(LW), respectively) from 1967 to 2007 were
      measured in P. halepensis trees from two sharply contrasting stand types: open
      woodlands with widely scattered trees versus dense afforested stands. In both
      stand types, tree radial growth, delta(13)C(LW) and delta(18)O(LW) were strongly
      correlated with annual rainfall, thus indicating that tree performance in this
      semiarid environment is largely determined by inter-annual changes in water
      availability. However, trees in dense afforested stands showed consistently
      higher delta(18)O(LW) and similar delta(13)C(LW) values compared with those in
      neighbouring open woodlands, indicating lower stomatal conductance and
      photosynthesis rates in the former, but little difference in water use efficiency
      between stand types. Trees in dense afforested stands were more water stressed
      and showed lower radial growth, overall suggesting greater vulnerability to
      drought and climate aridification compared with trees in open woodlands. In this
      semiarid ecosystem, the negative impacts of intense inter-tree competition for
      water on P. halepensis performance clearly outweigh potential benefits derived
      from enhanced infiltration and reduced run-off losses in dense afforested stands.

PMID- 22146001
TI  - The deletion of STOP/MAP6 protein in mice triggers highly altered mood and
      impaired cognitive performances.
AB  - The microtubule-associated Stable Tubulie Only Polypeptide (STOP; also known as
      MAP6) protein plays a key role in neuron architecture and synaptic plasticity,
      the dysfunctions of which are thought to be implicated in the pathophysiology of
      psychiatric diseases. The deletion of STOP in mice leads to severe disorders
      reminiscent of several schizophrenia-like symptoms, which are also associated
      with differential alterations of the serotonergic tone in somas versus terminals.
      In STOP knockout (KO) compared with wild-type mice, serotonin (5-HT) markers are
      found to be markedly accumulated in the raphe nuclei and, in contrast, deeply
      depleted in all serotonergic projection areas. In the present study, we carefully
      examined whether the 5-HT imbalance would lead to behavioral consequences
      evocative of mood and/or cognitive disorders. We showed that STOP KO mice
      exhibited depression-like behavior, associated with a decreased anxiety-status in
      validated paradigms. In addition, although STOP KO mice had a preserved very
      short-term memory, they failed to perform well in all other learning and memory
      tasks. We also showed that STOP KO mice exhibited regional imbalance of the
      norepinephrine tone as observed for 5-HT. As a consequence, mutant mice were
      hypersensitive to acute antidepressants with different selectivity. Altogether,
      these data indicate that the deletion of STOP protein in mice caused deep
      alterations in mood and cognitive performances and that STOP protein might have a
      crucial role in the 5-HT and norepinephrine networks development.

PMID- 22146002
TI  - Effectiveness of different interdental brushes on cleaning the interproximal
      surfaces of teeth and implants: a randomized controlled, double-blind cross-over
      study.
AB  - OBJECTIVES: To compare the interproximal cleansing efficacy of the novel, waist
      shaped Circum brush (Topcaredent, Switzerland; CB) with that of a straight soft
      interdental brush (IB) (TePe, Sweden; SB) on posterior surfaces. MATERIAL &
      METHODS: Eight patients after completion of initial periodontal therapy abolished
      oral hygiene for 3 days. Baseline plaque scores (PlI, Silness & Loe ) were
      assessed on eight surfaces of all premolars and molars. Subsequently, an
      instructed nurse applied at random one of the two IB, three times per interdental
      space . Following this, registration of the PlI was repeated by the same blinded
      examiner. After a 2-week recovery, patients abolished oral hygiene practices for
      another 3 days. Again, pre-and post-brushing PlI were recorded by the same
      examiner. The second IB was now applied. RESULTS: Patient mean PlI and site PlI
      were evaluated before and after application of the SB or CB respectively. Paired
      t-tests were performed to yield statistically significant differences. The
      reduction of biofilm from before to after the use of the IB on a subject basis
      was highly significant (P < 0.0001). The mean PlI after the use of the CB was
      significantly lower than after the use of the SB (P < 0.0001). Comparing the PlI
      of the line angles (MB, ML, DB, DL), significantly more biofilm had been removed
      by applying CB compared with SB (P < 0.0001). Moreover, comparing the PlI of the
      buccal (MB, DB) or the lingual line angles (DL, ML) yielded a significantly
      higher reduction of biofilm in favour of the CB (P < 0.0001). The reduction of
      the PlI in the mid-interproximal portion, both mesially and distally did not
      differ significantly between CB and ST. No biofilm reduction was seen on the
      buccal sites with either IB. CONCLUSION: The application of the waist-shaped
      Circum IB resulted in significantly lower PlI scores than the use of a straight
      IB. This was predominantly due to the higher cleansing effect of the waist-shaped
      CB on the buccal and lingual line angles.

PMID- 22146003
TI  - Development and characteristics of an adhesion bioassay for ectocarpoid algae.
AB  - Species of filamentous brown algae in the family Ectocarpaceae are significant
      members of fouling communities. However, there are few systematic studies on the
      influence of surface physico-chemical properties on their adhesion. In the
      present paper the development of a novel, laboratory-based adhesion bioassay for
      ectocarpoid algae, at an appropriate scale for the screening of sets of
      experimental samples in well-replicated and controlled experiments is described.
      The assays are based on the colonization of surfaces from a starting inoculum
      consisting of multicellular filaments obtained by blending the cultured alga
      Ectocarpus crouaniorum. The adhesion strength of the biomass after 14 days growth
      was assessed by applying a hydrodynamic shear stress. Results from adhesion tests
      on a set of standard surfaces showed that E. crouaniorum adhered more weakly to
      the amphiphilic Intersleek(r) 900 than to the more hydrophobic Intersleek(r) 700
      and Silastic(r) T2 coatings. Adhesion to hydrophilic glass was also weak. Similar
      results were obtained for other cultivated species of Ectocarpus but differed
      from those obtained with the related ectocarpoid species Hincksia secunda. The
      response of the ectocarpoid algae to the surfaces was also compared to that for
      the green alga, Ulva.

PMID- 22146004
TI  - Effects of drinking hydrogen-rich water on the quality of life of patients
      treated with radiotherapy for liver tumors.
AB  - BACKGROUND: Cancer patients receiving radiotherapy often experience fatigue and
      impaired quality of life (QOL). Many side effects of radiotherapy are believed to
      be associated with increased oxidative stress and inflammation due to the
      generation of reactive oxygen species during radiotherapy. Hydrogen can be
      administered as a therapeutic medical gas, has antioxidant properties, and
      reduces inflammation in tissues. This study examined whether hydrogen treatment,
      in the form of hydrogen-supplemented water, improved QOL in patients receiving
      radiotherapy. METHODS: A randomized, placebo-controlled study was performed to
      evaluate the effects of drinking hydrogen-rich water on 49 patients receiving
      radiotherapy for malignant liver tumors. Hydrogen-rich water was produced by
      placing a metallic magnesium stick into drinking water (final hydrogen
      concentration; 0.55~0.65 mM). The Korean version of the European Organization for
      Research and Treatment of Cancer's QLQ-C30 instrument was used to evaluate global
      health status and QOL. The concentration of derivatives of reactive oxidative
      metabolites and biological antioxidant power in the peripheral blood were
      assessed. RESULTS: The consumption of hydrogen-rich water for 6 weeks reduced
      reactive oxygen metabolites in the blood and maintained blood oxidation
      potential. QOL scores during radiotherapy were significantly improved in patients
      treated with hydrogen-rich water compared to patients receiving placebo water.
      There was no difference in tumor response to radiotherapy between the two groups.
      CONCLUSIONS: Daily consumption of hydrogen-rich water is a potentially novel,
      therapeutic strategy for improving QOL after radiation exposure. Consumption of
      hydrogen-rich water reduces the biological reaction to radiation-induced
      oxidative stress without compromising anti-tumor effects.

PMID- 22146005
TI  - Hurricane modification and adaptation in Miami-Dade County, Florida.
AB  - We investigate tropical cyclone wind and storm surge damage reduction for five
      areas along the Miami-Dade County coastline either by hardening buildings or by
      the hypothetical application of wind-wave pumps to modify storms. We calculate
      surge height and wind speed as functions of return period and sea surface
      temperature reduction by wind-wave pumps. We then estimate costs and economic
      losses with the FEMA HAZUS-MH MR3 damage model and census data on property at
      risk. All areas experience more surge damages for short return periods, and more
      wind damages for long periods. The return period at which the dominating hazard
      component switches depends on location. We also calculate the seasonal expected
      fraction of control damage for different scenarios to reduce damages. Surge
      damages are best reduced through a surge barrier. Wind damages are best reduced
      by a portfolio of techniques that, assuming they work and are correctly deployed,
      include wind-wave pumps.

PMID- 22146006
TI  - Development of a sensitive rRNA-targeted reverse transcription-quantitative
      polymerase chain reaction for detection of Vibrio cholerae/mimicus, V.
      parahaemolyticus/alginolyticus and Campylobacter jejuni/coli.
AB  - A sensitive rRNA-targeted reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR) method was developed for detection of Vibrio cholerae/mimicus,
      V. parahaemolyticus/alginolyticus and Campylobacter jejuni/coli by using specific
      primers. Counts of the enteric pathogens spiked in human stools were quantified
      at the lower detection limit of 10(3) cells/g stool by RT-qPCR, in marked
      contrast with conventional quantitative polymerase chain reaction (qPCR) at the
      detection limit of 10(5) to 10(6) cells/g stool. The bacterial counts determined
      by RT-qPCR were almost equivalent to those determined by the culture method and
      fluorescence in situ hybridization (FISH) during the course of in vitro culture.
      Bacterial rRNA in the stools was stable for at least 4 weeks when the stools were
      kept as the suspensions in RNA-stabilizing agent, RNAlater(r), even at 37(o) C.
      These data suggested that the rapid and high sensitive rRNA-targeted RT-qPCR was
      applicable for the accurate quantification of viable enteric pathogens, such as
      V. cholerae/mimicus, V. parahaemolyticus/alginolyticus and C. jejuni/coli.

PMID- 22146007
TI  - Asymmetric induction in 8pi electrocyclizations. Design of a removable chiral
      auxiliary.
AB  - The pseudo C(2) symmetric trans diphenyl oxazoline group acts as an effective
      chiral auxiliary in the 8pi, 6pi tandem electrocyclization of a substituted
      tetraene 1-carboxylic acid. Assignment of absolute stereochemistry to the [4.2.0]
      bicyclooctadiene product supports a model in which both s-cis and s-trans
      conformations favor the transition states with the same helical twist. This
      assignment prefaces the development of analogs of SNF4435 C and D. These natural
      products demonstrate activity as androgen receptor antagonists and as multidrug
      resistance (mdr) reversal agents.

PMID- 22146008
TI  - Searching the "biologically relevant"conformation of dopamine: a computational
      approach.
AB  - We report here an exhaustive and complete conformational study on the
      conformational potential energy hypersurface (PEHS) of dopamine (DA) interacting
      with the dopamine D2 receptor (D2-DR). A reduced 3D model for the binding pocket
      of the human D2-DR was constructed on the basis of the theoretical model
      structure of bacteriorhodopsin. In our reduced model system, only 13 amino acids
      were included to perform the quantum mechanics calculations. To obtain the
      different complexes of DA/D2-DR, we combined semiempirical (PM6), DFT (B3LYP/6
      31G(d)), and QTAIM calculations. The molecular flexibility of DA interacting with
      the D2-DR was evaluated from potential energy surfaces and potential energy
      curves. A comparative study between the molecular flexibility of DA in the gas
      phase and at D2-DR was carried out. In addition, several molecular dynamics
      simulations were carried out to evaluate the molecular flexibility of the
      different complexes obtained. Our results allow us to postulate the complexes of
      type A as the "biologically relevant conformations" of DA. In addition, the
      theoretical calculations reported here suggested that a mechanistic stepwise
      process takes place for DA in which the protonated nitrogen group (in any
      conformation) acts as the anchoring portion, and this process is followed by a
      rapid rearrangement of the conformation allowing the interaction of the
      catecholic OH groups.

PMID- 22146009
TI  - Ecological and socio-cultural factors influencing in situ conservation of crop
      diversity by traditional Andean households in Peru.
AB  - BACKGROUND: The Peruvian Andean region is a main center of plant domestication of
      the world. There, several tuber species were domesticated and the area lodges one
      of the most important reservoirs of their varieties and wild relatives. It is
      also the setting of traditional cultures using and conserving them. However, crop
      genetic erosion has been reported in the region since several decades ago;
      therefore, understanding factors influencing both loss and maintenance of crop
      variation is relevant to design conservation policies. Previous researches have
      examined factors influencing agrobiodiversity conservation in the region but
      additional case studies are recognized to be still necessary for a deeper
      understanding of causes of genetic erosion and for policy design to prevent and
      remedy it. Our study focused on analyzing (1) variation in richness of
      traditional varieties of tubers cultivated among households, (2) changes in
      varieties richness occurred in four consecutive agricultural cycles, and (3)
      ecological, social, and cultural factors influencing loss and conservation of
      varieties. METHODS: Richness of farmer varieties of tuber species cultivated by
      28 peasant households was monitored in communities of Cajamarca and Huanuco, Peru
      during four consecutive agricultural cycles (from 2001 to 2005). In-depth
      interviews were conducted with 12 of the households with higher reputation as
      conservationists, in order to document farmers' perception of tubers qualities in
      ecological, social, economic, technological and culinary aspects and how these
      influence their decisions of conservation priorities. Traditional varieties were
      identified according to their local names, which were then confronted among
      farmers and with scientific catalogues in order to identify synonyms. Based on
      the information documented, indexes of ecological and socio-cultural factors
      affecting agricultural practices were designed, and their linear correlations and
      multivariate relations with varieties richness managed per household were
      analyzed in order to explore factors with higher influence on conservation of
      crop variation. RESULTS: A total of 1483 and 507 farmer varieties of tuber
      species were found in the whole sample and period studied in Huanuco and
      Cajamarca, respectively. Significantly more varieties managed per household per
      year were recorded in Huanuco (146.39 +/- 12.02) than in Cajamarca (44.55 +/-
      9.26), and marked differences in number of varieties per year were documented
      among households within each region (78.25 to 246.50 in Huanuco, 7.50 to 144.00
      in Cajamarca). Correlation and multivariate analyses identified that the extent
      of agricultural area managed by households, cultural identity, practicing of
      traditional agricultural techniques, and level of self-sufficiency, are
      meaningful factors influencing higher varieties richness maintained by
      households. Yield and culinary attributes were considered by people as main
      features for selecting and deciding which varieties are priorities for
      conservation. CONCLUSIONS: Maintenance and promotion of indigenous Andean culture
      is crucial for ensuring conservation of both traditional agroecological systems
      and agrobiodiversity. Policies supporting Andean culture (through educational,
      cultural and economic programs) are therefore directly connected with
      conservation of traditional farmer varieties. Promotion of seed availability and
      interchange are effective actions for maintaining and developing diversity, but
      using and valuing native tubers at regional, national and international levels
      are fundamental motivations to enhance policies and processes in this direction.

PMID- 22146010
TI  - Aberrant DNA methylation profile in pleural fluid for differential diagnosis of
      malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) usually develops pleural fluid. We
      investigated the value of DNA methylation in the pleural fluid for
      differentiating MPM from lung cancer (LC). Pleural fluid was collected from 39
      patients with MPM, 46 with LC, 25 with benign asbestos pleurisy (BAP) and 30 with
      other causes. The methylation of O(6)-methylguanine-DNA methyltransferase (MGMT),
      p16(INK4a) , ras association domain family 1A (RASSF1A), death-associated protein
      kinase (DAPK), and retinoic acid receptor beta (RARbeta) was examined using
      quantitative real-time PCR. DNA methylation of RASSF1A, p16(INK4a), RARbeta, MGMT
      and DAPK was detected in 12 (30.8%), 3 (7.7%), 11 (28.2%), 0 (0.0%) and five
      patients (12.8%) with MPM, and in 22 (47.8%), 14 (30.4%), 24 (52.2%), 1 (2.2%)
      and six patients (13.0%) with LC, respectively. The mean methylation ratios of
      RASSF1A, p16(INK4a) and RARbeta were 0.37 (range 0.0-2.84), 0.11 (0.0-2.67) and
      0.44 (0.0-3.32) in MPM, and 0.87 (0.0-3.14), 1.16 (0.0-5.35) and 1.69 (0.0-6.49)
      in LC, respectively. The methylation ratios for the three genes were
      significantly higher in LC than in MPM (RASSF1A, P = 0.039; p16(INK4a), P =
      0.005; and RARbeta, P = 0.002). Patients with methylation in at least one gene
      were 3.51 (95% confidence interval, 1.09-11.34) times more likely to have LC.
      Hypermethylation seemed no greater with MPM than with BAP. Extended exposure to
      asbestos (?30 years) was correlated with an increased methylation frequency (P =
      0.020). Hypermethylation of tumor suppressor genes in pleural fluid DNA has the
      potential to be a valuable marker for differentiating MPM from LC.

PMID- 22146011
TI  - Location of the synaptosome-binding regions on botulinum neurotoxin B.
AB  - The regions of botulinum neurotoxin B (BoNT/B) involved in binding to mouse brain
      synaptosomes (snps) were localized. Sixty 19-residue overlapping peptides
      (peptide C31 consisted of 24 residues) encompassing BoNT/B H chain (residues 442
      1291) were synthesized and used to inhibit binding of (125)I-labeled BoNT/B to
      snps. Synaptosome-binding regions were noncompeting and existed on both H(N) and
      H(C) domains of neurotoxin. At 37  degrees C, inhibitory activities on H(N)
      resided, in decreasing order, in peptides 638-656 (26.7%), 596-614 (18.2%), 512
      530 (13.9%), 778-796 (13.8%), and 526-544 (11.6%). On H(C), activity resided in
      decreasing order in peptides 1170-1188 (44.6%), 1128-1146 (21.6%), 1184-1202
      (18.6%), 1156-1174 (13.0%), 946-964 (11.8%), 1114-1132 (11.2%), 1100-1118 (6.2%),
      876-894 (6.1%), 1268-1291 (4.6%), and 1226-1244 (4.3%). The 45 remaining H(N) and
      H(C) peptides had no activity. At 4  degrees C, peptide C24 (1170-1188) remained
      quite active (inhibiting, 31.2%), while activities of peptides N15, C21, and C25
      were little under 10%. The snp-binding regions contained sites that bind
      synaptotagmin II and gangliosides. Despite the low degree of sequence homology,
      BoNT/B and BoNT/A display significant structural homology and appeared to bind in
      part to the same snp-binding regions. Binding of each labeled toxin to snps was
      inhibited ~50% by the other toxin, 70-72% by its correlate H(C), and by the H(C)
      of the other toxin [29% (BoNT/A by H(C) of B) or 32% (BoNT/B by H(C) of A)]. In
      the three-dimensional structure of BoNT/B, the greater part of H(C), one H(N)
      face, and part of the belt on the same side interact with snps. Thus, BoNT/B
      binds to snps through the H(C) head and employs regions on one H(N) face and the
      belt, reserving flexibility for the belt's unbound part to release the light
      chain. Most snp-binding regions coincide or overlap with blocking antibody (Ab)
      binding regions explaining how such Abs prevent BoNT/B toxicity.

PMID- 22146012
TI  - Role of PufX in photochemical charge separation in the RC-LH1 complex from
      Rhodobacter sphaeroides: an ultrafast mid-IR pump-probe Investigation.
AB  - Photochemical charge separation in isolated reaction center-light harvesting 1
      (RC-LH1) complexes from Rhodobacter sphaeroides was examined using time-resolved
      mid-infrared pump-probe spectroscopy. Absorption difference spectra were recorded
      between 1760 and 1610 cm(-1) with subpicosecond time resolution to characterize
      excited-state and radical pair dynamics in these complexes, via the induced
      absorption changes in the keto carbonyl modes of the bacteriochlorophylls and
      bacteriopheophytins. Experiments on RC-LH1 complexes with and without the
      polypeptide PufX show that its presence is required to achieve generation of the
      radical pair P(+)Q(A)(-) under mildly reducing conditions. In the presence of
      PufX, the final radical pair formed over a ~3 ns period was P(+)Q(A)(-), but in
      its absence the corresponding radical pair was P(+)H(A)(-), implying that Q(A)
      was either absent in these PufX-deficient complexes or was prereduced. However,
      P(+)Q(A)(-) could be generated in PufX-deficient complexes following addition of
      the oxidant DMSO, showing that Q(A) was present in these complexes and allowing
      the conclusion that under mildly reducing conditions charge separation was
      blocked after P(+)H(A)(-) due to the presence of an electron on Q(A). The data
      provide strong support for the hypothesis that one of the functions of PufX is to
      regulate the stability of Q(B)(-), ensuring the oxidation of Q(A)(-) in the
      presence of a reduced quinone pool and so preserving efficient photochemical
      charge separation under anaerobic conditions.

PMID- 22146013
TI  - Atmospheric chemistry of isoflurane, desflurane, and sevoflurane: kinetics and
      mechanisms of reactions with chlorine atoms and OH radicals and global warming
      potentials.
AB  - The smog chamber/Fourier-transform infrared spectroscopy (FTIR) technique was
      used to measure the rate coefficients k(Cl + CF(3)CHClOCHF(2), isoflurane) = (4.5
      +/- 0.8) * 10(-15), k(Cl + CF(3)CHFOCHF(2), desflurane) = (1.0 +/- 0.3) * 10(
      15), k(Cl + (CF(3))(2)CHOCH(2)F, sevoflurane) = (1.1 +/- 0.1) * 10(-13), and k(OH
      + (CF(3))(2)CHOCH(2)F) = (3.5 +/- 0.7) * 10(-14) cm(3) molecule(-1) in 700 Torr
      of N(2)/air diluent at 295 +/- 2 K. An upper limit of 6 * 10(-17) cm(3) molecule(
      1) was established for k(Cl + (CF(3))(2)CHOC(O)F). The laser photolysis/laser
      induced fluorescence (LP/LIF) technique was employed to determine hydroxyl
      radical rate coefficients as a function of temperature (241-298 K): k(OH +
      CF(3)CHFOCHF(2)) = (7.05 +/- 1.80) * 10(-13) exp[-(1551 +/- 72)/T] cm(3)
      molecule(-1); k(296 +/- 1 K) = (3.73 +/- 0.08) * 10(-15) cm(3) molecule(-1), and
      k(OH + (CF(3))(2)CHOCH(2)F) = (9.98 +/- 3.24) * 10(-13) exp[-(969 +/- 82)/T]
      cm(3) molecule(-1); k(298 +/- 1 K) = (3.94 +/- 0.30) * 10(-14) cm(3) molecule(
      1). The rate coefficient of k(OH + CF(3)CHClOCHF(2), 296 +/- 1 K) = (1.45 +/-
      0.16) * 10(-14) cm(3) molecule(-1) was also determined. Chlorine atoms react with
      CF(3)CHFOCHF(2) via H-abstraction to give CF(3)CFOCHF(2) and CF(3)CHFOCF(2)
      radicals in yields of approximately 83% and 17%. The major atmospheric fate of
      the CF(3)C(O)FOCHF(2) alkoxy radical is decomposition via elimination of CF(3) to
      give FC(O)OCHF(2) and is unaffected by the method used to generate the
      CF(3)C(O)FOCHF(2) radicals. CF(3)CHFOCF(2) radicals add O(2) and are converted by
      subsequent reactions into CF(3)CHFOCF(2)O alkoxy radicals, which decompose to
      give COF(2) and CF(3)CHFO radicals. In 700 Torr of air 82% of CF(3)CHFO radicals
      undergo C-C scission to yield HC(O)F and CF(3) radicals with the remaining 18%
      reacting with O(2) to give CF(3)C(O)F. Atmospheric oxidation of
      (CF(3))(2)CHOCH(2)F gives (CF(3))(2)CHOC(O)F in a molar yield of 93 +/- 6% with
      CF(3)C(O)CF(3) and HCOF as minor products. The IR spectra of (CF(3))(2)CHOC(O)F
      and FC(O)OCHF(2) are reported for the first time. The atmospheric lifetimes of
      CF(3)CHClOCHF(2), CF(3)CHFOCHF(2), and (CF(3))(2)CHOCH(2)F (sevoflurane) are
      estimated at 3.2, 14, and 1.1 years, respectively. The 100 year time horizon
      global warming potentials of isoflurane, desflurane, and sevoflurane are 510,
      2540, and 130, respectively. The atmospheric degradation products of these
      anesthetics are not of environmental concern.

PMID- 22146014
TI  - Streptococcus agalactiae, an emerging pathogen for cultured ya-fish, Schizothorax
      prenanti, in China.
AB  - Streptococcus agalactiae (Group B streptococcus) has emerged as an important
      pathogen that affects humans and animals, including aquatic species. S.
      agalactiae infections are becoming an increasing problem in aquaculture and have
      been reported worldwide in a variety of fish species, especially those living in
      warm water. Recently, a very serious infectious disease of unknown aetiology
      broke out in ya-fish (Schizothorax prenanti) farms in Sichuan Province. A Gram
      positive, chain-forming coccus was isolated from moribund cultured ya-fish. The
      goals of this study were to identify the bacterial strains isolated from diseased
      fish between 2009 and 2011 in Sichuan Province, China, to evaluate the
      pathogenicity of the pathogen in ya-fish, crucian carp (Carassius carassius) and
      the Nile tilapia (Oreochromis niloticus); and to determine the susceptibility of
      the pathogen strains to many currently available anti-microbial agents. The
      virulence tests were conducted by intraperitoneal injection of bacterial
      suspensions. In this study, four strains of a Gram-positive, chain-forming coccus
      were isolated from moribund cultured ya-fish (S. prenanti). The coccoid
      microorganism was identified as S. agalactiae using a commercial streptococcal
      grouping kit and 16S rDNA sequencing analysis. Susceptibility of the isolates to
      22 antibiotics was tested using the disc diffusion method. All isolates showed a
      similar antibiotic susceptibility, which were sensitive to amoxicillin,
      ciprofloxacin, lomefloxacin, chloramphenicol, rifampin, vancomycin, azithromycin,
      florfenicol, cefalexin, cefradine and deoxycycline and resistant to gentamicin,
      sinomin (SMZ/TMP), penicillin, tenemycin, fradiomycin and streptomycin.
      Furthermore, the virulence tests were conducted by intraperitoneal injection of
      the isolated strain GY101 in ya-fish, crucian carp and the Nile tilapia. This
      coccus was lethal to ya-fish, Nile tilapia and crucian carp. The mortality rates
      of infected ya-fish were 100%, 100%, 60% and 20% at doses of 1.0 * 107, 1.0 *
      106, 1.0 * 105 and 1.0 * 104 CFU/fish, respectively. The values were 100%, 80%,
      60% and 30% for Nile tilapia and 100%, 60%, 10% and 0% for crucian carp. To our
      knowledge, this is the first report of S. agalactiae as a pathogen of ya-fish.

PMID- 22146016
TI  - Single-port laparoscopic floppy Nissen fundoplication: a novel technique with the
      aid of the Cerrahpasa retractor.
AB  - With the advent of single-port laparoscopy, the spectrum of abdominal surgeries
      performed is widening. The retraction of the left lobe of the liver in the upper
      gastrointestinal procedures is a critical maneuver with its added possible
      complications. In our study, we used the Cerrahpasa retractor (trademark pending
      by E. Eyuboglu and T. Ipek) for the retraction of the left liver in 22 patients
      with a different concept other than using the suturing or silk lace techniques
      described in previous studies. In our technique, the potential of tearing the
      liver or other anatomical structures is minimal. We believe that, with the aid of
      our Cerrahpasa retractor, the problem of liver retraction is being solved by a
      simple and safe technique.

PMID- 22146015
TI  - Field and laboratory studies on the bioconversion of coal to methane in the San
      Juan Basin.
AB  - The bioconversion of coal to methane in the San Juan Basin, New Mexico, was
      investigated. Production waters were analyzed via enrichment studies, metabolite
      profiling, and culture-independent methods. Analysis of 16S rRNA gene sequences
      indicated the presence of methanogens potentially capable of acetoclastic,
      hydrogenotrophic, and methylotrophic metabolisms, predominantly belonging to the
      Methanosarcinales and Methanomicrobiales. Incubations of produced water and coal
      readily produced methane, but there was no correlation between the thermal
      maturity and methanogenesis. Coal methanogenesis was greater when samples with a
      greater richness of Firmicutes were utilized. A greater archaeal diversity was
      observed in the presence of several aromatic and short-chain fatty acid
      metabolites. Incubations amended with lactate, hydrogen, formate, and short-chain
      alcohols produced methane above un-amended controls. Methanogenesis from acetate
      was not observed. Metabolite profiling showed the widespread occurrence of
      putative aromatic ring intermediates including benzoate, toluic acids, phthalic
      acids, and cresols. The detection of saturated and unsaturated alkylsuccinic
      acids indicated n-alkane and cyclic alkane/alkene metabolism. Microarray analysis
      complemented observations based on hybridization to functional genes related to
      the anaerobic metabolism of aromatic and aliphatic substrates. These data suggest
      that coal methanogenesis is unlikely to be limited by methanogen biomass, but
      rather the activation and degradation of coal constituents.

PMID- 22146017
TI  - Effect of silodosin on detrusor overactivity in the male spontaneously
      hypertensive rat.
AB  - Recently, several studies have suggested that detrusor overactivity (DO) is the
      result of bladder ischaemia. Hypertension could affect pelvic arterial blood
      flow, resulting in loss of smooth muscle in the bladder with resultant loss of
      bladder compliance. Spontaneously hypertensive rats are considered a valuable
      tool for exploring the pathogenesis of DO. Some reports indicate that alpha(1)
      adrenoceptor antagonists improve chronic ischaemia of the lower urinary tract in
      patients with LUTS, with concomitant improvement of their symptoms as well as
      improvement of DO through an increased bladder blood flow (BBF) in the rat with
      bladder outlet obstruction. However, the mechanism of improvement of silodosin on
      storage or irritative symptoms is not well investigated and is still unclear.
      Silodosin prevents hypertension-related DO in the SHR via several possible
      mechanisms. One possible mechanism of the efficacy of silodosin to the DO
      includes the improvement of the BBF. OBJECTIVE: To investigate the effect of the
      alpha(1A) selective adrenoceptor antagonist, silodosin, on hypertension-related
      detrusor overactivity (DO) and its possible mechanism in spontaneously
      hypertensive rats (SHRs). MATERIALS AND METHODS: Twelve-week-old male SHRs
      received treatment with silodosin (100 ug/kg perorally) once daily for 6 weeks;
      vehicle-treated Wistar rats and vehicle-treated SHRs were used for our study. Six
      weeks after silodosin treatment, voiding functions were estimated by voiding
      behaviour and cystometric studies in all groups. The bladder blood flow was
      measured by the hydrogen clearance method, and tissue levels of nerve growth
      factor (NGF) and calcitonin gene-related peptide (CGRP) were measured by enzyme
      linked immunosorbent assay (ELISA). Furthermore, the expressions of alpha1
      adrenoceptor subtype mRNAs in the bladder were investigated by real-time PCR
      method. RESULTS: The SHRs showed significant increases in blood pressure,
      micturition frequency and tissue levels of NGF and CGRP in the bladder. Moreover,
      the SHRs showed significant decreases in bladder blood flow and single voided
      volume estimated by both voiding behaviour and cystometric studies compared with
      those in the Wistar rats. Six weeks of treatment with silodosin significantly
      ameliorated hypertension-related alterations of these variables with concomitant
      small changes of blood pressure. The expression levels of alpha1 adrenoceptor
      subtype mRNAs in the bladder were similar in all the groups and the rank order
      was alpha1A = alpha1D > alpha1B in all groups. However, there were no significant
      differences in the expressions of alpha(1A) adrenoceptor mRNAs between any
      groups. CONCLUSION: The data in the present study suggest that silodosin
      normalizes hypertension-related DO in SHRs, which could be related to its effect
      on the increased blood flow in the bladder.

PMID- 22146018
TI  - Personalities, politics, and bioethics.

PMID- 22146019
TI  - Dead man walking-politics, Sr. Helen Prejean, and the vocation of the
      bioethicist.

PMID- 22146020
TI  - The political satirist as public intellectual: the case of Jon Stewart.

PMID- 22146021
TI  - William B. Hurlbut: Building a bridge over troubled stem cell waters.

PMID- 22146022
TI  - Toward a "magenta" public bioethics discourse--Bart Stupak and health care
      reform.

PMID- 22146023
TI  - Reason giving: when public leaders ignore evidence.

PMID- 22146024
TI  - Sense and nonsense in the conservative critique of Obamacare.

PMID- 22146025
TI  - What's wrong with chemoprevention of prostate cancer?
AB  - When prostate-specific antigen (PSA) testing was introduced, proponents expected
      it to cut prostate-cancer mortality and did not expect it to unleash an epidemic
      of unnecessary treatments. Now that evidence of a mortality benefit remains
      unclear while evidence of overtreatment in undeniable, there is understandable
      interest in reducing the human costs of the PSA system. Two related drugs,
      finasteride and dutasteride, both proven to reduce the incidence of prostate
      cancer and the "risk of diagnosis," are being promoted accordingly. However, if
      not for the flaws of the PSA system the use of these drugs for purposes of
      prevention would lose its rationale. Not only are the drugs in this sense
      dependent on a faulty system, but their own mortality benefits are as speculative
      as PSA's-in addition to which, they introduce new risks.

PMID- 22146026
TI  - Good ethics begins with sound medicine: prostate cancer screening and
      chemoprevention.

PMID- 22146027
TI  - A rational basis for chemoprevention of prostate cancer.

PMID- 22146028
TI  - Prostate cancer prevention: do the 5-ARIs make the grade?
AB  - Although imperfect, PSA testing is here to stay. Men who undergo PSA testing
      should do so with an understanding of the potential benefits (decreased prostate
      cancer mortality) and known risks (increased likelihood of being diagnosed with
      prostate cancer) of screening. The diagnosis of prostate cancer often leads to
      radical therapy in men who would never have known they had the disease if not for
      early detection. Although it is possible that 5-ARIs may occasionally cause a
      high-grade prostate cancer, the magnitude of this potential harm is likely to be
      tempered by earlier detection. Also balancing this potential harm is the well
      established fact that the 5-ARIs decrease the likelihood that a man who desires
      PSA testing will become a prostate cancer patient. These are admittedly difficult
      risk-risk calculations. However, to suggest that only "unambiguously safe" drugs
      should be approved for cancer risk reduction sets a standard that can only be met
      by homeopathic nostrums. That is not the standard to which we should aspire.

PMID- 22146029
TI  - Problems with prioritization: exploring ethical solutions to inequalities in HIV
      care.
AB  - Enormous gaps between HIV burden and health care availability in low-income
      countries raise severe ethical problems. This article analyzes four HIV-priority
      dilemmas with interest across contexts and health systems. We explore principled
      distributive conflicts and use the Atkinson index to make explicit trade-offs
      between health maximization and equality in health. We find that societies need a
      relatively low aversion to inequality to favor treatment for children, even with
      large weights assigned to extending the lives of adults: higher inequality
      aversion is needed to share resources equally between high-cost and low-cost
      treatment; higher inequality aversion is needed to favor treatment rather than
      prevention, and the highest inequality aversion is needed to favor sharing
      treatment between urban and rural regions rather than urban provision of
      treatment. This type of ethical sensitivity analysis may clarify the ethics of
      health policy choice.

PMID- 22146030
TI  - Two sorts of health maximization: average view and total view.

PMID- 22146031
TI  - Inequalities in HIV care: chances versus outcomes.

PMID- 22146032
TI  - Creating moral conflict through an inequality sensitive summary measure.

PMID- 22146033
TI  - A step toward pluralist fairness.

PMID- 22146034
TI  - Treatment-as-prevention needs to be considered in the just allocation of HIV
      drugs.

PMID- 22146035
TI  - Obstetricians and violence against women.
AB  - I argue that the American Congress of Obstetricians and Gynecologists (ACOG), as
      an organization and through its individual members, can and should be a far
      greater ally in the prevention of violence against women. Specifically, I argue
      that we need to pay attention to obstetrical practices that inadvertently
      contribute to the problem of violence against women. While intimate partner
      violence is a complex phenomenon, I focus on the coercive control of women and
      adherence to oppressive gender norms. Using physician response to alcohol use
      during pregnancy and court-ordered medical treatment as examples, I show how some
      obstetrical practices mirror the attitudes of abusive men insofar as they try to
      coercively control women's behavior through manipulation and violence. To be
      greater allies in the prevention of violence against women, obstetricians should
      stop participating in practices that inadvertently perpetuate violence against
      women.

PMID- 22146036
TI  - Obstetricians: women's advocates, not adversaries.

PMID- 22146037
TI  - A case study in junk bioethics run amok.

PMID- 22146038
TI  - Power in practice: best interests or coercive control?

PMID- 22146039
TI  - Polemics and pregnancy: a response to arguments about ethical obstetrical care.

PMID- 22146040
TI  - In the face of uncertainty about the risks of low-level drinking, abstinence is
      prudent, not misogynistic, advice.

PMID- 22146041
TI  - Informed passion: addressing the intersection of violence against women and
      contemporary obstetrical practice.

PMID- 22146042
TI  - Meeting the doctor with my clothes on.

PMID- 22146043
TI  - Withholding or necessary filtering of information?

PMID- 22146047
TI  - Forfeited health: response to open peer commentaries on "What's wrong with
      chemoprevention of prostate cancer?".

PMID- 22146048
TI  - Gender identity disorder in twins: a review of the case report literature.
AB  - INTRODUCTION: The etiology of gender identity disorder (GID) remains largely
      unknown. In recent literature, increased attention has been attributed to
      possible biological factors in addition to psychological variables. AIM: To
      review the current literature on case studies of twins concordant or discordant
      for GID. METHODS: A systematic, comprehensive literature review. RESULTS: Of 23
      monozygotic female and male twins, nine (39.1%) were concordant for GID; in
      contrast, none of the 21 same-sex dizygotic female and male twins were concordant
      for GID, a statistically significant difference (P=0.005). Of the seven opposite
      sex twins, all were discordant for GID. CONCLUSIONS: These findings suggest a
      role for genetic factors in the development of GID.

PMID- 22146050
TI  - Implementing a smoking cessation program in social and community service
      organisations: a feasibility and acceptability trial.
AB  - INTRODUCTION AND AIMS: Novel ways of accessing and engaging smokers who are
      socially and economically disadvantaged may help reduce socioeconomic disparities
      in smoking rates. This study assessed the feasibility and acceptability of
      integrating smoking cessation support into usual care at a social and community
      service organisation (SCSO). DESIGN AND METHODS: One SCSO providing a Personal
      Helpers and Mentors program participated. Support workers were provided with
      training in 5A's, brief motivational interviewing and use of nicotine replacement
      therapy, and then recruited clients into a 6 month smoking program. Acceptability
      and feasibility was assessed prior to receiving training and at 3 and 6 month
      follow up for support workers, and at enrolment into the program and at 4 and 6
      month follow up for clients. RESULTS: Six support workers (67%) and 20 of their
      clients (65%) took part. Overall acceptability of the program was high,
      particularly among clients. The amount of time spent talking about smoking
      increased from 3.8 min per visit at baseline to 15.5 min at 6 month follow up.
      There was a significant reduction in the number of cigarettes smoked from 20.5
      cigarettes per day at baseline to 15 cigarettes per day at 6 month follow up (P =
      0.04). DISCUSSION AND CONCLUSIONS: SCSOs are both interested in and capable of
      providing smoking care and the majority of clients found the smoking cessation
      intervention acceptable and helpful. Given the demonstrated acceptability and
      feasibility of this approach, further research to determine the effectiveness of
      this approach is warranted.

PMID- 22146049
TI  - Real-time molecular imaging of tricarboxylic acid cycle metabolism in vivo by
      hyperpolarized 1-(13)C diethyl succinate.
AB  - The Krebs tricarboxylic acid cycle (TCA) is central to metabolic energy
      production and is known to be altered in many disease states. Real-time molecular
      imaging of the TCA cycle in vivo will be important in understanding the metabolic
      basis of several diseases. Positron emission tomography (PET) with FDG-glucose (2
      [(18)F]fluoro-2-deoxy-d-glucose) is already being used as a metabolic imaging
      agent in clinics. However, FDG-glucose does not reveal anything past glucose
      uptake and phosphorylation. We have developed a new metabolic imaging agent,
      hyperpolarized diethyl succinate-1-(13)C-2,3-d(2) , that allows for real-time in
      vivo imaging and spectroscopy of the TCA cycle. Diethyl succinate can be
      hyperpolarized via parahydrogen-induced polarization (PHIP) in an aqueous
      solution with signal enhancement of 5000 compared to Boltzmann polarization.
      (13)C magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI)
      were achieved in vivo seconds after injection of 10-20 MUmol of hyperpolarized
      diethyl succinate into normal mice. The downstream metabolites of hyperpolarized
      diethyl succinate were identified in vivo as malate, succinate, fumarate, and
      aspartate. The metabolism of diethyl succinate was altered after exposing the
      animal to 3-nitropropionate, a known irreversible inhibitor of succinate
      dehydrogenase. On the basis of our results, hyperpolarized diethyl succinate
      allows for real-time in vivo MRI and MRS with a high signal-to-noise ratio and
      with visualization of multiple steps of the TCA cycle. Hyperpolarization of
      diethyl succinate and its in vivo applications may reveal an entirely new regime
      wherein the local status of TCA cycle metabolism is interrogated on the time
      scale of seconds to minutes with unprecedented chemical specificity and MR
      sensitivity.

PMID- 22146051
TI  - The crystal structure of protease Sapp1p from Candida parapsilosis in complex
      with the HIV protease inhibitor ritonavir.
AB  - Secreted aspartic proteases (Saps) are extracellular proteolytic enzymes that
      enhance the virulence of Candida pathogens. These enzymes therefore represent
      possible targets for therapeutic drug design. Saps are inhibited by nanomolar
      concentrations of the classical inhibitor of aspartic proteases pepstatin A and
      also by the inhibitors of the HIV protease, but with the K(i) of micromolar
      values or higher. To contribute to the discussion regarding whether HIV protease
      inhibitors can act against opportunistic mycoses by the inhibition of Saps, we
      determined the structure of Sapp1p from Candida parapsilosis in complex with
      ritonavir (RTV), a clinically used inhibitor of the HIV protease. The crystal
      structure refined at resolution 2.4 A proved binding of RTV into the active site
      of Sapp1p and provided the structural information necessary to evaluate the
      stability and specificity of the protein-inhibitor interaction.

PMID- 22146053
TI  - The Global Online Sexuality Survey (GOSS): female sexual dysfunction among
      Internet users in the reproductive age group in the Middle East.
AB  - INTRODUCTION: The exact prevalence of female sexual dysfunction (FSD) in the
      Middle East is exceptionally difficult to measure in light of its sensitive
      nature and the conservative tinge of the population. AIM: The Global Online
      Sexuality Survey-Arabic-Females (GOSS-AR-F) is a community-based study of female
      sexuality in the Middle East through an online survey. MAIN OUTCOME MEASURES:
      Prevalence of risk for female sexual dysfunction (rFSD) in the reproductive age
      group and its vulnerability to various risk factors. METHODS: GOSS-AR-F was
      offered via online advertising. The survey is comprised of the Female Sexual
      Function Index (FSFI) questionnaire among other questions. RESULTS: Out of 2,920
      participants, 344 participants completed all survey questions. Average total FSFI
      score was 23 +/- 6.5, with 59.1% of participants suffering rFSD. Age adjusted
      prevalence of rFSD was 59.5%, standardized to World Health Organization World
      Standard Population. There was a statistically significant higher prevalence of
      rFSD among cases with subjectively reported depression and male partner-related
      shortcomings such as erectile dysfunction and premature ejaculation as reported
      by the female participant, in addition to dissatisfaction with partner's penile
      size, insufficient foreplay, and practice of masturbation. This was not the case
      with advancing age, diabetes mellitus, hypertension, smoking, ongoing pregnancy,
      mode of previous child delivery, infertility, menstrual irregularities,
      dysmenorrhea, interpersonal distress, subjectively reported hirsutism, and female
      genital cutting. Participants were found to require longer duration of coitus and
      better ejaculatory control but not necessarily a higher coital frequency.
      CONCLUSION: Female sexual function in the reproductive age appears to be
      adversely affected by psychological factors and shortcomings in male sexual
      function more than anything. These findings point to the possibility that many
      cases of FSD can be managed with the focus on male partner's ailments and
      attitudes that are relatively easier to manage.

PMID- 22146054
TI  - Neonatal bleeding in haemophilia: a European cohort study.
AB  - Birth is the first haemostatic challenge for a child with haemophilia. Our aim
      was to examine the association between perinatal risk factors and major neonatal
      bleeding in infants with haemophilia. This observational cohort study in 12
      European haemophilia treatment centres (HTC) incorporated 508 children with
      haemophilia A or B, born between 1990 and 2008. Risk factors for bleeding were
      analysed by univariate analysis. Head bleeds occurred in 18 (3.5%) children
      within the first 28 d of life, including three intraparenchymal bleeds, one
      subdural haematoma and 14 cephalohaematomas. Intra-cranial bleeds were associated
      with long-term neurological sequelae in two (0.4%) cases; no deaths occurred.
      Assisted delivery (forceps/vacuum) was the only risk factor for neonatal head
      bleeding [Odds Ratio (OR) 8.84: 95% confidence interval (CI) 3.05-25.61]. Mild
      haemophilia and maternal awareness of her haemophilia carrier status seemed to be
      protective (OR 0.24; 95%CI 0.05-1.05 and OR 0.34; 95%CI 0.10-1.21, respectively),
      but due to the low number of events this was not statistically significant. We
      found no association between neonatal head bleeding and country, maternal age,
      parity, gestational age or presence of HTC. Maternal awareness of carrier status
      protected against assisted delivery (unadjusted OR 0.37; 95%CI 0.15-0.90;
      adjusted OR 0.47 (95%CI 0.18-1.21).

PMID- 22146055
TI  - Peroxides and peroxidases in the endoplasmic reticulum: integrating redox
      homeostasis and oxidative folding.
AB  - SIGNIFICANCE: The endoplasmic reticulum (ER), the port of entry into the
      secretory pathway, is a complex organelle that performs many fundamental
      functions, including protein synthesis and quality control, Ca(2+) storage and
      signaling. Redox homeostasis is of paramount importance for allowing the
      efficient folding of secretory proteins, most of which contain essential
      disulfide bonds. RECENT ADVANCES: revealed that an intricate protein network
      sustains the processes of disulfide bond formation and reshuffling in the ER.
      Remarkably, H(2)O(2), which is a known by-product of Ero1 flavoproteins in cells,
      is utilized by peroxiredoxin-4 and glutathione peroxidases-7 and -8, which reside
      in the mammalian secretory compartment and further fuel oxidative protein folding
      while limiting oxidative damage. CRITICAL ISSUES: that remain to be addressed are
      the sources, diffusibility and signaling role(s) of H(2)O(2) in and between
      organelles and cells, how the emerging redundancy in the systems is coupled to
      precise regulation, and how the distinct pathways operating in the early
      secretory compartment are integrated with one another. FUTURE DIRECTIONS: A
      further dissection of the pathways that integrate folding, redox homeostasis, and
      signaling in the early secretory pathway may allow to manipulate protein
      homeostasis and survival-death decisions in degenerative diseases or cancer.

PMID- 22146056
TI  - The sacred and the absurd--an electrophysiological study of counterintuitive
      ideas (at sentence level).
AB  - Religious beliefs are both catchy and durable: they exhibit a high degree of
      adherence to our cognitive system, given their success of transmission and
      spreading throughout history. A prominent explanation for religion's cultural
      success comes from the "MCI hypothesis," according to which religious beliefs are
      both easy to recall and desirable to transmit because they are minimally
      counterintuitive (MCI). This hypothesis has been empirically tested at concept
      and narrative levels by recall measures. However, the neural correlates of MCI
      concepts remain poorly understood. We used the N400 component of the event
      related brain potential as a measure of counterintuitiveness of violations
      comparing religious and non-religious sentences, both counterintuitive, when
      presented in isolation. Around 80% in either condition were core-knowledge
      violations. We found smaller N400 amplitudes for religious as compared to non
      religious counterintuitive ideas, suggesting that religious ideas are less
      semantically anomalous. Moreover, behavioral measures revealed that religious
      ideas are not readily detected as unacceptable. Finally, systematic analyses of
      our materials, according to conceptual features proposed in cognitive models of
      religion, did not reveal any outstanding variable significantly contributing to
      these differences. Refinements of cognitive models of religion should elucidate
      which combination of factors renders an anomaly less counterintuitive and thus
      more suitable for recall and transmission.

PMID- 22146057
TI  - Patient/caregiver perceived benefits and barriers to elective orthopedic surgery
      (EOS) in patients with congenital hemophilia with inhibitors.
AB  - OBJECTIVE: Congenital hemophilia patients with inhibitors are at greater risk for
      developing arthropathy and orthopedic complications compared to those without
      inhibitors. Elective orthopedic surgeries (EOS) may be an option for these
      patients and may provide long-term cost savings due to reduced bleed frequency.
      However, patient motivations and goals for undergoing or delaying such surgeries
      are not well understood. A US-based patient/caregiver survey was designed to
      describe inhibitor patient experiences and outcomes following EOS and to develop
      a comprehensive understanding of patient preferences for EOS, which are lacking
      in the literature. METHODS: The paper-pencil questionnaire was mailed to 261 US
      inhibitor patients/caregivers and included history and timing of EOS, quality-of
      life (QoL) and potential benefits of and barriers to receiving EOS.
      Univariate/bivariate descriptive analyses were performed to characterize those
      with/without a history of EOS. RESULTS: For 103 subjects who responded, the mean
      age was 20.9 years. Approximately 25% (n = 26) of respondents underwent EOS, most
      commonly on the knee (21, 81%); 73.1% of surgery recipients reported the surgery
      improved or greatly improved their QoL based on single-item response. The highest
      ranked perceived benefits were less pain, fewer bleeds, and improved mobility.
      However, the leading concerns reported were lack of improved mobility (62.2%),
      fear of uncontrolled bleeding (61.3%), and surgical complications, such as blood
      clot (60.0%). LIMITATIONS: The study consisted of a small sample size, primarily
      due to the difficulty in trying to reach inhibitor patients or their caregivers,
      thereby restricting inferential and stratification analysis. CONCLUSIONS: QoL
      improved for most inhibitor patients who reported having EOS. For those
      considering surgery, there is optimism about the potential benefits, but
      realistic concerns associated with bleed control and post-op complications.

PMID- 22146058
TI  - Changes in stomatal conductance along grass blades reflect changes in leaf
      structure.
AB  - Identifying the consequences of grass blade morphology (long, narrow leaves) on
      the heterogeneity of gas exchange is fundamental to an understanding of the
      physiology of this growth form. We examined acropetal changes in anatomy,
      hydraulic conductivity and rates of gas exchange in five grass species (including
      C(3)  and C(4)  functional types). Both stomatal conductance and photosynthesis
      increased along all grass blades despite constant light availability. Hydraulic
      efficiency within the xylem remained constant along the leaf, but structural
      changes outside the xylem changed in concert with stomatal conductance. Stomatal
      density and stomatal pore index remained constant along grass blades but
      interveinal distance decreased acropetally resulting in a decreased path length
      for water movement from vascular bundle to stomate. The increase in stomatal
      conductance was correlated with the decreased path length through the leaf
      mesophyll. A strong correlation between the distance from vascular bundles to
      stomatal pores and stomatal conductance has been identified across species; our
      results suggest this relationship also exists within individual leaves.

PMID- 22146059
TI  - Welcome to medical gas research.

PMID- 22146060
TI  - A specific multi-nutrient formulation enhances M1 muscarinic acetylcholine
      receptor responses in vitro.
AB  - Recent evidence indicates that supplementation with a specific combination of
      nutrients may affect cell membrane synthesis and composition. To investigate
      whether such nutrients may also modify the physical properties of membranes, and
      affect membrane-bound processes involved in signal transduction pathways, we
      studied the effects of nutrient supplementation on G protein-coupled receptor
      activation in vitro. In particular, we investigated muscarinic receptors, which
      are important for the progression of memory deterioration and pathology of
      Alzheimer's disease. Nerve growth factor differentiated pheochromocytoma cells
      that were supplemented with specific combinations of nutrients showed enhanced
      responses to muscarinic receptor agonists in a membrane potential assay. The
      largest effects were obtained with a combination of nutrients known as FortasynTM
      Connect, comprising docosahexaenoic acid, eicosapentaenoic acid, uridine
      monophosphate as a uridine source, choline, vitamin B6, vitamin B12, folic acid,
      phospholipids, vitamin C, vitamin E, and selenium. In subsequent experiments, it
      was shown that the effects of supplementation could not be attributed to single
      nutrients. In addition, it was shown that the agonist-induced response and the
      supplement-induced enhancement of the response were blocked with the muscarinic
      receptor antagonists atropine, telenzepine, and AF-DX 384. In order to determine
      whether the effects of FortasynTM Connect supplementation were receptor subtype
      specific, we investigated binding properties and activation of human muscarinic
      M1, M2 and M4 receptors in stably transfected Chinese hamster ovary cells after
      supplementation. Multi-nutrient supplementation did not change M1 receptor
      density in plasma membranes. However, M1 receptor-mediated G protein activation
      was significantly enhanced. In contrast, supplementation of M2- or M4-expressing
      cells did not affect receptor signaling. Taken together, these results indicate
      that a specific combination of nutrients acts synergistically in enhancing
      muscarinic M1 receptor responses, probably by facilitating receptor-mediated G
      protein activation.

PMID- 22146061
TI  - Causative significance of bladder blood flow in lower urinary tract symptoms.
AB  - The association between metabolic syndrome and lower urinary tract symptoms has
      been attracting enormous interest and attention. This enthusiasm is based on the
      presence of many common risk factors being involved in both metabolic syndrome
      and lower urinary tract symptoms, as shown by various epidemiological studies.
      Metabolic syndrome and lower urinary tract symptoms have many pathophysiological
      features in common, particularly overactive bladder. Herein, we analyze the
      pathophysiological relationship between metabolic syndrome and lower urinary
      tract symptoms with a special emphasis on bladder blood flow. We also propose a
      new treatment strategy for treating lower urinary tract symptoms from the
      viewpoint of bladder blood flow.

PMID- 22146062
TI  - Delineating Europe's cultural regions: population structure and surname
      clustering.
AB  - Surnames (family names) show distinctive geographical patterning and in many
      disciplines remain an underutilized source of information about population
      origins, migration and identity. This paper investigates the geographical
      structure of surnames, using a unique individual level database assembled from
      registers and telephone directories from 16 European countries. We develop a
      novel combination of methods for exhaustively analyzing this multinational data
      set, based upon the Lasker Distance, consensus clustering and multidimensional
      scaling. Our analysis is both data rich and computationally intensive, entailing
      as it does the aggregation, clustering and mapping of 8 million surnames
      collected from 152 million individuals. The resulting regionalization has
      applications in developing our understanding of the social and cultural
      complexion of Europe, and offers potential insights into the long and short-term
      dynamics of migration and residential mobility. The research also contributes a
      range of methodological insights for future studies concerning spatial clustering
      of surnames and population data more widely. In short, this paper further
      demonstrates the value of surnames in multinational population studies and also
      the increasing sophistication of techniques available to analyze them.

PMID- 22146063
TI  - Historical sketch of Slovak Haban (Hutterite) population based on autosomal STR
      analysis.
AB  - According to the Hutterite chronicles, the Habans arrived from Austrian Tyrol,
      Switzerland, and northernmost Italy and stayed in four regions of Slovakia
      (Sobotiste, Vel'ke Levare, Moravsky Svaty Jan, Trencin). There are some
      communities in western Slovakia that retained their Haban cultural identity and
      still identify themselves as descendents of the Hutterite population with their
      own specific customs. Slovak Habans are typical founder population with
      significant social isolation for which high degree of inbreeding is typical.
      Present study investigated STR polymorphisms as a powerful genetic tool for
      population genetic studies. The aim was to perform a comparative, population
      genetic study based on 15 STR loci widely used in forensic genetics, of the Haban
      population, the Slovak majority population and the population of Tyrol. We
      analyzed allele frequencies and other statistical parameters in three selected
      populations in order to identify groups of specific ethnic origin and establish
      their genetic relationship. The data set included 110 unrelated Habans and 201
      unrelated individuals from the Slovak majority population, as well as allelic
      frequencies for the population of Austrian Tyrol available in the literature.
      Population pairwise FST values used as a short term genetic distance between
      populations showed significant differentiation between the Habans and both
      reference populations (FST=0.0025 and 0.0042 for comparison with the Slovaks and
      Austrians, respectively; p<10(-3)). The Slovak Hutterites were demonstrated to be
      genetically distinct and more closely related to their geographic neighbors than
      to their historical ancestral population, which may be at least partially
      explained by gene flow between neighboring Haban and Slovak populations.

PMID- 22146064
TI  - Human Alu insertion polymorphisms in North African populations.
AB  - Several features make Alu insertions a powerful tool used in population genetic
      studies: the polymorphic nature of many Alu insertions, the stability of an Alu
      insertion event and, furthermore, the ancestral state of an Alu insertion is
      known to be the absence of the Alu element at a particular locus and the presence
      of an Alu insertion at the site that forward mutational change. This study
      analyses seven Alu insertion polymorphisms in a sample of 297 individuals from
      the autochthonous population of Tunisia (Thala, Smar, Zarzis, and Bou Salem) and
      Libya with the aim of studying their genetic structure with respect to the
      populations of North Africa, Western, Eastern and Central Europe. The comparative
      analyses carried out using the MDS and AMOVA methods reveal the existence of
      spatial heterogeneity, and identify four population groups. Study populations
      (Libya, Smar, Zarzis, and Bou Salem) are closest to North African populations
      whereas Thala is isolated and is closest to Western European populations. In
      conclusion, Results of the present study support the important role that
      migratory movements have played in the North African gene pool, at least since
      the Neolithic period.

PMID- 22146065
TI  - Afro-derived Amazonian populations: inferring continental ancestry and population
      substructure.
AB  - A panel of Ancestry Informative Markers (AIMs) was used to identify population
      substructure and estimate individual and overall interethnic admixture in 294
      individuals from seven African-derived communities of the Brazilian Amazon. A
      panel of 48 biallelic markers, representing the insertion (IN) or the deletion
      (DEL) of small DNA fragments, was employed for this purpose. Overall interethnic
      admixture estimates showed high miscegenation with other ethnic groups in all
      populations (between 46% and 64%). The proportion of ancestral genes varied
      significantly among individuals of the sample: the contribution of African genes
      varied between 12% and 75%; of European genes between 10% and 73%; and of
      Amerindians genes between 8% and 66%. The obtained data reveal a high
      contribution of Amerindian genes in these communities, unlike in other African
      derived communities of the Northeast and the South of Brazil. In addition, the
      majority of the Amerindian contribution may result from the preferential
      inclusion of indigenous women in the African descent groups. High heterogeneity
      of the proportion of interethnic admixture among analyzed individuals was found
      when the proportion of ancestral genes of each individual of the sample was
      estimated. This heterogeneity is reflected in the fact that four populations can
      be considered as substructured and that the global African descent sample is
      possibly formed by two subpopulations.

PMID- 22146066
TI  - Interview with Sarah Tishkoff: perspectives for genetic research in African
      populations. Interview by Giovanni Destro-Bisol.

PMID- 22146068
TI  - Improved brain MRI indices in the acute brain stem infarct sites treated with
      hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone
      alone. A non-controlled study.
AB  - BACKGROUND: In acute stage of cerebral infarction, MRI indices (rDWI & rADC)
      deteriorate during the first 3-7 days after the ictus and then gradually
      normalize in approximately 10 days (pseudonormalization time), although the
      tissue is already infarcted. Since effective treatments improve these indices
      significantly and in less than the natural pseudonormalization time, a combined
      analysis of these changes provides an opportunity for objective evaluation on the
      effectiveness of various treatments for cerebral infarction. Hydroxyl radicals
      are highly destructive to the tissue and aggravate cerebral infarction. We
      treated brainstem infarction patients in acute stage with hydroxyl radical
      scavengers (Edaravone and hydrogen) by intravenous administration and evaluated
      the effects of the treatment by a serial observation and analysis of these MRI
      indices. The effects of the treatment were evaluated and compared in two groups,
      an Edaravone alone group and a combined group with Edaravone and hydrogen, in
      order to assess beneficial effects of addition of hydrogen. METHODS: The patients
      were divided in Edaravone only group (E group. 26 patients) and combined
      treatment group with Edaravone and hydrogen enriched saline (EH group. 8
      patients). The extent of the initial hump of rDWI, the initial dip of rADC and
      pseudo-normalization time were determined in each patient serially and averages
      of these data were compared in these two groups and also with the natural course
      in the literatures. RESULTS: The initial hump of rDWI reached 2.0 in the E group
      which was better than 2.5 of the natural course but was not as good as 1.5 of the
      EH group. The initial dip of rADC was 0.6 in the E group which was close to the
      natural course but worse than 0.8 of the EH group. Pseudonormalization time of
      rDWI and rADC was 9 days only in EH group but longer in other groups. Addition of
      hydrogen caused no side effects. CONCLUSIONS: Administration of hydroxyl radical
      scavengers in acute stage of brainstem infarction improved MRI indices against
      the natural course. The effects were more obvious and significant in the EH
      group. These findings may imply the need for more frequent daily administration
      of hydroxyl scavenger, or possible additional hydrogen effects on scavenger
      mechanisms.

PMID- 22146069
TI  - Measuring the penetration of ambient ozone into residential buildings.
AB  - Much of human exposure to ambient ozone and ozone reaction byproducts occurs
      inside buildings. However, there are currently no experimental data on the
      ability of ozone to penetrate through building envelopes and into residences.
      This paper presents a method to determine the penetration factor for ozone in
      buildings, and applies it in an unoccupied test house and seven single-family
      residences. The mean (+/-SD) ozone penetration factor was measured as 0.79 +/-
      0.13 in the eight homes using this method, ranging from 0.62 +/- 0.09 to 1.02 +/-
      0.15. An analysis of tests across the homes revealed that ozone penetration was
      significantly higher in homes with more painted wood envelope materials, homes
      with larger air leakage exponents from fan pressurization tests, and older homes.
      The test method utilizes a large calibrated fan to elevate air exchange rates and
      steady-state indoor ozone concentrations to levels that can be accurately
      measured, so there is a potential for overpredicting ozone penetration factors.
      However, evidence suggests that this bias is likely small in most of the homes,
      and, even if a bias exists, the measured ozone penetration factors were lower
      than the usual assumption of unity in seven of the eight tested homes.

PMID- 22146070
TI  - Novel multiplexed genotyping of human papillomavirus using a VeraCode-allele
      specific primer extension method.
AB  - A VeraCode-allele-specific primer extension (ASPE) method was applied to the
      detection and genotyping of human papillomavirus (HPV)-DNA. Oligonucleotide
      primers containing HPV-type-specific L1 sequences were annealed to HPV-DNA
      amplified by PGMY-PCR, followed by ASPE to label the DNA with biotinylated
      nucleotides. The labeled DNA was captured by VeraCode beads through
      hybridization, stained with a streptavidin-conjugated fluorophore, and detected
      by an Illumina BeadXpress(r) reader. By using this system, 16 clinically
      important HPV types (HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66
      and 68) were correctly genotyped in a multiplex format. The VeraCode-ASPE
      genotyping of clinical DNA samples yielded identical results with those obtained
      by validated PGMY-reverse blot hybridization assay, providing a new platform for
      high-throughput genotyping required for HPV epidemiological surveys.

PMID- 22146071
TI  - Aerobic visible-light photoredox radical C-H functionalization: catalytic
      synthesis of 2-substituted benzothiazoles.
AB  - An aerobic visible-light driven photoredox catalytic formation of 2-substituted
      benzothiazoles through radical cyclization of thioanilides has been accomplished.
      The reaction features C-H functionalization and C-S bond formation with no direct
      metal involvement except the sensitizer. The reaction highlights the following:
      (1) visible-light is the reaction driving force; (2) molecular oxygen is the
      terminal oxidant, and (3) water is the only byproduct.

PMID- 22146072
TI  - Recognition of double-stranded RNA by guanidine-modified peptide nucleic acids.
AB  - Double-helical RNA has become an attractive target for molecular recognition
      because many noncoding RNAs play important roles in the control of gene
      expression. Recently, we discovered that short peptide nucleic acids (PNA) bind
      strongly and sequence selectively to a homopurine tract of double-helical RNA via
      formation of a triple helix. Herein, we tested if the molecular recognition of
      RNA could be enhanced by alpha-guanidine modification of PNA. Our study was
      motivated by the discovery of Ly and co-workers that the guanidine modification
      greatly enhances the cellular delivery of PNA. Isothermal titration calorimetry
      showed that the guanidine-modified PNA (GPNA) had reduced affinity and sequence
      selectivity for triple-helical recognition of RNA. The data suggested that in
      contrast to unmodified PNA, which formed a 1:1 PNA-RNA triple helix, GPNA
      preferred a 2:1 GPNA-RNA triplex invasion complex. Nevertheless, promising
      results were obtained for recognition of biologically relevant double-helical
      RNA. Consistent with enhanced strand invasion ability, GPNA derived from d
      arginine recognized the transactivation response element of HIV-1 with high
      affinity and sequence selectivity, presumably via Watson-Crick duplex formation.
      On the other hand, strong and sequence selective triple helices were formed by
      unmodified and nucelobase-modified PNA and the purine-rich strand of the
      bacterial A-site. These results suggest that appropriate chemical modifications
      of PNA may enhance molecular recognition of complex noncoding RNAs.

PMID- 22146073
TI  - Assessing forest products usage and local residents' perception of environmental
      changes in peri-urban and rural mangroves of Cameroon, Central Africa.
AB  - BACKGROUND: Deforestation is one of the most ubiquitous forms of land degradation
      worldwide. Although remote sensing and aerial photographs can supply valuable
      information on land/use cover changes, they may not regularly be available for
      some tropical coasts (e.g., Cameroon estuary) where cloud cover is frequent. With
      respect to mangroves, researchers are now employing local knowledge as an
      alternative means of understanding forest disturbances. This paper was primarily
      aimed at assessing the mangrove forest products usage, along with the local
      people's perceptions on environmental changes, between Littoral (Cameroon
      estuary) and Southern (mouth of the Nyong River and Mpalla village) regions of
      Cameroon. METHODS: The data from both locations were obtained through conducting
      household interviews and field observations. RESULTS: In the Cameroon estuary
      (Littoral region), 69.23% of respondents (mostly elders) could distinguish two to
      four mangrove plants, whereas the informants (65.45%) in the mouth of the Nyong
      River and Mpalla village (mostly young people interviewed from the Southern
      region) are familiar with only one or two commonly found mangroves. Also, more
      respondents from the Cameroon estuary are depending on mangroves for fuelwood
      (Rhizophora spp.) and housing (Rhizophora spp., Avicennia germinans (L.) Stearn
      and Nypa fruticans (Thumb.) Wurmb.) purposes, in contrast to Nyong River mouth
      and Mpalla village. Although local people perceived wood extraction as a greater
      disruptive factor, there are several causes for mangrove depletion in the
      Cameroon estuary. Among others, over-harvesting, clear-felled corridors, sand
      extraction and housing were found important. Furthermore, a decline in mangrove
      fauna composition (in terms of fishery products) was recorded in the Littoral as
      well as Southern regions. However, the causes of such perceived negative changes
      were not similar in both cases. CONCLUSIONS: Findings of this study highlight the
      need to improve sustainable management of the mangrove ecosystems through
      afforestation (in large impacted areas), selective removal of senescent tree
      stems and branches (in little damage stands), regulating sand extraction and
      housing activities, and creating awareness and law enforcement.

PMID- 22146075
TI  - Diagnosing adult attention-deficit hyperactivity disorder: the importance of
      establishing daily life contexts for symptoms and impairments.
AB  - This integrative literature review examines the complexity of diagnosing
      attention-deficit hyperactivity disorder (ADHD) in adults with regard to the
      presence of symptoms and comorbidities common to mood, anxiety and other
      disorders. In adults, symptoms are often masked by the patient's learned
      compensatory mechanisms. Misdiagnosis, and subsequent treatment, can moderate
      common symptoms without relieving the core difficulties of inattention,
      hyperactivity and impulsivity. This review was conducted to identify methods of
      improving diagnostic clarity. The literature reveals the importance of evaluating
      both retrospective and current symptoms and impairments in the context of the
      individual's life. Careful, nuanced assessment of the relationship between
      symptom expression and impairment in daily living offers diagnostic clarity.
      Symptoms common to multiple disorders will be distinguished by illuminating the
      context in which they arise and are experienced. Well-supported assessments,
      sensitive to the context in which symptoms and impairments present, will result
      in greater diagnostic accuracy, better treatment outcomes and enhanced quality of
      life. Accurate diagnoses will contribute to the understanding of adult ADHD and
      remind both clinicians and the public that this disorder is often present in
      adults as well as children.

PMID- 22146074
TI  - Utilizing experimental data for reducing ensemble size in flexible-protein
      docking.
AB  - Efficient and sufficient incorporation of protein flexibility into docking is
      still a challenging task. Docking to an ensemble of protein structures has proven
      its utility for docking, but using a large ensemble of structures can reduce the
      efficiency of docking and can increase the number of false positives in virtual
      screening. In this paper, we describe the application of our new methodology,
      Limoc, to generate an ensemble of holo-like protein structures in combination
      with the relaxed complex scheme (RCS), to virtual screening. We describe
      different schemes to reduce the ensemble of protein structures to increase
      efficiency and enrichment quality. Utilizing experimental knowledge about actives
      for a target protein allows the reduction of ensemble members to a minimum of
      three protein structures, increasing enrichment quality and efficiency
      simultaneously.

PMID- 22146076
TI  - The impact of dihydrogen phosphate anions on the excited-state proton transfer of
      harmane. Effect of beta-cyclodextrin on these photoreactions.
AB  - Photoinduced proton transfer reactions of harmane (1-methyl-9H-pyrido[3,4
      b]indole) (HAR) in the presence of a proton donor/acceptor such as dihydrogen
      phosphate anions in aqueous solution have been studied by stationary and time
      resolved fluorescence spectroscopy. The presence of high amounts of dihydrogen
      phosphate ions modifies the acid/base properties of this alkaloid. Thus, by
      keeping the pH constant at pH 8.8 and by increasing the amount of NaH(2)PO(4) in
      the solution, it is possible to reproduce the same spectral profiles as those
      obtained in high alkaline solutions (pH >12) in the absence of NaH(2)PO(4). Under
      these conditions, a new fluorescence profile appears at around 520 nm. This
      result could be related to the results of a recent investigation which suggests
      that a high intake of phosphates may promote skin tumorigenesis. The presence of
      beta-cyclodextrin (beta-CD) avoids the proton transfer reactions in this alkaloid
      by means the formation of an inclusion complex between beta-CD and HAR. The
      formation of this complex originates a remarkable enhancement of the emission
      intensity from the neutral form in contrast to the cationic and zwitterionic
      forms. A new lifetime was obtained at 360 nm (2.5 ns), which was associated with
      the emission of this inclusion complex. At this wavelength, the fluorescence
      intensity decay of HAR can be described by a linear combination of two
      exponentials. From the ratio between the pre-exponential factors, we have
      obtained a value of K = 501 M for the equilibrium of formation of this complex.

PMID- 22146077
TI  - One fungus, one name promotes progressive plant pathology.
AB  - The robust and reliable identification of fungi underpins virtually every element
      of plant pathology, from disease diagnosis to studies of biology,
      management/control, quarantine and, even more recently, comparative genomics.
      Most plant diseases are caused by fungi, typically pleomorphic organisms, for
      which the taxonomy and, in particular, a dual nomenclature system have frustrated
      and confused practitioners of plant pathology. The emergence of DNA sequencing
      has revealed cryptic taxa and revolutionized our understanding of relationships
      in the fungi. The impacts on plant pathology at every level are already immense
      and will continue to grow rapidly as new DNA sequencing technologies continue to
      emerge. DNA sequence comparisons, used to resolve a dual nomenclature problem for
      the first time only 19 years ago, have made it possible to approach a natural
      classification for the fungi and to abandon the confusing dual nomenclature
      system. The journey to a one fungus, one name taxonomic reality has been long and
      arduous, but its time has come. This will inevitably have a positive impact on
      plant pathology, plant pathologists and future students of this hugely important
      discipline on which the world depends for food security and plant health in
      general. This contemporary review highlights the problems of a dual nomenclature,
      especially its impact on plant pathogenic fungi, and charts the road to a one
      fungus, one name system that is rapidly drawing near.

PMID- 22146078
TI  - Docking, CoMFA and CoMSIA studies of a series of sulfonamides derivatives as
      carbonic anhydrase I inhibitors.
AB  - 3D-QSAR methods, CoMFA region focusing (CoMFA-RF) and CoMSIA along with docking
      studies carried out for investigating 32 carbonic anhydrase I inhibitors. These
      inhibitors have been studied for the development of antiglaucoma, antitumor,
      antiobesity or anticonvulsant drugs. Docking analysis by GOLD provide
      conformations which have been realigned in CoMFA and CoMSIA models. Training set
      for the CoMFA-RF and CoMSIA models using 24 docked conformations gives q(2)(Loo)
      values of 0.615 and 0.637 and r(2)(nv) values of 0.701 and 0.713, respectively.
      The results of CoMFA-RF and CoMSIA with and without docked conformations were
      compared. The ability of prediction and robustness of the models were evaluated
      by test set, cross validation (leave-one-out and leave-ten-out), bootstrapping,
      and progressive scrambling approaches. The all-orientation search (AOS) was used
      to achieve the best orientation to minimize the effect of initial orientation of
      the structures. The docking results confirmed CoMFA and CoMSIA contour maps.

PMID- 22146079
TI  - Small molecule inhibitors of anthrax toxin-induced cytotoxicity targeted against
      protective antigen.
AB  - Two molecular scaffolds were designed using the CAVEAT molecular design package
      to inhibit the oligomerization of protective antigen (PA(63) ), a key protein
      component of anthrax toxin. The inhibitors were designed to prevent
      heptamerization of PA(63)  by mimicking key residues of PA(63)  needed for the
      intermolecular interactions that stabilize the heptamer. Using the scaffolds
      identified by CAVEAT, seven candidate inhibitors were synthesized and tested for
      their ability to inhibit anthrax toxin-induced cytotoxicity, with three of the
      agents demonstrating modest inhibition in murine J774A.1 macrophage cells.

PMID- 22146080
TI  - Long-term results of giant hiatal hernia mesh repair and antireflux laparoscopic
      surgery for gastroesophageal reflux disease.
AB  - BACKGROUND: The application of mesh-reinforced hiatal closure has resulted in a
      significant reduction in recurrence rates. The most debated issue is the risk of
      complications related to the use of the prosthesis, which are thought to be the
      cause of higher dysphagia. PATIENTS AND METHODS: From January 2004 to December
      2007, 198 consecutive patients underwent laparoscopic fundoplication for
      gastroesophageal reflux disease (GERD) with or without hiatal hernia. Fifty
      patients (25.3%) presented a giant hiatal hernia, defined as a hiatal defect over
      5 cm. These 50 patients underwent primary simple suture of the crura and
      additional reinforcement with a Crurasoft mesh (Bard). Hiatal hernia or GERD
      symptoms recurrence, dysphagia, and mesh-related complications were investigated.
      RESULTS: Of the 50 patients undergoing mesh repair, there were 32 women and 18
      men with a mean age of 63.2 years. Conversion rate was 2%. Intraoperative
      complications rate was 6%, all of them laparoscopically managed. Postoperative
      complications occurred in 1 patient (2%). Mortality rate was 2%. Median
      postoperative stay was 3 days. Median follow-up was 62 months. Two percent of the
      patients presented wrap migration, and 4% presented dysphagia. Six percent of
      cases presented recurrence of GERD manifestations. There have been no
      complications related to the use of the mesh. CONCLUSIONS: Laparoscopic
      antireflux surgery with a prosthetic mesh in cases of giant hiatal hernia is an
      effective and safe procedure, reducing the rate of postoperative hernia
      recurrence during long-term follow-up. The incidence of mesh-related
      complications is very low.

PMID- 22146082
TI  - The 2011 Medical Molecular Hydrogen Symposium: An inaugural symposium of the
      journal Medical Gas Research.
AB  - This report summarizes a brief description/history of the Hydrogen Research
      Meetings as well as key presentations/oral abstracts delivered in the most recent
      symposium. Additionally, we introduced 38 diseases and physiological states for
      which hydrogen exhibits beneficial effects.

PMID- 22146083
TI  - Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a
      metabolic syndrome rat model.
AB  - BACKGROUND: Hydrogen (H2), a potent free radical scavenger, selectively reduces
      the hydroxyl radical, which is the most cytotoxic of the reactive oxygen species
      (ROS). An increase in oxygen free radicals induces oxidative stress, which is
      known to be involved in the development of metabolic syndrome. Therefore, we
      investigated whether hydrogen-rich water (HRW) affects metabolic abnormalities in
      the metabolic syndrome rat model, SHR.Cg-Leprcp/NDmcr (SHR-cp). METHODS: Male SHR
      cp rats (5 weeks old) were divided into 2 groups: an HRW group was given oral HRW
      for 16 weeks, and a control group was given distilled water. At the end of the
      experiment, each rat was placed in a metabolic cage for 24 h, fasted for 12 h,
      and anesthetized; the blood and kidneys were then collected. RESULTS: Sixteen
      weeks after HRW administration, the water intake and urine flow measured in the
      metabolic cages were significantly higher in the HRW group than in the control
      group. The urinary ratio of albumin to creatinine was significantly lower and
      creatinine clearance was higher in the HRW group than in the control group. After
      the 12-h fast, plasma urea nitrogen and creatinine in the HRW group were
      significantly lower than in the control group. The plasma total antioxidant
      capacity was significantly higher in the HRW group than in the control group. The
      glomerulosclerosis score for the HRW group was significantly lower than in the
      control group, and a significantly positive correlation was observed between this
      score and plasma urea nitrogen levels. CONCLUSION: The present findings suggest
      that HRW conferred significant benefits against abnormalities in the metabolic
      syndrome model rats, at least by preventing and ameliorating glomerulosclerosis
      and creatinine clearance.

PMID- 22146084
TI  - The Female Sexual Function Index: translation and validation of an Iranian
      version.
AB  - INTRODUCTION: Female sexual dysfunction (FSD) is a prevalent problem in the
      female population in Iran. A subjective assessment instrument that allows cross
      cultural comparison of FSD is urgently needed. AIM: The aims of the study were to
      translate, validate, and enhance cross-cultural comparability of an Iranian
      version (IV) of the Female Sexual Function Index (FSFI)-the IV-FSFI. METHODS: A
      total of 448 women (19-54 years, mean 29.7, standard deviation 7.3) from five
      different Iranian outpatient obstetrics and gynecology clinics were eligible for
      this study. The IV-FSFI was developed through forward and backward translation,
      revision by a research team, and a subsequent pilot study. After an interview for
      clinical diagnosis of FSD based on the Diagnostic and Statistical Manual of
      Mental Disorders, all participants completed the IV-FSFI for the validation
      study. Three hundred sixty-two women completed the IV-FSFI again, 4 weeks after
      the first visit. MAIN OUTCOME MEASURES: Test-retest reliability was determined by
      Pearson's product-moment correlations. Reliability was tested using Cronbach's
      alpha coefficient. Construct validity was evaluated by principal component
      analysis using varimax rotation and by subsequent confirmatory factor analysis
      (CFA). Discriminant validity was assessed with between-groups analysis of
      variance. RESULTS: The overall test-retest reliability coefficients were high for
      each domain of the IV-FSFI (r ranging from 0.73 to 0.86) and the internal
      consistencies within the acceptable range (alpha from 0.72 to 0.90). Principal
      component analysis with varimax rotation revealed a best fitting five-factor
      structure similar to the original FSFI (chi(2) = 2.1, degree of freedom = 17, P <
      0.001). CFA confirmed the underlying domain structure, supporting the factorial
      validity of the IV-FSFI. CONCLUSIONS: In conclusion, the newly developed IV-FSFI
      has demonstrated to be a reliable and valid instrument with good psychometric
      properties that allows a quick and accurate preliminary screening of women with
      unknown sexual health status in clinics and other medical settings.

PMID- 22146085
TI  - Influence of depth and time on diversity of free-living microbial community in
      the variably saturated zone of a granitic aquifer.
AB  - We investigated the temporal and vertical changes in the microbial communities
      related to hydrological variations an aquifer (Brittany, France). Five water
      samplings were carried out, spanning three hydrological cycles in the variably
      and the permanently saturated zones. Seasonal variations in the major anion
      concentrations (NO3 -, SO4 2- and Cl(-) ) indicated that different physical
      processes occurred during the recharge process in the two zones. The variably
      saturated zone is mainly dominated by diffusion and advection processes from the
      soil, whereas the permanently saturated zone is controlled by moderate advective
      transfer from the variably saturated zone. Bacterial diversity was investigated
      by flow cytometry, 16S rRNA and narG genes analyses. Part of this diversity was
      new in that 6 of the 27 16S rRNA gene sequence phylotypes were unknown even at
      the class or phylum level. The narG gene analysis did not reveal any clear
      variation in time or depth within the nitrate reducers' community. In contrast,
      16S rRNA gene analyses showed modifications of community composition that could
      be related to the hydrologic and chemical contrast between the two zones. It was
      concluded that the physical processes of water transfer could influence bacterial
      diversity at the soil-aquifer interface.

PMID- 22146086
TI  - Health and nutritional status of Wistar rats following subchronic exposure to
      CV127 soybeans.
AB  - This subchronic duration feeding study evaluated the nutritional and health
      status of rats fed diets containing CV127 at incorporation levels of 11% and 33%.
      For control comparisons, rats were also exposed to similar incorporation levels
      of the near isogenic conventional soybean variety (Conquista) and two other
      conventional soybean varieties (Monsoy, Coodetec). In spite of phenotypic
      differences among these four soybean varieties, there were no quantitative
      differences in their respective proximate and other compositional properties,
      including proteins, amino acids, antinutrients and nutritional cofactors. All
      diets were prepared by blending the respective processed soybean meal with ground
      Kliba maintenance meal at high (33%) and low (11%) incorporation levels, and the
      blended diets were fed to Wistar rats for about 91 days. Although there were some
      isolated parameters indicating statistically significant changes, these lacked
      consistency and a plausible mechanism and were thus assessed to be incidental.
      The totality of results demonstrate that CV127 soybeans are similar with respect
      to their nutritional value and systemic effects as its near isogenic conventional
      counterpart, as well as other conventional soybean varieties. Hence, introduction
      of AHAS gene into soybeans does not substantially alter its compositional
      properties, nor adversely affect its nutritional or safety status to mammals.

PMID- 22146087
TI  - A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity
      induced hypothalamic inflammation.
AB  - Obesity can be associated with systemic low-grade inflammation that contributes
      to obesity-related metabolic disorders. Recent studies raise the possibility that
      hypothalamic inflammation contributes to the pathogenesis of diet-induced obesity
      (DIO), while another study reported that obesity decreases the expression of pro
      inflammatory cytokines in spleen. The following study examines the hypothesis
      that obesity suppresses the splenic synthesis of the anti-inflammatory cytokine,
      interleukin (IL)-10, thereby resulting in chronic hypothalamic inflammation. The
      results showed that due to oxidative stress or apoptosis, the synthesis of
      splenic IL-10 was decreased in DIO when compared with non-obesity rats.
      Splenectomy (SPX) accelerated DIO-induced inflammatory responses in the
      hypothalamus. Interestingly, SPX suppressed the DIO-induced increases in food
      intake and body weight and led to a hypothalamic pro-inflammatory state that was
      similar to that produced by DIO, indicating that hypothalamic inflammation exerts
      a dual effect on energy metabolism. These SPX-induced changes were inhibited by
      the systemic administration of IL-10. Moreover, SPX had no effect on hypothalamic
      inflammatory responses in IL-10-deficient mice. These data suggest that spleen
      derived IL-10 plays an important role in the prevention of hypothalamic
      inflammation and may be a therapeutic target for the treatment of obesity and
      hypothalamic inflammation.

PMID- 22146088
TI  - An acquired CSF3R mutation in an adult chronic idiopathic neutropenia patient who
      developed acute myeloid leukaemia.

PMID- 22146089
TI  - Methylenetetrahydrofolate reductase C677T gene polymorphism and coronary artery
      disease in a Chinese Han population: a meta-analysis.
AB  - Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism has been
      suggested to be associated with increased coronary artery disease (CAD) risk. To
      explore the relationship between MTHFR C677T gene polymorphism and CAD in the
      Chinese Han population, a meta-analysis was performed. Fourteen separate studies
      were included and 2981 subjects were involved in the current meta-analysis. The
      pooled odds ratio (OR) between CAD size to CAD size and control size (CAD/CAD +
      control) and the corresponding 95% confidence interval (95% CI) between the CC
      and TT genotype groups were estimated by a random-effects model. Meta-regression
      was performed to explore the heterogeneity source. The CAD/CAD + control values
      were 0.45 for the CC genotype group and 0.62 for the TT genotype group. The
      pooled OR for the CAD/CAD + control between the CC and TT genotype groups was
      0.55 (95% CI, 0.37-0.83; P(heterogeneity) = .0004, I(2) = 64.7%). These results
      indicated that MTHFR C677T gene polymorphism and CAD were significantly
      associated (P = .005) in the Chinese Han population. Publication year was
      detected as the main heterogeneity source. In a stratified analysis by
      publication year, the pooled OR was 0.76 (95% CI, 0.37-1.57; P(heterogeneity) =
      .0002; I(2) = 79.6%) in subgroup 1 (publication years 1999-2004). No significant
      association between gene polymorphism and CAD was found in this subgroup (P =
      .46). In subgroup 2 (publication years 2005-2011), the pooled OR was 0.39 (95%
      CI, 0.28-0.55; P(heterogeneity) = .53; I(2) = 0); and the association between
      gene polymorphism and CAD was significant (P < .00001). In the Chinese Han
      population, the TT genotype for the MTHFR C677T gene appeared to be associated
      with increased CAD risk.

PMID- 22146081
TI  - Redox regulation of mitochondrial function.
AB  - Redox-dependent processes influence most cellular functions, such as
      differentiation, proliferation, and apoptosis. Mitochondria are at the center of
      these processes, as mitochondria both generate reactive oxygen species (ROS) that
      drive redox-sensitive events and respond to ROS-mediated changes in the cellular
      redox state. In this review, we examine the regulation of cellular ROS, their
      modes of production and removal, and the redox-sensitive targets that are
      modified by their flux. In particular, we focus on the actions of redox-sensitive
      targets that alter mitochondrial function and the role of these redox
      modifications on metabolism, mitochondrial biogenesis, receptor-mediated
      signaling, and apoptotic pathways. We also consider the role of mitochondria in
      modulating these pathways, and discuss how redox-dependent events may contribute
      to pathobiology by altering mitochondrial function.

PMID- 22146091
TI  - Metabolic consequences of stress during childhood and adolescence.
AB  - Stress, that is, the state of threatened or perceived as threatened homeostasis,
      is associated with activation of the stress system, mainly comprised by the
      hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems.
      The stress system normally functions in a circadian manner and interacts with
      other systems to regulate a variety of behavioral, endocrine, metabolic, immune,
      and cardiovascular functions. However, the experience of acute intense physical
      or emotional stress, as well as of chronic stress, may lead to the development of
      or may exacerbate several psychologic and somatic conditions, including anxiety
      disorders, depression, obesity, and the metabolic syndrome. In chronically
      stressed individuals, both behavioral and neuroendocrine mechanisms promote
      obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with
      dysregulation of the stress system and increased secretion of cortisol,
      catecholamines, and interleukin-6, with concurrently elevated insulin
      concentrations, lead to development of central obesity, insulin resistance, and
      the metabolic syndrome. Fetal life, childhood, and adolescence are particularly
      vulnerable periods of life to the effects of intense acute or chronic stress.
      Similarly, these life stages are crucial for the later development of behavioral,
      metabolic, and immune abnormalities. Developing brain structures and functions
      related to stress regulation, such as the amygdala, the hippocampus, and the
      mesocorticolimbic system, are more vulnerable to the effects of stress compared
      with mature structures in adults. Moreover, chronic alterations in cortisol
      secretion in children may affect the timing of puberty, final stature, and body
      composition, as well as cause early-onset obesity, metabolic syndrome, and type 2
      diabetes mellitus. The understanding of stress mechanisms leading to metabolic
      abnormalities in early life may lead to more effective prevention and
      intervention strategies of obesity-related health problems.

PMID- 22146090
TI  - Leisure time and occupational physical activity in relation to obesity and
      insulin resistance: a population-based study from the Skaraborg Project in
      Sweden.
AB  - The objective was to study obesity and insulin resistance in relation to leisure
      time physical activity (LTPA) and occupational physical activity (OPA) in a
      Swedish population, with particular focus on sex differences. Using a cross
      sectional design, waist circumference, body mass index (BMI), glucose/insulin
      metabolism, blood pressure, heart rate, self-reported education, smoking, alcohol
      consumption, LTPA, and OPA were assessed in 1745 men and women (30-74 years)
      randomly chosen from 2 municipalities in southwestern Sweden. In both men and
      women, LTPA was inversely associated with BMI, waist circumference, and the
      homeostasis model assessment of insulin resistance (HOMA-IR), respectively. These
      associations remained statistically significant after adjustments for age, OPA,
      education, alcohol consumption, smoking, and study area, and also for BMI in the
      analyses concerning waist circumference and HOMA-IR. A statistically significant
      interaction term (P = .030), adjusted for multiple confounders, revealed a
      stronger association between LTPA and HOMA-IR in women compared with men.
      Occupational physical activity was positively associated with BMI (P < .001),
      waist circumference (P < .001), and HOMA-IR (P = .001), however, only in women.
      These associations remained when adjusting for multiple confounders. The sex
      differences were confirmed by statistically significant interaction terms between
      sex and OPA in association with BMI, waist circumference, and HOMA-IR,
      respectively. The observed sex differences regarding the strength of the
      association between LTPA and insulin resistance, and the positive association
      between OPA and obesity and insulin resistance found solely in women, warrant
      further investigation. Although exploration of the metabolic effects of OPA
      appears to be needed, thorough measurement of potential confounders is also vital
      to understand contextual effects.

PMID- 22146092
TI  - In vivo nitric oxide synthesis, insulin sensitivity, and asymmetric
      dimethylarginine in obese subjects without and with metabolic syndrome.
AB  - Metabolic syndrome (MetSyn) is associated with impaired endothelial function.
      Here the association between nitric oxide (NO) production and insulin sensitivity
      (Si) in obese subjects with and without MetSyn was evaluated. The relationship
      between NO production and asymmetric dimethylarginine (ADMA) was also explored.
      Seven healthy normal-weight subjects (male/female [M/F], 3/4; age, 27.4 +/- 10.9
      years; body mass index [BMI], 21.9 +/- 2.2 kg/m(2)), 7 obese subjects without
      MetSyn (M/F, 1/6; age, 48.0 +/- 8.0 years; BMI, 34.5 +/- 2.3 kg/m(2)), and 7 with
      MetSyn (M/F, 3/4; age, 48.0 +/- 10.7 years; BMI, 33.4 +/- 2.9 kg/m(2)) were
      recruited. Body composition and cardiometabolic functions (blood pressure,
      glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein,
      ADMA) were measured. A frequent sampling intravenous glucose tolerance test was
      performed to measure Si. A novel stable isotopic method was used to measure in
      vivo rates of NO production. The NO production was lower in obese subjects with
      MetSyn compared with normal-weight subjects and obese subjects without MetSyn.
      Similarly, Si was significantly lower in obesity, both without and with MetSyn,
      compared with the control group. A significant direct association was found
      between NO synthesis and Si (rho = 0.47, P = .03). Circulating levels of ADMA
      were significantly higher in the obese group with MetSyn. A nonsignificant
      negative trend between ADMA and NO synthesis was observed. The association
      between Si and NO production suggests a close mechanistic link between
      endothelial function and insulin signaling. The results may be highly informative
      for the development of controlled longitudinal interventions to improve
      endothelial and metabolic regulation.

PMID- 22146093
TI  - Maternal serum resistin at 11 to 13 weeks' gestation in normal and pathological
      pregnancies.
AB  - The objective was to examine maternal serum levels of resistin at 11 to 13 weeks'
      gestation in normal and pathological pregnancies. Serum resistin, pregnancy
      associated plasma protein A (PAPP-A), and uterine artery pulsatility index (PI)
      at 11 to 13 weeks were measured in 480 singleton pregnancies, including 240 with
      normal outcome, 60 that subsequently developed preeclampsia (PE), 60 that
      developed gestational diabetes mellitus (GDM), 60 that delivered large for
      gestational age (LGA) neonates, and 60 that delivered small for gestational age
      (SGA) neonates. Each value in both the normal and pathological outcome groups was
      expressed as a multiple of the expected normal median (MoM), and the median MoM
      values in the outcome groups were compared. In the PE group, compared with the
      controls, there were an increase in median resistin (1.22 MoM, P = .003) and
      uterine artery PI (1.25 MoM, P < .0001) and a decrease in serum PAPP-A (0.72, P <
      .0001). There was no significant association between serum resistin with either
      uterine artery PI (P = .415) or serum PAPP-A (P = .290). In the SGA, LGA, and GDM
      groups, serum resistin MoM was not significantly different from that of the
      controls (P = .415, P = .702, and P = .549, respectively). In pregnancies that
      develop PE, maternal serum resistin concentration at 11 to 13 weeks is increased
      in a manner not related to altered placental perfusion or function. In
      pregnancies complicated by the development of GDM or delivery of SGA or LGA
      neonates, serum resistin is not significantly altered.

PMID- 22146094
TI  - Less fat reduction per unit weight loss in type 2 diabetic compared with
      nondiabetic obese individuals completing a very-low-calorie diet program.
AB  - The objective was to compare weight loss and change in body composition in obese
      subjects with and without type 2 diabetes mellitus during a very-low-calorie diet
      (VLCD) program. Seventy weight-matched subjects with diabetes or normal fasting
      glucose (controls) participated in a 24-week VLCD study. Primary end points were
      changes in anthropometry, body composition, and fasting plasma insulin and beta
      hydroxybutyrate concentrations. Fifty-one subjects (24 with diabetes) completed
      the study. No difference in weight loss between the 2 groups at 24 weeks was
      found by intention-to-treat analysis. Both groups completing the study per
      protocol had near-identical weight change during the program, with similar weight
      loss at 24 weeks (diabetes: 8.5 +/- 1.3 kg vs control: 9.4 +/- 1.2 kg, P = .64).
      Change in fat mass index correlated with change in body mass index (BMI) in both
      groups (diabetes: r = 0.878, control: r = 0.920, both P < .001); but change in
      fat mass index per unit change in BMI was less in the diabetic group compared
      with controls (0.574 vs 0.905 decrease, P = .003), which persisted after
      adjusting for age, sex, and baseline BMI (P = .008). Insulin concentrations
      remained higher and peak beta-hydroxybutyrate concentrations were lower in the
      diabetic compared with the control group. While following a 24-week VLCD program,
      obese subjects with and without diabetes achieved comparable weight loss; but the
      decrease in adiposity per unit weight loss was attenuated in diabetic subjects.
      Hyperinsulinemia may have inhibited lipolysis in the diabetic group; however,
      further investigation into other factors is needed.

PMID- 22146095
TI  - Prediction of gestational diabetes mellitus at 24 to 28 weeks of gestation by
      using first-trimester insulin sensitivity indices in Asian Indian subjects.
AB  - The aim of the present study was to predict the development of gestational
      diabetes mellitus (GDM) after 24 weeks of gestation by using first-trimester
      insulin indices. A total of 298 nondiabetic pregnant women underwent 3-hour oral
      glucose tolerance test (OGTT) in the first trimester of pregnancy. The
      normoglycemic women underwent second OGTT between 24 and 28 weeks. Insulin
      sensitivity and resistance indices were calculated by using the Matsuda index
      (composite insulin sensitivity from OGTT), quantitative insulin sensitivity check
      index, and homeostasis model assessment for insulin resistance and sensitivity by
      using the results of the first-trimester OGTT. These indices were compared
      between subjects who were diagnosed as having GDM and subjects with normal
      glucose tolerance in the second OGTT. The overall prevalence of GDM was 15.49%
      (24 in the first trimester and 16 between 24 and 28 weeks). First-trimester
      fasting plasma insulin greater than 7.45 MUU/mL was able to predict GDM with
      sensitivity and specificity of 80% and 57.4%, respectively. The negative
      predictive value for this parameter was 0.97. Values of first-trimester composite
      insulin sensitivity from OGTT less than 5.5 had sensitivity and specificity of
      71.4% and 62.5% for the prediction of GDM. First-trimester hyperinsulinemia
      preceded the onset of hyperglycemia between 24 and 28 weeks of gestation and
      would predict the development of GDM with limited sensitivity and specificity.

PMID- 22146096
TI  - A tea/vanadate decoction delivered orally over 14 months to diabetic rats induces
      long-term glycemic stability without organ toxicity.
AB  - Vanadium can induce potent hypoglycemic effects in type 1 and type 2 diabetes
      mellitus animals, but toxic adverse effects have inhibited the translation of
      these findings. Administration of vanadate in a black tea decoction has shown
      impressive hypoglycemic effects without evidence of toxicity in short-term
      studies. The purpose of this study was to investigate the hypoglycemic action and
      the toxic adverse effects of a tea/vanadate (T/V) decoction in diabetic rats over
      a 14-month treatment period. Streptozotocin-induced type 1 diabetes mellitus rats
      were orally gavaged with 40 mg sodium vanadate in a black tea decoction only when
      blood glucose levels were greater than 10 mmol/L. Glycemic status and liver and
      kidney function were monitored over 14 months. All of the diabetic rats in this
      treatment group (n = 25) required treatment with the T/V decoction at the start
      of the study to reduce blood glucose levels to less than 10 mmol/L. Diarrhea was
      uncommon among the T/V-treated animals during the first week of T/V treatment and
      was absent thereafter. There was no evidence of liver or kidney dysfunction or
      injury. From 2 to 6 months, fewer animals required the T/V treatment to maintain
      their blood glucose levels. After 9 months of treatment, none of the diabetic
      animals required any T/V to maintain their blood glucose levels at less than 10
      mmol/L. Oral administration of a T/V decoction provides safe, long-acting
      hypoglycemic effects in type 1 diabetes mellitus rats. The typical glycemic signs
      of diabetes were absent for the last 5 months of the study.

PMID- 22146097
TI  - Effects of resistance exercise and obesity level on ghrelin and cortisol in men.
AB  - Resistance exercise (RE) is increasingly recommended by health organizations as a
      weight management tool. The purpose of this study was to examine the effects of
      an acute high-volume, whole-body RE protocol on the glucoregulatory and ghrelin
      response in sedentary obese and lean men. Five World Health Organization (WHO)
      class 1 obese (body mass index [BMI], 30.00-34.99) (age, 21.6 +/- 2.5 years;
      height, 176.3 +/- 3.7 cm; body mass, 97.8 +/- 8.58 kg; body fat, 34.7% +/-
      2.95%), 5 WHO 2 (BMI, 35-39.99)/WHO 3 (BMI, >=40) obese (age, 20.0 +/- 1.4 years;
      height, 177.7 +/- 5.15 cm; body mass, 120.8 +/- 10.49 kg; body fat, 40.5% +/-
      5.82 %), and 9 lean men (age, 20.1 +/- 2.1 years; height, 177.8 +/- 8.7 cm; body
      mass, 71.7 +/- 5.8 kg; body fat, 14.7% +/- 3.54 %) completed an acute RE testing
      protocol (6 exercises, 3 sets of 10 repetitions at 85%-95% 10-repetition maximum
      with 120- and 90-second rest periods); and blood samples were collected pre-, mid
      , and immediately postexercise and during recovery (+50, +70, and +110).
      Resistance exercise produced differences over time in cortisol, insulin, and
      glucose. Group differences were observed for ghrelin, with the WHO class 2/3
      group having significantly greater ghrelin levels than the lean group (d = 0.28,
      P = .009) and the WHO class 1 group (d = 0.39, P = .002). Higher ghrelin was
      significantly associated with lower cortisol only in obese individuals. In
      addition, higher growth hormone was associated with lower ghrelin in lean
      individuals. Results suggest that glucoregulatory homeostasis is altered with
      increasing levels of obesity and that these alterations may mediate the response
      of cortisol and ghrelin in response to RE.

PMID- 22146098
TI  - Metastatic clear cell renal cell carcinoma to the adrenal gland without an
      identifiable primary tumor.

PMID- 22146100
TI  - [Management of analgesics in cancer patients with renal impairment].
AB  - Pain is frequent in cancer patients. To date, there is a consequent therapeutic
      arsenal so to manage pain; the different treatment strategies are the subject of
      various recommendations. Patients with cancer also frequently suffer from renal
      insufficiency, and this comorbidity may disrupt or jeopardize the analgesic
      strategy by changing the risk-benefit ratio of treatment options. This article
      provides recommendations for the use of drugs used for pain treatment after
      pointing out: 1) etiological and pathophysiological elements of pain; 2)
      therapeutic strategies for pain management; 3) data regarding renal failure in
      cancer and; 4) a point on drugs pharmacokinetics.

PMID- 22146099
TI  - M2 macrophages exhibit higher sensitivity to oxLDL-induced lipotoxicity than
      other monocyte/macrophage subtypes.
AB  - BACKGROUND: In obesity, phenotypic switches occur in macrophage populations such
      that the predominantly M2-polarised anti-inflammatory state seen in lean
      individuals changes to a predominantly M1-polarised pro-inflammatory state in
      those who are obese. However, the mechanisms by which these phenotypic shifts
      occur have not yet been fully elucidated. RESULTS: The effects of oxLDL (1-40
      MUg/ml; 24 h) on several parameters relevant to the Unfolded Protein Response
      (UPR)-mediated lipotoxic effects of oxLDL (disruption of ER Ca2+ handling;
      activation of the UPR transcription factor XBP-1; upregulation of the UPR target
      genes BiP and CHOP; apoptosis; cell viability) were investigated in human primary
      monocyte-derived macrophages, and also in monocyte-macrophages derived from the
      THP-1 monocytic cell line. A consistent pattern was observed: M2-polarised
      macrophages were more sensitive to the lipotoxic effects of oxLDL than either non
      polarised macrophages or non-differentiated monocytic cells. Specifically, M2
      polarised macrophages were the only cell type to undergo significantly increased
      apoptosis (Primary cells: 1.23 +/- 0.01 basal; THP-1-derived: 1.97 +/- 0.12
      basal; P < 0.05 in both cases) and decreased cell viability (Primary cells: 0.79
      +/- 0.04 basal; THP-1-derived: 0.67 +/- 0.02 basal; P < 0.05 in both cases) when
      exposed to oxLDL levels similar to those seen in overweight individuals (ie. 1
      MUg/ml). CONCLUSIONS: We propose that the enhanced susceptibility of M2-polarised
      macrophages to lipotoxicity seen in the present in vitro study could, over time,
      contribute to the phenotypic shift seen in obese individuals in vivo. This is
      because a higher degree of oxLDL-induced lipotoxic cell death within M2
      macrophages could contribute to a decrease in numbers of M2 cells, and thus a
      relative increase in proportion of non-M2 cells, within macrophage populations.
      Given the pro-inflammatory characteristics of a predominantly M1-polarised state,
      the data presented here may constitute a useful contribution to our understanding
      of the origin of the pro-inflammatory nature of obesity, and of the pathogenesis
      of obesity-associated inflammatory disorders such as Type 2 diabetes and
      atherosclerosis.

PMID- 22146101
TI  - Variation in the oxytocin receptor gene influences neurocardiac reactivity to
      social stress and HPA function: a population based study.
AB  - Oxytocin (OT) is a nonapeptide neurohormone that is involved in a broad array of
      physiological and behavioral processes related to health including hypothalamic
      pituitary-adrenal (HPA) axis functioning, autonomic nervous system (ANS) activity
      and social behaviors. The present study sought to explore the influence of
      genetic variation in the oxytocin receptor (SNP; rs53576) on autonomic and
      neurohormonal functioning across both resting and psychological stress conditions
      in a population based sample of older adults. Results revealed that A carrier
      males showed higher levels of resting sympathetic cardiac control as compared to
      their G/G counter parts. However, G/G participants displayed significantly higher
      levels of sympathetic reactivity to psychological stress with G/G males showing
      the highest levels of sympathetic response to stress. Although no significant
      effects were detected for heart rate or parasympathetic cardiac control across
      resting and stress conditions, results revealed that G/G participants generally
      displayed heightened stroke volume and cardiac output reactivity to the
      psychological stressor. Furthermore, analysis of diurnal fluctuations in salivary
      cortisol revealed that G/G participants displayed lower awakening cortisol levels
      and less variation in salivary cortisol across the day as compared to A carrier
      individuals.

PMID- 22146103
TI  - Management of cases that might benefit from radiotherapy: a standardised patient
      study in primary care.
AB  - The aim of this study was to assess general practitioner (GP) consultations with
      standardised patients presenting with cancer-related problems that might benefit
      from radiotherapy. Standardised patient scenarios were constructed with
      indications for radiotherapy or with side effects of radiotherapy. Six GPs
      consulted six standardised patients. All consultations were video recorded. Two
      GPs independently rated the consultation performance using the Leicester
      Assessment Package (LAP). Each consultation was also assessed by two radiation
      oncologists to assess specific decisions taken or advice offered to 'patients' in
      each case. The mean duration of consultations was 13 min and 55 s. Three GPs
      differed significantly (P < 0.025) in competencies measured by the LAP, but not
      as assessed by radiation oncologists. There was no significant difference in LAP
      scores when reviewed by scenario. However, there was significant differences in
      the management of the case with prostate cancer (P= 0.005) and data suggest that
      GPs management of different problems presented varied widely. These data are
      consistent with the published literature which suggests that in practice not all
      patients are appropriately advised or referred. There is a need for innovations
      to support GPs to manage patients who would benefit from radiotherapy.

PMID- 22146102
TI  - Application of medical gases in the field of neurobiology.
AB  - Medical gases are pharmaceutical molecules which offer solutions to a wide array
      of medical needs. This can range from use in burn and stroke victims to hypoxia
      therapy in children. More specifically however, gases such as oxygen, helium,
      xenon, and hydrogen have recently come under increased exploration for their
      potential theraputic use with various brain disease states including hypoxia
      ischemia, cerebral hemorrhages, and traumatic brain injuries. As a result, this
      article will review the various advances in medical gas research and discuss the
      potential therapeutic applications and mechanisms with regards to the field of
      neurobiology.

PMID- 22146104
TI  - Aging as a particular case of phenoptosis, the programmed death of an organism (a
      response to Kirkwood and Melov "On the programmed/non-programmed nature of ageing
      within the life history").

PMID- 22146105
TI  - Anaemia during pregnancy: impact on birth outcome and infant haemoglobin level
      during the first 18 months of life.
AB  - To determine the effect of maternal anaemia on pregnancy outcome and describe its
      impact on infant haemoglobin level in the first 18 months of life, we conducted a
      prospective study of 617 pregnant women and their children in Benin. Prevalence
      of maternal anaemia at delivery was 39.5%, and 61.1% of newborns were anaemic at
      birth. Maternal anaemia was not associated with low birth weight [OR = 1.2 (0.6
      2.2)] or preterm birth [OR = 1.3 (0.7-2.4)], whereas the newborn's anaemia was
      related to maternal anaemia [OR = 1.8 (1.2-2.5)]. There was no association
      between an infant's haemoglobin level until 18 months and maternal anaemia.
      However, malaria attacks during follow-up, male gender and sickle cell trait were
      all associated with a lower infant haemoglobin level until 18 months, whereas
      good infant feeding practices and a polygamous family were positively associated
      with a higher haemoglobin level during the first 18 months of life.

PMID- 22146106
TI  - Hydride dissociation energies of six-membered heterocyclic organic hydrides
      predicted by ONIOM-G4Method.
AB  - Hydride dissociation energy is of great importance in understanding the hydride
      donating abilities of organic hydrides. Although the hydride dissociation
      energies of some organic hydrides have been experimentally measured, much less
      attention has been focused on the investigation of these quantities from the
      first principles of physics. Herein, we developed an ONIOM-G4 method and
      carefully benchmarked this new method against 48 experimental hydride
      dissociation energies of diverse bulky molecules. It was found that with the
      combined methods of the HF/6-31+G(d,p)//IEFPCM/Bondi1.15 solvation model, the
      ONIOM-G4 method can predict the hydride dissociation energies with an error bar
      of only 1.7 kcal/mol. With the newly developed ONIOM-G4 method, we then
      systematically studied the hydride dissociation energies of six categories of
      biologically and pharmaceutically important six-membered heterocyclic organic
      hydrides, namely, the organic hydrides containing 1,4-dihydropyridine, 1,4
      dihydropyrazine, 1,4-oxazine, 1,4-thiazine, 4H-pyran, and 4H-thiopyran ring
      structures. An extensive hydride dissociation energy scale containing over 100
      six-memebered heterocyclic organic hydrides has been established, which may find
      applications in both synthetic organic chemistry and mechanistic studies of
      various chemical or biological processes involving transferring of the hydride
      anion.

PMID- 22146107
TI  - Neisseria gonorrhoeae induced disruption of cell junction complexes in epithelial
      cells of the human genital tract.
AB  - Pathogenic microorganisms, such as Neisseria gonorrhoeae, have developed
      mechanisms to alter epithelial barriers in order to reach subepithelial tissues
      for host colonization. The aim of this study was to examine the effects of
      gonococci on cell junction complexes of genital epithelial cells of women.
      Polarized Ishikawa cells, a cell line derived from endometrial epithelium, were
      used for experimental infection. Infected cells displayed a spindle-like shape
      with an irregular distribution, indicating potential alteration of cell-cell
      contacts. Accordingly, analysis by confocal microscopy and cellular fractionation
      revealed that gonococci induced redistribution of the adherens junction proteins
      E-cadherin and its adapter protein beta-catenin from the membrane to a
      cytoplasmic pool, with no significant differences in protein levels. In contrast,
      gonococcal infection did not induce modification of either expression or
      distribution of the tight junction proteins Occludin and ZO-1. Similar results
      were observed for Fallopian tube epithelia. Interestingly, infected Ishikawa
      cells also showed an altered pattern of actin cytoskeleton, observed in the form
      of stress fibers across the cytoplasm, which in turn matched a strong alteration
      on the expression of fibronectin, an adhesive glycoprotein component of
      extracellular matrix. Interestingly, using western blotting, activation of the
      ERK pathway was detected after gonococcal infection while p38 pathway was not
      activated. All effects were pili and Opa independent. Altogether, results
      indicated that gonococcus, as a mechanism of pathogenesis, induced disruption of
      junction complexes with early detaching of E-cadherin and beta-catenin from the
      adherens junction complex, followed by a redistribution and reorganization of
      actin cytoskeleton and fibronectin within the extracellular matrix.

PMID- 22146108
TI  - Computer-based evolutionary search for a nonlinear conversion function for
      establishing in vitro-in vivo correlation (IVIVC) of oral drug formulations.
AB  - Establishment of in vitro-in vivo correlation (IVIVC) accelerates optimization of
      desirable drug formulations and/or modification of the manufacturing processes in
      the scale-up and post-approval periods. This article presents a method of finding
      the optimal conversion function for establishing Level A point-to-point IVIVC,
      based on a computer-based evolutionary search technique. Gene expression
      programming (GEP) is a technique for optimizing a mathematical expression tree
      with the help of a genetic algorithm. A parameter optimization routine, which
      minimizes the number of parameters in the mathematical expression trees and
      estimates the best-fit parameter values, was implemented in the GEP algorithm.
      Feasibility of the computer program was investigated using the in vitro and in
      vivo data for sustained release diltiazem formulations. It provided a
      mathematical equation that, from their in vitro dissolution profiles,
      successfully predicts the plasma concentration profiles of three different
      formulations of diltiazem following oral administration. Because the present
      approach does not use intravenous injection data like conventional IVIVC
      analyses, it is widely applicable to the evaluation of various oral formulations.

PMID- 22146109
TI  - Prediction of human plasma concentration-time profiles of monoclonal antibodies
      from monkey data by a species-invariant time method.
AB  - We have previously reported that human total body clearance (CL) and steady-state
      volume of distribution (Vss) of monoclonal antibodies (mAbs) could be predicted
      reasonably well from monkey data alone using simple allometry with scaling
      exponents of 0.79 and 1.12 (for soluble targets), and 0.96 and 1.00 (for membrane
      bound targets). In the present study, to predict the plasma concentration-time
      profiles of mAbs in humans, we employed simple dose-normalization and species
      invariant time methods (elementary Dedrick plot and complex Dedrick plot), based
      on the monkey data and the scaling exponents we previously determined. The
      results demonstrated that the species-invariant time methods were able to provide
      higher accuracy of prediction than simple dose-normalization, regardless of the
      type of target antigens (soluble or membrane-bound). The accuracy between
      elementary Dedrick plot and complex Dedrick plot was nearly equivalent. The
      predicted human CL and Vss using species-invariant time methods were within
      mostly 2-fold differences from the observed values. The prediction not only of
      pharmacokinetic (PK) parameters but also of the plasma concentration-time profile
      in humans can serve as guidelines for better planning of clinical studies on
      mAbs.

PMID- 22146110
TI  - Association between altered somatosensation, pain, and knee stability in patients
      with severe knee osteoarthrosis.
AB  - OBJECTIVE: To examine the relationship between knee pain, altered
      somatosensation, and self-reported instability in individuals with knee
      osteoarthrosis (OA) during a step-up-and-over task. METHODS: Quantitative sensory
      testing, including mechanical detection threshold (MDT), allodynia, vibration
      perception threshold, and pressure pain threshold (PPT), was assessed in 16
      individuals (mean age, 52 +/- 7 y) with knee OA and in 16 age-matched and sex
      matched controls. Pain intensity ratings and subjective reports of
      instability/buckling were recorded at rest and while performing a step-up task,
      and these findings were correlated with somatosensory measures. RESULTS: In the
      OA group, all participants reported allodynia on MDT testing. Compared with
      healthy controls, MDT was significantly increased (P<0.001), and vibration
      perception threshold was increased (P=0.02) at the medial knee, indicating
      hypoesthesia. PPT was significantly decreased at the medial joint line (P=0.03)
      and 12 cm distal (P=0.02). Comparing participants with OA having severe versus
      mild radiographic changes, PPT was lower at the medial joint line (P<0.01) but
      not at 12 cm distal. Fourteen (87.5%) participants with knee OA reported pain and
      instability during the step task as compared with none or 1 (6%) of the controls.
      On the step task, longer duration of symptoms was associated with increased pain
      (P=0.02). A moderate correlation between greater self-reported instability and
      increased vibratory hypoesthesia at the knee (r=-0.633; P=0.01) was demonstrated,
      suggesting a potential relationship between somatosensory changes and functional
      deficits. CONCLUSIONS: Severe OA may result in both hyperalgesia and hypoesthesia
      at the affected knee. Perceived instability during functional tasks may be
      mediated in part by pain in individuals with knee OA.

PMID- 22146111
TI  - Nutrition screening for seniors in health care facilities: a survey of health
      professionals.
AB  - PURPOSE: Several studies show that malnutrition is prevalent in health care
      facilities, especially among elderly patients and nursing home residents.
      Although validated screening tools exist, little evidence exists on the
      feasibility of implementing nutrition screening in health care facilities. We
      examined New Brunswick health care professionals' perceptions of and practices
      involving nutrition screening in elderly clients, as well as barriers to
      screening. METHODS: A survey was conducted with questionnaires intended for
      physicians, nurses, and dietitians. RESULTS: Participants were 457 health care
      professionals (physicians, 34.6%; nurses, 50.3%; dietitians, 15.1%). Perceptions
      of nutrition screening varied. For example, most nurses (94.7%) and dietitians
      (98.5%) indicated that screening was important/very important, while only 63.5%
      of physicians indicated this. Screening methods also differed among professionals
      and few used a screening tool. Several barriers to implementing nutrition
      screening were reported, such as lack of time, lack of professional resources,
      and clients' short stays. CONCLUSIONS: These findings will help professionals
      address the feasibility of implementing standardized screening tools in health
      care facilities. A more consistent and systematic approach for detecting
      populations at high nutritional risk may result.

PMID- 22146112
TI  - Relative reinforcing value of energy-dense snack foods in overweight and obese
      adults.
AB  - PURPOSE: Obese people find energy-dense food more reinforcing than do their non
      obese peers, and reinforcement influences food intake. We examined how the degree
      of adiposity, measured by body mass index (BMI), is associated with the relative
      reinforcing value of energy-dense snack foods versus fruits and vegetables in
      overweight and obese people. METHODS: Ninety-two overweight or obese students in
      introductory psychology courses completed questionnaires on age, sex, BMI,
      hunger, smoking status, dietary restraint, and hedonic (liking) ratings for
      energy-dense snack foods and fruits and vegetables. The questionnaire also was
      used to evaluate the relative reinforcing value of these snack foods in
      comparison with fruits and vegetables. RESULTS: The BMI predicted the relative
      reinforcing value of energy-dense snack food. This positive relationship remained
      significant after we controlled for age, sex, dietary restraint, hunger, smoking
      status, and snack food hedonics. CONCLUSIONS: The greater the degree of
      overweight and obesity, the greater the motivation to obtain energy-dense snack
      foods. Because the rewarding value of food is a strong determinant of energy
      intake, a useful approach to preventing and treating obesity may be introducing
      pharmacological or behavioural nutrition intervention to reduce the rewarding
      value of energy-dense snack foods, or increasing the rewarding value of fruits
      and vegetables.

PMID- 22146113
TI  - Antioxidant health messages in Canadian women's magazines.
AB  - PURPOSE: Recently, antioxidants have taken centre stage in media and advertising
      messages. While 80% of Canadians think they are well-informed about nutrition,
      many are confused about the health effects of specific nutrients. Forty-six
      percent of Canadians seek information from newspapers and books, and 67% of women
      rely on magazines. We examined the content and accuracy of antioxidant health
      messages in Canadian women's magazines. METHODS: The top three Canadian magazines
      targeted at women readers were selected. A screening tool was developed, pilot
      tested, and used to identify eligible articles. A coding scheme was created to
      define variables, which were coded and analyzed. RESULTS: Seventy-seven percent
      of 36 magazine issues contained articles that mentioned antioxidants (n=56).
      Seventy-one percent (n=40) of articles reported positive health effects related
      to antioxidant consumption, and 36% and 40% of those articles framed those
      effects as definite and potential, respectively (p<0.01). CONCLUSIONS: The
      articles sampled conveyed messages about positive antioxidant health effects that
      are not supported by current evidence. Improved standards of health reporting are
      needed. Nutrition professionals may need to address this inaccuracy when they
      develop communications on antioxidants and health risk.

PMID- 22146114
TI  - Implementing elementary school nutrition policy:  principals' perspectives.
AB  - PURPOSE: We assessed principals' perceptions about the level of school nutrition
      policy (SNP) implementation in Prince Edward Island elementary schools,
      objectively evaluated how closely elementary schools are following SNP
      regulations for types and frequency of foods offered at school, and explored
      principals' beliefs about the key enablers and barriers to SNP implementation.
      METHODS: Phase I involved a cross-sectional survey of principals' assessment of
      perceived and actual adherence to SNP components. Phase II included in-depth
      interviews to explore principals' perceptions about factors influencing policy
      adherence. Descriptive statistics were generated. Thematic content analysis was
      used to identify themes. RESULTS: Forty-one (93%) principals participated in
      Phase I, and nine of these participated in Phase II. The level of implementation
      of SNP components varied. Seventy-four percent of all foods sold were categorized
      as allowed by the SNP; 68% of schools sold at least one "not allowed" food. Key
      barriers included lost revenue, a higher cost of healthy foods, and limited
      availability of policy-allowed foods. Enablers were a high level of community
      support, ready access to food suppliers, and active parent volunteers.
      CONCLUSIONS: While schools are making progress in implementing the SNP,
      challenges remain. Identifying and communicating strategies for healthy
      fundraising activities and finding ways to involve parents in SNP implementation
      are recommended.

PMID- 22146115
TI  - Implementing the Alberta nutrition guidelines for children and youth in a
      recreational facility.
AB  - PURPOSE: In this mixed-methods case study, we explored factors influencing the
      adoption and implementation of the Alberta Nutrition Guidelines for Children and
      Youth within recreational facilities, and assessed the impact of their
      implementation on the food environment. METHODS: Qualitative data were generated
      via interviews, observations, and document reviews. The quality of the food
      environment was assessed using validated and newly developed food environment
      assessment tools. RESULTS: Whereas few barriers existed in terms of adopting the
      guidelines, implementing them proved much more challenging. Implementation was
      impeded by concerns about the lack of profitability of healthy items, time, and
      resource constraints. Guidelines that do not restrict the availability of
      unhealthy options are better accepted by stakeholders. Implementation of the
      guidelines supported creation of a healthy food environment, but the availability
      of healthy items remained very limited within the concession (16%) and vending
      machines (20%), and children continued to purchase primarily unhealthy items.
      CONCLUSIONS: Findings suggest that children choose healthy options insufficiently
      when unhealthy items are present. Thus, although introducing the nutrition
      guidelines in a nonrestrictive format may have been advantageous in some ways,
      they should be strengthened over time so that they recommend near or total
      elimination of unhealthy options.

PMID- 22146116
TI  - Implementing nutrition diagnosis at a multisite health care organization.
AB  - The American Dietetic Association Nutrition Care Process (NCP) is designed to
      improve patient care and interdisciplinary communication through the consistent
      use of standardized nutrition language. Supported by Dietitians of Canada, the
      NCP has been gaining prominence across Canada. In spring 2009, registered
      dietitians at Providence Health Care, an academic, multisite health care
      organization in Vancouver, British Columbia, began using the NCP with a focus on
      nutrition diagnosis. The success of nutrition diagnosis at Providence Health Care
      has depended on support from the Clinical Nutrition Department leadership,
      commitment from the NCP champions, regularly scheduled lunch-and-learn sessions,
      revised nutrition assessment forms with a section for nutrition diagnosis
      statements, and the Pocket Guide for International Dietetics & Nutrition
      Terminology (IDNT) Reference Manual. Audit results from June through August 2010
      showed a 92% nutrition diagnosis completion rate for acute-care and long-term
      care sites within Providence Health Care. Ongoing audits will be used to evaluate
      the accuracy and quality of nutrition diagnosis statements. This evaluation will
      allow Providence Health Care dietitians to move forward with nutrition
      intervention.

PMID- 22146117
TI  - Weight maintenance through behaviour modification with a cooking course or
      neurolinguistic programming.
AB  - We compared the effect on weight regain of behaviour modification consisting of
      either a gourmet cooking course or neurolinguistic programming (NLP) therapy.
      Fifty-six overweight and obese subjects participated. The first step was a 12
      week weight loss program. Participants achieving at least 8% weight loss were
      randomized to five months of either NLP therapy or a course in gourmet cooking.
      Follow-up occurred after two and three years. Forty-nine participants lost at
      least 8% of their initial body weight and were randomized to the next step. The
      NLP group lost an additional 1.8 kg and the cooking group lost 0.2 kg during the
      five months of weight maintenance (NS). The dropout rate in the cooking group was
      4%, compared with 26% in the NLP group (p=0.04). There was no difference in
      weight maintenance after two and three years of follow-up. In conclusion, weight
      loss in overweight and obese participants was maintained equally efficiently with
      a healthy cooking course or NLP therapy, but the dropout rate was lower during
      the active cooking treatment.

PMID- 22146118
TI  - Developing an interview guide to evaluate practice-based evidence in nutrition:
      use of the delphi technique.
AB  - An interview guide was created for qualitative evaluation of the impact of
      Practice-based Evidence in Nutrition (PEN) on dietetic practice, and its success
      as a medium for knowledge translation and transfer (KTT). The Delphi technique
      was used to bring together a diverse group of experts (n=7) with extensive
      knowledge in KTT and evidence-based practice (EBP); these experts developed the
      interview guide content. The technique is an effective means of gathering expert
      input to inform evaluation tool development, particularly in the absence of
      accepted evaluation guidelines or pre-existing evaluation tools. Although
      challenges exist with the Delphi technique, it is an adaptable method that can be
      modified to meet a variety of needs. During this project, the technique was
      modified to meet specific needs, including participants' partial anonymity and
      starting material to reduce the number of required rounds. The resulting
      interview guide contained open-ended questions focused on respondents'
      understanding of EBP and PEN, use of PEN by dietitians in other disciplines,
      perceptions of the quality/usefulness of PEN, and barriers to and facilitators of
      PEN use.

PMID- 22146119
TI  - Evaluation of a family education program for overweight children and adolescents.
AB  - Increased child and youth overweight and obesity, as well as significant health
      effects associated with obesity, have led to recommendations for multicomponent
      prevention programs. In 2005 to 2006, the former Calgary Health Region (now
      Alberta Health Services) had an opportunity to develop, deliver, and evaluate an
      early intervention service for families with children at risk for overweight and
      obesity. Using available evidence and with access to key advisors, core team
      members developed and implemented a curriculum for a family-focused, behaviour
      based education program entitled Make It HAPPEN. A health-centred approach based
      on the physical, mental, and social well-being of the whole child was used.
      Physical, self-esteem, and quality-of-life measures were included in program
      evaluation. After the program, statistically significant reductions in body mass
      index (BMI) percentile and z-score were seen, as were increases in quality of
      life. Self-esteem improved significantly for children with initial BMI
      percentiles of at least 98. Evaluation results indicate that an effective program
      can be developed with limited resources to meet best practice needs. Potentially,
      such programs could be integrated into other community obesity prevention
      programs or within primary health services models.

PMID- 22146120
TI  - Knowledge and use of folic acid in women of reproductive age.
AB  - Folic acid reduces the risk of neural tube defects. As approximately 50% of
      pregnancies are unintended, women of reproductive age should be aware of the
      importance of folic acid. We reviewed the existing literature on these women's
      knowledge of folic acid and neural tube defects. Databases searched were PubMed,
      CINAHL, and Health Reference Center Academic. We used terms such as "folic acid
      knowledge" and "folic acid awareness" to search articles published from 1998 to
      2010. Awareness of the benefits of folic acid before conception and during
      pregnancy was low, although knowledge levels were associated with education and
      household income. Women who were already knowledgeable about folic acid cited
      health care professionals, magazines and newspapers, and radio and television as
      common sources of information. Effective knowledge translation is needed to
      ensure that women are informed about the benefits of folic acid during the
      reproductive years. This knowledge will allow them to make informed decisions
      about folic acid consumption. Health care professionals play an influential role
      in promoting folic acid knowledge among women of childbearing age. Lower levels
      of knowledge among women with lower levels of education and/or household income
      must be addressed.

PMID- 22146121
TI  - n-3 polyunsaturated fatty acids increase thermic effect of food in men with
      metabolic syndrome.
AB  - PURPOSE: Effects on energy metabolism of a test meal and a two-week dietary
      intervention were observed in men with metabolic syndrome (MetS). Both the meal
      and the intervention included foods containing fish-derived n-3 polyunsaturated
      fats (PUFA). METHODS: Six men with MetS (46.7 +/- 12.1 years, 37.2 +/- 5.6
      kg/m(2), mean +/- standard deviation) completed two test days, separated by a 14
      day dietary intervention during which they consumed at least 2.0 g per day of n-3
      PUFA from supplied foods. Pre- and post-intervention measurements included body
      composition, resting metabolic rate (RMR), and the thermic effect of food (TEF)
      measured for six hours after ingestion of a test meal consisting of 1.43 g of
      fish-derived n-3 PUFA. RESULTS: Intakes of n-3 PUFA increased over the 14-day
      intervention, from 0.43 g per day +/- 0.48 to 2.92 g per day +/- 1.97 (p=0.013),
      while no changes were observed in total energy intakes, weight, body composition,
      or RMR (all p>0.05). The TEF increased by 51.3% (p=0.036), and the non-protein
      respiratory quotient decreased by 36.0% (p=0.700). CONCLUSIONS: Subjects
      increased their intake of fish-derived n-3 PUFA in an isocaloric manner while
      maintaining body weight and composition, and increased the TEF. More studies with
      larger sample sizes and longer intervention periods are required to confirm the
      use of fish-derived n-3 PUFA as a therapeutic dietary strategy for people with
      MetS.

PMID- 22146122
TI  - The impact of intestinal resection on serum levels of anti-Saccharomyces
      cerevisiae antibodies (ASCA) in patients with Crohn's disease.
AB  - BACKGROUND: Antibodies to Saccharomyces cerevisiae (ASCA) are highly prevalent in
      sera of patients with Crohn's disease and have been proposed to identify
      subgroups of patients with a disabling disease course. AIM: To investigate the
      impact of intestinal resection on serum levels of ASCA in patients with Crohn's
      disease and the predictive value of ASCA levels on surgical recurrence. METHODS:
      Sera from 60 patients who underwent 'curative' intestinal resection due to
      stricturing and/or penetrating complications were collected preoperatively and
      during post-operative follow-up (week 2, months 4, 8 and 11 +/- 1). Measurement
      of ASCA IgG and IgA isotypes were performed using ELISA. Re-operation rate was
      associated with ASCA status and serum levels. RESULTS: At baseline 44/60 (73%) of
      patients were rated as positive for ASCA IgG, 45/60 (75%) for ASCA IgA and 52/60
      (87%) as positive for at least one of both. ASCA serum levels remained stable
      during first year from resection. After a median of 106 months 10 of 40 (25%)
      patients with long-term follow-up underwent one or more intestinal re-operations.
      Neither ASCA positivity nor absolute ASCA serum levels were predictive of
      surgical recurrence. CONCLUSIONS: Serum ASCA levels remain stable after curative
      intestinal resection in Crohn's disease. This indicates the persistence of both
      stimulus and immunological mechanism operative in the production of ASCA even
      after complete surgical resection of macroscopically inflamed intestinal tissue.
      After intestinal resection, neither ASCA positivity nor ASCA serum levels predict
      the risk of surgical recurrence during long-term follow-up.

PMID- 22146124
TI  - The Fermi surface of [Formula: see text].
AB  - The heavy-fermion compound [Formula: see text] has been studied using the fully
      relativistic spin-polarized mean muffin-tin orbital method within the local
      density approximation. Two separate calculations, one where the f electron is
      treated as a valence electron and the other where it is treated as part of the
      core, have been performed and the Fermi surface is obtained. The angular
      dependent de Haas - van Alphen (dHvA) frequencies are calculated in both cases
      and they are compared with the experimental dHvA frequencies. We also calculated
      the electron momentum densities and compared them with the electron - positron
      momentum densities measured from the two-dimensional angular correlation of
      electron - positron annihilation radiation. The spin polarization of the Fermi
      surface is analysed and we present a new interpretation of the experimental data
      of Harrison  et al.

PMID- 22146123
TI  - Isoflurane does not cause neuroapoptosis but reduces astroglial processes in
      young adult mice.
AB  - BACKGROUND: Isoflurane, a volatile anesthetic widely used clinically, has been
      implicated to be both neuroprotective and neurotoxic. The claim about isoflurane
      causing neural apoptosis remains controversial. In this study, we investigated
      the effects of isoflurane exposures on apoptotic and anti-apoptotic signals, cell
      proliferation and neurogenesis, and astroglial processes in young adult mouse
      brains. METHODS: Sixty 6-week-old mice were randomly assigned to four anesthetic
      concentration groups (0 as control and 0.6%, 1.3%, and 2%) with four recovery
      times (2 h and 1, 6, and 14 d) after 2-h isoflurane exposure.
      Immunohistochemistry measurements of activated caspase-3 and Bcl-xl for apoptotic
      and anti-apoptotic signals, respectively, glial fibrillary acidic protein (GFAP)
      and vimentin for reactive astrocytosis, doublecortin (Dcx) for neurogenesis, and
      BrdU for cell proliferation were performed. RESULTS: Contrary to the previous
      conclusion derived from studies with neonatal rodents, we found no evidence of
      isoflurane-induced apoptosis in the adult mouse brain. Neurogenesis in the
      subgranule zone of the dentate gyrus was not affected by isoflurane. However,
      there is a tendency of reduced cell proliferation after 2% isoflurane exposure.
      VIM and GFAP staining showed that isoflurane exposure caused a delayed reduction
      of astroglial processes in the hippocampus and dentate gyrus. CONCLUSION: Two
      hour exposure to isoflurane did not cause neuroapoptosis in adult brains. The
      delayed reduction in astroglial processes after isoflurane exposure may explain
      why some volatile anesthetics can confer neuroprotection after experimental
      stroke because reduced glial scarring facilitates better long-term neuronal
      recoveries.

PMID- 22146125
TI  - 17-O-demethylreblastatin, a subnormal intermediate in geldanamycin biosynthesis.

PMID- 22146126
TI  - Characterization of a novel gene related to antibiotic susceptibility in
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a human pathogen with increased intrinsic resistance to
      a large number of antibiotics used in clinical therapy. Therefore, understanding
      the mechanisms of resistance and developing therapy alternatives for P.
      aeruginosa are of profound importance. Previous work from our laboratory
      demonstrated that several mutants have isolated with altered expression of the
      phzA1B1C1D1E1F1G1 (phzA1) operon in the presence of sub-inhibitory concentrations
      (SICs) of tetracycline (TET). The present study investigates the roles of the
      PA0011 gene in mediating phzA1 expression at SIC of TET. The PA0011 gene encodes
      2-OH-lauroytransferase by controlling the synthesis of the cell envelope and the
      outer membrane. We found that the PA0011 mutant strain was susceptible to several
      different antibiotics and environmental stresses. Complementation in the PA0011
      mutant restored these phenotypes to wild-type levels. In addition, expression of
      the PA0011 gene, as monitored through a luciferase reporter, is increased at SICs
      of antibiotics. Indeed, the expression of the PA0011 gene increased about
      threefold in pqsR and pqsH mutants compared with the wild-type PAO1. However, the
      PA0011 gene negatively regulates the quorum sensing (QS) system. Taken together,
      these data suggest that PA0011 is involved in susceptibility to antimicrobial
      agents in P. aeruginosa, and that its susceptibility effect maybe partly
      dependent on increased QS expression.

PMID- 22146127
TI  - Effect of intravitreal bevacizumab on retrobulbar blood flow in injected and
      uninjected fellow eyes of patients with neovascular age-related macular
      degeneration.
AB  - BACKGROUND: To determine the effect of intravitreal administration of bevacizumab
      (1.25 mg/0.05 mL) on retrobulbar circulation of the injected and the fellow
      (uninjected) eyes in patients with neovascular age-related macular degeneration.
      METHODS: In this prospective study, the retrobulbar hemodynamics of 43 patients
      with neovascular age-related macular degeneration was examined by color Doppler
      ultrasonography. Peak systolic velocity, end-diastolic velocity, and resistive
      index values in the central retinal artery and short posterior ciliary artery in
      both injected and uninjected fellow eyes were measured at baseline and 7 days
      after a single intravitreal injection of bevacizumab. RESULTS: At baseline, the
      peak systolic velocity, end-diastolic velocity, and the resistive index in the
      central retinal artery and short posterior ciliary artery of the injected eye
      were not significantly different compared with the fellow uninjected eye (P >
      0.05 for all). However, intravitreal bevacizumab induced a significant reduction
      in the peak systolic velocity and end-diastolic velocity and a significant rise
      in the resistive index of the central retinal artery and short posterior ciliary
      artery of the injected eye (P <= 0.006 for all). Peak systolic velocity and end
      diastolic velocity decreased in the central retinal artery (P = 0.023 and P =
      0.030) and the short posterior ciliary artery (P = 0.001 and P < 0.000) in the
      uninjected eye while the resistive index did not significantly change in central
      retinal artery (P = 0.114) and short posterior ciliary artery (P = 0.082) of the
      fellow eyes. CONCLUSION: Intravitreal injection of bevacizumab significantly
      affects ocular hemodynamic parameters of both the injected and the uninjected
      fellow eyes with neovascular age-related macular degeneration.

PMID- 22146128
TI  - Treatment of amelanotic choroidal melanoma with photodynamic therapy.
AB  - PURPOSE: To evaluate the effect of photodynamic therapy on amelanotic choroidal
      melanoma. METHODS: Nine patients with posteriorly located amelanotic choroidal
      melanomas, one with a pigmented portion, underwent photodynamic therapy using
      verteporfin as the photosensitizing agent. The basal diameters ranged from 4 mm
      to 16 mm and the heights from 1.3 mm to 5.7 mm. Treatment was repeated until the
      melanoma was completely flat or its height had reached a stable end point. Tumor
      response was assessed by clinical examination, photography, and ultrasonography.
      Annual screening for hepatic metastases was performed. RESULTS: Eight tumors
      demonstrated apparent complete regression over 1 month to 14 months. The
      amelanotic portion of the mixed tumor flattened, whereas the height of the
      pigmented part remained stable at 2 mm. In 8 patients there has been no
      recurrence during follow-up of between 34 months and 81 months. One case
      developed 2 separate local recurrences at 21 months and 34 months. There were no
      serious complications, no patient lost vision after treatment, and none developed
      metastatic disease. CONCLUSION: In this series photodynamic therapy was highly
      effective in causing regression of posteriorly located amelanotic choroidal
      melanomas, without a detrimental effect on vision. While the short-term results
      are encouraging, there is some uncertainty regarding complete tumor destruction
      and long-term efficacy.

PMID- 22146129
TI  - Predictors for tubercular uveitis: a comparison between biopsy-proven cases of
      tubercular and sarcoid uveitis.
AB  - AIM: To look for clinical parameters that will assist in making a diagnosis of
      tubercular or sarcoid uveitis in a South Indian patient population METHODS:
      Retrospective, nonrandomized, comparative study of 51 patients with a diagnosis
      of biopsy-proven tuberculosis and sarcoidosis. These patients had a minimum of 1
      year follow-up after initiating treatment for either disease. Multivariate
      logistic regression analysis was used to determine clinical predictors of
      tubercular uveitis. RESULTS: The mean age group was 47.08 +/- 11.19 years. There
      were 39 women and 12 men in the study. Multivariate logistic regression analysis
      shows likelihood of uveitis being tubercular in etiology using 3 variables:
      Schirmer test >10 mm, retinal vasculitis with areas of multiple, pigmented
      chorioretinal atrophy along blood vessels, and a positive Mantoux test 76.6%.
      CONCLUSION: A combination of Schirmer test >10 mm, retinal vasculitis with areas
      of multiple, pigmented chorioretinal atrophy along blood vessels, and positive
      Mantoux test may be used clinically to differentiate tubercular from sarcoid
      uveitis in our patient population.

PMID- 22146130
TI  - Chronic diseases in elderly men: underreporting and underdiagnosis.
AB  - OBJECTIVE: prevalence estimates for chronic diseases and associated risk factors
      are needed for priority setting and disease prevention strategies. The aim of
      this cross-sectional study was to estimate the self-reported and clinical
      prevalence of common chronic disorders in elderly men. STUDY DESIGN AND SETTING:
      a questionnaire was sent to a random sample of 4,975 men aged 60-74 years. An age
      stratified randomised sample (n = 1,845) of those with complete questionnaires
      was invited to participate in a telephone interview (n = 864), followed by
      physical examination (n = 600). Self-reported data on risk factors and disease
      prevalence were compared with data from hospital medical records. RESULTS:
      physical inactivity, smoking and excessive alcohol intake were reported by 27, 22
      and 17% of the study population, respectively. Except for diabetes, all the
      chronic diseases investigated, including hypertension, musculoskeletal and
      respiratory diseases were underreported by study participants. Erectile
      dysfunction and hypogonadism were substantially underreported in the study
      population even though these diseases were found to affect 48 and 21% of the
      participants, respectively. CONCLUSIONS: the study showed a high prevalence of
      detrimental life style factors including smoking, excessive alcohol consumption
      and physical inactivity in elderly Danish men. Except for diabetes and
      respiratory disease, chronic diseases were underreported and in particular
      erectile dysfunction and osteoporosis were underdiagnosed in the study
      population, underlining the importance of awareness of chronic diseases among
      both the general population and physicians.

PMID- 22146131
TI  - Hyperbaric oxygen therapy promotes neurogenesis: where do we stand?
AB  - Neurogenesis in adults, initiated by injury to the central nervous system (CNS)
      presents an autologous repair mechanism. It has been suggested that hyperbaric
      oxygen therapy (HBOT) enhances neurogenesis which accordingly may improve
      functional outcome after CNS injury. In this present article we aim to review
      experimental as well as clinical studies on the subject of HBOT and neurogenesis.
      We demonstrate hypothetical mechanism of HBOT on cellular transcription factors
      including hypoxia-inducible factors (HIFs) and cAMP response element binding
      (CREB). We furthermore reveal the discrepancy between experimental findings and
      clinical trials in regards of HBOT. Further translational preclinical studies
      followed by improved clinical trials are needed to elucidate potential benefits
      of HBOT.

PMID- 22146132
TI  - [Renal tolerance of targeted therapies].
AB  - The use of targeted therapies is increasing in the treatment of cancer.
      Monoclonal antibodies and tyrosine kinase inhibitors are the most commonly used
      but other classes such as mTOR inhibitors are increasingly prescribed. These
      treatments are often given in the long term in metastatic and maintenance
      treatments. It is therefore important to monitor the occurrence of immediate
      toxicities but also later and cumulative toxicities. Renal toxicities of targeted
      therapies are most often due to structural damages of the nephron. The anti
      epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth
      factor receptor (VEGFR) have renal side effects since growth factor receptors are
      expressed in the kidney. The toxicity of molecules such as bortezomib, erlotinib
      and lapatinib are less known. The approvals by the Food and Drugs Administration
      (FDA) and European Medicines Agency (EMA) of sorafenib, sunitinib and
      temsirolimus were based on studies of less than 3,000 patients. In this context,
      there is little data on their acute and chronic tolerance, including on the
      kidneys. This short review synthesizes the physiopathological hypotheses, early
      diagnosis and treatment of renal toxicity of major targeted therapies available
      in 2011.

PMID- 22146133
TI  - Neuroprotective effects of dehydroepiandrosterone (DHEA) in rat model of
      Alzheimer's disease.
AB  - The current study was undertaken to elucidate a possible neuroprotective role of
      dehydroepiandrosterone (DHEA) against the development of Alzheimer's disease in
      experimental rat model. Alzheimer's disease was produced in young female
      ovariectomized rats by intraperitoneal administration of AlCl(3) (4.2 mg/kg body
      weight) daily for 12 weeks. Half of these animals also received orally DHEA (250
      mg/kg body weight, three times weekly) for 18 weeks. Control groups of animals
      received either DHAE alone, or no DHEA, or were not ovariectomized. After such
      treatment the animals were analyzed for oxidative stress biomarkers such as
      hydrogen peroxide, nitric oxide and malondialdehyde, total antioxidant capacity,
      reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide
      dismutase and catalase activities, antiapoptotic marker Bcl-2 and brain derived
      neurotrophic factor. Also brain cholinergic markers (acetylcholinesterase and
      acetylcholine) were determined. The results revealed significant increase in
      oxidative stress parameters associated with significant decrease in the
      antioxidant enzyme activities in Al-intoxicated ovariectomized rats. Significant
      depletion in brain Bcl-2 and brain-derived neurotrophic factor levels were also
      detected. Moreover, significant elevations in brain acetylcholinesterase activity
      accompanied with significant reduction in acetylcholine level were recorded.
      Significant amelioration in all investigated parameters was detected as a result
      of treatment of Al-intoxicated ovariectomized rats with DHEA. These results were
      confirmed by histological examination of brain sections. These results clearly
      indicate a neuroprotective effect of DHEA against Alzheimer's disease.

PMID- 22146134
TI  - How the RNA isolation method can affect microRNA microarray results.
AB  - The quality of RNA is crucial in gene expression experiments. RNA degradation
      interferes in the measurement of gene expression, and in this context, microRNA
      quantification can lead to an incorrect estimation. In the present study, two
      different RNA isolation methods were used to perform microRNA microarray analysis
      on porcine brain tissue. One method is a phenol-guanidine isothiocyanate-based
      procedure that permits isolation of total RNA. The second method, miRVanaTM
      microRNA isolation, is column based and recovers the small RNA fraction alone. We
      found that microarray analyses give different results that depend on the RNA
      fraction used, in particular because some microRNAs appear very sensitive to the
      RNA isolation method. We conclude that precautions need to be taken when
      comparing microarray studies based on RNA isolated with different methods.

PMID- 22146135
TI  - A novel alkaline protease with antiproliferative activity from fresh fruiting
      bodies of the toxic wild mushroom Amanita farinosa.
AB  - A novel protease with a molecular mass of 15 kDa was purified from fresh fruiting
      bodies of the wild mushroom Amanita farinosa. The purification protocol entailed
      anion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi
      gel blue gel, cation exchange chromatography on SP-Sepharose, and gel filtration
      by fast protein liquid chromatography on Superdex 75. The protease was unadsorbed
      on DEAE-cellulose but adsorbed on Affi-gel blue gel and SP-Sepharose. It
      demonstrated a single 15-kDa band in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS/PAGE) and a 15-kDa peak in gel filtration. The optimal pH
      and optimal temperature of the protease were pH 8.0 and 65  degrees C,
      respectively. Proliferation of human hepatoma HepG2 cells was inhibited by the
      protease with an IC(50) of 25 uM. The protease did not have antifungal or
      ribonuclease activity.

PMID- 22146136
TI  - In vitro effects of compounds isolated from Sideritis brevibracteata on bovine
      kidney cortex glutathione reductase.
AB  - Glutathione reductase (GR, E.C 1.6.4.2) is a flavoprotein that catalyzes NADPH
      dependent reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH).
      The aim of this study was to investigate in vitro effects of phenolic compounds
      isolated from Sideritis brevibracteata on bovine kidney GR. The Sideritis species
      are widely found in nature and commonly used as medicinal plants. 7-O-glycosides
      of 8-OH-flavones (hypolaetin, isoscutellarein and 3'-hydroxy-4'-O
      methylisoscutellarein) were isolated from aerial parts of Sideritis
      brevibracteata. These compounds inhibited bovine kidney cortex GR in a
      concentration-dependent manner. Kinetic characterization of the inhibition was
      also performed.

PMID- 22146137
TI  - Tyrosine phosphatases as a superfamily of tumor suppressors in colorectal cancer.
AB  - Phosphorylation and dephosphorylation processes catalyzed by numerous kinases and
      phosphorylases are essential for cell homeostasis and may lead to disturbances in
      a variety of vital cellular pathways, such as cell proliferation and
      differentiation, and thus to complex diseases including cancer. As over 80 % of
      all oncogenes encode protein tyrosine kinases (PTKs), protein tyrosine
      phosphatases (PTPs), which can reverse the effects of tyrosine kinases, are very
      important tumor suppressors. Alterations in tyrosine kinase and phosphatase genes
      including point mutations, changes in epigenetic regulation, as well as
      chromosomal aberrations involving regions critical to these genes, are frequently
      observed in a variety of cancers. Colorectal cancer (CRC) is one of the most
      common cancers in humans. CRCs occur in a familial (about 15 % of all cases),
      hereditary (about 5%) and sporadic (almost 75-80 %) form. As genetic
      environmental interrelations play an important role in the susceptibility to
      sporadic forms of CRCs, many studies are focused on genetic alterations in such
      tumors. Mutational analysis of the tyrosine phosphatome in CRCs has identified
      somatic mutations in PTPRG, PTPRT, PTPN3, PTPN13 and PTPN14. The majority of
      these mutations result in a loss of protein function. Also, alterations in the
      expression of these genes, such as decreased expression of PTPRR, PTPRO, PTPRG
      and PTPRD, mediated by epigenetic mechanisms have been observed in a variety of
      tumors. Since cancer is a social and global problem, there will be a growing
      number of studies on alterations in the candidate cancer genes, including protein
      kinases and phosphatases, to determine the origin, biology and potential pathways
      for targeted anticancer therapy.

PMID- 22146138
TI  - Inhibition of genistein glucuronidation by bisphenol A in human and rat liver
      microsomes.
AB  - Genistein is a natural phytoestrogen of the soybean, and bisphenol A (BPA) is a
      synthetic chemical used in the production of polycarbonate plastics. Both
      genistein and BPA disrupt the endocrine system in vivo and in vitro. Growing
      concerns of altered xenobiotic metabolism due to concomitant exposures from soy
      milk in BPA-laden baby bottles has warranted the investigation of the
      glucuronidation rate of genistein in the absence and presence (25 MUM) of BPA by
      human liver microsomes (HLM) and rat liver microsomes (RLM). HLM yield V(max)
      values of 0.93 +/- 0.10 nmol . min(-1) . mg(-1) and 0.62 +/- 0.05 nmol . min(-1)
      . mg(-1) in the absence and presence of BPA, respectively. K(m) values for
      genistein glucuronidation by HLM in the absence and presence of BPA are 15.1 +/-
      7.9 MUM and 21.5 +/- 7.7 MUM, respectively, resulting in a K(i) value of 58.7 MUM
      for BPA. Significantly reduced V(max) and unchanged K(m) in the presence of BPA
      in HLM are suggestive of noncompetitive inhibition. In RLM, the presence of BPA
      resulted in a K(i) of 35.7 MUM, an insignificant change in V(max) (2.91 +/- 0.26
      nmol . min(-1) . mg(-1) and 3.05 +/- 0.41 nmol . min(-1) . mg(-1) in the absence
      and presence of BPA, respectively), and an increase in apparent K(m) (49.4 +/- 14
      MUM with no BPA and 84.0 +/- 28 MUM with BPA), indicative of competitive
      inhibition. These findings are significant because they suggest that BPA is
      capable of inhibiting the glucuronidation of genistein in vitro, and that the
      type of inhibition is different between HLM and RLM.

PMID- 22146139
TI  - Bacterial community structure and bamA gene diversity in anaerobic degradation of
      toluene and benzoate under denitrifying conditions.
AB  - AIM: To characterize the microbial community structure and bamA gene diversity
      involved in anaerobic degradation of toluene and benzoate under denitrifying
      conditions. METHODS AND RESULTS: Nitrate-reducing enrichment cultures were
      established on either toluene, benzoate or without additional substrate.
      Bacterial community structures were characterized by 16S rRNA gene-based PCR-DGGE
      analysis. bamA gene diversity was analysed using DGGE and cloning methods. The
      results showed that bamA gene related to bamA of Thauera chlorobenzoica was
      dominant in toluene and benzoate cultures. However, a greater diversity of
      sequences was obtained in benzoate cultures. Low diversity of bamA gene was
      observed, and some similarities of bamA were also found between active cultures
      and backgrounds, suggesting that potential natural attenuation of aromatic
      compounds might occur. CONCLUSIONS: The combined analysis of 16S rRNA and bamA
      genes suggests that the species related to genera Thauera dominated toluene- and
      benzoate-degrading cultures. The combination of multiple methods (DGGE and
      cloning) provides a more complete picture of bamA gene diversity. SIGNIFICANCE
      AND IMPACT OF THE STUDY: To our knowledge, this is the first report of bamA gene
      in denitrifying enrichments using DGGE and cloning analysis.

PMID- 22146140
TI  - Age-related leaf characteristics of surface features and ultrastructure of
      Dendropanax morbifera.
AB  - Age-related morphological and anatomical changes were investigated by light and
      electron microscopy with juvenile and adult leaves of Dendropanax morbifera. Most
      juvenile leaves were glossy and palmate with five deep and narrow lobes divided
      nearly to two-thirds of the leaf base. Adult leaves were thick and possessed
      three lobes divided nearly to half of the leaf base. Stomata were ovoid and found
      on the abaxial surface. The epicuticular waxes of the plant included platelets,
      angular rodlets and threads. Platelets were attached to the surface at various
      angles. Distinct angular rodlets could be found on either the adaxial or the
      abaxial surface. Platelets on surface undulations occurred exclusively on the
      abaxial surface of adult leaves. Juvenile leaves were ca. 150 MUm thick and had
      few intercellular spaces. Adult leaves were nearly two times thicker than
      juvenile leaves, and showed highly vacuolated cells and large intercellular
      spaces. The cuticle proper was apparent on the epidermis and showed distinctly
      alternating lamellate structures in juvenile leaves. The epidermal cell wall of
      adult leaves was covered with a cuticle layer for which a lamellate structure was
      not found. These results suggest that the species is heteroblastic in leaf
      characteristics with increasing leaf age.

PMID- 22146142
TI  - A comparison of the recognition of overwork-related cardiovascular disease in
      Japan, Korea, and Taiwan.
AB  - In Japan, Korea, and Taiwan, cerebrovascular and cardiovascular diseases (CVDs)
      caused by overwork are recognized by government as work-related. These three
      countries are the only countries in the world that officially recognize CVDs
      caused by psychosocial factors (e.g., overwork) as work-related cerebrovascular
      and cardiovascular diseases (WR-CVDs), and compensate employees accordingly. The
      present study compared the similarities and differences among the recognition of
      overwork-related CVDs in Japan, Korea, and Taiwan. The criteria by which WR-CVDs
      are identified are very similar in the three countries. However, in the interval
      surveyed (1996-2009), Korea had a remarkably larger number of recognized WR-CVD
      patients than did Japan or Taiwan. Recognition of occupational diseases is
      influenced by various factors, including socio-cultural values, the nature of
      occupational health care schemes, the extent of the social security umbrella,
      national health insurance policy, and scientific evidence. Our results show that
      social factors may be very different among the three countries studied, although
      the recognition criteria for WR-CVDs are quite similar.

PMID- 22146141
TI  - Neonatal brainstem dysfunction risks infant social engagement.
AB  - The role of the brainstem in mediating social signaling in phylogenetic ancestral
      organisms has been demonstrated. Evidence for its involvement in social
      engagement in human infants may deepen the understanding of the evolutionary
      pathway of humans as social beings. In this longitudinal study, neonatal
      brainstem functioning was measured by auditory brainstem-evoked responses (ABRs)
      in 125 healthy neonates born prematurely before 35 weeks' gestational age. At 4
      months, infants were tested in a set of structured vignettes that required
      varying levels of social engagement and cardiac vagal tone was assessed. Data
      show that neonates with a disrupted I-V waveform, evident mostly by delayed wave
      V, exhibit shorter latencies to gaze averts in episodes involving direct face-to
      face interactions but engage gaze as controls when interacting with masked agents
      or with agents whose faces are partly veiled by toys. Analysis of variance of
      infants' social engagement with ABR, neonatal risk, maternal stress and cardiac
      vagal tone showed a main effect for ABR and an ABR by gestational age
      interaction. The integrity of brainstem transmission of sensory information
      during the final weeks of gestation may scaffold the development of social
      disengagement, thereby attesting to the brainstem's preserved evolutionary role
      in developing humans as social organisms prior to engaging in social encounters.

PMID- 22146143
TI  - Analysis of bronchoalveolar lavage fluid adhering to lung surfactant. Experiment
      on intratracheal instillation of nickel oxide with different diameters.
AB  - Nickel oxide with two different particle sizes, micron size (NiO) and submicron
      size (nNiOm), as well as crystalline silica as a positive control and titanium
      dioxide as a negative control, were intratracheally instilled in rats and the
      phospholipid concentration and the protein concentration and surface tension of
      bronchoalveolar lavage fluid (BALF), which are used in surfactant assessment,
      were measured to see if they could be effective biomarkers in toxicity
      assessment. The results showed that the NiO instilled group showed no significant
      difference compared to the control group throughout the observation period. In
      contrast, a significant difference was found in the nNiOm instilled group
      compared to the control group throughout the observation period. Moreover, a
      significant difference was found in the crystalline silica instilled group for
      each measurement compared to the control group while for the titanium dioxide
      group, almost no significant difference was found. These results indicate that
      submicronsized particles of nickel oxide with smaller median diameters
      potentially have a stronger biological effect than micron size particles. They
      also indicate that screening can be done by measuring the phospholipid
      concentration and the protein concentration and surface tension of BALF.

PMID- 22146144
TI  - Recovery after three-shift work: relation to sleep-related cardiac neuronal
      regulation in nurses.
AB  - This study was to evaluate whether sleep-related autonomic function in nurses
      recovers during their days off following a rapidly rotating, clockwise shift
      schedule. Ten rotating-shift nurses and ten regular morning-shift nurses were
      included. Nurses slept at home and were allowed to sleep and wake spontaneously.
      For the rotating-shift workers, ambulatory polysomnographic recordings were taken
      during nighttime sleep (after the second morning shift, afternoon shift, and on
      days off) and during daytime sleep (after the second night shift). No significant
      differences were found between regular-shift nurses and rotating-shift nurses in
      terms of sleep patterns and cardiac autonomic functions during day shift. When
      comparing sleep patterns within shift groups, the total sleep time of night shift
      was lower than their other shifts. Controlling for the variable of total sleep
      time allowed us to compare cardiac autonomic functions following different shifts
      (for the rotating shift nurses). During the non-rapid eye movement and rapid eye
      movement periods, the high frequency (HF) value on rotating shift nurses' days
      off was found to be significantly higher than their other shifts. However, the
      low to high frequency ratio (LF/HF) on days off was found to be obviously lower
      than that during shift work. Two consecutive days off may be sufficient for
      nurses to recover sleep-related autonomic functions after a rapidly rotating,
      clockwise three-shift schedule. Sleep-related autonomic functions may be improved
      during days off to minimize health risks.

PMID- 22146145
TI  - Biodynamic response of the seated human body to single-axis and dual-axis
      vibration: effect of backrest and non-linearity.
AB  - The biodynamic responses to the human body give an understanding of why human
      responses to vibration (changes in health, comfort, and performance) vary with
      the frequency and direction of vibration. Studies have shown that biodynamic
      responses also vary with the magnitude of vibration and that the backrests of
      seats influence the transmission of vibration to the seated human body. There has
      been little study of the nonlinearity in the biodynamic responses of the body to
      dual-axis excitation and no study of the influence of backrests during dual-axis
      excitation. This study investigated the apparent mass and cross-axis apparent
      mass of the human body exposed to random vibration (0.2 to 20 Hz) in all 15
      possible combinations of four magnitudes (0, 0.25, 0.5 and 1.0 ms(-2) r.m.s.) of
      fore-and-aft vibration and the same four magnitudes of vertical vibration.
      Nonlinearity was evident, with the body softening with increasing magnitude of
      vibration when using a fixed magnitude of vibration in one direction and varying
      the magnitude of vibration in the other direction. The fore-and-aft apparent mass
      on the seat was greater without a backrest at the lower frequencies but greater
      with a backrest at the higher frequencies. The vertical apparent mass on the seat
      was decreased by the backrest at low frequencies. Cross-axis coupling was
      evident, with excitation in one axis producing a response in the other axis. It
      is concluded that the nonlinearity of the body evident during single-axis and
      multi-axis vibration, and the influence of backrests, should be taken into
      account when determining frequency weightings for predicting human responses to
      vibration and when optimising the dynamics of seating to minimise exposure to
      vibration.

PMID- 22146146
TI  - Variability in total dust exposure in a cement factory.
AB  - Exposure assessment is a main component of epidemiologic studies and variability
      in exposure. This assessment is considered as a common approach for such
      phenomenon. A total of 129 dust samples were collected randomly from 197
      personnel from a cement factory located in Ilam province, during 2009 in Iran.
      The between- and within-group components of variability were determined to assess
      the contrast in exposure level between the Similar Exposure Groups (SEGs) and to
      calculate the within-worker geometric standard deviation of the theoretical
      exposure-response slope. Results were analyzing by one-way random effects model.
      According to the mentioned model, the probability of long-term mean exposure
      exceeding to the occupational exposure limit (OEL) was assessed for each SEGs.
      The arithmetic means (AM) of total dust levels ranged from 0.04 to 39.37 mg/m(3).
      The geometric means (GM) of total dust were higher in the crusher (20.84
      mg/m(3)), packing (17.29 mg/m(3)), kiln (16.78 mg/m(3)), cement mill (14.90
      mg/m(3)), and raw mill (10.44 mg/m(3)). However, the figures for the maintenance
      and administration parts were 3.77 mg/m(3) and 1.01 mg/m(3), respectively. The
      random effects model data demonstrated that the F-value calculated was greater
      than the critical F-value approximately 59% of the variability in the exposure
      was due to differences between groups. Based on these finding, the order of
      probability of the long-term mean exposure exceeding (Z) to the OEL of 10 mg/m(3)
      for total dust which were in kiln (100%), packing (100%), cement mill (90%),
      crusher (73%), raw mill (60%) administration (2.3%) and the maintenance parts
      (0%).

PMID- 22146147
TI  - Congenital absence of gluteal muscles, optic nerve hypoplasia, and central
      nervous system hamartomas.

PMID- 22146148
TI  - Individual patient assessment of methadone-induced QT prolongation with digital
      holter recording.
AB  - A 27-year-old male who had been on methadone therapy for 6 months was
      investigated with a 12-lead digital holter because of a prolonged QT on a
      standard 12-lead electrocardiogram (ECG). The patient had 24-hour holter
      recording on and off methadone therapy and multiple digitized 12-lead ECG data
      were captured for on-screen measurement of the QT interval. For each 24-hour
      period QT-HR pairs were plotted on the QT nomogram showing QT prolongation on
      methadone but not when it was ceased. This provides a highly accurate method for
      evaluating drug-induced QT prolongation.

PMID- 22146149
TI  - Endosulfan upregulates AP-1 binding and ARE-mediated transcription via ERK1/2 and
      p38 activation in HepG2 cells.
AB  - Endosulfan is an organochlorine insecticide and has been implicated in
      neurotoxicity, hepatotoxicity, immunosuppression and teratogenicity. However, the
      molecular mechanism of endosulfan toxicity is not yet clear. Recent studies
      demonstrated that oxidative stress induced by endosulfan is involved in its
      toxicity and accumulating evidence suggests that endosulfan can modulate the
      activities of stress-responsive signal transduction pathways including
      extracellular signal regulated kinases (ERK) 1/2. However, none of the previous
      studies investigated the ability of endosulfan to modulate activating protein-1
      (AP-1) binding and antioxidant response element (ARE)-mediated transcription as
      an underlying mechanism of endosulfan toxicity. In this report, we show that
      treatment of HepG2 cells with endosulfan significantly increased oxidative stress
      responsive transcription via AP-1 activation. In addition, endosulfan-induced
      transcription was enhanced in cells depleted of glutathione by buthionine
      sulfoximine (BSO) treatment. Exposure to endosulfan resulted in a significant
      increase in the activities of MAPKs, ERK1/2 and p38. Endosulfan-induced increases
      in enzymatic activities of these MAPKs were consistent with MAPK phosphorylation.
      Endosulfan exposure also caused an increase in c-Jun phosphorylation. These
      results suggest a model for endosulfan toxicity in which endosulfan increases
      ERK1/2 and p38 activities and these activated MAPKs then increase c-Jun
      phosphorylation. Phosphorylated c-Jun, in turn, increases AP-1 activity, which
      results in activation of ARE-mediated transcription.

PMID- 22146150
TI  - Voxel-wise meta-analysis of fMRI studies in patients at clinical high risk for
      psychosis.
AB  - BACKGROUND: Reliable neurofunctional markers of increased vulnerability to
      psychosis are needed to improve the predictive value of psychosis risk syndrome
      and inform preventive interventions. METHODS: I performed a signed differential
      mapping (SDM) voxel-wise meta-analysis of functional magnetic resonance imaging
      (fMRI) studies of patients at clinical high risk for psychosis. RESULTS: Ten
      studies were included in the analysis. Compared with controls, high-risk patients
      showed reduced neural activation in the left inferior frontal gyrus (Brodmann
      area [BA] 9) and in a cluster spanning the bilateral medial frontal gyrus (BA
      8,6), bilateral superior frontal gyrus (BA 8,6)and the left anterior cingulate
      (BA 32). There was no publication bias. Heterogeneity across studies was low.
      Sensitivity analysis confirmed the robustness of the findings. LIMITATIONS: The
      cross-sectional nature of the included studies prevented the comparison of high
      risk patients who later experienced a psychotic episode with those who did not.
      Other caveats are reflected in methodologic heterogeneity across tasks employed
      by different individual imaging studies. CONCLUSION: Reduced neurofunctional
      activation in prefrontal regions may represent a neurophysiologic correlate of
      increased vulnerability to psychosis.

PMID- 22146151
TI  - Is the Gly82Ser polymorphism in the RAGE gene relevant to schizophrenia and  the 
      personality trait psychoticism?
AB  - BACKGROUND: The receptor for advanced glycation end products (RAGE) is the main
      receptor for S100B, an astrogial proinflammatory mediator that has been suggested
      to be involved in the pathophysiology of schizophrenia. To further elucidate the
      possible relevance of inflammation for mental functions, we investigated a
      functional polymorphism in the gene coding for RAGE in relation to personality
      traits and susceptibility to schizophrenia. METHODS: We studied the Gly82Ser
      polymorphism (rs2070600, 244G>A) in 2 population-based cohorts of middle-aged
      participants assessed using the Karolinska Scales of Personality. In addition, we
      compared genotype frequencies between patients with schizophrenia and controls.
      RESULTS: The population-based cohorts included 270 women and 247 men, and the
      case-control study involved 138 patients with schizophrenia and 258 controls. In
      the population-based cohorts, 82Ser carriers were found to have significantly
      higher scores for the psychoticism personality trait comprising the detachment
      and suspicion subscales. The case-control study revealed that the 82Ser allele
      was significantly more frequent among patients than controls. LIMITATIONS: This
      study was limited by the modest sample size and the use of a self-report measure
      to assess personality traits. CONCLUSION: Our findings suggest that the proven
      relation between certain personality traits and schizophrenia can at least to
      some extent be explained on a genetic level. Also, the activated S100B-RAGE axis
      may be an underlying cause, not only a consequence, of the disease.

PMID- 22146153
TI  - Property value estimation for inhaled therapeutic binary gas mixtures: He, Xe,
      N2O, and N2 with O2.
AB  - BACKGROUND: The property values of therapeutic gas mixtures are important in
      designing devices, defining delivery parameters, and in understanding the
      therapeutic effects. In the medical related literature the vast majority of
      articles related to gas mixtures report property values only for the pure
      substances or estimates based on concentration weighted averages. However, if the
      molecular size or structures of the component gases are very different a more
      accurate estimate should be considered. FINDINGS: In this paper estimates based
      on kinetic theory are provided of density, viscosity, mean free path, thermal
      conductivity, specific heat at constant pressure, and diffusivity over a range of
      concentrations of He-O2, Xe-O2, N2O-O2 and N2-O2 mixtures at room (or normal) and
      body temperature, 20 and 37 degrees C, respectively and at atmospheric pressure.
      CONCLUSIONS: Property value estimations have been provided for therapeutic gas
      mixtures and compared to experimental values obtained from the literature where
      possible.

PMID- 22146152
TI  - Event-related potentials and changes of brain rhythm oscillations during working
      memory activation in patients with first-episode psychosis.
AB  - BACKGROUND: Earlier contributions have documented significant changes in sensory,
      attention-related endogenous event-related potential (ERP) components and theta
      band oscillatory responses during working memory activation in patients with
      schizophrenia. In patients with first-episode psychosis, such studies are still
      scarce and mostly focused on auditory sensory processing. The present study aimed
      to explore whether subtle deficits of cortical activation are present in these
      patients before the decline of working memory performance. METHODS: We assessed
      exogenous and endogenous ERPs and frontal theta event-related synchronization
      (ERS) in patients with first-episode psychosis and healthy controls who
      successfully performed an adapted 2-back working memory task, including 2 visual
      n-backworking memory tasks as well as oddball detection and passive fixation
      tasks. RESULTS: We included 15 patients with first-episode psychosis and 18
      controls in this study. Compared with controls, patients with first-episode
      psychosis displayed increased latencies of early visual ERPs and phasic theta ERS
      culmination peak in all conditions. However, they also showed a rapid recruitment
      of working memory-related neural generators, even in pure attention tasks, as
      indicated by the decreased N200 latency and increased amplitude of sustained
      theta ERS in detection compared with controls. LIMITATIONS: Owing to the limited
      sample size, no distinction was made between patients with first-episode
      psychosis with positive and negative symptoms. Although we controlled for the
      global load of neuroleptics, medication effect cannot be totally ruled out.
      CONCLUSION: The present findings support the concept of a blunted
      electroencephalographic response in patients with first-episode psychosis who
      recruit the maximum neural generators in simple attention conditions without
      being able to modulate their brain activation with increased complexity of
      working memory tasks.

PMID- 22146154
TI  - The effect of Co doping on antiferromagnetic correlations in the Kondo semi-metal
      CeNiSn.
AB  - Single-crystal neutron scattering experiments have been performed to study
      magnetic excitations in [Formula: see text], in which the pseudo-gap of CeNiSn is
      suppressed by the doping. In CeNiSn there are two inelastic excitation peaks at
      [Formula: see text] and 4 meV, which correspond to dynamic antiferromagnetic
      correlations. In [Formula: see text] the 2 meV peak is smeared out, whereas the 4
      meV peak becomes very weak and broad, but preserves the same quasi-one
      dimensional character as that for CeNiSn. These results suggest the strong
      relation between the antiferromagnetic correlations and the pseudo-gap formation.

PMID- 22146155
TI  - Giardia disrupts the arrangement of tight, adherens and desmosomal junction
      proteins of intestinal cells.
AB  - Giardia duodenalis is a parasitic protozoan that causes diarrhea and other
      symptoms which together constitute a disease known as giardiasis. Although the
      disease has been well defined, the mechanisms involving the establishment of the
      infection have not yet been fully elucidated. In this study, we show that after
      24h of interaction between parasites and intestinal Caco-2 cells, there was an
      alteration of the paracellular permeability, as observed by an approximate 42% of
      reduction in the transepithelial electrical resistance and permeation to
      ruthenium red, which was concomitant with ultrastructural changes. Nevertheless,
      epithelium viability was not affected. We also demonstrate that there was no
      change in expression of junctional proteins (tight and adherens) but that the
      distribution of these proteins in Caco-2 cells after parasite adhesion was
      significantly altered, as observed via laser scanning confocal microscopy 3D
      reconstruction. The present work shows that adhesion of Giardia duodenalis
      trophozoites to intestinal cells in vitro induces disturbances of the tight,
      adherens and desmosomal junctions.

PMID- 22146156
TI  - An ocular cysticercosis in Bali, Indonesia caused by Taenia solium Asian
      genotype.
AB  - An ocular cysticercosis case of a nine-year-old Balinese girl in Indonesia is
      reported. She presented with redness and pain in the left eye and showed a
      cysticercus in the anterior chamber in December 2010. Morphological feature of
      the cysticercus removed from the anterior chamber indicated that it was an
      immature cysticercus of Taenia species with no hooklets. However, mitochondrial
      DNA analysis using a piece of histopathological specimen revealed it a
      cysticercus of Taenia solium Asian genotype. Serology by immunoblot and ELISA
      highly specific to cysticercosis was negative.

PMID- 22146157
TI  - Flyway homogenisation or differentiation? Insights from the phylogeny of the
      sandpiper (Charadriiformes: Scolopacidae: Calidrinae) wing louse genus Lunaceps
      (Phthiraptera: Ischnocera).
AB  - The wing louse genus Lunaceps, is the most speciose chewing louse (Phthiraptera)
      genus inhabiting sandpipers (Charadriiformes: Calidrinae) and is known from
      almost all sandpiper species. The hosts follow specific flyways from the Arctic
      breeding grounds to wintering locations in the southern hemisphere, and often
      form large mixed-species flocks during migration and wintering. We estimated a
      phylogeny of Lunaceps based on three mitochondrial loci, supporting monophyly of
      the genus but revealing extensive paraphyly at the species level. We also
      evaluated the relative importance of flyway differentiation (same host species
      having different lice along different flyways) and flyway homogenisation
      (different host species having the same lice along the same flyway). We found
      that while the lice of smaller sandpipers and stints show some evidence of flyway
      homogenisation, those of larger sandpipers do not. No investigated host species
      migrating along more than one flyway showed any evidence of flyway
      differentiation. The host-parasite associations within Lunaceps are in no case
      monophyletic, rejecting strict cospeciation.

PMID- 22146158
TI  - Laparoscopic versus open gastrectomy with D2 lymph node dissection for gastric
      cancer: a meta-analysis.
AB  - BACKGROUND: Nowadays laparoscopic gastrectomy with D2 lymph node dissection
      (LGD2) is used for gastric cancer, which provides an alternative to open radical
      gastrectomy (OGD2). But it has not gained wide acceptance, and its oncological
      safety remains controversial. The aim of this study is to evaluate the efficiency
      and safety of LGD2 through a meta-analysis. MATERIALS AND METHODS: Original
      articles of clinical trials comparing LGD2 and OGD2 for gastric cancer, published
      in English language from January 2001 to April 2010 were searched in the MEDLINE,
      Current Contents, and Pubmed. Strict literature appraisal and data extraction
      were carried out independently by 2 reviewers and then a meta-analysis was
      performed using RevMan 4.2.5 to evaluate the items of operative time, blood loss,
      harvested lymph nodes, analgesic medication, first flatus day, postoperative
      hospital stay, postoperative complications, and cumulative survival rate.
      RESULTS: Ten trials were involved in the meta-analysis, concerning a total of
      1039 patients (495 in LGD2 and 544 in OGD2). Compared with OGD2, LGD2 showed
      advantages of less blood loss during operation [weighed mean difference (WMD), 
      114.98; 95% confidence interval (CI), -160.44 to -69.52; P<0.00001], less
      postoperative pain (WMD, -0.89; 95% CI, -1.54 to -0.32; P=0.002), earlier passage
      of flatus (WMD, -0.84; 95% CI, -1.25 to -0.43; P<0.0001), shorter hospital stay
      (WMD, -3.27; 95% CI, -4.54 to -2.00; P<0.00001), and less postoperative
      complications [odds ratio (OR), 0.56; 95% CI, 0.32-0.59; P=0.03]; but with longer
      operative time [WMD, 57.14; 95% CI, 38.12-76.15; P<0.00001]. There were no
      significant differences between LGD2 and OGD2 in harvested lymph nodes (WMD, 
      2.07; 95% CI, -4.27 to -0.14; P=0.07) and overall survival rate of 11 to 60
      months' follow-up (OR, 1.44; 95% CI, 0.92-2.27; P=0.11). CONCLUSIONS: The results
      of this meta-analysis suggest that LGD2 results in less blood loss and
      postoperative complications and also less pain and faster bowel function
      recovery, with similar harvested lymph nodes and overall survival rate comparing
      to OGD2. However, we also see the need for further high-quality randomized
      controlled trials comparing the 2 procedures.

PMID- 22146159
TI  - Laparoscopic cholecystectomy and liver cirrhosis.
AB  - INTRODUCTION: Historically the presence of liver cirrhosis has been an absolute
      or relative contraindication to laparoscopic cholecystectomy (LC). Accumulating
      experience in LC has resulted in an increasing number of investigators reporting
      that LC can be safely performed in cirrhotic patients. The aim of this study was
      to report the efficacy and safety of LC in the treatment of symptomatic
      cholelithiasis in cirrhotic patients, and a review of the literature in the
      matter. METHODS: Between January 2006 and July 2010, from 503 patients under LC,
      we reviewed 43 cirrhotic patients of Child-Pugh Classification A, B, and C, with
      symptomatic gallstones. RESULTS: Conversion to an open procedure was necessary in
      5 patients due to multiple factors. The mean operative time and length of
      hospital stay were significantly longer and higher in cirrhotic group (P<0.05).
      Postoperative complications were observed in 37.2% of patients. Trocar site
      hematoma (P=0.02), wound complications (P=0.02), and intra-abdominal collection
      (P=0.01) occurred more frequently in patients with cirrhosis (Child B and C
      class) than in patients without cirrhosis. One case of continuing hemorrhage from
      the gallbladder bed required a reoperation for hemostasis. Two patients with
      Child-Pugh class C and 1 patient with class B cirrhosis developed ascites after
      surgery; 1 patient with Child-Pugh class A had bile leakage. No deaths occurred.
      CONCLUSIONS: LC is an effective and safe procedure and should be the treatment of
      choice for symptomatic cholelithiasis or cholecystitis in patients with
      compensated cirrhosis.

PMID- 22146160
TI  - Laparoscopic abdominoperineal resections for mid or low rectal adenocarcinomas: 
      a retrospective, comparative study.
AB  - BACKGROUND: Laparoscopic abdominoperineal resection (APR) has been seldom studied
      apart from low anterior resections, and deserves to be separately analyzed. This
      study aims to compare perioperative and oncological outcomes of laparoscopic and
      conventional APRs performed for the treatment of mid and low rectal
      adenocarcinomas. MATERIALS AND METHODS: Patients operated for primary mid or low
      rectal adenocarcinoma between 2001 and 2009 in our institution were
      retrospectively investigated. These data were abstracted and compared within
      conventional and laparoscopic resection groups: demographics, tumor and procedure
      related parameters, perioperative results, early oncological outcomes, and
      survival. RESULTS: Demographics and tumor and procedure-related parameters were
      similar within the laparoscopic (n=31) and conventional (n=36) groups, except
      intraoperative bleeding and requirement for transfusion, which were significantly
      lower after laparoscopic APRs. Perioperative results including complication,
      reoperation, and 30-day mortality rates were identical. Early oncological results
      and 3-year survival rates were alike. CONCLUSIONS: The perioperative results and
      oncological outcomes are similar after laparoscopic and conventional APRs. As
      current data include limited number of patients in a retrospective design,
      further studies comparing laparoscopic and conventional APR techniques are
      required.

PMID- 22146161
TI  - Laparoscopic right hemicolectomy with transvaginal colon extraction using a
      laparoscopic posterior colpotomy: a 2-year series from a single institution.
AB  - BACKGROUND: In laparoscopic-assisted colon surgery, an abdominal incision is
      needed to remove the specimen and perform an anastomosis. We adopted the
      technique of totally laparoscopic right hemicolectomy and transvaginal extraction
      in women who required right colon resection. METHODS: Over a 2-year period, 14
      women were scheduled for totally laparoscopic right hemicolectomy with
      intracorporeal anastomosis and transvaginal colon removal. The indications for
      surgery included malignant (n=9) and benign (n=5) right-side colon pathology.
      RESULTS: The procedure was accomplished laparoscopically in all patients. In 1
      patient, the transvaginal removal was not possible because of a large tumor mass.
      The American Society of Anesthesiology was III in 13 and II in 1 patient. The
      mean body mass index was 31.65. Seventy-eight percent of patients had undergone
      abdominal surgery previously. The mean size of the lesion was 3.75 cm (range, 1.8
      to 8.0 cm) and the mean number of lymph nodes was 18.7 (range, 8 to 37). All
      margins in the resected specimens were macroscopically and microscopically free
      of any tumor. One patient needed reoperation for intra-abdominal bleeding,
      whereas 3 patients developed postoperative ileus. DISCUSSION: Laparoscopic right
      hemicolectomy and transvaginal extraction is a safe and effective procedure that
      can be added to the armamentarium of surgeons performing laparoscopic colon
      surgery. This technique may provide both an attractive way to reduce abdominal
      wall morbidity and a bridge to pure natural orifice transluminal endoscopic
      surgery for colon surgery.

PMID- 22146162
TI  - Effect of body mass index on short-term outcomes of patients undergoing
      laparoscopic resection for colorectal cancer: a single institution experience in
      Japan.
AB  - BACKGROUND: The impact of body mass index (BMI) on laparoscopic surgery for
      colorectal cancer in Asian countries is unclear, partly because obesity is less
      common in Asia than in western countries. The purpose of this study was to
      evaluate the association between BMI and short-term outcomes after laparoscopic
      resection for colorectal cancer in Japanese patients. METHODS: A cohort of 1194
      patients who underwent laparoscopic resection for colorectal cancer at Cancer
      Institute Hospital between July 2005 and February 2010 were enrolled in this
      prospective study. Outcomes were analyzed according to BMI category: nonobese
      (BMI<25), obese I (25 <= BMI < 30), and obese II (BMI >= 30). RESULTS: A total of
      926 patients (78%) were classified as nonobese, 243 (20%) were obese I, and 25
      (2%) were obese II. Mean operating time (214 min vs. 244 min vs. 293 min) and
      mean estimated blood loss (23 mL vs. 42 mL vs. 88 mL) increased significantly
      with increasing BMI (P<0.0001, respectively). The rate of postoperative
      complications was significantly higher in obese II patients than in nonobese and
      obese I patients (24% vs. 9.2% vs. 9.1%, P=0.0428). Multivariate analysis showed
      that a BMI in the obese II range was an independent predictive factor for
      developing anastomotic leakage (odds ratio: 10.27, 95% confidence interval, 1.98
      53.44). CONCLUSIONS: Laparoscopic surgery for colorectal cancer is technically
      more demanding in Japanese obese II patients than in nonobese or obese I
      patients. Special care is required because of the increased risk of developing
      postoperative complications.

PMID- 22146163
TI  - Colon cancer in the splenic flexure: comparison of short-term outcomes of
      laparoscopic and open colectomy.
AB  - BACKGROUND: Laparoscopic surgery for colon cancer in the splenic flexure (SF
      cancer) is technically demanding and has not been evaluated in randomized
      clinical trials. This study aimed to evaluate the safety and feasibility of
      laparoscopic surgery for SF cancer. METHODS: Thirty-three patients undergoing
      laparoscopic surgery for SF cancer (LAC group) were retrospectively compared with
      22 patients undergoing open surgery for SF cancer (OC group) between April 2003
      and June 2010. RESULTS: Left hemicolectomy was the most performed procedure in
      both groups (79% vs. 82%). Median operating time was significantly longer (209
      vs. 178 min) and estimated blood loss was significantly lower (15 vs. 113 mL) in
      the LAC group than in the OC group. Conversion to open surgery was needed for 1
      (3%) patient because of bleeding near the pancreas. Tumor stage was more advanced
      in the OC group than in the LAC group, but N stages were similar between groups.
      The median number of lymph nodes harvested was significantly higher in the LAC
      group than in the OC group (16 vs. 12). The rate of postoperative complications
      was significantly lower in the LAC group than in the OC group (6% vs. 36%). Time
      to flatus (1 vs. 3 d), time to liquid diet (2 vs. 5 d), and hospital stay (12 vs.
      16 d) were significantly shorter in the LAC group than in the OC group.
      CONCLUSIONS: Laparoscopic surgery for SF cancer is feasible.

PMID- 22146164
TI  - Analysis of the tumor color patterns of early esophageal cancer using an
      autofluorescence imaging video endoscopy.
AB  - BACKGROUND: Using a novel autofluorescence imaging video (AFI) endoscopy system,
      early esophageal cancers (EECs) appeared purple or brown in green background.
      However, the factors associated with these color patterns remain unraveled. The
      aims of this study were to classify the AFI color patterns of EECs and to
      investigate the correlation between the color patterns and clinicopathologic
      features of EECs. PATIENTS: From April 2008 to April 2010, 32 patients with 42
      EECs who underwent endoscopic submucosal dissection at the Nagasaki University
      Hospital were enrolled in this study. They consisted of 25 men and 7 women, with
      the mean age of 64.7 years old (range, 52 to 82 y). METHODS: With AFI endoscopy,
      we classified 2 color patters in EECs into purple in green patterns (P in G) and
      brown with purple dots in green patterns (BP in G), and we assessed the
      association with clinicopathologic factors. These factors included tumor
      morphology, location, size, histologic depth of invasion, and histologic
      lymphatic and vessel permeations. RESULTS: The color patterns of EECs were
      classified into 2 groups: purple in green patterns (P in G) (14%) and brown with
      purple dots in green patterns (BP in G) (86%). Univariate analysis revealed that
      only macroscopic type was associated with the EECs color pattern. CONCLUSIONS:
      This study revealed the association of AFI color patterns with clinicopathologic
      factors of EECs. Recognition of the color patterns in AFI images might be useful
      for the detections and diagnosis of EECs as one of the new endoscopic modalities.

PMID- 22146165
TI  - Comparative analysis of station-specific lymph node yield in laparoscopic and
      open distal gastrectomy for early gastric cancer.
AB  - BACKGROUND: Randomized trials and cohort studies show that laparoscopic distal
      gastrectomy (LDG) achieves similar oncological results to open distal gastrectomy
      (ODG). However, studies have consistently demonstrated lower lymph node yield
      (LNY) for laparoscopic lymphadenectomy. Analysis of station-specific LNY may be
      useful in evaluating the reasons behind this difference. OBJECTIVES: Comparison
      of station-specific LNY, surgical, and oncological outcomes between LDG and ODG
      for early gastric cancer. METHODS: Patients who underwent R0 distal gastrectomy
      with histologically confirmed early gastric cancer were eligible for the study.
      All consecutive cases of LDG since the beginning of our experience with
      laparoscopic gastrectomy and synchronous cases of ODG with R0 resection were
      included in the study. Demographic, operative, histopathologic, and follow-up
      data were recorded in all patients. RESULTS: A total of 259 cases of LDG and 95
      cases of ODG were performed between 2000 and 2009. Patients undergoing LDG had
      longer operations but less bleeding (P<0.05). Postoperative complications were
      similar in both groups. The preoperatively planned extent of lymphadenectomy was
      D1 (stations 1, 3, 4sb, 4d, 5, 6, and 7), D1+ (D1with stations 8a and 9), or D2
      (D1+ with stations 11p and 12a). During surgery, dissection of stations 3, 4d, 5,
      6, and 7 was performed in all cases of LDG and ODG. Dissection of stations 1,
      4sb, 8a, 9, 11p, and 12a was performed more frequently during ODG than during
      LDG. Consequently, the total LNY was 26.71 and 31.43 for LDG and ODG,
      respectively. Station-specific LNY was significantly lower for LDG than for ODG
      in the common hepatic artery nodes only (P<0.05). The mean follow-up was 43.6
      months. Lymph node metastases, metastatic-to-resected lymph node ratio,
      recurrence, and cancer-related deaths were similar for LDG and ODG. CONCLUSIONS:
      LDG was associated with less extensive lymph node dissection compared with ODG.
      Station-specific LNY was similar in all nodal stations except for the common
      hepatic artery nodes. In our experience, laparoscopic sub-D2 lymphadenectomy was
      adequate in the context of early gastric cancer and represents the future of
      gastric cancer resection in Japan.

PMID- 22146166
TI  - Dual-ports laparoscopy-assisted distal gastrectomy compared with conventional
      laparoscopy-assisted distal gastrectomy.
AB  - PURPOSE: We performed laparoscopic gastrectomy using an umbilical port in
      addition with one other port (dual-ports laparoscopy-assisted distal gastrectomy,
      DP-LADG) since December 2009. We describe a retrospective study to evaluate the
      possibility of DP-LADG compared with conventional LADG (C-LADG). METHODS: The
      indication for DP-LADG was preoperative clinical Stage IA gastric cancer. We
      compared 20 patients who underwent DP-LADG with 24 patients of clinical Stage IA
      patients who underwent C-LADG. RESULTS: The mean operation time was significantly
      longer for DP-LADG (250.5 min) than for C-LADG (197.5 min); however, the mean
      operation time for the last 5 patients undergoing DP-LADG (209 +/- 31.1 min) was
      almost the same as that for C-LADG. There were no significant differences between
      DP-LADG and C-LADG in terms of blood loss, number of lymph nodes dissected, rates
      of conversion to open surgery, postoperative complications, and length of
      postoperative hospital stay. CONCLUSIONS: DP-LADG is technically feasible.

PMID- 22146167
TI  - The effects of 3 different intra-abdominal pressures on the thromboelastographic
      profile during laparoscopic cholecystectomy.
AB  - OBJECTIVE: The aim was to determine the influence of the pneumoperitoneum at 10,
      13, and 16 mm Hg on thromboelastograph (TEG) in laparoscopic cholecystectomy.
      METHODS: Sixty patients were randomly allocated to 3 groups. The abdomen was
      insufflated with carbon dioxide to 10 mm Hg (group 1), 13 mm Hg (group 2), and 16
      mm Hg (group 3) intra-abdominal pressures. We evaluated changes in the TEG values
      [reaction time (R), maximum amplitude (MA), alpha-angle, K time] preoperatively,
      intraoperatively, and postoperatively. RESULTS: In the postoperative 24th hour,
      the R-value was significantly lower in group 3 than that in group 1 and group 2
      (P<0.05). We found increased values of MA intraoperative 30th minute and
      postoperative 24th hour in group 3 with respect to group 1 (P<0.05) and
      postoperative 24th hour, and the MA value in group 3 was significantly higher
      than those of group 2 (P<0.05). In group 3, the alpha-angle was significantly
      higher than that of group 1 and group 2 at intraoperative 30th minute and
      postoperative 24th hour (P<0.05). In postoperative 24th hour, the K-value was
      significantly lower in group 3 than in group 2 and group 1 (P<0.05). CONCLUSIONS:
      Laparoscopy with pneumoperitoneum at pressures of 10 and 13 mm Hg did not alter
      the TEG values and low intra-abdominal pressure must be used for peritoneal
      insufflation.

PMID- 22146168
TI  - Conventional laparoscopic adrenalectomy versus laparoscopic adrenalectomy through
      mono port.
AB  - A standard procedure for single-port laparoscopic adrenal surgery has not been
      established. We retrospectively investigated intraoperative and postoperative
      outcomes after laparoscopic adrenalectomy through mono port (LAMP) and
      conventional laparoscopic adrenalectomy to assess the feasibility of LAMP.
      Between March 2008 and December 2009, 22 patients underwent adrenalectomy at the
      Department of Surgery, Kangbuk Samsung Hospital. Twelve patients underwent
      conventional laparoscopic adrenalectomy and 10 patients underwent LAMP. The same
      surgeon performed all the surgeries. The 2 procedures were compared in terms of
      tumor size, operating time, time to resumption of a soft diet, length of hospital
      day, and postoperative complications. The 2 groups were similar in terms of tumor
      size (30.08 vs. 32.50 mm, P=0.796), mean operating time (112.9 vs. 127 min,
      P=0.316), time to resumption of a soft diet (1.25 vs. 1.30 d, P=0.805), and
      length of hospital day (4.08 vs. 4.50 d, P=0.447). Despite 1 patient in the LAMP
      group experiencing ipsilateral pleural effusion as a postoperative complication,
      this parameter was similar for the 2 groups (P=0.195). Perioperative mortality,
      blood transfusion, and conversion to open surgery did not occur. Perioperative
      outcomes for LAMP were similar to those for conventional laparoscopic
      adrenalectomy. LAMP appears to be a feasible option for adrenalectomy.

PMID- 22146169
TI  - Laparoscopic antireflux surgery with polyglactin (vicryl) mesh.
AB  - BACKGROUND: There is no debate that laparoscopic fundoplication has become the
      standard procedure for surgical management of gastroesophageal reflux disease.
      However, there is still no consensus on whether to use prosthetic material
      routinely and on the preferred kind of prosthetic material. The aim of this study
      was to evaluate polyglactin mesh and polypropylene mesh use in laparoscopic
      antireflux surgery (LARS) with particular regard to symptomatic relief, patient
      satisfaction, and complications. METHODS: This prospective randomized study
      included 75 patients who underwent LARS with polypropylene mesh prosthesis and 75
      patients who underwent LARS with polyglactin (vicryl) mesh prosthesis between
      January 2005 and January 2010. Preoperative and postoperative assessments of
      symptomatic and functional outcomes of patients were recorded. Outcome data
      analyzed included length of hospitalization, operative time, complications, and
      recurrence. RESULTS: Laparoscopic repair of hiatal crura with a polyglactin mesh
      resulted in good symptomatic and clinical outcomes similar to that of
      polypropylene mesh. The recurrence rate with the use of polyglactin mesh is
      comparable to that of synthetic or biological materials reported in the
      literature. CONCLUSIONS: Closure of hiatal crura with a prosthetic polyglactin
      (vicryl) mesh at LARS is an effective and safe procedure.

PMID- 22146170
TI  - Endoscopic sphincterotomy for common bile duct stones during laparoscopic
      cholecystectomy is safe and effective.
AB  - Management strategy for common bile duct (CBD) stones is controversial with
      several treatment options if stones in the CBD are recognized intraoperatively.
      The aim of this study was to report our experience with same-session combined
      endoscopic-laparoscopic treatment of gallbladder and CBD stones. We
      retrospectively evaluated 31 patients with cholecystolithiasis and CBD stones
      undergoing same-session combined endoscopic retrograde cholangiopancreatography
      (ERCP) with sphincterotomy and endoscopic stone extraction and laparoscopic
      cholecystectomy. Same-session ERCP and sphincterotomy were performed in all
      patients, and stone extraction was successfully performed in 29 patients (93%)
      with 2 failures (7%) due to impacted stones. In 8 patients (26%), the
      laparoscopic procedure was converted to open cholecystectomy because of dense
      adhesions or unclear anatomy. Two patients (7%) developed mild pancreatitis
      postoperatively and no other morbidity or mortality. In conclusion, same-session
      ERCP with stone extraction and laparoscopic cholecystectomy seems to be a safe
      and effective treatment strategy for CBD stones.

PMID- 22146171
TI  - Direct upper kidney pole access and early ligation of renal pedicle significantly
      facilitates transperitoneal laparoscopic nephrectomy procedures: Tunc technique.
AB  - We modified our technique in transperitoneal laparoscopic nephrectomies and
      compared its results with the classical technique. Classical technique was
      performed in 85 cases (group 1). Modified technique (n=98) included direct kidney
      upper pole access and early ligation of renal pedicle (group 2). No significant
      differences were detected regarding mean patient age, intraoperative blood loss,
      and duration of hospital stay between the 2 groups (P>0.05). Mean operation time
      was 64.9 +/- 19.3 and 28.2 +/- 7.7 minutes, respectively in groups 1 and 2
      (P=0.001). Mean operation time including right nephrectomies was 68.7 +/- 23.4
      and 24.2 +/- 6.3 minutes, respectively in groups 1 and 2 (P=0.001). Mean
      operation time including left nephrectomies was 63.8 +/- 17.1 and 33.6 +/- 5.1
      minutes, respectively in groups 1 and 2 (P=0.001). Similarly, mean operation time
      was significantly shorter in group 2 when analysis was performed among right and
      left radical and simple nephrectomies between the 2 groups (P=0.001). Direct
      upper kidney pole access and early ligation of renal pedicle seems to be
      significantly facilitating transperitoneal laparoscopic nephrectomy procedures.

PMID- 22146172
TI  - Unsupervised virtual reality training may not increase laparoscopic suturing
      skills.
AB  - BACKGROUND: Numerous studies have been published showing the effect of virtual
      reality simulator training on laparoscopic skills. Most of these studies have not
      focused on simulator training in a nonsupervised setting. OBJECTIVE: The aim of
      the study was to investigate whether virtual reality simulation training alone
      increases basic laparoscopic suturing skills. DESIGN: After an instructional
      video, a pretest involving suturing of bovine intestines was performed. The
      participants were then randomised into 2 groups. The study group received 4
      training sessions on a virtual reality simulator whereas the other group received
      no training. After the training period, the suturing test was repeated. SETTING:
      Central Hospital, Norway. PARTICIPANTS: Twenty-six internship candidates, of
      which 22 completed the study. RESULTS: Both groups increased their suturing
      skills significantly when comparing the results of the 2 tests; however, no
      difference was found in the increase of skills between the groups. CONCLUSIONS:
      This study indicates that virtual reality simulator training alone may not
      increase laparoscopic suturing skills.

PMID- 22146173
TI  - Initial experience of single-incision laparoscopic right colectomy with minimum
      umbilical access.

PMID- 22146174
TI  - Hand-assisted laparoscopic partial splenectomy using an endopath monopolar
      sealer.
AB  - A partial splenectomy is a good way to prevent postsplenectomy infections by
      preservation of the immune role of the spleen for select patients. Although a
      laparoscopic total splenectomy is a safe and feasible treatment modality, the
      laparoscopic approach has not been generally adopted for a partial splenectomy
      because of technical difficulties. The hand-assisted technique provides an
      excellent means to explore, to retract safely, and to apply immediate hemostasis
      in solid organ resection. The hand-assisted laparoscopic partial splenectomy
      using an endopath monopolar sealer (Salient EndoSH2.0 Monopolar Sealer) was
      performed successfully. The segmental arteries and veins were isolated and
      divided using a tactile feedback. Splenic parenchyma was dissected and sealed
      using an endopath monopolar sealer. The surgical field was almost bloodless
      during the parenchymal transection and the transection time was around 15
      minutes. The hand-assisted laparoscopic approach allows partial splenectomy as a
      safe and bloodless surgery for select patients.

PMID- 22146175
TI  - Laparoendoscopic single-site adjustable gastric banding: technical
      considerations.
AB  - PURPOSE: Recently, laparoendoscopic single-site surgery (LESS) has been proposed
      to minimize the invasiveness of laparoscopic surgery. We present our standardized
      technique of LESS adjustable gastric banding. METHODS: Data of 25 patients who
      underwent LESS adjustable gastric banding between March 2009 and January 2010 was
      reviewed retrospectively. All procedures were performed with multiple low-profile
      trocars through a single incision using conventional laparoscopic instruments.
      RESULTS: Mean operative time was 78 minutes. Mean blood loss was 8 mL and the
      median stay was 0.3 days (range, 0.1 to 3 d). No mortality was noted and there
      was 1 reoperation in the perioperative period due to stoma obstruction.
      CONCLUSIONS: LESS adjustable gastric banding with traditional rigid instruments
      is feasible and safe but requires working with limited triangulation. Short-term
      outcomes are promising but long-term follow-up is needed in weighing in the
      potential benefits to the patient against the technical challenges that arise
      with this technique.

PMID- 22146176
TI  - Advanced staging laparoscopy using single-incision approach for unresectable
      pancreatic cancer.
AB  - PURPOSE: As laparoscopy can detect imaging-occult metastatic lesions, it has been
      validated as a means of improving the assessment of tumor staging. Although
      controversy exists as to whether the procedure should be used routinely or
      selectively in pancreatic cancer patients, patients considered for treatment
      protocols for locally unresectable pancreatic cancer should be staged
      laparoscopically before initiation of therapy. We evaluate the feasibility and
      safety of advanced staging laparoscopy including peritoneal lavage cytology,
      laparoscopic ultrasound sonography (LUS), and LUS-guided biopsy through a single
      incision for locally advanced pancreatic cancer. METHODS: Staging laparoscopy was
      performed in 44 patients with pancreatic cancer for deciding on treatment
      strategy. Our procedures included extensive peritoneal lavage of abdominal cavity
      for cytology, LUS for small metastasis detection, and tissue sample excision
      including LUS-guided biopsy. Eleven consecutive patients were treated with a
      single-incision staging laparoscopy approach (SI-SL group). The clinical
      parameters were compared between the SI-SL group and the multi-incision staging
      laparoscopy group (multi-incision group). RESULTS: The mean operating time was
      longer and bleeding volume was less in the SI-SL group, although the differences
      were without statistical significance. The conversion rates to laparotomy were 9%
      in the SI-SL group and 30% in the multi-incision group. There were no severe
      postoperative complications. LUS-guided biopsy revealed malignancy for 3 patients
      in the SI-SL group. CONCLUSIONS: Advanced SI-SL is a feasible and safe
      alternative to the multi-incision approach for pancreatic cancer.

PMID- 22146177
TI  - Laparoendoscopic single-site cholecystectomy: using a gelport device.
AB  - INTRODUCTION: Laparoendoscopic single-site (LESS) surgery has emerged as a viable
      and widely applicable minimally invasive technique. Presented here are the steps
      necessary to perform LESS cholecystectomy using a readily available gelport
      device. METHODS: To perform LESS cholecystectomy we make a 2 cm incision through
      the umbilicus until the fascia is identified. The fascia is opened 2 cm and a
      wound protector is inserted. Through the gelport we insert a 5 mm trocar with a
      balloon tip for the insufflation and three 5 mm trocars as working ports. Three
      of the trocars are placed in the lower third in a semilunar configuration before
      mounting the gelport onto the wound protector. A fourth trocar can then be placed
      at the superior aspect of the gelport. Intra-abdominal visualization is obtained
      with an articulating 5 mm laparoscope. RESULTS: At our institution 19 patients
      have undergone LESS cholecystectomy out of 20 attempts (5% conversion rate), with
      the first 15 patients undergoing a single skin incision, multifascial incision
      approach and the last 5 done using a gelport device and single fascial incision.
      One patient in the multifascial group required conversion to a dual incision
      laparoscopic cholecytectomy due to cystic duct bleeding. Overall, procedures
      averaged 81 minutes (range, 43 to 181 min), the average length of stay was <1 day
      (range, 0 to 2 d). To date, 1 patient developed a wound infection that responded
      to oral antibiosis (5% overall complication rate), and no hernias have developed
      with a mean follow-up of 9 months (range, 3 to 12 mo). CONCLUSIONS: The gelport
      may allow for the widespread use of this exciting technology even in
      nonspecialized centers because of the familiarity of minimally invasive surgeons
      with this device. The elasticity of this device seems to facilitate the use of 4
      trocars, thus, replicating the "critical view" of the structures of the triangle
      of Calot seen in standard multi-incision laparoscopic cholecystectomy.

PMID- 22146178
TI  - Transanal endoscopic microsurgery via TriPort Access System with no general
      anesthesia and without sphincter damage.
AB  - The aim of this study was to develop a less-invasive transanal endoscopic
      microsurgery (TEM) operative technique that could be applied in severely ill
      patients. Modified technique of TEM operation with use of the TriPort Access
      System in place of the operative rectoscope was designed. Harmonic scalpel and
      regular laparoscopic instruments were used. Resection of the rectal stump tumor
      was performed. A 71-year-old male patient with recurrent adenocarcinoma T2N0M0 in
      rectal stump and ASA 4 was operated using presented technique with good outcome.
      Total operating time was 25 minutes. There were no adverse events during or after
      the procedure. Patient was fully mobilized directly after the procedure. Proposed
      technique can be performed in severely ill patients as it avoids anal sphincter
      divulsion and therefore general anesthesia. Standard laparoscopic instruments can
      be used at no extra cost and no need for additional skills.

PMID- 22146179
TI  - Successful endoscopic clipping in the early treatment of spontaneous esophageal
      perforation.
AB  - Barogenic esophageal injury or Boerhaave syndrome is an esophageal perforation
      entailing very high mortality and morbidity. Endoscopic techniques have been
      introduced in the treatment of various types of esophageal perforation. This
      report describes the first patient who underwent a successful endoscopic clipping
      involving sealing of a transpleural esophageal rupture within 24 hours of the
      onset of symptoms.

PMID- 22146180
TI  - Endoscopic removal of impacted magnetic foreign bodies in the gastroesophageal
      junction.
AB  - Ingestion of foreign bodies is common in gastroenterology practice. Most of them
      are spontaneously passed through gastrointestinal tract. However, ingestion of
      multiple magnets can cause serious complications, because magnets attract each
      other and they hold the gastrointestinal wall. Here, we describe a patient who
      ingested multiple magnets that attracted each other between distal esophagus, and
      a part of them was impacted into the esophageal wall. In general, impacted
      magnetic foreign bodies should be removed by surgical intervention because of a
      high perforation risk. But, in this case, we used an insulated-tip knife for
      endoscopic submucosal dissection technique to make an incision to expose the
      impacted magnetic foreign bodies, and removed them successfully without surgery.
      With this report, we hope to encourage gastroenterologists to consider this new
      technique as one of procedures for difficult cases, including impacted foreign
      bodies.

PMID- 22146181
TI  - Hemoperitoneum caused by a ruptured GIST located in the posterior gastric wall
      managed by endoscopic diagnosis and laparoscopic treatment: case report and
      literature review.
AB  - A case of hemoperitoneum caused by a ruptured gastrointestinal stromal tumor
      (GIST) of the posterior gastric wall is presented. An otherwise healthy 81-year
      old man presented with abdominal pain/tenderness and anemia (hemoglobin: 7.4
      g/dL). Computed tomography scan showed hemoperitoneum and a gastric mass of
      uncertain nature. As the patient was hemodynamically stable, a mini-invasive
      approach was decided. Esophagogastroscopy revealed an umbilicated mass of the
      posterior gastric wall, therefore allowing for a correct preoperative diagnosis
      of GIST and its appropriate treatment by laparoscopic atypical gastrectomy.
      Laparoscopically, a longitudinal resection of gastric fundus including the tumor
      was performed in a sleeve gastrectomy fashion, 25 minutes after the induction of
      pneumoperitoneum. The outcome was uneventful. Pathologic examination confirmed a
      benign 4 * 3-cm gastric GIST with <1 mitosis per 50 high power field, staining
      positive for CD117 (C-KIT) and negative for S-100 protein and smooth muscle
      actin. To our knowledge, it is the first case of a successful laparoscopic
      resection of an endoscopically diagnosed gastric GIST in an emergency setting.
      Hemoperitoneum is a rare, potentially severe complication of GIST. As bleeding is
      rarely severe, most patients may benefit from a mini-invasive approach, even if
      the tumor is located in the posterior gastric wall.

PMID- 22146182
TI  - Nephroscope in the management of recurrent pyogenic cholangitis.
AB  - Several minimally invasive procedures have been successfully used for removal of
      stones from the hepatobiliary system. We describe an innovative interventional
      radiologic procedure using rigid urologic instruments within the hepatobiliary
      system. Stones within the hepatic and bile ducts in a patient with recurrent
      pyogenic cholangitis were removed by a technique resembling percutaneous
      nephrolithotomy for renal stones.

PMID- 22146183
TI  - Endoscopic-assisted colopexy and push percutaneous colostomy in the transverse
      colon for refractory chronic intestinal pseudo-obstruction.
AB  - Percutaneous endoscopic colostomy (PEC), using the classic pull-through technique
      in the ascending or the descending colon, has been proven useful to treat chronic
      intestinal pseudo-obstruction. We report the case of a high-surgical risk 70-year
      old male with refractory chronic intestinal pseudo-obstruction, in whom the
      ascending colon could not be reached due to tortuous left dolichocolon.
      Endoscopic-assisted colopexy and push colostomy in the proximal transverse colon
      was decided accordingly. Colopexy was performed under direct endoscopic vision in
      the proximal transverse colon using 3 preloaded T-fasteners surrounding the
      intended stoma site. The stoma tract was created with an introducer needle,
      allowing the advance of the 24 Fr 4-sleeve dilator over a guidewire. Afterwards,
      the dilator was removed and the peel-away sheath was left in place. Over the
      guidewire, a 20-Fr gastrostomy tube was advanced into the colon lumen through the
      covering, which was finally removed. The patient recovered uneventfully, despite
      postprocedure pneumoperitoneum, which was related to the technique. He died a
      month later due to unrelated comorbidities, without further abdominal complaints
      after discharge. This is the first report of PEC both using a push technique, and
      the first report in a different location than the ascending or the descending
      colon. We believe this novel push technique may be feasible for PEC, avoiding the
      need of reinsertion in patients with difficult colonoscopy.

PMID- 22146184
TI  - Laparoscopic resection of a retroperitoneal schwannoma.
AB  - Schwannomas or neurilemomas are rare, benign tumors that originate from the
      neural sheath. A 54-year-old man presented with left flank discomfort and lumbar
      pain for 6 months. A computed tomographic scan confirmed the existence of a 12 *
      9 cm heterogeneous retroperitoneal mass adherent to the left psoas muscle that
      displaced the left kidney anteriorly. Total laparoscopic removal of the tumor was
      performed and pathologic examination revealed a benign schwannoma.

PMID- 22146185
TI  - Laparoscopic umbilical hernia repair in the presence of extensive paraumbilical
      collateral veins:  a case report.
AB  - A patient with an umbilical hernia presenting with collateral veins in the
      abdominal wall and umbilicus is a case that every hernia surgeon has to deal with
      occasionally. Several underlying diseases have been described to provoke
      collateral veins in the abdominal wall. However, the treatment strategy should be
      uniform. We herein report a case of a successful laparoscopic umbilical hernia
      repair in a patient with collateral veins in the abdominal wall and umbilicus. A
      63-year-old man was referred to the surgical outpatient clinic with a large
      symptomatic umbilical hernia and collateral veins in the abdominal wall,
      secondary to an occlusion of both common iliac veins. Because of collateral veins
      in the umbilicus and the size of the hernial defect, he was offered laparoscopic
      hernia repair without compromising these veins. Because of the extensive
      abdominal wall collaterals, duplex sonography vein mapping was performed
      preoperatively to mark a safe collateral-free area for trocar introduction. The
      defect was repaired by mesh prosthesis.

PMID- 22146186
TI  - Laparoscopic pancreas-preserving total duodenectomy for familial adenomatous
      polyposis.
AB  - Patients with duodenal polyps associated with familial adenomatous polyposis
      (FAP) have a considerable risk of developing duodenal carcinoma. Prophylactic
      resection of the duodenum for Spigelman stage III disease is the treatment of
      choice to prevent progression to cancer. Pancreaticoduodenectomy and pancreas
      preserving total duodenectomy (PPTD) are the techniques that have been described
      for the surgical treatment of duodenal polyposis. We report the first case of
      laparoscopic PPTD in a patient with previous total colectomy for FAP and
      Spigelman stage III duodenal polyposis. A laparoscopic total dissection of the
      duodenum was carried out and the restoration was achieved performing pancreatico
      biliary-jejunostomy and gastrojejunostomy. The postoperative period was
      uneventful. Laparoscopic PPTD can be performed safely in selected cases for the
      management of FAP.

PMID- 22146187
TI  - Laparoscopic resection of ancient schwannoma embedded in the psoas muscle.
AB  - Schwannoma is a tumor originating from the Schwann cell of the peripheral nerve
      sheath. The diagnosis of schwannoma is based on histologic analysis of surgically
      excised sample. Retroperitoneal ancient schwannoma, a variant of schwannoma, is
      rarely observed in clinical practice. We report the case of a 46-year-old man
      with a retroperitoneal tumor embedded in the psoas muscle, which was treated by
      laparoscopic resection. The operative result was good, and pathologic analysis
      revealed a 5.5 * 4.5 cm ancient schwannoma.

PMID- 22146188
TI  - Laparoscopic adrenalectomy for a rare 14-cm adrenal schwannoma.
AB  - Laparoscopic surgery for adrenal tumors is the gold standard for benign tumors;
      however, its role for adrenal cancer, metastases, and large suspicious lesions
      remains controversial. This aspect becomes clinically more important as larger
      incidentaloma are being detected with increasing frequency. Here, we discuss a
      rare case of a giant 14-cm adrenal schwannoma, which presented as an
      incidentaloma and was excised laparoscopically. Epidemiology, histology, and
      surgical treatment options were reviewed. An abdominal computerized tomography
      scan of a 30-year-old female weighing 130 kg revealed a large left adrenal mass.
      Preoperative biochemical and endocrine workup confirmed that it was
      nonfunctioning. The patient had a laparoscopic adrenalectomy without
      complication. The nodular tumor measured 145 * 100 * 80 cm in size and weighed
      312 g. Histopathology showed myxoid areas and spindle cells arranged in a
      palisading manner. Mitoses were not observed. Tumor cells were
      immunohistochemically strongly positive for S-100, but negative for CD117,
      desmin, and muscle-specific actin. There was no evidence of malignancy. The
      diagnosis was of a benign schwannoma. Adrenal schwannoma is an extremely rare
      entity and can grow considerably in size. So far, this is the largest adrenal
      schwannoma reported in literature. In agreement with a growing number of
      publications, laparoscopic adrenalectomy can also be used for potentially
      malignant tumors larger than 10 cm in diameter provided the tumor does not
      infiltrate into other organs, conversion to open surgery is carefully considered,
      and resection occurs within the anatomic planes, thus ensuring the intactness of
      the tumor capsule.

PMID- 22146189
TI  - Laparoscopic Roux-en-Y duodenojejunal bypass for superior mesenteric artery
      syndrome: case reports and review of the literature.
AB  - INTRODUCTION: Superior mesenteric artery syndrome is a clearly defined and
      uncommon medical condition. Surgical intervention is needed for failed long-term
      medical management. MATERIAL AND METHODS: We report a series of 3 cases, a 17
      year-old woman, a 23-year-old man, and a 50-year-old woman that were successfully
      treated by Roux-en-Y duodenojejunal bypass using a laparoscopic approach.
      TECHNIQUE: A 5-trocar laparoscopic approach was used for the surgery. A 75 cm
      long Roux limb was used in all cases. RESULTS: The postoperative period was
      unremarkable and symptoms of obstruction subsided in all 3 cases. CONCLUSIONS:
      Laparoscopic duodenojejunal bypass seems to be a feasible and safe treatment
      option for superior mesenteric artery syndrome.

PMID- 22146190
TI  - Counting what counts.
AB  - This month's issue of JOSPT contains a bibliometric analysis of the publishing
      history of the Journal of Orthopaedic & Sports Physical Therapy. The results
      provide an opportunity to reflect on trends at JOSPT and, more generally, in the
      evidence base of orthopaedic and sports physical therapy practice. Results of the
      bibliometric review by Coronado and colleagues are encouraging for JOSPT and the
      profession of physical therapy as a whole. The results indicate an increase in
      the publication of research articles involving symptomatic subjects, with fewer
      narrative and nonsystematic review papers. The results also raise an interesting
      issue about whether we have a sufficient number of randomized controlled trials
      in our literature and to what extent our future progress should be based on the
      publication of more randomized trials.

PMID- 22146191
TI  - Cortical spreading ischemia in the absence of proximal vasospasm after aneurysmal
      subarachnoid hemorrhage: evidence for a dual mechanism of delayed cerebral
      ischemia.
AB  - There are longstanding inconsistencies in the evidence thought to link vasospasm
      in the major branches of the Circle of Willis with delayed cerebral ischemia and
      poor outcome from aneurysmal subarachnoid hemorrhage (aSAH). The demonstrations,
      first in the laboratory, and more recently in patients with aSAH, of cortical
      spreading ischemia based on an abnormal response of the cerebral microcirculation
      to spreading depolarization offer an additional possible mechanism for delayed
      ischemia. That such events can occur in the substantial absence of proximal
      vasospasm is compatible with this concept, but the preliminary evidence needs
      support from more extensive studies.

PMID- 22146192
TI  - Release of mitochondrial apoptogenic factors and cell death are mediated by CK2
      and NADPH oxidase.
AB  - Activation of the NADPH oxidase subunit, NOX2, and increased oxidative stress are
      associated with neuronal death after cerebral ischemia and reperfusion.
      Inhibition of NOX2 by casein kinase 2 (CK2) leads to neuronal survival, but the
      mechanism is unknown. In this study, we show that in copper/zinc-superoxide
      dismutase transgenic (SOD1 Tg) mice, degradation of CK2alpha and CK2alpha' and
      dephosphorylation of CK2beta against oxidative stress were markedly reduced
      compared with wild-type (WT) mice that underwent middle cerebral artery
      occlusion. Inhibition of CK2 pharmacologically or by ischemic reperfusion
      facilitated accumulation of poly(ADP-ribose) polymers, the translocation of
      apoptosis-inducing factor (AIF), and cytochrome c release from mitochondria after
      ischemic injury. The eventual enhancement of CK2 inhibition under ischemic injury
      strongly increased 8-hydroxy-2'-deoxyguanosine and phosphorylation of H2A.X.
      Furthermore, CK2 inhibition by tetrabromocinnamic acid (TBCA) in SOD1 Tg and gp91
      knockout (KO) mice after ischemia reperfusion induced less release of AIF and
      cytochrome c than in TBCA-treated WT mice. Inhibition of CK2 in gp91 KO mice
      subjected to ischemia reperfusion did not increase brain infarction compared with
      TBCA-treated WT mice. These results strongly suggest that NOX2 activation
      releases reactive oxygen species after CK2 inhibition, triggering release of
      apoptogenic factors from mitochondria and inducing DNA damage after ischemic
      brain injury.

PMID- 22146193
TI  - Delayed cerebral ischemia and spreading depolarization in absence of angiographic
      vasospasm after subarachnoid hemorrhage.
AB  - It has been hypothesized that vasospasm is the prime mechanism of delayed
      cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH).
      Recently, it was found that clusters of spreading depolarizations (SDs) are
      associated with DCI. Surgical placement of nicardipine prolonged-release implants
      (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we
      tested whether SDs and DCI are abolished when vasospasm is reduced or abolished
      by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal
      intracranial vessels. The SDs were recorded using a subdural electrode strip.
      Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs
      were recorded in 10 of 13 patients (77%). Digital subtraction angiography
      revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate
      vasospasm in the remaining. Five patients developed DCI associated with clusters
      of SD despite the absence of angiographic vasospasm in three of those patients.
      The number of SDs correlated significantly with the development of DCI. This may
      explain why reduction of angiographic vasospasm alone has not been sufficient to
      improve outcome in some clinical studies.

PMID- 22146194
TI  - Experimental subarachnoid hemorrhage causes early and long-lasting microarterial
      constriction and microthrombosis: an in-vivo microscopy study.
AB  - Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is characterized by
      a severe, cerebral perfusion pressure (CPP)-independent reduction in cerebral
      blood flow suggesting alterations on the level of cerebral microvessels.
      Therefore, we aimed to use in-vivo imaging to investigate the cerebral
      microcirculation after experimental SAH. Subarachnoid hemorrhage was induced in
      C57/BL6 mice by endovascular perforation. Pial arterioles and venules (10 to 80
      MUm diameter) were examined using in-vivo fluorescence microscopy, 3, 6, and 72
      hours after SAH. Venular diameter or flow was not affected by SAH, while >70% of
      arterioles constricted by 22% to 33% up to 3 days after hemorrhage (P<0.05 versus
      sham). The smaller the investigated arterioles, the more pronounced the
      constriction (r(2)=0.92, P<0.04). Approximately 30% of constricted arterioles
      were occluded by microthrombi and the frequency of arteriolar microthrombosis
      correlated with the degree of constriction (r(2)=0.93, P<0.03). The current study
      demonstrates that SAH induces microarterial constrictions and microthrombosis in
      vivo. These findings may explain the early CPP-independent decrease in cerebral
      blood flow after SAH and may therefore serve as novel targets for the treatment
      of early perfusion deficits after SAH.

PMID- 22146195
TI  - Navigated total hip arthroplasty using a 3-D freehand ultrasound system:
      technical note and preliminary results.
AB  - Ultrasound-navigated cementless total hip arthroplasty (THA) was performed in 10
      consecutive patients with primary osteoarthritis of the hip between August 2008
      and October 2009 (M:F, 6:4; median age, 61 years; age range, 30-86 years). The
      pelvic orientation was defined by preoperative digitization and registration of
      bony landmarks. Cup inclination and anteversion were documented for each patient
      intraoperatively (epidigitized vs ultrasound-assessed landmarks). The median
      difference between the palpated and ultrasound anterior pelvic plane was 8
      degrees  (range, 4 degrees -18 degrees ) for pelvic tilt (rotation around the
      transversal axis), 1 degrees  (range, -3 degrees  to 2 degrees ) for rotation
      around the longitudinal axis, and 0.25 degrees  (range, -2.0 degrees  to 5.0
      degrees ) for rotation around the sagittal axis. The median difference in cup
      orientation resulting from pelvic tilt error was 6 degrees  (range, 3 degrees -13
      degrees ) for anteversion and 3 degrees  (range, -1 degrees  to 5 degrees ) for
      inclination. There were no intra- or postoperative complications. The measured
      width of soft tissue layer anterior to the pelvic symphysis correlated
      significantly with the measured difference in cup inclination and anteversion.
      One centimeter of soft tissue anterior to the symphysis resulted in a median 2
      degrees  (range, 1.75 degrees -2.3 degrees ) difference in pelvic tilt.
      Ultrasound-assisted navigation in THA is a promising technology able to eliminate
      systematic errors in anterior pelvic plane orientation, in contrast to
      conventionally navigated THA using percutaneous palpation of landmarks or THA
      without navigational support.

PMID- 22146196
TI  - Pelvic osteotomy techniques and comparative effects on biomechanics of the hip: a
      kinematic study.
AB  - Dysplasia of the hip is characterized by malpositioning of the proximal femur in
      a shallow acetabulum, providing deficient femoral head coverage. This abnormal
      relationship leads to altered biomechanics of the hip joint, as predicted by
      measurement of kinematic parameters such as increased load over reduced
      acetabular weight-bearing area, leading to increased joint contact stresses,
      which subsequently results in secondary osteoarthrosis, pain, and disability. To
      prevent these sequelae, particularly in children and younger adults, various
      osteotomies have been performed with varying degrees of success. The goal of this
      study was to devise a simple and reproducible laboratory method to perform a
      kinematic analysis of the individual and comparative effects of 5 commonly
      performed pelvic osteotomy techniques: Chiari pelvic osteotomy, Salter innominate
      bone wedge osteotomy, Steel triple pelvic osteotomy, Tonnis triple pelvic
      osteotomy, and Ganz periacetabular pelvic osteotomy. The aim was to determine
      which of the osteotomy techniques caused greater correction in most of the
      kinematic parameters used to estimate changes in the biomechanics of the hip
      joint. Our hypothesis was that pelvic osteotomies such as Chiari and Salter
      produced favorable changes and were relatively easily reproducible, but that more
      biomechanical correction in all planes would be achieved by the relatively more
      complex triple innominate bone and Ganz osteotomy.

PMID- 22146198
TI  - Primary pyomyositis of the pelvis in children: a retrospective review of 8 cases.
AB  - Primary pyomyositis of the pelvic musculature is a condition rarely seen in
      temperate climates, although its frequency has been increasing in the United
      States. The condition should be considered in the initial differential diagnosis
      of an adolescent presenting with fever, difficulty ambulating, and hip pain. This
      is a retrospective review of 8 cases of primary pelvic pyomyositis in patients
      aged 18 years or younger who were treated at the Children's Medical Center in
      Augusta, Georgia. The site of infection was the obturator internus in the
      majority of the cases (5). The site was the gluteus, iliopsoas, and iliacus in 1
      case each. Four patients who were diagnosed early responded to intravenous
      antibiotics with no need for further intervention. Two patients required incision
      and drainage of an abscess combined with antibiotics. Two patients had prolonged
      hospital courses requiring intensive unit care and mechanical ventilation. Blood
      cultures were positive in 87.5% of patients, and all patients presented with
      elevated acute phase reactants. One of the most difficult diagnostic aspects of
      presentation is an inconclusive symptom profile. It is noteworthy that patients
      with pelvic pyomyositis may present with limited range of motion in a specific
      plane (the motion placing the infected muscle on stretch) vs global limited range
      of motion of the joint as is commonly seen in septic arthritis. Early diagnosis
      is essential to prevent systemic illness and complications associated with this
      condition. Magnetic resonance imaging with gadolinium is helpful to diagnose and
      guide treatment.

PMID- 22146197
TI  - Percutaneous limited internal fixation combined with external fixation to treat
      open pelvic fractures concomitant with perineal lacerations.
AB  - External fixation combined with colostomy is a traditional management of the
      pelvic fractures associated with perineal lacerations. However, malunion and
      dysfunction caused by malreduction and loss of reduction are common. One-stage
      definitive fixation without soft tissue harassment is requisite for the
      treatment. The purpose of this study was to assess the outcome of 1-stage
      definitive fixation by combining percutaneous limited internal fixation and
      external fixation in the treatment of pelvic fractures with perineal lacerations.
      Eighteen adults with high-energy unstable pelvic ring fractures associated with
      perineal lacerations were admitted between June 2003 and December 2010. Mean
      follow-up was 28 months. After wound closure and colostomy, 10 patients received
      external fixation and percutaneous screw fixation, and 8 patients underwent
      external fixation. Demographics, wound and fracture classification, and Injury
      Severity Score were comparable between the groups (P>.05). Initial reduction
      quality was comparable between the groups (P=.14), but the loss of reduction
      during follow-up was more significant in the external fixation group (P=.004).
      Combined fixation achieved better functional results than external fixation
      (P=.02). There were 2 cases of superficial wound infection in each group (P=1.0).
      By combining debridement, wound closure, colostomy, percutaneous limited internal
      fixation, and external fixation, we improved pelvic fracture recovery while
      reducing the risk of infection. One-stage definitive fixation is a better choice
      than external fixation in the treatment of open pelvic fracture concomitant with
      perineal wound.

PMID- 22146199
TI  - Perioperative morbidity and mortality of 2-team simultaneous bilateral total knee
      arthroplasty.
AB  - Total knee arthroplasty (TKA) has a well-established track record for relieving
      pain associated with arthritis of the knee joint. The total rate of bilateral TKA
      has doubled over the past 2 decades, and the rate in women has tripled over that
      same time period. In patients with bilateral knee arthritis, a decision must be
      made whether to operate at 2 different settings (staged), a single setting with 1
      surgeon (sequential simultaneous), or a single setting with 2 surgeons (2-team
      simultaneous). The purpose of this study was to examine the perioperative
      morbidity and mortality of 2-team simultaneous bilateral TKA. Two hundred twenty
      seven consecutive 2-team simultaneous bilateral TKA and 216 consecutive
      unilateral TKA patients were reviewed. Major (deep infection, death,
      cerebrovascular accident, myocardial infarction, pulmonary embolism, revision
      within the 1-year follow-up) and minor (all other) complications were compared.
      No deaths occurred, and the major and minor complication rates were not
      statistically significantly different between the 2 groups, but a trend toward
      higher rates of both major and minor complications existed in the bilateral TKA
      group. Two-team simultaneous bilateral TKA offers the potential benefits of
      decreased overall recovery time, decreased overall cost, decreased number of
      anesthetic administrations, and simultaneous correction of significant deformity.
      It remains an appropriate option in select patients.

PMID- 22146200
TI  - Relative risk of different operations for medial compartment osteoarthritis of
      the knee.
AB  - The relative risk of total knee arthroplasty (TKA), high tibial osteotomy (HTO),
      and medial unicompartment (UKA) replacement for medial compartment arthritis is
      presented. Risk is defined as the product of the probability of an event
      occurring and its consequence. To define consequence, 2 related scales of impact
      (1 systemic and 1 local) are suggested. The probability of a complication is
      derived from the incidence as found in the published literature and expressed as
      a decimal of 1. The cumulative risk is expressed as the sum of the risks of all
      individual complications. The overall impact of specific comorbidities has been
      calculated when their influence on the incidence of a particular complication is
      known. Of the 3 operations, TKA has the highest cumulative risk of systemic
      complications and HTO is the most likely to produce local technical problems. UKA
      is the safest of the procedures. The relative risk of TKA:HTO:UKA is
      1.00:1.01:0.31. For TKA, the greatest additional risk is morbid obesity, which
      increases overall risk by 31% by virtue of a 7.8-fold increase in infection rate.
      Cardiorespiratory disease, diabetes mellitus, smoking, and cirrhosis of the liver
      increase cumulative risk by 20%, 17%, and 17%, respectively.The authors conclude
      that a quantitative assessment of operative risk is possible and useful. However,
      it depends on the availability of reliable complication incidence data.

PMID- 22146201
TI  - Flexion contracture following primary total knee arthroplasty: risk factors and
      outcomes.
AB  - Function and satisfaction after total knee arthroplasty (TKA) are partially
      linked to postoperative range of motion (ROM). Fixed flexion contracture is a
      recognized complication of TKA that reduces ROM and is a source of morbidity for
      patients. This study aimed to identify preoperative risk factors for developing
      fixed flexion contracture following TKA and to quantify the effect of fixed
      flexion contracture on outcomes (Oxford knee score 12-60 and patient
      satisfaction) at 2 years. Pre-, intra-, and postoperative data for 811 TKAs were
      retrospectively reviewed. At 2 years postoperatively, the incidence of fixed
      flexion contracture was 3.6%. Men were 2.6 times more likely than women to have
      fixed flexion contracture (P=.012), and patients with preimplant fixed flexion
      contracture were 2.3 times more likely than those without to have fixed flexion
      contracture (P=.028). Increasing age was associated with an increased rate of
      fixed flexion contracture (P=.02). Body mass index was not a risk factor
      (P=.968). Incidence of fixed flexion contracture for those undergoing computer
      navigated TKA was 3.9% compared with 3.4% for those having conventional surgery
      (P=.711). Patients with fixed flexion contracture had poorer outcomes with a
      median [interquartile range] Oxford Knee Score of 25 [15] compared with 20 [11]
      for those without (P=.003) and lower patient satisfaction (P=.036). These results
      support existing literature for incidence of fixed flexion contracture after TKA,
      risk factors, and outcomes, indicating that these figures can be extrapolated to
      a wide population. They also clarify a previously contentious point by excluding
      body mass index as a risk factor.

PMID- 22146202
TI  - Differing prosthetic alignment and femoral component sizing between 2 computer
      assisted CT-free navigation systems in TKA.
AB  - We adopted a new computed tomography (CT)-free navigation system and noticed
      that, compared with our previous experience using a different type of CT-free
      navigation system that led to oversized and extended femoral component implanted
      compared with the conventional implantation, the femoral components were
      similarly implanted to the conventional method. The purpose of our study was to
      compare alignment and sizing with these 2 image-free systems and determine
      whether the method to determine the knee center could explain these differences
      in femoral component size and flexion of the component. Thirty posterior
      stabilized total knee prostheses were implanted using the OrthoPilot CT-free
      navigation system (B. Braun-Aesculap, Tuttlingen, Germany). Postoperative coronal
      and sagittal long leg radiographs were retrospectively compared with those of a
      control group of 30 matched-paired total knee prostheses previously implanted
      using the VectorVision CT-free navigation system (Depuy-BrainLAB, Heimstetten,
      Germany). Sagittal alignment of the femoral component in the VectorVision group
      showed a significantly extended position compared with that in the OrthoPilot
      group. In addition, the size of the selected femoral component in the Vector
      Vision group was significantly larger than that in the OrthoPilot group. This
      discrepancy may be explained by the differences in the determined knee center,
      which influenced the postoperative implantation. When surgeons select a
      navigation system, the characteristics of each system should be taken into
      consideration.

PMID- 22146203
TI  - Biomechanical evaluation of tibial eminence fractures using suture fixation.
AB  - This study evaluates the initial fixation strength of tibial eminence fracture
      repair using 1, 2, 3, and 4 sutures to determine the optimal number of sutures
      required to adequately secure the avulsed fragment to the tibia. Sixteen
      skeletally immature porcine knees were stripped of all soft tissues, isolating
      the femur-anterior cruciate ligament (ACL)-tibia complex. Type III tibial
      eminence fractures were simulated in the specimens, and each specimen was
      randomly assigned to a repair group using 1, 2, 3, or 4 #2 FiberWire sutures
      (Arthrex, Inc, Naples, Florida). Initial fixation strength of the repair was
      measured by single cycle pull to failure testing using a materials testing
      machine (Instron, Norwood, Massachusetts). The mean ultimate failure force during
      anterior tibial translation was 389+/-128, 627+/-66, 703+/-77, and 802+/-29 N for
      1, 2, 3, and 4 sutures, respectively. The lower limit of the 95% confidence
      interval was >500 N (estimated force of native ACL during activities of daily
      living) for each group with >=2 sutures. In this study, at least 2 high-strength
      sutures were needed for tibial eminence fracture repairs to withstand potential
      forces seen across the ACL in the postoperative period. Suture fixation of tibial
      eminence fractures is a reproducible method requiring a minimum of 2 high
      strength polyester sutures to resist forces seen during early rehabilitation.

PMID- 22146204
TI  - Modular megaprosthesis in metastatic bone disease of the femur.
AB  - The treatment of bone metastases is frequently palliative, aiming to achieve
      satisfactory pain control and to prevent or treat pathological fractures. For
      lesions involving the femur, internal fixation frequently fails; therefore,
      prosthetic reconstruction may be the optimal choice for treatment. This article
      retrospectively reviews our experience with femoral bone metastases between 1999
      and 2008. A series of 22 patients (14 men and 8 women; mean age, 61.8 years) with
      femoral bone metastases were treated with resection and modular megaprosthetic
      reconstruction. Bipolar hip prostheses were used in 19 patients, intercalary
      prostheses were used in 2 patients, and total knee replacement was used in 1
      patient. Oncologic outcome was evaluated, and functional outcomes were obtained
      by the Musculoskeletal Tumor Society (MSTS) score, which assigns numerical values
      (0-5) for each of 5 parameters, excluding emotional status. A numerical score
      (maximum 25 points) and percent rating was calculated. Six-month survival was
      86.4%, 1-year survival was 54.2%, and 2-year survival was 37.1%. Three patients
      were unable to ambulate due to acute paraplegia with spinal metastases at the
      perioperative period. Excluding these 3 patients, average MSTS score was 62.3%.
      The MSTS score in patients surviving >12 months was 70.8% compared with a score
      of 46.4% in those living <12 months (P<.05). Complications included 2
      dislocations. Megaprosthetic reconstruction provides for optimal treatment of
      femoral metastatic disease in patients with a prognosis of >12 months with
      satisfactory functional outcomes based on lower complications.

PMID- 22146205
TI  - Bone morphogenetic protein-2 compared to autologous iliac crest bone graft in the
      treatment of long bone nonunion.
AB  - This retrospective study investigated the effect of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) mixed with cancellous allograft on fracture
      healing compared to iliac crest autograft in the treatment of long bone nonunion.
      Eighty-nine patients with 93 established long bone nonunions treated between
      January 2002 and June 2004 at a single academic Level I trauma center were
      evaluated. Patients with clinical and radiographic evidence of failed fracture
      union underwent nonunion debridement, revision of fixation, and implantation at
      the nonunion site of either rhBMP-2 or the standard treatment autologous iliac
      crest bone graft. Union rate, operative time, estimated intraoperative blood
      loss, hospital length of stay, and postoperative infections were recorded.
      Nineteen nonunions received rhBMP-2 on a specialized carrier matrix (an
      absorbable collagen sponge) mixed with cancellous allograft, and 74 nonunions
      were treated with autologous iliac crest bone graft. There was no statistical
      difference in the rate of healing between treatment groups (68.4% vs 85.1%,
      respectively; P=.09). Incidence of postoperative infection was 16.2% after
      autologous iliac crest bone graft and 5.3% after rhBMP-2/absorbable collagen
      sponge (P=.22). Iliac crest autograft was associated with longer operative
      procedures (257.9+/-93.0 vs 168.9+/-86.5 minutes; P=.0007) and greater
      intraoperative blood loss (554.6+/-447.8 vs 331.6+/-357.2 mL; P=.01). These
      outcomes suggest that rhBMP-2 may provide a suitable alternative to autologous
      iliac bone graft, with the possible advantages of shorter operative time and
      reduced intraoperative blood loss, and may be considered as part of the
      orthopedic surgeon's treatment options.

PMID- 22146206
TI  - Lower-limb amputations in patients with diabetes mellitus.
AB  - It is estimated that approximately 23.6 million people in the United States have
      diabetes mellitus. With adequate control of this disease and appropriate foot
      care and basic surveillance, many patients can lead active and healthy
      lifestyles. However, some patients experience complications associated with
      poorly controlled glucose levels, including lower-extremity ulcerations and
      infections. When conservative measures have failed in treating these conditions,
      a lower-extremity amputation is an option for patients seeking to gain maximal
      functional recovery. A complete preoperative workup includes assessment of
      healing potential and preoperative ambulatory status, control or optimization of
      comorbidities when possible, and determination of amputation level using modern
      diagnostic modalities. Once the decision to proceed with an amputation has been
      made, it is important to choose an appropriate level of amputation and practice
      sound surgical technique. This article describes the preoperative evaluation and
      operative techniques involved in performing amputations on diabetic patients and
      reviews the current literature on the most common lower-extremity amputations
      performed in the care of infections in the feet of patients with diabetes
      mellitus.

PMID- 22146207
TI  - Atypical lipomatous tumors/well-differentiated liposarcomas: clinical outcome of
      67 patients.
AB  - Atypical lipomatous tumors/well-differentiated liposarcomas are low-grade
      malignant mesenchymal neoplasms with high propensity to local recurrence and
      potential to dedifferentiate to higher grades over time. However, the published
      risks of local recurrence and dedifferentiation vary, and no unified treatment
      and follow-up plan has been accepted. We performed a study to evaluate the long
      term clinical behavior and proper treatment and follow-up strategy for these
      tumors. We retrospectively reviewed the files of 101 patients treated between
      1990 and 2008 with the diagnosis of atypical lipomatous tumors/well
      differentiated liposarcomas. For 67 of these patients, complete data and 2-year
      minimum follow-up were available and were included in the study; 47 patients
      (group A) had primary surgical treatment at our institution and 20 patients
      (group B) were referred after >=1 local recurrences. Mean follow-up was 81 months
      (range, 24-229 months). The local recurrence rate of primary atypical lipomatous
      tumors/well-differentiated liposarcomas was 10.6% (5/47 group A patients). The
      local re-recurrence rate of the recurrent atypical lipomatous tumors/well
      differentiated liposarcomas was 52% (13/67 group A and B patients). Recurrences
      developed as late as 140 months after diagnosis and treatment. The rate of
      dedifferentiation at recurrences was 4% (1/25 group A and B patients with
      recurrent tumors). No patients developed metastases. Atypical lipomatous
      tumors/well-differentiated liposarcomas are associated with an increased rate of
      local re-recurrence and low risk of dedifferentiation at recurrences. Long-term
      follow-up is recommended for early diagnosis and treatment of local recurrences.

PMID- 22146208
TI  - Total condylar unipolar expandable prosthesis for proximal tibia malignant bone
      tumors in early childhood.
AB  - Wide resection and reconstruction of tumors of the proximal tibia in the
      pediatric population are challenging procedures. The use of hinged, expandable
      prostheses may cause early closure of the distal femoral growth plate, which may
      increase the risk of limb discrepancy already present in this population. Between
      1991 and 2001, 2 girls and 1 boy, aged 6, 6, and 4 years, respectively, were
      diagnosed with osteosarcoma of the proximal tibia and treated with wide resection
      and reconstruction with a condylar unipolar expandable tibial prosthesis. A press
      fitted technique was used for component insertion. All patients received
      neoadjuvant and adjuvant chemotherapy. Radiographic and functional follow-up took
      place at least once a year for a minimum of 4 years. Adequate pain control, limb
      length equality, and acceptable function were obtained in all patients. One
      patient presented with significant range of motion reduction (0 degrees - 30
      degrees ) in the affected knee. Limb lengthening was performed as needed to
      maintain balanced limb length. All patients had a good Musculoskeletal Tumor
      Society category score. No complications occurred in terms of component loosening
      or infection. One patient died shortly after 4-year follow-up because of
      doxorubicin-induced leukemia. Currently used hinged, expandable prostheses can
      jeopardize the unaffected distal femoral growth plate. This article describes a
      technique of reconstruction that spares the distal femoral growth plate. Adequate
      limb length can be expected with acceptable functional outcome. However, it is
      imperative to keep in perspective the expectations of the physician, the
      physician's team, the patient, and the patient's family.

PMID- 22146209
TI  - New computed radiography processing condition for whole-spine radiography.
AB  - Computed radiography (CR) has many advantages compared with conventional
      radiographs, especially in image processing. Although CR is being used in chest
      radiography and mammography, it has not been applied to spine imaging. The
      purposes of this study were to formulate a set of new CR processing parameters
      and to test whether the resultant whole-spine radiographs visualized the spine
      more clearly than conventional images. This study included 29 patients who
      underwent whole-spine radiographs. We used 3 image processing methods to improve
      the clarity of whole-spine radiographs: gradation processing, dynamic range
      control processing, and multi-objective frequency processing. Radiograph
      definition was evaluated using vertebrae sampled from each region of the whole
      spine, specifically C4, C7, T8, T12, and L3; evaluation of the lateral view also
      included the sacral spine and femoral head. Image definition was assessed using a
      3-point grading system. The conventional and processed CR images (both frontal
      and lateral views) were evaluated by 5 spine surgeons. In all spinal regions on
      both frontal and lateral views, the processed images showed statistically
      significantly better clarity than the corresponding conventional images,
      especially at T12, L3, the sacral spine, and the femoral head on the lateral
      view. Our set of new CR processing parameters can improve the clarity of whole
      spine radiographs compared with conventional images. The greatest advantage of
      image processing was that it enabled clear depiction of the thoracolumbar
      junction, lumbar vertebrae, sacrum, and femoral head in the lateral view.

PMID- 22146210
TI  - Spinal posterior movement after posterior cervical decompression surgery:
      clinical findings and factors affecting postoperative functional recovery.
AB  - This study investigated the posterior movement of the spinal cord after posterior
      decompression surgery and evaluated factors affecting postoperative functional
      recovery in patients with cervical spondylotic myelopathy (CSM). Thirty-two
      patients with CSM underwent posterior decompression from C3 to C7 through
      laminectomy (n=12) and single, open-door laminoplasty (n=20). There were no
      significant differences between laminectomy and laminoplasty in degree of spinal
      posterior movement, recovery rate, and curvature index. Japanese Orthopedic
      Association (JOA) scores improved from preoperative (10.63+/-1.77; range, 7-14)
      to 3-months postoperative (13.57+/-1.50; range, 11-16) (n=32, P<.05) and from
      preoperative (10.24+/-1.87; range, 7-14) to 6-months postoperative (14.16+/-1.54;
      range, 12-16) (n=21) (P<.05). C5 palsy was observed in 1 (3.1%) patient. The
      vertebral body-to-spinal cord distances significantly increased after operations,
      with the greatest posterior movement at C5 and the least posterior movement at C3
      and C7. However, the difference in the degree of the spinal movement of C3 to C7
      was not statistically significant (P>.05). Furthermore, no correlation was found
      between the magnitude of spinal posterior movement and the curvature index. In
      addition, the magnitude of posterior movement and age were not correlated with
      the postoperative JOA improvement, but the preoperative JOA scores were. Our
      study shows that both laminectomy and laminoplasty can produce a similar degree
      of posterior movement of the spinal cord. Cervical lordosis is not associated
      with the posterior movement of the cord. The preoperative JOA scores, but not
      posterior movement of the cord and age, are important determinants for
      postoperative outcome.

PMID- 22146211
TI  - Factors affecting interest in orthopedics among female medical students: a
      prospective analysis.
AB  - The field of orthopedics has a limited ability to recruit high-quality female
      applicants. The purpose of this study was to determine whether early exposure to
      the field affects a woman's decision to pursue orthopedics. We performed a
      prospective, nonrandomized cohort study between academic years 2005 and 2009 and
      compared interest in orthopedic surgery among female (n=271) and male (n=71)
      medical students at 2 urban teaching institutions. Elective lectures and
      orthopedic literature were distributed via e-mail to the study participants.
      These materials included articles published in the medical literature, materials
      produced and distributed by the American Academy of Orthopaedic Surgeons, and Web
      sites providing educational materials. The primary outcome was the likelihood of
      application for orthopedic residency. We studied the influence of demographics,
      exposure, and attitudes on interest in pursuing an orthopedic career. Men had a
      significantly higher baseline level of interest in orthopedic surgery than women
      (P=.005). Younger age (P<.001) and personal (P<.001), independent (P<.001), and
      school (P=.023) exposures to orthopedics were significantly related to interest
      among women. At final follow-up, total personal exposures (P=.003) and total
      independent exposures (P<.001) in the form of our literature and lectures were
      correlated with final interest in women. Female interest was decreased by the
      long hours, physical demands, and predominantly male nature of the field. Early
      exposure to orthopedic educational resources may be useful in generating female
      interest. Perceptions and attitudes regarding orthopedic surgery must to be
      changed to attract the best and brightest minds, regardless of sex.

PMID- 22146212
TI  - Nontraumatic, spontaneous dislocation of polyethylene tibial insert 1 year after
      TKA.
AB  - The authors report a case of nontraumatic, spontaneous dislocation of a
      polyethylene insert detected 1 year after total knee arthroplasty. The patient
      demonstrated initial improvement and returned to work 4 months postoperatively.
      At 6 months postoperatively, the patient developed pain and a clunking sensation
      with motion; however, he denied any traumatic precipitating events. An
      arthroscopic procedure revealed arthrofibrotic formations but no signs of locking
      mechanism failure. At 12 months postoperatively, the patient developed sudden
      instability, and radiographs demonstrated an anteriorly dislodged insert.
      Revision surgery was performed, and the insert was removed. The insert showed
      some signs of fatigue due to the locking mechanism. We postulated that repetitive
      flexion produced an anterior superior force leading to failure of the locking
      mechanism.

PMID- 22146213
TI  - Cold saline lavage for removal of incarcerated porous ingrowth stems.
AB  - A patient with a history of total knee arthroplasty and 5 subsequent revisions
      presented with pain. His preoperative construct consisted of a revision implant
      with porous in-growth stem extensions. He was indicated for revision surgery for
      a painful implant with progressive arthrofibrosis. The surgery proceeded
      uneventfully until we were unable to loosen the proximal portion of the ingrown
      femoral stem. After the distal femur was removed, a trephine was used to break
      the bone ingrowth from the distal portion of the stem. Flexible osteotomes were
      used to loosen the bone-prosthetic interface, but they were unable to penetrate
      deep enough, and they eventually bent under the applied loads. Nonflexible
      osteotomes were also used without success, and we were still unable to remove the
      stem from within the femur. Slap hammers, vice grips, and other devices were used
      to try to remove the stem, but attempts were unsuccessful. We hung a 3-liter bag
      of ice-cold (4  degrees C) saline and ran all 3 liters of saline, under gravity
      pressure, retrograde down the femoral shaft in an attempt to contract the metal
      and allow for the removal of the stem. We then attached a stem extension screw to
      the incarcerated femoral stem and were able to remove it with minimal effort
      using a back-slap device. We inspected the prosthesis and found no abnormalities
      of the stem to explain its incarceration and no iatrogenic perforations in the
      femur. This case demonstrates a useful technique that should be kept in a
      revision surgeon's armamentarium for the removal of incarcerated porous ingrowth
      stems.

PMID- 22146214
TI  - Bisphosphonate fractures as a cause of painful total hip arthroplasty.
AB  - Osteoporotic fractures pose a significant health concern for postmenopausal
      women. Bisphosphonate therapy has been shown to decrease the risk of these
      fractures. The bisphosphonate alendronate was approved by the US Food and Drug
      Administration for use in the United States in 1995, but questions have recently
      arisen concerning low-energy subtrochanteric femur fractures sustained by chronic
      users. Although no definitive association or causality between bisphosphonates
      and these fractures has been established, numerous cautionary reports exist
      concerning the duration of use and safety of alendronate in osteoporotic
      patients. This article reports 3 occurrences of bisphosphonate-associated
      atypical femur fractures as an etiology of periprosthetic hip pain in the total
      hip arthroplasty (THA) patient. These fractures are particularly concerning
      because these patients are often not advised to protect their weight bearing
      simply due to a painful THA and may sustain a catastrophic failure if not
      followed closely. Several theories have been suggested concerning the
      pathophysiology of atypical low-energy subtrochanteric fractures following
      bisphosphonate use. Each patient described in this article carried a diagnosis of
      rheumatoid arthritis and underwent chronic medical therapy; each patient
      experienced a delay in the diagnosis and onset of therapy due to low suspicion
      for bisphosphonate-associated fracture. This problem may become more common in
      the clinical setting; therefore, one must be vigilant and aware of this etiology
      of periprosthetic hip pain.

PMID- 22146215
TI  - Retained broken outflow cannula recovered 6 years post-knee arthroscopy.
AB  - One of the most common procedures performed in orthopedics is knee arthroscopy,
      and a variety of complications are found with this procedure. One of the most
      avoidable complications is that of retained instruments. This article describes
      the case of a patient in the private practice orthopedic setting who returned 6
      years after a knee arthroscopic procedure reporting acute onset pain. It was
      discovered that a broken piece of the outflow cannula that had been used in the
      arthroscopy was present in her knee joint. This particular case highlights the
      importance of diligence within the operating room. A variety of instrument
      failures have been discussed in the literature, and these instrument failures
      must be considered when discharging patients from surgical procedures. Surgeons
      and operating room staff must be meticulous in inspection of surgical instruments
      both before and after the procedure. In our case, the instrument that had broken
      during the arthroscopic procedure fractured in such a way that it was not
      immediately evident. Had the staff noticed the change in the instrument either
      after the initial procedure or before the subsequent procedures in which the
      instrument was used, the patient could have been notified about the incident
      sooner.

PMID- 22146216
TI  - Surgical treatment for permanent dislocation of the patella in adults.
AB  - Permanent dislocation of the patella in adults is a rare condition that presents
      with complete irreducible lateral dislocation of the patella, combined with
      secondary changes, such as valgus deformity and leg-length discrepancy. Because
      these secondary changes cannot heal spontaneously after skeletal maturation if
      left untreated, the patients frequently possess pathology not limited to the knee
      joint and extending to the whole lower extremity, such as malalignment or leg
      length discrepancy, that can develop into osteoarthritis of the knee. However, to
      our knowledge, few surgeons advocate the significance of correcting the
      malalignment in treating adult patients. We treated a 34-year-old woman with
      permanent dislocation of the patella in a 2-stage surgery, consisting of first
      stage correction of valgus deformity and limb shortening using a Ilizarov
      external fixator and second-stage realignment of the dislocated patella over the
      trochlea. A follow-up examination conducted 3 years after the second operation
      revealed plantigrade gait with normal alignment of the lower extremity without
      limping and medial thrust. The patella was tracking centrally in the
      patellofemoral groove. Radiographs showed a neutral mechanical axis of the lower
      extremity, no evidence of patellar subluxation, and no deteriorating
      osteoarthritic changes at the tibiofemoral joint. This case highlights the
      importance of correcting secondary changes, such as valgus deformity and leg
      length discrepancy, to reduce the risk of future osteoarthrosis and postoperative
      dislocation, especially when these deformities are substantial.

PMID- 22146217
TI  - Multifocal infection of mycobacterium other than tuberculosis mimicking a soft
      tissue tumor of the extremity.
AB  - Mycobacterium other than tuberculosis infections rarely develop in healthy
      individuals, but direct inoculation such as contaminated acupuncture can cause
      mycobacteriosis even in an immunocompetent host. A 56-year-old woman gradually
      developed pain on the anterior aspect of the left knee and the distal thigh after
      hiking without trauma. She received acupuncture for 3 consecutive days on the
      bilateral knees at the suprapatellar and infrapopliteal areas. After acupuncture,
      mild localized heat and painful swelling developed around the knees bilaterally.
      Magnetic resonance imaging (MRI) demonstrated soft tissue masses with a lobulated
      contour at the prefemoral fat between the suprapatellar pouch and the distal
      femur and at the proximal tibia behind the knee joint capsule. Fibromatosis,
      pigmented villonodular synovitis, and soft tissue sarcoma were considered. On
      pathologic examination, multiple granulomas with lymphoplasmatic infiltration
      were evident, and acid-fast bacteria staining revealed acid-fast bacilli. A
      mycobacterial culture confirmed Mycobacterium other than tuberculosis infection,
      and a polymerase chain reaction-fragment length polymorphism assay identified the
      isolates as Mycobacterium abscessus. After treatment with appropriate
      antibiotics, the patient had no evidence of disease and reported no pain during
      activities of daily living. Acupuncture is growing in prominence in Europe and
      the United States, and the number of reports on complications increases with its
      widespread use. Although the risk to an individual patient is difficult to
      determine, acupuncture may cause serious complications in patients with
      coagulopathy, heart valve disease, and immune deficiency. In addition, direct
      inoculation such as contaminated acupuncture can cause mycobacteriosis even in an
      immunocompetent host.

PMID- 22146218
TI  - Intraosseous ganglion with impending fracture of the glenoid.
AB  - Intraosseous ganglia are benign cystic and often multiloculated lesions located
      in the subchondral bone. Only 13 cases around the shoulder have been described in
      the literature. These lesions are often asymptomatic, but, in cases located close
      to neurovascular structures or articular surfaces, they can be symptomatic,
      causing pain, neurologic dysfunction, or articular fractures. This article
      reports the clinical, radiographic, and pathological findings of a 34-year-old
      man reporting shoulder pain during heavy working activities. At physical
      examination, his left shoulder showed complete active and passive range of motion
      but was painful in external rotation and extension. Tests for the evaluation of
      the rotator cuff were all negative. The anterior apprehension test provoked pain.
      The Constant-Murley score was 59 points. Radiographs, computed tomography (CT)
      scan, and magnetic resonance arthrography showed an elliptical-shaped osteolytic
      area in the anteroinferior portion of the glenoid extending to the anteroinferior
      glenoid margin. Leakage of the intra-articular contrast medium showed that the
      cyst had eroded the articular surface and was about to cause an intra-articular
      fracture of the glenoid. The patient was operated on with the suspicion of an
      intraosseous ganglion. The cyst was curetted carefully and packed with autologous
      bone from the proximal tibia and artificial bone chips. At 1-year follow-up, the
      patient was completely asymptomatic and reported no pain during his working
      activities. Physical examination was negative. Radiographs and CT scan showed a
      cystic lesion in the anteroinferior margin of the glenoid that was partially
      filled by bone.

PMID- 22146219
TI  - Bilateral Achilles tendon enlargement.
AB  - Cerebrotendinous xanthomatosis is a rare, autosomal-recessive, lipid-storage
      disease with accumulation of cholestanol in most tissues, particularly within the
      Achilles tendons. It has been characterized both clinically and biochemically,
      and recently from the molecular biological aspect as well. Juvenile cataract,
      childhood diarrhea, mental retardation, cerebellar ataxia, and tendon xanthomas
      are the most prominent features of this disease. Bilateral symmetrical firm
      masses of Achilles tendons may be the first symptom the patient recognizes
      because it can jeopardize his or her ability to walk. However, the treatment
      strategies for tendon tumors vary. In a recent case, we diagnosed the disease
      properly, according to the clinical manifestations and the radiological and
      laboratory examinations. The genetic mutation was characterized by analyzing
      sterol 27-hydroxylase from the patient's family (located on nucleotide 599) and
      led to a nonsense mutation. It is a unique type of mutation that has never been
      reported to our knowledge. Tendon lesions are characterized by the loss of muscle
      fibers and accumulation of lipid products. To help the patient regain the
      strength of the Achilles tendon and walking abilities, a large area of tendon
      tumor was excised, followed by reconstruction with a tibialis posterior
      allograft, which is the second strongest tendon in the foot and ankle. Although
      the use of this type of graft is uncommon, the final result was satisfactory. At
      the 10-month follow-up examination, the patient could walk easily without pain.
      This case report suggests that the surgical procedure will provide an alternative
      for the repair of large-area degenerative Achilles tendons.

PMID- 22146220
TI  - Herpes zoster virus: an unusual but potentially treatable cause of sciatica and
      foot drop.
AB  - The herpes zoster virus is a rare but potential cause of acute motor weakness.
      This article describes 2 patients with drop foot secondary to an infection of
      varicella zoster who were incorrectly referred to an orthopedic clinic from their
      general practitioners. The first patient was a 74-year-old man who presented with
      weakness in the right foot and a vesicular rash. The pattern of disease supported
      the clinical diagnosis of shingles affecting the L5 motor and sensory division.
      No investigation was required, and the patient was treated with a foot drop
      splint. The second patient was a 71-year-old man who presented with right leg and
      foot weakness and a vesicular rash affecting his right buttock and posterior
      right thigh. Lumbar magnetic resonance excluded a stenotic lesion;
      electrophysiological studies supported the diagnosis of a lower motor neuron
      lesion. The patient was treated with a 1-week course of acyclovir and a foot drop
      splint. The correct diagnosis will aid in correct referral and will prompt
      management, which will potentially provide a faster and better outcome for the
      patient.

PMID- 22146221
TI  - Minimotif Miner 3.0: database expansion and significantly improved reduction of
      false-positive predictions from consensus sequences.
AB  - Minimotif Miner (MnM available at http://minimotifminer.org or
      http://mnm.engr.uconn.edu) is an online database for identifying new minimotifs
      in protein queries. Minimotifs are short contiguous peptide sequences that have a
      known function in at least one protein. Here we report the third release of the
      MnM database which has now grown 60-fold to approximately 300,000 minimotifs.
      Since short minimotifs are by their nature not very complex we also summarize a
      new set of false-positive filters and linear regression scoring that vastly
      enhance minimotif prediction accuracy on a test data set. This online database
      can be used to predict new functions in proteins and causes of disease.

PMID- 22146222
TI  - Hydrogen saline offers neuroprotection by reducing oxidative stress in a focal
      cerebral ischemia-reperfusion rat model.
AB  - Hydrogen gas is neuroprotective in cerebral ischemia animal models. In this
      study, we tested the neuroprotective effects of hydrogen saline, which is safe
      and easy to use clinically, in a rat model of middle cerebral artery occlusion
      (MCAO). Sprague-Dawley male rats weighting 250-280 g were divided into sham, MCAO
      plus hydrogen saline and MCAO groups, and subjected to 90-min ischemia followed
      by 24 h of reperfusion. Hydrogen saline was injected intraperitoneally at 1
      ml/100 g body weight. Infarct volume and brain water content were evaluated at
      different time points after reperfusion. Oxidative stress, inflammation, and
      apoptotic cell death markers were measured. Hydrogen saline significantly reduced
      the infarct volume and edema and improved the neurological function, when it was
      administered at 0, 3 and 6 h after reperfusion. Hydrogen saline decreased 8
      hydroxyl-2'-deoxyguanosine (8-OHdG), reduced malondidehyde, interleukin-1beta,
      tumor necrosis factor-alpha, and suppressed caspase 3 activity in the ischemic
      brain. These findings demonstrated hydrogen saline is neuroprotective when
      administered within 6 h after ischemia. Because hydrogen saline is safe and easy
      to use, it has clinical potentials to reduce neurological injuries.

PMID- 22146223
TI  - [Renal involvement in cancer and renal paraneoplastic syndromes].
AB  - BACKGROUND: Renal alterations in the context of neoplastic disease are relatively
      frequent manifestations but are overall poorly reported. MATERIAL AND METHODS: A
      search in the English and French literature was performed using the following key
      words: "cancer", "renal", "paraneoplastic syndrome", "glomerulopathy" and "kidney
      failure". RESULTS: The various renal manifestations can be divided into specific
      and paraneoplastic. They include paraneoplastic glomerulopathies (membranous
      glomerulonephristis being the most frequent), direct involvement of the renal
      parenchyma, hydroelectrolytic abnormalities (hypercalcemia, inappropriate
      antidiuretic hormone secretion...), retroperitoneal fibrosis, micro
      angiothrombotic disease and tumor lysis syndrome. Anticancer and symptomatic
      treatments do not guaranty complete recovery in all cases. CONCLUSION: The
      frequency and the severity of some renal manifestations associated with malignant
      hemopathies and carcinomas indicates a need for initial renal-oriented work-up
      and follow-up.

PMID- 22146224
TI  - Lurasidone: a new treatment option for schizophrenia.
AB  - Lurasidone is a novel benzoisothiazol antipsychotic that has recently been
      approved for the treatment of schizophrenia in the U.S. Like many other second
      generation antipsychotics, it has a high affinity for dopamine D(2) and serotonin
      5-HT(2A) receptors as well as a high affinity for 5-HT(7) receptors. It has
      negligible affinity for alpha(1)-adrenoceptors, histamine H(1) receptors or
      muscarinic acetylcholine M(1) receptors. It has demonstrated efficacy in short
      term trials versus placebo, two of which included an active comparator
      (olanzapine, quetiapine) assay arm. A short-term, head-to-head trial of
      lurasidone versus ziprasidone in chronic stable schizophrenia was also conducted.
      A long-term, 12-month risperidone-controlled study and open-label studies
      primarily investigated the safety and tolerability of lurasidone. Limited
      evidence of procognitive and antidepressant effects was seen although these need
      further corroboration. The incidence of extrapyramidal symptoms (excluding
      akathisia/restlessness) was greater with lurasidone (14.7%) than placebo (5.1%).
      Akathisia and somnolence were dose-related adverse events. Lurasidone appears to
      have relatively little effect on weight, plasma glucose or lipids to date. No
      evidence of QTc prolongation was seen and orthostatic hypotension was uncommon.
      Raised prolactin levels in short-term studies were dose-dependent, greater in
      females and occurred overall in 3.7 and 0.7% of lurasidone and placebo
      recipients, respectively.

PMID- 22146225
TI  - Ruxolitinib for the treatment of myelofibrosis.
AB  - Ruxolitinib is an orally available, ATP-competitive inhibitor, selective for
      tyrosine-protein kinases JAK1 and JAK2 and is the most advanced JAK1/JAK2
      inhibitor in development for the treatment of myeloproliferative neoplasms. The
      suggested mechanism of action of ruxolitinib is attenuation of cytokine signaling
      via the inhibition of JAK1 and JAK2 (wild-type or mutated forms), resulting in
      antiproliferative and proapoptotic effects. In the phase III COMFORT-I trial
      conducted in patients with myelofibrosis, ruxolitinib demonstrated durable
      reductions in splenomegaly. The proportion of patients that achieved spleen
      volume reduction >= 35% from baseline to 24 weeks was 41.9 % with ruxolitinib
      versus 0.7% with placebo (P < 0.0001), as evaluated by magnetic resonance imaging
      or computed tomography. In the phase III COMFORT-II trial, reductions in spleen
      volume >= 35% were observed in 31.9% of patients treated with ruxolitinib versus
      0% with best available therapy at week 24, and 28.5% versus 0% at week 48 (both P
      < 0.0001). Low toxicity, alleviation of constitutional symptoms, weight gain and
      improvement in general physical condition were observed with ruxolitinib
      treatment which may substantially improve quality of life in patients with
      myelofibrosis.

PMID- 22146226
TI  - Telaprevir: looking for a sustained virologic response in hepatitis C virus
      infection.
AB  - Telaprevir, a hepatitis C virus (HCV) NS3/NS4A protease inhibitor, was recently
      approved by the U.S. Food and Drug Administration for the treatment of chronic
      HCV genotype 1 infection. When given in combination with pegylated interferon and
      ribavirin, it demonstrated improved efficacy over conventional pegylated
      interferon and ribavirin therapy. Improvement in efficacy was also noted in
      African American patients who traditionally respond less well to conventional
      anti-HCV treatment. While the role of telaprevir in the management of chronic HCV
      infection remains to be fully defined, its development and licensure represents
      an important milestone in anti-HCV therapeutics.

PMID- 22146227
TI  - An update on exenatide, a novel therapeutic option for patients with type 2
      diabetes.
AB  - Exenatide, a synthetic glucagon GLP-1 receptor agonist, belongs to a new class of
      agents approved as a treatment option in patients with poorly controlled type 2
      diabetes not adequately controlled on oral antidiabetic agents. The principal
      mode of drug action includes enhanced glucose-dependent insulin secretion --the
      so called "incretin effect"-- suppression of glucagon and inhibition of
      endogenous glucose production. The potential to address these dysregulated
      pathways allows exenatide to be a valuable adjunct to existing treatment options
      for patients with poorly controlled type 2 diabetes. Clinical trials with twice
      daily exenatide have shown significant improvements in glycemic control (HbA(1c)
      reductions of 0.8-1% across studies), progressive weight loss and low incidence
      of hypoglycemia. Common side effects include nausea and vomiting which usually
      subside after a few days of therapy and do not usually necessitate withdrawal of
      the drug. In recent months, a longer-acting, once-weekly preparation of
      exenatide, which is currently approved for use in Europe, has shown promise and
      phase III studies indicate that it may be more potent and efficacious than
      existing twice-daily preparations. Meanwhile, the results from long-term studies
      to assess cardiovascular benefits with exenatide therapy are eagerly awaited.

PMID- 22146228
TI  - Multi-targeted tyrosine kinase inhibitors in clinical development: focus on XL
      184 (cabozantinib).
AB  - XL-184 (cabozantinib) is a novel, small-molecule, multitargeted receptor tyrosine
      kinase inhibitor with particular activity against hepatocyte growth factor
      receptor (tyrosine-protein kinase Met), vascular endothelial growth factor
      receptor 2 (VEGFR-2) and proto-oncogene tyrosine-protein kinase receptor Ret.
      There is ample evidence of Met, VEGFR-2 and Ret signaling in several tumor types.
      Preclinical data suggest that XL-184 has activity in tumors derived from both
      epithelial and mesenchymal origins. Phase I and II clinical studies support
      significant antitumor activity, particularly in medullary thyroid cancer and
      cancers metastatic to the bone. This review will evaluate XL-184's preclinical
      pharmacology, pharmacokinetics, drug interactions and clinical activity in phase
      I through phase III studies.

PMID- 22146229
TI  - A report from the 2011 Alzheimer's Association International Conference (July 16
      21 - Paris, France).
AB  - Alzheimer's disease (AD) is indeed a source of sadness weighing on all those who
      after sharing a full life now depend on each other for the most basic functions.
      Nevertheless, besides the dramatic impact it imposes on the life of sufferers and
      their caregivers, AD, as well as other forms of dementia that affect the elderly,
      but also younger patients, also incurs in substantial healthcare costs for
      patients, their families and others, including society at large. The progressive
      aging of the population largely depending on improved preventive and curative
      healthcare is progressively worsening the situation because of the increasing
      number of elderly people and the consequent increase in dementia sufferers.
      Effective and cost-effective treatments are thus required for reversing,
      improving or preventing these cognitive impairments. Fortunately, research has
      resulted in therapeutic opportunities that were reviewed during the 2011
      Alzheimer's Association International Conference (AAIC) in Paris, and will be
      briefly reviewed in the following report.

PMID- 22146230
TI  - Gait retraining for runners: in search of the ideal.
AB  - For physical therapists, modifying technique is not a novel concept; however, our
      motives are typically focused on symptom and injury reduction rather than purely
      performance. These specific modifications are based on minimizing tissue load,
      while still enabling successful completion of the task. Applying this same
      rationale to running, an activity in which up to 80% of participants are injured
      annually, would seem to be a good thing. Yet the idea of using gait retraining in
      patients without neurological injury/pathology is rather uncommon. However, a few
      researchers have investigated specific walking retraining strategies to reduce
      knee joint loading, with the goal of applying these techniques to individuals
      with knee osteoarthritis. This has led some to use the same concept on runners
      with patellofemoral pain, with a corresponding improvement in gait and symptoms.

PMID- 22146231
TI  - Genetic analysis of IP3 and calcium signalling pathways in C. elegans.
AB  - BACKGROUND: The nematode, Caenorhabditis elegans is an established model system
      that is particularly well suited to genetic analysis. C. elegans is easily
      manipulated and we have an in depth knowledge of many aspects of its biology.
      Thus, it is an attractive system in which to pursue integrated studies of
      signalling pathways. C. elegans has a complement of calcium signalling molecules
      similar to that of other animals. SCOPE OF REVIEW: We focus on IP3 signalling. We
      describe how forward and reverse genetic approaches, including RNAi, have
      resulted in a tool kit which enables the analysis of IP3/Ca2+ signalling
      pathways. The importance of cell and tissue specific manipulation of signalling
      pathways and the use of epistasis analysis are highlighted. We discuss how these
      tools have increased our understanding of IP3 signalling in specific
      developmental, physiological and behavioural roles. Approaches to imaging calcium
      signals in C. elegans are considered. MAJOR CONCLUSIONS: A wide selection of
      tools is available for the analysis of IP3/Ca2+ signalling in C. elegans. This
      has resulted in detailed descriptions of the function of IP3/Ca2+ signalling in
      the animal's biology. Nevertheless many questions about how IP3 signalling
      regulates specific processes remain. GENERAL SIGNIFICANCE: Many of the approaches
      described may be applied to other calcium signalling systems. C. elegans offers
      the opportunity to dissect pathways, perform integrated studies and to test the
      importance of the properties of calcium signalling molecules to whole animal
      function, thus illuminating the function of calcium signalling in animals. This
      article is part of a Special Issue entitled Biochemical, biophysical and genetic
      approaches to intracellular calcium signalling.

PMID- 22146232
TI  - Effect of insulin deprivation on metabolism and metabolism-associated gene
      transcript levels of in vitro cultured human Sertoli cells.
AB  - BACKGROUND: Sertoli cells metabolize glucose producing lactate for developing
      germ cells. As insulin regulates glucose uptake and its disturbance/insensitivity
      is associated with diabetes mellitus, we aimed to determine the effect of insulin
      deprivation in human Sertoli cell (hSC) metabolism and metabolism-associated gene
      expression. METHODS: hSC-enriched primary cultures were maintained in the
      absence/presence of insulin and metabolite variations were determined by (1)H
      NMR. mRNA expression levels of glucose transporters (GLUT1, GLUT3), lactate
      dehydrogenase (LDHA) and monocarboxylate transporter (MCT4) were determined by RT
      PCR. RESULTS: Insulin deprivation resulted in decreased lactate production and in
      decrease of glucose consumption that was completely reverted after 6h. Cells of
      both groups consumed similar amounts of glucose. In insulin-deprived cells,
      transcript levels of genes associated to lactate metabolism (LDHA and MCT4) were
      decreased. Transcript levels of genes involved in glucose uptake exhibited a
      divergent variation: GLUT3 levels were decreased while GLUT1 levels increased.
      Insulin-deprived hSCs presented: 1) altered glucose consumption and lactate
      secretion; 2) altered expression of metabolism-associated genes involved in
      lactate production and export; 3) an adaptation of glucose uptake by modulating
      the expression of GLUT1 and GLUT3. GENERAL SIGNIFICANCE: This is the first report
      regarding the effect of insulin-deprivation on hSC metabolism.

PMID- 22146234
TI  - The clinical effectiveness and cost-effectiveness of bortezomib and thalidomide
      in combination regimens with an alkylating agent and a corticosteroid for the
      first-line treatment of multiple myeloma: a systematic review and economic
      evaluation.
AB  - BACKGROUND: Multiple myeloma (MM) is the second most common haematological cancer
      in the UK. MM is not curable but can be treated with a combination of supportive
      measures and chemotherapy that aim to extend the duration and quality of
      survival. The majority of patients are not able to withstand intensive treatment,
      such as high-dose chemotherapy with autologous stem cell transplantation (SCT),
      and so they are offered single-agent or combination chemotherapy. Combination
      therapies typically include chemotherapy with an alkylating agent and a
      corticosteroid. More recently, combination therapies have incorporated drugs such
      as thalidomide (Thalidomide Celgene(r), Celgene) and bortezomib (Velcade(r),
      Janssen-Cilag). OBJECTIVE: To assess the clinical effectiveness and cost
      effectiveness of bortezomib or thalidomide in combination chemotherapy regimens
      with an alkylating agent and a corticosteroid for the first-line treatment of MM.
      DATA SOURCES: Electronic bibliographic databases, including MEDLINE, EMBASE and
      The Cochrane Library, were searched from 1999 to 2009 for English-language
      articles. Bibliographies of articles, grey literature sources and manufacturers'
      submissions were also searched. Experts in the field were asked to identify
      additional published and unpublished references. REVIEW METHODS: Titles and
      abstracts were screened for eligibility by two reviewers independently. The
      inclusion criteria specified in the protocol were applied to the full text of
      retrieved papers by one reviewer and checked independently by a second reviewer.
      Data extraction and quality assessment were undertaken by one reviewer and
      checked by a second reviewer. Differences in opinion were resolved through
      discussion at each stage. A cost-utility decision-analytic model was used to
      compare the cost-effectiveness estimates of bortezomib in combination with
      melphalan and prednisolone/prednisone (VMP), thalidomide in combination with
      cyclophosphamide and attenuated dexamethasone (CTDa), and thalidomide in
      combination with melphalan and prednisolone/prednisone (MPT) versus melphalan and
      prednisolone/prednisone (MP). RESULTS: A total of 1436 records were screened and
      40 references were retrieved for the systematic review of clinical effectiveness.
      Five randomised controlled trials (RCTs) met the inclusion criteria for the
      review: one RCT evaluated VMP, three evaluated MPT and one evaluated CTDa. The
      comparator in all of the included trials was MP. The review found that VMP and
      MPT can both be considered more clinically effective than MP for the first-line
      treatment of MM in people for whom high-dose therapy and SCT would not be
      appropriate. CTDa was more effective than MP in terms of complete response but
      data on survival outcomes did not meet the inclusion criteria. Cost-effectiveness
      analysis indicated that MPT has a greater probability of being cost-effective
      than either VMP or CTDa. LIMITATIONS: For most RCTs, details needed to judge
      study quality were incompletely reported. All studies stated that the analyses
      followed intention-to-treat principles but none adequately reported data
      censoring. Only one RCT contributed data on VMP and the published peer-reviewed
      follow-up data were immature. For MPT, overall survival data from two trials were
      eligible for inclusion but the doses of thalidomide differed between the trials
      and the treatment period was not reflective of current UK practice so the
      generalisability of the findings was uncertain. Two RCTs had a maintenance phase
      with thalidomide that did not meet the inclusion criteria so some of these
      results were not eligible for the review. Limited evidence on health-related
      quality of life (HRQoL) was provided by the single trial of VMP versus MP.
      CONCLUSIONS: Service provision is unlikely to change greatly. As uncertainties
      remain, further research is needed regarding the use of bortezomib- and
      thalidomide-containing combination regimens. Head-to-head trials of bortezomib-
      and thalidomide-containing combination regimes are required, including
      assessments of patient HRQoL in response to treatment. FUNDING: The National
      Institute for Health Research Health Technology Assessment programme.

PMID- 22146233
TI  - Resveratrol reverses monocrotaline-induced pulmonary vascular and cardiac
      dysfunction: a potential role for atrogin-1 in smooth muscle.
AB  - Arterial remodeling contributes to elevated pulmonary artery (PA) pressures and
      right ventricular hypertrophy seen in pulmonary hypertension (PH). Resveratrol, a
      sirtuin-1 (SIRT1) pathway activator, can prevent the development of PH in a
      commonly used animal model, but it is unclear whether it can reverse established
      PH pathophysiology. Furthermore, atrophic ubiquitin ligases, such as atrogin-1
      and MuRF-1, are known to be induced by SIRT1 activators but have not been
      characterized in hypertrophic vascular disease. Therefore, we hypothesized that
      monocrotaline (MCT)-induced PH would attenuate atrophy pathways in the PA while,
      conversely, SIRT1 activation (resveratrol) would reverse indices of PH and
      restore atrophic gene expression. Thus, we injected Sprague-Dawley rats with MCT
      (50 mg/kg i.p.) or saline at Day 0, and then treated with oral resveratrol or
      sildenafil from days 28-42 post-MCT injection. Oral resveratrol attenuated
      established MCT-induced PH indices, including right ventricular systolic
      pressure, right ventricular hypertrophy, and medial thickening of intrapulmonary
      arteries. Resveratrol also normalized PA atrogin-1 mRNA expression, which was
      significantly reduced by MCT. In cultured human PA smooth muscle cells (hPASMC),
      resveratrol significantly inhibited PDGF-stimulated proliferation and cellular
      hypertrophy, which was also associated with improvements in atrogin-1 levels. In
      addition, SIRT1 inhibition augmented hPASMC proliferation, as assessed by DNA
      mass, and suppressed atrogin mRNA expression. These findings demonstrate an
      inverse relationship between indices of PH and PA atrogin expression that is
      SIRT1 dependent and may reflect a novel role for SIRT1 in PASMCs opposing
      cellular hypertrophy and proliferation.

PMID- 22146235
TI  - Beneficial effects of statin treatment on coronary microvascular dysfunction and
      left ventricular remodeling in patients with acute myocardial infarction.
AB  - BACKGROUND: Statin treatment has been shown to improve coronary endothelial
      function, irrespective of lipid-lowering effects. This study's aim was to
      elucidate the effects of statin treatment on coronary microvascular dysfunction
      and left ventricular remodeling in acute myocardial infarction (AMI) patients.
      METHODS: Thirty-five patients undergoing successful reperfusion following AMI
      were assigned to a statin-treated (Group S, 16) or a non-statin-treated (Group
      NS, 19) group, according to fasting serum low-density lipoprotein-cholesterol.
      (13)N-ammonia positron emission tomography was performed to assess myocardial
      flow reserve (MFR) in the infarct area. RESULTS: Infarct sizes and lipid profiles
      during the chronic period were similar between the two groups. At 2 weeks after
      AMI onset, mean MFR in the infarct area was significantly higher in Group S than
      in Group NS (2.34 +/- 0.63 vs. 1.91 +/- 0.43, p=0.0214). At 6 months post-AMI,
      Group S had a smaller left-ventricular end-diastolic volume index (69.4 +/- 11.7
      mL/m(2) vs. 88.5 +/- 32.5 mL/m(2), p=0.0328) and higher left-ventricular ejection
      fraction (67.7 +/- 9.2% vs. 59.2 +/- 13.3%, p=0.0394) than Group NS. Serum
      asymmetric dimethylarginine was significantly increased in Group NS at 1 month
      post-AMI (0.43 +/- 0.12 MUmol/L (baseline) vs. 0.52 +/- 0.14 MUmol/L, p=0.0186),
      but unchanged in Group S. CONCLUSIONS: Statin treatment appears to beneficially
      attenuate left ventricular remodeling after AMI, which may be associated with
      restoring coronary endothelial function via endogenous nitric oxide.

PMID- 22146236
TI  - Association of endothelial and vascular smooth muscle dysfunction with
      cardiovascular risk factors, vascular complications, and subclinical carotid
      atherosclerosis in type 2 diabetic patients.
AB  - AIM: Atherosclerosis and arteriosclerosis are mainly caused by the dysfunction of
      arterial components, namely, vascular endothelial cells, smooth muscle cells, and
      the extracellular matrix. Endothelial dysfunction is well established as a
      predictive surrogate marker of cardiovascular events; however, little is known
      regarding the clinical implications of vascular smooth muscle dysfunction for
      cardiovascular disease and microangiopathy. In the present study, we aimed to
      clarify the association of arterial dysfunction with micro-/macroangiopathy and
      conventional cardiovascular risk factors in 181 type 2 diabetic patients (T2DM;
      age +/- SD, 64 +/- 10 years; duration of diabetes, 12 +/- 10 years). METHODS:
      Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were
      assessed to evaluate endothelial dysfunction and vascular smooth muscle
      dysfunction, respectively, by using a novel ultrasound device, UNEXEF18G (Unex
      Co. Ltd., Japan). RESULTS: The FMD and NMD were 6.4 +/- 3.9% and 13.4 +/- 6.6%,
      respectively. No significant differences in FMD were noted between T2DM with and
      without micro- or macroangiopathy; however, NMD in T2DM patients with micro- and
      macroangiopathy was significantly lower than that in T2DM patients without
      angiopathy. NMD decreased with the progression of chronic kidney disease (CKD)
      stage (p = 0.005), but not FMD (p = 0.071). On multiple regression analysis,
      significant independent contributors to FMD were age, smoking, systolic blood
      pressure, glycosylated hemoglobin, and serum total cholesterol, while those for
      NMD were age, systolic blood pressure, and waist circumference. CONCLUSION: The
      relationship of vascular complications and cardiovascular risk factors with NMD
      is different from that with FMD in type 2 diabetic patients.

PMID- 22146237
TI  - Thiobarbituric acid reactive substances as a biomarker for coronary heart
      disease.

PMID- 22146238
TI  - Atorvastatin does not affect ischaemia-induced phosphatidylserine exposition in
      humans in-vivo.
AB  - AIM: Statins can induce pharmacologic preconditioning and thereby reduce infarct
      size. Cellular phosphatidylserine (PS) exposition occurs in the course of
      ischaemia and reperfusion and has been associated with injury. In this experiment
      we studied the effect of atorvastatin on PS exposition after a standardised
      ischaemia and reperfusion challenge. METHODS: In a double-blind randomised cross
      over trial 30 healthy volunteers were allocated to 3 day treatment with
      atorvastatin (80 mg/day) and placebo (n = 24), or placebo treatment twice (n =
      6). At the end of each treatment period, volunteers underwent 10 minutes of
      forearm ischaemic exercise. At reperfusion radiolabeled annexin A5 was
      administered intravenously and Gamma camera imaging of both hands was performed 1
      and 4 hours after reperfusion. RESULTS: Annexin A5 targeting was not different
      between atorvastatin treatment (26.1 +/- 9.8% and 24.0 +/- 9.5% respectively at 1
      and 4 hours after reperfusion) and placebo treatment (25.6 +/- 11.0% and 24.5 +/-
      10.7%) (p = 0.99). Our time control experiment did not reveal a carry-over
      effect. CONCLUSIONS: Our results show that treatment with atorvastatin 80 mg does
      not reduce forearm PS exposition after ischaemic exercise. This suggests that the
      role of PS exposure in the prevention of ischemia and reperfusion injury by short
      term treatment with atorvastatin is limited.

PMID- 22146239
TI  - Novel TNF-alpha receptor 1 antagonist treatment attenuates arterial inflammation
      and intimal hyperplasia in mice.
AB  - AIM: Tumor necrosis factor receptor 1 (TNFR1) participates importantly in
      arterial inflammation in genetically altered mice; however it remains
      undetermined whether a selective TNFR1 antagonist inhibits arterial inflammation
      and intimal hyperplasia. This study aimed to determine the effect and mechanism
      of a novel TNFR1 antagonist in the suppression of arterial inflammation. METHODS:
      We investigated intimal hyperplasia in IL-1 receptor antagonist-deficient mice
      two weeks after inducing femoral artery injury in an external vascular cuff
      model. All mice received intraperitoneal injections of TNFR1 antagonist (PEG
      R1antTNF) or normal saline twice daily for 14 days. RESULTS: PEG-R1antTNF
      treatment yielded no adverse systemic effects, and we observed no significant
      differences in serum cholesterol or blood pressure in either group; however,
      selective PEG-R1antTNF treatment significantly reduced intimal hyperplasia
      (19,671+/-4,274 vs. 11,440+/-3,292 um(2); p=0.001) and the intima/media ratio
      (1.86+/-0.43 vs. 1.34+/-0.36; p=0.029), compared with saline injection.
      Immunostaining revealed that PEG-R1antTNF inhibits Nuclear factor-kappaB (NF
      kappaB), suppressing smooth muscle cell (SMC) proliferation and decreasing
      chemokine and adhesion molecule expression, and thus decreasing intimal
      hyperplasia and inflammation. CONCLUSIONS: Our data suggest that PEG-R1antTNF
      suppresses SMC proliferation and inflammation by inhibiting NF-kappaB. This study
      highlights the potential therapeutic benefit of selective TNFR1 antagonist
      therapy in preventing intimal hyperplasia and arterial inflammation.

PMID- 22146240
TI  - A PCR-based method to identify Entomophaga spp. infections in North American
      grasshoppers.
AB  - A PCR-based method was developed for the detection and identification of two
      species of grasshopper-specific pathogens belonging to the genus Entomophaga in
      North America, Entomophaga calopteni and Entomophaga macleodii. Two separate sets
      of primers specific for amplification of a DNA product from each species of
      Entomophaga as well as a positive control were utilized. Grasshoppers were
      collected from two sites in Mexico during an epizootic with grasshoppers found in
      "summit disease", typical of Entomophaga infections. There was a preponderance of
      Melanopline grasshoppers infected by E. calopteni. The described method is an
      accurate tool for identification of North American grasshopper infections by
      Entomophaga species.

PMID- 22146241
TI  - Is there a link between shell morphology and parasites of zebra mussels?
AB  - The shell morphology of zebra mussels, Dreissena polymorpha, was analyzed to
      determine if alterations in shell shape and asymmetry between valves were related
      to its infection status, i.e. infected or not by microparasites like ciliates
      Ophryoglena spp. or intracellular bacteria Rickettsiales-like organisms (RLOs),
      and by macroparasites like trematodes Phyllodistomum folium and Bucephalus
      polymorphus. For microparasites, two groups of mussels were observed depending on
      shell measurements. Mussels with the more concave shells were the most
      parasitized by ciliates. This could be more a consequence than a cause and we
      hypothesized that a modification of the water flow through the mantle cavity
      could promote the infection with a ciliate. There were more RLOs present in the
      most symmetrical individuals. A potential explanation involved a canalization of
      the left-right asymmetry as a by-product of the parasite infection. Trematode
      infections were associated with different responses in valve width. Females
      infected by P. folium displayed significantly higher symmetry in valve width
      compared with non-infected congeners, whereas the infection involved an opposite
      pattern in males. B. polymorphus was also linked to a decrease in valve width
      asymmetry. This study suggested that a relationship exists between parasitism and
      shell morphology through the physiological condition of host zebra mussels.

PMID- 22146242
TI  - A new variational calculation for  N-dimensional polarons in the strong-coupling
      limit.
AB  - A novel variational approach is presented for the calculation of the ground-state
      energy of the polaron in arbitrary N dimensions in the strong-coupling limit. By
      using the phonon coherent state to represent the wavefunction of phonons, a self
      consistent integro-differential equation for the electron wavefunction is
      derived. The calculated results of the ground-state energy for N = 1, 2 and 3
      agree well with the best results in the literature. It is also found that, for
      arbitrary N, the present results are less than the Feynman path integral ones by
      small percentages. It is proposed that this approach should be universal for
      systems involving polarons in the strong-coupling regime.

PMID- 22146245
TI  - An interview with Professor Frank Yuh-Yuan Shiau. [Interview by Li-Deh Lin].

PMID- 22146244
TI  - Effect of an hyperbaric nitrogen narcotic ambience on arginine and citrulline
      levels, the precursor and co-product of nitric oxide, in rat striatum.
AB  - Previous studies performed in the laboratory have shown that nitrogen narcosis
      induces a decrease in striatal glutamate and dopamine levels. Although we
      stimulated the N-methyl-D-aspartate (NMDA) receptor, an important glutamate
      receptor required for motor and locomotor activity managed by the striatum, and
      demonstrated that the receptor was effective when exposed to nitrogen at 3MPa, it
      was not possible to return the striatal glutamate level to its base values. We
      conclude that it was the striatopetal neurons of the glutamatergic pathways that
      were mainly affected in this hyperbaric syndrome, without understanding the
      principal reasons. Hence we sought to establish what happens in the vicinity of
      the plasma membrane, downstream the NMDA-Receptor, and we used the hypothesis
      that there could be neuronal nitric oxide synthase (nNOS) disturbances. A
      microdialysis study was performed in rat striatum in order to analyse levels of
      citrulline, the NO co-product, and arginine, the NO precursor. Those both NO
      metabolites were detectable with an HPLC coupled to a fluorimetric detector.
      Exposure to pressurized nitrogen induced a reduction in citrulline (-18.9%) and
      arginine (-10.4%) levels. Under the control normobaric conditions, the striatal
      NMDA infusion enhanced the citrulline level (+85.6%), whereas under 3 MPa of
      nitrogen, the same NMDA infusion did not change the citrulline level which
      remains equivalent to that of the baseline. The level of arginine increased
      (+45.7%) under normobaric conditions but a decrease occurred in pressurized
      nitrogen (-51.6%). Retrodialysis with Saclofen and KCl in the prefrontal cortex
      under normobaric conditions led to an increase in striatal levels of citrulline
      (+30.5%) and a decrease in arginine levels (-67.4%). There was no significant
      difference when nitrogen at 3MPa was added. To conclude, the synthesis of
      citrulline/NO is reduced in nitrogen narcosis while it seems possible to activate
      it artificially by infusion. We have suggested that the low glutamate levels
      recorded in nitrogen narcosis induced these dopamine and NO reductions in the
      striatum.

PMID- 22146243
TI  - Emergent role of gasotransmitters in ischemia-reperfusion injury.
AB  - Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) are lipid
      soluble, endogenously produced gaseous messenger molecules collectively known as
      gasotransmitters. Over the last several decades, gasotransmitters have emerged as
      potent cytoprotective mediators in various models of tissue and cellular injury.
      Specifically, when used at physiological levels, the exogenous and endogenous
      manipulation of these three gases has been shown to modulate ischemia/reperfusion
      injury by inducing a number of cytoprotective mechanisms including: induction of
      vasodilatation, inhibition of apoptosis, modulation of mitochondrial respiration,
      induction of antioxidants, and inhibition of inflammation. However, while the
      actions are similar, there are some differences in the mechanisms by which these
      gasotransmitters induce these effects and the regulatory actions of the enzyme
      systems can vary depending upon the gas being investigated. Furthermore, there
      does appear to be some crosstalk between the gases, which can provide synergistic
      effects and additional regulatory effects. This review article will discuss
      several models and mechanisms of gas-mediated cytoprotection, as well as provide
      a brief discussion on the complex interactions between the gasotransmitter
      systems.

PMID- 22146246
TI  - Interpretive and report bias in publications on implants in patients with
      ectodermal dysplasia.

PMID- 22146247
TI  - Does a clinician's sex influence treatment decisions?
AB  - PURPOSE: As more women are entering health professions, the health care system is
      becoming more feminized. This investigation evaluated gender differences in
      clinicians' treatment preferences and decision making in a complex treatment
      situation. MATERIALS AND METHODS: A questionnaire was developed containing
      clinical cases and statements to assess practitioners' opinions on treatment of
      periodontally involved maxillary molars and implant therapy with sinus grafting.
      Data were analyzed with respect to the clinicians' sex, and an overall logistic
      regression was performed to further investigate possible influences of age,
      office location, and specialty. RESULTS: Three hundred forty questionnaires were
      evaluated (response rate: 35.1%). The mean age of female respondents (37%) was 42
      years, and the mean age of male respondents was 46 years. Significantly fewer
      women reported performing implant placement (35% vs 63%), sinus grafting (16% vs
      43%), and periodontal surgery (57% vs 68%). Female practitioners tended to refer
      more patients to specialists. Participants favored sinus grafting more often for
      their spouses than for themselves. Apart from a preference for regenerative
      periodontal surgery among women, no gender differences were observed for
      treatment decisions or views on general statements related to implant preference,
      tooth maintenance, or conventional reconstructive therapies. CONCLUSIONS: With
      similar expert knowledge, treatment decisions were made irrespective of sex.
      While the majority of male care providers performed complex therapies themselves,
      female clinicians referred more patients to specialists.

PMID- 22146248
TI  - Effect of repeated firings on microtensile bond strength of In-Ceram Alumina with
      two different veneering ceramics.
AB  - Microtensile bond strengths of In-Ceram Alumina cores veneered with two ceramics
      after different numbers of firing cycles were evaluated. After In-Ceram Alumina
      cores were fabricated, they were veneered with either Vitadur Alpha or Vita VM7.
      A control group of each core-veneer combination was fired twice, and a second
      group was fired five times to induce thermal fatigue. Obtained microbars were
      subjected to microtensile bond strength tests. Data were analyzed using two-way
      analysis of variance. Microtensile bond strength values for Vita VM7 specimens
      were higher than those for Vitadur Alpha (P < .001). Although the number of
      firing cycles revealed no change in bond strength, the veneering material proved
      to be an important factor.

PMID- 22146249
TI  - Mastication in subjects with extremely shortened dental arches rehabilitated with
      removable partial dentures.
AB  - Mastication was evaluated in subjects presenting extremely shortened dental
      arches (ESDAs) rehabilitated with mandibular free-end removable partial dentures
      (RPDs). Subjects were divided into four groups (n = 10): those with a complete
      dentition, those with ESDAs, and those with ESDAs who were rehabilitated with an
      RPD, who were evaluated both with and without their prostheses. Mastication was
      measured through masticatory performance, time, and ability. RPD wearers showed
      higher masticatory performance (P < .01) and ability (P < .001) and lower
      masticatory time (P < .001) than when not wearing their prostheses as well as
      ESDA subjects who had not received RPD therapy. Those with a complete dentition
      showed the best results (P < .001). It can be suggested that RPDs improve
      mastication in ESDA subjects but without achieving normal mastication levels.

PMID- 22146250
TI  - Implant reconstruction of a large mandibular defect following removal of a
      nonossifying fibroma.
AB  - The fixed implant-supported restoration of this mandibular surgical defect
      deliberately violated the principles of mandibular flexure, crown-to-implant
      ratio, and off-axis loading. A custom-made implant-mounted jig revealed no
      mandibular flexure in this patient, but crown-to-root ratios of up to 39:12 were
      unavoidable. The restoration has needed no maintenance for 14 years. This
      apparent success calls into question the blind application of prevailing clinical
      principles.

PMID- 22146251
TI  - Psychometric properties of the Croatian version of the Orofacial Esthetic Scale
      and suggestions for modification.
AB  - PURPOSE: The aims of this study were to develop a Croatian version of the
      Orofacial Esthetic Scale (OES) and to test its psychometric properties. MATERIALS
      AND METHODS: The English version of the OES was translated into Croatian (forward
      backward method). The original 11-point scale as well as a 5-point scale (1 =
      unsatisfactory, 5 = excellent) were used. Convergent validity was tested on 126
      subjects, and discriminative validity was tested on the same subjects divided
      into four groups: esthetically normal patients (n = 25), esthetically impaired
      patients (n = 42), esthetically normal controls (n = 37), and esthetically
      impaired controls (n = 22). Test-retest reliability was tested on 43 subjects.
      Responsiveness was tested on 32 esthetically impaired patients who received
      prosthodontic treatment. RESULTS: An additional explanation was added to the
      first two items of the OES. Convergent validity was confirmed by the association
      between OES scores and self-reported oral esthetics and three questions from the
      Oral Health Impact Profile related to esthetics (correlation coefficients ranged
      from 0.734 to 0.811, P < .001). Discriminative validity showed the results as
      predicted. Test-retest reliability showed high intraclass correlation (0.79 to
      0.95) and no significant differences between the two administrations of the 5
      point OES scale (P > .05). The 11-point OES scale showed significant differences
      for questions 3 and 8 (P < .01). Internal consistency showed high Cronbach alpha
      values (0.802 to 0.962). Responsiveness was confirmed by a significant difference
      between baseline and follow-up (P < .001) and a high effect size. CONCLUSION:
      Psychometric properties of the Croatian version of the OES render the instrument
      suitable for the assessment of esthetics in Croatia. The authors recommend
      changing the first two items by adding the explanation that the questions are
      related to the lower third of the face and using the 5-point scale for rating.

PMID- 22146252
TI  - Mandibular overdentures with immediate loading: satisfaction and quality of life.
AB  - PURPOSE: The aim of this study was to verify quality of life related to oral
      health and satisfaction with dentures. Conventional mandibular complete dentures
      were converted to overdentures retained by two implants with immediate loading
      (bar-clip system, n = 16). MATERIALS AND METHODS: The Brazilian short version of
      the Oral Health Impact Profile (OHIP-14Br) was used to evaluate the impact of
      oral health on quality of life. Satisfaction with the prostheses was obtained by
      means of a questionnaire addressing satisfaction with the present prostheses and
      through use of a visual analog scale (VAS). RESULTS: The results of the OHIP-14Br
      questionnaire were verified at 3 and 6 months after conversion from complete
      dentures to a mandibular overdenture. The satisfaction questionnaire for the
      mandibular prostheses obtained 43.75% satisfaction before conversion and 100%
      satisfaction at 1 week and 3 and 6 months after conversion. The satisfaction
      results of the prostheses, both maxillary and mandibular, were 68.75% before
      conversion, 93.75% at 1 week and 3 months after conversion, and 87.5% at 6
      months. There was an immediate improvement in patients' satisfaction with the
      mandibular overdenture prostheses regarding stability and retention (Friedman
      test, P = .000) and quality of life (Friedman test, P = .001). CONCLUSION: The
      improvement seen justifies the immediate loading approach used in this study.

PMID- 22146253
TI  - Influence of two functional complete-denture impression techniques on patient
      satisfaction: dentist-manipulated versus patient-manipulated.
AB  - This preliminary clinical study aimed to identify the impact of two border
      molding techniques (dentist-manipulated and patient-manipulated) on patient
      satisfaction, the occlusal force at denture dislodgment, and number of pressure
      sores. Salivary flow rate and residual ridge resorption were analyzed as
      covariates. Thirty-six edentulous patients in need of a relining of their
      existing maxillary denture were included. After relining, no significant
      influence of the border-molding technique on any of the variables investigated
      could be identified. It can be concluded that the impact of the border-molding
      technique on patient satisfaction and denture function probably has been
      overestimated in the past.

PMID- 22146254
TI  - Implant dentistry curriculum in undergraduate education: part 2-program at the
      Albert-Ludwigs University, Freiburg, Germany.
AB  - PURPOSE: The aim of this study was to describe the didactic and clinical
      undergraduate implant dentistry program of the Albert-Ludwigs University,
      Freiburg, Germany, with emphasis on the clinical implant experience. MATERIALS
      AND METHODS: A detailed description of the implant curriculum at Albert-Ludwigs
      University is given with documented exemplary cases and additional flow charts.
      RESULTS: All students participate in 28 hours of lectures and approximately 64
      hours of seminars with hands-on courses and gain clinical experience. All
      undergraduate students are eligible to place and restore oral implants. Emphasis
      is placed on prosthetic-driven planning of implant positions, three-dimensional
      imaging, and computer-guided implant placement. Implant restorations performed by
      undergraduate students comprise single crowns and small multiunit fixed dental
      prostheses in partially edentulous posterior maxillae and anterior or posterior
      mandibles, implant-retained overdentures (snap attachment) in edentulous
      patients, and telescopic fixed-removable dental prostheses on remaining teeth and
      strategically placed additional implants. Over the past 2.5 years, 51 patients
      were treated with 97 dental implants placed by students in the undergraduate
      program. Seventy-one restorations were inserted: 60.6% single crowns, 7% fixed
      dental protheses, 21.1% overdentures, and 11.3% telescopic fixed-removable dental
      prostheses. The implant survival rate was 98.9%. CONCLUSIONS: Because survival
      rates for dental implants placed and restored by students are comparable to those
      of experienced dentists, oral implant dentistry should be implemented as part of
      the undergraduate dental curriculum.

PMID- 22146255
TI  - Effect of implant diameter on reliability and failure modes of molar crowns.
AB  - The reliability and failure modes of molar crowns supported by three different
      implant-supported designs were tested according to the following groups: group 1,
      one standard-diameter implant (3.75 mm); group 2, one narrow-diameter implant (3
      mm); and group 3, two narrow-diameter implants (3 mm). Loads were applied as
      mouth-motion cycles using a step-stress accelerated life-testing method. ? values
      for groups 1 and 3 (1.57 and 2.48, respectively) indicated that fatigue
      accelerated the failure of both groups, but not for group 2 (0.39). Abutment
      screw failure was the chief failure mode. Strength and reliability were
      significantly higher for groups 1 and 3 compared to group 2.

PMID- 22146256
TI  - Application times for the single-step/double-mix technique for impression
      materials in clinical practice.
AB  - Hydrophilicity of unset impression materials underlies changes occurring during
      working time. Hence, the clinical application time when impression materials
      contact oral tissues after mixing may play a critical role in successful
      impressions. The aim of this study was to analyze the clinical time course of
      impression taking applying the single-step/double-mix technique. Application
      times of 86 impressions, comprising 265 prepared teeth and 46 implants, taken by
      14 different clinicians at a university dental clinic were analyzed. The mean
      time from loading the impression tray until its final position in the patient's
      mouth (total application time) was 51.2 seconds; confidence intervals were 46.9
      (lower limit) and 55.5 (upper limit). The number of registered teeth and implants
      did not influence the duration of impression taking. Related to wettability data,
      several polyvinyl siloxane impression materials show decreased hydrophilicity
      with respect to estimated application times. The authors suggest considering
      clinically relevant application times for impression taking in future in vitro
      studies on physicochemical characteristics of impression materials.

PMID- 22146257
TI  - A systematic review of ceramic inlays in posterior teeth: an update.
AB  - PURPOSE: Ceramic materials, first introduced in restorative dentistry in the late
      18th century, offer a wide range of possibilities and exhibit esthetic
      properties. The last systematic reviews on the subject of ceramic inlays were
      published in 2003. All articles published up to 2001 were surveyed regarding the
      longevity, esthetic qualities, and postoperative discomfort associated with the
      use of ceramic inlays compared to other restorative materials. The present review
      aimed to establish the current state of the art. MATERIALS AND METHODS: Using
      methods identical to those of previous reviews, the literature from 2001 up to
      and including 2009 was assessed. The scientific and methodologic qualities of all
      articles describing the use of ceramic inlays were established. Articles
      comparing the results of ceramic inlays to other types of inlays were then used
      to answer the hypotheses that there were no differences in longevity,
      postoperative sensitivity, or color match. RESULTS: Three articles comparing the
      results of ceramic to other materials were analyzed further. No new reliable
      evidence was found to update the answer to the hypothesis that there was no
      difference in longevity, at least in the first year postoperative. The evidence
      found regarding postoperative discomfort backs the previous conclusion that there
      was no difference. New evidence found on color matching suggests that there is no
      significant difference in color match over assessment periods of up to 57 months.
      CONCLUSION: Current ceramic materials in inlay restorations seem to perform as
      well as other restorative options for selected properties during the first years
      after placement.

PMID- 22146258
TI  - Testing a multistage rating scale for clinical evaluation of all-ceramic
      surfaces.
AB  - PURPOSE: This study tested the applicability of a multistage rating scale based
      on modified California Dental Association (CDA) criteria and the original
      criteria of the CDA for surface evaluation of all-ceramic restorations with the
      use of dental stone replicas, photographs, and scanning electron microscopy
      (SEM). MATERIALS AND METHODS: Two examiners clinically evaluated 105 all-ceramic
      restoration units in the posterior region after a mean observation period of 42.2
      months; the examiners employed the CDA criteria and a detailed six-stage rating
      scale. In addition, standardized photographs and gypsum stone and epoxy replicas
      based on impressions were analyzed blindly using the same rating scales and
      examiners. SEM images of gold-coated epoxy replicas enabled indirect ceramic
      surface evaluation, serving as the gold standard to control indirect evaluation
      and clinical findings. The Cohen kappa was applied to test for concordance;
      intraclass correlations and Spearman rank correlations were calculated. RESULTS:
      Statistically significant rating correlations of the clinical situation,
      photographs, and stone replicas with the SEM photographs were generated from both
      evaluation systems. With the use of the multistage rating scale, the highest
      rating correlation was found for stone replica-SEM (r = 0.61, P < .001), and the
      lowest for clinical photography-SEM (r = 0.5, P < .001). CONCLUSIONS: A
      multistage rating scale based on modified CDA criteria is reliable for precise
      assessment of in vivo ceramic surface alterations. Stone replicas were found to
      be better-suited than photographs for the assessment of all-ceramic surface
      alterations and confirmation of clinical ratings.

PMID- 22146259
TI  - Adhesion of maxillofacial silicone elastomer to a fiber-reinforced composite
      resin framework.
AB  - PURPOSE: Recently, fiber-reinforced composite resin (FRC) has been introduced as
      a framework material for maxillofacial silicone prostheses. The purpose of this
      research was to study the tensile bond strength between a room temperature
      polymerized maxillofacial silicone elastomer and a unidirectional FRC. MATERIALS
      AND METHODS: Three different bonding agents were compared. Specimens were loaded
      in tension mode according to ISO 22401 in a universal testing device with a
      crosshead speed of 10 mm/min until bonding failure occurred. The influence of the
      surface characteristics (ground vs intact) was also studied. RESULTS: The highest
      tensile bond strength was seen with Gold Platinum Primer A-330-G, followed by
      Sofreliner primer. One-way analysis of variance revealed that the surface
      treatment of the FRC and the adhesive used had a significant effect on tensile
      bond strength between silicone and FRC (P < .05). Grinding enhanced adhesion,
      especially with Gold Platinum Primer A-330-G and Sofreliner primer. The fracture
      type also changed to more cohesive in nature. CONCLUSION: The FRC substructure
      can successfully be bonded to maxillofacial silicone elastomer by using primer
      containing methyl ethyl ketone and dichloromethane solvent. Bonding can be
      improved by roughening the FRC substrate via grinding.

PMID- 22146260
TI  - Improving mechanical properties of maxillary complete dentures through a
      bioinspired engineering design.
AB  - PURPOSE: This study investigated how ribbed design features, including palatal
      rugae, may be used to significantly improve the structural performance of a
      maxillary denture under load. MATERIALS AND METHODS: A computer-aided design
      model of a generic maxillary denture, incorporating various rib features, was
      created and imported into a finite element analysis program. The denture and
      ribbed features were assigned the material properties of standard denture acrylic
      resin, and load was applied in two different ways: the first simulating a three
      point flexural bend of the posterior section and the second simulating loading of
      the entire palatal region. To investigate the combined use of ribbing and
      reinforcement, the same simulations were repeated with the ribbed features having
      a Young modulus two orders of magnitude greater than denture acrylic resin. For a
      prescribed load, total displacements of tracking nodes were compared to those of
      a control denture (without ribbing) to assess relative denture rigidity. RESULTS:
      When subjected to flexural loading, an increase in rib depth was seen to result
      in a reduction of both the transverse displacement of the last molar and vertical
      displacement at the centerline. However, ribbed features assigned the material
      properties of denture acrylic resin require a depth that may impose on speech and
      bolus propulsion before significant improvements are observed. CONCLUSION: The
      use of ribbed features, when made from a significantly stiffer material (eg,
      fiber-reinforced polymer) and designed to mimic palatal rugae, offer an
      acceptable method of providing significant improvements in rigidity to a
      maxillary denture under flexural load.

PMID- 22146261
TI  - [Metronomic chemotherapy in 2011: update and perspectives].
AB  - Angiogenesis is crucial for the growth and metastasis of many cancers. A series
      of new inhibitors of angiogenesis are now in intensive development. Recent
      preclinical studies suggest that frequent administration of certain conventional
      cytotoxic agents at low doses increases their putative antiangiogenic activity.
      Moreover, many clinical trials confirm efficacy of this metronomic chemotherapy
      in terms of clinical benefice and survival prolongation. Combining metronomic
      chemotherapy with hormonotherapy, angiogenesis inhibitors and radiotherapy
      increases efficacy. Many biomarkers are used to predict optimal drugs and
      appropriate use of them. This review describes experimental and clinical studies
      published and discuss its potential uses and limits.

PMID- 22146262
TI  - Rare solvent annealing effective benzo(1,2-b:4,5-b')dithiophene-based low band
      gap polymer for bulk heterojunction organic photovoltaics.
AB  - A newly synthesized benzo(1,2-b:4,5-b')dithiophene-based low band-gap copolymer
      pBCN is amenable to solvent annealing in the fabrication of organic
      photovoltaics, of which power conversion efficiency is greatly improved to 4.2%
      with PC(61)BM or 4.9% with PC(71)BM.

PMID- 22146264
TI  - Expanding clinical nurse specialist practice internationally.

PMID- 22146265
TI  - Reader responds to APRN Consensus Model.

PMID- 22146267
TI  - Health information exchange: implications for the clinical nurse specialist.

PMID- 22146268
TI  - Therapeutic hypothermia after cardiac arrest: improving adherence to national
      guidelines.

PMID- 22146269
TI  - Prescription opioid abuse update for the clinical nurse specialist.

PMID- 22146270
TI  - Adherence to sedation withdrawal protocols and guidelines in ventilated patients.
AB  - PURPOSE/OBJECTIVES: The purpose of this article is to delineate what we know
      about adherence with sedation withdrawal protocols and guidelines. Reasons for
      lack of adherence and associated outcomes are explored in addition to potential
      solutions. BACKGROUND/RATIONALE: Research has demonstrated the positive outcomes
      associated with sedation withdrawal in ventilated patients, such as decreased
      ventilator duration, intensive care unit and hospital length of stay, and
      mortality. Subsequently, protocols and guidelines used in the trials have been
      introduced into clinical practice to ensure that practice is evidence based and
      that clinical outcomes improve. Unfortunately, evidence suggests that adherence
      to these protocols and guidelines is poor. DESCRIPTION OF PROJECT/INNOVATION: A
      literature review was performed for years 1998-2011 using PubMed, Ovid MEDLINE,
      and Cumulative Index to Nursing and Allied Health Literature. Searches included
      the key terms sedation management, sedation interruption, sedation withdrawal,
      mechanical ventilation, protocol adherence, guideline adherence, sedation
      management adherence, sedation interruption adherence, and mechanical ventilation
      weaning. OUTCOMES: Twelve articles that focused on adherence to sedation
      withdrawal protocols or guidelines were reviewed to determine adherence rates and
      reasons for lack of adherence. An additional 5 research articles testing the
      efficacy of sedation withdrawal protocols or guidelines in practice were reviewed
      to determine clinical outcomes associated with their use.
      INTERPRETATION/CONCLUSIONS: Despite the current emphasis on the importance of
      sedation withdrawal in mechanically ventilated patients, protocols and guidelines
      that are designed to ensure adherence do not appear to be working. Multiple
      reasons for the lack of adherence are suggested in the literature, including
      caregiver perceptions, complexity, and processes of care. In addition, clinician
      education, unit culture, and philosophy may all play a part. IMPLICATIONS: The
      findings described in this article suggest that adherence to sedation withdrawal
      protocols and guidelines is not good despite perceptions to the contrary. The
      article delineates potential solutions as suggested by the authors of the
      reviewed articles and those of the author of this article.

PMID- 22146271
TI  - Bowel sounds and monitoring gastrointestinal motility in critically ill patients.
AB  - PURPOSE: The aims of this study were to determine whether bowel sounds
      auscultation is necessary in critically ill patients and to forecast the prospect
      of bowel sounds as a monitoring measurement in the intensive care unit (ICU).
      BACKGROUND: It has been suggested recently that bowel sounds are not an objective
      indicator of bowel motility and that auscultation should be abandoned. This has
      led to confusion as to whether bowel sounds auscultation should be continued in
      the ICU. DESCRIPTION OF THE PROJECT: A literature review of articles about bowel
      sounds and monitoring gastrointestinal motility in critically ill patients was
      conducted. OUTCOME: At present, there are no more suitable indicators for bedside
      monitoring of bowel function and motility than bowel sounds. Although they lack
      objectivity, bowel sounds give a lot of useful information about gastrointestinal
      motility. The problems are how to improve practice and assessment standards and
      enhance the precision of auscultation devices. CONCLUSION: Bowel sounds
      auscultation is necessary in the ICU. Effective application in critically ill
      patients requires reasonable practice and precise instrumentation.

PMID- 22146272
TI  - Risk determination after an acute myocardial infarction: review of 3 clinical
      risk prediction tools.
AB  - PURPOSE: The objective of the study was to provide comprehensive information for
      the clinical nurse specialist (CNS) on commonly used clinical prediction (risk
      assessment) tools used to estimate risk of a secondary cardiac or noncardiac
      event and mortality in patients undergoing primary percutaneous coronary
      intervention (PCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND:
      The evolution and widespread adoption of primary PCI represent major advances in
      the treatment of acute myocardial infarction, specifically STEMI. The American
      College of Cardiology and the American Heart Association have recommended early
      risk stratification for patients presenting with acute coronary syndromes using
      several clinical risk scores to identify patients' mortality and secondary event
      risk after PCI. Clinical nurse specialists are integral to any performance
      improvement strategy. Their knowledge and understandings of clinical prediction
      tools will be essential in carrying out important assessment, identifying and
      managing risk in patients who have sustained a STEMI, and enhancing discharge
      education including counseling on medications and lifestyle changes. DESCRIPTION:
      Over the past 2 decades, risk scores have been developed from clinical trials to
      facilitate risk assessment. There are several risk scores that can be used to
      determine in-hospital and short-term survival. This article critiques the most
      common tools: the Thrombolytic in Myocardial Infarction risk score, the Global
      Registry of Acute Coronary Events risk score, and the Controlled Abciximab and
      Device Investigation to Lower Late Angioplasty Complications risk score. OUTCOME:
      The importance of incorporating risk screening assessment tools (that are
      important for clinical prediction models) to guide therapeutic management of
      patients cannot be underestimated. The ability to forecast secondary risk after a
      STEMI will assist in determining which patients would require the most aggressive
      level of treatment and monitoring postintervention including outpatient
      monitoring. With an increased awareness of specialist assessment tools, the CNS
      can play an important role in risk prevention and ongoing cardiovascular health
      promotion in patients diagnosed with STEMI. CONCLUSION/IMPLICATIONS FOR PRACTICE:
      Knowledge of clinical prediction tools to estimate risk for mortality and risk of
      secondary events after PCI for acute coronary syndromes including STEMI is
      essential for the CNS in assisting with improving short- and long-term outcomes
      and for performance improvement strategies. The risk score assessment utilizing a
      collaborative approach with the multidisciplinary healthcare team provides for
      the development of a treatment plan including any invasive intervention strategy
      for the patient.

PMID- 22146273
TI  - Collaborative Healthcare Immersive Learning Dynamic: transitioning to simulation
      based learning.
AB  - PURPOSE: This article describes an innovation representing a paradigm shift away
      from the traditional nursing skills fair passive method of learning toward a
      dynamic, immersive learning experience utilizing simulation. BACKGROUND: There
      are many hospitals that review yearly competencies through a skills fair
      methodology. There is no evidence to support that this method of education and
      training has any direct correlation to better nursing care at the bedside,
      enhanced patient outcomes, or retained knowledge or skills. DESCRIPTION OF THE
      INNOVATION/OUTCOME: We describe the process of successfully transitioning from
      traditional skills fairs to simulation-based skills fairs called CHILD
      (Collaborative Healthcare Immersive Learning Dynamic). IMPLICATIONS: With this
      pioneering approach, institutions can reallocate funds and utilize simulation to
      more effectively provide education, training, and competency validation.

PMID- 22146274
TI  - Seeing the glass half full: benefits to the lived experiences of female primary
      caregivers of children with autism.
AB  - PURPOSE: Autism spectrum disorders are the most common developmental disorders,
      affecting 1 in 165 Canadian children. Although the experiences of the caregivers
      of children with autism have been examined to some extent, a thorough
      investigation of the benefits of this experience is warranted. METHODS: The lived
      experiences of 8 married female primary caregivers of children with autism were
      assessed through a phenomenological study involving background questionnaires and
      one-on-one, semistructured interviews. All recruited participants completed the
      study. RESULTS: Benefits were found in all areas of questioning, including
      financial, social, familial, health, and employment implications, in addition to
      benefits arising from activities and involvements taken on as a result of raising
      a child with autism. The findings shed light on an unconventional aspect of the
      effects of raising a child with autism. CONCLUSIONS: Costs to these women's
      experiences were not predominant, and benefits arising from the caregiving role
      lead to positive accounts of their lived experiences. Results have broader
      implications for the understanding of the primary caregiver situation and the
      improvement of interactions with individuals with these lived experiences. In
      this way, clinical nurse specialists may encourage and contribute to support
      systems that foster a positive experience for caregivers of children with autism
      spectrum disorder, the children they care for, and their families.

PMID- 22146275
TI  - Sharron D. Coffie.

PMID- 22146276
TI  - The visitor.

PMID- 22146277
TI  - Host bone response to polyetheretherketone versus porous tantalum implants for
      cervical spinal fusion in a goat model.
AB  - STUDY DESIGN: In vivo assessment of polyetheretherketone (PEEK) and porous
      tantalum (TM) cervical interbody fusion devices in a goat model. OBJECTIVE:
      Directly compare host bone response to PEEK and TM devices used for cervical
      interbody fusion. SUMMARY OF BACKGROUND DATA: PEEK devices are widely used for
      anterior cervical discectomy and fusion but are nonporous and have limited
      surface area for bone attachment. METHODS: Twenty-five goats underwent single
      level anterior cervical discectomy and fusion and were alternately implanted with
      TM (n = 13) or PEEK devices (n = 12) for 6, 12, and 26 weeks. Both devices
      contained a center graft hole (GH), filled with autograft bone from the animal's
      own iliac crest. The percentage of bone tissue around the implant, percentage of
      the implant surface in direct apposition with the host bone, and evidence of bone
      bridging through the implant GH were assessed by using backscattered electron
      imaging. Bone matrix mineral apposition rate was determined through fluorochrome
      double labeling, and sections were stained for histological analysis. RESULTS:
      The TM-implanted animals had significantly greater volumes of bone tissue at the
      implant interface than the PEEK animals at all-time points. The TM animals also
      had a significantly greater average mineral apposition rate in the GH region at 6
      and 12 weeks than the PEEK animals. No difference was observed at 26 weeks. A
      greater number of TM-implanted animals demonstrated connection between the
      autograft bone and both vertebrae compared with the PEEK implants. Histological
      staining also showed that the TM devices elicited improved host bone attachment
      over the PEEK implants. CONCLUSION: The TM implants supported bone growth into
      and around the implant margins better than the PEEK devices. TM's open cell
      porous structure facilitated host bone ingrowth and bone bridging through the
      device, which could be beneficial for long-term mechanical attachment and support
      in clinical applications.

PMID- 22146278
TI  - Correlation of posterior ligamentous complex injury and neurological injury to
      loss of vertebral body height, kyphosis, and canal compromise.
AB  - STUDY DESIGN: Retrospective, case-control study. OBJECTIVE: The purpose of this
      study was to determine if thoracolumbar vertebral body collapse, translation, or
      canal compromise (CC) is associated with injury to the posterior ligamentous
      complex (PLC) or neurological elements. SUMMARY OF BACKGROUND DATA:
      Radiographical parameters, including loss of vertebral body height (LOVBH),
      vertebral body translation, local kyphosis (LK), and CC, are often used as
      indicators of spinal instability. The hypothesis of this study was that LOVBH
      greater than 50%, LK greater than 20 degrees , translation greater than 3.5 mm,
      or CC greater than 50% is associated with ligamentous and neurological injury.
      METHODS: Retrospective review of prospectively collected spinal cord injury
      database was performed. Inclusion criteria include consecutive patients with
      thoracolumbar burst fractures. Exclusion criteria include flexion-distraction
      injuries and pathological fractures. Computed tomographic scan measurements of
      the spine were performed by 2 experienced spine surgeons blinded to magnetic
      resonance imaging results. On magnetic resonance imaging, the supraspinous
      ligament, interspinous ligament, ligamentum flavum, facet joints, and disc were
      graded as intact, indeterminate, or disrupted. American Spinal Injury Association
      (ASIA) score and Frankel Scale score were recorded. Spearman correlation
      coefficients were calculated to evaluate relationships between vertebral body
      measurements, ligamentous injury, and neurological injury. RESULTS: Forty-six
      patients were included in the study. Ten patients had kyphosis greater than 20
      degrees , 1 patient had kyphosis greater than 30 degrees , and 9 patients had
      LOVBH greater than 50%. There were 34 patients with vertebral body translation
      greater than 3.5 mm and 15 patients with CC greater than 50%. Sixteen patients
      had ligamentous injury. There was a significant correlation between subjacent
      segment translation greater than 3.5 mm and ligamentous injury (R = 0.323, P =
      0.029) and ASIA motor score (R = -0.379, P = 0.009). There was no significant
      correlation between ligamentous injury or neurological injury and the following
      threshold parameters: LOVBH greater than 50%, vertebral body kyphosis greater
      than 20 degrees , caudal or cephalad interspinous widening greater than 7 mm, CC
      greater than 50%, and sagittal transverse ratio less than 0.48. CONCLUSION: The
      results of this study indicate that LOVBH greater than 50% and LK greater than 20
      degrees  are not predictive of PLC injury in thoracolumbar burst fractures.
      Translation greater than 3.5 mm was associated with PLC injury. The PLC and
      neural elements should be directly assessed with magnetic resonance imaging if
      there is clinical concern.

PMID- 22146279
TI  - Innovation in growing rod technique: a study of safety and efficacy of a
      magnetically controlled growing rod in a porcine model.
AB  - STUDY DESIGN.: Prospective in vivo randomized study. OBJECTIVE.: To evaluate the
      safety and efficacy of a distraction-based magnetically controlled growing rod
      (MCGR) in a porcine model. SUMMARY OF BACKGROUND DATA.: A high number of
      complications related to frequent surgical rod lengthenings has been a generally
      accepted outcome in growing rod surgery for early-onset scoliosis. A potentially
      safer technique is a system that does not require repetitive surgery. METHODS.:
      Seven-month-old pigs were randomly assigned to an experiment group (EG; n = 6)
      and a sham group (SG; n = 3). One animal in the EG became paralyzed because of a
      misplaced pedicle screw and was killed per the study protocol. Therefore, a total
      of 8 animals completed the study. The EG underwent weekly spine distraction using
      the MCGR. Spinal height was assessed by vertebral unit height measurements on
      weekly lateral radiographs. RESULTS.: A total of 49 mm of distraction across the
      unfused vertebral levels was planned during a 7-week period (7 mm per wk).
      Radiographical analysis of the MCGR device revealed an average distraction of 39
      mm (range, 32-46 mm), resulting in achievement of 80% of predicted spinal height.
      Prior to removal of implants, spinal height for the EG was similar to the SG.
      However, accelerated increase in vertebral unit height was noted in the EG during
      the 3-week period after implant removal, which resulted in significantly greater
      overall spinal height in the EG (32.2% vs. 11.7%, P <= 0.05). No MCGR-related
      complications occurred. CONCLUSION.: The MCGR provided 80% of predicted spinal
      height by noninvasive remote distraction in this animal model. The accelerated
      increase in spinal height of the experimental animals after implant removal was
      an unexpected finding which requires additional research to better understand the
      effect of distraction on spinal growth. This study establishes a foundation for
      future research in an attempt to use a less invasive technique in distraction
      based correction of early-onset scoliosis.

PMID- 22146280
TI  - Effect of core stability exercises on feed-forward activation of deep abdominal
      muscles in chronic low back pain: a randomized controlled trial.
AB  - STUDY DESIGN: A randomized controlled trial. OBJECTIVE: To investigate feed
      forward activation or timing of abdominal muscle activation in response to rapid
      shoulder flexion after 8 weeks with core stability exercises, sling exercises, or
      general exercises in chronic nonspecific low back pain (LBP) patients. SUMMARY OF
      BACKGROUND DATA: Delayed onset in abdominal muscles has been associated with LBP.
      Low load exercises to volitionally activate the transversus abdominis were
      introduced to restore trunk muscle activation deficits. More forceful co
      contraction exercises have been advocated by others. This study explored whether
      abdominal muscle onset changed after low-load core stability exercises, high-load
      sling exercises, or general exercises. METHODS: Subjects (N = 109) with chronic
      nonspecific LBP of at least 3 months' duration were randomly assigned to 8 weekly
      treatments with low-load core stability exercises, high-load stabilizing
      exercises in slings, or general exercises in groups. Primary outcome was onset
      recorded bilaterally by m-mode ultrasound imaging in the deep abdominal muscles
      in response to rapid shoulder flexion. RESULTS: No or small changes were found in
      onset after treatment. Baseline adjusted between group differences showed a 15 ms
      (95% confidence interval [CI], 1-28; P = 0.03) and a 19 ms (95% CI, 5-33; P <
      0.01) improvement with sling relative to core stability and general exercises,
      respectively, but on 1 side only. There was no association between changes in
      pain and onset over the intervention period (R <= 0.02). CONCLUSION: Abdominal
      muscle onset was largely unaffected by 8 weeks of exercises in chronic LBP
      patients. There was no association between change in onset and LBP. Large
      individual variations in activation pattern of the deep abdominal muscles may
      justify exploration of differential effects in subgroups of LBP.

PMID- 22146281
TI  - Cervical myelopathy after cervical total disc arthroplasty: case report and
      literature review.
AB  - STUDY DESIGN: Case report and literature review. OBJECTIVE: This article reports
      2 cases in which the patients accepted revision surgery after cervical total disc
      arthroplasty (CTDA) because of iatrogenic neurological injury. SUMMARY OF
      BACKGROUND DATA: CTDA has been increasingly investigated to treat cervical
      degenerative disc disease. However, there are limited reports focused on its
      complications, especially the neurological complications after the procedure.
      METHODS: A 52-year-old man underwent total disc arthroplasty for C5-C6, but
      immediately after surgery, he experienced paralysis of his upper and lower limbs.
      Radiographical images indicated residual compression to the spinal cord in the
      level of C5-C6. Another patient, a 60-year-old man, underwent total disc
      arthroplasty for C4-C5. Afterward, he experienced severe neck pain and paralysis
      of upper and lower limbs. He was unresponsive to conservative treatments; thus, a
      laminectomy was performed 3 months later. However, little improvement was
      observed. Radiographical images indicated kyphosis and spinal cord compression at
      the level of C4-C5. Furthermore, both cases showed a high signal in the spinal
      cord by T2-weighted magnetic resonance image, suggestive of spinal cord injuries.
      RESULTS: Revision surgeries were performed in both cases. Cervical implants were
      first removed by the anterior approach, and fusion was then performed after a
      complete decompression. Motor examination of the patient in case 1 showed grade 3
      strength in both of his hands and feet 6 months after revision surgery. In case
      2, the patient's severe neck pain was resolved at the early postoperative stage.
      Motor examination showed grade 1 strength in both of his hands and feet 3 months
      after revision surgery. CONCLUSION: On the basis of presented cases and other
      reports, the surgical goals in these patients were prioritized as follows: (1)
      safe and adequate neurological decompression and (2) establishment and
      maintenance of cervical sagittal balance. Moreover, a criterion for selecting
      patients undergoing CTDA needs to be established in order to reduce the
      occurrence of neurological complications associated with the procedure.

PMID- 22146282
TI  - Long-term surgical outcomes of spinal meningiomas.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate the treatment
      strategies for spinal meningioma. SUMMARY OF BACKGROUND DATA: Although previous
      studies have demonstrated favorable surgical outcomes for spinal meningioma, with
      a low incidence of tumor recurrence, few have examined long-term surgical
      outcomes. METHODS: The influence of patient age, surgical margin status (Simpson
      grade), tumor location, and histological subtype on tumor recurrence were
      examined retrospectively. In addition, the resected dura mater from Simpson grade
      I cases was examined for invasive tumor cells and compared with the presence or
      absence of a dural tail sign on magnetic resonance image. RESULTS: Complete
      resection (Simpson grades I and II) was performed in 62 patients. Among them, the
      tumor recurrence rate was 9.7%, all in patients who underwent grade II resection
      for ventral spinal lesions. The mean duration to reoperation in these patients
      was 12.2 +/- 5.2 years. Of the 6 patients who underwent incomplete resection
      (Simpson grade III/IV), all required reoperation for tumor recurrence or
      regrowth, 5 years later on average. Patients younger than 50 years at the initial
      surgery had a significantly higher recurrence rate than those aged 50 years or
      older. Histologic examination of 43 dura mater specimens from Simpson grade I
      resection patients revealed tumor cell invasion between the inner and outer
      layers in 15 patients. This invasion was noted in 8 (29%) of 28 patients who were
      negative for the dural tail sign on magnetic resonance image, and in 7 (47%) of
      15 patients who showed a positive dural tail sign. The MIB-1 index reached about
      10% for dumbbell-type meningiomas invading the vertebral body; these were
      associated with repeated recurrence and unfavorable prognosis. CONCLUSION: Long
      term follow-up after surgery for meningiomas indicated that Simpson grade I
      resection should be selected whenever practicable when treating younger patients
      or dumbbell-type meningiomas. Tumors recurred at 12 years, on average, in
      approximately 30% of patients who underwent grade II resection.

PMID- 22146283
TI  - Neurological complications of cervical spine surgery: C5 palsy and intraoperative
      monitoring.
AB  - STUDY DESIGN: Review article. OBJECTIVE: To review the epidemiology, etiology,
      risk factors, prevention, and treatment of neurological complications associated
      with cervical spine surgery. The article focuses on C5 palsy and intraoperative
      neurophysiological monitoring. SUMMARY OF BACKGROUND DATA: Neurological problems
      are the complications most feared by patients and surgeons alike, but,
      fortunately, spinal cord injury is uncommon. C5 palsy is a less severe but much
      more common and perplexing problem. Intraoperative monitoring is widely used in
      cervical spine surgery, but it is unclear how effective it is at preventing
      spinal cord or nerve root injury. METHODS: Narrative and review of the
      literature. RESULTS: The incidence of new, severe motor weakness in 2 or more
      extremities occurring within 12 hours of surgery is 0.18%. The rate in the
      cervical spine is 3 of 1000. The incidence of isolated C5 palsy is much greater;
      the rate varies between 0% and 30%, depending on how the condition is defined and
      which patient group is being analyzed. Numerous theories have been postulated to
      explain the pathogenesis of C5 palsy, and preventative strategies are discussed.
      Approximately 70% of patients recover completely without treatment. The mean time
      to full recovery is 4 to 5 months. Recovery is spontaneous; no treatment has been
      shown to shorten the time to recovery or improve the recovery rate. A systematic
      review of the literature found a high level of evidence that multimodal
      intraoperative monitoring is effective at detecting intraoperative neurological
      injury. The evidence that intraoperative monitoring reduces the rate of new or
      worsened perioperative neurological deficits is not as strong. Algorithms help
      surgeons respond to monitoring alerts and manage neurological deficits that are
      identified postoperatively. CONCLUSION: The keys to managing neurological
      complications in cervical spine surgery are prevention through careful planning,
      appropriate multimodal monitoring, meticulous surgical technique, and decisive
      action when a problem is identified.

PMID- 22146284
TI  - Ossification of the posterior longitudinal ligament of the cervical spine:
      etiology and natural history.
AB  - STUDY DESIGN: Review article. OBJECTIVE: To review the etiology, natural history,
      measurement tools, and image diagnosis of ossification of the posterior
      longitudinal ligament (OPLL) of the cervical spine. SUMMARY OF BACKGROUND DATA:
      OPLL is a well-known disease that causes myelopathy. Genetic factors are very
      important for development of OPLL. However, the pathogenetic gene and natural
      history of OPLL have not been clarified. METHODS: The authors reviewed studies
      about the etiology, natural history, measurement tools, and diagnosis of OPLL,
      which had been performed by the members of the Investigation Committee on the
      Ossification of the Spinal Ligaments of the Japanese Ministry of Health, Labour,
      and Welfare. RESULTS: The prevalence of OPLL in the general Japanese population
      was reported to be 1.9% to 4.3% among people older than 30 years. Genetic factors
      are important for development of OPLL, and some candidate genes have been
      reported. Clinical course of OPLL has been clarified by a prospective long-term
      follow-up study. Some radiographic predictors for development of myelopathy were
      introduced. Image diagnosis of OPLL is easy by plain radiographs, but magnetic
      resonance imaging and computed tomography are useful to determine cord
      compression by OPLL. CONCLUSION: OPLL should be managed on the basis of the
      consideration of its natural history. Elucidation of pathogenetic genes of OPLL
      will introduce a new approach for management of OPLL.

PMID- 22146285
TI  - 2012 Young Investigator Award winner: The distribution of body mass as a
      significant risk factor for lumbar spinal fusion postoperative infections.
AB  - STUDY DESIGN: A retrospective review. OBJECTIVE: The purpose of this study was to
      determine the role in body habitus and weight distribution on developing a
      surgical site infection (SSI). SUMMARY OF BACKGROUND DATA: SSI after lumbar spine
      surgery remains a significant cause of morbidity. The literature demonstrates an
      increased risk of postoperative infections associated with obesity, diabetes, and
      multilevel surgeries. METHODS: A retrospective review was performed on a
      consecutive cohort of 298 adult patients who underwent lumbar spine fusion
      surgeries between 2006 and 2008 at the Duke University Medical Center. Previously
      identified risk factors (i.e., number of levels, diabetes, body mass index [BMI])
      were collected, as well as the horizontal distance from the lamina to the skin
      surface (measured at L4) and thickness of subcutaneous fat at the surgical site.
      RESULTS: Among the 298 patients, 24 (8%) had postoperative infections. Of the
      previously identified risk factors, number of levels (P = 0.0078) was found to be
      significantly associated with infections, whereas BMI (P = 0.16) and diabetes (P
      = 0.13) were found not to be statistically significant. Obesity (BMI >=30) (P =
      0.025), skin to lamina distance (P = 0.046), and thickness of the subcutaneous
      fat (P = 0.035) were found to be significant risk factors for SSI. CONCLUSION:
      Our findings suggest that in obese patients, the distribution of body mass is
      more predictive of SSI than the absolute BMI and deserves attention in
      preoperative evaluation.

PMID- 22146286
TI  - Lumbar total disc replacement impingement sensitivity to disc height distraction,
      spinal sagittal orientation, implant position, and implant lordosis.
AB  - STUDY DESIGN: A 3-dimensional finite element model of 2 lumbar motion segments
      (L4-L5 and L5-S1) was used to evaluate the sensitivity of lumbar total disc
      replacement (TDR) impingement to disc height distraction, spinal sagittal
      orientation, implant position, and implant lordosis. The models were implanted
      with a mobile-bearing TDR and exposed to simulated sagittally balanced erect
      posture. OBJECTIVE: The objective of this study was to determine the sensitivity
      of TDR impingement to disc height distraction, implant lordotic angle, implant
      anterior-posterior position, and spinal orientation relative to the horizon.
      SUMMARY OF BACKGROUND DATA: TDR has the potential to replace fusion as the "gold
      standard" for treatment of painful degenerative disc disease. However,
      complications after TDR have been associated with device impingement and
      accelerated polyethylene wear. METHODS: A previously developed finite element
      model of the lumbar spine was altered to include implantation of a mobile-bearing
      TDR. A series of sensitivity analyses was performed to determine impingement
      risk. Specifically, spinal orientation, disc height distraction, footplate
      lordotic angle, and anterior-posterior position were evaluated. RESULTS:
      Generally, TDR tended to result in an increase in extension rotation and facet
      contact force during simulated erect posture when compared with the intact
      models. Impingement risk was sensitive to all of the tested parameters.
      CONCLUSION: The data from this study indicate that lumbar mobile-bearing TDR
      impingement is sensitive to disc height distraction, anterior-posterior position,
      implant lordosis, and spinal sagittal orientation. TDR impingement risk can be
      minimized by choosing an implant with an appropriate amount of lordosis, not
      overdistracting the disc space, and taking care not to place the implant too far
      anterior or posterior.

PMID- 22146287
TI  - The burden of chronic low back pain: clinical comorbidities, treatment patterns,
      and health care costs in usual care settings.
AB  - STUDY DESIGN: Retrospective analysis of an insurance claims database. OBJECTIVE:
      To examine the comorbidities, treatment patterns, health care resource
      utilization, and direct medical costs of patients with chronic low back pain
      (CLBP) in clinical practice. SUMMARY OF BACKGROUND DATA: Although the
      socioeconomic impact of CLBP is substantial, characterization of comorbidities,
      pain-related pharmacotherapy, and health care resource use/costs of patients with
      CLBP relative to non-CLBP controls have been infrequently documented. METHODS:
      Using the LifeLink Health Plan Claims Database (IMS Health Inc., Watertown, MA),
      patients with CLBP, defined using the International Classification of Diseases,
      Ninth Revision, Clinical Modification, were identified and matched (age, sex, and
      region) with non-CLBP individuals. Comorbidities, pain-related pharmacotherapy,
      and health care service use/costs (pharmacy, outpatient, inpatient, total) were
      compared for the 2 groups during 2008. RESULTS: A total of 101,294 patients with
      CLBP and controls were identified (55% women; mean age was 47.2 +/- 11.6 years).
      Relative to controls, patients with CLBP had a greater comorbidity burden
      including a significantly higher (P < 0.0001) frequency of musculoskeletal and
      neuropathic pain conditions and common sequelae of pain such as depression (13.0%
      vs. 6.1%), anxiety (8.0% vs. 3.4%), and sleep disorders (10.0% vs. 3.4%). Pain
      related pharmacotherapy was significantly greater (P < 0.0001) among patients
      with CLBP including opioids (37.0% vs. 14.8%; P < 0.0001), nonsteroidal anti
      inflammatory drugs (26.2% vs. 9.6%; P < 0.0001), and tramadol (8.2% vs. 1.2%; P <
      0.0001). Prescribing of "adjunctive" medications for treating conditions
      associated with pain (i.e., depression, anxiety, and insomnia) was also
      significantly greater (P < 0.0001) among patients with CLBP; 36.3% of patients
      received combination therapy. Health care costs were significantly higher in the
      CLBP cohort (P < 0.0001), reflecting greater resource utilization. Total direct
      medical costs were estimated at $8386 +/- $17,507 in the CLBP group and $3607 +/-
      $10,845 in the control group; P < 0.0001). CONCLUSION: Patients with CLBP are
      characterized by greater comorbidity and economic burdens compared with those
      without CLBP. This economic burden can be attributed to greater prescribing of
      pain-related medications and increased health resource utilization.

PMID- 22146288
TI  - Sequential damage assessment of the different components of the posterior
      ligamentous complex after magnetic resonance imaging interpretation: prospective
      study 74 traumatic fractures.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To study whether there is a
      sequential pattern in the posterior ligamentous complex (PLC) rupture caused by
      deforming traumatic forces by analyzing magnetic resonance (MR) images in a
      consecutive prospective cohort of patients with traumatic vertebral fracture.
      SUMMARY OF BACKGROUND DATA: PLC plays an important role in vertebral stability.
      However, the sequence in which the different components of the PLC tear, in the
      face of traumatic forces, has not been yet described. METHODS: Prospective study
      of 74 consecutive vertebral acute traumatic fractures analyzed using radiography
      and magnetic resonance imaging (MRI) (FS-T2-w/short-tau inversion-recovery [STIR]
      sequences). Fracture morphology was classified according to the AO
      classification. Integrity of each PLC component-facet capsules, interspinous
      ligament (ISL), supraspinous ligament (SSL), and ligamentum flavum (LF)-was
      assessed and classified as intact, edema, or disruption. ISL edema was further
      subdivided depending on the extension (>50%/<50%). We analyzed the association
      between MRI signal and the AO progressive scale of morphological damage. RESULTS:
      AO type A1/A2 fractures associated with only facet distraction. A3 fractures
      showed additional ISL edema, usually less than 50%, with neither SSL nor LF
      disruption. Type B1 fractures associated with facet distraction, ISL edema or
      disruption, and low rate of SSL/LF disruptions; B2 fractures increased SS/LF
      disruption rates. Type C fractures associated with facet fracture or dislocation
      and ISL, SSL, or LF complete rupture. We found high association (P < 0.001)
      between AO progressive scale and MRI signal. MRI analysis showed that posterior
      distraction forces begin in the facets and extend throughout the ISL, starting at
      its posterosuperior margin (finally disinserting the SSL superiorly) and
      traveling diagonally toward anteroinferior border, finally tearing the LF.
      CONCLUSION: MR images correlated with AO progressive scale of morphological
      damage, which showed a progressive orderly rupture sequence among the different
      PLC components as traumatic forces increased.

PMID- 22146289
TI  - Feasibility of using short message service to collect pain outcomes in a low back
      pain clinical trial.
AB  - STUDY DESIGN: Observational study nested within a randomized controlled trial.
      OBJECTIVE: To evaluate the feasibility of using short message service (SMS)
      within a clinical trial of low back pain. SUMMARY OF BACKGROUND DATA:
      Technological advances have transformed communication technologies and opened the
      way for their use in clinical studies. SMSs have been tested for use in data
      collection for different patient groups, but little is known about use of this
      technology in low back pain research. METHODS: Trial participants who owned a
      mobile phone and knew how to send SMS messages were included in the study. The
      participants were sent an SMS message asking them to rate their average pain,
      once a month for 12 consecutive months. Response rates during the year were
      calculated, and regression analyses were used to explore factors associated with
      phone ownership and response rates. RESULTS: Of the 133 participants in the
      trial, 105 (61.1%) had mobile phones and 97 (56.4%) knew how to use SMS. The
      regression analyses showed that older patients were less likely to own a mobile
      phone (P < 0.000). Response rates to SMS alone during the 12 months ranged from
      54.8% to 74.2%, and for SMS supplemented with phone interviews ranged from 91.5%
      to 99%. The median (interquartile range) number of the scheduled 12 assessments
      completed by SMS per patient was 9 (interquartile range, 5-11). The Poisson
      regression revealed no significant effect for any of the predictors studied: age,
      sex, education level, and pain level at baseline and after treatment (P >= 0.16).
      CONCLUSION: SMS supplemented with phone interviews, but not SMS alone, is a
      feasible option to collect simple data within a back pain clinical trial setting.

PMID- 22146290
TI  - Gender difference in association between low back pain and metabolic syndrome:
      locomotive syndrome and health outcome in Aizu cohort study (LOHAS).
AB  - STUDY DESIGN: Cross-sectional survey. OBJECTIVE.: To investigate the relationship
      between low back pain (LBP) and metabolic syndrome (Mets) in community-based
      Japanese subjects. SUMMARY OF BACKGROUND DATA.: Relatively few reports have
      demonstrated a relationship between general pain and Mets, and none have
      addressed the relationship between LBP and Mets. METHODS: This study enrolled
      2650 people from among residents aged 40 to 74 years in Tadami and Minamiaizu,
      Fukushima, Japan, who participated in health checkups conducted in 2008. LBP was
      defined as lower back pain continuing for more than 24 hours and severe enough to
      merit treatment, or it was based on clinical prediction rules from the clinical
      diagnosis support tool to identify patients with lumbar spinal stenosis. Mets was
      defined according to the Japanese criteria recommended by the Japanese Society of
      Internal Medicine. Prevalence of Mets was recorded for subjects with and without
      LBP. The relationship between LBP and Mets was investigated, using a generalized
      linear model. With LBP as the main explanatory variable and Mets as the outcome
      variable, risk ratios of Mets were calculated for men and women. RESULTS: In this
      study, we analyzed a total of 1395 subjects. In men, the prevalence of Mets was
      21.2% in those without LBP and 24.7% in those with LBP. In women, the prevalence
      of Mets was 12.4% in those without LBP and 23.7% in those with LBP. After
      adjusting for factors such as age, body mass index, occupational status, SF-36
      mental health, and physical activity level, no relationship was noted between LBP
      and Mets in men. However, in women, the risk ratio for Mets in subjects with LBP
      compared with those without LBP was 1.5 (95% confidence interval, 1.0-2.1).
      CONCLUSION: We observed a tendency toward higher prevalence of Mets among those
      with LBP than among those without it in women, but not in men.

PMID- 22146291
TI  - Should symptomatic iliac screws be electively removed in adult spinal deformity
      patients fused to the sacrum?
AB  - STUDY DESIGN: Retrospective, single-institution review of adult deformity
      patients who underwent iliac screw (IS) removal placed during fusion to the
      sacrum. OBJECTIVE: To demonstrate whether IS removal offered benefit in terms of
      hip/buttock pain overlying the IS and whether IS could be removed without
      significant complications. SUMMARY OF BACKGROUND DATA: ISs are effective at
      countering cantilever forces imparted on sacral pedicle screws. Despite the
      efficacy of IS fixation, pain or implant prominence can lead to elective IS
      removal. There has been no study about IS removal in adult spinal deformity
      patients. METHODS: A total of 395 consecutive walking adult spinal deformity
      patients fused to the sacrum with IS fixation and minimum 2-year follow-up met
      study inclusion criteria. Clinical/radiographical data were analyzed. Because
      there is no validated pain outcomes instrument specific to this situation, an 8
      question IS removal questionnaire was designed and used for the sole purpose of
      this inquiry, within which a universally accepted numeric rating scale for pain
      was included. RESULTS.: Twenty-four of 395 (6.1%) patients (2 men and 22 women)
      with mean age of 50.5 +/- 10.8 years underwent elective IS removal at mean 2.6 +/
      1.3 years from index surgery. Mean follow-up from initial surgery was 6.3 +/-
      4.0 years. Symptoms included hip/buttock pain in all 24 patients and IS
      prominence in 5 patients (20.8%). Screw removal was bilateral in 18 (75%)
      patients and unilateral in 6 (25%) patients. Using a numeric rating pain scale (0
      10), hip/buttock pain improved after IS removal: preoperative 6.9 +/- 1.8,
      postoperative 2.0 +/- 2.7 (P < 0.05). Patients reported hip/buttock symptoms post
      IS removal as "much improved" (78.3%), "somewhat improved" (8.7%), and
      "unchanged" (13.0%). Two of 24 (8.3%) patients sustained complications from IS
      removal (wound infection, n = 1; coronal/sagittal imbalance, n = 1). Presented
      with the same set of circumstances, 22 of 24 (91.7%) patients would have their IS
      removed again, including one of the patients who had a complication. CONCLUSION:
      Of 395 consecutive walking patients who had ISs placed during fusion to the
      sacrum for adult spinal deformity, 24 (6.1%) underwent elective removal. Patients
      had a statistically significant improvement in hip/buttock pain after IS removal,
      and a low prevalence of complications after the procedure was observed.

PMID- 22146294
TI  - Does IGRT ensure target dose coverage of head and neck IMRT patients?
AB  - PURPOSE: To determine if image-guided radiotherapy (IGRT) ensures dose coverage
      to the target, and to assess the dosimetric impact of anatomic changes using
      megavoltage cone-beam CT (MVCBCT) for patient positioning during head and neck
      IMRT. METHODS AND MATERIALS: Forty-eight MVCBCT from 10 head and neck IMRT/IGRT
      patients were analyzed off-line. Target volumes and organs at risk (OARs)
      contours delineated on CT were transferred and adjusted on MVCBCT images. Each
      MVCBCT was processed to allow dose recalculation, resulting in 469 dose-volume
      histograms (DVHs). The concept of dosimetric latitude was introduced to provide a
      clinical perspective. RESULTS: MVCBCT target DVHs showed a moderate level of
      difference in D95 (dose to >=95% of volume), generally less than a 5% difference
      from the planned dose. Delivered-dose increases to the spinal cord and brainstem
      showed no apparent time trend. The 4mm margin around OARs was a useful precaution
      to prevent exceeding critical dose thresholds. The parotid glands showed
      progressive increases in mean dose related to shrinkage of the external contours.
      CONCLUSION: IGRT repositioning ensured target volume coverage, but significant
      dose variations were observed for OARs. The dosimetric impact of anatomic changes
      during radiotherapy was of lesser importance than the effects of IGRT
      repositioning.

PMID- 22146295
TI  - High-frequency single-electron transport in a quasi-one-dimensional GaAs channel
      induced by surface acoustic waves.
AB  - We report on an experimental investigation of the direct current induced by
      transmitting a surface acoustic wave (SAW) with frequency 2.7 GHz through a quasi
      one-dimensional (1D) channel defined in a GaAs - AlGaAs heterostructure by a
      split gate, when the SAW wavelength was approximately equal to the channel
      length. At low SAW power levels the current reveals oscillatory behaviour as a
      function of the gate voltage with maxima between the plateaux of quantized 1D
      conductance. At high SAW power levels, an acoustoelectric current was observed at
      gate voltages beyond pinch-off. In this region the current displays a step-like
      behaviour as a function of the gate voltage (or of the SAW power) with the
      magnitude corresponding to the transfer of one electron per SAW cycle. We
      interpret this as due to trapping of electrons in the moving SAW-induced
      potential minima with the number of electrons in each minimum being controlled by
      the electron - electron interactions. As the number of electrons is reduced, the
      classical Coulomb charging energy becomes the Mott - Hubbard gap between two
      electrons and finally the system becomes a sliding Mott insulator with one
      electron in each well.

PMID- 22146293
TI  - Progress of molecular targeted therapies for prostate cancers.
AB  - Prostate cancer remains the most commonly diagnosed malignancy and the second
      leading cause of cancer-related deaths in men in the United States. The current
      standard of care consists of prostatectomy and radiation therapy, which may often
      be supplemented with hormonal therapies. Recurrence is common, and many develop
      metastatic prostate cancer for which chemotherapy is only moderately effective.
      It is clear that novel therapies are needed for the treatment of the malignant
      forms of prostate cancer that recur after initial therapies, such as hormone
      refractory (HRPC) or castration resistant prostate cancer (CRPC). With advances
      in understanding of the molecular mechanisms of cancer, we have witnessed
      unprecedented progress in developing new forms of targeted therapy. Several
      targeted therapeutic agents have been developed and clinically used for the
      treatment of solid tumors such as breast cancer, non-small cell lung cancer, and
      renal cancer. Some of these reagents modulate growth factors and/or their
      receptors, which are abundant in cancer cells. Other reagents target the
      downstream signal transduction, survival pathways, and angiogenesis pathways that
      are abnormally activated in transformed cells or metastatic tumors. We will
      review current developments in this field, focusing specifically on treatments
      that can be applied to prostate cancers. Finally we will describe aspects of the
      future direction of the field with respect to discovering biomarkers to aid in
      identifying responsive prostate cancer patients.

PMID- 22146296
TI  - Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal
      cells via non-canonical pathway.
AB  - The efficient induction of cardiomyocyte differentiation from embryonic stem (ES)
      cells is crucial for cardiac regenerative medicine. Although Wnts play important
      roles in cardiac development, complex questions remain as to when, how and what
      types of Wnts are involved in cardiogenesis. We found that Wnt2 was strongly up
      regulated during cardiomyocyte differentiation from ES cells. Therefore, we
      investigated when and how Wnt2 acts in cardiogenesis during ES cell
      differentiation. Wnt2 was strongly expressed in the early developing murine
      heart. We applied this embryonic Wnt2 expression pattern to ES cell
      differentiation, to elucidate Wnt2 function in cardiomyocyte differentiation.
      Wnt2 knockdown revealed that intrinsic Wnt2 was essential for efficient
      cardiomyocyte differentiation from ES cells. Moreover, exogenous Wnt2 increased
      cardiomyocyte differentiation from ES cells. Interestingly, the effects on
      cardiogenesis of intrinsic Wnt2 knockdown and exogenous Wnt2 addition were
      temporally restricted. During cardiomyocyte differentiation from ES cells, Wnt2
      didn't activate canonical Wnt pathway but utilizes JNK/AP-1 pathway which is
      required for cardiomyocyte differentiation from ES cells. Therefore we conclude
      that Wnt2 plays strong positive stage-specific role in cardiogenesis through non
      canonical Wnt pathway in murine ES cells.

PMID- 22146297
TI  - A differentially selective sensor with fluorescence turn-on response to Zn2+ and
      dual-mode ratiometric response to Al3+ in aqueous media.
AB  - A novel quinoline-coumarin (QC) fluoroionophore conjugated by means of a
      triazolyl-pyrrolidinyl linker exhibits differential dual selectivity for Zn(2+)
      and Al(3+) in mixed media. QC acts as a turn on fluorescence sensor for Zn(2+)
      while exhibiting overall ratiometric selectivity for Al(3+) in aqueous media.
      Moreover, QC exhibited preferential second mode of selectivity for Al(3+) as it
      ratiometrically displaces Zn(2+) from the [QC + Zn(2+)] complex.

PMID- 22146298
TI  - Correlation of eigenstates in the critical regime of quantum Hall systems.
AB  - We extend the multifractal analysis of the statistics of critical wave functions
      in quantum Hall systems by calculating numerically the correlations of local
      amplitudes corresponding to eigenstates at two different energies. Our results
      confirm multifractal scaling relations which are different from those occurring
      in conventional critical phenomena. The critical exponent corresponding to the
      typical amplitude, [Formula: see text], gives an almost complete characterization
      of the critical behaviour of eigenstates, including correlations. Our results
      support the interpretation of the local density of states being an order
      parameter of the Anderson transition.

PMID- 22146299
TI  - Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional
      regulatory complex.
AB  - Recruitment of cofactors to specific DNA sites is integral for specificity in
      gene regulation. As a model system, we examined how targeting and transcriptional
      control of the sulfur metabolism genes in Saccharomyces cerevisiae is governed by
      recruitment of the transcriptional co-activator Met4. We developed genome-scale
      approaches to measure transcription factor (TF) DNA-binding affinities and
      cofactor recruitment to >1300 genomic binding site sequences. We report that
      genes responding to the TF Cbf1 and cofactor Met28 contain a novel 'recruitment
      motif' (RYAAT), adjacent to Cbf1 binding sites, which enhances the binding of a
      Met4-Met28-Cbf1 regulatory complex, and that abrogation of this motif
      significantly reduces gene induction under low-sulfur conditions. Furthermore, we
      show that correct recognition of this composite motif requires both non-DNA
      binding cofactors Met4 and Met28. Finally, we demonstrate that the presence of an
      RYAAT motif next to a Cbf1 site, rather than Cbf1 binding affinity, specifies
      Cbf1-dependent sulfur metabolism genes. Our results highlight the need to examine
      TF/cofactor complexes, as novel specificity can result from cofactors that lack
      intrinsic DNA-binding specificity.

PMID- 22146300
TI  - Overexpression limits of fission yeast cell-cycle regulators in vivo and in
      silico.
AB  - Cellular systems are generally robust against fluctuations of intracellular
      parameters such as gene expression level. However, little is known about
      expression limits of genes required to halt cellular systems. In this study,
      using the fission yeast Schizosaccharomyces pombe, we developed a genetic 'tug-of
      war' (gTOW) method to assess the overexpression limit of certain genes. Using
      gTOW, we determined copy number limits for 31 cell-cycle regulators; the limits
      varied from 1 to >100. Comparison with orthologs of the budding yeast
      Saccharomyces cerevisiae suggested the presence of a conserved fragile core in
      the eukaryotic cell cycle. Robustness profiles of networks regulating cytokinesis
      in both yeasts (septation-initiation network (SIN) and mitotic exit network
      (MEN)) were quite different, probably reflecting differences in their physiologic
      functions. Fragility in the regulation of GTPase spg1 was due to dosage imbalance
      against GTPase-activating protein (GAP) byr4. Using the gTOW data, we modified a
      mathematical model and successfully reproduced the robustness of the S. pombe
      cell cycle with the model.

PMID- 22146302
TI  - Winner takes all in a race for cell fate.

PMID- 22146301
TI  - Temporal competition between differentiation programs determines cell fate
      choice.
AB  - Multipotent differentiation, where cells adopt one of several possible fates,
      occurs in diverse systems ranging from bacteria to mammals. This decision-making
      process is driven by multiple differentiation programs that operate
      simultaneously in the cell. How these programs interact to govern cell fate
      choice is poorly understood. To investigate this issue, we simultaneously
      measured activities of the competing sporulation and competence programs in
      single Bacillus subtilis cells. This approach revealed that these competing
      differentiation programs progress independently without cross-regulation before
      the decision point. Cells seem to arrive at a fate choice through differences in
      the relative timing between the two programs. To test this proposed dynamic
      mechanism, we altered the relative timing by engineering artificial cross
      regulation between the sporulation and competence circuits. Results suggest a
      simple model that does not require a checkpoint or intricate cross-regulation
      before cellular decision-making. Rather, cell fate choice appears to be the
      outcome of a 'molecular race' between differentiation programs that compete in
      time, providing a simple dynamic mechanism for decision-making.

PMID- 22146303
TI  - Hyperbaric oxygen therapy (1.5 ATA) in treating sports related TBI/CTE: two case
      reports.
AB  - Despite adequate evidence, including randomized controlled trials; hyperbaric
      oxygen is not yet recognized as efficacious for treating various forms of brain
      injury, specifically traumatic brain injury. Political-economic issues have kept
      this benign therapy from being widely adopted despite the lack of viable
      alternatives. Two football players with TBI/CTE are herewith shown to benefit
      from being treated with hyperbaric oxygen as documented by neurocognitive
      examinations and functional brain imaging, in one case treatment commenced
      decades after the brain injury. Perhaps the interest in HBOT by those
      participating in high-risk sports will help expand this orphan therapy into
      mainstream medicine.

PMID- 22146304
TI  - Hyperbaric oxygen for stroke treatment.
AB  - This is an editorial for the inauguration of the Medical Gas Research and
      addresses a particular issue of using hyperbaric oxygen for stroke treatment.

PMID- 22146305
TI  - Pulmonary embolism in a patient with apical ballooning syndrome.

PMID- 22146309
TI  - Glucocorticoid acts on a putative G protein-coupled receptor to rapidly regulate
      the activity of NMDA receptors in hippocampal neurons.
AB  - Glucocorticoids (GCs) have been demonstrated to act through both genomic and
      nongenomic mechanisms. The present study demonstrated that corticosterone rapidly
      suppressed the activity of N-methyl-D-aspartate (NMDA) receptors in cultured
      hippocampal neurons. The effect was maintained with corticosterone conjugated to
      bovine serum albumin and blocked by inhibition of G protein activity with
      intracellular GDP-beta-S application. Corticosterone increased GTP-bound G(s)
      protein and cyclic AMP (cAMP) production, activated phospholipase Cbeta(3) (PLC
      beta(3)), and induced inositol-1,4,5-triphosphate (IP(3)) production. Blocking
      PLC and the downstream cascades with PLC inhibitor, IP(3) receptor antagonist,
      Ca(2+) chelator, and protein kinase C (PKC) inhibitors prevented the actions of
      corticosterone. Blocking adenylate cyclase (AC) and protein kinase A (PKA) caused
      a decrease in NMDA-evoked currents. Application of corticosterone partly reversed
      the inhibition of NMDA currents caused by blockage of AC and PKA.
      Intracerebroventricular administration of corticosterone significantly suppressed
      long-term potentiation (LTP) in the CA1 region of the hippocampus within 30 min
      in vivo, implicating the possibly physiological significance of rapid effects of
      GC on NMDA receptors. Taken together, our results indicate that GCs act on a
      putative G protein-coupled receptor to activate multiple signaling pathways in
      hippocampal neurons, and the rapid suppression of NMDA activity by GCs is
      dependent on PLC and downstream signaling.

PMID- 22146310
TI  - The anorexigenic cytokine ciliary neurotrophic factor stimulates POMC gene
      expression via receptors localized in the nucleus of arcuate neurons.
AB  - Ciliary neurotrophic factor (CNTF) is a neural cytokine that reduces appetite and
      body weight when administrated to rodents or humans. We have demonstrated
      recently that the level of CNTF in the arcuate nucleus (ARC), a key hypothalamic
      region involved in food intake regulation, is positively correlated with
      protection against diet-induced obesity. However, the comprehension of the
      physiological significance of neural CNTF action was still incomplete because
      CNTF lacks a signal peptide and thus may not be secreted by the classical
      exocytosis pathways. Knowing that CNTF distribution shares similarities with that
      of its receptor subunits in the rat ARC, we hypothesized that CNTF could exert a
      direct intracrine effect in ARC cells. Here, we demonstrate that CNTF, together
      with its receptor subunits, translocates to the cell nucleus of anorexigenic POMC
      neurons in the rat ARC. Furthermore, the stimulation of hypothalamic nuclear
      fractions with CNTF induces the phosphorylation of several signaling proteins,
      including Akt, as well as the transcription of the POMC gene. These data strongly
      suggest that intracellular CNTF may directly modulate POMC gene expression via
      the activation of receptors localized in the cell nucleus, providing a novel
      plausible mechanism of CNTF action in regulating energy homeostasis.

PMID- 22146311
TI  - CHD1L: a new candidate gene for congenital anomalies of the kidneys and urinary
      tract (CAKUT).
AB  - BACKGROUND: Recently, we identified a microduplication in chromosomal band 1q21.1
      encompassing the CHD1L/ALC1 gene encoding a chromatin-remodelling enzyme in
      congenital anomalies of the kidneys and urinary tract (CAKUT) patient. METHODS:
      To explore the role of CHD1L in CAKUT, we screened 85 CAKUT patients for
      mutations in the CHD1L gene and performed functional analyses of the three
      heterozygous missense variants detected. In addition, we quantitatively
      determined CHD1L expression in multiple human fetal and adult tissues and
      analysed expression of CHD1L protein in human embryonal, adult and hydronephrotic
      kidney sections. RESULTS: Two of three novel heterozygous missense variants
      identified in three patients were not found in >400 control chromosomes. All
      variants lead to amino acid substitutions in or near the CHD1L macro domain, a
      poly-ADP-ribose (PAR)-binding module interacting with PAR polymerase 1 (PARP1),
      and showed decreased interaction with PARP1 by pull-down assay of transfected
      cell lysates. Quantitative messenger RNA analysis demonstrated high CHD1L
      expression in human fetal kidneys, and levels were four times higher than in
      adult kidneys. In the human embryo at 7-11 weeks gestation, CHD1L immunolocalized
      in the early ureteric bud and the S- and comma-shaped bodies, critical stages of
      kidney development. In normal postnatal sections, CHD1L was expressed in the
      cytoplasm of tubular cells in all tubule segments. CHD1L expression appeared
      higher in the hydronephrotic kidney of one patient with a hypofunctional CHD1L
      variant than in normal kidneys, recapitulating high fetal levels. CONCLUSION: Our
      data suggest that CHD1L plays a role in kidney development and may be a new
      candidate gene for CAKUT.

PMID- 22146312
TI  - [Cancer before age 40 in France].
AB  - Cancer is a rare pathology before the age of 40: a total of 14,000 new cases have
      been diagnosed in patients under age 40 in 2005, 1,700 under age 15 and 12,500 in
      the age-group of 15 to 39, this represents 4% of the cancers diagnosed in 2005.
      The number of deaths is small: in 2008, 2,235 patients died before age 40 in
      France, 246 under age 15 and 1,989 between age 15 and 39; this corresponds to 1%
      of the cancer deaths in 2008. The incidence increased between 1980 and 2005, both
      in the population aged 0 to 14 and in the population aged 15 to 39. Overall,
      cancer mortality has been decreasing for more than 25 years. The only increase in
      mortality is observed for brain tumours in children. The overall incidence
      increase is mostly due to the extension of screening coverage and to improvements
      in diagnostic procedures. The decrease observed for cervix cancer and lung cancer
      in men demonstrates the efficacy of screening and of tobacco smoking prevention.
      The mortality decrease is explained both by improved treatments and by the
      decreased incidence of some types of cancer. The increasing brain tumours
      mortality in children is worrying.

PMID- 22146313
TI  - B-cell depleting agents for ANCA vasculitides: a new therapeutic approach.
AB  - Vasculitides associated with anti-neutrophil cytoplasmic antibody (ANCA) serum
      positivity affecting small and medium-sized vessels are defined as ANCA
      associated vasculitis (AAV). Glomerulonephritis in AAV is characterized by focal
      necrosis, crescent formation, and few or no immunoglobulin deposits. In vitro and
      animal evidence suggests that ANCA play a pathogenic role in AAV. Specific gene
      expression signatures are reported to predict long-term prognosis in AAV,
      suggesting the possibility of individualizing therapy and identifying new
      therapeutic targets. Although immunosuppressants and glucocorticoids are the
      cornerstone of AAV therapy, results from two recent randomized controlled trials
      have shown the non-inferiority of rituximab, compared with cyclophosphamide, for
      the induction of remission in patients with severe AAV. In fact, in April 2011,
      the US Food and Drug Administration (FDA) approved rituximab, combined with
      glucocorticoids, as a front-line therapy for adult patients with granulomatosis
      with polyangiitis (GPA; Wegener's granulomatosis) or microscopic polyangiitis.
      This new indication for rituximab provided the first ever FDA-approved therapy
      for these two diseases and the first alternative to cyclophosphamide for the
      treatment of severe disease in almost 40years. However, issues regarding the use
      of maintenance therapy after rituximab, the concurrent use of cyclophosphamide
      and the toxicity of rituximab remain unanswered and should be clarified in
      ongoing and future randomized controlled trials.

PMID- 22146314
TI  - End-stage renal disease and cardiomyopathy in children:  cardiac effects of renal
      transplantation.
AB  - BACKGROUND: The occurrence and progression of cardiomyopathy is well known in
      patients with end-stage renal disease (ESRD). However, the feasibility of renal
      transplantation in the setting of cardiac dysfunction and the effect of renal
      transplantation on this progression remain poorly studied in pediatric patients.
      METHODS: A single-center, retrospective review of pediatric renal transplants
      between January 1, 2001, and December 31, 2010, was conducted. Six children with
      ESRD and severe systolic dysfunction underwent renal transplantation. Clinical
      data were collected and compared for the pretransplant, peritransplant, and
      posttransplant periods. RESULTS: Nutritional support, dialysis, and chronic
      kidney disease and heart failure therapy led to improved cardiac function before
      transplantation (ejection fraction 28.8%+/-9.6% vs. 44.4%+/-11.5%; fractional
      shortening 12.7%+/-5.1% vs. 23.6%+/-6.2%); however, normal systolic function was
      not achieved before transplantation in any patient. After transplantation, two
      patients had normalization of systolic function by hospital discharge, while the
      systolic function of the remaining four patients normalized during the first
      posttransplant year. Mean ejection fraction 1 year posttransplant was 22 units
      greater than before transplant. All patients experienced excellent allograft
      function in the peritransplant period. Mean estimated creatinine clearance 1 year
      posttransplant was 93.2+/-33.3 mL/min/1.73 m(2). CONCLUSIONS: Renal
      transplantation can be performed safely in children with ESRD and severe systolic
      dysfunction. After transplantation, systolic function continues to improve and
      may reach normal levels during the first posttransplant year. The presence of
      severe systolic dysfunction in pediatric dialysis patients should not deter
      referral for renal transplantation.

PMID- 22146315
TI  - Induced anti-non gal antibodies in human xenograft recipients.
AB  - Anti-non gal antibodies are produced in xenograft recipients against multiple
      xenogeneic antigens. Studies in monkeys transplanted with pig organs lacking
      alpha-gal epitopes have suggested that anti-non gal antibodies mediate acute and
      chronic rejection of xenografts. This overview describes studies of these
      antibodies in patients who received xenografts and includes (1) an ovarian
      carcinoma patient receiving three intraperitoneal infusions of mouse fibroblasts
      in a gene therapy study, (2) orthopedic patients with torn anterior cruciate
      ligament replaced by a ligament made of pig patellar tendon, and (3) diabetic
      patients receiving fetal pig islet cell clusters xenograft together with a kidney
      allograft. Anti-non gal antibodies were found to be continuously produced as long
      as the xenograft was present in the recipient and were directed against a large
      number of pig proteins. Monitoring the immune response in the recipient of mouse
      fibroblasts indicated that the production of anti-non gal antibodies is much
      slower than that of the anti-Gal antibody, suggesting that they are generated by
      multiple B-cell clones, each initially comprising relatively few cells. Potent
      immunosuppression to prevent allograft rejection does not fully inhibit the
      production of anti-non gal antibodies. Much of this antibody response seems to be
      due to the differences in amino acid sequences between pig and human orthologous
      proteins as a result of evolutionary mutations. Overcoming the anti-non gal
      antibody barrier will require immunosuppressive agents that preferentially
      inhibit this immune response while maintaining protection against pathogens, or
      alternatively development of methods for induction of immune tolerance to
      xenogeneic pig antigens.

PMID- 22146316
TI  - The phase diagram and hidden order for generalized spin ladders.
AB  - We investigate the phase diagram of antiferromagnetic spin ladders with
      additional exchange interactions on diagonal bonds by variational and numerical
      methods. These generalized spin ladders interpolate smoothly between the
      [Formula: see text] chain with competing nn and nnn interactions, the [Formula:
      see text] chain with alternating exchange and the antiferromagnetic (AF) S = 1
      chain. The Majumdar - Ghosh ground states are formulated as matrix product states
      and are shown to exhibit the same type of hidden order as the AF S = 1 chain.
      Generalized matrix product states are used for a variational calculation of the
      ground state energy and the spin and string correlation functions. Numerical
      (Lanczos) calculations of the energies of the ground state and of the low-lying
      excited states are performed, and compare reasonably with the variational
      approach. Our results support the hypothesis that the dimer and Majumdar - Ghosh
      points are in the same phase as the AF S = 1 chain.

PMID- 22146317
TI  - Transcriptional regulation of the human Raver2 ribonucleoprotein gene.
AB  - Raver2 is a putative modulator of the activity of the polypyrimidine-tract
      binding protein (PTB), one of the most intensively studied splicing repressors.
      Little is known about Raver2 expression, and all current data is from mice where
      it shows tissue specificity. In the present study, by comparing Raver2 transcript
      expression in human and mouse tissues, we found that human Raver2 is ubiquitously
      expressed in adult tissues. In order to investigate human Raver2 transcription
      regulation, we identified and characterized a putative promoter region in a
      1000bp region upstream of the transcription starting site of the gene. Dual
      luciferase reporter assays demonstrated that this region had promoter activity
      conferred by the first 160bp. By mutagenic analyses of putative cis-acting
      regulatory sequences, we identified an individual site that decreased the
      promoter activity by up to 40% when mutated. Together, our results suggest that
      regulation of human Raver2 expression involves TATA-less transcriptional
      activity.

PMID- 22146318
TI  - Identification and validation of Asteraceae miRNAs by the expressed sequence tag
      analysis.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that play a vital role in
      the regulation of gene expression. Despite their identification in hundreds of
      plant species, few miRNAs have been identified in the Asteraceae, a large family
      that comprises approximately one tenth of all flowering plants. In this study, we
      used the expressed sequence tag (EST) analysis to identify potential conserved
      miRNAs and their putative target genes in the Asteraceae. We applied quantitative
      Real-Time PCR (qRT-PCR) to confirm the expression of eight potential miRNAs in
      Carthamus tinctorius and Helianthus annuus. We also performed qRT-PCR analysis to
      investigate the differential expression pattern of five newly identified miRNAs
      during five different cotyledon growth stages in safflower. Using these methods,
      we successfully identified and characterized 151 potentially conserved miRNAs,
      belonging to 26 miRNA families, in 11 genus of Asteraceae. EST analysis predicted
      that the newly identified conserved Asteraceae miRNAs target 130 total protein
      coding ESTs in sunflower and safflower, as well as 433 additional target genes in
      other plant species. We experimentally confirmed the existence of seven predicted
      miRNAs, (miR156, miR159, miR160, miR162, miR166, miR396, and miR398) in safflower
      and sunflower seedlings. We also observed that five out of eight miRNAs are
      differentially expressed during cotyledon development. Our results indicate that
      miRNAs may be involved in the regulation of gene expression during seed
      germination and the formation of the cotyledons in the Asteraceae. The findings
      of this study might ultimately help in the understanding of miRNA-mediated gene
      regulation in important crop species.

PMID- 22146319
TI  - MicroRNA-421 functions as an oncogenic miRNA in biliary tract cancer through down
      regulating farnesoid X receptor expression.
AB  - MicroRNAs (miRNAs) are involved in the development of most cancers. However, few
      studies have been conducted to determine their relationship to biliary tract
      cancer (BTC). Farnesoid X receptor (FXR) has been reported to be a tumor
      suppressor for hepatocellular carcinoma and breast cancer; but few studies have
      focused on its correlation with BTC. In this study, we identified miR-421 as a
      potential regulator of FXR expression. We found that their expression amount was
      inversely correlated as FXR was aberrantly down-regulated in both primary tumor
      specimens and cell lines; while miR-421 was significantly up-regulated. Ectopic
      expression of miR-421 significantly decreased FXR protein concentration in BTC
      cells and promoted cell proliferation, colony formation and migration in vitro.
      Furthermore, a decrease in miR-421 expression induced G(0)/G(1) cell cycle
      arrest. In conclusion, our study identified microRNA-421 functions as an oncomiR
      in BTC by targeting FXR. This finding may provide a novel therapeutic strategy
      for treatment of biliary tract cancer.

PMID- 22146320
TI  - Calorie restriction increases primordial follicle reserve in mature female
      chemotherapy-treated rats.
AB  - We assessed the effects of calorie restriction (CR)-mediated protection against
      chemotherapy damage on ovarian reserve. Forty-eight female Sprague-Dawley rats
      were randomly divided into four groups: the normal control group (NC group, fed
      ad libitum), the CR group (fed with 65% food intake of the NC group), the CTX
      group (injected with cyclophosphamide (CTX) and fed ad libitum), and the CR+CTX
      group (injected with CTX and fed with 65% food intake of the NC group). Ovarian
      reserve was examined by vaginal smears and follicle counting. SIRT1 is a
      deacetylase that is activated by a variety of stressors and targets
      transcriptional regulators including p53, NF-kappaB, FOXO1, 3, and 4, and the
      transcriptional regulator PGC-1alpha. The expression level of SIRT1, p53 and
      FOXO3a in the ovary was measured by western blot. CR did not interfere with
      estrous cycling but maintained estrous cycling in CTX-treated CR rats. The number
      of primordial follicles in the CR rats was comparable to the NC group, and CR+CTX
      group rats had more primordial follicles and primary follicles than the CTX
      group. SIRT1 expression in the ovary was higher in the CR group compared to the
      control group, and p53 level was lower in the CR group than that in the NC group.
      There is no significant difference in the expression level of FOXO3a between the
      CR group and the NC group. CONCLUSIONS: These results indicate that CR can
      increase the ovarian follicular reserve and reduce the CTX-induced ovarian
      damage, and CR positive effects may be due to its intervention in the transition
      from primordial to primary follicle, and its reduction of oxidative stress.

PMID- 22146321
TI  - Multiple sclerosis- diagnosis, management and prognosis.
AB  - BACKGROUND: Multiple sclerosis is the most common chronic disabling disease of
      the central nervous system in young adults. OBJECTIVE: This article summarises
      the diagnosis, management and prognosis of multiple sclerosis. DISCUSSION:
      Multiple sclerosis usually starts with an acute episode of neurological
      disturbance, termed a 'clinically isolated syndrome', followed by an illness
      phase punctuated by relapses and remissions which may transition after 10 years
      to a phase of progressive accumulation of disability without relapses. Fifteen to
      20% of patients will have a progressive course from the onset. There is
      significant interpatient variability in prognosis. The main diagnostic criteria
      are clinical, supported by investigations including magnetic resonance imaging
      and lumbar puncture and evoked potentials. First line disease modifying agents
      for relapsing remitting multiple sclerosis include interferon-beta and
      glatiramer. First line treatment for relapses is usually intravenous
      methylprednisolone for 3 days. Troublesome symptoms may include spasticity,
      parasthesias, tremor, erectile dysfunction, depression and anxiety, fatigue and
      pain. After excluding differential diagnoses, symptomatic management includes
      pharmacological agents, allied health consultation and continence strategies.
      Although pregnancy reduces disease activity, there is a higher risk of relapse in
      the postpartum period.

PMID- 22146322
TI  - Traumatic brain injury - long term care of patients in general practice.
AB  - BACKGROUND: Traumatic brain injury is a significant cause of disability
      worldwide. Patients with a traumatic brain injury may have a range of physical,
      mental, cognitive and social problems involving care from a general practitioner.
      OBJECTIVE: This article provides a summary of the available evidence for managing
      the common mental health, somatic and cognitive/behavioural issues associated
      with traumatic brain injury. DISCUSSION: The long term sequelae of traumatic
      brain injury pose a number of challenges for patients, their families and GPs.
      Common somatic complaints include seizures, headache, dizziness and sleep
      disturbance. Common mental health problems include depression, psychosis and
      anxiety. Cognitive and behavioural or personality changes can be significant and
      persist for some time following injury. Quality of life is closely predicted by
      return to the workforce and long term functional status is often linked to the
      severity of the injury. There is limited evidence for effective treatments of
      these sequelae and a need for more research. However, there are a number of
      proven treatments and an emerging understanding of the long term sequelae of
      traumatic brain injury.

PMID- 22146323
TI  - Motor neurone disease - caring for the patient in general practice.
AB  - BACKGROUND: Motor neurone disease is a neurodegenerative disease that leads to
      progressive disability - and eventually death - within 2-3 years. OBJECTIVE: This
      article describes the role of the general practitioner in caring for patients
      with motor neurone disease. DISCUSSION: The diagnosis of motor neurone disease
      relies on the presence of upper and lower motor neurone features. There is
      currently no pathognomic test for motor neurone disease and it largely remains a
      diagnosis of exclusion following an accurate clinical history, combined with
      basic screening blood investigations and structural imaging of the brain and
      spinal cord. Neuro-physiological studies may be useful as an ancillary diagnostic
      tool. Riluzole, an anti-glutamate agent, is the only medication shown to have a
      survival benefit in motor neurone disease and results in a slowing of disease
      progression by an estimated 3-6 months. Noninvasive ventilation may relieve
      symptoms related to respiratory insufficiency and prolong survival by up to 12
      months. A multidisciplinary approach to management has been shown to improve the
      quality of life for patients as well as survival. The GP is often the first point
      of contact when medical issues arise regarding management of disease related
      symptoms including sialorrhoea, dyspnoea, constipation and pain, through to
      percutaneous gastrostomy feeding tubes and maintenance of noninvasive
      ventilation. It is important to establish the patient's wishes for future care
      while they are still able to communicate easily.

PMID- 22146324
TI  - Frontotemporal dementia - features, diagnosis and management.
AB  - BACKGROUND: Frontotemporal dementia is the third or fourth most common form of
      dementia in the 45-65 years age group. It causes significant morbidity as well as
      a six to eightfold increase in mortality risk. OBJECTIVE: This article provides
      an overview of the pathophysiology of frontal lobe function and the genetics of
      frontotemporal dementia. It also summarises the clinical features, diagnosis and
      management of frontotemporal dementia. DISCUSSION: While the clinical
      presentation of frontotemporal dementia was described as early as the nineteenth
      century, recent advances in genetics have resulted in greater understanding of
      the pathophysiology of this disease. While imaging may support the diagnosis of
      frontotemporal dementia, it is essentially a clinical diagnosis based on the
      presence of typical clinical features and the findings of neuropsychological
      tests. Clinical management of frontotemporal dementia remains a challenge and is
      largely centred on behavioural management. Pharmacological agents such as
      selective serotonin reuptake inhibitors and antipsychotics may be helpful,
      although evidence to support their use is minimal.

PMID- 22146325
TI  - Lactational mastitis and breast abscess - diagnosis and management in general
      practice.
AB  - BACKGROUND: Lactational mastitis is common, affecting one in 5 breastfeeding
      women. As well as causing significant discomfort, it is a frequent reason for
      women to stop breastfeeding. OBJECTIVE: This article outlines an evidence based
      approach to the diagnosis and management of lactational breast infections in
      general practice. DISCUSSION: Lactational mastitis is usually bacterial in
      aetiology and can generally be effectively managed with oral antibiotics.
      Infections that do not improve rapidly require further investigation for breast
      abscess and nonlactational causes of inflammation, including the rare cause of
      inflammatory breast cancer. In addition to antibiotics, management of lactational
      breast infections include symptomatic treatment, assessment of the infant's
      attachment to the breast, and reassurance, emotional support, education and
      support for ongoing breastfeeding.

PMID- 22146326
TI  - Monomorphous papulopustular rash - a case study.

PMID- 22146327
TI  - ACEI associated angioedema - a case study and review.
AB  - BACKGROUND: Angioedema is an infrequent but potentially serious adverse effect of
      angiotensin converting enzyme inhibitors (ACEIs). OBJECTIVE: This article
      describes a case of ACEI associated angioedema and reviews important clinical
      features of the condition. DISCUSSION: The mechanism of ACEI associated
      angioedema is not allergic (histamine mediated), but rather due to an alteration
      of the balance of bradykinin and other vasodilator mediators. Onset may be
      delayed for weeks, months or years and episodes may be recurrent. Occasionally,
      airway obstruction may occur. Diagnosis is from history and physical examination;
      there is no specific diagnostic test. In contrast to allergic angioedema, ACEI
      associated angioedema is generally unresponsive to corticosteroids and
      antihistamines, although these agents are often used by convention. In the longer
      term, cessation of the ACEI is necessary to reduce the risk of recurrent
      episodes.

PMID- 22146328
TI  - Melanoma - improving diagnosis in general practice.
AB  - Australia is the world capital of melanoma and despite our best efforts to 'slip
      slop-slap' the incidence of melanoma continues to rise. In 2007, 10,342
      Australians were diagnosed with melanoma and 1,279 people died from the disease.

PMID- 22146329
TI  - Teaching medical students - ethical challenges.
AB  - AIM: To explore ethical challenges for general practitioners teaching medical
      students in urban general practice. Methods Semistructured face-to-face
      interviews with 60 urban general practice teachers with diverse teaching loads
      and practice demographics. Interview data were analysed following member checking
      of interview records. RESULTS: Participants identified concerns in relation to a
      number of areas including: student assessment and professionalism; teaching
      support from colleagues; patient consent and confidentiality; and the effects of
      teaching on consultation dynamics, patient satisfaction and patient care.
      Participants with smaller teaching loads and with full fee-paying patients were
      more likely to express concerns about involving students actively in
      consultations. DISCUSSION: General practice teachers should consider modelling
      seeking informed patient consent in difficult circumstances, while being mindful
      that patients may be reluctant to refuse or withdraw consent. Arguably students
      themselves should seek consent. General practitioners should consider maintaining
      the confidentiality of previously divulged patient information. Concerns about
      active student involvement in teaching consultations should be discussed with
      teaching colleagues from similar practice demographics, with reference to
      pertinent literature about patient attitudes to teaching.

PMID- 22146330
TI  - Australia's systems of primary healthcare - the need for improved coordination
      and implications for Medicare Locals.
AB  - BACKGROUND: In Australia, primary healthcare is largely delivered through two
      parallel systems: Medicare supported primary care delivered by fee-for-service
      general practitioners, and state funded and managed community health services.
      METHODS: Semistructured interviews with 18 GPs to investigate the current links
      between GPs and local primary healthcare providers. RESULTS: Barriers to links
      include: communication and information, access and availability of services, GP
      lack of awareness and understanding of services provided in the state funded
      sector, and lack of time to gain information. Discussion General practitioners
      reported dealing with more complex and challenging patients. However, this did
      not appear to increase their likelihood of engaging with state funded primary
      healthcare services in case management. Medicare Locals are a once-in-a
      generation chance to establish a genuinely coordinated and multidisciplinary
      primary healthcare sector. To be successful, Medicare Locals will need to bring
      together two parallel systems of care and improve integration and coordination.

PMID- 22146331
TI  - An online course in clinical education - experiences of Australian clinicians.
AB  - AIMS: We aimed to understand clinicians' experience of online training in the
      area of clinical education. METHODS: We conducted semistructured in-depth
      interviews with a purposive sample of 20 clinicians studying clinical education
      online. Interviews were transcribed verbatim into N-Vivo qualitative analysis
      software. Data were analysed against a template derived from open coding merged
      with a priori themes from a program logic model. RESULTS: Clinicians in this
      study found learning online convenient but there was a trade off between this
      convenience and developing an authentic online community of learners. Optional
      intensives were important for developing relationships with staff and other
      students. Clinicians faced significant time pressures when adding study to their
      busy workloads and lives. Protected study time, assistance with course fees,
      information technology support, facilitated discussion and a flexible approach to
      assignment submission dates were cited as useful. CONCLUSION: Clinicians can
      develop as educators online if given appropriate time and support.

PMID- 22146332
TI  - Moving with the times - familiarity versus formality in Australian general
      practice.
AB  - BACKGROUND: Forms of address between patients and general practitioners is an
      underexplored area which may influence productive dialogue within a consultation.
      This article aims to describe how Australian patients prefer to be addressed by
      their GP, how patients prefer to address their GP, and the factors influencing
      these preferences. METHODS: Twenty consecutive patients of 13 randomly selected
      GPs (n=260) were surveyed on preferences for use of names in consultations and
      the factors influencing these preferences. RESULTS: Ninety percent of patients
      prefer to be addressed by their first name. Thirty-five percent of patients
      prefer to call the GP by first name, 27% by title and last name, 21% by title
      only, and 10% by title and first name. A range of influencing factors was
      identified. DISCUSSION: These findings allow GPs to feel confident in addressing
      their patients informally. They indicate the diversity of patient preferences for
      addressing their GP and the factors influencing these choices.

PMID- 22146333
TI  - Family law matters - a guide for GPs.
AB  - BACKGROUND: General practitioners are regularly called upon to assist their
      patients in family law disputes. They are often served with a subpoena to produce
      their patient's file, or that of their children, and can be called upon to
      provide short reports regarding various health conditions of their patients.
      Doctors can also sometimes become witnesses in family law litigation and the time
      needed to participate is rarely compensated. OBJECTIVE This article aims to
      provide GPs with key information in relation to responding to a subpoena and the
      preparation of reports in family law matters. DISCUSSION: Careful preparation of
      subpoenas and reports by GPs who find themselves embroiled in the family law
      disputes of their patients can save significant time and costs to all involved.

PMID- 22146334
TI  - A partnership for health - working with schools to promote healthy lifestyle.
AB  - BACKGROUND: Childhood obesity is increasing in prevalence. Effective
      interventions are needed, including those promoting healthy lifestyle habits in
      children and adolescents. OBJECTIVE: This article describes the development and
      feasibility of a peer led health promotion program in a New South Wales high
      school and the role GPs can play in community based health promotion activities.
      DISCUSSION: The Students As Lifestyle Activists (SALSA) program was developed by
      general practitioners, a local community health organisation and a local high
      school. Preliminary evaluation suggests that a peer led approach is feasible,
      acceptable and valued by both students and staff.

PMID- 22146335
TI  - Academic posts at The University of Melbourne - 28 years of history.
AB  - General practice registrars have the opportunity to undertake an academic post
      during their training. This 12 month part time post provides an opportunity to
      train in various facets of the emerging area of primary care research. The
      Department of General Practice (DGP) at The University of Melbourne (UoM) has
      hosted academic registrars for the past 28 years. Over this time, some important
      changes have occurred.

PMID- 22146336
TI  - HoMER - an opportunity or threat to general practice research?
AB  - The National Health and Medical Research Council (NHMRC) Harmonisation of
      Multicentre Ethical Review (HoMER) project aims to implement a 'single ethical
      review', where the outcome of an ethical and scientific review by a single
      recognised Human Research Ethics Committee (HREC) will enable multiple
      institutions to decide whether or not to participate in a given study. The
      desired process will include agreement on time frames, authority of the reviewing
      HREC, respect among the jurisdictions, verification by independent organisations,
      and compliance with the national statement and relevant statutory and
      administrative frameworks. However, there appears to be little discourse on the
      implications for general practice research in the research community.

PMID- 22146337
TI  - Pathophysiologic and immunologic changes in a canine endotoxemia over a period of
      24 hours.
AB  - In this study, the pathophysiologic and immunologic parameters from a 24-hr of
      canine endotoxemia model by lipopolysaccharide (LPS) infusion were evaluated. For
      that, twelve healthy beagles received a continuous 24-hr IV infusion of low dose
      LPS (10 ug/kg/h, from Escherichia coli serotype O111:B4) dissolved in saline.
      Complete blood counts and serum biochemical analysis as well as histopathologic
      examination were performed to assess pathophysiologic changes such as neutrophil
      migration and organ injury. To evaluate immunologic parameters, the
      concentrations of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6
      and IL-10 were determined, and neutrophil activation was also evaluated based on
      cell surface expression of CD11b using flow cytometry analysis. As results,
      systemic signs of endotoxemia including fever, vomiting, and hemorrhagic diarrhea
      were observed within short time after LPS infusion. Severe leukopenia and
      increased fluorescent intensity of CD11b on neutrophils were observed at 3 hr
      while percent positive of CD11b was the maximum at 12 hr during the experiment.
      Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline
      phosphatase (ALP), lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK)
      concentrations increased markedly, and organ damage was confirmed on
      histopathologic examination. Plasma TNF-alpha peaked at 3 hr and decreased
      rapidly, while the concentrations of IL-6 and IL-10 increased gradually until 6
      hr and decreased thereafter. Using this canine endotoxemia model, we were able to
      determine the kinetics of pathophysiologic and immunologic parameters over a
      period of 24 hr. This study will enhance our understanding of their mechanisms
      underlying canine sepsis.

PMID- 22146338
TI  - Lectin histochemistry for sugars on the mucosal surface of the uterus in pregnant
      mice.
AB  - Expression patterns of sugars on the mucosal surface of the uterus in pregnant
      mice were investigated by using 21 kinds of lectins. In the uterine mucosa, the
      GlcNAc group tended to express a positive reaction before pregnant day 10, but
      the glucose/mannose group generally expressed a positive reaction after pregnant
      day 10. On the other hand, the fucose group expressed a negative reaction during
      all periods in pregnancy. These findings were almost the same on both the
      mesometrial side and anti-mesometrial side of the uterus. These differences of
      sugar expression probably reflect the functional change of the mucosa during
      pregnancy and the alteration of sugar expression may give a chance for pathogens
      to infect in the uterus with limited periods.

PMID- 22146339
TI  - Photodynamic hyperthermal therapy with indocyanine green (ICG) induces apoptosis
      and cell cycle arrest in B16F10 murine melanoma cells.
AB  - We examined the effects of photodynamic hyperthemal therapy (PHT), which is a
      combination of photodynamic therapy (PDT) and hyperthermia (HT), on the apoptosis
      and cell cycle progression of murine melanoma B16F10 cells. The percentage of
      apoptotic cell was determined by flow cytometry using fluorescein isothiocyanate
      (FITC)-conjugated Annexin V and propidium iodide (PI) double staining. The cell
      cycle analysis was performed by PI staining with flow cytometry. The expression
      of cyclins and heat shock protein 70 (Hsp70) were examined by a Western blotting
      analysis. PHT induces death in B16F10 cells, and PHT-mediated apoptosis occurred
      acutely and persistently in vitro. Our study demonstrated that PHT using
      indocyanine green (ICG) and near infrared (NIR) light source induces apoptosis
      and G0/G1 cell cycle arrest in the B16F10 cells.

PMID- 22146340
TI  - RNA interference-mediated silencing of BACE and APP attenuates the isoflurane
      induced caspase activation.
AB  - BACKGROUND: beta-Amyloid protein (Abeta) has been shown to potentiate the caspase
      3 activation induced by the commonly used inhalation anesthetic isoflurane.
      However, it is unknown whether reduction in Abeta levels can attenuate the
      isoflurane-induced caspase-3 activation. We therefore set out to determine the
      effects of RNA interference-mediated silencing of amyloid precursor protein (APP)
      and beta-site APP-cleaving enzyme (BACE) on the levels of Abeta and the
      isoflurane-induced caspase-3 activation. METHODS: H4 human neuroglioma cells
      stably transfected to express full-length human APP (H4-APP cells) were treated
      with small interference RNAs (siRNAs) targeted at silencing BACE and APP for 48
      hours. The cells were then treated with 2% isoflurane for six hours. The levels
      of BACE, APP, and caspase-3 were determined using Western blot analysis. Sandwich
      Enzyme-linked immunosorbent assay (ELISA) was used to determine the extracellular
      Abeta levels in the conditioned cell culture media. RESULTS: Here we show for the
      first time that treatment with BACE and APP siRNAs can decrease levels of BACE,
      full-length APP, and APP c-terminal fragments. Moreover, the treatment attenuates
      the Abeta levels and the isoflurane-induced caspase-3 activation. These results
      further suggest a potential role of Abeta in the isoflurane-induced caspase-3
      activation such that the reduction in Abeta levels attenuates the isoflurane
      induced caspase-3 activation. CONCLUSION: These findings will lead to more
      studies which aim at illustrating the underlying mechanism by which isoflurane
      and other anesthetics may affect Alzheimer's disease neuropathogenesis.

PMID- 22146341
TI  - Construction of an oncolytic herpes simplex virus that precisely targets
      hepatocellular carcinoma cells.
AB  - Selective replication in tumor cells is a highly desirable feature for oncolytic
      viruses. Recent studies have shown that microRNAs (miRNAs) play important roles
      in controlling gene expression, and that certain tissue-specific miRNAs are
      frequently downregulated in malignant cells. miR-122 is a liver-specific
      microRNA. It is abundantly expressed in normal hepatocytes but is absent in many
      hepatocellular carcinoma (HCC) cells. We hypothesized that expression of an
      essential viral gene by a liver-specific promoter would initially restrict virus
      replication to cells of hepatic origin and that adding miR-122 complementary
      sequences to the viral gene would make the transcripts degradable by miR-122 in
      normal hepatocytes, thus further confining its replication to HCC. We have
      constructed such an oncolytic herpes simplex virus by linking the essential viral
      glycoprotein H gene with the liver-specific apolipoprotein E (apoE)-AAT promoter
      and by adding the miR-122a complimentary sequence to the 3' untranslated region
      (3'UTR). To further increase the safety of this virus, complementary sequences
      from miR-124a and let-7 were also engineered into the same 3'UTR. Designated
      liver-cancer specific oncolytic virus (LCSOV), it was highly selective in killing
      HCC cells and in shrinking HCC xenografts. We conclude that LCSOV is a highly
      specific oncolytic virus that can precisely target HCC.

PMID- 22146342
TI  - Long-term restoration of cardiac dystrophin expression in golden retriever
      muscular dystrophy following rAAV6-mediated exon skipping.
AB  - Although restoration of dystrophin expression via exon skipping in both cardiac
      and skeletal muscle has been successfully demonstrated in the mdx mouse,
      restoration of cardiac dystrophin expression in large animal models of Duchenne
      muscular dystrophy (DMD) has proven to be a challenge. In large animals,
      investigators have focused on using intravenous injection of antisense
      oligonucleotides (AO) to mediate exon skipping. In this study, we sought to
      optimize restoration of cardiac dystrophin expression in the golden retriever
      muscular dystrophy (GRMD) model using percutaneous transendocardial delivery of
      recombinant AAV6 (rAAV6) to deliver a modified U7 small nuclear RNA (snRNA)
      carrying antisense sequence to target the exon splicing enhancers of exons 6 and
      8 and correct the disrupted reading frame. We demonstrate restoration of cardiac
      dystrophin expression at 13 months confirmed by reverse transcription-PCR (RT
      PCR) and immunoblot as well as membrane localization by immunohistochemistry.
      This was accompanied by improved cardiac function as assessed by cardiac magnetic
      resonance imaging (MRI). Percutaneous transendocardial delivery of rAAV6
      expressing a modified U7 exon skipping construct is a safe, effective method for
      restoration of dystrophin expression and improvement of cardiac function in the
      GRMD canine and may be easily translatable to human DMD patients.

PMID- 22146343
TI  - Efficient and accurate homologous recombination in hESCs and hiPSCs using helper
      dependent adenoviral vectors.
AB  - Low efficiencies of gene targeting via homologous recombination (HR) have limited
      basic research and applications using human embryonic stem cells (hESCs) and
      human induced pluripotent stem cells (hiPSCs). Here, we show highly and equally
      efficient gene knockout and knock-in at both transcriptionally active (HPRT1,
      KU80, LIG1, LIG3) and inactive (HB9) loci in these cells using high-capacity
      helper-dependent adenoviral vectors (HDAdVs). Without the necessity of
      introducing artificial DNA double-strand breaks, 7-81% of drug-resistant colonies
      were gene-targeted by accurate HR, which were not accompanied with additional
      ectopic integrations. Even at the motor neuron-specific HB9 locus, the enhanced
      green fluorescent protein (EGFP) gene was accurately knocked in in 23-57% of drug
      resistant colonies. In these clones, induced differentiation into the HB9
      positive motor neuron correlated with EGFP expression. Furthermore, HDAdV
      infection had no detectable adverse effects on the undifferentiated state and
      pluripotency of hESCs and hiPSCs. These results suggest that HDAdV is one of the
      best methods for efficient and accurate gene targeting in hESCs and hiPSCs and
      might be especially useful for therapeutic applications.

PMID- 22146344
TI  - Mesenchymal stromal cells protect cancer cells from ROS-induced apoptosis and
      enhance the Warburg effect by secreting STC1.
AB  - Previous studies have demonstrated that mesenchymal stromal cells (MSCs) enhance
      cell survival through upregulation and secretion of stanniocalcin-1 (STC1). This
      study shows that MSC-derived STC1 promotes survival of lung cancer cells by
      uncoupling oxidative phosphorylation, reducing intracellular reactive oxygen
      species (ROS), and shifting metabolism towards a more glycolytic metabolic
      profile. MSC-derived STC1 upregulated uncoupling protein 2 (UCP2) in injured A549
      cells in an STC1-dependent manner. Knockdown of UCP2 reduced the ability of MSCs
      and recombinant STC1 (rSTC1) to reduce cell death in the A549 population. rSTC1
      treated A549 cells displayed decreased levels of ROS, mitochondrial membrane
      potential (MMP), and increased lactate production, all of which were dependent on
      the upregulation of UCP2. Our data suggest that MSCs can promote cell survival by
      regulating mitochondrial respiration via STC1.

PMID- 22146345
TI  - Threshold dynamics for periodically forced ecological systems: the control of
      population invasion and exclusion.
AB  - Ecosystems are under increasing threat as a result of anthropogenic activity,
      through pollution, unregulated harvesting, habitat destruction and the
      inadvertent spread of pathogens and vertebrate and non-vertebrate species through
      global transportation links. Many of the necessary interventions to restore or
      restructure natural ecosystems require the exclusion of a population from the
      ecosystem or the inclusion of a population if robust biodiversity is the
      objective. The problem of how best to bring this about is not easy to solve in
      highly nonlinear systems, especially if the system is exposed to significant time
      varying external forces. We wish here to build on the understanding gained from
      previous work by developing an algebraic methodology that yields explicit
      formulae to analyse the effect of moderate multi-component forcing on the
      invasion/exclusion process. This can be of assistance to management in designing
      suitable intervention strategies if one or more of the forcing components is
      under management control. We apply this methodology to look at three important
      issues, involving the relationships between resonance and control, between
      vaccination policy and the stage structure of a disease and between apparent
      competition and coexistence.

PMID- 22146346
TI  - Diagnostic value of a repeat video-EEG study.

PMID- 22146347
TI  - Influence of age and the severity of median nerve compression on forearm median
      motor conduction velocity in carpal tunnel syndrome.
AB  - Forearm median motor conduction velocity (FMCV) is reduced in carpal tunnel
      syndrome (CTS). The aim of this study was to investigate the association of FMCV
      with age and severity of median nerve compression. Forearm median motor
      conduction velocity and median nerve motor distal latencies were measured in 312
      CTS hands. Forearm median motor conduction velocity correlated negatively with
      age. This correlation persisted in the subgroups of hands with severe and less
      severe CTS. Forearm median motor conduction velocity correlated negatively with
      the degree of compression (as measured by median nerve motor distal latencies).
      This correlation persisted in subgroup of hands with severe CTS but not in less
      severe ones. Multiple regression analysis comparing the influence of age and
      median nerve motor distal latencies on FMCV showed higher standardized
      coefficients (beta) value for age than for median nerve motor distal latencies,
      suggesting a greater influence for age. The beta value for age is higher in
      severe group than in less severe group, suggesting that age has higher influence
      on FMCV in severe group. The degree of compression influences FMCV in hands with
      severe CTS but not in hands with less severe CTS. This difference in severe and
      less severe CTS may be because of the differences in the underlying
      pathophysiological processes in the 2 entities.

PMID- 22146348
TI  - Extraoperative electrical cortical stimulation:  characteristics of motor
      responses and correlation with precentral gyrus.
AB  - PURPOSE: To characterize properties and stimulation thresholds of extraoperative
      cortical stimulation with respect to the anatomic area stimulated. METHODS:
      Analysis of 1,496 bipolar extraoperative cortical stimulations with respect to
      stimulation threshold, anatomic area stimulated, afterdischarges (ADs), and
      latencies to observe a clinical sign on video analysis. RESULTS: Cortical
      stimulation mapping stimulus thresholds to induce clinical motor responses are
      lower when compared with stimulus thresholds to induce nonmotor responses (P <
      0.01). Motor thresholds vary depending on the anatomic area stimulated with the
      precentral gyrus, showing lower stimulation thresholds when compared with cortex
      outside the precentral gyrus (P < 0.001). Afterdischarges are more likely to
      occur with motor stimulations outside the precentral gyrus (chi = 1; n = 123; P <
      0.05), and those stimulations show longer latencies to observe an arm motor
      response on video analysis when compared with precentral gyrus stimulations (P <
      0.05). Within the precentral gyrus, stimulation of the hand knob was achieved
      with lower stimulation intensities compared with stimulation outside the hand
      knob (P < 0.001). CONCLUSION: Clinical response thresholds, afterdischarge
      occurrence, and latencies to observe clinical signs during extraoperative
      cortical stimulation vary depending on the cortex stimulated. Findings provide
      information about motor cortex organization and might aid interpreting results
      from extraoperative cortical stimulation in a clinical setting.

PMID- 22146349
TI  - Can event-related potential predict the progression of mild cognitive impairment?
AB  - This study was designed to evaluate the predictive value of event-related
      potential (ERP; N2 and P3b) in patients with mild cognitive impairment (MCI).
      Seventy-one patients with MCI were selected and compared with 31 healthy control
      subjects. They benefited from an initial assessment that included a
      neuropsychological evaluation and ERP. We followed them up for 1 year, and during
      their last visit, they benefited again from ERP and neuropsychological tests. At
      the end of the study, 2 subgroups of patients with MCI were differentiated
      according to their clinical evolution from baseline to follow-up: 41 MCI
      progressors (MCI-P) and 30 MCI nonprogressors (MCI-non P). The MCI-P patients had
      a significant decline in their executive functions compared with the MCI-non-P
      group at baseline and follow-up especially on trail making test B (TMT B) and
      verbal fluency (P < 0.0001). At baseline, MCI-P had increased P3b latencies and
      low P3b amplitudes compared with MCI-non P. The MCI-P showed an inversion of the
      P3b rostrocaudal gradient with a significant decrease in the amplitude of P3b in
      the parietal area compared with the MCI-non P. At follow-up, 17 MCI-P patients
      had converted to Alzheimer's disease (AD). There was a significant rate of
      decline of the amplitude of N2 and P3b in the frontal area among the groups.
      Furthermore, the MCI-P had a higher decrease in the rostrocaudal gradient of P3b
      and prolonged N2 and P3b latencies than the MCI-non P did. The sensitivity and
      specificity were approximately 80% and 70%, using P3b amplitude to discriminate
      the MCI-P from the MCI-non P. Our study underlines the interest of using N2 and
      P3b as neurophysiological markers for measuring MCI decline progression.

PMID- 22146350
TI  - Electroencephalographic findings in acute subdural hematoma.
AB  - The aim was to determine the electroencephalographic (or electroencephalogram
      [EEG]) findings predictive of functional outcome in a subset of patients with
      acute subdural hematoma (SDH) with epileptiform activity on their EEG. Twenty
      four patients who underwent evacuation for acute or acute-on-chronic SDH and with
      epileptiform activity on EEG were identified retrospectively. Their EEGs were
      reviewed and the findings categorized along with clinical information, the
      preoperative computed tomography (CT) scan, and functional outcome. Twenty-one
      patients (87%) had epileptiform discharges on EEG; 13 of them (62%) had midline
      epileptiform discharges and 9 of them (43%) had periodic lateralized epileptiform
      discharges (PLEDs). Both types of epileptiform discharges were significantly
      associated with the degree of midline shift on neuroimaging (P = 0.01, P = 0.04,
      respectively). Poor early outcomes were associated with the presence of bilateral
      (P = 0.03), midline (P = 0.04), and bilateral independent multifocal discharges
      (P = 0.09) on EEG. The EEG findings in this group of patients were complex.
      Epileptiform discharges were common, and specific types were associated with
      midline shift on neuroimaging and poor functional outcome at hospital discharge.
      Improvement in follow-up EEG examinations over time was predictive of good long
      term functional outcome.

PMID- 22146351
TI  - Neurophysiologic intraoperative monitoring of the oculomotor, trochlear, and
      abducens nerves.

PMID- 22146353
TI  - Cranial nerve monitoring.

PMID- 22146352
TI  - Neurophysiologic intraoperative monitoring of the vestibulocochlear nerve.
AB  - Neurosurgical procedures involving the skull base and structures within can pose
      a significant risk of damage to the brain stem and cranial nerves. This can have
      life-threatening consequences and/or result in devastating neurologic deficits.
      Over the past decade, intraoperative neurophysiology has significantly evolved
      and currently offers a great tool for live monitoring of the integrity of nervous
      structures. Thus, dysfunction can be identified early and prompt modification of
      the surgical management or operating conditions, leads to avoidance of permanent
      structural damage.Along these lines, the vestibulocochlear nerve (CN VIII) and,
      to a greater extent, the auditory pathways as they pass through the brain stem
      are especially at risk during cerebelopontine angle (CPA), posterior/middle
      fossa, or brain stem surgery. CN VIII can be damaged by several mechanisms, from
      vascular compromise to mechanical injury by stretch, compression, dissection, and
      heat injury. Additionally, cochlea itself can be significantly damaged during
      temporal bone drilling, by noise, mechanical destruction, or infarction, and
      because of rupture, occlusion, or vasospasm of the internal auditory artery.CN
      VIII monitoring can be successfully achieved by live recording of the function of
      one of its parts, the cochlear or auditory nerve (AN), using the brain stem
      auditory evoked potentials (BAEPs), electrocochleography (ECochG), and compound
      nerve action potentials (CNAPs) of the cochlear nerve.This is a review of these
      techniques, their principle, applications, methodology, interpretation of the
      evoked responses, and their change from baseline, within the context of surgical
      and anesthesia environments, and finally the appropriate management of these
      changes.

PMID- 22146354
TI  - Visual-evoked potentials for intraoperative neurophysiology monitoring:  another
      flash in the pan?

PMID- 22146355
TI  - A new multicenter survey of neurologic deficits after spinal deformity surgery: 
      are new models of intraoperative neurophysiologic monitoring less accurate?

PMID- 22146356
TI  - Direct lateral transpsoas approach to interbody fusion--may be risky after all.

PMID- 22146357
TI  - Are there false-negative and false-positive motor-evoked potentials?

PMID- 22146358
TI  - Neurophysiologic intraoperative monitoring of olfactory and optic nerves.
AB  - Olfaction and vision are two sensory functions that can be lost during surgery.
      Intraoperative neurophysiologic monitoring can be used to monitor the integrity
      of the olfactory and the visual pathways during surgery. No objective methods
      have been established to test olfactory evoked potentials (OEPs) in the operating
      room. It is a challenge to obtain reliable visual-evoked potentials (VEPs) in the
      operating room. However, it would be very valuable to reliably monitor these
      pathways during surgery to predict and prevent iatrogenic neurologic injury. The
      aim of the review is to describe the techniques used to obtain OEPs and VEPs, the
      surgical procedures in which they can be used to prevent deficits, and the
      limitations of the current techniques and future directions for research.

PMID- 22146359
TI  - The American Clinical Neurophysiology Society's Guideline on Continuous
      Electroencephalography Monitoring in Neonates.

PMID- 22146360
TI  - Neurophysiologic intraoperative monitoring of the glossopharyngeal and vagus
      nerves.
AB  - Neurophysiologic intraoperative monitoring (NIOM) of the glossopharyngeal and
      vagus nerves (CN IX and X) is often used during surgeries involving the lower
      brain stem. Although both of these nerves contain sensory, autonomic, and motor
      fibers, it is the motor fibers that are most amenable to NIOM. CN IX supplies the
      stylopharyngeus muscle, and CN X supplies striated muscles in the soft palate,
      pharynx, and larynx. Monitoring of these CN can be performed by monitoring free
      running and stimulated electromyography (EMG) from the stylopharyngeus muscle (CN
      IX) and the vocal cords (CN X). Various surface and needle electrodes can be used
      to monitor these muscle groups. When CN IX is monitored, CN X should also be
      monitored, as it is often needed to differentiate when CN IX is selectively
      activated. Data are accumulating noting the use of monitoring these CN in tumor
      surgeries involving the lower brain stem.

PMID- 22146361
TI  - Neurophysiologic monitoring of the spinal accessory nerve, hypoglossal nerve, and
      the spinomedullary region.
AB  - This review of hypoglossal nerve, spinal accessory nerve, and spinomedullary
      region intraoperative monitoring details pertinent central and extramedullary
      anatomy, an updated understanding of proper free-run EMG recording methods and
      recent developments in stimulation technique and instrumentation. Mapping and
      monitoring the floor of the fourth ventricle, especially the vagal/hypoglossal
      trigone region, are emphasized. Although cranial nerve transcranial electrical
      motor evoked potential recordings can afford appreciation of
      corticobulbar/corticospinal tract function and secure a more dependable measure
      of proximate extramedullary somatoefferents, the sometimes difficult
      implementation and the, as yet, unresolved alert criteria of these recordings
      demand critical appraisal. Nearby and intimately associated cardiochronotropic
      and barocontrol neural networks are described; their better understanding is
      recommended as an important adjunct to "routine" neural monitoring. Finally, an
      Illustrative case is presented to highlight the many strengths and weaknesses of
      "state of the art" lower cranial nerve/spinomedullary region monitoring.

PMID- 22146362
TI  - Neurophysiologic intraoperative monitoring of trigeminal and facial nerves.
AB  - The trigeminal and facial nerves are placed at risk in a number of surgical
      procedures. The use of electromyography, nerve conduction studies, somatosensory
      evoked potentials, motor evoked potentials, and other techniques are described.
      Application to specific surgical types and the associated evidence for impact on
      surgical outcomes are discussed.

PMID- 22146363
TI  - Interference in spin tunnelling of small magnetic particles.
AB  - A previously studied (Enz and Schilling 1986  J. Phys. C: Solid State Phys.  19
      1765) magnetocrystalline anisotropic Hamiltonian with a magnetic field applied
      along the medium axis is reconsidered, with emphasis on the topological phase
      effect. A quantum inteference effect is revealed.

PMID- 22146365
TI  - Molecular hydrogen protects chondrocytes from oxidative stress and indirectly
      alters gene expressions through reducing peroxynitrite derived from nitric oxide.
AB  - BACKGROUND: Molecular hydrogen (H2) functions as an extensive protector against
      oxidative stress, inflammation and allergic reaction in various biological models
      and clinical tests; however, its essential mechanisms remain unknown. H2 directly
      reacts with the strong reactive nitrogen species peroxynitrite (ONOO-) as well as
      hydroxyl radicals (*OH), but not with nitric oxide radical (NO*). We hypothesized
      that one of the H2 functions is caused by reducing cellular ONOO-, which is
      generated by the rapid reaction of NO* with superoxides (*O2-). To verify this
      hypothesis, we examined whether H2 could restore cytotoxicity and transcriptional
      alterations induced by ONOO- derived from NO* in chondrocytes. METHODS: We
      treated cultured chondrocytes from porcine hindlimb cartilage or from rat
      meniscus fibrecartilage with a donor of NO*, S-nitroso-N-acetylpenicillamine
      (SNAP) in the presence or absence of H2. Chondrocyte viability was determined
      using a LIVE/DEAD Viability/Cytotoxicity Kit. Gene expressions of the matrix
      proteins of cartilage and the matrix metalloproteinases were analyzed by reverse
      transcriptase-coupled real-time PCR method. RESULTS: SNAP treatment increased the
      levels of nitrated proteins. H2 decreased the levels of the nitrated proteins,
      and suppressed chondrocyte death. It is known that the matrix proteins of
      cartilage (including aggrecan and type II collagen) and matrix metalloproteinases
      (such as MMP3 and MMP13) are down- and up-regulated by ONOO-, respectively. H2
      restoratively increased the gene expressions of aggrecan and type II collagen in
      the presence of H2. Conversely, the gene expressions of MMP3 and MMP13 were
      restoratively down-regulated with H2. Thus, H2 acted to restore transcriptional
      alterations induced by ONOO-. CONCLUSIONS: These results imply that one of the
      functions of H2 exhibits cytoprotective effects and transcriptional alterations
      through reducing ONOO-. Moreover, novel pharmacological strategies aimed at
      selective removal of ONOO- may represent a powerful method for preventive and
      therapeutic use of H2 for joint diseases.

PMID- 22146366
TI  - [Autoantibodies against tumor-related antigens: new tools for early detection of
      lung cancer].
AB  - Because of its development marked by a long preclinical phase and the
      difficulties to screen patients, lung cancer is usually diagnosed at an advanced
      stage of disease, even in high-risk populations. The advent of new molecular
      tools, including proteomics, has promoted the study of the humoral response to
      cancer and has allowed the demonstration of the appearance of a large number of
      autoantibodies against tumor antigens in the serum of patients. In this article,
      we describe the different molecular approaches used to identify autoantibodies
      and immunogenic proteins and we present the different clinical studies applied to
      early detection of lung cancer. Early trials demonstrated the development of a
      humoral response several months before the first radiographic or clinical signs.
      Further studies are under evaluation and are intended to identify early forms of
      cancer in populations with high cancer risk. Many efforts are made in the
      implementation of robust and reproducible tests that could help to the emergence
      in the future of such biological tools in clinical practice.

PMID- 22146367
TI  - Commentary to 'non-invasive vesicoureteral reflux detection: heating risk studies
      for a new device'.

PMID- 22146368
TI  - Deep vein thrombosis in a young marathon athlete.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: A 21-year-old athletic male
      college student presented to a direct-access physical therapy clinic with
      complaints of left calf pain 4 days in duration. After initial examination, a
      working diagnosis of calf strain was formulated. Three days following initial
      examination, the patient reported 80% improvement in symptoms and was performing
      activities of daily living pain free. Four weeks later, the patient returned with
      complaints of reoccurring calf pain. The patient's signs, symptoms, and history
      at subsequent follow-up no longer presented a consistent clinical picture of calf
      strain; therefore, a D-dimer assay was ordered to rule out a deep vein thrombosis
      (DVT). DIAGNOSIS: The D-dimer was elevated so the patient was admitted to the
      hospital and started on low-molecular-weight heparin. A compression ultrasound
      revealed an extensive left superficial femoral and popliteal DVT in this
      otherwise healthy athlete. DISCUSSION: Lower extremity DVT is a serious and
      potentially fatal disorder. Physical therapists need to be diagnostically
      vigilant for vascular pathology in all patients with extremity pain and swelling.
      Employing the best current evidenced-based screening tools to rule out vascular
      pathology, such as deep and superficial vein pathology, should be the goal of
      every clinician. The Wells score is one such screening tool that has proven to be
      beneficial in this area. This case report presents a dilemma in diagnosis and
      illustrates the importance of revisiting differential diagnoses with each patient
      encounter. Clinicians must consider the possibility of a DVT with every patient
      seen with posterior leg pain. LEVEL OF EVIDENCE: Diagnosis, level 4.
      doi:10.2519/jospt.2011.3823.

PMID- 22146369
TI  - Size-dependent electrocatalytic activity of gold nanoparticles on HOPG and highly
      boron-doped diamond surfaces.
AB  - Gold nanoparticles were prepared by electrochemical deposition on highly oriented
      pyrolytic graphite (HOPG) and boron-doped, epitaxial 100-oriented diamond layers.
      Using a potentiostatic double pulse technique, the average particle size was
      varied in the range from 5 nm to 30 nm in the case of HOPG as a support and
      between < 1 nm and 15 nm on diamond surfaces, while keeping the particle density
      constant. The distribution of particle sizes was very narrow, with standard
      deviations of around 20% on HOPG and around 30% on diamond. The electrocatalytic
      activity towards hydrogen evolution and oxygen reduction of these carbon
      supported gold nanoparticles in dependence of the particle sizes was investigated
      using cyclic voltammetry. For oxygen reduction the current density normalized to
      the gold surface (specific current density) increased for decreasing particle
      size. In contrast, the specific current density of hydrogen evolution showed no
      dependence on particle size. For both reactions, no effect of the different
      carbon supports on electrocatalytic activity was observed.

PMID- 22146370
TI  - Genetic diversity and identification of Chinese-grown pecan using ISSR and SSR
      markers.
AB  - Pecan is an important horticultural nut crop originally from North America and
      now widely cultivated in China for its high ecological, ornamental and economic
      value. Currently, there are over one hundred cultivars grown in China, including
      introduced American cultivars and Chinese seedling breeding cultivars. Molecular
      markers were used to assess the genetic diversity of these cultivars and to
      identify the pedigrees of fine pecan plants with good characteristics and no
      cultivar-related data. A total of 77 samples grown in China were studied,
      including 14 introduced cultivars, 12 domestic seedling breeding cultivars, and
      49 fine pecan plants with no cultivar data, together with Carya cathayensis and
      Juglans nigra. A total of 77 ISSR and 19 SSR primers were prescreened; 10 ISSR
      and eight SSR primers were selected, yielding a total of 94 amplified bands (100%
      polymorphic) in the range of 140-1,950 bp for the ISSR and 70 amplified bands
      (100% polymorphic) in the range of 50-350 bp for SSR markers. Genetic diversity
      analyses indicated Chinese-grown pecan cultivars and fine plants had significant
      diversity at the DNA level. The dengrograms constructed with ISSR, SSR or
      combined data were very similar, but showed very weak grouping association with
      morphological characters. However, the progeny were always grouped with the
      parents. The great diversity found among the Chinese cultivars and the
      interesting germplasm of the fine pecan plants analyzed in this study are very
      useful for increasing the diversity of the pecan gene pool. All 77 accessions in
      this study could be separated based on the ISSR and SSR fingerprints produced by
      one or more primers. The results of our study also showed that ISSR and SSR
      techniques were both suitable for genetic diversity analyses and the
      identification of pecan resources.

PMID- 22146372
TI  - Free-radical scavenging properties and reducing power of grape cane extracts from
      11 selected grape cultivars widely grown in China.
AB  - Total phenolic contents (TPC), total flavonoid contents (TFC), related
      antioxidative and antiradical capabilities of grape cane extracts from 11
      varieties (five V. vinifera cultivars and six Chinese wild grapes) widely grown
      in China were evaluated. Antioxidant properties were determined as DPPH and ABTS
      radical-scavenging abilities, superoxide anion and hydroxyl radical and hydrogen
      peroxide scavenging assays, as well as reducing power. Phenolic profiles of the
      extracts were characterized by using high-performance liquid chromatography
      (HPLC) techniques. All extracts exhibited strong antioxidant and effective free
      radical inhibition activities (EC(50) values), which generally correlated
      negatively with TPC (r = -0.804 to -0.918) and TFC (r = -0.749 to -0.888). In
      comparison with gallic acid, Trolox and tert-butylhydroquinone (positive
      controls), most grape cane extracts showed more efficient scavenging effects
      toward different reactive oxygen species. HPLC analysis revealed the presence of
      (+)-catechin, (-)-epicatechin, and trans-resveratrol as major phenolic components
      in the extracts. These results suggest that grape cane extracts may serve as a
      potential source of natural antioxidant for food and pharmaceutical application.

PMID- 22146371
TI  - Snailase preparation of ginsenoside M1 from protopanaxadiol-type ginsenoside and
      their protective effects against CCl4-induced chronic hepatotoxicity in mice.
AB  - To investigate the protective effects of protopanaxadiol-type ginsenoside (PDG)
      and its metabolite ginsenoside M1 (G-M1) on carbon tetrachloride (CCl(4))-induced
      chronic liver injury in ICR mice, we carried out conversion of protopanaxadiol
      type ginsenosides to ginsenoside M1 using snailase. The optimum time for the
      conversion was 24 h at a constant pH of 4.5 and an optimum temperature of 50 
      degrees C. The transformation products were identified by high-performance liquid
      chromatography and electrospray ion-mass spectrometry. Subsequently, most of PDG
      was decomposed and converted into G-M1 by 24 h post-reaction. During the study on
      hepatoprotective in a mice model of chronic liver injury, PDG or G-M1 supplement
      significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum
      levels of select hepatic enzyme markers (alanine aminotransferase, ALT, and
      aspartate aminotransferase, AST) and malondialdehyde and increased the activity
      of superoxide dismutase in liver. Histopathology of the liver tissues showed that
      PDG and G-M1 attenuated the hepatocellular necrosis and led to reduction of
      inflammatory cell infiltration. Therefore, the results of this study show that
      PDG and G-M1 can be proposed to protect the liver against CCl(4)-induced
      oxidative injury in mice, and the hepatoprotective effect might be attributed to
      amelioration of oxidative stress.

PMID- 22146373
TI  - The dose-effect of icariin on the proliferation and osteogenic differentiation of
      human bone mesenchymal stem cells.
AB  - Icariin had been reported as a potential agent for osteogenesis, but the dose
      effect relationship needed further research to realize the clinical application
      of icariin. We isolated and purified human bone mesenchymal stem cells (hBMSCs)
      and stimulated them with different concentrations of icariin. The cytotoxicity of
      icariin was evaluated by the methylthiazolytetrazolium (MTT) assay method. The
      proliferation and osteogenic differentiation of such hBMSCs were investigated for
      different concentrations of icariin. We found that icariin had a dose-dependent
      effect on the proliferation and osteogenic differentiation of hBMSCs in a
      suitable concentration range from 10(-9) M to 10(-6) M, but at concentrations
      above 10(-5) M, the cytotoxicity limited its use. The extremely low cost of
      icariin and its high abundance make it appealing for bone regeneration.

PMID- 22146374
TI  - Hepatoprotective potential of Clitoria ternatea leaf extract against paracetamol
      induced damage in mice.
AB  - BACKGROUND AND AIM: Clitoria ternatea, a medicinal herb native to tropical
      equatorial Asia, is commonly used in folk medicine to treat various diseases. The
      aim of the present study is to evaluate the hepatoprotective and antioxidant
      activity of C. ternatea against experimentally induced liver injury. METHODS: The
      antioxidant property of methanolic extract (ME) of C. ternatea leaf was
      investigated by employing an established in vitro antioxidant assay. The
      hepatoprotective effect against paracetamol-induced liver toxicity in mice of ME
      of C. ternatea leaf was also studied. Activity was measured by monitoring the
      levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
      billirubin along with histopathological analysis. RESULTS: The amount of total
      phenolics and flavonoids were estimated to be 358.99 +/- 6.21 mg/g gallic acid
      equivalent and 123.75 +/- 2.84 mg/g catechin equivalent, respectively. The
      antioxidant activity of C. ternatea leaf extract was 67.85% at a concentration of
      1 mg/mL and was also concentration dependant, with an IC(50) value of 420.00
      ug/mL. The results of the paracetamol-induced liver toxicity experiments showed
      that mice treated with the ME of C. ternatea leaf (200 mg/kg) showed a
      significant decrease in ALT, AST, and bilirubin levels, which were all elevated
      in the paracetamol group (p < 0.01). C. ternatea leaf extract therapy also
      protective effects against histopathological alterations. Histological studies
      supported the biochemical findings and a maximum improvement in the
      histoarchitecture was seen. CONCLUSIONS: The current study confirmed the
      hepatoprotective effect of C. ternatea leaf extract against the model
      hepatotoxicant paracetamol. The hepatoprotective action is likely related to its
      potent antioxidative activity.

PMID- 22146375
TI  - BDNF promotes EGF-induced proliferation and migration of human fetal neural
      stem/progenitor cells via the PI3K/Akt pathway.
AB  - Neurogenesis is a complex process, which contributes to the ability of the adult
      brain to function normally and adapt to diseases. Epidermal growth factor (EGF)
      is known to play an important role in neurogenesis; however, the underlying
      mechanism is still unclear. Here, we hypothesized that brain-derived neurotrophic
      factor (BDNF) can enhance the effect of EGF on neurogenesis. Using in vitro cell
      culture of aborted human fetal brain tissues, we investigated proliferation and
      migration of neural stem/progenitor cells (NSPCs) after treatment with EGF and
      different concentrations of BDNF. EGF stimulated proliferation and migration of
      NSPCs, and this effect was significantly enhanced by co-incubation with BDNF. In
      the NSPCs treated with 50 ng/mL BDNF, BrdU incorporation was significantly
      increased (from 7.91% to 17.07%), as compared with that in the control. Moreover,
      the number of migrating cells was at least 2-fold higher than that in the
      control. Furthermore, phosphorylation of Akt-1 was increased by BDNF treatment,
      as well. By contrast, the enhancing effect of BDNF on EGF-induced proliferation
      and migration of NSPCs were abolished by an inhibitor of PI3K, LY294002. These
      findings suggest that BDNF promotes EGF-induced proliferation and migration of
      NSPC through the PI3K/Akt pathway, providing significant insights into not only
      the mechanism underlying EGF-induced neurogenesis but also potential neuronal
      replacement strategies to treat brain damage.

PMID- 22146376
TI  - Sharing breathlessness: investigating respiratory change during observation of
      breath-holding in another.
AB  - Studies of empathy show that seeing another person in pain, fear or disgust
      elicits the same brain activations associated with pain, fear or disgust in
      oneself. Our interest is to know whether respiratory change can be observed in
      empathy, that is, whether respiration can be altered when observing emotions in
      others. A discomfort associated with respiration can be breathlessness. We
      investigated respiratory pattern and metabolic response during observation of a
      breath-holding subject. We found that breathlessness occurred in participants who
      observed breath-holding in another person. It is interesting to note that
      observers felt more breathlessness after breath-holding ended with an increase in
      respiratory rate consistent with the breath-holder's respiratory pattern. In
      addition, observers with high trait anxiety felt more breathlessness accompanied
      with an increase in respiratory rate. An increase in respiratory rate may be
      involved in the perception of breathlessness, in addition to the effect of
      observing breath-holding, indicating shared negative emotion.

PMID- 22146377
TI  - The values of defibrillation testing at implantable cardioverter defibrillator
      implantation:  'and then there were none'.
AB  - PURPOSE OF REVIEW: Since its advent, implantable cardioverter defibrillator (ICD)
      intra-operative defibrillation testing (DFT) has been a standard practice to
      confirm its optimal configuration. However, due to advances in device and lead
      technology, which now facilitate successful device implantation, and due to
      growing number of ICD primary prevention patients, the need for DFT has recently
      been questioned. The purpose of this review is to summarize the pro and contra
      DFT arguments, according to benefits, risk and clinical relevance, trying to
      identify the candidates for whom DFT is really indicated. RECENT FINDINGS: There
      is an ongoing debate on the need for DFT at ICD implant due to significant DFT
      related complications; recently, many electrophysiologists have chosen not to
      perform DFT in many cases. Recent literature findings document large differences
      of practice between different centres and countries. In particular, there has
      been major debate and concern over performing DFT in patients with heart failure,
      indicated for CRT-D implants (cardiac resynchronization therapy with
      defibrillator). SUMMARY: Due to the potential for serious complications during
      DFT and expanding primary prevention ICD candidates, we agree with the growing
      tendency not to routinely perform DFT at implant, as the risks may overweigh the
      benefits.

PMID- 22146378
TI  - The use of anticoagulation during the periprocedure period of atrial fibrillation
      ablation.
AB  - PURPOSE OF REVIEW: Ablation is a treatment option for selected patients with
      atrial fibrillation that is being used more frequently, increasing the importance
      of awareness of both its risks and benefits. This review discusses the
      thromboembolic and bleeding risks during ablation, strategies to minimize these
      risks and use of long-term oral anticoagulation post ablation. RECENT FINDINGS:
      Thromboembolic and bleeding risks imparted by atrial fibrillation ablation can be
      minimized by echocardiography, optimal intraprocedural anticoagulation, and use
      of irrigated catheters and access sheaths with constant heparinized saline flow.
      Additionally, a strategic approach to periprocedural anticoagulation that may
      include continuation of warfarin, bridging with low-molecular-weight heparin
      (LMWH), or use of aspirin alone is essential in the balance of thrombotic and
      hemorrhagic risks. Novel anticoagulants (direct thrombin inhibitors or anti-Xa
      inhibitors) may add further options. SUMMARY: The use of atrial fibrillation
      ablation has increased over the past decade. Along with technique and technology
      advances that have improved the success of ablation, strides have been made in
      minimizing thromboembolic and bleeding risks and in the availability of a broader
      choice of anticoagulants. Research is ongoing to identify patients most suitable
      for ablation and to determine the long-term efficacy and safety of this treatment
      option.

PMID- 22146379
TI  - Current world literature.

PMID- 22146381
TI  - Terbuthylazine in hair as a biomarker of exposure.
AB  - Terbuthylazine (TBA) is an herbicide widely used in corn cultivation. Herein we
      evaluate the measurement of hair TBA as biomarkers of exposure. Five Sprague
      Dawley rats were gavaged with TBA for 3 days, and then the back hair was shaved
      and analyzed for TBA. In addition, head hair samples from 10 corn farmers, 9
      rural residents, and 6 urban residents were collected at the end of the
      application season. Hair TBA was detected by liquid chromatography triple
      quadrupole mass spectrometry after solvent extraction. TBA was quantifiable in
      all rat samples with a mean concentration of 0.92 (+/-0.26)ng/mg, which
      corresponds to a 0.12% incorporation rate. TBA was quantifiable in all farmer
      samples (median: 0.67ng/mg), in 75% of rural resident samples (0.01ng/mg) and in
      none of the urban resident samples (<0.01ng/mg), with a statistical difference
      among groups (P<0.01). Our results suggest that TBA is incorporated in hair and
      prompt further investigation on the use of hair TBA as a potential biomarker of
      cumulative exposure.

PMID- 22146382
TI  - Does vitamin E-stabilized ultrahigh-molecular-weight polyethylene address
      concerns of cross-linked polyethylene in total knee arthroplasty?
AB  - Concerns about reduced strength, fatigue resistance, and oxidative stability of
      highly cross-linked and remelted ultrahigh-molecular-weight polyethylene (UHMWPE)
      have limited its clinical acceptance for total knee arthroplasty. We hypothesized
      that a highly cross-linked UHMWPE stabilized with vitamin E would have less
      oxidation and loss of mechanical properties. We compared the oxidation, in vitro
      strength, fatigue-crack propagation resistance, and wear of highly cross-linked
      UHMWPE doped with vitamin E to gamma-inert-sterilized direct compression-molded
      UHMWPE (control). After accelerated aging, the control material showed elevated
      oxidation, loss of small-punch mechanical properties, and loss of fatigue-crack
      propagation resistance. In contrast, the vitamin E-stabilized material had
      minimal changes and exhibited 73% to 86% reduction in wear for both cruciate
      retaining and posterior-stabilized total knee arthroplasty designs. Highly cross
      linked vitamin E-stabilized UHMWPE performed well in vitro.

PMID- 22146383
TI  - Salvage of failed trochanteric fracture fixation using the Revitan curved
      cementless modular hip arthroplasty.
AB  - Failed internal fixation of an intertrochanteric or subtrochanteric fracture
      often leads to persistent pain and diminished function. This study evaluated 16
      patients treated with Revitan curved cementless modular stem (Zimmer GmbH,
      Winterthur, Switzerland). At a mean follow-up period of 60 months, all patients
      demonstrated clinically significant pain relief and return to ambulation after
      salvage total hip arthroplasty. Mean Harris Hip Score improved from 17.8 to 87.7
      points postoperatively. Radiographic follow-up demonstrated stable stem and bony
      ingrowth in 16 patients without evidence of subsidence. Eight patients had slight
      awareness of lateral trochanteric pain with no compromise of activities, and 1
      patient had nonunion of the greater trochanter. Revitan curved cementless modular
      stem represents a useful treatment option in salvage total hip arthroplasty of
      failed pertrochanteric fixation.

PMID- 22146384
TI  - Shortening cemented femoral implants: an in vitro investigation to quantify
      exeter femoral implant rotational stability vs simulated implant length.
AB  - The Exeter stems vary in length from 90 to 150 mm. The shorter stems generally
      have lower offsets. The purpose of this study was to determine if length of stem,
      with fixed offset, affected rotational stability. Mechanical testing was carried
      out on 10 implant-cement constructs with 2 loading profiles, rising from chair
      and stair climbing, at different simulated implant lengths using purpose-built
      apparatus. This paper presents a mechanism for clinically observed rotational
      stability and explains the mechanical characteristics required for rotational
      stability in Exeter femoral stems.

PMID- 22146385
TI  - An electron paramagnetic resonance study of the tetragonally distorted [Formula:
      see text] ion in [Formula: see text] and [Formula: see text].
AB  - Chromium-doped [Formula: see text] and [Formula: see text] have been studied by
      both EPR and ENDOR spectroscopy. [Formula: see text] ions enter the fluorite
      structure in distorted substitution cation sites. In both matrices the distortion
      observed is tetragonal. X- and Q-band EPR measurements at temperatures between 4
      and 300 K allowed us to determine the ion symmetry and the following spin
      Hamiltonian parameters: [Formula: see text], [Formula: see text], [Formula: see
      text], [Formula: see text] and [Formula: see text] for [Formula: see text]; and
      [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see
      text], [Formula: see text] and [Formula: see text] for [Formula: see text]. For
      [Formula: see text], the weak superhyperfine interaction of [Formula: see text]
      with the surrounding [Formula: see text] ions has been studied by both EPR and
      ENDOR techniques for [Formula: see text]. No ENDOR signals were detected for
      [Formula: see text]. The results are tentatively explained in terms of a Jahn -
      Teller effect corresponding to [Formula: see text] coupling strongly stabilized
      by lattice stresses, although other possible origins for the distortion cannot be
      completely ruled out.

PMID- 22146386
TI  - Relevance of T2 signal changes in the assessment of progression of glioblastoma
      according to the Response Assessment in Neurooncology criteria.
AB  - BACKGROUND: According to the Response Assessment in Neurooncology (RANO)
      criteria, significant nonenhancing signal increase in T2-weighted images
      qualifies for progression in high-grade glioma (T2-progress), even if there is no
      change in the contrast-enhancing tumor portion. The purpose of this retrospective
      study was to assess the frequency of isolated T2-progress and its predictive
      value on subsequent T1-progress, as determined by a T2 signal increase of 15% or
      25%, respectively. The frequency of T2-progress was correlated with
      antiangiogenic therapy. PATIENTS AND METHODS: MRI follow-up examinations (n =
      777) of 144 patients with histologically proven glioblastoma were assessed for
      contrast-enhanced T1 and T2-weighted images. Examinations were classified as T1
      progress, T2-progress with 15% or 25% T2-signal increase, stable disease, or
      partial or complete response. RESULTS: Thirty-five examinations revealed
      exclusive T2-progress using the 15% criterion, and only 2 examinations qualified
      for the 25% criterion; 61.8% of the scans presenting T2-progress and 31.5% of the
      scans presenting stable disease revealed T1-progress in the next follow-up
      examination. The chi(2) test showed a highly significant correlation (P < .001)
      between T2-progress, with the 15% criterion and subsequent T1-progress. No
      correlation between antiangiogenic therapy and T2-progress was shown. CONCLUSION:
      Tumor progression, as determined by both contrast-enhanced T1 and T2 sequences is
      more frequently diagnosed than when considering only contrast-enhanced T1
      sequences. Definition of T2-progress by a 15% T2-signal increase criterion is
      superior to a 25% criterion. The missing correlation of T2-progress and
      antiangiogenic therapy supports the hypothesis of T2-progress as part of the
      natural course of the tumor disease.

PMID- 22146387
TI  - Oxygen/ozone as a medical gas mixture. A critical evaluation of the various
      methods clarifies positive and negative aspects.
AB  - Besides oxygen, several other gases such as NO, CO, H2, H2S, Xe and O3 have come
      to age over the past few years. With regards to O3, its mechanisms of action in
      medicine have been clarified during the last two decades so that now a
      comprehensive framework for understanding and recommending ozone therapy in
      various pathologies is available. O3 used within the determined therapeutic
      window is absolutely safe and more effective than golden standard medications in
      numerous pathologies, like vascular diseases. However, ozone therapy is mostly in
      practitioners' hands and some recent developments for increasing cost
      effectiveness and speed of treatment are neither standardized, nor evaluated
      toxicologically. Hence, the aim of this article is to emphasize the need to
      objectively assess the pros and cons of oxygen/ozone as a medical gas mixture in
      the hope that ozone therapy will be accepted by orthodox medicine in the near
      future.

PMID- 22146388
TI  - Reinforcement learning in professional basketball players.
AB  - Reinforcement learning in complex natural environments is a challenging task
      because the agent should generalize from the outcomes of actions taken in one
      state of the world to future actions in different states of the world. The extent
      to which human experts find the proper level of generalization is unclear. Here
      we show, using the sequences of field goal attempts made by professional
      basketball players, that the outcome of even a single field goal attempt has a
      considerable effect on the rate of subsequent 3 point shot attempts, in line with
      standard models of reinforcement learning. However, this change in behaviour is
      associated with negative correlations between the outcomes of successive field
      goal attempts. These results indicate that despite years of experience and high
      motivation, professional players overgeneralize from the outcomes of their most
      recent actions, which leads to decreased performance.

PMID- 22146390
TI  - Graphene chiral liquid crystals and macroscopic assembled fibres.
AB  - Chirality and liquid crystals are both widely expressed in nature and biology.
      Helical assembly of mesophasic molecules and colloids may produce intriguing
      chiral liquid crystals. To date, chiral liquid crystals of 2D colloids have not
      been explored. As a typical 2D colloid, graphene is now receiving unprecedented
      attention. However, making macroscopic graphene fibres is hindered by the poor
      dispersibility of graphene and by the lack of an assembly method. Here we report
      that soluble, chemically oxidized graphene or graphene oxide sheets can form
      chiral liquid crystals in a twist-grain-boundary phase-like model with
      simultaneous lamellar ordering and long-range helical frustrations. Aqueous
      graphene oxide liquid crystals were continuously spun into metres of macroscopic
      graphene oxide fibres; subsequent chemical reduction gave the first macroscopic
      neat graphene fibres with high conductivity and good mechanical performance. The
      flexible, strong graphene fibres were knitted into designed patterns and into
      directionally conductive textiles.

PMID- 22146389
TI  - Observation of an anomalous decoherence effect in a quantum bath at room
      temperature.
AB  - The decoherence of quantum objects is a critical issue in quantum science and
      technology. It is generally believed that stronger noise causes faster
      decoherence. Strikingly, recent theoretical work suggests that under certain
      conditions, the opposite is true for spins in quantum baths. Here we report an
      experimental observation of an anomalous decoherence effect for the electron spin
      1 of a nitrogen-vacancy centre in high-purity diamond at room temperature. We
      demonstrate that, under dynamical decoupling, the double-transition can have
      longer coherence time than the single-transition even though the former couples
      to the nuclear spin bath as twice strongly as the latter does. The excellent
      agreement between the experimental and theoretical results confirms the
      controllability of the weakly coupled nuclear spins in the bath, which is useful
      in quantum information processing and quantum metrology.

PMID- 22146391
TI  - Magnetic resonance force microscopy of paramagnetic electron spins at millikelvin
      temperatures.
AB  - Magnetic resonance force microscopy (MRFM) is a powerful technique to detect a
      small number of spins that relies on force detection by an ultrasoft magnetically
      tipped cantilever and selective magnetic resonance manipulation of the spins.
      MRFM would greatly benefit from ultralow temperature operation, because of lower
      thermomechanical noise and increased thermal spin polarization. Here we
      demonstrate MRFM operation at temperatures as low as 30 mK, thanks to a recently
      developed superconducting quantum interference device (SQUID)-based cantilever
      detection technique, which avoids cantilever overheating. In our experiment, we
      detect dangling bond paramagnetic centres on a silicon surface down to
      millikelvin temperatures. Fluctuations of such defects are supposedly linked to
      1/f magnetic noise and decoherence in SQUIDs, as well as in several
      superconducting and single spin qubits. We find evidence that spin diffusion has
      a key role in the low-temperature spin dynamics.

PMID- 22146392
TI  - The evolution of sensory divergence in the context of limited gene flow in the
      bumblebee bat.
AB  - The sensory drive theory of speciation predicts that populations of the same
      species inhabiting different environments can differ in sensory traits, and that
      this sensory difference can ultimately drive speciation. However, even in the
      best-known examples of sensory ecology driven speciation, it is uncertain whether
      the variation in sensory traits is the cause or the consequence of a reduction in
      levels of gene flow. Here we show strong genetic differentiation, no gene flow
      and large echolocation differences between the allopatric Myanmar and Thai
      populations of the world's smallest mammal, Craseonycteris thonglongyai, and
      suggest that geographic isolation most likely preceded sensory divergence. Within
      the geographically continuous Thai population, we show that geographic distance
      has a primary role in limiting gene flow rather than echolocation divergence. In
      line with sensory-driven speciation models, we suggest that in C. thonglongyai,
      limited gene flow creates the suitable conditions that favour the evolution of
      sensory divergence via local adaptation.

PMID- 22146393
TI  - Band structure engineering in (Bi(1-x)Sb(x))(2)Te(3) ternary topological
      insulators.
AB  - Topological insulators (TIs) are quantum materials with insulating bulk and
      topologically protected metallic surfaces with Dirac-like band structure. The
      most challenging problem faced by current investigations of these materials is to
      establish the existence of significant bulk conduction. Here we show how the band
      structure of topological insulators can be engineered by molecular beam epitaxy
      growth of (Bi(1-x)Sb(x))(2)Te(3) ternary compounds. The topological surface
      states are shown to exist over the entire composition range of (Bi(1
      x)Sb(x))(2)Te(3), indicating the robustness of bulk Z(2) topology. Most
      remarkably, the band engineering leads to ideal TIs with truly insulating bulk
      and tunable surface states across the Dirac point that behaves like one-quarter
      of graphene. This work demonstrates a new route to achieving intrinsic quantum
      transport of the topological surface states and designing conceptually new
      topologically insulating devices based on well-established semiconductor
      technology.

PMID- 22146394
TI  - Gate-tuned normal and superconducting transport at the surface of a topological
      insulator.
AB  - Three-dimensional topological insulators are characterized by the presence of a
      bandgap in their bulk and gapless Dirac fermions at their surfaces. New physical
      phenomena originating from the presence of the Dirac fermions are predicted to
      occur, and to be experimentally accessible via transport measurements in suitably
      designed electronic devices. Here we study transport through superconducting
      junctions fabricated on thin Bi(2)Se(3) single crystals, equipped with a gate
      electrode. In the presence of perpendicular magnetic field B, sweeping the gate
      voltage enables us to observe the filling of the Dirac fermion Landau levels,
      whose character evolves continuously from electron- to hole-like. When B=0, a
      supercurrent appears, whose magnitude can be gate tuned, and is minimum at the
      charge neutrality point determined from the Landau level filling. Our results
      demonstrate how gated nano-electronic devices give control over normal and
      superconducting transport of Dirac fermions at an individual surface of a three
      dimensional topological insulators.

PMID- 22146395
TI  - Activin enhances skin tumourigenesis and malignant progression by inducing a pro
      tumourigenic immune cell response.
AB  - Activin is an important orchestrator of wound repair, but its potential role in
      skin carcinogenesis has not been addressed. Here we show using different types of
      genetically modified mice that enhanced levels of activin in the skin promote
      skin tumour formation and their malignant progression through induction of a pro
      tumourigenic microenvironment. This includes accumulation of tumour-promoting
      Langerhans cells and regulatory T cells in the epidermis. Furthermore, activin
      inhibits proliferation of tumour-suppressive epidermal gammadelta T cells,
      resulting in their progressive loss during tumour promotion. An increase in
      activin expression was also found in human cutaneous basal and squamous cell
      carcinomas when compared with control tissue. These findings highlight the
      parallels between wound healing and cancer, and suggest inhibition of activin
      action as a promising strategy for the treatment of cancers overexpressing this
      factor.

PMID- 22146396
TI  - Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell
      adhesion.
AB  - Multiple surface envelope proteins are involved in the human herpes simplex virus
      type 1 entry and fusion. Among them, glycoprotein D (gD) has an important role by
      binding to the host receptors such as herpes virus entry mediator and nectin-1.
      Although the complex structure of gD with herpes virus entry mediator has been
      established, the binding mode of gD with the nectin-1 is elusive. Nectin-1 is a
      member of the immunoglobulin (Ig)-like (three Ig-like domains) cell adhesion
      molecules and is believed to form a homodimer to exert its functions. Here we
      report the complex structure of gD and nectin-1 (three Ig domains), revealing
      that gD binds the first Ig domain of nectin-1 in a similar mode to the nectin-1
      homodimer interaction. The key amino acids responsible for nectin-1 dimerization
      are also used for gD/nectin-1 binding. This result indicates that binding of gD
      to nectin-1 would preclude the nectin-1 dimerization, consequently abolishing its
      cell adhesion function.

PMID- 22146397
TI  - Low-concentration mechanical biosensor based on a photonic crystal nanowire
      array.
AB  - The challenge for new biosensors is to achieve detection of biomolecules at low
      concentrations, which is useful for early-stage disease detection. Nanomechanical
      biosensors are promising in medical diagnostic applications. For nanomechanical
      biosensing at low concentrations, a sufficient resonator device surface area is
      necessary for molecules to bind to. Here we present a low-concentration (500 aM
      sensitivity) DNA sensor, which uses a novel nanomechanical resonator with ordered
      vertical nanowire arrays on top of a Si/SiO(2) bilayer thin membrane. The high
      sensitivity is achieved by the strongly enhanced total surface area-to-volume
      ratio of the resonator (10(8) m(-1)) and the state-of-the-art mass-per-area
      resolution (1.8*10(-12) kg m(-2)). Moreover, the nanowire array forms a photonic
      crystal that shows strong light trapping and absorption over broad-band optical
      wavelengths, enabling high-efficiency broad-band opto-thermo-mechanical remote
      device actuation and biosensing on a chip. This method represents a mass-based
      platform technology that can sense molecules at low concentrations.

PMID- 22146398
TI  - Plasmon resonance enhanced multicolour photodetection by graphene.
AB  - Graphene has the potential for high-speed, wide-band photodetection, but only
      with very low external quantum efficiency and no spectral selectivity. Here we
      report a dramatic enhancement of the overall quantum efficiency and spectral
      selectivity that enables multicolour photodetection, by coupling graphene with
      plasmonic nanostructures. We show that metallic plasmonic nanostructures can be
      integrated with graphene photodetectors to greatly enhance the photocurrent and
      external quantum efficiency by up to 1,500%. Plasmonic nanostructures of variable
      resonance frequencies selectively amplify the photoresponse of graphene to light
      of different wavelengths, enabling highly specific detection of multicolours.
      Being atomically thin, graphene photodetectors effectively exploit the local
      plasmonic enhancement effect to achieve a significant enhancement factor not
      normally possible with traditional planar semiconductor materials.

PMID- 22146399
TI  - Spin waves and magnetic exchange interactions in insulating
      Rb(0.89)Fe(1.58)Se(2).
AB  - The parent compounds of iron pnictide superconductors are bad metals with a
      collinear antiferromagnetic structure and Neel temperatures below 220 K. Although
      alkaline iron selenide A(y)Fe(1.6+x)Se(2) (A=K, Rb, Cs) superconductors are
      isostructural with iron pnictides, in the vicinity of the undoped limit they are
      insulators, forming a block antiferromagnetic order and having Neel temperatures
      of roughly 500 K. Here we show that the spin waves of the insulating
      antiferromagnet Rb(0.89)Fe(1.58)Se(2) can be accurately described by a local
      moment Heisenberg Hamiltonian. A fitting analysis of the spin wave spectra
      reveals that the next-nearest neighbour couplings in Rb(0.89)Fe(1.58)Se(2),
      (Ba,Ca,Sr)Fe(2)As(2), and Fe(1.05)Te are of similar magnitude. Our results
      suggest a common origin for the magnetism of all the Fe-based superconductors,
      despite having different ground states and antiferromagnetic orderings.

PMID- 22146400
TI  - A complex multi-notch astronomical filter to suppress the bright infrared sky.
AB  - A long-standing and profound problem in astronomy is the difficulty in obtaining
      deep near-infrared observations due to the extreme brightness and variability of
      the night sky at these wavelengths. A solution to this problem is crucial if we
      are to obtain the deepest possible observations of the early Universe, as
      redshifted starlight from distant galaxies appears at these wavelengths. The
      atmospheric emission between 1,000 and 1,800 nm arises almost entirely from a
      forest of extremely bright, very narrow hydroxyl emission lines that varies on
      timescales of minutes. The astronomical community has long envisaged the prospect
      of selectively removing these lines, while retaining high throughput between
      them. Here we demonstrate such a filter for the first time, presenting results
      from the first on-sky tests. Its use on current 8 m telescopes and future 30 m
      telescopes will open up many new research avenues in the years to come.

PMID- 22146401
TI  - Association of nitrogen compounds in drinking water with incidence of esophageal
      squamous cell carcinoma in Shexian, China.
AB  - The incidence of esophageal squamous cell carcinoma (ESCC), which is the eighth
      most common malignancy worldwide, is highest in China.  The purpose of this study
      was to investigate the association between nitrogen compounds in drinking water
      with the incidence of ESCC by geographical spatial analysis.  The incidence of
      ESCC is high in Shexian county, China, and environmental factors, particularly
      nitrogen-contaminated drinking water, are the main suspected risk factors.  This
      study focuses on three nitrogen compounds in drinking water, namely, nitrates,
      nitrites, and ammonia, all of which are derived mainly from domestic garbage and
      agricultural fertilizer.  The study surveyed 48 villages in the Shexian area with
      a total population of 54,716 (661 adults with ESCC and 54,055 non-cancer
      subjects).  Hot-spot analysis was used to identify spatial clusters with a high
      incidence of ESCC and a high concentration of nitrogen compounds.  Logistic
      regression analysis was used to detect risk factors for ESCC incidence.  Most
      areas with high concentrations of nitrate nitrogen in drinking water had a high
      incidence of ESCC.  Correlation analysis revealed a significant positive
      relationship between nitrate concentration and ESCC (P = 0.01).  Logistic
      regression analysis also confirmed that nitrate nitrogen has a significantly
      higher odds ratio.  The results indicate that nitrate nitrogen is associated with
      ESCC incidence in Shexian county.  In conclusion, high concentrations of nitrate
      nitrogen in drinking water may be a significant risk factor for the incidence of
      ESCC.

PMID- 22146402
TI  - Editorial highlighted meetings series: Asian Society for Vascular Biology 2010.

PMID- 22146403
TI  - Functional characterization of transmembrane intracellular pH regulators and
      mechanism of alcohol-induced intracellular acidosis in human umbilical cord blood
      stem cell-like cells.
AB  - Changing intracellular pH (pHi) exerts considerable influence on many cellular
      functions. Different pHi regulators, such as the Na-H exchanger (NHE),
      Na/(Equation is included in full-text article.)symporter, and Cl/OH exchanger
      (CHE), have been identified in mature mammalian cells. The aims of the present
      study were to investigate the physiological mechanisms of pHi recovery and to
      further explore the effects of alcohol on the pHi in human umbilical cord blood
      CD34 stem cell-like cells (HUCB-CD34STs). HUCB-CD34STs were loaded with the pH
      sensitive dye, 2',7'-bis(2-carboxethyl)-5(6)-carboxyfluorescein, to examine pHi.
      In isolated HUCB-CD34STs, we found that (1) the resting pHi is 7.03 +/- 0.02; (2)
      2 Na-dependent acid extruders and a Cl-dependent acid loading carrier exist and
      are functional; (3) alcohol functions in a concentration-dependent manner to
      reduce pHi and increase NHE activity, but it does not affect CHE activity; and
      (4) fomepizole, a specific alcohol dehydrogenase inhibitor, does not change the
      intracellular acidosis and NHE activity-induced by alcohol, whereas 3-amino-1,
      2,4-trizole, a specific catalase inhibitor, entirely abolishes these effects. In
      conclusion, we demonstrate that 2 acid extruders and 1 acid loader (most likely
      NHE, NBC, and CHE, respectively) functionally existed in HUCB-CD34STs.
      Additionally, the intracellular acidosis is mainly caused by catalase-mediated
      alcohol metabolites, which provoke the activity of NHE.

PMID- 22146404
TI  - Different K+ channels are involved in relaxation of arterial and venous graft
      induced by nicorandil.
AB  - The drug nicorandil is a vasodilator approved for the treatment of angina. In
      addition to its well-known effect on the opening of ATP-sensitive K (KATP)
      channels, nicorandil-induced vasorelaxation also involves the opening of Ca
      activated K channels. The aim of this study was to investigate the effects of
      nicorandil on the isolated human internal mammary artery (HIMA) and the human
      saphenous vein (HSV) and to define the contribution of different K channel
      subtypes in the nicorandil action on these arterial and venous grafts. Our
      results show that nicorandil induced a concentration-dependent relaxation of HSV
      and HIMA rings precontracted by phenylephrine. Glibenclamide, a selective KATP
      channels inhibitor, partially inhibited the response to nicorandil in both HSV
      and HIMA. Iberiotoxin, a most selective blocker of large-conductance Ca-activated
      K (BKCa) channels, partly antagonized relaxation of HIMA. A nonselective blocker
      of voltage-gated K channels, 4-aminopyridine caused partial inhibition of the
      nicorandil-induced relaxation of HSV but did not antagonize relaxation of HIMA
      induced by nicorandil. Margatoxin, a potent inhibitor of KV1.3 channels, did not
      abolish the effect of nicorandil on HSV and HIMA. Our results showed that
      nicorandil induced strong endothelium-independent relaxation of HSV and HIMA
      contracted by phenylephrine. It seems that KATP and 4-aminopyridine-sensitive K
      channels located in the smooth muscle of HSV mediated relaxation induced by
      nicorandil. In addition, KATP and BKCa channels are probably involved in the
      nicorandil action on HIMA.

PMID- 22146405
TI  - The effect of endothelial progenitor cells on angiotensin II-induced
      proliferation of cultured rat vascular smooth muscle cells.
AB  - Previous studies have demonstrated that endothelial progenitor cells (EPCs) could
      delay the progress of vascular remodeling in blood vessel-proliferating diseases.
      The proliferation of vascular smooth muscle cells (VSMCs) is a pivotal factor in
      cardiovascular diseases. In this study, we investigated whether EPCs could
      inhibit the Angiotensin II (Ang II)-induced proliferation of VSMCs. The effect of
      early EPC-conditioned medium (E-EPC-CM), late EPCs-CM (L-EPC-CM), and HUVEC-CM on
      Ang II-induced proliferation of VSMCs was assessed by BrdU incorporation, total
      protein content, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assays, and flow cytometry. Reverse transcriptase-polymerase chain reaction and
      Western blot were performed to analyze the effect of different CMs on Ang II
      induced phosphorylations of ERK, JNK, p38, and NF-kappaB subunit p65 and the
      expressions of c-myc and c-fos. E-EPC-CM, L-EPC-CM, and HUVEC-CM significantly
      inhibited the Ang II-induced DNA synthesis, total protein expression, cell
      survival, and cell cycle progress of VSMCs. Furthermore, E-EPC-CM significantly
      inhibited the Ang II-induced phosphorylation of ERK, JNK, p38, and p65 (nuclear
      translocation of p65) and the expressions of c-myc and c-fos. Taken together,
      these data suggested that EPCs may delay the progress of vascular remodeling in
      blood vessel-proliferating diseases by inhibiting Ang II-induced proliferation of
      VSMCs through inactivating MAPKs and NF-kappaB signaling pathways and by reducing
      the expressions of c-myc and c-fos.

PMID- 22146406
TI  - Therapeutic potential of fucoidan in myocardial ischemia.
AB  - Fucoidan, a sulfated polysaccharide extracted from brown seaweed, is a candidate
      for the treatment of ischemic diseases. The aim of this study was to measure the
      therapeutic potential of fucoidan in a rat model of myocardial ischemia
      reperfusion injury. Forty rats were submitted to myocardial ischemia-reperfusion
      injury by transient occlusion of the left coronary artery. Rats were then
      randomized into 2 groups: fucoidan (5 mg/kg, intramuscularly; n = 20) or control
      (saline intramuscularly; n = 20) was administered 1 hour before injury and daily
      thereafter for 1 month. At 1 month, plasma levels of stromal cell-derived factor
      1alpha (SDF-1alpha) were assessed by enzyme-linked immunosorbent assay kit.
      Hearts were evaluated by histoimmunochemistry. Fucoidan induced significant
      antifibrotic effects, reducing the infarct scar size by almost 30% on Sirius red
      stained sections (9.45% +/- 4.27% vs. 13% +/- 5.67% in controls; P = 0.03).
      Vascular density in the fucoidan group (alpha-actin, RECA-1, or lectin BS1
      stained) was increased by 40% (2.18 +/- 0.79 mm vs. 1.49 +/- 0.42 mm in controls
      *200; P = 0.001). Plasma SDF-1alpha at 1 month was not significantly different
      between the 2 groups. However, increased immunostaining density of SDF-1alpha and
      vascular endothelial growth factor in fibrotic ischemic tissues was observed in
      fucoidan-treated animals versus controls. In conclusion, fucoidan enhanced tissue
      repair in myocardial ischemia-reperfusion by promoting revascularization (in situ
      vascular endothelial growth factor and SDF-1alpha overexpression) and limiting
      fibrosis. Consequently, fucoidan may be useful for myocardial ischemic patients.

PMID- 22146407
TI  - Potential roles of PI3K/Akt and Nrf2-Keap1 pathways in regulating hormesis of Z
      ligustilide in PC12 cells against oxygen and glucose deprivation.
AB  - Many phytochemicals may ameliorate neurological disorders through a hormetic
      mechanism. The aim of this study was to characterize the hormetic role of Z
      ligustilide in PC12 cells against oxygen glucose deprivation (OGD) induced cell
      death. We examined the interactions of Z-ligustilide with the pro-survival
      signals mediated by phosphatidylinositol 3-kinase (PI3K) and transcription factor
      nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathways. We also
      investigated the effect of Z-ligustilide on the intracellular redox signaling
      system involving reactive oxygen species (ROS) and glutathione (GSH). Z
      ligustilide not only triggered stress response by causing ROS formation and
      transient GSH depletion, but also activated survival-promoting signals via cross
      talking of PI3K and Nrf2 pathways. A key finding was that Z-ligustilide
      preconditioning protected PC12 cells from OGD-induced injury either at a low
      concentration for a prolonged period of time or at a high concentration for a
      short period of time. Presumably, mild preconditioning stimulated moderate ROS
      production, but effectively activated hormetic signals and induced stress
      responsive genes. In contrast, higher concentrations of Z-ligustilide could be
      toxic over a prolonged period of time due to massive ROS production. These
      results suggest that the effect of Z-ligustilide may be regulated by a biphasic
      hormetic mechanism involving initial induction of oxidative stress and subsequent
      activation of stress response gene expression.

PMID- 22146408
TI  - Influence of genetic polymorphisms of xenobiotic metabolizing enzymes on the risk
      of developing leukemia in a Tunisian population.
AB  - Leukemia is a type of cancer of the blood or bone marrow that is characterized by
      an abnormal increase of white blood cells. Leukemia is clinically and
      pathologically subdivided into a variety of large groups. The risk of developing
      leukemia may be influenced by polymorphisms of xenobiotic metabolizing enzymes.
      In this work, we conduct a case-control study to assess the impact of
      polymorphisms in GSTM1, GSTT1 and NAT2 genes on the risk of developing leukemia.
      Our data have shown that GSTM1*0 and GSTT1*0 were respectively associated with
      2.05 and 4.36 increased risk for acute lymphoblastic leukemia (ALL). We have also
      shown that GSTM1*0 and GSTT1*0 act additively to increase the risk for ALL.
      Indeed, patients harbouring the "GSTM1*0/GSTT1*0" genotype were at 11.81-fold
      increased risk for developing ALL (P = 2 10(-5)). The risk for developing acute
      myeloid leukemia (AML) increases on patients with "rapid or intermediate NAT2
      genotypes". Finally, the comparison of leukemia subgroups according to GSTM1,
      GSTT1 and NAT2 genotypes, suggests that leukemogenesis of different leukemia
      subgroups is very distinct. In conclusion, our findings suggest that
      leukemogenesis is associated with carcinogen metabolism and consequently related
      to environmental exposures.

PMID- 22146409
TI  - Comparison of two dosing frequencies of subcutaneous interferon beta-1a in
      patients with a first clinical demyelinating event suggestive of multiple
      sclerosis (REFLEX): a phase 3 randomised controlled trial.
AB  - BACKGROUND: In patients presenting with a first clinical demyelinating event that
      is suggestive of multiple sclerosis (MS), treatment with interferon beta can
      delay the occurrence of further attacks and the onset of MS. We investigated the
      effects of two dosing frequencies of subcutaneous interferon beta-1a in patients
      with a first clinical demyelinating event. METHODS: We undertook a multicentre
      phase 3 study (REbif FLEXible dosing in early MS [REFLEX]) that included patients
      (aged 18-50 years) with a single clinical event suggestive of MS, and at least
      two clinically silent T2 lesions on brain MRI. Participants were randomly
      assigned in a 1:1:1 ratio by use of a centralised interactive voice response
      system to receive the serum-free formulation of subcutaneous interferon beta-1a
      44 MUg three times a week or once a week (plus placebo twice a week for masking),
      or placebo three times a week for up to 24 months. Patients and physicians were
      masked to group allocation. The primary endpoint was time to a diagnosis of MS as
      defined by the 2005 McDonald criteria and the main secondary endpoint was time to
      clinically definite MS (CDMS) as defined by the Poser criteria. Analysis was by
      intention to treat. The study is registered with ClinicalTrials.gov, number
      NCT00404352. FINDINGS: 517 patients were randomly assigned (171 to subcutaneous
      interferon beta-1a three times a week, 175 to subcutaneous interferon beta-1a
      once a week, and 171 to placebo) and 515 were treated. The 2-year cumulative
      probability of McDonald MS was significantly lower in patients treated with
      subcutaneous interferon beta-1a (three times a week 62.5%, p<0.0001, hazard ratio
      [HR] 0.49 [95% CI 0.38-0.64]; once a week 75.5%, p=0.008, HR 0.69 [0.54-0.87])
      versus placebo (85.8%). 2-year rates of conversion to CDMS were lower for both
      interferon beta-1a dosing regimens (three times a week 20.6%, p=0.0004, HR 0.48
      [0.31-0.73]; once a week 21.6%, p=0.0023, HR 0.53 [0.35-0.79]) than for placebo
      (37.5%). Adverse events were within the established profile for subcutaneous
      interferon beta-1a. INTERPRETATION: Both regimens of subcutaneous interferon beta
      1a delayed clinical relapses and subclinical disease activity. The potential
      differences between the regimens warrant longer-term study. FUNDING: Merck Serono
      SA, Geneva, Switzerland.

PMID- 22146410
TI  - The REFLEX study: a missed opportunity?

PMID- 22146411
TI  - A composite athletic tape with hyperelastic material properties improves and
      maintains ankle support during exercise.
AB  - STUDY DESIGN: Controlled laboratory testing using a single-group, prospective,
      repeated-measures design. OBJECTIVES: To compare the material properties of a
      hyperelastic athletic tape to a conventional tape and to compare the passive
      ankle support of these tapes before and after exercise. BACKGROUND: The near
      linear material properties of conventional athletic tape may interfere with ankle
      motion, resulting in reduced athletic performance. Conventional athletic tape is
      also known to lose much of its initial support during exercise. It was assumed
      that a tape constructed of Kevlar fibers embedded in a silicon matrix would
      possess hyperelastic material properties that would improve ankle support.
      METHODS: A tensile testing machine was used to determine the tensile material
      properties of 11 samples of conventional and hyperelastic tape. The ankles of 11
      young, healthy athletes were taped, one ankle with conventional tape and the
      other ankle with hyperelastic tape. The passive ankle support of each tape was
      measured with an instrumented linkage (the ankle flexibility tester) before and
      after 30 minutes of exercise. RESULTS: The composite tape had a significantly
      higher load to failure than the conventional tape. It had significantly lower
      initial stiffness and higher late stiffness than conventional tape, thus
      demonstrating highly hyperelastic behavior. The hyperelastic tape maintained a
      significantly higher portion of its support during the 30 minutes of exercise
      than the conventional tape. CONCLUSIONS: Composite athletic tape with highly
      hyperelastic properties can be constructed and maintains a larger portion of its
      support during short-duration exercises (less than 30 minutes) than conventional
      athletic tape.

PMID- 22146412
TI  - Current world literature.

PMID- 22146414
TI  - The phase transition in annealed mechanically alloyed Fe - Cu.
AB  - Using Mossbauer spectra and x-ray diffraction patterns, annealed mechanically
      alloyed Fe - Cu has been investigated in this paper. It is found that in
      [Formula: see text], after it has been milled, fcc-Cu has transformed into bcc
      Cu, and some Cu atoms have diffused into the Fe. After the alloy has subsequently
      been annealed, it is found that bcc-Cu has transformed back into fcc-Cu, while
      the Cu atoms in the Fe have been separated. In [Formula: see text], after being
      milled, an fcc-Fe-rich phase has been formed, and after the alloy has
      subsequently been annealed, this has transformed back to bcc-Fe. The shorter the
      milling time and the higher the annealing temperature, the faster the
      transformation. In [Formula: see text], after it has been annealed, the fcc-Fe
      rich phase has transformed to bcc-Fe also, and the fcc-Cu-rich phase remains when
      the annealing temperature increases. All of these results show that the fcc-Fe
      rich phase in the milled samples is a metastable phase - it will transform to
      stable bcc-Fe when it is annealed - while the long-milling-product fcc-Cu-rich
      phase is a stable phase.

PMID- 22146415
TI  - CO2-based tissue expansion: a study of initial performance in ovine subjects.
AB  - BACKGROUND: Tissue expanders are an essential reconstructive surgical tool
      commonly utilized in two-staged breast reconstruction. The current technology is
      limited primarily to saline expansion, which can be a long process requiring
      frequent office visits. Eliminating the need for percutaneous injections could
      potentially improve the psychological and physical discomfort associated with the
      expansion process as well as save time and resources for both the patient and
      surgeon. OBJECTIVES: The authors describe a novel system of gradual, controlled,
      needle-free expansion. The purpose of the study was to evaluate, prior to
      clinical use, the in vivo communication between CO(2)-based tissue expanders and
      their paired handheld dosage controllers and the ability of each expander to
      reach its intended volume. METHODS: Twelve expanders-three small (400 cm(3)),
      three medium (650 cm(3)), four large (850 cm(3)), and two full (1100 cm(3))-were
      implanted in two mature ovines and were expanded daily with CO(2) using 12 paired
      handheld dosage controllers. Device performance and expansion progress (cm(3)/d)
      to size-specified volumes were observed and recorded. An on-site veterinarian
      monitored the animals for signs of distress during and after inflations. After
      full expansion of the implants, the animals were euthanized and the implants were
      surgically removed and examined. RESULTS: All 12 paired devices performed to
      specification, achieving successful expansion, and measured volumes of explanted
      expanders confirmed expansion to the labeled volume. Expansion to full volume was
      achieved in all units in Ovine 1 within 13 days and in Ovine 2 within 11 days.
      Total implantation time was 21 days in Ovine 1 and 12 days in Ovine 2. No adverse
      events were encountered. CONCLUSIONS: This CO(2)-based tissue expansion system
      offers a novel and potentially valuable tool for reconstructive surgery. This
      study demonstrated the in vivo performance of a CO(2)-based tissue expander in an
      ovine model and merits future clinical research efforts. All tested devices
      accomplished needle-free expansion with the expanders responding to dosage
      controller commands within programmed safety limitations. This system has the
      potential to expedite expansion through gradual, controlled distention of tissue
      and to simplify the process for both physician and patient.

PMID- 22146416
TI  - The inverted-v chevron umbilicoplasty for breast reconstruction and
      abdominoplasty.
AB  - The umbilicoplasty is a key component of abdominoplasty and closure of autologous
      abdominal wall donor sites in breast reconstruction (TRAM/DIEP). The
      aesthetically-pleasing umbilicus tends to be small and vertically-oriented in
      nature, with superior hooding and shadow, inferior retraction and slope, and
      positioning at the topmost level of the iliac crest. In this Featured Operative
      Technique, the authors describe their technique for performing an inverted-V
      chevron umbilicoplasty, which is their method of choice for restoring the
      umbilicus to an aesthetic and youthful appearance with minimal scarring.

PMID- 22146418
TI  - Epilepsy and celiac disease: review of literature.
AB  - Celiac disease (CD) is a chronic, immune-mediated disorder, characterized by
      small intestinal malabsorption of nutrients after the ingestion of gluten by
      genetically susceptible individuals. The discovery of the wide variations in the
      nature and intensity of clinical presentation of CD has transformed its status,
      long considered a rare disease, to that of a common health problem. As patients
      with CD get older, they tend to present with complaints not directly referable to
      the gastrointestinal tract. Neurologic symptoms, caused by lesions of the central
      or peripheral nervous system occasionally occur in patients with CD and are
      poorly understood. This review focalizes on the present knowledge of the
      potential relationship between CD and epilepsy. The prevalence of CD among
      patients with epilepsy is not homogeneously distributed, probably because
      epilepsy encompasses a heterogeneous group of disorders. In fact, the clinical
      spectrum of epilepsy related to CD ranges from benign syndromes to intractable
      epilepsy. The precise mechanism of the potential association between CD and
      epilepsy is also still under discussion.

PMID- 22146419
TI  - The medical management of epilepsy.
AB  - With many new medications on the market and new data about the various side
      effects of antiepilepsy drugs (AEDs), the medical management of epilepsy can seem
      unnecessarily complicated for the non-specialist. The process can be thought of
      taking place in 7 steps: 1) assessing the need for medications; 2) defining the
      seizures and classifying the epilepsy syndrome; 3) knowing which medications are
      best used in which syndromes; 4) taking into account patient priorities when
      choosing a medication, such as cotreatment or avoidance of neurobehavioral issues
      and weight loss or gain; 5) considering other life issues, such as planning a
      pregnancy and breastfeeding; 6) choosing a maintenance dose and deciding when to
      consider a change to another medication or to use dual therapy; and 7) if seizure
      free, which patients to consider AED reduction or withdrawal. The goal is simply,
      no seizures and no side-effects. Seizure freedom is an important goal to reduce
      injury, mortality and improve quality of life. Improving tolerability is equally
      as important, as both acute and chronic side-effects of AEDs can be as disabling
      as seizures themselves.

PMID- 22146420
TI  - Surgical successes and failures of invasive video-EEG monitoring in the
      presurgical evaluation of epilepsy.
AB  - Invasive monitoring with intracranial electrodes continues to play a critical
      role in the presurgical evaluation of patients with medically intractable
      epilepsy. Intracranial monitoring helps in localizing the epileptogenic zone and
      can be used to delineate eloquent cortical areas adjacent to this zone. In this
      review we analyzed surgical successes and failures of invasive video
      electroencephalography (EEG) monitoring. Thorough understanding of all potential
      complications is of paramount importance not only for detection and successful
      management of intractable epilepsy but also for medicolegal purposes, as patients
      and their relatives need to be fully informed about the possible risks associated
      with invasive monitoring. A mortality rate between 0.5% and 2.8% has been
      reported. Cerebrospinal fluid (CSF) leaks and infections are the most frequent
      complications, with an incidence ranging from 0-31.3% and from 0-17.4%,
      respectively. The incidence of intracranial hemorrhage is reported to be up to
      14% with subdural hematomas being the most prevalent. Epidural hematomas are less
      frequent and encountered in up to 2.6% of cases. Intraparenchymal hematomas are
      even less frequent and are typically associated with the placement of depth
      electrodes. In 47-98% of cases, invasive video-EEG monitoring results into
      resective surgery. Invasive video-EEG monitoring is a reasonably safe and
      effective method to help delineate the epileptogenic zone and its relation to
      eloquent cortex.

PMID- 22146421
TI  - Recognize and manage psychiatric comorbidities in patients with epilepsy.
AB  - The management of patients with epilepsy, especially those with drug refractory
      syndromes, may be complicated by psychiatric comorbidities that significantly
      affect prognosis, morbidity and mortality. In general terms, a careful
      distinction between true psychiatric manifestations and seizure-based phenomena
      (i.e. peri-ictal psychiatric symptoms) is crucial, having implications in terms
      of prognosis and treatment. Guidelines of treatment for psychiatric disorders in
      epilepsy are still lacking. In general terms, internationally adopted guidelines
      of treatment outside epilepsy may be considered taking into account a number of
      special issues related to the underlying brain disorder. New compounds are
      generally well tolerated and reasonably safe in patients with epilepsy. SSRIs,
      especially citalopram, are considered first line agents in mood and anxiety
      disorders and new antipsychotics, especially olanzapine, quetiapine and
      risperidone, in interictal psychoses. The potential for drug interactions is
      generally minimized although drug dosages need to be adjusted according to
      clinical response in patients taking inducers (e.g. carbamazepine, barbiturates
      or phenytoin). Long term tolerability need to be balanced with long term side
      effects such as weight gain and sedation. Comprehensive treatment of people with
      epilepsy requires that psychiatric comorbidities are recognized and taken into
      account in the overall management. Continued clinical research is needed to
      obtain further knowledge about the optimal use of the expanding antiepileptic
      armamentarium and on how to tailor treatment to each individual patient according
      to clinical circumstances.

PMID- 22146422
TI  - Influence of family history of NIDDM on basal metabolic rate in sedentary and
      active women.
AB  - AIM AND METHODS: The influence of family history of non-insulin-dependent
      diabetes (NIDDM) on basal metabolic rate (BMR) has been investigated in 116
      voluntarily women: 25 sedentary and 34 athletes without a family predisposition
      to type 2 diabetes (FH-); 21 sedentary and 15 athletes with a second degree
      predisposition to NIDDM (FH+); 10 sedentary and 11 athletes with a first degree
      predisposition to NIDDM (FH++). RESULTS: The results showed that family history
      on type 2 diabetes is strongly related to sedentary in women with significant
      high body weight values and an increased fat mass. There was no significant
      difference in the body parameters among the athletes groups, confirming the
      protective role of regular physical activity on these parameters. Analysing basal
      energy expenditure showed that sedentary FH++ women had a significant increase in
      BMR in absolute values; however there were no differences in BMR when reported to
      body weight and body fat-free mass. In contrast, the FH++ athletes group had
      lower BMR (absolute values) than the sedentary group. No differences were found
      in the relative BMR either. By comparing the recorded BMR of the groups with the
      theoretical values, it has been shown that the FH++ athletes had a reduced
      increase in BMR with respect to the other groups. The FH- athletes showed a
      higher energy turnover compared to the other women and relative to predicted
      values. CONCLUSION: This study confirms that family history of type 2 diabetes
      has an important influence on the phenotype of women and it can be associated
      with significant metabolic and anthropometric modifications in young healthy
      subjects. It may also account for changes in the body composition and basal
      metabolic rate alterations in subjects with a predisposition to type 2 diabetes,
      by reducing the metabolic basal output expected in active subjects.

PMID- 22146423
TI  - Ampicillin-based therapy for Helicobacter pylori eradication.

PMID- 22146424
TI  - Inner ear morphological correlates of ultrasonic hearing in frogs.
AB  - Three species of anuran amphibians (Odorrana tormota, Odorrana livida and Huia
      cavitympanum) have recently been found to detect ultrasounds. We employed
      immunohistochemistry and confocal microscopy to examine several morphometrics of
      the inner ear of these ultrasonically sensitive species. We compared
      morphological data collected from the ultrasound-detecting species with data from
      Rana pipiens, a frog with a typical anuran upper cut-off frequency of ~3 kHz. In
      addition, we examined the ears of two species of Lao torrent frogs, Odorrana
      chloronota and Amolops daorum, that live in an acoustic environment approximating
      those of ultrasonically sensitive frogs. Our results suggest that the three
      ultrasound-detecting species have converged on small-scale functional
      modifications of the basilar papilla (BP), the high-frequency hearing organ in
      the frog inner ear. These modifications include: 1. reduced BP chamber volume, 2.
      reduced tectorial membrane mass, 3. reduced hair bundle length, and 4. reduced
      hair cell soma length. While none of these factors on its own could account for
      the US sensitivity of the inner ears of these species, the combination of these
      factors appears to extend their hearing bandwidth, and facilitate high
      frequency/ultrasound detection. These modifications are also seen in the ears of
      O. chloronota, suggesting that this species is a candidate for high-frequency
      hearing sensitivity. These data form the foundation for future functional work
      probing the physiological bases of ultrasound detection by a non-mammalian ear.

PMID- 22146425
TI  - Temporal modulation transfer functions in cochlear implantees using a method that
      limits overall loudness cues.
AB  - Temporal modulation transfer functions (TMTFs) were measured for six users of
      cochlear implants, using different carrier rates and levels. Unlike most previous
      studies investigating modulation detection, the experimental design limited
      potential effects of overall loudness cues. Psychometric functions (percent
      correct discrimination of modulated from unmodulated stimuli versus modulation
      depth) were obtained. For each modulation depth, each modulated stimulus was
      loudness balanced to the unmodulated reference stimulus, and level jitter was
      applied in the discrimination task. The loudness-balance data showed that the
      modulated stimuli were louder than the unmodulated reference stimuli with the
      same average current, thus confirming the need to limit loudness cues when
      measuring modulation detection. TMTFs measured in this way had a low-pass
      characteristic, with a cut-off frequency (at comfortably loud levels) similar to
      that for normal-hearing listeners. A reduction in level caused degradation in
      modulation detection efficiency and a lower-cut-off frequency (i.e. poorer
      temporal resolution). An increase in carrier rate also led to a degradation in
      modulation detection efficiency, but only at lower levels or higher modulation
      frequencies. When detection thresholds were expressed as a proportion of dynamic
      range, there was no effect of carrier rate for the lowest modulation frequency
      (50 Hz) at either level.

PMID- 22146426
TI  - The pacific chapter annual meeting of the undersea & hyperbaric medical society.
AB  - The following is the summary report on the UHMS Pacific Chapter Annual Meeting
      held in Long Beach in October 2010. The conference provided the latest updates on
      scientific, technical and organizational aspects of Hyperbaric and Diving
      Medicine. Invited speakers gave series of lectures dealing with current standards
      of clinical practice and presenting the results of laboratory investigations with
      particular emphasis on mechanisms of hyperbaric oxygen therapy. Scientific
      sessions were accompanied by vendor exhibits and social events.

PMID- 22146427
TI  - Hydrogen is neuroprotective against surgically induced brain injury.
AB  - BACKGROUND: Neurosurgical operations cause unavoidable damage to healthy brain
      tissues. Direct surgical injury as well as surgically induced oxidative stress
      contributes to the subsequent formation of brain edema. Therefore, we tested the
      neuroprotective effects of hydrogen (H2) in an established surgical brain injury
      (SBI) model in rats. MATERIALS AND METHODS: Adult male Sprague - Dawley rats
      (weight 300-350g) were divided into three groups to serve as sham operated, SBI
      without treatment, and SBI treated with H2 (2.9%). Brain water content,
      myeloperoxidase (MPO) assay, lipid peroxidation (LPO), and neurological function
      were measured at 24 hrs after SBI. RESULTS: SBI resulted in localized brain edema
      (p = < 0.001). Hydrogen (2.9%) administered concurrently with surgery
      significantly decreased the formation of cerebral edema (p = 0.028) and improved
      neurobehavioral score (p = 0.022). However, hydrogen treatment failed to reduce
      oxidative stress (LPO assay) or inflammation (MPO assay) in brain tissues.
      CONCLUSIONS: Hydrogen appears to be promising as an effective, yet inexpensive
      way to reduce cerebral edema caused by surgical procedures. Hydrogen has the
      potential to improve clinical outcome, decrease hospital stay, and reduce overall
      cost to patients and the health care system.

PMID- 22146429
TI  - Reaction to retractions.

PMID- 22146430
TI  - Trial networks move beyond single-disease strategies.

PMID- 22146428
TI  - Diseases in a dish: modeling human genetic disorders using induced pluripotent
      cells.
AB  - The derivation of induced pluripotent cells (iPSCs) from individuals suffering
      from genetic syndromes offers new opportunities for basic research into these
      diseases and the development of therapeutic compounds. iPSCs can self renew and
      can be differentiated to many cell types, offering a potentially unlimited source
      of material for study. In this review we discuss the conceptual and practical
      issues to consider when attempting to model genetic diseases using iPSCs.

PMID- 22146431
TI  - New HCV drugs trigger race for more tolerable therapies.

PMID- 22146432
TI  - Institutes unite to put New York on the biopharma map.

PMID- 22146433
TI  - Genome center's location stuck in transit.

PMID- 22146434
TI  - Four-in-one HIV pill may be exception among combination drugs.

PMID- 22146435
TI  - Class of once-weekly diabetes drugs poised for approval.

PMID- 22146436
TI  - Patent-sharing scheme for neglected diseases may have catch.

PMID- 22146438
TI  - International coding upgrade affects clinical research and reviews.

PMID- 22146439
TI  - Biostatisticians call for more scientifically rigorous pilot studies.

PMID- 22146440
TI  - Databases aim to bridge the East-West divide of drug discovery.

PMID- 22146442
TI  - Straight talk with... Amanda Glassman by Dolgin Elie.

PMID- 22146443
TI  - Efficient drug approval and monitoring must rely on sound regulatory science.

PMID- 22146444
TI  - Breaking the silence.

PMID- 22146445
TI  - 2011 in review.

PMID- 22146447
TI  - Notable advances 2011.

PMID- 22146448
TI  - Drugs in traffic: the road to approval.

PMID- 22146450
TI  - A retrospective of retractions: the striking record in 2011.

PMID- 22146452
TI  - Mannose-binding lectin-the forgotten molecule?

PMID- 22146454
TI  - A gut triumvirate rules homeostasis.

PMID- 22146455
TI  - A sweet T cell response.

PMID- 22146456
TI  - Stressed tumor cell, chemosensitized cancer.

PMID- 22146457
TI  - NF-kappaB in DCs: it takes effort to be immature.

PMID- 22146458
TI  - Nitrite-NO bailout for a NOS complex too big to fail.

PMID- 22146459
TI  - Diagnosis in a dish: your skin can help your brain.

PMID- 22146460
TI  - Mixed results for a malaria vaccine.

PMID- 22146461
TI  - Fruitful progress to fertility: preserving oocytes from chemodestruction.

PMID- 22146462
TI  - Fruitful progress to fertility: male fertility in the test tube.

PMID- 22146467
TI  - Improving the efficacy of translational medicine by optimally integrating health
      care, academia and industry.

PMID- 22146474
TI  - Unraveling the human dendritic cell phagosome proteome by organellar enrichment
      ranking.
AB  - Dendritic cells (DC) take up pathogens through phagocytosis and process them into
      protein and lipid fragments for presentation to T cells. So far, the proteome of
      the human DC phagosome, a detrimental compartment for antigen processing and
      presentation as well as for DC activation, remains largely uncharacterized. Here
      we have analyzed the protein composition of phagosomes from human monocyte
      derived DC. For LC-MS/MS analysis we purified phagosomes from DC using latex
      beads targeted to DC-SIGN, and quantified proteins using a label-free method. We
      used organellar enrichment ranking (OER) to select proteins with a high potential
      to be relevant for phagosome function. The method compares phagosome protein
      abundance with protein abundance in whole DC. Phagosome enrichment indicates
      specific recruitment to the phagosome rather than co-purification or passive
      incorporation. Using OER we extracted the most enriched proteins that we further
      complemented with functionally associated proteins to define a set of 90
      phagosomal proteins that included many proteins with established relevance on DC
      phagosomes as well as high potential novel candidates. We already experimentally
      confirmed phagosomal recruitment of Galectin-9, which has not been previously
      associated with phagocytosis, to both bead and pathogen containing phagosomes,
      suggesting a role for Galectin-9 in DC phagocytosis.

PMID- 22146473
TI  - A proteomic approach to identification of plutonium-binding proteins in mammalian
      cells.
AB  - Plutonium can enter the body through different routes and remains there for
      decades; however its specific biochemical interactions are poorly defined. We,
      for the first time, have studied plutonium-binding proteins using a
      metalloproteomic approach with rat PC12 cells. A combination of immobilized metal
      ion chromatography, 2D gel electrophoresis, and mass spectrometry was employed to
      analyze potential plutonium-binding proteins. Our results show that several
      proteins from PC12 cells show affinity towards Pu(4+)-NTA (plutonium bound to
      nitrilotriacetic acid). Proteins from seven different spots in the 2D gel were
      identified. In contrast to the previously known plutonium-binding proteins
      transferrin and ferritin, which bind ferric ions, most identified proteins in our
      experiment are known to bind calcium, magnesium, or divalent transition metal
      ions. The identified plutonium interacting proteins also have functional roles in
      downregulation of apoptosis and other pro-proliferative processes. MetaCoreTM
      analysis based on this group of proteins produced a pathway with a statistically
      significant association with development of neoplastic diseases.

PMID- 22146475
TI  - Protein repertoire impact of Ubiquitin-Proteasome System impairment: insight into
      the protective role of beta-estradiol.
AB  - The Ubiquitin-Proteasome System (UPS) and the Autophagy-Lysosome Pathways (ALP)
      are key mechanisms for cellular homeostasis sustenance and protein clearance. A
      wide number of Neurodegenerative Diseases (NDs) are tied with UPS impairment and
      have been also described as proteinopathies caused by aggregate-prone proteins,
      not efficiently removed by proteasome. Despite the large knowledge on proteasome
      biological role, molecular mechanisms associated with its impairment are still
      blur. We have pursued a comprehensive proteomic investigation to evaluate the
      phenotypic rearrangements in protein repertoires associated with a UPS blockage.
      Different functional proteomic approaches have been employed to tackle UPS
      impairment impact on human NeuroBlastoma (NB) cell lines responsive to proteasome
      inhibition by Epoxomicin. 2-Dimensional Electrophoresis (2-DE) separation
      combined with Mass Spectrometry and Shotgun Proteomics experiments have been
      employed to design a thorough picture of protein profile. Unsupervised meta
      analysis of the collected proteomic data revealed that all the identified
      proteins relate each other in a functional network centered on beta-estradiol.
      Moreover we showed that treatment of cells with beta-estradiol resulted in
      aggregate removal and increased cell survival due to activation of the autophagic
      pathway. Our data may provide the molecular basis for the use of beta-estradiol
      in neurodegenerative disorders by induction of protein aggregate removal.

PMID- 22146476
TI  - The use of multiplexed MRM for the discovery of biomarkers to differentiate iron
      deficiency anemia from anemia of inflammation.
AB  - In this study we demonstrate the use of a multiplexed MRM-based assay to
      distinguish among normal (NL) and iron-metabolism disorder mouse models,
      particularly, iron-deficiency anemia (IDA), inflammation (INFL), and inflammation
      and anemia (INFL+IDA). Our initial panel of potential biomarkers was based on the
      analysis of 14 proteins expressed by candidate genes involved in iron transport
      and metabolism. Based on this study, we were able to identify a panel of 8
      biomarker proteins: apolipoprotein A4 (APO4), transferrin, transferrin receptor
      1, ceruloplasmin, haptoglobin, lactoferrin, hemopexin, and matrix
      metalloproteinase-8 (MMP8) that clearly distinguish among the normal and disease
      models. Within this set of proteins, transferrin showed the best individual
      classification accuracy over all samples (72%) and within the NL group (94%).
      Compared to the best single-protein biomarker, transferrin, the use of the
      composite 8-protein biomarker panel improved the classification accuracy from 94%
      to 100% in the NL group, from 50% to 72% in the INFL group, from 66% to 96% in
      the IDA group, and from 79% to 83% in the INFL+IDA group. Based on these
      findings, validation of the utility of this potentially important biomarker panel
      in human samples in an effort to differentiate IDA, inflammation, and
      combinations thereof, is now warranted. This article is part of a Special Section
      entitled: Understanding genome regulation and genetic diversity by mass
      spectrometry.

PMID- 22146477
TI  - Quantitative proteomic analysis of lignocellulolytic enzymes by Phanerochaete
      chrysosporium on different lignocellulosic biomass.
AB  - Lignocellulosic biomass from agricultural crop residues and forest waste
      represents an abundant renewable resource for bioenergy and future biofuel. The
      current bottleneck of lignocellulosic biofuel production is the hydrolysis of
      biomass to sugar. To understand the enzymatic hydrolysis of complex biomasses, in
      this report, lignocellulolytic enzymes secretion by Phanerochaete chrysosporium
      cultivated in different natural lignocellulosic biomass such as corn stover, hay,
      sawdust, sugarcane baggase, wheat bran and wood chips were quantitatively
      analyzed with the iTRAQ technique using LC-MS/MS. A diverse groups of enzymes,
      including cellulases, glycoside hydrolases, hemicellulases, lignin degrading
      enzymes, peroxidases, esterases, lipases, chitinases, peptidases, protein
      translocating transporter and hypothetical proteins were quantified, of which
      several were novel lignocellulosic biomass hydrolyzing enzymes. The quantitative
      expression and regulation of lignocellulolytic enzymes by P. chrysosporium were
      dependent on the nature and complexity of lignocellulosic biomass as well as
      physical size of the biomass. The iTRAQ data revealed oxidative and hydrolytic
      lignin degrading mechanism of P. chrysosporium. Numerous proteins presumed to be
      involved in natural lignocellulosic biomass transformation and degradation were
      expressed and produced in variable quantities in response to different
      agricultural and forest wastes.

PMID- 22146478
TI  - The effects of biological sex and gonadal hormones on learning strategy in adult
      rats.
AB  - When learning to navigate toward a goal in a spatial environment, rodents employ
      distinct learning strategies that are governed by specific regions of the brain.
      In the early stages of learning, adult male rats prefer a hippocampus-dependent
      place strategy over a striatum-dependent response strategy. Alternatively, female
      rats exhibit a preference for a place strategy only when circulating levels of
      estradiol are elevated. Notably, male rodents typically perform better than
      females on a variety of spatial learning tasks, which are mediated by the
      hippocampus. However, limited research has been done to determine if the
      previously reported male spatial advantage corresponds with a greater reliance on
      a place strategy, and, if the male preference for a place strategy is impacted by
      removal of testicular hormones. A dual-solution water T-maze task, which can be
      solved by adopting either a place or a response strategy, was employed to
      determine the effects of biological sex and hormonal status on learning strategy.
      In the first experiment, male rats made more correct arm choices than female rats
      during training and exhibited a bias for a place strategy on a probe trial. The
      results of the second experiment indicated that testicular hormones modulated arm
      choice accuracy during training, but not the preference for a place strategy.
      Together, these findings suggest that the previously reported male spatial
      advantage is associated with a greater reliance on a place strategy, and that
      only performance during the training phase of a dual-solution learning task is
      impacted by removal of testicular hormones.

PMID- 22146479
TI  - Photoluminescence band at 4.4 eV in oxygen-deficient silica: temperature effects.
AB  - We report experimental results on the spectral properties and time behaviour of
      the 4.4 eV photoluminescence (PL) band in oxygen-deficient silica [Formula: see
      text]. Our measurements, performed both at T = 300 K and T = 10 K, show that at
      room temperature the PL features are independent of the particular excitation
      energy (5.0 eV, 6.8 eV and 7.6 eV) whereas at low temperature, upon excitation at
      7.6 eV, the decay of the PL emission is faster than for lower excitation
      energies. This shortening of the PL lifetime is consistent with previously
      reported data, which were explained by hypothesizing an interconversion mechanism
      between two structural configurations of the same oxygen defect. Nevertheless,
      our results do not support the proposed mechanism and we tentatively suggest a
      different interpretation of the experimental data.

PMID- 22146480
TI  - Epithelial and stromal developmental patterns in a novel substitute of the human
      skin generated with fibrin-agarose biomaterials.
AB  - Development of human skin substitutes by tissue engineering may offer new
      therapeutic alternatives to the use of autologous tissue grafts. For that reason,
      it is necessary to investigate and develop new biocompatible biomaterials that
      support the generation of a proper human skin construct. In this study, we
      generated a novel model of bioengineered human skin substitute using human cells
      obtained from skin biopsies and fibrin-agarose biomaterials and we evaluated this
      model both at the ex vivo and the in vivo levels. Once the dermal fibroblasts and
      the epithelial keratinocytes were isolated and expanded in culture, we used
      fibrin-agarose scaffolds for the development of a full-thickness human skin
      construct, which was evaluated after 1, 2, 3 and 4 weeks of development ex vivo.
      The skin substitutes were then grafted onto immune-deficient nude mice and
      analyzed at days 10, 20, 30 and 40 postimplantation using transmission electron
      microscopy, histochemistry and immunofluorescence. The results demonstrated that
      the fibrin-agarose artificial skin had adequate biocompatibility and proper
      biomechanical properties. A proper development of both the bioengineered dermis
      and epidermis was found after 30 days in vivo, although the tissues kept ex vivo
      and those implanted in the animal model for 10 or 20 days showed lower levels of
      differentiation. In summary, our model of fibrin-agarose skin equivalent was able
      to reproduce the structure and histological architecture of the native human
      skin, especially after long-term in vivo implantation, suggesting that these
      tissues could reproduce the native skin.

PMID- 22146481
TI  - Expression of peroxisome proliferator activator receptor beta/delta
      (PPARbeta/delta) in acne vulgaris.
AB  - Sebum production is the key factor in the pathophysiology of acne. Studies in
      sebocyte and human sebaceous gland biology indicate that agonists of peroxisome
      proliferator-activated receptors (PPARs) alter sebaceous lipid production. Our
      objective was to detect the expression of PPARbeta/delta in acne lesions and find
      its contribution to disease pathogenesis. Twenty five acne vulgaris patients (14
      males, 11 females) were included. In addition, 12 healthy volunteers (6 males, 6
      females) served as controls. Punch biopsies (3mm) were taken from lesional skin
      of all patients, non-lesional skin in 12 patients, and from the healthy controls.
      The biopsies were estimated quantitatively for the level of PPARbeta/delta mRNA
      using reverse transcriptase-polymerase chain (RT-PCR) technique. PPARbeta/delta
      mRNA levels were significantly higher in patients than controls (p=0.00) and in
      patients' lesional than non-lesional skin (p=0.00). No significant difference
      however, was found between inflammatory and non-inflammatory lesions. Age and
      disease duration had no influence on mean PPAR mRNA levels in lesional skin.
      PPARbeta/delta is over expressed-in inflammatory and non-inflammatory acne
      vulgaris and may well be considered as a candidate target in future acne therapy.
      However, elucidation of its functional role is recommended.

PMID- 22146482
TI  - Increasing resistance of the Liverpool Epidemic Strain (LES) of Pseudomonas
      aeruginosa (Psa) to antibiotics in cystic fibrosis (CF)--a cause for concern?
AB  - BACKGROUND: Transmissible Pseudomonas aeruginosa (Psa) strains such as the
      Liverpool Epidemic Strain (LES) are now widespread throughout UK CF clinics:
      their susceptibility to antibiotics is therefore important. To study this, we
      compared antibiogram patterns of Psa strains in our CF clinic over 5 years,
      looking at differences in resistance patterns between strains and changes to
      these over time. METHODS: The antibiograms of sputum samples between 2004 and
      2008 from patients attending our centre were included. We compared Psa isolate
      antibiotic resistance (to six anti-pseudomonal antibiotics) patterns for patients
      infected with LES with those infected with other Psa strains, both in the total
      population in 2004 (125 patients) and 2008 (166 patients) and also longitudinally
      from annual review samples 2004 to 2008 in matched and unmatched patient groups.
      RESULTS: LES exhibited significantly more resistant isolates in 2004 (p<0.0001).
      There was an increase in antibiotic resistance in both LES and other Psa strains
      over time (p<0.001). Cox proportional hazards analysis of both unmatched (n=125)
      and matched (n=56) patients in 2004 revealed that LES infected patients were more
      likely to develop antibiotic resistant isolates over time (hazard ratio 8.1,
      p<0.001). Fewer LES isolates were classed as fully sensitive in both matched and
      unmatched groups at the end of study period (p<0.001). CONCLUSION: This study
      shows a worrying trend in antibiotic resistance in the Psa isolates amongst
      patients chronically infected with LES. This highlights the need to prevent cross
      infection through segregation and also the need to develop new strategies to
      treat these organisms.

PMID- 22146483
TI  - Carbon monoxide inhibits Fas activating antibody-induced apoptosis in endothelial
      cells.
AB  - BACKGROUND: The extrinsic apoptotic pathway initiates when a death ligand, such
      as the Fas ligand, interacts with its cell surface receptor (ie., Fas/CD95),
      forming a death-inducing signaling complex (DISC). The Fas-dependent apoptotic
      pathway has been implicated in several models of lung or vascular injury. Carbon
      monoxide, an enzymatic product of heme oxygenase-1, exerts antiapoptotic effects
      at low concentration in vitro and in vivo. METHODS: Using mouse lung endothelial
      cells (MLEC), we examined the antiapoptotic potential of carbon monoxide against
      apoptosis induced by the Fas/CD95-activating antibody (Jo2). Carbon monoxide was
      applied to cell cultures in vitro. The expression and/or activation of apoptosis
      related proteins and signaling intermediates were determined using Western
      Immunoblot and co-immunoprecipitation assays. Cell death was monitored by lactate
      dehydrogenase (LDH) release assays. Statistical significance was determined by
      student T-test and a value of P < 0.05 was considered significant. RESULTS:
      Treatment of MLEC with Fas-activating antibody (Jo2) induced cell death
      associated with the formation of the DISC, and activation of caspases (-8, -9,
      and -3), as well as the pro-apoptotic Bcl-2 family protein Bax. Exposure of MLEC
      to carbon monoxide inhibited Jo2-induced cell death, which correlated with the
      inhibition of DISC formation, cleavage of caspases-8, -9, and -3, and Bax
      activation. Carbon monoxide inhibited the phosphorylation of the Fas-associated
      death domain-containing protein, as well as its association with the DISC.
      Furthermore, carbon monoxide induced the expression of the antiapoptotic protein
      FLIP and increased its association with the DISC.CO-dependent cytoprotection
      against Fas mediated apoptosis in MLEC depended in part on activation of ERK1/2
      dependent signaling. CONCLUSIONS: Carbon monoxide has been proposed as a
      potential therapy for lung and other diseases based in part on its antiapoptotic
      effects in endothelial cells. In vitro, carbon monoxide may inhibit both
      Fas/caspase-8 and Bax-dependent apoptotic signaling pathways induced by Fas
      activating antibody in endothelial cells. Strategies to block Fas-dependent
      apoptotic pathways may be useful in development of therapies for lung or vascular
      disorders.

PMID- 22146485
TI  - Bulk modulus calculations based on perturbation self-consistency.
AB  - We propose a method for bulk modulus calculations of solids based on perturbation
      self-consistency within the local density functional. The essential assumption is
      that a finite scaling is applied to the one-electron wavefunction when the solid
      adjusts to a new distorted structure under pressure. Thus the one-electron
      potential of a deformed structure near equilibrium can be obtained by performing
      a scaling transformation to charge density directly. The method is formulated
      within the linear muffin-tin orbital method in the atomic sphere approximation
      and applied to the calculation of bulk moduli of [Formula: see text], FCC Al, BCC
      Li, [Formula: see text] and an ordered FCC [Formula: see text] superlattice. The
      bulk modulus calculated from a single self-consistency is in reasonably good
      agreement with that of a full self-consistent calculation. Our results for Al -
      Li systems confirm that the addition of lithium to FCC Al causes the bulk modulus
      to decrease.

PMID- 22146484
TI  - Histopathologic changes in the uterus, cervix and vagina of immature CD-1 mice
      exposed to low doses of perfluorooctanoic acid (PFOA) in a uterotrophic assay.
AB  - The estrogenic and antiestrogenic potential of perfluorooctanoic acid (PFOA) was
      assessed using an immature mouse uterotrophic assay and by histologic evaluation
      of the uterus, cervix and vagina following treatment. Female offspring of CD-1
      dams were weaned at 18days old and assigned to groups of equal weight, and
      received 0, 0.01, 0.1, or 1mg PFOA/kg BW/d by gavage with or without 17-beta
      estradiol (E(2), 500MUg/kg/d) from PND 18-20 (n=8/treatment/block). At 24h after
      the third dose (PND 21), uteri were removed and weighed. Absolute and relative
      uterine weights were significantly increased in the 0.01mg/kg PFOA only group.
      Characteristic estrogenic changes were present in all E(2)-treated mice; however,
      they were minimally visible in the 0.01 PFOA only mice. These data suggest that
      at a low dose PFOA produces minimal histopathologic changes in the reproductive
      tract of immature female mice, and does not antagonize the histopathologic
      effects of E(2).

PMID- 22146487
TI  - Moderately delayed post-insult treatment with normobaric hyperoxia reduces
      excitotoxin-induced neuronal degeneration but increases ischemia-induced brain
      damage.
AB  - BACKGROUND: The use and benefits of normobaric oxygen (NBO) in patients suffering
      acute ischemic stroke is still controversial. RESULTS: Here we show for the first
      time to the best of our knowledge that NBO reduces both NMDA-induced calcium
      influxes in vitro and NMDA-induced neuronal degeneration in vivo, but increases
      oxygen and glucose deprivation-induced cell injury in vitro and ischemia-induced
      brain damage produced by middle cerebral artery occlusion in vivo. CONCLUSIONS:
      Taken together, these results indicate that NBO reduces excitotoxin-induced
      calcium influx and subsequent neuronal degeneration but favors ischemia-induced
      brain damage and neuronal death. These findings highlight the complexity of the
      mechanisms involved by the use of NBO in patients suffering acute ischemic
      stroke.

PMID- 22146488
TI  - Positive effect of abdominal breathing exercise on gastroesophageal reflux
      disease: a randomized, controlled study.
AB  - OBJECTIVES: The lower esophageal sphincter (LES), surrounded by diaphragmatic
      muscle, prevents gastroesophageal reflux. When these structures become
      incompetent, gastric contents may cause gastroesophageal reflux disease (GERD).
      For treatment, lifestyle interventions are always recommended. We hypothesized
      that by actively training the crura of the diaphragm as part of the LES using
      breathing training exercises, GERD can be positively influenced. METHODS: A
      prospective randomized controlled study was performed. Patients with non-erosive
      GERD or healed esophagitis without large hernia and/or previous surgery were
      included. Patients were randomized and allocated either to active breathing
      training program or to a control group. Quality of life (QoL), pH-metry, and on
      demand proton pump inhibitor (PPI) usage were assessed at baseline and after 4
      weeks of training. For long-term follow-up, all patients were invited to continue
      active breathing training and were further assessed regarding QoL and PPI usage
      after 9 months. Paired and unpaired t-test was used for statistical analysis.
      RESULTS: Nineteen patients with non-erosive GERD or healed esophagitis were
      randomized into two groups (10 training group and 9 control group). There was no
      difference in baseline patient characteristics between the groups and all
      patients finished the study. There was a significant decrease in time with a
      pH<4.0 in the training group (9.1+/-1.3 vs. 4.7+/-0.9%; P<0.05), but there was no
      change in the control group. QoL scores improved significantly in the training
      group (13.4+/-1.98 before and 10.8+/-1.86 after training; P<0.01), but no changes
      in QoL were seen in the control group. At long-term follow-up at 9 months,
      patients who continued breathing exercise (11/19) showed a significant decrease
      in QoL scores and PPI usage (15.1+/-2.2 vs. 9.7+/-1.6; 98+/-34 vs. 25+/-12
      mg/week, respectively; P<0.05), whereas patients who did not train had no long
      term effect. CONCLUSIONS: We show that actively training the diaphragm by
      breathing exercise can improve GERD as assessed by pH-metry, QoL scores and PPI
      usage. This non-pharmacological lifestyle intervention could help to reduce the
      disease burden of GERD.

PMID- 22146489
TI  - IGF-1 and its receptor in esophageal cancer: association with adenocarcinoma and
      visceral obesity.
AB  - OBJECTIVES: The insulin-like growth factor (IGF) pathway and visceral obesity
      have been independently linked with esophageal cancer. This study aimed to
      delineate the differential and interlinked role of visceral obesity and the IGF-1
      system in esophageal adenocarcinoma and esophageal squamous-cell carcinoma (SCC).
      METHODS: IGF-1 receptor (IGF-1R) mRNA and protein were examined in esophageal SCC
      (KYSE 410, OE21) and esophageal adenocarcinoma (OE19, OE33) cell lines by western
      blotting. Tumor cell proliferation in response to IGF-1 was assessed by
      bromodeoxyuridine incorporation assay. In esophageal tumor sections, expression
      of IGF-1R and CD68(+) cell numbers were assessed by immunohistochemistry. IGF-1
      was measured in serum from esophageal cancer patients, Barrett's esophagus
      patients, and healthy controls by enzyme-linked immunosorbent assay. RESULTS:
      Higher IGF-1R protein expressions were observed in SCC cells compared with
      esophageal adenocarcinoma cells however only adenocarcinoma cell lines
      significantly increased proliferation in response to IGF-1 (P<0.01). Serum IGF-1
      levels were highest in esophageal adenocarcinoma patients (P<0.01) and higher in
      viscerally obese vs. nonobese (P<0.05) patients. In resected esophageal cancer,
      increased expression of IGF-1R was observed in the tumor and invasive edge
      compared with tumor-associated stroma (P<0.05), which coincided with increased
      CD68(+) cells in stromal tissue surrounding invasive tumor edge (P<0.01).
      CONCLUSIONS: This novel study examined the differential role of the IGF system in
      esophageal adenocarcinoma and SCC, and its association with visceral obesity.
      These results indicate that the IGF-1 axis has a key role in malignant
      progression of esophageal cancer, and represents a plausible mechanism through
      which visceral obesity impacts on esophageal adenocarcinoma risk and tumor
      biology.

PMID- 22146490
TI  - Evolution of quantitative methods in protein secondary structure determination
      via deep-ultraviolet resonance Raman spectroscopy.
AB  - Deep-ultraviolet resonance Raman (DUVRR) spectra is sensitive to secondary
      structural motifs but, similar to circular dichroism (CD) and infrared
      spectroscopy, requires the application of multivariate and advanced statistical
      analysis methods to resolve the pure secondary structure Raman spectra (PSSRS)
      for determination of secondary structure composition. Secondary structure motifs
      are selectively enhanced by different excitation wavelengths, a characteristic
      that inspired the first methods for quantifying secondary structures by DUVRR.
      This review traces the evolution of multivariate methods and their application to
      secondary structure composition analyses of proteins by DUVRR spectroscopy from
      the first experiments using two-wavelengths, and culminating with recent studies
      utilizing time-resolved DUVRR measurements.

PMID- 22146491
TI  - Comparative study of the efficacy and safety of two polyvalent, caprylic acid
      fractionated [IgG and F(ab')2] antivenoms, in Bothrops asper bites in Colombia.
AB  - The efficacy and safety of two polyvalent horse-derived antivenoms in Bothrops
      asper envenomings were tested in a randomized, double-blind, clinical trial
      performed in Colombia. Both antivenoms were manufactured from the same pool of
      hyperimmune plasma. Antivenom A was made of F(ab')2 fragments, generated by
      pepsin digestion and caprylic acid precipitation, whereas antivenom B consisted
      of whole IgG molecules produced by caprylic acid precipitation followed by ion
      exchange chromatography. Besides the different nature of the active substance,
      antivenom B had higher protein concentration, slightly higher turbidity and
      aggregate content. No significant differences were observed in the efficacy of
      antivenoms. Both halted local and systemic bleeding (P = 0.40) within 6-12 h of
      treatment in 100% of the cases, and restored blood coagulation (P = 0.87) within
      6-24 h in 84.7% of patients, and within 48 h in all of them, in agreement with
      restoration of plasma fibrinogen concentration. Venom concentrations in serum
      dropped significantly (P < 0.001), to very low levels, 1 h after antivenom
      infusion. Nevertheless, eight patients (11.1%), four for each antivenom,
      presented recurrence of venom antigenaemia at different times, from 6 to 96 h,
      with clinical significance (recurrent coagulopathy) only in one group B patient
      (2.9%). Serum creatine kinase (CK) activity was increased, as a consequence of
      local myonecrosis. There was no significant difference (P = 0.51) in the
      incidence of early adverse reactions to antivenom administration (28.9% for
      patients of group A and 20.6% for patients of group B), most of the reactions
      being mild, mainly cutaneous. The most frequent complications were cellulitis
      (16.7%), abscess formation (5.6%), acute renal failure (8.3%), and compartmental
      syndrome (5.6%). In conclusion, IgG and F(ab')2 antivenoms, prepared by caprylic
      acid fractionation, presented similar efficacy and safety profiles for the
      treatment of B. asper envenomings in Colombia.

PMID- 22146492
TI  - Two mutations in the C-terminal domain of influenza virus RNA polymerase PB2
      enhance transcription by enhancing cap-1 RNA binding activity.
AB  - Influenza virus RNA polymerase (RdRp) PB2 is the cap-1 binding subunit and
      determines host range and pathogenicity. The mutant human influenza virus RdRp
      containing PB2 D701N and D701N/S714R demonstrated enhanced replicon activity in
      mammalian cells. We investigated the influence of these mutations on RdRp
      activity. Cap-1-dependent transcription activities of D701N/S714R, D701N, and
      S714R were 348.1+/-6.2%, 146.4+/-11%, and 250.1+/-0.8% of that of the wild type
      (wt), respectively. Replication activity of these mutants for complimentary RNA
      to viral RNA ranged from 44% to 53% of that of the wt. Cap-1 RNA-binding
      activities of D701N/S714R, D701N, and S714R were 262+/-25%, 257+/-34%, and 315+/
      9.6% of that of the wt, respectively, and their cap-dependent endonuclease
      activities were similar to that of the wt. These mutations did not affect
      template RNA-binding activities. D701N and S714R mutations enhanced transcription
      by enhancing cap-1 RNA-binding activity, but they may exhibit decreased
      efficiency of priming by the cap-1 primer. These mutations at the C-terminal
      domain of PB2 may affect its cap-binding domain.

PMID- 22146493
TI  - Change in psychosocial distress associated with pain and functional status
      outcomes in patients with lumbar impairments referred to physical therapy
      services.
AB  - STUDY DESIGN: Prospective, longitudinal, observational cohort design. OBJECTIVE:
      The primary aim was to examine the association between changes in psychosocial
      distress (PD), and functional status (FS) and pain intensity at discharge from
      physical therapy. BACKGROUND: Patients with lumbar impairments seeking physical
      therapy commonly demonstrate elevated PD. However, it is not clear if PD changes
      that occur during physical therapy management are associated with improved
      clinical outcomes. METHODS: Data from adults (n = 692) with lumbar impairment
      were analyzed. Patients were screened using the Symptom Checklist Back Pain
      Prediction Model questionnaire (SCL BPPM) to identify patients at intake and
      discharge into 3 levels of risk for persistent disability (high, intermediate, or
      low). SCL BPPM classifications allowed for 5 patterns of change in PD during
      therapy (decreased, stable low, stable intermediate, stable high, or increased).
      Associations between PD change patterns and discharge FS and pain intensity were
      assessed using multivariable linear regression models, controlling for selected
      risk-adjustment variables. RESULTS: Proportions of patients classified by
      patterns of PD change for decreased, stable low, stable intermediate, stable
      high, and increased were 0.34, 0.52, 0.05, 0.06, and 0.03, respectively. Compared
      to the decreased PD group, (1) increased, stable high, and stable intermediate PD
      patterns were associated with worse discharge FS scores (-7.9 [95% CI: -13.5, 
      2.21], -10.9 [95% CI: -15.25, -6.49], and -8.9 [95% CI: -13.65, -4.21] units,
      respectively), and (2) stable high and stable intermediate PD patterns were
      associated with higher pain intensity (2.59 [95% CI: 1.81, 3.56] and 2.14 [95%
      CI: 1.25, 3.04] units, respectively). CONCLUSIONS: Lower FS and higher pain
      intensity outcomes were associated in similar but not identical patterns with
      patients whose SCL BPPM classification of PD increased, or remained at high or
      intermediate levels during physical therapy. Serial assessments of change in PD
      during rehabilitation are recommended as a possible treatment-monitoring tool.

PMID- 22146494
TI  - CT stress myocardial perfusion imaging using multidetector CT--A review.
AB  - Computed tomography coronary angiography (CTA) accurately detects and excludes
      coronary artery disease (CAD); however, the physiological significance of
      coronary artery lesions may be uncertain. CT myocardial perfusion imaging (CTP)
      acquired during vasodilator stress provides a novel and emerging method for
      detection of myocardial ischemia. Multiple studies have established the
      feasibility of CTP and suggested its incremental value when used in combination
      with CTA in the identification of hemodynamically significant stenoses as
      compared with CTA alone. Despite these encouraging clinical data, CT perfusion
      assessment is in its infancy, as further research is required to validate and
      optimize this new technique. Combined CTA/CTP imaging has significant potential,
      as it offers the convenience of assessing both coronary anatomy and myocardial
      perfusion in one single examination at a radiation dose equivalent to
      contemporary nuclear medicine imaging. In this review, we provide an overview of
      the fundamentals of CT perfusion imaging, recent advances in scanner types and
      imaging techniques and protocols, and current literature on the accuracy of CTP,
      concluding with its future challenges and directions.

PMID- 22146495
TI  - A stepwise approach to the visual interpretation of CT-based myocardial
      perfusion.
AB  - Cardiovascular anatomic and functional testing have been longstanding and key
      components of cardiac risk assessment. As part of that strategy, CT-based imaging
      has made steady progress, with coronary computed tomography angiography (CTA) now
      established as the most sensitive noninvasive strategy for assessment of
      significant coronary artery disease. Myocardial CT perfusion imaging (CTP), as
      the functional equivalent of coronary CTA, is being tested in currently ongoing
      multicenter trials and is proposed to enhance the accuracy of coronary CTA alone.
      However, unlike coronary CTA that has published guidelines for interpretation and
      is rapidly gaining applicability in the noninvasive risk assessment paradigms,
      myocardial CTP is rapidly evolving, and guidance on a standard approach to its
      interpretation is lacking. In this article we describe a practical stepwise
      approach for interpretation of myocardial CTP that should add to the clinical
      applicability of this modality. These steps include (1) coronary CTA
      interpretation for potentially obstructive atherosclerosis, (2) reconstruction
      and preprocessing of myocardial CTP images, (3) image quality assessment and the
      identification of potentially confounding artifacts, (4) rest and stress image
      interpretation for enhancement patterns and areas of hypoattenuation, and (5)
      correlation of coronary anatomy and myocardial perfusion deficits. This
      systematic review uses already published methods from multiple clinical studies
      and is intended for general usage, independent of the platform used for image
      acquisition.

PMID- 22146497
TI  - Incremental value of myocardial perfusion over regional left ventricular function
      and coronary stenosis by cardiac CT for the detection of acute coronary syndromes
      in high-risk patients: a subgroup analysis of the ROMICAT trial.
AB  - OBJECTIVES: To determine the incremental benefit of assessing myocardial
      perfusion defects (MPD) for acute coronary syndromes (ACS) over coronary and
      functional assessment by rest cardiac computed tomography (CT) in patients with
      acute chest pain. BACKGROUND: Assessment of myocardial perfusion is feasible with
      cardiac CT; however, the diagnostic value of this assessment in patients at risk
      for ACS has not been demonstrated. METHODS: The study included patients who
      presented to the emergency department with acute chest pain, nonischemic initial
      electrocardiogram (ECG), and negative cardiac biomarkers but had clinical
      suspicion for ACS and underwent invasive coronary angiography (ICA). Results were
      blinded to caregivers and patients. CT data sets were independently assessed for
      the presence of coronary plaque and stenosis, regional left ventricular function,
      and myocardial perfusion deficits by 2 blinded observers. Coronary angiography
      was assessed for the presence of stenosis, TIMI myocardial perfusion grade, and
      corrected TIMI frame count. The endpoint was ACS during index hospitalization.
      RESULTS: We analyzed data from 35 subjects (69% male, mean age 58 +/- 9 years) of
      whom 22 (63%) had ACS. The sensitivity and specificity of MPD for ACS were 86%
      (95% CI: 64%-96%) and 62% (95% CI: 32%-85%), respectively. Combined, MPD and RWMA
      assessment resulted in specificity and sensitivity of 86% (95% CI: 64%-96%) and
      85% (95% CI: 54%-97%), respectively. Adding MPD and RWMA to the assessment for
      significant stenosis (>50%) resulted in a higher sensitivity of 91% (69-98%) and
      specificity of 85% (54-97%) and a significantly increased overall diagnostic
      accuracy when compared with assessment for stenosis (AUC: 0.88 vs 0.79;
      respectively, P = 0.02). Diagnostic accuracy of CT was not associated with
      impaired CTFC >40 or myocardial TIMI perfusion grade < 3. CONCLUSIONS: Assessment
      of myocardial perfusion and regional wall motion abnormalities may enhance the
      ability of CT to detect ACS in patients with acute chest pain.

PMID- 22146496
TI  - Diagnostic performance of combined noninvasive coronary angiography and
      myocardial perfusion imaging using 320 row detector computed tomography: design
      and implementation of the CORE320 multicenter, multinational diagnostic study.
AB  - Multidetector coronary computed tomography angiography (CTA) is a promising
      modality for widespread clinical application because of its noninvasive nature
      and high diagnostic accuracy as found in previous studies using 64 to 320
      simultaneous detector rows. It is, however, limited in its ability to detect
      myocardial ischemia. In this article, we describe the design of the CORE320 study
      ("Combined coronary atherosclerosis and myocardial perfusion evaluation using 320
      detector row computed tomography"). This prospective, multicenter, multinational
      study is unique in that it is designed to assess the diagnostic performance of
      combined 320-row CTA and myocardial CT perfusion imaging (CTP) in comparison with
      the combination of invasive coronary angiography and single-photon emission
      computed tomography myocardial perfusion imaging (SPECT-MPI). The trial is being
      performed at 16 medical centers located in 8 countries worldwide. CT has the
      potential to assess both anatomy and physiology in a single imaging session. The
      co-primary aim of the CORE320 study is to define the per-patient diagnostic
      accuracy of the combination of coronary CTA and myocardial CTP to detect
      physiologically significant coronary artery disease compared with (1) the
      combination of conventional coronary angiography and SPECT-MPI and (2)
      conventional coronary angiography alone. If successful, the technology could
      revolutionize the management of patients with symptomatic CAD.

PMID- 22146498
TI  - Incremental value of an integrated adenosine stress-rest MDCT perfusion protocol
      for detection of obstructive coronary artery disease.
AB  - BACKGROUND: Preliminary studies have shown the potential of myocardial computed
      tomography perfusion (CTP) analysis for ischemia detection in both animals and
      humans. OBJECTIVE: To provide validation data on stress-rest CTP protocols as
      additive tools to improve the accuracy of multidetector computed tomography
      (MDCT) for coronary artery disease (CAD) in symptomatic patients. METHODS: Ninety
      symptomatic patients with suspected CAD (62 +/- 8 years, 66% males) underwent
      both MDCT and invasive coronary angiography (XA). The MDCT protocol included a
      prospective calcium score acquisition, a helical acquisition with retrospective
      gating during infusion of adenosine (140 MUg/kg/min) and a prospective scan for
      computed tomography angiography (CTA) at rest (total effective radiation dose:
      5.1 +/- 0.8 mSv). Significant and higher-grade CADs were defined by the presence
      of >=50% or >=70% stenosis in at least one coronary artery, as evaluated by
      quantitative coronary angiography (QCA) using XA images. RESULTS: On a patient
      based model, CTA sensitivity, specificity, and positive (PPV) and negative
      predictive values (NPV) to detect >=50% or >=70% stenosis were 98%, 71%, 80%, and
      97% (global accuracy 86%) and 100%, 60%, 64%, and 100% (accuracy 77%),
      respectively. An integrative approach of CTA and CTP results had the best
      performance for detection of CAD with sensitivity of 83%, specificity of 98%, PPV
      of 98%, and NPV of 84% (accuracy 84%) for detection of 50% stenosis and 97%, 90%,
      88%, and 98% (accuracy 93%), respectively, for the 70% threshold. The integration
      of results had the best overall performance in all scenarios but was particularly
      advantageous in the prediction of higher-grade CAD, with an area under the curve
      of 0.93, compared with 0.80 for isolated CTA and 0.82 for CTP and in patients
      with severe calcifications (sensitivity 92%, specificity 87%, overall accuracy of
      90%). CONCLUSIONS: The integration of functional and morphological data using CTA
      and CTP improved MDCT accuracy for detection of clinically relevant CAD at both
      thresholds of 50% and 70% in this intermediate to high pretest probability
      population.

PMID- 22146499
TI  - Normal perfusion of the left ventricular myocardium using 320 MDCT.
AB  - BACKGROUND: CT myocardial perfusion imaging is an emerging CT application using
      density measurements of contrast-enhanced left ventricular (LV) myocardium.
      OBJECTIVE: Using a 320-MDCT we have consistently observed lower Hounsfield unit
      (HU) values in the lateral LV myocardium, potentially mimicking perfusion
      defects. This study aimed to evaluate contrast-enhancement patterns of the LV
      myocardium in normal studies. METHODS: Twenty-one clinical cases with normal
      coronary MDCT-based angiography findings, as determined by 2 qualified readers,
      were selected for retrospective evaluation. Using 8 identically sized and
      positioned ROIs, the HU measurements were recorded from short axis axial
      reconstructions through the LV myocardium in middle, apical, and basal locations.
      Scans were acquired on a 320-slice MDCT unit. RESULTS: The middle short axis
      location demonstrated HU densities of 79.4 (range 42.3-162.7) in the lateral
      myocardial wall (regions 2, 3, and 4) compared with 103.9 (range 11.4-159.6) in
      the inferior, septal, and anterior walls (regions 1, 5, 6, 7, and 8; P < 0.001).
      HU densities for the basal slice were 82.3 (range 51.5-168.4) in the lateral wall
      compared with 94.9 (range 35.3-144) in the inferior, septal, and anterior walls
      (P < 0.001). In the apical location, HU densities were 79.9 (range 42.3-139.3) in
      the lateral wall compared with 100.9 (range 69.0-170.5) in the inferior, septal,
      and anterior walls (P < 0.001). CONCLUSION: Normal LV myocardial enhancement
      using a 320-slice MDCT demonstrates significantly lower densities in the lateral
      wall when compared with the anterior, septal, and inferior walls in patients with
      normal coronary vascular anatomy. Assessment of CT myocardial perfusion studies
      should therefore be undertaken with caution, to prevent misrepresenting these
      lower-density values in the LV lateral wall.

PMID- 22146500
TI  - Myocardial hypo-enhancement on resting computed tomography angiography images
      accurately identifies myocardial hypoperfusion.
AB  - OBJECTIVE: The objective of this study was to test the diagnostic accuracy of
      myocardial CT perfusion (CTP) imaging using color and gray-scale image analysis.
      BACKGROUND: Current myocardial CTP techniques have varying diagnostic accuracy
      and are prone to artifacts that impair detection. This study evaluated the
      diagnostic accuracy of color and/or gray-scale CTP and the application of
      artifact criteria to detect hypoperfusion. METHODS: Fifty-nine prospectively
      enrolled patients with abnormal single-photon emission computed tomography
      (SPECT) studies were analyzed. True hypoperfusion was defined if SPECT
      hypoperfusion corresponded to obstructive coronary stenoses on CT angiography
      (CTA). CTP applied color and gray-scale myocardial perfusion maps to resting CTA
      images. Criteria for identifying artifacts were also applied during
      interpretation. RESULTS: Using combined SPECT plus CTA as the diagnostic
      standard, abnormal myocardial CTP was present in 33 (56%) patients, 19 suggesting
      infarction and 14 suggesting ischemia. Patient-level color and gray-scale
      myocardial CTP sensitivity to detect infarction was 90%, with specificity 80%,
      and negative and positive predictive value of 94% and 68%. To detect ischemia or
      infarction, CTP specificity and positive predictive value were 92% whereas
      sensitivity was 70%. Gray-scale myocardial CTP had slightly lower specificity but
      similar sensitivity. Myocardial CTP artifacts were present in 88% of studies and
      were identified using our criteria. CONCLUSIONS: Color and gray-scale myocardial
      CTP using resting CTA images identified myocardial infarction with high
      sensitivity as well as infarction or ischemia with high specificity and positive
      predictive value without additional testing or radiation. Color and gray-scale
      CTP had slightly better specificity than gray-scale alone.

PMID- 22146501
TI  - CT detection of myocardial blood volume deficits: dual-energy CT compared with
      single-energy CT spectra.
AB  - BACKGROUND: The performance of dual-energy CT (DECT) for the detection of
      myocardial blood volume deficits has not systematically been compared with single
      energy CT (SCT) spectra. OBJECTIVE: We evaluated the accuracy for detection of
      myocardial blood volume deficits in DECT and SCT compared with 99m-Tc-Sestamibi
      SPECT (single-photon emission CT) during rest and stress. METHODS: 47 patients
      underwent rest/stress SPECT myocardial perfusion imaging and cardiac DECT on a
      dual-source CT scanner. The A- and B-tubes were operated with 140 kV and 80
      kV/100 kV, respectively. DECT raw data were reconstructed by (1) only using high
      energy (140 kV) CT spectra, (2) only using low-energy (80 kV/100 kV) CT spectra,
      (3) merging data (30% low- and 70% high-energy CT spectra), and (4) DECT-based
      iodine maps. Two independent, blinded observers analyzed all CT data according to
      each of the 4 reconstruction strategies for myocardial blood volume deficits.
      RESULTS: Specificity and positive predictive values were relatively similar
      between the 4 reconstruction strategies, with highest specificity (98%) of SCT
      datasets based on 140 kV for mixed perfusion deficits seen on SPECT. DECT iodine
      maps showed highest sensitivity, negative predictive value, and accuracy of 91%,
      97%, and 93%, respectively, for mixed perfusion deficits. Analysis with receiver
      operating characteristics showed highest area under the curve values (0.84-0.93)
      with the use of DECT iodine maps in the detection of purely fixed and mixed
      perfusion deficits. CONCLUSION: DECT iodine maps show superior performance for
      the detection of fixed and mixed perfusion deficits compared with SCT spectra.

PMID- 22146502
TI  - Quantitative myocardial perfusion imaging using rapid kVp switch dual-energy CT:
      preliminary experience.
AB  - BACKGROUND: Quantitative myocardial CT perfusion (CTP) is susceptible to beam
      hardening (BH) artifact from conventional single-energy (kVp) CT (SECT) scanning,
      which can mimic perfusion deficits. OBJECTIVE: We evaluated the minimization of
      BH artifact with dual-energy (kVp) CT (DECT) generated monochromatic CT images to
      improve perfusion estimates. METHODS: We investigated the performance of DECT
      with a scanner capable of rapid kVp switching with respect to (1) BH artifact in
      a myocardium phantom model comparing SECT with image-based DECT and projection
      based DECT, (2) optimal imaging parameters for measuring iodine concentration at
      high contrast-to-noise ratio in a tissue characterization phantom model, and (3)
      the feasibility of a dynamic time-resolved scan protocol with the projection
      based DECT technique to measure myocardial perfusion in normal (nonischemic)
      porcine. RESULTS: In a myocardium phantom model, projection-based DECT 70 keV was
      better able to minimize the difference in the attenuation of the myocardium (19.9
      HU) between having and not having contrast in the heart chambers in comparison to
      SECT using 80 kVp (30.4 HU) or 140 kVp ( 23.3 HU) and image-based DECT 70 keV
      (27.5 HU). Further, projection-based DECT 70 keV achieved the highest contrast-to
      noise ratio (3.0), which exceeded that from imaged-based DECT 70 keV (2.0), 140
      kVp SECT (1.3), and 80 kVp SECT (2.9). In 5 normal pigs, projection-based DECT at
      70 keV provided a more uniform perfusion estimate than SECT. CONCLUSION: By
      effectively reducing BH artifact, projection-based DECT may permit improved
      quantitative myocardial CTP compared with the conventional SECT technique.

PMID- 22146503
TI  - Dipyridamole stress and rest transmural myocardial perfusion ratio evaluation by
      64 detector-row computed tomography.
AB  - BACKGROUND: Myocardial stress CT perfusion (CTP) can detect myocardial ischemia.
      OBJECTIVE: We evaluated the transmural perfusion ratio (TPR) of dipyridamole
      stress CTP to detect significant coronary stenosis (>70%) defined by quantitative
      invasive coronary angiography (ICA). METHODS: Twenty-six patients (61.6 +/- 8.0
      years old; 14 males), without prior myocardial infarction, with positive single
      photon emission computed tomography (SPECT; <2 months) and clinical indication
      for ICA, underwent a customized multidetector-row CT (MDCT) protocol with
      rest/stress myocardial perfusion evaluation and coronary CT angiography. TPR was
      defined as mean subendocardial divided by mean subepicardial attenuation and
      quantified on rest and stress MDCT images. Abnormal TPR was defined as 2 SDs
      below the mean rest TPR. RESULTS: All 26 patients completed the CT protocol with
      no adverse events. Rest TPR was measured in all patients with a mean of 1.06 +/-
      0.11, and abnormal TPR was considered <0.85. For 6 patients with normal coronary
      arteries by ICA, the mean TPR of territories with a previous positive perfusion
      defect in SPECT was 1.02 +/- 0.18 (95% CI, 0.86-1.18; n = 6), and mean TPR of
      territories without perfusion defect in SPECT was 1.03 +/- 0.09 (95% CI, -0.95 to
      1.11; n = 12; P = 0.83). Mean stress TPR in territories with positive SPECT and
      significant coronary artery disease by quantitative ICA was 0.71 +/- 0.13 (95%
      CI, -0.64 to 0.77) and in the remote myocardial was 1.01 +/- 0.09 (95% CI, -0.96
      to 1.06; P < 0001). In these territories, a significant Pearson's correlation was
      observed (r = -0.74, P < 0.001). CONCLUSION: TPR has a good correlation with
      SPECT and ICA to detect significant coronary stenosis.

PMID- 22146504
TI  - Additional value of dipyridamole stress myocardial perfusion by 64-row computed
      tomography in patients with coronary stents.
AB  - BACKGROUND: Coronary computed tomography angiography (CTA) is a well-established
      diagnostic tool for coronary artery disease (CAD). However, coronary segments
      with prior stent implantation visualized with CTA may have limited evaluation and
      reduced accuracy. OBJECTIVE: We assessed the incremental value of stress
      myocardial CT perfusion (CTP) over anatomical assessment by coronary CTA alone in
      patients with stents, using quantitative invasive coronary angiography (>=50%) as
      reference. METHODS: Forty-six patients (56.9 +/- 7.2 years; 28 men) referred to
      invasive coronary angiography were evaluated, combining coronary CTA and
      dipyridamole stress myocardial CTP with 64 detector-row CT. Coronary CTA was
      evaluated for >=50% coronary stenosis, and myocardial CTP was used to potentially
      reclassify coronary territories, including those with stents and poorly evaluated
      stents because of artifacts. RESULTS: We evaluated 138 coronary territories, 62
      with >=1 stent. From these, 21 (34%) territories had adequately evaluated stents,
      28 (45%) had limitedly evaluated stents still allowing diagnosis, and 13 (21%)
      had inadequately evaluated stents (no luminal assessment possible). Sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy
      for coronary CTA in stent territories were, respectively, 85%, 77%, 87%, 74%, and
      81%, and the combined use of coronary CTA and myocardial CTP were 88%, 95%, 97%,
      81%, and 91% (P = 0.0292). In territories with impaired stent evaluation (limited
      or inadequate), the diagnostic performance of coronary CTA alone was 83%, 72%,
      79%, 76% and 77%, and combined with myocardial CTP were 87%, 94%, 95%, 85%, and
      91% (P = 0.036). CONCLUSION: The combined evaluation of coronary CTA and stress
      myocardial CTP improved the diagnostic accuracy for the detection of significant
      obstructive CAD in patients with stents.

PMID- 22146505
TI  - A comparison of reconstruction and viewing parameters on image quality and
      accuracy of stress myocardial CT perfusion.
AB  - BACKGROUND: Myocardial stress computed tomography perfusion (CTP) has similar
      diagnostic accuracy for detecting perfusion defects (PDs) versus single-photon
      emission computed tomography (SPECT). However, the optimal diagnostic viewing and
      image processing parameters for CTP are unknown. OBJECTIVE: We sought to compare
      the diagnostic accuracy of different image processing techniques, cardiac phases,
      slice thicknesses, and viewing parameters for detection of PDs. METHODS: A stress
      and rest dual-source CTP protocol was performed with adenosine. Twelve subjects
      with severe stenosis proven by quantitative coronary angiography (QCA), with
      corresponding territorial defects at SPECT, were selected as well as 7 controls
      (subjects with similar clinical suspicion but negative QCA and SPECT). Short-axis
      stress images were processed with 3 techniques: minimum intensity projection
      (MinIP), maximum intensity projection, and average intensity multiplanar
      reconstruction (MPR), 3 thicknesses (1, 3, 8 mm), and 2 phases (systolic, mid
      diastolic). The resulting images (n = 1026) were randomized and interpreted by
      independent readers. RESULTS: Diastolic reconstructions (8-mm MPR) showed the
      highest sensitivity (81%) to detect true PDs. The highest accuracy was achieved
      with the 8-mm (61%) and 1-mm (61%) MPR diastolic images. The most sensitive and
      accurate systolic reconstructions were 3-mm MinIP images. These findings related
      to viewing in relatively narrow window width and window level settings.
      CONCLUSION: Viewing parameters for optimal accuracy in detection of perfusion
      defects on CTP differ for systolic and diastolic images.

PMID- 22146506
TI  - Quantitative myocardial CT perfusion: a pictorial review and the current state of
      technology development.
AB  - Coronary artery disease (CAD) is one of the leading causes of morbidity and
      mortality, and is associated with substantial and increasing resource burden. A
      combined physiologic and anatomic assessment may improve identification of
      patients with CAD who would benefit from revascularization and reduce unnecessary
      diagnostic and interventional procedures. Cardiovascular computed tomography (CT)
      has the potential to provide a comprehensive evaluation of CAD in a single
      setting. Although coronary CT angiography has been widely implemented for
      clinical use, the application of myocardial CT perfusion (CTP) has been
      relatively restricted because of a few limitations, such as beam hardening and
      the high radiation dose delivered. In this article, we first review the
      fundamental basis of the qualitative, semiquantitative, and quantitative
      techniques for myocardial CTP and discussed the strength and weakness of each
      approach. Beam-hardening correction for myocardial CTP with image-based method
      and dual-energy CT are then discussed with example cases demonstrating the
      effectiveness of each method. Initial experiences suggest both techniques can
      reduce beam-hardening artifact to a satisfactory extent. An overview on dose
      reduction technologies, such as prospective ECG triggering and iterative
      reconstruction for myocardial CTP, is also provided. Preclinical studies suggest
      it is feasible to perform low-dose quantitative myocardial CTP without affecting
      perfusion measurement. Finally, the impact of scan length on myocardial CTP is
      addressed.

PMID- 22146507
TI  - Paying it forward.

PMID- 22146508
TI  - Reactive oxygen species and angiotensin II response in human omental arteries:
      what about tachyphylaxis?

PMID- 22146509
TI  - Contribution of circulating angiotensinogen concentrations to variations in
      aldosterone and blood pressure in a group of African ancestry depends on salt
      intake.
AB  - In high-Na(+), low-K(+) diets, which suppress renin release in salt-sensitive
      groups, the mechanisms maintaining increases in renin-angiotensin-aldosterone
      system activation downstream from renin and renin-angiotensin-aldosterone system
      induced effects on blood pressure (BP) are uncertain. Whether circulating
      angiotensinogen concentrations (AGT) or its determinants may contribute to
      maintaining serum aldosterone concentrations (aldosterone) and increases in BP on
      high-Na(+), low-K(+) diets was evaluated in 579 participants of a community
      sample of African ancestry. Plasma renin concentrations were inversely related to
      BP (P<0.0001) and an index of salt intake (24-hour urinary Na(+)/K(+), P<0.0001).
      An interaction between AGT and urinary Na(+)/K(+) was independently associated
      with aldosterone (P<0.001) and systolic BP (SBP; P<0.05). Independent of
      confounders, in participants with urinary Na(+)/K(+) at or more than the median
      for the sample, AGT was positively associated with aldosterone (P<0.0001) and SBP
      (P<0.005). No independent AGT-aldosterone or AGT-SBP relationships were noted in
      participants with urinary Na(+)/K(+) less than the median for the sample.
      Standardized beta-coefficients (slopes) of AGT-aldosterone and AGT-SBP
      relationships were greater in participants with urinary Na(+)/K(+) at or more
      than the median (AGT-aldosterone=0.30+/-0.06, AGT-SBP=0.16+/-0.05) compared with
      those with urinary Na(+)/K(+) less than the median (AGT-aldosterone=-0.04+/-0.06;
      AGT-SBP=-0.03+/-0.05; P<0.01-0.0001 for comparison of slopes). The AGT-SBP
      relationship in participants with urinary Na(+)/K(+) at or more than the median
      for the sample was equivalent to the relationship between body mass index and BP.
      In conclusion, in participants of African ancestry, in the presence of high
      Na(+), low-K(+) diets, which suppress renin release, renin-angiotensin
      aldosterone system activation and its impact on BP are maintained in part by AGT.

PMID- 22146510
TI  - (23)Na magnetic resonance imaging of tissue sodium.
AB  - Hypertension is linked to disturbed total-body sodium (Na(+)) regulation;
      however, measuring Na(+) disposition in the body is difficult. We implemented
      (23)Na magnetic resonance spectroscopy ((23)Na-MR) and imaging technique ((23)Na
      MRI) at 9.4T for animals and 3T for humans to quantify Na(+) content in skeletal
      muscle and skin. We compared (23)Na-MRI data with actual tissue Na(+) content
      measured by chemical analysis in animal and human tissue. We then quantified
      tissue Na(+) content in normal humans and in patients with primary aldosteronism.
      We found a 29% increase in muscle Na(+) content in patients with aldosteronism
      compared with normal women and men. This tissue Na(+) was mobilized after
      successful treatment without accompanying weight loss. We suggest that, after
      further refinements, this tool could facilitate understanding the relationships
      between Na(+) accumulation and hypertension. Furthermore, with additional
      technical advances, a future clinical use may be possible.

PMID- 22146511
TI  - Fish, n-3 fatty acids, and cardiovascular diseases in women of reproductive age:
      a prospective study in a large national cohort.
AB  - Previous studies have indicated a protective effect of long-chain n-3
      polyunsaturated fatty acids (LCn3FAs) against cardiovascular disease; however,
      women are underrepresented in cardiovascular research. The aim of this study was
      to explore the association between intake of LCn3FAs and the risk of
      cardiovascular disease in a large prospective cohort of young women (mean age at
      baseline: 29.9 years [range: 15.7-46.9]). Exposure information on 48 627 women
      from the Danish National Birth Cohort was linked to the Danish National Patients
      Registry for information on events of hypertensive, cerebrovascular, and ischemic
      heart disease used to define a combined measure of cardiovascular diseases.
      Intake of fish and LCn3FAs was assessed by a food-frequency questionnaire and
      telephone interviews. During follow-up (1996-2008; median: 8 years), 577 events
      of cardiovascular disease were identified. Low LCn3FA intake was associated with
      an increased risk of cardiovascular disease (adjusted hazard ratio for women in
      lowest versus highest LCn3FA intake group: 1.91 [95% CI: 1.26-2.90]). Restricting
      the sample to women who had consistently reported similar frequencies of fish
      intake across 3 different dietary assessment occasions tended to strengthen the
      relationship (hazard ratio for lowest versus highest intake: 2.91 [95% CI: 1.45
      5.85]). Furthermore, the observed associations were consistent in supplementary
      analyses where LCn3FA intake was averaged across the 3 dietary assessment
      occasions, and the associations were persistent for all 3 of the individual
      outcomes. Our findings based on a large prospective cohort of relatively young
      and initially healthy women indicated that little or no intake of fish and
      LCn3FAs was associated with an increased risk of cardiovascular disease.

PMID- 22146512
TI  - T regulatory lymphocytes prevent aldosterone-induced vascular injury.
AB  - Aldosterone mediates actions of the renin-angiotensin-aldosterone system inducing
      hypertension, oxidative stress, and vascular inflammation. Recently, we showed
      that angiotensin II-induced hypertension and vascular damage are mediated at
      least in part by macrophages and T-helper effector lymphocytes. Adoptive transfer
      of suppressor T-regulatory lymphocytes (Tregs) prevented angiotensin II action.
      We hypothesized that Treg adoptive transfer would blunt aldosterone-induced
      hypertension and vascular damage. Thirteen to 15-week-old male C57BL/6 mice were
      injected intravenously at 1-week intervals with 3*10(5) CD4(+)CD25(+) cells
      (representing Treg) or control CD4(+)CD25(-) cells and then infused or not for 14
      days with aldosterone (600 MUg/kg per day, SC) while receiving 1% saline to
      drink. Aldosterone induced a small but sustained increase in blood pressure
      (P<0.001), decreased vasodilatory responses to acetylcholine by 66% (P<0.001),
      increased both media:lumen ratio (P<0.001) and media cross-sectional area of
      resistance arteries by 60% (P<0.05), and increased NADPH oxidase activity 2-fold
      in aorta (P<0.001), kidney and heart (P<0.05), and aortic superoxide production.
      As well, aldosterone enhanced aortic and renal cortex macrophage infiltration and
      aortic T-cell infiltration (all P<0.05), and tended to decrease Treg in the renal
      cortex. Treg adoptive transfer prevented all of the vascular and renal effects
      induced by aldosterone. Adoptive transfer of CD4(+)CD25(-) cells exacerbated
      aldosterone effects except endothelial dysfunction and increases in media:lumen
      ratio of resistance arteries. Thus, Tregs suppress aldosterone-mediated vascular
      injury, in part through effects on innate and adaptive immunity, suggesting that
      aldosterone-induced vascular damage could be prevented by an immunomodulatory
      approach.

PMID- 22146513
TI  - Unraveling the mechanism of renin-angiotensin- aldosterone system activation and
      target organ damage in hypertensive blacks.

PMID- 22146514
TI  - Eplerenone use in primary aldosteronism during pregnancy.

PMID- 22146515
TI  - Pyroelectric properties of an antiferroelectric liquid crystal.
AB  - The effects of temperature and applied voltage on the pyroelectric properties of
      an antiferroelectric liquid crystal are given. It has been found that the
      pyroelectric signal depends strongly on the bias voltage across the sample. The
      pyroelectric signal behaviour is interpreted with the aid of spontaneous
      polarization data and good agreement is found between the results from the
      pyroelectric and polarization techniques. The spontaneous polarization of the
      sample exhibits the temperature- and field-induced 'Devil's staircase' behaviour,
      as predicted by the Ising model.

PMID- 22146516
TI  - Visual sequelae after consensus-based treatment of ophthalmic artery segment
      aneurysms: the Johns Hopkins experience.
AB  - BACKGROUND: To determine the anatomic and visual outcomes of patients with
      ophthalmic artery segment aneurysms treated at The Johns Hopkins Hospital using a
      consensus-based treatment algorithm. METHODS: Retrospective record review of a
      prospectively accrued case series of 88 patients (101 aneurysms) treated between
      January 2004 and July 2009. Presenting symptoms and aneurysm parameters were
      recorded for all subjects. Treatment strategy for all patients was determined by
      consensus among neurosurgeons, neurointerventionalists, neurologists, and
      neuroophthalmologists meeting to review the clinical cases on a weekly basis.
      Final clinical outcomes (aneurysm control, functional status, and vision) were
      ascertained from in-house examinations, medical records, telephone interviews, or
      a combination of these methods. Risk factors for visual or other complications
      were evaluated. RESULTS: An optic neuropathy was present in at least 30 (34%) of
      88 patients after treatment. Presumed new visual loss occurred in 24 (27%) of
      these patients. The remaining 6 patients had preexisting optic neuropathy-related
      visual loss that worsened after treatment. No patient with a preexisting optic
      neuropathy improved following treatment. CONCLUSION: Ophthalmic artery segment
      aneurysms present a treatment challenge because of their anatomic complexity and
      relationship to critical neural structures, particularly the visual sensory
      pathway. We have adopted a consensus-based treatment approach in an effort to
      optimize patient outcomes and aneurysm control. Although our approach resulted in
      durable treatment of the aneurysm, a sizable proportion of patients experienced
      new vision loss after treatment, and no patient with preexisting visual loss
      related to their aneurysm experienced visual improvement after treatment. We
      recommend that all patients with ophthalmic artery aneurysms receive careful and
      thorough preprocedural counseling to ensure they are aware of the risks and
      benefits of treatment regardless of the method used.

PMID- 22146517
TI  - Tributes to Jean Thivolet (1926-2011).

PMID- 22146519
TI  - Final-state effects in neutron Compton scattering measurements on zirconium
      deuteride and beryllium.
AB  - We report inelastic neutron scattering measurements of the neutron Compton
      profile, J(y), for Be and for D in polycrystalline [Formula: see text] over a
      range of momentum transfers,  q between 27 and [Formula: see text]. The
      measurements were performed using the inverse geometry spectrometer eVS which is
      situated at the UK pulsed spallation neutron source ISIS. We have investigated
      deviations from impulse approximation (IA) scattering which are generically
      referred to as final-state effects (FSEs) using a method described by Sears. This
      method allows both the magnitude and the  q dependence of the FSE to be studied.
      Analysis of the measured data was compared with analysis of numerical simulations
      based on the harmonic approximation and good agreement was found for both
      [Formula: see text] and Be. Finally we have shown how [Formula: see text], where
      V is the interatomic potential, can be extracted from the antisymmetric component
      of J(y).

PMID- 22146520
TI  - Contribution of pelvic and para-aortic lymphadenectomy with sentinel node biopsy
      in patients with IB2-IIB cervical cancer.
AB  - OBJECTIVE: Detection of lymph node involvement in women with IB2-IIB cervical
      cancer could have a positive effect on survival. We set out to evaluate the
      incidence of pelvic and/or para-aortic lymph node involvement using the sentinel
      node (SN) biopsy and its impact on survival. METHODS: From 2002 to 2010, 66 women
      with IB2-IIB cervical cancer underwent a pelvic and paraaortic lymphadenectomy
      with SN biopsy. Survival between groups according to lymph node status was
      evaluated. RESULTS: Mean tumour size was 43.5 mm. At least one SN was detected in
      69% of the 45 SN procedures performed. Sixteen of these patients had metastatic
      SN and the false negative rate was 20%. Metastatic pelvic SNs or non-SNs were
      detected in 33 patients (50%), including pelvic-positive nodes in 26 (40%),
      pelvic- and paraaortic-positive lymph nodes in seven (11%), and paraaortic skip
      metastases in two (6%). Positive paraaortic node was the sole determinant for
      disease-free survival (DFS) and overall survival (OS; P<0.001). Differences in
      DFS and OS between groups according to the nodal status were observed (P<0.001).
      CONCLUSION: SN procedure gave a higher rate of metastasis detection. Further
      studies are required to evaluate whether pre-therapeutic node staging, including
      paraaortic and pelvic lymphanedectomy, should be performed.

PMID- 22146521
TI  - The proline TP53 variant stimulates likely lymphangiogenesis in an orthotopic
      mouse model of pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is a deadly disease characterised by high incidence
      of TP53 mutations. Restoration of TP53 function is perceived as a highly
      attractive therapeutic strategy, whose effects are not well characterised.
      METHODS: The current work adapted an inducible strategy of stage-specific
      reexpression of wild-type (wt) TP53 in an in vivo orthotopic mouse model of
      pancreatic cancer. RESULTS: The reconstitution of wt TP53 function in TP53-mutant
      DanG and MiaPaCa-2 cells caused G1 cell cycle arrest but no evidence of apoptosis
      induction. Consistent with subcutaneous xenograft models, we found that wt TP53
      reduced primary tumour growth. Wt TP53 reexpression during early tumour growth
      led to significant increase in vascularisation. This correlated with an
      unexpectedly high rate of micro-metastases in lymph nodes of animals with wt TP53
      induction, despite the 90% decrease in median primary tumour weight. Reexpression
      of wt TP53 later in tumour development did not significantly affect the number of
      CD31-reactive vessels, but increased lymphatic vessel density. CONCLUSION: The
      increased number of lymphatic vessels and micro-metastases suggests that wt TP53
      induction complexly affected the biology of different tumour constituents of
      pancreatic cancer. Our observation suggests that combination of the inducible
      system with an orthotopic model can yield important insights into in vivo
      pancreatic cancer biology.

PMID- 22146522
TI  - Severe reaction to radiotherapy for breast cancer as the presenting feature of
      ataxia telangiectasia.
AB  - BACKGROUND: Severe early and late radiation reaction to radiotherapy is extremely
      rare in breast cancer patients. Such a reaction prompted an investigation into a
      44-year-old mother (patient A-T213). METHODS: A neurological examination was
      performed and blood lymphocytes and skin fibroblasts were assessed for
      radiosensitivity chromosomally and by colony-forming assay. The ATM gene was
      sequenced and ATM mutations modelled by site-directed mutagenesis. The ATM kinase
      activity was also assessed. RESULTS: Patient A-T213 was normally ambulant with no
      ataxia and minimal other neurological features. T lymphocytes and skin
      fibroblasts were unusually radiosensitive, although less sensitive than in
      classical ataxia telangiectasia (A-T). A lymphoblastoid cell line and skin
      fibroblasts expressed ATM protein with some retained kinase activity. One
      missense ATM mutation c.8672G>A (p.Gly2891Asp) and a c.1A>G substitution were
      identified. In the modelling system, the p.Gly2891Asp mutant protein was
      expressed and shown to have residual ATM kinase activity. CONCLUSION: Patient A
      T213 has a milder form of A-T with biallelic ATM mutations, which may have
      contributed to breast cancer development, and certainly caused the severe
      radiation reaction. Ataxia telangiectasia should be investigated as a potential
      cause of untoward severe early and late radiation reactions in breast cancer
      patients.

PMID- 22146523
TI  - Benefit of chemotherapy as part of treatment for HPV DNA-positive but p16
      negative squamous cell carcinoma of the oropharynx.
AB  - BACKGROUND: To determine (a) the cause of an improvement in survival from
      oropharyngeal squamous cell carcinoma (OSCC) in South East Scotland and (b)
      whether this improvement was human papillomavirus (HPV) and p16 subtype
      dependent. METHODS: Clinicopathological characteristics and outcome data for
      patients referred with OSCC from 1999 to 2001 (Cohort-1) and 2003 to 2005 (Cohort
      2) were obtained. Molecular HPV detection and immunohistochemistry for p16 were
      performed from paraffin blocks. RESULTS: Cohort-1 and Cohort-2 contained 118 and
      136 patients, respectively. Kaplan-Meier analysis revealed significantly improved
      survival in Cohort-2 (P<0.0001). Sub-classification according to HPV and p16
      status revealed no improvement in survival in Class-I (HPV-ve/p16-ve; 47
      patients) or Class-III (HPV+ve/p16+ve; 77 patients). However in Class-II
      (HPV+ve/p16-ve; 56 patients) an increase in 5-year cause-specific survival from
      36% in Cohort-1 to 73% in Cohort-2 was detected (P=0.0001).Proportional hazards
      analysis of 217 patients treated radically demonstrated that significant
      variables were p16 (P<0.0001), N stage (P=0.0006) and cohort (P=0.0024). Removing
      cohort from the variables offered to the model showed that, whereas p16
      (P<0.0001) and N stage (P=0.0016) remain significant, chemotherapy (P=0.0163) and
      T stage (P=0.0139) are now significant. This suggests that much of the cohort
      effect is due to the higher use of chemotherapy in the second cohort. CONCLUSION:
      These data suggest that HPV+ve/p16-ve patients constitute a separate subclass of
      OSCC who may particularly benefit from chemotherapy. They imply that p16 status
      cannot be considered a surrogate for HPV status, and those trials to de-escalate
      treatment in HPV+ve OSCC should take p16 status into account.

PMID- 22146524
TI  - Rapid analysis of abused drugs using nanostructured silicon surface assisted
      laser desorption/ionization mass spectrometry.
AB  - This study developed a rapid, sensitive, and matrix-free method for the
      determination of amphetamine (AMP), methamphetamine (MA), codeine (COD), morphine
      (MOR), and ketamine (KET) using nanostructured silicon surface assisted laser
      desorption/ionization mass spectrometry (nSi-MS). The nanostructured silicon
      (nSi) chip used in this study was created by employing the metal-assisted etching
      process. Drug standard tests were applied to the nSi chip platform to evaluate
      the nSi-MS performance, including detection sensitivity, limit of detection,
      linearity, and repeatability. Real urine samples obtained from drug addict
      detainees were directly applied to the nSi chip for drug analysis. By observing
      the nSi-MS spectra, the target drug peaks can be identified; and an antibody pull
      down assay was performed to confirm the specificity of the detected targets. nSi
      MS drug quantification was assayed, yielding comparable results with those from
      using the GC-MS approach. The advantages of applying nSi-MS to analyze AMP, MA,
      COD, MOR, and KET in the urine of addicts are simple, extremely small urine
      volumes (~10 MUL), and a fast analysis procedure (<15 minutes).

PMID- 22146525
TI  - Prevalence of coinfection in children with Epstein-Barr virus-associated
      hemophagocytic lymphohistiocytosis.
AB  - BACKGROUND: The pathology of Epstein-Barr virus-associated hemophagocytic
      lymphohistiocytosis (EBV-HLH) has not been elucidated. The progression of the
      disease could be influenced by coinfection with other pathogens. This study
      investigates the prevalence of cytomegalovirus (CMV), hepatitis B and C,
      bacteria, mycoplasma, fungi, and tuberculosis among EBV-HLH children. DESIGN AND
      METHODS: Clinical and laboratory records of EBV-HLH patients at Beijing
      Children's Hospital between June 2007 and June 2010 were retrospectively
      reviewed. RESULTS: Forty-seven children diagnosed with EBV-HLH were included. The
      average age at diagnosis was 4 years 1 months +/- 3 years 9 months (mean +/- SD).
      CMV-Ab-IgM was positive in 6.7% (3 of 45), bacteria culture was positive in 14.3%
      (6 of 42), fungi culture was positive in 10.7% (3 of 28) patients. Hepatitis B
      virus surface antigen, hepatitis C virus antibody, purified protein derivative,
      and myoplasma antibody-IgM were negative in these patients. Two patients were
      coinfected by 2 pathogens: fungi and bacteria (n = 1), CMV and bacteria (n = 1).
      Four patients died in hospital, among them 2 patients had bacteria culture
      positive results. Only a fraction of the EBV-HLH patients had genetic defects in
      PRF1, UNC13D, and XIAP. CONCLUSIONS: The overall coinfection ratio with EBV-HLH
      was 21.3% in our series (10 of 47), 50% of in hospital deaths (2 of 4) were
      attributable to sepsis. More attention should pay on coinfections in EBV-HLH
      patients, especially bacterial coinfection.

PMID- 22146526
TI  - Acquired bone marrow failure after diphtheria.
AB  - Acquired bone marrow failure can result after infections caused by viruses,
      exposure to toxins, or chemicals. Majority of acquired cases of marrow failure
      labeled as "idiopathic" are probably immune mediated through activated T-cells
      and cytokines. We observed pancytopenia in the second week, after pharyngeal
      diphtheria in a 14-year-old child. Bone marrow examination showed reduced marrow
      precursors affecting all 3 cell lines. There are no clinical cases of
      myelosuppression reported in diphtheria infection and this is probably the first
      reported case of bone marrow failure after diphtheria infection. However, such
      observations merit further evaluation and confirmation by experimental studies.

PMID- 22146527
TI  - Gas-distended stomach masquerading as free air.
AB  - Free air can be an ominous sign of bowel perforation with the fear if resulting
      sepsis. Several radiological signs have been described to aid in interpretation
      including Rigler's sign. We present a case where a large amount of free air was
      felt to be present in a 5 year old post craniopharyngioma resection. Clinically
      free air was not expected. To try and acount for these discrepant findings, the
      nasogastric tube was examined and found to be clogged. Once the nasogastric tube
      functioned, it became evident that the large amount of air was in the stomach
      rather than free in the peritoneal cavity. This case demonstrates a potential
      mimic of free air but also highlights the need to correlate radiographic findings
      and interpretations to the clinical state of the patient.

PMID- 22146528
TI  - Weekend delay in initiation of chemotherapy for acute lymphoblastic leukemia:
      does it matter?
AB  - The Friday afternoon admission of a child with a potential diagnosis of leukemia
      creates perceived delays in treatment initiation. Although generally not felt to
      affect prognosis, the effect of a few days delay in chemotherapy for children
      with acute lymphoblastic leukemia (ALL) has not been fully investigated. We
      retrospectively analyzed 207 patients consecutively diagnosed with ALL at
      Children's Hospital & Research Center Oakland from 1995 to 2007 to determine if
      delay in chemotherapy increased the risk of relapse, death, transfer to the
      intensive care unit, or bacteremia. Friday admission did not significantly delay
      chemotherapy initiation with treatment started at a mean of 4.13+/-2.40 days for
      Friday admits versus 3.72+/-1.57 days for all others (P=0.29). There was no
      significant association between treatment delay days and relapse (P=0.94) or
      death (P=0.55). In Cox regression analysis, treatment delay was not a predictor
      of time to relapse (P=0.80) or longer duration of hospitalization (corrected for
      delay, P=0.15). There were trends toward significant associations between
      treatment delay and bacteremia (P=0.07) and intensive care unit admissions
      (P=0.08), although both were associated with shorter, not longer, treatment
      delays.We were unable to demonstrate a significant effect of delay in
      chemotherapy initiation for pediatric patients with newly diagnosed ALL on the
      examined outcome variables.

PMID- 22146529
TI  - A case of retroperitoneal immature teratoma with nephroblastic components.
AB  - The presence of nephroblastic components is extremely rare in retroperitoneal
      teratomas. We described an unusual case of right retroperitoneal immature
      teratoma with nephroblastic components in a 2-month-old Japanese girl.
      Approximately 15% of tumor was composed of nephroblastic components within
      immature teratoma components. Although overlap of histopathological findings
      between teratomas with nephroblastic components and teratoid Wilms tumors, which
      have heterologous elements in >50% of the tumor, occasionally exist, the most
      distinct feature of teratoma is the presence of organoid arrangement. The
      prognosis of retroperitoneal teratomas with nephroblastic components has not yet
      been established, therefore, additional case studies are needed.

PMID- 22146530
TI  - An assessment of end-of-life-care training: should we consider a cross
      fellowship, competency-based simulated program?

PMID- 22146531
TI  - Preoperative chemotherapy with doxorubicin in Wilms tumor.
AB  - BACKGROUND: Vincristine and actinomycin-D have long been used as the preoperative
      chemotherapy before nephrectomy in patients with Wilms tumor (WT). Actinomycin-D
      is not readily found in Turkey, and delay in treatment, occurring basically from
      commercial and marketing problems, prompted us to administer alternatives such as
      doxorubicin, another antitumor antibiotic available in Turkey, to our newly
      diagnosed patients with WT. PROCEDURE: Between November 2009 and January 2011, 12
      consecutive patients with WT were included in the study. Preoperative
      chemotherapy consisted of vincristine (1.4 mg/m, days 1, 8, 15, and 22) and
      doxorubicin (20 mg/m, 1 to 3 d). RESULTS: All renal tumors showed shrinkage
      drastically after 4 weeks of preoperative chemotherapy. Surgery of all the
      patients was uneventful and without any complications. At the end of the median
      follow-up time of 8 months (range, 6 to 17 mo), all patients are in remission
      without a sign of the disease. CONCLUSIONS: Preoperative chemotherapy consisting
      of vincristine and doxorubicin seems to be successful as a preoperative treatment
      in achieving shrinkage and reducing the risk of surgical complications. On the
      basis of the promising results in our study, it is worth administering a similar
      regimen with further follow-up in larger populations.

PMID- 22146532
TI  - Pretransplant conditioning with Campath-1H (alemtuzumab) in pediatric matched
      unrelated hematopoietic stem cell transplants: an institutional experience.
AB  - Graft versus host disease (GVHD) remains a major cause of mortality and morbidity
      after matched unrelated hematopoietic stem cell transplantation (HSCT). Campath-1
      H (alemtuzumab), a humanized monoclonal antibody to CD52 antigen, is thought to
      reduce GVHD incidence through in vivo T-cell depletion. Through the same
      mechanism it can potentially increase the risk of relapse by reducing the graft
      versus leukemia effect and possibly increase the risk of infection due to delayed
      immune recovery. A retrospective case analysis of 17 pediatric matched unrelated
      HSCTs done in our institution between January 2003 and June 2009 with Campath-1H
      as part of the pretransplant conditioning regimen was conducted. Grade I-II acute
      GVHD was noted in 29.4% of the HSCTs. No patient developed chronic GVHD. All but
      one patient with severe aplastic anemia engrafted. A relapse of primary disease
      was noted in 35.3% of the transplants. Three patient deaths were due to relapse
      and 1 due to disseminated varicella infection. Overall survival was 100% and 94%
      at 100 days and 1 year, respectively. Our experience suggests Campath-1H used as
      part of pretransplant conditioning regimen in pediatric unrelated HSCTs
      effectively reduces the risk of serious GVHD with no apparent increase in life
      threatening infections or relapse compared with that reported with conventional
      regimens. Larger studies, with longer duration of follow-up, are required to
      further assess its role with regards to graft versus leukemia effect and to
      establish if the decreased incidence of GVHD and infectious complications is
      sustained in larger cohorts.

PMID- 22146533
TI  - Bloody nipple discharge in 2 infants with interesting cytologic findings of
      extramedullary hematopoiesis and hemophagocytosis.
AB  - Bloody nipple discharge in the infantile period is an uncommon finding. Despite
      its stressful course to the parents, it is generally a benign condition with a
      spontaneous resolution. The approach to bloody nipple discharge in the infantile
      period is well documented in the literature even though the number of these cases
      is limited. We report 2 infants with unilateral bloody nipple discharge. Their
      physical examination, laboratory, and ultrasound findings were normal but the
      cytologic examinations of the discharge revealed signs of extramedullary
      hematopoiesis and hemophagocytosis. These extraordinary findings made us
      brainstorm on the probable ongoing processes in the infantile breast tissue.

PMID- 22146534
TI  - Pseudohyperphosphatemia associated with high-dose liposomal and lipid complex
      amphotericin B when tested with Synchron LX 20 (Beckman/Coulter) phosphorous
      assay.
AB  - Although case reports of hyperphosphatemia have been previously described in
      patients receiving liposomal amphotericin B, this has not been reported in
      patients receiving the lipid complex formulation. We report a case of
      hyperphosphatemia that persisted despite switching from liposomal to lipid
      complex amphotericin B in a child with invasive zygomycosis. This case suggests
      that in the context of acute renal dysfunction, hyperphosphatemia may also be
      observed with lipid complex amphotericin B. This case highlights the importance
      of differentiating between pseudohyperphosphatemia and hyperphosphatemia to
      prevent complications.

PMID- 22146535
TI  - Preclinical testing of tandutinib in a transgenic medulloblastoma mouse model.
AB  - Overexpression of platelet-derived growth factor receptor alpha (PDGFR-A) has
      been documented in association with primary tumors and metastasis in
      medulloblastoma. Tumors from our genetically engineered sonic hedgehog-driven
      medulloblastoma mouse model overexpress PDGFR-A in primary tumors and thus this
      mouse model is a good platform with which to study the role of PDGFR-A in this
      central nervous system malignancy. We hypothesized that inhibition of PDGFR-A in
      medulloblastoma can slow or inhibit tumor progression in living individuals. To
      test our hypothesis, we targeted PDGFR-A mediated tumor growth in vitro and in
      vivo using the tyrosine kinase inhibitor, tandutinib (MLN-518), which strongly
      inhibits PDGFR-A. Although PDGFR-A inhibition by this agent resulted in reduced
      mouse tumor cell growth and increased apoptosis in vitro, and reduced tumor cell
      proliferation in vivo, tandutinib did reduce tumor volume at the doses tested
      (360 mg/kg) in vivo. Thus, tandutinib may be an agent of interest for sonic
      hedgehog-driven medulloblastoma if a synergistic drug combination can be
      identified.

PMID- 22146536
TI  - ACS6, a Hydrogen sulfide-donating derivative of sildenafil, inhibits homocysteine
      induced apoptosis by preservation of mitochondrial function.
AB  - BACKGROUND: The hydrogen sulfide-releasing sildenafil, ACS6, has been
      demonstrated to inhibit superoxide formation through donating hydrogen sulfide
      (H2S). We have found that H2S antagonizes homocysteine-induced oxidative stress
      and neurotoxicity. The aim of the present study is to explore the protection of
      ACS6 against homocysteine-triggered cytotoxicity and apoptosis and the molecular
      mechanisms underlying in PC12 cells. METHODS: Cell viability was determined by
      Cell Counting Kit-8 assay. Cell apoptosis was observed using the chromatin dye
      Hoechst 33258 and analyzed by Flow Cytometry after propidium iodide staining.
      Mitochondrial membrane potential was monitored using the fluorescent dye Rh123.
      Intracellular reactive oxygen species were determined by oxidative conversion of
      cell permeable 2',7'-dichlorfluorescein-diacetate to fluorescent 2',7'
      dichlorfluorescein. The expression of cleaved caspase-3 and bcl-2 and the
      accumulation of cytosolic cytochrome c were analyzed by Western blot. RESULTS: We
      show that ACS6 protects PC12 cells against cytotoxicity and apoptosis induced by
      homocysteine and blocks homocysteine-triggered cytochrome c release and caspase-3
      activation. ACS6 treatment results in not only prevention of homocysteine-caused
      mitochondrial membrane potential (Deltapsi) loss and reactive oxygen species
      (ROS) overproduction but also reversal of Bcl-2 down-expression. CONCLUSIONS:
      These results indicate that ACS6 protects PC12 cells against homocysteine-induced
      cytotoxicity and apoptosis by preservation of mitochondrial function though
      inhibiting both loss of Deltapsi and accumulation of ROS as well as modulating
      the expression of Bcl-2. Our study provides evidence both for a neuroprotective
      effect of ACS6 and for further evaluation of ACS6 as novel neuroprotectants for
      Alzheimer's disease associated with homocysteine.

PMID- 22146537
TI  - Early cognitive function, recovery and well-being after sevoflurane and xenon
      anaesthesia in the elderly: a double-blinded randomized controlled trial.
AB  - BACKGROUND: The postoperative cognitive function is impaired in elderly patients
      after general anaesthesia. The fast recovery after xenon anaesthesia was
      hypothesized to be advantageous in this scenario. We compared early postoperative
      cognitive function after xenon and sevoflurane anaesthesia in this study.
      METHODS: The study was approved by the local ethics committee and written
      informed consent was obtained from each patient. Patients aged 65-75 years (ASA I
      III) scheduled for elective surgery (duration 60-180 min) were enrolled.
      Investigators performing cognitive testing and patients were blinded towards
      allocation to either xenon or sevoflurane anaesthesia. Baseline assessment of
      cognitive function was carried out 12-24 h before the operation. The results were
      compared to follow-up tests 6-12 and 66-72 h after surgery. Primary outcome
      parameter was the subtest "Alertness" of the computerized Test of Attentional
      Performance (TAP). Secondary outcome parameters included further subtests of the
      TAP, several Paper-Pencil-Tests, emergence times from anaesthesia, modified
      Aldrete scores and patients' well-being. RESULTS: 40 patients were randomized and
      equally allocated to both groups. No significant differences were found in the
      TAP or the Paper-Pencil-Tests at 6-12 and 66-72 h after the operation. All
      emergence times were faster after xenon anaesthesia. The modified Aldrete scores
      were significantly higher during the first hour in the xenon group. No difference
      in well-being could be detected between both groups. CONCLUSIONS: The results
      show no difference in the incidence of postoperative cognitive dysfunction (POCD)
      after xenon or sevoflurane anaesthesia. Emergence from general anaesthesia was
      faster in the xenon group.

PMID- 22146538
TI  - Physical properties of [Formula: see text] polymer electrolytes: nuclear magnetic
      resonance investigation and comparison with [Formula: see text].
AB  - The physical properties of the ionic conductor [Formula: see text], obtained by
      dissolution of lithium trifluoromethanesulphonylimide in poly(propylene oxide),
      have been investigated for several values of n. The glass transition temperature
      [Formula: see text] has been established from both DSC and NMR techniques. The
      diffusion coefficients of [Formula: see text]-containing species have been
      determined by the pulsed magnetic field gradient technique. The behaviour of the
      proton relaxation time [Formula: see text] versus temperature and concentration
      has been correlated to the glass temperature. The behaviour of the proton
      transverse relaxation function, obtained by the spin-echo technique, has been
      interpreted using a simple model in which two regimes and consequently two
      transverse relaxation times coexist and are assigned to the 'entangled' and 'non
      entangled' parts of the high-molecular-weight polymer chains investigated.

PMID- 22146539
TI  - Quantifying the biodistribution of nanoparticles.

PMID- 22146540
TI  - Quantifying the biodistribution of nanoparticles.

PMID- 22146542
TI  - Nanopores: water flow at the flip of a switch.

PMID- 22146543
TI  - Lipid structures: a brief history of multisomes.

PMID- 22146544
TI  - Simple model of forebrain ischemia in mouse.
AB  - The availability of genetically engineered mice allows the unraveling of the role
      of specific proteins in mechanisms of ischemic brain injury. Due to the high
      variability of their vascular anatomy, mouse models of global cerebral ischemia
      are rather complex. In the present study, we describe a simple model of mouse
      forebrain ischemia where the bilateral common carotid artery occlusion (BCCO) is
      combined with isoflurane-induced hypotension. The forebrain ischemia was induced
      by BCCO that was preceded by increase of the isoflurane level from 1.5% to 5% in
      the respiratory gases. This caused a decrease of the mean arterial blood pressure
      (MABP) to about 30mmHg and the cerebral blood flow dropped to 5% of the control
      after the BCCO. During the 10min ischemic period both MABP and CBF remained
      stable and the reperfusion was induced by reducing the isoflurane level to 0%
      followed by removal of the carotid clamps. Mice were allowed 1, 2, 3 or 5 days
      survival followed by histologic analysis. The number of CA1 uninjured neurons was
      assessed utilizing a stereological approach. Neurodegeneration was observed at 2
      days after the onset of reperfusion. At 3 days of recovery, about 40% of neurons
      survived and the cell death did not further increase at 5 days. Degenerative
      neurons were also detected in the striatum and sporadically in the cortex. This
      study demonstrates the feasibility of using the described model in mice that can
      be utilized to examine the effect of new neuroprotective compounds or use
      transgenic animals to test new hypothesis.

PMID- 22146545
TI  - Efficacy of bevacizumab against interface neovascularization after deep anterior
      lamellar keratoplasty.
AB  - PURPOSE: We report a case of neovascularization at the interface after a deep
      anterior lamellar keratoplasty and its regression after a single bevacizumab
      injection. METHODS: Case report. RESULTS: We present a case of neovascularization
      and bleeding at the interface 2 days after a deep anterior lamellar keratoplasty
      for herpetic disease that was completely reversed by a single injection of
      bevacizumab at the interface. CONCLUSIONS: Corneal neovascularization is a
      typical sign of herpetic disease and one of the most important risk factors that
      can contribute to corneal graft failure. Close follow-up of patients at risk is
      necessary to detect and treat this complication as soon as possible to achieve a
      good outcome. Bevacizumab seems to be a successful and safe therapeutic option.

PMID- 22146546
TI  - Interstitial keratitis secondary to severe hidradenitis suppurativa responding to
      adalimumab.

PMID- 22146547
TI  - Regional conjunctivectomy with postoperative mitomycin C to treat chronic
      hyperemic conjunctiva.
AB  - PURPOSE: To introduce a new surgical technique to treat persistent irreversible
      hyperemic conjunctiva and evaluate the clinical results. METHODS: A total of 571
      patients with chronic conjunctival injection refractory to medical treatment were
      included. During surgery of the medial bulbar area, the conjunctiva and Tenon
      capsule were excised from the limbus to near the plica semilunaris. The lateral
      conjunctiva and Tenon capsule were removed from the limbus to beside the lateral
      canthus. Mitomycin C 0.02% was applied 4 times daily for 2 to 5 days
      postoperatively. The complications and surgical results of regional
      conjunctivectomy were evaluated. RESULTS: A total of 1815 ocular regions of 571
      patients underwent regional conjunctivectomy. The mean period of conjunctival
      injection was 9.9 +/- 6.9 years. The patients were followed for 2 to 27 months
      (average, 12.9 months). The overall postoperative satisfaction rate was 94.6%;
      328 regions (18.1%) underwent surgical revision for growth of fibrovascular scar
      tissue. No serious complications developed intraoperatively. Postoperative
      complications included intraocular pressure elevations (98 of 571; 17.2%),
      development of granuloma (153 of 1815; 8.4%), transient subjective visual
      decreases (43 of 571; 7.5%), pigment deposition (96 of 1815; 5.3%), scleral
      calcification (70 of 1815; 3.9%), and diplopia because of adhesion esotropia (9
      of 571; 1.6%). All complications were managed surgically and/or medically. No
      permanent deficits resulted. CONCLUSIONS: Regional conjunctivectomy with
      postoperative mitomycin C 0.02% can be useful to successfully treat patients with
      chronic hyperemic conjunctivae refractory to medical treatment.

PMID- 22146548
TI  - Descemet membrane endothelial transfer: "free-floating" donor Descemet
      implantation as a potential alternative to "keratoplasty".
AB  - PURPOSE: To describe corneal clearance after reendothelialization of the
      recipient posterior stroma, by a "free-floating" donor Descemet roll in the
      recipient anterior chamber after Descemet membrane endothelial keratoplasty
      (DMEK), as a potential new approach in managing corneal endothelial disorders.
      METHODS: An 80-year-old woman underwent DMEK for Fuchs endothelial dystrophy.
      Within hours after the surgery, a "free-floating" Descemet roll was observed in
      the recipient anterior chamber. Because the operated eye had low visual
      potential, the patient requested to await the clinical outcome, which was
      monitored by biomicroscopy, and endothelial cell density (ECD) and pachymetric
      measurements were evaluated. RESULTS: Within the first few weeks after DMEK, the
      transplanted cornea showed diffuse corneal edema with a central pachymetry of
      more than 1000 MUm. From 1 month onward, the transplanted cornea started to clear
      in the inferior quadrants. At 6 months, only remnant edema was present in the
      superior far periphery, pachymetry across the cornea had returned to normal, and
      ECD measured 830 cells per square millimeter. CONCLUSIONS: The performance of a
      descemetorhexis followed by the implantation of a "free-floating" Descemet roll
      in the recipient anterior chamber, tentatively named Descemet membrane
      endothelial transfer, may have potential as a "no-keratoplasty" surgical concept
      in the management of corneal endothelial disorders.

PMID- 22146549
TI  - Descemet membranotomy with an Nd:YAG laser can be used to treat pre-Descemet
      hemorrhage.

PMID- 22146550
TI  - KeraRing intrastromal corneal ring segments for correction of keratoconus.
AB  - PURPOSE: Intrastromal corneal ring segments (ICRSs) are small arc-like implants
      that are being used increasingly as a minimally invasive treatment for patients
      with keratoconus. This study assessed the effectiveness of KeraRing implants, a
      type of ICRS, to treat keratoconus. METHODS: Retrospective case series
      descriptive study of 43 patients (55 eyes) with keratoconus who underwent
      KeraRing implantation from February 2008 to June 2009. Patients who had
      intraoperative or postoperative complications and/or did not complete at least 6
      months of follow-up were excluded. All patients underwent complete ophthalmologic
      examinations that included measurement of the uncorrected visual acuity (UCVA),
      best spectacle-corrected visual acuity (BSCVA), manifest refraction, and
      keratometry before and 2 days, 2 weeks, 1 month, and 3 and 6 months after
      surgery. The ring segments were chosen based on a nomogram from the manufacturer.
      RESULTS: Six months postoperatively, the mean UCVA increased significantly (P <
      0.05) from 0.10 +/- 0.11 to 0.32 +/- 0.25 and the mean BSCVA increased from 0.36
      +/- 0.23 to 0.57 +/- 0.24 (P < 0.05). The mean spherical refractive error
      significantly (P < 0.05) improved from -4.85 +/- 2.90 diopters (D) to -1.89 +/-
      2.68 D, and the mean cylindrical refractive error significantly (P < 0.05)
      improved from -3.65 +/- 1.70 D to -2.60 +/- 1.62 D. The mean spherical equivalent
      significantly (P < 0.05) decreased from -6.68 +/- 2.93 D to -3.19 +/- 2.75 D, and
      the mean keratometry value decreased from 51.83 +/- 4.14 D to 47.27 +/- 3.68 D.
      The improvement in the UCVA and BSCVA continued over the 6-month postoperative
      period, but significant changes occurred only during the first 3 months. These
      changes occurred in patients with all grades of keratoconus. CONCLUSIONS:
      KeraRing implantation provided significant improvement in visual acuity,
      spherical equivalent, and keratometry results. This ICRS is an effective
      treatment for managing keratoconus and might delay or even avoid the need for
      penetrating keratoplasty.

PMID- 22146551
TI  - Familial peripheral keratopathy without PAX6 mutation.
AB  - PURPOSE: To describe the clinical features of a familial abnormality of the
      corneal stem cells and to investigate the role of PAX6 mutations in the affected
      family members. METHODS: A family with multiple generations of peripheral
      keratopathy was evaluated. Because of the corneal phenotypic similarity to
      aniridia-related keratopathy, it was hypothesized that the affected patients
      might have a dominantly inherited mutation of PAX6 on chromosome 11. Commercial
      sequencing of germline DNA from 1 affected family member did not identify any
      PAX6 mutations in the exons or intron-exon boundary regions. Because the
      commercial analysis is not designed to identify PAX6 deletions, germline DNA was
      collected from 5 unaffected and 2 additional affected family members. DNA repeat
      markers in the region of PAX6 were analyzed to determine whether this chromosomal
      region segregates with the disease phenotype. RESULTS: Affected family members
      with this autosomal dominant peripheral corneal abnormality showed evidence of
      progressive corneal stem cell dysfunction. Several individuals demonstrated
      corectopia, and 1 individual had ectropion uvea but no other iris or ocular
      abnormalities associated with aniridia. Genotyping data of affected and
      unaffected family members demonstrated that the PAX6 region does not segregate
      with the disease phenotype. CONCLUSIONS: The features of this autosomal dominant
      abnormality show some similarity to aniridia, although the classic
      characteristics of severe iris hypoplasia and macular hypoplasia are absent.
      Mutational screening and genotyping could not conclusively clarify a role for
      PAX6 in this disease phenotype, suggesting that it is a distinct clinical and
      genetic disease entity, not a variant of aniridia.

PMID- 22146552
TI  - Outcomes of Descemet stripping automated endothelial keratoplasty in patients
      with previous glaucoma drainage device insertion.
AB  - PURPOSE: To report the outcomes of Descemet stripping automated endothelial
      keratoplasty (DSAEK) in patients with a previously inserted glaucoma drainage
      device (GDD). METHODS: The clinical records of patients who had DSAEK surgery
      with a history of GDD insertion were reviewed. RESULTS: Eleven eyes of 10
      patients (7 men and 3 women) were included. The mean age for DSAEK surgery was
      67.2 +/- 20.4 years (range, 22-93 years). The mean follow-up after DSAEK surgery
      was 20.2 +/- 10.7 months (range, 3-37 months). Preoperative mean logarithm of the
      minimum angle of resolution (logMAR)-corrected distance visual acuity was 1.8 +/-
      0.6 (range, 20/100 to hand motions), and this improved to 0.9 +/- 0.8 (range,
      20/40 to hand motions) at the final follow-up (P < 0.01). There was no
      statistical difference in mean pre-DSAEK versus final post-DSAEK intraocular
      pressure (P = 0.88). Six of 11 eyes (54.5%) had double GDD insertion before DSAEK
      surgery. GDD tubes were trimmed in 6 eyes (54.5%), and no eyes required further
      glaucoma surgical intervention after DSAEK surgery. Postoperative complications
      included early postoperative graft dislocation in 4 eyes (36.4%) that were
      successfully repositioned. Four eyes (36.4%) had an episode of endothelial
      rejection, with 2 patients (18.2%) requiring repeat endothelial keratoplasty for
      endothelial failure. The mean donor endothelial cell count was 2740 cell per
      square millimeter preoperatively and reduced to 858 cells per square millimeter
      at the final follow-up, a significant mean reduction of 69%. This was
      significantly greater than previously reported endothelial cell loss after DSAEK
      alone at our institution. CONCLUSIONS: Although surgery may be more challenging,
      the presence of GDD is not a contraindication to DSAEK surgery. In this series,
      there was a high rate of dislocation that was successfully managed with
      rebubbling. DSAEK seems to be a reasonable alternative to penetrating
      keratoplasty for corneal decompensation after GDD.

PMID- 22146553
TI  - Role of the TCF4 gene intronic variant in normal variation of corneal
      endothelium.
AB  - PURPOSE: To identify early features of Fuchs endothelial dystrophy (FED) in
      carriers of the rs613872(G) transcription factor 4 gene (TCF4) aged 20 to 21
      years. METHODS: Prospective cohort study of people aged 20 to 21 years previously
      enrolled in the Western Australia Pregnancy (Raine) Cohort. Specular microscopy
      was performed using a noncontact specular microscopy (EM-3000; Tomey, Nagoya,
      Japan). Individual genotype data were extracted from the genome-wide Illumina 660
      Quad Array. Analysis of the association between the rs613872 risk allele in TCF4
      and specular microscopic measurements was conducted. RESULTS: Association between
      the rs613872 risk allele and corneal endothelial cell density (CD) as well as the
      coefficient of variation in cell shape was the main outcome measure. Genotype and
      specular microscopic data were available for a total of 445 participants (46%
      women). The median CD was 2851 and 2850 cells per square millimeter in the right
      and left eyes, respectively. No significant differences between intereye
      variability in endothelial CD were seen (right eye to left eye correlation =
      0.64); however, a significant difference in variability of endothelial CD between
      men and women was observed (male: OD, 2839 +/- 124 cells/mm2 and OS, 2845 +/- 124
      cells/mm2 vs. female: OD, 2838 +/- 134 cells/mm2 and OS, 2842 +/- 132 cells/mm2;
      OD, P = 0.0013 and OS, P = 0.0016). Eleven individuals were homozygous for the
      rs613872 risk allele. We found no association between rs613872 genotype and CD or
      coefficient of variation. One of 11 homozygous GG individuals was found to have a
      gutta in 1 sample field on specular microscopy, whereas 2 of 297 TT individuals
      also had a gutta each in 1 sample field. CONCLUSIONS: We were unable to detect an
      association between TCF4 rs613872 genotype and the variation in corneal
      endothelial CD or variation in cell morphology in a healthy young adult
      population.

PMID- 22146555
TI  - Angelica sinensis isolate SBD.4: composition, gene expression profiling,
      mechanism of action and effect on wounds, in rats and humans.
AB  - This report characterizes an aqueous isolate (SBD.4) of one of the most broadly
      used Chinese medicinal herbs, Angelica sinensis, from the perspective of its
      application in skin and wound care. SBD.4 has been chemically defined and was
      found to increase the strength of healed wounds in retired breeder (older) rats.
      Furthermore, the mechanism of action of this Angelica sinensis isolate was tested
      in the zebrafish angiogenesis model, and in human skin substitutes by DNA
      microarray, revealing a bioactivity profile consistent with skin repair and
      regeneration. When combined with several types of wound dressings, SBD.4
      increased type I collagen production in human dermal fibroblasts, and when
      formulated in nanosilver hydrocolloid dressing, it was found effective in chronic
      ulcer management in humans, demonstrating that botanical high-tech wound
      dressings can be successfully developed to improve the treatment of chronic
      lesions in humans.

PMID- 22146554
TI  - Serum xylosyltransferase 1 level increases during early posttraumatic
      osteoarthritis in mice with high bone forming potential.
AB  - Increased proteoglycan (PG) synthesis is essential for the stimulation of
      cartilage repair processes that take place during the reversible phase of
      osteoarthritis (OA). In articular cartilage, xylosyltransferase 1 (Xylt1) is the
      key enzyme that initiates glycosaminoglycan (GAG) chain synthesis by transferring
      the first sugar residue to the PG core protein. Biological activity of PGs is
      closely linked to GAG biosynthesis since their polyanionic nature directly
      contributes to the proper hydration and elastic properties of the cartilage
      tissue present at the articular interface. The aim of this study was to
      investigate whether variations in the level of Xylt1 present in serum can be used
      to predict OA disease progression. The influence of bone forming activity on the
      systemic release of this enzyme was addressed by experimentally-inducing OA in
      mice of two different genetic backgrounds that were previously characterized for
      their distinct bone metabolism: C57BL/6J (B6, high bone remodelers) or C3H/HeJ
      (C3H, high bone formers). Serum was collected after medial meniscectomy or sham
      surgeries in young adult mice of these two strains over a period of 3.5months at
      which point knee histopathology was assessed. A significant increase in serum
      Xylt1 levels observed shortly after meniscectomy positively correlated with
      severe cartilage damage evaluated by histological assessment at later time points
      in mice of the C3H background. In contrast, no temporal regulation of Xylt1 level
      was found between meniscectomies and control surgeries in B6 mice, which
      developed OA at a slower rate. Additionally, longitudinal evaluation of the serum
      levels of other markers of cartilage/bone metabolism (C1,2C, osteocalcin) did not
      reveal any association with late knee damages. Our results strongly support the
      idea that serum Xylt1 has a clinical value for monitoring risk of OA progression
      in young adults with high bone forming potential. Ultimately, the understanding
      of posttraumatic mechanisms regulating PG synthesis and their modification by GAG
      will be essential so that interventions that stimulate cartilage regrowth can be
      undertaken prior to irreversible destruction of the joint tissue. This article is
      part of a Special Issue entitled "Osteoarthritis".

PMID- 22146556
TI  - Odontoid fracture following a fall in an elderly man.
AB  - The patient was a 79-year-old man with a chief complaint of neck pain after a
      fall. Three days following the fall, the patient was seen in the emergency
      department, where computed tomography imaging of the head and radiographs of the
      cervical spine were completed. The patient was subsequently referred to a
      physical therapist. Due to concern for a possible undetected cervical spine
      fracture, the patient was immediately referred to his physician. Magnetic
      resonance imaging demonstrated a type II fracture of the odontoid.

PMID- 22146557
TI  - Issues in the interpretation of associations of PCBs and IQ.
AB  - The literature concerning the relationship between polychlorinated biphenyl (PCB)
      exposure and Intelligence (IQ) is not entirely consistent. Two studies showed
      inverse associations between PCBs and IQ in cohorts of children whose mothers
      consumed Great Lakes fish contaminated with PCBs and other organochlorines
      (Jacobson & Jacobson 1996; Stewart et al. 2008). Another study from the general
      US population, where women were exposed to background levels of PCBs, showed no
      association between PCBs and IQ (Gray et al. 2005). The current report examines
      two potential sources of inconsistency across studies: 1) confounding with non
      PCB organochlorines [Hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene
      (DDE), and Mirex]; and 2) the presence of negative confounding (i.e., suppressor
      variables). The former could confound PCBs and lead to spurious associations
      (Type I errors), while the latter could suppress PCB associations and obscure
      true associations (Type II errors). These issues were explored through the
      analysis of associations between placental levels of organochlorines and IQ in
      children at 9 and 11 years of age in the Oswego study. Neither DDE nor mirex was
      related to lower IQ at either age; PCBs predicted lower IQ at both ages; and
      hexachlorobenzene (HCB) appeared as a significant predictor of IQ at the 11-year
      assessment. However, analysis of the IQ data set as a whole showed that both PCBs
      and HCB predicted lower IQ in a generally independent fashion. There was,
      however, overlap in the variance in some cases, and the pattern of findings
      between the two was remarkably similar. These results may provide some evidence
      for the potential involvement of non-PCB organochlorines in the Oswego study. To
      explore negative confounding, we analyzed the relationships between PCB exposure
      and demographic variables as well as the unadjusted and adjusted relationships
      between PCB and IQ. Results revealed that placental PCB levels were associated
      with older mothers who were more educated and came from higher socioeconomic
      strata. Due to this fact, unadjusted relationships between PCBs and IQ appeared
      null or slightly positive. After control for confounders, several significant
      negative associations between PCBs and IQ were revealed. These data might suggest
      that inadequate control for confounders in PCB studies, where negative
      confounding is present, may bias results toward the null (Type II error) rather
      than spurious associations (Type I error). This pattern of confounding with PCB
      exposure in the Oswego study also has implications for the assessment of risk.
      The most highly exposed children came from families with somewhat higher
      socioeconomic status, and tended to score in the average to above-average range,
      well above IQ scores that are considered "at risk." Further, such children were
      exposed prenatally to PCBs through maternal consumption of PCB-contaminated Great
      Lakes fish in the early 1990s, when PCB levels were higher than today.

PMID- 22146558
TI  - Size-dependent plasmonic responses of single gold nanoparticles for analysis of
      biorecognition.
AB  - We report the use of plasmonic responses of single gold nanoparticles (AuNPs)
      with various sizes for the analysis of biomolecular recognition. We also describe
      the relationship between particle size and plasmonic response induced by the
      binding of receptors and target analytes. To investigate the plasmonic response
      of AuNPs, Rayleigh light scattering spectra were collected from individual AuNPs
      using a dark-field microspectroscopy system. Using prostate-specific antigen
      (PSA) as a model, the linear dynamic range was obtained in the concentration
      range of 10(-4) to 10 ng/ml, with the smallest detectable concentration at 0.1
      pg/ml corresponding to localized surface plasmon resonance (LSPR) lambda(max)
      shifts of approximately 2.95 nm. This result indicates that individual AuNPs can
      be used for development of a very sensitive, robust, simple, and label-free
      biosensor to detect protein biomarkers. Furthermore, the method possesses great
      potential for monitoring other biological interactions.

PMID- 22146559
TI  - Stable isotope liquid chromatography-tandem mass spectrometry assay for fatty
      acid amide hydrolase activity.
AB  - Fatty acid amide hydrolase (FAAH) is the main enzyme responsible for the
      hydrolysis of the endocannabinoid anandamide (arachidonoyl ethanolamide, AEA) to
      arachidonic acid (AA) and ethanolamine (EA). Published FAAH activity assays
      mostly employ radiolabeled anandamide or synthetic fluorogenic substrates. We
      report a stable isotope liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      assay for specific, sensitive, and high-throughput capable FAAH activity
      measurements. The assay uses AEA labeled with deuterium on the EA moiety (d4-AEA)
      as substrate and measures the specific reaction product tetradeutero-EA (d4-EA)
      and the internal standard 13C2-EA. Selected reaction monitoring of m/z 66->m/z 48
      (d4-EA) and m/z 64->m/z 46 (13C2-EA) in the positive electrospray ionization mode
      after liquid chromatographic separation on a HILIC (hydrophilic interaction
      liquid chromatography) column is performed. The assay was developed and
      thoroughly validated using recombinant human FAAH (rhFAAH) and then was applied
      to human blood and dog liver samples. rhFAAH-catalyzed d4-AEA hydrolysis obeyed
      Michaelis-Menten kinetics (K(M)=12.3 MUM, V(max)=27.6 nmol/min mg). Oleoyl
      oxazolopyridine (oloxa) was a potent, partial noncompetitive inhibitor of rhFAAH
      (IC50=24.3 nM). Substrate specificity of other fatty acid ethanolamides decreased
      with decreasing length, number of double bonds, and lipophilicity of the fatty
      acid skeleton. In human whole blood, we detected FAAH activity that was inhibited
      by oloxa.

PMID- 22146560
TI  - The LUMO-derived band of the [Formula: see text] phases.
AB  - The LUMO-derived band of the [Formula: see text] compound was investigated by
      means of x-ray and UV photoemission and photoelectric yield spectroscopies. A
      double-peak structure is found, with peak maxima at 1.1 eV and 0.35 eV. The
      relative magnitude of the two peaks is strongly temperature dependent: a large
      transfer of spectral weight from the lower- to the higher-binding-energy peak
      takes place upon cooling to 110 K. The peaks are tentatively attributed to the
      dimer and the polymeric phase respectively. However the behaviour as a function
      of temperature does not agree with the metastability of the dimer phase at room
      temperature. The position of the Fermi level is compatible with a correlated
      system on the border of the metal - insulating transition.

PMID- 22146561
TI  - NLRP3 E311K mutation in a large family with Muckle-Wells syndrome--description of
      a heterogeneous phenotype and response to treatment.
AB  - INTRODUCTION: Muckle-Wells syndrome (MWS) is an inherited autoinflammatory
      disease characterized by fever, rash, arthralgia, conjunctivitis, sensorineural
      deafness and potentially life-threatening amyloidosis. The NLRP3/CIAS1 E311K
      mutation caused a heterogeneous phenotype of MWS in a large family. This study
      analyzes the clinical spectrum, patterns of inflammatory parameters and reports
      on response to treatment. METHODS: A total of 42 patients and family members were
      screened for the presence of the NLRP3 mutation. Clinical symptoms were reviewed
      in all family members. Classical (erythrocyte sedimentation rate (ESR, C-reactive
      protein (CRP)) and novel MWS inflammatory markers (serum amyloid A (SAA),
      cytokines, cytokine receptor levels) were determined. Patients were treated with
      the IL-1 inhibitors Anakinra or Canakinumab. RESULTS: All 13 clinically affected
      patients were heterozygous carriers of the amino acid substitution
      p.Glu311Lys/E311K encoded by exon 3 of the NLRP3 gene, but none of the healthy
      family members. Disease manifestations varied widely. Except for one child, all
      carriers suffered from hearing loss and severe fatigue. TNF-alpha, IL-6, TNF-RI,
      and TNF-RII levels as well as SAA were elevated in three, two, one, six and ten
      patients, respectively. Both clinical and laboratory parameters responded quickly
      and sustainedly to treatment with Anakinra or Canakinumab. CONCLUSION: The NLRP3
      E311K mutation is associated with a heterogeneous clinical spectrum, which may
      expand the view on MWS presentation. The leading symptom was hearing loss.
      Pericarditis, a rare but severe clinical feature of MWS, was diagnosed in three
      patients. One patient had a severe course, which led to renal failure secondary
      to amyloidosis. IL-1 inhibition leads to rapid and sustained improvement of
      symptoms.

PMID- 22146562
TI  - Hyperbaric oxygen therapy for traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major public health issue. The complexity of
      TBI has precluded the use of effective therapies. Hyperbaric oxygen therapy
      (HBOT) has been shown to be neuroprotective in multiple neurological disorders,
      but its efficacy in the management of TBI remains controversial. This review
      focuses on HBOT applications within the context of experimental and clinical TBI.
      We also discuss its potential neuroprotective mechanisms. Early or delayed
      multiple sessions of low atmospheric pressure HBOT can reduce intracranial
      pressure, improve mortality, as well as promote neurobehavioral recovery. The
      complimentary, synergistic actions of HBOT include improved tissue oxygenation
      and cellular metabolism, anti-apoptotic, and anti-inflammatory mechanisms. Thus
      HBOT may serve as a promising neuroprotective strategy that when combined with
      other therapeutic targets for TBI patients which could improve long-term
      outcomes.

PMID- 22146563
TI  - Congenital total absence of the quadriceps muscle and patella: a case report with
      computed tomography scan and three-dimensional reconstructions.
AB  - In this study, we present three-dimensional computed tomography (CT) scan image
      findings of a case with congenital total absence of the quadriceps muscle and
      patella and partial absence of the sartorius muscle, which caused fixed flexion
      contracture of the knee joint. Physical examination, radiography, three
      dimensional CT scan, and chromosome analysis of the patient were done. On
      physical examination, the knee joint was at 85 degree fixed flexion contracture.
      Radiographic views demonstrated soft tissue defects around left femur. Chromosome
      analysis was normal. CT scan showed total absence of the quadriceps femoris
      muscle and patella. Congenital absence of the extensor mechanism and patella are
      very rare anomalies. This case differed from other patellar aplasia or dysplasia
      syndromes with the presence of fixed flexion knee contracture and aplasia of the
      extensor mechanism.

PMID- 22146564
TI  - U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus
      entry and replication.
AB  - The level of cholesterol in host cells has been shown to affect viral infection.
      However, it is still not understood why this level of regulation is important for
      successful infection. We have shown in this study that dengue virus infection was
      affected when the cholesterol intake in infected cells was disrupted using a
      cholesterol transport inhibitor, U18666A. The antiviral effect was found to
      result from two events: retarded viral trafficking in the cholesterol-loaded late
      endosomes/lysosomes and suppressed de novo sterol biosynthesis in treated
      infected cells. We also observed an additive antiviral effect of U18666A with
      C75, a fatty acid synthase inhibitor, suggesting dengue virus relies on both the
      host cholesterol and fatty acid biosynthesis for successful replication.

PMID- 22146565
TI  - Evaluation of inhaled cidofovir as postexposure prophylactic in an aerosol
      rabbitpox model.
AB  - Smallpox is considered a biological threat based upon the possibility of
      deliberate reintroduction into the population, creating an urgent need for
      effective antivirals. The antiviral drug cidofovir (Cr) has shown to be effective
      against poxviruses, although route-specific nephrotoxicity has hampered its
      development for emergency post-exposure prophylaxis (PEP). In this study, we use
      a micronized dry powder formulation of pharmaceutical-grade Cr (NanoFOVIRTM; Nf)
      to treat rabbits exposed to aerosolized rabbitpox virus (RPXV) to further
      evaluate the effectiveness of direct drug delivery to the lung. Naive rabbits
      were infected with RPXV by aerosol; three subsets received aerosolized Nf at 0.5,
      1.0 or 1.75mg/kg daily for 3days post-exposure, positive and negative control
      groups received intravenous (IV) Cr treatments and no treatment, respectively. Nf
      groups showed an antiviral-dose associated survival of 50% (0.5mg/kg), 80%
      (1.0mg/kg) and 100% (1.75mg/kg). All animals (100%) from the IV-Cr treatment
      group and none (0%) from the untreated controls survived. Nf (1.75) protected
      rabbits from RPX at approximately 10% of the equivalent IV-Cr dose. A dose
      related effect was observed in clinical development of RPX disease in Nf groups.
      Significant reduction of RPX-induced pathological changes was observed in Nf
      (1.75) and IV-Cr groups. Results suggest that Nf may be a viable antiviral for
      emergency post-exposure prophylaxis and should be evaluated in other models of
      poxviral disease.

PMID- 22146566
TI  - What do we know about patients' perceptions of continuity of care? A meta
      synthesis of qualitative studies.
AB  - OBJECTIVE: The increasing complexity in healthcare delivery might impede the
      achievement of continuity of care, being defined as 'one patient experiencing
      care over time as coherent and linked'. This article aims to improve the
      knowledge on patients' perceptions of relational (RC), informational (IC) and
      management continuity (MC) across care levels. DESIGN: A descriptive, qualitative
      meta-synthesis was conducted based on a literature search in various electronic
      databases using the subject heading 'continuity of care' and linked key terms. We
      scanned retrieved articles for adherence to inclusion criteria: (i) relevance to
      research topic, (ii) original study adopting a qualitative design and (iii)
      investigating the patient's perspective. Content analysis was conducted by
      identification of themes and aggregation of findings. RESULTS: The selected 25
      studies most frequently investigated RC. Being attended to regularly and over
      time by one physician (RC) was valued by chronic ill patients, but balanced with
      convenient access by young patients (MC). Communication and information transfer
      across care settings as well as the gathering of holistic information about the
      patient were perceived to foster IC. Critical features for achieving MC were
      accessibility between care levels, individualized care and a smooth discharge
      process including the receipt of support. Patients further considered that their
      personal involvement was one facilitating element of continuity of care.
      CONCLUSIONS: Patients identified elements that enhance or distract from
      continuity of care across boundaries. Variations in perceived importance seem to
      depend on both individual and contextual factors which should be taken into
      account during healthcare provision.

PMID- 22146567
TI  - Femoroacetabular impingement in a high school female athlete.
AB  - The patient was a 17-year-old female who was referred to a physical therapist by
      her primary-care physician with a chief complaint of bilateral hip and groin
      pain. The patient was treated by the physical therapist for 8 weeks, but she was
      unable to successfully return to playing soccer. The patient was subsequently
      referred to an orthopaedic surgeon, who ordered a magnetic resonance arthrogram
      that did not reveal intra-articular pathology. To further evaluate bony
      morphology, computed tomography with 3-dimensional reconstructions was ordered,
      which demonstrated findings consistent with cam-type femoroacetabular
      impingement.

PMID- 22146568
TI  - Anomalies in the ion transport of phosphoric acid in water and heavy-water
      environments.
AB  - This paper presents the experimentally determined precise transport data -
      (tracer) diffusion coefficients in both water and heavy-water environments,
      together with molar conductivity and viscosity of (ortho)phosphoric acid in water
      over an extended concentration range at [Formula: see text]. The concentration
      (c) dependence of the diffusion coefficients (D), viscosity [Formula: see text]
      and molar conductivity [Formula: see text] have been analysed. An anomalous
      depression in the D - [Formula: see text] curve for both [Formula: see text] -
      [Formula: see text] and [Formula: see text] - [Formula: see text] systems in the
      neighbourhood of 0.8 M is observed, which is complementary to the sudden sharp
      rise observed in the [Formula: see text] curve in the neighbourhood of 0.8 M.
      Although the occurrence of such an anomaly could be inferred from the earlier
      conductance, e.m.f. and diffusion data, it was never conclusively inferred
      earlier. This new set of diffusion and viscosity data clearly delineates
      anomalies in the ion transport of phosphoric acid.

PMID- 22146569
TI  - Endoplasmic reticulum stress is activated in endometrial adenocarcinoma.
AB  - OBJECTIVES: Endometrial cancer is the most common malignancy of the female
      genital tract. However, in spite of a huge advance in our understanding of
      endometrial cancer biology, therapeutic modalities haven't significantly changed
      over the past 40 years. The activation of the Unfolded Protein Response (UPR) and
      GRP78 increase following Endoplasmic Reticulum (ER) stress have been recently
      identified as mechanisms favoring growth, invasion and resistance to therapy of
      different types of cancer. However, a possible role of ER stress and GRP78 in
      endometrial cancer has never been investigated. METHODS: Tissue specimens from
      normal and neoplastic endometrium were analyzed for the expression of the ER
      stress markers GRP78, ATF6 and CHOP by Real-Time RT-PCR. In addition, GRP78
      protein expression and localization were evaluated by Western blot and
      immunohistochemistry, respectively. The effect of GRP78 knock down on cell growth
      of Ishikawa cells was analyzed by proliferation curve analysis. RESULTS: In this
      analysis, the expression levels of GRP78, ATF6 and CHOP mRNAs were significantly
      increased in specimens of endometrioid endometrial carcinomas. GRP78 and ATF6
      protein expression levels were also increased in specimens of endometrial
      adenocarcinomas. GRP78 knock down caused a decrease of Ishikawa cells' growth.
      CONCLUSIONS: The increased expression of ER stress markers in endometrioid
      endometrial carcinomas suggests a role for ER stress, the UPR and, possibly,
      GRP78 in endometrial cancer. Whether these mechanisms have a substantial function
      in the pathogenesis of malignant transformation of human endometrium is still
      under investigation in our laboratory.

PMID- 22146571
TI  - Dural venous sinus angioplasty and stenting for the treatment of idiopathic
      intracranial hypertension.
AB  - BACKGROUND: Lumboperitoneal shunt (LPS), ventriculoperitoneal shunt (VPS) and
      optic nerve sheath fenestration (ONSF) are accepted surgical therapies for
      medically refractory idiopathic intracranial hypertension (IIH). In the subset of
      patients with IIH and venous sinus stenosis, dural venous sinus stenting has
      emerged as an alternative surgical approach. METHODS: All cases of dural stents
      for IIH at our institution were retrospectively reviewed. Eligibility criteria
      included medically refractory IIH with documented papilledema and dural venous
      sinus stenosis of the dominant venous outflow system (gradient >=10 mm Hg).
      RESULTS: Fifteen cases (all women) of mean age 34 years were identified. All had
      failed medical therapy and six had failed surgical intervention. Technical
      success was achieved in all patients without major periprocedural complications.
      The mean preprocedural gradient across the venous stenosis was reduced from 24 mm
      Hg before the procedure to 4 mm Hg after the procedure. Headache resolved or
      improved in 10 patients. Papilledema resolved in all patients and visual acuity
      stabilized or improved in 14 patients. There were no instances of restenosis
      among the 14 patients with follow-up imaging. CONCLUSION: In this small case
      series, dural sinus stenting for IIH was performed safely with a high degree of
      technical success and with excellent clinical outcomes. These results suggest
      that angioplasty and stenting for the treatment of medically refractory IIH in
      patients with dural sinus stenosis warrants further investigation as an
      alternative to LPS, VPS and ONSF.

PMID- 22146572
TI  - CT perfusion guided delayed recanalization with favorable outcome in pediatric
      stroke.
AB  - There are no approved treatment options for acute ischemic stroke in the
      pediatric population. A case is presented of a 16-year-old boy with acute left
      sided weakness who was transferred to our institution on the third day after
      onset of symptoms and after deterioration in his condition. He had right internal
      carotid artery occlusion beyond the origin of the ophthalmic artery. CT perfusion
      study showed a large area of penumbra in the right middle cerebral artery
      distribution. Recanalization was achieved with self-expanding stent placement and
      mechanical thrombectomy. Post procedure CT perfusion study showed resolution of
      the penumbra. At the 3 month follow-up, his modified Rankin Scale score was 1 and
      at 1 year it was 0. A subset of pediatric patients with acute ischemic stroke
      secondary to large intracranial arterial occlusion may be potential candidates
      for this treatment approach.

PMID- 22146573
TI  - Mechanical thrombectomy as first-line treatment for venous sinus thrombosis:
      technical considerations and preliminary results using the AngioJet device.
AB  - BACKGROUND: Cerebral venous sinus thrombosis (CVT) is an uncommon cause of stroke
      that is usually treated medically with intravenous heparin therapy followed by
      long-term anticoagulation therapy. A series of patients with CVT who underwent
      rheolytic thrombectomy with the AngioJet as a first-line adjunctive treatment in
      addition to standard anticoagulation therapy is presented. METHODS: Prospectively
      maintained endovascular databases at two institutions were retrospectively
      reviewed. The available clinical and imaging data were compiled at each
      institution and combined for analysis. RESULTS: Over 18 months, 13 patients
      (seven women and six men; age range 17-73 years, median age 45 years) with CVT
      were treated with rheolytic thrombectomy. Immediate (partial or complete)
      recanalization of the thrombosed intracranial sinuses was achieved in all
      patients. At a median radiographic follow-up of 7 months there was continued
      patency of all recanalized sinuses. Clinical follow-up was available on nine
      patients: modified Rankin score of 0 in four patients, 1 in three patients and 6
      in two patients. CONCLUSION: This series demonstrates the feasibility of
      performing mechanical thrombectomy as a first-line treatment for acute CVT. This
      technique facilitates the prompt restoration of intracranial venous outflow,
      which may result in rapid neurological and symptomatic improvement.

PMID- 22146574
TI  - Stenting of complete vertebral artery ostial occlusion in a patient with
      medically refractory vertebrobasilar ischemia.
AB  - The case history is described of a man in his late 50s who presented with
      recurrent vertebrobasilar ischemic events despite maximal medical treatment in
      the setting of a complete left vertebral artery ostial occlusion. The complete
      occlusion was successfully treated with a drug-eluting stent. The patient has
      been symptom-free for 6 months. Stenting of vertebral artery ostial occlusion is
      technically feasible in well-selected cases.

PMID- 22146576
TI  - Mean platelet volume is increased in patients with bicuspid aortic valve.
AB  - BACKGROUND: It has been demonstrated that platelet activation occurs in patients
      with aortic stenosis. However, no study has assessed platelet activation in
      patients with a normally functioning bicuspid aortic valve (BAV). Therefore, we
      aimed to investigate relationship between platelet activation assessed by mean
      platelet volume (MPV) and normally functioning BAV. METHODS: Thirty-nine patients
      with isolated BAV and 25 age- and gender-matched healthy participants were
      included in the study. Patients with more than mild aortic regurgitation and
      aortic velocity >2 m/s were excluded from the study. For the entire study
      population, MPV was measured using an automatic blood counter. RESULTS: Compared
      to control group, MPV value was significantly higher in patients with BAV (8.6 +/
      1.0 vs 8.0 +/- 0.8, p: .01). In the correlation analysis, there was a
      significant correlation between MPV measures with aortic stiffness (r: .32 and p:
      .01) and aortic elastic modulus (r: .37 and p: .003). CONCLUSION: Our study
      results indicate that BAV is associated with elevated MPV values.

PMID- 22146575
TI  - A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation,
      inverse correlation with disease activity score and suppression of inflammatory
      cytokine and metalloproteinase release.
AB  - INTRODUCTION: The reduction of the inflammatory status represents one of the most
      important targets in rheumatoid arthritis (RA). A central role of A2A and A3
      adenosine receptors (ARs) in mechanisms of inflammation has been reported in
      different pathologies. The primary aim of this study was to investigate the A2A
      and A3ARs and their involvement in RA progression measured by Disease Activity
      Score in 28 or 44 joints (DAS28 or DAS). METHODS: ARs were analyzed by saturation
      binding assays, mRNA and Western blotting analysis in lymphocytes from early and
      established RA patients. The effect of A2A and A3AR agonists in nuclear factor kB
      (NF-kB) pathway was evaluated. Tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) release was carried out by
      A2A and A3AR activation. AR pharmacological regulation in matrix
      metalloproteinase-1 (MMP-1) and metalloproteinase-3 (MMP-3) release was also
      studied. RESULTS: In lymphocytes obtained from RA patients, A2A and A3ARs were up
      regulated if compared with healthy controls. A2A and A3AR activation inhibited
      the NF-kB pathway and diminished inflammatory cytokines such as TNF-alpha, IL
      1beta and IL-6. A2A and A3AR agonists mediated a reduction of MMP-1 and MMP-3
      release. A2A and A3AR density inversely correlated with DAS28 and DAS suggesting
      a direct role of the endogenous activation of these receptors in the control of
      RA joint inflammation. CONCLUSIONS: Taken together these data demonstrate that
      the inflammatory and clinical responses in RA are regulated by A2A and A3ARs and
      support the use of A2A and/or A3AR agonists as novel and effective
      pharmacological treatment in RA patients.

PMID- 22146577
TI  - Mean platelet volume has a prognostic value in patients with coronary artery
      ectasia.
AB  - The aim of this study was to investigate the prognostic role of mean platelet
      volume (MPV) in patients with coronary artery ectasia (CAE). The baseline MPV
      values of 258 patients with CAE were screened. The mean time of follow-up was 49
      +/- 21 months for major adverse cardiac events (MACEs) defined as the combination
      of cardiac death, nonfatal myocardial infarction (MI), rehospitalization due to
      cardiac disorders, and readmission due to chest pain. During follow-up period, 63
      (24%) MACEs developed. There were 4 (2%) cardiovascular deaths, 0 nonfatal MI, 14
      (5%) rehospitalization, and 45 (17%) readmission. Mean platelet volume values
      were significantly higher in patients with CAE with MACEs than in patients with
      CAE without MACEs (9.5 +/- 1.2 fL vs 8.9 +/- 1.1 fL, respectively, P = .002). The
      rate of MACE was higher in CAE patients with MPV of >9 fL than those with MVP of
      <=9 fL (33% vs. 15%, P = .001). Mean platelet volume has a prognostic value for
      MACEs in patients with CAE.

PMID- 22146578
TI  - Platelet function profile post-clopidogrel therapy in patients with type 2
      diabetes undergoing coronary stent implantation.
AB  - Platelet dysfunction contributes to the increased risk of thromboischemic
      complications after percutaneous coronary intervention (PCI), particularly in
      type 2 diabetes. Little is known about the effects of glycemic control on
      platelet reactivity. We assessed adenosine diphosphate-induced platelet
      aggregation and flow cytometric expression of P-selectin in 90 patients (56
      diabetic and 34 nondiabetic patients) undergoing coronary stent implantation
      after administration of clopidogrel as a potential predictor of poststent
      complications and its relation to glycemic control. Posttreatment platelet
      reactivity was significantly elevated in diabetic compared with nondiabetic
      participants and was associated with smoking, hypercholesterolemia, overweight,
      and cardiovascular ischemic events. A linear relationship was found between
      hemoglobin A1c in diabetic patients and platelet reactivity. Both methods
      (standard aggregometry and P-selectin expression) used for assessment of platelet
      function were positively correlated. Low responsiveness to clopidogrel detected
      by posttreatment platelet reactivity is a risk factor for ischemic events after
      PCI in diabetic patients.

PMID- 22146579
TI  - Differential responses of primary auditory cortex in autistic spectrum disorder
      with auditory hypersensitivity.
AB  - The aim of this study was to investigate the differential responses of the
      primary auditory cortex to auditory stimuli in autistic spectrum disorder with or
      without auditory hypersensitivity. Auditory-evoked field values were obtained
      from 18 boys (nine with and nine without auditory hypersensitivity) with autistic
      spectrum disorder and 12 age-matched controls. Autistic disorder with
      hypersensitivity showed significantly more delayed M50/M100 peak latencies than
      autistic disorder without hypersensitivity or the control. M50 dipole moments in
      the hypersensitivity group were larger than those in the other two groups
      [corrected]. M50/M100 peak latencies were correlated with the severity of
      auditory hypersensitivity; furthermore, severe hypersensitivity induced more
      behavioral problems. This study indicates auditory hypersensitivity in autistic
      spectrum disorder as a characteristic response of the primary auditory cortex,
      possibly resulting from neurological immaturity or functional abnormalities in
      it.

PMID- 22146580
TI  - Reduced prefrontal hemodynamic response in children with ADHD during the Go/NoGo
      task:  a NIRS study.
AB  - The current study examined the hemodynamic response during the Go/NoGo task in
      children with/without attention deficit/hyperactivity disorder (ADHD). Using near
      infrared spectroscopy, oxy-Hb and deoxy-Hb concentration changes in the frontal
      areas were compared during the conditions with/without inhibitory demand.
      Compared with typically developing children, children with ADHD showed
      significantly reduced activation during the conditions with inhibitory demand
      (NoGo-condition) in the frontal areas. However, no significant differences in
      activation during the conditions without inhibitory demand (Go-condition) were
      found between the two groups. The current findings revealed that children with
      ADHD exhibit an altered hemodynamic response specifically during response
      inhibition, but not during response execution, and suggested the clinical
      usefulness of near-infrared spectroscopy for the evaluation of response
      inhibition deficits in children with ADHD.

PMID- 22146581
TI  - Chrysalis and negative pigment network in Spitz nevi.
AB  - Chrysalis, also named shiny white streaks, are white, linear structures only
      visible with polarized dermoscopy. They have been reported in several tumors
      included melanomas and Spitz nevi, and their histological substrate is believed
      to be dermal fibrosis. We have performed a correlation study between the
      dermoscopic and the histopathological features of 9 Spitz nevi. Chrysalis were
      present in 4 Spitz nevi (44%) and in all of them there was a high degree of
      fibroplasia. In one case, chrysalis, evident at the center of the lesion,
      progressively merged with negative pigment network at the periphery. We suggest
      that chrysalis and negative pigment network are manifestations of the same
      histopathological finding: increased collagen occurring at different levels of
      the dermis.

PMID- 22146582
TI  - Carvedilol blocks the cloned cardiac Kv1.5 channels in a beta-adrenergic receptor
      independent manner.
AB  - Carvedilol, a non-selective beta-adrenergic blocker, is widely used for the
      treatment of angina pectoris and hypertension. We examined the action of
      carvedilol on cloned Kv1.5 expressed in CHO cells, using the whole-cell patch
      clamp technique. Carvedilol reduced the peak amplitude of Kv1.5 and accelerated
      the inactivation rate in a concentration-dependent manner with an IC50 of 2.56
      MUM. Using a first-order kinetics analysis, we calculated k(+1) = 19.68 MUM(-1)s(
      1) for the association rate constant, and k(-1) = 44.89 s(-1) for the
      dissociation rate constant. The apparent K(D) (k(-1)/k(+1)) was 2.28 MUM, which
      is similar to the IC50 value. Other beta-adrenergic blockers (alprenolol,
      oxprenolol and carteolol) had little or no effect on Kv1.5 currents. Carvedilol
      slowed the deactivation time course, resulting in a tail crossover phenomenon.
      Carvedilol-induced block was voltage-dependent in the voltage range for channel
      activation, but voltage-independent in the voltage range for full activation. The
      voltage dependences for both steady-state activation and inactivation were
      unchanged by carvedilol. Carvedilol affected Kv1.5 in a use-dependent manner.
      When stimulation frequencies were increased to quantify a use-dependent block,
      however, the block by carvedilol was slightly increased with IC50 values of 2.56
      MUM at 0.1 Hz, 2.38 MUM at 1 Hz and 2.03 MUM at 2 Hz. Carvedilol also slowed the
      time course of recovery from inactivation of Kv1.5. These results indicate that
      carvedilol blocks Kv1.5 in a reversible, concentration-, voltage-, time-, and use
      dependent manner, but only at concentrations slightly higher than therapeutic
      plasma concentrations in humans. These effects are probably relevant to an
      understanding of the ionic mechanism underlying the antiarrhythmic property of
      carvedilol.

PMID- 22146583
TI  - The molecular pharmacology of AMD11070: an orally bioavailable CXCR4 HIV entry
      inhibitor.
AB  - In order to enter and infect human cells HIV must bind to CD4 in addition to
      either the CXCR4 or the CCR5 chemokine receptor. AMD11070 was the first orally
      available small molecule antagonist of CXCR4 to enter the clinic. Herein we
      report the molecular pharmacology of AMD11070 which is a potent inhibitor of X4
      HIV-1 replication and the gp120/CXCR4 interaction. Using the CCRF-CEM T cell line
      that endogenously expresses CXCR4 we have demonstrated that AMD11070 is an
      antagonist of SDF-1alpha ligand binding (IC50 = 12.5 +/- 1.3 nM), inhibits SDF-1
      mediated calcium flux (IC50 = 9.0 +/- 2.0 nM) and SDF-1alpha mediated activation
      of the CXCR4 receptor as measured by a Eu-GTP binding assay (IC50 =39.8 +/- 2.5
      nM) or a [(35)S]-GTPgammaS binding assay (IC50 =19.0 +/- 4.1 nM), and inhibits
      SDF-1alpha stimulated chemotaxis (IC50 =19.0 +/- 4.0 nM). AMD11070 does not
      inhibit calcium flux of cells expressing CXCR3, CCR1, CCR2b, CCR4, CCR5 or CCR7,
      or ligand binding to CXCR7 and BLT1, demonstrating selectivity for CXCR4. In
      addition AMD11070 is able to inhibit the SDF-1beta isoform interactions with
      CXCR4; and N-terminal truncated variants of CXCR4 with equal potency to wild type
      receptor. Further mechanistic studies indicate that AMD11070 is an allosteric
      inhibitor of CXCR4.

PMID- 22146584
TI  - Thiadiazolidinones: a new class of alanine racemase inhibitors with antimicrobial
      activity against methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a human pathogen and a
      major cause of hospital-acquired infections. New antibacterial agents that have
      not been compromised by bacterial resistance are needed to treat MRSA-related
      infections. We chose the S. aureus cell wall synthesis enzyme, alanine racemase
      (Alr) as the target for a high-throughput screening effort to obtain novel enzyme
      inhibitors, which inhibit bacterial growth. Among the 'hits' identified was a
      thiadiazolidinone with chemical properties attractive for lead development. This
      study evaluated the mode of action, antimicrobial activities, and mammalian cell
      cytotoxicity of the thiadiazolidinone family in order to assess its potential for
      development as a therapeutic agent against MRSA. The thiadiazolidones inhibited
      Alr activity with 50% inhibitory concentrations (IC50) ranging from 0.36 to 6.4
      MUM, and they appear to inhibit the enzyme irreversibly. The series inhibited the
      growth of S. aureus, including MRSA strains, with minimal inhibitory
      concentrations (MICs) ranging from 6.25 to 100 MUg/ml. The antimicrobial activity
      showed selectivity against Gram-positive bacteria and fungi, but not Gram
      negative bacteria. The series inhibited human HeLa cell proliferation. Lead
      development centering on the thiadiazolidinone series would require additional
      medicinal chemistry efforts to enhance the antibacterial activity and minimize
      mammalian cell toxicity.

PMID- 22146585
TI  - Modulation of AT-1R/AMPK-MAPK cascade plays crucial role for the pathogenesis of
      diabetic cardiomyopathy in transgenic type 2 diabetic (Spontaneous Diabetic
      Torii) rats.
AB  - There are evidences that the activation of AMPK is playing pivotal role in the
      lipid and glucose metabolism. It has been reported that both the AMPK and
      angiotensin-II acts as a negative regulator for each protein. It has been well
      proven that the MAPK cascade could be modulated by the presence of angiotensin
      II. Moreover, studies were shown that p38 MAPK stimulates glucose uptake through
      the AMPK activation. Therefore, we speculate and tried to demonstrate that the
      modulation of AT-R/MAPK pathway through AMPK might play crucial roles for the
      pathogenesis of diabetic cardiomyopathy, using the transgenic (Spontaneous
      Diabetic Torii-SDT) rats. We performed Western blot analysis for the measurement
      of myocardial AT-R, AMPK and MAPK cascades-related protein expressions, p67-phox
      and caspase-12. In addition, we employed dihydroethidium (DHE), Azan Mallory and
      hemotoxylin eosin (HE) staining methods to demonstrate the superoxide radical
      production, fibrosis and hypertrophy, respectively. The protein expressions, such
      as AT-1R, p-ERK1/2, p67-phox and caspase-12 were found to be significantly
      increased and conversely, the Ang-(1-7) mas R, Tak1, LKB1 and p-AMPKalpha1, p-p38
      MAPK and p-JNK protein expressions were found to be considerably decreased in the
      SDT rats, in comparison to the normal rats. The DHE, Azan Mallory and HE
      stainings also revealed that the SDT rats have more superoxide radical
      production, fibrosis and hypertrophy, respectively than the normal rats. Taken
      together, it is suggested that the modulation of AT-1R/AMPK-MAPK pathway might
      play crucial roles for the pathogenesis of diabetic cardiomyopathy and it could
      become an important therapeutic target to ameliorate the diabetic cardiomyopathy.

PMID- 22146586
TI  - Normobaric hyperoxia protects the blood brain barrier through inhibiting Nox2
      containing NADPH oxidase in ischemic stroke.
AB  - Normobaric hyperoxia (NBO) has been shown to be neuro- and vaso-protective
      during ischemic stroke. However, the underlying mechanisms remain to be fully
      elucidated. Activation of NADPH oxidase critically contributes to ischemic brain
      damage via increase in ROS production. We herein tested the hypothesis that NBO
      protects the blood-brain barrier (BBB) via inhibiting gp91phox (or called Nox2)
      containing NADPH oxidase in a mouse model of middle cerebral artery occlusion
      (MCAO). Wild-type C57/BL6 mice and gp91phoxknockout mice were given NBO (95% O2)
      or normoxia (21% O2) during 90-min MCAO, followed by 22.5 hrs of reperfusion. BBB
      damage was quantified by measuring Evans blue extravasation. The protein levels
      of matrix metalloproteinase-9 (MMP-9), tight junction protein occludin and
      gp91phox were assessed with western blot. Gel zymography was used to assess the
      gelatinolytic activity of MMP-9. In the wild type mice, cerebral ischemia and
      reperfusion led to remarkable Evans blue extravasation, significantly increased
      gp91phox and MMP-9 levels and decreased occludin levels in the ischemic brain
      tissue. In gp91phox knockout mice, the changes in Evans blue extravasation, MMP-9
      and occludin were at much smaller magnitudes when compared to the wild type.
      Importantly, NBO treatment significantly reduced the changes in all measured
      parameters in wild type mice, while did not cause additional reductions in these
      changes when gp91phox was knocked out. These results indicate that activation of
      Nox2 containing NADPH oxidase is implicated in the induction of MMP-9, loss of
      occludin and BBB disruption in ischemic stroke, and inhibition of Nox2 may be an
      important mechanism underlying NBO-afforded BBB protection.

PMID- 22146587
TI  - Adaptation of Rhodococcus erythropolis cells for growth and bioremediation under
      extreme conditions.
AB  - Bioremediation of contaminated sites is rarely performed in nature under ideal
      growth conditions for bacteria. Extremophiles can grow at extreme values of
      temperature, pH, ionic strength and metal concentrations, but it may be difficult
      to find and isolate those possessing the required metabolic activities. In the
      present work, Rhodococcus erythropolis, a bacterium known to possess a large
      number of catabolic activities, was adapted to grow at 4-37 degrees C, pH 3-11
      and in the presence of up to 7.5% sodium chloride and 1% copper sulfate. The
      large majority of adapted cells were able to maintain polarization of the
      membrane under the most difficult conditions tested and to adjust the net surface
      charge. The cells changed the composition of fatty acids of the cellular membrane
      according to conditions endured. Changes in the relative proportion of straight,
      methyl and cyclopropyl saturated, unsaturated and hydroxyl substituted fatty
      acids were observed, as well as production of polyunsaturated fatty acids unusual
      in bacteria. The adapted R. erythropolis cells were able to degrade C6-C16 n
      alkanes and alcohols under the previously considered extreme conditions for this
      bacterium.

PMID- 22146588
TI  - Response of leaf-associated bacterial communities to primary acyl-homoserine
      lactone in the tobacco phyllosphere.
AB  - The phyllosphere is inhabited by large populations of epiphytic bacteria that are
      able to modulate their phenotypes and behavior by quorum sensing (QS). However,
      the impact of acyl-homoserine lactones (AHLs) involved in QS on the ecology of
      bacteria in their natural habitat remains unclear. Therefore, we used a bioassay
      and liquid chromatography-mass spectrometry to detect AHLs in the tobacco
      phyllosphere. Our results identified several AHLs in the tobacco phyllosphere,
      the majority of which were short-chain AHLs. Furthermore, the addition of an
      exogenous N-(3-oxohexanoyl) homoserine lactone (3OC6HSL), which is seen in the
      naturally occurring tobacco phyllosphere, generated variability in the
      composition of the bacterial community as determined by denaturing gradient gel
      electrophoresis (DGGE) analysis and phospholipid fatty acid (PLFA) analysis.
      Notably, the ratio of Gram-positive (GP) bacteria increased in response to
      treatment with 1 MUM AHL, but decreased incipiently when treated with 10 MUM AHL.
      These observations provide insight into the composition of the leaf-colonizing
      epiphyte community responsible for AHLs, particularly GP bacteria as they do not
      use AHLs as signaling molecules for QS.

PMID- 22146589
TI  - The electronic structure of liquid silver chalcogenides: a tight-binding
      approach.
AB  - We present a computational study of the electronic structure of the
      stoichiometric liquid zero-gap semiconductors [Formula: see text], [Formula: see
      text] and [Formula: see text]. The geometry of the fluids is described by the
      primitive model of charged hard spheres; the electronic structure is modelled
      using a tight-binding Hamiltonian. The density of states is computed considering
      the Madelung potential fluctuations and the topological disorder characteristic
      of an ionic fluid. Only the introduction of nonzero tight-binding hopping matrix
      elements - equivalent to the formation of chemical bonds - induces a pseudogap
      between the chalcogenide conduction band and the silver valence band. The Fermi
      level can be located in a region of a small density of states; eigenstates at
      [Formula: see text] are likely to exhibit disorder-induced localization.

PMID- 22146590
TI  - Early prognostic factors in patients with whiplash.

PMID- 22146591
TI  - BAG2 is a target of the c-Myc gene and is involved in cellular senescence via the
      p21(CIP1) pathway.
AB  - Suppression of c-Myc is likely to induce cellular senescence in many tumors with
      unclear mechanisms. A proteomics survey indicated that high levels of BCL2
      associated athanogene 2 (BAG2) were found in response to c-Myc repression in
      TRE293 cells. This observation led to the investigation into the role of BAG2 in
      c-Myc-induced senescence. The association of the c-Myc/SP1 complex with the BAG2
      promoter verified the role of c-Myc/SP1 in regulating BAG2 transcription.
      Furthermore, high levels of BAG2 were found to induce p21(CIP1)-dependent
      senescence and subsequent carcinogenetic arrest, suggesting its possible role as
      an indirect activator of the p21(CIP1) pathway.

PMID- 22146592
TI  - Histamine promotes rat motor performances by activation of H(2) receptors in the
      cerebellar fastigial nucleus.
AB  - The cerebellar fastigial nucleus (FN), together with the interpositus nucleus
      (IN), constitutes the two final output nuclei of the spinocerebellum and plays an
      important role in body and limb movements. Previous studies have revealed a
      direct histaminergic projection from the hypothalamus to the cerebellar nuclei
      and an excitatory effect of histamine on the IN neurons. However, role of
      hypothalamic histaminergic projection in the FN has been still little known. Here
      we show that histamine elicited the FN neurons of rats a concentration-dependent
      excitatory response in vitro. The histamine-induced excitation on FN neurons was
      mediated by postsynaptic histamine H2 rather than H1 receptors. In behavioral
      tests, microinjection of histamine into bilateral FNs remarkably improved motor
      performances of rats on both accelerating rota-rod and balance beam. Selective H2
      receptor antagonist ranitidine considerably declined those motor performances and
      selective H2 receptor agonist dimaprit mimicked the facilitation effect of
      histamine on the movements. But selective H1 receptor antagonist triprolidine and
      agonist 2-pyridylethylamine had no effect. Furthermore, microinjection of
      histamine into bilateral FNs narrowed stride width of footprint but did not
      influence wire suspension, whereas microinjection of histamine into bilateral INs
      increased stride length and promoted suspension. These results demonstrate that
      histamine enhances rat motor balance and coordination through modulation of both
      proximal and distal muscles by activation of histamine H2 receptors in the
      cerebellar FN and IN, and suggest that the hypothalamocerebellar histaminergic
      projections may modulate the final outputs of the spinocerebellum and participate
      in the cerebellum-mediated motor control.

PMID- 22146593
TI  - Unilateral nigrostriatal 6-hydroxydopamine lesions in mice I: motor impairments
      identify extent of dopamine depletion at three different lesion sites.
AB  - The unilateral 6-hydroxydopamine mouse lesion models of Parkinson's disease have
      received increasing attention in recent years, but comparison of the different
      lesion models was largely focused at a histological level. An extensive
      behavioural comparison between different mouse models on tests of motor function
      has yet to be carried out, to pin point tests that accurately discriminate
      between different extents of dopaminergic depletion. In the present study we
      examine the consequences of injection of the toxin at three sites along the
      nigrostriatal tract (substantia nigra, medial forebrain bundle, and striatum) on
      a broad range of simple motor tasks, and on the dopaminergic pathology. All
      lesion groups demonstrated marked behavioural deficits and displayed distinct
      profiles of degeneration along the nigrostriatal dopamine pathway. Tests that
      correlated closely with the level of substantia nigra cell loss included the
      corridor, cylinder and balance beam tests, the rotarod, inverted cage lid and
      three types of rotational assessment (spontaneous, amphetamine-induced and
      apomorphine-induced). Specific tasks are identified which are capable of
      distinguishing a near-complete lesion, with amphetamine rotation, corridor and
      cylinder tests showing the highest correlations with levels of nigral cell loss.
      Performance in the different behavioural tests was associated with distinct
      profiles of cell loss in the SN and VTA. We provide a comprehensive behavioural
      assessment of lesion-induced deficits in mouse models of PD, which should
      facilitate selection of the most appropriate lesion model and most sensitive
      behavioural tests for use in future studies investigating therapeutic
      interventions.

PMID- 22146594
TI  - sQUIZ your knowledge! A holiday souvenir. Myasis.

PMID- 22146595
TI  - Hypoxia imaging with PET:  which tracers and why?

PMID- 22146596
TI  - Estimating intercellular surface tension by laser-induced cell fusion.
AB  - Intercellular surface tension is a key variable in understanding cellular
      mechanics. However, conventional methods are not well suited for measuring the
      absolute magnitude of intercellular surface tension because these methods require
      determination of the effective viscosity of the whole cell, a quantity that is
      difficult to measure. In this study, we present a novel method for estimating the
      intercellular surface tension at single-cell resolution. This method exploits the
      cytoplasmic flow that accompanies laser-induced cell fusion when the pressure
      difference between cells is large. Because the cytoplasmic viscosity can be
      measured using well-established technology, this method can be used to estimate
      the absolute magnitudes of tension. We applied this method to two-cell-stage
      embryos of the nematode Caenorhabditis elegans and estimated the intercellular
      surface tension to be in the 30-90 uN m(-1) range. Our estimate was in close
      agreement with cell-medium surface tensions measured at single-cell resolution.

PMID- 22146597
TI  - Autoantibody signatures as biomarkers to distinguish prostate cancer from benign
      prostatic hyperplasia in patients with increased serum prostate specific antigen.
AB  - BACKGROUND: Serum prostate specific antigen (PSA) concentrations lack the
      specificity to differentiate prostate cancer from benign prostate hyperplasia
      (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures
      to specific cancer targets which might be able to differentiate prostate cancer
      from BPH in patients with increased serum PSA. METHODS: To identify autoantibody
      signatures as biomarkers, a native antigen reverse capture microarray platform
      was used. Briefly, well-characterized monoclonal antibodies were arrayed onto
      nanoparticle slides to capture native antigens from prostate cancer cells.
      Prostate cancer patient serum samples (n=41) and BPH patient samples (collected
      starting at the time of initial diagnosis) with a mean follow-up of 6.56 y
      without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of
      IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The
      arrays were scanned for fluorescence and the intensity was quantified. Receiver
      operating characteristic curves were produced and the area under the curve (AUC)
      was determined. RESULTS: Using our microarray platform, we identified
      autoantibody signatures capable of distinguishing between prostate cancer and
      BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and
      CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95%
      at 80% specificity) compared to AUC of 0.5 for serum concentration PSA
      (sensitivity of 12.2% at 80% specificity). CONCLUSION: Our preliminary results
      showed that we were able to identify specific autoantibody signatures that can
      differentiate prostate cancer from BPH, and may result in the reduction of
      unnecessary biopsies in patients with increased serum PSA.

PMID- 22146598
TI  - Apelin in acute myocardial infarction and heart failure induced by ischemia.
AB  - Apelin is a recently isolated novel endogenous ligand for the angiotensin-like 1
      receptor (APJ). Initial experiments in animal models indicate that the
      cardiovascular system is the main target of the apelin-APJ system. Apelin plays
      an opposite role to the renin-angiotensin-aldosterone system as a compensatory
      mechanism. It is reduced in patients with heart failure, also of ischemic origin.
      However, only animal studies concern the role of the apelin-APJ system in
      myocardial ischemia. Less is known about the function of this adipokine in an
      acute phase of myocardial infarction in human. The apelin-APJ system could
      perhaps be involved in myocardial protection during acute myocardial ischemia. In
      the current review we have summarized recent data concerning the role of apelin
      in acute myocardial infarction and heart failure induced by ischemia.

PMID- 22146599
TI  - Serum levels of IgG4 and soluble interleukin-2 receptor in patients with coronary
      artery disease.
AB  - BACKGROUND: Immunoglobulin G4 (IgG4)-related immuno-inflammation has been
      suggested to play a role in the development of remodeling of arterial wall. We
      investigated the association between serum concentrations of IgG4 or soluble
      interleukin-2 receptor (sIL-2R) and coronary artery disease (CAD). METHODS: Serum
      concentrations of IgG4 and sIL-2R were measured in 286 patients who underwent
      coronary angiography. RESULTS: In patients with CAD, the medians of serum
      concentrations of IgG4 (39.3 mg/dl) and sIL-2R (388 U/ml) were significantly
      higher than corresponding values in patients without CAD (IgG4 27.0 mg/dl, sIL-2R
      312 U/ml). In receiver-operating characteristic curve analysis, the area under
      the curve of sIL-2R and IgG4 for the presence of CAD was 0.634 and 0.632,
      respectively. Age- and gender-adjusted logistic regression analysis showed that
      both of the fourth quartile of sIL-2R concentrations (>=509 U/ml) and that of
      IgG4 concentrations (>=57.7 mg/dl) were found to be associated with CAD with an
      odds ratio of 2.82 and 4.08, respectively, compared with the corresponding lowest
      quartile. CONCLUSIONS: Serum concentrations of IgG4 and sIL-2R were increased in
      patients with angiographically-proven CAD, suggesting that IgG4-related immuno
      inflammation may also have a role in the development and/or progression of
      coronary artery atherosclerosis.

PMID- 22146601
TI  - Year in review 2010: Critical Care--Multiple organ dysfunction and sepsis.
AB  - This review summarizes new insights in the pathophysiologic implications of
      inflammation and microvascular alterations in organ dysfunction, as well as
      genetic factor contribution, from clinical and experimental studies that were
      published in 2010 in Critical Care in the fields of multiple organ dysfunction
      and sepsis. New diagnostic and prognostic markers of organ dysfunction are
      presented. Evaluations of novel therapeutic strategies, including implementation
      of international guidelines, modulation of inflammation and coagulation, and
      prevention of ventilator-induced lung injury and acute kidney injury, are
      reported. The results of these experimental studies and clinical trials are
      discussed in the context of the current relevant scientific and clinical
      background.

PMID- 22146602
TI  - Molecules, magic and forgetful fruit flies: the supernatural science of medical
      gas research.
AB  - Medical gas research often involves the study of molecules under
      extraphysiologic conditions, that is, conditions that do not exist in nature.
      This "supernatural" nature of medical gas research sometimes produces results
      that appear to be almost "magic" to those schooled in traditional physiology"Any
      sufficiently advanced technology is indistinguishable from magic".-Arthur C.
      Clarke.

PMID- 22146603
TI  - The multiple sclerosis work difficulties questionnaire.
AB  - BACKGROUND: A better understanding of the workplace difficulties experienced by
      people with multiple sclerosis (PwMS) may be critical to developing appropriate
      vocational and rehabilitative programs. OBJECTIVE: We aimed to assess the factor
      structure, internal consistency and validity of the new Multiple Sclerosis Work
      Difficulties Questionnaire (MSWDQ). METHODS: Work difficulty items were developed
      and reviewed by a panel of experts. Using the MSWDQ, cross-sectional self-report
      data of work difficulties were obtained in addition to employment status and MS
      disease information, in a community-based sample of 189 PwMS. RESULTS:
      Exploratory Maximum Likelihood Factor Analysis on the draft questionnaire yielded
      50 items measuring 12 factors. Subscale internal consistencies ranged from 0.74
      to 0.92, indicating adequate to excellent internal consistency reliability. The
      MSWDQ explained 40% of the variance in reduced work hours since diagnosis, 40% of
      the variance in expectations about withdrawing from work, 34% of the variance in
      expectations about reducing work hours, and 39% of the variance in expectations
      about changing type of work due to MS. CONCLUSION: The MSWDQ is a valid and
      internally reliable measure of workplace difficulties in PwMS. Physical
      difficulties, as well as cognitive and psychological difficulties were important
      predictors of workplace outcomes and expectations about future employment.

PMID- 22146604
TI  - The emerging relationship between neuromyelitis optica and systemic rheumatologic
      autoimmune disease.
AB  - Neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) are associated with
      autoantibodies that target aquaporin-4 and, in many cases, multiple other
      autoantibodies, including antinuclear antibody and antibodies to extractable
      nuclear antigens. The clinical syndromes that define NMO and NMOSD, especially
      longitudinally extensive transverse myelitis and optic neuritis, can also occur
      in the context of established rheumatologic diseases such as systemic lupus
      erythematosus and Sjogren syndrome and other organ-specific autoimmune diseases.
      These observations raise questions fundamental to both clinical practice and
      etiologic research. For example, they could suggest that NMO is one manifestation
      of a genetic tendency toward humoral autoimmunity. Alternatively, they might
      indicate that NMO is a central nervous system complication of a multisystem
      rheumatologic disease. We describe the historical background of this controversy,
      summarize the current evidence that addresses NMO-systemic autoimmunity
      relationships, and discuss the practical implications for clinical management.

PMID- 22146605
TI  - Development of extensive brain lesions following fingolimod (FTY720) treatment in
      a patient with neuromyelitis optica spectrum disorder.
AB  - We report the case of a patient who developed extensive brain lesions during
      fingolimod (FTY720) treatment in the TRANSFORMS study. His initial diagnosis was
      multiple sclerosis, but after encephalopathy anti-aquaporin4 antibody (anti-AQP4
      Ab) was detected, it was changed to neuromyelitis optica spectrum disorder. After
      treatment with fingolimod, he developed bilateral extensive brain lesions. The
      brain MRI showed lesions predominantly involving the right frontal and parietal
      lobes, with vasogenic edema and enhancement. He had residual encephalomalacia and
      no recurrence with steroid treatment over 3 years following withdrawal of
      fingolimod.

PMID- 22146606
TI  - Truly benign multiple sclerosis is rare: let's stop fooling ourselves-
      commentary.

PMID- 22146607
TI  - Truly benign multiple sclerosis is rare: let's stop fooling ourselves--yes.

PMID- 22146608
TI  - Truly benign multiple sclerosis is rare: let's stop fooling ourselves--no.

PMID- 22146609
TI  - Robot-assisted gait training in multiple sclerosis patients: a randomized trial.
AB  - BACKGROUND: Preservation of locomotor activity in multiple sclerosis (MS)
      patients is of utmost importance. Robotic-assisted body weight-supported
      treadmill training is a promising method to improve gait functions in
      neurologically impaired patients, although its effectiveness in MS patients is
      still unknown. OBJECTIVE: To compare the effectiveness of robot-assisted gait
      training (RAGT) with that of conventional walking treatment (CWT) on gait and
      generalized functions in a group of stable MS patients. METHODS: A prospective
      randomized controlled trial of 12 sessions of RAGT or CWT in MS patients of EDSS
      score 5-7. Primary outcome measures were gait parameters and the secondary
      outcomes were functional and quality of life parameters. All tests were performed
      at baseline, 3 and 6 months post-treatment by a blinded rater. RESULTS: Fifteen
      and 17 patients were randomly allocated to RAGT and CWT, respectively. Both
      groups were comparable at baseline in all parameters. As compared with baseline,
      although some gait parameters improved significantly following the treatment at
      each time point there was no difference between the groups. Both FIM and EDSS
      scores improved significantly post-treatment with no difference between the
      groups. At 6 months, most gait and functional parameters had returned to
      baseline. CONCLUSIONS: Robot-assisted gait training is feasible and safe and may
      be an effective additional therapeutic option in MS patients with severe walking
      disabilities.

PMID- 22146610
TI  - Consensus statement: evaluation of new and existing therapeutics for pediatric
      multiple sclerosis.
AB  - New therapies are being evaluated by clinical trials and, if efficacious,
      introduced for the treatment of adult MS. The role of these new and existing
      agents in the management of pediatric MS has yet to be defined. Pediatric
      investigation plans are now required by the Food and Drug Administration and
      European Medicines Agency for approval of new biological agents, providing an
      important opportunity to gather much-needed data for clinicians caring for
      children and adolescents with MS. However, challenges include the small number of
      patients, and the need for efficient yet comprehensive study designs
      incorporating factors necessary to inform the clinical care of children with MS.
      The elected Steering committee of the International Pediatric MS Study Group
      (IPMSSG) conducted a structured review of existing data on the disease-modifying
      therapies in pediatric MS and developed a consensus statement, which was further
      modified by the IPMSSG general membership, using an online survey tool. Fifty-one
      IPMSSG members from 21 countries responded to the survey, and 50 approved the
      final statement. Consensus recommendations regarding use of existing first- and
      second-line therapies, as well as a proposed definition for inadequate treatment
      response, are presented. Recommendations for the use and evaluation of emerging
      therapies (currently in phase III clinical trials or recently approved for adult
      MS) are discussed. The IPMSSG endorses the inclusion of pediatric MS patients in
      trials evaluating appropriate new and emerging therapies. Mechanisms for
      conducting high-impact, multicenter studies, including long-term follow-up in
      pediatric MS, are required to ensure that all MS patients, irrespective of age,
      benefit from advances in MS therapeutics.

PMID- 22146611
TI  - The time course and phenotype of Uhthoff phenomenon following optic neuritis.
AB  - As there is little information regarding the recovery from Uhthoff phenomenon
      (UP) in the multiple sclerosis (MS) literature, the objective of this study was
      to assess the phenotypes of UP. A one-page questionnaire was sent to 80
      consecutive optic neuritis (ON) patients seen in a tertiary neuro-ophthalmology
      clinic. Of the 48 responders to the questionnaire, 52% reported experiencing UP,
      with a range of follow-up from 1 to 20 years. Only 16% had resolution of UP, all
      this occurred within 8 weeks of the onset of ON. Of the MS patients with UP, 88%
      experienced non-visual heat-related phenomenon compared with 30% without UP. The
      presence of UP may have a more general phenotypic significance. If full recovery
      from UP has not occurred within the first 2 months from the onset of ON, then
      recovery appears to be uncommon and may therefore be a surrogate marker of
      remyelination in future drug trials.

PMID- 22146612
TI  - Multiple sclerosis and amyotrophic lateral sclerosis: is there a link?
AB  - To date, there are no reports studying the rate of amyotrophic lateral sclerosis
      (ALS) in relatives of multiple sclerosis (MS) patients and vice versa. This study
      was designed to look into this issue using two population-based databases of MS
      and ALS in Isfahan province of Iran. We have searched for any first, second or
      third degree familial kinship between the Isfahan MS Society database and Isfahan
      ALS population. We compared the rate of ALS among the population of first degree
      relatives of MS patients, with the crude prevalence of ALS in the general
      population of Isfahan. On the other hand, a reverse analysis was carried out to
      compare the prevalence of MS in Isfahan with its rate amongst the first degree
      relatives of ALS patients. We found 10 families among which five had first degree
      kinship. The rate of the diseases was significantly higher in both comparisons
      among the family members (p < 0.00001) and an odds ratios of more than 67 in both
      calculations showed a several-fold increase of ALS occurrence in the first degree
      relatives of MS patients and vice versa. In our study relatives of MS patients
      were significantly more prone to ALS and vice versa. This could give clues about
      the common features that the two disease share. Both diseases have an
      environmental and genetic component and these results mostly point toward genetic
      similarities.

PMID- 22146613
TI  - Magnetic susceptibility and electrical resistivity of dilute liquid copper - iron
      alloys.
AB  - Electrical resistivity and magnetic susceptibility measurements on dilute liquid 
      CuFe alloys are reported. Small additions of Fe increase the resistivity of
      liquid Cu in a drastic manner, whereas the temperature coefficient is found to be
      decreased. Due to the localized magnetic moments of the impurity atoms the
      diamagnetism of Cu is converted into a strong temperature-dependent paramagnetism
      indicating about 3.5 unpaired d electrons per Fe atom. The electronic properties
      of  CuFe resemble those of liquid  CuMn and  AuFe which, in the solid state, are
      known for their Kondo-like behaviour. The experimental findings are tentatively
      interpreted in terms of spin-disorder scattering with special emphasis on the
      negative temperature coefficient of the impurity resistivity.

PMID- 22146614
TI  - Barrier pressure of the oesophagogastric junction during propofol induction with
      and without alfentanil:  a double-blind, randomised, crossover study in
      volunteers.
AB  - CONTEXT: Practice varies regarding the use of opioids during rapid sequence
      induction. Controversy exists as to whether opioids may increase the risk of
      pulmonary aspiration by decreasing the barrier pressure (lower oesophageal
      sphincter-intragastric pressure). OBJECTIVES: To evaluate the effects of adding
      alfentanil during anaesthesia induction with propofol with respect to the barrier
      pressure in the oesophagogastric junction. PARTICIPANTS AND SETTING: Seventeen
      healthy volunteers (11 men and six women) participated in a double-blind,
      randomised, crossover trial at the University Hospital in Orebro, Sweden.
      INTERVENTIONS AND OUTCOME MEASURES: The volunteers were anaesthetised on two
      different occasions, randomly assigned to receive either alfentanil 20 MUg kg(-1)
      or an equivalent amount of isotonic saline, administered intravenously, 1 min
      before induction with propofol 2 mg kg(-1). One minute after propofol
      administration, a cricoid pressure of 30 N was applied. The primary outcome was
      the difference in the change in barrier pressure between the alfentanil and the
      placebo occasion 1 min after propofol administration. The secondary outcomes were
      differences in the changes in barrier pressure 1 min after alfentanil or placebo
      administration and during ongoing cricoid pressure application. RESULTS: There
      were no statistically significant differences in barrier pressure, at any time
      point, between anaesthesia induction with alfentanil and propofol compared with
      induction with placebo and propofol. The barrier pressure never decreased to less
      than 2.4 mmHg in any volunteer. CONCLUSION: Our study showed no increased risk
      regarding the integrity of the gastro-oesophageal junction when alfentanil is
      added during an induction with propofol in volunteers. This supports the practice
      of adding opioids as adjuvants during rapid sequence induction.

PMID- 22146615
TI  - Performance of tracheal intubation with the SensaScope in severe difficult
      airway.

PMID- 22146616
TI  - The mouse as a model to investigate sex steroid metabolism in the normal and
      pathological prostate.
AB  - Metabolism of sex steroids within the prostate is an important factor affecting
      its growth and pathology. Mouse models with genetic gain- and especially loss-of
      function have characterised different steroid metabolic pathways and their
      contribution to prostate pathology. With reference to the human prostate, this
      review aims to summarize the steroidogenic pathways in the mouse prostate as the
      basis for using the mouse as a model for intraprostatic steroid signalling. In
      this review we summarize the current information for three main components of the
      steroid signalling pathway in the mouse prostate: circulating steroids, steroid
      receptors and steroidogenic enzymes with regard to signalling via androgen,
      estrogen, progesterone and glucocorticoid pathways. This review reveals many
      opportunities for characterisation steroid metabolism in various mouse models.
      The knowledge of steroid metabolism within prostate tissue and in a lobe
      (rodent)/region (human) specific manner, will give valuable information for
      future, novel hypotheses of intraprostatic control of steroid actions. This
      review summarizes knowledge of steroid metabolism in the mouse prostate and its
      relevance to the human.

PMID- 22146617
TI  - High-dose chemotherapy with autologous stem cell transplant for breast cancer:
      what have we learned 25 years later?

PMID- 22146618
TI  - Effect of cellulose physical characteristics, especially the water sorption
      value, on the efficiency of its hydrolysis catalyzed by free or immobilized
      cellulase.
AB  - Cellulase, an enzymatic complex that synergically promotes the degradation of
      cellulose to glucose and cellobiose, free or adsorbed onto Si/SiO(2) wafers at 60
      degrees C has been employed as catalyst in the hydrolysis of microcrystalline
      cellulose (Avicel), microcrystalline cellulose pre-treated with hot phosphoric
      acid (CP), cotton cellulose (CC) and eucalyptus cellulose (EC). The physical
      characteristics such as index of crystallinity (I(C)), degree of polymerization
      (DP) and water sorption values were determined for all samples. The largest
      conversion rates of cellulose into the above-mentioned products using free
      cellulase were observed for samples with the largest water sorption values;
      conversion rates showed no correlation with either I(C) or DP of the biopolymer.
      Cellulose with large water sorption value possesses large pore volumes, hence
      higher accessibility. The catalytic efficiency of immobilized cellulase could not
      be correlated with the physical characteristics of cellulose samples. The
      hydrolysis rates of the same cellulose samples with immobilized cellulase were
      lower than those by the free enzyme, due to the diffusion barrier (biopolymer
      chains approaching to the immobilized enzyme) and less effective contact between
      the enzyme active site and its substrate. Immobilized cellulase, unlike its free
      counterpart, can be recycled at least six times without loss of catalytic
      activity, leading to higher overall cellulose conversion.

PMID- 22146619
TI  - Relationship between pancreaticobiliary maljunction and gallbladder carcinoma:
      meta-analysis.
AB  - BACKGROUND: Reports on the relationship between pancreaticobiliary maljunction
      (PBM) and gallbladder carcinoma (GBC) are conflicting. The frequency of PBM in
      GBC patients and the clinical features of GBC patients with PBM vary in different
      studies. DATA SOURCES: English-language articles describing the association
      between PBM and GBC were searched in the PubMed and Web of Science databases.
      Nine case-control studies fulfilled the inclusion criteria and addressed the
      relevant clinical questions of this analysis. Data were extracted independently
      by two reviewers using a predefined spreadsheet. RESULTS: The incidence of PBM
      was higher in GBC patients than in controls (10.60% vs 1.76%, OR: 7.41, 95% CI:
      5.03 to 10.87, P<0.00001). The proportion of female patients with PBM was 1.96
      fold higher than in GBC patients without PBM (80.5% vs 62.9%, OR: 1.96, 95% CI:
      1.09 to 3.52, P=0.12). GBC patients with PBM were 10 years younger than those
      without PBM (SMD: -9.90, 95% CI: -11.70 to -8.10, P<0.00001). And a difference in
      the incidence of associated gallstone was found between GBC patients with and
      without PBM (10.8% vs 54.3%, OR: 0.09, 95% CI: 0.05 to 0.17, P<0.00001). Among
      the GBC patients with PBM, associated congenital dilatation of the common bile
      duct was present with a higher incidence ranging from 52.2% to 85.7%, and 70.0%
      85.7% of them belonged to the P-C type of PBM (the main pancreatic duct enters
      the common bile duct). No substantial heterogeneity was found and no evidence of
      publication bias was observed. CONCLUSIONS: PBM is a high-risk factor for
      developing GBC, especially the P-C type of PBM without congenital dilatation of
      the common bile duct. To prevent GBC, laparoscopic cholecystectomy is highly
      recommended for PBM patients without congenital dilatation of the common bile
      duct, especially relatively young female patients without gallstones.

PMID- 22146620
TI  - Reconstruction of the middle hepatic vein tributary in adult right lobe living
      donor liver transplantation.
AB  - BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use
      of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic
      congestion and disturbance of venous drainage. To solve this problem, we
      successfully used cadaveric venous allografts preserved in 4  degrees C
      University of Wisconsin (UW) solution within 10 days as interposition veins for
      drainage of the paramedian portion of the right lobe in adult LDLT. METHODS: From
      June 2007 to January 2008, 11 adult LDLT patients received modified right liver
      grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were
      preserved and reconstructed using cadaveric interposition vein allografts that
      had been stored for 1 to 10 days in 4  degrees C UW solution. The regeneration of
      the paramedian sector of the grafts and the patency of the interposition vein
      allografts were examined by Doppler ultrasonography after the operation. RESULTS:
      MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of
      renal failure and severe pulmonary infection on day 9 after transplantation
      without any hemiliver venous outflow obstruction. The other 8 recipients achieved
      long-term survival with a median follow-up of 30 months. The cumulative patency
      rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and
      36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the
      paramedian sectors was equivalent. CONCLUSION: The cadaveric venous allograft
      preserved in 4  degrees C UW solution within 10 days serves as a useful
      alternative for interposition veins in facilitating implantation of a right lobe
      graft and guarantees outflow of the MHV.

PMID- 22146621
TI  - Early lactate clearance as a reliable predictor of initial poor graft function
      after orthotopic liver transplantation.
AB  - BACKGROUND: Initial poor graft function (IPGF) following orthotopic liver
      transplantation is a major determinant of postoperative survival and morbidity.
      Lactate clearance is a good marker of liver function. In this study, we
      investigated the clinical utility of early lactate clearance as an early and
      accurate predictor for IPGF following liver transplantation. METHODS: This was a
      prospective observational study of 222 patients referred to the surgical
      intensive care unit (SICU) after orthotopic liver transplantation. The IPGF group
      consisted of patients with alanine aminotransferase (ALT) and/or aspartate
      aminotransferase (AST) >1500 IU/L within 72 hours after orthotopic liver
      transplantation. Early lactate clearance was defined as lactate at SICU
      presentation (hour 0) minus lactate at hour 6, divided by lactate at SICU
      presentation. The model for end-stage liver disease (MELD) score, Child-Pugh
      score and laboratory data including AST, ALT, total bilirubin (TB) and
      prothrombin time (PT) were recorded at SICU presentation and compared between the
      non-IPGF and IPGF groups. Receiver operating characteristic (ROC) curves were
      plotted to measure the performance of early lactate clearance, MELD score, Child
      Pugh score, TB and PT. RESULTS: IPGF occurred in 45 of the 222 patients (20.3%).
      The early lactate clearance in the non-IPGF group was markedly higher than that
      in the IPGF group (43.2+/-13.8% vs 13.4+/-13.7% P<0.001). The optimum cut-off
      value for early lactate clearance predicting IPGF was 24.8% (sensitivity 95.5%,
      specificity 88.9%). The area under the curve of the ROC was 0.961, which was
      significantly superior to MELD score, Child-Pugh score, TB and PT. Patients with
      early lactate clearance <=24.8% had a higher IPGF rate (OR=169) and a higher risk
      of in-hospital mortality (OR=3.625). CONCLUSIONS: Early lactate clearance can
      serve as a prompt and accurate bedside predictor of IPGF. Patients with early
      lactate clearance less than 24.8% are associated with a higher incidence of IPGF.

PMID- 22146622
TI  - Polymorphisms of CCL3L1/CCR5 genes and recurrence of hepatitis B in liver
      transplant recipients.
AB  - BACKGROUND: The genetic diversity of chemokines and chemokine receptors has been
      associated with the outcome of hepatitis B virus infection. The aim of this study
      was to evaluate whether the copy number variation in the CCL3L1 gene and the
      polymorphisms of CCR5Delta32 and CCR5-2459A->G (rs1799987) are associated with
      recurrent hepatitis B in liver transplantation for hepatitis B virus infection
      related end-stage liver disease. METHODS: A total of 185 transplant recipients
      were enrolled in this study. The genomic DNA was extracted from whole blood, the
      copy number of the CCL3L1 gene was determined by a quantitative real-time PCR
      based assay, CCR5Delta32 was detected by a sizing PCR method, and a single
      nucleotide polymorphism in CCR5-2459 was detected by restriction fragment length
      polymorphism PCR. RESULTS: No CCR5Delta32 mutation was detected in any of the
      individuals from China. Neither copy number variation nor polymorphism in CCR5
      2459 was associated with post-transplant re-infection with hepatitis B virus.
      However, patients with fewer copies (<4) of the CCL3L1 gene compared with the
      population median in combination with the CCR5G allele had a significantly higher
      risk for recurrent hepatitis B (odds ratio=1.93, 95% CI: 1.00-3.69; P=0.047).
      CONCLUSION: Patients possessing the compound decreased functional genotype of
      both CCL3L1 and CCR5 genes might be more likely to have recurrence of hepatitis B
      after transplantation.

PMID- 22146623
TI  - Harmine induces apoptosis in HepG2 cells via mitochondrial signaling pathway.
AB  - BACKGROUND: Harmine has antitumor and antinociceptive effects, and inhibits human
      DNA topoisomerase. However, no detailed data are available on the mechanisms of
      action of harmine in hepatocellular carcinoma. This study aimed to investigate
      the effects of harmine on proliferation and apoptosis, and the underlying
      mechanisms in the human hepatocellular carcinoma cell line HepG2. METHODS: The
      proliferation of HepG2 cells was determined by the cell counting kit-8 (CCK-8)
      assay and the clone formation test. The morphology of HepG2 cells was examined
      using fluorescence microscopy after Hoechst 33258 staining. Annexin V/propidium
      iodide (PI) was used to analyze apoptosis and PI to analyze the cell cycle.
      Western blotting was used to assess expression of the apoptosis-regulated genes
      Bcl-2, Bax, Bcl-xl, Mcl-1, caspase-3, and caspase-9. Mitochondrial transmembrane
      potential (psim) was determined using JC-1. RESULTS: Harmine inhibited the
      proliferation of HepG2 cells in a dose-dependent manner. Hoechst 33258 staining
      revealed nuclear fragmentation and chromosomal condensation, cell shrinkage, and
      attachment loss in HepG2 cells treated with harmine. The percentage of the sub/G1
      fraction was increased in a concentration-dependent manner, indicating apoptotic
      cell death. PI staining showed that harmine changed the cell cycle distribution,
      by decreasing the proportion of cells in G0/G1 and increasing the proportion in S
      and G2/M. Harmine induced apoptosis in a concentration-dependent manner, with
      rates of 20.0%, 32.7% and 64.9%, respectively. JC-1 revealed a decrease in psim.
      Apoptosis of HepG2 cells was associated with caspase-3 and caspase-9 activation,
      down-regulation of Bcl-2, Mcl-1, and Bcl-xl, and no change in Bax. CONCLUSIONS:
      Harmine had an anti-proliferative effect in HepG2 cells by inducing apoptosis.
      Mitochondrial signal pathways were involved in the apoptosis. The cancer-specific
      selectivity shown in this study suggested that harmine is a promising novel drug
      for human hepatocellular carcinoma.

PMID- 22146624
TI  - YKL-40 expression in human hepatocellular carcinoma: a potential biomarker?
AB  - BACKGROUND: YKL-40 is a new biomarker with diagnostic value in many different
      cancers. Whether it may serve as a biomarker for hepatocellular carcinoma (HCC)
      is still unclear. This study aimed to examine the expression of YKL-40 in the
      serum and liver tissues of HCC patients and in HCC cell lines, in comparison with
      that in non-HCC liver disease patients and non-tumor hepatic cell lines,
      respectively. METHODS: Immunohistochemical staining was used to detect YKL-40
      protein expression in liver biopsy specimens from 8 HCC patients. ELISA was used
      to assess the serum YKL-40 level in 90 HCC patients, 90 inactive HBsAg carrier
      (IHC) patients with normal liver functions, and 90 liver cirrhosis patients. Real
      time PCR was used to determine the YKL-40 mRNA expression in three HCC cell lines
      and two non-tumor hepatic cell lines. RESULTS: Immunohistochemical staining of
      liver biopsy specimens from HCC patients showed that the YKL-40 protein
      expression in tumor tissue was higher than that in adjacent normal tissues. ELISA
      revealed that the YKL-40 serum level in the HCC group was significantly higher
      than that in the IHC group, but not significantly different from that in the
      cirrhosis group. Real-time PCR showed that YKL-40 mRNA levels in HCC cell lines
      were significantly higher than those in non-tumor hepatic cells. CONCLUSIONS: YKL
      40 is highly expressed in HCC at the molecular, cellular and tissue levels.
      However, it may not serve as a serum biomarker for HCC because measurement of the
      serum YKL-40 level cannot distinguish HCC from cirrhosis.

PMID- 22146625
TI  - Fulminant liver failure models with subsequent encephalopathy in the mouse.
AB  - BACKGROUND: A reliable model of fulminant liver failure (FLF) is urgently
      required in this research field. This study aimed to develop a murine FLF model.
      METHODS: We used three groups of male C57BL/6 mice: control, with azoxymethane
      treatment (AOM group), and with galactosamine and tumor necrosis factor-alpha
      treatment (Gal+TNF-alpha group). The effects of body temperature (BT) control on
      survival in all three groups were investigated. Using BT control, we compared the
      survival, histopathological findings and biochemical/coagulation profiles between
      the two experimental groups. The effects of hydration on international normalized
      ratios of prothrombin time (PT-INRs) were also checked. Dose-dependent survival
      curves were constructed for both experimental groups. Neurological behavior was
      assessed using a coma scale. RESULTS: No unexpected BT effects were seen in the
      control group. The AOM group, but not the Gal+TNF-alpha group, showed a
      significant difference in survival curves between those with and without BT care.
      Histopathological assessment showed consistent FLF findings in both experimental
      groups with BT care. There were significant differences between the experimental
      groups in aspartate aminotransferase levels and PT-INRs, and significant
      differences in PT-INRs between the sufficiently and insufficiently hydrated
      groups. There were significant differences between FLF models in the duration of
      each coma stage, with significant differences in stages 1 and 3 as percentages of
      the disease state (stages 1-4). The two FLF models with BT care showed different
      survival curves in the dose-dependent survival study. CONCLUSIONS: AOM provides a
      good FLF model, but requires a specialized environment and careful BT control.
      Other FLF models may also be useful, depending on the research purpose.
      Thoughtful attention to caregiving and close observation are indispensable for
      successful FLF models.

PMID- 22146626
TI  - Clinicopathological analysis of 14 patients with combined hepatocellular
      carcinoma and cholangiocarcinoma.
AB  - BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is
      an uncommon subtype of primary hepatic carcinoma, and its prognosis is poor. This
      study was undertaken to investigate the prognosis and the clinicopathological
      characteristics of cHCC-CC, including their possible cellular origin. METHODS:
      Among 852 patients with a primary hepatic carcinoma who underwent hepatectomy
      from January 1998 to April 2008 at our hospital, cHCC-CC was identified in 14
      patients. The clinicopathological characteristics of the 14 patients were
      analyzed retrospectively. The expression of the liver stem cell markers (c-kit,
      CD90, CD133 and CK19) in the tumor tissue was detected by immunohistochemistry,
      and the Kaplan-Meier method was used to evaluate survival. RESULTS: Among the 14
      patients, 9 presented with abdominal pain, 3 with anorexia and debilitation, and
      the remaining two patients were asymptomatic. The mean age was 53.6+/-3.0 (range
      38-74) years. Among the included patients, 11 had an elevated serum alpha
      fetoprotein level, 13 were infected with hepatitis B virus, 9 had vascular
      invasion and 1 had lymph node metastasis. The average diameter of the tumors was
      9.9+/-1.1 (range 5.0-16.0) cm. The median overall survival time was 7.9+/-1.0
      months. In addition, the presence of the liver stem cell markers, c-kit, CD90,
      CD133 and CK19 was 71.4%, 85.7%, 92.9% and 78.6%, respectively. All four markers
      were simultaneously expressed in eight cases. CONCLUSIONS: cHCC-CC has aggressive
      characteristics and the prognosis is extremely dismal. The high expression of
      liver stem cell markers in the tumor tissue suggests that these tumors may derive
      from liver stem cells.

PMID- 22146627
TI  - Risk factors of intrahepatic cholangiocarcinoma in patients with hepatolithiasis:
      a case-control study.
AB  - BACKGROUND: Why 3.3% to 10% of all patients with hepatolithiasis develop
      intrahepatic cholangiocarcinoma (ICC) remains unknown. We carried out a hospital
      based case-control study to identify risk factors for the development of ICC in
      patients with hepatolithiasis in China. METHODS: Eighty-seven patients with
      pathologically diagnosed hepatolithiasis associated with ICC and 228 with
      hepatolithiasis alone matched by sex, age (+/-2 years), hospital admittance and
      place of residence were interviewed during the period of 2000-2008. Odds ratios
      (OR) and 95% confidence intervals (CI) were calculated for each risk factor.
      RESULTS: Among the patients with hepatolithiasis associated with ICC, the mean
      age was 57.7 years and 61.0% were female. Univariate analysis showed that the
      significant risk factors for ICC development in hepatolithiasis were smoking,
      family history of cancer, appendectomy during childhood (under age 20), and
      duration of symptoms >10 years. In multivariate stepwise logistic regression
      analysis, smoking (OR=1.931, 95% CI: 1.000-3.731), family history of cancer
      (OR=5.175, 95% CI: 1.216-22.022), and duration of symptoms >10 years (OR=2.348,
      95% CI: 1.394-3.952) were independent factors. CONCLUSION: Smoking, family
      history of cancer and duration of symptoms >10 years may be risk factors for ICC
      in patients with hepatolithiasis.

PMID- 22146629
TI  - Technical tailoring of pancreaticoduodenectomy in patients with hepatic artery
      anatomic variants.
AB  - BACKGROUND: Pancreaticoduodenectomy is the treatment of choice for periampullary
      and pancreatic head tumors. In case of hepatic artery abnormalities, early
      pancreatic transection during pancreaticoduodenectomy may prove inappropriate.
      Early retroportal lamina dissection improves exposure of the superior mesenteric
      vessels and anatomic variants of the hepatic artery, where safeguarding is
      mandatory. METHOD: We describe our early retroportal lamina approach in patients
      with anatomic variants of the hepatic artery before pancreatic transection.
      RESULTS: This approach was used during 42 pancreaticoduodenectomies with a
      hepatic artery anatomic variant which was spared in 40 patients. Arterial
      reconstruction was performed in 2 patients. Five patients with a hepatic artery
      variant and adenocarcinoma involving the portomesenteric junction required venous
      resection and reconstruction. CONCLUSIONS: Early retroportal lamina dissection
      during pancreaticoduodenectomy in patients with hepatic artery anatomic variants
      enables easier exposure, avoiding injuries that might compromise the liver
      arterial supply. When the portomesenteric vein is involved, this approach
      facilitates en bloc "no touch" venous resection and reconstruction.

PMID- 22146628
TI  - Protective effects of Ligustrazine, Kakonein and Panax Notoginsenoside on the
      small intestine and immune organs of rats with severe acute pancreatitis.
AB  - BACKGROUND: Severe acute pancreatitis (SAP) is characterized by fatal pathogenic
      conditions and a high mortality. It is important to study SAP complicated with
      multiple organ injury. In this study we compared the protective effects of three
      traditional Chinese medicines (Ligustrazine, Kakonein and Panax Notoginsenoside)
      on the small intestine and immune organs (thymus, spleen and lymph nodes) of rats
      with SAP and explored their mechanism of action. METHODS: One hundred forty-four
      rats with SAP were randomly divided into model control, Ligustrazine-treated,
      Kakonein-treated, and Panax Notoginsenoside-treated groups (n=36 per group).
      Another 36 normal rats comprised the sham-operated group. According to the
      different time points after operation, the experimental rats in each group were
      subdivided into 3-, 6- and 12-hour subgroups (n=12). At various time points after
      operation, the mortality rate of rats and pathological changes in the small
      intestine and immune organs were recorded and the serum amylase levels were
      measured. RESULTS: Compared to the model control groups, the mortality rates in
      all treated groups declined and the pathological changes in the small intestine
      and immune tissues were relieved to different degrees. The serum amylase levels
      in the three treated groups were significantly lower than those in the model
      control group at 12 hours. The pathological severity scores for the small
      intestinal mucosa, thymus and spleen (at 3 and 12 hours) in the Ligustrazine
      treated group, for the thymus (at 3 and 12 hours) and spleen (at 3 and 6 hours)
      in the Kakonein-treated group, and for the thymus (at 3 hours) and spleen (at 3
      hours) in the Panax Notoginsenoside-treated group were significantly lower than
      those in the model control group. The pathological severity scores of the small
      intestinal mucosa (at 6 and 12 hours) and thymus (at 6 hours) in the Ligustrazine
      treated group were significantly lower than those in the Kakonein- and Panax
      Notoginsenoside-treated groups. CONCLUSIONS: All the three traditional Chinese
      drugs significantly alleviated the pathological changes in the small intestine
      and immune organs of SAP rats. Ligustrazine was the most effective one among
      them.

PMID- 22146630
TI  - Hemoperitoneum in cirrhotic patients without abdominal trauma or tumor.
AB  - BACKGROUND: Hemoperitoneum is associated with several emergency conditions and is
      especially evident when it occurs in patients with liver cirrhosis. This study
      aimed to assess the clinical characteristics of cirrhotic patients who did not
      have abdominal trauma or tumor but who developed hemoperitoneum. METHODS: We
      reviewed the clinical records of 1276 consecutive cirrhotic patients with
      hemoperitoneum at our center between January 2007 and December 2009.
      Hemoperitoneum was confirmed by abdominal paracentesis. RESULTS: Of the 1276
      cirrhotic patients, 19 were found to have hemoperitoneum, but only 6 did not have
      abdominal trauma or tumor. The occurrence of spontaneous hemoperitoneum in the
      cirrhotic patients was therefore 0.5%. Hemoperitoneum can occur spontaneously in
      severely decompensated cirrhotic patients with intra-abdominal collateral vessels
      and high scores on the model for end-stage liver disease and Child-Pugh-Turcotte
      test. Most patients presented with abdominal distension, abdominal pain,
      increased abdominal girth and hemodynamic instability with a significant drop in
      the hemoglobin level. Three patients died of hemorrhagic shock within 24 hours,
      and the other 3 died of hepatic encephalopathy or spontaneous bacterial
      peritonitis after 5 to 10 days because of further decompensation of the liver.
      CONCLUSIONS: Hemoperitoneum can occur in cirrhotic patients who do not have
      abdominal trauma or tumor. It mainly occurs in severely decompensated end-stage
      cirrhotic patients. Cirrhotic patients with hemoperitoneum have a poor prognosis.

PMID- 22146631
TI  - Modulation of graft vascular inflow guided by flowmetry and manometry in liver
      transplantation.
AB  - BACKGROUND: Survival of the partial graft after living donor liver
      transplantation owes much to its tremendous regenerative ability. With excellent
      venous outflow capacity, a graft within a wide range of graft-to-standard-liver
      volume ratios can cope with portal hypertension that is common in liver
      transplant recipients. However, when the ratio range is exceeded, modulation of
      graft vascular inflow becomes necessary for graft survival. The interplay between
      graft-to-standard-liver-volume ratio and portal pressure, in the presence of
      portosystemic shunt or otherwise, requires individualized modulation of graft
      portal and arterial inflows. Boosting of portal inflow by shunt ligation can be
      guided by transonic flowmetry, whereas muting of portal inflow by splenic artery
      ligation can be monitored by portal electronic manometry. METHOD: We describe
      four cases to illustrate the above. RESULTS: One patient had hepatic artery
      thrombosis resulting from splenic artery steal syndrome which was the sequela of
      small-for-size syndrome. Emergency splenic artery ligation and re-anastomosis of
      the hepatic artery successfully muted the portal inflow and boosted the hepatic
      arterial inflow. Another patient with portal vein thrombosis underwent
      thrombendvenectomy. Portal inflow was boosted with ligation of portosystemic
      shunt, which is often present in these patients with portal hypertension. The
      coexistence of splenic aneurysm and splenorenal shunt required ligation of both
      in the third patient. The fourth patient, with portal pressure and flow
      monitoring, avoided ligation of a coronary vein which became a main portal inflow
      after portal thrombendvenectomy. CONCLUSION: Management of graft inflow
      modulation guided selectively by transonic flowmetry or portal manometry was
      described.

PMID- 22146632
TI  - Undifferentiated embryonal sarcoma of the liver presenting as a hemorrhagic
      cystic tumor in an adult.
AB  - BACKGROUND: Undifferentiated embryonal sarcoma (UES) of the liver is a rare,
      highly malignant neoplasm with a poor prognosis occurring almost exclusively in
      late childhood (6-10 years of age). Only a few cases have been reported in
      adults, accounting for less than 1% of all primary liver neoplasms. METHODS: A 47
      year-old woman presented with a palpable mass in the left upper abdomen. Magnetic
      resonance imaging revealed a 12x10 cm cystic mass with hemorrhage in the left
      lateral segment of the liver. The initial impression was a hemorrhagic cystic
      tumor of the liver. The patient underwent a left lateral sectionectomy of the
      liver. Histopathology and immunohistochemistry helped make a diagnosis of UES.
      RESULTS: The patient recovered uneventfully and received systemic chemotherapy.
      Radiologic examination for follow-up revealed a metastatic lesion in the lumbar
      spine (L5). She was subjected to radiotherapy at the lumbar spine. She survived
      48 months. CONCLUSION: Although hepatic cyst as UES of the liver is difficult to
      diagnose because of its rarity in adults and lack of specific findings, it should
      be considered in a differential diagnosis.

PMID- 22146633
TI  - Making mistakes in 2012--let's do it!
AB  - As the new health care laws and regulations are defined and quickly changing, we
      must be nimble, allow our colleagues to attempt new ways of solving old problems,
      make mistakes if necessary, observe, take note, and discover the new best
      practices.

PMID- 22146634
TI  - Canada's National Case Management Network developing a national case management:
      competency framework.

PMID- 22146635
TI  - The 6 dimensions of promising practice for case managed supports to end
      homelessness: part 2:  the 6 dimensions of quality.
AB  - PURPOSE/OBJECTIVES: Homelessness is a social condition increasing in frequency
      and severity across Canada. Interventions to end and prevent homelessness include
      effective case management in addition to an affordable housing provision. Little
      standardization exists for service providers to guide their decision making in
      developing and maintaining effective case management programs. The purpose of
      this 2-part article is to articulate dimensions of promising practice for case
      managers working in a "Housing First" context. Part 1 discusses research
      processes and findings and Part 2 articulates the 6 dimensions of quality.
      PRIMARY PRACTICE SETTING: Practice settings include community-based organizations
      that employ and support case managers whose primary role is moving people from
      homelessness into permanent supportive housing. FINDINGS/CONCLUSIONS: Six
      dimensions of promising practice are critically important to reducing barriers,
      improving sector collaboration, and ensuring that case managers have appropriate
      and effective training and support. Dimensions of promising practice are (1)
      collaboration and cooperation-a true team approach; (2) right matching of
      services-person-centered; (3) contextual case management-culture and flexibility;
      (4) the right kind of engagement-relationships and advocacy; (5) coordinated and
      well-managed system-ethics and communication; and (6) evaluation for success
      support and training. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Effective,
      coordinated case management, in addition to permanent affordable housing has the
      potential to reduce a person's or family's homelessness permanently.
      Organizations and professionals working in this context have the opportunity to
      improve processes, reduce burnout, collaborate and standardize, and, most
      importantly, efficiently and permanently end someone's homelessness with the help
      of dimensions of quality for case management.

PMID- 22146637
TI  - Affordable Care Act: predictive modeling challenges and opportunities for case
      management.
AB  - PURPOSE/OBJECTIVES: The move to the Accountable Care Organization model of care
      calls for broad-sweeping structural, operational, and cultural changes in our
      health care systems. The use of predictive modeling as part of the discharge
      process is used as a way to highlight just one of the common processes that will
      need to be transformed to maximize reimbursement under the Accountable Care
      Organization model. The purpose of this article is to summarize what has been
      learned about predictive modeling from the population health management industry
      perspective, to discuss how that knowledge might be applied to discharge planning
      in the Accountable Care Organization model of patient care, and then to outline
      how the Accountable Care Organization environment presents various challenges,
      opportunities, and implications for the case management role. PRIMARY PRACTICE
      SETTING(S): Hospitals, physician practices. FINDINGS/CONCLUSIONS: The development
      of predictive models to identify patients at risk for readmission is described
      and how such models can positively impact the discharge planning process by
      lowering readmission rates. Examples of the structural, operational, cultural,
      and case management role changes necessary to maximize the benefits of an
      Accountable Care Organization are described. IMPLICATIONS FOR CASE MANAGEMENT
      PRACTICE: There is a growing need for advanced practice nurses to fill the
      leadership, resource management, analytical, informatics-based, and
      organizational development roles that are sorely needed to advance the
      Accountable Care Organization model of care. Case managers are well-positioned to
      lend their expertise to the development efforts, but they will need to be
      educationally prepared for the many advanced practice roles that will emerge as
      our nation evolves this new system of health care delivery.

PMID- 22146639
TI  - An analysis of a case manager-driven emergent dialysis program.
AB  - PURPOSE OF THE STUDY: With the undocumented immigrant population in the United
      States on the rise, an increase in the number of patients with end-stage renal
      disease without access to a regular dialysis chair continues. This leaves
      hospital systems with the difficult decision of how best to care for this
      population. We sought to evaluate the feasibility, effectiveness, and costs of a
      case manager-driven emergent dialysis program. We hypothesized that this program
      would be feasible and would result in similar costs as the previous regularly
      scheduled dialysis program in place at our institution. PRIMARY PRACTICE SETTING:
      The study was conducted at Wishard Memorial Hospital, which is an urban public
      hospital in Indianapolis, IN. METHODOLOGY AND SAMPLE: We performed a before
      (March 11, 2010, to June 11, 2010) and after (June 14, 2010, to September 14,
      2010) study to compare the treatment of a 6-patient cohort of dialysis patients
      without a "dialysis home" before and after the case manager-driven emergent
      dialysis program, using secondary data. RESULTS: The case manager-driven emergent
      dialysis process was feasible and led to a total expense of $101,802 as compared
      with a total cost of $122,890 when providing regular dialysis to this subset of
      patients. There were no differences in intensive care unit days, length of stay,
      and complications between the 2 groups in the short study period. IMPLICATIONS
      FOR CASE MANAGEMENT PRACTICE: The dialysis population without a "dialysis home"
      is a high-risk population in need of intensive medical care but the approach to
      these patients continues to be debated. Although this study does not prove or
      necessarily support a dialysis on "emergent" basis approach over chronic,
      scheduled dialysis, the study does demonstrate that case management can play a
      significant role in the care of these patients. Case management oversight and
      management of our patient population resulted in costs equal to, or better than,
      those who received chronic dialysis care without a difference in complications
      over a 6-month study period.

PMID- 22146640
TI  - Enhancing the team approach to care with professional case management.

PMID- 22146641
TI  - Heroes:  case managers and caregivers.

PMID- 22146642
TI  - The ever-changing legal landscape.

PMID- 22146643
TI  - Why we do what we do:  case managers unite multidisciplinary team around injured
      patient.

PMID- 22146644
TI  - What every case manager needs to know about the ADAAA!

PMID- 22146646
TI  - Saudi Arabia has several strategies to care for pilgrims on the Hajj.

PMID- 22146645
TI  - Ongoing Notch signaling maintains phenotypic fidelity in the adult exocrine
      pancreas.
AB  - The Notch signaling pathway regulates embryonic development of the pancreas,
      inhibiting progenitor differentiation into exocrine acinar and endocrine islet
      cells. The adult pancreas appears to lack progenitor cells, and its mature cell
      types are maintained by the proliferation of pre-existing differentiated cells.
      Nonetheless, Notch remains active in adult duct and terminal duct/centroacinar
      cells (CACs), in which its function is unknown. We previously developed mice in
      which cells expressing the Notch target gene Hes1 can be labeled and manipulated,
      by expression of Cre recombinase, and demonstrated that Hes1(+) CACs do not
      behave as acinar or islet progenitors in the uninjured pancreas, or as islet
      progenitors after pancreatic duct ligation. In the current study, we assessed the
      function of Notch signaling in the adult pancreas by deleting the transcription
      factor partner of Notch, Rbpj, specifically in Hes1(+) cells. We find that loss
      of Rbpj depletes the pancreas of Hes1-expressing CACs, abrogating their ongoing
      contribution to growth and homeostasis of more proximal duct structures. Upon
      Rbpj deletion, CACs undergo a rapid transformation into acinar cells, suggesting
      that constitutive Notch activity suppresses the acinar differentiation potential
      of CACs. Together, our data provide direct evidence of an endogenous genetic
      program to control interconversion of cell fates in the adult pancreas.

PMID- 22146647
TI  - Ghosts in the machine.

PMID- 22146648
TI  - Time to reconsider NICE guidance on heparin prophylaxis in medical inpatients.

PMID- 22146649
TI  - BMJ is in danger of losing sight of the patient.

PMID- 22146650
TI  - Money is the greatest conflict of all.

PMID- 22146651
TI  - MMR is but the tip of the iceberg.

PMID- 22146653
TI  - Questions about selection, exposure, and tumour incidence.

PMID- 22146654
TI  - Updated study contains poor science and should be disregarded.

PMID- 22146656
TI  - Cameron promotes new partnership between research, industry, and the NHS.

PMID- 22146657
TI  - Brokering a deal to replace Kyoto will take years, EU ministers say.

PMID- 22146658
TI  - Government has not acted to avoid repeat of Southern Cross care home collapse,
      say MPs.

PMID- 22146659
TI  - Local and non-local native topologies reveal the underlying folding landscape of
      proteins.
AB  - Due to Plaxco, Simons, Baker and others, it is now well known that the two-state
      single domain protein folding rate is fairly well predicted from knowledge of the
      topology of the native structure. Plaxco et al found that the folding rates of
      two-state proteins correlate with the average degree to which native contacts are
      'local' within the chain sequence: fast-folders usually have mostly local
      structures. Here, we dissected the native topology further by focusing on non
      local and local contacts using lower and upper bounds of allowable sequence
      separation in computing the average contact order. We analyzed non-local and
      local contacts of 82 two-state proteins whose experimental folding rates span
      over six orders of magnitude. We observed that both the number of non-local
      contacts and the average sequence separation of non-local contacts (non-local CO)
      are both negatively correlated with the folding rate, showing that the non-local
      contacts dominate the barrier-crossing process. Surprisingly, the local contact
      orders of the proteins also correlate with the folding rates. However, this
      correlation shows a strong positive trend indicating the role of a diffusive
      search in the denatured basin.

PMID- 22146660
TI  - NDLSTM instructors practice what they teach.

PMID- 22146661
TI  - CDC's 2009 H1N1 vaccine pharmacy initiative in the United States: implications
      for future public health and pharmacy collaborations for emergency response.

PMID- 22146662
TI  - E-health in preparedness and response.

PMID- 22146663
TI  - The importance of journals to the growing discipline of disaster medicine.

PMID- 22146664
TI  - Commercial products that convey personal health information in emergencies.
AB  - OBJECTIVE: Describe commercially available products and services designed to
      convey personal health information in emergencies. METHODS: The search engine
      Google(r), supplemented by print ads, was used to identify companies and
      organizations that offer relevant products and services to the general market.
      Disease-specific, health system, and health plan-specific offerings were
      excluded. Vendor web sites were the primary sources of information, supplemented
      by telephone and e-mail queries to sales representatives. Perfect inter-rater
      agreement was achieved. RESULTS: Thirty-nine unique vendors were identified.
      Eight sell engraved jewelry. Three offer an embossed card or pamphlet. Twelve
      supply USB drives with various features. Eleven support password-protected web
      sites. Five maintain national call centers. Available media differed markedly
      with respect to capacity and accessibility. Quoted prices ranged from a one-time
      expenditure of $3.50 to an annual fee of $200. Associated features and annual
      fees varied widely. CONCLUSION: A wide range of products and services exist to
      help patients convey personal health information. Health care providers should be
      familiar with their features, so they can access the information in a disaster or
      emergency.

PMID- 22146665
TI  - A home toolkit for primary prevention of influenza by individuals and families.
AB  - An influenza pandemic can overwhelm the capacities of hospitals, clinics, nursing
      facilities, and emergency services. The likelihood is that most of the
      individuals who are stricken will be cared for at home, and there is strong
      evidence that in-home caregivers bear a disproportionate risk of becoming
      infected. We reviewed the scientific literature after 2000 to identify steps that
      in-home caregivers can take to reduce the chances that they and other household
      members will become infected in the home. Personal hygiene, common masks, and
      technologies including air filters and UV light each offer incremental benefits,
      and in combination are expected to reduce a portion of the risk that household
      members face when caring for a member who has become infected. In pandemics and
      even seasonal epidemics, seemingly small steps can literally mean the difference
      between life and death, especially for in-home caregivers.

PMID- 22146666
TI  - Deepwater horizon oil spill: mental health effects on residents in heavily
      affected areas.
AB  - BACKGROUND: Mental health issues are a significant concern after disasters such
      as the Deepwater Horizon oil spill in the Gulf of Mexico in 2010. This study was
      designed to assess the mental health effects on residents of areas of
      southeastern Louisiana affected by the oil spill. METHODS: Telephone and face-to
      face interviews were conducted with residents (N = 452) assessing concerns and
      direct impact. RESULTS: The results show that the greatest effect on mental
      health related to the extent of disruption to participants' lives, work, family,
      and social engagement, with increased symptoms of anxiety, depression, and
      posttraumatic stress. Given the location of the oil spill affecting communities
      that had been devastated by Hurricane Katrina, results also revealed that losses
      from Hurricane Katrina were highly associated with negative mental health
      outcomes. Conversely, the ability to rebound after adversity and place
      satisfaction were highly associated with better mental health outcomes.
      CONCLUSIONS: Enhanced understanding of mental health effects after the Deepwater
      Horizon oil spill will help in determining directions for much-needed mental
      health services after the disaster and in contributing to the knowledge of
      complex traumatization and the ability to rebound after adversity.

PMID- 22146667
TI  - Results of rapid needs assessments in rural and urban Iowa following large-scale
      flooding events in 2008.
AB  - BACKGROUND: On June 8 and 9, 2008, more than 4 inches of rain fell in the Iowa
      Cedars River Basin causing widespread flooding along the Cedar River in Benton,
      Linn, Johnson, and Cedar Counties. As a result of the flooding, there were 18
      deaths, 106 injuries, and over 38,000 people displaced from their homes; this
      made it necessary for the Iowa Department of Health to conduct a rapid needs
      assessment to quantify the scope and effect of the floods on human health.
      METHODS: In response, the Iowa Department of Public Health mobilized interview
      teams to conduct rapid needs assessments using Geographic Information Systems
      (GIS)-based cluster sampling techniques. The information gathered was
      subsequently employed to estimate the public health impact and significant human
      needs that resulted from the flooding. RESULTS: While these assessments did not
      reveal significant levels of acute injuries resulting from the flood, they did
      show that many households had been temporarily displaced and that future health
      risks may emerge as the result of inadequate access to prescription medications
      or the presence of environmental health hazards. CONCLUSIONS: This exercise
      highlights the need for improved risk communication measures and ongoing
      surveillance and relief measures. It also demonstrates the utility of rapid needs
      assessment survey tools and suggests that increasing use of such surveys can have
      significant public health benefits.

PMID- 22146668
TI  - Symptoms of anxiety, depression, and posttraumatic stress among survivors of the
      2005 Pakistani earthquake.
AB  - OBJECTIVES: To assess and compare the prevalence of psychological morbidity among
      survivors of the 2005 northern Pakistan earthquake from Azad Kashmir and the
      Northwest Frontier Province (NWFP). METHODS: We conducted a cross-sectional study
      among randomly sampled survivors (N = 361) of the earthquake living in camps at
      the time of the interview, approximately 6 months after the earthquake. RESULTS:
      The prevalence of posttraumatic stress disorder (PTSD) symptoms in the total
      sample was 51.5% and the prevalence of individuals who received positive scores
      on the Hopkins Symptom Checklist (HSCL) was 75%. The prevalence rates for anxiety
      and depression symptoms were 77.3% and 70.9%, respectively. The prevalence in
      Azad Kashmir was 57.9% for PTSD and 79.8% for positive HSCL, and NWFP had 41.3%
      PTSD and 67.4% positive HSCL. Study subjects from Azad Kashmir were approximately
      2 times as likely to have PTSD or a positive HSCL when compared to subjects from
      NWFP (odds ratio 1.95, confidence interval 1.27-3.0; P = .0024) and (odds ratio
      1.91, confidence interval 1.18-3.1; P = .0085), respectively. CONCLUSIONS: Nearly
      half of the northern Pakistan earthquake survivors had symptoms of PTSD. Six
      months after the incident, more than three-fourths exhibited symptoms of an
      anxiety disorder.

PMID- 22146669
TI  - Health care workers' ability and willingness to report to work during public
      health emergencies.
AB  - OBJECTIVES: We conducted a county-wide survey to assess the ability and
      willingness of health care workers to report to work during a pandemic influenza
      and a severe earthquake and to identify barriers and strategies that would help
      them report to work. METHODS: A stratified random sample of 9211 health care
      workers was selected from the Washington state licensure database and from health
      care agencies. We assessed correlates between self-reported ability and
      willingness to report to work and demographic and employer-related variables
      under two scenarios, influenza pandemic and a severe earthquake. RESULTS: For the
      influenza pandemic scenario, 95% of respondents reported that they would be able
      and 89% reported that they would be willing to report to their usual place of
      work. Seventy-four percent of respondents reported that they would be able and
      88% would be willing to report to their usual place of work following a severe
      earthquake. The most frequently cited strategies that would help respondents
      report to work during an influenza pandemic were the availability of anti-viral
      influenza treatment and the ability to work from home. For persons with children
      at home, the strategy to increase ability to report to work during an earthquake
      was the availability of child care. CONCLUSIONS: The majority of the King County
      health care workforce is willing and able to respond to an influenza pandemic or
      a severe earthquake.

PMID- 22146671
TI  - Cl-BODIPYs: a BODIPY class enabling facile B-substitution.
AB  - Cl-BODIPYs, synthesized in high yields from dipyrrins under air- and moisture
      free conditions, are extremely facile to substitution at boron compared to their
      corresponding F-BODIPYs, opening up a new route to BODIPYs functionalized at
      boron.

PMID- 22146672
TI  - Effects of microgeometry on the permittivity of impregnated porous media.
AB  - We propose a new approximative relation for the low-frequency dielectric
      permittivity of liquid-filled porous materials. In this formulation, effects of
      microgeometry are included through the so-called [Formula: see text] parameter.
      Our measurements on salt-water-impregnated artificial sandstones support the new
      relation. We also show that the high permittivities at low frequencies reported
      earlier for brine-impregnated sintered glass spheres (Nost  et al 1992  Phys.
      Scr. T  44 67) may be due to effects at the solid - liquid interface in the
      'bulk' porous material. The latter results are also in agreement with our
      proposed relation.

PMID- 22146674
TI  - Open-label trial and randomized, double-blind, placebo-controlled, crossover
      trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies.
AB  - BACKGROUND: Molecular hydrogen has prominent effects on more than 30 animal
      models especially of oxidative stress-mediated diseases and inflammatory
      diseases. In addition, hydrogen effects on humans have been reported in diabetes
      mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer,
      and brain stem infarction. Hydrogen effects are ascribed to specific radical
      scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also
      to signal-modulating activities, but the detailed molecular mechanisms still
      remain elusive. Hydrogen is a safe molecule that is largely produced by
      intestinal bacteria in rodents and humans, and no adverse effects have been
      documented. METHODS: We performed open-label trial of drinking 1.0 liter per day
      of hydrogen-enriched water for 12 weeks in five patients with progressive
      muscular dystrophy (PMD), four patients with polymyositis/dermatomyositis
      (PM/DM), and five patients with mitochondrial myopathies (MM), and measured 18
      serum parameters as well as urinary 8-isoprostane every 4 weeks. We next
      conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5
      liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10
      patients with DM and 12 patients with MM, and measured 18 serum parameters every
      4 weeks. RESULTS: In the open-label trial, no objective improvement or worsening
      of clinical symptoms was observed. We, however, observed significant effects in
      lactate-to-pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum
      matrix metalloproteinase-3 (MMP3) in PM/DM, and serum triglycerides in PM/DM. In
      the double-blind trial, no objective clinical effects were observed, but a
      significant improvement was detected in lactate in MM. Lactate-to-pyruvate ratios
      in MM and MMP3 in DM also exhibited favorable responses but without statistical
      significance. No adverse effect was observed in either trial except for
      hypoglycemic episodes in an insulin-treated MELAS patient, which subsided by
      reducing the insulin dose. CONCLUSIONS: Hydrogen-enriched water improves
      mitochondrial dysfunction in MM and inflammatory processes in PM/DM. Less
      prominent effects with the double-blind trial compared to the open-label trial
      were likely due to a lower amount of administered hydrogen and a shorter
      observation period, which implies a threshold effect or a dose-response effect of
      hydrogen.

PMID- 22146673
TI  - Agentic and communal traits and health: adolescents with and without diabetes.
AB  - The authors examined whether agentic and communal traits are associated with
      relationship and health outcomes among adolescents with and without diabetes.
      They interviewed 263 teens (average age 12; 132 Type 1 diabetes; 131 healthy) on
      an annual basis for 5 years. The authors measured agency, communion, unmitigated
      agency, and unmitigated communion as well as parent and peer relationship
      quality, psychological distress, and diabetes health. In concurrent and lagged
      multilevel models, unmitigated communion and unmitigated agency were associated
      with poor relationship outcomes and greater psychological distress for those with
      and without diabetes. In lagged analyses, unmitigated communion predicted
      deterioration in diabetes health. Communion and agency were associated with
      positive relationship and health outcomes, with the former being stronger than
      the latter. These results underscore the need to focus on unmitigated agency and
      unmitigated communion when studying the implications of personality for health
      during adolescence.

PMID- 22146675
TI  - Year in review 2010: Critical Care--Neurocritical care.
AB  - In 2010 Critical Care published a large number of articles on critical care
      aspects of neurologic and neurosurgical conditions. These aspects included
      investigation of diagnostic criteria for bacterial meningitis, critical illness
      myopathy and their relationship to systemic inflammation. A number of studies
      investigated the biology of sepsis-related delirium, its biomarkers, its
      relationship to inflammation and its impact on outcome. Other teams reported on
      the use of magnetic resonance imaging, biomarkers and electroencephalogram to
      predict outcome in patients who were comatose following cardiac arrest. Our
      understanding of the pathophysiology as well as management of subarachnoid
      hemorrhage was addressed in several papers. Topics included the effect of
      hemodynamic treatment of delayed cerebral ischemia, pulmonary edema and the
      impact of subarachnoid hemorrhage on endocrine function. Finally, outcome from
      neurocritical care and patients' retrospective willingness to consent to the
      treatment they received were reported.

PMID- 22146677
TI  - New versatile staining reagents for biological transmission electron microscopy
      that substitute for uranyl acetate.
AB  - Aqueous uranyl acetate has been extensively used as a superb staining reagent for
      transmission electron microscopy of biological materials. However, recent
      regulation of nuclear fuel material severely restricts its use even for purely
      scientific purposes. Since uranyl salts are hazardous due to biological toxicity
      and remaining radioactivity, development of safe and non-radioactive substitutes
      is greatly anticipated. We examined two lanthanide salts, samarium triacetate and
      gadolinium triacetate, and found that 1-10% solution of these reagents was safe
      but still possess excellent capability for staining thin sections of plastic
      embedded materials of animal and plant origin. Although post-fixation with osmium
      tetroxide was essential for high-contrast staining, post-staining with lead
      citrate could be eliminated if a slow-scan CCD camera is available for
      observation. These lanthanide salts can also be utilized as good negative
      staining reagents to study supramolecular architecture of biological
      macromolecules. They were not as effective as a fixative of protein assembly,
      reflecting the non-hazardous nature of the reagents.

PMID- 22146676
TI  - Adolescent rat circadian activity is modulated by psychostimulants.
AB  - Circadian pattern of activity regulates many aspects of mammalian physiology and
      behavior to particular times of the day by entraining the circadian clocks to
      external environmental signals. Since circadian rhythms are sensitive to many
      pharmacological agents, it is important to understand if the repetitive use of
      psychostimulants such as amphetamine will alter the circadian rhythm behavioral
      activity pattern. The present study uses male Sprague-Dawley rats to study the
      long-term effects of amphetamine on the locomotor circadian rhythm activity
      pattern. Rats were randomly assigned to a testing cage that recorded their
      locomotor activity nonstop for eleven days using the open field assay, as
      follows: one day of baseline activity was recorded and then the experimental
      group was injected with amphetamine (0.6mg/kg) for 6days, no treatment for 3days
      (i.e., washout days) and then re-challenged with amphetamine for one more day
      while the control group was treated similarly with saline. The Cosine Curve
      Statistical Analysis (CCSA) test was used to fit a 24-hour curve to activity
      pattern. Results indicate that repetitive daily amphetamine injections cause
      behavioral sensitization and a significant change of circadian rhythm of
      locomotor activity pattern, and elicit behavioral expectation to receive the drug
      or expression of withdrawal during the washout days. The results suggest that
      either changes in circadian rhythm caused sensitization and withdrawal or
      sensitization and withdrawal caused the change in circadian rhythm activity.

PMID- 22146683
TI  - Bone metastasis targeting: a novel approach to reach bone using Zoledronate
      anchored PLGA nanoparticle as carrier system loaded with Docetaxel.
AB  - In spite of good research in drug delivery, bone targeting remains largely
      unexplored. Even some of the bone diseases are seldom cured just because of poor
      distribution of drug at the bone site. Zoledronate (ZOL) having strong affinity
      towards bone and its utility in bone metastasis management makes it perfect
      ligand for bone targeting. Recent studies revealed that ZOL in combination with
      docetaxel showed significant synergism in the management of bone metastasis. From
      the results, it is clear that ZOL-conjugated PLGA nanoparticles (NPs) showed more
      cellular uptake than pegylated PLGA NPs with change in cellular uptake route. In
      vitro studies on MCF-7 and BO2 cell line revealed that ZOL anchored PLGA-PEG NPs
      showed enhanced cell cytotoxicity, increase in cell cycle arrest and more
      apoptotic activity. PLGA-PEG-ZOL NPs found to block mevalonate pathway and
      increase accumulation of apoptotic metabolites such as ApppI. In vivo animal
      studies using technetium-99m radiolabeling showed prolong blood circulation half
      life, reduced liver uptake and significantly higher retention of ZOL tagged NPs
      at the bone site with enhanced tumor retention. Here, we can conclude that the
      targeting ability of ZOL enhanced by strong affinity to bone, enhanced
      endocytosis of ZOL anchored PLGA-PEG NPs.

PMID- 22146684
TI  - Activity-dependent coordinated mobility of hippocampal inhibitory synapses
      visualized with presynaptic and postsynaptic tagged-molecular markers.
AB  - Axonal varicosities and dendritic spines at excitatory synapses are dynamic
      structures essential for synaptic plasticity, whereas the behavior of inhibitory
      synapses during development and plasticity remains largely unknown. To
      investigate the morphology and dynamics of inhibitory synapses, we used two
      distinct pre- and postsynaptic fluorescent probes: one is a yellow fluorescent
      protein, Venus, incorporated into vesicular GABA transporter (VGAT) gene as a
      specific marker of presynaptic inhibitory neurons and the other red fluorescent
      protein (mCherry)-tagged gephyrin, a postsynaptic scaffolding protein, as a
      postsynaptic marker. Using primary culture of mouse hippocampal neurons and
      confocal laser-scanning microscopy, we established a system by which close
      contacts of Venus-positive axonal varicosities with mCherry-labeled gephyrin
      clusters in the dendritic shafts of dissociated hippocampal pyramidal neurons
      could be clearly visualized. Time-lapse imaging revealed that: (1) the
      presynaptic varicosities actively moved with marked changes in their shapes, and
      the postsynaptic scaffolding protein gephyrin clusters underwent coordinated
      movements in a tight association with the presynaptic varicosities, (2) the
      extents of morphological changes and movements depended on the developmental
      stages, reaching a stable level as the inhibitory synaptic connections matured,
      and (3) the motility indexes of the varicosity and its counterpart gephyrin
      cluster were well correlated. Furthermore, action potential blockade with
      tetrodotoxin treatment reduced the varicosity size, gephyrin cluster mobility as
      well as the amplitude of GABAergic synaptic currents in pyramidal neurons. Such a
      neural activity-dependent dynamic change in GABAergic synaptic morphology is
      likely to play a critical role in the regulatory mechanism underlying the
      formation and plasticity of inhibitory synapses.

PMID- 22146685
TI  - Structure of plantaricin locus of Lactobacillus plantarum 8P-A3.
AB  - Lactobacillus plantarum 8P-A3 is a strain which is well known on the Russian
      pharmaceutical market and it is included in several probiotic products. The
      strain has been widely used since 1973 but the mechanisms of its antibacterial
      activity were unknown. L. plantarum 8P-A3 expressed high antagonistic activity
      against the wide range of bacterial pathogens including Streptococcus agalactiae,
      Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Pseudomonas
      aeruginosa and Klebsiella pneumoniae strains. DNA sequence analysis of L.
      plantarum 8P-A3 genome revealed the presence of a complete plantaricin locus of
      about 20,000 bp encoding genes of at least two bacteriocins--plantaricins EF and
      NC8. The plantaricin locus found in L. plantarum 8P-A3 is homologous to the
      plantaricin cluster in L. plantarum J51.

PMID- 22146686
TI  - Bacterial diversity in Philippine fermented mustard (burong mustasa) as revealed
      by 16S rRNA gene analysis.
AB  - Previous studies on the bacterial profile of burong mustasa, a traditional
      Philippine fermented food, had been conducted using culture-dependent techniques.
      Since these methods may underestimate the total microbiota of a sample, a culture
      independent study was done to determine the bacterial diversity in burong mustasa
      through molecular biology techniques. Bacterial DNA was isolated from fermented
      mustard samples at different stages of fermentation. The isolated genomic DNA was
      amplified by PCR using specific primers for the 16S ribosomal RNA gene (16S
      rDNA). The 1.5 kb amplicons obtained were subjected to nested PCR using primers
      for the internal variable region of the 16S rDNA. The 585 bp nested PCR amplicons
      were then subjected to denaturing gradient gel electrophoresis (DGGE) to separate
      the different bacteria present in each sample. Distinct and unique bands in the
      DGGE profile were excised, reamplified, purified and sequenced for bacterial
      identification. Molecular cloning of the 1.5 kb 16S rDNA was also performed using
      the pGEM-T Easy Vector System. The cloned gene was sequenced for bacterial
      identification. The identified microbiota in burong mustasa at different stages
      of fermentation include lactic acid bacteria and several uncultured bacteria
      (initial up to the final stages); acetic acid bacteria (middle stage); and
      Streptobacillus and Fusobacterium species (initial stage). The potential
      probiotic bacteria found in burong mustasa are Weissella and Lactobacillus.

PMID- 22146687
TI  - Assessment of bacterial diversity in selected Philippine fermented food products
      through PCR-DGGE.
AB  - The bacterial population in several Philippine fermented food preparations was
      assessed by PCR-denaturing gradient gel electrophoresis (PCR-DGGE) of the 16S
      rRNA gene (16S rDNA). Genomic DNA was isolated directly from alamang (fermented
      shrimp paste), burong isda (fermented fish and rice), burong hipon (fermented
      shrimp and rice), burong mustasa (fermented mustard leaves), tuba (sugar cane
      wine), suka (vinegar) and sinamak (spiced vinegar) using one of two protocols,
      namely - MoBio DNA Extraction Kit procedure and a cetyltrimethylammonium bromide
      based method. Samples recalcitrant to both methods underwent enrichment in three
      culture broths prior to DNA isolation. Isolated DNA was amplified using nested
      primer pairs targeting the bacterial 16S rDNA. PCR products were subjected to
      DGGE to elucidate the bacterial diversity in each fermented food. 16S rDNA
      sequence analyses revealed that lactic acid bacteria (LAB) and acetic acid
      bacteria (AAB) were dominant in the food samples. The LAB identified were
      Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus panis,
      Lactobacillus pontis and Weissella cibaria. Identified AAB were Acetobacter
      pomorum, Acetobacter ghanensis, Acetobacter orientalis, and Acetobacter
      pasteurianus. Among these, L. fermentum, L. plantarum and W. cibaria are
      established probiotic bacteria, while L. panis and L. pontis are potential
      probiotic bacteria. This finding would increase the appeal and significance of
      local fermented foods to consumers. Furthermore, the majority of the identified
      bacteria in the study have not been reported before in culture-dependent studies
      of similar food preparations. As such, some of the bacterial 16S rDNA obtained
      were cloned to have an initial partial bacterial 16S rDNA library for Philippine
      fermented foods.

PMID- 22146688
TI  - Probiotic bacterial strains differentially modulate macrophage cytokine
      production in a strain-dependent and cell subset-specific manner.
AB  - Gut mucosal macrophages play a pivotal role in driving mucosal immune responses,
      resulting in either activation of inflammatory immune responses to pathogenic
      challenge or tolerance to beneficial luminal contents such as food and commensal
      bacteria. Macrophage responses elicited are dependent on tissue environment and
      the resulting cell subset, where homeostatic macrophages resemble the M2
      macrophage subset and inflammatory macrophages resemble M1s. Probiotics can
      modulate macrophage function with outcome dependent on subset present. Using a
      THP-1 monocyte cell line-derived model of CD14high/low M1 and M2 macrophages, the
      aim of this study was to investigate the immunomodulatory effects of a panel of
      heat-killed probiotic bacteria and their secreted proteins on the subset-specific
      inflammatory marker profile of TNFalpha, IL-6 and NFkappaB. M1 and M2 cells were
      generated by differentiation of monocyte stable transfectants for high and low
      CD14 expression with phorbol 12-myristate 13-acetate and vitamin D3,
      respectively, where the resulting CD14lo M2 and CD14hi M1s mimicked homeostatic
      and inflammatory mucosal macrophages. Subsets were stimulated by enteropathic
      lipopolysaccharides in the presence or absence of heat-killed (HK) or secreted
      proteins (SP) from a panel of probiotic bacteria. Regulation of cytokine
      expression was measured by ELISA and NFkappaB activity by reporter assay. HK
      probiotics suppress CD14lo and augment CD14hi M1 and M2 production of TNFalpha
      whereas SPs augmented CD14hi M1 TNFalpha and were generally suppressive in the
      other subtypes. M2 macrophage IL-6 production was suppressed by both HK and SPs
      and differentially regulated in CD14lo and CD14hi M1s. NFkappaB activation failed
      to parallel the regulatory profiles for TNFalpha and IL-6 which is suggestive of
      probiotic bacteria exerting their regulatory effects on these cytokines in an
      NFkappaB-independent manner. In conclusion, HK and SP probiotics differentially
      regulate macrophage cytokines and NFkappaB activation in a subset-dependent
      manner and suggest a cautionary approach to probiotic treatment of mucosal
      inflammation.

PMID- 22146689
TI  - The impact of meals on a probiotic during transit through a model of the human
      upper gastrointestinal tract.
AB  - Commercial literature on various probiotic products suggests that they can be
      taken before meals, during meals or after meals or even without meals. This has
      led to serious confusion for the industry and the consumer. The objective of our
      study was to examine the impact of the time of administration with respect to
      mealtime and the impact of the buffering capacity of the food on the survival of
      probiotic microbes during gastrointestinal transit. We used an in vitro Digestive
      System (IViDiS) model of the upper gastrointestinal tract to examine the survival
      of a commercial multi-strain probiotic, ProtecFlor(r). This product, in a capsule
      form, contains four different microbes: two lactobacilli (Lactobacillus
      helveticus R0052 and Lactobacillus rhamnosus R0011), Bifidobacterium longum R0175
      and Saccharomyces cerevisiae boulardii. Enumeration during and after transit of
      the stomach and duodenal models showed that survival of all the bacteria in the
      product was best when given with a meal or 30 minutes before a meal (cooked
      oatmeal with milk). Probiotics given 30 minutes after the meal did not survive in
      high numbers. Survival in milk with 1% milk fat and oatmeal-milk gruel were
      significantly better than apple juice or spring water. S. boulardii was not
      affected by time of meal or the buffering capacity of the meal. The protein
      content of the meal was probably not as important for the survival of the
      bacteria as the fat content. We conclude that ideally, non-enteric coated
      bacterial probiotic products should be taken with or just prior to a meal
      containing some fats.

PMID- 22146690
TI  - Prebiotics to manage the microbial control of energy homeostasis.
AB  - The prevalence of obesity is continuously growing and has reached epidemic
      proportions. It is clear that current methods to combat obesity are not effective
      enough to reduce the problem. Therefore, further investigation is needed to
      develop new strategies. Recent research pointed out a potential role of the
      microbial community associated to the human host in controlling and influencing
      the energy homeostasis. According to the concept of Gastrointestinal Resource
      Management, this microbiota and its metabolic potential can be steered with the
      aim of improving host health. This review therefore focuses on the modulation of
      the intestinal microbiota through prebiotics with the aim to control several
      aspects of metabolic homeostasis. In a first part, the importance of host-microbe
      cross-talk at the intestinal epithelium is discussed. Yet, energy metabolism,
      which includes both lipid and glucose metabolism, is also regulated by several
      key organs including the adipose tissue, brain, liver, muscles, pancreas and gut.
      Therefore, in a second part, we will discuss the microbial factors that are
      involved in the communication between these different tissues, and their
      potential management. Finally, we will give some future prospects of the use of
      prebiotics in an individualised treatment of metabolic disorders.

PMID- 22146691
TI  - A comprehensive post-market review of studies on a probiotic product containing
      Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011.
AB  - The probiotic preparation Lacidofil(r) has been commercially available in Europe,
      Asia and North America since 1995. This product is a combination of two strains,
      Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011. The strains
      have been evaluated for safety, identity and mechanisms of probiotic action in
      vitro, in animal models and human clinical trials. The strains adhered to human
      epithelial cells, helped to maintain the barrier function and blocked the
      adhesion of a number of pathogens, allowing them to be cleared from the
      intestine. The strains also elicited an anti-inflammatory response by down
      regulating IL-1beta, IL-8 and TNF-alpha. In various stress models, the probiotic
      combination facilitated better coping and outcomes which may be through the
      maintenance of barrier function and suppressing inflammation. Overall, pre
      clinical studies suggest a potential anti-infectious role for the strains and the
      combination. Clinical studies, primarily in children, have identified Lacidofil
      as an effective supplement for various gastrointestinal diseases such as
      antibiotic-associated diarrhoea and acute gastroenteritis. Recent research has
      also indicated that Lacidofil may be beneficial for individuals with atopic
      dermatitis or vaginal dysbacteriosis.

PMID- 22146692
TI  - Antibiotic susceptibility of different lactic acid bacteria strains.
AB  - Five lactic acid bacteria (LAB) strains belonging to species Lactobacillus
      acidophilus, Lactobacillus helveticus, Lactobacillus delbrueckii subsp.
      bulgaricus, Lactobacillus delbrueckii subsp. lactis and Streptococcus
      thermophilus were tested for their susceptibility to 27 antibiotics. The minimum
      inhibitory concentrations of each antimicrobial were determined using a
      microdilution test. Among the strains a high susceptibility was detected for most
      of the cell-wall synthesis inhibitors (penicillins, cefoxitin and vancomycin) and
      resistance toward inhibitors of DNA synthesis (trimethoprim/sulfonamides and
      fluoroquinolones). Generally, the Lactobacillus strains were inhibited by
      antibiotics such as chloramphenicol, erythromycin and tetracycline at breakpoint
      levels lower or equal to the levels defined by the European Food Safety
      Authority. Despite the very similar profile of S. thermophilus LC201 to
      lactobacilli, the detection of resistance toward erythromycin necessitates the
      performance of additional tests in order to prove the absence of transferable
      resistance genes.

PMID- 22146693
TI  - Determination of the chiral structure of [Formula: see text] using anomalous x
      ray scattering near the Cs K absorption edge.
AB  - A structural study of [Formula: see text], grown from aqueous solution, was
      performed using anomalous x-ray scattering near the Cs K absorption edge to
      determine an absolute configuration of constituent atoms. The sense of the
      helical structure of the [Formula: see text] chain was found to be predominantly
      right-handed through a comparison of observed Bragg Bijvoet ratios with
      calculated ones. Assuming that [Formula: see text] consists of the two domains
      (i.e. right- and left-handed helices), we estimate that the volume fraction for
      the right-handed helix is [Formula: see text].

PMID- 22146696
TI  - Hop bitter acids exhibit anti-fibrogenic effects on hepatic stellate cells in
      vitro.
AB  - Female inflorescences of the hop plant Humulus lupulus L. contain a variety of
      secondary metabolites with bitter acids (BA) as quantitatively dominating
      secondary metabolites. The use of hops in beer brewing has a long history due to
      the antibacterial effects of the BA and their typical bitter taste. Furthermore,
      hop cones are used in traditional medicine and for pharmaceutical purposes.
      Recent studies indicate that BA may affect activity of the transcription factor
      NFkappaB. NFkappaB plays a key role in the activation process of hepatic stellate
      cells (HSC), which is the key event of hepatic fibrosis. The aim of this study
      was to investigate the effect of BA on HSC (activation) and their potential to
      inhibit molecular processes involved in the pathogenesis of hepatic fibrosis. HSC
      were isolated from murine and human liver tissue and incubated with a
      characterized fraction of bitter acids purified from a CO(2) hop extract. At a
      concentration of 25MUg/ml BA started to induce LDH leakage. Already at lower
      concentrations BA lead to a dose dependent inhibition of HSC proliferation and
      inhibited IkappaB-alpha-phosphorylation, nuclear p65 translocation and binding
      activity in a dose dependent way (up to 10MUg/ml). Accordingly, the same BA-doses
      inhibited the expression of pro-inflammatory and NFkappaB regulated genes as MCP
      1 and RANTES, but did not affect expression of genes not related to NFkappaB
      signaling. In addition to the effect on activated HSC, BA inhibited the in vitro
      activation process of freshly isolated HSC as evidenced by delayed expression of
      collagen I and alpha-SMA mRNA and protein. Together, these findings indicate that
      BA inhibit NFkappaB activation, and herewith the activation and development of
      profibrogenic phenotype of HSC. Thus, bitter acids appear as potential functional
      nutrients for the prevention or treatment hepatic fibrosis in chronic liver
      disease.

PMID- 22146697
TI  - Year in review 2010: Critical Care--Cardiac arrest and cardiopulmonary
      resuscitation.
AB  - This review will summarize some of the data published in 2010 and focus on papers
      published in Critical Care in regard to cardiac arrest and cardiopulmonary
      resuscitation. In particular, we discuss the latest research in therapeutic
      hypothermia after cardiac arrest, including methods of inducing hypothermia,
      potential protective mechanisms, spontaneous hypothermia versus therapeutic
      hypothermia, and several predictors of outcome. Furthermore, we will discuss the
      effects of bystander-initiated cardiopulmonary resuscitation (CPR) in patients
      with physician-assisted advanced cardiac life support, the role of hypercapnea in
      near-death experiences during cardiac arrest, markers of endothelial injury and
      endothelial repair after CPR, and the prognostic value of cell-free plasma DNA as
      a marker of poor outcome after cardiac arrest.

PMID- 22146698
TI  - Repeated resveratrol administration confers lasting protection against neuronal
      damage but induces dose-related alterations of behavioral impairments after
      global ischemia.
AB  - Resveratrol, a naturally occurring polyphenol, has been shown to protect the
      heart and brain against ischemic injury. The current study investigated the
      effects of administration with either a 1 or 10-mg/kg dose of resveratrol on CA1
      neuronal injury and behavioral/cognitive impairments after 10-min global ischemia
      in rats. The open-field, eight-arm radial maze and object recognition tests
      served to evaluate effects of resveratrol treatment on ischemia-induced locomotor
      activity, and spatial and recognition memory impairments, respectively. CA1 and
      CA3 neuronal injury was assessed upon completion of behavioral testing, 85 days
      postischemia. A separate series of groups served to assess neuronal injury at 7
      days postischemia. Global ischemia (10 min) led to approximately 50% CA1 cell
      injury, which was prevented at both short (7 days) and long (85 days)
      postischemic intervals by resveratrol treatment. Importantly, despite comparable
      neuronal protection, the two resveratrol doses showed distinct behavioral
      effects. Thus, the 10-mg/kg resveratrol dose led to an enhanced locomotor
      activity in the open-field 4-days postischemia and an impaired spatial memory in
      the delayed nonmatching to sample and delayed matching to sample radial-maze
      tasks initiated on day 13 postischemia. These findings suggest independent
      actions of resveratrol on distinct physiological systems mediating cellular
      survival and functional recovery and dose-related actions of the polyphenol on
      behavioral and memory processes.

PMID- 22146699
TI  - Lactose as a carrier for inhalation products: breathing new life into an old
      carrier. Preface.

PMID- 22146701
TI  - Three ferritin subunits involved in immune defense from bay scallop Argopecten
      irradians.
AB  - Ferritin is a ubiquitous protein that plays an important role in iron storage and
      iron-withholding strategy of innate immunity. In this study, three genes encoding
      different ferritin subunits were cloned from bay scallop Argopecten irradians
      (AiFer1, AiFer2 and AiFer3) by rapid amplification of cDNA ends (RACE) approaches
      based on the known ESTs. The open reading frames of the three ferritins are of
      516 bp, 522 bp and 519 bp, encoding 171,173 and 172 amino acids, respectively.
      All the AiFers contain a putative Iron Regulatory Element (IRE) in their 5'
      untranslated regions. The deduced amino acid sequences of AiFers possess both the
      ferroxidase center of mammalian H ferritin and the iron nucleation site of
      mammalian L ferritin. Gene structure study revealed two distinct structured genes
      encoding a ferritin subunit (AiFer3). Quantitative real-time PCR analysis
      indicated the significant up-regulation of AiFers in hemocytes after challenged
      with Listonella anguillarum, though the magnitudes of AiFer1 and AiFer2 were much
      higher than that of AiFer3. Taken together, these results suggest that AiFers are
      likely to play roles in both iron storage and innate immune defense against
      microbial infections.

PMID- 22146700
TI  - A peptidoglycan recognition protein from Sciaenops ocellatus is a zinc amidase
      and a bactericide with a substrate range limited to Gram-positive bacteria.
AB  - Peptidoglycan recognition proteins (PGRPs) are a family of innate immune
      molecules that recognize bacterial peptidoglycan. PGRPs are highly conserved in
      invertebrates and vertebrates including fish. However, the biological function of
      teleost PGRP remains largely uninvestigated. In this study, we identified a PGRP
      homologue, SoPGLYRP-2, from red drum (Sciaenops ocellatus) and analyzed its
      activity and potential function. The deduced amino acid sequence of SoPGLYRP-2 is
      composed of 482 residues and shares 46-94% overall identities with known fish
      PGRPs. SoPGLYRP-2 contains at the C-terminus a single zinc amidase domain with
      conserved residues that form the catalytic site. Quantitative RT-PCR analysis
      detected SoPGLYRP-2 expression in multiple tissues, with the highest expression
      occurring in liver and the lowest expression occurring in brain. Experimental
      bacterial infection upregulated SoPGLYRP-2 expression in kidney, spleen, and
      liver in time-dependent manners. To examine the biological activity of SoPGLYRP
      2, purified recombinant proteins representing the intact SoPGLYRP-2 (rSoPGLYRP-2)
      and the amidase domain (rSoPGLYRP-AD) were prepared from Escherichia coli.
      Subsequent analysis showed that rSoPGLYRP-2 and rSoPGLYRP-AD (i) exhibited
      comparable Zn(2+)-dependent peptidoglycan-lytic activity and were able to
      recognize and bind to live bacterial cells, (ii) possessed bactericidal effect
      against Gram-positive bacteria and slight bacteriostatic effect against Gram
      negative bacteria, (iii) were able to block bacterial infection into host cells.
      These results indicate that SoPGLYRP-2 is a zinc-dependent amidase and a
      bactericide that targets preferentially at Gram-positive bacteria, and that
      SoPGLYRP-2 is likely to play a role in host innate immune defense during
      bacterial infection.

PMID- 22146702
TI  - Down-regulation of heme oxygenase-1 by SVCV infection.
AB  - Heme oxygenase (HO-1) is a cytoprotective enzyme that plays a critical role in
      defending the body against oxidant-induced injury during inflammatory processes.
      In mammalian systems, viral infection or antigen expression can down-regulate the
      expression of HO-1. In turn, the induction of HO-1 or overexpression of HO-1
      results in potent and direct antiviral activity that targets the replication of
      several mammalian viruses. In this study, the HO-1 gene of Cyprinus carpio was
      cloned, and the expression profile of HO-1 was investigated during spring viremia
      of carp virus (SVCV) infection. The results demonstrate that the expression of HO
      1 was down-regulated during SVCV infection in the EPC cells and in common carp.
      These results indicated that SVCV infection could induce host oxidative stress,
      which may contribute to tissue injury in affect fish.

PMID- 22146703
TI  - Preservation of human tear protein structure and function by a novel contact lens
      multipurpose solution containing protein-stabilizing agents.
AB  - OBJECTIVES: Tear film proteins have antimicrobial and other functions that may be
      lost after denaturation during contact lens wear. A new multipurpose solution has
      recently become available (Biotrue, Bausch + Lomb Inc., Rochester, NY), which
      contains protein-stabilizing agents including hyaluronic acid, poloxamine, and
      sulfobetaine 10, the latter used previously as a laboratory tool to renature
      proteins. We examine whether this new multipurpose solution formulation can
      prevent the denaturation of human lactoferrin and lysozyme at physiologic levels
      in response to a powerful denaturing challenge. METHODS: Human lactoferrin and
      lysozyme were treated with sodium dodecyl sulfate (SDS) either with or without an
      investigational version of the new multipurpose solution (without its two
      disinfectant agents) (investigational multipurpose solution [iMPS]). The
      structure was assessed by native-polyacrylamide gel electrophoresis (PAGE),
      differential scanning calorimetry (DSC), and fluorometry; additionally,
      antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus
      was measured. RESULTS: The iMPS prevented an SDS-induced shift in the native-PAGE
      banding position of lactoferrin. The SDS treatment substantially altered the
      lactoferrin DSC and fluorescence spectra, indicating that the protein had
      denatured. This change did not occur in the presence of iMPS. Lactoferrin and
      lysozyme showed antibacterial and bacteriolytic activity, which was abolished
      after SDS treatment; this loss of activity did not occur for proteins treated
      with iMPS. CONCLUSIONS: These data clearly show that the iMPS prevents the
      denaturation of physiologic levels of human lactoferrin and lysozyme by the
      strongly denaturing surfactant SDS and that stabilized proteins retain their
      function. We conclude that this solution has the capacity to stabilize the
      structure and function of tear proteins.

PMID- 22146704
TI  - Contact lens-induced circumlimbal staining in silicone hydrogel contact lenses
      worn on a daily wear basis.
AB  - OBJECTIVES: The principal objective of the study was to measure the conjunctival
      staining produced in the circumlimbal region by silicone hydrogel contact lenses
      with different edge designs. The secondary objective was to investigate the
      association between circumlimbal staining and comfort. METHODS: Four silicone
      hydrogel contact lenses: ACUVUE OASYS (knife edge design), AIR OPTIX, Biofinity
      (chisel edge rounded edge combination), and PureVision (rounded edge design), and
      1 hydrogel contact lens, ACUVUE 2 (knife edge design), were tested. The study was
      conducted on a cohort population of 27 established soft contact lens wearers, who
      wore each contact lens type, in a random order, for a period of 10 (+/-2) days.
      Circumlimbal staining was measured in a double-masked fashion through image
      analysis of digital photographs of lissamine green taken under controlled
      experimental conditions. RESULTS: The results obtained showed that contact lens
      edge design was the primary factor controlling circumlimbal staining for silicone
      hydrogel lenses: a rounded edge away from the ocular surface produced the lowest
      staining (average, 0.19%) and a knife edge in close apposition to the ocular
      surface produced the highest staining (average, 1.34%). Contact lens material
      rigidity was also identified to affect circumlimbal staining and an inverse
      association between circumlimbal staining and contact lens comfort was
      demonstrated: the rounded edge design produced the lowest comfort (72 of 100) and
      the knife edge design produced the highest (87 out of 100). CONCLUSION: Soft
      contact lens wear induces circumlimbal staining, the level of staining being
      influenced by the contact lens edge design. However, high level of circumlimbal
      staining is not associated with decreased comfort.

PMID- 22146705
TI  - Avoidant personality problems--their association with somatic and mental health,
      lifestyle, and social network. A community-based study.
AB  - AIM: The aim of the study was to explore the associations between the presence of
      avoidant personality problems (APPs) and 5 areas of impairment: demography,
      somatic issues, mental health, lifestyle, and social issues. METHODS: Avoidant
      personality problem was defined by confirmation of the 2 avoidant personality
      disorder items of the Iowa Personality Disorder Screen and and the Social Phobia
      Inventory (SPIN) short version (MINI-SPIN) screening assessment for generalized
      social anxiety disorder sum score of 6 or more. The questionnaires were
      administered in a Norwegian population survey (the Oslo Health Study-HUBRO).
      Cases consisted of 280 individuals with APP and 5 randomly selected controls
      without APP (n = 1400). RESULTS: The APP group more frequently reported living
      alone, lower level of education, and lower income than controls. Poor self-rated
      health, presence of somatic disease, muscular pain, frequent use of analgesics,
      and visits at a general practitioner were significantly more common in the APP
      group than among controls. The APP group had significantly higher proportion of
      caseness of mental distress, low general self-efficacy, and insomnia, and this
      result held up in multivariate analyses. The APP group showed statistically
      significant higher proportions of physical inactivity, obesity, daily smoking,
      and alcohol problems compared with controls. As for social impairment, a
      significantly higher proportion of the APP group reported "not having enough good
      friends," "high powerlessness," and low community activism, and the 2 former
      variables held up in multivariate analyses. CONCLUSION: In this population-based
      study, we found that high levels of APP, defined closely to avoidant personality
      disorder, were significantly associated with demographic, somatic, and mental
      impairment; low general self-efficacy; and insomnia affecting work ability. In
      addition, APP showed associations with negative lifestyle, alcohol problems, and
      social impairment reporting lack of good friends and lack of empowerment.
      Avoidant personality problem is associated with clinically significant impairment
      in several areas, which underlines the importance of recognizing these problems
      in primary health care.

PMID- 22146706
TI  - Pressure dependence of the melting temperature of rare-gas solids.
AB  - According to Lindemann's law and the Debye model and with the assumption that the
      volume derivative [Formula: see text] of the Gruineisen parameter [Formula: see
      text] is a constant depending on the material, we present a new expression for
      the analysis of the experimental data for the melting temperature of solids under
      a high pressure. The test on rare-gas solids (Ne, Ar, Kr and Xe) shows that the
      calculated results are in good agreement with the corresponding experimental
      data.

PMID- 22146707
TI  - Production of multi-fiber modifying enzyme from Mamillisphaeria sp. for refining
      of recycled paper pulp.
AB  - Enzymatic modification of pulp is receiving increasing interest for energy
      reduction at the refining step of the paper-making process. In this study, the
      production of a multi-fiber modifying enzyme from Mamillisphaeria sp. BCC8893 was
      optimized in submerged fermentation using a response-surface methodology. Maximal
      production was obtained in a complex medium comprising wheat bran, soybean, and
      rice bran supplemented with yeast extract at pH 6.0 and a harvest time of 7 d,
      resulting in 9.2 IU/mL of carboxymethyl cellulase (CMCase), 14.9 IU/mL of filter
      paper activity (FPase), and 242.7 IU/mL of xylanase. Treatment of old corrugated
      container pulp at 0.2-0.3 IU of CMCase/g of pulp led to reductions in refining
      energy of 8.5-14.8%. The major physical properties were retained, including
      tensile and compression strength. Proteomic analysis showed that the enzyme was a
      complex composite of endo-glucanases, cellobiohydrolases, beta-1,4-xylanases, and
      beta-glucanases belonging to various glycosyl hydrolase families, suggestive of
      cooperative enzyme action in fiber modification, providing the basis for refining
      efficiency.

PMID- 22146709
TI  - Inhibitory effects of whisky polyphenols on melanogenesis in mouse B16 melanoma
      cells.
AB  - Whisky exerts an inhibitory effect on melanogenesis in B16 cells, the anti
      melanogenic activity being positively correlated with the aging period and anti
      oxidative activity of whisky. We examined the correlation between the inhibition
      of melanogenesis and the concentration of each compound in various whiskies to
      evaluate the importance of 11 different whisky polyphenols, including ellagic
      acid, gallic acid and lyoniresinol, in the anti-melanogenic activity of whisky.
      The concentration of all the compounds was positively correlated with the anti
      melanogenic activity of whisky. Ellagic acid, gallic acid and lyoniresinol were
      the predominant polyphenols in the whiskies measured by HPLC. These three
      compounds also significantly inhibited the melanogenesis and tyrosinase activity
      in B16 cells. Ellagic acid, gallic acid and lyoniresinol were confirmed as the
      major participants in the anti-melanogenic activity of whisky.

PMID- 22146708
TI  - Coffee and caffeine improve insulin sensitivity and glucose tolerance in C57BL/6J
      mice fed a high-fat diet.
AB  - We have previously demonstrated that coffee and caffeine ameliorated
      hyperglycemia in spontaneously diabetic KK-A(y) mice. This present study
      evaluates the antidiabetic effects of coffee and caffeine on high-fat-diet
      induced impaired glucose tolerance in C57BL/6J mice. C57BL/6J mice fed a high-fat
      diet were given regular drinking water (control group), or a 2.5-fold-diluted
      coffee or caffeine solution (200 mg/L) for 17 weeks. The ingestion of coffee or
      caffeine improved glucose tolerance, insulin sensitivity, and hyperinsulinemia
      when compared with mice in the control group. The adipose tissue mRNA levels of
      inflammatory adipocytokines (MCP-1 and IL-6) and the liver mRNA levels of genes
      related to fatty acid synthesis were lower in the coffee and caffeine groups than
      those in the control group. These results suggest that coffee and caffeine
      exerted an ameliorative effect on high-fat-diet-induced impaired glucose
      tolerance by improving insulin sensitivity. This effect might be attributable in
      part to the reduction of inflammatory adipocytokine expression.

PMID- 22146710
TI  - Effect of Vaccinium ashei reade leaf extracts on lipid metabolism in obese OLETF
      rats.
AB  - The effects of a hot water extract and fractional extracts from rabbiteye
      blueberry (Vaccinium ashei reade) leaves (BBL) on lipid metabolism were studied
      in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Feeding the hot water
      extract and fractional extracts from BBL alleviated hepatic triglyceride
      accumulation in the rats. Additionally, feeding with the flavonol glycoside (FG)
      and proanthocyanidin (PA) fractions lowered serum cholesterol levels in the obese
      rats. The results from measurements of the hepatic enzyme activity indicate that
      the hypolipidemic effects of the hot water extract and the PA fraction might be
      attributable to enhanced lipolysis in the liver. The reduced serum levels of C
      reactive protein, an inflammatory cytokine, by the chlorogenic acid + rutin
      fraction and FG fraction might be associated with alleviating the metabolic
      abnormalities in obese rats. These results indicate that the BBL extracts, and
      especially FG and PA, exerted hypolipidemic effects on obese OLETF rats and
      suggest that an infusion of BBL can be useful as a dietary hypolipidemic
      component.

PMID- 22146712
TI  - Intake of dried bonito broth flavored with dextrin solution induced conditioned
      place preference in mice.
AB  - We investigated to determine whether dried bonito broth flavor induces a
      reinforcing effect using the conditioned place preference (CPP) test. Only dried
      bonito broth did not induce CPP. Sucrose induced CPP in 20% solution. A 21.86%
      dextrin solution, with the same calorie content as the 20% sucrose solution, did
      not induce CPP, but a dextrin solution flavored with dried bonito broth (BD)
      induced CPP. An AD solution containing the same concentrations of dextrin, NaCl,
      IMP, GMP, and amino acids as found in BD tended to increase the time spent in the
      conditioned box but did not significantly. Aromatic compounds, such as citral,
      vanillin, and menthol flavored AD solutions did not induce CPP, whereas an AD
      solution supplemented with dried bonito flavoring agent induced CPP. In mice with
      transected olfactory nerves, CPP was not induced by voluntary intake of BD. These
      results suggest that the aromatic profile of the dried bonito broth plays an
      important role in BD-induced CPP.

PMID- 22146711
TI  - Methionine and serine synergistically suppress hyperhomocysteinemia induced by
      choline deficiency, but not by guanidinoacetic acid, in rats fed a low casein
      diet.
AB  - The effects of dietary supplementation with 0.5% methionine, 2.5% serine, or both
      on hyperhomocysteinemia induced by deprivation of dietary choline or by dietary
      addition of 0.5% guanidinoacetic acid (GAA) were investigated in rats fed a 10%
      casein diet. Hyperhomocysteinemia induced by choline deprivation was not
      suppressed by methionine alone and was only partially suppressed by serine alone,
      whereas it was completely suppressed by a combination of methionine and serine,
      suggesting a synergistic effect of methionine and serine. Fatty liver was also
      completely prevented by the combination of methionine and serine. Compared with
      methionine alone, the combination of methionine and serine decreased hepatic S
      adenosylhomocysteine and homocysteine concentrations and increased hepatic
      betaine and serine concentrations and betaine-homocysteine S-methyltransferase
      activity. GAA-induced hyperhomocysteinemia was partially suppressed by methionine
      alone, but no interacting effect of methionine and serine was detected. In
      contrast, GAA-induced fatty liver was completely prevented by the combination of
      methionine and serine. These results indicate that a combination of methionine
      and serine is effective in suppressing both hyperhomocysteinemia and fatty liver
      induced by choline deprivation, and that methionine alone is effective in
      suppressing GAA-induced hyperhomocysteinemia partially.

PMID- 22146713
TI  - Function and structure studies of GH family 31 and 97 alpha-glycosidases.
AB  - A huge number of glycoside hydrolases are classified into the glycoside hydrolase
      family (GH family) based on their amino-acid sequence similarity. The glycoside
      hydrolases acting on alpha-glucosidic linkage are in GH family 4, 13, 15, 31, 63,
      97, and 122. This review deals mainly with findings on GH family 31 and 97
      enzymes. Research on two GH family 31 enzymes is described: clarification of the
      substrate recognition of Escherichia coli alpha-xylosidase, and glycosynthase
      derived from Schizosaccharomyces pombe alpha-glucosidase. GH family 97 is an
      aberrant GH family, containing inverting and retaining glycoside hydrolases. The
      inverting enzyme in GH family 97 displays significant similarity to retaining
      alpha-glycosidases, including GH family 97 retaining alpha-glycosidase, but the
      inverting enzyme has no catalytic nucleophile residue. It appears that a
      catalytic nucleophile has been eliminated during the molecular evolution in the
      same way as a man-made nucleophile mutant enzyme, which catalyzes the inverting
      reaction, as in glycosynthase and chemical rescue.

PMID- 22146714
TI  - Encapsulation of citral isomers in extracted lemongrass oil with cyclodextrins:
      molecular modeling and physicochemical characterizations.
AB  - The complexation between two isomers of citral in lemongrass oil and varying
      types of cyclodextrins (CDs), alpha-CD, beta-CD, and HP-beta-CD, were studied by
      molecular modeling and physicochemical characterization. The results obtained
      revealed that the most favorable complex formation governing between citrals in
      lemongrass oil and CDs were found at a 1:2 mole ratio for all CDs. Complex
      formation between E-citral and CD was more favorable than between Z-citral and
      CD. The thermal stability of the inclusion complex was observed compared to the
      citral in the lemongrass oil. The release time course of citral from the
      inclusion complex was the diffusion control, and it correlated well with Avrami's
      equation. The release rate constants of the E- and Z-citral inclusion complexes
      at 50  degrees C, 50% RH were observed at 1.32*10(-2) h(-1) and 1.43*10(-2) h(-1)
      respectively.

PMID- 22146715
TI  - Cloning and heterologous expression of the vibrioferrin biosynthetic gene cluster
      from a marine metagenomic library.
AB  - A biosynthetic gene cluster of siderophore consisting of five open reading frames
      (ORFs) was cloned by functional screening of a metagenomic library constructed
      from tidal-flat sediment. Expression of the cloned biosynthetic genes in
      Escherichia coli led to the production of vibrioferrin, a siderophore originally
      reported for the marine bacterium Vibrio parahaemolyticus. To the best of our
      knowledge, this is the first example of heterologous production of a siderophore
      by biosynthetic genes cloned from a metagenomic library. The cloned cluster was
      one of the largest of the clusters obtained by functional screening. In this
      study, we demonstrated and extended the possibility of function-based metagenomic
      research.

PMID- 22146716
TI  - Effect of environmental conditions on the alpha-glucosidase inhibitory activity
      of mulberry leaves.
AB  - Mulberry leaves have been used as the sole food for silkworms in sericulture, and
      also as a traditional medicine for diabetes prevention. Mulberry leaf components,
      for example 1-deoxynojirimycin (1-DNJ), inhibit the activity of alpha-glucosidase
      and prevent increased blood glucose levels, and they are highly toxic to
      caterpillars other than silkworms. The alpha-glucosidase inhibitory activity of
      mulberry leaves changes with the season, but it is unknown which environmental
      conditions influence the alpha-glucosidase inhibitory activity. We investigated
      in this study the relationship between the alpha-glucosidase inhibitory activity
      and environmental conditions of temperature and photoperiod. The results
      demonstrate that low temperatures induced decreasing alpha-glucosidase inhibitory
      activity, while the induction of newly grown shoots by the scission of branches
      induced increasing alpha-glucosidase inhibitory activity. These results suggest
      that the alpha-glucosidase inhibitory activity was related to the defense
      mechanism of mulberry plants against insect herbivores.

PMID- 22146717
TI  - Tobacco salicylic acid glucosyltransferase is active toward tuberonic acid (12
      hydroxyjasmonic acid) and is induced by mechanical wounding stress.
AB  - Recently we reported that rice salicylic acid (SA) glucosyltransferase (OsSGT) is
      active toward 12-hydroxyjasmonic acid (tuberonic acid, TA) and that OsSGT gene
      expression is induced by wounding stress. Here we report that tobacco SA
      glucosyltransferase (NtSGT), which is thought to be an ortholog of OsSGT, is also
      active toward TA. Although NtSGT expression is known to be induced by biotrophic
      stress, it was also induced by wounding stress in the same manner as OsSGT. These
      results indicate that this glucosyltransferase is important not only in
      biotrophic stress but also for wounding stress. It was found that this enzyme is
      dually functional, with activity both toward TA and SA.

PMID- 22146718
TI  - Antioxidant properties of ethyl vanillin in vitro and in vivo.
AB  - We systematically evaluated the antioxidant activity of ethyl vanillin, a
      vanillin analog, as compared with the activities of vanillin and other vanillin
      analogs using multiple assay systems. Ethyl vanillin and vanillin exerted
      stronger antioxidant effects than did vanillyl alcohol or vanillic acid in the
      oxygen radical absorbance capacity (ORAC) assay, although the antioxidant
      activities of vanillyl alcohol and vanillic acid were clearly superior to those
      of ethyl vanillin and vanillin in the three model radical assays. The antioxidant
      activity of ethyl vanillin was much stronger than that of vanillin in the
      oxidative hemolysis inhibition assay, but was the same as that of vanillin in the
      ORAC assay. Oral administration of ethyl vanillin to mice increased the
      concentration of ethyl vanillic acid, and effectively raised antioxidant activity
      in the plasma as compared to the effect of vanillin. These data suggest that the
      antioxidant activity of ethyl vanillin might be more beneficial than has been
      thought in daily health practice.

PMID- 22146719
TI  - Membrane-integrated fermentation system for improving the optical purity of D
      lactic acid produced during continuous fermentation.
AB  - This report describes the production of highly optically pure D-lactic acid by
      the continuous fermentation of Sporolactobacillus laevolacticus and S. inulinus,
      using a membrane-integrated fermentation (MFR) system. The optical purity of D
      lactic acid produced by the continuous fermentation system was greater than that
      produced by batch fermentation; the maximum value for the optical purity of D
      lactic acid reached 99.8% enantiomeric excess by continuous fermentation when S.
      leavolacticus was used. The volumetric productivity of the optically pure D
      lactic acid was about 12 g/L/h, this being approximately 11-fold higher than that
      obtained by batch fermentation. An enzymatic analysis indicated that both S.
      laevolacticus and S. inulinus could convert L-lactic acid to D-lactic acid by
      isomerization after the late-log phase. These results provide evidence for an
      effective bio-process to produce D-lactic acid of greater optical purity than has
      conventionally been achieved to date.

PMID- 22146720
TI  - Inhibition of matrix metalloproteinase-1 induced by oxidative stress in human
      keratinocytes by mangiferin isolated from Anemarrhena asphodeloides.
AB  - Oxidative stress is related to the synthesis of matrix metalloproteinases (MMPs),
      which cause skin aging. The protective effects of mangiferin derived from
      Anemarrhena asphodeloides were investigated against hydrogen peroxide (H(2)O(2))
      induced damage using human skin keratinocyte (HaCaT) cells. Mangiferin was found
      to scavenge intracellular reactive oxygen species (ROS), superoxide radicals, and
      hydroxyl radicals. ROS regulate MMPs gene expression and activation of
      proenzymes. Mangiferin inhibited H(2)O(2)-induced MMP-1 gene expression and
      protein levels as well as its activity. Moreover, it abrogated mitogen-activated
      protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway
      and stress-activated protein kinase/extracellular signal-regulated kinase (SEK)-c
      JUN N-terminal kinase (JNK) pathway, which are induced by H(2)O(2) treatment.
      And, it inhibited DNA binding activity of activator protein-1 (AP-1), a
      transcription factor of MMP-1 and downstream of ERK and JNK. Finally, it
      protected the human skin keratinocytes from H(2)O(2)-induced cell death. Taken
      together, these results indicate that mangiferin attenuated H(2)O(2)-induced MMP
      1 activation via inhibition of ERK and JNK pathway and AP-1.

PMID- 22146721
TI  - Ingested maple syrup evokes a possible liver-protecting effect-physiologic and
      genomic investigations with rats.
AB  - Rats fed a 20%-maple syrup diet (maple syrup group) for 11 d showed significantly
      lower values of the hepatic function markers than those fed a 20%-sugar mix syrup
      diet (control). The reason was suggested by a DNA microarray analysis which
      revealed that the expression of genes for the enzymes of ammonia formation were
      down-regulated in the liver of the maple syrup group.

PMID- 22146722
TI  - Regulation of lipid metabolism by palmitoleate and eicosapentaenoic acid (EPA) in
      mice fed a high-fat diet.
AB  - We investigated whether oral administration of palmitoleate ameliorates disorders
      of lipid metabolism to clarify the effects of one of the components of fish oil.
      Lipid levels in the liver and plasma were significantly decreased by palmitoleate
      and by EPA administration. These results suggest that palmitoleate, in addition
      to EPA, plays a role in the regulation of lipid metabolism by fish oil.

PMID- 22146723
TI  - Systematic localization study on novel proteins encoded by meiotically up
      regulated ORFs in fission yeast.
AB  - We conducted a mitotic localization study on gene products encoded by 56
      uncharacterized fission yeast ORFs that were transcriptionally up-regulated
      during meiotic division. Despite meiotic gene induction, these genes were
      expressed during mitosis as well. Seven gene products were localized in the
      nucleus and/or chromatin; another one was a mitosis-specific spindle pole body
      component and, intriguingly, its human homologue was also localized in the
      centrosome of cultured HeLa cells. Two products appeared to be localized in
      cytoplasmic microtubules, whereas four were mitochondrial proteins. Three other
      proteins were found in the medial ring upon cytokinesis and another was localized
      on the entire cell periphery. The remaining 38 proteins were detected in the
      cytoplasm and showed varied spatial patterns. This systematic study helps our
      integrated understanding of all the protein functions in the fission yeast as a
      eukaryotic model.

PMID- 22146724
TI  - The level of orally ingested vitamin C affected the expression of vitamin C
      transporters and vitamin C accumulation in the livers of ODS rats.
AB  - We investigated the effects of vitamin C administration on vitamin C-specific
      transporters in ODS/ShiJcl-od/od rat livers. The vitamin C-specific transporter
      levels increased in the livers of the rats not administered vitamin C and
      decreased in the livers of those administered vitamin C at 100 mg/d, indicating
      that these transporter levels can be influenced by the amount of vitamin C
      administered.

PMID- 22146725
TI  - Characterization of a loss-of-function mutant of gibberellin biosynthetic gene
      LsGA3ox1 in lettuce.
AB  - A previous study generated lettuce (Lactuca sativa) mutant lines tagged by
      retrotransposon Tnt1 from tobacco (Nicotiana tabacum) and identified a homozygous
      mutant, Tnt6a, that exhibited severe dwarf phenotype. Here we show that Tnt1 is
      inserted into the intron of gibberellin biosynthetic gene LsGA3ox1 in Tnt6a
      mutants. Expression analysis suggests that LsGA3ox1 is nearly knocked out in the
      Tnt6a mutants.

PMID- 22146726
TI  - Characterization of the third glutathione S-transferase gene involved in
      enantioselective cleavage of the beta-aryl ether by Sphingobium sp. strain SYK-6.
AB  - The glutathione S-transferases, LigF and LigE, of Sphingobium sp. strain SYK-6
      respectively play a role in cleavage of the beta-aryl ether of (+)-(betaS)-alpha
      (2-methoxyphenoxy)-beta-hydroxypropiovanillone (MPHPV) and (-)-(betaR)-MPHPV. The
      ligP gene, which showed 59% similarity to ligE at the amino acid level, was
      isolated from SYK-6. LigP produced in Escherichia coli revealed
      enantioselectivity for (-)-(betaR)-MPHPV, and ligE and ligP alone contributed to
      the degradation of (-)-(betaR)-MPHPV in SYK-6.

PMID- 22146727
TI  - Absolute stereochemistry of novel isochromanone derivatives from Leptosphaeria
      sp. KTC 727.
AB  - A novel isochromanone, (S)-8-hydroxy-6-methoxy-4,5-dimethyl-3-methylene
      isochromen-1-one (1), known 2 and previously reported metabolites from
      Leptosphaeria sp. KTC 727 (JCM 13076 = MAFF 239586) were isolated from the same
      source by culturing for a relatively long period. The results of the present
      study disclose their structures involving the absolute stereochemistry. The
      planar structures of these molecules were established by ESIMS and NMR spectral
      analyses. The absolute configuration of 1 was established by comparing its
      electronic circular dichroism (ECD) spectrum with that of structurally-related
      known compound 3. The relative stereochemistry of 2 was revealed by a combination
      of nuclear Overhauser effect (NOE) experiments and thermodynamic discussions.
      Successful transformation of 1 to 2 led us to assign the configuration of 2 after
      comparing their ECD spectra. These compounds exhibited weak antifungal activities
      against Cochliobolus miyabeanus.

PMID- 22146728
TI  - Identification and characterization of a mycobacterial (2R,3R)-2,3-butanediol
      dehydrogenase.
AB  - Bacterial strain B-009, capable of using racemic 1,2-propanediol (PD), was
      identified as a rapid-growing member of the genus Mycobacterium. The strain is
      phylogenetically related to M. gilvum, but has slightly different physiological
      characteristics. An NAD(+)-dependent enantioselective alcohol dehydrogenase,
      which acts on R-PD, was purified from the strain. The enzyme was a homodimer of a
      peptide coded by a 1047-bp gene (mbd1). A highly conserved sequence for medium
      chain dehydrogenase/reductases with a preference for secondary alcohols was found
      in the gene. Hydroxyacetone was produced from R-PD by an enzymatic reaction,
      indicating that position 2 of the substrate was oxidized. The enzyme activity was
      highest for (2R,3R)-2,3-butanediol (R,R-BD), enabling the enzyme to be identified
      as (2R,3R)-2,3-butanediol dehydrogenase (R,R-BD-DH). A homology search revealed
      M. gilvum, M. vanbaalenii, and M. semegmatis to have ORFs similar to mbd1,
      suggesting the widespread distribution of genes encoding R,R-BD-DH among
      mycobacterial strains.

PMID- 22146729
TI  - Photochemical characterization of phytochrome missense mutants.
AB  - Phytochromes are photoreceptors that regulate many aspects of plant growth and
      development in response to red/far-red light signals from the environment. In
      this study, we analyzed chromophore ligation and photochromism of missense
      phytochrome mutants in the Per-Arnt-Sim (PAS)-related domain (PRD). Among the 14
      mutants analyzed, the Gly768Asp mutant of Avena phytochrome A showed aberrant
      photochromism and dark reversion, suggesting that amino acid residues in the C
      terminal domain affect the photochemical properties of the photosensory N
      terminal domain.

PMID- 22146730
TI  - Functional expression and characterization of dipeptidyl peptidase IV from the
      black-bellied hornet Vespa basalis in Sf21 insect cells.
AB  - The maturation of mastoparan B, the major toxin peptide in the venom of Vespa
      basalis, requires enzymatic cleavage of its prosequence presumably via sequential
      liberation of dipeptides. The putative processing enzyme, dipeptidyl peptidase
      IV, was expressed as a glycosylated His-tag fusion protein (rDPP-IV) via the
      baculovirus expression system. rDPP-IV purified by one-step nickel-affinity
      chromatography was verified by Western blot and LC-MS/MS analysis. The
      k(cat)/K(m) of rDPP-IV was determined to be in the range of 10-500 mM(-1).S(-1)
      for five synthetic substrates. The optimal temperature and pH for rDPP-IV were
      determined to be 50  degrees C and pH 9. Enzymatic activity of rDPP-IV was
      significantly reduced by 80 and 60% in the presence of sitagliptin and
      phenylmethylsulfonyl fluoride respectively.

PMID- 22146731
TI  - Evidence of isoprenoid precursor toxicity in Bacillus subtilis.
AB  - The mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways for
      isoprenoid biosynthesis both culminate in the production of the two-five carbon
      prenyl diphosphates: dimethylallyl diphosphate (DMAPP) and isopentenyl
      diphosphate (IPP). These are the building blocks for higher isoprenoids,
      including many that have industrial and pharmaceutical applications. With growing
      interest in producing commercial isoprenoids through microbial engineering,
      reports have appeared of toxicity associated with the accumulation of prenyl
      diphosphates in Escherichia coli expressing a heterologous MVA pathway. Here we
      explored whether similar prenyl diphosphate toxicity, related to MEP pathway
      flux, could also be observed in the bacterium Bacillus subtilis. After genetic
      and metabolic manipulations of the endogenous MEP pathway in B. subtilis,
      measurements of cell growth, MEP pathway flux, and DMAPP contents suggested
      cytotoxicity related to prenyl diphosphate accumulation. These results have
      implications as to understanding the factors impacting isoprenoid biosynthesis in
      microbial systems.

PMID- 22146732
TI  - Antioxidation and tyrosinase inhibition of polyphenolic curcumin analogs.
AB  - A series of polyphenolic curcumin analogs were synthesized and their inhibitory
      effects on mushroom tyrosinase and the inhibition of 1,1-diphenyl-2-picryl
      hydrazyl (DPPH) free radical formation were evaluated. The results indictated
      that the analogs possessing m-diphenols and o-diphenols exhibited more potent
      inhibitory activity on tyrosinase than reference compound rojic acid, and that
      the analogs with o-diphenols exhibited more potent inhibitory activity of DPPH
      free-radical formation than reference compound vitamin C. The inhibition
      kinetics, analyzed by Lineweaver-Burk plots, revealed that compounds B(2) and
      C(2) bearing o-diphenols were non-competitive inhibitors, while compounds B(11)
      and C(11) bearing m-diphenols were competitive inhibitors. In particular,
      representative compounds C(2) and B(11) showed no side effects at a dose of 2,000
      mg/kg in a preliminary evaluation of acute toxicity in mice. These results
      suggest that such polyphenolic curcumin analogs might serve as lead compounds for
      further design of new potential tyrosinase inhibitors.

PMID- 22146734
TI  - Expression of the Arabidopsis borate efflux transporter gene, AtBOR4, in rice
      affects the xylem loading of boron and tolerance to excess boron.
AB  - Boron is an essential nutrient for plants, but it is toxic in excess. Transgenic
      rice plants expressing an Arabidopsis thaliana borate efflux transporter gene,
      AtBOR4, at a low level exhibited increased tolerance to excess boron. Those lines
      with high levels of expression exhibited reduced growth. These findings suggest a
      potential of the borate transporter BOR4 for the generation of high-boron
      tolerant rice.

PMID- 22146733
TI  - Effect of a liver X receptor agonist on deposition and lymphatic absorption of
      plant sterols in stroke-prone spontaneously hypertensive rats having a mutation
      in ATP-binding cassette transporter G5.
AB  - The effects were compared of T0901317, a liver X receptor agonist, on deposition
      in the liver and serum and lymphatic absorption of plant sterols in stroke-prone
      spontaneously hypertensive rats (SHRSPs) having a missense mutation in Abcg5,
      which codes for ATP-binding cassette transporter (ABC) G5, with those in Wistar
      rats. Both strains were pair-fed for 7 d with a 0.5% plant sterol diet with or
      without 5 mg/kg of body weight of T0901317. The deposition of plant sterols in
      the liver and serum was higher in SHRSPs than in Wistar rats. A significant
      reduction of plant sterol deposition was observed in Wistar rats, but not in
      SHRSPs when T0901317 was given. Both strains were then fed for 7 d with a control
      diet with or without T0901317. The lymphatic absorption of plant sterols was
      reduced to almost half the normal level by the T0901317 treatment. However, no
      difference in absorption was apparent between SHRSPs and Wistar rats regardless
      of the T0901317 treatment. These results suggest that the plant sterol deposition
      in SHRSPs was not necessarily caused by the increased absorption of plant
      sterols.

PMID- 22146735
TI  - Enzymatic synthesis of 4-pentulosonate (4-keto-D-pentonate) from D-aldopentose
      and D-pentonate by two different pathways using membrane enzymes of acetic acid
      bacteria.
AB  - 4-Keto-D-arabonate (D-threo-pent-4-ulosonate) and 4-keto-D-ribonate (D-erythro
      pent-4-ulosonate) were prepared from D-arabinose and D-ribose by two successive
      reactions of membrane-bound enzymes, D-aldopentose 4-dehydrogenase and 4-keto-D
      aldopentose 1-dehydrogenase of Gluconobacter suboxydans IFO 12528. Alternatively,
      they were prepared from D-arabonate and D-ribonate with another membrane-bound
      enzyme, D-pentonate 4-dehydrogenase. Analytical data confirmed the chemical
      structures of the 4-pentulosonates prepared. This is the first report of
      successful enzymatic synthesis of 4-pentulosonates.

PMID- 22146736
TI  - Effect of lime pretreatment of brown midrib sorghums.
AB  - The effect of lime pretreatment of brown midrib sorghums on enzymatic
      saccharification was investigated. Under most of the pretreatment conditions, the
      saccharification yields of bmrs were higher than those of the normal
      counterparts. This result suggests that bmr is useful to reduce pretreatment
      costs, because the amount of lime necessary for the pretreatment of biomass can
      reduced by using bmr mutants.

PMID- 22146737
TI  - Ethical principles for physician rating sites.
AB  - During the last 5 years, an ethical debate has emerged, often in public media,
      about the potential positive and negative effects of physician rating sites and
      whether physician rating sites created by insurance companies or government
      agencies are ethical in their current states. Due to the lack of direct evidence
      of physician rating sites' effects on physicians' performance, patient outcomes,
      or the public's trust in health care, most contributions refer to normative
      arguments, hypothetical effects, or indirect evidence. This paper aims, first, to
      structure the ethical debate about the basic concept of physician rating sites:
      allowing patients to rate, comment, and discuss physicians' performance, online
      and visible to everyone. Thus, it provides a more thorough and transparent
      starting point for further discussion and decision making on physician rating
      sites: what should physicians and health policy decision makers take into account
      when discussing the basic concept of physician rating sites and its possible
      implications on the physician-patient relationship? Second, it discusses where
      and how the preexisting evidence from the partly related field of public
      reporting of physician performance can serve as an indicator for specific needs
      of evaluative research in the field of physician rating sites. This paper defines
      the ethical principles of patient welfare, patient autonomy, physician welfare,
      and social justice in the context of physician rating sites. It also outlines
      basic conditions for a fair decision-making process concerning the implementation
      and regulation of physician rating sites, namely, transparency, justification,
      participation, minimization of conflicts of interest, and openness for revision.
      Besides other issues described in this paper, one trade-off presents a special
      challenge and will play an important role when deciding about more- or less
      restrictive physician rating sites regulations: the potential psychological and
      financial harms for physicians that can result from physician rating sites need
      to be contained without limiting the potential benefits for patients with respect
      to health, health literacy, and equity.

PMID- 22146738
TI  - Maternal sepsis, chorioamnionitis, and congenital Candida kefyr infection in
      premature twins.
AB  - This is the first reported case of maternal sepsis and placental transmission of
      Candida kefyr to premature fraternal twins. The mother consumed organic dairy
      products regularly throughout her pregnancy and developed sepsis with
      chorioamnionitis caused by C. kefyr. The twins developed respiratory distress at
      birth. The placenta, fetal membranes, and umbilical cords showed numerous
      colonies of yeasts, subsequently identified as C. kefyr. C. kefyr sepsis in
      preterm neonates should be considered when there is a significant maternal
      history of organic dairy product consumption during pregnancy.

PMID- 22146739
TI  - Epidemiology of invasive Kingella kingae infections in 2 distinct pediatric
      populations cohabiting in one geographic area.
AB  - The annual incidence of invasive Kingella kingae infection in children younger
      than 4 years of age was significantly higher in westernized Jews than in indigent
      Bedouins living side by side in southern Israel (12.21/100,000 and 5.83/100,000,
      respectively, (P < 0.05). One K. kingae clone was overrepresented among isolates
      from Jewish children, suggesting that differences in bacterial pathogenicity may
      contribute to the morbidity excess detected in this population group.

PMID- 22146740
TI  - Pharmacokinetics of nevirapine in HIV and tuberculosis-coinfected children
      receiving antiretroviral fixed-dose combination tablets while receiving
      rifampicin-containing tuberculosis treatment and after rifampicin
      discontinuation.
AB  - We assessed the pharmacokinetics of nevirapine in HIV and tuberculosis-coinfected
      children while they were receiving nevirapine-containing fixed-dose combination
      tablets with rifampicin-based tuberculosis treatment and after discontinuation.
      The median age (range) was 9.7 (4.4-11.7) years. The nevirapine area under the
      concentration versus time curve from 0 to 12 hours and trough concentration with
      rifampicin were 85.3 (40.5-170.7) mg.h/mL and 6.4 (3.00-13.27) mg/mL,
      respectively, providing adequate exposure.

PMID- 22146741
TI  - Central venous catheter repair is associated with an increased risk of bacteremia
      and central line-associated bloodstream infection in pediatric patients.
AB  - BACKGROUND: Repair of broken central venous catheters (CVCs) is common in
      pediatric patients. We hypothesized that this practice predisposes to bacteremia
      and central line-associated bloodstream infections (CLABSI). METHODS: We
      conducted a retrospective case-crossover study of pediatric patients 1 month to
      21 years of age with CVC breakages who underwent a first-time repair at our
      institution, using repair kits provided by CVC manufacturers. We compared rates
      of bacteremia and CLABSI (defined by Centers for Disease Control and Prevention
      criteria) in the 30 days prerepair (control period) and the 30 days postrepair
      (exposure period), with adjustment for within-patient correlation using
      conditional Poisson regression. RESULTS: The mean prerepair rate of bacteremia
      was 9.9 per 1000 catheter-days, which increased to 24.5 postrepair, resulting in
      an adjusted incidence rate ratio (IRR) of 1.87 (95% CI: 1.05-3.33, P = 0.034).
      Risk of CLABSI demonstrated a greater than 2-fold increase (IRR: 2.15, 95% CI:
      1.02-4.53, P = 0.045) when all catheter-days were included, and a 4-fold increase
      when days on antibiotics were excluded (IRR: 4.07, 95% CI: 1.43-11.57, P =
      0.008). CONCLUSIONS: We found that repair of a broken CVC was associated with a 2
      to 4-fold higher risk of developing CLABSI within 30 days of repair in pediatric
      patients. Further studies are needed to determine interventions to reduce this
      risk and to better define the relative merits of CVC repair compared with
      replacement in selected patient populations.

PMID- 22146742
TI  - Immunologic response to oral polio vaccine in human immunodeficiency virus
      infected and uninfected Zimbabwean children.
AB  - BACKGROUND: Poliovirus eradication is dependent on maintaining adequate community
      wide levels of serologic protection. Many African countries with conditions that
      favor continued wild poliovirus propagation also have a high prevalence of
      pediatric human immunodeficiency virus (HIV) infection. Data are limited
      regarding the degree of serologic immunity conferred on HIV-infected children
      after immunization with oral polio vaccine (OPV). METHODS: This was a cross
      sectional study correlating HIV infection and neutralizing antibodies against
      poliovirus serotypes 1, 2, and 3 in 95 Zimbabwean children 2 months to 2 years of
      age, born to HIV-infected mothers, who received OPV according to the national
      schedule. RESULTS: HIV-infected children had significantly lower rates of
      seroconversion to all 3 poliovirus serotypes than HIV-uninfected children (60%,
      67%, and 47% vs. 96%, 100%, and 82%, P = 0.001, 0.0003, and 0.015 for serotypes
      1, 2, and 3 in HIV-infected and uninfected children, respectively, after >=3 OPV
      doses). Among poliovirus seroconverters, HIV-infected children also had
      significantly lower geometric mean titers against serotypes 1 and 2 than HIV
      uninfected children (geometric mean titers: 198 and 317 vs. 1193 and 1056, P =
      0.032 and 0.050, for serotypes 1 and 2, respectively, after >=3 OPV doses). In
      addition, HIV-infected children had significantly higher levels of total IgG and
      significantly lower CD4% and mean weight than HIV-uninfected children. Of note,
      none of the HIV-infected children were receiving antiretroviral therapy, and 71%
      had a CD4% indicating severe immunodeficiency. CONCLUSIONS: Pediatric HIV
      infection is associated with a poor serologic response to OPV, which could pose
      an obstacle to global polio eradication.

PMID- 22146743
TI  - Pentanuclear complexes with unusual structural topologies from the initial use of
      two aliphatic amino-alcohol ligands in Fe chemistry.
AB  - Five novel pentanuclear Fe(3+) clusters with the aliphatic amino-alcohol ligands
      3-amino-1-propanol (Hap) and 2-(hydroxymethyl)piperidine (Hhmpip) [Fe(5)(MU(3)
      Omicron)(2)(L)(4)(O(2)CR)(7)] [L = ap(-), R = Ph (1); L = ap(-), R = C(CH(3))(3)
      (2); L = hmpip(-), R = Ph (3); L = hmpip(-), R = C(CH(3))(3) (4)] and
      [Fe(5)(MU(4)-Omicron)(MU(3)
      Omicron)(O(2)CC(CH(3))(3))(8)(ap)(2)Cl(HO(2)CC(CH(3))(3))] (5) are reported.
      Compounds 1-4 were prepared from reactions of preformed trinuclear Fe(3+)
      clusters with the ligands in a molar ratio 1 : 5 in MeCN (1, 3, 4) or DMF (2),
      whereas compound 5 was prepared from the reaction of FeCl(3) with Hap in the
      presence of HO(2)CC(CH(3))(3) in a molar ratio 1 : 3 : 2 in MeCN. To the best of
      our knowledge, 1-5 are the first examples of Fe(3+) complexes with the ligands
      Hap and Hhmpip. The structures of 1-4 are composed of a quasi-planar [Fe(5)(MU(3)
      O)(2)](11+) core which consists of two vertex-sharing [Fe(3)(MU(3)-O)](7+)
      triangles. The structure of 5 is based on the [Fe(5)(MU(4)-O)(MU(3)-O)](11+)
      core, in which the five Fe(3+) ions adopt a monocapped trigonal pyramidal
      topology. Variable-temperature magnetic susceptibility measurements on powdered
      microcrystalline samples of 1 and 5 revealed the existence of antiferromagnetic
      interactions which led to an S = 5/2 ground state. Mossbauer spectroscopy studies
      on powdered microcrystalline samples of 1 and 5 confirmed that all iron ions of
      both complexes are in the Fe(3+) (S = 5/2) state. The variation of the ligand
      environment in the various iron sites was reflected in their different quadruple
      splitting parameters. At T < 50 K the Mossbauer spectra indicated the onset of
      spin relaxation effects in the time scale of the technique (10(-7)-10(-8) s).

PMID- 22146744
TI  - Stem cells. Stem cells follow the clock.

PMID- 22146745
TI  - Organelle dynamics. Stopping mitochondria in their tracks.

PMID- 22146747
TI  - Cell migration. H2O2 sensing: the missing 'Lynk'.

PMID- 22146746
TI  - Walking to work: roles for class V myosins as cargo transporters.
AB  - Cells use molecular motors, such as myosins, to move, position and segregate
      their organelles. Class V myosins possess biochemical and structural properties
      that should make them ideal actin-based cargo transporters. Indeed, studies show
      that class V myosins function as cargo transporters in yeast, moving a range of
      organelles, such as the vacuole, peroxisomes and secretory vesicles. There is
      also increasing evidence in vertebrate cells that class V myosins not only tether
      organelles to actin but also can serve as short-range, point-to-point organelle
      transporters, usually following long-range, microtubule-dependent organelle
      transport.

PMID- 22146748
TI  - Year in review 2010: Critical Care--Respirology.
AB  - In this review, 21 original papers published last year in the respirology and
      critical care sections of Critical Care are classified and analyzed in the
      following categories: mechanical ventilation, lung recruitment maneuvers, and
      weaning; the role of positive end-expiratory pressure in acute lung injury
      models; animal models of ventilator-induced lung injury; diaphragmatic
      dysfunction; the role of mechanical ventilation in heart-lung interaction; and
      miscellanea.

PMID- 22146749
TI  - Recording of fast activity at the onset of partial seizures: depth EEG vs. scalp
      EEG.
AB  - Rapid discharges (25-80 Hz), a characteristic EEG pattern often recorded at
      seizure onset in partial epilepsies, are often considered as electrophysiological
      signatures of the epileptogenic zone. While the recording of rapid discharges
      from intracranial electrodes has long been established, their observation from
      the scalp is challenging. The prevailing view is that rapid discharges cannot be
      seen clearly (or at all) in scalp EEG because they have low signal-to-noise
      ratio. To date, however, no studies have investigated the 'observability' of
      rapid discharges, i.e. under what conditions and to what extent they can be
      visible in recorded EEG signals. Here, we used a model-based approach to examine
      the impact of several factors (distance to sources, skull conductivity, source
      area, source synchrony, and background activity) on the observability of rapid
      discharges in simultaneously simulated depth EEG and scalp EEG signals. In our
      simulations, the rapid discharge was clearly present in depth EEG signals but
      mostly almost not visible in scalp EEG signals. We identified some of the factors
      that may limit the observability of the rapid discharge on the scalp. Notably,
      surrounding background activity was found to be the most critical factor. The
      findings are discussed in relation to the presurgical evaluation of epilepsy.

PMID- 22146750
TI  - Rearranging the world: neural network supporting the processing of temporal
      connectives.
AB  - Temporal connectives (before/after) give us the freedom to describe a sequence of
      events in different orders. Studies have suggested that 'before-initiating'
      sentences, in which events are expressed in an order inconsistent with their
      actual order of occurrence, might need additional computation(s) during
      comprehension. The results of independent component analysis suggest that these
      computations are supported by a neural network connecting the bilateral caudate
      nucleus with the right middle frontal gyrus, left precentral gyrus, bilateral
      parietal lobule and inferior temporal gyrus. Among those regions, the caudate
      nucleus and the left middle frontal gyrus showed greater activations for 'before'
      than 'after' sentences. The functional network observed in this study may support
      sequence learning and processing in a general sense.

PMID- 22146751
TI  - Measuring venous blood volume changes during activation using hyperoxia.
AB  - This study describes a novel method for measuring relative changes in venous
      cerebral blood volume (CBVv) using hyperoxia as a contrast agent. This method
      exploits the extravascular BOLD effect and its dependency on both task-related
      activation induced changes in venous blood oxygenation and changes due to
      breathing an oxygen enriched gas mixture. Changes in CBVv on activation can be
      estimated by comparing the change in transverse relaxation rate, R2*, due to
      hyperoxia in both baseline and activation states. Furthermore these measurements
      can be converted into a measure of the percentage change in CBVv. Experiments
      were performed to measure changes in a CBVv-weighted signal in response to a
      simple motor task. Both positive and negative changes in CBVv-weighted signal
      were detected in the positively activated BOLD region.

PMID- 22146752
TI  - Striatal activations signal prediction errors on confidence in the absence of
      external feedback.
AB  - Research on the neural bases of learning has mainly focused on reinforcement
      learning where the central role of the dopaminergic system is well established.
      However, in everyday life many decisions are not followed by feedback, in which
      case humans have been shown to code the most probable outcome into memory. We
      used functional magnetic resonance imaging (fMRI) to examine the neural basis of
      internally generated signals on correctness and decision confidence in the
      complete absence of feedback in a categorization task. During test trials after
      observational training activation in dopaminergic target regions was modulated by
      the correctness of the answer similarly as during feedback-based training.
      Moreover, activation in the nucleus accumbens and putamen was correlated with the
      prediction error on confidence as estimated by a reinforcement learning model. In
      this model subjective confidence ratings acquired after each trial served as
      outcome measure. Activation in the striatum therefore follows a similar pattern
      in response to prediction errors on confidence as it does during reinforcement
      learning in response to reward prediction errors, but with respect to internally
      generated signals based on knowledge of the structure of the environment.
      Furthermore, ventral striatal activation decreased with stimulus novelty, which
      might support the allocation of attention to unfamiliar stimuli. These results
      provide a parsimonious account for the neural bases of learning, indicating
      overlapping neural substrates of reinforcement learning and learning when outcome
      information has to be internally constructed.

PMID- 22146753
TI  - Task-specific modulation of effective connectivity during two simple unimanual
      motor tasks: a 122-channel EEG study.
AB  - Neural oscillations are thought to underlie coupling of spatially remote neurons
      and gating of information within the human sensorimotor system. Here we tested
      the hypothesis that different unimanual motor tasks are specifically associated
      with distinct patterns of oscillatory coupling in human sensorimotor cortical
      areas. In 13 healthy, right-handed subjects, we recorded task-induced neural
      activity with 122-channel electroencephalography (EEG) while subjects performed
      fast self-paced extension-flexion movements with the right index finger and an
      isometric contraction of the right forearm. Task-related modulations of inter
      regional coupling within a core motor network comprising the left primary motor
      cortex (M1), lateral premotor cortex (lPM) and supplementary motor area (SMA)
      were then modeled using dynamic causal modeling (DCM). A network model
      postulating coupling both within and across frequencies best captured observed
      spectral responses according to Bayesian model selection. DCM revealed dominant
      coupling within the beta-band (13-30 Hz) between M1 and SMA during isometric
      contraction of the forearm, whereas fast repetitive finger movements were
      characterized by strong coupling within the gamma-band (31-48 Hz) and between the
      theta- (4-7 Hz) and the gamma-band. This coupling pattern was mainly expressed in
      connections from lPM to SMA and from lPM to M1. We infer that human manual motor
      control involves task-specific modulation of inter-regional oscillatory coupling
      both within and across distinct frequency bands. The results highlight the
      potential of DCM to characterize context-specific changes in coupling within
      functional brain networks.

PMID- 22146754
TI  - Incidence and characteristics of far-field R-wave sensing in low right atrial
      septum pacing.
AB  - BACKGROUND: Although low atrial septal (LAS) pacing may prevent atrial
      tachyarrhythmias in selected patients, far-field R-wave (FFRW) sensing in this
      region seems more likely than in the right atrial appendage. METHODS AND RESULTS:
      We compared the clinical characteristics and prevalence of FFRW sensing in 31
      recipients (mean age, 74 +/- 10 years) of dual-chamber pacemakers, randomly
      assigned to 10.0 mm (n=15) vs. 1.1mm (n=16) tip-ring electrode spacing of bipolar
      atrial leads implanted in the LAS for management of bradyarrhythmias. The
      pacemakers were programmed to DDD mode with backup rates at 50-60 beats/min. FFRW
      sensing was measured with atrial sensitivity set at 0.1 mV, and increased in 0.1
      mV steps. Predictors of FFRW sensing were examined by multiple variable
      regression analysis, and hazard ratios (HR) and confidence intervals (CI) were
      calculated. At atrial sensitivities of 0.1 and 0.5 mV, FFRW was sensed in 24
      (77%) and 9 (29%) patients, respectively. A 10.0-mm tip-ring electrode spacing of
      the atrial lead (HR 10.3; 95%CI 1.0-102.7; P=0.047), and presence of left
      ventricular hypertrophy (LVH) on 12-lead ECG (HR 14.5, 95%CI 1.2-180.0; P=0.037)
      were independent predictors of FFRW sensing. CONCLUSIONS: The prevalence of FFRW
      sensing in the LAS region was high. A narrow spacing of the tip-ring electrodes
      is recommended in the LAS, particularly in the presence of LVH on ECG.

PMID- 22146755
TI  - Novel acute collateral flow index in patients with total coronary artery
      occlusion during ST-elevation myocardial infarction.
AB  - BACKGROUND: The effect of collaterals to occluded coronary arteries during ST
      elevation myocardial infarction (STEMI) is unclear. The conventional CVP-based
      formula to calculate collateral flow index during STEMI yields values higher than
      in elective patients, which prompted derivation of a modified formula, pertinent
      in STEMI when left ventricular mean diastolic pressure (LVMDP) is the
      extravascular pressure limiting collateral flow. We aimed to evaluate this new
      LVMDP-based acute collateral flow index (ACFI). METHODS AND RESULTS: The pressure
      distal to coronary artery occlusion (P(d)) was measured during intervention in
      111 consecutive STEMI patients, 67 (61%) of whom underwent primary intervention,
      followed for 58 months. ACFI (0.18 +/- 0.17, median 0.15) correlated with both
      P(d) and collateral grade (P<0.0001). Higher creatine kinase levels and white
      cell counts were measured in the lowest ACFI tertile compared with the highest
      tertile group (P<0.012). ACFI correlated slightly with early regional but not
      with global left ventricular ejection fraction or with long-term coronary events
      and mortality. CONCLUSIONS: The ACFI is appropriate for evaluating collateral
      function during STEMI. Collateral flow during STEMI may marginally limit
      myocardial damage but had no effect on left ventricular contraction or long-term
      mortality, most likely because of the low flow provided by emerging collaterals
      and the high proportion of patients undergoing intervention before the beneficial
      effect of collaterals could be realized.

PMID- 22146756
TI  - Proton-pump inhibitors: the devil or the savior for patients undergoing
      percutaneous coronary intervention?

PMID- 22146757
TI  - Efficacy of clotinab in acute myocardial infarction trial-ST elevation myocardial
      infarction (ECLAT-STEMI).
AB  - BACKGROUND: This study investigated the efficacy and the safety of the upstream
      glycoprotein (Gp) IIb/IIIa inhibitor (clotinab; ISU ABXIS, Seoul, Republic of
      Korea) under 600-mg clopidogrel pretreatment compared with provisional use in ST
      elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 786
      STEMI patients were randomized to upstream use in the emergency room (ER) (n =
      392) or provisional use during percutaneous coronary intervention (PCI) (n =
      394). All patients were prescribed 600-mg clopidogrel in the ER. The primary
      endpoint was the 30-day incidence of composite events including death, nonfatal
      myocardial infarction, target vessel revascularization, and stroke. There was no
      significant difference in the events that occurred in 40 patients (10.2%) in the
      upstream arm and 55 patients (14.0%) in the provisional arm during the 30 days
      (odds ratio 0.70, 95% confidence interval 0.45-1.08). Major bleeding was higher
      in the upstream arm (1.5% vs. 0%, P = 0.02). However, there was a significant
      reduction in 30-day composite events in the upstream arm in the high-risk
      population (Killip class >=II or GRACE score >140). CONCLUSIONS: The upstream use
      of clotinab under a 600-mg clopidogrel loading may not significantly reduce
      cardiac events following primary PCI but may improve the clinical outcome in high
      risk patients.

PMID- 22146758
TI  - Be concise to find the candidate for intensive care: importance of risk
      stratification of ischemic heart disease.

PMID- 22146760
TI  - Transmyocardial drilling revascularization combined with heparinized bFGF
      incorporating stent activates resident cardiac stem cells via SDF-1/CXCR4 axis.
AB  - OBJECTIVE: To investigate whether transmyocardial drilling revascularization
      combined with heparinized basic fibroblast growth factor (bFGF)-incorporating
      degradable stent implantation (TMDRSI) can promote myocardial regeneration after
      acute myocardial infarction (AMI). METHODS: A model of AMI was generated by
      ligating the mid-third of left anterior descending artery (LAD) of miniswine.
      After 6 h, the animals were divided into none-treatment (control) group (n=6) and
      TMDRSI group (n=6). For TMDRSI group, two channels with 3.5 mm in diameter were
      established by a self-made drill in the AMI region, into which a stent was
      implanted. Expression of stromal cell-derived factor-1(alpha) (SDF-1(alpha)) and
      CXC chemokine receptor 4 (CXCR4), cardiac stem cell (CSC)-mediated myocardial
      regeneration, myocardial apoptosis, myocardial viability, and cardiac function
      were assessed at various time-points. RESULTS: Six weeks after the operation,
      CSCs were found to have differentiated into cardiomyocytes to repair the
      infarcted myocardium, and all above indices showed much improvement in the TMDRSI
      group compared with the control group (P<0.001). CONCLUSIONS: The new method has
      shown to be capable of promoting CSCs proliferation and differentiation into
      cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting
      myocardial apoptosis, thereby enhancing myocardial regeneration following AMI and
      improving cardiac function. This may provide a new strategy for myocardial
      regeneration following AMI.

PMID- 22146759
TI  - Soluble multi-trimeric TNF superfamily ligand adjuvants enhance immune responses
      to a HIV-1 Gag DNA vaccine.
AB  - BACKGROUND: DNA vaccines remain an important component of HIV vaccination
      strategies, typically as part of a prime/boost vaccination strategy with viral
      vector or protein boost. A number of DNA prime/viral vector boost vaccines are
      currently being evaluated for both preclinical studies and in Phase I and Phase
      II clinical trials. These vaccines would benefit from molecular adjuvants that
      increase correlates of immunity during the DNA prime. While HIV vaccine immune
      correlates are still not well defined, there are a number of immune assays that
      have been shown to correlate with protection from viral challenge including CD8+
      T cell avidity, antigen-specific proliferation, and polyfunctional cytokine
      secretion. METHODOLOGY AND PRINCIPAL FINDINGS: Recombinant DNA vaccine adjuvants
      composed of a fusion between Surfactant Protein D (SP-D) and either CD40 Ligand
      (CD40L) or GITR Ligand (GITRL) were previously shown to enhance HIV-1 Gag DNA
      vaccines. Here we show that similar fusion constructs composed of the TNF
      superfamily ligands (TNFSFL) 4-1BBL, OX40L, RANKL, LIGHT, CD70, and BAFF can also
      enhanced immune responses to a HIV-1 Gag DNA vaccine. BALB/c mice were vaccinated
      intramuscularly with plasmids expressing secreted Gag and SP-D-TNFSFL fusions.
      Initially, mice were analyzed 2 weeks or 7 weeks following vaccination to
      evaluate the relative efficacy of each SP-D-TNFSFL construct. All SP-D-TNFSFL
      constructs enhanced at least one Gag-specific immune response compared to the
      parent vaccine. Importantly, the constructs SP-D-4-1BBL, SP-D-OX40L, and SP-D
      LIGHT enhanced CD8+ T cell avidity and CD8+/CD4+ T cell proliferation 7 weeks
      post vaccination. These avidity and proliferation data suggest that 4-1BBL,
      OX40L, and LIGHT fusion constructs may be particularly effective as vaccine
      adjuvants. Constructs SP-D-OX40L, SP-D-LIGHT, and SP-D-BAFF enhanced Gag-specific
      IL-2 secretion in memory T cells, suggesting these adjuvants can increase the
      number of self-renewing Gag-specific CD8+ and/or CD4+ T cells. Finally adjuvants
      SP-D-OX40L and SP-D-CD70 increased T(H)1 (IgG2a) but not T(H)2 (IgG1) antibody
      responses in the vaccinated animals. Surprisingly, the B cell-activating protein
      BAFF did not enhance anti-Gag antibody responses when given as an SP-D fusion
      adjuvant, but nonetheless enhanced CD4+ and CD8+ T cell responses. CONCLUSIONS:
      We present evidence that various SP-D-TNFSFL fusion constructs can enhance immune
      responses following DNA vaccination with HIV-1 Gag expression plasmid. These data
      support the continued evaluation of SP-D-TNFSFL fusion proteins as molecular
      adjuvants for DNA and/or viral vector vaccines. Constructs of particular interest
      included SP-D-OX40L, SP-D-4-1BBL, SP-D-LIGHT, and SP-D-CD70. SP-D-BAFF was
      surprisingly effective at enhancing T cell responses, despite its inability to
      enhance anti-Gag antibody secretion.

PMID- 22146762
TI  - A single-crystal neutron scattering study of lattice melting in ferroelastic
      [Formula: see text].
AB  - We present the results of an extensive single-crystal neutron scattering study of
      the ferroelastic phase transition in [Formula: see text]. This material has
      previously been demonstrated to undergo a continuous loss of long-range order at
      its ferroelastic transition, which is the phenomenon known as lattice melting. We
      show that our data are consistent with a special form of lattice melting where
      the long-range order appears to be destroyed in a two-dimensional sense, but is
      preserved in the third dimension.

PMID- 22146761
TI  - ER signaling regulation drives the switch between autophagy and apoptosis in NRK
      52E cells exposed to cisplatin.
AB  - Cisplatin (cisPt) use in chemotherapy is limited by the occurrence of a severe
      nephrotoxicity. Both autophagy and apoptosis seem to contribute in kidney
      response to cisPt, however their cross-talk is still controversial, since the
      role played by autophagy (cytoprotective or harmful) and the cellular site
      driving their switch, are still unclear. Here, we used a multidisciplinary
      approach to study the correlation between autophagy and apoptosis in renal NRK
      52E cells exposed to cisPt. We showed two "sensitivity-thresholds" to cisPt,
      stating whether apoptosis or autophagy would develop: 10 MUM dose of cisPt
      activated autophagy that preserved cell homeostasis; however 3-methyladenine co
      administration affected cell viability and induced apoptosis. In contrast, 50 MUM
      cisPt determined cell death by apoptosis, whereas the pre-conditioning with
      taurine contributed to cell rescue, delaying apoptosis and maintaining autophagy.
      Hence, autophagy protects NRK-52E cells from cisPt injury. By studying the
      expression of ER specific hallmarks, such as GRP78, GRP94 and GADD153/CHOP, we
      found a possible pivotal role of ER signaling modulation in the crosstalk between
      autophagy and apoptosis induced by cisPt. To the best of our knowledge, this is
      the first demonstration that taurine enhances autophagic protection against
      apoptosis by reducing ER stress, thus making it possible to develop new
      strategies to reduce severe cisPt-induced side-effects such as nephrotoxicity.

PMID- 22146763
TI  - Role of circulating free alu DNA in endometrial cancer.
AB  - BACKGROUND: Endometrial cancer (EC) is the most common cancer of the female
      genital tract. However, no screening method for EC has been established yet. In
      this study, we evaluated the cell-free DNA in EC. METHODS: Fifteen healthy
      individuals, 9 with benign gynecologic diseases, and 53 with ECs were included in
      this study. Alu sequences in free DNA fragments were used as surrogate markers,
      and cell-free DNA density was measured by quantitative real-time polymerase chain
      reaction. RESULTS: The cell-free DNA levels in ECs tended to be higher than in
      benign condition (healthy individuals + benign gynecologic diseases, n = 24; P =
      0.095). There was no significant difference in cell-free DNA among stage or
      histological grade of EC, and no significant change in cell-free DNA before and
      after operation (P = 0.25): Moreover, in 19 ECs, cell-free DNA decreased after
      operation, however, in 6 ECs, cell-free DNA did not decrease. Three ECs recurred,
      and cell-free DNA did not decrease in these cases. CONCLUSIONS: Measurement of
      cell-free DNA is not useful for EC screening; however, the change of cell-free
      DNA in a patient may be a prognostic biomarker of EC.

PMID- 22146764
TI  - Outcome and prognostic factors of laparoscopic radical hysterectomy and pelvic
      lymphadenectomy in 148 patients with stage IB1 cervical cancer.
AB  - OBJECTIVE: To evaluate the surgical, oncological outcome and prognostic factors
      of laparoscopic radical hysterectomy (LRH) and pelvic lymphadenectomy in patients
      with stage IB1 cervical cancer. MATERIALS AND METHODS: Patients with IB1 cervical
      cancer undergoing LRH at the First People's Hospital of Foshan between January
      2000 and March 2010 were enrolled in this study. Follow-up data were available.
      RESULTS: A total of 148 patients were identified. One case converted to
      laparotomy. Median number of resected pelvic lymph nodes was 23. Median blood
      loss was 250 mL and median operative time was 257 minutes. Intraoperative and
      postoperative complications occurred in 5.4% and 6.75% patients, respectively.
      Other medical problems included 47 cases (31.75%) of bladder dysfunction. Twenty
      seven patients (18.24%) had microscopic nodal metastasis. A total of 37 patients
      received adjuvant therapy. After a median follow-up of 28 months, 21 patients had
      a recurrence. The overall 5-year survival rate is 82%. Univariate analysis showed
      the factors affecting the survival rate were nonsquamous histologic type, high
      grade, deep cervical stromal invasion, lymphovascular space invasion, and lymph
      node metastasis (P = 0.016, P = 0.045, P = 0.021, P = 0.038, and P = <0.001). The
      Cox proportional hazards regression analysis indicated only lymph node metastasis
      (odds ratio = 6.293, P < 0.001) was an independent poor prognostic factor.
      CONCLUSIONS: Laparoscopic radical hysterectomy can be a safe alternative to
      abdominal RH for patients with IB1 cervical cancer. Lymph node metastasis was an
      independent poor prognostic factor.

PMID- 22146765
TI  - Postoperative chylous ascites in patients with gynecologic malignancies.
AB  - OBJECTIVE: To evaluate the incidence and the effective treatment of postoperative
      chylous ascites in patients with gynecologic malignancies. METHODS: In this
      report, we retrospectively reviewed the cases of 4119 patients who underwent
      pelvic and/or para-aortic lymph node dissection for gynecologic malignancies in
      Fudan University Cancer Hospital. RESULTS: Among these 4119 cases, 7 (0.17%)
      patients had chylous ascites postoperatively. The average age of these patients
      was 52 years. The mean time interval between operation and the appearance of
      chylous ascites was 30 days (range, 5-75 days). The incidence of chylous ascites
      after para-aortic lymphadenectomy was approximately 0.32% (5/1540), whereas the
      rate after pelvic lymphadenectomy alone was 0.077% (2/2579). All cases with
      chylous ascites were resolved by conservative treatment. This included placement
      of a peritoneal drainage tube. The mean time to resolution was 13 days (range, 2
      28 days). None of the cases had recurrent chylous ascites during follow-up.
      CONCLUSIONS: Para-aortic lymph node dissection may be associated with
      postoperative chylous ascites. Patients may have their chylous ascites
      successfully treated with conservative management. An abdominal drainage tube can
      be a simple and effective approach and should be considered in the treatment.

PMID- 22146767
TI  - A single nucleotide polymorphism in EXO1 gene is associated with cervical cancer
      susceptibility in Chinese patients.
AB  - OBJECTIVE: The aim of this study was to investigate the association of
      Exonuclease1 (EXO1) genetic polymorphism and the development of cervical
      carcinoma. METHODS: This study was conducted with 126 patients diagnosed with
      cervical cancer and 278 people with no cancer history. The polymerase chain
      reaction-based restriction fragment length polymorphism was used to evaluate the
      K589E and C908G gene polymorphisms. Unconditional logistic regression analysis
      was used to estimate the association between the genotypes and the risk for
      cervical cancer. RESULTS: This is the first study on the role of EXO1 K589E
      (rs1047840) and EXO1 C908G (rs10802996) polymorphisms in cervical cancer in a
      Chinese population. Our results indicated that the EXO1 K589G polymorphism were
      significantly associated with the risk for cervical cancer. Compared with the G
      allele EXO1 K589E, the A allele increased the risk for cervical cancer (adjusted
      odds ratio, 1.67; 95% confidence interval, 1.13-2.45). By contrast, we have not
      found a significant association between the EXO1 C908G polymorphism and cervical
      cancer risk (P = 0.791). CONCLUSION: These findings indicate that the SNPs of
      EXO1 K589E may contribute to cervical cancer carcinogenesis in Chinese
      populations. A larger population study will need to be carried out to further
      validate the potential association of EXO1 genetic polymorphism and cervical
      carcinoma.

PMID- 22146766
TI  - Intravenous/intraperitoneal paclitaxel and intraperitoneal carboplatin in
      patients with epithelial ovarian, fallopian tube, or peritoneal carcinoma: a
      feasibility study.
AB  - OBJECTIVE: This study aimed to evaluate intravenous (IV)/intraperitoneal (IP)
      paclitaxel and IP carboplatin (TCipTip therapy) feasibility in epithelial ovarian
      (EOC), fallopian tube (FTC), or peritoneal carcinoma (PC) patients. METHODS: From
      December 2007 to August 2010, 20 women with histologically confirmed stage IC to
      IV EOC, FTC, or PC received 6 TCipTip cycles after the primary cytoreductive
      surgery. Intravenous paclitaxel was administered at 135 mg/m followed by IP
      carboplatin based on the area under the curve = 6 on day 1; IP paclitaxel at 60
      mg/m was administered on day 8. The toxicity grade was determined by CTCAE
      version 3.0. The institutional review board requested we reduce the IP paclitaxel
      dose in the first cycle to ensure safety. RESULTS: Twenty women, including 18
      with EOC, 1 with stage IIC FTC, and 1 with stage IV primary PC, received TCipTip
      therapy. There were 12 serous, 5 endometrioid, 1 mucinous, 1 clear cell
      adenocarcinoma, and 1 mixed carcinoma (clear cell and endometrioid) cases. Eleven
      women achieved optimal status at primary surgery. Grade 3/4 hematologic toxicity
      incidence was 73% (neutrocytopenia), 9% (thrombocytopenia), and 24% (anemia).
      Grade 3/4 nonhematologic toxicities were observed in 5 patients (4 with grade 3
      allergy and 1 with grade 3 ileus). Twelve patients (60%) completed more than 6
      chemotherapy cycles. Reasons for interruption included paclitaxel allergy, grade
      2 abdominal pain, carboplatin allergy during the seventh cycle, disease
      progression, pleural embolism, ileus, and address change. CONCLUSIONS: Toxicities
      for TCipTip therapy were acceptable; this therapy is feasible for EOC, FTC, or PC
      patients. Further TCipTip therapy evaluation is warranted.

PMID- 22146768
TI  - The use of retinoids in ovarian cancer: a review of the literature.
AB  - Ovarian cancer is the deadliest of all gynecologic malignancies. The search for
      novel treatment modalities to augment traditional chemotherapy and improve
      quality of life is ongoing. Retinoids, a class of compounds composed of vitamin
      A, its natural derivatives, and synthetic analogs, have been studied extensively
      in both the prevention and treatment of gynecologic malignancies. In this
      article, we reviewed preclinical studies and clinical trials conducted using
      retinoids in ovarian cancer.

PMID- 22146769
TI  - Expression and clinical significance of sperm-associated antigen 9 in patients
      with endometrial carcinoma.
AB  - OBJECTIVE: To investigate the expression and humoral immune response of sperm
      associated antigen 9 (SPAG9) in endometri al carcinoma. METHODS: Sperm-associated
      antigen 9 gene expression levels were evaluated in endometrial carcinoma,
      endometrial hyperplasia, adjacent tissues, and normal endometrial tissues by
      reverse transcriptase-polymerase chain reaction, immunohistochemistry, and
      Western blot. Sperm-associated antigen 9 concentration in serum samples from 10
      healthy women, 20 women with benign diseases, and 50 women with endometrial
      carcinoma was detected by enzyme-linked immunosorbent assay. RESULTS: (1) Sperm
      associated antigen 9 antibodies were detected in approximately 72% of patients
      with endometrial cancer but not in healthy controls. (2) A significant difference
      has been found among pathological types and degrees (P < 0.05), and it was also
      found to be expressed in transferred lymph nodes. (3) Sperm-associated antigen 9
      serum concentration (ng/mL) of patients with endometrial carcinoma is
      significantly higher than those of the healthy group (P < 0.05). Patients
      harboring grade 3 endometrial carcinoma were found to have significantly higher
      SPAG9 concentrations than those of grade 1/grade 2 (P = 0.003). CONCLUSIONS:
      SPAG9 is positively expressed in endometrial cancer, and with a high humoral
      immune response in patients. It may serve as a new type of endometrial cancer
      markers for early detection, diagnosis and treatment.

PMID- 22146770
TI  - Tumor necrosis factor alpha -308 G>A polymorphisms and cervical cancer risk: a
      meta-analysis.
AB  - OBJECTIVE: Tumor necrosis factor alpha (TNF-alpha), secreted mainly by activated
      macrophages, is recently involved in fighting against tumorigenesis. Tumor
      necrosis factor alpha -308 G>A, the common polymorphism in the promoter of TNF
      alpha, has been implicated to alter the risk of cervical cancer, yet the results
      of relative studies are inconclusive or controversial. To derive a more precise
      estimation of the relationship, we performed a meta-analysis based on 8 studies.
      METHODS: A comprehensive search was conducted to examine all the eligible studies
      of TNF-alpha -308 G>A polymorphism and cervical cancer risk. We used odds ratios
      (ORs) with 95% confidence intervals (CIs) to assess the strength of the
      association. RESULTS: Eight studies regarding TNF-alpha -308 G>A polymorphism
      status including 2298 cases and 1903 controls were collected. Overall,
      significantly elevated cervical cancer risk was found for A allele versus G
      allele (OR, 1.25; 95% CI, 1.10-1.42), for GA versus GG (OR, 1.33; 95% CI, 1.14
      1.54), and for GA/AA versus GG (OR, 1.31; 95% CI, 1.14-1.52). In the subgroup
      analysis by ethnicity, significantly increased risks were also found among whites
      (for A allele vs G allele: OR, 1.16; 95% CI, 1.00-1.34; for GA vs GG: OR, 1.24;
      95% CI, 1.05-1.48; and for GA/AA vs GG: OR, 1.22; 95% CI, 1.03-1.44) and Asians
      (for A allele vs G allele: OR, 2.36; 95% CI, 1.60-3.50; AA vs GG: OR, 3.85; 95%
      CI, 1.30-11.37; for GA vs GG: OR, 2.06; 95% CI, 1.30-3.27; GA/AA vs GG: OR, 2.29;
      95% CI, 1.49-3.52; and for AA vs GA/GG: OR, 3.70; 95% CI, 1.25-10.81). However,
      no significant associations were found among Africans for all genetic models.
      CONCLUSIONS: The natural genetic polymorphism in TNF-alpha -308 G>A is a risk
      factor for developing cervical cancer, especially for Asians and whites.

PMID- 22146771
TI  - Stage I noninvasive and minimally invasive uterine serous carcinoma:
      comprehensive staging associated with improved survival.
AB  - OBJECTIVE: The aim of this study was to determine if comprehensive surgical
      staging is a better predictor of outcome than incomplete staging for women with
      stage I noninvasive or minimally invasive (<=3 mm) uterine serous carcinoma
      (USC). METHODS: Retrospective chart review was used to identify patients
      undergoing hysterectomy at the Johns Hopkins Hospital from 1989 to 2010. Relevant
      clinical and pathologic data were extracted. Patients with noninvasive and
      minimally invasive (<=3-mm myometrial invasion) USC were identified. Stage was
      assigned based on the 2009 International Federation of Gynecology and Obstetrics
      endometrial cancer criteria. Survival curves were generated using the Kaplan
      Meier method. RESULTS: We identified 63 patients with noninvasive or minimally
      invasive (<=3 mm) USC. Stages I, II, III, and IV disease were noted in 65%
      (41/63), 6% (4/63), 14% (9/63), and 14% (9/63) of the patients, respectively.
      Lower stage was associated with a significantly improved disease-specific
      survival (P = 0.001). Comprehensive staging, including total hysterectomy,
      bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy,
      omentectomy, and peritoneal biopsies, was completed in 29% (12/41) of the
      patients with stage I disease. There were no disease-specific deaths in the
      comprehensive staging group. Compared with incomplete staging, comprehensive
      staging was associated with a significantly improved disease-specific survival (P
      = 0.039). CONCLUSIONS: Patients with stage I noninvasive and minimally invasive
      USC on comprehensive staging have an excellent prognosis. Adjuvant therapy may
      not benefit this patient population.

PMID- 22146772
TI  - Homogeneous bilayer graphene film based flexible transparent conductor.
AB  - Graphene is considered as a promising candidate to replace conventional
      transparent conductors due to its low opacity, high carrier mobility and flexible
      structure. Multi-layer graphene or stacked single layer graphenes have been
      investigated in the past but both have their drawbacks. The uniformity of multi
      layer graphene is still questionable, and single layer graphene stacks require
      many transfer processes to achieve sufficiently low sheet resistance. In this
      work, bilayer graphene film grown with low pressure chemical vapor deposition was
      used as a transparent conductor for the first time. The technique was
      demonstrated to be highly efficient in fabricating a conductive and uniform
      transparent conductor compared to multi-layer or single layer graphene. Four
      transfers of bilayer graphene yielded a transparent conducting film with a sheet
      resistance of 180 Omega(?) at a transmittance of 83%. In addition, bilayer
      graphene films transferred onto the plastic substrate showed remarkable
      robustness against bending, with sheet resistance change less than 15% at 2.14%
      strain, a 20-fold improvement over commercial indium oxide films.

PMID- 22146773
TI  - Oxygen extrusion from amidate ligands to generate terminal Ta=O units under
      reducing conditions. How to successfully use amidate ligands in dinitrogen
      coordination chemistry.
AB  - A series of mixed Cp* amidate tantalum complexes Cp*Ta(RNC(O)R')X(3) (where R =
      Me(2)C(6)H(3), (i)Pr, R' = (t)Bu, Ph, X = Cl, Me) have been prepared via salt
      metathesis and their fundamental reactivities under reducing conditions have been
      explored. Reaction of the tantalum chloro precursors with potassium graphite
      under N(2) or Ar leads to the stereoselective formation of the terminal tantalum
      oxo species, Cp*Ta=O(eta(2)-RN=CR')Cl. This represents the formal extrusion of
      oxygen from the amidate ligand to the reduced tantalum center and is accompanied
      by the formation of the iminoacyl fragment bound to Ta(v). Amidate dinitrogen
      complexes, [Cp*TaCl(RNC(O)(t)Bu)](2)(MU-N(2)) (where R = Me(2)C(6)H(3), (i)Pr)
      were synthesized via salt metathesis from the known [Cp*TaCl(2)](2)(MU-N(2))
      precursor, establishing that amidate ligands can support dinitrogen complexes,
      but not the reduction process often necessary for their synthesis.

PMID- 22146778
TI  - Alzheimer disease: Amyloid-targeting antibody performs well in phase II trial.

PMID- 22146779
TI  - Differences in neuronal activity explain differences in memory forming abilities
      of different populations of Lymnaea stagnalis.
AB  - The ability to learn and form long-term memory (LTM) can enhance an animal's
      fitness, for example, by allowing them to remember predators, food sources or
      conspecific interactions. Here we use the pond snail, Lymnaea stagnalis, to
      assess whether variability between natural populations (i.e., strains) in memory
      forming capabilities correlates with electrophysiological properties at the level
      of a single neuron, RPeD1. RPeD1 is a necessary site of LTM formation of aerial
      respiratory behaviour following operant conditioning. We used strains from two
      small, separate permanent ponds (TC1 and TC2). A comparison of the two
      populations showed that the TC1 strain had enhanced memory forming capabilities.
      Further, the behavioural phenotype of enhanced memory strain was explained, in
      part, by differences in the electrophysiology of RPeD1. Compared to RPeD1 from
      the naive TC2 strain, RPeD1 from the TC1 strain has both a decreased resistance
      and decreased excitability. Moreover, 24h after a single 0.5h training session,
      those membrane properties, as well as the firing and bursting rate, decrease
      further in the TC1 strain but not in the TC2 strain. The initial differences in
      RPeD1 properties in the TC1 strain coupled with their ability to further change
      these properties with a single training session suggests that RPeD1 neurons from
      the TC1 strain are "primed" to rapidly form memory.

PMID- 22146780
TI  - Acupuncture for chemotherapy-induced peripheral neuropathy (CIPN): a pilot study
      using neurography.
AB  - OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) can produce severe
      neurological deficits and neuropathic pain and is a potential reason for
      terminating or suspending chemotherapy treatments. Specific and effective
      curative treatments are lacking. METHODS: A pilot study was conducted to evaluate
      the therapeutic effect of acupuncture on CIPN as measured by changes in nerve
      conduction studies (NCS) in six patients treated with acupuncture for 10 weeks in
      addition to best medical care and five control patients who received the best
      medical care but no specific treatment for CIPN. RESULTS: In five of the six
      patients treated with acupuncture, NCS improved after treatment. In the control
      group, three of five patients did not show any difference in NCS, one patient
      improved and one showed impaired NCS. CONCLUSION: The data suggest that
      acupuncture has a positive effect on CIPN. The encouraging results of this pilot
      study justify a randomised controlled trial of acupuncture in CIPN on the basis
      of NCS.

PMID- 22146781
TI  - The role of real time 3D TEE in defining the anatomy of atrial septal defects and
      modifying the therapeutic approach.

PMID- 22146782
TI  - Use of multi-modality imaging in a patient with a persistent left superior vena
      cava, partial anomalous pulmonary venous connection, and sinus venosus-type
      atrial septal defect.

PMID- 22146783
TI  - Accuracy of 64-multidetector computed tomography coronary angiography in patients
      with symptomatic atrial fibrillation prior to pulmonary vein isolation.
AB  - AIMS: Aim of our study was to investigate the value of multidetector computed
      tomography (MDCT) for detecting significant stenoses of coronary arteries in
      patients with symptomatic atrial fibrillation (AF) prior to pulmonary vein (PV)
      ablation (PVA). BACKGROUND: Many patients undergoing PVA for AF receive three
      dimensional computed tomography or magnetic resonance tomography imaging for
      improving anatomical orientation. METHODS: One-hundred and eighty-one patients
      with AF refractory to antiarrhythmic treatment underwent ECG-gated 64-MDCT for
      identification of PV anatomy and simultaneous assessment of coronary vessels
      before PVA. No additional radiation was incurred for MDCT coronary angiography
      during MDCT scan. Pretest probability for obstructive coronary artery disease
      (CAD) was estimated. Invasive coronary angiography (ICA) was performed in all
      patients with at least intermediate risk of CAD. RESULTS: Eighty-six out of 181
      patients (48%) had ICA and MDCT, 95 patients (52%) underwent MDCT alone. ICA
      revealed significant stenoses in 9% of the catheterized patients (8/86). MDCT
      investigation lead to a sensitivity of 90% (9/10), specificity of 98% (829/844
      lesions), positive predictive value (PPV) of 39% (9/24), and negative predictive
      value (NPV) of 100% (829/830 lesions) for the detection of >50% stenoses seen on
      ICA. All patients with a significant stenosis were classified as patients with
      CAD. Overall prevalence of significant CAD detected by MDCT was found to be low
      with 10% of patients and 2% of all segments. CONCLUSION: MDCT coronary
      angiography is sensitive and highly specific in patients presenting for PVA. In
      this group a negative scan reliably excludes significant CAD. These data suggest
      that MDCT coronary angiography can replace ICA prior to PVA.

PMID- 22146784
TI  - Transoesophageal echocardiographic Doppler colour flow patterns of a normally
      functioning third-generation centrifugal left ventricular assist device.

PMID- 22146785
TI  - Laparoscopic ultralow anterior rectal resection in APPEAR technique for deep
      rectal cancer.

PMID- 22146787
TI  - The impacts of "growing our own": a pilot project to address health disparities
      by training health professionals to become certified diabetes educators in safety
      net practices.
AB  - PURPOSE: The purpose of the study was to examine the impact of incorporating
      certified diabetes educator trainees into medical practices on patient diabetes
      outcomes. METHODS: This was a mixed methods practice-based evaluation study
      undertaken in 2 primary care practices in high-poverty neighborhoods in Buffalo,
      New York. The evaluation entailed a physician-referred patient cohort with pre-
      and postanalysis of chart review data corresponding to the American Diabetes
      Association's diabetes indicators. Patient charts were reviewed at baseline and
      12 months. A brief survey was administered to the providers and staff to
      ascertain the extent to which the certified diabetes educator trainees were
      perceived as useful as part of the medical practice team. RESULTS: Among 74
      patients enrolled in diabetes classes, A1C levels decreased from a mean of 8.8%
      to 8.3%. Among a subset of patients (35%) with poorly controlled diabetes at
      baseline (A1C >= 9), there was a 15% decrease in A1C levels. Overall improvement
      in A1C was observed among 219 patients seen by a diabetes educator, in either a
      diabetes education class or a one-on-one visit. CONCLUSIONS: Results suggest that
      having a certified diabetes educator trainee as part of the primary care practice
      team may advance diabetes care, as evidenced by improvements in glucose control.
      Responses from providers and staff suggest that the certified diabetes educator
      trainees were well integrated into the practices and were perceived as
      instrumental in educating patients to better manage their diabetes.

PMID- 22146786
TI  - Analysis of the seventh edition of American Joint Committee on colon cancer
      staging.
AB  - PURPOSE: The seventh edition of the American Joint Committee on Cancer (AJCC)
      staging system has new substages for colon cancer. We used survival data from a
      single medical center to analyze this new AJCC edition. METHODS: The colon cancer
      database of Taipei Veterans General Hospital provided 1,865 patient records
      covering from 1999 to 2005. Survival rates were evaluated using the Kaplan-Meier
      method. RESULTS: There were 268, 607, 561, and 421 patients in stages I, II, III,
      and IV disease with 5-year observed survival rates of 86.3%, 79.2%, 65.4%, and
      12.8%, respectively. Survival rates were not significantly different between
      those with T4a and T4b disease (P = 0.806). The outcome of N1c disease was
      similar to N1a and N1b but worse than N0 (P = 0.004). Survival rates for M1a and
      M1b disease became different after reclassifying solely peritoneal seeding as M1a
      (P < 0.001). No discrepancy of outcomes between stage IIIA and stage IIB/IIC
      remained in the seventh edition. CONCLUSIONS: Evolution from the fifth to seventh
      edition of the AJCC staging system is successful in separating prognostic groups
      by substaging. But some issues remain unresolved, including the subdivision of
      T4, N1, and M1.

PMID- 22146788
TI  - Self-monitoring of blood glucose: professional advice and daily practice of
      patients with diabetes.
AB  - PURPOSE: This study investigated the advice given by diabetes educators in
      Europe, and the daily practice of Dutch patients with diabetes regarding the use
      of the first or second drop of blood and other aspects concerning self-monitoring
      of blood glucose (SMBG). Method During a diabetes conference in 2009, 96 European
      diabetes educators (including 46 Dutch educators) completed a single-item
      questionnaire about the use of the first or second drop of blood for glucose
      monitoring. A self-reported questionnaire with 20 questions about performing SMBG
      was filled out by 111 patients from an outpatient diabetes clinic of a Dutch
      hospital. RESULTS: Patients were advised to wash their hands with water and soap
      and use the first drop of blood by 89% of the Dutch and 72% of other European
      diabetes educators, while 58% of the patients reported to do this. When the
      patient cannot wash the hands, 85% of the Dutch and 52% of the other European
      educators advised to use the second drop of blood, while 26% of the patients
      reported always using the first drop without washing hands. Always using the side
      of the fingertip and using the lancet once, as advised in guidelines, was
      reported by only 41% and 55% of the patients, respectively. CONCLUSIONS: There is
      no general agreement between professionals regarding the advice on aspects
      concerning SMBG. Patients also reported different acts in daily practice.
      Developing uniform international SMBG guidelines, education, and repeated
      evaluation of the process of collecting an accurate blood sample are needed.

PMID- 22146790
TI  - A giant bladder struvite stone in an adolescent boy.
AB  - A 14-year-old adolescent boy with a history of recurrent lower urinary tract
      infection presented with a complaint of lower abdominal pain. Renal
      ultrasonography revealed bilateral hydronephrosis and X-ray film revealed a huge
      pelvic mass measuring 10 * 8 * 6 cm which filled the whole bladder. Open
      cystolithotomy was performed and magnesium ammonium phosphate (struvite) stone
      weighing 420 g was removed. Although a bladder stone is not rare, in the present
      report, the composition and the huge size of the stone determined in an
      adolescent patient is an interesting clinical entity. To the best of our
      knowledge, this is the largest struvite stone reported in an adolescent patient.

PMID- 22146789
TI  - Racial differences in parents' perceptions of factors important for children to
      live well with diabetes.
AB  - PURPOSE: The purpose of this study is to learn how to serve families with
      children with diabetes in a more culturally effective manner by exploring and
      more fully understanding differences in how white and African American families
      ranked factors they perceived as important to living well with diabetes. METHODS:
      This is a secondary analysis of a survey derived from qualitative and
      quantitative data. A total of 799 parents (84.1% white, 12.3% African American)
      completed the mailed survey. Respondents were asked to rate how much of a
      difference each of 30 survey items makes in a child and family who are living
      well with diabetes, which were placed in rank order by race. Items were combined
      into clinically relevant categories, and mean ratings for each category were
      calculated. Regression analyses were used to test for racial differences between
      items and within categories. RESULTS: The racial groups expressed many similar
      views; however, 2 major themes emerged reflecting racial differences in the
      prioritization of factors affecting the well-being of children with diabetes.
      First, African American families ascribed greater importance to social supports.
      Second, African Americans expressed a preference for interventions that target
      the whole family versus the individual child, whereas whites tended to prefer
      child-centered interventions. CONCLUSION: There is a paucity of research on the
      goals and priorities of pediatric diabetes care from the perspective of parents
      from diverse racial backgrounds. Asking families about the type of care they
      prefer may help to improve the design and delivery of services in a culturally
      competent, effective manner.

PMID- 22146791
TI  - Dural lesions in decompression for lumbar spinal stenosis: incidence, risk
      factors and effect on outcome.
AB  - INTRODUCTION: Decompression for lumbar spinal stenosis is one of the most
      frequent operations on the spine today. The most common complication seems to be
      a peroperative dural lesion. There are few prospective studies on this
      complication regarding incidence and effect on long-term outcome; this is the
      background for the current study. MATERIALS AND METHODS: Swespine, the Swedish
      Spine Register documents the majority (>80%) of lumbar spine operations in Sweden
      today. Within the framework of this register, totally 3,699 operations for spinal
      stenosis during a 5-year period were studied regarding complications and 1-year
      postoperative outcome. Mean patient age was 66 (37-92) years and 44% were males.
      Fourteen percent were smokers and 19% had undergone previous lumbar spine
      surgery. RESULTS: The overall incidence of a peroperative dural lesion was 7.4%,
      8.5% of patients undergoing decompressive surgery only and 5.5% of patients
      undergoing decompressive surgery + fusion (p < 0.001). A logistic regression
      analysis demonstrated that (high) age (p < 0.0004), previous surgery (p < 0.036)
      and smoking (p < 0.049) were significantly predictive factors for dural lesions.
      An odds ratio estimate demonstrated an age-related risk increase with 2.7% per
      year. The risk for dural lesions also increased with number of levels
      decompressed. The 1-year outcome was identical in the two groups with and without
      a dural lesion. CONCLUSION: A dural lesion was seen in 7.4% of decompressive
      operations for spinal stenosis. High age, previous surgery and smoking were risk
      factors for sustaining a lesion, which, however, did not affect the 1-year
      outcome negatively.

PMID- 22146794
TI  - Sources of variation in yolk hormone deposition: consistency, inheritance and
      developmental effects.
AB  - Maternal effects occur when the phenotype of the mother affects the phenotype of
      their offspring. They are thought to have evolved to translate the environmental
      conditions experienced by the mother into adaptive phenotypic variation of the
      offspring. However, the integration of environmental cues allowing adaptive
      responses requires some form of plasticity that depends on the interaction of the
      maternal phenotype and her environment. In birds, maternal yolk hormones
      represent such a pathway for maternal effects, and their adaptive significance
      depends thus on the plasticity in maternal yolk hormone deposition. We studied
      sources of variation in yolk testosterone deposition, focusing on the often
      neglected contribution of the (partly heritable) maternal phenotype. We
      investigated consistency and heritability of yolk testosterone deposition in
      captive canaries of which the F(1) generation was raised in foster nests and
      analyzed the potential effects of the early developmental conditions. We found
      significant female consistency across years in egg mass, yolk mass and total
      amount of yolk testosterone but not in yolk testosterone concentrations. Females
      varied the yolk testosterone concentrations of their eggs across years mainly via
      changes in yolk mass. The heritable variation in egg mass, yolk mass and amount
      of yolk testosterone but not yolk testosterone concentrations was within the
      range of previous studies, but not significantly different from zero. Finally,
      the growth of the daughters as nestling had a significant effect on their yolk
      testosterone deposition at adulthood indicating the transgenerational potential
      for environmental effects - via the effects of yolk hormones on offspring
      development.

PMID- 22146792
TI  - Deciphering the structure and function of FcepsilonRI/mast cell axis in the
      regulation of allergy and anaphylaxis: a functional genomics paradigm.
AB  - Allergy and anaphylaxis are inflammatory disorders caused by immune reactions
      mainly induced by immunoglobulin-E that signal through the high-affinity
      FcepsilonRI receptor to release the inflammatory mediators from innate immune
      cells. The FcepsilonRI/mast cell axis is potently involved in triggering various
      intracellular signaling molecules to induce calcium release from the internal
      stores, induction of transcription factors such as NF-kB, secretion of various
      cytokines as well as lipid mediators, and degranulation, resulting in the
      induction of allergy and anaphylaxis. In this review, we discuss various cellular
      and molecular mechanisms triggered through FcepsilonRI/mast cell axis in allergy
      and anaphylaxis with a special emphasis on the functional genomics paradigm.

PMID- 22146795
TI  - The mRNA expression of cortisol axis related genes differs in Atlantic cod (Gadus
      morhua) categorized as high or low responders.
AB  - Cortisol is a major stress hormone in fish and is known, under normal or
      stressful conditions, to affect several physiological processes including growth
      and immunity. Thus, efforts have been made for several cultured finfish species,
      including the Atlantic cod, to determine whether fish with a high or low cortisol
      response to stress can be identified and selected. However, we have a limited
      understanding of the mechanisms that determine these two phenotypes. Thus, we
      measured total and free plasma cortisol levels in high and low responding cod
      when subjected to a 30 s handling stress, and the mRNA expression of four key
      genes in the glucocorticoid (i.e. cortisol) stress axis both pre- and post
      stress. The cortisol data is consistent with our previous findings for cod, with
      high responding (HR) fish having ~3-fold higher total and free plasma cortisol
      levels when compared to low responding (LR) fish. Three of the transcripts
      studied encode key proteins involved in steroidogenesis (StAR, P450scc and
      3betaHSD), and the constitutive mRNA expression of all three genes was
      significantly higher (~2-fold) in the head kidney of HR fish when compared to LR
      cod. The other gene of interest was the glucocorticoid receptor (GR). We partly
      cloned and characterized a cDNA from Atlantic cod likely to be this fish's
      ortholog of the teleost GR1, and showed that while there was no difference in
      hepatic constitutive GR mRNA expression between groups, HR fish had liver GR mRNA
      levels that were significantly (1.8-fold) higher at 3 h post-stress as compared
      to LR fish. Our results suggest that the different magnitude of cortisol response
      between LR and HR fish is at least partially determined by the capacity of the
      interrenal tissue to produce steroids.

PMID- 22146796
TI  - The CHH-superfamily of multifunctional peptide hormones controlling crustacean
      metabolism, osmoregulation, moulting, and reproduction.
AB  - Apart from providing an up-to-date review of the literature, considerable
      emphasis was placed in this article on the historical development of the field of
      "crustacean eyestalk hormones". A role of the neurosecretory eyestalk structures
      of crustaceans in endocrine regulation was recognized about 80 years ago, but it
      took another half a century until the first peptide hormones were identified.
      Following the identification of crustacean hyperglycaemic hormone (CHH) and moult
      inhibiting hormone (MIH), a large number of homologous peptides have been
      identified to this date. They comprise a family of multifunctional peptides which
      can be divided, according to sequences and precursor structure, into two
      subfamilies, type-I and -II. Recent results on peptide sequences, structure of
      genes and precursors are described here. The best studied biological activities
      include metabolic control, moulting, gonad maturation, ionic and osmotic
      regulation and methyl farnesoate synthesis in mandibular glands. Accordingly, the
      names CHH, MIH, and GIH/VIH (gonad/vitellogenesis-inhibiting hormone), MOIH
      (mandibular organ-inhibiting hormone) were coined. The identification of ITP (ion
      transport peptide) in insects showed, for the first time, that CHH-family
      peptides are not restricted to crustaceans, and data mining has recently inferred
      their occurrence in other ecdysozoan clades as well. The long-held tenet of
      exclusive association with the eyestalk X-organ-sinus gland tract has been
      challenged by the finding of several extra nervous system sites of expression of
      CHH-family peptides. Concerning mode of action and the question of target
      tissues, second messenger mechanisms are discussed, as well as binding sites and
      receptors. Future challenges are highlighted.

PMID- 22146797
TI  - Genotoxicity, acute and subchronic toxicity studies in rats of a rooster comb
      extract rich in sodium hyaluronate.
AB  - The toxicity of a rooster comb extract (IB0004) that contains mainly sodium
      hyaluronate was assessed in acute and subchronic studies and in a bacterial
      reverse mutation assay. In a single dose acute study, male and female rats were
      administered 2000 mg/kg body weight (bw) of the product and observed for 14 days.
      No mortality was recorded, thus it was considered that the minimum lethal dose
      for rats by oral route was greater than 2000 mg/kg bw. A 90-day subchronic study
      (5, 55 and 600 mg/kg bw/day, oral gavage) with 50 male and 50 female Wistar
      Hannover rats produced no significant adverse effects on food consumption, body
      weight, mortality, clinical biochemistry, hematology, gross pathology, and
      histopathology. Although some differences were observed between the treated and
      control animals in body weight gain (%) and some hematological parameters, these
      changes were generally minor in nature and, are considered to be of no
      toxicological significance. The no-observable-adverse-effects level was
      established at 600 mg/kg bw/day. There was no evidence of mutagenic activity in
      Salmonella typhimurium TA98, TA100, TA1535 and TA1537 or in Escherichia coli WP2
      uvra pkM101. In conclusion, the results from these safety studies support the
      safety of rooster comb extract IB0004 in food.

PMID- 22146798
TI  - Determinants of healthcare system's efficiency in OECD countries.
AB  - OBJECTIVE: Firstly, to compare healthcare systems' efficiency (HSE) using two
      models: one incorporating mostly inputs that are considered to be within the
      discretionary control of the healthcare system (i.e., physicians' density,
      inpatient bed density, and health expenditure), and another, including mostly
      inputs beyond healthcare systems' control (i.e., GDP, fruit and vegetables
      consumption, and health expenditure). Secondly, analyze whether institutional
      arrangements, population behavior, and socioeconomic or environmental
      determinants are associated with HSE. DESIGN: Data envelopment analysis (DEA) was
      utilized to calculate OECD countries' HSE. Life expectancy and infant survival
      rate were considered as outputs in both models. Healthcare systems' rankings
      according to the super-efficiency and the cross-efficiency ranking methods were
      used to analyze determinants associated with efficiency. RESULTS: (1) Healthcare
      systems in nine countries with large and stable economies were defined as
      efficient in model I, but were found to be inefficient in model II; (2)
      Gatekeeping and the presence of multiple insurers were associated with a lower
      efficiency; and (3) The association between socioeconomic and environmental
      indicators was found to be ambiguous. CONCLUSIONS: Countries striving to improve
      their HSE should aim to impact population behavior and welfare rather than only
      ensure adequate medical care. In addition, they may consider avoiding specific
      institutional arrangements, namely gatekeeping and the presence of multiple
      insurers. Finally, the ambiguous association found between socioeconomic and
      environmental indicators, and a country's HSE necessitates caution when
      interpreting different ranking techniques in a cross-country efficiency
      evaluation and needs further exploration.

PMID- 22146799
TI  - Ferroelastic domain freezing and low-frequency elastic behaviour of [Formula: see
      text] (ALHS).
AB  - In this work elastic measurements on [Formula: see text] (ALHS) which were
      carried out in the low-frequency range between 1 and 50 Hz are presented. The
      temperature dependence of the inverse elastic compliance [Formula: see text] has
      been determined between 90 K and 420 K. Distinct anomalies have been found in the
      temperature dependence of [Formula: see text], which are connected to the motion
      of domain walls in the ferroelastic phase below [Formula: see text]. Around
      [Formula: see text] a (partial) ferroelastic 'domain freezing' phenomenon has
      been observed. To the knowledge of the authors this is the first time that pure
      ferroelastic domain freezing has been reported. However, below [Formula: see
      text] the domain walls seem to retain a certain vibrational degree of freedom
      which could be responsible for an additional anomaly of the loss modulus which
      was observed.   The elastic behaviour of a crystal of ALHS is dependent on the
      'history' of the given sample. During temperature cycling [Formula: see text]
      shows differences between the first run of heating and cooling and later runs.  
      Finally, some basic insights concerning the domain wall motion were obtained; it
      was found that the domain wall mobility decreases by three orders of magnitude in
      the temperature region 170 - 230 K.

PMID- 22146800
TI  - Interaction studies between photochromic spiropyrans and transition metal
      cations: the curious case of copper.
AB  - A series of four spiropyrans bearing different substituents on the indolic
      nitrogen were synthesized and their capability of binding mono and bivalent
      transition metal cations in solution was assessed via UV-visible absorption
      spectroscopy. All the compounds responded selectively to the presence of Cu(ii)
      ions producing intense absorption bands in the visible region of their spectra.
      Bidimensional (1)H-NMR and MALDI-TOF MS spectroscopies revealed the formation of
      SP dimers mediated by Cu(ii). This is the first example of cross-coupling
      mediated by copper(ii) in mild conditions causing the symmetric dimerization of
      spiropyran dyes.

PMID- 22146801
TI  - Description of International Caenorhabditis elegans Experiment first flight (ICE
      FIRST).
AB  - Traveling, living and working in space is now a reality. The number of people and
      length of time in space is increasing. With new horizons for exploration it
      becomes more important to fully understand and provide countermeasures to the
      effects of the space environment on the human body. In addition, space provides a
      unique laboratory to study how life and physiologic functions adapt from the
      cellular level to that of the entire organism. Caenorhabditis elegans is a
      genetic model organism used to study physiology on Earth. Here we provide a
      description of the rationale, design, methods, and space culture validation of
      the ICE-FIRST payload, which engaged C. elegans researchers from four nations.
      Here we also show C. elegans growth and development proceeds essentially normally
      in a chemically defined liquid medium on board the International Space Station
      (10.9 day round trip). By setting flight constraints first and bringing together
      established C. elegans researchers second, we were able to use minimal stowage
      space to successfully return a total of 53 independent samples, each containing
      more than a hundred individual animals, to investigators within one year of
      experiment concept. We believe that in the future, bringing together individuals
      with knowledge of flight experiment operations, flight hardware, space biology,
      and genetic model organisms should yield similarly successful payloads.

PMID- 22146802
TI  - Inorganic-organic magnetic nanocomposites for use in preventive medicine: a rapid
      and reliable elimination system for cesium.
AB  - PURPOSE: To investigate the potential use of Prussian blue-coated magnetic
      nanoparticles, termed "Prussian blueberry", to bring about the magnetic
      elimination of cesium. METHODS: Prussian blueberry were prepared by a layer-by
      layer assembly method. The morphology, structure and physical properties of the
      Prussian blueberry were investigated as was their ability to magnetically
      eliminate cesium. RESULTS: We confirmed that Prussian blueberry were composed of
      a magnetite nanoparticle-core and a Prussian blue-shell. Under a magnetic field,
      Prussian blueberry (5 mg) reduced the cesium concentration of seawater (3 ml)
      from 150 ppm to about 50 ppm; but regular Prussian blue could not magnetically
      eliminate cesium. Moreover, Prussian blueberry removed a similar proportion of
      cesium from a larger volume of seawater, and from fetal bovine serum and cow's
      milk. CONCLUSIONS: Under a magnetic field, Prussian blueberry was able to rapidly
      eliminate cesium from seawater and from biological matrices such as serum and
      milk.

PMID- 22146805
TI  - Haplo-insufficiency for different genes differentially reduces pathogenicity and
      virulence in a fungal phytopathogen.
AB  - The main determinant of pathogenicity in Ustilago maydis is the b-mating locus,
      where establishment of heterozygosity is sufficient to cause galls/tumors on
      maize plants. However, matings between haploids where one partner contains a
      mutation, in e.g., the smu1 gene, encoding a Ste20-like PAK kinase, often show
      reduced mating and pathogenicity compared to wild type. Here we show that
      similarly, diploids lacking one copy of smu1, are reduced in production of aerial
      hyphae, but do not show significantly-reduced virulence. Haplo-insufficiency was
      also observed for additional genes. UmPde1 is a cyclic phosphodiesterase involved
      in cAMP turnover as part of the cAMP-dependent PKA pathway. Hsl7 plays a role in
      cell length and in the filamentous response to low ammonium in haploid cells.
      Diploids deleted for one copy of either the pde1 or hsl7 genes had reduced or
      increased production of aerial hyphae, respectively, and both were severely
      impaired in virulence compared to wild type diploids. rho1 and pdc1 are two genes
      essential for cell viability in haploids. These genes also displayed haplo
      insufficiency for pathogenesis. rho1/Deltarho1 diploid cells were defective in
      pheromone production and detection, aerial hyphae induction, and were avirulent.
      In contrast, pdc1/Deltapdc1 diploid cells only failed to produce tumors when
      applied to maize whorls. We predict the haplo-insufficiency of most of these
      signaling components is due to stoichiometric imbalance of the respective gene
      products with their interacting partners, thereby impairing virulence-induction
      mechanism(s). Further investigation of the bases for such haplo-insufficiency as
      well as of additional genes displaying this phenotype will provide important
      insights into fundamental aspects of development in this organism as well as
      inter-nuclear communication and genetic control.

PMID- 22146803
TI  - Magnetic nanoparticles enhance adenovirus transduction in vitro and in vivo.
AB  - PURPOSE: Adenoviruses are among the most powerful gene delivery systems. Even if
      they present low potential for oncogenesis, there is still a need for minimizing
      widespread delivery to avoid deleterious reactions. In this study, we
      investigated Magnetofection efficiency to concentrate and guide vectors for an
      improved targeted delivery. METHOD: Magnetic nanoparticles formulations were
      complexed to a replication defective Adenovirus and were used to transduce cells
      both in vitro and in vivo. A new integrated magnetic procedure for cell sorting
      and genetic modification (i-MICST) was also investigated. RESULTS: Magnetic
      nanoparticles enhanced viral transduction efficiency and protein expression in a
      dose-dependent manner. They accelerated the transduction kinetics and allowed non
      permissive cells infection. Magnetofection greatly improved adenovirus-mediated
      DNA delivery in vivo and provided a magnetic targeting. The i-MICST results
      established the efficiency of magnetic nanoparticles assisted viral transduction
      within cell sorting columns. CONCLUSION: The results showed that the combination
      of Magnetofection and Adenoviruses represents a promising strategy for gene
      therapy. Recently, a new integrated method to combine clinically approved
      magnetic cell isolation devices and genetic modification was developed. In this
      study, we validated that magnetic cell separation and adenoviral transduction can
      be accomplished in one reliable integrated and safe system.

PMID- 22146804
TI  - The counterbalanced effect of size and surface properties of chitosan-coated
      poly(isobutylcyanoacrylate) nanoparticles on mucoadhesion due to pluronic F68
      addition.
AB  - PURPOSE: To evaluate of the effect of size and surface characteristics of
      poly(isobutylcyanoacrylate) nanoparticles coated with pluronic F68 and thiolated
      chitosan on mucoadhesion. METHODS: Nanoparticles were obtained by radical
      emulsion polymerization in presence of different amounts of F68 (0-4%w/v).
      Mucoadhesion was ex vivo evaluated by applying nanoparticle suspension on rat
      intestinal mucosa and quantifying the amount of attached nanoparticles after
      incubation. RESULTS: F68 unimers added in the polymerization medium allowed
      decreasing nanoparticle size from 251 to 83 nm, but resulted in nanoparticle
      surface modification. The amount of thiolated chitosan onto nanoparticle surface
      was decreased resulting in lower thiol groups and zeta potential. Consequently,
      the decrease of nanoparticle hydrodynamic diameter resulted in eight-fold
      increase of the number of nanoparticles attached to the mucosa but a significant
      decrease of the weight of attached nanoparticles was observed. This unexpected
      result was due to a decrease of the amount of chitosan and thiolated chitosan
      available to interact with mucus upon addition of F68 in the polymerization
      medium. CONCLUSIONS: Addition of F68 should not be recommended to improve the
      amount of mucoadherent nanoparticles. Further studies could allow understanding
      if the low amount of small size nanoparticles could be able to improve oral
      bioavailability.

PMID- 22146806
TI  - Pain assessment using the Manchester triage system in a Spanish emergency
      department.

PMID- 22146807
TI  - DNA duplexes and triplex-forming oligodeoxynucleotides incorporating modified
      nucleosides forming stable and selective triplexes.
AB  - We have previously reported DNA triplexes containing the unnatural base triad G
      PPI.C3, in which PPI is an indole-fused cytosine derivative incorporated into DNA
      duplexes and C3 is an abasic site in triplex-forming oligonucleotides (TFOs)
      introduced by a propylene linker. In this study, we developed a new unnatural
      base triad A-psi.C(R1) where psi and C(R1) are base moieties 2'
      deoxypseudouridine and 5-substituted deoxycytidine, respectively. We examined
      several electron-withdrawing substituents for R1 and found that 5-bromocytosine
      (C(Br)) could selectively recognize psi. In addition, we developed a new PPI
      derivative, PPI(Me), having a methyl group on the indole ring in order to achieve
      selective triplex formation between DNA duplexes incorporating various Watson
      Crick base pairs, such as T-A, C-G, A-psi, and G-PPI(Me), and TFOs containing T,
      C, C(Br), and C3. We studied the selective triplex formation between these
      duplexes and TFOs using UV-melting and gel mobility shift assays.

PMID- 22146808
TI  - Establishing the mechanism of Rh-catalysed activation of O2 by H2.
AB  - Reductive activation of O(2) by H(2) with rhodium terpyridine complexes in H(2)O
      and CH(3)CN is described and the mechanism is fully elucidated. The rhodium
      complex extracts electrons from H(2) and reductively activates O(2) to form a
      peroxo active intermediate. This intermediate is able to oxidise triphenyl
      phosphine to triphenyl phosphine oxide. A model system constructed in CH(3)CN
      provides isolable analogues of catalytic intermediates in H(2)O, allowing a
      detailed look at each step in the catalytic cycle.

PMID- 22146810
TI  - Plant morphophysiological and anatomical factors associated with nitrous oxide
      flux from wheat (Triticum aestivum).
AB  - Experiments were conducted to study the dynamics of nitrous oxide (N2O) emission
      from wheat varieties viz., Sonalika, HUW 468, HUW 234 and DBW 14 grown in
      alluvial soils of North Bank Plain Agroclimatic Zone of Assam, India. Attempts
      were made to find out the relationship of N2O emission with plant
      morphophysiological, anatomical and soil properties. N2O fluxes from wheat
      varieties ranged from 40 MUg N2O-N m-2 h-1 to 295 MUg N2O-N m-2 h-1. Soil organic
      carbon and soil temperature have shown significant relationship with N2O flux.
      The rate of leaf transpiration recorded from the wheat varieties at different
      growth stages exhibited a positive correlation with N2O emission suggesting that
      movement of N2O along with the transpirational water flow may be an important
      mechanism of N2O transport and emission through wheat plants. Anatomical
      investigation by scanning electron microscope revealed that N2O emission has
      relationship with stomatal frequency of leaf and leaf sheaths. Variety HUW 234
      with the highest stomatal frequency of leaf and leaf sheath also recorded higher
      seasonal N2O emission compared to other varieties. Seasonal N2O emission (E(sif))
      of the varieties ranged from 3.25 to 3.81 kg N2O-N ha-1. Significant variations
      in E(sif) values were recorded within the varieties.

PMID- 22146811
TI  - Adrenaline infiltration in proximal tibial osteotomy: is there evidence for
      safety?

PMID- 22146812
TI  - A comparative study on screw loosening in osteoporotic lumbar spine fusion
      between expandable and conventional pedicle screws.
AB  - INTRODUCTION: The aim of this study is to compare the rate of screw loosening and
      clinical outcomes of expandable pedicle screws (EPS) with those of conventional
      pedicle screws (CPS) in patients treated for spinal stenosis (SS) combined with
      osteoporosis. METHODS: One hundred and fifty-seven consecutive patients with SS
      received either EPS fixation (n = 80) or CPS fixation (n = 77) to obtain
      lumbosacral stabilization. Patients were observed for a minimum of 24 months.
      Outcome measures included screw loosening, fusion rate, Japanese Orthopaedic
      Association (JOA) scores and Oswestry disability index (ODI) scoring system, and
      complications. RESULTS: In the EPS group, 20 screws became loose (4.1%) in 6
      patients (7.5%), and two screws (0.4%) had broken. In the CPS group, 48 screws
      became loose (12.9%) in 15 patients (19.5%), but no screws were broken. The
      fusion rate in the EPS group (92.5%) was significantly higher than that of the
      CPS group (80.5%). The rate of screw loosening in the EPS group (4.1%) was
      significantly lower than that of the CPS group (12.9%). Six EPS (1.8%) screws
      were removed. In the EPS group, two screws had broken but without neural
      complications. Twelve months after surgeries, JOA and ODI scores in the EPS group
      were significantly improved. There were four cases of dural tears, which healed
      after corresponding treatment. CONCLUSIONS: EPS can decrease the risk of screw
      loosening and achieve better fixation strength and clinical results in
      osteoporotic lumbar spine fusion.

PMID- 22146814
TI  - [The construction of the medical writer's authority and legitimacy in late
      imperial China through authorial and allographic prefaces].

PMID- 22146813
TI  - Coincident sequence-specific RNA degradation of linked transgenes in the plant
      genome.
AB  - The expression of transgenes in plant genomes can be inhibited by either
      transcriptional gene silencing or posttranscriptional gene silencing (PTGS).
      Overexpression of the chalcone synthase-A (CHS-A) transgene triggers PTGS of CHS
      A and thus results in loss of flower pigmentation in petunia. We previously
      demonstrated that epigenetic inactivation of CHS-A transgene transcription leads
      to a reversion of the PTGS phenotype. Although neomycin phosphotransferase II
      (nptII), a marker gene co-introduced into the genome with the CHS-A transgene, is
      not normally silenced in petunia, even when CHS-A is silenced, here we found that
      nptII was silenced in a petunia line in which CHS-A PTGS was induced, but not in
      the revertant plants that had no PTGS of CHS-A. Transcriptional activity,
      accumulation of short interfering RNAs, and restoration of mRNA level after
      infection with viruses that had suppressor proteins of gene silencing indicated
      that the mechanism for nptII silencing was posttranscriptional. Read-through
      transcripts of the CHS-A gene toward the nptII gene were detected. Deep
      sequencing analysis revealed a striking difference between the predominant size
      class of small RNAs produced from the read-through transcripts (22 nt) and that
      from the CHS-A RNAs (21 nt). These results implicate the involvement of read
      through transcription and distinct phases of RNA degradation in the coincident
      PTGS of linked transgenes and provide new insights into the destabilization of
      transgene expression.

PMID- 22146815
TI  - Schwannoma of the stomach with elevated preoperative serum carbohydrate antigen
      19-9: report of a case.
AB  - We herein report a case of a gastric schwannoma with elevated preoperative serum
      carbohydrate antigen 19-9 (CA19-9) (155.2 U/ml, normal range 0-36.9 U/ml). A 59
      year-old Japanese man was admitted to our hospital for treatment of a submucosal
      tumor of the stomach detected by barium meal, upper gastrointestinal endoscopy,
      and computed tomography. Endoscopic examination revealed a 3-cm diameter
      submucosal tumor in the antrum of the stomach, but biopsy of the lesion was
      unable to confirm the diagnosis. Positron emission tomography to evaluate the
      malignant potential showed a high uptake of (18)F-fluorodeoxyglucose in the
      tumor. Laparoscopy-assisted distal gastrectomy was therefore performed. The
      histopathological findings of the surgical specimen revealed a benign gastric
      schwannoma, positive for S-100 protein. The postoperative serum CA19-9 levels
      gradually decreased and normalized. To the best of our knowledge, this is the
      first report of a gastric schwannoma with elevated serum CA19-9.

PMID- 22146816
TI  - Trace metal concentrations in tidal flat coastal sediments, Yamaguchi Prefecture,
      southwest Japan.
AB  - Geochemical investigations of tidal flat coastal sediments at Ogori, Ozuki, and
      Kasado in Yamaguchi Bay of southwest Japan were conducted to determine their
      metal concentrations and to assess contamination levels, compared with sediment
      quality guidelines (SQG) and several pollutant indicators. Selected major oxides,
      trace elements, and total sulfur (TS) were determined by X-ray fluorescence. pH
      values of most samples were alkaline, indicating anoxic conditions. Average
      abundances of As, Pb, Zn, Cu, Ni, and Cr in Ozuki sediments were 11, 27, 109, 21,
      19, and 52 mg/kg, respectively, compared to 9, 29, 80, 16, 18, and 42 mg/kg at
      Ogori and 12, 27, 151, 34, 30 and 80 mg/kg at Kasado, respectively. Average
      concentrations of As, Zn, and Cu in all samples and TiO(2), Fe(2)O(3), and
      P(2)O(5) at Kasado were greater than those of the upper continental crust.
      Contamination levels were assessed based on SQG, contamination factors (CF),
      pollution load index (PLI), enrichment factor (EF), and index of geoaccumulation
      (Igeo). According to the SQG of the US EPA, the sediments were heavily polluted
      with respect to As, whereas Zn, Cu, Ni, and Cr were classed as moderately
      polluted. The elevated CF values of As, Pb, and Zn identify moderate to
      considerable contamination, indicating that these metals are potentially toxic in
      the study area. Based on PLI and EF, the study sites are moderate to moderately
      severe polluted with As and Pb, moderately polluted with Zn, and weakly
      contaminated to noncontaminated with Cu, Ni, and Cr. The highest Igeo values for
      As, Pb, and Zn in the surface and core sediments reflected the tendency of metal
      contamination that seems to be related to their fine-grained nature, organic
      matter-rich sediments, and anthropogenic point sources. Trace metal contents were
      strongly correlated with Fe(2)O(3) and TiO(2), suggesting that Fe oxyhydroxides
      and detrital clastic load play a role in controlling abundances in the study
      area.

PMID- 22146817
TI  - A methodology to identify representative configurations of sensors for monitoring
      soil moisture.
AB  - Soil moisture is the key link among hydroecological compartments, responding
      dynamically to sequences of atmospheric processes and management conditions and
      modulating physical, chemical, and biological processes in the soil. Currently,
      there are a variety of monitoring techniques to measure, directly or indirectly,
      the soil moisture. However, some practical issues remain open like the definition
      a priori of the number, location and depth of the monitoring points, and the
      impact of failing or poor performance soil moisture sensors. Here, we present a
      set of techniques, namely Deltatheta time series, wavelet filtering, and time
      stability, to identify representative points and monitoring depths through an
      analysis of hourly soil moisture time series for different configuration of the
      monitoring network. We used real data from a monitoring network consisting of
      seven monitoring points, each one with four EC-5 probes (Decagon Devices Inc.,
      Pullman, WA) at 20, 40, 60, and 100 cm. The use of simple time series of
      Deltatheta allowed us to assess the spatiotemporal influence of the monitoring
      points, while the wavelet periodograms allowed us to get insight about the
      response of the monitoring points at different time scales. Both methods are easy
      to implement or adapt to specific conditions, being coherent to the results
      derived from time stability analysis. For our case study, we concluded that we
      could reallocate 16 sensors (out of 28) without a significant loss of
      information. However, the final decision strongly relies on a deep knowledge of
      the site features and the objectives of the monitoring network.

PMID- 22146818
TI  - Potential effects on the marine environment of dredging of the Bonny channel in
      the Niger Delta.
AB  - This study is an assessment of the possible effects of the dredging project on
      the water quality of the surrounding environment. Water quality data for the
      Bonny offshore river were collected. The parameters assessed were temperature,
      dissolved oxygen (DO), pH, biochemical oxygen demand (BOD), total dissolved
      solids (TDS), total suspended solids (TSS), nitrogen as nitrate, and phosphate.
      The concentrations of TDS, TSS, and nitrate far exceeded the permissible
      standard. There were significant differences between the dry and rainy season
      values of BOD5, TDS, TSS, nitrate, and phosphate. Also, the sediment
      physicochemical analysis indicated the presence of heavy metals such as Pb, Fe,
      Cd, Zn, Cr, and elements such as Ca, K, and Na. Following an assessment of the
      potential impact of the project using interaction matrix and checklist
      questionnaires, results showed that the major physicochemical parameters
      influenced by dredging are DO, TDS, TSS, heavy metals and calcium, potassium, and
      sodium. Mitigation measures for eliminating or reducing the negative impacts of
      dredging are presented.

PMID- 22146819
TI  - Characterization of ionic composition of TSP and PM10 during the Middle Eastern
      Dust (MED) storms in Ahvaz, Iran.
AB  - Because of the recent frequent observations of major dust storms in southwestern
      cities in Iran such as Ahvaz, and the importance of the ionic composition of
      particulate matters regarding their health effects, source apportionment, etc.,
      the present work was conducted aiming at characterizing the ionic composition of
      total suspended particles (TSP) and particles on the order of ~10 MUm or less
      (PM(10)) during dust storms in Ahvaz in April-September 2010. TSP and PM(10)
      samples were collected and their ionic compositions were determined using an ion
      chromatography. Mean concentrations of TSP and PM(10) were 1,481.5 and 1,072.9
      MUg/m(3), respectively. Particle concentrations during the Middle Eastern Dust
      (MED) days were up to four times higher than those in normal days. Ionic
      components contributed to only 9.5% and 11.3% of the total mass of TSP and
      PM(10), respectively. Crustal ions were most abundant during dust days, while
      secondary ions were dominant during non-dust days. Ca(2+)/Na(+) and Cl(-)/Na(+)
      ratios can be considered as the indicators for identification of the MED
      occurrence. It was found that possible chemical forms of NaCl, (NH(4))(2)SO(4),
      KCl, K(2)SO(4), CaCl(2), Ca(NO(3))(2), and CaSO(4) may exist in TSP. Correlation
      between the anionic and cationic components suggests slight anion and cation
      deficiencies in TSP and PM(10) samples, though the deficiencies were negligible.

PMID- 22146820
TI  - Distributions of phthalic esters carried by total suspended particulates in
      Nanjing, China.
AB  - Atmospheric trace phthalic esters (PAEs) carried by total suspended particulates
      were systematically investigated. A total of 450 air samples were collected at
      six typical locations and three specific micro-environmental sites (a stadium
      with a new plastic track, new cars, and a farming greenhouse with plastic film)
      in Nanjing metropolitan area of China from April 2009 to January 2010. The
      samples were analyzed by high-performance liquid chromatography and ultraviolet
      detection. The results are summarized as follows: (1) The dominant PAEs are
      dimethyl phthalate (DMP), dibutyl phthalate (DBP), and diethylhexyl phthalate
      (DEHP), which were found in the atmosphere of Nanjing. The average concentrations
      of DMP, DBP, and DEHP were 10.5 +/- 1.2, 62.3 +/- 4.5, and 33.3 +/- 2.5 ng m(-3),
      respectively, constituting 9.9%, 58.7%, and 31.4% of total PAEs (106 +/- 8.2 ng
      m(-3)). (2) The dynamic variations of atmospheric PAEs in the three specific
      micro-environmental sites showed that the PAE concentrations in the stadium with
      a new plastic track reduced to normal after 1 month remediation, while new cars
      need 6 months to remove their effect. The levels of PAEs in a farming greenhouse
      with plastic film were relatively high, but little PAEs accumulated in
      vegetables. (3) The vertical profiles from 1.5 to 40 m above ground display some
      fluctuations in PAE concentration, but no significant height dependence. This
      information will make a valuable contribution to the examination of the influence
      of atmospheric PAEs on the environment and human health.

PMID- 22146821
TI  - Relevance of the economic crisis in chemical PM10 changes in a semi-arid
      industrial environment.
AB  - This paper shows the changes in PM(10) levels and chemical composition in a
      region in southeast Spain between two periods: September 2005-August 2006 and
      June 2008-May 2009. PM(10) levels in this arid region, with a great number of
      cement, ceramic and related industries, have decreased in the second period in
      concordance with the reduction of industrial production due to the economic
      crisis and the closure of a cement plant. Annual average levels of PM(10)
      decreased from 41 MUg m(-3) in 2005 to 30 MUg m(-3) in 2008 (27%) and to 23 MUg
      m(-3) in 2009 (23%). The relative contribution of the different sources has not
      changed in the area in the latter period and the elements with mineral origin are
      the main components of the PM(10) composition. There is a reduction in the
      concentration of the components that have soil-related industries and crustal
      material resuspension as their main sources, mainly in the case of CO(3) (2-),
      Ca, Sr, Tl and Pb, but the seasonal patterns were the same in both periods. As a
      particular case, there is an uncoupling between the seasonal evolution of SO(2)
      and sulphates in the two study periods, which remarks the existence of a sulphate
      regional background that does not depend on SO(2) local emissions. The decrease
      of V, Ni and Tl levels reflects the reduction of the industrial activity during
      the crisis period, affecting mainly the ceramic sector characterised by a great
      decrease of Tl levels.

PMID- 22146822
TI  - Effect of data pre-treatment procedures on principal component analysis: a case
      study for mangrove surface sediment datasets.
AB  - Principal component analysis (PCA) is capable of handling large sets of data.
      However, lack of consistent method in data pre-treatment and its importance are
      the limitations in PCA applications. This study examined pre-treatments methods
      (log (x + 1) transformation, outlier removal, and granulometric and geochemical
      normalization) on dataset of Mengkabong Lagoon, Sabah, mangrove surface sediment
      at high and low tides. The study revealed that geochemical normalization using Al
      with outliers removal resulted in a better classification of the mangrove surface
      sediment than that outliers removal, granulometric normalization using clay and
      log (x + 1) transformation. PCA output using geochemical normalization with
      outliers removal demonstrated associations between environmental variables and
      tides of mangrove surface sediment, Mengkabong Lagoon, Sabah. The PCA outputs at
      high and low tides also provided to better interpret information about the
      sediment and its controlling factors in the intertidal zone. The study showed
      data pre-treatment method to be a useful procedure to standardize the datasets
      and reducing the influence of outliers.

PMID- 22146824
TI  - Landscape resistance to dispersal: simulating long-term effects of human
      disturbance on a small and isolated wolf population in southwestern Manitoba,
      Canada.
AB  - Landscape fragmentation affects wildlife population viability, in part, through
      the effects it has on individual dispersal. In addition, some forms of human
      disturbance impinge on dispersal without physically fragmenting habitats. Here,
      we use the term "landscape resistance" to capture constraints to dispersal that
      cannot be linked directly to fragmentation. The extent to which landscape
      resistance can influence population persistence is not well understood.
      Agricultural development over the past 60 years has resulted in considerable
      habitat fragmentation in the Riding Mountain National Park (RMNP) region in
      southwestern Manitoba, Canada. We examined how park boundaries, roads outside
      park boundaries and negative human attitudes have altered dispersal success and
      population persistence. We examined whether stochastic disturbance, representing
      infectious disease epidemics, further reduced long-term population persistence
      for various scenarios. Finally, we assessed whether the simultaneous occurrence
      of the three features had additive effects. We simulated dispersal using HexSim,
      a spatially explicit individual-based population model, parameterised with data
      on wolves (Canis lupus) in the RMNP region. Simulations that separately accounted
      for negative human attitudes and roads outside the park boundaries exhibited
      lower mean population size than those that ignored these details. Increasing
      deflection from park boundaries did not appear to have significant impacts. Our
      results did not indicate the presence of additive effects, and scenarios
      incorporating all three features had similar results as that of roads. Stochastic
      disturbance further reduced mean population size. Our results do illustrate how
      less-visible human disturbances (i.e. those that do not clearly alter landscape
      characteristics) can significantly limit dispersal and population persistence.

PMID- 22146825
TI  - Distribution patterns of polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans in sediments of the Xiangjiang River, China.
AB  - We investigated the occurrence and distribution patterns of 2,3,7,8-substituted
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in six sediment
      samples from the Xiangjiang River, Hunan Province, People's Republic of China.
      Total concentrations of PCDD/Fs ranged from 876 to 497,759 (mean 160,766) ng/kg
      dw, the highest of which exceeded that have ever been reported for sediment
      samples. World Health Organization total toxicity equivalent (WHO-TEQ)
      concentrations in three out of six samples were significantly higher than the
      guidance level (21.5 ng WHO-TEQ/kg dw) suggested by Canadian Sediment Quality
      Guideline. A predominance of octachlorodibenzo-p-dioxin (OCDD) was observed with
      an average contribution of 90.8% to the total PCDD/F concentrations, while
      1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) was the major contributor to
      the PCDD/F WHO-TEQ concentrations in most of the sites. Such high levels of OCDD
      and HpCDD may be attributed to the presence of PCP/PCP-Na pollution, although MB
      WW, agricultural straw open burning, and boilers-hazardous wastes were also the
      potential sources of PCDD/Fs. This is the first report for the concentrations and
      congener profiles of PCDD/Fs in sediment samples from the Xiangtan, Zhuzhou, and
      Changsha sections of the Xiangjiang River, providing scientific evidence for
      establishing priorities to reduce ecological risks posed by PCDD/Fs in the
      rapidly developing areas of Hunan Province and elsewhere.

PMID- 22146826
TI  - The pollution and ecological risk of endosulfan in soil of Huai'an city, China.
AB  - Endosulfan, a persistent organic pollutant newly listed under the Stockholm
      Convention, is currently widely produced and used as a pesticide in China.
      Concentrations of endosulfans (including alpha-, beta-isomers, and their
      metabolite endosulfan sulfate) were determined in surface soil collected from
      Huai'an city, where the largest endosulfan producer is located. The
      concentrations of Sigmaendosulfan (sum of alpha-endosulfan, beta-endosulfan, and
      endosulfan sulfate) at all sites ranged from 0.28 to 44.81 ng/g dry weight (dw),
      following a lognormal distribution. The geometric mean was 1.09 ng/g dw, and the
      geometric standard deviation was 3.02. The beta-endosulfan levels were
      consistently greater than those of alpha-isomer. The concentration ratios of
      alpha-endosulfan to beta-endosulfan ranged from 0.03 to 0.70, which were much
      lower than the commercial endosulfan mixture. This is because that alpha
      endosulfan is more volatile and degrades faster than beta-endosulfan in soil. The
      contour map of Sigmaendosulfan levels in soil indicates that the factory was the
      point pollution source with the highest endosulfan level in its surrounding area,
      especially the southern area. However, the non-point agricultural sources are
      more important. Based on Monte Carlo simulation, the Sigmaendosulfan inventory in
      soil in Huai'an is estimated to be 0.8-3.0 tons. In order to understand the
      potential ecological risk of endosulfan, the Monte Carlo-based hazard quotient
      distribution was estimated and showed that Sigmaendosulfan posed a potentially
      high risk to soil organisms. To our knowledge, this study is the first that
      reports soil pollution and risk of endosulfan around the manufacturer in China.
      This study will help China's implementation of Stockholm Convention for the
      reduction and elimination of endosulfan in future.

PMID- 22146827
TI  - High diastereoselectivity in borohydride reductions of coordinated imines.
AB  - Borohydride reduction of the imine groups in a pyruvate-derived cobalt(III)
      complex, (OC-6-33')-[Co(Aim(2)trien)](2)[ZnCl(4)], occurs with high
      diastereoselectivity. The major diastereoisomeric product, (OC-6-33'-ARSSR,CSRRS)
      [Co(A(2)trien)]Cl has been isolated and crystallographically characterised. The
      results from base-induced isomerisation of the major isomer allow us to conclude
      that most of the remaining material from the reduction reactions (consisting of
      minor diastereoisomers) differs from the major isomer only in the relative
      configuration of the coordinated amines. Therefore the initial borohydride attack
      on the imine groups must have occurred predominantly on the same face of each
      imine as that which produces the major isomer. The diastereoselectivity of the
      reaction can be rationalised by proposing hydrogen bonding interactions between
      the incoming hydride reagent and other donor groups in the complex.

PMID- 22146828
TI  - Synthesis of directly linked diazine isosteres of pyrrole-polyamide that
      photochemically cleave DNA.
AB  - A distamycin model containing an isosteric diazine linked pyrrole has been
      designed and synthesized. The key steps of the synthesis involved the successful
      diazotization of the 4-amino-pyrrole derivatives to give the diazomium salts,
      which undergo coupling reactions with N-methylpyrrole to yield the directly
      linked diazine compounds. The amide isosteric-diazine pyrrole I demonstrated
      photo-induced DNA damage upon iradiation with UV light (365 nm).
      Spectrophotometric and mass spectrometric identification suggest that the azo
      linkage in I did not dissociate during irradiation. Moreover, compound I produced
      DNase I footprints with the HexB DNA fragment at AT sites, as well as some other
      mixed sequences (5'-ATGTCG-3'), indicative of the additional role of the diazine
      linkage for interaction at the duplex DNA.

PMID- 22146829
TI  - TCR cross-reactivity and allorecognition: new insights into the immunogenetics of
      allorecognition.
AB  - Alloreactive T cells are core mediators of graft rejection and are a potent
      barrier to transplantation tolerance. It was previously unclear how T cells
      educated in the recipient thymus could recognize allogeneic HLA molecules.
      Recently it was shown that both naive and memory CD4+ and CD8+ T cells are
      frequently cross-reactive against allogeneic HLA molecules and that this
      allorecognition exhibits exquisite peptide and HLA specificity and is dependent
      on both public and private specificities of the T cell receptor. In this review
      we highlight new insights gained into the immunogenetics of allorecognition, with
      particular emphasis on how viral infection and vaccination may specifically
      activate allo-HLA reactive T cells. We also briefly discuss the potential for
      virus-specific T cell infusions to produce GvHD. The progress made in
      understanding the molecular basis of allograft rejection will hopefully be
      translated into improved allograft function and/or survival, and eventually
      tolerance induction.

PMID- 22146830
TI  - Renal cancer and pneumothorax risk in Birt-Hogg-Dube syndrome; an analysis of 115
      FLCN mutation carriers from 35 BHD families.
AB  - BACKGROUND: Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant condition
      caused by germline FLCN mutations, and characterised by fibrofolliculomas,
      pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and
      pneumothorax risk of BHD have not yet been fully clarified. The main focus of
      this study was to assess the risk of renal cancer, the histological subtypes of
      renal tumours and the pneumothorax risk in BHD. METHODS: In this study we present
      the clinical data of 115 FLCN mutation carriers from 35 BHD families. RESULTS:
      Among 14 FLCN mutation carriers who developed renal cancer 7 were <50 years at
      onset and/or had multifocal/bilateral tumours. Five symptomatic patients
      developed metastatic disease. Two early-stage cases were diagnosed by
      surveillance. The majority of tumours showed characteristics of both eosinophilic
      variants of clear cell and chromophobe carcinoma. The estimated penetrance for
      renal cancer and pneumothorax was 16% (95% minimal confidence interval: 6-26%)
      and 29% (95% minimal confidence interval: 9-49%) at 70 years of age,
      respectively. The most frequent diagnosis in families without identified FLCN
      mutations was familial multiple discoid fibromas. CONCLUSION: We confirmed a high
      yield of FLCN mutations in clinically defined BHD families, we found a
      substantially increased lifetime risk of renal cancer of 16% for FLCN mutation
      carriers. The tumours were metastatic in 5 out of 14 patients and tumour
      histology was not specific for BHD. We found a pneumothorax risk of 29%. We
      discuss the implications of our findings for diagnosis and management of BHD.

PMID- 22146832
TI  - Time-dependent quantum dynamical simulations of C2 condensation under extreme
      conditions.
AB  - We report theoretical studies of the initial phase of bulk C(2) condensation into
      carbon nano-structures by means of Born-Oppenheimer and time-dependent quantum
      mechanical Liouville-von Neumann molecular dynamics based on the density
      functional tight-binding (DFTB) framework for electrons. We observe that the time
      dependent quantum mechanical approach leads to faster formation of carbon
      nanostructures than analogous Born-Oppenheimer simulations. Our results suggest
      that the condensation of bulk carbon is nonadiabatic in nature, with the critical
      role of electronic stopping as in ion-irradiation of materials. Contrary to time
      dependent quantum mechanical simulations, Born-Oppenheimer dynamics incorrectly
      predict that the short carbon chains obtained from initial reactive collisions
      between C(2) quickly evaporate, leading to much lower probability of secondary
      collisions and condensation. We also discuss some deficiencies in Born
      Oppenheimer dynamics that lead to unphysical charge polarization and electron
      transfer.

PMID- 22146831
TI  - Segmental chromosomal alterations lead to a higher risk of relapse in infants
      with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a
      SIOPEN collaborative study).
AB  - BACKGROUND: In neuroblastoma (NB), the presence of segmental chromosome
      alterations (SCAs) is associated with a higher risk of relapse. METHODS: In order
      to analyse the role of SCAs in infants with localised unresectable/disseminated
      NB without MYCN amplification, we have performed an array CGH analysis of tumours
      from infants enrolled in the prospective European INES trials. RESULTS: Tumour
      samples from 218 out of 300 enroled patients could be analysed. Segmental
      chromosome alterations were observed in 11%, 20% and 59% of infants enroled in
      trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3
      (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose
      tumours harboured SCA, in the whole population and in trials INES99.1 and
      INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04
      and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was
      the strongest predictor of poorer progression-free survival. CONCLUSION: In
      infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies
      patients who will require upfront treatment even in the absence of other clinical
      indication for therapy, whereas in infants with localised unresectable NB, a
      genomic profile characterised by the absence of SCA identifies patients in whom
      treatment reduction might be possible. These findings will be implemented in a
      future international trial.

PMID- 22146833
TI  - Handheld device review of abdominal CT for the evaluation of acute appendicitis.
AB  - Advances in handheld computing now allow review of DICOM datasets from remote
      locations. As the diagnostic ability of this tool is unproven, we evaluated the
      ability to diagnose acute appendicitis on abdominal CT using a mobile DICOM
      viewer. This HIPAA compliant study was IRB-approved. Twenty-five abdominal CT
      studies from patients with RLQ pain were interpreted on a handheld device
      (iPhone) using a DICOM viewer (OsiriX mobile) by five radiologists. All patients
      had surgical confirmation of acute appendicitis or follow-up confirming no acute
      appendicitis. Studies were evaluated for the ability to find the appendix,
      maximum appendiceal diameter, presence of an appendicolith, periappendiceal
      stranding and fluid, abscess, and an assessment of the diagnosis of acute
      appendicitis. Results were compared to PACS workstation. Fifteen cases of acute
      appendicitis were correctly identified on 98% of interpretations, with no false
      positives. Eight appendicoliths were correctly identified on 88% of
      interpretations. Three abscesses were correctly identified by all readers.
      Handheld device measurement of appendiceal diameter had a mean 8.6% larger than
      PACS measurements (p = 0.035). Evaluation for acute appendicitis on abdominal CT
      studies using a portable device DICOM viewer can be performed with good
      concordance to reads performed on PACS workstations.

PMID- 22146834
TI  - Image analysis approach for development of a decision support system for
      detection of malaria parasites in thin blood smear images.
AB  - This paper describes development of a decision support system for diagnosis of
      malaria using color image analysis. A hematologist has to study around 100 to 300
      microscopic views of Giemsa-stained thin blood smear images to detect malaria
      parasites, evaluate the extent of infection and to identify the species of the
      parasite. The proposed algorithm picks up the suspicious regions and detects the
      parasites in images of all the views. The subimages representing all these
      parasites are put together to form a composite image which can be sent over a
      communication channel to obtain the opinion of a remote expert for accurate
      diagnosis and treatment. We demonstrate the use of the proposed technique for use
      as a decision support system by developing an android application which
      facilitates the communication with a remote expert for the final confirmation on
      the decision for treatment of malaria. Our algorithm detects around 96% of the
      parasites with a false positive rate of 20%. The Spearman correlation r was 0.88
      with a confidence interval of 0.838 to 0.923, p<0.0001.

PMID- 22146835
TI  - Inflammatory peeling skin syndrome caused a novel mutation in CDSN.
AB  - Generalized peeling skin syndrome (PSS) is a rare autosomal recessive dermatosis
      manifesting with continuous exfoliation of the stratum corneum. The inflammatory
      (type B) subtype of PSS was recently found to be caused by deleterious mutations
      in the CDSN gene encoding corneodesmosin, a major component of desmosomal
      junctions in the uppermost layers of the epidermis. In the present study, we
      assessed a 10-month-old baby, who presented with generalized superficial peeling
      of the skin. Using PCR amplification and direct sequencing, we identified the
      third PSS-associated mutation in CDSN, a homozygous 4 bp duplication in the
      second exon of the gene (c.164_167dup GCCT; p.Thr57ProfsX6). These data further
      support the notion that corneodesmosin deficiency impairs cell-cell adhesion in
      the upper epidermis, paving the way for an abnormal inflammatory response due to
      epidermal barrier disruption.

PMID- 22146836
TI  - Association of serum interleukin-18 and other biomarkers with disease severity in
      adults with atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic inflammatory disease of the skin for which
      there are no reliable biomarkers to assess clinical severity. Serum interleukin
      18 (IL-18) levels may be associated with AD severity. To identify putative
      biomarkers associated with clinical severity in adult AD patients, we enrolled
      121 adult AD patients (mean age 35.7 years) and 50 healthy controls (mean age
      31.7 years). We compared these groups for blood eosinophils and serum levels of
      IL-18, thymus and activation-regulated chemokine (TARC), total IgE, and lactate
      dehydrogenase (LDH). We also determined S. aureus enterotoxin B (SEB) specific
      IgE levels and the SCORingAD (SCORAD) scores for AD patients. For AD patients,
      stepwise logistic regression was used to estimate odds ratios (OR) for each
      biomarker for the likelihood of having AD, and multiple linear regression was
      used to identify biomarkers associated with SCORAD scores. Compared with healthy
      controls, adult AD patients had higher levels of IL-18, TARC, total IgE,
      eosinophils, and LDH. TARC levels had the highest OR for AD occurrence, while the
      OR for IL-18 was insignificant. Also, IL-18 was not related to the presence of
      SEB-IgE. Notably, IL-18 levels were significantly associated with SCORAD scores,
      as were TARC, total IgE, and LDH levels. A panel of biomarkers (IL-18, TARC,
      total IgE, and LDH) may be more useful to accurately assess clinical severity in
      adult AD patients.

PMID- 22146837
TI  - [Drafting expert opinion reports in medical liability processes].
AB  - In a medical liability process a medical expert takes on an outstanding position.
      He is the one process participant who preprograms the decision of the judge.
      However, he does not as such have an independent investigative competence and
      must understand his role as being an accessory to the judge. In view of this key
      role, the necessary expert competence and a basic legal knowledge, adequate
      preparation for the assignment and a meticulous study of the case file are
      indispensible. According to S 839 paragraph 1 of the German Civil Code
      (Burgerliches Gesetzbuch, BGB) an expert witness nominated by a court of law is
      liable to compensate damages if he writes an incorrect expert opinion either
      deliberately or due to gross negligence. The expert witness must also be
      objective and unprejudiced towards the parties involved or the accused/defendant.
      Civil processes and criminal proceedings both have legal peculiarities which the
      expert witness must bear in mind. The foundation of the function as an expert
      witness in a civil process is the order of the court to take evidence which the
      expert must adhere to. In this case the parties must be considered as being equal
      before the law. In contrast the procedure in criminal processes follows the
      principle of official investigation and the absolute principle of in dubio pro
      reo. From this it follows that the evidence of causality must be proven with a
      probability close to certainty. Advice for the construction of expert opinion
      statements can be found in this article.

PMID- 22146839
TI  - [Experienced anesthesiologists indispensable : anesthesia management of
      transcatheter aortic valve implantation].

PMID- 22146840
TI  - Quality of life in patients with inflammatory bowel disease: translation,
      validity, reliability and sensitivity to change of the Norwegian version of the
      short health scale (SHS).
AB  - PURPOSE: The aims of this study were to investigate the psychometric properties
      of the Norwegian version of the short health scale (SHS), and to study the impact
      of socio-demographic and clinical data. METHODS: A total of 140 patients without
      severe disease activity were included. The participants completed the SHS and
      three other well-validated HRQoL questionnaires short form 36, inflammatory bowel
      disease questionnaire and the rating form of inflammatory bowel disease patient
      concerns at the baseline. Sixty-three participants completed the SHS at a second
      visit after 6 months in order to calculate test-retest reliability and
      responsiveness. In addition, socio-demographic and clinical variables were
      obtained and entered into a linear regression analysis if they were found to be
      significantly associated with SHS outcome. RESULTS: Validity was confirmed by
      good correlation with other similar HRQoL constructs and the ability to
      discriminate between IBD symptom scores. The reliability was strong (Cronbach's
      alpha 0.85). The test-retest reliability in three out of four SHS items was weak,
      but the questionnaire demonstrated a good responsiveness. Current IBD symptoms
      were the most important predictor of SHS outcome. CONCLUSIONS: The Norwegian SHS
      demonstrated satisfactory psychometrical properties and is suitable for use in
      the follow-up of IBD patients.

PMID- 22146841
TI  - Validation of a quality-of-life scale for women with bladder pain
      syndrome/interstitial cystitis.
AB  - PURPOSE: To validate a disease-specific scale to measure the impact of symptoms
      of bladder pain syndrome/interstitial cystitis (BPS/IC), a condition that affects
      up to 6.5% of U.S. women. METHODS: Participants were drawn from the RAND
      Interstitial Cystitis Epidemiology (RICE) Study, a telephone probability survey
      of 146,231 US households. Women who met RICE BPS/IC symptom criteria (n = 3,397)
      completed the 6-item RAND Bladder Symptom Impact scale (RICE BSI-6). The RICE BSI
      6 was adapted from a scale used to assess the impact of diabetes on life and
      sexuality and modified based on expert input on face validity and focus group
      work; items specific to diabetic symptoms were eliminated. Validated scales of
      symptom severity, mental- and physical-health-related quality of life (QoL),
      depression, coping, and perceived control were used to assess convergent
      validity. RESULTS: The RICE BSI-6 (alpha = 0.92) was significantly related to
      greater symptom severity, worse general mental- and physical-health-related QoL,
      more severe depression symptoms, and lower perceived control over life in general
      and over BPS/IC symptoms (P values < .05). It was also associated with less use
      of distancing coping (P < .05). CONCLUSION: The RICE BSI-6 shows excellent
      internal consistency and strong convergent validity. It can be used to examine
      the effects of psychosocial and treatment interventions on QoL among women with
      BPS/IC.

PMID- 22146842
TI  - Synthesis, characterisation and magnetic study of a cyano-substituted dysprosium
      double decker single-molecule magnet.
AB  - Bis(octacyanophthalocyanine)dysprosium(III) (1) has been synthesised,
      characterised and magnetically studied. By the incorporation of cyano
      substituents on the phthalocyanine (Pc) rings, a starting point has been created
      for the chemical modification of double deckers for the purpose of surface self
      assembly. The modification of the rings leaves the magnetic properties of the
      double decker largely unaffected.

PMID- 22146843
TI  - Comment on Bock et al. Occlusion of surgical opening of the ventricular system
      with fibrinogen-coated collagen fleece: a case collection study. Acta Neurochir
      (2011) 153:533-539.

PMID- 22146845
TI  - Cement leakage as a possible complication of balloon kyphoplasty--is there a
      difference between osteoporotic compression fractures (AO type A1) and incomplete
      burst fractures (AO type A3.1)?
AB  - BACKGROUND: Besides the treatment of osteoporotic vertebral compression fractures
      of AO type A1, balloon kyphoplasty (BKP) is seen as a therapeutic option even in
      the treatment of incomplete osteoporotic burst fractures (AO type A3.1). However,
      due to involvement of the posterior vertebral body wall, the risk of cement
      leakages is considered to be higher. This study focuses on the frequency and
      pattern of cement leakages in AO type A3.1 fractures compared with osteoporotic
      compression fractures (AO type A1). PATIENTS AND METHODS: Retrospective cohort
      analysis was done of all patients (n = 138) treated by BKP for osteoporotic
      vertebral fractures (n = 173) between January 2007 and December 2010 in our
      department. Cement extravasations into three pre-defined anatomical compartments
      were evaluated on postoperative CT scans of the augmented vertebral bodies, with
      even minor cement detections beyond the vertebral body's wall being strictly
      inidicated as leakages. The frequency of cement leakages in relation to the
      fracture type was statistically analyzed using Pearson's chi-square test.
      Clinical and radiological follow-up was done 6 weeks, 3 and 6 months
      postoperatively. RESULTS: The overall cement leakage rate of BKP in 173 treated
      osteoporotic vertebral fractures was 30.6%. Cement extravasations were detected
      in 20.3% of A1.1, 30.5% of A1.2, 37.8% of A1.3, and 39.0% of A3.1 fractures,
      respectively. There was no statistically significant difference in the leakage
      rate between A3.1 and all A1 fractures (28.0%; p > 0.05), but between A3.1 and
      A1.1 fractures (p < 0.05). Intraspinal cement extravasations, being the most
      dangerous, were seen in 25.5% of all leakages (n = 53), whereas in relation to
      the total number of treated fracture types, there were only 5.1% intraspinal
      leakages in A1.1, 5.6% in A1.2, 10.9% in A1.3, and 9.8% in A3.1 fractures. Two of
      13 patients with intraspinal leakages and 1 patient with a paraaortal
      anterolateral cement extravasation needed surgical revisions. Two pulmonary PMMA
      cement embolisms were detected, but without any clinical consequences. None of
      the patients with cement leakages during BKP suffered from new neurological
      deficits. CONCLUSIONS: Cement leakages remain a problem in BKP. Although there
      was no significant difference between AO type A3.1 and all A1 fractures, subgroup
      analysis revealed a statistically significant higher risk of cement extrusions in
      A3.1 compared to A1.1 fractures. None of the affected patients showed new
      neurological deficits due to cement extravasations. Still, balloon kyphoplasty
      can be considered a safe procedure, even in the treatment of painful osteoporotic
      vertebral fractures of AO type A3.1.

PMID- 22146846
TI  - Salvage treatment of distant recurrent brain metastases with Gamma Knife surgery.
AB  - BACKGROUND: The aim of the study was to analyze the results following salvage
      Gamma Knife(r) surgery (GKS) for distant recurrent brain metastases in patients
      previously treated with GKS for brain metastases. METHODS: Survival time and
      freedom from new distant recurrences (DR) were studied in 251 patients treated
      with salvage GKS for brain metastases that had developed following a first GKS.
      The patients were followed prospectively and the results related to a number of
      patient parameters as well as the results following the first GKS. RESULTS: The
      median survival time was 9.6 months, and the median time of freedom from
      developing DR was 7.5 months after salvage GKS. The survival time was unrelated
      to age, gender, prior WBRT, and primary disease. It was significantly longer in
      patients with a single DR at salvage GKS as compared to those with multiple ones
      (16 versus 8.3 months). Patients with 2-4 DRs lived longer than those with >4
      lesions, 10 versus 5.8 months. The survival was significantly longer following
      salvage GKS as compared to following the first GKS. The prognosis of a patient
      with DR may therefore be less ominous than previously assumed. A classification
      system for DRs based on their clinical impact and treatability is therefore
      suggested. CONCLUSIONS: The longer survival time following salvage GKS as
      compared to following the first GKS suggests that many patients benefit from
      salvage GKS. A classification system of DR is suggested to estimate its clinical
      impact.

PMID- 22146847
TI  - Aquaporin-4 expression is not elevated in mild hydrocephalus.
AB  - BACKGROUND: Aquaporin-4 (aqp-4) is a member of water channel family proteins
      primarily expressed in the central nervous system. Physiologically it is the main
      channel providing water transport into the nervous system water compartments and
      across the blood-brain barrier. Several studies demonstrated its compensatory
      role in severe hydrocephalus. However, its role is not clear during the initial
      stages of hydrocephalus. OBJECTIVE: This study was designed to investigate aqp-4
      expression in less severe forms of hydrocephalus and to determine its role in
      disease progression. METHODS: Twenty-five male Wistar-Hannover rats, were
      distributed into experimental (n = 20) and control (n = 5) groups. Hydrocephalus
      was induced in the experimental group by injection of 5 MUl 25% kaolin suspension
      into the cisterna magna. Control animals received an injection of 5 MUl normal
      saline. Eight weeks later, the animals were killed by the perfusion-fixation
      method. Immunohistochemical and Western blot analysis were performed. RESULTS:
      Ventricular dilatations were noted in all experimental animals. Both groups
      demonstrated positive immunoreactive signals to aqp-4. Immunohistochemically
      there were no changes in aqp-4 pattern and expression intensity between
      experimental and control animals. Similarly, Western blot analysis revealed mean
      aqp-4 values in experimental and control groups as 0.3436 and 0.3917,
      respectively, and the difference did not reach statistical significance (p >
      0.05). CONCLUSION: Our results indicate that aqp-4 is not up-regulated during the
      initial stages of hydrocephalus. This implies that aqp-4 may not play a
      significant role in hydrocephalus compensation until severe ventricular
      dilatation occurs.

PMID- 22146848
TI  - Morphological and immunohistochemical characterization of sarcomatous tumors in
      wild-type and genetically engineered mice.
AB  - Malignant soft tissue tumors are commonly observed in wild-type and gene-targeted
      mice. These tumors have different degrees of differentiation, cellularity,
      cellular atypia, nuclear pleomorphism, normal and abnormal mitosis, and giant
      tumor cells with enlarged polylobulated nuclei. They are often diagnosed as
      pleomorphic sarcoma, undifferentiated sarcoma, fibrosarcoma, malignant fibrous
      histiocytoma, sarcoma, or sarcoma, not otherwise specified. Pleomorphic sarcomas
      have no morphological differentiation toward a differentiated mesenchymal or
      other tumor type in hematoxylin and eosin-stained sections. With the use of
      immunohistochemistry, human and mouse, tumors associated with these broad
      nonspecific diagnoses can often be demonstrated to be of a specific cellular
      lineage. With mouse models being used to delineate the molecular mechanisms,
      pathogenesis, and cellular origin of human sarcomas, it will be necessary to
      correlate the morphological and cellular lineage and the molecular profiles of
      the pleomorphic tumors associated with these mouse models. The results presented
      here show that with the use of immunohistochemistry, the cellular lineage of many
      mouse tumors with pleomorphic features can be determined.

PMID- 22146849
TI  - Pathology methods for the evaluation of embryonic and perinatal developmental
      defects and lethality in genetically engineered mice.
AB  - The normal embryonic development of organs and other tissues in mice and all
      species is preprogrammed by genes. Inactivation of a gene involved in any stage
      of normal embryonic development can have severe consequences leading to embryonic
      or postnatal developmental defects and lethality. Pathology methods are reviewed
      for evaluating normal and abnormal placenta and embryo, especially after E12.5.
      These methods include pathology protocols for necropsy and histopathology in
      addition to references that will provide additional knowledge for embryo
      assessment including histology atlases and advanced embryo imaging techniques.

PMID- 22146850
TI  - Establishing a laboratory animal model from a transgenic animal: RasH2 mice as a
      model for carcinogenicity studies in regulatory science.
AB  - Transgenic animal models have been used in small numbers in gene function studies
      in vivo for a period of time, but more recently, the use of a single transgenic
      animal model has been approved as a second species, 6-month alternative (to the
      routine 2-year, 2-animal model) used in short-term carcinogenicity studies for
      generating regulatory application data of new drugs. This article addresses many
      of the issues associated with the creation and use of one of these transgenic
      models, the rasH2 mouse, for regulatory science. The discussion includes
      strategies for mass producing mice with the same stable phenotype, including
      constructing the transgene, choosing a founder mouse, and controlling both the
      transgene and background genes; strategies for developing the model for
      regulatory science, including measurements of carcinogen susceptibility,
      stability of a large-scale production system, and monitoring for uniform
      carcinogenicity responses; and finally, efficient use of the transgenic animal
      model on study. Approximately 20% of mouse carcinogenicity studies for new drug
      applications in the United States currently use transgenic models, typically the
      rasH2 mouse. The rasH2 mouse could contribute to animal welfare by reducing the
      numbers of animals used as well as reducing the cost of carcinogenicity studies.
      A better understanding of the advantages and disadvantages of the transgenic
      rasH2 mouse will result in greater and more efficient use of this animal model in
      the future.

PMID- 22146852
TI  - A novel thermostable and glucose-tolerant beta-glucosidase from Fervidobacterium
      islandicum.
AB  - An open reading frame (ORF) encoding the enzyme beta-glucosidase from the
      extremely thermophilic bacterium Fervidobacterium islandicum has been identified,
      cloned and sequenced. The bgl1A gene was cloned in a pET-Blue1 vector and
      transformed in Escherichia coli, resulting in high-level expression of beta
      glucosidase FiBgl1A that was purified to homogeneity in a two-step purification.
      FiBgl1A is composed of 459 amino acid residues and showed high homology to
      glycoside hydrolase family 1 proteins. It exhibited highest activity towards p
      nitrophenyl-beta-D: -glucopyranoside with an optimum activity at pH 6.0 and 7.0
      and at 90  degrees C. The enzyme is resistant to glucose inhibition. Furthermore,
      it did not require divalent cations for activity, nor was it affected by the
      addition of p-chloromercuribenzoate (10 mM), EDTA (10 mM), urea (10 mM) or
      dithiothreitol (10 mM). Addition of surfactants (with the exception of SDS) and a
      number of solvents enhanced the activity of FiBgl1A. It also displayed remarkable
      activity across a broad temperature range (80-100  degrees C). The thermoactivity
      and thermostability of FiBgl1A and its resistance to denaturing and reducing
      agents make this enzyme a potential candidate for industrial applications.

PMID- 22146854
TI  - Metal-free, organocatalytic cascade formation of C-N and C-O bonds through dual
      sp3 C-H activation: oxidative synthesis of oxazole derivatives.
AB  - An organocatalytic cascade reaction that involves the formation of C-N, C-O and
      C=N bonds in one process via dual sp(3) C-H activation has been developed. This
      protocol affords a facile metal-free methodology for the synthesis of oxazole
      derivatives in air under mild conditions.

PMID- 22146851
TI  - 3-dimensional imaging modalities for phenotyping genetically engineered mice.
AB  - A variety of 3-dimensional (3D) digital imaging modalities are available for
      whole-body assessment of genetically engineered mice: magnetic resonance
      microscopy (MRM), X-ray microcomputed tomography (microCT), optical projection
      tomography (OPT), episcopic and cryoimaging, and ultrasound biomicroscopy (UBM).
      Embryo and adult mouse phenotyping can be accomplished at microscopy or near
      microscopy spatial resolutions using these modalities. MRM and microCT are
      particularly well-suited for evaluating structural information at the organ
      level, whereas episcopic and OPT imaging provide structural and functional
      information from molecular fluorescence imaging at the cellular level. UBM can be
      used to monitor embryonic development longitudinally in utero. Specimens are not
      significantly altered during preparation, and structures can be viewed in their
      native orientations. Technologies for rapid automated data acquisition and high
      throughput phenotyping have been developed and continually improve as this
      exciting field evolves.

PMID- 22146853
TI  - Transient global cerebral ischemia induces up-regulation of MLTKalpha in
      hippocampal CA1 neurons.
AB  - MLTK (mixed-lineage kinase-like mitogen-activated protein triple kinase) is a
      member of the mitogen-activated protein kinase family and functioned as a mitogen
      activated kinase kinase kinase. MLTKalpha, one of the alternatively spliced forms
      of MLTK, could activate the c-Jun N-terminal kinase pathway, which involved in
      cellular stress responses and apoptosis. But the role of MLTKalpha in neural
      apoptosis was still unclear. Here, we performed a transient global cerebral
      ischemia model (TGCI) in adult rats and detected the dynamic changes of MLTKalpha
      in hippocampal CA1 neurons and brain cortex. We found the MLTKalpha expression
      was increased shortly after TGCI and peaked after 8 h. In spatial distribution,
      MLTKalpha was widely located in neurons rather than astrocytes and microglia.
      Moreover, there was a concomitant up-regulation of active caspase-3. Taken
      together, we hypothesized the up-regulation of MLTKalpha played an essential role
      in the apoptosis of hippocampal CA1 neurons.

PMID- 22146855
TI  - A theoretical evaluation of possible transition metal electro-catalysts for N2
      reduction.
AB  - Theoretical studies of the possibility of forming ammonia electrochemically at
      ambient temperature and pressure are presented. Density functional theory
      calculations were used in combination with the computational standard hydrogen
      electrode to calculate the free energy profile for the reduction of N(2)
      admolecules and N adatoms on several close-packed and stepped transition metal
      surfaces in contact with an acidic electrolyte. Trends in the catalytic activity
      were calculated for a range of transition metal surfaces and applied potentials
      under the assumption that the activation energy barrier scales with the free
      energy difference in each elementary step. The most active surfaces, on top of
      the volcano diagrams, are Mo, Fe, Rh, and Ru, but hydrogen gas formation will be
      a competing reaction reducing the faradaic efficiency for ammonia production.
      Since the early transition metal surfaces such as Sc, Y, Ti, and Zr bind N
      adatoms more strongly than H-adatoms, a significant production of ammonia
      compared with hydrogen gas can be expected on those metal electrodes when a bias
      of -1 V to -1.5 V vs. SHE is applied. Defect-free surfaces of the early
      transition metals are catalytically more active than their stepped counterparts.

PMID- 22146858
TI  - Classes and consequences of multiple maltreatment: a person-centered analysis.
AB  - While the overwhelming majority of research on the consequences of childhood
      maltreatment reports differential outcomes of specific maltreatment subtypes
      (e.g., physical abuse vs. emotional abuse) as though they are independent,
      maltreatment experiences often occur in combination. The present study evaluated
      multiple maltreatment experiences in a sample of 2,637 undergraduate students who
      reported on childhood maltreatment and current adjustment. The authors used
      latent class analysis to examine predominant patterns of multiple maltreatment
      experiences and investigated indices of psychosocial adjustment associated with
      those patterns. Results suggested that specific constellations of multiple
      maltreatment have qualitatively different associations with adjustment. Emotional
      abuse, alone or in combination with other maltreatment types, was especially
      salient for psychopathology (e.g., anxiety, depression), while a combination of
      physical and emotional abuse was most strongly associated with conduct-related
      problems (e.g., substance use, risky sexual behavior). These findings have both
      practical and empirical significance for understanding and classifying
      experiences of maltreatment.

PMID- 22146856
TI  - Molecular techniques in ecohealth research toolkit: facilitating estimation of
      aggregate gastroenteritis burden in an irrigated periurban landscape.
AB  - Assessment of microbial hazards associated with certain environmental matrices,
      livelihood strategies, and food handling practices are constrained by time
      consuming conventional microbiological techniques that lead to health risk
      assessments of narrow geographic or time scope, often targeting very few
      pathogens. Health risk assessment based on one or few indicator organisms
      underestimates true disease burden due a number of coexisting causative
      pathogens. Here, we employed molecular techniques in a survey of Cryptosporidium
      parvum, Giardia lamblia, Campylobacter jejuni, Escherichia coli O157:H7, Listeria
      monocytogenes, Salmonella spp., Shigella spp., Vibrio cholera, and Rotavirus A
      densities in canal water with respect to seasonality and spatial distribution of
      point-nonpoint pollution sources. Three irrigational canals stretching across
      nearly a 150-km(2) periurban landscape, traditionally used for agricultural
      irrigation but function as vital part of municipal wastewater stabilization in
      recent years, were investigated. Compiled stochastic data (pathogen
      concentration, susceptible populations) and literature-obtained deterministic
      data (pathogen dose-response model parameter values) were used in estimating
      waterborne gastroenteritis burden. Exposure scenarios include swimming or
      fishing, consuming canal water-irrigated vegetables, and ingesting or inhaling
      water aerosols while working in canal water-irrigated fields. Estimated annual
      gastroenteritis burden due individual pathogens among the sampling points was 
      10.6log(10) to -2.2log(10) DALYs. Aggregated annual gastroenteritis burden due
      all the target pathogens per sampling point was -3.1log(10) to -1.9log(10) DALYs,
      far exceeding WHO acceptable limit of -6.0log(10) DALYs. The present approach
      will facilitate the comprehensive collection of surface water microbiological
      baseline data and setting of benchmarks for interventions aimed at reducing
      microbial hazards in similar landscapes worldwide.

PMID- 22146859
TI  - Effects of placement type on the language developmental trajectories of
      maltreated children from infancy to early childhood.
AB  - This study describes the developmental trajectories of language skills in infants
      with substantiated maltreatment histories over a 5-year period and evaluates the
      effect of three different custodial placements on their language trajectories
      over time: in-home (remaining in the care of the biological parent/parents),
      nonkin foster care, and nonparental kinship care. Participants included 963
      infants reported to child protective services prior to their first birthday and
      whose maltreatment was substantiated. Results from covariate-controlled growth
      modeling revealed no significant placement effects. Across all groups, children's
      auditory and expressive communication scores decreased significantly from Wave 1
      (intake) in the infants' first year to Wave 4, when children were about 3.5 years
      of age, then improved to baseline levels by Wave 5, when children were about 6
      years old. Despite these fluctuations, children's average language scores in each
      placement group remained below the population mean at each wave of the study.

PMID- 22146860
TI  - Initial implementation indicators from a statewide rollout of SafeCare within a
      child welfare system.
AB  - There is a strong movement toward implementation of evidence-based practices
      (EBP) in child welfare systems. The SafeCare parenting model is one of few parent
      training models that addresses child neglect, the most common form of
      maltreatment. Here, the authors describe initial findings from a statewide effort
      to implement the EBP, SafeCare(r), into a state child welfare system. A total of
      50 agencies participated in training, with 295 individuals entering training to
      implement SafeCare. Analyses were conducted to describe the trainee sample,
      describe initial training and implementation indicators, and to examine
      correlates of initial training performance and implementation indicators. The
      quality of SafeCare uptake during training and implementation was high with
      trainees performing very well on training quizzes and role-plays, and
      demonstrating high fidelity when implementing SafeCare in the field (performing
      over 90% of expected behaviors). However, the quantity of implementation was
      generally low, with relatively few providers (only about 25%) implementing the
      model following workshop training. There were no significant predictors of
      training or implementation performance, once corrections for multiple comparisons
      were applied. The Discussion focuses on challenges to large-scale system-wide
      implementation of EBP.

PMID- 22146861
TI  - Mixed methods for implementation research: application to evidence-based practice
      implementation and staff turnover in community-based organizations providing
      child welfare services.
AB  - Many public sector service systems and provider organizations are in some phase
      of learning about or implementing evidence-based interventions. Child welfare
      service systems represent a context where implementation spans system,
      management, and organizational concerns. Research utilizing mixed methods that
      combine qualitative and quantitative design, data collection, and analytic
      approaches are particularly well suited to understanding both the process and
      outcomes of dissemination and implementation efforts in child welfare systems.
      This article describes the process of using mixed methods in implementation
      research and provides an applied example of an examination of factors impacting
      staff retention during an evidence-based intervention implementation in a
      statewide child welfare system. The authors integrate qualitative data with
      previously published quantitative analyses of job autonomy and staff turnover
      during this statewide implementation project in order to illustrate the utility
      of mixed method approaches in providing a more comprehensive understanding of
      opportunities and challenges in implementation research.

PMID- 22146862
TI  - Extracapsular dissection for minimal resection of benign parapharyngeal tumor.
AB  - Extracapsular dissection (ECD) is thought to be effective in treating benign
      tumors and minimally invasive. Nonetheless, its application and feasibility in
      treating benign parapharyngeal space (PPS) tumor, the neoplasm located in the
      complex anatomical space, have never been investigated. The aim of this study is
      to evaluate the utility and efficacy of transcervical ECD in treating benign PPS
      tumors. From 1996 to 2009, 54 patients with PPS tumors were treated by the
      designated surgeon. Excluding nine patients who were initially regarded as the
      potential candidates for ECD treatment but failed to meet the inclusion criteria,
      22 patients who received the procedure were retrospectively analyzed. In 22
      enrolled patients, 10 had pleomorphic adenoma while 6 had neurilemmoma. There
      were 13 PPS tumors located in the prestyloid space and 9 in the poststyloid
      space. The median volume of PPS tumors was 22.6 cm(3), and the median distance
      from tumor to skull base was 2.3 cm. The median length of incision was 4.5 cm
      with the ECD intervention. No major intra- or post-operative complications were
      noted and post-operative courses were unremarkable in long-term follow-up. This
      study demonstrates that ECD is an effective and safe treatment for selected
      benign PPS tumors. It has a favorable clinical outcome and an acceptable
      aesthetic result, and can be performed in a minimally invasive fashion.
      Therefore, it is suggested that ECD be included in the treatment modalities of
      benign PPS tumors.

PMID- 22146863
TI  - An essential dose of cisplatin for super-selective intra-arterial infusion
      concomitant with radiotherapy in patient with maxillary squamous cell carcinoma.
AB  - The present study investigated the efficacy and safety of using a lower dose of
      cisplatin (CDDP) in super-selective intra-arterial concurrent chemoradiotherapy
      (SSIACRT) to treat maxillary squamous cell carcinoma. 10 patients with maxillary
      squamous cell carcinoma (T3 n = 6, T4a n = 4) without regional or distant
      metastasis were treated by SSIACRT. The CDDP dose per course was 100 mg/body,
      i.e. 50-80 mg/m(2). 6-9 weeks after SSIACRT, partial maxillectomy was performed
      on all patients. Clinical and histological responses, survival rates, and adverse
      events were investigated. 10 (100%) of 10 patients achieved both clinical and
      pathological complete or partial remission. The 3-year overall and disease-free
      survival rates were 100 and 90%, respectively. Grade 3 toxicity was experienced
      by two patients. In conclusion, the SSIACRT regimen with a lower dose of CDDP
      (100 mg/body) had an equivalent therapeutic outcome and lower toxic outcome
      compared to a higher dose of CDDP. This regimen could be an effective and safe
      therapeutic modality for maxillary squamous cell carcinoma except T4b and N1/2
      disease.

PMID- 22146865
TI  - Island cartilage tympanoplasty in revision cases: anatomic and functional
      results.
AB  - We report our experience with island cartilage tympanoplasty in revision cases
      and assess the anatomical and functional outcomes. We conducted a retrospective
      chart review at a tertiary referral center for patients who underwent revision
      tympanoplasty using cartilage with the island technique without mastoidectomy
      between January 2002 and December 2008. 60 cases were included in the study and
      successful closure without reperforation was obtained in 52 of 60 patients (87%).
      Three failed cases underwent a subsequent procedure endaurally with a positive
      result (92% accumulated success rate). Average postoperative pure-tone audiometry
      air-bone gap was 13 +/- 7 dB compared with 21 +/- 11 dB preoperatively (p =
      0.004). An overall postoperative air-bone gap of 20 dB or less was achieved in 46
      of the 60 patients (76.7%). Tympanoplasty with island cartilage grafting is a
      reliable procedure for revision cases with excellent anatomic results as well as
      significant improvement of hearing.

PMID- 22146864
TI  - The nucleotide polymorphisms within the Epstein-Barr virus C and Q promoters from
      nasopharyngeal carcinoma affect transcriptional activity in vitro.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human gamma herpesvirus that is
      associated with Burkitt's lymphoma (BL), gastric carcinoma, nasopharyngeal
      carcinoma (NPC), and NK/T-cell lymphoma. Two viral promoters, Cp and Qp, are
      important for EBV latent infection. The latency Cp, which is used in primary
      infection, drives expression of the full spectrum of EBV nuclear antigens. Qp is
      active in EBV-associated tumors and drives the latency I/II expression pattern.
      In this study, we determined nucleotides polymorphisms in the Cp and Qp promoter
      regions in peripheral blood mononuclear cells (PBMCs) from Cantonese healthy
      carriers and in biopsies of NPC, nasal NK/T lymphoma, BL, and gastric carcinoma.
      The sequence changes of -12G>T and +69 C>T in Cp and -197 G>A and +1 G>C in Qp
      were frequently identified in NPC. Transient transfection studies using
      luciferase gene reporters revealed a significant reduction (57.11%) in gene
      expression from the Cp +69T variant and increased expression (43.5%) from the Qp
      +1C variant compared to the prototype, suggesting that these sequence variations
      affect promoter activity. Our results indicate that the nucleotides polymorphisms
      in Cp and Qp occur frequently in NPC and might contribute to the oncogenesis of
      EBV.

PMID- 22146866
TI  - Prediction and Cross-Situational Consistency of Daily Behavior across Cultures:
      Testing Trait and Cultural Psychology Perspectives.
AB  - Trait and cultural psychology perspectives on the cross-situational consistency
      of behavior, and the predictive validity of traits, were tested in a daily
      process study in the United States (N = 68), an individualistic culture, and the
      Philippines (N = 80), a collectivistic culture. Participants completed the
      Revised NEO Personality Inventory (Costa & McCrae, 1992) and a measure of self
      monitoring, then reported their daily behaviors and associated situational
      contexts for approximately 30 days. Consistent with trait perspectives, the Big
      Five traits predicted daily behaviors in both cultures, and relative
      (interindividual) consistency was observed across many, although not all,
      situational contexts. The frequency of various Big Five behaviors varied across
      relevant situational contexts in both cultures and, consistent with cultural
      psychology perspectives, there was a tendency for Filipinos to exhibit greater
      situational variability than Americans. Self-monitoring showed some ability to
      account for individual differences in situational variability in the American
      sample, but not the Filipino sample.

PMID- 22146867
TI  - Overexpression of the wild potato eIF4E-1 variant Eva1 elicits Potato virus Y
      resistance in plants silenced for native eIF4E-1.
AB  - Potato virus Y (PVY) is the most important viral pathogen of cultivated potato
      (Solanum tuberosum) from a commercial perspective, causing severe losses in both
      tuber quality and yield worldwide. Specific accessions of wild potato species
      exhibit resistance against PVY but efforts to transfer the trait to cultivated
      material have not yielded widely adopted varieties. Because amino acid
      substitutions at specific domains of host factor eIF4E-1 often confer resistance
      to various crops, we sequenced the associated genes expressed in wild potato
      plants. A novel eIF4E-1 variant, designated here as Eva1, was identified in S.
      chacoense, S. demissum, and S. etuberosum. The protein contains amino acid
      substitutions at ten different positions when compared to its cultivated potato
      (S. tuberosum) homolog. In the yeast two-hybrid system, Eva1 failed to bind VPg,
      a viral protein required for infectivity. Overexpression of the associated cDNA
      conferred PVY resistance to transgenic potato plants silenced for the native
      eIF4E-1 gene. Because the gene sources of Eva1 are sexually compatible with
      potato, the molecular strategies described can be employed to develop
      'intragenic' potato cultivars.

PMID- 22146868
TI  - Modulating protein activity and cellular function by methionine residue
      oxidation.
AB  - The sulfur-containing amino acid residue methionine (Met) in a peptide/protein is
      readily oxidized to methionine sulfoxide [Met(O)] by reactive oxygen species both
      in vitro and in vivo. Methionine residue oxidation by oxidants is found in an
      accumulating number of important proteins. Met sulfoxidation activates
      calcium/calmodulin-dependent protein kinase II and the large conductance calcium
      activated potassium channels, delays inactivation of the Shaker potassium channel
      ShC/B and L-type voltage-dependent calcium channels. Sulfoxidation at critical
      Met residues inhibits fibrillation of atherosclerosis-related apolipoproteins and
      multiple neurodegenerative disease-related proteins, such as amyloid beta, alpha
      synuclein, prion, and others. Methionine residue oxidation is also correlated
      with marked changes in cellular activities. Controlled key methionine residue
      oxidation may be used as an oxi-genetics tool to dissect specific protein
      function in situ.

PMID- 22146869
TI  - Whole-body MRI in neurofibromatosis: incidental findings and prevalence of
      scoliosis.
AB  - OBJECTIVE: To demonstrate incidental findings and scoliosis on whole-body MRI
      (WBMRI) in patients with neurofibromatosis type 1 and 2 (NF1 & NF2,
      respectively), and schwannomatosis. MATERIALS AND METHODS: Institutional review
      board approval and written informed consent were obtained for this prospective
      HIPAA-compliant study. A total of 247 subjects (141 with NF1, 55 with NF2, 51
      with schwannomatosis; 132 women (53.5%); mean age, 41 years, range, 18-97 years)
      underwent WBMRI using coronal STIR (TR/TE: 4190/111 ms, TI: 150 ms) and T1
      weighted images (TR/TE: 454/10 ms), 10-mm slice thickness, imaging time ~40 min.
      Images were reviewed for the presence of incidental findings, outside of nerve
      sheath tumors. The presence of scoliosis was recorded and curve morphology was
      assessed and quantified. RESULTS: Incidental findings other than scoliosis were
      recorded in 104/247 (42%) patients, most often affecting the musculoskeletal
      system (65/247 patients, 26%). We found 16/247 (6.5%) significant incidental
      findings likely to affect clinical management, including avascular necrosis of
      bone in eight patients (five with NF2), eight insufficiency fractures, and four
      non-neurogenic neoplasms (Hodgkin's lymphoma, liposarcoma, dermoid cyst, large
      uterine myoma requiring excision). Scoliosis was seen in 50/247 patients (20%),
      including 8/55 with NF2 (15%) and 11/51 with schwannomatosis (22%). CONCLUSIONS:
      Incidental findings in the neurofibromatoses frequently involve the skeleton.
      Given the relatively high incidence of unsuspected osteonecrosis and stress
      fractures, close attention to the skeleton on WBMRI is advised. In addition,
      knowledge of common incidental findings can help clinicians prepare patients who
      undergo WBMRI for potential unexpected findings.

PMID- 22146870
TI  - Cell self-patterning on uniform PDMS-surfaces with controlled mechanical cues.
AB  - The exploitation of cell-instructive scaffolds with uniform physical/chemical
      surfaces and controlled stiffness will be greatly useful in tissue engineering
      applications to resemble the extracellular matrix (ECM) or topographical
      appearance of native tissues. We herein describe a versatile and straightforward
      method to assemble a polydimethylsiloxane (PDMS)-composite structure in which a
      uniformly laminin-coated membrane is placed on top of a micropatterned substrate
      that applies a stiffness gradient. This 'double-sheet' structure provides soft or
      stiff microdomains that guide the self-patterning of different cell types [e.g.
      chronic myeloid leukemia (KU812), cervix carcinoma (HeLa), NIH 3T3 and BJ],
      thereby stimulating their cytoskeletal remodeling. More interestingly, we used
      these uniform PDMS surfaces with patterned rigidity for obtaining co-cultures of
      tumor blood cells (KU812) and adherent fibroblasts (NIH 3T3) with spatially
      controlled distribution. Thus, beyond single-cell stiffening and mechanosensing,
      these surfaces should also be used as simple and feasible co-culture systems for
      mimicking and dissecting the bidirectional interactions between blood cells and
      specific stromal elements of their in vivo microenvironment.

PMID- 22146871
TI  - [Importance of lymph node dissection. Worthy of many questions].

PMID- 22146873
TI  - Time interval of increased risk for Clostridium difficile infection after
      exposure to antibiotics.
AB  - BACKGROUND: Clostridium difficile infections (CDIs) are common in developed
      countries and affect >250,000 hospitalized patients annually in the USA. The most
      important risk factor for the disease is antibiotic therapy. METHODS: To
      determine the period at risk for CDI after cessation of antibiotics, we performed
      a multicentre case-control study in the Netherlands between March 2006 and May
      2009. Three hundred and thirty-seven hospitalized patients with diarrhoea and a
      positive toxin test were compared with 337 patients without diarrhoea.
      Additionally, a control group of patients with diarrhoea due to a cause other
      than CDI (n=227) was included. RESULTS: In the month prior to the date of
      inclusion, CDI patients more frequently used an antibiotic compared with non
      diarrhoeal patients (77% versus 49%). During antibiotic therapy and in the first
      month after cessation of the therapy, patients had a 7-10-fold increased risk for
      CDI (OR 6.7-10.4). This risk declined in the period between 1 and 3 months after
      the antibiotic was stopped (OR 2.7). Similar results were observed when the
      second control group was used. All antibiotic classes, except first-generation
      cephalosporins and macrolides, were associated with CDI. Second- and third
      generation cephalosporins (OR 3.3 and 5.3, respectively) and carbapenems (OR 4.7)
      were the strongest risk factors for CDI. Patients with CDI used more antibiotic
      classes and more defined daily doses, compared with non-diarrhoeal patients.
      CONCLUSIONS: Antibiotic use increases the risk for CDI during therapy and in the
      period of 3 months after cessation of antibiotic therapy. The highest risk for
      CDI was found during and in the first month after antibiotic use. Our study will
      aid clinicians to identify high-risk patients.

PMID- 22146874
TI  - Comment on: Nucleotide sequence of the chromosomal region conferring multidrug
      resistance (R-type ASSuT) in Salmonella Typhimurium and monophasic Salmonella
      Typhimurium strains.

PMID- 22146876
TI  - Association between IL28B gene polymorphisms and sustained virological response
      in patients coinfected with HCV and HIV in Brazil.

PMID- 22146875
TI  - Growth phase-dependent expression of RND efflux pump- and outer membrane porin
      encoding genes in Acinetobacter baumannii ATCC 19606.
AB  - OBJECTIVES: To analyse the expression of resistance-nodulation-division (RND)
      efflux pumps and outer membrane porins during various growth phases of
      Acinetobacter baumannii ATCC 19606. METHODS: Expression of five different RND
      pump-encoding genes (adeB, adeG, adeJ, AciBau_2436 and AciBau_2746) and two outer
      membrane porin-encoding genes (carO and oprD) was analysed at four growth
      timepoints, representing early, mid and late log phases and the stationary phase
      using quantitative RT-PCR. RESULTS: The adeB and adeJ RND pump genes were
      expressed at higher levels than all of the other RND pumps, though their
      expression was reduced at higher cell density. The adeG gene was found to be
      constitutively expressed, albeit at much lower levels than those seen for adeB or
      adeJ. The previously uncharacterized AciBau_2436 was found to be expressed in the
      early exponential phase. The expression level of oprD was found to be inversely
      proportional to cell density, while that of carO was found to increase in the mid
      log phase but then decrease in the later stages of the growth phase. CONCLUSIONS:
      This work shows cell density-dependent expression of adeB, adeJ, AciBau_2436,
      carO and oprD genes, suggesting a role of global regulatory mechanisms in the
      expression of these genes in A. baumannii ATCC 19606.

PMID- 22146877
TI  - Report of a Salmonella enterica serovar Typhi isolate from India producing CMY-2
      AmpC beta-lactamase.

PMID- 22146878
TI  - A USA300 variant and other human-related methicillin-resistant Staphylococcus
      aureus strains infecting cats and dogs in France.
AB  - OBJECTIVES: To characterize methicillin-resistant Staphylococcus aureus (MRSA)
      clinical strains from cats and dogs in France, and to compare the clones
      identified with the distribution of French human MRSA. METHODS: Susceptibilities
      to antimicrobials were assessed by disc diffusion. Resistance and virulence genes
      were screened using a microarray-based assay. Isolates were additionally
      characterized by SmaI macrorestriction analysis and spa typing. RESULTS: From
      2006 to 2010, the proportion of MRSA infections in pets in France was low (1.8%),
      but most isolates (87.0%, 20/23) belonged to human clones. The most common clones
      were the Lyon clone (69.6%, 16/23), the livestock-associated CC398 (13.0%, 3/23)
      and the Geraldine clone (8.7%, 2/23). Interestingly, we report the first USA300
      clone infecting a European dog, which was probably imported by a US patient.
      CONCLUSIONS: Over a 5 year period, the proportion of MRSA infections in pets
      appears low (<2%) in France, but the distribution of the clones mostly mirrors
      the epidemiology of human invasive clones. These data highlight the role of pets
      as both victims and reservoirs of endemic, epidemic and/or invasive MRSA.

PMID- 22146879
TI  - Fish and Chips: a microfluidic perfusion platform for monitoring zebrafish
      development.
AB  - We have developed a multi-channel microfluidic perfusion platform for culturing
      zebrafish embryos and capturing live images of various tissues and organs inside
      the embryo. The Fish and Chips was micro-fabricated in silicon and glass for
      reproducibility and accuracy of the microfluidic structure. The microfluidic
      platform consists of three parts: a microfluidic gradient generator, a row of
      eight fish tanks, in which the fish embryos are individually placed, and eight
      output channels. The fluidic gradient generator supports dose-dependent drug and
      chemical studies. A unique perfusion system ensures a uniform and constant flow
      of media to the fish tank while the wastes are efficiently removed. The fish
      tanks restrict the embryo movements, except rotationally, for live imaging of
      internal tissues and organs. The embryos showed developmental abnormalities under
      the influence of the drug valproic acid (VPA).

PMID- 22146880
TI  - Sutureless amniotic membrane transplantation combined with narrow-strip
      conjunctival autograft for pterygium.
AB  - To study the efficacy and safety of sutureless amniotic membrane transplantation
      combined with narrow-strip conjunctival autograft and to investigate the clinical
      outcomes. Thirty eyes of 30 patients with primary pterygia were treated in this
      institutional study with excision followed by sutureless amniotic membrane
      transplantation combined with narrow-strip conjunctival autograft using fibrin
      glue tissue adhesive. The main outcome measures were the operating time for
      ocular surface reconstruction, the size of the pterygium and of the conjunctival
      autograft, postoperative complications, subjective complaints, and recurrences.
      The mean pterygium size was 3.12 +/- 0.92 mm and the mean operating time was 4.58
      +/- 1.10 min. Twenty-nine patients (96.7%) had no complaints after first
      postoperative week. Twenty-eight (93.3%) patients had no recurrences after 1 year
      follow-up. The sutureless amniotic membrane transplantation combined with narrow
      strip conjunctival autograft is an effective procedure with low rate of
      recurrence. This technique can be considered as a preferred grafting procedure
      for primary pterygium but further randomized controlled studies including larger
      populations are needed.

PMID- 22146881
TI  - Sentinel node biopsy in early gastric cancer: constant exertion for clinical
      application.

PMID- 22146882
TI  - Oncology health information quality on the Internet: a multilingual evaluation.
AB  - BACKGROUND: Oncologic Internet information quality is considered variable, but no
      comprehensive analysis exists to support this. We compared the quality of common
      malignancy Web sites to assess them for language or disease differences and to
      perform a quality comparison between medical and layperson terminology. METHODS:
      World Health Organization Health on the Net (HON) principles may be applied to
      Web sites by using an automated toolbar function. We used the Google search
      engine ( http://www.google.com ) to assess 10,200 Web sites using the keywords
      "Breast," "Colorectal," "Stomach," "Liver," "Pancreas," "Bile Duct," "Melanoma,"
      and "Thyroid," plus "cancer," in English, French, German, and Spanish. The
      searches were then repeated with alternative terms, such as "Bowel" and "Skin
      cancer." RESULTS: Less than a quarter of Web sites are HON accredited, with
      significant differences by malignancy type (P < 0.0001), language (P < 0.0001),
      and tertiles of the first 150 Web sites returned (P < 0.0001). French-language
      queries resulted in the most accredited Web sites returned. The use of
      alternative terms resulted in marked differences in accredited Web sites for
      hepatobiliary cancers. CONCLUSIONS: A lack of validation of most oncologic sites
      is present, with discrepancies in the quality and number of Web sites across
      diseases and languages, as well as medical and alternative terms. Physicians
      should encourage and participate in the development of informative, ethical, and
      reliable health Web sites on the Internet and direct patients to them.

PMID- 22146883
TI  - SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular
      carcinoma and its expression predicts poor prognosis.
AB  - BACKGROUND: SIRT1 is a NAD+-dependent deacetylase that plays crucial roles in
      many biological processes, including stress response, apoptosis, cellular
      metabolism, adaptation to calorie restriction, aging, and tumorigenesis. The
      purpose of this study is to elucidate the clinicopathological and functional
      significance of SIRT1 expression in hepatocellular carcinoma (HCC). METHODS:
      SIRT1 expression in HCC was determined by immunohistochemical staining. The
      results were correlated with clinicopathological parameters. SIRT1 was
      overexpressed in HCC cell line SK-Hep1 to study its role in tumorigenesis and
      resistance to chemotherapy. RESULTS: SIRT1 was overexpressed in 95 of 172 HCCs
      (55%). SIRT1 overexpression was associated with higher alpha-fetoprotein level,
      higher tumor grade, and absence of beta-catenin mutation. SIRT1 expression
      predicted poor long-term survival for patients with resected HCC. The elevated
      SIRT1 protein level in HCC was not attributable to the elevation of mRNA level.
      The half-life of SIRT1 protein was longer in cell lines with higher expression of
      SIRT1. We further demonstrated that SIRT1 was degraded by the 26S proteasome in
      an ubiquitin-dependent manner. Overexpression of SIRT1 promoted tumorigenesis and
      resistance to chemotherapeutical agent and sorafenib. CONCLUSIONS: SIRT1 is an
      oncogenic protein for HCC and is a predictor of worse outcome after surgical
      resection of HCC.

PMID- 22146884
TI  - Automatic estimation of pressure-dependent rate coefficients.
AB  - A general framework is presented for accurately and efficiently estimating the
      phenomenological pressure-dependent rate coefficients for reaction networks of
      arbitrary size and complexity using only high-pressure-limit information. Two
      aspects of this framework are discussed in detail. First, two methods of
      estimating the density of states of the species in the network are presented,
      including a new method based on characteristic functional group frequencies.
      Second, three methods of simplifying the full master equation model of the
      network to a single set of phenomenological rates are discussed, including a new
      method based on the reservoir state and pseudo-steady state approximations. Both
      sets of methods are evaluated in the context of the chemically-activated reaction
      of acetyl with oxygen. All three simplifications of the master equation are
      usually accurate, but each fails in certain situations, which are discussed. The
      new methods usually provide good accuracy at a computational cost appropriate for
      automated reaction mechanism generation.

PMID- 22146885
TI  - Intentions of older homebound women with regard to reaching help quickly.
AB  - The purposes of this longitudinal phenomenological study were to describe
      intentions of older women relative to reaching help quickly (RHQ), to place those
      intentions in personal-social context, and to compare intentions of subscribers
      to a personal emergency response system (PERS) and nonsubscribers. The 40
      participants were aged 85 or older, resided alone, and needed help to leave home.
      Two contextual features ("recognizing my risk of being unable to RHQ" and
      "recognizing my need for a RHQ device to sustain myself") were basic to two
      phenomena ("negotiating reliance on people to reach quickly if I need help" and
      "reducing my risk of being unable to RHQ"). There was greater variation in
      intentions and context within each of the two naturally occurring groups
      (subscribers and nonsubscribers) than between them. Practitioners cannot assume
      that women intend to use available RHQ devices in specific situations; preventive
      nursing involves proactive exploration of intentions relative to RHQ.

PMID- 22146886
TI  - Takeaway food consumption and cardio-metabolic risk factors in young adults.
AB  - BACKGROUND/OBJECTIVES: Takeaway food consumption is positively associated with
      adiposity. Little is known about the associations with other cardio-metabolic
      risk factors. This study aimed to determine whether takeaway food consumption is
      associated with fasting glucose, insulin, lipids, homeostasis model assessment
      (HOMA) and blood pressure. SUBJECTS/METHODS: A national sample of 1896, 26-36
      year olds completed a questionnaire on socio-demographics, takeaway food
      consumption, physical activity and sedentary behaviour. Waist circumference and
      blood pressure were measured, and a fasting blood sample was taken. For this
      analysis, takeaway food consumption was dichotomised to once a week or less and
      twice a week or more. Linear regression was used to calculate differences in the
      adjusted mean values for fasting lipids, glucose, insulin, HOMA and blood
      pressure. Models were adjusted for age, employment status, leisure time physical
      activity and TV viewing. RESULTS: Compared with women who ate takeaway once a
      week or less, women who ate takeaway twice a week or more had significantly
      higher adjusted mean fasting glucose (4.82 vs 4.88 mmol/l, respectively;
      P=0.045), higher HOMA scores (1.27 vs 1.40, respectively, P=0.034) and tended to
      have a higher mean fasting insulin (5.95 vs 6.45 mU/l, respectively, P=0.054).
      Similar associations were observed for men for fasting insulin and HOMA score,
      but the differences were not statistically significant. For both women and men
      adjustment for waist circumference attenuated the associations. CONCLUSION:
      Consuming takeaway food at least twice a week was associated with cardio
      metabolic risk factors in women but less so in men. The effect of takeaway food
      consumption was attenuated when adjusted for obesity.

PMID- 22146888
TI  - The value of intervening for intimate partner violence in South African primary
      care: project evaluation.
AB  - Objectives Intimate partner violence (IPV) is an important contributor to the
      burden of disease in South Africa. Evidence-based approaches to IPV in primary
      care are lacking. This study evaluated a project that implemented a South African
      protocol for screening and managing IPV. This article reports primarily on the
      benefits of this intervention from the perspective of women IPV survivors. 
      Design This was a project evaluation involving two urban and three rural primary
      care facilities. Over 4-8 weeks primary care providers screened adult women for a
      history of IPV within the previous 24 months and offered referral to the study
      nurse. The study nurse assessed and managed the women according to the protocol.
      Researchers interviewed the participants 1 month later to ascertain adherence to
      their care plan and their views on the intervention.  Results In total, 168 women
      were assisted and 124 (73.8%) returned for follow-up. Emotional (139, 82.7%),
      physical (115, 68.5%), sexual (72, 42.9%) and financial abuse (72, 42.9%) was
      common and 114 (67.9%) were at high/severe risk of harm. Adherence to the
      management plan ranged from testing for syphilis 10/25 (40.0%) to consulting a
      psychiatric nurse 28/58 (48.3%) to obtaining a protection order 28/28 (100.0%).
      Over 75% perceived all aspects of their care as helpful, except for legal advice
      from a non-profit organisation. Women reported significant benefits to their
      mental health, reduced alcohol abuse, improved relationships, increased self
      efficacy and reduced abusive behaviour. Two characteristics seemed particularly
      important: the style of interaction with the nurse and the comprehensive nature
      of the assessment.  Conclusion Female IPV survivors in primary care experience
      benefit from an empathic, comprehensive approach to assessing and assisting with
      the clinical, mental, social and legal aspects. Primary care managers should find
      ways to integrate this into primary care services and evaluate it further.

PMID- 22146887
TI  - The role of focal myocardial inflammation in sudden unexpected cardiac and
      noncardiac deaths--a clinicopathological study.
AB  - The significance of focal myocardial inflammation in sudden death is poorly
      understood, because there are few studies addressing its frequency in noncardiac
      and cardiac arrhythmic deaths. We prospectively assessed inflammation in 384
      consecutive hearts seen in consultation from a single medical examiners' office.
      Hearts were received intact and sectioned uniformly in five areas and reviewed
      histologically by a single pathologist. Intrinsic inflammatory diseases of the
      myocardium were excluded. Infiltrates were classified as lymphocytic without
      necrosis, lymphocytic with myocyte necrosis, and eosinophilic. Histologic
      findings were retrospectively correlated with other cardiac findings, history of
      drug and medication use, postmortem toxicology, and cause of death. In the 384
      hearts, any infiltrate was found in 18%. There were multifocal infiltrates in 9%,
      inflammation with necrosis in 2%, and eosinophilic myocarditis in 4%. Infiltrates
      were most frequent in natural noncardiac deaths (31%), and least frequent in
      traumatic deaths (12%). Infiltrates with myocyte necrosis occurred in 4% of
      arrhythmic deaths with no other cause, 3% of cardiac deaths with cardiomegaly, 3%
      of traumatic deaths, 2% of natural noncardiac deaths, 2% of other cardiac deaths,
      and 1% of coronary deaths. Infiltrates were common in patients on antibiotics
      (54%) or neuroleptic drugs (27%). Eosinophilic infiltrates were especially common
      in patients on antibiotics (18%). We conclude that incidental cardiac
      inflammatory infiltrates without necrosis are not uncommon, but focal
      myocarditis, defined as inflammation with necrosis, occurs in about 5% of hearts,
      and may be considered a possible contributory factor. Incidental infiltrates are
      common in patients on medications, especially antibiotics.

PMID- 22146889
TI  - Publication trends in newspapers and scientific journals for SSRIs and
      suicidality: a systematic longitudinal study.
AB  - Background In the period 2003-2008, the regulatory authorities issued several
      warnings restricting the use of selective serotonin re-uptake inhibitors (SSRIs)
      in paediatrics, in reaction to safety concerns regarding the risk of suicidality.
      In this study, the SSRIs and suicidality controversy serves as a template to
      analyse the long-term publication trends regarding the benefit/risk profile of
      medications. The aim is to ascertain differences (in terms of numbers, categories
      and timing) between negative and positive newspaper and journal articles on SSRIs
      and suicidality and to ascertain correlations between changes in the reports and
      regulatory warnings.  Methods A systematic review of scientific articles (Embase)
      and the Netherlands (NL) and the UK newspapers (LexisNexis) was performed between
      2000 and 2010. Categorisation was done by 'effect' (related treatment effect),
      'type of article' and 'age group'. The articles' positive-to-negative effect
      ratio was determined. Differences in distribution of effect categories were
      analysed across sources, type of article and age group using the Mann-Whitney
      (two subgroups) or Kruskal-Wallis test (three or more).  Findings In total, 1141
      articles were categorised: 352 scientific, 224 Dutch and 565 British newspaper
      articles. Scientific articles were predominantly on research and were positive,
      whereas newspaper articles were negative (ratios=3.50-scientific, 0.69-NL and
      0.94-UK; p<0.001). Articles on paediatrics were less positive in scientific
      journals and more negative in newspapers (ratios=2.29-scientific, 0.26-NL and
      0.20-UK; p<0.001), while articles on adults were positive overall (ratios=10.0
      scientific, 1.06-NL and 1.70-UK; p<0.001). In addition, negative-effect reporting
      trends were exacerbated following regulatory warnings and were generally opinion
      articles, both in scientific journals and in newspapers (2003/2004 and after
      2007).  Interpretation The authors found a positive publication tendency inherent
      in journal research articles. This apparent positive publication bias present in
      scientific journals, however, does not seem to prevent the dissemination of 'bad'
      news about medications. The negative tendency present in Dutch and British
      newspapers was perceivable in the paediatrics group and during the warnings,
      indicating that national news media have informed the public about this
      international drug safety controversy on time.

PMID- 22146890
TI  - Do urology journals enforce trial registration? A cross-sectional study of
      published trials.
AB  - Objectives (1) To assess endorsement of trial registration in author instructions
      of urology-related journals and (2) to assess whether randomised controlled
      trials (RCTs) in the field of urology were effectively registered.  Design Cross
      sectional study of author instructions and published trials.  Setting Journals
      publishing in the field of urology.  Participants First, the authors analysed
      author instructions of 55 urology-related journals indexed in 'Journal Citation
      Reports 2009' (12/2010). The authors divided these journals in two groups: those
      requiring and those not mentioning trial registration as a precondition for
      publication. Second, the authors chose the five journals with the highest impact
      factor (IF) from each group.  Intervention MEDLINE search to identify RCTs
      published in these 10 journals in 2009 (01/2011); search of the clinical trials
      meta-search interface of WHO (International Clinical Trials Registry Platform)
      for RCTs that lacked information about registration (01-03/2011). Two authors
      independently assessed the information.  Outcome measures Proportion of journals
      providing advice about trial registration and proportion of trials registered. 
      Results Of 55 journals analysed, 26 (47.3%) provided some editorial advice about
      trial registration. Journals with higher IFs were more likely to mention trial
      registration explicitly (p=0.015). Of 106 RCTs published in 2009, 63 were
      registered (59.4%) with a tendency to an increase after 2005 (83.3%, p=0.035).
      71.4% (30/42) of the RCTs that were published in journals mentioning and
      requiring registration, and 51.6% (33/64) of the RCTs that were published in
      journals that did not mention trial registration explicitly were registered. This
      difference was statistically significant (p=0.04).  Conclusions The existence of
      a statement about trial registration in author instructions resulted in a higher
      proportion of registered RCTs in those journals. Journals with higher IFs were
      more likely to mention trial registration.

PMID- 22146891
TI  - Age is associated with self-reported sleep bruxism, independently of tooth loss.
AB  - PURPOSE: The aim of this study was to investigate whether the association between
      self-reported sleep bruxism (SB) and age is modified by the presence of tooth
      loss. METHODS: A cross-sectional study was done involving 1,930 residents,
      ranging from 18 to 89 years of age, who underwent health checkups at the rural
      health center in Japan. The data collection included oral examinations and self
      administrated questionnaires. RESULTS: The prevalence of self-reported SB was 8%
      (n = 152). It was higher in the groups ranging from 30 to 39 and 40 to 49 years
      of age in comparison to the groups composed of individuals older than 60 years of
      age. In the crude analyses, the prevalence of self-reported SB was associated
      with tooth loss, male, smoking, snoring, sleep talking and a history of childhood
      teeth grinding. A multiple logistic regression confirmed a significant
      relationship between self-reported SB and the groups of 30-39 years of age (OR:
      2.78, P = 0.003) and 40-49 years of age (OR: 2.31, P = 0.005). Snoring (OR: 2.58,
      P = 0.001) and known (OR: 8.09, P < 0.001) or unknown (OR: 3.03 P < 0.001%)
      childhood teeth grinding also showed to be related to self-reported SB.
      CONCLUSIONS: The present study demonstrates that self-reported SB is associated
      with age, independently of tooth loss. The associations between SB and age will
      await further physiological investigations.

PMID- 22146892
TI  - Disarming suppressor cells to improve immunotherapy.
AB  - Human tumors can use many different mechanisms to induce dysfunction in the host
      immune system. Accumulations of inducible regulatory T cells (iTreg, Tr1) are
      commonly seen in the tumor microenvironment. These Treg express CD39 and up
      regulate CD73 ectonucleotidases, hydrolyze exogenous adenosine triphosphate (ATP)
      to AMP and adenosine and produce prostaglandin E(2) (PGE(2)). Most tumors also
      express CD39/CD73 and COX-2 and thus contribute to immune suppression.
      Pharmacologic inhibitors can be used to eliminate adenosine/PGE(2) production by
      Tr1 as well as the tumor or to block binding of these factors to their receptors
      on Teff or to selectively block cAMP synthesis in Teff. These pharmacologic
      blocking strategies used alone or in combination with conventional treatments or
      immunotherapies could disarm Tr1, at the same time restoring antitumor functions
      of Teff.

PMID- 22146893
TI  - An immune-active tumor microenvironment favors clinical response to ipilimumab.
AB  - PURPOSE: Ipilimumab, a fully human monoclonal antibody specific to CTLA-4, has
      been shown to improve overall survival in metastatic melanoma patients. As a
      consequence of CTLA-4 blockade, ipilimumab treatment is associated with
      proliferation and activation of peripheral T cells. To better understand various
      tumor-associated components that may influence the clinical outcome of ipilimumab
      treatment, gene expression profiles of tumors from patients treated with
      ipilimumab were characterized. EXPERIMENTAL DESIGN: Gene expression profiling was
      performed on tumor biopsies collected from 45 melanoma patients before and 3
      weeks after the start of treatment in a phase II clinical trial. RESULTS:
      Analysis of pre-treatment tumors indicated that patients with high baseline
      expression levels of immune-related genes were more likely to respond favorably
      to ipilimumab. Furthermore, ipilimumab appeared to induce two major changes in
      tumors from patients who exhibited clinical activity: genes involved in immune
      response showed increased expression, whereas expression of genes for melanoma
      specific antigens and genes involved in cell proliferation decreased. These
      changes were associated with the total lymphocyte infiltrate in tumors, and there
      was a suggestion of association with prolonged overall survival in these
      patients. Many IFN-gamma-inducible genes and Th1-associated markers showed
      increased expression after ipilimumab treatment, suggesting an accumulation of
      this particular type of T cell at the tumor sites, which might play an important
      role in mediating the antitumor activity of ipilimumab. CONCLUSIONS: These
      results support the proposed mechanism of action of ipilimumab, suggesting that
      cell-mediated immune responses play an important role in the antitumor activity
      of ipilimumab.

PMID- 22146894
TI  - [Diagnosis and treatment of Chlamydia trachomatis infections].
AB  - Nucleic acid amplification tests are now considered the method of choice to
      detect Chlamydia trachomatis. These assays have highest sensitivity and also high
      specificity, comparable to culture. First-void urine is the preferred specimen
      for urogenital infections of males, whereas vaginal and cervical swabs are at
      least as effective for testing female lower genital tract infections. Chlamydia
      point-of-care tests may produce results rapidly without special equipment but
      lack diagnostic accuracy and thus are unsuitable for routine use. Serology is not
      useful for detection of acute infections, but may help to identify persistent
      infections with Chlamydia no longer detectable in swabs or urine specimens.
      Various guidelines recommend doxycycline and azithromycin for treatment of
      uncomplicated Chlamydia infection. Alternatively erythromycin, ofloxacin and
      levofloxacin can be used. Persistent infections usually require treatment for
      longer periods or by using combinations of different antibiotics.

PMID- 22146895
TI  - [Unusual faces of syphilis].
AB  - The challenging "great masquerader" is resurgent! For several years syphilis has
      shown an increasing incidence across Europe and its variable manifestations
      necessitate its inclusion amongst many differential diagnoses. Using serological
      tests, it is possible to accurately diagnose syphilis, initiate stage-appropriate
      therapy and exclude co-infections. In this article, we feature nine unusual
      presentations of secondary syphilis. In four cases, serology confirmed HIV co
      infection.

PMID- 22146896
TI  - [Paraneoplastic palmoplantar hyperkeratosis. Minor form of acrokeratosis
      neoplastica Bazex?].
AB  - Acrokeratosis paraneoplastica Bazex is a rare, obligate paraneoplasia initially
      presenting with palmoplantar hyperkeratosis. Later stages show acral psoriasiform
      lesions on other parts of the body. Common associated malignancies are laryngeal
      cancer and other tumors of the head or neck region or neck lymph node metastases.
      A 49-year-old woman presented with palmoplantar hyperkeratoses for 4 months; in
      addition she had a squamous cell carcinoma of the larynx. We diagnosed a minor
      form of acrokeratosis paraneoplastica Bazex. Some authors consider this as a
      separate entity, but the well- known course argues against this hypothesis. We
      report a case and review the literature.

PMID- 22146897
TI  - [Surgical management of Pyoderma gangrenosum].
AB  - Pyoderma gangrenosum is a rare affection of unknown etiology, which is often
      associated with systemic diseases such as chronic inflammatory bowel disease,
      hematologic disorders, carcinomas and arthritis. Treatment may include topical
      corticosteroids or calcineurin inhibitors in combination with systemic
      corticosteroids, cyclosporine A, azathioprine, cyclophosphamide, mycophenolate
      mofetil, intravenous immunoglobulins or monoclonal antibodies against TNFalpha
      but all these approaches are off-label. Surgical therapy is difficult because of
      pathergy. Nevertheless, after having stopped the inflammation, the ulcers can be
      treated by split thickness skin grafts and simultaneous immunosuppression. We
      present three cases with successful surgical treatment.

PMID- 22146898
TI  - Spintronic platforms for biomedical applications.
AB  - Since the fundamental discovery of the giant magnetoresistance many spintronic
      devices have been developed and implemented in our daily life (e.g. information
      storage and automotive industry). Lately, advances in the sensors technology
      (higher sensitivity, smaller size) have potentiated other applications, namely in
      the biological area, leading to the emergence of novel biomedical platforms. In
      particular the investigation of spintronics and its application to the
      development of magnetoresistive (MR) biomolecular and biomedical platforms are
      giving rise to a new class of biomedical diagnostic devices, suitable for bench
      top bioassays as well as point-of-care and point-of-use devices. Herein,
      integrated spintronic biochip platforms for diagnostic and cytometric
      applications, hybrid systems incorporating magnetoresistive sensors applied to
      neuroelectronic studies and biomedical imaging, namely magneto-encephalography
      and magneto-cardiography, are reviewed. Also lab-on-a-chip MR-based platforms to
      perform biological studies at the single molecule level are discussed. Overall
      the potential and main characteristics of such MR-based biomedical devices,
      comparing to the existing technologies while giving particular examples of
      targeted applications, are addressed.

PMID- 22146900
TI  - Magnetic properties of a doped linear polyarylamine bearing a high concentration
      of coupled spins (S = 1).
AB  - Magnetic properties of a doped linear polyarylamine (PA2), whose chain includes
      alternating para-phenylene and meta-phenylene groups, and of two cyclic and
      linear model compounds (C2 and D2) were explored by pulsed-EPR nutation
      spectroscopy, SQUID magnetometry and DFT calculations. Stoichiometrically doped
      PA2 samples exhibit a pure S = 1 state (exchange coupling constant J = 18 K) with
      a high spin concentration (0.65) corresponding to 65% of mers bearing holes. Such
      properties were already observed for doped reticulated polyarylamines but are
      quite unusual for doped linear polyarylamines. In order to better understand the
      properties of PA2, model compounds C2 and D2 were also investigated: pure S = 1
      spin states could also be obtained, but with higher J (respectively 57 K and 35
      K) and, surprisingly, with high but still limited spin concentrations
      (respectively 0.77 and 0.65).

PMID- 22146899
TI  - The relations among maternal depressive disorder, maternal expressed emotion, and
      toddler behavior problems and attachment.
AB  - Direct and indirect relations among maternal depression, maternal Expressed
      Emotion (EE: Self- and Child-Criticism), child internalizing and externalizing
      symptoms, and child attachment were examined. Participants were mothers with
      depression (n = 130) and comparison mothers (n = 68) and their toddlers (M age =
      20 mo.; 53% male). Assessments included the Diagnostic Interview Schedule
      (maternal depression); the Five Minute Speech Sample (EE); the Child Behavior
      Checklist (toddler behavior problems); the Strange Situation (child attachment).
      Direct relations were significant linking: 1) maternal depression with both EE
      and child functioning; 2) Child-Criticism with child internalizing and
      externalizing symptoms; 3) Self-Criticism with child attachment. Significant
      indirect relations were found linking maternal depression with: 1) child
      externalizing behaviors via Child-Criticism; 2) child internalizing behaviors via
      Self- and Child-Criticism; and 3) child attachment via Self-Criticism. Findings
      are consistent with a conceptual model in which maternal EE mediates relations
      between maternal depression and toddler socio-emotional functioning.

PMID- 22146901
TI  - Sample pretreatment and nucleic acid-based detection for fast diagnosis utilizing
      microfluidic systems.
AB  - Recently, micro-electro-mechanical-systems (MEMS) technology and micromachining
      techniques have enabled miniaturization of biomedical devices and systems. Not
      only do these techniques facilitate the development of miniaturized
      instrumentation for biomedical analysis, but they also open a new era for
      integration of microdevices for performing accurate and sensitive diagnostic
      assays. A so-called "micro-total-analysis-system", which integrates sample
      pretreatment, transport, reaction, and detection on a small chip in an automatic
      format, can be realized by combining functional microfluidic components
      manufactured by specific MEMS technologies. Among the promising applications
      using microfluidic technologies, nucleic acid-based detection has shown
      considerable potential recently. For instance, micro-polymerase chain reaction
      chips for rapid DNA amplification have attracted considerable interest. In
      addition, microfluidic devices for rapid sample pretreatment prior to nucleic
      acid-based detection have also achieved significant progress in the recent years.
      In this review paper, microfluidic systems for sample preparation, nucleic acid
      amplification and detection for fast diagnosis will be reviewed. These
      microfluidic devices and systems have several advantages over their large-scale
      counterparts, including lower sample/reagent consumption, lower power
      consumption, compact size, faster analysis, and lower per unit cost. The
      development of these microfluidic devices and systems may provide a revolutionary
      platform technology for fast sample pretreatment and accurate, sensitive
      diagnosis.

PMID- 22146902
TI  - Management of needlestick injuries: a house officer who has a needlestick.
AB  - Since its identification in 1985, human immunodeficiency virus (HIV) has
      challenged several aspects of health care delivery. Because HIV is a blood-borne
      infectious disease, from the early days of the epidemic, concern was raised about
      risks of occupational exposures and infections among health care workers. Despite
      the development of highly active antiretroviral therapy, which has effectively
      modulated HIV into a chronic disease in many settings, risks of occupational
      infection with 3 blood-borne pathogens remain in the health care workplace. Using
      the case of a house officer who has a needlestick during a resuscitation attempt,
      prevention of needlesticks including universal precautions and postexposure
      management of occupational HIV, hepatitis B, and hepatitis C exposures is
      discussed.

PMID- 22146903
TI  - Biomarkers demonstrate increased consumption, but not abuse, of ethanol in
      essential tremor.
AB  - Ethanol is known to improve tremor in a proportion of patients with essential
      tremor. Increased incidence of alcoholism has been suspected in essential tremor
      patients; however, no objective evaluation has been performed using laboratory
      markers to date. Data on alcohol intake in the last 30 days were acquired in 95
      essential tremor patients and 35 healthy controls. Blood and urine markers
      related to alcohol metabolism and liver function were evaluated. Self-reported
      alcohol intake and biomarker levels were higher in essential tremor, but the
      difference was only significant for carbohydrate-deficient transferrin. None of
      the subjects presented with laboratory parameters reflecting chronic alcohol
      abuse. Our data do not reflect a higher incidence of alcoholism in patients with
      essential tremor. Their alcohol intake is well controlled and does not exceed the
      limits of healthy social drinking.

PMID- 22146904
TI  - Comparison of the new ASCO classification with the TOAST classification in a
      population with acute ischemic stroke.
AB  - Precise analysis of stroke subtypes is important for clinical treatment
      decisions, the prognostic evaluation of patients, as well as defining stroke
      populations in clinical studies. The TOAST classification is the most widely used
      and approved form for etiologic subtyping. Increasing knowledge about stroke
      mechanisms and the introduction of new diagnostic techniques have supported the
      promotion of the new ASCO phenotypic classification, which aims to characterize
      patients using different grades of evidence for stroke subtypes. We prospectively
      assigned 103 consecutive patients from our stroke center for subtype
      classification using ASCO and TOAST. Clinical features and complementary
      investigations were recorded according to our standardized acute stroke care
      protocol. Evidence grade 1 with ASCO was assessed in 12.62% for large artery
      disease (A), 23.30% small-vessel disease (S), 36.89% cardiac source (C) and 1.94%
      another cause (O). Evidence grades 1-3 were identified in 60.19% A, 75.73% S,
      49.51% C, and 3.88% O. A total of 68.93% of the patients were classified in more
      than one category, and only 3.88% remained completely undetermined. The kappa
      value for inter-rater agreement was 0.92-1. Using TOAST, the distribution was
      9.71% A, 23.30% S, 34.95% C, 1.94% O, and 30.10% undetermined. The ASCO
      classification showed a good concordance with TOAST. The inter-rater agreement
      was high. The comprehensive character of ASCO allows the recording of important
      additional information. This may be helpful for a specific treatment adaptation
      in each individual patient and creation of different etiological profiles in view
      of adapted clinical trials.

PMID- 22146905
TI  - Enhancing the capacity to facilitate physical activity in home-based child care
      settings.
AB  - Healthy Opportunities for Preschoolers (HOP) is a physical activity and movement
      skill intervention that was developed to address the unique needs of home-based
      child care providers. The authors used a train-the-trainer approach to enhance
      local uptake and implementation of HOP and examined the impact on the trainers'
      (workshop leaders') perceived knowledge, confidence, and intention to implement
      community workshops and subsequently on the knowledge, confidence, and intentions
      of workshop participants. This study also assessed feasibility: reach,
      satisfaction, and facilitators and barriers to workshop implementation. Overall,
      92% and 89.5% of the leaders were very or extremely satisfied with the workshop
      content and delivery, respectively. Training significantly increased their self
      reported knowledge (p < .001) and confidence (p < .001). Subsequently, 73% of
      workshop participants (48 workshops, n = 321) took part in the evaluation;
      intention to use what they learned after the workshop was high (86%) and
      perceived knowledge, confidence, and attitude all increased significantly (p <
      .001). The HOP train-the-trainer approach was feasible and enhanced knowledge,
      confidence, and readiness to change among home-based child care providers. This
      approach should be considered as a component of an overall strategy to enhance
      the promotion of physical activity and movement skills in home-based child care
      settings.

PMID- 22146906
TI  - Fulbright programs: an opportunity for career development.

PMID- 22146911
TI  - Screw-Based Motion Planning for Bevel-Tip Flexible Needles in 3D Environments
      with Obstacles.
AB  - Bevel-tip flexible needles have greater mobility than straight rigid needles, and
      can be used to reach targets behind sensitive or impenetrable areas. Accurately
      planning and executing the optimal motions for such steerable needles is
      difficult, however, and requires solving inverse kinematics for a nonholonomic
      system.This paper presents an approach to 3D motion planning for bevel-tip
      needles in an environment with obstacles. Instead of discretizing the
      configuration space as in earlier work, we discretize the control space, such
      that the trajectory of the needle can be expressed analytically without the need
      for approximate numerical simulation. This results in a fast optimization routine
      that finds a locally optimal path in a 3D environment with obstacles, requiring
      just a few seconds of computation time on a standard PC.We introduce two
      different discretization strategies that lead to differently structured paths and
      show that both produce valid trajectories from start to goal. To our knowledge,
      the presented method is the first to address motion planning for bevel-tip
      needles in a 3D environment with obstacles.

PMID- 22146912
TI  - Lead tolerance and physiological adaptation mechanism in roots of accumulating
      and non-accumulating ecotypes of Sedum alfredii.
AB  - BACKGROUND, AIM AND SCOPE: Lead (Pb) accumulation in soils affects plants
      primarily through their root systems. The aim of this study was to investigate
      early symptoms of the loss of membrane integrity and lipid peroxidation in root
      tissues and physiological adaptation mechanism to Pb in accumulating ecotypes
      (AE) and non-accumulating ecotypes (NAE) of Sedum alfredii under Pb stress in
      hydroponics. METHODS AND RESULTS: Histochemical in situ analyses, fluorescence
      imaging, and normal physiological analysis were used in this study. Pb
      accumulation in roots of both AE and NAE increased linearly with increasing Pb
      levels (0-200 MUM), and a significant difference between both ecotypes was noted.
      Both loss of plasma membrane integrity and lipid peroxidation in root tissues
      became serious with increasing Pb levels, maximum tolerable Pb level was 25 and
      100 MUM for NAE and AE, respectively. Pb supplied at a toxic level caused a burst
      of reactive oxygen species (ROS) in root cells in both ecotypes. However, the
      root cells of AE had inherently higher activities of superoxide dismutase (SOD),
      guaiacol peroxidase (POD), and lipoxygenase (LOX) in control plants, and the
      induction response of these antioxidant enzymes occurred at lower Pb level in AE
      than NAE. AE plants maintained higher ascorbic acid and H(2)O(2) concentrations
      in root cells than NAE when exposed to different Pb levels, and Pb induced more
      increase in dehydroascorbate (DHA), catalase (CAT), and ascorbate peroxidase
      (APX) in AE than NAE roots. DISCUSSION AND CONCLUSION: Results indicate that
      histochemical in situ analyses of root cell death and lipid peroxidation under Pb
      short-term stress was sensitive, reliable, and fast. Higher tolerance in roots of
      accumulating ecotype under Pb stress did depend on effective free oxygen
      scavenging by making complex function of both constitutively higher activities
      and sensitive induction of key antioxidant enzymes in root cells of S. alfredii.

PMID- 22146913
TI  - The birth and evolution of a discipline devoted to information in biomedicine and
      health care. As reflected in its longest running journal.
AB  - BACKGROUND: The journal Methods of Information in Medicine, founded in 1962, has
      now completed its 50th volume. Its publications during the last five decades
      reflect the formation of a discipline that deals with information in biomedicine
      and health care. OBJECTIVES: To report about 1) the journal's origin, 2) the
      individuals who have significantly contributed to it, 3) trends in the journal's
      aims and scope, 4) influential papers and 5) major topics published in Methods
      over the years. METHODS: Methods included analysing the correspondence and
      journal issues in the archives of the editorial office and of the publisher,
      citation analysis using the ISI and Scopus databases, and analysing the articles'
      Medical Subject Headings (MeSH) in MEDLINE. RESULTS: In the journal's first 50
      years 208 editorial board members and/or editors contributed to the journal's
      development, with most individuals coming from Europe and North America. The
      median time of service was 11 years. At the time of analysis 2,456 articles had
      been indexed with MeSH. Topics included computerized systems of various types,
      informatics methodologies, and topics related to a specific medical domain. Some
      MeSH topic entries were heavily and regularly represented in each of the
      journal's five decades (e.g. information systems and medical records), while
      others were important in a particular decade, but not in other decades (e.g.
      punched-card systems and systems integration). Seven papers were cited more than
      100 times and these also covered a broad range of themes such as knowledge
      representation, analysis of biomedical data and knowledge, clinical decision
      support and electronic patient records. CONCLUSIONS: Methods of Information in
      Medicine is the oldest international journal in biomedical informatics. The
      journal's development over the last 50 years correlates with the formation of
      this new discipline. It has and continues to stress the basic methodology and
      scientific fundamentals of organizing, representing and analysing data,
      information and knowledge in biomedicine and health care. It has and continues to
      stimulate multidisciplinary communication on research that is devoted to high
      quality, efficient health care, to quality of life and to the progress of
      biomedicine and the health sciences.

PMID- 22146914
TI  - Biomedical informatics--a confluence of disciplines?
AB  - BACKGROUND: Biomedical informatics is a broad discipline that borrows many
      methods and techniques from other disciplines. OBJECTIVE: To reflect a) on the
      character of biomedical informatics and to determine whether it is multi
      disciplinary or inter-disciplinary; b) on the question whether biomedical
      informatics is more than the sum of its supporting disciplines and c) on the
      position of biomedical informatics with respect to related disciplines. METHOD:
      Inviting an international group of experts in biomedical informatics and related
      disciplines on the occasion of the 50th anniversary of Methods of Information in
      Medicine to present their viewpoints. RESULTS AND CONCLUSIONS: This paper
      contains the reflections of a number of the invited experts on the character of
      biomedical informatics. Most of the authors agree that biomedical informatics is
      an interdisciplinary field of study where researchers with different scientific
      backgrounds alone or in combination carry out research. Biomedical informatics is
      a very broad scientific field and still expanding, yet comprised of a
      constructive aspect (designing and building systems). One author expressed that
      the essence of biomedical informatics, as opposed to related disciplines, lies in
      the modelling of the biomedical content. Interdisciplinarity also has
      consequences for education. Maintaining rigid disciplinary structures does not
      allow for sufficient adaptability to capitalize on important trends nor to
      leverage the influences these trends may have on biomedical informatics. It is
      therefore important for students to become aware of research findings in related
      disciplines. In this respect, it was also noted that the fact that many
      scientific fields use different languages and that the research findings are
      stored in separate bibliographic databases makes it possible that potentially
      connected findings will never be linked, despite the fact that these findings
      were published. Bridges between the sciences are needed for the success of
      biomedical informatics.

PMID- 22146915
TI  - 50 years of informatics research on decision support: what's next.
AB  - OBJECTIVES: To reflect on the history, status, and future trends of decision
      support in health and biomedical informatics. To highlight the new challenges
      posed by the complexity and diversity of genomic and clinical domains. To examine
      the emerging paradigms for supporting cost-effective, personalized decision
      making. METHODS: A group of international experts in health and biomedical
      informatics presented their views and discussed the challenges and issues on
      decision support at the Methods of Information in Medicine 50th anniversary
      symposium. The experts were invited to write short articles summarizing their
      thoughts and positions after the symposium. RESULTS AND CONCLUSIONS: The
      challenges posed by the complexity and diversity of the domain knowledge, system
      infrastructure, and usage pattern are highlighted. New requirements and
      computational paradigms for representing, using, and acquiring biomedical
      knowledge and healthcare protocols are proposed. The underlying common themes
      identified for developing next-generation decision support include incorporating
      lessons from history, uniform vocabularies, integrative interfaces,
      contextualized decisions, personalized recommendations, and adaptive solutions.

PMID- 22146916
TI  - Data analysis and data mining: current issues in biomedical informatics.
AB  - BACKGROUND: Medicine and biomedical sciences have become data-intensive fields,
      which, at the same time, enable the application of data-driven approaches and
      require sophisticated data analysis and data mining methods. Biomedical
      informatics provides a proper interdisciplinary context to integrate data and
      knowledge when processing available information, with the aim of giving effective
      decision-making support in clinics and translational research. OBJECTIVES: To
      reflect on different perspectives related to the role of data analysis and data
      mining in biomedical informatics. METHODS: On the occasion of the 50th year of
      Methods of Information in Medicine a symposium was organized, which reflected on
      opportunities, challenges and priorities of organizing, representing and
      analysing data, information and knowledge in biomedicine and health care. The
      contributions of experts with a variety of backgrounds in the area of biomedical
      data analysis have been collected as one outcome of this symposium, in order to
      provide a broad, though coherent, overview of some of the most interesting
      aspects of the field. RESULTS: The paper presents sections on data accumulation
      and data-driven approaches in medical informatics, data and knowledge
      integration, statistical issues for the evaluation of data mining models,
      translational bioinformatics and bioinformatics aspects of genetic epidemiology.
      CONCLUSIONS: Biomedical informatics represents a natural framework to properly
      and effectively apply data analysis and data mining methods in a decision-making
      context. In the future, it will be necessary to preserve the inclusive nature of
      the field and to foster an increasing sharing of data and methods between
      researchers.

PMID- 22146917
TI  - Confluence of disciplines in health informatics: an international perspective.
AB  - OBJECTIVE: To discuss international aspects as they relate to the convergence of
      disciplines in health informatics. METHOD: A group of international experts was
      invited at a symposium to present and discuss their perspectives on this topic.
      These have been collated in a single manuscript. RESULTS AND CONCLUSIONS:
      Significant challenges, as well as opportunities, appear when cumulating the
      intrinsic multidisciplinary nature of health informatics interventions with the
      diversity of contexts at the global level, in particular when considered in the
      perspective of a confluence, i.e., the mixing of different waters and their
      merging into a new, stronger entity. Health informatics experts reflect on key
      issues such as collaborative software development and distributed knowledge
      sourcing, social media and mobile technologies, the evolutions of the discipline
      from an historical perspective, as well as examples of challenges for
      implementing ubiquitous healthcare or for supporting disaster situations when
      infrastructures get disrupted.

PMID- 22146918
TI  - Compatible immuno-NASBA LOC device for quantitative detection of waterborne
      pathogens: design and validation.
AB  - Waterborne pathogens usually pose a global threat to animals and human beings.
      There has been a growing demand for convenient and sensitive tools to detect the
      potential emerging pathogens in water. In this study, a lab-on-a-chip (LOC)
      device based on the real-time immuno-NASBA (immuno-nucleic acid sequence-based
      amplification) assay was designed, fabricated and verified. The disposable immuno
      NASBA chip is modelled on a 96-well ELISA microplate, which contains 43 reaction
      chambers inside the bionic channel networks. All valves are designed outside the
      chip and are reusable. The sample and reagent solutions were pushed into each
      chamber in turn, which was controlled by the valve system. Notably, the immuno
      NASBA chip is completely compatible with common microplate readers in a
      biological laboratory, and can distinguish multiple waterborne pathogens in water
      samples quantitatively and simultaneously. The performance of the LOC device was
      demonstrated by detecting the presence of a synthetic peptide, ACTH
      (adrenocorticotropic hormone) and two common waterborne pathogens, Escherichia
      coli (E. coli) and rotavirus, in artificial samples. The results indicated that
      the LOC device has the potential to quantify traces of waterborne pathogens at
      femtomolar levels with high specificity, although the detection process was still
      subject to some factors, such as ribonuclease (RNase) contamination and non
      specific adsorption. As an ultra-sensitive tool to quantify waterborne pathogens,
      the LOC device can be used to monitor water quality in the drinking water system.
      Furthermore, a series of compatible high-throughput LOC devices for monitoring
      waterborne pathogens could be derived from this prototype with the same design
      idea, which may render the complicated immuno-NASBA assays convenient to common
      users without special training.

PMID- 22146920
TI  - Three tough acts to follow.

PMID- 22146919
TI  - Plate fixation versus intramedullary fixation for displaced mid-shaft clavicle
      fractures: a systematic review.
AB  - PURPOSE: The optimal surgical approach for displaced midshaft clavicle fracture
      remains controversial. The objective of this systematic review is to compare
      functional outcome and complications after plate fixation and intramedullary
      fixation for displaced midshaft clavicle fractures. METHODS: A computer aided
      search of PUBMED and Embase was carried out on January 11th 2011. Every study
      that was published in the English, German, French or Dutch language was
      considered for inclusion. A total of four studies could be included of which two
      compared intramedullary fixation versus plate fixation, and two compared
      intramedullary fixation and plate fixation versus conservative treatment for
      displaced midshaft clavicle fractures. Studies that compared plate fixation with
      intramedullary fixation in patients with fresh unilateral displaced midshaft
      clavicle fractures were included. Dislocation or displacement had to be mentioned
      in the inclusion criteria of the study for inclusion in this review. The modified
      version of the Cochrane Bone, Joint and Muscle Trauma Group's former quality
      assessment tool was used. Furthermore, the studies included were scored according
      to the GRADE approach to assess the quality. The chosen studies were summarised
      in a data-extraction form. Because of the different study designs and
      characteristics data were summarised separately for each study. CONCLUSIONS: High
      quality evidence from one study and low quality evidence from three studies
      showed no difference in functional outcome or complications after plate fixation
      or intramedullary fixation for displaced midshaft clavicle fractures.

PMID- 22146921
TI  - Neurocognitive abilities in young adults with very low birth weight.
AB  - OBJECTIVE: Although severely preterm birth has been associated with impaired
      neurocognitive abilities in children, follow-up studies in adulthood are scarce.
      We set out to study whether adults born with very low birth weight (VLBW) (<1,500
      g), either small for gestational age (SGA) (birth weight <=-2 SD) or appropriate
      for gestational age (AGA), differ in a range of neurocognitive abilities and
      academic performance from adults born at term and not SGA. METHODS: As part of
      the Helsinki Study of Very Low Birth Weight Adults, 103 VLBW (37 SGA) and 105
      term-born control adults (mean age 25.0, range 21.4-29.7 years) without major
      neurosensory impairments participated in the follow-up study in 2007-2008. The
      test battery included measures of general cognitive ability as well as executive
      functioning and related abilities. Academic performance was self-reported.
      RESULTS: With adjustment for sex and age, the VLBW group scored lower or
      performed slower than the control group in some indices of all tests (these mean
      differences ranged from 0.3 to 0.5 SD units, p <= 0.03) and they had received
      remedial education at school more frequently; however, no differences existed in
      self-reported academic performance. The differences were evident in both VLBW-SGA
      and VLBW-AGA groups. Further covariate adjustments for parental education,
      current head circumference, and head circumference at birth and, in tests of
      executive functioning and related abilities, adjustment for IQ estimate had minor
      effects on the results. CONCLUSIONS: In comparison with control adults, VLBW
      adults scored lower on several neurocognitive tests. Poorer neurocognitive
      performance is associated with VLBW irrespective of the intrauterine growth
      pattern.

PMID- 22146922
TI  - The 2011 UN General Assembly on noncommunicable diseases: how neurologic
      disorders got left out.

PMID- 22146923
TI  - Spontaneous rupture of intracranial dermoid cyst in a child.

PMID- 22146924
TI  - Psychogenic dystonia and peripheral trauma.

PMID- 22146925
TI  - Statin use and outcome after intracerebral hemorrhage: case-control study and
      meta-analysis.

PMID- 22146927
TI  - Teaching NeuroImages: isolated cervical spinal cord cysticercosis.

PMID- 22146928
TI  - Teaching NeuroImages: a slowly growing benign brain mass.

PMID- 22146929
TI  - Methylphenidate for gait impairment in Parkinson disease: a randomized clinical
      trial.

PMID- 22146930
TI  - Reproductive numbers for nonautonomous spatially distributed periodic SIS models
      acting on two time scales.
AB  - In this work we deal with a general class of spatially distributed periodic SIS
      epidemic models with two time scales. We let susceptible and infected individuals
      migrate between patches with periodic time dependent migration rates. The
      existence of two time scales in the system allows to describe certain features of
      the asymptotic behavior of its solutions with the help of a less dimensional,
      aggregated, system. We derive global reproduction numbers governing the general
      spatially distributed nonautonomous system through the aggregated system. We
      apply this result when the mass action law and the frequency dependent
      transmission law are considered. Comparing these global reproductive numbers to
      their non spatially distributed counterparts yields the following: adequate
      periodic migration rates allow global persistence or eradication of epidemics
      where locally, in absence of migrations, the contrary is expected.

PMID- 22146931
TI  - The microwave cavity perturbation technique for contact-free and in situ
      electrical conductivity measurements in catalysis and materials science.
AB  - We have developed a noncontact method to probe the electrical conductivity and
      complex permittivity of single and polycrystalline samples in a flow-through
      reactor in the temperature range of 20-500  degrees C and in various gas
      atmospheres. The method is based on the microwave cavity perturbation technique
      and allows the simultaneous measurement of microwave conductivity, permittivity
      and of the catalytic performance of heterogeneous catalysts without any need for
      contacting the sample with electrodes. The sensitivity of the method towards
      changes in bulk properties was proven by the investigation of characteristic
      first-order phase transitions of the ionic conductor rubidium nitrate in the
      temperature range between 20 and 320  degrees C, and by studying the temperature
      dependence of the complex permittivity and conductivity of a niobium(V)-doped
      vanadium-phosphorous-oxide catalyst for the selective oxidation of n-butane to
      maleic anhydride. Simultaneously, the catalytic performance was probed by on line
      GC analysis of evolving product gases making the technique a real in situ method
      enabling the noninvasive investigation of electronic structure-function
      relationships.

PMID- 22146932
TI  - Clinical and laboratory data in a sample of Greek children with autism spectrum
      disorders.
AB  - The purpose of this study is to describe clinical and laboratory data, as well as
      comorbid disorders in Greek children with autism spectrum disorders (ASD). Data
      were retrospectively collected for 222 children aged 1.5-9 years. The mean age at
      diagnosis was 43.7 +/- 17.6 months. Significantly earlier diagnoses were noted in
      children with comorbid disorders (epilepsy, hearing deficits, genetic/metabolic
      disorders), mental retardation and a large head circumference (HC). Macrocephaly
      (HC >= 97th percentile) was found in 21.2% of children, genetic and metabolic
      disorders in 11.7% and 2.7% respectively and mental retardation in 23%. Patients
      with certain clinical features (i.e. syndromic) are earlier diagnosed. It is of
      ultimate importance to promptly identify all children with ASD, probably through
      the appliance of screening and surveillance programs in the Greek population.

PMID- 22146933
TI  - Goal-directed and goal-less imitation in autism spectrum disorder.
AB  - To investigate how people with Autism are affected by the presence of goals
      during imitation, we conducted a study to measure movement kinematics and eye
      movements during the imitation of goal-directed and goal-less hand movements. Our
      results showed that a control group imitated changes in movement kinematics and
      increased the level that they tracked the hand with their eyes, in the goal-less
      compared to goal-direction condition. In contrast, the ASD group exhibited more
      goal-directed eye movements, and failed to modulate the observed movement
      kinematics successfully in either condition. These results increase the evidence
      for impaired goal-less imitation in ASD, and suggest that there is a reliance on
      goal-directed strategies for imitation in ASD, even in the absence of visual
      goals.

PMID- 22146934
TI  - Brief report: effect of a focused imitation intervention on social functioning in
      children with autism.
AB  - Imitation is an early skill thought to play a role in social development, leading
      some to suggest that teaching imitation to children with autism should lead to
      improvements in social functioning. This study used a randomized controlled trial
      to evaluate the effect of a focused imitation intervention on initiation of joint
      attention and social-emotional functioning in 27 young children with autism.
      Results indicated the treatment group made significantly more gains in joint
      attention initiations at post-treatment and follow-up and social-emotional
      functioning at follow-up than the control group. Although gains in social
      functioning were associated with treatment, a mediation analysis did not support
      imitation as the mechanism of action. These findings suggest the intervention
      improves social functioning in children with ASD.

PMID- 22146935
TI  - [Risk factor "smoking" : smoking cessation in patients with cardiovascular
      diseases].
AB  - Smoking is the most frequent cause of avoidable premature death. Annually, almost
      6 million people die due to nicotine consumption. Comparing modifiable
      cardiovascular risk factors, smoking has the strongest impact on cardiovascular
      mortality. More than 50% of all premature myocardial infarctions are related to
      nicotine consumption. Even in patients with known coronary disease receiving
      optimal medical therapy, there is a remarkable additional preventive effect of
      smoking cessation detectable. Therefore, smoking cessation is an essential
      component of primary and secondary prevention strategies. Smoking cessation
      programs applying a combination of behavior therapy and supporting medical
      treatment have been demonstrated to be the most effective.

PMID- 22146936
TI  - [Stereotypical episodes of vomiting for 11 years in a 33-year-old patient].
AB  - A 33-year-old man was admitted because of severe vomiting. For the last 11 years,
      he had suffered recurrent stereotypical episodes of vomiting lasting 3-4 days.
      The episodes of vomiting occurred 10-15 times a year. Moreover his brother and
      his mother had similar symptoms. Thus, (familial) cyclic vomiting syndrome was
      diagnosed. With the help of antiemetic and sedative drugs, the acute vomiting
      episode was stopped. Prophylactic therapy with amitriptyline was started, which
      led to a symptom-free period of 3.5 years without a new episode of vomiting.

PMID- 22146937
TI  - [Anticoagulation for atrial fibrillation : the future has begun].
AB  - According to new criteria based on the CHAD(2)DS(2)-VASc score, the threshold for
      administering anticoagulation therapy for atrial fibrillation patients is being
      increasingly lowered. With the development of new anticoagulants, more therapy
      options are available. Currently, vitamin K antagonists are still the standard
      treatment. However, this therapy is problematic for some patients. Because of the
      increased bleeding risk and need for continuous blood tests to monitor
      coagulation, many patients needing anticoagulation therapy are not treated. The
      new anticoagulants apixaban, rivaroxaban and dabigatran were developed with the
      goal of avoiding these problems. Dabigatran has already been approved for
      thromboembolism prophylaxis for patients with atrial fibrillation. All three
      substances do not require routine control blood tests. Whether the costs saved by
      this together with the prevention of ischemic and bleeding events justify the
      higher price of these drugs compared to vitamin K antagonists needs to be
      examined by socioeconomic studies.

PMID- 22146938
TI  - Vacuolar-type H+-ATPase-mediated proton transport in the rat parietal cell.
AB  - The vacuolar-type H-ATPase (V-ATPase) plays an important role in the active
      acidification of intracellular organelles. In certain specialized cells, such as
      the renal intercalated cell, apical V-ATPase can also function as a proton
      secretion pathway. In the parietal cells of the stomach, it has been thought that
      acid secretion is controlled solely via the H,K-ATPase. However, recent
      observations suggest that functional V-ATPase is necessary for acid secretion to
      take place. This study aimed to investigate and characterize the role of V-ATPase
      in parietal cell proton transport. Individual rat gastric glands were incubated
      with the pH-sensitive dye (BCECF) to monitor changes in intracellular pH in real
      time. Parietal cell V-ATPase activity was measured by quantifying the rate of
      intracellular alkalinization (DeltapH/minute) following an acid load, while
      excluding the contribution of non-V-ATPase proton transport mechanisms through
      pharmacological inhibition or ion substitution. Expression of V-ATPase was
      confirmed by immunohistochemistry. We observed concanamycin A-sensitive V-ATPase
      activity in rat parietal cells following intracellular acidification and H,K
      ATPase inhibition. Furthermore, V-ATPase-mediated proton transport could be
      abolished by inhibiting trafficking mechanisms with paclitaxel and by stimulating
      H,K-ATPase with acid secretagogues. Our results propose that parietal cells
      contain a functional V-ATPase that can be mobilized using a microtubule network.
      V-ATPase may function as an auxiliary acid secretion or proton-buffering pathway
      in parietal cells, which is inactive during H,K-ATPase activity. Our findings may
      have important implications for patients experiencing acid breakthrough under
      proton pump inhibitor therapy.

PMID- 22146940
TI  - Skewed X inactivation and survival: a 13-year follow-up study of elderly twins
      and singletons.
AB  - In mammalian females, one of the two X chromosomes is inactivated in early
      embryonic life. Females are therefore mosaics for two cell populations, one with
      the maternal and one with the paternal X as the active X chromosome. A skewed X
      inactivation is a marked deviation from a 50:50 ratio. In populations of women
      past 55-60 years of age, an increased degree of skewing (DS) is found. Here the
      association between age-related skewing and mortality is analyzed in a 13-year
      follow-up study of 500 women from three cohorts (73-100 years of age at intake).
      Women with low DS had significantly higher mortality than the majority of women
      who had a more skewed DS (hazard ratio: 1.30; 95% CI: 1.04-1.64). The association
      between X inactivation and mortality was replicated in dizygotic twin pairs for
      which the co-twin with the lowest DS also had a statistically significant
      tendency to die first in the twin pairs with the highest intra-pair differences
      in DS (proportion: 0.71; 95% CI: 0.52-0.86). Both results suggest that lower DS
      is associated with higher mortality. We therefore propose that age-related
      skewing may be partly due to a population selection with lower mortality among
      those with higher DS.

PMID- 22146941
TI  - 'Nasal' speech--hyper or hypo?

PMID- 22146942
TI  - Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty
      acid hydroxylase-associated neurodegeneration.
AB  - Fatty acid hydroxylase-associated neurodegeneration due to fatty acid 2
      hydroxylase deficiency presents with a wide range of phenotypes including spastic
      paraplegia, leukodystrophy, and/or brain iron deposition. All previously
      described families with this disorder were consanguineous, with homozygous
      mutations in the probands. We describe a 10-year-old male, from a non
      consanguineous family, with progressive spastic paraplegia, dystonia, ataxia, and
      cognitive decline associated with a sural axonal neuropathy. The use of high
      throughput sequencing techniques combined with SNP array analyses revealed a
      novel paternally derived missense mutation and an overlapping novel maternally
      derived ~28-kb genomic deletion in FA2H. This patient provides further insight
      into the consistent features of this disorder and expands our understanding of
      its phenotypic presentation. The presence of a sural nerve axonal neuropathy had
      not been previously associated with this disorder and so may extend the
      phenotype.

PMID- 22146943
TI  - Enhanced recovery program following colorectal resection in the elderly patient.
AB  - BACKGROUND: The enhanced recovery program (ERP) aims to reduce the metabolic
      response to surgery, hastening recovery and shortening hospital stay. Concerns
      exist regarding morbidity and hospital stay in elderly patients. The present
      study aimed to compare the outcomes and compliance of elderly patients managed by
      an ERP protocol with a younger group. METHODS: A review was performed of a
      prospective database of patients undergoing colorectal resection managed under
      the ERP protocol between 2005 and 2010. Patients were grouped into <80 years and
      >= 80 years, and perioperative data were collated. The postoperative outcomes
      were compared with the goals set out by the ERP protocol. RESULTS: A total of 688
      patients were included, 558 were <80 years (median: 66 years; range: 17-79 years)
      and 130 were >= 80 years (median: 83 years; range: 80-95 years). Some 96% of
      operations were planned laparoscopically. Median total length of hospital stay
      was 6 days (range: 1-108 days) for the <80 year group and 8 days (range: 1-167
      days; P 0.363) for the elderly group, with a 30 day readmission rate of 8.6% for
      the population and no significant differences between groups. The 30 day
      mortality was 5%, with a significant difference between the two groups (P <
      0.0001). Differences in protocol adherence were identified in the discontinuation
      of intravenous fluids, catheter removal, and early mobilization. CONCLUSIONS: An
      enhanced recovery program is feasible for colorectal surgery patients >= 80 years
      of age, with similar compliance as the younger group to some aspects of the
      protocol and an acceptable readmission rate. Attention to improving compliance in
      the postoperative phase is necessary, particularly in such high-risk patients, as
      such improvement may reduce the morbidity and mortality.

PMID- 22146944
TI  - Clinical implication of serosal change in pathologic subserosa-limited gastric
      cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical implication of
      serosal change in pathologic subserosa-limited gastric cancer based on a
      retrospective analysis. METHODS: A total of 285 patients who were diagnosed with
      pathologically subserosa-limited gastric cancer were included. The patients were
      divided into two groups: the accordance group, with subserosa-limited cancer
      without macroscopic serosa change (n = 124); the discordance group, with
      subserosa-limited cancer showing macroscopic serosal change (n = 161). RESULTS:
      Tumor size, number of metastatic lymph nodes, and pathologic N stage were
      significantly associated with macroscopic serosal change. Serosal change patients
      presented a higher recurrence rate compared with patients without serosal change
      (38.0 vs. 20.2% for the 5-year recurrence rate, P = 0.002), and peritoneal
      seeding presented frequently in serosal-change patients with significance
      (41.1%). Likewise, the overall survival of serosal-change patients was
      significantly worse than that for those without serosal change (66.9 vs. 81.4%
      for the 5-year survival rate, P = 0.002). Serosal change was an independent
      prognostic factor for overall survival (relative risk 1.784, P = 0.039).
      CONCLUSIONS: Serosal change in pathologic subserosa-limited gastric cancer is
      related to poor survival. Therefore, adjuvant chemotherapy should be considered
      for these patients, and adequate follow-up programs instituted for early
      detection of peritoneal seeding.

PMID- 22146945
TI  - Management of delayed presentation of a right-side traumatic diaphragmatic
      rupture.
AB  - BACKGROUND: Right-side diaphragmatic rupture is an unusual condition after blunt
      trauma. The diagnosis may be missed during the early period of trauma and may
      lead to progressive herniation of intraabdominal contents into the thorax. In
      this study, we aimed to evaluate the diagnosis and treatment options for the late
      diagnosis of cases of right-side traumatic diaphragmatic rupture. METHODS: We
      evaluated the patients with diaphragmatic hernia who were admitted to the
      hospital during an 8-year period. Only patients with a right-side diaphragmatic
      hernia and a history of high-energy trauma were included in the study. Patients
      with left-side diaphragmatic hernia or those who were subjected to emergency
      operation due to diaphragmatic rupture were excluded from the study. Patient
      characteristics, clinical presentations, diagnostic tools, and treatment options
      were evaluated. RESULTS: Eight patients (five men, three women) were enrolled in
      the study. The most common trauma type was a traffic accident, and the average
      interval between the trauma and diagnosis was 10 years. Thoracoabdominal computed
      tomography had high sensitivity and specificity for visualizing the diaphragmatic
      hernia. No predisposing factor was found to add laparotomy to thoracotomy. There
      was no postoperative mortality, and no late complications were observed at the
      assessments during the 45-month follow-up. CONCLUSIONS: Clinical presentation of
      late diagnosed diaphragmatic hernia, which is encountered only rarely on the
      right side, requires diagnostic and therapeutic approaches different from those
      associated with acute diaphragmatic rupture. It should not be forgotten during
      the differential diagnosis in patients with a history of trauma.

PMID- 22146946
TI  - Combination of dexamethasone and tropisetron before thyroidectomy to alleviate
      postoperative nausea, vomiting, and pain: randomized controlled trial.
AB  - BACKGROUND: Nausea, vomiting, and pain frequently occur after thyoidectomy.
      Little evidence exists regarding the effects of administrating a combination of
      dexamethasone and tropisetron to patients undergoing thyroidectomy. We aimed to
      evaluate the effects of dexamethasone and tropisetron on thyroidectomy outcomes.
      METHODS: A total of 150 patients undergoing thyroidectomy were included in this
      prospective randomized, controlled, three-arm study (group D: 8 mg dexamethasone;
      group T: 5 mg tropisetron; group D+T: 8 mg dexamethasone and 5 mg tropisetron).
      There were 50 patients in each group. Nausea, vomiting, pain, and the amount of
      antiemetic and analgesic agents required were recorded 2, 4, 8, 16, 24, 36, and
      48 h postoperatively. RESULTS: The complete response rate of nausea and vomiting
      was significantly higher in group D+T (78%, 39/50), compared with that in group D
      (58%, 29/50) or group T (66%, 33/50) (P = 0.01). The incidence and severity of
      nausea in group D+T were significantly lower than in group D and group T, with
      the difference mainly occurring in the late postoperative period (6-48 h). The
      severity of postoperative pain was significantly less in the dexamethasone
      containing groups (D and D+T groups) than in the tropisetron group. CONCLUSIONS:
      The combination of dexamethasone and tropisetron offers better prophylaxis for
      nausea, vomiting, and pain than either drug alone in patients undergoing
      thyroidectomy, especially during the late period (6-48 h).

PMID- 22146947
TI  - Parathyroid four-dimensional computed tomography: evaluation of radiation dose
      exposure during preoperative localization of parathyroid tumors in primary
      hyperparathyroidism.
AB  - BACKGROUND: Parathyroid four-dimensional computed tomography (4DCT) provides
      greater sensitivity than sestamibi with single photon emission CT (SPECT, or SeS)
      for preoperative localization of parathyroid tumors in patients with primary
      hyperparathyroidism (PHPT). The radiation dose imparted to the patient during
      preoperative parathyroid imaging, however, has not been analyzed. METHODS:
      Patients with biochemically unequivocal PHPT referred for minimally invasive
      parathyroidectomy underwent 4DCT or SeS. 4DCT was performed using a 64 detector
      row CT scanner, and SeS used a standardized protocol of 20 mCi of technetium-99m
      followed by planar and SPECT imaging. The CT radiation dose was estimated using
      the Imaging Performance Assessment of CT Scanners (ImPACT) calculator, and the
      SeS dose was estimated using the US Nuclear Regulatory Commission Regulation
      (NUREG) method. RESULTS: The calculated effective doses of 4DCT and SeS were 10.4
      and 7.8 mSv, respectively, in contrast to an estimated annual background
      radiation exposure of approximately 3 mSv. The dose to the thyroid with 4DCT,
      however, was about 57 times higher (92.0 vs. 1.6 mGy) than that with SeS. Based
      on age- and sex-dependent risk factors, the calculated risk of 4DCT-related
      thyroid cancer developing in a 20 year old woman was 1,040/million (i.e., about
      0.1%). CONCLUSIONS: 4DCT, a superior preoperative imaging modality for locating
      parathyroid tumors, imparts a significantly higher thyroid radiation dose than
      SeS. Given the enhanced risk of thyroid cancer in individuals with radiation
      exposure at a young age, 4DCT should be used judiciously in young PHPT patients.

PMID- 22146948
TI  - Microfluidic wound-healing assay to assess the regenerative effect of HGF on
      wounded alveolar epithelium.
AB  - We present a microfluidic epithelial wound-healing assay that allows
      characterization of the effect of hepatocyte growth factor (HGF) on the
      regeneration of alveolar epithelium using a flow-focusing technique to create a
      regular wound in the epithelial monolayer. The phenotype of the epithelial cell
      was characterized using immunostaining for tight junction (TJ) proteins and
      transmission electron micrographs (TEMs) of cells cultured in the microfluidic
      system, a technique that is reported here for the first time. We demonstrate that
      alveolar epithelial cells cultured in a microfluidic environment preserve their
      phenotype before and after wounding. In addition, we report a wound-healing
      benefit induced by addition of HGF to the cell culture medium (19.2 vs. 13.5 MUm
      h(-1) healing rate).

PMID- 22146949
TI  - Towards better photocatalysts: first-principles studies of the alloying effects
      on the photocatalytic activities of bismuth oxyhalides under visible light.
AB  - Via density functional theory computations, we investigated the photocatalytic
      activities of pure and alloyed bismuth oxyhalides (BiOXs). The dipole moments of
      the majority of pure and alloyed BiOXs are larger than 2.00 Debye, which can
      ensure their high photocatalytic efficiencies. Both the redox potentials of the
      photon-induced holes and the band gaps increase with an increasing content of
      lighter halogen atoms in the BiOXs, which competitively affects the
      photocatalytic efficiency. The hole mobility decreases a lot due to the
      hybridization of the halogen np states, while the electron mobility is not
      affected by such hybridization. Therefore, the alloying effect in BiOXs brings
      about a substantially lower electron-hole recombination rate and, accordingly, a
      much higher photocatalytic efficiency. Our investigation also suggests that O
      vacancies, which are energetically more favorable in alloyed BiOXs, could act as
      capture centers for excited electrons and, consequently, improve the separation
      of the electron-hole pairs. Our findings present a reasonable explanation for the
      recent experimental reports and provide some guidance for the design of alloyed
      BiOX photocatalysts.

PMID- 22146951
TI  - Anthraquinones from the bark of Senna macranthera.
AB  - 2-acetyl physcion (2-acetyl-1,8-dihydroxy-6-methoxy-3-methyl-9,10-anthraquinone,
      2), a rare anthraquinone, was isolated from Senna macranthera var. nervosa
      (Vogel) H.S. Irwin & Barneby (Fabaceae). The chemical structure was elucidated
      and all (1)H and (13)C NMR chemical shifts were assigned by NMR one- ((1)HNMR,
      {(1)H}-(13)CNMR, and APT-(13)CNMR) and two (COSY, NOESY, HMQC and HMBC)
      dimensional of this natural compound. Furthermore, the minor anthraquinones
      chrysophanol (3), chrysophanol-8-methyl ether (4) and physcion (5) were
      characterized by GC-MS analysis. The occurrence of the anthraquinones 3-5
      confirms that S. macranthera is a typical representative of the genus Senna.

PMID- 22146952
TI  - Chemical composition fluctuations in roots of Plumbago scandens L. in relation to
      floral development.
AB  - Plumbago scandens L. is a Brazilian tropical/subtropical species that occurs
      along the coast. Chemically it is mainly represented by naphthoquinones,
      flavonoids, terpenoids and steroids. The aim of the present work is to study
      quantitative changes in the root metabolic production of Plumbago scandens during
      different physiologic developmental stages relative to floration. The results
      indicated the presence of four substances in the extracts: plumbagin, epi
      isoshinanolone, palmitic acid and sitosterol, independent on developmental stage.
      The naphthoquinone plumbagin has always showed to be the major component of all
      extracts. Naphthoquinones exhibited their highest content during floration, while
      the content of the two others components decreased during this stage, revealing
      an inverse profile. The chemical composition changed depending on the plant
      requirements.

PMID- 22146953
TI  - A new genus of dipnoiformes from the Cretaceous of Brazil.
AB  - The Alcantara Formation, an important stratigraphic unit from the early
      Cenomanian of Brazil, was deposited under transitional (estuarine) conditions,
      and its fossil record includes fragmentary remains of plants, fishes,
      crocodylomorphs, pterosaurs and dinosaurs, with a noteworthy diversity of
      dipnoiformes tooth plates. The dipnoiformes material reported here comprises a
      new taxon, Equinoxiodus alcantarensis, gen. et sp. nov. Most of the identified
      morphotypes of continental vertebrates collected in the Alcantara Formation are
      similar to chronocorrelative faunas from Northern Africa, but this new genus of
      Dipnoiformes indicates some degree of paleogeographic isolation and endemism.
      This was probably caused by the widening of the equatorial Atlantic Ocean during
      the early Cenomanian, which may have selectively affected some species.

PMID- 22146955
TI  - Modeling radiative transfer in tropical rainforest canopies: sensitivity of
      simulated albedo to canopy architectural and optical parameters.
AB  - This study evaluates the sensitivity of the surface albedo simulated by the
      Integrated Biosphere Simulator (IBIS) to a set of Amazonian tropical rainforest
      canopy architectural and optical parameters. The parameters tested in this study
      are the orientation and reflectance of the leaves of upper and lower canopies in
      the visible (VIS) and near-infrared (NIR) spectral bands. The results are
      evaluated against albedo measurements taken above the K34 site at the INPA
      (Instituto Nacional de Pesquisas da Amazonia) Cuieiras Biological Reserve. The
      sensitivity analysis indicates a strong response to the upper canopy leaves
      orientation (chiup) and to the reflectivity in the near-infrared spectral band
      (rhoNIR,up), a smaller sensitivity to the reflectivity in the visible spectral
      band (rhoVIS,up) and no sensitivity at all to the lower canopy parameters, which
      is consistent with the canopy structure. The combination of parameters that
      minimized the Root Mean Square Error and mean relative error are chiup = 0.86,
      rhoVIS,up = 0.062 and rhoNIR,up = 0.275. The parameterizations performed resulted
      in successful simulations of tropical rainforest albedo by IBIS, indicating its
      potential to simulate the canopy radiative transfer for narrow spectral bands and
      permitting close comparison with remote sensing products.

PMID- 22146956
TI  - A new ctenochasmatid pterosaur from the Lower Cretaceous, western Liaoning,
      China.
AB  - A nearly complete skull of a new ctenochasmatid pterosaur, Pterofiltus qiui gen.
      et sp. nov., from the Lower Cretaceous deposits of Liaoning, China, is described
      here. The specimen (IVPP V12339), was collected from the shale of the lower
      Yixian Formation (125 Ma) at the Zhangjiagou locality. It has the following
      combination of characters: about 112 teeth in total (including the upper and
      lower jaws); the dentition occupies more than 50% of the skull length; the
      anterior teeth vary in size; the mandibular symphysis is longer than half of the
      whole mandible length; in ventral view, an apparent symphyseal trough in the
      median part of the symphysis.

PMID- 22146957
TI  - Economic valuation of the Emas waterfall, Mogi-Guacu River, SP, Brazil.
AB  - The Emas waterfall in Mogi-Guacu River is regionally recognized as an important
      fishing spot and touristic place. The first reports of the professional and sport
      fishing there date back from the 30's, which is the same period when the tourism
      took place. The present paper provides an environmental valuation of this place
      and an assessment of the differences among the major groups of people using the
      area. During 2006 we interviewed 33 professional fishers, 107 sport fishers, 45
      tourists and 103 excursionists in order to estimate the Willingness to Pay (WTP)
      for each category and to analyze the influence of socioeconomic factors by means
      of logistic regressions and ANCOVAs. The WTP of professional fisher was
      significantly influenced by age and education, and the WTP for the sport fishers
      was influenced by the family income. The variables that influenced the tourists'
      and excursionists' WTP were sex and education. The total annual aggregated value
      to maintain the waterfall in the current conditions was estimated in US$
      11.432.128, and US$ 55.424.283 to restore it.

PMID- 22146958
TI  - Diet and nematode infection in Proceratoprhys boiei from two Atlantic rainforest
      remnants in Southeastern Brazil.
AB  - Proceratophrys boiei is an endemic cycloramphid anuran inhabiting the leaf litter
      of Atlantic rainforests in Southeastern Brazil. We analyzed the whole digestive
      tract of 38 individuals of Proceratophrys boiei collected in two Atlantic
      Rainforest areas in the state of Rio de Janeiro, Brazil, to study the diet
      composition and the helminth fauna associated with this species. The main food
      items in P. boiei's diet were Coleoptera, Orthoptera and Blattaria. Five nematode
      species were found: Aplectana delirae, Cosmocerca parva, Oxyascaris oxyascaris,
      Physaloptera sp. (larval stage only) and an unidentified nematode. Overall
      prevalence was 71% and mean infection intensity was 7.3 +/- 5.8 neatodes per
      individual.

PMID- 22146959
TI  - Phytoplankton abundance, dominance and coexistence in an eutrophic reservoir in
      the state of Pernambuco, Northeast Brazil.
AB  - The present study reports the phytoplankton abundance, dominance and co-existence
      relationships in the eutrophic Carpina reservoir, Pernambuco, Brazil. Sampling
      was carried out at six different depths bimonthly at a single reservoir spanning
      two climatic periods: dry season (January, September, and November 2006) and
      rainy season (March, May, and July 2006). Density, abundance, dominance, specific
      diversity and equitability of the community were determined, along with
      chlorophyll a, and physical and chemical variables of the environment. Eight
      species were considered abundant, and their densities corresponded to more than
      90% of the total phytoplankton community quantified. Cyanobacteria represented
      more than 80% of this density. Cylindrospermopsis raciborskii was the only
      dominant taxon in the dry season, and was co-dominant in the rainy season. C.
      raciborskii, Planktothrix agardhii and Geitlerinema amphibium had the greatest
      densities and lowest vertical variation coefficients. The statistical analysis
      indicated relationships with vertical and seasonal variations in the
      phytoplankton community and the following variables: total dissolved solids,
      water temperature, electrical conductivity and pH. The changes in the
      environmental variables were discrete and regulated by the establishment of
      precipitation however, they were able to promote vertical and seasonal
      instability in the structure of the phytoplankton community.

PMID- 22146960
TI  - Cyanobacterial blooms in stratified and destratified eutrophic reservoirs in semi
      arid region of Brazil.
AB  - This study investigated the dynamics of cyanobacteria in two deep, eutrophic
      reservoirs in a semi-arid region of Brazil during periods of stratification and
      destratification. Four collections were carried out at each reservoir at two
      depths at three-month intervals. The following abiotic variables were analyzed:
      water temperature, dissolved oxygen, pH, turbidity, water transparency, total
      phosphorus, total dissolved phosphorus, orthophosphate and total nitrogen.
      Phytoplankton density was quantified for the determination of the biomass of
      cyanobacteria. The data were analyzed using CCA. Higher mean phytoplankton
      biomass values (29.8 mm(3).L(-1)) occurred in the period of thermal
      stratification. A greater similarity in the phytoplankton communities also
      occurred in this period and was related to the development of cyanobacteria,
      mainly Cylindrospermopsis raciborskii (>3.9 mm(3).L(-1)). During the period of
      thermal destratification, this species co-dominated the environment with
      Planktothrix agardhii, Geitlerinema amphibium, Microcystis aeruginosa and
      Merismopedia tenuissima, as well as with diatoms and phytoflagellates.
      Environmental instability and competition among algae hindered the establishment
      of blooms more during the mixture period than during the stratification period.
      Thermal changes in the water column caused by climatologic events altered other
      physiochemical conditions of the water, leading to changes in the composition and
      biomass of the cyanobacterial community in tropical reservoirs.

PMID- 22146961
TI  - Caring about medullary anesthesia in Saimiri sciureus: the conus medullaris
      topography.
AB  - Saimiri sciureus is a New World non-human primate (NHP) that inhabits Brazilian
      rain forests. Surgical interventions in wild NHPs can be considered common both
      for experimental studies procedures and corrective procedures for endangered
      species. Among various anesthetic procedures, the epidural anesthesia or
      blockades, depending on the surgical procedure, might be considered elective for
      wild monkeys, mostly based on its safeness, efficiency and non-time consuming
      characteristics. However its safeness would be limiting because of the spinal
      cord arrangement. Notwithstanding the available former studies on New World NHP
      anatomy, the description of the medullar cone of Saimiri sciureus is still
      scarce. Therefore, we believe that the better understanding the medullar cone of
      Saimiri sciureus would contribute to improve the applicability of epidural
      procedures in the species. Vertebrae architecture of Saimiri sciureus was
      composed by 9 lumbar, 3 sacral and 18 coccygeal vertebrae, and the medullar cone
      measured about 3.3 cm. We can conclude that the conus medullaris in Saimiri
      sciureus is situated more caudally in comparison to other species.

PMID- 22146962
TI  - Pampean lizard assemblage from subtropical Brazil: a temporal analysis.
AB  - The increasing human occupation of natural environments is one of the greatest
      threats to biodiversity. To mitigate the negative anthropogenic effects, it is
      necessary to understand the characteristics of natural populations and the
      natural history of species. A study was conducted with an assemblage of lizards
      from a disturbed area of the Pampa biome, from February 2001 to January 2004. The
      assemblage showed a unimodal seasonal pattern, with the recruitment period
      occurring during the warmer months. The captures were seasonal for two of the
      three monitored years, and concentrated within warmer months. The minimum
      temperature explained the number of catches for the assemblage as a whole.
      However, when the species were analyzed individually, the temperature only
      explained the seasonal occurrence of Teius oculatus. The abundance of species was
      significantly different in the third year of study for Cercosaura schreibersii
      and Ophiodes striatus. This latter species was no longer registered in the study
      area from May 2003 until the end of the study. Therefore, O. striatus may be more
      sensitive to environmental changes, considering the events of change in
      vegetation during the study. With frequent and increasing environmental
      disturbances, it is necessary to take conservation measures and encourage the
      increase of knowledge on Pampean lizards.

PMID- 22146963
TI  - Sporothrix schenckii in a hospital and home environment in the city of Pelotas/RS
      - Brazil.
AB  - This study describes the isolation of S. schenckii in hospital and home
      environments in Brazil. Samples were collected from surfaces of a veterinary
      service place and at home. S. schenckii was detected in 1.5% of the samples from
      the hospital environment. However, this fungus was isolated from all sampled
      areas in home environments. The isolation of S. schenckii demonstrates that these
      surfaces could act as infection sources to animals and humans. Therefore,
      employees and pet owners could be exposed to this agent, and the contamination,
      through surfaces, could occur through the traumatic inoculation of the fungus or
      by direct contact with pre-existing lesions.

PMID- 22146964
TI  - Treatment of fear memories: interactions between extinction and reconsolidation.
AB  - Retrieval labilizes memory traces and these gates two protein synthesis-dependent
      processes in the brain: extinction, which inhibits further retrieval, and
      reconsolidation, which may enhance retrieval or change its content. Extinction
      may itself suffer reconsolidation. Interactions among these processes may be
      applied to treatments of fear memories, such as those underlying post-traumatic
      stress disorders.

PMID- 22146965
TI  - Hepatoprotective, cardioprotective, and renal-protective effects of organic and
      conventional grapevine leaf extracts on Wistar rat tissues.
AB  - The purpose of this study was to evaluate the beneficial effects of organic and
      conventional grapevine (Vitis labrusca L.) leaf extracts in reducing hydrogen
      peroxide-induced stress in the liver, heart and kidney of Wistar rats by
      measuring lipids and proteins damages (carbonyl assay), as well as the activity
      of the antioxidant enzymes superoxide dismutase and catalase. The preincubation
      with 5 mg/mL of organic and conventional grapevine (Vitis labrusca L.) leaf
      extracts prevented both lipids and proteins oxidative damages in all tissues
      analyzed. The organic leaf extract was able to restore superoxide dismutase
      (kidney and liver) and catalase (heart) activities, which were modified by the
      treatment with H(2)O(2). The conventional extract was able to restore only the
      catalase activity in liver and heart tissues. The beneficial effects of the V
      labrusca leaf extract shown in this study could probably be important for
      formulating dietary supplements, as well as for developing new ingredients with
      improved antioxidant properties from other plant sources.

PMID- 22146966
TI  - Chemical and agronomic development of Kalanchoe brasiliensis Camb. and Kalanchoe
      pinnata Pers under light and temperature levels.
AB  - This study compares the development of Kalanchoe brasiliensis and Kalanchoe
      pinnata, which are medicinal species known as "saiao" and "folha da fortuna" that
      are used interchangeably by the population for medicinal purposes. The experiment
      consisted of 20 plots/species planted in plastic bags with homogeneous substrate
      in a randomized design, which grown under light levels (25%, 50%, 70%, full
      sunlight) at environment temperature, and a treatment under a plastic with
      greater temperature range than the external environment. It was obtained for K.
      pinnata a greater plant height, total length of sprouts, stems, production and
      dry matter content of leaves than that obtained for K. brasiliensis, which
      achieved higher averages only for the length of lateral branches. The species
      showed increases in height, which varied in inverse proportion to the light, and
      it was observed the influence of temperature in K. pinnata. The production and
      dry matter content of leaves were proportional to the luminosity; the same
      occurred in the thickness of leaves for K. brasiliensis. In the swelling index
      and Brix degree, K. brasiliensis showed higher averages than K. pinnata. In
      relation to the total content of flavonoids it was not observed significant
      differences for both species. The analyzed parameters showed the main differences
      in the agronomic development of the two species.

PMID- 22146967
TI  - Contiguous urban rivers should not be necessarily submitted to the same
      management plan: the case of Tiete and Pinheiros Rivers (Sao Paulo-Brazil).
AB  - The management of urban water resources plays an important role for developing
      countries. The Tiete and Pinheiros Rivers (Sao Paulo, Brazil) are affected by
      domestic and industrial effluents and by the diffuse pollution. This research
      aimed to quantify 134 variables in the water of Tiete and Pinheiros Rivers
      (approximately 7,200 and 6,600 analyses, respectively) from August 2007 to
      December 2008. The idea was to verify if the fact that both rivers are located in
      the same basin is enough to consider the application of a single management plan
      for both. Data showed that the rivers presented significant anthropogenic
      interference. The results suggested that such rivers must be subjected to
      individual management plans since there were exclusive occurrences (variables
      that were only detected in one of the rivers). Moreover, there was a
      statistically significant difference between rainy and dry periods for eleven
      variables (p*<0.05, ANOVA), reinforcing the special importance of the temporal
      component within the monitoring program. It is expected that this study subsidize
      environmental recovery programs in the Tiete River, to which is recommendable to
      focus on prosecution of illegal wastewater releases, and in the Pinheiros River,
      to which special attention is suggested to the pollution derived from the
      pesticides load to the water body.

PMID- 22146968
TI  - Long-term bonding to eroded dentin requires superficial bur preparation.
AB  - OBJECTIVES: This study aims to evaluate the influence of different surface
      preparation techniques on long-term bonding effectiveness to eroded dentin.
      MATERIALS AND METHODS: Dentin specimens were eroded by pH cycling or were left
      untreated as control, respectively. Five different "preparation" techniques were
      applied: (1) cleaning with pumice, (2) air abrasion, (3) silicon polisher, (4)
      proxo-shape, and (5) diamond bur. The three-step etch-and-rinse adhesive OptiBond
      FL (O-FL; Kerr) and the mild two-step self-etch adhesive Clearfil SE Bond (C-SE;
      Kuraray) were evaluated. Micro-tensile bond strength was measured after water
      storage for 24 h and 1 year. Fracture analysis was performed by stereomicroscopy
      and SEM. Interfaces were characterized by TEM. Differences were statistically
      analyzed with a linear mixed effects model (alpha = 0.05). RESULTS: Erosion
      reduced bond strength in all groups, but this effect was less prominent when
      eroded dentin was prepared by diamond bur. Storage lowered bond strength in
      almost all groups significantly, but this ageing effect was more prominent for
      the eroded surfaces than for non-eroded controls. Whereas after 1-year control
      specimens revealed superior bond strength with the three-step etch-and-rinse
      adhesive (O-FL), the mild two-step self-etch adhesive (C-SE) revealed a better 1
      year bond strength to eroded dentin. The interface at eroded dentin appeared very
      prone to degradation as was shown by the increased amount of adhesive failures
      and by the silver infiltration detected by TEM. CONCLUSIONS AND CLINICAL
      RELEVANCE: Although a minimally invasive approach should clinically always be
      strived for, superficial preparation (or minimal roughening) with a diamond bur
      is recommendable for long-term bonding to eroded dentin.

PMID- 22146969
TI  - Druggability of methyl-lysine binding sites.
AB  - Structural modules that specifically recognize--or read--methylated or acetylated
      lysine residues on histone peptides are important components of chromatin
      mediated signaling and epigenetic regulation of gene expression. Deregulation of
      epigenetic mechanisms is associated with disease conditions, and antagonists of
      acetyl-lysine binding bromodomains are efficacious in animal models of cancer and
      inflammation, but little is known regarding the druggability of methyl-lysine
      binding modules. We conducted a systematic structural analysis of readers of
      methyl marks and derived a predictive druggability landscape of methyl-lysine
      binding modules. We show that these target classes are generally less druggable
      than bromodomains, but that some proteins stand as notable exceptions.

PMID- 22146970
TI  - Morphogenesis of Pseudopallene sp. (Pycnogonida, Callipallenidae) II:
      postembryonic development.
AB  - Pycnogonida (sea spiders) are bizarre marine arthropods that are nowadays most
      frequently considered as being the sister group to all other chelicerates. The
      majority of pycnogonid species develops via a protonymphon larva with only three
      pairs of limbs affiliated with the future head region. Deviating from this, the
      hatching stage of some representatives shows already an advanced degree of trunk
      differentiation. Using scanning electron microscopy, fluorescent nucleic
      staining, and bright-field stereomicroscopy, postembryonic development of
      Pseudopallene sp. (Callipallenidae), a pycnogonid with an advanced hatching
      stage, is described. Based on external morphology, six postembryonic stages plus
      a sub-adult stage are distinguished. The hatching larva is lecithotrophic and
      bears the chelifores as only functional appendage pair and unarticulated limb
      buds of walking leg pairs 1 and 2. Palpal and ovigeral larval limbs are absent.
      Differentiation of walking leg pairs 3 and 4 is sequential. Apart from the first
      pair, each walking leg goes through a characteristic sequence of three externally
      distinct stages with two intermittent molts (limb bud-seven podomeres-nine
      podomeres). First external signs of oviger development are detectable in
      postembryonic stage 3 bearing three articulated walking leg pairs. Following
      three more molts, the oviger has attained adult podomere composition. The
      advanced hatching stages of different callipallenids are compared and the
      inclusive term "walking leg-bearing larva" is suggested, as opposed to the
      behavior-based name "attaching larva". Data on temporal and structural patterns
      of walking leg differentiation in other pycnogonids are reviewed and discussed.
      To facilitate comparisons of walking leg differentiation patterns across many
      species, we propose a concise notation in matrix fashion. Due to deviating
      structural patterns of oviger differentiation in another callipallenid species as
      well as within other pycnogonid taxa, evolutionary conservation of characteristic
      stages of oviger development is not apparent even in closely related species.

PMID- 22146972
TI  - Medicinal plants of Thailand. II: chemical studies on the seed kernels of Entada
      rheedei Sprengel.
AB  - Chemical investigation of a methanolic extract of the seed kernels of Entada
      rheedei (Fabaceae), a Thai medicinal plant taken for stomachache, led to the
      isolation of five new compounds, 1-(3,4-dimethoxyphenyl)propan-9-ol O-(6"-O-alpha
      L-arabinopyranosyl)-beta-D-glucopyranoside, 1-(3,4,5-trimethoxyphenyl)prop-7-en-9
      ol O-(6"-O-alpha-L-arabinopyranosyl)-beta-D-glucopyranoside, and N-(2'
      hydroxyethyl)-7-phenylacetamide 2'-O-beta-D-glucopyranoside, and entadamide A 2'
      O-(4"-O-beta-D-glucopyranosyl)-beta-D-glucopyranoside and 2'-O-(6"-O-beta-D
      glucopyranosyl)-beta-D-glucopyranosides, together with one known compound,
      corchoionoside C. Their structures were elucidated on the basis of chemical and
      spectral evidence.

PMID- 22146971
TI  - Phytochemical characterization and antinociceptive effect of Lippia gracilis
      Schauer.
AB  - Lippia gracilis Schauer is an aromatic plant widely found in Northeastern Brazil.
      The leaf infusions or decoctions and alcoholic macerate are used for some
      inflammatory diseases and headache. This paper reports the isolation of
      naringenin by semi-preparative liquid chromatography from the methanolic extract
      of L. gracilis (ELg) and the evaluation of the analgesic and anti-inflammatory
      activities of this extract by measuring nociception through acetic acid,
      formalin, and hot-plate tests in carrageenan-induced inflammation in mice.
      Following oral administration, ELg (100, 200, and 400 mg/kg) significantly
      reduced the number of writhes in the writhing test and the time of paw licks in
      both phases of the formalin test when compared to the control group animals. Mice
      treated with ELg did not exhibit any behavioral alteration during the hot plate
      and rota-rod tests, suggesting non-participation of the supraspinal components in
      the modulation of pain by ELg and no motor abnormality. The oral administration
      of 400 mg/kg of ELg produced an anti-inflammatory effect on peritonitis induced
      by carrageenan. These effects can be associated with a decrease of inflammatory
      mediator synthesis by compounds of ELg, such as naringenin, which has anti
      inflammatory action as already described.

PMID- 22146973
TI  - Pulmonary masses: initial results of cone-beam CT guidance with needle planning
      software for percutaneous lung biopsy.
AB  - PURPOSE: To evaluate the outcome of percutaneous lung biopsy (PLB) findings using
      cone-beam computed tomographic (CT) guidance (CBCT guidance) and compared to
      conventional biopsy guidance techniques. METHODS: CBCT guidance is a stereotactic
      technique for needle interventions, combining 3D soft-tissue cone-beam CT, needle
      planning software, and real-time fluoroscopy. Between March 2007 and August 2010,
      we performed 84 Tru-Cut PLBs, where bronchoscopy did not provide histopathologic
      diagnosis. Mean patient age was 64.6 (range 24-85) years; 57 patients were men,
      and 25 were women. Records were prospectively collected for calculating
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy. We also registered fluoroscopy time, room time, interventional
      time, dose-area product (DAP), and complications. Procedures were divided into
      subgroups (e.g., location, size, operator). RESULTS: Mean lesion diameter was
      32.5 (range 3.0-93.0) mm, and the mean number of samples per biopsy procedure was
      3.2 (range 1-7). Mean fluoroscopy time was 161 (range 104-551) s, room time was
      34 (range 15-79) min, mean DAP value was 25.9 (range 3.9-80.5) Gy.cm(-2), and
      interventional time was 18 (range 5-65) min. Of 84 lesions, 70 were malignant
      (83.3%) and 14 were benign (16.7%). Seven (8.3%) of the biopsy samples were
      nondiagnostic. All nondiagnostic biopsied lesions proved to be malignant during
      surgical resection. The outcome for sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy was 90% (95% confidence interval
      [CI] 86-96), 100% (95% CI 82-100), 100% (95% CI 96-100), 66.7% (95% CI 55-83),
      and 91.7% (95% CI 86-96), respectively. Sixteen patients (19%) had minor and 2
      (2.4%) had major complications. CONCLUSION: CBCT guidance is an effective method
      for PLB, with results comparable to CT/CT fluoroscopy guidance.

PMID- 22146975
TI  - Endovascular treatment of malignant superior vena cava syndrome: results and
      predictive factors of clinical efficacy.
AB  - PURPOSE: To demonstrate the effectiveness of endovascular treatment (EVT) with
      self-expandable bare stents for malignant superior vena cava syndrome (SVCS) and
      to analyze predictive factors of EVT efficacy. METHODS: Retrospective review of
      the 164 patients with malignant SVCS treated with EVT in our hospital from August
      1992 to December 2007 and followed until February 2009. Endovascular treatment
      includes angioplasty before and after stent placement. We used self-expandable
      bare stents. We studied results of this treatment and looked for predictive
      factors of clinical efficacy, recurrence, and complications by statistical
      analysis. RESULTS: Endovascular treatment was clinically successful in 95% of
      cases, with an acceptable rate of early mortality (2.4%). Thrombosis of the
      superior vena cava was the only independent factor for EVT failure. The use of
      stents over 16 mm in diameter was a predictive factor for complications (P =
      0.008). Twenty-one complications (12.8%) occurred during the follow-up period.
      Relapse occurred in 36 patients (21.9%), with effective restenting in 75% of
      cases. Recurrence of SVCS was significantly increased in cases of occlusion (P =
      0.01), initial associated thrombosis (P = 0.006), or use of steel stents (P =
      0.004). Long-term anticoagulant therapy did not influence the risk of recurrence
      or complications. CONCLUSION: In malignancy, EVT with self-expandable bare stents
      is an effective SVCS therapy. These results prompt us to propose treatment with
      stents earlier in the clinical course of patients with SVCS and to avoid
      dilatation greater than 16 mm.

PMID- 22146976
TI  - Endovascular treatment of visceral aneurysms and pseudoaneurysms: long-term
      outcomes from a multicenter European study.
AB  - PURPOSE: To investigate the percutaneous endovascular management of visceral
      aneurysms (VA) and visceral pseudoaneurysms (VPA) treated in three European
      interventional radiology departments. METHODS: Patient archives from the
      department's databases were examined and retrospectively analyzed. Patients
      diagnosed between 2000 and 2010 with VA and/or VPA, confirmed by computed
      tomography angiography, magnetic resonance angiography, or digital subtraction
      angiography and treated exclusively with percutaneous endovascular methods, were
      included in the study. The study's primary end points were procedural technical
      success, target lesion reintervention rate, and periprocedural mortality rate.
      Secondary end points included major and minor complications rates. RESULTS: The
      medical records of 54 patients (41 male, mean age 55 +/- 18.1 years) with 58 VAs
      or VPAs and treated with various percutaneous endovascular therapeutic modalities
      were analyzed. In total, 21 VAs (mean diameter 49.4 +/- 21 mm, range 20-100 mm)
      and 37 VPAs (mean diameter 25.1 +/- 14.6 mm, range 8-60 mm) were treated.
      Procedural technical success was achieved in 100% of the cases, while target
      lesion reintervention rate was 6.1% (2 of 33) and 14.2% (3 of 21) in the VPA and
      VA groups, respectively. Mean clinical follow-up period was 19.1 +/- 21.4 months.
      Overall periprocedural mortality rate was 3% (1 of 33) in the VPA group and 0% (0
      of 21) in the VA group. CONCLUSION: Percutaneous endovascular treatment of VAs
      and VPAs is safe and effective with low morbidity and mortality. There is a small
      but significant reintervention rate, particularly for true aneurysms; dedicated
      follow-up imaging is recommended. Successful aneurysm exclusion was achieved in
      all cases with a second procedure.

PMID- 22146977
TI  - Targeted vessel ablation for more efficient magnetic resonance-guided high
      intensity focused ultrasound ablation of uterine fibroids.
AB  - PURPOSE: To report the first clinical experience with targeted vessel ablation
      during magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU)
      treatment of symptomatic uterine fibroids. METHODS: Pretreatment T1-weighted
      contrast-enhanced magnetic resonance angiography was used to create a detailed
      map of the uterine arteries and feeding branches to the fibroids. A three
      dimensional overlay of the magnetic resonance angiography images was registered
      on 3D T2-weighted pretreatment imaging data. Treatment was focused primarily on
      locations where supplying vessels entered the fibroid. Patients were followed 6
      months after treatment with a questionnaire to assess symptoms and quality of
      life (Uterine Fibroid Symptom and Quality of Life) and magnetic resonance imaging
      to quantify shrinkage of fibroid volumes. RESULTS: In two patients, three
      fibroids were treated with targeted vessel ablation during MR-HIFU. The
      treatments resulted in almost total fibroid devascularization with nonperfused
      volume to total fibroid volume ratios of 84, 68, and 86%, respectively, of
      treated fibroids. The predicted ablated volumes during MR-HIFU in patients 1 and
      2 were 45, 40, and 82 ml, respectively, while the nonperfused volumes determined
      immediately after treatment were 195, 92, and 190 ml respectively, which is 4.3
      (patient 1) and 2.3 (patient 2) times higher than expected based on the thermal
      dose distribution. Fibroid-related symptoms reduced after treatment, and quality
      of life improved. Fibroid volume reduction ranged 31-59% at 6 months after
      treatment. CONCLUSION: Targeted vessel ablation during MR-HIFU allowed nearly
      complete fibroid ablation in both patients. This technique may enhance the use of
      MR-HIFU for fibroid treatment in clinical practice.

PMID- 22146978
TI  - Optically induced microfluidic reconfiguration.
AB  - Reconfigurable systems, like the field-programmable gate array in electronics,
      have numerous advantages including cost, adaptability, robustness, and security.
      Despite this, few other chip-based technologies have developed equivalently
      ubiquitous reconfiguration methods. As a first step to applying this paradigm to
      channel-based microfluidics, we present here a rapid optofluidic technique to
      create, move, and remove arbitrary solid regions in a microfluidic flow simply by
      illumination with an optical pattern. While other techniques have shown the
      ability to manipulate individual particles using spatial light modulation, we
      demonstrate here the ability to create reconfigurable flow pathways and build
      morphable channel structures. These structures can be modified on the order of
      seconds using a combined photothermal and thermo-rheological effect. In addition
      to characterizing the effect, we also apply this technique to create dynamic
      traps for biomolecules, and demonstrate trapping of lambda-DNA molecules and
      nanoparticles, with a 25 fold suppression of diffusion.

PMID- 22146979
TI  - Roles of genetic variants in the PI3K and RAS/RAF pathways in susceptibility to
      endometrial cancer and clinical outcomes.
AB  - PURPOSE: The phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mTOR and
      Ras/Raf/MEK/ERK pathways have been implicated in endometrial tumorigenesis. In
      this candidate pathway analysis, we investigated associations between genetic
      variations in these two pathways and both risk and clinical outcomes of
      endometrial cancer. METHODS: We genotyped a total of 48 potentially functional
      SNPs in 11 key genes (AKT1, AKT2, AKT3, BRAF, FRAP1, KRAS, PDPK1, PIK3CA, PIK3CB,
      PIK3R1, and PTEN) with the Sequenom genotyping platform in 115 endometrial cancer
      patients and 230 cancer-free women to evaluate their associations with risk,
      survival, and recurrence of endometrial cancer. RESULTS: We found the following:
      (1) PIK3CA rs6443624 and rs9838411 variants either borderline or significantly
      decreased risk of endometrial cancer in a dominant model (adjusted odds ratio
      [OR], 0.62; 95% CI, 0.39-1.00 and 0.59; 95% CI, 0.36-0.95, respectively).
      Furthermore, there was a statistically significant multiplicative interaction (P
      (int) = 0.036) between these two loci in risk of endometrial cancer. In contrast,
      the AKT1 rs2498801 genotype significantly increased risk of endometrial cancer
      (adjusted OR, 1.94; 95% CI, 1.02-3.67 in a recessive model). (2) In Cox
      regression analyses, three SNPs (PIK3R1 rs1862162, AKT2 rs892119, and PIK3CA
      rs2699887) showed significant associations with survival of endometrial cancer
      patients. (3) KRAS rs7312175 and PIK3CA rs6443624 had significant effects on
      recurrence of endometrial cancer individually and combined in a locus-dosage
      manner (adjusted P (trend) = 0.003). CONCLUSION: These results suggest that
      common genetic variations in these pathways may modulate risk and clinical
      outcomes of endometrial cancer. Further replication and functional studies are
      needed to confirm these findings.

PMID- 22146980
TI  - Population divergence with or without admixture: selecting models using an ABC
      approach.
AB  - Genetic data have been widely used to reconstruct the demographic history of
      populations, including the estimation of migration rates, divergence times and
      relative admixture contribution from different populations. Recently, increasing
      interest has been given to the ability of genetic data to distinguish alternative
      models. One of the issues that has plagued this kind of inference is that
      ancestral shared polymorphism is often difficult to separate from admixture or
      gene flow. Here, we applied an approximate Bayesian computation (ABC) approach to
      select the model that best fits microsatellite data among alternative splitting
      and admixture models. We performed a simulation study and showed that with
      reasonably large data sets (20 loci) it is possible to identify with a high level
      of accuracy the model that generated the data. This suggests that it is possible
      to distinguish genetic patterns due to past admixture events from those due to
      shared polymorphism (population split without admixture). We then apply this
      approach to microsatellite data from an endangered and endemic Iberian freshwater
      fish species, in which a clustering analysis suggested that one of the
      populations could be admixed. In contrast, our results suggest that the observed
      genetic patterns are better explained by a population split model without
      admixture.

PMID- 22146981
TI  - Copy number polymorphism in the alpha-globin gene cluster of European rabbit
      (Oryctolagus cuniculus).
AB  - Comparative genomic studies have revealed that mammals typically possess two or
      more tandemly duplicated copies of the alpha-globin (HBA) gene. The domestic
      rabbit represents an exception to this general rule, as this species was found to
      possess a single HBA gene. Previous electrophoretic surveys of HBA polymorphism
      in natural populations of the European rabbit (Oryctolagus cuniculus) revealed
      extensive geographic variation in the frequencies of three main electromorphs.
      The variation in frequency of two electromorphs is mainly partitioned between two
      distinct subspecies of European rabbit, and a third is restricted to the hybrid
      zone between the two rabbit subspecies in Iberia. Here we report the results of a
      survey of nucleotide polymorphism, which revealed HBA copy number polymorphism in
      Iberian populations of the European rabbit. By characterizing patterns of HBA
      polymorphism in populations from the native range of the European rabbit, we were
      able to identify the specific amino-acid substitutions that distinguish the
      previously characterized electromorphs. Within the hybrid zone, we observed the
      existence of a second HBA gene duplicate, named HBA2, that mostly represents a
      novel sequence haplotype, which occurs in higher frequency within the hybrid
      zone, and thus appears to have arisen in hybrids of the two distinct subspecies.
      Although this novel gene is also present in other wild Iberian populations, it is
      almost absent from French populations, which suggest a recent ancestry,
      associated with the establishment of the post-Pleistocene contact zone between
      the two European rabbit subspecies.

PMID- 22146982
TI  - Anatomy of the retrohepatic segment of the inferior vena cava and the ostia venae
      hepaticae with its clinical significance.
AB  - PURPOSE: The present study was undertaken to provide morphological data regarding
      the retrohepatic segment of the inferior vena cava (RHIVC) and ostia venae
      hepaticae with an emphasis on the clinical significance of the observations made.
      METHODS: This was an observational study conducted on 160 apparently healthy,
      randomly selected, cadaveric adult human livers fixed in 10% formalin. The
      distribution of the hepatic venous openings was studied by dividing the interior
      of the RHIVC into 16 quadrants. These openings were classified as large, medium,
      small and very small openings based on their diameter and were also classified as
      single/double/triple/quadruple according to the number of veins opening into
      them. RESULTS: The median length of RHIVC was 7.3 cm (6.2-8.4) and was directed
      obliquely with respect to the vertical axis of the liver in 92.5% of cases. A
      total of 1,376 ostia venae hepaticae were observed, and the median number of
      openings per liver was 7 (5-9). The right hepatic vein had a single opening in
      156 (97.5%) and the left and middle hepatic veins had a common opening in 144
      (90%) cases. A longitudinal area on the anterior wall of the RHIVC, to the right
      side of the midline, was relatively avascular with 10.1% of the venous openings,
      of which 70% were single openings of the right dorsal vein having a small
      diameter (0.1-0.5 cm). CONCLUSION: During liver hanging maneuver, rightward
      direction of the dissecting forceps would avoid injury to the caudate vein and
      allow access to the safe avascular space in the RHIVC.

PMID- 22146983
TI  - High-pressure phase transition and thermoelastic properties of europium
      chalcogenides.
AB  - The pressure-induced crystal properties of Eu chalcogenides were investigated
      using two different models: a modified charge-transfer potential model consisting
      of Coulomb screening due to the delocalization of the f electron of the rare
      earth atom, and modified by covalency and zero-point energy effects along with
      attractive and repulsive interactions; and a charge-transfer model that excluded
      the covalency and zero-point energy effects in the previous model. Both models
      were used to visualize the effect of covalency on the mechanism of interaction of
      the constituent atoms. Eu chalcogenides transform from the Fm3m to the Pm3m phase
      under the influence of sufficient pressure (P(T) = 39.52, 21.01, 14.31, and 10.58
      GPa), and their equations of state indicated decreases in volume during this
      phase transition of 6.38, 12.32, 12.76, and 11.15%, respectively, for EuO, EuS,
      EuSe, and EuTe. The results obtained from the models were in good agreement with
      corresponding experimental data. The elastic constants and Debye temperatures
      were also computed at normal and high pressures. Both of the models were found to
      be capable of successfully explaining these properties.

PMID- 22146984
TI  - Structural, electronic and magnetic effects of Al-doped niobium clusters: a
      density functional theory study.
AB  - The application of the ab initio stochastic search procedure with Saunders "kick"
      method has been carried out for the elucidation of global minimum structures of a
      series of Al-doped clusters, Nb(n)Al (1 <= n <= 10). We have studied the
      structural characters, growth behaviors, electronic and magnetic properties of
      Nb(n)Al by the density functional theory calculations. Unlike the previous
      literature reported on Al-doped systems where ground state structures undergo a
      structural transition from the Al-capped frame to Al-encapsulated structure, we
      found that Al atom always occupies the surface of Nb(n)Al clusters and structural
      transition does not take place until n = 10. Note that the fragmentation proceeds
      preferably by the ejection of an aluminum atom other than niobium atom. According
      to the natural population analysis, charges always transfer from aluminum to
      niobium atoms. Furthermore, the magnetic moments of the Nb(n)Al clusters are
      mainly located on the 4d orbital of niobium atoms, and aluminum atom possesses
      very small magnetic moments.

PMID- 22146985
TI  - Structure prediction and binding sites analysis of curcin protein of Jatropha
      curcas using computational approaches.
AB  - Ribosome inactivating proteins (RIPs) are defense proteins in a number of higher
      plant species that are directly targeted toward herbivores. Jatropha curcas is
      one of the biodiesel plants having RIPs. The Jatropha seed meal, after extraction
      of oil, is rich in curcin, a highly toxic RIP similar to ricin, which makes it
      unsuitable for animal feed. Although the toxicity of curcin is well documented in
      the literature, the detailed toxic properties and the 3D structure of curcin has
      not been determined by X-ray crystallography, NMR spectroscopy or any in silico
      techniques to date. In this pursuit, the structure of curcin was modeled by a
      composite approach of 3D structure prediction using threading and ab initio
      modeling. Assessment of model quality was assessed by methods which include
      Ramachandran plot analysis and Qmean score estimation. Further, we applied the
      protein-ligand docking approach to identify the r-RNA binding residue of curcin.
      The present work provides the first structural insight into the binding mode of r
      RNA adenine to the curcin protein and forms the basis for designing future
      inhibitors of curcin. Cloning of a future peptide inhibitor within J. curcas can
      produce non-toxic varieties of J. curcas, which would make the seed-cake suitable
      as animal feed without curcin detoxification.

PMID- 22146986
TI  - Introgression and pyramiding into common bean market class fabada of genes
      conferring resistance to anthracnose and potyvirus.
AB  - Anthracnose and bean common mosaic (BCM) are considered major diseases in common
      bean crop causing severe yield losses worldwide. This work describes the
      introgression and pyramiding of genes conferring genetic resistance to BCM and
      anthracnose local races into line A25, a bean genotype classified as market class
      fabada. Resistant plants were selected using resistance tests or combining
      resistance tests and marker-assisted selection. Lines A252, A321, A493, Sanilac
      BC6-Are, and BRB130 were used as resistance sources. Resistance genes to
      anthracnose (Co-2 ( C ), Co-2 ( A252 ) and Co-3/9) and/or BCM (I and bc-3) were
      introgressed in line A25 through six parallel backcrossing programs, and six
      breeding lines showing a fabada seed phenotype were obtained after six backcross
      generations: line A1258 from A252; A1231 from A321; A1220 from A493; A1183 and
      A1878 from Sanilac BC6-Are; and line A2418 from BRB130. Pyramiding of different
      genes were developed using the pedigree method from a single cross between lines
      obtained in the introgression step: line A1699 (derived from cross A1258 *
      A1220), A2438 (A1220 * A1183), A2806 (A1878 * A2418), and A3308 (A1699 * A2806).
      A characterization based on eight morpho-agronomic traits revealed a limited
      differentiation among the obtained breeding lines and the recurrent line A25.
      However, using a set of seven molecular markers linked to the loci used in the
      breeding programs it was possible to differentiate the 11 fabada lines.
      Considering the genetic control of the resistance in resistant donor lines, the
      observed segregations in the last backcrossing generation, the reaction against
      the pathogens, and the expression of the molecular markers it was also possible
      to infer the genotype conferring resistance in the ten fabada breeding lines
      obtained. As a result of these breeding programs, genetic resistance to three
      anthracnose races controlled by genes included in clusters Co-2 and Co-3/9, and
      genetic resistance to BCM controlled by genotype I + bc-3 was combined in the
      fabada line A3308.

PMID- 22146987
TI  - Detecting specific genotype by environment interactions using marginal maximum
      likelihood estimation in the classical twin design.
AB  - Considerable effort has been devoted to the analysis of genotype by environment
      (G * E) interactions in various phenotypic domains, such as cognitive abilities
      and personality. In many studies, environmental variables were observed
      (measured) variables. In case of an unmeasured environment, van der Sluis et al.
      (2006) proposed to study heteroscedasticity in the factor model using only MZ
      twin data. This method is closely related to the Jinks and Fulker (1970) test for
      G * E, but slightly more powerful. In this paper, we identify four challenges to
      the investigation of G * E in general, and specifically to the heteroscedasticity
      approaches of Jinks and Fulker and van der Sluis et al. We propose extensions of
      these approaches purported to solve these problems. These extensions comprise:
      (1) including DZ twin data, (2) modeling both A * E and A * C interactions; and
      (3) extending the univariate approach to a multivariate approach. By means of
      simulations, we study the power of the univariate method to detect the different
      G * E interactions in varying situations. In addition, we study how well we could
      distinguish between A * E, A * C, and C * E. We apply a multivariate version of
      the extended model to an empirical data set on cognitive abilities.

PMID- 22146988
TI  - Echocardiographic predictors of ventricular remodeling after acute myocardial
      infarction in rats.
AB  - BACKGROUND: The prediction of the ventricular remodeling process after acute
      myocardial infarction (AMI) may have important clinical implications. OBJECTIVE:
      To analyze echocardiographic variables predictors of remodeling in the infarction
      model in rats. MEHTODS: The animals underwent echocardiography in two moments,
      five days and three months after infarction (AMI group) or sham surgery (control
      group). Linear regression was used to identify the echocardiographic variables on
      the fifth day after the infarction, which were predictive of remodeling after
      three months of coronary occlusion. We considered as a criterion of remodeling in
      this study, the values of left ventricular diastolic diameter (LVDD) after three
      months of infarction. RESULTS: The infarction induced increase in the left
      chambers, associated with changes in systolic and diastolic functions. The
      variables body weight, left ventricular wall stress index (LVWSI), systolic area
      (SA), diastolic area (DA), LVDD, left ventricular systolic diameter (LVSD), area
      variation fraction (AVF), ejection fraction (EF), percent of endocardial
      shortening (%Short), posterior wall shortening velocity (PWSV) and infarct size
      assessed five days after infarction were predictors of LVDD after three months.
      At the multivariate regression analysis, we included the size of infarction, the
      LVWSI and PWSV. The LVWSI (coefficient: 4.402, standard error: 2.221, p = 0.05),
      but not the size of infarction and PWSV, was a predictor of remodeling after
      three months of infarction. CONCLUSION: LVPSI was an independent predictor of
      remodeling three months after the myocardial infarction and could be included in
      the clinical stratification after the coronary occlusion.

PMID- 22146989
TI  - Gender distribution of serum uric acid and cardiovascular risk factors:
      population based study.
AB  - BACKGROUND: There is no data concerning the epidemiology of hyperuricemia in
      Brazilian population-based studies. OBJECTIVE: To investigate the distribution of
      serum uric acid and its relationship with demographics and cardiovascular
      variables. METHODS: We studied 1,346 individuals. Hyperuricemia was defined as >=
      6.8 and >= 5.4 mg/dL for men and women, respectively. Metabolic syndrome (MS) was
      defined with NCEP ATP III criteria. RESULTS: The prevalence of hyperuricemia was
      13.2%. The association of serum uric acid (SUA) with cardiovascular risk factors
      was gender-specific: in women, higher SUA was associated with increasing BMI,
      even after adjustments for age-systolic blood pressure (SBP). In men, the
      relationship of SUA with HDLc was mediated by BMI, whereas in women, SUA was
      similar and dependent on BMI, regardless of glucose levels and presence of
      hypertension. In men, triglycerides, waist circumference (WC) and SBP explained
      11%, 4% and 1% of SUA variability, respectively. In women, WC and triglycerides
      explained 9% and 1% of SUA variability, respectively. Compared to the first
      quartile, men and women in the fourth quartile had a 3.29 fold and 4.18 fold
      increase of MS risk, respectively. Women had almost three fold higher prevalence
      of diabetes mellitus. Normotensive men with MS presented higher SUA, regardless
      of BMI. CONCLUSION: Our results seem to justify the need for gender-based
      evaluation regarding the association of SUA with cardiovascular risk factors,
      which was more pronounced in women. MS was positively associated with increasing
      SUA, regardless of gender. Abdominal obesity and hypertriglyceridemia were the
      main factors associated with hyperuricemia even in normotensive individuals,
      which may add a higher risk for hypertension.

PMID- 22146990
TI  - Mild stunting is associated with higher blood pressure in overweight adolescents.
AB  - BACKGROUND: Studies have shown that pre/postnatal undernutrition leads to higher
      risk of non communicable diseases such as diabetes, hypertension and obesity in
      adulthood. OBJECTIVE: To determine whether overweight adolescents with mild
      stunting [height-for-age Z scores (HAZ) in the range <-1 to >= -2] have higher
      blood pressure than overweight individuals with normal stature (HAZ >= -1).
      METHODS: Participants were classified as mildly stunted or of normal stature, and
      further stratified according to body mass index-for-age percentiles as
      overweight, normal or underweight. Systolic (SBP) and diastolic (DPB) blood
      pressures were determined according to guidelines, and abdominal fat was analyzed
      by dual energy X-ray absorptiometry. RESULTS: Mild stunted overweight individuals
      showed higher DBP values (p=0.001) than their underweight counterparts (69.75 +/-
      12.03 and 54.46 +/- 11.24 mmHg, respectively), but similar to those of normal
      BMI. No differences were found in DBP values of normal, overweight and
      underweight individuals among the normal stature groups. An increase in SBP
      (p=0.01) among mild stunted individuals was found when those with overweight were
      compared to their underweight and normal BMI counterparts (114.70 +/- 15.46,
      97.38 +/- 10.87 and 104.72 +/- 12.24 mmHg, respectively). Although no differences
      were observed in the means of SBP between mild stunting and normal stature
      groups, a significant intercept was found (p=0.01), revealing higher SBP among
      stunted individuals. There was a correlation between SBP and abdominal fat
      (r=0.42, rho=0.02) in the stunted group. CONCLUSION: Stunted individuals with
      overweight showed higher SBP than those of normal stature and overweight. These
      findings confirm that mild stunting increase the risk of future hypertension and
      alterations are evident at early age.

PMID- 22146991
TI  - Contact dermatitis due to dipentene and pine oil in an automobile mechanic.

PMID- 22146992
TI  - Oesophageal carcinoma in a married couple following long-term exposure to dry
      cleaning agents.

PMID- 22146993
TI  - Morphological features of the nasal blood fluke Trichobilharzia regenti
      (Schistosomatidae, Digenea) from naturally infected hosts.
AB  - The first author detected the nasal bird schistosome Trichobilharzia regenti in
      Iceland in Anas platyrhynchos in Landmannalaugar in autumn of 2003. Since then,
      measurements and morphological studies have been performed on fresh worms
      (fragments) obtained in the area from naturally infected ducks, A. platyrhynchos
      and Aythya marila. In the present study, we compare our findings to the original
      description of T. regenti by Horak et al. (Parasite 5:349-357, 1998) that relies
      upon worms obtained by experimental infections of A. platyrhynchos f. domestica
      and Cairina moschata f. domestica ducklings. Fragments obtained from naturally
      infected birds are markedly larger than those obtained in the experimental
      infection. Also, indistinct sex-related size difference was confirmed; males were
      more abundant in the material than females. Previously unknown morphological
      features detected in the present study include, e.g. subterminal spines on the
      oral sucker directed to the oral opening, spine pattern on the apical part of
      acetabulum and long tegumental spines (up to 16 MUm) in the gonad and tail
      regions of both sexes. In males, we evaluated for the first time the morphology
      of the cirrus sac enclosing ejaculatory duct, prostata and the entire prostatic
      region, the course of vas deferens and the position of genital papilla. In
      females, the posterior part of the reproductive system was studied for the first
      time. The presence of the Laurer's canal was confirmed and its course from the
      oviduct to the surface, where spermatozoa were noticed to leave the canal, was
      described.

PMID- 22146994
TI  - In vitro amoebicidal activity of ethanol extracts of Arachis hypogaea L., Curcuma
      longa L. and Pancratium maritimum L. on Acanthamoeba castellanii cysts.
AB  - Acanthamoeba castellanii causes amoebic keratitis which is a painful sight
      threatening disease of the eyes. Its eradication is difficult because the amoebas
      encyst making it highly resistant to anti-amoebic drugs, but several medicinal
      plants have proven to be more effective than the usual therapy. This study aimed
      to evaluate the in vitro amoebicidal activity of ethanol extracts of Arachis
      hypogaea L. (peanut), Curcuma longa L. (turmeric), and Pancratium maritimum L.
      (sea daffodil) on A. castellanii cysts. Acanthamoeba were isolated from keratitic
      patients, cultivated on 1.5% non-nutrient agar, and then incubated with different
      concentrations of plant extracts which were further evaluated for their
      cysticidal activity. The results showed that all extracts had significant
      inhibitory effect on the multiplication of Acanthamoeba cysts as compared to the
      drug control (chlorhexidine) and non-treated control, and the inhibition was time
      and dose dependent. The ethanol extract of A. hypogaea had a remarkable
      cysticidal effect with minimal inhibitory concentration (MIC) of 100 mg/ml in all
      incubation periods, while the concentrations of 10 and 1 mg/ml were able to
      completely inhibit growth after 48 and 72 h, respectively. The concentrations 0.1
      and 0.01 mg/ml failed to completely inhibit the cyst growth, but showed growth
      reduction by 64.4-82.6% in all incubation periods. C. longa had a MIC of 1 g and
      100 mg/ml after 48 and 72 h, respectively, while the concentrations 10, 1, and
      0.1 mg/ml caused growth reduction by 60-90.3% in all incubation periods. P.
      maritimum had a MIC of 200 mg/ml after 72 h, while the 20-, 2-, 0.2-, and 0.02
      mg/ml concentrations showed growth reduction by 34-94.3% in all incubation
      periods. All extracts seemed to be more effective than chlorhexidine which caused
      only growth reduction by 55.3-80.2% in all incubation periods and failed to
      completely inhibit the cyst growth. In conclusion, ethanol extracts of A.
      hypogaea, C. longa, and P. maritimum could be considered a new natural agent
      against the Acanthamoeba cyst.

PMID- 22146996
TI  - Efficacy of the Trichophyton ajelloi and Lagenidium giganteum metabolites against
      mosquitoes after flash chromatography.
AB  - Entomopathogens are significant natural enemies for mosquitoes. We have
      investigated the adulticidal efficacies of metabolites of Trichophyton ajelloi
      and Lagenidium giganteum against Culex quinquefasciatus and Aedes aegypti
      simultaneously. The T. ajelloi was grown on Sabouraud's dextrose broth medium at
      25 +/- 2 degrees C and relative humidity at 75 +/- 5% for 15 days. L. giganteum
      was grown in peptone yeast extract glucose broth at 25 +/- 2 degrees C and
      relative humidity 75 +/- 5% for 15 days. The filtrations of metabolites have been
      made by using Whatman-1 filter paper then with the flash chromatograph. The
      bioassays were conducted as per the World Health Organization's methods and
      protocols (2006). In this significant investigations, the metabolites of T.
      ajelloi have been found highly susceptible against A. aegypti with LC(99)-7.24 ml
      after an exposure time of 24 h with a comparison, the LC(99)-66 ml was observed
      against C. quinquefasciatus after exposure of 24 h. Moreover, the L. giganteum
      metabolites have shown higher pathogenicity against C. quinquefasciatus with
      LC(99)-11.3 ml and A. aegypti with LC(99)-15.49 ml. Although, the efficacy in
      adults could be achieved with higher concentration can be significant also. Their
      adulticidal activities in different climatic zones are plausible with metabolites
      which have better LT values of T. ajelloi.

PMID- 22146995
TI  - Prevalence and genotypes of Enterocytozoon bieneusi in weaned beef calves on cow
      calf operations in the USA.
AB  - To determine the prevalence and genotype distribution of Enterocytozoon bieneusi
      in weaned beef calves in the USA, fecal samples were collected from 819 calves (6
      18 months of age) from 49 operations. Feces were sieved and subjected to density
      gradient centrifugation to remove fecal debris and to concentrate spores. DNA
      extracted from each sample was subjected to the polymerase chain reaction (PCR)
      to amplify the complete internal transcriber spacer (ITS). All PCR-positive
      specimens were sequenced to determine the genotype(s) present. Overall, E.
      bieneusi was detected in 34.8% of the 819 fecal samples. The highest prevalence
      was found in the Midwest region (42.7%) followed by the South (35.8%) and the
      West (23.2%). The prevalence of E. bieneusi varied considerably from operation to
      operation (0-100%). A prevalence of 100% was observed in three operations, one in
      the Midwest and two in the South; E. bieneusi was not found in six operations,
      three in the South and three in the West. Sequence analysis revealed the presence
      of six genotypes, four previously reported (I, J, BEB4, and type IV) and two
      novel genotypes (BEB8 and BEB9). Mixed infections were identified in five
      specimens, three contained I and BEB4 and two contained J and BEB4. Most of the
      positive calves (238 of 285) harbored genotypes with zoonotic potential including
      I (59), J (108), BEB4 (65), type IV (1), mixed I/BEB4 (3), and mixed J/BEB4 (2).

PMID- 22146997
TI  - Laboratory and field evaluation of medicinal plant extracts against filarial
      vector, Culex quinquefasciatus Say (Diptera: Culicidae).
AB  - The present study explored the effects of Jatropha curcas, Hyptis suaveolens,
      Abutilon indicum, and Leucas aspera tested against third instar larvae of
      filarial vector, Culex quinquefasciatus. The dried plant materials were powdered
      by an electrical blender. From each sample, 500 g powder was macerated with 1.5 L
      of hexane, chloroform, ethyl acetate, and methanol 8h, using Soxhlet apparatus,
      and filtered. The extracts were concentrated at reduced temperature on a rotary
      evaporator and stored at a temperature of 4 degrees C. The yield of crude extract
      was 11.4, 12.2, 10.6, and 13.5 g in hexane, chloroform, ethyl acetate, and
      methanol, respectively. The hexane, chloroform, ethyl acetate, and methanol
      extract of J. curcas with LC(50) values of 230.32, 212.85, 192.07, and 113.23
      ppm; H. suaveolens with LC(50) values of 213.09, 217.64, 167.59, and 86.93 ppm;
      A. indicum with LC(50) values of 204.18, 155.53, 166.32, and 111.58 ppm; and L.
      aspera with LC(50) values of 152.18, 118.29, 111.43, and 107.73 ppm,
      respectively, against third instar larvae of C. quinquefasciatus. The larval
      mortality was observed after 24 h of exposure. Maximum larvicidal activity was
      observed in the methanolic extract followed by ethyl acetate, chloroform, and
      hexane extract. No mortality was observed in the control. The observed mortality
      were statistically significant at P < 0.05 level. L. aspera showed the highest
      mortality rate against the mosquito larvae in laboratory and field. The larval
      density was decreased after the treatment of plant extracts at the breeding sites
      (sewage water), and hence, these plant extracts of the suitable alternatives of
      synthetic insecticides for the mosquito vector management. The present results
      suggest that the medicinal plants extract was an excellent potential for
      controlling filarial vector, C. quinquefasciatus.

PMID- 22146998
TI  - Cloning and characterization of a novel gene encoding 16 kDa protein (Ac16) from
      Angiostrongylus cantonensis.
AB  - Angiostrongylus cantonensis is the most common infectious cause of eosinophilic
      meningitis or meningoencephalitis. A novel gene (AC16) was isolated from a cDNA
      library of A. cantonensis fourth-stage larvae. The putative 16-kDa protein has
      149 amino acids and is homologous to an immunodominant hypodermal antigen (IHA16)
      from Ancylostoma caninum (identities = 57%). In this paper, we cloned the gene
      and purified the recombinant Ac16 (rAC16) protein. Real-time quantitative PCR
      revealed that Ac16 was expressed significantly higher in the fourth-stage larvae
      and adult worms derived from rats than that in the fourth-stage larvae derived
      from mice. Moreover, sera from rat (permissive host) infected with A. cantonensis
      detected Ac16 by Western blot, while sera from infected mouse (non-permissive
      host) could not. The results implied that Ac16 was related to the parasitic
      adaptation of A. cantonensis in different hosts and non-permissive host mouse had
      no circulating antibody to the antigen Ac16 from A. cantonensis and thus might
      contribute to understanding the mechanism of parasite immune evasion.
      Furthermore, we evaluated the ability of Ac16 antibody diagnosing A. cantonensis
      infection by an indirect enzyme-linked immunosorbent assay. The results showed
      that the Ac16 antibody had a 79.17% sensitivity to rAC16 and 83.33% to crude
      adult worm antigens (CA) (P > 0.05), while the specificity to rAC16 and to CA
      were 95.89% and 86.30% respectively (P < 0.05), thus implying that rAc16 may
      constitute a putative serodiagnostic antigen for Angiostrongyliasis cantonensis.

PMID- 22146999
TI  - Modulation of urinary peptidome in humans exposed to high altitude hypoxia.
AB  - The exposure of healthy subjects to high altitude represents a model to explore
      the pathophysiology of diseases related to tissue hypoxia and to evaluate
      pharmacological approaches potentially useful as a therapy for chronic diseases
      related to hypoxia. We explored the urinary peptidome to detect alterations
      induced by the exposure of subjects to different altitudes (sea level, high
      altitude = 3500 m, very high altitude = 5400 m) and to pharmacological treatment.
      Urine samples were collected from 47 subjects, randomly and blindly assigned to
      placebo (n = 24) or Telmisartan (n = 23). Samples were purified by the use of
      magnetic beads, then analysed by MALDI-TOF MS. Results showed that the urinary
      peptidome is not affected by the administration of Telmisartan, neither at the
      sea level nor at high and very high altitudes. In contrast, the urinary protein
      profiles are modified when subjects are exposed to high and very high altitudes,
      and we detected six peptides differentially expressed in hypobaric hypoxia at
      high or very high altitude compared to the sea level. Two of them were identified
      as fragments of the glycoprotein uromodulin and of the alpha1-antitrypsin. This
      is the first proteomic study showing that hypobaric hypoxia conditions affect the
      urinary peptidome.

PMID- 22147000
TI  - Incidence, predictive factors, and prognosis of chondrosarcoma in patients with
      Ollier disease and Maffucci syndrome: an international multicenter study of 161
      patients.
AB  - BACKGROUND: Enchondromatosis is characterized by the presence of multiple benign
      cartilage lesions in bone. While Ollier disease is typified by multiple
      enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies
      evaluating the predictive value of clinical symptoms for development of secondary
      chondrosarcoma and prognosis are lacking. This multi-institute study evaluates
      the clinical characteristics of patients, to get better insight on behavior and
      prognosis of these diseases. METHOD: A retrospective study was conducted using
      clinical data of 144 Ollier and 17 Maffucci patients from 13 European centers and
      one national databank supplied by members of the European Musculoskeletal
      Oncology Society. RESULTS: Patients had multiple enchondromas in the hands and
      feet only (group I, 18%), in long bones including scapula and pelvis only (group
      II, 39%), and in both small and long/flat bones (group III, 43%), respectively.
      The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4
      patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in
      group II and 26 patients (46%) in group III, respectively. The risk of developing
      chondrosarcoma is increased when enchondromas are located in the pelvis (odds
      ratio, 3.8; p = 0.00l). CONCLUSIONS: Overall incidence of development of
      chondrosarcoma is 40%, but may, due to age-dependency, increase when considered
      as a lifelong risk. Patients with enchondromas located in long bones or axial
      skeleton, especially the pelvis, have a seriously increased risk of developing
      chondrosarcoma, and are identified as the population that needs regular screening
      on early detection of malignant transformation.

PMID- 22147001
TI  - Making investments in medical technology: time to get real about real options.

PMID- 22147002
TI  - Triple-negative subtype predicts poor overall survival and high locoregional
      relapse in inflammatory breast cancer.
AB  - BACKGROUND: Numerous studies have demonstrated that expression of
      estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor
      (HER)-2 is important for predicting overall survival (OS), distant relapse (DR),
      and locoregional relapse (LRR) in early and advanced breast cancer patients.
      However, these findings have not been confirmed for inflammatory breast cancer
      (IBC), which has different biological features than non-IBC. METHODS: We
      retrospectively analyzed the records of 316 women who presented to MD Anderson
      Cancer Center in 1989-2008 with newly diagnosed IBC without distant metastases.
      Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy
      radiation. Patients were grouped according to receptor status: ER(+) (ER(+)/PR(+)
      and HER-2-; n = 105), ER(+)HER-2(+) (ER(+)/PR(+) and HER-2(+); n = 37), HER-2(+)
      (ER(-)/PR(-) and HER-2(+); n = 83), or triple-negative (TN) (ER(-)PR(-)HER-2(-);
      n = 91). Kaplan-Meier and Cox proportional hazards methods were used to assess
      LRR, DR, and OS rates and their associations with prognostic factors. RESULTS:
      The median age was 50 years (range, 24-83 years). The median follow-up time and
      median OS time for all patients were both 33 months. The 5-year actuarial OS
      rates were 58.7% for the entire cohort, 69.7% for ER(+) patients, 73.5% for
      ER(+)HER-2(+) patients, 54.0% for HER=2(+) patients, and 42.7% for TN patients (p
      < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%,
      respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%,
      28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were
      worse for TN patients than for any other subgroup (p < .0001-.03). CONCLUSIONS:
      TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients,
      indicating the need for developing new locoregional and systemic treatment
      strategies for patients with this aggressive subtype.

PMID- 22147003
TI  - When to wait for more evidence? Real options analysis in proton therapy.
AB  - PURPOSE: Trends suggest that cancer spending growth will accelerate. One method
      for controlling costs is to examine whether the benefits of new technologies are
      worth the extra costs. However, especially new and emerging technologies are
      often more costly, while limited clinical evidence of superiority is available.
      In that situation it is often unclear whether to adopt the new technology now,
      with the risk of investing in a suboptimal therapy, or to wait for more evidence,
      with the risk of withholding patients their optimal treatment. This trade-off is
      especially difficult when it is costly to reverse the decision to adopt a
      technology, as is the case for proton therapy. Real options analysis, a technique
      originating from financial economics, assists in making this trade-off. METHODS:
      We examined whether to adopt proton therapy, as compared to stereotactic body
      radiotherapy, in the treatment of inoperable stage I non-small cell lung cancer.
      Three options are available: adopt without further research; adopt and undertake
      a trial; or delay adoption and undertake a trial. The decision depends on the
      expected net gain of each option, calculated by subtracting its total costs from
      its expected benefits. RESULTS: In The Netherlands, adopt and trial was found to
      be the preferred option, with an optimal sample size of 200 patients. Increase of
      treatment costs abroad and costs of reversal altered the preferred option.
      CONCLUSION: We have shown that real options analysis provides a transparent
      method of weighing the costs and benefits of adopting and/or further researching
      new and expensive technologies.

PMID- 22147004
TI  - Prognostic value of red blood cell parameters and ferritin in predicting deferral
      due to low hemoglobin in whole blood donors.
AB  - Risk factors for deferral from red blood cell (RBC) donation due to low
      hemoglobin are not well defined. We analyzed in a large cohort of returning
      donors the prognostic value of RBC parameters and serum ferritin regarding low
      hemoglobin levels at the subsequent visit. Between 2004 and 2009, RBC indices and
      serum ferritin were recorded in 45,533 visits by 7,994 donors. In 689 instances,
      donation was deferred at the subsequent visit due to low hemoglobin levels (<123
      g/l for female donors, <133 g/l for male donors). Pre-donation hemoglobin at the
      current visit correlated best with hemoglobin at the subsequent visit (R (2) =
      0.63), whereas other RBC indices and serum ferritin correlated only poorly (R (2)
      <= 0.15). Similar results were obtained in ROC curve analysis and in
      multivariable binary logistic regression. A pre-donation hemoglobin within 5 g/l
      from the deferral threshold (<128 g/l for female, <138 g/l for male donors)
      predicted below-threshold hemoglobin levels at the subsequent visit with a
      sensitivity of 52% and a specificity of 94%. In conclusion, pre-donation
      hemoglobin is a useful marker identifying donors at risk of developing low
      hemoglobin levels. Diagnostic and therapeutic interventions should be aimed at
      donors presenting with hemoglobin levels near the threshold of donor deferral.

PMID- 22147005
TI  - Lymphoma with specific affinity to endocrine organs.

PMID- 22147006
TI  - Clinical features of adult patients with secondary hemophagocytic
      lymphohistiocytosis from causes other than lymphoma: an analysis of treatment
      outcome and prognostic factors.
AB  - Although hemophagocytic syndrome (HS) featuring secondary hemophagocytic
      lymphohistiocytosis (HLH) has a grave prognosis, little is known about the
      natural course of the disease. Patients who showed the clinical features of HLH
      as well as tissue-proven hemophagocytosis when seen at Asan Medical Center
      between 1999 and 2010 were included in this analysis. Patients with proven
      lymphoma were excluded. The median age of our 23 study patients was 49 years.
      Epstein-Barr virus was suspected to have caused HS in 16 (70%) patients and
      hepatitis A virus in one patient. Twenty-two patients were treated, 13 according
      to the HLH protocol and nine using immunosuppressive agents such as
      corticosteroid and/or cyclosporine. Five patients undertook allogeneic
      hematopoietic cell transplantation (HCT) during their treatment-dependent relapse
      (n = 4) or responsive status (n = 1). After the median follow-up of 180 days, 17
      (74%) died and six (26%) were alive. The median time from initial presentation
      until death was 41 days among those patients who died. The serum fibrinogen level
      >=166 mg/dL determined at the initial visit was significantly associated with the
      survival time according to univariate analysis. The low histiocyte proportion in
      bone marrow and early initiation of treatment tended to correlate with a
      favorable outcome. On multivariate analysis, serum fibrinogen >=166 mg/dL (hazard
      ratio, 0.175, P = 0.018) was an independent clinical factor for determining the
      patient survival time. Despite appropriate patient management, the outcome of HS
      featuring HLH was grave. The serum fibrinogen level at the initial presentation
      was significant, and selected patients obtained some benefit from allogeneic HCT.

PMID- 22147007
TI  - Hepatic suppression of Foxo1 and Foxo3 causes hypoglycemia and hyperlipidemia in
      mice.
AB  - Dysregulation of blood glucose and triglycerides are the major characteristics of
      type 2 diabetes mellitus. We sought to identify the mechanisms regulating blood
      glucose and lipid homeostasis. Cell-based studies established that the Foxo
      forkhead transcription factors Forkhead box O (Foxo)-1, Foxo3, and Foxo4 are
      inactivated by insulin via a phosphatidylinositol 3-kinase/Akt-dependent pathway,
      but the role of Foxo transcription factors in the liver in regulating nutrient
      metabolism is incompletely understood. In this study, we used the Cre/LoxP
      genetic approach to delete the Foxo1, Foxo3, and Foxo4 genes individually or a
      combination of two or all in the liver of lean or db/db mice and assessed the
      role of Foxo inactivation in regulating glucose and lipid homeostasis in vivo. In
      the lean mice or db/db mice, hepatic deletion of Foxo1, rather than Foxo3 or
      Foxo4, caused a modest reduction in blood glucose concentrations and barely
      affected lipid homeostasis. Combined deletion of Foxo1 and Foxo3 decreased blood
      glucose levels, elevated serum triglyceride and cholesterol concentrations, and
      increased hepatic lipid secretion and caused hepatosteatosis. Analysis of the
      liver transcripts established a prominent role of Foxo1 in regulating gene
      expression of gluconeogenic enzymes and Foxo3 in the expression of lipogenic
      enzymes. Our findings indicate that Foxo1 and Foxo3 inactivation serves as a
      potential mechanism by which insulin reduces hepatic glucose production and
      increases hepatic lipid synthesis and secretion in healthy and diabetic states.

PMID- 22147008
TI  - Glucagon-like peptide-1 enhances glucokinase activity in pancreatic beta-cells
      through the association of Epac2 with Rim2 and Rab3A.
AB  - Glucokinase (GK), which phosphorylates D-glucose, is a major glucose sensor in
      beta-cells for glucose-stimulated insulin secretion (GSIS) and is a promising new
      drug target for type 2 diabetes (T2D). In T2D, pancreatic beta-cells exhibit
      defective glucose sensitivity, which leads to impaired GSIS. Although glucagon
      like peptide-1-(7-36)-amide (GLP-1) is known to enhance beta-cell glucose
      sensitivity, the effect of GLP-1 on GK activity is still unknown. The present
      study demonstrated that GLP-1 pretreatment for 30 min significantly enhanced GK
      activity in a glucose-dependent manner, with a lower Michaelis-Menten constant
      (K(m)) but unchanged maximal velocity (V(max)). Thus, GLP-1 acutely enhanced
      cellular glucose uptake, mitochondrial membrane potential, and cellular ATP
      levels in response to glucose in rat INS-1 and native beta-cells. This effect of
      GLP-1 occurred via its G protein-coupled receptor pathway in a cAMP-dependent but
      protein kinase A-independent manner with evidence of exchange protein activated
      by cAMP (Epac) involvement. Silencing Epac2, interacting molecule of the small G
      protein Rab3 (Rim2), or Ras-associated protein Rab3A (Rab3A) significantly
      blocked the effect of GLP-1. These results suggested that GLP-1 can further
      potentiate GSIS by enhancing GK activity through the signaling of Epac2 to Rim2
      and Rab3A, which is the similar pathway for GLP-1 to potentiate Ca(2+)-dependent
      insulin granule exocytosis. The present finding may also be an important
      mechanism of GLP-1 for recovery of GSIS in T2D.

PMID- 22147009
TI  - Liganded thyroid hormone receptor induces nucleosome removal and histone
      modifications to activate transcription during larval intestinal cell death and
      adult stem cell development.
AB  - Thyroid hormone (T(3)) plays an important role in regulating multiple cellular
      and metabolic processes, including cell proliferation, cell death, and energy
      metabolism, in vertebrates. Dysregulation of T(3) signaling results in
      developmental abnormalities, metabolic defects, and even cancer. We used T(3)
      dependent Xenopus metamorphosis as a model to study how T(3) regulates
      transcription during vertebrate development. T(3) exerts its metamorphic effects
      through T(3) receptors (TR). TR recruits, in a T(3)-dependent manner, cofactor
      complexes that can carry out chromatin remodeling/histone modifications. Whether
      and how histone modifications change upon gene regulation by TR during vertebrate
      development is largely unknown. Here we analyzed histone modifications at T(3)
      target genes during intestinal metamorphosis, a process that involves essentially
      total apoptotic degeneration of the simple larval epithelium and de novo
      development of the adult epithelial stem cells, followed by their proliferation
      and differentiation into the complex adult epithelium. We demonstrated for the
      first time in vivo during vertebrate development that TR induces the removal of
      core histones at the promoter region and the recruitment of RNA polymerase.
      Furthermore, a number of histone activation and repression marks have been
      defined based on correlations with mRNA levels in cell cultures. Most but not all
      correlate with gene expression induced by liganded TR during development,
      suggesting that tissue and developmental context influences the roles of histone
      modifications in gene regulation. Our findings provide important mechanistic
      insights on how chromatin remodeling affects developmental gene regulation in
      vivo.

PMID- 22147010
TI  - Thyroid hormone receptor-alpha gene knockout mice are protected from diet-induced
      hepatic insulin resistance.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most frequent chronic liver
      disease in the United States and is strongly associated with hepatic insulin
      resistance. We examined whether the thyroid hormone receptor-alpha (Thra) would
      be a potential therapeutic target to prevent diet-induced NAFLD and insulin
      resistance. For that purpose, we assessed insulin action in high-fat diet-fed
      Thra gene knockout (Thra-0/0) and wild-type mice using hyperinsulinemic
      euglycemic clamps combined with (3)H/(14)C-labeled glucose to assess basal and
      insulin-stimulated rates of glucose and fat metabolism. Body composition was
      assessed by (1)H magnetic resonance spectroscopy and energy expenditure by
      indirect calorimetry. Relative rates of hepatic glucose and fat oxidation were
      assessed in vivo using a novel proton-observed carbon-edited nuclear magnetic
      resonance technique. Thra-0/0 were lighter, leaner, and manifested greater whole
      body insulin sensitivity than wild-type mice during the clamp, which could be
      attributed to increased insulin sensitivity both in liver and peripheral tissues.
      Increased hepatic insulin sensitivity could be attributed to decreased hepatic
      diacylglycerol content, resulting in decreased activation of protein kinase
      Cepsilon and increased insulin signaling. In conclusion, loss of Thra protects
      mice from high-fat diet-induced hepatic steatosis and hepatic and peripheral
      insulin resistance. Therefore, thyroid receptor-alpha inhibition represents a
      novel pharmacologic target for the treatment of NAFLD, obesity, and type 2
      diabetes.

PMID- 22147011
TI  - Somatostatin inhibition of GnRH neuronal activity and the morphological
      relationship between GnRH and somatostatin neurons in rats.
AB  - In rodents, GnRH neurons are diffusely distributed from the medial septum through
      to the medial preoptic area and control gonadal functions through the pituitary.
      The activity of GnRH neurons is regulated by a variety of bioactive substances,
      including the inhibitory peptide somatostatin. In the present study, we focused
      on somatostatin because intracerebroventricular injection of somatostatin
      inhibits the LH surge in rats and reduces LH secretion in ewes. Somatostatin also
      decreases GnRH release from rat hypothalamic slices. In mice, somatostatin is
      also thought to suppress GnRH neuronal activity through contact on the soma of
      GnRH neurons. However, similar data are missing in rats. Moreover, rat GnRH
      neurons receive only a few synaptic inputs. In this study, we assessed the
      morphological relationship between GnRH and somatostatin neurons. Confocal
      microscopy on the sections from the medial septum through medial preoptic area
      revealed about 35 close contacts per rat between the GnRH and somatostatin
      neuronal fibers in the organum vasculosum of the lamina terminalis region. No
      contact of somatostatin fibers on the GnRH neuronal somata was observed.
      Multicell RT-PCR for somatostatin receptor mRNA in rat GnRH neurons was also
      performed, which revealed moderate expression of somatostatin receptor subtypes 1
      5. In addition, patch clamp experiments were carried out in acute slice
      preparations. Somatostatin suppressed neuronal firing in cells recorded in a cell
      attached configuration and also induced whole-cell outward currents in GnRH
      neurons. These findings suggest that somatostatin directly inhibits the activity
      of rat GnRH neurons through volume transmission in the organum vasculosum of the
      lamina terminalis region.

PMID- 22147013
TI  - Impact of ovarian sex steroids on ovulation and ovulatory gene induction in
      aromatase-null mice.
AB  - Female mice deficient in the aromatase gene [aromatase knockout (ArKO)] fail to
      ovulate owing to an inability to produce estrogens. Here, we demonstrated that
      sequential administration of adequate amounts of 17beta-estradiol (E2), pregnant
      mare serum gonadotropin, and human chorionic gonadotropin could induce ovulation
      in immature ArKO mice; nevertheless, significantly fewer oocytes were released
      into the oviducts in ArKO mice than in wild-type mice. Analysis of ovarian
      steroids by liquid chromatography coupled with electrospray ionization-tandem
      mass spectrometry identified a trace amount of E2 in the untreated immature ArKO
      ovary. The analysis further detected significant increases and decreases in
      progesterone and testosterone contents, respectively, in addition to an increase
      of E2 in the ovulation-induced ArKO ovaries compared with the levels in untreated
      ArKO ovaries. Gene expression analysis demonstrated marked elevation in the mRNA
      levels of members of the epidermal growth factor family and extracellular matrix
      related proteins at 4 h after human chorionic gonadotropin injection in the
      ovaries of ArKO mice treated for ovulation, as observed in the ovulation-induced
      wild-type ovaries. Collectively, these findings suggest the vital contribution of
      the intraovarian milieu of sex steroids to ovulatory regulation in vivo.

PMID- 22147012
TI  - Differential responses of progesterone receptor membrane component-1 (Pgrmc1) and
      the classical progesterone receptor (Pgr) to 17beta-estradiol and progesterone in
      hippocampal subregions that support synaptic remodeling and neurogenesis.
AB  - Progesterone (P4) and estradiol (E2) modulate neurogenesis and synaptic
      remodeling in the hippocampus during the rat estrous cycle and in response to
      deafferenting lesions, but little is known about the steroidal regulation of
      hippocampal progesterone receptors associated with these processes. We examined
      the neuronal expression of progesterone receptor membrane component-1 (Pgrmc1)
      and the classical progesterone receptor (Pgr), by in situ hybridization and
      immunohistochemistry. Pgr, a transcription factor, has been associated with
      synaptic remodeling and other major actions of P4, whereas Pgrmc1 is implicated
      in P4-dependent proliferation of adult neuroprogenitor cells and with rapid P4
      effects on membranes. Ovariectomized adult rats were given E2, P4, or E2+P4 on
      two schedules: a 4-d model of the rodent estrous cycle and a 30-d model of
      postmenopausal hormone therapy. Pgr was hormonally responsive only in CA1
      pyramidal neurons, and the induction of Pgr by E2 was partly antagonized by P4
      only on the 30-d schedule. In CA3 pyramidal and dentate gyrus (DG) neurons, Pgr
      was largely unresponsive to all hormone treatments. In contrast to Pgr, Pgrmc1
      was generally induced by E2 and/or P4 throughout the hippocampus in CA1, CA3, and
      DG neurons. In neuroprogenitor cells of the DG (immunopositive for
      bromodeoxyuridine and doublecortin), both Pgrmc1 and Pgr were detected. The
      differential regulation of hippocampal Pgrmc1 and Pgr by E2 and P4 may guide drug
      development in hormonal therapy for support of neurogenesis and synaptic
      regeneration.

PMID- 22147015
TI  - Hypothalamic JNK1 and IKKbeta activation and impaired early postnatal glucose
      metabolism after maternal perinatal high-fat feeding.
AB  - Hypothalamic inflammation has been demonstrated to be an important mechanism in
      the pathogenesis of obesity-induced type 2 diabetes mellitus. Feeding pregnant
      and lactating rodents a diet rich in saturated fatty acids has consistently been
      shown to predispose the offspring for the development of obesity and impaired
      glucose metabolism. However, hypothalamic inflammation in the offspring has not
      been addressed as a potential underlying mechanism. In this study, virgin female
      C57BL/6 mice received high-fat feeding starting at conception until weaning of
      the offspring at postnatal d 21. The offspring developed increased body weight,
      body fat content, and serum leptin concentrations during the nursing period.
      Analysis of hypothalamic tissue of the offspring at postnatal d 21 showed up
      regulation of several members of the toll-like receptor 4 signaling cascade and
      subsequent activation of c-Jun N-terminal kinase 1 and IkappaB kinase-beta
      inflammatory pathways. Interestingly, glucose tolerance testing in the offspring
      revealed signs of impaired glucose tolerance along with increased hepatic
      expression of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. In
      addition, significantly increased hepatic and pancreatic PGC1alpha expression
      suggests a role for sympathetic innervation in mediating the effects of
      hypothalamic inflammation to the periphery. Taken together, our data indicate an
      important role for hypothalamic inflammation in the early pathogenesis of glucose
      intolerance after maternal perinatal high-fat feeding.

PMID- 22147014
TI  - Zinc depletion causes multiple defects in ovarian function during the
      periovulatory period in mice.
AB  - Shortly before ovulation, the oocyte acquires developmental competence and
      granulosa cells undergo tremendous changes including cumulus expansion and
      luteinization. Zinc is emerging as a key regulator of meiosis in vitro, but a
      complete understanding of zinc-mediated effects during the periovulatory period
      is lacking. The present study uncovers the previously unknown role of zinc in
      maintaining meiotic arrest before ovulation. A zinc chelator [N,N,N',N'-tetrakis
      (2-pyridylmethyl) ethylenediamine (TPEN)] caused premature germinal vesicle
      breakdown and associated spindle defects in denuded oocytes even in the presence
      of a phosphodiesterase 3A inhibitor (milrinone). TPEN also potently blocked
      cumulus expansion by blocking induction of expansion-related transcripts Has2,
      Ptx3, Ptgs2, and Tnfaip6 mRNA. Both meiotic arrest and cumulus expansion were
      rescued by exogenous zinc. Lack of cumulus expansion is due to an almost complete
      suppression of phospho-Sma- and Mad-related protein 2/3 signaling. Consistent
      with a decrease in phospho-Sma- and Mad-related protein 2/3 signaling, TPEN also
      decreased cumulus transcripts (Ar and Slc38a3) and caused a surprising increase
      in mural transcripts (Lhcgr and Cyp11a1) in cumulus cells. In vivo, feeding a
      zinc-deficient diet for 10 d completely blocked ovulation and compromised cumulus
      expansion. However, 42.5% of oocytes had prematurely resumed meiosis before human
      chorionic gonadotropin injection, underscoring the importance of zinc before
      ovulation. A more acute 3-d treatment with a zinc-deficient diet did not block
      ovulation but did increase the number of oocytes trapped in luteinizing
      follicles. Moreover, 23% of ovulated oocytes did not reach metaphase II due to
      severe spindle defects. Thus, acute zinc deficiency causes profound defects
      during the periovulatory period with consequences for oocyte maturation, cumulus
      expansion, and ovulation.

PMID- 22147016
TI  - Exposure to di(2-ethyl-hexyl) phthalate (DEHP) in utero and during lactation
      causes long-term pituitary-gonadal axis disruption in male and female mouse
      offspring.
AB  - The present study examined the effects in mice of exposure to di(2-ethyl-hexyl)
      phthalate (DEHP) throughout pregnancy and lactation on the development and
      function of the pituitary-gonadal axis in male and female offspring once they
      have attained adulthood. Groups of two to three dams were exposed with the diet
      from gestational d 0.5 until the end of lactation, at 0, 0.05, 5, and 500 mg
      DEHP/kg . d. The experiment was repeated three times (total: seven to 10 dams per
      treatment). The 500-mg dose caused complete pregnancy failure, whereas exposure
      to doses of 0.05 and 5 mg did not affect pregnancy and litter size. In total,
      about 30 male and 30 female offspring per group were analyzed. Offspring of the
      DEHP-treated groups, compared with controls, at sexual maturity showed: 1) lower
      body weight (decrease 20-25%, P < 0.001); 2) altered gonad weight (testes were
      ~13% lighter and ovaries ~40% heavier; P < 0.001); 3) poor germ cell quality
      (semen was ~50% less concentrated and 20% less viable, and ~10% fewer oocytes
      reached MII stage, P < 0.001); 4) significant lower expression of steroidogenesis
      and gonadotropin-receptor genes in the gonads; and 5) up-regulated gonadotropin
      subunit gene expression in the pituitary. In conclusion, our findings suggest
      that, in maternally exposed male and female mice, DEHP acts on multiple pathways
      involved in maintaining steroid homeostasis. Specifically, in utero and
      lactational DEHP exposure may alter estrogen synthesis in both sexes. This, in
      turn, induces dysregulation of pituitary-gonadal feedback and alters the
      reproductive performance of exposed animals.

PMID- 22147018
TI  - Circadian feeding drive of metabolic activity in adipose tissue and not
      hyperphagia triggers overweight in mice: is there a role of the pentose-phosphate
      pathway?
AB  - High-fat (HF) diets trigger an increase in adipose tissue and body weight (BW)
      and disordered eating behavior. Our study deals with the hypothesis that
      circadian distribution of energy intake is more relevant for BW dynamics than
      diet composition. Four-week-old mice were exposed for 8 wk to a HF diet and
      compared with animals receiving control chow. HF mice progressively increased BW,
      decreased the amount of nocturnal (1800-0900 h) calories (energy or food intake)
      (30%) and increased diurnal (0900-1800 h) caloric intake (energy or food intake),
      although total daily intake was identical between groups. Animals were killed at
      3-h intervals and plasma insulin, leptin, corticosterone, glucose, and fatty acid
      levels quantified. Adipose tissue was weighed, and enzymatic activities integral
      to the pentose phosphate pathway (PPP) assayed in lumbar adipose tissue.
      Phosphorylated AMP-dependent protein kinase and fatty acid synthase were
      quantified by Western blotting. In HF mice, there was a shift in the circadian
      oscillations of plasma parameters together with an inhibition of PPP activity and
      a decrease in phosphorylated AMP-dependent protein kinase and fatty acid
      synthase. In a second experiment, HF mice were forced to adhere to a circadian
      pattern of food intake similar to that in control animals. In this case, BW,
      adipose tissue, morning plasma parameters and PPP activity appeared to be normal.
      These data indicate that disordered feeding behavior can trigger BW gain
      independently of food composition and daily energy intake. Because PPP is the
      main source of reduced nicotinamide adenine dinucleotide phosphate, we suggest
      that PPP inhibition might be an early marker of adipose dysfunction in diet
      induced obesity.

PMID- 22147019
TI  - The importance of beta cell characterisation: generating human beta cells by
      differentiating human embryonic stem cells.

PMID- 22147017
TI  - VEGFA family isoforms regulate spermatogonial stem cell homeostasis in vivo.
AB  - The objective of the present study was to investigate vascular endothelial growth
      factor A (VEGFA) isoform regulation of cell fate decisions of spermatogonial stem
      cells (SSC) in vivo. The expression pattern and cell-specific distribution of
      VEGF isoforms, receptors, and coreceptors during testis development postnatal d 1
      180 suggest a nonvascular function for VEGF regulation of early germ cell
      homeostasis. Populations of undifferentiated spermatogonia present shortly after
      birth were positive for VEGF receptor activation as demonstrated by
      immunohistochemical analysis. Thus, we hypothesized that proangiogenic isoforms
      of VEGF (VEGFA(164)) stimulate SSC self-renewal, whereas antiangiogenic isoforms
      of VEGF (VEGFA(165)b) induce differentiation of SSC. To test this hypothesis, we
      used transplantation to assay the stem cell activity of SSC obtained from
      neonatal mice treated daily from postnatal d 3-5 with 1) vehicle, 2) VEGFA(164),
      3) VEGFA(165)b, 4) IgG control, 5) anti-VEGFA(164), and 6) anti-VEGFA(165)b. SSC
      transplantation analysis demonstrated that VEGFA(164) supports self-renewal,
      whereas VEGFA(165)b stimulates differentiation of mouse SSC in vivo. Gene
      expression analysis of SSC-associated factors and morphometric analysis of germ
      cell populations confirmed the effects of treatment on modulating the biological
      activity of SSC. These findings indicate a nonvascular role for VEGF in testis
      development and suggest that a delicate balance between VEGFA(164) and
      VEGFA(165)b isoforms orchestrates the cell fate decisions of SSC. Future in vivo
      and in vitro experimentation will focus on elucidating the mechanisms by which
      VEGFA isoforms regulate SSC homeostasis.

PMID- 22147020
TI  - Development of a wireless intra-vaginal transducer for monitoring intra-abdominal
      pressure in women.
AB  - Pelvic floor disorders (PFD) affect one of every four women in the United States.
      Elevated intra-abdominal pressure (IAP) during daily activity or strenuous
      physical activity has been identified as a risk factor in the prevalence of PFD.
      However, the relationship between IAP and physical activity is poorly understood
      and oftentimes activity restrictions are prescribed by physicians without
      clinical evidence linking various activities to elevated IAP. There are currently
      no pressure transducers capable of monitoring IAP non-invasively out of a
      clinical environment. To overcome this shortcoming, a novel intra-vaginal
      pressure transducer (IVT) was developed to continuously monitor IAP. Improvements
      were made to the first generation IVT by incorporating wireless capability to
      enhance the device's mobility while creating a more robust IAP monitoring system.
      To ensure the changes maintained the functionality of the original device design,
      comparison testing with standard clinical pressure transducers in both bench top
      and clinical settings was conducted. The wireless device was found to have high
      linearity, robust signal transmission, and dynamic response that outperforms the
      clinical standard rectal transducer and is similar to the original first
      generation non-wireless design. The wireless IVT presented here is a mobile
      wireless device capable of measuring, storing and transmitting IAP data during
      various physical activities.

PMID- 22147021
TI  - Spectral and photophysical properties of alpha-carboline (1-azacarbazole) in
      aqueous solutions.
AB  - The absorption and fluorescence spectra of alpha-carboline, 9H-pyrido[2,3
      b]indole, AC, in organic aprotic solvents containing different water proportions
      and in acid/base aqueous solutions inside and outside the pH range have been
      examined. In the organic aprotic solvents, the addition of increasing
      concentrations of water sequentially quenches and shifts to the red the
      fluorescence spectra of AC. These spectral changes have been rationalized
      assuming the formation, at the lower water concentrations, of a discrete ground
      state non-cyclic weakly fluorescent AC hydrate emitting at 376 nm that, upon
      increasing the water concentrations, evolves to a higher order AC poly hydrate
      emitting at 397 nm. The changes of the AC absorption spectra in aqueous
      acid/basic solutions indicate the existence of three ground state prototropic
      species; the pyridinic protonated cation, C (pK(a) = 4.10 +/- 0.05), the neutral,
      N (pK(a) = 14.5 +/- 0.2), and the pyrrolic deprotonated anion, A. Conversely, the
      changes of the AC fluorescence spectra in these media indicate the existence of
      four excited state species emitting at 376 nm, 397 nm, 460 nm and 465 nm. Since
      the emissions at 376 nm and 397 nm satisfactorily match those of the hydrates
      observed in the organic-water mixtures, they were consistently assigned to two
      differently hydrated ground state N species. The remaining emissions at 460 nm
      and 465 nm have been assigned without ambiguity, on the basis of their excitation
      spectra, to the C and A species, respectively. The excited-state pK(a)s of the
      prototropic species of AC have been estimated by using the Forster-Weller cycle.

PMID- 22147022
TI  - A new bis(rhodamine)-based fluorescent chemosensor for Fe3+.
AB  - A new bis(rhodamine)-based fluorescent probe 4 was synthesized, and it exhibited
      high selectivity for Fe(3+) over other commonly coexistent metal ions in both 50%
      ethanol and Tris-HCl buffer. Upon the addition of Fe(3+), the spirocyclic ring of
      4 was opened and a significant enhancement of visible color and fluorescence in
      the range of 500-600 nm was observed.

PMID- 22147023
TI  - HIV-Associated facial lipoatrophy: from the advent to current knowledge.
AB  - The advent of AIDS has brought new challenges to Dermatology. Antiretroviral
      therapy dramatically changed the morbidity and mortality associated with HIV /
      AIDS, but contributed to the emergence of other new situations that require
      adequate approach by the dermatologist. The HIV / AIDS Associated Lipodystrophy
      Syndrome is multifactorial in origin, but it is strongly associated with the use
      of antiretroviral drugs. It includes changes in body fat distribution, with or
      without metabolic changes. The loss of facial fat, called facial lipoatrophy, is
      one of the most stigmatizing signs of the syndrome. This condition, often
      revealing of the disease, brought back the stigma of AIDS. It is necessary that
      the specialists working with patients with HIV / AIDS identify these changes and
      seek treatment options, amongst which stands out the implant with
      polymethylmethacrylate, which is available for the treatment of HIV / AIDS facial
      lipoatrophy in the Brazilian Public Health System.

PMID- 22147025
TI  - Association between skin thickness and bone density in adult women.
AB  - BACKGROUND: Osteoporosis mainly affects menopausal women and the elderly,
      predisposing these individuals to fractures that result in morbidity, mortality
      and costs to the healthcare system. Since dermal collagen reduces in parallel
      with a decrease in bone mass with aging, skin thickness may be indicative of a
      risk of osteoporosis. OBJECTIVES: To evaluate the correlation between bone
      density and skin thickness on the backs of the hands of adult women. METHODS: A
      cross sectional study involving adult women attending a university hospital
      outpatient clinic who were interviewed individually and submitted to bone
      densitometry and measurement of skin thickness on the backs of their hands using
      skinfold calipers. Other risk factors for osteoporosis were also investigated.
      RESULTS: A total of 140 patients were evaluated. Mean age (+/- standard
      deviation) was 57 +/- 11 years. Mean skin thickness on the backs of the hands was
      1.4 +/- 0.4 mm. There was a correlation between the right and left hands (R =
      0.9; p<0.01). A direct correlation was found between skin thickness on the backs
      of the hands and bone density at the lumbar spine and femur (p<0.01). These
      results remained consistent even following adjustment for the covariables of age,
      skin phototype, body mass index, smoking, use of oral corticoids, anti
      inflammatory use and time since menopause. Osteoporosis was inversely associated
      with the thickness of the skin on the back of the hands (odds ratio = 0.10;
      p<0.03) CONCLUSION: An independent correlation was found between skin thickness
      and bone density, suggesting that these events occur simultaneously. Skin signs
      may represent a non-invasive method of stratifying risk in these patients,
      helping identify cases requiring early treatment.

PMID- 22147024
TI  - Dermatological diseases of compulsory notification in Brazil.
AB  - The development of a Brazilian National Surveillance System in 1975 led to a
      compulsory reporting of selected infectious diseases aiming to reduce the burden
      of these events in the country. However, shifts in the epidemiology of these
      diseases associated with modern life style, demand constant revision of
      surveillance activities. In this manuscript we present the epidemiology, trends
      and differential diagnosis of the following compulsory notifiable diseases in
      Brazil: Aids, dengue fever, hanseniasis, American tegumentary leishmaniasis,
      measles, rubella and congenital rubella syndrome and syphilis. Additionally, the
      current challenges for control and prevention of each disease are presented.

PMID- 22147026
TI  - Quality of life assessment in patients with chronic urticaria.
AB  - BACKGROUND: Chronic urticaria affects patients by interfering with their daily
      activities, damaging their self-esteem and negatively affecting their
      interpersonal relationships. Healthcare professionals may underestimate the
      impact of the condition on patients' quality of life. OBJECTIVES: To evaluate
      quality of life using one generic and one disease-specific health-related quality
      of life instrument; to compare quality of life between the different clinical
      types of chronic urticaria and to evaluate whether angioedema further impairs
      quality of life. METHODS: Sixty-two patients with chronic urticaria, who had had
      signs or symptoms of the disease within the preceding week, were divided into
      groups according to whether they had ordinary chronic urticaria, physical chronic
      urticaria or mixed chronic urticaria. RESULTS: There was a predominance of women
      in this study (72.6%). The mean age of patients was 39.8 years and angioedema was
      associated with chronic urticaria in 75.8% of cases. Associated angioedema was
      more commonly found in patients with ordinary chronic urticaria (p=0.011) and in
      women (p=0.024). With respect to the different clinical types, 32.3% of the
      patients had ordinary chronic urticaria, 27.4% had physical chronic urticaria and
      40.3% had mixed chronic urticaria. Mean overall score for the disease-specific
      questionnaire was 10.4. In this questionnaire, the most affected domains were
      "symptoms and feelings" and "daily activities", while the most affected domains
      in the SF-36 were "physical role" and "vitality". Quality of life was found to be
      impaired in women, in patients of up to 30 years of age, in those attending a
      first consultation, in those with higher education levels, in patients who had
      had the disease for up to one year and in those with angioedema. CONCLUSION:
      Chronic urticaria affects quality of life, as measured using a disease-specific
      questionnaire and a generic questionnaire. There was no statistically significant
      difference between the clinical types. The presence of angioedema impaired
      patients' quality of life even further. There was a statistically significant
      correlation between the scores obtained using the disease-specific questionnaire
      and those obtained using the generic questionnaire.

PMID- 22147027
TI  - Natural-biomembrane dressing and hypersensitivity.
AB  - BACKGROUND: The natural biomembrane of latex extracted from Hevea brasiliensis
      has been used as a dressing for skin ulcers. OBJECTIVES: To evaluate how safe the
      natural biomembrane is in relation to hypersensitivity to latex when used as a
      dressing. METHODS: We selected patients with skin ulcers, forming the following
      groups: control - low occupational exposure to latex (n = 17); latex-exposed
      control - high occupational exposure (n = 14); ulcerated, using the natural
      biomembrane (n = 13); ulcerated control, not using the natural biomembrane (n =
      14); and new cases (n = 9), assessed before and after 3 months of using the
      natural biomembrane. All patients underwent clinical and epidemiological
      evaluation for latex hypersensitivity and specific IgE (UniCap((r))), and the
      control and latex-exposed control groups underwent the patch test. RESULTS:
      Hypersensitivity was positive in 64.7% of the patients in the control group,
      71.4% of the patients in the latex-exposed control group, 61.5% of the ulcerated
      using the natural biomembrane, 35.7% of the ulcerated control, and only 22 , 2%
      of the new cases. In the patch test of the control and latex-exposed control
      groups, only one individual in the control group (low contact) showed erythema in
      the first reading, which became negative in the second. The mean contact with
      latex in the latex-exposed control group was 3.42 hours / day. In the
      fluoroimmunoenzymatic assay, most of the sera was classified as zero (range 0-6).
      No serum was rated above 2, which is not considered significant for
      hypersensitivity (classification > 4). CONCLUSION: The natural biomembrane proved
      to be safe as a dressing, for it did not induce hypersensitivity reactions among
      the volunteers who underwent the patch test or among users of the natural
      biomembrane, as it was clinically and immunologically demonstrated by IgE levels.

PMID- 22147028
TI  - The use of polymerase chain reaction to confirm diagnosis in skin biopsies
      consistent with American tegumentary leishmaniasis at histopathology: a study of
      90 cases.
AB  - BACKGROUND: Cutaneous leishmaniasis is a chronic, infectious disease caused by
      protozoa of the genus leishmania. The incidence of this disease is high in
      Brazil, with 19,746 new cases having been detected in 2008. The presence of
      amastigotes in the cytoplasm of histiocytes constitutes diagnosis of the disease;
      however, their presence is rarely found in late lesions, making histological
      diagnosis difficult. Polymerase chain reaction has been shown to represent a
      highly sensitive and specific technique for the diagnosis of cutaneous
      leishmaniasis. OBJECTIVES: To use polymerase chain reaction to evaluate paraffin
      embedded skin biopsies with histopathological features consistent with cutaneous
      leishmaniasis. MATERIAL AND METHODS: Polymerase chain reaction amplification of a
      120-base-pair fragment of Leishmania kinetoplast DNA (kDNA) minicircles was
      performed on 90 skin biopsies. The male/female ratio was 75/15. Mean age was
      32.36 years, with a median of 31 years, range 4-72 years. Samples were
      histologically compatible with cutaneous leishmaniasis but a definitive diagnosis
      could not be made since amastigotes were not found. All cases were histologically
      classified according to the patterns described by de Magalhaes. RESULTS:
      According to the de Magalhaes classification, the most common histological
      pattern was type IV (exudative granulomatous reaction), which was found in 65.6%
      of cases (56/90), followed by type I (exudative cellular reaction) in 21.1% of
      cases (19/90) and type III (exudative and necrotic granulomatous reaction) in
      12.2% of cases (11/90). Leishmania DNA was found in 96.7% of the biopsies
      (87/90). CONCLUSION: Polymerase chain reaction performed by amplifying kDNA is
      able to confirm a diagnosis of cutaneous leishmaniasis with a high degree of
      sensitivity in cases in which histopathology is consistent with a diagnosis of
      cutaneous leishmaniasis but not definitive.

PMID- 22147029
TI  - An epidemiological study of immune-mediated skin diseases affecting the oral
      cavity.
AB  - BACKGROUND: Immune-mediated skin diseases encompass a variety of pathologies that
      present in different forms in the body. OBJECTIVE: The objective of this study
      was to establish the prevalence of the principal immune-mediated skin diseases
      affecting the oral cavity. METHODS: A total of 10,292 histopathology reports
      stored in the archives of the Anatomical Pathology Laboratory, Department of Oral
      Pathology, Federal University of Rio Grande do Norte, covering the period from
      1988 to 2009, were evaluated. For the cases diagnosed with some type of disease
      relevant to the study, clinical data such as the gender, age and ethnicity of the
      patient, the anatomical site of the disease and its symptomatology were
      collected. RESULTS: Of all the cases registered at the above-mentioned service,
      82 (0.8%) corresponded to immune-mediated skin diseases with symptoms affecting
      the oral cavity. The diseases found in this study were: oral lichen planus,
      pemphigus vulgaris and benign mucous membrane pemphigoid. Oral lichen planus was
      the most common lesion, comprising 68.05% of the cases analyzed. Of these cases,
      64.3% were women and the cheek mucosa was the anatomical site most commonly
      affected (46.8%). CONCLUSION: Immune-mediated skin diseases affecting the oral
      cavity continue to be rare, the prevalence found in this study being similar to
      that reported for the majority of regions worldwide. Nevertheless, early
      diagnosis is indispensable in the treatment of these diseases, bearing in mind
      that systemic involvement is possible in these patients.

PMID- 22147030
TI  - Fundamentals of the knowledge about chemical additives present in rubber gloves.
AB  - BACKGROUNDS: One of the most frequent causes of allergic contact dermatitis of
      occupational origin are rubber additives, which are present in Personal
      Protective Equipment (PPE). The most allergenic additives of natural and
      synthetic gloves are thiurams, carbamates and mercapto group. OBJECTIVE: To
      investigate the state of knowledge about the chemical additives used in the
      manufacture of synthetic rubber gloves. METHODS: This was a qualitative research
      study in which professionals working in the manufacture, research, prescription
      and commercialization of gloves answered an open questionnaire. RESULTS: 30
      individuals were interviewed: 4 researchers in occupational medicine, 5
      occupational physicians, 2 occupational safety technicians, a rubber workers'
      union physician, an occupational safety engineer, a pro duction engineer of
      rubber gloves, 4 importers of gloves, a manufacturer of gloves, 3 businessmen who
      sell PPE, 3 salesclerks working in stores that sell PPE, 2 businessmen who own
      stores that sell products for allergic individuals, and 3 dermatologists.
      CONCLUSION: Knowledge of the chemical composition of rubber gloves is scant. The
      labeling of gloves, with the description of their chemical composition, would
      facilitate choosing the best type of glove for each person. This low-cost action
      to businesses would be a gain from the standpoint of public health, with huge
      repercussions for users of rubber gloves.

PMID- 22147031
TI  - Sebaceous hyperplasia: a pilot study to correlate this skin disease with
      circulating androgen levels.
AB  - BACKGROUND: The sebaceous glands are susceptible to the effects of androgens. A
      benign proliferation of these hormones, i.e. hyperplasia, occurs with age.
      OBJECTIVES: This was a pilot study to demonstrate whether any correlation exists
      between circulating androgen levels and an increase in the incidence of sebaceous
      hyperplasia. METHODS: Sixteen female patients with a diagnosis of sebaceous
      hyperplasia were compared to a control group of females of a similar age without
      the disease. Blood tests were performed on participants of both groups to measure
      circulating androgen levels (free and total testosterone and androstenedione
      levels). Results were tabulated for statistical analysis. RESULTS: These data
      showed no statistically significant differences in circulating androgen levels
      between the patients with sebaceous hyperplasia and the control group.
      CONCLUSION: These data suggest that no significant changes occur in circulating
      androgen levels [free and total testosterone, androstenedione,
      dehydroepiandrosterone (DHEA) and DHEA sulfate] in patients with sebaceous
      hyperplasia.

PMID- 22147033
TI  - Cutaneous melanoma: a 30-year-long epidemiological study conducted in a city in
      southern Brazil, from 1980-2009.
AB  - BACKGROUND: Melanoma incidence and mortality rates have increased over the past
      30 years in the Caucasian population. In Brazil, data on non-capital cities are
      scarce, making epidemiological stu dies necessary. OBJECTIVES: To evaluate the
      incidence of and classify cutaneous melanomas in Blumenau from 1980 to 2009.
      METHOD: Data from 1002 histopathological examinations of individuals from
      Blumenau were collected, considering sex, age, primary site of involvement,
      histological type, level of invasion (Clark's level) and tumor thickness
      (Breslow's depth). The gross and adjusted coefficients of annual incidences were
      calculated based on the number of melanoma cases and the population estimated by
      the Brazilian Institute of Geography and Statistics (IBGE) between 1980 and 2009.
      RESULTS: The incidence rates of melanoma reached 22.4 cases per 100,000
      inhabitants/year; 31.5 in women and 30.4 in men at the adjusted rate. The
      incidence rates standardized by decade, age and sex were 141 male and 103 female
      cases per 100,000/inhabitants aged 65 to 69 years. Superficial spreading melanoma
      occurred in 53% of the cases, followed by nodular melanoma (37%), and the primary
      site of involvement was the trunk (47%). 62.5% of the cases were diagnosed early,
      with Breslow < 1 mm. CONCLUSION: The incidence of malignant melanoma has
      increased fivefold from 1980 to 2009 and early diagnosis has increased 151% as a
      result of primary prevention.

PMID- 22147032
TI  - HIV-associated tuberculous lymphadenitis: the importance of polymerase chain
      reaction (PCR) as a complementary tool for the diagnosis of tuberculosis - a
      study of 104 patients.
AB  - BACKGROUND: Lymphadenitis is common in HIV-positive patients. Diagnosis of the
      infections associated with this condition is complex, particularly in the case of
      tuberculosis. Rapid and specific detection of Mycobacterium tuberculosis (M.
      tuberculosis) is fundamental in ensuring adequate treatment. In addition,
      frequent causes of lymphadenitis such as those associated with lymphoma and
      histoplasmosis, among others, must be eliminated as possible causes. OBJECTIVES:
      To evaluate the accuracy of polymerase chain reaction as a tool for the diagnosis
      of lymphadenitis resulting from M. tuberculosis. METHODS: In this study, a
      protocol was developed using the following procedures: direct microscopy using
      Ziehl-Neelsen staining, culture in Lowenstein-Jensen medium, histology and
      polymerase chain reaction. RESULTS: A total of 104 patients were included in the
      study. According to histopathology, 38 patients (36%) were found to have
      nonspecific chronic lymphadenitis, 27 (26%) had tuberculous lymphadenitis, 11
      patients (10.5%) had lymphoma and 9 (8.7%) had histoplasmosis. When Lowenstein
      Jensen culture was performed, positive tests for tuberculous lymphadenitis
      increased by 30%. With polymerase chain reaction, M. tuberculosis DNA was
      detected in 6 out of 38 samples of non-specific chronic lymphadenitis. Three of
      these patients were followed up, developed symptoms of tuberculosis and were
      cured following specific treatment. CONCLUSION: The data obtained in this study
      suggest that all cases of lymphadenopathies should be submitted to
      histopathology, Lowenstein-Jensen or Ogawa culture and polymerase chain reaction.
      Polymerase chain reaction may prove to be useful in providing an early and
      accurate detection of cases of extrapulmonary tuberculosis in HIV-positive
      patients with lymphadenopathies, avoiding empirical treatment and the possible
      development of resistant strains.

PMID- 22147034
TI  - Profile of patients affected by Hansen's disease seen at the Outpatient Clinic of
      Dermatology at Hospital Evangelico de Curitiba.
AB  - BACKGROUND: Leprosy or Hansen's disease is a chronic infectious disease with
      worldwide distribution. Although it is a curable disease, it remains as a public
      health problem, with Brazil being the second most endemic country in the world.
      The skin lesions and neural damage, which lead to physical disabilities, affect
      the patients' self-esteem, cause a decrease in quality of life and interfere in
      the patients' lives. OBJECTIVE: Identify the profile of the patients affected by
      leprosy seen at the Outpatient Clinic of Dermatology of Hospital Evangelico de
      Curitiba and characterize the levels of quality of life of the sample in the week
      prior to the survey by means of the Dermatology Life Quality Index questionnaire.
      METHOD: Application of the Dermatology Life Quality Index to 22 patients
      diagnosed with leprosy in the period from May to October 2009. RESULTS: Among the
      22 patients who participated in the study, 55% were male and 45% were female,
      with a mean age of 50.2 years. The scores obtained with the Dermatology Life
      Quality Index ranged from 1 to 25 points, with a mean of 10.23. Most of the
      patients (50%) had scores in the range severe or very severe; 31.8% of the
      patients obtained scores in the range mild or moderate, and 18.2% of the patients
      reported that there was no impairment of their quality of life. CONCLUSION: The
      profile of the patients affected by leprosy in this study were men, with a mean
      age of 50 years and presenting the multibacillary form of the disease. The
      application of the Dermatology Life Quality Index questionnaire allowed us to
      verify that the score severe or very severe for quality of life was predominant
      in the sample, with higher impact on women and no significant difference
      concerning pauci or multibacillary leprosy.

PMID- 22147035
TI  - Effect of low-level laser therapy on the initial stages of tissue repair: basic
      principles.

PMID- 22147036
TI  - Knowledge of the physical properties and interaction of laser with biological
      tissue in dentistry.
AB  - The trend in dentistry is to incorporate less invasive methods to minimize pain
      and discomfort during and after dental intervention. Therefore, it is believed
      that laser therapy is an excellent treatment option, since it has beneficial
      effects for the irradiated tissues, such as activation of microcirculation,
      production of new capillaries, inflammatory and analgesic effects, in addition to
      stimulation of growth and cell regeneration. The comprehension of the interaction
      between lasers and tissue is based mainly on understanding the reactions that can
      be induced in those tissues by laser. This work intends to show how important it
      is to know the physical properties of laser as well as its interactions with
      biological tissues, since its effects and mechanisms of action are complex and
      are the object of various studies to better understand its forms of application
      and indications.

PMID- 22147037
TI  - Livedoid vasculopathy: an intringuing cutaneous disease.
AB  - Livedoid vasculopathy is a skin disease that occludes the blood vessels of the
      dermis. It has a pauciinflammatory or non-inflammatory nature. It is
      characterized by the presence of macular or papular, erythematous-purpuric
      lesions affecting the legs, especially the ankles and feet, and producing
      intensely painful ulcerations, which cause white atrophic scars called "atrophie
      blanche". This review includes studies and case reports found in the medical
      literature regarding the etiopathogenic associations of the disease, particularly
      those related to thrombophilia, their histopathological findings and the
      therapeutic approaches used in the difficult clinical management of these cases.

PMID- 22147038
TI  - Dowling-Degos disease: classic clinical and histopathological presentation.
AB  - Dowling-Degos disease (DDD) is a rare genetic disease of the skin (reticulate
      pigmented anomaly), clinically characterized by flexural brown pigmented
      reticulate macules, comedo-like papules on the back, neck and pitted perioral or
      facial scars. We present the case of a 51 year-old man with macrocomedo-like
      lesions, pitted scars, cysts, hyperpigmented macules in his back, chest, axillae,
      neck, groin and face. The patient reported having two children, three brothers
      and a father with a similar condition. The histopathology of the skin biopsies
      was very characteristic of Dowling-Degos disease, showing dilated follicular,
      fingerlike projections called rete ridges (dermal pegs), with thinning of the
      suprapapillary plates, resulting in an "antler-like" pattern and increased
      pigmentation of the basal layer.

PMID- 22147039
TI  - Acne fulminans and isotretinoin: case report.
AB  - Acne fulminans (AF) is a rare disorder, the most severe form of the entire
      clinical spectrum of acne. It is characterized by emergence of painful
      inflammatory nodules that turn into ulcers, concomitant with systemic
      manifestations. It can be induced by isotretinoin and some authors believe that
      the occurrence of this condition is dose dependent. The treatment is
      controversial and there is no consensus up to this time. A case of this rare
      disease, developed during use of isotretinoin in low doses, is presented.

PMID- 22147040
TI  - Localized primary cutaneous nodular amyloidosis: case report.
AB  - Amyloidosis results from deposition of fibrous and insoluble amyloid protein in
      extracellular spaces of organs and tissues. Amyloid deposition can be localized
      or systemic and either primary or secondary. We report a case of localized
      primary cutaneous nodular amyloidosis manifested by papular-nodular, reddish
      brown lesions affecting the nasal area, without evidence of systemic involvement.
      Immunohistochemistry showed the presence of immunoglobulin kappa light chain.

PMID- 22147041
TI  - Trichilemmal carcinoma: case report.
AB  - The trichilemmal carcinoma is a rare tumor that usually occurs on sun-exposed
      skin, especially on the face, scalp, neck and back of hands, mainly in elderly
      subjects but commonly between the 4th and 9th decades of life. It is not a gender
      based illness. This study shows a difficult to treat case of recurrent
      trichilemmal carcinoma on the same location of a basal-cell carcinoma previously
      treated with surgery and radiotherapy.

PMID- 22147042
TI  - Sporotrichosis in pregnancy: case reports of 5 patients in a zoonotic epidemic in
      Rio de Janeiro, Brazil.
AB  - Five cases of sporotrichosis occurring in pregnant women in a zoonotic epidemic
      in Rio de Janeiro, Brazil, are described. The main clinical features, as well as
      the challenging therapeutic choices for this specific group of patients, are
      discussed.

PMID- 22147043
TI  - Cutaneous leiomyosarcoma on the trunk.
AB  - Cutaneous leiomyosarcoma is a relatively uncommon tumor that accounts for 7% of
      all soft tissue sarcomas. It occurs more frequently in males between 50-70 years
      and only 10-15% of cases are located on the trunk. Radiotherapy and previous
      trauma have been implied as risk factors. We report the case of a 57 year-old
      male with an eight-month history of a hard painless erythematous-violaceous tumor
      on the presternal region. Histopathology evidenced a malignant spindle cell
      tumor, "cigar" shaped, with pleomorphic nuclei and a high mitotic index that
      occupied the entire dermal thickness. Immunohistochemical staining of the tumor
      cells was positive for smooth muscle actin, desmin and vimentin and negative for
      S-100 protein and pan-cytokeratin, which supported the diagnosis of dermal
      leiomyosarcoma. Radical surgery was performed to remove the tumor.

PMID- 22147044
TI  - Trichophyton tonsurans in a family microepidemic.
AB  - Trichophyton tonsurans is a highly transmissible anthropophilic dermatophyte
      fungus, which invades keratinized tissues. This study reports a case of family
      microepidemic caused by this dermatophyte. Despite their excellent hygiene
      conditions, it remained active for several years, spreading to all family
      members. The hypothesis that the fungus was being kept alive in the family home
      was confirmed after samples collected from it were analyzed. Pure cultures of the
      fungus were isolated and identified. After diagnosis, the house was disinfected
      with concomitant oral treatment for all family members.

PMID- 22147045
TI  - Simultaneous occurrence of ulcerated necrobiosis lipoidica and granuloma annulare
      in a patient: case report.
AB  - Simultaneous occurrence of granuloma annulare and necrobiosis lipoidica is quite
      rare. There are seven reported cases in the literature, but only one presenting
      ulcerated necrobiosis lipoidica. We report a 39-year-old male with
      histopathologically confirmed granuloma annulare and ulcerated necrobiosis
      lipoidica, without diabetes mellitus.

PMID- 22147046
TI  - Report of three new leprosy cases in children under fifteen in the municipality
      of Itaguai, Rio de Janeiro: event alert for epidemiological investigation.
AB  - Leprosy is an infectious disease with an average incubation period of two to five
      years. It is caused by Mycobacterium leprae, mainly affecting skin, mucous
      membranes and peripheral nerves. When it occurs in children under fifteen, it
      reflects an intense and long contact period, with a high bacillary load.
      Therefore, it is considered an important alert sign that points to the challenge
      of controlling the disease. The authors report three cases of leprosy in children
      under fifteen that occurred in the Itaguai district, Rio de Janeiro. The
      epidemiologic implications of new cases detected at this age and the fundamental
      role of examining the patients' close contacts and the possible identification of
      source cases as an effort for leprosy control are discussed.

PMID- 22147047
TI  - Sweet's Syndrome associated with Hodgkin's disease: case report.
AB  - Sweet's syndrome is a rare cutaneous disease of unknown etiology. About 20% of
      the cases are associated with hematological neoplasms, and cases related with
      Hodgkin's disease are rare. We present the case of a 57-year old male patient who
      developed the syndrome concomitantly with the neoplasm. The diseases were
      controlled with specific treatment.

PMID- 22147048
TI  - Extensive amalgam tattoo on the alveolar-gingival mucosa.
AB  - Amalgam tattoos are common exogenous pigmented lesions of the oral mucosa
      occurring mainly by inadvertent placement of amalgam particles into soft tissues.
      The diagnosis of amalgam tattoo is simple, usually based on clinical findings
      associated with presence or history of amalgam fillings removal. Intraoral X-rays
      may be helpful in detecting amalgam-related radiopacity. In cases where amalgam
      tattoo cannot be differentiated from other causes of oral pigmentation, a biopsy
      should be performed. This article deals with an extensive amalgam tattoo lesion
      which required a biopsy for a definitive diagnosis.

PMID- 22147049
TI  - Cutaneous metastasis of bladder sarcoma: when should we consider this hypothesis?
      A review of the literature.
AB  - The incidence of cutaneous metastases is approximately 0.7 to 10%, while in
      metastases of urothelial origin the incidence is less than 1%. Transitional cell
      carcinoma is the most common of the genitourinary tract tumors. Sarcoma of the
      bladder is rare (0.3%). It can involve multiple clinical presentations, with a
      nodule being the most common. Diagnosis is made by a combination of medical
      history, clinical examination and histopathology. The treatment is surgical. The
      prognosis is very uncertain and depends on a multidisciplinary approach.

PMID- 22147050
TI  - Histoplasmosis and AIDS co-infection.
AB  - This report concerns an AIDS patient presenting systemic and cutaneous
      manifestations of histoplasmosis. A histopathological and mycological examination
      of the skin lesion confirmed the diagnosis. In AIDS patients histoplasmosis
      arises mainly when the T-CD4+ cell count is less than 50 cells/mm3. In such
      cases, histoplasmosis can be severe and if left untreated can lead to death, as
      occurred with this patient.

PMID- 22147051
TI  - Disseminated tungiasis.
AB  - Tungiasis is a zoophilic and anthropophilic infestation caused by Tunga
      penetrans. It is endemic in Latin America and in the Caribbean. It occurs mainly
      in impoverished communities that have no access to basic sanitation and in
      individuals that visit contaminated areas. The most common penetration site of
      this ectoparasite is the periungueal region of the feet. The authors present its
      disseminated form occurring in a patient inhabiting a rural area.

PMID- 22147052
TI  - Case for diagnosis. Glomus tumor.
AB  - Glomus tumor is a painful tumor derived from the glomus terminal which regulates
      blood circulation and body temperature Despite its rarity, particular attention
      needs to be paid to symptoms associated with this tumor: paroxysmal pain,
      sensitivity to local pressure and cold, and its location - typically in the
      distal phalanx. Manifestation of extradigital occurrence is possible. Single
      lesions are most common in adult females, while multiple lesions are prevalent in
      children and adolescents, generally those with a positive family history. The
      diagnosis is clinical with the aid of ultrasonography and magnetic resonance
      imaging, confirmed by histopathological examination.

PMID- 22147053
TI  - Case for diagnosis. Cutaneous metastases of visceral cancer.
AB  - Cutaneous metastases of visceral cancers are relatively rare, with an incidence
      of 0.7 to 10%. The most frequent primary sites are breast, lung and colon tumors.
      They generally occur after the primary cancer is diagnosed and signify a poor
      prognosis. They may occur as the first manifestation in 20% of cancers in
      general. The most common manifestations are single or multiple asymptomatic
      nodules, most often located on the chest, abdomen, head and neck, sometimes with
      unusual clinical features which present a challenge to clinical diagnosis.

PMID- 22147054
TI  - Do you know this syndrome? Chediak-Higashi syndrome.
AB  - Chediak-Higashi syndrome is characterized by varying degrees of oculocutaneous
      albinism, recurrent infections, bleeding disorders and variable neurological
      involvement. The treatment consists of bone marrow transplantation, which
      corrects the immunologic and hematologic defects. Untreated patients die as the
      result of bacterial infections or develop "accelerated phase"
      lymphoproliferation. We present a case of Chediak-Higashi syndrome and discuss
      the clinical and laboratorial features that determine its diagnosis.

PMID- 22147055
TI  - Do you know this syndrome? Xeroderma pigmentosum (XP).
AB  - Xeroderma pigmentosum is a rare genetic disease characterized by clinical and
      cellular hypersensitivity to ultraviolet radiation and DNA repair defects.
      Patients with xeroderma pigmentosum experience sun-induced cutaneous and ocular
      abnormalities, including cancer. Some develop neurological disorders. We describe
      the case of a 2 year-old child with DeSanctis-Cacchione's syndrome, with severe
      neurological deterioration associated with schizencephaly. In the current
      clinical classification of xeroderma pigmentosum, the term is reserved for cases
      with severe neurological disorders linked to dwarfism and immature sexual
      development. The association of xeroderma pigmentosum with schizencephaly has not
      to date been reported in the literature.

PMID- 22147056
TI  - The importance of trichological examination in the diagnosis of alopecia areata.
AB  - In this article we discuss the propedeutic aspects of alopecia areata, especially
      those found by dermatoscopy, an invaluable tool for diagnosis of the condition.
      Dermatoscopy facilitates the early detection of the characteristic changes in
      alopecia areata hair such as exclamation-point hairs, cadaverous hair, fuzzy
      hair, vellus type hair and yellow spots.

PMID- 22147057
TI  - Association of oral acyclovir and imiquimod for the treatment of hypertrophic
      genital herpes simplex in HIV positive patients: report of two cases.
AB  - Chronic herpes simplex can present as exuberant clinical lesions, especially in
      HIV patients. The most probable mechanism of formation of these lesions is the
      invasion of the epidermal CD4 T cells by the herpes simplex virus. Due to the
      therapeutic difficulties and the high rates of treatment failure amongst these
      patients, new drugs are currently being discussed on the literature. Studies
      based on the immunophatology of these lesions have suggested that imiquimod might
      work as an adjuvant therapy to the antiviral drugs. Here we present two cases of
      excellent response to treatment with topical imiquimod as an adjuvant drug to
      acyclovir.

PMID- 22147058
TI  - Treatment of ingrown nail: comparison of recurrence rates between the nail matrix
      phenolization classical technique and phenolization associated with nail matrix
      curettage - is the association necessary?
AB  - Some services in Brazil combine curettage of the nail matrix with phenolization
      in the treatment of ingrown nails, with the objective of further increasing
      efficacy. The objective of this research was to compare the cure rates between
      the phenolization technique and phenolization associated with nail matrix
      curettage. A retrospective study was done which included 271 cases. There was
      only a 5% recurrence rate for the phenolization procedure, compared with 7.7% for
      combined phenolization/nail matrix curettage. There was no statistically
      significant difference between the two techniques, which indicated that there is
      no need for curettage of the nail matrix. Phenolization worked even for level III
      disease.

PMID- 22147060
TI  - The association between ethnic identity and sexual coercion among young men in
      the Eastern Cape Province, South Africa.
AB  - Sexual coercion by males poses important ethical, legal and public health
      challenges. Individual face-to-face structured interviews were conducted among
      1656 men who had undergone male initiation and circumcision in rural areas of the
      Eastern Cape Province. Overall, 8.4 per cent of the participants reported ever
      having forced someone to have sex. Logistic regression adjusting for age, working
      status, education level and nation of origin showed that participants that
      expressed high cultural affiliation were significantly less likely to sexually
      coerce someone. The findings suggest that emphasizing cultural commitment may
      reduce sexual coercion, though findings need to be replicated.

PMID- 22147061
TI  - Risky business: risk information and the moderating effect of message frame and
      past behaviour on women's perceptions of the Human Papillomavirus vaccine.
AB  - The effect of response cost information, message framing and past behaviour on
      women's coping appraisal and motivation to be vaccinated against the Human
      Papillomavirus (HPV) were investigated using a 2 Frame * 2 Response Cost * 2 Pap
      Status design. Women (N = 286) read one of four messages about the vaccine. Women
      who received high-risk information perceived the vaccine as having higher
      response cost and were less motivated to be vaccinated compared to women who
      received low-risk information. The deleterious effects of risk information on
      specific aspects of women's coping appraisal may be mitigated by appropriately
      framed messages.

PMID- 22147062
TI  - Pessimistic attributions and coping strategies as predictors of depressive
      symptoms in people with coronary heart disease.
AB  - This two-wave longitudinal study examines the ability of pessimistic
      attributional style and coping strategies to predict depressive symptoms in a
      sample of 99 patients with coronary heart disease (CHD). After the cardiac
      episode, the globality dimension of this style was associated with increased
      depressive symptoms, and this association was mediated by the low use of
      effective coping strategies. Stability and globality dimensions of pessimistic
      attributional style could also predict depressive symptoms eight weeks later.
      Cardiac intervention programmes should include the treatment of these symptoms
      and promote effective coping strategies as well as the modification of these
      stable and global attributions.

PMID- 22147063
TI  - No room for reflexivity? Critical reflections following a systematic review of
      qualitative research.
AB  - We conducted a systematic search of qualitative research into the individual's
      experience of chronic low back pain. Two reviewers independently read through 740
      unique abstracts. Inter-rater reliability was fair. The final sample comprised 19
      articles which we critiqued using the Critical Appraisal Skills Programme
      checklist. This article focuses on the critical appraisal. Limitations include a
      lack of an adequate rationale for the theoretical framework, a lack of an account
      for the decisions made across recruitment and data collection, and a lack of
      reflexivity. Finally we discuss and offer recommendations for reflexivity and the
      explication of qualitative methodology in research articles.

PMID- 22147064
TI  - The right tool for the job.

PMID- 22147065
TI  - On a chip.
AB  - The future of clinical and POC BioMEMS is very bright. With an increasing
      emphasis on the personalization of medicine and the rising costs of health care,
      early detection and diagnostics at the POC will be even more important. Early
      detection implies early intervention, resulting in the saving of lives and
      reducing overall spending. The potential impact of these technologies on the
      early diagnosis and management of both communicable and noncommunicable diseases
      is very high. Many grand challenges applications are possible, e.g., routine
      tests such as complete blood cell count on a chip that an individual can perform
      at home; detection of cardiac markers from blood after a perceived heart attack;
      detection of cancer markers such as exosomes, CTCs from blood, or protein
      biomarkers in serum; and detection of infectious agents such as virus and
      bacteria for public health. These applications are expected to result in new
      diagnostic assays for home, doctor's office, clinical laboratories, and various
      POC settings.

PMID- 22147067
TI  - Beyond proof of concept. Interview by Steve Quake and Shu Takayama.

PMID- 22147066
TI  - Engineering tissue with BioMEMS.
AB  - In summary, microfluidic-BioMEMS platforms are increasingly contributing to
      tissue engineering in many different ways. First, the accurate control of the
      cell environment in settings suitable for cell screening and with imaging
      compatibility is greatly advancing our ability to optimize cell sources for a
      variety of tissue-engineering applications. Second, the microfluidic technology
      is ideal for the formation of perfusable networks, either to study their
      stability and maturation or to use these networks as templates for engineering
      vascularized tissues. Third, the approaches based on microfluidic and BioMEMS
      devices enable engineering and the study of minimally functional modules of
      complex tissues, such as liver sinusoid, kidney nephron, and lung bronchiole.
      This brief article highlighted some of the unique advantages of this elegant
      technology using representative examples of tissue-engineering research. We
      focused on some of the universal needs of the area of tissue engineering: tissue
      vascularization, faithful recapitulation in vitro of functional units of our
      tissues and organs, and predictable selection and differentiation of stem cells
      that are being addressed using the power and versatility of microfluidic-BioMEMS
      platforms.

PMID- 22147068
TI  - Perspective on diagnostics for global health.

PMID- 22147070
TI  - Medical image analysis.

PMID- 22147069
TI  - Solving medical problems with BioMEMS.

PMID- 22147071
TI  - Laplace's law. Its epistemological context.

PMID- 22147072
TI  - Genetic epilepsy with febrile seizures plus: definite and borderline phenotypes.
AB  - Generalised epilepsy with febrile seizures plus (GEFS+) is the most studied
      familial epilepsy syndrome. However, characteristics of UK families have not
      previously been reported. Among the first 80 families recruited to our families
      study, four broad subphenotypes were identified: families with classical GEFS+;
      families with borderline GEFS+; families with unclassified epilepsy; and families
      with an alternative syndromal diagnosis. Borderline GEFS+ families shared many
      characteristics of classical GEFS+ families-such as prominent febrile seizures
      plus and early onset febrile seizures-but included more adults with focal
      epilepsies (rather than the idiopathic generalised epilepsies predominating in
      GEFS+) and double the prevalence of migraine. Thus the authors believe that a
      novel and robust familial epilepsy phenotype has been identified. Subcategorising
      families with epilepsy is helpful in targeting both clinical and research
      resources. Most families with GEFS+ have no identified causal mutation, and so
      predicting genetic homogeneity by identifying endophenotypes becomes more
      important.

PMID- 22147074
TI  - Using stannous ion as an excellent inorganic ECL coreactant for tris(2,2'
      bipyridyl) ruthenium(II).
AB  - It was found that stannous chloride (SnCl(2)), as a popular inorganic reducing
      reagent, could obviously enhance the electrochemiluminescence (ECL) of tris(2,2'
      bipyridyl) ruthenium(II) (Ru(bpy)(3)(2+)) in aqueous solution. Some factors
      affecting the ECL reactions between Ru(bpy)(3)(2+) and Sn(2+), including pH,
      concentrations of coreactant, and electrode materials, were investigated by
      comparison with a classic ECL coreactant tripropylamine (TPA). The Ru(bpy)(3)(2+)
      Sn(2+) ECL coreactant system produces stronger and more stable ECL signals, can
      keep its excellent ECL activity over a wider pH range and has more choices in
      using electrode materials than the Ru(bpy)(3)(2+)-TPA ECL coreactant system. The
      ECL mechanism of the Ru(bpy)(3)(2+)-Sn(2+) coreactant system was also studied in
      detail.

PMID- 22147073
TI  - Tissue-specific transcriptome analysis reveals cell wall metabolism, flavonol
      biosynthesis and defense responses are activated in the endosperm of germinating
      Arabidopsis thaliana seeds.
AB  - Seed germination is a result of the competition of embryonic growth potential and
      mechanical constraint by surrounding tissues such as the endosperm. To understand
      the processes occurring in the endosperm during germination, we analyzed tiling
      array expression data on dissected endosperm and embryo from 6 and 24 h-imbibed
      Arabidopsis seeds. The genes preferentially expressed in the endosperm of both 6
      and 24 h-imbibed seeds were enriched for those related to cell wall
      biosynthesis/modifications, flavonol biosynthesis, defense responses and cellular
      transport. Loss of function of AtXTH31/XTR8, an endosperm-specific gene for a
      putative xyloglucan endotransglycosylase/hydrolase, led to faster germination.
      This suggests that AtXTH31/XTR8 is involved in the reinforcement of the cell wall
      of the endosperm during germination. In vivo flavonol staining by diphenyl boric
      acid aminoethyl ester (DPBA) showed flavonols accumulated in the endosperm of
      both dormant and non-dormant seeds, suggesting that this event is independent of
      germination. Notably, DPBA fluorescence was also intense in the embryo, but the
      fluorescent region was diminished around the radicle and lower half of the
      hypocotyl during germination. DPBA fluorescence was localized in the vacuoles
      during germination. Vacuolation was not seen in imbibed dormant seeds, suggesting
      that vacuolation is associated with germination. A gene for deltaVPE (vacuolar
      processing enzyme), a caspase-1-like cysteine proteinase involved in cell death,
      is expressed specifically in endosperms of 24 h-imbibed seeds. The deltavpe
      mutant showed retardation of vacuolation, but this mutation did not affect the
      kinetics of germination. This suggests that vacuolation is a consequence, and not
      a trigger, of germination.

PMID- 22147075
TI  - The effect of dacomitinib (PF-00299804) on CYP2D6 activity in healthy volunteers
      who are extensive or intermediate metabolizers.
AB  - PURPOSE: This study evaluated the effect of a single 45-mg dose of dacomitinib
      (PF-00299804), an irreversible small-molecule inhibitor of human epidermal growth
      factor receptors-1, -2, and -4, on CYP2D6 activity in healthy volunteers (HV)
      using dextromethorphan (DM), a selective CYP2D6 probe. METHODS: Fourteen male HVs
      were enrolled in this open-label, randomized, cross-over, single-dose study of DM
      alone or with dacomitinib. Each HV received both treatments separated by a 14-day
      washout period. The pharmacokinetics of DM, dextrorphan (DX; the major DM
      metabolite), dacomitinib and PF-05199265 (an active metabolite of dacomitinib)
      were calculated. RESULTS: When combined with dacomitinib, the ratio of adjusted
      geometric means (90% CI) of DM area under the concentration-time curve
      (AUC)(last) was 955% (90% CI: 560%, 1,630%) and maximum plasma concentration (C
      (max)) was 973% (90% CI: 590%, 1,606%), compared with DM alone. For dacomitinib
      plus DM, exposures were consistent with those in patients receiving single-dose
      dacomitinib. Terminal elimination half-life (t (1/2)) was 51.4 h. Mild and
      moderate treatment-related adverse events were reported. No HV withdrew from the
      study. CONCLUSIONS: Single-dose administration of dacomitinib plus DM was safe
      and well tolerated in HVs and resulted in a significant increase in systemic
      exposures of DM in extensive metabolizers. No effect was observed on the
      pharmacokinetics of dacomitinib. Drug-drug interaction may occur when dacomitinib
      is concomitantly administered with therapeutic agents metabolized by cytochrome
      P450 (CYP) 2D6. Administration of drugs which are highly dependent on CYP2D6
      metabolism may require dose adjustment, or substitution with an alternative
      medication.

PMID- 22147076
TI  - Going past the data for temozolomide.
AB  - The benefit of six cycles of adjuvant temozolomide was documented in a randomized
      phase III (EORTC-NCIC CE.3) trial, and this therapy, following combined
      temozolomide and radiation, is the standard of care for patients with newly
      diagnosed glioblastoma. We comment on the differences in the length of adjuvant
      therapy in both clinical practice and national studies (e.g. RTOG 0825), usually
      doubling the length in the EORTC/NCIC study, and relate to historic adjuvant
      trials for solid tumors.

PMID- 22147077
TI  - Influence of H2-receptor antagonists and proton pump inhibitors on dasatinib
      pharmacokinetics in Japanese leukemia patients.
AB  - PURPOSE: The objective of this study was to investigate the drug interaction
      between dasatinib and the gastric acid suppressants (H2-receptor antagonists
      (H2RA) famotidine and nizatidine and the proton pump inhibitor (PPI) lansoprazole
      in leukemia Japanese patients. METHODS: Eighteen patients treated with dasatinib
      and H2RA, PPI or no acid suppressant from whom were obtained a total of 34
      pharmacokinetic profiles were enrolled in the study. Dasatinib plasma
      concentrations from samples obtained just prior to and 1, 2, and 4 h after oral
      dasatinib administration were analyzed by high-performance liquid chromatography.
      RESULTS: There were no significant correlations between the dose-adjusted total
      area under the observed plasma concentration-time curve (AUC(0-4)) of dasatinib
      and gender, age, weight, or body surface area. The only variable factor, the
      dasatinib dose-adjusted AUC(0-4) for patients administered an H2RA or PPI, was
      significantly lower than for patients not administered an acid suppressant
      (median (quartile 1-quartile 3) values: 1.47 (0.79-2.29) versus 3.51 (2.50-5.45)
      ng h/mL/mg, respectively, P = 0.0008). Moreover, the plasma concentration 2 h
      (C(2h)) after dasatinib administration gave a high correlation with the AUC(0-4)
      of dasatinib (r = 0.9419, P < 0.0001). CONCLUSION: Clinicians should be aware
      that administration of an acid suppressant such as famotidine, nizatidine, and
      lansoprazole can decrease the absorption of dasatinib from the gastrointestinal
      tract, thereby resulting in a significant decrease in the plasma concentration of
      dasatinib. The combination of dasatinib and an acid suppressant requires careful
      therapeutic drug monitoring of the dasatinib plasma concentration to ensure
      effective patient exposure to the drug.

PMID- 22147078
TI  - Thermal stabilization of thin gold nanowires by surfactant-coating: a molecular
      dynamics study.
AB  - The thermal stabilization of thin gold nanowires with a diameter of about 2 nm by
      surfactants is investigated by means of classical molecular dynamics simulations.
      While the well-known melting point depression leads to a much lower melting of
      gold nanowires compared to bulk gold, coating the nanowires with surfactants can
      reverse this, given that the attractive interaction between surfactant molecules
      and gold atoms lies beyond a certain threshold. It is found that the melting
      process of coated nanowires is dominated by surface instability patterns, whereas
      the melting behaviour of gold nanowires in a vacuum is dominated by the greater
      mobility of atoms with lower coordination numbers that are located at edges and
      corners. The suppression of the melting by surfactants is explained by the
      isotropic pressure acting on the gold surface (due to the attractive interaction)
      which successfully suppresses large-amplitude thermal motions of the gold atoms.

PMID- 22147079
TI  - Locoregional recurrence after breast cancer surgery: a systematic review by
      receptor phenotype.
AB  - Molecular subtyping confirms that breast cancer comprises at least four
      genetically distinct entities based on the expression of specific genes including
      estrogen receptor (ER), progesterone receptor (PR), and HER2/neu receptor. The
      quantitative influence of subtype on ipsilateral locoregional recurrence (LRR) is
      unknown. The aim of this study was to systematically appraise the influence of
      breast cancer subtype on LRR following breast conserving therapy (BCT) and
      mastectomy. A comprehensive search for studies examining outcomes after BCT
      and/or mastectomy according to breast cancer subtype was performed using Medline
      and cross-referencing available data. Reviews of each study were conducted and
      data extracted to perform meta-analysis. Primary outcome was LRR related to
      breast cancer subtype. A total of 12,592 breast cancer patients who underwent
      either BCT (n = 7,174) or mastectomy (n = 5,418) were identified from 15 studies.
      Patients with luminal subtype tumors (ER/PR +ve) had a lower risk of LRR than
      both triple-negative (RR 0.38; 95% CI 0.23-0.61); and HER2/neu-overexpressing (RR
      0.34; 95% CI 0.26-0.45) tumors following BCT. Luminal tumors were also less
      likely to develop LRR than HER2/neu-overexpressing (OR 0.69; 95% CI 0.54-0.89) or
      triple-negative tumors (OR 0.61; 95% CI 0.46-0.79) after mastectomy. HER2/neu
      overexpressing tumors have increased risk of LRR compared to triple-negative
      tumors (RR 1.44; 95% CI 1.06-1.95) following BCT but there was no difference in
      LRR between HER2/neu-overexpressing and triple-negative tumors following
      mastectomy (RR 0.91; 95% CI 0.68-1.22). Luminal tumors exhibit the lowest rates
      of LRR. Patients with triple-negative and HER2/neu-overexpressing breast tumors
      are at increased risk of developing LRR following BCT or mastectomy. Breast
      cancer subtype should be taken into account when considering local control and
      identifies those at increased risk of LRR, who may benefit from more aggressive
      local treatment.

PMID- 22147080
TI  - Evaluating breast cancer risk projections for Hispanic women.
AB  - For Hispanic women, the Breast Cancer Risk Assessment Tool (BCRAT; "Gail Model")
      combines 1990-1996 breast cancer incidence for Hispanic women with relative risks
      for breast cancer risk factors from non-Hispanic white (NHW) women. BCRAT risk
      projections have never been comprehensively evaluated for Hispanic women. We
      compared the relative risks and calibration of BCRAT risk projections for 6,353
      Hispanic to 128,976 NHW postmenopausal participants aged 50 and older in the
      Women's Health Initiative (WHI). Calibration was assessed by the ratio of the
      number of breast cancers observed with that expected by the BCRAT (O/E). We re
      evaluated calibration for an updated BCRAT that combined BCRAT relative risks
      with 1993-2007 breast cancer incidence that is contemporaneous with the WHI. Cox
      regression was used to estimate relative risks. Discriminatory accuracy was
      assessed using the concordance statistic (AUC). In the WHI Main Study, the BCRAT
      underestimated the number of breast cancers by 18% in both Hispanics (O/E = 1.18,
      P = 0.06) and NHWs (O/E = 1.18, P < 0.001). Updating the BCRAT improved
      calibration for Hispanic women (O/E = 1.08, P = 0.4) and NHW women (O/E = 0.98, P
      = 0.2). For Hispanic women, relative risks for number of breast biopsies (1.71
      vs. 1.27, P = 0.03) and age at first birth (0.97 vs. 1.24, P = 0.02) differed
      between the WHI and BCRAT. The AUC was higher for Hispanic women than NHW women
      (0.63 vs. 0.58, P = 0.03). Updating the BCRAT with contemporaneous breast cancer
      incidence rates improved calibration in the WHI. The modest discriminatory
      accuracy of the BCRAT for Hispanic women might improve by using risk factor
      relative risks specific to Hispanic women.

PMID- 22147081
TI  - GPER mediates the Egr-1 expression induced by 17beta-estradiol and 4
      hydroxitamoxifen in breast and endometrial cancer cells.
AB  - Early growth response-1 (Egr-1) is an immediate early gene involved in relevant
      biological events including the proliferation of diverse types of cell tumors. In
      a microarray analysis performed in breast cancer cells, 17beta-estradiol (E2) and
      the estrogen receptor antagonist 4-hydroxitamoxifen (OHT) up-regulated Egr-1
      through the G protein-coupled receptor named GPR30/GPER. Hence, in this study, we
      aimed to provide evidence regarding the ability of E2, OHT and the selective GPER
      ligand G-1 to regulate Egr-1 expression and function through the GPER/EGFR/ERK
      transduction pathway in both Ishikawa (endometrial) and SkBr3 (breast) cancer
      cells. Interestingly, we demonstrate that Egr-1 is involved in the transcription
      of genes regulating cell proliferation like CTGF and cyclin D1 and required for
      the proliferative effects induced by E2, OHT, and G-1 in both Ishikawa and SkBr3
      cells. In addition, we show that GPER mediates the expression of Egr-1 also in
      carcinoma-associated fibroblasts (CAFs). Our data suggest that Egr-1 may
      represent an important mediator of the biological effects induced by E2 and OHT
      through GPER/EGFR/ERK signaling in breast and endometrial cancer cells. The
      results obtained in CAFs provide further evidence regarding the potential role
      exerted by the GPER-dependent Egr-1 up-regulation in tumor development and
      progression. Therefore, Egr-1 may be included among the bio-markers of estrogen
      and antiestrogen actions and may be considered as a further therapeutic target in
      both breast and endometrial tumors.

PMID- 22147082
TI  - Occurrence of perfluoroalkyl substances in fish and water from the Svitava and
      Svratka rivers, Czech Republic.
AB  - Perfluoroalkyl substances (PFHxS, FHUEA, PFOA, PFOS, FOSA, N-methyl FOSA and
      PFNA) from seven sites on the Svitava and Svratka rivers in the Brno conurbation
      (Czech Republic) were determined in fish blood plasma and water. Concentrations
      of PFHxS, FHUEA, FOSA, and N-methyl FOSA were below detection limits. Major
      compound in fish blood was PFOS (38.9-57.8 ng mL(-1)), followed by PFNA and PFOA.
      In water, the major compound detected was PFOA (1.7-178.0 ng mL(-1)), followed by
      PFOS and PFNA. A significant (p < 0.05) correlation for PFOA concentration in
      blood plasma and water was found (r = 0.74).

PMID- 22147083
TI  - Dissipation of flubendiamide in/on okra [Abelmoschus esculenta (L.) Moench]
      fruits.
AB  - A field experiment was undertaken at Indian Agricultural Research Institute, New
      Delhi during kharif (rainy season) in the year 2010 to evaluate the residue
      persistence of flubendiamide in/on okra fruits following foliar application of
      Belt 39.35% SC formulation at 24 (standard dose) and 48 (double dose) g a.i. ha(
      1). After HPLC analysis study revealed that residues of flubendiamide in/on okra
      persisted till 5th and 7th day after the last spray at standard and double dose,
      respectively. The residues of flubendiamide were reported as parent compound, and
      des-iodo flubendiamide, a metabolite (photo product) of flubendiamide, was not
      detected in/on okra at any time during the study period. The initial deposits of
      0.28 and 0.53 MUg g(-1) in/on okra fruits reached below determination level of
      0.01 MUg g(-1) on the 7th and 10th day at standard and double dose, respectively.
      The half life of flubendiamide in/on okra fruits ranged from 4.7 to 5.1 days at
      standard and double dose, respectively. Soil sample collected from the treated
      field on the 15th day after the last spray revealed residues of flubendiamide or
      its metabolite below determination level (0.01 MUg g(-1)) at single and double
      dose.

PMID- 22147084
TI  - Mercury contamination in humans in Upper Maroni, French Guiana between 2004 and
      2009.
AB  - We measured hair mercury concentration in Amerindians between 2004 and 2009 in
      Upper Maroni, French Guiana. Hair samples were collected from 387 residents
      (males: 153, females: 234). Average hair mercury concentration was high (males:
      9.4 ppm, females: 9.9 ppm). We examined fish consumption by 37 residents. There
      was a significant correlation between hair mercury concentration and fish
      consumption. We also measured mercury concentration in polluted fish in upper
      reaches of the Maroni River. Muscle mercury concentrations were high in the fish.
      These results indicate that current high hair mercury concentrations in
      Amerindians remain linked to fish consumption.

PMID- 22147086
TI  - Breaking difficult news in a cross-cultural setting: a qualitative study about
      Latina mothers of children with down syndrome.
AB  - Giving difficult news to patients represents a common dilemma for health care
      professionals. Based on three decades of research, various authors have proposed
      guidelines outlining the ideal setting, delivery, and timing. Existing
      publications focus on patients of European descent and may not be applicable in
      cross-cultural settings. We explored perceptions of Spanish-speaking mothers who
      have a child with Down syndrome and how they preferred to receive the news of
      their child's diagnosis. We conducted semi-structured qualitative interviews (n =
      14), which were coded and analyzed by thematic networks to identify common
      themes. Six significant themes emerged: Cultural Belief System, Communication,
      Support/Lack of Support, Feelings Engendered, Medical Issues, and Medical System.
      One overarching theme of mother-child bonding encompassed all sub-themes. The
      mothers desired the news in a more positive, balanced light and with more
      complete explanations about the condition. Mothers felt excluded from the
      diagnostic process and wanted to be better informed about the need for diagnostic
      studies. Participants used religious beliefs to explain the reason for their
      child's condition. Many factors influenced Latina mothers' ability to bond
      initially with their children with Down syndrome. Ideally, these factors should
      be acknowledged during informing interviews to assist Latino families in
      adjustment.

PMID- 22147087
TI  - Countertransference in the genetic counseling setting: one counselor's personal
      journey.

PMID- 22147088
TI  - Taking advantage of a unique opportunity: a genetic counseling fellowship in
      lysosomal storage disorders.

PMID- 22147089
TI  - Changing my perspective: what my husband's cancer taught me about being a genetic
      counselor.

PMID- 22147090
TI  - [Levothyroxine and the problem of interchangeability of drugs with narrow
      therapeutic index].
AB  - The exchange of a prescribed drug by other similar, by generic products and even
      by custom products has become common practice in our country, often ignoring
      basic tenets of bioequivalence, interchangeability, stability and characteristics
      of the pharmaceutical compounds. In the case of drugs of narrow therapeutic
      index, such as levothyroxine, these problems are intensified, putting the
      effectiveness of treatment and patient health at serious risk. We review the
      pertinent legislation, emphasizing the characteristics of levothyroxine and
      adverse effects that limit the interchangeability of the compound.

PMID- 22147091
TI  - [Gestational diabetes management: a multidisciplinary treatment algorithm].
AB  - Effective treatment of gestational diabetes is important as an attempt to avoid
      unfavorable maternal and fetal outcomes. The objective of this paper is to
      describe the available therapies to optimize gestational diabetes treatment and
      to suggest a multidisciplinary approach algorithm. Nutrition therapy is the first
      option for the majority of these pregnancies; light to moderate physical activity
      is recommended in the absence of obstetrical contraindications. Medical treatment
      is recommended if glycemic control is not achieved or if excessive fetal growth
      is detected by ultrasound. Insulin is the standard treatment although oral
      antidiabetic drugs have recently been considered an effective and safe option.
      The monitoring of gestational diabetes treatment includes capillary glucose
      measurements and evaluation of fetal abdominal circumference by ultrasound
      performed around the 28th gestational week.

PMID- 22147092
TI  - ADIPOQ and adiponectin: the common ground of hyperglycemia and coronary artery
      disease?
AB  - Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to
      explain part of the interaction between obesity, insulin resistance, type 2
      diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role
      that adiponectin and ADIPOQ variants might play in the modulation of CAD,
      especially in the occurrence of hyperglycemia. Recent evidence suggests that
      total and high molecular weight (HMW) adiponectin levels are apparent markers of
      better cardiovascular prognosis in patients with low risk of CAD. However, in
      subjects with established or high risk of CAD, these levels are associated with
      poorer prognosis. We also provide recent evidences relating to the genetic
      control of total and HMW adiponectin levels, especially evidence regarding
      ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms
      in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia,
      and that these associations seem to be independent from each other, even if
      adiponectin levels are partly dependent on ADIPOQ.

PMID- 22147093
TI  - Serum and salivary cortisol in the diagnosis of adrenal insufficiency and as a
      predictor of the outcome in patients with severe sepsis.
AB  - OBJECTIVES: To compare salivary with serum total cortisol in patients with severe
      sepsis, postoperative patients and healthy controls. MATERIALS AND METHODS: Serum
      total cortisol was determined by chemiluminescence immunoassay; salivary cortisol
      was determined by enzyme immunoassay. RESULTS: In patients with severe sepsis,
      median concentration of salivary cortisol was 14.0 and 2.6 higher than that of
      postoperative patients and healthy subjects. In postoperative patients, salivary
      cortisol was 5.4 times higher than in control patients. Serum total cortisol was
      also higher in patients with severe sepsis than in controls and postoperative
      patients. This increment, however, was much lower (2.33 and 1.64, respectively).
      Patients with a salivary cortisol greater than 7.2 ug/dL had a mortality rate of
      80%, a statistically significant result when compared with the group with lower
      cortisol levels (Z = 2.38 and p < 0.05). CONCLUSIONS: Salivary cortisol in
      critically ill patients may be a better laboratory indicator of cortisol levels
      than serum total cortisol.

PMID- 22147094
TI  - Impact of subclinical hypothyroidism treatment in systolic and diastolic cardiac
      function.
AB  - OBJECTIVE: To evaluate the effects of levothyroxine (L-T4) replacement in
      echocardiographic parameters of middle-aged women with subclinical hypothyroidism
      (SH). SUBJECTS AND METHODS: This was a randomized, double-blind, placebo
      controlled study. Echocardiographic evaluation was carried out at baseline and
      one year after restoration of euthyroidism. Thirty-three women with SH were
      assigned to one of two groups (L-T4 or placebo). RESULTS: The two groups had
      similar basal characteristics. There was a significant deterioration of left
      ventricular Tei index after one year of placebo use, which differed from the
      effect of L-T4 replacement (+0.086 +/- 0.092 vs. -0.014 +/- 0.012; p = 0.047).
      There was also a slight reduction in cardiac output and cardiac index with
      placebo use, which was not different from L-T4 effect. CONCLUSION: Results
      suggest a positive impact of L-T4 replacement in cardiac function of middle-aged
      women with SH.

PMID- 22147095
TI  - Hypertension-related factors in patients with active and inactive acromegaly.
AB  - INTRODUCTION: There are several complications of the cardiovascular system caused
      by acromegaly, especially hypertension. OBJECTIVES: To evaluate hypertension
      characteristics in patients with cured/controlled acromegaly and with the active
      disease. PATIENTS AND METHODS: Cross-sectional study of the follow-up of forty
      four patients with acromegaly submitted to clinical evaluation, laboratory tests
      and cardiac ultrasound. Patients with cured and controlled disease were evaluated
      as one group, and individuals with active disease as second one. RESULTS: Forty
      seven percent of the patients had active acromegaly, and these patients were
      younger and had lower blood pressure levels than subjects with controlled/cured
      disease. Hypertension was detected in 50% of patients. Subjects with active
      disease showed a positive correlation between IGF-1 and systolic and diastolic
      blood pressure levels (r = 0.48, p = 0.03; and r = 0.42, p = 0.07, respectively),
      and a positive correlation between IGF-1 and urinary albumin excretion (UAE)
      rates. In patients with active disease, IGF-1 was a predictor of systolic blood
      pressure, although it was not independent of UAE rate. For individuals with
      cured/controlled disease, waist circumference and triglycerides were the
      predictors associated with systolic and diastolic blood pressure. CONCLUSIONS:
      Blood pressure (BP) levels in patients with active acromegaly dependent of the GH
      excess. However, once thedisease becomes controlled and IGF-1 levels decrease,
      their blood pressure levels are depend on the other cardiovascular riskfactors
      [corrected].

PMID- 22147096
TI  - Subclinical hypothyroidism and risk to carotid atherosclerosis.
AB  - OBJECTIVE: The aim of this study was to assess whether subclinical hypothyroidism
      (SCH) is associated with carotid atherosclerosis, as well as dyslipidemia, and
      arterial hypertension. SUBJECTS AND METHODS: The study included 69 consecutive
      patients with newly diagnosed SCH, and 30 matched healthy controls. Body mass
      index (BMI), TSH, fT4, antibodies to thyroid peroxidase (TPOabs), lipids, blood
      pressure, mean and maximum carotid intima-media thickness (CIMT) were determined
      in all participants. RESULTS: Mean values of CIMT, triglycerides, and total
      cholesterol/HDL-C ratio were significantly different in SCH patients versus
      matched controls. Linear multiple regression analysis demonstrated that TSH,
      diastolic blood pressure and triglycerides were independent predictors of mean
      CIMT, fT4 for maximum CIMT; and that TSH, fT4, age, and total cholesterol/HDL-C
      ratio were independent predictors of the presence of carotid plaques. CONCLUSION:
      Our data revealed that SCH is associated with increase in CIMT and presence of
      carotid plaques, independent of classical risk factors for atherosclerosis.

PMID- 22147097
TI  - Panhypopituitarism due to Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is a multi-system necrotizing granulomatous
      vasculitis which classically affects the upper respiratory tract, lungs and
      kidneys. Pituitary participation has been described in 24 patients in the
      literature to date. The aim of this article is to report a case of pituitary
      involvement in WG, and to present a literature review on this association. We
      present a female patient with WG who evolved with central diabetes insipidus
      (CDI), panhypopituitarism, and mild hyperprolactinemia. MRI showed an
      infiltrative pattern. Pituitary involvement has been reported in around 1% of
      patients with WG, mostly in women. It is represented by CDI and hypopituitarism.
      MRI generally shows pituitary enlargement, stalk thickening and loss of
      hyperintensity of the neurohypophysis. Permanent endocrine therapy is generally
      needed. WG should be considered in cases of CDI and hypopituitarism, essentially
      if a vasculitis is suspected and more common sellar disorders have been ruled
      out.

PMID- 22147098
TI  - Importance of (99)mTc-sestaMIBI thyroid scan in a case of amiodarone-induced
      thyrotoxicosis.
AB  - Amiodarone (AM)-induced thyrotoxicosis (AIT) is a condition with uncertainties
      from the diagnostic and therapeutic standpoints. A 54-year old male was referred
      to the hospital due to thyrotoxicosis. He had history of atrial fibrillation
      medicated with AM. No history of pre-existing thyroid disease was present,
      thyroid palpation revealed no goiter, and there were no signs of Graves'
      ophthalmopathy. Thyroid autoantibodies and thyroid-stimulating hormone receptor
      antibodies (TRABs) were negative. Thyroid and Doppler ultrasounds were normal.
      99mTc-sestaMIBI thyroid scan (STS) showed uptake with rapid washout. AM therapy
      was discontinued, and combined therapy was started. After a long course of
      glucocorticoid and thionamides, the patient became euthyroid. It is necessary to
      distinguish between the types of AIT to decide whether or not continue AM
      treatment; after that, the appropriate therapy should be selected. STS was very
      important in the diagnosis of the type of AIT.

PMID- 22147099
TI  - Incidental finding of ovarian teratoma on post-therapy scan for papillary thyroid
      cancer and impact of SPECT/CT imaging.
AB  - A 41-year old woman post thyroidectomy and neck dissection is presented in this
      case. She initially presented goiter and an enlarged cervical lymph node. She had
      no family history of cancer or radiation therapy. She had total thyroidectomy and
      found to have papillary thyroid cancer (T4N1M0). Histopathology report revealed
      multifocal classical papillary thyroid carcinoma with lympho-vascular invasion,
      extra-thyroidal extension, and positive lymph nodes. She was treated with 6.5
      Gigabecquerel (GBq) of 131Iodine. Whole-body scan showed uptake in the neck and
      large focus in the left lower abdomen. Single-photon emission computed tomography
      SPECT/CT demonstrated a round shaped mass in the left pelvis. Pathology revealed
      cystic teratoma with benign thyroid tissue (struma ovarii), and no malignancy.
      Two months later, she had the second treatment with 5.5 GBq 131Iodine. Her follow
      up stimulated and non-stimulated thyroglobulin levels were significantly lower,
      and there was no abnormal uptake in the follow-up scan.

PMID- 22147100
TI  - Postglucose growth hormone nadir and insulin-like growth factor-1 in naive-active
      acromegalic patients: do these parameters always correlate?

PMID- 22147101
TI  - Review of risk assessment instruments for juvenile sex offenders: what is next?
AB  - Risk assessment is considered to be a key element in the prevention of recidivism
      among juvenile sex offenders (JSOs), often by imposing long-term consequences
      based on that assessment. The authors reviewed the literature on the predictive
      accuracy of six well-known risk assessment instruments used to appraise risk
      among JSOs: the Juvenile Sex Offender Assessment Protocol-II (J-SOAP-II),
      Juvenile Sexual Offence Recidivism Risk Assessment Tool-II (J-SORRAT-II),
      Estimate of Risk of Adolescent Sexual Offence Recidivism (ERASOR), Juvenile Risk
      Assessment Scale (JRAS), Structured Assessment of Violent Risk in Youth (SAVRY),
      and Hare Psychopathy Checklist:Youth Version (PCL:YV). Through a systematic
      search, 19 studies were reviewed. Studies showed differences in the predictive
      accuracies for general, violent, and sexual recidivism, and none of the
      instruments showed unequivocal positive results in predicting future offending.
      Not unexpectedly, the accuracy of the SAVRY and PCL:YV appeared to be weaker for
      sexual recidivism compared with specialized tools such as the J-SOAP-II or the
      ERASOR. Because of the rapid development of juveniles, it is questionable to
      impose long-term restrictions based on a risk assessment only. New challenges in
      improving risk assessment are discussed.

PMID- 22147102
TI  - Modeling optimal age-specific vaccination strategies against pandemic influenza.
AB  - In the context of pandemic influenza, the prompt and effective implementation of
      control measures is of great concern for public health officials around the
      world. In particular, the role of vaccination should be considered as part of any
      pandemic preparedness plan. The timely production and efficient distribution of
      pandemic influenza vaccines are important factors to consider in mitigating the
      morbidity and mortality impact of an influenza pandemic, particularly for those
      individuals at highest risk of developing severe disease. In this paper, we use a
      mathematical model that incorporates age-structured transmission dynamics of
      influenza to evaluate optimal vaccination strategies in the epidemiological
      context of the Spring 2009 A (H1N1) pandemic in Mexico. We extend previous work
      on age-specific vaccination strategies to time-dependent optimal vaccination
      policies by solving an optimal control problem with the aim of minimizing the
      number of infected individuals over the course of a single pandemic wave. Optimal
      vaccination policies are computed and analyzed under different vaccination
      coverages (21%-77%) and different transmissibility levels ([Formula: see text] in
      the range of 1.8-3). The results suggest that the optimal vaccination can be
      achieved by allocating most vaccines to young adults (20-39 yr) followed by
      school age children (6-12 yr) when the vaccination coverage does not exceed 30%.
      For higher [Formula: see text] levels ([Formula: see text]), or a time delay in
      the implementation of vaccination (>90 days), a quick and substantial decrease in
      the pool of susceptibles would require the implementation of an intensive
      vaccination protocol within a shorter period of time. Our results indicate that
      optimal age-specific vaccination rates are significantly associated with
      [Formula: see text], the amount of vaccines available and the timing of
      vaccination.

PMID- 22147103
TI  - A model of neuregulin control of NMDA receptors on synaptic spines.
AB  - Neuregulin (Nrg) through its receptor ErbB4 modulates the activity of the N
      Methyl-D-Aspartate (NMDA) receptor (NMDAR) at synapses. As modification of this
      pathway has been implicated in schizophrenia, it is of great interest to define
      it in precise quantitative terms. Kinetic models of the epidermal growth factor
      (EGF)/ErbB receptor signalling pathway describing activation, desensitization,
      and tyrosine phosphorylation of EGFR/ErbB followed by binding and activation of
      Src family kinases that is subsequently followed by phosphorylation of target
      proteins are available. We have adapted these to give a kinetic description of
      NMDAR modulation by Nrg that recapitulates the observed kinetics of
      autophosphorylation of the ErbB dimer as well as the modulation of the NMDAR by
      Src kinase, according to whether the kinases are activated or deactivated. This
      quantitative description of the Nrg/NMDAR pathway provides a model for
      experimental elucidation of what goes awry in animal models of schizophrenia.

PMID- 22147104
TI  - Electromigration dispersion in capillary electrophoresis.
AB  - In a previous paper (Ghosal and Chen in Bull. Math. Biol. 72:2047, 2010), it was
      shown that the evolution of the solute concentration in capillary electrophoresis
      is described by a nonlinear wave equation that reduced to Burger's equation if
      the nonlinearity was weak. It was assumed that only strong electrolytes (fully
      dissociated) were present. In the present paper, it is shown that the same
      governing equation also describes the situation where the electrolytic buffer
      consists of a single weak acid (or base). A simple approximate formula is derived
      for the dimensionless peak variance which is shown to agree well with published
      experimental data.

PMID- 22147105
TI  - Biobutanol production from rice bran and de-oiled rice bran by Clostridium
      saccharoperbutylacetonicum N1-4.
AB  - Rice bran (RB) and de-oiled rice bran (DRB) have been treated and used as the
      carbon source in acetone-butanol-ethanol (ABE) production using Clostridium
      saccharoperbutylacetonicum N1-4. The results showed that pretreated DRB produced
      more ABE than pretreated RB. Dilute sulfuric acid was the most suitable treatment
      method among the various pretreatment methods that were applied. The highest ABE
      obtained was 12.13 g/L, including 7.72 g/L of biobutanol, from sulfuric acid. The
      enzymatic hydrolysate of DRB (ESADRB), when treated with XAD-4 resin, resulted in
      an ABE productivity and yield of 0.1 g/L h and 0.44 g/g, respectively. The
      results also showed that the choice of pretreatment method for RB and DRB is an
      important factor in butanol production.

PMID- 22147106
TI  - Characterisation of non-calcified coronary plaque by 16-slice multidetector
      computed tomography: comparison with histopathological specimens obtained by
      directional coronary atherectomy.
AB  - The efficacy of multidetector computed tomography (MDCT) for assessing coronary
      plaque composition has not been fully elucidated by comparison with histological
      findings. This study investigated the efficacy and limitations of CT density for
      identifying non-calcified lipid-rich plaque compared with histopathological
      findings. We studied 41 target lesions treated by directional coronary
      atherectomy in 41 patients with coronary artery disease who had non-calcified
      plaques detected by 16-slice MDCT before intervention. The lesions were
      histopathologically classified as lipid-rich or non-lipid-rich plaques, as well
      as according to the presence or absence of histopathological microcalcification.
      The mean CT density was determined in 5 regions of interest per slice and
      compared among the groups. The optimum cut-off value for identifying lipid-rich
      plaque was determined by receiver operating characteristic (ROC) analysis using
      histological findings for reference. Eighteen lesions were histopathologically
      classified as lipid-rich (5 with microcalcification and 13 without it) and 23
      lesions were non-lipid-rich (8 with microcalcification and 15 without it). The
      mean CT density was significantly lower for lipid-rich plaque without
      microcalcification compared with other plaque types (P = 0.0001). ROC analysis
      revealed that the optimum cut-off value for distinguishing lipid-rich from non
      lipid-rich plaque without microcalcification was 50 HU (sensitivity: 92.3%;
      specificity: 93.3%). Histopathological microcalcification had a marked influence
      on the plaque CT density. Sixteen-slice MDCT can identify lipid-rich plaque by a
      low CT density. However, high CT density dose not exclude the possibility of
      lipid-rich plaque, and combined morphological assessment is necessary to
      differentiate plaque components.

PMID- 22147107
TI  - Combined anatomical and functional imaging using coronary CT angiography and
      myocardial perfusion SPECT in symptomatic adults with abnormal origin of a
      coronary artery.
AB  - There has been a lack of standardized workup guidelines for patients with
      congenital abnormal origin of a coronary artery from the opposite sinus (ACAOS).
      We aimed to evaluate the use of cardiac hybrid imaging using multi-detector row
      CT (MDCT) for coronary CT angiography (Coronary CTA) and stress-rest myocardial
      perfusion SPECT (MPS) for comprehensive diagnosis of symptomatic adult patients
      with ACAOS. Seventeen symptomatic patients (12 men; 54 +/- 13 years) presenting
      with ACAOS underwent coronary CTA and MPS. Imaging data were analyzed by
      conventional means, and with additional use of 3D image fusion to allocate stress
      induced perfusion defects (PD) to their supplying coronary arteries. An anomalous
      RCA arose from the left anterior sinus in eight patients, an abnormal origin from
      the right sinus was detected in nine patients (5 left coronary arteries, LCA and
      4 LCx). Five of the 17 patients (29%) demonstrated a reversible PD in MPS. There
      was no correlation between the anatomical variants of ACAOS and the presence of
      myocardial ischemia. Image fusion enabled the allocation of reversible PD to the
      anomalous vessel in three patients (two cases in the RCA and the other in the LCA
      territory); PD in two patients were allocated to the territory of artery giving
      rise to the anomalies, rather than the anomalies themselves. In a small cohort of
      adult symptomatic patients with ACAOS anomaly there was no relation found between
      the specific anatomical variant and the appearance of stress induced myocardial
      ischemia using cardiac hybrid imaging.

PMID- 22147108
TI  - Identification of forty cases with alkaptonuria in one village in Jordan.
AB  - Alkaptonuria (AKU) is one of the four initially identified inborn errors of
      metabolism. The prevalence of AKU is unknown in Jordan. Therefore, a research
      project was started in April 2009 at the Faculty of Medicine/Mutah University in
      southern Jordan. The aims of the project were to identify people with AKU, to
      screen all family members with history of AKU, and to increase the awareness
      about the disease among health care professionals and the community in southern
      Jordan. Targeted family screening method was used to identify patients with AKU.
      In this paper, we present preliminary results of screening 17 families with
      history of AKU in a single village in southern region of Jordan. Forty cases with
      AKU were identified in this village (age range, 1-60 years). Early cases with AKU
      were diagnosed through out this study, two-third of patients (n = 28) were under
      the age of thirty. Interestingly, nine cases with AKU were identified in one
      family. Our experience suggests that for the identification of cases with AKU
      where consanguinity is common, the focus for screening should be extended to all
      family members. The prevalence of AKU among Jordanian is likely to be greater
      than the prevalence rates worldwide due to high rates of consanguineous
      marriages. Further studies and effective screening programs are needed to detect
      undiagnosed cases of AKU, to provide genetic counseling, and ultimately to
      prevent the occurrence of new cases of AKU in Jordan.

PMID- 22147109
TI  - Comparison of qualitative and quantitative analysis of capillaroscopic findings
      in patients with rheumatic diseases.
AB  - No guidelines for the application of qualitative and quantitative analysis of the
      capillaroscopic examination in the rheumatologic practice exist. The aims of the
      study were to compare qualitative and quantitative analysis of key
      capillaroscopic parameters in patients with common rheumatic diseases and to
      assess the reproducibility of the qualitative evaluation of the capillaroscopic
      parameters, performed by two different investigators. Two hundred capillaroscopic
      images from 93 patients with different rheumatic diseases were analysed
      quantitatively and qualitatively by two different investigators. The distribution
      of the images according to the diagnosis and the microvascular abnormalities was
      as follows-group 1: 73 images from systemic sclerosis patients ("scleroderma"
      type pattern), group 2: 10 images from dermatomyositis ("scleroderma-like"
      pattern), group 3: 25 images from undifferentiated connective tissue disease and
      different forms of overlap (24 "scleroderma-like"), group 4: 26 images from
      systemic lupus erythematosus patients, group 5: 46 images from rheumatoid
      arthritis and group 6: 20 images from primary Raynaud's phenomenon patients. All
      the images were mixed and blindly presented to both investigators. For comparison
      of the quantitative and qualitative method, investigator 1 assessed presence of
      dilated, giant capillaries and avascular areas quantitatively by the available
      software programme and his estimates were compared with the results of
      investigator 2, who assessed the parameters qualitatively. In addition, the
      capillaroscopic images were evaluated qualitatively by the investigator 1 and 2
      for presence of dilated, giant capillaries, avascular areas and haemorrhages. The
      comparison of the quantitative and qualitative assessment of the two
      investigators demonstrated statistically significant difference between the two
      methods for the detection of dilated and giant capillaries (P < 0.05) but no
      significant difference regarding the detection of avascular areas (P > 0.05). As
      we further analysed the results for the capillaroscopic images, demonstrating a
      "scleroderma" and a "scleroderma-like" pattern (170/200), analogous results were
      found for the evaluated parameters. Among the 20 capillaroscopic images from
      patients with primary RP, the estimates for the absence of giant capillaries and
      avascular areas were equal in 100% (P > 0.05). Comparing the qualitative
      assessment of the two investigators, a statistically significant difference
      between estimates of the two investigators was found for the presence of dilated
      capillaries (P < 0.05), while for giant capillaries, avascular areas and
      haemorrhages the difference was not statistically significant (P > 0.05). The
      results of the study have shown that qualitative assessment of capillaroscopic
      parameters in patients with rheumatic diseases is an adequate method for the
      everyday rheumatologic practice, especially in cases with primary RP for
      exclusion presence of microangiopathy. No significant difference between
      qualitative and quantitative methods of assessment was found for the detection of
      avascular areas. However, the quantitative analysis is more precise especially
      for the detection of capillary dilation. A good reproducibility of the
      qualitative evaluation, performed by two different investigators was also found.

PMID- 22147110
TI  - Cardiovascular risk in patients with rheumatoid arthritis: assessment of several
      traditional risk parameters and a German risk score model.
AB  - The present cross-sectional data demonstrate cardiovascular (CV) risk in patients
      with rheumatoid arthritis (RA). The cross-sectional data were part of an
      interventional trial that included 100 patients with defined RA. Traditional CV
      risk parameters and risk score calculation for the German population were used to
      assess the CV risk profile in the collective given. Proatherogenic lipid profile
      characterised by increased total cholesterol (>= 5.2 mmol/l) and LDL cholesterol
      (>= 3.5 mmol/l) levels was measured in 85 and 66%, respectively, of the study
      population. Elevated concentrations of homocysteine (>= 10 MUmol/l) were reached
      by 67%. The prevalence of patients at high CV risk was 12% and increased up to
      42% after using a multiplication factor of 1.5. No association was seen between
      the CV risk SCORE and DAS 28 or disease duration. RA patients in this study
      showed a proatherogenic risk profile with regard to the CV risk factors
      evaluated. The calculation of a 10-year risk using German risk charts might have
      led to an overall underestimation of the mean CV risk. Cardiovascular co
      morbidity in RA patients must be seen as a major prevention and treatment target
      and should be monitored adequately.

PMID- 22147111
TI  - Hepatitis B virus reactivation in a juvenile rheumatoid arthritis patient under
      treatment and its successful management: a complicated case.
AB  - Juvenile rheumatoid arthritis is a common chronic inflammatory disease in the
      childhood and it can differentiate rarely into spondiloarthropaties. It is one of
      the important causes of chronic pain and disability. Some of the drugs used for
      the treatment have immunosupressive activity. One of the serious side-effects of
      immunosupressive treatment is activation of opportunistic pathogens. Hepatitis B
      virus (HBV) is one of these pathogens, and the rate of carriers in the population
      is considerably high. It can cause liver damage and death if reactivated. Thus,
      the management of oppotunistic pathogens becomes a complex issue when treating
      rheumatic diseases with immunosupressive drugs. In this case report, we present a
      juvenile rheumatoid arthritis patient whose liver enzymes raised while he was
      under treatment and afterwards HBV reactivation was determined as the cause. When
      reactivation was detected, we started controlled antiviral therapy. We achieved
      successful clinical and laboratory results after adding biological agents to the
      treatment. Careful evaluation of the patients who have indication for
      immunosuppressive agents and regular follow-up in case of infection may be
      protective from severe morbidity and/or mortality.

PMID- 22147113
TI  - Comment on Legrand et al.: The role of renal hypoperfusion in development of
      renal microcirculatory dysfunction in endotoxemic rats.

PMID- 22147112
TI  - BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in
      mechanically ventilated patients with Gram-negative pneumonia.
AB  - PURPOSE: To conduct a multicenter, randomized, placebo-controlled, double-blind,
      phase II study of BAY41-6551 (NCT01004445), an investigational drug-device
      combination of amikacin, formulated for inhalation, and a proprietary Pulmonary
      Drug Delivery System, for the treatment of Gram-negative pneumonia in
      mechanically ventilated patients. METHODS: Sixty-nine mechanically ventilated
      patients with Gram-negative pneumonia, a clinical pulmonary infection score >=6,
      at risk for multidrug-resistant organisms, were randomized to BAY41-6551 400 mg
      every 12 h (q12h), 400 mg every 24 h (q24h) with aerosol placebo, or placebo q12h
      for 7-14 days, plus standard intravenous antibiotics. The combined primary
      endpoint was a tracheal aspirate amikacin maximum concentration >=6,400 MUg/mL
      (25 * 256 MUg/mL reference minimum inhibitory concentration) and a ratio of area
      under the aspirate concentration-time curve (0-24 h) to minimum inhibitory
      concentration >=100 on day 1. RESULTS: The primary endpoint was achieved in 50%
      (6/12) and 16.7% (3/18) of patients in the q12h and q24h groups, respectively.
      Clinical cure rates, in the 48 patients getting >=7 days of therapy, were 93.8%
      (15/16), 75.0% (12/16), and 87.5% (14/16) in the q12h, q24h, and placebo groups,
      respectively (p = 0.467). By the end of aerosol therapy, the mean number of
      antibiotics per patient per day was 0.9 in the q12h, 1.3 in the q24h, and 1.9 in
      the placebo groups, respectively (p = 0.02 for difference between groups). BAY41
      6551 was well tolerated and attributed to two adverse events in one patient (mild
      bronchospasm). CONCLUSIONS: BAY41-6551 400 mg q12h warrants further clinical
      evaluation.

PMID- 22147115
TI  - Diffuse digestive bezoar: a rare and severe complication of enteral nutrition in
      the intensive care unit (ICU).

PMID- 22147117
TI  - Exciting new ECMO technology awaits compelling scientific evidence for widespread
      use in adults with respiratory failure.

PMID- 22147116
TI  - Contemporary extracorporeal membrane oxygenation for adult respiratory failure:
      life support in the new era.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used in clinical
      medicine for 40 years but remains controversial therapy, particularly in adult
      patients with severe respiratory failure. Over the last few years, there have
      been considerable advances in extracorporeal technology and clinical practice,
      ushering in a new era of ECMO. Many institutions adopted ECMO as rescue therapy
      during the recent H1N1 influenza pandemic, reigniting the controversy.
      DISCUSSION: Hollow-fibre oxygenators and Mendler-designed centrifugal pumps have
      replaced the old silicon oxygenators and roller pumps. The advantages of these
      novel systems and the principles that underlie their function are outlined.
      Advances in cannula technology allow greater ease of patient positioning, in some
      cases facilitating extubation and ambulation on ECMO. Improvements in ECMO
      circuitry have led to a reduction in heparin and blood product requirements, with
      consequently fewer complications. Greater understanding of severe acute
      respiratory distress syndrome has allowed clinicians to successfully support
      adults on ECMO for months at a time, as a bridge to either recovery or
      transplantation. CONCLUSIONS: ECMO is safer, cheaper, and simpler than in
      previous eras. Both circuit and patient can be cared for by a single trained
      nurse. Additional prospective studies of ECMO for adult respiratory failure are
      underway. Contemporary ECMO in awake, potentially ambulant patients to provide
      short-term support for those with acute, reversible respiratory failure and as a
      bridge to transplantation in those with irreversible respiratory failure is now
      ready for widespread evaluation.

PMID- 22147118
TI  - Controlled growth of carbon nanotube-graphene hybrid materials for flexible and
      transparent conductors and electron field emitters.
AB  - We report a versatile synthetic process based on rapid heating and cooling
      chemical vapor deposition for the growth of carbon nanotube (CNT)-graphene hybrid
      materials where the thickness of graphene and density of CNTs are properly
      controlled. Graphene films are demonstrated as an efficient barrier layer for
      preventing poisoning of iron nanoparticles, which catalyze the growth of CNTs on
      copper substrates. Based on this method, the opto-electronic and field emission
      properties of graphene integrated with CNTs can be remarkably tailored. A
      graphene film exhibits a sheet resistance of 2.15 kOmega sq(-1) with a
      transmittance of 85.6% (at 550 nm), while a CNT-graphene hybrid film shows an
      improved sheet resistance of 420 Omega sq(-1) with an optical transmittance of
      72.9%. Moreover, CNT-graphene films are demonstrated as effective electron field
      emitters with low turn-on and threshold electric fields of 2.9 and 3.3 V MUm(-1),
      respectively. The development of CNT-graphene films with a wide range of tunable
      properties presented in this study shows promising applications in flexible opto
      electronic, energy, and sensor devices.

PMID- 22147119
TI  - Gene expression profiles for genotoxic effects of silica-free and silica-coated
      cobalt ferrite nanoparticles.
AB  - Nanomaterials have been widely evaluated for potential use as efficient delivery
      carriers for cancer diagnosis and therapy. To translate these nanomaterials to
      the clinic, their safety needs to be verified, particularly in terms of
      genotoxicity and cytotoxicity. We investigated changes in gene expression
      profiles influenced by silica-coated cobalt ferrite magnetic-fluorescence
      nanoparticles and silica-free cobalt ferrite magnetic-core nanoparticles in vivo
      and in vitro. METHODS: (68)Ga-labeled cobalt ferrite nanoparticles produced by
      synthesis of 2-(p-isothio-cyanatobenzyl)-1,4,7-triazacyclonane-1,4,7-triacetic
      acid chelator were established after labeling efficiency had been validated
      through a thin-layer chromatography method. The expression of genes associated
      with the stress and toxicity pathways was verified by a commercially available
      polymerase chain reaction array kit. RESULTS: In comparison with magnetic
      fluorescence nanoparticles, magnetic-core nanoparticles revealed severe cytotoxic
      effects at various doses and treatment times as determined by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Whole-body small
      animal PET and biodistribution studies, including transmission electron
      microscope analysis, showed that tail-vein injection of magnetic-core or magnetic
      fluorescence nanoparticles exhibited substantial liver accumulation. Real-time
      polymerase chain reaction array using 52 genes related to cellular toxicity
      demonstrated that 17 genes from the magnetic-core-treated liver samples were
      significantly affected, mostly in relation to DNA damage or repair and to
      oxidative or metabolic stress. The magnetic-fluorescence-treated liver samples
      showed gene expression approximately 90% similar to that of untreated liver
      samples. CONCLUSION: We compared a variety of gene expression profiles in mice
      injected with magnetic-fluorescence or magnetic-core nanoparticles. This study of
      gene expression profiles affected by nanotoxicity provides critical information
      for the clinical use of silica-coated cobalt ferrite.

PMID- 22147120
TI  - Personality traits and educational identity formation in late adolescents:
      longitudinal associations and academic progress.
AB  - Changes in personality traits in late adolescence and young adulthood are
      believed to co-occur with changes in identity, but little research is available
      that supports this hypothesis. The present study addressed this relatively
      understudied area of research by examining longitudinal associations of Big Five
      personality traits (i.e., Neuroticism, Extraversion, Openness, Agreeableness, and
      Conscientiousness) with dimensions of identity formation (i.e., identification
      with commitment and exploration in depth) in the domain of education. For this
      purpose, we used four annual waves of longitudinal data on 485 Belgian late
      adolescents (87.4% female; mean age at T1 = 18.6 years) covering a 3-year period.
      Multivariate growth models revealed that changes in Big Five personality traits
      were related to changes in identification with commitment and exploration in
      depth. Cross-lagged panel models uncovered that, except for Openness, all Big
      Five traits predicted educational identity dimensions. Educational identity
      dimensions only predicted Neuroticism. In addition, adolescents with higher
      levels on the personality trait of Conscientiousness faced fewer study delays. In
      sum, the present study adds to the growing literature that explores the
      antecedents, correlates, and consequences of personality trait development by
      uncovering the interplay of personality traits, educational identity dimensions,
      and academic progress in late adolescents.

PMID- 22147121
TI  - Soluble VEGF receptor 1 promotes endothelial injury in children and adolescents
      with lupus nephritis.
AB  - BACKGROUND: Endothelial cell injury plays a key role in the pathogenesis of lupus
      nephritis (LN) and atherosclerosis. The aim of this study was to identify factors
      involved in the process of endothelial damage in children and adolescents with
      LN. METHODS: We evaluated the relationship between plasma vascular endothelial
      growth factor (VEGF), its soluble receptors sVEGFR-1 and sVEGFR-2 and markers of
      endothelial inflammation and injury (angiopoietin-2 and thrombomodulin,
      respectively) in 23 children and adolescents with LN (active LN, n = 14; inactive
      LN, n = 9; mean age 15 years) and 20 healthy controls (HC; mean age 12 years).
      RESULTS: VEGF, sVEGFR-1, angiopoietin-2 and thrombomodulin levels were
      significantly higher in children and adolescents with active LN than in patients
      in remission or HC. In active LN, however, VEGF was inversely related to sVEGFR-1
      (r = -0.802, p < 0.001), angiopoietin-2 (r = -0.684, p = 0.007) and
      thrombomodulin (r = -0.697, p = 0.006). There was a significant positive
      correlation between sVEGFR-1 and thrombomodulin (r = 0.814, p < 0.0001), but
      sVEGFR-2 did not significantly differ between the patient groups and did not
      correlate with thrombomodulin (r = 0.046, p = 0.833). CONCLUSIONS: sVEGFR-1 may
      play an important role in promoting endothelial damage in children and
      adolescents with active LN and could possibly be used to monitor disease
      severity.

PMID- 22147124
TI  - Current issues on the understanding of locally advanced colorectal cancer.

PMID- 22147125
TI  - Clinical, endoscopic and histopathological profiles of parasitic duodenitis cases
      diagnosed by upper digestive endoscopy.
AB  - CONTEXT: Intestinal parasites induce detectable histopathological changes, which
      have been studied in groups with known diagnosis of parasitic disease. There is
      no available study with a larger base without previous diagnosis. OBJECTIVE: To
      describe clinical and histopathological findings of parasitosis diagnosed by
      endoscopic biopsy in patients submitted to upper digestive endoscopy. METHODS:
      Recorded biopsies archive at "Complexo Hospitalar Professor Edgar Santos" , a
      general teaching Hospital in the state of Bahia, Northeast Brazil, from January
      1995 to January 2009, were reviewed. One thousand ten duodenal biopsy reports
      were found. Reports positive for parasites had their specimens reviewed and
      photographed. All blocks of biopsy selected as case were retrieved and reviewed
      by an experienced pathologist. Clinical, laboratorial and endoscopic data were
      collected. RESULTS: Eleven biopsies showed parasites, including cases of
      Cryptosporidium sp. and Strongyloides stercoralis. Vomiting (91%), abdominal pain
      (78%), diarrhea (78%) and weight loss (78%) were usual symptoms. Seventy-five
      percent had duodenal mucosa changes on endoscopy, while 25% have no changes.
      Anemia and low serum albumin were important laboratorial data. HIV infection
      association was observed. Villus atrophy and reactive epithelium were usual in
      Strongyloides cases. CONCLUSIONS: No endoscopic or histopathologic finding was
      pathognomonic. One percent of duodenal endoscopic biopsies showed parasites.

PMID- 22147122
TI  - Updated report on comparative effectiveness of ACE inhibitors, ARBs, and direct
      renin inhibitors for patients with essential hypertension: much more data, little
      new information.
AB  - OBJECTIVES: A 2007 systematic review compared angiotensin-converting enzyme (ACE)
      inhibitors and angiotensin II receptor blockers (ARBs) in patients with
      hypertension. Direct renin inhibitors (DRIs) have since been introduced, and
      significant new research has been published. We sought to update and expand the
      2007 review. DATA SOURCES: We searched MEDLINE and EMBASE (through December 2010)
      and selected other sources for relevant English-language trials. STUDY
      ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included studies that
      directly compared ACE inhibitors, ARBs, and/or DRIs in at least 20 total adults
      with essential hypertension; had at least 12 weeks of follow-up; and reported at
      least one outcome of interest. Ninety-seven (97) studies (36 new since 2007)
      directly comparing ACE inhibitors versus ARBs and three studies directly
      comparing DRIs to ACE inhibitor inhibitors or ARBs were included. STUDY APPRAISAL
      AND SYNTHESIS METHODS: A standard protocol was used to extract data on study
      design, interventions, population characteristics, and outcomes; evaluate study
      quality; and summarize the evidence. RESULTS: In spite of substantial new
      evidence, none of the conclusions from the 2007 review changed. The level of
      evidence remains high for equivalence between ACE inhibitors and ARBs for blood
      pressure lowering and use as single antihypertensive agents, as well as for
      superiority of ARBs for short-term adverse events (primarily cough). However, the
      new evidence was insufficient on long-term cardiovascular outcomes, quality of
      life, progression of renal disease, medication adherence or persistence, rates of
      angioedema, and differences in key patient subgroups. LIMITATIONS: Included
      studies were limited by follow-up duration, protocol heterogeneity, and
      infrequent reporting on patient subgroups. CONCLUSIONS AND IMPLICATIONS OF KEY
      FINDINGS: Evidence does not support a meaningful difference between ACE
      inhibitors and ARBs for any outcome except medication side effects. Few, if any,
      of the questions that were not answered in the 2007 report have been addressed by
      the 36 new studies. Future research in this area should consider areas of
      uncertainty and be prioritized accordingly.

PMID- 22147126
TI  - New "introducer" PEG-gastropexy with T fasteners: a pilot study.
AB  - CONTEXT: Enteral feeding is indicated for patients unable to maintain appropriate
      oral intake, and percutaneous endoscopic gastrostomy (PEG) is the most adequate
      long-term enteral access. Peristomal infections are the most common complications
      of PEG, occurring in up to 8% of patients, despite the use of prophylactic
      antibiotics. The "introducer" PEG-gastropexy technique avoids PEG tube passage
      through the oral cavity, preventing microorganisms' dislodgment to the peristomal
      site. OBJECTIVES: To compare the incidence of peristomal wound infection at 7-day
      post-procedure after conventional "pull" technique versus a new "introducer" PEG
      gastropexy kit. Secondary outcomes included success rates, procedure time, and
      other complications. METHODS: Eighteen patients referred for PEG placement
      between June and December 2010 were randomly assigned to "pull" PEG with
      antibiotics or "introducer" PEG-gastropexy technique without antibiotics.
      RESULTS: Overall success rate for both methods was 100%, although mean procedure
      duration was higher in the "introducer" PEG-gastropexy group (12.6 versus 6.4
      minutes, P = 0.0166). Infection scores were slightly higher in patients who
      underwent "pull" PEG with antibiotics compared with "introducer" PEG-gastropexy
      without antibiotics (1.33 +/- 0.83 versus 0.75 +/- 0.67, P = 0.29). CONCLUSION:
      Although procedure duration was longer in the "introducer" PEG-gastropexy,
      infection scores were marginally higher in the "pull" PEG technique.

PMID- 22147127
TI  - Upper endoscopy versus endosonography in differential diagnosis of
      gastrointestinal bulging.
AB  - CONTEXT: The identification of a bulging covered by normal epithelium is a common
      finding during an upper gastrointestinal endoscopy. OBJECTIVE: To compare the
      endoscopic and endosonography findings in the differential diagnosis of the
      gastrointestinal bulging (subepithelial tumor or extrinsic compression). METHOD:
      Patients referred by endosonography with bulging of upper gastrointestinal tract
      were studied retrospectively. The size, location, consistency and presumptive
      diagnosis were recorded at time of endoscopy and endosonography. Endosonography
      guided fine-needle aspiration was proposed in case of uncertain diagnose to
      increase diagnostic sensitivity. RESULTS: One hundred seventy-six patients (93
      women) and mean age 62.5 years (10-87). One hundred fifty-three had subepithelial
      tumor and 23 had extrinsic compression as a final diagnosis. Endosonography had
      sensitivity, specificity and accuracy higher than those found by endoscopy for
      both diagnosis subepithelial tumor and extrinsic compression. Endoscopy and
      endosonography showed poor concordance (K = 0.13) for subepithelial tumor
      diagnosis and unsuitable agreement for diagnosis in extrinsic compression (K =
      0.01). The endosonography-guided fine-needle aspiration had sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      75%, 72.4%, 80.5%, 65.6% and 74%, respectively. CONCLUSION: Endoscopy has high
      sensitivity and low specificity for subepithelial tumor and both are low for the
      extrinsic compression. Endoscopy is a good tool for diagnosis of the
      subepithelial tumors, but not to determine the cause of an extrinsic compression.
      The endosonography identifies the layer from which subepithelial tumor comes,
      obtain histological samples, and increasing the diagnostic accuracy.

PMID- 22147128
TI  - Endoscopic mucosal resection in colorectal lesion: a safe and effective procedure
      even in lesions larger than 2 cm and in carcinomas.
AB  - CONTEXT: Endoscopic mucosal resection is a minimally invasive technique used in
      the treatment of colorectal neoplasms, including early carcinomas of different
      size and morphology. OBJECTIVES: To evaluate procedure safety, efficacy,
      outcomes, and recurrence rate in endoscopic mucosal resection of colorectal
      lesions. METHODS: A total of 172 lesions in 156 patients were analyzed between
      May 2003 and May 2009. All lesions showed pit pattern suggestive of neoplasia
      (Kudo types III-V) at high-magnification chromocolonoscopy with indigo carmine.
      The lesions were evaluated for macroscopic classification, size, location, and
      histopathology. Lesions 20 mm or smaller were resected en bloc and lesions larger
      than 20 mm were removed using the piecemeal technique. Complications and
      recurrence were analyzed. Patients were followed up for 18 months. RESULTS: There
      were 83 (48.2%) superficial lesions, 57 (33.1%) depressed lesions, 44 (25.6%)
      laterally spreading tumors, and 45 (26.2%) protruding lesions. Mean lesion size
      was 11.5 mm +/- 9.6 mm (2 mm-60 mm). Patients' mean age was 61.6 +/- 12.5 years
      (34-93 years). Regarding lesion site, 24 (14.0%) lesions were located in the
      rectum, 68 (39.5%) in the left colon, and 80 (46.5%) in the right colon
      (transverse, ascending, and cecum). There were 167 (97.1%) neoplasms: 142 (82.5%)
      adenomatous lesions, 24 (14.0%) intramucosal carcinomas, and 1 (0.6%) invasive
      carcinoma. En bloc resection was performed in 158 (91.9%) cases and piecemeal
      resection in 14 (8.1%). Bleeding occurred in 5 (2.9%) cases. Recurrence was
      observed in 4.1% (5/122) of cases and was associated with lesions larger than 20
      mm (P<0.01), piecemeal resection (P<0.01), advanced neoplasm (P = 0.01), and
      carcinoma compared to adenoma (P = 0.04). CONCLUSIONS: Endoscopic mucosal
      resection of colorectal lesions is a safe and effective procedure, with low
      complication and local recurrence rates. Recurrence is associated with lesions
      larger than 20 mm and carcinomas.

PMID- 22147129
TI  - Prospective study of bacteremia rate after elective band ligation and
      sclerotherapy with cyanoacrylate for esophageal varices in patients with advanced
      liver disease.
AB  - CONTEXT: Band ligation (BL) is the most appropriate endoscopic treatment for
      acute bleeding or prophylaxis of esophageal variceal bleeding. Sclerotherapy with
      N-butyl-2-cyanoacrylate (CY) can be an alternative for patients with advanced
      liver disease. Bacteremia is an infrequent complication after BL while the
      bacteremia rate following treatment with CY for esophageal varices remains
      unknown. OBJECTIVES: To evaluate and compare the incidence of transient
      bacteremia between cirrhotic patients submitted to diagnostic endoscopy, CY and
      BL for treatment of esophageal varices. METHODS: A prospective study comprising
      the period from 2004 to 2007 was conducted at Hospital of Universidade Federal de
      Sao Paulo, UNIFESP, SP, Brazil. Cirrhotic patients with advanced liver disease
      (Child-Pugh B or C) were enrolled. The patients were divided into two groups
      according treatment: BL Group (patients undergoing band ligation, n = 20) and CY
      Group (patients receiving cyanoacrylate injection for esophageal variceal, n =
      18). Cirrhotic patients with no esophageal varices or without indication for
      endoscopic treatment were recruited as control (diagnostic group n = 20).
      Bacteremia was evaluated by blood culture at baseline and 30 minutes after the
      procedure. RESULTS: After 137 scheduled endoscopic procedures, none of the 58
      patients had fever or any sign suggestive of infection. All baseline cultures
      were negative. No positive cultures were observed after CY or in the control
      group - diagnostic endoscopy. Three (4.6 %) positive cultures were found out of
      the 65 sessions of band ligation (P = 0.187). Two of these samples were positive
      for coagulase-negative staphylococcus, which could be regarded as a contaminant.
      The isolated microorganism in the other case was Klebsiella oxytoca. The patient
      in this case presented no evidence of immunodeficiency except liver disease.
      CONCLUSIONS: There was no significant difference in bacteremia rate between these
      three groups. BL or CY injection for non-bleeding esophageal varices may be
      considered as low-risk procedures regarding bacteremia even when performed on
      patients with advanced liver disease.

PMID- 22147130
TI  - Surgical treatment of gastroesophageal reflux disease: total or partial
      fundoplication? systematic review and meta-analysis.
AB  - CONTEXT: Although the high incidence of gastroesophageal reflux disease (GERD) in
      the population, there is much controversy in this topic, especially in the
      surgical treatment. The decision to use of a total or partial fundoplication in
      the treatment of GERD is still a challenge to many surgeons because the few
      evidence found in the literature. OBJECTIVE: To bring more clear evidence in the
      comparison between total and partial fundoplication. DATA SOURCES: A systematic
      review of the literature and metaanalysis with randomized controlled trials
      accessed from MEDLINE, LILACS, Cochrane Controlled Trials Database was done. The
      outcomes remarked were: dysphagia, inability to belch, bloating, recurrence of
      acid reflux, heartburn and esophagitis. For data analysis the odds ratio was used
      with corresponding 95% confidence interval. Statistical heterogeneity in the
      results of the metaanalysis was assessed by calculating a test of heterogeneity.
      The software Review Manager 5 (Cochrane Collaboration) was utilized for the data
      gathered and the statistical analysis. Sensitive analysis was applied using only
      trials that included follow-up over 2 years. RESULTS: Ten trials were included
      with 1003 patients: 502 to total fundoplication group and 501 to partial
      fundoplication group. The outcomes dysphagia and inability to belch had
      statistical significant difference (P = 0.00001) in favor of partial
      fundoplication. There was not statistical difference in outcomes related with
      treatment failure. There were no heterogeneity in the outcomes dysphagia and
      recurrence of the acid reflux. CONCLUSION: The partial fundoplication has lower
      incidence of obstructive side effects.

PMID- 22147131
TI  - Helicobacter pylori antibiotic resistance in Brazil: clarithromycin is still a
      good option.
AB  - CONTEXT: The antibiotic susceptibility is the cornerstone for the eradication
      therapies of Helicobacter pylori. OBJECTIVES: To evaluate the prevalence of
      primary resistance of H. pylori was evaluated in an urban Brazilian population.
      METHODS: H. pylori isolates were obtained from patients submitted to an upper
      gastrointestinal endoscopy for the evaluation of dyspeptic symptoms. Biopsies
      from antrum, corpus and fundus were taken to determine the antibiotic
      susceptibility of H. pylori isolates. The minimal inhibitory concentration of
      furazolidone and bismuth were routinely determined by agar dilution method and
      the minimal inhibitory for amoxicillin, clarithromycin, tetracycline,
      levofloxacin, and metronidazole were routinely determined with the E-test.
      RESULTS: Fifty-four patients were included. In vitro antimicrobial susceptibility
      of H. pylori strains were obtained from 39 patients. Resistance to metronidazole
      was detected in 20 patients (51%), to clarithromycin in 3 patients (8%), to
      levofloxacin in 9 patients (23%) and to bismuth in 2 patients (5%). There was no
      observed resistance to amoxicillin, tetracycline or furazolidone. CONCLUSION: Due
      to the low amoxicillin and clarithromycin resistance observed in this study,
      therapies using these antimicrobials remain appropriated first-line H. pylori
      therapy.

PMID- 22147132
TI  - Influence of age, mode of delivery and parity on the prevalence of posterior
      pelvic floor dysfunctions.
AB  - CONTEXT: The correlation between vaginal delivery, age and pelvic floor
      dysfunctions involving obstructed defecation is still a matter of controversy.
      OBJECTIVES: To determine the influence of age, mode of delivery and parity on the
      prevalence of posterior pelvic floor dysfunctions in women with obstructed
      defecation syndrome. METHODS: Four hundred sixty-nine females with obstructed
      defecation syndrome were retrospectively evaluated using dynamic 3D
      ultrasonography to quantify posterior pelvic floor dysfunctions (rectocele grade
      II or III, rectal intussusception, paradoxical contraction/non-relaxation of the
      puborectalis and entero/ sigmoidocele grade III). In addition, sphincter damage
      was evaluated. Patients were grouped according to age (<=50y x >50y) and
      stratified by mode of delivery and parity: group I (<=50y): 218 patients, 75
      nulliparous, 64 vaginal delivery and 79 only cesarean section and group II
      (>50y): 251 patients, 60 nulliparous, 148 vaginal delivery and 43 only caesarean
      section. Additionally, patients were stratified by number of vaginal deliveries:
      0 - nulliparous (n = 135), 1 - vaginal (n = 46), >1 - vaginal (n = 166). RESULTS:
      Rectocele grade II or III, intussusception, rectocele + intussusception and
      sphincter damage were more prevalent in Group II (P = 0.0432; P = 0.0028; P =
      0.0178; P = 0.0001). The stratified groups (nulliparous, vaginal delivery and
      cesarean) did not differ significantly with regard to rectocele, intussusception
      or anismus in each age group. Entero/sigmoidocele was more prevalent in the
      vaginal group <50y and in the nulliparous and vaginal groups >50y. No correlation
      was found between rectocele and the number of vaginal deliveries. CONCLUSION:
      Higher age (>50 years) was shown to influence the prevalence of significant
      rectocele, intussusception and sphincter damage in women. However, delivery mode
      and parity were not correlated with the prevalence of rectocele, intussusception
      and anismus in women with obstructed defecation.

PMID- 22147133
TI  - Locally advanced colorectal cancer: results of surgical treatment and prognostic
      factors.
AB  - OBJECTIVES: To evaluate the incidence surgical results and prognostic factors of
      locally advanced colorectal cancer. METHODS: Cohort study including 679
      colorectal cancer patients treated from 1997 to 2007. Clinical, surgical and
      histological data were analyzed. RESULTS: Ninety patients (females 61%; median
      age 59 years) were treated for locally advanced carcinomas (13.2%), either in the
      colon (66%) or rectum (34%). Extended resections most commonly involved the small
      bowel (19.8%), bladder (16.4%), uterus (12.9%) and ovaries (11.2%). Postoperative
      morbidity and mortality occurred in 23 (25.6%) and 3 (3.3%) patients,
      respectively. Survival and recurrence analysis among 76 R0 (84.4%) procedures
      revealed a 60% 5-year survival and 34% local recurrence rates. Survival curves
      demonstrated reduced rates for rectal location (45% vs 65%), tumor depth (50% for
      T4 vs 75% for T3), vascular/ lymphatic/perineural invasion (35% vs 80%) and lymph
      node metastasis (35% vs 80%). CONCLUSIONS: Locally advanced carcinomas were found
      in 13.2% of patients. Survival rates were negatively affected by rectal location
      and adverse histological features. Number of involved organs and neoplastic
      adhesions did not influenced chances of survival. A radical R0 extended resection
      was achieved in a high proportion of cases, resulting in a 60% cancer-free
      survival under acceptable operative risks.

PMID- 22147134
TI  - Evaluation of antiulcerogenic activity of aqueous extract of Brassica oleracea
      var. capitata (cabbage) on Wistar rat gastric ulceration.
AB  - CONTEXT: The cabbage (Brassica oleraceae var. capitata) is an herbaceous and
      leafy plant which belongs to the Brassicaceae family, native to coastal southern
      and Western Europe. Used in cooking for its nutritional value also has known anti
      inflammatory activity. OBJECTIVE We studied the antiulcerogenic activity of
      aqueous extract of Brassica oleracea var. capitata (AEB) in order to validate
      ethnobotanical claims regarding the plant use in the gastric disorders. METHOD:
      Acute gastric ulcers were induced in rats by the oral administration of
      acetylsalicylic acid. The gastroprotective potential of the AEB (0.250, 0.500 and
      1.000 mg.kg-1/body weight) was compared with omeprazole (20 mg.kg-1/body weight).
      RESULTS: The stomach analysis indicated that treatment with AEB inhibited the
      gastric damage. The gastroprotective activity as evidenced by its significant
      inhibition in the formation of ulcers induced by chemical agent with a maximum of
      99.44% curation (250 mg.kg-1 body weight) in acetylsalicylic acid-induced ulcers.
      CONCLUSIONS: The AEB demonstrated good antiulcerogenic activities which justify
      the inclusion of this plant in the management of gastric disorders. Further
      experiments are underway to determine which antiulcer mechanisms involved in
      gastroprotection.

PMID- 22147135
TI  - A morphometric study of the intestinal mucosa of rats submitted to
      omentoenteropexy.
AB  - CONTEXT: The omentoenteropexy technique was developed as an alternative method
      for intestinal neovascularization, due to the angiogenic properties of factors
      from the omentum. OBJECTIVES: This study investigated changes in intestinal villi
      heights and crypts depths due to surgical techniques: seromiotomy with and
      without omentoenteropexy. METHOD: Thirty rats were operated on, after being
      divided into three groups, namely GI, GII and GIII with 10 rats each. In the GI
      rats were submitted to omentoenteropexy; rats in GII were submitted only to a
      seromiotomy, and in the GIII only laparotomy. Sixty days after the first surgery,
      the animals were sacrificed and a segment of intestine was removed for histology
      using Masson's trichrome technique and morphometric study of intestinal mucosa.
      RESULTS: The histological findings showed that seromiotomy with or without
      omentoenteropexy increased the length of intestinal villi when compared with GIII
      (only laparotomy) (analysis of variance: P = 0.0068; GI 38.88 +/- 4.17; GII
      39.41+/- 6.33; GIII 31.85 +/- 5.56; GI = GII P>0.05; GII>GIII P<0.05; GI>GIII
      P<0.001). CONCLUSION: No differences were demonstrated in relation to crypt
      depths between the groups (P = 0.60). Ongoing studies are being set forth by our
      group to add more data on the role of omentopexy as a tool to promote
      neovascularization and intestinal mucosal growth.

PMID- 22147136
TI  - Isolation of centromeric-tandem repetitive DNA sequences by chromatin affinity
      purification using a HaloTag7-fused centromere-specific histone H3 in tobacco.
AB  - The centromere is a multi-functional complex comprising centromeric DNA and a
      number of proteins. To isolate unidentified centromeric DNA sequences, centromere
      specific histone H3 variants (CENH3) and chromatin immunoprecipitation (ChIP)
      have been utilized in some plant species. However, anti-CENH3 antibody for ChIP
      must be raised in each species because of its species specificity. Production of
      the antibodies is time-consuming and costly, and it is not easy to produce ChIP
      grade antibodies. In this study, we applied a HaloTag7-based chromatin affinity
      purification system to isolate centromeric DNA sequences in tobacco. This system
      required no specific antibody, and made it possible to apply a highly stringent
      wash to remove contaminated DNA. As a result, we succeeded in isolating five
      tandem repetitive DNA sequences in addition to the centromeric retrotransposons
      that were previously identified by ChIP. Three of the tandem repeats were
      centromere-specific sequences located on different chromosomes. These results
      confirm the validity of the HaloTag7-based chromatin affinity purification system
      as an alternative method to ChIP for isolating unknown centromeric DNA sequences.
      The discovery of more than two chromosome-specific centromeric DNA sequences
      indicates the mosaic structure of tobacco centromeres.

PMID- 22147137
TI  - Different fertility and meiotic regularity in allohexaploids derived from
      trigenomic hybrids between three cultivated Brassica allotetraploids and B.
      maurorum.
AB  - The wild species Brassica maurorum Durieu (MM, 2n = 16) is useful for the
      improvement of Brassica crops. Herein, interspecific reciprocal crosses between
      B. maurorum and three cultivated Brassica allotetraploids were carried out with
      the aid of embryo rescue. Trigenomic hybrids with Brassica napus (AACC, 2n = 38)
      and Brassica carinata (BBCC, 2n = 34) were produced from reciprocal crosses, but
      the hybrids with Brassica juncea (AABB, 2n = 36) were obtained only when B.
      maurorum was used as female. All the hybrids were morphologically intermediate
      between their parents, and were male and female sterile. By in vitro chromosome
      doubling of the trigenomic hybrids, the allohexaploids (AACC.MM/MM.AACC, 2n = 54;
      BBCC.MM, 2n = 50; MM.AABB, 2n = 52) were established and characterized for their
      phenotype and cytology. The fertilities of three allohexaploids were different,
      for AACC.MM and MM.AACC failed to produce seeds by selfing, but BBCC.MM showed
      low seed-set and MM.AABB had good seed-set. They also expressed variable extents
      of male meiotic regularity as to chromosome pairing and segregation, with MM.AABB
      > BBCC.MM > AACC.MM/MM.AACC, the same order as their fertility. So their meiotic
      behavior contributed to the fertility. Finally, the potential of these
      allohexaploids as a bridge for genetic improvement of Brassica crops was
      discussed.

PMID- 22147138
TI  - It is time to reconsider the cardiovascular protection afforded by RAAS blockade 
      - overview of RAAS systems.
AB  - More than a century has passed since the renin-angiotensin-aldosterone system
      (RAAS) was discovered in 1897. Both circulatory and tissue RAAS have been found
      to be essential for regulation of the functions of the whole body, organs,
      tissues and cells. There is no doubt that the RAAS plays fundamental
      physiological roles in maintaining homeostasis, but it can also contribute to
      organ pathophysiology and tissue damages in some situations. Today, the
      usefulness of RAAS blockade is well-established in the management of a variety of
      cardiovascular disorders worldwide. However, the latest findings in this field
      are still providing us with new and unexpected insights into the pathophysiology
      of cardiovascular diseases. Such developments include dual blockade therapy with
      angiotensin I converting enzyme inhibitors (ACEIs) and angiotensin II receptor
      blockers (ARBs), and a new class of RAAS blockers, renin inhibitors. These give
      us the opportunity to revisit the basic principles of the RAAS and reconsider the
      strategies of RAAS blockade for cardiovascular protection.

PMID- 22147139
TI  - Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role
      for ERK 1/2 MAPK signaling.
AB  - Cyclosporine A (CsA) is a potent immunosuppressant used to prevent organ
      transplant rejection and in the treatment of autoimmune diseases. However,
      chronic CsA nephropathy is the major limiting factor to its widespread use. The
      exact mechanisms of CsA-induced renal damage remain to be fully elucidated. The
      objective of the current research was to examine whether CsA treatment induced
      any glomerular mesangial cell alterations. In this research goal, human mesangial
      cells (HMCs) were treated with CsA for various time points. CsA caused an
      increase in the production of reactive oxygen species (ROS). Microarray analysis
      of mesangial cells treated with CsA also indicated 282 dysregulated genes.
      Bioinformatic analysis of these 282 genes indicated enriched apoptotic oxidative
      stress, mitogen-activated protein kinase (MAPK), and transforming growth factor
      beta signaling in response to CsA treatment. The focus of this study was directed
      on oxidative stress and MAPK signaling as potential novel mechanisms of CsA
      nephrotoxicity. One key contributor to oxidative stress, thioredoxin interacting
      protein, was significantly upregulated following CsA treatment. Inhibition of the
      MAPK pathway resulted in attenuation of the CsA-induced mesangial cell
      alterations. These findings suggest a major role for ROS, oxidative stress, and
      MAPK signaling in promoting CsA-induced glomerular dysfunction and subsequent
      nephrotoxicity.

PMID- 22147144
TI  - Ketamine in adult emergency medicine: controversies and recent advances.
AB  - OBJECTIVE: To review the evidence for the use of ketamine in adult emergency
      medicine for procedural sedation and analgesia (PSA) and rapid sequence
      intubation (RSI), as well as to focus on the issues of recovery agitation,
      combination with propofol for PSA, and the use of ketamine as an induction agent
      in patients with acute head injury in need of definitive airway management. DATA
      SOURCES: PubMed (1949-July 2011), EMBASE (1980-July 2011), Google Scholar (to
      July 2011), International Pharmaceutical Abstracts (1964-July 2011), and Cochrane
      databases were searched independently. A manual search of references was also
      performed. STUDY SELECTION: English-language, full reports of experimental and
      observational studies evaluating ketamine in adults undergoing PSA and RSI in the
      emergency department (ED) were included if they reported efficacy or safety
      outcomes. DATA EXTRACTION: Two reviewers independently assessed each article for
      inclusion, data extraction, and study limitations. DATA SYNTHESIS: Six studies
      that used ketamine for PSA were included. The majority reported adequate sedation
      with high patient satisfaction and lack of pain and procedural recall. There is
      no evidence to support the superiority of a combination of ketamine and propofol
      compared to propofol alone for PSA in adults. Recovery agitation is common but
      can be minimized with premedication with midazolam (number needed to treat 6).
      Two studies were identified that evaluated the role of ketamine for induction
      during RSI in the ED. Although ketamine is not a first-line agent for RSI, it is
      an alternative and may be used as an induction agent in patients requiring
      endotracheal intubation. CONCLUSIONS: Ketamine is an effective agent in adults
      undergoing PSA and RSI in the ED. The best available evidence provides sufficient
      confidence to consider use of this agent in the ED.

PMID- 22147145
TI  - Disparities in blood pressure control within a community-based provider network:
      an exploratory analysis.
AB  - BACKGROUND: Despite treatment for hypertension, blood pressure (BP) remains
      uncontrolled in many individuals. Identification of patterns in BP control may
      inform strategies to improve treatment and optimize health outcomes. OBJECTIVE:
      To examine patterns in BP control among individuals receiving antihypertensive
      treatment in a diverse, community-based provider network. METHODS: In this
      retrospective exploratory analysis, a total of 51,772 hypertensive subjects were
      identified in the electronic medical record between January 1, 2007, and June 30,
      2010, who were aged 18 years or older, with 2 or more claims for antihypertensive
      medication, documented race/ethnicity, and 1 or more documented BP readings.
      RESULTS: On the basis of Joint National Committee VII guidelines, 76.4% of
      nondiabetic patients had their BP controlled with treatment (<140/90 mm Hg) and
      52.3% of those with diabetes had their BP controlled with treatment (<130/80 mm
      Hg). The overall rate of BP control was 71.4%. Factors associated with controlled
      BP included younger age, lower disease burden, better medication adherence, fewer
      concurrent prescriptions, lower prescription copayments, and living in a region
      with a higher median household income. Furthermore, when adjusting for age, sex,
      and disease burden, black (OR 0.68; 95% CI 0.62 to 0.75; p < 0.001), Hispanic (OR
      0.80; 95% CI 0.74 to 0.86; p < 0.001), and other race/ethnic group (OR 0.81; 95%
      CI 0.70 to 0.94; p = 0.005) individuals were less likely than white individuals
      to have their treated BP controlled. Among nondiabetic hypertensive subjects with
      controlled BP, the most frequently prescribed therapy was a beta-blocker or an
      angiotensin-converting enzyme (ACE) inhibitor across race/ethnicities; however,
      those who were black were most frequently prescribed a diuretic or calcium
      channel blocker. Among diabetic patients with controlled BP, the most frequently
      prescribed therapy was an ACE inhibitor, regardless of race/ethnicity.
      CONCLUSIONS: Potential disparities, particularly among diabetic individuals and
      those of minority race/ethnicity, were found with regard to BP control and the
      agents used to treat hypertension. Future studies should address these
      disparities by designing interventions to improve the treatment of hypertension
      in high-risk populations.

PMID- 22147192
TI  - Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated
      with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra.
AB  - Neonatal Sprague-Dawley rats were randomly divided into normal control, mild
      hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time)
      on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like
      behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra
      (SN). The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2) for 90
      and 150 min, respectively. The elevated plus-maze (EPM) test was performed to
      assess anxiety-like behavior by measuring time spent in the open arms (OAT) and
      OAT%, and immunohistochemistry was used to determine the expression of TH in the
      SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in
      both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and
      severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold,
      respectively; P < 0.05). The percent of TH-positive cells occupying the SN area
      was significantly and similarly decreased in both the mild (17.7, 40.2, and
      47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The
      decrease in the number of TH-positive cells in the SN and the level of protein
      expression were closely associated (Pearson correlation analysis: r = 0.991, P =
      0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with
      the impaired anxiety-like behaviors. We conclude that neonatal HI results in
      decreased anxiety-like behavior during the juvenile period of Sprague-Dawley
      rats, which is associated with the decreased activity of TH in the SN. The
      impairment of anxiety and the expression of TH are not likely to be dependent on
      the severity of HI.

PMID- 22147193
TI  - MTP -493G/T gene polymorphism is associated with steatosis in hepatitis C
      infected patients.
AB  - The reduction of hepatic microsomal transfer protein (MTP) activity results in
      fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C
      (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with
      lower transcriptional activity than the T allele. We investigated this
      association with metabolic and histological variables in patients with CHC. A
      total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct
      sequencing using PCR. All patients were negative for markers of Wilson's disease,
      hemochromatosis and autoimmune diseases and had current and past daily alcohol
      intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg
      equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis
      grade 3+4 presented at least one G allele versus 34.3% of the patients with
      fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with
      steatosis as the dependent variable identified genotypes GG+GT as independent
      protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The
      results suggest that the presence of the G allele of MTP -493G/T associated with
      lower hepatic MTP expression protects against steatosis in our CHC patients.

PMID- 22147194
TI  - [Importance of education level for effectiveness of multimodal pain therapy].
AB  - BACKGROUND: The recommended treatment for chronic pain is multidisciplinary with
      a cognitive approach. The aim of this study was to investigate whether the
      education level of patients was predictive of main outcome dimensions (pain
      intensity, disability, depression, physical functioning and return to work).
      PATIENTS AND METHODS: This was a secondary analysis of 413 patients who
      participated in an in-patient multidisciplinary pain treatment program. All
      patients were studied at baseline and after 6 months. The aim was to find
      predictors for the changes in scores of outcome measures (from admission to
      follow-up). Possible predictors were educational level and other available
      variables that are considered prognostic of treatment outcome, including age,
      gender, body mass index, endurance of pain, pain intensity, depressive symptoms
      and work status. Classification trees were used to predict outcome variables.
      RESULTS: The outcome was markedly improved in the sampling collective at follow
      up compared with baseline. Education was the best predictor of treatment outcome
      and affected 4 out of the 5 outcome dimensions analyzed. CONCLUSION: If education
      level proves to be an intervening variable in further research, education
      adjusted treatment programs should be developed and evaluated.

PMID- 22147195
TI  - The hypoxic preconditioning agent deferoxamine induces poly(ADP-ribose)
      polymerase-1-dependent inhibition of the mitochondrial respiratory chain.
AB  - We previously reported that treatment with a single dose of deferoxamine (DFO),
      which acts as a hypoxic-mimetic agent, only induces reactive oxygen species (ROS)
      production in the presence of poly(ADP-ribose) polymerase (PARP-1). Given that
      mitochondria are one of the main sources of ROS, the present study was designed
      to assess the effect of DFO treatment on the activity of mitochondrial
      respiratory chain complexes, and more importantly, to determine whether this
      effect is modulated by PARP-1. We found that DFO treatment induced a progressive
      decline in complex II and IV activity, but that this activity was preserved in
      PARP-1 knock-out cells, demonstrating that this decrease is mediated by PARP-1.
      We also confirmed that complex II inhibition after DFO treatment occurs in
      parallel with poly-ADP ribosylation. Consequently, we recommend that PARP-1
      activation be taken into account when using DFO as a hypoxia-mimetic agent,
      because it mediates alteration of the mitochondrial respiratory chain.

PMID- 22147196
TI  - Beta-hexosaminidase over-expression affects lysosomal glycohydrolases expression
      and glycosphingolipid metabolism in mammalian cells.
AB  - Lysosomes are not only degrading organelles but also involved in other critical
      cellular processes. In addition, active lysosomal glycohydrolases have been
      detected in an extra-lysosomal compartment: the presence of glycohydrolases on
      the plasma membrane (PM) has been widely demonstrated, and a possible role on the
      modification of the cell surface glycosphingolipids (GSL) participating in the
      modulation of cell functions such as cell-to-cell interactions and signal
      transduction pathways has been proposed. On this basis, the coordinated
      expression of lysosomal glycohydrolases and their translocation to the PM appear
      to be crucial for many cellular events. In this paper, we report evidence for the
      existence of a coordinated mechanism regulating the expression/activity of both
      lysosomal and PM-associated glycohydrolases. We show that the over-expression of
      the acidic glycohydrolase beta-hexosaminidase alpha-subunit in mouse NIH/3T3
      fibroblasts induces the increased expression of the Hex beta-subunit necessary to
      form the active isoenzyme dimers as well as of other glycohydrolases
      participating in the GSL catabolism, such as beta-galactosidase and beta
      glucocerebrosidase. More interestingly, this regulatory effect was also extended
      to the PM-associated hydrolases. In addition, transfected cells displayed a
      rearrangement of the GSL expression pattern that cannot be simply explained by
      the increased activity of a single enzyme. These observations clearly indicate
      that the expression level of metabolically related glycohydrolases is regulated
      in a coordinated manner and this regulation mechanism also involves the PM
      associated isoforms.

PMID- 22147197
TI  - Induction of Fas-mediated extrinsic apoptosis, p21WAF1-related G2/M cell cycle
      arrest and ROS generation by costunolide in estrogen receptor-negative breast
      cancer cells, MDA-MB-231.
AB  - Costunolide (C(15)H(20)O(2)) is a sesquiterpene lactone that was isolated from
      many herbal medicines and it has diverse effects according to previous reports.
      However, the anti-cancer effects and the mechanism of actions are still unknown
      in breast cancer. In this study, we first observed that costunolide inhibits cell
      growth in a dose-and time-dependent manner. To examine the mechanism by which
      costunolide inhibits cell growth, we checked the effect of costunolide on
      apoptosis and the cell cycle. Costunolide induced apoptosis through the extrinsic
      pathway, including the activation of Fas, caspase-8, caspase-3, and degradation
      of PARP. However, did not have the same effect on the intrinsic pathway as
      revealed by analysis of mitochondrial membrane potential (Deltapsim) with JC-1
      dye and expression of Bcl2 and Bax proteins level. Furthermore, costunolide
      induced cell cycle arrest in the G2/M phase via decrease in Cdc2, cyclin B1 and
      increase in p21WAF1 expression, independent of p53 pathway in p53-mutant MDA-MB
      231 cells and increases Cdc2-p21WAF1 binding. In addition, costunolide had a
      slight induced effect on ROS generation. Among the mechanisms of p21WAF1
      induction examined, costunolide-induced increase in p21WAF1 expression was
      related with protein stability and ROS generation. Through this study we confirm
      that costunolide induces G2/M cell cycle arrest and apoptotic cell death via
      extrinsic pathway in MDA-MB-231 cells suggesting that it could be a promising
      anticancer drug especially for ER-negative breast cancer.

PMID- 22147198
TI  - Alcohol-associated folate disturbances result in altered methylation of folate
      regulating genes.
AB  - Folate plays a critical role in maintaining normal metabolic, energy,
      differentiation and growth status of all mammalian cells. The steady-state
      accumulation of folate seems to depend on the activity of two enzymes:
      folylpolyglutamate synthetase (FPGS), which adds glutamate residues, and gamma
      glutamyl hydrolase (GGH), which removes them, enabling it to be transported
      across the biological membranes. Overexpression of GGH and downregulation of FPGS
      would be expected to decrease intracellular folate in its polyglutamylated form,
      thereby increasing efflux of folate and its related molecules, which might lead
      to resistance to drugs or folate deficiency. The study was sought to delineate
      the activity of GGH and expression FPGS in tissues involved in folate homeostasis
      during alcoholism and the epigenetic regulation of these enzymes and transporters
      regulating intracellular folate levels. We determined the activity of GGH and
      expression of FPGS in tissues after 3 months of ethanol feeding to rats at 1 g/kg
      body weight/day. The results showed that there was not any significant change in
      the activity of folate hydrolyzing enzyme GGH in ethanol-fed rats while there was
      significant down regulation in the expression of FPGS. Ethanol feeding decreased
      the total as well as polyglutamated folate levels. There was tissue-specific
      hyper/hypo methylation of folate transporter genes viz. PCFT and RFC by chronic
      ethanol feeding. Moreover, hypermethylation of FPGS gene was observed in
      intestine and kidney without any change in methylation levels of GGH in the
      ethanol-fed rats. In conclusion, the initial deconjugation of polyglutamylated
      folate by GGH was not impaired in ethanol-fed rats while the conversion of
      monoglutamylated folate to polyglutamylated form might be impaired. There was
      tissue-specific altered methylation of folate transporter genes by chronic
      ethanol feeding.

PMID- 22147199
TI  - Combination treatment with dihydrotanshinone I and irradiation enhances apoptotic
      effects in human cervical cancer by HPV E6 down-regulation and caspases
      activation.
AB  - The aim of this study was to investigate the effect of dihydrotanshinone I (DI)
      in inhibiting the growth of human cervical cancer cells both in vitro and in
      vivo, and molecular targets in HeLa cells when treated by DI or irradiation with
      or without being combined. In this study, MTT, clonogenic assay, flow cytometry,
      and Western blotting were performed to assess the effect of treatment on cells.
      After treatment with IR, DI, and DI + IR, the apoptosis was 5.8, 13.3 and 22.5%
      (P < 0.05 vs. control), respectively. Clonogenic assay revealed that the survival
      of irradiated HeLa cell was significantly reduced by DI treatment. Combination
      treatment with IR and DI could down-regulate HPV E6 gene expression. Effect of DI
      on up-regulation of p21 expression and down-regulation of cyclin B1, p34(cdc2)
      expression in irradiated HeLa cell was concomitant with cell cycle arrest in G(2)
      phase. The significant increase in caspase-3 activity was also observed in the
      combination treatment. When HeLa cells were grown as xenografts in nude mice,
      combination treatment with DI and IR induced a significant decrease in tumor
      growth, and without signs of general or organ toxicity. These data suggest DI
      should be tested as the radiosensitizer in vitro and in vivo, which has potential
      in the treatment of human cervical cancer.

PMID- 22147200
TI  - Magnetite induces oxidative stress and apoptosis in lung epithelial cells.
AB  - There is an ongoing concern regarding the biocompatibility of nanoparticles with
      sizes less than 100 nm as compared to larger particles of the same nominal
      substance. In this study, we investigated the toxic properties of magnetite
      stabilized with polyacrylate sodium. The magnetite was characterized by X-ray
      powder diffraction analysis, and the mean particle diameter was calculated using
      the Scherrer formula and was found to be 9.3 nm. In this study, we treated lung
      epithelial cells with different concentrations of magnetite and investigated
      their effects on oxidative stress and cell proliferation. Our data showed an
      inhibition of cell proliferation in magnetite-treated cells with a significant
      dose-dependent activation and induction of reactive oxygen species. Also, we
      observed a depletion of antioxidants, glutathione, and superoxide dismutase,
      respectively, as compared with control cells. In addition, apoptotic-related
      protease/enzyme such as caspase-3 and -8 activities, were increased in a dose
      dependent manner with corresponding increased levels of DNA fragmentation in
      magnetite-treated cells compared to than control cells. Together, the present
      study reveals that magnetite exposure induces oxidative stress and depletes
      antioxidant levels in the cells to stimulate apoptotic pathway for cell death.

PMID- 22147201
TI  - Mechanistic insights into the link between visfatin gene C-1535T polymorphism and
      coronary artery disease: an in vitro study.
AB  - Visfatin, a pro-inflammatory cytokine predominantly released from leucocytes, is
      correlated with coronary artery disease (CAD). We have previously reported that
      the -1535C>T polymorphism (rs1330082), which located on the promoter region of
      visfatin, was associated with decreased risk of CAD. Here, we investigated the
      underlying mechanism by which this polymorphism affects the genetic
      susceptibility to CAD. The difference of the promoter activities between -1535T
      variant and -1535C allele was tested by luciferase reporter gene assay. The
      difference of transcription factor binding activities between T and C allele was
      evaluated by electrophoretic mobility shift assay. In reporter gene assay, we
      showed that the T variant had a significantly reduced transcriptional activity
      compared with the C allele. The T-variant significantly attenuated the promoter
      binding affinity to nuclear transcription factors and this effect became much
      obvious after treatment with TNF-alpha. Moreover, competition experiment revealed
      that the retarded complex formed by T-1535- or C-1535-probe binding to nuclear
      extracts was nearly completely inhibited by unlabeled activator protein-1 (AP-1)
      specific probe, indicating that AP-1 might be the target nuclear effector. Taken
      together, our data provided potential mechanistic link between the visfatin 
      1535C>T polymorphism and reduced CAD risk.

PMID- 22147202
TI  - Effects of the long-term administration of nebivolol on the clinical symptoms,
      exercise capacity, and left ventricular function of patients with diastolic
      dysfunction: results of the ELANDD study.
AB  - AIMS: We hypothesized that nebivolol, a beta-blocker with nitric oxide-releasing
      properties, could favourably affect exercise capacity in patients with heart
      failure and preserved left ventricular ejection fraction (HFPEF). METHODS AND
      RESULTS: A total of 116 subjects with HFPEF, in New York Heart Association (NYHA)
      functional class II-III, with left ventricular ejection fraction (LVEF) >45%, and
      with echo-Doppler signs of LV diastolic dysfunction, were randomized to 6 months
      treatment with nebivolol or placebo, following a double-blind, parallel group
      design. The primary endpoint of the study was the change in 6 min walk test
      distance (6MWTD) after 6 months. Nebivolol did not improve 6MWTD (from 420 +/-
      143 to 428 +/- 141 m with nebivolol vs. from 412 +/- 123 to 446 +/- 119 m with
      placebo, P = 0.004 for interaction) compared with placebo, and the peak oxygen
      uptake also remained unchanged (peakVO(2); from 17.02 +/- 4.79 to 16.32 +/- 3.76
      mL/kg/min with nebivolol vs. from 17.79 +/- 5.96 to 18.59 +/- 5.64 mL/kg/min with
      placebo, P = 0.63 for interaction). Resting and peak blood pressure and heart
      rate decreased with nebivolol. A significant correlation was found between the
      change in peak exercise heart rate and that in peakVO(2) (r = 0.391; P = 0.003)
      for the nebivolol group. Quality of life, assessed using the Minnesota Living
      with Heart Failure Questionnaire, and NYHA classification improved to a similar
      extent in both groups, whereas N-terminal pro brain natriuretic peptide (NT-pro
      BNP) plasma levels remained unchanged. CONCLUSIONS: Compared with placebo, 6
      months treatment with nebivolol did not improve exercise capacity in patients
      with HFPEF. Its negative chronotropic effect may have contributed to this result.

PMID- 22147203
TI  - Cardiac regeneration in left ventricular dysfunction: are we asking the right
      questions?

PMID- 22147204
TI  - Probing the chemical and electronic properties of the core-shell architecture of
      transition metal trisulfide nanoribbons.
AB  - Ultraviolet and X-ray photoelectron spectroscopies are used to probe the chemical
      and electronic structure of an amorphous, 2-20 nm-thick shell that encases the
      crystalline core in core-shell nanoribbons of TaS(3). The shell is chemically
      heterogeneous, containing elemental sulfur and a with a notable (S(2))(2-)
      deficiency over the crystalline TaS(3) core. We find nanoribbon stability to be
      substrate-dependent; whilst the ribbons are stable on the native oxide of a
      silicon surface, mass transport of sulfur species between the amorphous shell and
      a gold substrate leads to a significant change in the electronic properties of
      the nanomaterials. Our observations may have general implications for the
      incorporation of nanostructured transition metal chalcogenides into electronic
      devices.

PMID- 22147205
TI  - Canine models of copper toxicosis for understanding mammalian copper metabolism.
AB  - Hereditary forms of copper toxicosis exist in man and dogs. In man, Wilson's
      disease is the best studied disorder of copper overload, resulting from mutations
      in the gene coding for the copper transporter ATP7B. Forms of copper toxicosis
      for which no causal gene is known yet are recognized as well, often in young
      children. Although advances have been made in unraveling the genetic background
      of disorders of copper metabolism in man, many questions regarding disease
      mechanisms and copper homeostasis remain unanswered. Genetic studies in the
      Bedlington terrier, a dog breed affected with copper toxicosis, identified
      COMMD1, a gene that was previously unknown to be involved in copper metabolism.
      Besides the Bedlington terrier, a number of other dog breeds suffer from
      hereditary copper toxicosis and show similar phenotypes to humans with copper
      storage disorders. Unlike the heterogeneity of most human populations, the
      genetic structure within a purebred dog population is homogeneous, which is
      advantageous for unraveling the molecular genetics of complex diseases. This
      article reviews the work that has been done on the Bedlington terrier, summarizes
      what was learned from studies into COMMD1 function, describes hereditary copper
      toxicosis phenotypes in other dog breeds, and discusses the opportunities for
      genome-wide association studies on copper toxicosis in the dog to contribute to
      the understanding of mammalian copper metabolism and copper metabolism disorders
      in man.

PMID- 22147206
TI  - Arbuscular mycorrhizal fungi affect both penetration and further life stage
      development of root-knot nematodes in tomato.
AB  - The root-knot nematode Meloidogyne incognita poses a worldwide threat to
      agriculture, with an increasing demand for alternative control options since most
      common nematicides are being withdrawn due to environmental concerns. The
      biocontrol potential of arbuscular mycorrhizal fungi (AMF) against plant
      parasitic nematodes has been demonstrated, but the modes of action remain to be
      unraveled. In this study, M. incognita penetration of second-stage juveniles at
      4, 8 and 12 days after inoculation was compared in tomato roots (Solanum
      lycopersicum cv. Marmande) pre-colonized or not by the AMF Glomus mosseae.
      Further life stage development of the juveniles was also observed in both control
      and mycorrhizal roots at 12 days, 3 weeks and 4 weeks after inoculation by means
      of acid fuchsin staining. Penetration was significantly lower in mycorrhizal
      roots, with a reduction up to 32%. Significantly lower numbers of third- and
      fourth-stage juveniles and females accumulated in mycorrhizal roots, at a slower
      rate than in control roots. The results show for the first time that G. mosseae
      continuously suppresses root-knot nematodes throughout their entire early
      infection phase of root penetration and subsequent life stage development.

PMID- 22147207
TI  - Risk of lymphoma in patients receiving antitumor necrosis factor therapy: a meta
      analysis of published randomized controlled studies.
AB  - The 2008 edition of the WHO Classification of Tumours of Haematopoietic and
      Lymphoid tissues recognizes a new diagnostic entity termed "other iatrogenic
      immunodeficiency-associated lymphoproliferative disorders" highlighting lymphomas
      arising in patients treated with immunosuppressive agents for autoimmune
      disorders. The role of antitumor necrosis factor alpha therapy (anti-TNFalpha)
      and lymphoma risk in rheumatoid arthritis (RA) patients remains unclear;
      therefore, the goal of our study was to determine whether anti-TNFalpha therapy
      is associated with iatrogenic lymphomas. A meta-analysis of all randomized
      controlled clinical trials published (2000-2009) in RA patients receiving anti
      TNFalpha therapy was performed. Fourteen studies fulfilled all search criteria
      and included 2,306 control patients and 5,179 patients treated with anti-TNFalpha
      therapy, namely etanercept, adalumimab, and infliximab. Clinical information
      including the number of patients, age, gender, lymphoma rates, and follow-up time
      was recorded. The overall rate and rate differences were analyzed using the
      DerSimonian and Laird method. Of the control group, four (4/2,306, 0.17%)
      patients developed hematolymphoid neoplasms. Eleven (11/5,179, 0.21%) patients
      receiving anti-TNFalpha therapy developed lymphomas. The adjusted overall rates
      are 0.36 lymphomas per 1,000 person-years in patients who did not receive anti
      TNFalpha therapy versus 1.65 lymphomas per 1,000 person-years in patients who
      received anti-TNFalpha therapy. The corresponding 95% confidence interval for
      this rate difference is (-0.214, 2.79). The adjusted rate difference is 1.29
      lymphomas per 1,000 person-years (95% CI, -0.21, 2.8; p value = 0.093). The
      corresponding p value is p = 0.0928. There is a suggestion of increased lymphomas
      in the treated group, with the predominant subset being B-cell lymphomas. Since
      the outcome of lymphoma is rare, it does not reach statistical significance of p
      < 0.05.

PMID- 22147208
TI  - Assessment of technical and biological parameters of volumetric quantitative
      computed tomography of the foot: a phantom study.
AB  - SUMMARY: Few studies exist for bone densitometry of the whole foot. A phantom
      study demonstrated the sources of error and necessary controls for accurate
      quantitative computed tomography of the foot. A loss in bone mineral density
      (BMD) in the small foot bones may be an early indicator of diabetic foot
      complications. INTRODUCTION: Volumetric quantitative computed tomography (vQCT)
      facilitates the assessment of pedal bone osteopenia, which, in the presence of
      peripheral neuropathy, may well be an early sign of diabetic foot deformity. To
      date, sources and magnitudes of error in foot vQCT measurements have not been
      reported. METHODS: Foot phantoms were scanned using a 64-slice CT scanner. Energy
      (in kilovoltage peak), table height, phantom size and orientation, location of
      "bone" inserts, insert material, location of calibration phantom, and
      reconstruction kernel were systematically varied during scan acquisition.
      RESULTS: Energy (in kilovoltage peak) and distance from the isocenter (table
      height) resulted in relative attenuation changes from -5% to 22% and -5% to 0%,
      respectively, and average BMD changes from -0.9% to 0.0% and -1.1% to 0.3%,
      respectively, compared to a baseline 120-kVp scan performed at the isocenter. BMD
      compared to manufacturer-specified values ranged, on average, from -2.2% to 0.9%.
      Phantom size and location of bone-equivalent material inserts resulted in
      relative attenuation changes of -1.2% to 1.4% compared to the medium-sized
      phantom. CONCLUSION: This study demonstrated that variations in kilovoltage peak
      and table height can be controlled using a calibration phantom scanned at the
      same energy and height as a foot phantom; however, error due to soft tissue
      thickness and location of bones within a foot cannot be controlled using a
      calibration phantom alone.

PMID- 22147209
TI  - Volumetric bone mineral density at the spine and hip in Chinese American and
      White women.
AB  - This study evaluated racial differences in bone size and volumetric density at
      the spine and hip in pre- and postmenopausal Chinese American and White women.
      Compared with White women, Chinese American women have greater cortical
      volumetric bone density (vBMD) at the hip, congruent with the results at the
      peripheral skeleton. INTRODUCTION: Chinese American women have lower rates of
      fracture than White women despite lower areal bone density. At the forearm and
      tibia, however, Chinese American women have higher cortical vBMD as well as
      greater trabecular and cortical thickness, but smaller bone area as measured by
      high-resolution peripheral quantitative computed tomography (HR-pQCT) compared
      with White women. Since HR-pQCT data are obtained at peripheral sites, it is
      unclear whether these differences are relevant to the clinically important lumbar
      spine and hip. This study assesses racial differences in bone size and vBMD at
      the spine and hip in Chinese American and White women. METHODS: QCT of the spine
      and hip was measured to assess racial differences in bone size, structure, and
      vBMD in pre- (n = 83) and postmenopausal (n = 50) Chinese American and White
      women. Data were adjusted for weight, height, physical activity, total calcium
      intake, parathyroid hormone, and 25-hydroxyvitamin D levels. RESULTS: Among
      premenopausal women, lumbar spine trabecular vBMD was 5.8% greater in Chinese
      American versus White women (p = 0.01). At the hip, cortical vBMD was 3% greater
      at the femoral neck (p = 0.05) and 3.6% greater at the total hip (p = 0.01) in
      premenopausal Chinese American compared with White women. Among postmenopausal
      women, there was no difference in lumbar spine trabecular vBMD. Cortical vBMD was
      4% greater at the total hip (p = 0.02) and tended to be greater at the femoral
      neck (p = 0.058) in Chinese American versus White women. CONCLUSIONS: Consistent
      with earlier findings in the peripheral skeleton, cortical vBMD is greater at the
      hip in Chinese American versus White women.

PMID- 22147210
TI  - Radiologic case study.

PMID- 22147211
TI  - Biomedical research and industry influence: some jasmine thoughts.

PMID- 22147212
TI  - Intraoperative fabrication of bone tamps for indirect reduction of depressed
      articular segments.
AB  - The use of bone tamps for indirect reduction of depressed articular segments is
      an established method of treatment for intra-articular fractures in a variety of
      joint injuries. Customized bone tamps can be fabricated intraoperatively using
      commonly available instruments and supplies consisting of Steinmann pins and T
      handled chucks. The technique combines the use of bone tamps through carefully
      created metaphyseal windows, fluoroscopic guidance, packing with cancellous bone,
      and adequate fixation. This treatment methodology can allow for a minimally
      invasive or soft tissue preserving approach for the treatment of some intra
      articular fractures while achieving anatomic reduction of the joint surface.

PMID- 22147213
TI  - Total hip arthroplasty.

PMID- 22147214
TI  - iPad apps for orthopedic surgeons.
AB  - The development and distribution of mobile applications, or apps, designed for
      medical professionals and patients is quickly expanding, and within this group
      are apps designed specifically for orthopedic use. Currently, the most popular
      mobile apps are sponsored by private companies and focus on delivering device
      specific information. If this trend toward the use of privately funded
      educational materials continues, regulations may need to be established to ensure
      that the information provided is accurate, honest, and supported by peer-reviewed
      literature. It will likely be the responsibility of the orthopedic community to
      ensure that the development and use of these apps has appropriate oversight and
      validation as they are incorporated into clinical practice and training.

PMID- 22147215
TI  - Update on the pharmacological prevention of skeletal-related events in cancer
      patients.
AB  - Metastases to the bone are a frequent complication of advanced cancer. Bone
      metastases have been linked to skeletal-related events, which is the composite
      endpoint used in clinical trials evaluating therapy to minimize these
      complications. This article discusses bisphosphonates, which are the historical
      standard for the prevention of skeletal-related events in patients with
      metastases from solid tumors and multiple myeloma, and denosumab, which is the
      first Food and Drug Administration-approved receptor activator of nuclear factor
      kappa-beta ligand (RANKL) inhibitor.

PMID- 22147216
TI  - Posterior horn medial meniscal root repair with cruciate ligament/medial
      collateral ligament combined injuries.
AB  - Many meniscal root tears remain unrepaired, potentially due to under-recognition
      and the technical challenge of repairing them. A great effort is made to preserve
      the native meniscus and restore the circumferential fibers for hoop stress
      resistance. It has been well demonstrated in the literature that failure to
      repair this will lead to increased contact pressures in the medial compartment
      and early degenerative changes in the articular cartilage. Our technique is one
      that allows the meniscus to resume its important role of knee stability. A
      thorough understanding of meniscal root anatomy, as well as repair techniques, is
      important for the cruciate ligament surgeon.

PMID- 22147218
TI  - Infected tumor prostheses.
AB  - Infection of tumor prostheses has been a major concern because of the extensive
      soft tissue dissection, long operating times, and patients' immunosuppression by
      cancer and adjuvant treatments. Infections most often present within 2 years
      postoperatively, with approximately 70% of postoperative deep infections
      presenting within 12 months after surgery. They are typically low organism burden
      infections, the pathogenesis of which is related to bacteria growing in biofilms.
      Staphylococci are the most common pathogens involved in prosthetic joint
      infections, accounting for approximately 50% of infections overall, followed by
      streptococci, enterococci, Enterobacteriaceae species, Pseudomonas aeruginosa,
      and anaerobe species. Multiple pathogens may be isolated in approximately 25% of
      cases, with the most common combination being coagulase-negative Staphylococcus
      and group-D Streptococcus. Early diagnosis and appropriate treatment are
      necessary. However, diagnosis may be challenging because clinical symptoms are
      highly variable and numerous preoperative and intraoperative diagnostic
      laboratory tests are nonspecific. In most cases, a 1- or 2-stage revision surgery
      is necessary for eradicating the megaprosthetic infection. Prevention of
      infection is important. The future will see technical advances for infections of
      tumor prostheses in areas such as microbiological diagnostics and biofilm
      resistant prostheses.

PMID- 22147221
TI  - Sensory cancellation of self-movement facilitates visual motion detection.
AB  - The nervous system continuously predicts the sensory consequences of self
      generated actions. These predictions can be used to cancel self-generated sensory
      information. It has been hypothesized that this cancellation process may serve to
      increase the perceptual sensitivity to unpredicted external events. Here, we
      provide the first empirical evidence for this idea. Participants were required to
      detect coherent motion in a random dot motion display. The task was made more
      difficult by a set of superimposed distractor dots that had to be ignored. When
      these distractors moved congruently with an active arm movement, perceptual
      performance in detecting the coherent motion was superior compared to a condition
      in which the distractor motion did not match the arm movement. To test whether
      this difference was due to sensory cancellation of matching distractors, or to
      the attentional enhancement of non-matching distractors, we introduced a control
      condition without any overt movement. Our results indicate that improvements in
      the detection of visual motion are indeed caused by sensory cancellation of self
      generated events. In conjunction with other recent results, our data therefore
      suggest that the nervous system is able to attenuate or facilitate self-generated
      visual stimuli in a task-dependent manner.

PMID- 22147222
TI  - Impaired visual decision-making in individuals with amblyopia.
AB  - This study examined the effects of amblyopia on perceptual decision-making
      processes to determine the consequences of visual deprivation on the development
      of higher level cortical networks outside of the visual cortex. A variant of the
      Eriksen flanker task was used to measure response time and accuracy for decisions
      made in the presence of response-selection conflict. Performance of adults with
      amblyopia was compared to that of neurotypical participants of the same age.
      Additionally, simple and choice reaction time tasks presented in the visual and
      the auditory modality were used to control for factors such as feature
      visibility, crowding, and motor execution speed. A selective deficit in response
      time for visual decisions was found when individuals with amblyopia used either
      the amblyopic or non-amblyopic (dominant) eye, and this deficit was independent
      of visual acuity, motor time, and performance accuracy. In trial conditions that
      provoked response-selection conflict, responses were significantly delayed in
      amblyopic relative to neurotypical participants and were not subject to standard
      trial sequence effects. Our results indicate that, beyond the known effects of
      abnormal visual experience on visual cortex, suboptimal binocular input during a
      developmental critical period may also impact cortical connections to downstream
      areas of the brain, including parietal and frontal cortices, that are believed to
      underlie decision and response-selection processes.

PMID- 22147223
TI  - Alcohol-induced psychotic disorder: brain perfusion and psychopathology--before
      and after anti-psychotic treatment.
AB  - Alcohol-induced psychotic disorder (AIPD) also known as alcohol hallucinosis is a
      rare complication of alcohol abuse. The pathogenesis and treatment of AIPD are
      still unclear. Few prospective treatment studies are available but case reports
      generally suggest that anti-psychotic treatment is effective. Brain imaging
      changes in relation to treatment response have also not been studied except for
      case reports. The aim of this study was to investigate the effect of anti
      psychotic treatment on psychopathology and regional cerebral blood flow (rCBF) in
      patients with AIPD before and after 6 weeks of treatment. Nineteen patients with
      AIPD were assessed by the Positive and Negative Syndrome Scale (PANSS) and single
      photon emission computed tomography (SPECT) before and after 6-weeks of open
      label treatment with a fixed dose of haloperidol (5 mg/day). Highly significant
      improvements were noted on the positive, general and total scores of the PANSS.
      Post-treatment increased rCBF to the left caudate and left frontal lobe was
      noted. Changes in frontal, temporal, parietal, occipital, thalamic and cerebellar
      rCBF showed significant negative correlations with the degree of symptom
      improvement, suggesting dysfunction of these areas in AIPD. Psychopathological
      and rCBF findings suggest reversible generalised cerebral dysfunction in AIPD.

PMID- 22147224
TI  - Leaf-trait responses to irrigation of the endemic fog-oasis tree Myrcianthes
      ferreyrae: can a fog specialist benefit from regular watering?
AB  - Myrcianthes ferreyrae is an endemic, endangered species, with a small number of
      individuals located only in hyperarid, fog-oases known as lomas along the
      Peruvian desert in southern Peru, where fog is the main source of water.
      Following centuries of severe deforestation, reforestation with this native
      species was conducted in the Atiquipa lomas, Arequipa-Peru. On five slopes, five
      2-year-old seedlings were irrigated monthly with water trapped by raschel-mesh
      fog collectors, supplementing natural rainfall with 0, 20, 40, 60 and 80 mm
      month(-1) from February to August 2008. We measured plant growth, increment in
      basal diameter, height and five leaf traits: leaf mass area (LMA), leaf carbon
      isotope composition (delta(13)C), nitrogen per leaf area, total leaf carbon and
      stomatal density; which are indicative of the physiological changes resulting
      from increased water supply. Plant growth rates, estimated from the variation of
      either shoot basal diameter or maximum height, were highly correlated with total
      biomass. Only LMA and delta(13)C were higher in irrigated than in control plants,
      but we found no further differences among irrigation treatments. This threshold
      response suggests an on-off strategy fitted to exploit pulses of fog water, which
      are always limited in magnitude in comparison with natural rain. The absence of a
      differential response to increased water supply is in agreement with the low
      phenotypic plasticity expected in plants from very stressful environments. Our
      results have practical implications for reforestation projects, since irrigating
      with 20 mm per month is sufficient to achieve the full growth capacity of this
      species.

PMID- 22147226
TI  - Impact of the implantation of a new curriculum in the process of learning in a
      Faculty of Dentistry in Brazil.
AB  - The aim of the present study was to evaluate two dental curricula at a school of
      dentistry in southern Brazil. The study population included dentists trained in
      the last two classes of the institution's old curriculum (n = 98) and graduates
      of the first two classes of the new curriculum (n = 56). A questionnaire with
      open and closed questions was used for an overall evaluation of different aspects
      of the curricula, such as study methods, importance given to basic sciences,
      quality of theoretical and clinical guidance, perception about skills needed to
      perform different dental procedures, professional goals and an overall
      assessment. Students in the new curriculum reported more frequent use of the
      internet (69.6%) and scientific articles (50.0%). More importance was given to
      the basic sciences in the new curriculum. Graduates of the old curriculum alleged
      themselves to be more capable of both performing conventional (99%) and complex
      amalgam restorations (68.4%), as well as three-unit fixed prostheses (62.2%).
      Graduates of the new curriculum alleged higher capability with periodontal
      surgeries (48.2%), treatment of temporomandibular joint (TMJ) disorders (58.1%)
      and public health planning (78.6%). Regarding professional goals, the new
      curriculum was associated with an increase in the graduates' willingness to work
      in the public health system and to pursue an academic career. New curriculum
      graduates reported higher overall assessments regarding their educational, as
      well as theoretical and clinical, outcomes. A new curricular approach was
      associated with several changes from the perspective of the students.

PMID- 22147227
TI  - Effects of different surface treatments and accelerated artificial aging on the
      bond strength of composite resin repairs.
AB  - The purpose of the present study was to assess the bond strength of composite
      resin repairs subjected to different surface treatments and accelerated
      artificial aging. 192 cylindrical samples (CSs) were prepared and divided into 24
      groups (n = 8). Half of the CSs were stored in water for 24 h, and the other half
      were subjected to C-UV accelerated aging for non-metallic specimens. The
      treatments were phosphoric acid + silane + adhesive (PSA); phosphoric acid +
      adhesive (PA); diamond bur + phosphoric acid + silane + adhesive (DPSA); diamond
      bur + phosphoric acid + adhesive (DPA); air abrasion + phosphoric acid + silane +
      adhesive (APSA); and air abrasion + phosphoric acid + adhesive (APA). The repair
      was performed and the specimens were again aged as described above. A control
      group (n = 8) was established and did not receive any type of aging or surface
      treatment. The specimens were loaded to failure in shear mode with a crosshead
      speed of 0.5 mm/min until fracture. Data were analyzed by one-way ANOVA/Tukey's
      test (p < 0.05). No statistically significant differences were found among DPSA,
      DPA, APSA, APA, and the control group. The aged PSA and PA achieved low bonding
      values and were statistically different from the control group, whereas the non
      aged PSA and PA presented no statistically significant difference from the
      control group. Repairs with the proposed surface treatments were viable on both
      recent and aged restorations; however, phosphoric acid + adhesive alone were
      effective only on recent restorations.

PMID- 22147228
TI  - Effect of a cordless retraction paste material on implant surfaces: an in vitro
      study.
AB  - Cordless retraction paste material for gingival retraction in implant dentistry
      has recently become of interest to the clinician. However, few studies have been
      conducted on the use of retraction pastes and their possible interaction with
      implant surfaces. This in vitro study evaluated the effect of a cordless
      retraction paste material, Expasyl(r) (Acteon), on TiUnite(r) (Nobel Biocare)
      implant surfaces. Three areas of the fixtures were evaluated before and after
      contact with the retraction paste using scanning electron microscopy to evaluate
      changes in surface topography and energy-dispersive spectroscopy to identify any
      surface chemistry modifications. Alteration of the initial surface after exposure
      to Expasyl(r) was identified, with the implant collar showing the most changes.

PMID- 22147229
TI  - Effect of titanium surface on secretion of IL1beta and TGFbeta1 by mononuclear
      cells.
AB  - Mononuclear cells play an important role in the modulation of healing. The
      characteristics of implant surface topography may alter the production of
      signaling molecules such as cytokines. The aim of this in vitro study was to
      evaluate the effects of commercially available titanium surface treatments on
      both cell viability and the secretion of the antagonist cytokines, IL1beta and
      TGFbeta1. Human mononuclear cells were cultured on 10 mm diameter commercially
      pure titanium (cpTi) disks that were prepared using a turning procedure (control
      = machined surface) and either acid etched or bio-anodized for 1-7 days. Adhered
      cells were investigated with respect to cell viability using an MTT assay, and
      cytokine production was verified using an ELISA assay. The results indicate that
      surface characteristics did not alter the cell viability at days 1 and 4,
      although the machined surface presented the highest absorbance values at day 7 (p
      = 0.0084). Cell viability was reduced throughout the time course for all analyzed
      surfaces (p < 0.05). On day 4, IL1beta levels were significantly higher on bio
      anodized compared to acid etched surfaces (p = 0.0097). TGFbeta1 did not show
      differences among the surfaces at days 1 and 4. The responses of non-stimulated
      mononuclear cells to titanium surfaces suggest only modest effects of the surface
      treatment and roughness on pro-inflammatory cytokine (IL1beta) release.

PMID- 22147230
TI  - Effect of occlusal splint thickness on electrical masticatory muscle activity
      during rest and clenching.
AB  - The extent of separation between the maxillary and mandibular teeth in the
      fabrication of interocclusal splints designed to achieve efficiency and muscle
      relaxation is controversial and undefined in the literature. Based on this
      premise, the aim of this study was to evaluate the effect of interocclusal splint
      thicknesses of 3 and 6 millimeters on the electrical activity of the anterior
      temporal and masseter muscles during rest and dental clenching. Twenty
      asymptomatic individuals (10 males and 10 females) were selected using the
      Research Diagnostic Criteria (RDC). Electromyography (EMG) was performed both
      with and without the 3- and 6-mm splints using the Bio EMG software package,
      which recorded values given in microvolts (uV). The results, which were assessed
      using analysis of variance (ANOVA) to a 5% significance level (p < 0.05), showed
      increased electrical activity of the masticatory muscles during dental clenching
      compared with at rest, with greater activity in the masseter muscle. The
      electrical activity did not differ according to the thickness of the splints or
      between males and females. We can conclude that both splint thicknesses are
      effective in treating muscle hyperactivity given their similar clinical behavior
      for asymptomatic individuals.

PMID- 22147231
TI  - Oral cancer staging established by magnetic resonance imaging.
AB  - The aim of this study was to compare clinical staging and magnetic resonance
      imaging (MRI) staging for oral cancer, and to assess inter-observer agreement
      between oral and medical radiologists. A total of 10 patients diagnosed with oral
      cancer were assessed before treatment. A head and neck surgeon performed clinical
      TNM staging. Two medical radiologists and two oral radiologists performed a new
      staging assessment by interpreting MRI scans, without prior knowledge of the
      clinical staging. They evaluated the extent of the primary tumor (T), metastasis
      to regional lymph nodes (N) and grouping by stages. The data were analyzed using
      the Kappa Index. There was significant agreement (p < 0.05) between the clinical
      and MRI staging assessments made by one oral radiologist for N stage, and between
      those made by one medical radiologist for the T and N stages and for the grouping
      by stages. In the MRI assessment, there was significant agreement among all four
      observers for both T stage and grouping by stages. For the N stage, there was no
      significant agreement between one oral radiologist and one medical radiologist or
      between both medical radiologists. There was significant agreement among the
      remaining radiologists. There was no agreement between the clinical and MRI
      staging. These results indicate the importance of using MRI for the diagnosis of
      oral cancer. Training initiatives and calibration of medical and oral
      radiologists should be promoted to provide an improved multidisciplinary approach
      to oral cancer.

PMID- 22147232
TI  - In vitro cytotoxic effects of Brazilian plant extracts on squamous cell carcinoma
      of the oral cavity.
AB  - Squamous cell carcinoma (SCC) is the most prevalent cancer of the oral cavity and
      the fifth most prevalent of all malignancies in males. Many researchers have
      attempted to develop new treatments that will improve the prognosis of SCC
      patients. Over 20% of the world's biodiversity is located within the Brazilian
      forests, but little is known about the chemical and/or pharmacological potential
      of these plants. Certain extracts obtained from Amazon and Atlantic Forest plants
      have previously been shown to have cytotoxic activity against various cancers.
      The aim of this study was to screen these extracts for cytotoxic activity against
      oral SCC cells. The extracts were analyzed for activity against the KB-ADL#12
      cell line at various concentrations up to a maximum dose of 100 ug/mL.
      Comparisons with a control group were performed using one-way ANOVA. Significant
      cytotoxicity was induced by the extracts obtained from the aerial parts of
      Picrolemma sprucei (Simaroubaceae), from the leaves and stems of Laetia
      suaveolens (Salicaceae), from the aerial parts of Abarema auriculata (Fabaceae
      Mimosoideae) and from the stem of A. auriculata.

PMID- 22147233
TI  - Frictional resistance of orthodontic wires tied with 3 types of elastomeric
      ligatures.
AB  - The aims of this study were to determine and compare frictional resistance
      obtained by low-friction and conventional elastomeric ligatures in the presence
      of artificial saliva, and observe whether this variable changed after 21 days.
      Super Slick(r) low-friction elastomeric ligatures and conventional ligatures of
      the brands TP conventional(r) and Unitek(r) were placed on standard edgewise
      maxillary central incisor metal brackets, slot .022" * .028" tying rectangular
      orthodontic wires .018" * .025". Three experimental groups were arranged
      according to the type of ligature and a control group in which no wires were
      used. The friction values obtained between the bracket/wire/ligature set were
      measured using a Universal Test Machine at a speed of 20 mm/minute, at two
      experimental time intervals: T0 - immediately after specimen fabrication; and T1 
      21 days after fabrication and immersion in artificial saliva at 37 oC.
      Conventional Unitek ligatures and the low-friction ligature (Super Slick) showed
      the lowest friction values at T0. After 21 days (T1), however, conventional
      Unitek ligatures presented the lowest value. All groups assessed from T0 to T1
      showed a numerical reduction in friction values, suggesting that time, heat and
      humidity may cause elastic degradation, however this was not verified
      statistically (P > 0.05).

PMID- 22147234
TI  - Developmental enamel defects and their impact on child oral health-related
      quality of life.
AB  - This cross-sectional study assessed the impact of Developmental Enamel Defects
      (DED) on Child Oral Health-Related Quality of Life (COHRQoL). A sample of 944 11-
      to 14-year-old Brazilian schoolchildren was examined for the prevalence and
      severity of DED. The children completed the Child Perceptions Questionnaire
      (CPQ11-14), and socioeconomic status was also collected using a questionnaire.
      Poisson regression models were used to assess the association between DED and
      overall and domain-specific CPQ11-14 scores. The prevalence of DED was 19.7%. In
      general, children with DED did not indicate any decrease in self-perception.
      However, this condition was associated with an impact on the functional
      limitation domain. The presence of DED may cause negative impacts on a child's
      perception of oral health and on their daily performance.

PMID- 22147235
TI  - Influence of different durations of estrogen deficiency on alveolar bone loss in
      rats.
AB  - The purpose of this study was to morphometrically evaluate the influence of
      different durations of ovariectomy-induced estrogen deficiency on alveolar bone
      loss associated with ligature-induced bone loss in rats. Sixty female Wistar rats
      were randomly assigned to ovariectomy (OVX test group) or sham operation (SHAM
      control group). The OVX and SHAM groups were each distributed into three
      subgroups of ten rats each according to the duration of estrogen deficiency (30,
      60 and 90 postoperative days). In all groups, for the last 30 days of the
      experimental period, cotton ligatures were placed around the cervix of the right
      upper second molar; the contralateral tooth was left unligated to serve as a
      control. The maxillary bones were removed, and the alveolar bone loss was
      analyzed by measuring the distance between the cementoenamel junction and the
      alveolar bone crest at the buccal site of the right upper second molar. A
      comparison between the ligated and unligated groups verified the presence of
      ligature-induced alveolar bone loss (p < 0.05). No significant differences were
      observed among the unligated groups (p > 0.05). A significant increase in bone
      loss was observed when ligation occurred 90 days after ovariectomy compared with
      the sham group (p < 0.05). These results demonstrate that long-term estrogen
      deficiency affects ligature-induced alveolar bone loss.

PMID- 22147237
TI  - Salivary IgA and periodontal treatment needs in diabetic patients.
AB  - Salivary IgA can serve as a first line of defense against pathogens that colonize
      and invade mucosal surfaces and may be protective against periodontal disease.
      The aim of this study was to assess salivary immunoglobulin A levels in diabetic
      and non-diabetic patients with different periodontal treatment needs. The
      Periodontal Screening & Recording (PSR) system was used to evaluate the
      periodontal treatment needs of 41 diabetic and 42 non-diabetic patients.
      Unstimulated whole saliva was collected from each patient immediately before
      clinical examination and stored at -20  degrees C until analysis. Salivary
      immunoglobulin A (s-IgA) levels were determined using an enzyme-linked
      immunosorbent assay, and values were expressed as optical density. Diabetic and
      non-diabetic patients were compared using clinical and laboratory data. PSR data
      indicated that periodontal disease was more frequent and more severe in diabetic
      patients. A higher prevalence of codes 3 and 4 was observed in diabetics as
      compared with non-diabetics (odds ratio = 2, P < 0.05). Furthermore, non-diabetic
      patients had more healthy sextants (code 0) than did diabetic patients. Over half
      of diabetic patients (~54%) presented with s-IgA levels that were lower than the
      normal range (optical density from 0.4 nm to 0.6 nm; P < 0.05). In addition,
      diabetic patients showed a higher variability in s-IgA levels as compared with
      non-diabetic patients. In conclusion, diabetic individuals had lower s-IgA
      levels, more-frequent and more-severe periodontal disease, and a greater need for
      periodontal treatment as compared with non-diabetic patients.

PMID- 22147236
TI  - Gingival inflammation and platelet count in patients with leukemia: preliminary
      results.
AB  - Leukemia has been associated with oral manifestations. However, the available
      literature on this topic consists of mostly reports of cases, without data about
      the periodontal parameters that may be under the influence of hematologic
      factors. The aim of this cross-sectional study was to assess the correlation
      between the Gingival Index and Bleeding on Probing with the platelet count in
      patients with leukemia. Patients with diagnosis of any kind of leukemia, at any
      stage of treatment, having a minimum age of 14 years, treated at the Department
      of Hematology-Oncology of the University Hospital of Santa Maria, Brazil, between
      December 2009 and March 2010, were assessed. Excluded patients were: edentulous,
      with orthodontic appliances, with psychomotor disturbances, requiring antibiotic
      prophylaxis for the examinations, or those using medications associated with
      gingival swelling. Two trained and calibrated examiners evaluated the Plaque
      Index, Gingival Index (GI), Probing depth, Bleeding on Probing (BOP), and
      Clinical Attachment Loss. Hematologic data were collected from a blood test
      performed on the same day as the periodontal examination. Thirty-seven patients
      (26 males), aged between 15 and 80 years (mean age 41.7 +/- 18.31) were
      evaluated. Correlation between platelet count and BOP (p > 0.05), or between
      platelet count and GI (p > 0.05), were both weak (Pearson's correlation
      coefficient r = 0.171 and r = -0.003, respectively) and not statistically
      significant. It can be concluded from the preliminary results that the low
      platelet count was not correlated with the higher prevalence of gingival and
      periodontal bleeding in patients with leukemia.

PMID- 22147238
TI  - Effect of vegetable oil (Brazil nut oil) and mineral oil (liquid petrolatum) on
      dental biofilm control.
AB  - Dental biofilm control represents a basic procedure to prevent caries and the
      occurrence of periodontal diseases. Currently, toothbrushes and dentifrices are
      used almost universally, and the employment of good oral hygiene allows for
      appropriate biofilm removal by both mechanical and chemical control. The aim of
      this study was to evaluate the effectiveness of adding vegetable or mineral oil
      to a commercially available dentifrice in dental biofilm control. A comparison
      using the Oral Hygiene Index Simplified (OHI-S) was performed in 30 individuals
      who were randomly divided into three groups. Group 1 (G1) received a commercially
      available dentifrice; the composition of this dentifrice was modified by addition
      of mineral oil (Nujol(r)) for group 2 (G2) or a vegetable oil (Alpha Care(r)) for
      group 3 (G3) at 10% of the total volume, respectively. The two-way repeated
      measures analysis of variance (two-way ANOVA) was used to test the effect of
      group (G1, G2 and G3) or time (baseline, 45 days and 90 days) on the OHI-S index
      scores. Statistical analysis revealed a significant reduction in the OHI-S at day
      90 in G2 (p < 0.05) and G3 (p < 0.0001) in comparison to G1. Therefore, the
      addition of a vegetable or a mineral oil to a commercially available dentifrice
      improved dental biofilm control, suggesting that these oils may aid in the
      prevention and/or control of caries and periodontal disease.

PMID- 22147239
TI  - In vitro evaluation of the microhardness of bovine enamel exposed to acid
      solutions after bleaching.
AB  - Acid erosion is a superficial loss of enamel caused by chemical processes that do
      not involve bacteria. Intrinsic and extrinsic factors, such as the presence of
      acid substances in the oral cavity, may cause a pH reduction, thus potentially
      increasing acid erosion. The aim of this study was to evaluate the microhardness
      of bleached and unbleached bovine enamel after immersion in a soda beverage,
      artificial powder juice and hydrochloric acid. The results obtained for the
      variables of exposure time, acid solution and substrate condition (bleached or
      unbleached enamel) were statistically analyzed by the ANOVA and Tukey tests. It
      was concluded that a decrease in microhardness renders dental structures more
      susceptible to erosion and mineral loss, and that teeth left unbleached show
      higher values of microhardness compared to bleached teeth.

PMID- 22147240
TI  - Microsurgical fenestration of retrocerebellar cysts as a treatment for
      syringomyelia.

PMID- 22147241
TI  - Graphene decoration with metal nanoparticles: towards easy integration for
      sensing applications.
AB  - A simple and versatile method for the decoration of CVD grown graphene with metal
      nanoparticles is presented. The mechanism of nanoparticle formation is galvanic
      displacement resulting in physically adsorbed clusters. The single layer graphene
      obtained by this method can be easily transferred. Integration onto a gas sensing
      transducer is presented as proof of concept.

PMID- 22147242
TI  - Late-life depressive symptoms: an international study.
AB  - OBJECTIVES: Evaluate differences in depressive symptoms, compare sociodemographic
      and health-related variables associated with depressive symptoms and report level
      of impact of depressive symptoms on daily activities. METHODS: Cross-sectional
      study using a self-administered questionnaire and Patient Health Questionnaire-9
      (PHQ-9) diagnostic survey on 1115 patients aged 60-93 years who attended a
      primary care clinic in Korea, Russia or USA. RESULTS: At least mild depression
      (PHQ-9 score of >= 5) occurred in 28% of Koreans, 65% of Russian and 27% of US
      participants. Russians scored more depressed on all PHQ-9 items (P < 0.01) and
      more suicidal thoughts (P < 0.001), while Koreans had less feelings of
      worthlessness (P < 0.001). Depression predictors included poorer self-rated
      health [odds ratio (OR) 2.47, 95% confidence interval (CI) 1.84-3.33, P <
      0.0001], chronic diseases (OR 1.34, CI 1.21-1.48, P < 0.0001), female gender (OR
      1.56, CI 1.15-2.12, P = 0.0046) and religious attendance (OR 0.88, CI 0.79-0.97,
      P = 0.0099) for all subjects. Being employed was protective in Korea (OR 0.41, CI
      0.21-0.77, P = 0.0061) and being married (OR 0.42, CI 0.27-0.66, P = 0.0002) and
      of older age (OR 0.95, CI 0.93-0.98, P = 0.0006) protective in US participants.
      Vascular disease was associated with depressive symptoms in Russia (OR 3.47, CI
      1.23-9.80, P = 0.0187). In regression analyses stratified by country for a given
      level of depressive symptoms, the Russian sample had less impact on daily
      activities (Russia R (2) = 0.107 versus Korea R (2) = 0.211 and US R (2) = 0.419)
      P = 0.029. CONCLUSIONS: Depressive symptoms were more common in Russia than in
      Korea and USA but had less impact on daily functioning. Cultural or environmental
      factors may account for this finding.

PMID- 22147243
TI  - Prevalence of colorectal polyps in pediatric colonoscopy.
AB  - BACKGROUND: The available data regarding the prevalence, types, and clinical
      determinants of colonic polyps in children is limited. AIMS: We aimed to estimate
      the prevalence of colorectal polyps in a large cohort of children. METHODS: We
      conducted a cross-sectional study to determine the presence, number, and location
      of colorectal polyps reported in all children (0-20 years) who underwent
      colonoscopy at 14 pediatric facilities between January 2000 and December 2007
      recorded in Pediatric Endoscopy Database System Clinical Outcomes Research
      Initiative (PEDS-CORI). We compared procedures with and without polyps with
      respect to procedure indication, age, sex, and race. We also reviewed a sample of
      histopathologic reports from one participating center. RESULTS: We analyzed
      13,115 colonoscopy procedures performed in 11,637 patients. Colorectal polyps
      were reported in 810 procedures (6.1%; 95% CI: 5.7-6.5%) performed in 705
      patients, and in 12% of patients with lower GI bleeding. Children with colorectal
      polyps were significantly younger (8.9 years vs. 11.9 years; p < 0.0001), male
      (58.3% vs. 49.0%; p < 0.001), non-white race (27.5% vs. 21.9%; p < 0.001), and
      had lower GI bleeding (54.4% vs. 26.6%; p < 0.001) as compared to children
      without polyps. In a sample of 122 patients with polyps from a single center, the
      histological types were solitary juvenile in 91 (70.5%), multiple juvenile in 20
      (15.5%), adenoma in 14 (10.9%) and hyperplastic polyps in four patients (3.1%).
      CONCLUSIONS: Colorectal polyps are detected in 6.1% overall and in 12.0% among
      those with lower gastrointestinal bleeding during pediatric colonoscopy.
      Approximately 26% are multiple juvenile or adenoma.

PMID- 22147244
TI  - Transjugular intrahepatic portosystemic shunt for portal cavernoma with
      symptomatic portal hypertension in non-cirrhotic patients.
AB  - BACKGROUND: Portal cavernoma is regarded as a contraindication to transjugular
      intrahepatic portosystemic shunt (TIPS). AIM: To evaluate the feasibility,
      safety, and efficacy of TIPS for symptomatic portal hypertension in non-cirrhotic
      patients with portal cavernoma. METHODS: Between July 2002 and December 2009, 46
      consecutive non-cirrhotic patients with portal cavernoma were admitted to our
      center. Twenty patients presented with variceal rebleeding (n = 20) and
      refractory ascites (n = 1), and were treated with TIPS. They were followed until
      either death or July 2010. Data were compared using the Fisher's exact test or t
      test. RESULTS: TIPS were successfully placed in 35% (7/20) of patients via a
      transjugular approach alone (n = 1), a combined transjugular/transhepatic
      approach (n = 4), and a combined transjugular/transsplenic approach (n = 2). TIPS
      were inserted in a large collateral vein in two patients in whom recanalization
      of the occluded main portal vein was impossible. Procedure-related complication
      was hepatic capsule perforation in one patient who was cured by medical therapy
      alone. Shunt dysfunction occurred in two patients, but TIPS revision was failed
      in one of them. Portosystemic pressure gradient was significantly reduced in TIPS
      success group (26.3 +/- 1.1 vs. 12.4 +/- 1.1 mmHg, p < 0.001). The incidence of
      variceal bleeding in TIPS success group is lower than that in TIPS failure group
      (14 vs. 69%, p = 0.057). In TIPS success group, two patients died of systemic
      infection and accident, respectively. In TIPS failure group, two patients died of
      liver failure. CONCLUSIONS: TIPS procedures are feasible and safe in selected
      patients with portal cavernoma. Successful TIPS insertions may decrease the
      incidence of variceal rebleeding.

PMID- 22147245
TI  - NOD2 polymorphism predicts response to treatment in Crohn's disease--first steps
      to a personalized therapy.
AB  - BACKGROUND AND AIMS: Great efforts have been made to predict disease behavior
      over time and the response to treatment in Crohn's disease (CD). Such
      understanding could personalize therapy. Early introduction of more aggressive
      therapies to patients at high risk and no introduction of predictable refractory
      treatments could become possible. We hence tested the influence of the NOD2
      carrier status on treatment response. PATIENTS AND METHODS: In 185 CD patients
      (age 45 +/- 9.8 years, female n = 108, minimum disease duration 10 years), the
      three most common polymorphisms (p.Arg702Trp, p.Gly908Arg, p.Leu1007fsX1008) of
      NOD2 were tested by polymerase chain reaction and sequencing. Detailed clinical
      and medical history were obtained with a standardized questionnaire and by
      reviewing the medical charts. Treatments introduced were chosen by physicians
      blinded to genotype data. RESULTS: The frequency of the NOD2 variant allele was
      about one-third (67, 30.2%) of CD patients. NOD2 carriers were more often treated
      with systemic and locally active steroids and with an immunosuppressant
      (Azathioprine/6-MP). NOD2 mutation carrier status was more often associated with
      systemic steroid [8.9% vs. wild-type (WT) 1.2%, P = 0.0086] and local-steroid
      refractory (14.9% vs. WT 3.5%; P = 0.001). The WT patients were significantly
      higher refractory to immunosuppressant (12.8% vs. NOD2 carriers, 0.5%, P = 0.03).
      Most WT patients were treated with TNF-alpha antagonists and remission rates were
      significantly higher in this group after 1 year of treatment (84% vs. NOD2
      carriers, 33%, P = 0.07). CONCLUSIONS: The study presents first hints for the
      NOD2 carrier status to be predictive for response to therapy. A higher percentage
      of CD patients with NOD2 mutation carrier status was steroid refractory but could
      be treated well with immunosuppressants. The WT status showed a higher response
      to steroids and remission rates within 1 year of anti-TNF-alpha therapy. On the
      way to personalized medicine, this approach should be further investigated in
      larger studies.

PMID- 22147246
TI  - Association between red cell distribution width and disease activity in patients
      with inflammatory bowel disease.
AB  - BACKGROUND: Recent studies have suggested that a higher red blood cell
      distribution width (RDW) is associated with disease activity in patients with
      inflammatory bowel disease (IBD). However, the RDW in IBD patients without anemia
      has not been investigated. AIM: This study aimed to determine whether or not RDW
      could be used for the assessment of disease activity in IBD patients with and
      without anemia. METHODS: The serum C-reactive protein (CRP) level, erythrocyte
      sedimentation rate (ESR), hemoglobin concentration, platelet and white blood cell
      counts, and RDW were assessed in 221 IBD patients, comprised of 120 patients with
      ulcerative colitis (UC) and 101 patients with Crohn's disease (CD). Disease
      activity was determined for UC and CD with the Mayo score and the Crohn's disease
      activity index, respectively. RESULTS: The CRP level, ESR, hemoglobin
      concentration, hematocrit, and RDW increased according to disease activity in
      patients with and without anemia (all P < 0.05). Multivariate analysis
      demonstrated that RDW was the best independent indicator for predicting disease
      activity in CD patients without anemia [odd ratios (OR), 1.702; 95% confidence
      interval (CI), 1.185-2.445; P = 0.004] and UC patients without anemia (OR, 4.921;
      95% CI, 2.281-10.615; P < 0.001). Also, ROC curve analysis showed the RDW to be
      the most significant indicator of non-anemic active IBD [area under curve (AUC)
      in CD, 0.852, P < 0.001; AUC in UC, 0.827, P < 0.001]. CONCLUSION: The
      association between increased RDW and active IBD was evident in IBD patients with
      and without anemia.

PMID- 22147247
TI  - Emu oil increases colonic crypt depth in a rat model of ulcerative colitis.
AB  - BACKGROUND: Current treatments for the inflammatory bowel diseases, encompassing
      Crohn's disease and ulcerative colitis, are variably effective. Emu oil,
      extracted from emu fat, predominantly comprises fatty acids, with purported
      claims of anti-inflammatory properties. AIM: We evaluated emu oil for its
      potential to ameliorate dextran sulphate sodium (DSS)-induced colitis in rats.
      METHODS: Male Sprague-Dawley Rats were allocated to treatment groups (n = 8).
      Groups 1 and 2 consumed water and were gavaged (1 ml) daily with water (group 1)
      or emu oil (group 2) from days 0 to 10. Groups 3-6 ingested 2% DSS in the
      drinking water from days 5 to 10 and were gavaged from days 0 to 10 with water
      (group 3), 0.5 ml emu oil (group 4) or 1 ml emu oil (group 5). Group 6 received 1
      ml emu oil after commencing DSS treatment (days 6-10). Disease activity index,
      metabolic parameters, (13)C-sucrose breath test, and histological colonic damage
      severity and crypt depth were assessed. RESULTS: Emu oil in DSS-treated rats
      reduced colonic damage severity compared to DSS-controls (up to threefold; P <
      0.001). In DSS-treated rats, crypts in the proximal colon were lengthened by 0.5
      ml emu oil (373 +/- 18 MUm), compared with DSS-controls (302 +/- 8 MUm); whilst
      in the distal colon (DSS control: 271 +/- 17 MUm), crypt depth was greater
      following 0.5 ml emu oil (352 +/- 22 MUm) and 1 ml emu oil (341 +/- 9 MUm) and
      also when emu oil was administered post-DSS commencement (Group 6: 409 +/- 16
      MUm; P < 0.05). Emu oil did not significantly affect other parameters of colonic
      architecture. CONCLUSIONS: Emu oil improved tissue damage associated with
      colitis, suggesting its potential as a unique formulation to augment conventional
      treatment approaches for IBD.

PMID- 22147248
TI  - Patients with inflammatory bowel disease have a lower response rate to HBV
      vaccination compared to controls.
AB  - BACKGROUND: Hepatitis B (HBV) is a vaccine-preventable infection that may cause
      severe infections, particularly in patients who are being treated with
      immunosuppressive therapy [(i.e., inflammatory bowel disease (IBD)]. Limited data
      are available about IBD patients' response rate to HBV vaccine. AIM: To assess
      the efficacy of HBV vaccine in IBD patients and healthy controls. METHODS:
      Serological markers of HBV were assessed in IBD patients, and HBV vaccine was
      administered to seronegative patients. The subsequent determination of anti-HBs
      antibody was recorded. An adequate immune response (AIR) and an effective immune
      response (EIR) to HBV were defined as more than 10 and 100 mIU/ml, respectively.
      The single dose vaccine was administered at 0, 1 and 6 months. RESULTS: A total
      of 102 patients with IBD (39 Crohn's disease, 63 ulcerative colitis; 54 female,
      48 male) and 52 (25 female, 27 male) healthy controls were included. Mean age for
      patients and controls were 38 +/- 12 and 31 +/- 8, respectively (P < 0.001). Both
      AIR and EIR were significantly lower in patients than in controls (P < 0.001),
      but they were similar between patients with CD and UC (P = 0.302). Forty-four
      (43%) patients were on immunosuppressive therapy before vaccination. After
      vaccination, 76 and 53% of the patients had AIRs and EIRs, respectively, whereas
      100 and 87% of the controls had AIRs and EIRs, respectively (P < 0.001 and P <
      0.001, respectively). CONCLUSIONS: The response rate of IBD patients receiving
      HBV vaccinations were significantly lower compared to controls. The response rate
      of those receiving immunosuppressive therapy and with active disease was much too
      low. Vaccination should be given during remission and at immunosuppression-free
      times.

PMID- 22147249
TI  - Outcome of repeat ERCP after initial failed use of a needle knife for biliary
      access.
AB  - INTRODUCTION: A needle knife is often used to gain bile duct access when standard
      techniques have failed. If unsuccessful, the next step may involve either
      radiological- or endoscopic ultrasound-guided biliary access. However, repeat
      endoscopic retrograde cholangiopancreatography (ERCP) may be an option if the
      patient's clinical condition permits. AIM: To determine the success of repeat
      ERCP after failed use of a needle knife to gain biliary access. METHODS:
      Retrospective analysis of all patients who underwent initial unsuccessful biliary
      cannulation after use of a needle knife between 2007 and 2010. RESULTS: Seventy
      five patients were identified. Of these, 51 (68%) underwent repeat ERCP, and
      biliary cannulation was successful in 38 (75%). The median time to repeat ERCP
      was 7.7 days (range 1-28 days). Complications developed in two (4%) patients.
      These included one case each of wire-guided perforation and mild pancreatitis,
      both of which were resolved by conservative management. CONCLUSIONS: Repeat ERCP
      within a few days after failed use of a needle knife for biliary access is
      associated with acceptable success and acceptable incidence of complications, and
      therefore obviates the need for alternative approaches for biliary access for
      most patients.

PMID- 22147250
TI  - Mapping analysis of ghrelin producing cells in the human stomach associated with
      chronic gastritis and early cancers.
AB  - OBJECTIVE: The majority of ghrelin producing cells (GPC) are present in the
      fundic gland of the stomach and recognized as X/A like cells. The detailed
      distribution of GPC in the stomach is still unknown in healthy and pathological
      subjects. METHODS: We investigated the detailed distribution of GPC in the
      stomach, especially in relation with chronic gastritis, using surgical specimens
      from 12 patients with early gastric cancer. Either the anterior or posterior half
      of the whole stomach, which was a counterpart of the tumor bearing side, was
      subjected for immunohistochemistry of ghrelin, and the number of total GPC were
      semi quantitatively evaluated as GPC score. GPC score was compared with the
      degree of chronic gastritis, serum ghrelin concentration and body weight.
      RESULTS: GPC was not observed in the pyloric gland, but heterogeneously
      distributed in the fundic gland mainly in upper body and the greater curvature.
      The GPC score showed about nine-fold difference, which correlated well with the
      degree of chronic gastritis by Sydney score (r = -0.84, P < 0.001). The serum
      ghrelin concentration was basically determined by the GPC score (r = 0.75, P =
      0.0047); however, the obese patients showed low serum ghrelin concentration in
      spite of the presence of abundant GPCs. In the low GPC score patients, serum
      ghrelin was constantly low regardless of their body weight. CONCLUSIONS: GPC was
      inversely correlated with progression of chronic gastritis. Its quantification
      using immunohistochemistry of the whole stomach was useful to comprehensively
      evaluate ghrelin profile.

PMID- 22147251
TI  - Increased expression of VEGF, COX-2, and Ki-67 in Barrett's esophagus: does the
      length matter?
AB  - BACKGROUND: Barrett's esophagus (BE) is a major complication of gastroesophageal
      reflux disease due to its neoplastic potential. The length of the metaplastic
      epithelium has been associated with cancer risk. Angiogenesis, inflammation, and
      increased cell proliferation are early events in the malignant sequence. Vascular
      endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and Ki-67 are indirect
      markers of these complex mechanisms. AIMS: To examine the expression of VEGF, COX
      2 and Ki-67 in BE and investigate whether there is an association to Barrett's
      length. METHODS: Immunohistochemistry for VEGF, COX-2, and Ki-67 was performed in
      well-characterized Barrett's samples, evaluated using a qualitative scale and
      compared between long (LSBE) and short (SSBE) segments. RESULTS: The study
      population consisted of 98 patients (78 men). LSBE and SSBE was diagnosed in 33
      (33.7%) and 65 (66.3%) cases, respectively. VEGF was expressed in vascular
      endothelium of all Barrett's specimens. COX-2 and Ki-67 expression in metaplastic
      epithelia was strong in 81.6 and 61.2% of the samples, respectively. Ki-67
      expression was significantly stronger in LSBE (p = 0.035), whereas VEGF
      expression was significantly increased in SSBE (p = 0.031). COX-2 expression was
      not associated with Barrett's length. CONCLUSIONS: VEGF, COX-2, and Ki-67 were
      overexpressed in the majority of Barrett's samples. The length was inversely
      associated with VEGF expression and directly associated with Ki-67 expression.

PMID- 22147252
TI  - Risk factors, clinical features, and prognosis of the hepatocellular carcinoma
      with peritoneal metastasis.
AB  - BACKGROUND: The clinical features and prognosis of hepatocellular carcinoma (HCC)
      with peritoneal metastasis have not been fully evaluated. AIMS: This study aimed
      to investigate the risk factors, clinical features, and prognosis of HCC with
      peritoneal metastasis. METHODS: Patients who were diagnosed as HCC with
      peritoneal metastasis and the same number of randomly selected, risk factor
      matched HCC controls without peritoneal metastasis were included. The risk
      factors and overall survival were compared between peritoneal metastasis-positive
      and -negative groups after adjustment of other variables. RESULTS: HCC rupture
      was an independent risk factor for peritoneal metastasis in HCC patients (P =
      0.008). When the risk factors (age, sex, Child-Pugh score, and intrahepatic tumor
      stage) were matched, peritoneal metastasis failed to independently affect overall
      survival (P = 0.511). In the peritoneal metastasis-positive group, advanced Child
      Pugh class [hazard ratio (HR), 1.99; 95% confidence interval (CI), 1.07-3.72; P =
      0.030] and progressive intrahepatic HCC status (HR, 19.04; 95% CI, 2.55-142.13; P
      = 0.004) were independent risk factors for early death. Complications such as
      ileus, bleeding, and hydronephrosis due to rectovesical mass were reported in 1.5
      7.4% in the peritoneal metastasis-positive group. CONCLUSIONS: Peritoneal
      metastasis was not found to be an independent prognostic factor of HCC, and among
      HCC patients with peritoneal metastasis, those with advanced Child-Pugh class and
      with uncontrolled intrahepatic HCC showed poor survival. Therefore, the
      maintenance of favorable hepatic function and control of intrahepatic HCC should
      still be emphasized in HCC patients with peritoneal metastasis.

PMID- 22147253
TI  - Math1/Atoh1 contributes to intestinalization of esophageal keratinocytes by
      inducing the expression of Muc2 and Keratin-20.
AB  - BACKGROUND: Esophageal intestinal metaplasia, also known as Barrett's esophagus,
      is the replacement of the normal epithelium with one that resembles the intestine
      morphologically. Generally, this includes intestinal mucin-secreting goblet
      cells. Barrett's esophagus is an important risk factor for adenocarcinoma
      development. In-vitro models for Barrett's esophagus have not, to date, focused
      on the induction of goblet cells in Barrett's epithelium. AIMS: To explore the
      contribution of Math1/Atoh1 to induction of Barrett's esophagus and intestinal
      mucin-secreting goblet cells from normal human esophageal epithelium. METHODS: We
      explored the level and pattern of Math1/Atoh1 mRNA and protein expression in
      human Barrett's esophagus. Then, using retroviral-mediated gene expression, we
      induced Math1 mRNA and protein expression in a human esophageal keratinocyte cell
      line. We evaluated the effects of this ectopic Math1 expression on cell
      proliferation and gene expression patterns in cells cultured under two
      dimensional and three-dimensional tissue-engineering conditions. RESULTS:
      Math1/Atoh1 mRNA and protein are detected in human Barrett's esophagus specimens,
      but the mRNA levels vary substantially. In the keratinocyte expression studies,
      we observed that Math1/Atoh1 ectopic expression significantly reduced cell
      proliferation and altered cell morphology. Moreover, Math1/Atoh1 expression is
      associated with a more intestinalized gene expression pattern that is distinct
      from that reported in after studies using other intestinal transcription factors.
      Most significantly, we observe the induction of the Barrett's esophagus markers
      Mucin-2 and Keratin-20 with Math1/Atoh1 expression. CONCLUSIONS: We conclude that
      ectopic Math1/Atoh1 expression makes unique contributions to intestinalization of
      the esophageal epithelium in Barrett's esophagus.

PMID- 22147254
TI  - Two brothers with skewed thiopurine metabolism in ulcerative colitis treated
      successfully with allopurinol and mercaptopurine dose reduction.
AB  - Thiopurine therapy effectively maintains remission in inflammatory bowel disease.
      However, many patients are unable to achieve optimum benefits from azathioprine
      or 6-mercaptopurine because of undesirable metabolism related to high thiopurine
      methyltransferase (TPMT) activity characterized by hepatic transaminitis
      secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced
      levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize
      this skewed metabolism. We discuss two brothers who were both diagnosed with
      ulcerative colitis (UC). Their disease remained active despite oral and topical
      mesalamines. Steroids followed by 6-mercaptopurine (MP) were unsuccessfully
      introduced for both patients and both were found to have high 6-MMP and low 6-TGN
      levels, despite normal TMPT enzyme activity, accompanied by transaminitis.
      Allopurinol was introduced in combination with MP dose reduction. For both
      brothers addition of allopurinol was associated with successful remission and
      optimized MP metabolites. These siblings with active UC illustrate that skewed
      thiopurine metabolism may occur despite normal TPMT enzyme activity and can lead
      to adverse events in the absence of disease control. We confirm previous data
      showing that addition of allopurinol can reverse this skewed metabolism, and
      reduce both hepatotoxicity and disease activity, but we now also introduce the
      concept of a family history of preferential MP metabolism as a clue to effective
      management for other family members.

PMID- 22147255
TI  - In vivo RNA interference of a gonad-specific transforming growth factor-beta in
      the Pacific oyster Crassostrea gigas.
AB  - We investigated the role of oyster gonadal TGFbeta (og-TGFbeta) in the
      reproduction of Crassostrea gigas, using an in vivo RNA interference approach. We
      designed double-stranded RNA targeting og-TGFbeta, which is specifically
      expressed in the somatic cells surrounding germ cells in the gonad of both male
      and female oysters. In vivo injection of this og-TGFbeta dsRNA into the gonad led
      to knock-down phenotypes for both sexes, with significant reduction (77.52%
      relative to controls) of the gonad area, lowered reproductive effort and germ
      cell under-proliferation. Interestingly, half of the injected females halted
      their vitellogenesis, since we were only able to observe pre-vitellogenic
      oocytes. In addition, apoptotic germ cells and haemocytes infiltrated into the
      gonad, likely as part of the active resorption of degenerating germ cells.
      Conversely, males showed a normal phenotype at the cellular level, with
      spermatids and spermatozoids observed in the gonads of control and injected
      males. As a result, og-TGFbeta appears to play an essential role in C. gigas germ
      cell development by functioning as an activator of germ cell proliferation in
      both male and female oysters and vitellogenesis in females.

PMID- 22147256
TI  - Examination of a role for metabotropic glutamate receptor 5 in the medial
      prefrontal cortex in cocaine sensitization in rats.
AB  - RATIONALE: Glutamatergic projection neurons in the medial prefrontal cortex
      (mPFC) are hyperexcitable in cocaine-sensitized animals, resulting in increased
      excitatory output to addiction-associated regions such as the ventral tegmental
      area (VTA) and nucleus accumbens. Evidence suggests that Group I metabotropic
      glutamate receptor 5 (mGluR5) is necessary for cocaine sensitization, and
      stimulation of this receptor in the mPFC potentially alters cell excitability
      directly through glutamate release or indirectly through downstream signaling
      cascades. OBJECTIVES AND METHODS: Experiments in this report examined the role of
      mPFC mGluR5 in behavioral sensitization to cocaine. Group I mGluR agonist
      dihydroxyphenylglycine (DHPG) (15 nmol/side), mGluR5 antagonist 3((2-methyl-4
      thiazolyl)ethynyl)pyridine (MTEP) (15 nmol/side), mGluR1 antagonist YM298198 (15
      nmol/side), AMPA receptor antagonist CNQX (1 nmol/side), and/or saline were
      administered through cannulae implanted 1 mm above the mPFC and/or VTA in male
      rats. Cocaine (15 mg/kg, i.p.) was systemically administered for four consecutive
      days to induce sensitization and/or once on test day immediately preceding
      locomotor monitoring. RESULTS: Intra-mPFC DHPG induced an mGluR5-mediated cross
      sensitization to cocaine preventable through the prior administration of an AMPA
      receptor antagonist in the VTA. Furthermore, mGluR5 blockade in the mPFC failed
      to prevent the initiation of sensitization. However, intra-mPFC injections of the
      mGluR5 antagonist MTEP prevented the expression of cocaine sensitization at 21,
      but not 7, days following daily cocaine injections suggesting a possible role for
      mPFC mGluR5 in the persistence of the cocaine-sensitized state. CONCLUSIONS:
      These data suggest that stimulation of mGluR5s in the mPFC is sufficient to
      induce cocaine sensitization and is necessary for the expression of this
      sensitized response.

PMID- 22147257
TI  - Effect of PDE10A inhibitors on MK-801-induced immobility in the forced swim test.
AB  - RATIONALE: Negative symptoms of schizophrenia are insufficiently treated by
      current antipsychotics. However, research is limited by the lack of validated
      models. Clinical data indicate that phencyclidine (PCP) abuse may induce symptoms
      resembling negative symptoms in humans. Based on that, Noda et al. proposed a
      model of PCP-induced increase of immobility in the forced swim test in mice as a
      model of depression-like negative symptoms of schizophrenia. OBJECTIVES: The aim
      of the study was to evaluate the effect of phosphodiesterase 10A (PDE10A)
      inhibition in this model which was modified by using MK-801 instead of PCP.
      METHODS: Increase of immobility in the forced swim test was induced by repeated
      MK-801 treatment followed by a 2-day washout in mice. The effect of haloperidol,
      clozapine, risperidone and PDE10A inhibitors was evaluated in this model, on open
      field activity and acute MK-801-induced hyperactivity. RESULTS: Repeated MK-801
      treatment significantly increased immobility in the forced swim test without
      affecting open-field activity. It induced hypersensitivity to the dopamine D1
      agonist A-68930, suggesting a hypofunction of the D1 pathway. The increase of
      immobility is reversed by clozapine and PDE10A inhibitors, but not by
      haloperidol. Clozapine and the PDE10A inhibitors did not enhance activity at
      effective doses. CONCLUSION: The possibility to substitute PCP by MK-801 in this
      model indicates that the effect is mediated by their common mechanism of NMDA
      antagonism. PDE10A inhibitors similar to clozapine significantly antagonize the
      increase of immobility, suggesting a therapeutic potential for the treatment of
      negative symptoms. However, further validation of the model is necessary.

PMID- 22147258
TI  - In vivo electrophysiological and neurochemical effects of the selective 5-HT1A
      receptor agonist, F13640, at pre- and postsynaptic 5-HT1A receptors in the rat.
AB  - RATIONALE: F13640 (befiradol) is a novel 5-HT(1A) receptor agonist with
      exceptional selectivity vs. other receptors and binding sites. It shows analgesic
      activity in animal models and is currently developed for human use. OBJECTIVES:
      Given the potential dual role of the serotonergic system in pain, through the
      modulation of ascending signals in spinal cord and their emotional processing by
      corticolimbic areas, we examined the in vivo activity of F13640 at
      somatodendritic autoreceptors and postsynaptic 5-HT(1A) heteroreceptors in medial
      prefrontal cortex (mPFC). METHODS: In vivo single unit recordings and
      intracerebral microdialysis in the rat. RESULTS: F13640 reduced the activity of
      dorsal raphe serotonergic neurons at 0.2-18.2 MUg kg(-1), i.v. (cumulative doses;
      ED(50) = 0.69 MUg kg(-1), i.v.) and increased the discharge rate of 80% of mPFC
      pyramidal neurons in the same dose range (ED(50) = 0.62 MUg kg(-1), i.v.). Both
      effects were reversed by the subsequent administration of the 5-HT(1A) receptor
      antagonist (+/-)WAY100635. In microdialysis studies, F13640 (0.04-0.63 mg kg(-1),
      i.p.) dose-dependently decreased extracellular 5-HT in the hippocampus and mPFC.
      Likewise, F13640 (0.01-2.5 mg kg(-1), i.p.) dose-dependently increased
      extracellular DA in mPFC, an effect dependent on the activation of postsynaptic 5
      HT(1A) receptors in mPFC. Local perfusion of F13640 in mPFC (1-1,000 MUM) also
      increased extracellular DA in a concentration-dependent manner. Both the systemic
      and local effects of F13640 were prevented by prior (+/-)WAY100635
      administration. CONCLUSIONS: These results indicate that, upon systemic
      administration, F13640 activates both 5-HT(1A) autoreceptors and postsynaptic 5
      HT(1A) receptors in prefrontal cortex with a similar potency. Both activities are
      likely involved in the analgesic properties of the compound.

PMID- 22147260
TI  - Genetic variants in oxidative stress-related genes predict chemoresistance in
      primary breast cancer: a prospective observational study and validation.
AB  - Chemotherapy response in patients with primary breast cancer is difficult to
      predict and the role of host genetic factors has not been thoroughly
      investigated. We hypothesized that polymorphisms in oxidative stress (OS)-related
      genes, including estrogen-quinone metabolizing enzymes NQO2 and GSTM1-5, may
      influence disease progression and treatment response. In this prospective
      observational study, nineteen polymorphisms tagging known variations in candidate
      genes were genotyped and analyzed in 806 patients with primary breast cancer.
      Three functional polymorphisms, which were shown to affect gene expression levels
      in experiments in vitro and ex vivo, modified the effect of chemotherapy on
      disease-free survival. There were significant interactions between chemotherapy
      and individual polymorphisms or combined genotypes (designated as genetic score).
      Patients harboring high genetic score had a 75% reduction in the hazard of
      disease progression compared with patients with low genetic score when no
      chemotherapy was administered (HR = 0.25, 95% CI: 0.10-0.63, P = 0.005); however,
      they received much less survival benefit from adjuvant chemotherapy compared with
      patients with low genetic score when chemotherapy was administered (HR = 4.60 for
      interaction, 95% CI: 1.63-13.3, P = 0.004). These findings were validated in
      another population (n = 339). In conclusion, germline polymorphisms in OS-related
      genes affect chemotherapy sensitivity in breast cancer patients. Although reduced
      OS levels might prevent breast cancer progression, they probably compromise the
      effectiveness of adjuvant chemotherapy. Our findings also indicate that host
      related factors must be considered for individualized chemotherapy.

PMID- 22147259
TI  - Involvement of metabotropic glutamate receptor 5 in brain reward deficits
      associated with cocaine and nicotine withdrawal and somatic signs of nicotine
      withdrawal.
AB  - RATIONALE: The involvement of metabotropic glutamate 5 (mGlu5) receptors has been
      suggested in the reinforcing effects of psychostimulants. However, little is
      known about the role of these receptors in psychostimulant withdrawal.
      OBJECTIVES: The role of mGlu5 receptors was assessed in the anhedonic and somatic
      aspects of psychostimulant withdrawal. METHODS: Anhedonia was assessed with the
      discrete-trial current-intensity intracranial self-stimulation (ICSS) procedure
      after the termination of cocaine (180 mg kg(-1) day(-1), salt, 3 days, i.p.) or
      nicotine (40 mg kg(-1) day(-1), base, 28 days, s.c.) administration via osmotic
      minipumps in mGlu5 receptor knockout (mGluR5(-/-)) and wild-type (mGluR5(+/+))
      mice. Somatic signs were assessed during nicotine withdrawal. The effects of the
      nicotinic acetylcholine receptor antagonist mecamylamine on ICSS thresholds were
      assessed during chronic nicotine administration. RESULTS: Nicotine-treated
      mGluR5(+/+) and mGluR5(-/-) mice demonstrated similar threshold elevations during
      mecamylamine-precipitated withdrawal compared with their saline-treated
      counterparts. During spontaneous nicotine and cocaine withdrawal, thresholds in
      drug-withdrawing mGluR5(+/+), but not mGluR5(-/-), mice were elevated up to 72 h
      of nicotine/cocaine withdrawal and then returned to baseline, indicating
      attenuation of withdrawal-induced anhedonia in mGluR5(-/-) mice. Nicotine
      withdrawing mGluR5(+/+), but not mGluR5(-/-), mice showed increases in somatic
      signs compared with saline-treated counterparts. CONCLUSIONS: mGlu5 receptor null
      mutation attenuates the anhedonic and somatic effects of psychostimulant
      withdrawal. This attenuated withdrawal in mGluR5(-/-) mice may result from the
      lack of drug-induced adaptations in mGlu5 receptor function that may occur in
      mGluR5(+/+) mice with chronic drug administration. Thus, these results suggest
      the involvement of mGlu5 receptors in psychostimulant dependence and the
      mediation of the anhedonic and somatic signs of psychostimulant withdrawal.

PMID- 22147261
TI  - Dysregulation of ezrin phosphorylation prevents metastasis and alters cellular
      metabolism in osteosarcoma.
AB  - Ezrin links the plasma membrane to the actin cytoskeleton where it plays a
      pivotal role in the metastatic progression of several human cancers; however, the
      precise mechanistic basis for its role remains unknown. Here, we define
      transitions between active (phosphorylated open) and inactive (dephosphorylated
      closed) forms of Ezrin that occur during metastatic progression in osteosarcoma.
      In our evaluation of these conformations we expressed C-terminal mutant forms of
      Ezrin that are open (phosphomimetic T567D) or closed (phosphodeficient T567A) and
      compared their biologic characteristics to full-length wild-type Ezrin in
      osteosarcoma cells. Unexpectedly, cells expressing open, active Ezrin could form
      neither primary orthotopic tumors nor lung metastases. In contrast, cells
      expressing closed, inactive Ezrin were also deficient in metastasis but were
      unaffected in their capacity for primary tumor growth. By imaging single
      metastatic cells in the lung, we found that cells expressing either open or
      closed Ezrin displayed increased levels of apoptosis early after their arrival in
      the lung. Gene expression analysis suggested dysregulation of genes that are
      functionally linked to carbohydrate and amino acid metabolism. In particular,
      cells expressing closed, inactive Ezrin exhibited reduced lactate production and
      basal or ATP-dependent oxygen consumption. Collectively, our results suggest that
      dynamic regulation of Ezrin phosphorylation at amino acid T567 that controls
      structural transitions of this protein plays a pivotal role in tumor progression
      and metastasis, possibly in part by altering cellular metabolism.

PMID- 22147263
TI  - Spectrum of MTHFR gene SNPs C677T and A1298C: a study among 23 population groups
      of India.
AB  - Elevated homocysteine is a risk factor for many complex disorders. The role of
      methylenetetrahydrofolate reductase (MTHFR) gene in methylation of homocysteine
      makes it one of the most important candidate genes for these disorders.
      Considering the heterogeneity in its distribution in world populations, we
      screened MTHFR C677T and A1298C single nucleotide polymorphisms in a total of 23
      Indian caste, tribal and religious population groups from five geographical
      regions of India and belonging to four major linguistic groups. The frequencies
      of MTHFR 677T and 1298C alleles were found to be 10.08 and 20.66%, respectively.
      MTHFR homozygous genotype 677TT was absent in eight population groups and
      homozygous 1298CC was absent in two population groups. 677T allele was found to
      be highest among north Indian populations with Indo-European tongue and 1298C was
      high among Dravidian-speaking tribes of east India and south India. The less
      common mutant haplotype 677T-1298C was observed among seven population groups and
      overall the frequency of this haplotype was 0.008, which is similar to that of
      African populations. cis configuration of 677T and 1298C was 0.94%. However, we
      could not find any individual with four mutant alleles which supports the earlier
      observation that presence of more than two mutant alleles may decrease the
      viability of foetus and possibly be a selective disadvantage in the population.

PMID- 22147262
TI  - Identification of molecular vulnerabilities in human multiple myeloma cells by
      RNA interference lethality screening of the druggable genome.
AB  - Despite recent advances in targeted treatments for multiple myeloma, optimal
      molecular therapeutic targets have yet to be identified. To functionally identify
      critical molecular targets, we conducted a genome-scale lethality study in
      multiple myeloma cells using siRNAs. We validated the top 160 lethal hits with
      four siRNAs per gene in three multiple myeloma cell lines and two non-myeloma
      cell lines, cataloging a total of 57 potent multiple myeloma survival genes. We
      identified the Bcl2 family member MCL1 and several 26S proteasome subunits among
      the most important and selective multiple myeloma survival genes. These results
      provided biologic validation of our screening strategy. Other essential targets
      included genes involved in RNA splicing, ubiquitination, transcription,
      translation, and mitosis. Several of the multiple myeloma survival genes,
      especially MCL1, TNK2, CDK11, and WBSCR22, exhibited differential expression in
      primary plasma cells compared with other human primary somatic tissues. Overall,
      the most striking differential functional vulnerabilities between multiple
      myeloma and non-multiple myeloma cells were found to occur within the 20S
      proteasome subunits, MCL1, RRM1, USP8, and CKAP5. We propose that these genes
      should be investigated further as potential therapeutic targets in multiple
      myeloma.

PMID- 22147264
TI  - Advances in the laboratory evaluation of peripheral neuropathies.
AB  - Peripheral neuropathy is a common clinical problem in neurology and laboratory
      testing is an integral part of diagnosis. In the past few years, practice
      parameters have been published to establish an evidence-based guide to neuropathy
      testing. There are many tests that are common and accepted in practice, but there
      is no clear mandate on which tests are necessary. This article reviews recent
      practice parameter publications as well as other updates in laboratory testing
      for peripheral neuropathy, including the roles of lipid profile, genetic testing,
      antibody titers, and B(12) testing in a specific dopamine-treated Parkinson's
      patients. These can serve as recommendations to help guide laboratory testing.

PMID- 22147266
TI  - Analysis of early C2C12 myogenesis identifies stably and differentially expressed
      transcriptional regulators whose knock-down inhibits myoblast differentiation.
AB  - Myogenesis is a tightly controlled process involving the transcriptional
      activation and repression of thousands of genes. Although many components of the
      transcriptional network regulating the later phases of myogenesis have been
      identified, relatively few studies have described the transcriptional landscape
      during the first 24 h, when myoblasts commit to differentiate. Through dense
      temporal profiling of differentiating C2C12 myoblasts, we identify 193
      transcriptional regulators (TRs) whose expression is significantly altered within
      the first 24 h of myogenesis. A high-content shRNA screen of 77 TRs involving 427
      stable lines identified 42 genes whose knockdown significantly inhibits
      differentiation of C2C12 myoblasts. Of the TRs that were differentially expressed
      within the first 24 h, over half inhibited differentiation when knocked down,
      including known regulators of myogenesis (Myod1, Myog, and Myf5), as well as 19
      TRs not previously associated with this process. Surprisingly, a similar
      proportion (55%) of shRNAs targeting TRs whose expression did not change also
      inhibited C2C12 myogenesis. We further show that a subset of these TRs inhibits
      myogenesis by downregulating expression of known regulatory and structural
      proteins. Our findings clearly illustrate that several TRs critical for C2C12
      myogenesis are not differentially regulated, suggesting that approaches that
      focus functional studies on differentially-expressed transcripts will fail to
      provide a comprehensive view of this complex process.

PMID- 22147265
TI  - Phosphatase and tensin homologue (PTEN) regulates synaptic plasticity
      independently of its effect on neuronal morphology and migration.
AB  - The tumour suppressor PTEN is the central negative regulator of the
      phosphatidylinositol 3-kinase (PI3K) signalling pathway, which mediates diverse
      processes in various tissues. In the nervous system, the PI3K pathway modulates
      proliferation, migration, cellular size, synaptic transmission and plasticity. In
      humans, neurological abnormalities such as autism, seizures and ataxia are
      associated with inherited PTEN mutations. In rodents, Pten loss during early
      development is associated with extensive deficits in neuronal migration and
      substantial hypertrophy of neurons and synaptic densities; however, whether its
      effect on synaptic transmission and plasticity is direct or mediated by
      structural abnormalities remains unknown. Here we analysed neuronal and synaptic
      structures and function in Pten-conditional knockout mice in which the gene was
      deleted from excitatory neurons postnatally. Using two-photon imaging, Golgi
      staining, immunohistochemistry, electron microscopy, and electrophysiological
      tools, we determined that Pten loss does not affect hippocampus development,
      neuronal or synaptic structures, or basal excitatory synaptic transmission.
      However, it does cause deficits in both major forms of synaptic plasticity, long
      term potentiation and long-term depression, of excitatory synaptic transmission.
      These deficits coincided with impaired spatial memory, as measured in water maze
      tasks. Deletion of Pdk1, which encodes a positive downstream regulator of the
      PI3K pathway, rescued Pten-mediated deficits in synaptic plasticity but not in
      spatial memory. These results suggest that PTEN independently modulates
      functional and structural properties of hippocampal neurons and is directly
      involved in mechanisms of synaptic plasticity.

PMID- 22147267
TI  - Expression of genes involved in energy homeostasis in the duodenum and liver of
      Holstein-Friesian and Jersey cows and their F(1) hybrid.
AB  - Differences in feed intake and production efficiency in lactating Holstein
      Friesian (HF), Jersey (JE), and JE * HF (F(1)) dairy cows have been reported. The
      liver-gut axis is important in the regulation of energy homeostasis, appetite
      behaviour, and production efficiency. The objectives of this study were to
      determine: 1) the effect of dairy cow genotype on the expression profiles of
      genes involved in energy homeostasis in duodenal and hepatic tissue, and 2) the
      association between the expression of these genes across both tissues and with
      economically important production efficiency traits. The expression of 27
      candidate genes involved in energy homeostasis, feed intake, and energy storage
      was measured by qPCR. Duodenal expression of the pro-opiomelanocortin (POMC),
      glucagon-like peptide 1 receptor (GLP1R), and insulin-like growth factor 1 (IGF1)
      genes was highest in HF. In contrast, hepatic expression of the leptin receptor
      (LEPR), insulin-like growth factor 1 receptor (IGF1R), protein kinase, AMP
      activated, beta 1 (AMPKB1), and POMC genes was highest in the F(1) cross. In the
      duodenum, positive correlations were observed between mRNA expression of
      anorectic peptides (POMC and GLP1R), whereas a negative correlation was detected
      between orexigenic (ghrelin) and anorectic (peptide YY) gene expression. A
      negative correlation was observed between duodenal POMC gene expression and both
      residual feed intake and milk production efficiency traits, while GLP1R gene
      expression was negatively correlated with milk production efficiency traits. A
      heterotic effect was observed in hepatic expression of AMKPB1, IGF1R, LEPR, POMC
      in the F(1) genotype, possibly mediating improved feed efficiency in cross-bred
      cows. In conclusion, key genes involved in energy homeostasis and appetite
      behaviour are differentially expressed due to cow genotype in a tissue-dependent
      fashion. POMC and GLP1R are potential candidate genes for the identification of
      single nucleotide polymorphisms regulating energetic efficiency in the dairy cow,
      which may be incorporated into future breeding programmes.

PMID- 22147268
TI  - Influence of atrial fibrillation on microRNA expression profiles in left and
      right atria from patients with valvular heart disease.
AB  - Chronic atrial fibrillation (AF) is a complication associated with the dilated
      atria of patients with valvular heart disease and contributes to worsened
      pathology. We examined microRNA (miRNA) expression profiles in right and left
      atrial appendage tissue from valvular heart disease (VHD) patients. Right atrial
      (RA) appendage from patients undergoing coronary artery bypass grafting and left
      atrial (LA) appendage from healthy hearts, not used for transplant, were used as
      controls. There was no detectable effect of chronic AF on miRNA expression in LA
      tissue, but miRNA expression in RA was strongly influenced by AF, with 47 miRNAs
      (15 higher, 32 lower) showing differential expression between the AF and control
      sinus rhythm groups. VHD induced different changes in miRNA expression in LA
      compared with RA. Fifty-three (12 higher, 41 lower) miRNAs were altered by VHD in
      LA, compared with 5 (4 higher, 1 lower) in RA tissue. miRNA profiles also
      differed between VHD-LA and VHD-RA (13 higher, 26 lower). We conclude that VHD
      and AF influence miRNA expression patterns in LA and RA, but these are affected
      differently by disease progression and by the development of AF. These findings
      provide new insights into the progression of VHD.

PMID- 22147270
TI  - A hydrolysis procedure for the analysis of total cocaine residues in wastewater.
AB  - We report a sample pretreatment approach for the analysis of total cocaine
      residues in wastewater that eliminates the need for two key assumptions often
      made in estimating cocaine utilization from measurement of its benzoylecgonine
      metabolite: that benzoylecgonine is neither degraded nor generated during
      transport in a sewer system, and that it is excreted as a constant fraction of
      cocaine ingested. By adding NaOH and incubating samples at 55  degrees C, cocaine
      and its principal metabolites are efficiently hydrolyzed into ecgonine,
      anhydroecgonine, and norecgonine. Ecgonine, estimated to represent between 37%
      and 90% (on a molar basis) of cocaine residues, can be directly determined
      (without preconcentration via solid-phase extraction (SPE)) by reversed-phase
      (RP) or hydrophilic interaction liquid chromatography-tandem mass spectrometry
      (LC/MS/MS). If samples are subjected to SPE, anhydroecgonine can also be
      determined; this metabolite (and its precursors) represents ~7% of urinary
      cocaine residues (based on spot collections from living individuals). Although a
      reference standard for norecgonine is not commercially available, such
      nortropanes are also a minor fraction (up to 2%) of urinary cocaine residues. The
      stability of two human markers (cotinine and creatinine) to the hydrolysis
      procedure was also investigated. Results obtained by applying the hydrolysis
      approach for the analysis of total cocaine in an untreated municipal wastewater
      sample (obtained from Baltimore, MD) were generally in excellent agreement with
      those obtained from split samples analyzed using a more comprehensive solid-phase
      extraction RPLC/MS/MS method as described in our previous work. In particular,
      total tropane-based cocaine residues were found to be hydrolyzed to ecgonine with
      98-99% efficiency.

PMID- 22147271
TI  - Selective accurate-mass-based analysis of 11 oxy-PAHs on atmospheric particulate
      matter by pressurized liquid extraction followed by high-performance liquid
      chromatography and magnetic sector mass spectrometry.
AB  - An innovative analytical method based on high-performance liquid chromatography
      and atmospheric pressure chemical ionization magnetic sector mass spectrometry
      was developed and optimized to determine trace concentrations of 11 compounds
      belonging to the group of the seldom-analyzed oxy-PAHs (phenanthrene-9,10-dione,
      chrysene-5,6-dione, benzo[a]pyrene-4,5-dione, benzo[a]pyrene-1,6-dione,
      benzo[a]pyrene-3,6-dione, benzo[a]pyrene-6,12-dione, 4-oxa-benzo[def]chrysene-5
      one, pyrene-1-carboxaldehyde, benzo[de]anthracene-7-one, benzo[a]anthracene-7,12
      dione, and napthacene-5,12-dione) on airborne particulate matter (PM(10)). The
      mass spectrometer was operated in multiple ion detection mode, allowing for
      selective accurate mass detection (mass resolution of 12,000 full width at half
      maximum) of the oxy-PAHs characteristic ions. Optimization of both the vaporizer
      (450  degrees C) and capillary temperature (350  degrees C) resulted into
      instrumental detection limits in the range between 7 (benzo[a]pyrene-1,6-dione)
      and 926 pg (benzo[a]anthracene-7,12-dione). The advanced pressurized liquid
      extraction (PLE) and the more traditionally used ultrasonic extraction (USE) were
      compared using ethyl acetate as an extraction solvent. For both techniques, high
      recoveries from spiked quartz fiber filters (PLE, 82-110%; USE, 67-97%) were
      obtained. Recoveries obtained from real PM(10) samples were also high (76-107%),
      and no significant matrix effects (ME) on the ionization process (enhancement or
      suppression) were found (ME, 89-123%). Method limits of quantification (S/N = 10)
      were in the range between 2 and 336 pg/m(3). This method was used to analyze real
      PM samples collected at several urban and rural locations in the Antwerp area.
      For the first time, concentrations for Belgium are provided. Concentrations of
      individual oxy-PAHs are in the lower pictograms per cubic meter to 6 ng/m(3)
      range. High concentration differences between individual compounds are found as
      exemplified by the 75th percentile of the phenanthrene-9,10-dione and
      benzo[de]anthracene-7-one concentrations being a factor of 4 to 22 higher
      compared with the other target oxy-PAHs.

PMID- 22147269
TI  - Upregulation of heme oxygenase-1 by acteoside through ERK and PI3 K/Akt pathway
      confer neuroprotection against beta-amyloid-induced neurotoxicity.
AB  - Our previous study has shown that acteoside, an antioxidative phenylethanoid
      glycoside, protect against beta-amyloid (Abeta)-induced cytotoxicity in vitro.
      However, the precise protective mechanisms remains unclear. Heme oxygenase-1 (HO
      1) is a crucial factor in the response to oxidative injury, protecting neurons
      against Abeta-induced injury. In the present study we examined to determine
      whether acteoside upregulates HO-1 expression, and thereby protects PC12 cells
      against Abeta-induced cell death. It was revealed that acteoside is an activator
      of Nrf2 and inducer of HO-1 expression. We showed that acteoside increased HO-1
      expression in vitro and in vivo. Acteoside treatment resulted in nuclear
      translocation of the transcription factor NF-E2-related factor 2 (Nrf2).
      Acteoside activated both ERK and PI3 K/Akt, and treatments with the specific ERK
      inhibitor PD98059, the PI3 K inhibitor LY294002, and the specific Nrf2 siRNA
      suppressed the acteoside-induced HO-1 expression. The HO-1 inhibitor ZnPP,
      PD98059, and LY294002 markedly abolished the neuroprotective effect of acteoside
      against Abeta-induced neurotoxicity. Taken together, these results demonstrate
      that acteoside is an activator of Nrf2 and inducer of HO-1 expression. We also
      showed that acteoside increased HO-1 expression through activation of ERK and PI3
      K/Akt signal pathways in vitro. Upregulation of HO-1 by acteoside may involve in
      the neuroprotection against Abeta-induced neurotoxicity.

PMID- 22147272
TI  - Rapid, simple, and highly sensitive analysis of drugs in biological samples using
      thin-layer chromatography coupled with matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - Rapid and precise identification of toxic substances is necessary for urgent
      diagnosis and treatment of poisoning cases and for establishing the cause of
      death in postmortem examinations. However, identification of compounds in
      biological samples using gas chromatography and liquid chromatography coupled
      with mass spectrometry entails time-consuming and labor-intensive sample
      preparations. In this study, we examined a simple preparation and highly
      sensitive analysis of drugs in biological samples such as urine, plasma, and
      organs using thin-layer chromatography coupled with matrix-assisted laser
      desorption/ionization mass spectrometry (TLC/MALDI/MS). When the urine containing
      3,4-methylenedioxymethamphetamine (MDMA) without sample dilution was spotted on a
      thin-layer chromatography (TLC) plate and was analyzed by TLC/MALDI/MS, the
      detection limit of the MDMA spot was 0.05 ng/spot. The value was the same as that
      in aqueous solution spotted on a stainless steel plate. All the 11 psychotropic
      compounds tested (MDMA, 4-hydroxy-3-methoxymethamphetamine, 3,4
      methylenedioxyamphetamine, methamphetamine, p-hydroxymethamphetamine,
      amphetamine, ketamine, caffeine, chlorpromazine, triazolam, and morphine) on a
      TLC plate were detected at levels of 0.05-5 ng, and the type (layer thickness and
      fluorescence) of TLC plate did not affect detection sensitivity. In addition,
      when rat liver homogenate obtained after MDMA administration (10 mg/kg) was
      spotted on a TLC plate, MDMA and its main metabolites were identified using
      TLC/MALDI/MS, and the spots on a TLC plate were visualized by MALDI/imaging MS.
      The total analytical time from spotting of intact biological samples to the
      output of analytical results was within 30 min. TLC/MALDI/MS enabled rapid,
      simple, and highly sensitive analysis of drugs from intact biological samples and
      crude extracts. Accordingly, this method could be applied to rapid drug screening
      and precise identification of toxic substances in poisoning cases and postmortem
      examinations.

PMID- 22147273
TI  - Species-specific identification of ruminant components contaminating industrial
      crude porcine heparin using real-time fluorescent qualitative and quantitative
      PCR.
AB  - Ever since the emergence of bovine spongiform encephalopathy, the source of
      pharmaceutical heparin has been restricted to porcine intestinal mucosa. In this
      project, two real-time fluorescent PCR methods were developed to assist with
      quality control analysis. The first is a qualitative method which relies on SYBR
      Green I chemistry to confirm the porcine origin of industrial crude porcine
      heparin (ICPH), identify any ruminant contaminants, and generally control purity.
      The second is based on TaqMan chemistry and is able to quantitatively identify
      porcine, bovine, caprine, and ovine components and contaminants in ICPH. By
      targeting mitochondrial DNA, both PCR systems showed a detection limit of 1 pg
      DNA and amplification efficiencies ranging between 96% and 102%. Moreover,
      quantitative PCR showed a detection limit of 0.02 ppm in samples comprising
      porcine, bovine, caprine, and ovine DNA. The results of qualitative PCR over 27
      ICPH samples showed that all samples were porcine in origin and that 17 had
      ruminant contaminants. The results of quantitative PCR further showed that out of
      all 17 samples with ruminant contaminants, seven samples had bovine, ovine, and
      caprine contaminants, two samples had bovine and ovine contaminants, and eight
      samples had only ovine contaminants. In conclusion, the qualitative PCR system
      was found to be a relatively inexpensive, rapid, and flexible method of
      identifying the porcine origin of and ruminant contaminants in ICPH, while the
      quantitative PCR was found suitable to accurately analyze the components and
      contaminants in detail. Both methods are suitable for routine control assays for
      the evaluation of ICPH purity and origins of contaminants.

PMID- 22147274
TI  - Recurrent bacterial meningitis by three different pathogens in an isolated
      asplenic child.
AB  - Isolated congenital asplenia (ICA) is a rare condition at risk for overwhelming
      infection. When complicated by invasive infection, the mortality remains high, at
      greater than 60%. We describe a girl with ICA who developed recurrent meningitis
      by three different pathogens. The first, meningitis by Escherichia coli, occurred
      4 days after premature birth. The other two pathogens were serotype 6B
      Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), at 18 and 25
      months of age, respectively. The patient was successfully treated with prompt
      antimicrobial therapy in all episodes. Serum anti-polyribosylribitol phosphate
      (PRP) and anti-6B-type pneumococcal antibodies were below the levels for
      protective activity after natural infections. Although anti-PRP antibody was
      significantly increased after Hib vaccination, two (6B and 19F) of seven serotype
      specific pneumococcal antibodies were not elevated to protective levels after the
      second 7-valent pneumococcal conjugate vaccine (PCV7). We, therefore, added a
      third PCV7. To our knowledge, this is the first neonatal ICA patient with
      invasive infection and the first case of bacterial meningitis occurring three
      times. Our findings indicate that monitoring of immune responses after natural
      infections and vaccinations, and reevaluations of vaccine schedule, are important
      for ICA patients to prevent subsequent invasive infections.

PMID- 22147275
TI  - Virulence of Sporothrix luriei in a murine model of disseminated infection.
AB  - Sporothrix luriei is a rare fungus causing sporotrichosis in humans. The
      virulence of this fungus was evaluated in a murine model of disseminated
      infection. Mice were challenged intravenously with two different inocula (2 *
      10(5) and 2 * 10(7) CFU/animals) but only the highest one was able to kill the
      animals. Infected mice died between days 12 and 16, liver and spleen being the
      most affected organs. In the infected tissues, a massive infiltration of fungal
      cells and phagocytes were observed, but not the typical "eyeglass" cells
      described in infected human tissue.

PMID- 22147276
TI  - Intracranial hypertension and the importance of cerebral venous drainage
      variability: a case report of headache as the initial clinical presentation of an
      intraspinal paraganglioma.

PMID- 22147277
TI  - Diagnostic discography: what is the clinical utility?
AB  - The diagnosis and treatment of discogenic back pain is challenging. Provocation
      discography, an invasive spinal procedure, has been suggested as a diagnostic
      test for internal disc disruption to provide information on disc morphology and
      reproduction of symptoms. Current applications consist of the evaluation of
      persistent spinal pain in individuals, including postoperative patients, as well
      as providing a guide for patient selection for spinal fusion surgery and
      minimally invasive interventional pain procedures. While the validity of
      discography has been questioned by multiple scientific studies, technical
      refinements have addressed many of the initial limitations. An updated review on
      the safety and utility of discography will be provided, covering key areas of
      debate including false-positive rates, technical parameters, clinical utility,
      and risk of discography procedural-related intervertebral disc damage.

PMID- 22147278
TI  - The effect of oral glucose tolerance test on serum osteocalcin and bone turnover
      markers in young adults.
AB  - Osteocalcin (OC) is an osteoblast-derived protein implicated in the regulation of
      glucose tolerance and energy metabolism. This endocrine function has been
      suggested to be exerted via its undercarboxylated form, which has been shown to
      induce expression of adiponectin, insulin, and islet cell proliferation in mice.
      Furthermore, insulin has recently been shown to regulate the biological activity
      of OC in bone. Our aim was to explore the association between glucose and bone
      metabolism by evaluating the effect of a standard 75 g oral glucose tolerance
      test (OGTT) on serum OC, carboxylated OC (cOC) and bone-turnover markers (BTMs) C
      terminal telopeptide (betaCTX-I) and N terminal propeptide (PINP) of type I
      collagen and tartrate-resistant acid phosphatase 5b (TRACP5b). Serum samples
      collected at 0 and at 120 min were analyzed in a cohort of normoglycemic young
      adults (n = 23, mean age 23.6 years). During OGTT a significant decrease was
      observed in all BTMs (P < 0.001 for all variables). The median decreases from 0
      to 120 min for OC, cOC, betaCTX-I, PINP, and TRACP5b were -32.1% (-37.9 to 
      19.6), -34.4% (-39.8 to -22.2), -61.4% (-68.5 to -53.0), -26.8% (-33.2 to -19.2),
      and -44.5% (-48.3 to -40.2), respectively. A strong association between the
      changes in OC and cOC was observed (r = 0.83, P < 0.001). The decrease in PINP
      was associated with changes in OC, whereas the changes in betaCTX-I and TRACP5b
      were not associated with decreases in OC or cOC. The observed OGTT-induced
      changes in bone-derived proteins were partially independent of each other and
      potentially mediated by different mechanisms.

PMID- 22147279
TI  - Biobank governance: heterogeneous modes of ordering and democratization.
AB  - The great interest in biobanks, the related, substantial investments, and the
      expectations connected with them raises the question of how to explain the
      relative successes and failures of contemporary biobank projects. In this article
      we will present and discuss areas that need ongoing attention by many
      stakeholders in order stabilize and utilize biobanks and biobank networks in the
      future. Our aim is to present and utilize an analytical model for comparing
      structures of biobank governance. The governance model we deduce from empirical
      case studies is not a well-ordered, almost bureaucratic type of government. The
      patchwork character and the interrelatedness of heterogeneous activities that
      constitute biobank governance in its multiple dimensions will be highlighted.
      Biobank governance should therefore be understood as strategy for patterning a
      network of interaction that unfolds within and across a number of different
      fields including a variety of activities that go beyond regulatory activities:
      the scientific/technological field, the medical/health field, the industrial
      economic field, the legal-ethical, and the sociopolitical field. Our account
      emphasizes that biobanks are not technical visions that operate vis-a-vis an
      external society. The article discusses attempts to develop participatory
      governance structures. It concludes that facilitating and managing the
      integration of a network of more or less interrelated actors, in many
      nonhierarchic ways, should not be equated with democratization per se, but can
      nevertheless be regarded as an important step towards a more pluralistic and
      inclusive style of policy making.

PMID- 22147280
TI  - Children and adolescents with chronic constipation: how many seek healthcare and
      what determines it?
AB  - This island-wide cross-sectional survey was conducted to assess the healthcare
      consultations in Sri Lankan children with constipation. Children aged 10-16 years
      were randomly selected from five randomly selected schools in three randomly
      selected provinces of Sri Lanka. Data were collected using a pre-tested
      questionnaire based on Rome III criteria. Of the 2770 questionnaires distributed,
      2694 (97.3%) properly filled questionnaires were included in the analysis. From
      416 (15.4%) children with chronic constipation, only 16 (3.8%) had sought medical
      advice during the previous 12 months. Younger children and those with a similar
      family history were more likely to seek healthcare. The majority of children with
      symptoms indicating severe constipation such as painful defecation, large volume
      stool, faecal incontinence and blood stained stools had not sought medical help
      for their symptoms. Parents should pay more attention to bowel habits of their
      children to identify and treat constipation early to prevent complications.

PMID- 22147281
TI  - Impact of community-based behaviour-change management on perceived neonatal
      morbidity: a cluster-randomized controlled trial in Shivgarh, Uttar Pradesh,
      India.
AB  - In the context of high neonatal mortality rate (NMR) in developing country
      settings, a promising strategy for enhancing newborn health is promotion of
      preventive newborn care practices. We measured the effect of a behaviour-change
      intervention on perceived neonatal illnesses in rural Uttar Pradesh, India. The
      study was nested in a cluster-randomized controlled trial of the impact of a
      package of essential newborn care on NMR. We prospectively enrolled 802 mothers
      and administered a questionnaire on perceived neonatal morbidities. Regression
      analysis showed that newborns in the intervention clusters had significantly
      lower risk of perceived diarrhoea [adjusted relative risk (aRR) 0.67, 95%
      confidence interval (CI) 0.49-0.90] and skin-related complications [aRR 0.67, 95%
      CI 0.45-1.00] compared to newborns in the comparison area. Assuming incidence of
      perceived illnesses is a proxy for actual morbidity rates, we conclude that
      promotion of preventive care practices through behaviour-change interventions was
      effective in reducing neonatal morbidities.

PMID- 22147282
TI  - The effect of renal administration of a selective cyclooxygenase-2 inhibitor or
      stable prostaglandin I2 analog on the progression of sclerotic glomerulonephritis
      in rats.
AB  - BACKGROUND AND METHODS: There is increasing evidence that a change in glomerular
      hemodynamics may promote the development of glomerulosclerosis. In this study, we
      focused on the pharmacological effects of 2 contrasting agents, etodolac, a
      preferential cyclooxygenase-2 inhibitor, and beraprost sodium (BPS), a
      prostaglandin I(2) analog, delivered renally, on the disease course of
      progressive anti-Thy-1 (ATS) glomerulonephritis. RESULTS: Intravital microscopic
      analysis showed that the diameters of glomerular capillaries and glomerular blood
      flow in unilaterally nephrectomized (Nx) rats treated locally with BPS were
      significantly increased, as compared to those of Nx rats treated locally with
      normal saline (NS) or etodolac. We then examined the effects of BPS and etodolac
      on the course of progressive glomerulosclerosis. Mesangial cell proliferation,
      adhesion of glomerular capillary tufts and crescent formation in the BPS-treated
      group appeared to be more severe compared to the ATS + NS and the ATS + etodolac
      groups. Scoring of mesangial proliferation and glomerulosclerosis revealed that
      local BPS treatment significantly worsened glomerular pathology. At day 28, there
      were significant differences in blood flow between the ATS + etodolac group and
      both the ATS + NS and ATS + BPS groups, indicating that local treatment with
      etodolac enhanced the recovery of glomerular circulation. CONCLUSION: This study
      provides hemodynamic-based evidence showing that disturbance of intraglomerular
      microcirculation is a critical marker for progressive glomerulonephritis.

PMID- 22147283
TI  - Sesaminol glucosides protect beta-amyloid induced apoptotic cell death by
      regulating redox system in SK-N-SH cells.
AB  - We have investigated the neuroprotective effect of sesaminol glucosides (SG) in
      SK-N-SH cells. SG prevented apoptotic cell death induced by Abeta25-35. In
      parallel, SK-N-SH cells exposed to Abeta25-35 underwent oxidative stress as shown
      by the elevated level of intracellular ROS, lipid peroxidation, and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) formation, which were effectively suppressed by SG
      treatment. Furthermore, SG reversed the activities of catalase and glutathione
      peroxidase, and restored intracellular GSH levels in Abeta25-35 challenged SK-N
      SH cells. In addition, SG inhibited not only Abeta25-35-induced apoptotic
      features including cleavage of poly(ADP-ribose) polymerase, activation of caspase
      3, and activation of caspase-9, but also elevated Bax/Bcl-2 ratio in SK-N-SH
      cells treated with Abeta25-35. It was also observed that Abeta25-35 stimulated
      the phosphorylation of mitogen-activated protein kinases (MAPKs), including
      extracellular protein regulated protein kinase (ERK), c-Jun N-terminal kinase
      (JNK), and p38 MAP kinase. SG inhibited phosphorylation of the JNK, ERK and p38
      MAP kinase. These results suggest that SG has a protective effect against Abeta25
      35-induced neuronal apoptosis, possibly through scavenging oxidative stress and
      regulating MAPKs signaling pathways.

PMID- 22147284
TI  - Depolarization-induced release of amino acids from the vestibular nuclear
      complex.
AB  - There is evidence from immunohistochemistry, quantitative microchemistry, and
      pharmacology for several amino acids as neurotransmitters in the vestibular
      nuclear complex (VNC), including glutamate, gamma-aminobutyrate (GABA), and
      glycine. However, evidence from measurements of release has been limited. The
      purpose of this study was to measure depolarization-stimulated calcium-dependent
      release of amino acids from the VNC in brain slices. Coronal slices containing
      predominantly the VNC were prepared from rats and perfused with artificial
      cerebrospinal fluid (ACSF) in an interface chamber. Fluid was collected from the
      chamber just downstream from the VNC using a microsiphon. Depolarization was
      induced by 50 mM potassium in either control calcium and magnesium concentrations
      or reduced calcium and elevated magnesium. Amino acid concentrations in effluent
      fluid were measured by high performance liquid chromatography. Glutamate release
      increased fivefold during depolarization in control calcium concentration and
      twofold in low calcium/high magnesium. These same ratios were 6 and 1.5 for GABA,
      2 and 1.3 for glycine, and 2 and 1.5 for aspartate. Differences between release
      in control and low calcium/high magnesium ACSF were statistically significant for
      glutamate, GABA, and glycine. Glutamine release decreased during and after
      depolarization, and taurine release slowly increased. No evidence for calcium
      dependent release was found for serine, glutamine, alanine, threonine, arginine,
      taurine, or tyrosine. Our results support glutamate and GABA as major
      neurotransmitters in the VNC. They also support glycine as a neurotransmitter and
      some function for taurine.

PMID- 22147285
TI  - Compressive force applied to a manikin's head during mask ventilation.
AB  - OBJECTIVE: To investigate the compressive force applied to the head during mask
      ventilation and determine whether this force increases in response to an attempt
      to correct the mask leak. METHODS: The authors asked 24 participants
      (consultants, fellows and nurses) to administer positive pressure ventilation to
      a modified leak-free, term newborn manikin using a self-inflating bag (SIB) and a
      Neopuff T-piece device. Recordings were made before and after the participants
      were informed about their percentage of mask leak and asked to correct this.
      Airway pressure and flow were measured using a Florian monitor, and the force
      applied to the head was measured using a concealed custom-made load cell weighing
      scale. RESULTS: There were no differences in the mean (SD) force applied to the
      head between devices used and before or after the attempt to correct the mask
      leak (SIB before 2215 (892) and after 2195 (989) g; Neopuff before 1949 (957) and
      after 2028 (909) g). There was a large variation in force with both devices
      before and after the attempt (coefficient of variation: SIB before 40% and after
      45%; Neopuff before 50% and after 45%). There was no correlation between mask
      leak and the difference in force used before and after the attempt to correct the
      mask leak using both devices. CONCLUSION: During mask ventilation of a manikin,
      the authors observed that large forces were exerted on the head with either an
      SIB or a Neopuff, but these forces did not increase during the attempt to
      minimise the mask leak.

PMID- 22147286
TI  - Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a
      randomised controlled trial in extremely low birthweight infants.
AB  - OBJECTIVE: To compare the efficacy and safety of oral versus intravenous
      ibuprofen for the pharmacological closure of patent ductus arteriosus (PDA) in
      less mature preterm infants. DESIGN: Prospective, randomised controlled study.
      SETTING: Tertiary neonatal intensive care unit. PATIENTS AND INTERVENTIONS: The
      study enrolled 80 preterm infants with gestational age <=28 weeks, birth weight
      <1000 g, postnatal age 48 to 96 h, and had echocardiographically confirmed
      significant PDA. Seventy extremely low birthweight (ELBW) preterm infants
      received either intravenous or oral ibuprofen randomly as an initial dose of 10
      mg/kg, followed by 5 mg/kg at 24 and 48 h. MAIN OUTCOME MEASURES: The success
      rate and the safety of the drugs in ELBW preterm infants were the major outcomes.
      RESULTS: PDA closure rate was significantly higher with oral ibuprofen (83.3% vs
      61.7%) after the first course of the treatment (p=0.04). Although the primary
      closure rate was marginally higher in the oral ibuprofen group, the need for a
      second course of ibuprofen during the whole hospitalisation was similar between
      groups: 11 of 36 in oral versus 15 of 34 in intravenous groups (p=0.24) because
      of a higher reopening rate in the oral group. In addition to no increase in side
      effects with oral ibuprofen use, the need for postnatal steroid use for chronic
      lung disease was significantly lower in oral ibuprofen group (p=0.001).
      CONCLUSIONS: Oral ibuprofen is as effective as intravenous ibuprofen for PDA
      closure even in ELBW infants.

PMID- 22147287
TI  - Metoclopramide or domperidone for increasing maternal breast milk output: a
      randomised controlled trial.
AB  - OBJECTIVE: To compare the effects of metoclopramide and domperidone on the breast
      milk output of mothers with infants in neonatal intensive care. DESIGN: Double
      blind randomised controlled trial. SETTING: Tertiary level neonatal intensive
      care unit (NICU). SAMPLE: Eighty mothers expressing breast milk for their infants
      (mean gestational age 28 weeks) based in NICU and the amounts expressed fell
      short of the prescribed target. INTERVENTION: Mothers were randomised to receive
      domperidone or metoclopramide for 10 days (10 mg three times a day). OUTCOME
      MEASURES: Total milk volume daily for up to 10 days before the medication, 10
      days during the trial and up to 10 days after medication. Adverse side effects
      were also recorded. RESULTS: Mothers produced more milk in the domperidone group
      and achieved a mean of 96.3% increase in milk volume (mean increase/pretrial
      volume) compared with a 93.7% increase for metoclopramide. After adjusting for
      the amount of milk produced prior to medication, the mean amount of milk produced
      while taking medication for those on domperidone was 31.0 ml/24 h (95% CI -5.67
      to 67.6) greater than the mean for those on metoclopramide. Seven mothers taking
      metoclopramide reported side effects and three taking domperidone; a further
      eight women (of 29) who had a follow-on prescription for metoclopramide also
      reported side effects. CONCLUSIONS: Oral domperidone and metoclopramide increased
      the volume of milk produced by mothers who are expressing to feed their babies in
      NICU. There were small differences in milk output between the two medications and
      in the incidence of side effects, but the differences were non-significant.

PMID- 22147288
TI  - L1-norm-based common spatial patterns.
AB  - Common spatial patterns (CSP) is a commonly used method of spatial filtering for
      multichannel electroencephalogram (EEG) signals. The formulation of the CSP
      criterion is based on variance using L2-norm, which implies that CSP is sensitive
      to outliers. In this paper, we propose a robust version of CSP, called CSP-L1, by
      maximizing the ratio of filtered dispersion of one class to the other class, both
      of which are formulated by using L1-norm rather than L2-norm. The spatial filters
      of CSP-L1 are obtained by introducing an iterative algorithm, which is easy to
      implement and is theoretically justified. CSP-L1 is robust to outliers.
      Experiment results on a toy example and datasets of BCI competitions demonstrate
      the efficacy of the proposed method.

PMID- 22147289
TI  - Improving myoelectric pattern recognition robustness to electrode shift by
      changing interelectrode distance and electrode configuration.
AB  - Pattern recognition of myoelectric signals for prosthesis control has been
      extensively studied in research settings and is close to clinical implementation.
      These systems are capable of intuitively controlling the next generation of
      dexterous prosthetic hands. However, pattern recognition systems perform poorly
      in the presence of electrode shift, defined as movement of surface electrodes
      with respect to the underlying muscles. This paper focused on investigating the
      optimal interelectrode distance, channel configuration, and electromyography
      feature sets for myoelectric pattern recognition in the presence of electrode
      shift. Increasing interelectrode distance from 2 to 4 cm improved pattern
      recognition system performance in terms of classification error and
      controllability (p < 0.01). Additionally, for a constant number of channels, an
      electrode configuration that included electrodes oriented both longitudinally and
      perpendicularly with respect to muscle fibers improved robustness in the presence
      of electrode shift (p < 0.05). We investigated the effect of the number of
      recording channels with and without electrode shift and found that four to six
      channels were sufficient for pattern recognition control. Finally, we
      investigated different feature sets for pattern recognition control using a
      linear discriminant analysis classifier and found that an autoregressive set
      significantly (p < 0.01) reduced sensitivity to electrode shift compared to a
      traditional time-domain feature set.

PMID- 22147291
TI  - Recent developments and applications of EMMA in enzymatic and derivatization
      reactions.
AB  - This review provides systematic coverage of examples in the field of in-capillary
      electrophorecially mediated microanalysis (EMMA). The recent developments and
      applications in the time period up to mid 2011 have been described, as well as
      relevant older papers. The basic principles and modes of in-capillary assays have
      been demonstrated. An overview is also given of the various injection, separation
      and detection modes implemented in combination with EMMA. The review is presented
      in two parts mainly dealing with (i) enzymatic and (ii) derivatization or
      chemical reactions. Finally, the future trends of CE in performing and monitoring
      reactions have been drawn.

PMID- 22147290
TI  - The Arabidopsis tail-anchored protein PEROXISOMAL AND MITOCHONDRIAL DIVISION
      FACTOR1 is involved in the morphogenesis and proliferation of peroxisomes and
      mitochondria.
AB  - Peroxisomes and mitochondria are multifunctional eukaryotic organelles that are
      not only interconnected metabolically but also share proteins in division. Two
      evolutionarily conserved division factors, dynamin-related protein (DRP) and its
      organelle anchor FISSION1 (FIS1), mediate the fission of both peroxisomes and
      mitochondria. Here, we identified and characterized a plant-specific protein
      shared by these two types of organelles. The Arabidopsis thaliana PEROXISOMAL and
      MITOCHONDRIAL DIVISION FACTOR1 (PMD1) is a coiled-coil protein tethered to the
      membranes of peroxisomes and mitochondria by its C terminus. Null mutants of PMD1
      contain enlarged peroxisomes and elongated mitochondria, and plants
      overexpressing PMD1 have an increased number of these organelles that are smaller
      in size and often aggregated. PMD1 lacks physical interaction with the known
      division proteins DRP3 and FIS1; it is also not required for DRP3's organelle
      targeting. Affinity purifications pulled down PMD1's homolog, PMD2, which
      exclusively targets to mitochondria and plays a specific role in mitochondrial
      morphogenesis. PMD1 and PMD2 can form homo- and heterocomplexes. Organelle
      targeting signals reside in the C termini of these proteins. Our results suggest
      that PMD1 facilitates peroxisomal and mitochondrial proliferation in a FIS1/DRP3
      independent manner and that the homologous proteins PMD1 and PMD2 perform
      nonredundant functions in organelle morphogenesis.

PMID- 22147292
TI  - Lifetime romantic attachment style and social adaptation in late-onset
      depression.
AB  - BACKGROUND: Measuring social adjustment (including attachment style and current
      social adaptation) in late-life depression may support planning secondary
      prevention, rehabilitation, and treatment. Insecure attachment style is a risk
      factor for developing new depression, and social adjustment may constitute a
      problem after symptoms abatement. Few studies have examined attachment style and
      social adjustment in late-onset depression. DESIGN: Subjects 50 years of age and
      older with early-onset (n = 35), late-onset DSM-IV unipolar depression (n = 38),
      and never-depressed volunteers (n = 47) were assessed with a widely used measure
      of attachment style (the Experiences in Close Relationship Scale). Social
      adjustment was measured using the Social Adjustment Scale. RESULTS: Both early
      onset and late-onset patients with depression showed greater insecure attachment
      and poorer social adaptation compared with never-depressed volunteers. No
      difference was found between early-onset and late-onset patients with depression
      on attachment style or social adjustment. There were no significant differences
      between late-life depression in remission or current on attachment or social
      adaptation. CONCLUSION: Insecure attachment style may be a risk factor for late
      life depression irrespective of the age of onset. Social maladaptation may
      persist among individuals with late-life depression in remission.

PMID- 22147293
TI  - Outer membrane targeting of Pseudomonas aeruginosa proteins shows variable
      dependence on the components of Bam and Lol machineries.
AB  - In Gram-negative bacteria, the Lol and Bam machineries direct the targeting of
      lipidated and nonlipidated proteins, respectively, to the outer membrane (OM).
      Using Pseudomonas aeruginosa strains with depleted levels of specific Bam and Lol
      proteins, we demonstrated a variable dependence of different OM proteins on these
      targeting pathways. Reduction in the level of BamA significantly affected the
      ability of the beta-barrel membrane protein OprF to localize to the OM, while the
      targeting of three secretins that are functionally related OM proteins was less
      affected (PilQ and PscC) or not at all affected (XcpQ). Depletion of LolB
      affected all lipoproteins examined and had a variable effect on the nonlipidated
      proteins. While the levels of OprF, PilQ, and PscC were significantly reduced by
      LolB depletion, XcpQ was unaffected and was correctly localized to the OM. These
      results suggest that certain beta-barrel proteins such as OprF primarily utilize
      the complete Bam machinery. The Lol machinery participates in the OM targeting of
      secretins to variable degrees, likely through its involvement in the assembly of
      lipidated Bam components. XcpQ, but not PilQ or PscC, was shown to assemble
      spontaneously into liposomes as multimers. This work raises the possibility that
      there is a gradient of utilization of Bam and Lol insertion and targeting
      machineries. Structural features of individual proteins, including their beta
      barrel content, may determine the propensity of these proteins for folding (or
      misfolding) during periplasmic transit and OM insertion, thereby influencing the
      extent of utilization of the Bam targeting machinery, respectively. IMPORTANCE:
      Targeting of lipidated and nonlipidated proteins to the outer membrane (OM)
      compartment in Gram-negative bacteria involves the transfer across the periplasm
      utilizing the Lol and Bam machineries, respectively. We show that depletion of
      Bam and Lol components in Pseudomonas aeruginosa does not lead to a general OM
      protein translocation defect, but the severity (and therefore, Lol and Bam
      dependence), varies with individual proteins. XcpQ, the secretin component of the
      type II secretion apparatus, is translocated into the OM without the assistance
      of Bam or Lol machineries. The hypothesis that XcpQ, after secretion across the
      cytoplasmic membrane, does not utilize the OM targeting machineries was supported
      by demonstrating that in vitro-synthesized XcpQ (but not the other P. aeruginosa
      secretins) can spontaneously incorporate into lipid vesicles. Therefore, the
      requirement for ancillary factors appears to be, in certain instances, dictated
      by the intrinsic properties of individual OM proteins, conceivably reflecting
      their propensities to misfold during periplasmic transit.

PMID- 22147295
TI  - Pd-catalyzed multiple C-H functionalization to construct biologically active
      compounds from aryl aldoxime ethers with arenes.

PMID- 22147296
TI  - Fast conventional Fmoc solid-phase peptide synthesis: a comparative study of
      different activators.
AB  - The ability to speed up conventional Fmoc solid-phase peptide synthesis (SPPS)
      has many advantages including increased productivity. One way to speed up
      conventional Fmoc SPPS is the choice of activator. Recently, several new
      activators have been introduced into the market, and they were evaluated along
      with some older activators for their ability to synthesize a range of peptides
      with shorter and longer reaction times. It was found that HDMC, PyClock, COMU,
      HCTU, and HATU worked well at shorter reaction times (2 * 1 min), but PyOxim and
      TFFH only worked well at longer reaction times. The performance of PyBOP at
      shorter reaction times was poor only for more difficult sequences. These results
      are important for selecting an appropriate activator for fast SPPS applications.

PMID- 22147298
TI  - The relationship of lower limb muscle strength and knee joint hyperextension
      during the stance phase of gait in hemiparetic stroke patients.
AB  - BACKGROUND AND PURPOSE: Despite the finding that 40% to 60% of stroke patients
      suffer from knee joint hyperextension during gait, there is a lack of agreement
      of the possible causes of this problem. The aim of this study was to determine
      whether there is a relationship between lower limb muscle weakness and knee joint
      hyperextension in hemiparetic stroke patients. METHODS: This is a cross-sectional
      observational comparison study. Twenty patients (mean age 66 years) who had
      suffered a single hemiparetic stroke and were ambulant with no major lower limb
      joint pathology participated. Muscle strength of the hip extensors, hip flexors,
      hip abductors, knee extensors, knee flexors, ankle plantarflexors and ankle
      dorsiflexors of both limbs was measured using a hand-held dynamometer.
      Computerized and visual gait analysis identified subjects with and without knee
      hyperextension in loading response and midstance. Subjects were categorized as
      having weakness of a particular muscle group if the difference in strength
      between the paretic and non-paretic muscle was greater than 50%. The Pearson's
      chi-squared test was used to evaluate the association between weakness and knee
      hyperextension. RESULTS: A strong relationship was found between ankle
      plantarflexor weakness and knee hyperextension during midstance (p = 0.044). No
      relationship was found between lower limb muscle weakness and knee hyperextension
      during loading response (p > 0.05). No relationship was found between any other
      lower limb muscle groups and knee hyperextension in midstance (p > 0.05).
      CONCLUSIONS: Weak ankle plantarflexors, in particular gastrocnemius, may have an
      important role in the presence of knee hyperextension. The results of this study
      did not support a role for weak hamstrings or quadriceps in knee hyperextension
      during gait. Further research is needed to clarify the role of gastrocnemius
      during the stance phase and to determine if strengthening weak gastrocnemius
      reduces knee hyperextension.

PMID- 22147299
TI  - Data-based robust multiobjective optimization of interconnected processes: energy
      efficiency case study in papermaking.
AB  - Reducing energy consumption is a major challenge for "energy-intensive"
      industries such as papermaking. A commercially viable energy saving solution is
      to employ data-based optimization techniques to obtain a set of "optimized"
      operational settings that satisfy certain performance indices. The difficulties
      of this are: 1) the problems of this type are inherently multicriteria in the
      sense that improving one performance index might result in compromising the other
      important measures; 2) practical systems often exhibit unknown complex dynamics
      and several interconnections which make the modeling task difficult; and 3) as
      the models are acquired from the existing historical data, they are valid only
      locally and extrapolations incorporate risk of increasing process variability. To
      overcome these difficulties, this paper presents a new decision support system
      for robust multiobjective optimization of interconnected processes. The plant is
      first divided into serially connected units to model the process, product
      quality, energy consumption, and corresponding uncertainty measures. Then
      multiobjective gradient descent algorithm is used to solve the problem in line
      with user's preference information. Finally, the optimization results are
      visualized for analysis and decision making. In practice, if further iterations
      of the optimization algorithm are considered, validity of the local models must
      be checked prior to proceeding to further iterations. The method is implemented
      by a MATLAB-based interactive tool DataExplorer supporting a range of data
      analysis, modeling, and multiobjective optimization techniques. The proposed
      approach was tested in two U.K.-based commercial paper mills where the aim was
      reducing steam consumption and increasing productivity while maintaining the
      product quality by optimization of vacuum pressures in forming and press
      sections. The experimental results demonstrate the effectiveness of the method.

PMID- 22147300
TI  - Data-core-based fuzzy min-max neural network for pattern classification.
AB  - A fuzzy min-max neural network based on data core (DCFMN) is proposed for pattern
      classification. A new membership function for classifying the neuron of DCFMN is
      defined in which the noise, the geometric center of the hyperbox, and the data
      core are considered. Instead of using the contraction process of the FMNN
      described by Simpson, a kind of overlapped neuron with new membership function
      based on the data core is proposed and added to neural network to represent the
      overlapping area of hyperboxes belonging to different classes. Furthermore, some
      algorithms of online learning and classification are presented according to the
      structure of DCFMN. DCFMN has strong robustness and high accuracy in
      classification taking onto account the effect of data core and noise. The
      performance of DCFMN is checked by some benchmark datasets and compared with some
      traditional fuzzy neural networks, such as the fuzzy min-max neural network
      (FMNN), the general FMNN, and the FMNN with compensatory neuron. Finally the
      pattern classification of a pipeline is evaluated using DCFMN and other
      classifiers. All the results indicate that the performance of DCFMN is excellent.

PMID- 22147301
TI  - Data-based identification and control of nonlinear systems via piecewise affine
      approximation.
AB  - The piecewise affine (PWA) model represents an attractive model structure for
      approximating nonlinear systems. In this paper, a procedure for obtaining the PWA
      autoregressive exogenous (ARX) (autoregressive systems with exogenous inputs)
      models of nonlinear systems is proposed. Two key parameters defining a PWARX
      model, namely, the parameters of locally affine subsystems and the partition of
      the regressor space, are estimated, the former through a least-squares-based
      identification method using multiple models, and the latter using standard
      procedures such as neural network classifier or support vector machine
      classifier. Having obtained the PWARX model of the nonlinear system, a controller
      is then derived to control the system for reference tracking. Both simulation and
      experimental studies show that the proposed algorithm can indeed provide accurate
      PWA approximation of nonlinear systems, and the designed controller provides good
      tracking performance.

PMID- 22147302
TI  - Data-driven model-free adaptive control for a class of MIMO nonlinear discrete
      time systems.
AB  - In this paper, a data-driven model-free adaptive control (MFAC) approach is
      proposed based on a new dynamic linearization technique (DLT) with a novel
      concept called pseudo-partial derivative for a class of general multiple-input
      and multiple-output nonlinear discrete-time systems. The DLT includes compact
      form dynamic linearization, partial form dynamic linearization, and full form
      dynamic linearization. The main feature of the approach is that the controller
      design depends only on the measured input/output data of the controlled plant.
      Analysis and extensive simulations have shown that MFAC guarantees the bounded
      input bounded-output stability and the tracking error convergence.

PMID- 22147303
TI  - Letter of apology.

PMID- 22147304
TI  - [Access to intermittent preventive treatment (IPt) in a situation of abolition of
      user's fee: role of economic welfare].
AB  - In Senegal, the free distribution of sulfadoxine pyrimethamine during antenatal
      care is recommended to remove the disparity in the context of intermittent
      preventive treatment against malaria. The objective of this study was thus to
      identify factors influencing access to treatment in a situation of abolition of
      user fees. It was a cross-sectional and analytical study. It covered a sample of
      1906 women aged 15-49 years randomly selected during the national survey on
      malaria in Senegal. Data were collected during a personal interview. The economic
      well-being was measured from the characteristics of housing and durable goods.
      The multivariate analysis was performed using logistic regression. The average
      age was 27.94 +/- 5.34, 64.27% resided in rural area and 71.8% had received no
      schooling. Among the surveyed women, 23% were in the poorest quintile, while
      16.3% were in the richest. Intermittent preventive treatment was performed in
      49.3%. IPt were made more in urban areas (OR 1.45 95% [1.17 to 1.72]). It
      increased with the level of education with an OR of 1.5 and 1.68 in primary and
      secondary. The completion of the IPt increased with economic welfare. The OR
      ranged from 1.44 to 2.95 in the second quintile to the richest. Free medication
      does not necessarily benefit poor people. Other accompanying measures must be
      developed to facilitate the distribution of drugs particularly at community level
      with the involvement of people.

PMID- 22147305
TI  - Practical detection of spammers and content promoters in online video sharing
      systems.
AB  - A number of online video sharing systems, out of which YouTube is the most
      popular, provide features that allow users to post a video as a response to a
      discussion topic. These features open opportunities for users to introduce
      polluted content, or simply pollution, into the system. For instance, spammers
      may post an unrelated video as response to a popular one, aiming at increasing
      the likelihood of the response being viewed by a larger number of users.
      Moreover, content promoters may try to gain visibility to a specific video by
      posting a large number of (potentially unrelated) responses to boost the rank of
      the responded video, making it appear in the top lists maintained by the system.
      Content pollution may jeopardize the trust of users on the system, thus
      compromising its success in promoting social interactions. In spite of that, the
      available literature is very limited in providing a deep understanding of this
      problem. In this paper, we address the issue of detecting video spammers and
      promoters. Towards that end, we first manually build a test collection of real
      YouTube users, classifying them as spammers, promoters, and legitimate users.
      Using our test collection, we provide a characterization of content, individual,
      and social attributes that help distinguish each user class. We then investigate
      the feasibility of using supervised classification algorithms to automatically
      detect spammers and promoters, and assess their effectiveness in our test
      collection. While our classification approach succeeds at separating spammers and
      promoters from legitimate users, the high cost of manually labeling vast amounts
      of examples compromises its full potential in realistic scenarios. For this
      reason, we further propose an active learning approach that automatically chooses
      a set of examples to label, which is likely to provide the highest amount of
      information, drastically reducing the amount of required training data while
      maintaining comparable classification effectiveness.

PMID- 22147306
TI  - Detection of sudden pedestrian crossings for driving assistance systems.
AB  - In this paper, we study the problem of detecting sudden pedestrian crossings to
      assist drivers in avoiding accidents. This application has two major
      requirements: to detect crossing pedestrians as early as possible just as they
      enter the view of the car-mounted camera and to maintain a false alarm rate as
      low as possible for practical purposes. Although many current sliding-window
      based approaches using various features and classification algorithms have been
      proposed for image-/video-based pedestrian detection, their performance in terms
      of accuracy and processing speed falls far short of practical application
      requirements. To address this problem, we propose a three-level coarse-to-fine
      video-based framework that detects partially visible pedestrians just as they
      enter the camera view, with low false alarm rate and high speed. The framework is
      tested on a new collection of high-resolution videos captured from a moving
      vehicle and yields a performance better than that of state-of-the-art pedestrian
      detection while running at a frame rate of 55 fps.

PMID- 22147307
TI  - Pharmacokinetics of xanthohumol and metabolites in rats after oral and
      intravenous administration.
AB  - SCOPE: Xanthohumol (XN), a dietary flavonoid found in hops, may have health
      protective actions against cardiovascular disease and type 2 diabetes. Yet, there
      are limited data on the pharmacokinetics (PK) of XN. This study provides PK
      parameters for XN and its major metabolites in rats. METHODS AND RESULTS: A PK
      study was conducted in male jugular vein-cannulated Sprague-Dawley rats. Rats (n
      = 12/group) received an intravenous (IV) injection (1.86 mg/kg BW) or an oral
      gavage of a low (1.86 mg/kg BW), medium (5.64 mg/kg BW), or high (16.9 mg/kg BW)
      dose of XN. Plasma samples were analyzed for XN and its metabolites using LC
      MS/MS. The maximum concentration (C(max) ) and area under the curve (AUC(0-96 h)
      ) of total XN (free and conjugated) were 2.9+/-0.1 mg/L and 2.5+/-0.3 h*  mg/L in
      IV group, 0.019+/-0.002 mg/L and 0.84+/-0.17 h*  mg/L in the oral low group,
      0.043+/-0.002 mg/L and 1.03+/-0.12 h*  mg/L in the oral medium group, and 0.15+/
      0.01 mg/L and 2.49+/-0.10 h*  mg/L in the oral high group. CONCLUSION: The
      bioavailability of XN is dose-dependent and approximately 0.33, 0.13, and 0.11 in
      rats, for the low-, medium-, and high-dose groups, respectively.

PMID- 22147308
TI  - Laminar expression of ephrin-A2 in primary somatosensory cortex of postnatal
      rats.
AB  - Several Eph receptors, prominently EphA4 and EphA7, and their corresponding
      ligands are known to influence neocortical development, including topographic
      sorting of thalamocortical axons within primary somatosensory cortex (SI). This
      study investigated postnatal expression of a ligand that can bind to these
      receptors, ephrin-A2. Quantitative methods revealed that expression of ephrin-A2
      mRNA in SI reached maximum levels on postnatal day (P) 4 and dropped thereafter
      to background by P18. Ephrin-A2 mRNA expression assessed by in situ hybridization
      qualitatively revealed a similar time course and localized the expression pattern
      primarily in two broad laminae in SI, comprising the supragranular and
      infragranular layers, and with additional expression in the subplate. This
      expression pattern was investigated in greater detail using immunohistochemistry
      for ephrin-A2 protein. Immunoreactivity generally showed the same laminar
      distribution as seen with in situ hybridization, except that it persisted longer,
      lasting to approximately P14. Expression in the cortical plate was low or absent
      within presumptive layer IV, and it remained so as cortical lamination
      progressed. Double-labeling immunohistochemistry with confocal microscopy
      revealed that cortical neurons were the principal elements expressing ephrin-A2
      protein. These findings are consistent with possible involvement of ephrin-A2, in
      concert with one or more Eph receptors, in influencing arbor development of
      thalamocortical axons at cortical layer IV boundaries.

PMID- 22147309
TI  - Nutritional status of children and young adults with Ewing sarcoma or
      osteosarcoma at diagnosis and during multimodality therapy.
AB  - OBJECTIVE: Objective of our study was to evaluate the nutritional status and
      growth of children and adolescents with common malignancies of the
      musculoskeletal system at diagnosis, and undergoing multimodality therapy.
      METHODS: A retrospective analysis of data from 2001 to 2009 was conducted.
      Hospital charts were used as a source of clinical data. Primary endpoint of the
      analyses was to identify variations in anthropometric parameters at diagnosis and
      during the first 2 years of follow-up in children and adolescents with
      osteosarcoma or Ewing sarcoma. Factors contributing to disorders of growth in
      this population were sought. RESULTS: A total of 139 children were registered, 62
      with Ewing sarcoma and 77 with osteosarcoma. At diagnosis 72.7% of all patients
      were classified as adequately nourished (BMI 5th to <85th percentiles). During
      treatment all anthropometric parameters were markedly reduced (P < 0.001) in both
      groups with extreme changes in body weight from -30% to +44%. This was pronounced
      in children affected by osteosarcoma (P < 0.05). During follow-up, recovery of
      body weight was noted in both groups. Height Z-scores remained low (P < 0.001) in
      comparison to the general population. After the observation period 43.4% of the
      children with osteosarcoma and 25.5% of the patients with Ewing sarcoma
      demonstrated an altered body mass. CONCLUSIONS: Pediatric patients with Ewing
      sarcoma or osteosarcoma are at an increased risk for developing malnutrition, in
      the form of either over- or underweight during multimodality therapy. Early
      recognition of abnormal body mass is required to prevent and to treat long-term
      comorbidities caused by malnutrition.

PMID- 22147310
TI  - Fetal haemoglobin Bart's disease in Hong Kong: why early diagnosis could not be
      made.

PMID- 22147311
TI  - Re-emergence of late presentations of fetal haemoglobin Bart's disease in Hong
      Kong.
AB  - OBJECTIVES: To compare early and late presentations of fetal haemoglobin Bart's
      disease in the Kowloon West Cluster in Hong Kong, and to find reasons for the re
      emergence of late presentations. DESIGN: Case series with internal comparisons.
      SETTING: Two tertiary obstetric units in Hong Kong. PATIENTS: All cases with
      confirmed diagnosis of fetal haemoglobin Bart's disease from 1 January 2000 to 31
      December 2009. MAIN OUTCOME MEASURES:  PRIMARY OUTCOME: antenatal care in the
      current pregnancy. SECONDARY OUTCOMES: clinical presentations, ultrasound
      features, and pregnancy outcomes. RESULTS: A total of 59 cases (46 early
      presentations and 13 late presentations) of fetal haemoglobin Bart's disease were
      identified during the study period. All the late presentations were identified
      from year 2003 onwards. Late presentations were significantly associated with non
      eligible obstetric patients (69% vs 11%; P<0.001), non-booked status at our
      antenatal service (62% vs 0%; P<0.001), and unavailability of partner's mean
      corpuscular volume status (23% vs 0%; P=0.009). Mothers presenting late were more
      likely to have symptoms or signs (85% vs 0%; P<0.001) and to suffer from
      gestational hypertensive disorder (54% vs 0%; P<0.001). Ultrasound features of
      these pregnancies included cardiomegaly (94%), placentomegaly (98%), and hydrops
      fetalis (77%). All pregnancies presenting early were either legally terminated or
      miscarried. The perinatal mortality in late presentations was 85%. CONCLUSION:
      The re-emergence of late presentations of fetal haemoglobin Bart's disease after
      2003 was related to influx of non-eligible obstetric patients without proper
      antenatal screening and diagnosis of thalassaemia. Maternal low mean corpuscular
      volume and characteristic prenatal ultrasound features such as cardiomegaly,
      placentomegaly, and hydrops fetalis are useful for detecting affected pregnancies
      in this group of patients. Better education of both patients and doctors is
      necessary to explain the importance of early diagnosis of the disease and the
      seriousness of complications due to late presentations, so as to reduce
      undesirable maternal and perinatal outcomes.

PMID- 22147312
TI  - Utility of a preoperative assessment clinic in a tertiary care hospital.
AB  - OBJECTIVES: To assess the utilisation rate of a preoperative assessment clinic
      and its impact on length of stay and discharge destinations. DESIGN:
      Retrospective case series with internal comparisons. SETTING: A tertiary hospital
      in Hong Kong. PATIENTS: All medical records of elective surgical admissions to a
      hospital in Hong Kong from April to June 2008 were retrieved. Medical records of
      patients who did not attend the preoperative assessment clinic were further
      reviewed by surgeons to assess if the patients could have been referred to the
      clinic. MAIN OUTCOME MEASURES: Total length of stay, preoperative and
      postoperative length of stay, and the discharge destinations of the patients
      attending and not attending the clinic were compared. RESULTS. In all, 640
      patients underwent elective operations, of whom 22 (3%) patients were seen in the
      preoperative assessment clinic. In patients who had a major operation, the mean
      (standard deviation) total length of stays for clinic attenders and non-attenders
      were: 5.2 (3.6) versus 13.2 (18.8) days (P<0.001). The respective figures for
      preoperative and postoperative length of stay were: 1.3 (2.3) versus 4.5 (8.9)
      days (P=0.001), and 3.9 (2.9) versus 8.7 (14.5) days (P<0.001). For patients who
      had an intermediate operation, the respective mean (standard deviation) length of
      hospital stays were 2.4 (2.0) versus 7.3 (13.9) days (P=0.002) and the figures
      for postoperative length of stays were 1.3 (0.5) versus 4.5 (9.3) days (P=0.001).
      Surgeons had classified 108 (17%) of the cases as possible preoperative
      assessment clinic users. Among the latter, 71 (66%) had no special reason to stay
      in the hospital. The discharge destination was not associated with the use of
      preoperative assessment clinic for patients having major (Chi squared=0.18,
      P=0.912) or intermediate (Chi squared=0.34, P=0.468) operations. CONCLUSION:
      Successful implementation of preoperative assessment clinic service requires
      close collaboration between surgeons, anaesthetists, clinicians, and also the re
      engineering of health service delivery.

PMID- 22147313
TI  - Utilisation and outcome of renal replacement therapy in an Asian tertiary
      intensive care unit.
AB  - OBJECTIVES: To determine the period prevalence, demographic characteristics, cost
      of treatment, and outcomes of patients admitted to the intensive care unit for
      continuous renal replacement therapy. DESIGN: Descriptive case series. SETTING:
      Intensive Care Unit in a Hong Kong tertiary referral, teaching hospital.
      PATIENTS: All patients admitted to the Intensive Care Unit from January to
      December 2007 who underwent continuous renal replacement therapy. MAIN OUTCOME
      MEASURES: Period prevalence of continuous renal replacement therapy, patient
      demographic data, referral sources by specialty and hospital location, diagnosis,
      daily cost of disposable items, duration of renal replacement therapy, intensive
      care unit length of stay, and hospital mortality. RESULTS: Of 1652 patients
      admitted to the intensive care unit over a 12-month period, 131 (8%) underwent
      continuous renal replacement therapy, of whom 56% were admitted from general
      wards (the department of medicine being the source of 59% of referrals). The
      median age of these continuous renal replacement therapy patients was 67
      (interquartile range, 55-76) years, with a slight male predominance (66%). The
      mean APACHE II score of the patients was 29 (standard deviation, 7). Chronic
      renal failure requiring either haemodialysis or peritoneal dialysis was present
      in 20/131 (15%) patients. Sepsis was the diagnosis most commonly associated with
      renal failure deemed to warrant continuous renal replacement therapy (43%). The
      median duration of such continuous therapy was 55 (interquartile range, 25-93)
      hours and the median intensive care unit length of stay was 120 (interquartile
      range, 51-289) hours. The mean daily cost of disposables for the provision of
      continuous renal replacement therapy was HK$3510. The overall intensive care unit
      mortality of patients having continuous renal replacement therapy was 38% and the
      hospital mortality was 53%. The corresponding rates for patients with acute renal
      failure were 45% and 56%, respectively. Patients undergoing continuous renal
      replacement therapy had prolonged intensive care unit stays (120 vs 24 hours;
      P<0.05) and higher corresponding hospital mortality rates (53% vs 20%; P<0.001)
      compared to those not having such therapy. CONCLUSION: The 8% period prevalence
      of patients admitted to the intensive care unit undergoing continuous renal
      replacement therapy was somewhat higher than in recently published reports in the
      international literature. However intensive care unit and hospital mortality
      rates for such patients were lower than previously reported. The corresponding
      total daily cost of relevant disposables was similar to costs reported
      internationally, whilst the length of intensive care unit stays for our cohort
      were relatively short.

PMID- 22147314
TI  - Intracranial electroencephalogram to evaluate refractory temporal and frontal
      lobe epilepsy.
AB  - OBJECTIVE: We undertook a collaborative study in a multidisciplinary team to
      channel refractory epilepsy patients to test a hypothesis about placement of
      intracranial electroencephalography arrays. DESIGN: This was a descriptive case
      series. Prospective non-invasive presurgical evaluations were based on clinical
      semiology, magnetic resonance imaging, video-electroencephalography findings and
      neuropsychological assessments. If the results were discordant, a hypothesis was
      generated using individualised combinations of positron emission tomography,
      single-photon emission computed tomography, functional magnetic resonance imaging
      and Wada tests. The indications for intracranial electroencephalography were: (a)
      focal magnetic resonance imaging, ictal/interictal scalp electroencephalography
      with variable results (group A); (b) multi-focal magnetic resonance imaging,
      focal/multi-focal ictal scalp electroencephalography (group B); (c) non-lesional
      magnetic resonance imaging, focal/multi-focal ictal scalp electroencephalography
      (group C). We evaluated whether the seizure-onset zones and eloquent areas were
      delineated, surgical outcomes (if operated on), and pathology results. SETTING: A
      tertiary referral centre for neurology in Hong Kong. PATIENTS: A total of 105
      refractory epilepsy patients completed non-invasive presurgical evaluations over
      the period 2007 to 2009. Thirty-two patients were eligible for direct resective
      surgery, and another 25 patients had a testing hypothesis formulated. Of these 25
      patients, 10 were eligible for intracranial electroencephalography based on
      technical/financial considerations. RESULTS: All 10 patients (group A=2, group
      B=4, group C=4) had their epileptogenic zones defined. Six patients underwent
      functional mapping, all of whom had their eloquent areas defined. Seven of the 10
      patients underwent resective surgery; four of them achieved Engel class I/II
      outcomes. The dichotomised outcomes were 100% (group A), 50% (group B), and 33%
      (group C) achieving Engel class I/II. Two patients had asymptomatic subdural
      haematoma. There was no intracranial infection or operative mortality. In five
      (71%) of seven of the patients, a histological diagnosis was established.
      CONCLUSION: Proper deployment of intracranial electroencephalography is useful in
      the presurgical evaluation of patients with refractory epilepsy. This modality of
      management is potentially of benefit for patients with refractory epilepsy, but
      is underutilised locally.

PMID- 22147315
TI  - Development of the Chinese version of the Paediatric Allergic Disease Quality of
      Life Questionnaire: reliability and validity.
AB  - OBJECTIVE: Paediatric Allergic Disease Quality of Life Questionnaire is a health
      related assessment tool designed for children with allergic diseases. This study
      aimed to translate the original English version of the Questionnaire to Chinese
      and to provide psychometric evidence on the validity and reliability of the
      translated version. DESIGN: Cross-sectional study. SETTING: Out-patient clinic of
      a non-teaching hospital in Hong Kong. PARTICIPANTS: The Paediatric Allergic
      Disease Quality of Life Questionnaire was translated to Chinese and then
      completed by a group of 115 Hong Kong Chinese children (66 male and 49 female;
      mean age, 11 years) with allergic disease(s). All subjects were asked to respond
      using visual analogue scales dealing with issues related to the perceived
      morbidity of allergic diseases. To assess test-retest reliability, 2 weeks later
      a subgroup of 16 individuals was retested with the same Questionnaire. RESULTS:
      The internal consistency of the Chinese Paediatric Allergic Disease Quality of
      Life Questionnaire was satisfactory (Cronbach alpha=0.92). The correlation
      between the total Questionnaire score and the visual analogue scale score was
      moderately significant (Spearman's rho=0.49; 95% confidence interval, 0.34-0.62).
      Structural validity as studied by confirmatory factor analysis found that the
      structure of subscales was remarkably similar to the original English version.
      The intra-class correlation between the Questionnaire score from the first and
      the second test in the subgroup of 16 subjects was 0.75, indicating adequate
      repeatability. CONCLUSION: The validity and reliability of the Chinese version of
      the Paediatric Allergic Disease Quality of Life Questionnaire was established for
      clinical use.

PMID- 22147316
TI  - Single-incision laparoscopic cholecystectomy: from four wounds to one.
AB  - OBJECTIVE: To review the initial results and surgical outcomes of single-incision
      laparoscopic cholecystectomy. DESIGN: Prospective case series. SETTING: A
      university teaching hospital and a regional hospital in Hong Kong. PATIENTS: All
      patients undergoing single-incision laparoscopic cholecystectomy from August 2009
      to March 2011. RESULTS: Fifty patients underwent single-incision laparoscopic
      cholecystectomy during the study period. The indications for surgery included
      symptomatic gallstones (n=43) and gallbladder polyps (n=7). The mean operating
      time was 78 (standard deviation, 24) minutes. Forty-five of the patients
      successfully underwent single-incision laparoscopic cholecystectomy, giving a
      success rate of 90%. In the remaining five patients, additional working ports
      were constructed to obtain better exposure and dissection around Calot's
      triangle. On comparing the results of the initial 25 cases to the subsequent 25
      cases, in the latter group the operating time was significantly shorter (86 vs 71
      minutes; P=0.02), and the success rate was higher (80% vs 100%; P=0.05). During
      the median follow-up period of 6.8 months, four patients had complications, which
      included: postoperative urinary retention (n=2), one each with a haematoma and an
      incisional hernia. No patient endured bile duct injury, postoperative bile
      leakage, or haemorrhage in our series. CONCLUSION: Single-incision laparoscopic
      cholecystectomy is feasible and safe for treatment of uncomplicated gallbladder
      diseases. There was a reduction in the operating time and increase in success
      rate with accumulation of experience. Nevertheless, surgeons should be cautious
      about the potential risks of this new technique.

PMID- 22147317
TI  - Secondary prevention of stroke: an evidence-based clinical audit in the primary
      care.
AB  - OBJECTIVE: To audit secondary preventive care in non-acute stroke patients in a
      local General Outpatient Clinic of the Hospital Authority. DESIGN: Comparison of
      two samples from a case series at different time-points. SETTING: General
      Outpatient Clinic, Hong Kong. PATIENTS: Non-acute stroke patients fulfilling the
      inclusion criteria and regularly followed up in a local General Outpatient Clinic
      during the audit cycle were recruited. Evidence-based audit criteria and
      performance standards were established after thorough literature review. A sample
      from this case series was compared retrospectively at two time-points. First
      phase evaluation was performed in October 2009 and deficiencies were identified.
      After 9 months of active intervention, second-phase evaluation was performed in
      July 2010. Chi squared test and student's t test were used to compare the
      significance of relevant changes noted. RESULTS: First-phase data showed marked
      deficiencies in proper assessment of cardiovascular risk factors. Satisfactory
      blood pressure, glucose and lipid control was evident only in 47% of the
      hypertensive, 45% of the diabetic, and 37% of the dyslipidaemic stroke patients,
      respectively. After 9 months of implementing changes, significant improvements
      were noted with respect to standard targets being achieved. In the second phase,
      more comprehensive tackling of cardiovascular risk factors was noted, with
      satisfactory blood pressure control in 73% of hypertensive patients, and adequate
      metabolic control in 62% diabetic patients (P<0.01 for both). Only 59% of the
      dyslipidaemic stroke patients had optimal lipid control, though their mean low
      density lipoprotein concentration was significantly reduced (P<0.05). CONCLUSION:
      This study provided a valuable lesson in identifying deficiencies in secondary
      prevention for stroke patients managed in a local primary care facility. Using a
      team approach intervention, quality assurance was promoted and a definite impact
      on patient care was demonstrated.

PMID- 22147318
TI  - Workshop 3--source of bias in case series, patient cohorts, and randomised
      controlled trials.

PMID- 22147319
TI  - The last defence? Surgical aspects of gouty arthritis of hand and wrist.
AB  - OBJECTIVE: To review the epidemiology, pathophysiology, clinical manifestations,
      diagnosis, and treatment of gouty arthritis of the hand and wrist, with a focus
      on the surgical aspects. DATA SOURCES AND EXTRACTION: Electronic databases
      including MEDLINE, PubMed, and the Cochrane library were searched with the key
      words of "gouty arthritis", "hand", "wrist", and "surgical". STUDY SELECTION: A
      total of 55 articles were selected for inclusion in this review. DATA SYNTHESIS:
      There is no existing study for the overall prevalence of gout in Asia, though one
      study showed that it was 3.1% in Taiwan. Its pathophysiology entails
      hyperuricaemia, trauma, lower temperatures, and previous diseases. Gouty
      arthritis of hand and wrist presents as acute wrist pain, subcutaneous or
      peritendinous tophi, tenosynovitis, entrapment neuropathy, tendon rupture, or
      even bone destruction. Demonstration of negatively birefringent crystals in the
      absence of organisms and a normal white cell count in synovial fluid confirm the
      diagnosis. Medical treatment including non-steroidal anti-inflammatory drugs,
      colchicines, allopurinol, uricosuric agents, and lifestyle modifications remain
      the mainstay of treatment. Surgical treatment options for tophaceous gout involve
      decompression by aspiration, incision and drainage, tenosynovectomy, shaving
      procedures, and complex surgical approach. CONCLUSION. While medical treatment
      remains the mainstay of treatment for gouty arthritis of the hand and wrist, 5%
      of patients may not respond. In this group, surgery is often performed in
      advanced stages, but yields less-than-satisfactory outcomes. Gouty arthritis is
      difficult to treat when it starts to cause stiffness and deformities. Although
      more studies are needed to evaluate the outcomes, the authors suggest that one
      possible solution is pre-emptive surgery.

PMID- 22147320
TI  - The use of sex hormones in women with rheumatological diseases.
AB  - A number of rheumatological diseases predominantly affect women of reproductive
      age. There has always been concern that the use of oestrogen-containing agents
      such as combined hormonal contraception and hormone therapy might aggravate these
      conditions. This article reviews the up-to-date evidence regarding the safety of
      using these agents in women with various rheumatological diseases, with emphasis
      on systemic lupus erythematosus and rheumatoid arthritis. In the absence of
      antiphospholipid antibody or other prothrombotic risk factors, combined hormonal
      contraception is not contra-indicated in most rheumatological conditions
      including inactive systemic lupus erythematosus. Moreover, hormone therapy is
      generally not contra-indicated except for women with active systemic lupus
      erythematosus disease where its effect on disease flare is less clear and
      individual judgement is required.

PMID- 22147321
TI  - An unusual cause of retention of urine after intravesical Bacillus Calmette
      Guerin therapy for superficial bladder cancer.
AB  - We report an unusual complication of intravesical Bacillus Calmette-Guerin
      therapy for superficial bladder cancer, namely, retention of urine secondary to
      prostatic Bacillus Calmette-Guerin infection and abscess. A summary of the
      literature together with a review of its management is discussed.

PMID- 22147322
TI  - Disseminated amyloidosis presenting with right proximal femur pathological
      fracture in a haemodialysis end-stage renal failure patient.
AB  - Osteoarticular amyloidosis can be one of the musculoskeletal system
      manifestations related to dialysis. We share our experience in dealing with a
      case of disseminated haemodialysis-associated amyloidosis in a 74-year-old end
      stage renal failure patient. This patient suffered from a serious complication,
      namely an unprovoked pathological fracture at the basal neck region of the right
      femur. Polyarticular cystic and lytic lesions over the contralateral proximal
      femur, bilateral proximal humerus and the right lunate were noted on further
      imaging. In view of extensive amyloidotic infiltration into the proximal femur as
      well as the acetabulum, a cemented total hip arthroplasty operation was performed
      for pain relief and restoration of function. The radiological investigations,
      diagnostic challenges, operative as well as histopathological findings are
      discussed. This disease should be considered in the differential diagnosis of
      pathological juxta-articular fracture in patients undergoing haemodialysis.

PMID- 22147323
TI  - Genetic diagnosis of severe myoclonic epilepsy of infancy (Dravet syndrome) with
      SCN1A mutations in the Hong Kong Chinese patients.
AB  - Epilepsy is a clinically and genetically heterogeneous group of disorders. The
      advent of molecular genetics brings unprecedented advancement in diagnostic
      molecular pathology and reduces over-reliance on traditional clinical
      classification. Severe myoclonic epilepsy of infancy or Dravet syndrome is a
      catastrophic infantile-onset epilepsy. We report two unrelated Hong Kong Chinese
      patients with this condition presenting with febrile seizures, epilepsy with
      different semiologies, psychomotor retardation, and recurrent status epilepticus.
      Two different mutations were characterised, viz NM_001165963.1: c.680T>G;
      NP_001159435.1: p.I227S and NM_001165963.1: c.3953T>G; NP_001159435.1: p.L1318R
      (novel). Genetic characterisation conveys a definitive diagnosis and is important
      from the perspective of selecting anti-epileptic drug therapy and genetic
      counselling.

PMID- 22147324
TI  - Gastric melanoma.

PMID- 22147325
TI  - An unusual cause for weight loss and diabetes.

PMID- 22147327
TI  - Commentary on the article "Intracranial aneurysms in twins: case report and
      review of the literature".

PMID- 22147326
TI  - A biography of arsenic and medicine in Hong Kong and China.
AB  - Arsenic trioxide has been used in traditional Chinese medicine for over 5000
      years, but lost its appeal due to its toxicity. It was rediscovered in western
      medicine and enjoyed a renaissance from 1830 to 1930, as the first effective
      chemotherapy against syphilis, parasites and leukaemia. These years were also a
      time of political turmoil in China. The Nanking treaty (29 August 1842) turned
      Hong Kong into a colony, while the Xinhai Revolution (10 October 1911) gave birth
      to a republic of China. Arsenic returned to China and Hong Kong with the
      establishment of the first medical schools from 1887 to 1920. Until 1950, oral
      arsenic trioxide was the standard anti-leukaemic treatment in Queen Mary
      Hospital. The advent of alkylating chemotherapeutic agents replaced arsenic
      trioxide in Hong Kong and around the world. In the 1970s, however, the specific
      activity of arsenic trioxide against acute promyelocytic leukaemia was re
      discovered during the Cultural Revolution in Harbin, China. In 1997, Hong Kong
      was returned to China. In the same year, arsenic trioxide returned to the world
      stage. Intravenous arsenic trioxide became the worldwide standard therapy for
      relapsed acute promyelocytic leukaemia. Oral administration of arsenic trioxide
      was revived in Hong Kong in 2000. This resulted in the first locally produced,
      registered, patented prescription drug in Hong Kong. Pending imminent
      manufacture, this product is poised to revolutionise acute promyelocytic
      leukaemia care and may hold the key to saving the lives of acute promyelocytic
      leukaemia patients worldwide. The remarkable journey of arsenic in the setting of
      medical history of China and Hong Kong is reviewed.

PMID- 22147328
TI  - Moxifloxacin relieves the persistent symptoms of lower urinary tract after
      cessation of ketamine abuse.

PMID- 22147329
TI  - Management of mercury exposure in Hong Kong Poison Centre.

PMID- 22147330
TI  - Malpractice claims: corrections.

PMID- 22147331
TI  - Numerical characterization and modeling of subject-specific ultrawideband body
      centric radio channels and systems for healthcare applications.
AB  - The paper presents a subject-specific radio propagation study and system modeling
      in wireless body area networks using a simulation tool based on the parallel
      finite-difference time-domain technique. This technique is well suited to model
      the radio propagation around complex, inhomogeneous objects such as the human
      body. The impact of different digital phantoms in on-body radio channel and
      system performance was studied. Simulations were performed at the frequency of 3
      10 GHz considering a typical hospital environment, and were validated by on-site
      measurements with reasonably good agreement. The analysis demonstrated that the
      characteristics of the on-body radio channel and system performance are subject
      specific and are associated with human genders, height, and body mass index.
      Maximum variations of almost 18.51% are observed in path loss exponent due to
      change of subject, which gives variations of above 50% in system bit error rate
      performance. Therefore, careful consideration of subject-specific parameters are
      necessary for achieving energy efficient and reliable radio links and system
      performance for body-centric wireless network.

PMID- 22147332
TI  - Subject-specific estimation of central aortic blood pressure using an
      individualized transfer function: a preliminary feasibility study.
AB  - This paper presents a new approach to the estimation of unknown central aortic
      blood pressure waveform from a directly measured peripheral blood pressure
      waveform, in which a physics-based model is employed to solve for a subject- and
      state-specific individualized transfer function (ITF). The ITF provides the means
      to estimate the unknown central aortic blood pressure from the peripheral blood
      pressure. Initial proof-of-principle for the ITF is demonstrated experimentally
      through an in vivo protocol. In swine subjects taken through wide range of
      physiologic conditions, the ITF was on average able to provide central aortic
      blood pressure waveforms more accurately than a nonindividualized transfer
      function. Its usefulness was most evident when the subject's pulse transit time
      deviated from normative values. In these circumstances, the ITF yielded
      statistically significant reductions over a nonindividualized transfer function
      in the following three parameters: 1) 30% reduction in the root-mean-squared
      error between estimated versus actual central aortic blood pressure waveform (p <
      10 (-4)), 2) >50% reduction in the error between estimated versus actual systolic
      and pulse pressures ( p < 10 (-4)), and 3) a reduction in the overall breakdown
      rate (i.e., the frequency of estimation errors >3 mmHg, p < 10 (-4)). In
      conclusion, the ITF may offer an attractive alternative to existing methods that
      estimates the central aortic blood pressure waveform, and may be particularly
      useful in nonnormative physiologic conditions.

PMID- 22147333
TI  - Effects of wastewater irrigation on chemical and physical properties of
      Petroselinum crispum.
AB  - The present study was carried out to assess the impact of wastewater on parsley
      (Petroselinum crispum). The parameters determined for soil were pH, electrical
      conductivity (EC), soil organic matter (SOM), nutrient elements (Ca, Mg, Na, K,
      Mn, Cu, Zn, and Fe), and heavy metals (Cd, Cr, Ni, and Pb), while the parameters
      determined for the plant included pigment content, dry matter, nutrient element,
      and heavy metals. SOM, EC, and clay contents were higher, and pH was slightly
      acidic in soil treated with wastewater compared to control soil. The enrichment
      factors (EF) of the nutrient elements in contaminated soil are in the sequence of
      Na (2) > Ca (1.32) > Mn = Mg (1.17) > Cu (1.11) > Zn (1.08) > Fe (1.07) > K
      (0.93), while EF in parsley are Na (6.63) > Ca (1.60) > Mg (1.34) > Zn (1.15) >
      Fe (0.95) > Cu = K (0.90) > Mn (0.85). Application of wastewater significantly
      decreased dry matter, while photosynthetic pigment content increased in parsley.
      The enrichment of the heavy metals is in the sequence: Cd (1.142) > Pb (1.131) >
      Ni (1.112) > Cr (1.095). P. crispum shows a high transfer factor (TF > 1) for Cd
      signifying a high mobility of Cd from soil to plant. Thus, although the
      wastewater irrigation in parsley production aims to produce socioeconomic
      benefits, study results indicated that municipal wastewater is not suitable for
      irrigation of parsley because it has negative effects on plant and causes heavy
      metal accumulation.

PMID- 22147334
TI  - Modified natural clinoptilolite detoxifies small mammal's organism loaded with
      lead I. Lead disposition and kinetic model for lead bioaccumulation.
AB  - Zeolites, especially clinoptilolites, have wide application in removing heavy
      metals from different solutions and wastewater. The detoxification capacity of
      the clinoptilolite sorbent KLS-10-MA, a modified natural Bulgarian zeolite,
      applied as a food supplement in conditions of an ecotoxicological experiment with
      conventional food and lead was demonstrated for the first time. Laboratory mice,
      inbred imprinting control region strain, were used in a 90-day ecotoxicological
      experiment. Animals were divided into four experimental groups. Lead
      bioaccumulations in exposed and non-supplemented/supplemented with KLS-10-MA
      animals were compared. As additional control, healthy animals non-exposed to Pb
      were fed with conventional forage mixed with 12.5% KLS-10-MA. The dietary
      inclusion of the sorbent reduced Pb concentrations in exposed and supplemented
      mice by 84%, 89%, 91%, 77%, and 88% in carcass, liver, kidneys, bones, and feces,
      respectively. A mathematical model was proposed to outline the common trends of
      bone Pb bioaccumulation in exposed and non-supplemented/supplemented animals.
      Characteristic parameters of the kinetics of Pb concentrations were determined.
      Based on the model, the coefficient of absorption of Pb by gastrointestinal
      mucosa in the supplemented mice was found-eta = 3.53% (versus eta = 15% in non
      supplemented ones). The present study clearly indicates that there is a realistic
      perspective to create a new drug based on modified natural clinoptilolites in
      cases of chronic heavy metal intoxication, without negatively affecting the
      environment.

PMID- 22147335
TI  - Introducing students to cancer prevention careers through programmed summer
      research experiences.
AB  - Training programs in cancer prevention research play an important role in
      addressing impending shortages in the cancer prevention workforce. Published
      reports on the effectiveness of these programs, however, often focus on a
      program's success in recruiting and retaining a demographically diverse trainee
      population or on academic successes of the trainees, in general. Little has been
      reported about programs' success in stimulating long-term interest in cancer
      prevention per se, whether in research or in other choATsen applications. We set
      out to examine the success of our National Cancer Institute (NCI) R25E American
      Recovery and Reinvestment Act (ARRA)-funded summer research experiences program
      for undergraduates at fostering awareness of and career interest in cancer
      prevention. Fourteen summer research undergraduates participated in a 12-week
      structured training program which featured a variety of experiences designed to
      create awareness of and interest in cancer prevention and cancer prevention
      research as career tracks. Experiences included career talks by faculty,
      informational interviewing of role model faculty, career exploration workshops,
      and structured interactions with graduate students, postdoctoral fellows, and
      junior faculty. Students were surveyed about the effectiveness of the program via
      SurveyMonkey 8 months after completing the program. This article reports on the
      results of the survey and analyzes the relative effectiveness of the various
      types of programming strategies used. Implications for use in training program
      development are discussed.

PMID- 22147337
TI  - Recent advances in the application of capillary electromigration methods for food
      analysis and Foodomics.
AB  - The analysis of food components using capillary electromigration methods is
      reviewed in this work. Papers that were published from February 2009 to February
      2011 are included following the previous review by Herrero et al.
      (Electrophoresis, 2010, 31, 205-228). The analysis of amino acids, biogenic
      amines, peptides, proteins, DNAs, carbohydrates, phenols, polyphenols, pigments,
      toxins, pesticides, vitamins, additives, small organic and inorganic ions and
      other compounds found in foods and beverages are reviewed, as well as those
      applications of CE for monitoring food interactions and food processing. The use
      of microchips, CE-MS and chiral-CE in food analysis is also discussed as well as
      other current and foreseen trends in this area of research including new
      developments in Foodomics.

PMID- 22147336
TI  - Measuring the success of community science: the northern California Household
      Exposure Study.
AB  - BACKGROUND: Environmental health research involving community participation has
      increased substantially since the National Institute of Environmental Health
      Sciences (NIEHS) environmental justice and community-based participatory research
      (CBPR) partnerships began in the mid-1990s. The goals of these partnerships are
      to inform and empower better decisions about exposures, foster trust, and
      generate scientific knowledge to reduce environmental health disparities in low
      income, minority communities. Peer-reviewed publication and clinical health
      outcomes alone are inadequate criteria to judge the success of projects in
      meeting these goals; therefore, new strategies for evaluating success are needed.
      OBJECTIVES: We reviewed the methods used to evaluate our project, "Linking Breast
      Cancer Advocacy and Environmental Justice," to help identify successful CBPR
      methods and to assist other teams in documenting effectiveness. Although our
      project precedes the development of the NIEHS Evaluation Metrics Manual, a schema
      to evaluate the success of projects funded through the Partnerships in
      Environmental Public Health (PEPH), our work reported here illustrates the record
      keeping and self-reflection anticipated in NIEHS's PEPH. DISCUSSION: Evaluation
      strategies should assess how CBPR partnerships meet the goals of all partners.
      Our partnership, which included two strong community-based organizations,
      produced a team that helped all partners gain organizational capacity.
      Environmental sampling in homes and reporting the results of that effort had
      community education and constituency-building benefits. Scientific results
      contributed to a court decision that required cumulative impact assessment for an
      oil refinery and to new policies for chemicals used in consumer products. All
      partners leveraged additional funding to extend their work. CONCLUSIONS: An
      appropriate evaluation strategy can demonstrate how CBPR projects can advance
      science, support community empowerment, increase environmental health literacy,
      and generate individual and policy action to protect health.

PMID- 22147338
TI  - TRAP, a powerful and versatile framework for gallium-68 radiopharmaceuticals.

PMID- 22147340
TI  - Molecular (nano) magnets as test grounds of quantum mechanics.

PMID- 22147342
TI  - The good taste of peptides.
AB  - The taste of peptides is seldom one of the most relevant issues when one
      considers the many important biological functions of this class of molecules.
      However, peptides generally do have a taste, covering essentially the entire
      range of established taste modalities: sweet, bitter, umami, sour and salty. The
      last two modalities cannot be attributed to peptides as such because they are due
      to the presence of charged terminals and/or charged side chains, thus reflecting
      only the zwitterionic nature of these compounds and/or the nature of some side
      chains but not the electronic and/or conformational features of a specific
      peptide. The other three tastes, that is, sweet, umami and bitter, are
      represented by different families of peptides. This review describes the main
      peptides with a sweet, umami or bitter taste and their relationship with food
      acceptance or rejection. Particular emphasis will be given to the sweet taste
      modality, owing to the practical and scientific relevance of aspartame, the well
      known sweetener, and to the theoretical importance of sweet proteins, the most
      potent peptide sweet molecules.

PMID- 22147343
TI  - Detection of doping with rhGH: excretion study with WADA-approved kits.
AB  - The detection of recombinant human growth hormone (rhGH) doping using the World
      Anti-Doping Agency (WADA) approved kits is reported in this research. Twenty-five
      young male students were selected and divided randomly into two groups with six
      belonging to the placebo and nineteen to the administration group. Thirteen
      volunteers in one group were administered with a Chinese preparation of rhGH
      while six volunteers included in the other group were given rhGH made in
      Switzerland. Both preparations were administered at a dose of 0.1 IU/kg body
      weight, one injection per day for 14 consecutive days. Blood samples were
      collected using WADA guidelines and all blood samples were analyzed with WADA
      approved Kits 1 and 2. The time window for detection of rhGH doping using WADA
      approved kits and criteria are discussed. Based on the comparison of the data
      obtained from this excretion study and from our routine (Chinese population as
      reference), consideration of the recent WADA criteria for rhGH AAF (Analytical
      Adverse Findings) is reported statistically. A comparison of data obtained from
      the two sample groups administered with pharmaceutical preparations, one Chinese
      rhGH (GenHeal(r), S19990019, 1.6 mg (4 IU), Shanghai, China) obtained from
      prokaryotic cells and the other (Saizen(r), S20080036, 1.33 mg (4 IU),
      Laboratoires Serone S.A., Switzerland) from eukaryotic cells is reported and did
      not show any significant difference for the detection of doping with rhGH.

PMID- 22147344
TI  - Oxidative stress is associated with genetic polymorphisms in one-carbon
      metabolism in coronary artery disease.
AB  - In view of growing body of evidence favouring the association of aberrations in
      one-carbon metabolism and oxidative stress in the aetiology of coronary artery
      disease (CAD), we investigated the risk associated with polymorphisms regulating
      the folate uptake and transport such as the glutamate carboxypeptidase II (GCPII)
      C1561T, reduced folate carrier 1 (RFC1) G80A and cytosolic serine
      hydroxymethyltransferase (cSHMT) C1420T. We further evaluated the impact of seven
      putatively functional polymorphisms of this pathway on oxidative stress markers.
      Genotyping was performed on 288 CAD cases and 266 healthy controls along with the
      dietary folate assessment. GCPII C1561T polymorphism was found to be an
      independent risk factor (OR 2.71, 95% CI 1.47-4.98) for CAD, whereas cSHMT C1420T
      conferred protection (OR 0.51, 95% CI 0.37-0.70). Oxidative stress markers like
      the plasma levels of malondialdehyde, protein carbonyls and 8-oxo-deoxyguanosine
      were significantly increased and total glutathione was significantly decreased in
      CAD cases. Elevated oxidative stress was observed in subjects carrying GCPII
      1561T and MTRR 66A-variant alleles and low oxidative stress was observed in the
      subjects carrying cSHMT 1420T and TYMS 5'-UTR 2R allele. GCPII C1561T, MTHFR
      C677T and MTRR A66G polymorphisms were observed to influence the homocysteine
      levels (P < 0.05). SHMT and TYMS variants were found to decrease oxidative stress
      by increasing the folate pool (r = 0.38, P = 0.003) and also by increasing the
      antioxidant status (r = 0.28, P = 0.03). Influence of dietary folate status was
      not observed. Overall, this study revealed elevated oxidative stress that was
      associated with the aberrations in one-carbon metabolism which could possibly
      influence the CAD risk. 

PMID- 22147345
TI  - Isochromosome 17q, MYC amplification and large cell/anaplastic phenotype in a
      case of medullomyoblastoma with extracranial metastases.
AB  - Medullomyoblastoma (MMB) is a rare variant of medulloblastoma, a member of the
      family of central nervous system (CNS) embryonal tumors. The outcome of standard
      therapy for CNS embryonal tumors is often unpredictable in the setting of MMB.
      Here, we present the clinical course and treatment of an almost 4-year-old girl
      with MMB that was characterized by MYC amplification, isochromosome 17q and large
      cell/anaplastic histopathology.

PMID- 22147346
TI  - Measurement of action potential generation in isolated canine left ventricular
      midmyocardial myocytes.
AB  - Proarrhythmic side effects are a major limitation during the drug development
      process for cardiac and non-cardiac compounds. Because changes in cardiac action
      potential (AP) are undesirable, the evaluation of the effects of test compounds
      on the AP is essential before advancing new compounds to clinical testing.
      However, an increase in repolarization duration alone is not always
      proarrhythmic, and newer surrogate markers have been suggested to better predict
      the occurrence of arrhythmia. Described in this unit is a protocol for assessing
      changes in AP duration in canine ventricular myocytes utilizing optical imaging
      techniques. This protocol can be used at an early stage of drug discovery due to
      its relatively fast throughput. Additionally, a protocol is presented for
      assessing the occurrence of after-depolarizations, as well as a novel parameter
      for proarrhythmic risk, beat-to-beat variability of repolarization. This protocol
      can be used at a later stage of the drug discovery process to assess
      proarrhythmic potential.

PMID- 22147347
TI  - Measurement of glucose uptake in cultured cells.
AB  - Facilitative glucose uptake transport systems are ubiquitous in animal cells and
      responsible for transporting glucose across the cell surface membrane. Evaluation
      of glucose uptake is crucial in the study of numerous diseases and metabolic
      disorders, such as myocardial ischemia, diabetes mellitus, and cancer. Methods
      for assessing glucose uptake into mammalian cells are detailed in this unit. The
      work is divided into four sections: (1) a brief overview of glucose uptake assays
      in cultured cells; (2) a method for measuring glucose uptake using radiolabeled 3
      O-methylglucose; (3) a method for measuring glucose uptake using radiolabeled 2
      deoxyglucose (2DG); and (4) an improved method for measuring 2DG-uptake using an
      enzymatic, fluorometric assay, eliminating the need for radiolabeled glucose
      analogs.

PMID- 22147348
TI  - In vitro opioid receptor assays.
AB  - Although opioid analgesics have been used for centuries, identification of opioid
      receptors and the ability of an opioid receptor antagonist to block natural pain
      processes prompted a search for endogenous opioid peptides. In vitro models were
      needed to characterize opioid activity in biological samples. The longitudinal
      muscle/myenteric plexus (LM/MP) of the guinea pig ileum was the classical in
      vitro assay system, but the development of the mouse vas deferens (MVD) assay
      provided another important model that could be employed. Both assays entail
      electrical stimulation of intramural nerves to produce muscle contractions of the
      target organ. The robust contractions of the LM/MP are inhibited by u and kappa
      opioid receptor agonists, while the more labile contractions of the MVD are
      inhibited by u, kappa, and delta opioid receptor agonists. These in vitro assay
      systems are useful for evaluating biological activity of unknown substances and
      studying the properties of drug tolerance and both are described in this unit.

PMID- 22147349
TI  - Overview of drug product development.
AB  - The process for developing drug delivery systems has evolved over the past two
      decades with more scientific rigor, involving a collaboration of various fields,
      i.e., biology, chemistry, engineering, and pharmaceutics. Drug products, also
      commonly known in the pharmaceutical industry as formulations or "dosage forms,"
      are used for administering the active pharmaceutical ingredient (API) for
      purposes of assessing safety in preclinical models, early- to late-phase human
      clinical trials, and for routine clinical/commercial use. This overview discusses
      approaches for creating small-molecule API dosage forms, from preformulation to
      commercial manufacturing.

PMID- 22147350
TI  - Research dissemination reports. Introductory editorial.

PMID- 22147351
TI  - Cost-effectiveness of Dermabond versus sutures for lacerated wound closure: a
      randomised controlled trial.

PMID- 22147352
TI  - Cost implication of team-based structured versus usual care for type 2 diabetic
      patients with chronic renal disease.

PMID- 22147353
TI  - Health-related quality of life assessment for Hong Kong Chinese children with
      cancer.

PMID- 22147354
TI  - Quality-adjusted life years: population-specific measurement of the quality
      component.

PMID- 22147355
TI  - Tuberculosis susceptibility genes in the chemokine cluster region of chromosome
      17 in Hong Kong Chinese.

PMID- 22147356
TI  - Identification of T-cell epitopes of SARS-coronavirus for development of peptide
      based vaccines and cellular immunity assessment methods.

PMID- 22147357
TI  - Pathogenesis of SARS coronavirus infection using human lung epithelial cells: an
      in vitro model.

PMID- 22147358
TI  - Animal reservoirs for SARS-like coronavirus in southern China.

PMID- 22147359
TI  - Risk of liver cancer in patients with hepatitis B or C.

PMID- 22147360
TI  - Hepatitis B virus X gene in the development of hepatocellular carcinoma.

PMID- 22147361
TI  - Bacterial adhesion-resistant poly(2-hydroxyethyl methacrylate) derivative for
      mammalian cell cultures.
AB  - In an attempting to find new biomaterials for mammalian cell culture, PHEMA
      derivatives with ester side groups are synthesized by one-step polymer-analogous
      reaction. These polymers show excellent antifouling properties against S.
      epidermidis and P. aeruginosa while their cytotoxicity and proliferation activity
      for HDF cell are on a similar level as commercially available TCPS. The
      interesting bioadhesion property is systematically correlated with surface
      properties of the PHEMA derivatives.

PMID- 22147362
TI  - Mammography screening and risk of breast cancer death: a population-based case
      control study.
AB  - BACKGROUND: Because the efficacy of mammography screening had been shown in
      randomized controlled trials, the focus has turned on its effectiveness within
      the daily practice. Using individual data of women invited to screening, we
      conducted a case-control study to assess the effectiveness of the Dutch
      population-based program of mammography screening. METHODS: Cases were women who
      died from breast cancer between 1995 and 2003 and were closely matched to five
      controls on year of birth, year of first invitation, and number of invitations
      before case's diagnosis. ORs and 95% confidence intervals (CI) for the
      association between attending either of three screening examinations prior to
      diagnosis and the risk of breast cancer death were calculated using conditional
      logistic regression and corrected for self-selection bias. RESULTS: We included
      755 cases and 3,739 matched controls. Among the cases, 29.8% was screen-detected,
      34.3% interval-detected, and 35.9% never-screened. About 29.5% of the never
      screened cases had stage IV tumor compared with 5.3% of the screen-detected and
      15.1% of the interval-detected cases. The OR (95% CIs), all ages (49-75 years),
      was 0.51 (0.40-0.66) and for the age groups 50-69, 50-75, and 70-75 years were
      0.61 (0.47-0.79), 0.52 (CI 0.41-0.67), and 0.16 (0.09-0.29), respectively.
      CONCLUSION: The study provides evidence for a beneficial effect of early
      detection by mammography screening in reducing the risk of breast cancer death
      among women invited to and who attended the screening. IMPACT: This is the first
      case-control study that accurately accounts for equal screening opportunity for
      both cases and matched controls by number of invitations before case's diagnosis.

PMID- 22147363
TI  - Dried blood spot samples for seroepidemiology of infections with human
      papillomaviruses, Helicobacter pylori, Hepatitis C Virus, and JC Virus.
AB  - BACKGROUND: To establish antibody analysis from dried blood spots (DBS) on filter
      paper for seroepidemiologic infection and cancer association studies, we analyzed
      data from a population-based study in Mongolia. METHODS: Using multiplex
      serology, we analyzed 985 paired DBS and serum samples from the same donors for
      antibodies to 12 different proteins from four groups of infectious agents: human
      papillomaviruses (HPV), Helicobacter pylori (H. pylori), hepatitis C virus (HCV),
      and JC polyomavirus (JCV). RESULTS: Quantitative antibody reactivities in serum
      and DBS showed good correlation, with median correlation coefficients (Pearson
      R(2)) of 0.88 (range, 0.80-0.90) for high-titer (i.e., H. pylori, HCV, JCV) and
      0.79 (range, 0.72-0.85) for low-titer antibodies (i.e., HPV). For high-titer
      antibodies, serum and DBS data were comparable (median slope of linear trend
      line, 1.14; range, 1.09-1.21), whereas for low-titer antibodies, DBS reactivities
      were lower than in serum (median slope, 0.54; range, 0.50-0.80). By extrapolating
      seropositivity cutoff points previously defined for serum to DBS, we found high
      agreement (>89% for all antigens) of dichotomized DBS and serum results and
      median kappa values for high- and low-titer antibodies of 0.86 and 0.78 (range,
      0.78-0.92 and 0.55-0.86), respectively. Epidemiologic associations with known
      risk factors for HPV antibodies were as strong for DBS as for serum. CONCLUSIONS:
      DBS provide a reliable alternative to serum or plasma for detection of antibodies
      against various pathogens by multiplex serology. IMPACT: DBS do not require blood
      centrifugation and allow storage and shipment at ambient temperature, thus
      facilitating field work for seroepidemiologic studies especially in environments
      with limited technical infrastructure.

PMID- 22147364
TI  - Breast cancer screening trends in the United States and ethnicity.
AB  - BACKGROUND: The study objectives were to compare and examine mammography use
      trends among ethnic/racial women in the context of United States Healthy People
      2010 goals. METHODS: We analyzed pooled, multistage probability sample data from
      the 1996-2007 Medical Expenditure Panel Survey. Included in the sample were
      female respondents of ages 40 to 75 years (N = 64,811) from six ethnic/racial
      groups (Black, White, Mexican, Other Latinas, Puerto Rican, and Cuban). The
      primary outcome was self-reported, past two-year mammography use consistent with
      screening practice guidelines. RESULTS: We found that for most U.S. women, the
      Healthy People 2010 mammography goal (70%) was achieved between 1996 and 2007.
      Puerto Rican and White women, respectively, had the highest mammography rates,
      and Black and Cuban women had rates that approached the 2010 goal. CONCLUSION:
      Mexican Latinas reported the lowest rates of past two-year mammography; however,
      factors enabling healthcare access markedly moderated this lower likelihood. From
      2000, Mexican Latinas' mammography use was markedly below (10%) the Healthy
      People 2010 goal and remained there for the duration. IMPACT: Our findings
      indicate that healthcare equity goals are attainable if efforts are made to reach
      a sizeable portion of vulnerable populations.

PMID- 22147365
TI  - Urinary bladder cancer risk factors in Egypt: a multicenter case-control study.
AB  - BACKGROUND: We investigated associations between tobacco exposure, history of
      schistosomiasis, and bladder cancer risk in Egypt. METHODS: We analyzed data from
      a case-control study (1,886 newly diagnosed and histologically confirmed cases
      and 2,716 age-, gender-, and residence-matched, population-based controls). Using
      logistic regression, we estimated the covariate-adjusted ORs and 95% confidence
      interval (CI) of the associations. RESULTS: Among men, cigarette smoking was
      associated with an increased risk of urothelial carcinoma (OR = 1.8; 95% CI, 1.4
      2.2) but not squamous cell carcinoma (SCC); smoking both water pipes and
      cigarettes was associated with an even greater risk for urothelial carcinoma (OR
      = 2.9; 95% CI, 2.1-3.9) and a statistically significant risk for SCC (OR = 1.8;
      95% CI, 1.2-2.6). Among nonsmoking men and women, environmental tobacco smoke
      exposure was associated with an increased risk of urothelial carcinoma. History
      of schistosomiasis was associated with increased risk of both urothelial
      carcinoma (OR = 1.9; 95% CI, 1.2-2.9) and SCC (OR = 1.9; 95% CI, 1.2-3.0) in
      women and to a lesser extent (OR = 1.4; 95% CI, 1.2-1.7 and OR = 1.4; 95% CI, 1.1
      1.7, for urothelial carcinoma and SCC, respectively) in men. CONCLUSIONS: The
      results suggest that schistosomiasis and tobacco smoking increase the risk of
      both SCC and urothelial carcinoma. IMPACT: This study provides new evidence for
      associations between bladder cancer subtypes and schistosomiasis and suggests
      that smoking both cigarettes and water pipes increases the risk for SCC and
      urothelial carcinoma in Egyptian men.

PMID- 22147366
TI  - Organic monoliths for hydrophilic interaction
      electrochromatography/chromatography and immunoaffinity chromatography.
AB  - This article is aimed at providing a review of the progress made over the past
      decade in the preparation of polar monoliths for hydrophilic interaction LC
      (HILIC)/capillary electrochromatography (HI-CEC) and in the design of immuno
      monoliths for immunoaffinity chromatography that are based on some of the polar
      monolith precursors used in HILIC/HI-CEC. In addition, this review article
      discusses some of the applications of polar monoliths by HILIC and HI-CEC, and
      the applications of immuno-monoliths. This article is by no means an exhaustive
      review of the literature; it is rather a survey of the recent progress made in
      the field with 83 references published in the past decade on the topics of HILIC
      and immunoaffinity chromatography monoliths.

PMID- 22147367
TI  - Disclosing pathogenic genetic variants to research participants: quantifying an
      emerging ethical responsibility.
AB  - There is an emerging consensus that when investigators obtain genomic data from
      research participants, they may incur an ethical responsibility to inform at-risk
      individuals about clinically significant variants discovered during the course of
      their research. With whole-exome sequencing becoming commonplace and the falling
      costs of full-genome sequencing, there will be an increasingly large number of
      variants identified in research participants that may be of sufficient clinical
      relevance to share. An explicit approach to triaging and communicating these
      results has yet to be developed, and even the magnitude of the task is uncertain.
      To develop an estimate of the number of variants that might qualify for
      disclosure, we apply recently published recommendations for the return of results
      to a defined and representative set of variants and then extrapolate these
      estimates to genome scale. We find that the total number of variants meeting the
      threshold for recommended disclosure ranges from 3955-12,579 (3.79%-12.06%, 95%
      CI) in the most conservative estimate to 6998-17,189 (6.69%-16.48%, 95% CI) in an
      estimate including variants with variable disease expressivity. Additionally, if
      the growth rate from the previous 4 yr continues, we estimate that the total
      number of disease-associated variants will grow 37% over the next 4 yr.

PMID- 22147368
TI  - GAGE: A critical evaluation of genome assemblies and assembly algorithms.
AB  - New sequencing technology has dramatically altered the landscape of whole-genome
      sequencing, allowing scientists to initiate numerous projects to decode the
      genomes of previously unsequenced organisms. The lowest-cost technology can
      generate deep coverage of most species, including mammals, in just a few days.
      The sequence data generated by one of these projects consist of millions or
      billions of short DNA sequences (reads) that range from 50 to 150 nt in length.
      These sequences must then be assembled de novo before most genome analyses can
      begin. Unfortunately, genome assembly remains a very difficult problem, made more
      difficult by shorter reads and unreliable long-range linking information. In this
      study, we evaluated several of the leading de novo assembly algorithms on four
      different short-read data sets, all generated by Illumina sequencers. Our results
      describe the relative performance of the different assemblers as well as other
      significant differences in assembly difficulty that appear to be inherent in the
      genomes themselves. Three overarching conclusions are apparent: first, that data
      quality, rather than the assembler itself, has a dramatic effect on the quality
      of an assembled genome; second, that the degree of contiguity of an assembly
      varies enormously among different assemblers and different genomes; and third,
      that the correctness of an assembly also varies widely and is not well correlated
      with statistics on contiguity. To enable others to replicate our results, all of
      our data and methods are freely available, as are all assemblers used in this
      study.

PMID- 22147370
TI  - An alkoxido-tin-substituted polyoxometalate [(MeO)SnW5O18]3-: the first member of
      a new family of reactive {SnW5} Lindqvist-type anions.

PMID- 22147369
TI  - Rare versus common variants in pharmacogenetics: SLCO1B1 variation and
      methotrexate disposition.
AB  - Methotrexate is used to treat autoimmune diseases and malignancies, including
      acute lymphoblastic leukemia (ALL). Inter-individual variation in clearance of
      methotrexate results in heterogeneous systemic exposure, clinical efficacy, and
      toxicity. In a genome-wide association study of children with ALL, we identified
      SLCO1B1 as harboring multiple common polymorphisms associated with methotrexate
      clearance. The extent of influence of rare versus common variants on
      pharmacogenomic phenotypes remains largely unexplored. We tested the hypothesis
      that rare variants in SLCO1B1 could affect methotrexate clearance and compared
      the influence of common versus rare variants in addition to clinical covariates
      on clearance. From deep resequencing of SLCO1B1 exons in 699 children, we
      identified 93 SNPs, 15 of which were non-synonymous (NS). Three of these NS SNPs
      were common, with a minor allele frequency (MAF) >5%, one had low frequency (MAF
      1%-5%), and 11 were rare (MAF <1%). NS SNPs (common or rare) predicted to be
      functionally damaging were more likely to be found among patients with the lowest
      methotrexate clearance than patients with high clearance. We verified lower
      function in vitro of four SLCO1B1 haplotypes that were associated with reduced
      methotrexate clearance. In a multivariate stepwise regression analysis adjusting
      for other genetic and non-genetic covariates, SLCO1B1 variants accounted for
      10.7% of the population variability in clearance. Of that variability, common NS
      variants accounted for the majority, but rare damaging NS variants constituted
      17.8% of SLCO1B1's effects (1.9% of total variation) and had larger effect sizes
      than common NS variants. Our results show that rare variants are likely to have
      an important effect on pharmacogenetic phenotypes.

PMID- 22147371
TI  - The cover. Point Lobos.

PMID- 22147372
TI  - A piece of my mind. His patients. My patients.

PMID- 22147373
TI  - Influential groups propose less frequent cervical cancer screening for most
      women.

PMID- 22147374
TI  - Hospital palliative care programs raise grade to B in new report card on access.

PMID- 22147375
TI  - Natural language processing and electronic medical records.

PMID- 22147376
TI  - Lesbian, gay, bisexual, and transgender health and medical education.

PMID- 22147377
TI  - Changing the evaluation of future physicians.

PMID- 22147378
TI  - Aging of US presidents.

PMID- 22147380
TI  - Association of androgen deprivation therapy with cardiovascular death in patients
      with prostate cancer: a meta-analysis of randomized trials.
AB  - CONTEXT: Whether androgen deprivation therapy (ADT) causes excess cardiovascular
      deaths in men with prostate cancer is highly controversial and was the subject of
      a joint statement by multiple medical societies and a US Food and Drug
      Administration safety warning. OBJECTIVE: To perform a systematic review and meta
      analysis of randomized trials to determine whether ADT is associated with
      cardiovascular mortality, prostate cancer-specific mortality (PCSM), and all
      cause mortality in men with unfavorable-risk, nonmetastatic prostate cancer. DATA
      SOURCES: A search of MEDLINE, EMBASE, and the Cochrane Central Register of
      Controlled Trials databases for relevant randomized controlled trials in English
      between January 1, 1966, and April 11, 2011. STUDY SELECTION: Inclusion required
      nonmetastatic disease, intervention group with gonadotropin-releasing hormone
      agonist-based ADT, control group with no immediate ADT, complete information on
      cardiovascular deaths, and median follow-up of more than 1 year. DATA EXTRACTION:
      Extraction was by 2 independent reviewers. Summary incidence, relative risk (RR),
      and CIs were calculated using random-effects or fixed-effects models. RESULTS:
      Among 4141 patients from 8 randomized trials, cardiovascular death in patients
      receiving ADT vs control was not significantly different (255/2200 vs 252/1941
      events; incidence, 11.0%; 95% CI, 8.3%-14.5%; vs 11.2%; 95% CI, 8.3%-15.0%; RR,
      0.93; 95% CI, 0.79-1.10; P = .41). ADT was not associated with excess
      cardiovascular death in trials of at least 3 years (long duration) of ADT (11.5%;
      95% CI, 8.1%-16.0%; vs 11.5%; 95% CI, 7.5%-17.3%; RR, 0.91; 95% CI, 0.75-1.10; P
      = .34) or in trials of 6 months or less (short duration) of ADT (10.5%; 95% CI,
      6.3%-17.0%; vs 10.3%; 95% CI, 8.2%-13.0%; RR, 1.00; 95% CI, 0.73-1.37; P = .99).
      Among 4805 patients from 11 trials with overall death data, ADT was associated
      with lower PCSM (443/2527 vs 552/2278 events; 13.5%; 95% CI, 8.8%-20.3%; vs
      22.1%; 95% CI, 15.1%-31.1%; RR, 0.69; 95% CI, 0.56-0.84; P < .001) and lower all
      cause mortality (1140/2527 vs 1213/2278 events; 37.7%; 95% CI, 27.3%-49.4%; vs
      44.4%; 95% CI, 32.5%-57.0%; RR, 0.86; 95% CI, 0.80-0.93; P < .001). CONCLUSION:
      In a pooled analysis of randomized trials in unfavorable-risk prostate cancer,
      ADT use was not associated with an increased risk of cardiovascular death but was
      associated with a lower risk of PCSM and all-cause mortality.

PMID- 22147381
TI  - Update: A 52-year-old woman with obesity: review of bariatric surgery.

PMID- 22147382
TI  - Next-generation DNA sequencing, regulation, and the limits of paternalism: the
      next challenge.

PMID- 22147383
TI  - New HHS data standards for race, ethnicity, sex, primary language, and disability
      status.

PMID- 22147384
TI  - Androgen deprivation therapy and competing risks.

PMID- 22147386
TI  - A 23-year-old woman with a right femoral neck fracture.

PMID- 22147379
TI  - Association of antenatal corticosteroids with mortality and neurodevelopmental
      outcomes among infants born at 22 to 25 weeks' gestation.
AB  - CONTEXT: Current guidelines, initially published in 1995, recommend antenatal
      corticosteroids for mothers with preterm labor from 24 to 34 weeks' gestational
      age, but not before 24 weeks due to lack of data. However, many infants born
      before 24 weeks' gestation are provided intensive care. OBJECTIVE: To determine
      if use of antenatal corticosteroids is associated with improvement in major
      outcomes for infants born at 22 and 23 weeks' gestation. DESIGN, SETTING, AND
      PARTICIPANTS: Cohort study of data collected prospectively on inborn infants with
      a birth weight between 401 g and 1000 g (N = 10,541) born at 22 to 25 weeks'
      gestation between January 1, 1993, and December 31, 2009, at 23 academic
      perinatal centers in the United States. Certified examiners unaware of exposure
      to antenatal corticosteroids performed follow-up examinations on 4924 (86.5%) of
      the infants born between 1993 and 2008 who survived to 18 to 22 months. Logistic
      regression models generated adjusted odds ratios (AORs), controlling for maternal
      and neonatal variables. MAIN OUTCOME MEASURES: Mortality and neurodevelopmental
      impairment at 18 to 22 months' corrected age. RESULTS: Death or
      neurodevelopmental impairment at 18 to 22 months was significantly lower for
      infants who had been exposed to antenatal corticosteroids and were born at 23
      weeks' gestation (83.4% with exposure to antenatal corticosteroids vs 90.5%
      without exposure; AOR, 0.58 [95% CI, 0.42-0.80]), at 24 weeks' gestation (68.4%
      with exposure to antenatal corticosteroids vs 80.3% without exposure; AOR, 0.62
      [95% CI, 0.49-0.78]), and at 25 weeks' gestation (52.7% with exposure to
      antenatal corticosteroids vs 67.9% without exposure; AOR, 0.61 [95% CI, 0.50
      0.74]) but not in those infants born at 22 weeks' gestation (90.2% with exposure
      to antenatal corticosteroids vs 93.1% without exposure; AOR, 0.80 [95% CI, 0.29
      2.21]). If the mothers had received antenatal corticosteroids, the following
      events occurred significantly less in infants born at 23, 24, and 25 weeks'
      gestation: death by 18 to 22 months; hospital death; death, intraventricular
      hemorrhage, or periventricular leukomalacia; and death or necrotizing
      enterocolitis. For infants born at 22 weeks' gestation, the only outcome that
      occurred significantly less was death or necrotizing enterocolitis (73.5% with
      exposure to antenatal corticosteroids vs 84.5% without exposure; AOR, 0.54 [95%
      CI, 0.30-0.97]). CONCLUSION: Among infants born at 23 to 25 weeks' gestation,
      antenatal exposure to corticosteroids compared with nonexposure was associated
      with a lower rate of death or neurodevelopmental impairment at 18 to 22 months.

PMID- 22147387
TI  - JAMA patient page. Appendectomy.

PMID- 22147388
TI  - Detailed reaction paths for zeolite dealumination and desilication from density
      functional calculations.

PMID- 22147389
TI  - Novel metrics for evaluating improvement in discrimination: net reclassification
      and integrated discrimination improvement for normal variables and nested models.
AB  - Net reclassification and integrated discrimination improvements have been
      proposed as alternatives to the increase in the area under the curve for
      evaluating improvement in the performance of risk assessment algorithms
      introduced by the addition of new phenotypic or genetic markers. In this paper,
      we demonstrate that in the setting of linear discriminant analysis, under the
      assumptions of multivariate normality, all three measures can be presented as
      functions of the squared Mahalanobis distance. This relationship affords an
      interpretation of the magnitude of these measures in the familiar language of
      effect size for uncorrelated variables. Furthermore, it allows us to conclude
      that net reclassification improvement can be viewed as a universal measure of
      effect size. Our theoretical developments are illustrated with an example based
      on the Framingham Heart Study risk assessment model for high-risk men in primary
      prevention of cardiovascular disease.

PMID- 22147390
TI  - MPA: a treatment option for lymphocytic colitis and mesalamine-induced
      interstitial nephritis.

PMID- 22147391
TI  - Long-term effects of coping with extreme stress: longitudinal study of Vietnam
      era repatriated prisoners of war.
AB  - Captivity stressors and coping strategies were assessed shortly after the
      repatriation of Vietnam-era prisoners of war, and physical and mental health were
      assessed almost three decades later. Given research on coping goodness-of-fit,
      specifically the extent to which coping effects depend on situational
      controllability, we proposed that endorsement of the usefulness of avoidance
      based strategies in captivity would be predictive of better later-life health.
      Findings indicated that approach-based and avoidance-based coping both moderated
      the link between physical torture and later physical health functional status,
      whereas approach-based coping moderated the link between injuries at capture and
      later mental health. Specifically, greater endorsement of avoidance-based coping
      was associated with better long-term physical health for prisoners who
      experienced the most physical torture. Lower endorsement of approach-based coping
      was associated with better long-term mental health for prisoners who reported the
      most injuries at the time of capture.

PMID- 22147392
TI  - Involvement of the mesenteric ganglia on androstenedione, noradrenaline and
      nitrite release using a testis ex vivo system.
AB  - The autonomic nerve fibres converge to the testis along two major pathways, the
      superior spermatic nerve (SSN) and the inferior spermatic nerve (ISN). The object
      of this work was to evaluate whether the addition of noradrenaline (NA) in the
      ganglionic compartment of two ex vivo systems: superior mesenteric ganglion (SMG)
      SSN-testis, inferior mesenteric ganglion (IMG)-ISN-testis modulate
      androstenedione (A2), NA and nitrite release and to determine whether there are
      secretory differences between the right and the left testis. Each gonad with its
      respective ganglion was transferred into a cuvette with two compartments and
      incubated in a Dubnoff metabolic shaker. The testis incubation liquids were
      collected and analysed for NA by HPLC, A2 by RIA and nitrites by the Griess
      method. When NA is added to the IMG, A2 and NA release diminishes and nitrite
      increases in the left testis, while in the right gonad, A2 and NA increase and
      nitrite decreases. When NA was administered to the SMG, A2 and NA increase and
      nitrite diminishes in the left gonad, but they show opposite fluctuations in the
      right testis. These ex vivo systems appear to be excellent models for studying
      the sympathetic ganglionic control of the testis though A2, NA and nitrite
      release from the male gonad. It is evident that a better knowledge about the role
      of catecholamines and nitric oxide in the testis physiology may facilitate the
      understanding of some reproductive diseases.

PMID- 22147395
TI  - Predictive value of SYNTAX score in risk stratification of patients undergoing
      unprotected left main coronary artery angioplasty.
AB  - BACKGROUND: The SYNTAX score is a useful tool to evaluate percutaneous coronary
      intervention risk regarding the number, complexity, and location of lesions.
      Despite its proven value in the prognosis of three-vessel disease, there are few
      data about its usefulness in other selected subsets of patients. This study aimed
      to evaluate the prognostic value of the SYNTAX score in a population of patients
      who underwent unprotected left main coronary artery (ULMCA) angioplasty in our
      hospital. METHODS: This was a single-center study that included 118 patients
      (79.7% male; mean age, 66 +/- 12 years) who underwent ULMCA angioplasty between
      March 1999 and December 2008. Multivariate Cox logistic regression analysis was
      used to assess the relation of SYNTAX score to the incidence of cardiovascular
      death and major adverse cardiac events (MACE) - an endpoint comprised of
      cardiovascular death, non-fatal acute myocardial infarction, and target vessel
      revascularization. RESULTS: At 30 days, there were 5 cardiovascular deaths
      (4.2%). In the mean follow-up of 32 +/- 24 months, there were 17 cardiovascular
      deaths (14.4%) and 30 MACE (25.4%). At 30 days, SYNTAX score had no predictive
      value, but at long-term follow-up, it significantly predicted the occurrence of
      cardiovascular death (adjusted hazard ratio, 1.069; 95% CI, 1.030-1.109; P<.0001)
      and MACE (adjusted hazard ratio, 1.044; 95% CI, 1.013-1.076; P=.005), even after
      adjustment for potential confounders. Area under the curve for the occurrence of
      cardiovascular death and MACE was 0.75 (P=.0006) and 0.63 (P=.032), respectively.
      CONCLUSIONS: In this population of patients undergoing ULMCA angioplasty, SYNTAX
      score was demonstrated to be a valuable tool to predict long-term cardiovascular
      mortality.

PMID- 22147396
TI  - Predictors of clinical SYNTAX score in coronary artery disease: serum uric acid,
      smoking, and Framingham risk stratification.
AB  - BACKGROUND: High serum uric acid (SUA) has been well demonstrated to be
      associated with morbidity and mortality in the general population as well as in
      patients with coronary artery disease (CAD). Recent studies show that the
      clinical SYNTAX score (CSS) is a new tool for the risk stratification of patients
      with complex CAD. In this study, we aimed to evaluate whether SUA was associated
      with the complexity of CAD as evaluated by the CSS. METHODS: The study population
      consisted of 451 patients (69% male) who underwent coronary angiography for the
      assessment of CAD. A lesion was defined as significant if it caused a 50%
      reduction of the luminal diameter by visual estimation in vessels >=1.5 mm. CSS
      was calculated by multiplying the SYNTAX score by a modified value of age,
      creatinine, and ejection fraction (ACEF) score (age/ejection fraction +1 for each
      10 mL the creatinine clearance <60 mL/min per 1.73 m2). RESULTS: All subjects
      were divided into three groups according to CSS tertiles: CSSLOW (CSS 2-11; n =
      147), CSSMID (CSS 12-21; n = 152), and CSSHIGH (CSS 22-68; n = 152). The SUA
      level was prominently related with CSS (5.29 +/- 1.23 mg/dL, 6.92 +/- 1.23 mg/dL,
      and 8.31 +/- 1.46 mg/dL; P<.001). SUA was a significant predictor of CSS after
      adjustment for other risk factors (OR, 2.68; P<.001). CONCLUSION: SUA level was
      significantly associated with the severity and complexity of CAD evaluated by
      CSS. Further prospective clinical studies are needed to clarify the exact
      physiopathologic role of SUA in CAD.

PMID- 22147398
TI  - The SYNTAX score: usefulness, limitations, and future directions.

PMID- 22147397
TI  - The SYNTAX score predicts early mortality risk in the elderly with acute coronary
      syndrome having primary PCI.
AB  - BACKGROUND: The SYNTAX score (SXscore), an angiographic score reflecting coronary
      lesion complexity, predicts clinical outcomes in patients with left main or
      multivessel disease, and in patients with ST-segment elevation myocardial
      infarction undergoing primary PCI. The clinical SXscore (CSS) integrates the
      SXscore and clinical variables (age, ejection fraction, serum creatinine) into a
      single score. We analyzed these scores in elderly patients with acute coronary
      syndrome (ACS) undergoing primary PCI. The purpose of this analysis was not to
      decide which patients should undergo PCI, but to predict clinical outcomes in
      this population. METHODS: The SXscore was determined in a consecutive series of
      114 elderly patients (mean age, 79.6 +/- 4.1 years) undergoing primary PCI for
      ACS. Outcomes were stratified according to SXscore tertiles: SXLOW <=15 (n = 39),
      15< SXMID <23 (n = 40), and SXHIGH >=23 (n = 35). The primary endpoint was all
      cause mortality at 30 days. Secondary endpoints were nonfatal major adverse
      cardiac and cerebrovascular events (MACCE) at 30 days, and 1-year outcomes in
      patients discharged alive. RESULTS: Mortality at 30 days was higher in the SXHIGH
      group compared with the aggregate SXLOW+MID group (37.1% vs 5.1%; P<.0001), and
      in the CSSHIGH group compared with the aggregate CSSLOW+MID group (25.5% vs 1.4%;
      P=.0001). MACCE rates at 30 days were similar among SXscore tertiles. The CSS
      predicted 1-year MACCE rates (12.1% for CSSHIGH vs 3.1% for CSSLOW+MID; P=.03).
      CONCLUSIONS: The SXscore predicts 30-day mortality in elderly patients with ACS
      undergoing primary PCI. In patients discharged alive, the CSS predicts risk of
      MACCE at 1 year.

PMID- 22147399
TI  - Percutaneous closure of the patent ductus arteriosus using the Nit-Occlud PDA-R
      (reverse) device: initial experience reporting immediate and short-term results.
AB  - PURPOSE: To review the initial clinical outcomes of patent ductus arteriosus
      (PDA) closure using the new Nit-Occlud PDA-R device (NOPDA-R). MATERIALS AND
      METHODS: The NOPDA-R is a self-expandable, nitinol-made, premounted and cone
      shaped device with two distinctive features: reverse reconfiguration of the
      distal disc and a peculiar "snare-like" release mechanism. From May to December
      2010, 20 consecutive patients were included. RESULTS: Median age was 4.7 years
      (range, 6 months to 21 years) and weight was 16.4 kg (range, 6-49 kg). Mean PDA
      diameter at its narrowest point, usually the pulmonary end, was 2.92 +/- 0.61 mm
      (range, 2.1-4.5 mm), length was 7.05 +/- 1.17 mm (range, 4.7-9.2 mm) and diameter
      of the aortic ampulla was 9.52 +/- 1.62 mm (range, 6-13 mm). Pulmonary artery
      mean pressure was 20.6 +/- 4.49 mmHg (range, 14-28 mmHg) and Qp/Qs ratio was 2.0
      +/- 0.29 (range, 1.6- 2.5). Implantation success rate was 100%. The median
      cylinder diameter of the device was 6.53 +/- 1.05 mm (range, 5.5-8.5 mm) leading
      to a final selected device 124% larger (cylinder diameter) than the narrowest PDA
      diameter. Assessed by transthoracic color-Doppler echocardiography at 24 hours, 1
      month, and 3 months after implantation, complete closure was achieved in 60%,
      90%, and 95% of patients, respectively. There were no complications and all
      patients were discharged home the next day. CONCLUSION: Percutaneous PDA closure
      using the new NOPDA-R device was feasible, safe, and effective. Longer follow-up
      time and a larger number of patients are required to assess long-term
      performance.

PMID- 22147393
TI  - Sex hormone replacement in Turner syndrome.
AB  - The cardinal features of Turner syndrome (TS) are short stature, congenital
      abnormalities, infertility due to gonadal dysgenesis, with sex hormone
      insufficiency ensuing from premature ovarian failure, which is involved in lack
      of proper development of secondary sex characteristics and the frequent
      osteoporosis seen in Turner syndrome. But sex hormone insufficiency is also
      involved in the increased cardiovascular risk, state of physical fitness, insulin
      resistance, body composition, and may play a role in the increased incidence of
      autoimmunity. Severe morbidity and mortality affects females with Turner
      syndrome. Recent research emphasizes the need for proper sex hormone replacement
      therapy (HRT) during the entire lifespan of females with TS and new hypotheses
      concerning estrogen receptors, genetics and the timing of HRT offers valuable new
      information. In this review, we will discuss the effects of estrogen and androgen
      insufficiency as well as the effects of sex HRT on morbidity and mortality with
      special emphasis on evidence based research and areas needing further studies.

PMID- 22147400
TI  - Percutaneous closure of patent ductus arteriosus--current status.

PMID- 22147401
TI  - 30-day outcome after percutaneous coronary angioplasty in nonagenarians:
      feasibility and specific considerations in different clinical settings.
AB  - BACKGROUND: Nonagenarians have been systematically excluded from randomized
      trials dealing with invasive coronary strategies, resulting in a lack of evidence
      based guidelines regarding the optimal approach in this population. AIM: To
      describe the clinical and procedural characteristics and outcomes of patients 90
      years of age or older who were treated with percutaneous coronary interventions
      (PCI). METHODS: We evaluated the 30-day outcomes of patients 90 years or older
      who underwent PCI at our institution, comparing the ST-segment elevation
      myocardial infarction (STEMI) subgroup with the non-STEMI/unstable angina (UA)
      and stable angina (SA) subgroups, who had been referred for coronary angiography.
      RESULTS: Over the time period 2002-2011, we identified 45 nonagenarians (mean
      age, 93 years; range, 90-102 years). The majority (59%) presented with an acute
      coronary syndrome and underwent immediate coronary revascularization by PCI.
      Technical success rate was 90%. The frequency of in-hospital death, need for
      urgent coronary artery bypass surgery, periprocedural cerebrovascular accident,
      and major adverse cardiovascular and cerebral events was 11%, 4.5%, 4.5%, and
      18%, respectively. At 30 days, mortality was exclusively related to the STEMI
      subgroup with hemodynamic instability, compared with the non STEMI/UA and SA
      population. CONCLUSIONS: In carefully selected nonagenarians, PCI in contemporary
      practice may be performed with a high technical success rate with relatively low
      morbidity and mortality. Questions are raised about the feasibility and outcome
      of invasive coronary strategies in the high-risk clinical subgroup of STEMI and
      hemodynamic instability.

PMID- 22147402
TI  - Percutaneous coronary intervention in the very elderly: do nonagenarians have the
      most to gain or the most to lose?

PMID- 22147403
TI  - Radial artery spasm during transradial coronary procedures.
AB  - Although transradial access (TRA) for coronary procedures has many advantages
      over the transfemoral approach, it's still not the dominant route used in
      coronary interventions. Radial artery spasm (RAS) is an important limitation of
      TRA. We performed a search of published literature to estimate the prevalence and
      possible risk factors of RAS in patients undergoing transradial coronary
      procedure. Nineteen published papers including 7197 patients were identified as
      relevant; reported incidence of RAS was 14.7% altogether. It varies depending
      upon the criteria used, on applied premedications, and on sheath or catheter
      selection. Use of hydrophilic coated sheaths and catheters can reduce the
      incidence of RAS to 1%, while intra-arterial application of verapamil (1.25-5 mg)
      and nitroglycerin (100-200 MUg) can reduce the incidence of RAS up to 3.8%. We
      concluded that RAS is still problematic in transradial access, and that besides
      hydrophilic materials, the use of intra-arterial vasodilators remains mandatory
      in RAS prevention. However, the optimal spasmolytic cocktail is yet to be
      confirmed by valid spasm criteria.

PMID- 22147404
TI  - Early detection of chronic myocardial ischemia in a patient implanted with an ICD
      capable of intracardiac electrogram monitoring.
AB  - Although myocardial ischemia monitored by some implantable cardioverter
      defibrillators has the potential to improve patient care, no clinical experience
      with this novel technology has been described yet. We report for the first time
      ischemic intracardiac ST changes detected in a patient with coronary artery
      disease.

PMID- 22147405
TI  - False left ventricular apical aneurysm--a rare complication after transapical
      aortic valve replacement.
AB  - We report on a case of a false aneurysm at the access site after transapical
      aortic valve replacement. Although this is not the first case report about this
      issue, our case emphasizes the importance of follow-up echocardiography after
      transapical aortic valve replacement that focuses not only on prosthesis
      function, but also on detecting probable complications of the surgical access
      site.

PMID- 22147406
TI  - Successful coronary intervention of circumflex artery originating from an
      anomalous left main coronary artery using a novel support catheter: a case report
      and review of literature.
AB  - Anomalous coronary arteries pose a great challenge during percutaneous
      intervention due to various technical factors. Inadequate guide support leads to
      significant obstacles for delivery of interventional devices to stenotic areas.
      Several methods have been proposed to overcome these obstacles. We present a
      novel technique where we used the Guideliner support catheter (Vascular
      Solutions, Inc.) to successfully intervene on a left circumflex coronary artery
      arising from a left main coronary artery anomalously arising from the right sinus
      of Valsalva.

PMID- 22147407
TI  - Very late stent thrombosis approximately 7 years after deployment and one-week
      cessation of dual antiplatelet therapy.
AB  - This work describes the longest reported interval between drug-eluting stent
      (DES) placement and very late stent thrombosis (VLST). A 69-year-old male
      presented with substernal chest pain associated with ST-segment myocardial
      infarction (STEMI) after having a DES deployed 6.9 years (2506 days) prior. The
      patient's medical history revealed several risk factors for VLST. The patient
      suspended clopidogrel therapy in preparation for elective cystoscopy
      approximately 10 days before presenting.

PMID- 22147408
TI  - A self-expandable coronary stent system to treat complex coronary stenosis
      complicated by poststenotic aneurysm: an optical coherence tomographic evidence
      based case report.
AB  - Coronary artery aneurysm is a relatively uncommon disorder characterized by
      coronary artery dilatation with diameter that exceeds 50% of the normal adjacent
      segments with atherosclerosis being the most common etiology. Aneurysms can be
      adjacent to a stenosis in a post- or prestenotic location. Both anatomical
      conditions are technically challenging regarding their percutaneous treatment
      because of the large discrepancy in size between the stenotic and dilated
      segments, and require careful choice of the most appropriate technique and
      device. We have successfully treated a coronary stenosis complicated by a
      poststenotic aneurysm in a 60-year-old patient with atypical angina using a novel
      self-expandable coronary stent system implanted with optical coherence tomography
      (OCT) guidance. OCT scan after implantation showed residual stent malapposition
      inside the aneurysm despite postdilatation. Thanks to the ability of this stent
      to self-expand over time, 6-month OCT follow-up showed an optimal result in terms
      of stent apposition, strut coverage, and absence of in-stent restenosis.

PMID- 22147409
TI  - Distal left anterior descending coronary artery obstruction: a rare complication
      of transapical aortic valve implantation.
AB  - Apical complications are considered the "Achilles' heel" of transapical aortic
      valve implantation, in which laceration and hemorrhage are potentially fatal. We
      describe the case of a rare complication of the transapical aortic valve
      implantation procedure, where after apical closure, tension on a distal coronary
      segment resulted in flow obstruction. Clinicians should be alert to the
      possibility of distal left anterior descending artery obstruction when ischemia
      following a transapical procedure is suspected. The exact location of sheath
      insertion during "transapical" aortic valve implantation is usually apicolateral.
      A more apical insertion should be avoided since the apex is a relatively weak
      region and there could be an increased risk of coronary avulsion or apical
      ventricular septal defect. Nevertheless, a too-lateral insertion could diminish
      the sheath orientation toward the left ventricular outflow tract and the sheath
      could also be entrapped with mitral valve chordae. Surgeons should be aware of
      these factors when deciding on the exact sheath insertion site during tranaspical
      procedures.

PMID- 22147410
TI  - Atresia of the left internal mammary artery graft following percutaneous
      intervention of the left main.
AB  - Because of its durability and patency, the left internal mammary artery (LIMA) is
      preferentially used to bypass obstructive lesions in the left main coronary
      artery (LMCA) and/or the left anterior descending coronary artery (LAD). The long
      term patency of the LIMA graft is determined by several factors, principal among
      them being the dynamic competition between flow through the internal mammary
      artery graft and the LAD. We report a patient with LMCA stenosis and a well
      functioning and mature LIMA graft, who after percutaneous intervention of the
      LMCA and normalized antegrade flow in the LAD, developed atresia of a large
      caliber LIMA graft.

PMID- 22147411
TI  - The feasibility of using Ikari left catheter via the right radial approach in a
      patient with dextrocardia for better guiding support.
AB  - Dextrocardia with situs inversus is a rare cardiac anomaly, and the incidence of
      ischemic heart disease is the same as the general population. In most of these
      patients, interventionalists may encounter technical difficulties while handling
      guiding catheters and acquiring more back-up forces. We describe a case of
      successful anatomical right coronary intervention with Ikari left guiding
      catheter in a patient with situs inversus.

PMID- 22147412
TI  - Early prosthetic valve endocarditis complicating repeated attempts at CoreValve
      implantation.
AB  - Transcatheter aortic valve implantation is emerging as a promising, effective
      therapy for high-risk patients not eligible to undergo surgical aortic valve
      replacement. Infection complications have only rarely been reported. We report a
      case of probable endocarditis caused by coagulase-negative Staphylococcus
      following repeated attempts at implantation of a CoreValve bioprosthesis.

PMID- 22147413
TI  - Intrapericardial synthetic glue injection--a last resort effort to salvage
      recurrent cardiac tamponade secondary to coronary microleak post PCI.
AB  - We report a case of cardiac tamponade caused by a coronary microleak from an
      unapparent site that was successfully managed by sealing of the pericardial space
      with intrapericardial injection of sterile synthetic glue which, to the best of
      our knowledge, is the first report of its kind for post-PCI coronary leaks.

PMID- 22147414
TI  - Sorafenib inhibits neuroblastoma cell proliferation and signaling, blocks
      angiogenesis, and impairs tumor growth.
AB  - BACKGROUND: More effective therapy for children with high-risk neuroblastoma is
      desperately needed. Preclinical studies have shown that neuroblastoma tumor
      growth can be inhibited by agents that block angiogenesis. We hypothesized that
      drugs which target both neuroblastoma cells and tumor angiogenesis would have
      potent anti-tumor activity. In this study we tested the effects of sorafenib, a
      multi-kinase inhibitor, on neuroblastoma cell proliferation and signaling, and in
      mice with subcutaneous human neuroblastoma xenografts or orthotopic adrenal
      tumors. PROCEDURE: Mice with subcutaneous neuroblastoma xenografts or orthotopic
      adrenal tumors were treated with sorafenib, and tumor growth rates were measured.
      Blood vessel architecture and vascular density were evaluated histologically in
      treated and control neuroblastoma tumors. The in vitro effects of sorafenib on
      neuroblastoma proliferation, cell cycle, and signaling were also evaluated.
      RESULTS: Sorafenib inhibited tumor growth in mice with subcutaneous and
      orthotopic adrenal tumors. Decreased numbers of cycling neuroblastoma cells and
      tumor blood vessels were seen in treated versus control tumors, and the blood
      vessels in the treated tumors had more normal architecture. Sorafenib treatment
      also decreased neuroblastoma cell proliferation, attenuated ERK signaling, and
      enhanced G(1) /G(0) cell cycle arrest in vitro. CONCLUSIONS: Our results
      demonstrate that sorafenib inhibits the growth of neuroblastoma tumors by
      targeting both neuroblastoma cells and tumor blood vessels. Single agent
      sorafenib should be evaluated in future phase II neuroblastoma studies.

PMID- 22147415
TI  - Metallization of a genetically engineered polypeptide.
AB  - Recently, well-ordered biological materials have been exploited to pattern
      inorganic nanoparticles into linear arrays that are of particular interest for
      nanoelectronic applications. In this work, a de novo designed E. coli-expressed
      polypeptide (previously shown to form highly rectilinear, beta-sheet-containing
      structures) operates as a template for divalent metal cations. EDX and TEM
      analysis verify the attachment of platinum ions to the histidine-rich fibril
      surface, which was designed specifically to facilitate attachment of chemical
      moieties. Following chemical reduction, TEM further confirms the formation of
      localized zero-valent metal aggregates with sub-nanometer interparticle spacing.

PMID- 22147416
TI  - Modeling nonlinear optics of nanosystems with sum-over-states model.
AB  - Three-stage strategies (ladder rule, few state model (FSM), and parallelization)
      were proposed to improve the computational efficiency of the sum-over-states
      (SOS) model in nonlinear optics (NLO) modeling. Ladder rule decomposes NLO
      coefficients of the nth state into the (n-1)th term and the contribution from the
      (n-1)th to the nth state without loss of rigor in theory. FSM singles out the
      states with substantial contribution to NLO. Those strategies are universal to
      all (including revised and simplified) SOS models. The computing cost reduces
      roughly to C/(n(i-1)) (C is a constant and i is the rank (order) of the NLO
      coefficients).

PMID- 22147417
TI  - Forsythoside B protects against experimental sepsis by modulating inflammatory
      factors.
AB  - The present study investigated the effects of Forsythoside B on an experimental
      model of sepsis induced by caecal ligation and puncture (CLP) in rats and
      elucidated the potential mechanism in cultured RAW 264.7 cells. Results showed
      that Forsythoside B concentration-dependently down-regulated the levels of TNF
      alpha, IL-6 and high-mobility group-box 1 protein (HMGB1) in lipopolysaccharide
      (LPS)-stimulated RAW264.7 cells, inhibited the IkappaB kinase (IKK) pathway and
      modulated nuclear factor (NF)- kappaB. Intravenous injection (i.v.) of
      Forsythoside B alone or plus Imipenem reduced serum levels of TNF-alpha, IL-6,
      HMGB1, triggering receptor expressed on myeloid cells (TREM-1) and endotoxin,
      while the serum level of IL-10 was up-regulated and myeloperoxidase (MPO) in
      lung, liver and small intestine was reduced. Meanwhile, i.v. of Forsythoside B
      alone or plus Imipenem reduced CLP-induced lethality in rats. These data
      indicated that the antisepsis effect of Forsythoside B is mediated by decreasing
      local and systemic levels of a wide spectrum of inflammatory mediators. Its
      antisepsis mechanism may be that Forsythoside B binds to LPS and reduces the
      biological activity of serum LPS, and inhibits NF-kappaB activition. Our studies
      enhance the case for the use of Forsythoside B in sepsis. Forsythoside B itself
      has promise as a therapy for the treatment of sepsis in humans.

PMID- 22147418
TI  - Synthesis of the tellurium-derivatized phosphoramidites and their incorporation
      into DNA oligonucleotides.
AB  - In this unit, an efficient method for the synthesis of 2'-tellerium-modified
      phosphoramidite and its incorporation into oligonucleotide are presented. We
      choose 5'-O-DMTr-2,2'-anhydro-uridine and -thymidine nucleosides (S.1, S.2) as
      starting materials due to their easy preparation. The 5'-O-DMTr-2,2'-anhydro
      uridine and -thymidine can be converted to the corresponding 2'-tellerium
      derivatized nucleosides by treating with the telluride nucleophiles.
      Subsequently, the 2'-Te-nucleosides can be transformed into 3'-phosphoramidites,
      which are the building blocks for DNA/RNA synthesis. The DNA synthesis,
      purification, and applications of oligonucleotides containing 2'-Te-U or 2'-Te-T
      are described in the protocol.

PMID- 22147419
TI  - Synthesis of entecavir and its novel class of analogs.
AB  - Due to the slow kinetics of viral clearance and the spontaneous genetic
      variability of hepatitis B virus (HBV), antiviral therapy of chronic hepatitis B
      remains a clinical challenge. Entecavir (S.10; a 2'-deoxy carbocyclic guanosine
      analog with an exo-cyclic double bond on the 5'-position; Fig. 14.7.1) has been
      approved in the U.S. for the therapy of chronic hepatitis B. Entecavir is
      synthesized from D-ribose via a key allylic alcohol (S.3) intermediate. This
      intermediate is also utilized to synthesize entecavir-modified carbocyclic
      nucleosides S.13, S.15, S.19, and S.22.

PMID- 22147420
TI  - Preparation of DNA containing 5-hydroxymethyl-2'-deoxycytidine modification
      through phosphoramidites with TBDMS as 5-hydroxymethyl protecting group.
AB  - This unit describes procedures for preparation of two phosphoramidite building
      blocks III and IV, both containing a TBDMS as 5-CH(2)OH-protecting group.
      Phosphoramidites III and IV allow efficient incorporation of 5-hmC into DNA and a
      "one-step" deprotection procedure to cleanly remove all the protecting groups. A
      "two-step" deprotection strategy is compatible with ultramild DNA synthesis,
      which enables the synthesis of 5 hmC-containing DNA with additional
      modifications. Methods are also presented for their incorporation into
      oligonucleotides by solid-phase synthesis, subsequent deprotection, and HPLC
      analysis.

PMID- 22147421
TI  - Liquid chromatography-mass spectrometry analysis of DNA polymerase reaction
      products.
AB  - This unit describes experimental and analytical procedures for characterizing the
      efficiency and fidelity of translesion DNA synthesis across various DNA damages
      by DNA polymerases in vitro. This procedure utilizes primer extension assays
      followed by LC-MS and LC-MS/MS analysis of the extension products. Detailed
      explanations for the analysis of the LC-MS/MS data for deciphering the nucleotide
      sequences of the DNA fragments are also presented. This approach provides a
      significant improvement over conventional methods, as it allows detection of
      misincorporation, as well as frameshift products.

PMID- 22147422
TI  - ICON probes: synthesis and DNA methylation typing.
AB  - DNA methylation and demethylation significantly affect the deactivation and
      activation processes of gene expression, respectively. The determination of the
      location and frequency of DNA methylation is important for the elucidation of the
      mechanisms of cell differentiation and carcinogenesis and may be a useful and
      effective index for cancer diagnosis. We have developed an artificial DNA probe
      that induces a methylation detection reaction of a target cytosine in a long DNA
      sequence (ICON probe). This artificial DNA allows the rapid detection of a methyl
      group attached at the C5 position of the target cytosine. In addition, there is
      no nonspecific cleavage of genomic DNA in this reaction. The ICON probe also
      facilitates the quantification of methylation at the target cytosine using a
      small amount of genomic DNA sample. This unit provides a procedure for
      synthesizing bipyridine-modified adenosine phosphoramidite and preparation of
      ICON probes. Additionally, the protocol for the methylation quantification
      experiments by quantitative PCR utilizing ICON probes is also presented.

PMID- 22147423
TI  - Applications of differential scanning calorimetry for thermal stability analysis
      of proteins: qualification of DSC.
AB  - Differential scanning calorimetry (DSC) has been used to characterize protein
      thermal stability, overall conformation, and domain folding integrity by the
      biopharmaceutical industry. Recently, there have been increased requests from
      regulatory agencies for the qualification of characterization methods including
      DSC. Understanding the method precision can help determine what differences
      between samples are significant and also establish the acceptance criteria for
      comparability and other characterization studies. In this study, we identify the
      parameters for the qualification of DSC for thermal stability analysis of
      proteins. We use these parameters to assess the precision and sensitivity of DSC
      and demonstrate that DSC is suitable for protein thermal stability analysis for
      these purposes. Several molecules from different structural families were
      studied. The experiments and data analyses were performed by different analysts
      using different instruments at different sites. The results show that the
      (apparent) thermal transition midpoint (T(m)) values obtained for the same
      protein by same and different instruments and/or analysts are quite reproducible,
      and the profile similarity values obtained for the same protein from the same
      instrument are also high. DSC is an appropriate method for assessing protein
      thermal stability and conformational changes.

PMID- 22147424
TI  - Exceptionally mild reactive stripping of native ligands from nanocrystal surfaces
      by using Meerwein's salt.

PMID- 22147425
TI  - Estimating incidence rates using exact or interval-censored data with an
      application to hospital-acquired infections.
AB  - Health-care providers in the UK and elsewhere are required to maintain records of
      incidents relating to patient safety, including the date and time of each
      incident. However, for reporting and analysis, the resulting data are typically
      grouped into discrete time intervals, for example, weekly or monthly counts. The
      grouping represents a potential loss of information for estimating variations in
      incidence over time. We use a Poisson point process model to quantify this loss
      of information. We also suggest some diagnostic procedures for checking the
      goodness of fit of the Poisson model. Finally, we apply the model to the data on
      hospital-acquired methicillin-resistant Staphylococcus aureus infections in two
      hospitals in the north of England. We find that, in one of the hospitals, the
      estimated incidence decreased by a factor of approximately 2.3 over a 7-year
      period from 0.323 to 0.097 cases per day per 1000 beds, whereas in the other, the
      estimated incidence showed only a small and nonsignificant decrease over the same
      period from 0.137 to 0.131.

PMID- 22147426
TI  - Comorbidity among depression, conduct disorder, and drug use from adolescence to
      young adulthood: examining the role of violence exposures.
AB  - We assessed relations among depression, conduct disorder, and drug use from
      adolescence to young adulthood, and evaluated whether exposure to violence
      contributed to disorder co-occurrence. We used data from the Project on Human
      Development in Chicago Neighborhoods. Respondents were 12-15 years old in 1995
      1997 (N = 1,517), and were reinterviewed in 1997-2000 (n = 1,315), and 2000-2002
      (n = 1,210). We examined exposure to violence at ages 12-15 and 14-17, and
      depression, conduct disorder, and drug use at ages 14-17 and 17-20. Multivariate
      transition models revealed an association between prior conduct disorder and drug
      use, as well as a relationship between prior depression and conduct disorder.
      Adolescent exposure to violence was associated with higher odds of conduct
      disorder and drug use but not depression. Comorbid relations between conduct
      disorder and drug use were independent of prior exposure to violence. Although
      preventing adolescent exposure to violence may reduce the risk of conduct
      disorder and drug use by young adulthood, future research needs to investigate
      alternative determinants of sequential comorbidity among depression, conduct
      disorder, and drug use in adolescence and young adulthood.

PMID- 22147427
TI  - Clinical utility of anti-glycan antibodies in pediatric Crohn's disease in
      comparison with an adult cohort.
AB  - BACKGROUND: We tested a panel of serological anti-glycan antibodies including the
      novel anti-laminarin (Anti-L) and anti-chitin (Anti-C) antibodies in pediatric
      Crohn's disease (CD) patients for diagnosis of CD and association with
      complicated CD behavior. In addition, we compared this panel in pediatric CD with
      adult CD patients for possible changes in accuracy over time. METHODS: Anti-L,
      Anti-C, anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside
      (AMCA), and anti-Saccaromyces cervisiae (gASCA) antibodies were tested in serum
      samples of 131 pediatric participants (59 CD, 27 ulcerative colitis [UC], and 45
      noninflammatory bowel disease [IBD] controls) with enzyme-linked immunosorbent
      assay (ELISA). The results were compared to an adult cohort of 728 participants
      (355 CD, 129 UC, and 244 non-IBD controls). RESULTS: In all, 78% of the pediatric
      CD patients were positive for at least one of the anti-glycan antibodies. gASCA
      was most accurate for the diagnosis of CD, but combined use of the antibodies
      improved differentiation of CD from UC. gASCA, AMCA, ALCA, or Anti-L and an
      increasing antibody level were independently linked to complicated CD behavior,
      CD-related surgery, and ileal disease location (odds ratio 3.9-8.7). Considering
      the age at sample procurement the accuracy of the markers compared to an adult
      cohort remained stable for the differentiation of CD versus UC as well as for the
      association with complications, CD-related surgery, and ileal disease
      involvement. CONCLUSIONS: A panel of anti-glycan antibodies including the novel
      Anti-L and Anti-C may aid in the differentiation of pediatric CD from UC and is
      associated with complicated CD behavior. The marker accuracy remained constant
      over time.

PMID- 22147428
TI  - The promise and shortcomings of XML as an interchange format for computational
      models of biology.

PMID- 22147429
TI  - Absence of BRAF mutation in pediatric and adolescent germ cell tumors indicate
      biological differences to adult tumors.
AB  - The V600E mutation of the BRAF gene has been reported to be associated with poor
      prognosis of germ cell tumors in adult patients. We analyzed the mutational
      status of the BRAF and KRAS gene as well as MLH1 and MSH6 expression as surrogate
      markers for microsatellite instability in 70 pediatric germ cell tumors. Neither
      BRAF and KRAS mutations nor loss of MLH1 and MSH6 expression were found. Our data
      provide further evidence for patient age related biological differences in germ
      cell tumors and demonstrate that prognostic biomarkers cannot necessarily be
      transferred from one age group to the other.

PMID- 22147430
TI  - Poly(amidoamine)-based dendrimer/siRNA complexation studied by computer
      simulations: effects of pH and generation on dendrimer structure and siRNA
      binding.
AB  - In this work we report, compare and discuss the results obtained from fully
      atomistic molecular dynamics simulations of generations 4, 5, and 6 of PAMAM
      based dendrimers having NH(3)  and triethanolamine as cores, forming complexes
      with a short interfering RNA (siRNA) at different pH values and at physiological
      ionic strength. By employing a detailed analysis we demonstrate how features such
      as molecular size, structural details, and protonation level of this category of
      dendrimers affect the dendrimer/siRNA complexation. Properties like the
      conformational flexibility of the dendrimer, the effective charge distribution of
      the assembly, and the level of intra- and intermolecular hydrogen bonding between
      the two molecular entities are all found to play a significant role in the mutual
      interactions between the nucleic acid and the hyperbranched molecules. All these
      features are of key importance in the multifaceted mechanism of dendrimer/gene
      complexation, and their understanding can provide valuable insight toward the
      design of more efficient nucleic acid nanocarriers.

PMID- 22147431
TI  - Di(2-ethylhexyl) phthalate metabolites as markers for blood transfusion in doping
      control: intra-individual variability of urinary concentrations.
AB  - To indicate homologous or autologous blood transfusion in sports drug testing,
      quantification of increased urinary concentrations of di(2-ethylhexyl) phthalate
      (DEHP) metabolites presents a promising approach; however, the possible intra
      individual variation of the metabolite concentrations over time has not been well
      characterized. The aim of this study was to explore the intra-individual
      variability of urinary DEHP metabolites among seven volunteers without special
      occupational exposure to DEHP during one week (n = 253) in order to investigate
      the possibility of increased urinary concentrations of the metabolites caused by,
      for example, residential, dietary, or environmental exposure. Quantification of
      three DEHP metabolites--mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-oxohexyl)
      phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate--was accomplished after
      enzymatic hydrolysis of urinary glucuronide conjugates and direct injection using
      isotope-dilution liquid chromatography-tandem mass spectrometry. Although urinary
      concentrations of DEHP metabolites showed considerable intra-individual
      variation, no increased values were observed comparable to the concentrations
      measured in urine specimens collected after blood transfusion.

PMID- 22147432
TI  - The use of computer navigation in hip arthroplasty: literature review and
      evidence today.
AB  - Total hip replacement arthroplasty and hip resurfacing are two of the most
      successful orthopaedic operations performed worldwide. Critical to the success of
      these operations is the accurate placement of the components. Correct component
      alignment reduces mechanical wear and the risk of dislocation. Traditionally,
      correct component alignment relies on the surgeon referencing from the position
      of the patient on the table and anatomical landmarks. However, it is now known
      that this leads to a wide variability in component position. Computer navigation
      systems aim to optimise component placement. The purpose of this review is to
      describe the different types of computer navigation systems available and their
      use in both total hip arthroplasty and hip resurfacing.

PMID- 22147433
TI  - Haematopoietic  and  osteogenic  bone  marrow  stem  cells.
AB  - This article discusses the concept of a common stem cell for bone marrow stromal
      cells and haematopoietic cells. Until recently it was generally accepted that
      bone marrow contains two types of stem cells. One is the haemopoietic stem cell;
      the second one, the mesenchymal stem cell or stromal stem cell, gives rise to the
      stromal compartment of the marrow. The mesenchymal stem cells can differentiate
      into osteoblasts, chondroblasts, adipocytes, fibroblasts, and smooth muscle
      cells. Although the interplay between haemopoietic and stromal cells is well
      established, no transition of cells from the haemopoietic compartment into cells
      of the stromal compartment has been demonstrated.  Recent data, based on grafting
      of genetically-marked haemopoietic cells points to the possibility of the
      generation of adipocytes from haemopoietic stem cells. These findings support the
      hypothesis postulating a common precursor cell for both bone and bone
      marrow.There is evidence that osteoblasts can differentiate into adipocytes, and
      that mesenchymal cells derived from subcutaneous adipose tissue can differentiate
      into osteogenic cells. The possibility of transdifferentiation of adipocytes into
      osteoblasts has also been demonstrated.

PMID- 22147434
TI  - Problems and complications in VEPTR-based treatment.
AB  - AIM OF THE STUDY: Early-onset scoliosis with co-existing thoracic deformity is
      particularly difficult to treat, with early surgery usually being the only
      rational solution. Operative correction of the deformed spine and rib cage
      employs techniques enabling further growth of the structures, an example of which
      is the Vertical Expandable Prosthetic Titanium Rib (VEPTR), designed to provide
      dynamic stabilization of the spinal column and the thoracic cage. Our study aimed
      to present difficulties and complications related to VEPTR-based operative
      reduction of the spinal and thoracic deformities in the youngest child. MATERIAL
      AND METHODS: Twelve children aged 3 to 9 years (a mean age of 5.25 years)
      underwent sequential VEPTR-based surgery the Department of Paediatric
      Orthopaedics of the Medical University of Lublin. The subjects were qualified for
      the procedure on account of multiple congenital spine deformities (3 children),
      early-onset progressive neuromuscular scoliosis (4 children) and kyphosis
      secondary to a myelomeningocele (5 children). The number of procedures per child
      ranged from 4 to 10 and the follow-up was 10 months to 4 years (with a mean of
      2.5 years). Treatment failures and complications comprised rib fractures (4
      cases), perforation of the iliac ala by the ala hook (5 cases), pulmonary oedema
      (2 cases), hip joint destabilization (1 case), tissue reaction to the metal (4
      cases), breakage of the implant (2 cases). RESULTS AND CONCLUSIONS: The specific
      character of the method makes it liable to a variety of difficulties and
      complications that may sometimes affect the outcome. Both the authors' experience
      and published data prove the clinical effectiveness of VEPTR. Nevertheless, it is
      only a temporary means that cannot disturb the strategic anatomical elements of
      the spine which are to be involved in subsequent conventional operative
      procedures. An awareness of the limitations and possible difficulties connected
      with VEPTR allows for some modifications with which the technique continues to be
      the most effective sequential treatment of thoracic and spinal deformities in the
      youngest child.

PMID- 22147435
TI  - Our experience with surgical treatment of perinatal brachial plexus palsy-
      results in different types of lesions.
AB  - INTRODUCTION: Perinatal brachial plexus palsies can be divided into upper (C5
      C6), upper-middle (C5-C6-C7) and total injuries (C5-Th1). The study aimed to
      evaluate the results of surgical repair in the different types of palsies.
      MATERIAL AND METHODS: The patient population comprised 80 children who underwent
      primary repair of the brachial plexus (external neurolysis, internal neurolysis,
      direct neurorrhaphy, nerve grafts, extraanatomical intraplexus reconstruction,
      extraanatomical extraplexus reconstruction). 31 patients were additionally
      subjected to 39 tenomioplasty procedures. Widely recognised assessment scales
      were used to evaluate the outcome of surgical treatment of different types of
      palsies in 70 patients. RESULTS: Good and very good post-operative function of
      the glenohumeral and elbow joints was demonstrated in all patients with upper
      palsy. In the group of upper-middle injuries, 61.5% of patients presented good
      and very good function of the shoulder joint and 76.9% had good function of the
      elbow. In subjects with total brachial plexus palsy, good function of the
      glenohumeral was demonstrated by 51.2%, good function of the elbow by 61% and
      53.6% presented with a functionally useful hand. CONCLUSIONS: 1. While surgical
      repair may be indicated in brachial plexus injuries at all levels, it is usually
      inevitable in total and upper-middle palsies. 2. The surgical outcome depends on
      the extent of baseline damage to the brachial plexus, with the best prognosis in
      insolated upper palsies.

PMID- 22147436
TI  - Total hip arthroplasty with bone grafts for protrusio acetabuli.
AB  - BACKGROUND: This retrospective cohort study analyses the long-term outcomes of
      total hip arthroplasty (THA) in arthritis patients with various forms of
      acetabular protrusion. MATERIAL: We analyse 135 consecutive cemented total hip
      arthroplasties in 127 patients. Mean age of the patients was 55.2 years (range:
      30-72 years). The study group consisted of 119 women and 16 men who were followed
      up for a mean of 12.7 years. Mean preoperative function was poor, with a Harris
      score of 28.0 points. METHODS: Clinical evaluation utilized the Harris hip score,
      and radiographic assessment relied on the criteria of the Joint Committee of the
      Hip Society, AAOS and SICOT. RESULTS: Clinical outcomes of the study group were
      as follows: excellent in 35 (25.9%), good in 78 (57.8%), fair in 17 (12.6%), and
      poor in 5 (3.7%). The mean postoperative Harris score was 86.6 points. The
      radiographic outcomes were excellent in 47 (34.8%), good in 60 (44.5%), fair in
      18 (13.3%), and poor in 10 hips (7.4%). Loosening of both components was observed
      in 6 hips and of the acetabular component in 4 hips. Complications other than
      aseptic loosening were observed in 25 (18.5%) hips. CONCLUSIONS: Implant survival
      following THA in arthritis with acetabular protrusion depends mainly on proper
      bone stock reconstruction. 80-85% patients after THA with acetabular bone stock
      reconstruction achieved very good and good results following an average of 12
      years of follow-up. Patients with autogenic bone grafts achieved better outcomes.
      There was no substantial effect of aetiology, type of endoprosthesis, grade of
      acetabulum migration on the final outcome.

PMID- 22147437
TI  - Pathomorphism of spiral tibial fractures in computed tomography imaging.
AB  - BACKGROUND: Spiral fractures of the tibia are virtually homogeneous with regard
      to their pathomorphism. The differences that are seen concern the level of
      fracture of the fibula, and, to a lesser extent, the level of fracture of the
      tibia, the length of fracture cleft, and limb shortening following the trauma.
      While conventional radiographs provide sufficient information about the
      pathomorphism of fractures, computed tomography can be useful in demonstrating
      the spatial arrangement of bone fragments and topography of soft tissues
      surrounding the fracture site. MATERIAL AND METHODS: Multiple cross-sectional
      computed tomography views of spiral fractures of the tibia show the details of
      the alignment of bone chips at the fracture site, axis of the tibial fracture
      cleft, and topography of soft tissues that are not visible on standard
      radiographs. A model of a spiral tibial fracture reveals periosteal stretching
      with increasing spiral and longitudinal displacement. RESULTS: The cleft in
      tibial fractures has a spiral shape and its line is invariable. Every spiral
      fracture of both crural bones results in extensive damage to the periosteum and
      may damage bellies of the long flexor muscle of toes, flexor hallucis longus as
      well as the posterior tibial muscle. Computed tomography images of spiral
      fractures of the tibia show details of damage that are otherwise invisible on
      standard radiographs. Moreover, CT images provide useful information about the
      spatial location of the bone chips as well as possible threats to soft tissues
      that surround the fracture site. Every spiral fracture of the tibia is associated
      with disruption of the periosteum. CONCLUSIONS: 1. Computed tomography images of
      spiral fractures of the tibia show details of damage otherwise invisible on
      standard radiographs, 2. The sharp end of the distal tibial chip can damage the
      tibialis posterior muscle, long flexor muscles of the toes and the flexor
      hallucis longus, 3. Every spiral fracture of the tibia is associated with
      disruption of the periosteum.

PMID- 22147438
TI  - Back pain in lower and upper secondary school pupils living in urban areas of
      Poland. The case of Poznan.
AB  - BACKGROUND: To determine the lifetime prevalence and characteristics of non
      specific back pain (low back pain, upper back pain) and neck pain in adolescents
      living in urban areas of Poland. We also studied the impact of back/neck pain on
      adolescents' daily activity as well as the association of back pain with computer
      use, watching TV, physical work, and physical activity. MATERIAL AND METHODS. A
      school-based questionnaire survey of back pain and physical activity, computer
      use, watching TV and functional disorders was distributed among 1475 randomly
      selected adolescents aged 13 to 20 years attending lower and upper secondary
      schools in Poznan, Poland. RESULTS: A total of 986 (67%) teenagers reported
      having experienced one or more episodes of back/neck pain in their lives. Low
      back pain was the most common presentation. Back/neck pain symptoms appeared
      mostly between the 14th and 16th year of life. The daily activities mostly
      impaired by back/neck pain were physical activity, learning/concentration and
      lifting objects. No significant differences were found in computer use and
      physical activity between adolescents with and without a history of back/neck
      pain. Pain-free teenagers watched TV significantly longer. Boys with back/neck
      pain performed physical work more frequently than pain-free boys. CONCLUSIONS: 1.
      Compared to adolescents and adults in other European countries, the lifetime
      prevalence of back/neck pain in Polish adolescents living in urban areas is
      similar. 2. The findings support the hypothesis that physical activity, computer
      use and watching TV cannot be regarded as risk factors for back/neck pain. 3.
      Back/neck pain may have a negative influence on the daily activities of
      adolescents. Nevertheless, this impact is probably temporary and adolescents seem
      to develop strategies for coping with pain in order to participate normally in
      daily activities. More detailed studies of these coping strategies are
      recommended.

PMID- 22147439
TI  - Delayed diagnosis of primary hyperparathyroidism in a patient with osteoclastoma.
AB  - Primary hyperparathyroidism (HPTo) nowadays is most often recognized incidentally
      in the asymptomatic period as a result of biochemical screening or evaluation of
      low bone mass. Classical manifestations of the disease are present in about 15
      20% of patients.   We present the case of a 28-year-old male patient who had been
      treated for two years for osteoclastoma of the proximal tibia, first by
      intralesional curettage with cement filling followed by bone grafting, and
      finally with a reconstructive arthroplasty of the knee joint. The patient had
      been consulted in different medical centers by at least 14 doctors representing 9
      different specialties, but the correct diagnosis of HPTo had not been made,
      although classic  manifestations of the disease had been present for 5-6 years.
      This suggests that a diagnosis of HPTo  is difficult nowadays. Therefore,
      determination of serum calcium concentration and other markers of calcium and
      phosphate metabolism should be obligatory in patients with bone lesions.

PMID- 22147440
TI  - Dislocation of the patella in a patient with Rubinstein-Taybi syndrome--a case
      study.
AB  - The Rubinstein-Taybi syndrome is a rare syndrome of congenital disorders whose
      etiology is still unknown. Most RTS patients have musculoskeletal abnormalities
      which, if untreated, may significantly affect independent mobility.   This paper
      presents the results of a surgical treatment of a 13-year-old patient with RTS
      and instability of the patellofemoral joint. The patient was followed up for 3
      years. Surgery resulted in complete pain relief, increased knee range of motion
      and marked improvement in the patient's gait.    An extensive plasty of the
      extensor apparatus of the knee joint increases the likelihood of a good and
      lasting treatment result in patients with RTS and instability of the
      patellofemoral joint.

PMID- 22147441
TI  - Effects of maple (Acer) plant part extracts on proliferation, apoptosis and cell
      cycle arrest of human tumorigenic and non-tumorigenic colon cells.
AB  - Phenolic-enriched extracts of maple sap and syrup, obtained from the sugar and
      red maple species (Acer saccharum Marsh, A. rubrum L., respectively), are
      reported to show anticancer effects. Despite traditional medicinal uses of
      various other parts of these plants by Native Americans, they have not been
      investigated for anticancer activity. Here leaves, stems/twigs, barks and
      sapwoods of both maple species were evaluated for antiproliferative effects
      against human colon tumorigenic (HCT-116, HT-29, Caco-2) and non-tumorigenic (CCD
      18Co) cells. Extracts were standardized to total phenolic and ginnalin-A
      (isolated in our laboratory) levels. Overall, the extracts inhibited the growth
      of the colon cancer more than normal cells (over two-fold), their activities
      increased with their ginnalin-A levels, with red > sugar maple extracts. The red
      maple leaf extract, which contained the highest ginnalin-A content, was the most
      active extract (IC50  = 35 and 16 ug/mL for extract and ginnalin-A,
      respectively). The extracts were not cytotoxic nor did they induce apoptosis of
      the colon cancer cells. However, cell cycle analyses revealed that the
      antiproliferative effects of the extracts were mediated through cell cycle arrest
      in the S-phase. The results from the current study suggest that these maple plant
      part extracts may have potential anticolon cancer effects.

PMID- 22147442
TI  - Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory
      cell line and in zebrafish.
AB  - Cisplatin is a very effective anticancer drug and generates reactive oxygen
      species (ROS) such as superoxide anions that can deplete antioxidant protective
      molecules in the cochlea. These processes result in the death of cochlear hair
      cells by induction of apoptosis. Apocynin, which is used as a specific
      nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive
      effect for intracellular ROS generation. In this study, the effect of apocynin
      was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 cells,
      and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects
      of apocynin, HEI-OC1 cells were treated with various concentrations of apocynin
      and a 20 um concentration of cisplatin, simultaneously. An in vivo study of
      transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects
      of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin
      appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258
      staining in the HEI-OC1 cells. Treatment of the HEI-OC1 cells with 100 um of
      apocynin, significantly decreased caspase-3 activity. Treatment of the cells with
      a 100 um concentration of apocynin and a 20 um concentration of cisplatin
      significantly decreased the intracellular ROS production. In the in vivo study,
      apocynin significantly decreased the TUNEL reaction and prevented cisplatin
      induced hair cell loss of the neuromasts in the transgenic zebrafish at low
      concentrations (125 and 250 um). These findings suggest that apocynin has
      antioxidative effects and prevents cisplatin-induced apoptotic cell death in HEI
      OC1 cells as well as in zebrafish.

PMID- 22147443
TI  - Activated methane on small cationic platinum clusters.

PMID- 22147444
TI  - A randomized controlled trial of rituximab following failure of antiviral therapy
      for hepatitis C virus-associated cryoglobulinemic vasculitis.
AB  - OBJECTIVE: To perform a randomized controlled trial of rituximab in patients with
      hepatitis C virus (HCV)-associated mixed cryoglobulinemic vasculitis. METHODS: We
      conducted a single-center, open-label, randomized controlled trial of rituximab
      (375 mg/ m(2) /week for 4 weeks) compared to the best available therapy
      (maintenance or increase in immunosuppressive therapy) for HCV-associated
      cryoglobulinemic vasculitis in patients in whom antiviral therapy had failed to
      induce remission. The primary end point was disease remission at 6 months from
      study entry. RESULTS: A total of 24 patients were enrolled (12 in each treatment
      group). Baseline disease activity and organ involvement were similar in the two
      groups. Ten patients in the rituximab group (83%) were in remission at study
      month 6, as compared with 1 patient in the control group (8%), a result that met
      the criterion for stopping the study (P < 0.001). The median duration of
      remission for rituximab-treated patients who reached the primary end point was 7
      months. No adverse effects of rituximab on HCV plasma viremia or on hepatic
      transaminase levels were observed. CONCLUSION: Rituximab was a well-tolerated and
      effective treatment in patients with HCV-associated cryoglobulinemic vasculitis
      in whom antiviral therapy failed to induce remission.

PMID- 22147445
TI  - Functional consequences of genetic variations in the human organic anion
      transporting polypeptide 1B3 (OATP1B3) in the Korean population.
AB  - The objectives of this study were to investigate the allele frequencies and
      linkage disequilibrium (LD) in the organic anion transporting polypeptide 1B3
      (OATP1B3) in the Korean population and to examine the functional consequences.
      Using samples from 48 Koreans, direct sequencing was carried out to determine the
      allele frequencies and LD of OATP1B3 in a representative Korean population.
      Thirty-six genetic variations in the transporter were found in Koreans; among
      them, five undocumented variations (i.e.,-6436G>C in the 5'-upstream region,
      26A>C and 586A>G in the protein coding region, and IVS6-72A>T and IVS12-80A>T in
      intron regions) were identified. In the upstream region, -5035G>A was found to
      have lowered gene expression, as determined by a reporter gene assay, suggesting
      that this variation reduces the expression of OATP1B3 in humans. The functional
      relevance of the genetic variations in the protein coding region was determined
      by an uptake study involving representative substrates in human embryonic kidney
      293 cells expressing wild type or variant forms. Variations involving 699G>A
      showed a reduced uptake activity for testosterone, but not for estradiol 17beta-d
      glucuronide or methotrexate, indicating that the functional impact of the
      variations is substrate specific. Considering the kinetic relevance of OATP1B3,
      the functionally affected variations may be therapeutically important.

PMID- 22147446
TI  - A Bayesian order-restricted model for hormonal dynamics during menstrual cycles
      of healthy women.
AB  - We propose a Bayesian framework for analyzing multivariate linear mixed effect
      models with linear constraints on the fixed effect parameters. The procedure can
      incorporate both firm and soft restrictions on the parameters and Bayesian model
      selection for the random effects. The framework is used to analyze data from the
      BioCycle study. One of the main objectives of the BioCycle study is to
      investigate the association between markers of oxidative stress and hormone
      levels during menstrual cycles of healthy women. Contrary to the popular belief
      that ovarian hormones are negatively associated with level of F (2) 
      isoprostanes, a known marker for oxidative stress, our analysis finds a positive
      association between ovarian hormone levels and isoprostane levels. The positive
      association corroborates the findings from a previous analysis of the BioCycle
      data.

PMID- 22147447
TI  - Combination of irinotecan and 5-fluorouracil with radiation in locally advanced
      rectal adenocarcinoma.
AB  - OBJECTIVE: To evaluate toxicity and efficacy of addition of weekly irinotecan to
      a regimen of chemoradiotherapy of 5-fluorouracil with concurrent pelvic radiation
      in patients with locally advanced rectal cancer. PATIENTS AND METHODS: Between
      October 2006 and December 2009, 36 patients with non-metastatic rectal
      adenocarcinoma were treated with chemoradiotherapy of irinotecan (50 mg/m(2)
      weekly), 5-fluorouracil (250 mg/m(2) for 5 days/week) and pelvic radiation (45
      Gy/1.8 Gy/fraction for 5 days/week) by 3D conformal radiotherapy. RESULTS: All
      patients completed the planned treatment. After the chemoradiotherapy, overall
      clinical response rate was 55.5% and pathological complete was 16.7%. Neutropenia
      was the most common hematologic toxicity (58.3%) with grade III in 5.5% while
      among non hematologic toxicity, diarrhea was the most common reported one (63.9%)
      with grade III in 13.9% followed by nausea and vomiting (47.2%). After a median
      follow-up of 23 months, progression-free and overall survival estimates at 2
      years were 72% and 91.7%, respectively. Distant relapses were recoded in 16.7%,
      the main distant failure sites were lung and liver, and local relapse was found
      in 5.6%. CONCLUSION: Combined chemoradiotherapy of irinotecan, 5-fluorouracil and
      radiotherapy for locally advanced non metastatic rectal adenocarcinoma is
      effective and safe. A prospective, randomized trial is needed to confirm these
      results in larger numbers and to compare this regimen with other non-irinotecan
      based chemoradiotherapy regimens.

PMID- 22147448
TI  - Renal Cell Carcinoma with Gastric Metastases.

PMID- 22147449
TI  - Treatment of complex PTSD: results of the ISTSS expert clinician survey on best
      practices.
AB  - This study provides a summary of the results of an expert opinion survey
      initiated by the International Society for Traumatic Stress Studies Complex
      Trauma Task Force regarding best practices for the treatment of complex
      posttraumatic stress disorder (PTSD). Ratings from a mail-in survey from 25
      complex PTSD experts and 25 classic PTSD experts regarding the most appropriate
      treatment approaches and interventions for complex PTSD were examined for areas
      of consensus and disagreement. Experts agreed on several aspects of treatment,
      with 84% endorsing a phase-based or sequenced therapy as the most appropriate
      treatment approach with interventions tailored to specific symptom sets. First
      line interventions matched to specific symptoms included emotion regulation
      strategies, narration of trauma memory, cognitive restructuring, anxiety and
      stress management, and interpersonal skills. Meditation and mindfulness
      interventions were frequently identified as an effective second-line approach for
      emotional, attentional, and behavioral (e.g., aggression) disturbances. Agreement
      was not obtained on either the expected course of improvement or on duration of
      treatment. The survey results provide a strong rationale for conducting research
      focusing on the relative merits of traditional trauma-focused therapies and
      sequenced multicomponent approaches applied to different patient populations with
      a range of symptom profiles. Sustained symptom monitoring during the course of
      treatment and during extended follow-up would advance knowledge about both the
      speed and durability of treatment effects.

PMID- 22147450
TI  - [Functional connectivity analysis of the brain network using resting-state FMRI].
AB  - Spatial patterns of spontaneous fluctuations in blood oxygenation level-dependent
      (BOLD) signals reflect the underlying neural architecture. The study of the brain
      network based on these self-organized patterns is termed resting-state functional
      MRI (fMRI). This review article aims at briefly reviewing a basic concept of this
      technology and discussing its implications for neuropsychological studies. First,
      the technical aspects of resting-state fMRI, including signal sources,
      physiological artifacts, image acquisition, and analytical methods such as seed
      based correlation analysis and independent component analysis, are explained,
      followed by a discussion on the major resting-state networks, including the
      default mode network. In addition, the structure-function correlation studied
      using diffuse tensor imaging and resting-state fMRI is briefly discussed. Second,
      I have discussed the reservations and potential pitfalls of 2 major imaging
      methods: voxel-based lesion-symptom mapping and task fMRI. Problems encountered
      with voxel-based lesion-symptom mapping can be overcome by using resting-state
      fMRI and evaluating undamaged brain networks in patients. Regarding task fMRI in
      patients, I have also emphasized the importance of evaluating the baseline brain
      activity because the amplitude of activation in BOLD fMRI is hard to interpret as
      the same baseline cannot be assumed for both patient and normal groups.

PMID- 22147451
TI  - [Quantitative white matter analysis by diffusion tensor imaging and potential
      functional correlation].
AB  - Diffusion tensor imaging (DTI) is an MRI modality used to measure the thermal
      motion of water molecules by combining the measured water diffusion with a simple
      tensor model of a 3 * 3 symmetric matrix. Since there are many structures that
      restrict the free motion of water molecules in the brain, we can use the
      diffusion property of water to study the brain anatomy. Because DTI can provide
      directional information about axonal fiber bundles, this technique may be one of
      the most effective MR tools for the investigation of the human white matter
      anatomy in vivo. Along with the qualitative analysis of fiber pathways using
      tractography, the quantitative analysis using DTI enables researchers to
      investigate relationships between white matter anatomy and brain functions as
      well as to identify tract-specific developmental patterns or disease-specific
      alterations of the fiber tracts. Several methods have been proposed for whole
      brain DTI analysis without an a priori hypothesis. Voxel-based analysis (VBA) is
      one of the most widely used approaches, although it has concerning limitations,
      especially when isotropic spatial smoothing is applied. Alternative methods such
      as tract-based spatial statistics and atlas-based analysis have been introduced
      to overcome the limitations of VBA. Future studies combining the anatomical
      connectivity illustrated by using DTI and the functional connectivity illustrated
      by using resting-state fMRI will provide an emerging landscape of human brain
      connectivity.

PMID- 22147452
TI  - [Decoding subjective mental states from FMRI activity patterns].
AB  - In recent years, functional magnetic resonance imaging (fMRI) decoding has
      emerged as a powerful tool to read out detailed stimulus features from multi
      voxel brain activity patterns. Moreover, the method has been extended to perform
      a primitive form of 'mind-reading,' by applying a decoder "objectively" trained
      using stimulus features to more "subjective" conditions. In this paper, we first
      introduce basic procedures for fMRI decoding based on machine learning
      techniques. Second, we discuss the source of information used for decoding, in
      particular, the possibility of extracting information from subvoxel neural
      structures. We next introduce two experimental designs for decoding subjective
      mental states: the "objective-to-subjective design" and the "subjective-to
      subjective design." Then, we illustrate recent studies on the decoding of a
      variety of mental states, such as, attention, awareness, decision making, memory,
      and mental imagery. Finally, we discuss the challenges and new directions of fMRI
      decoding.

PMID- 22147453
TI  - [Localization of language function in the brain].
AB  - Since the first report of an aphasic patient by Paul Broca, the localization of
      brain function has been disputed for 150 years. In lesion studies, double
      dissociation has been a key concept to show the localization of particular
      cognitive functions. The advancement of non-invasive brain imaging methods
      enables us to investigate the brain activities under well-controlled conditions,
      further promoting the studies on the localization of the cognitive functions,
      including language function. Brain imaging studies, together with subtraction and
      correlation analyses, have accumulated evidence that syntax, phonology, and
      sentence comprehension are separately processed by modules in different cortical
      regions. More specifically, it has been clarified that the module for syntax
      localizes in the left lateral premotor cortex and the opercular/triangular parts
      of the left inferior frontal gyrus. This modular structure further suggests that
      aphasia is interpreted as deficits in either syntactic or phonological
      processing. Therefore, the classical model of contrasting speech production and
      comprehension should be updated. According to theoretical linguistics, on the
      other hand, the recursive computation of syntactic structures is an essential
      feature of human language faculty. One direction of research would be to contrast
      human beings and animals for the abilities of processing symbolic sequences.
      Another direction is to clarify that the human brain is indeed specialized in
      language processing, which can be revealed by well-controlled language tasks and
      functional imaging techniques. Here we will review recent studies that
      demonstrate the existence of grammar center in the left frontal cortex. The
      future studies in the neuroscience of language will eventually elucidate the
      cortical localization of language function in a more precise way, i.e., what is
      really computed in the human brain.

PMID- 22147454
TI  - [Frontal lobes and inhibitory function].
AB  - Neuropsychological studies using traditional tasks of inhibitory functions, such
      as the Wisconsin card sorting test (WCST) and the Go/No-Go Task have revealed
      that the frontal lobe is responsible for several types of inhibitory functions.
      However, the detailed psychological nature of the inhibitory functions and the
      precise location of their critical foci within the frontal lobe remain to be
      investigated. Functional magnetic resonance imaging provides spatial and temporal
      resolution that allowed us to illuminate at least 4 frontal regions involved in
      inhibitory functions: the dorsolateral, ventrolateral, and rostral parts of the
      frontal lobe and the presupplementary motor area (preSMA). The ventrolateral part
      of the frontal lobe in the right hemisphere was activated during response
      inhibition. The preSMA in the left hemisphere was activated during inhibition of
      proactive interference immediately after the dimension changes of the WCST. The
      rostral part of the frontal lobe in the left hemisphere was activated during
      inhibition long after the dimension changes. The dorsolateral part of the frontal
      lobe in the left hemisphere was activated at the dimension changes in the first
      time, but not in the second time. These findings provide clues to our
      understanding of functional differentiation of inhibitory functions and their
      localization in the frontal lobe.

PMID- 22147455
TI  - [Neural and cognitive correlates of social cognition: findings on
      neuropsychological and neuroimaging studies].
AB  - Social cognition includes various components of information processing related to
      communication with other individuals. In this review, we have discussed 3
      components of social cognitive function: face recognition, empathy, and decision
      making. Our social behavior involves recognition based on facial features and
      also involves empathizing with others; while making decisions, it is important to
      consider the social consequences of the course of action followed. Face
      recognition is divided into 2 routes for information processing: a route
      responsible for overt recognition of the face's identity and a route for
      emotional and orienting responses based on the face's personal affective
      significance. Two systems are possibly involved in empathy: a basic emotional
      contagion "mirroring" system and a more advanced "theory of mind" system that
      considers the cognitive perspective. Decision making is mediated by a widespread
      system that includes several cortical and subcortical components. Numerous lesion
      and neuroimaging studies have contributed to clarifying the neural correlates of
      social cognitive function, and greater information can be obtained on social
      cognitive function by combining these 2 approaches.

PMID- 22147456
TI  - [Music therapy for dementia and higher cognitive dysfunction: a review].
AB  - Music is known to affect the human mind and body. Music therapy utilizes the
      effects of music for medical purposes. The history of music therapy is quite
      long, but only limited evidence supports its usefulness in the treatment of
      higher cognitive dysfunction. As for dementia, some studies conclude that music
      therapy is effective for preventing cognitive deterioration and the occurrence of
      behavioral and psychological symptoms of dementia (BPSD). In patients receiving
      music therapy for the treatment of higher cognitive dysfunction, aphasia was
      reported as the most common symptom. Many studies have been conducted to
      determine whether singing can improve aphasic symptoms: singing familiar and/or
      unfamiliar songs did not show any positive effect on aphasia. Melodic intonation
      therapy (MIT) is a method that utilizes melody and rhythm to improve speech
      output. MIT is a method that is known to have positive effects on aphasic
      patients. Some studies of music therapy for patients with unilateral spatial
      neglect; apraxia; hemiparesis; and walking disturbances, including parkinsonian
      gait, are available in the literature. Studies showed that the symptoms of
      unilateral spatial neglect and hemiparesis significantly improved when musical
      instruments were played for several months as a part of the music therapy. Here,
      I describe my study in which mental singing showed a positive effect on
      parkinsonian gait. Music is interesting, and every patient can go through
      training without any pain. Future studies need to be conducted to establish
      evidence of the positive effects of music therapy on neurological and
      neuropsychological symptoms.

PMID- 22147457
TI  - [IDH1/2 mutations in gliomas].
AB  - The NADP+-dependent isocitrate dehydrogenases 1 and 2 (IDH1/2) catalyze the
      oxidative decarboxylation of isocitrate into alpha-ketoglutarate (alpha-KG). IDH1
      and IDH2 mutations have been frequently found in some types of gliomas (low-grade
      diffuse gliomas WHO grade II, anaplastic gliomas WHO grade III, and secondary
      glioblastomas WHO grade IV), and have received significant attention because of
      their specificity to single codons. Since the unveiling of IDH1/2 mutations, many
      studies have investigated their clinical impact on gliomas. While the favorable
      influence of these mutations in high-grade gliomas has been well established,
      their prognostic impact on low-grade diffuse gliomas is much less clear. While
      the mechanism of IDH1/2 mutations in gliomagenesis remains to be clarified, its
      elucidation might lead to novel therapeutic strategies against gliomas.

PMID- 22147459
TI  - Antiangiogenic metronomic therapy for children with recurrent embryonal brain
      tumors.
AB  - BACKGROUND: Median survival time of recurrent embryonal brain tumors is short
      regardless of salvage chemotherapy used. An evolving alternative approach to
      conventional chemotherapy is to target neovascularization by interfering with
      tumor angiogenesis at various levels. PROCEDURE: From November 2006 to December
      2010, 16 patients (median age: 9 years) with recurrent (9 first, 7 multiple)
      embryonal brain tumors were treated with an antiangiogenic multidrug combination
      regimen (bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide, and
      cyclophophamide) and additional intraventricular therapy (etoposide and liposomal
      cytarabine). RESULTS: At a median of 33 months, 10/16 patients are alive. 4/4
      patients with CNS primitive neuroectodermal tumors (CNS PNET) and 1/7 patients
      with medulloblastoma (MB) died of tumor progression during the first year.
      Another patient with MB died of an accident after 23 months, the remaining five
      patients with MB are alive for 12, 33, 33, 37, and 58 months. For the seven
      patients with MB, both overall survival (OS) and event free survival (EFS) after
      6 months was 100%, after 12 months 85.7 +/- 13%, and after 24 months 68.6 +/-
      19%. In contrast, for patients with CNS PNET, both OS and EFS after 6 months was
      75.0 +/- 22% and 0.0% and all patients had died by 12 months. Low-dose oral
      etoposide and cyclophosphamide was reduced after a median of 2 months and
      discontinued after a median of 11 months. Toxicities were manageable and therapy
      was generally well tolerated. CONCLUSION: Our results suggest that the chosen
      antiangiogenic drug combination is particularly beneficial for patients with MB
      and warrants further investigation.

PMID- 22147458
TI  - Comprehensive 2-dimensional gas chromatography fast quadrupole mass spectrometry
      (GC * GC-qMS) for urinary steroid profiling: mass spectral characteristics with
      chemical ionization.
AB  - Comprehensive 2-dimensional gas chromatography (GC * GC), coupled to either a
      time of flight mass spectrometry (TOF-MS) or a fast scanning quadrupole MS (qMS)
      has greatly increased the peak capacity and separation space compared to
      conventional GC-MS. However, commercial GC * GC-TOFMS systems are not equipped
      with chemical ionization (CI) and do not provide dominant molecular ions or
      enable single ion monitoring for maximal sensitivity. A GC * GC-qMS in mass
      scanning mode was investigated with electron ionization (EI) and positive CI
      (PCI), using CH(4) and NH(3) as reagent gases. Compared to EI, PCI-NH(3) produced
      more abundant molecular ions and high mass, structure-specific ions for steroid
      acetates. Chromatography in two dimensions was optimized with a mixture of 12
      endogenous and 3 standard acetylated steroids (SM15-AC) relevant to doping
      control. Eleven endogenous target steroid acetates were identified in normal
      urine based on their two retention times, and EI and PCI-NH(3) mass spectra; nine
      of these endogenous target steroid acetates were identified in congenital adrenal
      hyperplasia (CAH) patients. The difference between the urinary steroids profiles
      of normal individuals and those from CAH patients can easily be visually
      distinguished by their GC * GC-qMS chromatograms. We focus here on the comparison
      and interpretation of the various mass spectra of the targeted endogenous
      steroids. PCI-NH(3) mass spectra were most useful for unambiguous molecular
      weight determination and for establishing the number of -OH by the losses of one
      or more acetate groups. We conclude that PCI-NH(3) with GC * GC-qMS provides
      improved peak capacity and pseudomolecular ions with structural specificity.

PMID- 22147460
TI  - Vedolizumab for the treatment of active ulcerative colitis: a randomized
      controlled phase 2 dose-ranging study.
AB  - BACKGROUND: Vedolizumab is a gut-selective biologic that has shown efficacy in
      ulcerative colitis (UC) and Crohn's disease (CD). We studied the
      pharmacokinetics, pharmacodynamics, safety, tolerability, and efficacy of a new
      formulation of vedolizumab produced by an improved manufacturing process.
      METHODS: UC patients were randomized to receive vedolizumab (2, 6, or 10 mg/kg)
      or placebo on days 1, 15, 29, and 85. Safety, pharmacokinetics, pharmacodynamics,
      and immunogenicity evaluations were performed at multiple timepoints through day
      253. Partial Mayo Scores and fecal calprotectin levels were used to assess
      efficacy. RESULTS: In all, 46 patients (9 placebo, 37 vedolizumab) received at
      least one dose of study medication. The vedolizumab serum concentration declined
      monoexponentially until concentrations reached 1-10 MUg/mL, and then fell
      nonlinearly. Vedolizumab maximum serum concentration (C(max) ) and area under the
      curve (AUC) increased approximately proportionally as a function of dose.
      Vedolizumab maximally saturated alpha(4) beta(7) receptors on peripheral serum
      lymphocytes at all measurable serum concentrations. Vedolizumab was well
      tolerated, with no deaths and no adverse events leading to discontinuation. At
      every assessment from day 29 through day 253, over 50% of vedolizumab-treated
      patients were in clinical response, while placebo response rates generally ranged
      between 22% and 33%. Vedolizumab treatment reduced fecal calprotectin levels
      compared with placebo. CONCLUSIONS: Vedolizumab demonstrated dose-proportional
      pharmacokinetics and maximally saturated alpha(4) beta(7) receptors over the
      tested dose range. Multiple dosing up to 10 mg/kg was well tolerated. Over the
      course of follow-up a greater proportion of patients treated with vedolizumab
      were in clinical response than those who were assigned to placebo.

PMID- 22147461
TI  - Thermally modulated retention of lymphoctytes on polymer-brush-grafted glass
      beads.
AB  - Thermoresponsive PIPAAm-brush-grafted glass beads are prepared through siATRP and
      their physicochemical properties are characterized by micro-nitrogen analysis,
      XPS, and contact angle measurements. The amount of grafted PIPAAm on glass bead
      surfaces can be controlled by varying the ATRP reaction time, leading to a
      modulation of the temperature-dependent wettability of the prepared surfaces. To
      evaluate a possible use of the beads as cell separation matrices, loading with
      rat lymphocytes from mesenteric lymph nodes is studied. The results show that the
      interaction between PIPAAm brushes and lymphocytes can be controlled by
      modulating PIPAAm brush length and temperature. The PIPAAm-brush-grafted beads
      might therefore be useful as effective cell separation matrices.

PMID- 22147463
TI  - Autophagy modulates osteoarthritis-related gene expression in human chondrocytes.
AB  - OBJECTIVE: Autophagy, an evolutionarily conserved process for the bulk
      degradation of cytoplasmic components, serves as a cell survival mechanism. The
      purpose of this study was to elucidate the role of autophagy in human
      chondrocytes and pathophysiology of osteoarthritis (OA). METHODS: Autophagy in
      articular cartilage and primary chondrocytes was assessed using antibodies for
      the autophagy markers light chain 3 and beclin 1. The states of autophagy under
      catabolic and nutritional stresses were examined. We also examined the effects of
      inhibition or induction of autophagy under stimulation with interleukin-1beta.
      Autophagy was inhibited by small interfering RNA targeting ATG5, and autophagy
      was induced by rapamycin. The effects of inhibition or induction of autophagy
      were examined by real-time polymerase chain reaction for aggrecan, COL2A1, MMP13,
      and ADAMTS5 messenger RNA. To further examine the mechanism of autophagy
      regulation in OA human chondrocytes, we investigated whether autophagy modulates
      apoptosis and reactive oxygen species (ROS). RESULTS: Autophagy was increased in
      OA chondrocytes and cartilage. Catabolic and nutritional stresses increased
      autophagy. In addition, the inhibition of autophagy caused OA-like gene
      expression changes, while the induction of autophagy prevented them. Furthermore,
      the inhibition of autophagy increased the amount of cleaved poly(ADP-ribose)
      polymerase and cleaved caspase 9, while the induction of autophagy inhibited
      these increases. ROS activity was also decreased by induction of autophagy.
      CONCLUSION: These observations suggested that increased autophagy is an adaptive
      response to protect cells from stresses, and that autophagy regulates OA-like
      gene expression changes through the modulation of apoptosis and ROS. Further
      studies about autophagy in chondrocytes will provide novel insights into the
      pathophysiology of OA.

PMID- 22147464
TI  - Benzo[1,2-b:4,5-b']dithiophene building block for the synthesis of semiconducting
      polymers.
AB  - This review covers the synthesis and polymerization of benzo[1,2-b: 4,5
      b']dithiophene (BDT) to generate semiconducting polymers used in organic field
      effect transistors (OFET) and organic solar cells applications.

PMID- 22147465
TI  - Homology of the internal sac components in the leaf beetle subfamily Criocerinae
      and evolutionary novelties related to the extremely elongated flagellum.
AB  - Extremely elongated intromittent organs are found in a wide range of taxa,
      especially among insects. This phenomenon is generally thought to result from
      sexual selection, but it is predicted that limited storage space in the body
      cavity and the difficulty of using the elongated organs should have constrained
      the evolution of extreme elongation, neutralizing any selective advantage.
      Therefore, in groups with long intromittent organs, features that overcome these
      constraints may have evolved or coevolved together with intromittent organ
      elongation. Using a comparative morphological approach and outgroup comparisons,
      we identified potential constraints and key novelties that may neutralize such
      constraints in the leaf beetle subfamily Criocerinae. Observations of the
      internal sac structure throughout Criocerinae were performed. Comparing the
      results with preceding studies from outgroups, a ground plan of the criocerine
      internal sac was constructed. Our analysis also identified specific features that
      are always correlated with extreme elongation: the rotation of whole internal-sac
      sclerites and the possession of a pocket in which to store the elongated
      flagellum. The pocket is thought to be formed by the rotation of the sclerites,
      markedly altering internal sac shape from the criocerine ground plan. Onlythe
      clades that have acquired this derived state contain species with an elongated
      flagellum that distinctly exceeds the median lobe length. It is presumed that
      these character correlations evolved independently three times. The detected
      character correlations corroborate the hypothesis that there are latent adaptive
      constraints for the evolution of extremely elongated intromittent organs. The
      constraints may have been neutralized by the alteration from the criocerine
      ground plan resulting in the formation of a storage pocket. In conclusion,
      deviation from the criocerine ground plan is considered to be the evolutionary
      innovation that neutralized the latent adaptive constraints of flagellum
      elongation in the subfamily Criocerinae.

PMID- 22147466
TI  - Effects of increasing dried distillers grains with solubles on performance,
      carcass characteristics, and digestibility of feedlot lambs.
AB  - The objectives of this study were to determine the effects of 0, 20, 40, or 60%
      dietary dried distillers grains with solubles (DDGS) on 1) growing lamb
      performance, carcass characteristics, and tissue minerals, and 2) nutrient
      digestibility and retention in growing lambs. In Exp. 1, ninety-six lambs were
      blocked by sex (ewes, n = 48; wethers, n = 48) and BW, housed in 24 pens (4 lambs
      per pen), and used in a 92-d feedlot trial (initial BW = 26.4 +/- 9.3 kg). Lambs
      were fed 1 of 4 dietary treatments 1) 0% DDGS, 2) 20% DDGS, 3) 40% DDGS, or 4)
      60% DDGS. The DDGS replaced primarily corn, and diets were fed as a complete
      pellet. There was a quadratic effect of DDGS inclusion on ADG; lambs fed the 20%
      DDGS diet had the greatest (P = 0.04) gains at 0.358 kg/d. This effect on ADG led
      to a quadratic (P = 0.03) effect of DDGS on final BW. Increasing dietary DDGS did
      not affect (P > 0.13) DMI and resulted in a linear (P = 0.02) decrease in G:F. In
      the liver, S increased linearly (P = 0.05), whereas Cu decreased linearly (P <
      0.01) with increasing dietary DDGS; other liver minerals were not affected (P >
      0.05). Carcass backfat, yield grade, and marbling score were not affected (P >
      0.05) by dietary DDGS. In Exp. 2, twenty-four lambs (initial BW = 43.0 +/- 4.4
      kg) were used in a metabolism study. Lambs were adapted to the same diets
      described above for 17 d before a 5-d sampling period during which total feces
      and urine were collected. Apparent digestibility of dietary DM decreased linearly
      (P < 0.01) with increasing dietary inclusion of DDGS. Digestibility of fat
      followed a similar pattern, whereas N, S, and P absorption increased linearly (P
      < 0.03) with increasing dietary DDGS. The digestibility of NDF was not affected
      (P > 0.05) by dietary treatment. Apparent retentions (as a percentage of intake)
      of N, K, Mg, Cu, Fe, and Zn were not affected (P > 0.05) by dietary DDGS
      inclusion, whereas the retention of S and P decreased (P < 0.04). Daily urine
      output increased linearly (P < 0.01) and urine pH decreased linearly (P < 0.01)
      with increasing DDGS (urine pH was 7.46, 5.86, 5.52, and 5.32 for treatments 1 to
      4, respectively). These data suggest urine is a major route for excretion of acid
      when high-S diets containing DDGS are fed. Increases in dietary DDGS resulted in
      decreased digestion of DM and fat, which may be partially responsible for
      decreased lamb feedlot performance for 40 and 60% dietary DDGS when compared with
      20% DDGS.

PMID- 22147467
TI  - Natural contamination of dietary rice straw with zearalenone and urinary
      zearalenone concentrations in a cattle herd.
AB  - The present study was conducted to 1) identify the natural source of feed
      contamination by zearalenone (ZEN), which was suspected to have caused
      persistently increased urinary ZEN concentrations in one of our experimental
      cattle herds, and 2) evaluate the effects of intervention against this source of
      contamination. As an experimental model, a fattening Japanese Black cattle herd
      showing persistently increased urinary ZEN concentrations was identified. Urinary
      ZEN concentrations of cows fed with new rice straw (experimental group, n = 6)
      vs. cows that continued to feed on the old rice straw (control group, n = 4) were
      measured at the start (d 1) and at 2 wk (d 14) after the onset of feeding with
      straw. In addition, the ZEN concentration in feed and water samples was measured
      by using both the ELISA and HPLC methods. Furthermore, isolation and
      identification of fungi from rice straw and concentrate feed samples were
      performed. The urinary ZEN concentration [ZEN (pg/mL)/creatinine (mg/mL) = pg/mg
      of creatinine] of cows fed with new rice straw was significantly (P < 0.05) less
      (843 pg/mg of creatinine) than that of cows fed with old rice straw (15,951 pg/mg
      of creatinine). On both d 1 and 14, the ZEN concentrations of old rice straw were
      greater than those of new rice straw. In addition, fungal colonies were observed
      in the culture media that was obtained from the old rice straw suspected of ZEN
      contamination, but not in the culture media from new rice straw or other feed
      samples. In conclusion, our field trials clearly indicate that the rice straw fed
      to the cows was naturally contaminated with ZEN, and that the monitoring of
      urinary ZEN concentrations could prove to be a useful tool for detecting the
      exposure of cattle to ZEN contamination at the farm level.

PMID- 22147468
TI  - A third-generation esterase inoculant alters fermentation pattern and improves
      aerobic stability of barley silage and the efficiency of body weight gain of
      growing feedlot cattle.
AB  - This study investigated the effects of a mixed bacterial inoculant possessing
      ferulic acid esterase (FAE) activity on silage fermentation characteristics,
      aerobic stability, and growth performance of growing feedlot steers. Whole-crop
      barley (Hordeum vulgare L.) forage (35% DM) was chopped and ensiled without a
      silage inoculant (UN) or with a mixed bacterial culture containing 1.0 * 10(11)
      cfu/g of Lactobacillus buchneri LN4017 that produces FAE, 2.0 * 10(10) cfu/g of
      Lactobacillus plantarum LP7109, and 1.0 * 10(10) cfu/g of Lactobacillus casei
      LC3200 at a combined rate of 1.3 * 10(5) cfu/g of fresh forage (IN) in mini and
      Ag-Bag (Ag-Bag Int. Ltd., Warrenton, OR) silos. Silages from the mini silos were
      assessed for the effect of inoculation on fermentation characteristics and
      aerobic stability, whereas silages from Ag-Bags were used to formulate 2 barley
      silage-based total mixed rations (UN and IN) that were fed to growing feedlot
      steers for 112 d. The IN silage exhibited a homolactic fermentation during the
      first 7 d of ensiling as reflected by an increased (P <= 0.02) lactic acid
      concentration and an accelerated rate (P < 0.01) of pH decline. Thereafter,
      fermentation of IN silage became more heterolactic, resulting in greater
      concentrations of acetic acid (P < 0.01) and pH (P < 0.01) but less (P < 0.01)
      lactic acid than UN silage. Inoculation did not affect DM losses (P = 0.52) from
      mini silos. The IN silage remained stable during 21 d, but temperature and yeasts
      counts in the UN silage increased after 5 d of aerobic exposure. Growing steers
      fed the IN silage diet had superior (P = 0.03) feed conversion efficiency
      compared with those fed UN silage. Inoculation of whole-crop barley silage with a
      mixed culture of homolactic lactic acid-producing bacteria and FAE-producing L.
      buchneri at ensiling changed fermentation from a homolactic to a heterolactic
      form during ensiling and improved aerobic stability of the silage and efficiency
      of BW gain of growing feedlot steers.

PMID- 22147469
TI  - Effects of sequential feeding of beta-adrenergic agonists on cull cow
      performance, carcass characteristics, and mRNA relative abundance.
AB  - The objectives of this study were to determine the effects of supplementation
      with a single beta-adrenergic agonist (beta-AA) or a sequence of beta-AA on cow
      performance, carcass characteristics, and mRNA relative abundance of cull cows
      implanted and fed a concentrate diet. Sixty cull cows were implanted with Revalor
      200 (200 mg of trenbolone acetate and 20 mg of estradiol) and assigned to 1 of 4
      treatments (n = 15/treatment): CON = fed a concentrate diet only; RH =
      supplemented with ractopamine-HCl for the last 25 d before slaughter; ZH =
      supplemented with zilpaterol-HCl for 20 d before a 3-d withdrawal before
      slaughter; RH + ZH = supplemented with RH for 25 d, followed by ZH for 20 d
      before a 3-d withdrawal before slaughter. Ractopamine-HCl was supplemented at a
      dose of 200 mg.animal(-1).d(-1), and ZH was supplemented at 8.33 mg/kg (100% DM
      basis) of feed. All cows were fed a concentrate diet for 74 d. Each treatment had
      5 cows per pen and 3 replicate pens. Body weights were collected on d 1, 24, 51,
      and 72. Muscle biopsies from the LM were collected on d 24, 51, and at slaughter
      from a subsample of 3 cows per pen. Carcass traits were evaluated postslaughter.
      The 2 ZH treatments averaged 15.3 kg more BW gain, 0.20 kg greater ADG, and 7.8
      cm(2) larger LM area than CON and RH treatments, and 21 kg more HCW than CON, but
      these differences were not significant (P > 0.10), likely due to a sample size of
      n = 15/treatment. The sequence of RH followed by ZH tended to optimize the
      combination of HCW, LM area, percent intramuscular fat, and lean color and
      maturity compared with the ZH treatment. Abundance of beta(2)-adrenergic receptor
      (AR) mRNA was not altered in the RH + ZH treatment during RH supplementation from
      d 24 to 51 of feeding. However, the abundance of beta(2)-AR mRNA increased (P <
      0.05) the last 23 d of feeding for the RH treatment and tended (P = 0.10) to
      increase in ZH cows during ZH supplementation. For all cows, abundance of type
      IIa myosin heavy chain (MHC-IIa) mRNA decreased (P < 0.05) after 24 d of feeding.
      Abundance of MHC-IIx mRNA increased (P < 0.05) for ZH and RH + ZH treatments the
      last 23 d of feeding during ZH supplementation. Although few significant
      differences were observed in performance or carcass traits, mRNA quantification
      indicated that beta-AA supplementation elicited a cellular response in cull cows.
      Implanting and feeding cull cows for 74 d, regardless of beta-AA supplementation,
      added economic value by transitioning cows from a cull cow to what is referred to
      in industry as a white cow market in which cows have white fat resulting from
      grain feeding.

PMID- 22147470
TI  - Maternal low-dose porcine somatotropin treatment in late gestation increases
      progeny weight at birth and weaning in sows but not in gilts.
AB  - Birth weight positively predicts postnatal growth and performance in pigs and can
      be increased by sustained maternal porcine ST (pST) treatment from d 25 to 100 of
      pregnancy (term ~115 d). The objective of this study was to test whether a
      shorter period of maternal pST treatment in late pregnancy (d 75 to 100) could
      also increase birth and weaning weights of progeny under commercial conditions.
      Gilts (parity 0) and sows (parities 2 and 3) were not injected (controls) or
      injected daily with pST (gilts: 2.5 mg*d(-1), sows: 4.0 mg*d(-1), both ~13 to 14
      MUg*kg(-1)*d(-1)) from d 75 to 100 of pregnancy. Litter size and BW were recorded
      at birth and weaning, and dams were followed through the subsequent mating and
      pregnancy. Maternal pST injections from d 75 to 100 increased litter average
      progeny weight at birth (+96 g, P = 0.034) and weaning (+430 g, P = 0.038) in
      sows, but had no effect on progeny weight in gilts (each P > 0.5). Maternal pST
      treatment did not affect numbers of live-born piglets and increased numbers of
      stillborn piglets in sows only (+0.4 pigs/litter, P = 0.034). Maternal pST
      treatment did not affect subsequent reproduction of dams. Together with our
      previous data, these results suggest that sustained increases in maternal pST are
      required to increase fetal and postnatal growth in gilt progeny, but that
      increasing maternal pST in late pregnancy may only be an effective strategy to
      increase fetal and possibly postnatal growth in sow progeny.

PMID- 22147471
TI  - Immunization of beef heifers against gonadotropin-releasing hormone prevents
      luteal activity and pregnancy: Effect of conjugation to different proteins and
      effectiveness of adjuvants.
AB  - Three experiments were conducted to evaluate methods of immunization against GnRH
      on antibody titer, luteal activity, and pregnancy in beef heifers. Experiment 1
      evaluated the efficacy of adjuvants with 30 heifers. Control heifers were
      immunized against human serum albumin (HSA) emulsified in Freund's complete
      adjuvant (FCA). The other 4 treatments contained GnRH conjugated to HSA (HSA
      GnRH) emulsified in FCA, Freund's incomplete adjuvant (FIA), DEAE dextran (DD) +
      mineral oil (MO), or DD+FIA. Treatment was in the mammary gland for all
      experiments. Titers against GnRH for heifers immunized against HSA-GnRH with FCA,
      DD+MO, or DD+FIA were greater than titers for HSA-GnRH with FIA or control
      heifers (P < 0.01). Body weight was reduced (P < 0.05) in control and FCA heifers
      compared with FIA, DD+MO, and DD+FIA heifers. Heifers immunized with DD+MO and
      DD+FIA had fewer granulomas in mammary glands than heifers treated with FCA (P <
      0.01). In Exp. 2, 36 heifers were used to determine the effect of the protein
      conjugated to GnRH on titers against GnRH. Heifers (6/treatment) received a
      primary immunization against GnRH conjugated to HSA (HSA-GnRH), ovalbumin (OA
      GnRH), or keyhole limpet hemocyanin (KL-GnRH), or heifers were immunized against
      each carrier protein. Antigens were emulsified in DD+FIA. Immunization of heifers
      against OA-GnRH, KL-GnRH, or HSA-GnRH suppressed luteal activity (P < 0.01) for
      23, 16, and 12 wk, respectively, and antibody titers against GnRH were greater (P
      < 0.01) for 19, 5, and 7 wk, respectively, compared with heifers immunized
      against the carrier proteins. In Exp. 3, 90 heifers were used to determine the
      effect of immunization against GnRH on ovarian activity and pregnancy rate.
      Heifers (30/treatment) received a primary and 2 or 3 booster immunizations
      against GnRH conjugated to OA, and controls received a primary and 2 booster
      immunizations against OA. All antigens were emulsified in DD+FIA. At 8 wk after
      primary immunization, heifers were exposed to fertile bulls for 24 wk. Pregnancy
      rate was less (P < 0.01) for 3-booster heifers (13%) compared with control (83%)
      and 2-booster (62%) heifers. We conclude that immunization against GnRH,
      conjugated to OA and emulsified in DD+FIA, does not influence ADG and produces
      sufficient titers against GnRH to prevent estrous cycles with few mammary
      granulomas. Immunization against GnRH with 3 booster immunizations prevented
      luteal activity and pregnancy in most beef heifers for more than 4 mo.

PMID- 22147473
TI  - Wet distillers grains plus solubles concentration in steam-flaked-corn-based
      diets: Effects on feedlot cattle performance, carcass characteristics, nutrient
      digestibility, and ruminal fermentation characteristics.
AB  - Two experiments were conducted to determine the effects of wet distillers grain
      plus solubles (WDG; <15% sorghum grain) concentration in steam-flaked corn (SFC)
      diets on feedlot performance, carcass characteristics, ruminal fermentation, and
      diet digestibility. In Exp. 1, six hundred crossbred steers (364 +/- 35 kg of BW)
      were used in a randomized complete block design with 8 replications/treatment.
      Dietary treatments consisted of a dry-rolled corn (DRC) control diet without WDG,
      a SFC control without WDG, and SFC with 4 WDG concentrations (15, 30, 45, 60% DM
      basis) replacing SFC, cottonseed meal, urea, and yellow grease. Final BW, ADG,
      G:F, HCW, and 12th-rib fat depth were greater (P <= 0.05) for SFC compared with
      DRC. Dry matter intake tended (P = 0.06) to be greater for DRC compared with SFC.
      Final BW, ADG, G:F, HCW, 12th-rib fat depth, and marbling score decreased
      linearly (P < 0.01) with increasing WDG concentration. In Exp. 2, six ruminally
      and duodenally cannulated crossbred steers (481 +/- 18 kg of BW) were used in a 6
      * 6 Latin square design using the same diets as Exp. 1. Ruminal, postruminal, and
      total tract OM and NDF digestibility were not different (P > 0.14) for DRC
      compared with SFC. Ruminal and total tract starch digestibility were greater (P <
      0.01) for SFC compared with DRC. Dry matter and OM intake were not different (P
      >= 0.43) among WDG treatments. Ruminal and total tract OM digestibility decreased
      linearly (P < 0.01) with increasing WDG concentration. Intake, ruminal
      digestibility, and total tract digestibility of NDF increased linearly (P < 0.01)
      with increasing WDG concentration. Starch intake decreased linearly (P < 0.01)
      with increasing WDG concentration. Ruminal starch digestibility increased (P =
      0.01) with increasing concentration of WDG. Total tract starch digestibility
      decreased quadratically (P < 0.01) with increasing concentration of WDG. Feeding
      SFC improved steer performance compared with DRC. The concentration of WDG and
      corn processing method influences nutrient digestibility and ruminal
      fermentation. The addition of WDG in SFC-based diets appears to negatively affect
      animal performance by diluting the energy density of the diet.

PMID- 22147474
TI  - Relationship between the activity of mitochondrial respiratory chain complexes
      and feed efficiency in fat-tailed Ghezel lambs.
AB  - This study was conducted to investigate relationships between mitochondrial
      respiratory chain complex activities, feed efficiency, and carcass traits in
      sheep. A group of Ghezel male lambs sired by a single ram were randomly allotted
      to individual pens. The lambs were fed ad libitum with a fattening diet
      containing 30% roughage (corn silage and alfalfa hay) and 70% concentrate for 70
      d to individually phenotype each lamb for feed conversion ratio (FCR), adjusted
      FCR (aFCR), and residual feed intake (RFI). The lambs were then humanely killed
      and the liver, abdominal fat, pelvic fat, cardiac fat, warm carcass weight, and
      cold carcass weight, as well as the cross-sectional area of the LM and the fat
      depth over the 12th rib, were determined. A portion of LM was obtained to
      determine mitochondrial protein and respiratory chain complex activities
      (complexes I to V). Statistical analysis was carried out based on lambs
      exhibiting high and low RFI (n = 8), FCR (n = 8), or aFCR (n = 8) phenotypes. The
      lambs exhibiting the high-RFI phenotype consumed 110 g more feed daily (P < 0.05)
      than did the phenotype exhibiting low RFI, with no difference in ADG. Conversely,
      there was no difference in feed intake between the low- or high-FCR groups, but
      sheep exhibiting the low-FCR phenotype gained 70 g more (P < 0.05) per day
      compared with those exhibiting the high-FCR phenotype. It was determined that all
      5 respiratory chain complex activities were greater (P < 0.05) in sheep
      exhibiting the low-RFI phenotype compared with those exhibiting the high-RFI
      phenotype, with significant (P < 0.001) negative correlation coefficients between
      RFI and respiratory chain complex activity. When efficiency was assessed using
      FCR, only activities of respiratory chain complexes III, IV, and V were less (P <
      0.05) in the low-FCR phenotype compared with the high-FCR phenotype, and there
      were no differences (P > 0.1) in respiratory chain complex activities between
      groups when FCR was adjusted for metabolic BW (aFCR). There were no differences
      (P > 0.1) in carcass traits among any of the feed efficiency phenotypes. The
      results suggest that the inclusion of respiratory chain complex activities in
      breeding programs may be helpful in selecting for sheep exhibiting the low-RFI
      phenotype.

PMID- 22147475
TI  - Bovine sire selection based on maintenance energy affects muscle fiber type and
      meat color of F1 progeny.
AB  - A total of 42 F(1) Red Angus progeny from sires divergent in maintenance energy
      (ME(M)) EPD were analyzed to determine whether selecting for sire ME(M) would
      alter end-product meat quality. Data from animals were grouped based on the
      divergence of the ME(M) EPD of their sire from the Red Angus Association-reported
      breed average and defined as either high or low, the assumption being that high
      ME(M) cattle are less efficient because their maintenance requirements represent
      a larger proportion of their dietary intake. Steer progeny (n = 7) from the high
      group produced bottom round steaks with a greater a* (redness) color value (P =
      0.02) after 5 d in a simulated retail display when compared with bottom round
      steaks from the low group (n = 18). Bottom round steaks from the high group had a
      greater b* (yellowness) color value at d 1 (P = 0.03) and d 5 (P = 0.01) of
      retail display. Samples from the biceps femoris were taken at 12 mo (from both
      steers and heifers) and 15 mo (from steers only) of age for fiber type proportion
      analysis. At 12 mo of age, steers from the low group had more type I fibers (P =
      0.02), whereas steers from the high group had more type IIb fibers (P = 0.01).
      Furthermore, samples from steers in the low group at 15 mo had more type I fibers
      (P = 0.02), and steers from the high group maintained more type IIb fibers (P =
      0.02). No changes in fiber type proportions were observed between the high- and
      low-ME(M) EPD heifers (n = 17). Relative mRNA abundance of genes involved in the
      synthesis, storage, and breakdown of glycogen were analyzed as a variable
      important for meat quality, but no statistical differences were observed. At 12
      mo age, glycogenin (glyc) was negatively correlated with the proportion of type
      IIa fibers (r = -0.32 and P = 0.12) as well as with the proportion of type IIb
      fibers (r = -0.42 and P = 0.03) in the biceps femoris of the steers. In samples
      taken from the biceps femoris at 15 mo age, glyc was negatively correlated with
      the proportion of type IIa fibers (r = -0.42 and P = 0.03) in the steers. This
      indicates that relative mRNA expression of glyc may serve as a marker of muscle
      glycogen storage capacity in steers. Thus, selection for efficient Red Angus beef
      cattle based on sire ME(M) EPD does not adversely affect meat quality in F(1)
      progeny, based on the variables assessed in this study. Furthermore, selection
      for progeny from low-ME(M) EPD sires may improve fresh meat quality within Red
      Angus beef cattle.

PMID- 22147478
TI  - Electrical stimulation affects metabolic enzyme phosphorylation, protease
      activation, and meat tenderization in beef.
AB  - The objective of this study was to investigate the response of sarcoplasmic
      proteins in bovine LM to low-voltage electrical stimulation (ES; 80 V, 35 s)
      after dressing and its contribution to meat tenderization at an early postmortem
      time. Proteome analysis showed that ES resulted in decreased (P < 0.05)
      phosphorylation of creatine kinase M chain, fructose bisphosphate aldolase C-A,
      beta-enolase, and pyruvate kinase at 3 h postmortem. Zymography indicated an
      earlier (P < 0.05) activation of MU-calpain in ES muscles. Free lysosomal
      cathepsin B and L activity increased faster (P < 0.05) in ES muscles up to 24 h.
      Immunohistochemistry and transmission electron microscopy further indicated that
      lysosomal enzymes were released at an early postmortem time. Electrical
      stimulation also induced ultrastructural disruption of sarcomeres. In addition,
      ES accelerated (P < 0.05) the depletion of ATP, creatine phosphate, and glycogen,
      as well as a pH decline and the more preferred pH/temperature decline mode.
      Finally, ES accelerated meat tenderization, resulting in lesser (P < 0.05) shear
      force values than the control over the testing time. A possible relationship was
      suggested between a change in the phosphorylation of energy metabolic enzymes and
      the postmortem tenderization of beef. Our results suggested the possible
      importance of the activation of MU-calpain, phosphorylation of sarcoplasmic
      proteins, and release of lysosomal enzymes for ES-induced tenderization of beef
      muscle.

PMID- 22147479
TI  - Increasing energy and lysine in diets for growing-finishing pigs in hot
      environmental conditions: consequences on performance, digestibility, slurry
      composition, and gas emission.
AB  - The influence of dietary nutrient concentration on growth performance, manure
      composition, and gas emission was studied in pigs in hot environmental
      conditions. A total of 64 intact males and 64 females [(Landrace * Large White) *
      Pietrain] weighing 63.1 +/- 9.7 kg were divided into 2 dietary treatments: high
      (HD: 14.39 MJ of DE/kg and 1.11% Lys) and low (LD: 13.97 MJ of DE/kg and 1.01%
      Lys) in energy and Lys contents. Pigs were allocated to 32 split-sex pens with 4
      pigs/pen and 16 pens/treatment. Average productive performance was recorded for
      41 d (phase 1). After phase 1, 12 females of 103.3 +/- 3.15 kg (6 per treatment)
      were selected and housed individually, and feces and slurry were collected during
      3 and 4 consecutive days, respectively, to calculate nutrient digestibility and
      measure gas emissions (phase 2). For gas emission measurements, slurry was pooled
      by treatment and stored for 76 d. Initial composition of slurry and pH were
      analyzed. Maximum and minimum temperatures registered in the barn throughout the
      growing period were 35.1 and 18.1 degrees C, respectively. Animals fed the HD
      diet grew more efficiently than pigs fed the LD diet (G:F, 0.43 vs. 0.40; SEM =
      0.01; P < 0.05). Fat digestibility was greater in HD compared with LD pigs (88.0
      vs. 84.9%; SEM = 0.9; P < 0.05). Slurry from pigs fed the LD diet showed greater
      DM, OM, total N, and VFA contents than slurry from pigs fed the HD diet.
      Cumulative NH(3), CO(2), and especially CH(4) emissions were greater in the HD
      slurry compared with the LD slurry (192.4 vs. 210.g of NH(3)/m(3); 2,712 vs.
      3,210 g of CO(2)/m(3); 1,502 vs. 2,647 mL of CH(4)/kg of OM). Increasing feed
      density in the present study led to a more efficient growth, a decreased nutrient
      concentration in the slurry, and a greater gas emission.

PMID- 22147480
TI  - Physiological and behavioral responses of sheep to gaseous ammonia.
AB  - Ammonia can accumulate in highly stocked sheep accommodation, for example during
      live export shipments, and could affect sheep health and welfare. Thus, the
      objective of this experiment was to test the effects of 4 NH(3) concentrations, 4
      (control), 12, 21, and 34 mg/m(3), on the physiology and behavior of wether
      sheep. Sheep were held for 12 d under a micro-climate and stocking density
      similar to shipboard conditions recorded on voyages from Australia to the Middle
      East during the northern hemispheric summer. Ammonia increased macrophage
      activity in transtracheal aspirations, indicating active pulmonary inflammation;
      however, it had no effect (P > 0.05) on hematological variables. Feed intake
      decreased (P = 0.002) in proportion to ammonia concentration, and BW gain
      decreased (P < 0.001) at the 2 greatest concentrations. Exposure to ammonia
      increased (P = 0.03) the frequency of sneezing, and at the greatest ammonia
      concentration, sheep were less active, with less locomotion, pawing, and panting.
      Twenty-eight days after exposure to NH(3), the pulmonary macrophage activity and
      BW of the sheep returned to that of sheep exposed to only 4 mg/m(3). It was
      concluded that NH(3) induced a temporary inflammatory response of the respiratory
      system and reduced BW gain, which together indicated a transitory adverse effect
      on the welfare of sheep.

PMID- 22147481
TI  - Digestibility of phosphorus by growing pigs of fermented and conventional soybean
      meal without and with microbial phytase.
AB  - An experiment was conducted to test the hypothesis that the apparent total tract
      digestibility (ATTD) and the standardized total tract digestibility (STTD) of P
      in fermented soybean meal (FSBM) are greater than in conventional soybean meal
      (SBM-CV) when fed to growing pigs. Four diets were formulated to contain FSBM or
      SBM-CV and either 0 or 800 units/kg of microbial phytase. The only sources of P
      in these diets were FSBM and SBM-CV. A P-free diet to estimate basal endogenous
      losses of P was also formulated. Thirty barrows (initial BW: 14.0 +/- 2.3 kg)
      were placed in metabolism cages and allotted to 5 diets in a randomized complete
      block design with 6 pigs per diet. Feces were collected for 5 d after a 5-d
      adaptation period. All samples of ingredients, diets, and feces were analyzed for
      P, and values for ATTD and STTD of P were calculated. Results indicated that the
      basal endogenous P losses were 187 mg/kg of DMI. As phytase was added to the
      diet, the ATTD and STTD of P increased (P < 0.01) from 60.9 to 67.5% and from
      65.5 to 71.9%, respectively, in pigs fed FSMB. Likewise, addition of phytase to
      SBM-CV increased (P < 0.01) the ATTD and STTD of P from 41.6 to 66.2% and from
      46.1 to 71.4%, respectively. The ATTD and STTD of P were greater (P < 0.01) in
      FSBM than in SBM-CV when no phytase was used, but that was not observed when
      phytase was added to the diet (soybean meal * phytase interaction, P < 0.01). In
      conclusion, the ATTD and STTD of P in FSBM was greater than SBM-CV when no
      microbial phytase was added, but when phytase was added to the diets, no
      differences between FSBM and SBM-CV were observed in the ATTD and STTD of P.

PMID- 22147482
TI  - Constriction of bovine vasculature caused by endophyte-infected tall fescue seed
      extract is similar to pure ergovaline.
AB  - Ergovaline has been extensively used to study vasoactive effects of endophyte-
      (Neotyphodium coenophialum) infected tall fescue (Lolium arundinaceum). However,
      initial results indicated that an extract of toxic tall fescue seed (E+EXT) is
      more potent than ergovaline alone in a right ruminal artery and vein bioassay.
      The E+EXT induced a greater contractile response than an equal concentration of
      ergovaline alone in the ruminal artery of heifers (P = 0.018). This led to a
      hypothesis that other compounds in the seed extract contribute to
      vasoconstriction. Thus, experiments were conducted to determine if vasoactivity
      of an E+EXT is different from a mixture of ergot alkaloids (ALK; ergovaline,
      ergotamine, ergocristine, ergocryptine, ergocornine, ergonovine, and lysergic
      acid) of similar concentrations and to determine if the vasoactivity of an E+EXT
      differs from an endophyte-free tall fescue seed extract (E-EXT). Segments of
      lateral saphenous vein and right ruminal artery and vein were collected from
      Holstein steers (n = 6) shortly after slaughter. Vessels were cleaned of excess
      connective tissue and fat and sliced into segments that were suspended in a
      multimyograph chamber with 5 mL of continually oxygenated Krebs-Henseleit buffer,
      equilibrated for 90 min, and exposed to a reference compound (120 mM KCl for
      ruminal vessels and 0.1 mM norepinephrine for saphenous vein). Increasing
      concentrations of each treatment (E+EXT, E-EXT, ALK, and ergovaline) were added
      to the respective chamber every 15 min after buffer replacement. Data were
      normalized as a percentage of maximal contractile response of the reference
      compound and fit to a sigmoidal concentration response curve. Ergovaline, ALK,
      and E+EXT induced similar responses in the saphenous vein, ruminal artery, and
      ruminal vein. The E+EXT displayed a smaller EC(50) (half maximal effective
      concentration) than ergovaline or ALK in the saphenous vein and ruminal vein (P <
      0.008), but not the ruminal artery (P = 0.31). Extrapolated maximum response was
      greatest in the saphenous vein for ergovaline, least for E+EXT, and intermediate
      for ALK (P < 0.0001). The E-EXT did not induce a contractile response in any
      vessel tested (P > 0.1). Data from this study indicate that ergovaline is largely
      responsible for the locally induced vasoconstriction of bovine vasculature
      observed with endophyte-infected tall fescue.

PMID- 22147483
TI  - Prediction of physical and chemical body compositions of purebred and crossbred
      Nellore cattle using the composition of a rib section.
AB  - The goal of this research was to develop empirical equations to predict chemical
      and physical compositions of the carcass and the body using the composition of
      the 9th- to 11th-rib section (rib(9-11)) and other measurements. A database (n =
      246) from 6 studies was developed and comprised 37 bulls (BU), 115 steers (STR),
      and 94 heifers (HF), of which 132 were Nellore (NEL), 76 were NEL * Angus
      crossbreds (NA), and 38 were NEL * Simmental crossbreds (NS). The right half
      carcass and the rib(9-11) from the left half carcass were analyzed for ether
      extract (EE), CP, and water. The remaining components were chemically analyzed to
      determine the composition of the body. A stepwise procedure was used to determine
      the variable inclusion in the regression models. The variables included were EE
      in the rib(9-11) (EER; %), CP in the rib(9-11) (CPR; %), water in the rib(9-11)
      (WR; %), visceral fat (VF; %; KPH and mesenteric fats), organs plus viscera (OV;
      %), carcass dressing percentage (CD; %), cold carcass weight (kg), and empty BW
      (EBW; kg). No sex or breed effects were found on EE and CP compositions of the
      carcass (C(EE) and C(CP), respectively; %); the equations were as follows: C(EE)
      = 4.31 + 0.31 * EER + 1.37 * VF [n = 241; R(2) = 0.83; mean square error (MSE) =
      4.53] and C(CP) = 17.92 + 0.60 * CPR - 0.17 * CD (n = 238; R(2) = 0.50; MSE =
      1.58). Breed affected water content in the carcass (C(W), %); the equations were
      as follows: C(W) = 48.74 + 0.28 * WR - 0.017 * EBW for NEL; C(W) = 46.69 + 0.32 *
      WR - 0.017 * EBW for NA; and C(W) = 38.06 + 0.48 * WR - 0.017 * EBW for NS (n =
      243; R(2) = 0.67; MSE = 5.17). A sex effect was found on body chemical EE
      composition (BW(EE)); the equations were as follows: BW(EE) = 2.75 + 0.33 * EER +
      1.80 * VF for BU; BW(EE) = 1.84 + 0.33 * EER + 1.91 * VF for STR; and BW(EE) =
      4.77 + 0.33 * EER + 1.28 * VF for HF (n = 243; R(2) = 0.89; MSE = 3.88). No sex
      or breed effects were found on CP composition in the body (BW(CP)); the equation
      was as follows: BW(CP) = 14.38 + 0.24 * CPR (n = 240; R(2) = 0.59; MSE = 1.06). A
      sex effect was found for body water content (BW(W)); the equations were as
      follows: BW(W) = 38.31 + 0.33 * WR - 1.09 * VF + 0.50 * OV for BU; BW(W) = 45.67
      + 0.25 * WR - 1.89 * VF + 0.50 * OV for STR; and BW(W) = 31.61 + 0.47 * WR - 1.06
      * VF + 0.50 * OV for HF (n = 241; R(2) = 0.81; MSE = 3.84). The physical carcass
      composition indicated a breed effect on all components and a sex effect for fat
      in the carcass. We conclude that body and carcass compositions can be estimated
      with rib(9-11) for purebred and crossbred NEL animals, but specific equations
      have to be developed for different groups of animals.

PMID- 22147485
TI  - Vitamin E supplementation in beef finishing diets containing 35% wet distillers
      grains with solubles: feedlot performance and carcass characteristics.
AB  - Supplementation of vitamin E has indications for improving cattle health,
      performance, and retail characteristics when included in grain-based diets. This
      experiment was conducted to determine performance and carcass characteristics of
      steers fed diets containing wet distillers grains with solubles (WDGS) and
      supplemented with vitamin E. Steers of mixed Bos indicus and Bos taurus breeding
      (n = 199; BW = 363 +/- 32 kg) were blocked by BW and assigned to 1 of 4
      supplemental vitamin E (VITE) treatments [0 (control), 125, 250, and 500
      IU.steer(-1).d(-1)], which were fed for the last 97 d of the feeding period. Two
      blocks were on feed 129 d, and 3 blocks were fed for 150 d. Steers were fed a dry
      rolled corn-based finishing diet with 35% WDGS (DM basis). Individual BW were
      measured initially, the initial day of vitamin E supplementation, and the day of
      slaughter. Carcass weights were collected at slaughter, and carcass data were
      collected after a 36-h chill. Body weight and ADG were not affected by VITE (P >=
      0.34). There was a tendency for a linear (P = 0.08) increase in carcass-adjusted
      BW with increasing VITE. Use of carcass-adjusted final BW resulted in a linear
      increase (P = 0.04) in ADG with increasing VITE. Pre-vitamin E and vitamin E
      feeding period DMI were not affected (P >= 0.24) by VITE, but there was a
      tendency (P = 0.08) for a linear increase in overall DMI with increasing VITE. No
      difference (P >= 0.29) occurred in G:F measures using BW gains, but G:F using
      carcass-adjusted BW gains resulted in a trend (P = 0.11) for G:F to increase
      linearly with increasing VITE. Hot carcass weights tended (P = 0.08) to increase
      linearly with increasing dietary vitamin E. Vitamin E supplementation resulted in
      no effects (P >= 0.13) on measured carcass characteristics. Calculated yield
      grades (YG) were also not affected (P >= 0.37). However, the distribution of
      calculated YG resulted in a quadratic effect (P = 0.02) for YG 3 with the control
      and 500 VITE being greater than the 2 intermediate amounts. However, the
      percentage of carcasses grading YG 3 or less were not affected by vitamin E
      supplementation (P = 0.64). No differences were observed in the distribution of
      quality grades based on marbling scores (P >= 0.57). Data from this study suggest
      that vitamin E supplemented above basal requirements during the last 97 d of the
      feeding period in finishing diets containing 35% WDGS results in slight to no
      effect on animal performance or carcass characteristics.

PMID- 22147486
TI  - Associations between weather conditions during the first 45 days after feedlot
      arrival and daily respiratory disease risks in autumn-placed feeder cattle in the
      United States.
AB  - Data on associations between weather conditions and bovine respiratory disease
      (BRD) morbidity in autumn-placed feedlot cattle are sparse. The goal of our study
      was to quantify how different weather variables during corresponding lag periods
      (considering up to 7 d before the day of disease measure) were associated with
      daily BRD incidence during the first 45 d of the feeding period based on a post
      hoc analysis of existing feedlot operational data. Our study population included
      1,904 cohorts of feeder cattle (representing 288,388 total cattle) that arrived
      to 9 US commercial feedlots during September to November in 2005 to 2007. There
      were 24,947 total cases of initial respiratory disease (animals diagnosed by the
      feedlots with BRD and subsequently treated with an antimicrobial). The mean
      number of BRD cases during the study period (the first 45 d after arrival) was
      0.3 cases per day per cohort (range = 0 to 53.0), and cumulative BRD incidence
      risks ranged from 0 to 36% within cattle cohorts. Data were analyzed with a
      multivariable mixed-effects binomial regression model. Results indicate that
      several weather factors (maximum wind speed, mean wind chill temperature, and
      temperature change in different lag periods) were significantly (P < 0.05)
      associated with increased daily BRD incidence, but their effects depended on
      several cattle demographic factors (month of arrival, BRD risk code, BW class,
      and cohort size). In addition, month and year of arrival, sex of the cohort, days
      on feed, mean BW of the cohort at entry, predicted BRD risk designation of the
      cohort (high or low risk), cohort size, and the interaction between BRD risk code
      and arrival year were significantly (P < 0.05) associated with daily BRD
      incidence. Our results demonstrate that weather conditions are significantly
      associated with BRD risk in populations of feedlot cattle. Defining these
      conditions for specific cattle populations may enable cattle health managers to
      predict and potentially manage these effects more effectively; further, estimates
      of effects may contribute to the development of quantitative predictive models
      for this important disease syndrome.

PMID- 22147487
TI  - Relationships of barometric pressure and environmental temperature with incidence
      of parturition in beef cows.
AB  - The relationship between barometric pressure (BARO) and maximum (MAX_T) and
      minimum (MIN_T) environmental temperatures with the incidence of parturition in
      beef cows was examined through exploratory data analysis. Spring- and fall
      calving records from a 5-yr period (2005 through 2009) collected at the
      University of Arkansas, Livestock and Forestry Research Station (Batesville) and
      the Department of Animal Science Savoy Research Unit (Savoy, AR) were used. All
      cows were multiparous, predominantly Angus, and naturally bred. During this
      period, 2,210 calves were born over a cumulative 1,547 d. Local weather station
      BARO and MAX_T and MIN_T data were obtained from the Southern Regional Climate
      Center, Louisiana State University, Baton Rouge. The combined calving record and
      climate variables were used to determine differences in BARO, MAX_T, and MIN_T on
      d 0 (d of calving) and -1, -2, or -3 d, respectively, before calving occurred
      (CALFD) or did not occur (NOCALFD). Location and season also were included in the
      model. For fall-calving cows, BARO on d 0 and -1, -2, or -3 was not different
      between CALFD and NOCALFD (P > 0.10). For spring-calving cows, BARO on d 0, -1, 
      2, and -3 was greater (P < 0.05) for CALFD compared with NOCALFD. The MAX_T was
      greater on d -1 (24.4 vs. 22.9 degrees C) and -3 (24.8 vs. 23.4 degrees C) for
      CALFD in the fall compared with NOCALFD (P < 0.05). No differences were detected
      in the fall for MAX_T on d 0 or -2 (P > 0.10). In the spring, a decreased MAX_T
      was associated with CALFD. Maximum environmental temperatures on d 0 (14.7 vs.
      16.0 degrees C), -1 (14.4 vs. 16.0 degrees C), and -3 (14.0 vs. 15.7 degrees C)
      were less for CALFD compared with NOCALFD (P < 0.05). No difference was detected
      on d -2 (P > 0.10). For fall, MIN_T was greater on d -1 (12.8 vs. 11.3 degrees
      C), -2 (13.0 vs. 11.4 degrees C), and -3 (13.1 vs. 11.7 degrees C) for CALFD
      compared with NOCALFD (P < 0.05). In spring, MIN_T for d 0 (2.6 vs. 3.9 degrees
      C), -1 (2.5 vs. 3.7 degrees C), -2 (2.1 vs. 3.7 degrees C), and -3 (1.8 vs. 3.8
      degrees C) were lesser (P < 0.05) for CALFD vs. NOCALFD. These data indicate that
      for spring-calving cows, a greater BARO and decreased MAX_T and MIN_T were
      associated with CALFD, whereas for fall-calving cows, an increase in MAX_T and
      MIN_T was associated with CALFD. Therefore, monitoring weather conditions may
      assist producers in preparing for the obstetric assistance of beef cattle.

PMID- 22147488
TI  - Determination and prediction of digestible and metabolizable energy from chemical
      analysis of corn coproducts fed to finishing pigs.
AB  - Twenty corn coproducts from various wet- and dry-grind ethanol plants were fed to
      finishing pigs to determine DE and ME and to generate equations predicting DE and
      ME based on chemical analysis. A basal diet comprised corn (97.05%), limestone,
      dicalcium phosphate, salt, vitamins, and trace minerals. Twenty test diets were
      formulated by mixing the basal diet with 30% of a coproduct, except for dried
      corn solubles and corn oil, which were included at 20 and 10%, respectively.
      There were 8 groups of 24 finishing gilts (n = 192; BW = 112.7 +/- 7.9 kg).
      Within each group, gilts were randomly assigned to 1 of 5 test diets or the basal
      diet for a total of 4 replications per diet per group. Two groups of gilts were
      used for each set of coproducts, resulting in 8 replications per coproduct and 32
      replications of the basal diet. The experiment was conducted as a completely
      randomized design. Gilts were placed in metabolism crates and offered 3 kg daily
      of their assigned test diet for 13 d, with total collection of feces and urine
      during the last 4 d. Ingredients were analyzed for DM, GE, CP, ether extract,
      crude fiber, NDF, ADF, total dietary fiber (TDF), ash, AA, and minerals, and in
      vitro OM digestibility was calculated for each ingredient. The GE was determined
      in the diets, feces, and urine to calculate DE and ME for each ingredient. The DE
      and ME of the basal diet were used as covariates among groups of pigs. The DE of
      the coproducts ranged from 2,517 kcal/kg of DM (corn gluten feed) to 8,988
      kcal/kg of DM (corn oil), and ME ranged from 2,334 kcal/kg of DM (corn gluten
      feed) to 8,755 kcal/kg of DM (corn oil). By excluding corn oil and corn starch
      from the stepwise regression analysis, a series of DE and ME prediction equations
      were generated. The best fit equations were as follows: DE, kcal/kg of DM = 
      7,471 + (1.94 * GE) - (50.91 * ether extract) + (15.20 * total starch) + (18.04 *
      OM digestibility), with R(2) = 0.90, SE = 227, and P < 0.01; ME, kcal/kg of DM =
      (0.90 * GE) - (29.95 * TDF), with R(2) = 0.72, SE = 323, and P < 0.01. Additional
      equations for DE and ME included NDF in the instance that TDF data were not
      available. These results indicate that DE and ME varied substantially among corn
      coproducts and that various nutritional components can be used to accurately
      predict DE and ME in corn coproducts for finishing pigs.

PMID- 22147489
TI  - Concentration of pro-vitamin A carotenoids in common beef cattle feedstuffs.
AB  - Quantification of the pro-vitamin A carotenoids in feedstuffs commonly fed to
      livestock has been ignored for many years. A greater dietary concentration of
      vitamin A has the potential to limit adipogenesis in cattle, thereby reducing
      carcass quality and value. A survey of 18 feedstuffs commonly fed to beef cattle
      was conducted for determination of vitamin A equivalents based on analysis of
      carotenoids. The pro-vitamin A carotenoids of interest were beta-carotene, alpha
      carotene, and beta-cryptoxanthin. Collaborators in 5 states collected the
      feedstuffs and then shipped them to The Ohio State University for compilation and
      analysis. Carotenoids were extracted from the feedstuffs and then quantified
      using HPLC with photodiode array analysis. Fresh fescue pasture contained
      approximately 10 times more vitamin A equivalents than hay and 5 times more than
      corn silage (39,865, 2,750, and 6,900 IU of vitamin A/kg of DM for fresh pasture,
      hay, and corn silage, respectively). Beta-cryptoxanthin and alpha-carotene could
      not be detected in any forage samples. Hay and corn silage vitamin A equivalents
      decreased over extended periods of time from harvest to sample collection. Corn
      was the only feedstuff to have appreciable concentrations of all 3 pro-vitamin A
      carotenoids quantified. Corn processing had a minimal impact on the vitamin A
      equivalents. High-moisture corn contained 54% more vitamin A equivalents than
      whole shelled corn (378 and 174 IU of vitamin A/kg of DM, respectively). Pro
      vitamin A carotenoids were more concentrated in corn coproducts than in whole
      shelled corn. The drying of distillers grains with solubles may significantly
      degrade beta-carotene (800 and 480 IU/kg of DM for wet and dry distillers grains,
      respectively). Soybean-based feedstuffs contain a small concentration of pro
      vitamin A carotenoids, at 55 and 45 IU of vitamin A/kg of DM for soybean meal and
      soybean hulls, respectively. Overall, there was considerable variation in the pro
      vitamin A content of feedstuffs based on location and storage conditions. An
      extensive analysis of feedstuffs would need to be conducted for an accurate
      estimation of the vitamin A content of feedlot cattle diets.

PMID- 22147490
TI  - Calreticulin mediates nerve growth factor-induced neuronal differentiation.
AB  - The nerve growth factor (NGF)/TrkA-signaling is necessary for neural development,
      and its abnormality has been tightly associated with the tumorigenesis of various
      cancers originated from the nervous system. The characterization of key molecules
      involved in the NGF/TrkA-mediated neuronal differentiation could pave the way for
      the development of novel therapeutic strategies against neural malignancy. We
      have previously demonstrated that calreticulin (CRT) is a favorable prognostic
      factor highly expressed in primary neuroblastomas (NBs) with a more
      differentiated histology. In the present study, we found that the level of CRT
      was enhanced in NGF-stimulated differentiation of PC-12 cells through the
      extracellular signal-regulated kinase (ERK)-dependent mitogen-activated protein
      kinase (MAPK) pathway. A deficiency of CRT significantly decreased NGF-elicited
      neuronal differentiation. Furthermore, overexpression of CRT enhanced neuronal
      differentiation via simultaneously activating the ERK-dependent MAPK pathway. The
      Ca(2+)-regulating capacity of CRT was demonstrated to be indispensable for NGF
      elicited neuronal differentiation. Intriguingly, the expression levels of CRT and
      NGF receptor TrkA were highly correlated in NBs with differentiated histology,
      and the coexistence of CRT and TrkA in NB tumors synergistically predicted a
      better 5-year survival rate. Together, our present findings delineate a CRT
      dependent regulation of NGF-induced neuronal differentiation.

PMID- 22147491
TI  - Raman spectroscopy as a detection and analysis tool for in vitro specific
      targeting of pancreatic cancer cells by EGF-conjugated, single-walled carbon
      nanotubes.
AB  - Single-walled carbon nanotubes (SWCNTs) were covalently linked to epidermal
      growth factor (EGF) proteins through an esterification process that was found to
      be responsible for the docking of SWCNTs on the human pancreatic cancer cells
      (PANC-1) surface, thus providing a mechanism for the enhanced delivery and
      internalization of the nanotubes. Micro Raman spectroscopy and enzyme-linked
      immunosorbent assay were used to evaluate the delivery process and kinetics of
      the SWCNTs. In vitro studies indicated that the delivery kinetics of SWCNT-EGF
      conjugates, at a concentration of 85 ug ml(-1), to the PANC-1 cell surfaces was
      significant in the first 30 min of incubation, but reached a plateau with time in
      accordance with the establishment of equilibrium between the association and the
      dissociation of EGF with the cell receptors. SWCNT-EGF conjugates could act as
      strong thermal ablation agents and could induce higher percentages of cellular
      death compared with the nontargeted SWCNTs alone.

PMID- 22147492
TI  - Genetic drift. The diagnostic odyssey to Rett syndrome: the experience of an
      Australian family.

PMID- 22147493
TI  - Studies of methylhexaneamine in supplements and geranium oil.
AB  - A number of supplements are now available which are sold as fat burners or pre
      workout boosters and contain stimulants which are banned in sport. Many contain
      methylhexaneamine under one of many pseudonyms including Geranamine, geranium oil
      or extract, or a number of chemical names such as 1,3-dimethylpentylamine. This
      has resulted in many athletes returning an adverse finding and having sanctions
      imposed. Other stimulants such as caffeine, phenpromethamine, synefrine, and
      phenethylamines are also to be found in supplements. This communication shows
      that geranium oils do not contain methylhexaneamine and that products labelled as
      containing geranium oil but which contain methylhexaneamine can only arise from
      the addition of synthetic material. Since the usual dose of methylhexaneamine is
      large, the drug is excreted at relatively high amounts for more than 29 h, the
      time for which the excretion was studied.

PMID- 22147494
TI  - Vicarious exposure to trauma and growth in therapists: the moderating effects of
      sense of coherence, organizational support, and empathy.
AB  - Therapists who work with traumatized individuals can experience psychological
      growth following this vicarious exposure to trauma. The purpose of the present
      study is to examine the variables that may moderate such vicarious posttraumatic
      growth. Therapists (N = 118) completed measures of vicarious exposure to trauma
      and growth, as well as empathy, sense of coherence, and perceived organizational
      support. Results showed that having a strong sense of coherence negatively
      predicted growth (beta = -.28, p = .001), whereas empathy was a positive
      predictor (beta = .37, p < .001). Empathy also moderated the exposure to growth
      relationship when growth involved relating to others (beta = -.20; p = .018).
      Organizational support did not predict growth. The results have implications for
      the recruitment, training, and supervision of therapists working with individuals
      who have experienced trauma.

PMID- 22147495
TI  - Natively unfolded state for engineering nanoscale fibrillar arrays.
AB  - A generic rationale for the fabrication of high aspect ratio fibrillar nanoscale
      arrays is described. The design emulates an intermittence effect observed for
      beta-structured alpha-synunclein fibrils, reported herein, in a structurally
      unrelated alpha-helical fiber. The generated nanoarrays are composed of periodic
      nanosized segments separated at uniform distances of unfolded regions. These
      regions can be targeted for conformational binding and refolding with metal
      nanoparticle-peptide conjugates for the conversion of fibrillar arrays into
      nanoparticle arrays. The introduced concept opens new strategies for engineering
      novel nanoscale materials and devices.

PMID- 22147496
TI  - Intermittent supplementation with rapamycin as a dietary restriction mimetic.

PMID- 22147497
TI  - Internet and electronic resources for inflammatory bowel disease: a primer for
      providers and patients.
AB  - Patients with inflammatory bowel disease (IBD) are increasingly turning to the
      Internet to research their condition and engage in discourse on their
      experiences. This has resulted in new dynamics in the relationship between
      providers and their patients, with misinformation and advertising potentially
      presenting barriers to the cooperative patient-provider partnership. This article
      addresses important issues of online IBD-related health information and social
      media activity, such as quality, reliability, objectivity, and privacy. We
      reviewed the medical literature on the quality of online information provided to
      IBD patients, and summarized the most commonly accessed Websites related to IBD.
      We also assessed the activity on popular social media sites (such as Facebook,
      Twitter, and YouTube), and evaluated currently available applications for use by
      IBD patients and providers on mobile phones and tablets. Through our review of
      the literature and currently available resources, we developed a list of
      recommended online resources to strengthen patient participation in their care by
      providing reliable, comprehensive educational material.

PMID- 22147498
TI  - Interplay between defect structure and catalytic activity in the Mo(10-x)V(x)O(y)
      mixed-oxide system.
AB  - The Mo(10-x)V(x)O(y) solid-solution systems (0<=x<=10) were studied by electron
      paramagnetic resonance spectroscopy. The results show the existence of
      paramagnetic vanadyl VO(2+) species, whose concentration becomes maximal for
      Mo(5)V(5)O(y.). A quantitative analysis of the [VO(2+)] concentration as a
      function of the Mo/V ratio allows it to characterize the prevailing defect
      chemistry in the Mo(10-x)V(x)O(y) system. In this respect, the semi-conducting
      properties of Mo(10-x)V(x)O(y) are p-type in an interval of Mo(9)V(1)O(y)
      Mo(5)V(5)O(y) and switch into n-type because of the conduction electrons in a
      composition range of Mo(5)V(5)O(y)-Mo(1)V(9)O(y). Highest catalytic activity is
      obtained when vanadium acts as an acceptor center and oxygen vacancies nu(..)(O)
      are formed for reasons of charge compensation. In addition to the surface,
      nu(..)(O) and VO(2+) centers in the bulk have to be considered too for
      heterogeneous catalysis.

PMID- 22147500
TI  - Synthesis and biological evaluation of new Tetra-aza macrocyclic scaffold
      constrained oxadiazole, thiadiazole and triazole rings.
AB  - A new series of N,N'-(benzene-1,3-diyldi-1,3,4-oxadiazole-5,2-diyl)bis{2-[(5
      benzene-1,3-diyl-1,3,4-oxadiazol-2-yl)amino]acetamide}(macrocycle 1), N,N'
      (benzene-1,3-diyldi-1,3,4-thiadiazole-5,2-diyl)bis{2-[(5-benzene-1,3-diyl-1,3,4
      thiadiazol-2-yl)amino]acetamide} (macrocycle 2) and S,S'-[benzene-1,3-diylbis(4H
      1,2,4-triazole-5,3-diyl)]bis{[(5-benzene-1,3-diyl-4H-1,2,4-triazol-3
      yl)sulfanyl]ethanethioate}(macrocycle 3) was synthesized from isophthalic
      dihydrazide (4) through a multistep reaction sequence. All the synthesized
      compounds were screened for their inhibitory effect against four different
      bacterial strains: P. aeruginosa ATCC-20852, K. pneumoniae MTCC-618, S. aureus
      ATCC- 29737, S. typhi MTCC- 3214. The synthesized compounds showed a significant
      zone of inhibition and the results were comparable with that of the standard drug
      ciprofloxacin. The synthesized compounds were further studied for their possible
      in vitro antioxidant effects by DPPH scavenging, total antioxidant capacity,
      total reductive capacity and H(2) O(2)  scavenging activity. The results
      indicated that the in vitro antioxidant activity for all the three molecules was
      efficient when compared to the standards. The DNA interaction behavior of
      macrocycles 1-3 with CT-DNA was investigated by the absorption spectra obtained
      (K(b)  constant for 1 is 4.53 * 10(4)  M(-1) , for 2 is 5.75 * 10(4)  M(-1)  and
      for 3 is 5.86 * 10(4)  M(-1) ). Based on the results it can be interpreted that
      the reducing power effect of the newly synthesized compounds demonstrates a
      direct effect on DNA binding and hence inhibiting the bacterial growth through
      their action on DNA by inhibiting DNA replication or DNA transcription.

PMID- 22147501
TI  - Doxorubicin- and daunorubicin-induced regulation of Ca2+ and H+ fluxes through
      human bax inhibitor-1 reconstituted into membranes.
AB  - Bax inhibitor-1 (BI-1) is an evolutionarily conserved cell death suppressor in
      both animals and plants. We examined the effect of doxorubicin (DXR) and
      daunorubicin (DNR), which are clinically important anthracycline compounds, on
      the functional regulation of BI-1 reconstituted into membranes. DXR and DNR
      inhibited the proton-induced efflux of encapsulated Ca(2+) from membranes in a
      drug concentration-dependent manner. Both compounds also reduced the H(+) influx
      activity of BI-1. The proteoliposomes containing BI-1 increased the quenching of
      DXR fluorescence by Cu(2+), and the fluorescence energy transfer between pyrene
      labeled BI-1 and DXR was enhanced with increasing DXR concentrations. The
      dissociation constants and the number of binding sites for both drugs in BI-1
      were determined to be in the range of 3.7-4.5 * 10(-6) m and approximately 4-5/BI
      1 molecule, respectively, using a proteomicelle system. DXR also induced
      secondary structural changes in reconstituted BI-1 and abolished the ability of
      BI-1-overexpressing cells to protect against endoplasmic reticulum stress-induced
      cell death. However, when mitoxantrone was used instead of DNR and DXR as an
      anthracycline analog, no significant effects were observed. These results suggest
      that BI-1 can be considered to be a new cancer therapeutic target by
      anthracyclines because of its stimulatory effects in cancer/tumor progression.

PMID- 22147502
TI  - Genome-wide SNP genotyping identifies the Stereocilin (STRC) gene as a major
      contributor to pediatric bilateral sensorineural hearing impairment.
AB  - Hearing loss is the most prevalent sensory perception deficit in humans,
      affecting 1/500 newborns, can be syndromic or nonsyndromic and is genetically
      heterogeneous. Nearly 80% of inherited nonsyndromic bilateral sensorineural
      hearing loss (NBSNHI) is autosomal recessive. Although many causal genes have
      been identified, most are minor contributors, except for GJB2, which accounts for
      nearly 50% of all recessive cases of severe to profound congenital NBSNHI in some
      populations. More than 60% of children with a NBSNHI do not have an identifiable
      genetic cause. To identify genetic contributors, we genotyped 659 GJB2 mutation
      negative pediatric probands with NBSNHI and assayed for copy number variants
      (CNVs). After identifying 8 mild-moderate NBSNHI probands with a Chr15q15.3
      deletion encompassing the Stereocilin (STRC) gene amongst this cohort, sequencing
      of STRC was undertaken in these probands as well as 50 probands and 14 siblings
      with mild-moderate NBSNHI and 40 probands with moderately severe-profound NBSNHI
      who were GJB2 mutation negative. The existence of a STRC pseudogene that is 99.6%
      homologous to the STRC coding region has made the sequencing interpretation
      complicated. We identified 7/50 probands in the mild-moderate cohort to have
      biallelic alterations in STRC, not including the 8 previously identified
      deletions. We also identified 2/40 probands to have biallelic alterations in the
      moderately severe-profound NBSNHI cohort, notably no large deletions in
      combination with another variant were found in this cohort. The data suggest that
      STRC may be a common contributor to NBSNHI among GJB2 mutation negative probands,
      especially in those with mild to moderate hearing impairment.

PMID- 22147503
TI  - Inhibition of interferon response by cystatin B: implication in HIV replication
      of macrophage reservoirs.
AB  - Cystatin B and signal transducer and activator of transcription-1 (STAT-1)
      phosphorylation have recently been shown to increase human immunodeficiency virus
      1 (HIV-1) replication in monocyte-derived macrophages (MDM), but the molecular
      pathways by which they do are unknown. We hypothesized that cystatin B inhibits
      the interferon (IFN) response and regulates STAT-1 phosphorylation by interacting
      with additional proteins. To test if cystatin B inhibits the IFN-beta response,
      we performed luciferase reporter gene assays in Vero cells, which are IFN
      deficient. Interferon-stimulated response element (ISRE)-driven expression of
      firefly luciferase was significantly inhibited in Vero cells transfected with a
      cystatin B expression vector compared to cells transfected with an empty vector.
      To determine whether cystatin B interacts with other key players regulating STAT
      1 phosphorylation and HIV-1 replication, cystatin B was immunoprecipitated from
      HIV-1-infected MDM. The protein complex was analyzed by liquid chromatography
      tandem mass spectrometry. Protein interactions with cystatin B were verified by
      Western blots and immunofluorescence with confocal imaging. Our findings
      confirmed that cystatin B interacts with pyruvate kinase M2 isoform, a protein
      previously associated cocaine enhancement of HIV-1 replication, and major vault
      protein (MVP), an IFN-responsive protein that interferes with JAK/STAT signals.
      Western blot studies confirmed the interaction with pyruvate kinase M2 isoform
      and MVP. Immunofluorescence studies of HIV-1-infected MDM showed that upregulated
      MVP colocalized with STAT-1. To our knowledge, the current study is the first to
      demonstrate the coexpression of cystatin B, STAT-1, MVP, and pyruvate kinase M2
      isoform with HIV-1 replication in MDM and thus suggests novel targets for HIV-1
      restriction in macrophages, the principal reservoirs for HIV-1 in the central
      nervous system.

PMID- 22147504
TI  - A review of poisonous plants that cause reproductive failure and malformations in
      the ruminants of Brazil.
AB  - The objective of this review is to provide a report on toxic plants causing
      reproductive problems in ruminants in Brazil. Aspidosperma pyrifolium causes
      abortion or stillbirth in goats, as well as most likely in sheep and cattle, in
      the semiarid regions of Northeastern Brazil. Intoxications by Ateleia
      glazioveana, Tetrapterys acutifolia and T. multiglandulosa result in abortion and
      neonatal mortality in cattle and sheep, and the same signs have been
      experimentally observed in goats. These three plants can also cause cardiac
      fibrosis and a nervous disease with spongiosis of the central nervous system.
      Other plants known to cause abortion include Enterolobium contortisiliquum, E.
      gummiferum, Stryphnodendron coriaceum, S. obovatum and S. fissuratum. These
      plants can also cause digestive signs and photosensitization. Abortions have been
      reported in animals intoxicated by nitrates and nitrites as well. Infertility,
      abortions and the birth of weak offspring have been reported in animals
      intoxicated by plants containing swainsonine, including Ipomoea spp., Turbina
      cordata and Sida carpinifolia. Trifolium subterraneum causes estrogenism in
      cattle. Mimosa tenuiflora and, most likely, M. ophthalmocentra cause
      malformations and embryonic mortality in goats, sheep and cattle in the semiarid
      regions of Northeastern Brazil.

PMID- 22147505
TI  - Identification of ADH4 as a novel and potential prognostic marker in
      hepatocellular carcinoma.
AB  - Alcohol dehydrogenase 4 (ADH4) is an important member of ADH family that
      metabolize a wide variety of substrates including ethanol and retinol. Studies
      demonstrated that ADH4 was involved in cancer. Microarray data showed that the
      expression of ADH4 was reduced in hepatocellular carcinoma (HCC). However, the
      role of ADH4 in HCC carcinogenesis remains undefined. The aim of this study is to
      explore the clinical significance of ADH4 in progression and prognosis of HCC.
      The expression levels of ADH4 in 15 paired HCC and noncancerous (NC) liver
      tissues were measured by qRT-PCR and those in 4 paired samples by Western
      blotting. Another 91 paraffin-embedded HCC tissues were examined by
      immunohistochemistry. The qRT-PCR result showed that the expression level of ADH4
      mRNA in HCC was significantly lower than that in NC tissues (P<0.0001). Western
      blotting also displayed that ADH4 protein was notably reduced in HCC.
      Immunohistochemistry assay confirmed that ADH4 protein was remarkably reduced in
      59.3% HCC. The expression of ADH4 was correlated with the pathology grade
      (P=0.031) and serum AFP (P=0.022). HCC patients with lower ADH4 expression had
      much worse overall survival rate than that with high expression (P<0.001).
      Furthermore, multivariate analysis showed that ADH4 expression was an independent
      predictor of overall survival (HR, 0.154; 95%CI, 0.044-0.543; P=0.004). This is
      the first time that the expression levels of ADH4 mRNA and protein have found to
      be markedly reduced in HCC tissues and significantly associated with survival,
      suggesting that ADH4 is a novel and potential prognostic marker for HCC patients.

PMID- 22147506
TI  - Current and past cigarette smoking significantly increase risk for microscopic
      colitis.
AB  - BACKGROUND: Cigarette smoking is an important environmental factor affecting
      inflammatory bowel disease. The role of smoking has not been rigorously studied
      in microscopic colitis (MC). The aim of this study was to compare the association
      of cigarette smoking in individuals with MC compared to a control population
      without MC. METHODS: We reviewed the records of patients with a clinical and
      histologic diagnosis of collagenous colitis (CC) or lymphocytic colitis (LC).
      Clinical history, including alcohol and smoking status at the time of diagnosis
      of MC, were reviewed. In this case-control study, age- and gender-matched
      patients without diarrhea presenting for outpatient colonoscopy served as the
      control population. RESULTS: We analyzed a total of 340 patients with MC: 124
      with CC and 216 with LC. Overall, any smoking status (former or current) was
      associated with MC (odds ratio [OR] 2.12, 95% confidence interval [CI]: 1.56
      2.88). This risk was more prominent in current smokers (adjusted OR 5.36, 3.81,
      and 4.37 for CC, LC, and all MC, respectively, 95% CI all greater than 1). The
      association of smoking was not significantly affected by gender or average
      alcohol consumption. CONCLUSIONS: In our study population, cigarette smoking is a
      risk factor for the development of both forms of microscopic colitis. There were
      no significant differences between LC and CC, and current smoking and the
      development of microscopic colitis affected men and women similarly. We feel that
      these data are sufficient to discuss the potential risks of tobacco use in
      patients with microscopic colitis.

PMID- 22147508
TI  - Socioeconomic factors and total joint replacement: comment on the article by
      Mnatzaganian et al.

PMID- 22147509
TI  - Catalytic hydrogenation of carbon dioxide and bicarbonates with a well-defined
      cobalt dihydrogen complex.

PMID- 22147507
TI  - Characterization of a hierarchical network of hyaluronic acid/gelatin composite
      for use as a smart injectable biomaterial.
AB  - Hybrid HA/Ge hydrogel particles are embedded in a secondary HA network to improve
      their structural integrity. The internal microstructure of the particles is
      imaged through TEM. CSLM is used to identify the location of the Ge molecules in
      the microgels. Through indentation tests, the Young's modulus of the individual
      particles is found to be 22 +/- 2.5 kPa. The overall shear modulus of the
      composite is 75 +/- 15 Pa at 1 Hz. The mechanical properties of the substrate are
      found to be viable for cell adhesion. The particles' diameter at pH = 8 is twice
      that at pH = 5. The pH sensitivity is found to be appropriate for smart drug
      delivery. Based on their mechanical and structural properties, HA-Ge hierarchical
      materials may be well suited for use as injectable biomaterials for tissue
      reconstruction.

PMID- 22147510
TI  - Reasons to consider earlier treatment of chronic HBV infections.

PMID- 22147511
TI  - A ZEB1-HDAC pathway enters the epithelial to mesenchymal transition world in
      pancreatic cancer.

PMID- 22147512
TI  - Recruitment of histone deacetylases HDAC1 and HDAC2 by the transcriptional
      repressor ZEB1 downregulates E-cadherin expression in pancreatic cancer.
AB  - OBJECTIVE: Pancreatic cancer is characterised by invasive tumour spread and early
      metastasis formation. During epithelial-mesenchymal transition, loss of the cell
      adhesion molecule E-cadherin is frequent and can be caused by genetic or
      epigenetic modifications, recruitment of transcriptional activators/repressors or
      post-translational modifications. A study was undertaken to investigate how E
      cadherin expression in human pancreatic adenocarcinoma and pancreatic cancer cell
      lines is regulated. METHODS: In 25 human pancreatic cancer resection specimens,
      the coding region of the E-cadherin gene (CDH1) was sequenced for somatic
      mutations. The tumour samples and 11 established human pancreatic cancer cell
      lines were analysed by immunohistochemistry, western blot analysis, chromatin
      immunoprecipitation and methylation-specific PCR. The role of specific histone
      deacetylase inhibitors (HDACi) on pancreatic tumour cell migration and
      proliferation was studied in vitro. RESULTS: Neither somatic mutations nor CDH1
      promoter hypermethylation were found to be responsible for downregulation of E
      cadherin in pancreatic cancer. In the transcriptionally active CDH1 promoter,
      acetylation of histones H3 and H4 was detected whereas HDAC1 and HDAC2 were found
      attached only to a silent promoter. Expression of ZEB1, a transcription factor
      known to recruit HDACs, was seen in E-cadherin-deficient cell lines in which
      ZEB1/HDAC complexes were found attached to the CDH1 promoter. Moreover, knockdown
      of ZEB1 prevented HDAC from binding to the CDH1 promoter, resulting in histone
      acetylation and expression of E-cadherin. HDACi treatment attenuated tumour cell
      migration and proliferation. CONCLUSIONS: These findings imply an important role
      for histone deacetylation in the downregulation of E-cadherin in human pancreatic
      cancer. Recruitment of HDACs to the CDH1 promoter is regulated by the
      transcription factor ZEB1, and inhibition of HDACs may be a promising antitumour
      therapy for pancreatic cancer.

PMID- 22147513
TI  - The elegance of the gastric mucosal barrier: designed by nature for nature.

PMID- 22147514
TI  - Stimulating luteinizing hormone.
AB  - Low molecular weight luteinizing hormone (LMWLH) receptor agonists could be of
      interest as a potential doping substance for athletes. These orally active
      compounds induce the production of endogenous hormones such as testosterone in a
      similar way to LH. A method for the detection of these compounds needs to be
      direct as their effect--the excess production of endogenous hormones--cannot be
      proven by analysis techniques which test for endogenous hormones. In order to
      detect a broad range of potential LMWLH receptor agonists, a precursor ion
      monitoring liquid chromatography tandem mass spectrometry method was developed.
      The method was tested against a selection of urine samples to ascertain potential
      problems with background analytes interfering with the compounds of interests.
      Selected compounds were extracted with an established methodology from urine to
      determine suitability of implementing into general screening methodologies. The
      two available LMWLH receptor agonists could be detected at concentrations of 100
      ng/ml in urine samples. This establishes a basic precursor ion monitoring method
      suitable for screening purposes for the detection of LMWLH receptor agonists in
      urine samples.

PMID- 22147515
TI  - Free-standing arrays of isolated TiO2 nanotubes through supercritical fluid
      drying.
AB  - A common complication in fabricating arrays of TiO(2) nanotubes is that they
      agglomerate into tightly packed bundles during the inevitable solvent evaporation
      step. This problem is particularly acute for template-fabricated TiO(2)
      nanotubes, as the geometric tunability of this technique enables relatively large
      inter-pore spacings or, from another perspective, more space for lateral
      displacement. Our work showed that agglomeration results from the surface tension
      forces that are present as the ambient solvent is evaporated from the nanotube
      film. Herein, we report a processing and fabrication approach that utilizes
      supercritical fluid drying (CO(2)) to prepare arrays of template-fabricated
      TiO(2) nanotubes that are free-standing and spatially isolated. This approach
      could be beneficial to many emerging technologies, such as solid-state dye
      sensitized solar cells and vertically-oriented carbon nanotube electrodes.

PMID- 22147516
TI  - Phototropins but not cryptochromes mediate the blue light-specific promotion of
      stomatal conductance, while both enhance photosynthesis and transpiration under
      full sunlight.
AB  - Leaf epidermal peels of Arabidopsis (Arabidopsis thaliana) mutants lacking either
      phototropins 1 and 2 (phot1 and phot2) or cryptochromes 1 and 2 (cry1 and cry2)
      exposed to a background of red light show severely impaired stomatal opening
      responses to blue light. Since phot and cry are UV-A/blue light photoreceptors,
      they may be involved in the perception of the blue light-specific signal that
      induces the aperture of the stomatal pores. In leaf epidermal peels, the blue
      light-specific effect saturates at low irradiances; therefore, it is considered
      to operate mainly under the low irradiance of dawn, dusk, or deep canopies.
      Conversely, we show that both phot1 phot2 and cry1 cry2 have reduced stomatal
      conductance, transpiration, and photosynthesis, particularly under the high
      irradiance of full sunlight at midday. These mutants show compromised responses
      of stomatal conductance to irradiance. However, the effects of phot and cry on
      photosynthesis were largely nonstomatic. While the stomatal conductance phenotype
      of phot1 phot2 was blue light specific, cry1 cry2 showed reduced stomatal
      conductance not only in response to blue light, but also in response to red
      light. The levels of abscisic acid were elevated in cry1 cry2. We conclude that
      considering their effects at high irradiances cry and phot are critical for the
      control of transpiration and photosynthesis rates in the field. The effects of
      cry on stomatal conductance are largely indirect and involve the control of
      abscisic acid levels.

PMID- 22147518
TI  - MES16, a member of the methylesterase protein family, specifically demethylates
      fluorescent chlorophyll catabolites during chlorophyll breakdown in Arabidopsis.
AB  - During leaf senescence, chlorophyll (Chl) is broken down to nonfluorescent
      chlorophyll catabolites (NCCs). These arise from intermediary fluorescent
      chlorophyll catabolites (FCCs) by an acid-catalyzed isomerization inside the
      vacuole. The chemical structures of NCCs from Arabidopsis (Arabidopsis thaliana)
      indicate the presence of an enzyme activity that demethylates the C13(2)
      carboxymethyl group present at the isocyclic ring of Chl. Here, we identified
      this activity as methylesterase family member 16 (MES16; At4g16690). During
      senescence, mes16 leaves exhibited a strong ultraviolet-excitable fluorescence,
      which resulted from large amounts of different FCCs accumulating in the mutants.
      As confirmed by mass spectrometry, these FCCs had an intact carboxymethyl group,
      which slowed down their isomerization to respective NCCs. Like a homologous
      protein cloned from radish (Raphanus sativus) and named pheophorbidase, MES16
      catalyzed the demethylation of pheophorbide, an early intermediate of Chl
      breakdown, in vitro, but MES16 also demethylated an FCC. To determine the in vivo
      substrate of MES16, we analyzed pheophorbide a oxygenase1 (pao1), which is
      deficient in pheophorbide catabolism and accumulates pheophorbide in the
      chloroplast, and a mes16pao1 double mutant. In the pao1 background, we
      additionally mistargeted MES16 to the chloroplast. Normally, MES16 localizes to
      the cytosol, as shown by analysis of a MES16-green fluorescent protein fusion.
      Analysis of the accumulating pigments in these lines revealed that pheophorbide
      is only accessible for demethylation when MES16 is targeted to the chloroplast.
      Together, these data demonstrate that MES16 is an integral component of Chl
      breakdown in Arabidopsis and specifically demethylates Chl catabolites at the
      level of FCCs in the cytosol.

PMID- 22147517
TI  - Natural variation in Arabidopsis: from molecular genetics to ecological genomics.

PMID- 22147519
TI  - Silencing MPK4 in Nicotiana attenuata enhances photosynthesis and seed production
      but compromises abscisic acid-induced stomatal closure and guard cell-mediated
      resistance to Pseudomonas syringae pv tomato DC3000.
AB  - Mitogen-activated protein kinases (MAPKs) play pivotal roles in development and
      environmental interactions in eukaryotes. Here, we studied the function of a
      MAPK, NaMPK4, in the wild tobacco species Nicotiana attenuata. The NaMPK4
      silenced N. attenuata (irNaMPK4) attained somewhat smaller stature, delayed
      senescence, and greatly enhanced stomatal conductance and photosynthetic rate,
      especially during late developmental stages. All these changes were associated
      with highly increased seed production. Using leaf epidermal peels, we demonstrate
      that guard cell closure in irNaMPK4 was strongly impaired in response to abscisic
      acid and hydrogen peroxide, and consistently, irNaMPK4 plants transpired more
      water and wilted sooner than did wild-type plants when they were deprived of
      water. We show that NaMPK4 plays an important role in the guard cell-mediated
      defense against a surface-deposited bacterial pathogen, Pseudomonas syringae pv
      tomato (Pst) DC3000; in contrast, when bacteria directly entered leaves by
      pressure infiltration, NaMPK4 was found to be less important in the resistance to
      apoplast-located Pst DC3000. Moreover, we show that salicylic acid was not
      involved in the defense against PstDC3000 in wild-type and irNaMPK4 plants once
      it had entered leaf tissue. Finally, we provide evidence that NaMPK4 functions
      differently from AtMPK4 and AtMPK11 in Arabidopsis (Arabidopsis thaliana),
      despite their sequence similarities, suggesting a complex functional divergence
      of MAPKs in different plant lineages. This work highlights the multifaceted
      functions of NaMPK4 in guard cells and underscores its role in mediating various
      ecologically important traits.

PMID- 22147520
TI  - Next-generation systemic acquired resistance.
AB  - Systemic acquired resistance (SAR) is a plant immune response to pathogen attack.
      Recent evidence suggests that plant immunity involves regulation by chromatin
      remodeling and DNA methylation. We investigated whether SAR can be inherited
      epigenetically following disease pressure by Pseudomonas syringae pv tomato
      DC3000 (PstDC3000). Compared to progeny from control-treated Arabidopsis
      (Arabidopsis thaliana; C(1)), progeny from PstDC3000-inoculated Arabidopsis
      (P(1)) were primed to activate salicylic acid (SA)-inducible defense genes and
      were more resistant to the (hemi)biotrophic pathogens Hyaloperonospora
      arabidopsidis and PstDC3000. This transgenerational SAR was sustained over one
      stress-free generation, indicating an epigenetic basis of the phenomenon.
      Furthermore, P(1) progeny displayed reduced responsiveness of jasmonic acid (JA)
      inducible genes and enhanced susceptibility to the necrotrophic fungus Alternaria
      brassicicola. This shift in SA- and JA-dependent gene responsiveness was not
      associated with changes in corresponding hormone levels. Instead, chromatin
      immunoprecipitation analyses revealed that SA-inducible promoters of PATHOGENESIS
      RELATED GENE1, WRKY6, and WRKY53 in P(1) plants are enriched with acetylated
      histone H3 at lysine 9, a chromatin mark associated with a permissive state of
      transcription. Conversely, the JA-inducible promoter of PLANT DEFENSIN1.2 showed
      increased H3 triple methylation at lysine 27, a mark related to repressed gene
      transcription. P(1) progeny from the defense regulatory mutant non expressor of
      PR1 (npr1)-1 failed to develop transgenerational defense phenotypes,
      demonstrating a critical role for NPR1 in expression of transgenerational SAR.
      Furthermore, the drm1drm2cmt3 mutant that is affected in non-CpG DNA methylation
      mimicked the transgenerational SAR phenotype. Since PstDC3000 induces DNA
      hypomethylation in Arabidopsis, our results suggest that transgenerational SAR is
      transmitted by hypomethylated genes that direct priming of SA-dependent defenses
      in the following generations.

PMID- 22147522
TI  - Pneumatosis intestinalis after colonoscopy in a Crohn's disease patient with
      mucosal healing.

PMID- 22147521
TI  - Localization of cell wall polysaccharides in normal and compression wood of
      radiata pine: relationships with lignification and microfibril orientation.
AB  - The distribution of noncellulosic polysaccharides in cell walls of tracheids and
      xylem parenchyma cells in normal and compression wood of Pinus radiata, was
      examined to determine the relationships with lignification and cellulose
      microfibril orientation. Using fluorescence microscopy combined with
      immunocytochemistry, monoclonal antibodies were used to detect xyloglucan (LM15),
      beta(1,4)-galactan (LM5), heteroxylan (LM10 and LM11), and galactoglucomannan
      (LM21 and LM22). Lignin and crystalline cellulose were localized on the same
      sections used for immunocytochemistry by autofluorescence and polarized light
      microscopy, respectively. Changes in the distribution of noncellulosic
      polysaccharides between normal and compression wood were associated with changes
      in lignin distribution. Increased lignification of compression wood secondary
      walls was associated with novel deposition of beta(1,4)-galactan and with reduced
      amounts of xylan and mannan in the outer S2 (S2L) region of tracheids. Xylan and
      mannan were detected in all lignified xylem cell types (tracheids, ray tracheids,
      and thick-walled ray parenchyma) but were not detected in unlignified cell types
      (thin-walled ray parenchyma and resin canal parenchyma). Mannan was absent from
      the highly lignified compound middle lamella, but xylan occurred throughout the
      cell walls of tracheids. Using colocalization measurements, we confirmed that
      polysaccharides containing galactose, mannose, and xylose have consistent
      correlations with lignification. Low or unsubstituted xylans were localized in
      cell wall layers characterized by transverse cellulose microfibril orientation in
      both normal and compression wood tracheids. Our results support the theory that
      the assembly of wood cell walls, including lignification and microfibril
      orientation, may be mediated by changes in the amount and distribution of
      noncellulosic polysaccharides.

PMID- 22147523
TI  - Secreted amyloid precursor proteins promote proliferation and glial
      differentiation of adult hippocampal neural progenitor cells.
AB  - Amyloid precursor protein (APP) is an integral membrane glycoprotein present at
      high levels in nerve cells. Two soluble secreted forms, sAPPalpha and sAPPbeta,
      are processed from APP by two mutually exclusive proteolytic pathways. sAPPalpha
      shows a range of neuroprotective and growth factor properties, including
      reduction of neuronal injury and improvement in memory performance, in contrast
      to the generally less potent sAPPbeta. In addition, sAPPalpha has been shown to
      increase the proliferation of both embryonic neural stem cells and neural
      progenitor cells (NPCs) derived from the subventricular zone (SVZ) of the adult
      brain. However, an effect of sAPPalpha (or sAPPbeta) on adult hippocampal
      progenitor cell proliferation and differentiation has not previously been
      observed. In this study, we examined the effect of both the alpha- and beta
      cleaved ectodomains of sAPP on adult NPCs isolated from the subgranular zone
      (SGZ) of the rat hippocampus in the presence or absence of depolarizing
      conditions. Assays were performed to examine the effect of sAPPalpha and sAPPbeta
      on SGZ-derived adult NPC proliferation in parallel with SVZ-derived cells and on
      differentiation with SGZ-derived cells. We observed both sAPPalpha and sAPPbeta
      increased the proliferation of SGZ-derived NPCs in vitro. Further, treatment of
      SGZ-derived NPCs with either sAPPalpha or sAPPbeta increased the number of cells
      expressing the astrocytic marker GFAP and promoted cell survival. The effect on
      differential fate was observed in both the presence and absence of depolarizing
      conditions. Thus, both sAPPalpha and sAPPbeta exert a complex range of effects on
      SGZ-derived adult NPCs, including increasing NPC proliferation, maintaining cell
      viability, yet promoting glial over neuronal differentiation. These findings
      provide the first direct support for the secreted forms of APP regulating SGZ
      derived NPCs, and raise the possibility some or all of the effects may have
      therapeutic benefit in models of neurological disease.

PMID- 22147525
TI  - Ultrasound-assisted synthesis of novel alpha-aminophosphonates and their
      biological activity.
AB  - The synthesis of a series of novel alpha-aminosubstituted phosphonates was
      accomplished by the reaction of various substituted aldehydes with an amine
      amlodipine (3-ethyl 5-methyl (+/-)2-((2-aminoethoxy)methyl)-4-(2-chlorophenyl)-6
      methyl-1,4-dihydropyridene-3,5-dicarboxylate) followed by
      diethylphosphite/dibutylphosphite in ethanol using SnCl(2).2H(2)O as a Lewis acid
      catalyst, under conventional and ultrasonic irradiation. Their structures were
      established by analytical and spectral data. The title compounds showed good
      antibacterial, antifungal and antiviral activity depending on the nature of the
      bioactive groups at the alpha-carbon.

PMID- 22147524
TI  - Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-kappaB and NF
      kappaB-regulated gene products and induces death receptors leading to suppressed
      proliferation, induced chemosensitization, and suppressed osteoclastogenesis.
AB  - SCOPE: The incidence of cancer is significantly lower in regions where turmeric
      is heavily consumed. Whether lower cancer incidence is due to turmeric was
      investigated by examining its effects on tumor cell proliferation, on pro
      inflammatory transcription factors NF-kappaB and STAT3, and on associated gene
      products. METHODS AND RESULTS: Cell proliferation and cell cytotoxicity were
      measured by the MTT method, NF-kappaB activity by EMSA, protein expression by
      Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by
      TRAP assay. Turmeric inhibited NF-kappaB activation and down-regulated NF-kappaB
      regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1),
      proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The
      spice suppressed the activation of STAT3, and induced the death receptors (DR)4
      and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of
      tumor cell lines. Furthermore, turmeric sensitized the tumor cells to
      chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more
      potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF
      kappaB activation induced by RANKL that correlated with the suppression of
      osteoclastogenesis. CONCLUSION: Our results indicate that turmeric can
      effectively block the proliferation of tumor cells through the suppression of NF
      kappaB and STAT3 pathways.

PMID- 22147526
TI  - Mycolic acids as diagnostic markers for tuberculosis case detection in humans and
      drug efficacy in mice.
AB  - Mycolic acids are attractive diagnostic markers for tuberculosis (TB) infection
      because they are bacteria-derived, contain information about bacterial species,
      modulate host-pathogen interactions and are chemically inert. Here, we present a
      novel approach based on mass spectrometry. Quantification of specific precursor 
      > fragment transitions of approximately 2000 individual mycolic acids (MAs)
      resulted in high analytical sensitivity and specificity. We next used this tool
      in a retrospective case-control study of patients with pulmonary TB with varying
      disease burdens from South Korea, Vietnam, Uganda and South Africa. MAs were
      extracted from small volume sputum (200 ul) and analysed without the requirement
      for derivatization. Infected patients (70, 19 of whom were HIV+) could be
      separated from controls (40, 20 of whom were HIV+) with a sensitivity and
      specificity of 94 and 93%, respectively. Furthermore, we quantified MA species in
      lung tissue of TB-infected mice and demonstrated effective clearance of MA levels
      following curative rifampicin treatment. Thus, our results demonstrate for the
      first time the feasibility and clinical relevance of direct detection of
      mycobacterial lipids as biomarkers of TB infection.

PMID- 22147527
TI  - Formulation design and high-throughput excipient selection based on structural
      integrity and conformational stability of dilute and highly concentrated IgG1
      monoclonal antibody solutions.
AB  - A systematic approach is presented to characterize and stabilize the higher order
      structural integrity of an immunoglobulin G (IgG1) monoclonal antibody (mAb)
      formulated at both low concentrations and as a highly concentrated solution. The
      conformational and colloidal stabilities of a recombinant humanized IgG1kappa mAb
      at both 1 and 100 mg/mL were investigated as a function of solution temperature
      (10 degrees C-87.5 degrees C) and pH (3-8). Protein secondary structure was
      characterized using circular dichroism, whereas intrinsic (tryptophan) and
      extrinsic (8-anilino-1-naphthalenesulfonic acid) fluorescence spectroscopy
      measurements were used to evaluate the tertiary structure of the protein. Light
      scattering analysis was employed to monitor mAb aggregation behavior as a
      function of temperature and solution pH. These biophysical data sets were
      analyzed and summarized using a previously described empirical phase diagrams
      (EPDs) approach. The different phases observed in the EPD were correlated with
      the individual physical states of the IgG1 in solution (aggregated, native,
      unfolded, etc.). The temperature-dependent conformational stability profile of
      the mAb, at both 1 and 100 mg/mL, generally followed the order pH 6 >= pH 7 >= pH
      8 > pH 5 > pH 4 >= pH 3. Analysis of the EPD apparent phase boundaries identified
      solution conditions of pH 4.5 near 60 degrees C for the development of an
      excipient screening assay. A supplemented generally regarded as safe excipient
      library was screened using an aggregation assay (optical density at 350 nm) at
      low mAb concentrations (4 mg/mL) and potential stabilizers were identified. The
      ability of these excipients to prevent conformational alterations in high
      concentration mAb solutions (100 mg/mL) was determined by monitoring tertiary
      structure changes using an intrinsic fluorescence method. The results suggest
      that substantial increases in the onset temperature of thermal transitions (>5
      degrees C) are obtained in the presence of (a) 20% dextrose, (b) 20% sorbitol,
      and (c) 5% dextrose + 10% sorbitol. Similar stabilization effects were obtained
      at an intermediate (50 mg/mL) as well as low mAb concentrations (1 mg/mL).

PMID- 22147528
TI  - Social networking: implications for nurse educators.

PMID- 22147531
TI  - Guided self-organization: perception-action loops of embodied systems.

PMID- 22147532
TI  - Information processing in echo state networks at the edge of chaos.
AB  - We investigate information processing in randomly connected recurrent neural
      networks. It has been shown previously that the computational capabilities of
      these networks are maximized when the recurrent layer is close to the border
      between a stable and an unstable dynamics regime, the so called edge of chaos.
      The reasons, however, for this maximized performance are not completely
      understood. We adopt an information-theoretical framework and are for the first
      time able to quantify the computational capabilities between elements of these
      networks directly as they undergo the phase transition to chaos. Specifically, we
      present evidence that both information transfer and storage in the recurrent
      layer are maximized close to this phase transition, providing an explanation for
      why guiding the recurrent layer toward the edge of chaos is computationally
      useful. As a consequence, our study suggests self-organized ways of improving
      performance in recurrent neural networks, driven by input data. Moreover, the
      networks we study share important features with biological systems such as
      feedback connections and online computation on input streams. A key example is
      the cerebral cortex, which was shown to also operate close to the edge of chaos.
      Consequently, the behavior of model systems as studied here is likely to shed
      light on reasons why biological systems are tuned into this specific regime.

PMID- 22147533
TI  - Likelihood of attending to the color word modulates Stroop interference.
AB  - Three experiments investigated whether the Stroop color-naming effect is
      modulated by the likelihood of a color word capturing visual attention. In
      Experiment 1, a bar or a neutral word was presented at fixation as a color
      carrier, along with a color word randomly appearing in either an achromatic color
      (white in the main experiment, gray in a follow-up) or purple. Reduction of the
      Stroop effect (known as Stroop dilution) occurred when the color word was
      achromatic but not (or to a lesser extent) when it was in purple. In Experiment
      2, the color of the color word remained constant throughout trial blocks, and
      Stroop dilution was equally evident when the word was always in purple and when
      it was always in white. In Experiment 3, a color bar was presented as the color
      carrier with both a color word and a neutral word. In this case, the Stroop
      effect was larger when the color word appeared in purple, and smaller when the
      neutral word appeared in purple, than when neither word did. These results imply
      that the extent to which processing of a color word occurs is determined by the
      likelihood of the word capturing attention.

PMID- 22147534
TI  - On the advantage of being left-handed in volleyball: further evidence of the
      specificity of skilled visual perception.
AB  - High ball speeds and close distances between competitors require athletes in
      interactive sports to correctly anticipate an opponent's intentions in order to
      render appropriate reactions. Although it is considered crucial for successful
      performance, such skill appears impaired when athletes are confronted with a left
      handed opponent, possibly because of athletes' reduced perceptual familiarity
      with rarely encountered left-handed actions. To test this negative perceptual
      frequency effect hypothesis, we invited 18 skilled and 18 novice volleyball
      players to predict shot directions of left- and right-handed attacks in a video
      based visual anticipation task. In accordance with our predictions, and with
      recent reports on laterality differences in visual perception, the outcome of
      left-handed actions was significantly less accurately predicted than the outcome
      of right-handed attacks. In addition, this left-right bias was most distinct when
      predictions had to be based on preimpact (i.e., before hand-ball contact)
      kinematic cues, and skilled players were generally more affected by the
      opponents' handedness than were novices. The study's findings corroborate the
      assumption that skilled visual perception is attuned to more frequently
      encountered actions.

PMID- 22147535
TI  - Clinical outcomes in psoriatic arthritis: A systematic literature review.
AB  - OBJECTIVE: Many outcomes have been proposed in the assessment of psoriatic
      arthritis (PsA). The Outcome Measures in Rheumatology (OMERACT) core set for PsA
      evaluation comprises 6 domains: joints, skin, function, pain, patient's global
      assessment, and quality of life. The objective of this work was to assess
      reporting of outcomes in PsA, including patient-reported outcomes (PROs) in
      recent publications. METHODS: A systematic literature search of clinical trials
      related to PsA and reporting at least 1 clinical outcome between 2006 and 2010
      was performed in PubMed, i.e., just before to just after publication of the
      OMERACT core set. All clinical outcomes were noted and subdivided into domains of
      health. Data analysis was descriptive. RESULTS: Fifty-eight articles (12,405
      patients) were included in the analysis: 17 (29%) were randomized clinical
      trials; the patients' mean +/- SD age was 48.2 +/- 5.4 years and the mean +/- SD
      disease duration was 9.0 +/- 3.1 years. Eighty-four different outcomes were
      reported, with a mean +/- SD of 6.9 +/- 4.3 per study. Patients were mainly
      assessed using the 6 core set domains, reported in 37.9% (quality of life) to
      55.2% (skin) of articles; however, the core set was rarely completely reported
      since only 10.3% of the studies reported all 6 core domains. PROs were
      heterogeneous and in particular there was no consensus regarding the number of
      joints to assess and instruments for dactylitis and enthesitis. PROs were
      assessed in more than 75% of publications using 28 different instruments.
      CONCLUSION: There is great heterogeneity in PsA assessment, even since
      publication of the OMERACT core set. Better consensus on instruments to assess
      each domain of health and better insight into which outcomes are important for
      patients is needed.

PMID- 22147536
TI  - Amplification of anharmonicities in multiphoton vibrational action spectra.
AB  - The influence of one or several infrared laser pulses on the stability of bare
      and argon-tagged sodium chloride clusters is investigated theoretically by a
      combination of computational methods involving explicit molecular dynamics and
      properly calibrated unimolecular rate theories. The fragmentation spectra
      obtained by varying the laser frequency in the far-IR range is compared to the
      linear absorption spectrum resulting from the dipole moment autocorrelation
      function. Under appropriate laser field parameters, the action spectra are found
      to resemble the absorption spectra quite accurately in terms of positions, line
      widths, and even relative intensities. However, the action spectra exhibit
      residual and systematic redshifts of a few percent, which are partly due to the
      finite spectral bandwidth but are amplified by the progressive heating by the
      laser. A quantitative analysis suggests that these anharmonicity effects should
      generally arise upon multiple photon absorption.

PMID- 22147537
TI  - Hepatitis C virus-related cryoglobulinemic vasculitis: emerging trends in
      therapy.

PMID- 22147538
TI  - Synthesis and characterization of new fluorescent styrene-containing carborane
      derivatives: the singular quenching role of a phenyl substituent.
AB  - A set of neutral and anionic carborane derivatives in which the styrenyl fragment
      is introduced as a fluorophore group has been successfully synthesized and
      characterized. The reaction of the monolithium salts of 1-Ph-1,2-C(2)B(10)H(11),
      1-Me-1,2-C(2)B(10)H(11) and 1,2-C(2)B(10)H(12) with one equivalent of 4
      vinylbenzyl chloride leads to the formation of compounds 1-3, whereas the
      reaction of the dilithium salt of 1,2-C(2)B(10)H(12) with two equivalents of 4
      vinylbenzyl chloride gives disubstituted compound 4. The closo clusters were
      degraded using the classical method, KOH in EtOH, to afford the corresponding
      nido species, which were isolated as tetramethylammonium salts. The crystal
      structure of the four closo compounds 1-4 were analyzed by X-ray diffraction. All
      compounds, except 1, display emission properties, with quantum yields dependent
      on the nature of the cluster (closo or nido) and the substituent on the second
      C(cluster) atom. In general, closo compounds 2-4 exhibit high fluorescence
      emission, whereas the presence of a nido cluster produces a decrease of the
      emission intensity. The presence of a phenyl group bonded to the C(cluster)
      results in an excellent electron-acceptor unit that produces a quenching of the
      fluorescence. DFT calculations have confirmed the charge-separation state in 1 to
      explain the quenching of the fluorescence and the key role of the carboranyl
      fragment in this luminescent process.

PMID- 22147539
TI  - Toxic effects of cypermethrin on the male reproductive system: with emphasis on
      the androgen receptor.
AB  - The 15-day intact adult male assay was used to investigate the reproductive
      toxicity of cypermethrin. We also evaluated the contributions of the androgen
      receptor (AR) to cypermethrin-induced reproductive impairments. Sixty adult male
      Sprague-Dawley rats were randomly divided into five groups and treated with
      different doses of cypermethrin (0, 6.25, 12.5, 25 and 50 mg kg(-1) per day) by
      oral gavage for 15 days. After the rats were sacrificed, the testes,
      epididymides, seminal vesicles and prostates were excised and weighed. One testis
      was frozen to be used for daily sperm production. Another testis was processed
      for AR immunohistochemical analysis and electron microscopic observation. We
      found that the weights of prostates were significantly decreased in cypermethrin
      treatment at doses of 25 and 50 mg kg(-1) per day. Rats treated with cypermethrin
      at 50 mg kg(-1) per day exhibited a significant reduction in testicular daily
      sperm production. Seminiferous tubule changes were noted, including atrophy and
      distorted seminiferous tubules, reduction and deformation of spermatogonia,
      spermatocyte and disordered arrangement of spermatoblasts. Ultrastructural
      changes were found in cypermethrin-treated groups with disrupted cellular
      junctions, abnormal morphology of the nucleus, necrosis of spermatogonia
      spermatocytes and Sertoli cells. To clarify the possible mechanism, AR expression
      and the serum levels of testosterone were assayed. AR levels were significantly
      reduced in the rats treated with cypermethrin and the serum levels of
      testosterone were reduced in cypermethrin treatment at a dose of 50 mg kg(-1) per
      day. These data suggested that cypermethrin can induce impairments of the
      structure of seminiferous tubules and spermatogenesis in the male rats. The
      impairments can be attributed to the reduced AR expression.

PMID- 22147540
TI  - Wheat gliadins modified by deamidation are more efficient than native gliadins in
      inducing a Th2 response in Balb/c mice experimentally sensitized to wheat
      allergens.
AB  - SCOPE: Wheat gluten proteins such as gliadins constitute major food allergens.
      Gluten can be modified industrially by deamidation which increases its solubility
      and enhances its use as a food ingredient. Sensitization to deamidated gluten has
      been reported to cause severe allergic reactions with anaphylaxis. The aim of
      this study was therefore to compare the sensitization and elicitation potentials
      of native (NG) and deamidated (DG) gliadins. The reactivity pattern of mice IgE
      was also compared with that of DG-allergic patients. METHODS AND RESULTS: The
      ability of DG to sensitize Balb/c mice using intra-peritoneal administration with
      aluminium hydroxide as an adjuvant, and to elicit an allergic response after a
      challenge, was tested in comparison with NG. Mice sensitized with DG secreted
      higher levels of total IgE, IL-4, gliadin-specific IgE and IgG1 than mice
      sensitized with NG. By contrast, mice sensitized with NG produced higher levels
      of gliadin-specific IgG2a and INFgamma. After a challenge, histamine levels were
      higher in mice sensitised with DG. CONCLUSIONS: DG can sensitize mice much more
      efficiently than NG. Moreover, this mouse model of allergy to DG revealed an IgE
      reactivity pattern against purified gliadins which was very similar to that of DG
      allergic patients.

PMID- 22147541
TI  - Assessment of carotid stenosis using three-dimensional T2-weighted dark blood
      imaging: Initial experience.
AB  - PURPOSE: To evaluate the use of a T2-weighted SPACE sequence (T2w-SPACE) to
      assess carotid stenosis via several methods and compare its performance with
      contrast-enhanced magnetic resonance angiography (ceMRA). MATERIALS AND METHODS:
      Fifteen patients with carotid atherosclerosis underwent dark blood (DB)-MRI using
      a 3D turbo spin echo with variable flip angles sequence (T2w-SPACE) and ceMRA.
      Images were coregistered and evaluated by two observers. Comparisons were made
      for luminal diameter, luminal area, degree of luminal stenosis (NASCET: North
      American Symptomatic Endarterectomy Trial; ECST: European Carotid Surgery Trial,
      and area stenosis), and vessel wall area. Degree of NASCET stenosis was
      clinically classified as mild (<50%), moderate (50%-69%), or severe (>69%).
      RESULTS: Excellent agreement was seen between ceMRA and T2w-SPACE and between
      observers for assessment of lumen diameter, lumen area, vessel wall area, and
      degree of NASCET stenosis (r > 0.80, P < 0.001). ECST stenosis was consistently
      higher than NASCET stenosis (48 +/- 14% vs. 24 +/- 22%, P < 0.001). Area stenosis
      (72 +/- 2%) was significantly higher (P < 0.001) than both ESCT and NASCET
      stenosis. CONCLUSION: DB-MRI of carotid arteries using T2w-SPACE is clinically
      feasible. It provides accurate measurements of lumen size and degree of stenosis
      in comparison with ceMRA and offers a more reproducible measure of ECST stenosis
      than ceMRA.

PMID- 22147542
TI  - Differential risk of ulcerative colitis and Crohn's disease among boys and girls
      after cesarean delivery.

PMID- 22147543
TI  - Hattori chart based evaluation of body composition and its relation to body mass
      index in a group of Sri Lankan children.
AB  - OBJECTIVE: To assess the relationship between fat free mass (FFM), fat mass (FM),
      body mass index (BMI) and percentage fat mass (%FM) using Hattori chart in a
      group of Sri Lankan children. METHODS: In this cross sectional descriptive study
      involving 5-15 y old children, data from 4 different school surveys were pooled
      together. Height and weight were measured and BMI calculated. Total body water
      (TBW) was assessed using a height and weight based equation. Thus FFM and FM were
      assessed based on 2 C body composition model. Fat mass index (FMI) and Fat free
      mass index (FFMI) were calculated and plotted on Hattori chart. RESULTS: 4278
      individuals (1297 boys and 2981 girls) were studied. Individual values clearly
      showed that Sri Lankan children had a low FFMI and a high FMI. Individuals with
      similar BMI had their %FM distributed in a wide range. Even children categorized
      as wasted had high levels of %FM in their body. Mean FMI and FFMI for each age
      was plotted, and it showed that most of the weight gain is due to accumulation of
      fat in the body. CONCLUSIONS: This study shows that Sri Lankan children have a
      higher %FM from a younger age even when they are classified as wasted. As they
      grow older, the changes that occur in FM are more than FFM. This chart analysis
      clearly shows that BMI is not a good index to measure %FM in individuals of this
      population.

PMID- 22147544
TI  - Dicephalic parapagus conjoined twins.

PMID- 22147545
TI  - Epicormic ontogeny in Quercus petraea constrains the highly plausible control of
      epicormic sprouting by water and carbohydrates.
AB  - BACKGROUND AND AIMS: There is increasing evidence that suppressed bud burst and
      thus epicormic shoot emergence (sprouting) are controlled by water-carbohydrate
      supplies to entire trees and buds. This direct evidence is still lacking for oak.
      In other respects, recent studies focused on sessile oak, Quercus petraea, have
      confirmed the important constraints of sprouting by epicormic ontogeny. The main
      objective of this paper was thus to provide provisional confirmation of the water
      carbohydrate control and direct evidence of the ontogenic constraints by bringing
      together results already published in separate studies on water status and
      distribution of carbohydrates, and on accompanying vegetation and epicormics,
      which also quantify epicormic ontogeny. METHODS: This paper analyses results
      gained from a sessile oak experiment in which part of the site was free from
      fairly tall, dense accompanying vegetation. This experiment was initially focused
      on stand water status and more recently on the carbohydrate distribution of
      dominant trees. External observations of the epicormic composition and internal
      observations with X-ray computer tomography were undertaken on 60 and six trees,
      respectively. KEY RESULTS: Sprouting was more intense in the part of the stand
      free from accompanying vegetation and on upper trunk segments. A clear effect of
      epicormic ontogeny was demonstrated as well: the more epicormics a trunk segment
      bears, the more chances it had to bear sprouts. CONCLUSIONS: These results
      indirectly infer water-carbohydrate control and show direct evidence of
      constraints by epicormic ontogeny. These results have far-reaching consequences
      related to the quantification of all functions fulfilled by any type of epicormic
      structure in any part of the tree.

PMID- 22147546
TI  - Co-adaptation of seed dormancy and flowering time in the arable weed Capsella
      bursa-pastoris (shepherd's purse).
AB  - BACKGROUND AND AIMS: The duration of the plant life cycle is an important
      attribute that determines fitness and coexistence of weeds in arable fields. It
      depends on the timing of two key life-history traits: time from seed dispersal to
      germination and time from germination to flowering. These traits are components
      of the time to reproduction. Dormancy results in reduced and delayed germination,
      thus increasing time to reproduction. Genotypes in the arable seedbank
      predominantly have short time to flowering. Synergy between reduced seed dormancy
      and reduced flowering time would create stronger contrasts between genotypes,
      offering greater adaptation in-field. Therefore, we studied differences in seed
      dormancy between in-field flowering time genotypes of shepherd's purse. METHODS:
      Genotypes with early, intermediate or late flowering time were grown in a
      glasshouse to provide seed stock for germination tests. Secondary dormancy was
      assessed by comparing germination before and after dark-incubation. Dormancy was
      characterized separately for seed myxospermy heteromorphs, observed in each
      genotype. Seed carbon and nitrogen content and seed mass were determined as
      indicators of seed filling and resource partitioning associated with dormancy.
      KEY RESULTS: Although no differences were observed in primary dormancy, secondary
      dormancy was weaker among the seeds of early-flowering genotypes. On average,
      myxospermous seeds showed stronger secondary dormancy than non-myxospermous seeds
      in all genotypes. Seed filling was similar between the genotypes, but nitrogen
      partitioning was higher in early-flowering genotypes and in non-myxospermous
      seeds. CONCLUSIONS: In shepherd's purse, early flowering and reduced seed
      dormancy coincide and appear to be linked. The seed heteromorphism contributes to
      variation in dormancy. Three functional groups of seed dormancy were identified,
      varying in dormancy depth and nitrate response. One of these groups (FG-III) was
      distinct for early-flowering genotypes. The weaker secondary dormancy of early
      flowering genotypes confers a selective advantage in arable fields.

PMID- 22147547
TI  - Comparative studies of thermotolerance: different modes of heat acclimation
      between tolerant and intolerant aquatic plants of the genus Potamogeton.
AB  - BACKGROUND AND AIMS: Molecular-based studies of thermotolerance have rarely been
      performed on wild plants, although this trait is critical for summer survival.
      Here, we focused on thermotolerance and expression of heat shock transcription
      factor A2 (HSFA2) and its putative target gene (chloroplast-localized small heat
      shock protein, CP-sHSP) in two allied aquatic species of the genus Potamogeton
      (pondweeds) that differ in survival on land. METHODS: The degree of
      thermotolerance was examined using a chlorophyll bioassay to assess heat injury
      in plants cultivated under non- and heat-acclimation conditions. Potamogeton
      HSFA2 and CP-sHSP genes were identified and their heat-induction was quantified
      by real-time PCR. KEY RESULTS: The inhibition of chlorophyll accumulation after
      heat stress showed that Potamogeton malaianus had a higher basal thermotolerance
      and developed acquired thermotolerance, whereas Potamogeton perfoliatus was heat
      sensitive and unable to acquire thermotolerance. We found two duplicated HSFA2
      and CP-sHSP genes in each species. These genes were induced by heat shock in P.
      malaianus, while one HSFA2a gene was not induced in P. perfoliatus. In non-heat
      acclimated plants, transcript levels of HSFA2 and CP-sHSP were transiently
      elevated after heat shock. In heat-acclimated plants, transcripts were
      continuously induced during sublethal heat shock in P. malaianus, but not in P.
      perfoliatus. Instead, the minimum threshold temperature for heat induction of the
      CP-sHSP genes was elevated in P. perfoliatus. CONCLUSIONS: Our comparative study
      of thermotolerance showed that heat acclimation leads to species-specific changes
      in heat response. The development of acquired thermotolerance is beneficial for
      survival at extreme temperatures. However, the loss of acquired thermotolerance
      and plasticity in the minimum threshold temperature of heat response may be
      favourable for plants growing in moderate habitats with limited daily and
      seasonal temperature fluctuations.

PMID- 22147548
TI  - Synthesis and antioxidant properties of (3,4-dihydroxyphenyl)(2,3,4
      trihydroxyphenyl)methanone and its derivatives.
AB  - (3,4-Dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone (5) and its two
      derivatives with bromine were synthesized from reactions such as bromination and
      demethylation of (3,4-dimethoxyphenyl)(2,3,4-trimethoxyphenyl)methanone (6). The
      Wolf-Kishner reduction product (9) of 6 and its three derivatives with bromine
      were obtained. 4-(3,4-Dihydroxybenzyl)benzene-1,2,3-triol and its dibromide
      derivative (16) were also synthesized from 9 and the corresponding dibromide
      derivative. The in vitro antioxidant activities of nine new compounds synthesized
      in these reactions were determined by analyzing the radical scavenging activities
      of bromophenols for 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS),
      1,1-diphenyl-2-picryl-hydrazyl (DPPH), N,N-dimethyl-p-phenylenediamine (DMPD),
      and the superoxide anion radical (O(2)(.-)) and examining the total reducing
      power through Fe(3+)-Fe(2+) transformation, FRAP and CUPRAC assays and the
      ferrous ions (Fe(2+)) chelating activities. Moreover, the results of these
      activities were compared to those of standard antioxidant compounds such as
      butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol,
      and trolox. The results showed that the synthesized bromophenols had effective
      antioxidant power. The phenol 5 with two phenolic rings and five phenolic
      hydroxyl groups was the most potent antioxidant and radical scavenger. In
      conclusion, the new compounds are promising molecules to be used owing to their
      potential antioxidant properties.

PMID- 22147549
TI  - Antioxidants from barley husks impregnated in films of low-density polyethylene
      and their effect over lipid deterioration of frozen cod (Gadus morhua).
AB  - BACKGROUND: The changes in quality of cod fillets packaged in films with and
      without antioxidants during 12 months of frozen storage at - 20  degrees C were
      investigated in the present study. The following parameters were determined in
      order to study lipid hydrolysis and primary and secondary lipid oxidation in the
      samples during frozen storage: peroxide value, conjugated dienes, conjugated
      triene hydroperoxides, free fatty acids, totox value, thiobarbituric acid
      reactive substances and p-anisidine value. RESULTS: Films containing antioxidants
      isolated from barley husks were effective in slowing down lipid hydrolysis and
      primary and secondary lipid oxidation processes. Secondary lipid oxidation
      reached maximum values in the 12th month of storage in control samples and
      samples packaged with antioxidant-containing film. Maximum lipid hydrolysis and
      lipid oxidation values for control cod samples were significantly higher than the
      maximum values found in samples packaged with antioxidant-containing film.
      CONCLUSION: The results confirm the efficacy of natural antioxidants derived from
      barley husks in slowing down lipid hydrolysis and increasing the oxidative
      stability of cod flesh. They also demonstrate the potential usefulness of natural
      antioxidants extracted from barley husks in the development of active packaging
      films for food preservation.

PMID- 22147550
TI  - Spontaneous bacterial peritonitis: recent guidelines and beyond.

PMID- 22147551
TI  - Less stress, more success? Oncological implications of surgery-induced oxidative
      stress.
AB  - Reactive oxygen species (ROS) possess important cell signalling properties. This
      contradicts traditional thought which associated ROS activity with cell death.
      Emerging evidence clearly demonstrates that ROS signalling acts as a key
      regulator in tumour cell survival and in the cellular processes required for
      tumour cells to successfully metastasise and proliferate. The discovery of the
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) family of
      enzymes in the last decade has unravelled much of the mystery surrounding how ROS
      are generated. Tumour cells are now known to express Nox enzymes which produce
      ROS required for cellular signalling. Activation of Nox enzymes occurs via
      interaction with proinflammatory cytokines and growth factors, all of which are
      released following surgical trauma. As our understanding of the signalling
      capabilities of ROS grows, the oncological implications of ROS activity are
      gradually being revealed. Nox-derived ROS are known to play a central role in
      each step of the metastatic cascade including invasion, adhesion, angiogenesis
      and proliferation. This article describes how surgery creates a ROS-rich
      environment, which facilitates redox signalling, and also examines the role
      played by Nox enzymes in this process. The authors then explore current knowledge
      of the oncological implications of surgery-induced redox signalling, and discuss
      current and future therapeutic strategies targeted at ROS and Nox enzymes in
      cancer patients.

PMID- 22147552
TI  - Size evolution of gold nanoparticles in a millifluidic reactor.
AB  - The size evolution of gold nanoparticles in a millifluidic reactor is
      investigated using spatially resolved transmission electron microscopy (TEM). The
      experimental data is supported by numerical simulations, carried out to study the
      residence-time distribution (RTD) of tracers that have the same properties as Au
      ions. Size and size distribution of the particles within the channels are
      influenced by the mixing zones as well as the RTD. However, the Au nanoparticles
      obtained show a broader size distribution even at the shortest investigated
      residence time of 3.53 s, indicating that in addition to surface growth reaction
      kinetics also plays an important role. The comparison of time resolved particle
      growth within the millifluidic channel with flask-based reactions reveals that
      the particle size can be controlled better within millifluidic channels. Overall,
      the results indicate potential opportunities to utilize easy to fabricate
      millifluidic reactors for the synthesis of nanoparticles, as well as as for
      carrying out time resolved kinetic studies.

PMID- 22147554
TI  - Polyhedral magnetite nanocrystals with multiple facets: facile synthesis,
      structural modelling, magnetic properties and application for high capacity
      lithium storage.
AB  - Polyhedral magnetite nanocrystals with multiple facets were synthesised by a low
      temperature hydrothermal method. Atomistic simulation and calculations on surface
      attachment energy successfully predicted the polyhedral structure of magnetite
      nanocrystals with multiple facets. X-ray diffraction, field emission scanning
      electron microscopy, and high resolution transmission microscopy confirmed the
      crystal structure of magnetite, which is consistent with the theoretical
      modelling. The magnetic property measurements show the superspin glass state of
      the polyhedral nanocrystals, which could originate from the nanometer size of
      individual single crystals. When applied as an anode material in lithium ion
      cells, magnetite nanocrystals demonstrated an outstanding electrochemical
      performance with a high lithium storage capacity, a satisfactory cyclability, and
      an excellent high rate capacity.

PMID- 22147553
TI  - The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis.
AB  - Malignant astrocytomas are highly aggressive brain tumours with poor prognosis.
      While a number of structural genomic changes and dysregulation of signalling
      pathways in gliomas have been described, the identification of biomarkers and
      druggable targets remains an important task for novel diagnostic and therapeutic
      approaches. Here, we show that the Wnt-specific secretory protein Evi (also known
      as GPR177/Wntless/Sprinter) is overexpressed in astrocytic gliomas. Evi/Wls is a
      core Wnt signalling component and a specific regulator of pan-Wnt protein
      secretion, affecting both canonical and non-canonical signalling. We demonstrate
      that its depletion in glioma and glioma-derived stem-like cells led to decreased
      cell proliferation and apoptosis. Furthermore, Evi/Wls silencing in glioma cells
      reduced cell migration and the capacity to form tumours in vivo. We further show
      that Evi/Wls overexpression is sufficient to promote downstream Wnt signalling.
      Taken together, our study identifies Evi/Wls as an essential regulator of glioma
      tumourigenesis, identifying a pathway-specific protein trafficking factor as an
      oncogene and offering novel therapeutic options to interfere with the aberrant
      regulation of growth factors at the site of production.

PMID- 22147555
TI  - Interleukin-21 modulates Th1 and Th17 responses in giant cell arteritis.
AB  - OBJECTIVE: Giant cell arteritis (GCA) is a large-vessel vasculitis of unknown
      origin. Recent findings indicate that at least 2 separate lineages of CD4+ T
      cells, Th1 and Th17 cells, participate in vascular inflammation. The pathways
      driving these T cell differentiations are incompletely understood, but may
      provide novel therapeutic targets. This study was undertaken to identify
      cytokines involved in the pathogenesis of GCA. METHODS: Thirty GCA patients
      fulfilling the American College of Rheumatology criteria, with active disease or
      disease in remission, and 30 age-matched controls were included. Levels of 27
      cytokines were determined in culture supernatants, and flow cytometric analysis
      of peripheral blood mononuclear cells (PBMCs) and immunohistochemical analysis of
      temporal artery samples were performed. RESULTS: Multiparametric analysis of
      cytokines produced by PBMCs associated with GCA disease activity identified a
      signature involving interleukin-2 receptor (IL-2R), IL-12, interferon-gamma
      (IFNgamma), IL-17A, IL-21, and granulocyte-macrophage colony-stimulating factor
      (GM-CSF). An expansion of Th1 and Th17 cells and a decrease in Treg cells were
      observed in the peripheral blood of patients with active GCA. An expansion of IL
      21-producing CD4+ T cells was also observed in patients with active GCA and
      correlated positively with Th17 and Th1 cell expansion. Immunohistochemical
      analysis revealed IFNgamma, IL-17A, and IL-21 expression within inflammatory
      infiltrates. Stimulation of purified CD4+ T cells with IL-21 increased Th1 and
      Th17 cell frequencies and decreased FoxP3 expression. In contrast, blockade of IL
      21 using IL-21R-Fc markedly decreased the production of IL-17A and IFNgamma and
      increased FoxP3 expression. CONCLUSION: Our findings indicate that IL-21 plays a
      critical role in modulating Th1 and Th17 responses and Treg cells in GCA, and
      might represent a potential target for novel therapy.

PMID- 22147556
TI  - The role of inducible nitric oxide synthase and haem oxygenase 1 in growth and
      development of dental tissue'.
AB  - In this study, the activity of the antioxidant enzyme network was assessed
      spectrophotometrically in samples of dental pulp and dental papilla taken from
      third-molar gem extracts. The production of nitric oxide by the conversion of l
      (2,3,4,5)-[3H] arginine to l-(3H) citrulline, the activity of haem oxygenase 1
      (HO-1) through bilirubin synthesis and the expression of inducible nitric oxide
      synthase (iNOS), HO-1 proteins and messenger RNA by Western blot and reverse
      transcribed polymerase chain reaction were also tested. The objective of this
      study was to evaluate the role of two proteins, iNOS and HO-1, which are
      upregulated by a condition of oxidative stress present during dental tissue
      differentiation and development. This is fundamental for guaranteeing proper
      homeostasis favouring a physiological tissue growth. The results revealed an over
      expression of iNOS and HO-1 in the papilla, compared with that in the pulp,
      mediated by the nuclear factor kappa B transcription factor activated by the
      reactive oxygen species that acts as scavengers for the superoxide radicals. HO
      1, a metabolically active enzyme in the papilla, but not in the pulp, seems to
      inhibit the iNOS enzyme by a crosstalk between the two proteins. We suggest that
      the probable mechanism through which this happens is the interaction of HO-1 with
      haem, a cofactor dimer indispensible for iNOS, and the subsequent suppression of
      its metabolic activity.

PMID- 22147557
TI  - Acute effect of whey peptides upon blood pressure of hypertensive rats, and
      relationship with their angiotensin-converting enzyme inhibitory activity.
AB  - SCOPE: The aim of this study was to investigate the antihypertensive effect of a
      peptide fraction (PepC) obtained from a whey protein concentrate following
      hydrolysis by Cynara cardunculus, as well as of its fraction with MW below 3 kDa
      (PepCF). Both these concentrates encompassed peptides that exhibited potent in
      vitro inhibition of angiotensin-converting enzyme (ACE): two were released from
      alpha-lactalbumin--KGYGGVSLPEW and DKVGINYW, and one from beta-lactoglobulin-
      DAQSAPLRVY. METHODS AND RESULTS: Upon oral administration, by gastric intubation,
      of 400 mg/kg body weight (bw) of those peptide concentrates, or 5 mg/kg bw of the
      corresponding synthetic peptides, to 12 wk-old spontaneously hypertensive rats
      (SHR), the systolic and diastolic blood pressures were monitored by the tail-cuff
      method--before, and 2, 4, 6, 8 and 24 h afterwards. Water and zofenopril (5 mg/kg
      bw)--a known ACE-inhibitor, were used as negative and positive controls,
      respectively. Acute administration of PepC, PepCF, KGYGGVSLPEW, DKVGINYW and
      DAQSAPLRVY caused antihypertensive effects in SHR; the maximum effect occurred by
      4 h and 6 h after administration of the peptide concentrates and the synthetic
      peptides, respectively. PepC and KGYGGVSLPEW also showed ACE-inhibitory activity
      in vivo: the pressor effect of angiotensin I was significantly lower, and the
      response to bradykinin increased when the rats were pre-treated with either
      product. CONCLUSION: Our results strongly suggest that PepC will be effective as
      nutraceutical ingredient for the formulation of functional foods aimed at
      hypertension control.

PMID- 22147558
TI  - Cognitive control and the dopamine D2-like receptor: a dimensional understanding
      of addiction.
AB  - The phenotypic complexity of psychiatric conditions is revealed by the
      dimensional nature of these disorders, which consist of multiple behavioral,
      affective, and cognitive dysfunctions that can result in substantial psychosocial
      impairment. The high degree of heterogeneity in symptomatology and comorbidity
      suggests that simple categorical diagnoses of "affected" or "unaffected" may fail
      to capture the true characteristics of the disorder in a manner relevant to
      individualized treatment. A particular dimension of interest is cognitive control
      ability because impairments in the capacity to control thoughts, feelings, and
      actions are key to several psychiatric disorders. Here, we describe evidence
      suggesting that cognitive control over behavior is a crucial dimension of
      function relevant to addictions. Moreover, dopamine (DA) D(2)-receptor
      transmission is increasingly being identified as a point of convergence for these
      behavioral and cognitive processes. Consequently, we argue that measures of
      cognitive control and D(2) DA receptor function may be particularly informative
      markers of individual function and treatment response in addictions.

PMID- 22147559
TI  - In vivo proton electron double resonance imaging of mice with fast spin echo
      pulse sequence.
AB  - PURPOSE: To develop and evaluate a two-dimensional (2D) fast spin echo (FSE)
      pulse sequence for enhancing temporal resolution and reducing tissue heating for
      in vivo proton electron double resonance imaging (PEDRI) of mice. MATERIALS AND
      METHODS: A four-compartment phantom containing 2 mM TEMPONE was imaged at 20.1 mT
      using 2D FSE-PEDRI and regular gradient echo (GRE)-PEDRI pulse sequences. Control
      mice were infused with TEMPONE over ~1 min followed by time-course imaging using
      the 2D FSE-PEDRI sequence at intervals of 10-30 s between image acquisitions. The
      average signal intensity from the time-course images was analyzed using a first
      order kinetics model. RESULTS: Phantom experiments demonstrated that EPR power
      deposition can be greatly reduced using the FSE-PEDRI pulse sequence compared
      with the conventional gradient echo pulse sequence. High temporal resolution was
      achieved at ~4 s per image acquisition using the FSE-PEDRI sequence with a good
      image SNR in the range of 233-266 in the phantom study. The TEMPONE half-life
      measured in vivo was ~72 s. CONCLUSION: Thus, the FSE-PEDRI pulse sequence
      enables fast in vivo functional imaging of free radical probes in small animals
      greatly reducing EPR irradiation time with decreased power deposition and
      provides increased temporal resolution.

PMID- 22147561
TI  - 4H-1,4-benzothiazine, dihydro-1,4-benzothiazinones and 2-amino-5
      fluorobenzenethiol derivatives: design, synthesis and in vitro antimicrobial
      screening.
AB  - As part of our studies focused on the design and synthesis of new antimicrobial
      agents a series of 7-fluoro-3,4-dihydro-2H-1,4-benzothiazine derivatives (4a-4f,
      4h) and 7-fluoro-2H-1,4-benzothiazin-3(4H)-one analogues (4j-4o) were synthesized
      and evaluated for their in vitro inhibitory activity against a representative
      panel of Gram-positive and Gram-negative bacteria strains and also toward
      selected fungi species. These compounds were prepared in one step from chloro
      substituted-2-amino-5-fluorobenzenethiol 6a-6c. The biological screening
      identified in compounds 4a, 4j and 4l the most promising results of both series
      showing an interesting antimicrobial activity. Our antibiotic investigation was
      also completed by testing the key intermediates 6a-6c. Surprisingly, 6a-6c
      emerged as the compounds exhibiting the highest antimicrobial activity by
      possessing a remarkable antibacterial effect against the Gram-positive strains
      with MIC (minimal inhibitory concentration) values between 2 and 8 ug/mL and the
      fungi panel with MIC values between 2 and 8 ug/mL. These results may prove useful
      in the design of a novel pool of antimicrobial agents.

PMID- 22147560
TI  - OsHsfA2c and OsHsfB4b are involved in the transcriptional regulation of
      cytoplasmic OsClpB (Hsp100) gene in rice (Oryza sativa L.).
AB  - ClpB-cytoplasmic (ClpB-cyt)/Hsp100 is an important chaperone protein in rice.
      Cellular expression of OsClpB-cyt transcript is governed by heat stress, metal
      stress, and developmental cues. Transgenic rice plants produced with 2 kb OsClpB
      cyt promoter driving Gus reporter gene showed heat- and metal-regulated Gus
      expression in vegetative tissues and constitutive Gus expression in calli,
      flowering tissues, and embryonal half of seeds. Rice seedlings regenerated with
      OsClpB-cyt promoter fragment with deletion of its canonical heat shock element
      sequence (HSE(-273 to -280)) showed not only heat shock inducibility of Gus
      transcript/protein but also constitutive expression of Gus in vegetative tissues.
      It thus emerges that the only classical HSE present in OsClpB-cyt promoter is
      involved in repressing expression of OsClpB-cyt transcript under unstressed
      control conditions. Yeast one-hybrid assays suggested that OsHsfA2c specifically
      interacts with OsClpB-cyt promoter. OsHsfA2c also showed binding with OsClpB-cyt
      and OsHsfB4b showed binding with OsClpB-cyt; notably, interaction of OsHsfB4b was
      seen for all three OsClpB/Hsp100 protein isoforms (i.e., ClpB-cytoplasmic, ClpB
      mitochondrial, and ClpB-chloroplastic). Furthermore, OsHsfB4b showed interaction
      with OsHsfA2c. This study suggests that OsHsfA2c may play a role as
      transcriptional activator and that OsHsfB4b is an important part of this heat
      shock responsive circuitry.

PMID- 22147562
TI  - Direct versus hydrogen-assisted CO dissociation on the Fe (100) surface: a DFT
      study.
AB  - CO dissociation: Three most probable pathways to CO dissociation on the Fe (100)
      surface exist: a) direct, CO->C+O (-) and H-assisted b) H+CO<->HCO->CH+O (-) or
      c) CO+H<->COH->C+OH (-). Under high hydrogen pressure conditions and highly
      occupied surfaces the formation of HCO and subsequent dissociation to CH+O may at
      best compete with direct dissociation.

PMID- 22147563
TI  - Patient tolerance of awake, in-office laryngeal procedures: a multi-institutional
      perspective.
AB  - OBJECTIVES/HYPOTHESIS: An increasing number of laryngeal procedures are performed
      in the office. However, little is known about how well these procedures are
      tolerated and what factors determine success or failure. STUDY DESIGN:
      Prospectively collected patient and physician surveys from five surgeons at two
      institutions describe patient tolerance of awake, in-office laryngeal procedures
      (AIOLPs). METHODS: There were 154 procedures performed in a 6-month period,
      including vocal fold injection (VFI) (72%), laser treatment (19%), and transnasal
      esophagoscopy (3%). Average duration of procedure was 13 +/- 8 minutes. RESULTS:
      Patients reported an average of 37 of 100 on a discomfort scale, with 0
      representing no discomfort and 100 representing maximal discomfort. Ninety-three
      percent of patients would undergo another procedure, and 96% would recommend
      AIOLPs to other patients. Procedures were completed successfully in 92%. Most
      common surgeon-reported difficulties included copious secretions and uncontrolled
      gag reflex. Procedures that involved such difficulties had a significantly lower
      rate of procedure completion, 73% vs. 96%, P = .0001. High preprocedure anxiety
      did not adversely impact patient comfort or procedure completion rate. There was
      no difference in discomfort scores based on VFI approach or patient familiarity
      with AIOLPs. There was a significant difference in discomfort score between
      patients with successful first-approach VFI and those who required a change in
      VFI approach, 36.0 vs. 61.3, respectively, P = .003. The rate of requiring a
      second and third VFI approach was 4.6% and 2.8%, respectively. CONCLUSIONS: This
      study encompasses multiple diagnoses, procedures, VFI techniques, and methods of
      anesthesia. AIOLPs are exceptionally well tolerated by patients, resulting in
      extremely high completion and satisfaction rates.

PMID- 22147564
TI  - The inhibition of liposaccharide heptosyltransferase WaaC with multivalent
      glycosylated fullerenes: a new mode of glycosyltransferase inhibition.
AB  - L,D-Heptosides (L-glycero-D-manno-heptopyranoses) are found in important
      bacterial glycolipids such as lipopolysaccharide (LPS), the biosynthesis of which
      is targeted for the development of novel antibacterial agents. This work
      describes the synthesis of a series of fullerene hexa-adducts bearing 12 copies
      of peripheral sugars displaying the mannopyranose core structure of bacterial L,D
      heptoside. The multimers were assembled through an efficient copper-catalyzed
      alkyne-azide cycloaddition reaction as the final step. The final fullerene sugar
      balls were assayed as inhibitors of heptosyltransferase WaaC, the
      glycosyltransferase catalyzing the incorporation of the first L-heptose into LPS.
      Interestingly, the inhibition of the final molecules was found in the low
      micromolar range (IC(50) =7-45 MUM), whereas the corresponding monomeric
      glycosides displayed high micromolar to low millimolar inhibition levels (IC(50)
      always above 400 MUM). When evaluated on a "per-sugar" basis, these inhibition
      data showed that, in each case, the average affinity of a single glycoside of the
      fullerenes towards WaaC was significantly enhanced when displayed as a multimer,
      thus demonstrating an unexpected multivalent effect. To date, such a multivalent
      mode of inhibition had never been evidenced with glycosyltransferases.

PMID- 22147565
TI  - The application of structure-activity relationships to the prediction of the
      mutagenic activity of chemicals.
AB  - Prediction of mutagenicity by computer is now routinely used in research and by
      regulatory authorities. Broadly, two different approaches are in wide use. The
      first is based on statistical analysis of data to find patterns associated with
      mutagenic activity. The resultant models are generally termed quantitative
      structure-activity relationships (QSAR). The second is based on capturing human
      knowledge about the causes of mutagenicity and applying it in ways that mimic
      human reasoning. These systems are generally called knowledge-based system. Other
      methods for finding patterns in data, such as the application of neural networks,
      are in use but less widely so.

PMID- 22147566
TI  - Bacterial mutagenicity assays: test methods.
AB  - The most widely used assays for detecting chemically induced gene mutations are
      those employing bacteria. The plate incorporation assay using various Salmonella
      typhimurium LT2 and E. coli WP2 strains is a short-term bacterial reverse
      mutation assay specifically designed to detect a wide range of chemical
      substances capable of causing DNA damage leading to gene mutations. The test is
      used worldwide as an initial screen to determine the mutagenic potential of new
      chemicals and drugs.The test uses several strains of S. typhimurium which carry
      different mutations in various genes of the histidine operon, and E. coli which
      carry the same AT base pair at the critical mutation site within the trpE gene.
      These mutations act as hot spots for mutagens that cause DNA damage via different
      mechanisms. When these auxotrophic bacterial strains are grown on a minimal media
      agar plates containing a trace of the required amino-acid (histidine or
      tryptophan), only those bacteria that revert to amino-acid independence (His(+)
      or Tryp(+)) will grow to form visible colonies. The number of spontaneously
      induced revertant colonies per plate is relatively constant. However, when a
      mutagen is added to the plate, the number of revertant colonies per plate is
      increased, usually in a dose-related manner.This chapter provides detailed
      procedures for performing the test in the presence and absence of a metabolic
      activation system (S9-mix), including advice on specific assay variations and any
      technical problems.

PMID- 22147567
TI  - The mouse lymphoma assay.
AB  - The mouse lymphoma TK assay (MLA) is part of an in vitro battery of tests
      designed to predict risk assessment prior to in vivo testing. The test has the
      potential to detect mutagenic and clastogenic events at the thymidine kinase (tk)
      locus of L5178Y mouse lymphoma tk ( +/- ) cells by measuring resistance to the
      lethal nucleoside analogue triflurothymidine (TFT). Cells may be plated for
      viability and mutation in semi-solid agar (agar assay) or in 96-well microtitre
      plates (microwell assay). When added to selective medium containing TFT, wild
      type tk ( +/- ) cells die, but TFT cannot be incorporated into the DNA of mutant
      tk ( -/- ) cells, which survive to form colonies that may be large (indicative of
      gene mutation) or small (indicative of chromosomal mutation) in nature. Mutant
      frequency is expressed as the number of mutants per 10(6) viable cells.

PMID- 22147568
TI  - Mammalian cell HPRT gene mutation assay: test methods.
AB  - Using the combination of bacterial gene mutation assay and chromosomal
      aberrations test in mammalian cells may not detect a small proportion of
      mammalian specific mutagenic agents. Therefore, at the current time a third assay
      should be used, except for compounds for which there is little or no exposure
      (DOH (2000) Department of Health Guidance for the testing of chemicals for
      Mutagenicity. Committee on Mutagenicity of Chemicals in Food, Consumer Products
      and the Environment). The hypoxanthine phosphorybosyl transferase (HPRT) gene is
      on the X chromosome of mammalian cells, and it is used as a model gene to
      investigate gene mutations in mammalian cell lines. The assay can detect a wide
      range of chemicals capable of causing DNA damage that leads to gene mutation. The
      test follows a very similar methodology to the thymidine kinase (TK) mouse
      lymphoma assay (MLA), and both are included in the guidelines for mammalian gene
      mutation tests (OECD (1997) Organisation for Economic Co-operation and
      Development. Ninth addendum to the OECD Guidelines for the Testing of Chemicals.
      In Vitro Mammalian Cell Gene Mutation Test: 476). The HPRT methodology is such
      that mutations which destroy the functionality of the HPRT gene and or/protein
      are detected by positive selection using a toxic analogue, and HPRT ( - ) mutants
      are seen as viable colonies. Unlike bacterial reverse mutation assays, mammalian
      gene mutation assays respond to a broad spectrum of mutagens, since any mutation
      resulting in the ablation of gene expression/function produces a HPRT ( - )
      mutant. Human cells are readily used, and mechanistic studies using the HPRT test
      methodology with modifications, such as knock-out cell lines for DNA repair, can
      provide details of the mode of action (MOA) of the test compound (24).This
      chapter provides the methodology for carrying out the assay in different cell
      lines in the presence and absence of metabolism with technical information and
      general advice on how to carry out the test.

PMID- 22147569
TI  - The in vitro mammalian chromosome aberration test.
AB  - The short-term in vitro mammalian cell chromosome aberration test is used to
      assess potential genotoxic hazard of test substances. Mammalian cells are
      cultured in vitro, exposed to a test substance, harvested, and the frequency of
      asymmetrical structural chromosome aberrations is measured. Human peripheral
      blood lymphocytes do not normally divide. The assessment of the effects of
      cyclophosphamide on lymphocytes, stimulated to divide in whole blood cultures in
      vitro, is described. Procedures that are important in generating accurate results
      are emphasised, to avoid false positive results. The study design for a
      regulatory assay, the use of established cell lines, alternative methods of
      measuring cytotoxicity and analysis of results are included.

PMID- 22147570
TI  - The interpretation and analysis of cytogenetic data.
AB  - Chromosome aberration analysis has been the basis of one of core tests in genetic
      toxicology since guidelines were first established (DHSS (1981) Guidelines for
      the Testing of Chemicals for Mutagenicity. Prepared by the Committee on
      Mutagenicity of Chemcials in Food, Consumer Products, and the Environment,
      Department of Health and Social Security. Report on Health and Social Subjects,
      No. 24. Her Majesty's Stationery Office, London; IPCS (1985) Guide to short-term
      tests for detecting mutagenic and carcinogenic chemicals prepared for the IPCS by
      the International Commission for Protection against Environmental Mutagens and
      Carcinogens. Geneva, WHO). The technique consists of microscope examination of
      preparations of chromosomes, usually mammalian, for clastogenicity (chromosome
      breakage events), and agents which induce such changes are considered
      genotoxic.There are a number of different types of aberrations, and within types,
      considerable variation in their appearance. This chapter addresses aberration
      classification, their appearance, frequency and fate, and the range within
      aberration types, potential mis-classifications, and data recording and
      interpretation.

PMID- 22147571
TI  - The in vitro micronucleus assay.
AB  - The in vitro micronucleus test detects genotoxic damage in interphase cells. The
      in vitro micronucleus test provides an alterative to the chromosome aberration
      test, and because the in vitro micronucleus test examines cells at interphase,
      the assessment of micronuclei can be scored faster, as the analysis of damage is
      thought to be less subjective and is more amenable to automation.Micronuclei may
      be the result of aneugenic (whole chromosome) or clastogenic (chromosome
      breakage) damage. This chapter provides methods for mononucleate and binucleate
      micronucleus tests and the addition of centromeric labelling and a non
      disjunction assay to investigate any potential aneugenic mode of action.

PMID- 22147572
TI  - The in vitro and in vivo comet assays.
AB  - The strategy for testing for genotoxicity covers three main areas, namely gene
      mutation, chromosome aberration or breakage (clastogenicity), and chromosome loss
      or gain (aneuploidy). The current generalized strategy consists of assays capable
      of detecting all of these endpoints using in vitro assays such as the Ames test
      for detecting gene mutations in bacteria, the human peripheral lymphocyte
      chromosome aberration (CA) test for detecting clastogenicity, and the in vitro
      micronucleus test for clastogenicity and aneuploidy. The primary in vivo assay,
      and generally the only in vivo assay required, is the in vivo rodent bone marrow
      micronucleus assay. However, there are instances when these assays alone are
      inadequate and further testing is required, especially in vivo. Historically, the
      preferred second assay has been the rodent liver unscheduled DNA synthesis assay
      but recently this has been superseded by the rodent single cell gel
      electrophoresis or Comet assay. This assay has numerous advantages especially in
      vivo, where virtually any tissue can be examined. The status of the in vitro
      comet assay in regulatory testing is much less clear although a preliminary
      review of data from the assay has shown it to be more specific than other in
      vitro genotoxicity tests and less prone to false positives.Detailed here are
      general protocols for both the in vitro and in vivo comet assays which will form
      the basis of the pending OECD guideline for the assay.

PMID- 22147573
TI  - Assessment of DNA interstrand crosslinks using the modified alkaline comet assay.
AB  - The single cell gel electrophoresis (SCGE) assay, more commonly known as the
      comet assay, due to the "comet-like" appearance of the cells, was originally
      developed as a technique to measure the presence of DNA single-strand breaks. The
      assay is performed on single cells embedded in agar and placed in an electrical
      field at alkaline pH, so that fragments of negatively charged single-stranded DNA
      move through the gel toward the positively charged anode. Undamaged DNA moves
      relatively slowly, forming the head of the comet, while DNA fragmented due to the
      presence of single-strand breaks, moves more quickly giving the appearance of the
      tail. The extent of DNA migration is a measure of the DNA damage present. Since
      it was first developed, the comet assay has been adapted for measuring other
      types of DNA damage. The neutral comet assay has been employed for DNA double
      strand breaks, while techniques using DNA repair enzymes to cleave specific
      adducts, UvrABC for ultraviolet radiation induced adducts, for example, have also
      been described. Here, we describe a modified version of the comet assay for the
      measurement of interstrand crosslinks (ICLs). Interstrand crosslinking agents
      include the chemotherapeutic agents mitomycin C and cis-platin, psoralen plus UVA
      light (PUVA) used to treat hyperproliferative skin disorders and diepoxybutane, a
      metabolite of 1,3-butadiene used in industrial processes and an environmental
      pollutant. ICLs are a potent and cytotoxic form of DNA damage as they prevent DNA
      strand separation, thereby preventing DNA replication. Their removal requires
      several different DNA repair processes including translesion synthesis and
      homologous recombination. As ICLs prevent separation of the DNA strands, their
      presence results in less DNA migration in the comet assay. To successfully
      measure ICLs, it is necessary to incorporate a step that induces single-strand
      breaks (using a defined dose of ionizing radiation) that allows the crosslinked
      DNA to migrate.

PMID- 22147574
TI  - 32P-postlabelling for the sensitive detection of DNA adducts.
AB  - 32P-postlabelling is a technique originally described by Kurt Randerath and
      colleagues for the sensitive detection of damage produced in DNA by reactive
      chemicals or genotoxins. The procedure essentially entails the enzymatic
      digestion of DNA to nucleoside 3'-monophosphates which are then radioactively
      labelled using T4 polynucleotide kinase and [gamma(32)P]-adenosine triphosphate.
      Adducted nucleoside-3'-5'-bisphosphates are then separated from their normal
      counterparts by thin layer chromatography. Prior to the development of the assay,
      quantification of DNA adducts was confined to studies that utilised compounds
      synthesised to be isotopically labelled with tritium or carbon-14. As such, these
      studies were limited to specific and recognised genotoxins that could be
      administered only in the laboratory to cultures or animals. With (32)P
      postlabelling it was possible not only to determine DNA adduct induction by a
      relatively uncharacterised suspected carcinogen, but also following exposure to
      complex mixtures containing a multitude of known and unknown potential
      genotoxins. The small amount of DNA required to perform the (32)P-postlabelling
      assay also meant that human biomonitoring studies using readily obtainable
      tissues, such as lymphocytes, were possible. Using the standard (32)P
      postlabelling method, it is possible to detect a single DNA adduct in 10(7) to
      10(8) normal nucleotides. The subsequent development of several enhancement
      methods improved this detection rate to one adduct in 10(10) nucleotides. For
      these reasons, the (32)-postlabelling assay represents an extremely versatile and
      extremely sensitive method to detect and monitor DNA damage.

PMID- 22147575
TI  - Methods for the detection of DNA adducts.
AB  - The detection and characterisation of DNA adducts can provide mechanistic
      information on mode of action for genotoxic chemicals and in this context is
      vital for human risk assessments. Adducts are measured extensively in
      biomonitoring studies to examine exposure to environmental, dietary, and
      occupational chemicals and as biomarkers of efficacy for cancer chemotherapeutic
      drugs and chemopreventive agents. Methods used for adduct analysis must possess a
      certain degree of specificity and be sufficiently sensitive to detect lesions in
      the model system under investigation. A variety of techniques have been
      established for this purpose, which are capable of detecting and quantifying
      adducts in DNA isolated from animal or human tissues, cells, and biofluids as
      well as naked DNA from in vitro studies. These can be grouped as those involving
      (32)P-post-labelling, mass spectrometry, physical detection methods,
      immunological assays and radiolabelled compounds. Each approach presents
      different advantages and limitations and the most appropriate method depends on
      the type of sample, level of damage, and nature of the investigation as well as
      practical considerations. In this chapter, the basic principles of the most
      commonly used quantitative methods are described and their strengths and
      weaknesses discussed.

PMID- 22147576
TI  - The GADD45a-GFP GreenScreen HC assay.
AB  - Mutagens, clastogens, and aneugens cause increased expression of the human
      GADD45a gene. This has been exploited in the GreenScreen HC genotoxicity assay in
      which the gene's expression is linked to the expression of green fluorescent
      protein (GFP). The host for the reporter construct is the human lymphoblastoid
      cell line TK6. It was chosen for its growth as a cell suspension, which allows
      simple pipette transfers, and for its wild-type p53 competent status. P53 is
      required for proper GADD45a expression, and more generally for genome stability.
      TK6 is a karyotypically stable cell line.The GreenScreen assays were designed to
      facilitate screening, and this is reflected in its microplate format and low
      compound requirement. Protocols are available for testing with and without S9 as
      a source of exogenous metabolic activation. Data is collected either
      spectrophotometrically or by flow cytometry, and a simple spreadsheet converts
      raw data into dose-response curves, and provides a statistically significant
      positive or negative result. Extensive validation has demonstrated that in
      contrast to other in vitro mammalian genotoxicity assays, the GADD45a assays have
      both high sensitivity and specificity - they very rarely produce misleading
      positive results.

PMID- 22147577
TI  - Real-time reverse-transcription polymerase chain reaction: technical
      considerations for gene expression analysis.
AB  - The reverse transcription - polymerase chain reaction (RT-PCR) is a sensitive
      technique for the quantification of steady-state mRNA levels, particularly in
      samples with limited quantities of extracted RNA, or for analysis of low level
      transcripts. The procedure amplifies defined mRNA transcripts by taking advantage
      of retroviral enzymes with reverse transcriptase (RT) activity, coupled to PCR.
      The resultant PCR product concentration is directly proportional to the initial
      starting quantity of mRNA, therefore allowing quantification of gene expression
      by incorporation of a fluorescence detector for the appropriate amplicons. In
      this chapter, we describe a number of the most popular techniques for performing
      RT-PCR and detail the subsequent analysis methodologies required to interpret the
      resultant data in either a relative manner or through absolute quantification of
      gene expression levels.

PMID- 22147578
TI  - Cytogenetic in vivo assays in somatic cells.
AB  - Chromosome aberration assays are employed to detect the induction of chromosome
      breakage (clastogenesis) in somatic and germ cells by direct observation of the
      chromosomal damage during metaphase analysis, or by indirect observation of
      chromosomal fragments. Thus, various types of cytogenetic change can be detected
      such as structural chromosome aberrations (CA), sister chromatid exchanges (SCE),
      ploidy changes, and micronuclei. Following the induction of the chromosomal
      damage, most of the aberrations and abnormalities detected by these assays can be
      detrimental or even lethal to the cell. Their presence, however, indicates a
      potential to also induce more subtle and therefore transmissible chromosomal
      damage which survives cell division to produce heritable cytogenetic changes.
      Usually, induced cytogenetic damage is accompanied by other genotoxic damage such
      as gene mutations.

PMID- 22147579
TI  - Cytogenetic methods in human biomonitoring: principles and uses.
AB  - Cellular phenotypes can be applied as biomarkers to differentiate normal from
      abnormal biological -conditions. Several cytogenetic methods have been developed
      and allow the accurate detection of such phenotypic changes.Based on their
      mechanisms of formation, cellular phenotypes may be used either as biomarkers of
      exposure or as biomarkers of effect. Therefore, it is important that cytogenetic
      methods implemented in human biomonitoring should be based on a good knowledge of
      these mechanisms.In this chapter, we aim to review the mechanistic basis, the
      methodology, and the use in human biomonitoring studies of four major cytogenetic
      endpoints: sister chromatid exchanges (SCEs), high frequency cells (HFCs),
      chromosomal aberrations (CAs), and micronuclei (MN). In addition, an overview of
      potential confounding factors on the induction of these cytogenetic makers is
      presented. Furthermore, the combination of cytogenetics with molecular methods,
      which allows chromosome and gene identification on metaphase as well as in
      interphase cells with high resolution, is discussed. Finally, practical
      recommendations for an efficient application of these cytogenetic assays and a
      correct interpretation of the results on the basis of cellular phenotype(s)
      assessment in human biomonitoring are highlighted.

PMID- 22147580
TI  - The measurement of induced genetic change in mammalian germ cells.
AB  - In vivo methods are described to detect clastogenic and aneugenic effects of
      chemical agents in male and female germ cells in vivo. The knowledge of stages of
      germ cell development and their duration for a given test animal is essential for
      these experiments. Commonly, mice or rats are employed. Structural chromosome
      aberrations can be analyzed microscopically in mitotic cell divisions of
      differentiating spermatogonia, zygotes, or early embryos as well as in first
      meiotic cell divisions of spermatocytes and oocytes. Numerical chromosome
      aberrations are scorable during second meiotic divisions of spermatocytes and
      oocytes. The micronucleus test is applicable to early round spermatids and to
      first cleavage embryos, and as in somatic cells, it assesses structural as well
      as numerical chromosome aberrations. In contrast to the somatic micronucleus
      assay, the timing of cell sampling determines whether the micronuclei scored in
      round spermatids were formed from structural or numerical aberrations, i.e. with
      short treatment-sampling intervals the micronuclei are formed by exposed meiotic
      divisions and represent induced non-disjunction. On the -contrary, after longer
      intervals of 12-14 days micronuclei are formed from induced unstable structural
      aberrations in differentiating spermatogonia or during the last round of DNA
      synthesis in early spermatocytes. Furthermore, labelling with fluorescent DNA
      probes can be used to confirm these theoretical expectations. The mouse sperm
      FISH assay is totally based on scoring colour spots from individual chromosomes
      (e.g. X, Y, and 8) hybridized with specific DNA-probes. The most animal demanding
      assay described here is the dominant lethal test. It is commonly performed with
      treated male laboratory rodents and allows the determination of the most
      sensitive developmental stage of spermatogenesis to a particular chemical under
      test. Theoretically, unstable structural chromosome aberrations in sperm will
      lead to foetal deaths after fertilization at around the time of implantation in
      the uterus wall. These can be scored as deciduomata or early dead foetuses in the
      uterus wall of the females at mid-pregnancy. None of the tests described in this
      chapter provide data for a quantitative estimate of the genetic risk to progeny
      from exposed germ cells. The only tests on which such calculations can be based,
      the heritable translocation assay and the specific locus test, are so animal and
      time-consuming that they can no more be performed anywhere in the world and thus
      are not described here.

PMID- 22147581
TI  - Transgenic animal mutation models: a review of the models and how they function.
AB  - In regulatory genetic toxicology, the endpoints available for routine study in
      vivo have been limited to looking at chromosomal damage or unscheduled DNA
      synthesis in a very limited number of tissues. With the development of transgenic
      gene mutation systems in rodents came the opportunity to investigate a new
      endpoint. The better-known lambdaLacI and lambdaLacZ are covered in some detail
      and the less well established models do receive mention with appropriate
      references for those wishing more information. Using a recommended experimental
      design it is now possible to look at the ability of a compound to induce gene
      mutation following in vivo exposure, in any tissue from which suitable DNA can be
      isolated.

PMID- 22147582
TI  - Analysis of genotoxicity data in a regulatory context.
AB  - Analytical methods for regulatory tests usually must be defined before testing.
      To take this into account and to minimise equivocal interpretations, a sequential
      strategy is recommended. Assay validity must be verified and results then classed
      as clearly negative, clearly positive, or uncertain based on historical data.
      Where there is uncertainty, standard parametric or non-parametric statistical
      methods should be used with appropriate corrections to assess the significance.
      The biological importance of statistically significant data should then be
      evaluated using historical data.

PMID- 22147583
TI  - Isolation and purification of recombinant proteins, antibodies and plasmid DNA
      with hydroxyapatite chromatography.
AB  - Hydroxyapatite and related stationary phases increasingly play a role in the
      downstream processing of high-value biological materials, such as recombinant
      proteins, therapeutic antibodies and pharmaceutical-grade plasmid DNA.
      Chromatographic hydroxyapatite is an inorganic, ceramic material identical in
      composition, if not in structure, to calcium phosphate found in human bones and
      teeth. The interaction of hydroxyapatite with biomacromolecules is complex and
      highly dynamic, which can make predicting performance difficult, but also allows
      the design of very selective isolation processes. This review discusses the
      currently commercially available chromatographic materials, different retention
      mechanisms supported by these materials and differential exploitation for the
      design of highly specific isolation procedures. The state of the art of antibody
      purification by hydroxy- and fluoroapatite is reviewed together with tested
      routines for method development and implementation. Finally, the isolation of
      plasmid DNA is discussed, since the purification of DNA therapeutics at a
      sufficiently large scale is an emerging need in bioprocess development and
      perhaps the area in bioseparation where apatite chromatography can make its most
      important contribution to date.

PMID- 22147584
TI  - Importance of beta,beta-carotene 15,15'-monooxygenase 1 (BCMO1) and beta,beta
      carotene 9',10'-dioxygenase 2 (BCDO2) in nutrition and health.
AB  - In humans, varying amounts of absorbed beta-carotene are oxidatively cleaved by
      the enzyme beta,beta-carotene 15,15'-monooxygenase 1 (BCMO1) into two molecules
      of all-trans-retinal. The other carotenoid cleavage enzyme beta,beta-carotene
      9',10'-dioxygenase (BCDO2) cleaves beta-carotene at the 9',10' double bond
      forming beta-apo-10'-carotenal and beta-ionone. Although the contribution of
      BCDO2 to vitamin A formation has long been debated, BCMO1 is currently considered
      the key enzyme for retinoid metabolism. Furthermore, BCMO1 has limited enzyme
      activity towards carotenoids other than provitamin A carotenoids, whereas BCDO2
      exhibits a broader specificity. Both enzymes are located at different sites
      within the cell, with BCMO1 being a cytosolic protein and BCDO2 being located in
      the mitochondria. Expression of BCMO1 in tissues other than the intestine has
      recently revealed its function for tissue-specific retinoid metabolism with
      importance in embryogenesis and lipid metabolism. On the other hand, biological
      activity of BCDO2 metabolites has been shown to be important in protecting
      against carotenoid-induced mitochondrial dysfunction. Single-nucleotide
      polymorphisms (SNPs) such as R267S and A379V in BCMO1 can partly explain inter
      individual variations observed in carotenoid metabolism. Advancing knowledge
      about the physiological role of these two enzymes will contribute to
      understanding the importance of carotenoids in health and disease.

PMID- 22147586
TI  - Cellular electrophysiological abnormalities in dyssynchronous hearts and during
      CRT.
AB  - To date, cardiac resynchronization therapy remains the only treatment that
      enhances systolic function while improving long-term outcome and survival.
      Dyssynchronous heart failure is characterized by profound global as well as
      regional cellular and molecular changes, many of which are not observed in
      synchronous heart failure. The beneficial effects of CRT on myofilament function,
      G protein-coupled receptor signaling, and adrenergic response are important
      components for restoring cardiac reserve and reducing arrhythmia, both major
      limitations in heart failure. Here, we review the molecular alterations
      associated with dyssynchronous heart failure and their reversibility induced by
      cardiac resynchronization therapy.

PMID- 22147587
TI  - Cognitive inflexibility as a prospective predictor of suicidal ideation among
      young adults with a suicide attempt history.
AB  - BACKGROUND: Previous studies suggest that people attempt suicide because they are
      cognitively inflexible, but past research suggesting a link between cognitive
      inflexibility and suicidal thoughts and behavior has been limited by cross
      sectional designs. This study examined whether cognitive inflexibility
      differentially and prospectively predicted suicidal ideation among young adults
      with and without a history of a suicide attempt. METHODS: A sample of 45 young
      adults with (n = 13) or without (n = 32) a suicide attempt history completed the
      Wisconsin Card Sorting Test (WCST), a diagnostic interview, and self-report
      measures of hopelessness, depressive symptoms, and suicidal ideation, and were
      followed up 6 months later to reassess suicidal ideation. RESULTS: Cognitive
      inflexibility, as measured by perseverative errors on the WCST, predicted
      suicidal ideation at 6-month follow-up, among suicide attempters, but not among
      nonattempters, adjusting for the presence of a baseline mood or anxiety
      diagnosis, hopelessness, and baseline suicidal ideation. CONCLUSIONS: Cognitive
      inflexibility may increase vulnerability to suicidal ideation over time among
      individuals with a previous suicide attempt history. Implications for
      interventions with suicide attempters are discussed.

PMID- 22147588
TI  - Destructive role of myeloid differentiation factor 88 and protective role of TRIF
      in interleukin-17-dependent arthritis in mice.
AB  - OBJECTIVE: Increasing evidence indicates the involvement of Toll-like receptors
      (TLRs) in the progression of arthritis; however, the contribution of the two
      signaling pathways used by TLRs, which are mediated by myeloid differentiation
      factor 88 (MyD88) and TRIF, remains unclear. The objective of this study was to
      investigate the specific roles of MyD88 and TRIF in chronic experimental
      arthritis and the accompanying adaptive immune responses. METHODS: Chronic
      arthritis was induced in wild-type, MyD88(-/-) , and Trif(lps2)  (TRIF(-/-) )
      mice by repetitive intraarticular injections of streptococcal cell wall (SCW)
      fragments. SCW-specific T cell and B cell responses, joint swelling, and
      histopathologic changes were analyzed during chronic arthritis. RESULTS: Both
      MyD88 and TRIF pathways contributed to antigen-specific T cell proliferation and
      antibody production, with the MyD88 pathway playing the dominant role. The
      severity of joint swelling and synovial inflammation, as well as the
      histopathologic damage to cartilage and bone, was strongly dependent on MyD88
      signaling, whereas TRIF was redundant. MyD88 signaling was critical for the
      development of pathogenic T cell response (i.e., interleukin-17 [IL-17]
      production) in response to SCW antigen. Interestingly, when the T cell-dependent
      phase was prolonged, TRIF signaling appeared to down-regulate bone erosion, an
      effect accompanied by an inhibitory effect on IL-17 production. CONCLUSION: This
      study reveals a central role of MyD88 and a counterregulatory function of TRIF in
      T cell-driven arthritis. The findings provide a rationale for a pathway-specific
      interference in order to block the pathogenic features and to preserve or
      stimulate the beneficial aspects of TLR signaling.

PMID- 22147590
TI  - Predator-recognition training: a conservation strategy to increase postrelease
      survival of hellbenders in head-starting programs.
AB  - For species with declining populations, captive rearing with subsequent release
      into natural habitats ("head-starting") is often used as part of a conservation
      strategy. One challenge to head-starting programs is that head-started
      individuals can suffer high rates of postrelease predation. Head-starting
      programs are currently being established for hellbenders (Cryptobrancus
      alleganeinsis), large aquatic salamanders that are experiencing population
      declines throughout much of the species' range. Although hellbenders have innate
      recognition of many predators, inexperienced juveniles show only weak recognition
      of introduced trout. We used a classical conditioning protocol to train captive
      reared hellbender larvae to show fright responses to the scent of trout. We
      exposed hellbender larvae to trout-scented water plus a hellbender distress
      secretion during training trials. In a subsequent test, these larvae responded to
      trout cues alone with a fright response; control larvae that were trained with
      the trout scent plus a blank control did not show a fright response to the trout
      cues. Learning was specific to trout because trained larvae did not respond to
      water that had been scented by a suckermouth catfish. Although a number of
      details remain to be addressed concerning standardized procedures, we recommend
      that head-starting programs for hellbenders include trout-recognition training.

PMID- 22147589
TI  - Single breathhold noncontrast thoracic MRA using highly accelerated parallel
      imaging with a 32-element coil array.
AB  - PURPOSE: To evaluate the feasibility of performing single breathhold three
      dimensional (3D) thoracic noncontrast MR angiography (NC-MRA) using highly
      accelerated parallel imaging. MATERIALS AND METHODS: We developed a single
      breathhold NC MRA pulse sequence using balanced steady state free precession
      (SSFP) readout and highly accelerated parallel imaging. In 17 subjects, highly
      accelerated noncontrast MRA was compared against electrocardiogram-triggered
      contrast-enhanced MRA. Anonymized images were randomized for blinded review by
      two independent readers for image quality, artifact severity in eight defined
      vessel segments and aortic dimensions in six standard sites. NC-MRA and CE-MRA
      were compared in terms of these measures using paired sample t- and Wilcoxon
      tests. RESULTS: The overall image quality (3.21 +/- 0.68 for NC-MRA versus 3.12
      +/- 0.71 for CE-MRA) and artifact (2.87 +/- 1.01 for NC-MRA versus 2.92 +/- 0.87
      for CE-MRA) scores were not significantly different, but there were significant
      differences for the great vessel and coronary artery origins. NC-MRA demonstrated
      significantly lower aortic diameter measurements compared with CE-MRA; however,
      this difference was not considered clinically relevant (>3 mm difference) for
      less than 12% of segments, most commonly at the sinotubular junction. Mean total
      scan time was significantly lower for NC-MRA compared with CE-MRA (18.2 +/- 6.0 s
      versus 28.1 +/- 5.4 s, respectively; P < 0.05). CONCLUSION: Single breathhold NC
      MRA is feasible and can be a useful alternative for evaluation and follow-up of
      thoracic aortic diseases.

PMID- 22147591
TI  - Species identification and chromosome variation of captive two-toed sloths.
AB  - Two-toed sloth species, Linnaeus's and Hoffmman's, are frequent residents of zoo
      collections in North America. However, species identification has always been
      problematic because of their large overlap in external morphology, which
      represents an obstacle to the captive breeding program. We describe here a PCR
      based technique that allows species identification of two-toed sloths without
      requiring sequencing, by using a mitochondrial marker (COI gene) and restriction
      enzyme assay. We also report intra- and inter-specific patterns of chromosome
      variation in captive two-toed sloths. Molecularly, we identified 22 samples of
      Linnaeus's and Hoffmman's two-toed sloths corresponding to 14 and 8 individuals,
      respectively. One animal was identified as a hybrid using the nuclear gene Enam
      having alleles derived from both species. The chromosome number in Hoffman's two
      toed sloths showed low variation ranging only between 50 and 51. In contrast,
      Linnaeus's two-toed sloths appeared to vary widely, with diploid numbers ranging
      from 53 to 67, suggesting distinct geographic groups. The species identification
      method presented here represents a low-cost easy-to-use tool that will help to
      improve management of the captive population of two-toed sloths.

PMID- 22147592
TI  - Genetic evaluation of the Association of Zoos and Aquariums Matschie's tree
      kangaroo (Dendrolagus matschiei) captive breeding program.
AB  - Matschie's tree kangaroo (Dendrolagus matschiei) is an endangered species that
      has been bred in captivity since the 1970s. In 1992, the Tree Kangaroo Species
      Survival Plan((r)) (TKSSP) was established to coordinate the captive management
      of Association of Zoos and Aquariums (AZA) D. matschiei. The TKSSP makes annual
      breeding recommendations primarily based on the mean kinship (MK) strategy.
      Captive breeding programs often use the MK strategy to preserve genetic diversity
      in small populations-to avoid the negative consequences of inbreeding and retain
      their adaptive potential. The ability of a captive breeding program to retain the
      population's genetic diversity over time can be evaluated by comparing the
      genetic diversity of the captive population to wild populations. We analyzed DNA
      extracted from blood and fecal samples from AZA (n = 71), captive (n = 28), and
      wild (n = 22) D. matschiei using eight microsatellite markers and sequenced the
      partial mitochondrial DNA control region gene. AZA D. matschiei had a similar
      expected heterozygosity (H(e) = 0.595 +/- 0.184) compared with wild D. matschiei
      (H(e) = 0.628 +/- 0.143), but they had different allelic frequencies (F(ST) =
      0.126; P < 0.001). AZA D. matschiei haplotype diversity was almost two times
      lower than wild D. matschiei H = 0.740 +/- 0.063. These data will assist
      management of AZA D. matschiei and serve as a baseline for AZA and wild D.
      matschiei genetic diversity values that could be used to monitor future changes
      in their genetic diversity.

PMID- 22147593
TI  - Note on optimizing environmental enrichment: a study of fennec fox and zoo
      guests.
AB  - Environmental enrichment is widely used to stimulate animal time budgets that
      seem more natural and diverse than those of unenriched animals. Uncertainty of
      reward is a suggested means to maintain enrichment's efficacy. Foraging tasks are
      widely applied in zoo animal enrichment, yet few rely on the logic of optimal
      foraging theory to help maintain animal motivation. We applied a foraging
      strategy to zoo housed fennec foxes as enrichment. We varied only the probability
      of when and where food would occur in the animals' exhibit. Our methods increased
      behavioral diversity, animal activity, and stimulated guest interest in the
      exhibit.

PMID- 22147594
TI  - Role of Brazilian zoos in ex situ bird conservation: from 1981 to 2005.
AB  - Zoos may play an important role in conservation when they maintain and breed
      large numbers of animals that are threatened with extinction. Bird conservation
      is in a privileged situation owing to the extensive biological information
      available about this class. Annual inventories produced by the "Sociedade de
      Zoologicos do Brasil" in the years 1981, 1990, 2000, and 2005 were analyzed.
      Variables, such as the number of zoos per geographic region; number of birds
      held; number of bird species in each IUCN threat category; number of exotic and
      native bird species; number of potentially breeding bird species; number of bird
      species in each order; and number of threatened bird species breeding, were
      analyzed. Brazilian zoos kept more than 350 bird species. The number of bird
      species and specimens held by the Brazilian Zoos increased from 1981 to 2000, but
      decreased in 2005. The same pattern was observed for the number of species in
      each IUCN threat category. Results showed that the potential of the Brazilian
      zoos in bird conservation needs to be enhanced because they maintain threatened
      species but do not implement systematic genetic, reproductive, or behavioral
      management protocols for most species.

PMID- 22147595
TI  - Effect of an increase in environmental temperature on testicular androgenesis and
      spermatogenesis in toad (Bufo melanostictus) during hibernating season.
AB  - Activities of key testicular androgenic enzymes [Delta(5), 3beta-hydroxysteroid
      dehydrogenase (Delta(5), 3beta-HSD) and 17beta-hydroxysteroid dehydrogenase
      (17beta-HSD)], plasma levels of testosterone, and testicular gametogenic
      activities were studied in heat-exposed adult male toads during hibernating
      season for two consecutive years. Exposure of toads to an elevated environmental
      temperature for 14 and 21 days resulted in significant elevation of testicular
      Delta(5), 3beta-HSD and 17beta-HSD activities, along with plasma levels of
      testosterone. Testicular gametogenic activity, by means of quantity of all stages
      of spermatogenic cycle, were elevated significantly at the same experimental
      schedule, but 7 days of heat exposure resulted in significant elevation only in
      stage IV. The results indicated that environmental temperature is an important
      modulator of breeding activities of male toads. It also demonstrated that
      testicular activities in seasonally breeding toads are probably not linked to
      hibernating cycle.

PMID- 22147596
TI  - Observation of reproductive cycle of female yellow-margined box turtle (Cuora
      flavomarginata) using radiography and ultrasonography.
AB  - This study presents a combination of radiography and ultrasonography to observe
      the reproductive cycle of 24 captive female yellow-margined box turtles in
      Taiwan. Radiography was mainly used to monitor clutch size, whereas
      ultrasonography was applied to detect changes in the follicles throughout the
      year. The observation of the 24 female turtles was performed from April 2007 to
      June 2008. Their average carapace length was 16.62 +/- 1.66 cm and their average
      body weight was 812 +/- 164.98 g. The mean clutch size was three (87 eggs/29
      clutches) and the reproductive frequency was 95.83% (23/24). Double clutches were
      detected in 79.2%, and 20.8% had single clutches. Ovulation occurred from March
      through August, and the average follicular diameter was 2.16 +/- 0.18 cm.
      Follicles entered the latent period in October (at 1.54 +/- 0.26 cm), and
      vitellogenesis of the next reproductive cycle began in November. Using
      radiography, the eggshell could be detected on the ninth day after ovulation. The
      average period of the single clutch group was 6.9 weeks (range 5.1-8.5 weeks). In
      the double clutch group, the average period of the first clutch was 5.5 weeks
      (range 4-7.8 weeks) and that of the second clutch was 5.2 weeks (range 4-7.8
      weeks). This study has advanced the understanding of reproductive physiology of
      yellow-margined box turtle and established a valuable and practical model for
      comparative study of the reproductive physiology of other chelonians.

PMID- 22147597
TI  - Youth civic development: historical context and emerging issues.
AB  - The civic domain has taken its place in the scholarship and practice of youth
      development. From the beginning, the field has focused on youth as assets who
      contribute to the common good of their communities. Work at the cutting edge of
      this field integrates research and practice and focuses on the civic
      incorporation of groups who often have been marginalized from mainstream society.
      The body of work also extends topics of relevance to human development by
      considering themes of justice, social responsibility, critical consciousness, and
      collective action.

PMID- 22147598
TI  - The developmental roots of social responsibility in childhood and adolescence.
AB  - Social responsibility is a value orientation, rooted in democratic relationships
      with others and moral principles of care and justice, that motivates certain
      civic actions. Given its relevance for building stronger relationships and
      communities, the development of social responsibility within individuals should
      be a more concerted focus for developmental scholars and youth practitioners.
      During childhood and adolescence, the developmental roots of individuals' social
      responsibility lie in the growth of executive function, empathy and emotion
      regulation, and identity. Efforts to cultivate children and adolescents' social
      responsibility in the proximal settings of their everyday lives should emphasize
      modeling prosocial behaviors, communicating concerns for others, and creating
      opportunities to practice civic skills.

PMID- 22147599
TI  - Taking stock of youth organizing: an interdisciplinary perspective.
AB  - Youth organizing combines elements of community organizing, with its emphasis on
      ordinary people working collectively to advance shared interests, and positive
      youth development, with its emphasis on asset-based approaches to working with
      young people. It is expanding from an innovative, but marginal approach to youth
      and community development into a more widely recognized model for practice among
      nonprofit organizations and foundations. Along the way, it has garnered attention
      from researchers interested in civic engagement, social movements, and
      resiliency. A growing body of published work evidences the increasing interest of
      researchers, who have applied an assortment of theoretical perspectives to their
      observations of youth organizing processes. Through an appraisal of the current
      state of this still-emerging area of practice and research, including case
      examples, the authors identify common elements of the practice of youth
      organizing--relationship development, popular education, social action, and
      participatory research and evaluation--and conclude with a discussion of
      promising future directions for research and practice.

PMID- 22147600
TI  - Critical consciousness: current status and future directions.
AB  - In this chapter, the authors consider Paulo Freire's construct of critical
      consciousness (CC) and why it deserves more attention in research and discourse
      on youth political and civic development. His approach to education and similar
      ideas by other scholars of liberation aims to foster a critical analysis of
      society--and one's status within it--using egalitarian, empowering, and
      interactive methods. The aim is social change as well as learning, which makes
      these ideas especially relevant to the structural injustice faced by marginalized
      youth. From their review of these ideas, the authors derive three core CC
      components: critical reflection, political efficacy, and critical action. They
      highlight promising research related to these constructs and innovative applied
      work including youth action-research methodology. Their conclusion offers ideas
      for closing some of the critical gaps in CC theory and research.

PMID- 22147601
TI  - "Unapologetic and unafraid": immigrant youth come out from the shadows.
AB  - Young immigrants are challenging the boundaries of citizenship and insisting on
      their human rights. This chapter examines the civic lives of immigrant youth
      through the case of Latina/os, exploring the paradox of their apparent low civic
      education and engagement levels and remarkable participation in recent protests.
      After an overview of demographics and what we know about immigrant youth civic
      life, the focus shifts to the undocumented. Many retain a sense of community
      obligation, yet because of their developmental stage and U.S. education, their
      engagement differs from that of their parents' generation. Young immigrants are
      reconfiguring organizing and reenergizing U.S. democracy through their use of new
      information technologies.

PMID- 22147602
TI  - Early educational foundations for the development of civic responsibility: an
      African experience.
AB  - An innovative curriculum designed to foster the development of social
      responsibility among pre-adolescent children was introduced at a rural Zambian
      primary school. The curriculum invoked Child-to-Child principles focusing on
      health education, advancing a synthesis of Western psychological theories and
      African cultural traditions. The teacher sought to democratize the educational
      process through cooperative learning in mixed-gender, mixed-social-class, and
      mixed-ability study groups. Learners engaged in community service activities and
      contributed to the nurturant care of younger children. Young adults interviewed
      seventeen years after completing the program recalled their experience and
      reflected on how it had promoted their personal agency, cooperative disposition,
      and civic responsibility in early adulthood.

PMID- 22147603
TI  - Youth civic development: theorizing a domain with evidence from different
      cultural contexts.
AB  - The authors use examples of youth civic engagement from Chile, South Africa,
      Central/Eastern Europe, and the United States--and also emphasize diversities
      among youth from different subgroups within countries--to illustrate common
      elements of the civic domain of youth development. These include the primacy of
      collective activity for forming political identities and ideas and the greater
      heterogeneity of civic compared to other discretionary activities, the groupways
      or accumulated opportunities for acting due to the groups (social class, gender,
      ethnic, caste, etc.) to which a young person belongs, and the role of mediating
      institutions (schools, community-based organizations, etc.) as spaces where
      youths' actions contribute to political stability and change.

PMID- 22147604
TI  - Laryngeal electromyography for prognosis of vocal fold palsy: a meta-analysis.
AB  - OBJECTIVES/HYPOTHESIS: To analyze existing evidence regarding utility of
      laryngeal electromyography (LEMG) for prognosis in cases of vocal fold palsy
      (VFP). STUDY DESIGN: Meta-analysis of studies reporting LEMG results and clinical
      outcomes in 503 patients with of VFP identified by literature search. METHODS:
      Studies were identified by literature search. Method of diagnosis, interval to
      LEMG, criteria for prognostication, and outcome were assessed. Criteria for
      prognosis were standardized to the extent possible across all studies, and
      studies were checked for consistency in outcome measures and assessments. Pooled
      data were subjected to statistical analysis. RESULTS: A total of 296/503 patients
      (58.8%) had findings predictive with poor prognosis, whereas 207/503 (41.2%) had
      findings of recovery. According to laryngoscopic examination, 269/296 patients
      with predicted poor recovery had poor recovery (positive predictive value=90.9%),
      whereas 27/296 (9.1%) had good recovery. In patients with findings consistent
      with recovery, 115/207 (negative predictive value=55.6%) noted return of motion,
      whereas 88/207 (44.4%) did not. The odds ratio was 11.56 with 95% confidence
      interval of 7.10-18.81. CONCLUSIONS: LEMG is a good predictor of poor recovery in
      patients with VFP and is clinically useful in identifying candidates for early
      definitive intervention.

PMID- 22147606
TI  - Host-derived pericytes and Sca-1+ cells predominate in the MART-1- stroma
      fraction of experimentally induced melanoma.
AB  - Identification of cell types in tumor-associated stroma that are involved in the
      development of melanoma is hampered by their heterogeneity. The authors used flow
      cytometry and immunohistochemistry to demonstrate that anti-MART-1 antibodies can
      discriminate between melanoma and stroma cells. They investigated the cellular
      composition of the MART-1-, non-hematopoietic melanoma-associated stroma, finding
      it consisted mainly of Sca-1+ and CD146+ cells. These cell types were also
      observed in the skin and muscle adjacent to developing melanomas. The Sca-1+ cell
      population was observed distributed in the epidermis, hair follicle bulges, and
      tumor capsule. The CD146+ population was found distributed within the tumor,
      mainly associated with blood vessels in a perivascular location. In addition to a
      perivascular distribution, CD146+ cells expressed alpha-smooth muscle actin,
      lacked expression of endothelial markers CD31 and CD34, and were therefore
      identified as pericytes. Pericytes were found to be associated with CD31+
      endothelial cells; however, some pericytes were also observed associated with
      CD31-, MART-1+ B16 melanoma cells that appeared to form blood vessel structures.
      Furthermore, the authors observed extensive nuclear expression of HIF-1alpha in
      melanoma and stroma cells, suggesting hypoxia is an important factor associated
      with the melanoma microenvironment and vascularization. The results suggest that
      pericytes and Sca-1+ stroma cells are important contributors to melanoma
      development.

PMID- 22147605
TI  - The skeletal muscle satellite cell: still young and fascinating at 50.
AB  - The skeletal muscle satellite cell was first described and named based on its
      anatomic location between the myofiber plasma and basement membranes. In 1961,
      two independent studies by Alexander Mauro and Bernard Katz provided the first
      electron microscopic descriptions of satellite cells in frog and rat muscles.
      These cells were soon detected in other vertebrates and acquired candidacy as the
      source of myogenic cells needed for myofiber growth and repair throughout life.
      Cultures of isolated myofibers and, subsequently, transplantation of single
      myofibers demonstrated that satellite cells were myogenic progenitors. More
      recently, satellite cells were redefined as myogenic stem cells given their
      ability to self-renew in addition to producing differentiated progeny.
      Identification of distinctively expressed molecular markers, in particular Pax7,
      has facilitated detection of satellite cells using light microscopy.
      Notwithstanding the remarkable progress made since the discovery of satellite
      cells, researchers have looked for alternative cells with myogenic capacity that
      can potentially be used for whole body cell-based therapy of skeletal muscle.
      Yet, new studies show that inducible ablation of satellite cells in adult muscle
      impairs myofiber regeneration. Thus, on the 50th anniversary since its discovery,
      the satellite cell's indispensable role in muscle repair has been reaffirmed.

PMID- 22147608
TI  - Effects of long-term storage on the detection of proteins, DNA, and mRNA in
      tissue microarray slides.
AB  - Storage of tissue slides has been claimed to induce dramatically reduced antigen
      detection particularly for immunohistochemistry (IHC). With tissue microarrays,
      the necessity to serially cut blocks in order to obtain as much material as
      possible is obvious. The presumed adverse effect of storage might hamper such an
      approach. The authors designed an experimental setting consisting of four
      different storage conditions with storage time of tissue slides of up to 1 year.
      Detection of proteins, DNA, and mRNA was performed using IHC and in situ
      hybridization techniques. Slight but significant changes in IHC occurred over
      time. The most important factor is the primary antibody used: four showed no
      significant changes, whereas limited decreases in 8 antibodies could be detected
      by image analysis. Whether the antigen was nuclear or cytoplasmic/membranous did
      not matter. No major differences between different storage conditions could be
      shown, but storage at 4C was overall the best procedure. Furthermore, gene copy
      number aberrations, chromosomal translocations, and the presence of mRNA could be
      detected on slides stored up to 1 year. In conclusion, in tissues optimally
      formalin fixed and using modern histological techniques, only minute changes in
      tissue antigenicity are induced by long-term storage.

PMID- 22147609
TI  - [Cardiac insufficiency: acute right heart failure].
AB  - Acute right heart failure (RHF) is a frequent and severe complication during
      perioperative and intensive care treatment in intensive care units (ICUs). The
      most common causes are pulmonary hypertension, left heart failure, pulmonary
      embolism, sepsis, acute lung injury (ALI) and thoracosurgical procedures. Acute
      RHF is not only a major contributor to morbidity and mortality; it also
      influences efficacy and outcome of routinely performed procedures, such as
      vasopressors, in critically ill patients. In contrast to the left ventricle, the
      right ventricle's physiology and pathophysiology are understudied, and the
      diagnosis of acute RHF is frequently challenging. Although many drugs are
      available for the treatment of RHF, randomized trials for this setting are still
      missing. This article gives an overview of aetiology and pathogenesis of RHF and
      reviews the diagnostic and therapeutic interventions currently available for
      providers in anaesthesiology and critical care.

PMID- 22147607
TI  - TNIP1, a retinoic acid receptor corepressor and A20-binding inhibitor of NF
      kappaB, distributes to both nuclear and cytoplasmic locations.
AB  - An increasingly wide range of functions, from repression of NF-kappaB signaling
      to protection from apoptosis, is being recognized for tumor necrosis factor alpha
      induced protein 3-interacting protein 1 (TNIP1). The authors recently
      demonstrated TNIP1 interaction with and repression of liganded retinoic acid
      receptors, distinguishing it from the more typical NCoR and SMRT corepressors,
      which function only in the absence of ligand. To improve their understanding of
      TNIP1's roles in physiologic and pathologic events, the authors examined its
      distribution in normal and malignant human tissues and cultured cells. They found
      cytoplasmic and nuclear TNIP1 in normal skin keratinocytes as it colocalized with
      retinoic acid receptor alpha, one of the nuclear receptors it corepresses.
      Nuclear and cytoplasmic TNIP1 was also found in the malignant keratinocytes of
      squamous cell carcinomas. Compared to adjacent normal tissues of other organs,
      TNIP1 staining and distribution varied with increased levels in esophageal cancer
      and marked decreases in prostate cancer. The varying levels and distribution of
      TNIP1 in normal and disease state tissues could be expected to affect processes
      in which TNIP1 is involved, such as NF-kappaB and nuclear receptor signaling,
      possibly contributing to the disease course or response to therapies targeting
      these key players of cell growth and differentiation.

PMID- 22147610
TI  - [Acute respiratory insufficiency: prehospital management of obstructive pulmonary
      diseases].
AB  - Acute respiratory insufficiency due to obstructive pulmonary diseases is a common
      problem presenting to the emergency medical service. Most frequent causes are
      acute asthma attacks or acute exacerbations of chronic obstructive pulmonary
      disease (COPD). The preclinical differentiation of both diseases may be
      difficult, so that the diagnosis is often made by precise anamnesis. This article
      reviews the prehospital management of asthma and COPD, including pharmacological
      options and techniques of mechanical ventilatory support (non-invasive vs.
      invasive).

PMID- 22147611
TI  - [Pain therapy in pediatric oncology: pain experience, drugs and
      pharmacokinetics].
AB  - Paediatric cancer patients often experience fear and pain from the disease but
      also in connection with the necessary diagnostic and therapeutic procedures. The
      treatment of pain is a priority for all patients, especially for critically ill
      children because of their vulnerability and limited understanding. The experience
      of pain is always subjective and depends on the age, the pain experience and the
      environment.In contrast to adults, it is often difficult to detect character of
      pain, pain intensity and pain localization in very young patients. Diagnostic and
      therapeutic procedures are performed in analgosedation for a given drug scheme by
      a pediatrician experienced in intensive care.In addition, a local anesthetic for
      an access system/lumbar punctures in the form of EMLA(r) patch is to be carried
      out. A rapid and effective treatment of pain and appropriate analgesia can
      prevent patients from being traumatized.For severe pain, malignancy- or
      chemotherapy-induced (eg. mucositis WHO grade 3 and 4) initial use of strong
      opiates is recommended instead of climbing the WHO ladder. For strong opiates,
      there is no maximum dose, as long as a dose increase leads to clinically
      observable increase in analgesia, without severe side effects. Patient-controlled
      analgesia with morphine as continuous subcutaneous or intravenous infusions and
      the possibility of a bolus injection is suited for children aged 6 years. A
      measurement of O2-saturation is essential during this infusion. Prophylactic
      approaches also must be used consistently in regard to the acute side effect of
      opiate treatment. Good experience, we have also made a non-drug therapy, e.g.
      personnel/physical affection, cuddling, massage, etc.The choice of analgesia
      depends on the nature and cause of pain. In neuropathic pain or phantom pain
      coanalgetics should be used to effectively treat pain in young patients.
      Different analgesic treatment approaches of the appropriate indications and
      adverse effects are presented. A particular challenge for the pediatrician is the
      sufficient and adequate pain therapy in palliative care.

PMID- 22147612
TI  - [DGAI-certified course series anaesthesia focused sonography: module 1: basics of
      sonography].
AB  - Understanding the principles of wave physics paves the way for appropriate
      utilization and interpretation of sonography. In module 1 of the course series
      "Anesthesia Focused Sonography", the course participants will learn by lectures
      and practical training, how ultrasonic waves emerge, how they travel in human
      tissue, and how a picture is generated from their echo signals. Furthermore, the
      technology of an ultrasound system and the development of artifacts will be
      demonstrated; moreover, the Doppler effect and its implementation into current
      sonographic procedures will be presented as a central theme.

PMID- 22147613
TI  - [The DGAI training module 3 in anaesthetic focussed sonography: neurosonography].
AB  - Identification of the right puncture site and the target structures are mandatory
      in performing nerve blocks. Ultrasound is a new method, that visualizes target
      structures as well as the injection and spread of local anaesthetic solution. The
      presented module 3 neurosonography is part of the didactic concept
      "anaesthesiology focussed sonography" developed by the german society of
      anaesthesiology and intensive care. It contains all essential nerve blocks of the
      upper and lower limb. Additionally the structural requirements to provide the
      course are included.

PMID- 22147614
TI  - Permeability of ergot alkaloids across the blood-brain barrier in vitro and
      influence on the barrier integrity.
AB  - SCOPE: Ergot alkaloids are secondary metabolites of Claviceps spp. and they have
      been in the focus of research for many years. Experiments focusing on ergotamine
      as a former migraine drug referring to the ability to reach the brain revealed
      controversial results. The question to which extent ergot alkaloids are able to
      cross the blood-brain barrier is still not answered. METHODS AND RESULTS: In
      order to answer this question we have studied the ability of ergot alkaloids to
      penetrate the blood-brain barrier in a well established in vitro model system
      using primary porcine brain endothelial cells. It could clearly be demonstrated
      that ergot alkaloids are able to cross the blood-brain barrier in high quantities
      in only a few hours. We could further identify an active transport for
      ergometrine as a substrate for the BCRP/ABCG2 transporter. Investigations
      concerning barrier integrity properties have identified ergocristinine as a
      potent substance to accumulate in these cells ultimately leading to a weakened
      barrier function. CONCLUSION: For the first time we could show that the so far as
      biologically inactive described 8-(S) isomers of ergot alkaloids seem to have an
      influence on barrier integrity underlining the necessity for a risk assessment of
      ergot alkaloids in food and feed.

PMID- 22147615
TI  - Synthesis and conformational analysis of efrapeptins.
AB  - The efrapeptin family of peptide antibiotics produced by the fungus Tolypocladium
      niveum, and the neo-efrapeptins from the fungus Geotrichum candidumare inhibitors
      of F(1)-ATPase with promising antitumor, antimalaria, and insecticidal activity.
      They are rich in C(alpha)-dialkyl amino acids (Aib, Iva, Acc) and contain one
      beta-alanine and several pipecolic acid residues. The C-terminus bears an unusual
      heterocyclic cationic cap. The efrapeptins C-G and three analogues of efrapeptin
      C were synthesized using alpha-azido carboxylic acids as masked amino acid
      derivatives. All compounds display inhibitory activity toward F(1)-ATPase. The
      conformation in solution of the peptides was investigated with electronic CD
      spectroscopy, FT-IR spectroscopy, and VCD spectroscopy. All efrapeptins and most
      efrapeptin analogues were shown to adopt helical conformations in solution. In
      the case of efrapeptin C, VCD spectra proved that a 3(10)-helix prevails. In
      addition, efrapeptin C was conformationally studied in detail with NMR and
      molecular modeling. Besides NOE distance restraints, residual dipolar couplings
      (RDC) observed upon partial alignment with stretched PDMS gels were used for the
      conformational analysis and confirmed the 3(10)-helical conformation.

PMID- 22147616
TI  - Quantitative I-123 mIBG SPECT in differentiating abnormal and normal mIBG
      myocardial uptake.
AB  - BACKGROUND: The purpose of this study was to evaluate global quantitation of
      cardiac uptake on I-123 mIBG SPECT. METHODS: The study included a pilot group of
      67 subjects and a validation group of 1,051 subjects. SPECT images were
      reconstructed by filtered backprojection, ordered subsets expectation
      maximization, and deconvolution of septal penetration, respectively. SPECT heart
      to-mediastinum ratio (H/M) was calculated by comparing the mean counts between
      heart and mediastinum volumes of interest drawn on transaxial images. Receiver
      operating characteristic (ROC) analysis was used to assess the capability of each
      SPECT method to differentiate the heart disease subjects from controls in
      comparison with that of the planar H/M. RESULTS: In the validation group, the
      areas under the ROC curves were not significantly different between the SPECT and
      planar H/M. Order subsets expectation maximization had significantly larger area
      under the ROC curve than the other two SPECT methods. CONCLUSION: H/M obtained
      from I-123 mIBG SPECT was equivalent to the planar H/M for differentiating
      between subjects with normal and abnormal mIBG uptake. Global quantification of
      cardiac I-123 mIBG SPECT may represent a viable alternative to the planar H/M.

PMID- 22147617
TI  - Reduced stress dose with rapid acquisition CZT SPECT MPI in a non-obese clinical
      population: comparison to coronary angiography.
AB  - BACKGROUND: Cadmium Zinc Telluride (CZT) SPECT camera technology has the
      potential to reduce patient's radiation exposure and shorten imaging time. This
      study evaluated the correlation of low stress tracer dose, rapid CZT SPECT
      myocardial perfusion imaging (MPI) to coronary angiography in a <200-lbs
      population to further validate its ability to achieve both goals while preserving
      diagnostic accuracy. METHODS: All patients who had a low-dose stress (<=15 mCi)
      Tc-99m sestamibi SPECT MPI study using a CZT camera (GE Discovery NM 530c) with 3
      to 5-minute image acquisition over a 2-year period followed by a coronary
      angiogram within 2 months were included. Patients with a history of coronary
      revascularization, left ventricular dysfunction, and LBBB or paced rhythms were
      excluded. Both MPI studies and coronary angiograms were interpreted by blinded
      readers and coronary artery disease (CAD) was defined as >=70% stenosis. RESULTS:
      A total of 71 patients were included with a mean age of 64 years, 55% male, and a
      BMI of 25.4 kg/m(2) with an average stress dose of 13.3 mCi. Exercise stress was
      performed in 54% of patients and vasodilator pharmacologic stress in 46%.
      Sensitivity was 89%, specificity was 66%, and accuracy was 78% for detecting
      obstructive CAD. CONCLUSIONS: In this group of non-obese patients undergoing low
      stress dose imaging, high-efficiency CZT SPECT imaging demonstrated a high
      sensitivity, specificity, and accuracy for detecting obstructive epicardial CAD
      with a greatly reduced imaging time.

PMID- 22147618
TI  - Assessing risk in acute chest pain: The value of stress myocardial perfusion
      imaging in patients admitted through the emergency department.
AB  - BACKGROUND: To prospectively assess the clinical value of stress-gated myocardial
      single photon emission computed tomography (SPECT) for triaging patients admitted
      through the emergency department (ED) with acute chest pain (ACP). METHODS:
      Prospective, observational cohort study in 1,576 consecutive patients who were
      evaluated for ACP over a 29-month period. Stress SPECT was performed within 24
      hours of admission from the ED. Analysis included quantification of total and
      ischemic left ventricular perfusion defect size (PDS). Cardiac events were
      defined as an acute coronary syndrome during the index hospitalization or in
      follow-up over 7.3 +/- 2.8 months. RESULTS: Eighty-five cardiac events occurred
      in 77 patients (4.9%). SPECT was abnormal in 135 patients (8.6%) of whom 83
      (61.5%) had a reversible defect. Event rates were significantly higher in
      patients with an abnormal (40%) versus a normal (1.6%) SPECT (P < .0001); and in
      those with a (1) large (>15%) versus small (<=15%) PDS (50.0% vs 33.7%, P = .05)
      and (2) large (>10%) versus small (<=10%) ischemic PDS (87.5% vs 42.4%, P <
      .0001, respectively). SPECT best predicted cardiac events by multivariate
      analysis. The addition of SPECT to clinical variables significantly improved
      overall risk prediction (global chi(2) 103.6 vs 207.1, P < .001). CONCLUSIONS:
      Stress SPECT can accurately assess risk in a heterogeneous group of patients with
      ACP of unclear cardiac etiology, and beyond that provided by a clinical risk
      assessment alone. Our results support the use of stress SPECT for identifying
      very low-risk ACP patients with normal study results who can be safely discharged
      home.

PMID- 22147619
TI  - Advances in cardiac imaging: taking a closer look at PET perfusion imaging :
      American Society of Nuclear Cardiology, Philadelphia, PA, 24 September 2010.

PMID- 22147620
TI  - Engineering Saccharomyces cerevisiae for efficient anaerobic xylose fermentation:
      reflections and perspectives.
AB  - Conversion of the abundant lignocellulosic biomass into ethanol is an
      environmentally sustainable solution to the energy crisis. Fermentation of
      lignocellulosic hydrolysates by Saccharomyces cerevisiae is not cost-effective
      yet as substantial amounts of xylose in the hydrolysates cannot be utilized by
      native S. cerevisiae strains. Extensive studies including both metabolic and
      evolutionary engineering have been carried out to develop an efficient xylose
      fermenting S. cerevisiae strain, yet the ethanol yield and productivity from
      xylose fermentation of the best one are still far below expectation. This review
      compares the engineering approaches and resulted anaerobic xylose fermentation
      performance of recently reported xylose-utilizing S. cerevisiae strains, with the
      aim to understand the intrinsic reason for their low xylose fermentation
      capabilities. These comparative analyses revealed that some of the current
      engineering targets and the so-called "hot issues" might be overrated. Our
      opinions on the underrated parts and future efforts in this field are also
      presented. Overall, this review serves as a comprehensive reference to
      understanding xylose fermentation by S. cerevisiae.

PMID- 22147622
TI  - The powers and pitfalls of payment for performance.

PMID- 22147623
TI  - 'Health Economics' and the evolution of economic evaluation of health
      technologies.

PMID- 22147624
TI  - Let the data be our guide: trends and tools for research on health care
      utilization.

PMID- 22147625
TI  - The developmental origins of health.

PMID- 22147626
TI  - A little learning: reflections on 10 years of NICE technology appraisals.

PMID- 22147627
TI  - Competition, incentives and the English NHS.

PMID- 22147628
TI  - Divide et impera: protecting the growth of health care incomes (COSTS).

PMID- 22147629
TI  - How can we increase resources for health care in the developing world?: is
      (subsidized) voluntary health insurance the answer?

PMID- 22147631
TI  - What are the clinical implications of new onset or worsening anxiety during the
      first two weeks of SSRI treatment for depression?
AB  - OBJECTIVE: To evaluate the prevalence of new onset or worsening of anxiety
      symptoms, as well as their clinical implications, during the first 2 weeks of
      Selective Serotonin Reuptake Inhibitor (SSRI) pharmacotherapy for depression.
      METHOD: Adult outpatients with nonpsychotic major depressive disorder were
      enrolled in an 8-week acute phase SSRI treatment trial at 15 clinical sites
      across the United States. Worsening anxiety was defined as a greater than 2-point
      increase on the Beck Anxiety Inventory (BAI) between baseline and Week 2. New
      onset of anxiety symptoms was ascribed when the BAI baseline rating was 0 and the
      Week 2 value was greater or equal to 2 points on the BAI. RESULTS: Overall, after
      2 weeks of treatment, 48.8% (98 of 201 participants) reported improvement in
      anxiety symptoms, 36.3% (73 of 201) reported minimal symptom change, and 14.9%
      (30 of 201) reported worsening of anxiety symptoms. No association was found
      between change in anxiety symptoms within the first 2 weeks and change in
      depressive symptoms or remission at the end of 8 weeks of treatment. For
      participants with clinically meaningful anxiety symptoms at baseline, however,
      worsening of anxiety during the first 2 weeks of treatment was associated with
      worsening depressive symptoms by 8 weeks (P = .054). CONCLUSIONS: The trajectory
      of anxiety symptom change early in SSRI treatment is an important indicator of
      eventual outcome for outpatients with major depression and baseline anxiety
      symptoms.

PMID- 22147633
TI  - Thyroid disease and compressive symptoms.
AB  - OBJECTIVES/HYPOTHESIS: Compressive symptoms are common in thyroid disease, but
      few studies have focused on the presence, associated factors, and etiology of
      compressive symptoms. STUDY DESIGN: Retrospective review. METHODS: Patients who
      underwent thyroidectomy from 2005 through 2009 were reviewed. The data included
      demographics, indication for surgery, compressive symptoms, complications,
      diagnosis, volume of thyroid gland, presence of inflammation, and follow-up.
      RESULTS: Three hundred thirty-three patients were identified. The mean age was 51
      years, and 82% were female. Fifty-two percent (n=172) of patients experienced
      compressive symptoms preoperatively, including dysphagia (n=131) and shortness of
      breath (n=83). Twenty-six percent (n=86) of patients presented with voice
      changes, and 8% (n=27) complained of odynophagia. Postoperatively, 25 patients
      (8%) continued to have compressive symptoms (P<.0001), and 10 patients (3%)
      developed new compressive symptoms. Compressive symptoms were present in 72%
      (n=21) of patients with lymphocytic thyroiditis, 71% (n=5) of patients with
      anaplastic thyroid cancer, and 60% (n=92) of patients with goiter. The average
      volume of the gland in patients with compressive symptoms was 75.5 mL compared to
      37.1 mL in asymptomatic patients (P<.0001). There was not a significant
      relationship between compressive symptoms and the presence of inflammation
      (P=.869). CONCLUSIONS: Patients with thyroid disease frequently present with
      compressive symptoms, and the majority of patients experience relief
      postoperatively. The volume of the thyroid gland is associated with compressive
      symptoms along with additional contributing factors.

PMID- 22147632
TI  - The JAK inhibitor tofacitinib regulates synovitis through inhibition of
      interferon-gamma and interleukin-17 production by human CD4+ T cells.
AB  - OBJECTIVE: Tofacitinib (CP-690,550) is a novel JAK inhibitor that is currently in
      clinical trials for the treatment of rheumatoid arthritis (RA). The aim of this
      study was to examine the effects of tofacitinib in vitro and in vivo in RA, in
      order to elucidate the role of JAK in the disease process. METHODS: CD4+ T cells,
      CD14+ monocytes, and synovial fibroblasts (SFs) were purified from the synovium
      and peripheral blood of patients with RA and were evaluated for the effect of
      tofacitinib on cytokine production and cell proliferation. For in vivo analysis,
      synovium and cartilage samples obtained from patients with RA were implanted in
      immunodeficient mice (SCID-HuRAg mice), and tofacitinib was administered via an
      osmotic minipump. RESULTS: Tofacitinib treatment of CD4+ T cells originating from
      synovium and peripheral blood inhibited the production of interleukin-17 (IL-17)
      and interferon-gamma (IFNgamma) in a dose-dependent manner, affecting both
      proliferation and transcription, but had no effect on IL-6 and IL-8 production.
      Tofacitinib did not affect IL-6 and IL-8 production by RASFs and CD14+ monocytes.
      However, conditioned medium from CD4+ T cells cultured with tofacitinib inhibited
      IL-6 production by RASFs and IL-8 production by CD14+ monocytes. Treatment of
      SCID-HuRAg mice with tofacitinib decreased serum levels of human IL-6 and IL-8
      and markedly suppressed invasion of synovial tissue into cartilage. CONCLUSION:
      Tofacitinib directly suppressed the production of IL-17 and IFNgamma and the
      proliferation of CD4+ T cells, resulting in inhibition of IL-6 production by
      RASFs and IL-8 production by CD14+ cells and decreased cartilage destruction. In
      CD4+ T cells, presumably Th1 and Th17 cells, JAK plays a crucial role in RA
      synovitis.

PMID- 22147634
TI  - Human mesenchymal stem cells in synovial fluid increase in the knee with
      degenerated cartilage and osteoarthritis.
AB  - We investigated whether mesenchymal stem cells (MSCs) in synovial fluid (SF)
      increased in the knee with degenerated cartilage and osteoarthritis. SF was
      obtained from the knee joints of 22 patients with anterior cruciate ligament
      (ACL) injury during ACL reconstruction, and cartilage degeneration was evaluated
      arthroscopically. SF was also obtained from the knee joints of 6 healthy
      volunteers, 20 patients with mild osteoarthritis, and 26 patients with severe
      osteoarthritis, in which the grading was evaluated radiographically. The cell
      component in the SF was cultured for analyses. Synovium (SYN) and bone marrow
      (BM) were also harvested during total knee arthroplasties. The MSC number in SF
      was correlated with the cartilage degeneration score evaluated by arthroscopy.
      The MSC number in the SF was hardly noticed in normal volunteers, but it
      increased in accordance with the grading of osteoarthritis. Though no significant
      differences were observed regarding surface epitopes, or differentiation
      potentials, the morphology and gene profiles in SF MSCs were more similar to
      those in SYN MSCs than in BM MSCs. We listed 20 genes which were expressed higher
      in both SYN MSCs and SF MSCs than in BM MSCs, and 3 genes were confirmed by
      quantitative RT-PCR. MSCs in SF increased along with degenerated cartilage and
      osteoarthritis.

PMID- 22147635
TI  - Neuroblastoma obeys "The Law of Small Numbers".

PMID- 22147636
TI  - Plasmon-enhanced photocatalytic activity of iron oxide on gold nanopillars.
AB  - Photocatalytic water splitting represents a promising way to produce renewable
      hydrogen fuel from solar energy. Ultrathin semiconductor electrodes for water
      splitting are of particular interest because the optical absorption occurs in the
      region where photogenerated charge carriers can effectively contribute to the
      chemical reactions on the surface. It is therefore important to manipulate and
      concentrate the incident light so that more photons can be absorbed within the
      thin film. Here we show an enhanced photocurrent in a thin-film iron oxide
      photoanode coated on arrays of Au nanopillars. The enhancement can be attributed
      primarily to the increased optical absorption originating from both surface
      plasmon resonances and photonic-mode light trapping in the nanostructured
      topography. The resonances can be tuned to a desirable wavelength by varying the
      thickness of the iron oxide layer. A net enhancement as high as 50% was observed
      over the solar spectrum.

PMID- 22147637
TI  - Major Australian tropical fruits biodiversity: bioactive compounds and their
      bioactivities.
AB  - The plant kingdom harbours many diverse bioactive molecules of pharmacological
      relevance. Temperate fruits and vegetables have been highly studied in this
      regard, but there have been fewer studies of fruits and vegetables from the
      tropics. As global consumers demand and are prepared to pay for new appealing and
      exotic foods, tropical fruits are now being more intensively investigated.
      Polyphenols and major classes of compounds like flavonoids or carotenoids are
      ubiquitously present in these fruits, as they are in the temperate ones, but
      particular classes of compounds are unique to tropical fruits and other plant
      parts. Bioactivity studies of compounds specific to tropical fruit plants may
      lead to new drug discoveries, while the synergistic action of the wide range of
      diverse compounds contained in plant extracts underlies nutritional and health
      properties of tropical fruits and vegetables. The evidence for in vitro and
      animal bioactivities is a strong indicator of the pharmacological promise shown
      in tropical fruit plant biodiversity. In this review, we will discuss both the
      occurrence of potential bioactive compounds isolated and identified from a
      selection of tropical fruit plants of importance in Australia, as well as recent
      studies of bioactivity associated with such fruits and other fruit plant parts.

PMID- 22147638
TI  - Acceptance of 2009 H1N1 influenza vaccine among pregnant women in Delaware.
AB  - Due to disproportionately high mortality from 2009 H1N1 influenza, pregnant women
      were given highest priority for H1N1 vaccination. We surveyed postpartum women to
      determine vaccine uptake and reasons for lack of vaccination. We performed a
      cross-sectional survey of postpartum women delivering at our institution from
      February 1 to April 15, 2010. The 12-question survey ascertained maternal
      characteristics and vaccination concerns. Among 307 postpartum women, 191 (62%)
      had received H1N1 vaccination and 98 (32%) had declined. Factors associated with
      H1N1 vaccination included older age (relative risk [RR] 1.3, 95% confidence
      interval [CI] 1.1 to 1.5 for age >=35 years compared with 20 to 34 years), at
      least college education (RR 1.5, 95% CI 1.3 to 1.8), prior influenza vaccination
      (RR 1.6, 95% CI 1.3 to 2.0), provider recommendation (RR 3.9, 95% CI 2.1 to 7.4),
      vaccination of family members (RR 1.6, 95% CI 1.3 to 1.9), and receipt of
      seasonal influenza vaccination (RR 2.2, 95% CI 1.7 to 2.9). Non-Hispanic black
      women were less likely to have been vaccinated (RR 0.6, 95% CI 0.5 to 0.8) than
      non-Hispanic white women. Safety concerns were cited by the majority (66%) of
      nonvaccinated women. H1N1 vaccine uptake among pregnant women was substantially
      higher than reported influenza vaccination rates during previous seasons. Safety
      concerns were the major barrier to vaccination.

PMID- 22147639
TI  - Twenty-four-hour ambulatory blood pressure monitor heart rate: a potential marker
      for gestational hypertension in at-risk women.
AB  - We prospectively correlated the 24-hour ambulatory blood pressure measurements
      (ABPM) to conventional sphygmomanometer blood pressure measurements (CSM) in
      women at risk for gestational hypertensive disorders (GHTNDs) and identified
      predictive factors from ABPM for GHTND. We analyzed 73 women with >= 1 risk
      factor for developing a GHTND. Using both the CSM and ABPM, the systolic blood
      pressure, diastolic blood pressure, mean arterial pressure (MAP), and heart rate
      (HR) were measured for 24 hours during three periods (14 to 24 weeks; 24 to 32
      weeks; and 33 weeks to delivery). Correlation between the CSM and ABPM lessened
      as pregnancy progressed. Seventeen (25%) of women developed a GHTND. MAP
      variability increased in the GHTND group versus those without a GHTND. The odds
      of developing a GHTND increased 1.5 times for every 1 beat per minute increase in
      the ABPM 24-hour HR at visit 1 and reversed by visit 3. In women at risk for a
      GHTND, CSM and ABPM correlate less well as pregnancy advances. HR changes in at
      risk women may be a marker for the development of a GHTND and may reflect
      increased sympathetic activity and/or decreased baroreceptor sensitivity.

PMID- 22147640
TI  - Hydrographic magnetic resonance imaging of the fetal eye.
AB  - Previous work has shown that fetal hydrographic magnetic resonance imaging (MRI)
      provided additional information complementary to T2-weighted single-shot fast
      spin echo (ssFSE) images. The objective of this study was to determine if
      hydrographic MRI provides better conspicuity of fetal eye structures compared
      with ssFSE MRI. ssFSE and hydrographic images were retrospectively examined in 82
      consecutive fetal studies with normal central nervous system without sensitivity
      encoding. Relative signal intensity values on ssFSE and hydrographic MRI were
      obtained for vitreous and sclera. Ratios of the signal intensity of vitreous to
      the signal intensity of sclera were calculated to determine conspicuity. Similar
      measurements were obtained in a smaller separate data set (n = 41) using
      hydrographic imaging with sensitivity encoding techniques. The hydrographic
      images significantly demonstrated greater conspicuity (ratio of vitreous to
      sclera) than ssFSE images. This was consistent for both sensitivity encoding and
      no-sensitivity encoding groups. The difference in conspicuity was on average
      approximately two times greater in the hydrographic images compared with ssFSE
      images. Hydrographic MRI of the fetal eye provides on average two times greater
      conspicuity of fetal eye structures than ssFSE imaging. This enhancement is not
      affected by gestational age or the use of sensitivity encoding parallel imaging
      techniques.

PMID- 22147641
TI  - Chorioamnionitis and chronic lung disease of prematurity: a path analysis of
      causality.
AB  - Current evidence suggests that additional pathogenetic factors could play a role
      in the development of chronic lung disease of prematurity, other than mechanical
      ventilation and free radical injury. The introduction of the concept of "fetal
      inflammatory response syndrome" offers a new perspective on the pathogenesis of
      chronic lung disease of prematurity. New statistical approaches could be useful
      tools in evaluating causal relationships in the development of chronic morbidity
      in preterm infants. The aim of this study was to test a new statistical framework
      incorporating path analysis to evaluate causality between exposure to
      chorioamnionitis and fetal inflammatory response syndrome and the development of
      chronic lung disease of prematurity. We designed a prospective cohort study that
      included consecutively born premature infants less than 32 weeks of gestation
      whose placentas were collected for histological analysis. Histological
      chorioamnionitis, clinical data, and neonatal outcomes were related to chronic
      lung disease. Along with standard statistical methods, a path analysis was
      performed to test the relationship between histological chorioamnionitis,
      gestational age, mechanical ventilation, and development of chronic lung disease
      of prematurity. Among the newborns enrolled in the study, 69/189 (36%) had
      histological chorioamnionitis. Of those with histological chorioamnionitis, 28/69
      (37%) were classified as having fetal inflammatory response syndrome, according
      to the presence of severe chorioamnionitis and funisitis. Histological
      chorioamnionitis was associated with a lower birth weight, shorter gestation,
      higher frequency of patent ductus arteriosus, greater use of surfactant, and
      higher frequency of chronic lung disease of prematurity. Severe chorioamnionitis
      and funisitis were significantly associated with lower birth weight, lower
      gestational age, lower Apgar score at 5 minutes, more frequent use of mechanical
      ventilatory support and surfactant, as well as higher frequency of patent ductus
      arteriosus and chronic lung disease. The results of the path analysis showed that
      fetal inflammatory response syndrome has a significant direct (0.66), indirect
      (0.11), and overall (0.77) effect on chronic lung disease. This study
      demonstrated a strong positive correlation between exposure of the fetus to a
      severe inflammatory response and the development of chronic lung disease of
      prematurity.

PMID- 22147642
TI  - Poly(3-hydroxybutyrate) production by Bacillus cereus SPV using sugarcane
      molasses as the main carbon source.
AB  - The main hindrance in the use of polyhydroxyalkanoates (PHAs) as a replacement
      for existing petroleum-based plastics is their high production cost. The carbon
      source accounts for 50% of the cost for PHA production. Thus, increasing the
      yield and productivity of PHAs on cheap substrates is an important challenge for
      biotechnologists to support the commercialization and further applications of
      these polymers. In this study, we have investigated the use of an agricultural
      raw material, sugarcane molasses, as the main carbon source for poly(3
      hydroxybutyrate) (P(3HB)) production by Bacillus cereus SPV. These studies were
      carried out in both shaken flasks and 2 L bioreactors. Various conditions were
      evaluated for their effects on biomass and P(3HB) accumulation. A high polymer
      yield was obtained, 61.07% dry cell weight (DCW) in a 1 L shaken flask study and
      51.37% DCW in a 2 L fermenter study. These yields are 50% higher than previously
      observed with Bacillus cereus SPV. Hence, the results are encouraging and show
      that sugarcane molasses are a promising carbon source for an economical and
      commercially viable production of P(3HB).

PMID- 22147643
TI  - A comparison between complete immobilisation and protected active mobilisation in
      sensory nerve recovery following isolated digital nerve injury.
AB  - Post-operative immobilisation following isolated digital nerve repair remains a
      controversial issue amongst the microsurgical community. Protocols differ from
      unit to unit and even, as evidenced in our unit, may differ from consultant to
      consultant. We undertook a retrospective review of 46 patients who underwent
      isolated digital nerve repair over a 6-month period. Follow-up ranged from 6 to
      18 months. Twenty-four were managed with protected active mobilisation over a 4
      week period while 22 were immobilised over the same period. Outcomes such as
      return to work, cold intolerance, two-point discrimination and temperature
      differentiation were used as indicators of clinical recovery. Our results showed
      that there was no significant difference noted in either clinical assessment of
      recovery or return to work following either post-operative protocol, suggesting
      that either regime may be adopted, tailored to the patient's needs and resources
      of the unit.

PMID- 22147644
TI  - Special theme issue on advances in education in anesthesiology.

PMID- 22147645
TI  - Facing unexpected reactivity paths with Zr(IV)-pyridylamido polymerization
      catalysts.
AB  - This work provides original insights to the better understanding of the complex
      structure-activity relationship of Zr(IV)-pyridylamido-based olefin
      polymerization catalysts and highlights the importance of the metal-precursor
      choice (Zr(NMe(2))(4) vs. Zr(Bn)(4)) to prepare precatalysts of unambiguous
      identity. A temperature-controlled and reversible sigma-bond
      metathesis/protonolysis reaction is found to take place on the Zr(IV)-amido
      complexes in the 298-383 K temperature range, changing the metal coordination
      sphere dramatically (from a five-coordinated tris-amido species stabilized by
      bidentate monoanionic {N,N(-)} ligands to a six-coordinated bis-amido-mono-amino
      complexes featured by tridentate dianionic {N(-),N,C(-)} ligands). Well-defined
      neutral Zr(IV)-pyridylamido complexes have been prepared from Zr(Bn)(4) as metal
      source. Their cationic derivatives [Zr(IV) N(-),N,C(-)}Bn](+)[B(C(6)F(5))(4)](-)
      have been successfully applied to the room-temperature polymerization of 1-hexene
      with productivities up to one order of magnitude higher than those reported for
      the related Hf(IV) state-of-the-art systems. Most importantly, a linear increase
      of the poly(1-hexene) M(n) values (30-250 kg mol(-1)) has been observed upon
      catalyst aging. According to that, the major active species (responsible for the
      increased M(n) polymer values) in the aged catalyst solution, has been
      identified.

PMID- 22147646
TI  - 'Open Window': a randomized trial of the effect of new media art using a virtual
      window on quality of life in patients' experiencing stem cell transplantation.
AB  - OBJECTIVES: To measure the psychological effect of an art intervention on
      hospitalized patients and explore benefits to their quality of life. METHODS: We
      conducted a large prospective randomized trial between July 2006 and August 2009
      of an art intervention, Open Window (OW), in patients undergoing stem cell
      transplantation for a hematological malignancy compared with a control group. The
      primary endpoint measured the effect of an art intervention on levels of anxiety,
      depression, and stress using the Hospital Anxiety and Depression Scale and the
      Distress Thermometer. The secondary endpoint measured the influence of OW on
      patients' experiences of stem cell transplantation using the OW survey and
      expectations questionnaires. RESULTS: Of the 199 patients in the study, 96 were
      randomized to the intervention group and 103 to the control group. Participants
      in the intervention group had significantly reduced levels of anxiety on the day
      before transplant (p = 0.001), at day 7 (p = 0.041), and day 60 (p = 0.035).
      There was a significant reduction in depression before transplant (p = 0.022).
      Participants in the intervention group reported better experiences (p < 0.005).
      Qualitative data showed that those in the intervention group commented freely on
      their likes and dislikes about OW and how it made them feel. CONCLUSION: An art
      intervention, OW, had a positive influence on health-related quality of life and
      patients' experiences of having a stem cell transplant.

PMID- 22147647
TI  - Pro-opiomelanocortin gene delivery suppresses the growth of established Lewis
      lung carcinoma through a melanocortin-1 receptor-independent pathway.
AB  - BACKGROUND: Pro-opiomelanocortin (POMC) is the precursor of several
      neuropeptides, such as corticotropin, melanocyte-stimulating hormone and the
      endogenous opioid (beta-endorphin). Our previous studies have indicated that POMC
      gene delivery inhibited the progression and metastasis of B16-F10 melanoma via
      the alpha- melanocyte-stimulating hormone/melanortin-1 receptor (MC-1R) pathway.
      METHODS: In the present study, the therapeutic efficacy of POMC gene therapy was
      evaluated in mice bearing established Lewis lung carcinoma (LLC) models both in
      vitro and in vivo. We also investigated the MC-1R-independent mechanism
      underlying POMC gene therapy. RESULTS: We found that POMC gene delivery
      significantly inhibited the growth and colony formation in MC-1R-deficient LLC
      cells. In addition, POMC gene transfer effectively suppressed the growth of
      established LLC in mice. The inhibitory mechanisms underlying POMC gene delivery
      were attibuted to be inhibition of proliferation and the induction of apoptosis.
      Moreover, POMC gene delivery attenuated tumor beta-catenin signaling by reducing
      protein levels of beta-catenin and its downstream proto-oncogenes, including
      cyclin D1 and c-myc. Lastly, POMC gene delivery induced a significant suppression
      of tumor vasculature. CONCLUSIONS: These results support the existence of an MC
      1R-independent pathway for POMC gene therapy, which further expands the
      therapeutic spectrum of POMC therapy for multiple types of cancer.

PMID- 22147650
TI  - Prion proteins (PRNP and PRND) are over-expressed in osteosarcoma.
AB  - Although osteosarcoma is the most common bone malignancy, the molecular and
      cellular mechanisms influencing its pathogenesis have remained elusive. Prion
      proteins (PRNP and PRND), known mostly for its involvement in neurodegenerative
      spongiform encephalopathies, have been recently demonstrated to be involved in
      resistance to apoptosis, tumorigenesis, proliferation, and metastasis. The main
      aim of research was to study whether prion proteins were over-expressed in human
      osteosarcoma, and if prion proteins could have a role also in osteosarcomas. We
      evaluated differential gene expression between 22 cases of osteosarcoma and 40
      cases of normal bone specimens through cDNA microarray analysis spanning a
      substantial fraction of the human genome. PRNP and PRND are significantly over
      expressed in osteosarcoma. PRNP and PRND appear involved with some important
      genes related to tumorigenesis and apoptosis. PRNP is linked to PTK2, RBBP9, and
      TGFB1 while PRND is linked to TNFSF10, BCL2A1, NFKB2, and TP53RK. Increased
      expression on Affymetrix arrays of prion proteins seems to be associated with the
      development of osteosarcoma. Prions seem to induce a negative regulation of
      apoptosis, thus promoting osteosarcoma development and progression. Osteosarcoma
      is a very aggressive tumor and even after modern chemotherapy and excision of
      tumors efforts are needed to improve clinical outcome. Since Prion proteins seem
      to be related to osteosarcoma development, their inhibition could represent a new
      approach to the molecular treatment of osteosarcoma.

PMID- 22147649
TI  - A phase II, randomized, double-blind, placebo-controlled study evaluating the
      efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody,
      in combination with methotrexate in patients with rheumatoid arthritis.
AB  - OBJECTIVE: CXCL10 (also known as interferon-gamma-inducible 10-kd protein [IP
      10]) is a chemokine that potentially plays a role in the immunopathogenesis of
      rheumatoid arthritis (RA). We undertook this phase II study to evaluate the
      efficacy and safety of MDX-1100, a fully human, anti-CXCL10 (anti-IP-10)
      monoclonal antibody, in RA patients whose disease responded inadequately to
      methotrexate (MTX). METHODS: Patients with active RA receiving stable doses of
      MTX (10-25 mg weekly) were randomized to receive intravenous doses of 10 mg/kg
      MDX-1100 (n = 35) or placebo (n = 35) every other week. The primary end point was
      the proportion of patients meeting the American College of Rheumatology 20%
      improvement criteria (achieving an ACR20 response) on day 85, and patients were
      followed up for safety to day 141. RESULTS: The ACR20 response rate was
      significantly higher among MDX-1100-treated patients than among placebo-treated
      patients (54% versus 17%; P = 0.0024). Statistically significant differences in
      the ACR20 response rate between treatments were observed starting on day 43 (P <
      0.05). The ACR50 and ACR70 response rates on day 85 did not differ between the
      groups. Overall, 51.4% of MDX-1100-treated patients and 30.3% of placebo-treated
      patients experienced at least 1 adverse event (AE). No study drug-related serious
      AEs were reported. CONCLUSION: MDX-1100 was well tolerated and demonstrated
      clinical efficacy in RA patients whose disease responded inadequately to MTX.
      This is the first study to demonstrate clinical efficacy of a chemokine inhibitor
      in RA and supports the notion of a potential role of IP-10 in the
      immunopathogenesis of RA.

PMID- 22147648
TI  - Cardiac output monitoring devices: an analytic review.
AB  - To evaluate cardiac output (CO), both invasive and semi-invasive monitors are
      used in critical care medicine. The pulmonary artery catheter is an invasive tool
      to assess CO with the major criticism that the level of its invasiveness is not
      supported by an improvement in patients' outcomes. The interest in a lesser
      invasive techniques is high. Therefore, alternative techniques have been
      developed recently, and are used frequently in critical care medicine. Cardiac
      output can be monitored continuously by different devices that analyze the stroke
      volume and CO. The purpose of this review is to understand these new technologies
      and their applications and limitations.

PMID- 22147651
TI  - Paroxysmal nocturnal hemoglobinuria in pediatric patients.
AB  - BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease in
      children. The most significant clinical features of PNH include: bone marrow
      failure, intravascular hemolysis, and thrombosis. To further characterize the
      clinical presentation and outcome to treatment we performed a retrospective
      analysis of pediatric patients with PNH. PROCEDURE: We reviewed the medical
      records of 12 consecutive pediatric patients with PNH diagnosed at our
      institution from 1992 to 2010. RESULTS: Presenting clinical symptoms included:
      bone marrow failure (N = 10); gross hemoglobinuria with isolated red cell anemia
      (N = 1); and jaundice, hepatitis, and isolated thrombocytopenia (N = 1).
      Immunosuppressive therapy was the initial treatment for 8 patients. Five patients
      had myelodysplastic features without developing excessive blasts or leukemic
      transformation. Thrombosis occurred in 6 patients. Five patients underwent
      hematopoietic stem cell transplant (HSCT) of whom 3 patients are alive and
      disease-free. Three patients received anti-complement therapy with eculizumab.
      Two patients died following complications related to thrombosis and 2 patients
      are transfusion independent with stable disease. CONCLUSION: This report
      highlights a high rate of bone marrow failure along with a low rate of
      hemoglobinuria at presentation, a high rate of thrombosis, and for some patients
      the spontaneous resolution of myelodysplastic features. Delay in diagnosis is
      common and we recommend appropriate PNH testing in all patients with AA, MDS,
      unexplained Coombs-negative hemolysis, or thrombosis. While HSCT remains the only
      curative option the high prevalence of hemolysis and thrombosis should warrant
      the consideration of early treatment with anti-complement therapy.

PMID- 22147652
TI  - Temporoparietal fascia free flap for pharyngeal coverage after salvage total
      laryngectomy.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to assess whether the use of the
      temporoparietal fascia as a free flap for pharyngeal closure reinforcement
      reduced the incidence of pharyngocutaneous fistula (PCF) in the salvage setting.
      STUDY DESIGN: Consecutive case series. METHODS: After research ethics board
      approval, 12 patients who required salvage laryngectomy, including reinforcement
      coverage of the primarily closed pharyngeal defect with temporoparietal fascia as
      a free tissue transfer, were analyzed. RESULTS: One (8%) out of 12 patients
      experienced pharyngocutaneous fistula that responded with conservative wound
      packing. CONCLUSIONS: The PCF rate of 8% is significantly better than in similar
      salvage cases without flap coverage. Moreover, our PCF rate is comparable to the
      results shown for the pectoralis major muscle flap. The most obvious benefit of
      the temporoparietal fascia free flap for pharyngeal coverage in salvage
      laryngectomy is a reduced PCF rate with diminished donor-site morbidity,
      including cosmetic outcome, shoulder girdle function, and chest deformity.

PMID- 22147653
TI  - Multi-parametric approach to identify coffee components that regulate mechanisms
      of gastric acid secretion.
AB  - SCOPE: Chlorogenic acid (CA), caffeine (CAFF), pyrogallol (PYR), catechol (CAT),
      (beta)N-alkanoyl-hydroxytryptamides (C5HT) and N-methylpyridinium (N-MP) were
      evaluated for their influence on mechanisms of gastric acid secretion as single
      compounds and in biomimetic mixtures. METHODS AND RESULTS: Compounds were tested
      in coffee representative concentrations. Human gastric cancer cells (HGT-1) were
      used to study the proton secretory activity by Ussing chamber experiments and
      FACS analysis. For activation of EGFr, Akt1, ERK1/2, ATF-2 and cAMP levels, we
      performed pathway screening assays. Time-dependent expression of related genes
      were determined by real-time PCR. Part of the data was used for neural network
      modeling to identify the most relevant compounds. N-MP increased the expression
      of the anti-secretory somatostatin receptor by 114%, whereas C5HT decreased its
      expression by 52%. N-MP down-regulated the pro-secretory CHRM3 receptor by 36%
      and the H+,K+-ATPase by 36%. CAFF stimulated the secretory activity in the
      functional assays, whereas N-MP and CA decreased proton secretion. After applying
      a pathway analysis, we were able to discriminate between CAFF, CA, CAT, C5HT, PYR
      and histamine-activating EGFr signaling and N-MP-associated ERK1/2 signaling.
      CONCLUSION: By applying a multi-parametric approach, N-MP was shown to
      effectively down-regulate mechanisms of gastric acid secretion in human parietal
      gastric cells.

PMID- 22147654
TI  - Microarray expression profiling identifies genes regulating sustained cell
      specific productivity (S-Qp) in CHO K1 production cell lines.
AB  - Fed batch culture processes are often characterized by decreasing cell culture
      performance as the process continues, presumably through the depletion of vital
      nutrients and the accumulation of toxic byproducts. We have similarly observed
      that cellular productivity (Qp) often declines during the course of a fed batch
      process; however, it is not clear why some cell lines elicit this behavior, while
      others do not. We here present a transcriptomic profiling analysis of a phenotype
      of sustained Qp (S-Qp) in production Chinese hamster ovary (CHO) culture, in
      which a marked drop in Qp levels ("non-sustained" (NS) phenotype) in two cell
      lines irrespective of viability levels was compared to two cell lines that
      consistently displayed high Qp throughout the culture ("sustained" (S)
      phenotype). Statistical analysis of the microarray data resulted in the
      identification of 22 gene transcripts whose expression patterns were either
      significantly negatively or positively correlated with long-term maintenance of
      Qp over the culture lifespan. qPCR analysis of four of these genes on one of each
      (NS2, S2) of the cell lines examined by microarray analysis confirmed that two
      genes (CRYAB and MGST1) both replicated the microarray results and were
      differentially regulated between the NS and S phenotypes.

PMID- 22147655
TI  - Factors affecting the aldosterone/renin ratio.
AB  - Although the aldosterone/renin ratio (ARR) is the most reliable screening test
      for primary aldo-steronism, false positives and negatives occur. Dietary salt
      restriction, concomitant malignant or renovascular hypertension, pregnancy and
      treatment with diuretics (including spironolactone), dihydropyridine calcium
      blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor
      antagonists can produce false negatives by stimulating renin. We recently
      reported selective serotonin reuptake inhibitors lower the ratio. Because
      potassium regulates aldosterone, uncorrected hypokalemia can lead to false
      negatives. Beta-blockers, alpha-methyldopa, clonidine, and nonsteroidal anti
      inflammatory drugs suppress renin, raising the ARR with potential for false
      positives. False positives may occur in patients with renal dysfunction or
      advancing age. We recently showed that (1) females have higher ratios than males,
      and (2) false positive ratios can occur during the luteal menstrual phase and
      while taking an oral ethynylestradiol/drospirenone (but not implanted subdermal
      etonogestrel) contraceptive, but only if calculated using direct renin
      concentration and not plasma renin activity. Where feasible, diuretics should be
      ceased at least 6 weeks and other interfering medications at least 2 before ARR
      measurement, substituting noninterfering agents (e. g., verapamil slow-release+/
      hydralazine and prazosin or doxazosin) were required. Hypokalemia should be
      corrected and a liberal salt diet encouraged. Collecting blood midmorning from
      seated patients following 2-4 h upright posture improves sensitivity. The ARR is
      a screening test only and should be repeated once or more before deciding whether
      to proceed to confirmatory suppression testing. Liquid chromatography-tandem mass
      spectrometry aldosterone assays represent a major advance towards addressing
      inaccuracies inherent in other available methods.

PMID- 22147656
TI  - Diabetic lipoproteins and adrenal aldosterone synthesis--a possible
      pathophysiological link?
AB  - An increased prevalence of diabetes mellitus (DM) has been reported in patients
      with primary aldosteronism (PA). DM is associated with abnormal structure and
      metabolism of circulating lipoproteins, which normally serve as a major source of
      cholesterol for adrenocortical steroidogenesis. The present study has been
      designed to investigate the effect of diabetically modified lipoproteins on
      adrenocortical aldosterone synthesis. Lipoproteins (VLDL, LDL, HDL) isolated from
      healthy volunteers, were subjected to oxidation or glycoxidation in the presence
      of sodium hypochlorite (3 mmol/l) or glucose (200 mmol/l), and aldosterone
      synthesis in human adrenocortical cells (H295R) was examined. Native and
      glycoxidized VLDL had greatest stimulatory effect on aldosterone production by 15
      fold and 14-fold, respectively. At the molecular level, these VLDL produced
      maximum increases in Cyp11B2 mRNA level up to 17-fold. Experiments with the
      highly selective scavenger receptor class B type I (SR-BI) inhibitor BLT-1
      revealed that cholesterol uptake from native and glycoxidized HDL and VLDL for
      hormone production is considerably mediated by SR-BI. Western blot analysis of
      extracellular signal-regulated kinase (ERK 1/2) phosphorylation and experiments
      with the MEK inhibitor U0126 indicated a specific mechanistic role of the ERK
      cascade in lipoprotein-mediated steroid hormone release. In summary, diabetic
      dyslipidemia and modification of circulating lipoproteins may promote
      adrenocortical aldosterone synthesis.

PMID- 22147657
TI  - Plasma glucose-lowering action of allantoin is induced by activation of
      imidazoline I-2 receptors in streptozotocin-induced diabetic rats.
AB  - Allantoin, an active principle of yam, is documented to lower plasma glucose in
      diabetic rats. However, action mechanisms of allantoin remain obscure. It has
      been indicated that metformin shows ability to activate imidazoline I-2 receptors
      (I-2R) to lower blood sugar. Allantoin has also a chemical structure similar to
      metformin; both belong to guanidinium derivative. Thus, it is of special interest
      to know the effect of allantoin on I-2R. In the present study, the marked plasma
      glucose-lowering action of allantoin in streptozotocin-induced type-1 like
      diabetic rats was blocked by specific I-2R antagonist, BU224, in a dose-dependent
      manner. Also, the increase of beta-endorphin release by allantoin was blocked by
      BU224 in the same manner. Otherwise, amiloride at the dose sufficient to block I
      2AR abolished the allantoin-induced beta-endorphin release and inhibited the
      blood glucose-lowering action of allantoin markedly but not completely. The
      direct effect of allantoin on glucose uptake in isolated skeletal muscle was also
      blocked by BU224. Also, the phosphorylation of AMPK in isolated skeletal muscle
      was raised by allantoin in a concentration-dependent manner. More-over, insulin
      sensitivity in diabetic rats was markedly increased by allantoin and this action
      was also blocked by BU224. These results suggest that allantoin has an ability to
      activate imidazoline I-2R while I-2AR is linked to the increase of beta-endorphin
      release and I-2BR is related to other actions including the influence in skeletal
      muscle for lowering of blood glucose in type-1 like diabetic rats. Thus,
      allantoin can be developed to treat diabetic disorders in the future.

PMID- 22147658
TI  - Non-USH2A mutations in USH2 patients.
AB  - We have systematically analyzed the two known minor genes involved in Usher
      syndrome type 2, DFNB31 and GPR98, for mutations in a cohort of 31 patients not
      linked to USH2A. PDZD7, an Usher syndrome type 2 (USH2) related gene, was
      analyzed when indicated. We found that mutations in GPR98 contribute
      significantly to USH2. We report 17 mutations in 10 individuals, doubling the
      number of GPR98 mutations reported to date. In contrast to mutations in usherin,
      the mutational spectrum of GPR98 predominantly results in a truncated protein
      product. This is true even when the mutation affects splicing, and we have
      incorporated a splicing reporter minigene assay to show this, where appropriate.
      Only two mutations were found which we believe to be genuine missense changes.
      Discrepancy in the mutational spectrum between GPR98 and USH2A is discussed. Only
      two patients were found with mutations in DFNB31, showing that mutations of this
      gene contribute to only a very small extent to USH2. Close examination of the
      clinical details, where available, for patients in whom no mutation was found in
      USH2A, GPR98, or DFNB31, showed that most of them had atypical features. In
      effect, these three genes account for the vast majority of USH2 patients and
      their analysis provide a robust pathway for routine molecular diagnosis.

PMID- 22147659
TI  - Air-stable platinum and palladium complexes featuring bis[2,4
      bis(trifluoromethyl)phenyl]phosphinous acid ligands.
AB  - Secondary phosphane oxides, R(2)P(O)H, are commonly used as preligands for
      transition-metal complexes of phosphinous acids, R(2)P-OH (R=alkyl, aryl), which
      are relevant as efficient catalysts in cross-coupling processes. In contrast to
      previous work by other groups, we are interested in the ligating properties of an
      electron-deficient phosphinous acid, (R(f))(2)P-OH, bearing the strongly electron
      withdrawing and sterically demanding 2,4-bis(trifluoromethyl)phenyl group towards
      catalysis-relevant metals, such as palladium and platinum. The preligand bis[2,4
      bis(trifluoromethyl)phenyl]phosphane oxide, (R(f))(2)P(O)H, reacts smoothly with
      solid platinum(II) dichloride yielding the trans-configured phosphinous acid
      platinum complex trans-[PtCl(2)({2,4-(CF(3))(2)C(6)H(3)}(2)POH)(2)]. The
      deprotonation of one phosphinous acid ligand with an appropriate base leads to
      the cis-configured monoanion complex cis-[PtCl(2)({2,4
      (CF(3))(2)C(6)H(3)}(2)PO)(2)H](-), featuring the quasi-chelating phosphinous acid
      phosphinito unit, (R(f))(2)P-O-H...O=P(R(f))(2), which exhibits a strong hydrogen
      bridge substantiated by an O...O distance of 245.1(4) pm. The second
      deprotonation step is accompanied by a rearrangement to afford the trans
      configured dianion trans-[PtCl(2)({2,4-(CF(3))(2)C(6)H(3)}(2)PO)(2)](2-). The
      reaction of (R(f))(2)P(O)H with solid palladium(II) dichloride initially yields a
      mononuclear palladium complex [PdCl(2)({2,4-(CF(3))(2)C(6)H(3)}(2)POH)(2)], which
      condenses under liberation of HCl to the neutral dinuclear palladium complex
      [Pd(2)(MU-Cl)(2){({2,4-(CF(3))(2)C(6)H(3)}(2)PO)(2)H}(2)]. The equilibrium
      between the mononuclear [PdCl(2)({2,4-(CF(3))(2)C(6)H(3)}(2)POH)(2)] and
      dinuclear [Pd(2)(MU-Cl)(2){({2,4-(CF(3))(2)C(6)H(3)}(2)PO)(2)H}(2)] palladium
      complexes is reversible and can be shifted in each direction by the addition of
      base or HCl, respectively. Treatment of palladium(II) hexafluoroacetylacetonate,
      [Pd(F(6)acac)(2)], with a slight excess of (R(f))(2)P(O)H yields the complex
      [Pd(F(6)acac)({2,4-(CF(3))(2)C(6)H(3)}(2)PO)(2)H]. The quasi-chelating
      phosphinous acid phosphinito unit, which is formed by the liberation of
      HF(6)acac, is characterized by a O...O distance of 244.1(3) pm. These transition
      metal complexes are stable towards air and moisture and can be stored for months
      without any evidence of decomposition.

PMID- 22147660
TI  - Characterisation of enzyme prodrug gene therapy combinations in coated spheroids
      and vascular networks in vitro.
AB  - BACKGROUND: Enzyme prodrug gene therapy is designed as a targeted cancer
      treatment, destroying gene-modified and bystander cells via exogenous enzyme
      generated cytotoxins. Targeting of tumour blood vessels using gene therapy is
      attractive, although optimal enzyme prodrug combinations have yet to be
      identified. METHODS: Seven enzyme prodrug combinations were ranked in two
      endothelial (HUVEC, HMEC-1) and one tumour cell line (T24) for their ability to
      reduce proliferation and viability. The ability to destroy bystander cells in two
      dimensions (2D) and three dimensions (3D), mode of cell kill, and the ability to
      disrupt vascular networks were measured. RESULTS: Endothelial cell proliferation
      (bromodeoxyuridine uptake) was reduced most effectively by Herpes simplex virus
      thymidine kinase (TK) with ganciclovir (GCV), followed by Escherichia coli
      nitroreductase NfsB (NTR) with CB1954; viability [3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay] was reduced most efficiently by NTR/CB1954
      followed by TK/GCV. Of the seven combinations, only NTR/CB1954 displayed
      measurable bystander effects in 2D monolayers, and none demonstrated bystander
      killing in coated spheroids, a 3D spatially distinct model with tissue-like cell
      density. NTR-expressing endothelial cells displayed increased apoptosis, necrosis
      and caspase-3 activity after CB1954 treatment. Despite good antiproliferative
      activity, TK/GCV was ineffective at disrupting vascular network-like structures
      of endothelial cells, whereas NTR/CB1954 was efficient. NTR/metronidazole and the
      vascular disrupting agent, combretastatin A-4 phosphate, were the only other
      effective agents. CONCLUSIONS: Collectively, these data demonstrate that
      cytotoxic rather than cytostatic activity is necessary for efficient vascular
      disruption in vitro, and bystander killing is not essential. We identify
      NTR/CB1954 and NTR/metronidazole as candidates for in vivo investigation of
      vascular-targeted gene therapy.

PMID- 22147661
TI  - A randomized controlled trial of rituximab for the treatment of severe
      cryoglobulinemic vasculitis.
AB  - OBJECTIVE: To conduct a long-term, prospective, randomized controlled trial
      evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or
      cryoglobulinemic vasculitis (CV). METHODS: Fifty-nine patients with CV and
      related skin ulcers, active glomerulonephritis, or refractory peripheral
      neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV)
      infection, treatment of the HCV infection with antiviral agents had previously
      failed or was not indicated. Patients were randomized to the non-RTX group (to
      receive conventional treatment, consisting of 1 of the following 3:
      glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX
      group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid
      dosage when possible, and with a second course of RTX at relapse). Patients in
      the non-RTX group who did not respond to treatment could be switched to the RTX
      group. Study duration was 24 months. RESULTS: Survival of treatment at 12 months
      (i.e., the proportion of patients who continued taking their initial therapy),
      the primary end point, was statistically higher in the RTX group (64.3% versus
      3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6
      months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P <
      0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment
      with RTX (from a mean +/- SD of 11.9 +/- 5.4 at baseline to 7.1 +/- 5.7 at month
      2; P < 0.001) up to month 24 (4.4 +/- 4.6; P < 0.0001). RTX appeared to be
      superior therapy for all 3 target organ manifestations, and it was as effective
      as conventional therapy. The median duration of response to RTX was 18 months.
      Overall, RTX treatment was well tolerated. CONCLUSION: RTX monotherapy represents
      a very good option for severe CV and can be maintained over the long term in most
      patients.

PMID- 22147662
TI  - Haploscope: a tool for the graphical display of haplotype structure in
      populations.
AB  - Patterns of linkage disequilibrium are often depicted pictorially by using tools
      that rely on visualizations of raw data or pairwise correlations among individual
      markers. Such approaches can fail to highlight some of the more interesting and
      complex features of haplotype structure. To enable natural visual comparisons of
      haplotype structure across subgroups of a population (e.g. isolated
      subpopulations or cases and controls), we propose an alternative visualization
      that provides a novel graphical representation of haplotype frequencies. We
      introduce Haploscope, a tool for visualizing the haplotype cluster frequencies
      that are produced by statistical models for population haplotype variation. We
      demonstrate the utility of our technique by examining haplotypes around the LCT
      gene, an example of recent positive selection, in samples from the Human Genome
      Diversity Panel. Haploscope, which has flexible options for annotation and
      inspection of haplotypes, is available for download at
      http://scheet.org/software.

PMID- 22147663
TI  - Gene polymorphisms of angiotensin-converting enzyme and angiotensin II type 1
      receptor among chronic kidney disease patients in a Chinese population.
AB  - Chronic kidney disease (CKD) is highly prevalent in Taiwan and an increasing
      number of patients are affected, with a high risk of progression to end-stage
      renal disease and huge medical expenses. It has been predicted that the presence
      of hypertension increases with decreasing renal function due to a decrease in
      sodium excretion and activation of the renin-angiotensin system (RAS). The aim of
      this study was to investigate the influence of genetic variants of the RAS gene
      on CKD. We performed a case control association study and genotyped 135 CKD
      patients and 270 healthy controls among Han Chinese in Taiwan. All subjects were
      genotyped for angiotensinogen (AGT-M235T, T174M, A-20C), angiotensin-I converting
      enzyme (ACE-A2350G) and angiotensin II type 1 receptor (AGTR1-A1166C, C573T, C
      521T) polymorphisms of RAS genes by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) analysis. Significant associations were
      observed in ACE-A2350G and AGTR1-C573T polymorphism between CKD patients and
      controls. In regard to ACE-A2350G, compared with the AA genotype the GG genotype
      protected against CKD (adjusted odds ratio [OR] = 0.34; p = 0.01). In regard to
      AGTR1-C573T, the CT genotype was a risk for CKD compared with the CC genotype
      (adjusted OR = 1.82; p = 0.03). We conclude that ACE-A2350G and AGTR1-C573T
      polymorphisms are likely candidate determinants of CKD.

PMID- 22147664
TI  - Treatment of hereditary hemorrhagic telangiectasia with submucosal and topical
      bevacizumab therapy.
AB  - OBJECTIVE/HYPOTHESIS: Bevacizumab delivered as a submucosal and topical
      intranasal therapy effectively controls hereditary hemorrhagic telangiectasia
      (HHT)-associated epistaxis. STUDY DESIGN: Prospective institutional review board
      approved study. METHODS: Between December 2009 and December 2010, 19 patients
      with HHT-associated epistaxis were treated with 100 mg of intranasal submucosal
      bevacizumab. Following treatment, patients were contacted monthly to report their
      epistaxis severity score (ESS) for 9 or more months after their initial
      treatment. If a patient had a significant increase in their ESS, they were
      offered treatment with 100 mg of topical bevacizumab, administered via a metered
      dose atomizer. All treatments were recorded. RESULTS: All 19 patients had a
      postinjection ESS documented through 9 months, whereas 17 patients had completed
      ESS data between months 10 and 12. Six of the 19 patients received eight
      additional 100 mg of topical bevacizumab treatments because they had an increase
      in their ESS. Results demonstrated a mean preinjection ESS of 8.12, with an ESS
      nadir of 2.00 reached at 2 months following submucosal injection (P < 0.0001).
      Over the following 12 months, the mean ESS steadily increased back to a maximum
      of 3.6 reached at 11 months following injection (P < .0001). CONCLUSIONS:
      Intranasal submucosal bevacizumab effectively treats HHT-associated epistaxis for
      up to 12 months following treatment.

PMID- 22147665
TI  - Identification of educational and infrastructural barriers to prompt antibiotic
      delivery in febrile neutropenia: a quality improvement initiative.
AB  - BACKGROUND: Antibiotic administration within 60 minutes of presentation for
      medical care may be used as a treatment target for febrile neutropenia (FN);
      however, anecdotal evidence suggests this target is often missed. Few studies
      have examined the prevalence or causes of delay. We describe the median time to
      antibiotic administration at our institution, predictors of delay, and barriers
      to prompt administration to inform quality improvement strategies. PROCEDURE: A
      random sample of 50 episodes of FN presenting to the emergency department (ED)
      between 2008 and 2009 were reviewed. Times between triage, MD assessment, lab
      results, and antibiotic administration were recorded. Patient and ED variables
      were examined as possible predictors of delay. In parallel, lean methodology was
      used to identify system inefficiencies. A trained moderator conducted group
      interviews with interdisciplinary representatives involved in the emergency care
      of neutropenic patients to identify process barriers to prompt antibiotics.
      RESULTS: The median time from triage to antibiotics was 216 minutes
      (interquartile range [IQR] = 151-274 minutes). The greatest delay occurred
      following the reporting of lab results (152 minutes, IQR = 84-210 minutes). Only
      fall season predicted a longer time to antibiotics (P = 0.03). The lean process
      identified unnecessary areas of delay between departments. CONCLUSIONS: Time to
      antibiotic administration exceeded 1 hour. The chart review and lean process
      suggested targets for educational and infrastructural interventions, including an
      ED pre-printed order sheet, targeted combined subspecialty education between
      emergency and hematology/oncology staff, and family education. A mixed
      methodology approach represents a model for improving process efficiency and
      meeting "best-practice" targets in medicine.

PMID- 22147666
TI  - Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome:
      association with plasma monounsaturated and n-3 polyunsaturated fatty acid levels
      and insulin resistance.
AB  - SCOPE: Several insulin receptor substrate-2 (IRS-2) polymorphisms have been
      studied in relation to insulin resistance and type 2 diabetes. To examine whether
      the genetic variability at the IRS-2 gene locus was associated with the degree of
      insulin resistance and plasma fatty acid levels in metabolic syndrome (MetS)
      subjects. METHODS AND RESULTS: Insulin sensitivity, insulin secretion, glucose
      effectiveness, plasma fatty acid composition and three IRS-2 tag-single
      nucleotide polymorphisms (SNPs) were determined in 452 MetS subjects. Among
      subjects with the lowest level of monounsaturated (MUFA) (below the median), the
      rs2289046 A/A genotype was associated with lower glucose effectiveness (p<0.038),
      higher fasting insulin concentrations (p<0.028) and higher HOMA IR (p<0.038) as
      compared to subjects carrying the minor G-allele (A/G and G/G). In contrast,
      among subjects with the highest level of MUFA (above the median), the A/A
      genotype was associated with lower fasting insulin concentrations and HOMA-IR,
      whereas individuals carrying the G allele and with the highest level of omega-3
      polyunsaturated fatty acids (above the median) showed lower fasting insulin
      (p<0.01) and HOMA-IR (p<0.02) as compared with A/A subjects. CONCLUSION: The
      rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity
      by interacting with certain plasma fatty acids in MetS subjects.

PMID- 22147667
TI  - Graphene plasmon waveguiding and hybridization in individual and paired
      nanoribbons.
AB  - Plasmons in doped graphene exhibit relatively large confinement and long lifetime
      compared to noble-metal plasmons. Here, we study the propagation properties of
      plasmons guided along individual and interacting graphene nanoribbons. Besides
      their tunability via electrostatic gating, an additional handle to control these
      excitations is provided by the dielectric environment and the relative
      arrangement of the interacting waveguides. Plasmon interaction and hybridization
      in pairs of neighboring aligned ribbons are shown to be strong enough to produce
      dramatic modifications in the plasmon field profiles. We introduce a universal
      scaling law that considerably simplifies the analysis an understanding of these
      plasmons. Our work provides the building blocks to construct graphene plasmon
      circuits for future compact plasmon devices with potential application to optical
      signal processing, infrared sensing, and quantum information technology.

PMID- 22147668
TI  - Triclabendazole: an intriguing case of co-existence of conformational and
      tautomeric polymorphism.
AB  - The crystal polymorphism of the anthelmintic drug, triclabendazole (TCB), is
      described. Two anhydrates (Forms I and II), three solvates, and an amorphous form
      have been previously mentioned. This study reports the crystal structures of
      Forms I (1) and II (2). These structures illustrate the uncommon phenomenon of
      tautomeric polymorphism. TCB exists as two tautomers A and B. Form I (Z'=2) is
      composed of two molecules of tautomer A while Form II (Z'=1) contains a 1:1
      mixture of A and B. The polymorphs are also characterized by using other solid
      state techniques (differential scanning calorimetry (DSC), thermal gravimetric
      analysis (TGA), PXRD, FT-IR, and NMR spectroscopy). Form I is the higher melting
      form (m.p.: 177  degrees C, DeltaH(f) =~105+/-4 J g(-1)) and is the more stable
      form at room temperature. Form II is the lower melting polymorph (m.p.:  166 
      degrees C, DeltaH(f) =~86+/-3 J g(-1)) and shows high kinetic stability on
      storage in comparison to the amorphous form but it transforms readily into Form I
      in a solution-mediated process. Crystal structure analysis of co-crystals 3-11
      further confirms the existence of tautomeric polymorphism in TCB. In 3 and 11,
      tautomer A is present whereas in 4-10 the TCB molecule exists wholly as tautomer
      B. The DFT calculations suggest that the optimized tautomers A and B have nearly
      the same energies. Single point energy calculations reveal that tautomer A (in
      Form I) exists in two low-energy conformations, whereas in Form II both tautomers
      A and B exist in an unfavorable high-energy conformation, stabilized by a five
      point dimer synthon. The structural and thermodynamic features of 1-11 are
      discussed in detail. Triclabendazole is an intriguing case in which tautomeric
      and conformational variations co-exist in the polymorphs.

PMID- 22147669
TI  - Differential nanofiller cluster formations in dental adhesive systems.
AB  - Nanofillers are added to dental adhesives to improve mechanical properties of the
      hybrid layer. Ethanol or water added to the demineralized dentin to improve
      adhesive infiltration may produce filler aggregation. OBJECTIVE: To assess the
      effect of 5 vol% water or ethanol addition on nanoparticles distribution in
      dental adhesives. METHODS: Six available commercial adhesives systems were
      selected: Clearfil SE Bond (CSE), Clearfil Protect Bond (CPB), FL-Bond (FLB),
      Clearfil S3 (CS3), Bond Force (BF), One Up Bond F plus (OUB), and an experimental
      adhesive system without filler (EXP). Polymer films were obtained by adding 0
      (control) or 5 vol% water or ethanol into the bonding resins. Preparations were
      light-cured (40 s). Three specimens were analyzed for each mixture. Three phases
      and 3D images were taken from each specimen by means of an atomic force
      microscope in taping mode (TM/AFM). Cluster sizes and surface nanoroughness were
      assessed. RESULTS: Control specimens from CSE, FLB, OUB, and BF presented
      clusters. The addition of solvents lead to particles aggregation in tested
      bonding resins. Ethanol addition produced more aggregates, particularly in
      adhesives containing fluoraluminosilicate as fillers. CONCLUSIONS: Nanofillers
      aggregation occurred in all adhesive systems in presence of additional solvents.
      In general, aggregate sizes were higher after the addition of ethanol. Formed
      clusters size values are always above the dimensions of the spaces existing
      between the demineralized collagen fibers.

PMID- 22147670
TI  - Synergetic effect of host-guest chemistry and spin crossover in 3D Hofmann-like
      metal-organic frameworks [Fe(bpac)M(CN)4] (M=Pt, Pd, Ni).
AB  - The synthesis and characterization of a series of three-dimensional (3D) Hofmann
      like clathrate porous metal-organic framework (MOF) materials [Fe(bpac)M(CN)(4)]
      (M=Pt, Pd, and Ni; bpac=bis(4-pyridyl)acetylene) that exhibit spin-crossover
      behavior is reported. The rigid bpac ligand is longer than the previously used
      azopyridine and pyrazine and has been selected with the aim to improve both the
      spin-crossover properties and the porosity of the corresponding porous
      coordination polymers (PCPs). The 3D network is composed of successive
      {Fe[M(CN)(4)]}(n) planar layers bridged by the bis-monodentate bpac ligand linked
      in the apical positions of the iron center. The large void between the layers,
      which represents 41.7% of the unit cell, can accommodate solvent molecules or
      free bpac ligand. Different synthetic strategies were used to obtain a range of
      spin-crossover behaviors with hysteresis loops around room temperature; the
      samples were characterized by magnetic susceptibility, calorimetric, Mossbauer,
      and Raman measurements. The complete physical study reveals a clear relationship
      between the quantity of included bpac molecules and the completeness of the spin
      transition, thereby underlining the key role of the pi-pi stacking interactions
      operating between the host and guest bpac molecules within the network. Although
      the inclusion of the bpac molecules tends to increase the amount of active iron
      centers, no variation of the transition temperature was measured. We have also
      investigated the ability of the network to accommodate the inclusion of molecules
      other than water and bpac and studied the synergy between the host-guest
      interaction and the spin-crossover behavior. In fact, the clathration of various
      aromatic molecules revealed specific modifications of the transition temperature.
      Finally, the transition temperature and the completeness of the transition are
      related to the nature of the metal associated with the iron center (Ni, Pt, or
      Pd) and also to the nature and the amount of guest molecules in the lattice.

PMID- 22147671
TI  - Microcurrent therapy in the management of chronic tennis elbow: pilot studies to
      optimize parameters.
AB  - BACKGROUND AND PURPOSE: In microcurrent therapy (MCT), low-intensity electric
      current is applied to promote tissue healing and relieve symptoms. MCT is used
      with recalcitrant skin and bone lesions, but little is known about its effects on
      tendinopathy, and optimal treatment parameters are uncertain. Two studies were
      conducted to ascertain whether varying (i) current intensity and (ii) waveform
      and treatment duration affect outcomes of MCT for chronic tennis elbow. METHODS:
      Two trials compared the effects of different MCT parameters on pain and function,
      grip strength, and sonographically graded tendon structure and hyperaemia. Trial
      1 compared monophasic MCT of intensity 50 and 500 MUA applied for 35 h; trial 2
      compared devices delivering approximately 25 MUA but with different waveforms and
      durations of 15 and 189 h, respectively. Treatment was applied over 3 weeks.
      Assessments were at baseline and 3, 6 and 15 weeks. RESULTS: For each trial, n =
      31. In trial 1, 50 MUA was more effective than 500 MUA, with 93% of participants
      'much better' or 'fully recovered' at 15 weeks, compared with 47% in the 500 MUA
      group. Tendon structural normalization was superior at 50 MUA, but no significant
      differences were found in other outcomes. In trial 2, success rates for the two
      groups at 15 weeks were 75% and 73%, respectively, but group improvements did not
      differ significantly on any measure. Pooled analysis of data from both trials
      showed that, immediately following treatment, blood flow had fallen in the
      subgroup with high baseline scores and risen in the subgroup with low scores. Low
      baseline score correlated significantly with treatment success. CONCLUSION:
      Monophasic MCT of peak current intensity 50 MUA applied for tens of hours may be
      effective in reducing symptoms and promoting tendon normalization in chronic
      tennis elbow. Hyperaemia may help predict treatment outcome. A full-scale trial
      of the therapy is warranted.

PMID- 22147672
TI  - 2011 ACCF/AHA focused update of the guidelines for the management of patients
      with Unstable Angina/Non-ST-Elevation Myocardial Infarction (updating the 2007
      Guideline): highlights for the clinician.
AB  - The 2011 Update to the Unstable Angina/Non-ST-Elevation Myocardial Infarction
      (UA/NSTEMI) Guideline is based in evolving data or expert opinion and
      incorporates information from late-breaking clinical trials presented at the 2008
      2009 Scientific Sessions of the American College of Cardiology, the American
      Heart Association, and the European Society of Cardiology, among others, as well
      as selected data through April 2010. The 5 key issues highlighted in this summary
      are: (1) the timing of acute interventional therapy in non-ST-elevation
      myocardial infarction; (2) emphasis on the timing, duration, and application of
      dual and triple antiplatelet therapy; (3) specific recommendations for patients
      with diabetes mellitus; (4) the role and potential benefit of invasive therapy in
      patients with advanced renal dysfunction; and (5) issues of quality improvement
      for acute coronary syndromes.

PMID- 22147674
TI  - Pediatric oncology research in low income countries: ethical concepts and
      challenges.
AB  - Uneven strides in research and care have led to discrepancies in childhood cancer
      outcomes between high and low income countries (LICs). Collaborative research may
      help improve outcomes in LICs by generating knowledge for local scientific
      communities, augmenting knowledge translation, and fostering context-specific
      evaluation of treatment protocols. However, the risks of such research have
      received little attention. This paper investigates the relationship between
      pediatric oncology research in LICs and four core issues in the ethics
      literature: standard of care, trial benefits, ethics review, and informed
      consent. Our aims are to highlight the importance of this field and the need for
      further inquiry.

PMID- 22147675
TI  - Membrane composition of jetted lipid vesicles: a Raman spectroscopy study.
AB  - Microfluidic jetting is a promising method to produce giant unilamellar
      phospholipid vesicles for mimicking living cells in biomedical studies. We have
      investigated the chemical composition of membranes of vesicles prepared using
      this approach by means of Raman scattering spectroscopy. The membranes of all
      jetted vesicles are found to contain residuals of the organic solvent decane used
      in the preparation of the initial planar membrane. The decane inclusions are
      randomly distributed over the vesicle surface area and vary in thickness from a
      few to several tens of nanometers. Our findings point out that the membrane
      properties of jetted vesicles may differ considerably from those of vesicles
      prepared by other methods and from those of living cells.

PMID- 22147673
TI  - Next generation analytic tools for large scale genetic epidemiology studies of
      complex diseases.
AB  - Over the past several years, genome-wide association studies (GWAS) have
      succeeded in identifying hundreds of genetic markers associated with common
      diseases. However, most of these markers confer relatively small increments of
      risk and explain only a small proportion of familial clustering. To identify
      obstacles to future progress in genetic epidemiology research and provide
      recommendations to NIH for overcoming these barriers, the National Cancer
      Institute sponsored a workshop entitled "Next Generation Analytic Tools for Large
      Scale Genetic Epidemiology Studies of Complex Diseases" on September 15-16, 2010.
      The goal of the workshop was to facilitate discussions on (1) statistical
      strategies and methods to efficiently identify genetic and environmental factors
      contributing to the risk of complex disease; and (2) how to develop, apply, and
      evaluate these strategies for the design, analysis, and interpretation of large
      scale complex disease association studies in order to guide NIH in setting the
      future agenda in this area of research. The workshop was organized as a series of
      short presentations covering scientific (gene-gene and gene-environment
      interaction, complex phenotypes, and rare variants and next generation
      sequencing) and methodological (simulation modeling and computational resources
      and data management) topic areas. Specific needs to advance the field were
      identified during each session and are summarized.

PMID- 22147676
TI  - Depth profiling of gold nanoparticles and characterization of point spread
      functions in reconstructed and human skin using multiphoton microscopy.
AB  - Multiphoton microscopy has become popular in studying dermal nanoparticle
      penetration. This necessitates studying the imaging parameters of multiphoton
      microscopy in skin as an imaging medium, in terms of achievable detection depths
      and the resolution limit. This would simulate real-case scenarios rather than
      depending on theoretical values determined under ideal conditions. This study has
      focused on depth profiling of sub-resolution gold nanoparticles (AuNP) in
      reconstructed (fixed and unfixed) and human skin using multiphoton microscopy.
      Point spread functions (PSF) were determined for the used water-immersion
      objective of 63*/NA = 1.2. Factors such as skin-tissue compactness and the
      presence of wrinkles were found to deteriorate the accuracy of depth profiling. A
      broad range of AuNP detectable depths (20-100 MUm) in reconstructed skin was
      observed. AuNP could only be detected up to ~14 MUm depth in human skin. Lateral
      (0.5 +/- 0.1 MUm) and axial (1.0 +/- 0.3 MUm) PSF in reconstructed and human
      specimens were determined. Skin cells and intercellular components didn't degrade
      the PSF with depth. In summary, the imaging parameters of multiphoton microscopy
      in skin and practical limitations encountered in tracking nanoparticle
      penetration using this approach were investigated.

PMID- 22147677
TI  - The potential role of nutritional genomics tools in validating high health foods
      for cancer control: broccoli as example.
AB  - Nutritional genomics reflects gene/nutrient interactions, utilising high
      throughput genomic tools in nutrition research. The field also considers the
      contribution of individual genotypes to wellness and the risk of chronic disease
      (nutrigenetics), and how such genetic predisposition may be modified by
      appropriate diets. For example, high consumption of brassicaceous vegetables,
      including broccoli, has regularly associated with low cancer risk. Bioactive
      chemicals in broccoli include glucosinolates, plant pigments including
      kaempferol, quercetin, lutein and carotenoids, various vitamins, minerals and
      amino acids. Cancer prevention is hypothesised to act through various mechanisms
      including modulation of xenobiotic metabolising enzymes, NF-E2 p45-related factor
      2 (Nrf2)-mediated stress-response mechanisms, and protection against genomic
      instability. Broccoli and broccoli extracts also regulate the progression of
      cancer through anti-inflammatory effects, effects on signal transduction,
      epigenetic effects and modulation of the colonic microflora. Human intervention
      studies with broccoli and related foods, using standard biomarker methodologies,
      reveal part of a complex picture. Nutrigenomic approaches, especially
      transcriptomics, enable simultaneous study of various signalling pathways and
      networks. Phenotypic, genetic and/or metabolic stratification may identify
      individuals most likely to respond positively to foods or diets. Jointly, these
      technologies can provide proof of human efficacy, and may be essential to ensure
      effective market transfer and uptake of broccoli and related foods.

PMID- 22147678
TI  - Aurophilicity versus mercurophilicity: impact of d10-d10 metallophilic
      interactions on the structure of metal-rich supramolecular assemblies.
AB  - Treatment of U-shaped, binuclear Cu(I) complexes 1,1' (1, counterion: BF(4)(-);
      1', counterion: PF(6)(-)) with metal cyanide linear linkers K[Au(CN)(2)] (3) and
      Hg(CN)(2) (4) lead to formation of new supramolecular assemblies 5,5' and 6,6',
      respectively, in good yield. These derivatives have been characterized by NMR
      spectroscopy, IR, and X-ray diffraction studies. Derivative 5,5' are
      supramolecular metallacycles in which intramolecular aurophilic interactions
      between the Au(I) metal centers of the linkers are observed. Derivative 5
      crystallizes as a single solid phase, whereas derivative 5' is characterized in
      the solid state as four different pseudo-polymorphs (5'a-d). Notably in the case
      of phase 5'd, a dimer of supramolecular metallacycles bounded by intermolecular
      aurophilic interactions is formed. Conversely, derivatives 6,6' present large
      structural diversity depending on the nature of the counterion. Derivative 6 is a
      supramolecular rectangle in which the Hg(II)-Hg(II) metal distance suggests
      mercurophilic interaction, whereas 6' crystallizes as two different pseudo
      polymorphs 6'a,b, that is, a one-dimensional coordination polymer and one
      oligomer with no short Hg(II)-Hg(II) metal contacts, respectively. In derivatives
      6,6', short contacts between the Hg(II) metal centers and fluorine atoms of the
      counterions are also observed, which may explain the counterion structural
      dependence of these supramolecular assemblies based on Hg(II) metal cyanide
      linker. Comparison of the different solid-state structures characterized
      highlights the importance of weak secondary interactions between the linkers for
      the formation supramolecular metallacycles from molecular clips 1,1' and suggests
      the range of energies required for these interactions to form metallacycles and
      to induce self-aggregation.

PMID- 22147679
TI  - Back-scattered electron imaging for leakage analysis of four retrofilling
      materials.
AB  - This study aimed to evaluate, ex vivo, the nanoleakage in dentinal tubules, the
      linear infiltration of silver nitrate in the dentin wall/root-end filling
      material interface, and the presence of gaps in this interface in root-end
      cavities filled with 4 filling materials. Forty-eight disto-buccal root canals of
      maxillary molars were instrumented and filled. Retrograde cavities were prepared
      with ultrasonic points (apical 2 mm). The samples were divided into 2 control
      groups (n = 4) and 4 experimental groups (n = 10): Group I--white mineral
      trioxide aggregate (MTA); Group II--Super EBA; Group III--Portland cement; and
      Group IV--Sealer 26. After 1 week, the specimens were subjected to silver nitrate
      and prepared for SEM (backscattered electrons). In the apical-apical segment, an
      area with significantly higher leakage was observed for Super EBA, followed by
      Portland cement, MTA, and Sealer 26 (P = 0.0054). In the medium and cervical
      segments, all materials showed the same leakage behavior (P = 0.1815 and P =
      0.1723, respectively). The linear infiltration at the dentin wall/root-end
      filling material interface was higher with Super EBA than the other groups. No
      differences in the percentage of gaps along the 3 mm of dentin wall/root-end
      filling material interface between the 4 materials were evident (P > 0.05).
      Nanoleakage occurred mainly in the apical segment of the samples, and Super EBA
      showed the highest values. The area and linear leakage were lower in the middle
      and coronal segments, regardless of the root-end filling material. No material
      perfectly sealed the root-end cavities, which allowed for the leakage occurrence.

PMID- 22147680
TI  - Comparison of two resistance training protocols, 6RM versus 12RM, to increase the
      1RM in healthy young adults. A single-blind, randomized controlled trial.
AB  - PURPOSE: The purpose of the study is to compare the effect in healthy young
      adults of two resistance training protocols, six-repetition maximum (RM) versus
      12RM on maximum strength (1RM). METHOD: A single-blind, randomized controlled
      trial was used in the study. Sixty-two healthy physical therapy students, with
      age (mean [+standard deviation]) 23 (+2.6)  years, weight 67.4 (+11.7)  kg and
      height 171.7 (+8.4)  cm, of both genders who were recreationally active, but not
      training systematically, volunteered to participate in the study. They were
      randomized into two groups (group 1: 24 women and 8 men; group 2: 23 women and 7
      men) by a block randomization procedure that ensured equal gender distribution.
      Sealed envelopes were used to conceal allocation to groups. INTERVENTIONS: Group
      1 did three sets of 6RM of each exercise, and group 2 did three sets of 12RM.
      Both groups performed the exercises twice per week for 8 weeks with 3 minutes
      rest between sets and exercises. Primary outcomes were maximum strength defined
      as one-repetition maximum squat (1RMSq) for lower-body strength and bench press
      (1RMBp) for upper-body strength. Secondary outcomes were body weight and Uro
      Kaleva Kekkonen (UKK) Fitness Index. RESULTS: Both groups increased strength
      significantly (p < 0.001) in 1RMSq (6RM 13.6%, 12RM 13.5%) and 1RMBp (6RM 9.2%,
      12RM 8.4%). There was no significant difference in the change between the two
      groups, no change in body weight and only a small increase in UKK Fitness Index.
      CONCLUSION: Both 6RM and 12RM training protocols improve maximum strength in
      recreationally active healthy young adults, with no significant difference
      between the protocols.

PMID- 22147681
TI  - Intraaortic balloon pump: incidence and predictors of complications in the
      Florence registry.
AB  - BACKGROUND: The intraaortic balloon pump (IABP) is the most commonly used
      mechanical circulatory support for patients with acute coronary syndromes and
      cardiogenic shock. Nevertheless, IABP-related complications are still frequent
      and associated with a poor prognosis. HYPOTHESIS: To prospectively assess the
      incidence and predictors of complications in patients treated with IABP. METHODS:
      A total of 481 patients treated with IABP were prospectively enrolled in our
      registry (the Florence Registry). At multivariable logistic regression analysis
      the following variables were independent predictors for complications (when
      adjusted for age >75 years, eGFR and time length of IABP support): use of
      inotropes (OR 2.450, P < 0.017), nadir platelet count (1000/uL step; OR 0.990, P
      < 0.001), admission lactate (OR 1.175, P = 0.003). Nadir platelet count showed a
      negative correlation with length of time of IABP implantation (r-0.31; P <
      0.001). A nadir platelet count cutoff value of less than 120,000 was identified
      using a receiver operating characteristic (ROC) curve for the development of
      complications (area under the curve [AUC] 0.70; P < 0.001). RESULTS:
      Complications were observed in the 13.1%, among whom 33 of 63 showed major
      bleeding. The incidence of complications was higher in patients aged >75 years (P
      = 0.015) and in those who had an IABP implanted for more than 24 hours (P =
      0.001). Patients with complications showed an in Intensive Cardiac Care Unit
      (ICCU) mortality higher than patients who did not (44.4% vs 17.2%, P < 0.001).
      CONCLUSIONS: In consecutive patients treated with IABP support, the degree of
      hemodynamic impairment and the decrease in platelet count were independent
      predictors of complications, whose development was associated with higher in-ICCU
      mortality.

PMID- 22147682
TI  - Patients with idiopathic rapid-eye-movement sleep behavior disorder show normal
      gastric motility assessed by the 13C-octanoate breath test.
AB  - BACKGROUND: Delayed gastric emptying is a non-motor symptom of Parkinson's
      disease. Few data exist on gastric emptying in early-stage Parkinson's disease.
      In idiopathic rapid-eye-movement sleep behavior disorder, a presumable pre-motor
      stage of Parkinson's disease, gastric emptying has not yet been investigated.
      METHODS: Twenty healthy controls, 13 patients with idiopathic rapid-eye-movement
      sleep behavior disorder, and 39 patients with Parkinson's disease patients
      underwent standardized testing for gastric emptying with the (13)C-octanoate
      breath test. RESULTS: Gastric emptying was significantly delayed in drug-naive (P
      < .001) and in treated Parkinson's disease patients (P < .001), but normal in
      patients with idiopathic rapid-eye-movement sleep behavior disorder. CONCLUSIONS:
      Our study confirms delayed gastric emptying in drug-naive, early-stage
      Parkinson's disease. Normal gastric emptying in idiopathic rapid-eye-movement
      sleep behavior disorder might be explained by the fact that neurodegenerative
      changes in structures modulating gastric motility are not severe enough to cause
      a functional deficit that can be detected by the (13)C-octanoate breath test.

PMID- 22147683
TI  - Improved Li-storage performance of Li4Ti5O12 coated with C-N compounds derived
      from pyrolysis of urea through a low-temperature approach.
AB  - A uniform and thin amorphous layer of a C-N compound was coated on porous
      Li(4)Ti(5)O(12) by pyrolysis of urea on its surface at a rather low temperature
      of 400  degrees C in an Ar atmosphere. Such a C-N coating layer greatly improved
      the electrochemical performance of Li(4)Ti(5)O(12). After coating,
      Li(4)Ti(5)O(12) showed good rate and excellent cycling performance. Reversible
      capacities for the coated sample of 134 and 105 mAh g(-1) were obtained at
      current rates of 5C and 10C, respectively, in the voltage range of 1-2.2 V, which
      is approximately two and five times higher than those of pristine Li(4)Ti(5)O(12)
      at the same current rates. Excellent capacity retention of 95.8 % was achieved
      for the coated sample after 2000 cycles in a half cell at a 2C rate.

PMID- 22147684
TI  - Sun-believable solar paint. A transformative one-step approach for designing
      nanocrystalline solar cells.
AB  - A transformative approach is required to meet the demand of economically viable
      solar cell technology. By making use of recent advances in semiconductor
      nanocrystal research, we have now developed a one-coat solar paint for designing
      quantum dot solar cells. A binder-free paste consisting of CdS, CdSe, and TiO(2)
      semiconductor nanoparticles was prepared and applied to conducting glass surface
      and annealed at 473 K. The photoconversion behavior of these semiconductor film
      electrodes was evaluated in a photoelectrochemical cell consisting of graphene
      Cu(2)S counter electrode and sulfide/polysulfide redox couple. Open-circuit
      voltage as high as 600 mV and short circuit current of 3.1 mA/cm(2) were obtained
      with CdS/TiO(2)-CdSe/TiO(2) electrodes. A power conversion efficiency exceeding
      1% has been obtained for solar cells constructed using the simple conventional
      paint brush approach under ambient conditions. Whereas further improvements are
      necessary to develop strategies for large area, all solid state devices, this
      initial effort to prepare solar paint offers the advantages of simple design and
      economically viable next generation solar cells.

PMID- 22147685
TI  - Guest-responsive covalent frameworks by the cross-linking of liquid-crystalline
      salts: tuning of lattice flexibility by the design of polymerizable units.
AB  - Cross-linked polymers prepared by the in-situ polymerization of liquid
      crystalline salts were found to work as solid-state hosts with a flexible
      framework. As a component of such hosts, four kinds of polymerizable amphiphilic
      carboxylic acids bearing alkyl chains with acryloyloxy (A), dienyl (D), and/or
      nonreactive (N) chain ends (monomeric carboxylic acids; M(AAA), M(ANA), M(DDD),
      and M(DND)) were used. The carboxylic acids were mixed with an equimolar amount
      of a template unit, (1R,2S)-norephedrine (guest amine; G(RS)), to form the
      corresponding salts. Every salt exhibited a rectangular columnar LC phase at room
      temperature, which was successfully polymerized by (60)Co gamma-ray-induced
      polymerization without serious structural disordering to afford the salt of cross
      linked carboxylic acid (polymeric carboxylic acid; P(AAA), P(ANA), P(DDD), and
      P(DND)) with G(RS) . Owing to the noncovalency of the interactions between the
      polymer framework P and the template G(RS), the cross-linked polymers could
      reversibly release and capture a meaningful amount of G(RS). In response to the
      desorption and adsorption of G(RS), the cross-linked polymers dramatically
      switched their nanoscale structural order. A systematic comparison of the
      polymers revealed that the choice of polymerizable groups has a significant
      influence on the properties of the resultant polymer frameworks as solid-state
      hosts. Among these polymers, P(DDD) was found to be an excellent solid-state
      host, in terms of guest-releasing/capturing ability, guest-recognition ability,
      durability to repetitive usage, and unique structural switching mode.

PMID- 22147686
TI  - Capillary electrophoresis of natural products: highlights of the last five years
      (2006-2010).
AB  - An extensive search of the published research and review articles indicated a
      growing number of works that employed electroseparation techniques. Capillary
      zone electrophoresis (CZE) and electrokinetic chromatography (EKC), in
      particular, were found to be popular for the analyses of natural products. This
      review outlines the important developments in this field over the years,
      especially during the 2006-2010 period. An overview of the natural product
      applications such as pharmaceuticals/herbal products, fingerprinting and quality
      control, food and food contaminants, and toxicological compounds of interest to
      forensics were presented. Important areas of detection strategies, microchips,
      sample preconcentration, and chiral separations were also discussed. Hence, quick
      information was provided on the researches already undertaken and the
      possibilities of unexplored areas. In addition, fundamental concepts for the
      understanding of CZE and EKC and their suitability for natural products analyses
      were briefly discussed.

PMID- 22147687
TI  - Revelation of topological surface states in Bi2Se3 thin films by in situ Al
      passivation.
AB  - Topological insulators (TIs) are extraordinary materials that possess massless,
      Dirac-like topological surface states in which backscattering is prohibited due
      to the strong spin-orbit coupling. However, there have been reports on
      degradation of topological surface states in ambient conditions, which presents a
      great challenge for probing the original topological surface states after TI
      materials are prepared. Here, we show that in situ Al passivation inside a
      molecular beam epitaxy (MBE) chamber could inhibit the degradation process and
      reveal the pristine topological surface states. Dual evidence from Shubnikov-de
      Hass (SdH) oscillations and weak antilocalization (WAL) effect, originated from
      the pi Berry phase, suggests that the helically spin-polarized surface states are
      well preserved by the proposed in situ Al passivation. In contrast, we show the
      degradation of surface states for the unpassivated control samples, in which the
      2D carrier density is increased 39.2% due to ambient n-doping, the SdH
      oscillations are completely absent, and a large deviation from WAL is observed.

PMID- 22147688
TI  - Single molecule fluorescence under conditions of fast flow.
AB  - We have experimentally determined the optimal flow velocities to characterize or
      count single molecules by using a simple microfluidic device to perform two-color
      coincidence detection (TCCD) and single pair Forster resonance energy transfer
      (spFRET) using confocal fluorescence spectroscopy on molecules traveling at
      speeds of up to 10 cm s(-1). We show that flowing single fluorophores at >=0.5 cm
      s(-1) reduces the photophysical processes competing with fluorescence, enabling
      the use of high excitation irradiances to partially compensate for the short
      residence time within the confocal volume (10-200 MUs). Under these conditions,
      the data acquisition rate can be increased by a maximum of 38-fold using TCCD at
      5 cm s(-1) or 18-fold using spFRET at 2 cm s(-1), when compared with diffusion.
      While structural characterization requires more photons to be collected per event
      and so necessitates the use of slower speeds (2 cm s(-1) for TCCD and 1 cm s(-1)
      for spFRET), a considerable enhancement in the event rate could still be obtained
      (33-fold for TCCD and 16-fold for spFRET). Using flow under optimized conditions,
      analytes could be rapidly quantified over a dynamic range of up to 4 orders of
      magnitude by direct molecule counting; a 50 fM dual-labeled model sample can be
      detected with 99.5% statistical confidence in around 8 s using TCCD and a flow
      velocity of 5 cm s(-1).

PMID- 22147689
TI  - Environmental mass spectrometry: emerging contaminants and current issues.

PMID- 22147690
TI  - Plasma half-life extension of small recombinant antibodies by fusion to
      immunoglobulin-binding domains.
AB  - Many therapeutic proteins possessing a small size are rapidly cleared from
      circulation. Half-life extension strategies have therefore become increasingly
      important to improve the pharmacokinetic and pharmacodynamic properties of
      protein therapeutics. Here, we performed a comparative analysis of the half-life
      extension properties of various bacterial immunoglobulin-binding domains (IgBDs)
      derived from Staphylococcus protein A (SpA), Streptococcus protein G (SpG), and
      Finegoldia (formerly Peptostreptococcus) protein L (PpL). These domains, composed
      of 50-60 amino acid residues, were fused to the C terminus of a single-chain Fv
      and a bispecific single-chain diabody, respectively. All fusion proteins were
      produced in mammalian cells and retained their antigen-binding properties. The
      half-lives of the antibody molecules were prolonged to varying extents for the
      different IgBDs. The strongest effects in mice were observed for domain C3 of SpG
      (SpG(C3)) followed by domains B and D of SpA, suggesting that SpG(C3) is
      particularly useful to extend the plasma half-life of small proteins.

PMID- 22147691
TI  - Charge-based interaction conserved within histone H3 lysine 4 (H3K4)
      methyltransferase complexes is needed for protein stability, histone methylation,
      and gene expression.
AB  - Histone H3 lysine 4 (H3K4) methyltransferases are conserved from yeast to humans,
      assemble in multisubunit complexes, and are needed to regulate gene expression.
      The yeast H3K4 methyltransferase complex, Set1 complex or complex of proteins
      associated with Set1 (COMPASS), consists of Set1 and conserved Set1-associated
      proteins: Swd1, Swd2, Swd3, Spp1, Bre2, Sdc1, and Shg1. The removal of the WD40
      domain-containing subunits Swd1 and Swd3 leads to a loss of Set1 protein and
      consequently a complete loss of H3K4 methylation. However, until now, how these
      WD40 domain-containing proteins interact with Set1 and contribute to the
      stability of Set1 and H3K4 methylation has not been determined. In this study, we
      identified small basic and acidic patches that mediate protein interactions
      between the C terminus of Swd1 and the nSET domain of Set1. Absence of either the
      basic or acidic patches of Set1 and Swd1, respectively, disrupts the interaction
      between Set1 and Swd1, diminishes Set1 protein levels, and abolishes H3K4
      methylation. Moreover, these basic and acidic patches are also important for cell
      growth, telomere silencing, and gene expression. We also show that the basic and
      acidic patches of Set1 and Swd1 are conserved in their human counterparts SET1A/B
      and RBBP5, respectively, and are needed for the protein interaction between SET1A
      and RBBP5. Therefore, this charge-based interaction is likely important for
      maintaining the protein stability of the human SET1A/B methyltransferase
      complexes so that proper H3K4 methylation, cell growth, and gene expression can
      also occur in mammals.

PMID- 22147692
TI  - C5a-regulated CCAAT/enhancer-binding proteins beta and delta are essential in
      Fcgamma receptor-mediated inflammatory cytokine and chemokine production in
      macrophages.
AB  - CCAAT/enhancer-binding protein beta (C/EBPbeta) and C/EBPdelta are known to
      participate in the regulation of many genes associated with inflammation.
      However, little is known about the activation and function of C/EBPbeta and 
      delta in inflammatory responses elicited by Fcgamma receptor (FcgammaR)
      activation. Here we show that C/EBPbeta and -delta activation are induced in IgG
      immune complex (IC)-treated macrophages. The increased expression of C/EBPbeta
      and -delta occurred at both mRNA and protein levels. Furthermore, induction of
      C/EBPbeta and -delta was mediated, to a large extent, by activating FcgammaRs.
      Using siRNA-mediated knockdown as well as macrophages deficient for C/EBPbeta
      and/or -delta, we demonstrate that C/EBPbeta and -delta play a critical role in
      the production of TNF-alpha, MIP-2, and MIP-1alpha in IgG IC-stimulated
      macrophages. Moreover, both ERK1/2 and p38 MAPK are involved in C/EBP induction
      and TNF-alpha, MIP-2, and MIP-1alpha production induced by IgG IC. We provide the
      evidence that C5a regulates IgG IC-induced inflammatory responses by enhancing
      ERK1/2 and p38 MAPK activities as well as C/EBPbeta and -delta activities.
      Collectively, these data suggest that C/EBPbeta and -delta are key regulators for
      FcgammaR-mediated induction of cytokines and chemokines in macrophages.
      Furthermore, C/EBPs may play an important regulatory role in IC-associated
      inflammatory responses.

PMID- 22147693
TI  - Computational investigation of glycosylation effects on a family 1 carbohydrate
      binding module.
AB  - Carbohydrate-binding modules (CBMs) are ubiquitous components of glycoside
      hydrolases, which degrade polysaccharides in nature. CBMs target specific
      polysaccharides, and CBM binding affinity to cellulose is known to be
      proportional to cellulase activity, such that increasing binding affinity is an
      important component of performance improvement. To ascertain the impact of
      protein and glycan engineering on CBM binding, we use molecular simulation to
      quantify cellulose binding of a natively glycosylated Family 1 CBM. To validate
      our approach, we first examine aromatic-carbohydrate interactions on binding, and
      our predictions are consistent with previous experiments, showing that a tyrosine
      to tryptophan mutation yields a 2-fold improvement in binding affinity. We then
      demonstrate that enhanced binding of 3-6-fold over a nonglycosylated CBM is
      achieved by the addition of a single, native mannose or a mannose dimer,
      respectively, which has not been considered previously. Furthermore, we show that
      the addition of a single, artificial glycan on the anterior of the CBM, with the
      native, posterior glycans also present, can have a dramatic impact on binding
      affinity in our model, increasing it up to 140-fold relative to the
      nonglycosylated CBM. These results suggest new directions in protein engineering,
      in that modifying glycosylation patterns via heterologous expression,
      manipulation of culture conditions, or introduction of artificial glycosylation
      sites, can alter CBM binding affinity to carbohydrates and may thus be a general
      strategy to enhance cellulase performance. Our results also suggest that CBM
      binding studies should consider the effects of glycosylation on binding and
      function.

PMID- 22147694
TI  - Chaperoning of mutant p53 protein by wild-type p53 protein causes hypoxic tumor
      regression.
AB  - Mutant (Mt) p53 abrogates tumor suppression functions of wild-type (WT) p53
      through mutant-specific, gain-of-function effects, and patients bearing Mt p53
      are chemoresistant. The dominant negative effect of p53 mutants results from
      their aggregation propensity which causes co-aggregation of WT p53. We explored
      the mechanism of p53 inactivation in hypoxia and hypothesized whether WT p53
      could rescue Mt p53 in hypoxic tumors. WT p53 exists in mutant conformation in
      hypoxic core of MCF-7 solid tumors, and its conformation is oxygen-dependent.
      Under simulated hypoxia in cells, WT p53 undergoes conformational change in
      acquiring mutant conformation. An in vivo chaperone assay shows that WT p53
      functions as a molecular chaperone in rescuing conformational and structural p53
      mutants in cancer cells both at the transcription and proteome levels. WT p53
      chaperone therapy is further shown to cause significant regression of tumor
      xenografts through reconversion of the mutant phenotype to wild-type p53. The
      chaperone function of WT p53 is directly linked to the induction of apoptosis in
      both cancer cells and tumor xenografts. As oncogenic p53 mutants are linked to
      chemoresistance in hypoxic tumors, p53 chaperone therapy will introduce new
      dimensions to existing cancer therapeutics. We propose that in cancer cells, WT
      p53 chaperoning may either exist as a cellular event to potentially reverse the
      dominant negative effect of its oncogenic mutants or to stabilize yet
      unidentified factors.

PMID- 22147695
TI  - Redox outside the box: linking extracellular redox remodeling with intracellular
      redox metabolism.
AB  - Aerobic organisms generate reactive oxygen species as metabolic side products and
      must achieve a delicate balance between using them for signaling cellular
      functions and protecting against collateral damage. Small molecule (e.g.
      glutathione and cysteine)- and protein (e.g. thioredoxin)-based buffers regulate
      the ambient redox potentials in the various intracellular compartments, influence
      the status of redox-sensitive macromolecules, and protect against oxidative
      stress. Less well appreciated is the fact that the redox potential of the
      extracellular compartment is also carefully regulated and is dynamic. Changes in
      intracellular metabolism alter the redox poise in the extracellular compartment,
      and these are correlated with cellular processes such as proliferation,
      differentiation, and death. In this minireview, the mechanism of extracellular
      redox remodeling due to intracellular sulfur metabolism is discussed in the
      context of various cell-cell communication paradigms.

PMID- 22147696
TI  - Biochemical analysis of matrix metalloproteinase activation of chemokines CCL15
      and CCL23 and increased glycosaminoglycan binding of CCL16.
AB  - Leukocyte migration and activation is orchestrated by chemokines, the cleavage of
      which modulates their activity and glycosaminoglycan binding and thus their roles
      in inflammation and immunity. Early research identified proteolysis as a means of
      both activating or inactivating CXC chemokines and inactivating CC chemokines.
      Recent evidence has shown activating cleavages of the monocyte chemoattractants
      CCL15 and CCL23 by incubation with synovial fluid, although the responsible
      proteases could not be identified. Herein we show that CCL15 is processed in
      human synovial fluid by matrix metalloproteinases (MMPs) and serine proteases.
      Furthermore, a family-wide investigation of MMP processing of all 14 monocyte
      directed CC chemokines revealed that each is precisely cleaved by one or more
      MMPs. By MALDI-TOF-MS, 149 cleavage sites were sequenced including the first
      reported instance of CCL1, CCL16, and CCL17 proteolysis. Full-length CCL15-(1-92)
      and CCL23-(1-99) were cleaved within their unique 31 and 32-amino acid residue
      extended amino termini, respectively. Unlike other CCL chemokines that lose
      activity and become receptor antagonists upon MMP cleavage, the prominent MMP
      processed products CCL15-(25-92, 28-92) and CCL23-(26-99) are stronger agonists
      in calcium flux and Transwell CC receptor transfectant and monocytic THP-1
      migration assays. MMP processing of CCL16-(1-97) in its extended carboxyl
      terminus yields two products, CCL16-(8-77) and CCL16-(8-85), with both showing
      unexpected enhanced glycosaminoglycan binding. Hence, our study reveals for the
      first time that MMPs activate the long amino-terminal chemokines CCL15 and CCL23
      to potent forms that have potential to increase monocyte recruitment during
      inflammation.

PMID- 22147697
TI  - Different 8-hydroxyquinolines protect models of TDP-43 protein, alpha-synuclein,
      and polyglutamine proteotoxicity through distinct mechanisms.
AB  - No current therapies target the underlying cellular pathologies of age-related
      neurodegenerative diseases. Model organisms provide a platform for discovering
      compounds that protect against the toxic, misfolded proteins that initiate these
      diseases. One such protein, TDP-43, is implicated in multiple neurodegenerative
      diseases, including amyotrophic lateral sclerosis and frontotemporal lobar
      degeneration. In yeast, TDP-43 expression is toxic, and genetic modifiers first
      discovered in yeast have proven to modulate TDP-43 toxicity in both neurons and
      humans. Here, we describe a phenotypic screen for small molecules that reverse
      TDP-43 toxicity in yeast. One group of hit compounds was 8-hydroxyquinolines (8
      OHQ), a class of clinically relevant bioactive metal chelators related to
      clioquinol. Surprisingly, in otherwise wild-type yeast cells, different 8-OHQs
      had selectivity for rescuing the distinct toxicities caused by the expression of
      TDP-43, alpha-synuclein, or polyglutamine proteins. In fact, each 8-OHQ
      synergized with the other, clearly establishing that they function in different
      ways. Comparative growth and molecular analyses also revealed that 8-OHQs have
      distinct metal chelation and ionophore activities. The diverse bioactivity of 8
      OHQs indicates that altering different aspects of metal homeostasis and/or
      metalloprotein activity elicits distinct protective mechanisms against several
      neurotoxic proteins. Indeed, phase II clinical trials of an 8-OHQ has produced
      encouraging results in modifying Alzheimer disease. Our unbiased identification
      of 8-OHQs in a yeast TDP-43 toxicity model suggests that tailoring 8-OHQ activity
      to a particular neurodegenerative disease may be a viable therapeutic strategy.

PMID- 22147698
TI  - Calcium binding to leptospira outer membrane antigen LipL32 is not necessary for
      its interaction with plasma fibronectin, collagen type IV, and plasminogen.
AB  - LipL32 is the most abundant outer membrane protein from pathogenic Leptospira and
      has been shown to bind extracellular matrix (ECM) proteins as well as Ca(2+).
      Recent crystal structures have been obtained for the protein in the apo- and
      Ca(2+)-bound forms. In this work, we produced three LipL32 mutants (D163-168A,
      Q67A, and S247A) and evaluated their ability to interact with Ca(2+) and with ECM
      glycoproteins and human plasminogen. The D163-168A mutant modifies aspartate
      residues involved in Ca(2+) binding, whereas the other two modify residues in a
      cavity on the other side of the protein structure. Loss of calcium binding in the
      D163-D168A mutant was confirmed using intrinsic tryptophan fluorescence, circular
      dichroism, and thermal denaturation whereas the Q67A and S247A mutants presented
      the same Ca(2+) affinity as the wild-type protein. We then evaluated if Ca(2+)
      binding to LipL32 would be crucial for its interaction with collagen type IV and
      plasma proteins fibronectin and plasminogen. Surprisingly, the wild-type protein
      and all three mutants, including the D163-168A variant, bound to these ECM
      proteins with very similar affinities, both in the presence and absence of Ca(2+)
      ions. In conclusion, calcium binding to LipL32 may be important to stabilize the
      protein, but is not necessary to mediate interaction with host extracellular
      matrix proteins.

PMID- 22147699
TI  - Thematic minireview series on redox sensing and regulation.

PMID- 22147700
TI  - Macromolecular crowding regulates assembly of mRNA stress granules after osmotic
      stress: new role for compatible osmolytes.
AB  - The massive uptake of compatible osmolytes such as betaine, taurine, and myo
      inositol is a protective response shared by all eukaryotes exposed to hypertonic
      stress. Their accumulation results mostly from the expression of specific
      transporters triggered by the transcriptional factor NFAT5/TonEBP. This allows
      the recovery of the cell volume without increasing intracellular ionic strength.
      In this study we consider the assembly and dissociation of mRNA stress granules
      (SGs) in hypertonic-stressed cells and the role of compatible osmolytes. In
      agreement with in vitro results obtained on isolated mRNAs, both macromolecular
      crowding and a high ionic strength favor the assembly of SGs in normal rat kidney
      epithelial cells. However, after hours of constant hypertonicity, the slow
      accumulation in the cytoplasm of compatible osmolytes via specific transporters
      both reduces macromolecular crowding and ionic strength, thus leading to the
      progressive dissociation of SGs. In line with this, when cells are exposed to
      hypertonicity to accumulate a large amount of compatible osmolytes, the formation
      of SGs is severely impaired, and cells increase their chances of survival to
      another hypertonic episode. Altogether, these results indicate that the impact of
      compatible osmolytes on the mRNA-associated machineries and especially that
      associated with SGs may play an important role in cell resistance and adaption to
      hyperosmolarity in many tissues like kidney and liver.

PMID- 22147701
TI  - Regulation by S-nitrosylation of protein post-translational modification.
AB  - Protein post-translational modification by S-nitrosylation conveys a ubiquitous
      influence of nitric oxide on signal transduction in eukaryotic cells. The wide
      functional purview of S-nitrosylation reflects in part the regulation by S
      nitrosylation of the principal protein post-translational modifications that play
      a role in cell signaling, including phosphorylation, acetylation, ubiquitylation
      and related modifications, palmitoylation, and alternative Cys-based redox
      modifications. In this minireview, we discuss the mechanisms through which S
      nitrosylation exerts its broad pleiotropic influence on protein post
      translational modification.

PMID- 22147702
TI  - A novel role for alpha-tocopherol transfer protein (alpha-TTP) in protecting
      against chloroquine toxicity.
AB  - Chloroquine (CQ) is a widely prescribed anti-malarial agent and is also
      prescribed to treat autoimmune diseases. Clinical treatment with CQ is often
      accompanied by serious side effects such as hepatitis and retinopathy. As a weak
      base, CQ accumulates in intracellular acidic organelles, raises the pH, and
      induces osmotic swelling and permeabilization of acidic organelles, which account
      for CQ-induced cytotoxicity. We reported previously that CQ treatment caused
      alpha-tocopherol transfer protein (alpha-TTP), a gene product of familial vitamin
      E deficiency, to change its location from the cytosol to the surface of acidic
      organelles. Here we show that alpha-TTP plays a novel role in protecting against
      CQ toxicity both in vitro and in vivo. In the presence of CQ, rat hepatoma
      McARH7777 cells, which do not express alpha-TTP endogenously, showed more severe
      cytotoxicity, such as larger vacuolation of acidic organelles and caspase
      activation, than alpha-TTP transfectant cells. Similarly, alpha-TTP knockout mice
      showed more severe CQ toxicity, such as hepatotoxicity and retinopathy, than wild
      type mice. These effects were not ameliorated by vitamin E supplementation. In
      contrast to bafilomycin A1 treatment, which prevents CQ accumulation in cells by
      raising the pH of acidic organelles, alpha-TTP expression prevented CQ
      accumulation without affecting the pH of acidic organelles. Taken together, our
      data suggest that alpha-TTP protects against CQ toxicity by preventing CQ
      accumulation in acidic organelles through a mechanism distinct from vitamin E
      transport.

PMID- 22147703
TI  - Analysis of the mobilities of band 3 populations associated with ankyrin protein
      and junctional complexes in intact murine erythrocytes.
AB  - Current models of the erythrocyte membrane depict three populations of band 3:
      (i) a population tethered to spectrin via ankyrin, (ii) a fraction attached to
      the spectrin-actin junctional complex via adducin, and (iii) a freely diffusing
      population. Because many studies of band 3 diffusion also distinguish three
      populations of the polypeptide, it has been speculated that the three populations
      envisioned in membrane models correspond to the three fractions observed in
      diffusion analyses. To test this hypothesis, we characterized band 3 diffusion by
      single-particle tracking in wild-type and ankyrin- and adducin-deficient
      erythrocytes. We report that ~40% of total band 3 in wild-type murine
      erythrocytes is attached to ankyrin, whereas ~33% is immobilized by adducin, and
      ~27% is not attached to any cytoskeletal anchor. More detailed analyses reveal
      that mobilities of individual ankyrin- and adducin-tethered band 3 molecules are
      heterogeneous, varying by nearly 2 orders of magnitude and that there is
      considerable overlap in diffusion coefficients for adducin and ankyrin-tethered
      populations. Taken together, the data suggest that although the ankyrin- and
      adducin-immobilized band 3 can be monitored separately, significant heterogeneity
      still exists within each population, suggesting that structural and compositional
      properties likely vary considerably within each band 3 complex.

PMID- 22147704
TI  - Peroxiredoxin functions as a peroxidase and a regulator and sensor of local
      peroxides.
AB  - Peroxiredoxins (Prxs) contain an active site cysteine that is sensitive to
      oxidation by H(2)O(2). Mammalian cells express six Prx isoforms that are
      localized to various cellular compartments. The oxidized active site cysteine of
      Prx can be reduced by a cellular thiol, thus enabling Prx to function as a
      locally constrained peroxidase. Regulation of Prx via phosphorylation in response
      to extracellular signals allows the local accumulation of H(2)O(2) and thereby
      enables its messenger function. The fact that the oxidation state of the active
      site cysteine of Prx can be transferred to other proteins that are less
      intrinsically susceptible to H(2)O(2) also allows Prx to function as an H(2)O(2)
      sensor.

PMID- 22147705
TI  - An amyloid organelle, solid-state NMR evidence for cross-beta assembly of gas
      vesicles.
AB  - Functional amyloids have been identified in a wide range of organisms, taking on
      a variety of biological roles and being controlled by remarkable mechanisms of
      directed assembly. Here, we report that amyloid fibrils constitute the ribs of
      the buoyancy organelles of Anabaena flos-aquae. The walls of these gas-filled
      vesicles are known to comprise a single protein, GvpA, arranged in a low pitch
      helix. However, the tertiary and quaternary structures have been elusive. Using
      solid-state NMR correlation spectroscopy we find detailed evidence for an
      extended cross-beta structure. This amyloid assembly helps to account for the
      strength and amphiphilic properties of the vesicle wall. Buoyancy organelles thus
      dramatically extend the scope of known functional amyloids.

PMID- 22147706
TI  - Rigid core and flexible terminus: structure of solubilized light-harvesting
      chlorophyll a/b complex (LHCII) measured by EPR.
AB  - The structure of the major light-harvesting chlorophyll a/b complex (LHCII) was
      analyzed by pulsed EPR measurements and compared with the crystal structure. Site
      specific spin labeling of the recombinant protein allowed the measurement of
      distance distributions over several intra- and intermolecular distances in
      monomeric and trimeric LHCII, yielding information on the protein structure and
      its local flexibility. A spin label rotamer library based on a molecular dynamics
      simulation was used to take the local mobility of spin labels into account. The
      core of LHCII in solution adopts a structure very similar or identical to the one
      seen in crystallized LHCII trimers with little motional freedom as indicated by
      narrow distance distributions along and between alpha helices. However, distances
      comprising the lumenal loop domain show broader distance distributions,
      indicating some mobility of this loop structure. Positions in the hydrophilic N
      terminal domain, upstream of the first trans-membrane alpha helix, exhibit more
      and more mobility the closer they are to the N terminus. The nine amino acids at
      the very N terminus that have not been resolved in any of the crystal structure
      analyses give rise to very broad and possibly bimodal distance distributions,
      which may represent two families of preferred conformations.

PMID- 22147707
TI  - Insights into high affinity small ubiquitin-like modifier (SUMO) recognition by
      SUMO-interacting motifs (SIMs) revealed by a combination of NMR and peptide array
      analysis.
AB  - The small ubiquitin-like modifiers (SUMOs) regulate many essential cellular
      functions. Only one type of SUMO-interacting motif (SIM) has been identified that
      can extend the beta-sheet of SUMO as either a parallel or an antiparallel strand.
      The molecular determinants of the bound orientation and paralogue specificity of
      a SIM are unclear. To address this question, we have conducted structural studies
      of SUMO1 in complex with a SUMO1-specific SIM that binds to SUMO1 with high
      affinity without post-translational modifications using nuclear magnetic
      resonance methods. In addition, the SIM sequence requirements have been
      investigated by peptide arrays in comparison with another high affinity SIM that
      binds in the opposing orientation. We found that antiparallel binding SIMs
      tolerate more diverse sequences, whereas the parallel binding SIMs prefer the
      more strict sequences consisting of (I/V)DLT that have a preference in high
      affinity SUMO2 and -3 binding. Comparison of two high affinity SUMO1-binding SIMs
      that bind in opposing orientations has revealed common SUMO1-specific
      interactions needed for high affinity binding. This study has significantly
      advanced our understanding of the molecular determinants underlining SUMO-SIM
      recognition.

PMID- 22147708
TI  - Structural and functional insights into the DNA replication factor Cdc45 reveal
      an evolutionary relationship to the DHH family of phosphoesterases.
AB  - Cdc45 is an essential protein conserved in all eukaryotes and is involved both in
      the initiation of DNA replication and the progression of the replication fork.
      With GINS, Cdc45 is an essential cofactor of the Mcm2-7 replicative helicase
      complex. Despite its importance, no detailed information is available on either
      the structure or the biochemistry of the protein. Intriguingly, whereas
      homologues of both GINS and Mcm proteins have been described in Archaea, no
      counterpart for Cdc45 is known. Herein we report a bioinformatic analysis that
      shows a weak but significant relationship among eukaryotic Cdc45 proteins and a
      large family of phosphoesterases that has been described as the DHH family,
      including inorganic pyrophosphatases and RecJ ssDNA exonucleases. These enzymes
      catalyze the hydrolysis of phosphodiester bonds via a mechanism involving two
      Mn(2+) ions. Only a subset of the amino acids that coordinates Mn(2+) is
      conserved in Cdc45. We report biochemical and structural data on the recombinant
      human Cdc45 protein, consistent with the proposed DHH family affiliation. Like
      the RecJ exonucleases, the human Cdc45 protein is able to bind single-stranded,
      but not double-stranded DNA. Small angle x-ray scattering data are consistent
      with a model compatible with the crystallographic structure of the RecJ/DHH
      family members.

PMID- 22147709
TI  - Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R)
      differentially regulates orthosteric but not allosteric agonist binding and
      function.
AB  - The glucagon-like peptide-1 receptor (GLP-1R) is a prototypical family B G
      protein-coupled receptor that exhibits physiologically important pleiotropic
      coupling and ligand-dependent signal bias. In our accompanying article (Koole,
      C., Wootten, D., Simms, J., Miller, L. J., Christopoulos, A., and Sexton, P. M.
      (2012) J. Biol. Chem. 287, 3642-3658), we demonstrate, through alanine-scanning
      mutagenesis, a key role for extracellular loop (ECL) 2 of the receptor in
      propagating activation transition mediated by GLP-1 peptides that occurs in a
      peptide- and pathway-dependent manner for cAMP formation, intracellular
      (Ca(2+)(i)) mobilization, and phosphorylation of extracellular signal-regulated
      kinases 1 and 2 (pERK1/2). In this study, we examine the effect of ECL2 mutations
      on the binding and signaling of the peptide mimetics, exendin-4 and
      oxyntomodulin, as well as small molecule allosteric agonist 6,7-dichloro-2
      methylsulfonyl-3-tert-butylaminoquinoxaline (compound 2). Lys-288, Cys-296, Trp
      297, and Asn-300 were globally important for peptide signaling and also had
      critical roles in governing signal bias of the receptor. Peptide-specific effects
      on relative efficacy and signal bias were most commonly observed for residues 301
      305, although R299A mutation also caused significantly different effects for
      individual peptides. Met-303 was more important for exendin-4 and oxyntomodulin
      action than those of GLP-1 peptides. Globally, ECL2 mutation was more detrimental
      to exendin-4-mediated Ca(2+)i release than GLP-1(7-36)-NH(2), providing
      additional evidence for subtle differences in receptor activation by these two
      peptides. Unlike peptide activation of the GLP-1R, ECL2 mutations had only
      limited impact on compound 2 mediated cAMP and pERK responses, consistent with
      this ligand having a distinct mechanism for receptor activation. These data
      suggest a critical role of ECL2 of the GLP-1R in the activation transition of the
      receptor by peptide agonists.

PMID- 22147710
TI  - Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) has
      a critical role in GLP-1 peptide binding and receptor activation.
AB  - The glucagon-like peptide-1 receptor (GLP-1R) is a therapeutically important
      family B G protein-coupled receptor (GPCR) that is pleiotropically coupled to
      multiple signaling effectors and, with actions including regulation of insulin
      biosynthesis and secretion, is one of the key targets in the management of type
      II diabetes mellitus. However, there is limited understanding of the role of the
      receptor core in orthosteric ligand binding and biological activity. To assess
      involvement of the extracellular loop (ECL) 2 in ligand-receptor interactions and
      receptor activation, we performed alanine scanning mutagenesis of loop residues
      and assessed the impact on receptor expression and GLP-1(1-36)-NH(2) or GLP-1(7
      36)-NH(2) binding and activation of three physiologically relevant signaling
      pathways as follows: cAMP formation, intracellular Ca(2+) (Ca(2+)(i))
      mobilization, and phosphorylation of extracellular signal-regulated kinases 1 and
      2 (pERK1/2). Although antagonist peptide binding was unaltered, almost all
      mutations affected GLP-1 peptide agonist binding and/or coupling efficacy,
      indicating an important role in receptor activation. However, mutation of several
      residues displayed distinct pathway responses with respect to wild type receptor,
      including Arg-299 and Tyr-305, where mutation significantly enhanced both GLP-1(1
      36)-NH(2)- and GLP-1(7-36)-NH(2)-mediated signaling bias for pERK1/2. In
      addition, mutation of Cys-296, Trp-297, Asn-300, Asn-302, and Leu-307
      significantly increased GLP-1(7-36)-NH(2)-mediated signaling bias toward pERK1/2.
      Of all mutants studied, only mutation of Trp-306 to alanine abolished all
      biological activity. These data suggest a critical role of ECL2 of the GLP-1R in
      the activation transition(s) of the receptor and the importance of this region in
      the determination of both GLP-1 peptide- and pathway-specific effects.

PMID- 22147711
TI  - Increasing prevalence of knee pain and symptomatic knee osteoarthritis: survey
      and cohort data.
AB  - BACKGROUND: A recent surge in knee replacements is assumed to be due to aging and
      increased obesity of the U.S. population. OBJECTIVE: To assess whether age,
      obesity, and change in radiographic knee osteoarthritis explain the trend in knee
      pain and osteoarthritis. DESIGN: Cross-sectional, using data from 6 NHANES
      (National Health and Nutrition Examination Survey) surveys between 1971 and 2004
      and from 3 examination periods in the FOA (Framingham Osteoarthritis) Study
      between 1983 through 2005. SETTING: U.S. population. PARTICIPANTS: NHANES
      participants (white or African American; aged 60 to 74 years) and FOA Study
      participants (mostly white; aged >=70 years) were included. MEASUREMENTS: NHANES
      participants were asked about pain in or around the knee on most days. In the FOA
      Study, participants were asked about knee pain and had bilateral weight-bearing
      anteroposterior knee radiography to define radiographic knee osteoarthritis.
      Radiographic evidence and self-reported pain were used to define symptomatic knee
      osteoarthritis. The age- and age- and body mass index (BMI)-adjusted prevalences
      of knee pain and osteoarthritis at later examinations were compared with that of
      earlier examinations by using the ratio of the prevalence estimates. RESULTS: Age
      and BMI-adjusted prevalence of knee pain increased by about 65% in NHANES from
      1974 to 1994 among non-Hispanic white and Mexican American men and women and
      among African American women. In the FOA Study, the age- and BMI-adjusted
      prevalence of knee pain and symptomatic knee osteoarthritis approximately doubled
      in women and tripled in men over 20 years. No such trend was observed in the
      prevalence of radiographic knee osteoarthritis in FOA Study participants. After
      age adjustment, additional adjustment for BMI resulted in a 10% to 25% decrease
      in the prevalence ratios for knee pain and symptomatic knee osteoarthritis.
      LIMITATIONS: Differences in sampling of FOA Study participants over time or birth
      cohort effects cannot be ruled out as possible explanations of the increased
      reporting of knee pain. Increases in prevalence at the last interval in the FOA
      Study might be due to differences in cohort membership by interval. CONCLUSION:
      Results suggest that the prevalence of knee pain has increased substantially over
      20 years, independent of age and BMI. Obesity accounted for only part of this
      increase. Symptomatic knee osteoarthritis increased but radiographic knee
      osteoarthritis did not. PRIMARY FUNDING SOURCE: American College of Rheumatology
      Research and Education Foundation and National Institutes of Health. The FOA
      Study was funded by the National Heart, Lung, and Blood Institute (for the parent
      Framingham Heart Study), National Institute on Aging, and National Institute of
      Arthritis and Musculoskeletal and Skin Diseases (FOA Study), National Institutes
      of Health.

PMID- 22147712
TI  - Maternal immune response and neonatal seroprotection from a single dose of a
      monovalent nonadjuvanted 2009 influenza A(H1N1) vaccine: a single-group trial.
AB  - BACKGROUND: Pregnant women and infants who get influenza are at increased risk
      for severe illness. OBJECTIVE: To evaluate the immunogenicity and transplacental
      antibody transfer of 2009 pandemic influenza A(H1N1) vaccine administered during
      pregnancy. DESIGN: Prospective, multicenter, single-group clinical trial.
      (ClinicalTrials.gov registration number: NCT01024400) SETTING: Five level-3
      perinatal centers in France. PATIENTS: 107 pregnant women between 22(0/7) and
      32(0/7) weeks of gestation. INTERVENTION: An intramuscular dose of a
      nonadjuvanted H1N1 vaccine that contained 15 mcg of hemagglutinin. MEASUREMENTS:
      Proportion of women with an influenza antibody titer of 1:40 or greater at days
      21 and 42 after vaccination, delivery, and 3 months after delivery.
      Seroconversion rate, fold increase in the geometric mean titer 21 days after
      vaccination, and proportion of neonates with an antibody titer of 1:40 or greater
      at birth were also assessed. RESULTS: At baseline, 19% of the women had an
      antibody titer of 1:40 or greater. At day 21, 98% of the women had an antibody
      titer of 1:40 or greater, the seroconversion rate was 93%, and the fold increase
      in geometric mean titer was 67.4. At day 42, delivery, and 3 months after
      delivery, 98%, 92%, and 90% of the women, respectively, had an antibody titer of
      1:40 or greater. Ninety-five percent of the cord serum samples obtained from 88
      neonates showed an antibody titer of 1:40 or greater. The median neonate-mother
      antibody titer ratio was 1.4. LIMITATIONS: Only healthy pregnant women were
      selected. Data on hemagglutination inhibition antibody titers of infants were
      reported only at birth. CONCLUSION: A single dose of a nonadjuvanted influenza
      A(H1N1) vaccine with 15 mcg of hemagglutinin triggered a strong immune response
      in pregnant women and a high rate of neonatal seroprotection. PRIMARY FUNDING
      SOURCE: French National Institute of Health and Medical Research.

PMID- 22147713
TI  - Association of high-density lipoprotein cholesterol with incident cardiovascular
      events in women, by low-density lipoprotein cholesterol and apolipoprotein B100
      levels: a cohort study.
AB  - BACKGROUND: Prior studies have found inverse associations between high-density
      lipoprotein cholesterol (HDL-C) or apolipoprotein A-I levels and cardiovascular
      disease (CVD). Whether this observation is consistent across low-density
      lipoprotein cholesterol (LDL-C) levels or total atherogenic particle burden
      (apolipoprotein B100) is less well-studied, particularly in women. OBJECTIVE: To
      determine the association between HDL-C or apolipoprotein A-I level and CVD
      across a range of LDL-C and apolipoprotein B100 values. DESIGN: Prospective
      cohort study. SETTING: The Women's Health Study, a cohort of U.S. female health
      professionals. PARTICIPANTS: 26,861 initially healthy women, aged 45 years or
      older at study entry (1992-1995), who were followed for a mean of approximately
      11 years. MEASUREMENTS: Baseline lipids were measured directly, and
      apolipoproteins were measured with immunoassays. Outcomes were incident total CVD
      (n = 929), coronary events (n = 602), and stroke (n = 319). RESULTS: In
      multivariable analyses, HDL-C and apolipoprotein A-I levels were inversely
      associated with CVD and coronary events but not stroke. Adjusted coronary hazard
      ratios for decreasing quintiles of HDL-C were 1.00 (reference), 1.23 (95% CI,
      0.85 to 1.78), 1.42 (CI, 0.98 to 2.06), 1.90 (CI, 1.33 to 2.71), and 2.19 (CI,
      1.51 to 3.19) (P for linear trend < 0.001); corresponding hazard ratios for
      apolipoprotein A-I were 1.00 (reference), 0.98 (CI, 0.71 to 1.35), 1.02 (CI, 0.72
      to 1.44), 1.37 (CI, 0.98 to 1.90), and 1.58 (CI, 1.14 to 2.20) (P for linear
      trend = 0.005). Consistent inverse associations were found for HDL-C with
      coronary events across a range of LDL-C values, including among women with low
      LDL-C levels. No associations were noted for HDL-C or apolipoprotein A-I among
      women with low apolipoprotein B100 values (<0.90 g/L). LIMITATION: Participants
      were at low risk for CVD, the number of events in the lowest apolipoprotein B100
      stratum was small, only a single baseline measurement was obtained, and residual
      confounding may have occurred. CONCLUSION: Consistent inverse associations were
      found for HDL-C with incident coronary events among women with a range of LDL-C
      values. Among women with low total atherogenic particle burden (apolipoprotein
      B100 level <0.90 g/L), few events occurred and no associations were seen. PRIMARY
      FUNDING SOURCE: Merck & Co. and the National Heart, Lung, and Blood Institute and
      National Cancer Institute, National Institutes of Health.

PMID- 22147714
TI  - Cost-effectiveness of different screening strategies for osteoporosis in
      postmenopausal women.
AB  - BACKGROUND: The best strategies to screen postmenopausal women for osteoporosis
      are not clear. OBJECTIVE: To identify the cost-effectiveness of various screening
      strategies. DESIGN: Individual-level state-transition cost-effectiveness model.
      DATA SOURCES: Published literature. TARGET POPULATION: U.S. women aged 55 years
      or older. TIME HORIZON: Lifetime. PERSPECTIVE: Payer. INTERVENTION: Screening
      strategies composed of alternative tests (central dual-energy x-ray
      absorptiometry [DXA], calcaneal quantitative ultrasonography [QUS], and the
      Simple Calculated Osteoporosis Risk Estimation [SCORE] tool) initiation ages,
      treatment thresholds, and rescreening intervals. Oral bisphosphonate treatment
      was assumed, with a base-case adherence rate of 50% and a 5-year on/off treatment
      pattern. OUTCOME MEASURES: Incremental cost-effectiveness ratios (2010 U.S.
      dollars per quality-adjusted life-year [QALY] gained). RESULTS OF BASE-CASE
      ANALYSIS: At all evaluated ages, screening was superior to not screening. In
      general, quality-adjusted life-days gained with screening tended to increase with
      age. At all initiation ages, the best strategy with an incremental cost
      effectiveness ratio (ICER) of less than $50,000 per QALY was DXA screening with a
      T-score threshold of -2.5 or less for treatment and with follow-up screening
      every 5 years. Across screening initiation ages, the best strategy with an ICER
      less than $50,000 per QALY was initiation of screening at age 55 years by using
      DXA -2.5 with rescreening every 5 years. The best strategy with an ICER less than
      $100,000 per QALY was initiation of screening at age 55 years by using DXA with a
      T-score threshold of -2.0 or less for treatment and then rescreening every 10
      years. No other strategy that involved treatment of women with osteopenia had an
      ICER less than $100,000 per QALY. Many other strategies, including strategies
      with SCORE or QUS prescreening, were also cost-effective, and in general the
      differences in effectiveness and costs between evaluated strategies was small.
      RESULTS OF SENSITIVITY ANALYSIS: Probabilistic sensitivity analysis did not
      reveal a consistently superior strategy. LIMITATIONS: Data were primarily from
      white women. Screening initiation at ages younger than 55 years were not
      examined. Only osteoporotic fractures of the hip, vertebrae, and wrist were
      modeled. CONCLUSION: Many strategies for postmenopausal osteoporosis screening
      are effective and cost-effective, including strategies involving screening
      initiation at age 55 years. No strategy substantially outperforms another.
      PRIMARY FUNDING SOURCE: National Center for Research Resources.

PMID- 22147715
TI  - Comparative benefits and harms of second-generation antidepressants for treating
      major depressive disorder: an updated meta-analysis.
AB  - BACKGROUND: Second-generation antidepressants dominate the management of major
      depressive disorder (MDD), but evidence on the comparative benefits and harms of
      these agents is contradictory. PURPOSE: To compare the benefits and harms of
      second-generation antidepressants for treating MDD in adults. DATA SOURCES:
      English-language studies from PubMed, Embase, the Cochrane Library, PsycINFO, and
      International Pharmaceutical Abstracts from 1980 to August 2011 and reference
      lists of pertinent review articles and gray literature. STUDY SELECTION: 2
      independent reviewers identified randomized trials of at least 6 weeks' duration
      to evaluate efficacy and observational studies with at least 1000 participants to
      assess harm. DATA EXTRACTION: Reviewers abstracted data about study design and
      conduct, participants, and interventions and outcomes and rated study quality. A
      senior reviewer checked and confirmed extracted data and quality ratings. DATA
      SYNTHESIS: Meta-analyses and mixed-treatment comparisons of response to treatment
      and weighted mean differences were conducted on specific scales to rate
      depression. On the basis of 234 studies, no clinically relevant differences in
      efficacy or effectiveness were detected for the treatment of acute, continuation,
      and maintenance phases of MDD. No differences in efficacy were seen in patients
      with accompanying symptoms or in subgroups based on age, sex, ethnicity, or
      comorbid conditions. Individual drugs differed in onset of action, adverse
      events, and some measures of health-related quality of life. LIMITATIONS: Most
      trials were conducted in highly selected populations. Publication bias might
      affect the estimates of some comparisons. Mixed-treatment comparisons cannot
      conclusively exclude differences in efficacy. Evidence within subgroups was
      limited. CONCLUSION: Current evidence does not warrant recommending a particular
      second-generation antidepressant on the basis of differences in efficacy.
      Differences in onset of action and adverse events may be considered when choosing
      a medication. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 22147716
TI  - Knee pain and osteoarthritis: lessons learned and lessons to be learned.

PMID- 22147717
TI  - Comparative effectiveness and cost-effectiveness of strategies to screen for
      osteoporosis in postmenopausal women.

PMID- 22147718
TI  - Who lives, who dies.

PMID- 22147719
TI  - Images of healing.

PMID- 22147720
TI  - Communicating benefits and harms of treatment.

PMID- 22147721
TI  - Low health literacy.

PMID- 22147722
TI  - Low health literacy.

PMID- 22147723
TI  - Low health literacy.

PMID- 22147724
TI  - Low health literacy.

PMID- 22147725
TI  - Risk for complications after transthoracic needle lung biopsy.

PMID- 22147726
TI  - Summaries for patients. Trends in knee pain and knee osteoarthritis.

PMID- 22147727
TI  - Summaries for patients. Influenza vaccine to protect mothers and their babies.

PMID- 22147728
TI  - Summaries for patients. Does low-density lipoprotein cholesterol influence the
      relationship between high-density lipoprotein cholesterol and cardiovascular risk
      in women?

PMID- 22147729
TI  - In the clinic. Hip fracture.

PMID- 22147730
TI  - Functional proteomics establishes the interaction of SIRT7 with chromatin
      remodeling complexes and expands its role in regulation of RNA polymerase I
      transcription.
AB  - Among mammalian sirtuins, SIRT7 is the only enzyme residing in nucleoli where
      ribosomal DNA is transcribed. Recent reports established that SIRT7 associates
      with RNA Pol I machinery and is required for rDNA transcription. Although defined
      by its homology to the yeast histone deacetylase Sir2, current knowledge suggests
      that SIRT7 itself has little to no deacetylase activity. Because only two SIRT7
      interactions have been thus far described: RNA Pol I and upstream binding factor,
      identification of proteins and complexes associating with SIRT7 is critical to
      understanding its functions. Here, we present the first characterization of SIRT7
      interaction networks. We have systematically investigated protein interactions of
      three EGFP-tagged SIRT7 constructs: wild type, a point mutation affecting rDNA
      transcription, and a deletion mutant lacking the predicted coiled-coil domain. A
      combinatorial proteomics and bioinformatics approach was used to integrate gene
      ontology classifications, functional protein networks, and normalized abundances
      of proteins co-isolated with SIRT7. The resulting refined proteomic data set
      confirmed SIRT7 interactions with RNA Pol I and upstream binding factor and
      highlighted association with factors involved in RNA Pol I- and II-dependent
      transcriptional processes and several nucleolus-localized chromatin remodeling
      complexes. Particularly enriched were members of the B-WICH complex, such as
      Mybbp1a, WSTF, and SNF2h. Prominent interactions were validated by a selected
      reaction monitoring-like approach using metabolic labeling with stable isotopes,
      confocal microscopy, reciprocal immunoaffinity precipitation, and co-isolation
      with endogenous SIRT7. To extend the current knowledge of mechanisms involved in
      SIRT7-dependent regulation of rDNA transcription, we showed that small
      interfering RNA-mediated SIRT7 knockdown leads to reduced levels of RNA Pol I
      protein, but not messenger RNA, which was confirmed in diverse cell types. The
      down-regulation of RNA Pol I protein levels placed in the context of SIRT7
      interaction networks led us to propose that SIRT7 plays a crucial role in
      connecting the function of chromatin remodeling complexes to RNA Pol I machinery
      during transcription.

PMID- 22147732
TI  - Extensive determination of glycan heterogeneity reveals an unusual abundance of
      high mannose glycans in enriched plasma membranes of human embryonic stem cells.
AB  - Most cell membrane proteins are known or predicted to be glycosylated in
      eukaryotic organisms, where surface glycans are essential in many biological
      processes including cell development and differentiation. Nonetheless, the
      glycosylation on cell membranes remains not well characterized because of the
      lack of sensitive analytical methods. This study introduces a technique for the
      rapid profiling and quantitation of N- and O-glycans on cell membranes using
      membrane enrichment and nanoflow liquid chromatography/mass spectrometry of
      native structures. Using this new method, the glycome analysis of cell membranes
      isolated from human embryonic stem cells and somatic cell lines was performed.
      Human embryonic stem cells were found to have high levels of high mannose
      glycans, which contrasts with IMR-90 fibroblasts and a human normal breast cell
      line, where complex glycans are by far the most abundant and high mannose glycans
      are minor components. O-Glycosylation affects relatively minor components of cell
      surfaces. To verify the quantitation and localization of glycans on the human
      embryonic stem cell membranes, flow cytometry and immunocytochemistry were
      performed. Proteomics analyses were also performed and confirmed enrichment of
      plasma membrane proteins with some contamination from endoplasmic reticulum and
      other membranes. These findings suggest that high mannose glycans are the major
      component of cell surface glycosylation with even terminal glucoses. High mannose
      glycans are not commonly presented on the surfaces of mammalian cells or in serum
      yet may play important roles in stem cell biology. The results also mean that
      distinguishing stem cells from other mammalian cells may be facilitated by the
      major difference in the glycosylation of the cell membrane. The deep structural
      analysis enabled by this new method will enable future mechanistic studies on the
      biological significance of high mannose glycans on stem cell membranes and
      provide a general tool to examine cell surface glycosylation.

PMID- 22147731
TI  - Protein expression signatures for inhibition of epidermal growth factor receptor
      mediated signaling.
AB  - Analysis of cellular signaling networks typically involves targeted measurements
      of phosphorylated protein intermediates. However, phosphoproteomic analyses
      usually require affinity enrichment of phosphopeptides and can be complicated by
      artifactual changes in phosphorylation caused by uncontrolled preanalytical
      variables, particularly in the analysis of tissue specimens. We asked whether
      changes in protein expression, which are more stable and easily analyzed, could
      reflect network stimulation and inhibition. We employed this approach to analyze
      stimulation and inhibition of the epidermal growth factor receptor (EGFR) by EGF
      and selective EGFR inhibitors. Shotgun analysis of proteomes from proliferating
      A431 cells, EGF-stimulated cells, and cells co-treated with the EGFR inhibitors
      cetuximab or gefitinib identified groups of differentially expressed proteins.
      Comparisons of these protein groups identified 13 proteins whose EGF-induced
      expression changes were reversed by both EGFR inhibitors. Targeted multiple
      reaction monitoring analysis verified differential expression of 12 of these
      proteins, which comprise a candidate EGFR inhibition signature. We then tested
      these 12 proteins by multiple reaction monitoring analysis in three other models:
      1) a comparison of DiFi (EGFR inhibitor-sensitive) and HCT116 (EGFR-insensitive)
      cell lines, 2) in formalin-fixed, paraffin-embedded mouse xenograft DiFi and
      HCT116 tumors, and 3) in tissue biopsies from a patient with the gastric
      hyperproliferative disorder Menetrier's disease who was treated with cetuximab.
      Of the proteins in the candidate signature, a core group, including c-Jun, Jagged
      1, and Claudin 4, were decreased by EGFR inhibitors in all three models. Although
      the goal of these studies was not to validate a clinically useful EGFR inhibition
      signature, the results confirm the hypothesis that clinically used EGFR
      inhibitors generate characteristic protein expression changes. This work further
      outlines a prototypical approach to derive and test protein expression signatures
      for drug action on signaling networks.

PMID- 22147733
TI  - Metabolic switches and adaptations deduced from the proteomes of Streptomyces
      coelicolor wild type and phoP mutant grown in batch culture.
AB  - Bacteria in the genus Streptomyces are soil-dwelling oligotrophs and important
      producers of secondary metabolites. Previously, we showed that global messenger
      RNA expression was subject to a series of metabolic and regulatory switches
      during the lifetime of a fermentor batch culture of Streptomyces coelicolor M145.
      Here we analyze the proteome from eight time points from the same fermentor
      culture and, because phosphate availability is an important regulator of
      secondary metabolite production, compare this to the proteome of a similar time
      course from an S. coelicolor mutant, INB201 (DeltaphoP), defective in the control
      of phosphate utilization. The proteomes provide a detailed view of enzymes
      involved in central carbon and nitrogen metabolism. Trends in protein expression
      over the time courses were deduced from a protein abundance index, which also
      revealed the importance of stress pathway proteins in both cultures. As expected,
      the DeltaphoP mutant was deficient in expression of PhoP-dependent genes, and
      several putatively compensatory metabolic and regulatory pathways for phosphate
      scavenging were detected. Notably there is a succession of switches that
      coordinately induce the production of enzymes for five different secondary
      metabolite biosynthesis pathways over the course of the batch cultures.

PMID- 22147735
TI  - Influence of race, insurance, socioeconomic status, and hospital type on receipt
      of guideline-concordant adjuvant systemic therapy for locoregional breast
      cancers.
AB  - PURPOSE: For breast cancer, guidelines direct the delivery of adjuvant systemic
      therapy on the basis of lymph node status, histology, tumor size, grade, and
      hormonal receptor status. We explored how race/ethnicity, insurance, census tract
      level poverty and education, and hospital Commission on Cancer (CoC) status were
      associated with the receipt of guideline-concordant adjuvant systemic therapy.
      METHODS: Locoregional breast cancers diagnosed in 2004 (n = 6,734) were from the
      National Program of Cancer Registries-funded seven-state Patterns of Care study
      of the Centers for Disease Control and Prevention. Predictors of guideline
      concordant (receiving/not receiving) adjuvant systemic therapy, according to
      National Comprehensive Cancer Network Guidelines, were explored by logistic
      regression. RESULTS: Overall, 35% of women received nonguideline chemotherapy,
      12% received nonguideline regimens, and 20% received nonguideline hormonal
      therapy. Significant predictors of nonguideline chemotherapy included Medicaid
      insurance (odds ratio [OR], 0.66; 95% CI, 0.50 to 0.86), high-poverty areas (OR,
      0.77; 95% CI, 0.62 to 0.96), and treatment at non-CoC hospitals (OR, 0.69; 95%
      CI, 0.56 to 0.85), with adjustment for age, registry, and clinical variables.
      Predictors of nonguideline regimens among chemotherapy recipients included lack
      of insurance (OR, 0.47; 95% CI, 0.25 to 0.92), high-poverty areas (OR, 0.71; 95%
      CI, 0.51 to 0.97), and low-education areas (OR, 0.65; 95% CI, 0.48 to 0.89) after
      adjustment. Living in high-poverty areas (OR, 0.78; 95% CI, 0.64 to 0.96) and
      treatment at non-CoC hospitals (OR, 0.68; 95% CI, 0.55 to 0.83) predicted
      nonguideline hormonal therapy after adjustment. ORs for poverty, education, and
      insurance were attenuated in the full models. CONCLUSION: Sociodemographic and
      hospital factors are associated with guideline-concordant use of systemic therapy
      for breast cancer. The identification of modifiable factors that lead to
      nonguideline treatment may reduce disparities in breast cancer survival.

PMID- 22147734
TI  - Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small
      intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort
      Consortium.
AB  - BACKGROUND: The evidence for a role of tobacco smoking, alcohol drinking, and
      body mass index (BMI) in the etiology of small intestine cancer is based mainly
      on case-control studies from Europe and United States. SUBJECTS AND METHODS: We
      harmonized the data across 12 cohort studies from mainland China, Japan, Korea,
      Singapore, and Taiwan, comprising over 500,000 subjects followed for an average
      of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men)
      tobacco smoking and alcohol drinking. RESULTS: A total of 134 incident cases were
      observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of
      unknown histology). There was a statistically non-significant trend toward
      increased HR in subjects with high BMI [HR for BMI>27.5 kg/m2, compared with 22.6
      25.0, 1.50; 95% confidence interval (CI) 0.76-2.96]. No association was suggested
      for tobacco smoking; men drinking>400 g of ethanol per week had an HR of 1.57
      (95% CI 0.66-3.70), compared with abstainers. CONCLUSIONS: Our study supports the
      hypothesis that elevated BMI may be a risk factor for small intestine cancer. An
      etiologic role of alcohol drinking was suggested. Our results reinforce the
      existing evidence that the epidemiology of small intestine cancer resembles that
      of colorectal cancer.

PMID- 22147736
TI  - Clinical cancer advances 2011: Annual Report on Progress Against Cancer from the
      American Society of Clinical Oncology.
AB  - A message from ASCO'S President. It has been forty years since President Richard
      Nixon signed the National Cancer Act of 1971, which many view as the nation's
      declaration of the "War on Cancer." The bill has led to major investments in
      cancer research and significant increases in cancer survival. Today, two-thirds
      of patients survive at least five years after being diagnosed with cancer
      compared with just half of all diagnosed patients surviving five years after
      diagnosis in 1975. The research advances detailed in this year's Clinical Cancer
      Advances demonstrate that improvements in cancer screening, treatment, and
      prevention save and improve lives. But although much progress has been made,
      cancer remains one of the world's most serious health problems. In the United
      States, the disease is expected to become the nation's leading cause of death in
      the years ahead as our population ages. I believe we can accelerate the pace of
      progress, provided that everyone involved in cancer care works together to
      achieve this goal. It is this viewpoint that has shaped the theme for my
      presidential term: Collaborating to Conquer Cancer. In practice, this means that
      physicians and researchers must learn from every patient's experience, ensure
      greater collaboration between members of a patient's medical team, and involve
      more patients in the search for cures through clinical trials. Cancer advocates,
      insurers, and government agencies also have important roles to play. Today, we
      have an incredible opportunity to improve the quality of cancer care by drawing
      lessons from the real-world experiences of patients. The American Society of
      Clinical Oncology (ASCO) is taking the lead in this area, in part through
      innovative use of health information technology. In addition to our existing
      quality initiatives, ASCO is working with partners to develop a comprehensive
      rapid-learning system for cancer care. When complete, this system will provide
      physicians with personalized, real-time information that can inform the care of
      every patient with cancer as well as connect patients with their entire medical
      teams. The rapid learning system will form a continuous cycle of learning:
      securely capturing data from every patient at the point of care, drawing on
      evidence-based guidelines, and evaluating quality of care against those standards
      and the outcomes of other patients. Clinical trials are another area in which
      collaboration is critical. Increasing clinical trial participation will require
      commitment across the cancer community from physicians, patients, insurers,
      hospitals, and industry. A 2010 report by the Institute of Medicine described
      challenges to participation in trials by both physicians and patients and
      provided recommendations for revitalizing clinical trials conducted through the
      National Cancer Institute's Cooperative Group Program. ASCO has pledged its
      support for the full implementation of these recommendations. More broadly, ASCO
      recently outlined a bold vision for translational and clinical cancer research
      for the next decade and made recommendations to achieve that vision. Accelerating
      Progress Against Cancer: ASCO's Blueprint for Transforming Clinical and
      Translational Research, released in November, calls for a research system that
      takes full advantage of today's scientific and technologic opportunities and sets
      a high-level agenda for policy makers, regulators, and advocates. Cancer research
      has transformed cancer care in the past forty years, and this year's Clinical
      Cancer Advances illustrates how far we have come in the past year alone. We now
      have a tremendous opportunity to use today's knowledge and collaborate across all
      facets of cancer care to conquer this deadly disease. Michael P. Link, MD
      President American Society of Clinical Oncology.

PMID- 22147737
TI  - Nonmalignant late effects and compromised functional status in survivors of
      hematopoietic cell transplantation.
AB  - PURPOSE: Our objective was to describe the incidence of nonmalignant late
      complications and their association with health and functional status in a recent
      cohort of hematopoietic cell transplantation (HCT) survivors. PATIENTS AND
      METHODS: We determined the incidence of 14 nonmalignant late effects in adults
      who underwent transplantation from January 2004 through June 2009 at Fred
      Hutchinson Cancer Research Center who survived at least 1 year after HCT. Data
      were derived from review of medical records and annual self-reported
      questionnaires. RESULTS: The 1,087 survivors in the study had a median age at HCT
      of 53 years (range, 21 to 78 years) and were followed for a median of 37 months
      (range, 12 to 77 months) after HCT. The prevalence of pre-existing conditions
      ranged from 0% to 9.8%. The cumulative incidence of any nonmalignant late effect
      at 5 years after HCT was 44.8% among autologous and 79% among allogeneic
      recipients; 2.5% of autologous and 25.5% of allogeneic recipients had three or
      more late effects. Survivors with three or more late effects had lower physical
      functioning and Karnofsky score, lower likelihood of full-time work or study, and
      a higher likelihood of having limitations in usual activities. Predictors of at
      least one late effect were age >= 50 years, female sex, and unrelated donor, but
      not the intensity of the conditioning regimen. CONCLUSION: The burden of
      nonmalignant late effects after HCT is high, even with modern treatments and
      relatively short follow-up. These late effects are associated with poor health
      and functional status, underscoring the need for close follow-up of this group
      and additional research to address these complications.

PMID- 22147738
TI  - Takotsubo cardiomyopathy and Fluorouracil: case report and review of the
      literature.

PMID- 22147739
TI  - Role of nonclinical factors in the receipt of high-quality systemic adjuvant
      breast cancer treatment.

PMID- 22147740
TI  - Multimodal therapy of an intramedullary cervical primitive neuroectodermal tumor
      in an adult.

PMID- 22147741
TI  - Should all women with breast cancer be tested for BRCA mutations at the time of
      diagnosis?

PMID- 22147742
TI  - Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an International
      Prospective Breast Cancer Family Registry population-based cohort study.
AB  - PURPOSE: To compare breast cancer prognosis in BRCA1 and BRCA2 mutation carriers
      with that in patients with sporadic disease. PATIENTS AND METHODS: An
      international population-based cohort study was conducted in Canada, the United
      States, and Australia of 3,220 women with incident breast cancer diagnosed
      between 1995 and 2000 and observed prospectively. Ninety-three had BRCA1
      mutations; 71, BRCA2 mutations; one, both mutations; 1,550, sporadic breast
      cancer; and 1,505, familial breast cancer (without known BRCA1 or BRCA2
      mutation). Distant recurrence and death were analyzed. RESULTS: Mean age at
      diagnosis was 45.3 years; mean follow-up was 7.9 years. Risks of distant
      recurrence and death did not differ significantly between BRCA1 mutation carriers
      and those with sporadic disease in univariable and multivariable analyses. Risk
      of distant recurrence was higher for BRCA2 mutation carriers compared with those
      with sporadic disease in univariable analysis (hazard ratio [HR], 1.63; 95% CI,
      1.02 to 2.60; P = .04). Risk of death was also higher in BRCA2 carriers in
      univariable analysis (HR, 1.81; 95% CI, 1.15 to 2.86; P = .01). After adjustment
      for age, tumor stage and grade, nodal status, hormone receptors, and year of
      diagnosis, no differences were observed for distant recurrence (HR, 1.00; 95% CI,
      0.62 to 1.61; P = 1.00) or death (HR, 1.12; 95% CI, 0.70 to 1.79; P = .64).
      CONCLUSION: Outcomes of BRCA1 mutation carriers were similar to those of patients
      with sporadic breast cancer. Worse outcomes in BRCA2 mutation carriers in
      univariable analysis seem to reflect the presence of more adverse tumor
      characteristics in these carriers. Similar outcomes were identified in BRCA2
      carriers and those with sporadic disease in multivariable analyses.

PMID- 22147743
TI  - Maximizing the efficacy of angiogenesis inhibitors.

PMID- 22147744
TI  - Ethics, human rights and HIV vaccine trials in low-income settings.
AB  - The massive growth in global health research in past decades has posed many
      challenges for its effective ethical oversight, not least of which is how best to
      provide effective protection of research participants. The extent of the HIV
      epidemic in sub-Saharan Africa in particular makes research into prevention
      technologies for HIV, including HIV vaccine research, a global priority. However,
      the need for vaccine research must be considered in conjunction with the
      individual's right to informed consent, which is based on the principle of
      respect for autonomy. One of the primary human rights violations likely to occur
      in the context of HIV vaccine research is that potential research participants
      may not fully understand what participation in research studies entails. People
      who elect to enrol in HIV vaccine trials are required to understand both the
      potential negative effects of participation (eg, discrimination) as well as
      complex scientific concepts such as randomisation and prophylaxis in order to be
      ethically enrolled. In this study, two vignettes are presented to illustrate two
      core issues in conducting phase III HIV vaccine trials in low-income countries
      namely, (1) from the perspective of participants, the extent to which
      understanding is a prerequisite for consenting to participate in a trial, and (2)
      from the perspective of trial investigators, whether it is appropriate to
      persuade eligible people to enrol in a trial, even though their initial reaction
      is to decline to participate. These vignettes are used to analyse these issues
      through the prisms of research ethics and human rights in order to identify
      helpful synergies. It is argued that the human rights perspective provides a
      helpful lens on ethical issues.

PMID- 22147745
TI  - HEEADSSS assessment for adolescents requiring anticoagulation therapy.
AB  - The care of adolescents with complex chronic illness needs to be developmentally
      appropriate to encourage adherence, knowledge retention and self-management.
      There has been an increase in the number of adolescents requiring long-term or
      lifelong anticoagulation therapy, related to either an underlying illness or
      idiopathic deep vein thrombosis. The burden of anticoagulant therapy, the
      associated risks and the required lifestyle changes can significantly impact on
      psychosocial well-being in the adolescent patient. This review identifies issues
      pertinent to adolescent anticoagulation management and discusses strategies to
      support optimal management. The HEEADSSS (Home, Education and employment, Eating,
      Activities with peers, Drugs, Sexual activity, Suicide and depression, and
      Safety) framework was used to provide guidance in undertaking a psychosocial
      assessment of adolescents requiring anticoagulant therapy in conjunction with a
      structured education strategy. Adolescent anticoagulant management strategies
      employing developmentally appropriate assessment and education will likely result
      in improved therapeutic outcomes for the patient and potentially facilitate
      transition to adult-based care.

PMID- 22147746
TI  - Higher rates of behavioural and emotional problems at preschool age in children
      born moderately preterm.
AB  - OBJECTIVE: To compare preschool children born moderately preterm (MP; 32-35
      weeks' gestation) and children born at term (38-41 weeks' gestation) regarding
      the occurrence of behavioural and emotional problems, overall, for separate types
      of problems and by gender. DESIGN: Prospective cohort study consisting of a
      community-based sample of MP and a random sample of term-born children in 13
      Preventive Child Healthcare centres throughout the Netherlands. PATIENTS: 995 MP
      and 577 term-born children just under age 4 were included. MAIN OUTCOME MEASURES:
      Behavioural and emotional problems were measured using the Child Behavior
      Checklist 1.5-5 years. Seven syndrome scales, internalising, externalising and
      total problems were determined. Higher scores indicate worse outcomes. RESULTS:
      MP children had higher scores on all syndrome scales, internalising,
      externalising and total problems than term-born controls. The mean difference on
      total problems was 4.04 (95% CI 2.08 to 6.00). Prevalence rates of elevated
      externalising problem scores were highest in boys (10.5%) and internalising
      problems were highest in girls (9.9%). MP children were at greater risk for
      somatic complaints (OR 1.92, 95% CI 1.09 to 3.38), internalising (OR 2.40, 95% CI
      1.48 to 3.87), externalising (OR 1.69, 95% CI 1.07 to 2.67) and total problems
      (OR 1.84, 95% CI 1.12 to 3.00). CONCLUSIONS: Moderate preterm birth affects all
      domains of behavioural and emotional problems, particularly for girls. MP
      children should be targeted for the prevention of mental health problems as they
      have a great impact on developmental and social competencies at school and in the
      community.

PMID- 22147747
TI  - Therapeutic mechanism and efficacy of the antibody-drug conjugate BAY 79-4620
      targeting human carbonic anhydrase 9.
AB  - Carbonic anhydrase IX (CAIX) is a cell surface glycoprotein that is expressed in
      many different tumors and yet restricted in normal tissues to the
      gastrointestinal tract. It is upregulated by hypoxia and correlates with tumor
      grade and poor survival in several tumor indications. Monoclonal antibodies (mAb)
      with single digit nanomolar binding affinity for CAIX were derived by panning
      with the recombinant ectodomain of CAIX against the MorphoSys HUCAL Gold library
      of human Fabs. Highest affinity Fabs were converted to full-length IgGs and
      subjected to further characterization based upon their avidity and selectivity
      for CAIX, their capacity to undergo internalization in CAIX-expressing cell
      lines, and their selective localization to CAIX-positive human xenografted tumors
      when administered to mice as fluorescent conjugates. Through this selection
      process, the 3ee9 mAb was identified, which upon conjugation to monomethyl
      auristatin E through a self-immolative enzyme-cleavable linker yielded the potent
      and selective CAIX antibody-drug conjugate CAIX-ADC (BAY 79-4620). In preclinical
      human xenograft models in mice representing several tumor indications, BAY 79
      4620 showed potent antitumor efficacy and in some models showed partial and
      complete tumor shrinkage even following a single dose. The mechanism of action
      was shown by histology to involve the sequelae of events typical of antitubulin
      agents. Efficacy in murine preclinical models correlated semiquantitatively, with
      CAIX expression levels as determined by immunohistochemistry and ELISA. These
      preclinical data collectively support the development of BAY 79-4620 for the
      treatment of cancer patients with CAIX overexpressing tumors.

PMID- 22147748
TI  - Molecular and cellular pharmacology of the hypoxia-activated prodrug TH-302.
AB  - TH-302 is a 2-nitroimidazole triggered hypoxia-activated prodrug (HAP) of bromo
      isophosphoramide mustard currently undergoing clinical evaluation. Here, we
      describe broad-spectrum activity, hypoxia-selective activation, and mechanism of
      action of TH-302. The concentration and time dependence of TH-302 activation was
      examined as a function of oxygen concentration, with reference to the prototypic
      HAP tirapazamine, and showed superior oxygen inhibition of cytotoxicity and much
      improved dose potency relative to tirapazamine. Enhanced TH-302 cytotoxicity
      under hypoxia was observed across 32 human cancer cell lines. One-electron
      reductive enzyme dependence was confirmed using cells overexpressing human
      NADPH:cytochrome P450 oxidoreductase and radiolytic reduction established the
      single-electron stoichiometry of TH-302 fragmentation (activation). Examining
      downstream effects of TH-302 activity, we observed hypoxia-dependent induction of
      gammaH2AX phosphorylation, DNA cross-linking, and cell-cycle arrest. We used
      Chinese hamster ovary cell-based DNA repair mutant cell lines and established
      that lines deficient in homology-dependent repair, but not lines deficient in
      base excision, nucleotide excision, or nonhomologous end-joining repair,
      exhibited marked sensitivity to TH-302 under hypoxia. Consistent with this
      finding, enhanced sensitivity to TH-302 was also observed in lines deficient in
      BRCA1, BRCA2, and FANCA. Finally, we characterized TH-302 activity in the three
      dimensional tumor spheroid and multicellular layer models. TH-302 showed much
      enhanced potency in H460 spheroids compared with H460 monolayer cells under
      normoxia. Multicellular layers composed of mixtures of parental HCT116 cells and
      HCT116 cells engineered to express an oxygen-insensitive bacterial nitroreductase
      showed that TH-302 exhibits a significant bystander effect.

PMID- 22147749
TI  - Trends and inequalities in late-life health and functioning in England.
AB  - BACKGROUND: Recently, late-life disability rates have declined in several
      countries of the Organisation for Economic Co-operation, but no national-level
      trend analysis for England has been available. The authors provide such analysis,
      including measures both early and late in the disablement process, and the
      authors investigate the extent to which temporal trends are associated with
      population changes in socioeconomic position (SEP). METHODS: The authors fit
      logistic models of trends in self-reports and nurse measures of 16 health
      indicators, based on cross-sectional data from those aged 65 years and older from
      the 1992 to 2007 Health Survey for England. RESULTS: Overall, prevalence rates of
      limitations in seeing, hearing and usual activities declined (p<0.05); ever
      smoking, measured high blood pressure, high cholesterol, and high C reactive
      protein decreased (p<0.05); and the proportion with limitations in self-care
      activities remained stable. But obesity and limitations in walking 200 yards and
      climbing stairs increased (p<0.05). Increases over time in education and non
      manual social class membership were associated with declines in smoking, C
      reactive protein and problems with usual activities. Had the changes in SEP not
      occurred, the increases in problems walking and climbing would have been greater.
      People with less education or of manual social classes experienced relatively
      worse trends for hearing, mobility functions and usual activities. The opposite
      was true for seeing. CONCLUSIONS: Recent trends in late-life health and
      functioning in England have been mixed. A better understanding of which specific
      activities pose challenges, how the environment in which activities are conducted
      influences functioning and the causes of relatively worse trends for some SEP
      groups is needed.

PMID- 22147750
TI  - Selection bias and patterns of confounding in cohort studies: the case of the
      NINFEA web-based birth cohort.
AB  - BACKGROUND: Several studies have examined the effects of sample selection on the
      exposure-outcome association estimates in cohort studies, but the reasons why
      this selection may induce bias have not been fully explored. AIMS: To investigate
      how sample selection of the web-based NINFEA birth cohort may change the
      confounding patterns present in the source population. METHODS: The
      characteristics of the NINFEA participants (n=1105) were compared with those of
      the wider source population-the Piedmont Birth Registry (PBR)-(n=36 092), and the
      association of two exposures (parity and educational level) with two outcomes
      (low birth weight and birth by caesarean section), while controlling for other
      risk factors, was studied. Specifically the associations among measured risk
      factors within each dataset were examined and the exposure-outcome estimates
      compared in terms of relative ORs. RESULTS: The associations of educational level
      with the other risk factors (alcohol consumption, folic acid intake, maternal
      age, pregnancy weight gain, previous miscarriages) partly differed between PBR
      and NINFEA. This was not observed for parity. Overall, the exposure-outcome
      estimates derived from NINFEA only differed moderately from those obtained in
      PBR, with relative ORs ranging between 0.74 and 1.03. CONCLUSIONS: Sample
      selection in cohort studies may alter the confounding patterns originally present
      in the general population. However, this does not necessarily introduce selection
      bias in the exposure-outcome estimates, as sample selection may reduce some of
      the residual confounding present in the general population.

PMID- 22147751
TI  - Migrating husbands and changing cardiovascular risk factors in the wife: a cross
      sectional study in Asian Indian women.
AB  - OBJECTIVE: The authors studied the influence of migration of husband on
      cardiovascular risk factors in Asian Indian women. METHODS: Population-based
      studies in women aged 35-70 years were performed in four urban and five rural
      locations. 4608 (rural 2604 and urban 2004) of the targeted 8000 (57%) were
      enrolled. Demographic details, lifestyle factors, anthropometry, fasting glucose
      and cholesterol were measured. Multivariate logistic and quadratic regression was
      performed to compare influence of migration and its duration on prevalence of
      risk factors. RESULTS: Details of migration were available in 4573 women (rural
      2267, rural-urban migrants 455, urban 1552 and urban-rural migrants 299).
      Majority were married, and illiteracy was high. Median (interquartile) duration
      of residence in urban locations among rural-urban migrants was 9 (4-18) years and
      in rural areas for urban-rural migrants 23 (18-30) years. In rural, rural-urban
      migrants, urban and urban-rural migrants, age-adjusted prevalence (%) of risk
      factors was tobacco use 41.9, 22.7, 18.8 and 38.1; sedentary lifestyle 69.7,
      82.0, 79.9 and 74.6; high-fat diet 33.3, 54.2, 66.1 and 61.1; overweight 21.3,
      42.7, 46.3 and 29.7; large waist 8.5, 38.5, 29.2 and 29.2; hypertension 30.4,
      49.4, 47.7 and 38.4; hypercholesterolaemia 14.4, 31.3, 26.6 and 9.1 and diabetes
      3.9, 15.8, 14.9 and 8.4, respectively (p<0.001). In rural-urban migrants, there
      was a significant correlation of duration of migration with waist size, waist-to
      hip ratio and systolic blood pressure (quadratic regression, p<0.001).
      Association of risk factors with migration remained significant, though
      attenuated, after adjustment for socioeconomic, lifestyle and obesity variables
      (logistic regression, p<0.01). CONCLUSIONS: Compared with rural women, rural
      urban migrants and urban have significantly greater cardiometabolic risk factors.
      Prevalence is lower in urban-rural migrants. There is significant correlation of
      duration of migration with obesity and blood pressure. Differences are attenuated
      after adjusting for social and lifestyle variables.

PMID- 22147752
TI  - Covalent modification of a volatile anesthetic regulatory site activates TASK-3
      (KCNK9) tandem-pore potassium channels.
AB  - TASK-3 (KCNK9) tandem-pore potassium channels provide a volatile anesthetic
      activated and Galpha(q) protein- and acidic pH-inhibited potassium conductance
      important in neuronal excitability. Met-159 of TASK-3 is essential for anesthetic
      activation and may contribute to the TASK-3 anesthetic binding site(s). We
      hypothesized that covalent occupancy of an anesthetic binding site would
      irreversibly activate TASK-3. We introduced a cysteine at residue 159 (M159C) and
      studied the rate and effect of Cys-159 modification by N-ethylmaleimide (NEM), a
      cysteine-selective alkylating agent. TASK-3 channels were transiently expressed
      in Fischer rat thyroid cells, and their function was studied in an Ussing
      chamber. NEM irreversibly activated M159C TASK-3, with minimal effects on wild
      type TASK-3. NEM-modified M159C channels were resistant to inhibition by both
      acidic pH and active Galpha(q) protein. M159C channels that were first inhibited
      by Galpha(q) protein were more-slowly activated by NEM, which suggests protection
      of Cys-159, and similar results were observed with isoflurane activation of wild
      type TASK-3. M159W and M159F TASK-3 mutants behaved like NEM-modified M159C
      channels, with increased basal currents and resistance to inhibition by active
      Galpha(q) protein or acidic pH. TASK-3 wild-type/M159C dimers expressed as a
      single polypeptide demonstrated that modification of a single Cys-159 was
      sufficient for TASK-3 activation, and M159F/M159C and M159W/M159C dimers provided
      evidence for cross-talk between subunits. The data are consistent with residue
      159 contributing to an anesthetic regulatory site or sites, and they suggest that
      volatile anesthetics, through perturbations at a single site, increase TASK-3
      channel activity and disrupt its regulation by active Galpha(q) protein, a
      determinant of central nervous system arousal and consciousness.

PMID- 22147753
TI  - Antitumor indolequinones induced apoptosis in human pancreatic cancer cells via
      inhibition of thioredoxin reductase and activation of redox signaling.
AB  - Indolequinones (IQs) were developed as potential antitumor agents against human
      pancreatic cancer. IQs exhibited potent antitumor activity against the human
      pancreatic cancer cell line MIA PaCa-2 with growth inhibitory IC(50) values in
      the low nanomolar range. IQs were found to induce time- and concentration
      dependent apoptosis and to be potent inhibitors of thioredoxin reductase 1 (TR1)
      in MIA PaCa-2 cells at concentrations equivalent to those inducing growth
      inhibitory effects. The mechanism of inhibition of TR1 by the IQs was studied in
      detail in cell-free systems using purified enzyme. The C-terminal selenocysteine
      of TR1 was characterized as the primary adduction site of the IQ-derived reactive
      iminium using liquid chromatography-tandem mass spectrometry analysis. Inhibition
      of TR1 by IQs in MIA PaCa-2 cells resulted in a shift of thioredoxin-1 redox
      state to the oxidized form and activation of the p38/c-Jun NH(2)-terminal kinase
      (JNK) mitogen-activated protein kinase (MAPK) signaling pathway. Oxidized
      thioredoxin is known to activate apoptosis signal-regulating kinase 1, an
      upstream activator of p38/JNK in the MAPK signaling cascade and this was
      confirmed in our study providing a potential mechanism for IQ-induced apoptosis.
      These data describe the redox and signaling events involved in the mechanism of
      growth inhibition induced by novel inhibitors of TR1 in human pancreatic cancer
      cells.

PMID- 22147754
TI  - Genetic analysis of an interspecific cross in ornamental Viburnum (Viburnum).
AB  - A genetic analysis was performed on a population derived from crosses between
      Viburnum lantana and Viburnum carlesii. Linkage maps were developed for each
      species using AFLP, random amplified polymorphic DNA (RAPD), and sequence-tagged
      site markers and a half-sib approach that took advantage of both the polymorphism
      between the species and the heterozygosity within each parent. The map for V.
      lantana consisted of 153 DNA markers and spanned approximately 750 cM, whereas
      that for V. carlesii contained 133 markers and covered 700 cM. These maps were
      used to determine the location of several major genes influencing leaf spot
      resistance, Verticillium wilt resistance, bud color, and flower scent. Both
      species contained moderate levels of heterozygosity. Flow cytometric analysis
      revealed that the genome of V. lantana was 40% larger than that of V. carlesii,
      and this difference was paralleled by a proportionally greater number of
      intercross markers (markers segregating 3:1) from V. lantana than from V.
      carlesii. In addition, V. lantana (n = 9) displayed a 10th linkage group for
      which no homolog in V. carlesii (n = 9) could be found and which contained only
      markers present in the former species and absent in the latter. These results
      suggest that Viburnum could be an interesting genetic model for Caprifoliaceae
      sensu lato.

PMID- 22147755
TI  - Identification of quantitative trait Loci for lipid metabolism in rice seeds.
AB  - Plant seed oil is important for human dietary consumption and industrial
      application. The oil trait is controlled by quantitative trait loci (QTLs), but
      no QTLs for fatty acid composition are known in rice, the monocot model plant.
      QTL analysis was performed using F(2) and F(2:3) progeny from a cross of an
      indica variety and a japonica variety. Gas chromatography-mass spectrometry (GC
      MS) analysis revealed significant differences between parental lines in fatty
      acid composition of brown rice oil, and 29 associated QTLs in F(2) and/or F(2:3)
      populations were identified throughout the rice genome, except chromosomes 9 and
      10. Eight QTLs were repeatedly identified in both populations across different
      environments. Five loci pleiotropically controlled different traits, contributing
      to complex interactions of oil with fatty acids and between fatty acids. Nine
      rice orthologs of Arabidopsis genes encoding key enzymes in lipid metabolism co
      localized with 11 mapped QTLs. A strong QTL for oleic (18:1) and linoleic (18:2)
      acid were associated with a rice ortholog of a gene encoding acyl
      CoA:diacylglycerol acyltransferase (DGAT), and another for palmitic acid (16:0)
      mapped similarly to the acyl-ACP thioesterase (FatB) gene ortholog. Our approach
      rapidly and efficiently identified candidate genes for mapped QTLs controlling
      fatty acid composition and oil concentration, providing information for improving
      rice grain quality by marker assisted selection.

PMID- 22147756
TI  - Altered lignin biosynthesis improves cellulosic bioethanol production in
      transgenic maize plants down-regulated for cinnamyl alcohol dehydrogenase.
AB  - Cinnamyl alcohol dehydrogenase (CAD) is a key enzyme involved in the last step of
      monolignol biosynthesis. The effect of CAD down-regulation on lignin production
      was investigated through a transgenic approach in maize. Transgenic CAD-RNAi
      plants show a different degree of enzymatic reduction depending on the analyzed
      tissue and show alterations in cell wall composition. Cell walls of CAD-RNAi
      stems contain a lignin polymer with a slight reduction in the S-to-G ratio
      without affecting the total lignin content. In addition, these cell walls
      accumulate higher levels of cellulose and arabinoxylans. In contrast, cell walls
      of CAD-RNAi midribs present a reduction in the total lignin content and of cell
      wall polysaccharides. In vitro degradability assays showed that, although to a
      different extent, the changes induced by the repression of CAD activity produced
      midribs and stems more degradable than wild-type plants. CAD-RNAi plants grown in
      the field presented a wild-type phenotype and produced higher amounts of dry
      biomass. Cellulosic bioethanol assays revealed that CAD-RNAi biomass produced
      higher levels of ethanol compared to wild-type, making CAD a good target to
      improve both the nutritional and energetic values of maize lignocellulosic
      biomass.

PMID- 22147757
TI  - Medical home access and health care use and expenditures among children with
      special health care needs.
AB  - OBJECTIVE: To test associations between having a medical home and health services
      use and expenditures among US children with special health care needs (CSHCN).
      DESIGN: Cross-sectional analysis. SETTING: The 2003-2008 Medical Expenditure
      Panel Surveys. PARTICIPANTS: A total of 9816 CSHCN up to 17 years, including 1056
      with a functional or sensory limitation and 8760 without a limitation. MAIN
      EXPOSURE: Parent or caregiver report of CSHCN having a medical home. MAIN OUTCOME
      MEASURES: We examined CSHCN's annual use of outpatient, inpatient, emergency
      department, and dental visits, and annual outpatient, inpatient, emergency
      department, prescription medication, dental, and other health care expenditures.
      RESULTS: CSHCN with a medical home had 14% more dental visits compared with CSHCN
      without a medical home (incidence rate ratio [IRR], 1.14; 95% CI, 1.03-1.25);
      this finding is significant for CSHCN without limitations but not for those with
      limitations. The medical home was associated with greater odds of incurring
      total, outpatient, prescription medication, and dental expenditures (odds ratio
      range, 1.25-1.92). Among CSHCN with a limitation, children with a medical home
      had lower annual inpatient expenditures compared with those without a medical
      home (mean, -$968; 95% CI, -$121 to -$1928), and among CSHCN without a
      limitation, children with a medical home had higher annual prescription
      medication expenditures compared with those without a medical home (mean, $87;
      95% CI, $22-$153). CONCLUSIONS: There were few differences in annual health
      services use and expenditures between CSHCN with and without a medical home.
      However, the medical home may be associated with lower inpatient expenditures and
      higher prescription medication expenditures within subgroups of CSHCN.

PMID- 22147758
TI  - Parental recall of doctor communication of weight status: national trends from
      1999 through 2008.
AB  - OBJECTIVE: To examine time trends in parental reports of health professional
      notification of childhood overweight over the last decade and to determine the
      characteristics most associated with such notification. DESIGN: Secondary data
      analysis using chi(2) tests to examine the relationships between multiple factors
      on the reports of parents and/or caregivers (hereinafter "parents") and logistic
      regression for multivariate analysis. SETTING: National Health and Nutrition
      Examination Survey, 1999 through 2008. PARTICIPANTS: Parents of 4985 children
      aged 2 to 15 years with body mass index (BMI) in the 85th percentile or higher
      based on measured height and weight. MAIN OUTCOME MEASURES: Affirmative answer to
      the following question: "Has a doctor or health professional ever told you that
      your child is overweight?" RESULTS: During 1999 through 2008, 22% of parents of
      children with BMIs in the 85th percentile or higher reported having been told by
      a doctor or health professional that their child was overweight; recall of
      notification was actually more likely among nonwhite and poor children. This
      percentage increased from 19.4% to 23.2% from the 1999-2004 period and further
      accelerated in the 2007-2008 period to 29.1%. The time trend persisted in
      multivariate analyses, with significantly more parents reporting having been told
      in 2007 through 2008 than in 1999 through 2000. CONCLUSION: Fewer than one
      quarter of parents of overweight children report having been told that their
      child was overweight. While reports of notification have increased over the last
      decade (perhaps because of [1] revised definitions of overweight and obesity, [2]
      increased concern about children with BMIs in the 85th to 95th sex- and age
      specific percentiles, or [3] improved recall by parents), further research is
      necessary to determine where and why communication of weight status breaks down.

PMID- 22147759
TI  - Can we ensure that children with public insurance have access to necessary, high
      quality pediatric specialty care?

PMID- 22147760
TI  - Academic medical centers and equity in specialty care access for children.
AB  - OBJECTIVE: To test whether specialty clinics' academic medical center (AMC)
      affiliation was associated with equity in scheduling appointments for children
      with public vs private insurance. Academic medical centers are safety-net
      providers of specialty medical care and it is unknown whether equitable access is
      afforded by AMCs across insurance conditions. DESIGN: Audit study data were
      linked to data describing audited clinics. SETTING: Specialty clinics serving
      children residing in Cook County, Illinois. PARTICIPANTS: From January-May 2010,
      273 clinics were each called twice. MAIN OUTCOME MEASURES: Logistic regression
      was used to examine associations between AMC affiliation and discriminatory
      denials of Medicaid-Children's Health Insurance Program (CHIP) (ie, nonacceptance
      of Medicaid-CHIP when accepting commercial insurance), controlling for clinics'
      specialty type, practice size, neighborhood poverty level, and physicians'
      credentials. Among clinics that accepted both insurances, linear regression was
      used to examine the association between wait times (days) for appointments and
      insurance status, adjusting for covariates. Tests for interaction terms were
      performed to identify changes in wait time for academic clinics across insurance
      status. RESULTS: Of the 273 paired calls to clinics, 155 (57%) resulted in
      discriminatory denials of Medicaid-CHIP. The odds of a discriminatory denial were
      45% lower if a clinic was AMC affiliated (odds ratio, 0.55; 95% CI, 0.31-0.99).
      On average, academic clinics scheduled Medicaid-CHIP appointments with wait times
      40 days longer than private insurance (beta, 40.73; 95% CI, 5.06-76.41).
      CONCLUSIONS: Affiliation with an AMC was associated with fewer discriminatory
      denials of children with Medicaid-CHIP. However, children with Medicaid-CHIP had
      significantly longer wait times at AMC-affiliated clinics compared with privately
      insured children. Academic medical centers' propensity toward serving publicly
      insured patients makes them candidates for targeted resource allocation, perhaps
      with incentives contingent on equitable appointment acceptance and wait times.

PMID- 22147761
TI  - Promoting the health of our youth: why physical activity policies are critical.

PMID- 22147763
TI  - The impact of state laws and district policies on physical education and recess
      practices in a nationally representative sample of US public elementary schools.
AB  - OBJECTIVE: To examine the impact of state- and school district-level policies on
      the prevalence of physical education (PE) and recess in a nationally
      representative sample of US public elementary schools. DESIGN: Analyses from
      annual, nationally representative, cross-sectional surveys of school
      administrators in the United States. SETTING: Data were collected through surveys
      conducted between February and June during the 2006-2007 through 2008-2009 school
      years. State laws and district policies were compiled annually by researchers at
      the University of Illinois at Chicago using established legal research
      techniques. PARTICIPANTS: The sample size was 47 states, 690 districts, and 1761
      schools. MAIN EXPOSURES: State- and school district-level PE and recess-related
      laws. MAIN OUTCOME MEASURES: Twenty minutes of daily recess and 150 min/wk of PE.
      RESULTS: The odds of schools having 150 min/wk of PE increased if they were
      located in states (odds ratio [OR], 2.8; 95% CI, 1.3-5.7) or school districts
      (OR, 2.4; 95% CI, 1.3-4.3) having a law or policy requiring 150 min/wk of PE.
      Schools located in states with laws encouraging daily recess were significantly
      more likely to have 20 minutes of recess daily (OR, 1.8; 95% CI, 1.2-2.8).
      District policies were not significantly associated with school-level recess
      practices. Adequate PE time was inversely associated with recess and vice versa,
      suggesting that schools are substituting one form of physical activity for
      another rather than providing the recommended amount of both recess and PE.
      CONCLUSION: By mandating PE or recess, policy makers can effectively increase
      school-based physical activity opportunities for youth.

PMID- 22147762
TI  - Prevalence of clinically important traumatic brain injuries in children with
      minor blunt head trauma and isolated severe injury mechanisms.
AB  - OBJECTIVE: To determine the prevalence of clinically important traumatic brain
      injuries (TBIs) with severe injury mechanisms in children with minor blunt head
      trauma but with no other risk factors from the Pediatric Emergency Care Applied
      Research Network (PECARN) TBI prediction rules (defined as isolated severe injury
      mechanisms). DESIGN: Secondary analysis of a large prospective observational
      cohort study. SETTING: Twenty-five emergency departments participating in the
      PECARN. PATIENTS: Children with minor blunt head trauma and Glasgow Coma Scale
      scores of at least 14. INTERVENTION: Treating clinicians completed a structured
      data form that included injury mechanism (severity categories defined a priori).
      MAIN OUTCOME MEASURES: Clinically important TBIs were defined as intracranial
      injuries resulting in death, neurosurgical intervention, intubation for more than
      24 hours, or hospital admission for at least 2 nights. We investigated the rate
      of clinically important TBIs in children with either severe injury mechanisms or
      isolated severe injury mechanisms. RESULTS: Of the 42,412 patients enrolled in
      the overall study, 42,099 (99%) had injury mechanisms recorded, and their data
      were included for analysis. Of all study patients, 5869 (14%) had severe injury
      mechanisms, and 3302 (8%) had isolated severe injury mechanisms. Overall, 367
      children had clinically important TBIs (0.9%; 95% CI, 0.8%-1.0%). Of the 1327
      children younger than 2 years with isolated severe injury mechanisms, 4 (0.3%;
      95% CI, 0.1%-0.8%) had clinically important TBIs, as did 12 of the 1975 children
      2 years or older (0.6%; 95% CI, 0.3%-1.1%). CONCLUSION: Children with isolated
      severe injury mechanisms are at low risk of clinically important TBI, and many do
      not require emergent neuroimaging.

PMID- 22147764
TI  - The Syrian hamster embryo (SHE) assay (pH 6.7): mechanisms of cell transformation
      and application of vibrational spectroscopy to objectively score endpoint
      alterations.
AB  - Using morphological transformation as an endpoint, the Syrian hamster embryo
      (SHE) cell transformation assay (pH 6.7) is an in vitro system with a high
      sensitivity and specificity for testing the carcinogenic potential of test
      agents. Advantages of the assay are that SHE cells are metabolically competent,
      genetically stable and acquire spontaneous transformation with a low frequency;
      additionally, it detects both genotoxic and non-genotoxic carcinogens. However,
      in comparison with other short-term mammalian cell assays, it is time consuming,
      laborious and, most importantly, the visual scoring of morphological
      transformation might be subjective. In this review, we examine the background to
      the test and why it has the potential for use in safety risk assessment.
      Additionally, we propose a novel approach to objectively interrogate and classify
      SHE colonies using vibrational spectroscopy coupled to a mathematical framework
      for high-throughput screening. It is our view that this alternative approach has
      the potential to improve the sensitivity and specificity of the in vitro SHE
      assay.

PMID- 22147765
TI  - Histamine H4 receptor optimizes T regulatory cell frequency and facilitates anti
      inflammatory responses within the central nervous system.
AB  - Histamine is a biogenic amine that mediates multiple physiological processes,
      including immunomodulatory effects in allergic and inflammatory reactions, and
      also plays a key regulatory role in experimental allergic encephalomyelitis, the
      autoimmune model of multiple sclerosis. The pleiotropic effects of histamine are
      mediated by four G protein-coupled receptors, as follows: Hrh1/H(1)R, Hrh2/H(2)R,
      Hrh3/H(3)R, and Hrh4/H(4)R. H(4)R expression is primarily restricted to
      hematopoietic cells, and its role in autoimmune inflammatory demyelinating
      disease of the CNS has not been studied. In this study, we show that, compared
      with wild-type mice, animals with a disrupted Hrh4 (H(4)RKO) develop more severe
      myelin oligodendrocyte glycoprotein (MOG)(35?x{2013}55)-induced experimental
      allergic encephalomyelitis. Mechanistically, we also show that H(4)R plays a role
      in determining the frequency of T regulatory (T(R)) cells in secondary lymphoid
      tissues, and regulates T(R) cell chemotaxis and suppressor activity. Moreover,
      the lack of H(4)R leads to an impairment of an anti-inflammatory response due to
      fewer T(R) cells in the CNS during the acute phase of the disease and an increase
      in the proportion of Th17 cells.

PMID- 22147766
TI  - New insights on OX40 in the control of T cell immunity and immune tolerance in
      vivo.
AB  - OX40 is a T cell costimulatory molecule that belongs to the TNFR superfamily. In
      the absence of immune activation, OX40 is selectively expressed by Foxp3(+)
      regulatory T cells (Tregs), but not by resting conventional T cells. The exact
      role of OX40 in Treg homeostasis and function remains incompletely defined. In
      this study, we demonstrate that OX40 engagement in vivo in naive mice induces
      initial expansion of Foxp3(+) Tregs, but the expanded Tregs have poor suppressive
      function and exhibit features of exhaustion. We also show that OX40 enables the
      activation of the Akt and Stat5 pathways in Tregs, resulting in transient
      proliferation of Tregs and reduced levels of Foxp3 expression. This creates a
      state of relative IL-2 deficiency in naive mice that further impacts Tregs. This
      exhausted Treg phenotype can be prevented by exogenous IL-2, as both OX40 and IL
      2 agonists drive further expansion of Tregs in vivo. Importantly, Tregs expanded
      by both OX40 and IL-2 agonists are potent suppressor cells, and in a heart
      transplant model, they promote long-term allograft survival. Our data reveal a
      novel role for OX40 in promoting immune tolerance and may have important clinical
      implications.

PMID- 22147767
TI  - Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene
      induction by lupus immune complexes.
AB  - Immune complexes (ICs) play a pivotal role in causing inflammation in systemic
      lupus erythematosus (SLE). Yet, it remains unclear what the dominant blood cell
      type(s) and inflammation-related gene programs stimulated by lupus ICs are. To
      address these questions, we exposed normal human PBMCs or CD14(+) isolated
      monocytes to SLE ICs in the presence or absence of C1q and performed microarray
      analysis and other tests for cell activation. By microarray analysis, we
      identified genes and pathways regulated by SLE ICs that are both type I IFN
      dependent and independent. We also found that C1q-containing ICs markedly reduced
      expression of the majority of IFN-response genes and also influenced the
      expression of multiple other genes induced by SLE ICs. Surprisingly, IC
      activation of isolated CD14(+) monocytes did not upregulate CD40 and CD86 and
      only modestly stimulated inflammatory gene expression. However, when monocyte
      subsets were purified and analyzed separately, the low-abundance CD14(dim)
      ("patrolling") subpopulation was more responsive to ICs. These observations
      demonstrate the importance of plasmacytoid dendritic cells, CD14(dim) monocytes,
      and C1q as key regulators of inflammatory properties of ICs and identify many
      pathways through which they act.

PMID- 22147769
TI  - The Notch signaling pathway in hematopoiesis and hematologic malignancies.

PMID- 22147768
TI  - Microbial infection-induced expansion of effector T cells overcomes the
      suppressive effects of regulatory T cells via an IL-2 deprivation mechanism.
AB  - Foxp3(+) regulatory T (Treg) cells are a critical cell population that suppresses
      T cell activation in response to microbial and viral pathogens. We identify a
      cell-intrinsic mechanism by which effector CD4(+) T cells overcome the
      suppressive effects of Treg cells in the context of three distinct infections:
      Toxoplasma gondii, Listeria monocytogenes, and vaccinia virus. The acute
      responses to the parasitic, bacterial, and viral pathogens resulted in a
      transient reduction in frequency and absolute number of Treg cells. The infection
      induced partial loss of Treg cells was essential for the initiation of potent Th1
      responses and host protection against the pathogens. The observed disappearance
      of Treg cells was a result of insufficiency in IL-2 caused by the expansion of
      pathogen-specific CD4(+) T cells with a limited capacity of IL-2 production.
      Exogenous IL-2 treatment during the parasitic, bacterial, and viral infections
      completely prevented the loss of Treg cells, but restoration of Treg cells
      resulted in a greatly enhanced susceptibility to the pathogens. These results
      demonstrate that the transient reduction in Treg cells induced by pathogens via
      IL-2 deprivation is essential for optimal T cell responses and host resistance to
      microbial and viral pathogens.

PMID- 22147770
TI  - Chronic myeloid leukemia: the basis of treatment for tomorrow.

PMID- 22147773
TI  - Classics in pediatrics: a 100-year history of pediatrics in the United States.

PMID- 22147771
TI  - Immune thrombocytopenia in children and adults: what's the same, what's
      different?

PMID- 22147774
TI  - The next century of children's health care: addressing disparities, workforce
      deficiencies, and undercoordinated services.

PMID- 22147776
TI  - Improving detection of adolescent hearing loss.
AB  - OBJECTIVES: To compare a protocol for pure-tone threshold testing, capable of
      detecting high-frequency hearing loss as indicated by notched audiometric
      configurations, with the current school rapid hearing screen and to determine
      typical adolescent noise exposures associated with notched audiometric
      configurations. DESIGN: In conjunction with required school rapid hearing
      screening, a pure-tone threshold testing protocol was administered, specifically
      to test hearing at high frequencies. A single audiologist reviewed the results.
      Students completed a survey assessing their noise exposures. SETTING: A public
      high school in Pennsylvania. PARTICIPANTS: Eleventh-grade students. MAIN OUTCOME
      MEASURE: Notched audiometric configurations on the pure-tone threshold test.
      RESULTS: Among 296 participants, 78 (26.4%) failed pure-tone threshold testing
      compared with 15 (5.1%) failing rapid hearing screening. Among those failing the
      pure-tone threshold testing, 67 (85.9%) failed due to notched audiometric
      configurations. Self-reported headphone use with an MP3 player was significantly
      associated with notched audiometric configurations compared with use of earbuds
      or stereo connection/docking systems. CONCLUSIONS: Pure-tone threshold testing
      incorporating high frequencies detects adolescent hearing loss more often than
      rapid hearing screens. Most state hearing screens omit high-frequency testing,
      potentially missing high-frequency losses, such as noise-induced hearing loss.
      Because noise-induced hearing loss in particular is preventable and hazardous
      noise exposures have increased, a reliable school hearing screen to detect high
      frequency hearing loss in adolescents is warranted.

PMID- 22147777
TI  - Dating violence among adolescents presenting to a pediatric emergency department.
AB  - OBJECTIVES: To determine the prevalence and characteristics of dating violence
      experienced by adolescents seeking care in a pediatric emergency department and
      how often adolescents reporting victimization follow up with suggested resources.
      DESIGN: Cross-sectional survey. SETTING: An urban pediatric emergency department.
      PARTICIPANTS: Of 327 participants, 235 (71.9%) were female and 92 (28.1%) were
      male, with a mean (SE) age of 18.7 (0.10) years. INTERVENTIONS: Adolescents aged
      13 to 21 years completed a survey including demographic characteristics and a
      validated measure of dating violence. Those reporting victimization received
      information about local resources and were contacted 1 month later by telephone
      to determine their use of local resources. MAIN OUTCOME MEASURES: Dating violence
      exposure and subsequent use of resources. RESULTS: Among the adolescents, 54.8%
      reported physical and/or sexual victimization (54.0% of girls vs 56.7% of boys;
      odds ratio = 0.9; 95% CI, 0.6-1.5), and 59.4% reported perpetration of physical
      and/or sexual violence (62.1% of girls vs 52.3% of boys; odds ratio = 1.4; 95%
      CI, 0.9-2.4). Girls were more likely than boys to perpetrate physical violence
      (52.2% vs 36.1%, respectively; odds ratio = 1.9; 95% CI, 1.2-3.2) but were also
      more than 5 times as likely to report fear of sustaining serious injury from a
      partner (16.2% vs 3.1%, respectively; odds ratio = 6.0; 95% CI, 1.4- 26.2). Young
      age, more intimate partners, and a history of a recent physical fight were
      independently associated with both dating violence victimization and
      perpetration. Only 4 of the 127 participants with follow-up interviews (3.1%)
      used any resources provided. CONCLUSION: Dating violence perpetration and
      victimization rates for both boys and girls who had at least 1 dating
      relationship are high in this pediatric emergency department population.

PMID- 22147775
TI  - Corticostriatal-limbic gray matter morphology in adolescents with self-reported
      exposure to childhood maltreatment.
AB  - OBJECTIVE: To study the relationship between self-reported exposure to childhood
      maltreatment (CM) and cerebral gray matter (GM) morphology in adolescents without
      psychiatric diagnoses. DESIGN: Associations were examined between regional GM
      morphology and exposure to CM (measured using a childhood trauma self-report
      questionnaire for physical, emotional, and sexual abuse and for physical and
      emotional neglect). SETTING: University hospital. PARTICIPANTS: Forty-two
      adolescents without psychiatric diagnoses. MAIN OUTCOME MEASURES: Correlations
      between childhood trauma self-report questionnaire scores and regional GM volume
      were assessed in voxel-based analyses of structural magnetic resonance images.
      Relationships among GM volume, subtypes of exposure to CM, and sex were explored.
      RESULTS: Childhood trauma self-report questionnaire total scores correlated
      negatively (P < .005) with GM volume in prefrontal cortex, striatum, amygdala,
      sensory association cortices, and cerebellum. Physical abuse, physical neglect,
      and emotional neglect were associated with rostral prefrontal reductions.
      Decreases in dorsolateral and orbitofrontal cortices, insula, and ventral
      striatum were associated with physical abuse. Decreases in cerebellum were
      associated with physical neglect. Decreases in dorsolateral, orbitofrontal, and
      subgenual prefrontal cortices, striatum, amygdala, hippocampus, and cerebellum
      were associated with emotional neglect. Decreases in the latter emotion
      regulation regions were also associated with childhood trauma self-report
      questionnaire scores in girls, while caudate reductions (which may relate to
      impulse dyscontrol) were seen in boys. CONCLUSIONS: Exposure to CM was associated
      with corticostriatal-limbic GM reductions in adolescents. Even if adolescents
      reporting exposure to CM do not present with symptoms that meet full criteria for
      psychiatric disorders, they may have corticostriatal-limbic GM morphologic
      alterations that place them at risk for behavioral difficulties. Vulnerabilities
      may be moderated by sex and by subtypes of exposure to CM.

PMID- 22147778
TI  - Helium-oxygen therapy for infants with bronchiolitis: a randomized controlled
      trial.
AB  - OBJECTIVE: To compare nebulized racemic epinephrine delivered by 70% helium and
      30% oxygen or 100% oxygen followed by helium-oxygen inhalation therapy via high
      flow nasal cannula (HFNC) vs oxygen inhalation via HFNC in the treatment of
      bronchiolitis. DESIGN: Prospective, randomized, controlled, single-blind trial.
      SETTING: This study was conducted from October 1, 2004, through May 31, 2008, in
      the emergency department of an urban, tertiary care children's hospital. Patients
      Infants aged 2 to 12 months with a Modified Wood's Clinical Asthma Score (M-WCAS)
      of 3 or higher. INTERVENTIONS: Patients initially received nebulized albuterol
      treatment driven by 100% oxygen. Patients were randomized to the helium-oxygen or
      oxygen group and received nebulized racemic epinephrine via a face mask. After
      nebulization, humidified helium-oxygen or oxygen was delivered by HFNC. After 60
      minutes of inhalation therapy, patients with an M-WCAS of 2 or higher received a
      second delivery of nebulized racemic epinephrine followed by helium-oxygen or
      oxygen delivered by HFNC. Main Outcome Measure Degree of improvement of M-WCAS
      for 240 minutes or until emergency department discharge. RESULTS: Of 69 infants
      enrolled, 34 were randomized to the helium-oxygen group and 35 to the oxygen
      group. The mean change in M-WCAS from baseline to 240 minutes or emergency
      department discharge was 1.84 for the helium-oxygen group compared with 0.31 for
      the oxygen group (P < .001). The mean M-WCAS was significantly improved for the
      helium-oxygen group compared with the oxygen group at 60 minutes (P = .005), 120
      minutes (P < .001), 180 minutes (P < .001), and 240 minutes (P < .001).
      CONCLUSION: Nebulized racemic epinephrine delivered by helium-oxygen followed by
      helium-oxygen inhalation therapy delivered by HFNC was associated with a greater
      degree of clinical improvement compared with that delivered by oxygen among
      infants with bronchiolitis. Trial Registration clinicaltrials.gov Identifier:
      NCT00116584.

PMID- 22147779
TI  - Association of vascular endothelial growth factor +936 C/T single-nucleotide
      polymorphism with pregnancies complicated by small-for-gestational-age babies.
AB  - OBJECTIVES: To examine whether single-nucleotide polymorphisms (SNPs) in VEGFA (
      2578 C/A and +936 C/T) associate with small-for-gestational-age (SGA) pregnancies
      and to identify their effects on first-trimester placental VEGFA expression.
      DESIGN: Multicenter prospective cohort study. SETTINGS: Adelaide, Australia, and
      Auckland, New Zealand. PARTICIPANTS: A total of 3234 nulliparous pregnant women,
      their partners, and their infants. MAIN OUTCOME MEASURES: The SNPs in the parent
      infant trios and first-trimester placentae (n = 74) were genotyped. Placental
      VEGFA messenger RNA expression was determined by quantitative reverse
      transcription-polymerase chain reaction. Small for gestational age was defined as
      a birth weight less than the 10th customized birth weight percentile adjusted for
      maternal height, weight, parity, and ethnicity and for gestational age at
      delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20
      weeks' gestation, and resistance indices greater than the 90th percentile were
      considered abnormal. RESULTS: Of 2123 pregnancies, 1176 (55.4%) were
      uncomplicated and 216 (10.2%) had SGA infants. Neonatal VEGFA +936 C/T SNP
      associates with SGA (adjusted odds ratio [aOR], 1.6; 95% CI, 1.0-2.3), SGA with
      abnormal Doppler findings (aOR, 3.5; 95% CI, 1.8-7.1), lower birth weight (P =
      .006), customized birth weight percentile (P = .049), and abnormal uterine artery
      Doppler findings (OR, 2.5; 95% CI, 1.2-5.4). Maternal VEGFA +936 C/T associates
      with abnormal umbilical artery Doppler findings (OR, 1.5; 95% CI, 1.1-2.2). VEGFA
      +936 CT+TT first-trimester placentae have 36% lower VEGFA messenger RNA
      expression compared with CC (P = .045). CONCLUSION: Neonatal VEGFA +936 C/T
      associates with SGA, and the association is stronger for SGA with abnormal
      uterine or umbilical artery Doppler findings. The SNP also associates with
      reduced first-trimester placental VEGFA expression, suggesting that it may have a
      role in the pathogenesis of SGA. Trial Registration clinicaltrials.gov
      Identifier: ACTRN12607000551493.

PMID- 22147780
TI  - Picture of the month: anterior chamber cholesterolosis in Coats disease.

PMID- 22147782
TI  - School-based hearing screening won't prevent noise-induced hearing loss.

PMID- 22147781
TI  - Conceptual and methodological issues in neuroimaging studies of the effects of
      child maltreatment.

PMID- 22147783
TI  - Searching for effective treatment.

PMID- 22147784
TI  - Rapid response team implementation in a children's hospital.

PMID- 22147785
TI  - Preventing hearing loss among children and adolescents.

PMID- 22147788
TI  - No evidence of bias in trial showing BCG reduces neonatal mortality.

PMID- 22147786
TI  - Valacyclovir suppressive therapy reduces plasma and breast milk HIV-1 RNA levels
      during pregnancy and postpartum: a randomized trial.
AB  - BACKGROUND: The effect of herpes simplex virus type 2 (HSV-2) suppression on
      human immunodeficiency virus type 1 (HIV-1) RNA in the context of prevention of
      mother-to-child transmission (PMTCT) interventions is unknown. METHODS: Between
      April 2008 and August 2010, we conducted a randomized, double-blind trial of
      twice daily 500 mg valacyclovir or placebo beginning at 34 weeks gestation in 148
      HIV-1/HSV-2 coinfected pregnant Kenyan women ineligible for highly active
      antiretroviral therapy (CD4 > 250 cells/mm(3)). Women received zidovudine and
      single dose nevirapine for PMTCT and were followed until 12 months postpartum.
      RESULTS: Mean baseline plasma HIV-1 RNA was 3.88 log(10) copies/mL. Mean plasma
      HIV-1 was lower during pregnancy (-.56 log(10) copies/mL; 95% confidence interval
      [CI], -.77 to -.34) and after 6 weeks postpartum (-.51 log(10) copies/mL; 95% CI,
      -.73 to -.30) in the valacyclovir arm than the placebo arm. Valacyclovir reduced
      breast milk HIV-1 RNA detection at 6 and 14 weeks postpartum compared with
      placebo (30% lower, P = .04; 46% lower, P = .01, respectively), but not after 14
      weeks. Cervical HIV-1 RNA detection was similar between arms (P = .91).
      CONCLUSIONS: Valacyclovir significantly decreased early breast milk and plasma
      HIV-1 RNA among women receiving PMTCT. CLINICAL TRIALS REGISTRATION: NCT00530777.

PMID- 22147789
TI  - Non-specific effects of BCG?

PMID- 22147790
TI  - Immunization of mice with vibrio cholerae outer-membrane vesicles protects
      against hyperinfectious challenge and blocks transmission.
AB  - BACKGROUND: Vibrio cholerae excreted by cholera patients is "hyperinfectious"
      (HI), which can be modeled by passage through infant mice. Immunization of adult
      female mice with V. cholerae outer-membrane vesicles (OMVs) passively protects
      suckling mice from challenge. Although V. cholerae is unable to colonize
      protected pups, the bacteria survive passage and have the potential to be
      transmitted to susceptible individuals. Here, we investigated the impact of OMV
      immunization and the HI state on V. cholerae transmission. METHODS: Neonatal mice
      suckled by OMV- or sham-immunized dams were challenged with HI V. cholerae. The
      infectivity of spatially and temporally separate V. cholerae populations obtained
      from infected naive or protected pups was tested. Recombination-based in vivo
      expression technology was used to assess virulence gene expression within these
      populations. RESULTS: OMV immunization significantly reduced colonization of
      neonates challenged with HI V. cholerae. Vibrio cholerae that had colonized the
      naive host was HI, whereas V. cholerae excreted by neonates born to OMV-immunized
      dams, although viable, was hypoinfectious and failed to fully induce virulence
      gene expression. CONCLUSIONS: OMV immunization can significantly reduce the V.
      cholerae burden upon challenge with HI V. cholerae and can also block
      transmission from immune mice by reducing the infectivity of shed bacteria.

PMID- 22147791
TI  - GLA-SE, a synthetic toll-like receptor 4 agonist, enhances T-cell responses to
      influenza vaccine in older adults.
AB  - BACKGROUND: The decline in influenza vaccine efficacy in older adults is
      associated with a limited ability of current split-virus vaccines (SVVs) to
      stimulate cytotoxic T lymphocyte (CTL) responses required for clinical protection
      against influenza. METHODS: The Toll-like receptor 4 agonist glucopyranosyl lipid
      adjuvant-stable emulsion (GLA-SE) was combined with SVV to stimulate peripheral
      blood mononuclear cells (PBMCs) in vitro to determine the cytokine response in
      dendritic cell subsets. Stimulated PBMCs were then challenged with live influenza
      virus to mimic the response to natural infection following vaccination, using
      previously identified T-cell correlates of protection. RESULTS: GLA-SE
      significantly increased the proportion of myeloid dendritic cells that produced
      tumor necrosis factor alpha, interleukin 6, and interleukin 12. When combined
      with SVV to stimulate PBMCs in vitro, this effect of GLA-SE was shown to regulate
      a T-helper 1 cell response upon challenge with live influenza virus; interleukin
      10 production was suppressed, thus significantly increasing the interferon gamma
      to interleukin 10 ratio and the cytolytic (granzyme B) response to influenza
      virus challenge, both of which have been shown to correlate with protection
      against influenza in older adults. CONCLUSIONS: Our findings suggest that a novel
      adjuvant, GLA-SE, combined with standard SVV has the potential to significantly
      improve vaccine-mediated protection against influenza in older adults.

PMID- 22147792
TI  - Longitudinal analysis of carcinogenic human papillomavirus infection and
      associated cytologic abnormalities in the Guanacaste natural history study:
      looking ahead to cotesting.
AB  - BACKGROUND: Few studies have addressed the timing of cervical cytologic
      abnormalities and human papillomavirus (HPV) positivity during the course of an
      infection. It remains largely unknown how infections detected by HPV and cytology
      wax and wane relative to each other. The aim of this analysis was to assess the
      longitudinal relationship of abnormal cytology and HPV positivity in a 7-year
      prospective study of 2500 women in Guanacaste, Costa Rica. METHODS: At each
      semiannual or annual visit, cervical specimens were screened using liquid-based
      cytology and tested for >40 HPV types with use of MY09/MY11 L1 degenerate primer
      polymerase chain reaction-based methods. On the basis of previous work, we
      separated prevalent and newly detected infections in younger and older women.
      RESULTS: Among newly detected HPV- and/or cytology-positive events, HPV and
      cytology appeared together ~60% of the time; when discordant, HPV tended to
      appear before cytology in younger and older women. Combining newly and
      prevalently detected events, HPV and cytology disappeared at the same time >70%
      of the time. When discordant, HPV tended to disappear after cytology in younger
      and older women. CONCLUSIONS: Detection of HPV DNA and associated cytological
      abnormalities tend to come and leave together; however, when discordant,
      detection of HPV DNA tends to precede and/or last longer than associated
      cytologic abnormalities.

PMID- 22147793
TI  - Transmission of the X4 phenotype of HIV-1: is there evidence against the "random
      transmission" hypothesis?

PMID- 22147795
TI  - Preventing deaths in persons with HIV/hepatitis B virus coinfection: a call to
      accelerate prevention and treatment efforts.

PMID- 22147794
TI  - Hepatitis B virus coinfection negatively impacts HIV outcomes in HIV
      seroconverters.
AB  - BACKGROUND: Understanding the impact of hepatitis B virus (HBV) in human
      immunodeficiency virus (HIV) coinfection has been limited by heterogeneity of HIV
      disease. We evaluated HBV coinfection and HIV-related disease progression in a
      cohort of HIV seroconverters. METHODS: Participants with HIV diagnosis
      seroconversion window of <= 3 years and serologically confirmed HBV infection
      (HB) status were classified at baseline into 4 HB groups. The risk of clinical
      AIDS/death in HIV seroconverters was calculated by HB status. RESULTS: Of 2352
      HIV seroconverters, 474 (20%) had resolved HB, 82 (3%) had isolated total
      antibody to hepatitis B core antigen (HBcAb), and 64 (3%) had chronic HB.
      Unadjusted rates (95% confidence intervals [CIs]) of clinical AIDS/death for the
      HB-negative, resolved HB, isolated HBcAb, and chronic HB groups were 2.43 (2.15
      2.71); 3.27 (2.71-3.84); 3.75 (2.25-5.25); and 5.41 (3.41-7.42), respectively.
      The multivariable risk of clinical AIDS/death was significantly higher in the
      chronic HB group compared to the HB-negative group (hazard ratio [HR], 1.80; 95%
      CI, 1.20-2.69); while the HRs were increased but nonsignificant for those with
      resolved HB (HR, 1.17; 95% CI, .94-1.46) and isolated HBcAb (HR, 1.14; 95% CI,
      .75-1.75). CONCLUSIONS: HBV coinfection has a significant impact on HIV outcomes.
      The hazard for an AIDS or death event is almost double for those with chronic HB
      compared, with HIV-monoinfected persons.

PMID- 22147796
TI  - Male circumcision and herpes simplex virus type 2 infection in female partners: a
      randomized trial in Rakai, Uganda.
AB  - Male circumcision reduces acquisition of herpes simplex virus type 2 (HSV-2) in
      men. We assessed whether male circumcision reduces HSV-2 infection among female
      partners. HSV-2-negative, human immunodeficiency virus-negative female partners
      of 368 males who were and 372 males who were not randomized to receive male
      circumcision were enrolled. The incidence of HSV-2 infection among females over a
      period of 2 years was 6.09 cases per 100 person-years in the intervention arm and
      6.32 cases per 100 person-years in the control arm (incidence rate ratio [IRR],
      0.96 [95% confidence interval {CI}, .62-1.49]; P = .87). Among female partners of
      HSV-2-positive males, the incidence of HSV-2 infection was 9.55 cases per 100
      person-years in the intervention arm and 11.17 cases per 100 person-years in the
      control arm (IRR, 0.85 [95% CI, .44-1.67]; P = .62). Contrary to findings in
      males, male circumcision did not affect HSV-2 acquisition among female partners.

PMID- 22147797
TI  - Influenza and obesity: will vaccines and antivirals protect?

PMID- 22147798
TI  - Systemic dissemination of Clostridium difficile toxins A and B is associated with
      severe, fatal disease in animal models.
AB  - BACKGROUND: Clostridium difficile infection (CDI) can cause a wide range of
      disease, from mild diarrhea to fulminant systemic disease. The incidence of
      systemic CDI with fatal consequence has increased rapidly in recent years.
      METHODS: Using an ultrasensitive cytotoxicity assay, we measured C. difficile
      toxin A (TcdA) and C. difficile toxin B (TcdB) in sera and body fluids of piglets
      and mice exposed to C. difficile to investigate the relationship between the
      presence of toxins in body fluids and systemic manifestations of CDI. RESULTS: We
      found that both TcdA and TcdB disseminate systemically, with toxins present in
      the sera and body fluids of infected animals, and toxemia is significantly
      correlated with the development of systemic CDI. The systemic administration of
      neutralizing antibodies against both toxins blocked the development of systemic
      disease in mice. We measured cytokine concentrations in the sera of mice and
      piglets with systemic and nonsystemic CDI and found that proinflammatory
      mediators were considerably elevated in animals with systemic CDI. CONCLUSION:
      Our study demonstrates the existence of a strong correlation between toxemia and
      the occurrence of systemic disease, supporting the hypothesis that systemic CDI
      is most likely due to the toxicity of TcdA and TcdB and the induction of
      proinflammatory cytokines by the toxins.

PMID- 22147800
TI  - Clostridium difficile toxins and severe C. difficile infection.

PMID- 22147799
TI  - Impaired wound healing predisposes obese mice to severe influenza virus
      infection.
AB  - For the first time, obesity appeared as a risk factor for developing severe 2009
      pandemic influenza infection. Given the increase in obesity, there is a need to
      understand the mechanisms underlying poor outcomes in this population. In these
      studies, we examined the severity of pandemic influenza virus in obese mice and
      evaluated antiviral effectiveness. We found that genetically and diet-induced
      obese mice challenged with either 2009 influenza A virus subtype H1N1 or 1968
      subtype H3N2 strains were more likely to have increased mortality and lung
      pathology associated with impaired wound repair and subsequent pulmonary edema.
      Antiviral treatment with oseltamivir enhanced survival of obese mice. Overall,
      these studies demonstrate that impaired wound lung repair in the lungs of obese
      animals may result in severe influenza virus infection. Alternative approaches to
      prevention and control of influenza may be needed in the setting of obesity.

PMID- 22147801
TI  - Diet-induced obesity dramatically reduces the efficacy of a 2009 pandemic H1N1
      vaccine in a mouse model.
AB  - BACKGROUND: Obesity, a risk factor for increased severity of diverse diseases, is
      believed to have negative impact on vaccine efficacy. Recently, mortality has
      emerged as an outcome of pandemic influenza A virus subtype H1N1, necessitating
      development of effective vaccine strategies. Here we investigated effects of diet
      induced obesity on vaccine-induced immune responses and protective efficacy
      against pandemic H1N1 influenza virus. METHODS: Diet-induced obese and lean
      C57BL/6J mice were immunized with commercial monovalent 2009 H1N1 vaccine, and
      antigen-specific antibody responses and neutralizing activities were observed.
      Following vaccination, mice were challenged with homologous H1N1 virus, and
      pathogenesis and mortality were examined. RESULTS: Vaccine-induced H1N1-specific
      antibody responses and neutralizing activities were markedly reduced in obese
      mice. Consistent with antibody responses, lung virus titers were significantly
      higher in obese mice than in lean controls after challenge. In addition, obese
      group showed greatly increased expression of proinflammatory cytokines and
      chemokines in lung tissue, severe lung inflammation, and higher eventual
      mortality rate (100%) compared with that among lean control mice (14%).
      CONCLUSIONS: Our results show that prophylactic immune responses and
      protectiveness induced by 2009 H1N1 vaccine could be extremely compromised in
      diet-induced obesity. These results suggest that novel vaccination strategies for
      high-risk groups, including the obese population, are required.

PMID- 22147802
TI  - Presence of CXCR4-using HIV-1 in patients with recently diagnosed infection:
      correlates and evidence for transmission.
AB  - BACKGROUND: The prevalence and correlates of CXCR4-use in recently diagnosed
      patients and the impact of X4/DM transmission remain largely unknown. METHOD:
      Genotypic coreceptor use determination on the baseline sample of 539 recently
      diagnosed individuals. Correlation of coreceptor use with clinical, viral and
      epidemiological data and with information on transmission events as obtained
      through phylogenetic analysis of protease and reverse transcriptase sequences.
      Results. CXCR4-use was predicted in 12 to 19% of the patients, depending on the
      interpretative cutoff used. CXCR4-use was correlated with lower CD4(+) T cell
      counts and subtype 01_AE infection. No association with viral load was observed.
      Seven (11%) of 63 transmission clusters and 4 (31%) of 13 donor-source pairs
      resulted from X4/DM transmission. CONCLUSION: The results confirmed the relation
      between CXCR4-use at diagnosis and low baseline CD4+ T cell counts. Significantly
      more CXCR4-use was predicted in 01_AE infections, which may impose constraints on
      the use of CCR5 antagonists in certain regions of the world. Observations from
      the transmission cluster analysis contradict the hypothesis that R5 viruses are
      selected at transmission, and support the idea that R5 or X4/DM infections result
      from a stochastic process.

PMID- 22147803
TI  - Lymphoma study group of JCOG.
AB  - The Lymphoma Study Group (LSG) of the Japan Clinical Oncology Group (JCOG) was
      initiated in 1978 by five institutions and now has 47 members. JCOG-LSG has
      focused on combined modalities, dose intensification and the incorporation of new
      agents for major disease entities of lymphoid malignancies. More than 30 trials
      including 10 randomized trials have been conducted for aggressive non-Hodgkin's
      lymphoma (NHL), adult T-cell leukemia-lymphoma (ATL), lymphoblastic
      lymphoma/acute lymphoblastic leukemia, Hodgkin's lymphoma (HL), multiple myeloma,
      NK/T-NHL and indolent B-NHL, and correlative epidemiological and pathological
      studies have been performed on human T-lymphotropic virus type-I and T/B cell
      phenotypes. The first trials for aggressive NHL revealed significant differences
      in the prognosis of ATL, non-ATL T-NHLs and B-NHLs, establishing a
      subclassification of ATL, and leading to the establishment of standard therapies
      for ATL and localized nasal natural killer/T-NHL. Recently, for B-NHLs including
      diffuse large B-cell lymphoma, mantle cell lymphoma, and indolent B-NHLs,
      regimens incorporating rituximab have been evaluated. The JCOG-LSG trials for HL
      led to the approval of dacarbazine for the National Health Insurance in Japan.
      The multicenter trials by the JCOG-LSG combining new modalities such as molecular
      targeting agents will contribute to further improvements in the treatment of
      lymphoid malignancies.

PMID- 22147804
TI  - Does p63RhoGEF, a new key mediator of angiotensin II signalling, play a role in
      blood pressure regulation and cardiovascular remodelling in humans?

PMID- 22147805
TI  - When the (pro)renin receptor leaves an acidic taste.

PMID- 22147806
TI  - Current knowledge of (pro)renin receptor as an accessory protein of vacuolar H+
      ATPase.
AB  - The (pro)renin receptor (P)RR is a receptor for renin and prorenin, not only
      allowing local production of angiotensin I from angiotensinogen, but also
      inducing intracellular signaling. Intriguingly, (P)RR is also called ATP6AP2
      because a (P)RR fragment was demonstrated to be associated with vacuolar-type H+
      ATPase (V-ATPase), which is of importance for the maintenance of intracellular
      pH. Recent studies implicate that deletion of (P)RR results in the dysfunction of
      V-ATPase, suggesting that the (P)RR is essential for its role as a proton pump.
      Furthermore, the novel function of (P)RR as an adaptor protein between the Wnt
      receptor complex and the V-ATPase was discovered. Thus, (P)RR is a multi
      functional molecule with functions beyond renin and prorenin. This review focuses
      on the current knowledge and issues of (P)RR and V-ATPase.

PMID- 22147807
TI  - Psychiatric disorders with postpartum onset: possible early manifestations of
      bipolar affective disorders.
AB  - CONTEXT: Childbirth has an important influence on the onset and course of bipolar
      affective disorder, and it is well established that there may be a delay of many
      years before receiving a diagnosis of bipolar disorder following an initial
      episode of psychiatric illness. OBJECTIVE: To study to what extent psychiatric
      disorders with postpartum onset are early manifestations of an underlying bipolar
      affective disorder. DESIGN: Survival analyses were performed in a register-based
      cohort study linking information from the Danish Civil Registration System and
      the Danish Psychiatric Central Register. SETTING: Denmark. PARTICIPANTS: A total
      of 120,378 women with a first-time psychiatric inpatient or outpatient contact
      with any type of mental disorder excluding bipolar affective disorder. MAIN
      OUTCOME MEASURES: Each woman was followed up individually from the day of
      discharge, with the outcome of interest being an inpatient or outpatient contact
      during the follow-up period with a first-time diagnosis of bipolar affective
      disorder. RESULTS: A total of 3062 women were readmitted or had an outpatient
      contact with bipolar affective disorder diagnoses. A postpartum onset of symptoms
      within 0 to 14 days after delivery predicted subsequent conversion to bipolar
      disorder (relative risk = 4.26; 95% CI =3.11-5.85). Approximately 14% of women
      with first-time psychiatric contacts during the first postpartum month converted
      to a bipolar diagnosis within the 15-year follow-up period compared with 4% of
      women with a first psychiatric contact not related to childbirth. Postpartum
      inpatient admissions were also associated with higher conversion rates to bipolar
      disorder than outpatient contacts (relative risk = 2.16; 95% CI = 1.27-3.66).
      CONCLUSIONS: A psychiatric episode in the immediate postpartum period
      significantly predicted conversion to bipolar affective disorder during the
      follow-up period. Results indicate that the presentation of mental illness in the
      early postpartum period is a marker of possible underlying bipolarity.

PMID- 22147808
TI  - Prevalence, persistence, and sociodemographic correlates of DSM-IV disorders in
      the National Comorbidity Survey Replication Adolescent Supplement.
AB  - CONTEXT: Community epidemiological data on the prevalence and correlates of
      adolescent mental disorders are needed for policy planning purposes. Only limited
      data of this sort are available. OBJECTIVE: To present estimates of 12-month and
      30-day prevalence, persistence (12-month prevalence among lifetime cases and 30
      day prevalence among 12-month cases), and sociodemographic correlates of commonly
      occurring DSM-IV disorders among adolescents in the National Comorbidity Survey
      Replication Adolescent Supplement. DESIGN: The National Comorbidity Survey
      Replication Adolescent Supplement is a US national survey of DSM-IV anxiety,
      mood, behavior, and substance disorders among US adolescents based on face-to
      face interviews in the homes of respondents with supplemental parent
      questionnaires. SETTING: Dual-frame household and school samples of US
      adolescents. PARTICIPANTS: A total of 10,148 adolescents aged 13 to 17 years
      (interviews) and 1 parent of each adolescent (questionnaires). MAIN OUTCOME
      MEASURES: The DSM-IV disorders assessed with the World Health Organization
      Composite International Diagnostic Interview and validated with blinded clinical
      interviews based on the Schedule for Affective Disorders and Schizophrenia for
      School-Age Children. Good concordance (area under the receiver operating
      characteristic curve >=0.80) was found between Composite International Diagnostic
      Interview and Schedule for Affective Disorders and Schizophrenia for School-Age
      Children diagnoses. RESULTS: The prevalence estimates of any DSM-IV disorder are
      40.3% at 12 months (79.5% of lifetime cases) and 23.4% at 30 days (57.9% of 12
      month cases). Anxiety disorders are the most common class of disorders, followed
      by behavior, mood, and substance disorders. Although relative disorder prevalence
      is quite stable over time, 30-day to 12-month prevalence ratios are higher for
      anxiety and behavior disorders than mood or substance disorders, suggesting that
      the former are more chronic than the latter. The 30-day to 12-month prevalence
      ratios are generally lower than the 12-month to lifetime ratios, suggesting that
      disorder persistence is due more to episode recurrence than to chronicity.
      Sociodemographic correlates are largely consistent with previous studies.
      CONCLUSIONS: Among US adolescents, DSM-IV disorders are highly prevalent and
      persistent. Persistence is higher for adolescents than among adults and appears
      to be due more to recurrence than chronicity of child-adolescent onset disorders.

PMID- 22147809
TI  - Association of depression with increased risk of dementia in patients with type 2
      diabetes: the Diabetes and Aging Study.
AB  - CONTEXT: Although depression is a risk factor for dementia in the general
      population, its association with dementia among patients with diabetes mellitus
      has not been well studied. OBJECTIVE: To determine whether comorbid depression in
      patients with type 2 diabetes increases the risk of development of dementia.
      DESIGN: The Diabetes and Aging Study was a cohort investigation that surveyed a
      racially/ethnically stratified random sample of patients with type 2 diabetes.
      SETTING: A large, integrated, nonprofit managed care setting in Northern
      California. PARTICIPANTS: A sample of 19,239 diabetes registry members 30 to 75
      years of age. MAIN OUTCOME MEASURES: The Patient Health Questionnaire 8,
      International Classification of Diseases, Ninth Revision (ICD-9) diagnoses of
      depression, and/or antidepressant prescriptions in the 12 months prior to
      baseline were used to identify prevalent cases of depression. Clinically
      recognized dementia was identified among subjects with no prior ICD-9 Clinical
      Modification (ICD-9-CM) diagnoses of dementia. To exclude the possibility that
      depression was a prodrome of dementia, dementia diagnoses were only based on ICD
      9-CM diagnoses identified in years 3 to 5 postbaseline. The risk of dementia for
      patients with depression and diabetes relative to patients with diabetes alone
      was estimated using Cox proportional hazard regression models that adjusted for
      sociodemographic, clinical, and health risk factors and health use. RESULTS:
      During the 3- to 5-year period, 80 of 3766 patients (2.1%) with comorbid
      depression and diabetes (incidence rate of 5.5 per 1000 person-years) vs 158 of
      15,473 patients (1.0%) with diabetes alone (incidence rate of 2.6 per 1000 person
      years) had 1 or more ICD-9-CM diagnoses of dementia. Patients with comorbid
      depression had a 100% increased risk of dementia during the 3 to 5 years
      postbaseline (adjusted hazard ratio, 2.02; 95% confidence interval, 1.73-2.35).
      CONCLUSION: Depression in patients with diabetes was associated with a
      substantively increased risk for development of dementia compared with those with
      diabetes alone.

PMID- 22147810
TI  - Evidence for chronically altered serotonin function in the cerebral cortex of
      female 3,4-methylenedioxymethamphetamine polydrug users.
AB  - CONTEXT: MDMA (3,4-methylenedioxymethamphetamine, also popularly known as
      "ecstasy") is a popular recreational drug that produces loss of serotonin axons
      in animal models. Whether MDMA produces chronic reductions in serotonin signaling
      in humans remains controversial. OBJECTIVE: To determine whether MDMA use is
      associated with chronic reductions in serotonin signaling in the cerebral cortex
      of women as reflected by increased serotonin(2A) receptor levels. DESIGN: Cross
      sectional case-control study comparing serotonin(2A) receptor levels in abstinent
      female MDMA polydrug users with those in women who did not use MDMA (within-group
      design assessing the association of lifetime MDMA use and serotonin(2A)
      receptors). Case participants were abstinent from MDMA use for at least 90 days
      as verified by analysis of hair samples. The serotonin(2A) receptor levels in the
      cerebral cortex were determined using serotonin(2A)-specific positron emission
      tomography with radioligand fluorine 18-labeled setoperone as the tracer.
      SETTING: Academic medical center research laboratory. PARTICIPANTS: A total of 14
      female MDMA users and 10 women who did not use MDMA (controls). The main
      exclusion criteria were nondrug-related DSM-IV Axis I psychiatric disorders and
      general medical illness. MAIN OUTCOME MEASURES: Cortical serotonin(2A) receptor
      nondisplaceable binding potential (serotonin(2A)BP(ND)). RESULTS: MDMA users had
      increased serotonin(2A)BP(ND) in occipital-parietal (19.7%), temporal (20.5%),
      occipitotemporal-parietal (18.3%), frontal (16.6%), and frontoparietal (18.5%)
      regions (corrected P < .05). Lifetime MDMA use was positively associated with
      serotonin(2A)BP(ND) in frontoparietal (beta = 0.665; P = .007), occipitotemporal
      (beta = 0.798; P = .002), frontolimbic (beta = 0.634; P = .02), and frontal (beta
      = 0.691; P = .008) regions. In contrast, there were no regions in which MDMA use
      was inversely associated with receptor levels. There were no statistically
      significant effects of the duration of MDMA abstinence on serotonin(2A)BP(ND).
      CONCLUSIONS: The recreational use of MDMA is associated with long-lasting
      increases in serotonin(2A) receptor density. Serotonin(2A) receptor levels
      correlate positively with lifetime MDMA use and do not decrease with abstinence.
      These results suggest that MDMA use produces chronic serotonin neurotoxicity in
      humans. Given the broad role of serotonin in human brain function, the
      possibility for therapeutic MDMA use, and the widespread recreational popularity
      of this drug, these results have critical public health implications.

PMID- 22147812
TI  - Weight reduction and improvements in endothelial function: combating the "obesity
      paradox" in coronary heart disease.

PMID- 22147813
TI  - Abdominal compartment syndrome: toward less-invasive management.

PMID- 22147811
TI  - Dendritic cell-associated lectin 2 (DCAL2) defines a distinct CD8alpha- dendritic
      cell subset.
AB  - CLRs on DCs play important roles in immunity and are expressed selectively on
      certain DC subsets. Murine DCAL2 (myeloid inhibitory C-type lectin/Clec12a) is a
      type-II CLR with an ITIM. Using a mouse DCAL2-specific mAb, we found that DCAL2
      is expressed at relatively high levels on APCs and that DCAL2 expression can be
      used to divide CD8alpha- DCs into DCAL2+DCIR2- and DCAL2-DCIR2+ subpopulations.
      CD8alpha-DCAL2+ DC, CD8alpha-DCIR2+ DC, and CD8alpha+DCAL2+ DC subsets each
      express different levels of TLRs and respond to unique classes of TLR ligands by
      producing distinct sets of cytokines. Whereas CD8alpha-DCAL2+ DCs robustly
      produce cytokines, including IL-12, in response to CpG, CD8alpha-DCIR2+ DCs
      produce only TNF-alpha and IL-10 in modest amounts when stimulated with zymosan.
      However, CD8alpha-DCIR2+DCs, unlike the other DC subsets, strongly up-regulate
      OX40L when stimulated with bacterial flagellin. As predicted from their cytokine
      expression, CD8alpha-DCAL2+ DCs efficiently induced Th1 responses in the presence
      of CpG in vitro and in vivo, whereas CD8alpha-DCIR2+ DCs induced Th2 cells in
      response to flagellin. Thus, CD8alpha-DCAL2+ DCs comprise a distinct CD8alpha- DC
      subset capable of supporting Th1 responses. DCAL2 is a useful marker to identify
      a Th1-inducing CD8alpha- DC population.

PMID- 22147814
TI  - Pushing forward into the darkness, leaping, and landing securely: prognostication
      and adjuvant chemotherapy for lung cancer.

PMID- 22147815
TI  - Direct characterization of the vascular endothelium in sleep apnea.

PMID- 22147816
TI  - Thromboprophylaxis in the real world: strengths and limitations of comparative
      effectiveness research.

PMID- 22147817
TI  - Point: should lactate clearance be substituted for central venous oxygen
      saturation as goals of early severe sepsis and septic shock therapy? Yes.

PMID- 22147818
TI  - Counterpoint: should lactate clearance be substituted for central venous oxygen
      saturation as goals of early severe sepsis and septic shock therapy? No.

PMID- 22147819
TI  - Implementing early mobilization interventions in mechanically ventilated patients
      in the ICU.
AB  - As ICU survival continues to improve, clinicians are faced with short- and long
      term consequences of critical illness. Deconditioning and weakness have become
      common problems in survivors of critical illness requiring mechanical
      ventilation. Recent literature, mostly from a medical population of patients in
      the ICU, has challenged the patient care model of prolonged bed rest. Instead,
      the feasibility, safety, and benefits of early mobilization of mechanically
      ventilated ICU patients have been reported in recent publications. The benefits
      of early mobilization include reductions in length of stay in the ICU and
      hospital as well as improvements in strength and functional status. Such benefits
      can be accomplished with a remarkably acceptable patient safety profile. The
      importance of interactions between mind and body are highlighted by these
      studies, with improvements in patient awareness and reductions in ICU delirium
      being noted. Future research to address the benefits of early mobilization in
      other patient populations is needed. In addition, the potential for early
      mobilization to impact long-term outcomes in ICU survivors requires further
      study.

PMID- 22147820
TI  - Critical care rationing: international comparisons.
AB  - Every country has finite resources that are expended to provide citizens with
      social "goods," including education, protection, infrastructure, and health care.
      Rationing-of any resource-refers to distribution of an allotted amount and may
      involve withholding some goods that would benefit some citizens. Health-care
      rationing is controversial because good health complements so many human
      endeavors. We explored (perceptions regarding) critical care rationing in seven
      industrialized countries. Academic physicians from England, Spain, Italy, France,
      Argentina, Canada, and the United States wrote essays that addressed specific
      questions including: (1) What historical, cultural, and medical institutional
      features inform my country's approach to rationing of health care? (2) What is
      known about formal rationing, especially in critical care, in my country? (3) How
      does rationing occur in my ICU? Responses suggest that critical care is rationed,
      by varying mechanisms, in all seven countries. We speculate that while no single
      "best" method of rationing is likely to be acceptable or optimal for all
      countries, professional societies could serve international health by developing
      evidence-based guidelines for just and effective rationing of critical care.

PMID- 22147821
TI  - The ethics and reality of rationing in medicine.
AB  - Rationing is the allocation of scarce resources, which in health care necessarily
      entails withholding potentially beneficial treatments from some individuals.
      Rationing is unavoidable because need is limitless and resources are not. How
      rationing occurs is important because it not only affects individual lives but
      also expresses society's most important values. This article discusses the
      following topics: (1) the inevitability of rationing of social goods, including
      medical care; (2) types of rationing; (3) ethical principles and procedures for
      fair allocation; and (4) whether rationing ICU care to those near the end of life
      would result in substantial cost savings.

PMID- 22147822
TI  - Percutaneous cryoablation for pulmonary nodules in the residual lung after
      pneumonectomy: report of two cases.
AB  - Lung cancers in the residual lungs of patients who have undergone pneumonectomies
      are often unresectable, primarily because of the risks of overt pulmonary
      function losses. Percutaneous cryoablation of lung tumors is a potentially
      minimally invasive technique that has recently been used in the treatment of lung
      cancers and metastatic lung tumors. Here, we present two patients who had
      previously undergone pneumonectomies, in whom lung cancers in the residual lungs
      were treated by cryoablation. In both patients, the procedures were performed
      safely without any complications, such as airway bleeding, hemothoraces, or
      pneumothoraces. The changes in pulmonary functions after the procedures were
      minimal: % vital capacity (-1% and -4%), and %FEV(1) (-1% and +10%) in the first
      and second patients, respectively. The performance statuses were maintained at
      zero in both patients after cryoablation. In the first patient, local control has
      been maintained for 4 years. In the second patient, local control was maintained
      for 2 years until the patient died of distant metastases. This is, to our
      knowledge, the first reported case of lung cryoablation in residual lungs of
      patients who have previously undergone pneumonectomies. Application of
      percutaneous cryoablation may represent a new treatment option for lung tumors in
      patients who have previously undergone pneumonectomies.

PMID- 22147823
TI  - Rising PaCO(2) in the ICU: using a physiologic approach to avoid cognitive
      biases.

PMID- 22147825
TI  - A 32-year-old man with recurrent kidney stones and an abnormal chest radiograph.

PMID- 22147824
TI  - Clostridium difficile in the ICU: the struggle continues.
AB  - Clostridium difficile infection (CDI) management has become more daunting over
      the past decade because of alarming increases in CDI incidence and severity both
      in the hospital and in the community. This increase has concomitantly caused
      significant escalation of the health-care economic burden caused by CDI, and it
      will likely be translated to increased ICU admission and attributable mortality.
      Some possible causes for difficulty in management of CDI are as follows: (1)
      inability to predict and prevent development of severe/complicated or relapsing
      CDI in patients who initially present with mild symptoms; (2) lack of a method to
      determine who would have benefited a priori from initiating vancomycin treatment
      first instead of treatment with metronidazole; (3) lack of sensitive and specific
      CDI diagnostics; (4) changing epidemiology of CDI, including the emergence of a
      hypervirulent, epidemic C difficile strain associated with increased morbidity
      and mortality; (5) association of certain high-usage nonantimicrobial medications
      with CDI; and (6) lack of treatment regimens that leave the normal intestinal
      flora undisturbed while treating the primary infection. The objective of this
      article is to present current management and prevention guidelines for CDI based
      on recommendations by the Society for Healthcare Epidemiology of America and
      Infectious Diseases Society of America and potential new clinical management
      strategies on the horizon.

PMID- 22147826
TI  - An 11-year-old boy with respiratory failure and massive pleural fluid drainage.

PMID- 22147827
TI  - Multigene mutation analysis on cytologic samples.

PMID- 22147828
TI  - Rapid pleurodesis: an outpatient alternative.

PMID- 22147829
TI  - Physician specialty as a source of heterogeneity in the care of patients with
      COPD.

PMID- 22147830
TI  - Procalcitonin vs clinical and chest film findings to diagnose community-acquired
      pneumonia in patients with acute asthma or acute exacerbations of chronic
      bronchitis.

PMID- 22147831
TI  - Conventional ventilation vs protective strategies for thoracic surgery: the
      results may be too good to be true.

PMID- 22147832
TI  - Diagnostic performance of percutaneous core-needle lung biopsy under CT scan
      fluoroscopic guidance for pulmonary lesions measuring <=10 mm.

PMID- 22147833
TI  - Social work in adult critical care: a national survey.

PMID- 22147834
TI  - Unapproved prescription cough, cold, and allergy medications.

PMID- 22147836
TI  - Managing the student with severe food allergies.
AB  - School nurses play a key role in managing students with food allergies. It is
      becoming more common to encounter students with severe allergies to multiple
      foods, putting them at risk for anaphylaxis. It is essential that the school
      nurse have a clear understanding of food allergies and how to effectively manage
      students in the school setting. Effective communication between families, health
      care providers, faculty, staff, and students, is of utmost importance when
      developing a plan of care to ensure the safety of the student with food
      allergies. Using an interdisciplinary approach to case management, the school
      nurse can develop comprehensive individualized health care plans for all students
      with food allergies.

PMID- 22147837
TI  - A longitudinal study of overweight, elevated blood pressure, and acanthosis
      nigricans among low-income middle school students.
AB  - This longitudinal study examined the rates of overweight, elevated blood
      pressure, acanthosis nigricans, and their associated factors in third through
      fifth grade students over 4 years. Participants consisted of 279 students who
      participated in health screenings in 2002 and 2006. Hispanic students had
      significantly higher rates of overweight and acanthosis nigricans compared to
      White students. There was a sharp increase in elevated blood pressure from 2002
      to 2006 among obese children. While 20% of the matched obese students were above
      the 90th percentile in 2002, 82% of the same students were above the 90th
      percentile in 2006. After controlling for sex, ethnicity, and grade,
      preadolescent obesity in 2002 continued to be a significant factor associated
      with elevated blood pressure and acanthosis nigricans in 2006. These findings
      demonstrate that prevention and treatment of obesity during preadolescence is
      critical for the prevention of elevated high blood pressure in early adolescence.

PMID- 22147838
TI  - Validation of a novel index to assess insulin resistance of adipose tissue
      lipolytic activity in obese subjects.
AB  - Insulin resistance in adipose tissue increases the release of free fatty acids
      into the circulation, which likely contributes to impaired insulin action in
      liver and skeletal muscle associated with obesity. However, reliable assessment
      of adipose tissue insulin resistance requires performing a hyperinsulinemic
      euglycemic clamp procedure in conjunction with a fatty acid tracer infusion to
      determine insulin-mediated suppression of lipolytic rate. We developed a simpler
      method for evaluating adipose tissue insulin resistance in vivo, determined as
      the product of palmitate rate of appearance into the bloodstream and plasma
      insulin concentration during basal conditions. We validated our Adipose Tissue
      Insulin Resistance Index (ATIRI) by comparison with an assessment of adipose
      tissue insulin resistance determined by using the hyperinsulinemic-euglycemic
      clamp procedure in conjunction with a palmitate tracer infusion in 47 obese
      nondiabetic subjects (body mass index: 40.1 +/- 9.3 kg/m(2)). We found the ATIRI
      correlated closely with adipose tissue insulin resistance assessed during the
      clamp procedure (r =-0.854, P < 0.001). These results demonstrate that the ATIRI
      provides a reliable index of adipose tissue insulin resistance in obese subjects.

PMID- 22147840
TI  - Andrei Rublev's Old Testament Trinity.

PMID- 22147839
TI  - Catheter ablation of right atrial ganglionated plexi in patients with vagal
      paroxysmal atrial fibrillation.
AB  - BACKGROUND: Catheter ablation of ganglionated plexi (GP) in the left atrium has
      been proposed in different subgroup of patients with atrial fibrillation (AF).
      Anatomic studies found a high prevalence of GP in the posterior surface of the
      right atrium (RA). Experimental data suggested the potential role of right atrial
      GP in the AF initiation and maintenance. The aim of our study was to assess the
      efficacy of GP ablation in RA in patients with vagal AF. METHODS AND RESULTS:
      Thirty-four patients without structural heart diseases were randomly assigned for
      a selective ablation procedure targeted on the elimination of vagal reflex evoked
      by high frequency stimulation or an extensive approach at anatomic sites of GP.
      All patients underwent Holter ECG and heart rate variability evaluation at
      baseline and at 3, 6, 12, and 18 months of follow-up. At a mean follow-up of
      19.7+/-5.2 months, AF recurred in 5 of 17 patients with anatomic ablation and in
      13 of 17 patients with a selective approach (P=0.01). No patient had major
      complications. After ablation, heart rate variability parameters showed a
      significant parasympathetic (and sympathetic) denervation in the first 6 months,
      which was more prominent in patients with anatomic GP ablation and in those
      without AF recurrence. CONCLUSIONS: This study demonstrates that in a selected
      population of vagal paroxysmal AF, the anatomic ablation of GPs in the RA is
      effective in about 70% of patients. These results confirm that atrial vagal
      denervation can abolish AF, as suggested by experimental and clinical data.

PMID- 22147841
TI  - Ten-year trends in quality of care and spending for depression: 1996 through
      2005.
AB  - CONTEXT: During the past decade, the introduction of generic versions of newer
      antidepressants and the release of Food and Drug Administration warnings
      regarding suicidality in children, adolescents, and young adults may have had an
      effect on cost and quality of depression treatment. OBJECTIVES: To examine
      longitudinal trends in health service utilization, spending, and quality of care
      for depression. DESIGN: Observational trend study. SETTING: Florida Medicaid
      enrollees, between July 1, 1996, and June 30, 2006. Patients  Annual cohorts aged
      18 to 64 years diagnosed as having depression. MAIN OUTCOME MEASURES: Mental
      health care spending (adjusted for inflation and case mix), as well as its
      components, including inpatient, outpatient, and medication expenditures. Quality
      of-care measures included medication adherence, psychotherapy, and follow-up
      visits. RESULTS: Mental health care spending increased from a mean of $2802 per
      enrollee to $3610 during this period (29% increase). This increase occurred
      despite a mean decrease in inpatient spending from $641 per enrollee to $373 and
      was driven primarily by an increase in pharmacotherapy spending (up 110%), the
      bulk of which was due to spending on antipsychotics (949% increase). The
      percentage of enrollees with depression who were hospitalized decreased from 9.1%
      to 5.1%, and the percentage who received psychotherapy decreased from 56.6% to
      37.5%. Antidepressant use increased from 80.6% to 86.8%, anxiety medication use
      was unchanged at 62.7% and 64.4%, and antipsychotic use increased from 25.9% to
      41.9%. Changes in quality of care were mixed, with antidepressant use improving
      slightly, psychotherapy utilization fluctuating, and follow-up visits decreasing.
      CONCLUSIONS: During a 10-year period, spending for Medicaid enrollees with
      depression increased substantially, with minimal improvements in quality of care.
      Antipsychotic use contributed significantly to the increase in spending, while
      contributing little to traditional measures of quality of care.

PMID- 22147843
TI  - Reinforcement learning and Gilles de la Tourette syndrome: dissociation of
      clinical phenotypes and pharmacological treatments.
AB  - CONTEXT: Gilles de la Tourette syndrome (GTS) is a hyperkinetic movement disorder
      with heterogeneous phenotypic expression ranging from simple motor and vocal tics
      to more complex tics associated with psychiatric comorbidities. The heterogeneity
      of clinical phenotypes may relate to the dysfunction of distinct frontal cortex
      basal ganglia circuits. OBJECTIVES: To assess the hypothesis that simple motor
      tics and comorbid obsessive-compulsive disorders are associated with dysfunction
      of motor and reward circuits, respectively, and to assess the effects of various
      antipsychotic medications because they are known to reduce motor tics and
      interact with dopamine-related reward processing. DESIGN: Sixty patients with GTS
      were divided into different subgroups depending on their clinical phenotypes and
      pharmacological treatments. The GTS patients and healthy control subjects
      underwent functional magnetic resonance imaging while they performed an
      instrumental learning task that involved adjusting choices between 2 responses
      (left- or right-hand movements) based on outcomes (reward or no reward). SETTING:
      Reference center for GTS, Centre de NeuroImagerie de recherche (CENIR) Paris,
      France. Patients  Sixty GTS patients and 50 controls. RESULTS: Movement-related
      activation in motor circuits was diminished in GTS patients with simple tics
      only. Reward-related activation in limbic circuits was independently reduced by
      the following 2 factors: the presence of associated obsessive-compulsive symptoms
      (mostly compulsions) and the presence of medication with typical antipsychotics
      (dopamine receptor antagonists). Computational modeling with standard
      reinforcement learning algorithms indicated that, for both factors, the
      diminished reward-related activation could account for the impaired choice
      performance. Reinforcement learning was not affected by aripiprazole, a recent
      medication that acts as a partial dopamine agonist. CONCLUSIONS: These results
      support the hypothesized correspondence between clinical phenotypes and frontal
      cortex-basal ganglia circuits. Antipsychotic treatment effects comply with formal
      conceptions that dopamine serves as a teaching signal for reinforcement learning.
      Furthermore, we suggest that, unlike typical antipsychotics, aripiprazole may
      preserve reward sensitivity and hence avoid blunting motivational drives.

PMID- 22147842
TI  - Trajectories of depression severity in clinical trials of duloxetine: insights
      into antidepressant and placebo responses.
AB  - CONTEXT: The high percentage of failed clinical trials in depression may be due
      to high placebo response rates and the failure of standard statistical approaches
      to capture heterogeneity in treatment response. OBJECTIVE: To assess whether
      growth mixture modeling can provide insights into antidepressant and placebo
      responses in clinical trials of patients with major depression. DESIGN: We
      reanalyzed clinical trials of duloxetine to identify distinct trajectories of
      Hamilton Scale for Depression (HAM-D) scores during treatment. We analyzed the
      trajectories in the entire sample and then separately in all active arms and in
      all placebo arms. Effects of duloxetine hydrochloride, selective serotonin
      reuptake inhibitor (SSRI), and covariates on the probability of following a
      particular trajectory were assessed. Outcomes in different trajectories were
      compared using mixed-effects models. SETTING: Seven randomized double-blind
      clinical trials of duloxetine vs placebo and comparator SSRI. Patients A total of
      2515 patients with major depression. INTERVENTIONS: Duloxetine and comparator
      SSRI. Main Outcome Measure Total score on the HAM-D. RESULTS: In the entire
      sample and in the antidepressant-treated subsample, we identified trajectories of
      responders (76.3% of the sample) and nonresponders (23.7% of the sample).
      However, placebo-treated patients were characterized by a single response
      trajectory. Duloxetine and SSRI did not differ in efficacy, and compared with
      placebo they significantly decreased the odds of following the nonresponder
      trajectory. Antidepressant responders had significantly better HAM-D scores over
      time than placebo-treated patients, but antidepressant nonresponders had
      significantly worse HAM-D scores over time than the placebo-treated patients.
      CONCLUSIONS: Most patients treated with serotonergic antidepressants showed a
      clinical trajectory over time that is superior to that of placebo-treated
      patients. However, some patients receiving these medications did more poorly than
      patients receiving placebo. These data highlight the importance of ongoing
      monitoring of medication risks and benefits during serotonergic antidepressant
      treatment. They should further stimulate the search for biomarkers or other
      predictors of responder status in guiding antidepressant treatment.

PMID- 22147844
TI  - Early risk factors for hyperactivity-impulsivity and inattention trajectories
      from age 17 months to 8 years.
AB  - CONTEXT: Attention-deficit/hyperactivity disorder is an etiologically
      heterogeneous neurodevelopmental condition with long-term negative outcomes.
      However, the early developmental course of hyperactivity-impulsivity and
      inattention symptoms and their association with previous environmental risk
      factors are still poorly understood OBJECTIVES: To describe the developmental
      trajectories of hyperactivity-impulsivity and inattention symptoms and to
      identify their prenatal, perinatal, and postnatal risk factors. DESIGN: Birth
      cohort from the general population. SETTING: Quebec Longitudinal Study of Child
      Development. PARTICIPANTS: The sample consisted of 2057 individuals, followed up
      from age 5 months to 8 years. MAIN OUTCOME MEASURES: Prenatal, perinatal, and
      postnatal risk factors assessed at age 5 months were considered predictors of
      group membership in high hyperactivity-impulsivity and inattention trajectories
      from age 17 months to 8 years. RESULTS: The frequency of hyperactivity
      impulsivity symptoms tended to slightly decrease with age, whereas the frequency
      of inattention symptoms substantially increased up to age 6 years. However,
      trajectories of hyperactivity-impulsivity and inattention symptoms were
      significantly associated with each other. Risk factors for high trajectories of
      both types of symptoms were premature birth (adjusted odds ratio [aOR], 1.93; 95%
      CI, 1.07-3.50), low birth weight (2.11; 1.12-3.98), prenatal tobacco exposure
      (1.41; 1.03-1.93), nonintact family (1.85; 1.26-2.70), young maternal age at
      birth of the target child (1.78; 1.17-2.69), paternal history of antisocial
      behavior (1.78; 1.28-2.47), and maternal depression (1.35; 1.18-1.54).
      CONCLUSIONS: A large range of early risk factors, including prenatal, perinatal
      social, and parental psychopathology variables, act independently to heighten the
      likelihood of having persistently high levels of hyperactivity-impulsivity and
      inattention symptoms from infancy to middle childhood. Early interventions should
      be experimented with to provide effective tools for attention
      deficit/hyperactivity disorder prevention.

PMID- 22147846
TI  - Urinary monocyte chemoattractant protein 1 and alpha 1 acid glycoprotein as
      biomarkers of renal disease activity in juvenile-onset systemic lupus
      erythematosus.
AB  - A higher proportion of patients with juvenile-onset systemic lupus erythematosus
      (JSLE) will have renal involvement compared with adult-onset disease, some
      progressing to renal failure in adulthood. Histological examination is the gold
      standard for diagnosing lupus nephritis (LN), but its invasive nature limits
      routine use. Using cross-sectional cohort analysis, we aimed to determine whether
      urinary concentrations of monocyte chemoattractant protein-1 (MCP1), alpha-1-acid
      glycoprotein (AGP) and interferon-inducible protein 10 (IP10) are biomarkers of
      active LN. Sixty JSLE patients recruited to the UK JSLE Cohort Study were
      categorized according to the British Isles Lupus Assessment Group (BILAG)
      activity index. Patients with active renal JSLE (n = 8; renal BILAG score A, B)
      had significantly higher urinary MCP1 concentrations than patients with inactive
      renal disease (n = 52; renal BILAG score C, D, E; 582 pg/mg creatinine [Cr], 207
      pg/mg Cr; p = 0.018) or healthy controls (n = 23; 117 pg/mg Cr; p = 0.005).
      Urinary AGP concentration was significantly elevated in patients with active
      renal disease compared with inactive renal disease (1517 ng/mg Cr, 485 ng/mg Cr;
      p = 0.027) or healthy controls (313 ng/mg Cr; p = 0.013). Urinary IP10
      concentration was not significantly different between groups, but did strongly
      correlate with uMCP and uAGP levels (rho = 0.38, p = 0.009; rho = 0.33, p =
      0.021). Urinary MCP1 and AGP are biomarkers of LN, providing insight into its
      pathophysiology. Longitudinal studies are warranted.

PMID- 22147845
TI  - Migration from Mexico to the United States and conduct disorder: a cross-national
      study.
AB  - CONTEXT: Twin studies suggest that conduct disorder (CD) is under substantial
      genetic influence, which is stronger for aggressive than for nonaggressive
      symptoms. Studies of migrating populations offer an alternative strategy for
      separating environmental and genetic influences on psychiatric disorders.
      OBJECTIVES: To examine variation in the prevalence of CD associated with
      migration from Mexico to the United States and to determine whether this
      variation is similar for aggressive and nonaggressive CD symptoms and symptom
      profiles. DESIGN: The prevalences of CD, different types of CD symptoms, and CD
      symptom profiles were compared across 3 generations of people of Mexican origin
      with increasing levels of exposure to American culture: families of origin of
      migrants (residing in Mexico), children of Mexican migrants raised in the United
      States, and Mexican-American children of US-born parents. SETTING: General
      population surveys conducted in Mexico and the United States using the same
      diagnostic interview. PARTICIPANTS: Adults aged 18 to 44 years in the household
      population of Mexico and the household population of people of Mexican descent in
      the United States. MAIN OUTCOME MEASURES: Conduct disorder criteria, assessed
      using the World Mental Health version of the Composite International Diagnostic
      Interview. RESULTS: Compared with the risk in families of origin of migrants,
      risk of CD was lower in the general population of Mexico (odds ratio [OR], 0.54;
      95% CI, 0.19-1.51), higher in children of Mexican-born immigrants who were raised
      in the United States (OR, 4.12; 95% CI, 1.47-11.52), and higher still in Mexican
      American children of US-born parents (OR, 7.64; 95% CI, 3.20-18.27). The
      association with migration was markedly weaker for aggressive than for
      nonaggressive symptoms. CONCLUSIONS: The prevalence of CD increases dramatically
      across generations of the Mexican-origin population after migration to the United
      States. This increase is of larger magnitude for nonaggressive than for
      aggressive symptoms, consistent with the suggestion that nonaggressive symptoms
      are more strongly influenced by environmental factors than are aggressive
      symptoms.

PMID- 22147848
TI  - Toward a health system that serves patients' interests.

PMID- 22147847
TI  - Inflammasome-IL-1-Th17 response in allergic lung inflammation.
AB  - Allergic asthma has increased dramatically in prevalence and severity over the
      last three decades. Both clinical and experimental data support an important role
      of Th2 cell response in the allergic response. Recent investigations revealed
      that airway exposure to allergen in sensitized individuals causes the release of
      ATP and uric acid, activating the NLRP3 inflammasome complex and cleaving pro-IL
      1beta to mature IL-1beta through caspase-1. The production of pro-IL-1beta
      requires a toll-like receptor (TLR) 4 signal which is provided by the allergen.
      IL-1beta creates a pro-inflammatory milieu with the production of IL-6 and
      chemokines which mobilize neutrophils and enhance Th17 cell differentiation in
      the lung. Here, we review our results showing that NLRP3 inflammasome activation
      is required to develop allergic airway inflammation in mice and that IL-17 and IL
      22 production by Th17 cells plays a critical role in established asthma.
      Therefore, inflammasome activation leading to IL-1beta production contributes to
      the control of allergic asthma by enhancing Th17 cell differentiation.

PMID- 22147849
TI  - Requiem for the CLASS Act.

PMID- 22147850
TI  - Setting priorities for comparative effectiveness research: from assessing public
      health benefits to being open with the public.
AB  - Medicine's current evidence base is insufficient for many of the decisions made
      daily by clinicians, patients, purchasers, and policy makers. The Patient
      Centered Outcomes Research Institute represents an effort by the US government to
      address this shortcoming by funding comparative effectiveness research.
      Prioritizing that research will be a critical first step. To better understand
      components of an optimal process, we reviewed the literature and conducted
      interviews regarding the prioritization efforts of leading public and private
      health organizations in the United States and abroad. From this review, we
      propose a framework for prioritization, pose and answer key questions, and make
      recommendations regarding application of that framework. We also recommend that
      during the priority-setting process, there should be transparent conversations
      among those who make decisions about the priorities and the public.

PMID- 22147851
TI  - How the Patient-Centered Outcomes Research Institute can best influence real
      world health care decision making.
AB  - The Affordable Care Act of 2010 created the Patient-Centered Outcomes Research
      Institute to promote and fund comparative effectiveness research and to ensure
      that the product of this research improves real-world health care decisions.
      Notwithstanding limitations imposed by Congress on the institute's ability to
      influence federal payers' coverage and payment policies, the organization now has
      considerable potential to help standardize and coordinate comparative
      effectiveness research in the United States. Still, many questions remain about
      how this important new entity will function--and a central challenge will be to
      produce comparative effectiveness assessments that can be readily disseminated
      to, and used by, a wide range of health care stakeholders, especially providers
      and patients. I recommend that the institute adopt a comparative effectiveness
      assessment format that compares interventions on the basis of their clinical
      risks and benefits, economic considerations, and the insights they might offer
      into medical care. I also offer an example of how this proposed assessment and
      rating approach might work in the presentation of findings that weigh cardiac
      bypass versus angioplasty as alternatives for the treatment of coronary disease
      in which multiple coronary arteries require intervention.

PMID- 22147852
TI  - The researcher-in-chief at the Patient-Centered Outcomes Research Institute.
      Interview by Susan Dentzer.

PMID- 22147853
TI  - How comparative effectiveness research can help advance 'personalized medicine'
      in cancer treatment.
AB  - The use of biomarkers to "personalize" cancer treatment--identifying discrete
      genes, proteins, or other indicators that can differentiate one type of cancer
      from another and enable the use of highly tailored therapies--offers tremendous
      potential for improved outcomes and lower treatment costs. However, the rapid
      development of cancer biomarker, or genomic, tests--combined with a paucity of
      evidence to support the effectiveness of the tests--presents a challenge for
      patients, clinicians, and other stakeholders. In this article we propose that
      comparative effectiveness research be used to strengthen what is now a haphazard
      process for developing and marketing cancer biomarker tests. We suggest novel
      funding approaches and a systematic process for moving from regulatory approval
      to the generation of evidence that meets the needs of stakeholders and,
      ultimately, patients.

PMID- 22147854
TI  - Can coverage be rescinded when negative trial results threaten a popular
      procedure? The ongoing saga of vertebroplasty.
AB  - To attain the anticipated benefits of increased investments in comparative
      effectiveness research, the results must translate into improved medical practice
      and policy. In this article we present an analysis of a case study of
      percutaneous vertebroplasty, a widely used invasive procedure to treat painful
      vertebral fractures by injecting bone cement into the spine. In August 2009,
      results from a pair of rigorous double-blind randomized controlled trials were
      published and reported that vertebroplasty provided no better pain relief than a
      sham procedure in which needles were introduced into the back without injecting
      cement. More than two years after publication of the two studies, insurers'
      coverage of the procedure continues unchanged. This raises serious questions
      about the policy mechanisms that exist in the United States to interpret and act
      upon "negative" research findings from studies of popular health care
      interventions.

PMID- 22147855
TI  - Registered nurse supply grows faster than projected amid surge in new entrants
      ages 23-26.
AB  - The vast preponderance of the nation's registered nurses are women. In the 1980s
      and 1990 s, a decline in the number of women ages 23-26 who were choosing nursing
      as a career led to concerns that there would be future nurse shortages unless the
      trend was reversed. Between 2002 and 2009, however, the number of full-time
      equivalent registered nurses ages 23-26 increased by 62 percent. If these young
      nurses follow the same life-cycle employment patterns as those who preceded them-
      as they appear to be thus far--then they will be the largest cohort of registered
      nurses ever observed. Because of this surge in the number of young people
      entering nursing during the past decade, the nurse workforce is projected to grow
      faster during the next two decades than previously anticipated. However, it is
      uncertain whether interest in nursing will continue to grow in the future.

PMID- 22147856
TI  - The relative geographic immobility of new registered nurses calls for new
      strategies to augment that workforce.
AB  - Little is known about registered nurses' geographic mobility after they earn
      their first professional degree and become licensed to practice. Through a cross
      sectional mailed survey of newly licensed registered nurses in fifteen states, we
      found that 52.5 percent work within forty miles of where they attended high
      school. Our complementary analysis of Census Bureau data shows that next to
      teaching, nursing is one of the least mobile professions for women, for reasons
      that remain unclear. To ensure that underserved areas have an adequate workforce
      of registered nurses, policy makers should expand the number of educational
      programs in these areas; fund programs that provide incentives to young people
      from these areas to attend nursing programs; consider supporting extension
      programs from accredited nursing schools; and review admission policies for
      nursing programs and the financial aid they offer. If states find it difficult to
      retain out-of-state graduates, giving preference to in-state applicants may make
      sense. Finally, programs and policies that offer financial incentives to attract
      registered nurses to underserved areas, such as the National Health Service Corps
      and the Area Health Education Centers, are critically important. When
      sufficiently funded, such programs could serve to offset the low mobility of new
      registered nurses that we observed.

PMID- 22147857
TI  - US cardiologist workforce from 1995 to 2007: modest growth, lasting geographic
      maldistribution especially in rural areas.
AB  - A sufficient cardiology workforce is necessary to ensure access to cardiovascular
      care. Specifically, access to cardiologists is important in the management and
      treatment of chronic cardiovascular disease. Given this, we examined the supply
      and distribution of the cardiologist workforce. In doing so, we mapped the ratios
      of cardiologists, primary care physicians, and total physicians to the population
      age sixty-five or older within different Hospital Referral Regions from the years
      1995 and 2007. We found that within the twelve-year span of our study, the
      cardiology workforce grew modestly compared with the primary care physician and
      total physician workforces. Also, despite increases in the number of
      cardiologists, there was a persistent geographic maldistribution of the
      workforce. For example, approximately 60 percent of the elderly population had
      access to only 38 percent of the cardiologists. Our results suggest that large
      segments of the US population, specifically in rural and socioeconomically
      disadvantaged areas, continue to have a lower concentration of cardiologists.
      This maldistribution could be addressed through a variety of strategies,
      including the use of telemedicine and economic incentives.

PMID- 22147858
TI  - Clinical decision support systems could be modified to reduce 'alert fatigue'
      while still minimizing the risk of litigation.
AB  - Clinical decision support systems--interactive computer systems that help doctors
      make clinical choices--can reduce errors in drug prescribing by offering real
      time alerts about possible adverse reactions. But physicians and other users
      often suffer "alert fatigue" caused by excessive numbers of warnings about items
      such as potentially dangerous drug interactions. As a result, they may pay less
      attention to or even ignore some vital alerts, thus limiting these systems'
      effectiveness. Designers and vendors sharply limit the ability to modify alert
      systems because they fear being exposed to liability if they permit removal of a
      warning that could have prevented a harmful prescribing error. Our analysis of
      product liability principles and existing research into the use of clinical
      decision support systems, however, finds that more finely tailored or
      parsimonious warnings could ease alert fatigue without imparting a high risk of
      litigation for vendors, purchasers, and users. Even so, to limit liability in
      this area, we recommend stronger government regulation of clinical decision
      support systems and development of international practice guidelines highlighting
      the most important warnings.

PMID- 22147861
TI  - Risk-sharing arrangements that link payment for drugs to health outcomes are
      proving hard to implement.
AB  - Risk-sharing agreements, under which payers and pharmaceutical manufacturers
      agree to link payment for drugs to health outcomes achieved, rather than the
      volume of products used, offer an appealing payment model for pharmaceuticals.
      Although such agreements have been widely touted, the experience to date mainly
      demonstrates how hard they are to implement. Barriers include high implementation
      costs, measurement challenges, and the absence of a suitable data infrastructure.
      Risk-sharing arrangements could gain traction in the United States as payers and
      product manufacturers acquire experience with the concept and as measurement
      techniques and information systems improve. For the foreseeable future, they are
      likely to remain the exception as drug companies pursue payment models
      unconnected to data collection or performance assessment.

PMID- 22147859
TI  - False Claims Act prosecution did not deter off-label drug use in the case of
      neurontin.
AB  - Since 2004 the United States has collected approximately $8 billion from fraud
      enforcement actions against pharmaceutical manufacturers accused under the
      federal False Claims Act of illegally promoting drugs for off-label uses. Using
      the case of gabapentin (Neurontin), a drug approved for epilepsy but prescribed
      for a variety of conditions, we sought to determine whether the enforcement
      action also influenced off-label prescribing rates. We conducted a segmented time
      series analysis using key legal milestones: the initiation of a sealed
      investigation, public announcement of the investigation, and settlement of the
      case. Off-label use grew steadily until settlement, when gabapentin prescriptions
      declined for both off-label and on-label indications. Because enforcement actions
      targeting illegal off-label promotion might not have a substantial deterrent
      effect on prescription rates until after settlement, they should be combined with
      other efforts to combat off-label promotion. These could include additional
      resources for enforcement and a steep increase in penalties because settlements
      to this point have been dwarfed by the financial gains to pharmaceutical
      companies from engaging in improper off-label marketing.

PMID- 22147862
TI  - Despite law, fewer than one in eight completed studies of drugs and biologics are
      reported on time on ClinicalTrials.gov.
AB  - Clinical trial registries are public databases created to prospectively document
      the methods and measures of prescription drug studies and retrospectively collect
      a summary of results. In 2007 the US government began requiring that researchers
      register certain studies and report the results on ClinicalTrials.gov, a public
      database of federally and privately supported trials conducted in the United
      States and abroad. We found that although the mandate briefly increased trial
      registrations, 39 percent of trials were still registered late after the
      mandate's deadline, and only 12 percent of completed studies reported results
      within a year, as required by the mandate. This result is important because there
      is evidence of selective reporting even among registered trials. Furthermore, we
      found that trials funded by industry were more than three times as likely to
      report results than were trials funded by the National Institutes of Health.
      Thus, additional enforcement may be required to ensure disclosure of all trial
      results, leading to a better understanding of drug safety and efficacy. Congress
      should also reconsider the three-year delay in reporting results for products
      that have been approved by the Food and Drug Administration and are in use by
      patients.

PMID- 22147863
TI  - Medicaid cost control measures aimed at second-generation antipsychotics led to
      less use of all antipsychotics.
AB  - "Atypical" or second-generation antipsychotics are a class of drug introduced in
      the 1990 s for the treatment of schizophrenia. Given their growing use and rising
      cost, these and other psychotherapeutic drugs are increasingly subject to prior
      authorization and other restrictions in state Medicaid programs. To evaluate the
      effects of these policies, we collected drug-level information on their use and
      on utilization management strategies--for example, requirements for prior
      authorization, quantity limits, and so-called step therapy--in thirty state
      Medicaid programs between 1999 and 2008. In the eleven states that instituted
      prior authorization during that period, use of atypicals per enrollee rose by 14
      percent, versus 19 percent in the other nineteen states. Prior authorization also
      had spillover effects, in that reduced use of drugs subject to this requirement
      was not fully offset by the substitution of other atypicals or of typical
      antipsychotics. To understand the impact on patients and the resulting use of
      health services, studies should be undertaken of a large, national sample of
      Medicaid enrollees being treated with atypical antipsychotics. Comparative
      effectiveness research should guide physicians and health plans on appropriate
      first treatments, while prior authorization policies should focus on moving
      patients to appropriate second-line therapies when necessary.

PMID- 22147864
TI  - Coverage of newborn and adult male circumcision varies among public and private
      US payers despite health benefits.
AB  - Studies have shown that male circumcision greatly reduces the risk for
      heterosexual transmission of HIV, other sexually transmitted infections, infant
      urinary tract infections, penile cancer, and other adverse health outcomes. Given
      recent data regarding these health benefits and the cost-effectiveness of newborn
      male circumcision, national policy makers are developing new recommendations
      regarding circumcision for newborn, adolescent, and adult males. To investigate
      the implications, this study assessed insurance coverage and reimbursement for
      routine newborn and adult male circumcision in private and public health plans in
      2009. We found that coverage varies across private and public payers. Private
      insurance provides far broader coverage than state Medicaid programs for routine
      newborn male circumcision. Specifically, Medicaid programs in seventeen states do
      not cover it, even though low-income populations have a higher risk of HIV and
      other sexually transmitted diseases compared to higher-income groups. For adult
      male circumcision, coverage is generally sparse across public and private plans.
      Presentation of evidence-based recommendations--for example, from the Centers for
      Disease Control and Prevention--may be necessary if coverage for newborn and
      adult male circumcision is to be expanded.

PMID- 22147865
TI  - Medicare payment cuts for osteoporosis testing reduced use despite tests' benefit
      in reducing fractures.
AB  - Bone imaging known as DXA ("dexa")-dual energy x-ray absorptiometry of the
      central skeleton--is considered the "gold standard" test for osteoporosis, which
      affects more than fifty million Americans. The tests are associated with improved
      clinical outcomes through preventing bone fractures. Cuts in Medicare Part B
      reimbursement for the provision of this preventive imaging in a physician's
      office began in 2007 and reached 56 percent below the 2006 level in January 2010.
      To encourage the use of DXA testing, the Affordable Care Act of 2010 provided
      partial relief from the cuts for two years (2010-11). Our study found that after
      a decade of growth, DXA testing in all Part B settings plateaued in 2007-09,
      resulting in 800,000 fewer tests than expected for Medicare beneficiaries--tests
      that might have prevented approximately 12,000 fractures. Testing declined in
      2010, when the start of reimbursement relief under the Affordable Care Act was
      delayed, and increased outpatient testing failed to offset reduced use in
      physician offices. Our findings strongly suggest that the payment cuts reduced
      beneficiary access and that the tests were underused by elderly female Medicare
      beneficiaries despite strong association with fracture prevention. We recommend
      that Congress extend the payment relief granted under the Affordable Care Act for
      at least another two years.

PMID- 22147866
TI  - Improving coverage for children under health reform will require maintaining
      current eligibility standards for Medicaid and CHIP.
AB  - When the Affordable Care Act of 2010 is fully implemented, it will extend health
      insurance coverage to many adult Americans who currently lack it. It is not
      known, however, how the health reform legislation will affect children and
      parents who would otherwise be uninsured. Based on our analysis, the Affordable
      Care Act has the potential to cut the number of uninsured children by about 40
      percent, from 7.4 million to 4.2 million, and the number of uninsured parents by
      almost 50 percent, from 12.7 million to 6.6 million. However, the actual impact
      will depend on increasing the share of children and parents who are enrolled in
      public coverage and on other implementation outcomes. Most strikingly, if the
      requirement that states continue their Medicaid and Children's Health Insurance
      Program (CHIP) coverage is rescinded and if Congress does not continue funding
      CHIP, the uninsurance rate of children could more than double, increasing from
      4.2 million to 7.9-9.1 million children. In that case, the uninsurance rate among
      children would be higher than if the Affordable Care Act had not been adopted.

PMID- 22147867
TI  - Ohio study shows that insurance coverage is critical for children with special
      health care needs as they transition to adulthood.
AB  - Nearly 30 percent of young adults with special health care needs in Ohio lack
      health insurance, compared to 5 percent of the state's children with special
      health care needs. As children with such needs become too old for Medicaid or
      insurance through their parents' employer, they face great challenges in
      obtaining insurance. Lack of insurance is highly predictive of unmet needs, which
      in turn are predictive of costly hospital-based encounters. Young adults with
      special health care needs who are uninsured are more than twice as likely as
      their peers with insurance to forgo filling prescriptions and getting care and to
      have problems getting care. Even after insurance status is accounted for, young
      adults with special health care needs are more likely than children with such
      needs to not fill prescriptions because of cost and to delay or forgo needed
      care. This study demonstrates that continuous and adequate health insurance is
      vital to the continued well-being of children with special health care needs as
      they transition to young adulthood.

PMID- 22147868
TI  - Quasi-experimental studies suggest that lowering air pollution levels benefits
      infants' and children's health.
AB  - Many human studies have shown a correlation between air pollution and poor health
      in children. This paper focuses on studies that employ quasi-experimental designs
      to study the effects of air pollution on specific populations in an effort to
      isolate the causes and minimize the effect of confounding factors. Human studies
      of many and varied designs have found that exposure to some pollutants, even at
      levels below regulatory thresholds, adversely affects health. Our review of quasi
      experimental studies adds additional support to these findings. Together, the
      research suggests that lowering the thresholds for acceptable air pollution
      levels may be a prudent and necessary step toward improving population health,
      especially among the most vulnerable members of society: infants and children.
      Policy makers should also consider providing specific information to families and
      pregnant women about when and where the risk of pollution exposure is highest, so
      that they can minimize their exposure or avoid it altogether.

PMID- 22147869
TI  - How developing nations can protect children from hazardous chemical exposures
      while sustaining economic growth.
AB  - Increasing worldwide use of chemicals, including heavy metals used in industry
      and pesticides used in agriculture, may produce increases in chronic diseases in
      children unless steps are taken to manage the production, use, trade, and
      disposal of chemicals. In 2020 the developing world will account for 33 percent
      of global chemical demand and 31 percent of production, compared with 23 percent
      and 21 percent, respectively, in 1995. We describe present and potential costs of
      environmental exposures and discuss policy options to protect future generations
      of children in a sustainable development context. Specifically, we describe the
      principles of sound chemicals management, as follows: precaution, or the use of
      cost-effective measures to prevent potentially hazardous exposures before
      scientific understanding is complete; the right to know, or informing the public-
      especially vulnerable groups--in a timely fashion about the safe use of chemicals
      and any releases of chemicals into the environment; pollution prevention, or
      preventing the use of hazardous chemicals and the production of pollutants,
      rather than focusing on managing wastes; internalization of environmental and
      health costs, or ensuring that the consequences of exposures are reflected in the
      price of chemicals through such approaches as "polluter pays"; and use of best
      available scientific information in making decisions such as what chemicals to
      allow into the market. We recommend that industrializing nations in particular
      employ these principles to prevent disease among their populations while at the
      same time minimizing the risk to their own economic development.

PMID- 22147870
TI  - Lessons from San Francisco: health impact assessments have advanced political
      conditions for improving population health.
AB  - Health impact assessment is a structured decision support tool used to
      systematically characterize the anticipated health effects, both adverse and
      beneficial, of societal decisions. In San Francisco, the use of health impact
      assessments has not only produced evidence to inform health policy decision
      making but has also contributed to the political conditions needed to achieve
      optimal population health. Health impact assessments have helped increase public
      awareness of the determinants of health, routine monitoring of these
      determinants, cooperation among institutions, health-protective laws and
      regulations, and organizational networks for health advocacy and accountability.
      Drawing on more than a decade of local experience, we identify the direct and
      indirect effects of the assessments on the politics of governance as well as on
      health. We demonstrate that health impact assessment is both an analytic tool and
      a process that helps build the social institutions that can improve health.

PMID- 22147871
TI  - Health insurance coverage rates in 9 provinces in China doubled from 1997 to
      2006, with a dramatic rural upswing.
AB  - We examined the distribution of health insurance in China during 1997-2006, a
      period when government interventions were implemented to improve access to health
      care. We analyzed data from a survey that follows households in nine provinces
      that are home to more than 40 percent of China's population. The analysis shows
      that the percentage of individuals with insurance increased from 24 percent in
      1997 to 28 percent in 2004 and then rose dramatically, to 49 percent in 2006.
      Rural and urban levels of insurance coverage became more similar, reflecting a
      dramatic upswing in coverage in rural areas that is likely to have benefited
      millions of rural Chinese. At the same time, the analysis suggests that health
      insurance reimbursement rates to consumers for inpatient care might have declined
      in rural villages. Because reimbursement and other insurance characteristics
      affect health care use, future efforts to reduce rural-urban disparities should
      address the quality of health insurance and the level of reimbursement in
      addition to coverage rates.

PMID- 22147872
TI  - An experiment in payment reform for doctors in rural China reduced some
      unnecessary care but did not lower total costs.
AB  - Inefficiency and low quality of health services are common in many developing
      countries. To mitigate these problems, we conducted an experiment in rural China
      in which we changed the existing fee-for-service method of paying village doctors
      to a mixed payment method that included a salary plus a bonus based on
      performance. The new payment method also removed a feature that previously
      allowed doctors to purchase medications to prescribe to patients and earn a
      markup on each prescription. Changing these payment incentives reduced spending
      at the village level, curbed unnecessary care for healthier patients, and also
      decreased the prescribing of unnecessary drugs. However, other features of the
      arrangement encouraged doctors to refer sicker patients to township and county
      facilities, where costs were higher. As a result, total health care spending was
      not significantly reduced. The findings underscore that policy makers should
      design payment methods carefully to both contain costs and improve quality.

PMID- 22147873
TI  - An MS patient loses trust when she finds out her doctor is paid by drug
      companies.

PMID- 22147876
TI  - High physician fees and high health spending.

PMID- 22147878
TI  - Drivers of high US health care costs.

PMID- 22147879
TI  - 'Almost nonexistent' dental care on Indian reservations.

PMID- 22147880
TI  - Reducing existing discrimination.

PMID- 22147881
TI  - Policy implications of adjusting randomized trial data for economic evaluations:
      a demonstration from the ASCUS-LSIL Triage Study.
AB  - BACKGROUND: Although the randomized controlled trial (RCT) is widely considered
      the most reliable method for evaluation of health care interventions, challenges
      to both internal and external validity exist. Thus, the efficacy of an
      intervention in a trial setting does not necessarily represent the real-world
      performance that decision makers seek to inform comparative effectiveness studies
      and economic evaluations. METHODS: Using data from the ASCUS-LSIL Triage Study
      (ALTS), we performed a simplified economic evaluation of age-based management
      strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) among
      women who were referred to the study with low-grade squamous intraepithelial
      lesions (LSIL). We used data from the trial itself to adjust for 1) potential
      lead time bias and random error that led to variation in the observed prevalence
      of CIN3 by study arm and 2) potential ascertainment bias among providers in the
      most aggressive management arm. RESULTS: We found that using unadjusted RCT data
      may result in counterintuitive cost-effectiveness results when random error
      and/or bias are present. Following adjustment, the rank order of management
      strategies changed for 2 of the 3 age groups we considered. CONCLUSIONS: Decision
      analysts need to examine study design, available trial data, and cost
      effectiveness results closely in order to detect evidence of potential bias.
      Adjustment for random error and bias in RCTs may yield different policy
      conclusions relative to unadjusted trial data.

PMID- 22147882
TI  - A percutaneous coronary intervention lab in every hospital?
AB  - BACKGROUND: In 2001, 1176 US hospitals were capable of performing primary
      percutaneous coronary intervention (PCI), and 79% of the population lived within
      60-minute ground transport of these hospitals. We compared these estimates with
      data from 2006 to explore how hospital PCI capability and population access have
      changed over time. METHODS AND RESULTS: We estimated the proportion of the
      population 18 years of age or older, living in 2006 within a 60-minute drive of a
      PCI-capable hospital, and we compared our estimate with a previously published
      report on 2001 data. Over the 5-year period, the number of PCI-capable hospitals
      grew from 1176 to 1695 hospitals, a relative increase of 44%; access to the
      procedure grew from 79.0% to 79.9% of the population, a relative increase of 1%.
      CONCLUSIONS: Our data indicate a large increase in the number of hospitals
      capable of performing PCI from 2001 to 2006, but this increase was not associated
      with an appreciable change in the proportion of the population with access to the
      procedure. In the future, more attention is needed on changes in PCI capacity
      over time and on the effects of these changes on outcomes of interest such as
      service utilization, expenditures, patient outcomes, and population health.

PMID- 22147883
TI  - Retrospective description and analysis of consecutive catheterization laboratory
      ST-segment elevation myocardial infarction activations with proposal, rationale,
      and use of a new classification scheme.
AB  - BACKGROUND: Rapid activation of a cardiac catheterization laboratory (CCL) has
      reduced door-to-balloon times in ST-segment elevation myocardial infarction
      (STEMI), leading to lower mortality. This process is accelerated with prehospital
      electrocardiography and notification. False activations of the CCL occur at an
      unknown rate and have been poorly described. METHODS AND RESULTS: We analyzed 345
      consecutive CCL activations for suspected STEMI over 18 months (March 2009-August
      2010). We retrospectively reviewed the ECGs that prompted activation, as well as
      the clinical course and final diagnoses. Among all CCL activations, STEMI was not
      confirmed in 28%. On review, 301 (87.2%) had appropriate ECG criteria for
      activation. However, even among the ECG-appropriate patients, only 247 (82%) had
      a final diagnosis of STEMI. The inclusion of clinical characteristics did not
      improve the ability to identify patients with STEMI. Activations were modestly
      more accurate when made by emergency department physicians than by emergency
      medical service personnel, but door-to-balloon time was noticeably shorter when
      emergency medical service personnel requested prehospital activation.
      CONCLUSIONS: If all CCL activations are considered, the occurrence of false
      activations is surprisingly high. Although still the gold standard for diagnosis,
      these data reveal the inherent limitations of clinical evaluation and the ECG in
      identifying patients with STEMI. Within our retrospective review, we used a 2
      tiered classification for STEMI activations based on ECG appropriateness and
      final clinical diagnosis to give a complete picture of false activations and
      assist in quality improvement.

PMID- 22147884
TI  - Introduction of the Tools for Economic Analysis of Patient Management
      Interventions in Heart Failure Costing Tool: a user-friendly spreadsheet program
      to estimate costs of providing patient-centered interventions.
AB  - BACKGROUND: Patient-centered health care interventions, such as heart failure
      disease management programs, are under increasing pressure to demonstrate good
      value. Variability in costing methods and assumptions in economic evaluations of
      such interventions limit the comparability of cost estimates across studies.
      Valid cost estimation is critical to conducting economic evaluations and for
      program budgeting and reimbursement negotiations. METHODS AND RESULTS: Using
      sound economic principles, we developed the Tools for Economic Analysis of
      Patient Management Interventions in Heart Failure (TEAM-HF) Costing Tool, a
      spreadsheet program that can be used by researchers and health care managers to
      systematically generate cost estimates for economic evaluations and to inform
      budgetary decisions. The tool guides users on data collection and cost assignment
      for associated personnel, facilities, equipment, supplies, patient incentives,
      miscellaneous items, and start-up activities. The tool generates estimates of
      total program costs, cost per patient, and cost per week and presents results
      using both standardized and customized unit costs for side-by-side comparisons.
      Results from pilot testing indicated that the tool was well-formatted, easy to
      use, and followed a logical order. Cost estimates of a 12-week exercise training
      program in patients with heart failure were generated with the costing tool and
      were found to be consistent with estimates published in a recent study.
      CONCLUSIONS: The TEAM-HF Costing Tool could prove to be a valuable resource for
      researchers and health care managers to generate comprehensive cost estimates of
      patient-centered interventions in heart failure or other conditions for
      conducting high-quality economic evaluations and making well-informed health care
      management decisions.

PMID- 22147885
TI  - Clopidogrel use and early outcomes among older patients receiving a drug-eluting
      coronary artery stent.
AB  - BACKGROUND: Clopidogrel use after drug-eluting stent (DES) coronary artery
      implantation is essential for the prevention of early in-stent thrombosis, but
      clopidogrel use among older DES recipients has not been widely studied. We sought
      to identify characteristics associated with failure to fill a clopidogrel
      prescription and to examine the relationship between a clopidogrel prescription
      fill and hospitalization for acute myocardial infarction (AMI) or death. METHODS
      AND RESULTS: This study was a retrospective analysis of administrative data (20%
      sample) of 15 996 Medicare Part D enrollees who received a DES in 2006 to 2007.
      We modeled the adjusted probability and odds of clopidogrel prescription fill
      within 7 and 90 days of discharge and its association with AMI hospitalization or
      death. Of the study sample, 19.7% did not fill a clopidogrel prescription within
      7 days of discharge, falling to 13.3% by day 90. The adjusted probability of
      filling a clopidogrel prescription within 7 or 90 days of discharge was lower for
      patients with dementia (20.2% less likely; 95% CI, 10.4%-30.1%), depression
      (10.7% less likely; 95% CI, 6.9%-14.5%), age >84 years compared to age 65 to 69
      years (10.6% less likely; 95% CI, 8.6%-12.7%), black race (6.6% less likely; 95%
      CI, 4.2%-9.0%), intermediate levels of medication cost share (5.2% less likely;
      95% CI, 2.9%-7.6%), and female sex (3.3% less likely; 95% CI, 2.1%-4.5%). It was
      higher for patients initially hospitalized for an AMI (12.5% more likely; 95% CI,
      11.3%-13.6%). Failure to fill a clopidogrel prescription within 7 days of
      discharge was associated with a higher adjusted odds ratio of death during days 8
      to 90 (2.44; 95% CI, 1.76-3.38) but was not associated with an increased risk of
      hospitalization for AMI. CONCLUSIONS: One in 5 patients failed to fill a
      prescription for clopidogrel at 7 days after DES placement, and 1 in 7 failed to
      do so by 3 months. Individual characteristics available at the time of hospital
      discharge were associated with a clopidogrel prescription fill. Those
      characteristics most strongly associated with nonadherence, including age >84
      years, not having an AMI, depression, and dementia, may guide clinicians and
      health systems seeking to target this high-risk population and improve health
      outcomes after percutaneous coronary intervention.

PMID- 22147886
TI  - Variation in the use of lower extremity vascular procedures for critical limb
      ischemia.
AB  - BACKGROUND: Many believe that variation in vascular practice may affect limb
      salvage rates in patients with severe peripheral arterial disease. However, the
      extent of variation in procedural vascular care obtained by patients with
      critical limb ischemia (CLI) remains unknown. METHODS AND RESULTS: By using
      Medicare 2003 to 2006 data, we identified all patients with CLI who underwent
      major lower extremity amputation in the 306 hospital referral regions described
      in the Dartmouth Atlas of Healthcare. For each patient, we studied the use of
      lower extremity vascular procedures (open surgery or endovascular intervention)
      in the year before amputation. Our main outcome measure was the intensity of
      vascular care, defined as the proportion of patients in the hospital referral
      region undergoing a vascular procedure in the year before amputation. Overall,
      20,464 patients with CLI underwent major lower extremity amputations during the
      study period, and collectively underwent 25,800 vascular procedures in the year
      before undergoing amputation. However, these procedures were not distributed
      evenly: 54% of patients had no vascular procedures performed in the year before
      amputation, 14% underwent 1 vascular procedure, and 32% underwent >1 vascular
      procedure. In the regions in the lowest quintile of vascular intensity, vascular
      procedures were performed in 32% of patients. Conversely, in the regions in the
      highest quintile of vascular intensity, revascularization was performed in 58% of
      patients in the year before amputation (P<0.0001). In analyses accounting for
      differences in age, sex, race, and comorbidities, patients in high-intensity
      regions were 2.4 times as likely to undergo revascularization in the year before
      amputation than patients in low-intensity regions (adjusted odds ratio, 2.4; 95%
      CI, 2.1-2.6; P<0.001). CONCLUSIONS: Significant variation exists in the intensity
      of vascular care provided to patients in the year before major amputation. In
      some regions, patients receive intensive care, whereas in other regions, far less
      vascular care is provided. Future work is needed to determine the association
      between intensity of vascular care and limb salvage.

PMID- 22147888
TI  - Estimating and reporting on the quality of inpatient stroke care by Veterans
      Health Administration Medical Centers.
AB  - BACKGROUND: Reporting of quality indicators (QIs) in Veterans Health
      Administration Medical Centers is complicated by estimation error caused by small
      numbers of eligible patients per facility. We applied multilevel modeling and
      empirical Bayes (EB) estimation in addressing this issue in performance reporting
      of stroke care quality in the Medical Centers. METHODS AND RESULTS: We studied a
      retrospective cohort of 3812 veterans admitted to 106 Medical Centers with
      ischemic stroke during fiscal year 2007. The median number of study patients per
      facility was 34 (range, 12-105). Inpatient stroke care quality was measured with
      13 evidence-based QIs. Eligible patients could either pass or fail each
      indicator. Multilevel modeling of a patient's pass/fail on individual QIs was
      used to produce facility-level EB-estimated QI pass rates and confidence
      intervals. The EB estimation reduced interfacility variation in QI rates. Small
      facilities and those with exceptionally high or low rates were most affected. We
      recommended 8 of the 13 QIs for performance reporting: dysphagia screening,
      National Institutes of Health Stroke Scale documentation, early ambulation, fall
      risk assessment, pressure ulcer risk assessment, Functional Independence Measure
      documentation, lipid management, and deep vein thrombosis prophylaxis. These QIs
      displayed sufficient variation across facilities, had room for improvement, and
      identified sites with performance that was significantly above or below the
      population average. The remaining 5 QIs were not recommended because of too few
      eligible patients or high pass rates with little variation. CONCLUSIONS:
      Considerations of statistical uncertainty should inform the choice of QIs and
      their application to performance reporting.

PMID- 22147887
TI  - Use and effectiveness of intra-aortic balloon pumps among patients undergoing
      high risk percutaneous coronary intervention: insights from the National
      Cardiovascular Data Registry.
AB  - BACKGROUND: Intra-aortic balloon pumps (IABP) frequently are used to provide
      hemodynamic support during high risk percutaneous coronary intervention (PCI),
      but clinical evidence to support their use is mixed. We examined hospital
      variation in IABP use among high risk PCI patients, and determined the
      association of IABP use on mortality in this population. METHODS AND RESULTS: We
      analyzed data submitted to the CathPCI Registry between January 2005 and December
      2007. High risk PCI was defined as having at least 1 of the following features:
      unprotected left main artery as the target vessel, cardiogenic shock, severely
      depressed left ventricular function, or ST segment elevation myocardial
      infarction. Hospitals were categorized into quartiles by their proportional use
      of IABP. We examined differences in in-hospital mortality across hospital
      quartiles using a hierarchical logistic regression model to adjust for
      differences in patient and hospital characteristics across hospital quartiles of
      IABP use. IABPs were used in 18,990 (10.5%) of 181,599 high risk PCIs.
      Proportional use of IABP varied significantly across hospital quartiles: Q1, 0.0
      to 6.5%; Q2, 6.6 to 9.2%; Q3, 9.3 to 14.1%; Q4, 14.2 to 40.0%. In multivariable
      analysis, after adjustment for differences in patient and hospital
      characteristics, in-hospital mortality was comparable across quartiles of
      hospital IABP usage (Q1, Ref; Q2, odds ratio 1.11, 95% CI 0.99-1.24; Q3, OR 1.03,
      95% CI 0.92-1.15; Q4, OR 1.06, 95% CI 0.94-1.18). CONCLUSIONS: IABP use varied
      significantly across hospitals for high risk PCI. However, this variation in IABP
      use was not associated with differences in in-hospital mortality.

PMID- 22147889
TI  - Duplications of BHLHA9 are associated with ectrodactyly and tibia hemimelia
      inherited in non-Mendelian fashion.
AB  - BACKGROUND: Split-hand/foot malformation (SHFM)-also known as ectrodactyly-is a
      congenital disorder characterised by severe malformations of the distal limbs
      affecting the central rays of hands and/or feet. A distinct entity termed SHFLD
      presents with SHFM and long bone deficiency. Mouse models suggest that a defect
      of the central apical ectodermal ridge leads to the phenotype. Although six
      different loci/mutations (SHFM1-6) have been associated with SHFM, the underlying
      cause in a large number of cases is still unresolved. METHODS: High resolution
      array comparative genomic hybridisation (CGH) was performed in patients with
      SHFLD to detect copy number changes. Candidate genes were further evaluated for
      expression and function during limb development by whole mount in situ
      hybridisation and morpholino knock-down experiments. RESULTS: Array CGH showed
      microduplications on chromosome 17p13.3, a locus previously associated with
      SHFLD. Detailed analysis of 17 families revealed that this copy number variation
      serves as a susceptibility factor for a highly variable phenotype with reduced
      penetrance, particularly in females. Compared to other known causes for SHFLD 17p
      duplications appear to be the most frequent cause of SHFLD. A ~11.8 kb minimal
      critical region was identified encompassing a single gene, BHLHA9, a putative
      basic loop helix transcription factor. Whole mount in situ hybridisation showed
      expression restricted to the limb bud mesenchyme underlying the apical ectodermal
      ridge in mouse and zebrafish embryos. Knock down of bhlha9 in zebrafish resulted
      in shortening of the pectoral fins. CONCLUSIONS: Genomic duplications
      encompassing BHLHA9 are associated with SHFLD and non-Mendelian inheritance
      characterised by a high degree of non-penetrance with sex bias. Knock-down of
      bhlha9 in zebrafish causes severe reduction defects of the pectoral fin,
      indicating a role for this gene in limb development.

PMID- 22147890
TI  - Evidence-based focused review of management of hyperviscosity syndrome.

PMID- 22147891
TI  - TLR3 essentially promotes protective class I-restricted memory CD8+ T-cell
      responses to Aspergillus fumigatus in hematopoietic transplanted patients.
AB  - Aspergillus fumigatus is a model fungal pathogen and a common cause of severe
      infections and diseases. CD8+ T cells are present in the human and murine T-cell
      repertoire to the fungus. However, CD8+ T-cell function in infection and the
      molecular mechanisms that control their priming and differentiation into effector
      and memory cells in vivo remain elusive. In the present study, we report that
      both CD4+ and CD8+ T cells mediate protective memory responses to the fungus
      contingent on the nature of the fungal vaccine. Mechanistically, class I MHC
      restricted, CD8+ memory T cells were activated through TLR3 sensing of fungal RNA
      by cross-presenting dendritic cells. Genetic deficiency of TLR3 was associated
      with susceptibility to aspergillosis and concomitant failure to activate memory
      protective CD8+ T cells both in mice and in patients receiving stem-cell
      transplantations. Therefore, TLR3 essentially promotes antifungal memory CD8+ T
      cell responses and its deficiency is a novel susceptibility factor for
      aspergillosis in high-risk patients.

PMID- 22147892
TI  - Progress in Hodgkin lymphoma: a population-based study on patients diagnosed in
      Sweden from 1973-2009.
AB  - In recent decades, attention has focused on reducing long-term, treatment-related
      morbidity and mortality in Hodgkin lymphoma (HL). In the present study, we looked
      for trends in relative survival for all patients diagnosed with HL in Sweden from
      1973-2009 (N = 6949; 3985 men and 2964 women; median age, 45 years) and followed
      up for death until the end of 2010. Patients were categorized into 6 age groups
      and 5 calendar periods (1973-1979, 1980-1986, 1987-1994, 1994-2000, and 2001
      2009). Relative survival improved in all age groups, with the greatest
      improvement in patients 51-65 years of age (P < .0005). A plateau in relative
      survival was observed in patients below 65 years of age during the last calendar
      period, suggesting a reduced long-term, treatment-related mortality. The 10-year
      relative survival for patients diagnosed in 2000-2009 was 0.95, 0.96, 0.93, 0.80,
      and 0.44 for the age groups 0-18, 19-35, 36-50, 51-65, and 66-80, respectively.
      Therefore, despite progress, age at diagnosis remains an important prognostic
      factor (P < .0005). Advances in therapy for patients with limited and advanced
      stage HL have contributed to an increasing cure rate. In addition, our findings
      support that long-term mortality of HL therapy has decreased. Elderly HL patients
      still do poorly, and targeted treatment options associated with fewer side
      effects will advance the clinical HL field.

PMID- 22147893
TI  - High-dose melphalan and peripheral blood stem cell transplantation for light
      chain amyloidosis with cardiac involvement.
AB  - High-dose melphalan (HDM) plus stem cell transplantation is an effective
      treatment for light-chain amyloidosis (AL), but is associated with high treatment
      related mortality in patients with cardiac involvement. We studied 187 patients
      with cardiac involvement with AL who underwent HDM between 1996 and 2008. The
      median age was 57 years and the median time from diagnosis to HDM was 3.6 months.
      Half of the patients received reduced-dose melphalan (100-160 mg/m(2)). The
      median overall survival (OS) was 66 months, 54 months from diagnosis and HDM,
      respectively, and 91 patients (49%) were alive at the last follow-up 52 months
      (median) from HDM. Thirty patients (16%) died within 100 days of transplantation;
      only low serum albumin predicted early deaths. Overall, hematologic response (HR)
      and cardiac responses were seen in 66% and 41% of patients, respectively. The
      median OS for patients with and without HR was not reached and 22 months,
      respectively (P < .01); and for those with any decrease and no decrease in N
      terminal-pro-brain natriuretic peptide was not reached and 26 months,
      respectively (P < .01). In multivariate analysis of baseline factors, only
      reduced-dose melphalan predicted shorter OS. HDM is feasible in patients with
      cardiac amyloidosis, and achievement of HR and organ response is associated with
      improved survival.

PMID- 22147894
TI  - Global gene expression profiling in mouse plasma cell tumor precursor and
      bystander cells reveals potential intervention targets for plasma cell neoplasia.
AB  - Tumor progression usually proceeds through several sequential stages, any of
      which could be targets for interrupting the progression process if one understood
      these steps at the molecular level. We extracted nascent plasma cell tumor (PCT)
      cells from within inflammatory oil granulomas (OG) isolated from IP pristane
      injected BALB/c.iMyc(EMU) mice at 5 different time points during tumor
      progression. We used laser capture microdissection to collect incipient PCT cells
      and analyzed their global gene expression on Affymetrix Mouse Genome 430A
      microarrays. Two independent studies were performed with different sets of mice.
      Analysis of the expression data used ANOVA and Bayesian estimation of temporal
      regulation. Genetic pathway analysis was performed using MetaCore (GeneGo) and
      IPA (Ingenuity). The gene expression profiles of PCT samples and those of
      undissected OG samples from adjacent sections showed that different genes and
      pathways were mobilized in the tumor cells during tumor progression, compared
      with their stroma. Our analysis implicated several genetic pathways in PCT
      progression, including biphasic (up- and then down-regulation) of the
      Spp1/osteopontin-dependent network and up-regulation of mRNA translation/protein
      synthesis. The latter led to a biologic validation study that showed that the
      AMPK-activating diabetes drug, metformin, was a potent specific PCT inhibitor in
      vitro.

PMID- 22147895
TI  - Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC
      syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic
      vasculature.
AB  - Recent work has established that heterozygous germline GATA2 mutations predispose
      carriers to familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML),
      "MonoMAC" syndrome, and DCML deficiency. Here, we describe a previously
      unreported MDS family carrying a missense GATA2 mutation (p.Thr354Met), one
      patient with MDS/AML carrying a frameshift GATA2 mutation (p.Leu332Thrfs*53),
      another with MDS harboring a GATA2 splice site mutation, and 3 patients
      exhibiting MDS or MDS/AML who have large deletions encompassing the GATA2 locus.
      Intriguingly, 2 MDS/AML or "MonoMAC" syndrome patients with GATA2 deletions and
      one with a frameshift mutation also have primary lymphedema. Primary lymphedema
      occurs as a result of aberrations in the development and/or function of lymphatic
      vessels, spurring us to investigate whether GATA2 plays a role in the lymphatic
      vasculature. We demonstrate here that GATA2 protein is present at high levels in
      lymphatic vessel valves and that GATA2 controls the expression of genes important
      for programming lymphatic valve development. Our data expand the phenotypes
      associated with germline GATA2 mutations to include predisposition to primary
      lymphedema and suggest that complete haploinsufficiency or loss of function of
      GATA2, rather than missense mutations, is the key predisposing factor for
      lymphedema onset. Moreover, we reveal a crucial role for GATA2 in lymphatic
      vascular development.

PMID- 22147896
TI  - An intrinsic BM hematopoietic niche occupancy defect of HSC in scid mice
      facilitates exogenous HSC engraftment.
AB  - Although scid mice have been widely used for human HSC engraftment studies, the
      function of HSCs of scid mice has not been characterized. We hypothesized that
      the DNA repair defect of scid mice results in a stem cell defect that facilitates
      HSC engraftment. scid BM cells showed severely impaired repopulation potentials
      in the competitive repopulation assay. To assess the BM hematopoietic niche
      occupancy ability of scid HSC, WT BM cells were transplanted into scid mice
      without any conditioning and observed to achieve long-term engraftment.
      Furthermore, the defects of scid HSCs are independent of their inability to
      perform lymphopoiesis because a similar defect in hematopoietic niche occupancy
      was not observed with Rag1(-/-) recipients. These results demonstrate that scid
      HSCs are impaired in maintenance within the niche, which may explain the nature
      of the conducive marrow niche environment of scid mice for xenotransplantation.

PMID- 22147897
TI  - Comparative incidence of a first thrombotic event in purely obstetric
      antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study.
AB  - The incidence of thrombosis in the purely obstetric form of antiphospholipid
      syndrome is uncertain. We performed a 10-year observational study of 1592
      nonthrombotic women who had experienced 3 consecutive spontaneous abortions
      before the 10th week of gestation or 1 fetal death at or beyond the 10th week of
      gestation. We compared the frequencies of thrombotic events among women positive
      for antiphospholipid Abs (n = 517), women carrying the F5 6025 or F2 rs1799963
      polymorphism (n = 279), and women with negative thrombophilia screening results
      (n = 796). The annual rates of deep vein thrombosis (1.46%; range, 1.15%-1.82%),
      pulmonary embolism (0.43%; range, 0.26%-0.66%), superficial vein thrombosis
      (0.44%; range, 0.28%-0.68%), and cerebrovascular events (0.32%; range, 0.18%
      0.53%) were significantly higher in aPLAbs women than in the other groups despite
      low-dose aspirin primary prophylaxis. Women carrying 1 of the 2 polymorphisms did
      not experience more thrombotic events than women who screened negative for
      thrombophilia. Lupus anticoagulant was a risk factor for unprovoked proximal and
      distal deep and superficial vein thrombosis and women in the upper quartile of
      lupus anticoagulant activity had the highest risk. Despite data suggesting that
      aPLAbs may induce pregnancy loss through nonthrombotic mechanisms, women with
      purely obstetric antiphospholipid syndrome are at risk for thrombotic
      complications.

PMID- 22147900
TI  - Influence of access site selection on PCI-related adverse events in patients with
      STEMI: meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: A meta-analysis of all randomised controlled studies that compare
      outcomes of transradial versus the transfemoral route to better define best
      practice in patients with ST elevation myocardial infarction (STEMI). DESIGN: A
      Medline and Embase search was conducted using the search terms 'transradial,'
      'radial', 'STEMI', 'myocardial' and 'infarction'. SETTING: Randomised controlled
      studies that compare outcomes of transradial versus the transfemoral route.
      PATIENTS: A total of nine studies were identified that consisted of 2977 patients
      with STEMI. Interventions Studies that compare outcomes of transradial versus the
      transfemoral route. MAIN OUTCOME MEASURES: The primary clinical outcomes of
      interest were (1) mortality; (2) major adverse cardiac events (MACE); (3) major
      bleeding and (4) access site complications. RESULTS: Transradial PCI was
      associated with a reduction in mortality (OR 0.53, 95% CI 0.33 to 0.84; p=0.008),
      MACE (OR 0.62, 95% CI 0.43 to 0.90; p=0.012), major bleeding events (OR 0.63, 95%
      CI 0.35-1.12; p=0.12) and access site complications (OR 0.30, 95% CI 0.19 to
      0.48; p<0.0001) compared with procedures performed through the femoral route.
      CONCLUSIONS: This meta-analysis demonstrates a significant reduction in
      mortality, MACE and major access site complications associated with the
      transradial access site in STEMI. The meta-analysis supports the preferential use
      of radial access for STEMI PCI.

PMID- 22147901
TI  - Radial versus femoral access for primary percutaneous coronary intervention: is
      there a preferred route to the heart?

PMID- 22147898
TI  - Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated
      sickle red cell adhesion to endothelium.
AB  - The core pathology of sickle cell disease (SCD) starts with the erythrocyte
      (RBC). Aberration in MAPK/ERK1/2 signaling, which can regulate cell adhesion,
      occurs in diverse pathologies. Because RBCs contain abundant ERK1/2, we predicted
      that ERK1/2 is functional in sickle (SS) RBCs and promotes adherence, a hallmark
      of SCD. ERK1/2 remained active in SS but not normal RBCs. beta(2)-adrenergic
      receptor stimulation by epinephrine can enhance ERK1/2 activity only in SS RBCs
      via PKA- and tyrosine kinase p72(syk)-dependent pathways. ERK signaling is
      implicated in RBC ICAM-4 phosphorylation, promoting SS RBC adhesion to the
      endothelium. SS RBC adhesion and phosphorylation of both ERK and ICAM-4 all
      decreased with continued cell exposure to epinephrine, implying that activation
      of ICAM-4-mediated SS RBC adhesion is temporally associated with ERK1/2
      activation. Furthermore, recombinant ERK2 phosphorylated alpha- and beta-adducins
      and dematin at the ERK consensus motif. Cytoskeletal protein 4.1 also showed
      dynamic phosphorylation but not at the ERK consensus motif. These results
      demonstrate that ERK activation induces phosphorylation of cytoskeletal proteins
      and the adhesion molecule ICAM-4, promoting SS RBC adhesion to the endothelium.
      Thus, blocking RBC ERK1/2 activation, such as that promoted by catecholamine
      stress hormones, could ameliorate SCD pathophysiology.

PMID- 22147902
TI  - Is cardiac resynchronisation therapy better than right ventricular pacing after
      atrioventricular junction ablation for medically refractory atrial fibrillation?

PMID- 22147903
TI  - Clinical implications of electrocardiographic left ventricular strain and
      hypertrophy in asymptomatic patients with aortic stenosis: the Simvastatin and
      Ezetimibe in Aortic Stenosis study.
AB  - BACKGROUND: The prognostic impact of ECG left ventricular strain and left
      ventricular hypertrophy (LVH) in asymptomatic aortic stenosis is not well
      described. METHODS AND RESULTS: Data were obtained in asymptomatic patients
      randomized to simvastatin/ezetimibe combination versus placebo in the Simvastatin
      and Ezetimibe in Aortic Stenosis (SEAS) study. Primary end point was the first of
      myocardial infarction, nonhemorrhagic stroke, heart failure, aortic valve
      replacement, or cardiovascular death. The predictive value of ECG left
      ventricular strain (defined as T-wave inversion in leads V(4) through V(6)) and
      LVH, assessed by Sokolow-Lyon voltage criteria (R(V5-6)+S(V1) >=35 mV) and
      Cornell voltage-duration criteria {[RaVL+S(V3)+(6 mV in women)]*QRS duration
      >=2440 mV . ms}, was evaluated by adjustment for other prognostic covariates. A
      total of 1533 patients were followed for 4.3+/-0.8 years (6592 patient-years of
      follow-up), and 627 cardiovascular events occurred. ECG strain was present in 340
      patients (23.6%), with LVH by Sokolow-Lyon voltage in 260 (17.1%) and by Cornell
      voltage-duration product in 220 (14.6%). In multivariable analyses, ECG left
      ventricular strain was associated with 3.1-fold higher risk of in-study
      myocardial infarction (95% confidence interval, 1.4-6.8; P=0.004). Similarly, ECG
      LVH by both criteria predicted, compared with no ECG LVH, 5.8-fold higher risk of
      heart failure (95% confidence interval, 2.0-16.8), 2.0-fold higher risk of aortic
      valve replacement (95% confidence interval, 1.3-3.1; both P=0.001), and 2.5-fold
      higher risk of a combined end point of myocardial infarction, heart failure, or
      cardiovascular death (95% confidence interval, 1.3-4.9; P=0.008). CONCLUSIONS:
      ECG left ventricular strain and LVH were independently predictive of poor
      prognosis in patients with asymptomatic aortic stenosis. CLINICAL TRIAL
      REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

PMID- 22147904
TI  - Rates of cardiac catheterization cancelation for ST-segment elevation myocardial
      infarction after activation by emergency medical services or emergency
      physicians: results from the North Carolina Catheterization Laboratory Activation
      Registry.
AB  - BACKGROUND: For patients with an acute ST-segment elevation myocardial
      infarction, cardiac catheterization laboratory (CCL) activation by emergency
      medical technicians or emergency physicians has been shown to substantially
      reduce treatment times. One drawback to this approach involves overtriage,
      whereby CCL staffs are activated for patients who ultimately do not require
      emergent coronary angiography or for patients who undergo angiography but are not
      found to have coronary artery occlusion. METHODS AND RESULTS: We examined CCL
      activation at 14 primary angioplasty hospitals to determine the course of
      management, including the rate of inappropriate activation. Among 3973
      activations (29% by emergency medical technicians, 71% by emergency physicians)
      between December 2008 and December 2009, appropriate CCL activations occurred for
      3377 patients (85%), with 2598 patients (76.9% of appropriate activations)
      receiving primary percutaneous coronary intervention. Reasons for inappropriate
      activations (596 patients; 15%) included ECG reinterpretations (427 patients;
      72%) or the fact that the patient was not a CCL candidate (169 patients; 28%).
      The rate of cancellation because of reinterpretation of emergency medical
      technicians' ECG (6% of all activations) was more common than for cancellation
      because of reinterpretation of emergency physicians' ECG (4.6%). CONCLUSIONS:
      This represents the first report of the rates of CCL cancellation for ST-segment
      elevation myocardial infarction system activation by emergency medical
      technicians and emergency physicians in a large group of hospitals organized
      within a statewide program. The high rate of coronary intervention and relatively
      low rate of inappropriate activation suggest that systematic CCL activation by
      emergency personnel on a broad scale is feasible and accurate, and these rates
      set a benchmark for ST-segment elevation myocardial infarction systems.

PMID- 22147905
TI  - Comprehensive use of cardiopulmonary exercise testing identifies adults with
      congenital heart disease at increased mortality risk in the medium term.
AB  - BACKGROUND: Parameters of cardiopulmonary exercise testing were recently
      identified as strong predictors of mortality in adults with congenital heart
      disease. We hypothesized that combinations of cardiopulmonary exercise testing
      parameters may provide optimal prognostic information on midterm survival in this
      population. METHODS AND RESULTS: A total of 1375 consecutive adult patients with
      congenital heart disease (age, 33+/-13 years) underwent cardiopulmonary exercise
      testing at a single center over a period of 10 years. Peak oxygen consumption
      (peak V(O(2))), ventilation per unit of carbon dioxide production (V(E)/V(O(2))
      slope), and heart rate reserve were measured. During a median follow-up of 5.8
      years, 117 patients died. Peak V(O(2)), heart rate reserve, and V(E)/V(O(2))
      slope were related to midterm survival in adult patients with congenital heart
      disease. Risk of death increased with lower peak V(O(2)) and heart rate reserve.
      A higher V(E)/V(O(2)) slope was also related to increased risk of death in
      noncyanotic patients, whereas the V(E)/V(O(2)) slope was not predictive of
      mortality in cyanotic patients. The combination of peak V(O(2)) and heart rate
      reserve provided the greatest predictive information after adjustment for
      clinical parameters such as negative chronotropic agents, age, and presence of
      cyanosis. However, the incremental value of these exercise parameters was reduced
      in patients with peak respiratory exchange ratio <1.0. CONCLUSIONS:
      Cardiopulmonary exercise testing provides strong prognostic information in adult
      patients with congenital heart disease. Prognostication should be approached
      differently, depending on the presence of cyanosis, use of rate-lowering
      medications, and achieved level of exercise. We provide 5-year survival prospects
      based on cardiopulmonary exercise testing parameters in this growing population.

PMID- 22147906
TI  - Cardiopulmonary exercise testing in adults with congenital heart disease: can we
      prognosticate and improve prognosis?

PMID- 22147908
TI  - Patterning the artery wall by lateral induction of Notch signaling.

PMID- 22147907
TI  - Notch activation of Jagged1 contributes to the assembly of the arterial wall.
AB  - BACKGROUND: Notch signaling in vascular smooth muscle precursors is required for
      smooth muscle differentiation. Jagged1 expression on endothelium activates Notch
      in vascular smooth muscle precursors including those of neural crest origin to
      initiate the formation of a smooth muscle layer in a maturing blood vessel.
      METHODS AND RESULTS: Here, we show that Jagged1 is a direct Notch target in
      smooth muscle, resulting in a positive feedback loop and lateral induction that
      propagates a wave of smooth muscle differentiation during aortic arch artery
      development. In vivo, we show that Notch inhibition in cardiac neural crest
      impairs Jagged1 messenger RNA expression and results in deficient smooth muscle
      differentiation and resultant aortic arch artery defects. Ex vivo, Jagged1 ligand
      activates Notch in neural crest explants and results in activation of Jagged1
      messenger RNA, a response that is blocked by Notch inhibition. We examine 15
      evolutionary conserved regions within the Jagged1 genomic locus and identify a
      single Notch response element within the second intron. This element contains a
      functional Rbp-J binding site demonstrated by luciferase reporter and chromatin
      immunoprecipitation assays and is sufficient to recapitulate aortic arch artery
      expression of Jagged1 in transgenic mice. Loss of Jagged1 in neural crest impairs
      vascular smooth muscle differentiation and results in aortic arch artery defects.
      CONCLUSIONS: Taken together, these results provide a mechanism for lateral
      induction that allows for a multilayered smooth muscle wall to form around a
      nascent arterial endothelial tube and identify Jagged1 as a direct Notch target.

PMID- 22147909
TI  - Association between bisphosphonate use and implant survival after primary total
      arthroplasty of the knee or hip: population based retrospective cohort study.
AB  - OBJECTIVES: To test whether bisphosphonate use is related to improved implant
      survival after total arthroplasty of the knee or hip. DESIGN: Population based
      retrospective cohort study. SETTING: Primary care data from the United Kingdom.
      PARTICIPANTS: All patients undergoing primary total arthroplasty of the knee (n =
      18,726) or hip (n = 23,269) in 1986-2006 within the United Kingdom's General
      Practice Research Database. We excluded patients with a history of hip fracture
      before surgery or rheumatoid arthritis, and individuals younger than 40 years at
      surgery. INTERVENTION: Bisphosphonate users were classified as patients with at
      least six prescriptions of bisphosphonates or at least six months of prescribed
      bisphosphonate treatment with more than 80% adherence before revision surgery.
      OUTCOME MEASURES: Revision arthroplasties occurring after surgery, identified by
      READ and OXMIS codes. Parametric survival models were used to determine effects
      on implant survival with propensity score adjustment to account for confounding
      by indication. Results Of 41 995 patients undergoing primary hip or knee
      arthroplasty, we identified 1912 bisphosphonate users, who had a lower rate of
      revision at five years than non-users (0.93% (95% confidence interval 0.52% to
      1.68%) v 1.96% (1.80% to 2.14%)). Implant survival was significantly longer in
      bisphosphonate users than in non-users in propensity adjusted models (hazard
      ratio 0.54 (0.29 to 0.99); P = 0.047) and had an almost twofold increase in time
      to revision after hip or knee arthroplasty (time ratio 1.96 (1.01 to 3.82)).
      Assuming 2% failure over five years, we estimated that the number to treat to
      avoid one revision was 107 for oral bisphosphonates. Conclusions In patients
      undergoing lower limb arthroplasty, bisphosphonate use was associated with an
      almost twofold increase in implant survival time. These findings require
      replication and testing in experimental studies for confirmation.

PMID- 22147912
TI  - IgA and IgG antineutrophil cytoplasmic antibody engagement of Fc receptor genetic
      variants influences granulomatosis with polyangiitis.
AB  - Granulomatosis with polyangiitis (Wegener's) is a rare autoimmune neutrophil
      mediated vasculitis that can cause renal disease and mucosal manifestations.
      Antineutrophil cytoplasmic antibodies (ANCA) are present in many patients, vary
      in level over time, and induce neutrophil activation through engagement with Fc
      receptors (FcRs). Given roles for FcRs in ANCA-mediated neutrophil activation and
      IgA antibodies in mucosal immunity, we hypothesized that FcR genetics and
      previously unappreciated IgA ANCA affect clinical presentation. We assembled a
      total of 673 patients and 413 controls from two multicenter cohorts, performed
      ELISA and immunofluorescence assays to determine IgA and IgG ANCA positivity, and
      used Illumina, TaqMan, or Pyrosequencing to genotype eight haplotype-tagging SNPs
      in the IgA FcR (FCAR) and to determine NA1/NA2 genotype of FCGR3B, the most
      prevalent neutrophil IgG FcR. We evaluated neutrophil activation by measuring
      degranulation marker CD11b with flow cytometry or neutrophil extracellcular trap
      formation with confocal microscopy. Functional polymorphisms in FCGR3B and FCAR
      differed between patient groups stratified by renal involvement. IgA ANCA were
      found in ~30% of patients and were less common in patients with severe renal
      disease. Neutrophil stimulation by IgA or IgG ANCA led to degranulation and
      neutrophil extracellcular trap formation in a FcR allele-specific manner
      (IgA:FCAR P = 0.008; IgG:FCGR3B P = 0.003). When stimulated with IgA and IgG ANCA
      together, IgG ANCA induced neutrophil activation was reduced (P = 0.0001). FcR
      genotypes, IgA ANCA, and IgG ANCA are potential prognostic and therapeutic
      targets for understanding the pathogenesis and presentation of granulomatosis
      with polyangiitis (Wegener's).

PMID- 22147913
TI  - Evidence for a hierarchy of predictions and prediction errors in human cortex.
AB  - According to hierarchical predictive coding models, the cortex constantly
      generates predictions of incoming stimuli at multiple levels of processing.
      Responses to auditory mismatches and omissions are interpreted as reflecting the
      prediction error when these predictions are violated. An alternative
      interpretation, however, is that neurons passively adapt to repeated stimuli. We
      separated these alternative interpretations by designing a hierarchical auditory
      novelty paradigm and recording human EEG and magnetoencephalographic (MEG)
      responses to mismatching or omitted stimuli. In the crucial condition,
      participants listened to frequent series of four identical tones followed by a
      fifth different tone, which generates a mismatch response. Because this response
      itself is frequent and expected, the hierarchical predictive coding hypothesis
      suggests that it should be cancelled out by a higher-order prediction. Three
      consequences ensue. First, the mismatch response should be larger when it is
      unexpected than when it is expected. Second, a perfectly monotonic sequence of
      five identical tones should now elicit a higher-order novelty response. Third,
      omitting the fifth tone should reveal the brain's hierarchical predictions. The
      rationale here is that, when a deviant tone is expected, its omission represents
      a violation of two expectations: a local prediction of a tone plus a
      hierarchically higher expectation of its deviancy. Thus, such an omission should
      induce a greater prediction error than when a standard tone is expected.
      Simultaneous EEE- magnetoencephalographic recordings verify those predictions and
      thus strongly support the predictive coding hypothesis. Higher-order predictions
      appear to be generated in multiple areas of frontal and associative cortices.

PMID- 22147914
TI  - Cullin 3 mediates SRC-3 ubiquitination and degradation to control the retinoic
      acid response.
AB  - SRC-3 is an important coactivator of nuclear receptors including the retinoic
      acid (RA) receptor alpha. Most of SRC-3 functions are facilitated by changes in
      the posttranslational code of the protein that involves mainly phosphorylation
      and ubiquitination. We recently reported that SRC-3 is degraded by the proteasome
      in response to RA. Here, by using an RNAi E3-ubiquitin ligase entry screen, we
      identified CUL-3 and RBX1 as components of the E3 ubiquitin ligase involved in
      the RA-induced ubiquitination and subsequent degradation of SRC-3. We also show
      that the RA-induced ubiquitination of SRC-3 depends on its prior phosphorylation
      at serine 860 that promotes binding of the CUL-3-based E3 ligase in the nucleus.
      Finally, phosphorylation, ubiquitination, and degradation of SRC-3 cooperate to
      control the dynamics of transcription. In all, this process participates to the
      antiproliferative effect of RA.

PMID- 22147915
TI  - Pannexins in ischemia-induced neurodegeneration.
AB  - Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) form large-pore nonselective
      channels in the plasma membrane of cells and were suggested to play a role in the
      pathophysiology of cerebral ischemia. To directly test a potential contribution
      of pannexins in ischemia-related mechanisms, we performed experiments in Px1(-/
      ), Px2(-/-), and Px1(-/-)Px2(-/-) knockout mice. IL-1beta release, channel
      function in astrocytes, and cortical spreading depolarization were not altered in
      Px1(-/-)Px2(-/-) mice, indicating that, in contrast to previous concepts, these
      processes occur normally in the absence of pannexin channels. However, ischemia
      induced dye release from cortical neurons was lower, indicating that channel
      function in Px1(-/-)Px2(-/-) neurons was impaired. Furthermore, Px1(-/-)Px2(-/-)
      mice had a better functional outcome and smaller infarcts than wild-type mice
      when subjected to ischemic stroke. In conclusion, our data demonstrate that Px1
      and Px2 underlie channel function in neurons and contribute to ischemic brain
      damage.

PMID- 22147916
TI  - Estimation of 3D shape from image orientations.
AB  - One of the main functions of vision is to estimate the 3D shape of objects in our
      environment. Many different visual cues, such as stereopsis, motion parallax, and
      shading, are thought to be involved. One important cue that remains poorly
      understood comes from surface texture markings. When a textured surface is
      slanted in 3D relative to the observer, the surface patterns appear compressed in
      the retinal image, providing potentially important information about 3D shape.
      What is not known, however, is how the brain actually measures this information
      from the retinal image. Here, we explain how the key information could be
      extracted by populations of cells tuned to different orientations and spatial
      frequencies, like those found in the primary visual cortex. To test this theory,
      we created stimuli that selectively stimulate such cell populations, by
      "smearing" (filtering) images of 2D random noise into specific oriented patterns.
      We find that the resulting patterns appear vividly 3D, and that increasing the
      strength of the orientation signals progressively increases the sense of 3D
      shape, even though the filtering we apply is physically inconsistent with what
      would occur with a real object. This finding suggests we have isolated key
      mechanisms used by the brain to estimate shape from texture. Crucially, we also
      find that adapting the visual system's orientation detectors to orthogonal
      patterns causes unoriented random noise to look like a specific 3D shape.
      Together these findings demonstrate a crucial role of orientation detectors in
      the perception of 3D shape.

PMID- 22147918
TI  - Aberrant expression of metastasis-inducing proteins in ectopic and matched
      eutopic endometrium of women with endometriosis: implications for the
      pathogenesis of endometriosis.
AB  - BACKGROUND: Endometriosis is a metastatic disease without obvious tumorigenesis.
      Expression of S100P, S100A4, osteopontin (OPN) or anterior gradient homologue 2
      (AGR2) proteins can induce metastasis but fail to induce tumorigenesis per se. We
      now explore whether this group of metastasis-inducing proteins (MIPs) are
      associated with the pathogenesis of endometriosis. METHODS: Eutopic endometrial
      biopsies were taken from 73 women (35 fertile women without endometriosis and 38
      women with surgically diagnosed endometriosis). Ectopic endometriotic lesions
      were collected from eight of the women with endometriosis. The expression of MIPs
      at the cellular level was evaluated by immunohistochemistry and the presence of
      these proteins in the endometrial tissues was verified by western blotting and
      their gene expression was confirmed by RT-PCR. RESULTS: All four MIPs were
      immunolocated in the endometrium of control women and S100P, AGR2 and OPN showed
      a cyclical variation. Proliferative phase eutopic endometrium of both groups
      showed a similar staining pattern for all MIPs, whereas secretory phase
      endometrium showed a differential expression between controls and cases. The
      secretory phase endometrial immunostaining of controls showed weak stromal and
      perivascular AGR2, and decreased stromal and glandular S100P. In contrast,
      immunostaining for all MIPs was increased in the late secretory endometrial
      samples of women with endometriosis and intense immunostaining was seen for
      S100A4 in the stroma (P< 0.05) and for S100P (P< 0.001) and AGR2 (P< 0.0001) in
      both glands and stroma (P< 0.001). All active peritoneal endometriotic lesions
      showed strong immunostaining for each of the MIPs studied. CONCLUSIONS: We
      propose that these MIPs enhance endometrial cell invasiveness and contribute to
      the establishment of ectopic endometriotic deposits after retrograde
      menstruation.

PMID- 22147919
TI  - Symmetrical division of mouse oocytes during meiotic maturation can lead to the
      development of twin embryos that amalgamate to form a chimeric hermaphrodite.
AB  - BACKGROUND: Gentle compression of mouse oocytes during meiosis-1 prevented the
      usual extrusion of a small polar body and resulted in the symmetrical division of
      the ooplasm into two cells of similar size within the zona pellucida. The purpose
      of our study was to determine whether such cells, equivalent to two small
      oocytes, were capable of embryonic development and would result in birth
      following transfer to the uterus. METHODS: IVF of the 2-celled oocytes was
      performed and the twin intra-zonal embryos were observed. In each case, the two
      embryos that originated from fertilized cells with two pronuclei were observed to
      amalgamate and form a single morula and subsequent blastocyst that was
      transferred to the uterus of a recipient of a different mouse strain. FISH
      analysis was performed on sectioned paraffin-embedded tissue of the offspring.
      RESULTS: In symmetrically divided oocytes each cell contained a metaphase II
      spindle. Both cells were fertilizable and cleaved to form twin embryos within the
      same zona pellucida. Most twin embryos amalgamated to form a single compacted
      morula, which progressed to hatched blastocysts that contained a single inner
      cell mass. In total, 104 of these blastocysts were transferred to 19 mice, two of
      which became pregnant, resulting in the birth of three offspring. FISH analysis
      showed that one newborn contained both XX and XY cells. CONCLUSIONS: We found
      that two small oocytes fertilized within the same zona pellucida to form twin
      embryos that amalgamate to establish a single chimeric embryo. This may be one
      mechanism that leads to the formation of a chimeric hermaphrodite when an embryo
      containing XX cells mixes with its intra-zonal twin containing XY cells.

PMID- 22147920
TI  - Consensus on women's health aspects of polycystic ovary syndrome (PCOS).
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females
      with a high prevalence. The etiology of this heterogeneous condition remains
      obscure and its phenotype expression varies. Two, widely cited, previous
      ESHRE/ASRM-sponsored PCOS consensus workshops focused on diagnosis (published in
      2004) and infertility management (published in 2008). The present third PCOS
      consensus paper summarizes current knowledge and identifies knowledge gaps
      regarding various women's health aspects of PCOS. Relevant topics addressed-all
      dealt with in a systematic fashion-include adolescence, hirsutism and acne,
      contraception, menstrual cycle abnormalities, quality of life, ethnicity,
      pregnancy complications, long-term metabolic and cardiovascular health and
      finally cancer risk. Additional, comprehensive background information is provided
      separately in an extended online publication.

PMID- 22147921
TI  - Prosthetic valve, fever and arthropathy--still a difficult diagnosis.

PMID- 22147922
TI  - Diazoxide for the treatment of hypoglycaemic dumping syndrome.

PMID- 22147923
TI  - Dose area product measurement for diagnostic reference levels and analysis of
      patient dose in dental radiography.
AB  - In this study, diagnostic reference levels (DRLs) were suggested and patient
      doses were analysed through the dose-area product value in dental radiography. In
      intraoral radiography, at three sites, i.e. molar, premolar and incisor on the
      maxilla and acquired third quartile values: 55.5, 46 and 36.5 mGy cm(2),
      respectively, were measured. In panoramic, cephalometric and cone beam computed
      tomography, the values were 120.3, 146 and 3203 mGy cm(2) (16 * 18 cm),
      respectively. It has been shown that, in intraoral radiography, the patient dose
      changes proportionally to the value of mA s, but the change in extraoral
      radiography in response to mA s could not be confirmed. The authors could
      confirm, however, the difference in dose according to the manufacturer in all
      dental radiography examinations, except for panoramic radiography. Depending on
      the size of hospital, there were some differences in patient dose in intraoral
      radiography, but no difference in patient dose in extraoral radiography.

PMID- 22147924
TI  - Hand exposure of nuclear medicine workers during administration of radioiodine.
AB  - (131)I has been widely used in nuclear medicine for many years, particularly in
      the form of iodide for the diagnosis and therapy of thyroid cancer and other
      thyroid diseases. Manual dispensing of radioiodine-based radiopharmaceuticals
      results in potentially significant radiation doses to the hands of nuclear
      medicine personnel performing this task. This article reports the results of
      thermoluminescent dosemeter-based measurement of radiation doses at various
      points on the hands of personnel dispensing radioiodine radiopharmaceuticals.

PMID- 22147925
TI  - Diagnostic reference level of computed tomography (CT) in Japan.
AB  - Optimisation of computed tomography (CT) parameters is important in avoiding
      excess radiation exposure. The aim of this study is to establish the diagnostic
      reference levels (DRL) of CT in Japan by using dose-length product (DLP).
      Datasheets were sent to all hospitals/clinics which had CT scanner(s) in Gunma
      prefecture. Data were obtained for all patients who underwent CT during a single
      month (June 2010), and the distributions of DLP were evaluated for eight
      anatomical regions and five patient age groups. The DRL was defined as the 25th
      and 75th percentiles of DLP. Datasheets were collected from 80 of 192
      hospitals/clinics (26 090 patients). DLP for head CT of paediatric patients
      tended to be higher in Japan compared with DRLs of paediatric head CTs reported
      from the EU or Syria. Although this study was performed with limited samples, DLP
      for adult patients were at comparable levels for all anatomical regions.

PMID- 22147926
TI  - Natural radionuclide concentrations in granite rocks in Aswan and Central
      Southern Eastern Desert, Egypt and their radiological implications.
AB  - Different types of granites, used extensively in local construction, were
      collected from five localities in Egypt, namely: Abu Ziran (Central Eastern
      Desert), Gabal El Maesala (Aswan) and three areas from Wadi Allaqi, (Gabal Abu
      Marw, Gabal Haumor and Gabal um Shalman), in the South Eastern Desert. Granite
      samples were studied radiologically, petrographically and geochemically. The
      contents of natural radionuclides ((226)Ra, (232)Th and (40)K) were measured in
      investigated samples by using gamma spectrometry [NaI (Tl) 3'*3']. The activity
      concentrations of (226)Ra, (232)Th and (40)K in the selected granite samples
      ranged from 9+/-0.5 to 111+/-7, 8+/-1 to 75+/-4 and 100+/-6 to 790+/-40 Bq kg(
      1), respectively. The external hazard index (H(ex)), absorbed dose and annual
      effective dose rate were evaluated to assess the radiation hazard for people
      living in dwellings made of the materials studied. The calculated radium
      equivalents were lower than the values recommended for construction materials
      (370 Bq kg(-1)). The excess lifetime cancer risks were also calculated.
      Petrographically, the granites studied are varied in the form of potash-feldspar,
      quartz, plagioclase, mica and hornblende. The accessory minerals are zircon,
      apatite and allanite. Geochemically, the chemical composition of the granite is
      studied especially for major oxides. They are characterized to have SiO(2),
      K(2)O, Na(2)O and Al(2)O(3) with depletion in CaO, MgO, TiO(2) and P(2)O(5).

PMID- 22147927
TI  - The monetary value of the man-mSv for Korean NPP radiation workers assessed by
      the radiation aversion factor.
AB  - The monetary value of the man-mSv for operators of Korean nuclear power plants
      (NPPs) was calculated using a radiation aversion factor based on a survey of NPP
      workers. Initially, the life expectancy in the population is 79.4 y, the average
      age of cancer occurrence is 60 y, the average annual wage for an electric worker
      is 56 000 $ y(-1) and the nominal risk coefficient induced by radiation is 4.2E(
      5) mSv were used to evaluate the basic monetary value (alpha(base)) resulting in
      45.6 $ mSv(-1). To investigate the degree of radiation aversion, the subject of
      the investigation was selected as the working radiation workers in 10 NPPs in
      Korea (Kori 1-2, Yeonggwang 1-3, Ulchin 1-3 and Wolseong 1-2). In August 2010,
      with the cooperation of KHNP and partner companies, a total of 2500 survey
      questionnaires to 10 NPPs (or 250 surveys to each NPP) were distributed to
      currently employed radiation workers. From these, 2157 responses were obtained
      between August and October 2010. The assessed radiation aversion factor and the
      monetary value of the man-mSv from the calculated radiation aversion factor were
      1.26 and ~50 $ in the 0-1 mSv range, 1.38 and ~200 $ in the 1-5 mSv range, 1.52
      and ~1000 $ in the 5-10 mSv range, 1.65 and ~4000 $ in the 10-20 mSv range and
      1.74 and ~8500 $ >20 mSv.

PMID- 22147928
TI  - Anatomy of the dural venous sinuses.

PMID- 22147929
TI  - Experts foresee no quick resolution to intertwined issues of US deficit reduction
      and healthcare reform.

PMID- 22147930
TI  - German internet clinic based in London angers German doctors.

PMID- 22147931
TI  - Licensed home tests will be introduced to reduce undiagnosed HIV.

PMID- 22147932
TI  - Gynaecologist is struck off for botching vaginal surgery and dishonesty.

PMID- 22147933
TI  - New body aims to streamline approval and regulation of research in NHS.

PMID- 22147934
TI  - Data collection helps to close gap in treatment of lung cancer patients.

PMID- 22147935
TI  - A third of all cancers in the UK are potentially preventable, finds review.

PMID- 22147937
TI  - Prognostic immune markers in non-small cell lung cancer--letter.

PMID- 22147939
TI  - IL-6 and ovarian cancer--letter.

PMID- 22147940
TI  - Opposing effects of Runx2 and estradiol on breast cancer cell proliferation: in
      vitro identification of reciprocally regulated gene signature related to clinical
      letrozole responsiveness.
AB  - PURPOSE: To assess the clinical significance of the interaction between estrogen
      and Runx2 signaling, previously shown in vitro. EXPERIMENTAL DESIGN:
      MCF7/Rx2(dox) breast cancer cells were treated with estradiol and/or doxycycline
      to induce Runx2, and global gene expression was profiled to define genes
      regulated by estradiol, Runx2, or both. Anchorage-independent growth was assessed
      by soft-agar colony formation assays. Expression of gene sets defined using the
      MCF7/Rx2(dox) system was analyzed in pre- and on-treatment biopsies from hormone
      receptor-positive patients undergoing neoadjuvant letrozole treatment in two
      independent studies, and short-term changes in gene expression were correlated
      with tumor size reduction or Ki67 index at surgery. RESULTS: Reflecting its
      oncogenic property, estradiol strongly promoted soft-agar colony formation,
      whereas Runx2 blocked this process suggesting tumor suppressor property.
      Transcriptome analysis of MCF7/Rx2(dox) cells treated with estradiol and/or
      doxycycline showed reciprocal attenuation of Runx2 and estrogen signaling.
      Correspondingly in breast cancer tumors, expression of estradiol- and Runx2
      regulated genes was inversely correlated, and letrozole increased expression of
      Runx2-stimulated genes, as defined in the MCF7/Rx2(dox) model. Of particular
      interest was a gene set upregulated by estradiol and downregulated by Runx2 in
      vitro; its short-term response to letrozole treatment associated with tumor size
      reduction and Ki67 index at surgery better than other estradiol-regulated gene
      sets. CONCLUSION: This work provides clinical evidence for the importance of
      antagonism between Runx2 and E2 signaling in breast cancer. Likely sensing the
      tension between them, letrozole responsiveness of a genomic node, positively
      regulated by estradiol and negatively regulated by Runx2 in vitro, best
      correlated with the clinical efficacy of letrozole treatment.

PMID- 22147941
TI  - A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria
      vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of
      safety and immune induction.
AB  - PURPOSE: Listeria monocytogenes (Lm)-based vaccines stimulate both innate and
      adaptive immunity. ANZ-100 is a live-attenuated Lm strain (Lm
      DeltaactA/DeltainlB). Uptake by phagocytes in the liver results in local
      inflammatory responses and activation and recruitment of natural killer (NK) and
      T cells, in association with increased survival of mice bearing hepatic
      metastases. The Lm DeltaactA/DeltainlB strain, engineered to express human
      mesothelin (CRS-207), a tumor-associated antigen expressed by a variety of
      tumors, induces mesothelin-specific T-cell responses against mesothelin
      expressing murine tumors. These two phase I studies test ANZ-100 and CRS-207 in
      subjects with liver metastases and mesothelin-expressing cancers, respectively.
      EXPERIMENTAL DESIGN: A single intravenous injection of ANZ-100 was evaluated in a
      dose escalation study in subjects with liver metastases. Nine subjects received 1
      * 10(6), 3 * 10(7), or 3 * 10(8) colony-forming units (cfu). CRS-207 was
      evaluated in a dose-escalation study in subjects with mesothelioma, lung,
      pancreatic, or ovarian cancers. Seventeen subjects received up to 4 doses of 1 *
      10(8), 3 * 10(8), 1 * 10(9), or 1 * 10(10) cfu. RESULTS: A single infusion of ANZ
      100 was well tolerated to the maximum planned dose. Adverse events included
      transient laboratory abnormalities and symptoms associated with cytokine release.
      Multiple infusions of CRS-207 were well tolerated up to 1 * 10(9) cfu, the
      determined maximum tolerated dose. Immune activation was observed for both ANZ
      100 and CRS-207 as measured by serum cytokine/chemokine levels and NK cell
      activation. In the CRS-207 study, listeriolysin O and mesothelin-specific T-cell
      responses were detected and 37% of subjects lived >=15 months. CONCLUSIONS: ANZ
      100 and CRS-207 administration was safe and resulted in immune activation.

PMID- 22147944
TI  - Prevention spending.

PMID- 22147942
TI  - Predictive and prognostic roles of BRAF mutation in stage III colon cancer:
      results from intergroup trial CALGB 89803.
AB  - PURPOSE: Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major
      drivers in colorectal carcinogenesis. In colorectal cancer, BRAF mutation is
      associated with microsatellite instability (MSI), and typically predicts inferior
      prognosis. We examined the effect of BRAF mutation on survival and treatment
      efficacy in patients with stage III colon cancer. METHODS: We assessed status of
      BRAF c.1799T>A (p.V600E) mutation and MSI in 506 stage III colon cancer patients
      enrolled in a randomized adjuvant chemotherapy trial [5-fluorouracil and
      leucovorin (FU/LV) vs. irinotecan (CPT11), FU and LV (IFL); CALGB 89803]. Cox
      proportional hazards model was used to assess the prognostic role of BRAF
      mutation, adjusting for clinical features, adjuvant chemotherapy arm, and MSI
      status. RESULTS: Compared with 431 BRAF wild-type patients, 75 BRAF-mutated
      patients experienced significantly worse overall survival [OS; log-rank P =
      0.015; multivariate HR = 1.66; 95% CI: 1.05-2.63]. By assessing combined status
      of BRAF and MSI, it seemed that BRAF-mutated MSS (microsatellite stable) tumor
      was an unfavorable subtype, whereas BRAF wild-type MSI-high tumor was a favorable
      subtype, and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were
      intermediate subtypes. Among patients with BRAF-mutated tumors, a nonsignificant
      trend toward improved OS was observed for IFL versus FU/LV arm (multivariate HR =
      0.52; 95% CI: 0.25-1.10). Among patients with BRAF wild-type cancer, IFL
      conferred no suggestion of benefit beyond FU/LV alone (multivariate HR = 1.02;
      95% CI: 0.72-1.46). CONCLUSIONS: BRAF mutation is associated with inferior
      survival in stage III colon cancer. Additional studies are necessary to assess
      whether there is any predictive role of BRAF mutation for irinotecan-based
      therapy.

PMID- 22147945
TI  - The leap of faith from disease treatment to lifestyle prevention: the genealogy
      of a policy idea.
AB  - Since the 1970s public health policy has attempted to counter the rise of chronic
      diseases by getting individuals to make healthy choices about smoking, alcohol,
      diet, and physical exercise. Inspired by the so-called new perspective of the
      1974 Lalonde report, this shift from disease treatment to prevention has been a
      key focus of public health policy to this day. Every generation of public health
      reports presents prevention as the answer to past failures, but the continuous
      experience of failure is strangely coexistent with a fundamental belief in the
      ability of lifestyle prevention to produce large health improvements. The article
      tracks the genealogy of lifestyle prevention as policy idea across three
      generations of U.S. and Danish public health reports and finds a systematic
      interpretation of lifestyle prevention as being more successful and promising
      than acute medical treatment.

PMID- 22147946
TI  - The role of law in public health preparedness: opportunities and challenges.
AB  - We report the results of a study designed to assess and evaluate how the law
      shapes the public health system's preparedness activities. Based on 144
      qualitative interviews conducted in nine states, we used a model that compared
      the objective legal environment with how practitioners perceived the laws. Most
      local public health and emergency management professionals relied on what they
      perceived the legal environment to be rather than on an adequate understanding of
      the objective legal requirements. Major reasons for the gap include the lack of
      legal training for local practitioners and the difficulty of obtaining
      clarification and consistent legal advice regarding public health preparedness.
      Narrowing the gap would most likely improve preparedness outcomes. We conclude
      that there are serious deficiencies in legal preparedness that can undermine
      effective responses to public health emergencies. Correcting the lack of legal
      knowledge, coupled with eliminating delays in resolving legal issues and
      questions during public health emergencies, could have measurable consequences on
      reducing morbidity and mortality.

PMID- 22147943
TI  - Presynaptic LTP and LTD of excitatory and inhibitory synapses.
AB  - Ubiquitous forms of long-term potentiation (LTP) and depression (LTD) are caused
      by enduring increases or decreases in neurotransmitter release. Such forms or
      presynaptic plasticity are equally observed at excitatory and inhibitory synapses
      and the list of locations expressing presynaptic LTP and LTD continues to grow.
      In addition to the mechanistically distinct forms of postsynaptic plasticity,
      presynaptic plasticity offers a powerful means to modify neural circuits. A wide
      range of induction mechanisms has been identified, some of which occur entirely
      in the presynaptic terminal, whereas others require retrograde signaling from the
      postsynaptic to presynaptic terminals. In spite of this diversity of induction
      mechanisms, some common induction rules can be identified across synapses.
      Although the precise molecular mechanism underlying long-term changes in
      transmitter release in most cases remains unclear, increasing evidence indicates
      that presynaptic LTP and LTD can occur in vivo and likely mediate some forms of
      learning.

PMID- 22147947
TI  - A consideration of user financial incentives to address health inequalities.
AB  - Health inequalities and user financial incentives to encourage health-related
      behavior change are two topical issues in the health policy discourse, and this
      article attempts to combine the two; namely, we try to address whether the latter
      can be used to reduce the former in the contexts of the United Kingdom and the
      United States. Payments for some aspects of medical adherence may offer a
      promising way to address, to some extent, inequalities in health and health care
      in both countries. However, payments for more sustained behavior change, such as
      that associated with smoking cessation and weight loss, have thus far shown
      little long-term effect, although more research that tests the effectiveness of
      different incentive mechanism designs, informed by the findings of behavioral
      economics, ought to be undertaken. Many practical, political, ethical, and
      ideological objections can be waged against user financial incentives in health,
      and this article reviews a number of them, but the justifiability of and limits
      to these incentives require more academic and public discourse so as to gain a
      better understanding of the circumstances in which they can legitimately be used.

PMID- 22147948
TI  - Chronic disease and the shifting focus of public health: is prevention still a
      political lightweight?
AB  - Why is it so politically difficult to obtain government investment in public
      health initiatives that are aimed at addressing chronic disease? This article
      examines the structural disadvantage faced by those who advocate for public
      health policies and practices to reduce chronic disease related to people's
      unhealthy lifestyles and physical environments. It identifies common features
      that make it difficult to establish and maintain initiatives to prevent or reduce
      costly illness and physical suffering: (1) public health benefits are generally
      dispersed and delayed; (2) benefactors of public health are generally unknown and
      taken for granted; (3) the costs of many public health initiatives are
      concentrated and generate opposition from those who would pay them; and (4)
      public health often clashes with moral values or social norms. The article
      concludes by discussing the importance of a new paradigm, "health in all
      policies," that targets the enormous health and economic burdens associated with
      chronic conditions and asserts a need for new policies, practices, and
      participation beyond the confines of traditional public health agencies and
      services.

PMID- 22147950
TI  - Cell fate decisions and axis determination in the early mouse embryo.
AB  - The mouse embryo generates multiple cell lineages, as well as its future body
      axes in the early phase of its development. The early cell fate decisions lead to
      the generation of three lineages in the pre-implantation embryo: the epiblast,
      the primitive endoderm and the trophectoderm. Shortly after implantation, the
      anterior-posterior axis is firmly established. Recent studies have provided a
      better understanding of how the earliest cell fate decisions are regulated in the
      pre-implantation embryo, and how and when the body axes are established in the
      pregastrulation embryo. In this review, we address the timing of the first cell
      fate decisions and of the establishment of embryonic polarity, and we ask how far
      back one can trace their origins.

PMID- 22147951
TI  - Epigenetic reprogramming in mouse pre-implantation development and primordial
      germ cells.
AB  - Epigenetic modifications are crucial for the identity and stability of cells,
      and, when aberrant, can lead to disease. During mouse development, the genome
      wide epigenetic states of pre-implantation embryos and primordial germ cells
      (PGCs) undergo extensive reprogramming. An improved understanding of the
      epigenetic reprogramming mechanisms that occur in these cells should provide
      important new information about the regulation of the epigenetic state of a cell
      and the mechanisms of induced pluripotency. Here, we discuss recent findings
      about the potential mechanisms of epigenetic reprogramming, particularly genome
      wide DNA demethylation, in pre-implantation mouse embryos and PGCs.

PMID- 22147952
TI  - A model of stem cell population dynamics: in silico analysis and in vivo
      validation.
AB  - The proper renewal and maintenance of tissues by stem cell populations is
      simultaneously influenced by anatomical constraints, cell proliferation dynamics
      and cell fate specification. However, their relative influence is difficult to
      examine in vivo. To address this difficulty we built, as a test case, a cell
      centered state-based computational model of key behaviors that govern germline
      development in C. elegans, and used it to drive simulations of cell population
      dynamics under a variety of perturbations. Our analysis provided unexpected
      possible explanations for laboratory observations, including certain 'all-or
      none' phenotypes and complex differentiation patterns. The simulations also
      offered insights into niche-association dynamics and the interplay between cell
      cycle and cell fate. Subsequent experiments validated several predictions
      generated by the simulations. Notably, we found that early cell cycle defects
      influence later maintenance of the progenitor cell population. This general
      modeling approach is potentially applicable to other stem cell systems.

PMID- 22147953
TI  - The muscle pattern of the Drosophila abdomen depends on a subdivision of the
      anterior compartment of each segment.
AB  - In the past, segments were defined by landmarks such as muscle attachments,
      notably by Snodgrass, the king of insect anatomists. Here, we show how an
      objective definition of a segment, based on developmental compartments, can help
      explain the dorsal abdomen of adult Drosophila. The anterior (A) compartment of
      each segment is subdivided into two domains of cells, each responding differently
      to Hedgehog. The anterior of these domains is non-neurogenic and clones lacking
      Notch develop normally; this domain can express stripe and form muscle
      attachments. The posterior domain is neurogenic and clones lacking Notch do not
      form cuticle; this domain is unable to express stripe or form muscle attachments.
      The posterior (P) compartment does not form muscle attachments. Our in vivo films
      indicate that early in the pupa the anterior domain of the A compartment
      expresses stripe in a narrowing zone that attracts the extending myotubes and
      resolves into the attachment sites for the dorsal abdominal muscles. We map the
      tendon cells precisely and show that all are confined to the anterior domain of
      A. It follows that the dorsal abdominal muscles are intersegmental, spanning from
      one anterior domain to the next. This view is tested and supported by clones that
      change cell identity or express stripe ectopically. It seems that growing
      myotubes originate in posterior A and extend forwards and backwards until they
      encounter and attach to anterior A cells. The dorsal adult muscles are polarised
      in the anteroposterior axis: we disprove the hypothesis that muscle orientation
      depends on genes that define planar cell polarity in the epidermis.

PMID- 22147954
TI  - Wnt/PCP proteins regulate stereotyped axon branch extension in Drosophila.
AB  - Branching morphology is a hallmark feature of axons and dendrites and is
      essential for neuronal connectivity. To understand how this develops, I analyzed
      the stereotyped pattern of Drosophila mushroom body (MB) neurons, which have
      single axons branches that extend dorsally and medially. I found that components
      of the Wnt/Planar Cell Polarity (PCP) pathway control MB axon branching. frizzled
      mutant animals showed a predominant loss of dorsal branch extension, whereas
      strabismus (also known as Van Gogh) mutants preferentially lost medial branches.
      Further results suggest that Frizzled and Strabismus act independently.
      Nonetheless, branching fates are determined by complex Wnt/PCP interactions,
      including interactions with Dishevelled and Prickle that function in a context
      dependent manner. Branching decisions are MB-autonomous but non-cell-autonomous
      as mutant and non-mutant neurons regulate these decisions collectively. I found
      that Wnt/PCP components do not need to be asymmetrically localized to distinct
      branches to execute branching functions. However, Prickle axonal localization
      depends on Frizzled and Strabismus.

PMID- 22147955
TI  - Engrailed homeoprotein recruits the adenosine A1 receptor to potentiate ephrin A5
      function in retinal growth cones.
AB  - Engrailed 1 and engrailed 2 homeoprotein transcription factors (collectively
      Engrailed) display graded expression in the chick optic tectum where they
      participate in retino-tectal patterning. In vitro, extracellular Engrailed guides
      retinal ganglion cell (RGC) axons and synergises with ephrin A5 to provoke the
      collapse of temporal growth cones. In vivo disruption of endogenous extracellular
      Engrailed leads to misrouting of RGC axons. Here we characterise the signalling
      pathway of extracellular Engrailed. Our results show that Engrailed/ephrin A5
      synergy in growth cone collapse involves adenosine A1 receptor activation after
      Engrailed-dependent ATP synthesis, followed by ATP secretion and hydrolysis to
      adenosine. This is, to our knowledge, the first evidence for a role of the
      adenosine A1 receptor in axon guidance. Based on these results, together with
      higher expression of the adenosine A1 receptor in temporal than nasal growth
      cones, we propose a computational model that illustrates how the interaction
      between Engrailed, ephrin A5 and adenosine could increase the precision of the
      retinal projection map.

PMID- 22147956
TI  - Genetics of thyroid function and disease.
AB  - Genetics play a prominent role in both determination of thyroid hormone and
      thyrotropin (TSH) concentrations, and susceptibility to autoimmune thyroid
      disease. Heritability studies have suggested that up to 67% of circulating
      thyroid hormone and TSH concentrations are genetically determined, suggesting a
      genetic basis for narrow intra-individual variation in levels, perhaps a genetic
      'set point'. The search for the genes responsible has revealed several
      candidates, including the genes for phosphodiesterase 8B, iodothyronine
      deiodinase 1, F-actin-capping protein subunit beta and the TSH receptor; however,
      each of these only contributes a small amount to the variability of hormone
      concentrations, suggesting that further genes and mechanisms of genetic influence
      are yet to be discovered. Some genes known to influence thyroid function,
      including iodothyronine deiodinase 2 and the TSH receptor, have been shown to
      influence a wide range of clinical and developmental phenotypes from bone health
      to neurological development and longevity; such observations will help us
      understand the complex action of thyroid hormones on individual tissues. Finally,
      autoimmune thyroid disease commonly runs in families, and the search for genes
      which increase susceptibility has identified several good candidates,
      particularly those involved in immune regulation and thyroid function. However,
      these genes alone account for only a small percentage of the current prevalence
      of these disorders. Although the advancement of genetic technology has led to
      many significant findings in the last decade or two, it is clear that we are only
      just beginning to understand the role of genetics in thyroid function and
      disease.

PMID- 22147957
TI  - Next-generation sequencing for cancer diagnostics: a practical perspective.
AB  - Next-generation sequencing (NGS) is arguably one of the most significant
      technological advances in the biological sciences of the last 30 years. The
      second generation sequencing platforms have advanced rapidly to the point that
      several genomes can now be sequenced simultaneously in a single instrument run in
      under two weeks. Targeted DNA enrichment methods allow even higher genome
      throughput at a reduced cost per sample. Medical research has embraced the
      technology and the cancer field is at the forefront of these efforts given the
      genetic aspects of the disease. World-wide efforts to catalogue mutations in
      multiple cancer types are underway and this is likely to lead to new discoveries
      that will be translated to new diagnostic, prognostic and therapeutic targets.
      NGS is now maturing to the point where it is being considered by many
      laboratories for routine diagnostic use. The sensitivity, speed and reduced cost
      per sample make it a highly attractive platform compared to other sequencing
      modalities. Moreover, as we identify more genetic determinants of cancer there is
      a greater need to adopt multi-gene assays that can quickly and reliably sequence
      complete genes from individual patient samples. Whilst widespread and routine use
      of whole genome sequencing is likely to be a few years away, there are immediate
      opportunities to implement NGS for clinical use. Here we review the technology,
      methods and applications that can be immediately considered and some of the
      challenges that lie ahead.

PMID- 22147958
TI  - Semantic Processing and Thought Disorder in Childhood-Onset Schizophrenia:
      Insights from fMRI.
AB  - Impairments in language processing and thought disorder are core symptoms of
      schizophrenia. Here we used fMRI to investigate functional abnormalities in the
      neural networks subserving sentence-level language processing in childhood-onset
      schizophrenia (COS). Fourteen children with COS (mean age: 13.34; IQ: 95) and 14
      healthy controls (HC; mean age: 12.37; IQ: 104) underwent fMRI while performing a
      semantic judgment task previously shown to differentially engage semantic and
      syntactic processes. We report four main results. First, different patterns of
      functional specialization for semantic and syntactic processing were observed
      within each group, despite similar level of task performance. Second, after
      regressing out IQ, significant between-group differences were observed in the
      neural correlates of semantic and, to a lesser extent, syntactic processing, with
      HC children showing overall greater activity than COS children. Third, while
      these group differences were not related to effects of medications, a significant
      negative correlation was observed in the COS group between neuroleptic dosage and
      activity in the left inferior frontal gyrus for the semantic condition. Finally,
      COS children's level of thought disorder was significantly correlated with task
      related activity in language-relevant networks. Taken together, these findings
      suggest that children with COS exhibit aberrant patterns of neural activity
      during semantic, and to a lesser extent syntactic, processing and that these
      functional abnormalities in language-relevant networks are significantly related
      to severity of thought disorder.

PMID- 22147959
TI  - Pathophysiology and prevention of postoperative peritoneal adhesions.
AB  - Peritoneal adhesions represent an important clinical challenge in
      gastrointestinal surgery. Peritoneal adhesions are a consequence of peritoneal
      irritation by infection or surgical trauma, and may be considered as the
      pathological part of healing following any peritoneal injury, particularly due to
      abdominal surgery. The balance between fibrin deposition and degradation is
      critical in determining normal peritoneal healing or adhesion formation.
      Postoperative peritoneal adhesions are a major cause of morbidity resulting in
      multiple complications, many of which may manifest several years after the
      initial surgical procedure. In addition to acute small bowel obstruction,
      peritoneal adhesions may cause pelvic or abdominal pain, and infertility. In this
      paper, the authors reviewed the epidemiology, pathogenesis and various prevention
      strategies of adhesion formation, using Medline and PubMed search. Several
      preventive agents against postoperative peritoneal adhesions have been
      investigated. Their role aims in activating fibrinolysis, hampering coagulation,
      diminishing the inflammatory response, inhibiting collagen synthesis or creating
      a barrier between adjacent wound surfaces. Their results are encouraging but most
      of them are contradictory and achieved mostly in animal model. Until additional
      findings from future clinical researches, only a meticulous surgery can be
      recommended to reduce unnecessary morbidity and mortality rates from these
      untoward effects of surgery. In the current state of knowledge, pre-clinical or
      clinical studies are still necessary to evaluate the effectiveness of the several
      proposed prevention strategies of postoperative peritoneal adhesions.

PMID- 22147960
TI  - Endoscopic management of chronic radiation proctitis.
AB  - Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic
      radiotherapy. Although many cases resolve spontaneously, some lead to chronic
      symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding
      with iron deficiency anemia requiring blood transfusions. Treatments for chronic
      radiation proctitis remain unsatisfactory and the basis of evidence for various
      therapies is generally insufficient. There are very few controlled or prospective
      trials, and comparisons between therapies are limited because of different
      evaluation methods. Medical treatments, including formalin, topical sucralfate, 5
      amino salicylic acid enemas, and short chain fatty acids have been used with
      limited success. Surgical management is associated with high morbidity and
      mortality. Endoscopic therapy using modalities such as the heater probe,
      neodymium:yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and
      bipolar electrocoagulation has been reported to be of some benefit, but with
      frequent complications. Argon plasma coagulation is touted to be the preferred
      endoscopic therapy due to its efficacy and safety profile. Newer methods of
      endoscopic ablation such as radiofrequency ablation and cryotherapy have been
      recently described which may afford broader areas of treatment per application,
      with lower rate of complications. This review will focus on endoscopic ablation
      therapies, including such newer modalities, for chronic radiation proctitis.

PMID- 22147961
TI  - Elevated serum alpha fetoprotein levels promote pathological progression of
      hepatocellular carcinoma.
AB  - AIM: To investigate the biological role of alpha fetoprotein (AFP) and its
      clinical significance in carcinogenesis of hepatocellular carcinoma (HCC).
      METHODS: Clinical analysis of HCC patients and immunohistochemical examination
      were conducted to evaluate the relationship between serum AFP level and patient
      mortality. Confocal microscopy, Western blotting, dimethylthiahzolyl-2,5-diphenyl
      tetrazolium bromide, Cell Counting Kit-8 assays and flow cytometry were performed
      to explore the possible mechanism. RESULTS: Among the 160 HCC patients enrolled
      in this study, 130 patients survived 2 years (81.25%), with a survival rate of
      86.8% in AFP < 2 0 MUg/L group, 88.9% in AFP 20-250 MUg/L group, and 69.6% in AFP
      > 250 MUg/L group, demonstrating a higher mortality rate in HCC patients with
      higher AFP levels. Surgical treatment was beneficial only in patients with low
      AFP levels. The mortality rate of HCC patients with high AFP levels who were
      treated surgically was apparently higher than those treated with conservative
      management. The results of immunohistochemistry showed that AFP and AFP receptor
      were merely expressed in tissues of HCC patients with positive serum AFP.
      Consistently, in vitro analysis showed that AFP and AFPS were expressed in HepG2
      but not in HLE cells. AFP showed a capability to promote cell growth, and this
      was more apparent in HepG2 cells, in which the proliferation was increased by 3.5
      folds. Cell cycle analysis showed that the percentage of HepG2 cells in S phase
      after exposure to AFP was modestly increased. CONCLUSION: HCC patients with
      higher AFP levels show a higher mortality rate, which appears to be attributable
      to the growth promoting properties of AFP.

PMID- 22147962
TI  - Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma.
AB  - AIM: To study the relationship between the cyclooxygenase (COX)-2 gene and the
      proliferation and apoptosis of esophageal squamous carcinoma EC109 cells.
      METHODS: The techniques of RNA interference (RNAi) and cell transfection, as well
      as the levels of oncogenicity in nude mice, were used to study the role of COX-2
      in the esophageal squamous carcinoma cell (ESCC) line EC109. Following RNAi and
      transfection, Western blotting analysis was used to determine the expression of
      the COX-2 protein. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium
      bromide (MTT) reduction assay was used to evaluate cell growth, and flow
      cytometry was used to detect cell apoptosis. RESULTS: Western blotting analysis
      demonstrated that COX-2 expression was significantly reduced in EC109 cells
      treated with COX-2-specific short interfering RNA (siRNA) but was increased in
      EC109 cells transfected with COX-2. Furthermore, COX-2 siRNA treatment inhibited
      cell proliferation (P < 0.01) and induced apoptosis in EC109 cells, as determined
      by an MTT assay and by flow cytometry, respectively. In contrast, transfected COX
      2 led to increased cell proliferation (P < 0.05) and decreased apoptosis in EC109
      cells. In addition, combination treatment of cells with COX-2 siRNA and aspirin
      had a synergistic effect (P < 0.01). For experiments measuring tumorigenicity,
      xenograft tumors of a greater volume and weight were found in the COX-2 group
      compared with other groups (P < 0.05). A large dose of aspirin inhibited tumor
      growth in nude mice effectively (P < 0.05), and the rate of tumor suppression was
      51.8% in the high-dose aspirin group. CONCLUSION: COX-2 plays a very critical
      role in ESCC carcinogenesis, and COX-2 siRNA combined with aspirin has the
      potential to be an anticancer therapy for the treatment of ESCC.

PMID- 22147963
TI  - FibroSURE and FibroScan in relation to treatment response in chronic hepatitis C
      virus.
AB  - AIM: To compare histological endpoint assessment using noninvasive alternatives
      to biopsy during treatment in a chronic hepatitis C virus (HCV) cohort. METHODS:
      Patients with chronic HCV were randomized to receive interferon-based therapy for
      24 (genotypes 2/3) or 48 (genotype 1) wk. FibroSURETM (FS) was assessed at
      baseline and at week-12 post-treatment follow-up. Baseline biopsy for METAVIR was
      assessed by a single pathologist. FibroScan((r)) transient elastography (TE) was
      performed during treatment in a patient subset. RESULTS: Two thousand and sixty
      patients (n = 253 in Asia) were classified as METAVIR F0-1 (n = 1682) or F2-4 (n
      = 378). For F2-4, FS (n = 2055) had sensitivity and specificity of 0.87 and 0.61,
      respectively, with area under the receiver-operating curve of 0.82; corresponding
      values for TE (n = 214) and combined FS/TE (n = 209) were 0.77, 0.88 and 0.88,
      and 0.93, 0.68 and 0.88. Overall FS/TE agreement for F2-4 was 71% (kappa = 0.41)
      and higher in Asians vs non-Asians (kappa = 0.86 vs 0.35; P < 0.001). Combined
      FS/TE had 97% accuracy in Asians (n = 33). Baseline FS (0.38 vs 0.51, P < 0.001)
      and TE (8.0 kPa vs 11.9 kPa, P = 0.006) scores were lower in patients with
      sustained virological response than in nonresponders, and were maintained through
      follow-up. CONCLUSION: FS and TE may reliably differentiate mild from moderate
      advanced disease, with a potential for high diagnostic accuracy in Asians with
      chronic HCV.

PMID- 22147964
TI  - Evaluation of Fujinon intelligent chromo endoscopy-assisted capsule endoscopy in
      patients with obscure gastroenterology bleeding.
AB  - AIM: To investigate the potential benefit of Fujinon intelligent chromo endoscopy
      (FICE)-assisted small bowel capsule endoscopy (SBCE) for detection and
      characterization of small bowel lesions in patients with obscure gastroenterology
      bleeding (OGIB). METHODS: The SBCE examinations (Pillcam SB2, Given Imaging Ltd)
      were retrospectively analyzed by two GI fellows (observers) with and without FICE
      enhancement. Randomization was such that a fellow did not assess the same
      examination with and without FICE enhancement. The senior consultant described
      findings as P0, P1 and P2 lesions (non-pathological, intermediate bleed
      potential, high bleed potential), which were considered as reference findings.
      MAIN OUTCOME MEASUREMENTS: Inter-observer correlation was calculated using kappa
      statistics. Sensitivity and specificity for P2 lesions was calculated for FICE
      and white light SBCE. RESULTS: In 60 patients, the intra-class kappa correlations
      between the observers and reference findings were 0.88 and 0.92 (P2), 0.61 and
      0.79 (P1), for SBCE using FICE and white light, respectively. Overall 157 lesions
      were diagnosed using FICE as compared to 114 with white light SBCE (P = 0.15).
      For P2 lesions, the sensitivity was 94% vs 97% and specificity was 95% vs 96% for
      FICE and white light, respectively. Five (P2 lesions) out of 55 arterio-venous
      malformations could be better characterized by FICE as compared to white light
      SBCE. Significantly more P0 lesions were diagnosed when FICE was used as compared
      to white light (39 vs 8, P < 0.001). CONCLUSION: FICE was not better than white
      light for diagnosing and characterizing significant lesions on SBCE for OGIB.
      FICE detected significantly more non-pathological lesions. Nevertheless, some
      vascular lesions could be more accurately characterized with FICE as compared to
      white light SBCE.

PMID- 22147965
TI  - Operative link for gastritis assessment vs operative link on intestinal
      metaplasia assessment.
AB  - AIM: To compare the reliability of gastritis staging systems in ranking gastritis
      associated cancer risk in a large series of consecutive patients. METHODS:
      Gastric mucosal atrophy is the precancerous condition in which intestinal-type
      gastric cancer (GC) most frequently develops. The operative link for gastritis
      assessment (OLGA) staging system ranks the GC risk according to both the
      topography and the severity of gastric atrophy (as assessed histologically on the
      basis of the Sydney protocol for gastric mucosal biopsy). Both cross-sectional
      and long-term follow-up trials have consistently associated OLGA stages III-IV
      with a higher risk of GC. A recently-proposed modification of the OLGA staging
      system (OLGIM) basically incorporates the OLGA frame, but replaces the atrophy
      score with an assessment of intestinal metaplasia (IM) alone. A series of 4552
      consecutive biopsy sets (2007-2009) was retrieved and reassessed according to
      both the OLGA and the OLGIM staging systems. A set of at least 5 biopsy samples
      was available for all the cases considered. RESULTS: In 4460 of 4552 cases
      (98.0%), both the high-risk stages (III + IV) and the low-risk stages (0 +I + II)
      were assessed applying the OLGA and OLGIM criteria. Among the 243 OLGA high-risk
      stages, 14 (5.8%) were down-staged to a low risk using OLGIM. The 67 (1.5%)
      incidentally-found neoplastic lesions (intraepithelial or invasive) were
      consistently associated with high-risk stages, as assessed by both OLGA and OLGIM
      (P < 0.001 for both). Two of 34 intestinal-type GCs coexisting with a high-risk
      OLGA stage (stage III) were associated with a low-risk OLGIM stage (stage II).
      CONCLUSION: Gastritis staging systems (both OLGA and OLGIM) convey prognostically
      important information on the gastritis-associated cancer risk. Because of its
      clinical impact, the stage of gastritis should be included as a conclusive
      message in the gastritis histology report. Since it focuses on IM alone, OLGIM
      staging is less sensitive than OLGA staging in the identification of patients at
      high risk of gastric cancer.

PMID- 22147966
TI  - Comparative study of laparoscopic vs open gastrectomy in gastric cancer
      management.
AB  - AIM: To compare long-term results of gastric cancer patients undergoing
      laparoscopic and open gastrectomy in a single unit. METHODS: From February 2000
      to September 2004, all patients with adenocarcinoma of the stomach were assessed
      to entry in this longitudinal prospective non-randomized trial. Primary endpoint
      was cancer-related survival and secondary endpoints were overall survival,
      evaluation of surgical complications and mortality. RESULTS: Fifty-eight patients
      were enrolled. Forty-seven patients were followed-up (range 11-103, median 38
      mo). Four patients were lost at follow up. Twenty-two patients underwent a
      laparoscopic gastric surgery (LGS) and 25 had a standard open procedure (OGS). No
      statistical difference was found between the two groups in terms of 5 years
      cancer-related mortality rate (50% vs 52%, P = 1), and 5 years overall mortality
      rate (54.5% vs 56%, P = 1). Accordingly, cancer-related and overall survival
      probability by Kaplan-Meier method showed comparable results (P = 0.81 and P =
      0.83, respectively). We found no differences in surgical complications in the 2
      groups. There was no conversion to open surgery in this series. CONCLUSION: LGS
      is as effective as OGS in the management of advanced gastric cancer. However LGS
      cannot be recommended routinely over OGS for the treatment of advanced gastric
      cancer.

PMID- 22147968
TI  - Comparison of presentation and impact on quality of life of gastroesophageal
      reflux disease between young and old adults in a Chinese population.
AB  - AIM: To compare the presentation and impact on quality of life of
      gastroesophageal reflux disease (GERD) in old and young age groups. METHODS: Data
      from adult patients with GERD diagnosed by endoscopic and symptomic
      characteristics were collected between January and November 2009. Exclusion
      criteria included combined peptic ulcers, malignancy, prior surgery, antacid
      medication for more than 2 mo, and pregnancy. Enrolled patients were assigned to
      the elderly group if they were 65 years or older, or the younger group if they
      were under 65 years. They had completed the GERD impact scale, the Chinese GERD
      questionnaire, and the SF-36 questionnaire. Data from other cases without
      endoscopic findings or symptoms were collected and these subjects comprised the
      control group in our study. RESULTS: There were 111 patients with GERD and 44
      normal cases: 78 (70.3%) and 33 patients (29.7%) were in the younger and elderly
      groups, respectively. There were more female patients (60.3%) in the younger
      group, and more males (72.7%) in the elderly group. The younger cases had more
      severe and frequent typical symptoms than the elderly patients. Significantly
      more impairment of daily activities was noted in the younger patients compared
      with the elderly group, except for physical functioning. CONCLUSION: Elderly
      patients with GERD were predominantly male with rare presentation of typical
      symptoms, and had less impaired quality of life compared with younger patients in
      a Chinese population.

PMID- 22147967
TI  - "Liverscore" is predictive of both liver fibrosis and activity in chronic
      hepatitis C.
AB  - AIM: To formulate a noninvasive index predictive of severity of liver fibrosis
      and activity in chronic hepatitis C. METHODS: This cross sectional study was
      conducted on polymerase chain reaction positive, treatment naive patients.
      Fibrosis was staged on a five point scale from F0-F4 and activity was graded on a
      four point scale from A0-A3, according to the METAVIR system. Patients were
      divided into two overall severity groups, minimal disease (< F2 and < A2) and
      significant disease (>= F2 or >= A2). Eleven markers were measured in blood.
      Statistically, the primary outcome variable was identification of minimal and
      significant overall disease. Indices were formulated using beta regression values
      of different combinations of nine statistically significant factors. Diagnostic
      performance of these indices was assessed through receiver-operating
      characteristic curve analysis. RESULTS: A total of 98 patients were included and
      of these 46 had an overall clinically significant disease. Our final six marker
      index, Liverscore for Hepatitis C, consisted of age, alanine transaminase, gamma
      glutamyl transpeptidase, apolipoprotein A-1, alpha-2 macroglobulin and hyaluronic
      acid. The area under the curve was found to be 0.813. On a 0-1 scale, negative
      predictive value at a cutoff level of <= 0.40 was 83%, while positive predictive
      value at >= 0.80 remained 89%. Altogether, 61% of the patients had these
      discriminative scores. CONCLUSION: This index is discriminative of minimal and
      significant overall liver disease in a majority of chronic hepatitis C patients
      and can help in clinical decision making.

PMID- 22147969
TI  - Training gastroenterology fellows to perform gastric polypectomy using a novel ex
      vivo model.
AB  - AIM: To evaluate the effect of hands-on training of gastroenterology fellows in
      gastric polypectomy using an ex vivo simulator. METHODS: Eight gastroenterology
      fellows at Mackay Memorial Hospital, Taipei were evaluated in gastric polypectomy
      techniques using a pig stomach with artificial polyps created by a rubber band
      ligation device. The performance of four second year (year-2) fellows who had
      undergone one year of clinical training was compared with that of four first year
      (year-1) fellows both before and after a 4-h workshop using the ex vivo
      simulator. The workshop allowed for hands-on training in the removal of multiple
      artificial polyps and the placement of hemoclips at the excision site. Evaluation
      included observation of technical skills, procedure time, and the fellows'
      confidence scale. RESULTS: One week after the workshop, the year-1 fellows were
      re-evaluated and had significantly improved mean performance scores (from 17.9 +/
      1.8 to 22.5 +/- 0.7), confidence scale (from 4.5 +/- 1.0 to 7.8 +/- 0.5) and
      procedure time (from 615.0 +/- 57.4 s to 357.5 +/- 85.0 s) compared with their
      baseline performance. After 4 h of training using the ex vivo simulator, the
      skills of the year-1 fellows were statistically similar to those of the year-2
      fellows. CONCLUSION: Use of this ex vivo simulator significantly improved the
      endoscopic gastric polypectomy skills of gastroenterology fellows who had not had
      previous clinical training in gastric polypectomy.

PMID- 22147970
TI  - Primary intestinal non-Hodgkin's lymphoma: a clinicopathologic analysis of 81
      patients.
AB  - AIM: To analyze the clinicopathologic features and the prognosis of primary
      intestinal lymphoma. METHODS: Patients were included in the study based on
      standard diagnostic criteria for primary gastrointestinal lymphoma, and were
      treated at Sun Yat-sen University Cancer Centre between 1993 and 2008. RESULTS:
      The study comprised 81 adults. The most common site was the ileocaecal region.
      Twenty-two point two percent patients had low-grade B-cell lymphoma. Fifty-one
      point nine percent patients had high-grade B-cell lymphoma and 25.9% patients had
      T-cell lymphoma. Most patients had localized disease. There were more patients
      and more early stage diseases in the latter period, and the origin sites changed.
      The majority of patients received the combined treatment, and about 20% patients
      only received nonsurgical therapy. The wverall survival and event-free survival
      rates after 5 years were 71.6% and 60.9% respectively. The multivariate analysis
      revealed that small intestine and ileocaecal region localization, B-cell
      phenotype, and normal lactate dehydrogenase were independent prognostic factors
      for better patient survival. Surgery based treatment did not improve the survival
      rate. CONCLUSION: Refined stratification of the patients according to the
      prognostic variables may allow individualized treatment. Conservative treatment
      may be an optimal therapeutic modality for selected patients.

PMID- 22147971
TI  - S-1 induced secondary acute erythroid leukemia with a chromosome
      inv(12)(p13;q13).
AB  - Adjuvant chemotherapy by S-1 following gastrectomy is considered standard
      treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1
      administration, and that hematological adverse events were relatively rare.
      Pyrimidine anti-metabolites, including S-1, have shown relatively lower risks for
      secondary hematological malignancies in comparison to alkylating agents and
      topoisomerase-II inhibitors. We here report a case of therapy-related leukemia
      after S-1 administration. A patient who had received S-1as the sole adjuvant
      chemotherapy was diagnosed with acute erythroid leukemia. To the best of our
      knowledge, our patient represents the first report of S-1 induced acute leukemia.

PMID- 22147972
TI  - Autoimmune pancreatitis characterized by predominant CD8+ T lymphocyte
      infiltration.
AB  - Autoimmune pancreatitis (AIP) is a rare form of pancreatitis characterized by
      prominent lymphocyte infiltration and pancreatic fibrosis resulting in organ
      dysfunction. The pathogenesis and pathology of AIP remain unknown. A 64-year-old
      Chinese man presented with symptoms and signs of bile duct obstruction diffuse
      enlargement of the head of pancreas, elevated IgG levels, and negative autoimmune
      antibody responses. A pylorus-preserving pancreatoduodenectomy was performed and
      a pancreatic tumor was suspected. However, periductal lymphoplasmacytic
      infiltration and fibrosis were found in the head of pancreas and nearby organs
      instead of tumor cells. Four months after surgery, the patient was readmitted
      because of reoccurrence of severe jaundice and sustained abdominal distension.
      Prednisone 30 mg/d was administered orally as an AIP was suspected. One and a
      half months later, the symptoms of the patient disappeared, and globulin,
      aminotransferase and bilirubin levels decreased significantly. Over a 9-mo follow
      up period, the dose of prednisone was gradually decreased to 10 mg/d and the
      patient remained in good condition. We further demonstrated dominant CD3+/CD8+
      populations, CD20+ cells and a few CD4+ cells in the pancreatic parenchyma,
      duodenum and gallbladder wall by immunohistochemical assay. This AIP case
      presented with significant CD8+ T lymphocyte infiltration in the pancreas and
      extra-pancreatic lesions, indicating that this cell population may be more
      important in mediating AIP pathogenesis than previously known and that AIP might
      be a poorly defined autoimmune disease with heterogeneous pathogenesis.

PMID- 22147973
TI  - Pancreatic cancer risk variant ABO rs505922 in patients with cholangiocarcinoma.
AB  - The aim of this study was to investigate an association between the development
      of cholangiocarcinoma (CCA) and the ABO variant rs505922 (known to increase
      pancreatic cancer risk) in a large cohort of European individuals with CCA. In
      total, 180 individuals with CCA and 350 CCA-free controls were included. The ABO
      variant rs505922 was genotyped using a polymerase chain reaction-based assay.
      Association between this single nucleotide polymorphism (SNP) and CCA was tested
      in contingency tables. Neither allele distributions nor association tests and
      regression analysis provided evidence for an increased risk of CCA among carriers
      of the ABO variant (all P > 0.05). Nevertheless, we documented a deviation from
      Hardy-Weinberg equilibrium in the entire CCA cohort (P = 0.028) and for patients
      with intrahepatic (P = 0.037) but not extrahepatic tumor localization (P > 0.05).
      The association tests did not provide evidence for a prominent role of the
      investigated SNP in the genetic risk of CCA. However, Hardy-Weinberg
      disequilibrium in the entire cohort and the intrahepatic CCA subgroup warrants
      future studies investigating a potential CCA risk modulation by individual blood
      groups.

PMID- 22147974
TI  - Liver transplantation for hepatocellular carcinoma on cirrhosis: strategies to
      avoid tumor recurrence.
AB  - Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide
      and in most cases it is associated with chronic liver disease. Liver
      transplantation (LT) is potentially the optimal treatment for those patients with
      HCC who have a poor functional hepatic reserve due to their underlying chronic
      liver disease. However, due to the limited availability of donors, only those
      patients whose oncologic profile is favorable can be considered for LT. Despite
      the careful selection of candidates based on strict rules, 10 to 20% of liver
      transplant recipients who have HCC in the native cirrhotic liver develop tumor
      recurrence after transplantation. The selection criteria presently employed to
      minimize the risk of recurrence are based on gross tumor characteristics defined
      by imaging techniques; unfortunately, the accuracy of imaging is far from being
      optimal. Furthermore, microscopic tumor features that are strictly linked with
      prognosis can not be assessed prior to transplantation. Pre-transplantation tumor
      downstaging may allow transplantation in patients initially outside the selection
      criteria and seems to improve the prognosis; it also provides information on
      tumor biology. The main peculiarity of the transplantation setting, when this is
      compared with other modalities of treatment, is the need for pharmacological
      immunosuppression: this is based on drugs that have been demonstrated to increase
      the risk of tumor development. As HCC is an aggressive malignancy,
      immunosuppression has to be handled carefully in patients who have HCC at the
      time of transplantation and new categories of immunosuppressive agents should be
      considered. Adjuvant chemotherapy following transplantation has failed to show
      any significant advantage. The aim of the present study is to review the possible
      strategies to avoid recurrence of HCC after liver transplantation based on the
      current clinical evidence and the more recent developments and to discuss
      possible future directions.

PMID- 22147975
TI  - Pancreatic metastases from renal cell carcinoma: the state of the art.
AB  - Pancreatic metastases are rare, with a reported incidence varying from 1.6% to
      11% in autopsy studies of patients with advanced malignancy. In clinical series,
      the frequency of pancreatic metastases ranges from 2% to 5% of all pancreatic
      malignant tumors. However, the pancreas is an elective site for metastases from
      carcinoma of the kidney and this peculiarity has been reported by several
      studies. The epidemiology, clinical presentation, and treatment of pancreatic
      metastases from renal cell carcinoma are known from single-institution case
      reports and literature reviews. There is currently very limited experience with
      the surgical resection of isolated pancreatic metastasis, and the role of surgery
      in the management of these patients has not been clearly defined. In fact, for
      many years pancreatic resections were associated with high rates of morbidity and
      mortality, and metastatic disease to the pancreas was considered to be a terminal
      stage condition. More recently, a significant reduction in the operative risk
      following major pancreatic surgery has been demonstrated, thus extending the
      indication for these operations to patients with metastatic disease.

PMID- 22147976
TI  - Spectrum of mucin-producing neoplastic conditions of the abdomen and pelvis:
      cross-sectional imaging evaluation.
AB  - Various mucin-producing neoplasms originate in different abdominal and pelvic
      organs. Mucinous neoplasms differ from non-mucinous neoplasms because of the
      differences in clinical outcome and imaging appearance. Mucinous carcinoma, in
      which at least 50% of the tumor is composed of large pools of extracellular mucin
      and columns of malignant cells, is associated with a worse prognosis. Signet ring
      cell carcinoma is characterized by large intracytoplasmic mucin vacuoles that
      expand in the malignant cells with the nucleus displaced to the periphery. Its
      prognosis is also generally poor. In contrast, intraductal papillary mucinous
      neoplasm of the bile duct and pancreas, which is characterized by proliferation
      of ductal epithelium and variable mucin production, has a better prognosis than
      other malignancies in the pancreaticobiliary tree. Imaging modalities play a
      critical role in differentiating mucinous from non-mucinous neoplasms. Due to
      high water content, mucin has a similar appearance to water on ultrasound (US),
      computed tomography (CT), and magnetic resonance imaging, except when thick and
      proteinaceous, and then it tends to be hypoechoic with fine internal echoes or
      have complex echogenicity on US, hyperdense on CT, and hyperintense on T1- and
      hypointense on T2-weighted images, compared to water. Therefore, knowledge of
      characteristic mucin imaging features is helpful to diagnose various mucin
      producing neoplastic conditions and to facilitate appropriate treatment.

PMID- 22147977
TI  - Lipopolysaccharide induces and activates the Nalp3 inflammasome in the liver.
AB  - AIM: To examine the activation of the Nalp3 inflammasome and its downstream
      targets following lipopolysaccharide (LPS)-induced stimulation in the liver.
      METHODS: Six-to-eight-week-old C57BL/6 chow fed mice were injected
      intraperitoneally with 0.5 MUg/g bodyweight LPS and sacrificed 2, 4, 6, 18 or 24
      h later. LPS-induced liver damage was confirmed by a biochemical assay to detect
      alanine aminotransferase (ALT) levels. To determine if LPS stimulation in the
      liver led to activation of the inflammasome, real-time quantitative polymerase
      chain reaction was used to evaluate the mRNA expression of components of the
      Nalp3 inflammasome. Enzyme-linked immunosorbent assays were used to determine the
      protein expression levels of several downstream targets of the Nalp3
      inflammasome, including caspase-1 and two cytokine targets of caspase-1,
      interleukin (IL)-1beta and IL-18. RESULTS: We found that LPS injection resulted
      in liver damage as indicated by elevated ALT levels. This was associated with a
      significant increase in both mRNA and protein levels of the proinflammatory
      cytokine tumor necrosis factor (TNF)-alpha in the liver, as well as increased
      levels of TNFs in serum. We showed that LPS stimulation led to upregulation of
      mRNA levels in the liver for all the receptor components of the inflammasome,
      including Nalp3, Nalp1, pannexin-1 and the adaptor molecule apoptosis-associated
      speck-like, caspase recruitment domain-domain containing protein. We also found
      increased levels of mRNA and protein for caspase-1, a downstream target of the
      inflammasome. In addition, LPS challenge led to increased levels of both mRNA and
      protein in the liver for two cytokine targets of caspase-1, IL-1beta and IL-18.
      Interestingly, substantial baseline expression of pre-IL-1beta and pre-IL-18 was
      found in the liver. Inflammasome and caspase-1 activation was indicated by the
      significant increase in the active forms of IL-1beta and IL-18 after LPS
      stimulation. CONCLUSION: Our results show that the Nalp3 inflammasome is
      upregulated and activated in the liver in response to LPS stimulation.

PMID- 22147978
TI  - Autophagy-related proteins Beclin-1 and LC3 predict cetuximab efficacy in
      advanced colorectal cancer.
AB  - AIM: To investigate the utility of Beclin-1 and LC3, two autophagy-related
      proteins, in predicting the cetuximab efficacy in advanced colorectal cancer
      (ACRC). METHODS: The data of 85 patients with ACRC treated at the Sun Yat-sen
      University Cancer Center from March 1, 2005 to December 31, 2008 were studied,
      including 45 cases treated with cetuximab-containing chemotherapy and 40 cases
      treated with non-cetuximab-containing chemotherapy. Beclin-1 and LC3 expression
      was evaluated by immunohistochemistry, and KRAS status was evaluated by
      polymerase chain reaction. RESULTS: Beclin-1 and LC3 expression in ACRC was
      significantly correlated (r = 0.44, P < 0.01); however, LC3 was more highly
      expressed in cancerous tissues than in normal tissues (Z = -2.63, P < 0.01). In
      the cetuximab-containing chemotherapy group, patients with low LC3 expression had
      higher objective response rates (ORRs) than those with high LC3 expression (52.9%
      vs 17.9%, P = 0.01), and patients with low Beclin-1 expression had a longer
      median progression-free survival (PFS) than their counterparts with higher Beclin
      1 expression (9.0 mo vs 3.0 mo, P = 0.01). However, neither of these predictive
      relationships was detected in the group treated with non-cetuximab-containing
      chemotherapy. Patients with wild-type KRAS had higher ORRs (42.3% vs 9.1%, P =
      0.049) and disease control rates (DCRs) (73.1% vs 36.4%, P = 0.035), and longer
      median PFS (5.5 mo vs 2.5 mo, P = 0.02) than those with mutant KRAS in the
      cetuximab-containing chemotherapy group. Neither Beclin-1 (P = 0.52) nor LC3 (P =
      0.32) expression was significantly correlated with KRAS status. CONCLUSION:
      Patients with low Beclin-1 expression had a longer PFS than those with high
      Beclin-1 expression, and patients with low LC3 expression had a higher ORR in
      ACRC patients treated with cetuximab-containing chemotherapy.

PMID- 22147979
TI  - Early experience of the compression anastomosis ring (CARTM 27) in left-sided
      colon resection.
AB  - AIM: To evaluate clinical validity of the compression anastomosis ring (CARTM 27)
      anastomosis in left-sided colonic resection. METHODS: A non-randomized
      prospective data collection was performed for patients undergoing an elective
      left-sided colon resection, followed by an anastomosis using the CARTM 27 between
      November 2009 and January 2011. Eligibility criteria of the use of the CARTM 27
      were anastomoses between the colon and at or above the intraperitoneal rectum.
      The primary short-term clinical endpoint, rate of anastomotic leakage, and other
      clinical outcomes, including intra- and postoperative complications, length of
      operation time and hospital stay, and the ring elimination time were evaluated.
      RESULTS: A total of 79 patients (male, 43; median age, 64 years) underwent an
      elective left-sided colon resection, followed by an anastomosis using the CARTM
      27. Colectomy was performed laparoscopically in 70 patients, in whom two patients
      converted to open procedure (2.9%). There was no surgical mortality. As an
      intraoperative complication, total disruption of the anastomosis occurred by
      premature enforced tension on the proximal segment of the anastomosis in one
      patient. The ring was removed and another new CARTM 27 anastomosis was
      constructed. One patient with sigmoid colon cancer showed postoperative
      anastomotic leakage after 6 d postoperatively and temporary diverting ileostomy
      was performed. Exact date of expulsion of the ring could not be recorded because
      most patients were not aware that the ring had been expelled. No patients
      manifested clinical symptoms of anastomotic stricture. CONCLUSION: Short-term
      evaluation of the CARTM 27 anastomosis in elective left colectomy suggested it to
      be a safe and efficacious alternative to the standard hand-sewn or stapling
      technique.

PMID- 22147980
TI  - Analysis of ABC (D) stratification for screening patients with gastric cancer.
AB  - AIM: To evaluate the value of ABC (D) stratification [combination of serum
      pepsinogen and Helicobacter pylori (H. pylori) antibody] of patients with gastric
      cancer. METHODS: Ninety-five consecutive patients with gastric cancer were
      enrolled into the study. The serum pepsinogen I (PG I)/pepsinogen II (PG II) and
      H. pylori antibody levels were measured. Patients were classified into five
      groups of ABC (D) stratification according to their serological status.
      Endoscopic findings of atrophic gastritis and histological differentiation were
      also analyzed in relation to the ABC (D) stratification. RESULTS: The mean
      patient age was (67.9 +/- 8.9) years. Three patients (3.2%) were classified into
      group A, 7 patients (7.4%) into group A', 27 patients (28.4%) into group B, 54
      patients (56.8%) into group C, and 4 patients (4.2%) into group D, respectively.
      There were only three cases in group A when the patients taking acid proton pump
      inhibitors and those who had undergone eradication therapy for H. pylori (group
      A') were excluded. These three cases had mucosal atrophy in the grey zone
      according to the diagnostic manual of ABC (D) stratification. Histologically, the
      mean age of the patients with well differentiated adenocarcinoma was
      significantly higher than that of the patients with poorly differentiated
      adenocarcinoma (P < 0.05). There were no differences in the pattern of atrophy in
      the endoscopies between the well differentiated and poorly differentiated groups.
      CONCLUSION: ABC (D) stratification is a good method for screening patients with
      gastric cancers. Endoscopy is needed for grey zone cases to check the extent of
      mucosal atrophy.

PMID- 22147981
TI  - Morphological effects of autoclaved diet on the myenteric neurons of rats.
AB  - AIM: To evaluate the effect of autoclaved diet on the jejunum neurons of the
      myenteric plexus of rats during their growth. METHODS: The experimental groups
      were made up of rats going through weaning whose mothers received either an
      autoclaved or a non-autoclaved diet during gestation and lactation, and rats that
      were fed the same diet as their mothers during the post-weaning period. In order
      to measure the neurons' body profile and to quantify the number of neurons per
      area, preparations were stained by the nicotinamide adenine dinucleotide
      diaphorase method. RESULTS: No significant changes were observed in rats' body
      weight or in the number of neurons regardless of the diet used (P > 0.05). There
      was a decrease in the jejunum-ileum length in rats treated with an autoclaved
      diet (P < 0.05). An increase in the neuronal cross-sectional area was seen in
      rats that had received the autoclaved diet, an effect that was significant for
      animals undergoing weaning. In addition, all observed factors showed significant
      differences when related to the age of the animals. CONCLUSION: The autoclaved
      diet did not alter the quantity of neurons, but increased their cell body area,
      suggesting changes similar to those observed in protein deficiency.

PMID- 22147982
TI  - De novo combination therapy with lamivudine and adefovir dipivoxil in chronic
      hepatitis B patients.
AB  - AIM: To investigate the appropriate time for combination therapy in HBeAg
      positive chronic hepatitis B (CHB) patients with decompensated cirrhosis.
      METHODS: Thirty HBeAg positive CHB patients with decompensated cirrhosis were
      enrolled in the study. All of the patients were given 48 wk combination therapy
      with lamivudine (LAM) and adefovir dipivoxil (ADV). Briefly, 10 patients were
      given the de novo combination therapy with LAM and ADV, whereas the other 20
      patients received ADV in addition to LAM after hepatitis B virus (HBV) genetic
      mutation. RESULTS: Serum alanine aminotransferase and total bilirubin were both
      improved in the two groups at 4, 12, 24 and 48 wk after treatment. Serum albumin
      was also improved at 24 and 48 wk after combination therapy in both groups. The
      serum HBV DNA level was still detectable in every patient in the two groups at 4
      and 12 wk after combination treatment. However, in the de novo combination group,
      serum HBV DNA levels in 4 (40%) and 9 (90%) patients was decreased to below
      1*10(3) copies/mL at 24 and 48 wk after the combination treatment, respectively.
      In parallel, serum HBV DNA levels in 2 (20%) and 8 (40%) patients in the add-on
      combination group became undetectable at 24 and 48 wk after combination
      treatment, respectively. Furthermore, 6 (60%) patients in the de novo combination
      group achieved HBeAg seroconversion after 48 wk treatment, whereas only 4 (20%)
      patients in the add-on combination group achieved seroconversion. Child-Pugh
      score of patients in the de novo combination group was better than that of
      patients in the add-on combination group after 48 wk treatment. Moreover,
      patients in the de novo combination group had a significantly decreased serum
      creatinine level and elevated red blood cell counts. CONCLUSION: De novo
      combination therapy with LAM and ADV was better than add-on combination therapy
      in terms of Child-Pugh score, virus inhibition and renal function.

PMID- 22147983
TI  - Schistosoma japonicum ova maintains epithelial barrier function during
      experimental colitis.
AB  - AIM: To evaluate the impacts of Schistosoma japonicum (S. japonicum) ova on the
      tight junction barriers in a trinitrobenzenesulfonic acid (TNBS)-induced colitis
      model. METHODS: Balb/c mice were randomly divided into three groups: control
      group; TNBS(+)ova(-) group and TNBS(+)ova(+) group. TNBS was used intracolonic to
      induce colitis and mice of the TNBS(+)ova(+) group were pre-exposed to S.
      japonicum ova as a prophylactic intervention. Colon inflammation was quantified
      using following variables: mouse mortality, weight loss, colon extent and
      microscopic inflammation score. Serum expression of tumor necrosis factor-alpha
      and interferon-gamma were assessed to evaluate the systemic inflammatory
      response. NOD2 and its mRNA were also tested. Bacterial translocations were
      tested by culturing blood and several tissues. ZO-1 and occludin were chosen as
      the representations of tight junction proteins. Both the proteins and mRNA were
      assessed. RESULTS: Ova pre-treatment contributed to the relief of colitis and
      decreased the mortality of the models. NOD2 expression was significantly
      downregulated when pretreated with the ova. The TNBS injection caused a
      significant downregulation of ZO-1 and occludin mRNA together with their proteins
      in the colon; ova pre-exposure reversed these alterations. Treatment with S.
      japonicum ova in the colitis model caused lower intestinal bacterial
      translocation frequency. CONCLUSION: S. japonicum ova can maintain epithelial
      barrier function through increasing tight junction proteins, thus causing less
      exposure of NOD2 to the luminal antigens which may activate a series of
      inflammatory factors and induce colitis.

PMID- 22147984
TI  - A special recurrent pattern in small hepatocellular carcinoma after treatment:
      bile duct tumor thrombus formation.
AB  - AIM: To investigate the clinicopathologic features of bile duct tumor thrombus
      (BDTT) occurrence after treatment of primary small hepatocellular carcinoma
      (sHCC). METHODS: A total of 423 patients with primary sHCC admitted to our
      hospital underwent surgical resection or local ablation. During follow-up, only
      six patients were hospitalized due to obstructive jaundice, which occurred 5-76
      mo after initial treatment. The clinicopathologic features of these six patients
      were reviewed. RESULTS: Six patients underwent hepatic resection (n = 5) or radio
      frequency ablation (n = 1) due to primary sHCC. Five cases had an R1 resection
      margin, and one case had an ablative margin less than 5.0 mm. No vascular
      infiltration, microsatellites or bile duct/canaliculus affection was noted in the
      initial resected specimens. During the follow-up, imaging studies revealed a
      macroscopic BDTT extending to the common bile duct in all six patients. Four
      patients had a concomitant intrahepatic recurrent tumor. Surgical re-resection of
      intrahepatic recurrent tumors and removal of BDTTs (n = 4), BDTT removal through
      choledochotomy (n = 1), and conservative treatment (n = 1) was performed.
      Microscopic portal vein invasion was noted in three of the four resected
      specimens. All six patients died, with a mean survival of 11 mo after BDTT
      removal or conservative treatment. CONCLUSION: BDTT occurrence is a rare, special
      recurrent pattern of primary sHCC. Patients with BDTTs extending to the common
      bile duct usually have an unfavorable prognosis even following aggressive
      surgery. Insufficient resection or ablative margins against primary sHCC may be a
      risk factor for BDTT development.

PMID- 22147985
TI  - Effects of CpG-ODNs on phenotype and function of monocyte-derived dendritic cells
      in chronic hepatitis B.
AB  - AIM: To study the effects of synthetic nonmethylated CpG-containing
      oligodeoxynucleotides (CpG-ODNs), either alone or combined with recombinant
      Hepatitis B surface antigen (HBsAg) polypeptide, on the phenotype, function, and
      intracellular signaling pathways of monocyte-derived dendritic cells (DCs) in
      patients with chronic hepatitis B (CHB). METHODS: Peripheral blood monocytes
      isolated from CHB patients and healthy volunteers were induced to be dendritic
      cells by recombinant human granulocyte-monocyte colony stimulating factor and
      interleukin-4. The DCs were then treated with CpG-ODNs, CpG-ODNs/HBsAg, or tumor
      necrosis factor (TNF)-alpha for 18 h. The expression of surface molecules
      including HLA-DR, CD86, and CD1a in DCs were detected by flow cytometry, and the
      expression of signal transducers and activators of transcription (STAT1, 3, 4, 5,
      6) and suppressors of cell signaling (SOCS1, 3) were determined by Western
      blotting assay. In addition, the capacity of DCs to stimulate allogeneic T
      lymphocytes and the amount of IL-12p70 released from DCs were measured. RESULTS:
      In the DCs derived from patients with CHB, treatment with TNF-alpha, CpG-ODNs, or
      CpG-ODNs/HBsAg, as compared to the vector control, significantly increased the
      expression of HLA-DR, stimulated the release of IL-12p70, and enhanced the
      capacity of DCs to stimulate allogenic T lymphocytes. The expressions of
      STAT1/4/6 and SOCS1/3, but not STAT3/5, were upregulated by TNF-alpha, CpG-ODNs,
      and CpG-ODNs/HBsAg. In addition, the expression of CD1a was upregulated only in
      the presence of both CpG-ODNs and HBsAg. CONCLUSION: The treatment with CpG-ODNs,
      either alone or combined with HBsAg, has a remarkable stimulatory effect on the
      impaired phenotype and function of DCs in CHB, possibly by regulating the
      expression of STAT1, 4, 6 and SOCS1, 3.

PMID- 22147986
TI  - Simultaneous large cell neuroendocrine carcinoma and adenocarcinoma of the
      stomach.
AB  - A large cell neuroendocrine carcinoma (LCNEC) of the stomach is very rare. A 76
      year-old Japanese man was admitted to our hospital because of epigastralgia and
      nausea. Endoscopy revealed 2 large tumors in the stomach. He did not have
      multiple endocrine neoplasia type I or Zollinger-Ellison syndrome. Imaging
      modalities, including computed tomography and magnetic resonance imaging,
      revealed no other tumors. Gastrectomy, cholecystectomy, and lymph node dissection
      were performed. The resected stomach had 2 tumors: one was an antral ulcerated
      type 3 tumor measuring 5 cm x 5 cm, and the other was a polypoid type 1 tumor
      measuring 6 cm x 6 cm x 3 cm in the fundus. Microscopically, the antral ulcerated
      tumor was a well differentiated adenocarcinoma with deep invasion. The fundus
      polypoid tumor was a LCNEC, being composed of malignant large cells arranged in
      trabecular and nested patterns. The tumor cells were large and the nuclei were
      vesicular. Nucleoli were frequently present, and there were many mitotic figures,
      apoptotic bodies, and necrotic areas. Much lymphovascular permeation was seen.
      Seven out of 29 dissected lymph nodes showed metastatic foci; 6 were from the
      LCNEC and 1 from the adenocarcinoma. Many intravascular tumor emboli of LCNEC
      were seen in the peritoneum around the lymph nodes. Mucins were present in the
      adenocarcinoma but not in the LCNEC. Immunohistochemically, the LCNEC tumor cells
      were positive for pancytokeratins, synaptophysin (50% positive), chromogranin A
      (10% positive), Ki-67 (90% labeled), and platelet-derived growth factor-alpha
      (80% positive). They were negative for KIT, p53, CD56, and neuron-specific
      enolase. The non-cancerous stomach showed a normal number of endocrine cells. The
      patient is now treated with adjuvant chemotherapy.

PMID- 22147987
TI  - Lipomatous hemangiopericytoma of the stomach: a case report and a review of
      literature.
AB  - Lipomatous hemangiopericytomas (LHPCs) are rare soft-tissue tumors that are
      histologically characterized by hemangiopericytomatous vasculature and the
      presence of mature adipocytes. We present the clinicopathological features of a
      case of gastric LHPC in a 56-year-old female, along with a literature review.
      Endoscopy and endoscopic ultrasound showed a submucosal tumor 0.8 cm across in
      the greatest dimension in the lesser curvature side of the gastric antrum.
      Grossly, the well-defined mass had a solid and tan-white cut surface admixed with
      myxoid regions and yellowish areas. Histological examination revealed a
      submucosal well-circumscribed lesion composed of cellular nodules with the
      classic appearance of an hemangiopericytoma admixed with clusters and lobules of
      mature adipocytes. The ill-defined tumor cells had weakly eosinophilic cytoplasm
      and contained spindled nuclei with occasional small nucleoli. Nuclei atypia and
      mitoses were absent, and no cellular atypia, necrosis or vascular invasion was
      observed. Immunohistochemistry showed that the tumor cells were diffusely
      positive for CD34, CD99, and vimentin and were focally reactive for bcl-2. This
      is the first known report of an LHPC in the stomach. The patient was followed for
      12 mo without any evidence of metastasis or recurrence.

PMID- 22147988
TI  - Socioeconomic costs of overweight and obesity in Korean adults.
AB  - This study was conducted to estimate the socioeconomic costs of overweight and
      obesity in a sample of Korean adults aged 20 yr and older in 2005. The
      socioeconomic costs of overweight and obesity include direct costs (inpatient
      care, outpatient care and medication) and indirect costs (loss of productivity
      due to premature deaths and inpatient care, time costs, traffic costs and nursing
      fees). Hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease,
      stroke, colon cancer and osteoarthritis were selected as obesity-related
      diseases. The population attributable fraction (PAF) of obesity was calculated
      from national representative data of Korea such as the National Health Insurance
      Corporation (NHIC) cohort data and the 2005 Korea National Health and Nutrition
      Examination Survey (KNHANES) data. Direct costs of overweight and obesity were
      estimated at approximately U$1,081 million equivalent (men: U$497 million, women:
      U$584 million) and indirect costs were estimated at approximately U$706 million
      (men: U$527 million, women: U$178 million). The estimated total socioeconomic
      costs of overweight and obesity were approximately U$1,787 million (men: U$1,081
      million, women: U$706 million). These total costs represented about 0.22% of the
      gross domestic product (GDP) and 3.7% of the national health care expenditures in
      2005. We found the socioeconomic costs of overweight and obesity in Korean adults
      aged 20 yr and older are substantial. In order to control the socioeconomic
      burden attributable to overweight and obesity, effective national strategies for
      prevention and management of obesity should be established and implemented.

PMID- 22147989
TI  - Association between body mass index and asthma symptoms among Korean children: a
      nation-wide study.
AB  - The purpose of this study was to investigate the association between body mass
      index (BMI) and the prevalence of wheeze using nation-wide cross-sectional study
      in Korean children. Total 50,200 children from 427 elementary schools were
      randomly selected according to residential areas (metropolitan, provincial,
      rural, and industrial areas) by the cluster sampling method. The International
      Study of Asthma and Allergies in Childhood (ISAAC) questionnaires were used to
      measure the prevalence of wheeze. Among 31,026 respondents, 25,322 were analyzed.
      BMI was classified into quartiles based on BMI-for-age percentile. In all
      residential areas, pets at home and visible mold or moisture were associated with
      an increased prevalence of wheeze in both genders. However, other living
      environment factors were not consistently associated among residential areas and
      gender. Among girls, lowest BMI was negatively associated with prevalence of
      wheeze and highest BMI was positively associated in all residential areas. In
      multilevel logistic regression analysis, environmental tobacco smoking exposure,
      pets at home, visible mold or moisture, and being in the lowest and highest BMI
      quartile were significantly associated with the prevalence of wheeze in both
      genders. BMI has become an important risk factor for asthma symptoms among Korean
      children.

PMID- 22147990
TI  - Hematopoietic stem cell transplantation in children with leukemia: a single
      institution experience with respect to donors.
AB  - Aim of this study was to compare the outcomes of transplantation by donor source
      and to help select the best alternative donor in children with leukemia. Donor
      sources included matched related donor (MRD, n = 35), allele-matched unrelated
      donor (M-UD, n = 10) or -mismatched (MM)-UD (n = 13) or unrelated umbilical cord
      blood (UCB, n = 11). UCB group had a significantly higher incidence of grade II
      IV acute graft versus host disease (MRD, 11.8%; M-UD, 30.0%; MM-UD, 15.4%, UCB,
      54.4%, P = 0.004) but there was no difference in incidence of chronic graft
      versus host disease between 4 groups. The 5-yr leukemia-free survival (LFS) was
      76.7%, 60.0%, 69.2%, and 45.5%, respectively (P = 0.128). MRD group showed higher
      LFS rate than UCB group (P = 0.022). However, LFS of M-UD and MM-UD together
      (65.2%) was not different from that of MRD group (76.7%, P = 0.325), or from that
      of UCB (45.5%, P = 0.190). The relapse incidence at 5 yr was 17.1%, 20.0%, 15.4%,
      and 0%, respectively (P = 0.460). The 100-day treatment-related mortality was
      2.9%, 20.0%, 7.7%, and 36.4%, respectively (P = 0.011). Despite the limitations
      of small number of patients, unrelated donor transplants including even allele
      mismatched ones, seem to be as effective in children with leukemia lacking
      suitable relative donors. Also, UCB transplant may serve as another possible
      option in urgent transplants.

PMID- 22147991
TI  - Prognostic value of immunohistochemical biomarkers at different cut-off values in
      patients with diffuse large B-cell lymphoma treated with CHOP chemotherapy.
AB  - Many predictive models have been proposed for better stratification of diffuse
      large B-cell lymphoma (DLBCL). Hans' algorithm has been widely used as standard
      to sub-classify DLBCL into germinal center B-cell (GCB) and non-GCB origins.
      However, there have been disagreements in the literature regarding its prognostic
      significance. Here, we retrospectively analyzed Hans' algorithm and the
      individual immunohistochemical biomarkers at different cut-off values (5%, 30%,
      50% or 75%) in 94 Korean patients with DLBCL treated with combination
      chemotherapy with cyclophosphamide, daunorubicin, vincristine, and prednisone. No
      significant differences were observed between the GCB (18 patients, 19.1%) and
      non-GCB (76, 80.9%) groups. Among individual biomarkers, CD10 negativity (cut
      point: 30%) and bcl-6 positivity (cut point: 5%) were independent good prognostic
      markers in progression-free survival (PFS), whereas bcl-6 (cut point: 5%)
      positivity was an independent good prognostic marker in overall survival
      irrelevant of international prognostic index. The present study showed the lack
      of predictability of Hans' algorithm in DLBCL patients, and that CD10, Bcl-6 may
      have diverse prognostic significance at different cut-off values. Our results
      suggest that the proposed cut-off value may not be applied universally, and that
      the optimal cut-off value may need to be optimized for individual laboratory.

PMID- 22147992
TI  - Novel EGFR-TK inhibitor EKB-569 inhibits hepatocellular carcinoma cell
      proliferation by AKT and MAPK pathways.
AB  - Epidermal growth factor receptor (EGFR)-targeted therapies have been effective in
      some cancers, but not in hepatocellular carcinoma (HCC). The aim of this study
      was to investigate the drug potential to overcome multi-drug resistance in HCC
      cells. Thirteen drug-sensitive HCC cells were assessed using the CCK-8 assay.
      G(0)-G(1) arrest was measured by FACS. Western blot analysis was used to detect
      the key enzymes in both the Ras/Raf and PI3K pathways. When establishing the
      IC(50) of HCC to several drugs, including EKB-569, sorafenib, erlotinib,
      gefitinib, pazopanib, and brivanib, SK-Hep1 cells treated with EKB-569 have shown
      the highest (72.8%-86.4%) G(0)-G(1) arrest and decreased the phosphorylation of
      AKT and ERK at the protein level. We found that EKB-569 had higher efficacy in
      HCC, compared to first generation, reversible EGFR-TK inhibitors. Furthermore,
      the combination of sorafenib and EKB-569 showed a synergistic effect to inhibit
      proliferation of SNU-475, previously the most resistant cell to EGFR-TKIs.
      Therefore, novel EKB-569 in combination with sorafenib may be able to overcome
      HCC resistance to EGFR-TK inhibitors.

PMID- 22147993
TI  - Preventive effects of zoledronic acid on bone metastasis in mice injected with
      human breast cancer cells.
AB  - Bisphosphonates are used routinely to reduce bone-related events in breast cancer
      patients with bone metastasis. We evaluated the effects of zoledronic acid, a
      third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis
      in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice
      either simultaneously or after intracardiac injection of human breast cancer MDA
      MB-231 cells. Nude mice treated with zoledronic acid at early time points showed
      a lower incidence of bone metastases than did vehicle-treated nude mice, but
      these differences were not statistically significant. Only 37.5% of mice treated
      with zoledronic acid at the time of tumor cell inoculation developed bone
      metastases compared to over 51.8% of mice receiving vehicle alone (P = 0.304).
      Cell count of apoptosis confirmed by immunohistochemical staining in metastatic
      bone tissue significantly increased in the zoledronic acid-treated groups
      compared to non-treated group (1,018.3 vs 282.0; P = 0.046). However, metastatic
      tumor cells, which invade soft tissue around the bone, did not show extensive
      apoptosis; there were no differences between the zoledronic acid-treated and
      control groups. These results suggest that zoledronic acid increases apoptosis of
      metastatic breast tumor cells in the bone and could therefore reduce metastatic
      tumor burden. These results support the use of zoledronic acid to reduce the
      incidence of bone metastasis in breast cancer.

PMID- 22147994
TI  - Role of the alternans of action potential duration and aconitine-induced
      arrhythmias in isolated rabbit hearts.
AB  - Under conditions of Na(+) channel hyperactivation with aconitine, the changes in
      action potential duration (APD) and the restitution characteristics have not been
      well defined in the context of aconitine-induced arrhythmogenesis. Optical
      mapping of voltage using RH237 was performed with eight extracted rabbit hearts
      that were perfused using the Langendorff system. The characteristics of APD
      restitution were assessed using the steady-state pacing protocol at baseline and
      0.1 uM aconitine concentration. In addition, pseudo-ECG was analyzed at baseline,
      and with 0.1 and 1.0 uM of aconitine infusion respectively. Triggered activity
      was not shown in dose of 0.1 uM aconitine but overtly presented in 1.0 uM of
      aconitine. The slopes of the dynamic APD restitution curves were significantly
      steeper with 0.1 uM of aconitine than at baseline. With aconitine administration,
      the cycle length of initiation of APD alternans was significantly longer than at
      baseline (287.5 +/- 9.6 vs 247.5 +/- 15.0 msec, P = 0.016). The functional
      reentry following regional conduction block appears with the progression of APD
      alternans. Ventricular fibrillation is induced reproducibly at pacing cycle
      length showing a 2:1 conduction block. Low-dose aconitine produces
      arrhythmogenesis at an increasing restitution slope with APD alternans as well as
      regional conduction block that proceeds to functional reentry.

PMID- 22147995
TI  - Long-term echocardiographic follow-up after posterior mitral annuloplasty using a
      vascular strip for ischemic mitral regurgitation: ten-years of experience at a
      single center.
AB  - Management of ischemic mitral regurgitation (MR) is challenging. The aim of this
      study was to investigate long-term clinical and echocardiographic results of
      restrictive mitral annuloplasty for ischemic MR. From 2001 through 2010, 96
      patients who underwent myocardial revascularization with restrictive mitral
      annuloplasty using a vascular strip for ischemic MR were analyzed. Patients were
      stratified into two groups based on left ventricular ejection fraction (LVEF):
      group I, n = 50, with LVEF > 35% and group II, n = 46, with LVEF <= 35%. The
      early mortality rate was 2.1% (2/96) and the late cardiac mortality rate was
      11.5% (11/96). MR grade was reduced at discharge (0.8 +/- 0.7) but increased
      during follow-up (1.1 +/- 0.8, P = 0.001). There was no intergroup difference in
      terms of freedom from recurrent MR >= moderate eight years after surgery (94.1%
      +/- 5.7%, group I vs 87.8% +/- 7.2%, group II; P = 0.575). NYHA functional class
      (odds ratio [OR], 2.2; P = 0.044) and early postoperative residual MR >= mild
      (OR, 25.4; P < 0.001) were independent predictors of recurrent MR. Restrictive
      mitral annuloplasty using a vascular strip is effective in ischemic MR. It is
      important to avoid early postoperative residual MR.

PMID- 22147996
TI  - Theoretical estimation of cannulation methods for left ventricular assist device
      support as a bridge to recovery.
AB  - Left ventricular assist device (LVAD) support under cannulation connected from
      the left atrium to the aorta (LA-AA) is used as a bridge to recovery in heart
      failure patients because it is non-invasive to ventricular muscle. However, it
      has serious problems, such as valve stenosis and blood thrombosis due to the low
      ejection fraction of the ventricle. We theoretically estimated the effect of the
      in-series cannulation, connected from ascending aorta to descending aorta (AA
      DA), on ventricular unloading as an alternative to the LA-AA method. We developed
      a theoretical model of a LVAD-implanted cardiovascular system that included
      coronary circulation. Using this model, we compared hemodynamic responses
      according to various cannulation methods such as LA-AA, AA-DA, and a cannulation
      connected from the left ventricle to ascending aorta (LV-AA), under continuous
      and pulsatile LVAD supports. The AA-DA method provided 14% and 18% less left
      ventricular peak pressure than the LA-AA method under continuous and pulsatile
      LVAD conditions, respectively. The LA-AA method demonstrated higher coronary flow
      than AA-DA method. Therefore, the LA-AA method is more advantageous in increasing
      ventricular unloading whereas the AA-DA method is a better choice to increase
      coronary perfusion.

PMID- 22147997
TI  - Characteristics of body fat, body fat percentage and other body composition for
      Koreans from KNHANES IV.
AB  - Accurate measurement of fat mass has become increasingly important with the
      increasing incidence of obesity. We assessed fat and muscle mass of Koreans with
      the Korea National Health and Nutrition Examination Survey IV (KNHANES IV). We
      studied 10,456 subjects (aged 20 to 85 yr; 4,476 men, 5,980 women). Fat and
      muscle mass were measured by dual-energy x-ray absorptiometry. Reference values
      of body compositions were obtained using the LMS method. The fat mass index (FMI,
      body fat mass/height(2); kg/m(2)) of Korean men did not correlate with age (P =
      0.452), but those of Korean women (P < 0.001) did. The ratio of percentage of fat
      in the trunk and legs was positively related with age in both the genders. The
      appendicular lean mass/height(2) (kg/m(2)) of Korean men was negatively related
      to age (P < 0.001). In women, this ratio increased with age (P < 0.001). When we
      defined obesity according to the FMI classification, the rates of obesity were
      6.1% (FMI > 9 kg/m(2)) in men and 2.7% (FMI > 13 kg/m(2)) in women. It is
      concluded that the muscle mass decreases and obesity increases with aging in
      Korean men, whereas both fat mass and obesity increase with aging in Korean
      women.

PMID- 22147999
TI  - Practice pattern of gastroenterologists for the management of GERD under the
      minimal influence of the insurance reimbursement guideline: a multicenter
      prospective observational study.
AB  - The objective of the study was to document practice pattern of
      gastroenterologists for the management of gastroesophageal reflux disease (GERD)
      under the minimal influence of the insurance reimbursement guideline. Data on
      management for 1,197 consecutive patients with typical GERD symptoms were
      prospectively collected during 16 weeks. In order to minimize the influence of
      reimbursement guideline on the use of proton pump inhibitors (PPIs), rabeprazole
      was used for the PPI treatment. A total of 861 patients (72%) underwent endoscopy
      before the start of treatment. PPIs were most commonly prescribed (87%). At the
      start of treatment, rabeprazole 20 mg daily was prescribed to 94% of the patients
      who received PPI treatment and 10 mg daily to the remaining 6%. At the third
      visits, rabeprazole 20 mg daily was prescribed to 70% of those who were followed
      and 10 mg daily for the remaining 30%. Continuous PPI treatment during the 16
      week period was performed in 63% of the study patients. In conclusion, a full
      dose PPI is preferred for the initial and maintenance treatment of GERD under the
      minimal influence of the insurance reimbursement guideline, which may reflect a
      high proportion of GERD patients requiring a long-term treatment of a full-dose
      PPI.

PMID- 22147998
TI  - Comparison of clinico-physiologic and CT imaging risk factors for COPD
      exacerbation.
AB  - To date, clinico-physiologic indices have not been compared with quantitative CT
      imaging indices in determining the risk of chronic obstructive pulmonary disease
      (COPD) exacerbation. We therefore compared clinico-physiologic and CT imaging
      indices as risk factors for COPD exacerbation in patients with COPD. We
      retrospectively analyzed 260 COPD patients from pulmonary clinics at 11 hospitals
      in Korea from June 2005 to November 2009 and followed-up for at least one year.
      At the time of enrollment, none of these patients had COPD exacerbations for at
      least 2 months. All underwent clinico-physiologic and radiological evaluation for
      risk factors of COPD exacerbation. After 1 yr, 106 of the 260 patients had at
      least one exacerbation of COPD. Multiple logistic regression analysis showed that
      old age, high Charlson Index, and low FEV(1) were significant in a clinico
      physiologic model, with C-statistics of 0.69, and that increased age and
      emphysema index were significant in a radiologic model, with C-statistics of
      0.64. The difference between the two models was statistically significant (P =
      0.04 by bootstrap analysis). Combinations of clinico-physiologic risk factors may
      be better than those of imaging risk factors in predicting COPD exacerbation.

PMID- 22148000
TI  - Korean-specific parameter models for calculating the risk of Down syndrome in the
      second trimester of pregnancy.
AB  - The purpose of the current study was to propose a Korean-specific parameter set
      for calculating the risk of Down syndrome in the second trimester of pregnancy
      and to determine the screening performances of triple and quadruple tests in
      Korean women. Using the data on triple or quadruple screening from three
      hospitals in Korea during 7 yr, we re-converted the concentrations of four serum
      markers to multiple of median values according to gestational age and maternal
      weight. After re-calculating the risk of Down syndrome in each pregnancy by
      multiplying maternal age-specific risk by the likelihood ratio values for the
      serum markers, screening performances and optimal cut-off values of triple and
      quadruple tests were analyzed. Among 16,077 pregnancies, 23 cases had Down
      syndrome (1.4/1,000 deliveries). Compared to the previous program, the tests with
      new parameters had improved screening performance. The triple and quadruple tests
      had detection rates of 65.2% and 72.7%, respectively, at a false-positive rate of
      5%. The optimal cut-off value for the quadruple and triple tests was 1:250. We
      have presented a Korean-specific parameter set for Down syndrome screening. The
      proposed screening test using this parameter set may improve the performance of
      Down syndrome screening for Korean women.

PMID- 22148001
TI  - Little impact of antiplatelet agents on venous thromboembolism after hip fracture
      surgery.
AB  - Since the late 1980s, low dose aspirin has been used to prevent stroke and
      ischemic heart disease. However, prophylactic effect of antiplatelets against
      venous thromboembolism (VTE), in patients who undergo hip fracture surgery (HFS)
      is controversial. Our purpose was to determine the incidence of symptomatic VTE
      after HFS and to evaluate whether antiplatelets reduce the development of
      symptomatic VTE following HFS. We retrospectively reviewed 858 HFS in 824
      consecutive patients which were performed from May 2003 to April 2010 at an East
      Asian institute. We compared the incidence of symptomatic VTE in antiplatelet
      users and non-users using multivariate logistic regression analyses. Overall
      incidences of symptomatic pulmonary embolism including fatal pulmonary embolism,
      and symptomatic deep vein thrombosis in this study were 2.4% (21/858), and 3.5%
      (30/858), respectively. The incidence of symptomatic VTE was 4.8% (12/250) in
      antiplatelet users and 4.3% (26/608) in non-users (P = 0.718). It is suggested
      that antiplatelet agents are not effective in prevention of symptomatic VTE after
      HFS.

PMID- 22148002
TI  - An outbreak of trichinellosis with detection of Trichinella larvae in leftover
      wild boar meat.
AB  - The clinical diagnosis of trichinellosis can be difficult due to lack of
      pathognomonic signs or symptoms. In Korea, since the first report of human
      infection by Trichinella spiralis in 1997 following the consumption of raw badger
      meat, there have been occasional trichinellosis outbreaks. We describe an
      outbreak of 12 cases of trichinellosis in Korea and implicate raw wild boar meat
      as the culprit. A total of 27 larvae of Trichinella (0.54 larvae per gram of
      meat) were recovered from the leftover raw wild boar meat.

PMID- 22148003
TI  - Fatal rhabdomyolysis in a patient with liver cirrhosis after switching from
      simvastatin to fluvastatin.
AB  - HMG-CoA reductase inhibitors (statins) are widely used to treat
      hypercholesterolemia. Among the adverse effects associated with these drugs are
      statin-associated myopathies, ranging from asymptomatic elevation of serum
      creatine kinase to fatal rhabdomyolysis. Fluvastatin-induced fatal rhabdomyolysis
      has not been previously reported. We describe here a patient with liver cirrhosis
      who experienced fluvastatin-induced fatal rhabdomyolysis. This patient had been
      treated with simvastatin (20 mg/day) for coronary artery disease and was switched
      to fluvastatin (20 mg/day) 10 days before admission. He was also taking aspirin,
      betaxolol, candesartan, lactulose, and entecavir. Rhabdomyolysis was complicated
      and continued to progress. He was treated with massive hydration, urine
      alkalization, intravenous furosemide, and continuous renal replacement therapy
      for acute renal failure, but eventually died due to rhabdomyolysis complicated by
      hepatic failure. In conclusion, fluvastatin should be used with caution in
      patients with liver cirrhosis, especially with other medications metabolized with
      CYP2C9.

PMID- 22148004
TI  - Interferon-alpha-induced destructive thyroiditis followed by Graves' disease in a
      patient with chronic hepatitis C: a case report.
AB  - Interferon-induced thyroiditis (IIT) is a major clinical problem for patients
      receiving interferon-alpha (IFN-alpha) therapy. But, destructive thyroiditis
      followed by Graves' disease associated with IFN-alpha therapy is very rarely
      reported. Herein, we report a rare case of pegylated IFN-alpha (pegIFN-alpha)
      induced destructive thyroiditis followed by Graves' disease in a patient with HCV
      infection. A 31-yr-old woman suffered from chronic active hepatitis C and was
      treated with pegIFN-alpha and ribavirin for 12 months. Results of a thyroid
      function test and autoantibody levels were normal before IFN-alpha therapy was
      initiated. Destructive thyrotoxicosis appeared seven months after the initiation
      of IFN-alpha therapy, followed by Graves' thyrotoxicosis two months after the
      cessation of therapy. The diagnoses of destructive thyroiditis and Graves'
      disease were confirmed by the presence of TSH receptor antibodies in addition to
      Tc-99m scintigraphy findings. The patient's antithyroglobulin antibody titer
      increased gradually during IFN-alpha therapy and remained weakly positive after
      IFN-alpha therapy was discontinued.

PMID- 22148005
TI  - Hutchinson-Gilford progeria syndrome with G608G LMNA mutation.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare condition originally
      described by Hutchinson in 1886. Death result from cardiac complications in the
      majority of cases and usually occurs at average age of thirteen years. A 4-yr old
      boy had typical clinical findings such as short stature, craniofacial
      disproportion, alopecia, prominent scalp veins and sclerodermatous skin. This
      abnormal appearance began at age of 1 yr. On serological and hormonal evaluation,
      all values are within normal range. He was neurologically intact with motor and
      mental development. An echocardiogram showed calcification of aortic and mitral
      valves. Hypertrophy of internal layer at internal carotid artery suggesting
      atherosclerosis was found by carotid doppler sonography. He is on low dose
      aspirin to prevent thromboembolic episodes and on regular follow up. Gene study
      showed typical G608G (GGC- > GGT) point mutation at exon 11 in LMNA gene. This is
      a rare case of Hutchinson-Gilford progeria syndrome confirmed by genetic analysis
      in Korea.

PMID- 22148006
TI  - Novel ELANE gene mutation in a Korean girl with severe congenital neutropenia.
AB  - Severe congenital neutropenia is a heterozygous group of bone marrow failure
      syndromes that cause lifelong infections. Mutation of the ELANE gene encoding
      human neutrophil elastase is the most common genetic alteration. A Korean female
      pediatric patient was admitted because of recurrent cervical lymphadenitis
      without abscess formation. She had a past history of omphalitis and isolated
      neutropenia at birth. The peripheral blood showed a markedly decreased absolute
      neutrophil count, and the bone marrow findings revealed maturation arrest of
      myeloid precursors at the promyelocyte to myelocyte stage. Her direct DNA
      sequencing analysis demonstrated an ELANE gene mutation (c.607G > C;
      p.Gly203Arg), but her parents were negative for it. She showed only transient
      response after subcutaneous 15 ug/kg/day of granulocyte colony stimulating factor
      administration for six consecutive days. During the follow-up observation period,
      she suffered from subsequent seven febrile illnesses including urinary tract
      infection, septicemia, and cellulitis.

PMID- 22148007
TI  - A clinical study of 35 cases of pincer nails.
AB  - BACKGROUND: Pincer nail is a nail deformity characterized by transverse
      overcurvature of the nail plate. Pincer nail can affect a patient's quality of
      life due to its chronic, recurrent course; however, there have been no clinical
      studies on the pincer nail condition in Korean patients. OBJECTIVE: The purpose
      of this study was to characterize the clinical findings and treatment of pincer
      nail. In addition, possible etiological factors were considered, and treatment
      efficacy was evaluated. METHODS: The medical records and clinical photographs of
      35 patients (12 males, 23 females) who were diagnosed with pincer nail between
      August 1, 2005 and July 31, 2009 were studied. RESULTS: Patient age ranged from
      10 to 77 (52.09+/-17.26) years, and there was a predominance of female (23 out of
      35 patients, F:M=2:1). The mean duration of the disorder was 7.45 years (range
      0.25~40); 85% had pincer nail for at least 1 year. In addition, 40% had a history
      of previous treatment and recurrence. There were 82.8% patients with the common
      type of pincer nails. The most commonly involved nails were both great toenails.
      Among 35 patients, nail grinding was started in 30 patients, and 25 patients
      showed clinical improvement with nail grinding. The width index increased and the
      height index decreased after treatment. The mean follow up period was 8.42 months
      (range 1~27), and 7 patients showed recurrence after 8.8 months (range 2~20).
      Among 35 patients, 5 patients were treated with nail extraction with
      matricectomy, and the symptoms resolved immediately. The mean follow up period
      was 7.6 months (range 0~19), and recurrence was not observed. Onychomycosis was
      also present in 37.1% of patients, and itraconazole pulse therapy for 3 months
      was added. CONCLUSION: The results of this study demonstrate the clinical
      features of pincer nail in Korean patients. The findings show that the common
      type of pincer nail was most common, and nail grinding as a conservative
      treatment greatly improved pincer nails despite a risk of recurrence. When
      onychomycosis was also present, oral antifungal therapy added to nail grinding
      resulted in a more rapid change in nail thickness and clinical improvement.

PMID- 22148008
TI  - Can Platelet-rich Plasma Be Used for Skin Rejuvenation? Evaluation of Effects of
      Platelet-rich Plasma on Human Dermal Fibroblast.
AB  - BACKGROUND: Autologous platelet-rich plasma has attracted attention in various
      medical fields recently, including orthopedic, plastic, and dental surgeries and
      dermatology for its wound healing ability. Further, it has been used clinically
      in mesotherapy for skin rejuvenation. OBJECTIVE: In this study, the effects of
      activated platelet-rich plasma (aPRP) and activated platelet-poor plasma (aPPP)
      have been investigated on the remodelling of the extracellular matrix, a process
      that requires activation of dermal fibroblasts, which is essential for
      rejuvenation of aged skin. METHODS: Platelet-rich plasma (PRP) and platelet-poor
      plasma (PPP) were prepared using a double-spin method and then activated with
      thrombin and calcium chloride. The proliferative effects of aPRP and aPPP were
      measured by [(3)H]thymidine incorporation assay, and their effects on matrix
      protein synthesis were assessed by quantifying levels of procollagen type I
      carboxy-terminal peptide (PIP) by enzyme-linked immunosorbent assay (ELISA). The
      production of collagen and matrix metalloproteinases (MMP) was studied by Western
      blotting and reverse transcriptase-polymerase chain reaction. RESULTS: Platelet
      numbers in PRP increased to 9.4-fold over baseline values. aPRP and aPPP both
      stimulated cell proliferation, with peak proliferation occurring in cells grown
      in 5% aPRP. Levels of PIP were highest in cells grown in the presence of 5% aPRP.
      Additionally, aPRP and aPPP increased the expression of type I collagen, MMP-1
      protein, and mRNA in human dermal fibroblasts. CONCLUSION: aPRP and aPPP promote
      tissue remodelling in aged skin and may be used as adjuvant treatment to lasers
      for skin rejuvenation in cosmetic dermatology.

PMID- 22148009
TI  - Causality assessment of cutaneous adverse drug reactions.
AB  - BACKGROUND: Cutaneous adverse drug reactions (ADRs) are the most common adverse
      reactions attributed to drugs. A systematic and effective approach to a patient
      with suspected drug eruption allows for prompt recognition, classification and
      treatment of cutaneous ADRs. A standardized and effective approach for objective
      causality assessment is necessary to make consistent and accurate identification
      of ADRs. OBJECTIVE: Although the Naranjo algorithm is the most widely used
      assessment tool, it contains many components which are not suitable for clinical
      assessment of ADRs in Korea. The purpose of this study is to compare correlations
      of the Naranjo algorithm and the Korean algorithm to evaluate usefulness of both
      algorithms in order to make a causal link between drugs and cutaneous ADRs. In
      addition, this study classifies the clinical types and causative agents of
      cutaneous ADRs. METHODS: The authors retrospectively reviewed the clinical types
      and laboratory findings of patients who were diagnosed with cutaneous ADRs in the
      dermatology clinic at Gil hospital. One hundred forty-one patients were enrolled
      in this evaluation. The causal relationship of ADRs was assessed by using the
      Naranjo algorithm and Korean algorithm (version 2.0). RESULTS: A cross-tabulation
      analysis was applied to the Naranjo algorithm and Korean algorithm (version 2.0).
      Simple correlation analysis and a Bland-Altman plot were used for statistical
      analysis. Correlation analysis confirmed that the two assessment algorithms were
      significantly correlated. Exanthematous eruptions (68.8%), Stevens- Johnson
      syndrome (10.6%), and urticaria (8.5%) were the most common types of cutaneoues
      ADRs. The most common causative agents were antibiotics/antimicrobials,
      antipyretics/non-steroidal anti-inflammatory drugs, and central nervous system
      depressants. CONCLUSION: The Naranjo algorithm and Korean algorithm (version 2.0)
      were significantly correlated with each other, and thus reliable assessment
      methods to determine cutaneous ADRs.

PMID- 22148010
TI  - Retinoid Induces the Degradation of Corneodesmosomes and Downregulation of
      Corneodesmosomal Cadherins: Implications on the Mechanism of Retinoid-induced
      Desquamation.
AB  - BACKGROUND: Topical retinoids induce skin fragility. As corneodesmosomes are
      important adhesion structures in the epidermal cohesion, an effect of retinoids
      on corneodesmosomes has been suspected. OBJECTIVE: The aim of this study was to
      investigate the effect of retinoid on the expression of corneodesmosomal
      components including desmoglein (DSG) 1, desmocollin (DSC) 1, corneodesmosin
      (CDSN) and kallikrein (KLK)s. METHODS: 2% all-trans-retinol or ethanol was
      applied to the back of hairless mice for five days, and the structure of the
      stratum corneum was examined by transmission electron microscopy. The cultured
      human keratinocytes were treated with all-trans-retinoic acid (RA) in low or high
      calcium media for 24 hours. RESULTS: Topical retinol increased corneocyte
      detachment and degradation of corneodesmosomes. RA significantly decreased DSG1
      and DSC1 expression at the mRNA and protein levels in keratinocytes that were
      cultured in both low- and high-calcium media. On the other hand, CDSN mRNA levels
      did not decrease in low-calcium media or increase in high-calcium media after RA
      treatment. KLK5 and KLK7 expression did not increase after RA treatment.
      CONCLUSION: Our results indicate that DSG1 and DSC1 downregulation by RA could be
      related to the increased degradation of corneodesmosomes and consequent
      desquamation induced by retinoids.

PMID- 22148012
TI  - Hair shaft damage from heat and drying time of hair dryer.
AB  - BACKGROUND: Hair dryers are commonly used and can cause hair damage such as
      roughness, dryness and loss of hair color. It is important to understand the best
      way to dry hair without causing damage. OBJECTIVE: The study assessed changes in
      the ultra-structure, morphology, moisture content, and color of hair after
      repeated shampooing and drying with a hair dryer at a range of temperatures.
      METHODS: A standardized drying time was used to completely dry each hair tress,
      and each tress was treated a total of 30 times. Air flow was set on the hair
      dryer. The tresses were divided into the following five test groups: (a) no
      treatment, (b) drying without using a hair dryer (room temperature, 20C), (c)
      drying with a hair dryer for 60 seconds at a distance of 15 cm (47C), (d) drying
      with a hair dryer for 30 seconds at a distance of 10 cm (61C), (e) drying with a
      hair dryer for 15 seconds at a distance of 5 cm (95C). Scanning and transmission
      electron microscopy (TEM) and lipid TEM were performed. Water content was
      analyzed by a halogen moisture analyzer and hair color was measured with a
      spectrophotometer. RESULTS: Hair surfaces tended to become more damaged as the
      temperature increased. No cortex damage was ever noted, suggesting that the
      surface of hair might play a role as a barrier to prevent cortex damage. Cell
      membrane complex was damaged only in the naturally dried group without hair
      dryer. Moisture content decreased in all treated groups compared to the untreated
      control group. However, the differences in moisture content among the groups were
      not statistically significant. Drying under the ambient and 95C conditions
      appeared to change hair color, especially into lightness, after just 10
      treatments. CONCLUSION: Although using a hair dryer causes more surface damage
      than natural drying, using a hair dryer at a distance of 15 cm with continuous
      motion causes less damage than drying hair naturally.

PMID- 22148011
TI  - Skin characteristics after fractional photothermolysis.
AB  - BACKGROUND: Fractional photothermolysis makes thousands of minute areas called
      microthermal treatment zones on the skin surface and transmits thermal injury to
      facilitate heat shock protein formation around the dermis. Potential side effects
      include acneiform eruption, herpes simplex virus outbreak, erythema, and post
      inflammatory hyperpigmentation. OBJECTIVE: To investigate and compare the changes
      in the skin of Asian patients after two different fractional photothermolysis
      systems (FPS) on a split face. METHODS: A half-split face study was performed
      with 10,600 nm carbon dioxide FPS on the left and 1,550 nm erbium-doped FPS on
      the right side of the face. Only one session of laser irradiation and several
      biophysical measurements were done. RESULTS: Although both FPS proved to be
      effective in treating acne scar and wrinkle patients, a slightly higher
      satisfaction rating was seen with the 10,600 nm FPS treatment. Both types of FPS
      showed a significant increase in transepidermal water loss which decreased
      gradually after treatment and returned to pre-treatment level after 1 week. A
      decreased reviscometer score was sustained for a longer period in wrinkle areas
      treated with 10,600 nm FPS. CONCLUSION: Even though the changes in skin varied
      according to different FPS wave-length, adverse outcomes, such as increased
      erythema and TEWL were entirely subdued within 3 months of treatment.

PMID- 22148013
TI  - Second intention healing after shave excision of benign tumors on the lid margin.
AB  - BACKGROUND: Defects caused by excision of benign lid margin tumors are
      conventionally repaired by reconstructive surgery. However, second intention
      healing is another option for managing wounds on the lid margin. OBJECTIVE: To
      evaluate the effectiveness of second intention healing after a shave excision of
      benign tumors on the lid margin. METHODS: Lid defects following a shave excision
      of the lid margin tumor were allowed to heal by second intention in 25 patients
      (26 lesions). The epithelialzation period was calculated, and cosmetic and
      functional results and complications were evaluated by photographs and
      ophthalmological examination. RESULTS: THE LOCATIONS OF THE DEFECTS WERE AS
      FOLLOWS: upper lid (n=13), lower lid (n=11), and both upper and lower lids (n=1).
      The mean tumor size was 3.8*3.6 mm, and the mean epithelialization period by
      second intention was 6.1+/-1.2 weeks. Pathological examinations revealed
      intradermal nevus (12 cases), compound nevus (five cases), squamous papilloma
      (five cases), and epidermal cyst (three cases). No patients had a corneal
      erosion, trichiasis, or hypertrophic scar, except loss of cilia in two cases. The
      functional and cosmetic results were satisfactory in all patients. CONCLUSION:
      Healing by second intention is a safe and effective alternative to surgical
      reconstruction after a shave excision of benign lid margin tumors.

PMID- 22148014
TI  - IL-31 Serum Protein and Tissue mRNA Levels in Patients with Atopic Dermatitis.
AB  - BACKGROUND: Severe pruritus is the primary symptom in atopic dermatitis (AD).
      Recently, the novel cytokine IL-31 has been implicated in the itching associated
      with AD. OBJECTIVE: We performed this study to determine whether IL-31 serum
      levels are elevated in AD patients and to better characterize the relationship
      between serum IL-31 level and other established laboratory parameters. METHODS:
      We recruited 55 AD patients, 34 with allergic type AD and 21 with non-allergic
      type AD, and 38 healthy, non-atopic controls. We checked the laboratory values,
      severity score, and serum IL-31 levels in all patients and controls, and IL-31
      mRNA levels in lesion skin were measured in 13 subjects with AD and in four
      controls. RESULTS: AD patients displayed significantly higher levels of serum IL
      31 that were associated with serum IgE, disease severity, and subjective itch
      intensity. In AD patients, IL-31 mRNA levels from the lesional skin samples also
      correlated with serum IL-31 level. CONCLUSION: IL-31 is likely one of the many
      mediators inducing inflammation and pruritus in AD. Although our limited sample
      size prevents us from making any definitive conclusions, our data demonstrate a
      strong correlation between IL-31 mRNA level and serum IL-31 protein level, which
      has never been reported before. Moreover, we found correlations between serum IL
      31 level and serum IgE, eosinophil cationic protein, disease severity, and
      subject itch intensity in certain degrees in AD patients.

PMID- 22148015
TI  - Narrowband ultraviolet B phototherapy of early stage mycosis fungoides in korean
      patients.
AB  - BACKGROUND: Narrowband UVB (NBUVB) is currently used to treat early mycosis
      fungoides (MF). There are a number of reports on the efficacy and safety of NBUVB
      in Caucasians, but little data is available for Asians. OBJECTIVE: This study was
      designed to evaluate the effectiveness and safety of NBUVB for early stage MF in
      Korean patients. METHODS: We enrolled 14 patients (12 men, 2 women; age range,
      10~64 years) with clinically and histologically proven MF. Three patients were
      stage IA, and the others were stage IB. The patients received NBUVB phototherapy
      three times a week. The starting dose was 70% of the minimal erythema dose and
      was increased in 20 percent increments if the previous treatment did not cause
      erythema. Clinical response, total number of treatments, total cumulative dose,
      duration of remission and side effects were investigated. RESULTS: Eleven of 14
      patients (78.6%) achieved complete remission within a mean of 15.36+/-5.71 weeks
      (range, 5~27 weeks), 31.0+/-7.4 treatments (range, 16~39 treatments) and a mean
      cumulative UVB dose of 31.31+/-12.16 J/cm(2) (range, 11.4~46.8 J/cm(2)). Three of
      the 14 patients (21.4%) achieved a partial remission. After discontinuation of
      treatment, 6 of 11 patients (54.5%) with complete remission relapsed after a mean
      of 8.5+/-4.09 months. No serious adverse effects were observed except for
      hyperpigmentation (7/14, 50%). CONCLUSION: Our data suggest that NBUVB therapy is
      safe and effective for the treatment of early stage MF in Korean patients.

PMID- 22148016
TI  - Treatment of Striae Distensae with Nonablative Fractional Laser versus Ablative
      CO(2) Fractional Laser: A Randomized Controlled Trial.
AB  - BACKGROUND: Striae distensae are atrophic dermal scars with overlying epidermal
      atrophy causing significant cosmetic concern. Although a variety of laser and
      light sources have been used for the treatment of striae distensae, to date no
      definite 'gold standard' treatment modality has been determined. OBJECTIVE: To
      assess and compare the efficacy and safety of nonablative fractional
      photothermolysis and ablative CO(2) fractional laser resurfacing in the treatment
      of striae distensae. METHODS: Twenty-four ethnic South Korean patients with
      varying degrees of atrophic striae alba in the abdomen were enrolled in a
      randomized blind split study. The patients were treated with 1,550 nm fractional
      Er:Glass laser and ablative fractional CO(2) laser resurfacing. Each half of the
      abdominal lesion was randomly selected and treated three times at intervals of 4
      weeks using the same parameters. Digital photography was conducted and skin
      elasticity and the width of the widest striae in each subject were measured at
      the baseline and 4 weeks after the final treatment. Clinical improvement was
      assessed by comparing pre- and post-treatment clinical photographs by two blinded
      physicians and participant satisfaction rates were evaluated. Skin biopsies were
      taken from three participants. All adverse effects were reported during the
      study. RESULTS: Although they do not statistically differ, both treatments with
      nonablative fractional laser and ablative CO(2) fractional laser showed a
      significant clinical and histopathologic improvement of striae distensae over
      pretreatment sites. CONCLUSION: These results support the use of nonablative
      fractional laser and ablative CO(2) fractional laser as effective and safe
      treatment modalities for striae distensae of Asian skin. However, neither
      treatment showed any greater clinical improvement than the other treatment.

PMID- 22148017
TI  - Milia-like Idiopathic Calcinosis Cutis Occurring in a Toddler Born as a Premature
      Baby.
AB  - Milia-like idiopathic calcinosis cutis (MICC) is characterized by smooth, firm,
      whitish papules resembling milia. Histologically, it appears as a well-defined,
      round, basophilic nodule within the upper dermis. Although the etiology and
      treatment remain unclear, it may resolve spontaneously. Some cases have been
      associated with Down syndrome, and the mean age of MICC patients was 9.9 years
      old. Herein, we report a rare case of MICC that was not associated with Down
      syndrome. Noticeably, the patient, a toddler, was born as a premature baby and
      had an ischemic injury on the right foot at birth. However, the lesions appeared
      on both feet, including the non-injured left foot. Otherwise he was healthy.
      After a 21-month follow-up period, the lesions had almost disappeared without any
      treatment.

PMID- 22148018
TI  - Bowenoid Papulosis of the Vulva and Subsequent Periungual Bowen's Disease Induced
      by the Same Mucosal HPVs.
AB  - We report the case of a 23-year-old woman who developed bowenoid papulosis of the
      vulva and subsequent periungual Bowen's disease. She had a history of a long
      standing periungual wart on her right thumb before the outbreak of periungual
      Bowen's disease. By HPV DNA chip, human papillomavirus (HPV) 11, 18 and 31 were
      identified from the periungual lesions, and HPV 11, 18 and 33 from the vulvar
      lesion. This case supports the theory of anogenital-digital spread of HPV, and
      proposes that the periungual wart may change into Bowen's disease by mucosal
      HPVs. To the best of our knowledge, this case is important as the first Korean
      case of periungual Bowen's disease concurrent with bowenoid papulosis of the
      vulva.

PMID- 22148019
TI  - Wells' syndrome associated with churg-strauss syndrome.
AB  - Churg-Strauss syndrome (CSS) is a multisystem granulomatous vasculitis that is
      characterized by peripheral eosinophilia and the infiltration of eosinophils into
      systemic organs. The skin lesions of CSS consist mainly of palpable purpura and
      nodules. Wells' syndrome (WS) is a rare inflammatory dermatosis that is
      associated with recurrent granulomatous dermatitis and eosinophilia. Since these
      two diseases are rare, any overlap between them is very unusual. Herein, we
      report a patient with CSS, who initially presented a skin eruption of
      erythematous urticarial-plaques, vesicles, and blisters. Upon biopsy, the
      histology of these plaques indicated eosinophilic infiltration and "flame
      figures" within the dermis, which was consistent with a diagnosis of WS. Although
      the association between WS and CSS that was observed in our patient may be purely
      coincidental, it could also suggest a common pathogenetic background of these two
      distinct diseases, as both share several many common features.

PMID- 22148020
TI  - Nicolau syndrome in patient following diclofenac administration: a case report.
AB  - Nicolau syndrome is a rare adverse reaction to a variety of intra-muscular drug
      preparations. The typical presentation is pain around the injection site soon
      after injection, followed by erythema, livedoid patch, hemorrhagic patch, and
      finally, necrosis of skin, subcutaneous fat, and muscle tissue. The phenomenon
      has been related to the administration of a variety of drugs, including non
      steroidal anti-inflammatory drugs, corticosteroids, and penicillin. We report a
      case with typical features associated with diclofenac injection for pain control
      in a patient who had undergone bilateral total knee arthroplasty.

PMID- 22148021
TI  - Treatment of Disseminated Classic Type of Kaposi's Sarcoma with Paclitaxel.
AB  - Classic Kaposi sarcoma (KS) is a rare human herpes virus 8-associated
      angioproliferative disease, and the disseminated classic type of KS in Korea is
      even rarer. The treatment options for classic KS vary and range from surgical
      excision to ionizing irradiation or chemotherapy. Recently, there have been a few
      reports of treating classic KS with paclitaxel, which has been used to treat AIDS
      associated KS and post-transplant KS. We herein report a case of disseminated
      classic type KS in a 78-year-old Korean male patient who showed dramatic response
      after only two cycles of paclitaxel treatment.

PMID- 22148022
TI  - Benign cephalic histiocytosis: a case report.
AB  - Histiocytic skin disorders are usually classified as either Langerhans' cell
      histiocytosis (LCH) or non LCH, based on the pathology. Benign cephalic
      histiocytosis (BCH) is a rare type of non-Langerhans histiocytitic disorder and
      is characterized by self-healing multiple small eruptions of yellow to red-brown
      papules on the face and upper trunk. Histologic features of this disorder show
      dermal proliferation of histiocytes that have intracytoplasmic comma-shaped
      bodies, coated vesicles and desmosome-like structures. In this study, we report
      on a 7-month-old boy who contained small yellow-red papules on his face that
      spread to his upper trunk. The clinical and histologic features in this patient
      were consistent with BCH.

PMID- 22148023
TI  - Kissing nevus of the penis.
AB  - Kissing or divided nevi are similar in shape to congenital melanocytic nevi
      located on an adjacent part of the body that are separated during embryogenesis.
      Kissing nevi of the upper and lower eyelids have been reported infrequently since
      the first report in 1908. Kissing nevi of the penis are very rare, with only 12
      cases being reported until now, and this is the first case report in the Korean
      dermatological literature. A previously healthy 27-year-old man presented with
      asymptomatic black colored patches, which were detected 10 years ago, on the
      glans penis and the prepuce with growth in size. We report here a case of kissing
      nevus of the penis, which showed an obvious mirror-image symmetry relative to the
      coronal sulcus.

PMID- 22148024
TI  - Primary localized cutaneous nodular amyloidosis following local trauma.
AB  - Primary localized cutaneous nodular amyloidosis (nodular amyloidosis) is a rare
      and distinct type of amyloidosis, in which amyloid L deposition is limited to the
      skin and typically manifested as a tumefactive nodule on the acral sites.
      However, the definite cause of nodular amyloidosis is still unknown. Although it
      is relatively well known that the amyloid deposits in nodular amyloidosis
      originate from immunoglobulin light chains secreted by local plasma cells,
      traumatic injury to the skin has rarely been recognized as a triggering factor of
      nodular amyloidosis. Herein, we present a case of a 50-year-old male patient with
      primary localized cutaneous nodular amyloidosis, which occurred after local
      trauma, and discuss the relationship between traumatic damage and dermal amyloid
      L deposition.

PMID- 22148025
TI  - Apocrine Carcinoma of the Groin Possibly Associated with Extramammary Paget's
      Disease.
AB  - Apocrine carcinoma is a rare malignancy with invasive potential. It presents as
      painless, slow-growing, firm or cystic, red nodules with focal ulcerations. The
      tumor is capable of hematogenous dissemination to the liver, lungs, and bone as
      well as lymphatic spread. In addition, apocrine carcinomas cause intra-epidemial
      pagetoid spread. We report a case of an apocrine carcinoma related with extensive
      extramammary Paget's disease (EMPD). The relationship between apocrine carcinoma
      and EMPD remains to be understood. Co-existing cases with apocrine carcinoma and
      EMPD are discussed to better understand the relationship between these two
      malignant apocrine tumors.

PMID- 22148026
TI  - Persistent pemphigus vulgaris showing features of tufted hair folliculitis.
AB  - Pemphigus vulgaris is an autoimmune blistering disease that commonly involves the
      scalp. Lesions of pemphigus vulgaris that persist on the scalp for a long period
      may be accompanied by tufted hair folliculitis. Only two previous accounts of
      tufted hair folliculitis developing in a lesion of pemphigus vulgaris have been
      reported. We report a 51-year-old-man with erosions and clusters of hair on the
      scalp. The scalp lesion had persisted for about 20 years. A histopathological
      examination of the skin lesion on the scalp revealed separation of the epidermis
      and clusters of several adjacent hair follicles. The patient was diagnosed with
      persistent pemphigus vulgaris of the scalp showing features of tufted hair
      folliculitis.

PMID- 22148027
TI  - Black hairy tongue associated with erlotinib treatment in a patient with advanced
      lung cancer.
AB  - Erlotinib is a tyrosine kinase inhibitor that acts on the epidermal growth factor
      receptor (EGFR). There have been many reports of the mucocutaneous side effects
      related to several EGFR inhibitors (EGFRIs). However, no case of black hairy
      tongue (BHT) associated with EGFRI has been reported. Herein, we report the first
      case of erlotinib-induced BHT in a 61-year-old man with advanced lung cancer.
      Considering recent use of EGFRIs worldwide, dermatologists should recognize the
      possible occurrence of BHT associated with EGFRIs such as erlotinib.

PMID- 22148028
TI  - CD20 Positive T Cell Lymphoma Involvement of Skin.
AB  - CD20 positive T cell lymphoma is a rare condition that is associated with the
      coexpressions of CD20 and T cell markers, such as, CD3, CD5, or UCHL-1.
      Positivity for CD20 in this tumor represents an aberrant immunophenotype, but the
      presence of monoclonal T cell receptor (TCR) gene rearrangements and negativity
      for immunoglobulin heavy chain gene rearrangement indicate that this tumor is a T
      cell lymphoma. The majority of cases of CD20 positive T cell lymphoma have been
      reported as immature peripheral T cell lymphoma not otherwise specified. However,
      we believe that this disease is likely to be re-listed as a new disease entity
      after its pathogenesis has been elucidated and more cases have been evaluated.
      Here, we present a case of peripheral T cell lymphoma coexpressing CD20 and T
      cell markers with a demonstrable TCR gene rearrangement, in a patient who had
      been misdiagnosed as having B cell type lymphoma 4 years previously. We
      hypothesize that in this case initially circulating normal CD20+ T cell subsets
      underwent neoplastic transformation and CD20 positive T cell lymphoma
      subsequently developed in the lymph node, and then recurred in the skin due to
      systemic disease or metastasized from the nodal disease.

PMID- 22148029
TI  - Squamous Cell Carcinoma Developing within Lesions of Disseminated Superficial
      Actinic Porokeratosis.
AB  - Disseminated superficial actinic porokeratosis (DSAP) consists of multiple
      annular, hyperkeratotic lesions that have a bilateral distribution on sun-exposed
      areas, particularly the extremities. DSAPs have a wider distribution than
      porokeratosis of Mibelli and usually develop during the 3rd or 4th decade of
      life. Squamous cell carcinoma that arises in the classical type of porokeratosis
      of Mibelli is well-documented, but there are only a few reports of squamous cell
      carcinoma in DSAP. Here, we describe a 62-year-old man with DSAP who developed
      squamous cell carcinoma on his right forearm.

PMID- 22148030
TI  - Congenital and multiple hobnail hemangiomas.
AB  - Hobnail hemangioma (targetoid hemosiderotic hemangioma) is a vascular tumor
      affecting the limbs or trunk. Characteristically, the lesion has a "targetoid"
      clinical feature and dilated vascular spaces lined by hobnail endothelial cells
      at histologic examination. The age of onset is widely variable, form 5~67 years,
      typically occurring in young or middle-aged persons. It is usually apparent as a
      small solitary lesion. However, multiple lesions are identified sometimes.
      Herein, we report two cases of hobnail hemangioma in 7-year-old and 15-year-old
      males. Of note, the former case had a congenital lesion and the latter, multiple
      acquired lesions, which are both rare atypical presentations of the disease.

PMID- 22148031
TI  - Sibutramine (reductil(r))-induced cutaneous leukocytoclastic vasculitis: a case
      report.
AB  - A 24-year old woman presented with hemorrhagic vesicles on her legs. She had
      taken sibutramine (Reductil(r), Abbott Labs., Seoul, South Korea) for 3 months
      and developed skin lesions the week before. A skin biopsy showed leukocytoclastic
      vasculitis with conspicuous eosinophilic infiltration of the tissue. These
      lesions showed improvement after discontinuation of sibutramine. However, 3
      months later the skin lesions recurred on other sites on the lower extremities
      when the patient was rechallenged with the same drug for 2 weeks. Herein, we
      report the first case of necrotizing vasculitis induced by sibutramine.

PMID- 22148032
TI  - Annular plaques on the tongue: what is your diagnosis?
AB  - Geographic tongue is an inflammatory disorder of the tongue characterized by
      asymptomatic erythematous patches with serpiginous borders. Candidiasis of the
      tongue may be confused with geographic tongue. A 63-year-old male patient with
      painful white annular lesions localized to the left side of his tongue is
      presented. He applied topical corticosteroid and antiinflammatory agents, but his
      lesions did not respond to those therapies. Using direct mycologic examination
      and culture, the patient was diagnosed with candidiasis. After systemic and
      topical antifungal therapy, clinical improvement was observed. With this case,
      the clinical forms of oral candidiasis were discussed, and it was suggested that
      the clinical presentation of mucosal candidiasis may vary according to the stage
      of infection and individual immunity.

PMID- 22148033
TI  - Sturge-weber syndrome.
AB  - Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome, characterized by the
      association of facial port-wine hemangiomas in the trigeminal nerve distribution
      area, with vascular malformation(s) of the brain (leptomeningeal angioma) with or
      without glaucoma. Herein, we reported Sturge-Weber syndrome in a 50-year-old man,
      who presented port-wine hemangiomas and epilepsy. In this case, the patient's
      epilepsy episodes from his first year of life had been ignored and separated from
      the entity of SWS by his physicians, which led to delayed treatment. This case
      illustrates the importance of careful examination of patients of any age with
      hemangiomas in the trigeminal nerve with concomitant episodes of epilepsy. In
      such cases, there should be yearly neuroimaging screenings to guaranteed early
      interdisciplinary interventions from the time of definite diagnosis.

PMID- 22148034
TI  - Gianotti-Crosti Syndrome Following Novel Influenza A (H1N1) Vaccination.

PMID- 22148035
TI  - Linear focal elastosis following striae distensae: further evidence of keloidal
      repair process in the pathogenesis of linear focal elastosis.
AB  - Linear focal elastosis (LFE) is a rare dermal elastosis characterized by
      hypertrophic yellowish linear plaques and increased abnormal elastic tissues in
      the lumbosacral area. Although the pathogenesis of this disorder remains unknown,
      it may be associated with keloidal repair process (KRP) of elastic tissues in
      striae distensae (SD), because there have been some reported cases of LFE
      accompanied by SD. We herein report a 14-year-old boy with LFE following SD in
      the lumbar region. Our case supports the hypothesis of KRP in the pathogenesis of
      LFE. Immunohistochemical study for transforming growth factor-beta (TGF-beta) was
      negative. Therefore, we assume that the pathogenesis of KRP in LFE is different
      from that of keloid development, which is the TGF-beta signaling pathway.

PMID- 22148036
TI  - Giant piloleiomyoma of the forehead.
AB  - Cutaneous piloleiomyomas are benign smooth muscle tumors arising from the
      arrector pili muscles. Piloleiomyomas appear as firm dermal papules of skin color
      or with a reddish to brown surface, and are commonly located on the extremities.
      Histologically, these lesions are composed of interlacing bundles of smooth
      muscle cells in the reticular dermis. Our case presented with an unusually large
      nodule on the forehead that was accompanied by intermittent pain. Histological
      analysis was compatible with piloleiomyoma and the lesion showed haphazardly
      arranged bundles of smooth muscle in the dermis. We describe herein an
      interesting case of a giant piloleiomyoma occurring on the forehead.

PMID- 22148037
TI  - Large dermal non neural granular cell tumor on the surgical wound site.
AB  - Granular cell tumors (GCTs) can be divided into neural type with S-100 reactivity
      and non-neural type without that. The latter has not been widely recognized and
      there are only fewer reports available when compared to conventional GCT. A 65
      year-old man was presented with the presence of a painless mass on his back. The
      mass had developed into a small nodule on the scar developed because of previous
      surgery carried out 2 years ago. The tumor consisted of large, polygonal cells
      comprising of an enormous number of faintly eosinophilic small granules in the
      cytoplasm. The cytoplasmic granules were stained positively for periodic acid
      Schiff stain. Immunohistochemical stains for S-100 protein and neuron-specific
      enolase were found to be negative. Herein, we report the appearance of a very
      rare case of non neural GCT developed on the surgical scar in support with
      relevant literature reviews.

PMID- 22148038
TI  - Syringocystadenoma papilliferum of the back combined with a tubular apocrine
      adenoma.
AB  - Syringocystadenoma papilliferum (SCAP) and tubular apocrine adenoma (TAA) are
      rare benign sweat gland tumors. SCAP and TAA may have a histopathologic overlap,
      but few cases of a SCAP combined with a TAA have been reported. Herein we
      describe an unusual case of a SCAP co-existing with a TAA located on the back of
      a 12-year-old girl.

PMID- 22148039
TI  - Primary malignant rhabdoid melanoma.
AB  - Melanoma with rhabdoid features is an uncommon variant of malignant melanoma.
      Here, we describe a rare case of primary rhabdoid malignant melanoma. A 54-year
      old man presented with a black tumor measuring 3*4 cm on the right forearm.
      Histologic sections showed a tumor mass with rhabdoid features composed entirely
      of polygonal neoplastic cells with eccentric nuclei, prominent nucleoli, and
      large hyaline cytoplasmic inclusions. The tumor cells were immunoreactive with
      HMB-45, S100, Fontana-Masson silver and vimentin, and negative for smooth muscle
      actin, CD68, CD34, CD99, synaptophysin, desmin, and PAS. The differential
      diagnosis for this tumor included malignant peripheral nerve sheath tumor,
      malignant peripheral neuroectodermal tumor and rhabdomyosarcoma. The patient was
      treated with a wide excision and a local skin graft. The excised tumor was
      entirely composed of rhabdoid tumor cells. No recurrence or metastasis was
      evident 4 months after removal. This article is relevant to rare cases of primary
      malignant melanomas showing rhabdoid tumor cells over the entire excised lesion.

PMID- 22148040
TI  - Cutaneous extraskeletal osteosarcoma on the scar of a previous bone graft.
AB  - Extraskeletal osteosarcoma (ESOS) is a very rare malignant tumor of mesenchymal
      origin. It is rarer than osseous osteosarcoma and there are very few reports of
      the skin being a primary site. Most reported cutaneous ESOS were accompanied with
      metastasis in other organs. A 56-year-old man presented with a painful, 1.5*0.8
      cm sized, brown-colored nodule on the right girdle area for 3 months. The
      histologic findings revealed a tumor that was confined to the dermis without
      connection to the subcutaneous tissue. In addition, there were large amounts of
      thin and lace-like bony trabeculae and osteoid with neoplastic cells in a highly
      pleomorphic sarcomatous stroma.

PMID- 22148041
TI  - Cutaneous metaplastic synovial cyst of the first metatarsal head area.
AB  - A cutaneous metaplastic synovial cyst (CMSC) is a cyst lined with metaplastic
      synovial tissue, which includes the formation of an intracystic villous structure
      resembling hyperplastic synovial villi. Clinically, the lesion is a tender,
      subcutaneous nodule that usually occurs at the site of previous surgical trauma
      and is frequently misdiagnosed as a suture granuloma. The actual cause remains
      unclear; however, trauma is presumed to be a precipitating factor, as most
      reported cases have demonstrated a history of antecedent cutaneous injury. Here,
      we present a case of CMSC in a 51-year-old woman who presented with a cystic mass
      localized in the left sole. She had no history of previous trauma or surgical
      procedures performed in the area. Although the case explained in this report is a
      spontaneous case of CMSC that occurred without a history of trauma, it is
      believed to have been caused by constant and chronic pressure since CMSC occurred
      in the first metatarsal head area, a part of the sole where heavy pressure is
      consistently applied.

PMID- 22148043
TI  - Syringocystadenoma Papilliferum in Co-existence with Tubular Apocrine Adenoma on
      the Calf.
AB  - Syringocystadenoma papilliferum (SCAP) occurs singly or in association with other
      tumors. Although it is rare, the association of tubular apocrine adenoma (TAA)
      with SCAP in the background of nevus sebaceous (NS) on the scalp is well
      documented. However, the co-existence of these two tumors without background of
      NS has not been reported on the extremities. We report a case of SCAP associated
      with TAA on the calf without pre-existing NS in an adult.

PMID- 22148042
TI  - Castleman's Disease with Cutaneous Involvement Manifestating as Multiple
      Violaceous Plaques on Entire Body.
AB  - Castleman's disease (CD) is an uncommon B-cell lymphoproliferative disorder
      characterized by lymph node hyperplasia with vascular proliferation. Cutaneous
      involvement in CD is rare. A 65-year-old man presented with a 7-year history of
      gradually developing multiple reddish to violaceous indurated plaques on the
      scalp, trunk, and legs. On physical examination, there were palpable enlarged
      cervical, axillary, and inguinal lymph nodes. Laboratory examination revealed
      anemia, thrombocytosis, hyperproteinemia, hypoalbuminemia, and polyclonal
      hypergammaglobulinemia. An inguinal lymph node biopsy and a skin biopsy were
      performed and the patient was diagnosed with the plasma cell type of CD.
      Chemotherapy was started and the lesions have responded to treatment.

PMID- 22148044
TI  - Vulvar skin metastasis of lung squamous cell carcinoma.
AB  - In this study, we examined a case where lung cancer metastasized to the vulvar
      area. A 79-year-old woman that was a heavy smoker was referred to our department
      with a short (two-week) history of dyspnea, and with a painful nodule on her
      right labium majora, which she had noticed almost three years earlier.
      Histopathologically, the specimen appeared as a poorly differentiated squamous
      cell carcinoma. The chest X-ray, chest computerized tomography scan, and
      percutaneous transthoracic needle biopsy via bronchoscopy revealed squamous cell
      carcinoma in the right upper lobe of the lung. Based on these clinical and
      histopathological findings, we concluded that her condition was skin metastasis
      at the right labium majora from the lung cancer, which occurs very rarely.

PMID- 22148045
TI  - Epidermal cysts in a tacrolimus treated renal transplant recipient.
AB  - Tacrolimus, a calcineurin inhibitor, formerly also known as FK506, is a
      macrolactam drug isolated from Streptomyces tsukubaensis. Its mode of action
      closely parallels the action of cyclosprorin A (CsA) and can be used for the
      treatment of inflammatory and autoimmune skin diseases in which systemic CsA has
      proved effective against psoriasis, pyoderma gangrenosum, atopic dermatitis,
      lupus erythematosus and graft versus host disease (GVHD). Although several cases
      of epidermal cysts have been reported in patients using cyclosporine and other
      immunosuppressants after organ transplantation; such types of cases have yet not
      been reported after administration of tacrolimus. However, we report herein a
      case of presence of multiple, various sized epidermal cysts in a renal transplant
      recipient receiving tacrolimus.

PMID- 22148046
TI  - Folliculosebaceous cystic hamartoma in a patient with neurofibromatosis type I.
AB  - Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma composed
      of dilated folliculosebaceous units and mesenchymal elements. It presents as a
      papule or nodule usually on the face and scalp, rarely on the genital or trunk
      area. Histologically, FSCH shares several similar features to sebaceous
      trichofolliculoma. We report one case of FSCH misdiagnosed as a neurofibroma. He
      was a 38-year-old man with a neurofibromatosis type I and a nodule on his left
      earlobe was excised under the impression of neurofibroma. Pathological
      examination revealed FSCH. Although FSCH is clinically not distinctive, awareness
      of the lesion is important to differentiate papulonodular or cyst-like cutaneous
      lesions.

PMID- 22148047
TI  - Genetic study in a case of birt-hogg-dube syndrome.
AB  - Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominantly inherited disorder
      characterized by multiple trichodiscomas, fibrofolliculomas, and acrocordons.
      There is also an increased risk of developing renal neoplasms and lung
      cysts/spontaneous pneumothorax. We present a 43-year-old man with multiple, 2~4
      mm sized, dome-shaped, and skin-colored papules on his cheek and neck. On the
      basis of clinical finding and histopathologic examination on the cheek lesion, it
      was diagnosed as multiple trichodiscomas. Subsequently, molecular analysis
      revealed a mutation in the folliculin gene. We report a rare case of BHDS with a
      proved gene mutation.

PMID- 22148048
TI  - Birt-hogg-dube syndrome, a rare case in Korea confirmed by genetic analysis.
AB  - Simple benign tumors can present as part of a syndrome with substantial
      mortality. Fibrofolliculomas are benign skin tumors most often associated with
      the Birt-Hogg-Dube syndrome (BHDS). The most life-threatening complication of
      this syndrome is renal cancer and other major features include multiple lung
      cysts and spontaneous pneumothorax. We present the case of a 54 year-old man with
      multiple flesh-colored papules on his face confirmed histologically as
      fibrofolliculomas. He had a history of recurrent pneumothorax and chest computed
      tomography showed multiple lung cysts. To confirm the diagnosis of BHDS, we
      conducted gene analysis that revealed a single nucleotide duplication in the
      folliculin (FLCN) gene (Exon 11, C.1285dupC). BHDS confirmed by the FLCN gene
      mutation is rarely reported in Korea. Appropriate investigation is recommended
      whenever a patient with benign skin tumors is encountered.

PMID- 22148049
TI  - Giant vascular eccrine spiradenoma.
AB  - Giant vascular eccrine spiradenomas (GVESs) are a rare variant of the eccrine
      spiradenoma that develops from the sweat gland. It is different from the eccrine
      spiradenoma in its larger size and greater degree of vascularity. Bleeding and/or
      ulceration are common clinical features of this tumor, and are the reason why it
      is often clinically confused with a vascular or malignant tumor. Here, a rare
      case of GVES without bleeding or ulceration is reported.

PMID- 22148050
TI  - Pigmented Basal cell carcinoma of the nipple-areola complex in an elderly woman.
AB  - Basal cell carcinoma (BCC), which frequently occurs in sun-exposed areas of the
      head and neck region, is the most common cutaneous malignancy. The nipple-areola
      complex (NAC) is an uncommon site for BCC to develop. BCCs in this region display
      more aggressive behavior and a greater potential to spread than when found in
      other anatomical sites. This paper outlines the case of 67-year-old female with a
      solitary asymptomatic black plaque on the right areola. The lesion was initially
      recognized as Paget's disease of the nipple by a general surgeon. However, the
      histopathological features showed a tumor mass of basaloid cells, a peripheral
      palisading arrangement and scattered pigment granules. Finally, the patient was
      diagnosed with pigmented BCC of the NAC and was referred to the department of
      dermatology. Positron emission tomography-computed tomography revealed the
      absence of distant metastasis. A wide excision was done. The lesion resolved
      without recurrence or metastasis during 14 months of follow-up.

PMID- 22148051
TI  - Metastatic gastric adenocarcinoma presenting as a solitary plaque on the palm.
AB  - Cutaneous metastases from gastric adenocarcinoma are extremely rare. When
      present, metastasis typically signifies disseminated disease with a poor
      prognosis. We report a case of an 80-year-old male with gastric cancer who
      presented with a single, erythematous plaque on the left palm, a very rare site
      for skin metastasis. Results of a skin biopsy demonstrated that the cutaneous
      metastasis originated from the stomach. This report emphasized the need for
      appropriate investigation into newly appearing, unusual, or persistent skin
      lesions.

PMID- 22148052
TI  - Acral-type Malignant Acanthosis Nigricans Associated with Gastric Adenocarcinoma.
AB  - Acanthosis nigricans is a symmetric eruption characterized by the presence of a
      hyperpigmented, velvety cutaneous thickening, that can develop on any part of the
      body, but characteristically affects the flexural areas of the body. The velvety
      hyperkeratotic lesions can be located on the dorsum of the hands and feet in dark
      skinned people in the form of a variant of acanthosis nigricans called as acral
      acanthotic anomaly or acral type acanthosis nigricans. Although acanthosis
      nigricans is associated with malignant tumors, particularly gastric carcinoma,
      acral type acanthosis nigricans has never been reported to be associated with
      gastric adenocarcinoma. In our present study, we describe a case of 58-year-old
      man with acral type acanthosis nigricans and its association with carcinoma of
      the stomach; a marked improvement was seen in the skin condition of the patient
      with chemotherapy.

PMID- 22148053
TI  - Photodynamic Therapy Combined with CO(2) Laser Vaporization on Disseminated
      Superficial Actinic Porokeratosis: A Report of 2 Cases on the Face.
AB  - Disseminated superficial actinic porokeratosis (DSAP) is a skin condition that
      usually shows a poor response to different modalities of treatment. Herein we
      describe 2 patients with DSAP on the face, each treated with 3 to 4 sessions of
      photodynamic therapy combined with laser vaporization.

PMID- 22148054
TI  - Primary granulocytic sarcoma of the face.
AB  - Myeloid sarcoma is a tumor which consists of myeloblasts or immature myeloid
      cells. This tumor presents in the lymphoid organs, bone, skin, soft tissue,
      various mucosae and organs, and the central nervous system. Granulocytic sarcoma,
      an extramedullary acute myeloid leukemia, is also referred to as chloroma (GS)
      because of its greenish surface color. Granulocytic sarcoma is rare and difficult
      to diagnose. We can easily misdiagnose this tumor as lymphoma or sarcoma,
      especially when there is no evidence of hematologic disorders.
      Immunohistochemical studies are helpful in determining the correct diagnosis.
      Antibodies to myeloperoxidase, lysozyme, and chloroacetate esterase are used for
      the diagnosis of granulocytic sarcoma. In addition, detection of cell surface
      markers such as CD 33, CD 34, CD 68, CD 99, and HLA-DR may be useful. We describe
      a case of GS that presented with bluish nodules on the right cheek of a 54-year
      old woman with immunohistochemical findings for correct diagnosis.

PMID- 22148055
TI  - Late-onset eccrine angiomatous hamartoma associated with a ganglion cyst on the
      sole of the foot.
AB  - Eccrine angiomatous hamartoma (EAH) is a benign, uncommon, combined vascular and
      eccrine malformation. Most cases of this disorder have been single or multiple
      nodules or plaques that appear red, yellow, blue, violaceous, or skin colored.
      EAH may be congenital or appear later in childhood; it rarely arises during
      puberty or adulthood. A 52-year-old female patient visited our department for
      tender subcutaneous cystic tumor on the right sole with a one month history.
      Histopathologic examination confirmed EAH. During excisional biopsy procedure,
      mucinous discharges were observed which were histopathologically diagnosed as
      ganglion.

PMID- 22148056
TI  - Primary Extramammary Paget's Disease Combined with Bowen's Disease in Vulva.
AB  - Extramammary Paget's disease (EMPD) is a uncommon neoplastic condition of
      apocrine gland-bearing skin and its occurrence in combination with Bowen's
      disease is very rare. The most common site of involvement is the vulva, although
      perineal, perianal, scrotal and penile skin may also be affected. EMPD is usually
      not combined with Bowen's disease. We report an interesting case of EMPD combined
      with Bowen's disease, which was confirmed by immunohistochemical stain.

PMID- 22148057
TI  - Acantholytic Anaplastic Extramammary Paget's Disease: A Case Report and Review of
      the Literature.
AB  - Extramammary Paget's disease (EMPD) is an uncommon intraepithelial neoplasm that
      most commonly arises on the vulva and perianal region. Very few cases of EMPD
      revealing a histological Bowenoid appearance have been reported. This study
      describes scrotal EMPD presenting with histological features of Bowen's disease
      in a 79-year-old man. He presented with a 5-year history of a pruritic
      erythematous plaque and a verrucous papule on the scrotum. The verrucous papule
      histopathologically showed Bowenoid features, and the erythematous plaque
      demonstrated acantholytic EMPD. Immunohistochemical findings revealed strong
      expression for carcinoembryonic antigen, Cam 5.2, epithelial membrane antigen,
      cytokeratin (CK) 7, and pancytokeratin (AE1/AE3) in both areas, but negative CK20
      staining, supporting the overall diagnosis of primary acantholytic anaplastic
      EMPD. This is the first reported case of acantholytic anaplastic EMPD in the
      Korean literature.

PMID- 22148058
TI  - Nevus sebaceous accompanying secondary neoplasms and unique histopathologic
      findings.
AB  - Nevus sebaceous (NS) is a type of classical nevus or congenital malformation that
      is often present at birth and commonly involves the scalp or face. The lesion
      usually presents as a linear, yellow, hairless, and verrucous plaque. It has been
      well-established that several benign and malignant tumors can develop from the
      NS; however, there have been no reports about ectopic fat cells in the dermis,
      and cornoid lamella arising from the NS. We report a case of NS on the scalp with
      accompanying unusual histopathologic findings.

PMID- 22148059
TI  - Cutaneous metaplastic synovial cyst of the cheek generated by repetitive minor
      trauma.
AB  - Cutaneous metaplastic synovial cyst (CMSC) refers to a cyst lined by metaplastic
      synovial tissue including villous structures. It is thought to be a tissue
      reaction to local trauma, and most cases have a history of preceding surgery or
      trauma. Clinically, most of the lesion is a tender intradermal nodule that is
      associated with scar tissue. However, dermatologists have difficulty in
      diagnosing CMSC because CMSC is reported only rarely and its clinical
      manifestation can be confused with implantational epidermal cyst, suture
      granuloma or other cutaneous cysts. Thus, a histopathological exam is mandatory
      for diagnosis of CMSC. Herein we report the case of an 18-year-old man who
      developed CMSC on the left cheek on the posterior ramus of the mandible. He had a
      history of repetitive digital manipulation of the lesion before the onset of
      CMSC.

PMID- 22148060
TI  - Deep penetrating benign fibrous histiocytoma of the foot associated with
      throbbing pain.
AB  - Compared to cutaneous benign fibrous histiocytoma (BFH), deep-seated BFH is very
      rare and poorly recognized. Both cutaneous and deep-seated BFH are usually
      asymptomatic. We herein report a 25 year-old woman who presented with a painful
      mass in her foot that was poorly controlled by analgesics and associated with
      walking difficulty. After preoperative ultrasonographic evaluation, the mass was
      completely excised and histologic exam showed spindle cells loosely arranged in
      storiform architecture, with CD34(-), desmin(-), S-100(-), focal CD68(+),
      vimentin(+), smooth muscle actin(+), and factor XIIIa(+). The patient was
      diagnosed with deep-seated BFH based on the histologic, radiologic and
      intraoperative findings.

PMID- 22148061
TI  - Multiple unilateral zosteriform connective tissue nevi on the trunk.
AB  - Connective tissue nevus is not a true tumor, but rather a hamartoma involving
      various components of connective tissue. It presents as a slow-growing, painless,
      flesh-colored, or pink nodule or plaque that is evident from childhood. While any
      region of the body may be affected, there is a predilection for the trunk and
      extremities. A 20-month-old girl presented with three ipsilateral confluent
      popular plaques with zosteriform distribution that had formed over the previous
      17 months on the left chest and abdomen. The patient remained asymptomatic.
      Unlike all previously reported cases demonstrating a single lesion, we report a
      connective tissue nevi in a child who presented with multiple unilateral
      zosteriform lesions, an unusual pattern of distribution without evidence of
      tuberous sclerosis complex.

PMID- 22148062
TI  - A Case of Becker's Nevus with Osteoma Cutis.
AB  - Becker's nevus is a relatively common acquired focal epidermal melanotic
      hypermelanosis usually found in the region of the shoulder girdle of young men.
      Various skeletal malformations and cutaneous dermatoses have been reported in
      Becker's nevus. Osteoma cutis is a rare disorder characterized by compact bone
      formation in the dermis or subcutaneous tissue. Secondary ossification on nevi
      has been reported, but not with Becker's nevus. Herein, we report a case of
      Becker's nevus with accompanying osteoma cutis in an 18-year-old female.

PMID- 22148063
TI  - A case of sinusoidal hemangioma with lipoma.
AB  - Sinusoidal hemangioma is a distinctive subset of a group of lesions known
      collectively as cavernous hemangiomas. Clinically, it develops in adults,
      predominantly females, and presents as a solitary, painless, bluish, deep dermal
      or subcutaneous nodule. Lipoma is the most common benign soft tissue tumor.
      Lipoma is distinguished from sinusoidal hemangioma on both clinical and
      histological grounds. Several studies have suggested that adipocytes originate
      from perivascular cells during adipogenesis. Angiogenic cytokines released by
      adipocytes play a role in the vasoproliferative response. The rearrangement or
      loss of chromosome 13 can also be associated with hemangioma. However, no
      previous cases of sinusoidal hemangioma have been associated with benign tumors
      like lipoma. Here, we describe an unusual case of sinusoidal hemangioma that
      occurred together with a lipoma on the right upper arm of a 43-year-old male.

PMID- 22148064
TI  - Hidradenoma papilliferum occurring on the nasal skin.
AB  - Hidradenoma papilliferum is a rare benign neoplasm that usually occurs in the
      female anogenital area. We present a 43-year-old female with a non-anogenital
      (ectopic) hidradenoma papilliferum on her nose. The patient had had a skin
      colored subcutaneous nodule on her nose for 7 years. The histopathological
      findings showed variously shaped cystic spaces in the tumor. And the lumina were
      surrounded by a single or double layer of cell which showed decapitation
      secretion. In the English dermatological literature, only one case of ectopic
      hidradenoma papilliferum arising in nasal skin has been reported. Hence we
      suggest hidradenoma papilliferum occurring on the nasal skin is a peculiar and
      interesting event.

PMID- 22148065
TI  - Steatocystoma multiplex confined to the scalp with concurrent alopecia.
AB  - Steatocystoma multiplex (SM) is an uncommon disorder of the pilosebaceous unit
      characterized by the development of numerous sebum-containing dermal cysts which
      rarely involves the scalp. Here, we report a case of a 50-year-old man with
      multiple cystic nodules and alopecic patches on his scalp. On histopathological
      examination, the folded cyst was found to be lined by stratified squamous
      epithelium, while flattened sebaceous gland cells were identified in the cystic
      wall. Pigment casts were present in the hair papillae and perifollicular regions,
      suggesting trichotillomania as a possible cause of the observed alopecia. This
      case appears to represent an unusual clinical manifestation of SM.

PMID- 22148066
TI  - A case of auricular ossification.
AB  - Ectopic ossification refers to the process of new bone formation in sites that
      normally do not ossify. The auricle is composed of elastic cartilage, and hence
      is a pliable structure. Auricular ossification is a rare condition that might be
      caused by injurious processes, including frostbite, physical trauma, and
      inflammation as well as processes related to metabolic or endocrine disorders.
      Here, we report a case of unilateral auricular ossification in a 53-year-old
      Korean man who had previously rubbed his ear repeatedly with his hand.

PMID- 22148067
TI  - Cutaneous schwannoma presented as a pedunculated protruding mass.
AB  - Schwannoma is a benign neoplasm of the nerve sheath origin. It arises from the
      nerve sheath of large peripheral or cranial nerves and occurs at the level of the
      subcutaneous fat layer or deeper layer. Cutaneous schwannoma occurs more
      superficially and usually presents as a solitary dermal or subcutaneous nodule.
      We describe a case of cutaneous schwannoma that presented as an erythematous
      pedunculated protruding mass on the left flank of a 19-year-old female. It was
      clinically diagnosed as a granuloma pyogenicum. Shaving biopsy was conducted and
      histological examination revealed an encapsulated tumor mass containing dense,
      spindle-shaped cells whose nuclei are arranged back to back representing Verocay
      body, and a diagnosis of schwannoma was made. This is an unusual case of
      cutaneous schwannoma that presented as a pedunculated protruding mass.

PMID- 22148068
TI  - Pseudocyst of the scalp.
AB  - Pseudocyst of the scalp is described in the Japanese literature as a skin-colored
      cystic tumor localized on the forehead, whereas alopecic and aseptic nodules of
      the scalp are described in the French literature as asymptomatic nodules on the
      scalp that lack a pseudocyst-like architecture. The etiology of these diseases is
      unknown, but the lesions are likely due to follicular occlusion. Here, we report
      a case of pseudocyst of the scalp in a 72-year-old woman. The patient had a dome
      shaped painless tumor on her scalp. Histologic examination showed a pseudocyst
      like architecture with no true cystic wall. Here, we report a case of pseudocyst
      of the scalp and summarize the characteristic features of both pseudocyst of the
      scalp and alopecic and aseptic nodules of the scalp.

PMID- 22148069
TI  - Multiple granulocytic sarcomas in a patient with longstanding complete remission
      of acute myelogenous leukemia.
AB  - Granulocytic sarcoma is an extramedullary tumor composed of granulocytic
      precursor cells. It usually presents as a nodular mass in the course of acute
      myelogenous leukemia. Rarely, the tumor develops in non-hematological conditions
      or in a patient with complete remission from the acute myelogenous leukemia. In
      such cases, aleukemic granulocytic sarcoma can be a preceding sign of systemic
      leukemia or a first sign of hematologic relapse of leukemia. We present an
      unusual case of multiple granulocytic sarcomas developed in a patient with
      longstanding complete remission of acute myelogenous leukemia, who has not had
      bone marrow and peripheral blood involvement for a long time.

PMID- 22148070
TI  - The Appearance of a Candidate Site for a Primary Melanoma: A 5 Year-gap with a
      Melanoma of an Unknown Site.
AB  - Although more than 90% of melanomas have cutaneous origins, melanomas sometimes
      present metastatically with no apparent primary lesion. A 62-year-old female
      presented with black pigmentation on her left thumbnail that had begun 2 years
      earlier and after the biopsy, she was diagnosed with malignant melanoma.
      Interestingly, 7 years earlier, a 4 cm palpable mass on her left axilla had been
      diagnosed as melanoma from an unknown primary site (MUP) with the involvement of
      an axillary lymph node. We speculate that the melanoma of the left thumb was the
      primary site and the melanoma in the axilla was a metastasis from the left thumb,
      and suggest several hypotheses explaining the appearance of the primary lesion as
      acral lentiginous melanoma after detecting a metastatic site. We consider this
      case interesting because it helps us to understand the pathogenesis of MUP and
      reminds physicians to conduct careful periodical work-ups of melanoma patients,
      and highlights the importance of continued long-term follow-up, especially for
      patients with MUP.

PMID- 22148071
TI  - Multiple Facial Papules of Birt-Hogg-Dube Syndrome Treated with a CO(2) Laser.

PMID- 22148073
TI  - Salivary duct carcinoma with striking neutrophil-tumor cell cannibalism.
AB  - Cannibalism of neutrophils by tumor cells has previously been reported in certain
      carcinomas, lymphoma and melanoma. Tumor cannibalism is believed to serve as a
      tumor-immune escape mechanism, associated with high-grade aggressive cancers with
      a significantly increased metastatic potential. This interesting phenomenon has
      not been previously documented in association with salivary gland tumors. We
      report, for the first time, striking neutrophil-tumor cell cannibalism associated
      with a high grade, aggressive and metastatic salivary duct carcinoma of the
      parotid gland highlighted within cytological and surgical excision pathology
      specimens.

PMID- 22148074
TI  - Dissecting thoracic aortic aneurysm presenting with haematemesis.

PMID- 22148072
TI  - Hyperglycemia enhances IGF-I-stimulated Src activation via increasing Nox4
      derived reactive oxygen species in a PKCzeta-dependent manner in vascular smooth
      muscle cells.
AB  - IGF-I-stimulated sarcoma viral oncogene (Src) activation during hyperglycemia is
      required for propagating downstream signaling. The aim of the current study was
      to determine the mechanism by which hyperglycemia enhances IGF-I-stimulated Src
      activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C zeta
      (PKCzeta) in mediating this response in vascular smooth muscle cells (VSMCs).
      Nox4 expression was analyzed in VSMCs exposed to hyperglycemia. The role of Nox4
      derived reactive oxygen species (ROS) in IGF-I-stimulated Src activation was
      investigated via knockdown of Nox4. Different isoforms of PKC were screened to
      investigate their role in hyperglycemia-induced Nox4. The oxidation of Src was
      shown to be a prerequisite for its activation in response to IGF-I during
      hyperglycemia. Hyperglycemia induced Nox4, but not Nox1, and p22 phagocyte
      oxidase (p22phox) expression and IGF-I stimulated Nox4/p22phox complex formation,
      leading to increased ROS generation. Knockdown of Nox4 prevented ROS generation
      and impaired the oxidation and activation of Src in response to IGF-I, whereas
      knockdown of Nox1 had no effect. PKCzeta was shown to mediate the hyperglycemia
      induced increase in Nox4 expression. The key observations in cultured VSMCs were
      confirmed in the diabetic mice. Nox4-derived ROS is responsible for the enhancing
      effect of hyperglycemia on IGF-I-stimulated Src activation, which in turn
      amplifies IGF-I-linked downstream signaling and biological actions.

PMID- 22148075
TI  - Bilateral tension pneumothorax resulting from a bicycle-to-bicycle collision.
AB  - Bilateral tension pneumothorax occurring as a result of recreational activity is
      exceedingly rare. A 10-year-old boy with no previous respiratory symptoms was
      involved in a bicycle-to-bicycle collision during play. He was the only one hurt.
      A few hours later, he was rushed to the general casualty unit of the emergency
      department of our institution with respiratory distress, diminished bilateral
      chest excursions and diminished breath sounds. The correct diagnosis was made
      after a chest radiograph was obtained in the course of resuscitation at the
      casualty unit. Pleural space needle decompression was suggestive of tension only
      on the right. Bilateral tube thoracostomies provided effective relief. He was
      discharged from hospital after a week in excellent health. This case illustrates
      the need for children to have safety instruction to reduce the risks of
      recreational bicycling. Chest radiography may be needed to establish the
      diagnosis of bilateral tension pneumothorax. Needle thoracostomy decompression is
      not always effective.

PMID- 22148076
TI  - A rare cause of hypoglycaemia.
AB  - We describe the case of a 77-year-old man who was admitted with recurrent
      episodes of altered behaviour. These episodes were related to insulin-like growth
      factor II (IGF-II) mediated hypoglycaemia. Imaging revealed a large
      retroperitoneal mass and he underwent debulking surgery uneventfully.
      Histopathology revealed a solitary fibroma with intense immunostaining positive
      for CD34 and vimentin, suggesting a mesenchymal origin of the tumour. Later he
      received chemo/radiotherapy and is on prednisolone with abatement of
      hypoglycaemic episodes.

PMID- 22148077
TI  - Sporadic Creutzfeldt-Jakob disease: early signs and pre-mortem diagnosis.
AB  - A 71-year-old Caucasian woman presented with a 3 week history of progressive
      ataxia followed by rapid cognitive decline. Examination on admission showed
      cerebellar ataxia. This was followed by multifocal dementia with cortical,
      subcortical and brainstem involvements during her hospital stay. Protein 14-3-3
      was identified in the cerebrospinal fluid (CSF) as well as a markedly increased
      S100b. The patient was reviewed by the National CJD Surveillance Unit and the
      National Prion Unit who supported the pre-mortem diagnosis of probable Sporadic
      Creutzfeldt-Jakob disease. The patient deteriorated rapidly, became cortically
      blind, bed bound and died in May 2009, 4 months after the onset of symptoms.

PMID- 22148078
TI  - High-voltage electrical shock without injury.

PMID- 22148079
TI  - A shot in the face.

PMID- 22148080
TI  - Chemical burn to the eyes.

PMID- 22148081
TI  - "Difficult back", turns into "less difficult back" by ultrasonography.

PMID- 22148082
TI  - Morphine and remifentanil-induced cardioprotection: its experimental and clinical
      outcomes.
AB  - During the past few decades, a large number of animal studies demonstrated that
      commonly used opioids could provide cardioprotection against ischemia-reperfusion
      (I/R) injury. Opioid-induced preconditioning or postconditioning mimics ischemic
      preconditioning (I-Pre) or ischemic postconditioning (I-Post). Both delta- and
      kappa-opioid receptors (OPRs) play a crucial role in opioid-induced
      cardioprotection (OIC). Down stream signaling effectors of OIC include ATP
      sensitive potassium (K(ATP)) channels, protein kinase C (PKC), tyrosine kinase,
      phosphatidylinositol-3-kinase (PI3-kinase), extracellular signal regulated
      kinase1/2 (ERK1/2), glycogen synthase kinase-3beta (GSK-3beta), and mitochondrial
      permeability transition pore (MPTP), among others. Recently, various reports also
      suggest that opioids could provide cardioprotection in humans. This review will
      discuss OIC using mostly morphine and remifentanil which are widely used during
      cardiac anesthesia in addition to the clinical implications of OIC.

PMID- 22148083
TI  - Effect of pretreatment with gabapentin on withdrawal movement associated with
      intravenous rocuronium injection.
AB  - BACKGROUND: The major disadvantage of rocuronium is the withdrawal movement
      associated with its injection. The analgesic effect of perioperative gabapentin
      has been evaluated. We investigated the effects of gabapentin on the withdrawal
      movement induced by rocuronium injection. METHODS: 86 ASA physical status I or II
      patients, aged 18-69 years who were scheduled to undergo elective surgery with
      general anesthesia were enrolled. Patients were randomly allocated into two
      groups to receive either gabapentin 600 mg or placebo 2 hours prior to surgery.
      The patient's response to rocuronium injection was graded using a 4-point scale.
      RESULTS: The incidence of withdrawal movement after rocuronium administration was
      significantly lower in the gabapentin group (55.0% in the control group vs 28.6%
      in the gabapentin group). The number of patients with generalized response
      indicating severe pain, was 9 (22.5%) in the control group and 3 (7.1%) in the
      gabapentin group. CONCLUSIONS: Pretreatment with a single oral dose of gabapentin
      600 mg reduced the incidence and severity of withdrawal movement after rocuronium
      administration.

PMID- 22148084
TI  - The effect of the intravenous phenylephrine on the level of spinal anesthesia.
AB  - BACKGROUND: Spinal anesthesia causes hypotension and bradycardia due to
      sympathetic nerve block and it is difficult to predict the level of sensory block
      and the duration of blockade. Recent studies have reported that intravenous
      phenylephrine can reduce the rostral spread of spinal anesthesia in pregnant
      women. We think a phenylephrine infusion will be useful for maintaining the
      baseline blood pressure by reducing the rostral spread of spinal anesthesia
      during the elective surgery of non-obstetric patients. METHODS: SIXTY PATIENTS
      WHO WERE UNDERGOING UROLOGIC SURGERY WERE RANDOMIZED INTO TWO GROUPS: Group C
      (the control group without phenylephrine) and Group P (with the addition of
      phenylephrine). After a bolus infusion of 50 ug phenylephrine following the
      spinal injection, phenylephrine was continuously infused at the rate of 200
      ug/hr. We compared the dermatomal spreads of spinal anesthesia, the hemodynamic
      parameters (blood pressure, heart rate) and the incidences of hypotension between
      the two groups. RESULTS: At 20 minutes, the level of the upper dermatome blocked
      against cold sensation was a median of T8 (interquartile range: T8-T10) for the
      phenylephrine group, as compared with T4 (interquartile range: T4-T6) for the
      control group (P < 0.001). CONCLUSIONS: Intravenous phenylephrine can decrease
      the rostral spread of spinal anesthesia during urologic surgery.

PMID- 22148085
TI  - Predicting the difficulty in performing a neuraxial blockade.
AB  - BACKGROUND: Traumatic placement of a needle during a neuraxial blockade has been
      related to many complications such as postdural puncture headache, trauma to
      neural structures and even spinal hematoma, causing permanent neurologic
      deficits. Although efforts to minimize the complications caused by traumatic
      neuraxial blockade have been made, nothing was found to be clear. The authors
      investigated the predictors of difficult neuraxial blockade using the first
      puncture success and number of attempts as measures to assess the difficulty.
      METHODS: In this prospective observational study, 253 patients scheduled for
      elective surgery underwent spinal or epidural anesthesia. Patient data (age, sex,
      height, weight, body mass index, and quality of anatomical landmarks), the
      provider's level of experience, type of blockade (spinal or epidural), needle
      type/gauge and the distance from skin to subarachnoid or epidural space were
      recorded. Significant variables were first determined by Student's t-test and
      Pearson's chi square test and then logistic and Poisson regression tested the
      association of the first puncture success and number of attempts with the
      significant variables. RESULTS: The provider's level of experience and the
      distance from skin to subarachnoid or epidural space were significant in logistic
      and Poisson regression. Body mass index was significant only in Poisson
      regression and the quality of anatomical landmarks was significant only in
      logistic regression. CONCLUSIONS: Provider's level of experience and the distance
      from skin to subarachnoid or epidural space influenced the difficulty in
      performing a neuraxial blockade.

PMID- 22148086
TI  - Reduction of the incidence of development of venous thromboembolism by ultrasound
      guided femoral nerve block in total knee arthroplasty.
AB  - BACKGROUND: Venous thromboembolism (VTE) and the subsequent development of
      pulmonary embolism (PE) is a major cause of post-operative mortality in total
      knee arthroplasty (TKA). We evaluated whether the addition of an ultrasound
      guided femoral nerve block with general anesthesia affected the incidence in the
      development of VTE following TKA. METHODS: This was a retrospective non
      randomized comparative study with patients assigned to groups based on the
      surgery date (pre-femoral nerve block versus post-femoral nerve block periods).
      All anesthesia and medical records of the patients who had undergone computer
      navigated TKA in our facility between January 2009 and March 2010 were
      retrospectively reviewed. RESULTS: Forty patients were identified; 15 patients
      underwent computer-navigated TKA under general anesthesia alone (Group G) and 25
      patients underwent surgery under general anesthesia combined with ultrasound
      guided femoral nerve block (Group F). The incidence of development of VTE post
      operatively was significantly lower in Group F (P = 0.037). Logistic regression
      analysis identified the use of a femoral nerve block as the most significant
      variable correlating with the incidence of post-operative development of VTE, and
      the odds ratio for VTE development in Group G was 3.12 (95% CI, 0.57-20.56).
      CONCLUSIONS: We suggest the possibility that the addition of a femoral nerve
      block on general anesthesia may reduce the incidence of the development of VTE
      following TKA.

PMID- 22148087
TI  - The effect of nitroglycerin on hemodynamic changes during laparoscopic low
      anterior resection.
AB  - BACKGROUND: More laparoscopic low anterior resections (LAR) are being performed
      in recent years. There has been controversy around the hemodynamic changes
      affected by the Trendelenburg position and pneumoperitoneum during LAR. The goal
      of this study was to analyze the effect of nitroglycerin (NTG) on hemodynamic
      changes during LAR. METHODS: Forty ASA physical status I-II patients undergoing
      LAR were randomized into two groups: the NTG infused group (N group, n = 20) and
      the control group (C group, n = 20). Anesthesia was maintained with sevoflurane
      at 1-3 vol%, air/oxygen (50%/50%) and continuous infusion with remifentanil. The
      N group patients were given 0.5 ug/kg/min of NTG during anesthesia. Mean arterial
      pressure (MAP), heart rate (HR), central venous pressure (CVP), cardiac index
      (CI), stroke volume (SV) and systemic vascular resistance (SVR) were assessed 10
      min after induction (T1), 5 min after pneumoperitoneum in the supine position
      (T2), 10 min after pneumoperitoneum in the Trendelenburg position (T3), 30 min
      after pneumoperitoneum in the Trendelenburg position (T4), 1 hr after
      pneumoperitoneum in the Trendelenburg position (T5) in addition to 5 (T6), 10
      (T7) and 30 min (T8) after removal of the pneumoperitoneum in the supine
      position. RESULTS: The increases of MAP were milder in the N group (22.6-7.3%)
      than the C group (32.3-17.7%) during pneumoperitoneum and while in the
      Trendelenburg position. The significant decreases of HR were maintained in the C
      group, but the changes in HR were not significant in N group during the
      operation. The increases in CVP were less in N group than C group. The increases
      of SVR were milder in N group (19.4-1.4%) than C group (41.7-16.6%) during
      pneumoperitoneum in the Trendelenburg position. CONCLUSIONS: Intraoperative NTG
      infusions were effective to some degree in reducing the hemodynamic changes
      during pneumoperitoneum with Trendelenburg positioning for LAR.

PMID- 22148088
TI  - A comparison of the influence of 2.7% sorbitol-0.54% mannitol and 5% glucose
      irrigating fluids on plasma serum physiology during hysteroscopic procedures.
AB  - BACKGROUND: 2.7% sorbitol-0.54% mannitol has been selected as an alternative
      irrigating fluid during endoscopic surgery for its theoretical advantages. We
      compared the influence of 2.7% sorbitol-0.54% mannitol (UrosolTM, CJ Pharma,
      Seoul, Korea) and 5% glucose as an irrigating solution for hysteroscopic
      myomectomy & polypectomy in the occurrence of associated complications. METHODS:
      Thirty patients scheduled for a hysteroscopic operation were included in a
      prospective randomized trial comparing 2.7% sorbitol-0.54% mannitol solution
      (Group S, n = 15) and 5% glucose (Group G, n = 15) as an irrigating fluid. We
      recorded the amount of the irrigating fluids, the amount of fluid intake, and the
      duration of the procedure. Serum sodium, chloride, potassium, glucose values, and
      serum osmolality were measured before (just after the induction, T1), during
      (when 2 L of irrigation fluid was infused, T2), and after (1 h after the end of
      the operation, T3) the hysteroscopic procedure. RESULTS: The mean volume of
      absorbed irrigating fluid was 185.0 +/- 73.5 ml in Group G and 175.4 +/- 50.5 ml
      in Group S. Transient hyperglycemia occurred in one patient of Group G. No
      differences were found in the intraoperative and postoperative levels of serum
      sodium, potassium, chloride, glucose and osmolality in both groups. CONCLUSIONS:
      There was no clinical evidence of hyponatremic hypoosmolality in any of the
      patients. We found no difference between 2.7% sorbitol-0.54% mannitol and 5%
      glucose as an irrigating fluid for hysteroscopic procedures with mild to moderate
      irrigant absorption.

PMID- 22148089
TI  - Postoperative nausea and vomiting after mastoidectomy with tympanoplasty: a
      comparison between TIVA with propofol-remifentanil and balanced anesthesia with
      sevoflurane-remifentanil.
AB  - BACKGROUND: There is growing interest in the anesthetic approach using total
      intravenous anesthesia (TIVA) with propofol and remifentanil for the prevention
      of postoperative nausea and vomiting (PONV). The aim of this study was to compare
      between the two anesthetic techniques for preventing PONV in the patients
      undergoing mastoidectomy with tympanoplasty. METHODS: After obtaining informed
      consent, 62 patients aged between 20 to 60 years undergoing elective
      mastoidectomy and tympanoplasty were randomized into two equal study groups:
      group P/R (n = 31) included patients undergoing TIVA with propofol and
      remifentanil, and group S/R (n = 31) included patients undergoing balanced
      anesthesia with sevoflurane and remifentanil. The incidences of PONV and complete
      response (no PONV, no rescue) were assessed at 1 and 24 h after surgery, using
      the Rhodes Index. Also, the usage of rescue antiemetics and pain intensity were
      recorded. RESULTS: The Rhodes Index including the occurrence score, distress
      score and experience score was significantly lower in the P/R group compared to
      that in the S/R group during the study period (P < 0.05), and the incidence of
      complete response was significantly higher in the P/R group compared to that in
      the S/R group, during the first 24 h after surgery. 4 patients in the S/R group
      requested antiemetics during the first 1 h after surgery. There were no
      significant differences in pain intensity among groups. CONCLUSIONS: Compared to
      balanced anesthesia with sevoflurane and remifentanil, TIVA with propofol and
      remifentanil was followed by significantly lower incidence and severity of PONV.

PMID- 22148090
TI  - Ramosetron for the prevention of postoperative nausea and vomiting (PONV): a meta
      analysis.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) remains a challenge for
      patients and health professionals despite various newly developed prophylactic
      interventions. We reviewed the efficacy and safety of ramosetron in randomized
      controlled trials (RCTs) for the prevention of PONV. METHODS: We reviewed 18
      randomized controlled trials investigating the efficacy and safety of ramosetron
      in comparison with placebo or any other drugs. Relevant studies were searched in
      the MEDLINE, SCOPUS, and the Cochrane database libraries. Our end points of
      concern were prevention of PONV and adverse effects as dichotomous data. RESULTS:
      The prophylactic effect of 0.3 mg ramosetron was observed in early PON (relative
      risk, RR: 0.4; 95% CI 0.3-0.6), early POV (RR: 0.3; 95% CI 0.1-0.6), late POV
      (RR: 0.3; 95% CI 0.1-0.6), but not late PON (RR: 0.7; 95% CI 0.5-1.0). Compared
      with placebo, the efficacy of 0.3 mg ramosetron in adults and 6 ug/kg in children
      were consistently beneficial in preventing PONV overall (RR: 0.4; 95% CI: 03
      0.6). The effects of 0.3 mg ramosetron and 3 mg granisetron were similar. No
      serious side effects or adverse events resulted from ramosetron and other active
      drugs, and incidence was similar to those of the placebo group. CONCLUSIONS:
      Ramosetron is effective and safe in children and adults without serious adverse
      effects compared with placebo or other active drugs, as shown in pooled data of
      RCTs, in terms of the prevention of PONV.

PMID- 22148091
TI  - Preemptive analgesic efficacy of ultrasound-guided transversus abdominis plane
      block in patients undergoing gynecologic surgery via a transverse lower abdominal
      skin incision.
AB  - BACKGROUND: The transversus abdominis plane block is recently described
      peripheral block to providing analgesia to the anterior abdominal wall. The goal
      of this study is to evaluate the analgesic efficacy of the ultrasound-guided
      transversus abdominis plane block (US-TAP block) in patients undergoing
      gynecologic surgery via a transverse lower abdominal skin incision. METHODS:
      Thirty-two patients undergoing gynecologic surgery were randomized to undergo
      standard care such as PCA, or to receive additional US-TAP block with standard
      care. After general anesthesia induction, a bilateral US-TAP block was performed
      using 0.375% ropivacaine 20 ml on each side. Postoperative demand of rescue
      analgesics in PACU and ward were recorded. Each patient was assessed
      postoperatively by a blinded investigator in the postanesthesia care unit (PACU)
      and at 2, 6, 10, 24, 48 hr postoperatively to investigate pain, drowsiness,
      nausea and itch. RESULTS: The US-TAP block reduced pain intensity compared to
      standard care in the PACU (5.2 +/- 3.1 vs 8.4 +/- 1.3) and at 2, 24 postoperative
      hours (3.0 +/- 2.4 vs 5.2 +/- 2.4, 0.9 +/- 1.5 vs 2.2 +/- 1.9). Fentanyl
      requirements in PACU was reduced (20.3 +/- 20.9 vs 62.5 +/- 35.4 ug, P < 0.05).
      In ward, pethidine requirements was reduced (21.9 +/- 28.7 vs 56.3 +/- 34.8 mg, P
      < 0.05). CONCLUSIONS: The US-TAP block with standard care provide more effective
      analgesia after gynecologic surgery via a transverse lower abdominal skin
      incision.

PMID- 22148092
TI  - Gender difference and change of alpha(1)-adrenoceptors in the distal mesenteric
      arteries of streptozotocin-induced diabetic rats.
AB  - BACKGROUND: The purpose of this study was to evaluate the gender-related changes
      in the function and distribution of alpha(1)-adrenoceptors in the distal
      mesenteric artery of streptozotocin (STZ)-induced diabetic rats at the level of
      alpha(1)-adrenoceptor subtypes. METHODS: Diabetes was induced by intravenous
      injection of STZ in a dose of 60 mg/kg through the tail vein in 8 week-old male
      or female Sprague-Dawley rats (n = 13/group). Age-matched normal rats (n = 15)
      were used as a control group. Four weeks after STZ injection, the change in mean
      arterial pressure caused by a 45 degrees  tilting was recorded. The alpha(1)
      adrenoceptor subtypes mediating contractions of the distal mesenteric artery were
      investigated using the agonist, phenylephrine as well as subtype-selective
      antagonists including prazocin, 5-methylurapidil, and BMY 7378. The expression of
      alpha(1)-adrenoceptor subtypes of each artery was examined by immunofluorescence
      staining and western blotting using subtype selective antibodies. RESULTS:
      Compared with normal male rats, the contractile response to phenylephrine was
      decreased in the distal mesenteric artery in normal female rats. Moreover, a
      decrease in contractile force was observed in STZ-induced diabetic rats compared
      with age-matched controls. Western blotting revealed that there was the
      difference between normal male and female rats in manifestation of the alpha(1D)
      adrenoceptor. In STZ-induced male and female diabetic rats, all alpha(1)
      adrenoceptor subtypes were decreased in distal mesenteric arteries, compared with
      normal rats. CONCLUSIONS: There was the gender-related functional difference of
      alpha(1)-adrenoceptors in normal rats. In both male and female rats, diabetes
      decreased the contractile response in mesenteric arteries, which might be caused
      by the overall change in alpha(1)-adrenoceptor.

PMID- 22148093
TI  - Anesthetic management of an adult patient with Rett syndrome and limited mouth
      opening -A case report-.
AB  - Rett syndrome is a neurological disease that occurs only in females and it
      manifests with mental retardation, seizures, movement disorders, autistic
      behavior and abnormal breathing. A 19-year-old female with Rett syndrome
      underwent ophthalmologic surgery under general anesthesia at our institution.
      Airway control was difficult due to her limited mouth opening. We recommend that
      anesthesiologists should have proper knowledge about this disease and the
      patients to avoid the complications and problems that can be encountered during
      the perioperative period.

PMID- 22148094
TI  - The prophylactic use of recombinant factor VIIa in a patient with DeBakey type
      III aortic dissection -A case report-.
AB  - Little is known about the prophylactic use of recombinant factor VIIa (rFVIIa) in
      patients undergoing surgery for a bleeding aorta employing cardiopulmonary
      bypass. We report the successful use of rFVIIa in a patient undergoing
      hypothermic circulatory arrest and prolonged cardiopulmonary bypass for repair of
      a DeBakey type III aortic dissection.

PMID- 22148095
TI  - Hypotension in patients administered indigo carmine containing impurities -A case
      report-.
AB  - Indigo carmine has been used for eight decades with few adverse effects. Several
      of our patients, however, experienced severe hypotensive episodes after indigo
      carmine administration within a period of one month. Analysis of the raw
      materials used to formulate the preparation of indigo carmine we used showed that
      they contained impurities. Following recall of these impure materials, none of
      our patients experienced further hypotensive episodes.

PMID- 22148096
TI  - Intraoperative hypertension in a patient with undiagnosed pheochromocytoma under
      spinal anesthesia.

PMID- 22148097
TI  - Anesthetic experience in a pediatric patient with mastocytosis.

PMID- 22148098
TI  - High-dose aspirin is required to influence plasma fibrin network structure in
      patients with type 1 diabetes.
AB  - OBJECTIVE: Patients with type 1 diabetes form a less permeable fibrin network,
      which could contribute to their increased risk of cardiovascular disease (CVD).
      Low-dose aspirin treatment is the standard in the management of CVD; however, the
      effect seems reduced in patients with diabetes. We investigated the effects of
      low- and high-dose aspirin treatment on fibrin network formation in patients with
      type 1 diabetes (primary aim) and the possible interaction between the treatment
      effects of aspirin on fibrin network permeability and glycemic control in these
      patients (secondary aim). RESEARCH DESIGN AND METHODS: Forty-eight patients (24
      subjects with good [HbA(1c) <7.4%] and 24 subjects with poor [HbA(1c) >8.4%]
      glycemic control) were randomly assigned to treatment with 75 or 320 mg/day
      aspirin during 4 weeks in a crossover fashion. A 4-week washout period separated
      the treatment periods. The plasma fibrin network was assessed by determination of
      the permeability coefficient (K(s)). RESULTS: Treatment with 75 mg aspirin did
      not influence fibrin network permeability (K(s)). However, K(s) increased
      significantly during treatment with 320 mg aspirin (P = 0.004), and a significant
      treatment effect was seen compared with treatment with 75 mg aspirin (P = 0.009).
      The increase in K(s) during high-dose aspirin treatment was significant in
      patients with poor glycemic control (P = 0.02), whereas K(s) only tended to
      increase in patients with good glycemic control (P = 0.06). CONCLUSIONS: A high
      dose of aspirin is required to influence fibrin network permeability in patients
      with type 1 diabetes. The observed lack of effect with low-dose aspirin may
      contribute to aspirin treatment failure in diabetes.

PMID- 22148100
TI  - The important roles of interstitial cells of cajal and cholinergic receptors on
      diabetes related dysfunction of colon.

PMID- 22148099
TI  - Total and high-molecular-weight adiponectin and risk of incident diabetes in
      older people.
AB  - OBJECTIVE: To delineate the associations of total adiponectin, high-molecular
      weight (HMW) adiponectin, and the HMW-to-total adiponectin ratio with diabetes in
      older adults. RESEARCH DESIGN AND METHODS: Total and HMW adiponectin were
      measured in a population-based study of older adults. The relations of total
      adiponectin, HMW adiponectin, and their ratio with incident diabetes (n = 309)
      were assessed in 3,802 individuals. RESULTS: Total and HMW adiponectin were
      highly correlated (r = 0.94). Analysis using cubic splines revealed that the
      associations between total and HMW adiponectin and new-onset diabetes were not
      linear. Specifically, after adjustment for confounders, there were similar
      inverse relationships for total (hazard ratio per SD 0.49 [95% CI 0.39-0.63]) and
      HMW adiponectin (0.42 [0.32-0.56]) with diabetes up to values of 20 and 10 mg/L,
      respectively, above which the associations plateaued. These associations
      persisted after adjustment for potential mediators (blood pressure, lipids, C
      reactive protein, and homeostasis model assessment of insulin resistance [HOMA
      IR]). There was, however, evidence of interaction by HOMA-IR in the lower range
      of adiponectin, with stronger inverse associations among insulin-sensitive than
      insulin-resistant participants. HMW-to-total adiponectin ratio showed a linear
      adjusted association with outcome, but this was abolished by inclusion of
      mediating variables. CONCLUSIONS: In this older cohort, increasing concentrations
      of total and HMW adiponectin were associated with comparably lower risks of
      diabetes, but these associations leveled off with further increases above
      concentrations of 20 and 10 mg/L, respectively. The more pronounced risk
      decreases at the lower range among participants without insulin resistance
      support a role for adiponectin that is independent of baseline hyperinsulinemia,
      but this will require further investigation.

PMID- 22148101
TI  - Patient or physician - who is able to evaluate gastroesophageal reflux disease
      symptoms better?

PMID- 22148102
TI  - Vagal control of satiety and hormonal regulation of appetite.
AB  - The paradigm for the control of feeding behavior has changed significantly. In
      this review, we present evidence that the separation of function in which
      cholecystokinin (CCK) controls short-term food intake and leptin regulate long
      term eating behavior and body weight become less clear. In addition to the
      hypothalamus, the vagus nerve is critically involved in the control of feeding by
      transmitting signals arising from the upper gut to the nucleus of the solitary
      tract. Among the peripheral mediators, CCK is the key peptide involved in
      generating the satiety signal via the vagus. Leptin receptors have also been
      identified in the vagus nerve. Studies in the rodents clearly indicate that
      leptin and CCK interact synergistically to induce short-term inhibition of food
      intake and long-term reduction of body weight. The synergistic interaction
      between vagal CCK-A receptor and leptin is mediated by the phosphorylation of
      signal transducer and activator of transcription3 (STAT3), which in turn,
      activates closure of K(+) channels, leading to membrane depolarization and
      neuronal firing. This involves the interaction between CCK/SRC/phosphoinositide 3
      kinase cascades and leptin/Janus kinase-2/phosphoinositide 3-kinase/STAT3
      signaling pathways. It is conceivable that malfunctioning of these signaling
      molecules may result in eating disorders.

PMID- 22148104
TI  - Overlap syndrome of functional dyspepsia and irritable bowel syndrome - are both
      diseases mutually exclusive?
AB  - Among functional gastrointestinal (GI) disorders, functional dyspepsia (FD) and
      irritable bowel syndrome (IBS) are important to public health around the world
      and are frequently encountered in general practice. Upper GI symptoms such as
      heartburn, postprandial fullness, early satiety, epigastric pain or burning and
      lower GI symptoms such as constipation and diarrhea often coexist. Although the
      prevalence of FD-IBS overlap would be influenced by the selection of the study
      population, the overlap rate of FD-IBS could be in the range of 11%-27%.
      Specifically, FD-IBS overlap is associated with more severe symptoms than FD
      alone or IBS alone. Since clinical overlap, especially FD-IBS overlap, is very
      common, the 2 syndromes should not be treated in a mutually exclusive fashion.

PMID- 22148103
TI  - The immune system in irritable bowel syndrome.
AB  - The potential relevance of systemic and gastrointestinal immune activation in the
      pathophysiology and symptom generation in the irritable bowel syndrome (IBS) is
      supported by a number of observations. Infectious gastroenteritis is the
      strongest risk factor for the development of IBS and increased rates of IBS-like
      symptoms have been detected in patients with inflammatory bowel disease in
      remission or in celiac disease patients on a gluten free diet. The number of T
      cells and mast cells in the small and large intestine of patients with IBS is
      increased in a large proportion of patients with IBS over healthy controls.
      Mediators released by immune cells and likely from other non-immune competent
      cells impact on the function of enteric and sensory afferent nerves as well as on
      epithelial tight junctions controlling mucosal barrier of recipient animals,
      isolated human gut tissues or cell culture systems. Antibodies against microbiota
      antigens (bacterial flagellin), and increased levels of cytokines have been
      detected systemically in the peripheral blood advocating the existence of
      abnormal host-microbial interactions and systemic immune responses. Nonetheless,
      there is wide overlap of data obtained in healthy controls; in addition, the
      subsets of patients showing immune activation have yet to be clearly identified.
      Gender, age, geographic differences, genetic predisposition, diet and differences
      in the intestinal microbiota likely play a role and further research has to be
      done to clarify their relevance as potential mechanisms in the described immune
      system dysregulation. Immune activation has stimulated interest for the potential
      identification of biomarkers useful for clinical and research purposes and the
      development of novel therapeutic approaches.

PMID- 22148105
TI  - Should we still subcategorize helicobacter pylori-associated dyspepsia as
      functional disease?
AB  - Functional dyspepsia is a group of disorders featuring symptoms believed to be
      derived from the stomach and duodenum such as upper abdominal discomfort, pain,
      postprandial fullness and early satiety. A key diagnostic requisite is the
      absence of organic, metabolic, or systemic disorders to explain "dyspeptic
      symptoms." Therefore, when peptic ulcer diseases (including scars), erosive
      esophagitis and upper gastrointestinal malignancies are found at endoscopic
      examinations, the diagnosis of functional dyspepsia is excluded. One notable
      exception, however, is Helicobacter pylori infection. According to the Rome III
      definition, H. pylori infection is included in functional dyspepsia. This is an
      obvious deviation from the diagnostic principle of functional dyspepsia, since H.
      pylori infection is a definite cause of mucosal inflammation, which affects a
      number of important gastric physiologies such as acid secretion, gastric
      endocrine function and motility. The chronic persistent nature of infection also
      results in more dramatic mucosal changes such as atrophy or intestinal
      metaplasia, the presence of which in the esophagus (Barrett's esophagus)
      precludes the diagnosis of functional dyspepsia. Since careful endoscopic
      examination can diagnose reliably H. pylori infection not only in Japan but also
      in Western contries, it is now feasible and more logical to exclude patients with
      chronic gastritis caused by H. pylori infection as having dyspeptic symptoms. It
      is time to establish the Asian consensus to declare that H. pylori infection
      should be separated from functional dyspepsia.

PMID- 22148106
TI  - Alterations of colonic contractility in long-term diabetic rat model.
AB  - BACKGROUND/AIMS: Dysfunction of the gastrointestinal tract occurs in about 76% of
      patients who are diabetic for more than 10 years. Although diabetes-related
      dysfunctions of the stomach such as gastroparesis have been extensively studied
      over the recent years, studies about the mechanism underlying colonic symptoms in
      long-term diabetes models are rare. Therefore, the goal of our study was to
      clarify the nature of colonic dysfunction in a long-term diabetic rat model.
      METHODS: The characteristics of colonic smooth muscle were investigated in Otsuka
      Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes.
      These results were compared to those obtained from Long-Evans Tokushima Otsuka
      (LETO) control rats. RESULTS: Spontaneous contractility of the proximal colon was
      significantly decreased in the diabetic rats compared to the controls, while the
      spontaneous contractility of the distal colon was not. The number of interstitial
      cells of Cajal networks in the proximal colon was greatly decreased in diabetic
      rats compared to the controls. Contractility of the proximal colon in response to
      carbachol, an acetylcholine receptor agonist, was significantly weaker in the
      diabetic rats. In addition, the degree of relaxation in response to nitric oxide
      in the proximal colon of diabetic rats also appeared to be attenuated.
      CONCLUSIONS: The results from our study suggest that the decrease of interstitial
      cells of Cajal network, cholinergic receptors, and neuronal nitric oxide synthase
      in the proximal colon plays important roles in diabetes-related dysfunction of
      colon.

PMID- 22148107
TI  - Physicians and patients measure different dimension on assessment for
      gastroesophageal reflux disease-related symptoms [corrected].
AB  - BACKGROUND/AIMS: Gastroesophageal reflux disease is a highly prevalent disease.
      Assessing treatment efficacy is critical in that clinical endpoints are properly
      evaluated. Clinical tools for symptoms severity assessment should be
      discriminative, predictive and evaluative. METHODS: In this study we compared a
      patient-oriented symptoms evaluation (ReQuestTM) vs a structured interview
      assessment initiated by a physician (sickness impact profile [SIP]). Both
      questionnaires were analyzed in a multidimensional space using latent factors.
      Five dimensions were found: 1 for the short ReQuestTM questionnaire and 4 for
      SIP. RESULTS: We included 1,522 women and 1,296 men; mean age was 36 +/- 7 years,
      and mean body mass index was 26 +/- 4. The score questionnaire assessment
      evaluation by physicians and patients did not correlate between them (between r =
      0.03 and 0.26) except nausea and sleep disorder (r = 0.45 and 0.51) but both were
      sensitive enough to detect changes after treatment (P < 0.05). Medical specialty
      of the physician showed effect on the score of both, ReQuestTM and SIP
      evaluation. Questionnaire variance decomposition due to specialist was only 2% (P
      < 0.05). CONCLUSIONS: While both evaluations are orthogonal (non-correlated),
      meaning patients and physicians measured diverse aspects of the same disease,
      they both were able to measure patient's improvement with treatment.

PMID- 22148108
TI  - Comparison of clinical characteristics of patients with gastroesophageal reflux
      disease who failed proton pump inhibitor therapy versus those who fully
      responded.
AB  - BACKGROUND/AIMS: Refractory gastroesophageal reflux disease (GERD) is very
      common, affecting up to 40% of the patients receiving proton pump inhibitor (PPI)
      therapy. However, there is not much information about the clinical
      characteristics of these patients. The aim of the study is to compare the
      clinical characteristics of PPI responders vs non-responders. METHODS:
      Consecutive GERD patients receiving PPI once or twice daily were evaluated by a
      questionnaire and a personal interview regarding their demographics, habits,
      clinical characteristics and endoscopic findings. The patients were divided into
      3 groups: Patients who fully responded to PPI once daily (Group A, n = 111),
      patients who failed PPI once daily (Group B, n = 78) and patients who failed PPI
      twice daily (Group C, n = 56). RESULTS: A total of 245 patients (59.3% females,
      52 +/- 17.2 years of age) were included in this study. Cross-group differences (A
      vs B vs C) were detected for hiatal hernia (33% vs 51% vs 52%, P = 0.011);
      erosive esophagitis (19% vs 51% vs 30%, P < 0.0001); cough (24% vs 44% vs 43%, P
      = 0.007); sleep disturbances (19% vs 30% vs 38%, P = 0.033); chest symptoms (21%
      vs 35% vs 41%, P = 0.010); Helicobacter pylori status (25% vs 33% vs 48%, P <
      0.0001), disease duration (1.6 +/- 0.8 vs 1.9 +/- 1.0 vs 2.0 +/- 1.1 years, P =
      0.007), performed lifestyle interventions (68.5% vs 46.7% vs 69.6%, P = 0.043)
      and compliance (84% vs 55% vs 46%, P < 0.0001). CONCLUSIONS: PPI failure (either
      once or twice daily) appears to be significantly associated with atypical GERD
      symptoms, disease duration and severity, H. pylori status, obesity, performed
      lifestyle interventions and compliance as compared with PPI responders.

PMID- 22148109
TI  - Mosapride accelerates the delayed gastric emptying of high-viscosity liquids: a
      crossover study using continuous real-time C breath test (BreathID System).
AB  - BACKGROUND/AIMS: The administration of liquid nutrients to patients is often
      accompanied by complications such as gastroesophageal reflux. To prevent
      gastroesophageal reflux, high-viscosity liquid meals are used widely, however, it
      still remains controversial whether high-viscosity liquid meals have any effect
      on the rate of gastric emptying. The present study was conducted with the aim of
      determining whether high-viscosity liquid meals had any effect on the rate of
      gastric emptying and mosapride might accelerate the rate of gastric emptying of
      high-viscosity liquid meals. METHODS: Six healthy male volunteers underwent 3
      tests at intervals of > 1 week. After fasting for > 8 hours, each subject
      received one of three test meals (liquid meal only, high-viscosity liquid meal
      [liquid meal plus pectin] only, or high-viscosity liquid meal 30 minutes after
      intake of mosapride). A (13)C-acetic acid breath test was performed, which
      monitored the rate of gastric emptying for 4 hours. Using the Oridion Research
      Software (beta version), breath test parameters were calculated. The study
      parameters were examined for all the 3 test conditions and compared using the
      Freidman test. RESULTS: Gastric emptying was significantly delayed following
      intake of a high-viscosity liquid meal alone as compared with a liquid meal
      alone; however, intake of mosapride prior to a high-viscosity liquid meal was
      associated with a significantly accelerated rate of gastric emptying as compared
      with a high-viscosity liquid meal alone. CONCLUSIONS: This study showed that high
      viscosity liquid meals delayed gastric emptying: however, mosapride recovered the
      delayed rate of gastric emptying by high-viscosity liquid meals.

PMID- 22148110
TI  - The evaluation of otilonium bromide treatment in asian patients with irritable
      bowel syndrome.
AB  - BACKGROUND/AIMS: Antispasmodics including otilonium bromide (OB) are recommended
      to treat irritable bowel syndrome (IBS). However, reports about OB experience in
      Asia is sparse. The purpose of present study was to provide the efficacy of OB in
      treating Asian IBS patients. METHODS: Overall, 117 IBS patients meeting Rome II
      criteria were enrolled in an 8-week, double-blind, active-controlled and single
      center trial. Randomized participants received either OB 40 mg or mebeverine 100
      mg 3 doses daily. The primary endpoints were to evaluate the net changes of
      abdominal pain/discomfort frequency score (APDFS) and safety profile, while the
      secondary endpoints were to assess the changes in abdominal pain/discomfort
      intensity, flatulence, abdominal bloating, satisfied stool frequency etc.
      RESULTS: Finally, 49 OB and 52 mebeverine subjects were eligible for efficacy
      analysis. Compared to baselines in per protocol populations, the reduced APDFSs
      in OB and mebeverine were 0.55 +/- 1.20 (P = 0.011) and 0.37 +/- 1.11 (P =
      0.042), respectively, to show similarly reduced scores. The most reported side
      effects included dry mouth, nausea and dizziness. Besides, the improved APDFSs at
      4th week visit, final alleviations in abdominal pain intensity, flatulence,
      abdominal bloating and satisfied stool frequency with global assessments filled
      by both patients and investigators were significantly achieved by both
      treatments, and OB was not inferior to mebeverine in treating these parameters.
      CONCLUSIONS: In Orientals, OB is as effective as mebeverine for alleviating IBS
      symptoms in terms of abdominal pain, flatulence, abdominal bloating etc. However,
      obvious side effects are also observed. A large-scaled trial and post-marketing
      surveillance are recommended to confirm its efficacy and safety.

PMID- 22148111
TI  - The effects of ginger on gallbladder motility in healthy male humans.
AB  - BACKGROUND/AIMS: Ginger has been used to treat a number of diseases including
      those affecting the digestive tract. This study was aimed to investigate the
      effects of ginger on gallbladder volume and gastrointestinal sensation in healthy
      male subjects. METHODS: Nineteen healthy male volunteers (age 21.3 +/- 3.9 years,
      body mass index 21.6 +/- 1.9 kg/m(2)) were studied on 2 occasions in a double
      blind randomized crossover design. After ingesting ginger (1,200 mg) or placebo
      capsules (starch), abdominal ultrasound was used to measure the gallbladder
      volume (calculated from gallbladder width, depth and diameter) and ejection
      fraction following a standard test meal. Gastrointestinal symptoms were also
      recorded at regular intervals by visual analogue scales. RESULTS: There were no
      differences in gallbladder volume or ejection fraction between ginger and
      placebo. Abdominal symptoms of bloating, fullness, nausea, discomfort and hunger
      was not different between the 2 occasions. CONCLUSIONS: Ginger (1,200 mg) may not
      affect gallbladder ejection fraction and possible relevant abdominal symptoms in
      healthy male human subjects.

PMID- 22148112
TI  - How to interpret a functional or motility test - defecography.
AB  - Defecography evaluates in real time the morphology of rectum and anal canal in a
      physiologic setting by injection of a thick barium paste into the rectum and its
      subsequent evacuation. Because of its ability of structural and functional
      evaluation, defecography is primarily performed for work up of patients with
      longstanding constipation, unexplained anal or rectal pain, residual sensation
      after defecation or suspected prolapse. Technique and interpretation of this
      examination are outlined in this review.

PMID- 22148113
TI  - High-resolution manometry for assessing hiatal hernia in a patient with severe
      reflux esophagitis.

PMID- 22148114
TI  - Intestinal pseudo-obstruction: initial manifestation of systemic lupus
      erythematosus.

PMID- 22148115
TI  - A functional role for the 'fibroblast-like cells' in gastrointestinal smooth
      muscles (J Physiol 2011;589[Pt 3]:697-710).

PMID- 22148116
TI  - Influence of gut microbes on the brain-gut axis (Gut 2011;60:307-317).

PMID- 22148117
TI  - How is the autonomic nerve function different between gastroesophageal reflux
      disease alone and gastroesophageal reflux disease with diabetes mellitus
      neuropathy?

PMID- 22148119
TI  - Do histamine-2 receptor antagonists and proton pump inhibitors really have no
      effect on the gastric emptying rate?

PMID- 22148121
TI  - The epidemiology and cost of surgical site infections in Korea: a systematic
      review.
AB  - PURPOSE: To conduct a systematic literature review of the epidemiological and
      economic burden of surgical site infection (SSI) in Korea. METHODS: A search of
      the EMBASE, Medline and KoreaMed databases for English and Korean language
      publications was conducted. Searches for epidemiological and economic studies
      were conducted separately and limited to 1995 to 2010 to ensure the pertinence of
      the data. RESULTS: Twenty-six studies were included. The overall incidence of SSI
      in Korea was 2.0 to 9.7%. The National Nosocomial Infections Surveillance risk
      index was positively correlated with the risk of developing an SSI. Specific risk
      factors for SSI, identified through multivariate analyses included; diabetes,
      antibiotic prophylaxis and wound classification. SSIs were associated with
      increased hospitalisation cost, with each episode of SSI estimated to cost about
      an additional ?2,000,000. A substantial portion of the increased cost was
      attributed to hospital room costs and the need for additional medication. Studies
      also found that post-operative stays for patients with SSIs were 5 to 20 days
      longer, while two studies reported that following cardiac surgery, patients with
      SSIs spent an additional 5 to 11 days in the intensive care unit, compared to
      patients without SSIs. CONCLUSION: Data from the included studies demonstrate
      that SSI represents a significant clinical and economic burden in Korea.
      Consequently, the identification of high-risk patient populations and the
      development of strategies aimed at reducing SSI may lead to cost-savings for the
      healthcare system.

PMID- 22148122
TI  - A missense polymorphism (rs11895564, Ala380Thr) of integrin alpha 6 is associated
      with the development and progression of papillary thyroid carcinoma in Korean
      population.
AB  - PURPOSE: Integrins play crucial roles in the pathogenesis of papillary thyroid
      carcinoma (PTC). The aim of this study was to investigate whether two single
      nucleotide polymorphisms (SNPs) (rs2141698, -1687A/G; rs11895564, Ala380Thr) of
      the integrin alpha 6 (ITGA6) gene are associated with the development and
      clinicopathologic characteristics of PTC such as the size (<1 cm and >=1 cm),
      number (unifocality and multifocality), location (one lobe and both lobes),
      extrathyroid invasion, and cervical lymph node metastasis. METHODS: We enrolled
      104 PTC patients and 318 control subjects. Genotypes of each SNP were determined
      by direct sequencing. SNPStats, SNPAnalyzer, and Helixtree programs were used to
      evaluate odds ratios (ORs), 95% confidence intervals (CIs), and P-values.
      Multiple logistic regression models were performed to analyze genetic data.
      RESULTS: A missense SNP rs11895564 was associated with the development of PTC.
      The A allele frequency of rs11895564 was higher in PTC patients than in controls
      (13.5% vs. 7.1%; P = 0.005; OR, 2.04; 95% CI, 1.24 to 3.37). In the
      clinicopathologic characteristics, the A allele frequency of rs11895564 showed
      difference in the size (19.6% in <1 cm vs. 6.9% in >=1 cm; P = 0.010; OR, 0.30;
      95% CI, 0.12 to 0.75) and number (8.5% in unifocality vs. 20.8% in multifocality;
      P = 0.015; OR, 2.85; 95% CI, 1.23 to 6.59) of PTC. CONCLUSION: These results
      suggest that the A allele of rs11895564 (Ala380Thr) in ITGA6 may be a risk factor
      of PTC, and also contribute to the progression of PTC in the Korean population.

PMID- 22148123
TI  - Coexistence of parathyroid adenoma and papillary thyroid carcinoma.
AB  - PURPOSE: Although several reports have been published regarding the coexistence
      of hyperparathyroidism and papillary thyroid carcinomas, concurrence of
      parathyroid adenoma and papillary thyroid carcinoma is extremely rare. The aim of
      this study was to describe experiences with concurrent parathyroid adenoma and
      papillary thyroid carcinoma. METHODS: Seven patients with concurrent parathyroid
      adenoma and papillary thyroid carcinoma were identified between January 2006 and
      December 2007, and their medical records were reviewed retrospectively. RESULTS:
      Of the seven patients identified, three were male and four were female; their
      mean age was 53.6 years. None of the patients presented with symptomatic
      hyperparathyroidism preoperatively. On laboratory findings, four patients had
      mild to moderate hypercalcemia, but serum parathyroid hormone concentrations were
      high in all patients. Preoperative imaging showed suspicious features of diseased
      parathyroid glands in four patients; two upon ultrasonography and computed
      tomography together and two upon ultrasonography only. The coexistence of
      parathyroid adenoma did not affect the extent of thyroid surgery. Laboratory
      values after surgery returned to within normal ranges in all patients.
      CONCLUSION: It is important not only to analyze serum calcium levels but also to
      carefully interpret imaging studies in order to identify asymptomatic
      hyperparathyroidism when performing thyroid cancer surgery.

PMID- 22148124
TI  - Comparison of clinical outcomes and hospital cost between open appendectomy and
      laparoscopic appendectomy.
AB  - PURPOSE: Laparoscopic appendectomy has been recognized to have many advantages
      such as greater cosmetic results, less postoperative pain and shorter hospital
      stays. On the other hand, the cost of laparoscopic procedures is still more
      expensive than that of open procedures in Korea. The aim of this study is to
      compare clinical outcomes and hospital costs between open appendectomy and
      laparoscopic appendectomy. METHODS: Between January 1, 2010 and December 31,
      2010, 471 patients were diagnosed with acute appendicitis. Of these, 418 patients
      met the inclusion criteria and were divided into two groups of open appendectomy
      (OA) group and laparoscopic appendectomy (LA) group. We analyzed the clinical
      data and hospital costs. RESULTS: The mean operation time for laparoscopic
      appendectomy (72.17 minutes) was significantly longer than that of open
      appendectomy (46.26 minutes) (P = 0.0004). The mean amounts of intravenous
      analgesics for OA group (2.00 times) was greater than that of LA group (1.86
      times) (P < 0.0001). The complication rate was similar between the two groups
      (OA, 6.99% vs. LA, 10.87%; P = 0.3662). The mean length of postoperative hospital
      stay was shorter in LA group (OA, 4.55 days vs. LA, 3.60 days; P = 0.0002). The
      mean total cost covered by the National Health Insurance was more expensive in LA
      group (OA, 1,259,842 won [Korean monetary unit] vs. LA, 1,664,367 won; P =
      0.0057). CONCLUSION: Clinical outcomes of laparoscopic appendectomy were superior
      to that of open appendectomy even though the cost of laparoscopic appendectomy
      was more expensive than that of open appendectomy. Whenever surgeons manage a
      patient with appendicitis, laparoscopic appendectomy should be considered as the
      procedure of choice.

PMID- 22148125
TI  - Comparative analysis of summary scoring systems in measuring fecal incontinence.
AB  - PURPOSE: For measuring symptoms of fecal incontinence, summary scoring systems
      are widely used, but rigorous psychometric validation or assessment of such
      systems in terms of patients' subjective perception has rarely been done to date.
      This study was designed to assess the correlation between each severity measure
      and patients' subjective perception or clinicians' clinical assessment. We
      attempted to compare summary scoring systems of severity measures and searched
      for which of them showed higher validity among them. METHODS: Consecutive
      patients who visited our clinic with fecal incontinence were prospectively
      evaluated. A total of 43 patients were included. Four summary scoring systems
      were chosen for comparison: the Rothenberger, Wexner, Vaizey and Fecal
      Incontinence Severity Index systems. They are correlated with subjective
      perception scores by patients, and also with clinical assessment scores by
      investigators. RESULTS: There was no significant difference between clinical
      scores of two investigators (paired t-test, P = 0.988). Inter-observer
      reliability was 0.95 (Intra-class correlation coefficient, 95% confidence
      interval 0.91 to 0.98). Significant correlations were proved between patients'
      subjective perception scores and all the summary scoring systems, and also
      between the mean clinical scores and all the summary scoring systems. The highest
      was with the Wexner scale (r = 0.66, P < 0.001) (r = 0.70, P < 0.001), and the
      lowest was with the Rothenberger scale (r = 0.58, P < 0.001) (r = 0.61, P <
      0.001) in both correlations. CONCLUSION: The Wexner scale correlates the most
      closely with subjective perception of severity of symptoms by patients, and also
      with clinical assessment by investigators. We recommend the Wexner scale among
      summary scoring systems as a tool for measuring fecal incontinence.

PMID- 22148126
TI  - An easy and secure pancreaticogastrostomy after pancreaticoduodenectomy:
      transpancreatic suture with a buttress method through an anterior gastrotomy.
AB  - PURPOSE: The aim of this report was to describe a new reconstructive technique of
      pancreaticogastrostomy and to also discuss this procedure's effectiveness for
      reducing the incidence of postoperative complications. METHODS: We
      retrospectively analyzed early surgical outcomes in 21 consecutive patients who
      underwent this novel pancreaticogastrostomy after pancreaticoduodenectomy.
      Pancreaticogastrostomy was completed with 2 transpancreatic sutures with
      buttresses on both the upper and lower edges of the implanted pancreas through
      the retracted anterior gastrotomy. RESULTS: Operative mortality was zero and
      morbidity was 23.8%. A significant pancreatic fistula occurred in 1 patient
      (4.7%; grade B). CONCLUSION: This technique is very easy to perform, less
      traumatic to the pancreatic stump, can be performed through a mini-laparotomy due
      to good vision and straight sutures, and it is secure owing to anchoring of the
      invaginated pancreatic stump to the stomach's posterior wall with buttresses. The
      results of this pilot study indicate that the technique may provide a favorable
      outcome and could be an alternative method of pancreatoenteric anastomosis.
      However, to determine its superiority over the conventional procedures, this
      operative technique should be evaluated more comprehensively in a larger series.

PMID- 22148127
TI  - Initial experience of single port laparoscopic totally extraperitoneal hernia
      repair: nearly-scarless inguinal hernia repair.
AB  - PURPOSE: In the early 1990's laparoscopic hernioplasty gained popularity
      worldwide. Thereafter, laparoscopic surgeons have attempted to improve cosmesis
      using single port surgery. This study aims to introduce and assess the safety and
      feasibility of single port laparoscopic total extraperitoneal (TEP) hernia repair
      with a nearly-scarless umbilical incision. METHODS: Sixty three single port
      laparoscopic TEP hernia repairs were performed in sixty patients from June 2010
      to March 2011 at Incheon St. Mary's Hospital, with the use of a glove single-port
      device and standard laparoscopic instruments. Demographic and clinical data,
      intraoperative findings, and postoperative course were reviewed. RESULTS: Of the
      63 hernias treated, 31 were right inguinal hernias, 26 were left inguinal hernias
      and 3 were both inguinal hernias. There was one conversion to conventional three
      port laparoscopic transabdominal preperitoneal hernioplasty. Mean operative time
      was 62 minutes (range, 32 to 150 minutes). There were no intraoperative
      complications. Postoperative complications occurred in two cases (wound seroma
      and urinary retension) and were successfully treated conservatively. Mean
      hospital stay was 2.15 days. CONCLUSION: Single port laparoscopic TEP hernia
      repair is safe and feasible. Umbilical incision provides an excellent cosmetic
      outcome. Prospective randomized studies comparing single port and conventional
      three port laparoscopic TEP repairs with short-term outcome and long-term
      recurrence rate are needed for confirmation.

PMID- 22148128
TI  - Hungry bone syndrome after parathyroidectomy of a minimally invasive parathyroid
      carcinoma.
AB  - The prognosis of parathyroid carcinoma varies significantly between numerous
      studies. Therefore, many attempts have been made to grade the degree of
      parathyroid carcinoma, and recently, classifying parathyroid carcinomas into
      either minimally invasive or widely invasive carcinoma- similar to follicular
      carcinoma of the thyroid- has led to a more reliable prediction of the prognosis.
      Hungry bone syndrome can occur if parathyroidectomy is performed due to primary
      hyperparathyroidism regardless of the cause of the disease. Hungry bone syndrome
      is characterized by postoperative a hypocalcemic state due to remineralization of
      various minerals, including calcium, of the bone; this syndrome requires a long
      term supplementation of calcium. The authors aim to report, along with a review
      of related literatures, 1 case of a 29-year-old female patient diagnosed with
      minimally invasive parathyroid carcinoma who fell into hungry bone syndrome after
      parathyroidectomy.

PMID- 22148129
TI  - Intractable rectal stricture caused by hot water enema.
AB  - Rectal burns caused by hot water enema have been reported only occasionally and
      the majority of them were treated in a conservative manner. Although intractable
      rectal stricture caused by rectal burn is rare, it may be treated by endoscopic
      intervention or surgery. A 52-year-old woman who had used various methods of
      enema to treat her chronic constipation eventually undertook a hot water enema
      herself. After that, anal pain and constipation became aggravated prompting her
      to visit our clinic. Although various nonoperative treatments including
      endoscopic stenting were performed, her obstructive symptom did not improve and
      endoscopic findings had not changed. Hence, we performed a laparoscopic
      proctosigmoidectomy and transanal coloanal anastomosis with ileal diversion to
      treat the disease, and as a result, her obstructive symptom improved well.
      Corrective surgery such as resection of involved segment with anastomosis may be
      beneficial in relieving obstructive symptoms of an intractable rectal stricture
      caused by hot water enema.

PMID- 22148130
TI  - Robotic pylorus preserving pancreaticoduodenectomy with mini-laparotomy
      reconstruction in patient with ampullary adenoma.
AB  - Robotic surgical system provides many unique advantages which might compensate
      the limitations of usual laparoscopic surgery. By using robotic surgical system,
      we performed robot-assisted laparoscopic pancreaticoduodenectomy (PD). A Sixty
      two year old female patient with an ampullary mass underwent robot assisted PD
      due to imcomplete treatment of endoscopic ampullectomy. The removal of specimen
      and reconstruction were performed through small upper midline skin incision.
      Robot working time was about 8 hours, and blood loss was about 800 ml without
      blood transfusion. She returned to an oral diet on postoperative day 3. Grade B
      pancreatic leak was noted during the postoperative period, but was successfully
      managed by conservative management alone. We successfully performed da Vinci
      assisted laparoscopic PD, and robot surgical system provided three-dimensional
      stable visualization and wrist-like motion of instrument facilitated complex
      operative procedures. More experiences are necessary to address real role of
      robot in far advanced laparoscopic pancreatic surgery.

PMID- 22148131
TI  - Splenic infarction as a complication of celiac artery thromboembolism: an unusual
      cause of abdominal pain.
AB  - Splenic infarction is a relatively uncommon diagnosis and this clinical
      presentation can mimic other causes of acute abdominal pain. Cardiologic and
      hematologic disorders are common reasons for this entity. There have been a few
      series and single case reports of splenic infarction published in peer-reviewed
      medical journals. We report a 53-year-old patient who had splenic infarction
      caused by celiac artery thromboembolism. The importance of this case, without any
      etiological predisposing factors, is that this kind of clinical situation should
      be considered in the differential diagnosis of abdominal pain.

PMID- 22148132
TI  - Why do mothers breastfeed girls less than boys? Evidence and implications for
      child health in India.
AB  - Breastfeeding is negatively correlated with future fertility because nursing
      temporarily reduces fecundity and because mothers usually wean on becoming
      pregnant again. We model breastfeeding under son-biased fertility preferences and
      show that breastfeeding duration increases with birth order, especially near
      target family size; is lowest for daughters and children without older brothers
      because their parents try again for a son; and exhibits the largest gender gap
      near target family size, when gender is most predictive of subsequent fertility.
      Data from India confirm each prediction. Moreover, child survival exhibits
      similar patterns, especially in settings where the alternatives to breastmilk are
      unsanitary.

PMID- 22148133
TI  - Competition and product quality in the supermarket industry.
AB  - This article analyzes the effect of competition on a supermarket firm's incentive
      to provide product quality. In the supermarket industry, product availability is
      an important measure of quality. Using U.S. Consumer Price Index microdata to
      track inventory shortfalls, I find that stores facing more intense competition
      have fewer shortfalls. Competition from Walmart-the most significant shock to
      industry market structure in half a century-decreased shortfalls among large
      chains by about a third. The risk that customers will switch stores appears to
      provide competitors with a strong incentive to invest in product quality.

PMID- 22148134
TI  - Black churches and HIV/AIDS: factors influencing congregations' responsiveness to
      social issues.
AB  - The ambivalent response of many black churches to current social issues has
      caused some scholars to question the centrality of black churches within African
      American communities. Using a nationally representative sample of black
      congregations, this study engages the debate about the institutional centrality
      of black churches by focusing on their response to HIV/AIDS. Although many
      congregational studies treat black churches as a monolithic whole, this analysis
      identifies heterogeneity among black churches that shapes their responsiveness to
      social issues. Contrary to prior claims, a congregation's liberal-conservative
      ideological orientation does not significantly affect its likelihood of having an
      HIV/AIDS program. Beyond assessing churches' internal characteristics, this study
      uses institutional theory to analyze churches as open systems that can be
      influenced by their surrounding environment. It demonstrates that externally
      engaged congregations are significantly more likely to have a program. These
      results indicate that black churches maintain institutional centrality by
      engaging their external environment.

PMID- 22148136
TI  - Abstracts of the British Fertility Society Annual Meeting. January 5-7, 2012.

PMID- 22148135
TI  - Religiosity, psychological resources, and physical health.
AB  - Various explanations have been given for the positive association between
      religiosity and physical health. Using data from two waves of the National Survey
      of Midlife in the United States (1995, 2005) and retrospective data on the
      importance of religion in the home in which respondents were raised we find that
      psychological resources, operationalized by measures of emotional and
      psychological well-being, mediate the effect of this early exposure to religion
      but only on self-rated health and physical symptomatology; chronic illnesses and
      health limitations on activities of daily living are unaffected.

PMID- 22148138
TI  - [Neurologic aspects of holoprosencephaly].

PMID- 22148137
TI  - James Harold Dobyns, MD.

PMID- 22148139
TI  - [New aspects of neurobiology of migraine: the role of hypothalamic-pineal
      system].

PMID- 22148140
TI  - [Internet addictive behaviour].

PMID- 22148141
TI  - Introduction to Larry Needham issue.

PMID- 22148142
TI  - Larry Needham and the partition ratio.

PMID- 22148143
TI  - Abstracts of the Australasian Professional Society on Alcohol and Other Drugs
      Conference, November 13-16, 2011. Hobart, Australia.

PMID- 22148144
TI  - Iodine deficiency causing stillbirths and deaths among suckler calves.

PMID- 22148146
TI  - Abstracts of the 17th North American Regional ISSX International Society for the
      Study of Xenobiotics) Meeting. October 16-20, 2011. Atlanta, Georgia, USA.

PMID- 22148147
TI  - Abstracts of the AAGBI (Association of Anaesthetists of Great Britain and
      Ireland) Annual Congress. September 21-23, 2011. Edinburgh, Scotland, United
      Kingdom.

PMID- 22148145
TI  - Is the first cut the deepest? Ernst Engel on the statistical imperative of
      embracing the lifecourse perspective.

PMID- 22148148
TI  - Bringing perspective to illicit markets: estimating the size of the U.S.
      marijuana market.

PMID- 22148149
TI  - Abstracts of the 12th Iranian Congress of Biochemistry & 4th International
      Congress of Biochemistry and Molecular Biology. Mashhad, Iran. September 6-9,
      2011.

PMID- 22148151
TI  - Ground-truth data cannot do it alone.

PMID- 22148150
TI  - Pentalogy of Cantrell demonstrated by computed tomography in an infant.

PMID- 22148152
TI  - Paul Tesar.

PMID- 22148153
TI  - Salience to relevance.

PMID- 22148154
TI  - Yeast 2.0.

PMID- 22148155
TI  - One stem cell at a time.

PMID- 22148156
TI  - Picking up the pieces.

PMID- 22148157
TI  - Molecular matchmaking for neural control.

PMID- 22148159
TI  - Mesoporous nitrogen-doped carbon-glass ceramic cathodes for solid-state lithium
      oxygen batteries.
AB  - The composite of nitrogen-doped carbon (N-C) blend with lithium aluminum
      germanium phosphate (LAGP) was studied as cathode material in a solid-state
      lithium-oxygen cell. Composite electrodes exhibit high electrochemical activity
      toward oxygen reduction. Compared to the cell capacity of N-C blend cathode, N
      C/LAGP composite cathode exhibits six times higher discharge cell capacity. A
      significant enhancement in cell capacity is attributed to higher electrocatalytic
      activity and fast lithium ion conduction ability of LAGP in the cathode.

PMID- 22148160
TI  - Gallium(III) triflate: an efficient and a sustainable Lewis acid catalyst for
      organic synthetic transformations.
AB  - Green chemical processes play a crucial role in sustainable development, and
      efficient recyclable catalysts that can be conveniently applied in various
      chemical reactions are the key elements for the development of sustainable
      synthetic processes. Many organic transformations rely on Lewis and Bronsted acid
      catalysts, and such molecules have been widely studied in organic synthesis. Over
      the years, researchers have looked for Lewis acid catalysts that provide high
      selectivity and high turnover frequency but are also stable in aqueous media and
      recoverable. Since the first preparation of trifluoromethanesulfonic acid by
      Hazeldine (triflic acid, HOTf), researchers have synthesized and used numerous
      metal triflates in a variety of organic reactions. Even though the rare earth
      metal triflates have played a major role in these studies, the majority of rare
      earth triflates lack one or more of the primary properties of sustainable
      catalysts: low cost and easy availability of the metals, easy preparation of
      triflates, aqueous/thermal stability, recyclability, and catalytic efficiency. 
      In this Account, we describe the synthetic applications of Ga(OTf)(3) and its
      advantages over similar catalysts. Ga(OTf)(3) can be conveniently prepared from
      gallium metal or gallium chloride in excess of trifluoromethanesulfonic acid
      (triflic acid) under reflux. Among many Lewis acid catalysts recently studied,
      Ga(OTf)(3) is water tolerant and soluble and requires very low catalyst loading
      to drive various acid-catalyzed reactions including Friedel-Crafts alkylation,
      hydroxyalkylation, and acylation selectively and efficiently. In many reactions
      Ga(OTf)(3) demonstrated high chemo- and regioselectivity, high yields, excellent
      stability, and recyclability. We successfully synthesized many biologically
      active heterocycles and their fluoroanalogs under mild conditions. Many
      challenging reactions such as the ketonic Strecker reactions proceed efficiently
      via Ga(OTf)(3) catalysis. Because it is stable in water, this catalyst provides
      the opportunity to study substrates and develop new synthetic protocols in
      aqueous media, significantly reducing the production of hazardous waste from
      organic solvents and toxic catalyst systems.

PMID- 22148158
TI  - Searching for DNA lesions: structural evidence for lower- and higher-affinity DNA
      binding conformations of human alkyladenine DNA glycosylase.
AB  - To efficiently repair DNA, human alkyladenine DNA glycosylase (AAG) must search
      the million-fold excess of unmodified DNA bases to find a handful of DNA lesions.
      Such a search can be facilitated by the ability of glycosylases, like AAG, to
      interact with DNA using two affinities: a lower-affinity interaction in a
      searching process and a higher-affinity interaction for catalytic repair. Here,
      we present crystal structures of AAG trapped in two DNA-bound states. The lower
      affinity depiction allows us to investigate, for the first time, the conformation
      of this protein in the absence of a tightly bound DNA adduct. We find that active
      site residues of AAG involved in binding lesion bases are in a disordered state.
      Furthermore, two loops that contribute significantly to the positive
      electrostatic surface of AAG are disordered. Additionally, a higher-affinity
      state of AAG captured here provides a fortuitous snapshot of how this enzyme
      interacts with a DNA adduct that resembles a one-base loop.

PMID- 22148161
TI  - Enhanced Gaussia luciferase blood assay for monitoring of in vivo biological
      processes.
AB  - Secreted Gaussia luciferase (Gluc) has been shown to be a useful tool for ex vivo
      monitoring of in vivo biological processes. The Gluc level in the blood was used
      to detect tumor growth, metastasis and response to therapy, gene transfer, and
      circulating cells viability, as well as transcription factors activation,
      complementing in vivo bioluminescence imaging. The sensitivity of the Gluc blood
      assay is limited due to the absorption of blue light by pigmented molecules such
      as hemoglobin, resulting in quenching of the signal and therefore lower
      sensitivity. To overcome this problem, we designed an alternative microtiter well
      based binding assay in which Gluc is captured first from blood using a specific
      antibody followed by the addition of coelenterazine and signal acquisition using
      a luminometer. This assay showed to be over 1 order of magnitude more sensitive
      in detecting Gluc in the blood as compared to the direct Gluc blood assay
      enhancing ex vivo monitoring of biological processes.

PMID- 22148162
TI  - Mechanical and environmental stability of polymer thin-film-coated graphene.
AB  - A uniform polymer thin layer of controllable thickness was bar-coated onto a
      chemical vapor deposition (CVD) grown monolayer graphene surface. The effects of
      this coating layer on the optical, electric, and tribological properties were
      then investigated. The thin polymer coating layer did not reduce the optical
      transmittance of the graphene films. The variation in the sheet resistance of the
      graphene films after the coating depended on the interaction between polymer and
      graphene. The top coating layer can maintain the high conductivity of chemical
      doped graphene films under long-term ambient conditions compared with uncovered
      doped samples. Friction tests demonstrated that the polymer coating layer can
      enhance both the friction force and the coefficient of friction of the graphene
      films and protect the graphene against damage in the repeated sliding processes.

PMID- 22148163
TI  - Genome-wide bacterial toxicity screening uncovers the mechanisms of toxicity of a
      cationic polystyrene nanomaterial.
AB  - By exploiting a genome-wide collection of bacterial single-gene deletion mutants,
      we have studied the toxicological pathways of a 60-nm cationic (amino
      functionalized) polystyrene nanomaterial (PS-NH(2)) in bacterial cells. The
      IC(50) of commercially available 60 nm PS-NH(2) was determined to be 158 MUg/mL,
      the IC(5) is 108 MUg/mL, and the IC(90) is 190 MUg/mL for the parent E. coli
      strain of the gene deletion library. Over 4000 single nonessential gene deletion
      mutants of Escherichia coli were screened for the growth phenotype of each strain
      in the presence and absence of PS-NH(2). This revealed that genes clusters in the
      lipopolysaccharide biosynthetic pathway, outer membrane transport channels,
      ubiquinone biosynthetic pathways, flagellar movement, and DNA repair systems are
      all important to how this organism responds to cationic nanomaterials. These
      results, coupled with those from confirmatory assays described herein, suggest
      that the primary mechanisms of toxicity of the 60-nm PS-NH(2) nanomaterial in E.
      coli are destabilization of the outer membrane and production of reactive oxygen
      species. The methodology reported herein should prove generally useful for
      identifying pathways that are involved in how cells respond to a broad range of
      nanomaterials and for determining the mechanisms of cellular toxicity of
      different types of nanomaterials.

PMID- 22148166
TI  - Pore shape of honeycomb-patterned films: modulation and interfacial behavior.
AB  - The control of the pore size of honeycomb-patterned films has been more or less
      involved in most work on the topic of breath figures. Modulation of the pore
      shape was largely ignored, although it is important to applications in replica
      molding, filtration, particle assembly, and cell culture. This article reports a
      tunable pore shape for patterned films prepared from commercially available
      polystyrene (PS). We investigated the effects of solvents including
      tetrahydrofuran (THF) and chloroform (CF) and hydrophilic additives including
      poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), poly(ethylene glycol) (PEG),
      and poly(N-vinyl pyrrolidone) (PVP). Water droplets on/in the polymer solutions
      were observed and analyzed for simulating the formation and stabilization of
      breath figures. Interfacial tensions of the studied systems were measured and
      considered as a main factor to modulate the pore shape. Results indicate that the
      pores gradually change from near-spherical to ellipsoidal with the increase of
      additive content when using CF as the solvent; however, only ellipsoidal pores
      are formed from the THF solution. It is demonstrated that the aggregation of the
      additives at the water/polymer solution interface is more efficient in the THF
      solution than that in the CF solution. This aggregation decreases the interfacial
      tension, stabilizes the condensed water droplets, and shapes the pores of the
      films. The results may facilitate our understanding of the dynamic breath figure
      process and provide a new pathway to prepare patterned films with different pore
      structures.

PMID- 22148167
TI  - Sesamolinol glucoside, disaminyl ether, and other lignans from sesame seeds.
AB  - The application of a procedure based on XAD-4 adsorption resin permitted the
      obtainment of an enriched polyphenolic extract from Sesamum indicum seeds.
      Chemical analysis of the obtained extract led to the identification of 12
      lignans. Among them, 2 lignans, (+)-sesamolinol-4'-O-beta-D-glucoside and
      disaminyl ether, are reported for the first time as natural compounds. Their
      structure has been determined by spectroscopic methods, mainly by the application
      of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR)
      techniques [heteronuclear multiple-quantum coherence (HMQC), heteronuclear
      multiple-bond correlation (HMBC), and nuclear Overhauser effect spectrometry
      (NOESY)] and mass spectroscopy. The isolated compounds were evaluated for their
      antimutagenic activity. Among the tested lignans, the most active lignan was
      found to be sesamolin, followed by sesamolinol and samin, against H(2)O(2).
      Additionally, some of the tested lignans showed desmutagenic activity against
      benzo[a]pyrene (BaP).

PMID- 22148168
TI  - How alkali metal ion binding alters the conformation preferences of gramicidin A:
      a molecular dynamics and ion mobility study.
AB  - Here, we present a systematic study combing electrospray ionization-ion mobility
      experiments and an enhanced sampling molecular dynamics, specifically integrated
      tempering sampling molecular dynamics simulations (ITS-MDS), to explore the
      conformations of alkali metal ion (Na, K, and Cs) adducts of gramicidin A (GA) in
      vacuo. Folding simulation is performed to obtain inherent conformational
      preferences of neutral GA to provide insights about how the binding of metal ions
      influences the intrinsic conformations of GA. The comparison between
      conformations of neutral GA and alkali metal ion adducts reveals a high degree of
      structural similarity, especially between neutral GA and [GA + Na](+); however,
      the structural similarities decrease as ionic radius of the metal increases.
      Collision cross section (CCS) profiles for [GA + Na](+) and [GA + Cs](+) ions
      obtained from by ITS-MDS compare favorably with the experimental CCS, but there
      are significant differences from CCS profiles for [GA + K](+) ions. Such
      discrepancies between the calculated and measured CCS profiles for [GA + K](+)
      are discussed in terms of limitations in the simulation force field as well as
      possible size-dependent coordination of the [GA + K](+) ion complex.

PMID- 22148169
TI  - Direct comparison of solution and gas-phase reactions of the three distonic
      isomers of the pyridine radical cation with methanol.
AB  - To directly compare the reactivity of positively charged carbon-centered aromatic
      sigma-radicals toward methanol in solution and in the gas phase, the 2-, 3-, and
      4-dehydropyridinium cations (distonic isomers of the pyridine radical cation)
      were generated by ultraviolet photolysis of the corresponding iodo precursors in
      a mixture of water and methanol at varying pH. The reaction mixtures were
      analyzed by using liquid chromatography/mass spectrometry. Hydrogen atom
      abstraction was the only reaction observed for the 3- and 4-dehydropyridinium
      cations (and pyridines) in solution. This also was the major reaction observed
      earlier in the gas phase. Depending on the pH, the hydrogen atom can be
      abstracted from different molecules (i.e., methanol or water) and from different
      sites (in methanol) by the 3- and 4-dehydropyridinium cations/pyridines in
      solution. In the pH range 1-4, the methyl group of methanol is the main hydrogen
      atom donor site for both 3- and 4-dehydropyridinium cations (just like in the gas
      phase). At higher pH, the hydroxyl groups of water and methanol also act as
      hydrogen atom donors. This finding is rationalized by a greater abundance of the
      unprotonated radicals that preferentially abstract hydrogen atoms from the polar
      hydroxyl groups. The percentage yield of hydrogen atom abstraction by these
      radicals was found to increase with lowering the pH in the pH range 1.0-3.2. This
      pH effect is rationalized by polar effects: the lower the pH, the greater the
      fraction of protonated (more polar) radicals in the solution. This finding is
      consistent with previous results obtained in the gas phase and suggests that gas
      phase studies can be used to predict solution reactivity, but only as long as the
      same reactive species is studied in both experiments. This was found not to be
      the case for the 2-iodopyridinium cation. Photolysis of this precursor in
      solution resulted in the formation of two major addition products, 2-hydroxy- and
      2-methoxypyridinium cations, in addition to the hydrogen atom abstraction
      product. These addition products were not observed in the earlier gas-phase
      studies on 2-dehydropyridinium cation. Their observation in solution is explained
      by the formation of another reactive intermediate, the 2-pyridylcation, upon
      photolysis of 2-iodopyridinium cation (and 2-iodopyridine). The same intermediate
      was observed in the gas phase but it was removed before examining the reactions
      of the desired radical, 2-dehydropyridinium cation (which cannot be done in
      solution).

PMID- 22148170
TI  - Enhancing the coverage of the urinary metabolome by sheathless capillary
      electrophoresis-mass spectrometry.
AB  - Sheathless capillary electrophoresis-mass spectrometry (CE-MS), using a porous
      tip sprayer, is proposed for the first time for highly sensitive metabolic
      profiling of human urine. A representative metabolite mixture and human urine
      were used for evaluation of the sheathless CE-MS platform. For test compounds,
      relative standard deviations (RSDs) for migration times and peak areas were below
      2% and 12%, respectively, and an injection volume of only ~8 nL resulted in
      detection limits between 11 and 120 nM. Approximately 900 molecular features were
      detected in human urine by sheathless CE-MS whereas about 300 molecular features
      were found with classical sheath-liquid CE-MS. This difference can probably be
      attributed to an improved ionization efficiency and increased sensitivity at low
      flow-rate conditions. The integration of transient-isotachophoresis (t-ITP) as an
      in-capillary preconcentration procedure in sheathless CE-MS further resulted in
      subnanomolar limits of detection for compounds of the metabolite mixture, and
      more than 1300 molecular features were observed in urine. Compared to the
      classical CE-MS approaches, the integration of t-ITP combined with the use of a
      sheathless interface provides up to 2 orders of magnitude sensitivity
      improvement. Hence, sheathless CE-MS can be used for in-depth metabolic profiling
      of biological samples, and we anticipate that this approach will yield unique
      information in the field of metabolomics.

PMID- 22148171
TI  - Stereoselective synthesis of 2,6-cis-substituted tetrahydropyrans: Bronsted acid
      catalyzed intramolecular oxa-conjugate cyclization of alpha,beta-unsaturated
      ester surrogates.
AB  - Intramolecular oxa-conjugate cyclization (IOCC) of alpha,beta-unsaturated
      carbonyl compounds, triggered by deprotonation with a base, represents a
      straightforward method for the synthesis of tetrahydropyrans. However, it has
      been known that stereochemical outcome of IOCC depends on the local structure of
      substrates and sometimes requires harsh reaction conditions and/or prolonged
      reaction times for selective formation of 2,6-cis-substituted tetrahydropyrans.
      These shortcomings limit the feasibility of IOCC in the context of complex
      natural product synthesis. In this paper, we describe Bronsted acid-catalyzed
      IOCC of alpha,beta-unsaturated ester surrogates (e.g., alpha,beta-unsaturated
      thioesters, oxazolidinone imides, and pyrrole amides) under mild reaction
      conditions, which affords a series of synthetically versatile 2,6-cis-substituted
      tetrahydropyran derivatives with good to excellent stereoselectivity (dr from 7:1
      to >20:1). These alpha,beta-unsaturated carbonyl compounds were found to be more
      reactive than the corresponding oxoesters that are generally unreactive toward
      Bronsted acid-catalyzed intramolecular oxa-conjugate additions. The product
      tetrahydropyrans could be transformed into various derivatives in an efficient
      manner, highlighting the usefulness of our methodology.

PMID- 22148175
TI  - Asking questions and appreciating inquiry: a winning strategy for the nurse
      educator and professional nurse learner.
AB  - This article explores "asking questions" as an effective teaching-learning
      strategy and endorses a culture that facilitates asking questions to promote
      ethical and clinical reasoning to keep patients safe and improve care. Nurse
      educators who appreciate the use of empowering, thoughtful questions in
      provocative ways can encourage learners to become astute thinkers and innovative
      problem solvers. Asking questions teaches learners to argue their thoughts,
      ideas, and decisions persuasively and ultimately to realize that is it not the
      right answer that counts as much as asking the right question.

PMID- 22148173
TI  - Identification of novel alpha4beta2-nicotinic acetylcholine receptor (nAChR)
      agonists based on an isoxazole ether scaffold that demonstrate antidepressant
      like activity.
AB  - There is considerable evidence to support the hypothesis that the blockade of
      nAChR is responsible for the antidepressant action of nicotinic ligands. The
      nicotinic acetylcholine receptor (nAChR) antagonist, mecamylamine, has been shown
      to be an effective add-on in patients that do not respond to selective serotonin
      reuptake inhibitors. This suggests that nAChR ligands may address an unmet
      clinical need by providing relief from depressive symptoms in refractory
      patients. In this study, a new series of nAChR ligands based on an isoxazole
      ether scaffold have been designed and synthesized for binding and functional
      assays. Preliminary structure-activity relationship (SAR) efforts identified a
      lead compound 43, which possesses potent antidepressant-like activity (1 mg/kg,
      IP; 5 mg/kg, PO) in the classical mouse forced swim test. Early stage absorption,
      distribution, metabolism, excretion, and toxicity (ADME-Tox) studies also
      suggested favorable drug-like properties, and broad screening toward other common
      neurotransmitter receptors indicated that compound 43 is highly selective for
      nAChRs over the other 45 neurotransmitter receptors and transporters tested.

PMID- 22148174
TI  - Predicting three-dimensional structures of transmembrane domains of beta-barrel
      membrane proteins.
AB  - beta-Barrel membrane proteins are found in the outer membrane of gram-negative
      bacteria, mitochondria, and chloroplasts. They are important for pore formation,
      membrane anchoring, and enzyme activity. These proteins are also often
      responsible for bacterial virulence. Due to difficulties in experimental
      structure determination, they are sparsely represented in the protein structure
      databank. We have developed a computational method for predicting structures of
      the transmembrane (TM) domains of beta-barrel membrane proteins. Based on
      physical principles, our method can predict structures of the TM domain of beta
      barrel membrane proteins of novel topology, including those from eukaryotic
      mitochondria. Our method is based on a model of physical interactions, a discrete
      conformational state space, an empirical potential function, as well as a model
      to account for interstrand loop entropy. We are able to construct three
      dimensional atomic structure of the TM domains from sequences for a set of 23
      nonhomologous proteins (resolution 1.8-3.0 A). The median rmsd of TM domains
      containing 75-222 residues between predicted and measured structures is 3.9 A for
      main chain atoms. In addition, stability determinants and protein-protein
      interaction sites can be predicted. Such predictions on eukaryotic mitochondria
      outer membrane protein Tom40 and VDAC are confirmed by independent mutagenesis
      and chemical cross-linking studies. These results suggest that our model captures
      key components of the organization principles of beta-barrel membrane protein
      assembly.

PMID- 22148176
TI  - A spotlight on strategies for increasing safety reporting in nursing education.
AB  - Health care policy changes have ripple effects that touch many different areas of
      the health care arena. Quality and safety are at the forefront of this
      discussion. In health care institutions, error reporting is expected to monitor
      and improve patient safety. Procedures are in place for reporting errors.
      However, multiple barriers lead to low use of reporting methods. Creating a
      reporting system that leads to transparency could positively affect the health
      care system. Introducing nurses to error reporting at the beginning of their
      educational experience could lead to a reduction in barriers to error reporting
      and promote error reporting. This article discusses strategies to increase error
      and near-miss reporting in a school of nursing.

PMID- 22148179
TI  - Effect of cholesterol on binding of amphipathic helices to lipid emulsions.
AB  - Plasma triglyceride-rich lipoproteins vary in their lipid composition during
      metabolism. We investigated the effects of cholesterol (Chol) on the surface
      properties of lipid emulsions and on the interactions with two amphipathic
      peptides, acetyl-DWLKAFYDKVAEKLKEAF-amide (Ac-18A-NH(2)) and acetyl
      KWLDAFYDEVAEKLKKAF-amide (Ac-18G*-NH(2)), which differ in charge distribution.
      The fluorescence lifetimes of N-dansyl phosphatidylethanolamine (dansyl-PE) and n
      (9-anthroyloxy)stearic acid (n-AS, n = 2, 6, and 12) were used to assess the
      water penetration into the headgroup and acyl chain regions of
      phosphatidylcholine (PC), respectively. Steady-state fluorescence anisotropy of n
      AS was also performed to evaluate the acyl chain fluidity in emulsion surface
      monolayers. Chol decreased the fluorescence lifetime of dansyl-PE and increased
      the lifetimes and anisotropy values of n-AS. These results demonstrated that Chol
      alters the surface properties of emulsions, i.e., induces PC headgroup separation
      and acyl chain condensation. The two peptides showed different responses to Chol
      in several experiments: Addition of Chol to emulsions decreased and increased the
      dissociation constants of Ac-18A-NH(2) and Ac-18G*-NH(2), respectively.
      Furthermore, the alpha-helical content of Ac-18A-NH(2) was decreased by Chol,
      whereas that of Ac-18G*-NH(2) was unchanged. The higher reduction in helicity for
      Ac-18A-NH(2) is probably due to its deeper penetration than Ac-18G*-NH(2) into
      the hydrocarbon region of surface monolayers in the absence of Chol, which was
      demonstrated by Trp quenching experiments with n-AS. From these results, the
      charge distribution of the amphipathic helices is suggested to be a determining
      factor in their response to Chol enrichment in emulsions.

PMID- 22148177
TI  - Gating NO release from nitric oxide synthase.
AB  - We have investigated the kinetics of NO escape from Geobacillus
      stearothermophilus nitric oxide synthase (gsNOS). Previous work indicated that NO
      release was gated at position 223 in mammalian enzymes; our kinetics experiments
      include mutants at that position along with measurements on the wild type enzyme.
      Employing stopped-flow UV-vis methods, reactions were triggered by mixing a
      reduced enzyme/N-hydroxy-l-arginine complex with an aerated buffer solution. NO
      release kinetics were obtained for wt NOS and three mutants (H134S, I223V,
      H134S/I223V). We have confirmed that wt gsNOS has the lowest NO release rate of
      known NOS enzymes, whether bacterial or mammalian. We also have found that steric
      clashes at positions 223 and 134 hinder NO escape, as judged by enhanced rates in
      the single mutants. The empirical rate of NO release from the gsNOS double mutant
      (H134/I223V) is nearly as rapid as that of the fastest mammalian enzymes,
      demonstrating that both positions 223 and 134 function as gates for escape of the
      product diatomic molecule.

PMID- 22148180
TI  - Biochemical properties of recombinant leucine aminopeptidase II from Bacillus
      stearothermophilus and potential applications in the hydrolysis of Chinese
      anchovy (Engraulis japonicus) proteins.
AB  - The effects of various factors on the activity and conformation of recombinant
      leucine aminopeptidase II (rLAP II) from Bacillus stearothermophilus and its
      potential utilization in the hydrolysis of anchovy proteins were investigated.
      The optimal temperature and pH of rLAP II were 55  degrees C and 8.0 in phosphate
      buffer, and its activity was strongly stimulated by Co(2+). Conformational
      studies indicated that maintaining the alpha-helical structure had a critical
      effect on rLAP II activity. rLAP II was used to hydrolyze anchovy proteins, and
      it exhibited high specificity for peptides with molecular weight between 6000 and
      1000 Da and positive coordination with endogenous enzymes and commercial
      Flavourzyme. Its use will enhance protein hydrolysis in species of aquatic
      animals. rLAP II could potentially be used to remove bitterness in the protein
      hydrolysis industry.

PMID- 22148181
TI  - A combined spectroscopic and computational study of a high-spin S = 7/2 diiron
      complex with a short iron-iron bond.
AB  - The nature of the iron-iron bond in the mixed-valent diiron
      tris(diphenylforamidinate) complex Fe(2)(DPhF)(3), which was first reported by
      Cotton, Murillo et al. (Inorg. Chim. Acta 1994, 219, 7-10), has been examined
      using additional spectroscopic and theoretical methods. It is shown that the
      coupling between the two iron centers is strongly ferromagnetic, giving rise to
      an octet spin ground state. On the basis of Mossbauer spectroscopy, the two iron
      centers, formally mixed-valent Fe(II)Fe(I), are completely equivalent with an
      isomer shift delta = 0.65 mm s(-1) and quadrupole splitting DeltaE(Q) = +0.32 mm
      s(-1). A large, positive zero-field splitting D(7/2) = 8.2 cm(-1) has been
      determined from magnetic susceptibility measurements. Multiconfigurational
      quantum studies of the complete molecule Fe(2)(DPhF)(3) found one dominant
      configuration (sigma)(2)(pi)(4)(pi*)(2)(sigma*)(1)(delta)(2)(delta*)(2), which
      accounts for 73% of the ground-state wave function. By considering all the
      configurations, an estimated metal-metal bond order of 1.15 has been calculated.
      Finally, Fe(2)(DPhF)(3) exhibits weak electronic absorptions in the visible and
      near-infrared regions, which are assigned as d-d transitions from the doubly
      occupied metal-metal pi molecular orbital to half-occupied pi*, delta, and delta*
      orbitals.

PMID- 22148182
TI  - Isotopically modified nanoparticles for enhanced detection in bioaccumulation
      studies.
AB  - This work presents results on synthesis of isotopically enriched (99% (65)Cu)
      copper oxide nanoparticles and its application in ecotoxicological studies.
      (65)CuO nanoparticles were synthesized as spheres (7 nm) and rods (7 * 40 nm).
      Significant differences were observed between the reactivity and dissolution of
      spherical and rod shaped nanoparticles. The extreme sensitivity of the stable
      isotope tracing technique developed in this study allowed determining Cu uptake
      at exposure concentrations equivalent to background Cu concentrations in
      freshwater systems (0.2-30 MUg/L). Without a tracer, detection of newly
      accumulated Cu was impossible, even at exposure concentrations surpassing some of
      the most contaminated water systems (>1 mg/L).

PMID- 22148183
TI  - Access to quinolines through gold-catalyzed intermolecular cycloaddition of 2
      aminoaryl carbonyls and internal alkynes.
AB  - A facile and general method leading to polyfunctionalized quinolines was
      developed. In the presence of a highly efficient combination encompassing
      (PPh)(3)AuCl and AgOTf, the reactions between 2-aminocarbonyls and an array of
      internal alkynes proceeded smoothly to afford quinoline derivatives in good to
      excellent yields (up to 93%).

PMID- 22148185
TI  - Nanostructured bilayered vanadium oxide electrodes for rechargeable sodium-ion
      batteries.
AB  - Tailoring nanoarchitecture of materials offers unprecedented opportunities in
      utilization of their functional properties. Nanostructures of vanadium oxide,
      synthesized by electrochemical deposition, are studied as a cathode material for
      rechargeable Na-ion batteries. Ex situ and in situ synchrotron characterizations
      revealed the presence of an electrochemically responsive bilayered structure with
      adjustable intralayer spacing that accommodates intercalation of Na(+) ions.
      Sodium intake induces organization of overall structure with appearance of both
      long- and short-range order, while deintercalation is accompanied with the loss
      of long-range order, whereas short-range order is preserved. Nanostructured
      electrodes achieve theoretical reversible capacity for Na(2)V(2)O(5) stochiometry
      of 250 mAh/g. The stability evaluation during charge-discharge cycles at room
      temperature revealed an efficient 3 V cathode material with superb performance:
      energy density of ~760 Wh/kg and power density of 1200 W/kg. These results
      demonstrate feasibility of development of the ambient temperature Na-ion
      rechargeable batteries by employment of electrodes with tailored
      nanoarchitectures.

PMID- 22148186
TI  - Functional screening of cytochrome P450 activity and uncoupling by capillary
      electrophoresis.
AB  - Cytochrome P450s (CYPs) are functionally diverse monooxygenases responsible for
      oxidation of endogenous and xenobiotic compounds. The function of nonmammalian
      CYPs are largely unknown and tools for characterization limited. CYPs critical
      for xenobiotic metabolism are prone to catalytic cycle uncoupling resulting in
      reactive oxygen species (ROS) generation that is highly dependent on the specific
      CYP isoform and substrate interaction. This study describes the rapid assessment
      of the activity and coupling efficiency of CYPs using capillary electrophoresis
      with UV detection. The coupling efficiency of five zebrafish (Danio rerio) CYP1
      isoforms with a series of fluorogenic substrate probes was determined by the rate
      of NADP(+) formation and compared with fluorescent product turnover rates. In
      most cases, NADP(+) formation significantly overestimated CYP1 catalytic activity
      for substrate O-dealkylation suggesting uncoupling. ROS production was confirmed
      by elevated hydrogen peroxide generation in poorly coupled reactions. Reactions
      with beta-estradiol confirmed that CYP1A, 1C1, and 1C2 have greater catalytic
      activity and coupling efficiency; CYP1B1 and 1D1 had coupling efficiencies under
      4%. This work highlights the wide disparity in uncoupling induced by unproductive
      substrate binding among different CYP isoforms.

PMID- 22148188
TI  - Synthesis and photophysical properties of biaryl-substituted nucleos(t)ides.
      Polymerase synthesis of DNA probes bearing solvatochromic and pH-sensitive dual
      fluorescent and 19F NMR labels.
AB  - The design of four new fluorinated biaryl fluorescent labels and their attachment
      to nucleosides and nucleoside triphosphates (dNTPs) by the aqueous cross-coupling
      reactions of biarylboronates is reported. The modified dNTPs were good substrates
      for KOD XL polymerase and were enzymatically incorporated into DNA probes. The
      photophysical properties of the biaryl-modified nucleosides, dNTPs, and DNA were
      studied systematically. The different substitution pattern of the biaryls was
      used for tuning of emission maxima in the broad range of 366-565 nm. Using
      methods of computational chemistry the emission maxima were reproduced with a
      satisfactory degree of accuracy, and it was shown that the large solvatochromic
      shifts observed for the studied probes are proportional to the differences in
      dipole moments of the ground (S(0)) and excited (S(1)) states that add on top of
      smaller shifts predicted already for these systems in vacuo. Thus, we present a
      set of compounds that may serve as multipurpose base-discriminating fluorophores
      for sensing of hairpins, deletions, and mismatches by the change of emission
      maxima and intensities of fluorescence and that can be also conviently studied by
      (19)F NMR spectroscopy. In addition, aminobenzoxazolyl-fluorophenyl-labeled
      nucleotides and DNA also exert dual pH-sensitive and solvatochromic fluorescence,
      which may imply diverse applications.

PMID- 22148189
TI  - A multifunctional organic-inorganic hybrid structure based on Mn(III)-porphyrin
      and polyoxometalate as a highly effective dye scavenger and heterogenous
      catalyst.
AB  - A two-step synthesis strategy has led to a unique layered polyoxometalate-Mn(III)
      metalloporphyrin-based hybrid material. The hybrid solid demonstrates remarkable
      capability for scavenging of dyes and for heterogeneous selective oxidation of
      alkylbenzenes with excellent product yields and 100% selectivity.

PMID- 22148190
TI  - Interaction of 5-fluorouracil loaded nanoparticles with 1,2-dimyristoyl-sn
      glycero-3-phosphocholine liposomes used as a cellular membrane model.
AB  - Nuclear magnetic resonance (NMR) spectroscopy and steady-state fluorescence
      anisotropy were used to study the behavior and interaction of 5-fluorouracil,
      both in a free form (5FU) and included in the polymer matrix of
      poly(butylcyanoacrylate) nanoparticles (5FUPBCN) with a phospholipid bilayer of
      large unilammellar vesicles composed of 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC), as a model system of biomembranes. The results confirm an
      interaction and penetration of 5FU into the phospholipid bilayer of DMPC
      liposomes. Different mechanisms of drug transfer from the aqueous environment
      into the model membrane environment, for the free drug and that incorporated into
      polymer nanoparticles, are suggested: (i) concentration-dependent reversible
      diffusion of the free 5FU and (ii) sustained 5FU release from nanoparticles
      adsorbed on the liposome surface resulting in continuous delivery of the drug
      into the phospholipid bilayers of the DMPC liposomes.

PMID- 22148191
TI  - Measurements of the absorption line strength of hydroperoxyl radical in the nu3
      band using a continuous wave quantum cascade laser.
AB  - Mid-infrared absorption spectroscopy has been applied to the detection of the
      hydroperoxyl (HO(2)) radical in pulsed laser photolysis combined with a laser
      absorption kinetics reactor. Transitions of the nu(3) vibrational band assigned
      to the O-O stretch mode were probed with a thermoelectrically cooled, continuous
      wave mid-infrared distributed feedback quantum cascade laser (QCL). The HO(2)
      radicals were generated with the photolysis of Cl(2)/CH(3)OH/O(2) mixtures at 355
      nm. The absorption cross section at each pressure was determined by three methods
      at 1065.203 cm(-1) for the F(1), 13(1,13) <- 14(1,14) transition in the nu(3)
      band. From these values, the absolute absorption cross section at zero pressure
      was estimated. The relative line strengths of other absorptions in the feasible
      emitting frequency range of the QCL from 1061.17 to 1065.28 cm(-1) were also
      measured, and agreed with values reproduced from the HITRAN database. The nu(3)
      band absorption strength was estimated from the analytically obtained absolute
      absorption cross section and the calculated relative intensity by spectrum
      simulation, to be 21.4 +/- 4.2 km mol(-1), which shows an agreement with results
      of quantum chemical calculations.

PMID- 22148193
TI  - Secondary metabolites from the roots of Neolitsea daibuensis and their anti
      inflammatory activity.
AB  - Bioassay-guided fractionation of the roots of Neolitsea daibuensis afforded three
      new beta-carboline alkaloids, daibucarbolines A-C (1-3), three new
      sesquiterpenoids, daibulactones A and B (4 and 5) and daibuoxide (6), and 20
      known compounds. The structures of 1-6 were determined by spectroscopic analysis
      and single-crystal X-ray diffraction. Daibucarboline A (1), isolinderalactone
      (7), 7-O-methylnaringenin (8), and prunetin (9) exhibited moderate iNOS
      inhibitory activity, with IC50 values of 18.41, 0.30, 19.55, and 10.50 MUM,
      respectively.

PMID- 22148194
TI  - Determining the absolute configuration of (+)-mefloquine HCl, the side-effect
      reducing enantiomer of the antimalaria drug Lariam.
AB  - Even though the important antimalaria drug rac-erythro-mefloquine HCl has been on
      the market as Lariam for decades, the absolute configurations of its enantiomers
      have not been determined conclusively. This is needed, since the (-) enantiomer
      is believed to cause adverse side effects in malaria treatment resulting from
      binding to the adenosine receptor in the human brain. Since there are conflicting
      assignments based on enantioselective synthesis and anomalous X-ray diffraction,
      we determined the absolute configuration using a combination of NMR, optical
      rotatory dispersion (ORD), and circular dichroism (CD) spectroscopy together with
      density functional theory calculations. First, structural models of erythro
      mefloquine HCl compatible with NMR-derived (3)J(HH) scalar couplings, (15)N
      chemical shifts, rotational Overhauser effects, and residual dipolar couplings
      were constructed. Second, we calculated ORD and CD spectra of the structural
      models and compared the calculated data with the experimental values. The
      experimental results for (-)-erythro-mefloquine HCl matched our calculated
      chiroptical data for the 11R,12S model. Accordingly, we conclude that the
      assignment of 11R,12S to (-)-erythro-mefloquine HCl is correct.

PMID- 22148195
TI  - Organic pollutant accumulation in vegetation.

PMID- 22148196
TI  - Identification of groundwater solute sources using boron isotopic composition.

PMID- 22148197
TI  - Determination of the efficacy of ozone treatment systems using a gap junction
      intercellular communication bioassay.

PMID- 22148198
TI  - Properties of food grade (edible) surfactants affecting subsurface remediation of
      chlorinated solvents.

PMID- 22148199
TI  - Anaerobic corrosion of granular iron: measurement and interpretation of hydrogen
      evolution rates.

PMID- 22148200
TI  - Electron beam atmospheric pressure cold plasma decomposition of carbon
      tetrachloride and trichloroethylene.

PMID- 22148201
TI  - Bioavailability of naphthalene sorbed to cationic surfactant-modified smectite
      clay.

PMID- 22148203
TI  - Colloid deposition dynamics in flow-through porous media: role of electrolyte
      concentration.

PMID- 22148202
TI  - High accumulation of toxic butyltins in marine mammals from Japanese coastal
      waters.

PMID- 22148204
TI  - Development and Optimization of a TiO2-Coated Fiber-Optic Cable Reactor:
      Photocatalytic Degradation of 4-Chlorophenol.

PMID- 22148205
TI  - Growth and structural change of combustion aerosols at high relative humidity.

PMID- 22148206
TI  - Prometryne oxidation by sodium hypochlorite in aqueous solution: kinetics and
      mechanism.

PMID- 22148208
TI  - Solubility of polychlorinated biphenyls in water/alcohol mixtures. 2. Predictive
      methods.

PMID- 22148207
TI  - Photodegradation of EDTA in the presence of lepidocrocite.

PMID- 22148209
TI  - Chemical oxidation by photolytic decomposition of hydrogen peroxide.

PMID- 22148210
TI  - Micellar solubilization of polynuclear aromatic hydrocarbons in coal tar
      contaminated soils.

PMID- 22148211
TI  - Alternative model for cationic surfactant adsorption by layer silicates.

PMID- 22148212
TI  - Quantification of Individual VOC Reactivity Using a Chemically Detailed, Three
      Dimensional Photochemical Model.

PMID- 22148213
TI  - Biodegradation Kinetics of Highly Chlorinated Biphenyls by Alcaligenes sp. JB1 in
      an Aerobic Continuous Culture System.

PMID- 22148214
TI  - Prediction of partition coefficient and toxicity for phenylthio, phenylsulfinyl
      and phenylsulfonyl acetates.

PMID- 22148215
TI  - Modeling of the proton-metal ion exchange in biosorption.

PMID- 22148216
TI  - Simulation of a Three-Stage Chlorocarbon Incinerator through the Use of a
      Detailed Reaction Mechanism: Chlorine to Hydrogen Mole Ratios below 0.15.

PMID- 22148217
TI  - Comment on "measurement error and spatial variability effects on characterization
      of volatile organics in the subsurface".

PMID- 22148218
TI  - Response to comments on "measurement error and spatial variability effects on
      characterization of volatile organics in the subsurface".

PMID- 22148219
TI  - Comment on "Nickel Adsorption to Hydrous Ferric Oxide in the Presence of EDTA:
      Effects of Component Addition Sequence".

PMID- 22148220
TI  - Response to Comment on "Nickel Adsorption to Hydrous Ferric Oxide in the Presence
      of EDTA: Effects of Component Addition Sequence".

PMID- 22148221
TI  - Comment on "occurrence and distribution of pharmaceutical organic compounds in
      the groundwater downgradient of a landfill (grinsted, denmark)".

PMID- 22148222
TI  - Response to comment on "occurrence and distribution of pharmaceutical organic
      compounds in the groundwater downgradient of a landfill (grinsted, denmark)".

PMID- 22148223
TI  - Comment on "Isomerization of Alkoxy Radicals under Atmospheric Conditions".

PMID- 22148225
TI  - Transport behavior of selected nanoparticles with different surface coatings in
      granular porous media coated with Pseudomonas aeruginosa biofilm.
AB  - Well-controlled laboratory column experiments were conducted to understand the
      influence of Pseudomonas aeruginosa (P. aeruginosa) biofilms on the transport of
      selected engineered nanoparticles (ENPs) in granular porous media representative
      of groundwater aquifers or riverbank filtration settings. To understand the
      importance of particle size on retention in the biofilm-coated granular (quartz
      sand) matrix, column experiments were carried out using nanosized (20 nm) and
      micrometer-sized (1 MUm) sulfate-functionalized polystyrene latex particles
      (designated as 20 nSL and 1 mSL, respectively). Additional experiments conducted
      with nanosized (20 nm) carboxyl-modified latex particles (20nCL) and carboxyl
      modified CdSe/ZnS quantum dots (QDs) provide information on the influence of
      particle surface chemistry on retention. Biofilm grown on the surface of the sand
      was characterized by total biomass quantification, confocal laser scanning
      microscopy (CLSM), and electrokinetic analysis. All four particles exhibit
      increased retention in the biofilm-coated packed bed: e.g., the attachment
      efficiency (alpha) of the 1 mSL particle increases from 0.40 to 1.7, whereas
      alpha for the 20 nSL particle increases from 0.04 to 0.10 in the biofilm-coated
      system. Particle surface chemistry can also influence the affinity of the ENPs
      for the biofilm coating as revealed by the greater attachment of the 20 nSL
      particle onto the biofilm-coated sand (alpha = 0.10) than its carboxylated
      counterpart (alpha = 0.04). Column experiments conducted using sand coated with
      growth medium (LB) or extracellular polymeric substances (EPS) extracted from P.
      aeruginosa biofilms further reveal that particle surface chemistry influences the
      interaction between the different ENPs and these coated sand surfaces. Namely,
      coating of sand surfaces with LB medium or bacterial EPS does not affect the
      transport of the sulfonated nanoparticle, but the LB coating leads to decreased
      retention of the carboxylated latex nanoparticle. Furthermore, our results show
      that EPS coatings are not necessarily good surrogates for biofilm-coated sand.
      Electrokinetic characterization of the clean and coated sand surfaces also
      reveals that the extent of particle retention is not controlled by electrical
      double layer interactions. Future studies should thus be aimed at improving our
      understanding of the fundamental mechanisms (both colloidal and noncolloidal)
      governing nanoparticle transport and fate in biofilm-laden granular aquatic
      environments.

PMID- 22148226
TI  - Anthogorgienes A-O, new guaiazulene-derived terpenoids from a Chinese gorgonian
      Anthogorgia species, and their antifouling and antibiotic activities.
AB  - Fifteen new guaiazulene-based terpenoids designated anthogorgienes A-O (1-15)
      were isolated from a Chinese gorgonian  Anthogorgia  sp., together with eight
      known analogues (16-23). The structural patterns were classified into monomers,
      dimers, and trimers, which were supposed to be generated from a precursor
      guaiazulene and followed by side-chain and nucleus oxidation and oxidative
      rearrangement. The structures of new compounds were elucidated on the basis of
      extensive spectroscopic (IR, MS, and 1D and 2D NMR) data analysis. A possible
      biogenetic relationship of the isolated compounds was postulated. Some of the
      compounds showed potent antifouling activities against the larval settlement of
      barnacle  Balanus amphitrite , whereas their antibiotic activities were also
      evaluated.

PMID- 22148227
TI  - Multiplex sensing of protease and kinase enzyme activity via orthogonal coupling
      of quantum dot-peptide conjugates.
AB  - Nanoparticle-based labels are emerging as simpler and more sensitive alternatives
      to traditional fluorescent small molecules and radioactive reporters in biomarker
      assays. The determination of biomarker levels is a recommended clinical practice
      for the assessment of many diseases, and detection of multiple analytes in a
      single assay, known as multiplexing, can increase predictive accuracy. While
      multiplexed detection can also simplify assay procedures and reduce systematic
      variability, combining multiple assays into a single procedure can lead to
      complications such as substrate cross-reactivity, signal overlap, and loss of
      sensitivity. By combining the specificity of biomolecular interactions with the
      tunability of quantum dot optical properties, we have developed a detection
      system capable of simultaneous evaluation of the activity of two critical enzyme
      classes, proteases and kinases. We avoid cross-reactivity and signal overlap by
      synthesizing enzyme-specific peptide sequences with orthogonal terminal
      functionalization for attachment to quantum dots with distinct emission spectra.
      Enzyme activity is reported via binding of either gold nanoparticle-peptide
      conjugates or FRET acceptor dye-labeled antibodies, which mediate changes in
      quantum dot emission spectra. To the best of our knowledge, this is the first
      demonstration of the multiplexed sensing of the activity of two different classes
      of enzymes via a nanoparticle-based activity assay. Using the quantum dot-based
      assay described herein, we were able to detect the protease activity of urokinase
      type plasminogen activator at concentrations >= 50 ng/mL and the kinase activity
      of human epidermal growth factor receptor 2 at concentrations >= 7.5 nM, levels
      that are clinically relevant for determination of breast cancer prognosis. The
      modular nature of this assay design allows for the detection of different classes
      of enzymes simultaneously and represents a generic platform for high-throughput
      enzyme screening in rapid disease diagnosis and drug discovery.

PMID- 22148228
TI  - Temperature effect on the bilayer stacking in multilamellar lipid vesicles.
AB  - The small-angle region of the Bragg diffraction of MLV samples is a simple and
      powerful tool for the study of mesoscopic lipid structures either alone or in
      interaction with molecules of biological interest. It is also a helpful tool to
      obtain the much needed thermotropic phase diagrams of lipid mixtures. In the
      course of our work, we found that the analysis of the diffractograms obtained as
      a function of temperature is not as straightforward as we expected. When the
      aqueous medium is concentrated in univalent salts, the small-angle X-ray
      scattering, SAXS, develops several peaks that have been interpreted to result
      from regions with different thickness of the interbilayer region. However, a
      systematic study shows that nonzero ionic strength is by no means a necessary
      criterion for irregularity of bilayer stacking. We show that MLV in water are
      uniform and stable if made, kept, and measured at the same temperature. If not,
      the lamellar repeat distance is smaller than the equilibrated one, eventually
      developing transient multimodal SAXS diffractions. We present a detailed study of
      this phenomenon using SAXS and dynamic light scattering and conclude that the
      deviations from the equilibrium interbilayer distance is a consequence of
      geometric constraints created by the insufficient thermal expansion of the lipid
      bilayers.

PMID- 22148229
TI  - Solution-phase mechanistic study and solid-state structure of a tris(bipyridinium
      radical cation) inclusion complex.
AB  - The ability of the diradical dicationic cyclobis(paraquat-p-phenylene)
      (CBPQT(2(*+))) ring to form inclusion complexes with 1,1'-dialkyl-4,4'
      bipyridinium radical cationic (BIPY(*+)) guests has been investigated
      mechanistically and quantitatively. Two BIPY(*+) radical cations, methyl viologen
      (MV(*+)) and a dibutynyl derivative (V(*+)), were investigated as guests for the
      CBPQT(2(*+)) ring. Both guests form trisradical complexes, namely,
      CBPQT(2(*+))?MV(*+) and CBPQT(2(*+))?V(*+), respectively. The structural details
      of the CBPQT(2(*+))?MV(*+) complex, which were ascertained by single-crystal X
      ray crystallography, reveal that MV(*+) is located inside the cavity of the ring
      in a centrosymmetric fashion: the 1:1 complexes pack in continuous radical cation
      stacks. A similar solid-state packing was observed in the case of CBPQT(2(*+)) by
      itself. Quantum mechanical calculations agree well with the superstructure
      revealed by X-ray crystallography for CBPQT(2(*+))?MV(*+) and further suggest an
      electronic asymmetry in the SOMO caused by radical-pairing interactions. The
      electronic asymmetry is maintained in solution. The thermodynamic stability of
      the CBPQT(2(*+))?MV(*+) complex was probed by both isothermal titration
      calorimetry (ITC) and UV/vis spectroscopy, leading to binding constants of (5.0
      +/- 0.6) * 10(4) M(-1) and (7.9 +/- 5.5) * 10(4) M(-1), respectively. The
      kinetics of association and dissociation were determined by stopped-flow
      spectroscopy, yielding a k(f) and k(b) of (2.1 +/- 0.3) * 10(6) M(-1) s(-1) and
      250 +/- 50 s(-1), respectively. The electrochemical mechanistic details were
      studied by variable scan rate cyclic voltammetry (CV), and the experimental data
      were compared digitally with simulated data, modeled on the proposed mechanism
      using the thermodynamic and kinetic parameters obtained from ITC, UV/vis, and
      stopped-flow spectroscopy. In particular, the electrochemical mechanism of
      association/dissociation involves a bisradical tetracationic intermediate
      CBPQT((2+)(*+))?V(*+) inclusion complex; in the case of the V(*+) guest, the rate
      of disassociation (k(b) = 10 +/- 2 s(-1)) was slow enough that it could be
      detected and quantified by variable scan rate CV. All the experimental
      observations lead to the speculation that the CBPQT((2+)(*+)) ring of the
      bisradical tetracation complex might possess the unique property of being able to
      recognize both BIPY(*+) radical cation and pi-electron-rich guests
      simultaneously. The findings reported herein lay the foundation for future
      studies where this radical-radical recognition motif is harnessed particularly in
      the context of mechanically interlocked molecules and increases our fundamental
      understanding of BIPY(*+) radical-radical interactions in solution as well as in
      the solid-state.

PMID- 22148233
TI  - Lumutinines A-D, linearly fused macroline-macroline and macroline-sarpagine
      bisindoles from Alstonia macrophylla.
AB  - Four new linearly fused bisindole alkaloids, lumutinines A-D (1-4), were isolated
      from the stem-bark extract of Alstonia macrophylla. Lumutinines A (1) and B (2)
      represent the first examples of linear, ring A/F-fused macroline-macroline-type
      bisindoles, while lumutinines C (3) and D (4) were constituted from the union of
      macroline and sarpagine moieties. A reinvestigation of the stereochemical
      assignment of alstoumerine (8) by NMR and X-ray diffraction analyses indicated
      that the configuration at C-16 and C-19 required revision.

PMID- 22148232
TI  - Probing biomolecular interactions with dual polarization interferometry: real
      time and label-free coralyne detection by use of homoadenine DNA oligonucleotide.
AB  - We incorporated the specific recognition of adenine-rich singled-stranded DNA
      (ssDNA) into dual polarization interferometry (DPI) measurements for direct,
      selective, and sensitive detection of the small molecule coralyne, and we
      simultaneously employed the real-time and label-free technique for detailed
      investigation of the interaction between coralyne and adenine-rich ssDNA. Data
      from UV-visible spectroscopy, circular dichroism (CD) spectroscopy, and DNA
      melting firmly confirmed that 48-mer homoadenine ssDNA oligonucleotide (A(48))
      had highly specific recognition for coralyne, whereas 48-mer homothymine ssDNA
      oligonucleotide (T(48)) as the control had no such recognition. The
      immobilization of ssDNA (A(48) or T(48)) on a silicon oxynitride chip could be
      achieved through a preadsorbed poly(ethylenimine) (PEI) layer. Mass, thickness,
      and refractive index (RI) changes resolved by DPI during the whole process of
      ssDNA immobilization suggested that most ssDNA molecules were likely to lie on
      the PEI surface mainly in the form of a flat monolayer and insert themselves
      partly into the PEI layer. Qualitative and quantitative analysis of mass,
      thickness, and RI changes in A(48)/PEI layer upon addition of different
      concentrations of coralyne revealed that A(48) most likely underwent a
      conformational change from single-stranded to double-stranded structure. By
      evaluation of the binding curves from changes in mass, the association rate
      constant (k(a)), dissociation rate constant (k(d)), and association constant
      (K(A)) between coralyne and A(48) were determined to be 4.95 * 10(3) M(-1) s(-1),
      0.031 s(-1), and 1.6 * 10(5) M(-1), respectively. Good linear correlations
      between coralyne concentrations ranging from 0.5 to 12 MUM and three parameters
      (mass, thickness, and RI) resolved by the response to coralyne binding were
      obtained. The detection limits were 0.22 MUM for mass calibration, 0.14 MUM for
      thickness calibration, and 0.32 MUM for RI calibration. The high selectivity of
      the biosensor to coralyne at the A(48)/PEI interface was successfully confirmed
      by using the other two interfaces (T(48)/PEI and PEI) and three typical
      intercalators (ethidium bromide, daunomycin, and methylene blue). It is expected
      that the biosensing platform may be extended to simultaneously detect and
      characterize the interactions of a variety of target molecules with functional
      DNA molecules with high sensitivity.

PMID- 22148234
TI  - Aggregation of donor base stabilized 2-thienyllithium in a single crystal and in
      solution: distances from X-ray diffraction and the nuclear Overhauser effect.
AB  - Various 2-thienyllithium derivatives were investigated in the solid state by X
      ray diffraction and in solution by 2D NMR experiments. The determined structures
      of [(Et(2)O)Li(C(4)H(3)S)](4) (1), [(THF)(2)Li(C(4)H(3)S)](2) (2),
      [(DME)Li(C(4)H(3)S)](2) (3), [(TMEDA)Li(C(4)H(3)S)](2) (4), and
      [(PMDETA)Li(C(4)H(3)S)] (5) (DME = 1,2-dimethoxyethane, TMEDA = N,N,N',N'
      tetramethylethylene-1,2-diamine, and PMDETA = N,N,N',N",N"
      pentamethyldiethylenetriamine) were solved in nondonating toluene and provide
      firm ground for diffusion-ordered NMR spectroscopy as well as heteronuclear
      Overhauser enhancement NMR spectroscopy. The distance relation of nuclear
      Overhauser effects with a factor of r(-6) is employed to gain further insight
      into the aggregation degree of 1-5 in solution. Comparison of the slope provided
      by the linear region of the buildup curves and of the ?r(-6) calculated distances
      from the crystal structures offers a handle to judge the structure retention
      versus conversion in solution. The structures of 3-5 are maintained in toluene
      solution. The data of 2, however, indicate a partial dissociation or a rapid
      exchange between the vertices of a tetrameric core and free THF molecules.
      Auxiliary exchange spectroscopy investigations showed that the signals of the
      nitrogen donor base containing compounds 4 and 5 exchange with the signals of
      nonlithiated thiophene. This is explained by exchange of the deuterium by a
      hydrogen atom via lithiation of toluene molecules.

PMID- 22148235
TI  - Insights from chiral polyfluorene on the unification of molecular exciton and
      cholesteric liquid crystal theories for chiroptical phenomena.
AB  - The Maugin-Oseen-DeVries theory accounts for chiroptical properties of
      cholesteric films with long-range order. For molecular systems with short-range
      structural correlation lengths, molecular exciton theory is used. A consistent
      description for systems with intermediate correlation lengths is lacking. Films
      of chiral polyfluorene behave according to Maugin-Oseen-DeVries theory when the
      film thickness exceeds 300 nm. Properties of thin films are consistent with
      molecular exciton theory. We describe the crossover in the optical properties of
      the film in a phenomenological way using a dielectric tensor that contains terms
      from Maugin-Oseen-DeVries and molecular exciton theory. Guided by the
      experimental findings, we explore the possibility of a unification of the Maugin
      Oseen-DeVries and molecular exciton theory involving a coupled oscillator model.

PMID- 22148236
TI  - 4',5'-Dichloro-2',7'-dimethoxy-5(6)-carboxyfluorescein (JOE): synthesis and
      spectral properties of oligonucleotide conjugates.
AB  - A convenient procedure for the preparation of the fluorescent dye 4',5'-dichloro
      2',7'-dimethoxy-5(6)-carboxyfluorescein (JOE) is reported; the overall yield
      achieved starting from isovanillin is 10 times higher (40% vs 4%) compared to the
      known procedure. Isomers (5- and 6-) are easily chromatographically separable as
      pentafluorophenyl esters of 3',6'-O-bis(cyclohexylcarbonyl) derivatives. Four non
      nucleoside JOE phosphoramidites based on 5- and 6-isomers and flexible 6
      aminohexanol (AH) or rigid 4-trans-aminocyclohexanol (ACH) linkers have been
      prepared and used for oligonucleotide labeling. Spectral and photophysical
      properties of 5'-JOE-modified oligonucleotides have been studied. Fluorescence
      quantum yield of the dye correlates with the nature of the linker (rigid vs
      flexible) and with the presence of dG nucleosides in close proximity to a JOE
      residue.

PMID- 22148239
TI  - Enantiomeric resolution and growth-retardant activity in rice seedlings of
      uniconazole.
AB  - The increasing application of chiral pesticides has enhanced interest in their
      enantioselectivity. However, little relevant information is currently available
      for enantioselective activity of chiral plant growth regulators. In an attempt to
      screen active enantiomers of uniconazole, this work investigated enantiomeric
      separation and the enantioselective effect of uniconazole on the growth of rice
      seedlings and cyanobacteria. Baseline resolution of uniconazole enantiomers was
      achieved on a Chiralpak AD column by chiral high-performance liquid
      chromatography (HPLC). The relationship among circular dichroism (CD), optical
      rotation (OR), and absolute configuration was successfully established by
      coupling of CD and OR detection. The t test at the 95% level of confidence
      indicated significant differences between the enantiomers in their retardant
      activity toward growth of rice seedlings and stimulation effect on growth of
      cyanobacteria, the natural biofertilizers in rice paddy fields. The S-(+)
      enantiomer was more active than the R-(-)-enantiomer in retarding growth of rice
      seedlings and stimulating growth of  Microcystis aeruginosa . This special
      enantiomeric selectivity was further elucidated by probing the binding mode of
      enantiomers to gibberellin (GA) 20-oxidase by molecular docking. The S-(+)
      enantiomer was found to bind tightly with GA 20-oxidase. The results suggested
      that the S-(+)-enantiomer instead of a racemate of uniconazole should be used to
      improve rice seedling quality.

PMID- 22148238
TI  - Mechanism of silver nanoparticle toxicity is dependent on dissolved silver and
      surface coating in Caenorhabditis elegans.
AB  - The rapidly increasing use of silver nanoparticles (Ag NPs) in consumer products
      and medical applications has raised ecological and human health concerns. A key
      question for addressing these concerns is whether Ag NP toxicity is
      mechanistically unique to nanoparticulate silver, or if it is a result of the
      release of silver ions. Furthermore, since Ag NPs are produced in a large variety
      of monomer sizes and coatings, and since their physicochemical behavior depends
      on the media composition, it is important to understand how these variables
      modulate toxicity. We found that a lower ionic strength medium resulted in
      greater toxicity (measured as growth inhibition) of all tested Ag NPs to
      Caenorhabditis elegans and that both dissolved silver and coating influenced Ag
      NP toxicity. We found a linear correlation between Ag NP toxicity and dissolved
      silver, but no correlation between size and toxicity. We used three independent
      and complementary approaches to investigate the mechanisms of toxicity of
      differentially coated and sized Ag NPs: pharmacological (rescue with trolox and N
      acetylcysteine), genetic (analysis of metal-sensitive and oxidative stress
      sensitive mutants), and physicochemical (including analysis of dissolution of Ag
      NPs). Oxidative dissolution was limited in our experimental conditions (maximally
      15% in 24 h) yet was key to the toxicity of most Ag NPs, highlighting a critical
      role for dissolved silver complexed with thiols in the toxicity of all tested Ag
      NPs. Some Ag NPs (typically less soluble due to size or coating) also acted via
      oxidative stress, an effect specific to nanoparticulate silver. However, in no
      case studied here was the toxicity of a Ag NP greater than would be predicted by
      complete dissolution of the same mass of silver as silver ions.

PMID- 22148240
TI  - Photoassisted magnetization of fullerene C60 with magnetic-field trapped Raman
      scattering.
AB  - We report a photoassisted method to magnetize microcrystal fullerene C(60) at
      room temperature by exciting it to triplet states via a proper laser radiation
      and then trapping the spin-polarized states under a strong magnetic field. Novel
      changes on Raman scattering of the C(60) microcrystals were observed in the
      presence and absence of the magnetic field. In particular, the Raman spectra were
      found to exhibit a "hysteresis" phenomenon when the external magnetic field was
      removed. In light of this, we propose magnetic-field-trapped Raman spectroscopy
      (MFTRS) and employ first-principle calculations to reproduce the Raman activities
      of C(60) at different states. Further, MFTRS of the fullerene is demonstrated to
      originate from its photoassisted magnetization (PAM). The PAM strategy enables
      the magnetization of materials which consist of only light elements; meanwhile,
      the MFTRS investigation may open a new research field in Raman spectroscopy.

PMID- 22148241
TI  - Cyclopeptide Alkaloids from Ziziphus apetala.
AB  - Six novel Ia3-type cyclopeptide alkaloids (1-6) were isolated from stems of
      Ziziphus apetala. Compound 5 and the known compounds mauritine A (7) and
      mauritine F (8) were isolated from the roots. Their structures were determined by
      spectroscopic analyses and chemical methods. The total alkaloids from the roots
      and the isolated cyclopeptide alkaloids were tested for antidepressant behavior
      on mice, cytotoxicity, and 11beta-hydroxysteroid dehydrogenase (11beta-HSD)
      inhibition in vitro. Only mauritine A (7) showed inhibitory activity on 11beta
      HSD1, with IC50 values of 52.0 (human) and 31.2 MUg/mL (mouse).

PMID- 22148242
TI  - Experimental and theoretical enthalpies of formation of glycine-based
      sulfate/bisulfate amino acid ionic liquids.
AB  - The experimental and theoretical enthalpies of formation of several structural
      similar glycine-based sulfate/bisulfate amino acid ionic liquids including
      glycine sulfate (Gly(2)SO(4), 1), glycine bisulfate (GlyHSO(4), 2), N,N
      dimethylglycine sulfate ([DMGly](2)SO(4), 3), N,N-dimethylglycine bisulfate
      ([DMGly]HSO(4), 4), N,N-dimethylglycine methyl ester sulfate
      ([DMGlyC(1)](2)SO(4), 5), N,N-dimethylglycine methyl ester bisulfate
      ([DMGlyC(1)]HSO(4), 6), N,N,N-trimethylglycine methyl ester sulfate
      ([TMGlyC(1)](2)SO(4), 7), and N,N,N-trimethylglycine methyl ester bisulfate
      ([TMGlyC(1)]HSO(4), 8) were studied. Their experimental enthalpies of formation
      were obtained from the corresponding energies of combustion determined by the
      bomb calorimetry method. The enthalpies of formation of these amino acid ionic
      liquids are in the range from -1406 kJ mol(-1) to -1128 kJ mol(-1). Systematic
      theoretical study on these amino acid ionic liquids were performed by quantum
      chemistry calculation using the Gaussian03 suite of programs. The geometric
      optimization and the frequency analyses are carried out using the B3LYP method
      with the 6-31+G** basis set. Their calculated enthalpies of formation were
      derived from the single point energies carried out with the HF/6-31+G**, B3LYP/6
      31+G**, B3LYP/6-311++G**, and MP2/6-311++G** level of theory, respectively. The
      relevance of experimental and calculated enthalpies of formation was studied. The
      calculated enthalpies of formation are in good agreement with their experimental
      data in less than 3% error.

PMID- 22148244
TI  - Photolysis (193 nm) of SO2: nascent product energy distribution examined through
      IR emission.
AB  - Infrared emission following the photolysis of SO(2) by a 193 nm laser pulse (20
      ns duration) was recorded with 500 ns time and 10 cm(-1) spectral resolution.
      Spectral analyses of the time-resolved spectra revealed the vibrationally excited
      nascent SO population distribution as (v = 1)/(v = 2)/(v = 3)/(v = 4)/(v = 5) =
      0.54 +/- 0.04, 1.00 +/- 0.03, 0.00 +/- 0.03, 0.01 +/- 0.03, and 0.10 +/- 0.03.
      The nascent SO was found to be rotationally excited with an average rotational
      temperature around 1000 K for v = 1 and v = 2 levels and 300 K for the v = 5
      level. The vibrationally excited SO likely originates from two distinct
      dissociation mechanisms; the v = 1 and 2 populations are generated through
      intersystem crossing between the C state and a repulsive state (2(3)A'), and the
      v = 5 population is generated through internal conversion from the C to the X
      state. Efficient V-V energy transfer from nascent vibrationally excited SO to
      SO(2)(nu(1)) is also observed. The appearance of the SO(2)(nu(1)) nu(1) = 2
      emission, before that from the nu(1) = 1 population is consistent with the
      previous report that the Deltanu = -2 channel is more efficient than the Deltanu
      = -1 channel.

PMID- 22148245
TI  - Statistical total correlation spectroscopy scaling for enhancement of metabolic
      information recovery in biological NMR spectra.
AB  - The high level of complexity in nuclear magnetic resonance (NMR) metabolic
      spectroscopic data sets has fueled the development of experimental and
      mathematical techniques that enhance latent biomarker recovery and improve model
      interpretability. We previously showed that statistical total correlation
      spectroscopy (STOCSY) can be used to edit NMR spectra to remove drug metabolite
      signatures that obscure metabolic variation of diagnostic interest. Here, we
      extend this "STOCSY editing" concept to a generalized scaling procedure for NMR
      data that enhances recovery of latent biochemical information and improves
      biological classification and interpretation. We call this new procedure STOCSY
      scaling (STOCSY(S)). STOCSY(S) exploits the fixed proportionality in a set of NMR
      spectra between resonances from the same molecule to suppress or enhance features
      correlated with a resonance of interest. We demonstrate this new approach using
      two exemplar data sets: (a) a streptozotocin rat model (n = 30) of type 1
      diabetes and (b) a human epidemiological study utilizing plasma NMR spectra of
      patients with metabolic syndrome (n = 67). In both cases significant biomarker
      discovery improvement was observed by using STOCSY(S): the approach successfully
      suppressed interfering NMR signals from glucose and lactate that otherwise
      dominate the variation in the streptozotocin study, which then allowed recovery
      of biomarkers such as glycine, which were otherwise obscured. In the metabolic
      syndrome study, we used STOCSY(S) to enhance variation from the high-density
      lipoprotein cholesterol peak, improving the prediction of individuals with
      metabolic syndrome from controls in orthogonal projections to latent structures
      discriminant analysis models and facilitating the biological interpretation of
      the results. Thus, STOCSY(S) is a versatile technique that is applicable in any
      situation in which variation, either biological or otherwise, dominates a data
      set at the expense of more interesting or important features. This approach is
      generally appropriate for many types of NMR-based complex mixture analyses and
      hence for wider applications in bioanalytical science.

PMID- 22148246
TI  - Heteroepitaxial streptavidin nanocrystals reveal critical role of proton
      "fingers" and subsurface atoms in determining adsorbed protein orientation.
AB  - Characterization of noncovalent interactions between nanometer-sized structures,
      such as proteins, and solid surfaces is a subject of intense interest of late
      owing to the rapid development of numerous solid materials for medical and
      technological applications. Yet the rational design of these surfaces to promote
      the adsorption of specific nanoscale complexes is hindered by a lack of an
      understanding of the noncovalent interactions between nanostructures and solid
      surfaces. Here we take advantage of the unexpected observation of two-dimensional
      nanocrystals of streptavidin on muscovite mica to provide details of the
      streptavidin-mica interface. Analysis of atomic force microscopic images together
      with structural modeling identifies six positively charged residues whose
      terminal amine locations match the positions of the single atom-sized anionic
      cavities in the basal mica surface to within 1 A. Moreover, we find that the
      streptavidin crystallites are oriented only along a single direction on this
      surface and not in either of three different directions as they must be if the
      protein interacted solely with the 3-fold symmetric basal surface atoms. Hence,
      this broken symmetry indicates that the terminal amine protons must also interact
      directly with the subsurface hydroxide atoms that line the bottom of these
      anionic cavities and generate only a single axis of symmetry. Thus, in total,
      these results reveal that subsurface atoms can have a significant influence on
      protein adsorption and orientation and identify the insertion of proton "fingers"
      as a means by which proteins may generally interact with solid surfaces.

PMID- 22148247
TI  - Synthetic and quantum mechanical studies into the N-heterocyclic carbene
      catalyzed (4 + 2) cycloaddition.
AB  - The N-heterocyclic carbene catalyzed (4 + 2) cycloaddition between alpha,beta
      unsaturated acid fluorides and TMS dienol ethers provides cyclohexene fused beta
      lactone intermediates stable below -20  degrees C. These can be intercepted
      reductively or with organolithium reagents to produce diastereomerically pure
      cyclohexenes (>20:1 dr) with up to four contiguous stereocenters. The mechanism
      has been investigated using theoretical calculations and by examining secondary
      kinetic isotope effects. Together these studies implicate the formation of a
      diastereomerically pure beta-lactone intermediate by a stepwise (4 + 2)
      cycloaddition involving Michael addition, aldol cyclization, and lactonization.

PMID- 22148249
TI  - Formation dynamics of excitons and temporal behaviors of Fano resonance due to
      the exciton-impurity-phonon configuration interaction in ZnO.
AB  - Formation dynamics of free and neutral donor bound excitons (FX and D(0)X) in a
      high quality ZnO single crystal are studied by means of time-resolved
      photoluminescence (TRPL) at various temperatures. At low-temperatures, FX and
      D(0)X formation times are determined to be ~5 and ~10 ps, respectively, by
      fitting the rise process with the Boltzmann sigmoidal function. Temporal
      information of FX- and D(0)X-longitudinal optical (LO) phonon coupling is also
      acquired by measuring TRPL spectra of the first-order LO phonon-assisted FX and
      D(0)X transitions. In particular, interesting time evolution of luminescence
      intensity in the Fano resonance region due to the configuration interaction of
      exciton-impurity-phonon is explored.

PMID- 22148250
TI  - Extension of Marcus picture for electron transfer reactions with large solvation
      changes.
AB  - The standard Marcus theory of charge transfer reaction in solution, relying on a
      Gaussian solvation picture, or, equivalently, on a linear response approximation,
      and involving two parameters, the reorganization energy and the reaction free
      energy parameter, may fail when the solvation has a different character in the
      reactant and product state. We propose two complementary theoretical extensions
      of Marcus theory applying to those cases, based either on a two-Gaussian-states
      solvation picture, or on a non-Gaussian solvation picture. As illustration, we
      show that such situations arise even for simple half oxido-reduction reactions
      involving the Cu(+)/Cu(2+) or Ag(0)/Ag(+) couples, for which electron transfer
      free-energy surfaces have been generated using first-principle molecular dynamics
      simulations. The two theoretical extensions are shown to exhibit the correct
      nonlinear response behavior and to reproduce the simulation results
      quantitatively, whereas a simple one-Gaussian-state Marcus description breaks
      down.

PMID- 22148251
TI  - Using 17O to investigate nitrate sources and sinks in a semi-arid groundwater
      system.
AB  - We apply a triple isotope approach for nitrate that utilizes Delta(17)O as a
      conservative tracer, in combination with delta(18)O and delta(15)N, to assess
      source/sink dynamics of groundwater nitrate beneath alluvial washes in a semiarid
      urban setting. Other studies have used delta(18)O and delta(15)N to determine
      nitrate sources and cycling, but the atmospheric delta(18)O signature can be
      overprinted by biogeochemical processes. In this study, delta(18)O and delta(15)N
      values of nitrate were coupled with delta(17)O values of nitrate to quantify
      atmospheric nitrate inputs and denitrification amounts. Results show generally
      low groundwater nitrate concentrations (<0.2 mmol/L) throughout the basin; high
      nitrate concentrations (up to 1 mmol/L) with evidence for some denitrification
      were detected in areas where effluent was the predominant source of recharge to
      groundwater. Furthermore, the denitrification was inferred from elevated
      delta(18)O and delta(15)N values which were reinforced by increases in observed
      delta(17)O values. Finally, relatively low, but significant atmospheric nitrate
      concentrations were measured in groundwater (up to 6% of total nitrate). This
      study concludes that the triple isotope approach improves determination of the
      proportion of atmospheric nitrate and the significance of denitrification in
      natural waters, allowing us to develop a conceptual model of the biogeochemical
      processes controlling nitrogen in an urban setting.

PMID- 22148254
TI  - Ruthenium complex containing block copolymer for the enhancement of carbon
      nanotube photoconductivity.
AB  - We report the synthesis of a multifunctional block copolymer incorporated with
      pyrene and ruthenium terpyridyl thiocyanato complex moieties by reversible
      addition-fragmentation chain transfer polymerization. The pyrene block in the
      copolymer facilitates the dispersion of multiwalled carbon nanotubes in DMF
      solution because of the strong pi-pi interaction between the pyrene moieties and
      nanotube surface. On the other hand, the ruthenium complexes greatly enhance the
      photosensitivity of the functionalized nanotubes in the visible region. The
      photocurrent responses of the nanotubes at different wavelength measured by
      conductive AFM spectrum strongly agree with the absorption spectrum of the
      ruthenium complex. The results demonstrate a new and versatile approach in
      enhancing and fine-tuning the photosensitivity or other opto-electronic
      properties of carbon nanotubes by multifunctional block copolymers.

PMID- 22148253
TI  - Nitric oxide release is not required to decrease the ulcerogenic profile of
      nonsteroidal anti-inflammatory drugs.
AB  - The objective of this work was to evaluate the biological properties of a new
      series of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs)
      possessing a tyrosol linker between the NSAID and the NO-releasing moiety
      (PROLI/NO); however, initial screening of ester intermediates without the
      PROLI/NO group showed the required (desirable) efficacy/safety ratio, which
      questioned the need for NO in the design. In this regard, NSAID ester
      intermediates were potent and selective COX-2 inhibitors in vitro, showed
      equipotent anti-inflammatory activity compared to the corresponding parent NSAID,
      but showed a markedly reduced gastric toxicity when administered orally. These
      results provide complementary evidence to challenge the currently accepted notion
      that hybrid NO-NSAIDs exert their cytoprotective effects by releasing NO. Results
      obtained in this work constitute a good body of evidence to initiate a debate
      about the future replacement of NSAID prodrugs for unprotected NSAIDs (possessing
      a free carboxylic acid group) currently in clinical use.

PMID- 22148255
TI  - Oxalic acid supported Si-18F-radiofluorination: one-step radiosynthesis of N
      succinimidyl 3-(di-tert-butyl[18F]fluorosilyl)benzoate ([18F]SiFB) for protein
      labeling.
AB  - N-Succinimidyl 3-(di-tert-butyl[(18)F]fluorosilyl)benzoate ([(18)F]SiFB), a novel
      synthon for one-step labeling of proteins, was synthesized via a simple (18)F
      (19)F isotopic exchange. A new labeling technique that circumvents the cleavage
      of the highly reactive active ester moiety under regular basic (18)F-labeling
      conditions was established. In order to synthesize high radioactivity amounts of
      [(18)F]SiFB, it was crucial to partially neutralize the potassium
      oxalate/hydroxide that was used to elute (18)F(-) from the QMA cartridge with
      oxalic acid to prevent decomposition of the active ester moiety. Purification of
      [(18)F]SiFB was performed by simple solid-phase extraction, which avoided time
      consuming HPLC and yielded high specific activities of at least 525 Ci/mmol and
      radiochemical yields of 40-56%. In addition to conventional azeotropic drying of
      (18)F(-) in the presence of [K(+)?2.2.2.]C(2)O(4), a strong anion-exchange (SAX)
      cartridge was used to prepare anhydrous (18)F(-) for nucleophilic radio
      fluorination omitting the vacuum assisted drying of (18)F(-). Using a lyophilized
      mixture of [K(+)?2.2.2.]OH resolubilized in acetonitrile, the (18)F(-) was eluted
      from the SAX cartridge and used directly for the [(18)F]SiFB synthesis.
      [(18)F]SiFB was applied to the labeling of various proteins in likeness to the
      most commonly used labeling synthon in protein labeling, N-succinimidyl-4
      [(18)F]fluorobenzoate ([(18)F]SFB). Rat serum albumin (RSA), apo-transferrin, a
      beta-cell-specific single chain antibody, and erythropoietin were successfully
      labeled with [(18)F]SiFB in good radiochemical yields between 19% and 36%.
      [(18)F]SiFB- and [(18)F]SFB-derivatized RSA were directly compared as blood pool
      imaging agents in healthy rats using small animal positron emission tomography.
      Both compounds demonstrated identical biodistributions in healthy rats,
      accurately visualizing the blood pool with PET.

PMID- 22148257
TI  - Stability of citral in emulsions coated with cationic biopolymer layers.
AB  - Multilayer emulsions containing citral were prepared by the layer-by-layer
      deposition technique based on the electrostatic interaction between negatively
      charged emulsion droplets and two positively charged biopolymer coatings,
      chitosan (CS) and epsilon-polylysine (EPL). The optimum concentrations of both CS
      and EPL were determined through the zeta-potential and particle size measurements
      and were found to be 1.5 mg/mL for CS and 6 mg/mL for EPL. Quartz crystal
      microbalance with dissipation monitoring (QCM-D) was conducted to monitor the
      binding between emulsion droplets and cationic polymers, and our results proved
      the existence of strong interactions between emulsions and the cationic polymer
      coatings. The stability of citral and the production of the off-flavor compounds
      were analyzed by solid-phase microextraction gas chromatography (SPME-GC). The
      results suggested that the addition of the cationic CS interfacial layer was
      effective in improving the stability of citral during storage.

PMID- 22148258
TI  - Biologically active polymersomes from amphiphilic glycopeptides.
AB  - Polypeptide block copolymers with different block length ratios were obtained by
      sequential ring-opening polymerization of benzyl-L-glutamate and propargylglycine
      (PG) N-carboxyanhydrides. Glycosylation of the poly(PG) block was obtained by
      Huisgens cycloaddition "click" reaction using azide-functionalized galactose. All
      copolymers were self-assembled using the nanoprecipitation method to obtain
      spherical and wormlike micelles as well as polymersomes depending on the block
      length ratio and the nanoprecipitation conditions. These structures display
      bioactive galactose units in the polymersome shell, as proven by selective lectin
      binding experiments.

PMID- 22148259
TI  - Resonance quenching and guided modes arising from the coupling of surface
      plasmons with a molecular resonance.
AB  - In this paper, we describe experimental and modeling results that illucidate the
      nature of coupling between surface plasmon polaritons in a thin silver film with
      the molecular resonance of a zinc phthalocyanine dye film. This coupling leads to
      several phenomena not generally observed when plasmons are coupled to transparent
      materials. The increased absorption coefficient near a molecular resonance leads
      to a discontinuity in the refractive index, which causes branching of the plasmon
      resonance condition and the appearance of two peaks in the p-polarized
      reflectance spectrum. A gap exists between these peaks in the region of the
      spectrum associated with the molecular resonance and reflects quenching of the
      plasmon wave due to violation of the resonance condition. A second observation is
      the appearance of a peak in the s-polarized reflection spectra. The initial
      position of this peak corresponds to where the refractive index of the adsorbate
      achieves its largest value, which occurs at wavelengths just slightly larger than
      the maximum in the molecular resonance. Although this peak initially appears to
      be nondispersive, both experimental data and optical modeling indicate that
      increasing the film thickness shifts the peak position to longer wavelengths,
      which implies that this peak is not associated with the molecular resonance but,
      rather, is dispersive in nature. Indeed, modeling shows that this peak is due to
      a guided mode in the film, which appears in these conditions due to the
      abnormally high refractive index of the film near the absorbance maximum. Results
      also show that, with increasing film thickness, numerous additional guided modes
      appear and move throughout the visible spectrum for both s- and p-polarized
      light. Notably, these guided modes are also quenched near the location of the
      molecular resonance. The quenching of both the plasmon resonance and the guided
      modes can be explained by a large decrease in the in-plane wave propagation
      length that occurs near the molecular resonance, which is a direct result of the
      film's large absorption coefficient.

PMID- 22148262
TI  - Modeling the behavior of coarse-grained polymer chains in charged water droplets:
      implications for the mechanism of electrospray ionization.
AB  - The mechanism whereby macromolecular analytes are transferred into the gas phase
      during the final stages of electrospray ionization (ESI) remains a matter of
      debate. In this work, we employ molecular dynamics simulations to examine the
      temporal behavior of nanometer-sized aqueous ESI droplets containing a polymer
      chain and excess ammonium ions. The polymer is modeled using a coarse-grained
      framework where a bead-string backbone is decorated with side chains that can be
      nonpolar, cationic, or anionic. Polymers that adopt compact conformations and
      that carry a large number of charged side chains remain close to the droplet
      center, where the charges are extensively hydrated. The ESI process for these
      compact/hydrophilic macromolecules must involve solvent evaporation to dryness.
      This behavior is consistent with the charged residue model (CRM). A completely
      different scenario is encountered for disordered (extended) chains that carry a
      large number of nonpolar side chains. In this case, the macromolecule tends to be
      rapidly expelled from the droplet surface in a stepwise sequential fashion. This
      process produces metastable structures where one end of the extended polymer
      chain remains connected with the droplet via charge solvation. Disruption of
      these last interactions will then produce a free gas phase macromolecular ion.
      The data of this work imply that the ESI process for unfolded/hydrophobic
      polymers proceeds via an ion evaporation (IEM)-like mechanism that is facilitated
      by hydrophobic solute/solvent interactions. Our model predicts that the ESI
      efficiency of the latter scenario is considerably higher than for the CRM. This
      prediction is verified experimentally through ESI mass spectrometry measurements
      on myoglobin.

PMID- 22148260
TI  - Induction of apoptosis by 3-amino-6-(3-aminopropyl)-5,6-dihydro-5,11-dioxo-11H
      indeno[1,2-c]isoquinoline via modulation of MAPKs (p38 and c-Jun N-terminal
      kinase) and c-Myc in HL-60 human leukemia cells.
AB  - Recently, we reported that 3-amino-6-(3-aminopropyl)-5,6-dihydro-5,11-dioxo-11H
      indeno[1,2-c]isoquinoline (AM6-36), sharing structural similarity with naturally
      occurring isoquinolines, induced activities mediated by retinoid X receptor (RXR)
      response element accompanied by antiproliferative effects on breast cancer cells.
      To further characterize the biologic potential of AM6-36, we currently report
      studies conducted with HL-60 human leukemia cells. AM6-36 significantly inhibited
      cellular proliferation in a dose- and time-dependent manner with an IC(50) value
      of 86 nM. When evaluated at low test concentrations (<=0.25 MUM), AM6-36 induced
      arrest in the G2/M phase of the cell cycle. At higher concentrations (1 and 2
      MUM), the response shifted to apoptosis, which was consistent with the effect of
      AM6-36 on other apoptotic signatures including an increase of apoptotic annexin
      V(+) 7-AAD(-) cells, loss of mitochondrial membrane potential, induction of
      poly(ADP-ribose) polymerase cleavage, and activation of several caspases. These
      apoptotic effects are potentially due to up-regulation of p38 MAPK and JNK
      phosphorylation and down-regulation of c-Myc oncogene expression. Taken together,
      AM6-36 might serve as an effective anticancer agent by inducing G2/M cell cycle
      arrest and apoptosis through the activation of MAPKs and inhibition of c-Myc.

PMID- 22148263
TI  - Indium-mediated asymmetric Barbier-type propargylations: additions to aldehydes
      and ketones and mechanistic investigation of the organoindium reagents.
AB  - We report a simple, efficient, and general method for the indium-mediated
      enantioselective propargylation of aromatic and aliphatic aldehydes under Barbier
      type conditions in a one-pot synthesis affording the corresponding chiral alcohol
      products in very good yield (up to 90%) and enantiomeric excess (up to 95%). The
      extension of this methodology to ketones demonstrated the need for electrophilic
      ketones more reactive than acetophenone as the reaction would not proceed with
      just acetophenone. Using the Lewis acid indium triflate [In(OTf)(3)] induced
      regioselective formation of the corresponding homoallenic alcohol product from
      acetophenone. However, this methodology demonstrated excellent chemoselectivity
      in formation of only the corresponding secondary homopropargylic alcohol product
      in the presence of a ketone functionality. Investigation of the organoindium
      intermediates under our reaction conditions shows the formation of allenylindium
      species, and we suggest that these species contain an indium(III) center. In
      addition, we have observed the presence of a shiny, indium(0) nugget throughout
      the reaction, irrespective of the stoichiometry, indicating disproportionation of
      indium halide byproduct formed during the reaction.

PMID- 22148264
TI  - Filling Royce's shoes.

PMID- 22148265
TI  - Cationic surface reconstructions on cerium oxide nanocrystals: an aberration
      corrected HRTEM study.
AB  - Instabilities of nanoscale ceria surface facets are examined on the atomic level.
      The electron beam and its induced atom migration are proposed as a readily
      available probe to emulate and quantify functional surface activity, which is
      crucial for, for example, catalytic performance. In situ phase contrast high
      resolution transmission electron microscopy with spherical aberration correction
      is shown to be the ideal tool to analyze cationic reconstruction. Hydrothermally
      prepared ceria nanoparticles with particularly enhanced {100} surface exposure
      are explored. Experimental analysis of cationic reconstruction is supported by
      molecular dynamics simulations where the Madelung energy is shown to be directly
      related to the binding energy, which enables one to generate a visual
      representation of the distribution of "reactive" surface oxygen.

PMID- 22148266
TI  - Influence of triplet state multidimensionality on excited state lifetimes of bis
      tridentate RuII complexes: a computational study.
AB  - Calculated triplet excited state potential energy surfaces are presented for a
      set of three bis-tridentate Ru(II)-polypyridyl dyes covering a wide range of room
      temperature excited state lifetimes: [Ru(II)(tpy)(2)](2+), 250 ps;
      [Ru(II)(bmp)(2)](2+), 15 ns; and [Ru(II)(dqp)(2)](2+), 3 MUs (tpy is 2,2':6',2"
      terpyridine, bmp is 6-(2-picolyl)-2,2'-bipyridine, and dqp is 2,6-di(quinolin-8
      yl)pyridine). The computational results provide a multidimensional view of the
      (3)MLCT-(3)MC transition for the investigated complexes. Recently reported
      results of significantly prolonged (3)MLCT excited state lifetimes of bis
      tridentate Ru(II)-complexes, for example [Ru(II)(dqp)(2)](2+), are found to
      correlate with substantial differences in their triplet excited state
      multidimensional potential energy surfaces. In addition to identification of low
      energy transition paths for (3)MLCT-(3)MC conversion associated with simultaneous
      elongation of two or more Ru-N bonds for all investigated complexes, the
      calculations also suggest significant differences in (3)MLCT state volume in the
      multidimensional reaction coordinate space formed from various combinations of Ru
      N bond distance variations. This is proposed to be an important aspect for
      understanding the large differences in experimentally observed (3)MLCT excited
      state lifetimes. The results demonstrate the advantage of considering
      multidimensional potential energy surfaces beyond the Franck-Condon region in
      order to predict photophysical and photochemical properties of bis-tridentate
      Ru(II)-polypyridyl dyes and related metal complexes.

PMID- 22148267
TI  - Deposition of brominated flame retardants to the Devon Ice Cap, Nunavut, Canada.
AB  - Brominated flame retardants (BFRs) can be transported to Arctic regions via
      atmospheric long-range transport, however, relatively little is known about their
      deposition to terrestrial environments. Snow cores from the Devon Ice Cap in
      Nunavut, Canada served to determine the recent depositional trends of BFRs. Snow
      pits were dug in 2005, 2006, and 2008. Dating using annual snow accumulation
      data, ion chemistry, and density measurements established that the pits covered
      the period from approximately 1993 to spring 2008. Samples were extracted under
      clean room conditions, and analyzed using GC-negative ion MS for 26 tri- to
      decabromodiphenyl ethers (BDEs), as well as other BFRs, nonbrominated flame
      retardants, and industrial chemicals. Decabromodiphenyl ether (BDE-209) was the
      major congener present in all samples followed by nona-BDEs (BDE-207, BDE-206,
      and BDE-208), both accounting for 89% and 7% of total BDE, respectively. BDE-209
      concentrations were in most cases significantly correlated (P < 0.05) to tri- to
      nona-BDE homologues, and the strength of the correlations increased with
      increasing degree of bromination. Prior to or after deposition BDE-209 may be
      subject to debromination to lighter congeners. Deposition fluxes of BDE-209 show
      no clear temporal trend and range between 90 and 2000 pg.cm(-2).year(-1). Back
      trajectory origin in densely populated areas of northeastern North America is
      significantly correlated (P < 0.005) with the BDE-209 deposition flux. Several
      other high production volume and/or alternative BFRs such as
      hexabromocyclododecane (HBCD), 1,2-bis(2,4,6-dibromophenoxy)ethane (BTBPE),
      pentabromo ethyl benzene (PBEBz), and pentabromobenzene (PBBz), as well as the
      industrial chemical 1,3,5-tribromobenzene (135-TBBz) were found consistently in
      the snow pits.

PMID- 22148268
TI  - Nickel-catalyzed synthesis of aryl trifluoromethyl sulfides at room temperature.
AB  - Inexpensive nickel-bipyridine complexes were found to be active for the
      trifluoromethylthiolation of aryl iodides and aryl bromides at room temperature
      using the convenient [NMe(4)][SCF(3)] reagent.

PMID- 22148269
TI  - Mode of action of cationic antimicrobial peptides defines the tethering position
      and the efficacy of biocidal surfaces.
AB  - Covalent immobilization of cationic antimicrobial peptides (CAPs) at sufficient
      density and distance from the solid matrix has been suggested as a successful
      strategy for the generation of biocidal surfaces. To test the hypothesis that the
      mode of peptide action is decisive for the selection of an appropriate tethering
      position on solid surfaces, melittin (MEL), a channel-forming peptide, buforin 2
      (BUF2), a peptide able to translocate bacterial membranes without
      permeabilization and targeting nucleic acids, and tritrpticin (TP), described to
      be membrane-lytic and to have intracellular targets, were C- and N-terminally
      immobilized on TentaGel S NH(2) resin beads as model surface. The peptide termini
      were modified with aminooxyacetic acid (AOA) and coupled via oxime-forming
      ligation. The comparison of the activities of the three peptides and their AOA
      modified analogues with a KLAL model peptide which permeabilizes membranes by a
      so-called "carpet-like" mode provided the following results: The peptides in
      solution state were active against Bacillus subtilis and Escherichia coli at
      micromolar concentrations. MEL and TP but not BUF2-derived peptides permeabilized
      the inner and outer membrane of E. coli and enhanced the permeability of lipid
      bilayers at concentrations around their antimicrobial values (MICs).
      Immobilization reduced peptide activity to millimolar MICs. The activity
      reduction for KLAL was independent of the tethering position and comparably low,
      as reflected by a low ratio of MIC(tethered)/MIC(free). In contrary, the pore
      forming MEL was much less active when immobilized at the N-terminus compared with
      the C-terminally tethered peptide. C- and N-terminal TP tethering caused an
      identical but much pronounced activity decrease. The tethered BUF2 peptides were
      inactive at the tested concentrations suggesting that the peptides could not
      reach the intracellular targets. In conclusion, membrane active peptides seem to
      be most suitable for the generation of antimicrobial surfaces, but knowledge
      about their mode of membrane insertion and positioning is required to identify
      optimal tethering positions. The relationship between the mechanism of action and
      position of immobilization is highly relevant for the establishment of a general
      approach to obtain efficient biocidal solid matrices loaded with CAPs.

PMID- 22148270
TI  - Perspectives on medical education.

PMID- 22148271
TI  - This issue: perspectives on pediatric medical education.

PMID- 22148272
TI  - An 8-year-old boy with intermittent pain.

PMID- 22148273
TI  - An 8-year-old girl with headache and syncope.

PMID- 22148274
TI  - The value of community pediatricians to academic health centers.

PMID- 22148275
TI  - Parents as medical educators.

PMID- 22148276
TI  - Behavioral health screening and referral in the pediatric office.

PMID- 22148277
TI  - New paradigms in continuing medical education.

PMID- 22148278
TI  - Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa
      5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa
      1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of
      cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and fms-like tyrosine
      kinase-3 (FLT3) for the treatment of cancer.
AB  - Herein, we describe the design, synthesis, and SAR of a series of unique small
      molecule macrocycles that show spectrum selective kinase inhibition of CDKs,
      JAK2, and FLT3. The most promising leads were assessed in vitro for their
      inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and
      microsomal stability. This screening cascade revealed 26 h as a preferred
      compound with target IC(50) of 13, 73, and 56 nM for CDK2, JAK2 and FLT3,
      respectively. Pharmacokinetic (PK) studies of 26 h in preclinical species showed
      good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma
      (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h
      (SB1317/TG02) was progressed into development in 2010 and is currently undergoing
      phase 1 clinical trials in advanced leukemias and multiple myeloma.

PMID- 22148280
TI  - Triterpene galactosides of the pouoside class and corresponding aglycones from
      the sponge Lipastrotethya sp.
AB  - Nine new triterpene galactosides and aglycones, along with three known compounds
      from the rare pouoside class, were isolated from the tropical sponge
      Lipastrotethya sp. collected from Micronesia. The structures of these new
      compounds were determined by combined spectroscopic methods and designated as
      pouosides F-I (4, 8, 10, and 12) and pouogenins A-E (5-7, 9, and 11). The
      absolute configurations of the asymmetric centers and the cyclohexenone moiety,
      which had been previously undetermined, were assigned by NOESY analyses and
      Mosher's methods. Several of these compounds exhibited weak cytotoxicity against
      the K562 cell line.

PMID- 22148281
TI  - Efficient solvent-assisted post-treatment for molecular rearrangement of sprayed
      polymer field-effect transistors.
AB  - Polymer-based field-effect transistors are fabricated using the gas-assisted
      spray technique, and their performance is considerably improved when a solvent
      assisted post-treatment method, solvent sprayed overlayer (SSO), is used. The SSO
      method is a unique treatment that can facilitate chain packing to increase
      crystallinity within the sprayed polymer layers, which inherently have a
      kinetically trapped amorphous chain morphology with lack of crystallinity due to
      rapid solvent evaporation. The device performance was drastically improved after
      SSO relative to conventional post-treatment, thermal annealing (TA). This
      occurred because SSO can rearrange the polymer chains into a dominantly edge-on
      crystal orientation, which is preferential for charge transport, whereas TA
      increases the crystallinity without rearrangement of the crystal orientation
      resulting in a complex of edge-on and face-on. The development of edge-on crystal
      domains after SSO within the active layers was responsible for the significant
      improvement in performance. The SSO is a simple and effective post-treatment
      method that validates the use of spray process and holds promise for use in other
      high-throughput processes for OFETs fabrication.

PMID- 22148282
TI  - Chemical profile of white wines produced from 'Greco bianco' grape variety in
      different Italian areas by nuclear magnetic resonance (NMR) and conventional
      physicochemical analyses.
AB  - In this study the characterization of white wines produced from the monovarietal
      'Greco bianco' grape variety is presented for the first time. A total of 40
      commercial wines, from two different southern Italian regions, Calabria and
      Campania, from the same grape variety and two different vintages, were
      investigated. The analyses were performed by means of chromatographic methods,
      conventional analyses, and nuclear magnetic resonance (NMR) spectroscopy. No
      differentiation was observed according to the year of production but a
      significant discrimination was achieved using principal component analysis (PCA)
      and partial least squares-discriminant analysis (PLS-DA). In particular, PLS-DA
      allowed the selection of compounds (total acidity; citric, malic, succinic, and
      lactic acids; total polyphenol index; glucose and proline/arginine ratio) useful
      for differentiating the studied wines on the basis of geographical origin.

PMID- 22148285
TI  - pH- and concentration-programmable electrodialytic buffer generator.
AB  - We have presented in a companion paper a suppressor-based electrodialytic buffer
      generator (EBG) that can produce programmable pH gradients. Here we demonstrate a
      three-electrode EBG. In this three-compartment flow-through device, the central
      compartment is separated from the outer compartments with a cation-exchange
      membrane (CEM) and an anion-exchange membrane (AEM), respectively. One platinum
      electrode is disposed in each compartment. The flows through each compartment are
      independent. With appropriate solutions in each compartment, independent
      potentials are applied to the CEM and AEM electrodes with respect to the grounded
      central electrode. The CEM current and the AEM current can be independently
      manipulated to generate buffers with variable concentration and pH in the central
      compartment. Both the CEM and AEM currents can be positive or negative. For the
      CEM, a positive current (i(cat)(in)) indicates that cations are coming in from
      the CEM channel to the center. A negative current (i(cat)(out)) takes cations out
      of the center to the CEM channel. Similarly for the AEM, currents governing anion
      transport into the center channel from the AEM channel (AEM electrode negative)
      or the reverse (AEM electrode positive) are respectively denoted by i(an)(in) or
      i(an)(out). Most examples herein involve inward ion transport, referred to as the
      additive mode. Depending on whether i(cat)(in) <i(an)(in) or i(cat)(in) >
      i(an)(in), H(+)/O(2) and OH(-)/H(2) are respectively produced at the central
      electrode to maintain electroneutrality. Any gas formed is subsequently removed
      by a gas removal device. The pH of the central channel effluent is related to the
      ratio of the currents through the two membranes, while the generated
      concentration is controlled by the absolute value of the currents. The buffer
      concentration and pH can be varied in a controlled predictable manner. A pH span
      of 3-12 was attained and a phosphate buffer concentration up to 140 mM was
      generated. We demonstrate a variety of combined pH/concentration gradients from a
      mixture of ethylenediamine, citrate, and phosphate by manipulating i(cat)(in),
      which controls introduction of the ethylenediammonium ion, and i(an)(in), which
      controls the introduction of citrate and phosphate ions. We also demonstrate an
      additive-subtractive mode of operation where both inward and outward currents are
      used to add one type of ion while removing another type of ion to reproducibly
      generate pH/concentration gradients.

PMID- 22148284
TI  - Nonphotochemical base-catalyzed hydroxylation of 2,6-dichloroquinone by H2O2
      occurs by a radical mechanism.
AB  - Kinetic and structural studies have shown that peroxidases are capable of the
      oxidation of 2,4,6-trichlorophenol (2,4,6-TCP) to 2,6-dichloro-1,4-benzoquinone
      (2,6-DCQ). Further reactions of 2,6-DCQ in the presence of H(2)O(2) and OH(-)
      yield 2,6-dichloro-3-hydroxy-1,4-benzoquinone (2,6-DCQOH). The reactions of 2,6
      DCQ have been monitored spectroscopically [UV-visible and electron spin resonance
      (ESR)] and chromatographically. The hydroxylation product, 2,6-DCQOH, has been
      observed by UV-visible and characterized structurally by (1)H and (13)C NMR
      spectroscopy. The results are consistent with a nonphotochemical base-catalyzed
      oxidation of 2,6-DCQ at pH > 7. Because H(2)O(2) is present in peroxidase
      reaction mixtures, there is also a potential role for the hydrogen peroxide anion
      (HOO(-)). However, in agreement with previous work, we observe that the
      nonphotochemical epoxidation by H(2)O(2) at pH < 7 is immeasurably slow. Both
      room-temperature ESR and rapid-freeze-quench ESR methods were used to establish
      that the dominant nonphotochemical mechanism involves formation of a semiquinone
      radical (base -catalyzed pathway), rather than epoxidation (direct attack by
      H(2)O(2) at low pH). Analysis of the kinetics using an Arrhenius model permits
      determination of the activation energy of hydroxylation (E(a) = 36 kJ/mol), which
      is significantly lower than the activation energy of the peroxidase-catalyzed
      oxidation of 2,4,6-TCP (E(a) = 56 kJ/mol). However, the reaction is second order
      in both 2,6-DCQ and OH(-) so that its rate becomes significant above 25  degrees
      C due to the increased rate of formation of 2,6-DCQ that feeds the second-order
      process. The peroxidase used in this study is the dehaloperoxidase-hemoglobin
      (DHP A) from Amphitrite ornata , which is used to study the effect of a catalyst
      on the reactions. The control experiments and precedents in studies of other
      peroxidases lead to the conclusion that hydroxylation will be observed following
      any process that leads to the formation of the 2,6-DCQ at pH > 7, regardless of
      the catalyst used in the 2,4,6-TCP oxidation reaction.

PMID- 22148287
TI  - Coordination-chemistry control of proton conductivity in the iconic metal-organic
      framework material HKUST-1.
AB  - HKUST-1, a metal-organic framework (MOF) material containing Cu(II)-paddlewheel
      type nodes and 1,3,5-benzenetricarboxylate struts, features accessible Cu(II)
      sites to which solvent or other desired molecules can be intentionally
      coordinated. As part of a broader investigation of ionic conductivity in MOFs, we
      unexpectedly observed substantial proton conductivity with the "as synthesized"
      version of this material following sorption of methanol. Although HKUST-1 is
      neutral, coordinated water molecules are rendered sufficiently acidic by Cu(II)
      to contribute protons to pore-filling methanol molecules and thereby enhance the
      alternating-current conductivity. At ambient temperature, the chemical identities
      of the node-coordinated and pore-filling molecules can be independently varied,
      thus enabling the proton conductivity to be reversibly modulated. The proton
      conductivity of HKUST-1 was observed to increase by ~75-fold, for example, when
      node-coordinated acetonitrile molecules were replaced by water molecules. In
      contrast, the conductivity became almost immeasurably small when methanol was
      replaced by hexane as the pore-filling solvent.

PMID- 22148288
TI  - Structural heterogeneity in the collision complex between organic dyes and
      tryptophan in aqueous solution.
AB  - The heterogeneity on photoinduced electron transfer (PET) kinetics between a
      labeled fluorophore and an amino acid residue has been extensively studied in
      biopolymers. However in aqueous solutions, the heterogeneity on PET kinetics
      between a fluorophore and a quencher has rarely been reported. Herein, we
      selected four commonly used fluorophores, such as tetramethylrhodamine (TMR),
      Rhodamine B (RhB), Alexa fluor 546 (Alexa546), and Atto655, and studied their
      respective PET kinetics in 50 mM tryptophan solutions with femtosecond transient
      absorption spectroscopy to explore the structural heterogeneity in their
      corresponding collision complexes. We measured the decay of the first excited
      electronic state of respective fluorophore with and without 50 mM tryptophan in
      aqueous solutions, and derived the charge separation rate in their corresponding
      collision complexes. We found that the PET process of all selected fluorophores
      in 50 mM tryptophan solutions has two charge separation rates, which indicates
      that the relevant states in the collision complex between respective fluorophore
      and tryptophan have strong structural heterogeneity. These femtosecond PET
      measurements are in agreement with Vaiana's molecular dynamics simulation (J. Am.
      Chem. Soc.2003, 125, 14564). In addition, with the obtained PET kinetic
      parameters, we derived the relative brightness of the collision complex between
      respective fluorophore and tryptophan, which are important parameters for the PET
      based fluorescence correlation spectroscopy study involving these fluorophores in
      biopolymers.

PMID- 22148289
TI  - De novo synthesis of L-colitose and L-rhodinose building blocks.
AB  - A divergent, practical, and efficient de novo synthesis of fully functionalized L
      colitose (3,6-dideoxy-L-galactose), 2-epi-colitose (3,6-dideoxy-L-talose), and L
      rhodinose (2,3,6-trideoxy-L-galactose) building blocks has been achieved using
      inexpensive, commercially available (S)-ethyl lactate as the starting material.
      The routes center around a diastereoselective Cram-chelated allylation that
      provides a common homoallylic alcohol intermediate. Oxidation of this common
      intermediate finally resulted in the synthesis of the three monosaccharide
      building blocks.

PMID- 22148290
TI  - Subtle photochemical behavior in ferroin-bromate-benzoquinone reaction.
AB  - This study investigated the photochemical behavior of the ferroin-bromate
      benzoquinone reaction in a batch system, in which the reduction of ferriin was
      dominated by bromide ions rather than by organic substrates as known in most of
      bromate oscillators. The chemical oscillations exhibited ultrasensitive response
      to illumination, where both the oscillation frequency and lifetime were
      significantly increased by ceiling light with an intensity of less than 20
      MUW/cm(2). As the light intensity was increased, the influence of light evolved
      from constructive to inhibitory. At a constant illumination, the influence of
      light also underwent a transition from constructive to inhibitory when the acid
      concentration was increased from 0.03 to 0.09 M. NMR measurements and absorption
      spectroscopy indicated photoenhanced bromination of benzoquinone and
      photoenhanced reduction of ferriin by bromide ions.

PMID- 22148291
TI  - LC-MS/MS method for simultaneous determination on a dried blood spot of multiple
      analytes relevant for treatment monitoring in patients with tyrosinemia type I.
AB  - Tyrosinemia type 1 is caused by deficiency of fumarylacetoacetate hydrolase. The
      enzymatic defect impairs the conversion of fumarylacetoacetate to fumarate,
      causing accumulation of succinylacetone which induces severe liver and kidney
      dysfunction along with mutagenic changes and hepatocellular carcinoma. Treatment
      is based on nitisinone (NTBC), an enzymatic inhibitor which suppresses
      succinylacetone production. NTBC, which has dramatically changed the disease
      course improving liver and kidney functions and reducing risk of liver cancer,
      causes a side effect of the increase of tyrosine levels. Treatment is therefore
      based on the combination of NTBC with a protein-restricted diet to prevent the
      potential toxicity of excessive tyrosine accumulation. Long-term therapy requires
      a careful monitoring in blood of NTBC levels along with other disease biomarkers,
      which include succinylacetone, and a selected panel of circulating aminoacids. We
      have developed a straightforward and fast MS/MS method for the simultaneous
      determination of NTBC, succinylacetone, tyrosine, phenylalanine, and methionine
      on a dried blood spot requiring a 2 min run. A single assay suitable for
      quantitative evaluation of all biochemical markers is of great advance over
      conventional methods, especially in pediatric patients, since it reduces
      laboratory costs and blood sampling, is less invasive and particularly suitable
      for pediatric patients, and allows easier storage and shipping.

PMID- 22148292
TI  - Synthesis and biological evaluation of antibody conjugates of phosphate prodrugs
      of cytotoxic DNA alkylators for the targeted treatment of cancer.
AB  - The synthesis and biological evaluation of phosphate prodrugs of analogues of 1
      (CC-1065) and their conjugates with antibodies are described. The phosphate group
      on the 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) portion of the
      compounds confers enhanced solubility and stability in aqueous solutions. In the
      presence of phosphatases, these compounds convert into active DNA-alkylating
      agents. The synthesis of the prodrugs was achieved sequentially through coupling
      of CBI with a bis-indolyl moiety, followed by attachment of a thiol-containing
      linker, and conversion of the hydroxyl group of CBI into a phosphate prodrug. The
      linkers incorporated into the prodrugs enable conjugation to an antibody via
      either a stable disulfide or thioether bond, in aqueous buffer solutions
      containing as little as 5% organic cosolvent, resulting in exclusively monomeric
      and stable antibody-cytotoxic prodrug conjugates. Two disulfide-containing
      linkers differing in the degree of steric hindrance were used in antibody
      conjugates to test the effect of different rates of intracellular disulfide
      cleavage and effector release on biological activity. The prodrugs can be
      converted to the active cytotoxic compounds through the action of endogenous
      phosphatases. Antibody-prodrug conjugates displayed potent antigen-selective
      cytotoxic activity in vitro and antitumor activity in vivo.

PMID- 22148295
TI  - Currents.

PMID- 22148296
TI  - Photochemistry of petroleum in water.

PMID- 22148293
TI  - Atmospheric photosensitized heterogeneous and multiphase reactions: from outdoors
      to indoors.
AB  - This proposal involves direct photolysis processes occurring in the troposphere
      incorporating photochemical excitation and intermolecular energy transfer. The
      study of such processes could provide a better understanding of .OH radical
      formation pathways in the atmosphere and in consequence, of a more accurate
      prediction of the oxidative capacity of the atmosphere. Compounds that readily
      absorb in the tropospheric actinic window (ionic organic complexes, PAHs,
      aromatic carbonyl compounds) acting as potential photosensitizers of atmospheric
      relevant processes are explored. The impact of hotosensitation on relevant
      systems which could act as powerful atmospheric reactors,that is, interface ocean
      atmosphere, urban and forest surfaces and indoor air environments is also
      discussed.

PMID- 22148297
TI  - Proposed air toxics legislation.

PMID- 22148298
TI  - Blind technology transfer:  The Bhopal example.

PMID- 22148299
TI  - Occurrence of chlorinated polynuclear aromatic hydrocarbons in tap water.

PMID- 22148300
TI  - Henry's law constants for the polychlorinated biphenyls.

PMID- 22148301
TI  - Carbonized coal products as a source of aromatic hydrocarbons to sediments from a
      highly industrialized estuary.

PMID- 22148302
TI  - High molecular weight hydrocarbons including polycyclic aromatic hydrocarbons in
      natural gas from consumer distribution pipelines and in pipeline residue.

PMID- 22148303
TI  - X-ray photoelectron spectroscopy studies of coal fly ashes with emphasis on depth
      profiling of submicrometer particle size fractions.

PMID- 22148304
TI  - Variability of elemental concentrations in power plant ash.

PMID- 22148305
TI  - Mutagenic activity of the products of propylene photooxidation.

PMID- 22148306
TI  - Aqueous solubility and octan-1-ol-water partition coefficients of aliphatic
      hydrocarbons.

PMID- 22148308
TI  - Determination of equilibrium and rate constants for binding of a polychlorinated
      biphenyl congener by dissolved humic substances.

PMID- 22148307
TI  - Influence of aggregation on the uptake kinetics of phosphate by goethite.

PMID- 22148309
TI  - Toluene-humic acid association equilibria:  isopiestic measurements.

PMID- 22148310
TI  - Comment on "Comparison of the carcinogenic risks from fish vs. groundwater
      contamination by organic compounds.

PMID- 22148311
TI  - Rebuttal on:  "Comparison of the carcinogenic risks from fish vs. groundwater
      contamination by organic compounds".

PMID- 22148312
TI  - Comment on "Red herrings in acid rain research.

PMID- 22148313
TI  - Reply to comments on "Red herrings in acid rain research".

PMID- 22148314
TI  - Lithium peroxide surfaces are metallic, while lithium oxide surfaces are not.
AB  - The thermodynamic stability and electronic structure of 40 surfaces of lithium
      peroxide (Li(2)O(2)) and lithium oxide (Li(2)O) were characterized using first
      principles calculations. As these compounds constitute potential discharge
      products in Li-oxygen batteries, their surface properties are expected to play a
      key role in understanding electrochemical behavior in these systems. Stable
      surfaces were identified by comparing 23 distinct Li(2)O(2) surfaces and 17
      unique Li(2)O surfaces; crystallite areal fractions were determined through
      application of the Wulff construction. Accounting for the oxygen overbinding
      error in density functional theory results in the identification of several new
      Li(2)O(2) oxygen-rich {0001} and {1 100} terminations that are more stable than
      those previously reported. Although oxygen-rich facets predominate in Li(2)O(2),
      in Li(2)O stoichiometric surfaces are preferred, consistent with prior studies.
      Surprisingly, surface-state analyses reveal that the stable surfaces of Li(2)O(2)
      are half-metallic, despite the fact that Li(2)O(2) is a bulk insulator. Surface
      oxygens in these facets are ferromagnetic with magnetic moments ranging from 0.2
      to 0.5 MU(B). In contrast, the stable surfaces of Li(2)O are insulating and
      nonmagnetic. The distinct surface properties of these compounds may explain
      observations of electrochemical reversibility for systems in which Li(2)O(2) is
      the discharge product and the irreversibility of systems that discharge to
      Li(2)O. Moreover, the presence of conductive surface pathways in Li(2)O(2) could
      offset capacity limitations expected to arise from limited electron transport
      through the bulk.

PMID- 22148315
TI  - Confocal microscopy imaging of NR2B-containing NMDA receptors based on
      fluorescent ifenprodil-like conjugates.
AB  - We describe the synthesis and pharmacological characterization of a first
      generation of ifenprodil conjugates 4-7 as fluorescent probes for the confocal
      microscopy imaging of the NR2B-containing NMDA receptor. The fluorescein
      conjugate 6 displayed a moderate affinity for NMDAR but a high selectivity for
      the NR2B subunit and its NTD. Fluorescence imaging of DS-red labeled cortical
      neurons showed an exact colocalization of the probe 6 with small protrusions
      along the dendrites related to a specific binding on NR2B-containing NMDARs.

PMID- 22148316
TI  - Library-based discovery and characterization of daphnane diterpenes as potent and
      selective HIV inhibitors in Daphne gnidium.
AB  - Despite the existence of an extended armamentarium of effective synthetic drugs
      to treat HIV, there is a continuing need for new potent and affordable drugs.
      Given the successful history of natural product based drug discovery, a library
      of close to one thousand plant and fungal extracts was screened for
      antiretroviral activity. A dichloromethane extract of the aerial parts of Daphne
      gnidium exhibited strong antiretroviral activity and absence of cytotoxicity.
      With the aid of HPLC-based activity profiling, the antiviral activity could be
      tracked to four daphnane derivatives, namely, daphnetoxin (1), gnidicin (2),
      gniditrin (3), and excoecariatoxin (4). Detailed anti-HIV profiling revealed that
      the pure compounds were active against multidrug-resistant viruses irrespective
      of their cellular tropism. Mode of action studies that narrowed the site of
      activity to viral entry events suggested a direct interference with the
      expression of the two main HIV co-receptors, CCR5 and CXCR4, at the cell surface
      by daphnetoxin (1).

PMID- 22148317
TI  - Color combination of conductive polymers for black electrochromism.
AB  - Conducting polymers that absorb three primary colors, red, green, and blue (RGB),
      were introduced with a yellow electrochromic polymer (Y) for the preparation of
      black electrochromic devices. Red poly(3-hexylthiophene) (P3HT) and blue poly(3,4
      ethylenedioxythiophene) (PEDOT) were coated on one side of the electrode as a
      cathodically coloring electrochromic (EC) layer, while green poly(aniline-N
      butylsulfonate) (PANBS) and yellow EC poly{[1,3-bis(9',9'-dihexylfluoren-20
      yl)azulenyl]-alt-[2",7"-(9",9"-dihexylfluorenyl]} (PDHFA) were coated on the
      opposite electrode to complete a complementary EC device. The yellow PDHFA layer
      effectively compensated for absorption below 450 nm and above the 600 nm region,
      which was lacking in the RGB electrode. The resultant RGBY ECD provided a black
      color near the CIE black with L*, a*, and b* values of 32, -1.1, and 3.7,
      respectively, covering a broad absorption in the visible range in the colored
      state. The state of the black EC device was maintained, even after the
      electricity was turned off for 200 h, showing stable memory effect.

PMID- 22148318
TI  - Ferritin-based new magnetic force microscopic probe detecting 10 nm sized
      magnetic nanoparticles.
AB  - A single-molecule ferritin picking-up process was realized with the use of AFM,
      which was enhanced by employing controlled dendron surface chemistry. The
      approach enabled the placement of a single ferritin protein molecule at the very
      end of an AFM tip. When used for magnetic force microscopy (MFM) imaging, the
      tips were able to detect magnetic interactions of approximately 10 nm sized
      magnetic nanoparticles. The single ferritin tip also showed the characteristics
      of a "multifunctional" MFM probe that can sense the magnetic force from magnetic
      materials as well as detect the biomolecular interaction force with DNAs on the
      surface. The multifunctional tip enabled us not only to investigate the specific
      molecular interaction but also to image the magnetic interaction between the
      probe and the substrate, in addition to allowing the common capability of
      topographic imaging. Because the protein engineering of ferritin and the
      supporting coordination and conjugation chemistry are well-established, we
      envisage that it would be straightforward to extend this approach to the
      development of various single magnetic particle MFM probes of different
      compositions and sizes.

PMID- 22148320
TI  - Structural diversity, optical and magnetic properties of a series of manganese
      thioarsenates with 1,10-phenanthroline or 2,2'-bipyridine ligands: using
      monodentate methylamine as an alkalinity regulator.
AB  - The exploration in two hydro(solvo)thermal reaction systems
      As/S/Mn(2+)/phen/methylamine aqueous solution and As/S/Mn(2+)/2,2'-bipy/H(2)O
      affords five new manganese thioarsenates with diverse structures, namely,
      (CH(3)NH(3)){[Mn(phen)(2)](As(V)S(4))}.phen (1 and 1'),
      (CH(3)NH(3))(2){[Mn(phen)](2)(As(V)S(4))(2)} (2),
      {[Mn(phen)(2)](As(III)(2)S(4))}(n) (3), {[Mn(phen)](3)(As(III)S(3))(2)}.H(2)O
      (4), and {[Mn(2,2'-bipy)(2)](2)(As(V)S(4))}[As(III)S(S(5))] (5). Compound 1
      comprises a {[Mn(phen)(2)](As(V)S(4))}(-) complex anion, a monoprotonated
      methylamine cation and a phen molecule. Compound 2 contains a butterfly like
      {[Mn(phen)](2)(As(V)S(4))(2)}(2-) anion charge compensated by two monoprotonated
      methylamine cations. Compound 3 is a neutral chain formed by a helical
      (1)(infinity)(As(III)S(2)(-)) vierer chain covalently bonds to [Mn(II)(phen)](2+)
      complexes via all its terminal S atoms. Compound 4 features a neutral chain
      showing the stabilization of noncondensed (As(III)S(3))(3-) anions in the
      coordination of [Mn(II)(phen)](2+) complex cations. Compound 5 features a mixed
      valent As(III)/As(V) character and an interesting chalcogenidometalates
      structure, where a polycation formed by the connection of two [Mn(2,2'
      bipy)(2)](2+) complex cation and a (As(V)S(4))(3-) anion acts as a countercation
      for a polythioarsenate anion, [As(III)S(S(5))](-). The title compounds exhibit
      optical gaps in the range 1.58-2.48 eV and blue photoluminescence. Interestingly,
      compound 1 displays a weak second harmonic generation (SHG) response being about
      1/21 times of KTP (KTiOPO(4)). Magnetic measurements show paramagnetic behavior
      for 1 and dominant antiferromagnetic behavior for 2-5. Of particular interest is
      4, which is the first manganese chalcogenide showing spin-canting characteristic.

PMID- 22148319
TI  - 6-Benzylaminopurine delays senescence and enhances health-promoting compounds of
      harvested broccoli.
AB  - The effect of 6-benzylaminopurine (6-BA) on the color, antioxidant activity, and
      contents of total phenols, glucosinolate, and sulforaphane in broccoli florets
      was investigated. The results showed that 6-BA treatment markedly inhibited the
      increase of the L* value and malondialdehyde (MDA) content and retarded the
      decrease of the H value. 6-BA treatment reduced the rate of chlorophyll
      degradation by regulating the activities of chlorophyllase and Mg-dechelatase.
      When compared to control florets, the 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical-scavenging activity and the activities of superoxide dismutase (SOD),
      ascorbate peroxidase (APX), and catalase (CAT) were enhanced in florets treated
      with 6-BA, whereas the activity of peroxidase (POD) was significantly reduced.
      The contents of total phenols, glucosinolate, and sulforaphane in broccoli
      florets were also profoundly increased after treatment with 6-BA. These results
      indicated that 6-BA could maintain the quality, delay senescence, and improve the
      nutritional value of broccoli.

PMID- 22148322
TI  - Growth, structure, and thermal conductivity of yttria-stabilized hafnia thin
      films.
AB  - Yttria-stabilized hafnia (YSH) films of 90 nm thickness have been produced using
      sputter-deposition by varying the growth temperature (T(s)) from room-temperature
      (RT) to 400  degrees C. The effect of T(s) on the structure, morphology, and
      thermal conductivity of YSH films has been investigated. Structural studies
      indicate that YSH films crystallize in the cubic phase. The lattice constant
      decreases from 5.15 to 5.10 A with increasing T(s). The average grain size (L)
      increases with increasing T(s); L-T(s) relationship indicates the thermally
      activated process of the crystallization of YSH films. The analyses indicate a
      critical temperature to promote nanocrystalline, cubic YSH films is 300  degrees
      C, which is higher compare to that of pure monoclinic HfO(2) films. Compared to
      pure nanocrystalline hafnia, the addition of yttria lowers the effective thermal
      conductivity. The effect of grain size on thermal conductivity is also explored.

PMID- 22148321
TI  - Effects of carbon-metal-carbon linkages on the optical, photophysical, and
      electrochemical properties of phosphametallacycle-linked coplanar porphyrin
      dimers.
AB  - 5-(Diphenylphosphanyl)-10,15,20-triarylporphyrins (meso-phosphanylporphyrins)
      underwent complexations with palladium(II) and platinum(II) salts to afford
      phosphapalladacycle- and phosphaplatinacycle-fused coplanar porphyrin dimers,
      respectively, via regioselective peripheral beta-C-H activation of the meso
      phosphanylporphyrin ligands. The optical and electrochemical properties of these
      metal-linked porphyrin dimers as well as their porphyrin monomer/dimer references
      were investigated by means of steady-state UV-vis absorption/fluorescence
      spectroscopy, cyclic and differential pulse voltammetry, time-resolved
      spectroscopy (fluorescence and transient absorption lifetimes and spectra), and
      magnetic circular dichroism spectroscopy. All the observed data clearly show that
      the palladium(II) and platinum(II) linkers play crucial roles in the electronic
      communication between two porphyrin chromophores at the one-electron oxidized
      state and in the singlet-triplet intersystem-crossing process at the excited
      state. It has also been revealed that the C-Pt-C linkage makes more significant
      impacts on these fundamental properties than the C-Pd-C linkage. Furthermore,
      density functional theory calculations on the metal-linked porphyrin dimers have
      suggested that the antibonding dpi-ppi orbital interaction between the
      peripherally attached metal and adjacent pyrrolic beta-carbon atoms destabilizes
      the highest occupied molecular orbitals of the porphyrin pi-systems and accounts
      for the observed unique absorption properties. On the basis of these experimental
      and theoretical results, it can be concluded that the linear carbon-metal-carbon
      linkages weakly but definitely perturb the optical, photophysical, and
      electrochemical properties of the phosphametallacycle-linked coplanar porphyrin
      dimers.

PMID- 22148324
TI  - Three-dimensional a-Si:H solar cells on glass nanocone arrays patterned by self
      assembled Sn nanospheres.
AB  - We introduce a cost-effective method of forming size-tunable arrays of nanocones
      to act as a three-dimensional (3D) substrate for hydrogenated amorphous silicon
      (a-Si:H) solar cells. The method is based on self-assembled tin nanospheres with
      sizes in the range of 20 nm to 1.2 MUm. By depositing these spheres on glass
      substrates and using them as an etch mask, we demonstrate the formation of glass
      nanopillars or nanocones, depending on process conditions. After deposition of
      150 nm thick a-Si:H solar cell p-i-n stacks on the glass nanocones, we show an
      output efficiency of 7.6% with a record fill factor of ~69% for a nanopillar
      based 3D solar cell. This represents up to 40% enhanced efficiency compared to
      planar solar cells and, to the best of our knowledge, is the first demonstration
      of nanostructured p-i-n a-Si:H solar cells on glass that is textured without
      optical lithography patterning methods.

PMID- 22148323
TI  - Maximizing lipophilic efficiency: the use of Free-Wilson analysis in the design
      of inhibitors of acetyl-CoA carboxylase.
AB  - This paper describes the design and synthesis of a novel series of dual
      inhibitors of acetyl-CoA carboxylase 1 and 2 (ACC1 and ACC2). Key findings
      include the discovery of an initial lead that was modestly potent and subsequent
      medicinal chemistry optimization with a focus on lipophilic efficiency (LipE) to
      balance overall druglike properties. Free-Wilson methodology provided a clear
      breakdown of the contributions of specific structural elements to the overall
      LipE, a rationale for prioritization of virtual compounds for synthesis, and a
      highly successful prediction of the LipE of the resulting analogues. Further
      preclinical assays, including in vivo malonyl-CoA reduction in both rat liver
      (ACC1) and rat muscle (ACC2), identified an advanced analogue that progressed to
      regulatory toxicity studies.

PMID- 22148325
TI  - Polyethylene crystallization nucleated by carbon nanotubes under shear.
AB  - Polyethylene crystallization under shear has been studied in the presence of
      single-wall, few-wall, and multiwall carbon nanotubes (SWNT, FWNT, and MWNT).
      Polyethylene crystal d-spacings for (110) and (200) planes in polyethylene/carbon
      nanotubes (CNT) are smaller than in the control polyethylene without CNT and the
      polymer chain is oriented along the CNT axis. The single-wall carbon nanotube
      templated polyethylene crystals do not redissolve in boiling xylenes; instead,
      the chain morphology transforms to an amorphous conformation but remains oriented
      along the nanotube axis. SWNT crystal peaks were also observed in
      polyethylene/SWNT fibers.

PMID- 22148326
TI  - Solid/liquid phase diagram of the ammonium sulfate/malic acid/water system.
AB  - We have studied the low temperature phase diagram and water activities of the
      ammonium sulfate/malic acid/water system using differential scanning calorimetry
      (DSC) and infrared spectroscopy (IR) of thin films. Using the results from our
      experiments we have mapped the ice primary phase region of the solid/liquid
      ternary phase diagram. In our DSC and IR experiments we observe ice nucleation in
      all samples and ammonium sulfate in some samples, which were cooled to 183 K.
      However, we only observed malic acid nucleation in IR experiments, where the
      sample was in contact with ZnSe windows. We also compare our results to the
      predictions of the Extended AIM Aerosol Thermodynamics Model (E-AIM) and find
      good agreement for the ice melting points in the ice primary phase field of this
      system; however, the E-AIM has difficulty predicting malic acid crystallization.

PMID- 22148327
TI  - Metal-free dihydroxylation of alkenes using cyclobutane malonoyl peroxide.
AB  - Cyclobutane malonoyl peroxide (7), prepared in a single step from the
      commercially available diacid 6, is an effective reagent for the dihydroxylation
      of alkenes. Reaction of a chloroform solution of 7 with an alkene in the presence
      of 1 equiv of water at 40  degrees C followed by alkaline hydrolysis leads to the
      corresponding diol (30-84%). With 1,2-disubstituted alkenes, the reaction
      proceeds with syn-selectivity (3:1 -> 50:1). A mechanism consistent with
      experimental findings is proposed, which is supported by deuterium and oxygen
      labeling studies and explains the stereoselectivity observed. Alternative
      reaction pathways that are dependent on the structure of the starting alkene are
      also described leading to the synthesis of allylic alcohols and gamma-lactones.

PMID- 22148331
TI  - Editorial. Chemistry and the quality of man's environment.

PMID- 22148329
TI  - Osmium bipyridine-containing redox polymers based on cellulose and their
      reversible redox activity.
AB  - Thermo-, pH-, and electrochemical-sensitive cellulose graft copolymers,
      hydroxypropyl cellulose-g-poly(4-vinylpyridine)-Os(bipyridine) (HPC-g-P4VP
      Os(bpy)), were synthesized and characterized. The electrochemical properties of
      the resulting material were investigated via cyclic voltammetry by coating the
      graft copolymers on the platinized carbon electrode. The results indicated that
      the electrochemical properties of the graft copolymer modified electrode were
      responsive to the pH values of the electrolyte solution. The reversible
      transformation between the active and inactive state originated from the changes
      in the architecture of the HPC-g-P4VP-Os(bpy) graft copolymer at different pH
      values. At high pH (e.g., above the pK(a) of P4VP), the chains of P4VP collapsed,
      and the electrochemical activity of the electrode was reduced. With
      immobilization of glucose oxidase (GOx) on the graft copolymer decorated
      electrode, a biosensor for glucose detection was prepared. The current of the
      biosensor depended on the glucose concentration in the detected solution and
      increased with the successive addition of glucose.

PMID- 22148332
TI  - Environmental currents.

PMID- 22148328
TI  - Contribution of coexisting sulfate and iron reducing bacteria to methylmercury
      production in freshwater river sediments.
AB  - We investigated microbial methylmercury (CH(3)Hg) production in sediments from
      the South River (SR), VA, an ecosystem contaminated with industrial mercury (Hg).
      Potential Hg methylation rates in samples collected at nine sites were low in
      late spring and significantly higher in late summer. Demethylation of (14)CH(3)Hg
      was dominated by (14)CH(4) production in spring, but switched to producing mostly
      (14)CO(2) in the summer. Fine-grained sediments originating from the erosion of
      river banks had the highest CH(3)Hg concentrations and were potential hot spots
      for both methylation and demethylation activities. Sequencing of 16S rRNA genes
      of cDNA recovered from sediment RNA extracts indicated that at least three groups
      of sulfate-reducing bacteria (SRB) and one group of iron-reducing bacteria (IRB),
      potential Hg methylators, were active in SR sediments. SRB were confirmed as a
      methylating guild by amendment experiments showing significant sulfate
      stimulation and molybdate inhibition of methylation in SR sediments. The addition
      of low levels of amorphous iron(III) oxyhydroxide significantly stimulated
      methylation rates, suggesting a role for IRB in CH(3)Hg synthesis. Overall, our
      studies suggest that coexisting SRB and IRB populations in river sediments
      contribute to Hg methylation, possibly by temporally and spatially separated
      processes.

PMID- 22148334
TI  - Feature. Industry and the pollution problem.

PMID- 22148333
TI  - Outlook.

PMID- 22148336
TI  - Laboratory method for predicting calcium sulfate scaling thresholds.

PMID- 22148335
TI  - Feature. Smog signals.

PMID- 22148337
TI  - Adsorption of viruses on activated carbon.  Equilibriums and kinetics of the
      attachment of Escherichia coli bacteriophage T4 on activated carbon.

PMID- 22148338
TI  - Biophysical limnology.  Separation of suspended and colloidal particles from
      natural water.

PMID- 22148339
TI  - Role of fluid properties in gas transfer.

PMID- 22148340
TI  - Thin-layer chromatographic method for estimation of chlorophenols.

PMID- 22148341
TI  - Effects of gaseous air pollutants on the response of the Thomas sulfur dioxide
      Autometer.

PMID- 22148342
TI  - Remote sensing and characterization of stack gases by infrared spectroscopy.  An
      approach by using multiple-scan interferometry.

PMID- 22148344
TI  - New  products.

PMID- 22148343
TI  - Evaluation of a visual color comparator method for determination of atmospheric
      nitrogen dioxide.

PMID- 22148345
TI  - New literature digest.

PMID- 22148346
TI  - ES Advisory Board Named.

PMID- 22148347
TI  - Bookshelf - congress looks at pollution control technology.

PMID- 22148348
TI  - Alginate sequencing: an analysis of block distribution in alginates using
      specific alginate degrading enzymes.
AB  - Distribution and proportion of beta-D-mannuronic and alpha-L-guluronic acid in
      alginates are important for understanding the chemical-physical properties of the
      polymer. The present state of art methods, which is based on NMR, provides a
      statistical description of alginates. In this work, a method was developed that
      also gives information of the distribution of block lengths of each of the three
      block types (M, G, and MG blocks). This was achieved using a combination of
      alginate lyases with different substrate specificities, including a novel lyase
      that specifically cleaves diguluronic acid linkages. Reaction products and
      isolated fragments of alginates degraded with these lyases were subsequently
      analyzed with (1)H NMR, HPAEC-PAD, and SEC-MALLS. The method was applied on three
      seaweed alginates with large differences in sequence parameters (F(G) = 0.32 to
      0.67). All samples contained considerable amounts of extremely long G blocks (DP
      > 100). The finding of long M blocks (DP >= 90) suggests that also algal
      epimerases act by a multiple attack mechanism. Alternating sequences (MG-blocks)
      were found to be much shorter than the other block types. In connection with
      method development, an oligomer library comprising both saturated and unsaturated
      oligomers of various composition and DP 2-15 was made.

PMID- 22148349
TI  - Gliotoxin analogues from a marine-derived fungus, Penicillium sp., and their
      cytotoxic and histone methyltransferase inhibitory activities.
AB  - Seven gliotoxin-related compounds were isolated from the fungus Penicillium sp.
      strain JMF034, obtained from deep sea sediments of Suruga Bay, Japan. These
      included two new metabolites, bis(dethio)-10a-methylthio-3a-deoxy-3,3a
      didehydrogliotoxin (1) and 6-deoxy-5a,6-didehydrogliotoxin (2), and five known
      metabolites (3-7). The structures of the new compounds were elucidated by
      analysis of spectroscopic data and the application of the modified Mosher's
      analysis. All of the compounds exhibited cytotoxic activity, whereas compounds
      containing a disulfide bond showed potent inhibitory activity against histone
      methyltransferase (HMT) G9a. None of them inhibited HMT SET7/9.

PMID- 22148350
TI  - Kinetics and thermodynamics of the thermal inactivation of polyphenol oxidase in
      an aqueous extract from Agaricus bisporus.
AB  - The kinetics and thermodynamics of the thermal inactivation of polyphenol oxidase
      (PPO) in an aqueous extract from mushroom Agaricus bisporus (J.E. Lange) Imbach
      was studied, using pyrocatechol as a substrate. Optimal conditions for enzymatic
      studies were determined to be pH 7.0 and 35-40  degrees C. The kinetics of PPO
      catalyzed oxidation of pyrocatechol followed the Haldane model with an optimum
      substrate concentration of 20 mM. Thermal inactivation of PPO was examined in
      more detail between 50 and 73  degrees C and in relation to exposure time.
      Obtained monophasic kinetics were adequately described by a first-order model,
      with significant inactivation occurring with increasing temperature (less than
      10% preserved activity after 6 min at 65  degrees C). Arrhenius plot
      determination and calculated thermodynamic parameters suggest that the PPO in
      aqueous extract from Agaricus bisporus mushroom is a structurally robust yet
      temperature-sensitive biocatalyst whose inactivation process is mainly entropy
      driven.

PMID- 22148351
TI  - Structure of the stapled p53 peptide bound to Mdm2.
AB  - Mdm2 is a major negative regulator of the tumor suppressor p53 protein, a protein
      that plays a crucial role in maintaining genome integrity. Inactivation of p53 is
      the most prevalent defect in human cancers. Inhibitors of the Mdm2-p53
      interaction that restore the functional p53 constitute potential nongenotoxic
      anticancer agents with a novel mode of action. We present here a 2.0 A resolution
      structure of the Mdm2 protein with a bound stapled p53 peptide. Such peptides,
      which are conformationally and proteolytically stabilized with all-hydrocarbon
      staples, are an emerging class of biologics that are capable of disrupting
      protein-protein interactions and thus have broad therapeutic potential. The
      structure represents the first crystal structure of an i, i + 7 stapled peptide
      bound to its target and reveals that rather than acting solely as a passive
      conformational brace, a staple can intimately interact with the surface of a
      protein and augment the binding interface.

PMID- 22148354
TI  - Matrix infrared spectroscopic and theoretical of the difluoroamino metal fluoride
      molecules: F2NMF (M = Cu, Ag, Au).
AB  - The difluoroamino coinage metal fluoride molecules  F(2)NMF (M = Cu, Ag, Au) have
      been made via spontaneous reactions of coinage metals and NF(3) in solid argon
      and neon matrixes during sample annealing without formation of the M(NF(3))
      complexes. Comparisons between the matrix infrared spectra and the density
      functional frequency calculations provide strong support for identification of
      the F(2)NMF molecules, which are found to have doublet ground states with C(2v)
      or near C(2v) geometries. The F(2)NCuF molecule can isomerize to the less stable
      FNCuF(2) isomer upon UV-visible irradiation, while no similar reactions were
      observed for the silver and gold species. The M-N bonds in the F(2)NMF molecules
      are stronger than those in the FNMF(2) isomers with the Ag-N bond being longest
      and weakest in both cases.

PMID- 22148353
TI  - Employing the metabolic "branch point effect" to generate an all-or-none, digital
      like response in enzymatic outputs and enzyme-based sensors.
AB  - Here, we demonstrate a strategy to convert the graded Michaelis-Menten response
      typical of unregulated enzymes into a sharp, effectively all-or-none response. We
      do so using an approach analogous to the "branch point effect", a mechanism
      observed in naturally occurring metabolic networks in which two or more enzymes
      compete for the same substrate. As a model system, we used the enzymatic reaction
      of glucose oxidase (GOx) and coupled it to a second, nonsignaling reaction
      catalyzed by the higher affinity enzyme hexokinase (HK) such that, at low
      substrate concentrations, the second enzyme outcompetes the first, turning off
      the latter's response. Above an arbitrarily selected "threshold" substrate
      concentration, the nonsignaling HK enzyme saturates leading to a "sudden"
      activation of the first signaling GOx enzyme and a far steeper dose-response
      curve than that observed for simple Michaelis-Menten kinetics. Using the well
      known GOx-based amperometric glucose sensor to validate our strategy, we have
      steepen the normally graded response of this enzymatic sensor into a discrete
      yes/no output similar to that of a multimeric cooperative enzyme with a Hill
      coefficient above 13. We have also shown that, by controlling the HK reaction we
      can precisely tune the threshold target concentration at which we observe the
      enzyme output. Finally, we demonstrate the utility of this strategy for achieving
      effective noise attenuation in enzyme logic gates. In addition to supporting the
      development of biosensors with digital-like output, we envisage that the use of
      all-or-none enzymatic responses will also improve our ability to engineer
      efficient enzyme-based catalysis reactions in synthetic biology applications.

PMID- 22148355
TI  - Rolling up gold nanoparticle-dressed DNA origami into three-dimensional plasmonic
      chiral nanostructures.
AB  - Construction of three-dimensional (3D) plasmonic architectures using structural
      DNA nanotechnology is an emerging multidisciplinary area of research. This
      technology excels in controlling spatial addressability at sub-10 nm resolution,
      which has thus far been beyond the reach of traditional top-down techniques. In
      this paper, we demonstrate the realization of 3D plasmonic chiral nanostructures
      through programmable transformation of gold nanoparticle (AuNP)-dressed DNA
      origami. AuNPs were assembled along two linear chains on a two-dimensional
      rectangular DNA origami sheet with well-controlled positions and particle
      spacing. By rational rolling of the 2D origami template, the AuNPs can be
      automatically arranged in a helical geometry, suggesting the possibility of
      achieving engineerable chiral nanomaterials in the visible range.

PMID- 22148356
TI  - A pilot study testing a fall prevention intervention for older adults:
      determining the feasibility of a five-sensor motion detection system.
AB  - Interventions to prevent hospital-based falls in older adults are critically
      important to reduce morbidity, mortality, and health care costs. The purpose of
      this pilot study was to test the accuracy and acceptability of a wireless five
      sensor motion detection system (5S-MDS) for detecting falls. Wearable motion
      sensors, which measure and integrate movement in space, may identify human
      movement patterns that immediately precede falls, thus allowing prevention.
      However, sensors must be accurate, and older adults must find wearable sensors
      acceptable. This descriptive feasibility study recruited 5 healthy older adults
      (mean age = 69.6) who wore the 5S-MDS while performing 35 movement scenarios. All
      participants agreed the sensors were acceptable, and skin integrity was
      maintained for all. The 5S-MDS accurately reflected the patients' movements and
      was found acceptable to the older adults; thus, the 5S-MDS has potential as an
      early warning system for falls.

PMID- 22148357
TI  - The 2010 Doris Schwartz Gerontological Nursing Research Award: Kathleen Coen
      Buckwalter, Phd, RN, FAAN.

PMID- 22148358
TI  - Dementia revisited.

PMID- 22148359
TI  - Influence of magnetite stoichiometry on U(VI) reduction.
AB  - Hexavalent uranium (U(VI)) can be reduced enzymatically by various microbes and
      abiotically by Fe(2+)-bearing minerals, including magnetite, of interest because
      of its formation from Fe(3+) (oxy)hydroxides via dissimilatory iron reduction.
      Magnetite is also a corrosion product of iron metal in suboxic and anoxic
      conditions and is likely to form during corrosion of steel waste containers
      holding uranium-containing spent nuclear fuel. Previous work indicated
      discrepancies in the extent of U(VI) reduction by magnetite. Here, we demonstrate
      that the stoichiometry (the bulk Fe(2+)/Fe(3+) ratio, x) of magnetite can, in
      part, explain the observed discrepancies. In our studies, magnetite stoichiometry
      significantly influenced the extent of U(VI) reduction by magnetite.
      Stoichiometric and partially oxidized magnetites with x >= 0.38 reduced U(VI) to
      U(IV) in UO(2) (uraninite) nanoparticles, whereas with more oxidized magnetites
      (x < 0.38) and maghemite (x = 0), sorbed U(VI) was the dominant phase observed.
      Furthermore, as with our chemically synthesized magnetites (x >= 0.38),
      nanoparticulate UO(2) was formed from reduction of U(VI) in a heat-killed
      suspension of biogenic magnetite (x = 0.43). X-ray absorption and Mossbauer
      spectroscopy results indicate that reduction of U(VI) to U(IV) is coupled to
      oxidation of Fe(2+) in magnetite. The addition of aqueous Fe(2+) to suspensions
      of oxidized magnetite resulted in reduction of U(VI) to UO(2), consistent with
      our previous finding that Fe(2+) taken up from solution increased the magnetite
      stoichiometry. Our results suggest that magnetite stoichiometry and the ability
      of aqueous Fe(2+) to recharge magnetite are important factors in reduction of
      U(VI) in the subsurface.

PMID- 22148362
TI  - Theoretical studies on the unimolecular decomposition of ethylene glycol.
AB  - The unimolecular decomposition processes of ethylene glycol have been
      investigated with the QCISD(T) method with geometries optimized at the B3LYP/6
      311++G(d,p) level. Among the decomposition channels identified, the H(2)O
      elimination channels have the lowest barriers, and the C-C bond dissociation is
      the lowest-energy dissociation channel among the barrierless reactions (the
      direct bond cleavage reactions). The temperature and pressure dependent rate
      constant calculations show that the H(2)O-elimination reactions are predominant
      at low temperature, whereas at high temperature, the direct C-C bond dissociation
      reaction is dominant. At 1 atm, in the temperature range 500-2000 K, the
      calculated rate constant is expressed to be 7.63 * 10(47)T(-10.38) exp(-42262/T)
      for the channel CH(2)OHCH(2)OH -> CH(2)CHOH + H(2)O, and 2.48 * 10(51)T(-11.58)
      exp(-43593/T) for the channel CH(2)OHCH(2)OH -> CH(3)CHO + H(2)O, whereas for the
      direct bond dissociation reaction CH(2)OHCH(2)OH -> CH(2)OH + CH(2)OH the rate
      constant expression is 1.04 * 10(71)T(-16.16) exp(-52414/T).

PMID- 22148360
TI  - Credneramides A and B: neuromodulatory phenethylamine and isopentylamine
      derivatives of a vinyl chloride-containing fatty acid from cf. Trichodesmium sp.
      nov.
AB  - Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were
      isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and
      expand a recently described class of vinyl chloride-containing natural products.
      The precursor fatty acid, credneric acid (3), was isolated from both the aqueous
      and organic fractions of the parent fraction as well as from another
      geographically and phylogenetically distinct cyanobacterial collection (Panama).
      Credneramides A and B inhibited spontaneous calcium oscillations in murine
      cerebrocortical neurons at low micromolar concentrations (1, IC(50) 4.0 MUM; 2,
      IC(50) 3.8 MUM).

PMID- 22148364
TI  - Chemical conversion synthesis of ZnS shell on ZnO nanowire arrays: morphology
      evolution and its effect on dye-sensitized solar cell.
AB  - Heterostructured ZnO/ZnS core/shell nanowire arrays have been successfully
      fabricated to serve as photoanode for the dye-sensitized solar cells (DSSCs) by a
      facile two-step approach, combining hydrothermal deposition and liquid-phase
      chemical conversion process. The morphology evolution of the ZnS coated on the
      ZnO nanowires and its effect on the performance of the DSSCs were systematically
      investigated by varying the reaction time during the chemical conversion process.
      The results show that the compact ZnS shell can effectively promote the
      photogenerated electrons transfer from the excited dye molecules to the
      conduction band of the ZnO, simultaneously suppress the recombination for the
      injected elelctrons from the dye and the redox electrolyte. As reaction time goes
      by, the surface of the nanowires becomes coarse because of the newly formed ZnS
      nanoparticles, which will enhance the dye loading, resulting in increment of the
      short-circuit current density (J(SC)) . Open-circuit photovoltage decay
      measurements also show that the electron lifetime (tau(n)) in the ZnO/ZnS
      core/shell nanostructures can be significantly prolonged because of the lower
      surface trap density in the ZnO after ZnS coating. For the ZnO/ZnS core/shell
      nanostructures, the J(SC) and eta can reach a maximum of 8.38 mA/cm(2) and 1.92%
      after 6 h conversion time, corresponding to 12- and 16-fold increments of as
      synthesized ZnO, respectively.

PMID- 22148365
TI  - Modeling and development of a biosensor based on optical relaxation measurements
      of hybrid nanoparticles.
AB  - We present a new approach for homogeneous real-time immunodiagnostics (denoted as
      "PlasMag") that can be directly carried out in sample solutions such as serum,
      thus promising to circumvent the need of sample preparation. It relies on highly
      sensitive plasmon-optical detection of the relaxation dynamics of magnetic
      nanoparticles immersed in the sample solution, which changes when target
      molecules bind to the surfaces of the nanoparticles due to the increase in their
      hydrodynamic radii. This method requires hybrid nanoparticles that combine both
      magnetic and optical anisotropic properties. Our model calculations show that
      core-shell nanorods with a cobalt core diameter of 6 nm, a cobalt core length of
      80 nm, and a gold shell thickness of 5 nm are ideally suited as nanoprobes. On
      the one hand, the spectral position of the longitudinal plasmon resonance of such
      nanoprobes lies in the near-infrared, where the optical absorption in serum is
      minimal. On the other hand, the expected change in their relaxation properties on
      analyte binding is maximal for rotating magnetic fields as excitation in the
      lower kHz regime. In order to achieve high alignment ratios of the nanoprobes,
      the strength of the magnetic field should be around 5 mT. While realistic
      distributions of the nanoprobe properties result in a decrease of their mean
      optical extinction, the actual relaxation signal change on analyte binding is
      largely unaffected. These model calculations are supported by measurements on
      plain cobalt nanorod dispersions, which are the base component of the aspired
      core-shell nanoprobes currently under development.

PMID- 22148368
TI  - Editorial - Countdown for Positive Pollution Control is Well Under Way.

PMID- 22148366
TI  - Nitromethane with IBX/TBAF as a nitrosating agent: synthesis of nitrosamines from
      secondary or tertiary amines under mild conditions.
AB  - Aliphatic or aromatic N,N-disubstituted nitrosamine was generated in fair to
      excellent yield from the reaction of a secondary or tertiary amine with o
      iodoxybenzoic acid (IBX) or o-iodosylbenzoic acid (IBA)/R(4)NX (X = halide) and
      nitromethane. The product yield was strongly influenced by both the halide of
      R(4)NX and iodanes. IBX gave a higher yield than IBA, while the halides follow F(
      ) > Cl(-) > Br(-) ~ I(-). Nitrous acid formed in situ from nitromethane and IBX
      (or IBA)/halides is likely responsible for the observed reaction.

PMID- 22148369
TI  - Environmental currents.

PMID- 22148370
TI  - Preserve a living laboratory.

PMID- 22148371
TI  - Water management - a fashionable topic.

PMID- 22148373
TI  - Quote...Time to develop an urban land policy.

PMID- 22148372
TI  - Market for water pollution control equipment burgeons.

PMID- 22148374
TI  - Radio station fires a broadside at regional air pollution problems.

PMID- 22148375
TI  - Air pollution studies can be aided by an overall air pollution index.

PMID- 22148376
TI  - Response of single particle optical counters to nonideal particles.

PMID- 22148377
TI  - Proximate calculation of the solubility of gypsum in natural brines from
      28.degree. to 70.degree.

PMID- 22148378
TI  - Biodegradation of nitrilotriacetate in activated sludge.

PMID- 22148379
TI  - Gas chromatographic analysis of polycyclic aromatic hydrocarbons in soot samples.

PMID- 22148380
TI  - Catalytic combustion of ethylene on nickel oxide.

PMID- 22148381
TI  - Occurrence of beryllium as a trace element in environmental materials.

PMID- 22148384
TI  - New product digest.

PMID- 22148382
TI  - Photooxidation of formaldehyde at low partial pressures of aldehyde.

PMID- 22148385
TI  - New literature digest.

PMID- 22148386
TI  - Survey of mycotoxins in U.S. distiller's dried grains with solubles from 2009 to
      2011.
AB  - Distiller's dried grains with solubles (DDGS) is a major coproduct of the fuel
      ethanol industry and is becoming a popular low-cost ingredient for animal feed.
      Uncertainties regarding the risk factors in DDGS, such as level of mycotoxins,
      could limit its application in the animal feed industry. To provide a
      scientifically sound assessment of the prevalence and levels of mycotoxins in
      U.S. DDGS, we measured aflatoxins, deoxynivalenol, fumonisins, T-2 toxin, and
      zearalenone in 67 DDGS samples collected from 8 ethanol plants in the midwestern
      United States from 2009 to 2011. Among the five mycotoxins, deoxynivalenol was
      the main focus of the study because the crop year of 2009 was favorable for
      deoxynivalenol occurrence in corn. We learned that no more than 12% of the
      samples contained deoxynivalenol levels higher than the minimum advisory level
      for use in animal feed provided by the U.S. FDA, and the deoxynivalenol levels in
      all DDGS collected in 2011 were <2 mg/kg. Besides, intensive study showed that
      the enrichment of deoxynivalenol from contaminated corn to DDGS was about 3.5
      times. With regard to the other mycotoxins in DDGS, the study suggested that (1)
      almost none of the DDGS samples produced in 2010 contained detectable aflatoxins
      and the highest level of aflatoxins in DDGS was 5.7 MUg/kg; (2) no more than 6%
      of the samples contained fumonisin levels higher than the guidance level for
      feeding equids and rabbits provided by the U.S. FDA; (3) none of the samples
      contained T-2 higher than the detection limit; (4) most samples contained
      zearalenone levels between 100 and 300 MUg/kg. This study was based on
      representative DDGS samples from the U.S. ethanol industry, and the data were
      collected using state-of-the-art analytical methodology. This study provided a
      comprehensive and scientifically sound assessment of the occurrence and levels of
      mycotoxins in DDGS produced from 2009 to early 2011 by the U.S. ethanol industry.

PMID- 22148387
TI  - One-pot enantioselective synthesis of functionalized pyranocoumarins and 2-amino
      4H-chromenes: discovery of a type of potent antibacterial agent.
AB  - Function-oriented design and synthesis of chiral small molecules with novel
      activity is a key goal in modern organic chemistry. As multiple antibiotic
      resistant pathogens are emerging and causing serious diseases, the need for
      practical routes for the development of new types of antibacterial agents is very
      urgent. Herein, we present a highly efficient process for the synthesis of
      optically active pyranocoumarins and 2-amino-4H-chromenes through an
      organocatalytic Knoevenagel/Michael/cyclization sequence, and the preliminary
      biological studies of these new heterocyclic compounds revealed potent
      antibacterial activity. This study provides a novel strategy for further research
      and development of new types of antibacterial agents effective against human
      pathogens.

PMID- 22148388
TI  - A stepwise solvent-promoted SNi reaction of alpha-D-glucopyranosyl fluoride:
      mechanistic implications for retaining glycosyltransferases.
AB  - The solvolysis of alpha-d-glucopyranosyl fluoride in hexafluoro-2-propanol gives
      two products, 1,1,1,3,3,3-hexafluoropropan-2-yl alpha-d-glucopyranoside and 1,6
      anhydro-beta-D-glucopyranose. The ratio of these two products is essentially
      unchanged for reactions that are performed between 56 and 100  degrees C. The
      activation parameters for the solvolysis reaction are as follows: DeltaH(++) =
      81.4 +/- 1.7 kJ mol(-1), and DeltaS(++) = -90.3 +/- 4.6 J mol(-1) K(-1). To
      characterize, by use of multiple kinetic isotope effect (KIE) measurements, the
      TS for the solvolysis reaction in hexafluoro-2-propanol, we synthesized a series
      of isotopically labeled alpha-d-glucopyranosyl fluorides. The measured KIEs for
      the C1 deuterium, C2 deuterium, C5 deuterium, anomeric carbon, ring oxygen, O6,
      and solvent deuterium are 1.185 +/- 0.006, 1.080 +/- 0.010, 0.987 +/- 0.007,
      1.008 +/- 0.007, 0.997 +/- 0.006, 1.003 +/- 0.007, and 1.68 +/- 0.07,
      respectively. The transition state for the solvolysis reaction was modeled
      computationally using the experimental KIE values as constraints. Taken together,
      the reported data are consistent with the retained solvolysis product being
      formed in an S(N)i (D(N)(++)*A(Nss)) reaction with a late transition state in
      which cleavage of the glycosidic bond is coupled to the transfer of a proton from
      a solvating hexafluoro-2-propanol molecule. In comparison, the inverted product,
      1,6-anhydro-beta-D-glucopyranose, is formed by intramolecular capture of a
      solvent-equilibrated glucopyranosylium ion, which results from dissociation of
      the solvent-separated ion pair formed in the rate-limiting ionization reaction
      (D(N)(++) + A(N)). The implications that this model reaction have for the mode of
      action of retaining glycosyltransferases are discussed.

PMID- 22148389
TI  - Induction of oxidative DNA damage by flavonoids of propolis: its mechanism and
      implication about antioxidant capacity.
AB  - Propolis from beehives is commonly used as a home remedy for various purposes
      including as a topical antiseptic. Despite its antioxidant capacity, propolis
      induces oxidative DNA damage. In exploring the underlying mechanism, we found
      that the induction of oxidative DNA damage is attributed to the hydrogen peroxide
      (H(2)O(2)) produced by propolis. The formation of H(2)O(2) can take place without
      the participation of cells but requires the presence of transition metal ions
      such as iron. Flavonoids such as galangin, chrysin, and pinocembrin that are
      commonly detected in propolis have the capacity to induce oxidative DNA damage,
      and that capacity correlates with the production of H(2)O(2), suggesting the
      involvement of flavonoids in propolis in this process. On the basis of these
      results, we propose that the flavonoids of propolis serve as temporary carriers
      of electrons received from transition metal ions that are relayed to oxygen
      molecules to subsequently generate superoxide and H(2)O(2). In addition, propolis
      induces oxidative DNA damage that is subject to repair, and propolis-treated
      cells show a lower level of DNA damage level when challenged with another
      oxidative agent such as amoxicillin. This is reminiscent of an adaptive response
      that might contribute to the beneficial effects of propolis.

PMID- 22148390
TI  - Microfluidic lysis of human blood for leukocyte analysis using single cell
      impedance cytometry.
AB  - This paper demonstrates an integrated microfluidic system that performs a full
      blood count using impedance analysis. A microfluidic network design for red blood
      cell (RBC) lysis is presented, and the diffusive mixing processes are analyzed
      using experimental and simulated results. Healthy and clinical bloods analyzed
      with this system, and the data shows good correlation against data obtained from
      commercial hematology machines. The data from the microfluidic system was
      compared against hospital data for 18 clinical samples, giving R(2) (coefficient
      of determination) values of 0.99 for lymphocytes, 0.89 for monocytes, and 0.99
      for granulocytes in terms of relative counts and 0.94 for lymphocytes, 0.91 for
      monocytes, and 0.95 for granulocytes in terms of absolute counts. This
      demonstrates the potential clinical utility of this new system for a point-of
      care purpose.

PMID- 22148392
TI  - Role of protein dynamics in guiding electron-transfer pathways in reaction
      centers from Rhodobacter sphaeroides.
AB  - The role of protein dynamics in guiding multistep electron transfer is explored
      in the photosynthetic reaction center of  Rhodobacter sphaeroides . The
      energetics of the charge-separated intermediates, P(+)B(A)(-) and P(+)H(A)(-) (P
      is the initial electron donor bacteriochlorophyll pair and B(A) and H(A) are
      early bacteriochlorophyll and bacteriopheophytin acceptors, respectively), were
      systematically varied in a series of mutants. A fast phase of P(+)H(A)(-)
      recombination was resolved that is very sensitive to driving force. Either
      increasing or decreasing the relative free energy of P(+)H(A)(-) resulted in a
      more prominent fast recombination component, and thus a decreased yield forward
      electron transfer. The fast phase apparently represents P(+)H(A)(-) charge
      recombination via an activated state, probably P(+)B(A)(-) (B(A) is situated
      between P and H(A)). In wild type, this activated state is largely inaccessible,
      presumably due to dynamic stabilization of P(+)H(A)(-) within the first 100 ps.
      In mutants that change the energetics, the rate of decay via the activated state
      accelerates and that pathway becomes significant. The dynamic stabilization of
      the protein makes it possible to achieve a nearly optimum environment of H(A) in
      wild type on two different time scales and for two rather different reactions. On
      the picosecond time scale, the energetics is nearly, though not perfectly,
      optimized for transfer between the excited state of P and H(A). After dynamic
      stabilization of the state P(+)H(A)(-), the environment is optimized to avoid
      rapid recombination of the charge-separated state and instead carry out forward
      electron transfer to the quinone with very high yield on the hundreds of
      picosecond time scale. Thus, by employing protein dynamics, the reaction center
      is able to optimize multiple reactions, on very different time scales involving
      the same reaction intermediate.

PMID- 22148391
TI  - Structure-activity relationships for amide-, carbamate-, and urea-linked
      analogues of the tuberculosis drug (6S)-2-nitro-6-{[4
      (trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824).
AB  - Analogues of clinical tuberculosis drug (6S)-2-nitro-6-{[4
      (trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824),
      in which the OCH(2) linkage was replaced with amide, carbamate, and urea
      functionality, were investigated as an alternative approach to address oxidative
      metabolism, reduce lipophilicity, and improve aqueous solubility. Several soluble
      monoaryl examples displayed moderately improved (~2- to 4-fold) potencies against
      replicating  Mycobacterium tuberculosis  but were generally inferior inhibitors
      under anaerobic (nonreplicating) conditions. More lipophilic biaryl derivatives
      mostly displayed similar or reduced potencies to these in contrast to the parent
      biaryl series. The leading biaryl carbamate demonstrated exceptional metabolic
      stability and a 5-fold better efficacy than the parent drug in a mouse model of
      acute  M. tuberculosis  infection but was poorly soluble. Bioisosteric
      replacement of this biaryl moiety by arylpiperazine resulted in a soluble, orally
      bioavailable carbamate analogue providing identical activity in the acute model,
      comparable efficacy to OPC-67683 in a chronic infection model, favorable
      pharmacokinetic profiles across several species, and enhanced safety.

PMID- 22148393
TI  - Variables that influence cellular uptake and cytotoxic/cytoprotective effects of
      macrocyclic iron complexes.
AB  - Determination of the cellular uptake of macrocyclic iron(III) complexes by a
      facile method, accompanied by cell viability tests under both basal and induced
      oxidative stress, demonstrates that protection against intracellular oxidative
      stress requires reasonably high internalization and favorable anti/prooxidant
      profiles. Of the four tested complexes, only amphipolar iron(III) corrole met
      these criteria.

PMID- 22148394
TI  - Redox control of rotary motions in ferrocene-based elemental ball bearings.
AB  - Rotational motions of ferrocene-based carousels have been achieved by electron
      transfer centered on pi-dimerizable 4,4'-bipyridinium substituents introduced on
      both cyclopentadienyl rings through covalent linkers of different size, geometry,
      and flexibility. Detailed spectroscopic, electrochemical, and theoretical
      analyses demonstrate that rigid and fully conjugated linkers allow the
      quantitative formation of intramolecular pi-dimers resulting from optimized
      orbital overlaps within the HOMO of the electrochemically generated bis-radical
      species. The tetra-cationic "charge-repelled" conformers, the self-assembled pi
      dimers, and their electron triggered interconversions have been investigated by
      UV-vis, NMR, and ESR spectroscopy, electrochemistry, X-ray diffraction analysis,
      and theoretical calculations. These studies support the conclusion that the
      rotation of both cyclopentadienyl rings in ferrocene can be controlled
      electrochemically using noncovalent reversible interactions arising from pi
      radical coupling processes.

PMID- 22148395
TI  - Polyfluorinated compounds in serum linked to indoor air in office environments.
AB  - We aimed to investigate the role of indoor office air on exposure to
      polyfluorinated compounds (PFCs) among office workers. Week-long, active air
      sampling was conducted during the winter of 2009 in 31 offices in Boston, MA. Air
      samples were analyzed for fluorotelomer alcohols (FTOHs), sulfonamides (FOSAs),
      and sulfonamidoethanols (FOSEs). Serum was collected from each participant (n =
      31) and analyzed for 12 PFCs including PFOA and PFOS. In air, FTOHs were present
      in the highest concentrations, particularly 8:2-FTOH (GM = 9920 pg/m(3)). FTOHs
      varied significantly by building with the highest levels observed in a newly
      constructed building. PFOA in serum was significantly correlated with air levels
      of 6:2-FTOH (r = 0.43), 8:2-FTOH (r = 0.60), and 10:2-FTOH (r = 0.62).
      Collectively, FTOHs in air significantly predicted PFOA in serum (p < 0.001) and
      explained approximately 36% of the variation in serum PFOA concentrations. PFOS
      in serum was not associated with air levels of FOSAs/FOSEs. In conclusion, FTOH
      concentrations in office air significantly predict serum PFOA concentrations in
      office workers. Variation in PFC air concentrations by building is likely due to
      differences in the number, type, and age of potential sources such as carpeting,
      furniture, and/or paint.

PMID- 22148396
TI  - Hypoxylonols C-F, benzo[j]fluoranthenes from Hypoxylon truncatum.
AB  - Four novel benzo[j]fluoranthene derivatives, hypoxylonols C (3), D (4), E (5),
      and F (6), have been isolated from the mushroom Hypoxylon truncatum, together
      with two known benzo[j]fluoranthene derivatives, hypoxylonols A (1) and B (2).
      The structures were established by analysis of NMR spectroscopic data and X-ray
      diffraction data. Compounds 4 and 5 showed antiproliferative activity against
      HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical
      artery endothelial cells).

PMID- 22148398
TI  - Thin films of two functional oxides patterned laterally by soft lithography.
AB  - Thin films of two laterally patterned functional oxides of uniform thickness were
      obtained in a two-step soft-lithographic micromolding process. CoFe(2)O(4)/ZnO
      and CoFe(2)O(4)/BaTiO(3) dual-phase patterns were fabricated. The films showed
      good replication of the pattern that was defined in the first patterning step. X
      ray diffraction showed that the films consisted of two distinct phases, and
      magnetic force microscopy showed that the compounds were laterally separated, the
      separation pattern being the same as that of the initial soft-lithographic
      process. The films exhibited slight height variations near the edges of the
      phases, which were introduced in the first deposition step and were not fully
      compensated in the second deposition step. The films are sufficiently smooth to
      allow fabrication of multilayer structures.

PMID- 22148401
TI  - Editorial.  Industry publicly parades its air pollution control efforts.

PMID- 22148402
TI  - Environmental currents.

PMID- 22148403
TI  - Outlook.

PMID- 22148399
TI  - Trinucleotide repeat DNA alters structure to minimize the thermodynamic impact of
      8-oxo-7,8-dihydroguanine.
AB  - In the phenomenon of trinucleotide repeat (TNR) expansion, an important interplay
      exists between DNA damage repair of 8-oxo-7,8-dihydroguanine (8-oxoG) and
      noncanonical structure formation. We show that TNR DNA adapts its structure to
      accommodate 8-oxoG. Using chemical probe analysis, we find that CAG repeats
      composing the stem-loop arm of a three-way junction alter the population of
      structures in response to 8-oxoG by positioning the lesion at or near the loop.
      Furthermore, we find that oligonucleotides composed of odd-numbered repeat
      sequences, which form populations of two structures, will also alter their
      structure to place 8-oxoG in the loop. However, sequences with an even number of
      repeats do not display this behavior. Analysis by differential scanning
      calorimetry indicates that when the lesion is located within the loop, there are
      no significant changes to the thermodynamic parameters as compared to the DNA
      lacking 8-oxoG. This contrasts with the enthalpic destabilization observed when 8
      oxoG is base-paired to C and indicates that positioning 8-oxoG in the loop avoids
      the thermodynamic penalty associated with 8-oxoG base-pairing. Since formation of
      stem-loop hairpins is proposed to facilitate TNR expansion, these results
      highlight the importance of defining the structural consequences of DNA damage.

PMID- 22148404
TI  - Quote. The new professional - manager of environmental forces.

PMID- 22148405
TI  - Feature. Aquatic Life Water Quality Criteria.  ORSANCO - How it began.

PMID- 22148406
TI  - Chemical aspects of the photooxidation of the propylene-nitrogen oxide system.

PMID- 22148407
TI  - Method for sampling and determination of organic carbonyl compounds in automobile
      exhaust.

PMID- 22148408
TI  - Talc in atmospheric dusts.

PMID- 22148409
TI  - Extraction of organics from airborne particulates.  Effects of various solvents
      and conditions on the recovery of benzo[a]pyrene, benz[c]acridine, and 7H
      benz[d,e] anthracen-7-one.

PMID- 22148410
TI  - Natural radioactivity and cesium-137 in Alaskan caribou and reindeer samples.

PMID- 22148411
TI  - Concentrations of chromium, silver, molybdenum, nickel, cobalt, and manganese in
      suspended material in streams.

PMID- 22148413
TI  - New product digest.

PMID- 22148414
TI  - New literature digest.

PMID- 22148416
TI  - Stereospecific cross-coupling between alkenylboronates and alkyl halides
      catalyzed by iron-bisphosphine complexes.
AB  - A stereospecific and high-yielding cross-coupling reaction between alkenylboron
      reagents and alkyl halides is described. The reaction has been achieved by using
      well-defined iron-bisphosphine complexes such as 1b FeCl(2)(3,5-t-Bu(2)-SciOPP),
      which was recently developed by the authors' group. Various nonactivated alkyl
      bromides and chlorides possessing a base/nucleophile-sensitive functional group
      can participate in the cross-coupling, demonstrating its utility for
      stereoselective synthesis of functional molecules bearing a carbon-carbon double
      bond.

PMID- 22148415
TI  - Benzyl isothiocyanate (BITC) induces G2/M phase arrest and apoptosis in human
      melanoma A375.S2 cells through reactive oxygen species (ROS) and both
      mitochondria-dependent and death receptor-mediated multiple signaling pathways.
AB  - Benzyl isothiocyanates (BITC), a member of the isothiocyanate (ITC) family,
      inhibits cell growth and induces apoptosis in many types of human cancer cell
      lines. The present study investigated mechanisms underlying BITC-induced
      apoptosis in A375.S2 human melanoma cancer cells. To observe cell morphological
      changes and viability, flow cytometric assays, cell counting, and a contrast
      phase microscopic examination were carried out in A375.S2 cells after BITC
      treatment. Cell cycle distribution and apoptosis were assessed with the analysis
      of cell cycle by flow cytometric assays, DAPI staining, propidium iodide (PI),
      and annexin V staining. Apoptosis-associated factors such as reactive oxygen
      species (ROS) formation, loss of mitochondrial membrane potential (DeltaPsi(m)),
      intracellular Ca(2+) release, and caspase-3 activity were evaluated by flow
      cytometric assays. Abundance of cell cycle and apoptosis associated proteins was
      determined by Western blotting. AIF and Endo G expression was examined by
      confocal laser microscope. Results indicated that (1) BITC significantly reduced
      cell number and induced cell morphological changes in a dose-dependent manner in
      A375.S2 cells; (2) BITC induced arrest in cell cycle progression at G(2)/M phase
      through cyclin A, CDK1, CDC25C/Wee1-mediated pathways; (3) BITC induced apoptosis
      and increased sub-G(1) population; and (4) BITC promoted the production of ROS
      and Ca(2+) and loss of DeltaPsi(m) and caspase-3 activity. Furthermore, BITC
      induced the down-regulation of Bcl-2 expression and induced up-regulation of Bax
      in A375.S2 cells. Moreover, BITC-induced cell death was decreased after
      pretreatment with N-acetyl-l-cysteine (NAC, a ROS scavenger) in A375.S2 cells. In
      conclusion, the results showed that BITC promoted the induction of G(2)/M phase
      arrest and apoptosis in A375.S2 human melanoma cells through ER stress- and
      mitochondria-dependent and death receptor-mediated multiple signaling pathways.
      These data suggest that BITC has potential as an agent for the treatment of
      melanoma.

PMID- 22148418
TI  - Dielectric cell response in highly conductive buffers.
AB  - We present a novel method for the identification of live and dead T-cells,
      dynamically flowing within highly conductive buffers. This technique
      discriminates between live and dead (heat treated) cells on the basis of
      dielectric properties variations. The key advantage of this technique lies in its
      operational simplicity, since cells do not have to be resuspended in isotonic low
      conductivity media. Herein, we demonstrate that at 40 MHz, we are able to
      statistically distinguish between live and dead cell populations.

PMID- 22148419
TI  - Nickel-catalyzed C-H/C-O coupling of azoles with phenol derivatives.
AB  - The first nickel-catalyzed C-H bond arylation of azoles with phenol derivatives
      is described. The new Ni(cod)(2)/dcype catalytic system is active for the
      coupling of various phenol derivatives such as esters, carbamates, carbonates,
      sulfamates, triflates, tosylates, and mesylates. With this C-H/C-O biaryl
      coupling, we synthesized a series of privileged 2-arylazoles, including
      biologically active alkaloids. Moreover, we demonstrated the utility of the
      present reaction for functionalizing estrone and quinine.

PMID- 22148420
TI  - Hierarchically organized bimolecular ladder network exhibiting guided one
      dimensional diffusion.
AB  - The assembly and dynamics of a hierarchical, bimolecular network of sexiphenyl
      dicarbonitrile and N,N'-diphenyl oxalic amide molecules on the Ag(111) surface
      are studied by scanning tunneling microscopy at controlled temperature. The
      network formation is governed by a two-step protocol involving hierarchic
      interactions, including a novel carbonitrile-oxalic amide bonding motif. For
      temperatures exceeding ~70 K, more weakly bound sexiphenyl dicarbonitrile
      molecules carry out one-dimensional diffusion guided by the more stable
      substructure of the network held together by the carbonitrile-oxalic amide
      bonding motif. A theoretical investigation at the ab initio level confirms the
      different binding energies of the two coupling motifs and rationalizes the
      network formation and the diffusion pathway.

PMID- 22148421
TI  - Optimization of localized surface plasmon resonance transducers for studying
      carbohydrate-protein interactions.
AB  - Noble metal nanostructures supporting localized surface plasmons (SPs) have been
      widely applied to chemical and biological sensing. Changes in the refractive
      index near the nanostructures affect the SP extinction band, making localized
      surface plasmon resonance (LSPR) spectroscopy a convenient tool for studying
      biological interactions. Carbohydrate-protein interactions are of major
      importance in living organisms; their study is crucial for understanding of basic
      biological processes and for the construction of biosensors for diagnostics and
      drug development. Here LSPR transducers based on gold island films prepared by
      evaporation on glass and annealing were optimized for monitoring the specific
      interaction between Concanavalin A (Con A) and D-(+)-mannose. The sugar was
      modified with a PEG-thiol linker and immobilized on the Au islands. Sensing
      assays were performed under stationary and flow conditions, the latter providing
      kinetic parameters for protein binding and dissociation. Ellipsometry and Fourier
      transform-infrared (FT-IR) data, as well as scanning electron microscopy (SEM)
      imaging of fixated and stained samples, furnished independent evidence for the
      protein-sugar recognition. Enhanced response and visual detection of protein
      binding was demonstrated using Au nanoparticles stabilized with the linker
      modified mannose molecules. Mannose-coated transducers display an excellent
      selectivity toward Con A in the presence of a large excess of bovine serum
      albumin (BSA).

PMID- 22148422
TI  - Impact of functional satellite groups on the antimicrobial activity and
      hemocompatibility of telechelic poly(2-methyloxazoline)s.
AB  - Polyoxazolines with a biocidal quarternary ammonium end-group are potent
      biocides. Interestingly, the antimicrobial activity of the whole macromolecule is
      controlled by the nature of the group at the distal end. These nonreactive groups
      are usually introduced via the initiator. Here we present a study with a series
      of polymethyloxazolines with varying satellite groups introduced upon termination
      of the polymerization reaction. This allowed us to introduce a series of
      functional satellites, including hydroxy, primary amino, and double-bond
      containing groups. The resulting telechelic polyoxazolines were explored
      regarding their antimicrobial activity and toxicity. It was found that the
      functional satellite groups greatly controlled the minimal inhibitory
      concentrations against the bacteria Staphylococcus aureus and Escherichia coli in
      a range of 10 to 2500 ppm. Surprisingly, the satellite groups also controlled the
      hemotoxicity but in a different way than the antimicrobial efficiency.

PMID- 22148423
TI  - Photochemistry of benzylallene: ring-closing reactions to form naphthalene.
AB  - Conformer-specific, vibrationally resolved electronic spectroscopy of
      benzylallene (4-phenyl-1,2-butadiene) is presented along with a detailed analysis
      of the products formed via its ultraviolet photoexcitation. Benzylallene is the
      minor product of the recombination of benzyl and propargyl radicals. The mass
      selective resonant two-photon ionization spectrum of benzylallene was recorded
      under jet-cooled conditions, with its S(0)-S(1) origin at 37,483 cm(-1). UV-UV
      holeburning spectroscopy was used to show that only one conformer was present in
      the expansion. Rotational band contour analysis provided rotational constants and
      transition dipole moment direction consistent with a conformation in which the
      allene side chain is in the anti position, pointing away from the phenyl ring.
      The photochemistry of benzylallene was studied in a pump-probe geometry in which
      photoexcitation occurred by counter-propagating the expansion with a
      photoexcitation laser. The laser was timed to interact with the gas pulse in a
      short tube that extended the collisional region of the expansion. The products
      were cooled during expansion of the gas mixture into vacuum, before being
      interrogated using mass-selective resonant two-photon ionization. The UV-vis
      spectra of the photochemical products were compared to literature spectra for
      identification. Several wavelengths were chosen for photoexcitation, ranging from
      the S(0)-S(1) origin transition (266.79 nm) to 193 nm. Comparison of the product
      spectral intensities as a function of photoexcitation wavelength provides
      information on the wavelength dependence of the product yields. Photoexcitation
      at 266.79 nm yielded five products (benzyl radical, benzylallenyl radical, 1
      phenyl-1,3-butadiene, 1,2-dihydronaphthalene, and naphthalene), with naphthalene
      and benzylallenyl radicals dominant. At 193 nm, the benzylallenyl radical signal
      was greatly reduced in intensity, while three additional C(10)H(8) isomeric
      products were observed. An extensive set of calculations of key stationary points
      on the ground state C(10)H(10) and C(10)H(9) potential energy surfaces were
      carried out at the DFT B3LYP/6-311G(d,p) level of theory. Mechanisms for
      formation of the observed products are proposed based on these potential energy
      surfaces, constrained by the results of cursory studies of the photochemistry of
      1-phenyl-1,3-butadiene and 4-phenyl-1-butyne. A role for tunneling on the excited
      state surface in the formation of naphthalene is suggested by studies of
      partially deuterated benzylallene, which blocked naphthalene formation.

PMID- 22148424
TI  - Key mechanistic features of enantioselective C-H bond activation reactions
      catalyzed by [(chiral mono-N-protected amino acid)-Pd(II)] complexes.
AB  - Monoprotected chiral amino acids have recently been established as a class of
      ligand scaffolds for effecting Pd-catalyzed enantioselective C-H bond activation
      reactions. However, to elucidate the mechanistic details and controlling factors
      of these reactions, more comprehensive studies are needed. In this work we report
      computational investigations into the key mechanistic features of
      enantioselective C-H bond activation reactions catalyzed by a [chiral (mono-N
      protected amino acid)-Pd(II)] complex. Structural analysis points to a C-H
      insertion intermediate in which the nitrogen atom of the ligand is bound as a
      neutral sigma-donor. The formation of this C-H insertion intermediate could, in
      principle, proceed via a "direct C-H cleavage" or via "initial N-H bond cleavage
      followed by C-H cleavage". The computational studies presented herein show that
      the pathway initiated by N-H bond cleavage is more kinetically favorable. It is
      shown that the first step of the reaction is the N-H bond cleavage by the
      coordinated acetate group (OAc). In the next stage, the weakly coordinated OAc(-)
      (the second acetate group) activates the ortho-C-H bond of the substrate and
      transfers the H-atom from the C-atom to the bound N-atom of the ligand. As a
      result, a new Pd-C bond is formed and the carbamate is converted from X-type to L
      type ligand. The absolute configuration of the products that are predicted on the
      basis of the calculated energies of the transition states matches the
      experimental data. The calculated enantioselectivity is also comparable with the
      experimental result. On the basis of these data, the origin of the
      enantioselectivity can be largely attributed to steric repulsions in the
      transition states.

PMID- 22148425
TI  - A theoretical study of metal-metal cooperativity in the homogeneous water gas
      shift reaction.
AB  - The possibility of metal-metal cooperativity in improving the yield of the
      homogeneous water gas shift reaction (WGSR) has been investigated through full
      quantum mechanical density functional theory calculations. The calculations
      indicate that bimetallic catalysts would be likely to be more highly active than
      mononuclear metal-based catalysts for the WGSR. The results have implications for
      the design of improved WGSR catalysts in the future.

PMID- 22148426
TI  - Cross-validation of the structure of a transiently formed and low populated FF
      domain folding intermediate determined by relaxation dispersion NMR and CS
      Rosetta.
AB  - We have recently reported the atomic resolution structure of a low populated and
      transiently formed on-pathway folding intermediate of the FF domain from human
      HYPA/FBP11 [Korzhnev, D. M.; Religa, T. L.; Banachewicz, W.; Fersht, A. R.; Kay,
      L.E. Science 2011, 329, 1312-1316]. The structure was determined on the basis of
      backbone chemical shift and bond vector orientation restraints of the invisible
      intermediate state measured using relaxation dispersion nuclear magnetic
      resonance (NMR) spectroscopy that were subsequently input into the database
      structure determination program, CS-Rosetta. As a cross-validation of the
      structure so produced, we present here the solution structure of a mimic of the
      folding intermediate that is highly populated in solution, obtained from the wild
      type domain by mutagenesis that destabilizes the native state. The relaxation
      dispersion/CS-Rosetta structures of the intermediate are within 2 A of those of
      the mimic, with the nonnative interactions in the intermediate also observed in
      the mimic. This strongly confirms the structure of the FF domain folding
      intermediate, in particular, and validates the use of relaxation dispersion
      derived restraints in structural studies of invisible excited states, in general.

PMID- 22148427
TI  - Niphatenones, glycerol ethers from the sponge Niphates digitalis block androgen
      receptor transcriptional activity in prostate cancer cells: structure
      elucidation, synthesis, and biological activity.
AB  - Extracts of the marine sponge Niphates digitalis collected in Dominica showed
      strong activity in a cell-based assay designed to detect antagonists of the
      androgen receptor (AR) that could act as lead compounds for the development of a
      new class of drugs to treat castration recurrent prostate cancer (CRPC). Assay
      guided fractionation showed that niphatenones A (3) and B (4), two new glycerol
      ether lipids, were the active components of the extracts. The structures of 3 and
      4 were elucidated by analysis of NMR and MS data and confimed via total
      synthesis. Biological evaluation of synthetic analogues of the niphatenones has
      shown that the enantiomers 7 and 8 are more potent than the natural products in
      the screening assay and defined preliminary SAR for the new AR antagonist
      pharmacophore, including the finding that the Michael acceptor enone
      functionality is not required for activity. Niphatenone B (4) and its enantiomer
      8 blocked androgen-induced proliferation of LNCaP prostate cancer cells but had
      no effect on the proliferation of PC3 prostate cancer cells that do not express
      functional AR, consistent with activity as AR antagonists. Use of the propargyl
      ether 44 and Click chemistry showed that niphatenone B binds covalently to the
      activation function-1 (AF1) region of the AR N-terminus domain (NTD).

PMID- 22148430
TI  - Programming surface morphology of TiO2 hollow spheres and their superhydrophilic
      films.
AB  - Long-term stable superhydrophilic films without UV irradiation consisting of
      hierarchical raspberrylike metal-ion-doped TiO(2) hollow spheres were fabricated
      by a simple spinning-coat method. The hierarchical surface morphology of metal
      ion-doped TiO(2) hollow spheres can be programmed from "smooth", "moderate
      roughness" to "roughness" by adjusting the molar ratio of Co(2+) ions to Zn(2+)
      ions. Our results show that the substitution Co(2+) and Zn(2+) for Ti(4+) has
      effect on the phase transformation from anatase to rutile and further lead to
      different papillas on the surface of hollow nanospheres. And their films
      consisting of corresponding hollow nanospheres can be controlled from hydrophilic
      to superhydrophilic: 28, 7, and 0 degrees . Therefore, our works open an avenue
      to design hierarchical surface morphology of nanospheres and further fabricate
      antifogging superhydrophilic films.

PMID- 22148428
TI  - Exposure assessment for estimation of the global burden of disease attributable
      to outdoor air pollution.
AB  - Ambient air pollution is associated with numerous adverse health impacts.
      Previous assessments of global attributable disease burden have been limited to
      urban areas or by coarse spatial resolution of concentration estimates. Recent
      developments in remote sensing, global chemical-transport models, and
      improvements in coverage of surface measurements facilitate virtually complete
      spatially resolved global air pollutant concentration estimates. We combined
      these data to generate global estimates of long-term average ambient
      concentrations of fine particles (PM(2.5)) and ozone at 0.1 degrees  * 0.1
      degrees  spatial resolution for 1990 and 2005. In 2005, 89% of the world's
      population lived in areas where the World Health Organization Air Quality
      Guideline of 10 MUg/m(3) PM(2.5) (annual average) was exceeded. Globally, 32% of
      the population lived in areas exceeding the WHO Level 1 Interim Target of 35
      MUg/m(3), driven by high proportions in East (76%) and South (26%) Asia. The
      highest seasonal ozone levels were found in North and Latin America, Europe,
      South and East Asia, and parts of Africa. Between 1990 and 2005 a 6% increase in
      global population-weighted PM(2.5) and a 1% decrease in global population
      weighted ozone concentrations was apparent, highlighted by increased
      concentrations in East, South, and Southeast Asia and decreases in North America
      and Europe. Combined with spatially resolved population distributions, these
      estimates expand the evaluation of the global health burden associated with
      outdoor air pollution.

PMID- 22148431
TI  - Dihydroagarofuran derivatives from the dried roots of Tripterygium wilfordii.
AB  - Five new sesquiterpene derivatives, including dihydroagarofuran pyridine
      macrolides 1-4 and dihydroagarofuran ester 18, and 13 known dihydroagarofuran
      derivatives were isolated from the aqueous EtOH extract of the dried roots of
      Tripterygium wilfordii. An in vitro antiherpetic activity assay indicated that
      compounds 11 and 17 displayed weak and moderate inhibition against herpes simplex
      virus type II, respectively.

PMID- 22148432
TI  - Use of LC-MS/MS and stable isotopes to differentiate hydroxymethyl and methyl DNA
      adducts from formaldehyde and nitrosodimethylamine.
AB  - Formaldehyde is a known human and animal carcinogen that forms DNA adducts, and
      causes mutations. While there is widespread exposure to formaldehyde in the
      environment, formaldehyde is also an essential biochemical in all living cells.
      The presence of both endogenous and exogenous sources of formaldehyde makes it
      difficult to develop exposure-specific DNA biomarkers. Furthermore, chemicals
      such as nitrosodimethylamine form one mole of formaldehyde for every mole of
      methylating agent, raising questions about potential cocarcinogenesis.
      Formaldehyde-induced hydroxymethyl DNA adducts are not stable and need to be
      reduced to stable methyl adducts for detection, which adds another layer of
      complexity to identifying the origins of these adducts. In this study, highly
      sensitive mass spectrometry methods and isotope labeled compounds were used to
      differentiate between endogenous and exogenous hydroxymethyl and methyl DNA
      adducts. We demonstrate that N(2)-hydroxymethyl-dG is the primary DNA adduct
      formed in cells following formaldehyde exposure. In addition, we show that
      alkylating agents induce methyl adducts at N(2)-dG and N(6)-dA positions, which
      are identical to the reduced forms of hydroxymethyl adducts arising from
      formaldehyde. The use of highly sensitive LC-MS/MS and isotope labeled compounds
      for exposure solves these challenges and provides mechanistic insights on the
      formation and role of these DNA adducts.

PMID- 22148434
TI  - Charge transfer vibronic transitions in uranyl tetrachloride compounds.
AB  - The electronic and vibronic interactions of uranyl (UO(2))(2+) in three
      tetrachloride crystals have been investigated with spectroscopic experiments and
      theoretical modeling. Analysis and simulation of the absorption and
      photoluminescence spectra have resulted in a quantitative understanding of the
      charge transfer vibronic transitions of uranyl in the crystals. The spectra
      obtained at liquid helium temperature consist of extremely narrow zero-phonon
      lines (ZPL) and vibronic bands. The observed ZPLs are assigned to the first group
      of the excited states formed by electronic excitation from the 3sigma ground
      state into the f(delta,phi) orbitals of uranyl. The Huang-Rhys theory of vibronic
      coupling is modified successfully for simulating both the absorption and
      luminescence spectra. It is shown that only vibronic coupling to the axially
      symmetric stretching mode is Franck-Condon allowed, whereas other modes are
      involved through coupling with the symmetric stretching mode. The energies of
      electronic transitions, vibration frequencies of various local modes, and changes
      in the O?U?O bond length of uranyl in different electronic states and in
      different coordination geometries are evaluated in empirical simulations of the
      optical spectra. Multiple uranyl sites derived from the resolution of a
      superlattice at low temperature are resolved by crystallographic characterization
      and time- and energy-resolved spectroscopic studies. The present empirical
      simulation provides insights into fundamental understanding of uranyl electronic
      interactions and is useful for quantitative characterization of uranyl
      coordination.

PMID- 22148433
TI  - Phosphorylation of the p68 subunit of Pol delta acts as a molecular switch to
      regulate its interaction with PCNA.
AB  - DNA polymerase delta (Pol delta) is a central enzyme for eukaryotic DNA
      replication and repair. Pol delta is a complex of four subunits p125, p68, p50,
      and p12. The functional properties of Pol delta are largely determined by its
      interaction with its DNA sliding clamp PCNA (proliferating cellular nuclear
      antigen). The regulatory mechanisms that govern the association of Pol delta with
      PCNA are largely unknown. In this study, we identified S458, located in the PCNA
      interacting protein (PIP-Box) motif of p68, as a phosphorylation site for PKA.
      Phosphomimetic mutation of S458 resulted in a decrease in p68 affinity for PCNA
      as well as the processivity of Pol delta. Our results suggest a role of
      phosphorylation of the PIP-motif of p68 as a molecular switch that dynamically
      regulates the functional properties of Pol delta.

PMID- 22148435
TI  - Effects of micelle properties on the conformation of oligocholates and importance
      of rigidity of foldamers.
AB  - The conformation of a cholate hexamer with a clicked tether in between two
      tricholate units and pyrene groups at the chain ends was studied by fluorescence
      spectroscopy. In contrast to the parent cholate hexamer that folded in all
      micelles investigated, the folding of the clicked hexamer was highly dependent on
      the type of surfactant used to solubilize the compound. The clicked oligocholate
      folded in the Brij 35 micelle, possibly due to the latter's small size and strong
      internal hydrophobicity. The oligocholate formed intermolecular aggregates in SDS
      solutions below the CMC of the surfactant. The aggregates were dissociated by the
      SDS micelles but the individual oligocholate stayed unfolded. In Triton X-100 and
      sodium cholate solutions, the aggregated, unfolded, and folded oligocholates
      coexisted and gradual unfolding occurred with an increasing concentration of the
      surfactant. The conformation of the clicked oligocholate was sensitive to the
      nonideal mixing of ionic/nonionic micelles and to the unconventional aggregation
      of sodium cholate.

PMID- 22148438
TI  - Environmental currents.

PMID- 22148439
TI  - Outlook - demands for better water boost water treatment chemicals market.

PMID- 22148436
TI  - Heat treatment to modify the structural and physical properties of chitosan-based
      films.
AB  - This work was focused on studying the changes undergone by heat-treated chitosan
      films with and without tannic acid addition by monitoring both microstructure and
      physical properties. Once the films were submitted to different heat treatments,
      they exhibited higher barrier properties as well as lower water uptake,
      solubility, and moisture content. These results were also confirmed through X-ray
      patterns, which changed from the hydrated to the anhydrous conformation, sharper
      FTIR peaks specifically associated with water, and shift of T(g) toward higher
      temperatures determined by DMA. Moreover, the modifications caused by the curing
      process at a molecular scale were observed at a structural level by using a TEM
      technique. FTIR evaluation granted new insights into the interactions between
      tannic acid and chitosan molecules, before and after the heat curing, especially
      due to the occurrence of new peaks and changes in the wavenumber region 1550-1750
      cm(-1).

PMID- 22148440
TI  - Air Quality Criteria for Sulfur Oxides Set by HEW.

PMID- 22148441
TI  - Activated carbon used for large scale water treatment.

PMID- 22148442
TI  - Noise.

PMID- 22148443
TI  - Chemists discuss water resource management - 1. Chemistry of water pollution
      control: discovering the source and scope of chemical pollution.

PMID- 22148444
TI  - Chemists discuss water resource management - 2. Chemistry of ground waters:
      models for their composition.

PMID- 22148445
TI  - Chemists discuss water resource management - 3. The chemistry of rivers and
      lakes: the nature and properties of natural product organics and their role in
      metal-ion transport.

PMID- 22148446
TI  - Chemists discuss water resource management - 4. Chemistry of the oceans: some
      trace metal-organic associations and chemical parameter differences in top one
      meter of surface.

PMID- 22148447
TI  - Chemists discuss water resource management - 5. The analytical chemistry of water
      and waste waters.

PMID- 22148448
TI  - Application of subtractive techniques to the analysis of automotive exhaust.

PMID- 22148449
TI  - Modern instrumental techniques in the structure elucidation of products derived
      from petrochemicals.

PMID- 22148450
TI  - Gas sorption by a suspension of activated carbon in water.

PMID- 22148452
TI  - Selenium in the atmosphere.

PMID- 22148451
TI  - Adsorption of selected pesticides on activated carbon and mineral surfaces.

PMID- 22148453
TI  - Low-level Kjeldahl nitrogen determination on the technicon autoanalyzer.

PMID- 22148454
TI  - Water for Peace. The U. S. shifts gears.

PMID- 22148456
TI  - New literature digest.

PMID- 22148457
TI  - Bookshelf - pesticides:  an integrated control.

PMID- 22148458
TI  - Analysis of variance in spectroscopic imaging data from human tissues.
AB  - The analysis of cell types and disease using Fourier transform infrared (FT-IR)
      spectroscopic imaging is promising. The approach lacks an appreciation of the
      limits of performance for the technology, however, which limits both researcher
      efforts in improving the approach and acceptance by practitioners. One factor
      limiting performance is the variance in data arising from biological diversity,
      measurement noise or from other sources. Here we identify the sources of
      variation by first employing a high throughout sampling platform of tissue
      microarrays (TMAs) to record a sufficiently large and diverse set data. Next, a
      comprehensive  set of analysis of variance (ANOVA) models is employed to analyze
      the data. Estimating the portions of explained variation, we quantify the primary
      sources of variation, find the most discriminating spectral metrics, and
      recognize the aspects of the technology to improve. The study provides a
      framework for the development of protocols for clinical translation and provides
      guidelines to design statistically valid studies in the spectroscopic analysis of
      tissue.

PMID- 22148460
TI  - [18]/[20]pi hemiporphyrazine: a redox-switchable near-infrared dye.
AB  - An aromatic hemiporphyrazine with an 18pi-electron structure has been synthesized
      by oxidizing 20pi-electron 8,10,21,23-tetrahydroxy-28,30-dicarba-27H,29H
      hemiporphyrazine with bulky aryl ether substituents. The aromatic nature of the
      oxidized form was characterized by means of various spectroscopic methods and
      single-crystal X-ray analysis, with the help of quantum-chemical calculations.
      The oxidized hemiporphyrazine exhibited an intense absorption at ~850 nm. The
      redox process was found to be reversible.

PMID- 22148459
TI  - Probing quantum and dynamic effects in concerted proton-electron transfer
      reactions of phenol-base compounds.
AB  - The oxidation of three phenols, which contain an intramolecular hydrogen bond to
      a pendent pyridine or amine group, has been shown, in a previous experimental
      study, to undergo concerted proton-electron transfer (CPET). In this reaction,
      the electron is transferred to an outer-sphere oxidant, and the proton is
      transferred from the oxygen to nitrogen atom. In the present study, this reaction
      is studied computationally using a version of Hammes-Schiffer's multistate
      continuum theory where CPET is formulated as a transmission frequency between
      neutral and cation vibrational-electronic states. The neutral and cation proton
      vibrational wave functions are computed from one-dimensional potential energy
      surfaces (PESs) for the transferring proton in a fixed heavy atom framework. The
      overlap integrals for these neutral/cation wave functions, considering several
      initial (i.e., neutral) and final (i.e., cation) vibrational states, are used to
      evaluate the relative rates of oxidation. The analysis is extended to heavy atom
      configurations with various proton donor-acceptor (i.e., O-N) distances to assess
      the importance of heavy atom "gating". Such changes in d(ON) dramatically affect
      the nature of the proton PESs and wave functions. Surprisingly, the most reactive
      configurations have similar donor-acceptor distances despite the large (~0.2 A)
      differences in the optimized structures. These theoretical results qualitatively
      reproduce the experimental faster reactivity of the reaction of the pyridyl
      derivative 1 versus the CH(2)-pyridyl 2, but the computed factor of 5 is smaller
      than the experimental 10(2). The amine derivative is calculated to react
      similarly to 1, which does not agree with the experiments, likely due to some of
      the simplifying assumptions made in applying the theory. The computed kinetic
      isotope effects (KIEs) and their temperature dependence are in agreement with
      experimental results.

PMID- 22148461
TI  - Design of functionalized cellulosic honeycomb films: site-specific biomolecule
      modification via "click chemistry".
AB  - Value-added materials from naturally abundant polymers such as cellulose are of
      significant importance. In particular, cellulosic open-framework structures with
      controlled chemical functionality of the internal surface have great potential in
      many biosensor applications. Although various cellulose derivatives can form
      porous honeycomb structured materials, solubility issues and problems with film
      formation exist. To address this, we have generated robust cellulosic open
      framework structures that can be post-functionalized through site-specific
      modification. Regioselectively modified amphiphilic cellulose azides, 3-O
      azidopropoxypoly(ethylene glycol)-2,6-di-O-thexyldimethylsilyl cellulosics, were
      synthesized, and honeycomb-patterned films were readily produced by the simple
      breath figures method. Changing the degree of polymerization (DP) of the pendent
      ethylene glycol (EG(DP)) groups from 22 to 4 increased the corresponding
      honeycomb film pore diameters from ~1.2 to ~2.6 MUm, enabling the potential
      tuning of pore size. Moreover, these novel azido-functionalized honeycomb films
      were easily functionalized using Cu(I)-catalyzed alkyne-azide [2 + 3]
      cycloaddition reaction; biotin was "clicked" onto the azide functionalized
      cellulosic honeycomb films without any effect to the film structure. These
      results indicate this system may serve as a platform for the design and
      development of biosensors.

PMID- 22148462
TI  - DNA-directed assembly of asymmetric nanoclusters using Janus nanoparticles.
AB  - Asymmetric assembly of nanomaterials has attracted broad interests because of
      their unique anisotropic properties that are different from those based on the
      more widely reported symmetric assemblies. Despite the potential advantages,
      programmable fabrication of asymmetric structure in nanoscale remains a
      challenge. We report here a DNA-directed approach for the assembly of asymmetric
      nanoclusters using Janus nanoparticles as building blocks. DNA-functionalized
      spherical gold nanoparticles (AuNSs) can be selectively attached onto two
      different hemispheres of DNA-functionalized Janus nanoparticle (JNP) through DNA
      hybridization. Complementary and invasive DNA strands have been used to control
      the degree and reversibility of the assembly process through programmable base
      pairing interactions, resulting in a series of modular and asymmetric
      nanostructures that allow systematic study of the size-dependent assembly
      process. We have also shown that the attachment of the AuNSs onto the gold
      surface of the Janus nanoparticle results in red shifting of the UV-vis and
      plasmon resonance spectra.

PMID- 22148464
TI  - Enhancement of the visible-light photocatalytic activity of In2O3-TiO2 nanofiber
      heteroarchitectures.
AB  - One-dimensional In(2)O(3)-TiO(2) heteroarchitectures with high visible-light
      photocatalytic activity have been successfully obtained by a simple combination
      of electrospinning technique and solvothermal process. The as-obtained products
      were characterized by field emission scanning electron microscopy (FE-SEM),
      energy-dispersive X-ray (EDX) spectroscopy, transmission electron microscopy
      (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and UV
      vis spectra. The results revealed that the secondary In(2)O(3) nanostructures
      were successfully grown on the primary TiO(2) nanofibers substrates. Compared
      with the pure TiO(2) nanofibers, the obtained In(2)O(3)-TiO(2)
      heteroarchitectures showed enhancement of the visible-light photocatalytic
      activity to degrade rhodamine B (RB) because of the formation of
      heteroarchitectures, which might improve the separation of photogenerated
      electrons and holes derived from the coupling effect of TiO(2) and In(2)O(3)
      heteroarchitectures. Moreover, the In(2)O(3)-TiO(2) heteroarchitectures could be
      easily recycled without the decrease in the photocatalytic activity because of
      their one-dimensional nanostructural property.

PMID- 22148465
TI  - Synthesis, reactivity studies, structural aspects, and solution behavior of half
      sandwich ruthenium(II) N,N',N''-triarylguanidinate complexes.
AB  - [(eta(6)-C(10)H(14))RuCl(MU-Cl)](2) (eta(6)-C(10)H(14) = eta(6)-p-cymene) was
      subjected to a bridge-splitting reaction with N,N',N''-triarylguanidines,
      (ArNH)(2)C?NAr, in toluene at ambient temperature to afford [(eta(6)
      C(10)H(14))RuCl{kappa(2)(N,N')((ArN)(2)C-N(H)Ar)}] (Ar = C(6)H(4)Me-4 (1),
      C(6)H(4)(OMe)-2 (2), C(6)H(4)Me-2 (3), and C(6)H(3)Me(2)-2,4 (4)) in high yield
      with a view aimed at understanding the influence of substituent(s) on the aryl
      rings of the guanidine upon the solid-state structure, solution behavior, and
      reactivity pattern of the products. Complexes 1-3 upon reaction with NaN(3) in
      ethanol at ambient temperature afforded [(eta(6)
      C(10)H(14))RuN(3){kappa(2)(N,N')((ArN)(2)C-N(H)Ar)}] (Ar = C(6)H(4)Me-4 (5),
      C(6)H(4)(OMe)-2 (6), and C(6)H(4)Me-2 (7)) in high yield. [3 + 2] cycloaddition
      reaction of 5-7 with RO(O)C-C=C-C(O)OR (R = Et (DEAD) and Me (DMAD))
      (diethylacetylenedicarboxylate, DEAD; dimethylacetylenedicarboxylate, DMAD) in
      CH(2)Cl(2) at ambient temperature afforded [(eta(6)
      C(10)H(14))Ru{N(3)C(2)(C(O)OR)(2)}{kappa(2)(N,N')((ArN)(2)C-N(H)Ar)}].xH(2)O (x =
      1, R = Et, Ar = C(6)H(4)Me-4 (8.H(2)O); x = 0, R = Me, Ar = C(6)H(4)(OMe)-2 (9),
      and C(6)H(4)Me-2 (10)) in moderate yield. The molecular structures of 1-6,
      8.H(2)O, and 10 were determined by single crystal X-ray diffraction data. The
      ruthenium atom in the aforementioned complexes revealed pseudo octahedral "three
      legged piano stool" geometry. The guanidinate ligand in 2, 3, and 6 revealed syn
      syn conformation and that in 4, and 10 revealed syn-anti conformation, and the
      conformational difference was rationalized on the basis of subtle differences in
      the stereochemistry of the coordinated nitrogen atoms caused by the aryl moiety
      in 3 and 4 or steric overload caused by the substituents around the ruthenium
      atom in 10. The bonding pattern of the CN(3) unit of the guanidinate ligand in
      the new complexes was explained by invoking n-pi conjugation involving the
      interaction of the NHAr/N(coord)Ar lone pair with C?Npi* orbital of the imine
      unit. Complexes 1, 2, 5, 6, 8.H(2)O, and 9 were shown to exist as a single isomer
      in solution as revealed by NMR data, and this was ascribed to a fast C-N(H)Ar
      bond rotation caused by a less bulky aryl moiety in these complexes. In contrast,
      3 and 10 were shown to exist as a mixture of three and five isomers in about
      1:1:1 and 1.0:1.2:2.7:3.5:6.9 ratios, respectively in solution as revealed by a
      VT (1)H NMR, (1)H-(1)H COSY in conjunction with DEPT-90 (13)C NMR data measured
      at 233 K in the case of 3. The multiple number of isomers in solution was
      ascribed to the restricted C-N(H)(o-tolyl) bond rotation caused by the bulky o
      tolyl substituent in 3 or the aforementioned restricted C-NH(o-tolyl) bond
      rotation as well as the restricted ruthenium-arene(centroid) bond rotation caused
      by the substituents around the ruthenium atom in 10.

PMID- 22148466
TI  - Sedimentological control on Mn, and other trace elements, in groundwater of the
      Bengal delta.
AB  - To reveal what controls the concentration and distribution of possibly hazardous
      (Mn, U, Se, Cd, Bi, Pb) and nonhazardous (Fe, V, Mo, PO(4)) trace elements in
      groundwater of the Bengal delta, we mapped their concentrations in shallow
      groundwater (<60 mbgl) across 102 km(2) of West Bengal. Only Mn is a potential
      threat to health, with 55% of well water exceeding 0.3 mg/L, the current Indian
      limit for drinking water in the absence of an alternate source, and 75% exceeding
      the desirable limit of 0.1 mg/L. Concentrations of V are <3 MUg/L. Concentrations
      of U, Se, Pb, Ni, Bi, and Cd, are below WHO guideline values.  The distributions
      of Fe, Mn, As, V, Mo, U, PO(4), and delta(18)O in groundwater reflect subsurface
      sedimentology and sources of water. Areas of less negative delta(18)O reveal
      recharge by sources of evaporated water. Concentrations of Fe, As, Mo, and PO(4)
      are high in palaeo-channel groundwaters and low in palaeo-interfluvial
      groundwaters. Concentrations of U, V, and Mn, are low in palaeo-channel
      groundwaters and high in palaeo-interfluvial groundwaters. Concentrations of Fe
      and Mn are highest (18 and 6 mg/L respectively) at dual reduction-fronts that
      form strip interfaces at depth around the edges of palaeo-interfluvial aquifers.
      The fronts form as focused recharge carries dissolved organic carbon into the
      aquifer margins, which comprise brown, iron-oxide bearing, sand. At the Mn
      reduction front, concentrations of V and Mo reach peak concentrations of 3 MUg/L.
      At the Fe-reduction front, concentrations of PO(4) and As reach concentrations 3
      mg/L and 150 MUg/L respectively. Many groundwaters contain >10 mg/L of Cl,
      showing that they are contaminated by Cl of anthropogenic origin and that organic
      matter from in situ sanitation may contribute to driving reduction.

PMID- 22148467
TI  - Confined high-pressure chemical deposition of hydrogenated amorphous silicon.
AB  - Hydrogenated amorphous silicon (a-Si:H) is one of the most technologically
      important semiconductors. The challenge in producing it from SiH(4) precursor is
      to overcome a significant kinetic barrier to decomposition at a low enough
      temperature to allow for hydrogen incorporation into a deposited film. The use of
      high precursor concentrations is one possible means to increase reaction rates at
      low enough temperatures, but in conventional reactors such an approach produces
      large numbers of homogeneously nucleated particles in the gas phase, rather than
      the desired heterogeneous deposition on a surface. We report that deposition in
      confined micro-/nanoreactors overcomes this difficulty, allowing for the use of
      silane concentrations many orders of magnitude higher than conventionally
      employed while still realizing well-developed films. a-Si:H micro-/nanowires can
      be deposited in this way in extreme aspect ratio, small-diameter optical fiber
      capillary templates. The semiconductor materials deposited have ~0.5 atom%
      hydrogen with passivated dangling bonds and good electronic properties. They
      should be suitable for a wide range of photonic and electronic applications such
      as nonlinear optical fibers and solar cells.

PMID- 22148469
TI  - DNA as invisible ink for AFM nanolithography.
AB  - We have used nanografting, an atomic force microscopy (AFM)-based nanolithography
      technique, to fabricate thiolated DNA nanostructures on gold surfaces. The tip
      guided assembly offers opportunities for locally controlling the packing order,
      density, and thus the thickness of the DNA patterns. By selecting proper
      nanografting parameters, we can embed single-stranded DNA (ssDNA) patches into a
      background composed of the same DNA molecule prepared by self-assembly, in which
      the patches remain topographically (and chemically) invisible but have much
      improved packing order. When the complementary DNA (cDNA) is added, the thickness
      of the nanografted layer increases much more dramatically than that of the self
      assembled layer during the hybridization process, and as a result, the pattern
      emerges. Interestingly, the pattern can be reversibly hidden and shown with high
      fidelity simply by dehybridizing and appending the cDNA repeatedly.

PMID- 22148470
TI  - Electrochemically induced reversible and irreversible coupling of triarylamines.
AB  - The electrochemical coupling and dimerization behavior of the low molecular
      compounds triphenylamine (TPA) and 9-phenylcarbazole (PHC) in comparison to tri-p
      tolylamine (p-TTA) with para-blocked methyl groups has been investigated in
      detail. In contrast to the unsubstituted radical cations of TPA and PHC, the
      radical cations of p-TTA are stable in the radical cation state and do not
      undergo any further coupling reactions. However, we found that the dicationic
      state of p-TTA does undergo two different competitive reaction pathways: (1) an
      irreversible intramolecular coupling reaction which leads to phenylcarbazole
      moieties and (2) a reversible intermolecular dimerization leading to charged
      sigma-dimers. The sigma-dimers become decomposed upon discharging at low
      potentials (E(pc) = -0.97 V vs Fc/Fc(+)) so that the starting monomer p-TTA is
      partially regenerated. In particular, the reversible dimerization reaction has
      not been described in literature so far. Polymeric systems containing para-methyl
      blocked triarylamines in the side chain exhibit similar coupling behavior upon
      electrochemical doping.

PMID- 22148468
TI  - A force field with discrete displaceable waters and desolvation entropy for
      hydrated ligand docking.
AB  - In modeling ligand-protein interactions, the representation and role of water are
      of great importance. We introduce a force field and hydration docking method that
      enables the automated prediction of waters mediating the binding of ligands with
      target proteins. The method presumes no prior knowledge of the apo or holo
      protein hydration state and is potentially useful in the process of structure
      based drug discovery. The hydration force field accounts for the entropic and
      enthalpic contributions of discrete waters to ligand binding, improving energy
      estimation accuracy and docking performance. The force field has been calibrated
      and validated on a total of 417 complexes (197 training set; 220 test set), then
      tested in cross-docking experiments, for a total of 1649 ligand-protein complexes
      evaluated. The method is computationally efficient and was used to model up to 35
      waters during docking. The method was implemented and tested using unaltered
      AutoDock4 with new force field tables.

PMID- 22148471
TI  - Identification of 3,N(4)-etheno-5-methyl-2'-deoxycytidine in human DNA: a new
      modified nucleoside which may perturb genome methylation.
AB  - Methylation of cytidine at dCpdG sequences regulates gene expression and is
      altered in many chronic inflammatory diseases. Inflammation generates lipid
      peroxidation (LPO) products which can react with deoxycytidine, deoxyadenosine,
      and deoxyguanosine in DNA to form pro-mutagenic exocyclic etheno-nucleoside
      residues. Since 5-methyl-2'-deoxycytidine (5mdC) residues exhibit increased
      nucleophilicity at N3, they should be even better targets for LPO products. We
      synthesized and characterized 3,N(4)-etheno-5-methyl-2'-deoxycytidine-3'
      phosphate and showed that LPO products can indeed form the corresponding etheno
      5mdC (epsilon5mdC) lesion in DNA in vitro. Our newly developed (32)P-postlabeling
      method was subsequently used to detect epsilon5mdC lesions in DNA from human
      white blood cells, lung, and liver at concentrations 4-10 times higher than that
      observed for etheno adducts on nonmethylated cytidine. Our new detection method
      can now be used to explore the hypothesis that this DNA lesion perturbs the DNA
      methylation status.

PMID- 22148473
TI  - Electronic structure and conformation properties of halogen-substituted acetyl
      acrylic anhydrides, CX3C(O)OC(O)CH?CH2 (X = H, F, or Cl).
AB  - Acetyl acrylic anhydride (CH(3)C(O)OC(O)CHCH(2)) and its halogen-substituted
      derivatives (CF(3)C(O)OC(O)CHCH(2) and CCl(3)C(O)OC(O)CHCH(2)) were prepared by
      the heterogeneous reaction of gaseous CH(2)?CHC(O)Cl with CX(3)C(O)OAg (X = H, F,
      or Cl). The molecular conformations and electronic structure of these three
      compounds were investigated by HeI photoelectron spectroscopy, photoionization
      mass spectroscopy, FT-IR, and theoretical calculations. They were theoretically
      predicted to prefer the [ss-c] conformation, with each C?O bond syn with respect
      to the opposite O-C bond and the C?C bond in cis orientation to the adjacent C?O
      bond. The experimental first vertical ionization potential for
      CH(3)C(O)OC(O)CHCH(2), CF(3)C(O)OC(O)CHCH(2), and CCl(3)C(O)OC(O)CHCH(2) was
      determined to be 10.91, 11.42, and 11.07 eV, respectively. In this study, the
      rule of the conformation properties of anhydride XC(O)OC(O)Y was improved by
      analyzing the different conformations of anhydrides with various substitutes.

PMID- 22148472
TI  - Structural and biochemical characterization of linear dinucleotide analogues
      bound to the c-di-GMP-I aptamer.
AB  - The cyclic dinucleotide c-di-GMP regulates lifestyle transitions in many
      bacteria, such as the change from a free motile state to a biofilm-forming
      community. Riboswitches that bind this second messenger are important downstream
      targets in this bacterial signaling pathway. The breakdown of c-di-GMP in the
      cell is accomplished enzymatically and results in the linear dinucleotide pGpG.
      The c-di-GMP-binding riboswitches must be able to discriminate between their
      cognate cyclic ligand and linear dinucleotides in order to be selective
      biological switches. It has been reported that the c-di-GMP-I riboswitch binds c
      di-GMP 5 orders of magnitude better than the linear pGpG, but the cause of this
      large energetic difference in binding is unknown. Here we report binding data and
      crystal structures of several linear c-di-GMP analogues in complex with the c-di
      GMP-I riboswitch. These data reveal the parameters for phosphate recognition and
      the structural basis of linear dinucleotide binding to the riboswitch.
      Additionally, the pH dependence of binding shows that exclusion of pGpG is not
      due to the additional negative charge on the ligand. These data reveal principles
      that, along with published work, will contribute to the design of c-di-GMP
      analogues with properties desirable for use as chemical tools and potential
      therapeutics.

PMID- 22148474
TI  - Liquid chromatography-tandem mass spectrometry for the determination of
      sphingomyelin species from calf brain, ox liver, egg yolk, and krill oil.
AB  - In this study, molecular species of sphingomyelin (SM) in egg yolk, calf brain,
      ox liver, and krill oil were investigated. Classes of phospholipids (PLs) were
      purified, identified, and quantified by normal phase semipreparative high
      performance liquid chromatography (HPLC) combined with evaporative light
      scattering detectors (ELSD). For SM molecular species identification, pure SM
      collected through a flow splitter was loaded to HPLC-electrospray ionization
      tandem mass spectrometry (LC-ESI-MS(2)), with 100% methanol containing 5 mM
      ammonium formate as mobile phase. In addition to classes of PLs, the used
      approach allowed the determination of profiles of SM species in egg yolk, ox
      liver, and calf brain, whereas krill oil turned out not to contain any SM. It
      also allowed the separation and identification of SM subclasses, as well as
      tentative identification of species with the same molecular mass, including
      isomers. The results showed that egg yolk contained the highest proportion of
      (d18:1-16:0)SM (94.1%). The major SM molecular species in ox liver were (d18:1
      16:0)SM (25.5%), (d18:1-23:0)SM (19.7%), (d18:1-24:0)SM (13.2%), and (d18:1
      22:0)SM (12.5%). Calf brain SM was rich in species such as (d18:1-18:0)SM
      (40.7%), (d18:1-24:1)SM (17.1%), and (d18:1-20:0)SM (10.8%).

PMID- 22148475
TI  - Reversal of multidrug resistance by morning glory resin glycosides in human
      breast cancer cells.
AB  - Reversal of multidrug resistance (MDR) by thirty resin glycosides from the
      morning glory family (Convolvulaceae) was evaluated in vinblastine-resistant
      human breast carcinoma cells (MCF-7/Vin). The effects of these amphipathic
      compounds on the cytotoxicity and P-glycoprotein (P-gp)-mediated MDR were
      estimated with the sulforhodamine B colorimetric assay. Active noncytotoxic
      compounds exerted a potentiation effect of vinblastine susceptibility by 1- to
      over 1906-fold at tested concentrations of 5 and 25 MUg/mL. Murucoidin V (1)
      enhanced vinblastine activity 255-fold when incorporated at 25 MUg/mL and also,
      based on flow cytometry, significantly increased the intracellular accumulation
      of rhodamine 123 with the use of reserpine as a positive control for a MDR
      reversal agent. Incubation of MCF-7/Vin cells with 1 caused an increase in uptake
      and notably lowered the efflux rate of rhodamine 123. Decreased expression of P
      glycoprotein by compound 1 was detected by immunofluorescence flow cytometry
      after incubation with an anti-P-gp monoclonal antibody. These results suggest
      that resin glycosides represent potential efflux pump inhibitors for overcoming
      MDR in cancer therapy.

PMID- 22148478
TI  - Environmental currents.

PMID- 22148477
TI  - Editorial - environmental facts obscure the truth.

PMID- 22148479
TI  - Outlook - fly ash AIDS in sludge disposal.

PMID- 22148481
TI  - OWRR Covers the Waterfront.

PMID- 22148480
TI  - Industry has an Important Role in Development of Water Quality Programs.

PMID- 22148482
TI  - AMA Convenes Congress on Environmental Health Management.

PMID- 22148483
TI  - The continuing tale of the torrey canyon.

PMID- 22148484
TI  - "We enter the age of environmental quality".

PMID- 22148486
TI  - The Federal Resources Research Program - All Quality Criteria for Sulfur Oxides
      Set By HEW.

PMID- 22148485
TI  - Power systems for electric vehicles.

PMID- 22148487
TI  - Prediction of nitrification effects of the dissolved oxygen balance of streams.

PMID- 22148489
TI  - Preconcentration for trace analysis of sea waters.

PMID- 22148488
TI  - Identification of a cholinesterase-inhibiting compound from an industrial
      effluent.

PMID- 22148490
TI  - Nutrient budget: rational analysis of eutrophication in a Connecticut lake.

PMID- 22148491
TI  - Earthy-smelling substance from a blue-green alga.

PMID- 22148493
TI  - Infrared analysis of gases: a new method.

PMID- 22148492
TI  - Microdetermination of  peroxides by kinetic colorimetry.

PMID- 22148494
TI  - New products digest.

PMID- 22148495
TI  - New literature digest.

PMID- 22148496
TI  - Bookshelf - an ecological handbook:  a gaggle of facts.

PMID- 22148498
TI  - Letters - more on lake erie.

PMID- 22148497
TI  - Letters - foam separation - an additional look.

PMID- 22148499
TI  - Selective oxidation of unsaturated alcohols catalyzed by sodium nitrite and 2,3
      dichloro-5,6-dicyano-1,4-benzoquinone with molecular oxygen under mild
      conditions.
AB  - We have developed a simple and practical process for the oxidation of alcohols to
      the corresponding carbonyl compounds by using a low catalytic amount of DDQ,
      NaNO(2) as a cocatalyst, and molecular oxygen as terminal oxidant. Nitric oxide
      generated in situ by NaNO(2) in the presence of AcOH is essential for the
      realization of the catalytic cycle at room temperature. The practical utility of
      this catalytic process has been demonstrated in the gram-scale oxidation of
      cinnamyl alcohol.

PMID- 22148500
TI  - Bioconjugate of lysozyme and the antibacterial marine sesquiterpene quinone
      avarone and its derivatives.
AB  - A conjugate of lysozyme with avarone, a bioactive sesquiterpene quinone of marine
      origin, and its three derivatives were synthesized. MALDI TOF mass spectral
      analysis and tryptic digestion showed that the only residue in lysozyme that was
      modified by all derivatives was lysine 97. The identity of the residue was in
      full correlation with the prediction obtained by molecular modeling. All
      bioconjugates preserved most of the enzymatic activity of lysozyme. The melting
      point of the conjugates was slightly increased in comparison to lysozyme,
      indicating a slight stabilization of structure. The antibacterial activity of all
      the conjugates to both Gram positive and Gram negative bacteria was stronger than
      the activity of either lysozyme or the quinones, the MIC values being in low
      micromolar range for some conjugates.

PMID- 22148501
TI  - Fabrication of graphene oxide nanosheets incorporated monolithic column via one
      step room temperature polymerization for capillary electrochromatography.
AB  - Graphene oxide (GO) has received great interest for its unique properties and
      potential diverse applications. Here, we show the fabrication of GO nanosheets
      incorporated monolithic column via one-step room temperature polymerization for
      capillary electrochromatography (CEC). GO is attractive as the stationary phase
      for CEC because it provides not only ionized oxygen-containing functional groups
      to modify electroendoosmotic flow (EOF) but also aromatic macromolecule to give
      hydrophobicity and pi-pi electrostatic stacking property. Incorporation of GO
      into monolithic column greatly increased the interactions between the tested
      neutral analytes (alkyl benzenes and polycyclic aromatics) and the stationary
      phase and significantly improved their CEC separation. Baseline separation of the
      tested neutral analytes on the GO incorporated monolithic column was achieved on
      the basis of typical reversed-phase separation mechanism. The precision (relative
      standard deviation (RSD), n = 3) of EOF was 0.3%, while the precision of
      retention time, peak area, and peak height for the tested neutral analytes were
      in the range of 0.4-3.0%, 0.8-4.0%, and 0.8-4.9%, respectively. In addition, a
      set of anilines were well separated on the GO incorporated monolith. The GO
      incorporated monolithic columns are promising for CEC separation.

PMID- 22148502
TI  - Photonic-plasmonic mode coupling in on-chip integrated optoplasmonic molecules.
AB  - We investigate photonic-plasmonic mode coupling in a new class of optoplasmonic
      materials that comprise dielectric microspheres and noble metal nanostructures in
      a morphologically well-defined on-chip platform. Discrete networks of
      optoplasmonic elements, referred to as optoplasmonic molecules, were generated
      through a combination of top-down fabrication and template-guided self-assembly.
      This approach facilitated a precise and controllable vertical and horizontal
      positioning of the plasmonic elements relative to the whispering gallery mode
      (WGM) microspheres. The plasmonic nanostructures were positioned in or close to
      the equatorial plane of the dielectric microspheres where the fields associated
      with the plasmonic modes can synergistically interact with the evanescent fields
      of the WGMs. We characterized the far-field scattering spectra of discrete
      optoplasmonic molecules that comprised two coupled 2.048 MUm diameter polystyrene
      microspheres each encircled by four 148 nm diameter Au nanoparticles (NPs),
      through far-field scattering spectroscopy. We observed a broadening of the TE and
      TM modes in the scattering spectra of the optoplasmonic dimers indicative of an
      efficient photonic-plasmonic mode coupling between the coupled photonic modes of
      the WGM resonators and the localized surface plasmon modes of the NPs. Our
      experimental findings are supported by generalized multiple particle Mie theory
      simulations, which provide additional information about the spatial distributions
      of the near fields associated with the photonic-plasmonic hybrid modes in the
      investigated optoplasmonic molecules. The simulations reveal partial localization
      of the spectrally sharp hybrid modes outside of the WGM microspheres on the Au
      NPs where the local E-field intensity is enhanced by approximately 2 orders of
      magnitude over that of an individual Au NP.

PMID- 22148503
TI  - Single fluorescent probe responds to H2O2, NO, and H2O2/NO with three different
      sets of fluorescence signals.
AB  - Hydrogen peroxide (H(2)O(2)) acts as a signaling molecule in a wide variety of
      signaling transduction processes and an oxidative stress marker in aging and
      disease. However, excessive H(2)O(2) production is implicated with various
      diseases. Nitric oxide (NO) serves as a secondary messenger inducing vascular
      smooth muscle relaxation. However, mis-regulation of NO production is associated
      with various disorders. To disentangle the complicated inter-relationship between
      H(2)O(2) and NO in the signal transduction and oxidative pathways, fluorescent
      reporters that are able to display distinct signals to H(2)O(2), NO, and
      H(2)O(2)/NO are highly valuable. Herein, we present the rational design,
      synthesis, spectral properties, and living cell imaging studies of FP-H(2)O(2)
      NO, the first single-fluorescent molecule, that can respond to H(2)O(2), NO, and
      H(2)O(2)/NO with three different sets of fluorescence signals. FP-H(2)O(2)-NO
      senses H(2)O(2), NO, and H(2)O(2)/NO with a fluorescence signal pattern of blue
      black-black, black-black-red, and black-red-red, respectively. Significantly, we
      have further demonstrated that FP-H(2)O(2)-NO, a single fluorescent probe, is
      capable of simultaneously monitoring endogenously produced NO and H(2)O(2) in
      living macrophage cells in multicolor imaging. We envision that FP-H(2)O(2)-NO
      will be a unique molecular tool to investigate the interplaying roles of H(2)O(2)
      and NO in the complex interaction networks of the signal transduction and
      oxidative pathways. In addition, this work establishes a robust strategy for
      monitoring the multiple ROS and RNS species (H(2)O(2), NO, and H(2)O(2)/NO) using
      a single fluorescent probe, and the modularity of the strategy may allow it to be
      extended for other types of biomolecules.

PMID- 22148504
TI  - Controlling number of indene solubilizing groups in multiadduct fullerenes for
      tuning optoelectronic properties and open-circuit voltage in organic solar cells.
AB  - The ability to tune the lowest unoccupied molecular orbital (LUMO)/highest
      occupied molecular orbital (HOMO) levels of fullerene derivatives used as
      electron acceptors is crucial in controlling the optical/electrochemical
      properties of these materials and the open circuit voltage (V(oc)) of solar
      cells. Here, we report a series of indene fullerene multiadducts (ICMA, ICBA, and
      ICTA) in which different numbers of indene solubilizing groups are attached to
      the fullerene molecule. The addition of indene units to fullerene raised its LUMO
      and HOMO levels, resulting in higher V(oc) values in the photovoltaic device.
      Bulk-heterojunction (BHJ) solar cells fabricated from poly(3-hexylthiophene)
      (P3HT) and a series of fullerene multiadducts-ICMA, ICBA, and ICTA showed V(oc)
      values of 0.65, 0.83, and 0.92 V, respectively. Despite demonstrating the highest
      V(oc) value, the P3HT:ICTA device exhibited lower efficiency (1.56%) than the
      P3HT:ICBA device (5.26%) because of its lower fill factor and current. This
      result could be explained by the lower light absorption and electron mobility of
      the P3HT:ICTA device, suggesting that there is an optimal number of the
      solubilizing group that can be added to the fullerene molecule. The effects of
      the addition of solubilizing groups on the optoelectrical properties of fullerene
      derivatives were carefully investigated to elucidate the molecular structure
      device function relationship.

PMID- 22148506
TI  - Tuning the excitonic and plasmonic properties of copper chalcogenide
      nanocrystals.
AB  - The optical properties of stoichiometric copper chalcogenide nanocrystals (NCs)
      are characterized by strong interband transitions in the blue part of the
      spectral range and a weaker absorption onset up to ~1000 nm, with negligible
      absorption in the near-infrared (NIR). Oxygen exposure leads to a gradual
      transformation of stoichiometric copper chalcogenide NCs (namely, Cu(2-x)S and
      Cu(2-x)Se, x = 0) into their nonstoichiometric counterparts (Cu(2-x)S and Cu(2
      x)Se, x > 0), entailing the appearance and evolution of an intense localized
      surface plasmon (LSP) band in the NIR. We also show that well-defined copper
      telluride NCs (Cu(2-x)Te, x > 0) display a NIR LSP, in analogy to
      nonstoichiometric copper sulfide and selenide NCs. The LSP band in copper
      chalcogenide NCs can be tuned by actively controlling their degree of copper
      deficiency via oxidation and reduction experiments. We show that this controlled
      LSP tuning affects the excitonic transitions in the NCs, resulting in
      photoluminescence (PL) quenching upon oxidation and PL recovery upon subsequent
      reduction. Time-resolved PL spectroscopy reveals a decrease in exciton lifetime
      correlated to the PL quenching upon LSP evolution. Finally, we report on the
      dynamics of LSPs in nonstoichiometric copper chalcogenide NCs. Through pump-probe
      experiments, we determined the time constants for carrier-phonon scattering
      involved in LSP cooling. Our results demonstrate that copper chalcogenide NCs
      offer the unique property of holding excitons and highly tunable LSPs on demand,
      and hence they are envisaged as a unique platform for the evaluation of
      exciton/LSP interactions.

PMID- 22148505
TI  - Characterization of the redox activity and disulfide bond formation in
      apurinic/apyrimidinic endonuclease.
AB  - Apurinic/apyrimidinic endonuclease (APE1) is an unusual nuclear redox factor in
      which the redox-active cysteines identified to date, C65 and C93, are surface
      inaccessible residues whose activities may be influenced by partial unfolding of
      APE1. To assess the role of the five remaining cysteines in APE1's redox
      activity, double-cysteine mutants were analyzed, excluding C65A, which is redox
      inactive as a single mutant. C93A/C99A APE1 was found to be redox-inactive,
      whereas other double-cysteine mutants retained the same redox activity as that
      observed for C93A APE1. To determine whether these three cysteines, C65, C93, and
      C99, were sufficient for redox activity, all other cysteines were substituted
      with alanine, and this protein was shown to be fully redox-active. Mutants with
      impaired redox activity failed to stimulate cell proliferation, establishing an
      important role for APE1's redox activity in cell growth. Disulfide bond formation
      upon oxidation of APE1 was analyzed by proteolysis of the protein followed by
      mass spectrometry analysis. Within 5 min of exposure to hydrogen peroxide, a
      single disulfide bond formed between C65 and C138 followed by the formation of
      three additional disulfide bonds within 15 min; 10 total disulfide bonds formed
      within 1 h. A single mixed-disulfide bond involving C99 of APE1 was observed for
      the reaction of oxidized APE1 with thioredoxin (TRX). Disulfide-bonded APE1 or
      APE1-TRX species were further characterized by size exclusion chromatography and
      found to form large complexes. Taken together, our data suggest that APE1 is a
      unique redox factor with properties distinct from those of other redox factors.

PMID- 22148508
TI  - Unusual nonoctahedral geometry with molybdenum oxoimido complexes containing eta2
      pyrazolate ligands.
AB  - The preparation and oxygen-atom-transfer (OAT) reactivity of oxoimido complexes
      [MoO(N-t-Bu)(t-Bu(2)-4-Rpz)(2)] [where R = H (1), Br (2), and Me (3); t-Bu(2)pz =
      3,5-di-tert-butylpyrazolate] are reported. The reaction of the potassium salt of
      the respective pyrazolate ligands and the molybdenum oxoimido precursor, [MoO(N-t
      Bu)Cl(2)(dme)] (dme = dimethoxyethane), in toluene afforded complexes 1-3 in good
      yields. The complexes were fully characterized by (1)H and (13)C NMR and IR
      spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray
      crystallography. The solid-state structures reveal that, in each case, the
      molybdenum center is coordinated by one oxo, one N-t-Bu group, and two sterically
      demanding pyrazolate ligands via their two adjacent nitrogen atoms in an eta(2)
      fashion. Coordination around the metal center is severely distorted from
      octahedral and might be seen as closely approaching a distorted trigonal
      prismatic geometry, which is relevant to the active site of dimethyl sulfoxide
      reductase in its oxidized form. The potential utility of all of the complexes 1-3
      for OAT reactivity toward PMe(3) at room temperature is examined, and plausible
      mechanistic pathways are explored by density functional theory calculations.
      Furthermore, the complexes reported here open a new and convenient entry into
      mixed oxoimidomolybdenum complexes.

PMID- 22148509
TI  - Relation between electron scattering resonances of isolated NTCDA molecules and
      maxima in the density of unoccupied states of condensed NTCDA layers.
AB  - The empty-level structure of the 1,4,5,8-naphthalenetetracarboxylic dianhydride
      (NTCDA) molecule is characterized by means of dissociative electron attachment
      (DEA) experiments in the gas phase coupled with DFT calculations. Distinct maxima
      in the anion currents generated by electron attachment to NTCDA, as a function of
      incident electron energy, are ascribed to capture of incident electrons into
      empty orbitals, i.e., the process referred to as shape resonance. The empty
      orbital energies of gas-phase NTCDA shifted to 1.2 eV lower energy reproduce
      satisfactorily the maxima of the unoccupied electronic states of a multilayer
      NTCDA film measured by means of the very low energy electron diffraction method
      and the total current spectroscopy measurement scheme. The present results
      indicate that the empty levels of individual NTCDA molecules are stabilized in
      the solid state, but their relative energies remain nearly unaltered. The
      stabilization energy in multilayer film of NTCDA molecules is likely due to
      attractive polarization forces. Fragmentation of the gas-phase NTCDA temporary
      parent anions via the DEA mechanism, the other issue of the present
      investigation, leads to the rupture of the bonds between the end carbonyl groups
      and the naphthalene core, and occurs at incident electron energies above 2 eV.
      Possible chemical changes in condensed NTCDA molecules initiated by the DEA
      mechanism under conditions of electron transport through the film are discussed.

PMID- 22148510
TI  - Reaction of InCl3 with various reducing agents: InCl3-NaBH4-mediated reduction of
      aromatic and aliphatic nitriles to primary amines.
AB  - While alternative methods of preparing dichloroindium hydride (HInCl(2)) via the
      in situ reduction of InCl(3) using lithium amino borohydride (LAB) were explored,
      generation of HInCl(2) from the reduction of InCl(3) by sodium borohydride
      (NaBH(4)) was also re-evaluated for comparison. The reductive capability of the
      InCl(3)/NaBH(4) system was found to be highly dependent on the solvent used.
      Investigation by (11)B NMR spectroscopic analyses indicated that the reaction of
      InCl(3) with NaBH(4) in THF generates HInCl(2) along with borane-tetrahydrofuran
      (BH(3).THF) in situ. Nitriles underwent reduction to primary amines under
      optimized conditions at 25  degrees C using 1 equiv of anhydrous InCl(3) with 3
      equiv of NaBH(4) in THF. A variety of aromatic, heteroaromatic, and aliphatic
      nitriles were reduced to their corresponding primary amine in 70-99% isolated
      yields. Alkyl halide and nitrile functional groups were reduced in tandem by
      utilizing the reductive capabilities of both HInCl(2) and BH(3).THF in a one-pot
      reaction. Finally, the selective reduction of the carbon bromine bond in the
      presence of nitriles was achieved by generating HInCl(2) via the reduction
      InCl(3) with NaBH(4) in CH(3)CN or with lithium dimethylaminoborohydride (MeLAB)
      in THF.

PMID- 22148511
TI  - Handling of tautomerism and stereochemistry in compound registration.
AB  - Automated registration of compounds from external sources is necessitated by the
      numerous compound acquisitions from vendors and by the increasing number of
      collaborations with external partners. A prerequisite for automating compound
      registration is a robust module for determining the structural novelty of the
      input structures. Any such tool needs to be able to take uncertainty about
      stereochemistry into account and to identify tautomeric forms of the same
      compound. It also needs to validate structures for potential mistakes in
      connectivity and stereochemistry. Genentech has implemented a Structure
      Normalization Module based on toolkits offered by OpenEye Scientific Software.
      The module is incorporated in a graphical application for single compound
      registration and in scripts for bulk registration. It is also used for checking
      compounds submitted by our collaborators via partner-specific Internet sites. The
      Genentech Structure Normalization Module employs the widely used V2000 molfile
      format to accommodate structures received from a wide variety of sources. To
      determine how much information is known about the stereochemistry of each
      compound, the module requires a separate stereochemical assignment. A structural
      uniqueness check is performed by comparing the canonical SMILES of a standard
      tautomer. This paper offers a discussion of the steps taken to validate the
      chemical structure and generate the canonical SMILES of the standard tautomer. It
      also describes the integration of the validation module in compound registration
      pathways.

PMID- 22148512
TI  - Biopolymers from vegetable oils via catalyst- and solvent-free "click" chemistry:
      effects of cross-linking density.
AB  - New monomers were prepared by introducing the azide groups in castor, canola,
      corn, soybean, and linseed oils. Polymerization of the azidated oils with
      alkynated soybean oil under thermal "click" chemistry conditions (without using a
      solvent or a catalyst) yielded fully cross-linked elastomers (1-5) of almost the
      same density (1.05 * 10(-3) kg/m(3)). The degree of cross-linking gradually
      increased from the castor-derived polymer (220 mol/m(3)) to the linseed-derived
      polymer (683 mol/m(3)). A systematic correlation between the degree of cross
      linking and the thermal and mechanical properties was observed in these
      biopolymers. Tensile strength (0.62-3.39 MPa) and glass transition temperature (
      5 to 16  degrees C) increased and the linear thermal expansion coefficient
      decreased in the series from the canola-derived polymer (2) to the linseed
      derived polymer (5). The castor-derived polymer (1) that possesses an additional
      hydroxyl group per fatty acid chain behaved differently.

PMID- 22148513
TI  - High-resolution, continuous method for measurement of acidity in ice cores.
AB  - The acid content of ice core samples provides information regarding the history
      of volcanism, biogenic activity, windblown dust, forest fires, and pollution
      induced acid rain. A continuous ice core analysis allows for collection of high
      resolution data in a very efficient manner, but this technique has not been
      readily applied to the measurement of pH and acidity in ice cores. The difficulty
      arises because the sample is highly undersaturated with respect to carbon dioxide
      (CO(2)) immediately after melting, making it difficult to maintain stable
      concentrations of dissolved carbon dioxide and carbonic acid (H(2)CO(3)). Here,
      we present a solution to this problem in the form of a small flow-through
      bubbling chamber that is supplied with a known concentration of CO(2). The
      bubbling action allows for quick equilibration while the small size of the
      chamber limits sample mixing in order to maintain high resolution. Thorough error
      analysis provides a measurement uncertainty of +/-0.20 MUM or +/-5% of the
      acidity value, whichever is greater, and the T95 signal response time is
      determined to be 1.25 min. The performance of the technique is further evaluated
      with data from a 63-year ice core from northwest Greenland for which all major
      ion species were also measured. The measured acidity closely matches the acidity
      derived from a charge balance calculation, indicating that all of the analytes
      were measured accurately. The performance specifications that we provide are
      applicable to ice cores with low concentrations of alkaline dust (<500 ppb),
      which includes the vast majority of ice cores that are collected. To date, the
      method has not been evaluated with samples containing high alkaline dust
      concentrations, such as Greenland cores from the last glacial period, where
      measurement could be made difficult by memory effects as particles coat the
      internal surfaces of the sample stream.

PMID- 22148514
TI  - Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6
      deoxytetracycline: a potent, broad spectrum antibacterial agent.
AB  - This and the accompanying report (DOI: 10.1021/jm201467r ) describe the design,
      synthesis, and evaluation of a new generation of tetracycline antibacterial
      agents, 7-fluoro-9-substituted-6-demethyl-6-deoxytetracyclines
      ("fluorocyclines"), accessible through a recently developed total synthesis
      approach. These fluorocyclines possess potent antibacterial activities against
      multidrug resistant (MDR) Gram-positive and Gram-negative pathogens. One of the
      fluorocyclines, 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline
      (17j, also known as TP-434, 50th Interscience Conference on Antimicrobial Agents
      and Chemotherapy Conference , Boston, MA , September 12-15, 2010 , poster F1 -
      2157 ), is currently undergoing phase 2 clinical trials in patients with
      complicated intra-abdominal infections (cIAI).

PMID- 22148515
TI  - Combinatorial library of lipidoids for in vitro DNA delivery.
AB  - A combinatorial library of lipidoids was constructed and studied for in vitro
      gene delivery. The library of lipidoids was synthesized by reacting commercially
      available amines with lipophilic acrylates, acrylamides, or epoxides. Lipidoids
      derived from amine 86 (N,N-bis(2-hydroxyethyl)ethylene diamine) and amine 87 (N
      (3-aminopropyl)diethaneamine) showed high efficiency in DNA delivery, some with a
      higher transfection efficiency than Lipofectamine 2000, a commonly used
      commercial gold standard for in vitro gene delivery. The structure-activity
      relationship between the lipidoids was further studied with respect to small
      variations in chemical structures and the resulting efficiency in DNA delivery in
      vitro. Since these lipidoids are easy to synthesize and do not require a colipid
      for efficient DNA delivery, they could offer an inexpensive but effective
      alternative to other commonly used commercial gene delivery carriers.

PMID- 22148517
TI  - Short cold storage enhances the anthocyanin contents and level of transcripts
      related to their biosynthesis in blood oranges.
AB  - The health benefits associated with the consumption of anthocyanin-containing
      foods are extensively documented. Mature fruits of blood oranges and their
      hybrids are characterized by the presence of these bioactive pigments, the
      abundance of which can be enhanced by storing fruit at cooling nonfreezing
      temperature. In this work the effects of short low-temperature exposure (4 
      degrees C * 15 days) upon orange anthocyanin content and the expression of
      structural genes belonging to the pigment biosynthesis pathway were investigated.
      The results highlight that anthocyanin levels of fruit exposed to cold sharply
      increase, reaching, after 6 days of storage, a value 8 times higher than that
      observed in the time zero samples, thus suggesting that fruit with enhanced
      health-related attributes might be obtained at this storage stage. The analysis
      of gene expression shows that the amount of transcripts of all considered genes
      (CM1, PAL, CHS, DFR, ANS, UFGT, and GST) sharply increased after 3-6 days of cold
      storage, confirming previous data showing that the biosynthesis of anthocyanins
      is a cold-regulated pathway. By comparing the expression of selected genes (PAL,
      DFR, and UFGT) between blood and common oranges, it turns out that those genes
      strictly involved in anthocyanin biosynthesis are not cold responsive in common
      oranges. Moreover, the data highlight that the EST encoding the transcription
      factor NAC domain protein is selectively induced by cold in blood oranges but not
      in common oranges, thus proposing it as a candidate gene specifically involved in
      blood orange response to cold exposure.

PMID- 22148519
TI  - Carbon nanotube nanoweb-bioelectrode for highly selective dopamine sensing.
AB  - A highly sensitive and selective dopamine sensor was fabricated with the unique
      3D carbon nanotube nanoweb (CNT-N) electrode. The as-synthesised CNT-N was
      modified by oxygen plasma to graft functional groups in order to increase
      selective electroactive sites at the CNT sidewalls. This electrode was
      characterized physically and electrochemically using HRSEM, Raman, FT-IR, and
      cyclic voltammetry (CV). Our investigations indicated that the O(2)-plasma
      treated CNT-N electrode could serve as a highly sensitive biosensor for the
      selective sensing of dopamine (DA, 1 MUM to 20 MUM) in the presence of ascorbic
      acid (AA, 1000 MUM).

PMID- 22148518
TI  - Differentiation of prostate cancer cells using flexible fluorescent polymers.
AB  - Using water-soluble, fluorescent, flexible polymers, we have devised a novel
      methodology for identification and differentiation of prostate cancer cells.
      Using a stepwise linear discriminant analysis, we demonstrate that the
      differential modulations of the polymer emission intensities in the presence of
      conditioned cell culture media can be used to distinguish between prostate cancer
      subtypes and between cancerous and noncancer cells. The differences in the
      compositions of the conditioned cell culture media are likely contributing to
      different fluorescence spectral patterns of the polymers. This in vitro approach
      may provide a novel platform for the development of an alternative prostate
      cancer diagnostic and subtyping technique.

PMID- 22148520
TI  - Dual luminescent tetranuclear organogold(I) macrocycles of 5,5'-diethynyl-2,2'
      bipyridine and their efficient sensitization of Yb(III) luminescence.
AB  - Reaction of (AuC=CbpyC=CAu)(n) (HC=CbpyC=CH = 5,5'-diethynyl-2,2'-bipyridine)
      with diphosphine ligands Ph(2)P(CH(2))(n)PPh(2) (n = 1 dppm, 3 dppp, 5 dpppen, 6
      dpph), 1,1'-bis(diphenylphosphino)ferrocene (dppf), and 1,2
      bis(diphenylphosphino)benzene (bdpp) in CH(2)Cl(2) afforded the corresponding
      dual luminescent gold(I) complexes [(AuC=CbpyC=CAu)(2)(MU-dppm)(2)] (1),
      [(AuC=CbpyC=CAu)(2)(MU-dppp)(2)] (2), [(AuC=CbpyC=CAu)(2)(MU-dpppen)(2)] (3),
      [(AuC=CbpyC=CAu)(2)(MU-dpph)(2)] (4), [(AuC=CbpyC=CAu)(2)(MU-dppf)(2)] (5), and
      [(AuC=CbpyC=CAu)(2)(MU-bdpp)(2)] (6). The solid structures of complexes 1 and 2
      are confirmed to be tetranuclear macrocyclic rings by single crystal structure
      analysis, and those of complexes 3-6 are proposed to be similar to those of
      complexes 1 and 2 in structure because their good solubility in CH(2)Cl(2), their
      HRMS results, and the P...P separations of 20.405-20.697 A in the same linear
      rigid P-Au-C=CbpyC=C-Au-P unit are all favorable to form such 2:4:2 macrocycles.
      Each of the absorption spectral titrations between complexes 1-6 and
      Yb(hfac)(3)(H(2)O)(2) (Hhfac = hexafluoroacetylacetone) gives a 2:1 ratio between
      the Yb(hfac)(3) unit and the complex 1-6 moieties. The energy transfer occurs
      efficiently from the gold(I) alkynyl antennas 1-6 to Yb(III) centers with the
      donor ability in the order of 1 ~ 2 ~ 3 ~ 4 > 6 > 5.

PMID- 22148521
TI  - Parallel beta-sheet secondary structure is stabilized and terminated by
      interstrand disulfide cross-linking.
AB  - Disulfide bonds between Cys residues in adjacent strands of parallel beta-sheets
      are rare among proteins, which suggests that parallel beta-sheet structure is not
      stabilized by such disulfide cross-links. We report experimental results that
      show, surprisingly, that an interstrand disulfide bond can stabilize parallel
      beta-sheets formed by an autonomously folding peptide in aqueous solution. NMR
      analysis reveals that parallel beta-sheet structure is terminated beyond the
      disulfide bond, which causes deviation from the extended backbone conformation at
      one of the Cys residues.

PMID- 22148524
TI  - Editorial - pollution control should proceed from a sound base.

PMID- 22148522
TI  - A new route toward ultrasensitive, flexible chemical sensors: metal nanotubes by
      wet-chemical synthesis along sacrificial nanowire templates.
AB  - We developed a novel low-temperature, wet-chemical process for the facile
      synthesis of metal nanotube arrays through the reduction of metal precursors
      along sacrificial metal oxide nanowire templates and demonstrated its
      applications to the ultrasensitive, low-power, mechanically robust, and flexible
      chemical sensors. The in situ dissolution of ZnO nanowire templates, which were
      hydrothermally grown on electrode surfaces, during the reaction allows the direct
      formation of tubular Pd nanostructures on the sensor devices without the need of
      complex processes for device integration or template removal. Moreover, this
      simple synthesis was carried out at low-temperature with mild chemical
      conditions; therefore we could make Pd nanotube devices not only on silicon
      substrates but also on flexible polymer substrates. The H(2) sensing of such Pd
      nanotube devices was investigated under various mechanical loading and showed
      excellent reliability and robustness. The sensitivity of our devices was found to
      be at least 2 orders of magnitude higher than literature values for H(2) sensors,
      which can be attributed to the high surface area and the well-formed interconnect
      of Pd tubular nanostructures in our devices.

PMID- 22148525
TI  - Environmental currents.

PMID- 22148526
TI  - Urban problems met in environmental centers.

PMID- 22148527
TI  - Outlook.

PMID- 22148529
TI  - California's Auto Smog Cauldron Continues to Bubble.

PMID- 22148528
TI  - New data system designed for marine chemical data.

PMID- 22148531
TI  - The sinister side effects of science.

PMID- 22148530
TI  - Achema 67.

PMID- 22148532
TI  - Quote - run the system as a whole.

PMID- 22148533
TI  - Water resources: a global problem with local roots.

PMID- 22148535
TI  - Steady-state measurement of krypton-85-air diffusion coefficients in porous
      media.

PMID- 22148534
TI  - The movement of some herbicides in soils.  Linear diffusion and convection of
      chemicals in soils.

PMID- 22148536
TI  - Effects of temperature and of ultraviolet radiation on pyrene absorbed on garden
      soil.

PMID- 22148537
TI  - Gamma irradiation of dilute aqueous alkyl benzenesulfonate solutions.

PMID- 22148538
TI  - Relative importance of viscosity and oxygen solubility on oxygen transfer rates
      in glucose solutions.

PMID- 22148539
TI  - New products digest.

PMID- 22148540
TI  - New literature.

PMID- 22148541
TI  - California's Calamity or How to Mismanage Water.

PMID- 22148543
TI  - Preparation of a poly-nanocage dynamer: correlating the growth of polymer strands
      using constitutional dynamic chemistry and heteroleptic aggregation.
AB  - A metallosupramolecular prismatic nanocage with altogether six reactive aldehyde
      terminals was utilized as a sophisticated "monomer" in a template-directed
      constitutional dynamic imine polymerization to prepare an unprecedented triple
      stranded dynamer. To analyze the correlated growth in its three congener strands,
      a fully covalent triple-armed star polymer was fabricated from the metallodynamer
      through capping, imine reduction, and removal of the template. Atomic force
      microscopy analysis of 68 triple-armed star polymer molecules suggests that the
      growth of their arms is correlated to ~72%.

PMID- 22148544
TI  - Substituted diazatetracyclo[4.4.0.1(3,10).1(5,8)]dodecanes as stable caged proton
      sponges.
AB  - Herein, we report a molecular framework design differing significantly from the
      traditional topology of proton sponges. We developed a synthetic approach to the
      preparation of caged secondary amines by acid-catalyzed rearrangement of fused
      tetracyclic heterocycles synthesized by intramolecular criss-cross cycloaddition.
      Alkylation of amines led to air nonsensitive
      diazatetracyclo[4.4.0.1(3,10).1(5,8)]dodecanes (DTDs) with rare alicyclic
      scaffolding in high overall yields. Their pK(BH)+ values were determined by
      transprotonation experiments as well as their sensitivity toward nucleophiles,
      acids and bases. Crystal structures of free base and monoprotonated form are
      discussed.

PMID- 22148545
TI  - Decay of Bacteroidales genetic markers in relation to traditional fecal
      indicators for water quality modeling of drinking water sources.
AB  - The implementation of microbial fecal source tracking (MST) methods in drinking
      water management is limited by the lack of knowledge on the transport and decay
      of host-specific genetic markers in water sources. To address these limitations,
      the decay and transport of human (BacH) and ruminant (BacR) fecal Bacteroidales
      16S rRNA genetic markers in a drinking water source (Lake Radasjon in Sweden)
      were simulated using a microbiological model coupled to a three-dimensional
      hydrodynamic model. The microbiological model was calibrated using data from
      outdoor microcosm trials performed in March, August, and November 2010 to
      determine the decay of BacH and BacR markers in relation to traditional fecal
      indicators. The microcosm trials indicated that the persistence of BacH and BacR
      in the microcosms was not significantly different from the persistence of
      traditional fecal indicators. The modeling of BacH and BacR transport within the
      lake illustrated that the highest levels of genetic markers at the raw water
      intakes were associated with human fecal sources (on-site sewers and emergency
      sewer overflow). This novel modeling approach improves the interpretation of MST
      data, especially when fecal pollution from the same host group is released into
      the water source from different sites in the catchment.

PMID- 22148546
TI  - Enantiomer-specific bioactivities of peptidomimetic analogues of mastoparan and
      mitoparan: characterization of inverso mastoparan as a highly efficient cell
      penetrating peptide.
AB  - Retro-inverso transformation has commonly been employed as a strategy both for
      the synthesis of proteolytically stable peptide analogues and for the detailed
      investigation of structure activity relationships. Herein, we adopted a similar
      strategy to probe the structure activity relationships of two biologically active
      tetradecapeptides. Analogues of the alpha-helical mastoparan, and the highly
      potent apoptogenic analogue mitoparan, were synthesized using d-amino acids
      assembled in both endogenous (inverso) and reverse (retro-inverso) orientations.
      For a more comprehensive comparison, our studies also included the retro l
      enantiomer of both peptides. Contrary to expectation, comparative investigations
      of cytotoxicity, mast cell degranulation, and cellular penetration demonstrated
      that, while retro-inverso transformation abrogated the associated biological
      activities of these helical peptides, inverso homologues retained their
      bioactivities. Moreover, inverso mastoparan demonstrated the highest
      translocation efficacy of all analogues with much improved uptake kinetics
      compared to other cell penetrating peptides (CPPs) including the commonly
      employed inert vectors penetratin and tat. Data presented herein thus propound
      the utility of inverso mastoparan as a highly efficient peptide vector.
      Furthermore, correlation analysis of plasma membrane translocation and
      intracellular uptake efficacy further supports a two-compartment model of CPP
      import whereby the intracellular accumulation of polycationic peptides is
      dependent upon both the efficiency of transport into the cell and their
      subsequent accretion at distinct subcellular loci.

PMID- 22148547
TI  - Measuring binding and speciation of hydrophobic organic chemicals at controlled
      freely dissolved concentrations and without phase separation.
AB  - The binding and speciation of hydrophobic organic chemicals (HOCs) in aqueous
      solutions were determined by controlling chemical activity and measuring total
      concentrations. Passive dosing was applied to control chemical activities of HOCs
      in aqueous solutions by equilibrium partitioning from a poly(dimethylsiloxane)
      polymer preloaded with the chemicals. The HOC concentrations in the equilibrated
      solutions [C(solution(eq))] and water [C(water(eq))] were then measured. Free
      fractions of the HOCs were determined as C(water(eq))/C(solution(eq)), whereas
      enhanced capacities (E) of the solutions for HOCs were determined as
      C(solution(eq))/C(water(eq)). A mixture of polycyclic aromatic hydrocarbons
      served as model analytes, while humic acid, sodium dodecyl sulfate, hydroxypropyl
      beta-cyclodextrin, and NaCl served as model medium constituents. The enhanced
      capacities were plotted versus the concentrations of medium constituents, and
      simple linear regression provided precise partition ratios, salting out
      constants, and critical micelle concentrations. These parameters were generally
      in good agreement with published values obtained by solid phase microextraction
      and fluorescence quenching. The very good precision was indicated by the low
      relative standard errors for the partition ratios of 0.5-8%, equivalent to 0.002
      0.03 log unit. This passive dosing approach allows binding and speciation of HOCs
      to be studied without any phase separation steps or mass balance assumptions.

PMID- 22148548
TI  - Design, synthesis, and applications of potential substitutes of t-Bu
      phosphinooxazoline in Pd-catalyzed asymmetric transformations and their use for
      the improvement of the enantioselectivity in the Pd-catalyzed allylation reaction
      of fluorinated allyl enol carbonates.
AB  - The design, synthesis, and applications of potential substitutes of t-Bu-PHOX in
      asymmetric catalysis is reported. The design relies on the incorporation of
      geminal substituents at C5 in combination with a substituent at C4 other than t
      butyl (i-Pr, i-Bu, or s-Bu). Most of these new members of the PHOX ligand family
      behave similarly in terms of stereoinduction to t-Bu-PHOX in three palladium
      catalyzed asymmetric transformations. Electronically modified ligands were also
      prepared and used to improve the enantioselectivity in the Pd-catalyzed
      allylation reaction of fluorinated allyl enol carbonates.

PMID- 22148550
TI  - Reversible alteration of CO2 adsorption upon photochemical or thermal treatment
      in a metal-organic framework.
AB  - A metal-organic framework (MOF) for reversible alteration of guest molecule
      adsorption, here carbon dioxide, upon photochemical or thermal treatment has been
      discovered. An azobenzene functional group, which can switch its conformation
      upon light irradiation or heat treatment, has been introduced to the organic
      linker of a MOF. The resulting MOF adsorbs different amount of CO(2) after UV or
      heat treatment. This remarkable stimuli-responsive adsorption effect has been
      demonstrated through experiments.

PMID- 22148549
TI  - Design and evaluation of multifunctional nanocarriers for selective delivery of
      coenzyme Q10 to mitochondria.
AB  - Impairments of mitochondrial functions have been associated with failure of
      cellular functions in different tissues, leading to various pathologies. We
      report here a mitochondria-targeted nanodelivery system for coenzyme Q10 (CoQ10)
      that can reach mitochondria and deliver CoQ10 in adequate quantities.
      Multifunctional nanocarriers based on ABC miktoarm polymers (A = poly(ethylene
      glycol (PEG), B = polycaprolactone (PCL), and C = triphenylphosphonium bromide
      (TPPBr)) were synthesized using a combination of click chemistry with ring
      opening polymerization, self-assembled into nanosized micelles, and were employed
      for CoQ10 loading. Drug loading capacity (60 wt %), micelle size (25-60 nm), and
      stability were determined using a variety of techniques. The micelles had a small
      critical association concentration and were colloidally stable in solution for
      more than 3 months. The extraordinarily high CoQ10 loading capacity in the
      micelles is attributed to good compatibility between CoQ10 and PCL, as indicated
      by the low Flory-Huggins interaction parameter. Confocal microscopy studies of
      the fluorescently labeled polymer analog together with the mitochondria-specific
      vital dye label indicated that the carrier did indeed reach mitochondria. The
      high CoQ10 loading efficiency allowed testing of micelles within a broad
      concentration range and provided evidence for CoQ10 effectiveness in two
      different experimental paradigms: oxidative stress and inflammation. Combined
      results from chemical, analytical, and biological experiments suggest that the
      new miktoarm-based carrier provides a suitable means of CoQ10 delivery to
      mitochondria without loss of drug effectiveness. The versatility of the click
      chemistry used to prepare this new mitochondria-targeting nanocarrier offers a
      widely applicable, simple, and easily reproducible procedure to deliver drugs to
      mitochondria or other intracellular organelles.

PMID- 22148551
TI  - Combining global and local measures for structure-based druggability predictions.
AB  - Predicting druggability and prioritizing certain disease modifying targets for
      the drug development process is of high practical relevance in pharmaceutical
      research. DoGSiteScorer is a fully automatic algorithm for pocket and
      druggability prediction. Besides consideration of global properties of the
      pocket, also local similarities shared between pockets are reflected.
      Druggability scores are predicted by means of a support vector machine (SVM),
      trained, and tested on the druggability data set (DD) and its nonredundant
      version (NRDD). The DD consists of 1069 targets with assigned druggable,
      difficult, and undruggable classes. In 90% of the NRDD, the SVM model based on
      global descriptors correctly classifies a target as either druggable or
      undruggable. Nevertheless, global properties suffer from binding site changes due
      to ligand binding and from the pocket boundary definition. Therefore, local
      pocket properties are additionally investigated in terms of a nearest neighbor
      search. Local similarities are described by distance dependent histograms between
      atom pairs. In 88% of the DD pocket set, the nearest neighbor and the structure
      itself conform with their druggability type. A discriminant feature between
      druggable and undruggable pockets is having less short-range hydrophilic
      hydrophilic pairs and more short-range lipophilic-lipophilic pairs. Our findings
      for global pocket descriptors coincide with previously published methods
      affirming that size, shape, and hydrophobicity are important global pocket
      descriptors for automatic druggability prediction. Nevertheless, the variety of
      pocket shapes and their flexibility upon ligand binding limit the automatic
      projection of druggable features onto descriptors. Incorporating local pocket
      properties is another step toward a reliable descriptor-based druggability
      prediction.

PMID- 22148552
TI  - ZnO hollow quantum dot: a promising deep-UV light emitter.
AB  - We establish an analytic model to illustrate the energy bandgap of ZnO hollow
      quantum dots (HQDs) with negative curvature surface from the perspective of
      nanothermodynamics. It was found that the bandgap of ZnO HQDs shows a pronounced
      blue-shift as comparable to those of bulk counterpart and free nanocrystals.
      Furthermore, the photoelectric properties of ZnO HQDs can be effectively
      modulated by three independent dimensions, including the outer surface, the inner
      surface and the shell thickness. Strikingly, the emission wavelength of ZnO HQDs
      can be extended into the deep-ultraviolet (DUV) region, which suggests this kind
      of nanostructure could be expected to be applicable for the new-generation,
      compact, and environmentally friendly alternative DUV light emitter.

PMID- 22148553
TI  - Flavin-linked Erv-family sulfhydryl oxidases release superoxide anion during
      catalytic turnover.
AB  - Typically, simple flavoprotein oxidases couple the oxidation of their substrates
      with the formation of hydrogen peroxide without release of significant levels of
      the superoxide ion. However, two evolutionarily related single-domain sulfhydryl
      oxidases (Erv2p; a yeast endoplasmic reticulum resident protein and augmenter of
      liver regeneration, ALR, an enzyme predominantly found in the mitochondrial
      intermembrane) release up to ~30% of the oxygen they reduce as the superoxide
      ion. Both enzymes oxidize dithiol substrates via a redox-active disulfide
      adjacent to the flavin cofactor within the helix-rich Erv domain. Subsequent
      reduction of the flavin is followed by transfer of reducing equivalents to
      molecular oxygen. Superoxide release was initially detected using tris(3
      hydroxypropyl)phosphine (THP) as an alternative reducing substrate to
      dithiothreitol (DTT). THP, and other phosphines, showed anomalously high turnover
      numbers with Erv2p and ALR in the oxygen electrode, but oxygen consumption was
      drastically suppressed upon the addition of superoxide dismutase. The superoxide
      ion initiates a radical chain reaction promoting the aerobic oxidation of
      phosphines with the formation of hydrogen peroxide. Use of a known flux of
      superoxide generated by the xanthine/xanthine oxidase system showed that one
      superoxide ion stimulates the reduction of 27 and 4.5 molecules of oxygen using
      THP and tris(2-carboxyethyl)phosphine (TCEP), respectively. This superoxide
      dependent amplification of oxygen consumption by phosphines provides a new
      kinetic method for the detection of superoxide. Superoxide release was also
      observed by a standard chemiluminescence method using a luciferin analogue (MCLA)
      when 2 mM DTT was employed as a substrate of Erv2p and ALR. The percentage of
      superoxide released from Erv2p increased to ~65% when monomeric mutants of the
      normally homodimeric enzyme were used. In contrast, monomeric multidomain
      quiescin sulfhydryl oxidase enzymes that also contain an Erv FAD-binding fold
      release only 1-5% of their total reduced oxygen species as the superoxide ion.
      Aspects of the mechanism and possible physiological significance of superoxide
      release from these Erv-domain flavoproteins are discussed.

PMID- 22148554
TI  - Biotransformation of the neonicotinoid insecticide thiacloprid by the bacterium
      Variovorax boronicumulans strain J1 and mediation of the major metabolic pathway
      by nitrile hydratase.
AB  - A neonicotinoid insecticide thiacloprid-degrading bacterium strain J1 was
      isolated from soil and identified as  Variovorax boronicumulans  by 16S rRNA gene
      sequence analysis. Liquid chromatography-mass spectrometry and nuclear magnetic
      resonance analysis indicated the major pathway of thiacloprid (THI) metabolism by
      V. boronicumulans J1 involved hydrolysis of the N-cyanoimino group to form an N
      carbamoylinino group containing metabolite, THI amide. Resting cells of V.
      boronicumulans J1 degraded 62.5% of the thiacloprid at a concentration of 200
      mg/L in 60 h, and 98% of the reduced thiacloprid was converted to the final
      metabolite thiacloprid amide. A 2.6 kb gene cluster from V. boronicumulans J1
      that includes the full length of the nitrile hydratase gene was cloned and
      investigated by degenerate primer polymerase chain reaction (PCR) and inverse
      PCR. The nitrile hydratase gene has a length of 1304 bp and codes a cobalt-type
      nitrile hydratase with an alpha-subunit of 213 amino acids and a beta-subunit of
      221 amino acids. The nitrile hydratase gene was recombined into plasmid pET28a
      and overexpressed in  Escherichia coli  BL21 (DE3). The resting cells of
      recombinant E. coli BL21 (DE3)-pET28a-NHase with overexpression of nitrile
      hydratase transformed thiacloprid to its amide metabolite, whereas resting cells
      of the control E. coli BL21 (DE3)-pET28a did not. Therefore, the major hydration
      pathway of thiacloprid is mediated by nitrile hydratase.

PMID- 22148555
TI  - Fluorocyclines. 2. Optimization of the C-9 side-chain for antibacterial activity
      and oral efficacy.
AB  - Utilizing a fully synthetic route to tetracycline analogues, the C-9 side-chain
      of the fluorocyclines was optimized for both antibacterial activity and oral
      efficacy. Compounds were identified that overcome both efflux (tet(K), tet(A))
      and ribosomal protection (tet(M)) tetracycline-resistance mechanisms and are
      active against Gram-positive and Gram-negative organisms. A murine systemic
      infection model was used as an oral efficacy screen to rapidly identify compounds
      with oral bioavailability. Two compounds were identified that exhibit both oral
      bioavailability in rat and clinically relevant bacterial susceptibility profiles
      against major respiratory pathogens. One compound demonstrated oral efficacy in
      rodent lung infection models that was comparable to marketed antibacterial
      agents.

PMID- 22148558
TI  - Editorial - The world wears a mixed mantle of beauty and grime.

PMID- 22148556
TI  - X-ray structures of Sc2C2@C2n (n = 40-42): in-depth understanding of the core
      shell interplay in carbide cluster metallofullerenes.
AB  - X-ray analyses of the cocrystals of a series of carbide cluster metallofullerenes
      Sc(2)C(2)@C(2n) (n = 40-42) with cobalt(II) octaethylporphyrin present new
      insights into the molecular structures and cluster-cage interactions of these
      less-explored species. Along with the unambiguous identification of the cage
      structures for the three isomers of Sc(2)C(2)@C(2v)(5)-C(80), Sc(2)C(2)@C(3v)(8)
      C(82), and Sc(2)C(2)@D(2d)(23)-C(84), a clear correlation between the cluster
      strain and cage size is observed in this series: Sc-Sc distances and dihedral
      angles of the bent cluster increase along with cage expansion, indicating that
      the bending strain within the cluster makes it pursue a planar structure to the
      greatest degree possible. However, the C-C distances within Sc(2)C(2) remain
      unchanged when the cage expands, perhaps because of the unusual bent structure of
      the cluster, preventing contact between the cage and the C(2) unit. Moreover,
      analyses revealed that larger cages provide more space for the cluster to rotate.
      The preferential formation of cluster endohedral metallofullerenes for scandium
      might be associated with its small ionic radius and the strong coordination
      ability as well.

PMID- 22148560
TI  - Ingenuity and incinerators.

PMID- 22148559
TI  - Environmental currents.

PMID- 22148561
TI  - Modular Desalting Plants have Wide Utility.

PMID- 22148562
TI  - Effective water pollution control requires accurate data.

PMID- 22148563
TI  - Quote...People might enjoy city life.

PMID- 22148564
TI  - Thermal pollution of water systems.

PMID- 22148565
TI  - Fractionation of organic matter in natural waters on Sephadex columns.

PMID- 22148566
TI  - Gas-liquid chromatographic separation of some organophosphate pesticides, their
      hydrolysis products, and oxons.

PMID- 22148568
TI  - Comparison of natural and urban aerosol distribution measured with the aerosol
      spectrometer.

PMID- 22148567
TI  - Effects of air pollutants on apparent photosynthesis and water use by citrus
      trees.

PMID- 22148569
TI  - Singlet oxygen in the environmental sciences.  Role of singlet molecular oxygen
      in the production of photochemical air pollution.

PMID- 22148570
TI  - Gas analysis by polymer chain scission.  Ozonolysis of polystyrene.

PMID- 22148571
TI  - Nucleation of crystalline phases from sea water and sea water concentrates.

PMID- 22148572
TI  - New products digest.

PMID- 22148573
TI  - New literature digest.

PMID- 22148574
TI  - Balancing environmental quality against cost.

PMID- 22148575
TI  - Effects of DNA methylation on the structure of nucleosomes.
AB  - Nucleosomes are the fundamental packing units of the eukaryotic genome.
      Understanding the dynamic structure of a nucleosome is a key to the elucidation
      of genome packaging in eukaryotes, which is tied to the mechanisms of gene
      regulation. CpG methylation of DNA is an epigenetic modification associated with
      the inactivation of transcription and the formation of a repressive chromatin
      structure. Unraveling the changes in the structure of nucleosomes upon CpG
      methylation is an essential step toward the understanding of the mechanisms of
      gene repression and silencing by CpG methylation. Here we report single-molecule
      and ensemble fluorescence studies showing how the structure of a nucleosome is
      affected by CpG methylation. The results indicate that CpG methylation induces
      tighter wrapping of DNA around the histone core accompanied by a topology change.
      These findings suggest that changes in the physical properties of nucleosomes
      induced upon CpG methylation may contribute directly to the formation of a
      repressive chromatin structure.

PMID- 22148578
TI  - Magnetic silica nanoparticle cellular uptake and cytotoxicity regulated by
      electrostatic polyelectrolytes-DNA loading at their surface.
AB  - Magnetic silica nanoparticles show great promise for drug delivery. The major
      advantages correspond to their magnetic nature and ease of biofunctionalization,
      which favors their ability to interact with cells and tissues. We have prepared
      magnetic silica nanoparticles with DNA fragments attached on their previously
      polyelectrolyte-primed surface. The remarkable feature of these materials is the
      compromise between the positive charges of the polyelectrolytes and the negative
      charges of the DNA. This dual-agent formulation dramatically changes the overall
      cytotoxicity and chemical degradation of the nanoparticles, revealing the key
      role that surface functionalization plays in regulating the mechanisms involved.

PMID- 22148577
TI  - Chasing phosphohistidine, an elusive sibling in the phosphoamino acid family.
AB  - This year (2012) marks the 50th anniversary of the discovery of protein histidine
      phosphorylation. Phosphorylation of histidine (pHis) is now widely recognized as
      being critical to signaling processes in prokaryotes and lower eukaryotes.
      However, the modification is also becoming more widely reported in mammalian
      cellular processes and implicated in certain human disease states such as cancer
      and inflammation. Nonetheless, much remains to be understood about the role and
      extent of the modification in mammalian cell biology. Studying the functional
      role of pHis in signaling, either in vitro or in vivo, has proven devilishly
      hard, largely due to the chemical instability of the modification. As a
      consequence, we are currently handicapped by a chronic lack of chemical and
      biochemical tools with which to study histidine phosphorylation. Here, we discuss
      the challenges associated with studying the chemical biology of pHis and review
      recent progress that offers some hope that long-awaited biochemical reagents for
      studying this elusive posttranslational modification (PTM) might soon be
      available.

PMID- 22148579
TI  - Executing and rationalizing the synthesis of a difluorinated analogue of a ring
      expanded calystegine B2.
AB  - A difluorinated analogue of a ring-expanded calystegine B(2) and some N-protected
      species were prepared via microwave-mediated transannular ring-opening of an
      epoxyketone. The diastereofacial selectivity of the epoxidation reaction, which
      delivers the key intermediate, and the regioselectivity of the transannular
      reactions were analyzed by density functional theory (DFT) methods. The
      epoxidation stereoselectivity arises from simple steric control, whereas the ring
      closure reactions are subject to thermodynamic control.

PMID- 22148580
TI  - Toluene depletion in produced oil contributes to souring control in a field
      subjected to nitrate injection.
AB  - Souring in the Medicine Hat Glauconitic C field, which has a low bottom-hole
      temperature (30  degrees C), results from the presence of 0.8 mM sulfate in the
      injection water. Inclusion of 2 mM nitrate to decrease souring results in zones
      of nitrate-reduction, sulfate-reduction, and methanogenesis along the injection
      water flow path. Microbial community analysis by pyrosequencing indicated
      dominant community members in each of these zones. Nitrate breakthrough was
      observed in 2-PW, a major water- and sulfide-producing well, after 4 years of
      injection. Sulfide concentrations at four other production wells (PWs) also
      reached zero, causing the average sulfide concentration in 14 PWs to decrease
      significantly. Interestingly, oil produced by 2-PW was depleted of toluene, the
      preferred electron donor for nitrate reduction. 2-PW and other PWs with zero
      sulfide produced 95% water and 5% oil. At 2 mM nitrate and 5 mM toluene,
      respectively, this represents an excess of electron acceptor over electron donor.
      Hence, continuous nitrate injection can change the composition of produced oil
      and nitrate breakthrough is expected first in PWs with a low oil to water ratio,
      because oil from these wells is treated on average with more nitrate than is oil
      from PWs with a high oil to water ratio.

PMID- 22148581
TI  - Highly sensitive photoelectrochemical immunoassay with enhanced amplification
      using horseradish peroxidase induced biocatalytic precipitation on a CdS quantum
      dots multilayer electrode.
AB  - Herein we demonstrate the protocol of a biocatalytic precipitation (BCP)-based
      sandwich photoelectrochemical (PEC) horseradish peroxidase (HRP)-linked
      immunoassay on the basis of their synergy effect for the ultrasensitive detection
      of mouse IgG (antigen, Ag) as a model protein. The hybrid film consisting of
      oppositely charged polyelectrolytes and CdS quantum dots (QDs) is developed by
      the classic layer by layer (LbL) method and then employed as the photoactive
      antibody (Ab) immobilization matrix for the subsequent sandwich-type Ab-Ag
      affinity interactions. Improved sensitivity is achieved through using the
      bioconjugates of HRP-secondary antibodies (Ab(2)). In addition to the much
      enhanced steric hindrance compared with the original one, the presence of HRP
      would further stimulate the BCP onto the electrode surface for signal
      amplification, concomitant to a competitive nonproductive absorption that lowers
      the photocurrent intensity. As a result of the multisignal amplification in this
      HRP catalyzed BCP-based PEC immunoassay, it possesses excellent analytical
      performance. The antigen could be detected from 0.5 pg/mL to 5.0 ng/mL with a
      detection limit of 0.5 pg/mL.

PMID- 22148583
TI  - DFT energy optimization of a large carbohydrate: cyclomaltohexaicosaose (CA-26).
AB  - CA-26 is the largest cyclodextrin (546 atoms) for which refined X-ray structural
      data is available. Because of its size, 26 D-glucose residues, it is beyond the
      scope of study of most ab initio or density functional methods and to date has
      only been computationally examined using empirical force fields. The crystal
      structure of CA-26 is folded like a figure "8" into two 10 D-glucoses long
      antiparallel left-handed V (Verkleisterung)-type helices with a "band-flip" and
      "kink" at the top and bottom of the helices. DFTr methods were applied to CA-26
      to determine if a carbohydrate molecule of this size could be geometry optimized
      and if it would show structural variances from application of dispersion and/or
      solvation. The DFTr reduced basis set method developed by the authors uses 4-31G
      on the carbon atoms of the glucose rings and 6-31+G* on all other atoms. B3LYP is
      the density functional used to successfully optimize CA-26, and other density
      functionals were then applied, including a self-consistent charge density
      functional tight binding (SCC-DFTB) method and the B97D (dispersion-corrected)
      and B97D-PCM (dispersion + implicit solvent) methods. Heavy atom coordinates were
      taken from one X-ray structure, fitted with hydrogen atoms, and geometry
      optimized using PM3 followed by B3LYP/6-31+G*/4-31G optimization. After
      optimization, the heavy atom rms deviation of the optimized DFTr (B3LYP)
      structure to the crystal structure was 0.89 A, the rmsd of the B97D optimization
      was 1.38 A, that for B97D-PCM was 0.95 A, and that for SCC-DFTB was 0.94 A. These
      results are very good considering that no explicit water molecules were included
      in the computational analysis and there were ~32-38 water molecules around each
      CA-26 molecule in the crystal structure. Tables of internal coordinates and
      puckering parameters were compared to the X-ray structures, and close
      correspondence was found.

PMID- 22148582
TI  - Synthesis and evaluation of novel Tc-99m labeled probestin conjugates for imaging
      APN/CD13 expression in vivo.
AB  - The enzyme aminopeptidase N (APN, also known as CD13) is known to play an
      important role in tumor proliferation, attachment, angiogenesis, and tumor
      invasion. In this study, we hypothesized that a radiolabeled high affinity APN
      inhibitor could be potentially useful for imaging APN expression in vivo. Here,
      we report synthesis, radiolabeling, and biological evaluation of new probestin
      conjugates containing a tripeptide, N,N-dimethylglycyl-l-lysinyl-l-cysteinylamide
      (N(3)S), chelator. New probestin conjugates were synthesized by solid-phase
      peptide synthesis method, purified by reversed-phase HPLC, and characterized by
      electrospray mass spectrometry. The conjugates were complexed with Re(V) and
      (99m)Tc(V) by transmetalation using corresponding Re(V) or (99m)Tc(V) gluconate
      synthon. The mass spectral analyses of ReO-N(3)S-Probestin conjugates were
      consistent with the formation of neutral Re(V)O-N(3)S complexes. Initial
      biological activity of ReO-N(3)S-Probestin conjugates determined by performing an
      in vitro APN enzyme assay using intact HT-1080 cells demonstrated higher
      inhibition of APN enzyme activity than bestatin. In vivo biodistribution and
      whole body planar imaging studies of (99m)TcO-N(3)S-PEG(2)-Probestin performed in
      nude mice xenografted with human fibrosarcoma tumors derived from HT-1080 cells
      demonstrated a tumor uptake value of 2.88 +/- 0.64%ID/g with tumor-to-blood and
      tumor-to-muscle ratios of 4.8 and 5.3, respectively, at 1 h postinjection (p.i.).
      Tumors were clearly visible in whole body planar image obtained at 1 h p.i., but
      not when the APN was competitively blocked with a coinjection of excess
      nonradioactive ReO-N(3)S-PEG(2)-Probestin conjugate. These results demonstrate
      the feasibility of using high affinity APN inhibitor conjugates as targeting
      vectors for in vivo targeting of APN.

PMID- 22148584
TI  - Small molecule STAT5-SH2 domain inhibitors exhibit potent antileukemia activity.
AB  - A growing body of evidence shows that Signal Transducer and Activator of
      Transcription 5 (STAT5) protein, a key member of the STAT family of signaling
      proteins, plays a pivotal role in the progression of many human cancers,
      including acute myeloid leukemia and prostate cancer. Unlike STAT3, where
      significant medicinal effort has been expended to identify potent direct
      inhibitors, Stat5 has been poorly investigated as a molecular therapeutic target.
      Thus, in an effort to identify direct inhibitors of STAT5 protein, we conducted
      an in vitro screen of a focused library of SH2 domain binding salicylic acid
      containing inhibitors (~150) against STAT5, as well as against STAT3 and STAT1
      proteins for SH2 domain selectivity. We herein report the identification of
      several potent (K(i) < 5 MUM) and STAT5 selective (>3-fold specificity for STAT5
      cf. STAT1 and STAT3) inhibitors, BP-1-107, BP-1-108, SF-1-087, and SF-1-088. Lead
      agents, evaluated in K562 and MV-4-11 human leukemia cells, showed potent
      induction of apoptosis (IC(50)'s ~ 20 MUM) which correlated with potent and
      selective suppression of STAT5 phosphorylation, as well as inhibition of STAT5
      target genes cyclin D1, cyclin D2, C-MYC, and MCL-1. Moreover, lead agent BP-1
      108 showed negligible cytotoxic effects in normal bone marrow cells not
      expressing activated STAT5 protein. Inhibitors identified in this study represent
      some of the most potent direct small molecule, nonphosphorylated inhibitors of
      STAT5 to date.

PMID- 22148585
TI  - Simultaneous determination of five plant growth regulators in fruits by modified
      quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction and liquid
      chromatography-tandem mass spectrometry.
AB  - An effective method using liquid chromatography-tandem mass spectrometry (LC
      MS/MS) was developed and optimized to obtain a complete separation of five
      representative plant growth regulators (PGRs) [gibberellic acid, 2,4
      dichlorophenoxyacetic acid (2,4-D), thidiazuron, forchlorfenuron, and
      paclobutrazol] in fruits. Extraction was performed with acetonitrile containing
      0.1% (v/v) acetic acid, applying modified quick, easy, cheap, effective, rugged,
      and safe (QuEChERS) methodology. LC-MS/MS conditions including composition of
      mobile phases and mass spectrometry (MS) conditions were evaluated to achieve the
      highest sensitivity in MS detection. All of the data acquisition was employed in
      the segmented multiple-reaction monitoring mode for the selected negative and
      positive transition ions. The octadecylsilyl (C18) dispersive solid-phase
      extraction (SPE) sorbent was found to provide the more satisfied recoveries than
      primary secondary amine (PSA) and graphitized carbon black (GCB) for five target
      PGRs. The optimized method allowed for recoveries of 76-112% for the five PGRs
      from fruit samples with relative standard deviation (RSD) values less than 10%.
      Limits of quantification (0.5-16.5 MUg/kg) were lower than the maximum limit of
      residues established for PGRs. The results demonstrated that the developed LC
      MS/MS and QuEChERS extraction method is highly effective for analyzing trace
      amounts of target PGRs in fruit samples. Finally, the method was successfully
      used to detect residual PGRs in Beijing, China, in 2010. The concentrations of
      2,4-D (5.1-1503 MUg/kg) and paclobutrazol (1-1381 MUg/kg) found in orange and
      peach, respectively, suggesting that the use of these PGRs in these fruits should
      be regulated in China in the future.

PMID- 22148586
TI  - Easy route to the wettability cycling of copper surface between
      superhydrophobicity and superhydrophilicity.
AB  - A hierarchical copper structure combining micro- and nanogaps/pores was built up
      on copper substrate by etching and electrodeposition. The fresh as-deposited
      copper was easily oxidized in air at room temperature, forming a CuO layer
      covering on the surface. The surface could be hydrophobized with thiol-modified
      fluorocarbons, after which it showed a water contact angle as high as 165 degrees
      +/- 2 degrees . This surface could also regain the superhydrophilicity with a
      zero water contact angel after annealing at 200  degrees C for 10 min to desorb
      the low surface energy monolayer of thiol-modified fluorocarbons and reform a CuO
      layer again on the surface. Repeating the process of adsorption/desorption of the
      monolayer by modification and annealing, it was successful to fulfill the
      wettability cycling between superhydrophobicity and superhydrophilicity on the
      copper surface. The adsorption and desorption mechanism of the monolayer was
      discussed based on the result of surface chemistry analysis.

PMID- 22148587
TI  - Hammett correlations in the chemistry of 3-phenylpropyl radicals.
AB  - The energetics and kinetics of the reaction of variously substituted benzyl
      radicals with a model alkene were calculated at the G3(MP2)-RAD//B3-LYP/6-31G(d)
      level of theory to determine whether such reactions are amenable to Hammett
      analysis. The reactions were studied both in the gas phase and in toluene
      solution in the temperature range 298-353 K; calculations include 1D-hindered
      rotor corrections for low frequency torsional modes, and the solvation energies
      were calculated using COSMO-RS at the BP/TZP level of theory. The addition
      reaction was found to be dominated by radical stabilization effects, but under
      circumstances where olefin substituent effects were decoupled from aryl
      substituent effects, a modest polar effect comes into play, which is enhanced by
      solvation. Reasonable correlations with empirical substituent parameters such as
      Hammett sigma and sigma(*) are observed for the enthalpy of activation, but
      additional entropic factors act to decrease the degree of correlation with
      respect to free energies and rate coefficients, confirming hypotheses from
      earlier experimental work. Substituent effects on the reverse beta-fragmentation
      reaction, and potential cyclization of the 3-phenylpropyl radicals formed by
      addition are also discussed.

PMID- 22148588
TI  - Cooperative template-directed assembly of mesoporous metal-organic frameworks.
AB  - Despite great efforts, the development of a reliable way to assemble mesoporous
      metal-organic frameworks (mesoMOFs) remains a challenge. In this work, we have
      designed a cooperative template system, comprising a surfactant
      (cetyltrimethylammonium bromide) and a chelating agent (citric acid), for the
      generation of a mesoMOF containing a hierarchical system of mesopores
      interconnected with microspores. The surfactant molecules form micelles and the
      chelating agent bridges the MOF and the micelles, making self-assembly and
      crystal growth proceed under the direction of the cooperative template. However,
      when the surfactant or the chelating agent was applied individually, no mesoMOF
      was obtained.

PMID- 22148589
TI  - A structure-based approach to understanding somatostatin receptor-4 agonism
      (sst4).
AB  - It has been reported that somatostatin receptor subtypes 4 and 5 would be high
      impact templates for homology modeling if their 3D structures became available.
      We have generated a homology model of the somatostatin receptor subtype 4 (sst4),
      using the newest active state beta(2) adrenoreceptor crystal structure, and
      subsequently docked a variety of agonists into the model-built receptor to
      elucidate the binding modes of reported agonists. Using experimental restraints,
      we were able to explain observed activity profiles. We propose two binding modes
      that can consistently explain findings for high-affinity agonists and reason why
      certain structures display low affinities for the receptor.

PMID- 22148591
TI  - Chitin whiskers: an overview.
AB  - Chitin is the second most abundant semicrystalline polysaccharide. Like
      cellulose, the amorphous domains of chitin can also be removed under certain
      conditions such as acidolysis to give rise to crystallites in nanoscale, which
      are the so-called chitin nanocrystals or chitin whiskers (CHWs). CHW together
      with other organic nanoparticles such as cellulose whisker (CW) and starch
      nanocrystal show many advantages over traditional inorganic nanoparticles such as
      easy availability, nontoxicity, biodegradability, low density, and easy
      modification. They have been widely used as substitutes for inorganic
      nanoparticles in reinforcing polymer nanocomposites. The research and development
      of CHW related areas are much slower than those of CW. However, CHWs are still of
      strategic importance in the resource scarcity periods because of their abundant
      availability and special properties. During the past decade, increasing studies
      have been done on preparation of CHWs and their application in reinforcing
      polymer nanocomposites. Some other applications such as being used as feedstock
      to prepare chitosan nanoscaffolds have also been investigated. This Article is to
      review the recent development on CHW related studies.

PMID- 22148590
TI  - The Streptomyces-produced antibiotic fosfomycin is a promiscuous substrate for
      archaeal isopentenyl phosphate kinase.
AB  - Isopentenyl phosphate kinase (IPK) catalyzes the phosphorylation of isopentenyl
      phosphate to form the isoprenoid precursor isopentenyl diphosphate in the
      archaeal mevalonate pathway. This enzyme is highly homologous to fosfomycin
      kinase (FomA), an antibiotic resistance enzyme found in a few strains of
      Streptomyces and Pseudomonas whose mode of action is inactivation by
      phosphorylation. Superposition of Thermoplasma acidophilum (THA) IPK and FomA
      structures aligns their respective substrates and catalytic residues, including
      H50 and K14 in THA IPK and H58 and K18 in Streptomyces wedmorensis FomA. These
      residues are conserved only in the IPK and FomA members of the phosphate
      subdivision of the amino acid kinase family. We measured the fosfomycin kinase
      activity of THA IPK [K(m) = 15.1 +/- 1.0 mM, and k(cat) = (4.0 +/- 0.1) * 10-2 s
      1], resulting in a catalytic efficiency (k(cat)/K(m) = 2.6 M-1 s-1) that is 5
      orders of magnitude lower than that of the native reaction. Fosfomycin is a
      competitive inhibitor of IPK (K(i) = 3.6 +/- 0.2 mM). Molecular dynamics
      simulation of the IPK.fosfomycin.MgATP complex identified two binding poses for
      fosfomycin in the IP binding site, one of which results in a complex analogous to
      the native IPK.IP.ATP complex that engages H50 and the lysine triangle formed by
      K5, K14, and K205. The other binding pose leads to a dead-end complex that
      engages K204 near the IP binding site to bind fosfomycin. Our findings suggest a
      mechanism for acquisition of FomA-based antibiotic resistance in fosfomycin
      producing organisms.

PMID- 22148592
TI  - Electrochemical strategy for sensing protein phosphorylation.
AB  - We herein report a novel electrochemical method in this paper to monitor protein
      phosphorylation and to assay protein kinase activity based on Zr(4+) mediated
      signal transition and rolling circle amplification (RCA). First, substrate
      peptide immobilized on a gold electrode can be phosphorylated by protein kinase
      A. Then, Zr(4+) links phosphorylated peptide and DNA primer probe by interacting
      with the phosphate groups. After the introduction of the padlock probe and phi29
      DNA polymerase, RCA is achieved on the surface of the electrode. As the RCA
      product, a very long DNA strand, may absorb a large number of electrochemical
      speices, [Ru(NH(3))(6)](3+), via the electrostatic interaction, localizing them
      onto the electrode surface, initiated by protein kinase A, a sensitive
      electrochemical method to assay the enzyme activity is proposed. The detection
      limit of the method is as low as 0.5 unit/mL, which might promise this method as
      a good candidate for monitoring phosphorylation in the future.

PMID- 22148593
TI  - MicroRNA conjugated gold nanoparticles and cell transfection.
AB  - While the importance of microRNAs (miRNAs) in cancer treatment or manipulation of
      genetic expression has been increasingly recognized for developing miRNA-based
      therapies, the controlled delivery of miRNAs into specific cells constitutes a
      challenging task. This report describes preliminary findings from an
      investigation of the conjugation of gold nanoparticles with miRNAs (miRNA-AuNPs)
      and their cell transfection. The immobilization of miRNAs on the AuNPs was
      detected, and the surface stability was substantiated by gel electrophoresis
      assessment of the highly charged characteristics of miRNA-AuNPs and their surface
      exchange inactivity with a highly charged surfactant. The miRNA-AuNPs were tested
      in cell transfection using multiple myeloma cells, demonstrating efficient
      knockdown in the functional luciferase assay. The findings have important
      implications for understanding the mechanistic details of cell transfection
      involving miRNA-conjugated nanoparticles as biosensing or targeting probes.

PMID- 22148597
TI  - Editorial:  A bureau of environmental statistics.

PMID- 22148595
TI  - Asymmetric synthesis of trans-2,3-disubstituted indoline derivatives.
AB  - A novel method for asymmetric synthesis of trans-2,3-disubstituted indolines has
      been developed. The strategy involves the (-)-sparteine-mediated electrophilic
      substitution of 2-benzyl N-pivaloylaniline with aromatic or alpha,beta
      unsaturated aldehydes and subsequent intramolecular nucleophilic substitution.
      The simple protocol for two-step process can produce highly enantioenriched
      indolines 3a-o up to 98:2 er.

PMID- 22148599
TI  - Currents.

PMID- 22148598
TI  - Guest Editorial:  Selecting environmental analytical laboratories.

PMID- 22148600
TI  - A comparison of laboratory performances.

PMID- 22148602
TI  - Receptor models.

PMID- 22148601
TI  - Removing organic contaminants from groundwater.

PMID- 22148603
TI  - ES Views: Neutralization of acidic waters.

PMID- 22148604
TI  - Science and the EPA: Voodoo toxicology.

PMID- 22148605
TI  - Regulatory Focus: Criticism of research planning at EPA.

PMID- 22148606
TI  - Cyanide recovery across hollow fiber gas membranes.

PMID- 22148607
TI  - Photochemical formation of hydrogen peroxide in natural waters exposed to
      sunlight.

PMID- 22148608
TI  - Biodegradation studies of aniline and nitrobenzene in aniline plant wastewater by
      gas chromatography.

PMID- 22148609
TI  - Vanadium release from stabilized oil ash waste in seawater.

PMID- 22148610
TI  - Fate of sulfur(IV) dechlorinating agents in natural waters:  effect of suspended
      sediments.

PMID- 22148611
TI  - Fourier transform infrared and Raman spectra of dimethyl methylphosphonate
      adsorbed on montmorillonite.

PMID- 22148612
TI  - Degradation and dehalogenation of polychlorobiphenyls and halogenated aromatic
      molecules by superoxide ion and by electrolytic reduction.

PMID- 22148613
TI  - Small molecular weight organic amino nitrogen compounds in treated municipal
      wastewater.

PMID- 22148614
TI  - Identification of methoxylated phenols as candidate tracers for atmospheric wood
      smoke pollution.

PMID- 22148615
TI  - Removal of nitric oxide from flue gas using water-soluble iron(II)
      dithiocarbamates.

PMID- 22148616
TI  - Settling speeds of sewage sludge in seawater.

PMID- 22148617
TI  - Aerosol formation by the photooxidation of cyclohexene in the presence of
      nitrogen oxides.

PMID- 22148618
TI  - Sequential degradation of chlorophenols by photolytic and microbial treatment.

PMID- 22148619
TI  - A multi-sediment trap study on the temporal and spatial variability of polycyclic
      aromatic hydrocarbons and lead in an anthropogenic influenced archipelago.

PMID- 22148621
TI  - Humic acid complexation of calcium and copper.

PMID- 22148620
TI  - Polynuclear aromatic compounds and genotoxicity in particulate and vapor phases
      of ambient air:  effect of traffic, season, and meteorological conditions.

PMID- 22148622
TI  - Comment on "Estimation of effect of environmental tobacco smoke on air quality
      within passenger cabins of commercial aircraft".

PMID- 22148623
TI  - Reply to comment on "Estimation of effect of environmental tobacco smoke on air
      quality within passenger cabins of commercial aircraft".

PMID- 22148624
TI  - Influence of vapor-phase sorption and diffusion on the fate of trichloroethylene
      in an unsaturated aquifer system [Erratum to document cited in
      CA108(20):173160d].

PMID- 22148625
TI  - Electron energy-loss safe-dose limits for manganese valence measurements in
      environmentally relevant manganese oxides.
AB  - Manganese (Mn) oxides are among the strongest mineral oxidants in the environment
      and impose significant influence on mobility and bioavailability of redox-active
      substances, such as arsenic, chromium, and pharmaceutical products, through
      oxidation processes. Oxidizing potentials of Mn oxides are determined by Mn
      valence states (2+, 3+, 4+). In this study, the effects of beam damage during
      electron energy-loss spectroscopy (EELS) in the transmission electron microscope
      have been investigated to determine the "safe dose" of electrons. Time series
      analyses determined the safe dose fluence (electrons/nm(2)) for todorokite (10(6)
      e/nm(2)), acid birnessite (10(5)), triclinic birnessite (10(4)), randomly stacked
      birnessite (10(3)), and delta-MnO(2) (<10(3)) at 200 kV. The results show that
      meaningful estimates of the mean Mn valence can be acquired by EELS if proper
      care is taken.

PMID- 22148626
TI  - Capillary electrophoresis.

PMID- 22148627
TI  - Disentangling crystallographic inequivalence and crystallographic forms of L
      arginine by one- and two-dimensional solid-state NMR spectroscopy.
AB  - Overlapping (13)C or (15)N solid-state NMR spectra from crystallographically
      different forms of L-arginine hydrochloride can be separated by exploiting
      differential proton T(1) relaxation in conjunction with cross-polarization.
      Dipolar (13)C-(13)C and (15)N-(15)N two-dimensional correlation experiments
      reveal resonances belonging to crystallographically and magnetically inequivalent
      molecules.

PMID- 22148628
TI  - Light splitting in nanoporous gold and silver.
AB  - Nanoporous gold and silver exhibit strong, omnidirectional broad-band absorption
      in the far-field. Even though they consist entirely of gold or silver atoms,
      these materials appear black and dull, in great contrast with the familiar luster
      of continuous gold and silver. The nature of these anomalous optical
      characteristics is revealed here by combining nanoscale electron energy loss
      spectroscopy with discrete dipole and boundary element simulations. It is
      established that the strong broad-band absorption finds its origin in nanoscale
      splitting of light, with great local variations in the absorbed color. This
      nanoscale polychromaticity results from the excitation of localized surface
      plasmon resonances, which are imaged and analyzed here with deep sub-wavelength,
      nanometer spatial resolution. We demonstrate that, with this insight, it is
      possible to customize the absorbance and reflectance wavelength bands of thin
      nanoporous films by only tuning their morphology.

PMID- 22148629
TI  - Acid-induced degradation of phosphorescent dopants for OLEDs and its application
      to the synthesis of tris-heteroleptic iridium(III) bis-cyclometalated complexes.
AB  - Investigations of blue phosphorescent organic light emitting diodes (OLEDs) based
      on [Ir(2-(2,4-difluorophenyl)pyridine)(2)(picolinate)] (FIrPic) have pointed to
      the cleavage of the picolinate as a possible reason for device instability. We
      reproduced the loss of picolinate and acetylacetonate ancillary ligands in
      solution by the addition of Bronsted or Lewis acids. When hydrochloric acid is
      added to a solution of a [Ir(C^N)(2)(X^O)] complex (C^N = 2-phenylpyridine (ppy)
      or 2-(2,4-difluorophenyl)pyridine (diFppy) and X^O = picolinate (pic) or
      acetylacetonate (acac)), the cleavage of the ancillary ligand results in the
      direct formation of the chloro-bridged iridium(III) dimer [{Ir(C^N)(2)(MU
      Cl)}(2)]. When triflic acid or boron trifluoride are used, a source of chloride
      (here tetrabutylammonium chloride) is added to obtain the same chloro-bridged
      iridium(III) dimer. Then, we advantageously used this degradation reaction for
      the efficient synthesis of tris-heteroleptic cyclometalated iridium(III)
      complexes [Ir(C^N(1))(C^N(2))(L)], a family of cyclometalated complexes otherwise
      challenging to prepare. We used an iridium(I) complex, [{Ir(COD)(MU-Cl)}(2)], and
      a stoichiometric amount of two different C^N ligands (C^N(1) = ppy; C^N(2) =
      diFppy) as starting materials for the swift preparation of the chloro-bridged
      iridium(III) dimers. After reacting the mixture with acetylacetonate and
      subsequent purification, the tris-heteroleptic complex [Ir(ppy)(diFppy)(acac)]
      could be isolated with good yield from the crude containing as well the bis
      heteroleptic complexes [Ir(ppy)(2)(acac)] and [Ir(diFppy)(2)(acac)]. Reaction of
      the tris-heteroleptic acac complex with hydrochloric acid gives pure heteroleptic
      chloro-bridged iridium dimer [{Ir(ppy)(diFppy)(MU-Cl)}(2)], which can be used as
      starting material for the preparation of a new tris-heteroleptic iridium(III)
      complex based on these two C^N ligands. Finally, we use DFT/LR-TDDFT to
      rationalize the impact of the two different C^N ligands on the observed
      photophysical and electrochemical properties.

PMID- 22148630
TI  - Detection of nutrient elements and contamination by pesticides in spinach and
      rice samples using laser-induced breakdown spectroscopy (LIBS).
AB  - The laser-induced breakdown spectroscopy (LIBS) technique was applied to quantify
      nutrients (Mg, Ca, Na, and K) in spinach and rice and to discriminate pesticide
      contaminated products in a rapid manner. Standard reference materials (spinach
      leaves and unpolished rice flour) were used to establish a relationship between
      LIBS intensity and the concentration of each element (Mg, Ca, Na, and K) (i.e.,
      calibration line). The limits of detection (LODs) for Mg, Ca, Na, and K were
      found to be 29.63, 102.65, 36.36, and 44.46 mg/kg in spinach and 7.54, 1.76,
      4.19, and 6.70 mg/kg in unpolished rice, respectively. Concentrations of those
      nutrient elements present in spinach and unpolished rice from a local market were
      determined by using the calibration lines and compared with those measured with
      ICP-OES, showing good agreement. The data also suggested that the LIBS technique
      with the chemometric method (PLS-DA) could be a great tool to distinguish
      pesticide-contaminated samples from pesticide-free samples in a rapid manner even
      though they have similar elemental compositions. Misclassification rates were
      found to be 0 and 2% for clean spinach and pesticide-contaminated spinach,
      respectively, by applying the PLS-DA model established from the training set of
      data to predict the classes of test samples.

PMID- 22148631
TI  - Reductions of phosphine oxides and sulfides by perchlorosilanes: evidence for the
      involvement of donor-stabilized dichlorosilylene.
AB  - Hexachlorodisilane reduces phosphine oxides and sulfides to the corresponding
      phosphines with opposite stereoselectivities. Through quantum mechanical
      calculations, a new mechanistic picture is reported that explains these
      stereoselectivities. Phosphine oxides are shown to react via conventional
      phosphorane intermediates, but phosphine sulfides follow a dramatically different
      mechanism involving donor-stabilized SiCl(2).

PMID- 22148632
TI  - Enhanced photocurrent in engineered bacteriorhodopsin monolayer.
AB  - The integration of the transmembrane protein bacteriorhodopsin (BR) with man-made
      electrode surfaces has attracted a great deal of interest for some two decades or
      more and holds significant promise from the perspective of derived photoresponse
      or energy capture interfaces. Here we demonstrate that a novel and strategically
      engineered cysteine site (M163C) can be used to intimately and effectively couple
      delipidated BR to supporting metallic electrode surfaces. By virtue of the
      combined effects of the greater surface molecular density afforded by
      delipidation, and the vicinity of the electrostatic changes associated with
      proton pumping to the transducing metallic continuum, the resulting films
      generate a considerably greater photocurrent density on wavelength-selective
      illumination than previously achievable with monolayers of BR. Given the uniquely
      photoresponsive, wavelength-selective, and photostable characteristics of this
      protein, the work has implications for utilization in solar energy capture and
      photodetector devices.

PMID- 22148633
TI  - Organic electrodes based on grafted oligothiophene units in ultrathin, large-area
      molecular junctions.
AB  - Molecular junctions were fabricated with the combined use of electrochemistry and
      conventional CMOS tools. They consist of a 5-10 nm thick layer of oligo(1-(2
      bisthienyl)benzene) between two gold electrodes. The layer was grafted onto the
      bottom electrode using diazonium electroreduction, which yields a stable and
      robust gold-oligomer interface. The top contact was obtained by direct electron
      beam evaporation on the molecular layers through masks defined by electron-beam
      lithography. Transport mechanisms across such easily p-dopable layers were
      investigated by analysis of current density-voltage (J-V) curves. Application of
      a tunneling model led to a transport parameter (thickness of ~2.4 nm) that was
      not consistent with the molecular thickness measured using AFM (~7 nm).
      Furthermore, for these layers with thicknesses of 5-10 nm, asymmetric J-V curves
      were observed, with current flowing more easily when the grafted electrode was
      positively polarized. In addition, J-V experiments at two temperatures (4 and 300
      K) showed that thermal activation occurs for such polarization but is not
      observed when the bias is reversed. These results indicate that simple tunneling
      cannot describe the charge transport in these junctions. Finally, analysis of the
      experimental results in term of "organic electrode" and redox chemistry in the
      material is discussed.

PMID- 22148634
TI  - Easy synthesis of surface-tunable carbon-encapsulated magnetic nanoparticles:
      adsorbents for selective isolation and preconcentration of organic pollutants.
AB  - We have prepared core/shell structured carbon-encapsulated magnetic nanoparticles
      (CMNPs) with a simple method by using inorganic iron salt and glucose solution as
      precursor substance. The synthetic procedure does not require the use of organic
      solvents. We have utilized X-ray photoelectron spectroscopy, infrared
      spectroscopy, X-ray diffraction, and Raman analysis to examine the surface
      properties of CMNPs prepared at different temperature. The specific surface
      areas, magnetization and contents of graphitized carbon on carbon shell of CMNPs
      increase with heat treatment temperature. The obtained CMNPs are used to adsorb
      or preconcentrate bisphenol A (BPA), 4-n-nonylphenol (4-NP), 4-tert-octylphenol
      (4-OP), diethyl phthalate (DEP), dipropyl phthalate (DPP), dibutyl phthalate
      (DBP) dicyclohexyl phthalate (DCHP), dioctyl phthalate (DOP), sulfonamide,
      tetracyclines, and quinolones antibiotics organic compounds from water samples.
      The adsorption of analytes is mainly based on pi-pi stacking interaction,
      hydrophobic interaction and hydrogen bonds between analytes and graphitic carbon.
      As a result, the adsorption or extraction behaviors of CMNPs to analytes are
      controlled by the content of oxygen-containing species and graphitized carbon on
      carbon shell of CMNPs. CMNPs prepared at 200  degrees C have ample oxygen
      containing species (80%) on surface and favor the adsorption and extraction of
      quinolones antibiotics. CMNPs heated at 300-500  degrees C with the
      graphitization efficiency of carbon shell lower than 50% exhibit great
      preconcentration performance to BPA, 4-NP, 4-OP, DBP, DCHP, DOP, tetracyclines,
      and quinolones antibiotics. CMNPs prepared at 850  degrees C are highly
      graphitized (80%) and have strong adsorption affinity to all model analytes;
      however, they can quantitatively extract only highly polar sulfonamide
      antibiotics and moderately polar DEP, DPP because of hard desorption of other
      model analytes. We suggest that the appropriate adsorbent to certain organic
      contaminants can be obtained with this technique just by tuning the heat
      temperature without any post-treatment.

PMID- 22148635
TI  - Virtual screening data fusion using both structure- and ligand-based methods.
AB  - Virtual screening is widely applied in drug discovery, and significant effort has
      been put into improving current methods. In this study, we have evaluated the
      performance of compound ranking in virtual screening using five different data
      fusion algorithms on a total of 16 data sets. The data were generated by docking,
      pharmacophore search, shape similarity, and electrostatic similarity, spanning
      both structure- and ligand-based methods. The algorithms used for data fusion
      were sum rank, rank vote, sum score, Pareto ranking, and parallel selection. None
      of the fusion methods require any prior knowledge or input other than the results
      from the single methods and, thus, are readily applicable. The results show that
      compound ranking using data fusion improves the performance and consistency of
      virtual screening compared to the single methods alone. The best performing data
      fusion algorithm was parallel selection, but both rank voting and Pareto ranking
      also have good performance.

PMID- 22148636
TI  - Polyoxometalates paneling through {Mo2O2S2} coordination: cation-directed
      conformations and chemistry of a supramolecular hexameric scaffold.
AB  - The chemical system based on the [Mo(2)O(2)S(2)(OH(2))(6)](2+) aqua cation (noted
      L) and the trivacant [AsW(9)O(33)](9-) polyoxometalate (noted POM) has been
      investigated. Depending upon the ionic strength and the nature of the alkali
      cations, these complementary components assemble to yield three different
      architectures derived as hexamer (1), tetramer (2), and dimer (3). This series of
      clusters displays the same stoichiometry {POM(6)L(9)}(36-), {POM(4)L(6)}(24-),
      and {POM(2)L(3)}(12-) for 1, 2, and 3, respectively, and their conditions of
      formation differ mainly by the nature and the concentration of the alkali cation
      (from Li to Cs). Structural characterizations of 1 reveal a large hexameric
      supramolecular scaffold (about 25 A in diameter), which encloses a large internal
      hole (about 200 A(3)) filled by water molecules and alkali cations (Na(+) or
      K(+)). The hexameric scaffold 1 exhibits a rare flexibility property evidenced in
      the solid state by two distinct conformations, either eclipsed (1a) or staggered
      off (1b). Both conformations appear clearly separated by a large twist angle (~40
      degrees ) and depend mainly on the composition of the internal hole. Structure of
      anion 2 shows a tetrahedral arrangement where the four POM units and the six
      connecting {Mo(2)O(2)S(2)} linkers are located at the corners and at the edges,
      respectively. The structure of anion 3 corresponds to the simplest arrangement,
      described as a dimeric association of two POM units linked by three
      {Mo(2)S(2)O(2)} pillars. Stability of the hexameric scaffold has been
      investigated in solution by (183)W and (39)K NMR and by UV-vis, showing that
      stability of 1 depends strongly on the proportion of potassium ions, which
      interfere through host-guest exchange. Density functional methodology (DFT) has
      been applied to compute the geometries and energies of dimer (3), tetramer (2)
      and hexamer (1) based on {AsW(9)O(33)} (POM) and {Mo(2)O(2)S(2)} (L) units.
      Calculations tend to show that internal cations act as "glue" to maintain the POM
      units connected through the conformationally inward-directed {Mo(2)O(2)S(2)}
      linkers.

PMID- 22148637
TI  - Theoretical investigation of the electrochemical mechanism of water splitting on
      a titanium oxide cluster model.
AB  - The step-by-step electrochemical mechanism of water splitting by removal of
      protons and electrons is examined for the reaction of one and two water molecules
      on a Ti(2)O(4) cluster. Density functional theory (B3LYP) and coupled cluster
      single point calculations are employed to compute gas phase reaction energies.
      The polarizable continuum model (PCM) is utilized to calculate energies in the
      aqueous phase. Both neutral and alkaline media are considered. Proton and
      electron removal steps are generally found to be highly endothermic, with the
      exception of proton removal steps in alkaline medium. The effect of an external
      potential on reaction energies is considered. Oxygen-oxygen bonds form after the
      removal of only two electrons.

PMID- 22148638
TI  - Triply triggered doxorubicin release from supramolecular nanocontainers.
AB  - The synthesis of a supramolecular double hydrophilic block copolymer (DHBC) held
      together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent self
      assembly into micelles is described. This system is responsive to multiple
      external triggers including temperature, pH and the addition of a competitive
      guest. The supramolecular block copolymer assembly consists of poly(N
      isopropylacrylamide) (PNIPAAm) as a thermoresponsive block and
      poly(dimethylaminoethylmethacrylate) (PDMAEMA) as a pH-responsive block.
      Moreover, encapsulation and controlled drug release was demonstrated with this
      system using the chemotherapeutic drug doxorubicin (DOX). This triple stimuli
      responsive DHBC micelle system represents an evolution over conventional double
      stimuli-responsive covalent diblock copolymer systems and displayed a significant
      reduction in the viability of HeLa cells upon triggered release of DOX from the
      supramolecular micellar nanocontainers.

PMID- 22148639
TI  - Synthesis and characterization of wurtzite-phase copper tin selenide
      nanocrystals.
AB  - A new wurtzite phase of copper tin selenide (CTSe) was discovered, and the
      resulting nanocrystals were synthesized via a facile solution-phase method. The
      wurtzite CTSe nanocrystals were synthesized with dodecylamine and 1-dodecanethiol
      as coordinating solvents and di-tert-butyl diselenide ((t)Bu(2)Se(2)) as the
      selenium source. Specific reaction control (i.e., a combination of 1
      dodecanethiol with (t)Bu(2)Se(2)) was proven to be critical in order to obtain
      this new phase of CTSe, which was verified by powder X-ray diffraction and
      selected area electron diffraction. The wurtzite CTSe nanocrystals possess an
      optical and electrochemical band gap of 1.7 eV and display an electrochemical
      photoresponse indicative of a p-type semiconductor.

PMID- 22148641
TI  - Analysis of the palladium-catalyzed (aromatic)C-H bond metalation-deprotonation
      mechanism spanning the entire spectrum of arenes.
AB  - A comprehensive understanding of the C-H bond cleavage step by the concerted
      metalation-deprotonation (CMD) pathway is important in further development of
      cross-coupling reactions using different catalysts. Distortion-interaction
      analysis of the C-H bond cleavage over a wide range of (hetero)aromatics has been
      performed in an attempt to quantify the various contributions to the CMD
      transition state (TS). The (hetero)aromatics evaluated were divided in different
      categories to allow an easier understanding of their reactivity and to quantify
      activation characteristics of different arene substituents. The CMD pathway to
      the C-H bond cleavage for different classes of arenes is also presented,
      including the formation of pre-CMD intermediates and the analysis of bonding
      interactions in TS structures. The effects of remote C2 substituents on the
      reactivity of thiophenes were evaluated computationally and were corroborated
      experimentally with competition studies. We show that nucleophilicity of
      thiophenes, evaluated by Hammett sigma(p) parameters, correlates with each of the
      distortion-interaction parameters. In the final part of this manuscript, we set
      the initial equations that can assist in the development of predictive guidelines
      for the functionalization of C-H bonds catalyzed by transition metal catalysts.

PMID- 22148640
TI  - Rapid reaction kinetics of proline dehydrogenase in the multifunctional proline
      utilization A protein.
AB  - The multifunctional proline utilization A (PutA) flavoenzyme from Escherichia
      coli catalyzes the oxidation of proline to glutamate in two reaction steps using
      separate proline dehydrogenase (PRODH) and Delta(1)-pyrroline-5-carboxylate (P5C)
      dehydrogenase domains. Here, the kinetic mechanism of PRODH in PutA is studied by
      stopped-flow kinetics to determine microscopic rate constants for the
      proline:ubiquinone oxidoreductase mechanism. Stopped-flow data for proline
      reduction of the flavin cofactor (reductive half-reaction) and oxidation of
      reduced flavin by CoQ(1) (oxidative half-reaction) were best-fit by a double
      exponential from which maximum observable rate constants and apparent equilibrium
      dissociation constants were determined. Flavin semiquinone was not observed in
      the reductive or oxidative reactions. Microscopic rate constants for steps in the
      reductive and oxidative half-reactions were obtained by globally fitting the
      stopped-flow data to a simulated mechanism that includes a chemical step followed
      by an isomerization event. A microscopic rate constant of 27.5 s(-1) was
      determined for proline reduction of the flavin cofactor followed by an
      isomerization step of 2.2 s(-1). The isomerization step is proposed to report on
      a previously identified flavin-dependent conformational change [Zhang, W. et al.
      (2007) Biochemistry 46, 483-491] that is important for PutA functional switching
      but is not kinetically relevant to the in vitro mechanism. Using CoQ(1), a
      soluble analogue of ubiquinone, a rate constant of 5.4 s(-1) was obtained for the
      oxidation of flavin, thus indicating that this oxidative step is rate-limiting
      for k(cat) during catalytic turnover. Steady-state kinetic constants calculated
      from the microscopic rate constants agree with the experimental k(cat) and
      k(cat)/K(m) parameters.

PMID- 22148645
TI  - Editorial:  Cross-disciplinary research.

PMID- 22148646
TI  - Letters.

PMID- 22148643
TI  - Enhanced nuclear import and transfection efficiency of TAT peptide-based gene
      delivery systems modified by additional nuclear localization signals.
AB  - Cellular uptake and nuclear localization are two major barriers in gene delivery.
      In order to evaluate whether additional nuclear localization signals (NLSs) can
      improve gene transfection efficiency, we introduced different kinds of NLSs to
      TAT-based gene delivery systems to form three kinds of complexes, including TAT
      PV/DNA, TAT/DNA/PV, and TAT/DNA/HMGB1. The DNA binding ability of different
      vectors was evaluated by agarose gel electrophoresis. The in vitro transfections
      mediated by different complexes under different conditions were carried out. The
      cells treated by different complexes were observed by confocal microscopy. The
      MTT assay showed that all complexes did not exhibit apparent cytotoxicity in both
      HeLa and Cos7 cell lines even at high N/P ratios. The luciferase reporter gene
      expression mediated by TAT-PV/DNA complexes exhibited about 200-fold enhancement
      as compared with TAT/DNA complexes. Confocal study showed that, except
      TAT/DNA/PV, all other complexes exhibited enhanced nuclear accumulation and
      cellular uptake in both HeLa and Cos7 cell lines. These results indicated that
      the introduction of nuclear localization signals could enhance the transfection
      efficacy of TAT-based peptides, implying that the TAT peptide-based vectors
      demonstrated here have promising potential in gene delivery.

PMID- 22148647
TI  - Currents.

PMID- 22148648
TI  - Accidental input of pesticides into the Rhine River.

PMID- 22148649
TI  - Finland's environmental trends.

PMID- 22148651
TI  - Regulatory Focus: International environmental activities: The world is getting
      smaller.

PMID- 22148650
TI  - Waste minimization in the chemical industry.

PMID- 22148652
TI  - ES Books: Toxic Substances and Human Risk: Principles of Data Interpretation.

PMID- 22148653
TI  - ES Meetings.

PMID- 22148654
TI  - Kinetic studies of cadmium and ferricyanide adsorption of goethite.

PMID- 22148655
TI  - Atmospheric chemistry of aldehydes:  enhanced peroxyacetyl nitrate formation from
      ethanol-fueled vehicular emissions.

PMID- 22148656
TI  - In situ comparison of a multistage series cyclone system and a cascade impactor
      for in-stack dust sampling.

PMID- 22148657
TI  - Avian tissues as bioindicators of exposure to alkylleads:  metabolism of
      ethyllead salts by Japanese quail.

PMID- 22148658
TI  - Nitration of acephenanthrylene under simulated atmospheric conditions and in
      solution and the presence of nitroacephenanthrylene(s) in ambient particles.

PMID- 22148659
TI  - Reactivities of hypochlorous and hypobromous acid, chlorine monoxide, hypobromous
      acidium ion, chlorine, bromine, and bromine chloride in electrophilic aromatic
      substitution reactions with p-xylene in water.

PMID- 22148660
TI  - A kinetic model for the halogenation of p-xylene in aqueous hypochlorous acid
      solutions containing chloride and bromide.

PMID- 22148661
TI  - Organochlorine contaminants in arctic marine food chains:  identification,
      geographical distribution and temporal trends in polar bears.

PMID- 22148662
TI  - Organochlorine contaminants in arctic marine food chains:  accumulation of
      specific polychlorinated biphenyls and chlordane-related compounds.

PMID- 22148663
TI  - Vapor-phase concentrations of arsenic, selenium, bromine, iodine, and mercury in
      the stack of a coal-fired power plant.

PMID- 22148664
TI  - Studies of the diurnal variation of nitrous acid in urban air.

PMID- 22148665
TI  - Mechanisms for aqueous photolysis of adsorbed benzoate, oxalate, and succinate on
      iron oxyhydroxide (goethite) surfaces.

PMID- 22148666
TI  - Identification and quantification of the Ames mutagenic compound 3-chloro-4
      (dichloromethyl)-5-hydroxy-2(5H)-furanone and of its geometric isomer (E)-2
      chloro-3-(dichloromethyl)-4-oxobutenoic acid in chlorine-treated humic water and
      drinking water extracts.

PMID- 22148667
TI  - Total organic carbon concentrations in acidic lakes in southern Norway.

PMID- 22148668
TI  - Measurement of aqueous aluminum species:  comparison of dialysis and ion-exchange
      techniques.

PMID- 22148669
TI  - Indoor particle concentrations associated with use of tap water in portable
      humidifiers.

PMID- 22148670
TI  - Manganese carbonyls bearing tripodal polypyridine ligands as photoactive carbon
      monoxide-releasing molecules.
AB  - The recently discovered cytoprotective action of CO has raised interest in
      exogenous CO-releasing materials (CORMs) such as metal carbonyls (CO complexes of
      transition metals). To achieve control on CO delivery with metal carbonyls, we
      synthesized and characterized three Mn(I) carbonyls, namely,
      [Mn(tpa)(CO)(3)]ClO(4) [1, where tpa = tris(2-pyridyl)amine], [Mn(dpa)(CO)(3)]Br
      [2, where dpa = N,N-bis(2-pyridylmethyl)amine], and [Mn(pqa)(CO)(3)]ClO(4) [3,
      where pqa = (2-pyridylmethyl)(2-quinolylmethyl)amine], by crystallography and
      various spectroscopic techniques. All three carbonyls are sensitive to light and
      release CO when illuminated with low-power UV (5-10 mW) and visible (lambda > 350
      nm, ~100 mW) light. The sensitivity of 1-3 to light has been assessed with
      respect to the number of pyridine groups in their ligand frames. When a pyridine
      ring is replaced with quinoline, extended conjugation in the ligand frame
      increases the absorptivity and makes the resulting carbonyl 3 more sensitive to
      visible light. These photosensitive CORMs (photoCORMs) have been employed to
      deliver CO to myoglobin under the control of light. The superior stability of 3
      in aqueous media makes it a photoCORM suitable for inducing vasorelaxation in
      mouse aortic muscle rings.

PMID- 22148671
TI  - Anisotropic wetting of microstructured surfaces as a function of surface
      chemistry.
AB  - In order to study the influence of surface chemistry on the wetting of structured
      surfaces, microstructures consisting of grooves or squares were produced via hot
      embossing of poly(ethylene-alt-tetrafluoroethylene) ETFE substrates. The
      structured substrates were modified with polymer brushes, thereby changing their
      surface functionality and wettability. Water droplets were most strongly pinned
      to the structure when the surface was moderately hydrophilic, as in the case of
      poly(4-vinylpyridine) (P4VP) or poly(vinyl(N-methyl-2-pyridone) (PVMP) brush
      modified substrates. As a result, the droplet shape was determined by the
      features of the microstructure. The water contact angles (CA) were considerably
      higher than on flat surfaces and differed, in the most extreme case, by 37
      degrees  when measured on grooved substrates, parallel and perpendicular to the
      grooves. On hydrophobic substrates (pristine ETFE), the same effects were
      observed but were much less pronounced. On very hydrophilic sampes (those
      modified with poly(N-methyl-vinylpyridinium) (QP4VP)), the microstructure had no
      influence on the drop shape. These findings are explained by significant
      differences in apparent and real contact angles at the relatively smooth edges of
      the embossed structures. Finally, the highly anisotropic grooved microstructure
      was combined with a gradient in polymer brush composition and wettability. In the
      case of a parallel alignment of the gradient direction to the grooves, the
      directed spreading of water droplets could be observed.

PMID- 22148672
TI  - Acetylcholinesterase liquid crystal biosensor based on modulated growth of gold
      nanoparticles for amplified detection of acetylcholine and inhibitor.
AB  - A novel acetylcholinesterase (AChE) liquid crystal (LC) biosensor based on
      enzymatic growth of gold nanoparticles (Au NPs) has been developed for amplified
      detection of acetylcholine (ACh) and AChE inhibitor. In this method, AChE
      mediates the hydrolysis of acetylthiocholine (ATCl) to form thiocholine, and the
      latter further reduces AuCl(4)(-) to Au NPs without Au nanoseeds. This process,
      termed biometallization, leads to a great enhancement in the optical signal of
      the LC biosensor due to the large size of Au NPs, which can greatly disrupt the
      orientational arrangement of LCs. On the other hand, the hydrolysis of ATCl is
      inhibited in the presence of ACh or organophosphate pesticides (OPs, a AChE
      inhibitor), which will decrease the catalytic growth of Au NPs and, as a result,
      reduce the orientational response of LCs. On the basis of such an inhibition
      mechanism, the AChE LC biosensor can be used as an effective way to realize the
      detection of ACh and AChE inhibitors. The results showed that the AChE LC
      biosensor was highly sensitive to ACh with a detection limit of 15 MUmol/L and
      OPs with a detection limit of 0.3 nmol/L. This study provides a simple and
      sensitive AChE LC biosensing approach and offers effective signal enhanced
      strategies for the development of enzyme LC biosensors.

PMID- 22148673
TI  - Design of combinatorial libraries for the exploration of virtual hits from
      fragment space searches with LoFT.
AB  - A case study is presented illustrating the design of a focused CDK2 library. The
      scaffold of the library was detected by a feature trees search in a fragment
      space based on reactions from combinatorial chemistry. For the design the
      software LoFT (Library optimizer using Feature Trees) was used. The special
      feature called FTMatch was applied to restrict the parts of the queries where the
      reagents are permitted to match. This way a 3D scoring function could be
      simulated. Results were compared with alternative designs by GOLD docking and
      ROCS 3D alignments.

PMID- 22148674
TI  - Nanomechanical recognition of sphingomyelin-rich membrane domains by atomic force
      microscopy.
AB  - Sphingomyelin (SM) is a reservoir of signaling lipids and forms specific lipid
      domains in biomembranes together with cholesterol. In this study, atomic force
      microscopy (AFM) and force measurement were applied to investigate the
      interaction of SM-binding protein toxin, lysenin, with N-palmitoyl-D-erythro
      sphingosylphosphorylcholine (palmitoyl sphingomyelin, PSM) bilayer spread over a
      mica substrate, in an aqueous buffer solution. Lysenin molecules were grafted on
      a silicon nitride tip for AFM by siloxane-thiol-amide coupling. The bilayers were
      prepared by the Langmuir-Blodgett (LB)/Langmuir-Schaefer (LS) method. By
      repeating cycles of tip approach/retraction motion, single-molecular adhesion
      motions were observed on the force curve, characterized as "fishing curves". The
      addition of cholesterol and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) did
      not alter the peak force but increased the peak extension. Mixtures of
      PSM/DOPC/cholesterol exhibited 2-dimensional two-phase domain separation. The
      characteristic fishing curves were observed exclusively in one of the phases,
      indicating the selective interaction of the lysenin tip to PSM-rich membrane
      domains. Our results indicate that the AFM tips conjugated with lysenin are
      useful to detect the surface distribution of SM-rich membrane domains as well as
      the nanomechanical properties of the domains.

PMID- 22148675
TI  - Iridium-catalyzed addition of aroyl chlorides and aliphatic acid chlorides to
      terminal alkynes.
AB  - Iridium complexes show high catalytic activity in intermolecular additions of
      acid chlorides to terminal alkynes to afford valuable (Z)-beta-chloro-alpha,beta
      unsaturated ketones. Ligands in the catalytic system play a crucial role in this
      reaction. An N-heterocyclic carbene (NHC) is an efficient ligand for the addition
      of aroyl chlorides, while dicyclohexyl(2-methylphenyl)phosphine (PCy(2)(o-Tol))
      is indispensable for the reaction of aliphatic acid chlorides. The addition
      reactions proceed regio- and stereoselectively with suppression of
      decarbonylation and beta-hydrogen elimination, which have been two major
      intrinsic problems in transition-metal-catalyzed reactions. Stoichiometric
      reactions of active iridium catalysts with aroyl chlorides and aliphatic acid
      chlorides are carried out to gain insights into the reaction mechanisms.

PMID- 22148676
TI  - Diffusion of a spherical probe through static nematogens: effect of increasing
      geometric anisotropy and long-range structure.
AB  - Diffusional behavior of a spherical probe through static nematogens (or needles)
      is probed via molecular dynamics simulations. The needles are modeled as
      spherocylinders and are arranged in idealized limits of an isotropic phase and a
      slowly quenched nematic mesh. The spherical probe exhibits superdiffusive motion
      through both the isotropic and nematic scatterer configurations. The
      superdiffusive behavior results from directional collisions between the spherical
      probe and the static nematogens. Velocity autocorrelation functions show long
      time correlations caused by directionality of transport due to the geometric
      anisotropy of the scatterers; however, glassy behavior exhibited by the tracer is
      observed when the scatterers are sufficiently long, leading to a downturn in the
      diffusion coefficients. Diffusion through the nematic configuration shows
      anisotropic diffusion with preferential motion occurring along the orientational
      director by way of effective channels formed by the long-range orientational
      order of the aligned nematogens.

PMID- 22148677
TI  - Wafer-scale fabrication and characterization of thin-film transistors with
      polythiophene-sorted semiconducting carbon nanotube networks.
AB  - Semiconducting single-walled carbon nanotubes (SWCNTs) have great potential of
      becoming the channel material for future thin-film transistor technology.
      However, an effective sorting technique is needed to obtain high-quality
      semiconducting SWCNTs for optimal device performance. In our previous work, we
      reported a dispersion technique for semiconducting SWCNTs that relies on
      regioregular poly(3-dodecylthiophene) (rr-P3DDT) to form hybrid nanostructures.
      In this study, we demonstrate the scalability of those sorted CNT composite
      structures to form arrays of TFTs using standard lithographic techniques. The
      robustness of these CNT nanostructures was tested with Raman spectroscopy and
      atomic force microscope images. Important trends in device properties were
      extracted by means of electrical measurements for different CNT concentrations
      and channel lengths (L(c)). A statistical study provided an average mobility of 1
      cm(2)/V.s and I(on)/I(off) as high as 10(6) for short channel lengths (L(c) = 1.5
      MUm) with 100% yield. This highlights the effectiveness of this sorting technique
      and its scalability for large-scale, flexible, and transparent display
      applications.

PMID- 22148678
TI  - Applicability of plasmid calibrant pTC1507 in quantification of TC1507 maize: an
      interlaboratory study.
AB  - To enforce the labeling regulations of genetically modified organisms (GMOs), the
      application of DNA plasmids as calibrants is becoming essential for the practical
      quantification of GMOs. This study reports the construction of plasmid pTC1507
      for a quantification assay of genetically modified (GM) maize TC1507 and the
      collaborative ring trial in international validation of its applicability as a
      plasmid calibrant. pTC1507 includes one event-specific sequence of TC1507 maize
      and one unique sequence of maize endogenous gene zSSIIb. A total of eight GMO
      detection laboratories worldwide were invited to join the validation process, and
      test results were returned from all eight participants. Statistical analysis of
      the returned results showed that real-time PCR assays using pTC1507 as calibrant
      in both GM event-specific and endogenous gene quantifications had high PCR
      efficiency (ranging from 0.80 to 1.15) and good linearity (ranging from 0.9921 to
      0.9998). In a quantification assay of five blind samples, the bias between the
      test values and true values ranged from 2.6 to 24.9%. All results indicated that
      the developed pTC1507 plasmid is applicable for the quantitative analysis of
      TC1507 maize and can be used as a suitable substitute for dried powder certified
      reference materials (CRMs).

PMID- 22148679
TI  - Single-wing extended tribenzotriquinacenes via bowl-shaped dehydrobenzene and
      isobenzofuran tribenzotriquinacene derivatives.
AB  - Monoaryne and monoisobenzofuran analogues of a C(3v)-symmetrical
      tribenzotriquinacene (TBTQ) were generated in situ and trapped with various
      dienes and dienophiles, respectively. In this way, a series of single-wing
      extended TBTQ derivatives bearing the bowl-shaped TBTQ unit in different
      topographical expositions have become accessible. This includes some novel
      tribenzotriquinacene "dimers", in which two TBTQ bowls are attached in syn- or
      anti-orientation at the terminal positions of rigid linker units. Several of
      these compounds have been characterized by both spectroscopy and X-ray structural
      analysis. The efficient access to the TBTQ "dimers" may lay a useful foundation
      for further studies of novel container compounds and supramolecular
      architectures.

PMID- 22148680
TI  - Theoretical investigation of the reaction of Mn+ with ethylene oxide.
AB  - The potential energy surfaces of Mn(+) reaction with ethylene oxide in both the
      septet and quintet states are investigated at the B3LYP/DZVP level of theory. The
      reaction paths leading to the products of MnO(+), MnO, MnCH(2)(+), MnCH(3), and
      MnH(+) are described in detail. Two types of encounter complexes of Mn(+) with
      ethylene oxide are formed because of attachments of the metal at different sites
      of ethylene oxide, i.e., the O atom and the CC bond. Mn(+) would insert into a C
      O bond or the C-C bond of ethylene oxide to form two different intermediates
      prior to forming various products. MnO(+)/MnO and MnH(+) are formed in the C-O
      activation mechanism, while both C-O and C-C activations account for the
      MnCH(2)(+)/MnCH(3) formation. Products MnO(+), MnCH(2)(+), and MnH(+) could be
      formed adiabatically on the quintet surface, while formation of MnO and MnCH(3)
      is endothermic on the PESs with both spins. In agreement with the experimental
      observations, the excited state a(5)D is calculated to be more reactive than the
      ground state a(7)S. This theoretical work sheds new light on the experimental
      observations and provides fundamental understanding of the reaction mechanism of
      ethylene oxide with transition metal cations.

PMID- 22148681
TI  - Artificial light-harvesting arrays: electronic energy migration and trapping on a
      sphere and between spheres.
AB  - A sophisticated model of the natural light-harvesting antenna has been devised by
      decorating a C(60) hexa-adduct with ten yellow and two blue boron dipyrromethene
      (Bodipy) dyes in such a way that the dyes retain their individuality and assist
      solubility of the fullerene. Unusually, the fullerene core is a poor electron
      acceptor and does not enter into light-induced electron-transfer reactions with
      the appended dyes, but ineffective electronic energy transfer from the excited
      state dye to the C(60) residue competes with fluorescence from the yellow dye.
      Intraparticle electronic energy transfer from yellow to blue dyes can be followed
      by steady-state and time-resolved fluorescence spectroscopy and by excitation
      spectra for isolated C(60) nanoparticles dissolved in dioxane at 293 K and at 77
      K. The decorated particles can be loaded into polymer films by spin coating from
      solution. In the dried film, efficient energy transfer occurs such that photons
      absorbed by the yellow dye are emitted by the blue dye. Films can also be
      prepared to contain C(60) nanoparticles loaded with the yellow Bodipy dye but
      lacking the blue dye and, under these circumstances, electronic energy migration
      occurs between yellow dyes appended to the same nanoparticle and, at higher
      loading, to dye molecules on nearby particles. Doping these latter polymer films
      with the mixed-dye nanoparticle coalesces these multifarious processes in a
      single system. Thus, long-range energy migration occurs among yellow dyes
      attached to different particles before trapping at a blue dye. In this respect,
      the film resembles the natural photosynthetic light-harvesting complexes, albeit
      at much reduced efficacy. The decorated nanoparticles sensitize amorphous silicon
      photocells.

PMID- 22148683
TI  - Preparation and characterization of imogolite/DNA hybrid hydrogels.
AB  - Imogolite is one of the clay minerals contained in volcanic ash soils. The novel
      hybrid hydrogels were prepared from imogolite nanofibers and DNA by utilizing
      strong interaction between the aluminol groups on imogolite surface and phosphate
      groups of DNA. The hybrid hydrogels of imogolite and DNA were prepared in various
      feed ratios, and their physicochemical properties and molecular aggregation
      states were investigated in both dispersion and gel states. The maximum DNA
      content in the hybrid gels was shown in equivalent molar ratio of imogolite and
      DNA. The physical properties of the hybrid gels were changed by varying DNA blend
      ratios. In the dispersion state, the hybrid gels showed a fibrous structure of
      imogolite, whereas a continuous network structure was observed in pure imogolite,
      indicating that the hybrid with DNA enhanced the dispersion of imogolite. In the
      gel state, DNA and imogolite nanofibers formed a 3D network structure.

PMID- 22148686
TI  - Editorial.  Water cleanup strategies.

PMID- 22148687
TI  - Letters. Offshore drilling.

PMID- 22148684
TI  - Anisotropic organization and microscopic manipulation of self-assembling
      synthetic porphyrin microrods that mimic chlorosomes: bacterial light-harvesting
      systems.
AB  - Being able to control in time and space the positioning, orientation, movement,
      and sense of rotation of nano- to microscale objects is currently an active
      research area in nanoscience, having diverse nanotechnological applications. In
      this paper, we demonstrate unprecedented control and maneuvering of rod-shaped or
      tubular nanostructures with high aspect ratios which are formed by self
      assembling synthetic porphyrins. The self-assembly algorithm, encoded by appended
      chemical-recognition groups on the periphery of these porphyrins, is the same as
      the one operating for chlorosomal bacteriochlorophylls (BChl's). Chlorosomes, rod
      shaped organelles with relatively long-range molecular order, are the most
      efficient naturally occurring light-harvesting systems. They are used by green
      photosynthetic bacteria to trap visible and infrared light of minute intensities
      even at great depths, e.g., 100 m below water surface or in volcanic vents in the
      absence of solar radiation. In contrast to most other natural light-harvesting
      systems, the chlorosomal antennae are devoid of a protein scaffold to orient the
      BChl's; thus, they are an attractive goal for mimicry by synthetic chemists, who
      are able to engineer more robust chromophores to self-assemble. Functional
      devices with environmentally friendly chromophores-which should be able to act as
      photosensitizers within hybrid solar cells, leading to high photon-to-current
      conversion efficiencies even under low illumination conditions-have yet to be
      fabricated. The orderly manner in which the BChl's and their synthetic
      counterparts self-assemble imparts strong diamagnetic and optical anisotropies
      and flow/shear characteristics to their nanostructured assemblies, allowing them
      to be manipulated by electrical, magnetic, or tribomechanical forces.

PMID- 22148689
TI  - Currents.

PMID- 22148688
TI  - Letters.  Ozone correction.

PMID- 22148690
TI  - Outlook.

PMID- 22148691
TI  - PAT Report:  The aerial photo - water quality link.

PMID- 22148692
TI  - Earthwatching on a macro scale.

PMID- 22148693
TI  - Legal decisions and opinions in pollution cases.

PMID- 22148694
TI  - Coast Guards response to spilled oil.

PMID- 22148695
TI  - Preliminary small-scale combustion tests of coal liquids.

PMID- 22148696
TI  - Test of the theory of ozone generation in Los Angeles atmosphere.

PMID- 22148697
TI  - Hydrocarbon involvement in photochemical smog formation in Los Angeles
      atmosphere.

PMID- 22148698
TI  - Kinetics of limestone neutralization of acid waters.

PMID- 22148699
TI  - Records of lead deposition in Lake Michigan sediments since 1800.

PMID- 22148701
TI  - Continuous determination of free cyanide in effluents using silver ion selective
      electrode.

PMID- 22148700
TI  - Diffusive collection of aerosol particles on Nuclepore membrane filter.

PMID- 22148702
TI  - Transport of atmospheric sea salt in coastal zone.

PMID- 22148703
TI  - Trace elements in corn grown on long-term sludge disposal site.  Comments.

PMID- 22148704
TI  - Characterization of Australian crudes and condensates by gas chromatographic
      analysis.  Reply to comments.

PMID- 22148705
TI  - Characterization of Australian crudes and condensates by gas chromatographic
      analysis.  Comments.

PMID- 22148706
TI  - Trace elements in corn grown on long-term sludge disposal site.  Reply to
      comments.

PMID- 22148707
TI  - Industry trends.

PMID- 22148709
TI  - New literature.

PMID- 22148711
TI  - New ternary germanides La4Mg5Ge6 and La4Mg7Ge6: crystal structure and chemical
      bonding.
AB  - The synthesis, structural characterization, and chemical-bonding peculiarities of
      the two new polar lanthanum-magnesium germanides La(4)Mg(5)Ge(6) and
      La(4)Mg(7)Ge(6) are reported. The crystal structures of these intermetallics were
      determined by single-crystal X-ray diffraction analysis. The La(4)Mg(5)Ge(6)
      phase crystallizes in the orthorhombic Gd(4)Zn(5)Ge(6) structure type [Cmc2(1),
      oS60, Z = 4, a = 4.5030(7) A, b = 20.085(3) A, c = 16.207(3) A, wR2 = 0.0451,
      1470 F(2) values, 93 variables]. The La(4)Mg(7)Ge(6) phase represents a new
      structure type with a monoclinic unit cell [C2/m, mS34, Z = 2, a = 16.878(3) A, b
      = 4.4702(9) A, c = 12.660(3) A, beta = 122.25(3) degrees , wR2 = 0.0375, 1466
      F(2) values, 54 variables]. Crystallographic analysis together with linear muffin
      tin orbital band structure calculations reveals the presence of strongly bonded
      3D polyanionic [Mg-Ge] networks balanced by positively charged La atoms in both
      stoichiometric compounds. The La(4)Mg(5)Ge(6) compound is related to Zintl
      phases, showing a prominent density of states pseudogap at the Fermi level. A
      distinctive feature of the La(4)Mg(5)Ge(6) structure is the presence of Ge-Ge
      covalent dumbbells; in La(4)Mg(7)Ge(6), the higher Mg content generates a
      polyanionic network consisting exclusively of Mg-Ge heterocontacts. Nevertheless,
      the frameworks of the two phases are structurally similar, as is highlighted in
      this work.

PMID- 22148713
TI  - Structure and magnetism in Fe-Gd based dinuclear and chain systems. The interplay
      of weak exchange coupling and zero field splitting effects.
AB  - The synthesis and characterization of two Fe-Gd systems based on bpca(-) (Hbpca =
      bis(2-pyridilcarbonyl)amine) as bridging ligand is presented, taking the systems
      as a case study for structure-property correlations. Compound 1, [Fe(LS)(II)(MU
      bpca)(2)Gd(NO(3))(2)(H(2)O)]NO(3).2CH(3)NO(2), is a zigzag polymer, incorporating
      the diamagnetic low spin Fe(LS)(II) ion. The magnetism of 1 is entirely
      determined by the weak zero field splitting (ZFS) effect on the Gd(III) ion.
      Compound 2 is a Fe(III)-Gd(III) dinuclear compound, [Fe(LS)(III)(bpca)(MU
      bpca)Gd(NO(3))(4)].4CH(3)NO(2).CH(3)OH, its magnetism being interpreted as due to
      the antiferromagnetic coupling between the S(Fe) = 1/2 and S(Gd) = 7/2 spins,
      interplayed with the local ZFS on the lanthanide center. In both systems, the d-f
      assembly is determined by the bridging capabilities of the ambidentate bpca(-)
      ligand, which binds the d ion by a tridentate moiety with nitrogen donors and the
      f center by the diketonate side. We propose a spin delocalization and
      polarization mechanism that rationalizes the factors leading to the
      antiferromagnetic d-f coupling. Although conceived for compound 2, the scheme can
      be proposed as a general mechanism. The rationalization of the weak ZFS effects
      on Gd(III) by multiconfiguration and spin-orbit ab initio calculations allowed us
      to determine the details of the small but still significant anisotropy of Gd(III)
      ion in the coordination sites of compounds 1 and 2. The outlined methodologies
      and generalized conclusions shed new light on the field of gadolinium
      coordination magnetochemistry.

PMID- 22148714
TI  - Creating self-organized submicrometer contact instability patterns in soft
      elastic bilayers with a topographically patterned stamp.
AB  - The surface of a thin elastic bilayer becomes spontaneously unstable when it is
      brought in proximity to another rigid contactor. The instability patterns, which
      are random and isotropic, exhibit a dominant lateral length scale of instability
      lambda, which linearly scales with the bilayer thickness (h) as: lambda = R(F)h.
      It is known that for an elastic bilayer, R(F) exhibits a nonlinear dependence on
      the ratios of individual film thicknesses (H) and shear moduli (M) of the two
      constituent layers, and can have values as low as 0.5 under specific conditions.
      This is in contrast to a near constant value of R(F) ~ 3 for a single layer
      elastic film. (1) These isotropic contact instability patterns in a bilayer can
      be ordered, aligned and modulated using a topographically patterned stamp. The
      precise morphology of the aligned structures depends on commensuration between
      lambda and the stamp periodicity (lambda(P)), and on the intersurface separation
      distance. A variety of patterns, like an array of circular holes, double periodic
      channels, etc., in addition to a positive and a negative replica of the stamp
      pattern, can be engineered with a simple stamp having 1D grating structure. A
      lower value of R(F) in a bilayer allows generating patterns with sub 500 nm
      lateral resolution, which is impossible to create by elastic contact lithography
      (ECL) of a single layer film due to strong surface tension effects in ultrathin
      films. Thus, control of elastic instability in a bilayer with a patterned stamp
      represents a flexible soft lithography tool allowing modulation of length scales,
      morphology, and order.

PMID- 22148715
TI  - Femtosecond photodynamics of the red/green cyanobacteriochrome NpR6012g4 from
      Nostoc punctiforme. 1. Forward dynamics.
AB  - Phytochromes are well-known red/far-red photosensory proteins that utilize the
      photoisomerization of a linear tetrapyrrole (bilin) chromophore to detect the
      ratio of red to far-red light. Cyanobacteriochromes (CBCRs) are related
      photosensory proteins with a bilin-binding GAF domain, but much more diverse
      spectral sensitivity, with five recognized subfamilies of CBCRs described to
      date. The mechanisms that underlie this spectral diversity have not yet been
      fully elucidated. One of the main CBCR subfamilies photoconverts between a red
      absorbing ground state, like the familiar P(r) state of phytochromes, and a green
      absorbing photoproduct (P(g)). Here, we examine the ultrafast forward
      photodynamics of the red/green CBCR NpR6012g4 from the NpR6012 locus of the
      nitrogen-fixing cyanobacterium Nostoc punctiforme. Using transient absorption
      spectroscopy with broadband detection and multicomponent global analysis, we
      observed multiphasic excited-state dynamics that induces the forward reaction
      (red-absorbing to green-absorbing), which we interpret as arising from ground
      state heterogeneity. Excited-state decays with lifetimes of 55 and 345 ps
      generate the primary photoproduct (Lumi-R), and the fastest decay (5 ps) did not
      produce Lumi-R. Although the photoinduced kinetics of Npr6012g4 is comparable
      with that of the Cph1 phytochrome isolated from Synechocystis cyanobacteria,
      NpR6012g4 exhibits a >=2-3-fold higher photochemical quantum yield. Understanding
      the structural basis of this enhanced quantum yield may prove to be useful in
      increasing the photochemical efficiency of other bilin-based photosensors.

PMID- 22148716
TI  - Validation of paper-based assay for rapid blood typing.
AB  - We developed and validated a new paper-based assay for the detection of human
      blood type. Our method involves spotting a 3 MUL blood sample on a paper surface
      where grouping antibodies have already been introduced. A thin film chromatograph
      tank was used to chromatographically elute the blood spot with 0.9% NaCl buffer
      for 10 min by capillary absorption. Agglutinated red blood cells (RBCs) were
      fixed on the paper substrate, resulting in a high optical density of the spot,
      with no visual trace in the buffer wicking path. Conversely, nonagglutinated RBCs
      could easily be eluted by the buffer and had low optical density of the spot and
      clearly visible trace of RBCs in the buffer wicking path. Different paper
      substrates had comparable ability to fix agglutinated blood, while a more porous
      substrate like Kleenex paper had enhanced ability to elute nonagglutinated blood.
      Using optimized conditions, a rapid assay for detection of blood groups was
      developed by spotting blood to antibodies absorbed to paper and eluted with 200
      MUL of 0.9% NaCl buffer directly by pipetting. RBCs fixation on paper accurately
      detected blood groups (ABO and RhD) using ascending buffer for 10 min or using a
      rapid elution step in 100/100 blood samples including 4 weak AB and 4 weak RhD
      samples. The assay has excellent reproducibility where the same blood group was
      obtained in 26 samples assessed in 2 different days. Agglutinated blood fixation
      on porous paper substrate provides a new, simple, and sensitive assay for rapid
      detection of blood group for point-of-care applications.

PMID- 22148717
TI  - Improved chemical text mining of patents with infinite dictionaries and automatic
      spelling correction.
AB  - The text mining of patents of pharmaceutical interest poses a number of unique
      challenges not encountered in other fields of text mining. Unlike fields, such as
      bioinformatics, where the number of terms of interest is enumerable and
      essentially static, systematic chemical nomenclature can describe an infinite
      number of molecules. Hence, the dictionary- and ontology-based techniques that
      are commonly used for gene names, diseases, species, etc., have limited utility
      when searching for novel therapeutic compounds in patents. Additionally, the
      length and the composition of IUPAC-like names make them more susceptible to
      typographic problems: OCR failures, human spelling errors, and hyphenation and
      line breaking issues. This work describes a novel technique, called CaffeineFix,
      designed to efficiently identify chemical names in free text, even in the
      presence of typographical errors. Corrected chemical names are generated as input
      for name-to-structure software. This forms a preprocessing pass, independent of
      the name-to-structure software used, and is shown to greatly improve the results
      of chemical text mining in our study.

PMID- 22148718
TI  - Titanium(IV)-promoted regioselective nucleophilic ring-opening reaction of chiral
      epoxyallyl alcohols with acids as a tool for ready access to chiral 1,2,3-triol
      monoesters: application to stereoselective total synthesis of macrolides.
AB  - Titanium(IV)-promoted regioselective ring-opening reaction of chiral epoxy-allyl
      alcohols (Sharpless conditions as the key strategic step) is developed as a tool
      for ready access to chiral 5,6-dihydroxyoct-7-en-4-yl alkoxylates. Later, the
      synthetic utility of products thereof was demonstrated through the RCM based
      stereoselective synthesis of various natural products.

PMID- 22148719
TI  - Conformational study of the hydroxyproline-O-glycosidic linkage: sugar-peptide
      orientation and prolyl amide isomerization in (alpha/beta)-galactosylated 4(R/S)
      hydroxyproline.
AB  - Glycosylation is a frequent post-translational modification of proteins that has
      been shown to influence protein structure and function. Glycosylation of
      hydroxyproline occurs widely in plants, but is absent in humans and animals.
      Previous experimental studies on model amides have indicated that alpha/beta
      galactosylation of 4R-hydroxyproline (Hyp) has no measurable effect on prolyl
      amide isomerization, while a 7% increase in the trans isomer population, as well
      as a 25-50% increase in the isomerization rate, was observed for the 4S
      stereoisomer (hyp). In this work, molecular dynamics simulations in explicit
      water and implicit solvent DFT optimizations are used to examine the structure of
      the hydroxyproline-O-galactosyl linkage and the effect of glycosylation on the
      structure and cis/trans isomerization of the peptide backbone. The calculations
      show two major minima with respect to the glycosidic linkage in all compounds.
      The C(gamma)-exo puckering observed in 4R compounds projects the sugar away from
      the peptide backbone, while a twisted C(gamma)-endo/C(beta)-exo pucker in the 4S
      compounds brings the peptide and sugar rings together and leads to an
      intramolecular hydrogen-bonding interaction that is sometimes bridged by a water
      molecule. This hydrogen bond changes the conformation of the peptide backbone,
      inducing a favorable n -> pi* interaction between the oxygen lone pair from the
      prolyl N-terminal amide and the C?O, which explains the observed increase in
      trans isomer population in alpha/beta-galactosylated 4S-hydroxyproline. Our
      results provide the first molecular level information about this important
      glycosidic linkage, as well as provide an explanation for the previously observed
      increase in trans isomer population in 4S-hyp compounds. Moreover, this study
      provides evidence that sugar-mediated long-range hydrogen bonding between
      hydroxyl groups and the carbonyl peptide backbone can modify the properties of N
      terminal prolyl cis/trans isomerization in peptides.

PMID- 22148720
TI  - Enzyme reactions in nanoporous, picoliter volume containers.
AB  - Advancements in nanoscale fabrication allow creation of small-volume reaction
      containers that can facilitate the screening and characterization of enzymes. A
      porous, ~19 pL volume vessel has been used in this work to carry out enzyme
      reactions under varying substrate concentrations. Assessment of small-molecule
      and green fluorescent protein diffusion from the vessels indicates that pore
      sizes on the order of 10 nm can be obtained, allowing capture of proteins and
      diffusive exchange of small molecules. Glucose oxidase and horseradish peroxidase
      can be contained in these structures and diffusively fed with a solution
      containing glucose and the fluorogenic substrate amplex red through the
      engineered nanoscale pore structure. Fluorescent microscopy was used to monitor
      the reaction, which was carried out under microfluidic control. Kinetic
      characteristics of the enzyme (K(m) and V(max)) were evaluated and compared with
      results from conventional scale reactions. These picoliter, nanoporous containers
      can facilitate quick determination of enzyme kinetics in microfluidic systems
      without the requirement of surface tethering and can be used for applications in
      drug discovery, clinical diagnostics, and high-throughput screening.

PMID- 22148721
TI  - Enzymatic activity and flavor compound production in fermented silver carp fish
      paste inoculated with douchi starter culture.
AB  - Silver carp fish pastes inoculated with or without a douchi starter culture
      containing live  Aspergillus oryzae  were fermented for 30 days to produce two
      different fermented products, designated CulF and ConF, respectively. Protein
      degradation and flavor compound production during the course of fermentation were
      monitored. Proteolytic activity, generally higher in CulF than in ConF (P < 0.05)
      and dominated by acidic and serine proteases, declined to an overall minimum
      after 30 days. Myosin in the CulF and ConF extractives was completely degraded
      after 1 and 5 days, respectively. The content of free amino acids and low
      molecular weight (<1.3 kDa) peptides rose rapidly in CulF and progressively in
      ConF (P < 0.05). Ethanol, silanediol, pyrazine, phenol, and formic acid were
      prevalent volatile compounds in CulF, whereas butanol, butanoic acid, and acetic
      acid were abundant in ConF. Therefore, douchi-inoculated fermentation is an
      attractive process to produce savory fish pastes.

PMID- 22148723
TI  - Engineering transaldolase in Pichia stipitis to improve bioethanol production.
AB  - In our effort to improve the efficiency and yield of xylose-to-ethanol
      bioconversion in Pichia stipitis, the transaldolase (TAL) in the pentose
      phosphate pathway was identified as a rate-limiting enzyme for improvement. A
      mutant containing the Q263R change was first obtained by directed evolution with
      5-fold increase of activity, which was then incorporated into P. stipitesvia the
      pYDS vector to produce a genetically stable strain for fermentation on xylose. In
      comparison with the parental strain, TAL-Q263R(+) increases ethanol prodcution by
      36% and 100% as measured by volumetric production rate and specific production
      rate, respectively. Thus improving the transaldolase activity in P. stipitis can
      significantly increase the rate and yield of xylose conversion to ethanol.

PMID- 22148724
TI  - Exploring the magnetic behavior of nickel-coordinated pyrogallol[4]arene
      nanocapsules.
AB  - The magnetic behavior of nickel-seamed C-propylpyrogallol[4]arene dimeric and
      hexameric nanocapsular assemblies has been investigated in the solid state using
      a SQUID magnetometer. These dimeric and hexameric capsular entities show magnetic
      differentiation both in terms of moment per nanocapsule and potential
      antiferromagnetic interactions within individual nanocapsules. The weak
      antiferromagnetic behavior observed at low temperatures indicates dipolar
      interactions between neighboring nickel atoms; however, this effect is higher in
      the hexameric nickel-seamed assembly. The differences in magnetic behavior of
      dimer versus hexamer can be attributed to different coordination environments and
      metal arrangements in the two nanocapsular assemblies.

PMID- 22148728
TI  - Metal-macrocycle framework (MMF): supramolecular nano-channel surfaces with shape
      sorting capability.
AB  - Hollow nanostructures for the functional assembly of chemical groups with inner
      surface geometry and regulable stoichiometry enable steric design of interior
      reaction centers. Herein we report a metal-macrocycle framework (MMF) that forms
      single-crystalline nanochannels with five distinct enantiomeric pairs of guest
      binding pockets. During crystal-soaking experiments, the MMF crystals can
      encapsulate aromatic molecules with high site selectivity. First, constitutional
      isomers of dibromobenzene are captured and sorted into different binding pockets.
      Second, each of the optical isomers of (1R/1S)-1-(3-chlorophenyl)ethanol is
      included diastereoselectively into one of an enantiomeric pair of binding
      pockets. An advantage of this strategy is that the interior walls can be
      "repainted" via replacement of the trapped molecules with alternatives. Such
      guest uptake behaviors would allow highly regioselective or stereoselective
      reactions within the nanochannel.

PMID- 22148725
TI  - Structural and photophysical properties of visible- and near-IR-emitting tris
      lanthanide(III) complexes formed with the enantiomers of N,N'-bis(1-phenylethyl)
      2,6-pyridinedicarboxamide.
AB  - The enantiomers of N,N'-bis(1-phenylethyl)-2,6-pyridinedicarboxamide (L), namely,
      (R,R)-1, and (S,S)-1, react with Ln(III) ions to give stable [LnL(3)](3+)
      complexes in an anhydrous acetonitrile solution and in the solid state, as
      evidenced by electrospray ionization mass spectrometry, NMR, luminescence
      titrations, and their X-ray crystal structures, respectively. All [LnL(3)](3+)
      complexes [Ln(III) = Eu, Gd, Tb, and Yb; L = (R,R)-1 and (S,S)-1] are
      isostructural and crystallize in the cubic space group I23. Although the small
      quantum yields of the Ln(III)-centered luminescence clearly point to the poor
      efficiency of the luminescence sensitization by the ligand and the intersystem
      crossing and ligand-to-metal energy transfers, the ligand triplet-excited-state
      energy seems relatively well suited to sensitize many Ln(III) ion's emission for
      instance, in the visible (Eu and Tb), near-IR (Nd and Yb), or both regions (Pr,
      Sm, Dy, Er, and Tm).

PMID- 22148730
TI  - Selective CO2 adsorption in a robust and water-stable porous coordination polymer
      with new network topology.
AB  - A robust and water-stable porous coordination polymer [Cd(NDC)(0.5)(PCA)].G(x)
      (1) (H(2)NDC = 2,6-napthalenedicarboxylic acid, HPCA = 4-pyridinecarboxylic acid,
      G = guest molecules) with new network topology has been synthesized
      solvothermally. The framework is 3D porous material and forms a 1D channel along
      the c-axis, with the channel dimensions ~9.48 * 7.83 A(2). The compound has high
      selectivity in uptake of CO(2) over other gases (H(2), O(2), Ar, N(2), and
      CH(4)). The framework is highly stable in presence of water vapor even at 60 
      degrees C. The high CO(2) selectivity over other gases and water stability makes
      the compound promising candidate for industrial postcombustion gas separation
      application.

PMID- 22148729
TI  - Effects of pH on proteins: predictions for ensemble and single-molecule pulling
      experiments.
AB  - Protein conformations change among distinct thermodynamic states as solution
      conditions (temperature, denaturants, pH) are altered or when they are subjected
      to mechanical forces. A quantitative description of the changes in the relative
      stabilities of the various thermodynamic states is needed to interpret and
      predict experimental outcomes. We provide a framework based on the Molecular
      Transfer Model (MTM) to account for pH effects on the properties of globular
      proteins. The MTM utilizes the partition function of a protein calculated from
      molecular simulations at one set of solution conditions to predict protein
      properties at another set of solution conditions. To take pH effects into
      account, we utilized experimentally measured pK(a) values in the native and
      unfolded states to calculate the free energy of transferring a protein from a
      reference pH to the pH of interest. We validate our approach by demonstrating
      that the native-state stability as a function of pH is accurately predicted for
      chymotrypsin inhibitor 2 (CI2) and protein G. We use the MTM to predict the
      response of CI2 and protein G subjected to a constant force (f) and varying pH.
      The phase diagrams of CI2 and protein G as a function of f and pH are
      dramatically different and reflect the underlying pH-dependent stability changes
      in the absence of force. The calculated equilibrium free energy profiles as
      functions of the end-to-end distance of the two proteins show that, at various pH
      values, CI2 unfolds via an intermediate when subjected to f. The locations of the
      two transition states move toward the more unstable state as f is changed, which
      is in accord with the Hammond-Leffler postulate. In sharp contrast, force-induced
      unfolding of protein G occurs in a single step. Remarkably, the location of the
      transition state with respect to the folded state is independent of f, which
      suggests that protein G is mechanically brittle. The MTM provides a natural
      framework for predicting the outcomes of ensemble and single-molecule experiments
      for a wide range of solution conditions.

PMID- 22148731
TI  - Femtosecond photodynamics of the red/green cyanobacteriochrome NpR6012g4 from
      Nostoc punctiforme. 2. reverse dynamics.
AB  - Phytochromes are red/far-red photosensory proteins that utilize
      photoisomerization of a linear tetrapyrrole (bilin) chromophore to photoconvert
      reversibly between red- and far-red-absorbing forms (P(r) and P(fr),
      respectively). Cyanobacteriochromes (CBCRs) are related photosensory proteins
      with more diverse spectral sensitivity. The mechanisms that underlie this
      spectral diversity have not yet been fully elucidated. One of the main CBCR
      subfamilies photoconverts between a red-absorbing 15Z ground state, like the
      familiar P(r) state of phytochromes, and a green-absorbing photoproduct
      ((15E)P(g)). We have previously used the red/green CBCR NpR6012g4 from the
      cyanobacterium Nostoc punctiforme to examine ultrafast photodynamics of the
      forward photoreaction. Here, we examine the reverse reaction. Using excitation
      interleaved transient absorption spectroscopy with broadband detection and
      multicomponent global analysis, we observed multiphasic excited-state dynamics.
      Interleaved excitation allowed us to identify wavelength-dependent shifts in the
      ground-state bleach that equilibrated on a 200 ps time scale, indicating ground
      state heterogeneity. Compared to the previously studied forward reaction, the
      reverse reaction has much faster excited-state decay time constants and
      significantly higher photoproduct yield. This work thus demonstrates striking
      differences between the forward and reverse reactions of NpR6012g4 and provides
      clear evidence of ground-state heterogeneity in the phytochrome superfamily.

PMID- 22148732
TI  - Selective protein separation using siliceous materials with a trimethoxysilane
      containing glycopolymer.
AB  - A copolymer with alpha-D-mannose (Man) and trimethoxysilane (TMS) units was
      synthesized for immobilization on siliceous matrices such as a sensor cell and
      membrane. Immobilization of the trimethoxysilane-containing copolymer on the
      matrices was readily performed by incubation at high heat. The recognition of
      lectin by poly(Man-r-TMS) was evaluated by measurement with a quartz crystal
      microbalance (QCM) and adsorption on an affinity membrane, QCM results showed
      that the mannose-binding protein, concanavalin A, was specifically bound on a
      poly(Man-r-TMS)-immobilized cell with a higher binding constant than bovine serum
      albumin. The amount of concanavalin A adsorbed during permeation through a
      poly(Man-r-TMS)-immobilized membrane was higher than that through an unmodified
      membrane. Moreover, the concanavalin A adsorbed onto the poly(Man-r-TMS)
      immobilized membrane was recoverable by permeation of a mannose derivative at
      high concentration.

PMID- 22148733
TI  - Nanoparticles in measurement science.

PMID- 22148734
TI  - Orientation of alpha-sexithiophene on friction-transferred polythiophene film.
AB  - Controlling the molecular orientation of the conjugated oligomer, alpha
      sexithiophene (6T), is crucial to improve organic optoelectronic device
      performance. Most 6T molecules evaporated onto quartz and SiO(2)/Si substrates
      orient nearly perpendicular to the substrate. Here, we report the formation of
      oriented thin films of 6T on in-plane-oriented polythiophene (PT) films formed by
      the friction-transfer method. 6T was evaporated onto oriented PT films under
      vacuum. The films were investigated by polarized optical microscopy, polarized
      ultraviolet-visible light (UV-vis) absorption spectroscopy, and grazing incidence
      X-ray diffraction measurement (GIXD). In all spectra, larger absorbance derived
      from PT and 6T was observed, in parallel polarization to the friction direction,
      compared to that of orthogonal polarization. These results indicate that the 6T
      molecular axis is aligned in the friction direction (PT chain direction) of PT
      films. GIXD also confirmed that the 6T molecular axis was aligned parallel to the
      PT chain axis. In contrast, 6T molecules evaporated onto quartz and
      poly(ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-coated silicon
      substrates aligned nearly perpendicular to the substrate. These results indicate
      that oriented PT films induce 6T orientation parallel to the PT chain direction.

PMID- 22148735
TI  - BbgIV Is an Important Bifidobacterium beta-Galactosidase for the Synthesis of
      Prebiotic Galactooligosaccharides at High Temperatures.
AB  - The individual contributions of four beta-galactosidases present in
      Bifidobacterium bifidum NCIMB 41171 toward galactooligosaccharide (GOS) synthesis
      were investigated. Although the beta-galactosidase activity of the whole cells
      significantly decreased as a function of temperature (40-75  degrees C), GOS
      yield was at its maximum at 65  degrees C. Native-PAGE of the whole cells showed
      that the contributions of BbgIII and BbgIV to GOS synthesis increased as the
      temperature increased. Moreover, BbgIII and BbgIV were found to be more
      temperature stable and to produce a higher GOS yield than BbgI and BbgII, when
      used in their free form. The GOS yield using BbgIV was 54.8% (percent of total
      carbohydrates) and 63.9% (percent lactose converted to GOS) at 65  degrees C from
      43% w/w lactose. It was shown that BbgIV is the most important beta-galactosidase
      in B. bifidum NCIMB 41171 and can be used for GOS synthesis at elevated
      temperatures. 

PMID- 22148737
TI  - Determining the absolute configuration of two marine compounds using vibrational
      chiroptical spectroscopy.
AB  - Chiroptical techniques are increasingly employed for assigning the absolute
      configuration of chiral molecules through comparison of experimental spectra with
      theoretical predictions. For assignment of natural products, electronic
      chiroptical spectroscopies such as electronic circular dichroism (ECD) are
      routinely applied. However, the sensitivity of electronic spectral parameters to
      experimental conditions and the theoretical methods employed can lead to
      incorrect assignments. Vibrational chiroptical methods (vibrational circular
      dichroism, VCD, and Raman optical activity, ROA) provide more reliable
      assignments, although they, in particular ROA, have been little explored for
      assignments of natural products. In this study, the ECD, VCD, and ROA chiroptical
      spectroscopies are evaluated for the assignment of the absolute configuration of
      a highly flexible natural compound with two stereocenters and an asymmetrically
      substituted double bond, the marine antibiotic Synoxazolidinone A (SynOxA),
      recently isolated from the sub-Arctic ascidian Synoicum pulmonaria.
      Conformationally averaged nuclear magnetic resonance (NMR), ECD, Raman, ROA,
      infrared (IR) and VCD spectral parameters are computed for the eight possible
      stereoisomers of SynOxA and compared to experimental results. In contrast to
      previously reported results, the stereochemical assignment of SynOxA based on ECD
      spectral bands is found to be unreliable. On the other hand, ROA spectra allow
      for a reliable determination of the configuration at the double bond and the ring
      stereocenter. However, ROA is not able to resolve the chlorine-substituted
      stereogenic center on the guanidinium side chain of SynOxA. Application of the
      third chiroptical method, VCD, indicates unique spectral features for all eight
      SynOxA isomers in the theoretical spectra. Although the experimental VCD is weak
      and restricted by the limited amount of  sample, it allows for a tentative
      assignment of the elusive chlorine-substituted stereocenter. VCD chiroptical
      analysis of a SynOxA derivative with three stereocenters, SynOxC, results in the
      same absolute configuration as for SynOxA. Despite the experimental challenges,
      the results convincingly prove that the assignment of absolute configuration
      based on vibrational chiroptical methods is more reliable than for ECD.

PMID- 22148738
TI  - Ultrasmall near-infrared Ag2Se quantum dots with tunable fluorescence for in vivo
      imaging.
AB  - A strategy is presented that involes coupling Na(2)SeO(3) reduction with the
      binding of silver ions and alanine in a quasi-biosystem to obtain ultrasmall,
      near-infrared Ag(2)Se quantum dots (QDs) with tunable fluorescence at 90  degrees
      C in aqueous solution. This strategy avoids high temperatures, high pressures,
      and organic solvents so that water-dispersible sub-3 nm Ag(2)Se QDs can be
      directly obtained. The photoluminescence of the Ag(2)Se QDs was size-dependent
      over a wavelength range from 700 to 820 nm, corresponding to sizes from 1.5 +/-
      0.4 to 2.4 +/- 0.5 nm, with good monodispersity. The Ag(2)Se QDs are less
      cytotoxic than other nanomaterials used for similar applications. Furthermore,
      the NIR fluorescence of the Ag(2)Se QDs could penetrate through the abdominal
      cavity of a living nude mouse and could be detected on its back side,
      demonstrating the potential applications of these less toxic NIR Ag(2)Se QDs in
      bioimaging.

PMID- 22148743
TI  - Electrical conductivity and luminescence in coordination polymers based on
      copper(I)-halides and sulfur-pyrimidine ligands.
AB  - The solvothermal reactions between pyrimidinedisulfide (pym(2)S(2)) and CuI or
      CuBr(2) in CH(2)Cl(2):CH(3)CN lead to the formation of [Cu(11)I(7)(pymS)(4)](n)
      (pymSH = pyrimidine-2(1H)-thione) (1) and the dimer [Cu(II)(MU-Br)(Br)L](2) (L =
      2-(pyrimidin-2-ylamino)-1,3-thiazole-4-carbaldehyde) (2). In the later reaction,
      there is an in situ S-S, S-C(sp(2)), and C(sp(2))-N multiple bond cleavage of the
      pyrimidinedisulfide resulting in the formation of 2-(pyrimidin-2-ylamino)-1,3
      thiazole-4-carbaldehyde. Interestingly, similar reactions carried out just with a
      change in the solvent (H(2)O:CH(3)CN instead of CH(2)Cl(2):CH(3)CN) give rise to
      the formation of coordination polymers with rather different architectures. Thus,
      the reaction between pym(2)S(2) and CuI leads to the formation of
      [Cu(3)I(pymS)(2)](n) (3) and [CuI(pym(2)S(3))] (pym(2)S(3) = pyrimidiltrisulfide)
      (4), while [Cu(3)Br(pymS)(2)](n) (5) is isolated in the reaction with CuBr(2).
      Finally, the solvothermal reactions between CuI and pyrimidine-2-thione (pymSH)
      in CH(2)Cl(2):CH(3)CN at different ratios, 1:1 or 2:1, give the polymers
      [Cu(2)I(2)(pymSH)(2)](n) (6) and [Cu(2)I(2)(pymSH)](n) (7), respectively. The
      structure of the new compounds has been determined by X-ray diffraction. The
      studies of the physical properties of the novel coordination polymers reveal that
      compounds 3 and 5 present excellent electrical conductivity values at room
      temperature, while compounds 1, 3, and 5-7 show luminescent strong red emission
      at room temperature.

PMID- 22148739
TI  - Isolation of alpaca anti-hapten heavy chain single domain antibodies for
      development of sensitive immunoassay.
AB  - Some unique subclasses of Camelidae antibodies are devoid of the light chain, and
      the antigen binding site is comprised exclusively of the variable domain of the
      heavy chain (VHH). Although conventional antibodies dominate current assay
      development, recombinant VHHs have a high potential as alternative reagents for
      the next generation of immunoassay. We expressed VHHs from an immunized alpaca
      and developed a VHH-based immunoassay using 3-phenoxybenzoic acid (3-PBA), a
      major metabolite of pyrethroid insecticides as a model system. A phage VHH
      library was constructed, and seven VHH clones were selected by competitive
      binding with 3-PBA. The best immunoassay developed with one of these VHHs showed
      an IC(50) of 1.4 ng/mL (limit of detection (LOD) = 0.1 ng/mL). These parameters
      were further improved by using the phage borne VHH, IC(50) = 0.1 ng/mL and LOD =
      0.01 ng/mL. Both assays showed a similar tolerance to methanol and
      dimethylsulfoxide up to 50% in assay buffer. The assay was highly specific to 3
      PBA and its 4-hydroxylated derivative, 4-hydroxy 3-PBA, (150% cross reactivity)
      with negligible cross reactivity with other tested structural analogues, and the
      recovery from spiked urine sample ranged from 80 to 112%. In conclusion, a highly
      specific and sensitive VHH for 3-PBA was developed using sequences from immunized
      alpaca and phage display technology for antibody selection.

PMID- 22148740
TI  - Novel modifications in RNA.
AB  - The past several years have seen numerous reports of new chemical modifications
      for use in RNA. In addition, in that time period, we have seen the discovery of
      several previously unknown naturally occurring modifications that impart novel
      properties on the parent RNAs. In this review, we describe recent discoveries in
      these areas with a focus on RNA modifications that introduce spectroscopic tags,
      reactive handles, or new recognition properties.

PMID- 22148745
TI  - Transition-metal-centered nine-membered boron rings: McB9 and McB9(-) (M = Rh,
      Ir).
AB  - We report the observation of two transition-metal-centered nine-atom boron rings,
      RhcB(9)(-) and IrcB(9)(-). These two doped-boron clusters are produced in a laser
      vaporization supersonic molecular beam and characterized by photoelectron
      spectroscopy and ab initio calculations. Large HOMO-LUMO gaps are observed in the
      anion photoelectron spectra, suggesting that neutral RhcB(9) and IrcB(9) are
      highly stable, closed shell species. Theoretical calculations show that RhcB(9)
      and IrcB(9) are of D(9h) symmetry. Chemical bonding analyses reveal that these
      complexes are doubly aromatic, each with six completely delocalized pi and sigma
      electrons, which describe the bonding between the central metal atom and the
      boron ring. This work establishes firmly the metal-doped B rings as a new class
      of novel aromatic molecular wheels.

PMID- 22148744
TI  - Catalytic conversion of graphene into carbon nanotubes via gold nanoclusters at
      low temperatures.
AB  - Here, we present the catalytic conversion of graphene layers into carbon
      nanotubes (CNTs), in the presence of Au nanoparticles (AuNPs) without the need
      for an additional carbon source. We have demonstrated that this catalytic process
      takes place at temperatures as low as 500  degrees C. No other oxide supports
      decorated with AuNPs were found to grow CNTs at this temperature. These findings
      highlight the high activity of graphene when used as a support for catalytic
      reactions.

PMID- 22148746
TI  - Sampling the proton transfer reaction coordinate in mixed quantum-classical
      molecular dynamics simulations.
AB  - An umbrella sampling approach based on the vibrational energy gap is presented
      and examined for exploring the reaction coordinate for a proton transfer (PT)
      reaction. The technique exploits the fact that for a PT reaction the energy gap
      between the vibrational ground and excited states of the transferring proton
      reaches a minimum at the transition state. Umbrella sampling is used within mixed
      quantum-classical simulations to identify the transition state configurations and
      explore the reaction free energy curve and vibrationally nonadiabatic coupling.
      The method is illustrated by application to a model phenol-amine proton transfer
      reaction complex in a nanoconfined solvent. The results from this new umbrella
      sampling approach are consistent with those obtained from previous umbrella
      sampling calculations based on a collective solvent coordinate. This sampling
      approach further provides insight into the vibrationally nonadiabatic coupling
      for the proton transfer reaction and has potential for simulating vibrational
      spectra of PT reaction complexes in solution.

PMID- 22148747
TI  - Awakening of a ferrous complex's electronic spin in an aqueous solution induced
      by a chemical stimulus.
AB  - A low-spin, macrocyclic iron(II) complex in an aqueous solution responds to the
      addition of a chemical reactant (dithionite) by transformation into a high-spin
      complex, detectable by measurement of the longitudinal relaxation time (T(1)) of
      surrounding water hydrogen nuclear spins. The initial compound does not modify
      T(1) of pure water at concentrations as high as 4 mM. The response is pH
      dependent, and the complex is robust at a variety of conditions.

PMID- 22148749
TI  - Systematic study on the effect of solvent removal rate on the morphology of
      solvent vapor annealed ABA triblock copolymer thin films.
AB  - Nanoscale self-assembly of block copolymer thin films has garnered significant
      research interest for nanotemplate design and membrane applications. To fulfill
      these roles, control of thin film morphology and orientation is critical. Solvent
      vapor annealing (SVA) treatments can be used to kinetically trap morphologies in
      thin films not achievable by traditional thermal treatments, but many variables
      affect the outcome of SVA, including solvent choice, total solvent
      concentration/swollen film thickness, and solvent removal rate. In this work, we
      systematically examined the effect of solvent removal rate on the final thin film
      morphology of a cylinder-forming ABA triblock copolymer. By kinetically trapping
      the film morphologies at key points during the solvent removal process and then
      using successive ultraviolet ozone (UVO) etching steps followed by atomic force
      microscopy (AFM) imaging to examine the through-film morphologies of the films,
      we determined that the mechanism for cylinder reorientation from substrate
      parallel to substrate-perpendicular involved the propagation of changes at the
      free surface through the film toward the substrate as a front. The degree of
      reorientation increased with successively slower solvent removal rates.
      Furthermore, the AFM/UVO etching scheme permitted facile real-space analysis of
      the thin film internal structure in comparison to cross-sectional transmission
      electron microscopy.

PMID- 22148751
TI  - Phase transitions in prequenched mesomorphic isotactic polypropylene during
      heating and annealing processes as revealed by simultaneous synchrotron SAXS and
      WAXD technique.
AB  - Time-resolved simultaneous synchrotron small-angle X-ray scattering (SAXS) and
      wide-angle X-ray diffraction (WAXD) technique was used to investigate the phase
      transitions in prequenched mesomorphic isotactic polypropylene (iPP) samples
      during heating and annealing processes, respectively. For the heating process, it
      is shown that the mesomorphic-to-monoclinic phase transition is relatively faster
      for the mesomorphic iPP sample obtained with the high quenching rate than that
      with the low quenching rate. For the former, the stability of alpha-monoclinic
      crystals formed during heating is relatively higher. As for the annealing
      process, WAXD and SAXS data illustrate that the higher the annealing temperature
      (T(a)), the earlier the mesomorphic-to-monoclinic phase transition occurs.
      Namely, T(a) controls the phase transition rate. Both heating and annealing
      processes show that the increase of content of alpha-monoclinic crystal phase is
      mainly at the expense of the mesomorphic phase, with the content of amorphous
      phase almost invariable. The isothermal crystallization kinetics for the
      prequenched mesomorphic iPP sample was analyzed through the Avrami equation,
      revealing a two-dimensional crystal growth under the diffusion-limited mechanism.

PMID- 22148750
TI  - Post-translational modification of Cu/Zn superoxide dismutase under anaerobic
      conditions.
AB  - In eukaryotic organisms, the largely cytosolic copper- and zinc-containing
      superoxide dismutase (Cu/Zn SOD) enzyme represents a key defense against reactive
      oxygen toxicity. Although much is known about the biology of this enzyme under
      aerobic conditions, less is understood regarding the effects of low oxygen levels
      on Cu/Zn SOD enzymes from diverse organisms. We show here that like bakers' yeast
      (Saccharomyces cerevisiae), adaptation of the multicellular Caenorhabditis
      elegans to growth at low oxygen levels involves strong downregulation of its
      Cu/Zn SOD. Much of this regulation occurs at the post-translational level where
      CCS-independent activation of Cu/Zn SOD is inhibited. Hypoxia inactivates the
      endogenous Cu/Zn SOD of C. elegans Cu/Zn SOD as well as a P144 mutant of S.
      cerevisiae Cu/Zn SOD (herein denoted Sod1p) that is independent of CCS. In our
      studies of S. cerevisiae Sod1p, we noted a post-translational modification to the
      inactive enzyme during hypoxia. Analysis of this modification by mass
      spectrometry revealed phosphorylation at serine 38. Serine 38 represents a
      putative proline-directed kinase target site located on a solvent-exposed loop
      that is positioned at one end of the Sod1p beta-barrel, a region immediately
      adjacent to residues previously shown to influence CCS-dependent activation.
      Although phosphorylation of serine 38 is minimal when the Sod1p is abundantly
      active (e.g., high oxygen level), up to 50% of Sod1p can be phosphorylated when
      CCS activation of the enzyme is blocked, e.g., by hypoxia or low-copper
      conditions. Serine 38 phosphorylation can be a marker for inactive pools of
      Sod1p.

PMID- 22148752
TI  - Apple peels, from seven cultivars, have lipase-inhibitory activity and contain
      numerous ursenoic acids as identified by LC-ESI-QTOF-HRMS.
AB  - Apple peel contains numerous phytochemicals, many of which show bioactivity. This
      study investigated the identity of triterpenoid compounds contained in ethanolic
      extracts of peel from seven apple cultivars. Using HPLC-ESI-QTOF-HRMS, accurate
      mass information was obtained for 43 compounds, and chemical identity was
      inferred from the calculated elemental composition, fragment masses, ms/ms, and a
      limited set of authentic standards. Compounds were identified as triterpene acids
      and tentatively identified as ursenoic (or oleanoic) acid derivatives containing
      hydroxyl, oxo, and coumaroyloxy groups. These apple skin extracts exhibited
      lipase-inhibitory activity, which may be linked to the ursenoic acid content.
      Furthermore, both triterpene content and lipase-inhibitory activity varied by
      cultivar.

PMID- 22148748
TI  - Allosteric modulation of seven transmembrane spanning receptors: theory,
      practice, and opportunities for central nervous system drug discovery.

PMID- 22148754
TI  - Discovery of a novel class of orally active trypanocidal N-myristoyltransferase
      inhibitors.
AB  - N-Myristoyltransferase (NMT) represents a promising drug target for human African
      trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma
      brucei. We report the optimization of a high throughput screening hit (1) to give
      a lead molecule DDD85646 (63), which has potent activity against the enzyme
      (IC(50) = 2 nM) and T. brucei (EC(50) = 2 nM) in culture. The compound has good
      oral pharmacokinetics and cures rodent models of peripheral HAT infection. This
      compound provides an excellent tool for validation of T. brucei NMT as a drug
      target for HAT as well as a valuable lead for further optimization.

PMID- 22148757
TI  - Divalent-metal-stabilized aluminophosphates exhibiting a new zeolite framework
      topology.
AB  - Two divalent-metal-containing aluminophosphates,
      (C(5)H(14)N(2))[Co(2)Al(4)P(6)O(24)] and (C(5)H(14)N(2))[Zn(2)Al(4)P(6)O(24)]
      (denoted as MAPO-CJ62; M = Co, Zn), have been hydrothermally synthesized by using
      N-methylpiperazine as the structure directing agent. Their structures are
      determined by single crystal X-ray diffraction and further characterized by
      powder X-ray diffraction, inductively coupled plasma, and thermogravimetric and
      diffuse reflectance spectroscopy analyses. Both of these two compounds exhibit a
      new zeolite framework topology. This new zeolite framework contains 1-dimensional
      8-ring channels running along the [010] direction. All the metal and P atoms are
      tetrahedrally coordinated and alternately connected to each other through
      bridging O atoms. Inductively coupled plasma analysis shows that the molar ratio
      of M:Al in MAPO-CJ62 is 1:2. The M(2+) ions in MAPO-CJ62 selectively occupy two
      of the three possible crystallographically distinct positions. A pure
      aluminophosphate analogue of MAPO-CJ62 without M(2+)-incorporation, denoted as
      AlPO-CJ62, has not been obtained in our experiment so far. The necessity of
      introducing M(2+) ions and their ordered distribution in MAPO-CJ62 has been
      elucidated by analyzing the distortions of Al-centered tetrahedra in the
      hypothetical framework of AlPO-CJ62.

PMID- 22148755
TI  - Targeting diverse signaling interaction sites allows the rapid generation of
      bivalent kinase inhibitors.
AB  - The identification of potent and selective modulators of protein kinase function
      remains a challenge, and new strategies are needed for generating these useful
      ligands. Here, we describe the generation of bivalent inhibitors of three
      unrelated protein kinases: the CAMK family kinase Pim1, the mitogen-activated
      protein kinase (MAPK) p38alpha, and the receptor tyrosine kinase (RTK) epidermal
      growth factor receptor (EGFR). These bivalent inhibitors consist of an ATP
      competitive inhibitor that is covalently tethered to an engineered form of the
      self-labeling protein O(6)-alkylguanine-DNA alkyltransferase (SNAP-tag). In each
      example, SNAP-tag is fused to a peptide ligand that binds to a signaling
      interaction site of the kinase being targeted. These interactions increase the
      overall selectivity and potency of the bivalent inhibitors that were generated.
      The ability to exploit disparate binding sites in diverse kinases points to the
      generality of the method described. Finally, we demonstrate that ATP-competitive
      inhibitors that are conjugated to the bio-orthogonal tag O(4)-benzyl-2-chloro-6
      aminopyrimidine (CLP) are cell-permeable. The selective labeling of SNAP-tag with
      CLP conjugates allows the rapid assembly of bivalent inhibitors in living cells.

PMID- 22148759
TI  - Robust data processing and normalization strategy for MALDI mass spectrometric
      imaging.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging
      (MSI) provides localized information about the molecular content of a tissue
      sample. To derive reliable conclusions from MSI data, it is necessary to
      implement appropriate processing steps in order to compare peak intensities
      across the different pixels comprising the image. Here, we review commonly used
      normalization methods, and propose a rational data processing strategy, for
      robust evaluation and modeling of MSI data. The approach includes newly developed
      heuristic methods for selecting biologically relevant peaks and pixels to reduce
      the size of a data set and remove the influence of the applied MALDI matrix. The
      methods are demonstrated on a MALDI MSI data set of a sagittal section of rat
      brain (4750 bins, m/z = 50-1000, 111 * 185 pixels) and the proposed preferred
      normalization method uses the median intensity of selected peaks, which were
      determined to be independent of the MALDI matrix. This was found to effectively
      compensate for a range of known limitations associated with the MALDI process and
      irregularities in MS image sampling routines. This new approach is relevant for
      processing of all MALDI MSI data sets, and thus likely to have impact in
      biomarker profiling, preclinical drug distribution studies, and studies
      addressing underlying molecular mechanisms of tissue pathology.

PMID- 22148758
TI  - Multiplexed cancer biomarker detection using quartz-based photonic crystal
      surfaces.
AB  - A photonic crystal (PC) surface is demonstrated as a high-sensitivity platform
      for detection of a panel of 21 cancer biomarker antigens using a sandwich enzyme
      linked immunosorbent assay (ELISA) microarray format. A quartz-based PC structure
      fabricated by nanoimprint lithography, selected for its low autofluorescence,
      supports two independent optical resonances that simultaneously enable
      enhancement of fluorescence detection of biomarkers and label-free quantification
      of the density of antibody capture spots. A detection instrument is demonstrated
      that supports fluorescence and label-free imaging modalities, with the ability to
      optimize the fluorescence enhancement factor on a pixel-by-pixel basis throughout
      the microarray using an angle-scanning approach for the excitation laser that
      automatically compensates for variability in surface chemistry density and
      capture spot density. Measurements show that the angle-scanning illumination
      approach reduces the coefficient of variation of replicate assays by 20-99%
      compared to ordinary fluorescence microscopy, thus supporting reduction in limits
      of detectable biomarker concentration. Using the PC resonance, biomarkers in
      mixed samples were detectable at the lowest concentrations tested (2.1-41 pg/mL),
      resulting in a three-log range of quantitative detection.

PMID- 22148760
TI  - Hydration numbers of nonelectrolytes from acoustic methods.

PMID- 22148761
TI  - Carbon acidities of aromatic compounds.  2.  Ionic probes of aromaticity in
      annelated rings.

PMID- 22148762
TI  - Circular dichroism of oxiranes:  an independent systems/perturbation approach.

PMID- 22148763
TI  - The 5-hydroxy-1,2,3-oxadiazolinium ion:  neighboring group interaction between N
      nitroso and aldehyde carbonyl.

PMID- 22148764
TI  - An EXAFS study of cobalt-manganese/silica bimetallic solvated metal atom
      dispersed (SMAD) catalysts.

PMID- 22148765
TI  - Comparative molecular field analysis (CoMFA).  1.  Effect of shape on binding of
      steroids to carrier proteins.

PMID- 22148766
TI  - Infrared, resonance Raman, and excitation profile studies of Os2(O2CCH3)4Cl2 and
      Os2(O2CCD3)4Cl2.  The assignment of the osmium-osmium stretching vibration for a
      complex involving an osmium-osmium multiple bond.

PMID- 22148767
TI  - A symmetry-based procedure for the determination of molecular geometry changes
      following electronic excitation.  1.  Outline of the qualitative method.

PMID- 22148768
TI  - A symmetry-based procedure for the determination of molecular geometry changes
      following electronic excitation.  2.  Relaxation pathways for the excited states
      of ethylene, acetone, butadiene, and methylenimine.

PMID- 22148769
TI  - Excess free energy of liquids from molecular dynamics simulations.  Application
      to water models.

PMID- 22148770
TI  - Iron(I)-induced demethanation of tert-butyl-substituted nitriles in the gas
      phase.  A case of remote functionalization of carbon-carbon bonds.

PMID- 22148771
TI  - Do supra-antara paths really exist for 2 + 2 cycloaddition reactions? Analytical
      computation of the MC-SCF Hessians for transition states of ethylene with
      ethylene, singlet oxygen, and ketene.

PMID- 22148772
TI  - Pseudorotation in pentacoordinated phosphorus compounds.  The influence of the
      conformational transmission effect on the barriers to pseudorotation in cyclic
      alkoxyphosphoranes.

PMID- 22148773
TI  - A single-crystal ESR study on radicals derived from rac- and meso-1,2-dimethyl
      1,2-diphenyldiphosphine disulfide:  stereochemical selection in radical
      formation.

PMID- 22148774
TI  - Resonance Raman studies of dioxygen adducts of cobalt-substituted heme proteins
      and model compounds.  Vibrationally coupled dioxygen and the issues of multiple
      structures and distal side hydrogen bonding.

PMID- 22148775
TI  - Crystal structure, CP/MAS xeon-129 and carbon-13 NMR of local ordering in
      Dianin's compound clathrates.

PMID- 22148776
TI  - Separation by sodium-23 NMR of the unimolecular and bimolecular components of the
      dissociation kinetics of 18-crown-6-Na+ in some nonaqueous solvents.

PMID- 22148777
TI  - Is bound carbonyl linear or bent in heme proteins?  Evidence from resonance Raman
      and infrared spectroscopic data.

PMID- 22148778
TI  - The reaction of n-butyllithium with diphenylacetylene:  structure elucidation of
      the mono- and dilithio product by one- and two-dimensional NMR spectroscopy, x
      ray analysis, and MNDO calculations.  Agostic activation by lithium.

PMID- 22148779
TI  - Zigzag collapse of four-membered rings generated by additions of halonium ions to
      cyclopropanes.

PMID- 22148780
TI  - Superacid solutions in hydrogen fluoride.

PMID- 22148781
TI  - Structures of lithium salts of 2,3,3-trimethylindolenine and its 5-methoxy
      derivative in solution and the solid state.

PMID- 22148782
TI  - Thermodynamic studies of competitive adduct formation:  single- and double
      insertion reactions of carbon monoxide with rhodium octaethylporphyrin dimer.

PMID- 22148783
TI  - Formation of bridging acylium and nitrilium complexes by reaction of carbon
      monoxide and tert-butyl isocyanide with a bridging diiron methylidyne complex. 
      Evidence for strong electron donation from the Fe2C core onto the .mu.
      CHC.tplbond.O and .mu.-CHC.tplbond.NR ligands.

PMID- 22148784
TI  - IR flash kinetic spectroscopy of transients generated by irradiation of
      cyclopentadienylcobalt dicarbonyl in the gas phase and in solution.

PMID- 22148785
TI  - Ground spin state variability in [Fe4S4(SR)4]3-.  Synthetic analogs of the
      reduced clusters in ferredoxins and other iron-sulfur proteins:  cases of extreme
      sensitivity of electronic state and structure to extrinsic factors.

PMID- 22148787
TI  - Divergent kinetic and thermodynamic acidity in organotransition-metal hydride
      complexes: synthesis, structure, and reactivity of the rhenium anion of Li+
      [(.eta.-C5H5)Re(NO)(PPh3)]-.

PMID- 22148786
TI  - Synthesis, structure, and reactions of chiral rhenium vinylidene and acetylide
      complexes of the formula [(.eta.5-C5H5)Re(NO)(PPh3)(X)]n+. Vinylidene complexes
      that are formed by stereospecific C.beta. electrophilic attack, exist as two
      Re=C=C geometric isomers, and undergo stereospecific C.alpha. nucleophilic
      attack.

PMID- 22148788
TI  - Hole delocalization in oxidized cerium(IV) porphyrin sandwich complexes.

PMID- 22148789
TI  - Mechanistic studies of alkene epoxidation catalyzed by nickel(II) cyclam
      complexes.  Oxygen-18 labeling and substituent effects.

PMID- 22148790
TI  - Preparation, electrochemical oxidation, and XPS studies of unsymmetrical
      ruthenocenes bearing the pentamethylcyclopentadienyl ligand.

PMID- 22148791
TI  - Incorporation of phenoxy groups in self-assembled monolayers of trichlorosilane
      derivatives.  Effects on film thickness, wettability, and molecular orientation.

PMID- 22148792
TI  - Eliminations from (E)-O-Arylbenzaldoximes promoted by tertiary amines in
      acetonitrile.  Effects of aryl substituents, base strength, and leaving group
      upon the nitrile-forming transition state.

PMID- 22148793
TI  - Comparison of free energy changes for nitrogen inversion and electron loss.  2. 
      8-Azabicyclo[3.2.1]octyl and 7-azabicyclo[2.2.1]heptyl systems.

PMID- 22148794
TI  - Calixarenes.  22.  Synthesis, properties, and metal complexation of
      aminocalixarenes.

PMID- 22148795
TI  - The tunichromes.  A class of reducing blood pigments from sea squirts: 
      isolation, structures, and vanadium chemistry.

PMID- 22148796
TI  - Biomimetic syntheses of pretetramides.  1.  Synthesis of pretetramide by tandem
      extension of a polyketide chain.

PMID- 22148797
TI  - Biomimetic syntheses of pretetramides.  2.  A synthetic route based on a
      preformed D ring.

PMID- 22148798
TI  - Biomimetic syntheses of pretetramides.  3.  Synthesis of 6-methylpretetramides
      using a preassembled D ring template.

PMID- 22148799
TI  - Stereocontrolled construction of an ingenol prototype having a complete array of
      oxygenated and unsaturated centers.

PMID- 22148800
TI  - Molecular recognition in aqueous media.  Conformationally restricted water
      soluble cyclophanes derived from 6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine.

PMID- 22148801
TI  - Structural and synthetic studies of the spore germination autoinhibitor,
      gloeosporone.

PMID- 22148803
TI  - Kinetic solvation pressure:  a measure of environmental effects on reaction
      rates.  1.  Application to hydrophobic systems.

PMID- 22148802
TI  - Conformational analysis of lipophilic antifolates:  crystal structure of
      piritrexim and a theoretical evaluation of its binding to dihydrofolate
      reductase.

PMID- 22148804
TI  - Thiamin diphosphate catalysis.  Mechanistic divergence as a probe of substrate
      activation of pyruvate decarboxylase.

PMID- 22148805
TI  - Effect of heme orientation on the reduction potential of cytochrome b5.

PMID- 22148806
TI  - The reaction of dimethylsilylene with carbon monoxide in low-temperature
      matrices.

PMID- 22148807
TI  - Ligand field transitions and the origin of zero field splitting in [PPh4][FeCl4]
      and [NEt4][Fe(SR)4] (R = 2,3,5,6-Me4C6H):  a model for the high-spin Fe(III) site
      in rubredoxin.

PMID- 22148808
TI  - Nonequilibrated multiple luminescence from CpRe(CO)2(4-Phpy) in 293 K solution.

PMID- 22148809
TI  - Permethylmanganates.  Synthesis and characterization of divalent [MnMe42-],
      trivalent [MnMe52-], and tetravalent [MnMe62-].

PMID- 22148810
TI  - Enantioselective ring cleavage of meso-epoxides with B
      halodiisopinocampheylboranes.

PMID- 22148812
TI  - Novel synthesis of tetrahydrofurans via a synthetic equivalent to a carbonyl
      ylide.

PMID- 22148811
TI  - Organometallic chemical vapor deposition of III/V compound semiconductors with
      novel organometallic precursors.

PMID- 22148813
TI  - Bis(.mu.-acetato)(.mu.-oxo)-bis(tris(pyridine)ruthenium(III)) ion:  a ruthenium
      analog of the hemerythrin active center.

PMID- 22148814
TI  - Boratirane:  preparation and characterization of trans-1,1,2,3
      tetraphenylboratirane.

PMID- 22148815
TI  - Acyloxyborane:  an activating device for carboxylic acids.

PMID- 22148816
TI  - Syndiospecific propylene polymerizations with Group IVB metallocenes.

PMID- 22148817
TI  - Correlation of carbon-13 and nitrogen-15 chemical shifts in selectively and
      uniformly labeled proteins by heteronuclear two-dimensional NMR spectroscopy.

PMID- 22148818
TI  - Mass measurements using isotopically labeled solvents reveal the extent of
      solvent transport during redox in thin films on electrodes.

PMID- 22148819
TI  - Facile cleavage of C-H bonds.  Reaction of trimethylaluminum with
      bis(diphenylphosphinoyl)methane.  Synthesis and molecular structure of
      [Al(CH3)][(C6H5)2P(O)CP(O)(C6H5)2]2[Al(CH3)2]2.

PMID- 22148820
TI  - The x-ray structure of flavohemoglobin.  A semisynthetic hydroxylase.

PMID- 22148821
TI  - Ring enlargement of boracyclanes via sequential one carbon homologation.  The
      first synthesis of boracyclanes in the strained medium ring range.

PMID- 22148822
TI  - Total synthesis of (.+-.)-punctaporonin B.

PMID- 22148823
TI  - The peptide way to macrocyclic bifunctional chelating agents: synthesis of 2-(p
      nitrobenzyl)-1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid and
      study of its yttrium(III) complex.

PMID- 22148824
TI  - Highly sensitive flash photolysis with optical waveguides:  photodeposition of
      silver onto particulate TiO2 from solution.

PMID- 22148825
TI  - Observation of a local minimum on the S1 surface of cis-stilbene solvated in
      inert gas clusters.

PMID- 22148826
TI  - Reaction of dimesitylsilylene in a cryogenic oxygen matrix.  IR spectroscopic
      observation of a silylene-oxygen adduct.

PMID- 22148827
TI  - Unusually lower barrier to reductive elimination in an 18-electron .eta.3
      allyl(organo)nickel(II) complex than those for the 16-electron .eta.3-allyl
      counterpart and its 16-electron .eta.1-allyl isomer.

PMID- 22148828
TI  - Optically active 2-ethenyl-1,3-dioxolanones as 3-carbon synthons.  Allylnickel
      derivatives as homoenolate equivalents.

PMID- 22148829
TI  - Directed Arbuzov-type reactions of 2-cyano-1,1-dimethylethyl deoxynucleoside
      phosphites.

PMID- 22148830
TI  - The resolution of racemic hydroperoxides:  the preparation of optically pure
      hydroperoxide natural products.

PMID- 22148832
TI  - Computer software reviews.

PMID- 22148831
TI  - Principal component self-modeling analysis applied to conformational
      equilibration of 1,3-butadiene vapor.  UV spectra and thermodynamic parameters of
      the two conformers.

PMID- 22148834
TI  - Recognition of Hg2+ and Cr3+ in physiological conditions by a rhodamine
      derivative and its application as a reagent for cell-imaging studies.
AB  - A new rhodamine-based receptor, derivatized with an additional fluorophore
      (quinoline), was synthesized for selective recognition of Hg(2+) and Cr(3+) in an
      acetonitrile/HEPES buffer medium of pH 7.3. This reagent could be used as a dual
      probe and allowed detection of these two ions by monitoring changes in absorption
      and the fluorescence spectral pattern. In both instances, the extent of the
      changes was significant enough to allow visual detection. More importantly, the
      receptor molecule could be used as an imaging reagent for detection of Hg(2+) and
      Cr(3+) uptake in live human cancer cells (MCF7) using laser confocal microscopic
      studies. Unlike Hg(ClO(4))(2) or Hg(NO(3))(2) salts, HgCl(2) or HgI(2) failed to
      induce any visually detectable change in color or fluorescence upon interaction
      with L(1) under identical experimental conditions. Presumably, the higher
      covalent nature of Hg(II) in HgCl(2) or HgI(2) accounts for its lower acidity and
      its inability to open up the spirolactam ring of the reagent L(1). The issue has
      been addressed on the basis of the single-crystal X-ray structures of L(1).HgX(2)
      (X(-) = Cl(-) or I(-)) and results from other spectral studies.

PMID- 22148835
TI  - Two-order targeted brain tumor imaging by using an optical/paramagnetic nanoprobe
      across the blood brain barrier.
AB  - Surgical resection is a mainstay of brain tumor treatments. However, the
      completed excision of malignant brain tumor is challenged by its infiltrative
      nature. Contrast enhanced magnetic resonance imaging is widely used for defining
      brain tumor in clinic. However its ability in tumor visualization is hindered by
      the transient circulation lifetime, nontargeting specificity, and poor blood
      brain barrier (BBB) permeability of the commercially available MR contrast
      agents. In this work, we developed a two-order targeted nanoprobe in which
      MR/optical imaging reporters, tumor vasculature targeted cyclic [RGDyK] peptides,
      and BBB-permeable Angiopep-2 peptides are labeled on the PAMAM-G5 dendrimer. This
      nanoprobe is supposed to first target the alpha(V)beta(3) integrin on tumor
      vasculatures. Increased local concentration of nanoprobe facilitates the
      association between BBB-permeable peptides and the low-density lipoprotein
      receptor-related protein (LRP) receptors on the vascular endothelial cells, which
      further accelerates BBB transverse of the nanoprobe via LRP receptor-mediated
      endocytosis. The nanoprobes that have penetrated the BBB secondly target the
      brain tumor because both alpha(V)beta(3) integrin and LRP receptor are highly
      expressed on the tumor cells. In vivo imaging studies demonstrated that this
      nanoprobe not only efficiently crossed intact BBB in normal mice, but also
      precisely delineated the boundary of the orthotropic U87MG human glioblastoma
      xenograft with high target to background signal ratio. Overall, this two-order
      targeted nanoprobe holds the promise to noninvasively visualize brain tumors with
      uncompromised BBB and provides the possibility for real-time optical-image-guided
      brain tumor resection during surgery.

PMID- 22148837
TI  - Role of Rydberg states in the photochemical dynamics of ethylene.
AB  - We use the ab initio multiple spawning method with potential energy surfaces and
      nonadiabatic coupling vectors computed from multistate multireference
      perturbation theory (MSPT2) to follow the dynamics of ethylene after
      photoexcitation. We introduce an analytic formulation for the nonadiabatic
      coupling vector in the context of MSPT2 calculations. We explicitly include the
      low-lying 3s Rydberg state which has been neglected in previous ab initio
      molecular dynamics studies of this process. We find that although the 3s Rydberg
      state lies below the optically bright pipi* state, little population gets trapped
      on this state. Instead, the 3s Rydberg state is largely a spectator in the
      photodynamics, with little effect on the quenching mechanism or excited state
      lifetime. We predict the time-resolved photoelectron spectrum for ethylene and
      point out the signature of Rydberg state involvement that should be easily
      observed.

PMID- 22148836
TI  - Cyclostreptin derivatives specifically target cellular tubulin and further map
      the paclitaxel site.
AB  - Cyclostreptin is the first microtubule-stabilizing agent whose mechanism of
      action was discovered to involve formation of a covalent bond with tubulin.
      Treatment of cells with cyclostreptin irreversibly stabilizes their microtubules
      because cyclostreptin forms a covalent bond to beta-tubulin at either the T220 or
      the N228 residue, located at the microtubule pore or luminal taxoid binding site,
      respectively. Because of its unique mechanism of action, cyclostreptin overcomes
      P-glycoprotein-mediated multidrug resistance in tumor cells. We used a series of
      reactive cyclostreptin analogues, 6-chloroacetyl-cyclostreptin, 8-chloroacetyl
      cyclostreptin, and [(14)C-acetyl]-8-acetyl-cyclostreptin, to characterize the
      cellular target of the compound and to map the binding site. The three analogues
      were cytotoxic and stabilized microtubules in both sensitive and multidrug
      resistant tumor cells. In both types of cells, we identified beta-tubulin as the
      only or the predominantly labeled cellular protein, indicating that covalent
      binding to microtubules is sufficient to prevent drug efflux mediated by P
      glycoprotein. 6-Chloroacetyl-cyclostreptin, 8-chloroacetyl-cyclostreptin, and 8
      acetyl-cyclostreptin labeled both microtubules and unassembled tubulin at a
      single residue of the same tryptic peptide of beta-tubulin as was labeled by
      cyclostreptin (219-LTTPTYGDLNHLVSATMSGVTTCLR-243), but labeling with the
      analogues occurred at different positions of the peptide. 8-Acetyl-cyclostreptin
      reacted with either T220 or N228, as did the natural product, while 8
      chloroacetyl-cyclostreptin formed a cross-link to C241. Finally, 6-chloroacetyl
      cyclostreptin reacted with any of the three residues, thus labeling the pathway
      for cyclostreptin-like compounds, leading from the pore where these compounds
      enter the microtubule to the luminal binding pocket.

PMID- 22148838
TI  - Bivalent Smac mimetics with a diazabicyclic core as highly potent antagonists of
      XIAP and cIAP1/2 and novel anticancer agents.
AB  - Nonpeptidic, bivalent Smac mimetics designed based upon monovalent Smac mimetics
      with a diazabicyclic core structure bind to XIAP, cIAP1, and cIAP2 with low to
      subnanomolar affinities and are highly effective in antagonizing XIAP in cell
      free functional assays. They efficiently induce the degradation of cIAP1 and
      cIAP2 in cancer cells at concentrations as low as 1 nM, activate caspase-3 and 
      8, and cleave PARP at 3-10 nM. The most potent compounds in the series have
      IC(50) of 3-5 nM in inhibition of cell growth in both MDA-MB-231 and SK-OV-3 cell
      lines and are promising lead compounds for the development of a new class of
      cancer therapy.

PMID- 22148840
TI  - Phase behavior of binary blends of diblock copolymer/homopolymer confined in
      spherical nanopores.
AB  - Binary blends of a diblock copolymer (AB) and an incompatible homopolymer (C)
      confined in spherical cavities are studied using a simulated annealing technique.
      The phase behavior of the blends is examined for four typical cases, representing
      the different selectivity of the pore surface to the A, B, and C species. The
      internal morphology of the spherical polymeric particles is controlled by the
      homopolymer volume fraction, the degree of confinement, and the composition of
      the copolymer. Inside a particle, the homopolymers segregate to form one or,
      under some conditions, two domains; thus, the homopolymers may act as an
      additional controlling parameter of the shape and symmetry of the copolymer
      domain. A rich array of confinement-induced novel diblock copolymer morphologies
      is predicted. In particular, core-shell particles with the copolymers as the
      shell wrapping around a homopolymer core or a copolymer-homopolymer combined core
      and Janus-like particles with the copolymers and the homopolymers on different
      sides are obtained.

PMID- 22148839
TI  - Automated protein-ligand interaction screening by mass spectrometry.
AB  - Identifying protein-ligand binding interactions is a key step during early-stage
      drug discovery. Existing screening techniques are often associated with drawbacks
      such as low throughput, high sample consumption, and dynamic range limitations.
      The increasing use of fragment-based drug discovery (FBDD) demands that these
      techniques also detect very weak interactions (mM K(D) values). This paper
      presents the development and validation of a fully automated screen by mass
      spectrometry, capable of detecting fragment binding into the millimolar K(D)
      range. Low sample consumption, high throughput, and wide dynamic range make this
      a highly attractive, orthogonal approach. The method was applied to screen 157
      compounds in 6 h against the anti-apoptotic protein target Bcl-x(L). Mass
      spectrometry results were validated using STD-NMR, HSQC-NMR, and ITC experiments.
      Agreement between techniques suggests that mass spectrometry offers a powerful,
      complementary approach for screening.

PMID- 22148841
TI  - Spider silk inspired functional microthreads.
AB  - We employ the adhesive web building strategy used by modern orb-weaving spiders
      to produce functional microthreads that are similar in structure (beads-on-a
      string (BOAS) morphology) and adhesive properties to the capture-silk threads of
      the spider web. The diameter and spacing of droplets (beads) are controlled by
      varying the viscosity, velocity, and surface tension of the coating fluid. Using
      these functional threads, we also describe the behavior of the BOAS morphology
      during contact (mimicking the collision of an insect with the web) and during
      separation (mimicking insect rescue from the web). Our results show that the BOAS
      structure performs better than a cylindrical structure for adhesion, which may
      explain why this morphology is so prevalent in spider webs despite the cost of
      increasing the visibility of the web.

PMID- 22148842
TI  - Evaluation of the energetics of the concerted acid-base mechanism in enzymatic
      catalysis: the case of ketosteroid isomerase.
AB  - Structures of enzymes invariably reveal the proximity of acidic and basic
      residues to reactive sites on the substrate, so it is natural and common to
      suggest that enzymes employ concerted mechanisms to catalyze their difficult
      reactions. Ketosteroid isomerase (KSI) has served as a paradigm of enzymatic
      proton transfer chemistry, and its catalytic effect has previously been
      attributed to concerted proton transfer. We employ a specific inhibitor that
      contains an IR probe that reports directly and quantitatively on the ionization
      state of the ligand when bound in the active site of KSI. Measurement of the
      fractional ionization provides a missing link in a thermodynamic cycle that can
      discriminate the free energy advantage of a concerted versus nonconcerted
      mechanism. It is found that the maximum thermodynamic advantage that KSI could
      capture from a concerted mechanism (DeltaDeltaG degrees  = 0.5 kcal mol(-1)) is
      quite small.

PMID- 22148845
TI  - The Hartford impact on the care of older adults in transition.

PMID- 22148847
TI  - Anisotropy of chemical bonds in collagen molecules studied by X-ray absorption
      near-edge structure (XANES) spectroscopy.
AB  - Collagen type I fibrils are the major building blocks of connective tissues.
      Collagen fibrils are anisotropic supramolecular structures, and their orientation
      can be revealed by polarized light microscopy and vibrational microspectroscopy.
      We hypothesized that the anisotropy of chemical bonds in the collagen molecules,
      and hence their orientation, might also be detected by X-ray photoemission
      electron spectromicroscopy (X-PEEM) and X-ray absorption near-edge structure
      (XANES) spectroscopy, which use linearly polarized synchrotron light. To test
      this hypothesis, we analyzed sections of rat-tail tendon, composed of parallel
      arrays of collagen fibrils. The results clearly indicate that XANES-PEEM is
      sensitive to collagen fibril orientation and, more specifically, to the
      orientations of carbonyl and amide bonds in collagen molecules. These data
      suggest that XANES-PEEM is a promising technique for characterizing the chemical
      composition and structural organization at the nanoscale of collagen-based
      connective tissues, including tendons, cartilage, and bone.

PMID- 22148848
TI  - Analysis of preload-dependent reversible mechanical interlocking using beetle
      inspired wing locking device.
AB  - We report an analysis of preload-dependent reversible interlocking between
      regularly arrayed, high aspect ratio (AR) polymer micro- and nanofibers. Such a
      reversible interlocking is inspired from the wing-locking device of a beetle
      where densely populated microhairs (termed microtrichia) on the cuticular surface
      form numerous hair-to-hair contacts to maximize lateral shear adhesion. To mimic
      this, we fabricate various high AR, vertical micro- and nanopillars on a flexible
      substrate and investigate the shear locking force with different preloads (0.1-10
      N/cm(2)). A simple theoretical model is developed based on the competition
      between van der Waals (VdW) attraction and deflection forces of pillars, which
      can explain the preload-dependent maximum deflection, tilting angle, and total
      shear adhesion force.

PMID- 22148849
TI  - Probing the copper(II) binding features of angiogenin. Similarities and
      differences between a N-terminus peptide fragment and the recombinant human
      protein.
AB  - The angiogenin protein (hAng) is a potent angiogenic factor and its cellular
      activities may be affected by copper ions even if it is yet unknown how this
      metal ion is able to produce this effect. Among the different regions of hAng
      potentially able to bind copper ions, the N-terminal domain appears to be an
      ideal candidate. Copper(II) complexes of the peptide fragments encompassing the
      amino acid residues 4-17 of hAng protein were characterized by potentiometric, UV
      vis, CD, and EPR spectroscopic methods. The results show that these fragments
      have an unusual copper(II) binding ability. At physiological pH, the prevailing
      complex species formed by the peptide encompassing the protein sequence 4-17 is
      [CuHL], in which the metal ion is bound to two imidazole and two deprotonated
      amide nitrogen atoms disposed in a planar equatorial arrangement. Preliminary
      spectroscopic (UV-vis, CD, and EPR) data obtained on the copper(II) complexes
      formed by the whole recombinant hAng protein, show a great similarity with those
      obtained for the N-terminal peptide fragments. These findings indicate that
      within the N-terminal domain there is one of the preferred copper(II) ions
      anchoring site of the whole recombinant hAng protein.

PMID- 22148850
TI  - Total synthesis of (-)-tirandamycin C.
AB  - Tirandamycin C is a newly isolated member of the tetramic acid family natural
      products. We described herein the first enantioselective synthesis of natural (-)
      tirandamycin C, the postulated biosynthetic precursor of other members of this
      family. The highly stereoselective (>15:1) mismatched double asymmetric gamma
      stannylcrotylboration reaction of aldehyde 8 with crotylborane reagent (R)-E-9
      was utilized to access the key anti,anti-stereotriad 18.

PMID- 22148851
TI  - Nanomechanical silicon resonators with intrinsic tunable gain and sub-nW power
      consumption.
AB  - Nanoelectromechanical systems (NEMS) as integrated components for ultrasensitive
      sensing, time keeping, or radio frequency applications have driven the search for
      scalable nanomechanical transduction on-chip. Here, we present a hybrid silicon
      on-insulator platform for building NEM oscillators in which fin field effect
      transistors (FinFETs) are integrated into nanomechanical silicon resonators. We
      demonstrate transistor amplification and signal mixing, coupled with mechanical
      motion at very high frequencies (25-80 MHz). By operating the transistor in the
      subthreshold region, the power consumption of resonators can be reduced to record
      low nW levels, opening the way for the parallel operation of hundreds of
      thousands of NEM oscillators. The electromechanical charge modulation due to the
      field effect in a resonant transistor body constitutes a scalable nanomechanical
      motion detection all-on-chip and at room temperature. The new class of tunable
      NEMS represents a major step toward their integration in resonator arrays for
      applications in sensing and signal processing.

PMID- 22148853
TI  - Correction to "Double-roaming dynamics in CH3CHO dissociation".

PMID- 22148852
TI  - In-channel electrochemical detection in the middle of microchannel under high
      electric field.
AB  - We propose a new method for performing in-channel electrochemical detection under
      a high electric field using a polyelectrolytic gel salt bridge (PGSB) integrated
      in the middle of the electrophoretic separation channel. The finely tuned
      placement of a gold working electrode and the PGSB on an equipotential surface in
      the microchannel provided highly sensitive electrochemical detection without any
      deterioration in the separation efficiency or interference of the applied
      electric field. To assess the working principle, the open circuit potentials
      between gold working electrodes and the reference electrode at varying distances
      were measured in the microchannel under electrophoretic fields using an
      electrically isolated potentiostat. In addition, "in-channel" cyclic voltammetry
      confirmed the feasibility of electrochemical detection under various strengths of
      electric fields (~400 V/cm). Effective separation on a microchip equipped with a
      PGSB under high electric fields was demonstrated for the electrochemical
      detection of biological compounds such as dopamine and catechol. The proposed "in
      channel" electrochemical detection under a high electric field enables wider
      electrochemical detection applications in microchip electrophoresis.

PMID- 22148854
TI  - Scanning evanescent fields using a pointlike light source and a nanomechanical
      DNA gear.
AB  - The characterization of three-dimensional inhomogeneous illumination fields is a
      challenge in modern microscopy. Here we use a four-arm DNA junction as a
      nanomechanical translation stage to move a single fluorescent quantum dot through
      an exponentially decaying evanescent field. Recording the emission of the quantum
      dot within the evanescent field as well as under homogeneous illumination allows
      one to directly obtain the intensity distribution of the excitation field without
      additional deconvolution. Our method will allow the characterization of a broad
      range of illumination fields and to study near-field effects between small
      optical probes.

PMID- 22148855
TI  - Biomarker-mediated disruption of coffee-ring formation as a low resource
      diagnostic indicator.
AB  - The ring pattern resulting from the unique microfluidics in an evaporating coffee
      drop is a well-studied mass transport phenomenon generating interest in the
      research community mostly from a mechanistic perspective. In this report, we
      describe how biomarker-induced particle-particle assemblies, magnetic separation,
      and evaporation-driven ring formation can be combined for simple pathogen
      detection. In this assay design, the presence of biomarkers causes self-assembly
      of a magnetic nanoparticle and a fluorescently labeled micrometer-sized particle.
      A small spherical magnet under the center of the drop prevents these assemblies
      from migrating to the drop's edge while a nonreactive control particle flows to
      the edge forming a ring pattern. Thus the presence or absence of biomarker
      results in distinctly different distributions of particles in the dried drop.
      Proof-of-principle studies using poly-L-histidine, a peptide mimic of the malaria
      biomarker pfHRPII, show that the predicted particle distributions occur with a
      limit of detection of approximately 200-300 nM.

PMID- 22148856
TI  - High-performance graphene oxide electromechanical actuators.
AB  - Having demonstrated unparalleled actuation stresses and strains, covalently
      bonded carbon-based nanomaterials are emerging as the actuators of the future. To
      exploit their full potential, further investigations into the optimum
      configurations of these new materials are essential. Using first-principle
      density functional calculations, we examine so-called clamped and unzipped
      graphene oxide (GO) as potential electromechanical actuator materials. Very high
      strains are predicted for hole injection into GO, with reversible and
      irreversible values of up to 6.3% and 28.2%, respectively. The huge 28%
      irreversible strain is shown to be the result of a change in the atomic structure
      of GO from a metastable clamped to more stable unzipped configuration.
      Significantly, this strain generation mechanism makes it possible to hold a
      constant strain of 23.8% upon removal of the input power, making this material
      ideal for long-term, low-power switching applications. A unique contraction of
      unzipped GO upon electron injection is also observed. It is shown that the origin
      of this unique behavior is the modulation of the structural rippling effect,
      which is a characteristic feature of GO. With reversible strains and stresses in
      excess of 5% and 100 GPa, respectively, GO is poised to be an extremely useful
      material for micro/nanoelectromechanical system actuators.

PMID- 22148857
TI  - The boundary lubrication of chemically grafted and cross-linked hyaluronic acid
      in phosphate buffered saline and lipid solutions measured by the surface forces
      apparatus.
AB  - High molecular weight hyaluronic acid (HA) is present in articular joints and
      synovial fluid at high concentrations; yet despite numerous studies, the role of
      HA in joint lubrication is still not clear. Free HA in solution does not appear
      to be a good lubricant, being negatively charged and therefore repelled from most
      biological, including cartilage, surfaces. Recent enzymatic experiments suggested
      that mechanically or physically (rather than chemically) trapped HA could
      function as an "adaptive" or "emergency" boundary lubricant to eliminate wear
      damage in shearing cartilage surfaces. In this work, HA was chemically grafted to
      a layer of self-assembled amino-propyl-triethoxy-silane (APTES) on mica and then
      cross-linked. The boundary lubrication behavior of APTES and of chemically
      grafted and cross-linked HA in both electrolyte and lipid 1,2-dioleoyl-sn-glycero
      3-phosphocholine (DOPC) solutions was tested with a surface forces apparatus
      (SFA). Despite the high coefficient of friction (COF) of MU ~ 0.50, the
      chemically grafted HA gel significantly improved the lubrication behavior of HA,
      particularly the wear resistance, in comparison to free HA. Adding more DOPC
      lipid to the solution did not improve the lubrication of the chemically grafted
      and cross-linked HA layer. Damage of the underlying mica surface became visible
      at higher loads (pressure >2 MPa) after prolonged sliding times. It has generally
      been assumed that damage caused by or during sliding, also known as "abrasive
      friction", which is the main biomedical/clinical/morphological manifestation of
      arthritis, is due to a high friction force and, therefore, a large COF, and that
      to prevent surface damage or wear (abrasion) one should therefore aim to reduce
      the COF, which has been the traditional focus of basic research in
      biolubrication, particularly in cartilage and joint lubrication. Here we combine
      our results with previous ones on grafted and cross-linked HA on lipid bilayers,
      and lubricin-mediated lubrication, and conclude that for cartilage surfaces, a
      high COF can be associated with good wear protection, while a low COF can have
      poor wear resistance. Both of these properties depend on how the lubricating
      molecules are attached to and organized at the surfaces, as well as the structure
      and mechanical, viscoelastic, elastic, and physical properties of the surfaces,
      but the two phenomena are not directly or simply related. We also conclude that
      to provide both the low COF and good wear protection of joints under
      physiological conditions, some or all of the four major components of joints-HA,
      lubricin, lipids, and the cartilage fibrils-must act synergistically in ways
      (physisorbed, chemisorbed, grafted and/or cross-linked) that are still to be
      determined.

PMID- 22148858
TI  - Role of NH3 in the dehydrogenation of calcium amidoborane ammoniate and magnesium
      amidoborane ammoniate: a first-principles study.
AB  - First-principles calculations show that [NH(3)] molecules play crucial roles as
      both activator for the break-up of B-H bond and supplier of protic H for the
      establishment of dihydrogen bonding, which could facilitate the dehydrogenation
      of Ca(NH(2)BH(3))(2).2NH(3) or Mg(NH(2)BH(3))(2).NH(3) occurring at lower
      temperatures compared to those of Ca(NH(2)BH(3))(2) and Mg(NH(2)BH(3))(2).
      Moreover, the calculations of Helmholtz Free energy and [NH(3)] molecule removal
      energy evidence that coordination between [NH(3)] and Mg cation is stronger than
      that between [NH(3)] and Ca cation; therefore, Mg(NH(2)BH(3))(2).NH(3) will
      undergo directly dehydrogenation rather than deammoniation at lower temperatures.

PMID- 22148859
TI  - Novel 1,3-dipropyl-8-(3-benzimidazol-2-yl-methoxy-1-methylpyrazol-5-yl)xanthines
      as potent and selective A2B adenosine receptor antagonists.
AB  - Molecular modeling studies, including the comparative molecular field analysis
      (CoMFA) method, on 52 antagonists of the A(2B) adenosine receptor with known
      biological activity were performed to identify the three-dimensional features
      responsible for A(2B) adenosine receptor antagonist activity. On the basis of
      these and previous results on the potent antagonist effect of 8-pyrazolyl
      xanthines at human A(2B)AR, a new series of compounds was synthesized and
      evaluated in binding studies against the human A(1), A(2A), A(3), and A(2B)ARs. A
      remarkable improvement in selectivity with respect to the previous series,
      maintaining the potency at human A(2B) receptor, was achieved, as exemplified by
      the 8-[3-(4-chloro-6-trifluoromethyl-1H-benzoimidazol-2-yl-methoxy)-1-methyl-1H
      pyrazol-5-yl]-1,3-dipropyl-3,7-dihydro-purine-2,6-dione derivative 66: K(i) A(2B)
      = 9.4 nM, IC(50) hA(2B) = 26 nM hA(1)/hA(2B) = 269, hA(2A)/hA(2B) > 106,
      hA(3)/hA(2B) >106. This study also led to the identification of a series of
      pyrazole-xanthine compounds with a simplified structure, exemplified by 8-(3
      hydroxy-1-methyl-1H-pyrazol-5-yl)-xanthine 80 displaying very high affinity at
      A(2B)AR with good selectivity over AR subtypes (K(i) = 4.0 nM, IC(50) hA(2B) = 20
      nM hA(1)/hA(2B) = 183, hA(2A),hA(3)/hA(2B) > 250).

PMID- 22148860
TI  - Effects of the val(158)met catechol-O-methyltransferase gene polymorphism on
      olfactory processing in schizophrenia.
AB  - The catechol-O-methyltransferase (COMT) val158met polymorphism has received
      attention in schizophrenia due to its role in prefrontal dopamine catabolism.
      Given the rich dopaminergic innervations of the olfactory bulb and the influence
      of dopamine on the transmission of olfactory signals, the authors examined the
      influence of COMT genotype status on the olfactory processing impairment observed
      in schizophrenia. The University of Pennsylvania Smell Identification Test was
      administered unirhinally to individuals with schizophrenia (n = 42) and a
      demographically matched sample of healthy controls (n = 30). Individuals were
      genotyped for the COMT val158met polymorphism. A statistically significant
      interaction of diagnosis and COMT genotype was observed, such that schizophrenia
      heterozygotes and Met homozygotes showed impaired odor identification accuracy
      relative to Val158 homozygotes. These findings could not be explained by factors
      such as antipsychotic medication status, clinical symptomatology, or demographic
      and illness characteristics. Notably, the schizophrenia Val158 homozygotes' odor
      identification performance was comparable to that of the control group. These
      data indicate that odor identification impairments observed in schizophrenia are
      influenced by the COMT val158met polymorphism. This relationship is consistent
      with specific dopaminergic modulation of primary olfactory sensory afferents,
      rather than a broader effect on cognitive processes. Future studies that examine
      the olfactory processing deficit in schizophrenia with respect to other olfactory
      measures and COMT haplotypes is warranted.

PMID- 22148861
TI  - Direct hydride shift mechanism and stereoselectivity of P450nor confirmed by
      QM/MM calculations.
AB  - Nitric oxide reductase (P450(nor)) found in  Fusarium oxysporum  catalyzes the
      reduction of nitric oxide to N(2)O in a multistep process. The reducing agent,
      NADH, is bound in the distal pocket of the enzyme, and direct hydride transfer
      occurs from NADH to the nitric oxide bound heme enzyme, forming intermediate I.
      Here we studied the possibility of hydride transfer from NADH to both the
      nitrogen and oxygen of the heme-bound nitric oxide, using quantum chemical and
      combined quantum mechanics/molecular mechanics (QM/MM) calculations, on two
      different protein models, representing both possible stereochemistries, a syn-
      and an anti-NADH arrangement. All calculations clearly favor hydride transfer to
      the nitrogen of nitric oxide, and the QM-only barrier and kinetic isotope effects
      are good agreement with the experimental values of intermediate I formation. We
      obtained higher barriers in the QM/MM calculations for both pathways, but hydride
      transfer to the nitrogen of nitric oxide is still clearly favored. The barriers
      obtained for the syn, Pro-R conformation of NADH are lower and show significantly
      less variation than the barriers obtained in the case of anti conformation. The
      effect of basis set and wide range of functionals on the obtained results are
      also discussed.

PMID- 22148862
TI  - Quantitative proteomics using stable isotope labeling with amino acids in cell
      culture reveals protein and pathway regulation in porcine circovirus type 2
      infected PK-15 cells.
AB  - The infection of host cells by porcine circovirus type 2 (PCV2) leads to
      extensive modulation of the gene expression levels of target cells. To uncover
      the pathogenesis and virus-host interactions of PCV2, a quantitative proteomic
      study using the stable isotope labeling with amino acids in cell culture (SILAC),
      coupled with mass spectrometry, was performed on PCV2-infected PK-15 cells. The
      SILAC-based approach identified 1341 proteins, 163 of which showed significant
      change in level at 72 h after infection (79 up-regulated and 84 down-regulated).
      The modulated proteins included a number of proteins involved in substrate
      transport, cytoskeletal changes, and the stress response. Changes in the
      expression levels of selected proteins were verified by Western blot analysis.
      Ingenuity Pathway Analysis was used to reveal protein and interactive pathway
      regulation in response to PCV2 infection. Functional network and pathway analyses
      could provide insights into the complexity and dynamics of virus-host cell
      interactions and may accelerate our understanding of the mechanisms of PCV2
      infection.

PMID- 22148864
TI  - Chemical biology of lipidated proteins.
AB  - Many signaling proteins such as the members of the Ras superfamily of GTPases are
      posttranslationally modified by covalent attachment of lipid groups, which is
      crucial for the correct localization and function of these proteins. Numerous
      lipidated proteins are oncogens often found mutated in several human cancers.
      Therefore, several therapeutic strategies have been developed based on the
      inhibition of the enzymes involved in these lipidation steps. Here, we will
      summarize the results on protein lipidation inhibition, mainly focusing on the
      small molecules targeting the isoprenylation and acylation of proteins.

PMID- 22148865
TI  - Enantioselective biomimetic total syntheses of katsumadain and katsumadain C.
AB  - Enantioselective total syntheses of katsumadain and katsumadain C were achieved
      concisely through a biomimetic approach. Assembly of styryl-2-pyranone (3) and
      monoterpene 6 via acid-promoted regio- and stereoselective C-C bond formation
      afforded katsumadain (2), which underwent the photoinduced [2 + 2] dimerization
      in a head-to-tail mode to furnish katsumadain C (1).

PMID- 22148866
TI  - Relapse of intravenous drug use triggered by enfuvirtide, a parenteral
      antiretroviral medication.
AB  - Fuzeon(r) (enfuvirtide; Hoffmann-LaRoche, Nutley, NJ) is a parenteral medication
      prescribed to antiretroviral-experienced HIV patients. Clinicians are frequently
      concerned when prescribing enfuvirtide to former drug addicts because of the risk
      of triggering relapse, however, no previous report has described this adverse
      event. We describe two HIV-infected patients, previously abstinent from injection
      drug use, who experienced relapse or near-relapse situations after starting
      treatment with enfuvirtide. Along with the concerns related to adherence and to
      injection site reactions, clinicians who prescribe enfuvirtide should consider
      and discuss the risk of triggering relapse among former or recovering drug
      addicts.

PMID- 22148867
TI  - Phytochemical diversity of cranberry (Vaccinium macrocarpon Aiton) cultivars by
      anthocyanin determination and metabolomic profiling with chemometric analysis.
AB  - Originally native to the eastern United States, American cranberry ( Vaccinium
      macrocarpon  Aiton, family Ericaceae) cultivation of native and hybrid varieties
      has spread across North America. Herein is reported the phytochemical diversity
      of five cranberry cultivars (Stevens, Ben Lear, Bergman, Pilgrim, and GH1)
      collected in the Greater Vancouver Regional District, by anthocyanin content and
      UPLC-TOF-MS metabolomic profiling. The anthocyanin content for biological
      replicates (n = 5) was determined as 7.98 +/- 5.83, Ben Lear; 7.02 +/- 1.75,
      Bergman; 6.05 +/- 2.51, GH1; 3.28 +/- 1.88, Pilgrim; and 2.81 +/- 0.81, Stevens.
      Using subtractive metabonomic algorithms 6481 compounds were found conserved
      across all varietals, with 136 (Ben Lear), 84 (Bergman), 91 (GH1), 128 (Pilgrim),
      and 165 (Stevens) unique compounds observed. Principal component analysis (PCA)
      did not differentiate varieties, whereas partial least-squares discriminate
      analysis (PLS-DA) exhibited clustering patterns. Univariate statistical
      approaches were applied to the data set, establishing significance of values and
      assessing quality of the models. Metabolomic profiling with chemometric analysis
      proved to be useful for characterizing metabonomic changes across cranberry
      varieties.

PMID- 22148868
TI  - Correlation of Fat Mass Index and Fat-Free Mass Index with percentage body fat
      and their association with hypertension among urban South Indian adult men and
      women.
AB  - BACKGROUND: The assessment of Fat Mass and Fat-Free Mass indices provides
      valuable information about changes in body composition. AIM: To identify cut-off
      points for Fat Mass Index (FMI) to predict an upper limit of percentage body fat
      of men (25%) and women (30%) for defining obesity and its association with
      hypertension. SUBJECTS AND METHODS: A total of 436 men and 596 women were
      included in the study. Fat mass was calculated using skin-fold measurements. FMI
      cut-off points to predict an upper limit of percentage body fat of 25% (men) and
      30% (women) for defining obesity were assessed using Receiver Operating
      Characteristic (ROC) curve analysis. RESULTS: ROC curve analysis indicated that
      the level of FMI was 6.59 kg/m(2) in men and 6.64 kg/m(2) in women at 25% and 30%
      body fat, respectively. Risk estimation for hypertension with FMI indicated high
      risk of hypertension in men (OR: 3.4, CI: 2.1-5.5) as well as in women (OR: 5.3,
      CI: 2.3-12.4). CONCLUSION: The level of FMI was 6.6 kg/m(2) in men and women
      predicted at upper limits of 25% and 30% body fat, respectively, for defining
      obesity.

PMID- 22148869
TI  - Cooperative hydrogen-bonding effects in silanediol catalysis.
AB  - The importance of cooperative hydrogen-bonding effects and SiOH-acidification is
      described for silanediol catalysis. NMR binding, X-ray, and computational studies
      provide support for a unique dimer resulting from silanediol self-recognition.
      The significance of this cooperative hydrogen-bonding is demonstrated using novel
      fluorinated silanediol catalysts for the addition of indoles and N,N-dimethyl-m
      anisidine to trans-beta-nitrostyrene.

PMID- 22148870
TI  - Cyclam functionalization through isocyanate insertion in Zr-N bonds.
AB  - The insertion of isocyanates in (Bn(2)Cyclam)ZrX(2) is regioselective;
      (Bn(2)Cyclam)Zr(OR)(2) produces urea-like moieties by the insertion of RN?C?O in
      the Zr-N(amido) bonds of the cyclam ring. Depending on the bulkiness of the
      isocyanate R groups, O- and N-bound ureates are formed.
      (Bn(2)Cyclam)Zr(NH(t)Bu)(2) reacts with MesN?C?O at the terminal Zr-N bonds.

PMID- 22148871
TI  - High occurrence of HIV-positive siblings due to repeated mother-to-child
      transmission in Brazil.
AB  - Pregnancies in women without knowledge of their HIV-positive status increase the
      risk of mother-to-child transmission, and of disease progression. This study
      aimed to characterize the frequency of multiple pregnancies and of HIV-positive
      children in the family, during HAART era. We analyzed data of a national
      multicenter cohort study among Brazilian children with AIDS diagnosed between
      1999 and 2002. In total, 945 children and their 928 mothers were included. Five
      hundred and ninety (64.6%) women had a history of multiple pregnancies, and 49.5%
      attended prenatal care (mean: 3.5 consultations; SD 3.6). In 483 child cases, HIV
      status of the sibling was known; 130 (26.9%) of these were infected with HIV. In
      38.5% of cases, the child with AIDS included in the cohort study was the first
      case in the family. Despite the overall positive results of the Brazilian control
      policy of HIV/AIDS, our study shows that HIV infection in pregnant women was
      often undetected and that consequently there was a high frequency of repeated HIV
      infected children. There is a need to improve comprehensive prenatal and
      postnatal care of Brazilian women. HIV-affected families are most vulnerable and
      should be targeted by specific control programs, preventing additional HIV
      infections in other children.

PMID- 22148872
TI  - The application of highly doped single-layer graphene as the top electrodes of
      semitransparent organic solar cells.
AB  - A single-layer graphene film with high conductance and transparency was realized
      by effective chemical doping. The conductance of single-layer graphene was
      increased for more than 400% when it was doped with Au nanoparticles and poly(3,4
      ethylenedioxythiophene): poly(styrene sulfonic acid). Then semitransparent
      organic solar cells based on poly(3-hexylthiophene) (P3HT) and phenyl-C61-butyric
      acid methyl ester (PCBM) were fabricated with single-layer graphene and indium
      tin oxide (ITO) as the top and bottom electrodes, respectively. The performance
      of the devices was optimized by tuning the active layer thickness and doping the
      single-layer graphene electrodes. The maximum efficiency of 2.7% was observed in
      the devices with the area of 20 mm(2) illuminated from graphene electrode under
      the AM1.5 solar simulator. It is notable that all of the devices showed higher
      efficiency from the graphene than ITO side, which was attributed to the better
      transmittance of the graphene electrodes. In addition, the influence of the
      active area of the organic solar cell on its photovoltaic performance was
      studied. We found that, when the active areas increased from 6 to 50 mm(2), the
      power conversion efficiencies decreased from 3% to 2.3% because of the increased
      series resistances and the decreased edge effect of the devices.

PMID- 22148873
TI  - Aqueous NaCl and CsCl solutions confined in crystalline slit-shaped silica
      nanopores of varying degree of protonation.
AB  - All-atom molecular dynamics simulations were conducted to study the dynamics of
      aqueous electrolyte solutions confined in slit-shaped silica nanopores of various
      degrees of protonation. Five degrees of protonation were prepared by randomly
      removing surface hydrogen atoms from fully protonated crystalline silica
      surfaces. Aqueous electrolyte solutions containing NaCl or CsCl salt were
      simulated at ambient conditions. In all cases, the ionic concentration was 1 M.
      The results were quantified in terms of atomic density distributions within the
      pores, and the self-diffusion coefficient along the direction parallel to the
      pore surface. We found evidence for ion-specific properties that depend on ion
      surface, water-ion, and only in some cases ion-ion correlations. The degree of
      protonation strongly affects the structure, distribution, and the dynamic
      behavior of confined water and electrolytes. Cl(-) ions adsorb on the surface at
      large degrees of protonation, and their behavior does not depend significantly on
      the cation type (either Na(+) or Cs(+) ions are present in the systems
      considered). The cations show significant ion-specific behavior. Na(+) ions
      occupy different positions within the pore as the degree of protonation changes,
      while Cs(+) ions mainly remain near the pore center at all conditions considered.
      For a given degree of protonation, the planar self-diffusion coefficient of Cs(+)
      is always greater than that of Na(+) ions. The results are useful for better
      understanding transport under confinement, including brine behavior in the
      subsurface, with important applications such as environmental remediation.

PMID- 22148874
TI  - Dynamical arrest, percolation, gelation, and glass formation in model
      nanoparticle dispersions with thermoreversible adhesive interactions.
AB  - We report an experimental study of the dynamical arrest transition for a model
      system consisting of octadecyl coated silica suspended in n-tetradecane from
      dilute to concentrated conditions spanning the state diagram. The dispersion's
      interparticle potential is tuned by temperature affecting the brush conformation
      leading to a thermoreversible model system. The critical temperature for
      dynamical arrest, T*, is determined as a function of dispersion volume fraction
      by small-amplitude dynamic oscillatory shear rheology. We corroborate this
      transition temperature by measuring a power-law decay of the autocorrelation
      function and a loss of ergodicity via fiber-optic quasi-elastic light scattering.
      The structure at T* is measured using small-angle neutron scattering. The
      scattering intensity is fit to extract the interparticle pair-potential using the
      Ornstein-Zernike equation with the Percus-Yevick closure approximation, assuming
      a square-well interaction potential with a short-range interaction (1% of
      particle diameter). (1)  The strength of attraction is characterized using the
      Baxter temperature (2)  and mapped onto the adhesive hard sphere state diagram.
      The experiments show a continuous dynamical arrest transition line that follows
      the predicted dynamical percolation line until phi ~ 0.41 where it subtends the
      predictions toward the mode coupling theory attractive-driven glass line. An
      alternative analysis of the phase transition through the reduced second virial
      coefficient B(2)* shows a change in the functional dependence of B(2)* on
      particle concentration around phi ~ 0.36. We propose this signifies the location
      of a gel-to-glass transition. The results presented herein differ from those
      observed for depletion flocculated dispersion of micrometer-sized particles in
      polymer solutions, where dynamical arrest is a consequence of multicomponent
      phase separation, suggesting dynamical arrest is sensitive to the physical
      mechanism of attraction.

PMID- 22148875
TI  - Molecular scale conductance photoswitching in engineered bacteriorhodopsin.
AB  - Bacteriorhodopsin (BR) is a robust light-driven proton pump embedded in the
      purple membrane of the extremophilic archae Halobacterium salinarium . Its
      photoactivity remains in the dry state, making BR of significant interest for
      nanotechnological use. Here, in a novel configuration, BR was depleted from most
      of its endogenous lipids and covalently and asymmetrically anchored onto a gold
      electrode through a strategically located and highly responsive cysteine
      mutation; BR has no indigenous cysteines. Chemisorption on gold was characterized
      by surface plasmon resonance, reductive striping voltammetry, ellipsometry, and
      atomic force microscopy (AFM). For the first time, the conductance of isolated
      protein trimers, intimately probed by conducting AFM, was reproducibly and
      reversibly switched under wavelength-specific conditions (mean resistance of 39
      +/- 12 MOmega under illumination, 137 +/- 18 MOmega in the dark), demonstrating a
      surface stability that is relevant to potential nanodevice applications.

PMID- 22148876
TI  - Proteomic analysis of microvesicles derived from human mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) have emerged as a promising means for treating
      degenerative or incurable diseases. Recent studies have shown that microvesicles
      (MVs) from MSCs (MSC-MVs) contribute to recovery of damaged tissues in animal
      disease models. Here, we profiled the MSC-MV proteome to investigate their
      therapeutic effects. LC-MS/MS analysis of MSC-MVs identified 730 MV proteins. The
      MSC-MV proteome included five positive and two variable known markers of MSCs,
      but no negative marker, as well as 43 surface receptors and signaling molecules
      controlling self-renewal and differentiation of MSCs. Functional enrichment
      analysis showed that cellular processes represented by the MSC-MV proteins
      include cell proliferation, adhesion, migration, and morphogenesis. Integration
      of MSC's self-renewal and differentiation-related genes and the proteome of MSC
      conditioned media (MSC-CM) with the MSC-MV proteome revealed potential MV protein
      candidates that can be associated with the therapeutic effects of MSC-MVs: (1)
      surface receptors (PDGFRB, EGFR, and PLAUR); (2) signaling molecules (RRAS/NRAS,
      MAPK1, GNA13/GNG12, CDC42, and VAV2); (3) cell adhesion (FN1, EZR, IQGAP1, CD47,
      integrins, and LGALS1/LGALS3); and (4) MSC-associated antigens (CD9, CD63, CD81,
      CD109, CD151, CD248, and CD276). Therefore, the MSC-MV proteome provides a
      comprehensive basis for understanding the potential of MSC-MVs to affect tissue
      repair and regeneration.

PMID- 22148877
TI  - Noninjection facile synthesis of Gram-scale highly luminescent CdSe multipod
      nanocrystals.
AB  - Nearly all reported approaches for synthesis of high quality CdSe nanocrystals
      (NCs) involved two steps of preparation of Cd or Se stock solution in advance and
      then mixing the two reactants via hot-injection in high temperature. In this
      manuscript, Gram-scale CdSe multipod NCs were facilely synthesized in a
      noninjection route with the use of CdO and Se powder directly as reactants in
      paraffin reaction medium containing small amount of oleic acid and
      trioctylphosphine. The influence of various experimental variables, including
      reaction temperature, nature and amount of surfactants, Cd-to-Se ratio, and the
      nature of reactants, on the morphology of the obtained CdSe NCs have been
      systematically investigated. After deposition of ZnS shell around the CdSe
      multipod NCs, the PL QY of the obtained CdSe/ZnS can be up to 85%. The reported
      noninjection preparation approach can satisfy the requirement of industrial
      production bearing the advantage of low-cost, reproducible, and scalable.
      Furthermore, this facile noninjection strategy provides a versatile route to
      large-scale preparation of other semiconductor NCs with multipod or other
      morphologies.

PMID- 22148879
TI  - A parenting intervention for childhood behavioral problems: a randomized
      controlled trial in disadvantaged community-based settings.
AB  - OBJECTIVE: A community-based randomized controlled trial (RCT) was conducted in
      urban areas characterized by high levels of disadvantage to test the
      effectiveness of the Incredible Years BASIC parent training program (IYBP) for
      children with behavioral problems. Potential moderators of intervention effects
      on child behavioral outcomes were also explored. METHOD: Families were included
      if the child (aged 32-88 months) scored above a clinical cutoff on the Eyberg
      Child Behavior Inventory (ECBI). Participants (n = 149) were randomly allocated
      on a 2:1 ratio to an intervention group (n = 103) or a waiting-list control group
      (n = 46). Child behavior, parenting skills, and parent well-being were assessed
      at baseline and 6 months later using parent-report and independent observations.
      An intention-to-treat analysis of covariance was used to examine postintervention
      differences between groups. RESULTS: Statistically significant differences in
      child disordered behavior favored the intervention group on the ECBI Intensity
      (effect size = 0.7, p < .001) and Problem subscales (effect size = 0.75, p <
      .001). Intervention effects on child hyperactive-inattentive behaviors and social
      competence, as well as parent competencies and well-being, were also found.
      Moderator analyses showed that the effects of the IYBP intervention on the
      primary child outcomes were not moderated by child or family demographic
      characteristics or risk factors. CONCLUSION: The results demonstrate the
      effectiveness of the IYBP in alleviating problem behavior among children and in
      improving well-being among families living in disadvantaged areas. The findings
      also highlight the importance of parental intervention in early childhood for
      parents and children most in need of support.

PMID- 22148878
TI  - Diagnosing ADHD in adolescence.
AB  - OBJECTIVE: This study examines adolescent-specific practical problems associated
      with current practice parameters for diagnosing attention-deficit/hyperactivity
      disorder (ADHD) to inform recommendations for the diagnosis of ADHD in
      adolescents. Specifically, issues surrounding the use of self- versus informant
      ratings, diagnostic threshold, and retrospective reporting of childhood symptoms
      were addressed. METHOD: Using data from the Pittsburgh ADHD Longitudinal Study
      (PALS), parent, teacher, and self-reports of symptoms and impairment were
      examined for 164 adolescents with a childhood diagnosis of ADHD (age M = 14.74
      years) and 119 demographically similar non-ADHD controls (total N = 283).
      RESULTS: Results indicated that 70% of the well-diagnosed childhood ADHD group
      continued to meet Diagnostic and Statistical Manual of Mental Disorders (4th ed.,
      text rev.; American Psychiatric Association, 2000) diagnostic criteria for ADHD
      in adolescence; however, an additional 17% possessed clinically significant
      impairment in adolescence but did not qualify for a current ADHD diagnosis. The
      optimal source of information was combined reports from the parent and a core
      academic teacher. Adolescents with ADHD met criteria for very few symptoms of
      hyperactivity/impulsivity, suggesting a need to revisit the diagnostic threshold
      for these items. Additionally, emphasis on impairment, rather than symptom
      threshold, improved identification of adolescents with a gold-standard childhood
      diagnosis of ADHD and persistent ADHD symptoms. Parent retrospective reports of
      baseline functioning, but not adolescent self-reports, were significantly
      correlated with reports collected at baseline in childhood. CONCLUSIONS:
      Recommendations are offered for diagnosing ADHD in adolescence based on these
      findings.

PMID- 22148881
TI  - The usefulness of gamma-glutamyltransferase as a marker of cardiovascular
      function in Africans and Caucasians: the SABPA study.
AB  - AIM: Serum gamma-glutamyltransferase (GGT) is increasingly regarded as a marker
      of vascular function. However, the usefulness of this marker is in dispute.
      Gender and ethnic differences, as well as the serum level range where
      correlations with vascular function will emerge, may complicate the usefulness of
      GGT. The aim is to compare correlations with markers of vascular function between
      African and Caucasian groups. METHODS: This cross-sectional target population
      study involved four groups of African and Caucasian men and women of 100
      participants each. Fasting lipids, GGT, C-reactive protein (CRP), reactive oxygen
      species, and glycosylated hemoglobin (HbA1c) were determined as well as blood
      pressure, carotid intima-media thickness (CIMT), and left ventricular
      hypertrophy. RESULTS: gamma-Glutamyltransferase levels were significantly higher
      in Africans compared with Caucasians and also higher in men than in women. gamma
      Glutamyltransferase correlated with triglycerides in all four groups and after
      adjusting the correlations sustained in the male groups but disappeared in women.
      Correlations existed between GGT and blood pressure, except for the African
      women. After adjustments, CIMT correlated with GGT in Caucasian men (r = 0.29; P
      < .01). Glycosylated hemoglobin was associated with GGT in Caucasian women (r =
      0.26; P = .01) as well as CRP (r = 0.36; P < .01). When the groups were divided
      into low and high GGT groups by median split, most of the correlations
      disappeared in the high GGT groups. CONCLUSIONS: Gender and ethnic-specific
      associations occurred regarding GGT and variables associated with cardiovascular
      function. With high levels of GGT the correlations diminished. The usefulness of
      GGT as a marker of vascular dysfunction seems limited.

PMID- 22148880
TI  - Antimalarial activity of 9a-N substituted 15-membered azalides with improved in
      vitro and in vivo activity over azithromycin.
AB  - Novel classes of antimalarial drugs are needed due to emerging drug resistance.
      Azithromycin, the first macrolide investigated for malaria treatment and
      prophylaxis, failed as a single agent and thus novel analogues were envisaged as
      the next generation with improved activity. We synthesized 42 new 9a-N
      substituted 15-membered azalides with amide and amine functionalities via simple
      and inexpensive chemical procedures using easily available building blocks. These
      compounds exhibited marked advances over azithromycin in vitro in terms of
      potency against Plasmodium falciparum (over 100-fold) and high selectivity for
      the parasite and were characterized by moderate oral bioavailability in vivo. Two
      amines and one amide derivative showed improved in vivo potency in comparison to
      azithromycin when tested in a mouse efficacy model. Results obtained for compound
      6u, including improved in vitro potency, good pharmacokinetic parameters, and in
      vivo efficacy higher than azithromycin and comparable to chloroquine, warrant its
      further development for malaria treatment and prophylaxis.

PMID- 22148882
TI  - Photoinversion of cisoid/transoid binaphthyls.
AB  - Axially chiral binaphthyl-azobenzene cyclic dyads in which the two moieties are
      connected by two linkers of different lengths were synthesized. In the case of
      benzylated-binaphthyl analogue 2b, photoirradiation resulted in a dramatic change
      of the CD spectrum and optical rotation. Experimental and theoretical analyses
      indicated that the dihedral angle of the two naphthalene rings is strongly
      coupled to the azobenzene photoisomerization; cis-azobenzene induces a transoid
      binaphthyl structure, while trans-azobenzene induces a cisoid-binaphthyl
      structure.

PMID- 22148883
TI  - Pd-catalyzed oxidative ortho-C-H borylation of arenes.
AB  - The development of a Pd-catalyzed oxidative ortho-C-H borylation with N
      arylbenzamides is reported. A modified dibenzylideneacetone (dba) ligand, a weak
      base, and a strong oxidant are critical for obtaining good yields. The reaction
      is tolerant of electron-deficient and electron-rich benzamides derived from
      readily available benzoic acids. The borylated products can be converted to
      various synthons via diverse transformations.

PMID- 22148884
TI  - Predictive model for diffusion-limited aggregation kinetics of nanocolloids under
      high concentration.
AB  - Smoluchowski's equation for the rate of aggregation of colloidal particles under
      diffusion-limited conditions has set the basis for the interpretation of kinetics
      of aggregation phenomena. Nevertheless, its use is limited to sufficiently dilute
      conditions. In this work we propose a correction to Smoluchowski's equation by
      using a result derived by Richards (  J. Phys. Chem.     1986  ,   85  ,   3520 
      ) within the framework of trapping theory. This corrected aggregation kernel,
      which accounts for concentration dependence effects, has been implemented in a
      population-balance equations scheme and used to model the aggregation kinetics of
      colloidal particles undergoing diffusion-limited aggregation under concentrated
      conditions (up to a particle volume fraction of 30%). The predictions of
      population balance calculations have been validated by means of Brownian dynamic
      simulations. It was found that the corrected kernel can very well reproduce the
      results from Brownian dynamic simulations for all concentration values
      investigated, and is also able to accurately predict the time required by a
      suspension to reach the gel point. On the other hand, classical Smoluchowski's
      theory substantially underpredicts the rate of aggregation as well as the onset
      of gelation, with deviations becoming progressively more severe as the particle
      volume fraction increases.

PMID- 22148885
TI  - Rhodium catalyzed chelation-assisted C-H bond functionalization reactions.
AB  - Over the last several decades, researchers have achieved remarkable progress in
      the field of organometallic chemistry. The development of metal-catalyzed cross
      coupling reactions represents a paradigm shift in chemical synthesis, and today
      synthetic chemists can readily access carbon-carbon and carbon-heteroatom bonds
      from a vast array of starting compounds. Although we cannot understate the
      importance of these methods, the required prefunctionalization to carry out these
      reactions adds cost and reduces the availability of the starting reagents.  The
      use of C-H bond activation in lieu of prefunctionalization has presented a
      tantalizing alternative to classical cross-coupling reactions. Researchers have
      met the challenges of selectivity and reactivity associated with the development
      of C-H bond functionalization reactions with an explosion of creative advances in
      substrate and catalyst design. Literature reports on selectivity based on steric
      effects, acidity, and electronic and directing group effects are now numerous. 
      Our group has developed an array of C-H bond functionalization reactions that
      take advantage of a chelating directing group, and this Account surveys our
      progress in this area. The use of chelation control in C-H bond functionalization
      offers several advantages with respect to substrate scope and application to
      total synthesis. The predictability and decreased dependence on the inherent
      stereoelectronics of the substrate generally result in selective and high
      yielding transformations with broad applicability. The nature of the chelating
      moiety can be chosen to serve as a functional handle in subsequent elaborations. 
      Our work began with the use of Rh(I) catalysts in intramolecular aromatic C-H
      annulations, which we further developed to include enantioselective
      transformations. The application of this chemistry to the simple olefinic C-H
      bonds found in alpha,beta-unsaturated imines allowed access to highly substituted
      olefins, pyridines, and piperidines. We observed complementary reactivity with
      Rh(III) catalysts and developed an oxidative coupling with unactivated alkenes.
      Further studies on the Rh(III) catalysts led us to develop methods for the
      coupling of C-H bonds to polarized pi bonds such as those in imines and
      isocyanates. In several cases the methods that we have developed for chelation
      controlled C-H bond functionalization have been applied to the total synthesis of
      complex molecules such as natural products, highlighting the utility of these
      methods in organic synthesis.

PMID- 22148886
TI  - Interactions between metal ions and carbohydrates. Spectroscopic characterization
      and the topology coordination behavior of erythritol with trivalent lanthanide
      ions.
AB  - The coordination of carbohydrate to metal ions is important because it may be
      involved in many biochemical processes. The synthesis and characterization of
      several novel lanthanide-erythritol complexes (TbCl(3).1.5C(4)H(10)O(4).H(2)O
      (TbE(I)), Pr(NO(3))(3).C(4)H(10)O(4).2H(2)O (PrEN),
      Ce(NO(3))(3).C(4)H(10)O(4).2H(2)O (CeEN), Y(NO(3))(3).C(4)H(10)O(4).C(2)H(5)OH
      (YEN), Gd(NO(3))(3).C(4)H(10)O(4).C(2)H(5)OH (GdEN)) and
      Tb(NO(3))(3).C(4)H(10)O(4).C(2)H(5)OH (TbEN) are reported. The structures of
      these complexes in the solid state have been determined by X-ray diffraction.
      Erythritol is used as two bidentate ligands or as three hydroxyl group donor in
      these complexes. FTIR spectra indicate that two kinds of structures, with water
      and without water involved in the coordination sphere, were observed for
      lanthanide nitrate-erythritol complexes. FIR and THz spectra show the formation
      of metal ion-erythritol complexes. Luminescence spectra of Tb-erythritol
      complexes have the characteristics of the Tb ion.

PMID- 22148887
TI  - Slow insertion kinetics during interaction of a model antimicrobial peptide with
      unilamellar phospholipid vesicles.
AB  - The mechanism of interaction between a model antimicrobial peptide and
      phospholipid unilamellar vesicle membranes was studied using fluorescence
      spectroscopy, fluorescence lifetime measurements, and light scattering. The
      peptide, a mellitin mutant, was labeled at position K14 with the polarity
      sensitive probe AlexaFluor 430. The kinetics of the interaction of this
      derivative with various concentrations of 1,2-dipalmitoyl-sn-glycero-3
      phosphatidylcholine (DPPC) vesicles was examined. Our work unveiled two novel
      aspects of peptide-lipid interactions. First, the AB plot or phasor analysis of
      the fluorescence lifetime studies revealed at least three different peptide
      states, the population of which depended on the lipid to peptide (L:P)
      concentration ratio. Second, complex fluorescence kinetics were observed over
      extended time-scales from 30 s to 2 h. The extended kinetics was only observed at
      particular lipid concentrations (L:P ratios 20:1 and 10:1) and not at others (30,
      40, 50 and 100:1 L:P ratio). Analysis of the complex kinetics revealed several
      intermediates. We assign these to distinct states of the peptide formed during
      helix insertion into the vesicle membrane that are intermediate to lytic pore
      formation.

PMID- 22148888
TI  - Hydrocarbon and fatty acid composition of cheese as affected by the pasture
      vegetation type.
AB  - The determination of the geographical origin of dairy products is an ongoing
      issue. In this paper the effects of botanical diversity of two pastures on the
      hydrocarbon and fatty acid composition of cheese fat were studied, over 2 years
      of experimentation. Two areas in the Italian southwestern Alpine region,
      dominated by  Trifolium alpinum  (T) and  Festuca nigrescens  (F) vegetation,
      respectively, were chosen, and milk obtained from cows grazing on these pastures
      was used to produce a semihard traditional cheese. Cheese samples showed a
      significantly different composition of most linear hydrocarbons, odd-chain (C15,
      C17, and C17:1) and unsaturated (trans-11,cis-15-C18:2, C18:3, C20:4n-6, C20:4n
      3, and 20:5n-3) fatty acids, according to pasture type. The ratio between C(29)
      and C(27) linear hydrocarbons, unlike the absolute content of the single
      molecules, showed a good discriminating ability between the two pastures and was
      little affected by the natural variability due to the climatic and environmental
      factors.

PMID- 22148889
TI  - Palladium-catalyzed direct ortho-alkynylation of aromatic carboxylic acid
      derivatives.
AB  - The palladium-catalyzed direct alkynylation of C-H bonds in aromatic carboxylic
      acid derivatives is described. The use of 8-aminoquinoline as a directing group
      facilitates the alkynylation of an electronically diverse range of C(sp(2))-H
      bonds.

PMID- 22148890
TI  - Electronic durability of flexible transparent films from type-specific single
      wall carbon nanotubes.
AB  - The coupling between mechanical flexibility and electronic performance is
      evaluated for thin films of metallic and semiconducting single-wall carbon
      nanotubes (SWCNTs) deposited on compliant supports. Percolated networks of type
      purified SWCNTs are assembled as thin conducting coatings on elastic polymer
      substrates, and the sheet resistance is measured as a function of compression and
      cyclic strain through impedance spectroscopy. The wrinkling topography,
      microstructure and transparency of the films are independently characterized
      using optical microscopy, electron microscopy, and optical absorption
      spectroscopy. Thin films made from metallic SWCNTs show better durability as
      flexible transparent conductive coatings, which we attribute to a combination of
      superior mechanical performance and higher interfacial conductivity.

PMID- 22148891
TI  - Tuning ion conducting pathways using holographic polymerization.
AB  - Polymer electrolyte membranes (PEMs) with high and controlled ionic conductivity
      are important for energy-related applications, such as solid-state batteries and
      fuel cells. Herein we disclose a new strategy to fabricate long-range ordered
      PEMs with tunable ion conducting pathways using a holographic polymerization (HP)
      method. By incorporating polymer electrolyte into the carefully selected HP
      system, electrolyte layers/channels with length scales of a few tens of
      nanometers to micrometers can be formed with controlled orientation and
      anisotropy; ionic conductivity anisotropy as high as 37 has been achieved.

PMID- 22148892
TI  - Cheese can reduce indexes that estimate fatty acid desaturation. Results from the
      Oslo Health Study and from experiments with human hepatoma cells.
AB  - Previously, cheese intake was shown to be inversely related to serum
      triglycerides, raising the possibility that cheese might inhibit triglyceride
      synthesis, which is governed by fatty acid desaturases. Therefore, analyses were
      done to study whether cheese intake was associated with indexes that reflect
      fatty acid desaturation in 121 healthy ethnic Norwegians aged 40-45 years, a
      subsample from the Oslo Health Study (N = 18 777). Experiments with human
      hepatoma cells (HepG2) were done to clarify whether cheese might have a causal
      effect on desaturases. Fatty acid distribution in lipids of human sera and HepG2
      cells was determined by gas chromatography. Delta9-Desaturase was estimated by
      the (16:1,n-7)/(16:0) and (18:1,n-9)/(18:0) ratios, abbreviated ds9_1 and ds9_2,
      and Delta5-desaturase (ds5) by the (20:4,n-6)/(18:2,n-6) ratio. Correlation,
      ANOVA, and multiple linear regression models were used to study associations.
      Oslo Health Study: Subjects with cheese intake >4-6 times per week had 33% lower
      ds9_1 and 16% lower ds5 than subjects with intake <= 4-6 times per week. The
      cheese intake vs. ds5 association prevailed when adjusting for sex, time since
      last meal, fatty fish, vegetables, fruit-berries, fruit juice, cod liver oil,
      coffee, alcohol, body mass index, physical activity, length of education, and
      smoking. HepG2 cells: An ethanol extract of Jarlsberg cheese lowered the
      desaturase indexes. Inhibition of ds9_1 increased with increasing amount cheese
      extract added. Thus, cheese may contain inhibitors of desaturases, thereby
      providing an explanation for the previously reported negative association between
      cheese intake and triglycerides.

PMID- 22148897
TI  - Efficacy and safety of oral strontium ranelate for the treatment of knee
      osteoarthritis: rationale and design of randomised, double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: The osteoporosis drug strontium ranelate dissociates bone remodelling
      processes. It also inhibits subchondral bone resorption and stimulates cartilage
      matrix formation in vitro. Exploratory studies in the osteoporosis trials report
      that strontium ranelate reduces biomarkers of cartilage degradation, and
      attenuates the progression and clinical symptoms of spinal osteoarthritis,
      suggesting symptom- and structure-modifying activity in osteoarthritis. We
      describe the rationale and design of a randomised trial evaluating the efficacy
      and safety of strontium ranelate in knee osteoarthritis. RESEARCH DESIGN,
      METHODS, AND RESULTS: This double-blind, placebo-controlled trial (98 centres, 18
      countries) includes ambulatory Caucasian men and women aged >=50 years with
      primary knee osteoarthritis of the medial tibiofemoral compartment (Kellgren and
      Lawrence grade 2 or 3), joint space width (JSW) 2.5 to 5 mm, and knee pain on
      most days in the previous month (intensity >=40 mm on a visual analogue scale).
      Patients are randomly allocated to three groups (strontium ranelate 1 or 2 g/day,
      or placebo). Follow-up is expected to last 3 years. The primary endpoint is
      radiographic change in JSW from baseline in each group versus placebo. The main
      clinical secondary endpoint is WOMAC score at the knee. Safety is assessed at
      every visit. It is estimated that 1600 patients are required to establish
      statistical significance with power >90% (0.2 mm +/- 10% between-group difference
      in change in JSW over 3 years). Recruitment started in April 2006. The results
      are expected in spring 2012. CLINICAL TRIAL REGISTRATION: The trial is registered
      on www.controlled-trials.com (number ISRCTN41323372). CONCLUSIONS: This
      randomised, double blind, placebo-controlled study will establish the potential
      of strontium ranelate in improving structure and symptoms in patients with knee
      osteoarthritis.

PMID- 22148898
TI  - Proteome of the early embryo-maternal dialogue in the cattle uterus.
AB  - We analyzed embryo-maternal interactions in the bovine uterus on day 8 of
      development. Proteomic profiles were obtained by two-dimensional difference gel
      electrophoresis from 8 paired samples of uterine fluid (UF) from the same animal
      with and without embryos in the uterus. Results were contrasted with UF obtained
      after artificial insemination. We detected 50 differential protein spots (t test,
      p < 0.05). Subsequent protein characterization by nano-LC-ESI-MS/MS enabled us to
      identify 38 proteins, obtaining for first time the earliest evidence of
      involvement of the down-regulated NFkB system in cattle as a pregnancy signature
      pathway. Embryos enhanced the embryotrophic ability of UF and decreased uterine
      protein, while blood progesterone was unaltered. Twinfilin, hepatoma-derived
      growth factor, and synaptotagmin-binding cytoplasmic RNA interacting protein have
      not previously been identified in the mammalian uterus. TNFalpha and IL-1B were
      localized to embryos by immunocytochemistry, and other proteins were validated by
      Western blot in UF. Glycosylated-TNFalpha, IL-1B, insulin, lactotransferrin,
      nonphosphorylated-peroxiredoxin, albumin, purine nucleoside phosphorylase, HSPA5,
      and NFkB were down-regulated, while phosphorylated-peroxiredoxin, annexin A4, and
      nonglycosylated-TNFalpha were up-regulated. The embryonic signaling agents
      involved could be TNFalpha and IL-1B, either alone or in a collective dialogue
      with other proteins. Such molecules might explain the immune privilege during
      early bovine development.

PMID- 22148899
TI  - Cystic fibrosis transmembrane conductance regulator mutations and polymorphisms
      associated with congenital bilateral absence of vas deferens in a restricted
      group of patients from North Africa.
AB  - BACKGROUND: Congenital bilateral absence of vas deferens (CBAVD) is responsible
      for 2-6% of male infertility. It occurs in 95% of men with cystic fibrosis. This
      malformation is present in patients with a sterile obstructive azoospermia but
      without clinical evidence of cystic fibrosis. Molecular study of the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene responsible for cystic
      fibrosis could show the relationship between this disease and bilateral absence
      of vas deferens. PATIENTS AND METHODS: The study involved 20 male patients aged
      between 28-40 years, referred with suspected cystic fibrosis and in whom
      bilateral absence of vas deferens was confirmed by cyto-biochemical analyses and
      urogenital ultrasound. Molecular study of the CFTR gene was based on several
      techniques: DHPLC, DGGE and direct sequencing. RESULTS: Thirteen patients had
      CFTR mutations: F508del, G542X, W1282X, E1104X, 711+1G -> T, V201M (TG) m and
      IVS8-5T. These mutations were associated with polymorphisms: M470V and D1270N.
      Seven cases presented only polymorphisms. CONCLUSION: The different mutations
      found in this study were associated with polymorphisms which decrease the
      severity of the disease and delay its onset. Thus, bilateral agenesis of the vas
      deferens is classed as a form of cystic fibrosis with only genital expression.

PMID- 22148900
TI  - Earthworm sublethal responses to titanium dioxide nanomaterial in soil detected
      by 1H NMR metabolomics.
AB  - 1H NMR-based metabolomics was used to examine the response of Eisenia fetida
      earthworms raised from juveniles for 20-23 weeks in soil spiked with either 20 or
      200 mg/kg of a commercially available uncoated titanium dioxide (TiO(2))
      nanomaterial (nominal diameter of 5 nm). To distinguish responses specific to
      particle size, soil treatments spiked with a micrometer-sized TiO(2) material
      (nominal diameter, <45 MUm) at the same concentrations (20 and 200 mg/kg) were
      also included in addition to an unspiked control soil. Multivariate statistical
      analysis of the (1)H NMR spectra for aqueous extracts of E. fetida tissue
      suggested that earthworms exhibited significant changes in their metabolic
      profile following TiO(2) exposure for both particle sizes. The observed earthworm
      metabolic changes appeared to be consistent with oxidative stress, a proposed
      mechanism of toxicity for nanosized TiO(2). In contrast, a prior study had
      observed no impairment of E. fetida survival, reproduction, or growth following
      exposure to the same TiO(2) spiked soils. This suggests that (1)H NMR-based
      metabolomics provides a more sensitive measure of earthworm response to TiO(2)
      materials in soil and that further targeted assays to detect specific cellular or
      molecular level damage to earthworms caused by chronic exposure to TiO(2) are
      warranted.

PMID- 22148901
TI  - Concentration-gradient-dependent ion current rectification in charged conical
      nanopores.
AB  - Ion current rectification (ICR) in negatively charged conical nanopores is shown
      to be controlled by the electrolyte concentration gradient depending on the
      direction of ion diffusion. The degree of ICR is enhanced with the increasing
      forward concentration difference. An unusual rectification inversion is observed
      when the concentration gradient is reversely applied. A numerical simulation
      based on the coupled Poisson and Nernst-Planck (PNP) equations is proposed to
      solve the ion distribution and ionic flux in the charged and structurally
      asymmetric nanofluidic channel with diffusive ion flow. Simulation results
      qualitatively describe the diffusion-induced ICR behavior in conical nanopores
      suggested by the experimental data. The concentration-gradient-dependent ICR
      enhancement and inversion is attributed to the cooperation and competition
      between geometry-induced asymmetric ion transport and the diffusive ion flow. The
      present study improves our understanding of the ICR in asymmetric nanofluidic
      channels associated with the ion concentration difference and provides insight
      into the rectifying biological ion channels.

PMID- 22148902
TI  - Repetition effects in grasping.
AB  - The task in the present experiments was to reach out and grasp a novel object
      that afforded two possible grips. Different versions of the object were created
      that biased subjects to use one grip or the other. The dependent variable was the
      repetition effect, the tendency to repeat the grip that was used on the previous
      trial. In Experiment 1, two qualitatively different objects were used, and it was
      found that the repetition effect was specific to the object being grasped: There
      was much less tendency to use the same grip as the previous trial if the object
      being grasped was different. Moreover, the effect lasted over intervening trials
      and was even present with more than five intervening trials. In Experiment 2, the
      global context was manipulated, so that in some blocks one grip was much more
      likely than the other. However, this manipulation had little effect on the choice
      of grip and did not interact with the repetition effect. In Experiment 3, the
      hand used to grasp the object was manipulated, and there was little change in the
      repetition effect. Thus, a grip was more likely to be used if it was used on the
      previous trial, regardless of whether the previous grasp was performed with the
      left or right hand. In Experiment 4, a similar result was found for a
      manipulation of object location and orientation. Our interpretation of these
      results is that subjects prepare for an action by retrieving action features from
      memory, and that the object to be grasped provides a critical cue for that memory
      retrieval. In this view, the repetition effect is essentially a memory recency
      effect.

PMID- 22148903
TI  - Orthographic versus semantic matching in visual search for words within lists.
AB  - An eye-tracking experiment was performed to assess the influence of orthographic
      and semantic distractor words on visual search for words within lists. The target
      word (e.g., "raven") was either shown to participants before the search (literal
      search) or defined by its semantic category (e.g., "bird", categorical search).
      In both cases, the type of words included in the list affected visual search
      times and eye movement patterns. In the literal condition, the presence of
      orthographic distractors sharing initial and final letters with the target word
      strongly increased search times. Indeed, the orthographic distractors attracted
      participants' gaze and were fixated for longer times than other words in the
      list. The presence of semantic distractors related to the target word also
      increased search times, which suggests that significant automatic semantic
      processing of nontarget words took place. In the categorical condition, semantic
      distractors were expected to have a greater impact on the search task. As
      expected, the presence in the list of semantic associates of the target word led
      to target selection errors. However, semantic distractors did not significantly
      increase search times any more, whereas orthographic distractors still did.
      Hence, the visual characteristics of nontarget words can be strong predictors of
      the efficiency of visual search even when the exact target word is unknown. The
      respective impacts of orthographic and semantic distractors depended more on the
      characteristics of lists than on the nature of the search task.

PMID- 22148904
TI  - Second-order relational face processing is applied to faces of different race and
      photographic contrast.
AB  - A large body of research suggests that faces are processed by a specialized
      mechanism within the human visual system. This specialized mechanism is made up
      of subprocesses (Maurer, LeGrand, & Mondloch, 2002). One subprocess, called
      second- order relational processing, analyzes the metric distances between face
      parts. Importantly, it is well established that other-race faces and contrast
      reversed faces are associated with impaired performance on numerous face
      processing tasks. Here, we investigated the specificity of second-order
      relational processing by testing how this process is applied to faces of
      different race and photographic contrast. Participants completed a feature
      displacement discrimination task, directly measuring the sensitivity to second
      order relations between face parts. Across three experiments we show that,
      despite absolute differences in sensitivity in some conditions, inversion
      impaired performance in all conditions. The presence of robust inversion effects
      for all faces suggests that second-order relational processing can be applied to
      faces of different race and photographic contrast.

PMID- 22148905
TI  - Self and near relative ratings of functional level one year after traumatic brain
      injury.
AB  - PURPOSE: To quantify traumatic brain injury (TBI) patients' perceptions of own
      function by the Patient Competency Rating Scale (PCRS) one year after injury, and
      to examine self-awareness of functional deficits by comparing PCRS ratings from
      patients (PCRS-P) and PCRS ratings from near relatives (PCRS-R), and to identify
      predictors of awareness deficits. METHOD: A cohort of 50 severe (n = 33) and
      moderate (n = 17) TBI patients. Awareness of deficits was investigated by
      subtracting PCRS relative ratings from PCRS patient ratings. Predictors of PCRS
      ratings and differences were assessed by stepwise multiple regression analyses.
      RESULTS: The average patient PCRS sum score was 122/150 (95% CI = 115; 129) as
      compared to a sum score of 117/150 (95% CI = 110; 125), given by their relatives
      (p = 0.93). The patients scored themselves slightly higher than their relatives
      in the domains of activities of daily living (ADL) and cognitive function (p <
      0.001, p < 0.001). Regression analyses showed that Glasgow Coma Scale (GCS)score
      at admission to rehabilitation was the strongest predictor of patient PCRS (B =
      3.314, p = 0.008). The strongest predictor of differences between patient and
      relative PCRS was GCS acute (B = -3.530, p = 0.001). CONCLUSIONS: TBI patients
      demonstrated a slight "awareness gap" in ADL and cognitive function. Low GCS in
      the acute phase and high age were the strongest predictors of self- awareness
      deficits.

PMID- 22148906
TI  - The effectiveness of graded activity in patients with non-specific low-back pain:
      a systematic review.
AB  - BACKGROUND: Non-specific low-back pain (LBP) is considered a major health and
      economic problem in Western society. Nowadays a common used intervention on non
      specific LBP is graded activity (GA). Graded Activity developed by Lindstrom et
      al., consisted of four parts: (i) measurements of functional capacity; (ii) a
      work-place visit; (iii) back school education and (iv) an individual, sub
      maximal, gradually increased exercise program with an operant-conditioning
      behavioural approach as described by Fordyce et al. OBJECTIVE: To evaluate the
      effectiveness of GA in adults with non-specific LBP on pain, disabilities and
      return to work. DATA SOURCES: An extensive literature search of PubMed, Embase,
      CINAHL and The Cochrane Library was conducted in July 2011. REVIEW METHODS:
      Randomized controlled trials (RCTs) evaluating the effect of GA in patients with
      non-specific LBP were eligible. Methodological quality of the studies was
      assessed according to the PEDro scale. A best-evidence synthesis was conducted
      according to van Peppen et al. to interpret the outcomes of the included studies.
      RESULTS: Ten articles were included in this systematic review; these articles
      described five RCTs (680 patients). The best-evidence synthesis revealed that
      there was no or insufficient evidence for a positive effect of GA on pain,
      disabilities and return to work in patients with non-specific LBP. CONCLUSION:
      Currently there is no or insufficient evidence that GA results in better outcomes
      of patients with non-specific LBP.

PMID- 22148908
TI  - A bis(heptafulvenyl)-dicyanoethylene thermoswitch with two sites for ring
      closure.
AB  - Suitably functionalized vinylheptafulvenes (VHFs) act as thermoswitches
      undergoing ring closure to the corresponding dihydroazulenes (DHAs). Here we
      present the synthesis of a new such thermoswitch incorporating two heptafulvene
      rings on a dicyanoethylene unit. The synthetic protocol explores both the
      tropylium species as an electrophile and as a leaving group in the generation of
      the heptafulvene units. The thermally induced ring closure was enhanced as a
      result of two accessible sites for the reaction to occur.

PMID- 22148909
TI  - Non-estrogen conventional and phytochemical treatments for vasomotor symptoms:
      what needs to be known for practice.
AB  - OBJECTIVE: Non-hormonal treatment for menopausal vasomotor symptoms (VMS) is
      needed in women in whom there are medical or personal concerns on the use of
      hormone therapy. This paper reviews conventional and phytochemical therapies
      available for the relief of VMS, on their mechanisms of action, their efficacy
      and safety concerns. METHODS: Medline was searched through Pubmed on the names of
      the diverse therapies analyzed, up to June 2011. The Cochrane Controlled Clinical
      Trials Register Database was searched for relevant trials that provided data on
      treatment of menopausal hot flushes. RESULTS: All non-estrogen treatments for VMS
      are less efficacious than estrogen treatment. Randomized trials with
      neuroendocrine agents show globally modest to moderate reduction of VMS and
      frequent bothersome adverse events. The variability of effects makes it possible
      to undergo treatment in search for individual response where estrogen treatment
      is contraindicated. The antidepressants that interact with cytochrome P450,
      inhibiting tamoxifen metabolism to endoxifen, interfere with tamoxifen therapy in
      breast cancer patients. Otherwise, botanical products containing isoflavones from
      soy bean or red clover have great variability in bioavailability, have a broader
      spectrum of action than estradiol, and have predominant estrogen receptor-b
      activity. The efficacy of phytoestrogens on VMS is similar to placebo. They
      should be avoided in women with breast cancer and, in particular, in women being
      treated with tamoxifen or aromatase inhibitors due to possible antagonism.
      Cimicifuga racemosa is not a phytoestrogen, has partial serotonin agonist action
      and has a modest effect on VMS. CONCLUSIONS: There are safe non-hormonal
      conventional treatments for menopausal VMS, although they are less efficacious
      than estrogens. The indication of phytochemicals is for women who make this
      choice on personal beliefs; long-term studies of larger groups of patients are
      needed to assess safety.

PMID- 22148910
TI  - Administration of a specific inhibitor of neutrophil elastase attenuates
      pulmonary fibrosis after acute lung injury in mice.
AB  - Excess production of neutrophil elastase contributes to the pathogenesis of acute
      lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the
      role of neutrophil elastase in the repair process following ALI/ARDS is not well
      understood. The objective of this study was to evaluate the effect of neutrophil
      elastase on the process of tissue repair after acute lung injury in mice. C57BL/6
      mice were exposed to sublethal irradiation followed by intranasal instillation of
      lipopolysaccharide (LPS) to generate a model of impaired lung repair. The authors
      assessed the histopathology, lung mechanics, and total lung collagen content 7
      days after irradiation and/or LPS-induced injury with daily administration of a
      neutrophil elastase inhibitor. The number of inflammatory cells in the
      bronchoalveolar lavage fluid (BALF) was also evaluated. In addition, the
      concentration of activated transforming growth factor (TGF)-beta1 in the BALF and
      the expression of phospho-SMAD2/3 were investigated. Irradiated and LPS-treated
      mice developed pulmonary fibrosis after injury. The neutrophil elastase inhibitor
      significantly decreased the collagen deposition in lung parenchyma and improved
      the static lung compliance of injured lungs. Administration of the neutrophil
      elastase inhibitor also decreased the accumulation of neutrophils in the BALF,
      TGF-beta1 activation, and expression of phospho-SMAD2/3. The authors conclude
      that inhibiting neutrophil elastase protects against the development of lung
      fibrosis after acute injury. In addition, these data suggest that this neutrophil
      elastase inhibitor has therapeutic potential for the fibroproliferative phase of
      ALI/ARDS.

PMID- 22148911
TI  - AlMe(3)-promoted formation of amides from acids and amines.
AB  - In the presence of AlMe(3), amines can be directly coupled with acids through
      dimethylaluminum amide intermediates to form the corresponding amides. A wide
      range of amines and acids including less nucleophilic amines, bulky amines,
      unprotected secondary amino acids, and acids with poor solubility were coupled
      smoothly to give the desired products in 55-98% yields.

PMID- 22148912
TI  - Quantifying the coverage density of poly(ethylene glycol) chains on the surface
      of gold nanostructures.
AB  - The coverage density of poly(ethylene glycol) (PEG) is a key parameter in
      determining the efficiency of PEGylation, a process pivotal to in vivo delivery
      and targeting of nanomaterials. Here we report four complementary methods for
      quantifying the coverage density of PEG chains on various types of Au
      nanostructures by using a model system based on HS-PEG-NH(2) with different
      molecular weights. Specifically, the methods involve reactions with fluorescamine
      and ninhydrin, as well as labeling with fluorescein isothiocyanate (FITC) and
      Cu(2+) ions. The first two methods use conventional amine assays to measure the
      number of unreacted HS-PEG-NH(2) molecules left behind in the solution after
      incubation with the Au nanostructures. The other two methods involve coupling
      between the terminal -NH(2) groups of adsorbed -S-PEG-NH(2) chains and FITC or a
      ligand for Cu(2+) ion, and thus pertain to the "active" -NH(2) groups on the
      surface of a Au nanostructure. We found that the coverage density decreased as
      the length of PEG chains increased. A stronger binding affinity of the initial
      capping ligand to the Au surface tended to reduce the PEGylation efficiency by
      slowing down the ligand exchange process. For the Au nanostructures and capping
      ligands we have tested, the PEGylation efficiency decreased in the order of
      citrate-capped nanoparticles > PVP-capped nanocages ~ CTAC-capped nanoparticles ?
      CTAB-capped nanorods, where PVP, CTAC, and CTAB stand for poly(vinyl
      pyrrolidone), cetyltrimethylammonium chloride, and cetyltrimethylammonium
      bromide, respectively.

PMID- 22148913
TI  - An unconventional route to high-efficiency dye-sensitized solar cells via
      embedding graphitic thin films into TiO2 nanoparticle photoanode.
AB  - Graphitic thin films embedded with highly dispersed titanium dioxide (TiO(2))
      nanoparticles were incorporated for the first time into the conventional dye
      sensitized solar cells (DSSCs), resulting in a remarkably improved cell
      efficiency due to its superior electron conductivity. Massively ordered arrays of
      TiO(2) dots embedded in carbon matrix were fabricated via UV-stabilization of
      polystyrene-block-poly(4-vinylpyridine) films containing TiO(2) precursors
      followed by direct carbonization. For dye-sensitized TiO(2) based solar cells
      containing carbon/TiO(2) thin layers at both sides of pristine TiO(2) layer, an
      increase of 62.3% [corrected] in overall power conversion efficiency was achieved
      compared with neat TiO(2)-based DSSCs. Such a remarkably improved cell efficiency
      was ascribed to the superior electron conductivity and extended electron lifetime
      elucidated by cyclic voltammetry and impedance spectroscopy.

PMID- 22148914
TI  - Gender-related association of AGT gene variants (M235T and T174M) with essential
      hypertension--a case-control study.
AB  - INTRODUCTION: The human angiotensinogen (AGT) is a promising candidate gene for
      evaluating susceptibility to essential hypertension (EH). We aimed to assess the
      association of the variants of AGT gene and the extent of risk involved in
      developing EH. METHODS: A case-control study was designed to compare 279
      hypertensive patients with 200 normotensive subjects. The frequency distribution
      of M235T and T174M polymorphisms of AGT gene was assessed by polymerase chain
      reaction (PCR)-restriction fragment length polymorphism (RFLP) method. A
      haplotype analysis was done to determine the risk conferred by the combination of
      alleles of the two polymorphisms for EH. RESULTS: The genotype distribution of
      the T174M variant differed significantly between hypertensives and normotensives,
      whereas genotypes of M235T variant did not show such difference. For M235T, MM
      genotype conferred an increase in risk for hypertension in women (odds ratios
      (OR) = 2.82; 95% confidence interval (CI) = 1.22-6.49). For the variant T174M,
      the TM genotype frequency was elevated in hypertensive females (36.5%) as
      compared to controls (18.8 %; P = .034). The 174M allele was more prevalent among
      female hypertensives than among female controls (0.20 vs. 0.12; P = .059). The
      haplotype analysis showed a significant association for the haplotypes of paired
      markers (M235 and 174M) with a chi(2) value of 8.037 (P = .045). CONCLUSION: Our
      findings suggest that the polymorphic variants of AGT gene-M235T and T174M-show
      association with hypertension.

PMID- 22148915
TI  - Distinct urinary metabolic profile of human colorectal cancer.
AB  - A full spectrum of metabolic aberrations that are directly linked to colorectal
      cancer (CRC) at early curable stages is critical for developing and deploying
      molecular diagnostic and therapeutic approaches that will significantly improve
      patient survival. We have recently reported a urinary metabonomic profiling study
      on CRC subjects (n = 60) and health controls (n = 63), in which a panel of
      urinary metabolite markers was identified. Here, we report a second urinary
      metabonomic study on a larger cohort of CRC (n = 101) and healthy subjects (n =
      103), using gas chromatography time-of-flight mass spectrometry and ultra
      performance liquid chromatography quadrupole time-of-flight mass spectrometry.
      Consistent with our previous findings, we observed a number of dysregulated
      metabolic pathways, such as glycolysis, TCA cycle, urea cycle, pyrimidine
      metabolism, tryptophan metabolism, polyamine metabolism, as well as gut microbial
      host co-metabolism in CRC subjects. Our findings confirm distinct urinary
      metabolic footprints of CRC patients characterized by altered levels of
      metabolites derived from gut microbial-host co-metabolism. A panel of metabolite
      markers composed of citrate, hippurate, p-cresol, 2-aminobutyrate, myristate,
      putrescine, and kynurenate was selected, which was able to discriminate CRC
      subjects from their healthy counterparts. A receiver operating characteristic
      curve (ROC) analysis of these markers resulted in an area under the receiver
      operating characteristic curve (AUC) of 0.993 and 0.998 for the training set and
      the testing set, respectively. These potential metabolite markers provide a novel
      and promising molecular diagnostic approach for the early detection of CRC.

PMID- 22148916
TI  - Dynamics of Zn(II) binding as a key feature in the formation of amyloid fibrils
      by Abeta11-28.
AB  - Supramolecular assembly of peptides and proteins into amyloid fibrils is of
      multifold interest, going from materials science to physiopathology. The binding
      of metal ions to amyloidogenic peptides is associated with several amyloid
      diseases, and amyloids with incorporated metal ions are of interest in
      nanotechnology. Understanding the mechanisms of amyloid formation and the role of
      metal ions can improve strategies toward the prevention of this process and
      enable potential applications in nanotechnology. Here, studies on Zn(II) binding
      to the amyloidogenic peptide Abeta11-28 are reported. Zn(II) modulates the
      Abeta11-28 aggregation, in terms of kinetics and fibril structures. Structural
      studies suggest that Abeta11-28 binds Zn(II) by amino acid residues Glu11 and
      His14 and that Zn(II) is rapidly exchanged between peptides. Structural and
      aggregation data indicate that Zn(II) binding induces the formation of the
      dimeric Zn(II)(1)(Abeta11-28)(2) species, which is the building block of
      fibrillar aggregates and explains why Zn(II) binding accelerates Abeta11-28
      aggregation. Moreover, transient Zn(II) binding, even briefly, was enough to
      promote fibril formation, but the final structure resembled that of apo-Abeta11
      28 amyloids. Also, seeding experiments, i.e., the addition of fibrillar
      Zn(II)(1)(Abeta11-28)(2) to the apo-Abeta11-28 peptide, induced aggregation but
      not propagation of the Zn(II)(1)(Abeta11-28)(2)-type fibrils. This can be
      explained by the dynamic Zn(II) binding between soluble and aggregated Abeta11
      28. As a consequence, dynamic Zn(II) binding has a strong impact on the
      aggregation behavior of the Abeta11-28 peptide and might be a relevant and so far
      little regarded parameter in other systems of metal ions and amyloidogenic
      peptides.

PMID- 22148917
TI  - Post-natal molecular adaptations in anteromedial and posterolateral bundles of
      the ovine anterior cruciate ligament: one structure with two parts or two
      distinct ligaments?
AB  - The human anterior cruciate ligament (ACL) is a composite structure of two
      anatomically distinct bundles: an anteromedial (AM) and posterolateral (PL)
      bundles. Tendons are often used as autografts for surgical reconstruction of ACL
      following severe injury. However, despite successful surgical reconstruction,
      some people experience re-rupture and later development of osteoarthritis.
      Understanding the structure and molecular makeup of normal ACL is essential for
      its optimal replacement. Reportedly the two bundles display different tensions
      throughout joint motion and may be fundamentally different. This study assessed
      the similarities and differences in ultrastructure and molecular composition of
      the AM and PL bundles to test the hypothesis that the two bundles of the ACL
      develop unique characteristics with maturation. ACLs from nine mature and six
      immature sheep were compared. The bundles were examined for mRNA and protein
      levels of collagen types I, III, V, and VI, and two proteoglycans. The fibril
      diameter composition of the two bundles was examined with transmission electron
      microscopy. Maturation does alter the molecular and structural composition of the
      two bundles of ACL. Although the PL band appears to mature slower than the AM
      band, no significant differences were detected between the bundles in the mature
      animals. We thus reject our hypothesis that the two ACL bundles are distinct. The
      two anatomically distinct bundles of the sheep ACL can be considered as two parts
      of one structure at maturity and material that would result in a structure of
      similar functionality can be used to replace each ACL bundle in the sheep.

PMID- 22148918
TI  - Workfunction-tunable, N-doped reduced graphene transparent electrodes for high
      performance polymer light-emitting diodes.
AB  - Graphene is a promising candidate to complement brittle and expensive transparent
      conducting oxides. Nevertheless, previous research efforts have paid little
      attention to reduced graphene, which can be of great benefit due to low-cost
      solution processing without substrate transfer. Here we demonstrate workfunction
      tunable, highly conductive, N-doped reduced graphene film, which is obtainable
      from the spin-casting of graphene oxide dispersion and can be successfully
      employed as a transparent cathode for high-performance polymer light-emitting
      diodes (PLEDs) as an alternative to fluorine-doped tin oxide (FTO). The sheet
      resistance of N-doped reduced graphene attained 300 Omega/? at 80% transmittance,
      one of the lowest values ever reported from the reduction of graphene oxide
      films. The optimal doping of quaternary nitrogen and the effective removal of
      oxygen functionalities via sequential hydrazine treatment and thermal reduction
      accomplished the low resistance. The PLEDs employing N-doped reduced graphene
      cathodes exhibited a maximum electroluminescence efficiency higher than those of
      FTO-based devices (4.0 cd/A for FTO and 7.0 cd/A for N-doped graphene at 17,000
      cd/m(2)). The reduced barrier for electron injection from a workfunction-tunable,
      N-doped reduced graphene cathode offered this remarkable device performance.

PMID- 22148919
TI  - Hoffmann reflex is increased after 14 days of daily repeated Achilles tendon
      vibration for the soleus but not for the gastrocnemii muscles.
AB  - In a previous study, Achilles tendon vibrations were enough to improve the
      triceps surae (TS) activation capacities and also to slightly increase TS
      Hoffmann reflex (H-reflex) obtained by summing up soleus (Sol) and gastrocnemii
      (GM and GL) EMGs. The purpose of the present study was to analyze separately Sol
      and GM or GL reflexes to account for different effects of the vibrations on the
      reflex excitability of the slow soleus and of the gastrocnemii muscles. A control
      group (n = 13) and a vibration group (n = 16) were tested in pre-test and post
      test conditions. The Achilles tendon vibration program consisted of 1 h of daily
      vibration (frequency: 50 Hz) applied during 14 days. Maximal Sol, GM and GL H
      reflexes, and M-waves were recorded, and their H(max)/M(max) ratios gave the
      index of reflex excitability. After the vibration protocol, only Sol
      H(max)/M(max) was enhanced (p < 0.001). The enhanced Sol reflex excitability
      after vibration is in favor of a decrease in the pre-synaptic inhibition due to
      the repeated vibrations and the high solicitation of the reflex pathway. Those
      results of a short period of vibration applied at rest may be limited to the
      soleus because of its high density in muscle spindles and slow motor units, both
      structures being very sensitive to vibrations.

PMID- 22148920
TI  - Effect of temperature and aging time on the rheological behavior of aqueous
      poly(ethylene glycol)/Laponite RD dispersions.
AB  - The viscoelastic properties of 2% poly(ethylene glycol) aqueous solutions
      containing Laponite RD from 1% to 4% were investigated by oscillatory and flow
      measurements in the temperature range of 15-40  degrees C. The enhancement of the
      clay content from mixture causes the increase of the viscoelastic moduli and the
      change of the flow from liquid-like behavior (Maxwellian fluid) to a solid-like
      one at a set temperature. The longest relaxation times (tau(1)) of the mixtures
      with low clay concentrations (1% and 2%) are not affected by changes in
      temperature unlike the samples having high content of clay at which tau(1)
      increases above 30  degrees C and below 17.5  degrees C. The characteristic
      behavior of the mixtures with the high clay concentration could be explained by
      considering the effect of Brownian motion on the network structure formed in
      these dispersions as well as by the poor solubility of poly(ethylene glycol) in
      water at high temperatures. The flow activation energy was determined and
      discussed. An abrupt increase of the flow activation energy was evidenced between
      2% and 3% Laponite RD. The rheological measurements carried out at different rest
      times showed a decrease of the gelation time from 1 week to 2 h when the clay
      concentration increases from 2% to 4%. The aging kinetics of poly(ethylene
      glycol)/Laponite RD/water mixtures, investigated at 25  degrees C, revealed the
      increase of the viscosity-rate kinetic constant by increasing the clay
      concentration.

PMID- 22148921
TI  - Synthesis and biological profile of the pan-vascular endothelial growth factor
      receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like
      homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2
      methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one
      (CEP-11981): a novel oncology therapeutic agent.
AB  - A substantial body of evidence supports the utility of antiangiogenesis
      inhibitors as a strategy to block or attenuate tumor-induced angiogenesis and
      inhibition of primary and metastatic tumor growth in a variety of solid and
      hematopoietic tumors. Given the requirement of tumors for different cytokine and
      growth factors at distinct stages of their growth and dissemination, optimal
      antiangiogenic therapy necessitates inhibition of multiple, complementary, and
      nonredundant angiogenic targets. 11-(2-Methylpropyl)-12,13-dihydro-2-methyl-8
      (pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (11b, CEP
      11981) is a potent orally active inhibitor of multiple targets (TIE-2, VEGF-R1,
      2, and 3, and FGF-R1) having essential and nonredundant roles in tumor
      angiogenesis and vascular maintenance. Outlined in this article are the design
      strategy, synthesis, and biochemical and pharmacological profile for 11b, which
      completed Phase I clinical assessing safety and pharmacokinetics allowing for the
      initiation of proof of concept studies.

PMID- 22148922
TI  - Thymus peptides regulate activity of RAW 264.7 macrophage cells: inhibitory
      analysis and a role of signal cascades.
AB  - OBJECTIVES: The aim of this study was to reveal T-lymphocyte-independent
      mechanisms of thymic peptide-mediated immunomodulation. METHODS: The effects of
      two thymic peptides- thymulin and thymopentin were studied in cultured RAW 264.7
      macrophages (lipopolysaccharide-stimulated or unstimulated) by measuring cytokine
      production and signal protein levels. RESULTS: Both peptides increased
      proinflammatory cytokine secretion by unstimulated RAW 264.7 macrophages and
      these effects were blocked by the NF-kappaB cascade inhibitor, stress-activated
      protein kinase (SAPK)/JNK cascade inhibitor and, to a lesser extent, Toll-like 4
      receptor activity inhibitor. In macrophages stimulated by bacterial
      lipopolysaccharide, peptides alone did not affect cytokine secretion, but
      significantly enhanced effects of each of the inhibitors. Thymopentin increased
      activation of both NF-kappaB and SAPK/JNK cascades in unstimulated macrophages,
      while thymulin significantly decreased activation of the SAPK/JNK but not NF
      kappaB cascade in LPS-stimulated macrophages. Thymulin and thymopentin increased
      production of the heat shock protein HSP72 both in LPS-stimulated and
      unstimulated cells. CONCLUSIONS: Thymulin and thymopentin are effective anti
      inflammatory modulators with direct actions on innate immune cells; the effects
      involve multiple signal cascades, including NF-kappaB and SAPK/JNK pathways.
      Since signaling cascades are now considered to be targets for new therapies,
      thymic peptides may be prospective modulators of signaling cascades, acting alone
      or in combination with other agents.

PMID- 22148923
TI  - Direct visualization of bactericidal action of cationic conjugated
      polyelectrolytes and oligomers.
AB  - The bactericidal mechanisms of poly(phenylene ethynylene) (PPE)-based cationic
      conjugated polyelectrolytes (CPE) and oligo-phenylene ethynylenes (OPE) were
      investigated using electron/optical microscopy and small-angle X-ray scattering
      (SAXS). The ultrastructural analysis shows that polymeric PPE-Th can
      significantly remodel the bacterial outer membrane and/or the peptidoglycan
      layer, followed by the possible collapse of the bacterial cytoplasm membrane. In
      contrast, oligomeric end-only OPE (EO-OPE) possesses potent bacteriolysis
      activity, which efficiently disintegrates the bacterial cytoplasm membrane and
      induces the release of bacterial cell content. Using single giant vesicles and
      SAXS, we demonstrated that the membrane perturbation mechanism of EO-OPE against
      model bacterial membranes results from a 3D membrane phase transition or
      perturbation.

PMID- 22148924
TI  - Analysis of wind velocity and release angle effects on discus throw using
      computational fluid dynamics.
AB  - The aim of this paper is to study the aerodynamics of discus throw. A comparison
      of numerical and experimental performance of discus throw with and without
      rotation was carried out using the analysis of lift and drag coefficients.
      Initial velocity corresponding to variation angle of around 35.5 degrees  was
      simulated. Boundary condition, on the top and bottom boundary edges of
      computational domain, was imposed in order to eliminate external influences on
      the discus; a wind resistance was calculated for the velocity values of 25 and 27
      m/s. The results indicate that the flight distance (D) was strongly affected by
      the drag coefficient, the initial velocity, the release angle and the direction
      of wind velocity. It was observed that these variables change as a function of
      discus rotation. In this study, results indicate a good agreement of D between
      experimental values and numerical results.

PMID- 22148925
TI  - Click dendrimers and triazole-related aspects: catalysts, mechanism, synthesis,
      and functions. A bridge between dendritic architectures and nanomaterials.
AB  - One of the primary recent improvements in molecular chemistry is the now decade
      old concept of click chemistry. Typically performed as copper-catalyzed azide
      alkyne (CuAAC) Huisgen-type 1,3-cycloadditions, this reaction has many
      applications in biomedicine and materials science. The application of this
      chemistry in dendrimer synthesis beyond the zeroth generation and in nanoparticle
      functionalization requires stoichiometric use of the most common click catalyst,
      CuSO(4).5H(2)O with sodium ascorbate.  Efforts to develop milder reaction
      conditions for these substrates have led to the design of polydentate nitrogen
      ligands. Along these lines, we have described a new, efficient, practical, and
      easy-to-synthesize catalytic complex, [Cu(I)(hexabenzyltren)]Br, 1 [tren = tris(2
      aminoethyl)amine], for the synthesis of relatively large dendrimers and
      functional gold nanoparticles (AuNPs). This efficient catalyst can be used alone
      in 0.1% mol amounts for nondendritic click reactions or with the sodium-ascorbate
      additive, which inhibits aerobic catalyst oxidation. Alternatively, catalytic
      quantities of the air-stable compounds hexabenzyltren and CuBr added to the click
      reaction medium can provide analogously satisfactory results. Based on this
      catalyst as a core, we have also designed and synthesized analogous Cu(I)
      centered dendritic catalysts that are much less air-sensitive than 1 and are
      soluble in organic solvents or in water (depending on the nature of the terminal
      groups). These multivalent catalysts facilitate efficient click chemistry and
      exert positive dendritic effects that mimic enzyme activity. We propose a
      monometallic CuAAC click mechanism for this process.  Although the primary use of
      click chemistry with dendrimers has been to decorate dendrimers with a large
      number of molecules for medicinal or materials purposes, we are specifically
      interested in the formation of intradendritic [1,2,3]-triazole heterocycles that
      coordinate to transition-metal ions via their nitrogen atoms. We describe
      applications including molecular recognition of anions and cations and the
      stabilization of transition metal nanoparticles according to a principle
      pioneered by Crooks with poly(amido amine) (PAMAM) dendrimers, and in particular,
      the control of structural and reactivity parameters in which the intradendritic
      [1,2,3]-triazoles and peripheral tripodal tri(ethylene glycol) termini play key
      roles in the click-dendrimer mediated synthesis and stabilization of gold
      nanoparticles (AuNPs). By varying these parameters, we have stabilized water
      soluble, weakly liganded AuNPs between 1.8 and 50 nm in size and have shown large
      differences in behavior between AuNPs and PdNPs. Overall, the new catalyst design
      and the possibilities of click dendrimer chemistry introduce a bridge between
      dendritic architectures and the world of nanomaterials for multiple applications.

PMID- 22148926
TI  - The longitudinal role of breastfeeding in mothers' and fathers' relationship
      quality trajectories.
AB  - BACKGROUND: Guided by a family systems perspective, this study investigated
      whether breastfeeding plays a role in the quality of the mother-father intimate
      relationship over the course of child development. METHODS: Using a prospective,
      longitudinal design, and data drawn from the National Institute of Child Health
      and Human Development Study of Early Child Care and Youth Development (n=986
      couples), the present study examined the predictive role of breastfeeding in the
      first 3 years of life (for up to 4 months and for 5 months or longer, relative to
      never breastfeeding) in maternal and paternal trajectories of intimate
      relationship quality. The outcome variable of interest was emotional intimacy,
      rated by mothers and fathers when children were 54 months of age, in grades 1, 3,
      5, and 6, and 15 years of age. RESULTS: Multivariate hierarchical linear
      modeling, which appropriately handled dyadic data and accounted for effects of
      demographic covariates and earlier relationship quality, indicated that
      breastfeeding uniquely predicted increases in mothers' (but not fathers') marital
      quality levels over time. There was no difference in the strength of the positive
      associations for shorter versus longer breastfeeding duration. The findings
      suggest that improved intimate relationship quality may be another psychosocial
      benefit experienced by breastfeeding mothers. CONCLUSION: The findings underscore
      the importance of considering breastfeeding in the context of intimate
      relationships and may be of interest to women weighing the decision to
      breastfeed, their partners, and healthcare providers.

PMID- 22148927
TI  - Breastfeeding following emergency peripartum hysterectomy.
AB  - Emergency peripartum hysterectomy (EPH) is usually performed in cases of
      intractable obstetric hemorrhage unresponsive to conservative treatment. EPH is
      associated with a high incidence of maternal morbidity and mortality. Most of
      these women do not have the opportunity to even start breastfeeding. We report a
      case where breastfeeding was attempted after EPH. The mother spent 6 days in the
      intensive care unit and suffered several medical and surgical complications. On
      day 7 she was reunited with her baby. One month later, a diagnosis of post
      traumatic stress disorder was made. Breastfeeding became very important, with the
      patient frequently expressing that this was the most healing aspect in her
      recovery from the traumatic EPH. At 3 months, five daily feeds were supplemented
      with formula. Breastfeeding, principally nocturnal, continued 6 months after
      childbirth, with the baby being weaned at 7 months. Women who undergo EPH need
      psychological support. The option of breastfeeding should be considered even days
      or weeks after the surgical intervention as it can be a healing experience for
      some women who are grieving the loss of their fertility. Professional specialized
      breastfeeding support should be offered in these cases, and the possibility of
      reuniting mother and infant even when the mother is in the intensive care unit
      should be considered.

PMID- 22148928
TI  - A mother with green breastmilk due to multivitamin and mineral intake: a case
      report.
AB  - It is a globally accepted fact that breastfeeding reduces infant mortality and
      morbidity, optimizes infant growth, is superior to other forms of nutrition for
      infants, and has economic advantages for the family and the country. This case
      study reports a new mother who stopped breastfeeding her baby because her
      breastmilk was green. When her second child was born, her milk came in green, and
      a consultation was requested from pediatrics and infectious diseases. A physical
      examination and laboratory tests revealed that the abnormal color of her
      breastmilk was related to multivitamin intake. The patient was advised to
      continue breastfeeding despite the odd color. Although clinical specialists know
      that the color of breastmilk can change with the ingestion of certain medications
      and foods, mothers are usually unaware and may unnecessarily terminate
      breastfeeding.

PMID- 22148929
TI  - Breastfeeding experiences among physicians.
AB  - BACKGROUND: During medical school and residency training, physicians are taught
      that breastfeeding is the preferred feeding for all infants, with rare
      exceptions. But evidence is accumulating that while physician mothers have a high
      rate of breastfeeding initiation, they face significant obstacles to sustained
      breastfeeding. METHODS: In our academic medical center, we conducted a brief
      survey of physicians who have young children, to explore their own experiences
      with breastfeeding. The survey explored the physician-as-parent's own experiences
      with breastfeeding -- prenatal intentions, postnatal difficulties, ability to
      meet goals, emotions if goals were not met, resources for support pre- and
      postnatally, and ideas about what would have helped her breastfeed longer.
      RESULTS: Two-thirds of the physicians who initiated breastfeeding had
      difficulties. Among those with difficulties, about three-fourths were able to
      resolve them. CONCLUSIONS: Even mothers who are medical professionals experience,
      and often cannot overcome, difficulties with breastfeeding. Women in medicine
      need enhanced breastfeeding support and services/resources. Advocacy is needed,
      in our work environments, for better breastfeeding support not only for our
      physician colleagues, but also for all lactating employees within our
      institutions.

PMID- 22148930
TI  - Tracking of fatness during childhood, adolescence and young adulthood: a 7-year
      follow-up study in Madeira Island, Portugal.
AB  - AIMS: Investigating tracking of fatness from childhood to adolescence, early
      adolescence to young adulthood and late adolescence to young adulthood. SUBJECTS
      AND METHODS: Participants from the Madeira Growth Study were followed during an
      average period of 7.2 years. Height, body mass, skin-folds and circumferences
      were measured, nine health- and performance-related tests were administered and
      the Baecke questionnaire was used to assess physical activity. Skeletal maturity
      was estimated using the TW3 method. RESULTS: The prevalence of overweight plus
      obesity ranged from 8.2-20.0% at baseline and from 20.4-40.0% at follow-up, in
      boys. Corresponding percentages for girls were 10.6-12.0% and 13.2-18.0%. Inter
      age correlations for fatness indicators ranged from 0.43-0.77. BMI, waist
      circumference and sum of skin-folds at 8, 12 and 16-years old were the main
      predictors of these variables at 15, 19 and 23-years old, respectively. Strength,
      muscular endurance and aerobic fitness were negatively related to body fatness.
      Physical activity and maturation were independently associated with adolescent
      (15 years) and young adult (19 years) fatness. CONCLUSIONS: Over 7.2 years,
      tracking was moderate-to-high for fatness. Variance was explained by fatness
      indicators and to a small extent by physical fitness, physical activity and
      maturation.

PMID- 22148931
TI  - Feasibility, criterion validity and retest reliability of exercise testing using
      the Astrand-rhyming test protocol with an adaptive ergometer in stroke patients.
AB  - PURPOSE: (i) to establish feasibility of the Astrand-Rhyming submaximal protocol
      using the adaptive ergometer in healthy participants, (ii) to test feasibility of
      this protocol in stroke patients, (iii) to identify clinical characteristics of
      stroke patients which limit testing, (iv) to establish criterion validity of
      V.O(2 steady state) ergometry data against the gold standard open-circuit
      spirometry measure and, lastly, (v) to test-retest reliability of the data
      generated by the test protocol. METHODS: A descriptive, cross sectional study
      design was implemented. Ten healthy participants (5 men, mean age 32 +/- 6.6 y)
      and 20 chronic stroke patients (14 men, mean age 61.0 +/- 11.6 y; mean months
      since stroke, 65.6 +/- 34.4 y) took part in this study. Independent t-tests, Mann
      Whitney U tests and chi-square test identified characteristics of those who
      failed to successfully complete the protocol. Interclass correlation coefficients
      (ICCs) tested criterion validity and test-retest reliability. RESULTS: No adverse
      events occurred. All healthy participants (100%) complied with the test protocol
      and estimation of V.O(2max). 90% of stroke patients completed the test, with
      V.O(2max) estimated in 35% (7 / 20) stroke patients. Age and beta-blocker
      medication demonstrated statistical significance as barriers to the test protocol
      at p = 0.04 and p = 0.03, respectively. Criterion validity established by
      comparison with breath-by-breath gas analysis was excellent (ICC 0.93). Retest
      reliability of V.O(2max), steady-state V.O(2) and oxygen pulse had ICCs of 0.94,
      0.96 and 0.97, respectively. CONCLUSIONS: The Astrand-Rhyming test protocol and
      MOTOmed Viva2 adaptive ergometer were feasible in healthy participants. The
      protocol was not feasible for V.O(2max) estimation for the majority of stroke
      patients based on heart rate response. The adapted steady state VO2 measures used
      however were feasible and had strong relationship to actual VO2 consumption.
      Criterion validity and retest reliability of test data were excellent.

PMID- 22148932
TI  - Effects of an intervention plan on nursing student success.
AB  - Student attrition from nursing programs due to academic failure negatively
      affects students, nursing programs, and the health care industry. The purpose of
      this retrospective study was to determine the success of an intervention plan for
      practical nursing (PN) and associate degree nursing (ADN) students who were at
      risk for failure in coursework compared with outcomes from years without the
      plan. Records of 384 students were accessed. A 6% decrease in involuntary
      withdrawal due to academic failure with the intervention plans was noted. Sixty
      four percent of the PN students and 86% of the ADN students with a plan completed
      the program. Ninety-six percent of the PN students and 84% of ADN students in
      intervention plans were successful on the NCLEX((r)) on the first attempt. A
      statistically significant difference (p < 0.001) between traditional and
      nontraditional students in program completion existed prior to the intervention,
      which was eliminated with implementation of the intervention plans.

PMID- 22148933
TI  - Action research as a strategy for teaching an undergraduate research course.
AB  - Action research is rarely, if ever, referred to in the textbooks used in
      undergraduate nursing programs. While redesigning a 2009-2010 research course for
      junior-level baccalaureate nursing students, the action research strategy was
      used to conduct a semester-long research project. After identifying a list of 15
      health risks on campus, students prioritized and came to consensus on the health
      problem to be targeted. Each week, students followed the steps of the research
      process as the related topic was covered in class. At the end of the semester,
      students presented their findings at the annual on-campus Student Research
      Conference. Students have since completed a total of three campus-wide research
      projects. The results of these projects have been incorporated as a required
      assignment in the senior-level Community Health Nursing course and are now being
      used to create health promotion materials for the campus e-magazine.

PMID- 22148934
TI  - Effects of mental illness on the family: experiential family assessment to
      promote students' affective learning.
AB  - Mental health nursing faculty are challenged to connect with students on an
      affective level in their courses. One important strategy to promote affective
      learning is to understand the experience of the family caregiver. There is
      relatively little student access to family caregivers of individuals who are
      identified as severely and persistently mentally ill. Consequently, nursing
      students may not appreciate the myriad psychosocial challenges and adaptations
      that family caregivers of these individuals are forced to make, often for a
      lifetime. This article describes a unique teaching strategy that promotes
      cognitive and affective learning while also providing students with a clear
      window into the dynamics of families of people with mental illness.

PMID- 22148935
TI  - Parent-nursing student communication practice: role-play and learning outcomes.
AB  - Parents accompanying their child's hospitalization can experience stress
      associated with the child's illness, treatments, and major alterations in family
      life. Nurses often serve as the primary communicator and cultural broker because
      of their constant presence at the child's bedside. Nursing students may not have
      essential parent-nurse communication competencies. In an innovative method of
      teaching nursing students about communicating with parents, 64 undergraduate
      nursing students participated in a parent-led postconference with a nursing
      instructor. The parents provided background and led role-play activities and
      debriefing sessions with students. Feedback provided by students before and after
      the parent session included requests for additional parents' experiences,
      appreciation and exceeded expectations of hands-on experience, recognized value
      of information provided, and the recommendation that all students attend. We
      demonstrate that empathy is a teachable skill, nursing students are apprehensive
      about communicating with parents, and nursing students do not understand how much
      families rely on nurses.

PMID- 22148936
TI  - Pressure and surface tension control self-assembled structures in mixtures of
      Pegylated and non-pegylated lipids.
AB  - PEGylated lipid membrane structure and phase behavior are important areas of
      study because of their potential in various biochemical, biomedical, and
      pharmaceutical applications. Here, we study mixed bilayers of DOPC (1,2-dioleoyl
      sn-glycero-3-phosphocholine) and PEGylated DOPCs (on phosphorus) in water using
      the MARTINI coarse-grained force field and show that the self-assembled
      structures can be changed between micelles and bilayers by applying different
      isotropic and semiisotropic (i.e., surface tension) pressure conditions. Radial
      distribution functions as well as radii of gyration confirm that structures are
      distinctly different. The results indicate that environmental conditions can be
      used to transform, manipulate, and eventually control lipid assemblies.

PMID- 22148937
TI  - Low Wilms' tumor gene expression in tumor tissues predicts poor prognosis in
      patients with non-small-cell lung cancer.
AB  - We elucidated the relationship between prognosis of non-small-cell lung cancer
      (NSCLC) and Wilms' tumor gene (WT1) mRNA expression in tumor tissue. The WT1 mRNA
      expression levels of the fatal cases were lower as compared with those of the
      survival cases. Overall survival (OS) and disease-free survival (DFS) of the high
      WT1 expression group were longer than of the low expression group. As for
      squamous cell lung cancer (SQLC), low WT1 expression was significantly associated
      with lymph node metastasis. Cox analysis revealed that the gene level was a
      significant prognostic factor in OS and DFS. Low WT1 expression predicted poor
      prognosis in patients with NSCLC.

PMID- 22148938
TI  - Emerging adenosine receptor agonists: an update.
AB  - Adenosine receptors (ARs), the major targets of caffeine and theophylline,
      comprise four receptor subtypes designated as A(1), A(2A), A(2B) and A(3). Over a
      dozen AR agonists are currently in clinical trials for various conditions,
      including cardiac arrhythmias, neuropathic pain, myocardial perfusion imaging,
      cardiac ischemia, inflammatory diseases and cancer. Adenosine (nonselective),
      regadenoson (A(2A)) and dipyridamole (act indirectly via ARs) have received
      regulatory approval for clinical use. The present editorial will give a brief
      update on the current status of AR agonists in clinical trials.

PMID- 22148939
TI  - Pd-catalyzed olefination of perfluoroarenes with allyl esters.
AB  - An efficient Pd(II)-catalyzed direct olefination of perfluoroarenes with allyl
      esters is demonstrated. Under the typical conditions, the coupling reaction of
      fluorinated-arenes with allylic esters proceeded via a beta-H elimination rather
      than a beta-OAc elimination to give the corresponding gamma-substituted allylic
      esters.

PMID- 22148940
TI  - Identifying assessment measures and interventions reported for Thai children with
      cerebral palsy using the ICF-CY framework.
AB  - BACKGROUND: Cerebral palsy (CP) is the most common disability in childhood. The
      International Classification of Functioning, Disability and Health (ICF) provides
      a standard framework for classifying performance in people with disability,
      including children with CP. Linking measures actually reported with the ICF
      classification promotes best practice, especially pertinent in developing
      countries such as Thailand. This study aimed to explore the charted demographic
      data, assessment and intervention measures reported for children with CP in
      Central region of Thailand using the ICF for children and youths (ICF-CY)
      framework to clarify the scope of actual management practice in this population.
      METHODS: Charts of children admitted to four public hospitals and two schools in
      2007-2009 were age stratified, and approximately 48% audited (n = 269). RESULTS:
      Contextual information was clearly reported, and measures could be classified
      across all components of the ICF, being mainly classified in Body Structures and
      Functions and to a lesser degree, in Activities and Participation. Our ability to
      compare across cultures was affected by poor recording practices limiting the
      amount and quality of data available. CONCLUSIONS: Classifying measures of
      children with CP in Thailand in terms of the ICF-CY framework demonstrates their
      holistic management as well as where gaps need to be addressed, and thus
      contributes to best practice.

PMID- 22148941
TI  - Porphyrin-silicon hybrid field-effect transistor with individually addressable
      top-gate structure.
AB  - A conductance-controllable hybrid device that utilizes the photoinduced charge
      transfer behavior of a porphyrin in a field-effect transistor (FET) with a
      nanogap is proposed and analyzed. A conventional metal-oxide-semiconductor (MOS)
      structure is modified to form a nanogap in which the porphyrin can be embedded.
      The conductance of an inversion channel is controlled by the negatively charged,
      optically activated porphyrin molecules. The proposed nanogap-formed MOSFET
      structure solves the conventional dilemma that a top-gate cannot be used for an
      organic-inorganic hybrid device because the top-gate blocks an entire area of a
      channel where organic material should be immobilized. The top-gate structure has
      much practicality compared with the back-gate structure because each device can
      be controlled individually. Furthermore, the device is highly compatible with the
      chip-based integrated system because the fabrication process follows the standard
      complementary metal-oxide-semiconductor (CMOS) technology. The charge transfer
      mechanisms between silicon and porphyrin are analyzed using devices with
      different doping polarities and geometrical parameters. The results show that the
      influence of the negative charge of the porphyrin in the device is reversed when
      opposite doping polarities are used. The device characteristics can be
      comprehensively evaluated using the energy band diagram analysis and simulation.
      The possible application of the proposed device for nonvolatile memory is
      demonstrated using the optical charging and electrical discharging behavior of
      the porphyrins.

PMID- 22148942
TI  - The influence of perceptions of HIV infection, care, and identity on care entry.
AB  - The benefits of accessing HIV care after diagnosis (e.g., improved clinical
      outcomes and reduced transmission) are well established. However, many persons
      who are aware that they are HIV infected have never received HIV medical care.
      During 2008-2010, we conducted 43 in-depth interviews in three health department
      jurisdictions among adults who had received an HIV diagnosis but who had never
      accessed HIV medical care. Respondents were selected from the HIV/AIDS Reporting
      System, a population-based surveillance system. We explored how respondents
      perceived HIV infection and HIV medical care. Most respondents associated HIV
      with death. Many respondents said that HIV medical care was not necessary until
      one is sick. Further, we explored how these perceptions may have conflicted with
      one's identity and thus served as barriers to timely care entry. Most respondents
      perceived themselves as healthy. All respondents acknowledged their HIV
      serostatus, but many did not self-identify as HIV-positive. Several respondents
      expressed that they were not ready to receive HIV care immediately but felt that
      they would eventually attempt to access care. Some stated that they needed time
      to accept their HIV diagnosis before entering care. To improve timely linkage to
      care, we suggest that during the posttest counseling session and subsequent
      linkage-to-care activities, counselors and service providers discuss patient
      perceptions of HIV, particularly to address beliefs that HIV infection is a
      "death sentence" or that HIV care is necessary only for those who exhibit
      symptoms.

PMID- 22148943
TI  - Electroencephalogram and heart rate measures of working memory at 5 and 10 months
      of age.
AB  - We recorded electroencephalogram (EEG; 6-9 Hz) and heart rate (HR) from infants
      at 5 and 10 months of age during baseline and performance on the looking A-not-B
      task of infant working memory (WM). Longitudinal baseline-to-task comparisons
      revealed WM-related increases in EEG power (all electrodes) and EEG coherence
      (medial frontal-occipital electrode pairs) at both ages. WM-related decreases in
      HR were only present at 5 months, and WM-related increases in EEG coherence
      became more localized by 10 months. Regression analyses revealed that baseline-to
      task changes in psychophysiology accounted for variability in WM performance at
      10 but not 5 months. HR and EEG power (medial frontal and lateral frontal
      electrodes) were unique predictors of variability in 10-month WM performance.
      These findings are discussed in relation to frontal lobe development and
      represent the first comprehensive longitudinal analysis of age-related changes in
      the behavioral and psychophysiological correlates of WM.

PMID- 22148944
TI  - Sex differences during visual scanning of occlusion events in infants.
AB  - A growing number of sex differences in infancy have been reported. One task on
      which they have been observed reliably is the event-mapping task. In event
      mapping, infants view an occlusion event involving 1 or 2 objects, the occluder
      is removed, and then infants see 1 object. Typically, boys are more likely than
      girls to detect an inconsistency between a 2-object occlusion event and a 1
      object display. The current research investigated underlying reasons for this sex
      difference. Three eye-tracking experiments were conducted with infants at 9 and 4
      months (mean age). Infants saw a ball-box or ball-ball occlusion event followed
      by a 1-ball display; visual scanning of the occlusion event and the 1-ball
      display was recorded. Older boys were more likely than older girls to visually
      track the objects through occlusion and more likely to detect an inconsistency
      between the ball-box event and the 1-ball display. In addition, tracking objects
      through occlusion was related to infants' scanning of the 1-ball display. Both
      younger boys and girls failed to track the objects through occlusion and to
      detect an inconsistency between the ball-box event and the 1-ball display. These
      results suggest that infants' capacity to track objects through occlusion
      facilitates extraction of the structure of the initial event (i.e., the number of
      distinct objects involved) that infants can map onto the final display and that
      sex differences in the capacity emerge between 4 and 9 months. Possible
      explanations for how the structure of an occlusion event is extracted and mapped
      are considered.

PMID- 22148945
TI  - Exergaming immediately enhances children's executive function.
AB  - The current study examined an important aspect of experience--physical activity-
      that may contribute to children's executive function. The design attempted to
      tease apart 2 important aspects of children's exercise by examining the separate
      and combined effects of acute physical activity and cognitive engagement on an
      aspect of children's executive functioning. In a 2 * 2 within-subject
      experimental design, children (N = 33, 6 to 10 years old) completed activities
      that varied systematically in both physical activity (physically active video
      games versus sedentary video activities) and cognitive engagement (challenging
      and interactive video games versus repetitive video activities). Cognitive
      functioning, including executive function, was assessed after each activity by a
      modified flanker task (Rueda et al., 2004). Whereas cognitive engagement had no
      effect on any aspect of task performance, physical activity (i.e., exergaming)
      enhanced children's speed to resolve interference from conflicting visuospatial
      stimuli. Age comparisons indicated improvements with age in the accuracy of
      resolving interference and in overall response time. The results extend past
      research by showing more precisely how physical activity influences executive
      function and how this effect differs from the improvements that occur with
      development.

PMID- 22148946
TI  - Approach-withdrawal and the role of the striatum in the temperament of behavioral
      inhibition.
AB  - Behavioral inhibition is a temperament characterized in infancy and early
      childhood by a tendency to withdraw from novel or unfamiliar stimuli. Children
      exhibiting this disposition, relative to children with other dispositions, are
      more socially reticent, less likely to initiate interaction with peers, and more
      likely to develop anxiety over time. Until recently, a dominant model attributed
      this disposition to reductions in the threshold for engaging the circuitry
      supporting fear learning, particularly the amygdala. Recent work, however, also
      has implicated striatal circuitry and other regions that constitute components of
      a presumed reward system. A series of studies found that behaviorally inhibited
      adolescents display heightened activation of striatal structures to cues
      indicating an opportunity to receive reward. This article reviews evidence
      implicating dual roles for fear and reward circuitry in the expression of
      behavioral inhibition.

PMID- 22148948
TI  - Preschoolers are able to take merit into account when distributing goods.
AB  - Classic studies in developmental psychology demonstrate a relatively late
      development of equity, with children as old as 6 or even 8-10 years failing to
      follow the logic of merit--that is, giving more to those who contributed more.
      Following Piaget (1932), these studies have been taken to indicate that judgments
      of justice develop slowly and follow a stagelike progression, starting off with
      simple rules (e.g., equality: everyone receives the same) and only later on in
      development evolving into more complex ones (e.g., equity: distributions match
      contributions). Here, we report 2 experiments with 3- and 4-year-old children (N
      = 195) that contradict this constructivist account. Our results demonstrate that
      children as young as 3 years old are able to take merit into account by
      distributing tokens according to individual contributions but that this ability
      may be hidden by a preference for equality.

PMID- 22148947
TI  - Adaptive patterns of stress responsivity: a preliminary investigation.
AB  - The adaptive calibration model (ACM) is an evolutionary-developmental theory of
      individual differences in stress responsivity. In this article, we tested some
      key predictions of the ACM in a middle childhood sample (N = 256). Measures of
      autonomic nervous system activity across the sympathetic and parasympathetic
      branches validated the 4-pattern taxonomy of the ACM via finite mixture modeling.
      Moreover, the 4 patterns of responsivity showed the predicted associations with
      family stress levels but no association with measures of ecological stress. Our
      hypotheses concerning sex differences in responsivity were only partly confirmed.
      This preliminary study provides initial support for the key predictions of the
      ACM and highlights some of the methodological challenges that will need to be
      considered in future research on this topic.

PMID- 22148949
TI  - Uranium pyrrolylamine complexes featuring a trigonal binding pocket and
      interligand noncovalent interactions.
AB  - The syntheses of tri- and tetravalent uranium complexes of the Ar(F)(3)TPA(3-)
      ligand [Ar(F) = 3,5-bis(trifluoromethyl)phenyl; TPA = tris(pyrrolyl-alpha
      methylamine)] are described. Interligand noncovalent interactions between arene
      groups within the complexes are detected both in the solid state and in solution.

PMID- 22148950
TI  - Comparison of carrier multiplication yields in PbS and PbSe nanocrystals: the
      role of competing energy-loss processes.
AB  - Infrared band gap semiconductor nanocrystals are promising materials for
      exploring generation III photovoltaic concepts that rely on carrier
      multiplication or multiple exciton generation, the process in which a single high
      energy photon generates more than one electron-hole pair. In this work, we
      present measurements of carrier multiplication yields and biexciton lifetimes for
      a large selection of PbS nanocrystals and compare these results to the well
      studied PbSe nanocrystals. The similar bulk properties of PbS and PbSe make this
      an important comparison for discerning the pertinent properties that determine
      efficient carrier multiplication. We observe that PbS and PbSe have very similar
      biexciton lifetimes as a function of confinement energy. Together with the
      similar bulk properties, this suggests that the rates of multiexciton generation,
      which is the inverse of Auger recombination, are also similar. The carrier
      multiplication yields in PbS nanocrystals, however, are strikingly lower than
      those observed for PbSe nanocrystals. We suggest that this implies the rate of
      competing processes, such as phonon emission, is higher in PbS nanocrystals than
      in PbSe nanocrystals. Indeed, our estimations for phonon emission mediated by the
      polar Frohlich-type interaction indicate that the corresponding energy-loss rate
      is approximately twice as large in PbS than in PbSe.

PMID- 22148951
TI  - A benzo-21-crown-7/secondary ammonium salt [c2]daisy chain.
AB  - A [c2]daisy chain has been constructed from a heteroditopic monomer based on the
      benzo-21-crown-7/secondary ammonium salt recognition motif as shown by single
      crystal X-ray analysis. It has been further demonstrated that the complexation
      behavior of this heteroditopic monomer in solution can be controlled by changing
      the solution pH or adding/removing K(+).

PMID- 22148952
TI  - Advances in the design and synthesis of prazosin derivatives over the last ten
      years.
AB  - INTRODUCTION: Mechanistic, translational and pharmacological studies led to the
      identification and discovery of the preferred localization, binding
      characteristics, structure and functional properties of alpha1-adrenoceptor
      (alpha1-AR) subtypes in the bladder neck, bladder and prostate gland. The
      evidence gathered on alpha1-ARs, provided a molecular platform for the
      development of subtype-selective antagonists, resulting in more effective
      approaches targeting those receptors for the treatment of outlet bladder
      obstruction and benign prostate hyperplasia. AREAS COVERED: Advances over the
      last decade in the design and optimization of Prazosin, Doxazosin and Terazosin
      quinazoline-based derivatives as alpha1-AR antagonists. Evidence on the metabolic
      and growth interference action by these agents, in addition to their smooth
      muscle-relaxing effects. The new action recognition emerges from data on the
      inhibitory effect of quinazoline-based antagonists on primary tumor growth and
      progression to metastasis. In addition to the cellular findings in the prostate,
      functional validation and therapeutic effects of selected lead pharmaceutically
      optimized derivatives in the context of impairing vascularity and triggering
      tumor apoptosis. EXPERT OPINION: Knowledge on targeting intracellular signalling
      pathways driving the cellular response via an alpha1-AR-dependent and independent
      antagonistic action, must be invested towards the optimization of new agents that
      while bypassing AR, exhibit improved pharmacological efficacy against human
      cancer.

PMID- 22148953
TI  - Delineating diseases by IMS-MS profiling of serum N-linked glycans.
AB  - Altered branching and aberrant expression of N-linked glycans is known to be
      associated with disease states such as cancer. However, the complexity of
      determining such variations hinders the development of specific glycomic
      approaches for assessing disease states. Here, we examine a combination of ion
      mobility spectrometry (IMS) and mass spectrometry (MS) measurements, with
      principal component analysis (PCA) for characterizing serum N-linked glycans from
      81 individuals: 28 with cirrhosis of the liver, 25 with liver cancer, and 28
      apparently healthy. Supervised PCA of combined ion-mobility profiles for several,
      to as many as 10 different mass-to-charge ratios for glycan ions, improves the
      delineation of diseased states. This extends an earlier study [J. Proteome
      Res.2008, 7, 1109-1117] of isomers associated with a single glycan (S(1)H(5)N(4))
      in which PCA analysis of the IMS profiles appeared to differentiate the liver
      cancer group from the other samples. Although performed on a limited number of
      test subjects, the combination of IMS-MS for different combinations of ions and
      multivariate PCA analysis shows promise for characterizing disease states.

PMID- 22148955
TI  - Heart attack risk perception biases among hypertension patients: the role of
      educational level and worry.
AB  - Risk biases such as comparative optimism (thinking one is better off than similar
      others) and risk inaccuracy (misestimating one's risk compared to one's
      calculated risk) for health outcomes are common. Little research has investigated
      racial or socioeconomic differences in these risk biases. Results from a survey
      of individuals with poorly controlled hypertension (N=813) indicated that
      participants showed (1) comparative optimism for heart attack risk by
      underestimating their heart attack risk compared to similar others, and (2) risk
      inaccuracy by overestimating their heart attack risk compared to their calculated
      heart attack risk. More highly educated participants were more comparatively
      optimistic because they rated their personal risk as lower; education was not
      related to risk inaccuracy. Neither race nor the federal poverty level was
      related to risk biases. Worry partially mediated the relationship between
      education and personal risk. Results are discussed as they relate to the existing
      literature on risk perception.

PMID- 22148954
TI  - Moderate joint loading reduces degenerative actions of matrix metalloproteinases
      in the articular cartilage of mouse ulnae.
AB  - Joint loading is a recently developed loading modality, which can enhance bone
      formation and accelerate healing of bone fracture. Since mechanical stimulation
      alters expression of matrix metalloproteinases (MMPs) in chondrocytes, a question
      addressed herein was, does joint loading alter actions of MMPs in the articular
      cartilage? We hypothesized that expression and activity of MMPs are regulated in
      a load-intensity-dependent manner and that moderate load scan downregulates MMPs.
      To test this hypothesis, a mouse elbow-loading model was employed. In the
      articular cartilage of an ulna, the mRNA levels of a group of MMPs as well as
      their degenerative activities were determined. The result revealed that elbow
      loading altered the expression and activities of MMPs depending on its loading
      intensity. Collectively, the data in this study indicate that 0.2 and 0.5 N joint
      loading significantly reduced the expression of multiple MMPs, that is, MMP-1,
      MMP-3, MMP-8, and MMP-13, and overall activities of collagenases or gelatinases
      in articular cartilage, while higher loads increased the expression and activity
      of MMP-1 and MMP-13. Furthermore, moderate loads at 1 N elevated the mRNA level
      of CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), but higher
      loads at 4 N did not induce a detectable amount of CITED2 mRNA. Since CITED2 is
      known to mediate the downregulation of MMP-1 and MMP-13, the result indicates
      that joint loading at moderate intensity reduces MMP activities through potential
      induction of CITED2. MMPs such as MMP-1 and MMP-13 are predominant collagenases
      in the pathology of osteoarthritis. Therefore, joint loading could offer an
      interventional regimen for maintenance of joint tissues.

PMID- 22148956
TI  - Breastfeeding support in child care: an international comparison of findings from
      Australia and the United States.
AB  - INTRODUCTION: Many women in industrialized countries return to work while their
      children are infants. This is often associated with decreased breastfeeding
      duration or exclusivity. In order to better understand the breastfeeding support
      activities in childcare settings, studies were undertaken in settings with very
      different levels of infant mortality, breastfeeding, and breastfeeding support:
      Adelaide, Australia, and Wake County, North Carolina. The researchers
      collaborated to explore, contrast, and compare their baseline data. METHODS:
      Available data on breastfeeding rates and infant mortality rates were explored
      for the two settings. In addition, the two childcare datasets were explored for
      common questions, and descriptive and chi(2) analyses were carried out. RESULTS:
      Similarities were found between the response from childcare settings providers in
      Australia and the United States. Rates of having at least one breastfeeding
      infant (70.6% vs. 66.3%), a place to breastfeed (90.7% vs. 95%), and a
      refrigerator for storage (100% vs. 100%) were similar for Adelaide and Wake
      County, respectively. Qualitative data from Adelaide also mirrored Wake County
      data in that providers in neither setting were actively promoting breastfeeding.
      However, the Adelaide data reflected significantly higher rates of encouragement
      (95.3% vs. 21.7%), written policy (77.8% vs. 20.8%), resource/materials
      distribution (76.6% vs. 1% and 93.8% vs. 17%), and training (44.4% vs. 13.9%).
      CONCLUSIONS: Childcare practices may reflect the environment of support, or lack
      thereof, for breastfeeding in the society as a whole. The similarities and
      differences seen in these settings may reflect both official guidance as well as
      the breastfeeding environment. There is much work to be done in the United States
      to come up to the same level of support for breastfeeding in child care and in
      other programs as is seen in Australia.

PMID- 22148957
TI  - Structure-activity relationship (SAR) development and discovery of potent indole
      based inhibitors of the hepatitis C virus (HCV) NS5B polymerase.
AB  - Starting with the indole-based C-3 pyridone lead HCV polymerase inhibitor 2,
      extensive SAR studies were performed at different positions of the indole core.
      The best C-5 groups were found to be compact and nonpolar moieties and that the C
      6 attachments were not affecting potency. Limited N-1 benzyl-type substituent
      studies indicated that the best substitutions were fluoro or methyl groups at 2'
      or 5' positions of the benzyl group. To improve pharmacokinetic (PK) properties,
      acylsulfonamides were incorporated as acid isosteres at the C-2 position. Further
      optimization of the combination at N-1, C-2, C-5, and C-6 resulted in the
      identification of compound 56, which had an excellent potency in both NS5B enzyme
      (IC(50) = 0.008 MUM) and cell-based replicon (EC(50) = 0.02 MUM) assays and a
      good oral PK profile with area-under-the curve (AUC) of 14 and 8 MUM.h in rats
      and dogs, respectively. X-ray structure of inhibitor 56 bound to the enzyme was
      also reported.

PMID- 22148959
TI  - Mechanical energy and power flow analysis of wheelchair use with different camber
      settings.
AB  - It has been suggested that minimisation of energy cost is one of the primary
      determinants of wheelchair designs. Wheel camber is one important parameter
      related to wheelchair design and its angle may affect usability during manual
      propulsion. However, there is little available literature addressing the effect
      of wheel camber on the mechanical energy or power flow involved in manual
      wheelchair propulsion. Twelve normal subjects (mean age, 22.3 years; SD, 1.6
      years) participated in this study. A video-tracking system and an instrumented
      wheel were used to collect 3D kinematic and kinetic data. Wheel camber of 0
      degrees  and 15 degrees  was chosen to examine the difference between mechanical
      power and power flow of the upper extremity during manual wheelchair propulsion.
      The work calculated from power flow and the discrepancy between the mechanical
      work and power flow work of upper extremity had significantly greater values with
      increased camber. The upper arm had a larger active muscle power compared with
      that in the forearm and hand segments. While propelling the increased camber, the
      magnitude of both the proximal and distal joint power and proximal muscle power
      was increased in all three segments. While the propelling wheel with camber not
      only needs a greater energy cost but also there is greater energy loss.

PMID- 22148958
TI  - Probing the orientation of electrostatically immobilized Protein G B1 by time-of
      flight secondary ion spectrometry, sum frequency generation, and near-edge X-ray
      adsorption fine structure spectroscopy.
AB  - To fully develop techniques that provide an accurate description of protein
      structure at a surface, we must start with a relatively simple model system
      before moving to increasingly complex systems. In this study, X-ray photoelectron
      spectroscopy (XPS), sum frequency generation spectroscopy (SFG), near-edge X-ray
      adsorption fine structure (NEXAFS) spectroscopy, and time-of-flight secondary ion
      mass spectrometry (ToF-SIMS) were used to probe the orientation of Protein G B1
      (6 kDa) immobilized onto both amine (NH(3)(+)) and carboxyl (COO(-))
      functionalized gold. Previously, we have shown that we could successfully control
      orientation of a similar Protein G fragment via a cysteine-maleimide bond. In
      this investigation, to induce opposite end-on orientations, a charge distribution
      was created within the Protein G B1 fragment by first substituting specific
      negatively charged amino acids with neutral amino acids and then immobilizing the
      protein onto two oppositely charged self-assembled monolayer (SAM) surfaces
      (NH(3)(+) and COO(-)). Protein coverage, on both surfaces, was monitored by the
      change in the atomic % N, as determined by XPS. Spectral features within the SFG
      spectra, acquired for the protein adsorbed onto a NH(3)(+)-SAM surface, indicates
      that this electrostatic interaction does induce the protein to form an oriented
      monolayer on the SAM substrate. This corresponded to the polarization dependence
      of the spectral feature related to the NEXAFS N(1s)-to-pi* transition of the beta
      sheet peptide bonds within the protein layer. ToF-SIMS data demonstrated a clear
      separation between the two samples based on the intensity differences of
      secondary ions stemming from amino acids located asymmetrically within Protein G
      B1 (methionine: 62 and 105 m/z; tyrosine: 107 and 137 m/z; leucine: 86 m/z). For
      a more quantitative examination of orientation, we developed a ratio comparing
      the sum of the intensities of secondary-ions stemming from the amino acid
      residues at either end of the protein. The 2-fold increase in this ratio,
      observed between the protein covered NH(3)(+) and COO(-) SAMs, indicates opposite
      orientations of the Protein G B1 fragment on the two different surfaces.

PMID- 22148960
TI  - The influence of amino acid sequence and functionality on the binding process of
      peptides onto gold surfaces.
AB  - We present a molecular dynamics study of the binding process of peptide A3
      (AYSSGAPPMPPF) and other similar peptides onto gold surfaces, and identify the
      functions of many amino acids. Our results provide a clear picture of the
      separate regimes present in the binding process: diffusion, anchoring, crawling
      and binding. Moreover, we explored the roles of individual residues. We found
      that tyrosine, methionine, and phenylalanine are strong binding residues; serine
      serves as an effective anchoring residue; proline acts as a dynamic anchoring
      point, while glycine and alanine give flexibility to the peptide backbone. We
      then show that our findings apply to unrelated phage-derived sequences that have
      been reported recently to facilitate AuNP synthesis. This new knowledge may aid
      in the design of new peptides for the synthesis of gold nanostructures with novel
      morphologies.

PMID- 22148961
TI  - Activation of mTOR signalling in young and old human skeletal muscle in response
      to combined resistance exercise and whey protein ingestion.
AB  - PURPOSE: To investigate the impact of whey protein ingestion and resistance
      exercise training on the phosphorylation of mRNA translational signalling
      proteins in the skeletal muscle of young and old men. METHODS: Sixteen healthy
      young (aged 18-25 years) and 15 healthy older men (aged 60-75 years) completed 12
      weeks of resistance exercise and were randomly assigned to consume a whey protein
      (WPI) or placebo drink after each session. Muscle biopsies were collected before
      and 2 h after an acute exercise bout at the beginning and the end of training.
      RESULTS: All subjects significantly increased strength after following strength
      training. Phosphorylation of mTOR was significantly greater in the WPI groups
      compared with placebo for both younger and older subjects. Phosphorylation of
      p70(S6K), eIF4G, and 4EBP1 was greater for older subjects consuming WPI.
      Phosphorylation of rpS6, eIF4G, and 4EBP1 tended to increase in the younger
      subjects that had consumed WPI. Post-training, younger subjects demonstrated a
      similar pattern of mTOR phosphorylation as seen pre-training. In contrast, the
      initial heightened phosphorylation of mTOR, p70(S6K), rpS6, and eIF4G in older
      muscle to combined resistance exercise and WPI ingestion became less pronounced
      after repeated training sessions. CONCLUSIONS: In the untrained state, resistance
      exercise coupled with WPI increases the phosphorylation of proteins involved in
      mRNA translation compared with exercise alone. Post-training, WPI- and exercise
      induced protein phosphorylation was reduced in older men, but not in younger men.
      Thus, strategies to induce hypertrophy should utilize protein and resistance
      training concurrently. Further investigations should delineate interventions that
      will maintain sensitivity to anabolic stimuli in older populations.

PMID- 22148962
TI  - Role of coronary artery calcification score on the decrease in GFR among subjects
      with CT coronary angiography.
AB  - OBJECTIVE: Higher levels of coronary artery calcification score (CACS) are
      associated not only with an increased risk for cardiovascular death, but also
      with lower glomerular filtration rates (GFRs). However, its role in renal disease
      progression in patients has not been elucidated. MATERIALS AND METHODS: We
      evaluated the change of estimated GFR in 279 nondialytic outpatients, who had
      undergone computed tomographic coronary angiography and follow-up over a period
      of 3 months. RESULTS: The mean age of the participants was 57.7 +/- 10.5 years,
      and the mean GFR was 88.2 +/- 15.7 mL/min/1.73 m(2). Although there was no
      difference in baseline GFR between the CACS <= 200 AU group (n = 240) and the
      CACS > 200 AU group (n = 39), the latter group had a lower level of final GFR and
      higher annual reduction rate of GFR than the former group after an observation
      period of 13.1 +/- 5.97 months. After adjusting for confounding variables,
      including age, gender, baseline GFR, albumin, and proteinuria, high levels of
      CACS showed an independent association with an annual reduction rate of GFR (r = 
      0.142, P = .048). CONCLUSIONS: The results suggest that CACS was related to an
      annual decrease in GFR and may predict the faster decline in GFR in patients with
      symptoms requiring computed tomographic coronary angiography.

PMID- 22148963
TI  - Emerging oral drugs for relapsing-remitting multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the
      central nervous system (CNS), traditionally considered to be an autoimmune,
      demyelinating disease. The last two decades have witnessed the introduction of
      several therapies for MS. At present, there are five licensed first-line, disease
      modifying drugs (DMDs) in MS and two second-line treatments. Nevertheless, in
      clinical practice DMDs or immunosuppressive treatments are frequently associated
      with suboptimal response in terms of efficacy and several side effects leading to
      poor patient adherence. AREAS COVERED: Since MS is a chronic disease, DMDs
      require long-term, regular injection or monthly parenteral infusions, which may
      be uncomfortable and inconvenient for the patient. Thus, there is an important
      need for new therapeutic strategies, especially those that may offer greater
      patient satisfaction in order to optimize therapeutic outcomes. Currently, five
      oral therapies are in Phase III development or have recently been approved for
      the treatment of relapsing-remitting MS: cladribine and fingolimod, the first
      approved in Russia and Australia, the latter is more widespread. Fumaric acid (BG
      12), teriflunomide (A77126 or HMR1726) and laquinimod (ABR-215062) are in Phase
      III trials. Details of these five drugs will be covered in this review. EXPERT
      OPINION: Preliminary results indicate that oral medications are as effective as,
      or possibly more effective than, current injectable formulations. It is
      believable that improved outcomes will translate into higher real and perceived
      efficacy rates and contribute to improved adherence. The decision to switch
      established patients from injectable to oral medications will be made on
      balancing the efficacy and tolerability of the patient's existing therapy and
      their compliance history, even though safety is likely to become the most
      important factor in the future development of MS drugs.

PMID- 22148971
TI  - Standardization of the Tanner-Whitehouse bone age method in the context of
      automated image analysis.
AB  - BACKGROUND/AIMS: The Tanner-Whitehouse (TW) method for bone age determination has
      been the basis for many population studies and it is used in many clinics.
      However, TW bone age raters can differ systematically from each other. The aim of
      the study was to present a new standard version of TW bone age rating implemented
      by the automated BoneXpert method and calibrated on the manual TW stage ratings
      of the First Zurich Longitudinal Study. SUBJECTS: Hand radiographs of 231
      children born in 1954-1956 were recorded annually from an average age of 5-20
      years. For validation, 76 X-rays of Tanner's original Gold Series from eight boys
      were used. RESULTS: The root mean square deviation between manual and automated
      TW ratings in the Zurich data was 0.67 years for boys in the TW bone age range 5
      15 years and 0.63 years for girls, 5-14 years. The new standard TW rating differs
      systematically from two previous TW versions of the automated method, based on
      different raters. CONCLUSION: The new automated TW ratings show good accuracy
      relative to the manual ratings of the Zurich data and the Gold Series. There are
      significant differences between manual TW raters, an effect which is eliminated
      with the automated method.

PMID- 22148972
TI  - Intrapleural chemo- and hyperthermotherapies for malignant pleural effusion: a
      randomized prospective study.
AB  - OBJECTIVE: The current prospective randomized study was designed to evaluate the
      safety and efficacy of combined intrapleural cisplatin and OK-432 (picibanil)
      plus hyperthermotherapy in patients with malignant pleural effusion (MPE).
      METHODS: A total of 358 patients with MPE due to end-stage malignancies were
      enrolled and randomly divided into two groups, A and B: the intrapleural
      combination of cisplatin and OK-432 with hyperthermotherapy (n = 179) or without
      hyperthermotherapy (n = 179), respectively. Mild toxicities such as nausea,
      vomiting or anorexia, bone marrow depression, and pyrexia were similar in both
      groups. RESULT: Patients in Group A (with hyperthermotherapy) showed a
      significantly higher overall response (93.4%) compared to those in Group B
      (79.8%, chi(2) = 43.11, p < .05). The median survival time for patients in Group
      A and Group B were 8.9 and 6.2 months, respectively (p > .05). After treatment,
      the quality of life scores were significantly increased in both groups as
      compared to prior treatment (p < .05). CONCLUSION: In conclusion, our study
      suggests that combined intrapleural cisplatin and OK-432 followed by
      hyperthermotherapy are more effective in the control of MPE and improve patients'
      quality of life.

PMID- 22148973
TI  - Determinants and causes of mortality in HIV-infected patients receiving
      antiretroviral therapy in Burkina Faso: a five-year retrospective cohort study.
AB  - In this study, we investigated the causes of death and the factors associated
      with mortality in a cohort of patients receiving highly active antiretroviral
      therapy (HAART) in Burkina Faso, an African country with limited resources. This
      retrospective cohort study included patients aged 15 years and older who started
      HAART for the first time between January 2003 and December 2008 in 14 health
      districts. We used survival analyses, including the Kaplan-Meier method, to
      examine potential predictors of death and two Cox proportional hazard models to
      estimate hazard ratios for death, first from baseline covariates and then from
      time-dependent covariates. A total of 6641 patients initiated HAART during this
      period; of these, 5608 were included in the analysis. By the end of the study
      period, 4310 of those patients were still receiving HAART, 690 had died, 207 had
      been transferred and 401 were lost to follow-up. The median duration of follow-up
      was 23.2 months [interquartile range (IQR): 12.4-36.9], and the overall incidence
      of mortality was 6 per 100 person-years. The clinical stage, CD4 count, body mass
      index (BMI), haemoglobin level, HAART regimen, gender, age, profession and year
      of initiation were the primary risk factors associated with death. In the
      multivariate analysis, BMI, clinical stage, treatment regimen and CD4 count
      remained significantly associated with death. The most frequent causes of death
      were wasting syndrome, tuberculosis and anaemia. This result highlights the
      already advanced stage of immunodeficiency among patients in Burkina Faso when
      they start HAART. Testing patients for HIV and starting antiretroviral therapy
      earlier are necessary to further reduce the mortality of patients living with
      HIV. This study provides a solid evidence base with which future evaluations of
      HAART in Burkina Faso can be compared.

PMID- 22148974
TI  - Functionally diverse nucleophilic trapping of iminium intermediates generated
      utilizing visible light.
AB  - Our previous studies into visible-light-mediated aza-Henry reactions demonstrated
      that molecular oxygen played a vital role in catalyst turnover as well as the
      production of base to facilitate the nucleophilic addition of nitroalkanes.
      Herein, improved conditions for the generation of iminium ions from
      tetrahydroisoquinolines that allow for versatile nucleophilic trapping are
      reported. The new conditions provide access to a diverse range of functionality
      under mild, anaerobic reaction conditions as well as mechanistic insights into
      the photoredox cycle.

PMID- 22148978
TI  - betahCG and PAPP-A in first trimester: predictive factors for preeclampsia?
AB  - OBJECTIVE: The aim of our study was to investigate a possible correlation between
      the expression of the placenta-secreted hormones, beta-subunit of human chorionic
      gonadotrophin (betahCG) and pregnancy-associated plasma protein A (PAPP-A),
      during the first trimester screening and the development of preeclampsia.
      METHODS: A total of 155 patients between 11 + 0 and 13 + 6 weeks of gestation
      were enrolled in this study. PAPP-A and betahCG levels were measured using the
      KRYPTOR(r) system. RESULTS: The serum levels of betahCG were significantly higher
      in pregnancies which subsequently developed preeclampsia. The PAPP-A
      concentration did not differ significantly in pregnancies complicated by
      preeclampsia than in uncomplicated pregnancies. CONCLUSION: These results might
      contribute to developing new tests in the prediction of preeclampsia.

PMID- 22148979
TI  - Outcomes among older people in a post-acute inpatient rehabilitation unit.
AB  - PURPOSE: Designated multidisciplinary rehabilitation units have been shown to
      provide several benefits for the frail older population. The aim of this research
      was to evaluate changes in strength, mobility, balance, endurance, frailty and
      quality of life (QoL) following a 6-week multidisciplinary inpatient
      rehabilitation programme. METHOD: This was a prospective, observational study
      performed in a post-acute multidisciplinary geriatric inpatient rehabilitation
      service. A consecutive sample of heterogenous frail older adults (n = 32)
      participated. Subjects were assessed on admission to the rehabilitation service
      (T1) and following 6 weeks of rehabilitation (T2). A range of outcome measures
      were used to assess function and QoL: Berg Balance Scale (BBS), Timed Up and Go
      (TUG), 6-Minute Walk Test (6MWT), Barthel Index (BI), EuroQol-Visual Analogue
      Scale (EQ-VAS), Clinical Frailty Scale (CFS), lower limb and grip dynamometry.
      RESULTS: The majority were female (n = 25), the mean age was 82.9 years (SD
      6.35). The median length of stay was 49 days. Patients improved significantly
      between T1 and T2 assessments in the BBS (p <= 0.0001); TUG (p <= 0.0001); 6MWT
      (p <= 0.0001); BI (p <= 0.0001); EQ-VAS (p = 0.002); CFS (p <= 0.0001); and in
      some aspects of grip and lower limb strength. CONCLUSION: This study has
      demonstrated that positive outcomes occurred in a range of measures in an older,
      frail inpatient rehabilitation population.

PMID- 22148980
TI  - Transmission by super-spreading event of pandemic A/H1N1 2009 influenza during
      road and train travel.
AB  - The investigation of clustered cases of pandemic A/H1N1 2009 influenza virus
      infection (21 children, 3 adults) during a summer camp, led to the identification
      of transportation as the circumstance of transmission. Results suggest that super
      spreading of flu can occur in a confined space without sufficient air renewal.

PMID- 22148981
TI  - 'Giant' CdSe/CdS core/shell nanocrystal quantum dots as efficient
      electroluminescent materials: strong influence of shell thickness on light
      emitting diode performance.
AB  - We use a simple device architecture based on a poly(3,4
      ethylendioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-coated indium tin oxide
      anode and a LiF/Al cathode to assess the effects of shell thickness on the
      properties of light-emitting diodes (LEDs) comprising CdSe/CdS core/shell
      nanocrystal quantum dots (NQDs) as the emitting layer. Specifically, we are
      interested in determining whether LEDs based on thick-shell nanocrystals, so
      called "giant" NQDs, afford enhanced performance compared to their counterparts
      incorporating thin-shell systems. We observe significant improvements in device
      performance as a function of increasing shell thickness. While the turn-on
      voltage remains approximately constant for all shell thicknesses (from 4 to 16
      CdS monolayers), external quantum efficiency and maximum luminance are found to
      be about one order of magnitude higher for thicker shell nanocrystals (>=13 CdS
      monolayers) compared to thinner shell structures (<9 CdS monolayers). The
      thickest-shell nanocrystals (16 monolayers of CdS) afforded an external quantum
      efficiency and luminance of 0.17% and 2000 Cd/m(2), respectively, with a
      remarkably low turn-on voltage of ~3.0 V.

PMID- 22148982
TI  - Effect of resveratrol on Bcl-2 and VEGF expression in oxygen-induced retinopathy
      of prematurity.
AB  - PURPOSE: To explore the effect of resveratrol on B-cell leukemia/lymphoma-2 (Bcl
      2) and vascular endothelial growth factor (VEGF) expression in rats with oxygen
      induced retinopathy of prematurity (ROP). METHODS: Seven-day-old Sprague-Dawley
      rats (N = 60) were randomly assigned to five groups. Group A received normal
      partial oxygen pressure and groups B, C, D, and E received 75% +/- 2% oxygen for
      5 days to induce ROP. The rats in groups C, D, and E were intragastrically
      treated with resveratrol (10, 30, and 60 mg/kg/d, respectively) once daily for 5
      days. Rats were killed at 17 days of age and the retina was collected. RESULTS:
      Western blot analysis revealed increased Bcl-2 protein expression in group B
      versus group A. Levels of Bcl-2 decreased with the increase of resveratrol
      concentration in groups C, D, and E. The optical density of Bcl-2 protein
      expression in group B was four times higher than that in group A (P < .01). When
      compared with group B, expression of Bcl-2 and VEGF in groups C, D, and E
      decreased in a dose-dependent manner. Significant differences in expression of
      Bcl-2 and VEGF were also noted among the three treatment groups with resveratrol
      (P < .01). After treatment with resveratrol at 10, 30, and 60 mg/kg/d, the
      inhibition rate of Bcl-2 expression was 11.1%, 38.1%, and 69.8% and that of VEGF
      expression was 3.4%, 23.0%, and 43.7%, respectively. CONCLUSION: Resveratrol can
      significantly inhibit expression of Bcl-2 and VEGF in the retina of neonatal rats
      with oxygen-induced ROP. It may provide a protective effect on retinal
      neovascular diseases, including ROP.

PMID- 22148983
TI  - Psychometric properties of the Activities-Specific Balance Confidence Scale in
      persons 0-14 days and 3 months post stroke.
AB  - PURPOSE: To test the internal consistency and validity of a Swedish translation
      of the Activities-specific Balance Confidence Scale (ABC) 0-14 days and 3 months
      post stroke. METHOD: 37 persons were tested at 0-14 days (median 5 days) post
      stroke and 31 were retested 3 months later (median 87 days). In addition to the
      ABC, the Functional Ambulation Categories, modified Rivermead Mobility Index,
      timed up and go test, 10-meter timed walk, SF-36 and the 12-item Walking Scale
      were used. RESULTS: The internal consistency was high at alpha = 0.94 to 0.97.
      Kendall correlation-tau coefficients were moderate and varied somewhat depending
      on time poststroke. At 0-14 days post stroke the highest correlation was found
      between the ABC and the 12-item Walking Scale (-0.55, p < 0.01). At 3 months
      poststroke, the correlations with the Functional Ambulation Categories was 0.49
      (p < 0.01), timed up and go test -0.43 (p < 0.01), 10-meter timed walk -0.41 (p <
      0.01), and modified Rivermead Mobility Index 0.46 (p < 0.01). Divergent validity
      was established by the non-significant correlation (0.12) between the ABC and SF
      36 mental component summary. CONCLUSIONS: The Swedish version of ABC has high
      internal consistency and is valid for measuring balance confidence in the acute
      and sub acute phases of stroke.

PMID- 22148984
TI  - Comprehensive description of the N-glycoproteome of mouse pancreatic beta-cells
      and human islets.
AB  - Cell surface N-glycoproteins provide a key interface of cells to their
      environment and therapeutic entry points for drug and biomarker discovery. Their
      comprehensive description denotes therefore a formidable challenge. The beta
      cells of the pancreas play a crucial role in blood glucose homeostasis, and
      disruption of their function contributes to diabetes. By combining cell surface
      and whole cell capturing technologies with high-throughput quantitative proteomic
      analysis, we report on the identification of a total of 956 unique N
      glycoproteins from mouse MIN6 beta-cells and human islets. Three-hundred-forty
      nine of these proteins encompass potential surface N-glycoproteins and include
      orphan G-protein-coupled receptors, novel proteases, receptor protein kinases,
      and phosphatases. Interestingly, stimulation of MIN6 beta-cells with glucose and
      the hormone GLP1, known stimulators of insulin secretion, causes significant
      changes in surface N-glycoproteome expression. Taken together, this beta-cell N
      glycoproteome resource provides a comprehensive view on the composition of beta
      cell surface proteins and expands the scope of signaling systems potentially
      involved in mediating responses of beta-cells to various forms of
      (patho)physiologic stress and the extent of dynamic remodeling of surface N
      glycoprotein expression associated with metabolic and hormonal stimulation.
      Moreover, it provides a foundation for the development of diabetes medicines that
      target or are derived from the beta-cell surface N-glycoproteome.

PMID- 22148985
TI  - Severe paramethoxymethamphetamine (PMMA) and paramethoxyamphetamine (PMA)
      outbreak in Israel.
AB  - CONTEXT: Paramethoxymethamphetamine (PMMA) is a hallucinogenic synthetic
      substituted amphetamine that was not included in the Israeli Controlled Substance
      Act (CSA). OBJECTIVE: To report a severe PMMA and paramethoxyamphetamine (PMA)
      outbreak. PATIENTS AND METHODS: The Israeli national forensic toxicology
      laboratory analyzes the body fluids of unnatural deaths by means of screening
      immunoassays and chromatographic confirmation and quantification. Samples are
      referred to this laboratory by the Israeli Forensic Medicine Institute and by
      hospitals following consultation with the Israel Poison Information Center. The
      forensic toxicology laboratory began determining PMMA and PMA in February 2007.
      In all fatal cases with a positive immunoassay screen for amphetamines, a
      chromatographic analysis of PMA and PMMA was performed. The laboratory and
      demographic data of consecutive patients in whom PMMA or PMA were detected, were
      collected during 1 year and subjected to descriptive analysis. RESULTS: Of 108
      fatal cases with a positive screen for amphetamines, 32 were confirmed. Twenty
      four of the 32 cases tested positive for PMMA and PMA--age 27 +/- 5 years, 79.2%
      males, post mortem whole blood PMMA and PMA concentrations 0.35 +/- 0.24 and 2.72
      +/- 1.67 mcg/mL, respectively. Co-exposures were detected in 17 (70.8%)
      fatalities; including methylenedioxymethamphetamine, methylenedioxyamphetamine,
      cocaine, cannabinoids, cathinone derivatives, ephedrine/pseudoephedrine, opiates,
      and ethanol. In addition, five non-fatal male cases were identified; age 32 +/- 5
      years, four had co-exposures to cocaine, cathinone derivatives, and cannabinoids.
      These findings led to the inclusion of PMMA in the CSA in July 2007, resulting in
      only three more fatalities in the following year. DISCUSSION: We report an
      outbreak of PMMA and PMA poisoning resulting in 24 fatalities, and the post
      mortem whole blood and urine concentrations of these two compounds. PMA was
      probably the result of PMMA metabolism. Stimulant co-exposures may have
      contributed to the severity of the poisoning. CONCLUSION: Forensic laboratory and
      poison center co-operation is important in identifying a new drug of abuse.

PMID- 22148986
TI  - Is maternal opioid use hazardous to breast-fed infants?
AB  - Over the last few decades, the rate of breastfeeding has increased steadily in
      the developed countries of the world. During this time, opioid use in the general
      population has steadily increased as well. Despite this, clinicians remain
      unclear whether opioid use is safe during breastfeeding. While the vast majority
      of medications used during breastfeeding occur without incident, case reports and
      studies have reported possible opioid toxicity in breast-fed infants. Multiple
      enzymes are involved in the metabolism of opioids. CYP2D6 catabolizes O
      demethylation of codeine, tramadol, oxycodone, and hydrocodone to more potent
      metabolites. CYP3A4 inactivates methadone, meperidine, and buprenorphine.
      Glucoronide conjugation by the UGT enzyme family inactivates morphine and
      hydromorphone. Genetic polymorphisms and interfering medications affect the
      maternal metabolism, which in turn determines the exposure and risk to the breast
      fed neonate. We review the production of breast milk, the transfer of xenobiotics
      from blood to milk, the characteristics that alter xenobiotic breast-milk
      concentrations, and we review the evidence of specific common opioids and infant
      toxicity. The short-term maternal use of prescription opioids is usually safe and
      infrequently presents a hazard to the newborn.

PMID- 22148988
TI  - Anxiety reactivity and anxiety perseveration represent dissociable dimensions of
      trait anxiety.
AB  - Trait anxiety is an individual-difference variable reflecting variation in state
      anxiety elevations resulting from exposure to a stressor. It is usually measured
      using questionnaire instruments, such as the Spielberger State-Trait Anxiety
      Inventory (STAI-T). The present research conceptually distinguishes, and
      independently assesses, two hypothetical dimensions of anxiety vulnerability
      which, it is argued, could plausibly make independent contributions to variance
      in trait-anxiety scores. These dimensions are anxiety reactivity, the probability
      of experiencing an anxiety reaction to a stressor, and anxiety perseveration, the
      persistence of anxiety symptoms once elicited. Participants were asked three
      questions about each STAI-T item. The traditional STAI-T question assessed how
      much of the time this symptom was experienced; the anxiety-reactivity question
      assessed the probability of experiencing the symptom in response to a stressor;
      and the anxiety-perseveration question assessed how long the symptom persisted,
      if elicited. Regression analysis determined that anxiety reactivity and anxiety
      perseveration scores both accounted for independent variance in trait-anxiety
      scores. It is argued that models of anxiety vulnerability should seek to
      differentiate both the causes and the consequences of elevated anxiety reactivity
      and increased anxiety perseveration.

PMID- 22148990
TI  - Unpacking cognitive reappraisal: goals, tactics, and outcomes.
AB  - Studies of emotion regulation typically contrast two or more strategies (e.g.,
      reappraisal vs. suppression) and ignore variation within each strategy. To
      address such variation, we focused on cognitive reappraisal and considered the
      effects of goals (i.e., what people are trying to achieve) and tactics (i.e.,
      what people actually do) on outcomes (i.e., how affective responses change). To
      examine goals, we randomly assigned participants to either increase positive
      emotion or decrease negative emotion to a negative stimulus. To examine tactics,
      we categorized participants' reports of how they reappraised. To examine
      reappraisal outcomes, we measured experience and electrodermal responding.
      Findings indicated that (a) the goal of increasing positive emotion led to
      greater increases in positive affect and smaller decreases in skin conductance
      than the goal of decreasing negative emotion, and (b) use of the reality
      challenge tactic was associated with smaller increases in positive affect during
      reappraisal. These findings suggest that reappraisal can be implemented in the
      service of different emotion goals, using different tactics. Such differences are
      associated with different outcomes, and they should be considered in future
      research and applied attempts to maximize reappraisal success.

PMID- 22148989
TI  - Contemplative/emotion training reduces negative emotional behavior and promotes
      prosocial responses.
AB  - Contemplative practices are believed to alleviate psychological problems,
      cultivate prosocial behavior and promote self-awareness. In addition,
      psychological science has developed tools and models for understanding the mind
      and promoting well-being. Additional effort is needed to combine frameworks and
      techniques from these traditions to improve emotional experience and
      socioemotional behavior. An 8-week intensive (42 hr) meditation/emotion
      regulation training intervention was designed by experts in contemplative
      traditions and emotion science to reduce "destructive enactment of emotions" and
      enhance prosocial responses. Participants were 82 healthy female schoolteachers
      who were randomly assigned to a training group or a wait-list control group, and
      assessed preassessment, postassessment, and 5 months after training completion.
      Assessments included self-reports and experimental tasks to capture changes in
      emotional behavior. The training group reported reduced trait negative affect,
      rumination, depression, and anxiety, and increased trait positive affect and
      mindfulness compared to the control group. On a series of behavioral tasks, the
      training increased recognition of emotions in others (Micro-Expression Training
      Tool), protected trainees from some of the psychophysiological effects of an
      experimental threat to self (Trier Social Stress Test; TSST), appeared to
      activate cognitive networks associated with compassion (lexical decision
      procedure), and affected hostile behavior in the Marital Interaction Task. Most
      effects at postassessment that were examined at follow-up were maintained
      (excluding positive affect, TSST rumination, and respiratory sinus arrhythmia
      recovery). Findings suggest that increased awareness of mental processes can
      influence emotional behavior, and they support the benefit of integrating
      contemplative theories/practices with psychological models and methods of emotion
      regulation.

PMID- 22148991
TI  - Perceptual, not memorial, disruption underlies emotion-induced blindness.
AB  - Emotion-induced blindness refers to impaired awareness of stimuli appearing in
      the temporal wake of an emotionally arousing stimulus (S. B. Most, Chun, Widders,
      & Zald, 2005). In previous emotion-induced blindness experiments, participants
      withheld target responses until the end of a rapid stream of stimuli, even though
      each target appeared in the middle of the stream. The resulting interval between
      the targets' offset and participants' initiation of a response leaves open the
      possibility that emotion-induced blindness reflects a failure to encode or
      maintain target information in memory rather than a failure of perception. In the
      present study, participants engaged in a typical emotion-induced blindness task
      but initiated a response immediately upon seeing each target. Emotion-induced
      blindness was nevertheless robust. This suggests that emotion-induced blindness
      is not attributable to the delay between awareness of a target and the initiation
      of a response, but rather reflects the disruptive impact of emotional distractors
      on mechanisms driving conscious perception.

PMID- 22148992
TI  - Class and compassion: socioeconomic factors predict responses to suffering.
AB  - Previous research indicates that lower-class individuals experience elevated
      negative emotions as compared with their upper-class counterparts. We examine how
      the environments of lower-class individuals can also promote greater
      compassionate responding-that is, concern for the suffering or well-being of
      others. In the present research, we investigate class-based differences in
      dispositional compassion and its activation in situations wherein others are
      suffering. Across studies, relative to their upper-class counterparts, lower
      class individuals reported elevated dispositional compassion (Study 1), as well
      as greater self-reported compassion during a compassion-inducing video (Study 2)
      and for another person during a social interaction (Study 3). Lower-class
      individuals also exhibited heart rate deceleration-a physiological response
      associated with orienting to the social environment and engaging with others
      during the compassion-inducing video (Study 2). We discuss a potential mechanism
      of class-based influences on compassion, whereby lower-class individuals' are
      more attuned to others' distress, relative to their upper-class counterparts.

PMID- 22148993
TI  - Trait anxiety focuses spatial attention.
AB  - Some findings suggest that trait anxiety impairs selective attention (e.g., Fox,
      1993) while others suggest the opposite (e.g., Murray & Janelle, 2003). Both
      views may hold some truth if trait anxiety affects different levels of selective
      attention in opposite directions: trait anxiety might improve spatial attention,
      or perceptual selection, but weaken postperceptual selection. We used an
      adaptation of the flanker task (Eriksen & Hoffman, 1973) which distinguishes
      between spatial attention and postperceptual selection (Caparos & Linnell, 2010)
      to test this hypothesis. Trait anxiety was found to improve spatial attention but
      not to affect post-perceptual selection. The latter null effect may have resulted
      from the relatively high perceptual load used in this study. The focusing effect
      of trait anxiety suggests that anxiety reduces perceptual resources or increases
      cognitive engagement.

PMID- 22148994
TI  - Genetic moderation of sensitivity to positive and negative affect in marriage.
AB  - Hypothesizing that genetic factors partially govern sensitivity to interpersonal
      cues, we examined whether a polymorphism (5-HTTLPR) in the serotonin transporter
      gene would moderate spouses' sensitivity to positive and negative partner affect.
      Before and after marital discussions, participants from 76 couples (total n =
      150) reported their affective states. Spouses carrying the short allele of the 5
      HTTLPR were more responsive to their partner's preinteraction positive affect and
      anxiety/nervousness, compared with spouses with two long alleles. These data
      support the contention that the serotonin system influences affective responses
      to social stimuli. In contrast to the view that the 5-HTTLPR primarily affects
      response to adverse experiences, these results suggest that this polymorphism
      moderates sensitivity to positive as well as negative affect.

PMID- 22148995
TI  - Relationship between language competence and emotional competence in middle
      childhood.
AB  - Research on children's emotional competence has received considerable attention
      in the last decade, including the role of language. Language competence (LC) and
      emotional competence (EC) comprise multiple components. These components and
      their specific interrelations have not been studied sufficiently. In our study,
      we examined relations between multiple components of LC and EC in a sample of 210
      school-age children. Five measures represented LC: receptive vocabulary, verbal
      fluency, literacy, narrative structure, and the narrative use of evaluative
      devices. Four measures represented EC: expressive emotion vocabulary, declarative
      emotion knowledge, awareness of mixed emotions, and facial emotion recognition.
      Results showed strong positive correlations between LC and EC ranging between r =
      .12 and r = .45. In particular, receptive vocabulary and literacy were closely
      related to emotion knowledge and awareness of mixed emotions. A confirmatory
      factor analysis revealed that there is a common general ability factor for LC and
      EC. We discuss why receptive vocabulary and literacy might be so strongly related
      to emotion knowledge in school-age children. Our findings have implications for
      developmental psychologists, educational research, and speech-language
      pathologists.

PMID- 22148996
TI  - Mindfulness and its relationship to emotional regulation.
AB  - Research on the effectiveness and mechanisms of mindfulness training applied in
      psychotherapy is still in its infancy (Erisman & Roemer, 2010). For instance,
      little is known about the extent and processes through which mindfulness practice
      improves emotion regulation. This experience sampling study assessed the
      relationship between mindfulness, emotion differentiation, emotion lability, and
      emotional difficulties. Young adult participants reported their current emotional
      experiences 6 times per day during 1 week on a PalmPilot device. Based on these
      reports of emotions, indices of emotional differentiation and emotion lability
      were composed for negative and positive emotions. Mindfulness was associated with
      greater emotion differentiation and less emotional difficulties (i.e., emotion
      lability and self-reported emotion dysregulation). Mediational models indicated
      that the relationship between mindfulness and emotion lability was mediated by
      emotion differentiation. Furthermore, emotion regulation mediated the
      relationship between mindfulness and both negative emotion lability and positive
      emotion differentiation. This experience sampling study indicates that self
      reported levels of mindfulness are related to higher levels of differentiation of
      one's discrete emotional experiences in a manner reflective of effective emotion
      regulation.

PMID- 22148997
TI  - The eyes have it: making positive expressions more positive and negative
      expressions more negative.
AB  - Facial expressions frequently involve multiple individual facial actions. How do
      facial actions combine to create emotionally meaningful expressions? Infants
      produce positive and negative facial expressions at a range of intensities. It
      may be that a given facial action can index the intensity of both positive
      (smiles) and negative (cry-face) expressions. Objective, automated measurements
      of facial action intensity were paired with continuous ratings of emotional
      valence to investigate this possibility. Degree of eye constriction (the Duchenne
      marker) and mouth opening were each uniquely associated with smile intensity and,
      independently, with cry-face intensity. In addition, degree of eye constriction
      and mouth opening were each unique predictors of emotion valence ratings. Eye
      constriction and mouth opening index the intensity of both positive and negative
      infant facial expressions, suggesting parsimony in the early communication of
      emotion.

PMID- 22148998
TI  - Immediacy bias in social-emotional comparisons.
AB  - In seven studies of naturally occurring, "real-world" emotional events, people
      demonstrated an immediacy bias in social-emotional comparisons, perceiving their
      own current or recent emotional reactions as more intense compared with others'
      emotional reactions to the same events. The events examined include crossing a
      scary bridge (study 1a), a national tragedy (study 1b), terrorist attacks
      (studies 2a and 3b), a natural disaster (study 2b), and a presidential election
      (study 3b). These perceived differences between one's own and others' emotions
      declined over time, as relatively immediate and recent emotions subsided, a
      pattern that people were not intuitively aware of (study 2c). This immediacy bias
      in social-emotional comparisons emerged for both explicit comparisons (studies
      1a, 1b, and 3b), and for absolute judgments of emotional intensity (studies 2a,
      2b, and 3a). Finally, the immediacy bias in social-emotional comparisons was
      reduced when people were reminded that emotional display norms might lead others'
      appearances to understate emotional intensity (studies 3a and 3b). Implications
      of these findings for social-emotional phenomena are discussed.

PMID- 22148999
TI  - Raphael Meldola, his blue and his times.
AB  - Raphael Meldola (1849-1915), English industrial and academic chemist,
      spectroscopist, naturalist, educator and lobbyist for science, is today almost a
      forgotten scientist whose life is celebrated only with a medal awarded by the
      Royal Society of Chemistry that honors achievement by younger chemists. In the
      1870-80s, however, he invented a number of important synthetic dyestuffs
      including the cotton dyes isamine blue and Meldola's blue, and also naphthol
      green B, all of which have had application in biology and medicine. I describe
      here the early emergence of the synthetic dye industry, the first science-based
      industry, Meldola's role in its development, and his own inventions. Meldola's
      wide ranging achievements in science led to appointments as president of
      important professional scientific and manufacturers' societies. He was a fervent
      disciple of natural selection, a correspondent of Charles Darwin, and a prominent
      19(th)-century neo-Darwinian. In 1886, drawing on analogies with evolutionary
      theory, he warned the British that neglect of science, particularly chemistry,
      would lead to industrial decline and even extinction, though his message
      generally was ignored, at least until 1914.

PMID- 22149000
TI  - Emerging pharmacotherapy of tinnitus.
AB  - One in ten adults has clinically significant subjective tinnitus, and for one in
      hundred, tinnitus severely affects their quality of life. Despite the significant
      unmet clinical need for a safe and effective drug targeting tinnitus relief,
      there is currently not a single FDA-approved drug on the market. Even a drug that
      produces a small but significant effect would have a huge therapeutic impact. In
      the last few years, there have been significant advances in i) the understanding
      of the pathophysiology of the different forms of tinnitus, ii) the establishment
      of valid animal models and iii) the development of clinical trial methodology. A
      glimpse of hope is appearing in the horizon as an increasing number of
      pharmaceutical industries now have compounds targeting tinnitus in their
      pipeline.

PMID- 22149001
TI  - Surface-initiated synthesis of poly(3-methylthiophene) from indium tin oxide and
      its electrochemical properties.
AB  - Poly(3-methylthiophene) (P3MT) was synthesized directly from indium tin oxide
      (ITO) electrodes modified with a phosphonic acid initiator, using Kumada catalyst
      transfer polymerization (KCTP). This work represents the first time that polymer
      thickness has been controlled in a surface initiated KCTP reaction, highlighting
      the utility of KCTP in achieving controlled polymerizations. Polymer film
      thicknesses were regulated by the variation of the solution monomer concentration
      and ranged from 30 to 265 nm. Electrochemical oxidative doping of these films was
      used to manipulate their near surface composition and effective work function.
      Doped states of the P3MT film are maintained even after the sample is removed
      from solution and potential control confirming the robustness of the films. Such
      materials with controllable thicknesses and electronic properties have the
      potential to be useful as interlayer materials for organic electronic
      applications.

PMID- 22149002
TI  - Evaluating a suitable level of model complexity for finite element analysis of
      the intact acetabulum.
AB  - To enable large-scale multi-factorial finite element (FE) studies, the FE models
      used must be as computationally efficient as is feasible, while maintaining a
      suitable level of definition. The present study seeks to find an optimum level of
      model complexity for use in such large-scale studies by investigating which model
      attributes are most influential over the chosen model outputs of principal stress
      and strain in the intact acetabulum. A multi-factorial sensitivity study was
      carried out using 128 FE models, representing combinations of the following
      variables: bone stiffness distribution, imposed muscle loading, boundary
      condition location, hip joint contact conditions and patient's bone anatomy. The
      relative sensitivity of each input factor was analysed, and it was concluded that
      the optimum level of model definition must include CT-dependent trabecular bone
      properties and a sliding interface at the hip joint. It was found that it was not
      essential to describe the ligamentous sacroiliac and pubic symphysis joints;
      these could be rigidly fixed in space; and for the normal walking load case,
      muscle forces may be neglected. It was also concluded that a variety of bone
      anatomies should be included in a multi-factorial analysis if results are to be
      inferred for a wider population. 

PMID- 22149003
TI  - Olmesartan medoxomil is associated with decreased plasma AGEs, pentosidine, and N
      (epsilon)-carboxymethyl-lysine levels in hemodialysis patients.
AB  - BACKGROUND: Advanced glycation end products (AGEs) are associated with
      comorbidity and death among patients on hemodialysis (HD). Angiotensin II type 1
      receptor blockers (ARBs) can decrease the formation of AGEs in vitro. This study
      examines the ability of various ARBs to decrease plasma AGE levels in
      hypertensive patients on HD. METHODS: This preliminary randomized prospective
      study included 24 hypertensive patients on HD who were treated with candesartan
      (8 mg/day). The patients were randomly assigned to an olmesartan (20 mg/day, n =
      12) or a telmisartan (40 mg/day, n = 12) group and followed up 24 weeks. Blood
      pressure was monitored before each HD session, and plasma pentosidine, N
      (epsilon)-carboxymethyl-lysine (CML), serum malondialdehyde-low-density
      lipoprotein (LDL), high-sensitive CRP, and serum total free radical (TFR) were
      measured at baseline, and at 4, 12, and 24 weeks. RESULTS: Olmesartan was
      significantly associated with decreased systolic blood pressure compared with
      telmisartan. After 24 weeks of treatment, plasma pentosidine and CML levels were
      significantly decreased and serum TFR levels tended to be decreased in the
      olmesartan group, but remained unchanged in the telmisartan group. CONCLUSIONS:
      These results suggest that olmesartan can help to decrease plasma AGE levels in
      patients on HD.

PMID- 22149004
TI  - Perfectionism and health: a mediational analysis of the roles of stress, social
      support and health-related behaviours.
AB  - This study tested a model derived from personality theory in which perceived
      stress, perceived social support, health-risk and health-promotion behaviours
      mediate the relationship between perfectionism and perceived physical health. A
      sample of 538 undergraduate students completed a web-based survey assessing multi
      dimensional perfectionism, perceived stress, perceived social support, health
      behaviours, physical health and a scale tapping elements of the five-factor model
      of personality. Analyses that account for the effects of traits from the five
      factor model (e.g., neuroticism, conscientiousness and extraversion) indicated
      that socially prescribed perfectionism was associated with poorer physical health
      and this association was fully mediated by higher levels of perceived stress and
      lower levels of perceived social support. Self-oriented perfectionism was related
      complexly to health such that it was related to poorer health via higher levels
      of perceived stress, but was also related to better health via higher levels of
      perceived social support. Our findings illustrate the need for considering key
      mediators of the link between perfectionism and poor health outcomes.

PMID- 22149005
TI  - Economic evaluation of methadone maintenance treatment in HIV/AIDS control among
      injecting drug users in Dehong, China.
AB  - The purpose of this study was to analyze the cost and cost-effectiveness of
      methadone maintenance treatment (MMT) program in Dehong prefecture, Yunnan
      province, China. The cost-effectiveness analysis used process data
      retrospectively collected from the MMT clinics in Dehong Prefecture, Yunnan
      Province, from July 2005 to December 2007, a 30-month period available at the
      time of the study. Alternative estimates of the number of HIV infections
      prevented were calculated using incidence rate from cohort studies and
      retrospective studies. Program costs were collected retrospectively following
      standard methods using an ingredients methodology. The cost for each participant
      treated in MMT clinics was about $9.1-16.7 per month and the intervention averted
      8.4-87.2 HIV infections with a cost-effectiveness of US$ 2509.3-4609.3 per HIV
      infection averted. This research demonstrates that MMT is a cost-effective
      intervention for reducing HIV transmission among injecting drug users, but the
      coverage of MMT intervention should be matched with the designed volume of MMT
      clinics to make the best use of resources.

PMID- 22149007
TI  - Aggregation kinetics and dissolution of coated silver nanoparticles.
AB  - Determining the fate of manufactured nanomaterials in the environment is
      contingent upon understanding how stabilizing agents influence the stability of
      nanoparticles in aqueous systems. In this study, the aggregation and dissolution
      tendencies of uncoated silver nanoparticles and the same particles coated with
      three common coating agents, trisodium citrate, sodium dodecyl sulfate (SDS), and
      Tween 80 (Tween), were evaluated. Early stage aggregation kinetics of the
      uncoated and coated silver nanoparticles were assessed by dynamic light
      scattering over a range of electrolyte types (NaCl, NaNO(3), and CaCl(2)) and
      concentrations that span those observed in natural waters. Although particle
      dissolution was observed, aggregation of all particle types was still consistent
      with classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The aggregation of
      citrate-coated particles and SDS-coated particles were very similar to that for
      the uncoated particles, as the critical coagulation concentrations (CCC) of the
      particles in different electrolytes were all approximately the same (40 mM NaCl,
      30 mM NaNO(3), and 2 mM CaCl(2)). The Tween-stabilized particles were
      significantly more stable than the other particles, however, and in NaNO(3)
      aggregation was not observed up to an electrolyte concentration of 1 M.
      Differences in the rate of aggregation under diffusion-limited aggregation
      conditions at high electrolyte concentrations for the SDS and Tween-coated
      particles, in combination with the moderation of their electrophoretic
      mobilities, suggest SDS and Tween imparted steric interactions to the particles.
      The dissolution of the silver nanoparticles was inhibited by the SDS and Tween
      coatings, but not by the citrate coating, and in chloride-containing electrolytes
      a secondary precipitate of AgCl was observed bridging the individual particles.
      These results indicate that coating agents could significant influence the fate
      of silver nanoparticles in aquatic systems, and in some cases these stabilizers
      may completely prevent particle aggregation.

PMID- 22149008
TI  - Caffeine alters cytokine secretion by PBMC induced by colon cancer cells.
AB  - BACKGROUND: Studies have shown that caffeine might be capable to prevent colon
      cancer development. This activity is linked in part to its anti-inflammatory
      properties mediated through modulation of immune responses. It was the aim of the
      study to evaluate the role of caffeine in the immune balance between peripheral
      blood mononuclear cells (PBMC) and those of HT-29 and RKO human colon cancer
      lines. METHODS: Cytokine production was evaluated following incubation of the two
      types of cancer cells without and with three concentrations of caffeine. RESULTS:
      A concentration-dependent inhibition of TNFalpha and IFNgamma secretion by PBMC
      was observed only after their stimulation by cancer cells. Reduction of the anti
      inflammatory IL-1ra and IL-10 production was observed using higher caffeine
      concentrations only. CONCLUSION: We presume that by changing the equilibrium
      between pro- and anti-inflammatory cytokines in favor of anti-inflammation,
      caffeine may reduce the inflammatory process with a consequent suppression of
      colorectal cancer progress.

PMID- 22149009
TI  - Regioselective Pd-catalyzed aerobic aza-Wacker cyclization for preparation of
      isoindolinones and isoquinolin-1(2H)-ones.
AB  - A switchable regioselective intramolecular aerobic aza-Wacker cyclization
      catalyzed by palladium is presented. Isoindolinones or isoquinolin-1(2H)-ones
      could be prepared selectively from the same substrates using different catalysts.
      The type and steric hindrance of the ligands may be the variables most
      significant for regiocontrol.

PMID- 22149010
TI  - Screening for depression and anxiety after stroke: developing protocols for use
      in the community.
AB  - PURPOSE: To develop screening protocols to detect depression and anxiety after
      stroke in a community setting and train therapists to administer them. METHOD:
      Psychologists and a community therapist met to design a system suitable for
      screening for anxiety and depression in all those with stroke, including people
      with cognitive and/or communication problems. Other therapists and a local user
      group were also consulted. Therapists were then trained in the use of the
      protocols. The ability to enact the protocols was assessed via case vignettes and
      staff experience, over a month-long trial. RESULTS: It was considered appropriate
      for community therapists to screen patients and to do this within 4 weeks of
      first contact. Two protocols were designed, one for patients without significant
      communication/cognitive deficits and one for patients with these difficulties.
      Therapists applied the protocols with accuracy to the case vignettes and rated
      the training highly. No challenges in applying the protocols in the clinical
      setting were reported over an initial 1-month trial. CONCLUSION: Two protocols to
      screen for depression and anxiety after stroke have been developed. These appear
      feasible for use when trialled via case vignette and in clinical practice.
      Further research might consider the usefulness of the screens in detecting actual
      clinical disorder and developing better screens to identify anxiety after stroke,
      particularly in those with a cognitive and/or communication disorder.

PMID- 22149011
TI  - War, forced displacement and growth in Laotian adults.
AB  - BACKGROUND: Evidence from several populations suggests that war negatively
      impacts civilian nutrition, physical growth and overall health. This effect is
      often enduring or permanent, particularly if experienced early in life. AIM: To
      assess whether the number of lifetime displacement experiences and being
      displaced in infancy were associated with adult height, sitting height, leg
      length and the sitting height ratio. SUBJECTS AND METHODS: Retrospective
      questionnaires on displacement and resettlement experiences and anthropometric
      data were collected from a sample of Laotian adult refugees (ethnic Hmong and
      Lao; n = 365). All were born in Laos or Thailand and had resettled in French
      Guiana or the US. Many had been displaced several times by military conflict in
      Laos. RESULTS: In bivariate analyses, being displaced in infancy and the number
      of lifetime displacement experiences one had were negatively associated with
      final adult height and leg length in both sexes. The association was stronger in
      females, particularly Hmong females. There was no significant association between
      total displacement experiences and the sitting height ratio. In multiple
      regression analyses, linear growth in males was negatively associated with being
      displaced in infancy; in females, the number of lifetime displacement experiences
      was a significant predictor. CONCLUSION: Forced displacement from war appears to
      have a lasting effect on final adult height, sitting height and leg length,
      although not necessarily on the sitting height ratio in this sample.

PMID- 22149012
TI  - The effect of erythropoietin on anastomotic healing of irradiated rats.
AB  - AIM: The aim of the present study is to evaluate the possible protective effects
      of erythropoietin (EPO) on anastomotic wound healing after preoperative
      radiotherapy according to its pleiotropic mechanism of action. METHODS: Thirty
      two male Wistar albino rats were randomized into four groups containing eight
      rats each: ANAS group, standard resection plus anastomosis; RT+ANAS group,
      radiation plus standard resection plus anastomosis; ANAS+EPO group, standard
      resection plus anastomosis plus EPO; RT+ANAS+EPO, radiation plus standard
      resection plus anastomosis plus EPO. All animals were sacrificed by cardiac
      puncture, and anastomotic healing was measured by bursting pressure,
      hydroxyproline (OHP) levels, myeloperoxidase (MPO) activity and histopathological
      evaluations. Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-alpha), and
      matrix metalloproteinase-9 (MMP-9) were also measured in serum specimens.
      RESULTS: OHP levels in the RT+ANAS + EPO group were significantly increased
      compared with other groups (p < .05). In contrast, MPO activity in the
      RT+ANAS+EPO group was significantly decreased compared with other groups (p <
      .05). Serum MDA levels were found to be decreased in the ANAS+EPO and RT+ANAS+EPO
      groups (p < .05). Group comparisons demonstrated that bursting pressure was
      significantly higher in EPO treated rats (p < .05). The histopathology results
      revealed that EPO treatment improves anastomotic wound healing though decreased
      necrosis and inflammatory cell infiltration and increased fibroblast activity.
      CONCLUSION: The findings of the present study indicate that EPO contributes to
      wound healing and the strength of colon anastomosis following radiation due to
      its antioxidant and anti-inflammatory effects, but further studies are needed to
      explore the significance of these effects.

PMID- 22149013
TI  - Medication errors in the obstetrics emergency ward in a low resource setting.
AB  - OBJECTIVE: To investigate the patterns of medication errors in the obstetric
      emergency ward in a low resource setting. MATERIAL AND METHODS: This prospective
      observational study included 10,000 women who presented at the obstetric
      emergency ward, department of Obstetrics and Gynecology, Menofyia University
      Hospital, Egypt between March and December 2010. All medications prescribed in
      the emergency ward were monitored for different types of errors. The head nurse
      in each shift was asked to monitor each pharmacologic order from the moment of
      prescribing till its administration. Retrospective review of the patients' charts
      and nurses' notes was carried out by the authors of this paper. Results were
      tabulated and statistically analyzed. RESULTS: A total of 1976 medication errors
      were detected. Administration errors were the commonest error reported. Omitted
      errors ranked second followed by unauthorized and prescription errors. Three
      administration errors resulted in three Cesareans were performed for fetal
      distress because of wrong doses of oxytocin infusion. The rest of errors did not
      cause patients harm but may have lead to an increase in monitoring. Most errors
      occurred during night shifts. CONCLUSION: The availability of automated infusion
      pumps will probably decrease administration errors significantly. There is a need
      for more obstetricians and nurses during the nightshifts to minimize errors
      resulting from working under stressful conditions.

PMID- 22149015
TI  - When is it appropriate to deliver a prognosis to Korean persons with acute spinal
      cord injury?
AB  - PURPOSE: In cases of complete spinal cord injury (SCI), which has a poor
      probability of recovery, the timely delivery of a prognosis may be crucial to
      help patients adapt to their situation. The study aimed to help for choose the
      appropriate time for delivering a prognosis to persons with SCI. METHOD: Three
      hundred and four members of the Korean SCI Association with complete SCI were
      surveyed regarding the time at which their prognosis was communicated and their
      views about the appropriate time for prognosis delivery. Demographic and injury
      characteristics were also collected. Respondents' experience and opinions on
      prognosis communication were analysed to assess potential associations with
      demographic and injury profiles. RESULTS: Participants' opinions regarding the
      time of prognosis delivery varied. Many respondents (44.1%) reported that the
      appropriate time would be within 1 month postinjury, whereas the others felt it
      should occur either between 1 and 3 months (29.3%) or more than 3 months (10.2%).
      The comparison of time of prognosis communication with the opinions showed that
      most would have preferred an earlier delivery of prognosis than they had
      experienced. CONCLUSIONS: Our findings provide insight to physicians on the
      appropriate time for delivering a prognosis to individuals with complete SCI.

PMID- 22149014
TI  - Gender differences in colorectal cancer incidence in the United States, 1975
      2006.
AB  - BACKGROUND: Gender differences have been documented among patients diagnosed with
      colorectal cancer (CRC). It is still not clear, however, how these differences
      have changed over the past 30 years and if these differences vary by geographic
      areas. We examined trends in CRC incidence between 1975 and 2006. METHODS: The
      study population consisted of 373,956 patients >=40 years diagnosed with
      malignant CRC between 1975 and 2006 who resided in one of the nine Surveillance,
      Epidemiology and End Results (SEER) regions of the United States. Age-adjusted
      incidence rates over time were reported by gender, race, CRC subsite, stage, and
      SEER region. RESULTS: Overall, CRC was diagnosed in roughly equal numbers of men
      (187,973) and women (185,983). Men had significantly higher age-adjusted CRC
      incidence rates across all categories of age, race, tumor subsite, stage, and
      SEER region. Gender differences in CRC age-adjusted incidence rates widened
      slightly from 1975 to 1988, reached a peak in 1985-1988, and have narrowed over
      time since 1990. The largest gap and decline in CRC incidence rates between men
      and women were observed among those >=80 years (p<0.001), followed by those 70-79
      and then 60-69 years. Gender differences in CRC incidence rates for the 40-49 and
      50-59 age categories were small and increased only slightly over time (p=0.003).
      CONCLUSIONS: Higher CRC age-adjusted incidence among men than among women has
      persisted over the past 30 years. Although gender differences narrowed in the
      population >=60 years, especially from 1990 to 2006, gender gaps, albeit small
      ones, in those younger than 60 increased over time. Future studies may need to
      examine the factors associated with these differences and explore ways to narrow
      the gender gap.

PMID- 22149016
TI  - Chitosan microparticles and nanoparticles as biocompatible delivery vehicles for
      peptide and protein-based immunocontraceptive vaccines.
AB  - It has become increasingly recognized that polymer particle size can have a
      profound effect on the interactions of particle-based vaccines with antigen
      presenting cells (APCs) thereby influencing and modulating ensuing immune
      responses. With the aim of developing chitosan particle-based immunocontraceptive
      vaccines, we have compared the use of chitosan-based nanoparticles and chitosan
      based microparticles as vaccine delivery vehicles for vaccine candidates based on
      luteinizing hormone-releasing hormone (LHRH). Particles, functionalized with
      chloroacetyl groups, which allows the covalent attachment of thiol-containing
      antigens, were able to adsorb ~60-70% of their weight of peptide-based antigen
      and 10-20% of their weight of protein-based antigen. Quantitation by amino acid
      analysis of antigen associated with particles demonstrated a correlation between
      associated antigen and the degree of chloracetylation of particles. Visualization
      of fluorescently labeled antigen-loaded particles by confocal microscopy
      indicated that the majority of antigen was localized at the particle surface with
      a smaller amount located in the interior. We also found that uptake of both
      fluoresceinated nanoparticles and microparticles by dendritic cells occurred in a
      manner dependent on particle concentration. Nanoparticles trafficked from the
      injection site to draining lymph nodes faster than microparticles; high numbers
      of nanoparticle-bearing cells appeared in draining lymph nodes on day 3 and
      microparticles on day 4. This difference in trafficking rate did not, however,
      appear to have any significant impact on the ensuing immune response because
      inoculation with both peptide-conjugated and protein-conjugated particles induced
      high levels of LHRH-specific antibodies. In the case of protein-conjugated
      particles, the levels of antibodies elicited were similar to those elicited
      following inoculation with antigen emulsified with complete Freund's adjuvant.
      The approach to vaccine design that we have described here could represent
      another useful method for inducing immune responses against microbial, viral and
      tumorigenic protein antigens.

PMID- 22149017
TI  - Seeing is believing: weak phonon scattering from nanostructures in alkali metal
      doped lead telluride.
AB  - Alkali metal doped p-type PbTe is a canonical thermoelectric material studied
      extensively for heat-to-power generation at high temperature. Most reports have
      indirectly indicated alkali metals to be conventional with PbTe forming
      homogeneous solid solutions. Using transmission electron microscopy (TEM), we
      show the presence of platelet-like nanostructures in these systems containing Na
      and/or K. By combining further TEM and semiclassical theoretical calculations
      based on a modified Debye model of the lattice thermal conductivity, we explain
      the lack of efficacy of these nanostructures for strong phonon scattering. These
      findings are important in the understanding of alkali metals as carriers in p
      type lead chalcogenides. These results also underscore that not all
      nanostructures favorably scatter phonons in a matrix; an insight that may help in
      further improvements of the power factor and the overall figure of merit.

PMID- 22149018
TI  - Risk factors of eclampsia other than hypertension: pregnancy-induced antithrombin
      deficiency and extraordinary weight gain.
AB  - OBJECTIVE: Recent findings suggest that cerebral edema is a characteristic
      finding on magnetic resonance imaging in women with eclampsia and that pregnancy
      induced antithrombin deficiency (PIATD) may reflect enhanced vascular
      permeability and may allow the retention of excess water in the interstitial
      space. Whether PIATD and extraordinary weight gain (EOWG) are risk factors for
      eclampsia remains to be studied. METHODS: The medical records of 11 women with
      eclampsia among 17,522 deliveries were reviewed retrospectively with respect to
      changes in the laboratory data and the maternal body weight. PIATD was defined as
      a perinatal antithrombin activity of <=65% of the normal activity levels with an
      antenatal decline and/or a prompt postnatal increase. A large net weight gain
      during the last two antenatal weeks >97.5th percentile value (>4.01 kg) obtained
      from 272 control women with neither hypertension nor PIATD was defined as EOWG.
      Relative risk was obtained on the assumption that the prevalences of PIATD and
      EOWG were 2.0 and 2.5%, respectively, among 17,511 women who did not develop
      eclampsia. RESULTS: The duration of hypertension until an eclamptic fit was
      within 7 days in all 11 cases. PIATD and EOWG were observed in 6 (54.5%) and 2
      (18.2%) cases, yielding a relative risk (95% confidential interval) of 57.9 (17.7
      188.7) and 8.65 (1.87-39.91) for eclampsia among women with PIATD and EOWG,
      respectively. CONCLUSIONS: PIATD and EOWG may be risk factors for eclampsia.

PMID- 22149023
TI  - Mitochondrial toxicity of antiepileptic drugs and their tolerability in
      mitochondrial disorders.
AB  - INTRODUCTION: Epilepsy is a frequent CNS manifestation of mitochondrial disorders
      (MIDs). At present, patients with MID-related epilepsy are largely treated in the
      same way as any other epilepsy sufferer. The problem with this approach is that
      some antiepileptic drugs (AEDs) are mitochondrial toxic and care is, therefore,
      needed when administering these AEDs to patients with MIDs. AREAS COVERED: This
      review summarizes and discusses the mitochondrial toxicity, tolerability and
      beneficial effects of AED in patients with MIDs. The literature for this article
      was retrieved through PubMed using the search terms: 'mitochondrial disorder',
      'mitochondriopathy', 'mitochondrial', 'cytopathy', 'metabolic disease',
      'epilepsy', 'seizures' and various AEDs alone or in combination. EXPERT OPINION:
      Mitochondrial-toxic AEDs may trigger or worsen an MID or may be even fatal in
      single cases. The AED with the most well-known mitochondrial toxicity is valproic
      acid (VPA), which has been known to exhibit a deleterious effect in patients with
      POLG1 mutations and patients with myoclonic epilepsy with ragged red fibers
      syndrome and VPA should only be applied in MIDs in case of a drug-resistant
      status epilepticus. AEDs other than VPA, which may affect the mitochondrial
      metabolism, include phenobarbital, carbamazepine, phenytoin, oxcarbazepine,
      ethosuximide, zonisamide, topiramate, gabapentin and vigabatrin. AEDs which
      interfere with mitochondrial function should be avoided whenever justifiable to
      the patient's well-being. Collateral beneficial effects of AEDs should also
      influence their choice in MIDs.

PMID- 22149025
TI  - High surface water interaction in superhydrophobic nanostructured silicon
      surfaces: convergence between nanoscopic and macroscopic scale phenomena.
AB  - In the present work, we investigate wetting phenomena on freshly prepared
      nanostructured porous silicon (nPS) with tunable properties. Surface roughness
      and porosity of nPS can be tailored by controlling fabrication current density in
      the range 40-120 mA/cm(2). The length scale of the characteristic surface
      structures that compose nPS allows the application of thermodynamic wettability
      approaches. The high interaction energy between water and surface is determined
      by measuring water contact angle (WCA) hysteresis, which reveals Wenzel wetting
      regime. Moreover, the morphological analysis of the surfaces by atomic force
      microscopy allows predicting WCA from a semiempiric model adapted to this
      material.

PMID- 22149026
TI  - An evaluation of nonclinical dissociation utilizing a virtual environment shows
      enhanced working memory and attention.
AB  - Dissociation is a mental process resulting in the disruption of memory,
      perception, and sometimes identity. At a nonclinical level, only mild
      dissociative experiences occur. The nature of nonclinical dissociation is
      disputed in the literature, with some asserting that it is a beneficial
      information processing style and others positing that it is a psychopathological
      phenomenon. The purpose of this study was to further the understanding of
      nonclinical dissociation with respect to memory and attention, by including a
      more ecologically valid virtual reality (VR) memory task along with standard
      neuropsychological tasks. Forty-five undergraduate students from a small liberal
      arts college in the northeast participated for course credit. The participants
      completed a battery of tasks including two standard memory tasks, a standard
      attention task, and an experimental VR memory task; the VR task included
      immersion in a virtual apartment, followed by incidental object-location recall
      for objects in the virtual apartment. Support for the theoretical model
      portraying nonclinical dissociation as a beneficial information processing style
      was found in this study. Dissociation scores were positively correlated with
      working memory scores and attentional processing scores on the standard
      neuropsychological tasks. In terms of the VR task, dissociation scores were
      positively correlated with more false positive memories that could be the result
      of a tendency of nonclinical highly dissociative individuals to create more
      elaborative schemas. This study also demonstrates that VR paradigms add to the
      prediction of cognitive functioning in testing protocols using standard
      neuropsychological tests, while simultaneously increasing ecological validity.

PMID- 22149024
TI  - Human proteome-scale structural modeling of E2-E3 interactions exploiting
      interface motifs.
AB  - Ubiquitination is crucial for many cellular processes such as protein
      degradation, DNA repair, transcription regulation, and cell signaling. Ubiquitin
      attachment takes place via a sequential enzymatic cascade involving ubiquitin
      activation (by E1 enzymes), ubiquitin conjugation (by E2 enzymes), and ubiquitin
      substrate tagging (by E3 enzymes). E3 ligases mediate ubiquitin transfer from E2s
      to substrates and as such confer substrate specificity. Although E3s can interact
      and function with numerous E2s, it is still unclear how they choose which E2 to
      use. Identifying all E2 partners of an E3 is essential for inferring the
      principles guiding E2 selection by an E3. Here we model the interactions of E3
      and E2 proteins in a large, proteome-scale strategy based on interface structural
      motifs, which allows elucidation of (1) which E3s interact with which E2s in the
      human ubiquitination pathway and (2) how they interact with each other. Interface
      analysis of E2-E3 complexes reveals that loop L1 of E2s is critical for binding;
      the residue in the sixth position in loop L1 is widely utilized as an interface
      hot spot and appears indispensible for E2 interactions. Other loop L1 residues
      also confer specificity on the E2-E3 interactions: HECT E3s are in contact with
      the residue in the second position in loop L1 of E2s, but this is not the case
      for the RING finger type E3s. Our modeled E2-E3 complexes illuminate how slight
      sequence variations in E2 residues may contribute to specificity in E3 binding.
      These findings may be important for discovering drug candidates targeting E3s,
      which have been implicated in many diseases.

PMID- 22149027
TI  - Oncolytic viruses: smart therapeutics for smart cancers.

PMID- 22149028
TI  - Combating angiogenesis early: potential of targeting tumor-recruited neutrophils
      in cancer therapy.

PMID- 22149030
TI  - The European Multidisciplinary Cancer Congress (ECCO 16, ESMO 36 and ESTRO 30).
AB  - "Integrating basic and translational science, surgery, radiotherapy, medical
      oncology, and care" was the mission statement of the 2011 European
      Multidisciplinary Cancer Congress, which was held in Stockholm, Sweden, on 23-27
      September 2011.

PMID- 22149031
TI  - Integration of adenovirus thymidine kinase suicide-gene therapy with surgery and
      radiation therapy for malignant glioma.
AB  - Evaluation of: Chiocca EA, Aguilar LK, Bell SD et al. Phase IB study of gene
      mediated cytotoxic immunotherapy adjuvant to up-front surgery and intensive
      timing radiation for malignant glioma. J. Clin. Oncol. 29(27), 3611-3619 (2011).
      This report of a clinical Phase IB trial uses adenoviral vectors injected in a
      dose escalation manner during surgical excision of primary gliomas to express
      thymidine kinase and activate the prodrugvalacyclovir, which is administered so
      as to overlap in part with a standard radiation therapy schedule. The approach
      aimed to exploit several mechanisms associated with this form of gene therapy,
      namely tumor cell suicide, radiosensitization and the antitumor immunotherapeutic
      response that it can activate. The most novel aspect of the trial was the early
      start to radiation therapy 1 week after surgery that was designed to allow for
      radiosensitization by orally administered valacyclovir. In general, the treatment
      was well tolerated and the overall median survival for patients was 12.4 months
      with a 3-year survival of 25%. There was evidence of immune cell infiltration in
      all four resection specimens that were examined but no sign of an importance to
      viral dose within the range of 3 * 10(10)-3 * 10(11) particles. This was a small
      trial with only 13 patients but the results warrant the initiation of further
      clinical trials to investigate what is now a fairly old but still promising
      strategy.

PMID- 22149032
TI  - Liver tumor models in transgenic zebrafish: an alternative in vivo approach to
      study hepatocarcinogenes.
AB  - The small vertebrate, zebrafish, has generated a big wave in current biomedical
      research. In the early experiments of carcinogen treatment, it has been found
      that the induced tumors in the zebrafish share many similar features with those
      of humans. With the recent development in transgenic technology, we are able to
      control the expression of a specific oncogene in targeted organs for generation
      of different tissue tumor models in zebrafish. In particular, the fusion of an
      oncogene and a color reporter, such as the green fluorescent protein, allows us
      to conveniently monitor transgenic tumors for their initiation, progression,
      metastasis and transplantation in the transparent zebrafish embryos, as
      demonstrated in this article with our newly established liver cancer models. What
      does the future hold in this rapidly growing model organism? Other than
      understanding the molecular mechanisms of carcinogenesis, one obvious area will
      be the potential of these models for rapid and high-throughput screening for
      anticancer drugs.

PMID- 22149033
TI  - Cancer permeates locally within ontogenetic compartments: clinical evidence and
      implications for cancer surgery.
AB  - The pathophysiologic process of local tumor spread is regarded as an isotropic
      infiltration of microscopic extensions of the malignant lesion irrespective of
      tissue boundaries. By contrast, the ontogenetic compartment theory states that
      malignant solid tumors are locally confined, for a relatively long phase during
      their natural course, to a permissive compartment derived from a common
      primordium in embryonic development. Tumor permeation is isotropic within the
      permissive ontogenetic compartment, but it is suppressed at the compartment
      borders. The validity of the ontogenetic compartment theory has been shown for
      cancer of the rectum and of the female lower genital tract. It is hypothesized
      that ontogenetic compartment resection, the translation of the theory into cancer
      surgery, holds a great potential to improve oncologic treatment results.

PMID- 22149034
TI  - Comparative effectiveness research for prostate cancer radiation therapy: current
      status and future directions.
AB  - Comparative effectiveness research aims to help clinicians, patients and
      policymakers make informed treatment decisions under real-world conditions.
      Prostate cancer patients have multiple treatment options, including active
      surveillance, androgen deprivation therapy, surgery and multiple modalities of
      radiation therapy. Technological innovations in radiation therapy for prostate
      cancer have been rapidly adopted into clinical practice despite relatively
      limited evidence for effectiveness showing the benefit for one modality over
      another. Comparative effectiveness research has become an essential component of
      prostate cancer research to help define the benefits, risks and effectiveness of
      the different radiation therapy modalities currently in use for prostate cancer
      treatment.

PMID- 22149036
TI  - Cancer therapy with trifunctional antibodies: linking innate and adaptive
      immunity.
AB  - Trifunctional antibodies (trAbs) are promising novel anticancer biologics with a
      particular mode of action capable of linking innate with adaptive immunity. Based
      on their unique structure, trifunctional IgG-like heterodimeric antibodies,
      consisting of nonhuman mouse and rat immunoglobulin halves are able to redirect T
      lymphocytes, as well as accessory cells, to the tumor site. This recruitment of
      immune cells is accompanied by cellular activation events elicited by anti-CD3,
      as well as Fcgamma-receptor engagement of trAbs supported by a proinflammatory
      Th1-biased cytokine milieu. All necessary immunological factors required for long
      term vaccination-like effects are stimulated along trAb-mediated therapeutic
      interventions. Thus, the concerted interplay of antibody-dependent cellular
      cytotoxicity plus the polyclonal T-cell cytotoxicity and Fcgamma-receptor-driven
      induction of long-lasting immune responses after the initial tumor cell
      elimination represent the major hallmarks of trAb-mediated treatment of malignant
      diseases.

PMID- 22149037
TI  - Improving the outcomes: developing cancer therapeutics.
AB  - Oncology therapeutics are less likely to reach the market than other
      therapeutics, at a higher cost, and only approximately one in ten cancer drugs in
      clinical development actually reach the market. To improve, there need to be new
      approaches to oncology research and development, based on understanding cancer
      biology and improving preclinical models and clinical trials, such as more use of
      biomarkers and evaluation of other targets including cancer stem cells and use of
      combination therapies. Biomarkers can be used to make early go/no-go decisions in
      drug development and can speed up drug development by selecting patients who will
      benefit and excluding patients likely to experience severe side effects, but they
      need validation before use. New approaches to preclinical and clinical trials can
      also speed up and improve the development of cancer therapeutics.

PMID- 22149038
TI  - Primary non-Hodgkin's lymphoma of the breast: mammography, ultrasound, MRI and
      pathologic findings.
AB  - Primary non-Hodgkin's lymphoma of the breast (PBNHL) is uncommon. There have been
      only a few reports of breast lymphoma in the radiology literature. In this case
      report, we describe mammographic, sonographic and MRI findings, in addition to
      surgical and histopathologic findings, in a patient with PBNHL. In particular,
      the diffusion-weighted imaging sequence of MRI in a patient with PBNHL has yet to
      be reported in the published literature. Mammographic and sonographic imaging
      findings are limited in the diagnosis of this rare disease. MRI may play an
      important role in the assessment of multicentric lesions and staging of mammary
      malignancies preoperation. MRI may also be useful in the follow-up of breast
      lymphoma patients to monitor response to chemotherapy and radiotherapy and to
      diagnose disease recurrence.

PMID- 22149040
TI  - Introduction to special section of the Journal of Family Psychology, advances in
      mixed methods in family psychology: integrative and applied solutions for family
      science.
AB  - Mixed methods in family psychology refer to the systematic integration of
      qualitative and quantitative techniques to represent family processes and
      settings. Over the past decade, significant advances have been made in study
      design, analytic strategies, and technological support (such as software) that
      allow for the integration of quantitative and qualitative methods and for making
      appropriate inferences from mixed methods. This special section of the Journal of
      Family Psychology illustrates how mixed methods may be used to advance knowledge
      in family science through identifying important cultural differences in family
      structure, beliefs, and practices, and revealing patterns of family relationships
      to generate new measurement paradigms and inform clinical practice. Guidance is
      offered to advance mixed methods research in family psychology through sound
      principles of peer review.

PMID- 22149035
TI  - Protein biomarkers of ovarian cancer: the forest and the trees.
AB  - The goal of effective population-based screening for ovarian cancer remains
      elusive despite intense efforts aimed at improving upon biomarker and imaging
      modalities. While dozens of potential serum biomarkers for ovarian cancer have
      been identified in recent years, none have yet overcome the limitations that have
      hindered the clinical use of CA-125. Avenues of opportunity in biomarker
      development are emerging as investigators are beginning to appreciate the
      significance of remote, as well as local or regional, sources of biomarkers in
      the construction of diagnostic panels, as well as the importance of evaluating
      biomarkers in prediagnostic settings. As the list of candidate biomarkers of
      ovarian cancer continues to grow, refinements in the methods through which
      specific proteins are selected for further development as components of
      diagnostic panels are desperately sought. Such refinements must take into account
      both the bioinformatic and biological significance of each candidate. Approaches
      incorporating these considerations may potentially overcome the challenges to
      early detection posed by the histological heterogeneity of ovarian cancer. Here,
      we review the recent progress achieved in efforts to develop diagnostic biomarker
      panels for ovarian cancer and discuss the challenges that remain.

PMID- 22149041
TI  - Children's activities and their meanings for parents: a mixed-methods study in
      six Western cultures.
AB  - Theoretical perspectives and research in sociology, anthropology,
      sociolinguistics, and cultural psychology converge in recognizing the
      significance of children's time spent in various activities, especially in the
      family context. Knowing how children's time is deployed, however, only gives us a
      partial answer to how children acquire competence; the other part must take into
      account the culturally constructed meanings of activities, from the perspective
      of those who organize and direct children's daily lives. In this article, we
      report on a study of children's routine daily activities and on the meanings that
      parents attribute to them in six Western middle-class cultural communities
      located in Italy, The Netherlands, Poland, Spain, Sweden, and the United States
      (N = 183). Using week-long time diaries kept by parents, we first demonstrate
      similarities as well as significant differences in children's daily routines
      across the cultural samples. We then present brief vignettes--"a day in the life"
      --of children from each sample. Parent interviews were coded for themes in the
      meanings attributed to various activities. Excerpts from parent interviews,
      focusing on four major activities (meals, family time, play, school- or
      developmentally related activities), are presented to illustrate how cultural
      meanings and themes are woven into parents' organization and understanding of
      their children's daily lives. The results of this mixed-method approach provide a
      more reliable and nuanced picture of children's and families' daily lives than
      could be derived from either method alone.

PMID- 22149042
TI  - "Holler, run, be loud:" strategies for promoting child physical activity in a low
      income, African American neighborhood.
AB  - This article identifies and describes child management practices among a sample
      of African American caregivers in a low-income, inner-city neighborhood.
      Caregivers responded to low levels of neighborhood collective socialization,
      collective efficacy, social control, and institutional resources by using
      strategies that protected children and promoted physical activity. Using diverse
      qualitative methods (interviews, observations) and demographic data on
      neighborhood disadvantage and family and household characteristics, the research
      revealed seven caregiver management strategies that promoted child physical
      activity, despite multiple neighborhood barriers. These included ecological
      appraisal, boundary enforcement, chaperonage, kin-based play groups, collective
      supervision, local resource brokering, and extralocal resource brokering. These
      findings provide important substantive and theoretical insights on the
      relationship between caregiver practices, neighborhood social context, and child
      physical activity.

PMID- 22149043
TI  - An approximate model for cancellous bone screw fixation.
AB  - This paper presents a finite element (FE) model to identify parameters that
      affect the performance of an improved cancellous bone screw fixation technique,
      and hence potentially improve fracture treatment. In cancellous bone of low
      apparent density, it can be difficult to achieve adequate screw fixation and
      hence provide stable fracture fixation that enables bone healing. Data from
      predictive FE models indicate that cements can have a significant potential to
      improve screw holding power in cancellous bone. These FE models are used to
      demonstrate the key parameters that determine pull-out strength in a variety of
      screw, bone and cement set-ups, and to compare the effectiveness of different
      configurations. The paper concludes that significant advantages, up to an order
      of magnitude, in screw pull-out strength in cancellous bone might be gained by
      the appropriate use of a currently approved calcium phosphate cement.

PMID- 22149044
TI  - Developing and piloting an expert system for better routine voluntary HIV
      counseling and testing in China: preliminary results and lessons.
AB  - This study aims at developing and testing a pragmatic expert system for HIV
      voluntary counseling (VCT-ES) that leverages best practices. The VCT-ES was
      developed via evolutionary prototyping and piloted in 10 voluntary HIV counseling
      and testing (VCT) clinics from Anhui and Beijing representative of prefecture and
      county level VCT clinics in China. All counselors with the clinics and the
      clients to the clinics within selected two weeks at baseline and the end of study
      were invited to participate. Assessment measures included essential counseling
      procedures (ECPs); clients' satisfaction, knowledge, and behavior efficacy. VCT
      ES was developed which tries to model and facilitate standard VCT operation
      procedures and best practices. One hundred and eighty-two (96 at baseline vs. 86
      after intervention) cases recordings, 172 (96 vs. 76) client questionnaires, 10
      counselor, and 2 expert rating instruments were collected; and 17 clients and 8
      counselors participated in qualitative interviews. VCT-ES increased delivery of
      ECPs from 18.94% to 66.39% on average; increased clients' knowledge from 40.51%
      to 86.34% and self-efficacy by 22.42%. The VCT-ES applications listed were rated
      9.1 on average (maximum = 10). The VCT-ES could be an easy and effective solution
      to better routine VCT and merits further research.

PMID- 22149045
TI  - Testicular toxicity of para-phenylenediamine after subchronic topical application
      in rat.
AB  - Para-phenylenediamine (PPD) is a most widely used chemical in almost all hair dye
      formulations. The present experiment was conducted in order to assess the
      reproductive toxicity of PPD in male rats. After sub-chronic topical application
      of different doses (0, 1, 2 and 3 mg/kg/day) of PPD, the male albino rats
      exhibited significant decrease in the total sperm count (p<0.05, 0.01) with
      consistent decrease in the testicular weight (p<0.05), increase in the germ cell
      apoptosis indicated by cellular morphology as well as loss of germinal layer,
      sloughing of testicular cellular layers. Elevation of lipid peroxidation product
      in the testicular tissue indicated the potential oxidative stress that may be
      crucial in the induction of the apoptosis and further tissue injury in the PPD
      treated rats. The study was designed to examine the testicular effect of 1% to 3%
      PPD which mimic the actual dosage available in most of the hair dying
      formulation. The possibilities of impaired testicular function after sub-chronic
      topical exposure to PPD on male rats have demonstrated.

PMID- 22149046
TI  - Tracking living decapod larvae: mass staining of eggs with neutral red prior to
      hatching.
AB  - Mass staining of decapod females carrying eggs, with subsequent identification of
      hatched larvae in the environment, is a research tool with great potential for
      field ecologists wishing to track the movements of larvae. For this to be
      achieved, however, numerous requirements must be met. These include adequate dye
      solubility, short staining time, dye penetration through different tissues, dye
      retention within the organism, absence of toxic and behavioral effects, low
      visibility to predators of stained larvae, no loss of staining owing to
      preservatives and low cost. The dye, neutral red, appears to meet most of these
      requirements. This dye was used in aliquots of 0.7 g/770 ml seawater applied to
      the females of Norway lobster (Nephrops norvegicus) and European lobster (Homarus
      gammarus) for 10 min. This procedure stained lobster eggs and embryos so that
      hatched larvae could be distinguished easily by fluorescence microscopy from
      larvae that hatched from unstained eggs. Stained larvae that were preserved in 4%
      formaldehyde in seawater were still stained after 1 year. Larvae should not come
      in contact with ethanol, because it extracts the dye rapidly.

PMID- 22149047
TI  - Testing integrated behavioural and biomedical models of activity and activity
      limitations in a population-based sample.
AB  - PURPOSE: The predictive utility of an integrated model of disability is tested.
      The integrated model incorporates an impairment based model (International
      Classification of Functioning, Disability and Health (ICF)) and the behavioural
      models. METHODS: Community dwelling adults (n = 628) completed a postal
      questionnaire measuring the integrated model. The ability of the model to predict
      disability in the form of activity limitations (ALs) and walking, in the full
      community sample and in respondents reporting chronic pain was tested. RESULTS:
      In both the community and chronic pain samples each version of the integrated
      model explained a majority (55%-67%) of the variance in ALs but only 11%-29% of
      the variance in walking behaviour (WB). Impairment directly predicted ALs but did
      not directly predict WB. Control related cognitions were direct predictors, and
      mediators, of the relationship between bodily impairment and both ALs and WB. In
      addition, intentions and outcome expectancies predicted WB. Self-efficacy (SE)
      was the most consistent predictor of both ALs and WB. CONCLUSIONS: An integrated
      model which combines psychological constructs and impairment is required for an
      adequate understanding of ALs. By contrast, behavioural models, but not degree of
      impairment, are necessary to explain activity levels.

PMID- 22149048
TI  - Selective oxoammonium salt oxidations of alcohols to aldehydes and aldehydes to
      carboxylic acids.
AB  - The oxidation of alcohols to aldehydes using stoichiometric 4-acetamido-2,2,6,6
      tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH(2)Cl(2) at room
      temperature is a highly selective process favoring reaction at the carbinol
      center best able to accommodate a positive charge. The oxidation of aldehydes to
      carboxylic acids by 1 in wet acetonitrile is also selective; the rate of the
      process correlates with the concentration of aldehyde hydrate. A convenient and
      high yield method for oxidation of alcohols directly to carboxylic acids has been
      developed.

PMID- 22149058
TI  - Serum profiling to distinguish early- and late-stage ovarian cancer patients from
      disease-free individuals.
AB  - Sera mass spectrometry (MS) peak differences were analyzed from 35 ovarian cancer
      patients and 16 disease-free individuals. "Leave one out" cross validation was
      used to assign "% cancer peaks" in control and ovarian cancer sera samples. Sera
      MS discriminated stage I/II and stage III/V ovarian cancer patients versus
      controls with ROC curve area values of 0.82 and 0.92. Test sensitivities for
      ovarian cancer stage I/II and III/V were 80% and 93% respectively. These results
      indicate that MS is useful for distinguishing sera from early-stage ovarian
      cancer patients, and has potential as a test for early detection of this disease.

PMID- 22149059
TI  - Prevalence of metabolic syndrome and related metabolic traits in an island
      population of the Adriatic.
AB  - BACKGROUND: Metabolic syndrome, a constellation of risk factors associated with
      cardiovascular disease and Type 2 diabetes, has reached epidemic proportions
      worldwide. Epidemiological studies in transitional societies will provide insight
      into the underlying factors that interact in its manifestation. AIMS: To estimate
      the prevalence of metabolic syndrome, provide a comparative analysis of two
      metabolic syndrome definitions and assess clustering and association of metabolic
      traits and cardiovascular diseases in an Adriatic island population. SUBJECTS AND
      METHODS: In a cross-sectional study, data on four anthropometric, blood pressure
      and 11 biochemical traits were obtained from 1430 adults from the island of Hvar.
      RESULTS: Prevalence of metabolic syndrome was 25% and 38.5% based on Adult
      Treatment Panel III and International Diabetes Federation definitions,
      respectively. Rates of abdominal obesity, elevated blood glucose and hypertension
      were high. Among the traits not included in the definitions, levels of LDL, total
      cholesterol and fibrinogen were markedly elevated. The majority of the phenotypes
      were significantly associated with the syndrome, the strongest being waist
      circumference. CONCLUSION: The Croatian islanders are characterized by a high
      prevalence of metabolic abnormalities. Central obesity is the strongest
      contributor of the syndrome. With a high prevalence of dyslipidemia and pro
      inflammatory factors, the population is at substantial risk for cardiovascular
      diseases.

PMID- 22149060
TI  - A longitudinal study of patients' experiences of chronic low back pain using
      interpretative phenomenological analysis: changes and consistencies.
AB  - This paper present data from the second and third rounds of a three-phase
      longitudinal research project exploring the 'lived experiences' of patients with
      chronic low-back pain (CLBP) in the United Kingdom. Qualitative, semi-structured
      interviews were conducted with eight participants 1 and 2 years after the first
      interviews and after attendance at a medically staffed chronic pain clinic. The
      transcribed accounts were analysed using interpretative phenomenological analysis
      and results compared with the data from time one. A main challenge for
      participants was managing constant unchanging pain experiences and loss across
      all areas of their lives. Some participants held consistent biomedical
      understandings of CLBP, continued to focus on the physicality of their pain and
      adopt a narrow range of behavioural-focused coping strategies and maintained a
      strong loss orientation. It is proposed that these elements demonstrated embodied
      experiences and contributed to comprehensive enmeshment of self and pain with
      little re-establishment of any behavioural activity. In comparison, participants
      who had experienced pain relief due to physical treatments showed increased use
      of mind-body strategies, a future orientation and were considered to be less
      enmeshed in their experiences. These changes were discussed in relation to the
      relationship between pain remission and illness beliefs.

PMID- 22149061
TI  - Solar Cell light trapping beyond the ray optic limit.
AB  - In 1982, Yablonovitch proposed a thermodynamic limit on light trapping within
      homogeneous semiconductor slabs, which implied a minimum thickness needed to
      fully absorb the solar spectrum. However, this limit is valid for geometrical
      optics but not for a new generation of subwavelength solar absorbers such as
      ultrathin or inhomogeneously structured cells, wire-based cells, photonic crystal
      based cells, and plasmonic cells. Here we show that the key to exceeding the
      conventional ray optic or so-called ergodic light trapping limit is in designing
      an elevated local density of optical states (LDOS) for the absorber. Moreover,
      for any semiconductor we show that it is always possible to exceed the ray optic
      light trapping limit and use these principles to design a number of new solar
      absorbers with the key feature of having an elevated LDOS within the absorbing
      region of the device, opening new avenues for solar cell design and cost
      reduction.

PMID- 22149062
TI  - Transport of topical anesthetics in vitamin E loaded silicone hydrogel contact
      lenses.
AB  - Transport of surface active anesthetic drugs through silicone hydrogel contact
      lenses containing nanosized vitamin E aggregates is explored for achieving
      extended anesthetics delivery. Commercial silicone hydrogel contact lenses
      release most ophthalmic drugs including local anesthetics for only a few hours,
      which is not adequate. Here we focus on creating dispersion of highly hydrophobic
      vitamin E aggregates in the lenses as barriers for drug diffusion for increasing
      the release durations. This approach has been shown previously to be successful
      in extending the release durations for some common hydrophilic ophthalmic drugs.
      The topical anesthetic drugs considered here (lidocaine, bupivacaine, and
      tetracaine) are hydrophilic at physiologic pH due to the charge, and so these
      cannot partition into the vitamin E barriers. However, these surface active drug
      molecules adsorb on the surface of the vitamin E barriers and diffuse along the
      surface, leading to only a small decrease in the effective diffusivity compared
      to non-surface-active hydrophilic drugs. The drug adsorption can be described by
      the Langmuir isotherm, and measurements of surface coverage of the drugs on the
      vitamin E provide an estimate of the available surface area of vitamin E, which
      can then be utilized to estimate the size of the aggregates. A diffusion
      controlled transport model that includes surface diffusion along the vitamin E
      aggregates and diffusion in the gel fit the transport data well. In conclusion,
      the vitamin E loaded silicone contact lens can provide continuous anesthetics
      release for about 1-7 days, depending on the method of drug loading in the
      lenses, and thus could be very useful for postoperative pain control after
      corneal surgery such as the photorefractive keratectomy (PRK) procedure for
      vision correction.

PMID- 22149063
TI  - Effects of inhaled inactivated Mycobacterium phlei on airway inflammation in
      mouse asthmatic models.
AB  - BACKGROUND: Corticosteroids are the most efficacious anti-inflammatory drugs for
      asthma therapy; however, steroids are not always completedly effective for
      asthma. Studies have shown Mycobacterium bovis Bacille Calmette-Guerin (BCG) and
      other mycobacterial infections suppress airway hyperresponsiveness and
      inflammation in asthma. We use a murine model of Ovalbumin (OVA)-induced asthma
      to study whether nebulized inhalation of inactivated Mycobacterium phlei can
      alleviate asthmatic airway inflammation through influencing cytokine production
      and determine whether it can prevent and treat asthma. METHODS: Fifth male Balb/c
      mice were randomly divided into four groups: normal control group (A), asthma
      model group (B0, B3, B4, B5), the treatment group (C0, C3, C4, C5), and
      prevention group (D). Mice were sensitizated and challenged with Ovalbumin to
      make a murine asthma model. Group C were given treatment of aerosol Mycobacterium
      phlei once daily after OVA challenge. Groups C3, C4, and C5 were treated for 3
      days, 4 days, and 5 days, respectively. Group D inhaled the solution of
      inactivated Mycobacterium phlei daily before each time of OVA challenge. All the
      animals were killed and lung tissue and bronchoalveolar lavage fluid (BALF) were
      harvested. Pathological HE staining and AB-PAS staining were done to measure lung
      inflammation and mucus production. Total cell numbers and differential cell count
      in BALF were performed. Cytokines IL-4, IL-10, and IFN-gamma levels in BALF were
      quantified by ELISA. RESULTS: In groups C4, C5, and D, IL-4 production in BALF
      was decreased and IL-10 and IFN-gamma were increased (p<0.05).The number of total
      inflammatory cells and the mean percentage of eosinophils and lymphocytes in the
      BALF of group D, group C4, and group C5 was lower than in the corresponding group
      B (p<0.05). Histological examination of the lungs showed airway inflammation of
      group D and group C5 were attenuated. CONCLUSION: The inhalation of Mycobacterium
      phlei can reduce airway inflammation in asthmatic mice. This ability was
      associated with its immunomodulatory effect on regulating IL-4, IL-10, and IFN
      gamma secretion. Aerosol administration of inactivated Mycobacterium phlei may be
      accepted as an alternative method with less risk of adverse reactions in
      treatment of asthma.

PMID- 22149064
TI  - Oligoclonal antibody targeting ghrelin increases energy expenditure and reduces
      food intake in fasted mice.
AB  - Ghrelin, an enteric peptide hormone linked to the pathophysiology of obesity has
      been a therapeutic target of great interest over the past decade. Many research
      efforts have focused on the antagonism of ghrelin's endogenous receptor GHSR1a,
      which is found along ascending vagal afferent fibers, as well as in the arcuate
      nucleus of the hypothalamus. Additionally, peptidic inhibitors of ghrelin O
      acyltransferase, the enzyme responsible for the paracrine activation of ghrelin,
      have recently been studied. Our research has taken an alternative immunological
      approach, studying both active and passive vaccination as a means to sequester
      ghrelin in the periphery, with the original discovery in rat of decreased feed
      efficiency and adiposity, as well as increased metabolic activity. Using our
      previous hapten designs as a stepping-stone, three monoclonal antibodies (JG2,
      JG3, and JG4) were procured against ghrelin and tested in vivo. While mAb JG4 had
      the highest affinity for ghrelin, it failed to attenuate the orexigenic effects
      of food deprivation on energy metabolism or food intake in mice. However, animals
      that were administered a combination of JG3:JG4 (termed a doublet) or JG2:JG3:JG4
      (termed a triplet) demonstrated higher heat dispersion and rate of respiration
      (higher CO(2) emission and O(2) consumption) during a 24 h fast refeed. Mice
      administered the triplet cocktail of JG2:JG3:JG4 also demonstrated decreased food
      intake upon refeeding as compared to control animals. Recently, Lu and colleagues
      reported that a passive approach using a single, high affinity N-terminally
      directed monoclonal antibody did not abrogate the effects of endogenous ghrelin.
      Our current report corroborates this finding, yet, refutes that a monoclonal
      antibody approach cannot be efficacious. Rather, we find that a multiple
      monoclonal antibody (oligoclonal) approach can reproduce the underlying logic to
      previously reported efficacies using active vaccinations.

PMID- 22149066
TI  - The role of health economics in alcohol policy.

PMID- 22149065
TI  - Effects of vitamin D3 and calcium supplementation on serum levels of tocopherols,
      retinol, and specific vitamin D metabolites.
AB  - gamma-Tocopherol (gammaT) protects against DNA-damaging effects of nitrogen
      oxides, yet its physiologic regulation in vivo is unknown. Observational studies
      indicate inverse associations of 25[OH]-vitamin D with gammaT and leptin. To
      determine whether vitamin D(3) supplementation alters levels of lipid-soluble
      micronutrients, serum samples (N = 85 subjects) from a randomized, double-blind,
      placebo-controlled clinical trial of vitamin D(3) (800 IU) and calcium (2 g),
      alone and in combination, were analyzed for lipid micronutrients and specific
      vitamin D metabolites at baseline and after 6 mo of supplementation. Serum 25[OH]
      vitamin D(3) levels increased 55% (P < 0.0001) and 48% (P = 0.0005), whereas
      25[OH]-vitamin D(2) levels were lower by 48% (P = 0.26) and 21% (P = 0.36) in the
      vitamin D(3) and vitamin D(3) plus calcium groups, respectively. At baseline,
      gammaT levels were inversely associated with 25[OH]D (r = -0.31, P = 0.004). With
      vitamin D(3) plus calcium treatment, serum alpha-tocopherol decreased 14% (P =
      0.04), whereas similar changes in gammaT (19% lower, P = 0.14) were observed. No
      significant effects were observed for D(3) supplementation on leptin or retinol
      levels. These results are consistent with the hypothesis that vitamin D(3) +/-
      calcium affects serum tocopherol and 25[OH]D(2) levels; however, studies using
      larger, more homogeneous populations are warranted.

PMID- 22149067
TI  - The ProFitMap-neck--reliability and validity of a questionnaire for measuring
      symptoms and functional limitations in neck pain.
AB  - PURPOSE: To assess overall reliability and validity of a neck-specific
      questionnaire, the Profile Fitness Mapping neck questionnaire (ProFitMap-neck),
      on three chronic neck pain groups. METHOD: Participating groups were as follows:
      whiplash associated disorders, inpatient care (IP-WAD, n=127); nonspecific neck
      pain, inpatient care (IP-NS, n=83) and nonspecific neck pain subjects (non-IP-NS,
      n=104). All groups answered the ProFitMap-neck and the SF-36, whereas non-IP-NS
      also answered the Neck Disability Index (NDI) and the Functional Self-Efficacy
      Scale (SES). Internal consistency, test-retest reliability and components of
      convergent construct, face and content validity were determined for the ProFitMap
      neck. RESULTS: The ProFitMap-neck showed good internal consistency in all three
      groups, and ICC test-retest reliability (0.80-0.91). Good correlation (0.66-0.78)
      and highest agreement was reached with NDI. According to the International
      Classification of Functioning, Disability and Health, the symptom scale of the
      ProFitMap-neck was mainly classified to the domain of impairments-body functions,
      and the functional limitation scale to the activity limitation domain.
      CONCLUSION: The results indicate that the ProFitMap-neck is valid for measuring
      symptoms and functional limitations in people with chronic neck pain. The
      combination of a composite total score of symptoms and function as well as
      separate scores of each domain makes ProFitMap-neck suitable for research as well
      as in clinical practice.

PMID- 22149072
TI  - Ocular motor dysfunction in Parry-Romberg syndrome: four cases.
AB  - The authors describe four patients with Parry-Romberg syndrome (PRS) who had
      abnormal eye movements, ptosis, and facial hemiatrophy. There were delays in
      diagnosis in all cases, often requiring multiple imaging studies, prior to
      diagnosis of PRS. These cases demonstrate the variable ophthalmic manifestations
      of PRS, which can lead to difficulty in diagnosis. Case 1 was a 23-year-old woman
      with lateral rectus paresis who presented with horizontal diplopia and developed
      ptosis and facial hemiatrophy. Case 2 was a 28-year-old woman with medial rectus
      weakness adjusted to diplopia by head turn and gaze preference. Case 3 was a 68
      year-old woman who presented with dry eye symptoms and was noted to prefer right
      gaze and have left hemifacial atrophy. Case 4 was a 68-year-old woman who
      presented with ptosis, enophthalmos, and restriction of up gaze. The ocular motor
      defect in all of these cases is best explained by muscle fibrosis rather than
      nerve paresis.

PMID- 22149073
TI  - Progressive growth of bilateral choroidal osteomas in a child.
AB  - A 7-year-old girl was referred for retinal dystrophy. On examination, visual
      acuity was 20/20 in the right eye and 20/30 in the left eye. Fundus examination
      revealed bilateral orange-colored subfoveal choroidal tumors. Ultrasonography
      showed calcification, confirming the diagnosis of choroidal osteoma. Because
      vision was preserved without subretinal fluid or choroidal neovascularization,
      observation with calcium supplementation was recommended. Three years later,
      there was minimal tumor growth and visual acuity was maintained. Choroidal
      osteomas are rare, benign tumors that may decrease vision through
      decalcification, particularly when subfoveal. In these cases, cautious
      observation and possibly calcium supplementation may help protect vision.

PMID- 22149074
TI  - X-ray irradiation as a microbial intervention strategy for food.
AB  - First recognized in 1895, X-ray irradiation soon became a breakthrough diagnostic
      tool for the dental and medical professions. However, the food industry remained
      slow to adopt X-ray irradiation as a means for controlling insects and microbial
      contaminants in food, instead using gamma and electron beam (E-beam) irradiation.
      However, the reinvention of X-ray machines with increased efficiency, combined
      with recent developments in legislation and engineering, is now allowing X-ray to
      actively compete with gamma irradiation and E-beam as a microbial reduction
      strategy for foods. This review summarizes the historical developments of X-rays
      and discusses the key technological advances over the past two decades that now
      have led to the development of several different X-ray irradiators capable of
      enhancing the safety and shelf life of many heat-sensitive products, including
      lettuce, spinach, tomatoes, and raw almonds, all of which have been linked to
      high profile outbreaks of foodborne illness.

PMID- 22149075
TI  - Cold plasma decontamination of foods.
AB  - Cold plasma is a novel nonthermal food processing technology that uses energetic,
      reactive gases to inactivate contaminating microbes on meats, poultry, fruits,
      and vegetables. This flexible sanitizing method uses electricity and a carrier
      gas, such as air, oxygen, nitrogen, or helium; antimicrobial chemical agents are
      not required. The primary modes of action are due to UV light and reactive
      chemical products of the cold plasma ionization process. A wide array of cold
      plasma systems that operate at atmospheric pressures or in low pressure treatment
      chambers are under development. Reductions of greater than 5 logs can be obtained
      for pathogens such as Salmonella, Escherichia coli O157:H7, Listeria
      monocytogenes, and Staphylococcus aureus. Effective treatment times can range
      from 120 s to as little as 3 s, depending on the food treated and the processing
      conditions. Key limitations for cold plasma are the relatively early state of
      technology development, the variety and complexity of the necessary equipment,
      and the largely unexplored impacts of cold plasma treatment on the sensory and
      nutritional qualities of treated foods. Also, the antimicrobial modes of action
      for various cold plasma systems vary depending on the type of cold plasma
      generated. Optimization and scale up to commercial treatment levels require a
      more complete understanding of these chemical processes. Nevertheless, this area
      of technology shows promise and is the subject of active research to enhance
      efficacy.

PMID- 22149076
TI  - Encapsulation of new active ingredients.
AB  - The organic construct consumed as food comes packaged in units that carry the
      active components and protect the entrapped active materials until delivered to
      targeted human organs. The packaging and delivery role is mimicked in the
      microencapsulation tools used to deliver active ingredients in processed foods.
      Microencapsulation efficiency is balanced against the need to access the
      entrapped nutrients in bioavailable forms. Encapsulated ingredients boosted with
      bioactive nutrients are intended for improved health and well-being and to
      prevent future health problems. Presently, active ingredients are delivered using
      new techniques, such as hydrogels, nanoemulsions, and nanoparticles. In the
      future, nutraceuticals and functional foods may be tailored to individual
      metabolic needs and tied to each person's genetic makeup. Bioactive ingredients
      provide health-enhancing nutrients and are protected through encapsulation
      processes that shield the active ingredients from deleterious environments.

PMID- 22149077
TI  - Positive technology: using interactive technologies to promote positive
      functioning.
AB  - It is generally assumed that technology assists individuals in improving the
      quality of their lives. However, the impact of new technologies and media on well
      being and positive functioning is still somewhat controversial. In this paper, we
      contend that the quality of experience should become the guiding principle in the
      design and development of new technologies, as well as a primary metric for the
      evaluation of their applications. The emerging discipline of Positive Psychology
      provides a useful framework to address this challenge. Positive Psychology is the
      scientific study of optimal human functioning and flourishing. Instead of drawing
      on a "disease model" of human behavior, it focuses on factors that enable
      individuals and communities to thrive and build the best in life. In this paper,
      we propose the "Positive Technology" approach--the scientific and applied
      approach to the use of technology for improving the quality of our personal
      experience through its structuring, augmentation, and/or replacement--as a way of
      framing a suitable object of study in the field of cyberpsychology and human
      computer interaction. Specifically, we suggest that it is possible to use
      technology to influence three specific features of our experience--affective
      quality, engagement/actualization, and connectedness--that serve to promote
      adaptive behaviors and positive functioning. In this framework, positive
      technologies are classified according to their effects on a specific feature of
      personal experience. Moreover, for each level, we have identified critical
      variables that can be manipulated to guide the design and development of positive
      technologies.

PMID- 22149078
TI  - The present and future of positive technologies.
AB  - The goal of this work is to delimit the field of Positive Technology--the
      scientific and applied approach to the use of technology for improving the
      quality of our personal experience. This new field combines the objectives of
      Positive Psychology with enhancements of Information and Communication
      Technologies (ICTs) by focusing on three key variables--emotional quality,
      engagement/actualization, and connectedness--that are able to transform our
      personal experience in a tool for building new and enduring personal resources.
      In fact, Positive Technologies include those designed to manipulate the quality
      of experience through its structuring, augmentation and/or replacement, with the
      goal of increasing wellness, and generating strengths and resilience in
      individuals, organizations, and society. This work describes existing Positive
      Technologies, classified according to their objectives: hedonic (mood-altering
      devices, which use ICTs to induce positive and pleasant experiences); eudaimonic
      (systems designed to support individuals in reaching engaging and self
      actualizing experiences); and social/interpersonal (technologies that seek to
      improve the connectedness between individuals, groups, and organizations).
      Finally, possible directions of future developments are suggested.

PMID- 22149079
TI  - Examining the complexity of human RNA polymerase complexes using HaloTag
      technology coupled to label free quantitative proteomics.
AB  - Efficient determination of protein interactions and cellular localization remains
      a challenge in higher order eukaryotes and creates a need for robust technologies
      for functional proteomics studies. To address this, the HaloTag technology was
      developed for highly efficient and rapid isolation of intracellular complexes and
      correlative in vivo cellular imaging. Here we demonstrate the strength of this
      technology by simultaneous capture of human eukaryotic RNA polymerases (RNAP) I,
      II, and III using a shared subunit, POLR2H, fused to the HaloTag. Affinity
      purifications showed successful isolation, as determined using quantitative
      proteomics, of all RNAP core subunits, even at expression levels near endogenous.
      Transient known RNAP II interacting partners were identified as well as three
      previously uncharacterized interactors. These interactions were validated and
      further functionally characterized using cellular imaging. The multiple
      capabilities of the HaloTag technology demonstrate the ability to efficiently
      isolate highly challenging multiprotein complexes, discover new interactions, and
      characterize cellular localization.

PMID- 22149080
TI  - Ag-SiO2 core-shell nanorod arrays: morphological, optical, SERS, and wetting
      properties.
AB  - Using the hydrolysis of tetraethylorthosilicate, a uniform and conformal layer of
      porous SiO(2) with controlled thickness has been coated onto the oblique angle
      deposited Ag nanorod (AgNR) array to form an aligned AgNR-SiO(2) core-shell array
      nanostructure. The morphology, optical property, SERS response, and surface
      wettability of the AgNRs with different SiO(2) shell thicknesses have been
      obtained by multiple characterization techniques. The morphological
      characterization shows that each AgNR on the array is coated with a uniform and
      porous silica shell independently and the growth of shell thickness follows a
      linear function versus the coating time. Thickening of the shell induces a
      monotonic decrease of the apparent contact angle, red-shift of the transverse
      mode of the localized surface plasmon resonance peak, and makes the SiO(2) shell
      more compact. The SERS response of 4-Mercaptophenol on these substrates exhibits
      an exponential decay behavior with the increasing coating time, which is ascribed
      to the decreasing Ag surface coverage of core-shell nanorods. Under the
      assumption that the Ag surface coverage is proportional to the SERS intensity,
      one can estimate the evolution of SiO(2) coverage on AgNRs. Such coverage
      evolution can be used to qualitatively explain the LSPR wavelength change and
      quantitatively interpret the contact angle change based on a double Cassie's law.

PMID- 22149081
TI  - Harnessing Online Peer Education (HOPE): integrating C-POL and social media to
      train peer leaders in HIV prevention.
AB  - Novel methods, such as Internet-based interventions, are needed to combat the
      spread of HIV. While past initiatives have used the Internet to promote HIV
      prevention, the growing popularity, decreasing digital divide, and multi
      functionality of social networking sites, such as Facebook, make this an ideal
      time to develop innovative ways to use online social networking sites to scale
      HIV prevention interventions among high-risk groups. The UCLA Harnessing Online
      Peer Education study is a longitudinal experimental study to evaluate the
      feasibility, acceptability, and preliminary effectiveness of using social media
      for peer-led HIV prevention, specifically among African American and Latino Men
      who have Sex with Men (MSM). No curriculum currently exists to train peer leaders
      in delivering culturally aware HIV prevention messages using social media.
      Training was created that adapted the Community Popular Opinion Leader (C-POL)
      model, for use on social networking sites. Peer leaders are recruited who
      represent the target population and have experience with both social media and
      community outreach. The curriculum contains the following elements: discussion
      and role playing exercises to integrate basic knowledge of HIV/AIDS, awareness of
      sociocultural HIV/AIDS issues in the age of technology, and communication methods
      for training peer leaders in effective, interactive social media-based HIV
      prevention. Ethical issues related to Facebook and health interventions are
      integrated throughout the sessions. Training outcomes have been developed for
      long-term assessment of retention and efficacy. This is the first C-POL
      curriculum that has been adapted for use on social networking websites. Although
      this curriculum has been used to target African-American and Latino MSM, it has
      been created to allow generalization to other high-risk groups.

PMID- 22149082
TI  - Influence of physical exercise and gender on acetylcholinesterase and
      butyrylcholinesterase activity in human blood samples.
AB  - The determination of cholinesterase activity in plasma and erythrocytes serves as
      a useful and sensitive biomarker of exposure to organophosphorus and carbamate
      pesticides. However, acetylcholinesterase (AChE) and butyrylcholinesterase
      (BuChE) activity may be influenced by factors such as age, gender, drugs, and
      physical exercise. The aim of this study was to evaluate the effects of gender
      and physical exercise on the activity of AChE and BuChE in healthy individuals.
      The values for both enzymes were lower for women. Physical exercise increased the
      levels of BuChE, and had no significant effect on AChE. To our knowledge, this is
      the first clinical study evaluating the influence of physical exercise in levels
      of these enzymes. Considering that cholinesterase activity is a useful parameter
      in assessing the exposure of individuals to pesticides, it is important to
      understand factors that influence the determination of the enzymes in order to
      avoid the erroneous interpretation of results.

PMID- 22149086
TI  - miR23b ameliorates neuropathic pain in spinal cord by silencing NADPH oxidase 4.
AB  - AIMS: Neuropathic pain is a well-known type of chronic pain caused by damage to
      the nervous system. Until recently, researchers have been primarily focused on
      identifying the cellular or chemical sources of neuropathic pain or have
      approached neuropathic pain via the basis of biological study. We investigated
      whether mmu-mir-23b (miR23b) infusion can alleviate pain by compensating for the
      abnormally downregulated miR23b by reducing the expression of its target gene,
      NADPH oxidase 4 (NOX4), a reactive oxygen species (ROS) family member
      overexpressed in neuropathic pain. RESULTS: Ectopic miR23b expression effectively
      downregulated NOX4 and was normalized to GAD65/67 expression. Moreover, the
      animals with neuropathic pain showed significant improvements in the paw
      withdrawal thresholds following miR23b infusion. Normalizing miR23b expression in
      tissue lesions caused by neuropathic pain induction reduced inflammatory mediator
      expression and increased the level of several ROS scavengers. Moreover, GABAergic
      neurons coexpressed suboptimal levels of miR23b and elevated NOX4/ROS after pain
      induction at the cellular level. MiR23b protects GABAergic neurons against
      ROS/p38/JNK-mediated apoptotic death. By evaluating the functional behavior of
      the mice receiving pain/miR23b, normal/anti-miR23b, or anti-miR23b/si-NOX4, the
      positive role of miR23b and the negative role of NOX4 in neuropathic pain were
      confirmed. INNOVATION AND CONCLUSION: Based on this study, we conclude that
      miR23b plays a crucial role in the amelioration of neuropathic pain in the
      injured spinal cord by inactivating its target gene, NOX4, and protecting
      GABAergic neurons from cell death. We finally suggest that miR23b may provide
      attractive diagnostic and therapeutic resources for effective pain modulation in
      neuropathic pain.

PMID- 22149087
TI  - Marker-based classification of young-elderly gait pattern differences via direct
      PCA feature extraction and SVMs.
AB  - The classification of gait patterns has great potential as a diagnostic tool, for
      example, for the diagnosis of injury or to identify at-risk gait in the elderly.
      The purpose of the paper is to present a method for classifying group differences
      in gait pattern by using the complete spatial and temporal information of the
      segment motion quantified by the markers. The classification rates that are
      obtained are compared with previous studies using conventional classification
      features. For our analysis, 37 three-dimensional marker trajectories were
      collected from each of our 24 young and 24 elderly female subjects while they
      were walking on a treadmill. Principal component analysis was carried out on
      these trajectories to retain the spatial and temporal information in the markers.
      Using a Support Vector Machine with a linear kernel, a classification rate of
      95.8% was obtained. This classification approach also allowed visualisation of
      the contribution of individual markers to group differentiation in position and
      time. The approach made no specific assumptions and did not require prior
      knowledge of specific time points in the gait cycle. It is therefore directly
      applicable for group classification tasks in any study involving marker
      measurements.

PMID- 22149088
TI  - One-pot synthesis of core-expanded naphthalene diimides: enabling N-substituent
      modulation for diverse n-type organic materials.
AB  - A mild and versatile one-pot synthesis of core-expanded naphthalene diimides has
      been developed, which undergoes a nucleophilic aromatic substitution reaction and
      then an imidization reaction, allowing an easy and low-cost access to diverse n
      type organic materials. Some newly synthesized compounds by this one-pot
      operation exhibited high electron mobility of up to 0.70 cm(2) V(-1) s(-1) in
      ambient conditions.

PMID- 22149089
TI  - What happens after graduation? Outcomes, employment, and recommendations of
      recent junior/community college graduates with and without disabilities.
AB  - PURPOSE: The objective was to compare employment status of junior/community
      college graduates with and without disabilities. METHODS: We compared post
      graduation outcomes of 182 graduates with and 1304 without disabilities from
      career/technical and pre-university programs from three junior/community
      colleges. Findings for graduates who had registered for disability related
      services from their school and those who had not were examined separately.
      Reported academic obstacles and facilitators were also compared. RESULTS: Few
      employment differences between graduates with and without disabilities were
      found. Two-thirds of career/technical graduates from both groups were employed,
      approximately 30% were studying, and less than 3% were either looking for work or
      "unavailable for work." Over 80% of pre-university graduates in both groups were
      continuing their studies; here, too, numbers of employed graduates (14% with and
      13% without disabilities) were similar and very few in both groups (<2%) were
      either looking for work or "unavailable for work." Full versus part-time
      employment of these two groups was very similar and the same proportion of
      graduates with and without disabilities were working in jobs related to their
      studies. Only in "closely related" work did graduates without disabilities have
      the advantage. CONCLUSIONS: Employment prospects for junior/community college
      graduates with disabilities seem to be quite positive.

PMID- 22149091
TI  - Global histone H3K27 methylation levels are different in localized and metastatic
      prostate cancer.
AB  - Global histone modification patterns have been shown to be a predictive factor of
      recurrence in various cancers. We analyzed global histone-3-lysine-27 (H3K27)
      methylation in prostate cancer (PCA) tissues. H3K27 mono-, di-, and tri
      methylation patterns were different in nonmalignant prostate tissue, localized
      PCA, metastatic PCA, and castration-resistant PCA. H3K27 mono-methylation was
      correlated with pT-stage, capsular penetration, seminal vesicle infiltration, and
      Gleason score in localized PCA and may therefore indicate adverse prognosis.

PMID- 22149090
TI  - Opportunistic intestinal infections and risk of colorectal cancer among people
      with AIDS.
AB  - Because mucosal inflammation contributes to colorectal carcinogenesis, we studied
      the impact of intestinal infections on risk of this malignancy among people with
      AIDS (PWA). Using the population-based HIV/AIDS Cancer Match, which includes
      approximately half of all PWA in the United States, the cancer registries
      ascertained colorectal cancers (ICD-O3 codes C180-C189, C199, C209, and C260).
      During 4-120 months after AIDS onset, risk of cancer occurring after AIDS
      defining intestinal infections (considered as time-dependent exposures) was
      estimated with hazard ratios (HR) and 95% confidence intervals (CI) calculated by
      Cox regression. Analyses included cancers overall and by histology and anatomic
      site. After excluding 118 squamous cell rectal cancers (possible anal cancers),
      we analyzed 320 incident colorectal cancer cases that occurred among 471,909 PWA.
      Colorectal cancer risk was marginally elevated following cryptosporidiosis
      (HR=2.08, 95% CI=0.93-4.70, p=0.08) and mucocutaneous herpes (HR=1.69, 95%
      CI=0.97-2.95, p=0.07) but not with Pneumocystis pneumonia (HR=0.79, 95% CI=0.57
      1.10). Cryptosporidiosis was associated with rare colon squamous cell carcinoma
      [N=8, HR=13, 95% CI=1.5-110] and uncommon histologies [HR=4.4, 95% CI=1.1-18,
      p=0.04], but it was not associated with colorectal adenocarcinoma (N=269, HR=1.3,
      95% CI=0.4-3.9, p=0.70). Mucocutaneous herpes was associated with colon squamous
      cell carcinoma (HR=13, 95% CI=2.4-67, p=0.003) but not with colorectal
      adenocarcinoma (HR=1.3, 95% CI=0.6-2.6, p=0.52) or uncommon histologies (HR=2.5,
      95% CI=0.8-8.2, p=0.13). Colon squamous cell carcinoma risk was significantly
      elevated among PWA who had cryptosporidiosis or mucocutaneous herpes. These
      findings might suggest that HPV or inflammation from other infection may
      contribute to carcinogenesis.

PMID- 22149092
TI  - Targeted therapy for patients with chronic myeloid leukemia: clinical trial
      experience and challenges in inter-trial comparisons.
AB  - The treatment of chronic myeloid leukemia (CML) was revolutionized by the
      introduction of the targeted tyrosine kinase inhibitor (TKI) imatinib mesylate.
      Later, to improve efficacy and tolerability, the more potent TKIs dasatinib and
      nilotinib were evaluated in CML. Clinicians comparing the clinical efficacy of
      TKIs face considerable challenges, including the variable treatment histories of
      patients receiving second-line therapy. The aim of this review is to highlight
      the pitfalls and possible solutions for comparing efficacy across disparate CML
      trials. Comparison of efficacy across trials is aided by careful consideration of
      possible confounding factors, including treatment history, definitions of
      imatinib intolerance or resistance, and BCR-ABL mutational status at baseline.
      However, methods exist to improve the comparability of data from different
      trials, yielding a more clinically and statistically meaningful inter-trial
      comparison.

PMID- 22149094
TI  - A prelearning manipulation falsifies a pure associational deficit account of
      retrieval shift during skill acquisition.
AB  - Older adults adopt memory-based response strategies during consistent practice
      more slowly and less completely than younger adults. In two experiments,
      participants either prelearned all, half, or none of the noun-pair stimuli prior
      to the completion of a standard noun-pair lookup task. Higher proportions of
      prelearning generally led to a faster and more complete strategic shift from
      visual scanning to memory retrieval during the lookup task, and a strong
      prelearning criterion for all items eliminated the age-related slowing of
      retrieval shift. However, the 50% prelearned condition resulted in strategy shift
      that was inconsistent with simple mechanistic associative learning, revealing a
      strategic set that was retrieval-avoidant in older adults.

PMID- 22149095
TI  - Electroformation of peptide self-assembled monolayers on gold.
AB  - The application of a potential to deposit a monolayer of 3-mercaptopropionic acid
      histidinyl-histidinyl-histidinyl-aspartyl-aspartyl (3-MPA-HHHDD-OH) controls the
      density and molecular structure of the peptide monolayer, which results in
      different wettabilities of the surface, surface density, orientation of the
      molecule (extended or bent), and nonspecific adsorption of serum proteins. 3-MPA
      HHHDD-OH must be deposited at 200 mV to maintain an extended configuration, which
      promoted low biofouling properties.

PMID- 22149097
TI  - Cytocompatible encapsulation of individual Chlorella cells within titanium
      dioxide shells by a designed catalytic peptide.
AB  - The individual encapsulation of living cells has a great impact on the areas of
      single cell-based sensors and devices as well as fundamental studies in single
      cell-based biology. In this work, living  Chlorella  cells were encapsulated
      individually with abiological, functionalizable TiO(2), by a designed catalytic
      peptide that was inspired by biosilicification of diatoms in nature. The
      bioinspired cytocompatible reaction conditions allowed the encapsulated 
      Chlorella  cells to maintain their viability and original shapes. After formation
      of the TiO(2) shells, the shells were postfunctionalized by using catechol
      chemistry. Our work suggests a bioinspired approach to the interfacing of
      individual living cells with abiological materials in a controlled manner.

PMID- 22149096
TI  - A single sublingual dose of an adenovirus-based vaccine protects against lethal
      Ebola challenge in mice and guinea pigs.
AB  - Sublingual (SL) delivery, a noninvasive immunization method that bypasses the
      intestinal tract for direct entry into the circulation, was evaluated with an
      adenovirus (Ad5)-based vaccine for Ebola. Mice and guinea pigs were immunized via
      the intramuscular (IM), nasal (IN), oral (PO) and SL routes. SL immunization
      elicited strong transgene expression in and attracted CD11c(+) antigen presenting
      cells to the mucosa. A SL dose of 1 * 108 infectious particles induced Ebola
      Zaire glycoprotein (ZGP)-specific IFN-gamma+ T cells in spleen, bronchoalveolar
      lavage, mesenteric lymph nodes and submandibular lymph nodes (SMLN) of naive mice
      in a manner similar to the same dose given IN. Ex vivo CFSE and in vivo cytotoxic
      T lymphocyte (CTL) assays confirmed that SL immunization elicits a notable
      population of effector memory CD8+ T cells and strong CTL responses in spleen and
      SMLN. SL immunization induced significant ZGP-specific Th1 and Th2 type responses
      unaffected by pre-existing immunity (PEI) that protected mice and guinea pigs
      from lethal challenge. SL delivery protected more mice with PEI to Ad5 than IM
      injection. SL immunization also reduced systemic anti-Ad5 T and B cell responses
      in naive mice and those with PEI, suggesting that secondary immunizations could
      be highly effective for both populations.

PMID- 22149098
TI  - Macrophage migration inhibitory factor isolated from a parasite inhibited Th2
      cytokine production in PBMCs of atopic asthma patients.
AB  - BACKGROUND: In a previous study, we demonstrated that the human macrophage
      migration inhibitory factor (MIF)-like protein (As-MIF) isolated from helminths
      could inhibit allergic airway inflammation via the recruitment of
      CD4(+)CD25(+)Foxp3(+) T cells. OBJECTIVE: To evaluate the clinical importance of
      As-MIF as an antiasthma drug, we evaluated immune responses after recombinant As
      MIF (rAs-MIF) treatment in peripheral blood mononuclear cell (PBMC) cultures.
      METHODS: PBMC was isolated from 10 patients with atopic asthma, 8 patients with
      nonatopic asthma, and 12 nonatopic healthy subjects, and various concentrations
      of rAs-MIF were transferred into the PBMC culture medium. After 3 days, we
      measured the levels of T helper 2 and T helper 1 cytokines via ELISA. RESULTS: In
      atopic asthma, IL-4 and IL-5 production was significantly reduced in the PBMC
      cultures after rAs-MIF treatment. These inhibitory effects were not observed in
      the nonatopic asthma group. By way of contrast, IL-10 production in the PMBC
      cultures was significantly increased after rAs-MIF treatment in all experimental
      groups. CONCLUSION: The results of this study are similar to those previously
      reported in a mouse study, suggesting that As-MIF might be a candidate for the
      specific treatment of asthma.

PMID- 22149093
TI  - Cancer cell signaling pathways targeted by spice-derived nutraceuticals.
AB  - Extensive research within the last half a century has revealed that cancer is
      caused by dysregulation of as many as 500 different gene products. Most natural
      products target multiple gene products and thus are ideally suited for prevention
      and treatment of various chronic diseases, including cancer. Dietary agents such
      as spices have been used extensively in the Eastern world for a variety of
      ailments for millennia, and five centuries ago they took a golden journey to the
      Western world. Various spice-derived nutraceuticals, including 1'-acetoxychavicol
      acetate, anethole, capsaicin, cardamonin, curcumin, dibenzoylmethane, diosgenin,
      eugenol, gambogic acid, gingerol, thymoquinone, ursolic acid, xanthohumol, and
      zerumbone derived from galangal, anise, red chili, black cardamom, turmeric,
      licorice, fenugreek, clove, kokum, ginger, black cumin, rosemary, hop, and
      pinecone ginger, respectively, are the focus of this review. The modulation of
      various transcription factors, growth factors, protein kinases, and inflammatory
      mediators by these spice-derived nutraceuticals are described. The anticancer
      potential through the modulation of various targets is also the subject of this
      review. Although they have always been used to improve taste and color and as a
      preservative, they are now also used for prevention and treatment of a wide
      variety of chronic inflammatory diseases, including cancer.

PMID- 22149099
TI  - Human beta-defensins and psoriasin/S100A7 expression in salivary glands: anti
      oncogenic molecules for potential therapeutic approaches.
AB  - BACKGROUND: Host defence peptides (HDPs), including human beta-defensins (hBDs)
      and psoriasin/S100A7, exert antimicrobial and immunoregulatory functions of the
      innate defense system. In addition to these functions, the search for cancer
      biomarkers has identified HDPs as playing a potential role in both tumor
      suppression and oncogenesis. Although HDPs are highly expressed in salivary
      glands, their role as molecules for potential diagnostic and therapeutic
      approaches has not yet been analyzed. OBJECTIVE: The aim of the present study was
      to investigate whether expression levels of putative pro- or anti-oncogenic hBDs,
      including hBD-1, -2, -3, and psoriasin/S100A7, are altered in salivary gland
      tumor tissue as potential targets for molecular-based therapeutic approaches.
      METHODS: We analyzed the expression levels of hBD-1, -2, -3, and psoriasin/S100A7
      by quantitative real-time polymerase chain reaction (qrt-PCR) and
      immunohistochemistry in a case control study by comparing salivary gland tumor
      samples relative to healthy control specimens from 58 patients. Expression level
      analysis of hBD-1, -2, -3, and psoriasin/S100A7 by qrt-PCR was normalized to the
      endogenous 18S rRNA expression levels. RESULTS: The results demonstrate the
      significant downregulation of hBD-1 (p < 0.001), hBD-2 (p = 0.003), hBD-3 (p =
      0.002), and psoriasin/S100A7 (p = 0.003) mRNA in human salivary gland tumors
      compared with healthy control specimens. Protein expression levels of hBD-1, -2, 
      3, and psoriasin/S100A7 in salivary gland tumor tissue were strongly reduced
      compared with healthy control specimens. CONCLUSION: The data indicates a
      putative role of the innate defense system in salivary gland tumor formation. The
      identification of immunoregulatory molecules as diagnostic biomarkers or
      therapeutic targets could provide new approaches for molecular-based diagnostic
      and therapeutic support to treat salivary gland tumors as well as other
      malignancies. We suggest that HDPs should be taken into consideration for use in
      molecular-based therapeutic approaches.

PMID- 22149100
TI  - Quantitative proteomic analysis of membrane proteins involved in astroglial
      differentiation of neural stem cells by SILAC labeling coupled with LC-MS/MS.
AB  - Membrane proteins play a critical role in the process of neural stem cell self
      renewal and differentiation. Here, we apply the SILAC (stable isotope labeling by
      amino acids in cell culture) approach to quantitatively compare the membrane
      proteome of the self-renewing and the astroglial differentiating cells. High
      resolution analysis on a linear ion trap-Orbitrap instrument (LTQ-Orbitrap) at
      sub-ppm mass accuracy resulted in confident identification and quantitation of
      more than 700 distinct membrane proteins during the astroglial differentiation.
      Of the 735 quantified proteins, seven cell surface proteins display significantly
      higher expression levels in the undifferentiated state membrane compared to
      astroglial differentiating membrane. One cell surface protein transferrin
      receptor protein 1 may serve as a new candidate for NSCs surface markers.
      Functional clustering of differentially expressed proteins by Ingenuity Pathway
      Analysis revealed that most of overexpressed membrane proteins in the astroglial
      differentiation neural stem cells are involved in cellular growth, nervous system
      development, and energy metabolic pathway. Taken together, this study increases
      our understanding of the underlying mechanisms that modulate complex biological
      processes of neural stem cell proliferation and differentiation.

PMID- 22149105
TI  - Secondary branching and nitrogen doping of ZnO nanotetrapods: building a highly
      active network for photoelectrochemical water splitting.
AB  - A photoanode based on ZnO nanotetrapods, which feature good vectorial electron
      transport and network forming ability, has been developed for efficient
      photoelectrochemical water splitting. Two strategies have been validated in
      significantly enhancing light harvesting. The first was demonstrated through a
      newly developed branch-growth method to achieve secondary and even higher
      generation branching of the nanotetrapods. Nitrogen-doping represents the second
      strategy. The pristine ZnO nanotetrapod anode yielded a photocurrent density
      higher than those of the corresponding nanowire devices reported so far. This
      photocurrent density was significantly increased for the new photoanode
      architecture based on the secondary branched ZnO nanotetrapods. After N-doping,
      the photocurrent density enjoyed an even more dramatic enhancement to 0.99
      mA/cm(2) at +0.31 V vs Ag/AgCl. The photocurrent enhancement is attributed to the
      greatly increased roughness factor for boosting light harvesting associated with
      the ZnO nanotetrapod branching, and the increased visible light absorption due to
      the N-doping induced band gap narrowing of ZnO.

PMID- 22149106
TI  - Early maladaptive schema factors, pain intensity, depressiveness and pain
      disability: an analysis of biopsychosocial models of pain.
AB  - PURPOSE: To test different biopsychosocial models of pain within two different
      samples. METHOD: Early maladaptive schemas, pain intensity, depressiveness and
      pain disability were assessed using questionnaire data from 271 first visit pain
      patients and 276 municipal employees as controls. Exploratory factor analysis was
      used as the early maladaptive schema factor extraction method and path analysis
      as the model specification and estimation method. RESULTS: Cross-sectionally,
      early maladaptive schema factors were predictors of depressiveness in both
      groups. The effect size of depressiveness on pain disability was 11 times that of
      the pain intensity in the pain patient group. The situation was opposite in the
      control group, where effect size of pain intensity was 5.6 times that of
      depressiveness. In subgroups of pain duration, the effect size of pain intensity
      on pain disability became insignificant when pain duration was more than 2 years
      in pain patients. CONCLUSIONS: The study supported the importance of early
      emotional adversities in predicting depressiveness especially among pain
      patients. Depressiveness was the main predictor of pain disability in the pain
      patient group and as the pain duration increased, the significance of pain
      intensity on disability vanished. Pain intensity was the main predictor of pain
      disability in the control group.?

PMID- 22149107
TI  - Influence of passive smoking on functional abilities in children.
AB  - Passive smoking has been found to be associated with a large number of disorders
      of passive smokers. It seems that the children are the most susceptible
      population for harmful effects of passive smoke exposure. The aim of this study
      was to evaluate the effect of passive smoking on children's functional abilities.
      The target population was 199 children who were 13-15 years old at the time of
      the study. For the assessment of motor skills 6-min run test was used. Children
      exposed to passive smoking by their mothers had statistically significant lower
      functional abilities (r =-0.7029; 95% CI -0.7707 to -0.6194; p < 0.0001). We also
      found statistically significant difference if the both parents are smokers (r =
      0.3343; 95% CI -0.4595 to -0.1961; p < 0.0001). The results of our study did not
      show statistically significant difference if the children are exposed to
      cigarette smoke by their fathers (r = 0.03139; 95% CI -0.1171 to 0.1785; p =
      0.6792). Public health preventive actions should go toward minimizing the
      exposure of children to passive smoking by counseling the smoking parents that
      quitting smoking provides enormous health benefits not only to them but also to
      their children.

PMID- 22149108
TI  - Protein recognition by a self-assembled deep cavitand monolayer on a gold
      substrate.
AB  - This paper details the first use of a self-folding deep cavitand on a gold
      surface. A sulfide-footed deep, self-folding cavitand has been synthesized, and
      its attachment to a cleaned gold surface studied by electrochemical and SPR
      methods. Complete monolayer formation is possible if the cavitand folding is
      templated by noncovalent binding of choline or by addition of space-filling
      thiols to cover any gaps in the cavitand adsorption layer. The cavitand is
      capable of binding trimethylammonium-tagged guests from an aqueous medium and can
      be deposited in 2 * 2 microarrays on the surface for characterization by SPR
      imaging techniques. When biotin-labeled guests are used, the cavitand:guest
      construct can recognize and immobilize streptavidin proteins from aqueous
      solution, acting as an effective supramolecular biosensor for monitoring protein
      recognition.

PMID- 22149109
TI  - The endoplasmic reticulum as the extracellular space inside the cell: role in
      protein folding and glycosylation.
AB  - SIGNIFICANCE: Proteins destined to secretion and exposure on the cell surface are
      synthesized and processed in the extracellular-like environment of the
      endoplasmic reticulum (ER) of higher eukaryotic cells. Compartmentation plays a
      crucial role in the post-translational modifications, such as oxidative folding
      and N-glycosylation in the ER lumen. Transport of the required intermediates
      across the ER membrane and maintenance of the luminal redox conditions and Ca(2+)
      ion concentration are indispensable for appropriate protein maturation. RECENT
      ADVANCES: Cooperation of enzymes and transporters to maintain a thiol-oxidizing
      milieu in the ER lumen has been recently elucidated. Ca(2+)-dependence of certain
      ER chaperones is a subject of intensive research. CRITICAL ISSUES: Mounting
      evidence supports the existence of a real barrier between the ER lumen and the
      cytosol. The unique set of enzymes, selection of metabolites, and characteristic
      ion and redox milieu of the luminal compartment strongly argue against the
      general permeability of the ER membrane. FUTURE DIRECTIONS: Alterations in the
      luminal environment can trigger the unfolded protein response, a common event in
      a variety of pathological conditions. Therefore, redox and calcium homeostasis
      and protein glycosylation in the ER provide novel drug-targets for medical
      treatment in a wide array of diseases.

PMID- 22149118
TI  - Room-temperature terahertz detectors based on semiconductor nanowire field-effect
      transistors.
AB  - The growth of semiconductor nanowires (NWs) has recently opened new paths to
      silicon integration of device families such as light-emitting diodes, high
      efficiency photovoltaics, or high-responsivity photodetectors. It is also
      offering a wealth of new approaches for the development of a future generation of
      nanoelectronic devices. Here we demonstrate that semiconductor nanowires can also
      be used as building blocks for the realization of high-sensitivity terahertz
      detectors based on a 1D field-effect transistor configuration. In order to take
      advantage of the low effective mass and high mobilities achievable in III-V
      compounds, we have used InAs nanowires, grown by vapor-phase epitaxy, and
      properly doped with selenium to control the charge density and to optimize source
      drain and contact resistance. The detection mechanism exploits the nonlinearity
      of the transfer characteristics: the terahertz radiation field is fed at the gate
      source electrodes with wide band antennas, and the rectified signal is then read
      at the output in the form of a DC drain voltage. Significant responsivity values
      (>1 V/W) at 0.3 THz have been obtained with noise equivalent powers (NEP) < 2 *
      10(-9) W/(Hz)(1/2) at room temperature. The large existing margins for technology
      improvements, the scalability to higher frequencies, and the possibility of
      realizing multipixel arrays, make these devices highly competitive as a future
      solution for terahertz detection.

PMID- 22149119
TI  - Influence of differing material properties in media and adventitia on arterial
      adaptation--application to aneurysm formation and rupture.
AB  - Experimental and computational studies suggest a substantial variation in the
      mechanical responses and collagen fibre orientations of the two structurally
      important layers of the arterial wall. Some observe the adventitia to be an order
      of magnitude stiffer than the media whilst others claim the opposite.
      Furthermore, studies show that molecular metabolisms may differ substantially in
      each layer. Following a literature review that juxtaposes the differing layer
      specific results we create a range of different hypothetical arteries: (1) with
      different elastic responses, (2) different fibre orientations, and (3) different
      metabolic activities during adaptation. We use a finite element model to
      investigate the effects of those on: (1) the stress response in homeostasis; (2)
      the time course of arterial adaptation; and (3) an acute increase in luminal
      pressure due to a stressful event and its influence on the likelihood of aneurysm
      rupture. Interestingly, for all hypothetical cases considered, we observe that
      the adventitia acts to protect the wall against rupture by keeping stresses in
      the media and adventitia below experimentally observed ultimate strength values.
      Significantly, this conclusion holds true in pathological conditions.

PMID- 22149120
TI  - Differential sensitivity to life stress in FMR1 premutation carrier mothers of
      children with fragile X syndrome.
AB  - OBJECTIVE: The premutation of the FMR1 gene (defined as between 55 and 200 CGG
      repeats) is estimated to affect 1 in 149 females and 1 in 643 males, and some
      people who carry the FMR1 premutation display signs of impairment. METHOD: This
      study focuses on 82 premutation carrier mothers (M age = 51.4 years; SD = 7.7) of
      adolescent and adult children with fragile X syndrome (FXS). A Gene * Environment
      interaction approach examined the ways in which the experience of negative life
      events interacts with genetic vulnerability to predict depressive symptoms,
      anxiety, and daily cortisol levels. RESULTS: The associations of life events with
      all 3 dependent measures were associated with CGG repeat length but in a
      curvilinear manner. Mothers with midsize CGG repeats who experienced above
      average numbers of negative life events in the previous year had more depressive
      symptoms and anxiety and had a blunted cortisol awakening response, as compared
      with those with higher or lower repeat lengths. However, mothers with midsize CGG
      repeats who experienced below-average numbers of negative life events in the
      previous year had the lowest levels of depressive symptoms and anxiety, and they
      exhibited the typical cortisol response to awakening, meeting the criteria for
      differential susceptibility. CONCLUSIONS: This research extends our understanding
      of the phenotypic effects of the expansion of the FMR1 gene, and it adds to the
      growing literature on the curvilinear relationship between CGG repeat length and
      mental and physical health.

PMID- 22149121
TI  - The relevance of personality assessment in patients with hyperventilation
      symptoms.
AB  - OBJECTIVE: Relatively few data are available concerning the relations between
      hyperventilation symptoms and general personality traits in clinical populations.
      A clear picture of the personality traits associated with hyperventilation
      symptoms could enhance early detection of those individuals who are at risk for
      developing hyperventilation. The aim of this study was to investigate the role of
      general personality in hyperventilation syndrome. METHOD: Patients (N = 364) with
      symptoms not explained by an organic disease and supposedly caused by
      hyperventilation completed the NEO Five-Factor Inventory, the General Health
      Questionnaire--12, and the Nijmegen Questionnaire. Patients were also subjected
      to a hyperventilation provocation test and transcutaneous carbon dioxide
      (TcPCO(2)) values were registered. RESULTS: The results showed that patients with
      hyperventilation obtained mean Neuroticism scores above the normative mean.
      Moreover, only Neuroticism was positively linked with self-reported
      hyperventilation symptoms, and personality traits were more strongly related to
      self-reported complaints than to objective physical information. Neuroticism
      clearly differentiated between different diagnostic groups on the basis of
      Nijmegen Questionnaire and TcPCO(2) values, and an additional small effect of
      Agreeableness was observed. CONCLUSIONS: The present study contributes to the
      evidence that Neuroticism is strongly associated with self-reported
      hyperventilation symptoms, and provides substantial evidence that Neuroticism is
      a vulnerability factor in the development of hyperventilation. Therefore,
      personality assessment may be helpful in advancing the understanding and the
      early detection of hyperventilation symptoms.

PMID- 22149122
TI  - What do men understand about lifetime risk following genetic testing? The effect
      of context and numeracy.
AB  - OBJECTIVE: Genetic testing for gene mutations associated with specific cancers
      provides an opportunity for early detection, surveillance, and intervention
      (Smith, Cokkinides, & Brawley, 2008). Lifetime risk estimates provided by genetic
      testing refer to the risk of developing a specific disease within one's lifetime,
      and evidence suggests that this is important for the medical choices people make,
      as well as their future family and financial plans. The present studies tested
      whether adult men understand the lifetime risks of prostate cancer informed by
      genetic testing. METHOD: In 2 experiments, adult men were asked to interpret the
      lifetime risk information provided in statements about risks of prostate cancer.
      Statement format was manipulated such that the most appropriate interpretation of
      risk statements referred to an absolute risk of cancer in experiment 1 and a
      relative risk in experiment 2. RESULTS: Experiment 1 revealed that few men
      correctly interpreted the lifetime risks of cancer when these refer to an
      absolute risk of cancer, and numeracy levels positively predicted correct
      responding. The proportion of correct responses was greatly improved in
      experiment 2 when the most appropriate interpretation of risk statements referred
      instead to a relative rather than an absolute risk, and numeracy levels were less
      involved. CONCLUSION: Understanding of lifetime risk information is often poor
      because individuals incorrectly believe that these refer to relative rather than
      absolute risks of cancer.

PMID- 22149123
TI  - Impact of alcohol harm reduction strategies in community sports clubs: pilot
      evaluation of the Good Sports program.
AB  - OBJECTIVE: Approximately 4.5 million Australians are involved in community sports
      clubs. A high level of alcohol consumption tends to be commonplace in this
      setting. The only program of its type in the world, the Good Sports program was
      designed to reduce harmful alcohol consumption in these Australian community
      sports clubs. The program offers a staged accreditation process to encourage the
      implementation of alcohol harm-reduction strategies. METHOD: We conducted a
      postintervention adoption study to evaluate whether community sports club
      accreditation through the Good Sports program was associated with lower rates of
      alcohol consumption. We examined alcohol consumption rates in 113 clubs (N =
      1,968 participants) and compared these to consumption rates in the general
      community. We hypothesized that members of clubs with more advanced
      implementation of the Good Sports accreditation program (Stage Two) would consume
      less alcohol than those with less advanced implementation (Stage One). RESULTS:
      Multilevel modeling (MLM) indicated that on days when teams competed, Stage Two
      club members consumed 19% less alcohol than Stage One club members. MLM also
      indicated that the length of time a club had been in the Good Sports program was
      associated with reduced rates of weekly drinking that exceeded Australian short
      term risky drinking guidelines. However consumption rates for all clubs were
      still higher than the general community. Higher accreditation stage also
      predicted reduced long-term risky drinking by club members. CONCLUSION: Our
      findings suggest that community sports clubs show evidence of higher levels of
      alcohol consumption and higher rates of risky consumption than the general
      community. Implementation of the Good Sports accreditation strategy was
      associated with lower alcohol consumption in these settings.

PMID- 22149124
TI  - Religious coping moderates the relationship between emotional functioning and
      obesity.
AB  - OBJECTIVE: Prospective research indicates that poor emotional functioning
      predicts obesity. The maladaptive coping hypothesis proposes that unhealthy
      eating is used to regulate emotion, leading to obesity. Given research suggesting
      that many utilize religion to cope with distress, we hypothesized that positive
      and negative religious coping would moderate links between emotional functioning
      and obesity. In addition, previous research focused on Christians and the
      relevance of religious coping to the Jewish context, where obesity may be of
      particular concern, was examined. METHOD: 212 Jewish participants completed self
      report health and emotional functioning measures as well as the Jewish Religious
      Coping scale. RESULTS: Moderation analysis indicated that negative coping had no
      effect, while positive coping was a significant moderator. Specifically, poor
      emotional functioning predicted increased obesity among those with low, but not
      high, positive religious coping. This effect remained even after several possible
      confounding factors were controlled for, and the effect was large. CONCLUSIONS:
      These findings further support the maladaptive coping hypothesis, indicating that
      religious coping may provide an alternative strategy to maladaptive eating. They
      also illustrate a possible mechanism by which religiosity correlates with better
      health and support the relevance of religious coping to the Jewish context.

PMID- 22149125
TI  - Looking, feeling, and doing: are there age differences in attention, mood, and
      behavioral responses to skin cancer information?
AB  - OVERVIEW: Previous studies on aging and attention to emotional information found
      that older adults may look away from negative stimuli to regulate their moods.
      However, it is an open question whether older adults' tendency to look less at
      negative material comes at the expense of learning when negative information is
      also health-relevant. This study investigated how age-related changes in
      attention to negative but relevant information about skin cancer risk reduction
      influenced both subsequent health behavior and mood regulation. METHODS: Younger
      (18-25 years of age, n = 78) and older (60-92 years of age, n = 77) adults'
      fixations toward videos containing negatively valenced content and risk-reduction
      information about skin cancer were recorded with eye-tracking. Self-reported mood
      ratings were measured throughout. Behavioral outcome measures (e.g., answering
      knowledge questions about skin cancer, choosing a sunscreen, completing a skin
      self-exam) assessed participants' learning of key health-relevant information,
      their interest in seeking additional information, and their engagement in
      protective behaviors. RESULTS: Older adults generally looked less at the negative
      video content, more rapidly regulated their moods, and learned fewer facts about
      skin cancer; yet, they engaged in a greater number of protective behaviors than
      did younger adults. CONCLUSIONS: Older adults may demonstrate an efficient
      looking strategy that extracts important information without disrupting their
      moods, and they may compensate for less learning by engaging in a greater number
      of protective behaviors. Younger adults may be distracted by disruptions to their
      mood, constraining their engagement in protective behaviors.

PMID- 22149126
TI  - Daytime and nighttime sleep patterns in adolescents with and without chronic
      pain.
AB  - OBJECTIVE: The aims of the current study were to characterize daytime and
      nighttime sleep patterns of adolescents with chronic pain, and to compare their
      sleep patterns to a healthy age- and sex-matched cohort. METHODS: Sixty-one
      adolescents from a pain clinic and 60 age- and sex-matched youth from the
      community (mean age = 15.07; 69% female) participated. Participants underwent 10
      days of actigraphic sleep monitoring to assess total sleep time (minutes of
      estimated sleep at night), wake minutes after initial sleep onset, sleep
      efficiency, and occurrence of sleep during the day. RESULTS: Adolescents with
      chronic pain and healthy youth had similar nighttime sleep patterns (total sleep
      time, wake minutes after initial sleep onset, and sleep efficiency). However,
      adolescents with chronic pain spent more time sleeping during the day than their
      healthy peers. Longer daytime sleep was associated with more activity limitations
      in youth with chronic pain. CONCLUSIONS: Although previous research using self
      report methodology has indicated that adolescents with chronic pain commonly
      endorse poor sleep, findings from the current study suggest that these complaints
      may not be explained by differences in nighttime sleep patterns as measured by
      actigraphy. Use of multidimensional sleep assessment may help to understand the
      potential impact of sleep on chronic pain in adolescents.

PMID- 22149127
TI  - Test of a model of the effects of parental illness on youth and family
      functioning.
AB  - OBJECTIVE: Parental illness (PI) may have adverse impacts on youth and family
      functioning. Research in this area has suffered from the absence of a guiding
      comprehensive framework. This study tested a conceptual model of the effects of
      PI on youth and family functioning derived from the Family Ecology Framework
      (FEF; Pedersen & Revenson, 2005). METHOD: A total of 85 parents with multiple
      sclerosis and 127 youth completed questionnaires at Time 1 and 12 months later at
      Time 2. RESULTS: Structural equation modeling results supported the FEF with
      regards to physical-illness disability. Specifically, the proposed mediators
      (role redistribution, stress, and stigma) were implicated in the processes that
      link parental disability to several domains of youth adjustment. The results
      suggest that the effects of parental depression (PD) are not mediated through
      these processes; rather, PD directly affects family functioning, which in turn
      mediates the effects onto youth adjustment. Family functioning further mediated
      between PD and youth well-being and behavioral-social difficulties. CONCLUSIONS:
      Although results support the effects of parental-illness disability on youth and
      family functioning via the proposed mediational mechanisms, the additive effects
      of PD on youth physical and mental health occur through direct and indirect (via
      family functioning) pathways, respectively.

PMID- 22149128
TI  - The psychological impact of test results following diagnostic coronary CT
      angiography.
AB  - OBJECTIVE: Coronary computed tomography (CT) angiography is an advanced cardiac
      imaging test commonly used for diagnosing early signs of ischemic heart disease.
      Despite its importance in cardiology, little is known about its psychological
      effect on patients. The present study sought to examine these effects in relation
      to illness perceptions, cardiac health behavior intentions, and subsequent health
      behaviors. METHODS: Forty-five nonacute cardiac patients who were referred for
      diagnostic coronary CT angiography completed questionnaires prior to testing and
      following the receipt of test results, at which point illness perceptions and
      intentions to take cardiac medication, as well as diet and exercise intentions
      were measured. Exercise and dietary behaviors were measured at follow-up 6 weeks
      later. Changes on these variables were then compared between patients diagnosed
      with normal arteries and patients diagnosed with diseased arteries. RESULTS:
      Compared to positive-testing patients, patients with normal test results reported
      significant changes toward more positive illness perceptions following testing,
      with improvements in emotional effect of illness, illness concern, consequences,
      and personal control of illness. The illness perception of treatment control was
      seen as more important among positive-testing patients, whereas both groups
      reported increases in illness coherence. Health behavior intentions (cardiac
      medication intentions and exercise intentions) increased for positive-testing
      patients only, as did physical activity at follow-up. CONCLUSIONS: Diagnosis
      dependent psychological effects can be detected following coronary CT
      angiography. These effects have important implications for patient health and
      health care in diagnostic contexts, and the results from this study can be used
      to guide further research in this area.

PMID- 22149129
TI  - Impact of social comparison on cancer survivors' quality of life: an experimental
      field study.
AB  - OBJECTIVE: For cancer survivors, the recovery phase after hospital treatment can
      be bothersome. Social comparison information from fellow cancer survivors can
      improve the quality of life in this situation. METHOD: In a randomized field
      experiment, 139 Dutch cancer survivors (M(age) = 52 years; 70.5% women) were
      assigned to a control condition or 1 of 3 experimental conditions in which they
      listened to an interview with fellow cancer survivors. The interview's content is
      about patients' negative emotions and/or the effective coping strategies patients
      used. A validation study among 101 students showed that the conditions were
      perceived as intended. In the main study, quality of life was assessed after 2
      months (using the LASA, Cantrils' Ladder, and 2 items of the EORTC-C30). RESULTS:
      The effects of the interviews depended on the participants' self-reported health
      status and sensitivity to social comparison information (p < .001). Highly
      sensitive patients with a good health status benefited from the information; in
      those not sensitive, quality of life diminished. In patients with a poor health
      status, the effects were reverse. CONCLUSIONS: This study showed that a brief
      intervention comprised of testimonials of fellow cancer survivors had an impact
      on the quality of life of cancer survivors after 2 months. However, subgroups of
      patients were detected whose quality of life decreased because of the
      intervention. These results stress the need to be careful in providing social
      comparison information and to consider side effects of psychosocial
      interventions.

PMID- 22149130
TI  - Mediators of physical activity behavior change: findings from a 12-month
      randomized controlled trial.
AB  - OBJECTIVE: To examine putative mediators of a 12-month motivationally tailored
      physical activity (PA) promotion intervention. DESIGN: We randomly assigned 239
      healthy, underactive adults (moderate-vigorous physical activity <90 min/week;
      mean age = 47.5 years; 82% women) to receive (a) print-based feedback, (b) phone
      based feedback, or (c) contact control. PRIMARY OUTCOME: PA at baseline, 6, and
      12 months, as measured by the 7-day physical activity recall interview.
      MEDIATORS: Four TransTheoretical Model constructs explicitly targeted by the
      intervention (i.e., self-efficacy, decisional balance, cognitive and behavioral
      processes of change), as well as four additional constructs linked to PA behavior
      change (i.e., social support, outcome expectancy, PA enjoyment, exercise-induced
      feelings). RESULTS: Multivariate mediation analyses were used to analyze
      longitudinal PA outcomes. Changes in behavioral processes and one aspect of
      exercise-induced feelings (revitalization) satisfied both action theory (i.e.,
      treatment effects on mediators) and conceptual theory (i.e., mediator effects on
      PA) tests at 6 and 12 months and emerged as statistically significant mediators
      of treatment effects on PA across delivery channels (ps <.014). Cognitive
      processes, self-efficacy, decisional balance, and social support for PA
      participation satisfied Action Theory tests at both 6 and 12 months, but failed
      conceptual theory tests. Delayed intervention effects were observed on other
      aspects of exercise-induced feelings, PA enjoyment, and outcome expectancies, but
      these variables failed mediation testing at 12 months. CONCLUSION: Findings are
      consistent with previous research illustrating the importance of behavioral
      processes of change, but also indicate that affective response to PA may warrant
      more attention as a potential target of behavior change programs.

PMID- 22149131
TI  - Lipid and other plasma markers are associated with anxiety, depression, and
      fatigue.
AB  - OBJECTIVE: Few peripheral metabolites have been shown to be associated with mood
      in healthy individuals or patients with central nervous system diseases. During
      military basic combat training (BCT), mood state, physical performance and body
      composition substantially improve, providing an opportunity to examine
      relationships between mood and nutritional and hormonal biomarkers. METHOD:
      Thirty-five females enrolled in U.S. Marine BCT, an intense physically and
      mentally challenging 12-week course, were studied. Every 4 weeks, mood was
      assessed with the Profile of Mood States (POMS), as were nutritional, metabolic
      and hormonal plasma markers. RESULTS: Mood and fitness improved over BCT, and
      there were substantial changes in biochemical markers. Multiple regression
      demonstrated that, in combination, cholesterol (HDL, LDL), fructosamine,
      triglycerides, free fatty acids (FFA), dehydroepiandrosterone-sulfate (DHEA-S),
      ACTH, and substance P accounted for 44% of variation in anxiety, 40% confusion,
      37% fatigue, 27% depression and 40% in total mood (p < .0001). Increased HDL,
      FFA, DHEA-S, and substance P were associated with degraded mood (p < .05).
      Increased LDL, triglycerides, fructosamine, and ACTH were associated with
      improved mood (p < .05). Other markers, including glucose, cortisol, and C
      reactive protein were not associated with mood. CONCLUSIONS: Normal human mood
      state was associated with 8 plasma markers. Increased HDL and lower LDL, which
      are associated with improved cardiovascular status, were associated with negative
      affect. Fructosamine and substance P, not previously known to be related to mood,
      were associated with it. We are not aware of any biological parameters that in
      aggregate predict such a substantial proportion of variation in normal mood.

PMID- 22149132
TI  - Chemical and enzymatic synthesis of 2-(2-carbamoylethyl)- and 2-(2
      carboxyethyl)aziridines and their conversion into delta-lactams and gamma
      lactones.
AB  - Treatment of 1-arylmethyl-2-(2-cyanoethyl)aziridines with a nitrile hydratase
      afforded the corresponding 2-(2-carbamoylethyl)aziridines, which underwent
      rearrangement into 5-hydroxypiperidin-2-ones upon heating under microwave
      irradiation. In addition, treatment of 2-(2-cyanoethyl)aziridines with a
      nitrilase selectively afforded 5-hydroxypiperidin-2-ones in good yields. On the
      other hand, chemical hydrolysis of 2-(2-cyanoethyl)aziridines using KOH in
      EtOH/H(2)O furnished the corresponding potassium 3-(aziridin-2-yl)propanoates,
      which, upon acidification with acetic acid, smoothly rearranged into 4
      (aminomethyl)butyrolactones.

PMID- 22149133
TI  - Deciphering the nanometer-scale organization and assembly of Lactobacillus
      rhamnosus GG pili using atomic force microscopy.
AB  - In living cells, sophisticated functional interfaces are generated through the
      self-assembly of bioactive building blocks. Prominent examples of such
      biofunctional surfaces are bacterial nanostructures referred to as pili. Although
      these proteinaceous filaments exhibit remarkable structure and functions, their
      potential to design bioinspired self-assembled systems has been overlooked. Here,
      we used atomic force microscopy (AFM) to explore the supramolecular organization
      and self-assembly of pili from the Gram-positive probiotic bacterium
      Lactobacillus rhamnosus GG (LGG). High-resolution AFM imaging of cell
      preparations adsorbed on mica revealed pili not only all around the cells, but
      also in the form of remarkable star-like structures assembled on the mica
      surface. Next, we showed that two-step centrifugation is a simple procedure to
      separate large amounts of pili, even though through their synthesis they are
      covalently anchored to the cell wall. We also found that the centrifuged pili
      assemble as long bundles. We suggest that these bundles originate from a complex
      interplay of mechanical effects (centrifugal force) and biomolecular interactions
      involving the SpaC cell adhesion pilin subunit (lectin-glycan bonds, hydrophobic
      bonds). Supporting this view, we found that pili isolated from an LGG mutant
      lacking hydrophilic exopolysaccharides show an increased tendency to form tight
      bundles. These experiments demonstrate that AFM is a powerful platform for
      visualizing individual pili on bacterial surfaces and for unravelling their two
      dimensional assembly on solid surfaces. Our data suggest that bacterial pili may
      provide a generic approach in nanobiotechnology for elaborating functional
      supramolecular interfaces assembled from bioactive building blocks.

PMID- 22149134
TI  - Long-term health states relevant to young persons with stroke living in the
      community in southern Stockholm - a study of self-rated disability and predicting
      factors.
AB  - PURPOSE: The purpose was to explore self-rated long-term disability and to
      analyze whether initial stroke-related, personal and environmental factors can
      predict disability in a population-based sample of community-dwelling young (<65
      years) persons suffering a stroke in 2000-2006. METHOD: Data on initial stroke
      related, personal and environmental factors were retrieved from medical records.
      A study-specific posted questionnaire was used. RESULTS: Of the 158 young persons
      with stroke, 78% had suffered a mild stroke. Tiredness was the most commonly
      reported mental impairment (86%) followed by impaired memory (67%). A majority
      reported limitations/restrictions in returning to leisure activities (58%) and
      work (52%). Stroke-related, personal and environmental factors failed to predict
      self-reported mental and physical impairments, but predicted activity
      limitations/participation restrictions with an acceptable power of accuracy (0.70
      0.73) but a low sensitivity (0.28-0.59). CONCLUSIONS: A majority of these young
      persons were diagnosed with a mild stroke but experienced long-term mental
      impairments and activity limitations/participation restrictions that could not be
      predicted by initial stroke-related, personal and environmental factors solely.
      Therefore, regular long-term assessments irrespective of initial stroke severity
      are warranted in order to identify disabilities and improve the state of health
      among young persons with stroke when needed.

PMID- 22149135
TI  - Low cytomegalovirus-specific T-cell counts at reactivation are associated with
      progression to high-level viremia or disease in seropositive recipients of
      hematopoietic cell grafts from seropositive but not seronegative donors.
AB  - BACKGROUND AIMS: Identifying patients who spontaneously resolve cytomegalovirus
      (CMV) reactivation could spare these patients from the toxicity of antiviral
      drugs such as ganciclovir. The role of CMV-specific T cells in clearing CMV
      viremia in patients who do not receive ganciclovir has not been evaluated. We
      assessed this in patients with CMV viremia between 50 and 50 000 genome
      copies/mL, because our threshold for initiating ganciclovir is 50 000 copies/mL.
      METHODS: We enumerated CMV-specific T cells in 39 CMV seropositive hematopoietic
      cell transplantation (HCT) recipients within 4 days of the first positive CMV
      polymerase chain reaction (PCR). CMV-specific T cells were defined as cells that
      upon stimulation with CMV lysate or pp65 overlapping peptides produced interferon
      (IFN)-gamma, tumor necrosis factor (TNF)-alpha or interleukin (IL)-2, alone or in
      combination. RESULTS: Among Donor (D+), Recipient (R+) patients, unifunctional
      CMV-specific CD4 T-cells were higher in patients who spontaneously resolved CMV
      viremia (did not receive ganciclovir) versus those who progressed (received
      ganciclovir) (median 0.20 versus 0.02/MUL lysate-stimulated cells, P < 0.05, and
      0.26 versus 0.05/MUL pp65 peptide-stimulated cells, P<0.05). Among D- R+
      patients, there was no difference between patients with spontaneous resolution or
      progression; all subsets of CMV-specific T cells measured were barely detectable,
      in both patients with spontaneous resolution and those with progression.
      CONCLUSIONS: Among D+ R+ patients (but not D- R+ patients), high CMV-specific CD4
      T-cell counts identify patients who can spontaneously resolve CMV reactivation.
      In D- R+ patients, immune mechanisms other than T cells may control the
      progression from reactivation to high-level viremia/disease.

PMID- 22149136
TI  - Encapsulation of yeast cells in colloidosomes.
AB  - Polymeric colloidosomes encapsulating viable Baker's yeast cells were prepared.
      To make the capsules, an aqueous suspension of 153 nm poly(methyl methacrylate-co
      butyl acrylate) latex particles plus yeast cells is emulsified in a continuous
      phase of sunflower oil. By adding a small amount of ethanol to the oil phase, the
      latex particles at the surface of the emulsion droplets aggregate, forming the
      colloidosome shells. The microcapsules have been examined using optical,
      confocal, and scanning electron microscopies. The viability of the yeast cells
      was tested using fluorescent molecular probes. The encapsulated Baker's yeast
      cells were able to metabolize glucose from solution, although at a slower rate
      compared to nonencapsulated yeast. This demonstrates diffusion limitation through
      the colloidosome shell. The diffusive resistance could be increased by
      manufacturing colloidosomes with a double latex shell.

PMID- 22149137
TI  - The Hsp90 inhibitor SNX-7081 synergizes with and restores sensitivity to
      fludarabine in chronic lymphocytic leukemia cells with lesions in the TP53
      pathway: a potential treatment strategy for fludarabine refractory disease.
AB  - Drug resistance in chronic lymphocytic leukemia (CLL) associated with lesions in
      the ATM/TP53 pathway represents a major challenge in clinical management.
      Evidence suggests that heat shock protein-90 (Hsp90) inhibitors may represent a
      therapeutic option in combination with more conventional therapies. We explored
      the effects of combining the Hsp90 inhibitor, SNX-7081, with fludarabine in vitro
      against CLL cells and hematological cell lines. In seven cell lines and 23
      patient samples synergy between SNX-7081 and fludarabine (2-FaraA) was apparent
      in the three TP53 mutated cell lines and at significantly lower concentrations in
      TP53 or ATM dysfunctional patient cells. In 11/13 2-FaraA-resistant patient
      samples, SNX-7081 reduced the 50% inhibitory concentration to within a clinically
      achievable range. Synergy between SNX-7081 and 2-FaraA was evident in both the
      cell lines and patient samples as a significant decrease in cell viability. Our
      data suggest that combining SNX-7081 and fludarabine may be effective in the
      treatment of fludarabine-refractory CLL.

PMID- 22149138
TI  - Distinguishing non-small cell lung adenocarcinoma patients from squamous cell
      carcinoma patients and control individuals using serum profiling.
AB  - Goals of this study were to analyze the ability of mass spectrometry serum
      profiling to distinguish non-small cell lung adenocarcinoma from squamous cell
      carcinoma patients and healthy controls. Sera were obtained from 19
      adenocarcinoma patients, 24 squamous cell carcinoma patients, and 21 controls.
      Identifications of significant mass-to-charge ratio (m/z) peak differences
      between these groups were performed using t-tests. A "leave one out" cross
      validation procedure yielded discriminatory lung adenocarcinoma versus squamous
      cell carcinoma p and ROC curve values of <.0001 and 0.92, respectively. Test
      sensitivity and specificity were 84% and 79%, respectively. This approach could
      aid in lung cancer diagnosis and sub-typing.

PMID- 22149139
TI  - Enhancement of the targeting capabilities of the Paclitaxel-loaded pluronic
      nanoparticles with a glycol chitosan/heparin composite.
AB  - An enhancement of tumor-targeting capability was demonstrated with paclitaxel
      (PTX)-loaded Pluronic nanoparticles (NPs) with immobilized glycol chitosan and
      heparin. The PTX-loaded Pluronic NPs were prepared as described in our previous
      report by means of a temperature-induced phase transition in a mixture of
      Pluronic F-68 and liquid polyethylene glycol (PEG; molecular weight: 400)
      containing PTX. The liquid PEG is used as the solubilizer of PTX, and Pluronic F
      68 is the polymer that encapsulates the PTX. The glycol chitosan and heparin were
      immobilized on the surface of the Pluronic NPs in an aqueous medium, and a
      powdery form of the glycol chitosan/heparin immobilized Pluronic NPs (composite
      NPs) was obtained by freeze-drying. Field emission scanning electron microscopy
      and a particle size analyzer were used to observe the morphology and size
      distribution of the prepared NPs. To apply the composite NPs as a delivery system
      for the model anticancer drug PTX, the release pattern and pharmacokinetic
      parameters were observed, and the tumor growth was monitored by injecting the
      composite NPs into the tail veins of tumor-bearing mice. An enhancement of tumor
      targeting capability of NPs was verified by using noninvasive live animal imaging
      technology to observe the time-dependent excretion profile, the in vivo
      biodistribution, circulation time, and the tumor-targeting capability of
      composite NPs.

PMID- 22149140
TI  - Developing an ICF core set for post-stroke disability assessment and verification
      in Taiwan: a preliminary study.
AB  - PURPOSE: The purpose of this study was to develop an ICF core set for post-stroke
      disability assessment and verification of bio-psycho-social problems. METHOD:
      Using the Delphi method, a consensus process was conducted. In total, 24
      multidisciplinary experts from different institutions completed the consensus
      process. The questionnaire for the study comprised 144 ICF second-level, stroke
      relevant categories. A 5-point Likert-type scale was used by participants to
      weight the impact of each category on activities of daily life after a stroke.
      Consensus of ratings was assessed with Spearman's rho and semi-interquartile
      range indices. The core set for post-stroke disability assessment and
      verification was developed from those categories with a mean score >=4.0 found in
      the third round of the Delphi exercise. RESULTS: The core set for post-stroke
      disability assessment and verification contained 51 categories. Of these, 18
      categories were from the component body functions, one from body structures, 22
      from activities and participation, and 10 from environmental factors. The mean
      (standard deviation) Spearman's rho was 0.72 (0.14), and Cronbach's alpha was
      0.98. CONCLUSIONS: The preliminary core set for post-stroke disability assessment
      and verification can offer comprehensive information on the performance of daily
      life activities of chronic stroke survivors. Further validation is required.

PMID- 22149141
TI  - Asthma self-management is sub-optimal in urban Hispanic and African
      American/black early adolescents with uncontrolled persistent asthma.
AB  - INTRODUCTION: Youth as young as 11 are given responsibility to manage their
      asthma. Yet, little is known regarding early adolescents' asthma self-management
      behaviors. This study characterizes urban early adolescents' asthma self
      management behaviors and perceived responsibility to manage asthma, exploring
      demographic differences and examining the relationship between asthma
      responsibility and disease management. METHODS: About 317 Hispanic and African
      American/Black early adolescents (mean age = 12.71) with persistent, uncontrolled
      asthma reported prevention and symptom management steps, and responsibility for
      asthma care. We used Poisson, cumulative logistic, logistic, and linear mixed
      effects regression models to assess the relationships among demographic
      predictors, prevention and management behaviors, and responsibility for asthma
      care. RESULTS: Fifty percent took 7-9 prevention steps; few saw physicians when
      asymptomatic or took daily medication. When symptomatic, 92% used medication to
      treat symptoms and 56% sought medical attention. Controlling for asthma
      responsibility, fewer older youth reported observing how they feel when asthma is
      likely to start, observing symptom changes, or asking for help. More boys
      reported taking medication daily or upon trigger exposure. Controlling for age,
      gender, and race/ethnicity, those reporting more asthma responsibility were less
      likely to report taking management steps, seeking preventive care, asking for
      help, or going to a doctor/hospital for their asthma. CONCLUSIONS: Early
      adolescents' asthma self-management is suboptimal. With increasing age, they are
      less observant regarding their asthma and less likely to seek help. Although they
      perceive themselves to have greater responsibility for managing their asthma,
      early adolescents do less to care for their asthma, suggesting they are being
      given responsibility for asthma care prematurely.

PMID- 22149142
TI  - Quantum manipulation via atomic-scale magnetoelectric effects.
AB  - Magnetoelectric effects at the atomic scale are demonstrated to afford unique
      functionality. This is shown explicitly for a quantum corral defined by a wall of
      magnetic atoms on a metal surface where spin-orbit coupling is observable. We
      show these magnetoelectric effects allow one to control the properties of systems
      placed inside the corral as well as their electronic signatures; they provide
      powerful alternative tools for probing electronic properties at the atomic scale.

PMID- 22149146
TI  - Alternative technique for laparoscopic port-site closure.
AB  - Abstract 0-polyglactin suture into the abdomen via a puncture through the rectus
      fascia parallel to the fascia defect under visual guidance. Second, we perform a
      similar puncture with the tonsil forceps on the opposite side of the fascia
      defect under direct vision to grasp the suture. This cost-effective maneuver is
      safe and eliminates the need for ancillary port-site closure devices.

PMID- 22149144
TI  - Effect of fish oil on levels of R- and S-enantiomers of 5-, 12-, and 15
      hydroxyeicosatetraenoic acids in mouse colonic mucosa.
AB  - The balance of putative pro- and antiinflammatory lipoxygenase (LOX)-derived S
      hydroxyeicosatetraenoic acids (S-HETEs) in colon mucosa is a potential target for
      modulating colon cancer risk and progression. The biological effects of S-HETEs
      and R-hydroxyeicosatetraenoic acids (produced by distinct pathways) may differ,
      but levels of these compounds in the colon are unknown. The objective of this
      study was to develop chiral methods to characterize hydroxyeicosatetraenoic
      (HETE) enantiomers in colonic mucosa and evaluate the effects of fish oil on HETE
      formation. C57BL/6 mice (COX-1 null, COX-2 null, wild-type) were fed a diet
      supplemented with either olive oil or menhaden oil for 11 wk, and R-/S-HETEs in
      colonic mucosa were quantified by chiral LC-MS/MS. The R-enantiomer comprised 60
      72% of 5-HETE, 18-58% of 15-HETE, and 1-16% of 12-HETE in colonic mucosa,
      suggesting that non-LOX sources contribute to HETE profiles. Fish oil reduced
      levels of both R- and S-HETEs, and increased the preponderance of the R
      enantiomers (particularly 12- and 15-HETEs). There was apparent shunting of
      arachidonic acid to 12-/15-LOX in the COX-1 null animals. This is the first
      report of the enantiomeric composition of HETEs in the colon in vivo and shows
      large effects of fish oil in the normal colon.

PMID- 22149145
TI  - Integrated proteomic and metabolomic analysis of larval brain associated with
      diapause induction and preparation in the cotton bollworm, Helicoverpa armigera.
AB  - Diapause is a developmental arrest that allows an organism to survive unfavorable
      environmental conditions and is induced by environmental signals at a certain
      sensitive developmental stage. In Helicoverpa armigera, the larval brain receives
      the environmental signals for diapause induction and then regulates diapause
      entry at the pupal stage. Here, combined proteomic and metabolomic differential
      display analysis was performed on the H. armigera larval brain. Using two
      dimensional electrophoresis, it was found that 22 proteins were increased and 27
      proteins were decreased in the diapause-destined larval brain, 37 of which were
      successfully identified by MALDI-TOF/TOF mass spectrometry. RT-PCR and Western
      blot analyses showed that the expression levels of the differentially expressed
      proteins were consistent with the 2-DE results. Furthermore, a total of 49
      metabolites were identified in the larval brain by GC-MS analysis, including 4
      metabolites at high concentrations and 14 metabolites at low concentrations. The
      results gave us a clue to understand the governing molecular events of the
      prediapause phase. Those differences that exist in the induction phase of
      diapause-destined individuals are probably relevant to a special memory mechanism
      for photoperiodic information storage, and those differences that exist in the
      preparation phase are likely to regulate accumulation of specific energy reserves
      in diapause-destined individuals.

PMID- 22149143
TI  - Pilot studies for development of an HIV subtype panel for surveillance of global
      diversity.
AB  - The continued global spread and evolution of HIV diversity pose significant
      challenges to diagnostics and vaccine strategies. NIAID partnered with the FDA,
      WRAIR, academia, and industry to form a Viral Panel Working Group to design and
      prepare a panel of well-characterized current and diverse HIV isolates. Plasma
      samples that had screened positive for HIV infection and had evidence of recently
      acquired infection were donated by blood centers in North and South America,
      Europe, and Africa. A total of 80 plasma samples were tested by quantitative
      nucleic acid tests, p24 antigen, EIA, and Western blot to assign a Fiebig stage
      indicative of approximate time from initial infection. Evaluation of viral load
      using FDA-cleared assays showed excellent concordance when subtype B virus was
      tested, but lower correlations for subtype C. Plasma samples were cocultivated
      with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells
      (PBMCs) from normal donors to generate 30 viral isolates (50-80% success rate for
      samples with viral load >10,000 copies/ml), which were then expanded to 10(7)
      10(9) virus copies per ml. Analysis of env sequences showed that sequences
      derived from cultured PBMCs were not distinguishable from those obtained from the
      original plasma. The pilot collection includes 30 isolates representing subtypes
      B, C, B/F, CRF04_cpx, and CRF02_AG. These studies will serve as a basis for the
      development of a comprehensive panel of highly characterized viral isolates that
      reflects the current dynamic and complex HIV epidemic, and will be made available
      through the External Quality Assurance Program Oversight Laboratory (EQAPOL).

PMID- 22149147
TI  - Systematic evaluation of a novel foot-pump ureteroscopic irrigation system.
AB  - INTRODUCTION: To evaluate forces exerted on a stone with different ureteroscopic
      irrigation systems. METHODS: A 3 mm steel simulated stone was welded to a 3F
      stone basket and inserted into the working channel of a 4.5F Wolf semirigid
      ureteroscope. The basket shaft was attached to a 50 g load cell. The urterescope
      was placed in a ureteral model (14F silicon tubing). Simulated blood (McCormickTM
      Red Dye, 1 dye drop/15 mL H(2)O) was dripped adjacent to the stone at 12
      drops/min. Endoirrigation devices were attached to the ureterscope and irrigation
      was applied at a rate sufficient to maintain visualization of the stone. Force on
      the stone was measured with the following endoirrigation systems: Boston
      ScientificTM Single-Action-Pump System (SAP) hand-pump and NuVista MedicalTM Flo
      Assist((r)) foot-pump. RESULTS: No significant difference (p=0.19) in the number
      of pumps required to maintain a clear endoscopic field was found between the SAP
      (0.20+/-0.075/second) and Flo-Assist device (0.25+/-0.056/second). The pump
      duration of the Flo-Assist was found to be less (1.12+/-0.40 seconds) than the
      SAP (1.35+/-0.31 seconds), but not significantly different (p=0.24). The average
      maximum impulse was significantly lower (p=0.0002) for the SAP (8.34*10(-5) Ns)
      than the Flo-Assist (1.96*10(-3) Ns). Total maximum impulse (2.02*10(-5) Ns) for
      the SAP and total average impulse (5.51*10(-6) Ns) were found to be lower than
      the Flo-Assist device. The Flo-Assist had a total maximum impulse of 4.49*10(-4)
      Ns and total average impulse of 8.85*10(-6) Ns, however, these differences were
      not statistically significant. CONCLUSION: The hand-pump (SAP) and foot-pump (Flo
      Assist) irrigation devices tested require comparable amounts of pumps for similar
      durations of time to maintain endoscopic visualization. Overall, the SAP device
      exerts less average maximum force on the stone than the Flo-Assist device.

PMID- 22149148
TI  - Prevalence of Legionella spp. in water systems of hospitals and hotels in South
      Western Greece.
AB  - The aim of the present study was to determine the prevalence of Legionella spp.
      in water systems of hospitals and hotels located in South Western Greece, to
      study the molecular epidemiology of the isolated strains and their possible
      association with bacterial contamination (total count and Pseudomonas
      aeruginosa), the water pH, and temperature. A prevalence survey for Legionella
      spp. by culturing techniques in water distribution systems of eight hospitals and
      nine hotels occurred in South Western Greece. Water sampling and microbiological
      analysis were carried out following the ISO methods. Legionella pneumophila was
      detected in 33% and 36% of the distribution systems of hospitals and hotels,
      respectively. Our survey results suggest a frequent prevalence of elevated
      concentrations of Legionella spp. in water systems of hospitals and hotels. Our
      investigation has confirmed the need to regularly monitor the microbiological
      condition of water systems in hospitals and hotels.

PMID- 22149149
TI  - The effects of print exposure on sentence processing and memory in older adults:
      Evidence for efficiency and reserve.
AB  - The present study was an examination of how exposure to print affects sentence
      processing and memory in older readers. A sample of older adults (N = 139; Mean
      age = 72) completed a battery of cognitive and linguistic tests and read a series
      of sentences for recall. Word-by-word reading times were recorded and generalized
      linear mixed effects models were used to estimate components representing
      attentional allocation to word-level and textbase-level processes. Older adults
      with higher levels of print exposure showed greater efficiency in word-level
      processing and in the immediate instantiation of new concepts, but allocated more
      time to semantic integration at clause boundaries. While lower levels of working
      memory were associated with smaller wrap-up effects, individuals with higher
      levels of print exposure showed a reduced effect of working memory on sentence
      wrap-up. Importantly, print exposure was not only positively associated with
      sentence memory, but was also found to buffer the effects of working memory on
      sentence recall. These findings suggest that the increased efficiency of
      component reading processes that come with life-long habits of literacy buffer
      the effects of working memory decline on comprehension and contribute to
      maintaining skilled reading among older adults.

PMID- 22149150
TI  - Effect of oseltamivir on bleeding risk associated with warfarin therapy: a
      retrospective review.
AB  - BACKGROUND: Warfarin is a commonly used oral anticoagulant and its interaction
      with other drugs can result in serious thrombotic or bleeding events. Currently,
      there is no definitive evidence on the possibility of an interaction between
      warfarin and oseltamivir. OBJECTIVE: The objective of this study was to
      investigate whether a possible drug interaction between oseltamivir and warfarin
      exists. METHODS: A retrospective review of patients on anticoagulation therapy
      who took oseltamivir from 1 September 2009 to 28 February 2010 at Seoul National
      University Hospital, Seoul, Korea, was carried out. RESULTS: Among 15 patients
      who were tested for prothrombin time/international normalized ratio (PT/INR)
      [hereafter referred to as INR] within 10 days of starting oseltamivir therapy and
      had previously stable INR values, seven patients had an increase in INR levels
      after oseltamivir administration, and the other eight patients maintained stable
      INR levels. The mean +/- SD INR value was 2.08 +/- 0.46 prior to the
      administration of oseltamivir and 5.15 +/- 2.00 after treatment with oseltamivir
      (measured a mean +/- SD 5.7 +/- 2.5 days after the first dose of oseltamivir) in
      the INR-increased group and, respectively, 2.03 +/- 0.40 and 1.97 +/- 0.54
      (measured 6.4 +/- 2.5 days after the first dose of oseltamivir) in the INR
      unaffected group. The dosage and duration of oseltamivir treatment were similar
      whether the INR values increased or not. There were bleeding events such as blood
      tinged sputum and bloody ascites in three patients in the INR-increased group.
      The INR level recovered within 5 days after discontinuation of warfarin in these
      three patients. The positivity rates for influenza A H1N1 were not different
      between the INR-increased group and the INR-unaffected group. CONCLUSION: This
      case series suggests the possibility of a potential interaction between warfarin
      and oseltamivir. Further well designed prospective studies and genetic
      evaluations are needed to determine the exact nature of the interaction between
      warfarin and oseltamivir.

PMID- 22149159
TI  - Development of a tactile stimulator with simultaneous visual and auditory
      stimulation using E-Prime software.
AB  - In this study, a tactile stimulator was developed, which can stimulate visual and
      auditory senses simultaneously by using the E-Prime software. This study tried to
      compensate for systematic stimulation control and other problems that occurred
      with previously developed tactile stimulators. The newly developed system
      consists of three units: a control unit, a drive unit and a vibrator. Since the
      developed system is a small, lightweight, simple structure with low electrical
      consumption, a maximum of 35 stimulation channels and various visual and auditory
      stimulation combinations without delay time, the previous systematic problem is
      corrected in this study. The system was designed to stimulate any part of the
      body including the fingers. Since the developed tactile stimulator used E-Prime
      software, which is widely used in the study of visual and auditory senses, the
      stimulator is expected to be highly practical due to a diverse combination of
      stimuli, such as tactile-visual, tactile-auditory, visual-auditory and tactile
      visual-auditory stimulation.

PMID- 22149151
TI  - Pharmacokinetics of a new once-daily controlled-release formulation of
      aceclofenac in Korean healthy subjects compared with immediate-release
      aceclofenac and the effect of food: a randomized, open-label, three-period,
      crossover, single-centre study.
AB  - BACKGROUND: A new controlled-release formulation of aceclofenac 200 mg (Clanza
      CR(r)) developed by Korea United Pharm., Inc., South Korea, for once-daily (od)
      dosing provides biphasic aceclofenac release consisting of immediate release of
      85 mg followed by sustained release of 115 mg. Food has been known to affect the
      rate and extent of absorption of several drugs, in both immediate-release and
      controlled-release formulations. OBJECTIVE: The aim of this study was to evaluate
      the relative bioavailability of a new controlled-release formulation of
      aceclofenac (200 mg od; Clanza CR(r)) in comparison with immediate-release
      aceclofenac (100 mg twice daily [bid], Airtal(r)) and to assess the effect of
      food on the pharmacokinetics of the new controlled-release aceclofenac
      formulation. METHODS: This study was designed as a randomized, open-label, three
      treatment-period, crossover, single-centre study with a 1-week washout in 41
      healthy adults. The three treatments consisted of immediate-release aceclofenac
      100 mg bid administered under fasting conditions; controlled-release aceclofenac
      200 mg od administered under fasting conditions; and controlled-release
      aceclofenac 200 mg od administered immediately after a standardized high-fat
      breakfast. Plasma concentrations of aceclofenac were determined using a high
      performance liquid chromatography method. RESULTS: In the fasted state, the 90%
      confidence intervals (CIs) of the least squares geometric mean ratios (GMRs) for
      the area under the plasma concentration-time curve from time zero to 24 hours
      (AUC(24)) and the peak plasma concentration (C(max)) of aceclofenac for the
      controlled-release and immediate-release formulations of aceclofenac were all
      within the bioequivalence criteria range of 0.8-1.25. The 90% CIs of the GMRs for
      the AUC(24) and C(max) of aceclofenac for the controlled-release formulation of
      aceclofenac in the fed and fasted states were also within the bioequivalence
      range. Both aceclofenac formulations were well tolerated in all subjects, and no
      serious adverse effects were observed. CONCLUSION: The results demonstrate that
      controlled-release aceclofenac 200 mg is equivalent to immediate-release
      aceclofenac 100 mg when administered at the same total daily dose. Additionally,
      the bioavailability of controlled-release aceclofenac was not affected by high
      fat foods.

PMID- 22149160
TI  - Adoptive transfer of virus-directed T cells: will this fly for flu?

PMID- 22149161
TI  - Associations among self-reported balance problems, post-concussion symptoms and
      performance-based tests: a longitudinal follow-up study.
AB  - PURPOSE: The main objectives of this study were to describe long-term self
      reported balance problems and to explore their associations with post-concussion
      symptoms and performance-based tests. METHOD: Prospective study of patients with
      mild traumatic brain injury (MTBI). Self-reported balance problems and post
      concussion symptoms were measured with the Rivermead Post-concussion Symptoms
      Questionnaire at 1 and 4 years after injury. Performance-based tests were
      performed 4 years after injury and included posturography, the Dynamic Gait Index
      (DGI), walking speed tests, and the six-minute walk test. RESULTS: Self-reported
      balance problems were reported in 31% of patients 4 years after injury and
      correlated significantly with post-concussion symptoms. The correlations with
      performance-based tests varied from rho = 0.18 to rho = 0.70 and were strongest
      for the maximum walking speed test (rho = 0.70) and a dual-task test (rho =
      0.43). The DGI had a considerable ceiling effect. CONCLUSIONS: Balance problems
      were long-term consequences of MTBI in one third of this study sample. Self
      reported balance problems correlated with post-concussion symptoms and some of
      the performance-based tests. Future research needs to develop and evaluate
      appropriate rehabilitation strategies that also address the balance problems.

PMID- 22149162
TI  - Roles of hydrogen sulfide in the pathogenesis of diabetes mellitus and its
      complications.
AB  - SIGNIFICANCE: Diabetes and its complications represent a major socioeconomic
      problem. RECENT ADVANCES: Changes in the balance of hydrogen sulfide (H(2)S) play
      an important role in the pathogenesis of beta-cell dysfunction that occurs in
      response to type 1 and type 2 diabetes. In addition, changes in H(2)S homeostasis
      also play a role in the pathogenesis of endothelial injury, which develop on the
      basis of chronically or intermittently elevated circulating glucose levels in
      diabetes. CRITICAL ISSUES: In the first part of this review, experimental
      evidence is summarized implicating H(2)S overproduction as a causative factor in
      the pathogenesis of beta-cell death in diabetes. In the second part of our
      review, experimental evidence is presented supporting the role of H(2)S
      deficiency (as a result of increased H(2)S consumption by hyperglycemic cells) in
      the pathogenesis of diabetic endothelial dysfunction, diabetic nephropathy, and
      cardiomyopathy. FUTURE DIRECTIONS: In the final section of the review, future
      research directions and potential experimental therapeutic approaches around the
      pharmacological modulation of H(2)S homeostasis in diabetes are discussed.

PMID- 22149166
TI  - Light-driven reversible modulation of doping in graphene.
AB  - We report a route to noncovalently latch dipolar molecules on graphene to create
      stable chromophore/graphene hybrids where molecular transformation can be used as
      an additional handle to reversibly modulate doping while retaining high
      mobilities. A light switchable azobenzene chromophore was tethered to the surface
      of graphene via pi-pi interactions, leading to p-doping of graphene with an hole
      concentration of ~5 * 10(12) cm(-2). As the molecules switch reversibly from
      trans to cis form the dipole moment changes, and hence the extent of doping,
      resulting in the modulation of hole concentration up to ~18% by alternative
      illumination of UV and white light. Light-driven conductance modulation and
      control experiments under vacuum clearly attribute the doping modulation to
      molecular transformations in the organic molecules. With improved sensitivities
      these "light-gated" transistors open up new ways to enable optical interconnects.

PMID- 22149165
TI  - Do changes in lifestyle engagement moderate cognitive decline in normal aging?
      Evidence from the Victoria Longitudinal Study.
AB  - OBJECTIVE: Do lifestyle activities buffer normal aging-related declines in
      cognitive performance? The emerging literature will benefit from theoretically
      broader measurement of both lifestyle activities and cognitive performance, and
      longer-term longitudinal designs complemented with dynamic statistical analyses.
      We examine the temporal ordering of changes in lifestyle activities and changes
      in cognitive neuropsychological performance in older adults. METHOD: We assembled
      data (n = 952) across a 12-year (5-wave) period from the Victoria Longitudinal
      Study. Latent change score models were applied to examine whether (and in which
      temporal order) changes in physical, social, or cognitive lifestyle activities
      were related to changes in three domains of cognitive performance. RESULTS: Two
      main results reflect the dynamic coupling among changes in lifestyle activities
      and cognition. First, reductions in cognitive lifestyle activities were
      associated with subsequent declines in measures of verbal speed, episodic memory,
      and semantic memory. Second, poorer cognitive functioning was related to
      subsequent decrements in lifestyle engagement, especially in social activities.
      CONCLUSIONS: The results support the dual contention that (a) lifestyle
      engagement may buffer some of the cognitive changes observed in late life, and
      (b) persons who are exhibiting poorer cognitive performance may also relinquish
      some lifestyle activities.

PMID- 22149167
TI  - Challenging the current approaches to multiple myeloma- and other cancer-related
      bone diseases: from bisphosphonates to targeted therapy.
AB  - An international myeloma meeting entitled "Challenging the current approaches to
      multiple myeloma- and other cancer-related bone diseases: from bisphosphonates to
      targeted therapy" was held in Freiburg, Germany in July 2011 to discuss novel
      insights into and approaches to myeloma bone disease and other bone-seeking
      tumors. This review briefly summarizes the most prominent data of the meeting and
      current literature on our understanding of bone disease, the role of imaging
      techniques, operative interventions and systemic bone-seeking treatment, all of
      which should further improve our future therapeutic choices.

PMID- 22149168
TI  - Expression levels of phosphatase and tensin homolog deleted on chromosome 10
      (PTEN) and focal adhesion kinase in patients with multiple myeloma and their
      relationship to clinical stage and extramedullary infiltration.
AB  - We explored the expression of phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN) and focal adhesion kinase (FAK) mRNA and protein, and
      analyzed the relationship between expression levels and clinical staging and
      extramedullary infiltration in patients with multiple myeloma (MM). The
      expression levels of mRNA and protein were measured by fluorescence quantitative
      polymerase chain reaction (FQ-PCR) and Western blotting. Expressions of PTEN and
      FAK mRNA were significantly different between patients with MM and controls.
      Spearman bivariate correlation analysis showed that PTEN mRNA was significantly
      negatively correlated with FAK mRNA. PTEN and FAK mRNA expressions were
      significantly different between patients with stage I + II MM and stage III MM.
      No difference was found in PTEN mRNA expression, whereas FAK mRNA expression was
      significantly different between patients with MM with and without extramedullary
      infiltration. PTEN protein was higher and total FAK (T-FAK) protein was
      significantly lower in six controls than in 12 patients with stage III MM.
      Phosphorylated FAK (p-FAK) protein was measured as 0.082 +/- 0.040 in 11 patients
      with MM, but not detected in six controls. No significant difference of PTEN and
      T-FAK protein was found, while p-FAK protein was significantly different between
      patients with MM with and without extramedullary infiltration. These results
      indicate that abnormal expression of PTEN and FAK in patients with MM may be
      associated with disease progression and extramedullary infiltration.

PMID- 22149169
TI  - Acarbose is an effective treatment for severe hypertriglyceridemia secondary to l
      asparaginase and dexamethasone.

PMID- 22149170
TI  - The protein interaction network of extracellular vesicles derived from human
      colorectal cancer cells.
AB  - Various mammalian cells including tumor cells secrete extracellular vesicles
      (EVs), otherwise known as exosomes and microvesicles. EVs are nanosized bilayered
      proteolipids and play multiple roles in intercellular communication. Although
      many vesicular proteins have been identified, their functional interrelationships
      and the mechanisms of EV biogenesis remain unknown. By interrogating proteomic
      data using systems approaches, we have created a protein interaction network of
      human colorectal cancer cell-derived EVs which comprises 1491 interactions
      between 957 vesicular proteins. We discovered that EVs have well-connected
      clusters with several hub proteins similar to other subcellular networks. We also
      experimentally validated that direct protein interactions between cellular
      proteins may be involved in protein sorting during EV formation. Moreover,
      physically and functionally interconnected protein complexes form functional
      modules involved in EV biogenesis and functions. Specifically, we discovered that
      SRC signaling plays a major role in EV biogenesis, and confirmed that inhibition
      of SRC kinase decreased the intracellular biogenesis and cell surface release of
      EVs. Our study provides global insights into the cargo-sorting, biogenesis, and
      pathophysiological roles of these complex extracellular organelles.

PMID- 22149171
TI  - Transcriptional regulation of sdiA by cAMP-receptor protein, LeuO, and
      environmental signals in  Salmonella enterica  serovar Typhimurium.
AB  - The sdiA gene encodes for a LuxR-type transcription factor, which is active when
      bound to N-acyl homoserine lactones (AHLs). Because  Salmonella enterica  serovar
      Typhimurium does not produce AHLs, SdiA senses signals produced by other
      organisms. SdiA is not expressed constitutively, and response is limited to
      conditions in which elevated expression occurs, but little is known about the
      regulation of sdiA expression. Here we map the sdiA promoter and define several
      regulators that directly or indirectly act on the promoter. The major activator
      of sdiA expression is cAMP-receptor protein (CRP), and we define the CRP operator
      in the sdiA promoter using promoter and crp mutants. LeuO activates sdiA
      expression to a lesser extent than does CRP. We demonstrate that LeuO directly
      binds the sdiA promoter and the Rcs phosphorelay represses sdiA expression. In
      this study, NhaR, IlvY, and Fur affected sdiA expression indirectly and weakly.
      Expression in late-stationary phase depended on RpoS. AHL-dependent expression of
      the SdiA-regulated gene rck correlated to the observed sdiA transcriptional
      changes in regulator mutants. The data demonstrate that regulation of sdiA
      involves integration of multiple environmental and metabolic signals.

PMID- 22149173
TI  - Multiphoton reactive surfaces using ruthenium(II) photocleavable cages.
AB  - Photoreactive surfaces derived from a new photocleavable surface modification
      agent and with photosensitivity in the Vis and IR region are described. A
      ruthenium(II) caged aminosilane, [Ru(bpy)(2)(PMe(3))(APTS)](PF(6))(2), was
      synthesized and attached to silica surfaces. Light irradiation removed the cage
      and generated surface patterns with reactive amine groups. The photosensitivity
      of this compound under single (460 nm) and two-photon (900) excitation is
      demonstrated. Functional patterns with site-selective attachment of other
      molecular species are described.

PMID- 22149172
TI  - Impact of delay in asthma diagnosis on chest X-ray and antibiotic utilization by
      clinicians.
AB  - OBJECTIVE: To evaluate the effect of the timeliness of asthma diagnosis on chest
      X-ray (CXR) and antibiotic utilization in children. PATIENTS AND METHODS: This
      was a retrospective cohort study of 276 asthmatic children aged 5-12 years from
      Rochester, Minnesota. From the time when children met our predetermined asthma
      criteria, the frequency of CXR and antibiotic utilizations for respiratory
      illnesses were collected from medical records until age 18 years. Using a Poisson
      regression model, the frequency of CXR and antibiotic utilizations were compared
      in children with timely, delayed, or no clinician diagnosis of asthma. RESULTS:
      Of the 276 asthmatic patients, 97 (35%) had a timely diagnosis, 122 (44%) had a
      delayed diagnosis, while 57 patients (21%) had no clinician diagnosis of asthma.
      There was no significant difference in CXR or antibiotic utilization for
      respiratory illness between these groups. In addition, this was true for the
      comparison between the timely diagnosed group and the delayed diagnosed group
      combining both the group with a delay in asthma diagnosis and the group who never
      had asthma diagnosis. CONCLUSIONS: A delay in the diagnosis of asthma in children
      is common and overall it may not influence antibiotic and CXR utilization for
      respiratory symptoms by clinicians. However, its impact on access to asthma
      related therapies and other healthcare utilizations could be possible and was not
      assessed in this study. Given the limitations of our study, a larger prospective
      study needs to be considered.

PMID- 22149174
TI  - Toward the synthesis of (+)-peloruside A via an intramolecular vinylogous aldol
      reaction.
AB  - The use of the intramolecular vinylogous aldol reaction for the preparation of an
      advanced intermediate for the synthesis of peloruside A is described. The
      reaction was applied to compound 19 and proceeds in high yield and good levels of
      diastereoselectivity. Application of the Achmatowicz reaction to this
      intermediate provided the corresponding pyranone, a late stage intermediate well
      positioned for conversion to the natural product.

PMID- 22149176
TI  - Quinoacridine derivatives with one-dimensional aggregation-induced red emission
      property.
AB  - A new series of acceptor-donor-acceptor (A-D-A) type quinoacridine derivatives (1
      3) with aggregation-induced red emission properties were designed and
      synthesized. In these compounds, the electron-withdrawing 2-(3,5
      bis(trifluoromethyl)phenyl)acetonitrile groups act as electron-accepting units,
      while the alkyl-substituted conjugated core acts as electron-donating units. The
      restriction of intramolecular rotation was responsible for the AIE behavior of
      compounds 1-3. All compounds were employed as building blocks to fabricate one
      dimensional (1-D) organic luminescent nano- or microwires based on
      reprecipitation or slow evaporation approaches. Morphological transition from
      zero-dimensional (0-D) hollow nanospheres to 1-D nanotubes has been observed by
      recording SEM and TEM images of aggregated sates of compound 2 in THF/H(2)O
      mixtures at different aging time. It was demonstrated that the synthesized
      compounds with different lengths of alkyl chains displayed different wire
      formation properties. The single-crystal X-ray analysis of compound 2 provided
      reasonable explanation for the formation of 1-D nano- or microstructures.

PMID- 22149175
TI  - SPANosomes as delivery vehicles for small interfering RNA (siRNA).
AB  - Nonionic surfactant vesicles, or SPANosomes (SPs), comprised of cationic lipid
      and sorbitan monooleate (Span 80) were synthesized and evaluated as small
      interfering RNA (siRNA) vectors. The SPs had a mean diameter of less than 100 nm
      and exhibited excellent colloidal stability. The SP/siRNA complexes possessed a
      slightly positive zeta potential of 12 mV and demonstrated a high siRNA
      incorporation efficiency of greater than 80%. Cryogenic transmission electron
      microscopy (cryo-TEM) imaging of the SP/siRNA indicated a predominantly core
      shell structure. The SP/siRNA complexes were shown to efficiently and
      specifically silence expression of both green fluorescent protein (GFP) (66%
      knockdown) and aromatase (77% knockdown) genes in breast cancer cell lines. In
      addition, the cellular trafficking pathway of the SP/siRNA was investigated by
      confocal microscopy using molecular beacons as probes for cytosolic delivery. The
      results showed efficient endosomal escape and cytosolic delivery of the siRNA
      cargo following internalization of the SP/siRNA complexes. In conclusion, Span 80
      is a potent helper lipid, and the SPs are promising vehicles for siRNA delivery.

PMID- 22149177
TI  - The development of IVF practice in Ireland: a personal view.
AB  - This paper traces the development of in vitro fertilization (IVF) in the Republic
      of Ireland from when the first attempts at using this technique were carried out
      in 1985 up to the present. Clinical changes are chronicled principally using the
      personal work of the author and his colleagues as representative of the day. The
      impact of the Catholic Church and the alterations in Medical Council governance
      guidelines over the years as these reflect societal changes are highlighted. The
      potential role of other regulators including Irish case law and the EU Tissue
      directive are discussed as well as the almost invariable private practice nature
      of the services provided and the various ways in which costs have been
      alleviated.

PMID- 22149178
TI  - Prognostic significance of Dicer cellular levels in soft tissue sarcomas.
AB  - In the present study we assessed the expression and distribution of
      endoribonuclease Dicer in soft tissue tumors and correlated its cellular levels
      with clinicopathological parameters, including clinical outcome. Dicer was
      expressed in the tested cell line as well as in the majority of the sarcomas
      examined. Staining intensity was significantly higher in sarcomas compared with
      benign neoplasms and in high-grade compared with low-grade tumors. Elevated Dicer
      immunoreactivity was strongly associated with poor outcome and Dicer cellular
      levels were an independent negative prognostic factor.

PMID- 22149179
TI  - MS and me: exploring the impact of multiple sclerosis on perceptions of self.
AB  - PURPOSE: The aim of this qualitative study was to explore the impact of multiple
      sclerosis (MS) on perceptions of self as well as the emotional, social and
      practical implications of any self-reported changes. METHOD: Twelve participants
      were interviewed and interpretative phenomenological analysis used to analyse the
      data. Participants were recruited from a MS hospital clinic in the north-west of
      England. RESULTS: Four themes were identified although for reasons of space and
      novelty three were discussed, (i) 'my body didn't belong to me': the changing
      relationship to body, (ii) 'I miss the way I feel about myself': the changing
      relationship to self and (iii) 'let's just try and live with it': incorporating
      yet separating MS from self. CONCLUSIONS: The onset of MS was seen to impact upon
      self yet impact did not necessarily equate with a loss of self but rather a
      changed self. Self-related changes did, however, carry the potential to impact
      negatively upon a person's mood and psychological functioning and consequently,
      clinicians are encouraged to consider issues relating to self as standard.

PMID- 22149180
TI  - Decomposition of warning effects in Parkinson's disease.
AB  - Neutral warning signals speed voluntary reactions by reducing temporal
      uncertainty and by triggering a brief burst of arousal. We attempted to isolate
      the phasic arousal mechanism in people with Parkinson's disease (PD) using a
      clock display to minimize temporal uncertainty. In this condition, the speeding
      of responses in a color-discrimination task by an accessory stimulus was the
      fully equivalent to the effect in age-matched control subjects. This indicates
      preserved phasic arousal in PD. Temporal preparation based on warning cues also
      appeared to be normal. By contrast, in a condition with high temporal
      uncertainty, the accessory stimulus (an air puff to the foot) impaired accuracy
      for the patients but not the neurologically normal subjects. The data are
      consistent with the view that PD disrupts internal but not external control of
      alertness.

PMID- 22149181
TI  - Short communication: Increased expression of secretory leukocyte protease
      inhibitor in oral mucosa of Colombian HIV type 1-exposed seronegative
      individuals.
AB  - The exposure to human immunodeficiency virus type 1 (HIV-1) does not always
      result in infection. Indeed, there are individuals who have been repeatedly
      exposed to HIV-1 but do not exhibit clinical or serological evidence of
      infection; they are known as HIV-exposed seronegative individuals (HESN). To
      determine if secretory leukocyte protease inhibitor (SLPI), a soluble factor
      secreted by epithelial cells lining mucosal surfaces that showed anti-HIV
      activity in vitro, was associated with natural resistance to HIV infection, we
      measured by real time RT-PCR the expression of SLPI in oral mucosa of a cohort of
      Colombian HESN, in chronically HIV-1-infected individuals and in healthy
      controls. The HESN expressed significantly higher levels of SLPI mRNA than
      healthy controls (p=0.033) and chronically infected subjects (p=0.011). These
      findings suggest an association between SLPI expression and the natural
      resistance to HIV-1 infection exhibited by our HESN cohort.

PMID- 22149182
TI  - A zeptoliter volume meter for analysis of single protein molecules.
AB  - A central goal in bioanalytics is to determine the concentration of and
      interactions between biomolecules. Nanotechnology allows performing such analyses
      in a highly parallel, low-cost, and miniaturized fashion. Here we report on label
      free volume, concentration, and mobility analysis of single protein molecules and
      nanoparticles during their diffusion through a subattoliter detection volume,
      confined by a 100 nm aperture in a thin gold film. A high concentration of small
      fluorescent molecules renders the aqueous solution in the aperture brightly
      fluorescent. Nonfluorescent analytes diffusing into the aperture displace the
      fluorescent molecules in the solution, leading to a decrease of the detected
      fluorescence signal, while analytes diffusing out of the aperture return the
      fluorescence level. The resulting fluorescence fluctuations provide direct
      information on the volume, concentration, and mobility of the nonfluorescent
      analytes through fluctuation analysis in both time and amplitude.

PMID- 22149183
TI  - Haemodynamic impact of stent-vessel (mal)apposition following carotid artery
      stenting: mind the gaps!
AB  - Carotid artery stenting (CAS) has emerged as a minimally invasive alternative to
      endarterectomy but its use in clinical treatment is limited due to the post
      stenting complications. Haemodynamic actors, related to blood flow in the stented
      vessel, have been suggested to play a role in the endothelium response to
      stenting, including adverse reactions such as in-stent restenosis and late
      thrombosis. Accessing the flow-related shear forces acting on the endothelium in
      vivo requires space and time resolutions which are currently not achievable with
      non-invasive clinical imaging techniques but can be obtained from image-based
      computational analysis. In this study, we present a framework for accurate
      determination of the wall shear stress (WSS) in a mildly stenosed carotid artery
      after the implantation of a stent, resembling the commercially available Acculink
      (Abbott Laboratories, Abbott Park, Illinois, USA). Starting from angiographic CT
      images of the vessel lumen and a micro-CT scan of the stent, a finite element
      analysis is carried out in order to deploy the stent in the vessel, reproducing
      CAS in silico. Then, based on the post-stenting anatomy, the vessel is perfused
      using a set of boundary conditions: total pressure is applied at the inlet, and
      impedances that are assumed to be insensitive to the presence of the stent are
      imposed at the outlets. Evaluation of the CAS outcome from a geometrical and
      haemodynamic perspective shows the presence of atheroprone regions (low time
      average WSS, high relative residence time) colocalised with stent malapposition
      and stent strut interconnections. Stent struts remain unapposed in the ostium of
      the external carotid artery disturbing the flow and generating abnormal shear
      forces, which could trigger thromboembolic events.

PMID- 22149184
TI  - Population dynamics of mesenchymal stromal cells during culture expansion.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) are heterogeneous and only a
      subset possesses multipotent differentiation potential. It has been proven that
      long-term culture has functional implications for MSC. However, little is known
      how the composition of subpopulation changes during culture expansion. METHODS:
      We addressed the heterogeneity of MSC using limiting-dilution assays at
      subsequent passages. In addition, we used a cellular automaton model to simulate
      population dynamics under the assumption of mixed numbers of remaining cell
      divisions until replicative senescence. The composition of cells with adipogenic
      or osteogenic differentiation potential during expansion was also determined at
      subsequent passages. RESULTS: Not every cell was capable of colony formation upon
      passaging. Notably, the number of fibroblastoid colony-forming units (CFU-f)
      decreased continuously, with a rapid decay within early passages. Therefore the
      CFU-f frequency might be used as an indicator of the population doublings
      remaining before entering the senescent state. Predictions of the cellular
      automaton model suited the experimental data best if most cells were already
      close to their replicative limit by the time of culture initiation. Analysis of
      differentiated clones revealed that subsets with very high levels of adipogenic
      or osteogenic differentiation capacity were only observed at early passages.
      CONCLUSIONS: These data support the notion of heterogeneity in MSC, and also with
      regard to replicative senescence. The composition of subpopulations changes
      during culture expansion and clonogenic subsets, especially those with the
      highest differentiation capacity, decrease already at early passages.

PMID- 22149185
TI  - Reduction of galectin-3 expression and liver fibrosis after cell therapy in a
      mouse model of cirrhosis.
AB  - BACKGROUND AIMS: Cirrhosis, end-stage liver disease, is caused by different
      mechanisms of injury, associated with persistent inflammation. Galectin-3 is an
      important regulator of fibrosis that links chronic inflammation to fibrogenesis.
      We investigated the role of bone marrow cell (BMC) transplantation in chronic
      inflammation and hepatic fibrosis. METHODS: Liver cirrhosis was induced by
      administration of carbon tetrachloride and ethanol to wild-type C57BL/6 or bone
      marrow chimeric mice. Bone marrow chimeras were generated by lethal irradiation
      and transplantation with BMC obtained from green fluorescent protein (GFP(+)
      )donors. Wild-type cirrhotic mice were transplanted with BMC without irradiation.
      Livers from chimeras and cirrhotic transplanted mice were obtained for evaluation
      of inflammation, fibrosis and regulatory factors [galectin-3, matrix
      metallopeptidase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 and
      transforming growth factor (TGF)-beta]. RESULTS: The development of cirrhosis was
      associated with increased expression of galectin-3 by F4/80(+) cells and intense
      migration of BMC to the liver. Furthermore, when transplanted after the
      establishment of cirrhosis, BMC also migrated to the liver and localized within
      the fibrous septa. Two months after BMC therapy, cirrhotic mice had a significant
      reduction in liver fibrosis and expression of type I collagen. We did not find
      any difference in levels of TGF-beta, TIMP-1 and MMP-9 between saline and BMC
      groups. However, the numbers of inflammatory cells, phagocytes and galectin-3(+)
      cells were markedly lower in the livers of cirrhotic mice treated with BMC.
      CONCLUSIONS: Our results demonstrate an important role for BMC in the regulation
      of liver fibrosis and that transplantation of BMC can accelerate fibrosis
      regression through modulatory mechanisms.

PMID- 22149187
TI  - Surgical complications after robot-assisted laparoscopic radical prostatectomy:
      the initial 1000 cases stratified by the clavien classification system.
AB  - BACKGROUND AND PURPOSE: Complications after robot-assisted prostatectomy are
      widely reported and varied. Our goal was to determine the incidence of surgical
      complications resulting from robot-assisted laparoscopic radical prostatectomy
      (RALP) during the initial phase of a new robotics program that was developed by
      two surgeons without laparoscopic or robotic fellowship training. A secondary
      goal was to see if experience changed the incidence of complications with this
      technology. PATIENTS AND METHODS: A prospectively maintained database was used to
      evaluate the first 1000 consecutive patients who were treated with RALP from
      January 2004 to June 2009. The database was reviewed for evidence of
      complications in the perioperative period. All patients underwent robot-assisted
      laparoscopic radical prostatectomy by two surgeons. Complications were confirmed
      and supplemented by retrospectively reviewing the departmental morbidity and
      mortality reports, as well as the hospital records. The Clavien classification
      system, a standardized and validated scale for complication reporting, was
      applied to all events. The complication rate was determined per 100 patients
      treated and tested with logistic regression for a relationship with surgeon
      experience. RESULTS: Ninety-seven (9.7%) patients experienced a total of 116
      complications; 81 patients experienced a single complication and 16 patients
      experienced >=2 complications. The majority of complications (71%) were either
      grade I or II. The complication rate decreased with experience when the first 500
      cases were compared with the latter 500 cases (P=0.007). All the data were
      reviewed retrospectively. Involvement of residents/fellows increased as primary
      surgeon experience improved. CONCLUSIONS: Complications after RALP are most
      commonly minor, requiring expectant or medical management only, even during the
      initiation of a RALP program. The complication rate improved significantly during
      the study period.

PMID- 22149186
TI  - Redox sensing: novel avenues and paradigms.
AB  - The response to changes in the redox state of the cell environment is closely
      coupled with the ability of living organisms to sense changing conditions.
      Protein-based redox sensors utilize cofactors, that is, iron-sulfur clusters,
      flavins, or hemes, for environmental sensing. Under oxidizing conditions a
      cofactor-mediated post-translational modification (i.e., thiol-oxidation,
      carbonylation, or dityrosine formation) accompanied by a structural change in the
      protein occurs that results in an appropriate reaction, mostly in terms of
      expression of genes involved in antioxidative stress responses. In addition to
      these well-studied cofactors, researchers have recently discovered and described
      redox-active metabolites that play a role in redox sensing. Furthermore, not only
      proteins but also nucleic acids are able to sense redox-stressing events and to
      elucidate the corresponding response. With these all sensors, organisms are well
      equipped to sense redox-stress signals generated extracellularly as well as
      cytoplasmatically. To analyze the molecular mechanisms of all these redox sensors
      as well as to describe the paradigms involved, a number of sophisticated tools
      have been applied. These include development of novel protein fluorescence
      resonance energy transfer probes to microscopically analyze redox signaling in
      cells or the application of X-ray crystallography combined with spectroscopic
      studies to monitor dynamics of conformational changes within redox sensors. In
      this Forum, novel redox-sensing systems, novel avenues, and recent technical
      advances in the emerging field of redox sensing are presented.

PMID- 22149196
TI  - Meta-analyses and conflict of interest.

PMID- 22149197
TI  - Producing boundary-breaking texts on disability issues: the personal politics of
      collaboration.
AB  - PURPOSE: This article explores the reflection on a process of inter-collaborative
      team work to produce a photographic book on caregivers' experiences of parenting
      their disabled children. The team of authors consisted of members with diverse
      backgrounds, including media studies, social science and photography. The purpose
      of this article was to explore and gain a deeper understanding of the process of
      boundary breaking, one which is important if we are to develop new knowledges and
      new ways of thinking about disability. METHOD: In-depth interviews were conducted
      with all contributors to the book. RESULTS: Themes emerging from the interviews
      include the existence of different worlds, crossing boundaries, questions about
      expertise, conflicting hopes and expectations, and the ethics of anonymity.
      CONCLUSION: An account of the anxieties, the frustrations and rewarding aspects
      of the collaboration is provided. We conclude that "us" and "them" categorization
      permeates our thinking. It characterizes some of the most simplistic thinking in
      the world of disability--able-bodied vs. disabled. In reality, there are no such
      categories, we all reside along a highly differentiated continuum of changing
      states of impairment and health. If we open ourselves up to this reality, we can
      meet one another and draw on one another's knowledge and experience.

PMID- 22149202
TI  - Family-supportive organization perceptions: validation of an abbreviated measure
      and theory extension.
AB  - Although the concept of family-supportive organization perceptions has been well
      received in the literature, the actual construct has been relatively
      understudied. In the present study, we accomplish two goals. First using
      confirmatory factor analysis, we report on the validation of an abbreviated six
      item measure of family-supportive organization perceptions that demonstrates
      limited measurement error. Second, we link role theory, social support resource
      theory, and the direct effects model of social support, to suggest that the way
      in which family-supportive organization perceptions affect work-family conflict
      is via experiences of domain overload. Contrary to the direct effects model of
      social support, family-supportive organization perceptions do not differentially
      impact work and family overload. Consistent with social support resource theory
      though, the effects of family-supportive organization perceptions on work-to
      family and family to-work conflict are fully mediated via work and family
      overload (respectively). Avenues for future research incorporating family
      supportive organization perceptions are also considered.

PMID- 22149203
TI  - Age, cumulative (dis)advantage, and subjective well-being in employed and
      unemployed Germans: a moderated mediation model.
AB  - The negative impact of unemployment on subjective well-being (SWB) is well known,
      but the role of age in this relationship remains unclear. We suggest that
      cumulative advantage (or disadvantage) associated with the duration of current
      employment status may produce an age-related divergence in SWB between employed
      and unemployed individuals. We used cross-sectional data on employed (n = 1382)
      and unemployed (n = 254) Germans (age 18-42) surveyed in 2005. We found that,
      among currently employed individuals, relatively older age predicted longer
      employment duration (tenure), which was related to higher SWB via higher income
      and higher perceived occupational security. Among currently unemployed
      individuals, age predicted longer unemployment duration, which was associated
      with lower SWB via lower perceived social support. Thus, age was indirectly
      related to higher SWB in employed individuals and to lower SWB in unemployed
      individuals. In this way, cumulative advantage of long-term employment and
      cumulative disadvantage of long-term unemployment contributed to the age-related
      divergence in SWB between employed and unemployed Germans already in the first
      half of working life.

PMID- 22149204
TI  - Organizational work-family resources as predictors of job performance and
      attitudes: the process of work-family conflict and enrichment.
AB  - The goal of the current study was to test a model where organizational resources
      (aimed at managing work and family responsibilities) predict job attitudes and
      supervisor ratings of performance through the mechanisms of work-family conflict
      and work-family enrichment. Employees (n = 174) at a large metropolitan hospital
      were surveyed at two time periods regarding perceptions of family supportive
      supervisor behaviors (FSSB), family supportive organizational perceptions (FSOP),
      bidirectional work-family conflict, bidirectional work-family enrichment, and job
      attitudes. Supervisors were also asked to provide performance ratings at Time 2.
      Results revealed FSSB at Time 1 predicted job satisfaction, organizational
      commitment and intention to leave, as well as supervisor ratings of performance,
      at Time 2. In addition, both work-family enrichment and family-work enrichment
      were found to mediate relationships between FSSB and various organizational
      outcomes, while work-family conflict was not a significant mediator. Results
      support further testing of supervisor behaviors specific to family support, as
      well models that include bidirectional work-family enrichment as the mechanism by
      which work-family resources predict employee and organizational outcomes.

PMID- 22149205
TI  - Omalizumab reduces corticosteroid use in patients with severe allergic asthma:
      real-life experience in Israel.
AB  - OBJECTIVE: Approved by the FDA in 2003, omalizumab is the first recombinant
      humanized monoclonal anti-immunoglobulin E antibody developed for the treatment
      of allergic asthma. Due to the heterogeneity of asthma symptoms, investigation of
      the efficacy of omalizumab in patients outside controlled trials is particularly
      important. The purpose of the current study was to evaluate the efficacy of
      omalizumab as an add-on treatment for allergic asthma in a real-life setting in
      Israel. METHODS: This was a retrospective study based on patient records and
      computerized database for drug dispensing, emergency room visits, and hospital
      admissions. RESULTS: The sample comprised 33 individuals (18 men, 15 women; mean
      age 50.0 +/- 12.2, range 25-79) who were treated with omalizumab for severe
      allergic asthma for a duration of at least 16 weeks. After the initiation of
      omalizumab therapy, the number of patients who used oral or injected
      corticosteroids decreased (p < .003, .03, respectively), as did the median dosage
      of oral corticosteroids (p < .02). Visits to the emergency room decreased from an
      incidence of 0.526 visits per person-year to an incidence of 0.246 per person
      year (p < .05). No adverse reactions to omalizumab were observed. CONCLUSION:
      Omalizumab as an add-on therapy reduced the use of corticosteroids and improved
      the control of asthma, as evidenced by reduced asthma-related emergency room
      visits. This study supports both controlled and uncontrolled studies that have
      demonstrated the efficacy and safety of omalizumab, and particularly those that
      demonstrated effectiveness among severe asthma patients. "Real-life" studies are
      important to identify patients who will most benefit from omalizumab therapy.

PMID- 22149206
TI  - A phase I dose-escalation study of clofarabine in combination with fractionated
      gemtuzumab ozogamicin in patients with refractory or relapsed acute myeloid
      leukemia.
AB  - Clofarabine and gemtuzumab ozogamicin (GO) are active agents against acute
      myeloid leukemia (AML), but have not previously been tested in combination. We
      conducted a phase I study to determine the maximum tolerated dose (MTD) and dose
      limiting toxicities (DLTs) of clofarabine when combined with GO in adult patients
      with relapsed or refractory AML. Twenty patients received clofarabine (10, 20 or
      30 mg/m(2)) on days 1-5, with GO 3 mg/m(2)/day on days 1, 4 and 7. Common dose
      limiting toxicities were prolonged myelosuppression and hepatotoxicity.
      Clofarabine 20 mg/m(2) was the MTD, but with a DLT rate of 0.38 (5/13) - a rate
      that is prohibitively high to recommend for phase II study. The overall response
      rate (complete response [CR] + complete response with incomplete hematologic
      recovery [CRi]) was 42% among all patients. Thus, this combination demonstrated
      activity in relapsed and refractory patients, but further testing of the
      combination using lower doses of GO may identify more favorable rates of toxicity
      while maintaining efficacy.

PMID- 22149207
TI  - MLL-ELL fusion gene in two infants with acute monoblastic leukemia and myeloid
      sarcoma.

PMID- 22149208
TI  - Everything has its place or so we thought: natural killer/T cell lymphoma, nasal
      type in the testes.

PMID- 22149209
TI  - Internally self-assembled submicrometer emulsions stabilized with a charged
      polymer or with silica particles.
AB  - Internally self-assembled submicrometer emulsions were stabilized by F127, by the
      charged diblock copolymer K151, by L300 particles, and by sodium dodecyl sulfate
      (SDS). The stabilization of all investigated internal phases and the impact of
      the stabilizer on them are discussed. The use of charged stabilizers results in a
      highly negative zeta potential of the emulsion droplets, which can be exploited
      as a means to control their adsorption onto charged surfaces. Small-angle X-ray
      scattering and dynamic light scattering were used to determine the internal
      structure and size of the emulsion droplets, respectively.

PMID- 22149210
TI  - Synthesis of highly functionalized chiral 3,3'-disubstituted oxindoles via an
      organocatalytic enantioselective Michael addition of nitroalkanes to
      indolylidenecyanoacetates.
AB  - An efficient bifunctional cinchona alkaloid derived thiourea-promoted
      enantioselective conjugate addition of nitroalkanes to indolylidenecyanoacetates
      has been developed under neat conditions. The process leads to synthetically
      interesting densely functionalized 3,3'-disubstituted oxindoles with creation of
      up to three stereogenic centers.

PMID- 22149211
TI  - Solution-processed LiF for work function tuning in electrode bilayers.
AB  - Although ambient processing is the key to low-cost organic solar cell production,
      high-vacuum thermal evaporation of LiF is often a limiting step, motivating the
      exploration of solution processing of LiF as an alternative electrode interlayer.
      Submonolayer films are realized with the assistance of polymeric micelle reactors
      that enable LiF particle deposition with controlled nanoscale surface coverage.
      Scanning Kelvin probe reveals a work function tunable with nanoparticle coverage
      with higher values than that of bare indium tin oxide (ITO).

PMID- 22149212
TI  - Pt@Pd(x)Cu(y)/C core-shell electrocatalysts for oxygen reduction reaction in fuel
      cells.
AB  - A series of carbon-supported core-shell nanoparticles with Pd(x)Cu(y)-rich cores
      and Pt-rich shells (Pt@Pd(x)Cu(y)/C) has been synthesized by a polyol reduction
      of the precursors followed by heat treatment to obtain the Pd(x)Cu(y)/C (1 <= x
      <= 3 and 0 <= y <= 5) cores and the galvanic displacement of Pd(x)Cu(y) with
      [PtCl(4)](2-) to form the Pt shell. The nanoparticles have also been investigated
      with respect to the oxygen reduction reaction (ORR) in proton-exchange-membrane
      fuel cells (PEMFCs). X-ray diffraction (XRD) analysis suggests that the cores are
      highly alloyed and that the galvanic displacement results in a certain amount of
      alloying between Pt and the underlying Pd(x)Cu(y) alloy core. Transmission
      electron microscopy (TEM) images show that the Pt@Pd(x)Cu(y)/C catalysts (where y
      > 0) have mean particle sizes of <8 nm. Compositional analysis by energy
      dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS)
      clearly shows Pt enrichment in the near-surface region of the nanoparticles.
      Cyclic voltammograms show a positive shift of as much as 40 mV for the onset of
      Pt-OH formation in the Pt@Pd(x)Cu(y)/C electrocatalysts compared to that in Pt/C.
      Rotating disk electrode (RDE) measurements of Pt@PdCu(5)/C show an increase in
      the Pt mass activity by 3.5-fold and noble metal activity by 2.5-fold compared to
      that of Pt/C. The activity enhancements in RDE and PEMFC measurements are
      believed to be a result of the delay in the onset of Pt-OH formation.

PMID- 22149213
TI  - Is incidentally detected pulmonary embolism in cancer patients less severe? A
      case-control study.
AB  - Incidental pulmonary embolism (PE) in cancer patients is usually thought to be of
      mild degree. We investigated the severity of PE and evaluated the potential of
      raising the suspicion of PE in such patients. The computed tomography (CT) extent
      of PE was evaluated in 19 consecutive unsuspected and 19 randomly selected
      symptomatic patients. A clinical pattern useful for suspecting PE was also
      searched. On CT, number of embolized vessels, location of emboli, and simple
      instrumental findings were not different in the two groups. PE is not less severe
      in unsuspected cancer patients; moreover, PE may be clinically suspected in such
      patients.

PMID- 22149214
TI  - Clinical progress in gene therapy: sustained partial correction of the bleeding
      disorder in patients suffering from severe hemophilia B.

PMID- 22149215
TI  - Removal of hexavalent chromium in tannery wastewater by  Bacillus cereus.
AB  - Bacillus cereus  was used to remove chromium (Cr(VI)) from medium containing
      tannery wastewater under different conditions. The maximum rate of Cr(VI) removal
      was attained at a temperature of 37  degrees C, pH of 7.0-9.0, and biomass of 20
      g/L when the initial Cr(VI) concentration was less than 50 mg/L. Under the
      optimum conditions, the Cr(VI) in tannery wastewater was treated with each
      cellular component of B. cereus to detect its ability to reduce Cr(VI). The
      results showed that the removal rate of Cr(VI) for the cell-free extracts could
      reach 92.70%, which was close to that of the whole cells (96.85%), indicating
      that the Cr(VI) reductase generated by B. cereus is primarily intracellular.
      Additionally, during continuous culture of the B. cereus, the strain showed good
      consecutive growth and removal ability. After treatment of 20 mg/L Cr(VI) for 48
      h, the B. cereus was observed by SEM and TEM-EDX. SEM images showed that the B.
      cereus used to treat Cr(VI) grew well and had a uniform cellular size. TEM-EDX
      analysis revealed large quantities of chromium in the B. cereus cells used to
      treat Cr(VI). Overall, the results presented herein demonstrate that B. cereus
      can be used as a new biomaterial to remove Cr(VI) from tannery wastewater.

PMID- 22149216
TI  - Chlorotoxin-modified stealth liposomes encapsulating levodopa for the targeting
      delivery against Parkinson's disease in the MPTP-induced mice model.
AB  - Chlorotoxin (ClTx), originally isolated from scorpion venom of Leiurus
      quinquestriatus, is a 36-amino acid peptide and specifically binds to the brain
      gliomas and proliferating vascular endothelial cells. In this paper, it was first
      used to establish the ClTx-modified stealth liposomes (ClTx-LS) encapsulating
      levodopa (LD) for the targeting drug delivery against the Parkinson's disease
      (PD). After the DSPE-PEG-ClTx was synthesized and identified, the ClTx-LS system
      was prepared and characterized. Its targeting capability was studied in vitro and
      in vivo, and finally its anti-PD activity was evaluated, with non-modified
      liposomes (LS) as control. It was demonstrated through flow cytometry and
      confocal microscopy that ClTx modification highly facilitated the uptake of LS by
      brain microvascular endothelial cells in vitro. After intraperitoneal injection
      to mice, the active targeting system loaded with LD significantly increased the
      distribution of dopamine and dihydroxyphenyl acetic acid, the metabolites of LD,
      in the substantia nigra and striata. In the methyl-phenyl-tetrahydropyridine
      (MPTP)-induced PD mice model, LD-loaded ClTx-LS significantly attenuated the
      serious behavioral disorders and diminished the MPTP-induced loss of tyrosine
      hydroxylase-positive dopaminergic neurons. In conclusion, ClTx-modified LS might
      serve as a targeting delivery system to transport more drugs into the brain for a
      better PD therapy.

PMID- 22149217
TI  - Synthesis, optimization, and characterization of camptothecin-loaded acetalated
      dextran porous microparticles for pulmonary delivery.
AB  - We propose the use of a new biopolymer, acetalated dextran (Ac-DEX), to
      synthesize porous microparticles for pulmonary drug delivery. Ac-DEX is derived
      from the polysaccharide dextran and, unlike polyesters, has tunable degradation
      from days to months and pH neutral degradation products. Ac-DEX microparticles
      fabricated through emulsion techniques were optimized using a variety of
      postprocessing techniques to enhance the respirable fraction for pulmonary
      delivery. Tangential flow filtration resulted in a maximum 37% respirable
      fraction for Ac-DEX porous microparticles, compared to a 10% respirable fraction
      for poly(lactic-co-glycolic acid) (PLGA) porous microparticles. Ac-DEX
      microparticles were of an optimum diameter to minimize macrophage clearance but
      had a low enough theoretical density for deep lung penetration. Transepithelial
      electrical resistance (TEER) measurements showed that the particles did not
      impinge on a monolayer of lung epithelial cells in either air or liquid
      conditions. Also, the release of the chemotherapeutic camptothecin was shown to
      be tunable depending on Ac-DEX degradation time and molecular weight, and drug
      release was shown to be bioactive over a range of concentrations. Our results
      indicate that both release kinetics and fraction of burst release of drug from Ac
      DEX porous microparticles can be tuned by simply changing the Ac-DEX polymer
      properties, affording a large range of formulation options for drug delivery to
      the pulmonary cavity. Overall, Ac-DEX porous microparticles show promise as an
      emerging carrier for pulmonary delivery of drugs to the alveolar region of the
      lung, particularly for the treatment of lung diseases.

PMID- 22149218
TI  - Selective control of gliding microtubule populations.
AB  - First lab-on-chip devices based on active transport by biomolecular motors have
      been demonstrated for basic detection and sorting applications. However, to fully
      employ the advantages of such hybrid nanotechnology, versatile spatial and
      temporal control mechanisms are required. Using a thermo-responsive polymer, we
      demonstrate the selective starting and stopping of modified microtubules gliding
      on a kinesin-1-coated surface. This approach allows the self-organized separation
      of multiple microtubule populations and their respective cargoes.

PMID- 22149219
TI  - Mutagenic and antimutagenic assessment of methanol leaf extract of Myristica
      fragrans (Houtt.) using in vitro and in vivo genetic assays.
AB  - The role of diets in causing cancers necessitates the ongoing search for natural
      antimutagens of promising anticancer therapeutics. This study determined the
      potential anticancer efficacy of the leaf extract of Myristica fragrans (Houtt.).
      Methanol leaf extract of M. fragrans (Houtt.) alone was screened for mutagenicity
      in the bacterial reverse mutation (Ames) test, using the Salmonella typhimurium
      TA100 strain, the Allium cepa, and the mouse in vivo bone marrow micronucleus
      tests. The antimutagenicity of this extract against benzo[a]pyrene- and
      cyclophosphamide-induced mutations was evaluated. An antioxidant test on the
      extract was performed with 2,2-diphenyl-1-picrylhydrazyl, using butylated
      hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as the standards, whereas
      its phytochemicals were elucidated by following the gas chromatography/mass
      spectrometry protocol. In S. typhimurium (TA100), the mutagenicity ratio at
      200,500 and 1,000 ug/well was >2. Cell division in the A. cepa root tips and
      mouse bone marrow was significantly (P <= 0.05) inhibited at 2,000 and 4,000
      mg/kg, whereas the observed chromosomal aberrations and micronucleated
      polychromatic erythrocytes were non-dose-related and were insignificantly (P >=
      0.05) different from the negative control. Inhibition of benzo[a]pyrene- and
      cyclophosphamide-induced mutagenicity by this extract was above 40%. Half-maximal
      inhibitory concentration of the extract in the antioxidant test was lower than
      that of BHA and BHT. Phytochemical compounds, possessing antioxidant activity,
      may be responsible for the observed effects, suggesting a strong antimutagenic
      activity of the MeOH leaf extract of M. fragrans, a necessary characteristic of a
      promising anticancer agent.

PMID- 22149220
TI  - Simulation of the behaviour of the L1 vertebra for different material properties
      and loading conditions.
AB  - Three-dimensional finite element models of the thoracolumbar junction (T12-L2)
      and isolated L1 vertebra were developed to investigate the role of material
      properties and loading conditions on vertebral stresses and strains to predict
      fracture risk. The geometry of the vertebrae was obtained from computed
      tomography images. The isolated vertebra model included an L1 vertebra loaded
      through polymethylmethacrylate plates located at the top and bottom of the
      vertebra, and the segment model included T12 to L2 vertebrae and seven ligaments,
      fibrous intervertebral discs and facet joints. Each model was examined with both
      homogeneous and spatially varying bone tissue properties. Stresses and strains
      were compared for uniform compression and flexion. Including material
      heterogeneity remarkably reduced the stiffness of the isolated L1 vertebra and
      increased the magnitudes of the minimum principal strains and stresses in the mid
      transverse section. The stress and strain distributions further changed when
      physiological loading was applied to the L1 vertebra. In the segment models,
      including heterogeneous material properties increased the magnitude of the
      minimum principal strain by 158% in the centre of the mid-transverse section.
      Overall, the inclusion of heterogeneity and physiological loading increased the
      magnitude of the strains up to 346% in flexion and 273% in compression. 

PMID- 22149221
TI  - A novel self-expanding interwoven nitinol stent for complex femoropopliteal
      lesions: 24-month results of the SUPERA SFA registry.
AB  - PURPOSE: To examine the efficacy and integrity of a novel interwoven self
      expanding nitinol stent system for the treatment of complex femoropopliteal
      lesions in a "real world" medical practice. METHODS: This retrospective analysis
      included 107 consecutive patients (77 men; mean age 68.9 years) with
      atherosclerotic femoropopliteal lesions (occlusions in 31%) who underwent
      implantation of 137 SUPERA stents. The patients were followed for up to 24 months
      by Doppler ultrasound examinations, radiography of the stent, and assessments of
      Rutherford-Becker class and ankle-brachial index (ABI). RESULTS: The mean
      implanted stent length was 111+/-50 mm (range 40-270). Procedure success
      (residual stenosis <30%) was achieved in 99% of procedures. The 6-, 12-, and 24
      month cumulative primary patency rates (+/- standard error) were 93.1%+/-2.5%,
      84.7%+/-3.6%, and 76.1%+/-4.5%, respectively, and the secondary patency rates
      were 99.0%+/-0.1%, 94.8%+/-0.2% and 91.9%+/-0.3%, respectively. Between baseline
      and 24 months, mean ABI increased from 0.68+/-0.14 to 0.87+/-0.10 and the mean
      Rutherford-Becker class decreased from 3.3+/-0.7 to 2.0+/-1.0 (p<0.0001 for
      both). Radiographs performed in 91 patients at a mean of 16.8+/-7.0 months found
      no stent fractures. CONCLUSION: Over a 2-year surveillance period, excellent
      durability without stent fractures was documented after implantation of the
      SUPERA stent in complex femoropopliteal lesions. In addition, significant
      improvements were observed in symptom classification and hemodynamics.

PMID- 22149222
TI  - Long-term outcomes and risk stratification of patency following nitinol stenting
      in the femoropopliteal segment: retrospective multicenter analysis.
AB  - PURPOSE: To investigate the long-term outcomes of nitinol stenting in
      femoropopliteal lesions and to determine the factors associated with restenosis.
      METHODS: Between December 2003 and December 2009, 861 patients (603 men; mean age
      72 years) underwent nitinol stenting of the femoropopliteal segment in 1017
      limbs. A quarter (26%) of the patients had critical limb ischemia. Mean lesion
      length was 152+/-93 mm. Stent patency was assessed by either duplex ultrasound or
      angiography and analyzed by Kaplan-Meier estimation. The determinants of
      restenosis were explored with Cox proportional hazard regression analyses; the
      results are presented as the hazard ratio (HR) and 95% confidence interval (CI).
      Risk stratification of primary patency was subsequently analyzed using a score
      based on the significant prognostic factors identified in the multivariate model.
      RESULTS: Stent fracture occurred in 10% (104 limbs) of the lesions. At 1, 3, and
      6 years, the primary patency rates were 77%, 67%, and 63%; secondary patency
      rates were 91%, 87%, and 87%; freedom from femoropopliteal bypass grafting was
      99%, 97%, and 96%, respectively. Multivariate Cox regression analysis identified
      female gender (HR 1.899; 95% CI 1.318 to 2.737, p<0.001), ankle-brachial index
      <0.6 (HR 1.921; 95% CI 1.348 to 2.736, p<0.001), TASC II C/D lesion (HR 2.068;
      95% CI 1.346 to 3.177, p = 0.0009), stent fracture (HR 1.937; 95% CI 1.203 to
      3.118, p = 0.006), and the absence of cilostazol administration (HR 2.102; 95% CI
      1.394 to 3.172, p<0.001) as strong independent factors associated with
      restenosis. After assigning a risk score based on the outcomes of the
      multivariate regression analysis (1 each for female gender, ABI <0.6, TASC II
      C/D, stent fracture, and absence of cilostazol therapy), primary patency was
      found to be lower in limb groups with a higher cumulative score (12-month primary
      patency: score 0: 93%, score 1: 80%, score 2: 73%, score 3; 47%, score 4: 0%,
      respectively; p<0.001). CONCLUSION: Endovascular therapy using nitinol stents for
      FP lesions yielded acceptable outcomes up to 6 years. Risk stratification for
      patency can play an important role in estimating future occurrence of restenosis
      after nitinol stent implantation in FP lesions.

PMID- 22149223
TI  - Use of the reversed Zenith iliac limb extension in the treatment of iliac artery
      aneurysms and various aortoiliac pathologies: outcome in midterm follow-up.
AB  - PURPOSE: To report the midterm follow-up after treatment of various aortoiliac
      pathologies in an acute setting using reversed Zenith iliac limb extensions when
      appropriately sized stent-grafts were not available. METHODS: From 2005 to 2007,
      12 patients (10 men; mean age 71.5 +/- 7.3 years) were treated with reversed
      Zenith iliac limb extensions for solitary iliac artery aneurysms (n = 8), an
      abdominal aortic aneurysm (AAA) in a small caliber aorta (n = 1), an anastomotic
      pseudoaneurysm in an aortobi-iliac graft (n = 1), a hypogastric artery aneurysm
      (n = 1), and a ruptured AAA secondary to a late type Ib endoleak after Talent
      stent-graft implantation (n = 1). The Zenith iliac limb extensions were deployed
      on the back table and reloaded in a reversed manner to treat aneurysms and other
      lesions with a broad range of different diameter necks and landing zones.
      RESULTS: The technical success rate was 100%, and no endoleaks were present at
      the end of the procedures. The endoleak patient with the ruptured AAA died owing
      to respiratory insufficiency. The other 11 patients have a mean follow-up of 29+/
      9 months. In this period, 2 patients received a femorofemoral crossover bypass
      because of an occluded iliac limb extension. One patient had a type II endoleak
      without growth of the iliac aneurysm. Two patients died of a ruptured 4.4-cm AAA
      at 16 months and of respiratory insufficiency due to metastases at 47 months,
      respectively. CONCLUSION: When necessary, it is feasible to use a revered Zenith
      limb extension to treat solitary iliac aneurysms and other aortoiliac
      pathologies, achieving satisfactory midterm outcomes.

PMID- 22149224
TI  - Commentary: off-label use of reversed Zenith limb extension stent-grafts to treat
      different types of aortoiliac aneurysmal disease.

PMID- 22149225
TI  - Endoleak after endovascular aneurysm repair: evaluation of a single-acquisition
      CTA protocol using a prebolus.
AB  - PURPOSE: To investigate a single-acquisition computed tomographic angiography
      (CTA) protocol using a prebolus injection technique to visualize the stent-graft
      lumen and endoleak after endovascular aneurysm repair (EVAR). METHODS: Of 162
      EVAR patients referred for CTA over a 2-year period, 18 (15 men; mean age 66.4
      years) with an endoleak met the study inclusion criteria, which included constant
      endoleak size and scans using 3 different CT protocols at least once during
      follow-up: monophasic CTA (C1), biphasic CTA (C2.1 and C2.2), and single
      acquisition CTA using a prebolus (PB). All CTA examinations were performed with
      the same overall volume of contrast medium (120 mL) and were started manually
      using a bolus-tracking technique. Attenuation was measured within the aortic
      lumen proximal to the stent prosthesis (Ao) and within the endoleak itself (EL).
      RESULTS: Mean attenuation ranged between 200 (C2.2) and 313 HU (C2.1) within Ao
      and between 172 (C2.2) and 235 HU (C2.1) within the endoleak. The attenuation
      differences between Ao (C1) and Ao (PB), as well as between Ao (C2.1) and Ao
      (PB), were not statistically significant, while the attenuations of Ao (C2.2) and
      Ao (PB) differed significantly (p<0.001), with higher attenuation in PB. Compared
      to EL (PB), none of the mean EL attenuation values (C1, C2.1, and C2.2) differed
      significantly. CONCLUSION: This prebolus CTA protocol combines late-phase
      attenuation of a biphasic image acquisition protocol for endoleak visualization
      with high opacification of the stent lumen without exposing the patient to
      radiation twice.

PMID- 22149226
TI  - Interdisciplinary and translational innovation: the endurant stent graft...from
      bedside to benchtop and back to bedside.

PMID- 22149227
TI  - Commentary: endurant stent graft: a new-generation device for a new generation of
      vascular specialist.

PMID- 22149228
TI  - Short- and midterm results of the fascia suture technique for closure of femoral
      artery access sites after endovascular aneurysm repair.
AB  - PURPOSE: To evaluate the midterm outcomes and potential risk factors associated
      with the fascia suture technique (FST) for closure of femoral artery access sites
      after percutaneous endovascular aneurysm repair (EVAR). METHODS: Between April
      2007 and April 2008, 100 consecutive EVAR cases were evaluated retrospectively. A
      third of the procedures were emergent (16 ruptured aneurysms). Of the 187 femoral
      access sites, 160 (85.5%) were closed by the FST as a first choice. Pre- and
      postoperative chart and imaging data were collected from computerized medical
      records for analysis of demographics and the rate of complications (bleeding,
      infection, thrombosis, pseudoaneurysms, and stenosis). Preoperative risk factors
      for FST failure were analyzed with regard to obesity (based on the subcutaneous
      fat layer), plaque at the femoral access site, and stenosis based on the pre- and
      1-year postoperative computed tomography scans. RESULTS: Of the 160 FST closures,
      146 (91.3%) were technically successful. The 14 (8.8%) technical failures were
      converted to open cutdown intraoperatively because of bleeding (11, 6.8%),
      inadequate limb perfusion (2, 1.2%), and a broken guidewire (1, 0.6%). Two (1.2%)
      pseudoaneurysms required surgical repair after 2 weeks. Data from the 1-year
      follow-up showed no signs of increased stenosis, thrombosis, or formation of
      plaque. Nine small (<1 cm(3)) pseudoaneurysms were detected and managed
      conservatively. No preoperative risk factors were associated with FST failure.
      CONCLUSION: The fascia suture technique seems to be safe, effective, and simple
      to use for closing percutaneous access sites after EVAR. Complications are rare,
      and the outcome is not affected by obesity, femoral calcification, or femoral
      artery stenosis.

PMID- 22149229
TI  - Guidewire stiffness: what's in a name?
AB  - PURPOSE: To measure the stiffness of commonly used "stiff" guidewires in terms of
      their flexural modulus, an engineering parameter related to bending stiffness.
      METHODS: Eleven different intact stiff guidewires were selected to undergo a 3
      point bending test performed using a tensile testing machine. Testing was
      performed on 3 new and intact specimens of each guidewire at 10 locations along
      the wire's length, excluding the floppy tip. The flexural modulus (in
      gigapascals, GPa) was calculated from the results of the bending test. RESULTS:
      The flexural modulus of the plain Amplatz wire was 9.5 GPa compared to 11.4 to
      14.5 GPa for the "heavy duty" wires. Within the Amplatz family of guidewires, the
      flexural modulus was 17 GPa for the "stiff," 29.2 GPa for the "extra stiff," 60.3
      GPa for the "super stiff," and 65.4 GPa for the "ultra stiff." The Backup Meier
      measured 139.6 GPa and the Lunderquist Extra Stiff 158.4 GPa. CONCLUSION: The
      Instructions for Use of some endovascular devices specify a wire type selected
      from a range of undefined "stiffness" descriptors. These descriptors have little
      correlation with the measured flexural modulus. Two guidewires with the
      description "extra stiff" can have a 5-fold difference in flexural modulus. We
      recommend that guidewire catalogues and packaging include the flexural modulus
      and that device manufacturers amend their Instructions for Use accordingly.

PMID- 22149230
TI  - Use of covered stents in the central vein: a feasibility study in a canine model.
AB  - PURPOSE: To evaluate the feasibility of using covered stents vs. bare stents in a
      model of central vein stenosis with an arteriovenous graft created to mimic the
      conditions in hemodialysis patients. METHODS: In 7 mongrel dogs, an expanded
      polytetrafluoroethylene-covered nitinol stent was placed in one common iliac vein
      and a bare stent was placed in the contralateral vein. Arteriovenous grafts were
      created bilaterally between the common femoral artery and vein to induce
      endothelial damage. Neointima formation in the covered stents was compared to the
      bare stents at 12 weeks using microscopy and histochemical staining. RESULTS: Two
      dogs were excluded due to thrombosis and infection of the arteriovenous grafts,
      but all stents in the remaining 5 dogs were patent. Smooth, complete neointimal
      coverage was observed on the inner surface of all the covered stents without
      intraluminal thrombus. In contrast, incomplete neointimal coverage was seen in
      all bare stents, with small focal thrombi adhering to the neointima on 3 bare
      stents. Focal nodular neointimal hyperplasia with denudation of the endothelium
      was observed in only 2 bare stents. Mean neointimal thickening was significantly
      greater in the covered stents. Eccentric neointimal thickening was observed at
      the inflow and outflow segments of both types of stents. CONCLUSION: Covered
      stents are technically feasible for the treatment of central vein stenosis, and
      they demonstrate complete, smooth neointimal coverage in normal central veins,
      but they also display greater neointimal thickening than bare stents.

PMID- 22149231
TI  - Contemporary management of giant renal and visceral arteriovenous fistulae.
AB  - PURPOSE: To evaluate our experience with treatment of giant arteriovenous
      fistulae (AVFs) involving the renal and visceral vasculature and assess outcomes.
      METHODS: Clinical data from 12 consecutive patients (10 women; median age 58
      years, range 37-79) undergoing intervention for 14 giant renal/visceral AVFs over
      a 15-year period (1994-2008) were retrospectively reviewed. Only patients with
      extra-parenchymal, wide arteriovenous communications were included. Thirteen were
      located in the renal artery and one in the splenic artery. The etiology was most
      likely post-traumatic/iatrogenic in 6 patients, idiopathic in 4 (1 bilateral),
      congenital in 1 (bilateral), and one was associated with fibromuscular dysplasia.
      In 4 cases, the lesion was asymptomatic. RESULTS: Two large renal AVFs were
      treated with open surgery: one elective AV fistula repair early in our experience
      and the other an emergent nephrectomy for rupture. Twelve AV fistulae were closed
      successfully using endovascular techniques performed solely through the feeding
      vessel without cannulating the draining vein. All symptomatic patients, except
      one with continued dyspnea from cardiac causes, had complete symptomatic relief.
      There was no mortality. Morbidity included 2 access site hematomas that were
      managed conservatively. Loss of renal parenchyma ranged from 5% to 30%, but
      median serum creatinine levels remained stable. CONCLUSION: Endovascular
      treatment of giant renal/visceral AVFs is challenging but feasible and safe, with
      good organ preservation. Endovascular techniques have replaced open surgical
      repair as a first-line treatment for these challenging lesions.

PMID- 22149232
TI  - Re: "pragmatic minimum reporting standards for endovascular abdominal aortic
      aneurysm repair".

PMID- 22149233
TI  - Re: "branched grafts for thoracoabdominal aneurysms: off-label use of FDA
      approved devices" by Dr. Karthik Kasirajan.

PMID- 22149235
TI  - Is novel signal transducer sulfur oxide involved in the redox cycle of persulfide
      at the catalytic site cysteine in a stable reaction intermediate of
      mercaptopyruvate sulfurtransferase?
AB  - Abstract In transsulfuration reaction catalyzed by rat mercaptopyruvate
      sulfurtransferase (MST), a stable persulfide is formed at the catalytic site
      cysteine Cys(247) as a reaction intermediate. The outer sulfur atom is donated by
      the substrate, thiosulfate, or by mercaptopyruvate. MST serves as a thioredoxin
      dependent antioxidant possessing self-regulated enzymatic activity. After
      oxidation of persulfurated MST by treatment with hydrogen peroxide, mass
      spectrometric analysis showed that the outer sulfur atom of the persulfide is
      oxidized to form Cys-thiosulfenate (Cys-Sgamma-SO(-)), Cys-thiosulfinate (Cys
      Sgamma-SO(2)(-)), and Cys-thiosulfonate (Cys-Sgamma-SO(3)(-)). Next, sulfur
      acceptor substrates including reduced thioredoxin convert all modified cysteines
      to nonmodified cysteines. Another sulfur acceptor substrate, cyanide, also
      converted these cysteines via cyanolysis. Thus, sulfur oxides are suggested to
      release in the redox cycle of persulfide of MST.

PMID- 22149236
TI  - Short communication: Colony-forming hematopoietic progenitor cells are not
      preferentially infected by HIV type 1 subtypes A and D in vivo.
AB  - HIV subtype C has previously been shown to infect hematopoietic progenitor cells
      (HPCs) at a significantly higher rate than subtype B. To better understand the
      subtype-specific nature of HPC infection, we examined the prevalence of HPC
      infection in vivo by HIV-1 subtypes A and D. HIV-1 infection of HPC was examined
      in 40 individuals, 19 infected with subtype A and 21 with subtype D, using a
      single colony assay format. DNA from 1177 extracted colonies was tested for
      integrated viral DNA of the p24 gene. Four colonies were found to be stably
      infected, three of 462 colonies (0.65%) from HIV-1A-infected individuals (1/19
      individuals) and one of 715 colonies (0.14%) from HIV-1D-infected individuals
      (1/22 individuals). These rates of colony infection were comparable to the rates
      observed in PBMCs from the same subjects. Additionally, no correlation was
      observed between cell colony density and circulating viral load or proviral load.
      Our findings suggest that HIV-1 subtypes A and D do not preferentially infect
      colony-forming HPCs over mature HIV target cells in vivo.

PMID- 22149237
TI  - Long-term concentrative meditation and cognitive performance among older adults.
AB  - BACKGROUND: The general consensus that cognitive abilities decline with advancing
      age is supported by several studies that have reported that older adults perform
      more poorly on multiple tests of cognitive performance as compared to younger
      adults. To date, preventive measures against this cognitive decline have been
      mainly focused on dietary, physical, and lifestyle behaviors which could allow
      older adults to maintain their cognitive abilities into late life. However, much
      less stress has been laid on evaluating meditation as a preventive measure in
      such cases in spite of the fact that the role of meditation on attention has been
      proved in several studies. In the current study, we extend this preliminary idea,
      examining the practice of concentrative meditation and the differences in the
      cognitive performance of older adults who have or have not employed this practice
      long term. METHODOLOGY: This was a cross-sectional study comparing the cognitive
      performance of meditators and non-meditators in the geriatric age group. Twenty
      (age > 55 years) long-term practitioners of Vihangam Yoga meditation (>10 years
      of practice) were recruited in the present study and were applied six paper
      pencil neuropsychological tests for assessment of short-term memory, perceptual
      speed, attention, and executive functioning. The tests used were: (1) the Digit
      Span test, (2) the Stroop Color Word test, (3) the Trailmaking test, (4) the
      Letter Cancellation Task, (5) the digit symbol substitution test, and (6) the
      Rule Shift Card Test. All the tests were also applied to 20 age- and education
      matched geriatric adults who have not practiced the meditation technique.
      RESULTS: Vihangam Yogis showed significantly better performances in all these
      tests of attention (p < .05) except for the digit backward test, where a trend (p
      = .08) was found in favor of meditators. CONCLUSION: Long-term Vihangam Yoga
      meditators have superior cognitive abilities than non-meditators in the old age
      group. This technique should be studied further for its ability to prevent age
      related cognitive decline.

PMID- 22149238
TI  - In situ characterization by SAXS of concentration polarization layers during
      cross-flow ultrafiltration of Laponite dispersions.
AB  - The structural organization inside the concentration polarization layer during
      cross-flow membrane separation process of Laponite colloidal dispersions has been
      characterized for the first time by in situ time-resolved small-angle X-ray
      scattering (SAXS). Thanks to the development of new "SAXS cross-flow filtration
      cells", concentration profiles have been measured as a function of the distance z
      from the membrane surface with 50 MUm accuracy and linked to the permeation flux,
      cross-flow, and transmembrane pressure registered simultaneously. Different
      rheological behaviors (thixotropic gel with a yield stress or shear thinning sol)
      have been explored by controlling the mutual interactions between the particles
      as a result on the addition of peptizer. The structural reversibility of the
      concentration polarization layer has been demonstrated being in agreement with
      permeation flux measurements. These observations were related to structure of the
      dispersions under flow and their osmotic pressure.

PMID- 22149250
TI  - A systematic review of psychometric evaluations of outcome assessments for
      complex regional pain syndrome.
AB  - PURPOSE: To conduct a systematic review of the quality and extent of psychometric
      examinations of disease-specific outcome measures for complex regional pain
      syndrome (CRPS). METHODS: Health database searches yielded 23 papers covering 19
      assessment instruments. Each article was scored for quality using a 12-item
      structured tool; data were also extracted for comparison of tool content.
      RESULTS: Article quality ratings ranged from 25 to 88%. Six of the tools were
      specific to the upper extremity; 5 for the lower extremities while the remaining
      8 were general. Many 'general' tools focused on a single construct, such as pain,
      skin temperature or allodynia. Most psychometric data was based on small studies
      (mean n=33); only one study addressed all relevant issues of reliability,
      validity and responsiveness. CONCLUSIONS: Despite the variety of outcome
      measurement tools reported for CRPS rehabilitation, large gaps in both
      comprehensiveness and supporting psychometric evidence remain. Comprehensive,
      relevant and psychometrically sound tools for monitoring treatment outcomes are
      needed to address the pain and functional limitations experienced by this
      population.

PMID- 22149252
TI  - Ripping graphene: preferred directions.
AB  - The understanding of crack formation due to applied stress is key to predicting
      the ultimate mechanical behavior of many solids. Here we present experimental and
      theoretical studies on cracks or tears in suspended monolayer graphene membranes.
      Using transmission electron microscopy, we investigate the crystallographic
      orientations of tears. Edges from mechanically induced ripping exhibit straight
      lines and are predominantly aligned in the armchair or zigzag directions of the
      graphene lattice. Electron-beam induced propagation of tears is also observed.
      Theoretical simulations account for the observed preferred tear directions,
      attributing the observed effect to an unusual nonmonotonic dependence of graphene
      edge energy on edge orientation with respect to the lattice. Furthermore, we
      study the behavior of tears in the vicinity of graphene grain boundaries, where
      tears surprisingly do not follow but cross grain boundaries. Our study provides
      significant insights into breakdown mechanisms of graphene in the presence of
      defective structures such as cracks and grain boundaries.

PMID- 22149253
TI  - Frequent false hearing by older adults: the role of age differences in
      metacognition.
AB  - In two experiments testing age differences in the subjective experience of
      listening, which we call meta-audition, young and older adults were first trained
      to learn pairs of semantic associates. Following training, both groups were
      tested on identification of words presented in noise, with the critical
      manipulation being whether the target item was congruent, incongruent, or neutral
      with respect to prior training. Results of both experiments revealed that older
      adults compared to young adults were more prone to "false hearing," defined as
      mistaken high confidence in the accuracy of perception when a spoken word had
      been misperceived. These results were obtained even when performance was equated
      across age groups on control items by reducing the noise level for older adults.
      Such false hearing is shown to reflect older adults' heavier reliance on context.
      Findings suggest that older adults' greater ability to benefit from semantic
      context reflects their bias to respond consistently with the context, rather than
      their greater skill in using context. Procedures employed are unique in measuring
      the subjective experience of hearing as well as its accuracy. Both theoretical
      and applied implications of the findings are discussed. Convergence of results
      with those showing higher false memory, and false seeing are interpreted as
      showing that older adults are less able to constrain their processing in ways
      that are optimal for performance of a current task. That lessened constraint may
      be associated with decline in frontal-lobe functioning.

PMID- 22149255
TI  - Vancomycin: a review of population pharmacokinetic analyses.
AB  - Despite nearly five decades of clinical use, vancomycin has retained a
      significant and uncontested niche in the antibacterial arsenal because of its
      consistent activity against almost all Gram-positive bacteria. Nevertheless,
      major vancomycin toxicities have been reported in the literature - in particular,
      nephrotoxicity and ototoxicity. Vancomycin pharmacokinetics have been described
      in numerous studies for 25 years. This review presents a synthesis of the
      reported population pharmacokinetic models of vancomycin. The objective was to
      determine if there was a consensus on a structural model and which covariates
      were identified. A literature search was conducted from the PubMed database, from
      its inception through December 2010, using the following terms: 'vancomycin',
      'pharmacokinetic(s)', 'population', 'model(ling)' and 'nonlinear mixed effect'.
      Articles were excluded if they were not pertinent. The reference lists of all
      selected articles were also evaluated. Twenty-five articles were included in this
      review: 15 models concerned paediatric patients and ten models were conducted in
      adults. In neonates and infants, the pharmacokinetics of vancomycin were mainly
      described by a one-compartment model, whereas in adults, a two-compartment model
      was preferentially used. Various covariates were tested but only three (age,
      creatinine clearance [CL(CR)] and body weight) were included in almost all of the
      described models. After inclusion of these covariates, the mean (range) values of
      the interindividual variability in the clearance and volume of distribution were
      30% (15.6-45%) and 23% (12.6-48%), respectively. The mean (range) value of the
      residual variability was 20% (7-39.6%). This review highlights the numerous
      population pharmacokinetic models of vancomycin developed in recent decades and
      concludes with relevant information for clinicians and researchers. To optimize
      vancomycin dosage, this review points out the relevant covariates according to
      the target population. In adults, dosage optimization depends on CL(CR) and body
      weight, while in children, it depends on age, body weight and CL(CR). For future
      population pharmacokinetic studies, a sensitive liquid chromatography-tandem mass
      spectrometry method could be used and new covariates such as cardiac output or
      possible renal transporters could be tested. Finally, we suggest that external
      evaluation should be the first step in a pharmacokinetic analysis of vancomycin
      rather than describing a new model.

PMID- 22149256
TI  - Clinical pharmacokinetics of fingolimod.
AB  - Fingolimod (FTY720), a sphingosine 1-phosphate receptor modulator, is the first
      in a new class of therapeutic compounds and is the first oral therapy approved
      for the treatment of relapsing forms of multiple sclerosis (MS). Fingolimod is a
      structural analogue of endogenous sphingosine and undergoes phosphorylation to
      produce fingolimod phosphate, the active moiety. Fingolimod targets MS via
      effects on the immune system, and evidence from animal models indicates that it
      may also have actions in the central nervous system. In phase III studies in
      patients with relapsing-remitting MS, fingolimod has demonstrated efficacy
      superior to that of an approved first-line therapy, intramuscular interferon-beta
      1a, as well as placebo, with benefits extending across clinical and magnetic
      resonance imaging measures. The pharmacokinetic profiles of fingolimod and
      fingolimod phosphate have been extensively investigated in studies in healthy
      volunteers, renal transplant recipients (the indication for which fingolimod was
      initially under clinical development, but the development was subsequently
      discontinued) and MS patients. Results from these studies have demonstrated that
      fingolimod is efficiently absorbed, with an oral bioavailability of >90%, and its
      absorption is unaffected by dietary intake, therefore it can be taken without
      regard to meals. Fingolimod and fingolimod phosphate have a half-life of 6-9
      days, and steady-state pharmacokinetics are reached after 1-2 months of daily
      dosing. The long half-life of fingolimod, together with its slow absorption,
      means that fingolimod has a flat concentration profile over time with once-daily
      dosing. Fingolimod and fingolimod phosphate show dose-proportional exposure in
      single- and multiple-dose studies over a range of 0.125-5 mg; hence, there is a
      predictable relationship between dose and systemic exposure. Furthermore,
      fingolimod and fingolimod phosphate exhibit low to moderate intersubject
      pharmacokinetic variability. Fingolimod is extensively metabolized, with
      biotransformation occurring via three main pathways: (i) reversible
      phosphorylation to fingolimod phosphate; (ii) hydroxylation and oxidation to
      yield a series of inactive carboxylic acid metabolites; and (iii) formation of
      non-polar ceramides. Fingolimod is largely cleared through metabolism by
      cytochrome P450 (CYP) 4F2. Since few drugs are metabolized by CYP4F2, fingolimod
      would be expected to have a relatively low potential for drug-drug interactions.
      This is supported by data from in vitro studies indicating that fingolimod and
      fingolimod phosphate have little or no capacity to inhibit and no capacity to
      induce other major drug-metabolizing CYP enzymes at therapeutically relevant
      steady-state blood concentrations. Population pharmacokinetic evaluations
      indicate that CYP3A inhibitors and CYP3A inducers have no effect or only a weak
      effect on the pharmacokinetics of fingolimod and fingolimod phosphate. However,
      blood concentrations of fingolimod and fingolimod phosphate are increased
      moderately when fingolimod is coadministered with ketoconazole, an inhibitor of
      CYP4F2. The pharmacokinetics of fingolimod are unaffected by renal impairment or
      mild-to-moderate hepatic impairment. However, exposure to fingolimod is increased
      in patients with severe hepatic impairment. No clinically relevant effects of
      age, sex or ethnicity on the pharmacokinetics of fingolimod have been observed.
      Fingolimod is thus a promising new therapy for eligible patients with MS, with a
      predictable pharmacokinetic profile that allows effective once-daily oral dosing.

PMID- 22149258
TI  - Calculation of normalized drug concentrations in the presence of altered plasma
      protein binding.
AB  - BACKGROUND AND OBJECTIVE: In many clinical situations, measurement of the total
      drug concentration does not provide the needed information concerning the
      fraction of unbound drug in plasma, which is available for pharmacodynamic
      action. To address this, a 'normalized concentration' can be calculated on the
      basis of the observed total drug concentration and the serum protein level. Up to
      now, this method has only been applied to phenytoin. Several equations for
      calculating normalized concentrations of phenytoin have been published, many
      leading to different results. Regrettably, all of the equations in the current
      literature are based on an outdated model of drug binding to human serum albumin
      and are based on the fraction of unbound drug, which is known to depend on both
      protein and drug concentrations. In response to the relatively new scientific
      evidence about drug binding to human plasma proteins, the objective of the
      present study is to develop a general method for calculating normalized drug
      concentrations in the presence of altered plasma protein binding. METHODS: When
      several drug molecules can be bound by a protein molecule, multiple equilibria
      are established; these equilibria may be formulated in terms of a stoichiometric
      analysis or a site-oriented analysis. Both models are currently encountered in
      the scientific literature, sometimes without clear identification of which model
      is used. The present study presents the basic equations for both models and shows
      how the normalized concentration can be calculated on the basis of the measured
      drug concentration, the protein level and the binding constants. RESULTS: The
      normalized concentration can be calculated for any drug, using the same simple
      equation regardless of the binding model and the number of binding proteins.
      Explicit solutions are presented for particular cases of clinical importance. The
      new model is validated by comparison with the Winter-Tozer equation for
      calculating the normalized phenytoin concentration and is found to be equivalent
      for concentrations close to therapeutic concentrations. In the case of phenytoin,
      the main advantage of the new equation is that it also works outside the linear
      binding range. CONCLUSIONS: A new comprehensive method for calculating normalized
      drug concentrations is developed, allowing drug concentrations to be interpreted
      correctly in cases of altered drug-protein binding. The calculations are based on
      binding constants and are applicable to any protein level and drug concentration,
      without being limited to linear binding of drugs to proteins. The new model is
      expected to become important in pharmacokinetic-pharmacodynamic modelling,
      allometric scaling and population pharmacokinetics because it provides the
      ability to accurately take into account physiological and pathological changes in
      protein binding. As a direct clinical application, the equations can be used to
      calculate normalized drug concentrations in patients with abnormal protein
      levels, such as the elderly, trauma patients and paediatric patients.

PMID- 22149259
TI  - Enhanced integrin mediated signaling and cell cycle progression on fibronectin
      mimetic peptide amphiphile monolayers.
AB  - In recent years, a variety of biomimetic constructs have emerged which mimic the
      bioactive sequences found in the natural extracellular matrix (ECM) proteins such
      as fibronectin (FN) that promote cell adhesion as well as proliferation on
      artificially functionalized interfaces. Much interest lies in investigating the
      ability of the ECM mimetic materials in regulating a number of vital cell
      functions including differentiation, gene expression, migration, and
      proliferation. A peptide amphiphile PR_b containing both the cell adhesive GRGDSP
      and synergistic PHSRN peptide sequences was developed in our group that was shown
      to support enhanced cell proliferation and ECM FN secretion as compared to GRGDSP
      and FN functionalized interfaces. In this study, we have investigated the binding
      affinity of the PR_b peptide ligand with the FN cell surface receptor, the
      alpha(5)beta(1) integrin. We compared PR_b functionalized surfaces with FN and
      BSA coated surfaces and GRGDSP functionalized surfaces in terms of promoting
      intracellular signaling cascades that are essential for enhanced cellular
      activity. Specifically, we studied the phosphorylation of focal adhesion kinase
      (FAK) at tyrosine residues Y397 and Y576 and the formation of cyclin D1, both of
      which are intracellular markers of integrin mediated attachment of cells,
      signaling pathways, and progression of cell cycle. FAK and cyclin D1 encourage
      enhanced cell proliferation, differentiation, and gene expression. Our results
      show that the PR_b peptide ligand has a specific and strong binding affinity for
      the alpha(5)beta(1) integrin with a dissociation constant of 76.3 +/- 6.3 nM. The
      PR_b peptide ligands supported enhanced FAK phosphorylation activity and
      increased cyclin D1 formation as compared to the widely used GRGDSP ligand, the
      native protein FN (positive control), and BSA nonadhesive surfaces (negative
      control). These results encourage the use of the FN mimetic PR_b peptide in
      functionalizing biomaterials for potential tissue engineering and therapeutic
      applications.

PMID- 22149257
TI  - A pharmacokinetic-pharmacodynamic model for predicting the impact of CYP2C9 and
      VKORC1 polymorphisms on fluindione and acenocoumarol during induction therapy.
AB  - BACKGROUND AND OBJECTIVE: Vitamin K epoxide reductase complex, subunit 1 (VKORC1)
      and cytochrome P450 2C9 (CYP2C9) polymorphisms are taken into account when
      predicting a safe oral dose of coumarin anticoagulant therapy, but little is
      known about the effects of genetic predictors on the response to fluindione and
      acenocoumarol. The aims of this study were to characterize the relationship
      between fluindione and acenocoumarol concentrations and the international
      normalized ratio (INR) response, and to identify genetic predictors that are
      important for dose individualization. METHODS: Fluindione concentrations, S- and
      R-acenocoumarol concentrations, the INR and genotype data from healthy subjects
      were used to develop a population pharmacokinetic-pharmacodynamic model in
      Monolix software. Twenty-four White healthy subjects were enrolled in the
      pharmacogenetic study. The study was an open-label, randomized, two-period cross
      over study. The subjects received two doses of an oral anticoagulant: 20 mg of
      fluindione (period A) or 4 mg of acenocoumarol (period B). The pharmacokinetics
      and pharmacodynamics were studied from day 2 to day 3. RESULTS: A two-compartment
      model with a first-order input model was selected as the base model for the two
      drugs. The pharmacodynamic response was best described by an indirect action
      model with S-acenocoumarol concentrations and fluindione concentrations as the
      only exposure predictors of the INR response. Three covariates (CYP2C9 genotype,
      VKORC1 genotype and body weight) were identified as important predictors for the
      pharmacokinetic-pharmacodynamic model of S-acenocoumarol, and four covariates
      (CYP2C9 genotype, VKORC1 genotype, CYP1A2 phenotype and body weight) were
      identified as predictors for the pharmacokinetic-pharmacodynamic model of
      fluindione. Because some previous studies have shown a dose-response relationship
      between smoking exposure and the CYP1A2 phenotype, it was also noted that smokers
      have greater CYP1A2 activity. CONCLUSION: During initiation of therapy, CYP2C9
      and VKORC1 genetic polymorphisms are important predictors of fluindione and
      acenocoumarol pharmacokinetic-pharmacodynamic responses. Our result suggests that
      it is important to take the CYP1A2 phenotype into account to improve
      individualization of fluindione therapy, in addition to genetic factors.

PMID- 22149260
TI  - Anti-TNF trough levels and detection of antibodies to anti-TNF in inflammatory
      bowel disease: are they ready for everyday clinical use?
AB  - INTRODUCTION: In the last two decades, with the development of biological (anti
      TNFalpha) therapy, the treatment paradigms for Crohn's disease and ulcerative
      colitis have evolved, with a continuously increasing role of biologicals. Some
      patients, however, experience lack- or loss of response (LOR) to treatment, and
      management of such patients is often empirical. AREAS COVERED: The available data
      regarding the relationship between serum anti-TNF concentrations, antibodies
      against anti-TNF agents, and clinical efficacy, as well as the development of
      adverse events and management of LOR. EXPERT OPINION: Monitoring drug levels and
      antibodies is expected to play an emerging role in the management of LOR (i.e.,
      to confirm adherence, allow for dose adjustment, or provide a rationale for
      switching to another anti-TNF agent or to a different class of biological agent)
      in the coming years. The optimal method of detection is however not clear. In
      clinical practice, meticulous complex assessment of clinical symptoms,
      confirmation of active disease by endoscopic or radiological imaging, and
      exclusion of complications remains necessary.

PMID- 22149261
TI  - Computational prediction of microRNAs and their targets from three unicellular
      algae species with complete genome sequences.
AB  - The genome sequences of Phaeodactylum tricornutum, Thalassiosira pseudonana, and
      Cyanidioschyzon merolae have provided significant evidence for the secondary
      endosymbiosis of diatoms in regard to the genome. Yet little about their
      relationships in regard to gene regulation pattern, such as microRNA (miRNA), has
      been reported. Using a homology search based on genomic sequences, 13, 3, and 7
      predicted miRNA genes were found in genomes from P. tricornutum, T. pseudonana,
      and C. merolae, respectively. Of the 23 miRNA genes, 18 had homology with animal
      miRNAs, implying that they are ancestral miRNAs. A phylogenetic tree based on
      common miRNA families shared by these three unicellular algae, higher plants, and
      animals showed that P. tricornutum shared most miRNAs with animals. The
      phylogenetic tree also showed that C. merolae shared more miRNAs with plants than
      did the two diatoms, and the majority of its miRNAs were shared with the two
      diatoms. Our results were consistent with diatoms originating from a secondary
      endosymbiosis.

PMID- 22149264
TI  - AgNOR, p16 and human papillomavirus in low-grade squamous intra-epithelial
      lesions of the uterine cervix. Preliminary report.
AB  - It has been shown that infection with high-risk human papillomaviruses (HR-HPV)
      is related to the development of cervical cancer. The persistence of the virus in
      intra-epithelial lesions of cervix uteri (SILs) is the basis for the application
      of HPV testing for screening and management of patients. Most infections by HR
      HPVs resolve spontaneously, however, and do not progress to dysplasia or cancer.
      p16INK4a is a useful biomarker of cervical intra-epithelial neoplasia and could
      be a marker for the progression of low-grade squamous intra-epithelial lesions
      (LSILs) to high-grade squamous intra-epithelial lesions (HSILs), because it
      correlates independently with increasing SIL grade. We conducted a preliminary
      histological study of 28 patients diagnosed with LSIL, HSIL or nondysplastic
      epithelium (NDE) from whom 28 biopsies of uterine cervix and 28 endocervical
      brushed biopsies were taken. Argyrophilic nucleolar organizer region (AgNOR) and
      p16INK4a assays were performed on the biopsies, and endocervical brushings were
      used for HPV typing. The high risk HPV group showed that the number of patients
      with AgNOR areas greater than 3.3 um(2) and with expression of p16INK4a were
      statistically greater than the number of lower risk patients. None of the
      biopsies of LR-HPV carriers expressed p16 and AgNOR areas> 3.3 MUm(2)
      simultaneously. Four LSILs and the NDE of this group expressed neither of the two
      markers. If the correlation between AgNOR areas and p16INK4a is good, we may be
      able to develop a low cost simple technology for studying patients infected with
      HR-HPV and diagnosed with LSIL of uncertain behavior.

PMID- 22149265
TI  - Plasmodium knowlesi: a malaria parasite of monkeys and humans.
AB  - Plasmodium knowlesi is a malaria parasite of monkeys of Southeast Asia that is
      transmitted by mosquitoes of the Anopheles leucosphyrus group. Humans are
      frequently infected with this parasite and misdiagnosed as being infected with
      Plasmodium malariae. The parasite was a major monkey animal model for developing
      antimalarial vaccines and investigations of the biology of parasite invasion. P.
      knowlesi is the first monkey malaria parasite genome to be sequenced and
      annotated.

PMID- 22149266
TI  - Insect transgenesis: current applications and future prospects.
AB  - The ability to manipulate the genomes of many insects has become a practical
      reality over the past 15 years. This has been led by the identification of
      several useful transposon vector systems that have allowed the identification and
      development of generalized, species-specific, and tissue-specific promoter
      systems for controlled expression of gene products upon introduction into insect
      genomes. Armed with these capabilities, researchers have made significant strides
      in both fundamental and applied transgenics in key model systems such as Bombyx
      mori, Tribolium casteneum, Aedes aegypti, and Anopheles stephensi. Limitations of
      transposon systems were identified, and alternative tools were developed, thus
      significantly increasing the potential for applied transgenics for control of
      both agricultural and medical insect pests. The next 10 years promise to be an
      exciting time of transitioning from the laboratory to the field, from basic
      research to applied control, during which the full potential of gene manipulation
      in insect systems will ultimately be realized.

PMID- 22149267
TI  - Systematics, biodiversity, biogeography, and host associations of the Miridae
      (Insecta: Hemiptera: Heteroptera: Cimicomorpha).
AB  - The Miridae, a hyperdiverse family containing more than 11,020 valid described
      species, are discussed and the pertinent literature is reviewed. Diagnoses for
      the family and subfamilies are given. Color habitus photos are presented for
      representatives of most of the 35 currently recognized tribes. Key morphological
      character systems are discussed and illustrated, including pretarsal structures,
      femoral trichobothria, external efferent system of the metathoracic glands, male
      and female genitalia, and molecular markers. A historical comparison of tribal
      classifications and the most up-to-date classification are presented in tabular
      form. A brief history of the classification of each of the eight recognized
      subfamilies is presented. Distributional patterns and relative generic diversity
      across biogeographic regions are discussed; generic diversity by biogeographic
      region is presented in tabular form. Taxonomic accumulation graphs are presented
      by biogeographic region, indicating an ongoing need for taxonomic work in the
      Southern Hemisphere, and most particularly in Australia. Host plant associations
      are evaluated graphically, showing high specificity for many taxa and a
      preference among phytophagous taxa for the Asteridae and Rosidae.

PMID- 22149268
TI  - Key aspects of the biology of snail-killing Sciomyzidae flies.
AB  - The biology of snail-killing flies (Diptera: Sciomyzidae) has been studied
      intensively over the past half-century, especially over the past decade. Today,
      sciomyzids are biologically the best-known group of higher Diptera. The
      overarching research objectives are evaluation of sciomyzids as biocontrols of
      disease-carrying or agriculturally important snails and slugs and as a paradigm
      group for the study of the evolution of diverse feeding and associated behaviors
      in flies. We present reviews and analyses of some key features of particular
      scientific and societal interest, including behavioral and phenological groups;
      laboratory experimental studies on behavior and development; population biology,
      bioindicators, ecosystem service provision, and conservation; phylogenetics,
      molecular studies, and evolutionary biology; and biocontrol.

PMID- 22149269
TI  - Advances in insect phylogeny at the dawn of the postgenomic era.
AB  - Most species on Earth are insects and thus, understanding their evolutionary
      relationships is key to understanding the evolution of life. Insect relationships
      are increasingly well supported, due largely to technological advances in
      molecular sequencing and phylogenetic computational analysis. In this postgenomic
      era, insect systematics will be furthered best by integrative methods aimed at
      hypothesis corroboration from molecular, morphological, and paleontological
      evidence. This review of the current consensus of insect relationships provides a
      foundation for comparative study and offers a framework to evaluate incoming
      genomic evidence. Notable recent phylogenetic successes include the resolution of
      Holometabola, including the identification of the enigmatic Strepsiptera as a
      beetle relative and the early divergence of Hymenoptera; the recognition of
      hexapods as a crustacean lineage within Pancrustacea; and the elucidation of
      Dictyoptera orders, with termites placed as social cockroaches. Regions of the
      tree that require further investigation include the earliest winged insects
      (Palaeoptera) and Polyneoptera (orthopteroid lineages).

PMID- 22149270
TI  - N-Heterocyclic carbene boranes are good hydride donors.
AB  - The nucleophilicity parameters (N) of 1,3-bis(2,6-diisopropylphenyl)imidazol-2
      ylidene borane and 1,3-dimethylimidazol-2-ylidene borane are 9.55 and 11.88. This
      places N-heterocyclic carbene boranes (NHC-boranes) among the most nucleophilic
      classes of neutral hydride donors. Reductions of highly electron-poor C?N and C?C
      bonds provide hydrogenation products along with new, stable borylated products.
      The results suggest that NHC-boranes have considerable untapped potential as
      neutral organic reductants.

PMID- 22149271
TI  - Treatment of severe hypertriglyceridemia associated with accidental pegylated
      asparaginase push in a child with relapsed acute lymphoblastic leukemia.
AB  - Asparaginase treatment is associated with several adverse effects, including
      allergy, thromboembolic events, acute pancreatitis, altered liver function, and
      hyperglycemia. In addition, asparaginase can cause abnormalities in lipid
      metabolism, predominantly hypercholesterolemia and -triglyceridemia. Herein, we
      report on the case of a 5-year-old male presenting with acute severe
      hypertriglyceridemia caused by accidental pegylated asparaginase push during
      treatment of relapsed acute lymphoblastic leukemia. Hypertriglyceridemia did not
      occur after appropriate administrations of pegylated asparaginase before and
      after accidental drug infusions, so we speculate that the rate of pegylated
      asparaginase administration may have an effect on the serum triglyceride level.

PMID- 22149272
TI  - SIRT1 and the clock gene machinery in colorectal cancer.
AB  - SIRT1 and the clock genes are involved in carcinogenesis. We evaluated SIRT1
      expression in 19 human colorectal cancer (CRC) specimens and clock gene
      expression in SIRT1-overexpressing CaCo2 and SW480 cells. In CRC, SIRT1 mean
      expression level was decreased. Compared to CaCo2 cells, SW480 cells displayed
      lower levels of SIRT1 and PER3 and higher levels of ARNTL1, CLOCK, PER1, PER2,
      CRY1, TIPIN, and CSNKIE. SIRT1 overexpression induced PER1 upregulation in CaCo2
      and downregulation in SW480 cells. SIRT1 expression was heterogeneous in human
      CRC and in CRC cell lines. These results might have relevant implications for a
      better understanding of colorectal carcinogenesis.

PMID- 22149273
TI  - Serum proteins prevent aggregation of Fe2O3 and ZnO nanoparticles.
AB  - Aggregation of metal oxide nanoparticles in aqueous media complicates
      interpretation of in vitro studies of nanoparticle-cell interactions. We used
      dynamic light scattering to investigate the aggregation dynamics of iron oxide
      and zinc oxide nanoparticles. Our results show that iron oxide particles
      aggregate more readily than zinc oxide particles. Pretreatment with serum
      stabilises iron oxide and zinc oxide nanoparticles against aggregation. Serum
      treated iron oxide is stable only in pure water, while zinc oxide is stable in
      water or cell culture media. These findings, combined with zeta potential
      measurements and quantification of proteins adsorbed on particle surface, suggest
      that serum stabilisation of iron oxide particles occurs primarily through protein
      adsorption and resulting net surface charge. Zinc oxide stabilisation, however,
      also involves steric hindrance of particle aggregation. Fluid shear at levels
      used in flow experiments breaks up iron oxide particle aggregates. These results
      enhance our understanding of nanoparticle aggregation and its consequences for
      research on the biological effects of nanomaterials.

PMID- 22149275
TI  - Specific targeting of Ep-CAM in various carcinomas by novel monoclonal
      antibodies.
AB  - Epithelial cell adhesion molecule (Ep-CAM) is a 40 kDa transmembrane glycoprotein
      overexpressed in majority of tumor epithelial cells and has a major
      morphoregulatory function, relevant not only to epithelial tissue development,
      but also in carcinogenesis and tumor progression. Since Ep-CAM localizes at the
      cell surface of most carcinomas, the molecule is an attractive target for
      immunotherapy and several strategies have been deployed to treat cancer using Ep
      CAM targeting, including MAb therapy. For improving effective targeting of this
      protein for diagnostics in various clinical samples, we generated and
      characterized an anti-Ep-CAM MAb (C4) using recombinant Ep-CAM protein,
      comprising the highly immunogenic domain. The specificity of C4-MAb was
      characterized in Ep-CAM positive cell lines (PC3 and MCF-7) by flow cytometry and
      immunofluorescence. The immunohistochemistry analysis in clinical tissue samples
      showed specific detection of epithelial antigens in breast, colon, stomach, and
      prostate carcinomas. Thus, this Ep-CAM MAb (C4-MAb) could be used for both
      diagnostic and therapeutic applications due to its specificity.

PMID- 22149274
TI  - Epitope characterization of sero-specific monoclonal antibody to Clostridium
      botulinum neurotoxin type A.
AB  - Botulinum neurotoxins (BoNTs) are extremely potent toxins that can contaminate
      foods and are a public health concern. Anti-BoNT antibodies have been described
      that are capable of detecting BoNTs; however there still exists a need for
      accurate and sensitive detection capabilities for BoNTs. Herein, we describe the
      characterization of a panel of eight monoclonal antibodies (MAbs) generated to
      the non-toxic receptor-binding domain of BoNT/A (H(C)50/A) developed using a high
      throughput screening approach. In two independent hybridoma fusions, two groups
      of four IgG MAbs were developed against recombinant H(C)50/A. Of these eight,
      only a single MAb, F90G5-3, bound to the whole BoNT/A protein and was
      characterized further. The F90G5-3 MAb slightly prolonged time to death in an in
      vivo mouse bioassay and was mapped by pepscan to a peptide epitope in the N
      terminal subdomain of H(C)50/A (H(CN)25/A) comprising amino acid residues
      (985)WTLQDTQEIKQRVVF(999), an epitope that is highly immunoreactive in humans.
      Furthermore, we demonstrate that F90G5-3 binds BoNT/A with nanomolar efficiency.
      Together, our results indicate that F90G5-3 is of potential value as a diagnostic
      immunoreagent for BoNT/A capture assay development and bio-forensic analysis.

PMID- 22149276
TI  - Monoclonal antibodies against recombinant histidine-rich protein 2 of Plasmodium
      falciparum and their use in malaria diagnosis.
AB  - Histidine-rich protein-2 (HRPII) secreted by Plasmodium falciparum finds its use
      as a compelling marker in malaria diagnosis and follow-up. Monoclonal antibodies
      (MAbs) against P. falciparum HRPII are widely used in antibody-based diagnostic
      systems to detect HRPII protein in blood of malaria-suspected individuals. In
      this study, a set of five monoclonal antibodies against recombinant HRPII
      (rHRPII) were generated and assessed for their potential in diagnostics. Three
      among the five generated MAbs were of IgG1 isotype and the remaining were of IgM
      isotype. Probing the MAbs against proved P. falciparum infected serum and pooled
      control sera by immunoblotting revealed that the MAbs were successful in exposing
      malarial infection. Collectively, the generated MAbs have the potential to be
      used in immuno-based diagnostic systems uncovering P. falciparum infections.

PMID- 22149277
TI  - Expression of the PreS1 peptide of hepatitis B virus and preparation of its
      polyclonal antibody.
AB  - PreS1 is a hypothetical candidate domain of L protein for hepatitis B virus (HBV)
      to adhere to and invade host hepatic cells. This report deals with the expression
      and purification of recombinant adw2 subtype of the preS1 peptide of hepatitis B
      virus surface antigen in Escherichia coli. The DNA fragments of the full-length
      or N/C terminal sequence of preS1 synthesized by PCR were inserted into the
      prokaryotic expression vector pGST-MOLUC, respectively. Reconstitute plasmids
      (named pGST-preS1, pGST-preS1N, and pGST-preS1C) were confirmed by sequencing
      analysis and transferred into Escherichia coli BL21(DE3). Recombinant full-length
      and N/C terminal of preS1 with GST tag were expressed at high levels in soluble
      form after induction with IPTG. The recombinant proteins were purified by a
      single-step affinity chromatography method. The immune reactivity of recombinant
      preS1 was confirmed by Western blot and virus capture assay. Furthermore, when
      the purified recombinant protein was used to immunize rabbit, the specific
      antibody titer can reach 10(-7). Thus, our successful expression system and
      achievement of purified recombinant preS1 protein and its polyclonal antibody lay
      the foundation for better understanding of the mechanism of HBV PreS1 protein in
      virus endocytosis and are helpful in seeking the PreS1-related protein.

PMID- 22149278
TI  - A monoclonal antibody against the oncogenic mucin 1 cytoplasmic domain.
AB  - Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly overexpressed in
      diverse human carcinomas and certain hematologic malignancies. The transmembrane
      MUC1-C subunit confers tumorigenicity and is a target for anti-cancer drug
      development. In this regard, the MUC1-C cytoplasmic domain interacts with
      multiple effectors that have been linked to transformation. Here we report on the
      generation of a mouse monoclonal antibody (MAb) against the human MUC1-C
      cytoplasmic domain (MUC1-CD). This IgG1 MAb, designated anti-MUC1-CD, reacts with
      the NYGQLDIFP epitope. We show that anti-MUC1-CD is useful in immunoblotting and
      immunoprecipitation experiments. In addition, anti-MUC1-CD can be used to detect
      expression of the MUC1-C subunit in formalin-fixed, paraffin-embedded tissues.
      The MUC1-C inhibitor has entered Phase I evaluation for patients with refractory
      solid tumors. The present results indicate that the anti-MUC1-CD antibody could
      be useful as a biomarker to identify patients with tumors that may be responsive
      to MUC1-C inhibitors.

PMID- 22149279
TI  - A mouse monoclonal antibody against the gamma2 subunit of GABAA receptors.
AB  - A mouse monoclonal antibody directed against the N terminal extracellular epitope
      of rat gamma amino butyric acid (GABA) type-A (GABA(A)R) receptor gamma2 subunit
      was generated. This antibody identified a protein of approximately 42 kDa in
      Western blot assays using rat and mouse hippocampal proteins. The antibody also
      detected the expression of gamma2 subunit by immunohistochemistry and could
      immunoprecipitate the gamma2 subunit.

PMID- 22149281
TI  - An anti-human ppGalNAcT-2 monoclonal antibody.
AB  - Aberrant mucin O-glycosylation is a pathological alteration that is widespread in
      cancer. The UDP-N-acetyl-D-galactosamine polypeptide N
      acetylgalactosaminyltransferases (ppGalNAc-T) family of enzymes regulates the
      initial key steps of mucin O-glycosylation. ppGalNAc-T2, as a member of the
      ppGalNAc-T family, was recently described as an altered expression in oral
      squamous cell carcinoma and colorectal and breast carcinoma. In order to gain
      further insight into the role of ppGalNAc-T2, we produced the anti-human ppGalNAc
      T2 monoclonal antibody (MAb) 5F3. The IgM kappa isotype of this MAb was further
      characterized using ELISA, Western blot analysis, flow cytometry, and
      immunofluorescent staining. In the present study, MAb 5F3 can specifically
      recognize human ppGalNAc-T2 protein in various formats by Western blot analysis,
      flow cytometry, and immunofluorescent staining. For the first time, it was shown
      that both Jurkat and HepG2 cell lines clearly express ppGalNAc-T2.

PMID- 22149282
TI  - Generation and characterization of monoclonal antibodies against channel catfish
      virus.
AB  - Three monoclonal antibodies (MAbs) against channel catfish virus (CCV) were
      generated from mice immunized with purified CCV. Western blot analysis revealed
      that the MAb 3G12 reacted with three CCV proteins of 94 kDa, 130 kDa, and 170
      kDa; the MAb 4C4 reacted with two CCV proteins of 130 kDa and 170 kDa; and the
      MAb 4D4 reacted with two CCV proteins of 94 kDa and 98 kDa. Indirect
      immunofluorescence assay showed intense fluorescence in the CCV-infected channel
      catfish ovary (CCO) cells in areas corresponding to the location of granular
      structures. In addition, the three MAbs could completely neutralize CCV at a
      dilution of 1:500. This study demonstrated that these MAbs could recognize CCV
      specifically and will be useful in the development of diagnostic methods for the
      detection of fish CCV infection.

PMID- 22149280
TI  - A humanized single-chain variable fragment antibody against beta3 integrin in
      Escherichia coli.
AB  - Patients with HIV-1 immune-related thrombocytopenia (HIV-1-ITP) have a unique
      antibody (Ab) against platelet GPIIIa49-66, which is capable of inducing
      oxidative platelet fragmentation in the absence of complement activation. By
      screening a human phage antibody library with the GPIIIa49-66 peptide as bait, we
      have developed several humanized phage Abs, which act similarly to the parental
      Ab. However, the presence of a stop codon in the heavy chain of the obtained
      phage clones limits their expression in soluble recombinant form. To circumvent
      this problem, we mutated the stop codon inside clone 11 that exhibits the highest
      binding activity to platelet GPIIIa49-66, resulting in a soluble scFv format
      (named A11) in Escherichia coli Rosseta. In in vitro binding assay, A11 exhibited
      similar binding specificity to parental Ab at various concentrations. Moreover,
      A11 is able to induce oxidative platelet fragmentation by preferentially binding
      to activated versus resting platelets. These findings provide a proof-of
      principle for the development of a novel approach to inhibit arterial thrombosis
      by generating a selective scFv for the lysis of platelet-rich thrombi.

PMID- 22149283
TI  - Novel immunohistochemical monoclonal antibody against human glucose-regulated
      protein 78.
AB  - Glucose-regulated protein (GRP78), an ER chaperone that belongs to the heat-shock
      protein (HSP) family, exist in all cells and plays important roles in maintaining
      cellular homeostasis. GRP78 participates in protein folding, transportation, and
      degradation. Lack of high affinity antibodies especially monoclonal antibodies
      (MAbs) suitable for Western blot and immunohistochemical staining has lagged. To
      gain further insight into its possible functions, we generated a novel MAb
      specific for hGRP78 in Western blot and immunohistochemistry and localized hGRP78
      in some human cancer cell lines and cancer tissues. Immunoreactivity of GRP78 was
      prominent in Hela, Colo205, and A549 detected by 3F9 in Western blot analysis.
      3F9 antibody recognized endogenous GRP78 in human cervical cancer, colonic
      cancer, esophageal cancer, and lung cancer. Thus, successful production of GRP78
      monoclonal antibodies provides a new powerful tool for investigation of GRP78
      function.

PMID- 22149284
TI  - Monoclonal antibodies against avian selenoprotein W.
AB  - The Sel-W gene encoding avian selenoprotein W was cloned into the vector pGEX-6p
      1 with GST tag. The recombinant protein Sel-W was expressed in Escherichia coli
      BL21 (DE3) after induction with 1 mM IPTG. Female 10-week-old BALB/c mice were
      immunized with the purified Sel-W recombinant protein emulsified in Freund's
      adjuvant. Two monoclonal antibodies against the Sel-W, 1B8 and 4H5, were produced
      by lymphocyte hybridoma technique. Subtypes of the MAbs 1B8 and 4H5 were all IgM,
      and their ascitic fluid titers were 1:2800 and 6400, respectively. In
      specificity, the MAbs 1B8 and 4H5 showed positive reaction with the recombinant
      Sel-W protein with GST tag and the synthesized Sel-W protein, and could not react
      with the GST tag and the recombinant Sel-N protein. In sensitivity, the detection
      limits of the MAbs 1B8 and 4H5 for the recombinant Sel-W protein and the
      synthesized Sel-W protein were 39 ng/mL and 52 ng/mL, respectively. These data
      suggest that the MAb 1B8 and 4H5 will have a potential use for detection and
      function analysis of the avian Sel-W.

PMID- 22149285
TI  - A polyclonal antibody against active C-terminal ADAMTS-18 fragment.
AB  - The human ADAMTS-18, a disintegrin and metalloproteinase with thrombospondin type
      1 modules 18, is a secreted Zn-metalloproteinase. The C-terminal 385-amino acid
      fragment of ADAMTS-18 (AD18C) is highly effective at promoting platelet thrombus
      dissolution in vivo. Therefore, polyclonal antibody (pAb) against AD18C fragment
      should be able to keep platelet thrombus stability, which has direct clinical
      relevance. In this report, pAb against AD18C fragment was generated from rabbit
      immunized with AD18C recombinant protein (rAD18C). The pAb showed specific
      binding with rAD18C and natural ADAMTS-18 protein by ELISA and Western blot
      assay. It shortens the mouse tail bleeding time in a dose-dependent manner. Thus,
      anti-AD18C pAb contributes to the regulation of platelet thrombus stability.

PMID- 22149289
TI  - Development of high-quality hexahedral human brain meshes using feature-based
      multi-block approach.
AB  - The finite element (FE) method is a powerful tool to study brain injury that
      remains to be a critical health concern. Subject/patient-specific FE brain models
      have the potential to accurately predict a specific subject/patient's brain
      responses during computer-assisted surgery or to design subject-specific helmets
      to prevent brain injury. Unfortunately, efforts required in the development of
      high-quality hexahedral FE meshes for brain, which consists of complex
      intracranial surfaces and varying internal structures, are daunting. Using multi
      block techniques, an efficient meshing process to develop all-hexahedral FE brain
      models for an adult and a paediatric brain (3-year old) was demonstrated in this
      study. Furthermore, the mesh densities could be adjusted at ease using block
      techniques. Such an advantage can facilitate a mesh convergence study and allows
      more freedom for choosing an appropriate brain mesh density by balancing
      available computation power and prediction accuracy. The multi-block meshing
      approach is recommended to efficiently develop 3D all-hexahedral high-quality
      models in biomedical community to enhance the acceptance and application of
      numerical simulations.

PMID- 22149290
TI  - Effect of dehydration on the interfacial water structure at a charged polymer
      surface: negligible chi(3) contribution to sum frequency generation signal.
AB  - Interfacial water structure at charged surfaces plays a key role in many
      physical, chemical, biological, environmental, and industrial processes.
      Understanding the release of interfacial water from the charged solid surfaces
      during dehydration process may provide insights into the mechanism of protein
      folding and the nature of weak molecular interactions. In this work, sum
      frequency generation vibrational spectroscopy (SFG-VS), supplemented by quartz
      crystal microbalance (QCM) measurements, has been applied to study the
      interfacial water structure at polyelectrolyte covered surfaces. Poly[2
      (dimethylamino)ethyl methacrylate] (PDMAEMA) chains are grafted on solid surfaces
      to investigate the change of interfacial water structure with varying surface
      charge density induced by tuning the solution pH. At pH <= 7.1, SFG-VS intensity
      is linear to the loss of mass of interfacial water caused by the dehydration of
      PDMAEMA chains, and no reorientation of the strongly bonded water molecules is
      observed in the light of chi(ppp)/chi(ssp) ratio. chi((3)) contribution to SFG
      signal is deduced based on the combination of SFG and QCM results. It is the
      first direct experimental evidence to reveal that the chi((3)) has a negligible
      contribution to SFG signal of the interfacial water at a charged polymer surface.

PMID- 22149291
TI  - Mental contrasting of a dieting wish improves self-reported health behaviour.
AB  - Mentally contrasting a desired future with present reality standing in its way
      promotes commitment to feasible goals, whereas mentally indulging in a desired
      future does not. Dieting students (N = 134) reported their most important dieting
      wish that they deemed attainable within a 2-week period. Then, they were directed
      to mentally contrast or indulge in thoughts and images about the named dieting
      wish. A control condition was given no directions. Two weeks after the
      experiment, dieters retrospectively rated their behaviour change: in the mental
      contrasting condition they reported having eaten relatively fewer calories
      overall, fewer high-calorie food and more low-calorie food compared to those in
      the indulging and control conditions, and they also reported having been more
      physically active. This transfer effect from one health domain to another
      suggests a more generalised effect of mental contrasting versus indulging and
      control than previously assumed.

PMID- 22149292
TI  - Does insulin bolster antioxidant defenses via the extracellular signal-regulated
      kinases-protein kinase B-nuclear factor erythroid 2 p45-related factor 2 pathway?
AB  - Oxidative stress plays a fundamental role in the development of diabetes, which
      has become a great threaten for health in the whole world. In recent years, it
      has been found that, in addition to the effect on metabolism, insulin plays an
      antioxidant role. However, the effect of insulin on the whole antioxidant enzyme
      system, especially in vivo, is not completely understood. We note that, in vitro
      and in vivo, insulin administration could sequentially and transiently increase a
      battery of antioxidant enzymes through the activation of the key transcription
      factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2). The sequential
      activation of extracellular signal-regulated kinases (ERK)-protein kinase B (Akt)
      pathway maybe required for insulin-induced enhancement of antioxidant defense
      regulated by Nrf2. Our observation leads to the hypothesis that insulin regulates
      the redox balance and insulin bolsters antioxidant defenses via the ERK-Akt-Nrf2
      pathway.

PMID- 22149293
TI  - A comparison of different feature extraction methods for diagnosis of valvular
      heart diseases using PCG signals.
AB  - This article presents a novel method for diagnosis of valvular heart disease
      (VHD) based on phonocardiography (PCG) signals. Application of the pattern
      classification and feature selection and reduction methods in analysing normal
      and pathological heart sound was investigated. After signal preprocessing using
      independent component analysis (ICA), 32 features are extracted. Those include
      carefully selected linear and nonlinear time domain, wavelet and entropy
      features. By examining different feature selection and feature reduction methods
      such as principal component analysis (PCA), genetic algorithms (GA), genetic
      programming (GP) and generalized discriminant analysis (GDA), the four most
      informative features are extracted. Furthermore, support vector machines (SVM)
      and neural network classifiers are compared for diagnosis of pathological heart
      sounds. Three valvular heart diseases are considered: aortic stenosis (AS),
      mitral stenosis (MS) and mitral regurgitation (MR). An overall accuracy of 99.47%
      was achieved by proposed algorithm.

PMID- 22149294
TI  - Fluorescent cream used as an educational intervention to improve the
      effectiveness of self-application by patients with atopic dermatitis.
AB  - OBJECTIVES: The aim of the study was to assess if a fluorescent cream, in a self
      application educational session, could increase the effectiveness of cream
      application in practice and serve as a therapeutic intervention. METHODS: 30
      adults with atopic dermatitis were enrolled. They applied a fluorescent test
      cream on two occasions. Effectiveness of application was checked under
      ultraviolet illumination. At baseline, the patients greased their skin as they
      normally do. After 2 weeks, the patients were instructed to grease the whole body
      area. The results were commented on and visualised to the patients on both
      occasions. RESULTS: At the baseline visit, 29% of the target skin was untreated,
      and at the follow-up visit after education, this improved to 13.6% (mean values,
      p < 0.05). Women performed better than men at baseline; however, men performed
      similar to women at the follow-up visit. CONCLUSIONS: The Fluorescent-cream
      Educational Session (FES) is an educational instrument for therapeutic
      intervention based on interaction between patient and provider. It includes hard
      endpoints, that is, visualisation and measurement of treated area, time spend on
      treatment and amount of cream used.

PMID- 22149295
TI  - Origins of thermodynamically stable superhydrophobicity of boron nitride
      nanotubes coatings.
AB  - Superhydrophobic surfaces are attractive as self-cleaning protective coatings in
      harsh environments with extreme temperatures and pH levels. Hexagonal phase boron
      nitride (h-BN) films are promising protective coatings due to their extraordinary
      chemical and thermal stability. However, their high surface energy makes them
      hydrophilic and thus not applicable as water repelling coatings. Our recent
      discovery on the superhydrophobicity of boron nitride nanotubes (BNNTs) is thus
      contradicting with the fact that BN materials would not be hydrophobic. To
      resolve this contradiction, we have investigated BNNT coatings by time-dependent
      contact angle measurement, thermogravimetry, IR spectroscopy, and electron
      microscopy. We found that the wettability of BNNTs is determined by the packing
      density, orientation, length of nanotubes, and the environmental condition. The
      origins of superhydrophobicity of these BNNT coatings are identified as (1)
      surface morphology and (2) hydrocarbon adsorbates on BNNTs. Hydrocarbon molecules
      adsorb spontaneously on the curved surfaces of nanotubes more intensively than on
      flat surfaces of BN films. This means the surface energy of BNNTs was enhanced by
      their large curvatures and thus increased the affinity of BNNTs to adsorb
      airborne molecules, which in turn would reduce the surface energy of BNNTs and
      make them hydrophobic. Our study revealed that both high-temperature and UV-ozone
      treatments can remove these adsorbates and lead to restitution of hydrophilic BN
      surface. However, nanotubes have a unique capability in building a hydrophobic
      layer of adsorbates after a few hours of exposure to ambient air.

PMID- 22149308
TI  - Effect of nanointegration on photoinduced hydrogen-generating nanogel systems.
AB  - The nanointegration mechanism for photoinduced hydrogen nanogenerators using
      nanogels is described. By spatially integrating poly(N-isopropylacrylamide-co
      Ru(bpy)(3)) nanogels as a photosensitizer and Pt nanoparticles as a catalyst, a
      mechanism using electrostatic interactions and the shrinking behavior of the
      thermosensitive polymer network is revealed. In addition, to evaluate the
      sensitivity to exterior energy, light, and heat, the integrated nanospace is
      controlled by using thermosensitive nanogels, which drastically shrink above the
      volume phase transition temperature. Such nanospatial control of multiple kinds
      of functional molecules in a photochemical reaction is important for the
      realization of artificial photosynthetic systems.

PMID- 22149307
TI  - Short communication: High prevalence of transmitted antiretroviral drug
      resistance among newly HIV type 1 diagnosed adults in Mombasa, Kenya.
AB  - Abstract   In view of the recent antiretroviral therapy (ART) scale-up in Kenya,
      surveillance of transmitted HIV drug resistance (TDR) is important. A cross
      sectional survey was conducted among newly HIV-1 diagnosed, antiretroviral-naive
      adults in Mombasa, Kenya. Surveillance drug resistance mutations (SDRMs) were
      identified according to the 2009 WHO list. HIV-1 subtypes were determined using
      REGA and SCUEAL subtyping tools. Genotypic test results were obtained for 68 of
      81 participants, and SDRMs were identified in 9 samples. Resistance to
      nonnucleoside reverse transcriptase inhibitors (K103N) occurred in five
      participants, yielding a TDR prevalence of 7.4% (95% confidence interval 2.4
      16.3%). Frequencies of HIV-1 subtypes were A (70.6%), C (5.9%), D (2.9%), and
      unique recombinant forms (20.6%). The TDR prevalence found in this survey is
      higher than previously reported in different regions in Kenya. These findings
      justify increased vigilance with respect to TDR surveillance in African regions
      where ART programs are scaled-up in order to inform treatment guidelines.

PMID- 22149309
TI  - Effect of inter-renal aortic coarctation-induced hypertension on function and
      expression of vascular alpha(1A)- and alpha(1D)-adrenoceptors.
AB  - We investigated the effect of inter-renal aortic coarctation on the function and
      expression of vascular alpha(1A)- and alpha(1D)-adrenoceptors and plasma
      angiotensin II (ATII) in rats. Male Wistar rats, either sham operated (SO), or
      with aortic coarctation for 7 (AC7) and 14 days (AC14) were used for agonist
      induced pressor responses in vehicle (physiological saline)- and antagonist
      treated anesthetized animals, immunoblot analysis (alpha(1A)- and alpha(1D)
      adrenoceptor in aorta and caudal arteries), and immunoassay (plasma ATII). The
      alpha(1D)-adrenoceptor antagonist, BMY-7378 (BMY) blocked noradrenaline-induced
      responses in the order SO > AC7 ? AC14; in contrast, the alpha(1A)-adrenoceptor
      antagonist RS-100329 (RS), produced a marginal shift to the right of the dose
      response curve to noradrenaline, along with a strong decrease of the maximum
      pressor effect in the order SO > AC7 = AC14. The potency of the alpha(1A)
      adrenoceptor agonist A-61603 increased in rats with AC14, and responses were
      inhibited by RS in the order AC14 > AC7 > SO. In aorta, alpha(1D)-adrenoceptor
      protein increased in AC7 and decreased in AC14; alpha(1A)-adrenoreceptor protein
      increased in the caudal artery of AC7 and returned to control values in AC14.
      Plasma ATII increased in AC7 and AC14, compared with SO rats. These results
      suggest an early and direct relationship between ATII and alpha(1D)
      adrenoreceptors in the development of hypertension in this experimental model.

PMID- 22149310
TI  - An initial factor analysis of prominent aspects of health experiences for women
      with neck-shoulder pain.
AB  - PURPOSE: The prospect of adequate comparisons is essential to decide on the
      effectiveness of different treatments. As there is a lack of unity in choice of
      questionnaires and included measures concerning musculoskeletal disorders,
      further investigations based on international recommendations are of interest.
      The intention of present study was to initiate the development of a clinically
      useful short-form questionnaire. The aim was to select items that capture
      prominent health aspects for women with neck-shoulder pain and thereby reduce the
      number of items to a clinically more convenient amount, and to determine the
      underlying structure of included items. METHOD: Data were collected in a
      randomised controlled trial including women with non-specific neck-shoulder pain
      >3 months (n = 117). Data collection included three core domains: pain intensity,
      physical and emotional functioning, and analysis was performed using Principal
      component analysis, and Varimax rotation. RESULTS: The resulting 9-factor
      solution included interference, solicitous/distracting responses, mood and
      feelings about self and relations, pain intensity, punishing responses, personal
      growth, life control, sleep, and appetite (29 items). CONCLUSIONS: The results
      will contribute to the development of a reduced battery of questions representing
      core dimensions. Such questionnaire would lighten the assessment load in the
      clinic as well as in research.

PMID- 22149312
TI  - Effect of betaine on the hepatic damage from orotic acid-induced fatty liver
      development in rats.
AB  - Betaine prevents hepatic damage caused by ethanol and carbone tetrachloride
      (CCl4) in rats. Present study was to investigate the effect of betaine on the
      hepatic microsomal triglyceride transfer protein (MTP) mRNA expression in orotic
      acid (OA)-induced fatty liver in rats. OA feeding was attributed to the
      significant increase in the hepatic levels of triglyceride and the serum levels
      of ALT and AST and resulted in typical histology of fatty liver contained
      numerous largely fat droplets. While concomitant supplementation of betaine to OA
      diet was slightly reduced the hepatic triglyceride concentrations and was
      significantly decreased ALT activity. Hepatic MTP mRNA expression by OA treatment
      increased by 14% despite triglyceride accumulation in the liver in OA treatment
      rats relative to rats fed a normal diet without OA supplemented, but MTP
      expression by simultaneous supplementation of OA and betaine was slightly
      decreased by 7.9% as compared to the OA-feeding rats. A significant elevation of
      TBARS contents in the liver homogenate, microsome, and mitochondrial fractions of
      the OA-feeding rats compared with the normal rats, however, these increases were
      significantly or slightly decreased by simultaneous addition of OA and betaine.
      The increases of hepatic OA and betaine levels in OA feeding rats was also found
      when compared to the normal rats, but these increases were significantly lowered
      in the concomitant supplementation OA and betaine. The content of Fe was
      significantly increased in the OA feeding rats, but this elevation showed
      significantly recovered as low as the normal level by concomitant with OA and
      betaine. Zinc content was also significantly decreased in the OA feeding rats
      compared with the normal rats, but this reduction was more significantly elevated
      by concomitant with OA and betaine. Hepatic glutathione content in the OA feeding
      rats was similar to that of the normal rats, but this content was slightly
      reduced without statistically significant differences. But, a significant
      elevation in the hepatic glutathione content was found in the simultaneously
      administration OA and betaine. The hepatocytes contained numerous largely fat
      droplets induced by OA administration and was slightly reduced by simultaneous
      supplementation of OA and betaine. Present study demonstrated that betaine has a
      weak preventive action on the OA-induced triglyceride accumulation.

PMID- 22149314
TI  - Dronedarone: a new hope for stroke prevention in atrial fibrillation?

PMID- 22149315
TI  - Defining the role of lipoprotein apheresis in the management of familial
      hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal co-dominant disorder
      characterized by a marked elevation of serum low-density lipoprotein (LDL)
      cholesterol (LDL-C) concentration, which in turn is associated with a greatly
      increased risk of premature cardiovascular disease. International consensus
      recommends the use of statins as the first line of treatment for patients with
      this condition. However, homozygote FH patients with persistently elevated LDL-C
      levels are usually resistant to multiple-drug therapy. Fortunately, LDL apheresis
      (or simply 'lipoprotein apheresis') provides a treatment option for patients who
      are refractory or intolerant to lipid-lowering medications, or if there is
      progressive cardiovascular disease despite maximal drug therapy. Lipoprotein
      apheresis is an extracorporeal LDL-C-lowering treatment similar in concept to
      renal dialysis. There are now five main methods for extracorporeal lipoprotein
      apheresis in use, namely dextran sulfate adsorption (DSA), heparin extracorporeal
      LDL precipitation (HELP), polyacrylate full blood adsorption (PFBA or DALI(r)
      system) using hemoperfusion, immunoadsorption, and filtration plasmapheresis.
      Lipoprotein apheresis has been shown to be successful in reducing LDL-C levels,
      as well as levels of lipoprotein(a) [Lp(a)], a prothrombotic proatherogenic
      lipoprotein. In contrast, however, lipoprotein apheresis seems to have a smaller
      effect in preventing atherosclerosis progression, thus suggesting that a major
      component of the reduction in cardiovascular events may be mediated by mitigating
      Lp(a) levels. Side effects are infrequent and mild, and have mainly consisted of
      lightheadedness, nausea, vomiting, and hypotension. As these are often bradykinin
      mediated and associated with concomitant ACE inhibitor use, angiotensin type 2
      receptor antagonists should be used instead of ACE inhibitors with DALI and PFBA.
      Nevertheless, there is scope for wider application of lipoprotein apheresis. The
      high cost and invasive nature of lipoprotein apheresis limits uptake; however, it
      is an important treatment modality that should be considered in carefully
      selected patients. National and international registries compiling outcome data
      for lipoprotein apheresis need to be established to help expand the evidence base
      regarding its effectiveness.

PMID- 22149316
TI  - Apolipoprotein E mimetics and cholesterol-lowering properties.
AB  - Apolipoprotein E (apoE) is a ligand for clearance of lipoprotein remnants such as
      chylomicrons and very low-density lipoproteins. It has anti-atherogenic and anti
      inflammatory properties. Therefore, there is extensive ongoing research to create
      peptides that can mimic properties of apoE. A number of synthetic peptides that
      encompass different regions of apoE have been studied for inhibiting inflammatory
      states, including Alzheimer disease. However, peptides that clear atherogenic
      lipoproteins, analogous to apoE, via enhanced hepatic uptake have not been
      previously reviewed. Toward this end, we describe the design and studies of a
      dual-domain apoE mimetic peptide, Ac-hE18A-NH(2). This peptide consists of
      residues 141-150, the putative receptor-binding region of human apoE, covalently
      linked to a well characterized class A amphipathic helix, 18A, which has no
      sequence homology to any other exchangeable apolipoprotein sequences. It
      demonstrates dramatic effects in reducing plasma cholesterol levels in
      dyslipidemic mouse and rabbit models. We discuss the scientific rationale and
      review the literature for the design and efficacy of the peptide. Analogous to
      apoE, this peptide bypasses the low-density lipoprotein receptor for the hepatic
      uptake of atherogenic lipoproteins via heparan sulfate proteoglycan (HSPG). ApoE
      mimetics such as Ac-hE18A-NH(2) may therefore restore or replace ligands in
      genetically induced hyperlipidemias to enable reduction in atherogenic
      lipoproteins via HSPG even in the absence of functional low-density lipoprotein
      receptors. Therefore, this and similar peptides may be useful in the treatment of
      dyslipidemic disorders such as familial hyperlipidemia and atherosclerosis.

PMID- 22149317
TI  - Cardiovascular disease and therapeutic drug-related cardiovascular consequences
      in HIV-infected patients.
AB  - The incidence of cardiovascular disease is greatly increased in the HIV-infected
      population compared with people of the same age without HIV. Cardiovascular
      manifestations of HIV/AIDS include, but are not limited to, accelerated
      atherosclerosis, pulmonary arterial hypertension, vasculitis, myocarditis,
      cardiomyopathy, pericardial diseases, malignancy (myocardial Kaposi sarcoma and B
      cell immunoblastic lymphoma), and endocarditis. Drug effects and interactions
      that challenge the cardiovascular system are even more prevalent in this
      population, and careful review and surveillance of medication effects is crucial
      as is careful selection of highly active antiretroviral therapy. A focused
      assessment and understanding of disease prevalence and presentation is needed as
      symptoms may be non-specific and cardiovascular physical examination findings
      indeterminate due to co-morbid conditions in the patient population now living
      with chronic HIV infection.

PMID- 22149318
TI  - Dronedarone and the incidence of stroke in patients with paroxysmal or persistent
      atrial fibrillation: a systematic review and meta-analysis of randomized trials.
AB  - BACKGROUND: Stroke is the most feared complication of atrial fibrillation (AF).
      Dronedarone is an antiarrhythmic drug with multichannel-blocking properties.
      Recently, a post hoc analysis of a large randomized trial has suggested a
      reduction of stroke risk in patients with paroxysmal or persistent AF receiving
      dronedarone. OBJECTIVE: We performed a systematic review and meta-analysis on the
      effect of dronedarone on the occurrence of stroke or transient ischemic attack
      (TIA) in patients with paroxysmal or persistent AF. METHODS: We searched PubMed,
      EMBASE, and ISI Web of Knowledge as well as abstracts of major conferences for
      randomized trials comparing dronedarone with placebo in patients with paroxysmal
      or persistent AF. The endpoint was the occurrence of stroke or TIA during follow
      up. Fixed effect risk differences (RDs) were calculated with the Mantel-Haenszel
      method. We also performed random effects analysis with the DerSimonian Laird
      method. RESULTS: Four trials were included in the analysis; a total of 5967
      patients were analyzed, 3183 receiving dronedarone 400 mg twice daily and 2784
      receiving placebo. 160 strokes or TIAs were reported in the four trials: 67 in
      the dronedarone group (2.1%) and 93 in the placebo group (3.3%). In the fixed
      effect model, patients in the dronedarone group had a significantly lower risk
      for the occurrence of stroke or TIA during follow-up compared with patients in
      the placebo group. The RD of the incidence of stroke or TIA in all trials between
      patients randomized to dronedarone and those randomized to placebo was -0.0094
      (95% confidence interval [CI] -0.0178, -0.0011; p = 0.027). The ATHENA trial had
      by far the highest statistical weight (79.5%). There was no evidence of
      heterogeneity (chi2 = 2.41, p = 0.300). In the random effects model, the
      statistical weight of the ATHENA trial was much lower (45.1%) and the RD for
      stroke or TIA between the dronedarone and the placebo groups did not reach
      statistical significance (RD -0.0064, 95% CI -0.0144, 0.0016; p = 0.120).
      LIMITATIONS: First, stroke was not a prespecified outcome measure in the included
      trials. Second, we did not analyze trials studying patients with permanent AF;
      very recent data show an adverse outcome in patients with permanent AF receiving
      dronedarone. CONCLUSIONS: The meta-analysis indicates a reduced risk of stroke or
      TIA in patients with paroxysmal or persistent AF receiving dronedarone. These
      findings are largely due to the results of the ATHENA trial. Further research on
      this topic is necessary.

PMID- 22149320
TI  - HMG-CoA reductase inhibitor (Statin) therapy and coronary atherosclerosis in
      Japanese subjects: role of high-density lipoprotein cholesterol.
AB  - BACKGROUND: The level of serum low-density lipoprotein cholesterol (LDL-C)
      achieved and change in serum LDL-C level in response to HMG-CoA reductase
      inhibitor (statin) therapy may not be reflected in coronary plaque regression in
      Japanese subjects, and plaque regression has occurred in many cases in the
      absence of any marked decrease in serum LDL-C level. We hypothesized that the
      indicators of coronary plaque regression in response to statin therapy in a
      Japanese population are different from the indicators in Western populations.
      OBJECTIVE: The purpose of this study was to investigate the predictors of
      coronary plaque regression in Japanese patients with coronary artery disease
      (CAD) using a receiver-operating-characteristic (ROC) analysis. METHODS: A 6
      month prospective observational study to identify predictors of regression of
      coronary plaque as assessed by volumetric intravascular ultrasound was conducted
      on 113 CAD patients receiving usual doses of pravastatin at Nihon University
      Surugadai Hospital, Tokyo, Japan. RESULTS: The mean pravastatin dose was 12.5 +/-
      3.2 mg/day. After 6 months of therapy, the average change in plaque volume was 
      9.9% (p < 0.0001 vs baseline). Body mass index (BMI) before pravastatin therapy
      was significantly lower in the plaque regression group than in the plaque
      progression group (23.5 +/- 2.8 kg/m2 vs 25.3 +/- 2.5 kg/m2, p < 0.01).
      Furthermore, significant increases in serum levels of high-density lipoprotein
      cholesterol (HDL-C) and apolipoprotein (apo) A-1, and decreases in LDL-C/HDL-C,
      apoB/apoA-1, and monocyte count were observed in the plaque regression group (n =
      90) in comparison with the plaque progression group (n = 23), while there were no
      differences in achieved LDL-C levels between the groups (101 +/- 25 mg/dL vs 101
      +/- 24 mg/dL). The changes in plaque volume correlated with the changes in serum
      levels of HDL-C (r = -0.496, p < 0.0001), LDL-C/HDL-C (r = 0.361, p < 0.0001),
      apoA-1 (r = -0.362, p = 0.0005), apoB/apoA-1 (r = 0.314, p = 0.0003), monocyte
      count (r = 0.325, p = 0.0004), and with baseline BMI (r = 0.278, p = 0.003), but
      not with the change in LDL-C level (r = 0.023, p = 0.860). Moreover, an ROC
      analysis showed that the change in HDL-C level was better than any other
      parameter in terms of evaluating the predictor of plaque regression because it
      had a larger area under the ROC curve (0.751; sensitivity: 76.9%; specificity:
      60.9%; cut off value: +/-0%). CONCLUSIONS: Even with modest LDL-C lowering to
      maintain the serum LDL-C level at only 100 mg/dL, we demonstrated that reduction
      of the coronary plaque volume can be achieved by elevation of the serum HDL-C.
      The results suggest that the ameliorating action of statins on lipid metabolism
      and sensitivity to their inhibitory effect on the progression of coronary plaque
      may be different in Japanese and Western populations.

PMID- 22149319
TI  - Comparing antihypertensive effect and plasma ciclosporin concentration between
      amlodipine and valsartan regimens in hypertensive renal transplant patients
      receiving ciclosporin therapy.
AB  - BACKGROUND: Hypertension, a major complication in kidney transplant recipients,
      is associated with premature death and graft loss. However, an optimal
      antihypertensive therapy for these patients has not been established [Chinese
      Clinical Trial Registry No. ChiCTR-TRC-10001071]. OBJECTIVE: The aim of the
      present study was to evaluate the effect of amlodipine and valsartan on BP
      control in renal transplant patients and to analyze the correlation between
      cytochrome P450 (CYP) 3A5 or multidrug resistance-1 gene (MDR1) genotype and the
      antihypertensive effect of these two regimens. METHODS: 150 renal transplant
      patients with stage 1 or 2 hypertension were enrolled in the trial. Patients were
      randomly assigned to amlodipine or valsartan. Metoprolol was added if BP was not
      under control after 4 weeks. BP and plasma levels of ciclosporin were monitored
      during the 24-week trial. CYP3A5 and MDR1 genotypes were determined using a
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. RESULTS: The demographic features and baseline BP were similar between
      these two groups. During the 24-week trial, the reduction of systolic BP (SBP)
      was similar between the amlodipine and valsartan groups. However, the reduction
      of diastolic BP (DBP) was significantly greater in the amlodipine group compared
      with the valsartan group at 12, 16, and 24 weeks of treatment. The plasma level
      of ciclosporin at 2 hours of medication was significantly higher in the
      amlodipine group than in the valsartan group after 4 weeks of the trial. The
      reduction of DBP at 24 weeks was greater in the subjects with CYP3A5 *3/*3
      variant than in those with CYP3A5*1/*1 variant (-13.5 +/- 1.9 mmHg vs -8.7 +/-
      1.6 mmHg, p < 0.05). CONCLUSION: The present study demonstrated that amlodipine
      produced a greater reduction of DBP than valsartan, although both amlodipine and
      valsartan resulted in satisfactory control of BP in patients with renal
      transplantation. Administration of amlodipine significantly increased the plasma
      concentration of ciclosporin, and its effects on BP control and ciclosporin
      concentration may be associated with the CYP3A5 genotype in these subjects
      [Chinese Clinical Trial Registry No. ChiCTR-TRC-10001071].

PMID- 22149321
TI  - Prognostic utility of serum potassium in chronic digoxin toxicity: a case-control
      study.

PMID- 22149322
TI  - The impact of education on sexual behavior in sub-Saharan Africa: a review of the
      evidence.
AB  - Many studies have attempted to determine the relationship between education and
      HIV status. However, a complete and causal understanding of this relationship
      requires analysis of its mediating pathways, focusing on sexual behaviors. We
      developed a series of hypotheses based on the differential effect of educational
      attainment on three sexual behaviors. We tested our predictions in a systematic
      literature review including 65 articles reporting associations between three
      specific sexual behaviors -- sexual initiation, number of partners, and condom
      use -- and educational attainment or school enrollment in sub-Saharan Africa. The
      patterns of associations varied by behavior. The findings for condom use were
      particularly convergent; none of the 44 studies using educational attainment as a
      predictor reviewed found that more educated people were significantly less likely
      to use condoms. Findings for sexual initiation and number of partners were more
      complex. The contrast between findings for condom use on the one hand and sexual
      initiation and number of partners on the other supports predictions based on our
      theoretical framework.

PMID- 22149323
TI  - Caffeine Expectancy Questionnaire (CaffEQ): construction, psychometric
      properties, and associations with caffeine use, caffeine dependence, and other
      related variables.
AB  - Expectancies for drug effects predict drug initiation, use, cessation, and
      relapse, and may play a causal role in drug effects (i.e., placebo effects).
      Surprisingly little is known about expectancies for caffeine even though it is
      the most widely used psychoactive drug in the world. In a series of independent
      studies, the nature and scope of caffeine expectancies among caffeine consumers
      and nonconsumers were assessed, and a comprehensive and psychometrically sound
      Caffeine Expectancy Questionnaire (CaffEQ) was developed. After 2 preliminary
      studies, the CaffEQ was administered to 1,046 individuals from the general
      population along with other measures of interest (e.g., caffeine use history,
      anxiety). Exploratory factor analysis of the CaffEQ yielded a 7-factor solution.
      Subsequently, an independent sample of 665 individuals completed the CaffEQ and
      other measures, and a subset (n = 440) completed the CaffEQ again approximately 2
      weeks later. Confirmatory factor analysis revealed good model fit, and test
      retest reliability was very good. The frequency and quantity of caffeine use were
      associated with greater expectancies for withdrawal/dependence, energy/work
      enhancement, appetite suppression, social/mood enhancement, and physical
      performance enhancement and lower expectancies for anxiety/negative physical
      effects and sleep disturbance. Caffeine expectancies predicted various caffeine-
      associated features of substance dependence (e.g., use despite harm, withdrawal
      incidence and severity, perceived difficulty stopping use, tolerance).
      Expectancies for caffeine consumed via coffee were stronger than for caffeine
      consumed via soft drinks or tea. The CaffEQ should facilitate the advancement of
      our knowledge of caffeine and drug use in general.

PMID- 22149324
TI  - The MMPI-2 computerized adaptive version (MMPI-2-CA) in a Veterans Administration
      medical outpatient facility.
AB  - The ability to screen quickly and thoroughly for psychological difficulties in
      existing and returning combat veterans who are seeking treatment for physical
      ailments would be of significant benefit. In the current study, item and time
      savings, as well as extratest correlations, associated with an audio-augmented
      version of the computerized adaptive Minnesota Multiphasic Personality Inventory
      2 (MMPI-2-CA) are examined in a group of 273 male veterans, ages 26-87 years.
      Results indicated an average item savings of approximately 103 items (18.6%),
      with a corresponding time savings of approximately 12 min (24.3%), for the MMPI-2
      CA compared with conventional computerized administration of the test, as well as
      comparability in terms of test-retest coefficients and correlations with external
      measures. Future directions of adaptive personality testing are discussed.

PMID- 22149325
TI  - Incremental validity of spouse ratings versus self-reports of personality as
      predictors of marital quality and behavior during marital conflict.
AB  - The personality traits of neuroticism and agreeableness are consistently related
      to marital quality, influencing the individual's own (i.e., actor effect) and the
      spouse's marital quality (i.e., partner effect). However, this research has
      almost exclusively relied on self-reports of personality, despite the fact that
      spouse ratings have been found to have incremental validity over self-reports for
      a variety of other important outcomes. In a study of 300 middle-aged and older
      married couples, we examined the incremental validity of spouse ratings of
      neuroticism and agreeableness in predicting concurrent levels of self-reported
      marital quality, observations of behavior during a marital disagreement task, and
      depressive symptoms. Neuroticism and agreeableness had expected actor and partner
      effects on each of these outcomes. Spouse ratings of these traits demonstrated
      incremental validity in estimates of actor and partner effects on marital
      quality, marital behavior, and depressive symptoms. Results suggest that spouse
      ratings of personality may be important additions to the typical reliance on self
      reports for research and clinical assessment in marriage.

PMID- 22149326
TI  - Convergent validity of and bias in maternal reports of child emotion.
AB  - This study examined the convergent validity of maternal reports of child emotion
      in a sample of 190 children between the ages of 3 and 6. Children completed a
      battery of 10 emotion-eliciting laboratory tasks; their mothers and untrained
      naive observers rated child emotions (happiness, surprise, fear, sadness, and
      anger) following each task, and trained coders rated videotapes of each task for
      the same emotions. Consistent with studies using other designs, maternal reports
      demonstrated weak to moderate convergence with the other rating methods.
      Extending prior research, a number of maternal characteristics (particularly
      lifetime psychiatric diagnoses and personality traits) were associated with their
      reports of child emotions in the lab, above and beyond the effects of objective
      coding and observer reports of child emotions. For some emotions, mothers' mental
      health and dispositional variables were more strongly related to their reports of
      the child's emotions than were objective indices of the child's observable
      emotional behavior.

PMID- 22149327
TI  - An evaluation of the reliability and construct validity of eating disorder
      measures in white and black women.
AB  - Most measures of eating disorder symptoms and risk factors were developed in
      predominantly White female samples. Yet eating disorders affect individuals of
      all racial and ethnic backgrounds. Black women appear more vulnerable to certain
      forms of eating pathology, such as binge eating, and less susceptible to other
      eating disorder symptoms and risk factors, such as body dissatisfaction, compared
      with their White peers. Despite concern that extant measures do not adequately
      assess eating concerns among Black women, the construct validity of scores on
      most of these measures has not been adequately examined within this population.
      This study included 2,208 Black and White women who completed the following: the
      Binge Eating Scale (BES), the Eating Disorder Diagnostic Scale (EDDS), the Eating
      Attitudes Test-26 (EAT-26), the Eating Disorder Inventory Body Dissatisfaction
      and Drive for Thinness subscales, the Bulimia Test-Revised (BULIT-R), the
      Multidimensional Body-Self Relations Questionnaire-Appearance Evaluation subscale
      (MBSRQ-AE), and the Objectified Body Consciousness Scale (OBCS). Most measures
      yielded internally consistent scores in both races. Confirmatory factor analyses
      indicated that loadings for some measures, including the EAT-26 and EDDS, were
      not invariant across groups and thus do not assess equivalent constructs in White
      and Black women. However, others, including the BULIT-R, BES, OBCS, and MBSRQ-AE,
      exhibited factorial invariance in both races. Results suggest scores are likely
      not equivalent across races for several popular measures of eating disorder
      symptoms and risk factors. Thus, it is recommended that researchers and
      clinicians obtain additional information regarding racial/cultural factors when
      using these instruments with Black women.

PMID- 22149328
TI  - The factor structure of the Autobiographical Memory Test in recent trauma
      survivors.
AB  - The objective of this study was to examine the psychometric properties of the
      Autobiographical Memory Test (AMT), which is widely used to measure overgeneral
      autobiographical memory in individuals with depression and a trauma history. Its
      factor structure and internal consistency have not been explored in a clinical
      sample. This study examined the psychometric properties of the AMT in a sample of
      recent trauma survivors (N = 194), who completed the AMT 2 weeks after a trauma.
      Participants were also assessed with structured clinical interviews for current
      acute stress disorder and current and past major depressive disorder.
      Confirmatory factor analysis and item response theory were used to analyze the
      AMT in the whole sample. The factor structure of the AMT was also compared for
      (a) individuals with and without lifetime major depressive disorder and (b)
      individuals with current (posttrauma) major depressive disorder and/or acute
      stress disorder versus those with neither disorder. In all of these analyses, the
      AMT with cues of positive and negative valence had a 1-factor structure, which
      replicates work in nonclinical samples. Based on analyses of the whole sample,
      scores from the AMT had a reliability estimate of .72, and standard error of
      measurement was lowest for people who scored low on memory specificity. In
      conclusion, the AMT measures 1 factor of memory specificity in a clinical sample
      and can yield reliable scores for memory specificity. More psychometric studies
      of the AMT are needed to replicate these results with similar and other clinical
      populations.

PMID- 22149329
TI  - Electron trapping in InP nanowire FETs with stacking faults.
AB  - Semiconductor III-V nanowires are promising components of future electronic and
      optoelectronic devices, but they typically show a mixed wurtzite-zinc blende
      crystal structure. Here we show, theoretically and experimentally, that the
      crystal structure dominates the conductivity in such InP nanowires. Undoped
      devices show very low conductivities and mobilities. The zincblende segments are
      quantum wells orthogonal to the current path and our calculations indicate that
      an electron concentration of up to 4.6 * 10(18) cm(-3) can be trapped in these.
      The calculations also show that the room temperature conductivity is controlled
      by the longest zincblende segment, and that stochastic variations in this length
      lead to an order of magnitude variation in conductivity. The mobility shows an
      unexpected decrease for low doping levels, as well as an unusual temperature
      dependence that bear resemblance with polycrystalline semiconductors.

PMID- 22149330
TI  - Tocotrienols prevent hydrogen peroxide-induced axon and dendrite degeneration in
      cerebellar granule cells.
AB  - It is well known that reactive oxygen species (ROS) attack several living tissues
      and increase the risk of development and progression of serious diseases. In
      neuronal level, ROS induce cell death in concentration-dependent fashion.
      However, little is known about the mechanisms of neuronal changes by ROS prior to
      induction of cell death. Here we found that treatment of cerebellar granule
      neurons (CGCs) with 0.5 MUM hydrogen peroxide induced axonal injury, but not cell
      death. The number of dendrites remarkably decreased in hydrogen peroxide-treated
      CGCs, and extensive beading was observed on survival dendrites. In addition, an
      abnormal band of the original collapsin response mediator protein (CRMP)-2 was
      detected by Western blotting in hydrogen peroxide-treated CGCs. Treatment with
      each tocotrienol isoform prevented axonal and dendrite degeneration and induction
      of the abnormal band of the original band of CRMP-2 in hydrogen peroxide-treated
      CGCs. These results indicate that treatment with tocotrienols may therefore be
      neuroprotective in the presence of hydrogen peroxide by preventing changes to the
      CRMP-2 that occur before neuron death.

PMID- 22149331
TI  - Nucleic acid-binding polymers as anti-inflammatory agents: reducing the danger of
      nuclear attack.

PMID- 22149332
TI  - Age-associated B cells: are they the key to understanding why autoimmune diseases
      are more prevalent in women?

PMID- 22149333
TI  - In vitro diagnosis of IgE-mediated allergy: breakthroughs in the last decade.

PMID- 22149334
TI  - Asthma: developments in targeted therapy.

PMID- 22149335
TI  - Probiotics and prebiotics in allergy prevention and treatment: future prospects.

PMID- 22149337
TI  - Prospective, double-blind, placebo-controlled trials of ecallantide for acute
      attacks of hereditary angioedema.
AB  - Hereditary angioedema (HAE) is a rare genetic disorder characterized by
      unpredictable, episodic, incapacitating attacks of well-demarcated angioedema in
      the absence of urticaria and pruritus. HAE is due to deficient or dysfunctional
      C1-esterase inhibitor activity, which results in unopposed activation of plasma
      kallikrein, resulting in increased levels of bradykinin. Ecallantide is a potent
      and specific plasma kallikrein inhibitor approved for the treatment of acute
      attacks of HAE affecting any anatomic site. In Phase III clinical trials,
      subcutaneously administered ecallantide demonstrated significant, rapid and
      durable symptom relief. Ecallantide was effective for all attack types, including
      potentially life-threatening laryngeal attacks. The main safety concern is
      potentially serious hypersensitivity reactions, including anaphylaxis.
      Ecallantide represents an important treatment option for the management of acute
      attacks of HAE.

PMID- 22149338
TI  - An overview of the novel H1-antihistamine bilastine in allergic rhinitis and
      urticaria.
AB  - Currently available second-generation H1-antihistamines include a wide group of
      drugs with a better therapeutic index (or risk-benefit ratio) than the classic
      antihistamines, although their properties and safety profiles may differ.
      Bilastine is a newly registered H1-antihistamine for the oral treatment of
      allergic rhinitis and urticaria, with established antihistaminic and antiallergic
      properties. Clinical studies in allergic rhinitis and chronic urticaria show that
      once-daily treatment with bilastine 20 mg is effective in managing symptoms and
      improving patient's quality of life, with at least comparable efficacy to other
      nonsedative H1-antihistamines. As far as studies in healthy volunteers, clinical
      assays and clinical experience can establish, bilastine's safety profile is
      satisfactory, since it lacks anticholinergic effects, does not impair psychomotor
      performance or actual driving, and appears to be entirely free from
      cardiovascular effects.

PMID- 22149339
TI  - Allergy to monoclonal antibodies: cutting-edge desensitization methods for
      cutting-edge therapies.
AB  - Monoclonal antibodies are important therapeutic tools, but their usefulness is
      limited in patients who experience acute infusion reactions, most of which are
      consistent with type I hypersensitivity reactions including anaphylaxis. Patients
      who experience acute infusion reactions face the prospect of stopping treatment
      or switching to an alternative, and potentially more toxic or inferior treatment.
      Another option that overcomes the treatment hurdle of these reactions is rapid
      desensitization, a procedure in which the offending agent is re-administered in a
      step-wise, highly controlled fashion. While the risk of reactions is not
      completely eliminated, desensitization has proven to be a highly effective re
      administration strategy for most patients who otherwise would not be able to
      tolerate their monoclonal antibody therapy owing to drug-induced anaphylaxis.
      This article reviews the current literature on desensitization and other
      readministration protocols to monoclonal antibodies with an emphasis on four
      agents: rituximab, infliximab, cetuximab and trastuzumab.

PMID- 22149340
TI  - HLA associations and Lofgren's syndrome.
AB  - Patients with sarcoidosis can be subgrouped according to organ engagement and
      clinical manifestations. One such subgroup is Lofgren's syndrome (LS),
      constituting a distinct group of sarcoidosis patients with typical clinical
      manifestations, separate genetic associations and an immune response that seems
      to differ from that of non-LS patients. In particular, LS patients have strong
      associations with HLA-DRB1 alleles, and the well-known association with HLA
      DRB1*03 is particularly striking. This particular HLA-DRB1 allele is also a very
      strong marker within that particular group of patients for a prognostically
      favorable disease course. This article will mainly discuss genetic associations
      with LS, and the possible implications of such associations.

PMID- 22149341
TI  - The link between VLA-4 and JC virus reactivation.
AB  - Natalizumab represents an effective biological therapy to treat relapsing
      remitting forms of multiple sclerosis and Crohn's disease by blocking the
      migration of inflammatory cells to the brain and gut. Natalizumab, however, is
      associated with a risk of progressive multifocal leukoencephalopathy (PML) caused
      by the reactivation of JC virus. The emergence of PML in this setting has moved
      PML from being a rare disease mostly seen in HIV-infected individuals to become
      an important cause of complications in patients receiving immunomodulatory
      treatments. The incidence of PML associated with natalizumab treatment is
      approximately 1.5:750, but this increases to approximately 1:100 in patients
      after 24-36 doses based on available estimates of individuals who have a prior
      history of immunosuppressive treatment and are antibody positive to JC virus.
      Natalizumab treatment has raised questions about the pathogenesis of PML but also
      has provided the opportunity to investigate sites of virus latency and mechanisms
      of trafficking to the brain.

PMID- 22149343
TI  - Vaccination to protect against infection of the female reproductive tract.
AB  - Infection of the female genital tract can result in serious morbidities and
      mortalities from reproductive disability, pelvic inflammatory disease and cancer,
      to impacts on the fetus, such as infant blindness. While therapeutic agents are
      available, frequent testing and treatment is required to prevent the occurrence
      of the severe disease sequelae. Hence, sexually transmitted infections remain a
      major public health burden with ongoing social and economic barriers to
      prevention and treatment. Unfortunately, while there are two success stories in
      the development of vaccines to protect against HPV infection of the female
      reproductive tract, many serious infectious agents impacting on the female
      reproductive tract still have no vaccines available. Vaccination to prevent
      infection of the female reproductive tract is an inherently difficult target,
      with many impacting factors, such as appropriate vaccination
      strategies/mechanisms to induce a suitable protective response locally in the
      genital tract, variation in the local immune responses due to the hormonal cycle,
      selection of vaccine antigen(s) that confers effective protection against
      multiple variants of a single pathogen (e.g., the different serovars of Chlamydia
      trachomatis) and timing of the vaccine administration prior to infection
      exposure. Despite these difficulties, there are numerous ongoing efforts to
      develop effective vaccines against these infectious agents and it is likely that
      this important human health field will see further major developments in the next
      5 years.

PMID- 22149342
TI  - Dendritic cells and aging: consequences for autoimmunity.
AB  - The immune system has evolved to mount immune responses against foreign pathogens
      and to remain silent against self-antigens. A balance between immunity and
      tolerance is required as any disturbance may result in chronic inflammation or
      autoimmunity. Dendritic cells (DCs) actively participate in maintaining this
      balance. Under steady-state conditions, DCs remain in an immature state and do
      not mount an immune response against circulating self-antigens in the periphery,
      which maintains a state of tolerance. By contrast, foreign antigens result in DC
      maturation and DC-induced T-cell activation. Inappropriate maturation of DCs due
      to infections or tissue injury may cause alterations in the balance between the
      tolerogenic and immunogenic functions of DCs and instigate the development of
      autoimmune diseases. This article provides an overview of the effects of
      advancing age on DC functions and their implications in autoimmunity.

PMID- 22149344
TI  - Therapy for sarcoidosis: evidence-based recommendations.
AB  - The options for treatment of sarcoidosis have expanded. In this article, we
      outline a stepwise approach to treatment. Recommendations for treatment are based
      on available evidence. While corticosteroids remain the treatment of choice for
      initial systemic therapy, other agents have been shown to be steroid sparing, and
      therefore useful for long-term management. In addition, new agents have proved to
      be useful for patients with refractory disease.

PMID- 22149346
TI  - Playing with dimensions: rational design for heteroepitaxial p-n junctions.
AB  - A design for a heteroepitaxial junction by the way of one-dimensional wurzite on
      a two-dimensional spinel structure in a low-temperature solution process was
      introduced, and it's capability was confirmed by successful fabrication of a
      diode consisting of p-type cobalt oxide (Co(3)O(4)) nanoplate/n-type zinc oxide
      (ZnO) nanorods, showing reasonable electrical performance. During thermal
      decomposition, the 30 degrees  rotated lattice orientation of Co(3)O(4)
      nanoplates from the orientation of beta-Co(OH)(2) nanoplates was directly
      observed using high-resolution transmission electron microscopy. The epitaxial
      relations and the surface stress-induced ZnO nanowire growth on Co(3)O(4) were
      well supported using the first-principles calculations. Over the large area,
      (0001) preferred oriented ZnO nanorods epitaxially grown on the (111) plane of
      Co(3)O(4) nanoplates were experimentally obtained. Using this epitaxial p-n
      junction, a diode was fabricated. The ideality factor, turn-on voltage, and
      rectifying ratio of the diode were measured to be 2.38, 2.5 V and 10(4),
      respectively.

PMID- 22149347
TI  - Ungual and transungual drug delivery.
AB  - Topical therapy is desirable in treatment of nail diseases like onychomycosis
      (fungal infection of nail) and psoriasis. The topical treatment avoids the
      adverse effects associated with systemic therapy, thereby enhancing the patient
      compliance and reducing the treatment cost. However the effectiveness of the
      topical therapies has been limited due to the poor permeability of the nail plate
      to topically applied therapeutic agents. Research over the past one decade has
      been focused on improving the transungual permeability by means of chemical
      treatment, penetration enhancers, mechanical and physical methods. The present
      review is an attempt to discuss the different physical and chemical methods
      employed to increase the permeability of the nail plate. Minimally invasive
      electrically mediated techniques such as iontophoresis have gained success in
      facilitating the transungual delivery of actives. In addition drug transport
      across the nail plate has been improved by filing the dorsal surface of the nail
      plate prior to application of topical formulation. But attempts to improve the
      trans-nail permeation using transdermal chemical enhancers have failed so far.
      Attempts are on to search suitable physical enhancement techniques and chemical
      transungual enhancers in view to maximize the drug delivery across the nail
      plate.

PMID- 22149348
TI  - The effect of perspective and content on brain activation during mentalizing in
      young females.
AB  - In the present functional magnetic resonance imaging (fMRI) study, we
      investigated the role of different brain regions in separate aspects of
      mentalizing. Young females aged 18-19 years were asked to imagine a social
      situation and answer a question. Perspective, self and other, as well as content,
      emotion, and behavior, were varied. Activation was observed in the left
      precuneus, left temporoparietal junction, left medial prefrontal cortex and left
      middle temporal gyrus. Left precuneus and left temporoparietal junction were
      recruited more when taking the perspective of other than when taking the
      perspective of self. Medial prefrontal areas might be more involved during
      mentalizing about emotion versus baseline than about behavior versus baseline.

PMID- 22149349
TI  - Clinical practice guidelines for first-line/after-relapse treatment of patients
      with follicular lymphoma.
AB  - Key points and recommendations   Follicular lymphoma is a subgroup of non-Hodgkin
      lymphomas of B-cell origin, characterized by a pattern of remissions and
      continued relapses. It is the second most common type of lymphoid cancer in
      Western Europe, representing 22-40% of non-Hodgkin lymphomas. The annual
      incidence of the disease has increased in recent decades. At this time, and with
      the arrival of new treatment options, patients' outcomes have significantly
      improved. It is therefore essential to standardize recommendations for the
      treatment and follow-up of patients with follicular lymphoma, in each clinical
      scenario. Searches were performed in Medline (PubMed, 1966-present) and The
      Cochrane Library, using MeSH (Medical Subject Headings) terms whenever possible.
      The best scientific evidence was obtained from selected randomized studies and
      meta-analyses. For recommendations where there was no scientific evidence, the
      consensus of clinical experts was obtained regarding clinical and therapeutic
      attitudes to improve the treatment of these patients. Recommendations are
      compiled according to: (i) induction treatment in first-line; (ii) post-induction
      treatment in first-line; (iii) rescue treatment after relapse; (iv) post
      induction treatment in relapse and (v) subsequent treatments. There are different
      recommendations for each group. They take into account different variables, such
      as therapeutic options, patient follow-up, laboratory and imaging data, previous
      response and special groups. The recommendations contained in this guide have
      been assigned different grades (A, B, C and D), depending on the level of
      evidence on which they are based (where there is no scientific evidence, they
      follow the consensus of Good Clinical Practice: see the Appendix). These
      guidelines provide healthcare professionals with updated and consensual tools for
      the better management of patients with follicular lymphoma.

PMID- 22149350
TI  - First principles analysis of H2O adsorption on the (110) surfaces of SnO2, TiO2
      and their solid solutions.
AB  - Both associative and dissociative H(2)O adsorption on SnO(2)(110), TiO(2)(110),
      and Ti-enriched Sn(1-x)Ti(x)O(2)(110) surfaces have been investigated at low
      ((1)/(12) monolayer (ML)) and high coverage (1 ML) by density functional theory
      calculations using the Gaussian and plane waves formalism. The use of a large
      supercell allowed the simulation at low symmetry levels. On SnO(2)(110),
      dissociative adsorption was favored at all coverages and was accompanied by
      stable associative H(2)O configurations. Increasing the coverage from (1)/(12) to
      1 ML stabilized the (associatively or dissociatively) adsorbed H(2)O on
      SnO(2)(110) because of the formation of intermolecular H bonds. In contrast, on
      TiO(2)(110), the adsorption of isolated H(2)O groups ((1)/(12) ML) was more
      stable than at high coverage, and the favored adsorption changed from
      dissociative to associative with increasing coverage. For dissociative H(2)O
      adsorption on Ti-enriched Sn(1-x)Ti(x)O(2)(110) surfaces with Ti atoms preferably
      located on 6-fold-coordinated surface sites, the analysis of the Wannier centers
      showed a polarization of electrons surrounding bridging O atoms that were bound
      simultaneously to 6-fold-coordinated Sn and Ti surface atoms. This polarization
      suggested the formation of an additional bond between the 6-fold-coordinated
      Ti(6c) and bridging O atoms that had to be broken upon H(2)O adsorption. As a
      result, the H(2)O adsorption energy initially decreased, with increasing surface
      Ti content reaching a minimum at 25% Ti for (1)/(12) ML. This behavior was even
      more accentuated at high H(2)O coverage (1 ML) with the adsorption energy
      decreasing rapidly from 145.2 to 101.6 kJ/mol with the surface Ti content
      increasing from 0 to 33%. A global minimum of binding energies at both low and
      high coverage was found between 25 and 33% surface Ti content, which may explain
      the minimal cross-sensitivity to humidity previously reported for Sn(1
      x)Ti(x)O(2) gas sensors. Above 12.5% surface Ti content, the binding energy
      decreased with increasing coverage, suggesting that the partial desorption of
      H(2)O is facilitated at a high fractional coverage.

PMID- 22149351
TI  - IkappaB kinase alpha and cancer.
AB  - IkappaB kinase alpha (Ikk-alpha) gene mutations and IKK-alpha downregulation have
      been detected in various human squamous cell carcinomas (SCCs), which are
      malignancies derived from squamous epithelial cells. These squamous epithelial
      cells distribute to many organs in the body; however, the epidermis is the only
      organ mainly composed of stratified squamous epithelial cells, called
      keratinocytes. SCC is the second most common type of skin cancer. Reducing IKK
      alpha expression promotes tumor initiation, and its loss greatly enhances tumor
      progression from benign papillomas to malignant carcinomas during chemical skin
      carcinogenesis in mice. Thus, IKK-alpha has emerged as a tumor suppressor for
      SCCs. Furthermore, inducible deletion of IKK-alpha in the keratinocytes of adult
      mice causes spontaneous skin papillomas and carcinomas, indicating that IKK-alpha
      deletion functions as a tumor initiator as well as a tumor promoter. This article
      discusses IKK-alpha biological activities and associated molecular events in skin
      tumor development, which may provide insight into the diagnosis, treatment, and
      prevention of human squamous cell carcinomas (SCCs) in the future.

PMID- 22149352
TI  - Extraordinary nonlinear absorption in 3D bowtie nanoantennas.
AB  - This paper reports that arrays of three-dimensional (3D), bowtie-shaped Au
      nanoparticle dimers can exhibit extremely high nonlinear absorption. Near-field
      interactions across the gap of the 3D bowties at the localized surface plasmon
      resonance wavelengths resulted in an increase of more than 4 orders of magnitude
      in local field intensity. The imaginary part of the third-order nonlinear
      susceptibility (Im chi((3))) for the 3D bowtie arrays embedded in a dielectric
      material was measured to be 10(-4) esu, more than 2 orders of magnitude higher
      than reported for other metal nanoparticle-dielectric composites. Moreover, 3D
      dimers with increased nanoscale structure (such as folding) exhibited increased
      optical nonlinearity. These 3D nanoantennas can be used as critical elements for
      nanoscale nonlinear optical devices.

PMID- 22149353
TI  - Arsenic trioxide increases the sensitivity of 786-0 renal carcinoma cells to
      radiotherapy.
AB  - We evaluated the combined effect of As(2)O(3) and ionizing radiation on cultured
      renal carcinoma cells. The cells receiving both As(2)O(3) and radiotherapy had
      more DNA damage, more apoptosis, more reactive oxygen species produced, more
      cells in G(2)/M phase, and a lower mitochondrial membrane potential than cells
      treated with As(2)O(3) only or with radiotherapy only (for all comparisons, p <
      .05). Renal carcinoma cells can be sensitized to ionizing radiation with
      As(2)O(3), and combining As(2)O(3) and radiation had larger effects than
      As(2)O(3) only or radiation only.

PMID- 22149354
TI  - Computer-based assistive technology and changes in daily living after stroke.
AB  - The aim of this study was to examine in depth how computer-based assistive
      technology (AT) for cognitive support influenced the everyday lives of both
      persons who had had a stroke and their significant others. METHOD: Four
      participants, who had experienced cognitive limitations after a stroke, and their
      significant others were included in the study. The study included an intervention
      with a specific type of computer-based AT that was installed in the homes of the
      four participants for a 6-month period. Semistructured interviews were conducted
      before the installation to learn about the participants needs and repeated
      interviews took place after the installation. All collected data were analyzed
      based on qualitative methodology. RESULTS: The findings illustrated how routines
      developed with support from the AT influenced the participants towards increased
      control of their everyday life, and also created daily structure and helped them
      regain social contacts. The findings demonstrated how the spouses also benefitted
      and could reduce their reminding and checking responsibilities. CONCLUSION:
      Computer-based AT has the potential to bring about changes in the everyday life
      for people with cognitive limitations by supporting the development of routines
      and by introducing, maintaining, reinforcing or regaining valuable activities.

PMID- 22149355
TI  - Automatic individual calibration in fall detection--an integrative ambulatory
      measurement framework.
AB  - The objective of the current study was to demonstrate the utility of a new
      integrative ambulatory measurement (IAM) framework by developing and evaluating
      an individual calibration function in fall detection application. Ten healthy
      elderly persons were involved in a laboratory study and tested in a protocol
      comprising various types of activities of daily living and slip-induced backward
      falls. Inertial measurement units attached to the trunk and thigh segments were
      used to measure trunk angular kinematics and thigh accelerations. The effect of
      individual calibration was evaluated with previously developed fall detection
      algorithm. The results indicated that with individual calibration, the fall
      detection performance achieved approximately the same level of sensitivity (100%
      vs. 100%) and specificity (95.25% vs. 95.65%); however, response time was
      significantly lower than without (249 ms vs. 255 ms). It was concluded that the
      automatic individual calibration using the IAM framework improves the performance
      of fall detection, which has a greater implication in preventing/minimising
      injuries associated with fall accidents.

PMID- 22149359
TI  - Trends in hepatic injury associated with unintentional overdose of paracetamol
      (Acetaminophen) in products with and without opioid: an analysis using the
      National Poison Data System of the American Association of Poison Control
      Centers, 2000-7.
AB  - BACKGROUND: Unintended hepatic injury associated with the use of paracetamol
      (acetaminophen)-containing products has been growing. OBJECTIVE: The aim of the
      study was to seek a better understanding of the causes of this observation in
      order to evaluate the potential impact of proposed preventive measures. STUDY
      DESIGN: Retrospective analysis of a large database containing prospectively
      collected patient exposure data, clinical symptomatology and outcome. SETTING:
      The National Poison Data System database for 2000-7 involving exposures to
      paracetamol and an opioid was obtained and analysed. This dataset was limited to
      non-suicidal cases in patients 13 years of age and older. For comparison, the
      parallel, mutually exclusive dataset involving exposures to one or more non
      opioid containing paracetamol products was analysed. OUTCOME MEASURE: Trends in
      the numbers of patients exposed, treated, and mildly and severely injured were
      obtained and compared with each other and with trends calculated from publicly
      available data on sales and population. The association of injury with the number
      of paracetamol-containing products and the reason for taking them were also
      assessed. RESULTS: Comparators: During the study period, the US population of
      those 15 years of age and over rose 8.5%; all pharmaceutical-related calls to all
      US poison centres rose 25%. For the 8-year period from 2001 to 2008, sales of
      over-the-counter paracetamol products rose 5% (single-ingredient products fell
      3%; paracetamol-containing combination cough and cold products rose 11%) and
      prescription paracetamol combination products rose 67%. Opioids with paracetamol:
      A total of 119 731 cases were identified, increasing 70% over the period. The
      exposure merited acetylcysteine treatment in 8995 cases (252% increase). In
      total, 2729 patients (2.3%) experienced some hepatic injury (500% increase).
      Minor injuries rose faster than severe injuries (833% vs 280%) and most injuries
      (73.0%) were from overuse of a single combination product only, but the injury
      rate increased with use of more than one paracetamol-containing product. Abuse
      and misuse accounted for 34% of cases but 58% of the severe injuries. Paracetamol
      without opioid: A total of 126 830 cases were identified, increasing 44%, and 15
      706 cases merited acetylcysteine (70% increase). A total of 4674 patients (3.7%)
      experienced some hepatic injury (134% increase). [corrected] Use of more than one
      non-opioid paracetamol product occurred in 7.3% of patients and was associated
      with a lower injury rate. CONCLUSIONS: Hepatic injury associated with paracetamol
      use is increasing significantly faster than population, paracetamol product sales
      and poison centre use. This suggests a growing portion of consumers is self
      dosing paracetamol beyond the toxic threshold. This is true for paracetamol with
      and without opioids, but the increase in hepatic injury is greater when
      paracetamol is taken with an opioid. This disproportionate rise is greatest with
      misuse and abuse of paracetamol products in combination with opioids. Increasing
      self-dosage of the opioid combination products for the opioid effect is likely to
      result in more cases of toxic exposure to paracetamol. In contrast, cases of
      exposure to paracetamol-containing cough and cold products are underrepresented
      among those injured. In the absence of opioid-containing products, consumption of
      more than one paracetamol-containing product did not contribute to injury.
      Efforts to modulate unintentional paracetamol-related hepatic injury should
      consider these associations.

PMID- 22149360
TI  - Biomedical applications and chemical nature of three dyes first synthesized by
      Raphael Meldola: isamine blue, Meldola's blue and naphthol green B.
AB  - Brief accounts are given of the chemical nature, and past and current biomedical
      applications of three dyes first synthesized by Raphael Meldola: isamine blue,
      Meldola's blue and naphthol green B.

PMID- 22149361
TI  - Morphologic diversity of the minor salivary glands of the rat: fertile ground for
      studies in gene function and proteomics.
AB  - In this article the locations and histologic and ultrastructural features of all
      of the minor salivary glands of the rat are presented; similarities and
      differences among them are highlighted. These glands are almost as diverse
      morphologically as the major salivary glands of the rat. The acini of von Ebner's
      glands are serous; those of the anterior and posterior buccal glands and minor
      sublingual glands are mucous; and those of the glossopalatal, palatal, and
      Weber's glands are mucous with serous demilunes. The anterior buccal, minor
      sublingual and von Ebner's glands have striated and stratified columnar ducts,
      while only the minor sublingual and von Ebner's glands have intercalated ducts.
      The glossopalatal, palatal, posterior buccal and Weber's glands have none of
      these ducts; the tubulo-acini drain abruptly into short terminal ducts composed
      of stratified squamous epithelium. All of the mucous acini react with an antibody
      to a mucin (Muc19) of the rat major sublingual gland, but in some of the glands
      the reaction varies in intensity among the acinar cells. Ultrastructurally, the
      mucous secretory granules of the anterior buccal, glossopalatal, palatal and
      Weber's glands are biphasic, while those of the minor sublingual and posterior
      buccal glands are monophasic. Although there is a considerable body of literature
      concerning the development, innervation, physiology and proteomics of von Ebner's
      glands, investigation of the other minor salivary glands of the rat ranges from
      modest to nearly nonexistent.

PMID- 22149362
TI  - Posttraumatic stress disorder and its comorbidity with depression and
      somatisation in the elderly - a German community-based study.
AB  - OBJECTIVES: Even 60 years after World War II, the German elderly population is
      significantly more often affected by posttraumatic symptomatology compared to the
      younger cohorts. This study is addressing prevalence rates of posttraumatic
      symptomatology and its comorbidity with depression and somatisation. METHODS:
      This study examines posttraumatic stress disorder (PTSD) according to DSM-IV,
      partial PTSD, depression and somatisation in a randomly selected sample of the
      German general population aged 60-85 years (N = 1.659) using self-rating
      instruments (Patient Health Questionnaire, PHQ; Post Traumatic Diagnostic Scale,
      PTDS). RESULTS: One-month prevalence rate was 4.0% for DSM-IV PTSD; another 12.2%
      fulfilled the criteria of partial PTSD. A significant increase across the age
      groups was found for partial PTSD. 11.5% of the persons affected by posttraumatic
      symptomatology fulfil the criteria of a somatoform syndrome, 8.6% fulfil the
      criteria of major depression and 10.4% fulfil the criteria of other depressive
      syndromes according to the PHQ. A current posttraumatic symptomatology is
      associated with increased prevalence rates of somatoform and depressive
      disorders. Moreover, traumatic experiences without a current PTSD are associated
      with increased rates of somatoform disorders. CONCLUSION: Posttraumatic
      symptomatology is a common phenomenon in the German elderly population.
      Especially, subsyndromal disorders are very common and increasing across the age
      groups. Posttraumatic symptomatology is associated with an increased risk of
      depressive and somatoform disorders. As posttraumatic symptoms are often
      neglected in geriatric health care, future effort should address the recognition
      and treatment of posttraumatic symptoms in elderly patients.

PMID- 22149363
TI  - Stabilization of protein-loaded starch microgel by polyelectrolytes.
AB  - The interaction of biocompatible polyelectrolytes (chargeable poly(amino acids))
      with oxidized starch microgel particles has been studied. The aim was to form a
      polyelectrolyte complex layer around the outer shell of microgel particles filled
      with functional ingredients to slow down the release of the ingredients from the
      gel and make this process less sensitive to salt. First, the distribution of
      positively charged poly(l-lysine) (PLL) of two different molecular weights
      ("small", 15-30 kDa, and "large", 30-70 kDa) in the negatively charged gel
      particles was measured. The small PLL distributes homogeneously throughout the
      gel particles, but the large PLL forms a shell; i.e., its concentration at the
      outer layer of the particles was found to be much higher than in their core. This
      shell formation does not occur at a relatively high salt concentration (0.07 M).
      The large PLL was selected for further study. It was found that upon addition of
      PLL to lysozyme-loaded gel particles the protein is exchanged by PLL. The
      exchange rate increases with increasing pH, in line with the increasing
      electrostatic attraction between the gel and the polyelectrolyte. Therefore, it
      was decided to use also a negatively charged poly(amino acid), poly(L-glutamic
      acid) (PGA), to form together with PLL a stable polyelectrolyte complex shell
      around the gel particles. This approach turned out to be successful, and the
      PLL/PGA complex layer effectively slows down the release of lysozyme from the
      microgel particles at 0.05 M salt. In addition, it was found that the PLL/PGA
      layer protects the gel particle from degradation by alpha-amylase.

PMID- 22149364
TI  - Atypical AA amyloid deposits in bovine AA amyloidosis.
AB  - In bovine amyloid protein A (AA) amyloidosis, amyloid deposits are typically
      observed in the kidney and spleen at necropsy. To determine the distribution of
      amyloid deposits in cows affected with AA amyloidosis, we examined organs known
      to be sites of amyloid deposits that are also processed for human consumption in
      14 cows: 11 with typical clinical symptoms (typical amyloidosis) and three with
      no typical clinical symptoms (atypical amyloidosis). We found unusually high
      amounts of amyloid deposits in the tongue and other organs in all 14 cows
      regardless of the presence or absence of clinical amyloidosis symptoms. Cows with
      typical amyloidosis had heavier amyloid deposits in the spleen and renal
      glomeruli than cows with atypical amyloidosis. From clinical symptoms and
      histological examinations, we found that cows with typical and atypical
      amyloidosis can be classified into two groups, class I and class II, according to
      the presence or absence of heavy amyloid deposits in the spleen and renal
      glomeruli. However, no significant differences were observed between the amyloid
      fibrils of class I and class II amyloidosis by electron microscopy and Western
      blot analysis.

PMID- 22149365
TI  - Metformin and heart failure: never say never again.
AB  - Metformin represents the cornerstone of treatment for type 2 diabetes mellitus.
      Traditionally, heart failure (HF) was considered a contraindication to its use.
      However, more recent evidence has shown that this should no longer be the case.
      Indeed, studies have demonstrated that metformin may even reduce the risk of
      incident HF and mortality in diabetic patients, while improving up to 2-year
      survival rates in those with HF. In addition, it appears to exert
      cardioprotective actions. Although longer follow-up data and more explicit
      information about the situation in patients with very advanced HF are needed, the
      cardiac safety of metformin has profound clinical implications and may be
      anticipated to further encourage its widespread use.

PMID- 22149366
TI  - Antiplatelet therapy in acute coronary syndromes.
AB  - INTRODUCTION: Antiplatelet therapy is the cornerstone of treatment for patients
      with acute coronary syndromes in the acute phase and in long-term management.
      Over the last few years, new antiplatelet drugs have been developed and the
      therapeutic landscape has rapidly evolved. AREAS COVERED: We review the available
      evidence and most recent data concerning all of the principal classes of
      antiplatelet agents, including aspirin, thienopyridines and glycoprotein IIb/IIIa
      inhibitors, as well the impact of the new drugs prasugrel and ticagrelor and the
      available data concerning cangrelor, elinogrel and PAR-1 inhibitors (still under
      development). EXPERT OPINION: This review considers the management of
      antiplatelet therapy in the light of recent advances, highlighting how to
      identify patients who will receive the greatest benefit from the older and newer
      agents, and underscoring the importance of carefully balancing the risks of
      ischaemia and bleeding in order to improve clinical outcomes. Finally, the paper
      discusses the potential role of functional and genetic tests in guiding the
      choice of antiplatelet therapy in a future perspective of 'personalised
      medicine'.

PMID- 22149367
TI  - Treatment of childhood anxiety disorders: what is the place for antidepressants?
AB  - INTRODUCTION: Anxiety disorders represent one of the most prevalent forms of
      psychopathology among children and adolescents. As these problems tend to persist
      and have a negative impact on young people's development, there is a need for
      evidence-based interventions. Cognitive-behavioral therapy (CBT) is at present
      the treatment of first choice, but pharmacotherapy and in particular
      antidepressant medication may be a viable alternative or adjunct to CBT. AREAS
      COVERED: This paper provides a detailed overview of controlled treatment outcome
      studies on the efficacy of tricyclic antidepressants (TCAs), selective serotonin
      reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors
      (SNRIs) in children and adolescents with anxiety disorders. Further, a discussion
      is provided on how clinically anxious youths should be preferably treated, with
      special focus on the position of pharmacotherapy in the treatment process. EXPERT
      OPINION: The short-term efficacy of antidepressants in anxious youths is good,
      and this is particularly true for SSRIs. Therefore, this type of medication
      should be viewed as a viable treatment option, in particular for youths with
      obsessive-compulsive disorder (OCD) or other severe and pervasive anxiety
      disorders. More research is needed on the long-term effects, the consequences of
      prolonged use of this type of medication for children's developing brains and the
      efficacy of an intervention in which CBT and SSRIs are combined.

PMID- 22149369
TI  - A review of gliptins in 2011.
AB  - INTRODUCTION: Dipeptidylpeptidase-4 (DPP-4) inhibitors offer new options for the
      management of type 2 diabetes (T2DM). AREAS COVERED: This paper is an updated
      review, providing an analysis of both the similarities and the differences
      between the various compounds known as gliptins, currently used in the clinic
      (sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin). This paper
      discusses the pharmacokinetic and pharmacodynamic characteristics of gliptins;
      both the efficacy and safety profiles of gliptins in clinical trials (compared
      with classical glucose-lowering agents), given as monotherapy or in combination,
      including in special populations; the positioning of DPP-4 inhibitors in the
      management of T2DM in recent guidelines; and various unanswered questions and
      perspectives. EXPERT OPINION: The role of DPP-4 inhibitors in the therapeutic
      armamentarium of T2DM is evolving, as their potential strengths and weaknesses
      become better defined. Future critical issues may include the durability of
      glucose control, resulting from better beta-cell protection, positive effects on
      cardiovascular outcomes and long-term safety issues.

PMID- 22149368
TI  - Combination nucleoside/nucleotide reverse transcriptase inhibitors for treatment
      of HIV infection.
AB  - INTRODUCTION: The combination of two nucleoside/nucleotide reverse transcriptase
      inhibitors (N(t)RTIs) and a third agent from another antiretroviral class is
      currently recommended for initial antiretroviral therapy. In general, N(t)RTIs
      remain relevant in subsequent regimens. There are currently six nucleoside
      reverse transcriptase inhibitors and one nucleotide reverse transcriptase
      inhibitor drug entities available, and several formulations that include two or
      more N(t)RTIs in a fixed-dose combination. These entities have heterogeneous
      pharmacological and clinical properties. Accordingly, toxicity, pill burden,
      dosing frequency, potential drug-drug interaction, preexisting antiretroviral
      drug resistance and comorbid conditions should be considered when constructing a
      regimen. This approach is critical in order to optimize virologic efficacy and
      clinical outcomes. AREAS COVERED: This article reviews N(t)RTI combinations used
      in the treatment of HIV-infected adults. The pharmacological properties of each
      N(t)RTI, and the clinical trials that have influenced treatment guidelines are
      discussed. EXPERT OPINION: It is likely that N(t)RTIs will continue to dominate
      the global landscape of HIV treatment and prevention, despite emerging interest
      in N(t)RTI-free combination therapy. Clinical domains where only few alternatives
      to N(t)RTIs exist include treatment of HIV/HBV coinfection and HIV-2. There is a
      need for novel N(t)RTIs with enhanced safety and resistance profiles compared
      with current N(t)RTIs.

PMID- 22149370
TI  - Linagliptin, a dipeptidyl peptidase-4 inhibitor with a unique pharmacological
      profile, and efficacy in a broad range of patients with type 2 diabetes.
AB  - INTRODUCTION: Increasing population age, obesity and physical inactivity mean
      that type 2 diabetes mellitus (T2DM) is increasingly common. Current treatments
      may be limited by adverse events, drug-drug interactions or contraindication/need
      for dose adjustment in patients with renal impairment. AREAS COVERED: This paper
      reviews studies that evaluate the pharmacokinetics, pharmacodynamics and clinical
      efficacy and safety of linagliptin , a dipeptidyl peptidase-4 (DPP-4) inhibitor,
      recently approved in the US, Japan and Europe for the treatment of T2DM. EXPERT
      OPINION: Oral linagliptin, 5 mg once daily, is an effective, well-tolerated DPP-4
      inhibitor, suitable for use in a wide range of patients with T2DM. It is weight
      neutral, without increasing the risk of hypoglycemia, and can be administered
      either alone or in combination with other diabetes treatments. It has a unique
      pharmacological profile within its class and, unlike other DPP-4 inhibitors,
      linagliptin does not require dose adjustment in patients with renal impairment.

PMID- 22149371
TI  - Istradefylline  for the treatment of Parkinson's disease.
AB  - INTRODUCTION: Despite several available therapeutic options to treat the symptoms
      of Parkinson's disease (PD), there are currently no agents that halt or slow the
      progression of disease. Istradefylline is a selective adenosine A(2A) antagonist
      that is currently of interest for the treatment of motor complications in PD.
      AREAS COVERED: This paper reviews the limitations of currently available
      treatment options and discusses the results seen in both animal models and human
      clinical trials that have explored the benefits of istradefylline in PD. EXPERT
      OPINION: The studies outlined continue to suggest that istradefylline may be a
      promising non-dopaminergic therapy for the treatment of PD. It has not been
      proven to be more efficacious than other currently available dopaminergic drugs,
      nor has it been shown to be of significant benefit as monotherapy; however, it
      seems to be a safe and well-tolerated drug that may help with wearing-off
      fluctuations. Istradefylline is not yet an FDA-approved drug. At this time, the
      potential for approval in the US or through the European Medical Agency remains
      unknown.

PMID- 22149372
TI  - Oxaliplatin: a review of approved uses.
AB  - INTRODUCTION: Oxaliplatin, a second-generation platinum analog, has evolved as
      one of the most important therapeutic agents in colorectal cancer (CRC)
      treatment. It has had a major impact on the management and outcome of this
      disease. AREAS COVERED: The pharmacokinetic and pharmacodynamic data of
      oxaliplatin are reviewed in this paper. It also discusses the current clinical
      data regarding the use of oxaliplatin in early colon cancer, locally advanced
      rectal cancer, and in the metastatic setting, with a particular reference to its
      combination with monoclonal antibodies, and strategies for prevention of
      cumulative toxicity. EXPERT OPINION: Oxaliplatin has proven beneficial in the
      treatment of CRC and can currently be regarded as one of the three most important
      chemotherapeutic drugs used in the treatment of both metastatic disease and
      adjuvant therapy in stage II/III after resection. With regards to a median
      overall survival of more than 20 months, and a median progression-free survival
      for first-line treatment of about 9 - 10 months, the majority of patients will
      receive all three compounds (oxaliplatin, fluoropyrimidines and irinotecan)
      during the course of their disease. At the moment there are no drugs in late
      clinical development which might be able to substitute oxaliplatin in its unique
      role in CRC.

PMID- 22149373
TI  - Metformin + saxagliptin for type 2 diabetes.
AB  - INTRODUCTION: Metformin is considered as the first-line drug therapy for the
      management of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors, by
      promoting insulin secretion and reducing glucagon secretion in a glucose
      dependent manner, offer new opportunities for oral therapy after failure of
      metformin. AREAS COVERED: An updated review of the literature demonstrates that
      saxagliptin, a DPP-4 inhibitor, and metformin may be administered together,
      separately or in fixed-dose combination (FDC), either as saxagliptin added to
      metformin or as initial combination in drug-naive patients. Both compounds exert
      complementary pharmacodynamic actions leading to better improvement in blood
      glucose control (fasting plasma glucose, postprandial glucose, HbA1c) than either
      compound separately. Adding saxagliptin to metformin monthotherapy results in a
      consistent, sustained and safe reduction in HbA1c levels. Tolerance is excellent
      without hypoglycemia or weight gain. EXPERT OPINION: The combination saxaglitpin
      plus metformin may be used as first-line or second-line therapy in the management
      of type 2 diabetes, especially as a valuable alternative to the classical
      metformin-sulfonylurea combination.

PMID- 22149375
TI  - Brain edema.

PMID- 22149376
TI  - Pharyngeal motor evoked potentials elicited by transcranial electrical
      stimulation for intraoperative monitoring during skull base surgery.
AB  - OBJECT: The purpose of this study was to determine whether monitoring of
      pharyngeal motor evoked potentials (PhMEPs) elicited by transcranial electrical
      stimulation during skull base tumor surgery might be useful for predicting
      postoperative swallowing deterioration. METHODS: The authors analyzed PhMEPs in
      21 patients during 22 surgical procedures for the treatment of skull base tumors.
      Corkscrew electrodes positioned at C3 or C4 and Cz were used to deliver
      supramaximal stimuli (220-550 V). Pharyngeal MEPs were recorded from the
      posterior wall of the pharynx through a modified endotracheal tube. The
      correlation between the final/baseline PhMEP ratio and postoperative swallowing
      function was examined. RESULTS: Postoperative swallowing function was
      significantly (p < 0.05), although not strongly (r = -0.47), correlated with the
      final/baseline PhMEP ratio. A PhMEP ratio < 50% was recorded during 4 of 22
      procedures; in all 4 of these cases, the patients experienced postoperative
      deterioration of swallowing function. After 18 procedures, the PhMEP ratios
      remained > 50%; nevertheless, after 4 (22.2%) of these 18 procedures, patients
      showed deterioration of swallowing function. CONCLUSIONS: Intraoperative PhMEP
      monitoring can be useful for predicting swallowing deterioration following skull
      base surgery, especially in patients with swallowing disturbances that are mainly
      due to reduction in the motor functions of the pharyngeal muscles.

PMID- 22149377
TI  - Accelerated axon outgrowth, guidance, and target reinnervation across nerve
      transection gaps following a brief electrical stimulation paradigm.
AB  - OBJECT: Regeneration of peripheral nerves is remarkably restrained across
      transection injuries, limiting recovery of function. Strategies to reverse this
      common and unfortunate outcome are limited. Remarkably, however, new evidence
      suggests that a brief extracellular electrical stimulation (ES), delivered at the
      time of injury, improves the regrowth of motor and sensory axons. METHODS: In
      this work, the authors explored and tested this ES paradigm, which was applied
      proximal to transected sciatic nerves in mice, and identified several novel and
      compelling impacts of the approach. Using thy-1 yellow fluorescent protein mice
      with fluorescent axons that allow serial in vivo tracking of regeneration, the
      morphological, electrophysiological, and behavioral indices of nerve regrowth
      were measured. RESULTS: The authors show that ES is associated with a 30%-50%
      improvement in several indices of regeneration: regrowth of axons and their
      partnered Schwann cells across transection sites, maturation of regenerated
      fibers in gaps spanning transection zones, and entry of axons into their muscle
      and cutaneous target zones. In parallel studies, the authors analyzed adult
      sensory neurons and their response to extracellular ES while plated on a novel
      microelectrode array construct designed to deliver the identical ES paradigm used
      in vivo. The ES accelerated neurite outgrowth, supporting the concept of a neuron
      autonomous mechanism of action. CONCLUSIONS: Taken together, these results
      support a robust role for brief ES following peripheral nerve injuries in
      promoting regeneration. Electrical stimulation has a wider repertoire of impact
      than previously recognized, and its impact in vitro supports the hypothesis that
      a neuron-specific reprogrammed injury response is recruited by the ES protocol.

PMID- 22149378
TI  - A novel method of intracranial injection via the postglenoid foramen for brain
      tumor mouse models.
AB  - OBJECT: Mouse models have been widely used in developing therapies for human
      brain tumors. However, surgical techniques such as bone drilling and skin
      suturing to create brain tumors in adult mice are still complicated. The aim of
      this study was to establish a simple and accurate method for intracranial
      injection of cells or other materials into mice. METHODS: The authors performed
      micro CT scans and skull dissection to assess the anatomical characteristics of
      the mouse postglenoid foramen. They then used xenograft and genetically
      engineered mouse models to evaluate a novel technique of percutaneous
      intracranial injection via the postglenoid foramen. They injected green
      fluorescent protein-labeled U87MG cells or virus-producing cells into adult mouse
      brains via the postglenoid foramen and identified the location of the created
      tumors by using bioluminescence imaging and histological analysis. RESULTS: The
      postglenoid foramen was found to be a well-conserved anatomical structure that
      allows percutaneous injection into the cerebrum, cerebellum, brainstem, and basal
      cistern in mice. The mean (+/- SD) time for the postglenoid foramen injection
      technique was 88 +/- 15 seconds. The incidence of in-target tumor formation in
      the xenograft model ranged from 80% to 100%, depending on the target site. High
      grade gliomas were successfully developed by postglenoid foramen injection in the
      adult genetically engineered mouse using virus-mediated platelet-derived growth
      factor B gene transfer. There were no procedure-related complications.
      CONCLUSIONS: The postglenoid foramen can be used as a needle entry site into the
      brain of the adult mouse. Postglenoid foramen injection is a less invasive, safe,
      precise, and rapid method of implanting cells into the adult mouse brain. This
      method can be applied to both orthotopic xenograft and genetically engineered
      mouse models and may have further applications in mice for the development of
      therapies for human brain tumors.

PMID- 22149379
TI  - Dural sinus stent placement for idiopathic intracranial hypertension.
AB  - OBJECT: The use of unilateral dural sinus stent placement in patients with
      idiopathic intracranial hypertension (IIH) has been described by multiple
      investigators. To date there is a paucity of information on the angiographic and
      hemodynamic outcome of these procedures. The object of this study was to define
      the clinical, angiographic, and hemodynamic outcome of placement of unilateral
      dural sinus stents to treat intracranial venous hypertension in a subgroup of
      patients meeting the diagnostic criteria for IIH. METHODS: Eighteen consecutive
      patients with a clinical diagnosis of IIH were treated with unilateral stent
      placement in the transverse-sigmoid junction region. All patients had
      papilledema. All 12 female patients had headaches; 1 of 6 males had headaches
      previously that disappeared after weight loss. Seventeen patients had elevated
      opening pressures at lumbar puncture. Twelve patients had opening pressures of 33
      55 cm H(2)O. All patients underwent diagnostic cerebral arteriography that showed
      venous outflow compromise by filling defects in the transverse-sigmoid junction
      region. All patients underwent intracranial selective venous pressure
      measurements across the filling defects. Follow-up arteriography was performed in
      16 patients and follow-up venography/venous pressure measurements were performed
      in 15 patients. RESULTS: Initial pressure gradients across the filling defects
      ranged from 10.5 to 39 mm Hg. Nineteen stent procedures were performed in 18
      patients. One patient underwent repeat stent placement for hemodynamic failure.
      Pressure gradients were reduced in every instance and ranged from 0 to 7 mm Hg
      after stenting. Fifteen of 16 patients in whom ophthalmological follow-up was
      performed experienced disappearance of papilledema. Follow-up arteriography in 16
      patients at 5-99 months (mean 25.3 months, median 18.5 months) showed patency of
      all stents without in-stent restenosis. Two patients had filling defects
      immediately above the stent. Four other patients developed transverse sinus
      narrowing above the stent without filling defects. One of these patients
      underwent repeat stent placement because of hemodynamic deterioration. Two of the
      other 3 patients had hemodynamic deterioration with recurrent pressure gradients
      of 10.5 and 18 mm Hg. CONCLUSIONS: All stents remained patent without restenosis.
      Stent placement is durable and successfully eliminates papilledema in
      appropriately selected patients. Continuing hemodynamic success in this series
      was 80%, and was 87% with repeat stent placement in 1 patient.

PMID- 22149380
TI  - Extended endoscopic endonasal approach.

PMID- 22149381
TI  - The efficacy of superficial temporal artery-middle cerebral artery anastomosis in
      patients with moyamoya disease complaining of severe headache.
AB  - OBJECT: Some patients with moyamoya disease complain of severe headache, which
      may be closely related to cerebral ischemia. The efficacy of superficial temporal
      artery-middle cerebral artery (STA-MCA) anastomosis in these patients was
      evaluated by clinicoradiological studies. METHODS: Of 117 consecutive patients
      with ischemic moyamoya disease, 25 complained mainly of severe headache (headache
      group) and 92 had no significant headache (nonheadache group). Intensity of
      headache was evaluated pre- and postoperatively. Furthermore, regional cerebral
      blood flow (rCBF) and cerebrovascular reactivity (CVR) were assessed pre- and
      postoperatively. RESULTS: The headache group was significantly younger than the
      nonheadache group. In a group corrected for the age distribution, preoperative
      rCBF and CVR were similar in headache and nonheadache groups. After STA-MCA
      anastomosis, 16 patients with headache experienced complete relief from headache,
      7 patients showed remarkable improvements and discontinued medications for
      headache, and the remaining 2 patients had some alleviation of headache but
      sometimes required medication. In the headache group, the postoperative rCBF was
      significantly greater than the preoperative value. The postoperative rCBF in this
      group was also significantly greater than the postoperative rCBF in the
      nonheadache group. CONCLUSIONS: These data suggest that severe headache is one of
      the main symptoms in young patients with moyamoya disease probably related to
      cerebral circulatory disturbances. An STA-MCA anastomosis is effective in
      relieving headache in patients with ischemic moyamoya disease manifesting severe
      headache, probably by improving perfusion pressure and cerebral circulation.

PMID- 22149382
TI  - Idiopathic intracranial hypertension and sinus stenting.

PMID- 22149383
TI  - Conventional blood tests in predicting influenza A (H1N1) rapidly.
AB  - PURPOSE: Although real-time reverse transcriptase-polymerase chain reactions (rRT
      PCR) are gold standard for the diagnosis of influenza A (H1N1), the results can
      be delayed up to several days, which is problematic during a pandemic. Because of
      this limitation of rRT-PCR, clinicians have often had to set a treatment plan
      that was solely based on clinical suspicion. We investigated the hematological
      and biochemical factors that are associated with rRT-PCR results, in order to
      help clinicians deal with acute febrile patients during influenza pandemics.
      METHODS: We conducted a retrospective, cross-sectional study of 465 emergency
      department patients who underwent both rRT-PCR and blood tests at the same time.
      Hematological and biochemical findings were compared between the rRT-PCR-positive
      group and rRT-PCR-negative group. RESULTS: Levels of leukocytes, hemoglobin,
      platelets, blood urea nitrogen (BUN), total bilirubin, lactate dehydrogenase,
      serum glucose, C-reactive protein (CRP), and procalcitonin were significantly
      different between the two groups in the univariate analyses. In the multivariate
      analyses, leukocyte counts <= 10.8 (* 10(9))/L [odd ratio (OR) = 8.2, sensitivity
      = 93.7%, NPV = 85.3%], BUN levels <= 7.1 MUmol/L (OR = 3.0, sensitivity = 93.7%,
      NPV = 85.3%), and CRP levels <= 60 mg/L (OR = 2.4, sensitivity = 93.7%, NPV =
      85.3%) were independently associated with positive rRT-PCR results. CONCLUSIONS:
      Leukocyte counts, BUN levels and CRP levels were important predictors of rRT-PCR
      positive results for 2009 influenza A (H1N1) in adults.

PMID- 22149384
TI  - pH-Sensitive self-propelled motion of oil droplets in the presence of cationic
      surfactants containing hydrolyzable ester linkages.
AB  - Self-propelled oil droplets in a nonequilibrium system have drawn much attention
      as both a primitive type of inanimate chemical machinery and a dynamic model of
      the origin of life. Here, to create the pH-sensitive self-propelled motion of oil
      droplets, we synthesized cationic surfactants containing hydrolyzable ester
      linkages. We found that n-heptyloxybenzaldehyde oil droplets were self-propelled
      in the presence of ester-containing cationic surfactant. In basic solution
      prepared with sodium hydroxide, oil droplets moved as molecular aggregates formed
      on their surface. Moreover, the self-propelled motion in the presence of the
      hydrolyzable cationic surfactant lasted longer than that in the presence of
      nonhydrolyzable cationic surfactant. This is probably due to the production of a
      fatty acid by the hydrolysis of the ester-containing cationic surfactant and the
      subsequent neutralization of the fatty acid with sodium hydroxide. A complex
      surfactant was formed in the aqueous solution because of the cation and anion
      combination. Because such complex formation can induce both a decrease in the
      interfacial tension of the oil droplet and self-assembly with n
      heptyloxybenzaldehyde and lauric acid in the aqueous dispersion, the prolonged
      movement of the oil droplet may be explained by the increase in heterogeneity of
      the interfacial tension of the oil droplet triggered by the hydrolysis of the
      ester-containing surfactant.

PMID- 22149385
TI  - Iontophoretic drug delivery across the nail.
AB  - INTRODUCTION: Topical drug delivery to treat nail diseases such as onychomycosis
      and psoriasis is receiving increasing attention. Topical nail delivery is
      challenged by the complicated structure of the nail and the low permeability of
      most drugs across the nail plate. Considerable effort has been directed at
      developing methods to promote drug permeation across the nail plate.
      Iontophoresis efficiently enhances molecular transport across the skin and the
      eye and is now being tested for its potential in ungual delivery. AREAS COVERED:
      This review covers the basic mechanisms of transport (electro-osmosis and 
      migration) and their relative contribution to nail iontophoresis as well as the
      key factors governing nail permselectivity and ionic transport numbers.
      Methodological issues concerning research in this area are summarized. The data
      available in vivo on nail iontophoresis of terbinafine specifically are reviewed
      in separate sections. EXPERT OPINION: Our understanding of nail iontophoresis has
      improved considerably since 2007; most decisively, the feasibility of nail
      iontophoresis in vivo has been clearly demonstrated. Future work is required to
      establish the adequate implementation of the technique so that its clinical
      efficacy to treat onychomycosis and nail psoriasis can be unequivocally
      determined.

PMID- 22149386
TI  - A tandem 1,3-H-shift-6pi-electrocyclization-cyclic 2-amido-diene intramolecular
      Diels-Alder cycloaddition approach to BCD-Ring of atropurpuran.
AB  - An approach toward the BCD-ring of atropurpuran via a sequence of allenic 1,3-H
      shift, 6pi-electron pericyclic ring closure, and intramolecular Diels-Alder
      cycloaddition of cyclic 2-amidodiene is described.

PMID- 22149388
TI  - Autophagy regulation and integration with cell signaling.
AB  - SIGNIFICANCE: Study over the past decade has revealed the critical role of
      autophagy in homeostatic and stress cell signaling. Autophagy is an intracellular
      process whereby double-membrane structures termed autophagosomes deliver cellular
      components to lysosomes for their degradation. RECENT ADVANCES: Targets of
      specific autophagy range from proteins to protein aggregates to organelles and
      intracellular pathogens. Accordingly, autophagy fulfills numerous physiological
      roles and its deregulation can underlie disease. CRITICAL ISSUES: Although
      autophagy is orchestrated by common core machinery, the discovery of distinct and
      highly varied autophagic programs reveals autophagy as a heterogeneous
      phenomenon, capable of specificity. FUTURE DIRECTIONS: Here the molecular
      mechanisms of mammalian autophagy are reviewed, including recent advances in
      unraveling of its machinery, specificity, and regulation. With our increasing
      knowledge of autophagy mechanisms and signaling roles, we begin to work towards a
      systems understanding of autophagy.

PMID- 22149387
TI  - Development of a liposome microbicide formulation for vaginal delivery of
      octylglycerol for HIV prevention.
AB  - The feasibility of using a liposome drug delivery system to formulate
      octylglycerol (OG) as a vaginal microbicide product was explored. A liposome
      formulation was developed containing 1% OG and phosphatidyl choline in a ratio
      that demonstrated in vitro activity against Neisseria gonorrhoeae, HSV-1, HSV-2
      and HIV-1 while sparing the innate vaginal flora, Lactobacillus. Two conventional
      gel formulations were prepared for comparison. The OG liposome formulation with
      the appropriate OG/lipid ratio and dosing level had greater efficacy than either
      conventional gel formulation and maintained this efficacy for at least 2 months.
      No toxicity was observed for the liposome formulation in ex vivo testing in a
      human ectocervical tissue model or in vivo testing in the macaque safety model.
      Furthermore, minimal toxicity was observed to lactobacilli in vitro or in vivo
      safety testing. The OG liposome formulation offers a promising microbicide
      product with efficacy against HSV, HIV and N. gonorrhoeae.

PMID- 22149389
TI  - Subjective caregiver burden of parents of adults with Duchenne muscular
      dystrophy.
AB  - PURPOSE: To describe subjective caregiver burden of parents of adults with
      Duchenne muscular dystrophy (DMD) and to identify factors associated with the
      level of subjective burden. METHODS: In a cross-sectional study in 80 parents of
      57 adult, severely disabled DMD patients' level of subjective caregiver burden
      was measured with the Caregiver Strain Index (CSI) and the Self Rated Burden
      Scale. A visual analogue scale was used to measure happiness. The expanded CSI
      version, the CarerQoL and open questions were used to analyse caregiving in more
      depth. In uni and multivariate analyses, associations of objective care
      characteristics, patient characteristics and caregiver characteristics with
      burden were explored. RESULTS: Parents indicated substantial burden, but valued
      giving care as being important and rewarding. Subjective burden was associated
      with received support, tracheotomy, active coping by the patient and anxiety in
      patient and parents, together explaining 34%-36% of variance. Living situation
      was not associated with experienced burden. CONCLUSIONS: Caring for an adult son
      with DMD is burdensome, but rewarding. Subjective caregiver burden of parents may
      be alleviated by adequate support and respite care, by avoiding tracheotomy and
      by intervention programs targeting anxiety and promoting active coping by the
      patient from childhood.

PMID- 22149391
TI  - Age dependent expression of melatonin membrane receptor (MT1, MT2) and its role
      in regulation of nitrosative stress in tropical rodent Funambulus pennanti.
AB  - Age-dependent declining level of melatonin induces free radical load and thereby
      deteriorates immune function. However, reports are lacking about age-dependent
      melatonin membrane receptor (MT1 & MT2) expression, their role in regulation of
      reactive nitrogen species (RNS) and eventually how they affect immunity of a
      tropical rodent F. pennanti. We checked MT1R, MT2R and iNOS expression in
      lymphoid organs of young middle and old aged squirrels. Nitrite and nitrate ion
      concentration (NOx) in lymphoid organs, testes and plasma, lymphocyte
      proliferation and IL-2 level was recorded. Age-dependent decrease in MT1 and MT2
      receptor expression, lymphocyte proliferation, IL-2 level and increased RNS in
      lymphoid organs, testes and plasma was observed with decreased circulatory
      melatonin. Androgen and AR expression was increased in middle-aged while declined
      in old-aged squirrels. Present study suggests that age associated
      immunosenescence is consequence of increased RNS which might have important
      relationship with melatonin membrane receptors in F. pennanti.

PMID- 22149392
TI  - Quantification of specific anion binding to non-ionic Triton X-100 micelles.
AB  - Anion binding to nonionic micelles was quantified by self-diffusion. Four anions
      were probed by multinuclear PGSTE NMR measurements in a Triton X-100 micellar
      aqueous solution. The salt concentration used was sufficiently low to avoid any
      micellar growth affecting surface curvature. The micellar aggregates that provide
      a model surface are uncharged with hydrophilic headgroups so that electrostatic
      ion surface interactions play little or no role in prescribing specific anion
      binding. Anionic affinity to the micellar surface followed a Hofmeister series,
      (CH(3))(2)AsO(2)(-) ? CH(3)COO(-) > H(2)PO(4)(-) > F(-). The observed ion
      specificity is rationalized by calling into play the nonelectrostatic
      interactions occurring between the anions and the micellar surface.

PMID- 22149393
TI  - 'That's OK. He's a guy': a mixed-methods study of gender double-standards for
      alcohol use.
AB  - Although drinking and drunkenness have traditionally been considered masculine
      behaviours, young women's alcohol consumption has increased in recent years. This
      mixed methods study was conducted to examine the extent to which young people
      endorse gender double-standards for alcohol use--i.e., less acceptance of
      drinking and drunkenness in women than men--and how these influence men's and
      women's alcohol consumption. A sample of 731 English university students
      completed an online survey of gender role attitudes, beliefs about the gendered
      nature of alcohol use and recent alcohol consumption. Sixteen participants were
      then purposively selected for individual interviews: eight women and men with the
      most egalitarian gender role beliefs, and eight women and men with the least
      egalitarian beliefs. The two sets of data revealed that although there were few
      sex differences in actual levels of drinking or drunkenness, gender double
      standards for alcohol use persist: beer drinking, binge drinking and public
      drunkenness tended to be perceived as masculine, and even the most egalitarian
      respondents were more judgemental of women's drinking. Participants modified
      their drinking style so as to maintain a desired gender identity. Although gender
      double-standards could be a focus of interventions to encourage moderate
      drinking, such approaches could reinforce gender inequalities.

PMID- 22149394
TI  - Graphene annealing: how clean can it be?
AB  - Surface contamination by polymer residues has long been a critical problem in
      probing graphene's intrinsic properties and in using graphene for unique
      applications in surface chemistry, biotechnology, and ultrahigh speed
      electronics. Poly(methyl methacrylate) (PMMA) is a macromolecule commonly used
      for graphene transfer and device processing, leaving a thin layer of residue to
      be empirically cleaned by annealing. Here we report on a systematic study of PMMA
      decomposition on graphene and of its impact on graphene's intrinsic properties
      using transmission electron microscopy (TEM) in combination with Raman
      spectroscopy. TEM images revealed that the physisorbed PMMA proceeds in two steps
      of weight loss in annealing and cannot be removed entirely at a graphene
      susceptible temperature before breaking. Raman analysis shows a remarkable blue
      shift of the 2D mode after annealing, implying an anneal-induced band structure
      modulation in graphene with defects. Calculations using density functional theory
      show that local rehybridization of carbons from sp(2) to sp(3) on graphene
      defects may occur in the random scission of polymer chains and account for the
      blue-shift of the Raman 2D mode.

PMID- 22149395
TI  - A novel retraction instrument improves the safety of single-incision laparoscopic
      cholecystectomy in an animal model.
AB  - INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) promises
      improved cosmesis and may further minimize the invasiveness of intraabdominal
      interventions but cannot come at the expense of patient safety. This study
      describes the evaluation of a novel 5-mm instrument designed for SILC that
      maintains an equivalent critical view to that obtained with standard multiport
      laparoscopic cholecystectomy (MLC). MATERIALS AND METHODS: Sixteen animals were
      randomly assigned to one of four study arms. Four techniques for laparoscopic
      cholecystectomy were used: standard four-port MLC, three-instrument SILC (SILC
      A), three-instrument SILC using a suture for lateral retraction (SILC-B), and
      three-instrument SILC using the novel instrument for retraction (SILC-C). Each
      case was timed and video-recorded. The video was cropped to obscure the method of
      retraction and evaluated by five experienced laparoscopic surgeons blinded to the
      technique used. Each case was rated subjectively on a safety and visualization
      scale of 1-4. RESULTS: SILC-A and SILC-B cases were significantly longer in
      duration than both SILC-C and MLC cases. The safety and visualization scale
      results were lower for the SILC-A technique but were equivalent for the MLC, SILC
      B, and SILC-C techniques. CONCLUSION: This study introduces a novel instrument
      for gallbladder retraction. In this initial evaluation, the new instrument showed
      encouraging results in its ability to generate good visualization, support the
      safe critical view technique, and reduce the length of the procedure.

PMID- 22149396
TI  - Laparoscopic preconditioning protects against oxidative injury in cerulein
      induced pancreatitis rats (an experimental study).
AB  - BACKGROUND: Laparoscopic cholecystectomy, particularly in the same hospital stay,
      has been widely recommended to treat gallstone-pancreatitis over the last decade.
      Although pancreatitis produces severe oxidative injury, laparoscopy exerts an
      additional effect over that is produced by pancreatitis. The preconditioning
      phenomenon previously reported as protective in open surgery is a beneficial
      maneuver also in laparoscopic surgery. So in the present study we have tried to
      find out the effect of laparoscopic preconditioning over the pancreatitis in
      cerulein-induced pancreatitis rats. METHODS: Acute pancreatitis was induced in 24
      rats weighing between 280 and 350 g by three subcutaneous injection of 80 MUg/kg
      of body weight cerulein. A 1-cm midline laparotomy was performed for all rats,
      and then they were randomly assigned to one of the following three groups (n=8
      for each): Group I (control), Group II (laparoscopy), and Group III (laparoscopic
      preconditioning [L-Pre]). After that, a catheter was placed into the peritoneum
      for the creation of the pneumoperitoneum (Pp) in all the animals except the
      control group. The rats of Groups II and III were subjected to 60 minutes of Pp
      with 15 mm Hg intraabdominal pressure followed by 30 minutes of deflation. The L
      Pre procedure was applied to Group III immediately before the laparoscopic
      procedure. Blood samples were taken for biochemical assays. Pancreas tissue
      samples were taken for light microscope analysis. RESULTS: The light microscopy
      of the pancreas tissues revealed that cerulein injection caused edema and sparse
      inflammatory cell infiltration mimicking the edematous pancreatitis. However, the
      application of laparoscopy over the pancreatitis produced significant
      inflammatory cell infiltration, acinus vacuolization, and necrosis (in one case)
      in addition to edema. But, the laparoscopic preconditioning maneuver applied
      before the laparoscopy significantly decreased in particular acinary
      vacuolization and cell infiltration. Therefore the total sum of the
      histopathological score of the L-Pre group was significantly less than that of
      the laparoscopy group. The biochemical analysis of the groups revealed that
      laparoscopy caused significant elevation of malondialdehyde levels and decrease
      of reduced glutathione values. However, the addition of preceding preconditioning
      produced significant amelioration of these parameters. CONCLUSION: Laparoscopic
      preconditioning may be a useful method to decrease the oxidative injury in cases
      undergoing cholecystectomy for biliary pancreatitis. But, it should be emphasized
      that this was a restricted experimental study, and further clinical studies are
      needed to adopt these results into clinical settings.

PMID- 22149397
TI  - Metabolic syndrome and systemic inflammation in COPD.

PMID- 22149398
TI  - Insights into COPD comorbidities from the OLIN study and other large databases.

PMID- 22149399
TI  - Asthma, chronic obstructive pulmonary disease, and mortality in the U.S.
      population.
AB  - BACKGROUND: COPD and asthma are common diseases in the U.S. population and can
      coexist. Our goal was to determine the prevalence of self-reported, physician
      diagnosed asthma and COPD in a sample of the U.S. population and their
      association with lung function impairment and mortality. METHODS: We used
      baseline data from NHANES III and the follow-up mortality data. We used logistic
      regression and Cox Proportional Hazards models, adjusting for age, sex,
      race/ethnicity, education level, smoking status, and disease stage. RESULTS: The
      sample consisted of 15,203 subjects, of whom 4,542 died during the follow-up
      period. Coexisting COPD and asthma was reported by 357 (2.7%), COPD by 815
      (5.3%), and asthma by 709 (5.3%). Subjects with both conditions had a higher
      proportion of obstruction (30.9%) than those with COPD (24.3%), asthma (13.3%),
      or no lung disease (5.4%). In survival models adjusting for all factors except
      baseline lung function, coexisting COPD and asthma had the highest risk for
      mortality (Hazard Ratio [HR] 1.83, 95% confidence interval [CI] 1.34, 2.49),
      followed by COPD only (HR 1.44, 95% CI 1.28, 1.62), and asthma only (HR 1.16, 95%
      CI 0.94, 1.42). These affects were attenuated after controlling for baseline lung
      function: coexisting asthma and COPD (HR 1.45, 95% CI 1.06, 1.98), COPD only
      (1.28, 95% CI 1.13, 1.45), and asthma only (HR 1.04, 95% CI 0.85, 1.27).
      CONCLUSION: In this analysis, subjects who report coexisting asthma and COPD have
      a higher risk of obstruction on spirometry and a higher risk of death during
      follow-up.

PMID- 22149400
TI  - Associations between BODE index and systemic inflammatory biomarkers in COPD.
AB  - BACKGROUND: COPD is a multicomponent disease and systemic inflammation represents
      one of the possible mechanisms responsible for its systemic manifestations,
      including skeletal muscle weakness and cachexia. Fat-free mass index (FFMI) that
      reflects the skeletal muscle mass, has been shown to be associated with both
      dyspnoea and exercise capacity. We hypothesized that the multidimensional BODE
      index, that reflects the multicomponent nature of COPD, might be related to
      biomarkers of systemic inflammation. We further evaluated associations between
      FFMI and systemic inflammation. METHODS: BODE index and FFMI were calculated in
      222 stable COPD patients and 132 smokers or ex-smokers with normal lung function.
      Systemic inflammation was evaluated with the measurement of leptin, adiponectin,
      CRP, IL-6, and TNF-alpha in serum samples of COPD patients. RESULTS: In patients
      with COPD, both BODE index and FFMI presented significant positive and negative
      associations respectively with leptin levels (R(2) 0.61 and 0.65, respectively),
      whereas FFMI presented an additional negative association with the levels of TNF
      alpha (R(2) 0.38). No significant associations were observed in smokers or ex
      smokers with normal lung function. CONCLUSIONS: Both BODE index and FFMI, are
      related to the circulating levels of leptin in patients with COPD, suggesting a
      possible role for leptin in the systemic component of COPD. The additional
      association of FFMI with TNF-alpha may further support a role of systemic
      inflammation in muscle wasting in COPD.

PMID- 22149401
TI  - The association of metabolic syndrome with adipose tissue hormones and insulin
      resistance in patients with COPD without co-morbidities.
AB  - Chronic obstructive pulmonary disease (COPD) and metabolic syndrome represent
      common causes of morbidity and mortality in ageing populations. The effect of the
      co-existence of COPD and metabolic syndrome on adipose tissue hormones and
      insulin resistance as well as the differences between COPD patients with and
      without metabolic syndrome have not been adequately studied. The prevalence of
      metabolic syndrome, based on Adult Treatment Panel III (ATP III) criteria, was
      evaluated in 114 male patients with COPD without significant co-morbidities.
      Pulmonary functions tests (PFTs), arterial blood gases, quality of life and BODE
      index were assessed. Blood samples were obtained for the assessment of adipose
      tissue hormones and insulin resistance. The overall prevalence of metabolic
      syndrome was 21%, being more prevalent in earlier stages of COPD. Patients with
      COPD and metabolic syndrome were younger with higher body-mass index (BMI), had
      better pulmonary function, less static hyperinflation and air-trapping, better
      diffusing capacity for carbon monoxide and BODE index. These patients had higher
      levels of leptin, lower levels of adiponectin and increased insulin resistance,
      as expressed by HOMA index, compared with patients without metabolic syndrome.
      Metabolic syndrome was more prevalent in younger patients with less severe COPD.
      These patients may constitute a specific COPD phenotype with greater leptin to
      adiponectin imbalance and insulin resistance, despite smaller impairment in PFTs.
      The prognosis and differences of these patients compared with other COPD
      phenotypes needs to be determined in prospective studies.

PMID- 22149402
TI  - Co-morbidity in mild-to-moderate COPD: comparison to normal and restrictive lung
      function.
AB  - BACKGROUND: A relationship between local and systemic inflammation and different
      co-morbidities, such as cardiovascular, has been discussed in relation to disease
      process and prognosis in COPD. AIM: To evaluate if conditions as cardiovascular
      diseases, diabetes, chronic rhinitis and gastroesophageal reflux are
      overrepresented in COPD. METHODS: All subjects with COPD according to GOLD,
      FEV(1)/FVC<0.70, were identified (n = 993) from the clinical follow-up in 2002-04
      of the OLIN (Obstructive Lung Disease in Northern Sweden) studies' cohorts
      together with 993 gender- and age-matched reference subjects without COPD (non
      COPD, further divided into normal and restrictive lung function). Interview data
      on co-morbidity and symptoms were used. RESULTS: Cardiovascular co-morbidity,
      taken together heart disease, hypertension, stroke and intermittent claudication,
      was the most common and higher in COPD compared to in normal lung function (Nlf)
      50.1% vs 41.0% (p<0.001). The prevalence of chronic rhinitis and gastroesophageal
      reflux (GERD) was higher in COPD compared to in Nlf (43.1% vs 32.3%, p<0.001 and
      16.7% vs 12.0%, p = 0.011). In restrictive lung function the prevalence of
      chronic rhinitis, cardiovascular disease, hyperlipemia and diabetes was higher
      compared to in Nlf (41.0% vs 32.3%, p = 0.017, 59.0% vs 41.0%, p<0.001, 29.2%
      vs.12.9%, p = 0.033, 20.9% vs 8.6%, p <0.001). In COPD and heart disease, 62.5%
      had chronic rhinitis and/or GERD, while in Nlf the corresponding proportion was
      42.5%. CONCLUSION: Co-morbid conditions such as cardiovascular disease, chronic
      rhinitis and gastroesophageal reflux were common in COPD. The overlap between
      heart disease, chronic rhinitis and GERD was large in COPD. Restrictive lung
      function did also identify a population with increased disease burden.

PMID- 22149403
TI  - Does a history of exercise in COPD patients affect functional status? A study
      using a lifetime physical activity questionnaire investigates a correlation
      between exercise and functional status as evidenced by six-minute walk distance.
AB  - Recent studies have shown strong associations between chronic exercise and
      improved spirometric values. Building on these findings, we investigated whether
      habitual lifetime exercise influences six-minute walk test performance (6MWT) in
      subjects with at least 10 pack-years smoking history. The 6MWT was chosen for its
      correlation with performance on activities of daily living and predictive value
      for inactivity, morbidity and mortality in individuals with chronic obstructive
      pulmonary disease (COPD) versus spirometric values, which are less adept at
      predicting functional status. Because COPD is a global cause of disability,
      therapeutic measures that delay symptom-induced immobility are more cost
      effective versus late-stage interventional therapies. Among 49 subjects, we
      compared lifetime exercise assessed with a validated physical activity
      questionnaire with six-minute walk distances (6MWD). The American College of
      Sports Medicine's (ACSM) recommended exercise levels (30 minutes/day, 1000
      kcal/week) were used as a benchmark. Among subjects with spirometry-determined
      lung obstruction (n = 21), those who have not met at least half of ACSM
      guidelines (500 kcal/week) were classified as "Inactive," while others were
      "Active." A significant difference in 6MWD was found between Inactive and Active
      subjects: (1123.86ft vs. 1468.25ft, STDev = 210.07 vs. 240.25, p = 0.0045). This
      difference was not found in subjects without lung obstruction. Pack-years was a
      significant covariate: subjects who smoked less walked farther distances. No
      relation was found between exercise and predicted FEV(1)%. In summary, our case
      control study suggests that meeting even half of ACSM exercise guidelines could
      improve functional status in smokers if habitual exercise is adopted early in
      life.

PMID- 22149404
TI  - Are we aware of restless legs syndrome in COPD patients who are in an
      exacerbation period? Frequency and probable factors related to underlying
      mechanism.
AB  - A few previous studies have reported that the patients with chronic obstructive
      pulmonary disease (COPD) have a 29.1% to 36.8% frequency of restless legs
      syndrome (RLS). In this study, we observed RLS symptoms in patients experiencing
      COPD exacerbation to better understand the relationship between the many clinical
      parameters of COPD and the presence of RLS and to attract the attention of
      specialists on the association between the two conditions. Twenty-two male
      patients in COPD exacerbation; 17 healthy individuals were evaluated in this
      study. The patients were evaluated using the 2003 RLS symptom criteria outlined
      by the International Restless Legs Syndrome Study Groups (IRLSSG). The Pittsburgh
      Sleep Quality Index and Epworth daytime sleepiness scale were used to assess the
      sleep quality of patients. The RLS symptoms were correlated with blood levels of
      laboratory and clinical parameters. Statistical analyses were performed using
      SPSS 17.0 statistical software packet. The Pittsburgh Sleep Quality Index and
      Epworth daytime sleepiness scale scores were increased in COPD patients and
      correlated significantly with RLS symptoms. It was found that 54.5% of COPD
      patients with acute exacerbations were observed to have RLS symptoms. The
      Pittsburgh Sleep Quality Index was significantly higher in COPD patients with RLS
      symptoms compared to COPD patients without RLS symptoms (p < 0.05). We did not
      observe any significant difference in the previously reported metabolic and
      clinical parameters associated with RLS in COPD patients with and without RLS.
      RLS symptoms increase during COPD exacerbation and lead to decreased sleep
      quality.

PMID- 22149405
TI  - Perioperative short-term pulmonary rehabilitation for patients undergoing lung
      volume reduction surgery.
AB  - Although pulmonary rehabilitation is recommended for patients undergoing lung
      volume reduction surgery, the optimal method of pulmonary rehabilitation is
      unclear. The aim of this study was to determine the feasibility and safety of
      perioperative short-term pulmonary rehabilitation. We enrolled candidates for
      lung volume reduction surgery from 1999 to 2006 and retrospectively evaluated the
      feasibility and safety of perioperative short-term pulmonary rehabilitation for
      these patients. The program included the progressive exercise training on a
      treadmill for approximately 3 weeks. Two primary endpoints, feasibility and
      safety, were determined by the adherence rates of the program session and the
      adverse events. Pulmonary function and exercise capacity were evaluated at
      baseline and the termination of pre- and postoperative short-term pulmonary
      rehabilitation. Twenty-two patients were enrolled in this study. All patients
      completed our program without any serious adverse events. The mean values of
      adherence rates of the preoperative, postoperative, and overall period were,
      89.1%, 95.1%, and 92.1%, respectively. All values of pulmonary function tests,
      except for forced vital capacity, significantly improved at the termination of
      postoperative short-term pulmonary rehabilitation in comparison to those at the
      termination of preoperative short-term pulmonary rehabilitation. The values of
      the 6-minute walk distance, total exercise time, and maximal workload on
      incremental exercise test were significantly improved by preoperative short-term
      pulmonary rehabilitation, and their values were maintained until the termination
      of postoperative short-term pulmonary rehabilitation. The results indicated that
      it is both feasible and safe to perform perioperative short-term pulmonary
      rehabilitation.

PMID- 22149406
TI  - Case identification of subjects with airflow limitations using the handheld
      spirometer "Hi-CheckerTM" : comparison against an electronic desktop spirometer.
AB  - BACKGROUND: Systematic case identification has been proposed as a strategy to
      improve diagnosis rates and to enable the early detection of subjects with COPD.
      We hypothesized that case identification could be possible using the handheld
      spirometer Hi-CheckerTM. AIM: To determine how to modify the FEV(1)/FEV(6) values
      obtained using the Hi-CheckerTM to screen for cases with airflow limitation.
      METHODS: Spirometry was performed with both an electronic desktop spirometer and
      with the Hi-CheckerTM in 312 male subjects. RESULTS: The average FEV(1) (mean +/-
      SD) measured using a conventional spirometer and the Hi-CheckerTM was 2.99 +/-
      0.56L and 3.07 +/- 0.57L, respectively. These results were significantly
      different (P<0.001, paired t-test for both). This difference of -0.08 +/- 0.13L
      (95% confidence interval: -0.094-0.066L) was normally distributed, and thought to
      be random. Statistically significant correlations were found for all measurements
      between the spirometer and the Hi-CheckerTM ; the Pearson's correlation
      coefficient (R) between the FEV(1)/FVC and FEV(1)/FEV(6) values was 0.881. If one
      defines a FEV(1/)FVC smaller than 0.7 measured by the spirometer as airflow
      limitation, then a FEV(1)/FEV(6) smaller than 0.746 measured by the Hi-CheckerTM
      best matches this definition, and Cohen's kappa coefficient was 0.672.
      CONCLUSION: Although the Hi-CheckerTM estimates resembled those from conventional
      spirometry, it should be emphasized that the two methods did not produce
      identical results due to random measurement error. Although one must be careful
      about overinterpreting these results, since the Hi-CheckerTM is small and
      inexpensive, it could make a significant contribution in facilitating the case
      selection of patients with airflow limitation.

PMID- 22149407
TI  - Colored 3-dimensional analyses of respiratory resistance and reactance in COPD
      and asthma.
AB  - BACKGROUND: The forced oscillation technique (FOT) is a noninvasive method with
      which to measure respiratory system resistance (Rrs) and reactance (Xrs) at a
      wide range of frequencies during breathing at rest in a short time. The purpose
      of this study was to assess the differences in Rrs and Xrs between patients with
      chronic obstructive pulmonary disease (COPD) and asthma using a new method of FOT
      with colored 3-dimensional visualization. METHODS: Fifty-one patients with stable
      COPD and 49 patients with controlled or partly controlled asthma were enrolled.
      Whole-breath or within-breath changes of Rrs and Xrs were measured and compared
      between the diseases. RESULTS: The colored 3-dimensional images clarified the
      complex oscillatory properties of the respiratory system. Whole-breath resistance
      (the difference in Rrs at 5 and 20 Hz) and reactance (Xrs at 5 Hz and resonant
      frequency), and within-breath changes in reactance (Xrs at 5 Hz and resonant
      frequency) discriminated between patients with COPD and asthma. In multivariate
      regression analyses, inspiratory-expiratory differences in Xrs at 5 Hz
      contributed significantly to the differentiation between COPD and asthma,
      independent of age, gender, body weight, and pulmonary function. CONCLUSION: This
      new method of FOT is useful in the differential diagnosis of COPD and asthma.

PMID- 22149408
TI  - The COPD Pipeline XIII.

PMID- 22149411
TI  - Interferons in autoimmune and inflammatory diseases: regulation and roles.
AB  - Several lines of evidence strongly implicate type I interferons (IFN-alpha and
      beta) and IFN-signaling in the pathogenesis of certain autoimmune inflammatory
      diseases. Accordingly, genome-wide association studies have identified
      polymorphisms in the type I IFN-signaling pathways. Other studies also indicate
      that a feed-forward loop of type I IFN production, which involves sensing of
      cytoplasmic nucleic acids by sensors, contributes to the development of
      immunopathology. In addition, a mutually positive regulatory feedback loop
      between type I IFNs and estrogen receptor-alpha may contribute to a gender bias,
      thus resulting in an increased production of type I IFNs and associated
      immunopathology in women. Increased levels of type I IFNs have numerous
      immunomodulatory functions for both the innate and adaptive immune responses.
      Given that the IFN-beta also has some anti-inflammatory roles, identifying
      molecular links among certain genotypes, cytokine profiles, and associated
      phenotypes in patients with autoimmune inflammatory diseases is likely to improve
      our understanding of autoimmunity-associated pathogenesis and suboptimal outcomes
      following standard therapies.

PMID- 22149414
TI  - A femoral model with all relevant muscles and hip capsule ligaments.
AB  - In order to evaluate stabilisation systems in trochanteric femoral fractures with
      finite element (FE) analysis, a realistic model is required. For this purpose, a
      new model of a femur with all the relevant muscles and the hip capsule ligaments
      is set up. The pelvic and tibial bones are modelled as rigid bodies so as to take
      all the muscles attached to the femur into account. Fracture zones in the
      proximal femur are defined. Following the modelling of the geometry, the
      isotropic material behaviour and the load application, a numerical calculation of
      the femur is carried out. The static iterated FE simulation shows good agreement
      with in vivo data for the one-leg-stance phase during walking and Pauwels' one
      leg stance regarding the displacement of the femoral head (2.9 and 5.2 mm,
      respectively) and the resulting hip force (253% and 294% bodyweight,
      respectively). In the modelled fracture zones without osteosynthesis, shear is
      higher than axial strain. The reduction of shear among others could be a
      criterion for judging the quality of a stabilisation implant.

PMID- 22149415
TI  - Computational estimation of errors generated by lumping of physiologically-based
      pharmacokinetic (PBPK) interaction models of inhaled complex chemical mixtures.
AB  - Many cases of environmental contamination result in concurrent or sequential
      exposure to more than one chemical. However, limitations of available resources
      make it unlikely that experimental toxicology will provide health risk
      information about all the possible mixtures to which humans or other species may
      be exposed. As such, utilizing computational models in order to make
      toxicological predictions is a useful tool in complementing experimental efforts
      which examine mixtures in health risk assessment. This paper outlines a novel
      mathematical method which reduces the complexity of a mixtures model and
      increases computational efficiency via a biologically-based lumping methodology
      (BBLM). In contrast to previous chemical lumping methodologies, BBLM allows the
      computation of error as a measure of the difference between the lumped simulation
      based on BBLM and the full mathematical model. As a consequence, the modeler has
      the opportunity to find the optimal configuration in the tradeoff between
      simplification and accuracy in order to determine an acceptable number and
      composition of lumped chemicals. To demonstrate this method, lumped equations
      based on a typical inhalation physiologically-based pharmacokinetic (PBPK) model
      assuming a competitive inhibition interaction mechanism are developed for a
      mixture of arbitrary size. The novel methodology is further tested using
      literature data for a mixture of 10 volatile organic chemicals (VOCs). Through
      simulation of these chemicals, BBLM is shown to produce good approximations when
      compared to the unlumped simulation and experimental data.

PMID- 22149417
TI  - Safety of hepatitis B, pneumococcal polysaccharide and meningococcal
      polysaccharide vaccines in pregnancy: a systematic review.
AB  - Immunization during pregnancy has the potential to protect the mother and the
      newborn from preventable diseases. Current recommendations suggest that
      inactivated vaccines might be considered during pregnancy when the benefits
      outweigh the risks. In this review, we aimed to evaluate the safety of hepatitis
      B (HB) vaccine, pneumococcal polysaccharide vaccine (PPSV) and meningococcal
      polysaccharide vaccine (MPSV) administration during pregnancy by systematically
      reviewing the available evidence in PubMed and Scopus databases, as well as
      postmarketing surveillance data (including the Vaccine Adverse Event Reporting
      System [VAERS] database). A total of 18 studies were eligible for inclusion in
      the review. Six studies provided data on HB vaccine, six on PPSV and three on
      MPSV; three additional studies compared PPSV with MPSV. Additionally, 91 reports
      on vaccinations of pregnant women were identified from postmarketing surveillance
      data (88 on HB vaccine, 2 on PPSV, 1 on MPSV). The most common complaints were
      local reactions, including tenderness and swelling. Overall, immunization during
      pregnancy did not seem to be associated with a teratogenic effect on the fetus,
      preterm labour or spontaneous abortion. However, the lack of randomized, placebo
      controlled trials, or even large cohort studies, in addition to the inherent
      limitations of the reviewed observational studies with small statistical power,
      precluded safe conclusions. Large, prospective, population-based cohort studies
      are needed to elucidate this issue.

PMID- 22149412
TI  - A cytokine-centric view of the pathogenesis and treatment of autoimmune
      arthritis.
AB  - Cytokines are immune mediators that play an important role in the pathogenesis of
      rheumatoid arthritis (RA), an autoimmune disease that targets the synovial
      joints. The cytokine environment in the peripheral lymphoid tissues and the
      target organ (the joint) has a strong influence on the outcome of the initial
      events that trigger autoimmune inflammation. In susceptible individuals, these
      events drive inflammation and tissue damage in the joints. However, in resistant
      individuals, the inflammatory events are controlled effectively with minimal or
      no overt signs of arthritis. Animal models of human RA have permitted
      comprehensive investigations into the role of cytokines in the initiation,
      progression, and recovery phases of autoimmune arthritis. The discovery of
      interleukin-17 (IL-17) and its association with inflammation and autoimmune
      pathology has reshaped our viewpoint regarding the pathogenesis of arthritis,
      which previously was based on a simplistic T helper 1 (Th1)-Th2 paradigm. This
      review discusses the role of the newer cytokines, particularly those associated
      with the IL-17/IL-23 axis in arthritis. Also presented herein is the emerging
      information on IL-32, IL-33, and IL-35. Ongoing studies examining the role of the
      newer cytokines in the disease process would improve understanding of RA as well
      as the development of novel cytokine inhibitors that might be more efficacious
      than the currently available options.

PMID- 22149419
TI  - Experiences with adverse drug reaction reporting by patients: an 11-country
      survey.
AB  - BACKGROUND: Patients are important stakeholders in pharmacovigilance; however,
      little formal evaluation has been undertaken of existing patient reporting
      schemes within and outside Europe. If patient reporting is to be recognized as
      beneficial for pharmacovigilance and further optimized, methodology and best
      practice must be internationally shared and promoted. OBJECTIVE: This study aims
      to review the methods of patient reporting of adverse drug reactions (ADRs) in 11
      countries worldwide and to compare different aspects of their experiences.
      METHODS: A survey based on telephone interviews, e-mail discussions and field
      visits of existing practices in consumer and patient reporting of ADRs was
      performed in the second half of 2010. RESULTS: The start dates of the patient
      reporting schemes vary from 1964 (Australia) to 2010 (Norway). The number of
      patient reports per country varies widely. Most countries would ideally spend
      more resources on making the public aware of the possibility that patients can
      report ADRs. Most countries have three different ways for patients to report ADRs
      - a paper form, an electronic form on a website or by telephone. The level of
      sophistication of the electronic forms varies. The route of handling of patients'
      and healthcare professionals' ADR reports is the same for most countries.
      Personalized feedback on the reported association for each report is only given
      by four organizations. All countries have guidelines for the identification of
      patients in the database and most undertake checks for duplicate reports. In all
      countries, with the exception of Norway, it is possible to ask patients for
      follow-up. None of the organizations seek medical confirmation for each patient
      report. There is a difference between countries that do a causality assessment
      for each incoming ADR report and countries that only do a causality assessment of
      reports when they are looking at a potential signal. All countries assess the
      seriousness of reports, mostly by using the criteria of the CIOMS committee. In
      all countries, patient reports are used for signal detection purposes and in
      publications about ADRs. The Netherlands and the UK are actively evaluating their
      patient reporting schemes. None of the organizations hired additional staff when
      they started with patient reporting. CONCLUSIONS: This study provides a
      comprehensive review on the methods used in patient reporting of ADRs. Although
      there are some differences in the way various countries handle patient reports of
      ADRs, the importance of giving the public the opportunity to report and the
      additional scientific value of the collected data is widely recognized by the
      countries who participated in this survey.

PMID- 22149420
TI  - Glucose-6-phosphate dehydrogenase deficiency and safety of methylene blue.

PMID- 22149418
TI  - Cardiovascular events in patients taking varenicline: a case series from
      intensive postmarketing surveillance in New Zealand.
AB  - BACKGROUND: The smoking cessation medicine varenicline has been associated with
      an increased risk of cardiovascular adverse events compared with placebo in
      clinical trials. Cases of cardiovascular events, including myocardial infarction
      (MI) and cardiac dysrhythmias, have been noted from spontaneous reporting
      systems. OBJECTIVE: The aim of this study was to summarize and describe
      cardiovascular adverse reactions identified in a general population during
      intensive postmarketing surveillance of varenicline in New Zealand. METHODS:
      Observational prospective cohort study using prescription event monitoring
      methods. The patient cohort was established from pharmacy dispensing data sent
      directly to the Intensive Medicines Monitoring Programme (IMMP) for all New
      Zealand patients prescribed varenicline. Adverse cardiovascular events were
      identified from follow-up questionnaires completed by doctors, spontaneous
      reports and by record linkage to national datasets. Cardiovascular events were
      organized into clinical groupings for further clinical assessment, and key cases
      were identified. RESULTS: All New Zealand patients dispensed a prescription for
      varenicline from 1 April 2007 to 30 November 2010 were included in this study. At
      31 January 2011, the IMMP varenicline events dataset included a total of 172
      adverse events in the IMMP circulatory System Organ Class. There were 48 reports
      of myocardial ischaemia, including 12 reports of MI and 8 reports of angina. Two
      key cases of myocardial ischaemia suggested that this may have been induced by
      coronary artery spasm secondary to varenicline treatment. There were 50 reports
      of hypotensive events, with two key cases having documented hypotension
      associated with chest pain/tightness, and a further 27 reports of dysrhythmia
      events, including two unexplained sudden deaths. CONCLUSIONS: This paper presents
      a series of cases of cardiovascular events in patients taking varenicline. Whilst
      there were multiple confounding factors in some patients, key cases were
      identified that suggested a possible mechanism of dysregulation of blood pressure
      leading to vasospasm or hypotension.

PMID- 22149422
TI  - Impact of diblock copolymers on droplet coalescence, emulsification, and
      aggregation in immiscible homopolymer blends.
AB  - Using rheo-optical techniques, we investigated the impact of interfacial wetting
      of symmetric diblock copolymers (BCPs) on the coalescence and aggregation of
      polydimethylsiloxane (PDMS) droplets in immiscible polyethylene-propylene (PEP)
      homopolymers. Anionic polymerization was used to synthesize well-defined matrix
      homopolymers and symmetric 16 kg/mol-to-16 kg/mol PDMS-b-PEP diblock copolymers
      with low polydispersity (PDI ~ 1.02) as characterized with size exclusion
      chromatography and nuclear magnetic resonance spectroscopy. Blends were
      formulated to match the viscosities between the droplets and the matrix.
      Moreover, molecular weights of these components were varied to ensure that the
      inner block of the copolymer inside the droplet was collapsed and dry, whereas
      the outer block of the copolymer outside of the droplet was stretched and wet.
      Droplet breakup and coalescence as well as interfacial tensions were measured
      using rheo-optical experiments with Linkam shearing stage and an optical
      microscope. Subsequent to droplet breakup at high shear rates, we found that the
      BCPs mitigated shear-induced coalescence at lower shear rates. Based on surface
      tension measurements, the stretching of the BCP increased in lower molecular
      weight matrices, causing the droplet surface to saturate at lower coverage in
      line with theoretical predictions. Droplet aggregation was detected with further
      reductions in shear rate, which was attributed to the dewetting or the expulsion
      of the matrix from a saturated brush. Ultimately, the regions of droplet
      coalescence and aggregation were scaled by balancing the forces of shear with
      those due to the attraction between BCP-coated droplets.

PMID- 22149425
TI  - Molecular thermodynamic modeling of droplet-type microemulsions.
AB  - Microemulsions are nanoheterogeneous, thermodynamically stable, spontaneously
      forming mixtures of oil and water by means of surfactants, with or without
      cosurfactants. The pledge to use small volumes of amphiphile molecules compared
      to large amounts of bulk phase modifiers in a variety of chemical and industrial
      processes, from enhanced oil recovery to biotechnology, fosters continuous
      investigation and an improved understanding of these systems. In this work, we
      develop a molecular thermodynamic theory for droplet-type microemulsions, both
      water-in-oil and oil-in-water, and provide the theoretical formulation for three
      component microemulsions. Our thermodynamic model, which is based on a direct
      minimization of the Gibbs free energy of the total system, predicts the
      structural and compositional features of microemulsions. The predictions are
      compared with experimental data for droplet size in water-alkane-didodecyl
      dimethylammonium bromide systems.

PMID- 22149423
TI  - Technetium pyrophosphate myocardial uptake and peripheral neuropathy in a rare
      variant of familial transthyretin (TTR) amyloidosis (Ser23Asn): a case report and
      literature review.
AB  - We report the fourth case of transthyretin amyloidosis (ATTR) Ser23Asn in a 41
      year-old Ecuadorian male. He has a pedigree that spans seven generations and
      involves 24 family members who suffered early cardiac death. Salient presenting
      symptoms were fatigue, shortness of breath, and peripheral neuropathy. The
      diagnosis of cardiac amyloid was confirmed by immunohistochemical staining of an
      endomyocardial biopsy, genotyping and by technetium pyrophosphate ((99m)Tc-PYP)
      scintigraphy, which remains to be established as a reliable tool to visualize
      myocardial amyloid involvement in patients with the Ser23Asn transthyretin (TTR)
      variant. The patient underwent successful combined heart and liver transplant. We
      add to the current ATTR literature that in patients with the rare Ser23Asn
      mutation, peripheral nerve in addition to cardiac involvement can occur and
      (99m)Tc-PYP scintigraphy can be used as an imaging modality to visualize
      myocardial amyloid.

PMID- 22149426
TI  - Abiraterone acetate, a first-in-class CYP17 inhibitor, establishes a new
      treatment paradigm in castration-resistant prostate cancer.

PMID- 22149428
TI  - Bevacizumab in glioblastoma multiforme.
AB  - Bevacizumab is a humanized IgG1 monoclonal antibody that selectively binds with
      high affinity to human VEGF and neutralizes VEGF' s biologic activity. Malignant
      gliomas are characterized by extensive microvascular proliferation and produce
      VEGF. Preclinical data indicate that angiogenesis is essential for the
      proliferation and survival of malignant glioma cells. Promising response rates,
      progression-free survival rates at 6 months and median overall survival in
      patients with recurrent glioblastoma multiforme (GBM) have been reported with
      bevacizumab, both in retrospective analyses and in prospective Phase II studies.
      In the pivotal randomized but noncomparative Phase II trial, a non-negligible
      percentage of patients survived beyond 1 and 2 years after the start of
      bevacizumab administration. However, randomized Phase III trial data on
      bevacizumab in recurrent GBM are lacking. Currently, bevacizumab is being studied
      in combination with temozolomide and radiation in previously untreated GBM
      patients in two large randomized Phase III trials.

PMID- 22149429
TI  - Hydroxyurea: a key player in cancer chemotherapy.
AB  - Hydroxyurea (HU) is a simple organic compound currently used as a cancer
      chemotherapeutic agent. It acts specifically on the S-phase of the cell cycle by
      inhibiting the enzyme ribonucleoside diphosphate reductase, thereby hindering the
      reductive conversion of ribonucleotides to deoxyribonucleotides and thus limiting
      de novo DNA synthesis. HU is employed in hemotological settings as a first-line
      treatment of myeloproliferative disorders, such as polycythemia vera, essential
      thrombocythemia and primary myelofibrosis, apart from having a vital role in
      combination therapy for management of malignant melanoma, head and neck cancers
      and brain tumors. It offers an advantage that the patient may take this drug on
      an ambulatory basis with minimum clinical toxicity, while some of its limitations
      include gastrointestinal disturbance and bone marrow depression. This review will
      summarize and present the overall effects of HU and its combination therapy as an
      anticancer agent.

PMID- 22149430
TI  - Use of pegylated liposomal doxorubicin in the management of platinum-sensitive
      recurrent ovarian cancer: current concepts.
AB  - Pegylated liposomal doxorubicin (PLD) was first approved for platinum-refractory
      ovarian cancer in 1999 and then received full approval for platinum-sensitive
      recurrent disease in 2005 by the US FDA. PLD remains an important therapeutic
      tool in the management of recurrent ovarian cancer in 2012. Phase-II and III
      clinical trials of single-agent PLD in patients with platinum-sensitive recurrent
      ovarian cancer have reported overall mean survival times up to 29 months. Recent
      interest in PLD/carboplatin combination therapy for patients with platinum
      sensitive recurrent ovarian cancer has been stirred from Phase-III trials
      reporting response rates, progressive-free survival and overall survival similar
      to other platinum-based combinations, but with a more favorable toxicity profile
      and convenient dosing schedule. Clinical trials combining PLD with poly (ADP
      ribose) polymerase inhibitors, triple angiokinase inhibitors and folate receptor
      inhibitors are enrolling or under development and may further augment the
      therapeutic efficacy of PLD.

PMID- 22149432
TI  - Role of canonical Wnt signaling in endometrial carcinogenesis.
AB  - While the role of Wnt signaling is well established in colorectal carcinogenesis,
      its function in gynecologic cancers has not been elucidated. Here, we describe
      the current state of knowledge of canonical Wnt signaling in endometrial cancer
      (EC), and its implications for future therapeutic targets. Deregulation of the
      Wnt/beta-catenin signaling pathway in EC occurs by inactivating beta-catenin
      mutations in approximately 10-45% of ECs, and via downregulation of Wnt
      antagonists by epigenetic silencing. The Wnt pathway is intimately involved with
      estrogen and progesterone, and emerging data implicate it in other important
      signaling pathways, such as mTOR and Hedgehog. While no therapeutic agents
      targeting the Wnt signaling pathway are currently in clinical trials, the
      preclinical data presented suggest a role for Wnt signaling in uterine
      carcinogenesis, with further research warranted to elucidate the mechanism of
      action and to proceed towards targeted cancer drug development.

PMID- 22149431
TI  - Development of targeted therapy in uterine serous carcinoma, a biologically
      aggressive variant of endometrial cancer.
AB  - Endometrial cancer (EC) is the most common female genital malignancy in the USA.
      Most carcinomas arising from the uterus are estrogen dependent and are associated
      with obesity and hypertension. They are designated type I ECs and typically, due
      to their early diagnosis secondary to postmenopausal bleeding, have a good
      prognosis. By contrast, type II ECs develop in older patients, are not hormone
      dependent and are responsible for most recurrences and deaths from EC. Uterine
      serous cancer constitutes up to 10% of all endometrial tumors, and represents the
      most biologically aggressive variant of type II EC. This article will describe
      the most salient molecular markers that have been identified in uterine serous
      cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a
      series of therapeutic markers for the treatment of this highly-aggressive subset
      of ECs.

PMID- 22149433
TI  - Efficacy of instillations with chemotherapy or immunotherapy following endoscopic
      resection for upper tract urothelial carcinoma.
AB  - Although nephroureterectomy with a bladder cuff remains the gold-standard
      approach to upper tract urothelial carcinoma (UTUC), the relative ease by which
      local control can be achieved for non-muscle-invasive bladder urothelial
      carcinoma keeps prompting us to look into less radical and invasive methods of
      treating UTUC. The success of transurethral bladder tumor resection followed by
      intravesical therapy in controlling noninvasive bladder cancer has been firmly
      established. However, owing to the scarcity of patients with UTUC, there are only
      a few reports on the efficacy of percutaneous or endoscopic resection followed by
      instillation with chemotherapy or immunotherapy for UTUC, most of which have
      extrapolated data from bladder cancer in deciding on treatment regimens. The
      following manuscript portrays a comprehensive review of the literature on upper
      tract instillations in patients with UTUC.

PMID- 22149434
TI  - Focal therapy for prostate cancer: patient selection and evaluation.
AB  - Recent stage migration toward low-risk prostate cancer, overtreatment of
      biologically insignificant tumors with radical prostatectomy at the additional
      expense of a non-negligible morbidity and undertreatment of patients improperly
      selected for active surveillance are the main reasons that have fueled the
      concept of focal therapy. Optimal selection of patients is the key for the
      successful implementation of focal therapy. Selection criteria for focal therapy
      vary widely and depend on clinical, histological and imaging characteristics of
      the patients that are highlighted in this article. In addition, the rationales,
      merits and limitations of the available methods for the assessment of potential
      candidates, the evaluation of treatment efficacy and follow-up of these patients
      are discussed.

PMID- 22149435
TI  - Urothelial cancers: using biology to improve outcomes.
AB  - Urothelial carcinoma (transitional cell carcinoma) is the most common malignancy
      of the urinary tract. Urothelial carcinoma of the bladder is a common disease but
      has traditionally been underrepresented in both public awareness and cancer
      research. The purpose of this review is to provide an outline of the recent
      updates in understanding of urothelial cancer etiology, particularly with regards
      to lower tract muscle-invasive disease, and to discuss the identified mutations
      in high- and low-grade disease. We will consider evidence for the current
      systemic therapies for muscle-invasive and metastatic disease and review the
      targeted therapies under investigation for advanced urothelial cancer.

PMID- 22149436
TI  - Adjuvant therapy in colon cancer.
AB  - Huge advances have been made in the treatment of colon cancer over the last
      decade. Success has been most noticeable in stage IV disease - where careful
      selection of patients with small-volume disease for treatment with surgical
      resection +/- perioperative chemotherapy has resulted in an improvement in
      survival of approximately 5-50%; and stage III - disease where the advent of 5
      fluorouracil/oxaliplatin, as adjuvant treatment has also resulted in a
      significant prolongation in survival. Progression-free survival is now an
      established surrogate for overall survival, and has resulted in more timely
      reporting of adjuvant studies and therefore faster integration of promising
      agents into the clinic. Targeted agents, which have shown promise in the
      metastatic setting, are currently being examined in the adjuvant setting,
      although results so far are disappointing. Patients with high-risk stage II
      cancer remain a challenging group. They have a poorer prognosis than those with
      stage IIIA disease, and national and international guidance recommend offering
      chemotherapy after careful discussion of the pros and cons. Despite the fact that
      we have identified many of the biological features that make stage II disease
      higher risk, we still struggle to achieve the same improvement in survival for
      this subgroup compared with others. It may be that these patients required
      treatment with alternative regimens and predictive biomarkers would be
      particularly helpful.

PMID- 22149437
TI  - Treatment of elderly patients with stage IV non-small-cell lung cancer.
AB  - Every thoracic oncologist could be considered a geriatric oncologist as the
      median age of presentation with metastatic non-small-cell lung cancer is 71
      years. Subgroup analyses and population-based studies suggest similar benefits to
      treatment of the fit elderly compared with younger patients. In 2011, a Phase III
      trial demonstrated the superiority of doublet chemotherapy over single-agent
      therapy for the elderly. For elderly patients there has been sufficient time to
      fully express any genetic predispositions, and the cumulative wear and tear,
      including the effects of cigarette smoke, can degrade performance status and
      impair organ function, leading some older patients to be less fit. Comprehensive
      geriatric assessment can augment the standard examination in defining the
      strengths and weakness of the elderly patient who is considering chemotherapy. In
      the future, biochemical assessment of physiologic age may further aid this
      assessment.

PMID- 22149438
TI  - Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma
      and an opportunity.
AB  - A major issue relating to many cancers is the absence of effective
      chemotherapeutic agents; so that most often untreatable morbidity and death are
      prevalent once the cancer has been detected and has advanced. The search for
      efficacious anticancer agents is imperative. One potential agent is zinc, which
      is decreased in the development of some cancers in order to avoid its
      cytotoxic/tumor suppressor effects on the malignant cells. This provides the
      basis and opportunity to employ a treatment regimen that restores elevated zinc
      levels in the malignant cells and elicits the cytotoxic/tumor suppressor effects
      of zinc. The enigma is that this approach and expectation has not reached
      fruition. The question is "why?". This article provides a discussion of relevant
      zinc issues that need to be considered and resolved. Important areas of research
      are identified as being essential for the successful application of zinc
      cytotoxicity/tumor suppression actions for the treatment of specific cancers.

PMID- 22149440
TI  - Normative data of a brief neuropsychological battery for Spanish individuals
      older than 49.
AB  - There is an increasing need for standardized assessment of cognition in older
      patients that is relatively brief, easy to administer, and has normative data
      adjusted for age and educational attainment. We tested 332 literate, cognitively
      normal, Spanish persons older than 49 years from the Memory Clinic of Fundacio
      ACE, Institut Catala de Neurociencies Aplicades (Barcelona, Spain) with measures
      of cognitive information processing speed, orientation, attention, verbal
      learning and memory, language, visuoperception, praxis, and executive functions.
      Several of the tests were affected by age, education, and/or gender, but the
      language of administration (i.e., Spanish or Catalan) did not affect the test
      scores. Standardized scores and percentile ranks were calculated for each age
      and/or education group for use by clinical neuropsychologists.

PMID- 22149441
TI  - The scope of early traumatic brain injury as a long-term health concern in two
      nationwide samples: prevalence and prognostic factors.
AB  - PRIMARY OBJECTIVES: To examine the scope of paediatric traumatic brain injury
      (TBI) as a health concern and to identify prognostic factors for TBI-related
      sequelae. METHODS AND PROCEDURES: The study was prospective and nationwide. A
      questionnaire was sent to a study group (SG) of all 0-19 years old in Iceland,
      diagnosed ~16 years earlier with TBI during a 1-year period, 1992-1993 (n = 550)
      and to a control group (CG) (n = 1232), selected from the National Register. MAIN
      OUTCOMES AND RESULTS: In the CG 49.5% reported having sustained TBI and 7.0%
      reported long-term disability. In the group with TBI, force of impact to the
      head, more than one incident of TBI and the injury severity by gender interaction
      predicted late symptoms. TBI severity had substantially less effect than force of
      impact and was close to non-existent for females. CONCLUSIONS: Based on two
      independent nationwide samples, the scope of TBI as a health concern in
      adolescence and young adulthood is greater than previously documented. The
      findings suggest that TBI event-related factors, especially force of impact, have
      greater predictive value than clinical symptoms of severity at the acute stage,
      females being more sensitive to the effects of mild TBI than males.

PMID- 22149442
TI  - Rehabilitation of traumatic brain injury in Italy: a multi-centred study.
AB  - OBJECTIVES: The aims of this study were to analyse TBI rehabilitation in Italy,
      identifying the main factors conditioning motor and functional recovery and
      destination upon discharge of traumatic severe acquired brain injury (sABI)
      patients who had undergone intensive rehabilitative treatment. DESIGN: An
      observational prospective study of 863 consecutive patients admitted to 52
      Rehabilitation Centres from January 2001 to December 2003. RESULTS: The main
      cause of trauma was road accidents (79.8%), the mean length of stay was 87.31 +/-
      77.26 days and 40.4% access to rehabilitation facilities after a month. Pressure
      sore rates fell from 26.1% to 6.6% during the rehabilitation programme. After
      discharge 615 patients returned home, whilst 212 were admitted to other health
      facilities. DISCUSSION: This study highlights some major criticisms of
      rehabilitation of TBI. The delay of admission and evitable complications such as
      pressure sores are correlated to a worse outcome. While LOS causes a problem of
      cost-effectiveness, the rate of home discharge is prevalent and very high
      compared with other studies.

PMID- 22149443
TI  - Comparison of subjective cognitive complaints with neuropsychological tests in
      individuals with mild vs more severe traumatic brain injuries.
AB  - PRIMARY OBJECTIVE: The aim of this study was to examine the complex inter
      relationship between subjective reports of cognitive impairments and
      neuropsychological performances in compensation-seeking individuals with
      traumatic brain injury (TBI) of differing severities. Specifically, this study
      examined: (a) the participants' neuropsychological test scores and self-reported
      ratings according to TBI severity; (b) whether there was a predictive
      relationship between self-report and cognitive test scores; and (c) the influence
      of emotional functioning on self-reported cognitive functioning. RESEARCH DESIGN:
      A multi-group comparative research design was employed. METHODS AND PROCEDURE: An
      outpatient sample of 61 patients with TBIs using neuropsychological testing, RNBI
      (Ruff Neurobehavioral Inventory) and clinical interviews. MAIN OUTCOMES AND
      RESULTS: The mild TBI group exhibited greater attentional impairments, while the
      moderate-to-severe group exhibited greater memory and learning impairments on
      neuropsychological tests. The mild group reported more cognitive symptoms than
      their more severely damaged counterparts. The mild TBI participants reported
      significantly more symptoms of post-traumatic stress disorder (PTSD).
      CONCLUSIONS: Individuals with moderate-to-severe TBI were more accurate when
      reporting their memory and learning difficulties, whereas individuals with mild
      TBI were more accurate when reporting attentional difficulties. It is likely that
      the occurrence of PTSD worsens the outcome of a mild TBI. There likely is a
      cumulative effect between the PTSD symptoms and the emotional residuals in the
      mild TBI population.

PMID- 22149444
TI  - The effect of traumatic brain injury on sustained attention and working memory.
AB  - PRIMARY OBJECTIVE: The aim of the study was to evaluate working memory (WM) and
      sustained attention (SA) following severe traumatic brain injury (TBI). RESEARCH
      DESIGN: The study was a quasi-experimental design with two dependent measures.
      METHODS AND PROCEDURES: Nine individuals with severe TBI and nine non-injured
      controls completed two visual tasks containing alphabetic stimuli: a WM task (2
      back task) and a 10-minute SA task. MAIN OUTCOMES AND RESULTS: Participants with
      TBI had lower hit rates and higher false alarm rates than controls on the WM
      task. Quantitative analysis of the group data did not reveal a differential
      deficit in SA; however, post-hoc qualitative visual analysis of individual data
      revealed considerable variability in four participants with TBI, indicating
      evidence of impaired SA in select individuals. The hit rates for both tasks were
      positively correlated, supporting the contention that WM and SA are inter
      related. CONCLUSIONS: This study provides further evidence of WM deficits
      following TBI as well as possible SA deficits in some individuals. The results
      also suggest that WM and SA are inter-related processes. Future studies are
      needed to replicate the results with larger sample sizes. Based on these
      findings, patients with TBI may present with WM and SA deficits.

PMID- 22149445
TI  - Prostacyclin treatment and clinical outcome in severe traumatic brain injury
      patients managed with an ICP-targeted therapy: a prospective study.
AB  - OBJECTIVE: To prospectively assess clinical outcome in patients with severe
      traumatic brain injury (sTBI) managed according to an ICP-targeted programme as
      well as additional treatment with prostacyclin. MATERIALS AND METHODS: Inclusion
      criteria were GCS <=8, age 15-70 years, first recorded cerebral perfusion
      pressure (CPP) > 10 mm Hg. Exclusion criteria were pregnancy, breastfeeding or
      penetrating brain injury. The patients were treated using the same ICP-guided
      protocol, with one group randomized to receive prostacyclin in a low dose (0.5 ng
      kg(-1 )min(-1)). The clinical outcome was prospectively assessed at 3, 6, 12, 18
      and 24 months using structured interviews. RESULTS: Forty-eight patients were
      included, mean age 35.5 years, median GCS 6 (3-8), 69% were multi-traumatized.
      Mortality at 3 months was 12.5%. Median Glasgow Outcome Scale (GOS) at all follow
      up points was 4. Favourable outcome (GOS 4-5) at 3 months was 52%, at 24 months
      64%. Favourable outcome increased over time. There was a statistically
      significant association between GOS, GCS at admission and age. Higher ICP(max)
      was associated with worse outcome. CONCLUSION: With this treatment protocol, a
      low number of deaths and a high number of favourable outcomes in sTBI were
      observed. Prostacyclin in this low dose does not seem to improve the outcome.
      ICP(max) is a positive predictor of worse outcome. Higher GCS at admission and
      lower age are correlated to better outcome.

PMID- 22149446
TI  - Accuracy of the S100beta protein as a marker of brain damage in traumatic brain
      injury.
AB  - INTRODUCTION: This study tested the hypothesis that S100beta is a useful
      screening tool for detecting intracranial lesion (IL) in patients with a normal
      level of consciousness after traumatic brain injury (TBI). METHODS: One hundred
      and forty-three post-TBI patients without a decrease in consciousness (GCS = 15)
      and with at least one neurological symptom (e.g. transitory loss of
      consciousness, amnesia, headache, dizziness or vomiting) were prospectively
      included. A blood sample was drawn at 6-hours post-TBI. A routine CT scan was
      obtained within 24 hours post-injury. Diagnostic properties of S100beta for IL
      prediction in CT scan findings were tested using ROC-analysis. RESULTS: A total
      of 15 patients (10.5%) had IL. Serum levels were significantly higher in these
      patients. Significant differences were found between S100beta levels and CT scan
      findings (p = 0.007). ROC-analysis showed that S100beta is a useful tool for
      detecting the presence of IL in CT scans (p = 0.007). In this series, the best
      cut-off for S100beta is 0.130 ug L(-1), with 100% sensitivity and 32.81%
      specificity. CONCLUSION: Within the first 6 hours post-TBI, serum S100beta seems
      to be an effective biochemical indicator of IL in patients without a decrease in
      consciousness. These results indicate that higher S100beta cut-off values
      substantially improve the clinical relevance of this protein.

PMID- 22149447
TI  - Differences in social participation between individuals who do and do not attend
      brain injury drop-in centres: a preliminary study.
AB  - OBJECTIVE: To compare social participation for individuals with traumatic brain
      injury (TBI) >=1 year post-injury who attend brain injury drop-in centres (BIDCs)
      with individuals who do not attend but were identified as potentially benefitting
      from attending. RESEARCH DESIGN: Cross-sectional study with 23 individuals
      attending BIDCs and a comparison group of 19 individuals not attending. KEY
      OUTCOME MEASURES: Community Integration Questionnaire, Social Provisions Scale
      and Adult Subjective Assessment of Participation. MAIN RESULTS: The comparison
      group was found to consist of 12 participants who stated that they would attend a
      BIDC ('Yes sub-group') and seven participants who stated that maybe they would
      attend a BIDC but for the most part were too busy ('Maybe sub-group'). The BIDC
      group was found to have statistically significantly higher levels of social
      participation than the comparison group and particularly the 'Yes sub-group'.
      CONCLUSIONS: Findings provide support that attendance at BIDCs may benefit social
      participation. Future directions for research are suggested.

PMID- 22149448
TI  - Bilateral extradural haematoma after acute ventricular over-drainage.
AB  - BACKGROUND: Ventricular over-drainage is a common complication of dysfunctional
      ventriculoperitoneal devices. Subdural haematomas are usually the most common
      lesions associated with that complication. Such lesions may arise after
      ventricular collapse and bridging veins disruption that follows over-drainage,
      thus contributing to distortion of brain parenchyma, increased intracranial
      hypertension and neurological decline. More rarely, extradural haematomas may
      also be observed after ventricular shunt hyperfunction and may result in rapid
      neurological decline unless a surgical procedure can be promptly performed. CASE:
      This study reports the case of a 38-old-woman who presented supratentorial
      hydrocephalus and developed bilateral extradural haematomas after the placement
      of a ventricular shunt device. Both haematomas were surgically approached and the
      dysfunctional shunt device was replaced. CONCLUSION: Extradural haematomas may
      develop precociously after ventricular over-drainage. Surgical treatment is
      mandatory and must include not only the evacuation of haematoma, but also the
      replacement of dysfunctional shunt to prevent further recurrence. The
      pathophysiology of extradural haematomas consequent of ventricular over-drainage
      and the possible use of a programmable valve to prevent these lesions are briefly
      discussed.

PMID- 22149449
TI  - Syndrome of the trephined following bifrontal decompressive craniectomy:
      implications for rehabilitation.
AB  - OBJECTIVE: The syndrome of the trephined is a rare complication observed
      following a unilateral decompressive craniectomy for traumatic brain injury. What
      has not been previously reported is the occurrence of this complication following
      a bifrontal procedure. The objective of this study was to present two clinical
      cases that serve to highlight this condition. DESIGN: A case study of two
      patients who had had a bifrontal decompressive craniectomy for severe traumatic
      brain injury. METHOD: A review was undertaken detailing the clinical course of
      the two patients. RESULTS: Both cases were young males. They had initially made
      significant improvement in their functional and cognitive performance whilst
      undergoing rehabilitation. However, after some months they demonstrated marked
      deterioration. Immediately following cranioplasty they showed considerable
      clinical improvement. CONCLUSION: If the use of bifrontal decompressive
      craniectomies continues to increase it is important that those involved in the
      rehabilitation process are familiar with this rare condition. Early recognition
      is important so that patients can receive timely intervention and it also avoids
      valuable health resources being allocated to patients who cannot receive maximal
      benefit.

PMID- 22149451
TI  - Thrombin generation and platelet activation related to subintimal percutaneous
      transluminal angioplasty.
AB  - OBJECTIVE: The purpose of this study was to measure the in vivo platelet
      activation and thrombin generation in arterial blood after passing a subintimal
      conduit. METHODS: Subintimal percutaneous transluminal angioplasty (SPTA) is a
      technique where a subintimal channel is created, allowing recanalization of long
      peripheral arterial occlusion. From 10 patients with intermittent claudication,
      undergoing successful SPTA for femoropopliteal occlusive disease, we collected
      antecubital venous blood samples immediately before treatment, preprocedural
      arterial blood samples taken at the entry level proximal to the vessel occlusion,
      and subsequently at the reentry level after successful recanalization. Venous
      follow-up blood samples were taken after 24 hours. Plasma concentrations of beta
      thromboglobulin (beta-TG), RANTES, and Prothrombin fragment (F1 + 2), were
      determined by immunoassay. Fibrinogen binding to platelets, leukocyte-platelet
      adhesion, and P-selectin were determined by flow cytometry. RESULTS: We found a
      statistically significant transluminal increase in the plasma concentrations of
      RANTES, beta-TG and F1 + 2 (p = 0.002, 0.001 and 0.001 respectively), which all
      normalized within 24 hours. Platelet-leukocyte aggregates significantly decreased
      after 24 hours compared with preprocedural and preentry levels (3.26% versus 5.26
      %, p = 0.017). P-selectin expression on circulating platelets was statistically
      significantly increased in the blood sample taken at the re-entry level compared
      with the pre-procedural and pre-entry level (p = 0.007). After 24 hours there was
      no statistically significant difference to pre-procedural levels. There was no
      significant change in platelet fibrinogen binding at any levels. CONCLUSION: When
      passing a subintimal conduit, in vivo sampled blood demonstrated an extremely
      rapid and substantial uniform platelet activation and thrombin generation.

PMID- 22149452
TI  - Effect of potassium supplementation on renal tubular function, ambulatory blood
      pressure and pulse wave velocity in healthy humans.
AB  - BACKGROUND: Potassium is the main intracellular cation, which contributes to
      keeping the intracellular membrane potential slightly negative and elicits
      contraction of smooth, skeletal and cardiac muscle. A change in potassium intake
      modifies both cardiovascular and renal tubular function. The purpose of the trial
      was to investigate the effect of dietary potassium supplementation, 100 mmol
      daily in a randomized, placebo-controlled, crossover trial of healthy
      participants during two periods of 28 days duration. The participants (N = 21)
      received a diet that was standardized regarding energy requirement, and sodium
      and water intake. METHODS: 24-hour ambulatory blood pressure (ABP) and
      applanation tonometry were used to assess blood pressure, pulse wave velocity
      (PWV), augmentation index (AIx) and central blood pressure (CBP). Immunoassays
      were used for measurements of plasma concentrations of vasoactive hormones: renin
      (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide
      (ANP), vasopressin (AVP), pro-brain natriuretic peptide (pro-BNP),endothelin
      (Endo), urinary excretions of aquaporin 2 (AQP2), cyclic AMP (cAMP), and the beta
      fraction of the epithelial sodium channel (ENaC(beta)). RESULTS: AQP2 excretion
      increased during potassium supplementation, and free water clearance fell. The
      changes in urinary potassium excretion and urinary AQP2 excretion were
      significantly and positively correlated. Aldo increased. GFR, u-ENaC- beta, PRC,
      Ang II, ANP, BNP, Endo, blood pressure and AI were not significantly changed by
      potassium supplementation, whereas PWV increased slightly. CONCLUSIONS: Potassium
      supplementation changed renal tubular function and increased water absorption in
      the distal part of the nephron. In spite of an increase in aldosterone in plasma,
      blood pressure remained unchanged after potassium supplementation.

PMID- 22149453
TI  - Stereocontrolled synthesis of the C8-C22 fragment of rhizopodin.
AB  - A convergent synthesis of the central C8-C22 core of the potent macrolide
      antibiotic rhizopodin is reported. Notable features of the stereocontrolled
      approach include an asymmetric reverse prenylation of an alcohol using a method
      of Krische, a thiazolium catalyzed transformation of an epoxyaldehyde as
      described by Bode, and a late-stage oxazole formation from advanced
      intermediates. This route demonstrates the applicability of these methodologies
      in complex natural product synthesis.

PMID- 22149454
TI  - In vitro and in vivo effects of antibiotics on bone cell metabolism and fracture
      healing.
AB  - INTRODUCTION: Recent evidence suggests that antibiotics exert direct effects on
      bone at a cellular level, disrupting mitochondrial function and cell activity.
      This comprehensive literature review aims to evaluate evidence for the effects of
      antibiotics and antimicrobials on bone and discuss the clinical implications.
      AREAS COVERED: A literature search was conducted on electronic databases covering
      a period from 1969 to 2010. Studies were included if they reported in vivo and in
      vitro experimental findings regarding the use of antibiotics and synthetic
      antibacterials in both animals and humans, focusing on bone cell function and
      especially fracture repair. EXPERT OPINION: Current research suggests that these
      negative results could be due to direct effects of antibiotics on mitochondrial
      physiology within mammalian cells. Treatment doses of antibiotics, especially
      those released from topical delivery systems such as bone cements, result in
      antibiotic concentrations thousands of times higher than those required to
      inhibit bacterial growth. Our findings suggest a need to develop current
      antibiotic delivery systems to elute sufficient doses to inhibit bacterial growth
      without negative effects on bone physiology and fracture repair processes.

PMID- 22149455
TI  - Does high load of oxidants in human semen contribute to male factor infertility?
AB  - Basal generation of reactive oxygen species (ROS) was essential for male
      reproductive function, whereas high ROS levels may be linked to low quality of
      sperm and male infertility. We examined the associations between ROS levels in
      whole ejaculates and sperm quality among 1092 male factor infertility (MFI)
      patients and 50 donors with normal semen characteristics. ROS levels were
      significantly positively correlated with abnormal morphology rate, head defect,
      and sperm deformity index. Further, we investigated whether seminal plasma from
      MFI patients with high ROS levels affects sperm motility from donors with normal
      semen characteristics. After cross-culturing fresh human sperm from donors
      possessing normal semen characteristics with seminal plasma from infertitle men,
      sperm motility was measured at different ROS levels. Seminal plasma from MFI
      patients significantly reduced motility of sperm and the reduction rate increased
      with increasing ROS levels in seminal plasma. On the other hand, we found MFI
      patients with the ROS levels in the lowest 25th percentile had similar ROS levels
      to donors with normal semen characteristics. Collectively, our observations lead
      to the hypothesis that oxidative stress plays a critical role in the development
      of MFI among those with high ROS levels, but not those with low ROS levels.

PMID- 22149456
TI  - Everyday temptations: an experience sampling study of desire, conflict, and self
      control.
AB  - How often and how strongly do people experience desires, to what extent do their
      desires conflict with other goals, and how often and successfully do people
      exercise self-control to resist their desires? To investigate desire and attempts
      to control desire in everyday life, we conducted a large-scale experience
      sampling study based on a conceptual framework integrating desire strength,
      conflict, resistance (use of self-control), and behavior enactment. A sample of
      205 adults wore beepers for a week. They furnished 7,827 reports of desire
      episodes and completed personality measures of behavioral inhibition
      system/behavior activation system (BIS/BAS) sensitivity, trait self-control,
      perfectionism, and narcissistic entitlement. Results suggest that desires are
      frequent, variable in intensity, and largely unproblematic. Those urges that do
      conflict with other goals tend to elicit resistance, with uneven success. Desire
      strength, conflict, resistance, and self-regulatory success were moderated in
      multiple ways by personality variables as well as by situational and
      interpersonal factors such as alcohol consumption, the mere presence of others,
      and the presence of others who already had enacted the desire in question.
      Whereas personality generally had a stronger impact on the dimensions of desire
      that emerged early in its course (desire strength and conflict), situational
      factors showed relatively more influence on components later in the process
      (resistance and behavior enactment). In total, these findings offer a novel and
      detailed perspective on the nature of everyday desires and associated self
      regulatory successes and failures.

PMID- 22149457
TI  - Deference in Indians' decision making: introjected goals or injunctive norms?
AB  - We examine the claim that Indians are more likely than Americans to act
      deferentially in the presence of authority figures and explore 2 possible
      psychological mechanisms for this cultural difference: introjected goals and
      injunctive norms. Studies 1 and 2 showed that after reflecting upon an
      authority's expectations, Indians were more likely than Americans to make
      clothing and course choices consistent with the authority's expectations, but
      there was no such cultural difference for peers' expectations. Study 3 showed
      that merely activating the concept of authority figures, without highlighting
      specific expectations, was sufficient to influence Indians' choices but not their
      evaluations. Examining a more basic distinction underlying introjected goals
      versus injunctive norms, Study 4 showed that authority primes influenced Indians'
      sense of what they should do but not what they want to do. Study 5 showed that,
      inconsistent with the internalized goal mechanism, the effect of explicit
      authority primes did not increase after brief delays. However, Indian
      participants who were less likely to accommodate to the salient authority
      experienced more guilt across delay conditions, which supported the injunctive
      norms mechanism. The findings suggest that manipulating injunctive norms can be
      an effective means for inducing or eliminating deferential behaviors in Indian
      settings.

PMID- 22149458
TI  - Raman spectroscopy of graphene and bilayer under biaxial strain: bubbles and
      balloons.
AB  - We use graphene bubbles to study the Raman spectrum of graphene under biaxial
      (e.g., isotropic) strain. Our Gruneisen parameters are in excellent agreement
      with the theoretical values. Discrepancy in the previously reported values is
      attributed to the interaction of graphene with the substrate. Bilayer balloons
      (intentionally pressurized membranes) have been used to avoid the effect of the
      substrate and to study the dependence of strain on the interlayer interactions.

PMID- 22149459
TI  - Development of a minimum protocol for assessment in the paediatric voice clinic.
      Part 1: evaluating vocal function.
AB  - The European Laryngological Society (ELS) recommend that functional assessment of
      voice disorder in adults requires evaluation of a number of different parameters.
      The current paper presents a discussion of four of the five parameters
      highlighted in the ELS protocol: perceptual evaluation of voice,
      videostroboscopic examination, evaluation of aerodynamic performance in voice,
      and acoustic analysis. Subjective rating of voice in children is explored in a
      companion paper. These parameters have been extensively evaluated in adults, and
      a review of the literature pertaining to the paediatric population is presented.

PMID- 22149460
TI  - Thyroid-related autoantibodies in Tunisian patients with type 1 diabetes.
AB  - AIM: To evaluate, retrospectively, the frequency of antithyroid antibodies (ATA)
      in patients with type 1 diabetes (T1D). MATERIALS AND METHODS:
      Antithyroperoxidase antibodies (TPO-Ab), antithyroglobulin antibodies (TG-Ab),
      and antithyroid-stimulating hormone receptor antibodies (TSHR-Ab) were determined
      by enzyme-linked immunosorbent assay. Sera of 312 patients (166 children and 146
      adults) with T1D were analyzed. Sera of 276 healthy subjects (87 children and 189
      blood donors) served as controls. RESULTS: Out of 312 patients with T1D, 44 (14%)
      had ATA (TPO-Ab or TG-Ab or TSHR-Ab). The frequency of ATA in patients with T1D
      was significantly higher than in the control group (14% vs. 2.8%; p<10(-5)). ATA
      were significantly more frequent in adult patients with T1D than in the blood
      donor group (20% vs. 1.6%; p<10(-8)). The frequency of ATA in adult patients was
      significantly higher than in pediatric patients (20% vs. 9%; p=0.006). The
      frequency of TPO-Ab and TG-Ab was significantly higher in patients with T1D than
      in the control group (13.5% vs. 2%; p<10(-8) and 7% vs. 2.2%, p=0.008),
      respectively. Out of 312 patients with T1D, only one had TSHR-Ab. The
      simultaneous presence of three autoantibodies was found in one patient with T1D.
      CONCLUSION: ATA were frequent in patients with T1D. Serological screening of
      autoimmune thyroid disease is suggested in patients with T1D.

PMID- 22149461
TI  - Ascorbic acid supplementation down-regulates the alcohol induced oxidative
      stress, hepatic stellate cell activation, cytotoxicity and mRNA levels of
      selected fibrotic genes in guinea pigs.
AB  - Both oxidative stress and endotoxins mediated immunological reactions play a
      major role in the progression of alcoholic hepatic fibrosis. Ascorbic acid has
      been reported to reduce alcohol-induced toxicity and ascorbic acid levels are
      reduced in alcoholics. Hence, we investigated the hepatoprotective action of
      ascorbic acid in the reversal of alcohol-induced hepatic fibrosis in male guinea
      pigs (n = 36), and it was compared with the animals abstenting from alcohol
      treatment. In comparison with the alcohol abstention group, there was a reduction
      in the activities of toxicity markers and levels of lipid and protein
      peroxidation products, expression of alpha-SMA, caspase-3 activity and mRNA
      levels of CYP2E1, TGF-beta(1), TNF-alpha and alpha(1)(I) collagen in liver of the
      ascorbic acid-supplemented group. The ascorbic acid content in liver was
      significantly reduced in the alcohol-treated guinea pigs. But it was reversed to
      normal level in the ascorbic acid-supplemented group. The anti-fibrotic action of
      ascorbic acid in the rapid regression of alcoholic liver fibrosis may be
      attributed to decrease in the oxidative stress, hepatic stellate cells
      activation, cytotoxicity and mRNA expression of fibrotic genes CYP2E1, TGF
      beta(1), TNF-alpha and alpha(1) (I) collagen in hepatic tissues.

PMID- 22149462
TI  - 'Oh, I'm just, you know, a little bit weak because I'm going to the doctor's':
      young men's talk of self-referral to primary healthcare services.
AB  - Young men visit their general practitioner (GP) less frequently than young women
      and tend to utilise primary healthcare services reluctantly. This research aimed
      to explore the ways young men used their talk to make sense of their own
      masculinity in the context of their healthcare visits, and to explore the ways
      they used their talk to make sense of those visits in terms of multiple
      masculinities and gendered behaviours. This was an important area for research as
      previous work has not focused on young men. Interviews, lasting approximately 1
      h, were conducted by a male researcher with seven men aged 22-33. Questions
      related to visiting the GP, attention to healthcare and help-seeking behaviours.
      These were analysed, using an eclectic approach informed by Foucauldian discourse
      analysis and discursive psychology. Participants subscribed to a hegemonic
      masculinity that constructed men as strong, stoical and reluctant to seek help.
      However, at times, these men negotiated and disengaged from such discourses.
      Women were constructed as immediately responding to symptoms and seeking help for
      minor illnesses. In contrast to traditional masculinity, the young men drew upon
      discourses of vulnerability and embarrassment. These results are discussed in
      relation to their implications for Health Psychology.

PMID- 22149463
TI  - Comparison of self-reported and audiometrically-measured hearing loss in the
      Australian Defence Force.
AB  - OBJECTIVE: To investigate the relationship between self-reported and
      audiometrically-measured hearing loss in a sample of Australian Defence Force
      personnel. DESIGN: Responses to a question regarding hearing problems were
      compared with contemporaneous audiometric data. STUDY SAMPLE: 3335 members of the
      Australian Defence Force for whom anonymised medical records were available.
      RESULTS: The sensitivity of self-report data to identify higher-frequency hearing
      loss was lower than sensitivity at other frequencies, and positive predictive
      values were moderate to poor at all frequencies. Performance characteristics of
      self-report compared with audiometric data also varied with age, sex, and rank.
      CONCLUSIONS: While self-report hearing loss data have good performance
      characteristics for estimating prevalence of hearing loss as defined by
      audiometric criteria, this study indicates that the usefulness of self-report
      data in identifying individuals with hearing loss may be limited in this
      population.

PMID- 22149464
TI  - Effects of functional electrical stimulation on trunk control in children with
      diplegic cerebral palsy.
AB  - PURPOSE: This study aimed to investigate the efficiency of FES application on the
      abdomen-posterior back muscles in children with CP that were enrolled into
      physical therapy and rehabilitation (PTR) program. METHOD: The study included 55
      spastic diplegic children that were hospitalized for rehabilitation. Those with
      deformities that could disrupt the balance in sitting and cause problems in
      evaluations were excluded. The patients were randomly divided into two equal
      groups according to their time of presentation. Thirty-two children completed the
      study. The control group received PTR program only for 4 weeks. The children in
      the FES group received PTR in addition to electrical stimulation. Electrical
      stimulation was applied 5 days a week for 4 weeks to abdomen-posterior back
      muscles in 30-minute-long sessions. To evaluate the balance in sitting, sitting
      score of gross motor function measurement (GMFM) and to evaluate the trunk
      asymmetry in sitting, radiographic measurements were used. Thus, kyphosis, Cobb
      and sacral angles were measured. RESULTS: The comparisons of the measurements of
      the two groups before and after the treatment showed that the GMFM sitting score
      and the sacral angle were statistically significantly increased, and the kyphotic
      and Cobb angles were statistically significantly decreased. After the treatment,
      both groups demonstrated an increase in the GMFM score, but the increase in the
      FES group was statistically significantly higher than that in the control group.
      With respect to radiological measurements, the changes observed in both the
      kyphotic and Cobb angles after the treatment were statistically significantly
      higher in the FES group than in the control group. The rates of the changes in
      the sacral angle did not differ among the groups. CONCLUSION: We believe to
      provide balance in sitting for children with CP, FES applied on abdomen-back
      muscles along with conventional therapy to maintain trunk control is more
      effective than conventional therapy alone.

PMID- 22149465
TI  - Erythema multiforme-like lesions revealing allergic contact dermatitis to exotic
      woods.
AB  - We report a 45-year old man who developed maculopapular exanthema on the inferior
      cervical folder, axillae and umbilicus, as well as erythema multiforme-like
      lesions on the wrists after the introduction in his work of pao ferro (Machaerium
      scleroxylon). Patch tests were positive to pao ferro and ebony. This case
      highlights the importance of patch tests for the confirmation of the culprit
      agent in occupational dermatoses and also to identify other occupational
      allergens that the patient should avoid. Tropical woods contain quinones that
      could explain the possible cross-reactions between woods belonging to different
      families.

PMID- 22149466
TI  - Layer-by-layer assembly of polyelectrolyte chains and nanoparticles on nanoporous
      substrates: molecular dynamics simulations.
AB  - We performed molecular dynamics simulations of a multilayered assembly of
      oppositely charged polyelectrolyte chains and nanoparticles on porous substrates
      with cylindrical pores. The film was constructed by the sequential adsorption of
      oppositely charged species in a layer-by-layer fashion from dilute solutions. The
      multilayer assembly proceeds through surface overcharging after the completion of
      each deposition step. The substrate overcharging fraction fluctuates around 0.5
      for nanoparticle-polyelectrolyte systems and around 0.4 for polyelectrolyte
      polyelectrolyte systems. The surface coverage increases linearly with the number
      of deposition steps. The rate of surface coverage increases as a function of the
      number of deposition step changes when the pore is blocked. The closing of the
      pore occurs from the pore entrance for nanoparticle-polyelectrolyte systems. In
      the case of polyelectrolyte-polyelectrolyte systems, the pore plug is formed
      inside the pore and then spreads toward the pore ends.

PMID- 22149470
TI  - The effect of methylphenidate on prefrontal cognitive functioning, inattention,
      and hyperactivity in velocardiofacial syndrome.
AB  - OBJECTIVE: Methylphenidate (MPH) is commonly used to treat attention
      deficit/hyperactivity disorder (ADHD) in all children, including those with
      velocardiofacial syndrome (VCFS). Yet concerns have been raised regarding its
      safety and efficacy in VCFS. The goal of this study was to examine the safety and
      efficacy of MPH in children with VCFS. METHODS: Thirty-four children and
      adolescents with VCFS and ADHD participated in a randomized, controlled trial
      with a 2:1 ratio of MPH versus placebo. All subjects underwent a cardiological
      evaluation before and after MPH administration. The primary outcome measure was
      prefrontal cognitive performance following a single dose of MPH or placebo. A
      follow-up assessment was conducted after a 6-month treatment with MPH. RESULTS:
      Compared with placebo, single MPH administration was associated with a more
      robust improvement in prefrontal cognitive performance, including achievements in
      the Hearts and Flowers executive function task and the visual continuous
      performance task. After 6 months of treatment, a 40% reduction in severity of
      ADHD symptoms was reported by parents on the Revised Conners Rating Scale. All
      subjects treated with MPH reported at least one side effect, but it did not
      necessitate discontinuation of treatment. MPH induced an increase in heart rate
      and blood pressure that was usually minor, but was clinically significant in two
      cases. No differences in response to MPH were observed between catechol-O
      methyltransferase Met versus Val carriers. CONCLUSION: The use of MPH in children
      with VCFS appears to be effective and relatively safe. A comprehensive
      cardiovascular evaluation for children with VCFS before and during stimulant
      treatment is recommended.

PMID- 22149471
TI  - A comparison of cartilage stress-relaxation models in unconfined compression: QLV
      and stretched exponential in combination with fluid flow.
AB  - Cartilage exhibits nonlinear viscoelastic behaviour. Various models have been
      proposed to explain cartilage stress relaxation, but it is unclear whether
      explicit modelling of fluid flow in unconfined compression is needed. This study
      compared Fung's quasi-linear viscoelastic (QLV) model with a stretched
      exponential model of cartilage stress relaxation and examined each of these
      models both alone and in combination with a fluid-flow model in unconfined
      compression. Cartilage explants were harvested from bovine calf patellofemoral
      joints and equilibrated in tissue culture for 5 days before stress-relaxation
      testing in unconfined compression at 5% nominal strain. The stretched exponential
      models fit as well as the QLV models. Furthermore, the average stretched
      exponential relaxation time determined by this model lies within the range of
      experimentally measured relaxation times for extracted proteoglycan aggregates,
      consistent with the hypothesis that the stretched exponential model represents
      polymeric mechanisms of cartilage viscoelasticity.

PMID- 22149472
TI  - Development and evaluation of sustained-release Compritol(r) 888 ATO matrix mini
      tablets.
AB  - CONTEXT: Sustained-release mini-tablets are a potentially suitable for paediatric
      drug delivery or as multi-particulate dosage forms. OBJECTIVE: To evaluate the
      potential for developing lipophilic matrix mini-tablets and to assess the effects
      of Compritol(r) 888 ATO concentration on drug release from differently sized mini
      tablets prepared by direct compression. METHODS: A formulation comprising
      theophylline as a model soluble drug, 15% w/w Compritol(r) 888 ATO as the inert
      matrix-forming agent, with dibasic dicalcium phosphate anhydrous and lactose as
      diluents was evaluated by producing 12 mm tablets at a range of compression
      speeds and forces. The same formulation and further formulations with 25, 35 or
      45% w/w Compritol(r) 888 ATO were evaluated by producing 2, 3 and 4 mm mini
      tablets. RESULTS AND DISCUSSION: Drug release from matrix tablets was sustained
      over a period of 12 hours and release rate varied according to the compression
      force and speed employed. The rate of drug release from matrix mini-tablets was
      more rapid and increasing Compritol(r) 888 ATO concentration resulted in slower
      release rates. The rate of drug release from matrix mini-tablets was inversely
      proportional to mini-tablet size (2 mm > 3 mm > 4 mm). Drug release from the
      matrix tablets and mini-tablets followed square-root of time kinetics.
      CONCLUSION: Tailored drug release from matrix mini-tablets may achieved by
      altering the size of mini-tablet or level of Compritol(r) 888 ATO in the
      formulation and this may have potential in the development of paediatric
      formulations or multi-particulate dosage forms.

PMID- 22149473
TI  - My life with LIF: a personal account of developing laser-induced fluorescence.
AB  - Laser-induced fluorescence (LIF) is a spectroscopic technique that involves the
      excitation of a molecular target by a beam of laser radiation followed by the
      detection of the subsequent emission of radiation from the target. LIF detection
      has several advantages over absorption spectroscopy. First, LIF has excellent
      detection sensitivity because a signal is observed against a dark background.
      Second, the emitted radiation can be collected at various angles with respect to
      the incoming laser beam, making it possible to obtain two- and three-dimensional
      images because the fluorescence is emitted in all directions. Third, by
      dispersing the fluorescence, it is also possible to learn about the transitions
      from the state excited to the various lower levels of the target species.
      Finally, because of the delay between the excitation and detection events, it is
      also possible to learn about what processes the excited target undergoes in the
      intervening time.

PMID- 22149474
TI  - Neural tube defects in Wales: changing demographics from 1998 to 2009.
AB  - OBJECTIVE: To establish if there is evidence for the perceived increase in the
      number of live births with a Neural tube defect (NTD) in South Wales from 1998 to
      2009. METHODS: Data was obtained from the Congenital Abnormalities Register
      Information Services (CARIS), which recorded 305 cases of pregnancies involving
      neural tube defects. Descriptive analysis was carried out for each year in this
      period to obtain the number of live births, the proportion of live births
      compared to NTD pregnancies, plus the number and the percentage terminated each
      year. RESULTS: From the 305 cases, 66 resulted in live births, 230 in
      terminations. There was an increase in live births from 13.8% in 1998 to 33.3% in
      2009, and a decrease in terminations from 82.76% in 1998 to 62.50% in 2009. The
      data also showed that this increase occurred mainly in the South of Wales.
      Discussion. Over this time period, there has been a decrease in the number of
      pregnancies affected by a neural tube defect and a decline in the proportion of
      pregnancies with neural tube defects resulting in terminations. Consequently,
      there has been an increase in the number of live births. The reasons for this
      change in trend is unclear, it may be that prospective parents are more willing
      to proceed with the pregnancy due to better support and services and the improved
      prognosis for children with neural tube defects. CONCLUSION: This data clearly
      shows that the number of children born with a NTD is increasing, and if this
      trend persists, services will have to expand and adapt to the change in the
      demographic of this population.

PMID- 22149475
TI  - Gamma knife stereotactic radiosurgery for thalamic & brainstem cavernous
      angiomas.
AB  - OBJECTIVE: To determine the safety and efficacy of Gamma Knife stereotactic
      radiosurgery (GKS) in the treatment of patients with symptomatic cavernous
      angiomas (CA) of the brainstem or thalamus, by comparing overall outcome to the
      natural history of the disease. METHODS: Over 10 years a series of 16
      consecutively presenting patients (M = 9, F = 7) with thalamic or brainstem CA
      were treated with GKS to a single lesion, specifically excluding the haemosiderin
      ring from the target. Within the year prior to treatment eight patients had
      suffered one symptomatic haemorrhage and eight had suffered more than one
      symptomatic haemorrhage. Mean age at treatment was 38.9 (15-55) years. Mean
      prescription dose 13.31 Gray (11.0 Gy-16.0 Gy). Patients were followed up
      radiologically and, more importantly, clinically for a mean period of 43.8 (11
      101) months, median 36 months. RESULTS: One patient suffered recurrent
      haemorrhage at 23 months post-GKS, but has not re-bled in the following 61
      months. One patient died of thalamic haemorrhage from the treated lesion at 90
      months. One patient was lost to follow up. There have been no other clinical
      episodes or radiological findings to suggest post-GKS haemorrhage in the
      remaining 13 patients, and no other complications were observed in the treated
      population. The annual haemorrhage rate within the first two years post GKS was
      3.72% and the annual haemorrhage rate 2 years post GKS was 3.59% per annum.
      CONCLUSION: With the dose regimens described, GKS is safe and effective in the
      treatment of thalamic and brainstem CA, as assessed by significant reduction in
      observed rate of re-haemorrhage over that expected from the known natural history
      of those CAs which have already demonstrated a tendency to haemorrhage in highly
      eloquent areas.

PMID- 22149476
TI  - Anisotropic growth of water-puckered pentamers on a mica terrace.
AB  - Ice nucleation at mica terrace edges in air forms mounds of water molecules that
      grow larger as the step-edge height increases from a few Angstroms to hundreds of
      nanometers. The structures of the ice deposits at mica terrace edges were
      characterized by atomic force microscopy (AFM), and the edges were shown to act
      as nucleators for water pentamers, thereby forming a zigzag structure with
      lattice parameters of 0.72 +/- 0.07 and 0.60 +/- 0.06 nm. A three-dimensional
      arrangement of three pentamers of water molecules, which formed a parasol-like
      structure, was assembled to match the AFM images. Seven three-fused pentamers
      were clustered to form large hexamers that cover the entire surface. The
      nucleation at the edges reveals a substantially larger growth rate than that on
      the mica terraces; consequently, highly terraced mica slabs could be used as new
      and more efficient structures for seeding clouds and causing rain. On the basis
      of this finding, a new ice-condensation structure was designed with pyramidal
      features and steps of 100 nm in height and width.

PMID- 22149477
TI  - The Brief Cognitive Assessment Tool (BCAT): a new test emphasizing contextual
      memory, executive functions, attentional capacity, and the prediction of
      instrumental activities of daily living.
AB  - The Brief Cognitive Assessment Tool (BCAT) is a new screening measure for
      cognitive dysfunction that emphasizes contextual memory and executive control
      functions. A total of 104 older adults referred for neuropsychological evaluation
      were recruited from assisted-living facilities. Psychometric analyses confirmed
      strong evidence for reliability, construct validity, and predictive validity. The
      BCAT's utility for identifying dementia versus mild cognitive impairment was
      excellent, with a sensitivity of .99, a specificity of .77, and an area under the
      receiver-operating characteristic (ROC) curve of .95. Executive control,
      contextual memory, and attentional capacity items were the best predictors of
      diagnostic category and of instrumental activities of daily living.

PMID- 22149478
TI  - Assembly behavior of iron oxide-capped Janus particles in a magnetic field.
AB  - Three types of iron oxide Janus particles are obtained by varying the deposition
      rate of iron in a 3:1 Ar/O(2) atmosphere during physical vapor deposition. Each
      type of iron oxide Janus particle shows a distinct assembly behavior when an
      external magnetic field is applied, i.e., formation of staggered chains, double
      chains, or no assembly. A detailed deposition rate diagram is obtained to
      identify the relationship between deposition rate and assembly behavior. The
      extent of iron oxidation is identified as the key parameter in determining the
      assembly behavior. In addition, the effects of particle volume fraction,
      thickness of the iron oxide cap, and assembly time on the final assembly behavior
      are studied. Cap thickness is shown not to influence the assembly behavior, while
      particle volume fraction and assembly time affect the chain growth rate and the
      chain length, but not the overall assembly behavior. The samples are
      characterized by optical, scanning electron, and atomic force microscopies.

PMID- 22149479
TI  - American Indian and Alaska Native mental health: diverse perspectives on enduring
      disparities.
AB  - As descendants of the indigenous peoples of the United States, American Indians
      and Alaska Natives (AI/ANs) have experienced a resurgence in population and
      prospects since the beginning of the twentieth century. Today, tribally
      affiliated individuals number over two million, distributed across 565 federally
      recognized tribal communities and countless metropolitan and nonreservation rural
      areas. Although relatively little evidence is available, the existing data
      suggest that AI/AN adults and youth suffer a disproportionate burden of mental
      health problems compared with other Americans. Specifically, clear disparities
      have emerged for AI/AN substance abuse, posttraumatic stress, violence, and
      suicide. The rapid expansion of mental health services to AI/AN communities has,
      however, frequently preceded careful consideration of a variety of questions
      about critical components of such care, such as the service delivery structure
      itself, clinical treatment processes, and preventive and rehabilitative program
      evaluation. As a consequence, the mental health needs of these communities have
      easily outpaced and overwhelmed the federally funded agency designed to serve
      these populations, with the Indian Health Service remaining chronically
      understaffed and underfunded such that elimination of AI/AN mental health
      disparities is only a distant dream. Although research published during the past
      decade has substantially improved knowledge about AI/AN mental health problems,
      far fewer investigations have explored treatment efficacy and outcomes among
      these culturally diverse peoples. In addition to routine calls for greater
      clinical and research resources, however, AI/AN community members themselves are
      increasingly advocating for culturally alternative approaches and opportunities
      to address their mental health needs on their own terms.

PMID- 22149480
TI  - Development, evaluation, and multinational dissemination of the triple P-Positive
      Parenting Program.
AB  - The quality of parenting children receive has a major influence on their
      development, well-being, and life opportunities. Of all the potentially
      modifiable influences that can be targeted through preventive interventions, none
      are more important than the quality of parenting children experience. Prevention
      interventions targeting parenting should be widely used to promote positive
      developmental outcomes for children and adolescents. This review argues that the
      development of comprehensive evidence-based strategies to improve the quality of
      parenting is best viewed as a major public health challenge. Using the Triple P
      Positive Parenting Program as an exemplar, the initial development, gradual
      transformation into a public health model, and then global dissemination of the
      approach is described. The assumptions underpinning the public health approach to
      parenting support are discussed, along with key criteria that need to be met for
      the approach to work. Factors that facilitate and impede the global
      implementation and dissemination of evidence-based parenting programs are
      considered along with implications for future research, policy, and practice.

PMID- 22149481
TI  - Adherence, compliance and persistence to oral antineoplastic therapy: a review
      focused on chemotherapeutic and biologic agents.
AB  - INTRODUCTION: To date, orally administered chemotherapy and biologic agents
      represent a significant percentage of all antineoplastic treatments in several
      types of cancer, which are most likely to increase in the near future. In this
      scenario, the issue of adherence and persistence to oral therapy is a key issue
      since poor compliance to oral antineoplastic treatments may negatively influence
      patients' clinical outcomes and, in turn, cause an increase in costs, number of
      hospitalizations and time spent in the hospital. AREAS COVERED: The issue of
      adherence to new oral chemotherapeutic and/or biologic agents has not been deeply
      evaluated and data published in medical literature are quite scarce. Adherence is
      a multidimensional phenomenon, which may be influenced by patient- and health
      care provider-related factors, anticancer therapy itself, education and
      socioeconomic aspects. Patients' selection plays, therefore, a key role in
      maximizing adherence and persistence to oral therapies. Treating health-care
      practitioners should first evaluate patient reliability to avoid prescribing oral
      treatments to patients with socioeconomic and medical conditions, which may
      predict poor adherence. EXPERT OPINION: Adherence and persistence to new oral
      biologic agents, which are linked to several side effects and whose use is
      constantly widening, should represent a main endpoint of clinical research in the
      nearest future.

PMID- 22149482
TI  - Evaluation of a tuberculosis whole-blood interferon-gamma chemiluminescent
      immunoassay among Chinese military recruits.
AB  - BACKGROUND AND OBJECTIVE: China is a country with a high prevalence of latent
      tuberculosis (TB) infection (LTBI) and has a policy of routine bacillus Calmette
      Guerin (BCG) vaccination. The purified protein derivative (PPD) skin test cannot
      distinguish TB infection from BCG vaccination, and the diagnosis of LTBI lacks an
      accepted standard method. The primary objective of this study was to assess the
      potential of a highly sensitive whole-blood interferon (IFN)-gamma release assay
      that uses recombinant culture filtrate protein (CFP)-10/early secretory antigenic
      target (ESAT)-6 fusion protein (rCFP-10/ESAT-6) as a stimulus for diagnosis of
      LTBI. METHODS: Between December 2009 and March 2010, a total of 892 new recruits
      to the army in Beijing, China, were interviewed and routinely examined by chest
      radiographs. IFNgamma released from whole blood in response to stimulation with
      rCFP-10/ESAT-6 was detected with an enzyme-linked chemiluminescent immunoassay.
      The recruits were also intradermally injected with PPD to assess 72-hour skin
      induration (the PPD skin test). RESULTS: Of the 892 participants, 450 (50.4%) had
      a positive PPD skin test and 244 (27.4%) had a positive whole-blood IFNgamma
      release assay. Of 442 PPD-negative subjects, 88 (19.9%) had a positive whole
      blood IFNgamma test. Of 450 PPD-positive subjects, 156 (34.7%) had a positive
      whole-blood IFNgamma test. Of 132 strongly PPD-positive subjects, 62 (47.0%) had
      a positive whole-blood IFNgamma test. The agreement between the two tests was
      57.2%. Of the 892 participants, 579 (64.9%) had clear vaccination scars on their
      arms, and of these, 382 (66.0%) had positive PPD skin responses and 162 (28.0%)
      were positive for the whole-blood IFNgamma test. CONCLUSION: The new whole-blood
      IFNgamma release assay might be a better indicator of LTBI than the PPD test in
      China.

PMID- 22149483
TI  - Electrophysiological assessment of optic nerve and retinal functions following
      intravitreal injection of bevacizumab (avastin).
AB  - PURPOSE: To evaluate the retinal and optic nerve functions of bevacizumab when
      injected intravitreal in human eyes using electrophysiological tests;
      electroretinogram (ERG) and visual evoked potentials (VEP). METHODS: Fifty-five
      eyes of 55 patients with choroidal neovascular membrane (CNV) who were prepared
      for intravitreal injections of 1.25 mg bevacizumab underwent baseline ERG and VEP
      in both eyes before, and at 1 and 6 weeks after the intravitreal injections.
      RESULTS: Mean age was 50 years ranging from 24 to 62 years, with 32 age-related
      macular degenerations and 23 myopic patients. Mean baseline best corrected visual
      acuity (BCVA) was 4/60, and mean final BCVA at 6 weeks was 6/60. There was no
      statistically significant reduction of the postinjection (1 and 6 weeks) ERG A
      and B-waves or the VEP waves' amplitudes and latency, or in the contralateral
      noninjected eyes. On the contrary, there were statistically significant
      improvement at 1 and 6 weeks in the photopic B-wave of the injected and fellow
      eyes (P values=0.046, and <0.001). CONCLUSIONS: Intravitreal bevacizumab did not
      appear to be toxic to the retina or the optic nerve at a concentration of 1.25
      mg.

PMID- 22149484
TI  - Oral Levofloxacin brings better results in treating endogenous Klebsiella
      pneumoniae endophthalmitis.

PMID- 22149485
TI  - Psychiatric nursing: back to basics.

PMID- 22149487
TI  - Studies examine pain treatment, depression ties.

PMID- 22149488
TI  - FDA-approved drugs to treat schizophrenia.

PMID- 22149490
TI  - Highly regioselective isomerization-hydroaminomethylation of internal olefins
      catalyzed by Rh complex with Tetrabi-type phosphorus ligands.
AB  - A highly regioselective isomerization-hydroaminomethylation of internal olefins
      has been developed. A 95.3% amine selectivity and 36.2 n/i ratio were obtained
      for 2-octene with a Tetrabi ligand and Rh(acac)(CO)(2), and a TON of linear amine
      was achieved of 6837 with a 39.1 n/i ratio of amine. The m-CF(3)-Ph substituted
      ligand was the best of the applied Tetrabi-type phosphorus ligands for different
      internal olefins, as up to a 99.2% amine selectivity and 95.6 n/i ratio were
      obtained for 2-pentene.

PMID- 22149492
TI  - Electrochemically supported deoxygenation of epoxides into alkenes in aqueous
      solution.
AB  - An efficient synthesis of alkenes from epoxides in a mixture of saturated aqueous
      NH(4)Br and tetrahydrofuran (8:1) has been developed in an undivided cell fitted
      with a pair of zinc electrodes, and it is proposed that the reaction is mediated
      by Zn(0) with a hierarchically organized nanostructure.

PMID- 22149493
TI  - An oral Sindbis virus replicon-based DNA vaccine containing VP2 gene of canine
      parvovirus delivered by Escherichia coli elicits immune responses in dogs.
AB  - A Sindbis virus replicon-based DNA vaccine containing VP2 gene of canine
      parvovirus (CPV) was delivered by Escherichia coli to elicit immune responses.
      The orally immunized dogs developed CPV-specific serum IgG and virus neutralizing
      antibody responses. The cellular immune responses analyzed using lymphocyte
      proliferation test and flow cytometry indicated CPV-specific sensitization of
      both CD3+CD4+ and CD3+CD8+ lymphocytes. This study demonstrated that the oral CPV
      DNA vaccine delivered by E. coli can be considered as a promising approach for
      vaccination of dogs against CPV.

PMID- 22149494
TI  - Rapid identification of YVDD mutants of hepatitis B virus using smart
      amplification process with competition probe.
AB  - Accurate and timely detection of drug-associated viral mutants is important
      during antiviral therapy. Combining Smart Amplification Process (SMAP) with
      competition probe, an assay specifically designed to detect point mutation at
      codon 204 of the hepatitis B virus (HBV) polymerase gene was developed. This
      assay was sensitive to detect 20 copies of mutant/reaction and recognize as
      little as 1% of minor mutants in the viral population. The comparison of direct
      sequencing and SMAP method on 35 clinical specimens showed the concordance in 88%
      of the cases. This method provides an efficient alternative for rapid
      identification of HBV mutation associated with lamivudine resistance.

PMID- 22149495
TI  - Characterization of a new dog isolate of canine distemper virus from China.
AB  - Canine distemper virus (CDV) is a highly contagious pathogen of dogs. Vaccination
      is an effective way to protect dogs from CDV infection, but occasionally fails.
      In the present study, a wild type (wt) CDV, named XJ2, was isolated from a dead
      vaccinated dog. The hemagglutinin (H) gene of the XJ2 was amplified and analyzed
      for the molecular characteristics including N-glycosylation sites, phylogenesis,
      hydrophobicity and epitopes. The data indicated that XJ2 was a genetic variant
      strain of CDV. CDV-sero-negative dogs were inoculated intranasally with XJ2,
      developed severe clinical symptoms and died, suggesting high virulence.

PMID- 22149496
TI  - Effect of Rta protein of Epstein-Barr virus on the cell cycle in HeLa cells.
AB  - Epstein-Barr virus (EBV) replication and transcription activator (Rta) is an
      immediate-early transcription factor that mediates the switch from latent to
      lytic infection. DNA viruses often modulate the function of critical cell cycle
      proteins to maximize the efficiency of virus replication. Here we have examined
      the effect of Rta on cell cycle progression. Cell cycle analysis revealed that
      Rta induced HeLa cells in G0/G1-phase to reenter the S-phase. Analysis of the
      expression pattern of a key set of cell cycle regulators revealed that expression
      of Rta inhibited the expression of Rb and p53 and induced the expression of E2F1.
      These findings suggest that Rta plays an active role in redirecting HeLa cell
      physiology through an Rta-mediated cell cycle transformation.

PMID- 22149497
TI  - Partial genome sequence of murine gammaherpesvirus 72 and its analysis.
AB  - Murine gammaherpesvirus 68 (MHV-68)-infected mouse is a well known model for
      studies of Epstein-Barr virus (EBV)-related lymphoproliferative diseases (LPD).
      Murine gammaherpesvirus 72 (MHV-72) has been considered a close relative of MHV
      68 but its replication in murine mammary gland cells and kinetics of infection of
      mice were found to be different. Pathological studies of a long-term-infection of
      mice revealed a similar or higher malignancy development rate in MHV-72-infected
      mice as compared with that of MHV-68. Previous comparison of MHV-72 with MHV-68
      revealed their diversity in M3, MK3, and M7 genes encoding the chemokine-binding
      protein, immune evasion protein and glycoprotein 150, respectively. In this
      study, a portion (22,899 bp) of MHV-72 genome sequence was determined, analyzed
      and compared with that of MHV-68. Nucleotide sequences of 13 structural and 6 non
      structural genes of MHV-72 and deduced amino acid sequences revealed their
      identity to those of MHV-72 except for differences in 9 nucleotides and 8 amino
      acids, occurring in 5 genes and their proteins. Due to these differences, 4
      structural proteins encoded by ORF20, ORF26, ORF48, and ORF52, respectively, and
      a non-structural protein encoded by ORF4, all of MHV-72, are predicted to have
      altered hydrophilicity and surface exposure in comparison with their MHV-68
      counterparts. These differences obviously contribute to some different
      pathogenetical features of these viruses and could explain the reduced
      immunogenicity of MHV-72 in relation to MHV-68, allowing MHV-72 to escape the
      host immune surveillance.

PMID- 22149498
TI  - Molecular characterization of sweet potato leaf curl virus (SPLCV) isolates from
      Korea: phylogenetic relationship and recombination analysis.
AB  - The complete DNA genome of sweet potato leaf curl virus (SPLCV) from samples
      obtained from eight regions was amplified by PCR and characterized in this study.
      The DNA genome of one group (SPLCV Korea group 1) consisted of 2828 nucleotides
      and that of the second group (SPLCV Korea group 2) consisted of 2829 nucleotides.
      Sequence comparisons showed that the genome sequences of SPLCV Korea isolates
      were closely related to those of SPLCV Brazil isolates (FJ969834, FJ969835, and
      FJ969836), SPLCV Japan isolate (AB433788), and SPLCV USA isolate (AF104036) with
      nucleotide sequence identity values ranging from 96-98%. Analysis of the
      phylogenetic relationship of SPLCV Korea isolates with other begomoviruses
      revealed that the majority of SPLCV Korea isolates were clustered with SPLCV
      Brazil isolates (FJ969834, FJ969835, and FJ969836). Recombination analysis
      results revealed three recombinations among SPLCV Korea isolates, SPLCV isolates
      from Brazil and Japan, and ipomoea yellow vein virus (IYVV) Italy isolate.

PMID- 22149499
TI  - Status of tobacco viruses in Serbia and molecular characterization of tomato
      spotted wilt virus isolates.
AB  - In a four-year survey to determine the presence and distribution of viruses in
      tobacco crops at 17 localities of the Vojvodina Province and Central Serbia, 380
      samples were collected and analyzed by DAS-ELISA. Out of the seven viruses
      tested, tomato spotted wilt virus (TSWV), potato virus Y (PVY), tobacco mosaic
      virus (TMV), cucumber mosaic virus (CMV), and alfalfa mosaic virus (AMV) were
      detected in 37.9, 33.4, 28.7, 23.9, and 15.5% of the total tested samples,
      respectively. TSWV was the most frequently found virus at the localities of
      Central Serbia, while PVY and CMV were the most frequent viruses in the Vojvodina
      Province. Single infections were prevalent in years 2005-2007 and the most
      frequent were those of PVY. A triple combination of those viruses was most
      frequent mixed infection type in 2008. The presence of all five detected viruses
      was confirmed in selected ELISA-positive samples by RT-PCR and sequencing. The
      comparisons of obtained virus isolate sequences with those available in NCBI,
      confirmed the authenticity of serologically detected viruses. Phylogenetic
      analysis based on partial nucleocapsid gene sequences revealed a joint clustering
      of Serbian, Bulgarian and Montenegrin TSWV isolates into one geographic
      subpopulation, which was distinct from the other subpopulation of TSWV isolates
      from the rest of the European countries. The high incidence of viruses in Serbian
      tobacco crops highlights the importance of enhancing farmers knowledge towards
      better implementation of control strategies for preventing serious losses.

PMID- 22149501
TI  - The -137G/C polymorphism of interleukin 18 promoter and risk of HIV-1 infection
      and its progression to AIDS.
AB  - A growing body of evidence suggests that host genetic factors play an important
      role both in susceptibility to human immunodeficiency virus 1 (HIV-1) infection
      and in progression to AIDS. Interleukin 18 (IL-18) is a pleiotropic
      proinflammatory cytokine that serves as an important regulator of immune
      responses. It plays a key role in induction of both Th1 and Th2 cytokines and,
      thereby, modulates their immune responses. Single nucleotide polymorphisms in the
      IL-18 gene promoter region may lead to an altered transcriptional activity and IL
      18 production, and so this may account for individuals' variation to the risk of
      HIV-1 infection. With this perspective, the -137G/C polymorphism in the promoter
      region of the IL-18 gene was studied in 500 patients with HIV-1/AIDS and an equal
      number of sex and age matched healthy controls using sequence specific polymerase
      chain reaction analysis. We did not observe any significant association of the
      heterozygous G/C genotype with the risk of HIV-1-infection/AIDS. However,
      statistically significant associations of the G allele and homozygous G/G
      genotype of -137 G/C polymorphism of IL-18 promoter with increased risk of HIV
      1/AIDS were identified. The data of the present study suggest that IL-18 -137 G
      allele and G/G genotype seem to be involved in the pathogenesis of HIV-1
      infection among North Indians.

PMID- 22149500
TI  - Genetic characterization of vaccine and field strains of serotype A foot-and
      mouth disease virus from India.
AB  - Extreme antigenic and genetic heterogeneity of serotype A foot-and-mouth disease
      virus (FMDV) population has resulted in change of vaccine strains in India twice
      in the last decade. In such a situation, complete characterization of the vaccine
      strains is imperative. With regard to the frequent outbreaks of this disease,
      FMDV field strains are also of interest. Therefore three vaccine strains and two
      field strains of type A FMDV from India were completely sequenced and the
      obtained sequences were subjected to sequence and phylogenetic analyses. Based on
      the complete coding region, all the Indian strains clustered in the Asia topotype
      and exhibited a more than 11% nt divergence from the other Asian strains. The 5'
      UTR of some Indian strains revealed block deletions of 43 and 86 nt corresponding
      to the pseudoknot region. Amino acids S44 in VP2 and F164 in VP1 were found to be
      the exclusive signatures for the Asia topotype. The vaccine strains differed at
      65 aa positions in the capsid region, 13 of them antigenically critical.
      Variability at such positions is likely to affect the antigenic profile of these
      strains. Complete genome sequences of the vaccine strains presented here could
      serve as the reference for any comparative genomics in future.

PMID- 22149502
TI  - Complete genome sequence of an isolate of Clerodendron yellow mosaic virus--a new
      begomovirus from India.
AB  - Clerodendron inerme, a common hedge plant grown in India, is affected by a yellow
      mosaic disease caused by a begomovirus. In the present study, the complete genome
      (DNA A) of this virus was cloned and sequenced. The total size of DNA A is 2760
      nucleotides. The genome of this virus contains six open reading frames and a non
      coding intergenic region of 293 nucleotides. Nucleotide sequence comparison
      analysis revealed maximum sequence identity with Papaya leaf curl virus-Pakistan
      [Pakistan:Cotton:2002] (73.9%). As this virus had less than 89% identity with
      other begomoviruses, it was identified as a new begomovirus species and
      tentatively, named as Clerodendron yellow mosaic virus-[India:New Delhi:2007]
      (ClYMV-[IN:ND:07]).

PMID- 22149503
TI  - Glycoprotein B gene-based phylogenetic analysis of porcine  cytomegalovirus
      isolates.

PMID- 22149504
TI  - An alternative and ecological source of microprojectils for biolistic DNA
      delivery into plant tissues.

PMID- 22149505
TI  - Flow cytometric analysis of intracellular IL-17A in T-cells during ectromelia
      virus infection.

PMID- 22149506
TI  - The effects of cigarette smoking on the female voice.
AB  - To investigate voice changes as they develop over time due to cigarette smoking,
      women who never smoked (NS), women who smoked less than 10 years (S1), and women
      who smoked 10 or more years (S2) were compared. Acoustic (fundamental frequency,
      jitter, shimmer, signal-to-noise ratio), electroglottographic (open, closing, and
      speed quotients), aerodynamic (subglottal pressure, airflow, laryngeal airway
      resistance), and perceptual measures were obtained. Fundamental frequency and
      open quotient significantly decreased and speed quotient significantly increased
      in S1 and S2; jitter and shimmer significantly increased in S2 only. NS were
      perceived as non-smokers more reliably than S1 and S2 as smokers. Fundamental
      frequency, open quotient, and speed quotient were the most sensitive indicators
      of smoking effects on the female voice.

PMID- 22149520
TI  - Echocardiographic evaluation of cardiac infections.

PMID- 22149516
TI  - Antioxidant and anticholinesterase effects of frequently consumed cereal grains
      using in vitro test models.
AB  - The ethyl acetate and ethanol extracts obtained from eight varieties (Faikbey, Y
      1779, CI-8357, Cheokota, Seydisehir, Y-330, Sivas and YVD-18) of oat (Avena
      sativa L.), one variety (Larende) of barley (Hordeum vulgare L.), one variety
      (Tatlicak 97) of triticale (Triticale sp.) and one rye variety (Aslim 95) (Secale
      cereale L.) were investigated for their antioxidant effects in seven test
      systems. Anticholinesterase activity of the extracts was examined by enzyme
      linked immunosorbent assay (ELISA) microplate reader. Total phenol and flavonoid
      contents were calculated using Folin Ciocalteau and AlCl3 reagents, respectively.
      All of the extracts were ineffective in cholinesterase inhibition assays and had
      weak-to-moderate activity in antioxidant assays. The extracts exerted better
      activity in iron-chelation capacity ranging between 43.17 +/- 2.04 and 62.97 +/-
      1.29%. Triticale extracts showed higher activity in reducing power experiments. A
      notable difference in the results of the antioxidant activity assays was observed
      among the oat varieties.

PMID- 22149521
TI  - Statins in coronary artery bypass grafting surgery: lipid lowering and beyond.

PMID- 22149523
TI  - Carvedilol: a third-generation beta-blocker should be a first-choice beta
      blocker.
AB  - beta-Blockers are a standard of care in many clinical settings such as acute
      myocardial infarction, heart failure and patients at risk for a coronary event.
      However, not all beta-blockers are the same and they vary in properties such as
      lipophilicity, metabolic profile, receptor inhibition, hemodynamics, tolerability
      and antioxidant/anti-inflammatory effects. It has been unclear whether these
      differences affect outcomes or if one beta-blocker should be preferred over
      another. This review will summarize the properties of metoprolol, atenolol and
      carvedilol, as well as comparative experimental and clinical trials between these
      agents. We will provide compelling evidence of why carvedilol should be a first
      line beta-blocker and why it offers many advantages over the beta1-selective beta
      blockers.

PMID- 22149525
TI  - Advances in noninvasive imaging for evaluating clinical risk and guiding therapy
      in carotid atherosclerosis.
AB  - Managing asymptomatic carotid atherosclerosis with a view to preventing ischemic
      stroke is a challenging task. As the annual risk of stroke in untreated
      asymptomatic patients on average is less than the risk of surgical intervention,
      the key question is how to identify those asymptomatic individuals whose risk of
      stroke is elevated and who would benefit from surgery, while sparing low-risk
      asymptomatic patients from the risks of surgical intervention. The advent of a
      multitude of noninvasive carotid imaging techniques offers an opportunity to
      improve risk stratification in patients and to monitor the response to medical
      therapies; assessing efficacy at individual and population levels. As part of
      this, plaque measurement techniques (using ultrasound, computed tomography or
      MRI) may be employed in monitoring plaque/component regression and progression.
      Novel imaging applications targeted to plaque characteristics, inflammation and
      neovascularization, including contrast-enhanced ultrasound and MRI, dynamic
      contrast-enhanced MRI, and fluorodeoxyglucose-PET, are also being explored.
      Ultimately, noninvasive imaging and other advances in risk stratification aim to
      improve and individualize the management of patients with carotid
      atherosclerosis.

PMID- 22149526
TI  - Evaluation of myocardial ischemia and viability by noninvasive cardiac imaging.
AB  - Noninvasive cardiac imaging plays a central role in the diagnosis of coronary
      artery disease and cardiomyopathy, as well as in the decision making for
      therapeutic interventions. Proper assessment of the degree of myocardial ischemia
      and viability is essential to aid in therapies that may improve patient outcomes.
      In addition, a wealth of evidence exists on the prognostic value of the
      information obtained from noninvasive imaging. One must utilize an imaging study
      or studies in an organized fashion, incorporating the latest scientific evidence,
      guidelines and appropriateness criteria. This review summarizes the advantages,
      disadvantages and relevant literature on various imaging modalities currently
      available for the evaluation of myocardial ischemia and viability.

PMID- 22149524
TI  - Understanding the genetics of coronary artery disease through the lens of
      noninvasive imaging.
AB  - Coronary artery disease is a common condition with a known heritable component
      that has spurred interest in genetic research for decades, resulting in a handful
      of candidate genes and an appreciation for the complexity of its genetic
      contributions. Recent advances in sequencing technologies have resulted in large
      scale association studies, possibly adding to our current understanding of the
      genetics of coronary artery disease. Sifting through the statistical noise,
      however, requires the selection of effective phenotypic markers. New imaging
      technologies have improved our ability to detect subclinical atherosclerosis in a
      safe and reproducible manner in large numbers of patients. In this article, we
      propose that advances in imaging technology have generated improved phenotypic
      markers for genetic association studies of coronary artery disease.

PMID- 22149527
TI  - Non-contrast-enhanced magnetic resonance angiography: techniques and
      applications.
AB  - Non-contrast-enhanced magnetic resonance angiography has gained renewed interest
      since the discovery of the association between gadolinium-based contrast agents
      and nephrogenic systemic fibrosis. The following article is an overview of the
      different magnetic resonance angiography sequences, the technical possibilities
      and new developments. Clinical options and recent advancements will be
      highlighted, and recommendations for non-contrast-enhanced magnetic resonance
      angiography techniques in different anatomical regions will be given.
      Furthermore, the authors seek to predict the future of non-contrast-enhanced
      magnetic resonance angiography, with special focus on patients at risk.

PMID- 22149528
TI  - Low-dose cardiac imaging: reducing exposure but not accuracy.
AB  - Cardiac imaging techniques that use ionizing radiation have become an integral
      part of current cardiology practice. However, concern has arisen that ionizing
      radiation exposure, even at the low levels used for medical imaging, is
      associated with the risk of cancer. From a single diagnostic cardiac imaging
      procedure, such risks are low. On a population basis, however, malignancies
      become more likely on account of stochastic effects being more probable as the
      number of procedures performed increases. In light of this, and owing to
      professional and industrial commitment to the as low as reasonably achievable
      (ALARA) principle, over the last decade major strides have been made to reduce
      radiation dose in cardiac imaging. Dose-reduction strategies have been most
      pronounced in cardiac computed tomography. This was important since computed
      tomography has rapidly become a widely used diagnostic alternative to invasive
      coronary angiography, and initial protocols were associated with relatively high
      radiation exposures. Advances have also been made in nuclear cardiology and in
      invasive coronary angiography, and these reductions in patient exposure have all
      been achieved with maintenance of image quality and accuracy. Improvements in
      imaging camera technology, image acquisition protocols and image processing have
      lead to reductions in patient radiation exposure without compromising imaging
      diagnostic accuracy.

PMID- 22149529
TI  - Electrocardiographic findings associated with cocaine use in humans: a systematic
      review.
AB  - Cocaine remains highly prevalent and accessible in the general population,
      continues to represent one of the most commonly reported substances in drug
      related presentations to emergency departments, and is frequently implicated in
      drug-related deaths. Fatal cardiac arrhythmias are often suspected in the latter
      cases. In spite of this, its complex effects on the human cardiac conduction
      system remain poorly elucidated. In this article we sought to systematically
      review the medical literature to identify the electrocardiographic findings that
      have been linked to cocaine use in humans in an effort to highlight what
      physicians can expect to encounter when managing patients using the drug. The
      evidence is discussed, common findings are emphasized and clinical
      recommendations are proposed.

PMID- 22149531
TI  - Empirical correlations between Krafft temperature and tail length for
      amidosulfobetaine surfactants in the presence of inorganic salt.
AB  - Long-chain amidosulfobetaine surfactants, 3-(N-fattyamidopropyl-N,N-dimethyl
      ammonium) propanesulfonates (n-DAS, n > 18), are insoluble in pure water due to
      their high Krafft temperature (T(K)), while they are soluble when inorganic salt
      is added to the surfactant solution as the T(K) of these zwitterionic surfactants
      is decreased. The influence of the salt content and ionic species of the added
      electrolytes on the T(K) of the series of amidosulfobetaine surfactants was
      examined by means of UV-vis spectrophometry and visual inspection. It was found
      that the T(K) of these surfactants depends strongly on not only the hydrophobic
      alkyl length (n), but also the salinity of the aqueous environment. When the salt
      concentration is increased from 0 to 100 mM, the T(K) shows a sharp decrease;
      when the salinity is fixed between 100 and 2000 mM, the T(K) varies linearly with
      n with a slope of ~7.7 irrespective of the salt species and the salt content.
      When the salt concentration is further increased above 2000 mM, a linear function
      is still observed, but the slope increases slightly.

PMID- 22149532
TI  - Minority talks: the influence of descriptive social norms on fruit intake.
AB  - Previous research established that norms describing the behaviour of a majority
      (e.g. 'many people consume too much alcohol') can have ironic and unwanted
      effects on health behaviour. To date, no research has addressed the effects of
      minority descriptive norms (e.g. 'only few people use sunscreen'), while such
      minority norms are frequently communicated to the public. The current studies
      investigate the effects of minority and majority norms on intended and actual
      fruit intake. University students received either minority or majority normative
      information describing fruit intake behaviour of a referent group. Identification
      strength with this referent group was measured (Study 1) or manipulated (Study
      2). Results showed that, compared to majority norms, minority norms negatively
      affected fruit intake when participants strongly identify with the referent
      group. Moreover, absolute negative (minority norm) and positive (majority norm)
      effects of one-third portion of fruit were found compared to a no-norm condition.
      Since minority norms are often communicated with the intention of alarming people
      regarding their low engagement in health protective behaviour, the potential
      ironic effects of these minority norms should be taken into account when
      presenting such information to the public.

PMID- 22149533
TI  - A cost-effectiveness analysis of reducing ventilator-associated pneumonia at a
      Danish ICU with ventilator bundle.
AB  - BACKGROUND: More than 100,000 patients each year in Denmark experience nosocomial
      infections, erroneous medication, or pressure ulcers while hospitalized. The
      Danish Safer Hospital Program includes 12 bundles for improving patient safety
      through the introduction and maintenance of evidence-based routine treatment or
      standard procedures. OBJECTIVE: To determine cost-effectiveness of implementing
      the Ventilator bundle (VB), thereby reducing ventilator-associated pneumonia
      (VAP), when treating a ventilated patient, compared to standard procedure.
      SETTING AND PATIENTS: A hypothetical population of intensive care patients in a
      Danish ICU, ventilated for >48 h. METHODS: Cost-effectiveness analysis of the
      implementation of VB. The outcomes were prevention of VAP and prevention of
      death. Model inputs were evidence based from literature along with data from
      Kolding Hospital. A hypothetical population of intensive care patients in a
      Danish ICU, ventilated for >48 h was used. RESULTS: The cost per VAP episode
      prevented was ~?4451, and cost per death prevented was ~?31,792. The incremental
      cost-effectiveness scatter plot showed that VB was more effective in 99.9%, and
      42.6% have lower cost and better outcome for prevention of VAP. The incremental
      cost-effectiveness scatter plot showed that VB was more effective in 85.9%, and
      31.6% have lower cost and better outcome for death prevented. LIMITATIONS: The
      study was a retrospective cost analysis where incidence rates were based on best
      evidence, even if it did not cover all elements in the VB. The perspective of
      this study was seen from a third-party payer, e.g., the hospital, thus societal
      costs and direct medical costs post-hospitalization for patients with VAP were
      not considered. CONCLUSION: We found that implementation of VB is potentially
      cost-effective when considering prevention of one case of VAP or death, based on
      a Danish ICU as a case study.

PMID- 22149534
TI  - Psychophysical correlates in adults with sensory modulation disorder.
AB  - PURPOSE: Individuals with sensory modulation disorder (SMD) demonstrate abnormal
      responses to naturally occurring stimuli in a manner that interferes with daily
      life activities. This study is the first study applying quantitative sensory
      testing to characterize the somatosensory sensitivity of adults with SMD. METHOD:
      One hundred and fifty one adults (68 males and 83 females) were tested comparing
      91 SMD to 60 SMD-free, control individuals. Group placement (SMD vs. SMD-free)
      was determined using the Sensory Responsiveness Questionnaire (SRQ). Sensory
      detection thresholds for skin warming, cooling, punctate dynamic tactile
      sensation, vibration and thermal pain thresholds for heat and cold stimuli were
      determined at several body sites. Pinprick pain and prickliness were also
      assessed, as well as the duration and intensity of the after-sensations of
      prickliness and pain evoked by the prickly stimuli. RESULTS: Compared to control
      adults, individuals with SMD showed significantly higher pain intensity to
      prickle stimuli, marginally higher pain intensity to pinprick and hypoesthesia to
      punctate dynamic tactile sensation at one of two sites tested. CONCLUSIONS: These
      results are in line with our previous study that investigated children with SMD
      using the same stimuli, and found similar results. We suggest a CNS involvement
      as the underlying mechanisms in SMD.

PMID- 22149535
TI  - Increased stability of S-nitrosothiol solutions via pH modulations.
AB  - S-nitrosothiol (RSNO) solutions represent a valuable source of nitric oxide and
      could be used as topical vasodilators, but their fast decomposition rate poses a
      serious obstacle to their potentially widespread therapeutic use. Our aim was to
      characterize and quantify the effect of pH on S-nitrosothiol formation and
      decomposition in simple aqueous solutions of S-nitrosoglutathione (GSNO), S
      nitroso-N-acetylcysteine (SNAC) and S-nitroso-3-mercaptopropionic acid (SN3MPA).
      Furthermore, we investigated the effect of storage pH on the stability of GSNO
      incorporated in poly(ethylene glycol)/ poly(vinyl alcohol) matrices. S
      nitrosothiol concentrations were measured spectrophotometrically and laser
      Doppler scanning method was used to assess dermal blood flow. GSH and NAC
      solutions reached a complete transformation to nitrosothiols when synthesized
      using acidic NaNO(2) solution. The initial concentration of all investigated
      RSNOs decreased more slowly with pH adjusted to mildly basic values (8.4-8.8) for
      the storage period. Polymer gels of PVA/PEG compositions at mildly basic storage
      pH further reduced the decomposition rate succeeding to contain 46.8% of the
      initial GSNO concentration for 25 days. This amount of topically administered
      GSNO was still capable of increasing the dermal blood flow over 200% in human
      subjects.

PMID- 22149536
TI  - Capture efficiency of Escherichia coli in fimbriae-mediated immunoimmobilization.
AB  - Capturing pathogens on a sensor surface is one of the most important steps in the
      design of a biosensor. The efficiency of a biosensor at capturing pathogens has
      direct bearing on its sensitivity. In this work we investigated the capturing of
      Escherichia coli on substrates modified with antibodies targeting different types
      of fimbriae: K88ab (F4), K88ac (F4), K99 (F5), 987P (F6), F41, and CFA/I. The
      results suggest that all these fimbriae can be used for the efficient
      immobilization of living E. coli cells. The immobilization efficiency was
      affected by the purity and clone type of the antibody and the fimbriae expression
      level of the bacteria. For a specific fimbriae type, a higher immobilization
      efficiency was often observed with the monoclonal antibodies.
      Immunoimmobilization was utilized in an antibody microarray immersed in a mixed
      culture of pathogens to demonstrate the rapid and simultaneous label-free
      detection of multiple pathogens within less than 1 h using a single test. The
      capture rate of living pathogens exceeds a single bacterium per 100 * 100 MUm(2)
      area per 0.5 h of incubation for a bulk concentration of 10(5) cfu/mL.

PMID- 22149537
TI  - Ploidy dimorphism and reproductive biology in Stenodrepanum bergii (Leguminosae),
      a rare South American endemism.
AB  - This is the first report on chromosome numbers and the reproductive behaviour in 
      Stenodrepanum  Harms, a rare endemic and monotypic legume genus from the arid and
      salty areas of central-western Argentina. Sixty individuals belonging to two
      populations from two salty areas ("salinas") were surveyed and included mostly
      triploid (2n = 3x = 36) and only two diploid (2n = 2x = 24) plants. Meiosis in
      diploids is regular, with bivalent pairing and uniform and viable pollen. In
      contrast, meiosis in triploids is characterized by high trivalent pairing, with
      irregularly shaped pollen and variation in cytoplasm content and stainability,
      which is in agreement with an unbalanced segregation occurring in anaphases I and
      II. However, different triploid plants/individuals showed various degrees of
      pollen fertility, which may be attributed to particular genotypes. Research on
      reproductive biology events indicates sexual cross-pollinated reproduction
      enhanced by protogyny in both cytotypes. All plants produced seeds, but seedlings
      were only recovered from diploid plants pollinated with triploids, and even those
      eventually perished. Chromosome counts in these seedlings revealed aneuploid
      chromosome numbers owing to the combination of unbalanced gametes.

PMID- 22149538
TI  - Characterization of fluorinated catansomes: a promising vector in drug-delivery.
AB  - Catansomes, which are vesicles prepared from mixtures of oppositely charged
      surfactants, have been suggested as effective alternatives to phospholipid
      vesicles, i.e., liposomes, in applications such as drug-delivery. This is mainly
      due to their enhanced chemical and physical stability as well as to their
      relatively easy preparation, which is an advantage for large-scale productions.
      In this study we have investigated catansomes prepared from a perfluorinated
      anionic surfactant (sodium perfluorooctanoate) premixed with a hydrogenated
      cationic surfactant (dodecyltrimethylammonium bromide or 1-dodecylpyridinium
      chloride). The aim was to gain insights into the physicochemical properties of
      these systems, such as size, stability, surface charge, and membrane morphology,
      which are essential for their use in drug-delivery applications. The catansomes
      were mostly unilamellar and 100-200 nm in size, and were stable for more than
      five months at room temperature. After loading the catansomes with the
      fluorescent marker calcein, they were found to exhibit an appreciable
      encapsulation efficiency and a low calcein leakage over time. The addition of
      fatty acids to calcein-loaded catansomes considerably promoted the release of
      calcein, and the rate and efficiency of calcein release were found to be
      proportional to the fatty acid concentration and chain length. Our results prove
      the feasibility of utilizing catansomes as drug-delivery vehicles as well as
      provide a means to efficiently release the encapsulated load.

PMID- 22149539
TI  - Telephone logs of neurosurgery specialty trainees: a time study.
AB  - PURPOSE: With a constant debate on working hours and improved patient outcomes,
      time studies are crucial to obtain and analyse timelines and work components.
      This includes time spent on communication. The aim of this study was to assess
      the magnitude and patterns of telephone call episodes in the work schedule of
      neurosurgery trainees. METHODS: Logs of handheld telephone sets assigned to
      neurosurgery specialty trainees in a British regional neurosurgical centre were
      obtained from the hospital switchboard for a 6-month period. This formed the
      primary data. Ringtime was added to the talktime for outgoing calls. Monday to
      Friday, 8 am-5 pm was considered as regular hours and the rest as other hours.
      The outcome measures used were number and duration of telephone episodes
      (individual and collective) and the timing of these episodes. RESULTS: During the
      study period of 6 months, there were 12071 incoming calls and 10712 outgoing
      calls (total calls-22783). The maximum number of incoming calls/ day/ trainee was
      in the range of 39-78 while the range for outgoing calls was 36-102. On an
      average, the on-call trainee made and received 33 and 36 calls respectively in a
      24-hour period (mean call duration was 1.7 minutes) which meant that a telephone
      call intruded into the schedule almost once every 21 minutes. Typically, the on
      call trainee spent 138 minutes on the telephone (69 calls) in 24 hours, while on
      an off-call day it was significantly less at 25 minutes (18 calls). Of the calls,
      67% happened out of regular hours. CONCLUSIONS: Time spent on the telephone is a
      significant work component and would have a bearing on timelines.

PMID- 22149540
TI  - Bidimensional techniques for stronger anterior torque control in extraction
      cases: a combined clinical and typodont study.
AB  - OBJECTIVE: To investigate the capacity of bidimensional techniques for torque
      control of anterior teeth in extraction cases. MATERIALS AND METHODS: Two
      different bidimensional techniques were distinguished by nomenclature as
      bidimensional-slot (bDS) and bidimensional-wire (bDW), respectively. (1) In the
      clinical study, patients were randomly assigned to three groups (ie, bDS [n  = 
      27], bDW [n  =  24], and control [n  =  25] groups). The major inclusion
      criterion was mild crowding in the upper arch, with the two upper first premolars
      (teeth 14 and 24) to be extracted. After space closure through standardized
      treatment, the torque of the upper central incisors (?TQ _U1) was calculated
      using the angle formed by the base of the U1 bracket and the working archwire on
      cephalograms. (2) In the typodont study, a standardized setup of the upper
      dentition with teeth 14 and 24 extracted was established. The spaces were closed
      through water bath followed by elastics, using the bDW or the conventional
      (control) technique, respectively. In six replicate experiments, after space
      closure, the ?TQ _U1 was measured on the standardized lateral photographs.
      RESULTS: (1) In the clinical study, after space closure, the ?TQ_U1 was 9.4
      degrees  +/- 3.4 degrees  (bDS), 8.3 degrees  +/- 3.3 degrees  (bDW), and 5.8
      degrees  +/- 2.9 degrees  (control), respectively. The ?TQ_U1 of bDS and bDW were
      both significantly (P < .05) larger than that of the control, but no statistical
      difference was found between them. (2) In the typodont study, after space
      closure, the ?TQ_U1 of bDW (8.5 degrees  +/- 0.9 degrees ) was significantly (P <
      .01) larger than that of the control (4.9 degrees  +/- 1.0 degrees ). CONCLUSION:
      The bDS and the bDW techniques may help enhance anterior torque control in
      extraction cases.

PMID- 22149541
TI  - Effects of maxillary molar distalization with Zygoma-Gear Appliance.
AB  - OBJECTIVE: To evaluate the dentoalveolar, skeletal, and soft tissue effects of
      the Zygoma-Gear Appliance (ZGA) when used for bilateral distalization of the
      maxillary molars. MATERIALS AND METHODS: The study group included 15 patients
      (mean age, 15.87 +/- 1.09 years; range: 14-18 years) treated with the ZGA system
      supported with zygomatic anchorage miniplates. The changes due to the
      distalization were evaluated from the lateral cephalometric films taken before
      and after distalization by means of a paired t-test. RESULTS: The mean treatment
      period required to achieve a Class I molar relationship was 5.21 months. The
      distalization amount of the maxillary molars was 4.37 +/- 2.15 mm (P < .001),
      and, thus, the rate for the distal movement of the molars was 0.84 mm per month.
      Maxillary first molars showed a slight intrusion (0.50 mm) (P > .05), while
      distal tipping was only 3.30 degrees  +/- 2.31 degrees  (P > .05). Furthermore,
      there was a decrease in overjet (-0.50 mm) (P > .05), indicating that there was
      no anchorage loss with use of the ZGA. CONCLUSIONS: Maxillary molar distalization
      without anchorage loss can be achieved in a short time with ZGA.

PMID- 22149542
TI  - Effects of screw and host factors on insertion torque and pullout strength.
AB  - OBJECTIVE: To experimentally study the effects of altering implant length, outer
      diameter, cortical bone thickness, and cortical bone density on the primary
      stability of orthodontic miniscrew implants (MSIs). MATERIALS AND METHODS:
      Maximum insertion torque (IT) and pullout strength (POS) of 216 MSIs were
      measured in synthetic bone with different cortical densities (0.64 g/cc or 0.55
      g/cc) and cortical thicknesses (1 mm or 2 mm). Three MSIs were evaluated: 6-mm
      long/1.75-mm outer diameter, 3-mm long/1.75-mm outer diameter, and 3-mm long/2.0
      mm outer diameter. To test POS, a vertical force was applied at the rate of 5
      mm/min until failure occurred. RESULTS: The 6-mm MSIs displayed significantly (P
      < .001) higher IT and POS than the 3-mm MSIs did. The 3-mm MSIs with 2.0-mm outer
      diameters showed significantly higher (P < .001) IT and POS than the 3-mm MSIs
      with 1.75-mm outer diameters. The IT and POS were significantly (P < .001)
      greater for the MSIs placed in thicker and denser cortical bone. CONCLUSION: Both
      outer diameter and length affect the stability of MSIs. Increases in cortical
      bone thickness and cortical bone density increase the primary stability of the
      MSIs.

PMID- 22149543
TI  - Treatment effects of quad-helix on the eruption pattern of maxillary second
      molars.
AB  - OBJECTIVE: To evaluate the effects of quad-helix treatment on the eruption
      pattern of maxillary second molars in patients with maxillary incisor crowding.
      MATERIALS AND METHODS: The lateral cephalograms of 40 consecutively treated
      patients in the early mixed-dentition group (treatment group) were examined in
      comparison with those of the same number of untreated patients with a similar
      form of malocclusion (control group). The cephalograms of the treated patients
      were taken at the start (T0) and at the end (T1) of treatment, and those of the
      untreated patients were also taken at about the same time as T0 and T1. The mean
      ages at T0 and T1 in the two groups were about the same. RESULTS: Distal tipping
      and movement and impeded extrusion of the maxillary first molars were notable in
      the treatment group compared with the control group. The actual treatment changes
      with the use of the quad-helix found expression in distal tipping and impeded
      vertical eruption of maxillary second molars. The more the maxillary first molars
      were tipped distally and the less the maxillary first molars extruded, the more
      the vertical eruption of the maxillary second molars was impeded. CONCLUSION:
      Quad-helix treatment gives rise to spontaneous distal tipping and impeded
      vertical eruption of the maxillary second molars.

PMID- 22149544
TI  - Biomechanical reevaluation of orthodontic asymmetric headgear.
AB  - OBJECTIVE: To investigate the distribution of distal and lateral forces produced
      by orthodontic asymmetric headgear (AHG) using mathematical models to assess
      periodontal ligament (PDL) influence and to attempt to resolve apparent
      inconsistencies in the literature. MATERIALS AND METHODS: Mechanical models for
      AHG were constructed to calculate AHG force magnitudes and direction using the
      theory of elasticity. The PDL was simulated by elastic springs attached to the
      inner-bow terminals of the AHG. The total storage energy (E(t)) of the AHG and
      the supporting springs was integrated to evaluate the distal and lateral forces
      produced by minimizing E(t) (Castigliano's theorem). All analytical solutions
      were derived symbolically. RESULTS: The spring-supported headgear model (SSHG)
      predicted the magnitude and distribution of distal forces consistent with our
      data and the published data of others. The SSHG model revealed that the lateral
      forces delivered to the inner-bow terminals were not equal, and the spring
      constant (stiffness of the PDL) affected the magnitude and direction of the
      resultant lateral forces. Changing the stiffness of the PDL produced a greater
      biomechanical effect than did altering the face-bow design. The PDL spring model
      appeared to help resolve inconsistencies in the literature between laboratory in
      vitro experiments and clinical in vivo studies. CONCLUSION: Force magnitude and
      direction of AHG were predicted precisely using the present model and may be
      applied to improve the design of AHG to minimize unwanted lateral tooth movement.

PMID- 22149545
TI  - Multidisciplinary approach to a traumatized unerupted dilacerated maxillary
      central incisor.
AB  - A patient with an impacted dilacerated maxillary left central incisor is
      presented. The 8-year-old girl also presented with protrusion of teeth and lips,
      posterior crossbite, anterior open bite, thumb-sucking habit, and transposition
      of the maxillary left lateral incisor and canine. The treatment consisted of a
      multidisciplinary approach, including surgery, orthodontics, endodontics, and
      prosthodontics. The dilacerated incisor was surgically exposed, tractioned,
      endodontically treated, and restored. Four premolars were extracted to correct
      the protrusion. The outcome was the accomplishment of a balanced and functional
      occlusion, resulting in a pleasant smile.

PMID- 22149546
TI  - Inflammatory markers in relation to nonalcoholic fatty liver disease in urban
      South Indians.
AB  - OBJECTIVE: This study assessed the association of inflammatory markers, high
      sensitivity C-reactive protein (hsCRP), and total leukocyte count with
      nonalcoholic fatty liver disease (NAFLD) in urban South Indians. SUBJECTS AND
      METHODS: We randomly selected subjects with and without NAFLD (n=100 each) from
      the Chennai Urban Rural Epidemiology Study conducted in Chennai in south India.
      NAFLD was diagnosed by ultrasonography. hsCRP was measured by nephelometry, and
      leukocyte count was measured by flow cytometry. Insulin resistance was analyzed
      by homeostasis assessment model using the following expression: fasting insulin
      (MUIU/mL)*fasting glucose (mmol/L)/22.5. RESULTS: Mean hsCRP values were
      significantly higher in subjects with NAFLD compared with those without (4.2+/
      1.2 mg/L vs. 2.2+/-0.4 mg/L; P<0.001). Leukocyte count was also higher in
      subjects with NAFLD compared with those without (7.8+/-1.4*10(3)/MUL vs 6.9+/
      0.9*10(3)/MUL, P<0.001). Both hsCRP (P<0.001) and leukocyte count (P<0.001)
      increased with increasing severity of NAFLD. Multiple logistic regression
      analysis was done using NAFLD as the dependent variable and hsCRP and leukocyte
      count as independent variables. Both hsCRP (odds ratio 1.293, 95% confidence
      interval 1.13-1.470, P<0.001) and leukocyte count (odds ratio 1.293, 95%
      confidence interval 1.069-1.564, P=0.008) had a significant association with
      NAFLD even after adjusting for waist circumference, insulin resistance, serum
      triglycerides, and presence of type 2 diabetes. CONCLUSIONS: hsCRP and leukocyte
      count are associated with NAFLD after adjusting for conventional cardiometabolic
      risk factors.

PMID- 22149547
TI  - Clinical utility of ImPACT assessment for postconcussion return-to-play
      counseling: psychometric issues.
AB  - Computerized neuropsychological testing is commonly utilized in the management of
      sport-related concussion. In particular, the Immediate Postconcussion Assessment
      and Cognitive Testing 2.0 program (ImPACT) is widely used to assess the cognitive
      functioning of athletes before and after a concussion. We review the evidence for
      the clinical utility of this program in terms of validity, reliability, and use
      in return-to-play decisions. We conclude that the empirical evidence does not
      support the use of ImPACT testing for determining the time of postconcussion
      return to play.

PMID- 22149548
TI  - Defining juvenile idiopathic arthritis remission and optimum time for disease
      modifying anti-rheumatic drug withdrawal: why we need a consensus.
AB  - Juvenile idiopathic arthritis (JIA) is an autoimmune disease of childhood
      requiring treatment with immune modulation therapy. It runs a relapsing and
      remitting course, with approximately half of affected children continuing with
      active disease into adult life. Defining clinical remission is challenging, but
      necessary, as it is critical in determining when potentially toxic therapy can be
      stopped. We found that preliminary consensus criteria for defining JIA remission
      are not being used in full by a representative sample of UK pediatric
      rheumatologists. Extending the period of remission, whilst on synthetic disease
      modifying anti-rheumatic drug (DMARD) medication, beyond 6 months does not seem
      to reduce the risk of relapse once medication is stopped. However, we found that
      most clinicians state that they still require at least 1 year in remission before
      DMARD withdrawal. There is increasing evidence that subclinical biomarkers may
      help to assess disease activity, and therefore aid clinicians in determining
      remission. In this review we argue that agreement on remission criteria and
      optimum timing of DMARD withdrawal is crucial for consistent clinical practice,
      and further research in this area is needed.

PMID- 22149549
TI  - Anesthetic-related neurotoxicity and the developing brain: shall we change
      practice?
AB  - Millions of human infants receive general anesthetics for surgery or diagnostic
      procedures every year worldwide, and there is a growing inquietude regarding the
      safety of these drugs for the developing brain. In fact, accumulating
      experimental evidence together with recent epidemiologic observations suggest
      that general anesthetics might exert undesirable effects on the immature nervous
      system. The goal of this review is to highlight basic science issues as well as
      to critically present experimental data and clinical observations relevant to
      this possibility. By acting on a plethora of ligand-gated ion channels, general
      anesthetics are powerful modulators of neural activity. Since even brief
      interference with physiologic activity patterns during critical periods of
      development are known to induce permanent alterations in brain circuitry,
      anesthetic-induced interference with brain development is highly plausible. In
      line with this hypothesis, compelling experimental evidence, from rodents to
      primates, suggests increased neuroapoptosis and associated long-term
      neurocognitive deficits following administration of these drugs at defined stages
      of development. Recent epidemiologic studies also indicate a potential
      association between anesthesia/surgery and subsequently impaired neurocognitive
      function in humans. It is, however, important to note that extrapolation of
      experimental studies to human practice requires extreme caution, and that
      currently available human data are hindered by a large number of potentially
      confounding factors. Thus, despite significant advances in the field, there is
      still insufficient evidence to determine whether anesthetics are harmful to the
      developing human brain. Consequently, no change in clinical practice can be
      recommended.

PMID- 22149551
TI  - Candesartan cilexetil in children and adolescents aged 1 to <17 years with
      hypertension: profile report.

PMID- 22149550
TI  - Celiac disease in pediatric patients with autoimmune hepatitis: etiology,
      diagnosis, and management.
AB  - Celiac disease (CD) is defined as a permanent intolerance to ingested wheat
      gliadins and other cereal prolamins, occurring in genetically susceptible people.
      Persistent elevation of serum aminotransferase activity is expression of liver
      damage related to CD, which occurs in two distinctive forms. The most frequent is
      a mild asymptomatic liver injury, with a moderate increase of serum
      aminotransferase activities and a mild inflammatory portal and lobular infiltrate
      on liver biopsy (celiac hepatitis), reversible on a gluten-free diet (GFD). More
      rarely, severe and progressive inflammatory liver damage, induced by an
      autoimmune process and identified as autoimmune hepatitis (AIH), can develop and
      it is generally unaffected by gluten withdrawal. Surveys that included only
      pediatric patients report a wide range of prevalence of CD in AIH of 11.5-46%
      (mean 21.5%). CD and AIH share selected combinations of genes coding for class II
      human leukocyte antigens, which could explain their coexistence. Increased
      intestinal permeability and circulation of anti-tissue transglutaminase (tTG)
      have also been considered as further potential causes of liver damage in CD
      patients. tTG in the liver and in other extraintestinal tissues could modify
      other external- or self-antigens and generate different neo-antigens, which are
      responsible for liver injury in patients with CD. Patients with AIH represent a
      population at high risk for developing CD; screening for CD should be integrated
      into the diagnostic routine of all patients with AIH, with or without
      gastrointestinal manifestations, before starting immunosuppressive treatments.
      The only currently available treatment for CD is the GFD and the supportive
      nutritional care for iron, calcium, and vitamin deficiencies. Due to the
      difficulties of a GFD, in the past decade researchers have become increasingly
      interested in therapeutic alternatives to continuous or intermittent use of a GFD
      in patients with CD. Interventions addressed to correct the defect in the
      intestinal barrier are currently at the most advanced stage of clinical trials.
      The impact of a GFD on the outcome of AIH is not clear but it seems to be
      ineffective in the treatment of AIH. The early detection and treatment of CD,
      however, may prevent progression to end-stage liver failure.

PMID- 22149552
TI  - Meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine
      (Menveo((r))): profile report.

PMID- 22149553
TI  - Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) [Prevenar
      13((r))]: profile report.

PMID- 22149554
TI  - A comparison of preservative-free diclofenac and preserved diclofenac eye drops
      after cataract surgery in patients with diabetic retinopathy.
AB  - PURPOSE: The aim of this study was to compare the anti-inflammatory efficacy of
      preservative-free and preserved 0.1% diclofenac eye drops for the management of
      postoperative inflammation after cataract surgery in patients with
      nonproliferative diabetic retinopathy and in normal controls. METHODS: Forty-two
      diabetic patients and 50 normal control patients who underwent small-incision
      phacoemulsification cataract surgery bilaterally received topical preservative
      free diclofenac in 1 eye and preserved diclofenac in the other eye. The corrected
      distance visual acuity (CDVA) as determined by a logarithm of the minimum angle
      of resolution (logMAR) chart, intraocular pressure (IOP), foveal thickness (FT)
      using optical coherence tomography (OCT), and the anterior chamber flare (ACF)
      score measured with a laser flare cell meter were monitored for 12 weeks after
      surgery. RESULTS: In the eyes with diabetic retinopathy, there were no
      significant differences in CDVA, IOP, FT, and ACF score between the right and
      left eyes at the initial exam. After cataract surgery, changes in CDVA, IOP, and
      FT were not influenced by the preservative in the diclofenac eye drops. In
      contrast, the ACF score in the eyes treated with preserved diclofenac showed
      slower recovery from postoperative inflammation than the eyes treated with
      preservative-free diclofenac. In the normal control eyes, similar but milder
      changes were observed in each of the clinical parameters. CONCLUSIONS: Because
      preservative suppressed the anti-inflammatory efficacy of topical diclofenac
      after cataract surgery, preservative-free diclofenac may have an improved safety
      profile during postoperative treatment, especially in patients with diabetic
      retinopathy.

PMID- 22149556
TI  - Oxidative stress and acute pancreatitis.

PMID- 22149555
TI  - Efficacy of a phosphorodiamidate morpholino oligomer antisense compound in the
      inhibition of corneal transplant rejection in a rat cornea transplant model.
AB  - PURPOSE: The cornea is one of the most commonly transplanted tissues. The
      morpholino-oligomer antisense compound AVI-5126 suppresses expression of proto
      oncogene c-myc, a key factor in transplant rejection. AVI-5126 was evaluated in a
      rat cornea transplant model. METHODS: Donor corneas obtained from August x
      Copenhagen Irish rats were stored in OptisolTM containing 1.0 or 0.5 mg/mL AVI
      5126 or Optisol alone for 24 h before transplant. Recipient Lewis rats were
      treated topically 3x/d with TobraDexTM and with 1.0 or 0.5 mg/mL of AVI-5126 or
      saline with daily monitoring for rejection using a modified McDonald-Shadduck
      Slit Lamp Scale. Using the high-performance liquid chromatography technique, the
      stability of AVI-5126 (0.5 mg/mL) in Optisol was evaluated for 30 days. AVI-5126
      corneal transport was measured using Ussing chamber mounted rabbit corneas. The
      potential ocular toxicity of AVI-5126 (0.5 mg/mL) was evaluated after 8 days of
      3x/d topical application in rats and in-vitro by incubation of human corneas for
      8 days. RESULTS: Cornea storage in Optisol containing 1.0 mg/mL AVI-5126 plus
      post-transplant topical tid AVI-5126 (1.0 mg/mL) application significantly
      increased graft survival (7.0+/-1.6 days) versus 5.0+/-0.8 days for Optisol alone
      storage plus post-transplant topical tid saline application (P<0.001). After 30
      days of storage, no significant degradation of AVI-5126 in Optisol was noted by
      high-performance liquid chromatography analysis. After 24 h, 5 MUg/mL (1% of
      total dose) crossed the corneas mounted in Ussing chambers. Neither extended
      topical application of AVI-5126 to rats nor incubation of human corneas in AVI
      5126 decreased endothelial cell density. CONCLUSIONS: Graft rejection was
      significantly delayed after pretransplantation storage of graft corneas in
      Optisol containing AVI-5126 followed by topical application of AVI-5126 post
      transplantation. AVI-5126 was well tolerated, stable, and effectively penetrated
      the cornea.

PMID- 22149557
TI  - Malondialdehyde in early phase of acute pancreatitis.
AB  - AIMS: to assess oxidative stress in acute pancreatitis, its evolution over time
      and its relationship with the severity of the disease. METHODS: during a two-year
      period, patients with acute pancreatitis with less than 24 hours of pain were
      evaluated. Serum was obtained the first, second and fourth day from admittance,
      if complications were detected, and after recovery. Malondialdehyde was
      determined by high performance liquid chromatography. Twenty healthy volunteers
      constituted the control group. Malondialdehyde between groups was compared with
      Mann-Whitney and Kruskal-Wallis tests; malondialdehyde evolution was studied with
      Wilcoxon test. RESULTS: one hundred and sixty-nine patients were included (91
      women, median age 67 years, range 20-95); 33 suffered a severe episode.
      Malondialdehyde decreased from first to fourth day (0.600 vs. 0.451 vs. 0.343 M,
      respectively, p < 0.05). When complications were detected, malondialdehyde level
      was similar to that of first and second day (0.473 M, p > 0.05). In severe
      attacks malondialdehyde was higher than in control group at day 2 (severe: 0.514;
      mild: 0.440; control: 0.347 M, p < 0.05 severe vs. control). CONCLUSIONS: an
      early oxidative stress is observed in acute pancreatitis. In severe attacks,
      oxidative stress remains high longer than in mild episodes. The onset of
      complications is associated with high malondialdehyde concentration.

PMID- 22149558
TI  - The burden and management of patients with IBS: Results from a survey in spanish
      gastroenterologists.
AB  - BACKGROUNDS: irritable bowel syndrome (IBS) is a common and complex disorder.
      Though it is estimated that IBS constitutes an important part of the
      gastroenterology (GI) practice, the burden of this problem in the GI outpatients
      clinics in Spain is unclear. AIM: the aim of this study is to obtain a "shot" of
      the burden and management of this syndrome in the daily GI practice. METHODS: 508
      general gastroenterologists from all over the country were approached and asked
      to complete a survey that included questions about their daily practice and the
      definition, diagnosis and treatment of IBS. RESULTS: 55% of the surveyed
      physicians estimate that IBS constitute between a quarter and a half of all their
      consultations; and pointed out that most of these patients were referred from
      primary care. Overall, the Spanish gastroenterologists show an adequate knowledge
      of the different diagnostic criteria, though they do not always follow the
      current guidelines. Up to 55% of the physicians always perform a complementary
      test to support their diagnosis and 40% order a diagnostic test only in older
      patients (> 50 years) or in presence of alarm symptoms. Interestingly, 80% of the
      gastroenterologists start empirical treatment based on the patients' symptoms.
      CONCLUSIONS: though Spanish gastroenterologists seem to have an adequate
      theoretical knowledge of the disease, they do not systematically follow current
      guidelines and tend to manage IBS symptoms based on their own criteria.

PMID- 22149559
TI  - Argon plasma coagulation and hyperbaric oxygen therapy in chronic radiation
      proctopathy, effectiveness and impact on tissue toxicity.
AB  - BACKGROUND: chronic radiation proctopathy (CRP) is associated with recurrent
      rectal bleeding and transfusional requirements. Argon plasma coagulation (APC)
      and hyperbaric oxygen therapy (HOT) have been shown to be effective in the
      control of CRP. No prospective comparisons have been reported between these
      treatments. AIM: the aim was to evaluate the effectiveness, safety and impact on
      tissue toxicity of APC compared to HOT in patients with CRP. MATERIAL AND
      METHODS: a prospective study for evaluating treatment response was conducted.
      Patients with cervical cancer and CRP with rectal bleeding were recruited. They
      had not received previous treatment. Collected data included: demographics,
      previous radiation dosage, duration and severity of rectal bleeding. Hemoglobin,
      transfusional requirements, and tissue toxicity (SOMA LENT questionnaire) at
      baseline and at 1, 2, and 3 months follow up were recorded. RESULTS: thirty-one
      patients were included, 14 in the APC group and 17 in the HOT group. No response
      was noted in 13 and 18% of patients in the APC and HOT group respectively (p =
      NS). At the 1 and 2 months follow-up, the APC group showed a significantly better
      response in terms of transfusional requirements (0.6 vs. 3.4 and 0.7 vs. 2.5) and
      tissue toxicity score (5.3 vs. 8.6 and 3.8 vs. 7.248). After 3 months, both
      groups showed further improvement in all parameters without significant
      differences between them. CONCLUSIONS: APC and HOT were effective, safe and
      decreased the tissue toxicity scores in patients with CRP. However, response rate
      was higher and faster in the APC group.

PMID- 22149560
TI  - Appendicular pseudodiverticula and acute appendicitis. Our 12-year experience.
AB  - INTRODUCTION: the presence of diverticula and their complications in the cecal
      appendix is an uncommon disease. We present a series of 13 patients with this
      condition, and perform a review of the literature. PATIENTS AND METHOD: we
      carried out a retrospective study of patients undergoing appendectomy for acute
      appendicitis in the last twelve years in our department. The pathological
      examination of these episodes revealed 13 cases with a diagnosis of diverticular
      disease, all of them consisting of pseudodiverticula. Their clinical
      manifestations, laboratory results, imaging tests, and histology were analyzed,
      and findings were compared to those in the previous literature. RESULTS: the
      incidence of diverticular disease in our setting was 13 cases (0.8%) among 1634
      appendectomies for acute appendicitis. Diverticulitis was found in 8 patients
      (61.5%), and diverticulosis (38.5%) in 5. Appendicular perforation was more
      common in patients with diverticular disease (53.8%) as compared to those without
      this condition (31.1%). CONCLUSIONS: complicated diverticular disease in the
      vermiform appendix of adult patients may result in insidious, recurrent
      manifestations that may confound preoperative diagnosis. A higher risk for
      appendicular perforation renders appendectomy the therapy of choice, even
      prophylactically when the condition is incidentally identified preoperatively.

PMID- 22149561
TI  - New clinical and toxicological scenario of gammaglutamyltranspeptidase.
AB  - After the discovery of gammaglutamyltranspeptidase in 1950 by Hanes, the
      significance of its increased levels in clinical practice has mainly been focused
      on ethanol toxicity, and also some neoplasms and biliary tract obstruction. More
      recently, attention has swift to the metabolic functions of this enzyme, as a
      neutralizer of oxygen free radicals and as a glutathione donor to the cell. High
      serum levels of gammaglutamyltranspeptidase is known to occur when oxidative
      stress is increased, or associated with several vascular risk factors and the
      insulin resistance syndrome, as an early marker of diabetes. There are also a
      number of drugs that induce the expression of the tissue enzyme (microsomes) with
      the result of high serum levels without structural damage to the liver. Because
      it is a ubiquitous enzyme, a very high number of causes can be involved, that may
      be difficult to recognize. Finally, because glutathione is necessary to conjugate
      a number of chemical compounds, from an epidemiological and toxicological
      perspective, the enzyme might be useful as a biomarker of several ambient
      toxins.In this review we want to emphasize the increasing clinical and diagnostic
      significance of this enzyme discovered half a century ago.

PMID- 22149562
TI  - Nodular colonic lesion in a nephrectomized patient.

PMID- 22149563
TI  - Ascaris lumbricoides as etiologic factor for pancreas inflammatory tumor.

PMID- 22149564
TI  - Wernicke's encephalopathy after cephalic pancreaticoduodenectomy.
AB  - Wernicke's encephalopathy is an acute neurological disorder resulting from
      thiamine deficiency. We report a case in a young patient who underwent a cephalic
      duodenopancreatectomy with a bleeding duodenal ulcer refractory to endoscopic and
      surgical treatment, requiring total parenteral nutrition, without thiamine
      supplementation.

PMID- 22149565
TI  - [Acute Alcoholic Hepatitis].

PMID- 22149566
TI  - Not only condyloma acuminata of the anal canal: a rare case with coexisting
      adenocarcinoma.

PMID- 22149567
TI  - Refractory ulcerative chronic pouchitis in a patient with Gardner syndrome
      following restorative proctocolectomy with ileal pouch-anal anastomosis.

PMID- 22149568
TI  - Colocolonic intussusception secondary to high grade colonic leiomysarcoma.

PMID- 22149569
TI  - Endoscopic ultrasound guided fistulization between left intrahepatic duct and
      jejunum in a patient with Roux-en-Y anastomosis and jaundice.

PMID- 22149570
TI  - Rectal bleeding in a young woman.

PMID- 22149571
TI  - Porto-mesenteric thrombosis of congenital origin: an infrequent cause of acute
      abdomen.

PMID- 22149572
TI  - Cumyl ester as the C-terminal protecting group in the enantioselective alkylation
      of glycine benzophenone imine.
AB  - Cumyl ester is an optimal C-terminal protecting group for glycine benzophenone
      imine in asymmetric alkylation reactions catalyzed by Cinchona chiral phase
      transfer catalysts. High levels of enantioselectivity have been obtained (up to
      94% ee) with this substrate, which provides an attractive alternative to the
      analogous tert-butyl ester. N-terminal imines and the C-terminal esters can be
      cleaved from alkylation products by hydrogenolysis, while maintaining acid-labile
      side chain protecting groups.

PMID- 22149573
TI  - Medical therapy for nonalcoholic fatty liver disease in children and adolescents.

PMID- 22149574
TI  - The role of endoscopy in the management of autoimmune pancreatitis.

PMID- 22149576
TI  - Clarification of trial end points presented in a recent review of linaclotide.

PMID- 22149578
TI  - Crofelemer for the treatment of secretory diarrhea.
AB  - Secretory diarrhea is a leading cause of morbidity and mortality worldwide.
      Crofelemer is a first-in-class antidiarrheal agent that simultaneously targets
      two distinct channels, the cystic fibrosis conductance regulator and calcium
      activated chloride channel, responsible for chloride and fluid secretion in the
      GI tract. Crofelemer is a novel compound extracted from the stem bark latex of
      the Croton lechleri tree found in the western Amazonian region of South America.
      There is little to no systemic absorption of crofelemer when given orally and
      studies have shown minimal toxicity beyond mild gastrointestinal effects. In
      studies in diarrheal illness associated with primarily a secretory component,
      such as cholera, travelers' diarrhea and acute infectious diarrhea, crofelemer
      has shown improvements in stool consistency and duration of symptoms. Less clear,
      but interesting, results have been observed in other diarrheal diseases
      associated with a mixed pathology, including diarrhea in patients with HIV and
      diarrhea-predominant irritable bowel syndrome.

PMID- 22149579
TI  - HZT-501 (DUEXIS((r)); ibuprofen 800 mg/famotidine 26.6 mg) gastrointestinal
      protection in the treatment of the signs and symptoms of rheumatoid arthritis and
      osteoarthritis.
AB  - Arthritis affects nearly 50 million people in the USA and, with the aging of the
      population, the prevalence is expected to rise. While NSAIDs are very effective
      in relieving pain associated with osteoarthritis (OA) and rheumatoid arthritis
      (RA), they are associated with side effects, including gastrointestinal (GI)
      toxicity, which may manifest as dyspepsia, ulcers and/or bleeding. A number of
      approaches have been employed in an effort to either completely avoid or reduce
      the risk of GI toxicities associated with NSAID use. Two new products combining
      an NSAID with a gastroprotective agent have recently been approved and other
      agents are in the pipeline. Patient adherence to prescribed gastroprotective
      therapy is known to be poor, often resulting in an increased risk of GI events in
      patients taking NSAIDs. These newer combination products may fulfill an important
      need for many patients who need to receive NSAIDs for the pain of OA and RA, but
      who are also at risk of upper GI events. This article reviews preclinical and
      clinical results for a new fixed-dose combination of ibuprofen and famotidine,
      DUEXIS((r)) (HZT-501), which has recently been approved in the USA for the relief
      of signs and symptoms of RA and OA and to decrease the risk of developing upper
      GI ulcers.

PMID- 22149580
TI  - Angle-resolved low-coherence interferometry: an optical biopsy technique for
      clinical detection of dysplasia in Barrett's esophagus.
AB  - Angle-resolved low-coherence interferometry (a/LCI) is an optical biopsy
      technique that measures scattered light from tissue to determine nuclear size
      with submicron-level accuracy. The a/LCI probe can be deployed through the
      accessory channel of a standard endoscope and provides feedback to physicians to
      guide physical biopsies. The technique has been validated in animal and ex vivo
      human studies, and has been used to detect dysplasia in Barrett's esophagus
      patients in vivo. In a recent clinical study of 46 Barrett's esophagus patients,
      a/LCI was able to detect dysplasia with 100% sensitivity and 84% specificity.
      This report reviews the technique and discusses its potential clinical utility.

PMID- 22149581
TI  - Gluten sensitivity: problems of an emerging condition separate from celiac
      disease.
AB  - Gluten sensitivity appears to be emerging as a separate condition from celiac
      disease, yet no clear definition or diagnosis exists. As a result, patients with
      gluten sensitivity experience delayed diagnosis and continuing symptoms if they
      consume gluten. This emerging medical problem may involve human genetics, plant
      genetic modifications, gluten as a food additive, environmental toxins, hormonal
      influences, intestinal infections and autoimmune diseases. The treatment is
      similar to that for celiac disease - a gluten-free diet. The use of a gluten-free
      diet or an elimination diet is encouraged in assisting people to determine
      whether or not they are gluten sensitive. It is time to not only recognize, but
      to treat and further research gluten sensitivity, as unconfirmed environmental
      factors continue to spread this problem further into the general population.

PMID- 22149582
TI  - QT interval prolongation in liver cirrhosis: innocent bystander or serious
      threat?
AB  - The ECG QT interval measures the length of ventricular systole. Its prolongation
      is essentially caused by a delayed repolarization phase, and is associated with
      an increased risk of ventricular arrhythmias and sudden death in several
      congenital and acquired conditions. Abnormalities in cardiac electrophysiology
      are well documented in patients with liver cirrhosis, and the prolonged QT
      interval has emerged as the electrophysiological hallmark of cirrhotic
      cardiomyopathy. This article will focus on: first, the epidemiology of QT
      interval prolongation in cirrhosis; second, the potential molecular mechanisms
      responsible for the pathogenesis of this electrophysiological abnormality and the
      putative role of circulating cardiotoxins; third, its prognostic meaning; and
      fourth, its clinical relevance, in terms of the association between the presence
      of a long QT interval and the occurrence of ventricular arrhythmias in cirrhotic
      patients treated with drugs known to increase the QT length or exposed to
      stressful conditions, such as liver transplantation, gastrointestinal bleeding
      and shock.

PMID- 22149583
TI  - Update on hepatic stellate cells: pathogenic role in liver fibrosis and novel
      isolation techniques.
AB  - Hepatic stellate cells (HSCs), also called Ito cells or lipocytes, are vitamin A
      storing cells located in the Disse space between hepatocytes and sinusoidal
      endothelial cells. Upon liver injury, these cells transdifferentiate into
      extracellular matrix-producing, highly proliferative myofibroblasts that promote
      hepatic fibrogenesis. Other possible collagen-producing cells in liver fibrosis
      include portal fibroblasts, bone marrow-derived cells (mesenchymal stem cells,
      fibrocytes and hematopoietic cells) and parenchymal cells undergoing epithelial
      to-mesenchymal transition. Important factors and signaling pathways for HSC
      activation, as well as different functions of HSC during homeostasis and
      fibrosis, such as collagen production, secretion of cytokines and chemokines,
      immune modulation and changes in contractile features, as well as vitamin A
      storage capacity, have been identified in vitro and in vivo. Novel isolation
      techniques, specifically HSC sorting by FACS via autofluorescence and antibodies,
      will provide us with further opportunities to advance our understanding of HSC
      biology in health and disease.

PMID- 22149584
TI  - Microbes, intestinal inflammation and probiotics.
AB  - Inflammatory bowel disease (IBD) is known for causing disturbed homeostatic
      balance among the intestinal immune compartment, epithelium and microbiota. Owing
      to the emergence of IBD as a major cause of morbidity and mortality, great
      efforts have been put into understanding the sequence of intestinal inflammatory
      events. Intestinal macrophages and dendritic cells act in a synergistic fashion
      with intestinal epithelial cells and microbiota to initiate the triad that
      governs the intestinal immune responses (whether inflammatory or regulatory). In
      this review, we will discuss the interplay of intestinal epithelial cells,
      bacteria and the innate immune component. Moreover, whether or not genetic
      intervention of probiotic bacteria is a valid approach for attenuating/mitigating
      exaggerated inflammation and IBD will also be discussed.

PMID- 22149585
TI  - Pancreatic cancer: an endoscopic perspective.
AB  - Pancreatic cancer continues to be a diagnostic and therapeutic challenge. The
      advent of endoscopic ultrasound-guided interventions have brought about a
      paradigm shift in the endoscopic approach to diagnosis, treatment and palliation
      of this common malignancy. The last decade has witnessed significant advances in
      techniques of endoscopic biliary drainage, endoluminal stenting, celiac plexus
      neurolysis and image-guided radiation therapy, which have transformed the scope
      of palliation in pancreatic cancer. Moreover, endoscopic ultrasound-aided
      intratumoral delivery of fiducials, radioisotopes and chemotherapeutic agents
      have shown promising results and warrant further investigation. This review
      summarizes the recent advances in endoscopic applications for the management of
      pancreatic neoplasms.

PMID- 22149586
TI  - Self-expandable metal stents in malignant biliary obstruction.
AB  - Malignant biliary obstruction can be due to direct tumor infiltration, extrinsic
      compression, adjacent inflammation, desmoplastic reaction from tumors or, more
      commonly, a combination of the above factors. Pancreatic cancer is the most
      common cause of malignant biliary obstruction, and jaundice occurs in 70-90% of
      the patients during the course of the disease. Compared with the uncovered metal
      stents, covered metal stents have longer patency and a lower rate of tumor
      ingrowth, but have a higher rate of stent migration. To combat the occlusion and
      provide an antitumor effect, drug-eluting stents were developed. A duodenal
      stricture complicates biliary stent placement in 10-20% of patients with distal
      biliary obstruction due to pancreatic cancer. When both strictures are
      considered, a biliary stent can be placed either preceding or following duodenal
      stent placement. Complications of self-expandable metal stents include stent
      occlusion, stent migration, cholecystitis and pancreatitis.

PMID- 22149587
TI  - Quality of life after esophagectomy for cancer.
AB  - Esophageal cancer is an aggressive and physically and emotionally devastating
      disease. It has one of the poorest survival rates among all malignant tumors,
      mainly due to late symptom presentation and early metastatic dissemination. Cure
      is possible through extensive surgery, typically followed by a long recovery
      period, affecting general well-being, as well as basic aspects of life, such as
      eating, drinking and socializing. Health-related quality of life (HRQL) is a
      multidimensional concept assessing symptoms and functions related to a disease or
      its treatment from the patient's perspective. HRQL is a fundamental part of
      treatment in surgical oncology, particularly in esophageal cancer. This review
      assesses the scientific data regarding some HRQL aspects after esophageal cancer
      surgery, for example, postoperative recovery time, determinants of postoperative
      HRQL and long-term HRQL.

PMID- 22149590
TI  - Automated module radiolabeling of peptides and antibodies with gallium-68,
      lutetium-177 and iodine-131.
AB  - Our objectives were to automate radiolabeling of therapeutic activities for safe,
      reliable, cost-effective, practical routine preparation of (177)Lu-radiopeptides,
      (131)I radioimmunotherapeutic agents, and (68)Ga-peptide PET diagnostics and, in
      particular, minimize radiation exposure to the radiopharmaceutical chemist.
      Reprogramming and adaptation of a commercially available synthetic module (IBA
      molecular; Synthera(r)) allowed high yield, fully automated, in-house
      radiolabeling of novel therapeutic and diagnostic radiopharmaceuticals under
      remote shielded sterile conditions. Radiochemical yield and purity was measured
      by instant thin-layer chromatography and high-performance liquid chromatography.
      (68)Ga-octreotate and (177)Lu-octreotate were synthesized, resulting in both
      radiochemical yield and radiochemical purity greater than 99%. Synthesis of
      (131)I-rituximab resulted in a yield of 60%, with a radiochemical purity greater
      than 99%. Using 400 MBq (68)GaCl(3) per synthesis, the estimated absorbed body
      and hand dose for a manual synthesis was 2 and 27 MU Sv, contrasting with
      automated synthesis exposure of 1.3 and 7.9 MU Sv. Using 8000 MBq (177)LuCl(3)
      per synthesis, the estimated absorbed body and hand dose for a manual synthesis
      was 44.7 and 75 MU Sv, contrasting with automated synthesis exposure of 2.5 and
      20 MU Sv. Using 6000 MBq (131)I per synthesis, the estimated absorbed body and
      hand dose for a manual synthesis was 83.7 and 335 MU Sv, contrasting with
      automated synthesis exposure of 10.9 and 54.7 MU Sv. The reduction in radiation
      exposure by automated synthesis of radiopharmaceuticals in the Synthera(r) module
      was at least five fold. Automated synthesis of therapeutic (177)Lu and (131)I
      radiopharmaceuticals and (68)Ga PET agents in the shielded sterile Synthera(r)
      module is simple, practical, and efficient and virtually eliminates radiation
      exposure to the radiopharmaceutical chemist.

PMID- 22149589
TI  - Dextran-conjugated vascular endothelial growth factor receptor antibody for in
      vivo melanoma xenografted mouse imaging.
AB  - Intact immunoglobulin G antibody has a relatively large molecule size of
      approximately 150 kDa that remains in the bloodstream for many weeks, which is a
      considerable disadvantage when it is used to carry radioactive materials for
      imaging. To lower background activity and increase the contrast of images, we
      investigated antivascular endothelial growth factor (VEGF) receptor 2 antibody
      (DC101) conjugated dextran for VEGF receptor 2 imaging in tumor xenografted mice.
      DTPA-conjugated aminodextran was synthesized, reacted with sulfo-LC-SPDP, and
      then reacted with DC101. The binding affinity of DTPA-dextran-DC101 to Flk-1 was
      measured. The gamma imaging and biodistributions of (99m)Tc-DTPA-dextran-DC101,
      (99m)Tc-DTPA-DC101, and (125)I-DC101 were studied in B16F10 melanoma xenografted
      mice. The dissociation values for DC101, DTPA-DC101, and DTPA-dextran-DC101 were
      22.48, 3.05, and 14.74 pM, respectively. In gamma images, (99m)Tc-DTPA-dextran
      DC101 showed weak liver uptake and rapid kidney elimination. In biodistribution
      results, the liver uptake of (99m)Tc-DTPA-dextran-DC101 was similar with that of
      (99m)Tc-DTPA-DC101 at each time point. However, the blood activity of (99m)Tc
      DTPA-dextran-DC101 has shown significant differences, compared with (99m)Tc-DTPA
      DC101 at all time points. The tumor accumulation of dextran-conjugated antibody
      was increased with time, whereas that of dextran nonconjugated antibody
      decreased. In particular, the pattern of tumor uptake of (99m)Tc-DTPA-dextran
      DC101 was similar to that of (125)I-DC101, so this was thought to reflect the
      kinetics of DC101, unlike the nonconjugated form. The results of this study
      suggested that introduction of dextran moiety to make (99m)Tc-radiolabeled DC101
      imaging agent could provide better images with the impaired background and the
      steady increasing binding to the receptor. However, further studies are necessary
      to improve clinical pharmacokinetics, such as enhancement of tumor uptake and
      impaired renal uptake.

PMID- 22149591
TI  - Parallel kinetic resolution of acyclic gamma-amino-alpha,beta-unsaturated esters:
      application to the asymmetric synthesis of 4-aminopyrrolidin-2-ones.
AB  - Conjugate addition of a 50:50 pseudoenantiomeric mixture of lithium (R)-N-benzyl
      N-(alpha-methylbenzyl)amide and lithium (S)-N-3,4-dimethoxybenzyl-N-(alpha
      methylbenzyl)amide to a range of racemic acyclic gamma-amino-alpha,beta
      unsaturated esters (derived from the corresponding alpha-amino acids) effects
      their efficient parallel kinetic resolution, allowing the preparation of
      enantiopure beta,gamma-diamino esters. The beta,gamma-diamino ester products of
      these reactions are readily converted into the corresponding substituted 4
      aminopyrrolidin-2-ones via N-debenzylation and cyclization.

PMID- 22149599
TI  - Enhanced growth of lactobacilli and bioconversion of isoflavones in biotin
      supplemented soymilk by electroporation.
AB  - This study aimed at utilizing electroporation to further enhance the growth of
      lactobacilli and their isoflavone bioconversion activities in biotin-supplemented
      soymilk. Strains of lactobacilli were treated with different pulsed electric
      field strength (2.5, 5.0 and 7.5 kV/cm) for 3, 3.5 and 4 ms prior to inoculation
      and fermentation in biotin-soymilk at 37 degrees C for 24 h. Electroporation
      triggered structural changes within the cellular membrane of lactobacilli that
      caused lipid peroxidation (p < 0.05) and alteration of membrane fluidity (p <
      0.05). This was due to the application of electric potential difference across
      membrane that induced pores formation and subsequently increased membrane
      permeability. Reversible permeabilized cells resumed growth to >9 log CFU/ml
      after fermentation in biotin-soymilk (p < 0.05). Lactobacilli cells treated at
      electric field strength of 7.5 kV/cm for 3.5 ms also showed enhanced beta
      glucosidase activity (p < 0.05) compared to lower doses and control, leading to
      increased bioconversion of isoflavones glucosides to aglycones in biotin-soymilk
      (p < 0.05). Results from this study show that electroporation could be used to
      produce biotin-soymilk with increased bioactive aglycones.

PMID- 22149600
TI  - Development of a minimum protocol for assessment in the paediatric voice clinic.
      Part 2: subjective measurement of symptoms of voice disorder.
AB  - The European Laryngological Society (ELS) recommend that functional assessment of
      voice disorder in adults requires evaluation of a number of different parameters.
      These include perceptual evaluation of voice, videostroboscopic imaging of vocal
      fold movement, acoustic analysis of specific voicing aspects, aerodynamic support
      for voicing, and a subjective rating of voice impact. No specific guidelines are
      available for children, but a similar range of parameters is needed to guide
      intervention and measure outcomes. The development of subjective voice measures
      for adults and their adaptations for the paediatric population are reviewed and
      compared to the research comparing these to evaluation of vocal function. The
      need for further refinement of child assessment measures, and a proposal of how
      these might be developed, is discussed.

PMID- 22149605
TI  - Binary interactions and salt-induced coalescence of spherical micelles of
      cationic surfactants from molecular dynamics simulations.
AB  - A direct estimation of salt-mediated potential of mean force (PMF) between
      spherical micelles of cationic surfactants is obtained for the first time using
      molecular dynamics (MD) simulations. Coarse-grained (CG) potentials benchmarked
      in an earlier study [Langmuir, 2011, 27(11), 6628-6638] are used to model a
      binary system of cetyltrimethylammonium chloride (CTAC) surfactant micelles at
      varying concentrations of sodium chloride (NaCl) or sodium salicylate (NaSal).
      The shape and structure of micelles are not subject to external constraints.
      NaSal is significantly more efficient in screening the intermicelle repulsive
      interactions shown by the PMF compared to NaCl due to a stronger binding of
      salicylate counterions to the micelle corona. Upon contact with each other, the
      micelles coalesce in the presence of NaSal to form a cylindrical structure which
      is stabilized by the adsorbed salicylate anions. Comparison of the PMF with
      Derjaguin-Landau-Verwey-Overbeek (DLVO) potentials shows qualitative agreement,
      while the magnitude of PMF is significantly greater than that of the DLVO
      potentials. To understand this discrepancy, PMF is evaluated by turning off (a)
      long-ranged electrostatic interactions and (b) solvent polarizability. The above
      effects are shown to play an important role in determining the solvent-mediated
      and ion-correlated interactions between the two micelles, which are not
      explicitly captured by mean-field double layer theories such as DLVO.

PMID- 22149606
TI  - Global positive expectancies in adolescence and health-related behaviours:
      longitudinal models of latent growth and cross-lagged effects.
AB  - Constructs representative of global positive expectancies (GPE) such as
      dispositional optimism and hope have been theoretically and empirically linked to
      many positive mental and physical health outcomes. However such expectancies'
      health implications for adolescents, as well as their trajectory over time, are
      less well understood than for adult populations. This study tested whether GPE
      predict the key indicators of adolescents' future physical health status, their
      health-related behaviours. A prospective longitudinal study design was employed
      whereby a diverse population-based cohort (N = 744; mean age at baseline = 12)
      completed three surveys over approximately 18 months. Rigorous tests of causal
      predominance and reciprocal effects were conducted through latent growth and
      cross-panel structural equation models. Results showed GPE systematically
      decreased during the course of the study, yet higher initial levels of GPE
      predicted less alcohol drinking, healthier food choice and greater physical
      activity over time. GPE's protective relationships towards health protective
      behaviours (vs. health risk behaviours that also included tobacco smoking) appear
      more independent from depressive symptomatology, and the primary findings were
      robust across socio-demographic groups.

PMID- 22149607
TI  - 'Flesh-eating' necrotizing infections: must we amputate?

PMID- 22149608
TI  - Why is the response rate slow in ceftazidime therapy for melioidosis?

PMID- 22149610
TI  - Elvitegravir: a once-daily, boosted, HIV-1 integrase inhibitor.
AB  - The development of HIV-1 integrase strand transfer inhibitors (INSTIs) has been a
      major therapeutic breakthrough in the management of HIV-1 infection. The first
      HIV-1 integrase inhibitor, raltegravir, was licensed in 2007 and was subsequently
      approved for use in treatment-naive patients. Since then, newer members of the
      INSTI class have been developed, including elvitegravir (EVG), which is in
      advanced clinical development and is being developed for use in both treatment
      naive and treatment-experienced patients. EVG utilizes pharmacokinetic boosting
      to achieve adequate serum levels with once-daily dosing. Boosting agents with
      which it is being studied include ritonavir and cobicistat. In addition, EVG is
      being studied as a once-daily INSTI in a coformulated fixed-dose combination pill
      with the agents tenofovir disoproxil fumarate, emtricitabine and cobicistat (QUAD
      pill), which has the additional potential benefit of convenient once-daily
      dosing. The in vitro activity, pharmacokinetic and pharmacodynamic properties,
      results of Phase I-III clinical trials, resistance profile and drug-drug
      interactions of EVG will be reviewed in this article.

PMID- 22149611
TI  - Nevirapine extended-release for the treatment of HIV-1 infection.
AB  - Non-nucleoside antiretroviral combination therapy is the standard of care with a
      robust virologic efficacy and a good safety profile. One of the most frequently
      used non-nucleosides, nevirapine (NVP), has been available as a every 12 h,
      immediate-release (IR) tablet since 1996. In order to enhance convenience and
      adherence, a new pharmaceutical formulation was devised for once-daily use. This
      is the NVP extended-release (XR) tablet containing 400 mg of NVP. Preclinical and
      clinical studies were performed to establish the optimal pharmaceutical release
      form and to establish data on comparability with the conventional NVP-IR. The
      VERXVE study has shown noninferiority of the new NVP-XR formulation in treatment
      naive patients. Safety and tolerability was found to be at least as good as with
      NVP-IR. NVP-XR is likely to become a convenient treatment option in first-line
      therapy and will also be a welcome alternative to patients already on NVP.

PMID- 22149612
TI  - Diagnosing acute HIV infection.
AB  - Individuals with acute HIV infection (AHI) pose a greater transmission risk than
      most chronically HIV-infected patients and prevention efforts targeting these
      individuals are important for reducing the spread of HIV infection. Rapid and
      accurate diagnosis of AHI is crucial. Since symptoms of AHI are nonspecific, its
      diagnosis requires a high index of suspicion and appropriate HIV laboratory
      tests. However, even 30 years after the start of the HIV epidemic, laboratory
      tools remain imperfect and only a few individuals with AHI are identified. We
      review the clinical presentation of the acute retroviral syndrome, the laboratory
      markers and their detection methods, and propose an algorithm for the laboratory
      diagnosis of AHI.

PMID- 22149613
TI  - Interventions to reduce mortality in sub-Saharan Africa among HIV-infected adults
      not yet on antiretroviral therapy.
AB  - Where antiretroviral therapy is available, the primary source of mortality among
      HIV-infected people is the delay in starting treatment. Many of these delays
      occur in the context of care and are modifiable through changes in the protocols
      followed by healthcare providers for HIV testing, staging and preparation of
      patients for antiretroviral therapy. A number of potential evidence-based
      interventions are discussed in the context of sub-Saharan Africa. Included are
      decentralizing services, initiating counseling on antiretroviral therapy without
      delay, tracing patients that miss appointments, protecting patient
      confidentiality, reducing user fees, and providing point-of-care tests for CD4
      cell counts, cryptococcal antigen, and for the diagnosis of TB.

PMID- 22149614
TI  - Advances in cytomegalovirus-preventive strategies in solid organ transplantation:
      defending pre-emptive therapy.
AB  - Prevention of cytomegalovirus (CMV) infection is an important part of clinical
      care provided to patients after solid organ transplantation. While the optimal
      preventive strategy has not been defined, most centers rely on universal
      prophylaxis or pre-emptive therapy. This article comments on recent studies
      designed to identify strategies that effectively reduce the incidence of late
      onset CMV disease as the main problem associated with prophylaxis, and on recent
      data regarding the development of CMV-specific immunity depending on the CMV
      preventive regimen used. Despite an apparent trend to prefer prophylaxis in
      clinical practice, this approach does not seem to be based on robust evidence.

PMID- 22149615
TI  - Antimicrobial stewardship programs: methods of operation and suggested outcomes.
AB  - The judicious use of antibiotics is an important strategy to preserving efficacy
      in the treatment of infectious diseases. Infectious disease practitioners are
      poised to provide patient-specific recommendations for appropriate agents and to
      optimize dosage and duration of therapy. Antimicrobial stewardship programs
      (involving pharmacists, physicians and other healthcare providers) are increasing
      in number as antibiotic resistance increases with a disproportionately small
      number of new agents being developed. Two strategies for antimicrobial
      stewardship are currently endorsed by national organizations and include
      preauthorization/formulary restriction and prospective audit with feedback. As it
      is important for programs to choose appropriate clinical and financial outcomes
      goals in order to assure sustainability, we review these strategies and discuss
      the impact of each on clinical outcomes and costs.

PMID- 22149616
TI  - Trachoma and antibiotic use: the 'A' in SAFE.
AB  - Trachoma, a chronic conjunctivitis caused by Chlamydia trachomatis, is the
      leading infectious cause of blindness worldwide. In recognition of this public
      health problem, the World Health Assembly has targeted the year 2020 to eliminate
      blinding trachoma, and a multifaceted strategy (SAFE) is recommended, including
      antibiotics for treatment of infection. Trachoma is a disease of entire
      communities, and the pool of infection resides largely in preschool age children.
      Thus, for endemic communities, mass treatment with antibiotics annually for at
      least 3-5 years is carried out. The antibiotics used, the effectiveness of this
      approach, and the challenges of antibiotic treatment of communities are
      discussed, concluding with a view towards the elimination of trachoma in the
      future.

PMID- 22149617
TI  - Candida albicans dimorphism as a therapeutic target.
AB  - The ability to switch between yeast and hyphal growth forms (dimorphism) is one
      of the most discussed and best investigated virulence attributes of the human
      pathogenic fungus Candida albicans. Both morphological forms seem to be important
      for virulence and have distinct functions during the different stages of disease
      development, including adhesion, invasion, damage, dissemination, immune evasion
      and host response. In this review, we will provide an overview of the known and
      potential roles of C. albicans dimorphism and will discuss the potential benefit
      of drugs that can inhibit the morphological transition.

PMID- 22149618
TI  - Infectious diseases following natural disasters: prevention and control measures.
AB  - Natural disasters may lead to infectious disease outbreaks when they result in
      substantial population displacement and exacerbate synergic risk factors (change
      in the environment, in human conditions and in the vulnerability to existing
      pathogens) for disease transmission. We reviewed risk factors and potential
      infectious diseases resulting from prolonged secondary effects of major natural
      disasters that occurred from 2000 to 2011. Natural disasters including floods,
      tsunamis, earthquakes, tropical cyclones (e.g., hurricanes and typhoons) and
      tornadoes have been secondarily described with the following infectious diseases
      including diarrheal diseases, acute respiratory infections, malaria,
      leptospirosis, measles, dengue fever, viral hepatitis, typhoid fever, meningitis,
      as well as tetanus and cutaneous mucormycosis. Risk assessment is essential in
      post-disaster situations and the rapid implementation of control measures through
      re-establishment and improvement of primary healthcare delivery should be given
      high priority, especially in the absence of pre-disaster surveillance data.

PMID- 22149620
TI  - Evaluation of rehabilitated bilateral lower limb amputees - an Indian study.
AB  - OBJECTIVE: This study assessed activities of daily living (ADL) and ambulation of
      rehabilitated bilateral lower limb amputees with relation to their level of
      amputation in an Indian setting. SUBJECTS AND METHODS: This retrospective study
      of 25 subjects comprised 12 bilateral Trans-femoral (TF) amputees, 8 bilateral
      Trans-tibial (TT) amputees and 5 a combination of ipsilateral Trans-femoral and
      contralateral Trans-tibial amputation. All subjects were contacted by
      post/telephone, were physically examined and assessed at the Orthopaedic clinic
      at a mean follow-up of 6.6 years. Physical rehabilitation was evaluated using ADL
      score and by grading the level of ambulation. RESULTS: ADL scores showed no
      significant difference according to level of amputation (p > 0.05), but the
      scores of prosthetic users were significantly higher than non-prosthetic users (p
      = 0.002). Only 11/25 amputees became prosthetic ambulators and most (50%, 6/12)
      were TF amputees. All prosthetically rehabilitated subjects were mobilising with
      their prostheses at follow-up and graded as unlimited or limited community
      ambulators. CONCLUSION: Though it is well documented that the potential for
      successful rehabilitation is best for bilateral TT amputees, given the subjects'
      economic constraints, higher prosthesis rehabilitation among bilateral TF
      amputees indicates that successful rehabilitation is possible in most subjects
      irrespective of the level of amputation.

PMID- 22149621
TI  - Cordycepin inhibits albumin-induced epithelial-mesenchymal transition of renal
      tubular epithelial cells by reducing reactive oxygen species production.
AB  - Albumin induced epithelial-mesenchymal transition (EMT) of renal tubular cells
      through reactive oxygen species (ROS) pathway plays an important role in
      tubulointerstitial fibrosis. Cordycepin (3 -deoxyadenosine), a potential
      antioxidant, was demonstrated to have various pharmacological effects and could
      inhibit EMT of some cells. However, the role of cordycepin on albumin-induced EMT
      in renal tubular cells (HK2) is unclear. In this study, we investigated the
      effect of cordycepin on albumin-induced EMT of HK2 cells and its mechanisms. HK-2
      cells were exposed to bovine serum albumin with or without pretreatment with
      cordycepin. Results showed that albumin significantly induced EMT formation of HK
      2 which associated with NADPH oxidase activation and intracellular ROS
      overproduction through increased Rac1 activity and expression of NOX4, p22phox
      and p47phox, while these effects were abolished in that pretreated with
      cordycepin. In conclusion, cordycepin could ameliorate albumin-induced EMT of HK2
      cells by decreasing NADPH oxidase activity and inhibiting ROS production.

PMID- 22149622
TI  - The influence of pH levels on mechanical and biological properties of nonlatex
      and latex elastics.
AB  - OBJECTIVE: To evaluate the influence of pH levels on interarch elastics with
      regard to force decay and cytotoxicity. MATERIALS AND METHODS: One nonlatex
      (NLAO) group and one latex (LAO) group were tested (n  =  10). Elastics were
      stretched to 25 mm and were held for 1, 6, 12, and 24 hours in artificial saliva
      solutions with pH levels of 5.0, 6.0, and 7.5. Force magnitudes were measured at
      25 mm of activation. The cytotoxicity assay was performed using cell cultures
      (L929 mouse fibroblast cell line), which were subjected to the cell viability
      test with neutral red ("dye-uptake"). Force decay and cytotoxicity were assessed
      using analysis of variance, the Sidak method, and a Tukey's test. RESULTS: The
      interactions between group, pH, and time showed no statistically significant
      differences (P  =  .29). When pH per time (P  =  .032) and group per time (P  = 
      .0009) were considered, these interactions showed statistically significant
      differences (P < .05). The pH did not interfere directly in the degradation
      results of the tested elastics. The cytotoxicity test showed that group LAO
      presented lower cell viability when compared with group NLAO over the course of
      the entire experiment. There was a gradual reduction in cell viability from 1
      hour to 24 hours. A significant difference (P < .05) was found between the
      interactions group pH and the control group of cells, except between group NLAO
      at the time point of 1 hour at different pH values and at the time points of 6
      and 12 hours with pH 5 (P > .05). CONCLUSIONS: No significant correlation between
      pH, force decay, and cytotoxicity was observed.

PMID- 22149623
TI  - Prediction of orthodontic treatment of surgically exposed unilateral maxillary
      impacted canine patients.
AB  - OBJECTIVE: To determine whether clinical variables associated with surgically
      exposed unilateral maxillary impacted canine cases are predictors for orthodontic
      treatment choices involving (1) extraction, (2) expansion, (3) extraction and
      expansion, or (4) nonextraction and nonexpansion. MATERIALS AND METHODS: A
      retrospective study of records of 97 cases meeting the inclusion criteria with
      unilateral maxillary impacted canines from three private practices were reviewed
      for gender, age, molar classification, impaction location and angulation, and
      presence of pretreatment maxillary and mandibular casts and cephalograms.
      Maxillary and mandibular transverse dimensions and lower incisor crowding were
      obtained from occlusal cast images using custom computer software. Skeletal
      analysis and incisor angulation and position were obtained from digitized
      cephalometric tracings. Statistical comparisons were made to determine parameters
      orthodontists could use to develop an orthodontic treatment plan. RESULTS:
      Subjects with Class II end-on molars on the nonaffected side were less likely to
      have extraction and/or expansion. Subjects with extraction and/or expansion had
      decreased lower incisor to mandibular plane, available canine space, maxillary
      premolars, and molar transverse dimensions and an increased mandibular incisor
      Irregularity Index compared with nonextraction/nonexpansion subjects. Using a
      multiple-variable model, available canine space was the single most important
      predictor of extraction and/or expansion, followed by maxillary molar transverse
      dimension and mandibular incisor Irregularity Index. CONCLUSIONS: Available
      canine space, maxillary transverse dimension at the molars, and the mandibular
      incisor Irregularity Index serve as indicators for extraction and/or expansion in
      cases involving unilateral maxillary impacted canines requiring surgical
      exposure. Many of these cases are treated without extraction and/or expansion.

PMID- 22149625
TI  - Clinic blood pressure, ambulatory blood pressure and cardiac structural
      alterations in nonagenarians and in centenarians.
AB  - scant information is available on the alterations in cardiac structure and
      function characterizing very elderly people as well as on their relationships to
      clinic and ambulatory blood pressure (BP) values. In 106 subjects aged 95.3 +/-
      3.7 years (mean +/- standard deviation, 89 nonagenarians and 17 centenarians) in
      good clinical conditions and living in the municipal house in Milan, we measured,
      along with standard clinical and laboratory variables, clinic BP, 24-h ambulatory
      BP and echocardiographic parameters. Forty-five of the recruited subjects were
      normotensive individuals, whereas 61 were treated hypertensive patients. Subjects
      with an age greater than 90 years showed clinic systolic (SBP) and diastolic BP
      (DBP) both within the normal range, with values that for clinic SBP were slightly
      lower than the corresponding 24-h SBP (120.8 +/- 15.9 vs 128.0 +/- 16.3 mmHg) and
      for DBP slightly higher (69.7 +/- 8.8 vs 64.9 +/- 8.0 mmHg). Daytime average mean
      BP was slightly lower than night-time average mean BP, indicating the attenuation
      of the BP reduction during night-time. Left ventricular mass index (LVMI) was
      increased and significantly related to both 24-h and clinic BP values (r = 0.24,
      p < 0.04 and r = 0.20, p < 0.05). Thus in nonagenarians and centenarians,
      abnormalities in left ventricular pattern are of frequent detection and may be
      related both to the ageing process and to BP load.

PMID- 22149624
TI  - An integrated stochastic model of "inside-out" integrin activation and selective
      T-lymphocyte recruitment.
AB  - The pattern of T-lymphocyte homing is hypothesized to be controlled by
      combinations of chemokine receptors and complementary chemokines. Here, we use
      numerical simulation to explore the relationship among chemokine potency and
      concentration, signal transduction, and adhesion. We have developed a form of
      adhesive dynamics-a mechanically accurate stochastic simulation of adhesion-that
      incorporates stochastic signal transduction using the next subvolume method. We
      show that using measurable parameter estimates derived from a variety of sources,
      including signaling measurements that allow us to test parameter values, we can
      readily simulate approximate time scales for T-lymphocyte arrest. We find that
      adhesion correlates with total chemokine receptor occupancy, not the frequency of
      occupation, when multiple chemokine receptors feed through a single G-protein. A
      general strategy for selective T-lymphocyte recruitment appears to require low
      affinity chemokine receptors. For a single chemokine receptor, increases in
      multiple cross-reactive chemokines can lead to an overwhelming increase in
      adhesion. Overall, the methods presented here provide a predictive framework for
      understanding chemokine control of T-lymphocyte recruitment.

PMID- 22149626
TI  - Increased levels of serum granulocyte-macrophage colony-stimulating factor is
      associated with activated peripheral dendritic cells in type 2 diabetes subjects
      (CURES-99).
AB  - BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro
      inflammatory cytokine with growth factor-like properties for monocytes and
      dendritic cells (DCs). In the present study, serum GM-CSF levels and the
      activation status of DCs were studied in type 2 diabetes mellitus (T2DM)
      subjects. METHODS: Study subjects were recruited from the Chennai Urban Rural
      Epidemiology Study. Healthy controls (n=45) and T2DM patients (n=45) were
      included in the study. Serum levels of GM-CSF, interleukin-1beta, interleukin-6,
      and tumor necrosis factor-alpha were measured. Enumeration of circulating DCs
      (myeloid [m] and plasmocytoid [p]) and its surface antigen expression were
      quantified by flow cytometry. RESULTS: The serum GM-CSF levels were significantly
      higher among diabetes subjects compared with subjects without diabetes and showed
      a positive correlation with glycated hemoglobin (r=0.208, P=0.018). The serum GM
      CSF levels were lower in subjects on combined insulin and oral hypoglycemic
      agents (OHA) treatment (1.09 pg/mL) compared with those taking OHA alone (1.9
      pg/mL). The increased GM-CSF levels were associated with the activated phenotype
      of mDCs and pDCs, as determined by up-regulation of the lineage markers.
      CONCLUSION: The activated state of mDCs and pDCs seen among diabetes subjects
      might be due to the increased levels of GM-CSF and other pro-inflammatory
      cytokines.

PMID- 22149627
TI  - Is the response of continuous glucose monitors to physiological changes in blood
      glucose levels affected by sensor life?
AB  - BACKGROUND: None of the studies concerned with the performance of a continuous
      glucose monitor (CGM) over time has examined the extent to which extended periods
      of wear affect the responses of both CGM accuracy and lag time to rapid changes
      in blood glucose levels. Here we propose a novel approach to address these
      issues. METHODS: Eight participants without diabetes were each fitted with two
      CGMs (Paradigm((r)) 722 Real-Time [Medtronic, Northridge, CA]; abdominal and
      triceps regions) and completed fasted oral glucose challenges (OGCs) on six
      occasions over a 9-day period, while the CGMs were worn without removal.
      Arterialized blood samples were collected for comparison with CGM values.
      RESULTS: There were marked mismatches and lag times between blood glucose and CGM
      values in response to all OGCs, most notably during the initial rapid increase in
      glucose levels. Abdominal and triceps CGMs consistently underestimated peak blood
      glucose by an average of 2.7+/-0.2 and 2.9+/-0.2 mM, respectively, and were
      associated with a peak blood glucose lag of 21.6+/-1.8 and 18.1+/-1.6 min,
      respectively. CGM accuracy did not deteriorate over 9 days of wear in OGCs for
      either the abdominal or triceps sensor. All participants found the triceps sensor
      site more comfortable than the abdominal site (P<0.05). CONCLUSIONS: The current
      CGM sensor tested here may be used for extended periods, providing added economic
      benefits for the wearer. However, the marked inaccuracy and lag time of CGM
      readings when blood glucose levels change rapidly within the physiological range
      must be considered for optimal CGM use in glycemic management.

PMID- 22149628
TI  - Comparison of konjac glucomannan digestibility and fermentability with other
      dietary fibers in vitro.
AB  - Konjac glucomannan (KGM) is a dietary fiber found in Amophophallus konjac. This
      fiber is fermentable based on human and animal trials, but short-chain fatty acid
      (SCFA) production profiles are unknown. The aim of this study is to characterize
      the digestibility and fermentability in vitro of two preparations of KGM, to
      better understand how KGM improves human health. Konnyaku (yam cake made of A.
      konjac), isolated KGM, inulin, and guar gum were subjected to in vitro digestion
      and in vitro fermentation. Fermentation samples were removed at 0, 4, 8, 12, and
      24 hours for gas volume, pH, and SCFA measurements. Acetate, propionate, and
      butyrate were measured with gas chromatography. Results of the in vitro digestion
      confirm that KGM and konnyaku are resistant to degradation by digestive enzymes.
      Gas production in fermentation vessels containing konnyaku and KGM was lower than
      for inulin from 8 to 24 hours. Both samples produced SCFA concentrations similar
      to guar gum, which favored acetate and propionate over butyrate production. This
      study is the first to characterize SCFA production by KGM in its isolated form
      and in food form. Fermentation patterns presented in this study may provide a
      mechanism for the previously published health benefit of konnyaku and KGM.

PMID- 22149629
TI  - Nano-organized collagen layers obtained by adsorption on phase-separated polymer
      thin films.
AB  - The organization of adsorbed type I collagen layers was examined on a series of
      polystyrene (PS)/poly(methyl methacrylate) (PMMA) heterogeneous surfaces obtained
      by phase separation in thin films. These thin films were prepared by spin coating
      from solutions in either dioxane or toluene of PS and PMMA in different
      proportions. Their morphology was unraveled combining the information coming from
      X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and water
      contact angle measurements. Substrates with PMMA inclusions in a PS matrix and,
      conversely, substrates with PS inclusions in a PMMA matrix were prepared, the
      inclusions being either under the form of pits or islands, with diameters in the
      submicrometer range. The organization of collagen layers obtained by adsorption
      on these surfaces was then investigated. On pure PMMA, the layer was quite smooth
      with assemblies of a few collagen molecules, while bigger assemblies were found
      on pure PS. On the heterogeneous surfaces, it appeared clearly that the diameter
      and length of collagen assemblies was modulated by the size and surface coverage
      of the PS domains. If the PS domains, either surrounding or surrounded by the
      PMMA phase, were above 600 nm wide, a heterogeneous distribution of collagen was
      found, in agreement with observations made on pure polymers. Otherwise, fibrils
      could be formed, that were longer compared to those observed on pure polymers.
      Additionally, the surface nitrogen content determined by XPS, which is linked to
      the protein adsorbed amount, increased roughly linearly with the PS surface
      fraction, whatever the size of PS domains, suggesting that adsorbed collagen
      amount on heterogeneous PS/PMMA surfaces is a combination of that observed on the
      pure polymers. This work thus shows that PS/PMMA surface heterogeneities can
      govern collagen organization. This opens the way to a better control of collagen
      supramolecular organization at interfaces, which could in turn allow cell
      material interactions to be tailored.

PMID- 22149630
TI  - Cerebral blood flow and neuropsychological functioning in elderly vascular
      disease patients.
AB  - This study was designed to determine the relationships between positron emission
      tomography (PET)-based quantitative measures of cerebral blood flow and
      cerebrovascular reserve and neuropsychological functioning in elderly individuals
      with atherosclerotic vascular disease. It was hypothesized that cerebrovascular
      function would be significantly associated with neuropsychological functioning.
      Results showed that both baseline global cerebral blood flow and cerebrovascular
      reserve were significantly associated with global neuropsychological functioning,
      when controlling for age and sex. Cerebrovascular reserve was additionally
      associated with performance on measures of memory and attention. Additional
      research is needed to determine whether measures of cerebral blood flow can be
      used to predict cognitive decline.

PMID- 22149631
TI  - Incorporating calibrated model parameters into sensitivity analyses:
      deterministic and probabilistic approaches.
AB  - OBJECTIVE: The aim of this study was to examine how calibration uncertainty
      affects the overall uncertainty of a mathematical model and to evaluate potential
      drivers of calibration uncertainty. METHODS: A lifetime Markov model of the
      natural history of human papillomavirus (HPV) infection and cervical disease was
      developed to assess the cost effectiveness of a hypothetical HPV vaccine.
      Published data on cervical cancer incidence and mortality and prevalence of pre
      cursor lesions were used as endpoints to calibrate the age- and HPV-type-specific
      transition probabilities between health states using the Nelder-Mead simplex
      method of calibration. A conventional probabilistic sensitivity analysis (PSA)
      was performed to assess uncertainty in vaccine efficacy, cost and utility
      estimates. To quantify the uncertainty around calibrated transition
      probabilities, a second PSA (calibration PSA) was performed using 25 distinct
      combinations of objective functions and starting simplexes. RESULTS: The initial
      calibration produced an incremental cost-effectiveness ratio (ICER) of $US 4300
      per QALY for vaccination compared with no vaccination, and the conventional PSA
      gave a 95% credible interval of dominant to $US 9800 around this estimate (2005
      values). The 95% credible interval for the ICERs in the calibration PSA ranged
      from $US 1000 to $US 37,700. CONCLUSIONS: Compared with a conventional PSA, the
      calibration PSA results reveal a greater level of uncertainty in cost
      effectiveness results. Sensitivity analyses around model calibration should be
      performed to account for uncertainty arising from the calibration process.

PMID- 22149632
TI  - Separating significant matches from spurious matches in DNA sequences.
AB  - Word matches are widely used to compare genomic sequences. Complete genome
      alignment methods often rely on the use of matches as anchors for building their
      alignments, and various alignment-free approaches that characterize similarities
      between large sequences are based on word matches. Among matches that are
      retrieved from the comparison of two genomic sequences, a part of them may
      correspond to spurious matches (SMs), which are matches obtained by chance rather
      than by homologous relationships. The number of SMs depends on the minimal match
      length (l) that has to be set in the algorithm used to retrieve them. Indeed, if
      l is too small, a lot of matches are recovered but most of them are SMs.
      Conversely, if l is too large, fewer matches are retrieved but many smaller
      significant matches are certainly ignored. To date, the choice of l mostly
      depends on empirical threshold values rather than robust statistical methods. To
      overcome this problem, we propose a statistical approach based on the use of a
      mixture model of geometric distributions to characterize the distribution of the
      length of matches obtained from the comparison of two genomic sequences.

PMID- 22149633
TI  - Statistical significance of threading scores.
AB  - We present a general method for assessing threading score significance. The
      threading score of a protein sequence, thread onto a given structure, should be
      compared with the threading score distribution of a random amino-acid sequence,
      of the same length, thread on the same structure; small p-values point
      significantly high scores. We claim that, due to general protein contact map
      properties, this reference distribution is a Weibull extreme value distribution
      whose parameters depend on the threading method, the structure, the length of the
      query and the random sequence simulation model used. These parameters can be
      estimated off-line with simulated sequence samples, for different sequence
      lengths. They can further be interpolated at the exact length of a query,
      enabling the quick computation of the p-value.

PMID- 22149639
TI  - A classification and regression tree analysis for the evaluation of the role of
      nutritional services on cardiovascular disease risk status of older people living
      in Greek islands and Cyprus.
AB  - INTRODUCTION: The purpose of this study was to evaluate, with classification
      regression tree analysis, the structure of the associations between nutritional
      and health care services and the cumulative prevalence of the classical
      cardiovascular disease (CVD) risk factors of older individuals living in Greek
      islands and Cyprus. METHODS: During 2005-2009, 744 men and 742 women (>65 years)
      from nine Greek islands and Cyprus Republic were voluntarily enrolled in the
      Mediterranean Islands study; various socio-demographic, clinical and lifestyle
      characteristics were recorded. Moreover, information regarding practising
      dieticians (n = 88) and nutritional services provided in these islands was also
      recorded. RESULTS: Both medical and nutrition services act more effectively to
      elders' cardiovascular health. For example, older individuals living in areas
      with nutritional services' support for at least five years, with collaboration
      between dieticians and physicians, reduced the CVD risk factors (CVD RF) burden
      by 42%. Whereas, in areas with dietetic support less than five years, but more
      than two, the presence of advanced health care system seemed to control the CVD
      RF burden to the population average. CONCLUSIONS: Despite the fact that the
      present work shares some limitations mainly because of its cross-sectional
      design, the classification and regression tree approach has clearly demonstrated
      the interrelation between nutritional services and the health care system towards
      achieving benefits among the elders' quality of life.

PMID- 22149640
TI  - Juxtafoveal choroidal neovascularization associated with retinitis pigmentosa
      treated with intravitreal bevacizumab.
AB  - PURPOSE: To describe a case of juxtafoveal choroidal neovascularization (CNV)
      occurring in a patient affected by retinitis pigmentosa (RP), treated with
      intravitreal bevacizumab over a 12-month follow-up. METHODS: A 66 year-old woman
      referred to our center for visual acuity deterioration was diagnosed as having
      classic juxtafoveal CNV associated with RP. The patient was treated with
      intravitreal bevacizumab, and was regularly monitored every month. RESULTS: At
      the end of the 12-month follow-up, best corrected visual acuity changed from
      20/200 to 20/100 in the affected eye. Five intravitreal bevacizumab injections
      were required to obtain the stabilization of the CNV. CONCLUSIONS: Intravitreal
      bevacizumab is effective in producing juxtafoveal CNV stabilization and visual
      acuity improvement in a patient affected by RP, over a 12-month follow-up. Future
      studies are required to ascertain the best therapeutic approach for CNV
      complicating RP.

PMID- 22149641
TI  - Effect of mechanical stimulation on the differentiation of cord stem cells.
AB  - In this study, we evaluated the effect of mechanical stimulation on the
      differentiation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in
      osteogenic medium using a Flexcell system that imposed cyclic uniaxial mechanical
      stimulation at a strain of 0%, 5%, or 10% (5 s of stretch and 15 s of relaxation)
      for 10 days. The expression of MSC surface antigens (CD73, CD90, and CD105) was
      significantly decreased as strain increased. Mechanical stimulation inhibited the
      growth of UC-MSCs and slightly raised lactate dehydrogenase production.
      Mechanically stimulated groups produced more elastin and sulfated
      glycosaminoglycan than unstimulated groups and these increases were in proportion
      to the degree of strain. Reverse transcription-polymerase chain reaction analysis
      revealed that mechanical stimulation induced a significant increase in the mRNA
      expression of osteoblast differentiation markers. The mRNA levels of osteopontin,
      osteonectin, and type I collagen in the 5% and 10% strained groups were
      significantly higher than those in the 0% strained group. From the Western blot
      analysis, UC-MSCs produced bone sialoprotein and vimentin in a mechanical strain
      dependent manner. Thus, cyclic mechanical loading was able to enhance the
      differentiation of human UC-MSCs into osteoblast-like cells as determined by
      osteogenic gene and protein expression. Furthermore, this finding has important
      implications for the use of the combination of mechanical and osteogenic
      differentiation media for UC-MSCs in tissue engineering and regenerative
      medicine.

PMID- 22149643
TI  - Vincristine-sulphate-loaded liposome-templated calcium phosphate nanoshell as
      potential tumor-targeting delivery system.
AB  - Vincristine-sulfate-loaded liposomes were prepared with an aim to improve
      stability, reduce drug leakage during systemic circulation, and increase
      intracellular uptake. Liposomes were prepared by the thin-film hydration method,
      followed by coating with calcium phosphate, using the sequential addition
      approach. Prepared formulations were characterized for size, zeta potential, drug
      entrapment efficiency, morphology by transmission electron microscopy (TEM), in
      vitro drug-release profile, and in vitro cell cytotoxicity study. Effect of
      formulation variables, such as drug:lipid ratio as well as nature and volume of
      hydration media, were found to affect drug entrapment, and the concentration of
      calcium chloride in coating was found to affect size and coating efficiency.
      Size, zeta potential, and TEM images confirmed that the liposomes were
      effectively coated with calcium phosphate. The calcium phosphate nanoshell
      exhibited pH-dependent drug release, showing significantly lower release at pH
      7.4, compared to the release at pH 4.5, which is the pH of the tumor
      interstitium. The in vitro cytotoxicity study done on the lung cancer cell line
      indicated that coated liposomes are more cytotoxic than plain liposomes and drug
      solution, indicating their potential for intracellular drug delivery. The cell
      uptake study done on the lung cancer cell line indicated that calcium-phosphate
      coated liposomes show higher cell uptake than uncoated liposomes.

PMID- 22149642
TI  - Comparison of total body irradiation before and after chemotherapy in
      pretreatment for hematopoietic stem cell transplantation.
AB  - OBJECTIVE: To explore the best time to carry out total body irradiation (TBI) in
      hematopoietic stem cell transplantation (HSCT) pretreatment. METHODS:
      Retrospective analysis was applied in 88 cases of HSCT using TBI as pretreatment
      from March 2001 to June 2009 in our hospital. Using 8 MV X-ray, all the patients
      were irradiated by linear accelerator in 2 consecutive days, with a total dose of
      7-11 Gy and an instantaneous dose rate ranging between 4.0 and 5.0 cGy/min. Of
      the 88 cases, 40 cases were given traditional high-dose chemotherapy before TBI
      (Group CT/TBI), and 48 cases were given TBI before chemotherapy (Group TBI/CT)
      instead. RESULTS: Eighty-seven cases of transplantation were successful, with no
      serious complications, including radiation pneumonia. Compared with Group CT/TBI,
      Group TBI/CT showed similar incidence of complications (p=0.08), similar recent
      chemotherapy toxicity (p=0.833), and significantly lower recent radiation
      toxicity (p=0.000). CONCLUSIONS: TBI in the pretreatment of HSCT is safe and
      effective. Using TBI before the high-dose chemotherapy can maintain the same
      pretreatment effect, effectively reduce apparent immediate reaction/discomfort
      during TBI, reduce preparation workload of radiotherapy, and lower radiation side
      effects. Further research is needed to expand its clinical application.

PMID- 22149644
TI  - Parental experience of childhood cancer using Interpretative Phenomenological
      Analysis.
AB  - Whilst survival rates for childhood cancer have improved dramatically over the
      past three decades, it is still a devastating diagnosis for family members and an
      illness which severely disrupts the lifestyle of the family unit. Developing an
      understanding of the impact of the illness on the family is crucial to better
      support families' deal with the demands of the illness. In this study nine
      families in which a child was diagnosed with cancer were interviewed twice over a
      12 month period, approximately 6 months apart. Using Interpretative
      Phenomenological Analysis, a semi-structured interview was used to explicate
      parent's experience of childhood cancer. The results revealed five super-ordinate
      themes; (1) a pivotal moment in time, (2) the experience of adaptation in
      relation to having a sick child, (3) the nature of support, (4) re-evaluation of
      values during a critical life experience and (5) the experience of optimism and
      altruism. Findings indicate that parents express both negative and positive
      experiences as they re-evaluate the meaning and purpose of life, seek to redefine
      themselves, often in terms of priorities, relationships, sense of community and
      achieve degrees of optimism and altruism. Implications for addressing the needs
      of parents and for further research are discussed.

PMID- 22149645
TI  - Collaboration: developing integration in multi-purpose  services in rural New
      South Wales, Australia.
AB  - INTRODUCTION: The Multi-purpose Service (MPS) Program was introduced to rural
      Australia in 1991 as a solution to poor health outcomes in rural compared with
      metropolitan populations, difficulty in attracting healthcare staff and a lack of
      viability and range of health services in rural areas. The aim of this study was
      to describe the main concerns of participants involved in the development of
      multi-purpose services in rural New South Wales (NSW). This article is abstracted
      from a larger study and discusses the extent to which collaboration occurred
      within the new multi-purpose service. METHODS: A constructivist grounded theory
      methodology was used. Participants were from 13 multi-purpose services in rural
      NSW and 30 in-depth interviews were conducted with 6 community members, 11
      managers and 13 staff members who had been involved in the process of developing
      a multi-purpose service. RESULTS: The main concern of all participants was their
      anticipation of risk. This anticipation of risk manifested itself in either trust
      or suspicion and explained their progression through a phase of collaborating.
      Participants who had trust in other stakeholders were more likely to embrace an
      integrated health service identity. Those participants, who were suspicious that
      they would lose status or power, maintained that the previous hospital services
      provided a better health service and described a coexistence of services within
      the multi-purpose service. CONCLUSIONS: This study provided an insight into the
      perceptions of community members, staff members and managers involved in the
      process of developing a multi-purpose service. It revealed that the anticipation
      of risk was intrinsic to a process of changing from a traditional hospital
      service to collaborating in a new model of health care provided at a multi
      purpose service.

PMID- 22149646
TI  - Rhodium(III)-catalyzed intermolecular direct amination of aromatic C-H bonds with
      N-chloroamines.
AB  - A Rh(III)-catalyzed direct aromatic C-H amination is achieved using N
      chloroamines as a reagent. Furthermore, we also developed a one-pot amination
      protocol involving in situ chlorination of the secondary amines. The catalytic
      amination operates at mild conditions with excellent functional group tolerance
      and regioselectivity.

PMID- 22149647
TI  - Total synthesis of nominal lyngbouilloside aglycon.
AB  - The first enantioselective total synthesis of the originally assigned structure
      of lyngbouilloside aglycon has been achieved using a particularly flexible route
      featuring an acylketene macrolactonization of a tertiary methyl carbinol as the
      key step. Comparison of the C13 chemical shifts of our synthetic aglycon with the
      ones pertaining to natural lyngbouilloside and lyngbyaloside C resulted in a
      possible stereochemical reassignment of the C11 stereogenic center.

PMID- 22149648
TI  - Living successfully with aphasia: a qualitative meta-analysis of the perspectives
      of individuals with aphasia, family members, and speech-language pathologists.
AB  - The concept of living successfully with aphasia has recently emerged as an
      alternative to more traditional "deficit" models in aphasiology, encouraging a
      focus on positive rather than negative outcomes. This research aimed to integrate
      findings from studies exploring the perspectives of three participant groups
      (individuals with aphasia, speech-language pathologists, and family members)
      about living successfully with aphasia. Qualitative meta-analysis of three
      studies conducted by the authors was used to integrate perspectives across the
      participant groups. Steps in the qualitative meta-analysis were based on those
      described in the process of "meta-ethnography" by  Noblit and Hare (1988) .
      Analysis was an inductive process, in which data from each study were re-analysed
      and translated into each other in order to identify higher-level overarching
      themes that accounted for similarities and discrepancies across the original
      studies. A total of seven overarching themes related to living successfully with
      aphasia were identified. These were: participation, meaningful relationships,
      support, communication, positivity, independence and autonomy, and living
      successfully with aphasia as a journey over time. Findings indicate the need for
      a holistic, client-centred approach that considers communication in the broader
      context of an individual's daily life. The overarching themes may act as guides
      for areas of importance to be addressed in clinical practice, as well as in
      future research. By working in partnership with individuals with aphasia and
      their families, speech-language pathologists are challenged to continue to
      improve services and assist clients on their journey of living successfully with
      aphasia.

PMID- 22149649
TI  - Phage-chips for novel optically readable tissue engineering assays.
AB  - We report novel phage-based array chips that are optically readable for cell
      proliferation and morphology assays. Using M13 phages that were engineered to
      display RGD on its major coat proteins and/or immobilize FGFb on its minor coat
      proteins, we prepared arrays of phage spot matrices composed of self-assembled
      nanofibrous network structures. We cultured fibroblasts on the arrays and, using
      surface plasmon resonance (SPR) spectroscopy, monitored the effects of the
      biochemical cues displayed by the phage on cell proliferation and morphology.
      This study demonstrates the utility of engineered phages as promising coating
      materials for lab-on-a-chip (LOC) platforms, allowing sensitive monitoring of the
      effects of functional peptides on cell growth. Phage-chips have great potential
      for use as high-throughput screening systems for biochemical assays and
      biosensors and the discovery of novel drugs.

PMID- 22149654
TI  - Nuclear and mitochondrial DNA oxidation in Alzheimer's disease.
AB  - The study of Alzheimer's disease neuropathology has been intimately associated
      with the field of oxidative stress for nearly 20 years. Indeed, increased markers
      of oxidative stress have been associated with this neurodegenerative condition,
      resulting from oxidation of lipids, proteins and nucleic acids. Increased nuclear
      and mitochondrial DNA oxidation are observed in Alzheimer's disease, stemming
      from increased reactive oxygen species attack to DNA bases and from the
      impairment of DNA repair mechanisms. Moreover, mitochondrial DNA is found to be
      more extensively oxidized than nuclear DNA. This review is intended to summarizes
      the most important cellular reactive oxygen species producers and how
      mitochondrial dysfunction, redox-active metals dyshomeostasis and NADPH oxidases
      contribute to increased oxidative stress in Alzheimer's disease. A summary of the
      antioxidant system malfunction will also be provided. Moreover, we will highlight
      the mechanisms of DNA oxidation and repair. Importantly, we will discuss evidence
      relating the DNA repair machinery and accumulated DNA oxidation with Alzheimer's
      disease.

PMID- 22149655
TI  - Biofouling resistance of ultrafiltration membranes controlled by surface self
      assembled coating with PEGylated copolymers.
AB  - Block and random PEGylated copolymers of poly(ethylene glycol) methacrylate
      (PEGMA) and polystyrene (PS) were synthesized with a controlled polydispersity
      using an atom transfer radical polymerization method and varying molar mass
      ratios of PS/PEGMA. Two types of PEGylated copolymers were self-assembly coated
      onto the surface of poly(vinylidene fluoride) (PVDF) ultrafiltration membranes
      for enhancing biofouling resistance. It was found that the adsorption capacities
      of random copolymers on PVDF membranes were all higher than those of block
      copolymers. However, the specific and overall protein resistance of bovine serum
      albumin (BSA) on PVDF membranes coated with block copolymers was much higher than
      that with random copolymers. The increase in styrene content in copolymer
      increased the amount of polymer coating on the membrane, and the increase in
      PEGMA content enhanced the protein resistance of membranes. The optimum PS/PEGMA
      ratio was found to be close to 2 for the best resistance of protein adsorption
      and bacterial adhesion on the PEGylated diblock copolymer-coated membranes. The
      PVDF membrane coated with such a copolymer owned excellent biofouling resistance
      to BSA, humic acid, negatively surface charged bacteria E. coli, and positively
      surface charged bacteria S. maltophilia.

PMID- 22149656
TI  - Fisher syndrome: clinical features, immunopathogenesis and management.
AB  - Since Miller Fisher's first report in 1956, evidence has accumulated about
      clinical and laboratory features, immunopathogenesis and treatment of Fisher
      syndrome (FS). Our literature review revealed the nature of FS. It has relatively
      uniform clinical and laboratory features. Ophthalmoplegia, ataxia and areflexia
      are essential prerequisites for an FS diagnosis, but there are several clinical
      variants with isolated ophthalmoplegia or ataxia. The discovery of serum anti
      GQ1b antibody in FS has led to breakthroughs in FS research. The antibody is
      thought to be a key factor in the pathogenesis of FS, the understanding of which
      has progressed owing to the discovery of molecular mimicry between GQ1b and the
      lipo-oligosaccharides of Campylobacter jejuni and Haemophilus influenzae. The
      lesions responsible for the clinical symptoms have been debated but are close to
      clarification. Hence, the pathogenesis of FS has been made much clearer, although
      there are still some unanswered questions.

PMID- 22149657
TI  - Potential therapeutic avenues to tackle social cognition problems in
      schizophrenia.
AB  - Therapeutic strategies for improving social cognition in patients with
      schizophrenia have shown much promise in improving social functioning, as well as
      remediating core psychotic symptoms. However, the efficacy of previous
      interventions has often been limited by the ambiguity and inconsistency of the
      categorized subdomains of social cognition, including theory of mind, emotion
      processing, social perception and attributional bias. Recent research in social
      and cognitive neuroscience has revealed many new issues that could contribute to
      the development of more integrated approaches for improving social functioning.
      The application of such neuroscientific work to a therapeutic and diagnostic
      context is likely to encourage more effective transference of learned skills to
      real-world social functioning. This article seeks to provide a comprehensive
      review of previous social cognitive interventions for schizophrenia, highlight
      some crucial limitations of these and present the relevance of recent advances in
      neuroscientific research in possible future treatment strategies. It is
      emphasized that a more integrated and naturalistic approach for improving social
      functioning with greater sensitivity for neuroscientific findings related to the
      psychopathology of schizophrenia is warranted.

PMID- 22149658
TI  - The use of newer antiepileptic drugs in patients with renal failure.
AB  - Seizures and chronic kidney disease are both common and often coexist. Treating
      seizures in patients with renal failure, including those on dialysis, is a
      challenge that is frequently encountered, especially in the inpatient setting.
      For the newer antiepileptic drugs, there are limited data available, so an
      understanding of how each drug is affected by kidney disease and dialysis is
      critical in order to make rational choices qualitatively (which drug) and
      quantitatively (dosing). Generally, newer (second-generation) antiepileptic drugs
      are associated with fewer systemic side effects and drug-drug interactions, so
      they tend to be preferred in this population. The landscape of antiepileptic
      drugs is constantly evolving, with new compounds being released on a regular
      basis. Thus, several new agents have become available since the last review of
      this topic (in 2006) and these are the ones discussed here. Most require dosage
      adjustment according to the degree of renal failure, and most require extra doses
      after dialysis.

PMID- 22149659
TI  - Metabolic-based drug-drug interactions prediction, recent approaches for risk
      assessment along drug development.
AB  - Prediction of in vivo drug-drug interactions (DDIs) from in vitro and in vivo
      data, also named in vitro in vivo extrapolation (IVIVE), is of interest to
      scientists involved in the discovery and development of drugs. To avoid
      detrimental DDIs in humans, new drug candidates should be evaluated for their
      possible interaction with other drugs as soon as possible, not only as an
      inhibitor or inducer (perpetrator) but also as a substrate (victim). DDI risk
      assessment is addressed along the drug development program through an iterative
      process as the features of the new compound entity are revealed. Both in vitro
      and preclinical/clinical outcomes are taken into account to better understand the
      behavior of the developed compound and to refine DDI predictions. During the last
      decades, several equations have been proposed in the literature to predict DDIs,
      from a quantitative point of view, showing a substantial improvement in the
      ability to predict metabolism-based in vivo DDIs. Mechanistic and dynamic
      approaches have been proposed to predict the magnitude of metabolic-based DDIs.
      The purpose of this article is to provide an overview of the current equations
      and methods, the pros and cons of each method, the required input data for each
      of them, as well as the mechanisms (i.e., reversible inhibition, mechanism-based
      inhibition, induction) underlying metabolic-based DDIs. In particular, this
      review outlines how the methods (static and dynamic) can be used in a
      complementary manner during drug development. The discussion of the limitations
      and advantages associated with the various approaches, as well as regulatory
      requirements in that field, can give the reader a helpful overview of this
      growing area.

PMID- 22149660
TI  - Interaction of human multidrug and toxin extrusion 1 (MATE1) transporter with
      antineoplastic agents.
AB  - BACKGROUND: The transport of endogenous and exogenous organic cations across the
      plasma membrane of cells is mediated by multispecific organic cation transporters
      (OCTs), and the multidrug and toxin extrusion (MATE) transporters. MATE belongs
      to the SLC47 transporter family consisting of only two members, MATE1 and MATE2
      K. MATE2-K is exclusively expressed in the kidney at the apical membrane of
      proximal tubular epithelial cells. MATE1 is highly expressed in the kidney,
      liver, skeletal muscle and also in adrenal glands, testes and heart. MATE1
      exchanges organic cations against protons both in influx as well as in efflux
      modes. METHODS: Here, we examined the interaction of 25 antineoplastic agents
      with human MATE1. We generated stably transfected MATE1-HEK293 cells and
      determined the inhibition of MATE1-mediated [(3)H]1-methyl-4-phenylpyridinium
      (MPP) uptake by the antineoplastic agents. RESULTS: We found a significant
      inhibition of MATE1-mediated MPP uptake by several antineoplastic agents and pH
      dependent IC(50)values for mitoxantrone (7.8 MUM at pH 7.4 and 0.6 MUM at pH 8.5)
      as well as for irinotecan (4.4 MUM at pH 7.4 and 1.1 MUM at pH 8.5),
      respectively. CONCLUSIONS: We suggest that hMATE1 could play a role in
      chemosensitivity of tumor cells. In addition, hepatic and renal MATE1 could
      potentially be involved in drug-drug-interactions as well as in drug metabolism
      and excretion during chemotherapy.

PMID- 22149661
TI  - Cytogenetic biomonitoring in children submitting to a complete set of radiographs
      for orthodontic planning.
AB  - OBJECTIVES: To evaluate the DNA damage (micronucleus) and cellular death
      (pyknosis, karyolysis, and karyorrhexis) in exfoliated buccal mucosa cells from
      children undergoing orthodontic radiographs. MATERIALS AND METHODS: A total of 25
      healthy children undergoing orthodontic therapy partook in a complete set of
      orthodontic radiographs (lateral cephalographic, posteroanterior cephalographic,
      panoramic, full periapical exam, and bitewing). The micronucleus test in the
      buccal exfoliated cells was applied. The paired-samples t-test and the Wilcoxon
      test were used to compare the frequencies of alterations before and after X-ray
      exposure. RESULTS: We found no statistically significant differences (P > .05)
      between micronucleated buccal mucosa cells before and after exposure to
      radiation. However, radiation did cause other nuclear alterations closely related
      to cytotoxicity (P  =  .007). CONCLUSION: According to the micronucleus test, the
      complete set of radiographs requested in the orthodontic planning may not be a
      factor that induces chromosomal damage, but it is able to promote cytotoxicity.

PMID- 22149662
TI  - Perception of the esthetic impact of mandibular incisor extraction treatment on
      laypersons, dental professionals, and dental students.
AB  - OBJECTIVE: To evaluate the degree of perception of laypersons, dental
      professionals, and dental students regarding dental esthetics in cases with
      mandibular central incisor extraction. MATERIALS AND METHODS: Using a smile
      photograph of a person with normal occlusion and all teeth, modifications were
      made to reflect the extraction of a mandibular incisor of various compositions
      and sizes. For this purpose a program specifically for image manipulation (Adobe
      Photoshop CS3, Adobe Systems Inc) was used. After manipulation the images were
      printed on photographic paper, attached to a questionnaire and distributed to
      laypersons, dental professionals, and dental students (n  =  90) to evaluate the
      degree of perception and esthetic using a scale of attractiveness, where 0  = 
      hardly attractive, 5  =  attractive, and 10  =  very attractive. The differences
      between examiners were checked by the Mann-Whitney test. All the statistics were
      performed with a confidence level of 95%. RESULTS: The results demonstrated the
      skill of the dental professionals and dental students in perceiving the
      difference between cases of normal occlusion and cases where an incisor was
      lacking (P < .05). The photograph in which the lateral incisors were shown to be
      larger than the central incisor was the one that obtained the highest value among
      the cases of extraction in all groups of evaluators. CONCLUSIONS: It can be
      concluded that dental professionals and dental students are more skillful at
      identifying deviation from normality. In addition, central incisor extraction
      should always be discarded when there are other treatment options available.

PMID- 22149663
TI  - Management and outcomes of suction loss during LASIK flap creation with a
      femtosecond laser.
AB  - PURPOSE: To evaluate risk factors, management, and outcomes in patients who
      experienced suction loss during LASIK flap creation with a femtosecond laser
      (Intra-Lase FS 60, Abbott Medical Optics Inc). METHODS: Pre- and postoperative
      visual outcomes and refractions for 71 eyes of 70 patients after suction loss
      during flap creation with the IntraLase FS60 femtosecond laser were analyzed and
      studied. RESULTS: In patients requiring a second or third lamellar flap cut
      immediately after suction loss, 97.2% of eyes achieved uncorrected distance
      visual acuity of 0.00 logMAR (20/20) or better and 100% of eyes achieved
      corrected distance visual acuity of 0.00 logMAR (20/20) or better at most recent
      follow-up. CONCLUSIONS: Our study suggests that excellent visual outcomes can be
      achieved if an immediate lamellar recut is performed after suction loss with a
      femtosecond laser.

PMID- 22149664
TI  - Short-term cell death and inflammation after intracorneal inlay implantation in
      rabbits.
AB  - PURPOSE: To investigate the cell death and inflammatory response to insertion of
      the KAMRA inlay (AcuFocus Inc) for presbyopia. METHODS: Twenty-four rabbits were
      included in the study. Each rabbit had pockets generated in both corneas with a
      femtosecond laser. One eye of each rabbit had an inlay inserted into the pocket
      and the opposite control eye had the pocket dissected. Eight rabbits were studied
      at 24 hours, 48 hours, or 6 weeks after surgery. Tissue sections were analyzed
      with TUNEL assay to detect cell death and immunohistochemistry for CD11b to
      detect monocytes as a marker of inflammation. RESULTS: The inlay group had
      significantly more stromal cell death than the control group at 48 hours after
      surgery (P=.038). At 24 hours and 6 weeks after surgery, no significant
      difference was noted in stromal cell death between the inlay and control groups.
      Significantly more CD11b+ cells were noted in the stroma in the inlay group
      compared to the control group at 24 and 48 hours after surgery (P=.025 and
      P=.001, respectively). However, at 6 weeks after surgery, no significant
      difference in CD11b+ cells was observed between the control and inlay groups
      (P=.05). CONCLUSIONS: Although an early increase in stromal cell death and
      inflammation occurred in eyes that underwent femtosecond laser pocket creation
      and KAMRA inlay insertion compared to a control group with the pocket only, no
      significant difference was noted between the inlay and control groups in stromal
      cell death or inflammation at 6 weeks after surgery.

PMID- 22149665
TI  - Precision analysis of posterior corneal topography measured by Visante Omni:
      repeatability, reproducibility, and agreement with Orbscan II.
AB  - PURPOSE: To evaluate the repeatability and reproducibility of posterior corneal
      curvature and posterior corneal elevation best-fit sphere (BFS) obtained with the
      Visante Omni (Carl Zeiss Meditec) and to compare the results with the Orbscan II
      (Bausch & Lomb). METHODS: Thirty eyes from 30 healthy volunteers were included in
      this study. All patients were examined 5 times with the Visante Omni and Orbscan
      II by 2 independent operators. The posterior corneal curvature (3- and 6-mm zone)
      and posterior corneal elevation BFS (5- and 8-mm zone) were generated for each
      system. Intraoperator repeatability and interoperator reproducibility and
      agreement between the systems were evaluated using the intraclass correlation
      coefficient (ICC) and the Bland-Altman method. RESULTS: The repeatability of
      posterior corneal curvature and posterior corneal elevation BFS measured by the
      Visante Omni was high for all analysis zones (ICC, 0.99 to 1.00). The
      reproducibility also showed similar results (ICC, 0.99 to 1.00). Agreement
      between the Visante Omni and Orbscan II was high for posterior corneal curvature
      (ICC, 0.94 to 0.97) and posterior corneal elevation BFS (ICC, 0.96 to 0.98) with
      95% limits of agreement at -0.26 to 0.22 diopters for posterior corneal curvature
      and 0.11 to 0.69 mm for posterior corneal elevation BFS. CONCLUSIONS: The Visante
      Omni provides good repeatability and reproducibility of posterior corneal
      topography. Overall agreement with the Orbscan II system was high.

PMID- 22149666
TI  - Modification of polyurethane surface with an antithrombin-heparin complex for
      blood contact: influence of molecular weight of polyethylene oxide used as a
      linker/spacer.
AB  - Polyurethane (PU) was modified using isocyanate chemistry to graft polyethylene
      oxide (PEO) of various molecular weights (range 300-4600). An antithrombin
      heparin (ATH) covalent complex was subsequently attached to the free PEO chain
      ends, which had been functionalized with N-hydroxysuccinimide (NHS) groups.
      Surfaces were characterized by water contact angle and X-ray photoelectron
      spectroscopy (XPS) to confirm the modifications. Adsorption of fibrinogen from
      buffer was found to decrease by ~80% for the PEO-modified surfaces compared to
      the unmodified PU. The surfaces with ATH attached to the distal chain end of the
      grafted PEO were equally protein resistant, and when the data were normalized to
      the ATH surface density, PEO in the lower MW range showed greater protein
      resistance. Western blots of proteins eluted from the surfaces after plasma
      contact confirmed these trends. The uptake of ATH on the PEO-modified surfaces
      was greatest for the PEO of lower MW (300 and 600), and antithrombin binding from
      plasma (an indicator of heparin anticoagulant activity) was highest for these
      same surfaces. The PEO-ATH- and PEO-modified surfaces also showed low platelet
      adhesion from flowing whole blood. It is concluded that for the PEO-ATH surfaces,
      PEO in the low MW range, specifically MW 600, may be optimal for achieving an
      appropriate balance between resistance to nonspecific protein adsorption and the
      ability to take up ATH and bind antithrombin in subsequent blood contact.

PMID- 22149667
TI  - The impact of admission procalcitonin on prognosis in acute coronary syndromes: a
      pilot study.
AB  - BACKGROUND: Available evidence on the prognostic role of procalcitonin levels in
      acute coronary syndromes (ACS) is so far controversial. AIMS: To evaluate the
      association between procalcitonin, major cardiovascular events (MACE) and total
      mortality in acute coronary syndromes. METHODS: Procalcitonin levels were
      measured in 247 patients admitted to our Intensive Cardiac Care Unit (ICCU) with
      ACS. Three subgroups were considered according to procalcitonin levels. RESULTS:
      At Cox regression analysis, procalcitonin levels were both an unadjusted and an
      adjusted predictor (corrected for diagnosis and TnI) of intra-ICCU mortality and
      of 1-year follow-up MACE and total mortality. CONCLUSIONS: In ACS, admission
      procalcitonin values identify a "higher risk" group of patients for short and
      long-term mortality.

PMID- 22149668
TI  - Closing the loop between neuroscience and information technology: a possible
      mission?

PMID- 22149669
TI  - Could information theory provide an ecological theory of sensory processing?
AB  - The sensory pathways of animals are well adapted to processing a special class of
      signals, namely stimuli from the animal's environment. An important fact about
      natural stimuli is that they are typically very redundant and hence the sampled
      representation of these signals formed by the array of sensory cells is
      inefficient. One could argue for some animals and pathways, as we do in this
      review, that efficiency of information representation in the nervous system has
      several evolutionary advantages. Consequently, one might expect that much of the
      processing in the early levels of these sensory pathways could be dedicated
      towards recoding incoming signals into a more efficient form. In this review, we
      explore the principle of efficiency of information representation as a design
      principle for sensory processing. We give a preliminary discussion on how this
      principle could be applied in general to predict neural processing and then
      discuss concretely some neural systems where it recently has been shown to be
      successful. In particular, we examine the fly's LMC coding strategy and the
      mammalian retinal coding in the spatial, temporal and chromatic domains.

PMID- 22149670
TI  - A unified description of cerebellar inter-spike interval distributions and
      variabilities using summation of Gaussians.
AB  - Neuronal inter-spike intervals (ISIs) have previously been described as Poisson,
      Gamma, inverse Gaussian or other unimodal distributions. We analyzed ISIs of
      rhythmic and arrhythmic neuronal spike trains in cerebellum recorded from freely
      behaving rats, and found that their distributions can be described as the
      summation or integration of multiple Gaussian distributions. The ISIs of rhythmic
      cerebellar Purkinje cells have a main Gaussian peak at a basic firing interval
      and exponentially reduced peaks at multiples of this firing period. ISIs of
      arrhythmic Purkinje cells can be modeled as the integration of multiple Gaussian
      distributions centered at continuous intervals with exponentially reduced peak
      amplitudes. The sources of variability are directly related to the relative
      timing of action potentials between neighboring cells since we show that
      irregularities of discharge in one cell are associated with the previous history
      of its discharge in time relative to another cell. Through relative phase
      analyses, we demonstrate that the shape and the mathematical form of the ISI
      distributions in cerebellum are direct result of dynamic interactions in the
      nearby neuronal network, in addition to intrinsic firing properties. The analysis
      in this paper provides a unified description of cerebellar inter-spike interval
      distributions which deviate from the usual Poisson assumptions. Our results
      suggest the existence of an intrinsic rhythmicity in cells exhibiting arrhythmic
      spike trains in cerebellum, and may identify an important source of variability
      in neuronal firing patterns that is relevant to the mechanism of neural
      computation in cerebellum.

PMID- 22149671
TI  - On nonlinearity in neural encoding models applied to the primary visual cortex.
AB  - Within the regression framework, we show how different levels of nonlinearity
      influence the instantaneous firing rate prediction of single neurons.
      Nonlinearity can be achieved in several ways. In particular, we can enrich the
      predictor set with basis expansions of the input variables (enlarging the number
      of inputs) or train a simple but different model for each area of the data
      domain. Spline-based models are popular within the first category. Kernel
      smoothing methods fall into the second category. Whereas the first choice is
      useful for globally characterizing complex functions, the second is very handy
      for temporal data and is able to include inner-state subject variations. Also,
      interactions among stimuli are considered. We compare state-of-the-art firing
      rate prediction methods with some more sophisticated spline-based nonlinear
      methods: multivariate adaptive regression splines and sparse additive models. We
      also study the impact of kernel smoothing. Finally, we explore the combination of
      various local models in an incremental learning procedure. Our goal is to
      demonstrate that appropriate nonlinearity treatment can greatly improve the
      results. We test our hypothesis on both synthetic data and real neuronal
      recordings in cat primary visual cortex, giving a plausible explanation of the
      results from a biological perspective.

PMID- 22149672
TI  - A trick for computing expected values in high-dimensional probabilistic models.
AB  - Sensory stimuli are generally encoded by the activity of thousands of neurons in
      parallel. Coding theories dealing with such high-dimensional representations face
      hard numerical problems. One of them is the computation of expected values
      according to the underlying probability distributions. Direct computations are
      generally avoided also because of the high numerical precision required. Here, a
      numerical trick is described that overcomes the problem of numerical precision,
      thereby providing a simple alternative to indirect methods based on stochastic
      sampling (Monte-Carlo methods).

PMID- 22149673
TI  - A general mathematical model of transduction events in mechano-sensory stretch
      receptors.
AB  - Crayfish (Astacus astacus) muscle stretch receptors show strong homology to
      mammalian muscle spindles and bipolar neurons in D. melanogaster. All are
      typical, non-ciliated, stretch-sensitive, afferent neurons. Such receptors are
      observed in many species and perform an important sensory role. However, they are
      poorly characterised. A previous study reported a bio-mechanical and behavioural
      model of A. astacus stretch receptors, which used the principles of elasticity
      and tension in a spring to describe the adaptation of a mechano-sensory ending.
      This model described the changing mechano-sensory currents in the receptor when
      subjected to a stretch protocol. Here, we re-implement and extend this model.
      Notably, we introduce additional descriptions of voltage-gated channels that are
      suggested to contribute to stretch receptor mechano-transduction. Our model
      presents a more complete picture of the initiation of the mechano-receptor
      potential in response to a stretching stimulus. The inclusion of voltage
      dependent sodium and potassium currents in addition to the initial mechano
      sensitive sodium current allowed the model to account for most of the initial
      stretch response of the receptor. This preliminary model has potential for
      extension to describe fully the behaviour of non-ciliated mechano-sensors across
      species and predict the molecular mediators of mechano-transduction.

PMID- 22149674
TI  - Evolution and development of brain networks: from Caenorhabditis elegans to Homo
      sapiens.
AB  - Neural networks show a progressive increase in complexity during the time course
      of evolution. From diffuse nerve nets in Cnidaria to modular, hierarchical
      systems in macaque and humans, there is a gradual shift from simple processes
      involving a limited amount of tasks and modalities to complex functional and
      behavioral processing integrating different kinds of information from highly
      specialized tissue. However, studies in a range of species suggest that
      fundamental similarities, in spatial and topological features as well as in
      developmental mechanisms for network formation, are retained across evolution.
      'Small-world' topology and highly connected regions (hubs) are prevalent across
      the evolutionary scale, ensuring efficient processing and resilience to internal
      (e.g. lesions) and external (e.g. environment) changes. Furthermore, in most
      species, even the establishment of hubs, long-range connections linking distant
      components, and a modular organization, relies on similar mechanisms. In
      conclusion, evolutionary divergence leads to greater complexity while following
      essential developmental constraints.

PMID- 22149675
TI  - The challenge of non-ergodicity in network neuroscience.
AB  - Ergodicity can be assumed when the structure of data is consistent across
      individuals and time. Neural network approaches do not frequently test for
      ergodicity in data which holds important consequences for data integration and
      intepretation. To demonstrate this problem, we present several network models in
      healthy and clinical samples where there exists considerable heterogeneity across
      individuals. We offer suggestions for the analysis, interpretation, and reporting
      of neural network data. The goal is to arrive at an understanding of the sources
      of non-ergodicity and approaches for valid network modeling in neuroscience.

PMID- 22149676
TI  - Oligomerization preceding amyloid fibril formation: a process in common to
      intrinsically disordered and globular proteins.
AB  - Neurodegenerative diseases present a big burden to society. At the molecular
      level many of them - if not all - show protein aggregation (as an epiphenomenon
      or as a cause). The knowledge on details of thermodynamics and kinetics as well
      as structure of the protein aggregates, especially the early and soluble
      oligomers, may help in designing inhibitors for early stages of such diseases.
      Here, a possible outlook on more general mechanism for their formation is
      discussed. The oligomers of amyloid forming proteins, which are present prior and
      during nucleation and amyloid fibril formation, are claimed to be toxic to cells.
      Oligomers of the globular proteins and the intrinsically disordered proteins
      (IDPs), form in vitro upon partial denaturation and renaturation, respectively.
      Often they form if the sample is heated or freeze-thawed for a few cycles. A
      question is asked if this does not highlight one important property in common to
      globular proteins and IDPs, namely, a high energetic barrier dividing such
      oligomers from the monomers. This also would imply existence of two populations
      of states, one, the monomer - being metastable - at least under the conditions,
      which promote fibril formation.

PMID- 22149677
TI  - Neurobiological correlates of imaging.

PMID- 22149678
TI  - Alzheimer's disease.

PMID- 22149680
TI  - Artificial neural networks: an overview.

PMID- 22149679
TI  - Deep brain stimulation: anatomical, physiological, and computational mechanisms.

PMID- 22149681
TI  - What autoassociative network models may tell us about the neurobiology of memory.

PMID- 22149682
TI  - An overview of population genetic data simulation.
AB  - Simulation studies in population genetics play an important role in helping to
      better understand the impact of various evolutionary and demographic scenarios on
      sequence variation and sequence patterns, and they also permit investigators to
      better assess and design analytical methods in the study of disease-associated
      genetic factors. To facilitate these studies, it is imperative to develop
      simulators with the capability to accurately generate complex genomic data under
      various genetic models. Currently, a number of efficient simulation software
      packages for large-scale genomic data are available, and new simulation programs
      with more sophisticated capabilities and features continue to emerge. In this
      article, we review the three basic simulation frameworks--coalescent, forward,
      and resampling--and some of the existing simulators that fall under these
      frameworks, comparing them with respect to their evolutionary and demographic
      scenarios, their computational complexity, and their specific applications.
      Additionally, we address some limitations in current simulation algorithms and
      discuss future challenges in the development of more powerful simulation tools.

PMID- 22149683
TI  - Population model-based inter-diplotype similarity measure for accurate diplotype
      clustering.
AB  - Classification of the individuals' genotype data is important in various kinds of
      biomedical research. There are many sophisticated clustering algorithms, but most
      of them require some appropriate similarity measure between objects to be
      clustered. Hence, accurate inter-diplotype similarity measures are always
      required for classification of diplotypes. In this article, we propose a new
      accurate inter-diplotype similarity measure that we call the population model
      based distance (PMD), so that we can cluster individuals with diplotype SNPs data
      (i.e., unphased-diplotypes) with higher accuracies. For unphased-diplotypes, the
      allele sharing distance (ASD) has been the standard to measure the genetic
      distance between the diplotypes of individuals. To achieve higher clustering
      accuracies, our new measure PMD makes good use of a given appropriate population
      model which has never been utilized in the ASD. As the population model, we
      propose to use an hidden Markov model (HMM)-based model. We call the PMD based on
      the model the HHD (HIT HMM-based Distance). We demonstrate the impact of the HHD
      on the diplotype classification through comprehensive large-scale experiments
      over the genome-wide 8930 data sets derived from the HapMap SNPs database. The
      experiments revealed that the HHD enables significantly more accurate clustering
      than the ASD.

PMID- 22149684
TI  - Optimization of hepatocarcinoma uptake with radiolabeled lipiodol: development of
      new lipiodol formulations with increased viscosity.
AB  - The aim of this study was to develop new Lipiodol formulations with increased
      viscosities to augment Lipiodol embolic effect and optimize efficiency of
      radiolabeled Lipiodol in hepatocarcinoma treatments. New Lipiodol formulations
      consist of Lipiodol mixtures with different stearic acid concentrations (0.8%,
      1.3%, and 1.8%). These formulations were fully characterized in vitro (viscosity,
      rheologic profiles) and labeled with 99mTc. Their viscosities at 20 degrees C are
      54, 60, and 67cP respectively, versus 45cP for Lipiodol ultra-fluide. Second,
      their biodistribution profiles were studied in vivo, at 24 and 72 hours, in
      hepatoma-bearing rats, and compared to control group (99mTc-Lipiodol).
      Biodistribution at 24 hours show a Gaussian tumor uptake profile with a maximum
      obtained with 1.3% stearic acid, and a tumor uptake superior to control group
      (+67%) (p<0.05). At 72 hours, optimal tumor uptake is reached with the 0.8%
      formulation, with 89% increase compared with control group (p<0.05). Moreover, we
      show a tendency to the decrease of pulmonary uptake for the new formulations at
      24 hours and 72 hours. These results suggest a correlation between viscosity and
      Lipiodol tumor uptake. The new 0.8% stearic acid/Lipiodol formulation appears to
      be the optimized formulation for Lipiodol treatments of hepatocarcinoma, since it
      leads to a significant increase of tumor uptake at 72 hours and possibly to a
      decrease of undesirable pulmonary effects.

PMID- 22149685
TI  - Whole-body distribution and radiation dosimetry of (68)Ga-NOTA-RGD, a positron
      emission tomography agent for angiogenesis imaging.
AB  - (68)Ga labeled NOTA-RGD was a recently developed positron emission tomography
      (PET) radiotracer for the visualization of angiogenesis, and is regarded as a
      promising imaging agent for cancer and several other disorders. In this study, we
      investigated the whole-body distribution and radiation dosimetry of (68)Ga-NOTA
      RGD in humans. Ten cancer patients (53.7 +/- 13.5 years; 61.5 +/- 7.4  kg)
      participated in this study. PET scans were performed using a PET/computed
      tomography (scanner in three-dimensional mode). After an intravenous injection of
      172.4 +/- 20.5  MBq of (68)Ga-NOTA-RGD, eight serial whole-body scans were
      performed during 90 minutes. Volumes of interest were drawn manually over the
      entire volumes of the urinary bladder, the gallbladder, heart, kidneys, liver,
      lungs, pancreas, spleen, and stomach. Time-activity curves were obtained from
      serial PET scan data. Residence times were calculated from areas under curve of
      time-activity curves and used as input to the OLINDA/EXM 1.1 software. The uptake
      of (68)Ga-NOTA-RGD was highest in the kidneys and urinary bladder. Radiation
      doses to kidneys and urinary bladder were 71.6 +/- 28.4  MU Gy/MBq and 239.6 +/-
      56.6  MU Gy/MBq. Mean effective doses were 25.0 +/- 4.4  MU Sv/MBq using
      International Commission of Radiation Protection (ICRP) publication 60 and 22.4
      +/- 3.8  MU Sv/MBq using ICRP publication 103 weighting factor. We evaluated the
      radiation dosimetry of (68)Ga labeled NOTA-RGD, which has an acceptable effective
      radiation dose.

PMID- 22149693
TI  - Attributing illness to 'old age:' consequences of a self-directed stereotype for
      health and mortality.
AB  - Stereotypic beliefs about older adults and the aging process have led to
      endorsement of the myth that 'to be old is to be ill.' This study examined
      community-dwelling older adults' (N = 105, age 80+) beliefs about the causes of
      their chronic illness (ie, heart disease, cancer, diabetes, etc.), and tested the
      hypothesis that attributing the onset of illness to 'old age' is associated with
      negative health outcomes. A series of multiple regressions (controlling for
      chronological age, gender, income, severity of chronic conditions, functional
      status and health locus of control) demonstrated that 'old age' attributions were
      associated with more frequent perceived health symptoms, poorer health
      maintenance behaviours and a greater likelihood of mortality at 2-year follow-up.
      The probability of death was more than double among participants who strongly
      endorsed the 'old age' attribution as compared to those who did not (36% vs.
      14%). Findings are framed in the context of self-directed stereotypes and
      implications for potential interventions are considered.

PMID- 22149694
TI  - Can the partial deletion in the Y chromosome of male mice affect the reproductive
      efficiency of their daughters?
AB  - It has been previously shown that cumuli oophori around ovulated oocytes of
      B10.BR-Y(del) female mice (sired by males with the deleted Y chromosome) are more
      resistant to enzymatic treatment than cumuli oophori around eggs of control
      B10.BR females (having fathers with the intact Y chromosome). This can imply that
      some genes which influence the establishment of the imprinting pattern in male
      gametes are located in the region covered by the deletion. We hypothesize that
      the Y-dependent imprinting pattern, inherited by female offspring, affects
      stability of periovum layers within them. In the present study, cumulus-oocyte
      complexes ovulated by females from consomic strains: DBA, DBA-Y(BR), DBA-Y(del),
      and CBA, CBA-Y(BR), CBA-Y(del) were tested for their susceptibility to
      hyaluronidase digestion. The mean times for dispersal of cumulus cells
      surrounding oocytes of females from the backcross lines were convergent with the
      times typical for oocytes from strains being the donors of the Y chromosome
      (B10.BR or B10.BR-Y(del)) and differed clearly from pure DBA and CBA strains. It
      confirmed previous findings that Y chromosomes of fathers influence the
      properties of cumulus-oocyte complexes ovulated by their daughters. This
      influence is definitely stronger than the influence of the genetic background.
      Additionally, it was demonstrated that the cumuli oophori surrounding oocytes of
      B10.BR-Y(del) females exhibit increased resistance to penetration by spermatozoa
      in vitro, in comparison to the control B10.BR strain. This regularity was
      reflected in the decreased proportion of fertilized ova recovered from oviducts
      of B10.BR-Y(del) females mated with B10.BR-Y(del) males and in the lower litter
      sizes recorded for these pairs. The excessive stability of cumuli oophori typical
      for oocytes of females having Y(del) fathers may negatively affect their
      fertility, if they have partners producing poor quality sperm.

PMID- 22149695
TI  - The role of ecological dynamics in analysing performance in team sports.
AB  - Performance analysis is a subdiscipline of sports sciences and one-approach,
      notational analysis, has been used to objectively audit and describe behaviours
      of performers during different subphases of play, providing additional
      information for practitioners to improve future sports performance. Recent
      criticisms of these methods have suggested the need for a sound theoretical
      rationale to explain performance behaviours, not just describe them. The aim of
      this article was to show how ecological dynamics provides a valid theoretical
      explanation of performance in team sports by explaining the formation of
      successful and unsuccessful patterns of play, based on symmetry-breaking
      processes emerging from functional interactions between players and the
      performance environment. We offer the view that ecological dynamics is an upgrade
      to more operational methods of performance analysis that merely document
      statistics of competitive performance. In support of our arguments, we refer to
      exemplar data on competitive performance in team sports that have revealed
      functional interpersonal interactions between attackers and defenders, based on
      variations in the spatial positioning of performers relative to each other in
      critical performance areas, such as the scoring zones. Implications of this
      perspective are also considered for practice task design and sport development
      programmes.

PMID- 22149696
TI  - Efficacy of nonsurgical interventions for anterior knee pain: systematic review
      and meta-analysis of randomized trials.
AB  - Anterior knee pain is a chronic condition that presents frequently to sports
      medicine clinics, and can have a long-term impact on participation in physical
      activity. Conceivably, effective early management may prevent chronicity and
      facilitate physical activity. Although a variety of nonsurgical interventions
      have been advocated, previous systematic reviews have consistently been unable to
      reach conclusions to support their use. Considering a decade has lapsed since
      publication of the most recent data in these reviews, it is timely to provide an
      updated synthesis of the literature to assist sports medicine practitioners in
      making informed, evidence-based decisions. A systematic review and meta-analysis
      was conducted to evaluate the evidence for nonsurgical interventions for anterior
      knee pain. A comprehensive search strategy was used to search MEDLINE, EMBASE,
      CINAHL and Pre-CINAHL, PEDro, PubMed, SportDiscus, Web of Science, BIOSIS
      Previews, and the full Cochrane Library, while reference lists of included papers
      and previous systematic reviews were hand searched. Studies were eligible for
      inclusion if they were randomized clinical trials that used a measure of pain to
      evaluate at least one nonsurgical intervention over at least 2 weeks in
      participants with anterior knee pain. A modified version of the PEDro scale was
      used to rate methodological quality and risk of bias. Effect size calculation and
      meta-analyses were based on random effects models. Of 48 suitable studies, 27
      studies with low-to-moderate risk of bias were included. There was minimal
      opportunity for meta-analysis because of heterogeneity of interventions,
      comparators and follow-up times. Meta-analysis of high-quality clinical trials
      supports the use of a 6-week multimodal physiotherapy programme (standardized
      mean difference [SMD] 1.08, 95% CI 0.73, 1.43), but does not support the addition
      of electromyography biofeedback to an exercise programme in the short-term (4
      weeks: SMD -0.21, 95% CI -0.64, 0.21; 8-12 weeks: SMD -0.22, 95% CI -0.65, 0.20).
      Individual study data showed beneficial effects for foot orthoses with and
      without multimodal physiotherapy (vs flat inserts), exercise (vs control), closed
      chain exercises (vs open chain exercises), patella taping in conjunction with
      exercise (vs exercise alone) and acupuncture (vs control). Findings suggest that,
      in implementing evidence-based practice for the nonsurgical management of
      anterior knee pain, sports medicine practitioners should prescribe local,
      proximal and distal components of multimodal physiotherapy in the first instance
      for suitable patients, and then consider foot orthoses or acupuncture as
      required.

PMID- 22149698
TI  - Polyisocyanides as a new alignment medium to measure residual dipolar couplings
      for small organic molecules.
AB  - Polyisocycanides were found to give anisotropic molecular alignment in the
      magnetic field and are useful to measure residual dipolar couplings (RDCs) from
      analytes, e.g. strychnine. They show less quadrupolar splitting of the deuterated
      solvent signal compared with other liquid crystal systems such as Poly-gamma
      benzyl-L-glutamate (PBLG) and hence less undesired line broadening.

PMID- 22149697
TI  - Evaluation and treatment of disorders of the infrapatellar fat pad.
AB  - The infrapatellar fat pad (IFP), also known as Hoffa's fat pad, is an
      intracapsular, extrasynovial structure that fills the anterior knee compartment,
      and is richly vascularized and innervated. Its degree of innervation, the
      proportion of substance-P-containing fibres and close relationship to its
      posterior synovial lining implicates IFP pathologies as a source of infrapatellar
      knee pain. Though the precise function of the IFP is unknown, studies have shown
      that it may play a role in the biomechanics of the knee or act as a store for
      reparative cells after injury. Inflammation and fibrosis within the IFP, caused
      by trauma and/or surgery can lead to a variety of arthrofibrotic lesions
      including Hoffa's disease, anterior interval scarring and infrapatellar
      contracture syndrome. Lesions or mass-like abnormalities rarely occur within the
      IFP, but their classification can be narrowed down by radiographical appearance.
      Clinically, patients with IFP pathology present with burning or aching
      infrapatellar anterior knee pain that can often be reproduced on physical exam
      with manoeuvres designed to produce impingement. Sagittal MRI is the most common
      imaging technique used to assess IFP pathology including fibrosis, inflammation,
      oedema, and mass-like lesions. IFP pathology is often successfully managed with
      physical therapy. Passive taping is used to unload or shorten an inflamed IFP,
      and closed chain quadriceps exercises can improve lower limb control and patellar
      congruence. Training of the gluteus medius and stretching the anterior hip may
      help to decrease internal rotation of the hip and valgus force at the knee. Gait
      training and avoiding hyperextension can also be used for long-term management.
      Injections within the IFP of local anaesthetic plus corticosteroids and IFP
      ablation with ultrasound guided alcohol injections have been successfully
      explored as treatments for IFP pain. IFP pathology refractory to physical therapy
      can be approached through a variety of operative treatments. Arthroscopic partial
      resection for IFP impingement and Hoffa's disease has showed favourable results;
      however, total excision of the IFP performed concomitantly with total knee
      arthroplasty (TKA) resulted in worse results when compared with TKA alone.
      Arthroscopic debridement of IFP fibrosis has been successfully used to treat
      extension block following anterior cruciate ligament reconstruction, and
      arthroscopic anterior interval release has been an effective treatment for pain
      associated with anterior interval scarring. Arthroscopic resection of
      infrapatellar plicae and denervation of the inferior pole of the patella have
      also been shown to be effective treatments for refractory infrapatellar pain.

PMID- 22149699
TI  - Integrating social and biomedical science in HIV vaccine research: obstacles,
      opportunities and ways forward.

PMID- 22149700
TI  - The role of risk analysis in polio eradication: modeling possibilities,
      probabilities and outcomes to inform choices.

PMID- 22149701
TI  - The challenge of improving immunization coverage: the New Zealand example.

PMID- 22149703
TI  - Fluzone((r)) Intradermal vaccine: a promising new chance to increase the
      acceptability of influenza vaccination in adults.
AB  - On May 9 2011, the US FDA approved Sanofi Pasteur's Fluzone((r)) Intradermal
      influenza vaccine, the first influenza vaccine licensed in the USA that uses a
      new microinjection system for intradermal delivery of vaccines (SoluviaTM, Becton
      Dickinson). Its antigen content is lower (9 ug hemagglutinin per strain) than the
      conventional intramuscular vaccine (15 ug) and it is indicated for active
      immunization of adults aged between 18 and 64 years. Data from the clinical trial
      assessing immunogenicity and safety of Fluzone Intradermal in adults were
      consistent with substantial experience accumulated with Intanza((r)) 9 ug, the
      intradermal vaccine licensed on February 26 2009 and launched during the
      2010/2011 season in Europe. Fluzone Intradermal is safe and its immunogenicity
      comparable with that of conventional intramuscular vaccines. Obtaining optimal
      acceptability of intradermal vaccines may represent an additional asset to help
      increase the coverage of influenza vaccination in young adults.

PMID- 22149704
TI  - Advancing vaccinology in India.
AB  - India's inaugural Advanced Vaccinology Course, hosted by the Child Health
      Foundation and the International Clinical Epidemiology Network, attracted
      approximately 55 EPI managers and privately-practicing physicians from across the
      country. The comprehensive course provided training in epidemiology, disease
      surveillance, and vaccine safety and regulation. Core lectures highlighted
      vaccination trends, challenges, and innovations specific to India; 'Breakout
      Sessions' and the 'State-of-the-Art Lecture Series' complemented core course
      material. Overall, the course aimed to provide an advanced education in classic
      and topical areas of vaccinology to ensure that India has the tools and skills
      required to safely manage and grow its national immunization program.

PMID- 22149705
TI  - First clinical trial of purified, irradiated malaria sporozoites in humans.
AB  - Purified, irradiated, metabolically active sporozoites of Plasmodium falciparum
      (PfSPZ) have been administered to 80 volunteers through subcutaneous or
      intradermal routes. This PfSPZ vaccine has been shown to be safe but of low
      immunogenicity and hence protective efficacy as shown after challenge with
      infected mosquitoes. Intravenous delivery of PfSPZ in nonhuman primates induced
      memory CD8(+) and CD4(+) T cells specific for PfSPZ that reside in the liver.
      Further studies using PfSPZ and the intravenous route in humans are warranted to
      fully explore the potential of purified, attenuated sporozoites for malaria
      vaccine development.

PMID- 22149706
TI  - A novel genetically engineered Mycobacterium smegmatis-based vaccine promotes
      anti-TB immunity.
AB  - Pulmonary TB remains a global health threat. Prophylactic immunization with
      Mycobacterium bovis BCG is the only key strategy to control TB. Ineffectiveness
      of BCG immunization in TB-endemic areas and BCG-related safety issues in HIV
      positive infants have prompted the development of new TB vaccines. As enhanced
      understanding of the immune evasion mechanism of Mycobacterium tuberculosis will
      help develop new vaccines, Sweeney et al. studied the role of the esx-3 locus in
      mycobacterial pathogenesis. They have identified a previously unappreciated
      function of the esx-3 locus in innate immune evasion. They further discovered
      that Mycobacterium smegmatis with the esx-3 genes deleted could function as a
      novel vaccine vector with an enhanced innate immune-activating property. This
      vector, when engineered to express M. tuberculosis esx-3, was found to be a
      potent TB vaccine capable of a level of protection superior to that of BCG when
      administered via the intravenous route.

PMID- 22149708
TI  - Predictions versus high-throughput experiments in T-cell epitope discovery:
      competition or synergy?
AB  - Prediction methods as well as experimental methods for T-cell epitope discovery
      have developed significantly in recent years. High-throughput experimental
      methods have made it possible to perform full-length protein scans for epitopes
      restricted to a limited number of MHC alleles. The high costs and limitations
      regarding the number of proteins and MHC alleles that are feasibly handled by
      such experimental methods have made in silico prediction models of high interest.
      MHC binding prediction methods are today of a very high quality and can predict
      MHC binding peptides with high accuracy. This is possible for a large range of
      MHC alleles and relevant length of binding peptides. The predictions can easily
      be performed for complete proteomes of any size. Prediction methods are still,
      however, dependent on good experimental methods for validation, and should merely
      be used as a guide for rational epitope discovery. We expect prediction methods
      as well as experimental validation methods to continue to develop and that we
      will soon see clinical trials of products whose development has been guided by
      prediction methods.

PMID- 22149709
TI  - mRNA vaccination as a safe approach for specific protection from type I allergy.
AB  - Allergic diseases are on the increase and current therapies are lacking in
      efficacy and patient compliance. In recent years, the idea of prophylactic
      measures, especially for children at high risk for allergy, has become
      increasingly popular. This review summarizes the available preclinical data for
      protective allergy vaccines, with a focus on one of the most promising vaccine
      candidates; mRNA vaccines. Recently, mRNA vaccines have been rediscovered as an
      alternative to their more prominent counterparts, the DNA vaccines. Allergen
      encoding mRNA vaccines elicit long-lasting protection from sensitization, and
      induce a type of immunity similar to the natural protective response that is
      acquired in the presence of microbial burden early in life. Owing to their
      excellent safety profile, they represent the ideal candidates for a vaccine that
      aims to protect at-risk children who have not yet been sensitized to allergens.

PMID- 22149710
TI  - Leishmaniasis: focus on the design of nanoparticulate vaccine delivery systems.
AB  - Although mass vaccination of the entire population of an endemic area would be
      the most cost-effective tool to diminish Leishmania burden, an effective vaccine
      is not yet commercially available. Practically, vaccines have failed to achieve
      the required level of protection, possibly owing to the lack of an appropriate
      adjuvant and/or delivery system. Therefore, there is still an imperative demand
      for an improved, safe and efficient delivery system to enhance the immunogenicity
      of available vaccine candidates. Nanoparticles are proficient in boosting the
      quality and magnitude of immune responses in a predictable fashion. Herein, we
      discuss how nanoparticulate vaccine delivery systems can be used to induce
      appropriate immune responses against leishmaniasis by controlling physicochemical
      properties of the vaccine. Stability, production reproducibility, low cost per
      dose and low risk-benefit ratios are desirable characteristics of an ideal
      vaccine formulation and solid lipid nanoparticles may serve as one of the most
      promising practical strategies to help to achieve such a leishmanial vaccine, at
      least in canine species in the developing world.

PMID- 22149711
TI  - Acellular vaccines for ovine brucellosis: a safer alternative against a worldwide
      disease.
AB  - Ovine brucellosis is a very contagious zoonotic disease distributed worldwide and
      constitutes a very important zoosanitary and economic problem. The control of the
      disease includes animal vaccination and slaughter of infected flocks. However,
      the commercially available vaccine in most countries is based on the attenuated
      strain Brucella melitensis Rev 1, which presents important safety drawbacks. This
      review is focused on the most recent and promising acellular vaccine proposals.

PMID- 22149712
TI  - Bacterial ghosts as carriers of protein subunit and DNA-encoded antigens for
      vaccine applications.
AB  - Bacterial ghosts (BGs) represent vaccine delivery systems gifted with outstanding
      natural adjuvant properties. BGs are empty cell envelopes of Gram-negative
      bacteria lacking cytoplasmic content yet retaining all unaltered morphological
      and structural features of their living counterparts. The intact surface make-up
      of BGs is easily recognized by professional APCs through pattern-recognition
      receptors, making them ideal for mucosal administration through oral, ocular,
      intranasal or aerogenic routes, which represent the most desirable methods of
      application in advanced vaccine use. BGs have been designed to be used as
      carriers of active substances and foreign antigens (protein and/or DNA) for
      vaccine development. This review highlights the salient features of the BGs'
      versatile multipurpose vaccine platform for application in a wide range of human
      and veterinary medicines.

PMID- 22149714
TI  - Fine mapping of the yellow seed locus in Brassica juncea L.
AB  - The yellow mustard plant in Northern Shaanxi is a precious germplasm, and the
      yellow seed trait is controlled by a single recessive gene. In this report,
      amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR)
      techniques were used to identify markers linked to the brown seed locus in an
      F(2) population consisting of 1258 plants. After screening 256 AFLP primer
      combinations and 456 pairs of SSR primers, we found 14 AFLP and 2 SSR markers
      that were closely linked to the brown seed locus. Among these markers, the SSR
      marker CB1022 showed codominant inheritance. By integrating markers previously
      found to be linked to the brown seed locus into the genetic map of the F(2)
      population, 23 markers were linked to the brown seed locus. The two closest
      markers, EA02MC08 and P03MC08, were located on either side of the brown seed
      locus at a distance of 0.3 and 0.5 cM, respectively. To use the markers for the
      breeding of yellow-seeded mustard plants, two AFLP markers (EA06MC11 and
      EA08MC13) were converted into sequence-characterized amplified region (SCAR)
      markers, SC1 and SC2, with the latter as the codominant marker. The two SSR
      markers were subsequently mapped to the A9/N9 linkage group of  Brassica napus 
      L. by comparing common SSR markers with the published genetic map of B. napus. A
      BLAST analysis indicated that the sequences of seven markers showed good
      colinearity with those of Arabidopsis chromosome 3 and that the homolog of the
      brown seed locus might exist between At3g14120 and At3g29615 on this same
      chromosome. To develop closer markers, we could make use of the sequence
      information of this region to design primers for future studies. Regardless, the
      close markers obtained in the present study will lay a solid foundation for
      cloning the yellow seed gene using a map-based cloning strategy.

PMID- 22149715
TI  - Post-polio syndrome: impact of hope on quality of life.
AB  - PURPOSE: To determine the effect of future-oriented coping strategies on the
      quality of life (QOL) of individuals with post-polio syndrome (PPS). METHODS: A
      correlative study, in which a cohort of 61 patients was surveyed and a group of
      40 healthy, age-matched individuals served as controls. Patients were surveyed as
      to their QOL, levels of hope and utilization of proactive coping, employment
      status and degree of functionality. RESULTS: PPS patients had lower total,
      physical and mental QOL indices compared to controls. Future-oriented coping
      strategies associated with hope were positively associated with physical and
      mental QOL in the PPS group, but not in the controls. In a multivariate analysis,
      hope and employment status predicted higher QOL among those with PPS.
      CONCLUSIONS: Future-oriented coping strategies, particularly hope are
      distinctively associated with improved QOL benefits in PPS patients. Fostering
      future-oriented coping related to hope may improve the self-perceived mental and
      physical status of patients with PPS.

PMID- 22149717
TI  - Fusogenic activity of PEGylated pH-sensitive liposomes.
AB  - The aim of this study was to investigate the fusogenic properties of
      poly(ethylene glycol) (PEG)ylated dioleoylphosphatidylethanolamine/cholesteryl
      hemisuccinate (DOPE/CHEMS) liposomes. These pH-sensitive liposomes were prepared
      by incorporating two different PEG lipids: distearoylphosphatidylethanolamine
      (DSPE)-PEG2000 was mixed with the liposomal lipids using the conventional method,
      whereas sterol-PEG1100 was inserted into the outer monolayer of preformed
      vesicles. Both types of PEGylated liposomes were characterized and compared for
      their entrapment efficiency, zeta potential and size, and were tested in vitro
      for pH sensitivity by means of proton-induced leakage and membrane fusion
      activity. To mimic the routes of intracellular delivery, fusion between pH
      sensitive liposomes and liposomes designed to simulate the endosomal membrane was
      studied. Our investigations confirmed that DOPE/CHEMS liposomes were capable of
      rapidly releasing calcein and of fusing upon acidification. However, after
      incorporation of DSPE-PEG2000 or sterol-PEG1100 into the membrane, pH sensitivity
      was significantly reduced; as the mol ratio of PEG-lipid was increased, the
      ability to fuse was decreased. Comparison between two different PEGylated pH
      sensitive liposomes showed that only vesicles containing 0.6 mol% sterol-PEG1100
      in the outer monolayer were still capable of fusing with the endosome-like
      liposomes and showing leakage of calcein at pH 5.5.

PMID- 22149716
TI  - Immunomodulation using agonists and antagonists: potential clinical applications.
AB  - INTRODUCTION: Extensive studies have gone into understanding the differential
      role of the innate and adaptive arms of the immune system in the context of
      various diseases. Receptor-ligand interactions are responsible for mediating
      cross-talk between the innate and adaptive arms of the immune system, so as to
      effectively counter the pathogenic challenge. While TLRs remain the best studied
      innate immune receptor, many other receptor families are now coming to the fore
      for their role in various pathologies. Research has focused on the discovery of
      novel agonists and antagonists for these receptors as potential therapeutics.
      AREAS COVERED: In this review, we present an overview of the recent advances in
      the discovery of drugs targeting important receptors such as G-protein coupled
      receptors, TRAIL-R, IL-1beta receptor, PPARs, etc. All these receptors play a
      critical role in the modulation of the immune response. We focus on the recent
      paradigms applied for the generation of specific and effective therapeutics for
      these receptors and their status in clinical trials. EXPERT OPINION: Non-specific
      activation by antagonist/agonist is a difficult problem to dodge. This demands
      innovation in ligand designing with the use of strategies such as allosterism and
      dual-specific ligands. Rigorous preclinical and clinical studies are required in
      transforming a compound to a therapeutic.

PMID- 22149718
TI  - Estimating glomerular filtration rate in hypertensive subjects: comparison of the
      chronic kidney disease epidemiology collaboration (CKD-EPI) and modification of
      diet in renal disease (MDRD) study equations.
AB  - BACKGROUND: The Modification of Diet in Renal Disease (MDRD) Study equation is
      the most commonly used formula for estimation of glomerular filtration rate
      (eGFR). Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      developed a new equation to provide a more accurate estimate of GFR among
      individuals with normal or mildly reduced renal function. AIM: To compare the
      MDRD and CKD-EPI equations in hypertensive population treated in general
      practice. METHODS: The MDRD and CKD-EPI equations were applied to a cohort of 994
      hypertensive subjects aged 45-70 years without cardiovascular or renal disease or
      previously known diabetes. RESULTS: The prevalence of CKD stage 3 (eGFR 30-59
      mL/min per 1.73 m(2)) was 6.7% (95% CI 5.3-8.5) (67/994) according to the MDRD
      formula and 3.7% (95% CI 2.6-5.1) (37/994) according to the CKD-EPI formula. Of
      the 67 subjects classified as having CKD stage 3 according to the MDRD equation,
      30 (44.8%) were reclassified as 'no-CKD' by the CKD-EPI equation. These subjects
      were mostly women 26/30 (87.7%). CONCLUSION: Using the CKD-EPI equation leads to
      lower prevalence estimates for CKD than the MDRD equation in a hypertensive
      population treated in general practice.

PMID- 22149719
TI  - Mapping body fat distribution: a key step towards the identification of the
      vulnerable patient?
AB  - Although excess body fat is a significant health hazard, estimation of body fat
      content with the body mass index may not adequately reflect the amount of
      atherogenic adipose tissue (AT), i.e. visceral and ectopic fat. As opposed to
      subcutaneous AT that supposedly acts as a metabolic sink buffering excess dietary
      energy, visceral or intra-abdominal AT depots respond to several external stimuli
      that trigger lipolysis and secretion of free fatty acids (FFAs). Reaching the
      liver, FFAs accumulate in the liver and, over time, promote a chronic condition
      known as non-alcoholic fatty liver disease (NAFLD). The liver of the typical
      NAFLD patient secretes large amounts of very-low-density lipoproteins, the lipid
      content of which may accumulate in additional organs (skeletal muscle, heart, and
      pancreas). Here, we review the evidence emerging from functional and population
      studies that point towards an important role of ectopic fat accumulation in the
      pathophysiology of type 2 diabetes and cardiovascular disease. We conclude that
      although patients with impaired glycemic control or type 2 diabetes are at
      increased cardiovascular disease (CVD) risk, estimating cardiovascular risk goes
      wellbeyond the assessment of glycemic control and traditional CVD risk factors,
      and the estimation of visceral/ectopic fat deposition via readily available
      imaging techniquesshould be considered.

PMID- 22149720
TI  - Topiramate induced bilateral angle-closure glaucoma: low dosage in a short time.
AB  - PURPOSE: The aim of this article is to create awareness among medical colleagues
      regarding the severe ophthalmic side effects associated with topiramate use.
      METHODS: A case of severe acute bilateral angle closure glaucoma with visual
      blurring after oral topiramate therapy. RESULTS: This case was successfully
      managed by discontinuing topiramate and by starting anti-glaucoma medication.
      Intraocular pressure, acute transient myopia, and anterior chamber depth were
      normalized. CONCLUSIONS: It is important for clinicians to recognize these
      conditions and educate patients about these serious adverse effects when
      prescribing topiramate.

PMID- 22149721
TI  - Access to polyfunctionalized diquinanes, hydrindanes, and decalines via TiCl4
      promoted Michael-aldol and Baylis-Hillman reactions.
AB  - The addition of 0.5 equiv of TiCl(4) to (cyclo)alkanones tethered to alpha,beta
      unsaturated ketones afforded polyfunctionalized diquinanes, hydrindanes, and
      decalines. These products, resulting from a Michael-aldol or a Baylis-Hillman
      reaction, can be obtained with high or total diastereoselectivity in moderate to
      high yields. These scaffolds represent interesting building blocks for the
      synthesis of complex natural products.

PMID- 22149722
TI  - beta-D-xylosides stimulate GAG synthesis in chondrocyte cultures due to elevation
      of the extracellular GAG domains, accompanied by the depletion of the intra
      pericellular GAG pools, with alterations in the GAG profiles.
AB  - The familial disease of hereditary multiple exostoses is characterized by
      abnormal skeletal deformities requiring extensive surgical procedures. In
      hereditary multiple exostoses patients there is a shortage in the pericellular
      glycosaminoglycan (GAG) of heparan sulfate (HS), related to defective activity of
      HS glycosyltransferases, mainly in the pericellular regions of chondrocytes. This
      study searched for a novel approach employing xylosides with different aglycone
      groups priming a variety of GAG chains, in attempting to alter the GAG
      compositional profile. Cell cultures of patients with osteochondroma responded to
      p-nitrophenyl beta-D-xyloside by a significant increase in total GAG synthesis,
      expressed mainly in the extracellular domains, limited to chondroitin sulfate).
      The different beta-D-xylosides, in addition to increasing the synthesis of
      extracellular GAGs, led to a significant depletion of the intracellular GAG
      domains. In mouse chondrocyte cultures, beta-D-xylosides with different aglycones
      created a unique distribution of the GAG pools. Of special interest was the
      finding that the naphthalene methanol beta-D-xyloside showed the highest absolute
      levels of HS-GAGs in both extracellular and intra-pericellular moieties compared
      with other beta-D-xylosides and with controls without xyloside. In summary, beta
      D-xylosides can be utilized in chondrocyte cultures to modify the distribution of
      GAGs between the extracellular and intracellular compartments. In addition,
      xylosides may alter the profile of specific GAG chains in each moiety.

PMID- 22149723
TI  - Alterations in the expression of translation factors as molecular markers in
      cadmium-exposed workers.
AB  - Eukaryotic translation initiation factor 3 (eIF3) and elongation factor 1delta
      (eEF-1delta) are novel cadmium (Cd) responsive proto-oncogenes. This research
      investigated the expression of these genes in Cd-exposed workers (n = 58), and to
      evaluate their usefulness as biomarkers of Cd exposure. According to urinary Cd
      concentration, the subjects were divided into four groups (urinary Cd
      concentration >=0.1 MUg/g.Cr, >=1.0 MUg/g.Cr, >=5.0 MUg/g.Cr and >=50.0
      MUg/g.Cr). Subjects exhibited increased severe health problems with higher
      urinary Cd concentrations. The eIF3 and eEF-1delta expression in the blood were
      investigated with real-time PCR. PCR data showed a strong positive correlation
      between blood eEF-1delta and urinary Cd concentrations (r = 0.788, p < 0.01), and
      a weak positive correlation between blood eIF3 expression and urinary Cd
      concentrations (r = 0.569, p < 0.05). These findings, for the first time,
      demonstrate that the blood eEF-1delta overexpression can be used as a molecular
      biomarker of Cd-exposed population.

PMID- 22149724
TI  - Overexpression of SIRT6 in porcine fetal fibroblasts attenuates cytotoxicity and
      premature senescence caused by D-galactose and tert-butylhydroperoxide.
AB  - SIRT6, a member of the yeast silent information regulator 2 (SIR2) family,
      possesses both robust ADP-ribosyltransferase activity and protein deacetylase
      activity depending on NAD(+). It has been shown to maintain genomic stability and
      telomere integrity, and to prevent age-related disorders and premature ageing.
      However, the mechanism by which SIRT6 overexpression affects cellular ageing is
      not well understood. In this study, we investigated the effect of SIRT6
      overexpression on cytotoxicity and ageing syndromes. A full-length cDNA of
      porcine SIRT6 was inserted into pcDNA3.1(-) and subsequently transfected into
      porcine fetal fibroblasts (PFFs). Overexpression of SIRT6 was identified by
      quantitative real-time polymerase chain reaction and western blot assay. The
      cells were incubated with D-galactose and tert-butylhydroperoxide at their
      cytotoxic concentrations. The damage caused by the stresses was detected with
      fluorescence microscopy using 4',6-diamidino-2-phenylindole (DAPI) staining, DNA
      ladder analysis, and observation under transmission electron microscopy. The
      results showed that SIRT6 overexpression in cells decreased damage to the nuclei.
      It also protected against the generation of DNA fragmentation and damage in the
      ultramicrostructure of the cells, especially damage to mitochondria. Our
      observations suggested that one function of SIRT6 in PFFs was to dampen
      cytotoxicity, and, therefore, to decrease the damage that causes premature
      senescence.

PMID- 22149725
TI  - Mesostructured silica containing conjugated polymers formed within the channels
      of anodic alumina membranes from tetrahydrofuran-based solution.
AB  - The synthesis of mesostructured silica from a tetrahydrofuran (THF)-based sol gel
      was carried out in the channels of an anodic alumina membrane (AAM) using the
      evaporation-induced self-assembly (EISA) method. Two different nonionic
      surfactants were used as structure-directing agents, the triblock copolymer
      Pluronic P123 and the oligomer surfactant Brij56. The effect of the relative
      humidity and surfactant concentration on the type of mesophase and orientation of
      the in-channel mesostructures was studied using transmission electron microscopy
      (TEM) and grazing incidence small angel X-ray scattering (GISAXS). The in-channel
      structures obtained in this study were primarily of the 2D hexagonal phase with a
      circular orientation in which the hexagonally packed cylinders form a spiral-like
      shape from the channel wall inward. In addition, a columnar orientation of the
      hexagonal phase, in which the axes of the hexagonally packed cylinders are
      oriented parallel to the channel axes, was also observed. Finally, the use of the
      THF-based synthesis allowed the in situ incorporation of the highly hydrophobic
      yellow-emitting conjugated polymer poly[9,9-dioctylfluorene-co-benzothiadiazole]
      into the in-channel mesostructure upon its formation. The conjugated polymer was
      well distributed within the mesostructure and maintained its optical properties.

PMID- 22149726
TI  - Jewel of the seabed: sea cucumbers as nutritional and drug candidates.
AB  - Marine sources have been attracting the attention of scientists and manufacturers
      worldwide hoping to find new alternatives for biological active substances.
      Promising new research indicates that sea cucumber, which is slug-like in
      appearance and has been a staple in Japan, China and other parts of East Asia
      since ancient times, is beginning to gain popularity as a dietary supplement in
      western countries. The roles of sea cucumber extracts in various physiological
      functions have spurred researchers to investigate the ability of sea cucumber to
      be an alternative in neutraceutical and medical applications. This article
      provides a brief introduction to sea cucumber and reviews its numerous bioactive
      compounds, such as triterpene glycosides, glycosaminoglycans, gangliosides,
      collagen, branched-chain fatty acid and lectins, which serve as potential sources
      of neutraceutical, pharmaceutical and cosmetic agents, thus providing a new
      platform in biochemical research.

PMID- 22149727
TI  - A comparative histological and immunohistochemical study of wound healing
      following incision with a scalpel, CO2 laser or Er,Cr:YSGG laser in the guinea
      pig oral mucosa.
AB  - PURPOSE: This study was undertaken to compare wound healing following incisions
      with either a scalpel, CO(2) laser or Er,Cr:YSGG laser in Guinea pig oral mucosa.
      MATERIALS AND METHODS: Three types of wounds were randomly introduced with either
      a stainless steel scalpel, CO(2) laser or Er,Cr:YSGG laser in the buccal mucosa
      of each of 22 Guinea pigs. Four Guinea pigs were sacrificed on day 1, day 3 and
      day 5 post-surgery. Five Guinea pigs were sacrificed on day 7 and day 14 post
      surgery. Biopsy samples from each oral mucosa wound were examined and the
      expression of TNF-alpha and TGF-beta1 was determined by immunohistochemical
      staining. RESULTS: At day 3 post-surgery, the histological pattern of the healing
      process was similar in the scalpel and Er,Cr:YSGG laser wounds and there were
      more ulcerations present in the CO(2) laser wounds than in the scalpel and
      Er,Cr:YSGG laser wounds. The level of TNF-alpha expression was twice in the laser
      wounds that in the scalpel wounds. A higher level of TGF-beta1 expression was
      seen at day 7 post-surgery and a lower level at day 14 post-surgery in the CO(2)
      laser wounds than in the scalpel and Er,Cr:YSGG laser wounds. CONCLUSIONS: The
      Er,Cr:YSGG laser has many advantages for oral surgery due to a low inflammatory
      response and minimal damage of the tissue. Although a CO(2) laser has better
      hemostatic ability, its use causes greater tissue damage than a scalpel and
      Er,Cr:YSGG laser. However, further larger studies would be needed before fully
      endorsing its widespread use.

PMID- 22149733
TI  - Polymersomes in "gelly" polymersomes: toward structural cell mimicry.
AB  - We demonstrate here the formation of compartmentalized polymersomes with an
      internal "gelly" cavity using an original and versatile process. Nanosize
      polymersomes of poly(trimethylene carbonate)-b-poly(L-glutamic acid) (PTMC-b
      PGA), formed by a solvent displacement method are encapsulated with a rough
      "cytoplasm mimic" in giant polymersomes of poly(butadiene)-b-poly(ethylene oxide)
      PB-b-PEO by emulsion-centrifugation. Such a system constitutes a first step
      toward the challenge of structural cell mimicry with both "organelles" and
      "cytoplasm mimics". The structure is demonstrated with fluorescence labeling and
      confocal microscopy imaging with movies featuring the motion of the inner
      nanosize polymersomes in larger vesicles. Without "cytoplasm mimic", the motion
      was confirmed to be Brownian by particle tracking analysis. The inner nanosize
      polymersomes motion was blocked in the presence of alginate, but only hindered in
      the presence of dextran. With the use of such high molecular weight and
      concentrated polysaccharides, the crowded internal volume of cells, responsible
      for the so-called "macromolecular crowding" effect influencing every
      intracellular macromolecular association, seems to be efficiently mimicked. This
      study constitutes major progress in the field of structural biomimicry and will
      certainly enable the rise of new, highly interesting properties in the field of
      high-added value soft matter.

PMID- 22149734
TI  - Expanding eligibility, cutting costs--a Medicaid update.

PMID- 22149735
TI  - Smoking and the First Amendment.

PMID- 22149736
TI  - Generic atorvastatin and health care costs.

PMID- 22149737
TI  - The constitutionality of the ACA's Medicaid-expansion mandate.

PMID- 22149738
TI  - Low angle light scattering analysis: a novel quantitative method for functional
      characterization of human and murine platelet receptors.
AB  - BACKGROUND: Determinations of platelet receptor functions are indispensable
      diagnostic indicators of cardiovascular and hemostatic diseases including
      hereditary and acquired receptor defects and receptor responses to drugs.
      However, presently available techniques for assessing platelet function have some
      disadvantages, such as low sensitivity and the requirement of large sample sizes
      and unphysiologically high agonist concentrations. Our goal was to develop and
      initially characterize a new technique designed to quantitatively analyze
      platelet receptor activation and platelet function on the basis of measuring
      changes in low angle light scattering. METHODS: We developed a novel technique
      based on low angle light scattering registering changes in light scattering at a
      range of different angles in platelet suspensions during activation. RESULTS: The
      method proved to be highly sensitive for simultaneous real time detection of
      changes in size and shape of platelets during activation. Unlike commonly-used
      methods, the light scattering method could detect platelet shape change and
      aggregation in response to nanomolar concentrations of extracellular nucleotides.
      Furthermore, our results demonstrate that the advantages of the light scattering
      method make it a choice method for platelet receptor monitoring and for
      investigation of both murine and human platelets in disease models. CONCLUSIONS:
      Our data demonstrate the suitability and superiority of this new low angle light
      scattering method for comprehensive analyses of platelet receptors and functions.
      This highly sensitive, quantitative, and online detection of essential
      physiological, pathophysiological and pharmacological-response properties of
      human and mouse platelets is a significant improvement over conventional
      techniques.

PMID- 22149739
TI  - Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary
      cancers.
AB  - BACKGROUND: Tumor mesothelin overexpression is present in different malignancies,
      including the majority of patients with pancreatic or biliary cancers. The
      objective of this study was to evaluate the use of shed serum mesothelin and
      megakaryocyte potentiating factor (MPF) concentrations as biomarkers for these
      cancers. METHODS: A total of 151 individuals, divided into five groups, were
      retrospectively analyzed: healthy donors (n=15), patients with benign non
      pancreatic conditions (n=52), benign pancreatic conditions (n=33), biliary
      carcinoma (n=9), and pancreatic ductal adenocarcinoma (n=42). Mesothelin and MPF
      concentrations were measured in serum with the MesomarkTM and Human MPF ELISA,
      respectively. RESULTS: Mesothelin and MPF concentrations did not significantly
      differ among the five individual participant groups (p=0.34, p=0.33,
      respectively), nor did any other combination and pair-wise comparison of the
      participant groups demonstrated a significant difference in biomarker
      concentrations. In patients with pancreatic cancer, mesothelin or MPF
      concentrations were not associated with tumor stage (p=0.87, p=0.48,
      respectively) or differentiation grade (p=0.73, p=0.52, respectively).
      CONCLUSIONS: Serum mesothelin and MPF concentrations, measured with standard
      available ELISAs, were not specific for benign or pancreatic disease. Both
      biomarkers were not elevated in patients with pancreatic or biliary cancers, and
      consequently do not appear to be useful biomarkers for these malignancies.

PMID- 22149741
TI  - Comparison of different collection procedures and two methods for DNA isolation
      from saliva.
AB  - BACKGROUND: The non-invasive, flexible and easy sample collection makes saliva an
      interesting source of DNA for research and diagnostic purposes. The aim of our
      study was to find the most suitable collection method for biological material
      from the oral cavity and the most effective DNA isolation technique for further
      analytic applications. METHODS: DNA was isolated from swabs, Salivette saliva,
      whole saliva and samples collected with a commercial set for scraping of buccal
      cells. Phenol-chloroform extraction and isolation using a silica membrane based
      commercial kit were compared. Quantity of bacterial and human genomic DNA was
      estimated using real time PCR. The effects of storage conditions on DNA recovery
      were assessed. RESULTS: Sample collection techniques significantly affected the
      quantity of DNA for both, silica membrane based and phenol-chloroform isolations.
      Whole saliva provided the largest number of bacterial and human genome copies
      after both extraction methods. Storage for 36 months at -20 degrees C reduced
      recovery of human genomic DNA five times after silica membrane based extraction
      and 10 times after phenol-chloroform isolation. CONCLUSIONS: Whole saliva was
      found to be the most suitable material for human and bacterial DNA isolation.
      Both compared methods are useful considering the quantity of extracted DNA.

PMID- 22149740
TI  - Faecal haemoglobin concentrations by gender and age: implications for population
      based screening for colorectal cancer.
AB  - BACKGROUND: Faecal immunochemical tests (FIT) are becoming widely used in
      colorectal cancer screening. Estimation of faecal haemoglobin concentration in a
      large group prompted an observational study on gender and age. METHODS: A single
      estimate of faecal haemoglobin concentration was made using quantitative
      automated immunoturbidimetry. Potential reference intervals were calculated for
      men and women and for age quintiles according to the Clinical and Laboratory
      Standards Institute Approved Guideline. The percentages of positive results were
      calculated at a number of concentrations. The percentages of individuals who fell
      into different risk groups were assessed. RESULTS: The 97.5 percentiles,
      potential upper reference limits, were 519 ng haemoglobin/mL (90% CI: 468-575)
      for men and 283 ng haemoglobin/mL (90% CI: 257-316) for women. Concentrations
      increased with age in both genders. Decision limits have advantages over
      reference intervals. At any cut-off concentration, more men are declared positive
      than women and more older people are declared positive than younger people.
      Future risk of neoplasia is higher in men than in women and in older people.
      CONCLUSIONS: Faecal haemoglobin concentrations vary with gender and age. More
      tailored strategies are needed in screening programmes. Faecal haemoglobin
      concentration could be included in individual risk assessment scores. These data
      should assist in screening programme design.

PMID- 22149742
TI  - The hCG assay or pregnancy test.
AB  - This review examines human chorionic gonadotropin (hCG) or pregnancy tests from
      multiple perspectives. It first investigates the molecule hCG and shows that the
      term represents five independent molecules differing in carbohydrate and meric
      structure that share a common amino acid sequence. The review goes on to show
      that multiple degradation produces also the need to be tested for an hCG or
      pregnancy test to be optimally efficient. The review then carefully examines the
      literature showing the sensitivity and specificity of automated laboratory tests.
      Point-of-care pregnancy tests are then investigated along with over-the-counter
      pregnancy tests. Appropriate detection of hyperglycosylated hCG, nicked hCG,
      nicked hCG missing the beta-subunit C-terminal peptide and nicked
      hyperglycosylated hCG is a limitation on all pregnancy tests. In the opinion of
      the author, just one automated laboratory test, the Siemen's Immulite, one point
      of-care test, the Beckman-Coulter Icon 25, and one brand of over-the-counter
      device, First Response, are suitable for early pregnancy detection and possibly
      other applications.

PMID- 22149743
TI  - Anti-thyroid peroxidase antibodies are associated with the absence of distant
      metastases in patients with newly diagnosed breast cancer.
AB  - BACKGROUND: The presence of thyroid peroxidase antibodies (TPOab) are reported to
      be associated with improved outcome among breast cancer patients. We evaluated
      the correlation between TPOab and diagnostic parameters among newly diagnosed
      breast cancer patients. METHODS: Three hundred and fourteen newly diagnosed
      patients with breast cancer, diagnosed and treated in Bethesda Essen between
      January 2002 and June 2006, were included in this study; 258 (82.2%) without
      TPOab (<=100 IU/mL) and 56 (17.8%) with TPOab (>100 IU/mL). Blood analysis was
      performed to measure serum levels of carcinoembryonic antigen (CEA), cancer
      antigen 15-3 (CA-15-3), free triiodothyronine (fT3), free thyroxine (fT4),
      thyroid-stimulating hormone (TSH) and TPOab by radioimmunoassay. Data regarding
      age, tumor size, grading, TNM classification, receptor status, lymph node, and
      distant metastases were collected and analyzed from patient reports. Statistics
      were performed using Pearson's chi2-test and logistic regression analysis.
      RESULTS: There were no incidences of distant metastasis among 56 patients with
      TPOab, whereas 17 (6.6%) of 258 cases without TPOab displayed distant metastases
      (p=0.04). Logistic regression showed an inverse association of TPOab with CA-15-3
      and CEA levels (p<0.001, respectively). Both groups, with and without TPOab,
      revealed no significant differences with respect to age, tumor size, grading, TNM
      classification, fT3, fT4, and receptor status. TPOab positive patients had higher
      TSH levels (2.55+/-3.58), compared to TPOab negative cases (1.20+/-1.15)
      (p<0.001). CONCLUSIONS: TPOab occurrence is associated with significantly lower
      frequency of distant metastases in breast cancer. TPOab level inversely
      correlates with the conventional tumor markers CA-15-3 and CEA.

PMID- 22149744
TI  - Monitoring quality indicators in laboratory medicine does not automatically
      result in quality improvement.
AB  - BACKGROUND: Data on quality indicators (QIs) should be collected over time in
      order to identify and continuously monitor clinical laboratory performance and to
      improve patient safety by identifying and implementing effective interventions.
      The aim of the present study was to ascertain whether the utilization of a set of
      quality indicators over a 3-year period resulted in an improvement in the
      efficiency and effectiveness of an individual laboratory. METHODS: Over a 3-year
      time interval (2009-2011), a series of 38 QIs covering all stages of the total
      testing process (21 in the pre-analytic, nine in the analytic and eight in the
      post-analytic phase) was monitored. RESULTS: On the basis of their patterns, QIs
      have been grouped into the following categories: [1] seven QIs of the pre
      analytical phase and three of the intra-analytical phase with a significant trend
      and a significant linearity demonstrating an improvement over time; [2] 10 QIs of
      the pre-analytical and two of the intra-analytical phase with a significant trend
      and a non-significant linearity demonstrating that changes were not constant; [3]
      two QIs of the pre-analytical and one of the intra-analytical phase with a non
      significant trend and significant linearity showing neither improvement nor
      worsening; and [4] two QIs of the pre-analytical and three of the intra
      analytical phase with a non-significant trend and non-significant linearity.
      CONCLUSIONS: Data on a set of QIs collected over a 3-year time-frame demonstrate
      that processes and indicators under the control of the clinical laboratory had
      improved much more than processes requiring close co-operation between the
      laboratory and care teams.

PMID- 22149745
TI  - Serum concentration of neopterin on admission does not improve the diagnostic
      performance of highly-sensitive troponin I.

PMID- 22149746
TI  - Soluble transcobalamin receptor, sCD320, is present in human serum and relates to
      serum cobalamin - establishment and validation of an ELISA.
AB  - BACKGROUND: The cell-surface receptor, TCblR/CD320, binds and internalizes
      transcobalamin-bound cobalamin. So far, no assay has been developed in order to
      quantify the soluble form of the receptor. METHODS: This study developed an ELISA
      employing a monoclonal antibody that recognized the extracellular domain of CD320
      as capture antibody and a biotinylated polyclonal antibody for detection. Serum
      samples were analyzed from blood donors (n==153) and samples from patients
      referred for analysis of serum cobalamin [n=757, serum cobalamin 75-2000 pg/mL
      (55-1476 pmol/L)]. RESULTS: The ELISA specifically measured soluble CD320 with a
      quantification limit of 1.6 arbitrary units and a total variation of 4%-8%. Size
      exclusion chromatography was used which showed that the immunoreactive protein
      observed in serum eluted in the same position as soluble CD320 in the calibrator.
      Male donors (n=76) showed significantly higher median concentration [18 arbitrary
      units (arb.u.)] than female donors (n=77, median 16 arb.u.), but the absolute
      difference was marginal and suggested that a common reference interval of 12-97
      arb.u. can be used. A positive correlation was observed between levels of soluble
      CD320 and serum cobalamin with median levels increasing from 17 arb.u. [n=203,
      cobalamin 75-270 pg/mL (55-200 pmol/L)] to 23 arb.u. [n=350, cobalamin 814-2000
      pg/mL (601-1476 pmol/L)], p<0.0001. CONCLUSIONS: An ELISA was established for
      measurement of soluble CD320 and it was shown that the protein is present in
      human serum. The serum concentrations of soluble CD320 correlated positively with
      serum cobalamin levels.

PMID- 22149747
TI  - Ultrasound markers for the detection of women at risk  of developing pre
      eclampsia.
AB  - Pre-eclampsia (PE) is a consequence of an abnormal placental invasion. Uterine
      artery Doppler (Ut-AD) is directly related to trophoblastic invasion of the
      spiral arteries, which occurs before 18 weeks' gestation. A correct
      interpretation of Ut-AD indices and waveform patterns requires a rigorous and
      standardized methodology, in particular for the definition of notches. To date,
      aspirin is the only treatment associated with a decreased incidence of PE, and
      early identification of women at risk is crucial to optimize its use. The
      diagnostic performance of Ut-AD as a screening test should take into account the
      characteristics of the population studied. In women at high-risk of PE (i.e.,
      women with a previous history of PE), results vary from a detection rate of 63%,
      with 25% false-positive results for all forms of PE, to 91% detection with 5%
      false-positive for early PE if repeated measurements, combined with maternal
      characteristics, are performed. Multicenter randomized clinical trials failed to
      demonstrate a benefit from administering aspirin in low-risk women with abnormal
      Ut-AD. In unselected populations, the use of Ut-AD, alone or integrated into
      algorithms including maternal characteristics, cannot be recommended for clinical
      practice at any gestational age. Combination with biological markers is a new
      field of research that could improve the performance of Ut-AD.

PMID- 22149749
TI  - A comparative analysis of the Iris iQ200 with manual microscopy as a diagnostic
      tool for dysmorphic erythrocytes in urine.

PMID- 22149750
TI  - A microbial oasis in the hypersaline Atacama subsurface discovered by a life
      detector chip: implications for the search for life on Mars.
AB  - The Atacama Desert has long been considered a good Mars analogue for testing
      instrumentation for planetary exploration, but very few data (if any) have been
      reported about the geomicrobiology of its salt-rich subsurface. We performed a
      Mars analogue drilling campaign next to the Salar Grande (Atacama, Chile) in July
      2009, and several cores and powder samples from up to 5 m deep were analyzed in
      situ with LDChip300 (a Life Detector Chip containing 300 antibodies). Here, we
      show the discovery of a hypersaline subsurface microbial habitat associated with
      halite-, nitrate-, and perchlorate-containing salts at 2 m deep. LDChip300
      detected bacteria, archaea, and other biological material (DNA,
      exopolysaccharides, some peptides) from the analysis of less than 0.5 g of ground
      core sample. The results were supported by oligonucleotide microarray
      hybridization in the field and finally confirmed by molecular phylogenetic
      analysis and direct visualization of microbial cells bound to halite crystals in
      the laboratory. Geochemical analyses revealed a habitat with abundant hygroscopic
      salts like halite (up to 260 g kg(-1)) and perchlorate (41.13 MUg g(-1) maximum),
      which allow deliquescence events at low relative humidity. Thin liquid water
      films would permit microbes to proliferate by using detected organic acids like
      acetate (19.14 MUg g(-1)) or formate (76.06 MUg g(-1)) as electron donors, and
      sulfate (15875 MUg g(-1)), nitrate (13490 MUg g(-1)), or perchlorate as
      acceptors. Our results correlate with the discovery of similar hygroscopic salts
      and possible deliquescence processes on Mars, and open new search strategies for
      subsurface martian biota. The performance demonstrated by our LDChip300 validates
      this technology for planetary exploration, particularly for the search for life
      on Mars.

PMID- 22149759
TI  - Leisure activities, caregiving demands and catecholamine levels in dementia
      caregivers.
AB  - This study examined whether satisfaction from leisure activities moderates the
      relationship between caregiving demands (i.e., hours per day spent caring for a
      spouse with dementia) and resting levels of the catecholamines norepinephrine
      (NE) and epinephrine (EPI). Spousal caregivers (n = 107; mean age = 73.95 +/-
      8.12 years) were assessed in home for plasma levels of NE and EPI, amount of care
      provided, and leisure satisfaction. Regression was used to determine whether
      leisure satisfaction moderated the relationship between hours providing care per
      day and catecholamine levels. A significant interaction was found between hours
      caregiving and leisure satisfaction for NE, but not for EPI. Post hoc regressions
      were conducted for both NE and EPI. At low leisure satisfaction, time spent
      caring for a spouse was positively associated with plasma NE (beta = 0.41; p =
      0.005) and EPI (beta = 0.44; p = 0.003). In contrast, at high levels of
      satisfaction, time caregiving was not significantly associated with plasma NE
      (beta = -0.08; p = 0.57) or EPI (beta = 0.23; p = 0.12). These findings suggest
      that leisure satisfaction may protect caregivers from increases in
      catecholamines, which have been implicated in cardiovascular risk. Further
      support for these findings may impact psychological treatments for distressed
      caregivers.

PMID- 22149758
TI  - Monetary-based consequences for drug abstinence: methods of implementation and
      some considerations about the allocation of finances in substance abusers.
AB  - Conceptualizing drug abuse within the framework of behavioral theories of choice
      highlights the relevance of environmental variables in shifting behavior away
      from drug-related purchases. Choosing to use drugs results in immediate and
      certain consequences (e.g., drug high and relief from withdrawal), whereas
      choosing abstinence typically results in delayed, and often uncertain,
      consequences (e.g., improved health, interpersonal relationships, money).
      METHODS: This is a selective review of the literature on Contingency management
      (CM). RESULTS: We highlight a variety of methods to deliver CM in practical,
      effective, and sustainable ways. We consider a number of parameters that are
      critical to the success of monetary-based CM, and the role of the context in
      influencing CM's effects. To illustrate the broad range of applications of CM, we
      also review different methods for arranging contingencies to promote abstinence
      and other relevant behavior. Finally, we discuss some considerations about how
      drug-dependent individuals allocate their finances in the context of CM
      interventions. CONCLUSIONS: Contingency management (CM) increases choice for drug
      abstinence via the availability of immediate, financial-based gains, contingent
      on objective evidence of abstinence.

PMID- 22149760
TI  - Contraceptives with novel benefits.
AB  - INTRODUCTION: Progesterone receptor (PR) agonists (progestins) and antagonists
      are developed for female contraceptives. However, non-contraceptive applications
      of newer progestins and PR modulators are being given more attention. AREAS
      COVERED: The newer PR agonists including drospirenone, nomegestrol, trimegestone,
      dienogest and nestorone are being evaluated as contraceptives with health
      benefits because of their unique pharmacological properties. The selective PR
      modulators (SPRM; PR antagonists with PR agonistic properties) are under
      development not only for emergency contraception but also for other health
      benefits such as the treatment of endometritis and leiomyoma. After searching the
      literature from PubMed, clinicaltrials.gov and patent database, this review
      focuses on the effects and mechanisms of these progestins, and SPRMs as
      contraceptives with other health benefits. EXPERT OPINION: PR agonists and
      antagonists that have novel properties may generate better contraceptive effects
      with other health benefits.

PMID- 22149761
TI  - Tachykinin NK2 receptor antagonists. A patent review (2006 - 2010).
AB  - INTRODUCTION: Tachykinins are endogenous peptide neurotransmitters, acting
      through the NK1, NK2 and NK3 receptors, at central and peripheral level. At
      peripheral level, they are involved in contraction of smooth muscle, secretion of
      water and ion from epithelia, as well as modulation of visceral pain sensitivity.
      Tachykinin NK2 receptor antagonists have the potential to be useful in the
      treatment of various gastrointestinal, genitourinary and CNS diseases. AREAS
      COVERED: In this review, an overview of the patenting activity in the last 5
      years is provided. Patents from different companies and research groups are
      discussed for their novelty and evaluated in relation to proposed indications and
      clinical studies. Relevant biological data are also presented. Patents claiming
      new therapeutic indications are included in a dedicated section. EXPERT OPINION:
      Although there is still no tachykinin NK2 receptor antagonist approved for use in
      human therapy, research in the field is still proposing new compounds and
      possible uses. A number of candidates are being evaluated in Phase II clinical
      studies, in indications ranging from gastrointestinal disorders to inflammatory
      diseases. The results of these studies will indicate the role of tachykinin NK2
      receptor antagonists in human therapy.

PMID- 22149762
TI  - Trisomy greatly enhances interstitial crossing over in a translocation
      heterozygote of Secale.
AB  - Chromosomal rearrangements, including reciprocal translocations, may prevent
      recombinational transfer of genes from a donor genotype to a recipient,
      especially when the gene is located in an interstitial segment. The effect of
      trisomy of chromosome arm 1RS on recombination was studied in translocation
      heterozygote T248W of rye ( Secale cereale ), involving chromosome arms 1RS and
      6RS. (Pro)metaphase I configuration frequencies were analyzed. Crossing over,
      estimated as chiasma parameters, in five genetically different euploid
      heterozygotes was compared with those of 10 different single arm trisomics. The
      addition of 1RS greatly altered the crossing over pattern around the
      translocation break point, with a special increase in the interstitial segment of
      6RS and adjoining regions, normally hardly accessible to recombination.
      Furthermore, there was considerable variation between plants of closely related
      genotypes. Heterogeneity widens the distribution of crossing overs, including
      segments normally not accessible to recombination, but decreases average
      recombination in other segments. The extra chromosome and abnormal segregants are
      eliminated by using the trisomic as the pollen parent.

PMID- 22149763
TI  - A comparative study of root defect coverage using an acellular dermal matrix with
      and without a recombinant human platelet-derived growth factor.
AB  - BACKGROUND: The objective of this case series is to compare root defect coverage
      results and healing responses of bilateral recession defects treated with
      acellular dermal matrix (ADM) with and without recombinant human platelet-derived
      growth factor (rhPDGF). METHODS: Seventeen patients with 40 bilateral gingival
      recession defects were compared. Each defect was >=2 mm and treated with ADM and
      a coronally advanced flap. Using split-mouth design, the control-side ADM was
      hydrated in sterile saline, whereas the test-side ADM was hydrated in rhPDGF. The
      patients were evaluated at 1 week, 1 month, 3 months, and 6 months. Standardized
      measurements were taken preoperatively at 3 and 6 months. Healing was clinically
      assessed at 1 week and 1 month post-surgically. RESULTS: Both test and control
      groups showed significant gain in root defect coverage over the 6-month period
      for all individuals, with the test group showing a 69.0% gain and the control
      group showing a 76.7% gain. Patients divided into Miller Class I and Class III
      defects were also found to have a significant gain in root defect coverage over 6
      months. The test group showed 84.1% gain, and the control group showed 84.7% gain
      for Miller Class I defects. For Miller Class III defects, the test group showed
      51.5% gain, and the control group showed a 60.8% gain. One week after surgery,
      35% of the test group showed better healing, whereas 15% of the control group
      showed better healing. One month after surgery, 20% of the test group showed
      better healing, whereas 15% of the control group showed better healing.
      CONCLUSION: Based on the results of this case series, there were no statistically
      or clinically significant differences in root defect coverage, keratinized
      tissue, clinical attachment level, or clinical healing for treatment of root
      recession with a coronally advanced flap and ADM with and without rhPDGF.

PMID- 22149764
TI  - Sexual risk behaviors and acceptability of HIV pre-exposure prophylaxis among HIV
      negative gay and bisexual men in serodiscordant relationships: a mixed methods
      study.
AB  - The objective of this mixed methods study was to examine current sexual risk
      behaviors, acceptability and potential adoption of pre-exposure prophylaxis
      (PrEP) for HIV prevention, and sexual behavior intentions with PrEP adoption
      among HIV-negative gay and bisexual men (GBM) in HIV serodiscordant
      relationships. A multiracial/ethnic sample of 25 HIV-negative GBM in
      serodiscordant relationships completed a qualitative interview and a brief
      interviewer-administered survey. A modified grounded theory approach was used to
      identify key themes relating to acceptability and future adoption of PrEP.
      Participants reported engaging in sexual risk behaviors that place them at risk
      for HIV infection. Participants also reported a high level of acceptability for
      PrEP and willingness to adopt PrEP for HIV prevention. Qualitative themes
      explaining future PrEP adoption included: (1) the opportunity to engage in sex
      using a noncondom HIV prevention method, (2) protection from HIV infection, and
      (3) less anxiety when engaging in sex with an HIV-positive partner. Associated
      with the future adoption of PrEP, a majority (64%) of participants indicated the
      likelihood for an increase in sexual risk behaviors and a majority (60%) of
      participants also indicated the likelihood for a decrease or abandonment of
      condom use, both of which are in contrast to the findings from the large iPrEx
      study. These findings suggest that the use of PrEP by HIV-negative GBM in
      serodiscordant relationships carries with it the potential for risk compensation.
      The findings suggest that PrEP only be offered as part of a comprehensive HIV
      prevention strategy that includes ongoing risk reduction counseling in the
      delivery of PrEP to help moderate risk compensation.

PMID- 22149765
TI  - Causes of hospitalization and perceived access to care among persons newly
      diagnosed with HIV infection: implications for HIV testing programs.
AB  - There has been little research on the causes of hospitalization when patients are
      first diagnosed with HIV in the hospital. Reduced access to care could partially
      explain inpatient diagnosis. We sought to determine if the patients diagnosed as
      inpatients are hospitalized due to a HIV-related cause versus some other causes,
      to compare access to care of patients diagnosed with HIV in hospital and
      outpatient settings, and to determine factors associated with access to care.
      Participants were newly diagnosed with HIV and recruited between January 2006 and
      August 2007. The reason for hospitalization was classified as HIV-related, other
      infectious cause, noninfectious cause, or miscellaneous cause. Access to care was
      self-reported using a six-item scale and scores were compared with the t test.
      Multivariate linear regression determined factors associated with improved access
      to care. Of 185 participants in the study, 78 were diagnosed in hospital and 107
      in outpatient settings. Thirty-two percent of participants were female, 90% were
      racial/ethnic minority, 45% had no high school diploma, and 85% were uninsured.
      HIV-related conditions accounted for 60% of admissions, followed by non
      infectious causes (20%) and other infectious causes (17%). Inpatients did not
      report less access to care than patients diagnosed while outpatients.
      Multivariate analysis demonstrated improvement in access to care with better
      health insurance (p = 0.01) and greater education (p = 0.08). HIV-related
      preventable conditions account for many hospitalizations when patients are first
      diagnosed with HIV. While socioeconomic factors are associated with perceived
      access to care, persons diagnosed in the inpatient setting do not report lower
      perceived access to care than persons diagnosed as outpatients, suggesting other
      barriers to earlier diagnosis.

PMID- 22149766
TI  - Development of a framework for HIV/AIDS prevention programs in African American
      churches.
AB  - Churches and other faith-based organizations (FBOs) are a vital resource for HIV
      prevention and education efforts in African American communities. Few models
      describe how churches and FBOs have implemented such efforts within their
      congregations or communities, the challenges they faced, or the changes that
      resulted from such efforts. This article presents a framework for implementing
      HIV/AIDS prevention programs in African American churches based upon a
      qualitative investigation of Project FAITH (Fostering AIDS Initiatives that
      Heal), an HIV education and stigma reduction demonstration project conducted in
      South Carolina. Between 2007-2008 in-depth interviews were conducted with 8
      pastors, 4 technical assistance providers, and 2 project champions; 22 care team
      members also participated in focus groups to identify domains associated with
      project implementation. Data analysis was conducted using a grounded theory
      approach and inputs, enablers, inhibitors, mediators, and outputs associated with
      HIV/AIDS prevention programs conducted as part of Project FAITH were identified.
      Furthermore, the framework includes the influences of public policy and stigma on
      the faith-based HIV/AIDS prevention programs in this study. The framework calls
      for the identification of individuals (members of the congregation and church
      leadership) who are passionate about and devoted to addressing HIV/AIDS, and
      provides specific mechanisms (i.e., health ministries) through which these
      individuals can organize, strategies for HIV/AIDS implementation, and areas of
      technical assistance and capacity building to maximize effectiveness of such
      efforts.

PMID- 22149768
TI  - Assessment of antimicrobial, insecticidal and genotoxic effects of Melia
      azedarach L. (chinaberry) naturalized in Anatolia.
AB  - In this study, antibacterial, antifungal, insecticidal and genotoxic activities
      of the fruit and leaf extracts of Melia azedarach of Turkish origin were
      evaluated for the first time. The antimicrobial activity was assessed against
      Gram (+) and (-) bacteria, four Candida species and three dermatophytic fungus
      (Trichophyton rubrum, Epidermophyton floccosum and Microsporum gypseum). The
      insecticidal activity of the methanolic fruit extract was performed against the
      larvae of Aedes aegpyti, Culex pipiens and Culex quinquefasciatus. The
      genotoxicity of this extract was evaluated against Drosophila melanogaster by
      somatic mutation and recombination test. The extracts showed higher antibacterial
      effect against Gram (-) strains (16-32 MUg ml(-1) of minimal inhibition
      concentration, MIC), while the leaf extracts were more effective on Candida
      albicans (32 MUg ml(-1)of MIC). The extracts did not exhibit insecticidal
      activity and genotoxicity. Total phenol and flavonoid contents of the extracts
      were determined spectrophotometrically, and the ethyl acetate extract of the
      leaves was the richest in total flavonoids.

PMID- 22149767
TI  - The impact of stigma on medication adherence among HIV-positive adolescent and
      young adult females and the moderating effects of coping and satisfaction with
      health care.
AB  - To explore whether HIV stigma negatively impacts adherence to antiviral
      medications in HIV-infected adolescent women, moderational analysis was conducted
      and factors identified that could alter said relationship. Study participants
      were 178 adolescent females age 15-24, enrolled between 2003-2005, from 5
      different cities and 60 provided adherence information. Findings reported by this
      cohort of 60 adolescent women included: medication adherence, 64.3% reporting
      adherence at baseline and 45.0% at 12 months; HIV stigma score of 57.60 (standard
      deviation [SD], 11.83; range, 25-86). HIV stigma was not found to be a
      significant predictor when binary logit regression was run with medication
      adherence at 1 year. Using moderational analysis, factors that could moderate
      stigma's effect on medication adherence was still pursued and identified the
      following to be significant at 12 months: health care satisfaction (B = -0.020,
      standard error [SE] = 0.010, p < .05); and Coping (proactive coping strategies [B
      = 0.012, SE = 0.005, p < .05]; turning to family [B = 0.012, SE = 0.016, p <
      0.05]; spiritual coping [B = 0.021, SE = 0.010, p < 0.05]; professional help [B =
      0.021, SE = 0.010, p < 0.05]; physical diversions [B = 0.016, SE = 0.007, p <
      0.05]). Factors that had no significant moderating effects included: social
      support measures (mean = 74.9; median = 74.0) and depression score greater than
      16 = 43%. We conclude that HIV-infected adolescent women experience HIV stigma
      and poor adherence over time. Factors like health care satisfaction and coping
      may minimize stigma's effect on medication adherence. Our findings are tempered
      by a small sample size and lack of a direct relationship between stigma and
      adherence on binary logit regression analysis.

PMID- 22149769
TI  - Effect of pitavastatin vs. rosuvastatin on international normalized ratio in
      healthy volunteers on steady-state warfarin.
AB  - OBJECTIVE: Statins have been shown to impact international normalized ratio (INR)
      when coadministered with warfarin. The aim of this study was to assess the effect
      of pitavastatin compared with rosuvastatin on steady-state pharmacodynamics (PD)
      of warfarin by measuring INR in healthy adult subjects. METHODS: Subjects
      received oral doses of warfarin 5 mg once daily on days 1 through 3. The dose was
      titrated on days 4 through 9 to reach a steady-state INR of 1.5 to 2.2. Warfarin
      was continued on days 10 through 21 and pitavastatin 4 mg or rosuvastatin 40 mg
      was administered once daily on days 14 through 22. After a 14-day washout period,
      the process was repeated with the alternate statin. STUDY NUMBER: NK-104-4.03US.
      RESULTS: For pitavastatin, mean INR changed from 1.73 +/- 0.18 (n = 42) on day 14
      before starting statin dosing, to 1.78 +/- 0.29 (n = 42) on day 22 at treatment
      end; the difference in INR was not significant (p = 0.219). For rosuvastatin,
      mean INR increased significantly from 1.74 +/- 0.20 (n = 43) at baseline to 1.90
      +/- 0.30 (n = 43) at treatment end (p < 0.001). Rosuvastatin caused a
      significantly greater increase in INR than pitavastatin (p < 0.001). CONCLUSION:
      Steady-state INR during warfarin treatment did not change significantly when
      pitavastatin 4 mg was added to the regimen, while a significant increase was
      observed when rosuvastatin 40 mg was added. The effect of rosuvastatin on INR was
      significantly larger than the effect of pitavastatin. This study is limited
      because it was done in healthy volunteers. Further studies in patient populations
      are needed to better understand the clinical significance of the results.

PMID- 22149770
TI  - Establishing the place in therapy of bilastine in the treatment of allergic
      rhinitis according to ARIA: evidence review.
AB  - BACKGROUND: The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines
      development group examined the properties of oral H(1)-antihistamines and made
      proposals about an 'optimal' drug. Several criteria should be met by oral H(1)
      antihistamines in terms of their pharmacological, and clinical efficacy and
      safety profiles. OBJECTIVE: Bilastine, a new H(1)-antihistamine, has been
      approved in 28 European countries for the symptomatic treatment of allergic
      rhinoconjunctivitis and urticaria in adults and children older than 12 years. To
      determine its potential place in therapy in the treatment of allergic rhinitis,
      this manuscript examines whether bilastine meets the criteria defined in the
      European Academy of Allergy and Clinical Immunology (EAACI)/ARIA proposals for
      oral H(1)-antihistamines. METHODS: The optimal properties of oral H(1)
      antihistamines and current ARIA recommendations for their use in allergic
      rhinitis are presented, as well as relevant pharmacological and clinical data for
      bilastine obtained from the published literature that specifically address the
      defined criteria. RESULTS: Bilastine is a potent inhibitor of the histamine H(1)
      receptor. Data from preclinical studies have confirmed its selectivity for the
      histamine H(1) receptor over other receptors, and demonstrated antihistaminic
      properties in vitro and in vivo. Bilastine does not interfere with the cytochrome
      P450 system and is devoid of cardiac side effects. Studies in healthy volunteers
      and patients have shown that bilastine does not affect driving ability, cardiac
      conduction or alertness. In large pivotal randomized, placebo-controlled trials
      (RCTs), bilastine had a favourable safety profile. Bilastine 20 mg once daily
      improved all nasal and ocular symptoms of allergic rhinitis with greater efficacy
      than placebo and comparable to that of cetirizine and desloratadine. Moreover,
      bilastine was shown to improve quality of life, an important outcome of RCTs in
      allergic diseases. There were no significant changes in laboratory tests,
      electrocardiograms or vital signs. A potential limitation of this assessment of
      bilastine is that it is a literature-based review and the findings are dependent
      upon the quality of the published evidence. CONCLUSIONS: Bilastine meets current
      EAACI/ARIA criteria for medications used in the treatment of allergic rhinitis.

PMID- 22149771
TI  - Corneal haze following disruption of epithelial basement membrane on ultra-high
      resolution OCT following femtosecond LASIK.
AB  - PURPOSE: To analyze in vivo structural properties of a case with interface haze
      that developed after femtosecond laser-assisted LASIK. METHODS: Case report.
      RESULTS: A 42-year-old man underwent uncomplicated LASIK. Four months after the
      surgery he developed regression of his refractive error and interface haze in
      both eyes. Flap thickness was calculated as 73 MUm and 81 MUm in the right and
      left eyes, respectively. A novel ultra-high-resolution spectral domain optical
      coherence tomography (OCT) system was used to demonstrate in vivo morphology of
      the cornea. On ultra-high-resolution OCT, haze was demonstrated as increased
      bright white reflectivity of the flap interface. Areas of focal disruption of the
      basement membrane and Bowman layer corresponded with the most significant areas
      of interface haze. CONCLUSIONS: Our results support the hypothesis that haze
      after femtosecond LASIK may be a result of damage to the basement membrane and
      Bowman layer of the cornea.

PMID- 22149772
TI  - Reproducibility, validity and predictors of six-minute walk test in overweight
      and obese adolescents with intellectual disability.
AB  - OBJECTIVES: To assess the reproducibility and validity of the six-minute walk
      test (6MWT) and predictors of the six-minute walk distance (6MWD) in adolescents
      with overweight or obesity and intellectual disability (ID). STUDY DESIGN: Sixty
      one adolescents with overweight or obesity and mild-to-moderate ID (intelligent
      quotient [IQ] 40-70; age 14-22 years) participated in this study. To test
      reproducibility, 39 of the participants performed the 6MWT twice with an interval
      of 1 week. To test validity (n = 39), peak oxygen uptake (peak VO(2)) was
      measured on a bicycle ergometer. For the predictor study (n = 61), weight,
      height, peak VO(2) and quadriceps strength were measured, and IQ and orthopedic
      conditions were collected from the participants' medical records. RESULTS: There
      was no significant difference between the means of the two 6MWTs (571.3 vs. 576.5
      m; p = 0.452). The intraclass correlation coefficient was 0.82, indicating good
      reliability. The smallest real difference was 82.6 m. 6MWD correlated
      significantly with relative peak VO(2) (beta = 0.69) indicating validity.
      Relative peak VO(2), height, IQ, body mass index (BMI) and quadriceps strength
      are predictors of the 6MWD in this population. CONCLUSION: 6MWT is a reliable and
      valid test in adolescents with overweight or obesity and ID. Low IQ,
      overweight/obesity and low physical fitness contribute to the outcome of the
      6MWT.

PMID- 22149773
TI  - Coarse-graining entropy, forces, and structures.
AB  - Coarse-grained (CG) models enable highly efficient simulations of complex
      processes that cannot be effectively studied with more detailed models. CG models
      are often parameterized using either force- or structure-motivated approaches.
      The present work investigates parallels between these seemingly divergent
      approaches by examining the relative entropy and multiscale coarse-graining (MS
      CG) methods. We demonstrate that both approaches can be expressed in terms of an
      information function that discriminates between the ensembles generated by
      atomistic and CG models. While it is well known that the relative entropy
      approach minimizes the average of this information function, the present work
      demonstrates that the MS-CG method minimizes the average of its gradient squared.
      We generalize previous results by establishing conditions for the uniqueness of
      structure-based potentials and identify similarities with corresponding
      conditions for the uniqueness of MS-CG potentials. We analyze the mapping entropy
      and extend the MS-CG and generalized-Yvon-Born-Green formalisms for more complex
      potentials. Finally, we present numerical calculations that highlight
      similarities and differences between structure- and force-based approaches. We
      demonstrate that both methods obtain identical results, not only for a complete
      basis set, but also for an incomplete harmonic basis set in Cartesian
      coordinates. However, the two methods differ when the incomplete basis set
      includes higher order polynomials of Cartesian coordinates or is expressed as
      functions of curvilinear coordinates.

PMID- 22149774
TI  - Efficient and accurate local single reference correlation methods for high-spin
      open-shell molecules using pair natural orbitals.
AB  - A production level implementation of the high-spin open-shell (spin unrestricted)
      single reference coupled pair, quadratic configuration interaction and coupled
      cluster methods with up to doubly excited determinants in the framework of the
      local pair natural orbital (LPNO) concept is reported. This work is an extension
      of the closed-shell LPNO methods developed earlier [F. Neese, F. Wennmohs, and A.
      Hansen, J. Chem. Phys. 130, 114108 (2009); F. Neese, A. Hansen, and D. G. Liakos,
      J. Chem. Phys. 131, 064103 (2009)]. The internal space is spanned by localized
      orbitals, while the external space for each electron pair is represented by a
      truncated PNO expansion. The laborious integral transformation associated with
      the large number of PNOs becomes feasible through the extensive use of density
      fitting (resolution of the identity (RI)) techniques. Technical complications
      arising for the open-shell case and the use of quasi-restricted orbitals for the
      construction of the reference determinant are discussed in detail. As in the
      closed-shell case, only three cutoff parameters control the average number of
      PNOs per electron pair, the size of the significant pair list, and the number of
      contributing auxiliary basis functions per PNO. The chosen threshold default
      values ensure robustness and the results of the parent canonical methods are
      reproduced to high accuracy. Comprehensive numerical tests on absolute and
      relative energies as well as timings consistently show that the outstanding
      performance of the LPNO methods carries over to the open-shell case with minor
      modifications. Finally, hyperfine couplings calculated with the variational LPNO
      CEPA/1 method, for which a well-defined expectation value type density exists,
      indicate the great potential of the LPNO approach for the efficient calculation
      of molecular properties.

PMID- 22149775
TI  - A pseudopotential-based composite method: the relativistic pseudopotential
      correlation consistent composite approach for molecules containing 4d transition
      metals (Y-Cd).
AB  - The correlation consistent composite approach (ccCA) has proven to be an
      effective first-principles-based composite approach for main group and first-row
      transition metal species. By combining relativistic pseudopotentials and ccCA,
      accurate energetic and thermodynamic data for heavier elements, including
      transition metals, is obtainable. Relativistic pseudopotential ccCA (rp-ccCA) was
      formulated and tested on 25 molecules from the G3/05 set that contain 4p elements
      (Ga-Kr). A 32.5% time savings was obtained using rp-ccCA, relative to ccCA
      employing all-electron basis sets. When implementing rp-ccCA to compute
      dissociation energies and enthalpies of formation for molecules from the 4p
      block, rp-ccCA results in a mean absolute deviation of 0.89 kcal mol(-1) from
      experimental data. rp-ccCA was also applied to a set of 30 4d transition metal
      containing molecules, ranging from diatomics to Mo(CO)(6), and enthalpies of
      formation for these species were obtained with a mean absolute deviation of 2.89
      kcal mol(-1) in comparison to experimental data. Based on quality of the
      experimentally available enthalpies of formation, where the average value of
      reported experimental error bars is 3.43 kcal mol(-1), rp-ccCA is within
      transition metal chemical accuracy for the 4d molecule set. rp-ccCA is a
      pseudopotential-based composite method for transition metals and is shown to
      yield accurate thermodynamic results for molecules containing heavy elements Ga
      Kr and Y-Cd.

PMID- 22149776
TI  - Accurate variational calculations of the ground 2Po(1s22s22p) and excited
      2S(1s22s2p2) and 2Po(1s22s23p) states of singly ionized carbon atom.
AB  - In this article we report accurate nonrelativistic variational calculations of
      the ground and two excited states of C(+) ion. We employ extended and well
      optimized basis sets of all-electron explicitly correlated Gaussians to represent
      the wave functions of the states. The optimization of the basis functions is
      performed with a procedure employing the analytic gradient of the energy with
      respect to the nonlinear parameters of the Gaussians. The calculations explicitly
      include the effects due to the finite nuclear mass. The calculated transition
      energies between the three states are compared to the experimentally derived
      values. Finally, we present expectation values of some small positive and
      negative powers of the interparticle distances and contact densities.

PMID- 22149777
TI  - SF-[2]R12: a spin-adapted explicitly correlated method applicable to arbitrary
      electronic states.
AB  - The [2](R12) method [M. Torheyden and E. F. Valeev, J. Chem. Phys. 131, 171103
      (2009)] is an explicitly correlated perturbative correction that can greatly
      reduce the basis set error of an arbitrary electronic structure method for which
      the two-electron density matrix is available. Here we present a spin-adapted
      variant (denoted as SF-[2](R12)) that is formulated completely in terms of spin
      free quantities. A spin-free cumulant decomposition and multi-reference
      generalized Brillouin condition are used to avoid three-particle reduced density
      matrix completely. The computational complexity of SF-[2](R12) is proportional to
      the sixth power of the system size and is comparable to the cost of the single
      reference MP2-R12 method. The SF-[2](R12) method is shown to decrease greatly the
      basis set error of multi-configurational wave functions.

PMID- 22149778
TI  - Local pair natural orbitals for excited states.
AB  - We explore how in response calculations for excitation energies with wavefunction
      based (e.g., coupled cluster) methods the number of double excitation amplitudes
      can be reduced by means of truncated pair natural orbital (PNO) expansions and
      localized occupied orbitals. Using the CIS(D) approximation as a test model, we
      find that the number of double excitation amplitudes can be reduced dramatically
      with minor impact on the accuracy if the excited state wavefunction is expanded
      in state-specific PNOs generated from an approximate first-order guess
      wavefunction. As for ground states, the PNO truncation error can also for
      excitation energies be controlled by a single threshold related to generalized
      natural occupation numbers. The best performance is found with occupied orbitals
      which are localized by the Pipek-Mezey localization. For a large test set of
      excited states we find with this localization that already a PNO threshold of 10(
      8)-10(-7), corresponding to an average of only 40-80 PNOs per pair, is sufficient
      to keep the PNO truncation error for vertical excitation energies below 0.01 eV.
      This is a significantly more rapid convergence with the number doubles amplitudes
      than in domain-based local response approaches. We demonstrate that the number of
      significant excited state PNOs scales asymptotically linearly with the system
      size in the worst case of completely delocalized excitations and sub-linearly
      whenever the chromophore does not increase with the system size. Moreover, we
      observe that the flexibility of state-specific PNOs to adapt to the character of
      an excitation allows for an almost unbiased treatment of local, delocalized and
      charge transfer excited states.

PMID- 22149779
TI  - Specific quantum mechanical/molecular mechanical capping-potentials for
      biomolecular functional groups.
AB  - We present a series of capping-potentials designed as link atoms to saturate
      dangling bonds at the quantum/classical interface within density functional
      theory-based hybrid QM/MM calculations. We aim at imitating the properties of
      different carbon-carbon bonds by means of monovalent analytic pseudopotentials.
      These effective potentials are optimized such that the perturbations of the
      quantum electronic density are minimized. This optimization is based on a
      stochastic scheme, which helps to avoid local minima trapping. For a series of
      common biomolecular groups, we find capping-potentials that outperform the more
      common hydrogen-capping in view of structural and spectroscopic properties. To
      demonstrate the transferability to complex systems, we also benchmark our
      potentials with a hydrogen-bonded dimer, yielding systematic improvements in
      structural and spectroscopic parameters.

PMID- 22149780
TI  - Fighting the curse of dimensionality in first-principles semiclassical
      calculations: non-local reference states for large number of dimensions.
AB  - Semiclassical methods face numerical challenges as the dimensionality of the
      system increases. In the general context of the theory of differential equations,
      this is known as the "curse of dimensionality." In the present manuscript, we
      apply the recently-introduced multi-coherent states semiclassical initial value
      representation (MC-SC-IVR) approach to extend the applicability of first
      principles semiclassical calculations. The proposed strategy involves the use of
      non-local coherent states with the goal of increasing accuracy in the Fourier
      transforms, and on the other hand, allows for the selection of peaks of different
      frequencies. The ability to filter desired peaks is important for analyzing the
      power spectra of complex systems. The MC-SC-IVR approach allows us to solve a 19
      dimensional test system and to resolve on-the-fly the power spectra of the
      formaldehyde molecule with very few classical trajectories.

PMID- 22149781
TI  - Calculation of chemical potentials of chain molecules by the incremental gauge
      cell method.
AB  - The gauge cell Monte Carlo method is extended to calculations of the incremental
      chemical potentials and free energies of linear chain molecules. The method was
      applied to chains of Lennard-Jones beads with stiff harmonic bonds up to 500
      monomers in length. We show that the suggested method quantitatively reproduces
      the modified Widom particle insertion method of Kumar et al. [S. K. Kumar, I.
      Szleifer, and A. Z. Panagiotopoulos, Phys. Rev. Lett. 66(22), 2935 (1991)], and
      is by an order of magnitude more efficient for long chains in terms of the
      computational time required for the same accuracy of chemical potential
      calculations. The chain increment ansatz, which suggests that the incremental
      chemical potential is independent of the chain length, was tested at different
      temperatures. We confirmed that the ansatz holds only for coils above the theta
      temperature. Special attention is paid to the effects of the magnitude of
      adsorption potential and temperature on the behavior of single chains in
      confinements that are comparable in size with the free chain radius of gyration.
      At sufficiently low temperatures, the dependence of the incremental chemical
      potential on the chain length in wetting pores is superficially similar to a
      capillary condensation isotherm, reflecting monolayer formation following by pore
      volume filling, as the chain length increases. We find that the incremental gauge
      cell method is an accurate and efficient technique for calculations of the free
      energies of chain molecules in bulk systems and nanoconfinements alike. The
      suggested method may find practical applications, such as modeling polymer
      partitioning on porous substrates and dynamics of chain translocation into
      nanopores.

PMID- 22149782
TI  - A data-integrated method for analyzing stochastic biochemical networks.
AB  - Variability and fluctuations among genetically identical cells under uniform
      experimental conditions stem from the stochastic nature of biochemical reactions.
      Understanding network function for endogenous biological systems or designing
      robust synthetic genetic circuits requires accounting for and analyzing this
      variability. Stochasticity in biological networks is usually represented using a
      continuous-time discrete-state Markov formalism, where the chemical master
      equation (CME) and its kinetic Monte Carlo equivalent, the stochastic simulation
      algorithm (SSA), are used. These two representations are computationally
      intractable for many realistic biological problems. Fitting parameters in the
      context of these stochastic models is particularly challenging and has not been
      accomplished for any but very simple systems. In this work, we propose that
      moment equations derived from the CME, when treated appropriately in terms of
      higher order moment contributions, represent a computationally efficient
      framework for estimating the kinetic rate constants of stochastic network models
      and subsequent analysis of their dynamics. To do so, we present a practical data
      derived moment closure method for these equations. In contrast to previous work,
      this method does not rely on any assumptions about the shape of the stochastic
      distributions or a functional relationship among their moments. We use this
      method to analyze a stochastic model of a biological oscillator and demonstrate
      its accuracy through excellent agreement with CME/SSA calculations. By coupling
      this moment-closure method with a parameter search procedure, we further
      demonstrate how a model's kinetic parameters can be iteratively determined in
      order to fit measured distribution data.

PMID- 22149783
TI  - Thinking outside the box: the uniform electron gas on a hypersphere.
AB  - We discuss alternative homogeneous electron gas systems in which a finite number
      n of electrons are confined to a D-dimensional sphere. We derive the first few
      terms of the high-density (r(s) -> 0, where r(s) is the Seitz radius) energy
      expansions for these systems and show that, in the thermodynamic limit (n ->
      infinity), these terms become identical to those of D-dimensional jellium.

PMID- 22149784
TI  - Structural dynamics of surfaces by ultrafast electron crystallography:
      experimental and multiple scattering theory.
AB  - Recent studies in ultrafast electron crystallography (UEC) using a reflection
      diffraction geometry have enabled the investigation of a wide range of phenomena
      on the femtosecond and picosecond time scales. In all these studies, the analysis
      of the diffraction patterns and their temporal change after excitation was
      performed within the kinematical scattering theory. In this contribution, we
      address the question, to what extent dynamical scattering effects have to be
      included in order to obtain quantitative information about structural dynamics.
      We discuss different scattering regimes and provide diffraction maps that
      describe all essential features of scatterings and observables. The effects are
      quantified by dynamical scattering simulations and examined by direct comparison
      to the results of ultrafast electron diffraction experiments on an in situ
      prepared Ni(100) surface, for which structural dynamics can be well described by
      a two-temperature model. We also report calculations for graphite surfaces. The
      theoretical framework provided here allows for further UEC studies of surfaces
      especially at larger penetration depths and for those of heavy-atom materials.

PMID- 22149785
TI  - Multistage Zeeman deceleration of metastable neon.
AB  - A supersonic beam of metastable neon atoms has been decelerated by exploiting the
      interaction between the magnetic moment of the atoms and time-dependent
      inhomogeneous magnetic fields in a multistage Zeeman decelerator. Using 91
      deceleration solenoids, the atoms were decelerated from an initial velocity of
      580 m/s to final velocities as low as 105 m/s, corresponding to a removal of more
      than 95% of their initial kinetic energy. The phase-space distribution of the
      cold, decelerated atoms was characterized by time-of-flight and imaging
      measurements, from which a temperature of 10 mK was obtained in the moving frame
      of the decelerated sample. In combination with particle-trajectory simulations,
      these measurements allowed the phase-space acceptance of the decelerator to be
      quantified. The degree of isotope separation that can be achieved by multistage
      Zeeman deceleration was also studied by performing experiments with pulse
      sequences generated for (20)Ne and (22)Ne.

PMID- 22149786
TI  - Effect of microhydration on the guanidinium...benzene interaction.
AB  - The effect of microhydration on the interaction of guanidinium cation with
      benzene has been studied by employing ab initio calculations. Four different
      structural arrangements were considered for the guanidinium...benzene interaction
      to which up to six water molecules were added. T-shaped structures are usually
      the most stable, but as water molecules are included the energy differences with
      the parallel structures decrease, reaching a point where parallel complexes are
      even more stable than T-shaped ones. Therefore, the inclusion of water molecules
      promotes a change in the structure of the cation...pi contact. The analysis
      reveals that these stability changes are more related with the structure of the
      hydrating water molecules than to a modulation of the cation...pi interaction.
      Already with three water molecules, one water molecule in the T-shaped complex
      has to be located in the second solvation shell, whereas in parallel structures
      this occurs with four water molecules. As a consequence energy differences among
      structures decrease. The calculations show that the nature of the interaction is
      almost unaffected in T-shaped structures, whereas an important dispersion
      increment is observed in parallel ones, though its overall effect is small.

PMID- 22149787
TI  - Influence of higher-order dispersion coefficients on near-threshold bound and
      continuum states: application to 88Sr2.
AB  - We give a simple description of quantum states near the dissociation threshold of
      deep interatomic potentials. The influence of the potential tail is separated
      from effects due to the interaction at short distances. We present a general
      formalism which is valid for weakly bound and low-energy continuum states, both
      for vanishing and non-vanishing angular momentum. Its applicability is
      demonstrated for the example of the electronic ground state of the strontium
      dimer (88)Sr(2). With an appropriate choice of the potential tail that includes
      higher-order dispersion coefficients, all short-range effects are incorporated
      via the threshold quantum number nu(D) and one further parameter accounting for
      residual short-range effects.

PMID- 22149788
TI  - Vibrational frequencies and spectroscopic constants from quartic force fields for
      cis-HOCO: the radical and the anion.
AB  - The use of accurate quartic force fields together with vibrational configuration
      interaction recently predicted gas phase fundamental vibrational frequencies of
      the trans-HOCO radical to within 4 cm(-1) of experimental results for the two
      highest frequency modes. Utilizing the same approach, we are providing a full
      list of fundamental vibrational frequencies and spectroscopic constants for the
      cis-HOCO system in both radical and anionic forms. Our predicted geometrical
      parameters of the cis-HOCO radical match experiment and previous computation to
      better than 1% deviation, and previous theoretical work agrees equally well for
      the anion. Correspondence between vibrational perturbation theory and variational
      vibrational configuration interaction for prediction of the frequencies of each
      mode is strong, better than 5 cm(-1), except for the torsional motion, similar to
      what has been previously identified in the trans-HOCO radical. Among other
      considerations, our results are immediately applicable to dissociative
      photodetachment experiments which initially draw on the cis-HOCO anion since it
      is the most stable conformer of the anion and is used to gain insight into the
      portion of the OH + CO potential surface where the HOCO radical is believed to
      form, and we are also providing highly accurate electron binding energies
      relevant to these experiments.

PMID- 22149789
TI  - The electronic spectrum of SiH4: Jahn-Teller Rydberg series.
AB  - The aim of the present theoretical work is to provide data necessary for a better
      understanding of the electronic spectrum of the silane molecule, which is
      affected by the Jahn-Teller effect. By selecting an adequate distorted C(2v)
      geometry of SiH(4), the three lower Koopmans ionization potentials are evaluated
      with the equation of motion coupled cluster of singles and doubles method.
      Vertical excitation energies for the different Rydberg series converging to the
      three Jahn-Teller components are inferred from ab initio coupled cluster linear
      response calculations. Absorption oscillator strengths for dipole-allowed
      electronic transitions are also determined with the molecular-adapted quantum
      defect orbital methodology. Predictions of new spectroscopic data on SiH(4) are
      reported.

PMID- 22149790
TI  - Confirmed assignments of isomeric dimethylbenzyl radicals generated by corona
      discharge.
AB  - The controversial vibronic assignments of isomeric dimethylbenzyl radicals were
      clearly resolved by using different precursors. By employing corresponding
      dimethylbenzyl chlorides as precursors, we identified the origins of the vibronic
      bands of the dimethylbenzyl radicals generated by corona discharge of 1,2,4
      trimethylbenzene. From the analysis of the spectra observed from the
      dimethylbenzyl chlorides in a corona excited supersonic expansion, we revised
      previous assignments of the 3,4-, 2,4-, and 2,5-dimethylbenzyl radicals.
      Spectroscopic data of electronic transition and vibrational mode frequencies in
      the ground electronic state of each isomer were accurately determined by
      comparing them with those obtained by an ab initio calculation and with the known
      vibrational data of 1,2,4-trimethylbenzene.

PMID- 22149791
TI  - Heavy atom nitroxyl radicals. V. An experimental and ab initio study of the
      previously unknown H2PS free radical.
AB  - The B(2)A(')-X(2)A(') transition of the prototypical thiophosphoryl radical,
      H(2)PS, was observed for the first time using laser-induced fluorescence and
      single vibronic level emission spectroscopy. H(2)PS and its deuterated
      isotopologues, D(2)PS and HDPS, were produced in a pulsed supersonic discharge
      jet from a precursor mixture of Cl(3)PS and H(2) or D(2) or an H(2)/D(2) mixture
      in high-pressure argon. High level ab initio calculations of the lowest three
      doublet electronic states helped in the definitive assignment of the B-X
      transition, which involves electron promotion from the pi to the pi* orbital.
      Vibrational frequencies were determined for several modes of each isotopologue in
      the X and B states and found to be in accord with theoretical predictions.
      Although a line-by-line rotational analysis was not possible, the observed band
      contours are consistent with the geometries obtained from our ab initio
      calculations. Theory indicates that PS bond length increases upon electronic
      excitation, while the pyramidalization of the radical does not change
      significantly.

PMID- 22149792
TI  - Heavy atom nitroxyl radicals. VI. The electronic spectrum of jet-cooled H2PO, the
      prototypical phosphoryl free radical.
AB  - The previously unknown electronic spectrum of the H(2)PO free radical has been
      identified in the 407-337 nm region using a combination of laser-induced
      fluorescence and single vibronic level emission spectroscopy. High level ab
      initio predictions of the properties of the ground and first two excited doublet
      states were used to identify the spectral region in which to search for the
      electronic transition and were used to aid in the analysis of the data. The band
      system is assigned as the B(2)A(')-X(2)A(') electronic transition which involves
      promotion of an electron from the pi to the pi* molecular orbital. The excited
      state r(0) molecular structure was determined by rotational analysis of high
      resolution LIF spectra to be r(PO) = 1.6710(2) A, r(PH) = 1.4280(6) A, theta(HPO)
      = 105.68(7) degrees , theta(HPH) = 93.3(2) degrees , and the out-of-plane angle =
      66.8(2) degrees . The structural changes on electronic excitation, which include
      substantial increases in the PO bond length and out-of-plane angle, are as
      expected based on molecular orbital theory and our previous studies of the
      isoelectronic H(2)AsO, Cl(2)PS, and F(2)PS free radicals.

PMID- 22149793
TI  - Studies on the structure, stability, and spectral signatures of hydride ion-water
      clusters.
AB  - The gas-phase structure, stability, spectra, and electron density topography of
      H(-)W(n) clusters (where n = 1-8) have been calculated using coupled-cluster
      CCSD(T) and Moller-Plesset second-order perturbation (MP2) theory combined with
      complete basis set (CBS) approaches. The performance of various density
      functional theory (DFT) based methods such as B3LYP, M05-2X, M06, M06-L, and M06
      2X using 6-311++G(d,p), and aug-cc-pVXZ (aVXZ, where X = D, T, and Q) basis sets
      has also been assessed by considering values calculated using CCSD(T)/CBS limit
      as reference. The performance of the functionals has been ranked based on the
      mean signed/unsigned error. The comparison of geometrical parameters elicits that
      the geometrical parameters predicted by B3LYP/aVTZ method are in good agreement
      with those values obtained at MP2/aVTZ level of theory. Results show that M05-2X
      functional outperform other functionals in predicting the energetics when
      compared to CCSD(T)/CBS value. On the other hand, values predicted by M06-2X, and
      M06 methods, are closer to those values obtained from MP2/CBS approach. It is
      evident from the calculations that H(-)W(n) (where n = 5-8) clusters adopt
      several interesting structural motifs such as pyramidal, prism, book, Clessidra,
      cubic, cage, and bag. The important role played by ion-water (O-H...H(-)) and
      water-water (O-H...O) interactions in determining the stability of the clusters
      has also been observed. Analysis of the results indicates that the most stable
      cluster is made up of minimum number of O-H...H(-) interaction in conjugation
      with the maximum number of O-H...O interactions. The Bader theory of atoms in
      molecules (AIM) and natural bond orbital (NBO) analyses has also been carried out
      to characterize the nature of interactions between hydride ion and water
      molecules. It can be observed from the vibrational spectra of H(-)W(n) clusters,
      the stretching frequencies involving ion-water interaction always exhibit larger
      redshift and intensities than that of water-water (inter solvent) interactions.

PMID- 22149794
TI  - Dissociative electron attachment to triflates.
AB  - Gas phase studies of dissociative electron attachment to simple alkyl
      (CF(3)SO(3)CH(3)) and aryl (C(6)H(5)SO(3)CF(3) and CF(3)SO(3)C(6)H(4)CH(3))
      triflates, model molecules of nonionic photoacid generators for modern
      lithographic applications, were performed. The fragmentation pathways under
      electron impact below 10 eV were identified by means of crossed electron
      molecular beam mass spectrometry. Major dissociation channels involved C-O, S-O,
      or C-S bond scissions in the triflate moiety leading to the formation of triflate
      (OTf(-)), triflyl (Tf(-)), or sulfonate (RSO(3)(-)) anions, respectively. A
      resonance leading to C-O bond breakage and OTf(-) formation in alkyl triflates
      occurred at electron energies about 0.5 eV lower than the corresponding resonance
      in aryl triflates. A resonance leading to S-O bond breakage and Tf(-) formation
      in aryl triflates occurred surprisingly at the same electron energies as C-O bond
      breakage. In case of alkyl triflates S-O bond breakage required 1.4 eV higher
      electron energies to occur and proceeded with substantially lower yields than in
      aryl triflates. C-S bond scission occurred for all presently studied triflates at
      energies close to 3 eV.

PMID- 22149795
TI  - Competitive ionization processes of anthracene excited with a femtosecond pulse
      in the multi-photon ionization regime.
AB  - To clarify the ionization mechanism of large molecules under multi-photon
      ionization conditions, photo-electron spectroscopic studies on anthracene have
      been performed with electron imaging technique. Electron kinetic energy
      distributions below a few eV reveal that three kinds of ionization channels
      coexist, viz., vertical ionization, ionization from Rydberg states, and
      thermionic hot electron emission. Their relative yield is determined by the
      characteristic of the laser pulse. The duration in particular influences the
      ratio between the first two processes, while for higher intensities the last
      process dominates. Our results provide strong evidence that internal conversion
      plays an important role for the ionization of the molecule.

PMID- 22149796
TI  - On the effects of high temperature and high pressure on the hydrogen solubility
      in rhenium.
AB  - In situ x-ray diffraction experiments on rhenium hydride compressed up to 46 GPa
      reveal a hydrogen solubility (x) significantly larger than the previously assumed
      saturation limit of x ~ 0.38(4). In the layered anti-CdI(2)-type structure of
      rhenium hydride, the hydrogen solubility was found to increase to x ~ 0.5 at 15
      GPa over time. When heated to temperatures above 420 K at pressures above 23 GPa,
      rhenium hydride undergoes an isomorphous phase transition into the NiAs-type
      structure accompanied by an increase in hydrogen solubility to x ~ 0.85. The
      formation of fully stoichiometric rhenium hydride is discussed.

PMID- 22149797
TI  - Topological origin of stretched exponential relaxation in glass.
AB  - The physical origin of stretched exponential relaxation is considered by many as
      one of the oldest unsolved problems in science. The functional form for stretched
      exponential relaxation can be deduced from the axiomatic diffusion-trap model of
      Phillips. The model predicts a topological origin for the dimensionless
      stretching exponent, with two "magic" values emerging: beta = 3/5 arising from
      short-range molecular relaxation pathways and beta = 3/7 for relaxation dominated
      by longer-range interactions. In this paper, we report experimental confirmation
      of these values using microscopically homogeneous silicate glass specimens. Our
      results reveal a bifurcation of the stretching exponent, with beta = 3/5 for
      stress relaxation and beta = 3/7 for structural relaxation, both on macroscopic
      length scales. These results point to two fundamentally different mechanisms
      governing stress relaxation versus structural relaxation, corresponding to
      different effective dimensionalities in configuration space during the relaxation
      process.

PMID- 22149798
TI  - Manifestations of probe presence on probe dynamics in supercooled liquids.
AB  - Experimental studies that follow behavior of single probes embedded in
      heterogeneous systems are increasingly common. The presence of probes may perturb
      the system, and such perturbations may or may not affect interpretation of host
      behavior from the probe observables typically measured. In this study, the
      manifestations of potential probe-induced changes to host dynamics in supercooled
      liquids are investigated via molecular dynamics simulations. It is found that
      probe dynamics do not necessarily mirror host dynamics as they exist either in
      the probe-free or probe-bearing systems. In particular, for a binary supercooled
      liquid, we find that smooth probes larger than the host particles induce
      increased translational diffusion in the host system; however, the diffusion is
      anisotropic and enhances caging of the probe, suppressing probe translational
      diffusion. This in turn may lead experiments that follow probe diffusion to
      suggest Stokes-Einstein behavior of the system even while both the probe-free and
      probe-bearing systems exhibit deviations from that behavior.

PMID- 22149799
TI  - Redistribution of carbonyl stretch mode energy in isolated and solvated N
      methylacetamide: kinetic energy spectral density analyses.
AB  - The vibrational energy transfer from the excited carbonyl stretch mode in N
      deuterated N-methylacetamide (NMA-d), both in isolation and in a heavy water
      cluster, is studied with nonequilibrium molecular dynamics (NEMD) simulations,
      employing a quantum mechanical/molecular mechanical (QM/MM) force field at the
      semiempirical PM3 level. The nonequilibrium ensemble of vibrationally excited NMA
      d is prepared by perturbing the positions and velocities of the carbonyl C and O
      atoms and its NEMD trajectories are obtained with a leap-frog algorithm properly
      modified for the initial perturbation. In addition to the time-domain analysis of
      the kinetic and potential energies, a novel method for the spectral analysis of
      the atomic kinetic energies is developed, in terms of the spectral density of
      kinetic energy, which provides the time-dependent changes of the frequency
      resolved kinetic energies without the complications of normal mode analysis at
      every MD time step. Due to the QM description of the solute electronic structure,
      the couplings among the normal modes are captured more realistically than with
      classical force fields. The energy transfer in the isolated NMA-d is found to
      proceed first from the carbonyl bond to other modes with time scales of 3 ps or
      less, and then among the other modes over 3-21 ps. In the solvated NMA-d, most of
      the excess energy is first transferred to other intramolecular modes within 5 ps,
      which is subsequently dissipated to solvent with 7-19 ps time scales. The
      contribution of the direct energy transfer from the carbonyl bond to solvent was
      only 5% with ~7 ps time scale. Solvent reorganization that leads to
      destabilization of the electrostatic interactions is found to be crucial in the
      long time relaxation of the excess energy, while the water intramolecular modes
      do not contribute significantly. Detailed mode-specific energy transfer pathways
      are deduced for the isolated and solvated NMA-d and they show that the energy
      transfer in NMA-d is a highly cooperative process among the intramolecular modes
      and there is no single dominant pathway with more than 30% of transient
      contribution.

PMID- 22149800
TI  - Analyzing mechanisms and microscopic reversibility of self-assembly.
AB  - We use computer simulations to investigate self-assembly in a system of model
      chaperonin proteins, and in an Ising lattice gas. We discuss the mechanisms
      responsible for rapid and efficient assembly in these systems, and we use
      measurements of dynamical activity and assembly progress to compare their
      propensities for kinetic trapping. We use the analytic solution of a simple
      minimal model to illustrate the key features associated with such trapping,
      paying particular attention to the number of ways that particles can misbind. We
      discuss the relevance of our results for the design and control of self-assembly
      in general.

PMID- 22149801
TI  - The tautomerization phenomenon of glibenclamide drug monitored by means of
      volumetric measurements.
AB  - In this paper, we investigate the tautomerization process of glibenclamide drug
      by monitoring the changes in the specific volume. The density changes observed
      during the chemical equilibration process, carried out at a pressure of p = 10
      MPa and at three different temperatures, enable us to study the kinetics of
      tautomerization reaction, i.e., to determine the activation energy and to
      recognize the real time scale of this process at various temperature conditions.
      The results obtained from analysis of V(sp)(t) dependencies were next compared
      with the kinetic data previously obtained from dielectric spectroscopy studies.

PMID- 22149802
TI  - Thermal properties of ionic systems near the liquid-liquid critical point.
AB  - Isobaric heat capacity per unit volume, C(p), and excess molar enthalpy, h(E),
      were determined in the vicinity of the critical point for a set of binary systems
      formed by an ionic liquid and a molecular solvent. Moreover, and, since critical
      composition had to be accurately determined, liquid-liquid equilibrium curves
      were also obtained using a calorimetric method. The systems were selected with a
      view on representing, near room temperature, examples from clearly solvophobic to
      clearly coulombic behavior, which traditionally was related with the electric
      permittivity of the solvent. The chosen molecular compounds are: ethanol, 1
      butanol, 1-hexanol, 1,3-dichloropropane, and diethylcarbonate, whereas ionic
      liquids are formed by imidazolium-based cations and tetrafluoroborate or bis
      (trifluromethylsulfonyl)amide anions. The results reveal that solvophobic
      critical behavior-systems with molecular solvents of high dielectric permittivity
      is very similar to that found for molecular binary systems. However, coulombic
      systems-those with low permittivity molecular solvents-show strong deviations
      from the results usually found for these magnitudes near the liquid-liquid phase
      transition. They present an extremely small critical anomaly in C(p)-several
      orders of magnitude lower than those typically obtained for binary mixtures-and
      extremely low h(E)-for one system even negative, fact not observed, up to date,
      for any liquid-liquid transition in the nearness of an upper critical solution
      temperature.

PMID- 22149803
TI  - The dependence of singlet exciton relaxation on excitation density and
      temperature in polycrystalline tetracene thin films: kinetic evidence for a dark
      intermediate state and implications for singlet fission.
AB  - The excited state dynamics of polycrystalline tetracene films are studied using
      femtosecond transient absorption in combination with picosecond fluorescence,
      continuing work reported in an earlier paper [J. J. Burdett, A. M. Muller, D.
      Gosztola, and C. J. Bardeen, J. Chem. Phys. 133, 144506 (2010)]. A study of the
      intensity dependence of the singlet state decay is conducted to understand the
      origins of the discrepancy between the broadband transient absorption and
      fluorescence experiments seen previously. High-sensitivity single channel
      transient absorption experiments allow us to compare the transient absorption
      dynamics to the fluorescence dynamics measured at identical laser fluences. At
      high excitation densities, an exciton-exciton annihilation rate constant of ~1 *
      10(-8) cm(3) s(-1) leads to rapid singlet decays, but at excitation densities of
      2 * 10(17) cm(-3) or less the kinetics of the transient absorption match those of
      the fluorescence. At these lower excitation densities, both measurements confirm
      that the initially excited singlet state relaxes with a decay time of 80 +/- 3
      ps, not 9.2 ps as claimed in the earlier paper. In order to investigate the
      origin of the singlet decay, the wavelength-resolved fluorescence dynamics were
      measured at 298 K, 77 K, and 4 K. A high-energy J-type emitting species undergo a
      rapid (~100 ps) decay at all temperatures, while at 77 K and 4 K additional
      species with H-type and J-type emission lineshapes have much longer lifetimes. A
      global analysis of the wavelength-dependent decays shows that the initial ~100 ps
      decay occurs to a dark state and not via energy transfer to lower energy bright
      states. Varying the excitation wavelength from 400 nm to 510 nm had no effect on
      the fast decay, suggesting that there is no energy threshold for the initial
      singlet relaxation. The presence of different emitting species at different
      temperatures means that earlier interpretations of the fluorescence behavior in
      terms of one singlet state that is short-lived due to singlet fission at high
      temperatures but long-lived at lower temperatures are probably too simplistic.
      The presence of a rapid singlet decay at all temperatures indicates that the
      initially created J-type singlet exciton decays to an intermediate that only
      produces free triplets (and delayed fluorescence) at high temperatures.

PMID- 22149804
TI  - Vibrational dynamics of the bending mode of water interacting with ions.
AB  - We studied the vibrational relaxation dynamics of the bending mode (nu(2)) of the
      H(2)O water molecules in the presence of different salts (LiCl, LiBr, LiI, NaI,
      CsI, NaClO(4), and NaBF(4)). The linear and nonlinear spectra of the bending mode
      show distinct responses of water molecules hydrating the anions. We observe that
      the bending mode of water molecules that are hydrogen-bonded to an anion exhibits
      much slower relaxation rates (T(1)~1ps) than water molecules that are hydrogen
      bonded to other water molecules (T(1)=400 fs). We find that the effect of the
      anion on the absorption spectrum and relaxation time constant of the water
      bending mode is not only determined by the strength of the hydrogen-bond
      interaction but also by the shape of the anion.

PMID- 22149805
TI  - Influence of quantum effects on the physisorption of molecular hydrogen in model
      carbon foams.
AB  - The physisorption of molecular hydrogen in model carbon foams has been
      investigated from 50 K to room temperature. The study is carried out within the
      framework of the density functional theory for quantum liquids at finite
      temperatures. Calculations are performed in the grand canonical ensemble, i.e.,
      the adsorbed fluid is assumed to be in equilibrium with an external gas of
      hydrogen molecules with concentrations ranging from 8*10(-4) kg m(-3) to n=71 kg
      m(-3). It is shown that, while strong zero-point energy effects are present even
      at room temperature, the adsorption isotherms exhibit only a weak dependence on
      the explicit incorporation of the bosonic exchange symmetry of hydrogen
      molecules. The increase of the average particle density prevents the deviations
      from the Maxwell-Boltzmann statistics to become noticeable if the system is
      cooled down. The volumetric storage capacity of these materials at low
      temperatures is about one half of the U. S. Department of Energy goal, while the
      gravimetric capacity is still far from the standards required by mobile
      applications. The relation between the microscopic structure of the hydrogen
      fluid and the calculated adsorption properties is also addressed.

PMID- 22149806
TI  - First principles study of adsorption of O2 on Al surface with hybrid functionals.
AB  - Adsorption of O(2) molecule on Al surface has been a long standing puzzle for the
      first principles calculation. We have studied the adsorption of O(2) molecule on
      the Al(111) surface using hybrid functionals. In contrast to the previous local
      density approximation/gradient-corrected approximation, the present calculations
      with hybrid functionals successfully predict that O(2) molecule can be absorbed
      on the Al(111) surface with a barrier around 0.2-0.4 eV, which is in good
      agreement with experiments. Our calculations predict that the lowest unoccupied
      molecular orbital of O(2) molecule is higher than the Fermi level of the Al(111)
      surface, which is responsible for the barrier of the O(2) adsorption.

PMID- 22149807
TI  - Statics of polymer droplets on deformable surfaces.
AB  - The equilibrium properties of polymer droplets on a soft deformable surface are
      investigated by molecular dynamics simulations of a bead-spring model. The
      surface consists of a polymer brush with irreversibly end-tethered linear
      homopolymer chains onto a flat solid substrate. We tune the softness of the
      surface by varying the grafting density. Droplets are comprised of bead-spring
      polymers of various chain lengths. First, both systems, brush and polymer liquid,
      are studied independently in order to determine their static and dynamic
      properties. In particular, using a numerical implementation of an AFM experiment,
      we measure the shear modulus of the brush surface and compare the results to
      theoretical predictions. Then, we study the wetting behavior of polymer droplets
      with different surface/drop compatibility and on substrates that differ in
      softness. Density profiles reveal, under certain conditions, the formation of a
      wetting ridge beneath the three-phase contact line. Cap-shaped droplets and
      cylindrical droplets are also compared to estimate the effect of the line tension
      with respect to the droplet size. Finally, the results of the simulations are
      compared to a phenomenological free-energy calculation that accounts for the
      surface tensions and the compliance of the soft substrate. Depending on the
      surface/drop compatibility, surface softness, and drop size, a transition between
      two regimes is observed: from one where the drop surface energy balances the
      adhesion with the surface, which is the classical Young-Dupre wetting regime, to
      another one where a coupling occurs between adhesion, droplet and surface elastic
      energies.

PMID- 22149808
TI  - Electrical conductivity in Li2O2 and its role in determining capacity limitations
      in non-aqueous Li-O2 batteries.
AB  - Non-aqueous Li-air or Li-O(2) cells show considerable promise as a very high
      energy density battery couple. Such cells, however, show sudden death at
      capacities far below their theoretical capacity and this, among other problems,
      limits their practicality. In this paper, we show that this sudden death arises
      from limited charge transport through the growing Li(2)O(2) film to the Li(2)O(2)
      electrolyte interface, and this limitation defines a critical film thickness,
      above which it is not possible to support electrochemistry at the Li(2)O(2)
      electrolyte interface. We report both electrochemical experiments using a
      reversible internal redox couple and a first principles metal-insulator-metal
      charge transport model to probe the electrical conductivity through Li(2)O(2)
      films produced during Li-O(2) discharge. Both experiment and theory show a
      "sudden death" in charge transport when film thickness is ~5 to 10 nm. The
      theoretical model shows that this occurs when the tunneling current through the
      film can no longer support the electrochemical current. Thus, engineering charge
      transport through Li(2)O(2) is a serious challenge if Li-O(2) batteries are ever
      to reach their potential.

PMID- 22149809
TI  - Capillary filling with giant liquid/solid slip: dynamics of water uptake by
      carbon nanotubes.
AB  - This article discusses the way the standard description of capillary filling
      dynamics has to be modified to account for liquid/solid slip in nanometric pores.
      It focuses, in particular, on the case of a large slip length compared to the
      pore size. It is shown that the liquid viscosity does not play a role, and that
      the flow is only controlled by the friction coefficient of the liquid at the
      wall. Moreover, in the Washburn regime, the filling velocity does not depend on
      the tube radius. Finally, molecular dynamics simulations suggest that this
      standard description fails to describe the early stage of capillary filling of
      carbon nanotubes by water, since viscous dissipation at the tube entrance must be
      taken into account.

PMID- 22149810
TI  - Sedimentation of a charged colloidal sphere in a charged cavity.
AB  - An analytical study is presented for the quasisteady sedimentation of a charged
      spherical particle located at the center of a charged spherical cavity. The
      overlap of the electric double layers is allowed, and the polarization
      (relaxation) effect in the double layers is considered. The electrokinetic
      equations that govern the ionic concentration distributions, electric potential
      profile, and fluid flow field in the electrolyte solution are linearized assuming
      that the system is only slightly distorted from equilibrium. Using a perturbation
      method, these linearized equations are solved for a symmetric electrolyte with
      the surface charge densities of the particle and cavity as the small perturbation
      parameters. An analytical expression for the settling velocity of the charged
      sphere is obtained from a balance among the gravitational, electrostatic, and
      hydrodynamic forces acting on it. Our results indicate that the presence of the
      particle charge reduces the magnitude of the sedimentation velocity of the
      particle in an uncharged cavity and the presence of the fixed charge at the
      cavity surface increases the magnitude of the sedimentation velocity of an
      uncharged particle in a charged cavity. For the case of a charged sphere settling
      in a charged cavity with equivalent surface charge densities, the net effect of
      the fixed charges will increase the sedimentation velocity of the particle. For
      the case of a charged sphere settling in a charged cavity with their surface
      charge densities in opposite signs, the net effect of the fixed charges in
      general reduces/increases the sedimentation velocity of the particle if the
      surface charge density of the particle has a greater/smaller magnitude than that
      of the cavity. The effect of the surface charge at the cavity wall on the
      sedimentation of a colloidal particle is found to increase with a decrease in the
      particle-to-cavity size ratio and can be significant in appropriate situations.

PMID- 22149811
TI  - Solvent response of mixed polymer brushes.
AB  - We have performed classical density functional theory calculations to study the
      behavior of mixed polymer brushes tethered to a planar surface. We assume no
      lateral segregation of the polymer at the grafting density studied and consider
      an implicit solvent. For a binary mixture of short and long athermal polymer
      chains, the short chain is compressed while the long chain is stretched compared
      with corresponding pure polymer chains at the same grafting density, which is
      consistent with simulation. This results from configurational entropy effects.
      Furthermore, we add a mean-field interaction for each polymer brush to simulate
      their different response towards a solvent. The long chain is forced to dislike
      the solvent more than the short chain. Through the interplay between the solvent
      effects and configurational entropy effects, a switch of the polymer brush
      surface (or outer) layer is found with increasing chain length of the long chain.
      The transition chain length (long chain) increases with increasing the solvent
      selectivity, and decreases with increasing the grafting density of the long
      chain. These results can provide guidance for the design of smart materials based
      on mixed polymer brushes.

PMID- 22149812
TI  - Interactions between polymer brush-coated spherical nanoparticles: the good
      solvent case.
AB  - The interaction between two spherical polymer brushes is studied by molecular
      dynamics simulation varying both the radius of the spherical particles and their
      distance, as well as the grafting density and the chain length of the end-grafted
      flexible polymer chains. A coarse-grained bead-spring model is used to describe
      the macromolecules, and purely repulsive monomer-monomer interactions are taken
      throughout, restricting the study to the good solvent limit. Both the potential
      of mean force between the particles as a function of their distance is computed,
      for various choices of the parameters mentioned above, and the structural
      characteristics are discussed (density profiles, average end-to-end distance of
      the grafted chains, etc.). When the nanoparticles approach very closely, some
      chains need to be squeezed out into the tangent plane in between the particles,
      causing a very steep rise of the repulsive interaction energy between the
      particles. We consider as a complementary method the density functional theory
      approach. We find that the quantitative accuracy of the density functional theory
      is limited to large nanoparticle separation and short chain length. A brief
      comparison to Flory theory and related work on other models also is presented.

PMID- 22149813
TI  - A coarse-grained model for polyethylene glycol polymer.
AB  - A coarse-grained (CG) model of polyethylene glycol (PEG) was developed and
      implemented in CG molecular dynamics (MD) simulations of PEG chains with degree
      of polymerization (DP) 20 and 40. In the model, two repeat units of PEG are
      grouped as one CG bead. Atomistic MD simulation of PEG chains with DP = 20 was
      first conducted to obtain the bonded structural probability distribution
      functions (PDFs) and nonbonded pair correlation function (PCF) of the CG beads.
      The bonded CG potentials are obtained by simple inversion of the corresponding
      PDFs. The CG nonbonded potential is parameterized to the PCF using both an
      inversion procedure based on the Ornstein-Zernike equation with the Percus-Yevick
      approximation (OZPY(-1)) and a combination of OZPY(-1) with the iterative
      Boltzmann inversion (IBI) method (OZPY(-1)+IBI). As a simple one step method, the
      OZPY(-1) method possesses an advantage in computational efficiency. Using the
      potential from OZPY(-1) as an initial guess, the IBI method shows fast
      convergence. The coarse-grained molecular dynamics (CGMD) simulations of PEG
      chains with DP = 20 using potentials from both methods satisfactorily reproduce
      the structural properties from atomistic MD simulation of the same systems. The
      OZPY(-1)+IBI method yields better agreement than the OZPY(-1) method alone. The
      new CG model and CG potentials from OZPY(-1)+IBI method was further tested
      through CGMD simulation of PEG with DP = 40 system. No significant changes are
      observed in the comparison of PCFs from CGMD simulations of PEG with DP = 20 and
      40 systems indicating that the potential is independent of chain length.

PMID- 22149817
TI  - Tumor hypoxia is an important mechanism of radioresistance in hypofractionated
      radiotherapy and must be considered in the treatment planning process.

PMID- 22149818
TI  - Robust automatic segmentation of multiple implanted cylindrical gold fiducial
      markers in cone-beam CT projections.
AB  - PURPOSE: Implanted fiducial markers, which are used to correct for day-to-day
      variations, may potentially also be used to correct for intrafraction motion
      measurements. However, before any treatment can make use of, and react to, the
      position of the inserted markers they have to be segmented, either manually
      through expert user intervention or automatically from an imaging system. In the
      current study, we aimed to establish a robust and autonomous segmentation method
      for implanted cylindrical gold markers in a single set of projections from a cone
      beam computed tomography (CBCT). METHODS: Multiple cylindrical gold markers were
      segmented in the projection images of CBCT scans by five sequential steps.
      Initially, marker candidates were identified in all projections with a blob
      detection routine, and then traced in subsequent projections. Traces inconsistent
      with a 3D marker position were rejected, and the best remaining traces were
      identified and used for the construction of a 3D marker constellation model,
      consisting of the size, position and orientation of the markers. Finally,
      projections of the model were used to generate templates for the final template
      based marker segmentation. Hereby, challenging situations such as overlap of
      markers and low contrast regions were taken into account. The segmentation method
      was tested in 63 CBCT scans from 11 patients with 2-4 cylindrical gold markers
      implanted in the prostate and for 62 CBCT scans from six patients each with 2-3
      cylindrical gold markers implanted in the liver and up to two cylindrical markers
      placed externally on the abdomen. After segmentation all projections of the 125
      scans were manually inspected, and a successful segmentation was registered if
      the segmented position was within the projection of the marker. RESULTS: For
      prostate markers, the segmentation was successful in 99.8% of the projections.
      For the liver patients, liver markers and external markers were segmented
      successfully in 99.9 and 99.8% of the projections, respectively. All markers were
      identified in the 3D marker constellation model. The most common source of
      segmentation error was low contrast and motion of markers relative to each other,
      which resulted in a discrepancy between the template and actual projection
      appearance during marker overlap. Markers were overlapping in 20, 2.7, and 0.1%
      of the projections for prostate, liver, and external, respectively. CONCLUSIONS:
      We have successfully implemented a new method that, without prior knowledge on
      marker size, position, orientation, and number, autonomously segments cylindrical
      gold markers from CBCT projections with a high success rate, despite overlap,
      motion, and low contrast.

PMID- 22149819
TI  - Evaluations of an adaptive planning technique incorporating dose feedback in
      image-guided radiotherapy of prostate cancer.
AB  - PURPOSE: Online image guidance (IG) has been used to effectively correct the
      setup error and inter-fraction rigid organ motion for prostate cancer. However,
      planning margins are still necessary to account for uncertainties such as
      deformation and intra-fraction motion. The purpose of this study is to
      investigate the effectiveness of an adaptive planning technique incorporating
      offline dose feedback to manage inter-fraction motion and residuals from online
      correction. METHODS: Repeated helical CT scans from 28 patients were included in
      the study. The contours of prostate and organs-at-risk (OARs) were delineated on
      each CT, and online IG was simulated by matching center-of-mass of prostate
      between treatment CTs and planning CT. A seven beam intensity modulated radiation
      therapy (IMRT) plan was designed for each patient on planning CT for a total of
      15 fractions. Dose distribution at each fraction was evaluated based on actual
      contours of the target and OARs from that fraction. Cumulative dose up to each
      fraction was calculated by tracking each voxel based on a deformable registration
      algorithm. The cumulative dose was compared with the dose from initial plan. If
      the deviation exceeded the pre-defined threshold, such as 2% of the D99 to the
      prostate, an adaptive planning technique called dose compensation was invoked, in
      which the cumulative dose distribution was fed back to the treatment planning
      system and the dose deficit was made up through boost radiation in future
      treatment fractions. The dose compensation was achieved by IMRT inverse planning.
      Two weekly compensation delivery strategies were simulated: one intended to
      deliver the boost dose in all future fractions (schedule A) and the other in the
      following week only (schedule B). The D99 to prostate and generalized equivalent
      uniform dose (gEUD) to rectal wall and bladder were computed and compared with
      those without the dose compensation. RESULTS: If only 2% underdose is allowed at
      the end of the treatment course, then 11 patients fail. If the same criteria is
      assessed at the end of each week (every five fractions), then 14 patients fail,
      with three patients failing the 1st or 2nd week but passing at the end. The
      average dose deficit from these 14 patients was 4.4%. They improved to 2% after
      the weekly compensation. Out of these 14 patients who needed dose compensation,
      ten passed the dose criterion after weekly dose compensation, three patients
      failed marginally, and one patient still failed the criterion significantly (10%
      deficit), representing 3.6% of the patient population. A more aggressive
      compensation frequency (every three fractions) could successfully reduce the dose
      deficit to the acceptable level for this patient. The average number of required
      dose compensation re-planning per patient was 0.82 (0.79) per patient for
      schedule A (B) delivery strategy. The doses to OARs were not significantly
      different from the online IG only plans without dose compensation. CONCLUSIONS:
      We have demonstrated the effectiveness of offline dose compensation technique in
      image-guided radiotherapy for prostate cancer. It can effectively account for
      residual uncertainties which cannot be corrected through online IG. Dose
      compensation allows further margin reduction and critical organs sparing.

PMID- 22149820
TI  - Virtual monochromatic imaging in dual-source dual-energy CT: radiation dose and
      image quality.
AB  - PURPOSE: To evaluate the image quality of virtual monochromatic images
      synthesized from dual-source dual-energy computed tomography (CT) in comparison
      with conventional polychromatic single-energy CT for the same radiation dose.
      METHODS: In dual-energy CT, besides the material-specific information, one may
      also synthesize monochromatic images at different energies, which can be used for
      routine diagnosis similar to conventional polychromatic single-energy images. In
      this work, the authors assessed whether virtual monochromatic images generated
      from dual-source CT scanners had an image quality similar to that of
      polychromatic single-energy images for the same radiation dose. First, the
      authors provided a theoretical analysis of the optimal monochromatic energy for
      either the minimum noise level or the highest iodine contrast to noise ratio
      (CNR) for a given patient size and dose partitioning between the low- and high
      energy scans. Second, the authors performed an experimental study on a dual
      source CT scanner to evaluate the noise and iodine CNR in monochromatic images. A
      thoracic phantom with three sizes of attenuating rings was used to represent four
      adult sizes. For each phantom size, three dose partitionings between the low
      energy (80 kV) and the high-energy (140 kV) scans were used in the dual-energy
      scan. Monochromatic images at eight energies (40 to 110 keV) were generated for
      each scan. Phantoms were also scanned at each of the four polychromatic single
      energy (80, 100, 120, and 140 kV) with the same radiation dose. RESULTS: The
      optimal virtual monochromatic energy depends on several factors: phantom size,
      partitioning of the radiation dose between low- and high-energy scans, and the
      image quality metrics to be optimized. With the increase of phantom size, the
      optimal monochromatic energy increased. With the increased percentage of
      radiation dose on the low energy scan, the optimal monochromatic energy
      decreased. When maximizing the iodine CNR in monochromatic images, the optimal
      energy was lower than that when minimizing noise level. When the total radiation
      dose was equally distributed between low and high energy in dual-energy scans,
      for minimum noise, the optimal energies were 68, 71, 74, and 77 keV for small,
      medium, large, and extra-large (xlarge) phantoms, respectively; for maximum
      iodine CNR, the optimal energies were 66, 68, 70, 72 keV. With the optimal
      monochromatic energy, the noise level was similar to and the CNR was better than
      that in a single-energy scan at 120 kV for the same radiation dose. Compared to
      an 80 kV scan, however, the iodine CNR in monochromatic images was lower for the
      small, medium, and large phantoms. CONCLUSIONS: In dual-source dual-energy CT,
      optimal virtual monochromatic energy depends on patient size, dose partitioning,
      and the image quality metric optimized. With the optimal monochromatic energy,
      the noise level was similar to and the iodine CNR was better than that in 120 kV
      images for the same radiation dose. Compared to single-energy 80 kV images, the
      iodine CNR in virtual monochromatic images was lower for small to large phantom
      sizes.

PMID- 22149821
TI  - An improved model for describing the contrast bolus in perfusion MRI.
AB  - PURPOSE: Quantification of perfusion measurements using dynamic, susceptibility
      weighted contrast-enhanced (DSC) MRI depends on estimating the size and shape of
      the tracer bolus. Typically, the bolus is described as a gamma variate function
      (GV) fitted to the bolus portion of tracer concentration time curve (CTC).
      However, the last point to fit is arbitrary which can lead to considerable
      variation in the fitted curve in the presence of noise. In this technical note,
      we present a model which takes into account recirculation explicitly and fits
      robustly to the entire CTC in the presence of noise. METHODS: Signal data
      measurements from ten DSC MRI patients were fitted with our new model and a GV
      function using four different methods of estimating the end of the bolus.
      Estimates of the area under the curves (AUC) and first moments (FMs) of the bolus
      were compared at different noise levels. RESULTS: The new model gave errors
      similar to or smaller than those of the most effective methods for fitting a GV.
      CONCLUSIONS: The single compartment recirculation (SCR) model is the most robust
      fitting technique with respect to noise both for bias and variability.

PMID- 22149823
TI  - Pitfalls of tungsten multileaf collimator in proton beam therapy.
AB  - PURPOSE: Particle beam therapy is associated with significant startup and
      operational cost. Multileaf collimator (MLC) provides an attractive option to
      improve the efficiency and reduce the treatment cost. A direct transfer of the
      MLC technology from external beam radiation therapy is intuitively
      straightforward to proton therapy. However, activation, neutron production, and
      the associated secondary cancer risk in proton beam should be an important
      consideration which is evaluated. METHODS: Monte Carlo simulation with FLUKA
      particle transport code was applied in this study for a number of treatment
      models. The authors have performed a detailed study of the neutron generation,
      ambient dose equivalent [H*(10)], and activation of a typical tungsten MLC and
      compared with those obtained from a brass aperture used in a typical proton
      therapy system. Brass aperture and tungsten MLC were modeled by absorber blocks
      in this study, representing worst-case scenario of a fully closed collimator.
      RESULTS: With a tungsten MLC, the secondary neutron dose to the patient is at
      least 1.5 times higher than that from a brass aperture. The H*(10) from a
      tungsten MLC at 10 cm downstream is about 22.3 mSv/Gy delivered to water phantom
      by noncollimated 200 MeV beam of 20 cm diameter compared to 14 mSv/Gy for the
      brass aperture. For a 30-fraction treatment course, the activity per unit volume
      in brass aperture reaches 5.3 * 104 Bq cm(-3) at the end of the last treatment.
      The activity in brass decreases by a factor of 380 after 24 h, additional 6.2
      times after 40 days of cooling, and is reduced to background level after 1 yr.
      Initial activity in tungsten after 30 days of treating 30 patients per day is
      about 3.4 times higher than in brass that decreases only by a factor of 2 after
      40 days and accumulates to 1.2 * 106 Bq cm(-3) after a full year of operation.
      The daily utilization of the MLC leads to buildup of activity with time. The
      overall activity continues to increase due to (179)Ta with a half-life of 1.82 yr
      and thus require prolonged storage for activity cooling. The H*(10) near the
      patient side of the tungsten block is about 100 MUSv/h and is 27 times higher at
      the upstream side of the block. This would lead to an accumulated dose for
      therapists in a year that may exceed occupational maximum permissible dose (50
      mSv/yr). The value of H*(10) at the upstream surface of the tungsten block is
      about 220 times higher than that of the brass. CONCLUSIONS: MLC is an efficient
      way for beam shaping and overall cost reduction device in proton therapy.
      However, based on this study, tungsten seems to be not an optimal material for
      MLC in proton beam therapy. Usage of tungsten MLC in clinic may create
      unnecessary risks associated with the secondary neutrons and induced
      radioactivity for patients and staff depending on the patient load. A careful
      selection of material for manufacturing of an optimal MLC for proton therapy is
      thus desired.

PMID- 22149822
TI  - Four-dimensional magnetic resonance imaging (4D-MRI) using image-based
      respiratory surrogate: a feasibility study.
AB  - PURPOSE: Four-dimensional computed tomography (4D-CT) has been widely used in
      radiation therapy to assess patient-specific breathing motion for determining
      individual safety margins. However, it has two major drawbacks: low soft-tissue
      contrast and an excessive imaging dose to the patient. This research aimed to
      develop a clinically feasible four-dimensional magnetic resonance imaging (4D
      MRI) technique to overcome these limitations. METHODS: The proposed 4D-MRI
      technique was achieved by continuously acquiring axial images throughout the
      breathing cycle using fast 2D cine-MR imaging, and then retrospectively sorting
      the images by respiratory phase. The key component of the technique was the use
      of body area (BA) of the axial MR images as an internal respiratory surrogate to
      extract the breathing signal. The validation of the BA surrogate was performed
      using 4D-CT images of 12 cancer patients by comparing the respiratory phases
      determined using the BA method to those determined clinically using the Real-time
      position management (RPM) system. The feasibility of the 4D-MRI technique was
      tested on a dynamic motion phantom, the 4D extended Cardiac Torso (XCAT) digital
      phantom, and two healthy human subjects. RESULTS: Respiratory phases determined
      from the BA matched closely to those determined from the RPM: mean (+/- SD)
      difference in phase: -3.9% (+/- 6.4%); mean (+/- SD) absolute difference in
      phase: 10.40% (+/- 3.3%); mean (+/- SD) correlation coefficient: 0.93 (+/- 0.04).
      In the motion phantom study, 4D-MRI clearly showed the sinusoidal motion of the
      phantom; image artifacts observed were minimal to none. Motion trajectories
      measured from 4D-MRI and 2D cine-MRI (used as a reference) matched excellently:
      the mean (+/- SD) absolute difference in motion amplitude: -0.3 (+/- 0.5) mm. In
      the 4D-XCAT phantom study, the simulated "4D-MRI" images showed good consistency
      with the original 4D-XCAT phantom images. The motion trajectory of the
      hypothesized "tumor" matched excellently between the two, with a mean (+/- SD)
      absolute difference in motion amplitude of 0.5 (+/- 0.4) mm. 4D-MRI was able to
      reveal the respiratory motion of internal organs in both human subjects; superior
      inferior (SI) maximum motion of the left kidney of Subject #1 and the diaphragm
      of Subject #2 measured from 4D-MRI was 0.88 and 1.32 cm, respectively.
      CONCLUSIONS: Preliminary results of our study demonstrated the feasibility of a
      novel retrospective 4D-MRI technique that uses body area as a respiratory
      surrogate.

PMID- 22149824
TI  - Bypassing absorbing objects in focused ultrasound using computer generated
      holographic technique.
AB  - PURPOSE: Focused ultrasound (FUS) technology is based on heating a small volume
      of tissue, while keeping the temperature outside the focus region with minimal
      heating only. Several FUS applications, such as brain and liver, suffer from the
      existence of ultrasound absorbers in the acoustic path between the transducer and
      the focus. These absorbers are a potential risk for the FUS therapy since they
      might cause to unwanted heating outside the focus region. An acoustic simulation
      based solution for reducing absorbers' heating is proposed, demonstrated, and
      compared to the standard geometrical solution. The proposed solution uses 3D
      continuous acoustic holograms, generated by the Gerchberg-Saxton (GS) algorithm,
      which are described and demonstrated for the first time using ultrasound planar
      phased-array transducer. METHODS: Holograms were generated using the iterative GS
      algorithm and fast Fourier transform (FFT) acoustic simulation. The performances
      of the holograms are demonstrated by temperature elevation images of the
      absorber, acquired by GE 1.5T MRI scanner equipped with InSightec FUS planar
      phased-array transducer built out of 986 transmitting elements. RESULTS: The
      acoustic holographic technology is demonstrated numerically and experimentally
      using the three letters patterns, "T," "A," and "U," which were manually built
      into 1 * 1 cm masks to represent the requested target fields. 3D holograms of a
      focused ultrasound field with a hole in intensity at the absorber region were
      generated and compared to the standard geometrical solution. The proposed
      holographic solution results in 76% reduction of heating on absorber, while
      keeping similar heating at the focus. CONCLUSIONS: In the present work we show
      for the first time the generation of efficient and uniform continuous ultrasound
      holograms in 3D. We use the holographic technology to generate a FUS beams that
      bypasses an absorber in the acoustic path to reduce unnecessary heating and
      potential clinical risk. The developed technique is superior in performance and
      flexibility compared to the intuitive geometrical technique that is being used in
      clinical practice.

PMID- 22149825
TI  - A comparative study of a dual-energy-like imaging technique based on counting
      integrating readout.
AB  - PURPOSE: The recent introduction of a specific electronic readout chip, designed
      for the processing of the same signal pulses from an x-ray sensor in one
      integrating and one counting channel in each pixel E. Kraft et al., [IEEE Trans.
      Nucl. Sci. 54, 383-390 (2007)]; E. Kraft, "Counting and integrating
      microelectronics development for direct conversion X-ray imaging," Ph.D. thesis,
      2007; J. Fink, "Characterization of the imaging performance of the simultaneously
      counting and integrating X-ray detector CIX," Ph.D. thesis, 2010, enables an
      alternative to conventional dual-energy imaging methods. As shown in a previous
      paper, the proposed alternative benefits from positively correlated noise in the
      raw data, inherent to the counting-integrating readout (CIX), which results in a
      reduction of basis image noise after dual-energy decomposition. In the present
      paper, the authors compare the new approach to dual-energy imaging to two
      conventional dual-energy techniques, the dual-kV technique and the dual-crystal
      technique and to a photon-counting technique based on two energy windows.
      METHODS: The study is based on x-ray computed tomography (CT) simulations of an
      anthropomorphic head phantom, where the signal-to-noise ratios and the contrast
      to-noise ratios in basis material images and quasi-monochromatic images at 60 keV
      are compared. Moreover, a simple pictorial illustration of the relevance of input
      noise correlations in the noise-propagation process during the dual-energy basis
      material decomposition are presented, as well as measurement data for the
      correlation obtained as a function of the x-ray flux rate. RESULTS: Under the
      idealized assumptions of the absence of scatter and detector imperfections like K
      escape, crosstalk and detector noise, our comparison shows that among the dual
      energy techniques investigated, the CIX concept together with the dual-kV
      technique performs best, confirming the mitigating effect of correlated
      measurement data on the dual-energy basis material decomposition. CONCLUSIONS:
      The novel concept of simultaneous counting of photons and integrating the x-ray
      energy flux has a large potential for dual-energy applications in both projection
      and tomographic x-ray imaging. Future work will have to focus on the sensitivity
      of the CIX dual-energy concept to scattered radiation, detector imperfections and
      high x-ray fluxes.

PMID- 22149826
TI  - High resolution dual detector volume-of-interest cone beam breast CT-
      Demonstration with a bench top system.
AB  - PURPOSE: In this study, we used a small field high resolution detector in
      conjunction with a full field flat panel detector to implement and investigate
      the dual detector volume-of-interest (VOI) cone beam breast computed tomography
      (CBCT) technique on a bench-top system. The potential of using this technique to
      image small calcifications without increasing the overall dose to the breast was
      demonstrated. Significant reduction of scatter components in the high resolution
      projection image data of the VOI was also shown. METHODS: With the regular flat
      panel based CBCT technique, exposures were made at 80 kVp to generate an air
      kerma of 6 mGys at the isocenter. With the dual detector VOI CBCT technique, a
      high resolution small field CMOS detector was used to scan a cylindrical VOI (2.5
      cm in diameter and height, 4.5 cm off-center) with collimated x-rays at four
      times of regular exposure level. A flat panel detector was used for full field
      scan with low x-ray exposures at half of the regular exposure level. The low
      exposure full field image data were used to fill in the truncated space in the
      VOI scan data and generate a complete projection image set. The Feldkamp-Davis
      Kress (FDK) filtered backprojection algorithm was used to reconstruct high
      resolution images for the VOI. Two scanning techniques, one breast centered and
      the other VOI centered, were implemented and investigated. Paraffin cylinders
      with embedded thin aluminum (Al) wires were imaged and used in conjunction with
      optically stimulated luminescence (OSL) dose measurements to demonstrate the
      ability of this technique to image small calcifications without increasing the
      mean glandular dose (MGD). RESULTS: Using exposures that produce an air kerma of
      6 mGys at the isocenter, the regular CBCT technique was able to resolve the cross
      sections of Al wires as thin as 254 MUm in diameter in the phantom. For the
      specific VOI studied, by increasing the exposure level by a factor of 4 for the
      VOI scan and reducing the exposure level by a factor of 2 for the full filed
      scan, the dual-detector CBCT technique was able to resolve the cross-sections of
      Al wires as thin as 152 MUm in diameter. The CNR evaluated for the entire Al wire
      cross-section was found to be improved from 5.5 in regular CBCT to 14.4 and 16.8
      with the breast centered and VOI centered scanning techniques, respectively. Even
      inside VOI center, the VOI scan resulted in significant dose saving with the dose
      reduced by a factor of 1.6 at the VOI center. Dose saving outside the VOI was
      substantial with the dose reduced by a factor of 7.3 and 7.8 at the breast center
      for the breast centered and VOI centered scans, respectively, when compared to
      full field scan at the same exposure level. The differences between the two dual
      detector techniques in terms of dose saving and scatter reduction were small with
      VOI scan at 4* exposure level and full field scan at 0.5 * exposure level. The
      MGDs were only 94% of that from the regular CBCT scan. CONCLUSIONS: For the
      specific VOI studied, the dual detector VOI CBCT technique has the potential to
      provide high quality images inside the VOI with MGD similar to or even lower than
      that of full field breast CBCT. It was also found that our results were
      compromised by the use of inadequate detectors for the VOI scan. An appropriately
      selected detector would better optimize the image quality improvement that can be
      achieved with the VOI CBCT technique.

PMID- 22149827
TI  - Companding technique for high dynamic range measurements using Gafchromic films.
AB  - PURPOSE: To introduce a methodology to perform dose measurements using Gafchromic
      films which can span several decades of dose levels. METHODS: The technique is
      based on a rescaling approach using different films irradiated at different dose
      levels. This is combined with a registration protocol correcting positioning and
      scaling factors for each film. The methodology is validated using TLD's for out
      of-field doses. Furthermore, two examples are provided using the technique to
      characterize small sized radiosurgery cones and compared with measurements made
      with a pinpoint chamber. RESULTS: Excellent agreement with TLD, planning systems
      and measurement was found. The superior resolution of the film technique was
      apparent. CONCLUSIONS: The authors have introduced a new technique allowing users
      to quantify very low doses in conjunction with commissioning measurements. The
      use of film also provides 2D information on beam characteristics in high
      resolution measurements.

PMID- 22149828
TI  - Predicting the fidelity of JPEG2000 compressed CT images using DICOM header
      information.
AB  - PURPOSE: To propose multiple logistic regression (MLR) and artificial neural
      network (ANN) models constructed using digital imaging and communications in
      medicine (DICOM) header information in predicting the fidelity of Joint
      Photographic Experts Group (JPEG) 2000 compressed abdomen computed tomography
      (CT) images. METHODS: Our institutional review board approved this study and
      waived informed patient consent. Using a JPEG2000 algorithm, 360 abdomen CT
      images were compressed reversibly (n = 48, as negative control) or irreversibly
      (n = 312) to one of different compression ratios (CRs) ranging from 4:1 to 10:1.
      Five radiologists independently determined whether the original and compressed
      images were distinguishable or indistinguishable. The 312 irreversibly compressed
      images were divided randomly into training (n = 156) and testing (n = 156) sets.
      The MLR and ANN models were constructed regarding the DICOM header information as
      independent variables and the pooled radiologists' responses as dependent
      variable. As independent variables, we selected the CR (DICOM tag number: 0028,
      2112), effective tube current-time product (0018, 9332), section thickness (0018,
      0050), and field of view (0018, 0090) among the DICOM tags. Using the training
      set, an optimal subset of independent variables was determined by backward
      stepwise selection in a four-fold cross-validation scheme. The MLR and ANN models
      were constructed with the determined independent variables using the training
      set. The models were then evaluated on the testing set by using receiver
      operating-characteristic (ROC) analysis regarding the radiologists' pooled
      responses as the reference standard and by measuring Spearman rank correlation
      between the model prediction and the number of radiologists who rated the two
      images as distinguishable. RESULTS: The CR and section thickness were determined
      as the optimal independent variables. The areas under the ROC curve for the MLR
      and ANN predictions were 0.91 (95% CI; 0.86, 0.95) and 0.92 (0.87, 0.96),
      respectively. The correlation coefficients of the MLR and ANN predictions with
      the number of radiologists who responded as distinguishable were 0.76 (0.69,
      0.82, p < 0.001) and 0.78 (0.71, 0.83, p < 0.001), respectively. CONCLUSIONS: The
      MLR and ANN models constructed using the DICOM header information offer promise
      in predicting the fidelity of JPEG2000 compressed abdomen CT images.

PMID- 22149829
TI  - Improving superficial target delineation in radiation therapy with endoscopic
      tracking and registration.
AB  - PURPOSE: Target delineation within volumetric imaging is a critical step in the
      planning process of intensity modulated radiation therapy. In endoluminal
      cancers, endoscopy often reveals superficial areas of visible disease beyond what
      is seen on volumetric imaging. Quantitatively relating these findings to the
      volumetric imaging is prone to human error during the recall and contouring of
      the target. We have developed a method to improve target delineation in the
      radiation therapy planning process by quantitatively registering endoscopic
      findings contours traced on endoscopic images to volumetric imaging. METHODS:
      Using electromagnetic sensors embedded in an endoscope, 2D endoscopic images were
      registered to computed tomography (CT) volumetric images by tracking the position
      and orientation of the endoscope relative to a CT image set. Regions-of-interest
      (ROI) in the 2D endoscopic view were delineated. A mesh created within the
      boundary of the ROI was projected onto the 3D image data, registering the ROI
      with the volumetric image. This 3D ROI was exported to clinical radiation
      treatment planning software. The precision and accuracy of the procedure was
      tested on two solid phantoms with superficial markings visible on both endoscopy
      and CT images. The first phantom was T-shaped tube with X-marks etched on the
      interior. The second phantom was an anatomically correct skull phantom with a
      phantom superficial lesion placed on the pharyngeal surface. Markings were
      contoured on the endoscope images and compared with contours delineated in the
      treatment planning system based on the CT images. Clinical feasibility was tested
      on three patients with early stage glottic cancer. Image-based rendering using
      manually identified landmarks was used to improve the registration. RESULTS:
      Using the T-shaped phantom with X-markings, the 2D to 3D registration accuracy
      was 1.5-3.5 mm, depending on the endoscope position relative to the markings.
      Intraobserver standard variation was 0.5 mm. Rotational accuracy was within 2
      degrees . Using the skull phantom, registration accuracy was assessed by
      calculating the average surface minimum distance between the endoscopy and
      treatment planning contours. The average surface distance was 0.92 mm with 93% of
      all points in the 2D-endoscopy ROI within 1.5 mm of any point within the ROI
      contoured in the treatment planning software. This accuracy is limited by the CT
      imaging resolution and the electromagnetic (EM) sensor accuracy. The clinical
      testing demonstrated that endoscopic contouring is feasible. With registration
      based on em tracking only, accuracy was 5.6-8.4 mm. Image-based registration
      reduced this error to less than 3.5 mm and enabled endoscopic contouring in all
      cases. CONCLUSIONS: Registration of contours generated on 2D endoscopic images to
      3D planning space is feasible, with accuracy smaller than typical set-up margins.
      Used in addition to standard 3D contouring methods in radiation planning, the
      technology may improve gross tumour volume (GTV) delineation for superficial
      tumors in luminal sites that are only visible in endoscopy.

PMID- 22149830
TI  - Potential of high-Z contrast agents in clinical contrast-enhanced computed
      tomography.
AB  - PURPOSE: Currently, only iodine- and barium-based contrast media (CM) are used in
      clinical contrast-enhanced computed tomography (CE-CT). High-Z metals would
      produce a higher contrast at equal mass density for the x-ray spectra used in
      clinical CT. Using such materials might allow for significant dose reductions in
      CE-CT. The purpose of this study was to quantify the potential for dose reduction
      when using CM based on heavy metals. METHODS: The contrast-to-noise ratio
      weighted by dose (CNRD) was determined as a function of scan protocol by means of
      measurements and simulations on a clinical CT scanner. For simulations, water
      cylinders with diameters 160, 320, 480, and 640 mm were used to cover a broad
      range of patient sizes. Measurements were conducted with 160 and 320 mm water
      equivalent plastic cylinders. A central bore of 13 mm diameter was present in all
      phantoms. The tube voltage was varied from 80 to 140 kV for measurements and from
      60 to 180 kV for simulations. Additional tin filtration of thicknesses 0.4, 0.8,
      and 1.2 mm was applied in the simulation to evaluate a range of spectral
      hardness. The bore was filled with a mixture of water and 10 mg/ml of pure
      iodine, holmium, gadolinium, ytterbium, osmium, tungsten, gold, and bismuth for
      the simulations and with aqueous solutions of ytterbium, tungsten, gold, and
      bismuth salts as well as Iopromid containing 10 mg/ml of the pure materials for
      the measurements. CNRDs were compared to iodine at phantom size-dependent
      reference voltages for all high-Z materials and the resulting dose reduction was
      calculated for equal contrast-to-noise ratio. RESULTS: Dose reduction potentials
      strongly depended on phantom size, spectral hardness, and tube voltage. Depending
      on the added filtration, a dose reduction of 19%-60% could be reached at 80 kV
      with gadolinium for the 160 mm phantom, 52%-69% at 100 kV with holmium for the
      320 mm phantom, 62%-78% with 120 kV for hafnium and the 480 mm phantom and 74%
      86% with 140 kV for gold and the 640 mm phantom. While gadolinium might be
      considered at 160 mm diameter, hafnium showed the best overall performance for
      phantom sizes of 320 mm and above. The measurements conducted on the clinical CT
      scanner showed very good agreement with simulations with deviations in the order
      of 5 to 10%. CONCLUSIONS: The results of this study encourage the development and
      use of CM based on high-Z materials, especially for adipose patients, where high
      tube voltages are necessary to reach sufficiently short scan times. Hafnium
      proved to be the best compromise for average-size and for adipose patients. Even
      higher-Z materials such as gold and bismuth showed a good overall performance in
      conjunction with high tube voltage, large patients or strong added filtration and
      may be recommended for scans under these conditions.

PMID- 22149831
TI  - Spatial correlation of proton irradiation-induced activity and dose in polymer
      gel phantoms for PET/CT delivery verification studies.
AB  - PURPOSE: This work demonstrates a novel application of BANG3-Pro2 polymer gel
      dosimeter as a dosimetric phantom able to accurately capture both dose and
      induced activity. METHODS: BANG3-Pro2 dosimeters were irradiated with a clinical
      proton beam using an unmodulated beam and a spread-out Bragg peak (SOBP)
      modulation, the latter with a Lucite compensator to introduce a range offset in
      one quadrant of the circular field. The dosimeters were imaged in a nearby
      positron emission tomography/computed tomography (PET/CT) unit starting within 5
      min of beam-off. Induced positron emission (PE) activity along the central axis
      of the beam was compared to analytical calculations. Dose distributions were read
      out using an optical CT scanner and were validated against ion chamber
      measurements and the treatment plan. The offset between the distal fall-off of
      dose and activity (50% level) was determined over the entire irradiated field.
      Lateral profiles of PE were correlated to measured dose for the unmodulated beam
      delivery. RESULTS: Measured profiles of PE activity along the central beam axis
      were found to be within 10% of the predictions of analytical calculations. The
      depth-dose profiles agreed with the reference values (ion chamber or treatment
      plan) within 3%. The offset between the depth profiles of dose and activity for
      the unmodulated beam was 8.4 +/- 1.4 mm. For the compensator-based SOBP delivery,
      the distribution of offsets throughout the field was found to be bimodal, with
      the mean of 8.9 +/- 2.8 mm for the thinner region of the compensator and 4.3 +/-
      2.5 mm for the thicker region. For the pristine beam delivery, lateral profiles
      of dose and activity were found to exhibit fair spatial correlation throughout
      the beam range, with the mean 2D gamma index of 0.42 and 91% of the evaluated
      pixels passing the test. CONCLUSIONS: This work presents the first demonstration
      of simultaneous and accurate experimental measurement of three-dimensional
      distributions of dose and induced activity and lays the groundwork for further
      investigations using BANG3-Pro2 as a dosimetric phantom in PET/CT delivery
      verification studies.

PMID- 22149832
TI  - Effects of exposure equalization on image signal-to-noise ratios in digital
      mammography: a simulation study with an anthropomorphic breast phantom.
AB  - PURPOSE: The scan equalization digital mammography (SEDM) technique combines slot
      scanning and exposure equalization to improve low-contrast performance of digital
      mammography in dense tissue areas. In this study, full-field digital mammography
      (FFDM) images of an anthropomorphic breast phantom acquired with an anti-scatter
      grid at various exposure levels were superimposed to simulate SEDM images and
      investigate the improvement of low-contrast performance as quantified by primary
      signal-to-noise ratios (PSNRs). METHODS: We imaged an anthropomorphic breast
      phantom (Gammex 169 "Rachel," Gammex RMI, Middleton, WI) at various exposure
      levels using a FFDM system (Senographe 2000D, GE Medical Systems, Milwaukee, WI).
      The exposure equalization factors were computed based on a standard FFDM image
      acquired in the automatic exposure control (AEC) mode. The equalized image was
      simulated and constructed by superimposing a selected set of FFDM images acquired
      at 2, 1, 1/2, 1/4, 1/8, 1/16, and 1/32 times of exposure levels to the standard
      AEC timed technique (125 mAs) using the equalization factors computed for each
      region. Finally, the equalized image was renormalized regionally with the
      exposure equalization factors to result in an appearance similar to that with
      standard digital mammography. Two sets of FFDM images were acquired to allow for
      two identically, but independently, formed equalized images to be subtracted from
      each other to estimate the noise levels. Similarly, two identically but
      independently acquired standard FFDM images were subtracted to estimate the noise
      levels. Corrections were applied to remove the excess system noise accumulated
      during image superimposition in forming the equalized image. PSNRs over the
      compressed area of breast phantom were computed and used to quantitatively study
      the effects of exposure equalization on low-contrast performance in digital
      mammography. RESULTS: We found that the highest achievable PSNR improvement
      factor was 1.89 for the anthropomorphic breast phantom used in this study. The
      overall PSNRs were measured to be 79.6 for the FFDM imaging and 107.6 for the
      simulated SEDM imaging on average in the compressed area of breast phantom,
      resulting in an average improvement of PSNR by ~35% with exposure equalization.
      We also found that the PSNRs appeared to be largely uniform with exposure
      equalization, and the standard deviations of PSNRs were estimated to be 10.3 and
      7.9 for the FFDM imaging and the simulated SEDM imaging, respectively. The
      average glandular dose for SEDM was estimated to be 212.5 mrad, ~34% lower than
      that of standard AEC-timed FFDM (323.8 mrad) as a result of exposure equalization
      for the entire breast phantom. CONCLUSIONS: Exposure equalization was found to
      substantially improve image PSNRs in dense tissue regions and result in more
      uniform image PSNRs. This improvement may lead to better low-contrast performance
      in detecting and visualizing soft tissue masses and micro-calcifications in dense
      tissue areas for breast imaging tasks.

PMID- 22149833
TI  - Rhodium self-powered neutron detector as a suitable on-line thermal neutron flux
      monitor in BNCT treatments.
AB  - PURPOSE: A rhodium self-powered neutron detector (Rh SPND) has been specifically
      developed by the Comision Nacional de Energia Atomica (CNEA) of Argentina to
      measure locally and in real time thermal neutron fluxes in patients treated with
      boron neutron capture therapy (BNCT). In this work, the thermal and epithermal
      neutron response of the Rh SPND was evaluated by studying the detector response
      to two different reactor spectra. In addition, during clinical trials of the BNCT
      Project of the CNEA, on-line neutron flux measurements using the specially
      designed detector were assessed. METHODS: The first calibration of the detector
      was done with the well-thermalized neutron spectrum of the CNEA RA-3 reactor
      thermal column. For this purpose, the reactor spectrum was approximated by a
      Maxwell-Boltzmann distribution in the thermal energy range. The second
      calibration was done at different positions along the central axis of a water
      filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam
      of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been
      well characterized by both calculation and measurement, and it presented some
      marked differences with the ideal spectrum considered for SPND calibrations at RA
      3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom
      and thus the percentage of the epithermal contribution to the total neutron flux
      changed at each measurement location. Local (one point-position) and global
      (several points-positions) and thermal and mixed-field thermal neutron
      sensitivities were determined from these measurements. Thermal neutron flux was
      also measured during BNCT clinical trials within the irradiation fields incident
      on the patients. In order to achieve this, the detector was placed on patient's
      skin at dosimetric reference points for each one of the fields. System stability
      was adequate for this kind of measurement. RESULTS: Local mixed-field thermal
      neutron sensitivities and global thermal and mixed-field thermal neutron
      sensitivities derived from measurements performed at the RA-6 were compared and
      no significant differences were found. Global RA-6-based thermal neutron
      sensitivity showed agreement with pure thermal neutron sensitivity measurements
      performed in the RA-3 spectrum. Additionally, the detector response proved nearly
      unchanged by differences in neutron spectra from real (RA-6 BNCT beam) and ideal
      (considered for calibration calculations at RA-3) neutron source descriptions.
      The results confirm that the special design of the Rh SPND can be considered as
      having a pure thermal response for neutron spectra with epithermal-to-thermal
      flux ratios up to 12%. In addition, the linear response of the detector to
      thermal flux allows the use of a mixed-field thermal neutron sensitivity of 1.95
      +/- 0.05 * 10(-21) A n(-1)[middle dot]cm2 [middle dot]s. This sensitivity can be
      used in spectra with up to 21% epithermal-to-thermal flux ratio without
      significant error due to epithermal neutron and gamma induced effects. The values
      of the measured fluxes in clinical applications had discrepancies with calculated
      results that were in the range of -25% to +30%, which shows the importance of a
      local on-line independent measurement as part of a treatment planning quality
      control system. CONCLUSIONS: The usefulness of the CNEA Rh SPND for the on-line
      local measurement of thermal neutron flux on BNCT patients has been demonstrated
      based on an appropriate neutron spectra calibration and clinical applications.

PMID- 22149834
TI  - Calculation of k(Q(clin),Q(msr) ) (f(clin),f(msr) ) for several small detectors
      and for two linear accelerators using Monte Carlo simulations.
AB  - PURPOSE: The scope of this study was to determine a complete set of correction
      factors for several detectors in static small photon fields for two linear
      accelerators (linacs) and for several detectors. METHODS: Measurements for Monte
      Carlo (MC) commissioning were performed for two linacs, Siemens Primus and Elekta
      Synergy. After having determined the source parameters that best fit the
      measurements of field specific output factors, profiles, and tissue-phantom
      ratio, the generalized version of the classical beam quality correction factor
      for static small fields, k(Q(clin),Q(msr) ) (f(clin),f(msr) ), were determined
      for several types of detectors by using the egs_chamber Monte Carlo user code
      which can accurately reproduce the geometry and the material composition of the
      detector. The influence of many parameters (energy and radial FWHM of the
      electron beam source, field dimensions, type of accelerator) on the value of
      k(Q(clin),Q(msr) ) (f(clin),f(msr) ) was evaluated. Moreover, a MC analysis of
      the parameters that influence the change of k(Q(clin),Q(msr) ) (f(clin),f(msr) )
      as a function of field dimension was performed. A detailed analysis of
      uncertainties related to the measurements of the field specific output factor and
      to the Monte Carlo calculation of k(Q(clin),Q(msr) ) (f(clin),f(msr) ) was done.
      RESULTS: The simulations demonstrated that the correction factor k(Q(clin),Q(msr)
      ) (f(clin),f(msr) ) can be considered independent from the quality beam factor Q
      in the range 0.68  +/-  0.01 for all the detectors analyzed. The k(Q(clin),Q(msr)
      ) (f(clin),f(msr) ) of PTW 60012 and EDGE diodes can be assumed dependent only on
      the field size, for fields down to 0.5 * 0.5 cm2. The microLion, and the
      microchambers, instead, must be used with some caution because they exhibit a
      slight dependence on the radial FWHM of the electron source, and therefore, a
      correction factor only dependent on field size can be used for fields >= 0.75 *
      0.75 and >= 1.0 * 1.0 cm2, respectively. The analysis of uncertainties gave an
      estimate of uncertainty for the 0.5 * 0.5 cm2 field of about 0.7% (1sigma) for
      k(Q(clin),Q(msr) ) (f(clin),f(msr) ) factor and of about 1.0% (1sigma) for the
      field output factor, Omega(Q(clin),Q(msr) ) (f(clin),f(msr) ), of diodes,
      microchambers, and microLion. CONCLUSIONS: Stereotactic diodes with the
      appropriate k(Q(clin),Q(msr) ) (f(clin),f(msr) ) are recommended for determining
      Omega(Q(clin),Q(msr) ) (f(clin),f(msr) ) of small photon beams.

PMID- 22149835
TI  - A self-adaptive case-based reasoning system for dose planning in prostate cancer
      radiotherapy.
AB  - PURPOSE: Prostate cancer is the most common cancer in the male population.
      Radiotherapy is often used in the treatment for prostate cancer. In radiotherapy
      treatment, the oncologist makes a trade-off between the risk and benefit of the
      radiation, i.e., the task is to deliver a high dose to the prostate cancer cells
      and minimize side effects of the treatment. The aim of our research is to develop
      a software system that will assist the oncologist in planning new treatments.
      METHODS: A nonlinear case-based reasoning system is developed to capture the
      expertise and experience of oncologists in treating previous patients. Importance
      (weights) of different clinical parameters in the dose planning is determined by
      the oncologist based on their past experience, and is highly subjective. The
      weights are usually fixed in the system. In this research, the weights are
      updated automatically each time after generating a treatment plan for a new
      patient using a group based simulated annealing approach. RESULTS: The developed
      approach is analyzed on the real data set collected from the Nottingham
      University Hospitals NHS Trust, City Hospital Campus, UK. Extensive experiments
      show that the dose plan suggested by the proposed method is coherent with the
      dose plan prescribed by an experienced oncologist or even better. CONCLUSIONS:
      The developed case-based reasoning system enables the use of knowledge and
      experience gained by the oncologist in treating new patients. This system may
      play a vital role to assist the oncologist in making a better decision in less
      computational time; it utilizes the success rate of the previously treated
      patients and it can also be used in teaching and training processes.

PMID- 22149836
TI  - A feasibility study of using couch-based real time dosimetric device in external
      beam radiotherapy.
AB  - PURPOSE: Measurement of actual dose delivered during radiotherapy treatment aids
      in checking the accuracy of dose delivered to the patient. In this study, a couch
      based real time dosimetric device has been proposed to measure the exit or
      entrance dose to a patient during external beam radiotherapy. The utility and
      feasibility of such a device using a 2D array of diodes has been demonstrated.
      METHODS: Two MAPCHECK devices: MAPCHECK (1175) and MAPCHECK 2 (both SunNuclear)
      were embedded in a foam block in the treatment couch of a Varian 21iX linear
      accelerator. The angular dependence of the detector response for both devices was
      studied before implementing the MAPCHECKs for experimental purposes. An Alderson
      Rando head phantom was scanned with the MAPCHECK and MAPCHECK 2 devices
      separately and four different treatment plans were generated with target volumes
      at three different positions simulating typical clinical situations. The
      analytical anisotropic algorithm (AAA) was used to compute the doses in an
      Eclipse treatment planning system (Varian Medical Systems). The Rando phantom
      with the MAPCHECK device was exposed in Clinac 21iX linear accelerator. The
      measured dose distribution was compared with the calculated dose distribution to
      check for the accuracy in dose delivery. RESULTS: Measured and computed dose
      distribution were found to agree with more than 93% of pixels passing at 3% and 3
      mm gamma criteria for all the treatment plans. The couch-based real time
      dosimetry system may also be applied for noncoplanar beams where electronic
      portal imaging device (EPID) is not practical to measure the dose. Other
      advantages include checking the beam stability during the patient treatment,
      performing routine morning quality assurance (QA) tests in the linear
      accelerator, and to perform pretreatment verification of intensity modulated
      radiation therapy (IMRT). One of the drawbacks of this system is that it cannot
      be used for measuring the dose at 90 degrees  or 270 degrees  gantry angles.
      CONCLUSIONS: This preliminary study shows that a 2D array of detectors may be
      used as part of the treatment couch for real time patient dosimetry in studying
      the dose delivered to the patient in real time and also for performing routine
      quality assurance.

PMID- 22149837
TI  - Use of radiation protraction to escalate biologically effective dose to the
      treatment target.
AB  - PURPOSE: The aim of this study is to evaluate how simultaneously increasing
      fraction time and dose per fraction affect biologically effective dose for the
      target (BED(tar)) while biologically effective dose for the normal tissue
      (BED(nt)) is fixed. METHODS: In this investigation, BED(tar) and BED(nt) were
      studied by assuming mono-exponential repair of sublethal damage with tissue
      dependent repair half-time. RESULTS: Our results demonstrate that under certain
      conditions simultaneously increasing fraction time and dose per fraction result
      in increased BED(tar) while BED(nt) is fixed. The dependence of biologically
      effective dose on fraction time is influenced by the dose rate. In this
      investigation we analytically determined time-varying dose rate R which minimizes
      BED. Changes in BED with fraction time were compared for constant dose rate and
      for R. CONCLUSIONS: A number of recent experimental and theoretical studies have
      demonstrated that slow delivery of radiation (known as radiation protraction)
      leads to reduced therapeutic effect because of increased repair of sublethal
      damage. In contrast, our analysis shows that under certain conditions
      simultaneously increasing fraction time and dose per fraction are
      radiobiologically advantageous.

PMID- 22149838
TI  - A generic, geometric cocalibration method for a combined system of fluorescence
      molecular tomography and microcomputed tomography with arbitrarily shaped
      objects.
AB  - PURPOSE: A combined system of fluorescence molecular tomography and microcomputed
      tomography (FMT&mCT) can provide molecular and anatomical information of small
      animals in a single study with intrinsically coregistered images. The anatomical
      information provided by the mCT subsystem is commonly used as a reference to
      locate the fluorophore distribution or as a priori structural information to
      improve the performance of FMT. Therefore, the transformation between the
      coordinate systems of the subsystem needs to be determined in advanced. METHODS:
      A cocalibration method for the combined system of FMT&mCT is proposed. First,
      linear models are adopted to describe the galvano mirrors and the charge-coupled
      device (CCD) camera in the FMT subsystem. Second, the position and orientation of
      the galvano mirrors are determined with the input voltages of the galvano mirrors
      and the markers, whose positions are predetermined. The position, orientation and
      normalized pixel size of the CCD camera are obtained by analysing the projections
      of a point-like marker at different positions. Finally, the orientation and
      position of sources and the corresponding relationship between the detectors and
      their projections on the image plane are predicted. Because the positions of the
      markers are acquired with mCT, the registration of the FMT and mCT could be
      realized by direct image fusion. RESULTS: The accuracy and consistency of this
      method in the presence of noise is evaluated by computer simulation. Next, a
      practical implementation for an experimental FMT&mCT system is carried out and
      validated. The maximum prediction error of the source positions on the surface of
      a cylindrical phantom is within 0.375 mm and that of the projections of a point
      like marker is within 0.629 pixel. Finally, imaging experiments of the
      fluorophore distribution in a cylindrical phantom and a phantom with a complex
      shape demonstrate the feasibility of the proposed method. CONCLUSIONS: This
      method is universal in FMT&mCT, which could be performed with no restriction on
      the system geometry, calibration phantoms or imaging objects.

PMID- 22149839
TI  - Effects of motion, attenuation, and scatter corrections on gated cardiac SPECT
      reconstruction.
AB  - PURPOSE: In gated cardiac single photon emission computed tomography (SPECT),
      image reconstruction is often hampered by various degrading factors including
      depth-dependent spatial blurring, attenuation, scatter, motion blurring, and low
      data counts. Consequently, there has been significant development in image
      reconstruction methods for improving the quality of reconstructed images. The
      goal of this work is to investigate how these degrading factors will impact the
      reconstructed myocardium when different reconstruction methods are used. METHODS:
      The authors conduct a comparative study of the effects of these degrading factors
      on the accuracy of myocardium by several reconstruction algorithms, including (1)
      a clinical spatiotemporal processing method, (2) maximum likelihood (ML)
      estimation, (3) 3D maximum a posteriori (MAP) estimation, (4) 3D MAP with
      posttemporal filtering, and (5) motion-compensated spatiotemporal (4D)
      reconstruction. To quantify the reconstruction results, the authors use the
      following measures on different aspects of the myocardium: (1) overall error
      level in the myocardium, (2) regional accuracy of the left ventricle (LV) wall,
      (3) uniformity of the LV, (4) accuracy of regional time activity curves by
      normalized cross-correlation coefficient, and (5) perfusion defect detectability.
      The authors also assess the effectiveness of degrading corrections in
      reconstruction by considering an upper bound for each reconstruction method,
      which represents what would be achieved by each method if the acquired data were
      free from attenuation and scatter degradations. In the experiments the authors
      use Monte Carlo simulated cardiac gated SPECT imaging based on the 4D NURBS-based
      cardiac-torso (NCAT) phantom with different patient geometry and lesion settings,
      in which the simulated ground truth is known for the purpose of quantitative
      evaluation. RESULTS: The results demonstrate that use of temporal processing in
      reconstruction (Methods 1, 4, and 5 above) can greatly improve the reconstructed
      myocardium in terms of both error level and perfusion defect detection. In low
      count gated studies, it can have even greater impact than other degrading
      factors. Both attenuation and scatter corrections can lead to reduced error
      levels in the myocardium in all methods; in particular, with 4D the bias can be
      reduced by as much as four-fold compared to no correction. There is a slight
      increase in noise level observed with scatter correction. A significant
      improvement in heart wall appearance is demonstrated in reconstruction results
      from three sets of clinical acquisitions as correction for degradations is
      combined with refinement of temporal filtering. CONCLUSIONS: Correction for
      degrading factors such as resolution, attenuation, scatter, and motion blur can
      all lead to improved image quality in cardiac gated SPECT reconstruction.
      However, their effectiveness could also vary with the reconstruction algorithms
      used. Both attenuation and scatter corrections can effectively reduce the bias
      level of the reconstructed LV wall, though scatter correction is also observed to
      increase the variance level. Use of temporal processing in reconstruction can
      have greater impact on the accuracy of the myocardium than correction of other
      degrading factors. Overall, use of degrading corrections in 4D reconstruction is
      shown to be most effective for improving both reconstruction accuracy of the
      myocardium and detectability of perfusion defects in gated images.

PMID- 22149840
TI  - Dose and dose averaged LET comparison of 1H, 4He, 6Li, 8Be, 10B, 12C, 14N, and
      16O ion beams forming a spread-out Bragg peak.
AB  - PURPOSE: Modern clinical accelerators are capable of producing ion beams from
      protons up to neon. This work compares the depth dose distribution and
      corresponding dose averaged linear energy transfer (LET) distribution, which is
      related to the biological effectiveness, for different ion beams (1H, 4He, 6Li,
      8Be, 10B, 12C, 14N, and 16O) using multi-energetic spectra in order to configure
      spread-out Bragg peaks (SOBP). METHODS: Monte Carlo simulations were performed in
      order to configure a 5 cm SOBP at 8 cm depth in water for all the different ion
      beams. Physical dose and dose averaged LET distributions as a function of depth
      were then calculated and compared. The superposition of dose distribution of all
      ions is also presented for a two opposing fields configuration. Additional
      simulations were performed for (12)C beams to investigate the dependence of dose
      and dose averaged LET distributions on target depth and size, as well as beam
      configuration. These included simulations for a 3 cm SOBP at 7, 10, and 13 cm
      depth in water, a 6 cm SOBP at 7 depth in water, and two opposing fields of 6 cm
      SOBP. RESULTS: Alpha particles and protons present superior physical depth dose
      distributions relative to the rest of the beams studied. Dose averaged LET
      distributions results suggest higher biological effectiveness in the target
      volume for carbon, nitrogen and oxygen ions. This is coupled, however, with
      relatively high LET values-especially for the last two ion species-outside the
      SOBP where healthy tissue would be located. Dose averaged LET distributions for
      8Be and 10B beams show that they could be attractive alternatives to 12C for the
      treatment of small, not deeply seated lesions. The potential therapeutic effect
      of different ion beams studied in this work depends on target volume and
      position, as well as the number of beams used. CONCLUSIONS: The optimization of
      beam modality for specific tumor cites remains an open question that warrants
      further investigation and clinically relevant results.

PMID- 22149841
TI  - Implementing a newly proposed Monte Carlo based small field dosimetry formalism
      for a comprehensive set of diode detectors.
AB  - PURPOSE: The goal of this work was to implement a recently proposed small field
      dosimetry formalism [Alfonso et al., Med. Phys. 35(12), 5179-5186 (2008)] for a
      comprehensive set of diode detectors and provide the required Monte Carlo
      generated factors to correct measurement. METHODS: Jaw collimated square small
      field sizes of side 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, and 3.0 cm normalized to a
      reference field of 5.0 cm * 5.0 cm were used throughout this study. Initial linac
      modeling was performed with electron source parameters at 6.0, 6.1, and 6.2 MeV
      with the Gaussian FWHM decreased in steps of 0.010 cm from 0.150 to 0.100 cm.
      DOSRZnrc was used to develop models of the IBA stereotactic field diode (SFD) as
      well as the PTW T60008, T60012, T60016, and T60017 field diodes. Simulations were
      run and isocentric, detector specific, output ratios (OR(det)) calculated at
      depths of 1.5, 5.0, and 10.0 cm. This was performed using the following source
      parameter subset: 6.1 and 6.2 MeV with a FWHM = 0.100, 0.110, and 0.120 cm. The
      source parameters were finalized by comparing experimental detector specific
      output ratios with simulation. Simulations were then run with the active volume
      and surrounding materials set to water and the replacement correction factors
      calculated according to the newly proposed formalism. RESULTS: In all cases, the
      experimental field size widths (at the 50% level) were found to be smaller than
      the nominal, and therefore, the simulated field sizes were adjusted accordingly.
      At a FWHM = 0.150 cm simulation produced penumbral widths that were too broad.
      The fit improved as the FWHM was decreased, yet for all but the smallest field
      size worsened again at a FWHM = 0.100 cm. The simulated OR(det) were found to be
      greater than, equivalent to and less than experiment for spot size FWHM = 0.100,
      0.110, and 0.120 cm, respectively. This is due to the change in source occlusion
      as a function of FWHM and field size. The corrections required for the 0.5 cm
      field size were 0.95 (+/- 1.0%) for the SFD, T60012 and T60017 diodes and 0.90
      (+/- 1.0%) for the T60008 and T60016 diodes-indicating measured output ratios to
      be 5% and 10% high, respectively. Our results also revealed the correction
      factors to be the same within statistical variation at all depths considered.
      CONCLUSIONS: A number of general conclusions are evident: (1) small field OR(det)
      are very sensitive to the simulated source parameters, and therefore, rigorous
      Monte Carlo linac model commissioning, with respect to measurement, must be
      pursued prior to use, (2) backscattered dose to the monitor chamber should be
      included in simulated OR(det) calculations, (3) the corrections required for
      diode detectors are design dependent and therefore detailed detector modeling is
      required, and (4) the reported detector specific correction factors may be
      applied to experimental small field OR(det) consistent with those presented here.

PMID- 22149842
TI  - Ultrafast and scalable cone-beam CT reconstruction using MapReduce in a cloud
      computing environment.
AB  - PURPOSE: Four-dimensional CT (4DCT) and cone beam CT (CBCT) are widely used in
      radiation therapy for accurate tumor target definition and localization. However,
      high-resolution and dynamic image reconstruction is computationally demanding
      because of the large amount of data processed. Efficient use of these imaging
      techniques in the clinic requires high-performance computing. The purpose of this
      work is to develop a novel ultrafast, scalable and reliable image reconstruction
      technique for 4D CBCT/CT using a parallel computing framework called MapReduce.
      We show the utility of MapReduce for solving large-scale medical physics problems
      in a cloud computing environment. METHODS: In this work, we accelerated the
      Feldcamp-Davis-Kress (FDK) algorithm by porting it to Hadoop, an open-source
      MapReduce implementation. Gated phases from a 4DCT scans were reconstructed
      independently. Following the MapReduce formalism, Map functions were used to
      filter and backproject subsets of projections, and Reduce function to aggregate
      those partial backprojection into the whole volume. MapReduce automatically
      parallelized the reconstruction process on a large cluster of computer nodes. As
      a validation, reconstruction of a digital phantom and an acquired CatPhan 600
      phantom was performed on a commercial cloud computing environment using the
      proposed 4D CBCT/CT reconstruction algorithm. RESULTS: Speedup of reconstruction
      time is found to be roughly linear with the number of nodes employed. For
      instance, greater than 10 times speedup was achieved using 200 nodes for all
      cases, compared to the same code executed on a single machine. Without modifying
      the code, faster reconstruction is readily achievable by allocating more nodes in
      the cloud computing environment. Root mean square error between the images
      obtained using MapReduce and a single-threaded reference implementation was on
      the order of 10(-7). Our study also proved that cloud computing with MapReduce is
      fault tolerant: the reconstruction completed successfully with identical results
      even when half of the nodes were manually terminated in the middle of the
      process. CONCLUSIONS: An ultrafast, reliable and scalable 4D CBCT/CT
      reconstruction method was developed using the MapReduce framework. Unlike other
      parallel computing approaches, the parallelization and speedup required little
      modification of the original reconstruction code. MapReduce provides an efficient
      and fault tolerant means of solving large-scale computing problems in a cloud
      computing environment.

PMID- 22149843
TI  - Potential of discrete Gaussian edge feathering method for improving abutment
      dosimetry in eMLC-delivered segmented-field electron conformal therapy.
AB  - PURPOSE: The purpose of this work was to investigate the potential of discrete
      Gaussian edge feathering of the higher energy electron fields for improving
      abutment dosimetry in the planning volume when using an electron multileaf
      collimator (eMLC) to deliver segmented-field electron conformal therapy (ECT).
      METHODS: A discrete (five-step) Gaussian edge spread function was used to match
      dose penumbras of differing beam energies (6-20 MeV) at a specified depth in a
      water phantom. Software was developed to define the leaf eMLC positions of an
      eMLC that most closely fit each electron field shape. The effect of 1D edge
      feathering of the higher energy field on dose homogeneity was computed and
      measured for segmented-field ECT treatment plans for three 2D PTVs in a water
      phantom, i.e., depth from the water surface to the distal PTV surface varied as a
      function of the x-axis (parallel to leaf motion) and remained constant along the
      y-axis (perpendicular to leaf motion). Additionally, the effect of 2D edge
      feathering was computed and measured for one radially symmetric, 3D PTV in a
      water phantom, i.e., depth from the water surface to the distal PTV surface
      varied as a function of both axes. For the 3D PTV, the feathering scheme was
      evaluated for 0.1-1.0-cm leaf widths. Dose calculations were performed using the
      pencil beam dose algorithm in the Pinnacle(3) treatment planning system. Dose
      verification measurements were made using a prototype eMLC (1-cm leaf width).
      RESULTS: 1D discrete Gaussian edge feathering reduced the standard deviation of
      dose in the 2D PTVs by 34, 34, and 39%. In the 3D PTV, the broad leaf width (1
      cm) of the eMLC hindered the 2D application of the feathering solution to the 3D
      PTV, and the standard deviation of dose increased by 10%. However, 2D discrete
      Gaussian edge feathering with simulated eMLC leaf widths of 0.1-0.5 cm reduced
      the standard deviation of dose in the 3D PTV by 33-28%, respectively.
      CONCLUSIONS: A five-step discrete Gaussian edge spread function applied in 2D
      improves the abutment dosimetry but requires an eMLC leaf resolution better than
      1 cm.

PMID- 22149844
TI  - Modeling of radio-frequency induced currents on lead wires during MR imaging
      using a modified transmission line method.
AB  - PURPOSE: Metallic implants may cause serious tissue heating during magnetic
      resonance (MR) imaging. This heating occurs due to the induced currents caused by
      the radio-frequency (RF) field. Much work has been done to date to understand the
      relationship between the RF field and the induced currents. Most of these
      studies, however, were based purely on experimental or numerical methods. This
      study has three main purposes: (1) to define the RF heating properties of an
      implant lead using two parameters; (2) to develop an analytical formulation that
      directly explains the relationship between RF fields and induced currents; and
      (3) to form a basis for analysis of complex cases. METHODS: In this study, a
      lumped element model of the transmission line was modified to model leads of
      implants inside the body. Using this model, leads are defined using two
      parameters: impedance per unit length, Z, and effective wavenumber along the
      lead, k(t). These two parameters were obtained by using methods that are similar
      to the transmission line theory. As long as these parameters are known for a
      lead, currents induced in the lead can be obtained no matter how complex the lead
      geometry is. The currents induced in bare wire, lossy wire, and insulated wire
      were calculated using this new method which is called the modified transmission
      line method or MoTLiM. First, the calculated induced currents under uniform
      electric field distribution were solved and compared with method-of-moments (MoM)
      calculations. In addition, MoTLiM results were compared with those of phantom
      experiments. For experimental verification, the flip angle distortion due to the
      induced currents was used. The flip angle distribution around a wire was both
      measured by using flip angle imaging methods and calculated using current
      distribution obtained from the MoTLiM. Finally, these results were compared and
      an error analysis was carried out. RESULTS: Bare perfect electric, bare lossy,
      and insulated perfect electric conductor wires under uniform and linearly varying
      electric field exposure were solved, both for 1.5 T and 3 T scanners, using both
      the MoTLiM and MoM. The results are in agreement within 10% mean-square error.
      The flip angle distribution that was obtained from experiments was compared along
      the azimuthal paths with different distances from the wire. The highest mean
      square error was 20% among compared cases. CONCLUSIONS: A novel method was
      developed to define the RF heating properties of implant leads with two
      parameters and analyze the induced currents on implant leads that are exposed to
      electromagnetic fields in a lossy medium during a magnetic resonance imaging
      (MRI) scan. Some simple cases are examined to explain the MoTLiM and a basis is
      formed for the analysis of complex cases. The method presented shows the direct
      relationship between the incident RF field and the induced currents. In addition,
      the MoTLiM reveals the RF heating properties of the implant leads in terms of the
      physical features of the lead and electrical properties of the medium.

PMID- 22149845
TI  - Automated image-based colon cleansing for laxative-free CT colonography computer
      aided polyp detection.
AB  - PURPOSE: To evaluate the performance of a computer-aided detection (CAD) system
      for detecting colonic polyps at noncathartic computed tomography colonography
      (CTC) in conjunction with an automated image-based colon cleansing algorithm.
      METHODS: An automated colon cleansing algorithm was designed to detect and
      subtract tagged-stool, accounting for heterogeneity and poor tagging, to be used
      in conjunction with a colon CAD system. The method is locally adaptive and
      combines intensity, shape, and texture analysis with probabilistic optimization.
      CTC data from cathartic-free bowel preparation were acquired for testing and
      training the parameters. Patients underwent various colonic preparations with
      barium or Gastroview in divided doses over 48 h before scanning. No laxatives
      were administered and no dietary modifications were required. Cases were selected
      from a polyp-enriched cohort and included scans in which at least 90% of the
      solid stool was visually estimated to be tagged and each colonic segment was
      distended in either the prone or supine view. The CAD system was run
      comparatively with and without the stool subtraction algorithm. RESULTS: The
      dataset comprised 38 CTC scans from prone and/or supine scans of 19 patients
      containing 44 polyps larger than 10 mm (22 unique polyps, if matched between
      prone and supine scans). The results are robust on fine details around folds,
      thin-stool linings on the colonic wall, near polyps and in large fluid/stool
      pools. The sensitivity of the CAD system is 70.5% per polyp at a rate of 5.75
      false positives/scan without using the stool subtraction module. This detection
      improved significantly (p = 0.009) after automated colon cleansing on cathartic
      free data to 86.4% true positive rate at 5.75 false positives/scan. CONCLUSIONS:
      An automated image-based colon cleansing algorithm designed to overcome the
      challenges of the noncathartic colon significantly improves the sensitivity of
      colon CAD by approximately 15%.

PMID- 22149846
TI  - A software-based x-ray scatter correction method for breast tomosynthesis.
AB  - PURPOSE: To develop a software-based scatter correction method for digital breast
      tomosynthesis (DBT) imaging and investigate its impact on the image quality of
      tomosynthesis reconstructions of both phantoms and patients. METHODS: A Monte
      Carlo (MC) simulation of x-ray scatter, with geometry matching that of the cranio
      caudal (CC) view of a DBT clinical prototype, was developed using the Geant4
      toolkit and used to generate maps of the scatter-to-primary ratio (SPR) of a
      number of homogeneous standard-shaped breasts of varying sizes. Dimension-matched
      SPR maps were then deformed and registered to DBT acquisition projections,
      allowing for the estimation of the primary x-ray signal acquired by the imaging
      system. Noise filtering of the estimated projections was then performed to reduce
      the impact of the quantum noise of the x-ray scatter. Three dimensional (3D)
      reconstruction was then performed using the maximum likelihood-expectation
      maximization (MLEM) method. This process was tested on acquisitions of a
      heterogeneous 50/50 adipose/glandular tomosynthesis phantom with embedded masses,
      fibers, and microcalcifications and on acquisitions of patients. The image
      quality of the reconstructions of the scatter-corrected and uncorrected
      projections was analyzed by studying the signal-difference-to-noise ratio (SDNR),
      the integral of the signal in each mass lesion (integrated mass signal, IMS), and
      the modulation transfer function (MTF). RESULTS: The reconstructions of the
      scatter-corrected projections demonstrated superior image quality. The SDNR of
      masses embedded in a 5 cm thick tomosynthesis phantom improved 60%-66%, while the
      SDNR of the smallest mass in an 8 cm thick phantom improved by 59% (p < 0.01).
      The IMS of the masses in the 5 cm thick phantom also improved by 15%-29%, while
      the IMS of the masses in the 8 cm thick phantom improved by 26%-62% (p < 0.01).
      Some embedded microcalcifications in the tomosynthesis phantoms were visible only
      in the scatter-corrected reconstructions. The visibility of the findings in two
      patient images was also improved by the application of the scatter correction
      algorithm. The MTF of the images did not change after application of the scatter
      correction algorithm, indicating that spatial resolution was not adversely
      affected. CONCLUSIONS: Our software-based scatter correction algorithm exhibits
      great potential in improving the image quality of DBT acquisitions of both
      phantoms and patients. The proposed algorithm does not require a time-consuming
      MC simulation for each specific case to be corrected, making it applicable in the
      clinical realm.

PMID- 22149847
TI  - An approach to assessing stochastic radiogenic risk in medical imaging.
AB  - PURPOSE: This letter suggests a formalism, the medical effective dose (MED), that
      is suitable for assessing stochastic radiogenic risks in diagnostic medical
      procedures. METHODS: The MED is derived from radiobiological and probabilistic
      first principals, including: (1) The independence of radiation-induced biological
      effects in neighboring voxels at low doses; (2) the linear no-threshold
      assumption for stochastic radiation injury (although other dose-response
      relationships could be incorporated, instead); (3) the best human radiation dose
      response data currently available; and (4) the built-in possibility that the
      carcinogenic risk to an irradiated organ may depend on its volume. The MED
      involves a dose-risk summation over irradiated voxels at high spatial resolution;
      it reduces to the traditional effective dose when every organ is irradiated
      uniformly and when the dependence of risk on organ volumes is ignored. Standard
      relative-risk tissue weighting factors can be used with the MED approach until
      more refined data become available. RESULTS: The MED is intended for clinical and
      phantom dosimetry, and it provides an estimate of overall relative radiogenic
      stochastic risk for any given dose distribution. A result of the MED derivation
      is that the stochastic risk may increase with the volume of tissue (i.e., the
      number of cells) irradiated, a feature that can be activated when forthcoming
      radiobiological research warrants it. In this regard, the MED resembles neither
      the standard effective dose (E) nor the CT dose index (CTDI), but it is somewhat
      like the CT dose-length product (DLP). CONCLUSIONS: The MED is a novel,
      probabilistically and biologically based means of estimating stochastic-risk
      weighted doses associated with medical imaging. Built in, ab initio, is the
      ability to link radiogenic risk to organ volume and other clinical factors. It is
      straightforward to implement when medical dose distributions are available,
      provided that one is content, for the time being, to accept the relative tissue
      weighting factors published by the International Commission of Radiological
      Protection (ICRP). It requires no new radiobiological data and avoids major
      problems encountered by the E, CTDI, and CT-E formalisms. It makes possible
      relative inter-patient dosimetry, and also realistic intercomparisons of
      stochastic risks from different protocols that yield images of comparable
      quality.

PMID- 22149848
TI  - The simulation of 3D microcalcification clusters in 2D digital mammography and
      breast tomosynthesis.
AB  - PURPOSE: This work proposes a new method of building 3D models of
      microcalcification clusters and describes the validation of their realistic
      appearance when simulated into 2D digital mammograms and into breast
      tomosynthesis images. METHODS: A micro-CT unit was used to scan 23 breast biopsy
      specimens of microcalcification clusters with malignant and benign
      characteristics and their 3D reconstructed datasets were segmented to obtain 3D
      models of microcalcification clusters. These models were then adjusted for the x
      ray spectrum used and for the system resolution and simulated into 2D projection
      images to obtain mammograms after image processing and into tomographic sequences
      of projection images, which were then reconstructed to form 3D tomosynthesis
      datasets. Six radiologists were asked to distinguish between 40 real and 40
      simulated clusters of microcalcifications in two separate studies on 2D
      mammography and tomosynthesis datasets. Receiver operating characteristic (ROC)
      analysis was used to test the ability of each observer to distinguish between
      simulated and real microcalcification clusters. The kappa statistic was applied
      to assess how often the individual simulated and real microcalcification clusters
      had received similar scores ("agreement") on their realistic appearance in both
      modalities. This analysis was performed for all readers and for the real and the
      simulated group of microcalcification clusters separately. "Poor" agreement would
      reflect radiologists' confusion between simulated and real clusters, i.e.,
      lesions not systematically evaluated in both modalities as either simulated or
      real, and would therefore be interpreted as a success of the present models.
      RESULTS: The area under the ROC curve, averaged over the observers, was 0.55 (95%
      confidence interval [0.44, 0.66]) for the 2D study, and 0.46 (95% confidence
      interval [0.29, 0.64]) for the tomosynthesis study, indicating no statistically
      significant difference between real and simulated lesions (p > 0.05). Agreement
      between allocated lesion scores for 2D mammography and those for the
      tomosynthesis series was poor. CONCLUSIONS: The realistic appearance of the 3D
      models of microcalcification clusters, whether malignant or benign clusters, was
      confirmed for 2D digital mammography images and the breast tomosynthesis
      datasets; this database of clusters is suitable for use in future observer
      performance studies related to the detectability of microcalcification clusters.
      Such studies include comparing 2D digital mammography to breast tomosynthesis and
      comparing different reconstruction algorithms.

PMID- 22149849
TI  - Quantifying the tibiofemoral joint space using x-ray tomosynthesis.
AB  - PURPOSE: Digital x-ray tomosynthesis (DTS) has the potential to provide 3D
      information about the knee joint in a load-bearing posture, which may improve
      diagnosis and monitoring of knee osteoarthritis compared with projection
      radiography, the current standard of care. Manually quantifying and visualizing
      the joint space width (JSW) from 3D tomosynthesis datasets may be challenging.
      This work developed a semiautomated algorithm for quantifying the 3D tibiofemoral
      JSW from reconstructed DTS images. The algorithm was validated through
      anthropomorphic phantom experiments and applied to three clinical datasets.
      METHODS: A user-selected volume of interest within the reconstructed DTS volume
      was enhanced with 1D multiscale gradient kernels. The edge-enhanced volumes were
      divided by polarity into tibial and femoral edge maps and combined across kernel
      scales. A 2D connected components algorithm was performed to determine candidate
      tibial and femoral edges. A 2D joint space width map (JSW) was constructed to
      represent the 3D tibiofemoral joint space. To quantify the algorithm accuracy, an
      adjustable knee phantom was constructed, and eleven posterior-anterior (PA) and
      lateral DTS scans were acquired with the medial minimum JSW of the phantom set to
      0-5 mm in 0.5 mm increments (VolumeRadTM, GE Healthcare, Chalfont St. Giles,
      United Kingdom). The accuracy of the algorithm was quantified by comparing the
      minimum JSW in a region of interest in the medial compartment of the JSW map to
      the measured phantom setting for each trial. In addition, the algorithm was
      applied to DTS scans of a static knee phantom and the JSW map compared to values
      estimated from a manually segmented computed tomography (CT) dataset. The
      algorithm was also applied to three clinical DTS datasets of osteoarthritic
      patients. RESULTS: The algorithm segmented the JSW and generated a JSW map for
      all phantom and clinical datasets. For the adjustable phantom, the estimated
      minimum JSW values were plotted against the measured values for all trials. A
      linear fit estimated a slope of 0.887 (R2 = 0.962) and a mean error across all
      trials of 0.34 mm for the PA phantom data. The estimated minimum JSW values for
      the lateral adjustable phantom acquisitions were found to have low correlation to
      the measured values (R2 = 0.377), with a mean error of 2.13 mm. The error in the
      lateral adjustable-phantom datasets appeared to be caused by artifacts due to
      unrealistic features in the phantom bones. JSW maps generated by DTS and CT
      varied by a mean of 0.6 mm and 0.8 mm across the knee joint, for PA and lateral
      scans. The tibial and femoral edges were successfully segmented and JSW maps
      determined for PA and lateral clinical DTS datasets. CONCLUSIONS: A semiautomated
      method is presented for quantifying the 3D joint space in a 2D JSW map using
      tomosynthesis images. The proposed algorithm quantified the JSW across the knee
      joint to sub-millimeter accuracy for PA tomosynthesis acquisitions. Overall, the
      results suggest that x-ray tomosynthesis may be beneficial for diagnosing and
      monitoring disease progression or treatment of osteoarthritis by providing
      quantitative images of JSW in the load-bearing knee.

PMID- 22149850
TI  - Technical Note: modification of the standard gain correction algorithm to
      compensate for the number of used reference flat frames in detector performance
      studies.
AB  - PURPOSE: The x-ray performance evaluation of digital x-ray detectors is based on
      the calculation of the modulation transfer function (MTF), the noise power
      spectrum (NPS), and the resultant detective quantum efficiency (DQE). The flat
      images used for the extraction of the NPS should not contain any fixed pattern
      noise (FPN) to avoid contamination from nonstochastic processes. The "gold
      standard" method used for the reduction of the FPN (i.e., the different gain
      between pixels) in linear x-ray detectors is based on normalization with an
      average reference flat-field. However, the noise in the corrected image depends
      on the number of flat frames used for the average flat image. The aim of this
      study is to modify the standard gain correction algorithm to make it independent
      on the used reference flat frames. METHODS: Many publications suggest the use of
      10-16 reference flat frames, while other studies use higher numbers (e.g., 48
      frames) to reduce the propagated noise from the average flat image. This study
      quantifies experimentally the effect of the number of used reference flat frames
      on the NPS and DQE values and appropriately modifies the gain correction
      algorithm to compensate for this effect. RESULTS: It is shown that using the
      suggested gain correction algorithm a minimum number of reference flat frames
      (i.e., down to one frame) can be used to eliminate the FPN from the raw flat
      image. This saves computer memory and time during the x-ray performance
      evaluation. CONCLUSIONS: The authors show that the method presented in the study
      (a) leads to the maximum DQE value that one would have by using the conventional
      method and very large number of frames and (b) has been compared to an
      independent gain correction method based on the subtraction of flat-field images,
      leading to identical DQE values. They believe this provides robust validation of
      the proposed method.

PMID- 22149851
TI  - Development of a novel quality assurance system based on rolled-up and rolled-out
      radiochromic films in volumetric modulated arc therapy.
AB  - PURPOSE: To develop a cylindrical phantom with rolled-up radiochromic films and
      dose analysis software in the rolled-out plane for quality assurance (QA) in
      volumetric modulated arc therapy (VMAT). METHODS: The phantom consists of an
      acrylic cylindrical body wrapped with radiochromic film inserted into an outer
      cylindrical shell of 5 cm thickness. The rolled-up films with high spatial
      resolution enable detection of specific dose errors along the arc trajectory of
      continuously irradiated and modulated beams in VMAT. The developed dose analysis
      software facilitates dosimetric evaluation in the rolled-up and rolled-out planes
      of the film; the calculated doses on the corresponding points where the rolled-up
      film was placed were reconstructed into a rectangular dose matrix equivalent to
      that of the rolled-out plane of the film. The VMAT QA system was implemented in 3
      clinical cases of prostate, nasopharynx, and pelvic metastasis. Each calculated
      dose on the rolled-out plane was compared with measurement values by modified
      gamma evaluation. Detected positions of dose disagreement on the rolled-out plane
      were also distinguished in cylindrical coordinates. The frequency of error
      occurrence and error distribution were summarized in a histogram and in an axial
      view of rolled-up plane to intuitively identify the corresponding positions of
      detected errors according to the gantry angle. RESULTS: The dose matrix
      reconstructed from the developed VMAT QA system was used to verify the measured
      dose distribution along the arc trajectory. Dose discrepancies were detected on
      the rolled-out plane and visualized on the calculated dose matrix in cylindrical
      coordinates. The error histogram obtained by gamma evaluation enabled
      identification of the specific error frequency at each gantry angular position.
      The total dose error occurring on the cylindrical surface was in the range of 5%
      8% for the 3 cases. CONCLUSIONS: The developed system provides a practical and
      reliable QA method to detect dosimetric errors according to the gantry angle.
      Film dosimetry based on rolled-up and rolled-out techniques leads to dose
      verification in the subspaces of the 3D dose volume. The system can be employed
      as an alternative tool to detect the pitfalls of planar dose verification.

PMID- 22149852
TI  - 4D Cone-beam CT reconstruction using a motion model based on principal component
      analysis.
AB  - PURPOSE: To provide a proof of concept validation of a novel 4D cone-beam CT
      (4DCBCT) reconstruction algorithm and to determine the best methods to train and
      optimize the algorithm. METHODS: The algorithm animates a patient fan-beam CT
      (FBCT) with a patient specific parametric motion model in order to generate a
      time series of deformed CTs (the reconstructed 4DCBCT) that track the motion of
      the patient anatomy on a voxel by voxel scale. The motion model is constrained by
      requiring that projections cast through the deformed CT time series match the
      projections of the raw patient 4DCBCT. The motion model uses a basis of
      eigenvectors that are generated via principal component analysis (PCA) of a
      training set of displacement vector fields (DVFs) that approximate patient
      motion. The eigenvectors are weighted by a parameterized function of the patient
      breathing trace recorded during 4DCBCT. The algorithm is demonstrated and tested
      via numerical simulation. RESULTS: The algorithm is shown to produce accurate
      reconstruction results for the most complicated simulated motion, in which voxels
      move with a pseudo-periodic pattern and relative phase shifts exist between
      voxels. The tests show that principal component eigenvectors trained on DVFs from
      a novel 2D/3D registration method give substantially better results than
      eigenvectors trained on DVFs obtained by conventionally registering 4DCBCT phases
      reconstructed via filtered backprojection. CONCLUSIONS: Proof of concept testing
      has validated the 4DCBCT reconstruction approach for the types of simulated data
      considered. In addition, the authors found the 2D/3D registration approach to be
      our best choice for generating the DVF training set, and the Nelder-Mead simplex
      algorithm the most robust optimization routine.

PMID- 22149853
TI  - Accurate calibration method for 3D freehand ultrasound probe using virtual plane.
AB  - PURPOSE: In this paper a new, easy-to-manufacture and easy-to-use ultrasound (US)
      probe calibration phantom for 3D freehand scanning is presented and evaluated,
      together with a new method for achieving an accurate and user-robust calibration
      using virtual plane. METHODS: The phantom allows the optically tracked US probe
      to perform two rotations and two translations while keeping the image of a
      tensioned wire in the image plane. This approach allows obtaining a sharp image
      of the wire independently from the probe pose. The virtual plane allows the
      calibration algorithm to converge minimizing the required number of US probe
      tracked poses. The US image and position data are synchronized via a CORBA
      interface, created within the Image Guided Surgery Toolkit (IGSTK) framework. The
      calibration algorithm and the calibration protocol were evaluated in a set of
      experiments carried out by different test-users. RESULTS: The calibration method
      proved to be accurate and precise: 3D point reconstruction accuracy resulted 0.2
      mm as mean value, while the precision was 0.4 mm as standard deviation.
      CONCLUSIONS: The technique showed to be suitable for medical applications from
      morphological diagnosis to intraoperative surgical planning adaption.

PMID- 22149854
TI  - Comparison of air-kerma strength determinations for HDR (192)Ir sources.
AB  - PURPOSE: To perform a comparison of the interim air-kerma strength standard for
      high dose rate (HDR) (192)Ir brachytherapy sources maintained by the University
      of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL) with
      measurements of the various source models using modified techniques from the
      literature. The current interim standard was established by Goetsch et al. in
      1991 and has remained unchanged to date. METHODS: The improved, laser-aligned
      seven-distance apparatus of the University of Wisconsin Medical Radiation
      Research Center (UWMRRC) was used to perform air-kerma strength measurements of
      five different HDR (192)Ir source models. The results of these measurements were
      compared with those from well chambers traceable to the original standard.
      Alternative methodologies for interpolating the (192)Ir air-kerma calibration
      coefficient from the NIST air-kerma standards at (137)Cs and 250 kVp x rays
      (M250) were investigated and intercompared. As part of the interpolation method
      comparison, the Monte Carlo code EGSnrc was used to calculate updated values of
      A(wall) for the Exradin A3 chamber used for air-kerma strength measurements. The
      effects of air attenuation and scatter, room scatter, as well as the solution
      method were investigated in detail. RESULTS: The average measurements when using
      the inverse N(K) interpolation method for the Classic Nucletron, Nucletron
      microSelectron, VariSource VS2000, GammaMed Plus, and Flexisource were found to
      be 0.47%, -0.10%, -1.13%, -0.20%, and 0.89% different than the existing standard,
      respectively. A further investigation of the differences observed between the
      sources was performed using MCNP5 Monte Carlo simulations of each source model
      inside a full model of an HDR 1000 Plus well chamber. CONCLUSIONS: Although the
      differences between the source models were found to be statistically significant,
      the equally weighted average difference between the seven-distance measurements
      and the well chambers was 0.01%, confirming that it is not necessary to update
      the current standard maintained at the UWADCL.

PMID- 22149855
TI  - Toward a better understanding of the gamma index: Investigation of parameters
      with a surface-based distance method.
AB  - PURPOSE: The purpose of this work was to clarify the interactions between the
      parameters used in the gamma index with the surface-based distance method, which
      itself can be viewed as a generalized version of the gamma index. The examined
      parameters included the distance to agreement (DTA)/dose difference (DD)
      criteria, the percentage used as a passing criterion, and the passing percentage
      for given DTA/DD criteria. The specific aims of our work were (1) to understand
      the relationships between the parameters used in the gamma index, (2) to
      determine the detection limit, or the minimum detectable error, of the gamma
      index with a given set of parameters, and (3) to establish a procedure to
      determine parameters that are consistent with the capacity of an IMRT QA system.
      METHODS: The surface-based distance technique with dose gradient factor was
      derived, and then the relationship between surface-based distance and gamma index
      was established. The dose gradient factor for plans and measurements of 10 IMRT
      patients, 10 spine stereotactic radiosurgery (SRS) patients, and 3 Radiological
      Physics Center (RPC) head and neck phantom were calculated and evaluated. The
      detection limits of the surface-based distance and gamma index methods were
      examined by introducing known shifts to the 10 IMRT plans. RESULTS: The means of
      the dose gradient factors were 0.434 mm/% and 0.956 mm/% for the SRS and IMRT
      plans, respectively. Key quantities (including the mean and 90th and 99th
      percentiles of the distance distribution) of the surface-based distance
      distribution between two dose distributions were linearly proportional to the
      actual shifts. However, the passing percentage of the gamma index for a given set
      of DTA/DD criteria was not associated with the actual shift. For IMRT, using the
      standard quality assurance criteria of 3 mm/3% DTA/DD and a 90% passing rate, we
      found that the detection limit of the gamma index in terms of global shift was
      4.07 mm/4.07 % without noise. CONCLUSIONS: Surface-based distance is a direct
      measure of the difference between two dose distributions and can be used to
      evaluate or determine parameters for use in calculating the gamma index. The dose
      gradient factor represents the weighting between spatial and dose shift and
      should be determined before DTA/DD criteria are set. The authors also present a
      procedure to determine gamma index parameters from measurements.

PMID- 22149856
TI  - An electromagnetic navigation system for transbronchial interventions with a
      novel approach to respiratory motion compensation.
AB  - PURPOSE: Bronchoscopic interventions, such as transbronchial needle aspiration
      (TBNA), are commonly performed procedures to diagnose and stage lung cancer.
      However, due to the complex structure of the lung, one of the main challenges is
      to find the exact position to perform a biopsy and to actually hit the biopsy
      target (e.g., a lesion). Today, most interventions are accompanied by fluoroscopy
      to verify the position of the biopsy instrument, which means additional radiation
      exposure for the patient and the medical staff. Furthermore, the diagnostic yield
      of TBNA is particularly low for peripheral lesions. METHODS: To overcome these
      problems the authors developed an image-guided, electromagnetic navigation system
      for transbronchial interventions. The system provides real time positioning
      information for the bronchoscope and a transbronchial biopsy instrument with only
      one preoperatively acquired computed tomography image. A twofold respiratory
      motion compensation method based on a particle filtering approach allows for
      guidance through the entire respiratory cycle. In order to evaluate our system,
      18 transbronchial interventions were performed in seven ventilated swine lungs
      using a thorax phantom. RESULTS: All tracked bronchoscope positions were
      corrected to the inside of the tracheobronchial tree and 80.2% matched the
      correct bronchus. During regular respiratory motion, the mean overall targeting
      error for bronchoscope tracking and TBNA needle tracking was with compensation on
      10.4 +/- 1.7 and 10.8 +/- 3.0 mm, compared to 14.4 +/- 1.9 and 13.3 +/- 2.7 mm
      with compensation off. The mean fiducial registration error (FRE) was 4.2 +/- 1.1
      mm. CONCLUSIONS: The navigation system with the proposed respiratory motion
      compensation method allows for real time guidance during bronchoscopic
      interventions, and thus could increase the diagnostic yield of transbronchial
      biopsy.

PMID- 22149857
TI  - Commissioning a small-field biological irradiator using point, 2D, and 3D
      dosimetry techniques.
AB  - PURPOSE: To commission a small-field biological irradiator, the XRad225Cx from
      Precision x-Ray, Inc., for research use. The system produces a 225 kVp x-ray beam
      and is equipped with collimating cones that produce both square and circular
      radiation fields ranging in size from 1 to 40 mm. This work incorporates point,
      2D, and 3D measurements to determine output factors (OF), percent-depth-dose
      (PDD) and dose profiles at multiple depths. METHODS: Three independent dosimetry
      systems were used: ion-chambers (a farmer chamber and a micro-ionisation
      chamber), 2D EBT2 radiochromic film, and a novel 3D dosimetry system
      (DLOS/PRESAGE(r)). Reference point dose rates and output factors were determined
      from in-air ionization chamber measurements for fields down to ~13 mm using the
      formalism of TG61. PDD, profiles, and output factors at three separate depths (0,
      0.5, and 2 cm), were determined for all field sizes from EBT2 film measurements
      in solid water. Several film PDD curves required a scaling correction, reflecting
      the challenge of accurate film alignment in very small fields. PDDs, profiles,
      and output factors were also determined with the 3D DLOS/PRESAGE(r) system which
      generated isotropic 0.2 mm data, in scan times of 20 min. RESULTS: Surface output
      factors determined by ion-chamber were observed to gradually drop by ~9% when the
      field size was reduced from 40 to 13 mm. More dramatic drops were observed for
      the smallest fields as determined by EBT~18% and ~42% for the 2.5 mm and 1 mm
      fields, respectively. PRESAGE(r) and film output factors agreed well for fields
      <20 mm (where 3D data were available) with mean deviation of 2.2% (range 1%-4%).
      PDD values at 2 cm depth varied from ~72% for the 40 mm field, down to ~55% for
      the 1 mm field. EBT and PRESAGE(r) PDDs agreed within ~3% in the typical therapy
      region (1-4 cm). At deeper depths the EBT curves were slightly steeper (2.5% at 5
      cm). These results indicate good overall consistency between ion-chamber, EBT2
      and PRESAGE(r) measured OFs, PDDs, and profiles. CONCLUSIONS: The combination of
      independent 2D and 3D measurements was found to be valuable to ensure accurate
      and comprehensive commissioning. Film measurements were time consuming and
      challenging due to the difficulty of film alignment in small fields. PRESAGE(r)
      3D measurements were comprehensive and efficient, because alignment errors are
      negligible, and all parameters for multiple fields could be obtained from a
      single dosimeter and scan. However, achieving accurate superficial data (within 4
      mm) is not yet feasible due to optical surface artifacts.

PMID- 22149858
TI  - A new water-equivalent 2D plastic scintillation detectors array for the dosimetry
      of megavoltage energy photon beams in radiation therapy.
AB  - PURPOSE: The objective of this work is to present a new 2D plastic scintillation
      detectors array (2D-PSDA) designed for the dosimetry of megavoltage (MV) energy
      photon beams in radiation therapy and to characterize its basic performance.
      METHODS: We developed a 2D detector array consisting of 781 plastic scintillation
      detectors (PSDs) inserted into a plane of a water-equivalent phantom. The PSDs
      were distributed on a 26 * 26 cm(2) grid, with an interdetector spacing of 10 mm,
      except for two perpendicular lines centered on the detection plane, where the
      spacing was 5 mm. Each PSD was made of a 1 mm diameter by 3 mm long cylindrical
      polystyrene scintillating fiber coupled to a clear nonscintillating plastic
      optical fiber. All of the light signals emitted by the PSDs were read
      simultaneously with an optical system at a rate of one measurement per second. We
      characterized the performance of the optical system, the angular dependency of
      the device, and the perturbation of dose distributions caused by the hundreds of
      PSDs inserted into the phantom. We also evaluated the capacity of the system to
      monitor complex multileaf collimator (MLC) sequences such as those encountered in
      step-and-shoot intensity modulated radiation therapy (IMRT) plans. We compared
      our results with calculations performed by a treatment planning system and with
      measurements taken with a 2D ionization chamber array and with a radiochromic
      film. RESULTS: The detector array that we developed allowed us to measure doses
      with an average precision of better than 1% for cumulated doses equal to or
      greater than 6.3 cGy. Our results showed that the dose distributions produced by
      the 6-MV photon beam are not perturbed (within +/-1.1%) by the presence of the
      hundreds of PSDs located into the phantom. The results also showed that the
      variations in the beam incidences have little effect on the dose response of the
      device. For all incidences tested, the passing rates of the gamma tests between
      the 2D-PSDA and the treatment planning system were higher than 97.5% when the
      standard clinical tolerances of 3% or 3 mm were used. Excellent agreement was
      obtained between the doses measured and calculated when we used the 2D-PSDA for
      monitoring a MLC sequence from a step-and-shoot IMRT plan. CONCLUSIONS: We
      demonstrated the feasibility of using a large number of PSDs in a new 2D-PSDA for
      the dosimetry of MV energy photon beams in radiation therapy. The excellent
      precision, accuracy, and low angular dependence of the device indicate that such
      a prototype could potentially be used as a high-accuracy quality assurance tool
      for IMRT and arc therapy patient plan verification. The homogeneity and water
      equivalence of the prototype we built suggest that this technology could be
      extended to multiple detection planes by arranging the fibers into more complex
      orientations, opening the possibility for 3D dosimetry with PSDs.

PMID- 22149859
TI  - Fully 3D list-mode time-of-flight PET image reconstruction on GPUs using CUDA.
AB  - PURPOSE: List-mode processing is an efficient way of dealing with the sparse
      nature of positron emission tomography (PET) data sets and is the processing
      method of choice for time-of-flight (ToF) PET image reconstruction. However, the
      massive amount of computation involved in forward projection and backprojection
      limits the application of list-mode reconstruction in practice, and makes it
      challenging to incorporate accurate system modeling. METHODS: The authors present
      a novel formulation for computing line projection operations on graphics
      processing units (GPUs) using the compute unified device architecture (CUDA)
      framework, and apply the formulation to list-mode ordered-subsets expectation
      maximization (OSEM) image reconstruction. Our method overcomes well-known GPU
      challenges such as divergence of compute threads, limited bandwidth of global
      memory, and limited size of shared memory, while exploiting GPU capabilities such
      as fast access to shared memory and efficient linear interpolation of texture
      memory. Execution time comparison and image quality analysis of the GPU-CUDA
      method and the central processing unit (CPU) method are performed on several data
      sets acquired on a preclinical scanner and a clinical ToF scanner. RESULTS: When
      applied to line projection operations for non-ToF list-mode PET, this new GPU
      CUDA method is >200 times faster than a single-threaded reference CPU
      implementation. For ToF reconstruction, we exploit a ToF-specific optimization to
      improve the efficiency of our parallel processing method, resulting in GPU
      reconstruction >300 times faster than the CPU counterpart. For a typical whole
      body scan with 75 * 75 * 26 image matrix, 40.7 million LORs, 33 subsets, and 3
      iterations, the overall processing time is 7.7 s for GPU and 42 min for a single
      threaded CPU. Image quality and accuracy are preserved for multiple imaging
      configurations and reconstruction parameters, with normalized root mean squared
      (RMS) deviation less than 1% between CPU and GPU-generated images for all cases.
      CONCLUSIONS: A list-mode ToF OSEM library was developed on the GPU-CUDA platform.
      Our studies show that the GPU reformulation is considerably faster than a single
      threaded reference CPU method especially for ToF processing, while producing
      virtually identical images. This new method can be easily adapted to enable more
      advanced algorithms for high resolution PET reconstruction based on additional
      information such as depth of interaction (DoI), photon energy, and point spread
      functions (PSFs).

PMID- 22149860
TI  - Comment on "in-patient to isocenter KERMA ratios in CT" [Med. Phys. 38, 5362-5369
      (2011)].

PMID- 22149862
TI  - Scientific journals and impact factors.

PMID- 22149863
TI  - The tenuous state of clinical medical physics in diagnostic imaging.

PMID- 22149864
TI  - Special Issue for the 6th IEEE international conference on Nano/Micro engineered
      and molecular systems (IEEE-NEMS 2011).

PMID- 22149865
TI  - Nanochannel system fabricated by MEMS microfabrication and atomic force
      microscopy.
AB  - A silicon nanochannel system with integrated transverse electrodes was designed
      and fabricated by combining micro-electro-mechanical systems (MEMS)
      micromachining and atomic force microscopy (AFM)-based nanolithography. The
      fabrication process began with the patterning of microscale reservoirs and
      electrodes on an oxidised silicon chip using conventional MEMS techniques. A
      nanochannel, approximately 30 [micro sign]m long with a small semi-circular cross
      sectional area of 20 nm * 200 nm, was then mechanically machined on the oxide
      surface between the micro reservoirs by applying AFM nanolithography with an all
      diamond probe. Anodic bonding was used to seal off the nanochannel with a
      matching Pyrex cover. Continuous flow in the nanochannel was verified by
      pressurising a solution of fluorescein isothiocyanate in ethanol through the
      nanochannel in a vacuum chamber. It was further demonstrated by translocating
      negatively charged nanobeads (diameter approximately 20 nm) through the
      nanochannel by using an external DC electric field. The passage of the nanobeads
      caused a sharp increase in the transverse electrical conductivity of the
      nanochannel.

PMID- 22149866
TI  - Development of a low-cost magnetic microfluidic chip for circulating tumour cell
      capture.
AB  - The authors have developed a novel fabrication process for a selective micro
      magnetic activated cell sorting (MACS) chip based on ferromagnetic material
      encapsulated micropillars (FMEMs), which is technically simple and low cost. The
      FMEM produces a high field gradient to magnetically attract, capture and hold
      cells on its interface. System test simulations were carried out to predict the
      efficacy of target capture and verify that the actual magnetic particles
      behaviour agreed well with model predictions. To determine the ability of the
      novel microMACS chip to capture circulating tumour cells (CTCs), SW620 human
      colon cancer cells were used in an in vitro flow model system and were able to be
      captured with the efficiency of 72.8%. The obvious accumulation of CTCs at a
      certain location on the chip suggested shear stress events at the pillar boundary
      may influence efficacy, and should be considered in further optimisation efforts.

PMID- 22149867
TI  - Viscosity-density sensor with resonant torsional paddle for direct detection in
      liquid.
AB  - A novel micro-machined biosensor based on the resonant torsional paddle with
      electromagnetic excitation which can work in liquid directly is presented. The
      sensor designed consists of two paddles with resonant torsional mode, in which
      the energy loss of the resonator during the vibration is so lower that it can be
      suitable for detection in liquid. Finite element method analysis was carried out
      to guarantee the sensitivity of the sensor. Micro electro-mechanical system
      (MEMS) bulk silicon processes were adopted to accomplish the fabrication. A
      positive-feedback circuit with energy compensation is designed to improve the
      characteristics of the sensor in liquid. Experiments show that the resonant
      torsional paddle can work directly in liquid and the Q-factor of the sensor in
      liquid can be improved from 2.65 to 40 with energy compensation. Viscosity tests
      and density tests for the sensor show that the decrease in frequency and the
      decrease in Q-factor are related to density and viscosity of the solutions,
      respectively.

PMID- 22149868
TI  - Portable potentiostatic sensor integrated with neopterin-imprinted poly(ethylene
      co-vinyl alcohol)-based electrode.
AB  - Neopterin is a catabolic product of guanosine triphosphate, a purine nucleotide.
      Measuring neopterin concentrations in biological fluids such as urine provides
      information about cellular immune activation in humans under control of T helper
      cells. A high neopterin concentration in bodily fluids, including serum and
      urine, indicates cellular immunity activation, which is associated with oxidative
      stress. In this work, neopterin is the target molecule and imprinted onto
      poly(ethylene-co-vinyl alcohol) via solvent evaporation. The template molecules
      on the thin film are then removed, and the membrane is used as a sensing element
      for electrochemical urinalysis. Poly(ethylene-co-vinyl alcohol) containing 27
      mol% ethylene had high imprinting effectiveness and may be integrated with the
      proposed portable biosensor. In random urine analysis, the cyclic voltammetry
      measurements of neopterin with an additional recovery method achieved >95%
      recovery for the neopterin concentration of 15 ng/mL.

PMID- 22149869
TI  - DNA as a template in self-assembly of Au nano-structure.
AB  - In this study, an alkanethiol-assisted self-assembly of Au nano-particles and its
      size tunable technique were confirmed. To fabricate a one-dimensional (1D)
      template, -DNA was first laid on mica substrate by dropping diluted -DNA
      solution, 12.6 ng/[micro sign]l, on freshly cleaved mica. By dropping colloidal
      gold solution on mica surface with the DNA templates laid on it, the -DNA was
      then pulled straight via capillary force by applying solvent absorbing tissue at
      outer circumference of the mica substrate. Moreover, it fixed on mica via gravity
      force and Van der Waals force between mica surface and the DNA. Au nano-particles
      would be arrayed along the straight DNA molecules to form 1D Au arrays. Then
      based on the synthesis of 1D nano-structure via DNA template and Au nano
      particles, the simple 2D nano-structure, a ring, would also be studied.

PMID- 22149870
TI  - XPS and NEXAFS studies of VUV/O3-treated aromatic polyurea and its application to
      microchip electrophoresis.
AB  - In this study, the authors performed X-ray photoelectron spectroscopy (XPS) and
      near-edge X-ray absorption fine structure (NEXAFS) studies of vacuum ultraviolet
      (VUV)/O3-treated aromatic polyurea films to investigate their treatment effects.
      XPS and NEXAFS spectra indicate that the benzene ring was cleaved after treatment
      and that carboxyl, hydroxyl, ketone and aldehyde groups were formed at the
      cleaved sites. The VUV/O3-treated polyurea film was applied to a
      polymethylmethacrylate (PMMA) microchip for microchip electrophoresis (MCE) of
      bovine serum albumin (BSA). Fast electro-osmotic mobility of 4.6*10(-4) cm2/V/s
      as well as reduction of the BSA adhesion was achieved. This functional surface is
      useful for high-speed MCE analysis.

PMID- 22149871
TI  - Wireless and batteryless biomedical microsystem for neural recording and epilepsy
      suppression based on brain focal cooling.
AB  - This work presents a biomedical microsystem with a wireless radiofrequency (RF)
      powered electronics and versatile sensors/actuators for use in nanomedicinal
      diagnosis and therapy. The cooling of brain tissue has the potential to reduce
      the frequency and severity of epilepsy. Miniaturised spiral coils as a wireless
      power module with low-dropout linear regulator circuit convert RF signals into a
      DC voltage, can be implanted without a battery in monitoring free behaviour. A
      thermoelectric (TE) cooler is an actuator that is employed to cool down brain
      tissue to suppress epilepsy. Electroencephalogram (EEG) electrodes and TE coolers
      are integrated to form module that is placed inside the head of a rat and
      fastened with a bio-compatible material. EEG signals are used to identify
      waveforms associated with epilepsy and are measured using readout circuits. The
      wireless part of the presented design achieves a low quiescent current and
      line/load regulation and high antenna/current efficiency with thermal protection
      to avoid damage to the implanted tissue. Epilepsy is suppressed by reducing the
      temperature to reduce the duration of this epileptic episode. Related
      characterisations demonstrate that the proposed design can be adopted in an
      effective nanomedicine microsystem.

PMID- 22149872
TI  - Experiment and simulation of resistance of nanoporous dentin biomaterial to CO2
      laser irradiation.
AB  - The resistance of nanoporous dentin biomaterial to CO2 laser irradiation was
      investigated by experiment and simulation for potential tooth hypersensitivity
      treatment. The controlled parameters including laser power of 0.03-0.150 W,
      scanning speeds of 11.4-34.2 mm/s and focus/defocus modes were used for studying
      interaction between laser energy and dentin of human tooth. Most of the dentin
      specimens were etched after CO2 laser irradiation with the power larger than 0.12
      W at a scanning speed of 11.4 mm/s. Compared with the simulation results of
      temperature distribution, the maximum temperature at laser powers from 0.12 to
      0.15 W is increased from 1961 to 2245 degrees C, which exceeded the melting point
      (1570 degrees C) of dentin's main content hydroxyapatite (HA). Increasing
      scanning speed can reduce the linear density of laser output energy for just
      locally melting porous microstructure of dentin surface without etching. Varying
      focus mode can also improve the damage of nanoporous dentin microstructure. At
      parameters of 0.150 W power and 34.2 mm/s scanning speed under defocus operation,
      laser treatment was successfully performed on the nano-HA coated dentin with well
      molten sealing on tubules of porous microstructure at a simulate surface
      temperature of about 574 degrees C, which was the potential for dentin
      hypersensitivity cure application.

PMID- 22149873
TI  - Digital microfluidic operations on micro-electrode dot array architecture.
AB  - As digital microfluidics-based biochips find more applications, their complexity
      is expected to increase significantly owing to the trend of multiple and
      concurrent assays on the chip. There is a pressing need to deliver a top-down
      design methodology that the biochip designer can leverage the same level of
      computer-aided design support as the semi-conductor industry now does. Moreover,
      as microelectronics fabrication technology is scaling up and integrated device
      performance is improving, it is expected that these microfluidic biochips will be
      integrated with microelectronic components in next-generation system-on-chip
      designs. This study presents the analysis and experiments of digital microfluidic
      operations on a novel electrowetting-on-dielectric-based 'micro-electrode dot
      array architecture' that fosters a development path for hierarchical top-down
      design approach for digital microfluidics. The proposed architecture allows
      dynamic configurations and activations of identical basic microfluidic unit
      called 'micro-electrode cells' to design microfluidic components, layouts,
      routing, microfluidic operations and applications of the biochip hierarchically.
      Fundamental microfluidic operations have been successfully performed by the
      architecture. In addition, this novel architecture demonstrates a number of
      advantages and flexibilities over the conventional digital microfluidics in
      performing advanced microfluidic operations.

PMID- 22149874
TI  - HER2 therapy--an abundance of riches.

PMID- 22149877
TI  - Impact factor on the rise.

PMID- 22149883
TI  - The hydrolyzed products of iridoid glycoside with beta-glucosidase treatment
      exert anti-proliferative effects through suppression of STAT3 activation and
      STAT3-regulated gene products in several human cancer cells.
AB  - CONTEXT: Iridoids belong to a group of monoterpene compounds with cyclopentane
      ring and found as mostly the glycoside forms in nature. They act primarily as the
      defense substances and found in various medicinal plants. OBJECTIVE: Although
      many iridoids exhibit anti-inflammatory and anticancer activities, their
      molecular targets/pathways are not fully understood. Here, the antiproliferative
      effect of the hydrolyzed-iridoid product (H-iridoid) form through the STAT3
      signaling pathways on tumor cells was investigated. MATERIALS AND METHODS: H
      iridoids were obtained from five iridoid glycosides with beta-glucosidase
      treatment. The effects of several H-iridoids on cell viability and cell
      proliferation in tumor cells were measured by the MTT assay. The phosphorylation
      levels of STAT3, its regulatory molecules, and apoptosis by H-geniposide
      treatment in DU145 cells were investigated by immunoblots and flow cytometry.
      RESULTS: No single iridoid glycoside exerted any cytotoxicity in the tumor cells,
      whereas H-iridoids had significant cytotoxic, antiproliferative, and STAT3
      inhibitory effects and revealed different potencies depending on their chemical
      structures. Among the H-iridoids tested, H-geniposide inhibited constitutive
      STAT3 activation through inhibiting upstream JAK1 and c-Src. Consistent with
      STAT3 inactivation, H-geniposide downregulated the expressions of Bcl-2, Bcl-xL,
      survivin, and cyclin D1; this correlated with the accumulation of cells in the
      sub-G1 phase of the cell cycle and the induction of apoptosis. DISCUSSION AND
      CONCLUSIONS: Our results indicate that the hydrolysis of the glycosidic bond from
      iridoid glycoside is required for exhibiting cytotoxicity in tumor cells. H
      geniposide is the most potent agent and a novel blocker of STAT3 activation in
      DU145 cells.

PMID- 22149876
TI  - Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.
AB  - BACKGROUND: Resistance to endocrine therapy in breast cancer is associated with
      activation of the mammalian target of rapamycin (mTOR) intracellular signaling
      pathway. In early studies, the mTOR inhibitor everolimus added to endocrine
      therapy showed antitumor activity. METHODS: In this phase 3, randomized trial, we
      compared everolimus and exemestane versus exemestane and placebo (randomly
      assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced
      breast cancer who had recurrence or progression while receiving previous therapy
      with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat
      advanced disease (or both). The primary end point was progression-free survival.
      Secondary end points included survival, response rate, and safety. A preplanned
      interim analysis was performed by an independent data and safety monitoring
      committee after 359 progression-free survival events were observed. RESULTS:
      Baseline characteristics were well balanced between the two study groups. The
      median age was 62 years, 56% had visceral involvement, and 84% had hormone
      sensitive disease. Previous therapy included letrozole or anastrozole (100%),
      tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade
      3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group
      vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4%
      vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs.
      0%). At the interim analysis, median progression-free survival was 6.9 months
      with everolimus plus exemestane and 2.8 months with placebo plus exemestane,
      according to assessments by local investigators (hazard ratio for progression or
      death, 0.43; 95% confidence interval [CI], 0.35 to 0.54; P<0.001). Median
      progression-free survival was 10.6 months and 4.1 months, respectively, according
      to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001).
      CONCLUSIONS: Everolimus combined with an aromatase inhibitor improved progression
      free survival in patients with hormone-receptor-positive advanced breast cancer
      previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis;
      BOLERO-2 ClinicalTrials.gov number, NCT00863655.).

PMID- 22149884
TI  - Degradation of cyanobacterial biosignatures by ionizing radiation.
AB  - Primitive photosynthetic microorganisms, either dormant or dead, may remain today
      on the martian surface, akin to terrestrial cyanobacteria surviving
      endolithically in martian analog sites on Earth such as the Antarctic Dry Valleys
      and the Atacama Desert. Potential markers of martian photoautotrophs include the
      red edge of chlorophyll reflectance spectra or fluorescence emission from systems
      of light-harvesting pigments. Such biosignatures, however, would be modified and
      degraded by long-term exposure to ionizing radiation from the unshielded cosmic
      ray flux onto the martian surface. In this initial study into this issue, three
      analytical techniques--absorbance, reflectance, and fluorescence spectroscopy-
      were employed to determine the progression of the radiolytic destruction of
      cyanobacteria. The pattern of signal loss for chlorophyll reflection and
      fluorescence from several biomolecules is characterized and quantified after
      increasing exposures to ionizing gamma radiation. This allows estimation of the
      degradation rates of cyanobacterial biosignatures on the martian surface and the
      identification of promising detectable fluorescent break-down products.

PMID- 22149885
TI  - Endurance to physical strain in patients with temporomandibular disorders: a case
      control study.
AB  - OBJECTIVE: The hypothesis tested was whether patients with temporomandibular
      disorders (TMD) have an impaired endurance to motor tasks, under physical strain.
      MATERIAL AND METHODS: The study population included 81 cases with TMD and 75
      controls. After giving their informed consent, the participants filled out a
      questionnaire and performed five endurance trials. Each trial was measured in
      seconds from start to termination. The tests included: (a) holding the arm in a
      straight out position with a 2 kg weight in the hand, (b) lifting and lowering
      the arm with a 2 kg weight in the hand, (c) opening and closing the mandible
      repeatedly against a resistance of 1.6 kg during the jaw-opening phase, (d)
      protruding and retracting the mandible repeatedly against a resistance of 1.6 kg
      during the protruding phase and (e) unilateral chewing of three pieces of chewing
      gum. Analysis of differences between cases and controls for endurance were
      evaluated with Mann-Whitney U-test. A p-value < 0.05 was considered statistically
      significant. RESULTS: The cases had statistically significantly (p < 0.0001)
      lower endurance time than controls for all tests. CONCLUSIONS: Patients with TMD
      compared to those without signs and symptoms of TMD have an impaired capacity to
      endure motor tasks that involve physical demand of the jaw muscles and shoulder
      girdle muscles.

PMID- 22149875
TI  - Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.
AB  - BACKGROUND: The anti-human epidermal growth factor receptor 2 (HER2) humanized
      monoclonal antibody trastuzumab improves the outcome in patients with HER2
      positive metastatic breast cancer. However, most cases of advanced disease
      eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that
      inhibits receptor dimerization, has a mechanism of action that is complementary
      to that of trastuzumab, and combination therapy with the two antibodies has shown
      promising activity and an acceptable safety profile in phase 2 studies involving
      patients with HER2-positive breast cancer. METHODS: We randomly assigned 808
      patients with HER2-positive metastatic breast cancer to receive placebo plus
      trastuzumab plus docetaxel (control group) or pertuzumab plus trastuzumab plus
      docetaxel (pertuzumab group) as first-line treatment until the time of disease
      progression or the development of toxic effects that could not be effectively
      managed. The primary end point was independently assessed progression-free
      survival. Secondary end points included overall survival, progression-free
      survival as assessed by the investigator, the objective response rate, and
      safety. RESULTS: The median progression-free survival was 12.4 months in the
      control group, as compared with 18.5 months in the pertuzumab group (hazard ratio
      for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001).
      The interim analysis of overall survival showed a strong trend in favor of
      pertuzumab plus trastuzumab plus docetaxel. The safety profile was generally
      similar in the two groups, with no increase in left ventricular systolic
      dysfunction; the rates of febrile neutropenia and diarrhea of grade 3 or above
      were higher in the pertuzumab group than in the control group. CONCLUSIONS: The
      combination of pertuzumab plus trastuzumab plus docetaxel, as compared with
      placebo plus trastuzumab plus docetaxel, when used as first-line treatment for
      HER2-positive metastatic breast cancer, significantly prolonged progression-free
      survival, with no increase in cardiac toxic effects. (Funded by F. Hoffmann-La
      Roche/Genentech; ClinicalTrials.gov number, NCT00567190.).

PMID- 22149887
TI  - The ninth annual Ion Channel Retreat, Vancouver, Canada, June 27-29, 2011.
AB  - Nine years ago Aurora Biomed Inc. (Vancouver, Canada) committed to gathering the
      brightest minds and the most innovative research companies at one conference. The
      Ion Channel Retreat provides a podium for scientific discourse spanning a wide
      range of ion channel disciplines. This conference has consistently provided a
      venue for people to share knowledge, exchange ideas, and establish partnerships.
      This conference continues to expand and grow each year, demonstrating the value
      of such a conference. Attendees at the 2011 Ion Channel retreat presented ion
      channel research from 12 different countries, representing research groups
      located on 5 of the 7 continents. Aurora Biomed's 2011 Retreat covered a variety
      of topics including Ion Channels as Disease Targets, Ion Channels as Pain
      Targets, TRP-channels, Ion Channel Screening Technologies, Cardiac Function and
      Pharmacology, Cardiac Safety and Toxicology, and Structure and Function of Ion
      Channels.

PMID- 22149888
TI  - hERGCentral: a large database to store, retrieve, and analyze compound-human
      Ether-a-go-go related gene channel interactions to facilitate cardiotoxicity
      assessment in drug development.
AB  - The unintended and often promiscous inhibition of the cardiac human Ether-a-go-go
      related gene (hERG) potassium channel is a common cause for either delay or
      removal of therapeutic compounds from development and withdrawal of marketed
      drugs. The clinical manifestion is prolongation of the duration between QRS
      complex and T-wave measured by surface electrocardiogram (ECG)-hence Long QT
      Syndrome. There are several useful online resources documenting hERG inhibition
      by known drugs and bioactives. However, their utilities remain somewhat limited
      because they are biased toward well-studied compounds and their number of data
      points tends to be much smaller than many commercial compound libraries. The
      hERGCentral ( www.hergcentral.org ) is mainly based on experimental data obtained
      from a primary screen by electrophysiology against more than 300,000 structurally
      diverse compounds. The system is aimed to display and combine three resources:
      primary electrophysiological data, literature, as well as online reports and
      chemical library collections. Currently, hERGCentral has annotated datasets of
      more than 300,000 compounds including structures and chemophysiological
      properties of compounds, raw traces, and biophysical properties. The system
      enables a variety of query formats, including searches for hERG effects according
      to either chemical structure or properties, and alternatively according to the
      specific biophysical properties of current changes caused by a compound.
      Therefore, the hERGCentral, as a unique and evolving resource, will facilitate
      investigation of chemically induced hERG inhibition and therefore drug
      development.

PMID- 22149895
TI  - A selective, colorimetric, and fluorescent chemodosimeter for relay recognition
      of fluoride and cyanide anions based on 1,1'-binaphthyl scaffold.
AB  - The reaction-based relay recognition of fluoride and cyanide anions was
      demonstrated for the first time, with rapid response and unique triple
      (fluorescence color, intensity and absorption band) output modes in either of two
      sequential sensing events. Ratiometric determination of these two anions by
      fluorescence and/or absorbance spectra is also achieved.

PMID- 22149889
TI  - Organization and functional analysis of the 5' flanking regions of myostatin-1
      and 2 genes from Larimichthys crocea.
AB  - Myostatin (MSTN) is a negative regulator of skeletal muscle growth and
      development. There are two types of MSTNs in fish, but little is known about
      their gene regulation. Here, the 5' flanking fragments of 1029 bp from MSTN-1 and
      643 bp from MSTN-2 were cloned, sequenced, and analyzed in Larimichthys crocea.
      Both fragments contained CAAT box and several putative cis-regulatory elements.
      However, putative TATA box, MyoD, MEF3, SP1, USF, and GH-CSE sites were
      identified only in the L. crocea MSTN-1 (lcMSTN-1) promoter. Transcriptional
      activities of four fragments (1013, 841, 514, and 261 bp) truncated from lcMSTN-1
      upstream region and two fragments (643 and 296 bp) from lcMSTN-2 upstream region
      were examined in vitro, using transient transfection in CIK and L6 cells. In CIK
      cells, the promoter activity correlated positively with the length of truncated
      fragments in both MSTN-1 and 2. The lcMSTN-2 promoter showed a higher activity
      than lcMSTN-1 in the corresponding region, which was consistent with MSTN gene
      expression in vivo. In L6 cells, lcMSTN-2 upstream showed an extremely high
      luciferase activity. These data indicated that both cloned 5' flanking sequences
      contained functional promoters, and that transcription regulation of lcMSTN-1 and
      2 promoters was significantly different between mammalian and fish cells.

PMID- 22149896
TI  - Comparative study of normal and rheumatoid arthritis fibroblast-like synoviocytes
      proliferation under cyclic mechanical stretch: role of prostaglandin E2.
AB  - Fibroblast-like synoviocytes (FLSs) are one of the main contributors of
      prostaglandin E(2) (PGE(2)) in the hyperplastic synovium of rheumatoid arthritis
      (RA) patients. cyclooxygenase-2 (COX-2)/PGE(2) pathway is involved in the
      proliferation of several cell types. We have previously shown that mechanical
      stretch affects COX-2 and PGE(2) production in human RA FLSs; however, its role
      in cell proliferation remains to be elucidated. In this study, a comparison is
      drawn between human RA and normal FLSs to understand the role of mechanical
      stretch and PGE(2) on the proliferation of FLSs. The results showed that
      physiological level (6%, 1 Hz) of cyclic mechanical stretch significantly
      decreased the proliferation of RA FLSs but not normal FLSs, while the induction
      of apoptosis was not observed by stretch in either RA or normal FLSs. IL-1beta (5
      ng/ml)-induced COX-2/PGE(2) levels are downregulated by stretch in RA FLSs only.
      Further investigation showed that high concentration (100 and 500 ng/ml) of
      PGE(2) significantly induced cell proliferation only in RA FLSs, and this
      induction failed to be suppressed by stretch. In conclusion, this study
      demonstrated that elevated levels of PGE(2) in the synovial cavity are involved
      in the proliferation of RA FLSs, and cyclic mechanical stretch regulates the RA
      synovial hyperplasia.

PMID- 22149897
TI  - Sexual quality of life in patients undergoing coronary artery bypass graft
      surgery.
AB  - OBJECTIVES: Despite improvements in many domains of functioning, sexual quality
      of life often remains impaired following coronary artery bypass graft (CABG)
      surgery. This study examined associations among sexual quality of life, fear of
      sexual activity and receiving information from providers about sexual activity in
      CABG patients. METHODS: Participants completed a survey assessing sexual
      activity, mental health and physical health at baseline (3-5-day post-surgery;
      n=60) and 2-month post-surgery (n=42). RESULTS: Sexual quality of life showed
      moderate difficulties at baseline and did not improve by follow-up (p
      values>=0.09). At follow-up, greater patient fear was associated with lower
      sexual quality of life in some domains; receiving information was related to
      lower fear (p values<=0.03) and greater sexual satisfaction and interest (p
      values<=0.04). Suggestive of mediation, there was a significant indirect effect
      of information on patient fear and of patient fear on sexual interest (p=0.05).
      CONCLUSIONS: Though data were cross-sectional, findings suggest that fears of
      sexual activity may play a role in lowering CABG patients' motivation for sexual
      activity and that receiving information from a medical provider may assist in
      hastening sexual rehabilitation. Prospective and intervention studies are needed
      to support findings.

PMID- 22149898
TI  - Characterisation and genetic polymorphism of metallothionein gene CgMT4 in
      experimental families of Pacific oyster Crassostrea gigas displaying summer
      mortality.
AB  - Summer mortality events have been observed in Pacific oyster Crassostrea gigas
      for several decades. This paper examines the selective pressure exerted by summer
      mortality on the polymorphism of a newly identified oyster metallothionein gene.
      CgMT4 cDNA and genomic sequences were obtained. CgMT4 was studied in two
      generations of oysters reared in three sites on the French Atlantic coast, using
      single strand conformation polymorphism analysis. Four alleles were detected.
      Individuals carrying genotype MT4-CD seem to have higher susceptibility to summer
      risk conditions. The MT4 gene could be a potential new genetic marker for
      susceptibility; further validation studies are recommended.

PMID- 22149899
TI  - Radical scavenging-linked antioxidant activities of commonly used herbs and
      spices in Korea.
AB  - Herbs and spices not only variety and racy flavour to Korean foods, they also are
      the richest source for antioxidant power. The present study evaluates the radical
      scavenging-linked antioxidant activities of hot water extracts from commonly used
      herbs and spices in Korea. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical and
      superoxide anion scavenging activities of bay extract were 39.5% and 22.1%,
      respectively. The hydroxyl radical scavenging activity was in order of dill
      (50.0%) > bay (31.3%) > garlic (27.9%) > white pepper and black pepper (15.1
      15.3%) > onion (10.1%) extracts. Bay extract had the highest total phenolic
      content (17.86 MUg CE/g). High correlation coefficients were found between the
      total phenol content and DPPH radical scavenging activity (R = 0.9162). These
      results indicate that herbs and spices had high antioxidant activity that is
      partly due to the phenolic compounds and provide basic data for further
      development of processed food products.

PMID- 22149900
TI  - Determinants of the intention to use condoms in a sample of French adolescents.
AB  - OBJECTIVE: To identify the determinants of the intention to use and actual use of
      condoms in a sample of French adolescents based on Ajzen's Theory of Planned
      Behaviour. METHOD: Two-hundred-and-thirty French secondary-school students (mean
      age: 17.68 years; SD = 1.08) completed a questionnaire about condom use
      intention. RESULTS: 'Perceived behavioural control', 'individual attitudes',
      'subjective socio-cultural norms' and 'subjective norms of close friends and
      relatives' are the main factors explaining 33% of variance of condom use
      intention. For girls, intention is essentially associated with perceived control,
      subjective norms ('close friends and relatives', and then, 'socio-cultural
      norms') and individual attitudes, whereas for boys, it is more closely linked to
      individual attitudes and to subjective socio-cultural norms. The best predictors
      of the intention to use a condom are perceived control and individual attitudes
      for girls while, for boys, individual attitudes come before perceived control.
      CONCLUSION: In order to design effective programmes for prevention of sexually
      transmitted infections, the determinants of the intention to use condoms must be
      considered.

PMID- 22149901
TI  - The tenth anniversary of metabolic syndrome and related disorders.

PMID- 22149902
TI  - What facilitates the entry of persons with disabilities into South African
      companies?
AB  - PURPOSE: The persistent high unemployment rate for persons with disabilities
      (PWDs) is a world-wide concern. The aim of this research was to identify
      facilitating factors for the entry of PWDs into the labour market. METHOD: A
      survey of Human Resources (HR) managers in South African (SA) companies was
      conducted to explore what would assist with hiring PWDs. The sample population of
      companies was identified through the Marketline Library database and supplemented
      with all Johannesburg Stock Exchange companies. This rendered a population size
      of 348. RESULTS: A response rate of 25% (86) was achieved. Companies that have
      appointed PWDs in the past seem more willing to appoint PWDs in the future.
      Companies value information on accommodation (preparation of the environment and
      cost) and the impact of disability on job performance most. The use of
      specialised recruitment agencies, the development of targeted recruitment plans
      and staff sensitisation training, as well as internships are perceived as the
      best facilitators for the employment of PWDs. CONCLUSIONS: Rehabilitation
      practitioners can inform PWDs on the best strategies for approaching companies.
      Companies with facilitating factors already in place may also be more willing to
      employ PWDs and rehabilitation practitioners can target these companies as future
      employers of PWDs.

PMID- 22149903
TI  - A patient-centered pharmacy services model of HIV patient care in community
      pharmacy settings: a theoretical and empirical framework.
AB  - Reflecting trends in health care delivery, pharmacy practice has shifted from a
      drug-specific to a patient-centered model of care, aimed at improving the quality
      of patient care and reducing health care costs. In this article, we outline a
      theoretical model of patient-centered pharmacy services (PCPS), based on in
      depth, qualitative interviews with a purposive sample of 28 pharmacists providing
      care to HIV-infected patients in specialty, semispecialty, and nonspecialty
      pharmacy settings. Data analysis was an interactive process informed by
      pharmacists' interviews and a review of the general literature on patient
      centered care, including Medication Therapy Management (MTM) services. Our main
      finding was that the current models of pharmacy services, including MTM, do not
      capture the range of pharmacy services in excess of mandated drug dispensing
      services. In this article, we propose a theoretical PCPS model that reflects the
      actual services pharmacists provide. The model includes five elements: (1)
      addressing patients as whole, contextualized persons; (2) customizing
      interventions to unique patient circumstances; (3) empowering patients to take
      responsibility for their own health care; (4) collaborating with clinical and
      nonclinical providers to address patient needs; and (5) developing sustained
      relationships with patients. The overarching goal of PCPS is to empower patients'
      to take responsibility for their own health care and self-manage their HIV
      infection. Our findings provide the foundation for future studies regarding how
      widespread these practices are in diverse community settings, the validity of the
      proposed PCPS model, the potential for standardizing pharmacist practices, and
      the feasibility of a PCPS framework to reimburse pharmacists services.

PMID- 22149904
TI  - Silymarin, a molecule of interest for topical photoprotection.
AB  - Some UV-filters have side effects. For example, oestrogenic effect was
      demonstrated for 4-methylbenzylidene camphor. Given that secondary metabolites
      are known for their UVB photoprotective properties in plants that contain them,
      we chose to study silymarin as an agent which could potentially be used in sun
      products. This determination is based on the physical determination of the
      reduction of the energy in the UV range, through a film of product which has
      previously been spread on an adequate substrate. About 15 mg of O/W emulsion
      containing silymarin at various concentrations was applied on roughened PMMA
      plates and the transmission measurements were carried out using a
      spectrophotometer equipped with integrating sphere. Incorporated in O/W creams,
      at a concentration of 10% (w/w), silymarin gives a Sun Protection Factor similar
      to that of octylmethoxicinnamate, which is why it is predominantly used in
      Europe. Overall, these results demonstrate that silymarin is a promising new
      sunscreen agent.

PMID- 22149905
TI  - Effect of intravitreal bevacizumab (Avastin((r))) therapy in malignant
      hypertensive retinopathy: a report of two cases.
AB  - PURPOSE: Malignant hypertensive retinopathy is a rare, but serious, complication
      of uncontrolled systemic hypertension for which no treatment has been established
      yet. We report 2 patients with malignant hypertensive retinopathy who recovered
      promptly following intravitreal bevacizumab injection. METHODS: Intravitreal
      bevacizumab (1.25 mg/0.05 mL) was injected in 4 eyes of 2 patients having
      malignant hypertensive retinopathy with optic disc edema, macular edema, and
      retinal exudates. A complete ophthalmic examination, including the best-corrected
      visual acuity (BCVA), central macular thickness (CMT) on optical coherence
      tomography (OCT), and fluorescein angiography (FAG), was performed before and
      after the treatments. RESULTS: Two eyes in 1 patient received two intravitreal
      injections of bevacizumab, whereas 2 eyes in the other patient received a single
      treatment. All 4 eyes had improvement of macular edema on OCT at 1 month and
      decreased fluorescein leakage on FAG 3 months after the treatment, which led to
      improvements in the BCVA in 3 eyes. In 1 eye with foveal atrophy, no change in
      the BCVA occurred despite the improved macular edema on OCT. CONCLUSIONS: The
      results suggest that intravitreal bevacizumab injections might be a useful
      adjunctive treatment of malignant hypertensive retinopathy in some selected
      cases. However, further studies are mandatory to determine the safety and the
      efficacy of such injections in this disease.

PMID- 22149906
TI  - Role of magnetic resonance cholangiopancreatography for choledocholithiasis:
      analysis of patients with negative MRCP.
AB  - OBJECTIVE: To investigate the negative predictive value of magnetic resonance
      cholangiopancreatography (MRCP) for common bile duct (CBD) stones and the
      prognosis of patients suspected to have choledocholithiasis in whom the MRCP was
      negative for CBD stones. METHODS: We enrolled the patients suspected to have
      choledocholithiasis in whom the MRCP was negative for the CBD stones between
      January 2008 and March 2011 and retrospectively analyzed the outcomes of 115
      patients. RESULTS: Endoscopic retrograde cholangiopancreatography (ERCP) was
      performed in 27 patients (23%, group 1), and none had CBD stones. The negative
      predictive value of MRCP was 100%. During a median follow-up of 18.3 months,
      acute cholangitis with newly developed CBD stones occurred in two patients.
      Eighty-eight patients (77%, group 2) did not undergo ERCP and all recovered from
      acute cholangitis without CBD surgery. During a median follow-up of 18.7 months,
      acute cholangitis, acute cholecystitis, gallstone pancreatitis, and pancreatico
      biliary cancers occurred in four (4.6%), three (3.5%), one (1.2%), and three
      (3.5%) patients, respectively. New CBD stones were found in only two patients
      among four patients with recurrent acute cholangitis. No patient had recurrent
      cholangitis caused by MRCP-missed CBD stones. The rates of recurrent cholangitis
      and cholangitis-free survival did not differ between groups 1 and 2. CONCLUSION:
      The negative predictive value of MRCP was very high. ERCP can be reserved for
      patients who are MRCP negative for choledocholithiasis, but close follow-up is
      needed because of recurrent cholangitis or pancreatico-biliary cancer.

PMID- 22149908
TI  - Flow rate and flow equation of pharmaceutical free-flowable powder excipients.
AB  - Basic aspect of powder handling is powder flow which depends on mechanical
      properties of the solid material. This experimental work presents the results of
      flowability testing of the free-flowable particle size fraction of 0.0250-0.0315
      cm of five powder excipients. The single-point determination of the mass flow
      rate from a cylindrical, flat-bottomed hopper was primarily influenced by the
      diameter of a circular orifice. The significant effect of the orifice height was
      also noted. Increasing the orifice height, the flow under gravity is directed
      resulting in the sudden acceleration of the flow rate. The critical zone relates
      to the orifice diameter. The multi-point determination of flowability employed
      the actual parameters of the flow equation which allows the prediction of the
      mass flow rate. The precision of the prediction was the basic criterion in
      optimization of the orifice geometry. Based on the results, the orifice height of
      1.6 cm can be recommended for the correction of faster powder flow. For the
      slower powder flow, an orifice height of 0.2 cm can be used alternatively. In
      conclusion, the information about the orifice height used should be referred to
      whenever test the powder flowability and compare the results.

PMID- 22149909
TI  - Toward an exploration of feeling of strangeness in schizophrenia: perspectives on
      acousmatic and everyday listening.
AB  - The aim of this study was to investigate abnormal perceptual experiences in
      schizophrenia, in particular the feeling of strangeness, which is commonly found
      in patients' self-reports. The experimental design included auditory complex
      stimuli within 2 theoretical frameworks based on "sensory gating deficit" and
      "aberrant salience," inspired from conventional perceptual scales. A specific
      sound corpus was designed with environmental (meaningful) and abstract
      (meaningless) sounds. The authors compared sound evaluations on 3 perceptual
      dimensions (bizarre, familiar, and invasive) and 2 emotional dimensions
      (frightening and reassuring) between 20 patients with schizophrenia (SCZ) and 20
      control participants (CTL). The perceptual judgment was rated on independent
      linear scales for each sound. In addition, the conditioning-testing P50 paradigm
      was conducted on 10 SCZ and 10 CTL. Both behavioral and electrophysiological data
      confirmed the authors' expectations according to the 2 previous theoretical
      frameworks and showed that abnormal perceptual experiences in SCZ consisted of
      perceiving meaningful sounds in a distorted manner and as flooding/inundating but
      also in perceiving meaningless sounds as things that become meaningful by
      assigning them some significance. In addition, the use of independent scales to
      each perceptual dimension highlighted an unexpected ambivalence on familiarity
      and bizarreness in SCZ compatible with the explanation of semantic process
      impairment. The authors further suggested that this ambivalence might be due to a
      conflicting coactivation of 2 types of listening, that is, every day and musical
      (or acousmatic) listening.

PMID- 22149910
TI  - The covariation of trait anger and borderline personality: a bivariate twin
      siblings study.
AB  - Anger can be defined as an emotion consisting of feelings of variable intensity,
      from mild irritation or annoyance to intense fury and rage. Borderline
      personality disorder (BPD) is characterized by impulsivity and instability of
      interpersonal relationships, of self-image, and of negative affects. Borderline
      personality and trait anger are often observed together. The present study
      examined the extent to which a genetic association explains the covariation
      between a trait measure of borderline personality and trait anger. To this end,
      self-report data of 5,457 twins and 1,487 of their siblings registered with the
      Netherlands Twin Register and the East Flanders Prospective Twin Survey were
      analyzed using genetic structural equation modeling. A significant phenotypic
      correlation was observed between the two traits (rP = .52). This correlation was
      explained by genetic (54%) and by environmental influences (46%). A shared
      genetic risk factor is thus one of the explanations for the covariation of
      borderline personality and trait anger.

PMID- 22149912
TI  - Tactile perceptual processes and their relationship to somatoform disorders.
AB  - The Somatic Signal Detection Task (SSDT) is a recent paradigm serving to examine
      perceptual processes likely relevant for somatoform disorders. We tested whether
      touch illusions are more easily induced in individuals suffering from somatoform
      disorders (SFD) and whether their perceptual threshold for tactile stimuli is
      lower compared to healthy controls. Thirty-three participants with SFD and 32
      healthy controls reported whether they recognized near-threshold tactile stimuli
      at their fingertip, which were presented in half of the test trials. With a
      probability of 0.5, an auxiliary visual stimulus was additionally presented.
      Tactile detection thresholds, tactile sensitivity, response bias, and the rate of
      false-positive perceptions of the tactile stimulus were assessed. In both groups,
      the light stimulus led to an amelioration of tactile sensitivity as well as to a
      more liberal response style. The SFD group was characterized by a more liberal
      response bias in the first half of the light-absent condition compared to the
      healthy controls. Within the SFD group, the report of somatoform (especially
      pseudoneurological) symptoms correlated positively with illusory tactile
      perceptions in the SSDT. Tactile thresholds in the SSDT were measured reliably
      (rtt = .86) and were significantly lower in the SFD group. The notion that
      general perceptual dispositions influence the formation of symptom perception may
      thus complement cognitive models of SFD.

PMID- 22149911
TI  - Aberrant paralimbic gray matter in criminal psychopathy.
AB  - Psychopaths impose large costs on society, as they are frequently habitual,
      violent criminals. The pervasive nature of emotional and behavioral symptoms in
      psychopathy suggests that several associated brain regions may contribute to the
      disorder. Studies employing a variety of methods have converged on a set of brain
      regions in paralimbic cortex and limbic areas that appear to be dysfunctional in
      psychopathy. The present study further tests this hypothesis by investigating
      structural abnormalities using voxel-based morphometry in a sample of
      incarcerated men (N=296). Psychopathy was associated with decreased regional gray
      matter in several paralimbic and limbic areas, including bilateral
      parahippocampal, amygdala, and hippocampal regions, bilateral temporal pole,
      posterior cingulate cortex, and orbitofrontal cortex. The consistent
      identification of paralimbic cortex and limbic structures in psychopathy across
      diverse methodologies strengthens the interpretation that these regions are
      crucial for understanding neural dysfunction in psychopathy.

PMID- 22149913
TI  - On "risk" and reward: investigating state anhedonia in psychometrically defined
      schizotypy and schizophrenia.
AB  - Anhedonia, defined as dysfunction in the experience of pleasant emotions, is a
      hallmark symptom of the schizophrenia spectrum. Of interest, it is well
      documented that patients with schizophrenia, at least as a group, do not show
      reductions in their state experience of pleasant stimuli. However, there is
      emerging evidence to suggest that individuals with schizotypy--defined as the
      personality organization reflecting the latent vulnerability for schizophrenia-
      do show these state deficits. This is paradoxical in that schizophrenia reflects
      a more pathological state in virtually every conceivable domain as compared with
      schizotypy. The present study examined self-reported affective reactions to
      neutral-, bad-, and good-valenced stimuli in individuals with psychometrically
      defined schizotypy and schizophrenia. Two separate control groups were also
      included, comprising psychometrically defined controls and stable outpatients
      with affective disorders. With no exceptions, the schizotypy group reported
      significantly less pleasant affect for each of the three conditions than each of
      the other groups. Conversely, the schizophrenia group did not statistically
      differ from the control groups for any of the conditions. Within both the
      schizotypy and schizophrenia groups, severity of negative symptoms/traits was
      associated with less pleasant report. We found that individuals with prominent
      negative symptoms and traits from the schizophrenia and schizotypy groups
      resembled each other in terms of state anhedonia. The present findings did not
      appear to reflect comorbid depression or anxiety. Our discussion centers on this
      apparent paradox in the schizophrenia spectrum--that individuals with schizotypy
      exhibit state anhedonia, whereas patients with schizophrenia do not.

PMID- 22149914
TI  - An extensive phase space for the potential martian biosphere.
AB  - We present a comprehensive model of martian pressure-temperature (P-T) phase
      space and compare it with that of Earth. Martian P-T conditions compatible with
      liquid water extend to a depth of ~310 km. We use our phase space model of Mars
      and of terrestrial life to estimate the depths and extent of the water on Mars
      that is habitable for terrestrial life. We find an extensive overlap between
      inhabited terrestrial phase space and martian phase space. The lower martian
      surface temperatures and shallower martian geotherm suggest that, if there is a
      hot deep biosphere on Mars, it could extend 7 times deeper than the ~5 km depth
      of the hot deep terrestrial biosphere in the crust inhabited by hyperthermophilic
      chemolithotrophs. This corresponds to ~3.2% of the volume of present-day Mars
      being potentially habitable for terrestrial-like life.

PMID- 22149920
TI  - Chemotherapy alone for early-stage Hodgkin's lymphoma.

PMID- 22149922
TI  - Influence of various types of damage on the fracture strength of ceramic femoral
      heads.
AB  - Ceramic-on-ceramic articulations are a frequently used bearing for total hip
      replacements. This success mainly is due to their excellent tribological
      properties. Ceramics can withstand high pressure loads due to its brittleness but
      only low bending stresses. A ceramic ball head fracture is the result of
      subcritical crack growth. This kind of fracture in vivo can abet by damage or
      contamination of the stem cone. The main goal of this work is to provide a risk
      assessment of different possible damage mechanisms and contaminations that may
      result in lower fracture strength of a ceramic ball head. To simulate potential
      causes, different types and dimensions of metal wire, foils, hair, and lubricants
      were inserted between the ceramic ball head and the metal cone of the stem. The
      test results clearly show that fracture strength is negatively influenced by most
      of the inhomogeneities between the cone and the head because they increase the
      peak stresses acting on a part of the ceramic ball head. The results of this
      article clearly confirm the demand for an undamaged taper fit "free of
      contamination" between the ceramic head and the metal cone during implantation.

PMID- 22149921
TI  - ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma.
AB  - BACKGROUND: Chemotherapy plus radiation treatment is effective in controlling
      stage IA or IIA nonbulky Hodgkin's lymphoma in 90% of patients but is associated
      with late treatment-related deaths. Chemotherapy alone may improve survival
      because it is associated with fewer late deaths. METHODS: We randomly assigned
      405 patients with previously untreated stage IA or IIA nonbulky Hodgkin's
      lymphoma to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine
      (ABVD) alone or to treatment with subtotal nodal radiation therapy, with or
      without ABVD therapy. Patients in the ABVD-only group, both those with a
      favorable risk profile and those with an unfavorable risk profile, received four
      to six cycles of ABVD. Among those assigned to subtotal nodal radiation therapy,
      patients who had a favorable risk profile received subtotal nodal radiation
      therapy alone and patients with an unfavorable risk profile received two cycles
      of ABVD plus subtotal nodal radiation therapy. The primary end point was 12-year
      overall survival. RESULTS: The median length of follow-up was 11.3 years. At 12
      years, the rate of overall survival was 94% among those receiving ABVD alone, as
      compared with 87% among those receiving subtotal nodal radiation therapy (hazard
      ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to
      0.99; P=0.04); the rates of freedom from disease progression were 87% and 92% in
      the two groups, respectively (hazard ratio for disease progression, 1.91; 95% CI,
      0.99 to 3.69; P=0.05); and the rates of event-free survival were 85% and 80%,
      respectively (hazard ratio for event, 0.88; 95% CI, 0.54 to 1.43; P=0.60). Among
      the patients randomly assigned to ABVD alone, 6 patients died from Hodgkin's
      lymphoma or an early treatment complication and 6 died from another cause; among
      those receiving radiation therapy, 4 deaths were related to Hodgkin's lymphoma or
      early toxic effects from the treatment and 20 were related to another cause.
      CONCLUSIONS: Among patients with Hodgkin's lymphoma, ABVD therapy alone, as
      compared with treatment that included subtotal nodal radiation therapy, was
      associated with a higher rate of overall survival owing to a lower rate of death
      from other causes. (Funded by the Canadian Cancer Society and the National Cancer
      Institute; HD.6 ClinicalTrials.gov number, NCT00002561.).

PMID- 22149923
TI  - Can contextual online exams in practical biomedical education increase
      comprehension and motivation?: a pilot project.
AB  - The exclusive reproduction of short-term learned and pool-based contents in
      examinations may impede development of in-depth understanding. This pilot project
      suggests an approach useful to overcome this shortcoming by enhancing students'
      motivation for comprehensive learning using automatically added contextual
      questions in electronic examinations. Installed in practical courses teaching
      pain physiology, digital data acquisition and examination workstations were
      interlinked via a network connection. The data acquisition software was
      substantiated by algorithms that evaluated data acquired before their
      transmission to examination workstations. These data were used by the assessment
      software operating on these workstations to automatically compose new examination
      questions. Examinations thus combined pool questions with newly generated
      questions with authentic digitized data from the preceding course. This helped
      confront students with questions based on their individual data that had resulted
      from the courses examined. Formative evaluation showed an increase in motivation
      and alertness for practical tasks and acquired results. This suggests usefulness
      of this setting in examining the preparation and comprehension of course
      contents. There is reason to assume that this approach is suitable to be
      transferred to other practical courses using digital acquisition of practical and
      examination data.

PMID- 22149924
TI  - Prion peptide PrP106-126 induces inducible nitric oxide synthase and
      proinflammatory cytokine gene expression through the activation of NF-kappaB in
      macrophage cells.
AB  - The inflammatory response in prion diseases is dominated by microglia activation.
      The molecular mechanisms that lie behind this inflammatory process are not very
      well understood. In the present study, we examined the activat2ion of nuclear
      factor-kappa B (NF-kappaB) upon exposure to PrP106-126 and its role in PrP106-126
      induced upregulation of inducible nitric oxide synthase (iNOS) and
      proinflammatory cytokines (interleukin [IL]-1beta, tumor necrosis factor [TNF]
      alpha, IL-6) in Ana-1 macrophages. The results showed that iNOS and
      proinflammatory cytokine release was significantly elevated in Ana-1 macrophages
      upon exposure to PrP106-126; that PrP106-126 treatment led to a significant NF
      kappaB activation; that proinflammatory cytokines gene expression was elevated in
      macrophages upon exposure to PrP106-126; and that NF-kappaB inhibition
      significantly abrogated PrP106-126-induced upregulation of iNOS and inflammatory
      cytokine mRNA expression. These results suggest that treatment with neurotoxic
      prion peptides leads to the activation of transcription factor NF-kappaB, which
      in turn stimulates gene expression of iNOS and proinflammatory cytokines in Ana-1
      macrophages.

PMID- 22149926
TI  - Xuhuai goat H-FABP gene clone, subcellular localization of expression products
      and the preparation of transgenic mice.
AB  - The aim of this study was to clone the heart-type fatty acid binding protein (H
      FABP) gene of Xuhuai goat, to explore it bioinformatically, and analyze the
      subcellular localization using enhanced green fluorescent protein (EGFP). The
      results showed that the coding sequence (CDS) length of Xuhuai goat H-FABP gene
      was 402 bp, encoding 133 amino acids (GenBank accession number AY466498.1). The H
      FABP cDNA coding sequence was compared with the corresponding region of human,
      chicken, brown rat, cow, wild boar, donkey, and zebrafish. The similarity were
      89%, 76%, 85%, 84%, 93%, 91%, 70%, respectively. For the corresponding amino acid
      sequences, the similarity were 90%, 79%, 88%, 97%, 95%, 94%, 72%, respectively.
      This study did not find the signal peptide region in the H-FABP protein; it
      revealed that H-FABP protein might be a nonsecreted protein. H-FABP expression
      was detected in vitro by reverse transcription-polymerase chain reaction (RT
      PCR), and the EGFP-H-FABP fusion protein was localized to the cytoplasm. The gene
      could also be transiently and permanently expressed in mice.

PMID- 22149927
TI  - Cell-free DNA as a marker for prediction of brain damage in traumatic brain
      injury in rats.
AB  - Traumatic brain injury (TBI) is a major cause of morbidity and mortality, and
      early predictors of neurological outcomes are of great clinical importance. Cell
      free DNA (CFD), a biomarker used for the diagnosis and monitoring of several
      diseases, has been implicated as a possible prognostic indicator after TBI. The
      purpose of this study was to determine the pattern and timing of CFD levels after
      TBI, and whether a relationship exists between the level of CFD and brain edema
      and neurological outcomes. Thirty-nine Sprague-Dawley rats were randomly assigned
      to two groups: rats in group 1 (sham group) were anesthetized and had a scalp
      incision without TBI, and rats in group 2 were anesthetized and had a scalp
      incision with TBI, which was induced by using a weight drop model that causes
      diffuse brain injury. A neurological severity score (NSS) was assessed at 1, 24,
      and 48 h after TBI. CFD was measured via blood samples drawn at t=0 (baseline),
      12, 24, 48, 72, and 120 h after TBI. At 48 h after TBI, brain edema was
      determined in a subgroup of 11 rats by calculating the difference between rats'
      wet and dry brain weight. The significance of comparisons between and within
      groups (CFD levels, brain water content, and NSS) were determined using the
      Kruskal-Wallis, Mann-Whitney and Student t test. The correlation between CFD
      levels and the NSS, as well as between CFD levels and the extent of brain edema,
      was calculated using the Spearman and Pearson tests, respectively. Compared with
      baseline levels, the CFD levels in rats subjected to TBI were significantly
      increased at 24 and 48 h after TBI (p<0.01 and p<0.05, respectively). A positive
      correlation was demonstrated between CFD levels 24 h following TBI and the extent
      of brain edema (r=0.63, p<0.05), as well as between CFD levels and the NSS
      (r=0.79, p<0.005). In this study, we demonstrated an increase in CFD levels after
      TBI, as well as a correlation between CFD levels and brain edema and NSS. CFD
      levels may provide a quick, reliable, and simple prognostic indicator of
      neurological outcome in animals after TBI. Its role in humans has not been
      clearly elucidated, but has potentially significant clinical implications.

PMID- 22149929
TI  - Comparison of different treatment modalities for oral halitosis.
AB  - OBJECTIVES: To assess the effects on intra-oral halitosis by a mouth rinse
      containing zinc acetate (0.3%) and chlorhexidine diacetate (0.025%) with and
      without adjunct tongue scraping. MATERIALS AND METHODS: Twenty-one subjects
      without a diagnosis of periodontitis were randomized in a cross-over clinical
      trial. Organoleptic scores (OLS) were assessed to define intra-oral halitosis by
      total volatile sulfur compound (T-VSC) measurements and by gas chromatography.
      RESULTS: Twenty-one subjects with a mean age of 45.7 years (SD: +/-13.3, range:
      21-66). The OLS were significantly lower following active rinse combined with
      tongue scraping (p < 0.001) at all time points. Immediately after, at 30 min, and
      at day 14, the T-VSC values were lower in the active rinse sequence than in the
      negative rinse sequence (p < 0.001, p < 0.001 and p < 0.05, respectively). At 30
      min and at day 14, the hydrogen sulfide (H(2)S) and methyl mercaptan (MM) values
      were lower in the active rinse sequence compared to the inactive rinse sequence
      (p < 0.001). The inactive rinse sequence with tongue scraping reduced T-VSC at 30
      min (p < 0.001) but not at 14 days. Similar reductions in T-VSC, H(2)S and MM
      were found in the active rinse sequence with or without tongue scraping.
      CONCLUSION: The use of a tongue scraper did not provide additional benefits to
      the active mouth rinse, but reduced OLS and tongue coating index.

PMID- 22149928
TI  - Aerosolized clindamycin is superior to aerosolized dexamethasone or clindamycin
      dexamethasone combination in the treatment of severe Porphyromonas gingivalis
      aspiration pneumonia in an experimental murine model.
AB  - Adjunctive corticosteroid treatment to reduce excessive local inflammatory
      response in pneumonia is controversial. To study the effects of an early local
      adjunct dexamethasone treatment on the course of pneumonia and
      inflammatory/cytokine response, mice were intratracheally inoculated with live
      Porphyromonas gingivalis and treated with either clindamycin (C), dexamethasone
      (D), C+D combination, or were not treated (Pg). Six mice from each group were
      euthanized at 6, 24, 72, and 168 hours after inoculation. Levels of tumor
      necrosis factor (TNF)-alpha, soluble TNF-alpha receptors (sTNFR1 and sTNFR2),
      interleukin (IL)-1beta, and IL-6 in the serum and lung-homogenate supernatant
      were determined. Lung samples were histopathologically assessed and all findings
      compared to those found in 24 sham-inoculated mice (phosphate-buffered saline
      [PBS]). Severe P. gingivalis-induced bronchopneumonia progressed from 24 hours,
      peaked at 72 hours, and resolved after 168 hours with changes in local and
      systemic cytokine levels. Clindamycin-treated mice developed only mild
      bronchopneumonia that resolved fast (72 hours) with an early (6-24 hours)
      normalization of local and systemic cytokine levels. Similar course of pneumonia
      and cytokine level changes were observed in mice treated with C+D, but later.
      Early (6-24 hours) local elevation of sTNFRs was observed in C and C+D groups of
      mice, whereas nontreated (Pg) mice had increased systemic sTNFRs. Severe
      bronchopneumonia with delayed resolution was observed in D-group mice, with an
      early local and systemic decrease in sTNFR1 and persistent elevation of local TNF
      alpha. Clindamycin or a clindamycin-dexamethasone combination treatment
      significantly improves the course of P. gingivalis-aspiration pneumonia, but more
      so if clindamycin alone is used. A favorable course of pneumonia seems to be
      associated with an early elevation of sTNFRs and normalization of TNF-alpha.

PMID- 22149930
TI  - Design and analysis of braid-twist collagen scaffolds.
AB  - Collagen type I fiber-based scaffolds for anterior cruciate ligament (ACL)
      replacement were evaluated for their mechanical properties and their ability to
      promote cellular proliferation. Prior to scaffold formation, two crosslinking
      methods were investigated on individual reconstituted collagen type I fibers,
      ultraviolet radiation, and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC).
      Crosslinking with EDC for 4 hr yielded mechanical properties similar to the human
      ACL; therefore, scaffold crosslinking was done with EDC for 4 hr. A braid-twist
      scaffold design was used, and scaffolds were left uncrosslinked, crosslinked
      after the addition of gelatin, or crosslinked without gelatin. The ultimate
      tensile strength, Young's modulus, and viscoelastic properties of the scaffolds
      were then evaluated. In order to assess cellular response on the scaffolds,
      primary rat ligament fibroblast cells were seeded upon the scaffolds. Cell
      activity was evaluated at days 7, 14, and 21 using a Cell Titer 96((r)) AQueous
      One Solution Cell Proliferation Assay (MTS Assay). The mechanical testing results
      showed that among the three scaffold groups, the crosslinked scaffolds without
      gelatin displayed an ultimate tensile strength, Young's modulus, and viscoelastic
      properties that were closest to the human ACL. Improvements are still desired to
      enhance the mechanical compliance and ductility of these scaffolds. Cell activity
      was observed on all cell-seeded scaffolds by day 7, but by day 21 only the
      crosslinked scaffolds without gelatin displayed increased cellular activity
      compared with the negative controls. Although improvement is still needed, the
      results suggest that these scaffolds have the potential to contribute toward an
      ACL replacement strategy.

PMID- 22149932
TI  - Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs.
AB  - Much has been learned about how cells enter lymphoid tissues. But how do they
      leave? Sphingosine-1-phosphate (S1P) has emerged over the past decade as a
      central mediator of lymphocyte egress. In this review, we summarize the current
      understanding of how S1P promotes exit from the secondary lymphoid organs and
      thymus. We review what is known about additional requirements for emigration and
      summarize the mostly distinct requirements for exit from the bone marrow. Egress
      from lymphoid organs is limited during immune responses, and we examine how this
      regulation works. There is accumulating evidence for roles of S1P in directing
      immune cell behavior within lymphoid tissues. How such actions can fit together
      with the egress-promoting role of S1P is discussed. Finally, we examine current
      understanding of how FTY720, a drug that targets S1P receptors and is approved
      for the treatment of multiple sclerosis, causes immune suppression.

PMID- 22149934
TI  - The benefit of combination of oximes for the neuroprotective efficacy of
      antidotal treatment of sarin-poisoned rats.
AB  - The potency of the oxime HI-6 and two combinations of oximes (HI-6 + trimedoxime,
      HI-6 + K203) to reduce sarin-induced acute neurotoxic signs and symptoms was
      evaluated in this study. Sarin-induced neurotoxicity and the neuroprotective
      effects of atropine alone or in combination with HI-6 alone and HI-6 combined
      with trimedoxime or K203 in rats poisoned with sarin at a sublethal dose (108
      MUg/kg i.m.; 90% of LD(50) value) were monitored by a functional observatory
      battery (FOB) 24 h following sarin administration. The results indicate that both
      mixtures of oximes combined with atropine were able to survive sarin-poisoned
      rats 24 h following sarin administration while two non-treated sarin-poisoned
      rats and one sarin-poisoned rat treated with atropine alone or with atropine in
      combination with the oxime HI-6 died within 24 h following sarin poisoning. All
      types of antidotal treatment were able to decrease sarin-induced neurotoxic signs
      and symptoms but not completely. While atropine alone and atropine in combination
      with the oxime HI-6 were able to eliminate some sarin-induced neurotoxic signs
      and symptoms, the neuroprotective efficacy of both combinations of oximes with
      atropine was slightly higher. Thus, both tested combinations of oximes in
      combination with atropine bring a small benefit for the neuroprotective efficacy
      of antidotal treatment of acute sarin poisonings.

PMID- 22149933
TI  - Selection of self-reactive T cells in the thymus.
AB  - On the whole, the healthy adaptive immune system is responsive to foreign
      antigens and tolerant to self. However, many individual lymphocytes have, and
      even require, substantial self-reactivity for their particular functions in
      immunity. In this review, we discuss several populations of lymphocytes that are
      thought to experience agonist stimulation through the T cell receptor during
      selection: nTreg cells, iNKT cells, nIELs, and nTh17s. We discuss the nature of
      this self-reactivity, how it compares with conventional T cells, and why it is
      important for overall immune health. We also outline molecular pathways unique to
      each lineage and consider possible commonalities to their development and
      survival.

PMID- 22149935
TI  - General versus central adiposity and relationship to pediatric metabolic risk.
AB  - BACKGROUND: The influence of moderate-to-vigorous physical activity (MVPA) and
      general versus central adiposity on pediatric metabolic risk is not well
      described. METHODS: Secondary analyses on pediatric participants from the
      National Health and Nutrition Examination Survey, 2003-2006 (n=2,155). MVPA
      (min/day) and adherence to MVPA recommendations were assessed objectively by
      accelerometers. Body mass index (BMI) z-score and waist circumference (WC) were
      measured by standard protocols. The main dependent variables included an overall
      metabolic risk score and clinical tests related to metabolic risk. A series of
      linear regression analyses were used to examine BMI z-score versus WC as a
      mediator of the relationship between MVPA and the metabolic risk score or the
      individual components, controlling for sociodemographic covariates. All analyses
      with BMI z-score as an independent variable controlled for WC and vice versa. The
      product-of-coefficients method was used to test for mediation. RESULTS: MVPA
      adherence was inversely associated and WC was positively associated with the
      metabolic risk score (all P<0.05). MVPA was inversely associated with systolic
      blood pressure and positively associated with high-density lipoprotein
      cholesterol (HDL-C) (all P<0.05). WC was inversely associated with HDL-C and
      positively associated with C-reactive protein (CRP), glycohemoglobin, fasting
      triglycerides, and fasting insulin (all P<0.05). WC mediated the relationship
      between MVPA and CRP or HDL-C (both P<0.05). CONCLUSIONS: MVPA correlated with
      pediatric metabolic risk and this relationship was mediated by central adiposity
      for CRP and HDL-C. This finding suggests the need for programs to screen for and
      improve children's MVPA and WC.

PMID- 22149936
TI  - Length of stay benchmarks for inpatient rehabilitation after stroke.
AB  - PURPOSE: In Canada, no standardized benchmarks for length of stay (LOS) have been
      established for post-stroke inpatient rehabilitation. This paper describes the
      development of a severity specific median length of stay benchmarking strategy,
      assessment of its impact after one year of implementation in a Canadian
      rehabilitation hospital, and establishment of updated benchmarks that may be
      useful for comparison with other facilities across Canada. METHOD: Patient data
      were retrospectively assessed for all patients admitted to a single post-acute
      stroke rehabilitation unit in Ontario, Canada between April 2005 and March 2008.
      Rehabilitation Patient Groups (RPGs) were used to establish stratified median
      length of stay benchmarks for each group that were incorporated into team rounds
      beginning in October 2009. Benchmark impact was assessed using mean LOS, FIM((r))
      gain, and discharge destination for each RPG group, collected prospectively for
      one year, compared against similar information from the previous calendar year.
      Benchmarks were then adjusted accordingly for future use. RESULTS: Between
      October 2009 and September 2010, a significant reduction in average LOS was noted
      compared to the previous year (35.3 vs. 41.2 days; p < 0.05). Reductions in LOS
      were noted in each RPG group including statistically significant reductions in 4
      of the 7 groups. As intended, reductions in LOS were achieved with no significant
      reduction in mean FIM((r)) gain or proportion of patients discharged home
      compared to the previous year. Adjusted benchmarks for LOS ranged from 13 to 48
      days depending on the RPG group. CONCLUSIONS: After a single year of
      implementation, severity specific benchmarks helped the rehabilitation team
      reduce LOS while maintaining the same levels of functional gain and achieving the
      same rate of discharge to the community.

PMID- 22149937
TI  - Hospitalists at an academic medical center, part 1: impact of a voluntary pilot
      hospitalist program.
AB  - The use of hospitalists-physicians who limit their practice largely or
      exclusively to hospital inpatient care-has been a growing trend in the United
      States. The authors examine some pressures affecting an academic medical center
      and present the results of a hospitalist pilot project there. Based on the
      criteria of reduced patient length of hospital stay, hospital financial savings,
      physician satisfaction, and payer interest, the pilot hospitalist program was
      successful within 6 months.

PMID- 22149938
TI  - Hospitalists at an academic medical center, part 2: guidelines and suggestions
      for the successful expansion of a voluntary pilot hospitalist program.
AB  - Previously, the authors discussed the successful introduction of a pilot
      hospitalist program at an academic medical center. Here they examine best
      practices for the expansion of such a program. Many studies have shown
      hospitalists to be associated with improvements in hospital quality indicators
      such as decreased length of stay, but the conditions necessary for the expansion
      of a hospitalist program have received considerably less attention. The authors
      review guidelines and empirical evidence from the literature for the successful
      implementation of hospitalist programs generally and present specific
      recommendations for a previously described pilot hospitalist program at an
      academic medical center.

PMID- 22149939
TI  - Accountable care organization musical chairs: will there be a seat remaining for
      the small group or solo practice? [corrected].
AB  - When it was introduced in the Affordable Care Act of 2010 as the new 2012 payment
      model for Medicare, an accountable care organization (ACO) was a new and untested
      concept in healthcare delivery and payment. The authors estimated the likelihood
      of engagement in ACOs by small group and solo healthcare practitioners. An
      evaluation of five case studies showed that significant organizational,
      financial, and technological challenges had to be met in order to launch an ACO.
      Sufficient resources to meet those challenges were best supplied by large
      organizations. Small or solo practices participated only through varying levels
      of integration as salaried physicians or in independent practice associations or
      physician hospital organizations.

PMID- 22149941
TI  - Synergistic effect of medium, matrix, and exogenous factors on the adhesion and
      growth of human pluripotent stem cells under defined, xeno-free conditions.
AB  - Human pluripotent stem cells (hPSCs), including human embryonic stem cells
      (hESCs) and human induced pluripotent stem cells (hiPSCs), share the properties
      of unlimited self-renewal and the capacity to become any cell type in the body,
      making them well suited for regenerative medicine and cell therapy. So far,
      almost all hPSC lines have been directly or indirectly exposed to animal-derived
      products, which would hinder their use for clinical purposes. One of the biggest
      challenges in this area is to remove animal components from the derivation,
      propagation, and cryopreservation of hPSCs. Moreover, the presence of undefined
      components of animal or human origin in culture system may interfere with the
      interpretation of the effect of exogenous agents on the growth and
      differentiation of hPSCs and are prone to significant variability. To explore
      hPSC expansion in defined, xeno-free conditions, 2 different groups of culture
      systems were used to culture different hESC and hiPSC lines. Our results
      suggested that (1) medium, matrix, and exogenous factors have synergistic effects
      on the adhesion and growth of hPSCs; (2) cooperation of exogenous factors
      including basic fibroblast growth factor, Rho-associated kinase inhibitor (ROCK),
      and other growth factors is critical for hPSC adhesion and proliferation; (3)
      basal media have different effects on hPSC attachment to the culture surface; and
      (4) a medium or matrix component can work synergistically in one culture system,
      and not at all in another. In this study, we found that Vitronectin/TeSR2 and
      PDL/HEScGRO (Y-27632) systems were optimal for maintaining the long-term culture
      of 3 hESC lines and 2 hiPSC lines under defined, xeno-free conditions.

PMID- 22149942
TI  - A new feruloyl amide derivative from the fruits of Tribulus terrestris.
AB  - A new feruloyl amide derivative, named tribulusamide C, was isolated from the
      fruits of Tribulus terrestris. Its structure was determined on the basis of
      spectroscopic analysis including IR, 1-D-, 2-D-NMR and HR-ESI-MS. The structure
      of tribulusamide C was characterised by a unit of pyrrolidine-2,5-dione, which
      distinguished it from other lignanamides previously isolated from the fruits of
      T. terrestris.

PMID- 22149943
TI  - Nonpolypoid colorectal neoplasms: gender differences in prevalence and malignant
      potential.
AB  - OBJECTIVE: Colonoscopy may fail to prevent colorectal cancer, especially in the
      proximal colon and in women. Nonpolypoid colorectal neoplasms may potentially
      explain some of these post-colonoscopy cancers. In the present study, we aimed to
      examine the prevalence and malignant potential of nonpolypoid colorectal
      neoplasms in a large population, with special attention to gender and location.
      METHODS: We performed a cross-sectional study of all consecutive patients
      undergoing elective colonoscopy at a single academic medical center. The
      endoscopists were familiarized on the detection and treatment of nonpolypoid
      lesions. Advanced histology was defined by the presence of high-grade dysplasia
      or early cancer. RESULTS: We included 2310 patients (53.9% women, mean age 58.4
      years) with 2143 colorectal polyps. Prevalences of colorectal neoplasms and
      nonpolypoid colorectal neoplasms were lower in women than in men (20.9% vs.
      33.7%, p < 0.001 and 3.0% vs. 5.5%, p = 0.002). In women, nonpolypoid colorectal
      neoplasms were significantly more likely to contain advanced histology than
      polypoid ones (OR 2.89, 95% CI 1.24-6.74, p = 0.01), while this was not the case
      in men (OR 0.91, 95% CI 0.40-2.06, p = 0.83). Proximal neoplasms with advanced
      histology were more likely to be nonpolypoid than distal ones (OR 4.68, 95% CI
      1.54-14.2, p = 0.006). CONCLUSION: Nonpolypoid mechanisms may play an important
      role in colorectal carcinogenesis, in both women and men. Although women have
      fewer colorectal neoplasms than men, they have nonpolypoid colorectal neoplasms,
      which frequently contain advanced histology.

PMID- 22149944
TI  - Photoinduced switching of the current through a single molecule: effects of
      surface plasmon excitations of the leads.
AB  - The photoinduced switch of the current through a single molecule is studied
      theoretically by including plasmon excitations of the leads. A molecule weakly
      linked to two spherical nanoelectrodes is considered resulting in sequential
      charge transmission scheme. Taking the molecular charging energy (relative to the
      equilibrium lead chemical potential) to be comparable to the molecular excitation
      energy, an efficient current switch in a low voltage range becomes possible. A
      remarkable enhancement of the current is achieved due to simultaneous plasmon
      excitations in the electrodes. The behavior is explained by an increased
      molecular absorbance due to oscillator strength transfer from the electrode
      plasmon excitations and by a net excitation energy motion from the electrodes to
      the molecule.

PMID- 22149945
TI  - Curcumin-containing chitosan nanoparticles as a potential mucoadhesive delivery
      system to the colon.
AB  - In the present study, we investigate the mucoadhesive characteristics and release
      of the anticancer agent curcumin, contained in chitosan nanoparticles (CS-NPs).
      Such a system has potential therapeutic benefits in the treatment of colon cancer
      through prolonged retention and delivery. The CS-NPs were ionically gelled with
      tripolyphosphate (TPP) and registered an isoelectric pH of 6.2 (z-average
      diameter of 214 nm +/- 1.0 nm). pH variations around the isoelectric point caused
      a reduction in CS-NPs electrical charge which correspondingly increased the z
      average due to agglomeration. Curcumin release from CS-NPs was slowest at
      chitosan to TPP weight ratio of 3:1, with a significant retention (36%) at the
      end of 6 h. Adsorption isotherms of mucin on CS-NPs fitted both the Freundlich
      and Langmuir models, suggesting a monolayer-limited adsorption on heterogeneous
      sites with varied affinities. Encapsulated curcumin exerted an influence on the
      adsorption of mucin due to H-bonding as well as pi-pi interactions between the
      phenolic moieties of curcumin and mucin.

PMID- 22149955
TI  - Heavy episodic drinking among dating partners: a longitudinal actor-partner
      interdependence model.
AB  - Heavy episodic drinking (HED) is a major health problem for young adults. Rates
      of HED have remained consistently high among young adults for the past two
      decades. Though research has identified various intrapersonal, interpersonal, and
      environmental contributors to HED, the majority of research focuses on
      intrapersonal factors. As such, more research is needed to test the role that
      specific interpersonal relationships play in perpetuating HED. This study tests
      the partner influence hypothesis that suggests partners in romantic relationships
      influence one another's HED over time. A sample of 208 young, nonmarried,
      heterosexual dating couples completed HED measures at baseline and again 28 days
      later. Actor-partner interdependence modeling revealed significant actor effects,
      demonstrating stability in HED within each partner over time. Results also showed
      significant partner effects where HED in both young men and women in dating
      relationships positively influenced their partners' future HED over a relatively
      short time frame. Patterns in the results suggest both women and men are more
      affected by their own than by their partner's prior level of HED. Nonetheless,
      small partner effects were present for both women and men. Results support the
      partner influence hypothesis and suggest HED is a self-propagating behavior
      sustained, in part, by a pattern of interpersonal influence. These results
      highlight the importance of considering both intrapersonal and interpersonal
      factors when implementing prevention and intervention programs for young adults'
      HED.

PMID- 22149956
TI  - Reasons for substance use among people with psychotic disorders: method
      triangulation approach.
AB  - Substance use disorders (SUD) are common among people with psychotic disorders
      and are associated with many negative consequences. Understanding the reasons for
      substance use in this population may allow for the development of more effective
      prevention and intervention strategies. We examined reasons for tobacco, alcohol,
      or cannabis use among people with psychotic disorders. Sixty-four participants
      with a diagnosed psychotic disorder completed a self-report reasons for use
      questionnaire. A subset of eight participants completed semi-structured
      qualitative interviews. Both the qualitative and quantitative data indicated that
      reasons for use of tobacco, alcohol, and cannabis differed considerably. Tobacco
      was primarily used for coping motives, alcohol for social motives, and cannabis
      for pleasure enhancement motives. Prevention and intervention strategies
      targeting coexisting psychotic disorders and SUD may improve in effectiveness if
      they address the perceived beneficial effects of tobacco use, the strong social
      pressures influencing alcohol use and if they encourage cannabis users to seek
      alternative pleasurable activities.

PMID- 22149957
TI  - Low-dose total-body gamma irradiation modulates immune response to acute proton
      radiation.
AB  - Health risks due to exposure to low-dose/low-dose-rate radiation alone or when
      combined with acute irradiation are not yet clearly defined. This study
      quantified the effects of protracted exposure to low-dose/low-dose-rate gamma
      rays with and without acute exposure to protons on the response of immune and
      other cell populations. C57BL/6 mice were irradiated with 57Co (0.05 Gy at 0.025
      cGy/h); subsets were subsequently exposed to high-dose/high-dose-rate proton
      radiation (250 MeV; 2 or 3 Gy at 0.5 Gy/min). Analyses were performed at 4 and 17
      days postexposure. Spleen and thymus masses relative to body mass were decreased
      on day 4 after proton irradiation with or without pre-exposure to gamma rays; by
      day 17, however, the decrease was attenuated by the priming dose. Proton dose
      dependent decreases, either with or without pre-exposure to gamma rays, occurred
      in white blood cell, lymphocyte and granulocyte counts in blood but not in
      spleen. A similar pattern was found for lymphocyte subpopulations, including CD3+
      T, CD19+ B, CD4+ T, CD8+ T and NK1.1+ natural killer (NK) cells. Spontaneous DNA
      synthesis by leukocytes after proton irradiation was high in blood on day 4 and
      high in spleen on day 17; priming with gamma radiation attenuated the effect of 3
      Gy in both body compartments. Some differences were also noted among groups in
      erythrocyte and thrombocyte characteristics. Analysis of splenocytes activated
      with anti-CD3/anti-CD28 antibodies showed changes in T-helper 1 (Th1) and Th2
      cytokines. Overall, the data demonstrate that pre-exposure of an intact mammal to
      low-dose/low-dose-rate gamma rays can attenuate the response to acute exposure to
      proton radiation with respect to at least some cell populations.

PMID- 22149958
TI  - Radiation dose associated with renal failure mortality: a potential pathway to
      partially explain increased cardiovascular disease mortality observed after whole
      body irradiation.
AB  - Whole-body and thoracic ionizing radiation exposure are associated with increased
      cardiovascular disease (CVD) risk. In atomic bomb survivors, radiation dose is
      also associated with increased hypertension incidence, suggesting that radiation
      dose may be associated with chronic renal failure (CRF), thus explaining part of
      the mechanism for increased CVD. Multivariate Poisson regression was used to
      evaluate the association of radiation dose with various definitions of chronic
      kidney disease (CKD) mortality in the Life Span Study (LSS) of atomic bomb
      survivors. A secondary analysis was performed using a subsample for whom self
      reported information on hypertension and diabetes, the two biggest risk factors
      for CRF, had been collected. We found a significant association between radiation
      dose and only our broadest definition of CRF among the full cohort. A quadratic
      dose excess relative risk model [ERR/Gy(2) = 0.091 (95% CI: 0.05, 0.198)] fit
      minimally better than a linear model. Within the subsample, association was also
      observed only with the broadest CRF definition [ERR/Gy(2) = 0.15 (95% CI: 0.02,
      0.32)]. Adjustment for hypertension and diabetes improved model fit but did not
      substantially change the ERR/Gy(2) estimate, which was 0.17 (95% CI: 0.04, 0.35).
      We found a significant quadratic dose relationship between radiation dose and
      possible chronic renal disease mortality that is similar in shape to that
      observed between radiation and incidence of hypertension in this population. Our
      results suggest that renal dysfunction could be part of the mechanism causing
      increased CVD risk after whole-body irradiation, a hypothesis that deserves
      further study.

PMID- 22149960
TI  - Merry christmas for patients with hemophilia B.

PMID- 22149959
TI  - Adenovirus-associated virus vector-mediated gene transfer in hemophilia B.
AB  - BACKGROUND: Hemophilia B, an X-linked disorder, is ideally suited for gene
      therapy. We investigated the use of a new gene therapy in patients with the
      disorder. METHODS: We infused a single dose of a serotype-8-pseudotyped, self
      complementary adenovirus-associated virus (AAV) vector expressing a codon
      optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral
      vein in six patients with severe hemophilia B (FIX activity, <1% of normal
      values). Study participants were enrolled sequentially in one of three cohorts
      (given a high, intermediate, or low dose of vector), with two participants in
      each group. Vector was administered without immunosuppressive therapy, and
      participants were followed for 6 to 16 months. RESULTS: AAV-mediated expression
      of FIX at 2 to 11% of normal levels was observed in all participants. Four of the
      six discontinued FIX prophylaxis and remained free of spontaneous hemorrhage; in
      the other two, the interval between prophylactic injections was increased. Of the
      two participants who received the high dose of vector, one had a transient,
      asymptomatic elevation of serum aminotransferase levels, which was associated
      with the detection of AAV8-capsid-specific T cells in the peripheral blood; the
      other had a slight increase in liver-enzyme levels, the cause of which was less
      clear. Each of these two participants received a short course of glucocorticoid
      therapy, which rapidly normalized aminotransferase levels and maintained FIX
      levels in the range of 3 to 11% of normal values. CONCLUSIONS: Peripheral-vein
      infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels
      sufficient to improve the bleeding phenotype, with few side effects. Although
      immune-mediated clearance of AAV-transduced hepatocytes remains a concern, this
      process may be controlled with a short course of glucocorticoids without loss of
      transgene expression. (Funded by the Medical Research Council and others;
      ClinicalTrials.gov number, NCT00979238.).

PMID- 22149961
TI  - Dietary whole glucan particles do not affect antibody or cell-mediated immune
      responses to influenza virus vaccination in mice.
AB  - Influenza virus is a serious health concern. beta-glucans derived from plants,
      bacteria, and fungi have been shown to potentiate immune system responses
      including those elicited by vaccination. However, in these studies beta-glucan
      was administered as an adjuvant in the vaccine preparation. We hypothesized that
      addition of a commercially available whole glucan particle supplement to the diet
      would improve immune response to primary and secondary influenza vaccination in
      mice. beta-glucan was added to pelleted diet and fed to mice at concentrations
      designed to deliver 0 (control), 1.8 or 90 mg.kg(-1).day(-1) to each mouse.
      Influenza vaccine was given intramuscularly in the left hindlimb and primary and
      secondary responses were assessed. Supplementation with beta-glucan was not
      effective in boosting immune responses to the vaccine, either in the primary or
      secondary vaccination experiments. Surprisingly, addition of particulate beta
      glucan to the vaccine itself also failed to elicit a greater antibody response.
      These observations suggest that this particular form of beta-glucan is
      ineffective in boosting immune response to intramuscular influenza vaccination.
      Further study is warranted to determine if the use of different mouse models,
      different vaccine delivery systems, or beta-glucans purified from different
      strains of bacteria, fungi, or plants could improve outcomes using this or
      similar protocols.

PMID- 22149963
TI  - Sexual behavior and high-risk human papillomavirus in 15- to 22-year-old
      Lithuanian women.
AB  - We determined the risk of high-risk human papillomavirus (HR-HPV) infection in
      169 15- to 22-year-old sexually active Lithuanian women attending two outpatient
      clinics in Vilnius. The Digene((r)) Hybrid Capture II DNA test was used to test
      for HR-HPV infection on material collected by cervical swabs. The findings were
      compared with the pattern of sexual behavior as given in questionnaire replies.
      The overall risk of HR-HPV was 23.1%, but 60.0% in adolescents <=15 years old.
      Mean age at first intercourse was 17.1 years; 73.5% of women had only had one
      sexual partner and 24.5% more than one. The risk of HR-HPV was higher in women
      with more than one sexual partner, and related to being a smoker and to early age
      at the first intercourse. Our results confirm that smoking, early coitarche,
      multiple sexual partners and unprotected vaginal intercourse are related to the
      risk of HR-HPV infection in young women.

PMID- 22149964
TI  - Sonic hedgehog enhances the proliferation and osteogenic differentiation of bone
      marrow-derived mesenchymal stem cells.
AB  - MSCs (mesenchymal stem cells) may be promising seed cells for tissue regeneration
      because of their self-renewal and multi-differentiation potential. Shh (sonic
      hedgehog) is involved in the skeletal formation during embryo development and
      skeletal regeneration. However, how Shh regulates the biological characteristics
      of BM-MSCs (bone marrow-derived MSCs) is poorly understood. We have investigated
      the effect of rShh-N (recombinant N-terminal Shh) on the proliferation and
      osteogenic differentiation of rBM-MSCs (rat BM-MSCs) in vitro. rBM-MSCs were
      treated with rShh-N at concentrations up to 200 ng/ml. Proliferation and colony
      forming ability of rBM-MSCs were increased in a dose-dependent manner. rShh-N
      increased the ratio of cells in S and G2/M phase, as well as the number of Ki-67+
      cells. In addition, ALP (alkaline phosphatase) activity and matrix mineralization
      were enhanced by 200 ng/ml rShh-N. Real-time PCR showed that rShh-N (200 ng/ml)
      up-regulated the expression of genes encoding Cbfa-1 (core-binding factor
      alpha1), osteocalcin, ALP and collagen type I in rBM-MSCs. This information
      reveals some potential of rShh-N in the therapeutics of bone-related diseases.

PMID- 22149966
TI  - A modified RBL-2H3 mediator release assay for the detection of polyclonal IgE
      antibody.
AB  - RBL-2H3 mediator release assay, developed for specific IgE screening studies, was
      not as sensitive as passive cutaneous anaphylaxis (PCA) assay in the polyclonal
      antibody detection. In the present investigation, the detection sensitivity of
      RBL-2H3 assay was elevated by modifying the experiment protocols from choosing
      the proper releasing medium and optimizing the sensitization manner. The
      polyclonal antibody was generated from Brown Norway (BN) rats exposed to
      Ovalbumin (OVA). In contrast to Tyrode buffer A, RBL-2H3 cells cultured in DMEM
      had a lower spontaneous secretion and a higher response to antigen stimulation,
      both of which could help to increase the detection sensitivity. The rat sera used
      in the sensitization process should be diluted appropriately to avoid the
      proliferation-promoting effect on RBL-2H3 cells. The results of the kinetics of
      sensitization showed that prolonging the sensitization time and then reculturing
      the cells in IgE free medium for a further 24 h after the removal of rat sera
      could reach a marked increase in the degree of sensitization. The highest anti
      OVA antibody titer detected by the modified RBL-2H3 assay was 4096, while PCA
      assay was 1024. These data provide evidence that the modified RBL-2H3 mediator
      release assay has a promising prospect in the determination of the biologic
      activity of polyclonal antibody.

PMID- 22149965
TI  - Characterization of tissue-specific and developmentally regulated alternative
      splicing of exon 64 in the COL5A1 gene.
AB  - The COL5A1 gene, a member of the clade B fibrillar collagen gene family, was
      recently shown to contain two alternatively spliced exons (64A and 64B) that
      encode 23 amino acids in the carboxyl-terminal propeptide. The two are identical
      in length, very similar in sequence, and used in a mutually exclusive fashion
      because of the small intron that separates them. Each COL5A1 allele uses both
      exons, but a given transcript will contain only one of the two exons. The
      sequences in other species are highly conserved at the amino acid level. The
      expression profile of the two isoforms was determined from analysis of RNA levels
      in a panel of murine tissues. While both isoforms were found in all tissues
      studied, actively proliferating tissues (liver, lung) used isoform B more often,
      while a less mitotically active tissue, brain, had a higher proportion of exon
      64A. The high degree of conservation between the two exons is consistent with a
      regional genomic duplication. The presence of the two isoforms as far back as
      pufferfish (tetraodon) implies an important functional significance. The exact
      role determined by the two sequences is not known, but involvement in the
      determination of chain composition of mature type V collagen or regulation of
      cell activity is possible, given the differences in tissue distribution.

PMID- 22149967
TI  - The use of antipsychotics in a medium-long stay psychiatric hospital from 1998 to
      2010.
AB  - OBJECTIVE: Atypical agents have emerged as the dominant choice among
      antipsychotics. Data about development of antipsychotic use in medium-long stay
      psychiatric hospitals is lacking. MATERIAL AND METHODS: Antipsychotic drug
      consumption data and cost was obtained from 1998 to 2010 for all inpatients of a
      231-bed psychiatric hospital. Number of hospital stays was obtained from the
      hospital admission unit. Daily defined dose (DDD) values were those assigned by
      the WHO. Antipsychotic use was also measured using recently available consensus
      based recommendations. Antipsychotic use was then calculated as the sum of
      individual DDD or total equivalent doses of all antipsychotics divided by the
      annual stay number. RESULTS: Antipsychotic use increased 135% from 1998 to 2010
      when measured in DDDs or 108% when measured with the consensus-based
      recommendations. Antipsychotic expenditure has risen six-fold since 1998. This
      augmentation is due to the increase of use of atypical antipsychotics.
      CONCLUSION: In conclusion, antipsychotic use has at least doubled in the last 13
      years. This growth, attributable to an increase in atypical drug use, has
      contributed to a six-fold increase in the total antipsychotic expenditure.
      Whether this prescription pattern has translated into palpable clinical benefits
      remains unclear.

PMID- 22149968
TI  - Coating glass-ionomer cements with a nanofilled resin.
AB  - OBJECTIVES: The objective of this study was to investigate the effect of a
      nanofilled resin coat on the flexural strength (FS) and the early wear (after
      50,000 and 200,000 cycles) of the glass-ionomer cements Fuji IX GP Extra (FIXE)
      and Ketac Molar Aplicap (KM). MATERIALS AND METHODS: Specimens were prepared and
      half of them were coated with G-Coat plus. The uncoated specimens were used as
      controls. Flexural strength (n = 10) was evaluated after 24 h using a 3-point
      bending test on a universal testing machine (ISO 9917-2). Wear (n = 20) was
      evaluated after 50,000 and 200,000 cycles using the ACTA wear machine. One-way,
      two-way ANOVA and Tukey post-hoc tests were used to analyze differences in FS and
      wear. RESULTS: For FIXE the coat significantly increased the FS and the wear
      along the two time spans. KM did not show a significant difference in FS with the
      coat. Improvements in wear were observed only after 50,000 cycles. CONCLUSION:
      Based on these laboratory results, it is concluded that G-coat Plus is indicated
      in association with GP IX Extra with the aim to improve the mechanical properties
      of the former. However, this study is limited to a short-term observation.

PMID- 22149969
TI  - An evolving web of signaling networks regulated by Cripto-1.
AB  - Over the past few decades, our understanding of the embryonic gene Cripto-1 has
      considerably advanced through biochemical, cell biology, and animal studies.
      Cripto-1 performs key functions during embryonic development, while it
      dramatically disappears in adult tissues, except possibly in adult tissue stem
      cells. Cripto-1 is re-expressed in human tumors promoting cell proliferation,
      migration, invasion, epithelial to mesenchymal transition, and tumor
      angiogenesis. This diversity of biological effects is dependent upon interaction
      of Cripto-1 with an extensive array of signaling molecules. In fact, Cripto-1
      modulates signaling of transforming growth factor-beta family members, including
      Nodal, GDF-1/-3, Activin, and TGF-beta1, activates c-src/MAPK/Protein Kinase B
      (AKT) pathway in a Glypican-1 and GRP78-dependent manner, and cross-talks with
      erbB4, Wnt/beta-catenin, Notch, Caveolin-1, and Apelin/putative receptor protein
      related to Angiotensin-type I receptor (APJ) pathways. This article provides an
      updated survey of the various signaling pathways modulated by Cripto-1 with a
      focus on mechanistic insights in our understanding of the biological function of
      Cripto-1 in eukaryotic cells.

PMID- 22149970
TI  - Viral infections: impact on chemokines and chemokine receptors.

PMID- 22149971
TI  - Binding antibody responses to the immunogenic regions of viral envelope in HIV-1
      infected Indian children.
AB  - Limited information exists on the antibody responses elicited against the viral
      envelope in HIV-1-infected children. In this cross-sectional study, we assessed
      the antibody responses against three different immunogenic regions of HIV-1
      envelope, namely V3 region of gp120, membrane proximal external region (MPER),
      and immunodominant loop (IDL) of gp41 in HIV-1-infected children from north
      India. We recruited 75 HIV-1-infected (40 antiretroviral naive and 35 treated)
      children, with age ranging from 1.5 to 16 y. Antibodies to V3 and the IDL region
      were found in a majority of the infected children, whereas antibodies to MPER
      were found in approximately one-third of the children studied. Higher antibody
      titers to the immunogenic regions corresponded to the symptomatic stages of HIV-1
      infection in both naive and antiretroviral therapy (ART)-treated children. High
      titers of anti-V3C and anti-IDL antibodies were observed in a subset of
      antiretroviral-naive patients with suppressed viremia (<47 RNA copies/mL),
      suggesting that antibodies to these immunogenic regions are present regardless of
      their viremic status. Further, the antibody titers were significantly lower in
      the plasma of treated patients compared to naive patients, regardless of whether
      they were virologically suppressed or not. This is the first report on the
      antibody responses elicited in HIV-1-infected children in India. The study may
      help to understand the humoral antibody responses directed against viral envelope
      in HIV-1-infected children.

PMID- 22149972
TI  - A case of bronchial aspergillosis caused by Aspergillus udagawae and its
      mycological features.
AB  - Aspergillus udagawae and A. fumigatus share similar morphological features but
      they differ genetically. There is also an important clinical distinction as A.
      udagawae is less sensitive to amphotericin B than A. fumigatus. We encountered a
      rare case of bronchial infection due to A. udagawae that was successfully treated
      with voriconazole. An 82-year-old woman with diabetes mellitus complained of
      bloody sputum. Bronchoscopy revealed a white plugged region at the origin of the
      right bronchi B5. Cytological study revealed a clot composed of filamentous fungi
      and Aspergillus spp. was detected by culture. Molecular analysis revealed that
      the causative agent was A. udagawae, and voriconazole was used for the treatment.
      In comparison to A. fumigatus, the A. udagawae strain isolated in this case was
      less sensitive to amphotericin B, less virulent in immunosuppressed mice, and
      more sensitive to hydrogen peroxide, features that are almost identical to those
      of the previously reported isolates of the fungus. We should be aware of the
      emergence of new Aspergillus species that might pose a clinical threat.

PMID- 22149973
TI  - Fungaemia caused by Candida pulcherrima.
AB  - Although neonatal bloodstream infections may be caused by a variety of fungi,
      invasive fungaemia due to Candida pulcherrima in a premature neonate has not been
      previously reported. We describe such a case in which antifungal susceptibility
      test data led to successful therapy. A colonized catheter used for parenteral
      nutrition is presumed to have been the main source of this persistent infection.

PMID- 22149974
TI  - Positional identity of murine mesenchymal stem cells resident in different organs
      is determined in the postsegmentation mesoderm.
AB  - Although mesenchymal stem cells (MSCs) of distinct tissue origin have a large
      number of similarities and differences, it has not been determined so far whether
      tissue-resident MSCs are the progenies of one ancestor cell lineage or the
      results of parallel cell developmental events. Here we compared the expression
      levels of 177 genes in murine MSCs derived from adult and juvenile bone marrow
      and adult adipose tissue, as well as juvenile spleen, thymus, and aorta wall by
      quantitative real-time polymerase chain reaction and the results were partially
      validated at protein level. All MSC lines uniformly expressed a large set of
      genes including well-known mesenchymal markers, such as alpha-smooth muscle
      actin, collagen type I alpha-chain, GATA6, Mohawk, and vimentin. In contrast,
      pluripotency genes and the early mesodermal marker T-gene were not expressed. On
      the other hand, different MSC lines consistently expressed distinct patterns of
      Hox genes determining the positional identity of a given cell population.
      Moreover, MSCs of different origin expressed a few other transcription factors
      also reflecting their topological identity and so the body segment or organ to
      which they normally contributed in vivo: (1) thymus-derived cells specifically
      expressed Tbx5 and Pitx2; (2) spleen-derived MSCs were characterized with Tlx1
      and Nkx2.5; (3) Pitx1 designated femoral bone marrow cells and (4) En2 appeared
      in aorta wall-derived MSCs. Thus, MSCs exhibited topographic identity and memory
      even after long-term cultivation in vitro. On the basis of these results, we
      suggest that postnatal MSCs isolated from different anatomical sites descend from
      precursor cells developing in the postsegmentation mesoderm.

PMID- 22149975
TI  - Low achieved diastolic pressure in tightly controlled mid-older hypertensive
      subjects is associated with favorable arterial properties.
AB  - Low diastolic blood pressure (DBP) is commonly seen in well-controlled
      hypertensive subjects. We evaluated arterial properties in 53 hypertensive
      subjects with low on-treatment DBP (<70 mm Hg; LODP), 54 subjects with normal BP
      and spontaneously low DBP (SLDP), and 52 treated hypertensive subjects with DBP
      >=70 mm Hg (HNDP). The two measures of large artery rigidity, pulse wave velocity
      and augmentation index, were similar in LODP and SLDP groups. In contrast, the
      HNDP group had higher PWV and the lowest large and small artery compliance in
      comparison with all other groups. Low on-treatment DBP is associated with
      favorable arterial properties in mid-older hypertensive patients.

PMID- 22149976
TI  - Vegetational variation of phenolic compounds in Epilobium angustifolium.
AB  - Epilobium angustifolium L. herbs are used in ethnomedicine to treat benign
      prostate hyperplasia. The aim of the study was to investigate the phenolic
      contents in distinct E. angustifolium organs during the whole vegetational period
      from May to October. The plants were obtained from a remote habitat in Estonia
      and spectrophotometrically analysed for the total polyphenol, tannin, and
      flavonoid contents. The total polyphenol content was the highest in roots (85 mg
      g(-1)) and stems (67 mg g(-1)) in July. The total flavonoid content was the
      highest in leaves (2.36 mg g(-1)) and flowers (2.09 mg g(-1)) and it remained
      relatively stable during the summer months. The highest tannin content was found
      in small growing plants in May; in older ones it declined, whereas the absolute
      yield per plant was greater. In sum, the aerial organs without stems collected in
      July-August are the best choice to get E. angustifolium plant material with
      stable high phenolic content.

PMID- 22149977
TI  - Adalimumab in budesonide and methotrexate refractory collagenous colitis.
AB  - BACKGROUND: We described three patients with collagenous colitis (CC) who
      developed side effects or were refractory to both budesonide and methotrexate and
      were given adalimumab (ADA) as a third-line treatment. METHOD/PATIENTS: Three
      patients (two women, mean age 45 years and one man, 74 years old) were included.
      Mean bowel movements per day per week were calculated and stool weight/24 h
      registered prior to and following ADA treatment. ADA was given in doses 160 mg
      s.c. (baseline), 80 mg (week 2) and 40 mg (week 4). Sigmoidoscopies with biopsies
      were performed at baseline and after 6 weeks to examine changes in histology. The
      Psychological General Well-Being Index (PGWBI) and Short Health Scale (SHS) were
      used at baseline and after 6 weeks. RESULTS: The two female patients tolerated
      the treatment well. The male patient developed, despite clinical response, side
      effects (vomiting, abdominal pain) after 80 mg of ADA and the treatment was
      stopped as side effects reoccurred after rechallenge. The two women were in
      clinical remission at week 6 and the mean stool frequency per day decreased from
      mean 11 to 2. Mean stool weight/24 h changed from 600 to 185 g. The quality of
      life improved drastically in all patients. There were no consistent changes in
      histology. CONCLUSION: ADA seems effective in budesonide and methotrexate
      refractory CC and can be administrated to selected patients to achieve clinical
      remission, improve quality of life and possibly avoid colectomy. Further studies
      for induction and maintenance treatment should be conducted to confirm efficacy
      and examine safety issues, even in long term.

PMID- 22149989
TI  - Aicardi-Goutieres syndrome: from patients to genes and beyond.
AB  - Aicardi-Goutieres syndrome (AGS) is a hereditary neurodegenerative disorder
      characterized mainly by early onset progressive encephalopathy, concomitant with
      an increase in interferon-alpha levels in the cerebrospinal fluid. Although it
      was initially mistaken for intrauterine viral infections, AGS has now been
      genetically attributed to a lack of adequate processing of cellular nucleic acid
      debris, which culminates in the perpetual trigger of the innate and acquired
      immune responses. Although the exact mechanisms governing AGS are not fully
      understood, significant strides have been recently achieved in better
      characterizing the disorder and the molecular functions of the five known
      proteins found mutated in AGS. Studies have now uncovered that AGS is tightly
      linked with the predisposition to other autoimmune disorders such as familial
      chilblain lupus and systemic lupus erythematosus. Moreover, at least two of the
      proteins mutated in AGS, namely TREX1 and SAMHD1, also seem to have antagonistic
      roles in safeguarding humans from human immunodeficiency virus (HIV) infections.
      We hereby synthesize the current developments into the greater framework of AGS
      and suggest that a better understanding of AGS might help usher a better
      treatment not only for some autoimmune disorders but also possibly for patients
      suffering from HIV infections, too.

PMID- 22149990
TI  - Ultrafast supercontinuum spectroscopy of carrier multiplication and biexcitonic
      effects in excited states of PbS quantum dots.
AB  - We examine the population dynamics of multiple excitons in PbS quantum dots using
      spectrally resolved ultrafast supercontinuum transient absorption (SC-TA)
      measurements. We simultaneously probe the first three excitonic transitions. The
      transient spectra show the presence of bleaching of absorption for the 1S(h)
      1S(e) transition, as well as transients associated with the 1P(h)-1P(e)
      transition. We examine signatures of carrier multiplication (multiple excitons
      arising from a single absorbed photon) from analysis of the bleaching features in
      the limit of low absorbed photon numbers (left angle bracket N(abs) right angle
      bracket ~ 10(-2)) for pump photon energies from two to four times that of the
      band gap. The efficiency of multiple-exciton generation is discussed both in
      terms of the ratio between early- to long-time transient absorption signals and
      of a broadband global fit to the data. Analysis of the population dynamics shows
      that bleaching associated with biexciton population is red shifted with respect
      to the single exciton feature, which is in accordance with a positive binding
      energy for the biexciton.

PMID- 22149991
TI  - Bystander-type effects mediated by long-lived inflammatory signaling in
      irradiated bone marrow.
AB  - Radiation-induced bystander and abscopal effects, in which DNA damage is produced
      in nonirradiated cells as a consequence of communication with irradiated cells,
      indicate mechanisms of inducing damage and cell death additional to the
      conventional model of deposition of energy in the cell nucleus at the time of
      irradiation. In this study we show that signals generated in vivo in the bone
      marrow of mice irradiated with 4 Gy gamma rays 18 h to 15 months previously are
      able to induce DNA damage and apoptosis in nonirradiated bone marrow cells but
      that comparable signals are not detected at earlier times postirradiation or at
      doses below 100 mGy. Bone marrow cells of both CBA/Ca and C57BL/6 genotypes
      exhibit responses to signals produced by either irradiated CBA/Ca or C57BL/6
      mice, and the responses are mediated by the cytokines FasL and TNF-alpha
      converging on a COX-2-dependent pathway. The findings are consistent with
      indirect inflammatory signaling induced as a response to the initial radiation
      damage rather than to direct signaling between irradiated and nonirradiated
      cells. The findings also demonstrate the importance of studying tissue responses
      when considering the mechanisms underlying the consequences of radiation
      exposures.

PMID- 22149992
TI  - Harnessing autophagy for adoptive T-cell therapy.

PMID- 22149993
TI  - Immunotherapy synergizes with chemotherapy targeting pancreatic cancer.

PMID- 22149994
TI  - Chemokine axis as a therapeutic target to enhance the recruitment of Tregs and
      treat organ-specific autoimmune and inflammatory diseases.

PMID- 22149995
TI  - Future of immunotherapy for food allergy.

PMID- 22149997
TI  - Gram-positive bacteria: a major microbial 'turn-on' for invariant NKT cells.

PMID- 22149998
TI  - Conference scene: Recent advancements in immunotherapy.
AB  - Dendritic cells (DCs) mainly function to process/present antigens and thus
      initiate and shape the subsequent immune response. DCs are chiefly present within
      tissues in contact with the external environment and have a crucial role for
      maintaining immune homeostasis. Epithelial cells have been attracting
      considerable attention recently for they express a range of factors that
      influence the behavior of DCs. Organized by Euroscicon, this meeting focussed on
      integrating current knowledge and new paradigms surrounding the role of various
      DC subtypes and epithelial cells; their interaction with one another as well as
      with lymphocytes, microbial pathogens and commensal organisms. A wealth of
      experts currently researching this diverse field provided insight into these
      important interactions, their relevance to the medical setting and highlighted
      areas for future research.

PMID- 22149999
TI  - TroVax((r)) vaccine therapy for renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is the most common primary malignancy affecting the
      kidney. In the past decade, several well-designed clinical trials have shifted
      the treatment paradigm for RCC to favor targeted therapies as first-line agents.
      Recognition of the immunogenic nature of RCC has also resulted in the development
      of immunotherapy approaches with high-dose IL-2 treatment being the best
      established and associated with durable disease control. The lack of defined
      antigens in RCC has hindered more specific vaccine development. TroVax((r)) is a
      novel vaccine based on a modified vaccinia virus Ankara vector engineered to
      express the 5T4 tumor-associated antigen, found on over 95% of clear cell and
      papillary RCC tumors. The safety and efficacy of TroVax has been evaluated in
      several Phase I/II clinical trials and in a multicenter Phase III trial. This
      article will discuss the clinical background of RCC, the rationale for TroVax
      development, results of several TroVax clinical trials and future directions for
      optimizing TroVax therapy in patients with RCC and other cancers.

PMID- 22150000
TI  - Role of myeloid-derived suppressor cells in tumor immunotherapy.
AB  - Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that
      infiltrate human and experimental tumors and strongly inhibit anticancer immune
      response directly or by inducing regulatory T-lymphocyte activity. Consequently,
      MDSCs are important actors of cancer-induced immune tolerance and a major
      obstacle to efficiency of cancer immunotherapy. Several means of preventing MDSCs
      accumulation or inhibiting their immunosuppressive effect were recently
      discovered in cancer-bearing hosts, contributing to restoring antitumor immunity
      and consequently to control of tumor growth. In experimental tumor models,
      targeting MDSCs can enhance the effects of active or passive immunotherapy. While
      similar effects have not yet been noted in cancer-bearing patients, recent
      preclinical findings demonstrating that the selective toxicity of conventional
      chemotherapies such as gemcitabine and 5-fluorouracil on MDSCs might contribute
      to their anticancer effect provide impetus to pursue investigations to unravel
      novel therapeutics that target MDSCs in humans.

PMID- 22150001
TI  - Expression of cancer-testis genes in brain tumors: implications for cancer
      immunotherapy.
AB  - Cancer-testis (CT) genes have a restricted expression in normal tissues except
      testis and a wide range of tumor types. Testis is an immune-privileged site as a
      result of a blood barrier and lack of HLA class I expression on the surface of
      germ cells. Hence, if testis-specific genes are expressed in other tissues, they
      can be immunogenic. Expression of some CT genes in a high percentage of brain
      tumors makes them potential targets for immunotherapy. In addition, expression of
      CT genes in cancer stem cells may provide special targets for treatment of cancer
      recurrences and metastasis. The presence of antibodies against different CT genes
      in patients with advanced tumors has raised the possibility of polyvalent
      antitumor vaccine application.

PMID- 22150002
TI  - Principles of psychoneuroendocrinoimmunotherapy of cancer.
AB  - Recent advances in the knowledge of the mechanisms responsible for antitumor
      immunity have stimulated the elaboration of new cancer immunotherapeutic
      strategies. Moreover, more recent discoveries have demonstrated that immune
      responses are under a physiological modulatory control played by several
      neuroendocrine pathways, which explain the differences between the in vivo and in
      vitro immune responses. While until a few years ago the evaluation of the immune
      status of cancer patients was substantially established on the basis of clinical
      empirical criteria, recent discoveries of the antitumor cytokine network have
      allowed the biochemical bases of anticancer immunity to be defined, leading to
      new anticancer immunotherapeutic strategies, on the basis of patient
      neuroendocrine and neuroimmune status, in an attempt to correct the great number
      of cancer-related alterations on the basis of knowledge of the physiopathology of
      anticancer immunity. The rationale for cancer neuroimmunotherapy consists of the
      possibility to enhance the efficacy of the various immunotherapeutic strategies
      by a concomitant administration of antitumor cytokines (namely IL-2), in addition
      to neuroendocrine endogenous molecules (namely the pineal indole hormones), able
      to stimulate the anticancer immunoresponse by amplifying the anticancer reaction
      and/or by counteracting the generation of immunosuppressive events.

PMID- 22150003
TI  - Immunotherapeutic implication of IL-6 blockade.
AB  - IL-6 is a cytokine featuring redundancy and pleiotropic activity. While IL-6
      contributes to host defense against acute environmental stress, continuous IL-6
      production plays a significant pathological role in various autoimmune and
      chronic inflammatory diseases. To counter this drawback, tocilizumab, a humanized
      anti-IL-6 receptor antibody, was developed. Clinical trials have verified the
      efficacy of tocilizumab for patients with rheumatoid arthritis, Castleman's
      disease and systemic juvenile idiopathic arthritis, resulting in approval of this
      innovative biologic for their treatment. Moreover, a considerable number of case
      reports and pilot studies have indicated the beneficial effects of tocilizumab on
      other autoimmune and chronic inflammatory diseases. Further clinical studies to
      evaluate the efficacy and safety of tocilizumab for these diseases are essential.

PMID- 22150004
TI  - Immunotherapy against invasive mold infections.
AB  - Invasive infections due to filamentous fungi, such as Aspergillus spp.,
      Zygomycetes, Scedosporium and Fusarium spp., cause significant morbidity and
      mortality in immunocompromised patients with hematological malignancies,
      recipients of hematopoietic stem cell transplants and those with chronic
      granulomatous disease. Despite antifungal therapy, the outcome is often
      unfavorable in these patients; immune restoration is considered as the
      cornerstone of successful treatment. Important aspects of human immune response
      against fungi include effective innate immune response expressed as effective
      phagocytic functions and a balance between proinflammatory and regulatory
      adaptive immune responses. A number of immunomodulatory approaches, including the
      administration of enhancing cytokines, adoptive transfer of pathogen-specific T
      lymphocytes and granulocyte transfusions have been investigated as adjunctive
      treatments against serious mold infections. Despite encouraging in vitro and in
      vivo data, current clinical evidence is not sufficient to allow firm
      recommendations on the use of these immunomodulatory modalities in serious mold
      infections.

PMID- 22150007
TI  - Mutations in RNA splicing machinery in human cancers.

PMID- 22150006
TI  - SF3B1 and other novel cancer genes in chronic lymphocytic leukemia.
AB  - BACKGROUND: The somatic genetic basis of chronic lymphocytic leukemia, a common
      and clinically heterogeneous leukemia occurring in adults, remains poorly
      understood. METHODS: We obtained DNA samples from leukemia cells in 91 patients
      with chronic lymphocytic leukemia and performed massively parallel sequencing of
      88 whole exomes and whole genomes, together with sequencing of matched germline
      DNA, to characterize the spectrum of somatic mutations in this disease. RESULTS:
      Nine genes that are mutated at significant frequencies were identified, including
      four with established roles in chronic lymphocytic leukemia (TP53 in 15% of
      patients, ATM in 9%, MYD88 in 10%, and NOTCH1 in 4%) and five with unestablished
      roles (SF3B1, ZMYM3, MAPK1, FBXW7, and DDX3X). SF3B1, which functions at the
      catalytic core of the spliceosome, was the second most frequently mutated gene
      (with mutations occurring in 15% of patients). SF3B1 mutations occurred primarily
      in tumors with deletions in chromosome 11q, which are associated with a poor
      prognosis in patients with chronic lymphocytic leukemia. We further discovered
      that tumor samples with mutations in SF3B1 had alterations in pre-messenger RNA
      (mRNA) splicing. CONCLUSIONS: Our study defines the landscape of somatic
      mutations in chronic lymphocytic leukemia and highlights pre-mRNA splicing as a
      critical cellular process contributing to chronic lymphocytic leukemia.

PMID- 22150008
TI  - Telomerase activity in response to mild oxidative stress.
AB  - We have analysed telomerase activity to determine whether it can be modified when
      BCL-2 is endogenously overexpressed in response to a mild oxidative stress
      treatment as part of a survival mechanism, in contrast with an exogenous bcl-2
      overexpression due to a retroviral infection. Endogenous bcl-2 overexpression was
      induced after a low oxidative insult of H2O2 in mice primary lung fibroblasts and
      L929 cell, whereas bcl-2 exogenous overexpression was performed using a
      retroviral infection in L929 cells. Telomerase activity was quantified in Bcl-2
      overexpressing cells by the TRAP assay. When the cells were treated with
      different H2O2 concentrations, only those exposed to 50 MUM showed increased
      telomerase activity. This correlates with BCL-2 expression as part of the
      endogenous response to mild oxidative stress. Oxidative stress generated during
      the toxic mechanism of chemotherapeutic drugs might induce BCL-2 increment,
      enhancing telomerase activity and reactivating the oncogenic process. Clinical
      trials should take into consideration the possibility of telomerase activation
      following increased BCL-2 expression when treating patients with ROS (reactive
      oxygen species) generation by anti-cancer drugs.

PMID- 22150009
TI  - Protective effect of taurine on cardiotoxicity of the bufadienolides derived from
      toad (Bufo bufo gargarizans Canto) venom in guinea-pigs in vivo and in vitro.
AB  - In China, toad venom is an anti-inflammatory agent used in small doses for the
      treatment of various types of inflammation. Bufadienolides are cardioactive
      steroids responsible for the anti-inflammatory actions of toad venom. We studied
      the protective effect of taurine on the cardiotoxicity of bufadienolides in
      guinea-pigs. Bufadienolides (8 mg/kg) caused arrhythmias, cardiac dysfunction and
      death in guinea-pigs. Pretreatment with taurine (150, 300 mg/kg) significantly
      prevented bufadienolide-induced cardiotoxicity and reduced the mortality in vivo.
      Taurine markedly increased the cumulative doses of bufadienolides and
      resibufogenin required for lethal arrhythmia in ex vivo isolated guinea-pig
      heart. Taurine did not compromise the anti-inflammatory activity of the
      bufadienolides on concanavalin-A-stimulated proliferation of guinea-pig
      splenocytes in vitro. These data indicate that taurine can prevent bufadienolide
      induced cardiotoxicity and could be a novel antidote in combination with
      bufadienolide therapy.

PMID- 22150010
TI  - Virtual population generator for human cardiomyocytes parameters: in silico drug
      cardiotoxicity assessment.
AB  - BACKGROUND: The anatomical and histological parameters of the human ventricle
      depend on many factors including age and sex. Myocyte volume and electric
      capacitance are significant physiological parameters of left ventricle
      cardiomyocyte mathematical models. They allow the assessment of inter-individual
      variability during in vitro-in vivo extrapolation of the drug cardiotoxic effect.
      OBJECTIVE: The current research was carried out to analyze the relationship
      between age, human left ventricle cardiomyocyte volume, and electric capacitance
      in a healthy population. METHODS: In order to collect data describing
      cardiomyocyte volume and membrane area, literature searches were performed. It
      was assumed that the cardiomyocyte volume (VOL) and area (AREA) distribution have
      non-negative support and are skewed to the right. A log-linear model with
      constant variance was used. A simulation study was run to assess the influence of
      physiological parameters on action potential duration. RESULTS: The coefficient
      of determination for the proposed model R(2) = 0.95, that is, 95% of the
      variability observed in log cardiomyocyte volume can be explained by the
      estimated regression equation. To allow simple calculation and model performance
      validation, a simple Excel file was developed (Supplementary material).
      CONCLUSIONS: To the best of our knowledge, there is no other model available,
      combining age, cardiomyocyte volume, and area. The main limitations of the
      proposed models result from the assumptions made at the data analysis stage. The
      limited amount of information available in the literature and the lack of
      differentiation between sexes results in one common equation. The developed model
      is a part of the computational system for drug cardiotoxicity assessment.

PMID- 22150011
TI  - Chronic cervical spinal cord injury: DTI correlates with clinical and
      electrophysiological measures.
AB  - Diffusion tensor imaging (DTI) is rarely applied in spinal cord injury (SCI). The
      aim of this study was to correlate diffusion properties after SCI with
      electrophysiological and neurological measures. Nineteen traumatic cervical SCI
      subjects and 28 age-matched healthy subjects participated in this study. DTI data
      of the spinal cord were acquired with a Philips Achieva 3 T MR scanner using an
      outer volume suppressed, reduced field of view (FOV) acquisition with oblique
      slice excitation and a single-shot EPI readout. Neurological and
      electrophysiological measures, American Spinal Injury Association (ASIA)
      impairment scale scores, and motor (MEP) and somatosensory evoked potentials
      (SSEP) were assessed in SCI subjects. Fractional anisotropy (FA) values were
      decreased in the SCI subjects compared to the healthy subjects. In upper cervical
      segments, the decrease in FA was significant for the evaluation of the entire
      cross-sectional area of the spinal cord, and for corticospinal and sensory
      tracts. A decreasing trend was also found at the thoracic level for the
      corticospinal tracts. The decrease of DTI values correlated with the clinical
      completeness of SCI, and with SSEP amplitudes. The reduced DTI values seen in the
      SCI subjects are likely due to demyelination and axonal degeneration of spinal
      tracts, which are related to clinical and electrophysiological measures. A
      reduction in DTI values in regions remote from the injury site suggests their
      involvement with wallerian axonal degeneration. DTI can be used for the
      quantitative evaluation of the extent of spinal cord damage, and eventually to
      monitor the effects of future regeneration-inducing treatments.

PMID- 22150012
TI  - Influence of filler addition, storage medium and evaluation time on biaxial
      flexure strength and modulus of adhesive systems.
AB  - OBJECTIVE: This study evaluated the effects of filler addition, storage medium
      and time on biaxial flexural strength and flexural modulus of six adhesive
      systems. MATERIALS AND METHODS: The adhesives were either unfilled resins: Single
      Bond, Prime&Bond 2.1 and One-Step; or filled resins: Single Bond Plus, Prime&Bond
      NT and One-Step Plus. Resin discs of each product (0.5 mm thick * 6.0 mm
      diameter) were prepared using silicon molds (n = 10). The discs were stored dry,
      in water, mineral oil or ethanol for 1 week or 3 months before biaxial flexural
      testing. Data were statistically analyzed by 3-way ANOVA and Tukey's post-hoc
      test (alpha = 0.05). The specimens were tested in a universal testing machine at
      1.27 mm/min until failure occurred. RESULTS: In general, the storage in ethanol
      led to significantly lower flexural strength and flexural modulus values than the
      other storage conditions for all adhesives in both storage periods. Filler
      addition increased flexural strength and flexural modulus for Prime&Bond NT, when
      it was stored dry or in water for 1 week. For Single Bond Plus, the filler
      addition resulted in higher flexural modulus, when it was stored for 1 week in
      oil and in ethanol. No significant differences in flexural modulus were observed
      between One-Step and One-Step Plus in any storage medium. CONCLUSIONS: Results
      suggested that filler addition does not necessarily have to increase the flexural
      strength and flexural modulus. Ethanol and oil storages tended to yield opposite
      effects.

PMID- 22150013
TI  - Maternal and paternal age and twinning in the United States, 2004-2008.
AB  - AIMS: To determine the effects of increasing maternal age and related maternal
      and possibly paternal factors. METHODS: A US database of more than 8 million
      births was analyzed to determine the relationships between maternal age, maternal
      ethnicity, marital status, maternal smoking and paternal age on twinning rates.
      RESULTS: Twinning rates increased proportionally with maternal age. African
      American women had a higher twinning rate than Caucasian women. Hispanic, Asian
      and Native American women had comparatively lower rates than Caucasians. After
      controlling for ethnicity and other maternal factors, increasing maternal age was
      still related to increased twinning rates. Increased paternal age had a small but
      significant independent association with an increased rate of twinning.
      CONCLUSIONS: Both increasing maternal and paternal age are related to increased
      rates of twinning. This age effect is independent of other factors also
      associated with twinning.

PMID- 22150014
TI  - Retinal microvascular changes in low-birth-weight babies have a link to future
      health.
AB  - BACKGROUND: In utero insults that result in low-birth-weight (LBW) infants are
      now recognized risk factors for the development of vascular-related diseases in
      adulthood. Microcirculatory pathologies are believed to form a mechanistic link
      between fetal insult and the manifestation of illness in adulthood. OBJECTIVES:
      The challenge has been to investigate microcirculatory changes in vivo. The
      objective of this review is to determine whether LBW infants and individuals
      undergo abnormal microvascular changes and, if so, whether these changes can be
      objectively identified and measured by investigating retinal vessels. METHODS: An
      online publication search was carried out using the following keywords to
      identify and review relevant articles: retinal microvasculature, retinal vessels,
      small for gestation age, growth restriction, and intrauterine growth restriction.
      Articles published from 1980 to 2011 were considered. CONCLUSIONS: The ability of
      retinal imaging technology to assess and measure retinal microvasculature makes
      it a valuable assessment tool. The current tool is, however, unsuitable for non
      invasive assessment in infants and young children. Once this hurdle has been
      overcome, a longitudinal study of LBW individuals from infancy to adulthood, with
      regular retinal microvascular assessments, would help prove the mechanistic link
      between LBW and cardiovascular disease in adulthood.

PMID- 22150015
TI  - Consideration of reactivity to acute fish toxicity of alpha,beta-unsaturated
      carbonyl ketones and aldehydes.
AB  - To understand the key factor for fish toxicity of 11 alpha,beta-unsaturated
      carbonyl aldehydes and ketones, we used quantum chemical calculations to
      investigate their Michael reactions with methanethiol or glutathione. We used two
      reaction schemes, with and without an explicit water molecule (Scheme-1wat and
      Scheme-0wat, respectively), to account for the effects of a catalytic water
      molecule on the reaction pathway. We determined the energies of the reactants,
      transition states (TS), and products, as well as the activation energies of the
      reactions. The acute fish toxicities of nine of the carbonyl compounds were
      evaluated to correlate with their hydrophobicities; no correlation was observed
      for acrolein and crotonaldehyde. The most toxic compound, acrolein, had the
      lowest activation energy. The activation energy of the reaction could be
      estimated with Scheme-1wat but not with Scheme-0wat. The complexity of the
      reaction pathways of the compounds was reflected in the difficulty of the TS
      structure searches when Scheme-1wat was used with the polarizable continuum
      model. The theoretical estimations of activation energies of alpha,beta
      unsaturated carbonyl compounds with catalytic molecules or groups including
      hydrogen-bond networks may complement traditional tools for predicting the acute
      aquatic toxicities of compounds that cannot be easily obtained experimentally.

PMID- 22150016
TI  - Brazilian mothers with HIV: experiences with diagnosis and treatment in a human
      rights based health care system.
AB  - Drawing on in-depth interviews with a group of urban poor HIV-positive mothers in
      Northeastern Brazil, this essay examines their experiences with HIV medical
      diagnosis and treatment. It argues that strong social and religious networks as
      well as the Universal HIV treatment program provide Northeastern Brazilian
      mothers with forms of support that may be absent in other countries. It further
      suggests that more research be done to determine how particular forms of health
      care, such as the human rights-based approach that Brazil has taken to HIV/AIDS,
      inform patient-provider relationships.

PMID- 22150017
TI  - Encapsulation of a pressure-sensitive adhesive by spray-drying: microparticles
      preparation and evaluation of their crushing strength.
AB  - An industrial pressure-sensitive adhesive was microencapsulated by spray-drying
      using an aqueous colloidal ethylcellulose dispersion (Aquacoat(r) ECD)
      plasticised by triacetin to form the wall material. Unloaded (0:100) and adhesive
      loaded (25:75) particles were produced in a Buchi B-191 mini spray-dryer with
      product yields of 62% and 57%, respectively. Microparticles were spherical and
      narrow sized with mean D3,2 diameters of 3.165 +/- 0.001 and 5.544 +/- 0.105 um,
      respectively. The microparticles were found to redisperse well in water and
      exhibit enough stability in neutral and alkaline aqueous media to be further used
      in a coating slip. Crush tests on single microparticles with diameters ranging
      from 2 to 12 um were performed using a nanoindenter. They revealed that the
      crushing force of both kinds of microparticles increased linearly with their
      diameter and that the adhesive loading reduced the mechanical strength of the
      prepared microparticles.

PMID- 22150018
TI  - Preparation and evaluation of niosomes containing autoclaved Leishmania major: a
      preliminary study.
AB  - In this study, different positively charged niosomal formulations containing
      sorbitan esters, cholesterol and cetyl trimethyl ammonium bromide were prepared
      by film hydration method for the entrapment of autoclaved Leishmania major (ALM).
      Size distribution pattern and stability of niosomes were investigated by laser
      light scattering method and ALM encapsulation per cent was measured by the
      bicinchoninic acid method. Finally, the selected formulation was used for the
      induction of the immune response against cutaneous leishmaniasis in BALB/c mice.
      Size distribution curves of all the formulations followed a log-normal pattern
      and the mean volume diameter was in the range 7.57-15.80 um. The mean volume
      diameters were significantly increased by adding Tween to Span formulations (p <
      0.05). The percentage of ALM entrapped in all formulations varied between 14.88%
      and 36.65%. In contrast to ALM, in vivo studies showed that the niosomes
      containing ALM have a moderate effect in the prevention of cutaneous
      leishmaniasis in BALB/c mice.

PMID- 22150019
TI  - Completion of the life cycle of Sarcocystis zuoi , a parasite from the Norway
      rat, Rattus norvegicus.
AB  - Transmission experiments were performed to elucidate the life cycle of
      Sarcocystis zuoi found in Norway rats ( Rattus norvegicus ) in China. Two king
      rat snakes ( Elaphe carinata ) fed sarcocysts from the muscles of 4 naturally
      infected Norway rats shed sporocysts measuring 10.8 +/- 0.7 * 8.0 +/- 0.7 um,
      with a prepatent period of 8-9 days. Sporocysts from the intestine of 2
      experimentally infected king rat snakes were given to the laboratory Sprague
      Dawley (SD) rats ( R. norvegicus ) and Kunming (KM) mice ( Mus musculus ).
      Microscopic sarcocysts developed in the skeletal muscles of SD rats. No
      sarcocysts were observed in KM mice. Characters of ultrastructure and molecule of
      sarcocysts from SD rats were confirmed as S. zuoi . Our results indicate that
      king rat snake is the definitive host of S. zuoi .

PMID- 22150020
TI  - Characteristics of women who are pregnant with their first baby at an advanced
      age.
AB  - OBJECTIVE: To describe the background characteristics of women who gave birth to
      their first child at an advanced and very advanced maternal age, including their
      sociodemographic background, social relationships, health behavior, physical and
      mental health, and reproductive history. DESIGN: Cross-sectional data from the
      Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian
      Institute of Public Health. SETTING: Norway. Sample. 41 236 Norwegian-speaking
      nulliparous women. METHODS: Data were collected by the first questionnaire
      distributed in week 17 of pregnancy during the recruitment period 1999-2008. The
      distribution of descriptive variables in relation to age was investigated, by
      means of bivariate and multivariate logistic regression analyses. MAIN OUTCOME
      MEASURES: Advanced (33-37 years) and very advanced (>=38 years) maternal age.
      RESULTS: Women who had their first baby at an advanced or very advanced age
      differed from the younger women with regard to a wide range of background
      characteristics, and this difference was most pronounced for the very advanced
      group. Problems related to physical aging were more common (infertility, physical
      health problems, sleep problems, depression and fatigue). Of the sociodemographic
      factors; high annual income and low level of education were most strongly
      correlated with high maternal age, followed by single status, unemployment,
      unsatisfactory relationship with partner and unplanned pregnancy. CONCLUSIONS:
      Besides having more age-related reproductive and physical health problems, women
      who had their first baby at an advanced or very advanced age constituted a
      heterogeneous group characterized by either socioeconomic prosperity or
      vulnerability.

PMID- 22150021
TI  - Transfer of motor learning engages specific neural substrates during motor memory
      consolidation dependent on the practice structure.
AB  - The authors investigated how brain activity during motor-memory consolidation
      contributes to transfer of learning to novel versions of a motor skill following
      distinct practice structures. They used 1 Hz repetitive Transcranial Magnetic
      Stimulation (rTMS) immediately after constant or variable practice of an arm
      movement skill to interfere with primary motor cortex (M1) or dorsolateral
      prefrontal cortex (DLPFC). The effect of interference was assessed through skill
      performance on two transfer targets: one within and one outside the range of
      practiced movement parameters for the variable practice group. For the control
      (no rTMS) group, variable practice benefited delayed transfer performance more
      than constant practice. The rTMS effect on delayed transfer performance differed
      for the two transfer targets. For the within-range target, rTMS interference had
      no significant affect on the delayed transfer after either practice structure.
      However, for the outside-range target, rTMS interference to DLPFC but not M1
      attenuated delayed transfer benefit following variable practice. Additionally,
      for the outside-range target, rTMS interference to M1 but not DLPFC attenuated
      delayed transfer following constant practice. This suggests that variable
      practice may promote reliance on DLPFC for memory consolidation associated with
      outside-range transfer of learning, whereas constant practice may promote
      reliance on M1 for consolidation and long-term transfer.

PMID- 22150023
TI  - Diffusion-weighted MRI compared to FDG PET-CT in the staging and response
      assessment of Hodgkin lymphoma.

PMID- 22150024
TI  - The disruptive consequences of discourse fragmentation in the organization and
      delivery of health care: a look into diabetes.
AB  - The aim of this study is to contribute to a better understanding about how
      discourse fragmentation is affecting the way doctors perceive the patient's role
      and expectations that are being redefined under the influence of media and other
      information sources. The diabetes case provides the empirical evidence to support
      the fragmentation thesis. This condition offers a unique mix of complexity,
      scope, and controversy to understand the dialectics of discourse fragmentation.
      Through a combined analysis of media discourse and experts' discourse
      (researchers and clinicians), this article describes the connections between the
      macro (the realm of the public sphere) and the micro (the localized medical
      practice) in the context of health care delivery. The study concludes that a
      fragmented media discourse tends at the same time to nourish the public
      perception about the "diabetes complexities" (a multifaceted and growing
      epidemic), and to normalize some emerging concepts such as "prediabetes" and
      metabolic syndrome. This fragmentation seems to have a double-edged sword effect
      on doctor-patient relationships; in some occasions the atomized discourse about
      diabetes has a clear disruptive impact on their medical practice, adding an
      "extra burden" to the disease management, while in other opportunities it has a
      more convergent effect facilitating the dialogue and the interaction between the
      actors.

PMID- 22150025
TI  - Status of end organs in newly detected rural essential hypertensives: a study
      from southern India.
AB  - BACKGROUND: Hypertension is associated with end-organ damage (EOD). Since EOD is
      a risk factor for cardio- and cerebrovascular complications, it is a major
      requirement for these to be detected, prevented, and treated. OBJECTIVE: The
      objectives of our study were to determine out the prevalence of EOD in newly
      detected rural essential hypertensives, identify the pattern of EOD involved, and
      also assess the interrelationship among them. METHODS: A total of 147 consecutive
      patients with newly diagnosed essential hypertension and, attending the
      outpatient clinic, were included in this study based on a set of inclusion and
      exclusion criteria. Patients with comorbid illnesses were excluded from the
      investigation. The significance of a range of variables involved was evaluated
      using statistical software. RESULTS: Amongst the cases, there were 79 males (M)
      and 68 females (F). Their mean and median ages were 55 (standard deviation (SD) =
      9.90) and 54 years, respectively. Of these 86% (70 M and 56 F) had one or more
      EODs; an observation which was very close to statistically significant (P =
      .054). In our patients, microalbuminuria (35%), diastolic dysfunction (59%),
      increased left ventricular (LV) mass (68%) and retinopathy (69%) were
      particularly notable. Increased LV mass had a strong association with
      retinopathy, microalbuminuria, and diastolic dysfunction. CONCLUSION: The
      presence of one or more EODs in newly detected hypertension indicates widespread
      vascular damage that carries a high risk for cardio- and cerebrovascular
      morbidity and mortality. Hence, there is an urgent requirement not only for
      complete evaluation but also to stimulate an increased awareness amongst
      physicians and the general public, regarding the control of blood pressure.

PMID- 22150026
TI  - Chemical constituents and allelopathic and antioxidant activities of
      Alchorneopsis floribunda Mull. Arg. (Euphorbiaceae).
AB  - Chemical investigation of extracts from the stems and leaves of Alchorneopsis
      floribunda Mull. Arg., collected in the Amazon region, was performed. The main
      isolated compounds were triterpenes (alpha-amyrin, beta-amyrin, lupeol, betulin,
      betulinic acid, uvaol, erythrodiol and oleanolic acid) and phenolic acid
      derivatives from 4-hydroxybenzoic acid (gallic and protocatechuic acids and
      isocorilagin). In the germination assays, high inhibitory allelopathic effects of
      the extracts and isocorilagin were observed and 2,2-diphenyl-1-picrylhydrazyl
      radical scavenging activity of isocorilagin was higher than those of the
      standards used (Trolox and butylated hydroxyanisole). This is the first chemical
      study of the genus Alchorneopsis (Euphorbiaceae).

PMID- 22150028
TI  - Raman spectroscopic investigation of the effects of cosmetic formulations on the
      constituents and properties of human skin.
AB  - OBJECTIVE: This study aimed to investigate the biochemical alterations in
      hydration and skin proteins, which are associated with the skin aging process,
      caused by cosmetic use. BACKGROUND DATA: Many techniques have been used to assess
      the effectiveness of cosmetics' hydrating and anti-aging effects on skin.
      Recently, Raman spectroscopy has been shown to be a powerful, noninvasive tool
      that can monitor changes in the biomolecules of the skin in real time. MATERIALS
      AND METHODS: Were analyzed human skin in vivo at the beginning of the experiment
      (T0) and after 30 (T30) and 60 (T60) days of continuous use of a cosmetic
      product. Fourier-transform and dispersive Raman spectroscopy were the used to
      examine the periorbicular right lateral eye region of 16 female Brazilian
      volunteers, aged 60-75 years. Multivariate statistical analysis of principal
      components analysis (PCA) and linear discriminant analysis were performed on all
      Raman spectra. RESULTS: Using the cosmetic product for 30 days increased the
      intensity of the Raman bands for collagen, amide III (1250-1350 cm(-1)) for
      proteins, and the water (OH) stretching mode at 3250 cm(-1), suggesting that the
      treatment was effective. The changes observed at T30 were not sustained at the
      same intensity for 60 days. Intensity variations in other bands may be related to
      changes in the organization of the epidermis at the dermal matrix. CONCLUSIONS:
      The application of cosmetics with active moisturizing and anti-aging properties
      helps to maintain the skin's protective barrier and to slow the intrinsic and
      extrinsic aging processes of the skin.

PMID- 22150027
TI  - Autofluorescence in BrdU-positive cells and augmentation of regeneration kinetics
      by riboflavin.
AB  - The earthworm, Eudrilus eugeniae, has a prodigious ability to regenerate lost
      segments. The skin of the worm has an outermost epidermal layer followed by a
      thick circular muscle layer and an innermost thin longitudinal cell layer. During
      the process of regeneration, the circular muscle layer decreased in thickness,
      and longitudinal cell layer increased. The histological analysis of the
      regenerated worm shows that the longitudinal cell layer forms the regeneration
      blastema. BrdU-labeling retention assay confirmed that the circular muscle and
      longitudinal cell layers have BrdU-positive cells, which migrate from the
      adjacent segments to the regeneration blastema. In addition, it was noted that
      the cells of the earthworm, E. eugeniae, have the property of autofluorescence.
      Autofluorescence was found in the cytoplasm, but not in the nucleus. It has been
      also found that the major source for autofluorescence is riboflavin. Further, it
      was also demonstrated that supplementation with riboflavin increases the rate of
      regeneration, while regeneration was hampered by reduced levels of riboflavin.
      The importance of riboflavin in regeneration was also confirmed by rescue assay.
      In addition, it was also identified that BrdU-positive cells are highly
      fluorescent compared to the surrounding cells.

PMID- 22150029
TI  - Development of a real-time method to detect DNA degradation in forensic samples.
AB  - Knowledge of the degradation state of evidentiary DNA samples would allow
      selection of the appropriate analysis method (standard short tandem repeats
      [STRs] vs. mini STRs vs. mtDNA). This article describes the development of a
      Plexor(r) technology/real-time PCR DNA degradation detection assay, which uses a
      common forward primer and two reverse primers (different fluorophores) to
      generate two Alu amplicons (63 and 246 bp). This very sensitive assay was
      optimized for reaction volume, cycle number, anneal/extend time, and temperature.
      Using DNA samples degraded with DNaseI, the ratio of the concentration of the
      short amplicon to the concentration of the long amplicon (degradation ratio) was
      increased versus time of degradation. Experiments were performed on a variety of
      environmentally degraded samples (age, sunlight, heat) and with seven commonly
      encountered forensic inhibitors. The degradation ratio was found to predict the
      observed loss of larger STR loci seen in the analysis of comprised samples.

PMID- 22150030
TI  - Seroreactivity to E. coli outer membrane protein C antibodies in active
      inflammatory bowel disease; diagnostic value and correlation with phylogroup B2
      E. coli infection.
AB  - BACKGROUND: Several serologic tests, including anti-outer membrane porin C
      antibody (Omp C), are used for screening and as marker of disease course in
      inflammatory bowel diseases (IBD). Our aim was to investigate possible
      differences in Omp C level in patients with active and inactive IBD compared to
      controls. METHODS: All blood samples were tested for Omp C. Disease activity was
      evaluated by Harvey Bradshaw Index, Simple Clinical Activity Index and Modified
      Pouchitis Disease Activity Index. RESULTS: Blood samples were collected from 113
      patients and 60 controls. Patients with active IBD did not have a higher level of
      Omp C than patients in remission. Surprisingly, in patients with active Crohn's
      disease a significantly lower level of Omp C was found compared with patients
      with inactive Crohn's disease (p < 0.05). All other groups among patients with
      IBD did have a significantly higher level of Omp C, compared with controls,
      including patients with acute gastroenteritis (p < 0.05). Although IBD patients
      with phylogroup B2 E. coli cultured from their fecal samples, were more likely to
      have a positive Omp C test (p < 0.05), this could not explain the low Omp C level
      in the subgroup of patients with active Crohn's disease. CONCLUSIONS: Omp C titer
      was not raised in patients with active IBD compared with patients in remission.
      In addition, there was no difference in Omp C level in patients with active
      Crohn's disease compared with controls. These observations do not support the use
      of Omp C serology testing, either in disease activity assessment, or in screening
      for active Crohn's disease.

PMID- 22150031
TI  - An update on the management and treatment of deep vein thrombosis.
AB  - Deep venous thrombosis (DVT) with its associated complications of pulmonary
      embolism and postthrombotic syndrome are an important cause of morbidity and
      mortality. This review article provides an overview of the pathophysiology, risk
      factors and the guidelines for thromboprophylaxis. It also reviews the available
      modalities in the diagnosis and treatment of DVT. The newer methods of treatment
      are also discussed. 

PMID- 22150032
TI  - Valedictory editorial.

PMID- 22150033
TI  - Discussing overall prognosis with the very elderly.

PMID- 22150034
TI  - Learning about the safety of drugs--a half-century of evolution.

PMID- 22150036
TI  - Norovirus vaccine against experimental human Norwalk Virus illness.
AB  - BACKGROUND: Noroviruses cause epidemic and sporadic acute gastroenteritis. No
      vaccine is available to prevent norovirus illness or infection. METHODS: We
      conducted a randomized, double-blind, placebo-controlled, multicenter trial to
      assess the safety, immunogenicity, and efficacy of an investigational,
      intranasally delivered norovirus viruslike particle (VLP) vaccine (with chitosan
      and monophosphoryl lipid A as adjuvants) to prevent acute viral gastroenteritis
      after challenge with a homologous viral strain, Norwalk virus (genotype GI.1).
      Healthy adults 18 to 50 years of age received two doses of either vaccine or
      placebo and were subsequently inoculated with Norwalk virus and monitored for
      infection and gastroenteritis symptoms. RESULTS: Ninety-eight persons were
      enrolled and randomly assigned to receive vaccine (50 participants) or placebo
      (48 participants), and 90 received both doses (47 participants in the vaccine
      group and 43 in the placebo group). The most commonly reported symptoms after
      vaccination were nasal stuffiness, nasal discharge, and sneezing. Adverse events
      occurred with similar frequency among vaccine and placebo recipients. A Norwalk
      virus-specific IgA seroresponse (defined as an increase by a factor of 4 in serum
      antibody levels) was detected in 70% of vaccine recipients. Seventy-seven of 84
      participants inoculated with Norwalk virus were included in the per-protocol
      analysis. Vaccination significantly reduced the frequencies of Norwalk virus
      gastroenteritis (occurring in 69% of placebo recipients vs. 37% of vaccine
      recipients, P=0.006) and Norwalk virus infection (82% of placebo recipients vs.
      61% of vaccine recipients, P=0.05). CONCLUSIONS: This norovirus VLP vaccine
      provides protection against illness and infection after challenge with a
      homologous virus. (Funded by LigoCyte Pharmaceuticals and the National Institutes
      of Health; ClinicalTrials.gov number, NCT00973284.).

PMID- 22150037
TI  - Inflammatory cortical demyelination in early multiple sclerosis.
AB  - BACKGROUND: Cortical disease has emerged as a critical aspect of the pathogenesis
      of multiple sclerosis, being associated with disease progression and cognitive
      impairment. Most studies of cortical lesions have focused on autopsy findings in
      patients with long-standing, chronic, progressive multiple sclerosis, and the
      noninflammatory nature of these lesions has been emphasized. Magnetic resonance
      imaging studies indicate that cortical damage occurs early in the disease.
      METHODS: We evaluated the prevalence and character of demyelinating cortical
      lesions in patients with multiple sclerosis. Cortical tissues were obtained in
      passing during biopsy sampling of white-matter lesions. In most cases, biopsy was
      done with the use of stereotactic procedures to diagnose suspected tumors.
      Patients with sufficient cortex (138 of 563 patients screened) were evaluated for
      cortical demyelination. Using immunohistochemistry, we characterized cortical
      lesions with respect to demyelinating activity, inflammatory infiltrates, the
      presence of meningeal inflammation, and a topographic association between
      cortical demyelination and meningeal inflammation. Diagnoses were ascertained in
      a subgroup of 77 patients (56%) at the last follow-up visit (at a median of 3.5
      years). RESULTS: Cortical demyelination was present in 53 patients (38%) (104
      lesions and 222 tissue blocks) and was absent in 85 patients (121 tissue blocks).
      Twenty-five patients with cortical demyelination had definite multiple sclerosis
      (81% of 31 patients who underwent long-term follow-up), as did 33 patients
      without cortical demyelination (72% of 46 patients who underwent long-term follow
      up). In representative tissues, 58 of 71 lesions (82%) showed CD3+ T-cell
      infiltrates, and 32 of 78 lesions (41%) showed macrophage-associated
      demyelination. Meningeal inflammation was topographically associated with
      cortical demyelination in patients who had sufficient meningeal tissue for study.
      CONCLUSIONS: In this cohort of patients with early-stage multiple sclerosis,
      cortical demyelinating lesions were frequent, inflammatory, and strongly
      associated with meningeal inflammation. (Funded by the National Multiple
      Sclerosis Society and the National Institutes of Health.).

PMID- 22150035
TI  - Three months of rifapentine and isoniazid for latent tuberculosis infection.
AB  - BACKGROUND: Treatment of latent Mycobacterium tuberculosis infection is an
      essential component of tuberculosis control and elimination. The current standard
      regimen of isoniazid for 9 months is efficacious but is limited by toxicity and
      low rates of treatment completion. METHODS: We conducted an open-label,
      randomized noninferiority trial comparing 3 months of directly observed once
      weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination
      therapy group) with 9 months of self-administered daily isoniazid (300 mg)
      (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were
      enrolled from the United States, Canada, Brazil, and Spain and followed for 33
      months. The primary end point was confirmed tuberculosis, and the noninferiority
      margin was 0.75%. RESULTS: In the modified intention-to-treat analysis,
      tuberculosis developed in 7 of 3986 subjects in the combination-therapy group
      (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group
      (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of
      treatment completion were 82.1% in the combination-therapy group and 69.0% in the
      isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to
      an adverse event were 4.9% in the combination-therapy group and 3.7% in the
      isoniazid-only group (P=0.009). Rates of investigator-assessed drug-related
      hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001). CONCLUSIONS: The use
      of rifapentine plus isoniazid for 3 months was as effective as 9 months of
      isoniazid alone in preventing tuberculosis and had a higher treatment-completion
      rate. Long-term safety monitoring will be important. (Funded by the Centers for
      Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number,
      NCT00023452.).

PMID- 22150038
TI  - Clinical practice. A request for abortion.

PMID- 22150039
TI  - The pathogenesis of rheumatoid arthritis.

PMID- 22150040
TI  - Images in clinical medicine. Blindness after fat injections.

PMID- 22150041
TI  - Case records of the Massachusetts General Hospital. Case 37-2011. A 9-month-old
      boy with recurrent tachypnea and respiratory distress.

PMID- 22150042
TI  - Practical preventive therapy for tuberculosis?

PMID- 22150043
TI  - Inflammation in multiple sclerosis--sorting out the gray matter.

PMID- 22150045
TI  - Azithromycin for prevention of exacerbations of COPD.

PMID- 22150046
TI  - Azithromycin for prevention of exacerbations of COPD.

PMID- 22150047
TI  - Azithromycin for prevention of exacerbations of COPD.

PMID- 22150048
TI  - Azithromycin for prevention of exacerbations of COPD.

PMID- 22150050
TI  - Ranibizumab and bevacizumab for AMD.

PMID- 22150051
TI  - Safe preparation and administration of intravitreal bevacizumab injections.

PMID- 22150053
TI  - Drug-resistant epilepsy.

PMID- 22150054
TI  - Drug-resistant epilepsy.

PMID- 22150055
TI  - Drug-resistant epilepsy.

PMID- 22150056
TI  - Thrombopoietin-receptor agonists for immune thrombocytopenia.

PMID- 22150057
TI  - Myeloma and second primary cancers.

PMID- 22150058
TI  - Images in clinical medicine. Internal-carotid-artery dissection and cranial-nerve
      palsies.

PMID- 22150059
TI  - The role of IgE in difficult-to-treat asthma. Of compliance and competence.

PMID- 22150061
TI  - Paroxysmal sympathetic hyperactivity after traumatic brain injury: clinical and
      prognostic implications.
AB  - A proportion of patients surviving severe traumatic brain injury (TBI) have
      symptoms suggestive of excessive sympathetic discharge, here termed paroxysmal
      sympathetic hyperactivity (PSH). The goals of this study were: (1) to describe
      the clinical associations and radiological findings of PSH, its incidence, and
      features in subjects with severe TBI in the intensive care unit (ICU); (2) to
      investigate the potential role of increased intracranial pressure in the
      pathogenesis of PSH; and (3) to determine the prognostic influence of PSH during
      the ICU stay, on discharge from the ICU, and at 12 months post-injury. A
      prospective cohort study was undertaken of all ICU admissions with severe TBI
      older than 14 years over an 18-month period. The PSH symptoms consisted of
      paroxysmal increases in blood pressure, respiratory rate, and heart rate;
      worsening level of consciousness; muscle rigidity; and hyperhidrosis. Subjects
      demonstrating PSH episodes were compared with a group of non-PSH consecutive
      subjects studied over the first 6 months of the study period. Data were recorded
      on the clinical variables associated with PSH episodes, early post-injury
      cerebral CT findings, and neurological status at 1 year. Of 179 severe TBI
      patients admitted over the study period, 18 (10.1%) experienced PSH. Injury
      severity-related variables (e.g., initial APACHE II score, admission coma level,
      and proportion with intracranial hypertension) were similar between the two
      groups. The PSH group had a longer ICU stay and a greater incidence of infectious
      complications. At 1 year post-injury, 20% of this group demonstrated ongoing PSH
      episodes. Over 18 months, 10.1% of admissions following severe TBI demonstrated
      PSH features in ICU. Subjects with PSH had a longer ICU stay and higher rate of
      complications, although this did not appear to compromise their long-term
      neurological recovery.

PMID- 22150062
TI  - A role for immunophilins in cellular signalling in health and disease.

PMID- 22150063
TI  - Organ donation after cardiac death from withdrawal of life support in patients
      with amyotrophic lateral sclerosis.
AB  - OBJECTIVE: Donation after cardiac death (DCD) or donation of organs after removal
      of life support is an accepted means of organ retrieval that usually occurs in
      the setting of sudden illness but has not been described in people with
      progressive neurologic illness. We report DCD in two people with progressive
      amyotrophic lateral sclerosis (ALS). METHODS: Case series at an academic medical
      center of two men with progressive ALS who underwent withdrawal of artificial
      life support, rapid cardiac death, and subsequent organ donation. The primary
      outcome was donation of organs in concordance with patient and family wishes.
      RESULTS: Both patients underwent peaceful withdrawal of life support in the
      presence of family, and multiple organs were donated. CONCLUSIONS: Patients may
      legally and ethically refuse life-sustaining care. These patients considered
      their lives to be more burdensome than beneficial near the end of their lives,
      both carefully planned the time and circumstance of their deaths, and both
      fulfilled a long-standing desire to donate their organs. This study describes a
      potential opportunity for patients with progressive neurologic illness.

PMID- 22150064
TI  - Treatment of lumbar intervertebral disc herniation using C-arm fluoroscopy guided
      target percutaneous laser disc decompression.
AB  - OBJECTIVE: To evaluate the safety and therapeutic efficacy of target percutaneous
      laser disc decompression (T-PLDD) for the treatment of lumbar disc herniation.
      BACKGROUND DATA: PLDD using the Nd:YAG laser has been regarded as an effective
      alternative treatment for disc herniation. However, all the previous studies were
      concentrated on vaporizing the nucleus pulposus in the intervertebral space. We
      hypothesize that insertion of the needle into the extruded part of the nucleus
      pulposus will decrease its volume and provide superior clinical effects compared
      to therapies that decrease the volume of the intradiscal nucleus pulposus.
      MATERIALS AND METHODS: A total of 25 patients suffering from posterolateral
      extruded but nonsequestered lumbar intervertebral disc herniation were treated
      with T-PLDD. After treatment, the patients were followed up and the therapeutic
      effect was assessed at 1, 3, 6, and 12 months using the modified MacNab criteria.
      RESULTS: The success rate was 80.0% (18 of 25), 88.0% (22 of 25), 92.0% (23 of
      25), and 92.0% (23 of 25) at 1, 3, 6, and 12 months respectively. No serious
      complications occurred in any of the patients. Furthermore, we did not observe
      any neurological sequelae. CONCLUSIONS: T-PLDD can significantly decrease pain
      and improve function of patients who have extruded but nonsequestered lumbar
      intervertebral disc herniation.

PMID- 22150065
TI  - Microhardness of radicular dentin treated with 980-nm diode laser and different
      irrigant solutions.
AB  - OBJECTIVE: The aim of this study was to evaluate the microhardness of radicular
      dentin after treatment with 980-nm diode laser and different irrigant solutions.
      BACKGROUND DATA: There are few reports of the consequences of diode laser
      irradiation emitted at 980 nm on the mechanical properties of dentin. METHODS:
      Seventy-two single canal, human canines with complete root formation were
      randomly distributed among three groups (n=24), according to the irrigant
      solution used in the biomechanical preparation: distilled water; 1% NaOCl; and,
      1% NaOCl + 17% EDTA. These groups subsequently were divided into three subgroups
      (n=8), according to the diode laser parameter: no irradiation (control); 1.5
      W/100 Hz; and 3.0 W/100 Hz. Laser was applied with helicoidal movements for 20
      sec. Roots were sectioned in slices and the fragment corresponding to the middle
      third was submitted to the microhardness test (KHN) at depths of 30, 90, 150, and
      300 MUm. RESULTS: ANOVA and Tukey tests showed that the microhardness of the
      groups irradiated with 1.5 W/100 Hz (49.7+/-11.2) and 3.0 W/100 Hz (50.6+/-11.9)
      were statistically similar to each other (p>0.05) and different (p<0.05) from the
      non-irradiated group (45.0+/-9.7). Higher microhardness values were obtained at
      150 MUm (49.2+/-11.0) and 300 MUm (52.3+/-11.3) which were similar among
      themselves and different (p<0.05) only at the depth of 30 MUm (44.4+/-10.5). No
      differences were found among the irrigant solutions (p>0.05). CONCLUSIONS: The
      microhardness of the radicular dentin increased after irradiation with 980-nm
      diode laser.

PMID- 22150066
TI  - Novel mutations in microsomal triglyceride transfer protein including maternal
      uniparental disomy in two patients with abetalipoproteinemia.

PMID- 22150067
TI  - Nocturnal stomatal conductance responses to rising [CO2], temperature and
      drought.
AB  - The response of nocturnal stomatal conductance (g(s,n)) to rising atmospheric
      CO(2) concentration ([CO(2)]) is currently unknown, and may differ from responses
      of daytime stomatal conductance (g(s,d)). Because night-time water fluxes can
      have a significant impact on landscape water budgets, an understanding of the
      effects of [CO(2)] and temperature on g(s,n) is crucial for predicting water
      fluxes under future climates. Here, we examined the effects of [CO(2)] (280, 400
      and 640 MUmol mol(-1)), temperature (ambient and ambient + 4 degrees C) and
      drought on g(s,n,) and g(s,d) in Eucalyptus sideroxylon saplings. g(s,n) was
      substantially higher than zero, averaging 34% of g(s,d). Before the onset of
      drought, g(s,n) increased by 85% when [CO(2)] increased from 280 to 640 MUmol
      mol(-1), averaged across both temperature treatments. g(s,n) declined with
      drought, but an increase in [CO(2)] slowed this decline. Consequently, the soil
      water potential at which g(s,n) was zero (Psi(0)) was significantly more negative
      in elevated [CO(2)] and temperature treatments. g(s,d) showed inconsistent
      responses to [CO(2)] and temperature. g (s,n) may be higher in future climates,
      potentially increasing nocturnal water loss and susceptibility to drought, but
      cannot be predicted easily from g(s,d). Therefore, predictive models using
      stomatal conductance must account for both g(s,n) and g(s,d) when estimating
      ecosystem water fluxes.

PMID- 22150068
TI  - Linear and non-linear relationships between soil sorption and hydrophobicity.
AB  - The relationship between log K (oc) and log P was examined by use of a large
      dataset. For most of the hydrophobic compounds (e.g. 0.5 < log P < 7.5), the
      organic carbon content plays a dominant role in soil sorption and the sorption
      coefficient is linearly related to the octanol/water partition coefficient. For
      hydrophilic compounds (e.g. log P < 0.5), hydrophobic sorption becomes less
      significant. The hydrophilic contribution to sorption is equal to, or higher
      than, the hydrophobic contribution to sorption, resulting in the observed K (oc)
      values being higher than those predicted from their log P values. For highly
      hydrophobic compounds (e.g. log P > 7.5), log K (oc) decreases with increasing
      hydrophobicity because of a lack of chemical availability due to low solubility.
      A linear solvation energy relationship shows that the sorption potential
      increases with increasing molecular size by increasing the dispersion
      interactions between the chemical and soil organic phase. The sorption potential
      decreases with increase in the basicity of hydrophobic compounds by increasing
      the H-bonding of chemicals with water. Principal component analysis shows that
      the octanol/water system is the closest system, but not an ideal surrogate, to
      describe the soil sorption for hydrophobic compounds as compared with other
      solvent/water partition systems.

PMID- 22150069
TI  - Mitochondrial and metabolic-based protective strategies in Huntington's disease:
      the case of creatine and coenzyme Q.
AB  - Huntington's disease (HD) is a neurodegenerative genetic disorder caused by an
      expansion of CAG repeats in the HD gene encoding for huntingtin (Htt), resulting
      in progressive death of striatal neurons, with clinical symptoms of chorea,
      dementia and dramatic weight loss. Metabolic and mitochondrial dysfunction caused
      by the expanded polyglutamine sequence have been described along with other
      mechanisms of neurodegeneration previously described in human tissues and animal
      models of HD. In this review, we focus on mitochondrial and metabolic
      disturbances affecting both the central nervous system and peripheral cells,
      including mitochondrial DNA damage, mitochondrial complexes defects, loss of
      calcium homeostasis and transcriptional deregulation. Glucose abnormalities have
      also been described in peripheral tissues of HD patients and in HD animal and
      cellular models. Moreover, there are no effective neuroprotective treatments
      available in HD. Thus, we briefly discuss the role of creatine and coenzyme Q10
      that target mitochondrial dysfunction and impaired bioenergetics and have been
      previously used in HD clinical trials.

PMID- 22150071
TI  - Two cases of acute propane/butane poisoning in prison.
AB  - Hydrocarbon inhalation is seldom chosen as a means to commit suicide. This
      practice is exclusively a prerogative of the prison population; it is, however,
      only exceptionally found in this environment. The two cases of lethal inhalation
      of propane/butane gas observed by us over a very short time occurred in this
      context. Toxicologic analyses were performed by means of gas chromatography (head
      space) and revealed a propane/butane mixture in all specimens (heart blood, bile,
      and urine) except vitreous humor. Although fatal arrhythmia posthydrocarbon gas
      abuse is well known, the concentrations of the two hydrocarbons were sufficient
      to induce death by asphyxiation and were distributed (fairly) homogeneously in
      all biological fluids and organs examined, a parameter permitting one to assume
      that death occurred within a relatively short period of time. The absence of
      finding in vitreous humor and the trace amount in urine suggests that both men
      died very quickly.

PMID- 22150070
TI  - Stress-linked cortisol concentrations in hair: what we know and what we need to
      know.
AB  - Cortisol has major impacts upon a range of physiological homeostatic mechanisms
      and plays an important role in stress, anxiety and depression. Although
      traditionally described as being solely synthesised via the hypothalamic
      pituitary-adrenal (HPA) axis, recent animal and human studies indicate that
      cortisol may also be synthesised via a functionally-equivalent 'peripheral' HPA
      like process within the skin, principally within hair follicles, melanocytes,
      epidermal melanocytes and dermal fibroblasts. Current data indicate that basal
      levels of cortisol within hair vary across body regions, show diurnal variation
      effects, respond to the onset and cessation of environmental stressors, and may
      demonstrate some degree of localisation in those responses. There are conflicting
      data regarding the presence of variability in cortisol concentrations across the
      length of the hair shaft, thus challenging the suggestion that hair cortisol may
      be used as a historical biomarker of stress and questioning the primary origin of
      cortisol in hair. The need to comprehensively 'map' the hair cortisol response
      for age, gender, diurnal rhythm and responsivity to stressor type is discussed,
      plus the major issue of if, and how, the peripheral and central HPA systems
      communicate.

PMID- 22150072
TI  - ERK1/2 and Akt pathway activated during (3R,6R)-bassiatin(1)-induced apoptosis in
      MCF-7 cells.
AB  - (3R,6R)-bassiatin(1) was isolated from the endogenous fungus, Fusarium oxysporum
      J8-1-2. Previous studies showed that (3R,6R)-bassiatin(1) has anti-oestrogen
      properties which make it cytotoxic to ER (oestrogen receptor)-positive breast
      cancer cells (MCF-7) by cell cycle arrest and induction of apoptosis. (3R,6R)
      bassiatin(1) suppresses mRNA and protein expression of the ERalpha and oestrogen
      responsive genes of cyclin D1 and PR. We have investigated the interaction
      between (3R,6R)-bassiatin(1) and ERalpha and followed the roles of ERK
      (extracellular-signal-regulated kinase), Akt and GSK3beta (glycogen synthase
      kinase 3beta) during (3R,6R)-bassiatin(1)-induced apoptosis of MCF-7 cells.
      (3R,6R)-bassiatin(1) competed with E2 (17beta-estradiol) for ERalpha active sites
      to inhibit ERalpha activation. However, while ERK1/2 and Akt were activated,
      GSK3beta was inactivated during (3R,6R)-bassiatin(1)-induced apoptosis,
      suggesting that this compound is indeed an anti-oestrogen agent that can also
      activate the survival signalling pathway. Apoptosis caused by (3R,6R)
      bassiatin(1) may be related to activation of ERK.

PMID- 22150074
TI  - Cell individuality: the bistable gene expression of the type III secretion system
      in Dickeya dadantii 3937.
AB  - Dickeya dadantii 3937 is a gram-negative phytopathogenic bacterium that expresses
      genes encoding a type III secretion system (T3SS) in a bistable pattern when
      cultured in a homogeneous minimal media. In this work, we further characterized
      the bistable gene expression of T3SS at the single-cell level. We demonstrated
      that bistable expression of the HrpL-regulon genes, such as hrpA and hrpN, is
      controlled by the same regulatory mechanism. We also showed that the expression
      level of the T3SS master regulatory gene hrpL plays an important role in the
      development of the bistable expression of hrpA. A high expression level of hrpL
      is required but unable to guarantee the high-state expression of hrpA in a cell.
      In addition, bistable expression patterns of T3SS genes in other gram-negative
      pathogens of the Enterobacteriaceae and Pseudomonadaceae families were also
      described in this study. This suggests that the T3SS bistability might be a
      conserved population behavior in several gram-negative bacterial pathogens.

PMID- 22150075
TI  - Ammonium secretion during Colletotrichum coccodes infection modulates salicylic
      and jasmonic acid pathways of ripe and unripe tomato fruit.
AB  - The postharvest pathogens Colletotrichum coccodes remains quiescent after
      infection of unripe fruit. However, during fruit ripening, the pathogen assumes a
      necrotrophic life style, rapidly colonizing the tissue. C. coccodes secretes
      ammonium during germination and colonization of host tissue that induces host
      programmed cell death. We further examined the role of ammonia in the infection
      process by analyzing transcriptome expression from infected and ammonia-treated
      fruit tissue compared with healthy tissue. The analysis revealed 82 and 237
      common upregulated and downregulated genes, respectively. Quantitative reverse
      transcriptase polymerase chain reaction analysis of select transcripts in normal
      and transgenic NADPH oxidase antisense plants revealed that their expression was
      NADPH oxidase dependent. Common-upregulated genes showed overrepresentation of
      salicylic acid (SA)-dependent genes as well as genes related to biotic stress.
      The downregulated genes showed overrepresentation of jasmonic acid (JA)-dependent
      genes. Indeed, direct application of SA to the fruit enhanced C. coccodes
      necrotrophic colonization, whereas the application of JA delayed colonization.
      Importantly, green fruit and red fruit displayed similar gene expression patterns
      although only red fruit is susceptible to colonization. Thus, it is likely that
      the resistance of green fruit to C. coccodes colonization is due to additional
      factors.

PMID- 22150076
TI  - Cancer's unequal impact on incomes in Norway.
AB  - BACKGROUND: At a group level, cancer results in reduced labor earnings. Public
      benefits common to welfare states may, however, compensate for all or parts of
      the decline in earnings. Norwegian cancer survivors' incomes, including both
      labor earnings and compensatory welfare benefits, were compared to those of the
      cancer-free population to assess potential welfare consequences of cancer.
      Possible modifying effects of parental and marital status, education, prior
      earnings and age were assessed in depth. MATERIAL AND METHODS: Log-linear
      regression models were used to estimate incomes across different sociodemographic
      variables using register data covering the entire Norwegian population 40-59
      years old with any income in 2008, 536 600 men and 502 500 women, of whom more
      than 17,000 were diagnosed with cancer in 2000-2007. RESULTS: Compared to the
      cancer-free general population, cancer was associated with a modest 7% decline in
      incomes overall. The decline was, however, significantly associated with
      sociodemographic factors, marital status exempted. Childless men with low
      education and low prior earnings were most adversely affected. Lymphomas and lung
      cancer accounted largely for these unfavorable effects. CONCLUSIONS: Declines in
      earnings after cancer are to a large degree compensated by the Norwegian welfare
      state, and incomes overall are only modestly decreased among cancer survivors
      compared to the general population. Persons with multiple unfavorable
      sociodemographic characteristics experience particularly low incomes after
      cancer. This is of concern in a supposedly egalitarian society with public health
      care and antidiscrimination acts in place. Welfare state interventions, i.e. work
      reintegration efforts and/or compensations for labor earning drops, directed
      specifically towards these subgroups might be warranted.

PMID- 22150077
TI  - Imatinib efficacy by tumor genotype in Korean patients with advanced
      gastrointestinal stromal tumors (GIST): The Korean GIST Study Group (KGSG) study.
AB  - PURPOSE: To assess the efficacy of imatinib for different tumor genotypes in
      Korean patients with advanced gastrointestinal stromal tumors (GIST). MATERIAL
      AND METHODS: Clinical data were collected from 370 consecutive patients with
      locally advanced unresectable, metastatic, or recurrent GIST treated with
      imatinib 400 mg/day between August 2001 and December 2007 at 20 Korean
      institutions. Tumor genotypes were determined for 290 patients by direct DNA
      sequencing of KIT exons 9, 11, 13, and 17, and PDGFRA exons 12, 14, and 18.
      RESULTS: Of 290 patients assessed for genotype, 261 (90.0%) had mutations in KIT:
      222 (76.6%) in exon 11, 35 (12.1%) in exon 9 and two each (0.7%) for exons 13 and
      17. Four patients (1.4%) had mutations in the PDGFRA gene: one in exon 12, and
      three in exon 18. Twenty-five patients (8.6%) had no detectable mutations. The
      best responses of the 235 patients with measurable lesions were: 15 complete
      response (6.4%), 126 partial response (53.5%), 86 stable disease (36.6%), and
      eight progressive disease (3.4%). Patients with KIT exon 9 mutations, compared
      with patients with KIT exon 11 mutations, had a lower objective response rate
      (36.7% vs. 63.6%, p = 0.007) and a shorter progression-free survival (median 28.7
      months vs. 49.4 months, p = 0.001). No statistical difference in overall survival
      was observed between these genotypes. CONCLUSION: This study confirms that
      imatinib efficacy is dependent on genotype in Korean GIST patients, consistent
      with results demonstrated by Western patients with GIST.

PMID- 22150078
TI  - Tumourigenicity and radiation resistance of mesenchymal stem cells.
AB  - BACKGROUND: Cancer stem cells are believed to be more radiation resistant than
      differentiated tumour cells of the same origin. It is not known, however, whether
      normal nontransformed adult stem cells share the same radioresistance as their
      cancerous counterpart. MATERIAL AND METHODS: Nontumourigenic (TERT4) and
      tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell
      line, were grown in culture prior to irradiation and gene expression analysis.
      Radiation resistance was measured using a clonogenic assay. Differences in gene
      expression between the two cell lines, both under nontreated and irradiated
      conditions, were assessed with microarrays (Affymetrix Human Exon 1.0 ST array).
      The cellular functions affected by the altered gene expressions were assessed
      through gene pathway mapping (Ingenuity Pathway Analysis). RESULTS: Based on the
      clonogenic assay the nontumourigenic cell line was found to be more sensitive to
      radiation than the tumourigenic cell line. Using the exon chips, 297 genes were
      found altered between untreated samples of the cell lines whereas only 16 genes
      responded to radiation treatment. Among the genes with altered expression between
      the untreated samples were PLAU, PLAUR, TIMP3, MMP1 and LOX. The pathway analysis
      based on the alteration between the untreated samples indicated cancer and
      connective tissue disorders. CONCLUSION: This study has shown possible common
      genetic events linking tumourigenicity and radiation response. The PLAU and PLAUR
      genes are involved in apoptosis evasion while the genes TIMP3, MMP1 and LOX are
      involved in regulation of the surrounding matrix. The first group may contribute
      to the difference in radiation resistance observed and the latter could be a
      major contributor to the tumourigenic capabilities by degrading the intercellular
      matrix. These results also indicate that cancer stem cells are more radiation
      resistant than stem cells of the same origin.

PMID- 22150079
TI  - Avoiding radical surgery after pre-operative chemoradiotherapy: a possible
      therapeutic option in rectal cancer?
AB  - BACKGROUND: In this modern era of multi-modality treatment there is increasing
      interest in the possibility of avoiding radical surgery in complete responders
      after neo-adjuvant long-course chemoradiotherapy (LCPRT). In this article, we
      present a systematic review of such treatments and discuss their therapeutic
      applicability for the future. METHODS: We searched the PubMed online libraries to
      identify studies that reported on the long-term surgical and pathological
      outcomes after local excision together with those that explored the possibility
      of clinical observation only in patients achieving a complete clinical response
      after LCPRT. RESULTS: Several retrospective (n = 10), one single-arm prospective,
      and one small randomised series have reported on the use of local excision after
      LCPRT and demonstrated acceptably low levels of local recurrence with survival
      comparable to patients progressing to conventional surgery. One prospective
      series allocated patients to observation or radical surgery based on histological
      parameters after local excision (ypT0 and ypT1) and showed no differences in
      outcomes. Two retrospective series from the same group on a Brazilian cohort of
      patients reported excellent long-term outcomes after "wait and watch" in complete
      clinical responders. However, other reports have shown no direct correlation
      between clinical and pathological response. CONCLUSION: Local excision may be an
      appropriate option for selected patients developing good clinical response after
      LCPRT. In our opinion, a policy of clinical observation in complete clinical
      responders after LCPRT may not be a safe strategy, unless we had robust
      predictive models for accurate identification of pathological complete response.
      In order to identify patients that may be potentially appropriate for such an
      approach we propose a clinical algorithm incorporating important clinical,
      radiological, and pathological parameters. The proposed model will require
      validation in a prospective study. Finally, we need randomised data for
      demonstrating the non-inferiority of clinical observation compared to
      conventional surgery before this can be considered as standard possible
      therapeutic option.

PMID- 22150080
TI  - Exploring space in the consultation room: environmental influences during patient
      physician interaction.
AB  - Patients' disclosure of personal information is a key factor in health
      communication. Research shows that the environment can affect self-disclosure.
      The 2 studies reported in this article set out to examine the effects of the
      perceived spaciousness of a consultation room on patient readiness to communicate
      personal information to his or her physician. To influence perceived
      spaciousness, desk size and room size were manipulated. Results from both studies
      show that an increase in room size in particular positively influences perceived
      comfort and intended self-disclosure. However, the affective valence of the
      conversation was found to influence this relation, indicating that people prefer
      a smaller interpersonal distance when the conversation is positively framed and
      room size is large. Furthermore, findings show that spaciousness effects on self
      disclosure are qualified by patient characteristics.

PMID- 22150081
TI  - The AKT1 gene is associated with attention and brain morphology in schizophrenia.
AB  - OBJECTIVES: A meta-analysis of the associations between genetic variants in the
      AKT1 gene and schizophrenia found that a single nucleotide polymorphism (SNP5;
      rs2494732) was associated with schizophrenia in Asian populations. METHODS: In
      this study, we investigated the effects of this SNP on memory and attentional
      performance and brain structure using magnetic resonance imaging in a Japanese
      population (117 patients with schizophrenia and 189 healthy subjects). RESULTS:
      The memory performance, particularly attention/concentration score, measured by
      the Wechsler Memory Scale-Revised in A carriers of SNP5, which was found to be
      enriched in patients with schizophrenia, was lower than that in individuals with
      the G/G genotype. We confirmed the association of the SNP with attentional
      performance using the Continuous Performance Test, which assessed sustained
      attention and vigilance of attentional function. Patients with A allele
      demonstrated lower attentional performance than patients with the G/G genotype.
      Patients with the A allele had smaller gray matter volumes in the right inferior
      parietal lobule related to attentional processes and in the frontostriatal region
      related to different SNPs in AKT1 than patients with the G/G genotype.
      CONCLUSIONS: Our results suggest that a genetic variant of AKT1 might be
      associated with attentional deficits and brain morphological vulnerability in
      patients with schizophrenia.

PMID- 22150082
TI  - Future prospects and challenges of vaccines against filariasis.
AB  - Filarial infections remain a major public health and socio-economic problem
      across the tropics, despite considerable effort to reduce disease burden or
      regionally eliminate the infection with mass drug administration programmes. The
      sustainability of these programmes is now open to question owing to a range of
      issues, not least of which is emerging evidence for drug resistance. Vaccination,
      if developed appropriately, remains the most cost-effective means of long-term
      disease control. The rationale for the feasibility of vaccination against
      filarial parasites including onchocerciasis (river blindness, Onchocerca
      volvulus) and lymphatic filariasis (Wuchereria bancrofti or Brugia malayi) is
      founded on evidence from both humans and animal models for the development of
      protective immunity. Nonetheless, enormous challenges need to be faced in terms
      of overcoming parasite-induced suppression without inducing pathology as well as
      the need to both recognize and tackle evolutionary and ecological obstacles to
      successful vaccine development. Nonetheless, new technological advances in
      addition to systems biology approaches offer hope that optimal immune responses
      can be induced that will prevent infection, disease and/or transmission.

PMID- 22150083
TI  - The effects of laparoscopic Nissen fundoplication on Barrett's esophagus: long
      term results.
AB  - OBJECTIVE: The aim of our study was to conduct a retrospective investigation of
      the efficacy of laparoscopic Nissen fundoplication in patients with Barrett's
      esophagus. MATERIAL AND METHODS: A total of 78 patients with Barrett's esophagus
      underwent surgery. Patients were divided into three groups on the basis of the
      preoperative endoscopic biopsies: a non-intestinal group (n = 63) with fundic or
      cardiac metaplasia, an intestinal group (n = 18) with intestinal metaplasia, and
      a dysplastic group (n = 7) with low-grade dysplasia. Clinical follow-up was
      available in the case of 64 patients at a mean of 42 +/- 16.9 months after
      surgery. RESULTS: Check-up examination revealed total regression of Barrett's
      metaplasia in 10 patients. Partial regression was seen in 9 cases, no further
      progression in 34 patients, and progression into cardiac or intestinal metaplasia
      in 11 patients. No cases of dysplastic or malignant transformation were
      registered. Where we observed the regression of BE, among the postoperative
      functional examinations results of manometry (pressure of lower esophageal
      sphincter) and pH-metry were significantly better compared with those groups
      where no changes occurred in BE, or progression of BE was found. Discussion. Our
      results highlight the importance of the cases of fundic and cardiac metaplasia,
      which can also transform into intestinal metaplasia. CONCLUSIONS: Antireflux
      surgery can appropriately control the reflux disease in a majority of the
      patients who had unsuccessful medical treatment, and it may inhibit the
      progression and induce the regression of Barrett's metaplasia in a significant
      proportion of these patients.

PMID- 22150084
TI  - Adipose-derived stem cells produce factors enhancing peripheral nerve
      regeneration: influence of age and anatomic site of origin.
AB  - Adipose-derived stem cells (ADSCs) are attracting increased attention as a novel
      source in regenerative medicine. Transplantation of ADSCs promotes functional
      recovery in animal models of peripheral nerve injury, but the mechanism of
      enhanced nerve regeneration remains to be elucidated. In addition, it is
      important to examine whether the supportive functions of ADSCs are dependent on
      donor age or anatomic site of origin. In this study, we examined the effects of
      factors produced by mouse ADSCs on Schwann cells (SCs) and dorsal root ganglion
      (DRG) neurons in vitro and compared these effects among ADSCs from donors of
      different age and from different anatomic regions. ADSC-derived soluble factors
      supported survival and proliferation of SCs and promoted neurite outgrowth in DRG
      neurons. These beneficial effects were far superior to that of factors from 3T3
      L1 cells and comparable to those of SC- and astrocyte (AC)-derived factors. ADSCs
      from different sources similarly retained their neurotrophic activity. Real-time
      reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent
      assay analyses demonstrated that ADSCs produced various growth factors, some of
      which were more abundant than in SCs and ACs. These results suggest that ADSCs
      promote peripheral nerve regeneration partly through paracrine secretion of
      trophic factors and regardless of donor age or anatomic site of origin.

PMID- 22150085
TI  - Placental origins of angiogenic dysfunction in mirror syndrome.
AB  - BACKGROUNDL: Mirror syndrome is characterized by preeclampsia-like syndrome in
      pregnancies complicated by fetal hydrops. We describe a case of mirror syndrome
      associated with angiogenic dysfunction in maternal plasma and the placenta. CASE:
      A pregnant patient with known fetal hydrops presented at 22 weeks gestation with
      features of severe preeclampsia. Measurements of plasma anti- and proangiogenic
      factors were consistent with a profound antiangiogenic state.
      Immunohistochemistry of the placenta for antiangiogenic proteins showed a pattern
      similar to that seen in patients with severe preeclampsia. CONCLUSION: Angiogenic
      imbalance may also be responsible for the preeclampsia-like condition seen in
      mirror syndrome.

PMID- 22150086
TI  - Association of protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601
      and Kruppel-like factor 12 (KLF12) rs1324913 single nucleotide polymorphisms with
      rheumatoid arthritis in a Latvian population.

PMID- 22150087
TI  - Expression profile of heat shock proteins in acute myeloid leukaemia patients
      reveals a distinct signature strongly associated with FLT3 mutation status-
      consequences and potentials for pharmacological intervention.
AB  - Heat shock proteins (HSPs) are molecular chaperones that assist proteins in their
      folding to native structures. HSPs are regarded as possible therapeutic targets
      in acute myeloid leukaemia (AML). We used bioinformatical approaches to
      characterize the HSP profile in AML cells from 75 consecutive patients, in
      addition to the effect of the HSP90 inhibitor 17-DMAG. Patients harbouring a FLT3
      internal tandem duplication (FLT3-ITD) were extensively overrepresented in the
      cluster with high HSP levels, indicating a strong dependence of HSPs in
      stabilizing FLT3-ITD encoded oncoproteins. FLT3 ligation further increased the
      levels of HSP90 and its co-chaperone HSP70. HSP90 inhibition had a stronger pro
      apoptotic effect for AML cells with FLT3-ITD than for cells with wild-type FLT3,
      whereas the anti-proliferative effect of HSP90 inhibition was similar for the two
      patient subsets. HSP90 inhibition altered the constitutive cytokine release
      profile in an anti-angiogenic direction independent of FLT3 mutational status:
      (i) pro-angiogenic CXCL8, MMP-2 and MMP-9 showed a stronger decrease than anti
      angiogenic CXCL9-11, (ii) the Tie-2 agonist Ang-1 showed a stronger decrease than
      the potentially antagonistic Ang-2, and (iii) VEGF and HGF levels were decreased.
      Finally, HSP90 inhibition counteracted the leukaemia-stimulating effect of
      endothelial cells. Our studies demonstrate that HSP90 inhibition mediates anti
      leukaemic effects through both direct and indirect activity.

PMID- 22150088
TI  - Supporting patient adherence to antiretrovirals using mobile phone reminders:
      patient responses from South India.
AB  - There has been exponential growth in the use of mobile phones in India over the
      last few years, and their potential benefits as a healthcare tool has raised
      tremendous interest. We used mobile phone reminders to help support adherence to
      antiretroviral therapy (ART) among HIV patients at an infectious disease clinic
      in a tertiary hospital in Bangalore. Between March and June 2010, 139 adult HIV
      patients taking regular ART for at least a month received weekly reminders to
      support adherence. These reminders consisted of a weekly interactive call and a
      non-interactive neutral pictorial short message service (SMS). After four weeks
      of the intervention, participants were interviewed to study perceptions on
      preference, usefulness, potential stigma and privacy concerns associated with
      this intervention. Majority of the participants were urban (89%), and had at
      least a secondary education (85%). A total of 744 calls were made, 545 (76%) of
      which were received by the participants. In addition, all participants received
      the weekly pictorial SMS reminder. A month later, 90% of participants reported
      the intervention as being helpful as medication reminders, and did not feel their
      privacy was intruded. Participants (87%) reported that they preferred the call as
      reminders, just 11% favoured SMS reminders alone. Only 59% of participants viewed
      all the SMSs that were delivered, while 15% never viewed any at all. Participants
      also denied any discomfort or stigma despite 20% and 13%, respectively, reporting
      that another person had inadvertently received their reminder call or SMS. Mobile
      phone interventions are an acceptable way of supporting adherence in this
      setting. Voice calls rather than SMSs alone seem to be preferred as reminders.
      Further research to study the influence of this intervention on adherence and
      health maintenance is warranted.

PMID- 22150090
TI  - Epidemiological shifts in elderly traumatic brain injury: 18-year trends in
      Pennsylvania.
AB  - Older adults tend to have poorer outcomes compared to younger adults following
      moderate-to-severe traumatic brain injury (TBI). Currently, there is a need for
      research focusing on how elderly TBI has changed as the U.S. population shifts.
      This study provides a statewide account of moderate-to-severe TBI in regard to
      injury-related variables and incidence rates in the elderly. Data from
      Pennsylvania accredited trauma centers collected in the Pennsylvania Trauma
      Outcome Study between 1992 and 2009 were used in the current study. Incidence
      rates for TBI were calculated using U.S. Census Bureau estimates for individuals
      aged 65-90 years (separated into three subgroups: ages 65-73, 74-82, and 83-90
      years). In addition, we focused on describing the following injury-related
      variables: mechanism of injury, injury severity, hospital length of stay, and
      functional status at discharge. The results indicate that the incidence of
      elderly TBI has approximately doubled in the past 18 years, and that the increase
      in elderly TBI is greatest for individuals between the ages of 83 and 90.
      Furthermore, this age group had the poorest outcomes following TBI. Prevention
      and awareness of TBI in the elderly is imperative in reducing the likelihood of
      injury and disability. Continued statewide work is needed to demonstrate trends
      in elderly TBI nationwide to further add to the knowledge base used for
      prevention and rehabilitation work.

PMID- 22150091
TI  - Seroprevalence of Toxoplasma gondii in domestic and wild animals from the
      Fernando de Noronha, Brazil.
AB  - Fernando de Noronha is an archipelago of 21 islands and islets in the Atlantic
      Ocean, state of Pernambuco, Brazil, which has a varied biodiversity including
      alien species or sinantropic animals. The objective here was to determine the
      seroprevalence of Toxoplasma gondii in domestic and wild animals from Fernando de
      Noronha archipelago, Brazil. Between July 2007 and May 2010, blood samples were
      collected from 764 animals (533 domestic and 231 wild animals). Sera were tested
      by the indirect fluorescence antibody test (IFAT) or the modified agglutination
      test (MAT), or by both. Antibodies to T. gondii were found in 80 (80.0%) of 100
      chickens ( Gallus domesticus ), 3 (3.0%) of 100 cattle ( Bos taurus ), 59 (60.8%)
      of 97 sheep ( Ovis aries ), 9 (81.8%) of 11 goats ( Capra hircus ), 7 (43.7%) of
      16 horses ( Equus caballus ), 70 (59.3%) of 118 cats ( Felis catus ), 36 (39.6%)
      of 91 dogs ( Canis familiaris ), 13 (38.2%) of 34 black rats ( Rattus rattus ),
      and 157 (79.7%) of 197 cattle egrets ( Bubulcus ibis ). Results indicate endemic
      infection by this zoonotic parasite among the animal and avian fauna in this
      archipelago from Brazil.

PMID- 22150089
TI  - Age-related changes in mechanical properties of the Achilles tendon.
AB  - The stiffness of a tendon, which influences muscular force transfer to the
      skeleton and increases during childhood, is dependent on its material properties
      and dimensions, both of which are influenced by chronic loading. The aims of this
      study were to: (i) determine the independent contributions of body mass, force
      production capabilities and tendon dimensions to tendon stiffness during
      childhood; and (ii) descriptively document age-related changes in tendon
      mechanical properties and dimensions. Achilles tendon mechanical and material
      properties were determined in 52 children (5-12 years) and 19 adults. Tendon
      stiffness and Young's modulus (YM) were calculated as the slopes of the force
      elongation and stress-strain curves, respectively. Relationships between
      stiffness vs. age, mass and force, and between YM vs. age, mass and stress were
      determined by means of polynomial fits and multiple regression analyses. Mass was
      found to be the best predictor of stiffness, whilst stress was best related to YM
      (< 75 and 51% explained variance, respectively). Combined, mass and force
      accounted for up to 78% of stiffness variation. Up to 61% of YM variability could
      be explained using a combination of mass, stress and age. These results
      demonstrate that age-related increases in tendon stiffness are largely
      attributable to increased tendon loading from weight-bearing tasks and increased
      plantarflexor force production, as well as tendon growth. Moreover, our results
      suggest that chronic increases in tendon loading during childhood result in
      microstructural changes which increase the tendon's YM. Regarding the second aim,
      peak stress increased from childhood to adulthood due to greater increases in
      strength than tendon cross-sectional area. Peak strain remained constant as a
      result of parallel increases in tendon length and peak elongation. The
      differences in Achilles tendon properties found between adults and children are
      likely to influence force production, and ultimately movement characteristics,
      which should be explicitly examined in future research.

PMID- 22150092
TI  - Relative importance of different lipid risk factors for the development of
      myocardial infarction at a very young age (<= 40 years of age).
AB  - BACKGROUND: Low-density lipoprotein (LDL) cholesterol lowering has been
      established as one of the principal targets in preventive cardiology. Recently,
      assessment of LDL particle size and number as well as other lipid moieties has
      been presented as a more reliable method to quantify atherogenicity of the
      lipoprotein fractions. Thus, it was our aim to assess the influence of different
      lipoprotein fractions on premature myocardial infarction (<= 40 years of age).
      METHODS AND RESULTS: We enrolled 302 patients into our multicentre case-control
      study, including 102 patients with myocardial infarction and 200 age-, gender-
      and centre-matched controls. The LDL and HDL Lipoprint System were used for lipid
      subfraction quantification. The lipid risk factors most strongly associated with
      premature acute myocardial infarction (AMI) in the adjusted model were non-HDL C
      (OR 5.02, 95% CI 2.75-9.15, P-value = 0.001), LDL-C (OR 4.35, 95% CI 2.5-7.57, P
      value = 0.001), VLDL-C (OR 3.66, 95% CI 2.14-6.28, P-value = 0.001), large IDL-C
      (OR 3.15, 95% CI 1.94-5.12, P-value = 0.001), large LDL-C (OR 3.67, 95% CI 2.19
      6.15, P-value = 0.001) and intermediate LDL-C (OR 1.96, 95% CI 1.25-3.06, P-value
      = 0.003). In contrast, small dense LDL was not significantly associated with
      premature myocardial infarction. CONCLUSION: Non-HDL cholesterol is most strongly
      associated with premature coronary artery disease and could serve as preferred
      risk predictor and therapeutic target in this young patient population (<= 40
      years). Besides, VLDL, LDL-C, large LDL, intermediate LDL and large IDL were
      significantly associated with premature myocardial infarction. Furthermore, our
      data suggest that risk prediction using small dense LDL particles might not be
      useful in young AMI survivors.

PMID- 22150094
TI  - Effect of low-level laser therapy in the treatment of burning mouth syndrome: a
      case series.
AB  - OBJECTIVE: The aim of this study was evaluate the effect of low-level laser
      therapy (LLLT) in the treatment of burning mouth syndrome (BMS) patients.
      BACKGROUND DATA: BMS is a clinical condition characterized by a burning sensation
      in a morphologically normal oral mucosa, without association with systemic
      disorders. METHODS: Ten patients with oral burning sensation were included in the
      study. After careful evaluation of medical history and oral examination, the
      diagnosis of BMS was established. All patients were submitted to one weekly
      session of LLLT for 10 weeks. A continuous wavelength of 660 nm, power 40 mW, 20
      J/cm(2), 0.8 J/point, with each point irradiated for 10 sec. In all sessions the
      burning intensity was evaluated with a 10-cm visual analogue scale (VAS), with 0
      indicating no symptoms and 10 indicating the worst burning possible. The burning
      intensity evaluation by VAS was performed immediately before (VAS baseline) and
      immediately after each LLLT session. The nonparametric Wilcoxon test was used for
      statistical analysis, considering significance of 5%. RESULTS: All patients
      reported improvement in all sessions, with reduction in VAS scores by up to 58%
      in the tenth session. When only the VAS baseline of the first session was
      compared with the other sessions, there was a statistically significant reduction
      in VAS scores in the fourth (p=0.03), fifth (p=0.03), sixth (p=0.009), seventh
      (p=0.003), eighth, ninth, and tenth (all p=0.002) sessions. CONCLUSIONS: LLLT may
      be an alternative treatment for the relief of oral burning in patients with BMS.

PMID- 22150093
TI  - Demethylation of the FCER1G promoter leads to FcepsilonRI overexpression on
      monocytes of patients with atopic dermatitis.
AB  - BACKGROUND: Overexpression of the high-affinity receptor for immunoglobulin E on
      atopic monocytes and dendritic cells is known to contribute to the pathogenesis
      of atopic dermatitis (AD). However, it remains unclear what is the underlying
      mechanism of FcepsilonRI deregulation. It has been speculated that epigenetic
      deregulation may play a role. METHODS: Global DNA methylation levels of monocytes
      from 10 AD patients and 10 healthy controls were measured using a global DNA
      methylation kit. Bisulfite sequencing was performed to determine the methylation
      status of the FCER1G promoter region. FcepsilonRIgamma mRNA and FcepsilonRI
      protein levels were detected by real-time RT-PCR, Western blotting, and flow
      cytometry, respectively. Patch methylation and the demethylating agent, 5
      azacytidine, were used to determine the functional significance of methylation
      changes on FcepsilonRI expression. RESULTS: Monocytes from AD patients show a
      global hypomethylation, as well as a locus-specific hypomethylation at FCER1G
      promoter, as compared to healthy controls. Furthermore, this hypomethylation of
      FCER1G is inversely correlated with its expression. Patch methylation in
      combination with luciferase reporter assay confirmed the direct relationship
      between methylation and expression. Moreover, treating healthy monocytes with 5
      azacytidine caused a reduction in methylation levels and an induction in
      FcepsilonRIgamma transcription and surface expression of FcepsilonRI. CONCLUSION:
      Demethylation of specific regulatory elements within the FCER1G locus contributes
      to FcepsilonRI overexpression on monocytes from patients with AD.

PMID- 22150095
TI  - Shear bond strength of resin cement to zirconia ceramic after aluminum oxide
      sandblasting and various laser treatments.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of different surface
      treatments; sandblasting, Er:YAG, Nd:YAG, or CO(2) laser irradiation on the shear
      bond strength (SBS) of zirconia ceramic to dentin. BACKGROUND DATA: Zirconia is
      not properly luted with resin cements. Various surface treatment methods have
      been suggested for zirconia to obtain high bond strength to resin cements. There
      is no study that compared the effect of different laser types (Er:YAG, Nd:YAG,
      CO(2)) with sandblasting on SBS between zirconia and dentin. METHODS: One hundred
      and twenty human maxillary third molar teeth were sectioned 3 mm below the
      occlusal surfaces, embedded in a metal ring with autopolymerizing acrylic resin,
      and stored in distilled water at 37(0)C. One hundred and twenty disc-shaped
      zirconia specimens were fabricated (6 mm in diameter and 4 mm in thickness), and
      randomly assigned to six groups (n=20): Group 1, untreated (control); Group 2,
      sandblasted; Group 3, Er:YAG laser irradiated; Group 4, Nd:YAG laser irradiated
      with contact; Group 5, Nd:YAG laser irradiated with non-contact; Group 6, CO(2)
      laser irradiated. They were cemented onto the dentin with dual-cured resin cement
      (Variolink((r))). After they were stored in distilled water at 37(0)C for 24 h,
      the SBS test was performed at a crosshead speed of 1 mm/min. The fractured
      specimens were examined under a stereomicroscope to evaluate the fracture
      pattern. RESULTS: Results of this study did not show statistically significant
      differences between Groups 1 and 2, or among Groups 3, 4 and 5. The lowest SBS
      was recorded in Group 6 (CO(2) laser), and the highest SBS was recorded in Group
      4 (Nd:YAG laser with contact), followed by Group 3 (Er:YAG laser). The adhesive
      failure mode was predominantly observed in Groups 2, 3, 5, and 6. Group 1 showed
      45% mixed failure and Group 4 showed 50% mixed failure. CONCLUSIONS: This study
      shows that Er:YAG and Nd:YAG laser treatment increased the bond strength of
      zirconia compared to sandbasting and CO(2) laser treatment.

PMID- 22150096
TI  - Heeding the messages from PREVENT-SCD.

PMID- 22150097
TI  - Divergent evolution of oxidosqualene cyclases in plants.
AB  - Triterpenes are one of the largest classes of plant metabolites and have
      important functions. A diverse array of triterpenoid skeletons are synthesized
      via the isoprenoid pathway by enzymatic cyclization of 2,3-oxidosqualene. The
      genomes of the lower plants Chlamydomonas reinhardtii and moss (Physcomitrella
      patens) contain just one oxidosqualene cyclase (OSC) gene (for sterol
      biosynthesis), whereas the genomes of higher plants contain nine to 16 OSC genes.
      Here we carry out functional analysis of rice OSCs and rigorous phylogenetic
      analysis of 96 OSCs from higher plants, including Arabidopsis thaliana, Oryza
      sativa, Sorghum bicolor and Brachypodium distachyon. The functional analysis
      identified an amino acid sequence for isoarborinol synthase (OsIAS) (encoded by
      Os11g35710/OsOSC11) in rice. Our phylogenetic analysis suggests that expansion of
      OSC members in higher plants has occurred mainly through tandem duplication
      followed by positive selection and diversifying evolution, and consolidated the
      previous suggestion that dicot triterpene synthases have been derived from an
      ancestral lanosterol synthase instead of directly from their cycloartenol
      synthases. The phylogenetic trees are consistent with the reaction mechanisms of
      the protosteryl and dammarenyl cations which parent a wide variety of triterpene
      skeletal types, allowing us to predict the functions of the uncharacterized OSCs.

PMID- 22150098
TI  - Red versus white wine as a nutritional aromatase inhibitor in premenopausal
      women: a pilot study.
AB  - BACKGROUND: An increased risk of breast cancer is associated with alcohol
      consumption; however, it is controversial whether red wine increases this risk.
      Aromatase inhibitors (AIs) prevent the conversion of androgens to estrogen and
      occur naturally in grapes, grape juice, and red, but not white wine. We tested
      whether red wine is a nutritional AI in premenopausal women. METHODS: In a cross
      over design, 36 women (mean age [SD], 36 [8] years) were assigned to 8 ounces
      (237 mL) of red wine daily then white wine for 1 month each, or the reverse.
      Blood was collected twice during the menstrual cycle for measurement of estradiol
      (E2), estrone (E1), androstenedione (A), total and free testosterone (T), sex
      hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle
      stimulating hormone (FSH). RESULTS: Red wine demonstrated higher free T vs. white
      wine (mean difference 0.64 pg/mL [0.2 SE], p=0.009) and lower SHBG (mean
      difference -5.0 nmol/L [1.9 SE], p=0.007). E2 levels were lower in red vs. white
      wine but not statistically significant. LH was significantly higher in red vs.
      white wine (mean difference 2.3 mIU/mL [1.3 SE], p=0.027); however, FSH was not.
      CONCLUSION: Red wine is associated with significantly higher free T and lower
      SHBG levels, as well as a significant higher LH level vs. white wine in healthy
      premenopausal women. These data suggest that red wine is a nutritional AI and may
      explain the observation that red wine does not appear to increase breast cancer
      risk.

PMID- 22150099
TI  - Patient-centered care: the influence of patient and resident physician gender and
      gender concordance in primary care.
AB  - BACKGROUND: Patient-centered care (PCC) is thought to significantly influence the
      process of care and its outcomes and has been identified as part of a
      comprehensive strategy for improving our nation's healthcare delivery system.
      Patient and physician gender, as well as gender concordance, may influence the
      provision of PCC. METHODS: Patients (315 women, 194 men) were randomized to care
      by primary care resident physicians (48 women, 57 men). Sociodemographic
      information, history of health risk behaviors (tobacco use, alcoholism, and
      obesity), and self-reported global pain and health status were collected before
      the first visit. That visit and subsequent patient visits to the primary care
      physician (PCP) were videotaped during the year-long study period. PCC was
      measured by coding all videotapes using a modified version of the Davis
      Observation Code. RESULTS: No significant gender differences in PCC were found
      between the male and female patients; however, female physicians provided
      increased PCC to their patients. The greatest amount of PCC was seen in the
      female patient-female physician gender dyad. Regression analyses, controlling for
      other patient variables, confirmed that female concordant dyads were associated
      with a greater amount of PCC. There was no significant relationship for the male
      patient-male physician concordance (vs. disconcordance). CONCLUSIONS: These
      findings highlight the influence of gender in the process of care and provision
      of PCC. Gender concordance in female patient-female physician dyads demonstrated
      significantly more PCC. Further research in other clinical settings using other
      measures of PCC is needed. A public mandate to provide care that is patient
      centered has implications for medical education.

PMID- 22150102
TI  - Hidden in plain sight: catatonia in pediatrics: "An editorial comment to Shorter
      E. "Making childhood catatonia visible (Separate from competing diagnoses", (1)
      Dhossche D, Ross CA, Stoppelbein L. 'The role of deprivation, abuse, and trauma
      in pediatric catatonia without a clear medical cause', (2) Ghaziuddin N, Dhossche
      D, Marcotte K. 'Retrospective chart review of catatonia in child and adolescent
      psychiatric patients' (3)".

PMID- 22150101
TI  - Making childhood catatonia visible, separate from competing diagnoses.

PMID- 22150103
TI  - The dimension of psychotic experiences: an editorial comment to Ahmed A, Buckley
      P, Mabe A. 'Latent structure of psychotic experiences in the general population'
      (3).

PMID- 22150106
TI  - Docking and QSAR comparative studies of polycyclic aromatic hydrocarbons and
      other procarcinogen interactions with cytochromes P450 1A1 and 1B1.
AB  - To obtain chemical clues on the process of bioactivation by cytochromes P450 1A1
      and 1B1, some QSAR studies were carried out based on cellular experiments of the
      metabolic activation of polycyclic aromatic hydrocarbons and heterocyclic
      aromatic compounds by those enzymes. Firstly, the 3D structures of cytochromes
      1A1 and 1B1 were built using homology modelling with a cytochrome 1A2 template.
      Using these structures, 32 ligands including heterocyclic aromatic compounds,
      polycyclic aromatic hydrocarbons and corresponding diols, were docked with
      LigandFit and CDOCKER algorithms. Binding mode analysis highlighted the
      importance of hydrophobic interactions and the hydrogen bonding network between
      cytochrome amino acids and docked molecules. Finally, for each enzyme,
      multilinear regression and artificial neural network QSAR models were developed
      and compared. These statistical models highlighted the importance of electronic,
      structural and energetic descriptors in metabolic activation process, and could
      be used for virtual screening of ligand databases. In the case of P450 1A1, the
      best model was obtained with artificial neural network analysis and gave an r (2)
      of 0.66 and an external prediction [Formula: see text] of 0.73. Concerning P450
      1B1, artificial neural network analysis gave a much more robust model, associated
      with an r (2) value of 0.73 and an external prediction [Formula: see text] of
      0.59.

PMID- 22150107
TI  - Adipoparacrinology--vascular periadventitial adipose tissue (tunica adiposa) as
      an example.
AB  - Human adipose tissue is partitioned into two large depots (subcutaneous and
      visceral), and many small depots associated with internal organs, e.g. heart,
      blood vessels, major lymph nodes, pancreas, prostate gland and ovaries. Since the
      adipose 'Big Bang' led to the discovery of leptin (Zhang, Proenca, Maffei,
      Barone, Leopold and Friedman, Nature 1994;372:425-32), adipose tissue has been
      seen not merely as a lipid store, but as a secretory - endocrine and paracrine -
      organ, particularly in the pathogenesis of a number of diseases. Accordingly, two
      major sub-fields of adipobiology have emerged, viz. adipoendocrinology and
      adipoparacrinology, the latter herein being illustrated by PAAT (periadventitial
      adipose tissue) in vascular walls. A long-standing paradigm holds that the
      vascular wall consists of three coats, tunica intima, tunica media and tunica
      adventitia. It is now imperative that 'to further elucidate vascular function, we
      should no longer, as hitherto, separate adventitia and PAAT from the vascular
      wall, but keep them attached and in place, and subject to thorough examination'
      (Chaldakov, Fiore, Ghenev, Stankulov and Aloe, Int Med J 2000;7:43-9; Chaldakov,
      Stankulov and Aloe, Atherosclerosis 2001;154:237-8; Chaldakov GN, Stankulov IS,
      Fiore M, Ghenev PI and Aloe L, Atherosclerosis 2001;159:57-66). From the
      available data, we propose that it is time to rethink about vascular wall
      composition, and suggest that the PAAT may be considered the fourth and outermost
      vascular coat, hence, tunica adiposa (regarding the proximal segment of coronary
      artery, it is the innermost part of the EAT (epicardial adipose tissue) situated
      around the coronary adventitia). Its significance in the pathogenesis and therapy
      of CMDs (cardiometabolic diseases), particularly atherosclerosis and
      hypertension, requires further basic, translational and clinical studies.

PMID- 22150108
TI  - Widespread roles of microRNAs during zebrafish development and beyond.
AB  - MicroRNAs (miRNAs) are a class of small RNAs that are approximately 22
      nucleotides in length. Hundreds of miRNA genes are encoded in the animal genome,
      and each miRNA potentially regulates tens to hundreds of protein-coding
      transcripts post-transcriptionally. Experimental and bioinformatic approaches
      have shown widespread regulatory roles for miRNAs in metazoa including roles in
      cellular homeostasis and human diseases. Since the discoveries of let-7 and lin-4
      miRNAs as regulators of developmental timing in Caenorhabditis elegans, functions
      of miRNAs in the context of animal development have been studied in many model
      organisms. Although miRNAs are essential to achieve complex developmental
      processes, the vast majority of animal miRNA functions have yet to be determined.
      The identification of miRNA-target interactions and the interpretation of their
      biological significance are often difficult due to the divergent functions of
      miRNAs in intricate gene regulatory networks. This review summarizes our current
      knowledge on miRNA functions in vertebrate development by focusing on the
      progress made in the vertebrate model organism zebrafish (Danio rerio). Studies
      of miRNA functions in this small teleost highlight several common principles
      underlying the functions of animal miRNAs.

PMID- 22150109
TI  - Analyzing Brazilian vehicle documents for authenticity by easy ambient sonic
      spray ionization mass spectrometry.
AB  - Using desorption/ionization techniques such as easy ambient sonic-spray
      ionization mass spectrometry (EASI-MS), it is possible to analyze documents of
      Brazilian vehicles for authenticity, providing a chemical profile directly from
      the surface of each document. A method for the detection of counterfeit documents
      is described, and the falsification procedure is elucidated. Forty authentic and
      counterfeit documents were analyzed by both positive and negative ion modes,
      EASI(+/-)-MS. EASI(+)-MS results identified the presence of (bis(2
      ethylhexyl)phthalate plasticizer and of dihexadecyldimethylammonium biocide in
      both types of documents. For EASI(-)-MS results, the 4-octyloxybenzoic acid
      additive ([M + H](+): m/z 249) is present only in counterfeit documents. It was
      also found that counterfeit vehicle documents are produced via Laserjet printers.
      Desorption/ionization techniques, such as EASI-MS, offer therefore, an
      intelligent way to characterize the counterfeiting method.

PMID- 22150110
TI  - The influence of osteoblast differentiation stage on bone formation in
      autogenously implanted cell-based poly(lactide-co-glycolide) and calcium
      phosphate constructs.
AB  - We tested the hypothesis that the osteoblast differentiation status of bone
      marrow stem cells (BMSCs) combined with a three-dimensional (3D) structure
      modulates bone formation when autogenously implanted. Rat BMSCs were aspirated,
      expanded, and seeded into a 3D composite of poly(lactide-co-glycolide) and
      calcium phosphate (PLGA/CaP) to produce a hybrid biomaterial. Calvarial defects
      were implanted with (1) scaffold without cells (SC/NC), (2) scaffold and BMSCs
      (SC+BMSC), (3) scaffold and osteoblasts differentiated for 7 days (SC+OB7), and
      (4) for 14 days (SC+OB14). After 4 weeks, there was more bone formation in groups
      combining scaffold and cells, SC+BMSC and SC+OB7. A nonsignificant higher amount
      of bone formation was observed on SC+OB14 compared with SC/NC. Additionally, more
      blood vessels were counted within all hybrid biomaterials, without differences
      among them, than into SC/NC. These findings provide evidences that the cell
      differentiation status affects in vivo bone formation in autogenously implanted
      cell-based constructs. Undifferentiated BMSCs or osteoblasts in early stage of
      differentiation combined with PLGA/CaP scaffold favored bone formation compared
      with plain scaffold and that one associated with more mature osteoblasts.

PMID- 22150112
TI  - The declaration of Helsinki and post-study access to effective drug treatments
      for subjects participating in clinical trials.

PMID- 22150111
TI  - Selective reduction of hydroperoxyeicosatetraenoic acids to their hydroxy
      derivatives by apolipoprotein D: implications for lipid antioxidant activity and
      Alzheimer's disease.
AB  - ApoD (apolipoprotein D) is up-regulated in AD (Alzheimer's disease) and upon
      oxidative stress. ApoD inhibits brain lipid peroxidation in vivo, but the
      mechanism is unknown. Specific methionine residues may inhibit lipid peroxidation
      by reducing radical-propagating L-OOHs (lipid hydroperoxides) to non-reactive
      hydroxides via a reaction that generates MetSO (methionine sulfoxide). Since apoD
      has three conserved methionine residues (Met(49), Met(93) and Met(157)), we
      generated recombinant proteins with either one or all methionine residues
      replaced by alanine and assessed their capacity to reduce HpETEs
      (hydroperoxyeicosatetraenoic acids) to their HETE (hydroxyeicosatetraenoic acid)
      derivatives. ApoD, apoD(M49-A) and apoD(M157-A) all catalysed the reduction of
      HpETEs to their corresponding HETEs. Amino acid analysis of HpETE-treated apoD
      revealed a loss of one third of the methionine residues accompanied by the
      formation of MetSO. Additional studies using apoD(M93-A) indicated that Met(93)
      was required for HpETE reduction. We also assessed the impact that apoD MetSO
      formation has on protein aggregation by Western blotting of HpETE-treated apoD
      and human brain samples. ApoD methionine oxidation was associated with formation
      of apoD aggregates that were also detected in the hippocampus of AD patients. In
      conclusion, conversion of HpETE into HETE is mediated by apoD Met(93), a process
      that may contribute to apoD antioxidant function.

PMID- 22150113
TI  - Blind spots and adverse conditions of care: screening migrants for tuberculosis
      in France and Germany.
AB  - Tuberculosis (TB) is an infectious disease that declined significantly throughout
      the 20(th)  century. Large-scale TB screening of entire populations in France and
      Germany has thus been replaced by active screening of risk-groups, particularly
      migrants. The article engages with its problems and practices on three levels: by
      looking at the way information on migrants as an at-risk group is produced
      through disease surveillance data; by analysing how such at-risk group data
      influence local screening practices; and by showing which political and medical
      problems arise in the field. I overturn the discussion about screening and
      surveillance of migrants as a risk-group by showing that it is not the
      stigmatisation of migrants through disease risk that is most at stake, but the
      invisibility of the most vulnerable among them in disease surveillance data and
      the way restrictive national immigration policies interfere with and subvert
      local screening and treatment practices targeting them. The aim of my article is
      to promote a pragmatic sociology of screening, while paying attention to the
      practical complexities, political conditions and medical ambivalences of
      screening and follow-up care, especially when the migrant groups concerned are
      socially, politically and medically vulnerable.

PMID- 22150114
TI  - Cancer and "playing" with reality: clinical guidance with the help of the
      intermediate area and disavowal.

PMID- 22150115
TI  - Submandibular gland-sparing intensity modulated radiotherapy in the treatment of
      head and neck cancer: sites of locoregional relapse and survival.
AB  - BACKGROUND AND PURPOSE: To evaluate the patterns of locoregional relapse and
      survival following submandibular gland (SMG)-sparing intensity modulated
      radiotherapy (IMRT). PATIENTS AND METHODS: Eighty patients with laryngeal (n =
      15), oropharyngeal (n = 50), hypopharyngeal (n = 11) or nasopharyngeal cancer (n
      = 4) were treated by submandibular gland-sparing IMRT for head and neck squamous
      cell cancer between July 2000 and December 2008. All patients were treated by
      bilateral IMRT. Thirty-nine (49%) received definitive radiotherapy (RT) and 41
      (51%) postoperative RT. The contralateral parotid gland (PG) and SMG were
      included in the dose optimization planning program with intent to keep the mean
      doses for PG and SMG below 23 Gy and 28-30 Gy, respectively. The ipsilateral
      glands were also spared when considered feasible. RESULTS: During a median follow
      up time of 51 months (range, 24-117 months) nine local recurrent tumors were
      observed. Four of these nine patients were salvaged by surgery with no further
      recurrence. All local recurrences were located within the high-dose CTVs. None of
      the locally recurrent cancers were located at the vicinity of the spared PGs or
      SMGs. No recurrent tumors were observed in the contralateral neck. The Kaplan
      Meier estimate for local control at five years following IMRT was 88% for the
      whole cohort and the corresponding figure for local control following salvage
      surgery was 94%. The estimates for five-year overall survival and disease
      specific survival were 85% and 90%, respectively. CONCLUSION: In selected head
      and neck cancer patients who are estimated to have a low risk of cancer
      recurrence at the nodal levels I-II and who are treated with SMG-sparing IMRT the
      risk of cancer recurrence at the vicinity of the spared salivary glands is low.

PMID- 22150116
TI  - Denosumab and the current status of bone-modifying drugs in breast cancer.
AB  - BACKGROUND: Bone-modifying therapy is a primary research interest in breast
      cancer. Several features contribute to the importance of the bone environment in
      the management of breast cancer. Firstly, bone metastases represent the most
      common site of breast cancer metastases and secondly, the emergence of cancer
      treatment-induced bone loss (CTIBL) among breast cancer survivors and patients is
      of increasing concern. Furthermore, concordant with the "seed and soil" theory,
      agents that alter the bone microenvironment may even prevent tumor cell seeding
      in bone and limit cancer growth. MATERIAL AND METHODS: Medical databases and
      conference proceedings were searched to identify articles, abstracts and clinical
      trials that have or are investigating denosumab and bisphosphonates in cancer
      therapy. Our search included a predefined focus on bone-modifying therapies in
      early and advanced breast cancer. RESULTS AND DISCUSSION: Bisphosphonates (BPs)
      have an established role both in the prevention and treatment of CTIBL and have
      been studied in the adjuvant setting for early breast cancer (EBC). Denosumab is
      a monoclonal antibody directed against RANK ligand and thereby inhibits
      osteoclastogenesis and bone resportion. It is the newest agent approved for the
      treatment of postmenopausal osteoporosis and the prevention of skeletal-related
      events (SRE) in cancer patients with solid tumors and bone metastases. Denosumab
      has a favorable toxicity profile in comparison to BPs and has the potential to
      improve cancer outcomes. CONCLUSION: This review examines the existing role of
      denosumab in the treatment of bone complications of breast cancer and its
      potential role as adjuvant therapy.

PMID- 22150117
TI  - Severe dermatologic adverse reactions after exposure to lenalidomide in multiple
      myeloma patients with a positive HLA-DRB1*1501 and HLA-DQB1*0602.

PMID- 22150118
TI  - A curated database of genetic markers from the angiogenesis/VEGF pathway and
      their relation to clinical outcome in human cancers.
AB  - INTRODUCTION: Angiogenesis causes local growth, aggressiveness and metastasis in
      solid tumors, and thus, is almost always associated with poor prognosis and
      survival in cancer patients. Because of this clinical importance, several
      chemotherapeutic agents targeting angiogenesis have also been developed. Genes
      and genetic variations in angiogenesis/VEGF pathway thus may be correlated with
      clinical outcome in cancer patients. MATERIAL AND METHODS: Here, we describe a
      manually curated public database, dbANGIO, which posts the results of studies
      testing the possible correlation of genetic variations (polymorphisms and
      mutations) from the angiogenesis/VEGF pathway with demographic features,
      clinicopathological features, treatment response and toxicity, and prognosis and
      survival-related endpoints in human cancers. The scientific findings are
      retrieved from PUBMED and posted in the dbANGIO website in a summarized form.
      RESULTS AND CONCLUSION: As of September 2011, dbANGIO includes 362 entries from
      83 research articles encompassing 154 unique genetic variations from 39 genes
      investigated in several solid and hematological cancers. By curating the
      literature findings and making them freely available to researchers, dbANGIO will
      expedite the research on genetic factors from the angiogenesis pathway and will
      assist in their utility in clinical management of cancer patients. dbANGIO is
      freely available for non-profit institutions at http://www.med.mun.ca/angio.

PMID- 22150119
TI  - Social determinants, lived experiences, and consequences of household food
      insecurity among persons living with HIV/AIDS on the shore of Lake Victoria,
      Kenya.
AB  - Food insecurity is a considerable challenge in sub-Saharan Africa,
      disproportionately affecting persons living with HIV/AIDS. This study
      investigates the lived experience, determinants, and consequences of food
      insecurity and hunger among individuals living with HIV/AIDS on the shore of Lake
      Victoria in Suba District, Kenya. Parallel mixed methods included semi-structured
      interviews and administration of the Household Food Insecurity Access Scale among
      a systematic sample of 67 persons living with HIV/AIDS (49 of whom were receiving
      antiretroviral therapy [ART]). All respondents were either severely (79.1%) or
      moderately (20.9%) food insecure; no respondents were mildly food insecure or
      food secure. Qualitative data and simple and multiple linear regression models
      indicated that significant determinants of food insecurity include increased age,
      a greater number of children, and not being married. A number of themes related
      to food insecurity and ART emerged, including: (1) an increase in hunger or
      appetite since initiating ART; (2) exacerbation of ART-related side effects; and
      (3) non-adherence to ART due to hunger, food insecurity, or agricultural work
      responsibilities. HIV interventions should address food insecurity and hunger,
      particularly among at-risk populations, to promote ART adherence and better
      health outcomes.

PMID- 22150120
TI  - Globalization of health care delivery in the United States through medical
      tourism.
AB  - This study highlights some of the inefficiencies in the U.S. health care system
      and determines what effect medical tourism has had on the U.S. and global health
      care supply chains. This study also calls attention to insufficient health
      communication efforts to inform uninsured or underinsured medical tourists about
      the benefits and risks and determines the managerial and cost implications of
      various surgical procedures on the global health care system into the future.
      This study evaluated 3 years (2005, 2007, and 2011) of actual and projected
      surgical cost data. The authors selected 3 countries for analysis: the United
      States, India, and Thailand. The surgeries chosen for evaluation were total knee
      replacement (knee arthroplasty), hip replacement (hip arthroplasty), and heart
      bypass (coronary artery bypass graft). Comparisons of costs were made using Monte
      Carlo simulation with variability encapsulated by triangular distributions. The
      results are staggering. In 2005, the amount of money lost to India and Thailand
      on just these 3 surgeries because of cost inefficiencies in the U.S. health care
      system was between 1.3 to 2 billion dollars. In 2011, because many more Americans
      are expected to travel overseas for health care, this amount is anticipated to
      rise to between 20 and 30.2 billion dollars. Therefore, more attention should be
      paid to health communication efforts that truly illustrate the benefits/risks of
      medical travel. The challenge of finding reliable data for surgeries performed
      and associated surgical cost estimates was mitigated by the use of a Monte Carlo
      simulation of triangular distributions. The implications from this study are
      clear: If the U.S. health care industry is unable to eliminate waste and
      inefficiency and thus curb rising costs, it will continue to lose surgical
      revenue to foreign health providers.

PMID- 22150121
TI  - Endoscopic treatment of anastomotic biliary complications after liver
      transplantation using removable, covered, self-expandable metallic stents.
AB  - OBJECTIVE: Anastomotic bile duct complications after liver transplantation (LT)
      have been treated endoscopically by dilation and plastic tube stenting, with the
      stent therapy having moved toward using covered, self-expandable metallic stents
      (cSEMS) in recent years. The aim of this study was to analyze therapy outcome of
      post-LT anastomotic complications using cSEMS. MATERIAL AND METHODS: Seventeen
      post-LT patients had 29 cSEMS (Allium stent, n = 23; Wallstent, n = 4; Micro
      Tech, n = 2) placed during endoscopic retrograde cholangiopancreatography (ERCP).
      The fully covered stents (Allium, Micro-Tech) were placed entirely inside the
      common bile duct. Data were collected and analyzed in a retrospective manner.
      RESULTS: These 17 patients had 19 stent treatment periods. Resolution was
      eventually established in all patients. There were four (14%) stent migrations.
      Pancreatitis was seen after one ERCP procedure, whereas five cases of cholangitis
      were seen. CONCLUSION: Treatment of post-LT anastomotic complications with cSEMS
      seems to be both safe and efficient. Further assessment regarding indications,
      stent types and stenting time is needed.

PMID- 22150122
TI  - Expression of human leukocyte antigen-G during normal placentation and in
      preeclamptic pregnancies.
AB  - OBJECTIVES: This study was undertaken to investigate the expression pattern of
      human leukocyte antigen-G (HLA-G) during normal placentation and determine
      whether altered expression of HLA-G is associated with severe preeclampsia.
      METHODS: We investigated HLA-G protein levels in first (n = 27), second (n = 7),
      and third trimester placentas (n = 10) from normal pregnancies, and determined
      HLA-G levels in term placentas from normal (n = 15) and severe preeclamptic
      pregnancies (n = 14) using real-time RT-PCR and western blot analysis. RESULTS:
      In normal placentas, HLA-G protein expression reached a peak level at gestational
      weeks 6 and 7, then gradually decreased from week 8 to third trimester (p <
      0.05). In preeclamptic placentas, both HLA-G mRNA and protein levels were
      decreased significantly in comparison with normal term placentas (p < 0.05).
      CONCLUSION: HLA-G may contribute to placentation during early and mid-term
      pregnancy, and participate in maintaining gestation during term pregnancy. The
      reduced level of HLA-G may be associated with pathogenesis of preeclampsia.

PMID- 22150123
TI  - Inorganic phosphate and FGF-23 predict outcome in stable systolic heart failure.
AB  - BACKGROUND: Recent studies show associations between inorganic phosphate and risk
      of heart failure in the general population as well as between fibroblast growth
      factor 23 (FGF-23) and outcome in coronary heart disease. This study was carried
      out to assess whether circulating levels of inorganic phosphate and FGF-23, a new
      central hormone in mineral bone metabolism, predict outcome in systolic heart
      failure. MATERIALS AND METHODS: Ninety-nine consecutive outpatients with systolic
      heart failure were enrolled. Mean (SD) age was 61 years (11), mean left
      ventricular ejection fraction (LVEF) was 33% (10), 82 patients were men, median
      estimated creatinine clearance was 83 mL/min (Q(1) -Q(3) 58-106), median NTproBNP
      level was 803 pg/mL (Q(1) -Q(3) 404-2757), median inorganic phosphate was 1.12 mM
      (Q(1) -Q(3) 1.02-1.22), median FGF-23 was 39.02 pg/mL (Q(1) -Q(3) 32.45-55.86)
      and median follow-up was 35 months. Associations between inorganic phosphate, FGF
      23 and endpoints were assessed using Cox regression analyses. RESULTS: Inorganic
      phosphate and FGF-23 levels were significantly higher (P < 0.001 and P = 0.009)
      in patients reaching the combined endpoint of cardiac hospitalization or death.
      FGF-23 (ln) predicted all-cause mortality (hazard ratio (HR) 5.042, P = 0.032) in
      a model adjusted for age, gender, estimated creatinine clearance, LVEF, New York
      Heart Association (NYHA) stage and NTproBNP level. Inorganic phosphate predicted
      heart failure hospitalization (HR 26.944, P = 0.021), cardiac hospitalization (HR
      16.016, P = 0.017) and the combined endpoint (HR 13.294, P = 0.015) in models
      adjusted for the same co-variables. CONCLUSION: The results of this study
      demonstrate the independent prognostic value of inorganic phosphate and FGF-23 in
      heart failure even in the context of established risk markers.

PMID- 22150124
TI  - Behind the scenes of non-nodal MCL: downmodulation of genes involved in actin
      cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53
      pathway and mutated status of immunoglobulin heavy chain genes.
AB  - Mantle cell lymphoma (MCL) is an aggressive neoplasm with a short survival. Cases
      with leukaemic MCL and splenomegaly without adenopathies (non-nodal MCL) may have
      a more indolent course. To gain insights into the biological features underlying
      this presentation, we investigated the gene expression profile (GEP) and the IGHV
      mutational status in a cohort of leukaemic MCL cases. Comparison of MCL with
      other lymphoproliferative disorders (i.e. splenic marginal zone lymphoma,
      follicular lymphoma, chronic lymphocytic leukaemia) revealed a MCL signature
      enriched for the following gene categories: mitochondrion, oxidoreductase
      activity, response to stress, to DNA damage and TP53-pathway. Furthermore, GEP
      analysis revealed that non-nodal MCL cases were characterized by the down
      modulation of the following gene categories: cell projection, actin cytoskeleton
      organization, cell adhesion (ITGAE, CELSR1, PCDH9) and tumour
      invasion/progression (PGF, ST14, ETS1, OCIAD1, EZR). Many down-modulated genes
      were related to the TP53-pathway and to DNA damage response. IGHV status proved
      unmutated in all nodal and mutated in all non-nodal MCL. Non-nodal leukaemic MCLs
      display a peculiar clinical presentation, with distinctive biological features,
      such as mutated IGHV and a transcriptional profile lacking tumour invasion
      properties, that might contribute to the absence of nodal involvement and to the
      less aggressive clinical course.

PMID- 22150125
TI  - The impact of atrial fibrillation ablation on left atrial function: association
      with baseline left atrial function.
AB  - BACKGROUND: The effect of atrial fibrillation (AF) ablation on left atrial (LA)
      function has not been sufficiently determined. METHODS: We enrolled 115
      consecutive patients with paroxysmal or persistent AF that underwent AF ablation.
      Multidetector computed tomography was performed in sinus rhythm before and 3
      months after ablation to evaluate LA volume (LAV) and function. Estimates of
      maximum and minimum LAV were used to calculate LA emptying fraction (LAEF)
      ([maximum-minimum LAV]/maximum LAV * 100). RESULTS: AF ablation significantly
      decreased maximum LAV (59.0 +/- 20.4 to 53.3 +/- 16.7 cm(3) , P = 0.001), and
      maintained LAEF (44.5 +/- 13.1% to 43.7 +/- 10.9%, P = 0.49). The larger the
      baseline maximum LAV, the greater the decrease in LAV after ablation, and a
      smaller baseline LAEF was associated with a larger recovery of LAEF after
      ablation (regression coefficient =-0.45 and -0.56, respectively, P < 0.0001).
      Multivariable analyses revealed that an impaired baseline LAEF was an independent
      predictor of an improvement in LA function (an increase in LAEF of >10%; odds
      ratio [OR] = 0.88, P < 0.0001), while an older age and preserved baseline LAEF
      were independently associated with a deterioration of LA function (a decrease in
      LAEF of >10%; OR = 1.06, P = 0.03; and OR = 1.10, P = 0.0001). CONCLUSIONS: AF
      ablation appears to have a beneficial effect on LA function in patients with
      impaired LA function at baseline. However, it may reduce LA function in patients
      with an older age and preserved baseline LAEF.

PMID- 22150126
TI  - Sublingual allergen immunotherapy: mode of action and its relationship with the
      safety profile.
AB  - Allergen immunotherapy reorients inappropriate immune responses in allergic
      patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in
      the European Union, as an effective alternative to subcutaneous allergen
      immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has
      a better safety profile. This is possibly because oral antigen-presenting cells
      (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype,
      despite constant exposure to danger signals from food and microbes. This reduces
      the induction of pro-inflammatory immune responses leading to systemic allergic
      reactions. Oral tissues contain relatively few mast cells and eosinophils (mostly
      located in submucosal areas) and, in comparison with subcutaneous tissue, are
      less likely to give rise to anaphylactic reactions. SLIT-associated immune
      responses include the induction of circulating, allergen-specific Th1 and
      regulatory CD4+ T cells, leading to clinical tolerance. Although 40-75% of
      patients receiving SLIT experience mild, transient local reactions in the oral
      mucosa, these primary reactions rarely necessitate dose reduction or treatment
      interruption. We discuss 11 published case reports of anaphylaxis (all nonfatal)
      diagnosed according to the World Allergy Organization criteria and relate this
      figure to the approximately 1 billion SLIT doses administered worldwide since
      2000. Anaphylaxis risk factors associated with SCIT and/or SLIT should be
      characterized further.

PMID- 22150127
TI  - Organizational breakthrough in addictions during 2011.

PMID- 22150128
TI  - Alcohol use among Asian American adolescent girls: the impact of immigrant
      generation status and family relationships.
AB  - Underage drinking among Asian American adolescent girls is not well understood.
      Based on family interaction theory, the study examined the interrelationships
      among acculturation variables, family relationships, girls' depressed mood, peer
      alcohol use, and girls' alcohol use in a sample of 130 Asian American mother
      daughter dyads. The mediating role of family relationships, girls' depressed
      mood, and peer alcohol use on girls' drinking was also assessed. The study
      advances knowledge related to alcohol use among early Asian American adolescent
      girls, highlights the effect of immigrant generation status and family
      relationships, and has implications for culturally specific underage drinking
      prevention programs.

PMID- 22150130
TI  - Cultural protective factors for community risks and substance use among rural
      African American adolescents.
AB  - Relatively little attention has been afforded to protective factors for community
      level risks among non-urban populations. This study examined the extent to which
      traditional cultural attitudes and behaviors of 137 African American adolescents
      (ages 12-17) from a rural community moderated the relationship between perceived
      community disorganization and substance use behaviors. Results from hierarchical
      linear regression revealed that traditional cultural attitudes and behaviors were
      differentially related to community disorganization and adolescent substance use.
      In terms of protective influences, religious beliefs and practices and
      traditional family practices moderated the effect of community disorganization on
      substance use. Specifically, religious beliefs and practices demonstrated a
      protective-stabilizing effect as community disorganization increased; traditional
      family practices demonstrated a protective but reactive effect. Attitudes of
      cultural mistrust increased youth's susceptibility to substance use as community
      disorganization worsened--vulnerable and reactive. The findings underscore the
      importance of examining the link between cultural and contextual factors in an
      attempt to understand the etiology of substance use among rural African American
      adolescents.

PMID- 22150129
TI  - An exploratory model of substance use among Asian American women: the role of
      depression, coping, peer use and Asian values.
AB  - This study explored the relationship among Asian values, depressive symptoms,
      perceived peer substance use, coping strategies, and substance use among 167
      Asian American college women. More than 66% of the women in our sample scored
      higher than the clinical cutoff score on the Center of Epidemiological Depression
      Scale. Three path analyses examining illicit drugs, alcohol use, and binge
      drinking indicated that perceived peer use was the most robust predictor of
      substance use. Depressive symptoms were positively associated with illicit drug
      use and alcohol consumption but were not related to binge drinking. Asian values
      and coping strategies were not predictive of substance use. Additional analysis
      revealed that avoidant coping was a strong predictor of depressive symptoms.

PMID- 22150131
TI  - Beliefs of older Mexican American women about alcohol and alcohol use.
AB  - This exploratory study assessed the belief system regarding alcohol use in a non
      clinical population of Mexican American women age 55 and older drawn from a
      potential population of 1,000 older adults who attend nine senior centers. The
      overriding research question was: What are the normative attitudes, knowledge,
      and behavior regarding alcohol in this population of older Mexican American
      women? Findings from this study can serve as a baseline for comparison for future
      studies of older Mexican American who are more acculturated or who are second-
      and third-generation Mexican Americans.

PMID- 22150132
TI  - Driving themselves to drink: qualitative perspectives from "hardcore" DUI repeat
      offenders in Ohio.
AB  - Despite the continuing problem of repeat drunk driving (DUI) offenders, little is
      known of the characteristics of this population. This article reports findings
      from qualitative interviews with 12 incarcerated men who had been convicted for 5
      or more DUIs. Participants' sociodemographic characteristics, patterns of
      substance abuse, treatment history, attitudes toward positive behavioral change,
      and recommendations for improving treatment are described. Three groups were
      identified in regard to the degree of recognition of substance abuse and level of
      motivation to engage in treatment and post-release rehabilitation. Participants
      also offered suggestions to improve treatment strategies for repeat DUI offenders
      by tailoring diverse educational and counseling programs that target the
      differing types of DUI recidivists. The findings provide preliminary qualitative
      insight into a unique population that may be used to inform future studies.

PMID- 22150134
TI  - Transient host-parasitoid dynamics illuminate the practice of biological pest
      control.

PMID- 22150136
TI  - Are bone marrow mesenchymal stem cells-induced tenogenic progenitor cells
      identical to tendon progenitor cells?

PMID- 22150135
TI  - Caffeic Acid phenethyl ester protects blood-brain barrier integrity and reduces
      contusion volume in rodent models of traumatic brain injury.
AB  - A number of studies have established a deleterious role for inflammatory
      molecules and reactive oxygen species (ROS) in the pathology of traumatic brain
      injury (TBI). Caffeic acid phenethyl ester (CAPE) has been shown to exert both
      antioxidant and anti-inflammatory effects. The primary objective of the present
      study was to examine if CAPE could be used to reduce some of the pathological
      consequences of TBI using rodent models. Male Sprague-Dawley rats and C57BL/6
      mice were subjected to controlled cortical impact (CCI) injury. Blood-brain
      barrier (BBB) integrity was assessed by examining claudin-5 expression and the
      extravasation of Evans blue dye. The effect of post-injury CAPE administration on
      neurobehavioral function was assessed using vestibulomotor, motor, and two
      hippocampus-dependent learning and memory tasks. We report that post-TBI
      administration of CAPE reduces Evans blue extravasation both in rats and mice.
      This improvement was associated with preservation of the levels of the tight
      junction protein claudin-5. CAPE treatment did not improve performance in either
      vestibulomotor/motor function (tested using beam balance and foot-fault tests),
      or in learning and memory function (tested using the Morris water maze and
      associative fear memory tasks). However, animals treated with CAPE were found to
      have significantly less cortical tissue loss than vehicle-treated controls. These
      findings suggest that CAPE may provide benefit in the treatment of vascular
      compromise following central nervous system injury.

PMID- 22150137
TI  - Flaps pedicled on the superficial temporal artery and vein in facial
      reconstruction: a versatile option with a venous pitfall.
AB  - Flaps pedicled on the superficial temporal vessels are versatile in
      reconstruction of the face and scalp. Various tissues can be harvested and
      flexible pivot points and long pedicles allow for them to reach the entire face.
      Colour and texture match is good, and morbidity at the donor site is usually
      minimal. However, venous anatomy of the temporal area is unpredictable, and this
      anatomical point has not been clearly reported in papers and anatomical atlases.
      One must be aware of the risk of venous inconsistency and plan the pedicle
      accordingly. In the absence of a suitable vein, drainage can be provided through
      concomitant veins in a sufficient cuff of fascia around the pedicle's artery. We
      have reviewed published reports about reconstructive possibilities provided by
      temporal flaps, for descriptions of the venous drainage of the temporal area, and
      for salvage procedures in case of venous stasis. We present our own salvage
      procedure, the "modified poor man's leech", in which continuous venous oozing
      from a de-epithelialised area is maintained by topical heparin and low molecular
      weight heparin injections and may save a congested flap.

PMID- 22150138
TI  - Factors that affect variability in impairment of maxillary growth in patients
      with cleft lip and palate treated using the same surgical protocol.
AB  - No consensus exists about the causes of restriction of maxillary growth in
      patients with cleft lip and palate (CLP). The aim of this study was to try to
      identify causes of this impairment other than the influence of surgical technique
      and skill. We analysed a sample of 129 consecutively treated 5-year-old children
      with unilateral cleft lip and palate (UCLP), who were operated on by the same
      surgeon with the same protocol. Multiple cephalometric measurements of the sample
      showed a wide distribution of values for maxillary growth. We selected SNA as a
      value describing maxillary position. Variables investigated were: initial cast
      measurements; timing of lip and of gingivoalveoloplasty (GAP)/palatal surgery;
      and presence of permanent lateral incisors. The significance of differences was
      investigated with Pearson's correlation and analysis of variance (ANOVA). The
      factor most significantly linked with maxillary protrusion was the presence or
      absence of the permanent lateral incisor, even when peg laterals and
      supernumerary laterals were considered. Initial width of the palate measured on
      infant casts correlated with maxillary growth, but the timing of GAP did not.
      Although surgical skill and technique may be the most important factors
      responsible for impairment of maxillary growth, inherent tissue hypoplasia,
      possibly the lack of lateral incisors, seems to be the most important non
      iatrogenic factor.

PMID- 22150140
TI  - Suprathel((r)) causes less bleeding and scarring than Mepilex((r)) Transfer in
      the treatment of donor sites of split-thickness skin grafts.
AB  - Split-thickness skin grafts are routine in the treatment of deep dermal burns and
      various other wounds. Healing of the donor site of the graft has an impact on the
      total recovery of the patient. We conducted a prospective clinical study at
      Tampere University Hospital to compare the effect of two adhesive wound
      dressings, Suprathel((r)) and Mepilex((r)) Transfer. The donor sites of 22 split
      thickness skin grafts were studied, each of which was covered with Suprathel((r))
      and Mepilex((r)) Transfer dressings side by side. Significantly less pain and
      bleeding was associated with Suprathel((r)) treatment compared with Mepilex((r))
      Transfer (p < 0.05). Suprathel((r)) produced a better scar at the three months'
      follow-up as measured using the Vancouver Scar Scale (VSS). The results show that
      Suprathel((r)) is a better dressing for the donor sites than Mepilex((r))
      Transfer.

PMID- 22150139
TI  - Correction of myopathic blepharoptosis by check ligament suspension: clinical
      evaluation of 89 eyelids.
AB  - Myopathic blepharoptosis is a congenital anomaly of the eyelid. The levator
      muscle does not function because of primary myogenic atrophy. Different
      procedures based on eyelid suspension, or the simple or combined resection of the
      eyelid have been described. A simple dynamic suspension of the tarsus to the
      check ligament of the superior fornix, neither sacrificing nor adding any tissue
      was used for 89 procedures on 71 consecutive patients with primary myopathic
      blepharoptosis. Their mean age at operation was 16 years (range 2-58) and the
      follow up ranged from 2 months to 12 years. Ptosis was unilateral in 53 patients
      (33 left, 20 right) and bilateral in 18. Preoperatively 27 had mild ptosis (1-2
      mm), 33 moderate (3-4 mm), and 29 severe (>4 mm). The patients were divided into
      two groups: not previously operated on (50 patients/63 eyelids) and previously
      operated on by other techniques (21 patients/26 eyelids); both groups were
      compared for duration of procedure, normalisation rate, and number of revisions.
      In the unoperated group the normalisation rate was 81% (51 eyelids), and to
      achieve a good final result nine eyelids were revised once, while just three were
      reoperated on twice (19%). In the group previously operated on the normalisation
      rate was 69% (18 eyelids), while 3 eyelids needed one revision (12%). In
      unilateral cases the normalisation rate was 79% (42 eyelids) and in bilateral 75%
      (27 eyelids). In unilateral blepharoptosis there were 13% of revisions (7
      eyelids) while bilaterally there were 22% (8 eyelids). Despite a previous
      operation, the operating time of a unilateral correction was similar in both
      groups, while the number of revisions needed to achieve the final result was low
      for unilateral ptosis, but higher for bilateral ones. This simple atraumatic
      suspension technique produced an improvement in all cases and it seemed useful in
      both primary and secondary cases.

PMID- 22150141
TI  - Correction of pincer nail deformity with phenol.
AB  - From 2006 to 2009 we treated nine cases (11 toes) with pincer nail deformity of
      the first toe, using phenol. There were 8 women and 1 man, age range 9-81 years
      (mean 51). They were followed up for 7-17 months (mean 12) and all reported
      improvement of the pincer nail deformity and disappearance of pain from the first
      toes. Only one woman complained of a recurrent pincer nail deformity eight months
      after the first treatment, and the procedure was repeated. The mechanism of
      improvement is contraction of the phenolised wound away from the lateral nail
      fold, which gradually stretches and flattens the nail bed. We conclude that this
      technique is a simple and effective treatment for pincer nail deformity.

PMID- 22150142
TI  - Rare giant secondary cutis verticis gyrata.
AB  - We report a case of cerebriform intradermal naevus (CIN) of the scalp in a 17
      year-old girl. The clinical and histopathological presentations of the case are
      described and the diagnostic and therapeutic aspects presented.

PMID- 22150143
TI  - Post-traumatic false aneurysm in a digital artery of the finger.
AB  - Despite the high incidence of trauma involving the hand and digits, traumatic
      aneurysms in this region are rarely seen and few are reported. We describe a
      false aneurysm of a digital artery caused by a dog bite.

PMID- 22150144
TI  - Features of wound healing shown by fibroblasts obtained from the superficial and
      deep dermis.
AB  - Dermal fibroblasts (DF) obtained from the superficial dermal layer and those from
      the deep dermal layer have different cellular functions. These differences are
      often associated with excessive scarring; they also influence early wound
      healing. We therefore investigated the differences between superficial and deep
      dermal fibroblasts with special emphasis on their contractile properties, and
      ability to produce connective tissue. We investigated their proliferation
      kinetics, ability to contract collagen lattices, and chronological mRNA
      expression of eight genes associated with wound healing. To estimate the changes
      in the differences between them during the early phase of wound healing, we
      investigated mRNA expression in bFGF supplemented medium because bFGF is a
      representative cytokine that is familiar to clinicians. Superficial DF
      proliferate faster than deep DF in culture, whereas deep DF are better at
      contracting collagen lattices than superficial ones. In realtime analysis of
      polymerase chain reaction, the expression of type I and III collagen,
      fibronectin, TGF beta1 and beta3, and connective tissue growth factor were higher
      in deep DF than in superficial DF, while the expression of TGF beta2 was higher
      in superficial DF. After bFGF supplementation, the relative dominance of mRNA
      expression between superficial and deep DF remained constant except for the
      expression of collagenase. According to our analysis, deep DF are superior to
      superficial DF at promoting wound healing (particularly contraction and
      production of connective tissue). The intradermal distribution of DF is
      appropriate for efficient wound healing.

PMID- 22150145
TI  - Laparoscopic rectosigmoid flap vaginoplasty.
AB  - Various methods have been developed for vaginoplasty, of which the rectosigmoid
      flap has its own advantages including sufficient increase in the vaginal length
      and lower incidence of complications such as contracture or strain after
      vaginoplasty. Laparoscopic operation can greatly minimise the abdominal scar
      associated with laparotomy and allow cosmetically superior outcomes. Its
      minimally invasive procedure can also achieve rapid recovery and shorten the
      duration of hospital stay. Twelve patients (age range 18-40 years) had
      vaginoplasty using the rectosigmoid colon. We evaluated the ecological changes of
      the neovagina from the change of pH in the neovagina, culture of the normal
      flora, and vaginal wall biopsy taken 6 to 12 months postoperatively. Details of
      sexual activity were also examined. No patient from interviews developed vaginal
      narrowing as a result of the contracture that caused painful intercourse, or had
      smelly discharge or spontaneous bleeding from the vagina. Laparoscopic procedures
      may need only five-openings of 1-1.5 cm in diameter. Mean operating time was 130
      minutes (IQR, 113-140) and duration of hospital stay 8.5 days (IQR, 7-11). Twelve
      months postoperatively the intravaginal pH was about 6. In one case, the
      histological test showed that the original columnar cell of the intestinal mucosa
      had been transformed to stratified squamous cell tissue. The key to the
      vaginoplasty is that it should give functional satisfaction and a minimal rate of
      complications. The laparoscopic rectosigmoid flap technique of vaginoplasty
      allowed less morbidity and excellent aesthetic and functional postoperative
      outcomes.

PMID- 22150146
TI  - Randomised study of non-bridging external fixation compared with intramedullary
      fixation of unstable distal radial fractures.
AB  - This is a randomised study to compare two types of osteosynthesis to mobilise
      wrists after distal fractures of the radius. Inclusion criteria were Older type 2
      and 3 fractures. External fixation was managed with Hoffmann II compact non
      bridging. Internal fixation was managed with Micronail. Patients were followed up
      for 12 weeks. The primary outcome was the results of the disabilities of arm,
      shoulder and hand (DASH) questionnaire. The secondary outcomes were answers to
      the patient-rated wrist evaluation (PRWE), grip strength, satisfaction, radial
      length, and volar tilt. Thirty patients were randomised to have external fixation
      and 31 to have internal fixation.There were no significant differences in DASH
      score. Internal fixation gave significantly better grip strength at five (p =
      0.00) and 12 weeks (p = 0.03). The operating time was significantly shorter (p =
      0.00) when non-bridging external fixation was used, and there were minor
      radiological differences. An activity-based costing analysis showed that external
      fixation cost three times more overall.

PMID- 22150147
TI  - New method of assessing pinch function in children with anomalies of the hands.
AB  - We designed a method for the evaluation of pinch function in children that uses a
      tape measure, which is suitable in size and weight for the infant's hand. Our aim
      was to investigate the value of the tape measure in the evaluation of pinch
      function in children. Thirty-two hands of 27 children with congenital anomalies
      that we operated on in our hospital were included. The assessment of pinch
      function was made using a tape measure. The criteria were evaluated as follows:
      grasp = 1; push button = 2; pinch the end of the measuring tape = 3; pull out
      tape by side pinch = 4; and pull out tape by pulp pinch = 5. We assessed the
      relation between the scoring by tape measure and parents' preoperative
      assessment. We also examined the relations between the increase in score
      evaluated by the tape measure method and parents' assessment of postoperative
      improvement in pinch function. The mean preoperative score by the tape measure
      assessment of pinch function in the unimpaired group according to the parents'
      evaluation was significantly higher than that in the impaired group. Preoperative
      evaluation using the tape measure method correlated with the parents' evaluation.
      The increase in score in the "remarkably improved" group was significantly higher
      than that of those in the "no change" and "improved" groups. The tape measure
      method reflected the parents' evaluation, and could be a useful test for the
      evaluation of pinch function in children.

PMID- 22150148
TI  - Use of tissue expansion to allow reconstruction of the back after wide resection
      of a diffuse neurofibroma.
AB  - Diffuse neurofibroma presents as a diffuse overgrowth of subcutaneous tissue, and
      usually involves the face, scalp, neck, or chest, but rarely occurs in the back.
      The management of large soft tissue defects after wide resection of a diffuse
      neurofibroma is a major surgical challenge. We report the case of a diffuse
      neurofibroma of the back that required reconstruction after wide resection of the
      tumour using an expanded myocutaneous advancement flap and a tissue expander.
      Tissue expansion is essentially a simple technique for expanding available normal
      skin, and it provides optimally matched skin in terms of colour, texture, hair
      bearing qualities, and sensation.

PMID- 22150149
TI  - Partial laceration of the flexor tendon as an unusual cause of trigger finger.
AB  - We present two cases of trigger finger caused by partial laceration of a flexor
      tendon. Both patients had preceding skin injury and required operative treatment
      with resection of the lacerated portion of the tendon and incision of the A1
      pulley. We describe keys to the diagnosis of this type of lesion.

PMID- 22150150
TI  - Importance of the reconstruction of the extensor retinaculum after injury.
AB  - We reconstructed an extensive soft tissue defect of the dorsum of the left wrist
      after an injury using a free anterolateral thigh flap and a tendon graft, and
      intending to substitute the extensor retinaculum for the fascia in this flap. As
      a result, maximum function of the extension mechanism was restored to the
      reconstructed hand.

PMID- 22150151
TI  - Molecular diversity of methanogens and identification of Methanolobus sp. as
      active methylotrophic Archaea in Lonar crater lake sediments.
AB  - Soda lakes constitute extreme aquatic ecosystems with remarkably high primary
      productivity rates, but information on the diversity and activity of methanogens
      in such environments is sparse. Using 16S rRNA and functional genes, we
      investigated the diversity of methanogens in the sediments of Lonar Lake, a
      unique saline and alkaline ecosystem formed by meteorite impact in the Deccan
      basalts. Although domain and phylum level 16S rRNA gene libraries were dominated
      by phylotypes related to Halobacteriales, sequences related to potentially novel
      Archaea within the orders Methanosarcinales and Methanomicrobiales were obtained
      together with a significant fraction of sequences representing uncultivated
      Euryarchaeota [Correction added after online publication 16 April 2012: orders
      'Methanosarcina and Methanomicrobiaceae' changed to 'Methanosarcinales and
      Methanomicrobiales']. To identify the active methylotrophic Archaea involved in
      methanogenesis, mRNA transcripts of mcrA were retrieved from methanol consuming
      and methane emitting sediment microcosms at two different time points. Reverse
      transcription PCR, qPCR, DGGE fingerprint, and clone library analysis showed that
      the active Archaea were closely related to Methanolobus oregonensis. To our
      knowledge, this is the first study identifying active methylotrophic methanogens
      in such an environment.

PMID- 22150152
TI  - Reproducibility of facial soft tissue thicknesses for craniofacial reconstruction
      using cone-beam CT images.
AB  - The purpose of this study was to evaluate the reproducibility of the soft tissue
      (ST) thicknesses at 31 landmarks using the cone-beam computed tomography (CBCT)
      images obtained from 20 adult subjects. Four observers carried out ST thickness
      measurements using Skull Measure software, and the inter- and intra-observer
      error rates were evaluated. Only five of 31 landmarks showed significant
      differences in recorded ST thickness between the observers. When excluding
      inexperienced observers, only one landmark showed a significant difference
      between the observers. Regarding the intra-observer reproducibility, the ST
      thickness measurements at three landmarks showed low correlation coefficients.
      The results of this study indicate that CBCT images can be used to measure ST
      thickness with high reproducibility. However, some landmarks need to be redefined
      to reliably measure ST thickness on CBCT images.

PMID- 22150153
TI  - Analyzing the function of a hox gene: an evolutionary approach.
AB  - We present an evolutionary approach to dissecting conserved developmental
      mechanisms. We reason that important mechanisms for making the bodyplan will act
      early, to generate the major features of the body and that they will be conserved
      in evolution across many metazoa, and thus, that they will be available in very
      different animals. This led to our specific approach of microarrays to screen for
      very early conserved developmental regulators in parallel in an insect,
      Drosophila and a vertebrate, Xenopus. We screened for the earliest conserved
      targets of the ectopically expressed hox gene Hoxc6/Antennapedia in both species
      and followed these targets up, using in situ hybridization, in the Xenopus
      system. The results indicate that relatively few of the early Hox target genes
      are conserved: these are mainly involved in the specification of the antero
      posterior body axis and in gastrulation.

PMID- 22150154
TI  - Adherence to the U.S. Preventive Services Task Force 2002 osteoporosis screening
      guidelines in academic primary care settings.
AB  - BACKGROUND: Osteoporosis is very common in older women in the United States.
      Osteoporotic fractures cause significant morbidity and mortality, as well as high
      healthcare costs. Since 2002, the United States Preventive Services Task Force
      (USPSTF) has recommended screening for osteoporosis of all women aged >=65. Our
      objective was to determine adherence to osteoporosis screening guidelines by
      primary care internists in a large academic medical center and to assess if
      adherence varies based on provider gender or practice location. METHODS: This was
      a retrospective electronic medical record (EMR) review. All women aged >=65 who
      were seen in the General Internal Medicine Center (GIMC) or the Women's Health
      Care Center (WHCC) at the University of Washington Medical Center by internal
      medicine attending physicians between January 1, 2006, and February 2, 2008, were
      included in the study. We determined if the patient had a dual energy x-ray
      absorptiometry (DEXA) study in the EMR database. We calculated the percentage of
      patients screened per provider and also compared the rate of screening for male
      vs. female providers and for GIMC vs. WHCC providers. RESULTS: Of the 1363 women
      included in the study, 70% had documentation of a DEXA study. Adherence to
      screening recommendations for individual providers varied from 33% to 100%.
      Screening was more likely to occur in the WHCC than in the GIMC (79.2% vs. 66.7%,
      p<0.001). Although women providers were more likely to screen than their male
      counterparts (72.2% vs. 66.1%, p=0.023), this relationship did not hold true
      after excluding women providers from the WHCC. CONCLUSIONS: We found good
      adherence to the USPSTF 2002 guidelines for osteoporosis screening in women aged
      >=65 years by primary care physicians in a large urban academic medical center.
      The practice site and not gender of the provider resulted in significantly
      different screening rates.

PMID- 22150155
TI  - Ultrastructure of the spermatozoon of Bothriocotyle sp. (Cestoda:
      Bothriocephalidea), a parasite of Schedophilus velaini (Sauvage, 1879)
      (Perciformes: Centrolophidae) in Senegal.
AB  - The mature spermatozoon of Bothriocotyle sp. is filiform and tapered at both
      extremities. It possesses 2 axonemes of unequal length, showing the 9 + "1"
      pattern of Trepaxonemata. The anterior extremity exhibits a crest-like body.
      Thereafter, the crest-like body disappears, and the first axoneme is surrounded
      by a ring of cortical microtubules (about 27 units) that persist until the
      appearance of the second axoneme. This ring of cortical microtubules is
      characteristic only for species of Bothriocephalidea and represents a very useful
      phylogenetic character. The spermatozoon cytoplasm is slightly electron-dense and
      contains numerous electron-dense granules of glycogen in several regions. The
      anterior and posterior extremities of the spermatozoon lack cortical
      microtubules. The posterior extremity of the spermatozoon of Bothriocotyle sp.
      possesses a nucleus and a disorganized axoneme, which also characterizes
      spermatozoa of the Echinophallidae studied to date.

PMID- 22150156
TI  - Risk of hypoglycemia in older veterans with dementia and cognitive impairment:
      implications for practice and policy.
AB  - OBJECTIVES: To examine the relationship between management of diabetes mellitus
      and hypoglycemia in older adults with and without dementia and cognitive
      impairment. DESIGN: Cross-sectional database analysis of veterans aged 65 years
      and older stratified according to dementia, cognitive impairment, age,
      antiglycemic medications, and glycosylated hemoglobin (Hba1c) level. SETTING:
      Research database with linked clinical, laboratory, pharmacy, and International
      Classification of Diseases, Ninth Revision, Clinical Modification, codes.
      PARTICIPANTS: Four hundred ninety-seven thousand nine hundred veterans aged 65
      and older with diabetes mellitus who obtained services from the Department of
      Veterans Affairs in fiscal years (FYs) 2002 and 2003. MEASUREMENTS: Hypoglycemia,
      the outcome variable, was identified from outpatient visits, emergency department
      and inpatient admission codes in FY2003. Independent variables (FY2002-03)
      included dementia and cognitive impairment, comorbid conditions, extended care
      and nursing home stays, demographics, antiglycemic medication, and HbA1c levels.
      RESULTS: Prevalence of combined dementia and cognitive impairment was 13.1% for
      individuals aged 65 to 74 and 24.2% for those aged 75 and older. Mean HbA1c
      levels were 7.0 +/- 1.3% for all participants and 6.9 +/- 1.3% for those with
      dementia. The proportion of participants taking insulin was higher in those with
      dementia or cognitive impairment (30%) than in those with neither condition
      (24%). Of all participants taking insulin, more with dementia (26.5%) and
      cognitive impairment (19.5%) were hypoglycemic than of those with neither
      condition (14.4%). For all participants, unadjusted odds ratios (ORs) for
      hypoglycemia were 2.42 (95% confidence interval (CI) = 2.36-2.48) for dementia
      and 1.72 (95% CI = 1.65-1.79) for cognitive impairment; adjusted ORs were 1.58
      (95% CI = 1.53-1.62) for dementia and 1.13 (95% CI = 1.08-1.18) for cognitive
      impairment. CONCLUSION: Diabetes mellitus was managed more intensively in older
      veterans with dementia and cognitive impairment, and dementia and cognitive
      impairment were independently associated with greater risk of hypoglycemia.

PMID- 22150157
TI  - Melamine causes apoptosis of rat kidney epithelial cell line (NRK-52e cells) via
      excessive intracellular ROS (reactive oxygen species) and the activation of p38
      MAPK pathway.
AB  - There was an outbreak of urinary stones associated with consumption of melamine
      tainted milk products in 2008 in China, leading to serious illness of many
      infants and even death. We have recently demonstrated that melamine causes
      oxidative damage on the NRK (normal rat kidney)-52e cells. The objective of this
      study was to explore the cellular signalling pathway that mediates the cell
      apoptosis induced by melamine in the NRK-52e cells. Fluorescence microscope
      showed that melamine enhanced intracellular ROS (reactive oxygen species) levels
      of the NRK-52e cells. AO/EB (acridine orange/ethidium bromide) staining and flow
      cytometry revealed that melamine increased apoptotic and necrotic percentages of
      the NRK-52e cells in a dose-dependent manner. Notably, MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assays and flow
      cytometry displayed that SB203580, an inhibitor for p38 MAPK (mitogen-activated
      protein kinase) pathway, increased the proliferation of the NRK-52e cells and
      reduced the apoptotic and necrotic percentages of the NRK-52e cells. Western
      blots further demonstrated that p38 phosphorylation was activated by melamine in
      the NRK-52e cells and inhibitor SB203580 blocked the increase of p38
      phosphorylation induced by melamine. Together, these results suggested that
      melamine causes apoptosis of the NRK-52e cells via excessive intracellular ROS
      and the activation of p38 MAPK pathway. This study thus offers a novel insight
      into molecular mechanisms by which melamine has adverse cytotoxicity on renal
      tubular epithelial cells.

PMID- 22150158
TI  - The endo-1,4-beta-glucanase Korrigan exhibits functional conservation between
      gymnosperms and angiosperms and is required for proper cell wall formation in
      gymnosperms.
AB  - The evolution of compositional polymers and their complex arrangement and
      deposition in the cell walls of terrestrial plants included the acquisition of
      key protein functions. A membrane-bound endoglucanase, termed Korrigan (KOR), has
      been shown to be required for proper cellulose synthesis. To date, no extensive
      characterization of the gymnosperm KOR has been undertaken. Characterization of
      the white spruce (Picea glauca) gene encoding KOR (PgKOR) shows conserved protein
      features such as polarized targeting signals and residues predicted to be
      essential for catalytic activity. The rescue of the Arabidopsis thaliana kor1-1
      mutant by the expression of PgKOR suggests gene conservation, providing evidence
      for functional equivalence. Analyses of endogenous KOR expression in white spruce
      revealed the highest expression in young developing tissues, which corresponds
      with primary cell wall development. Additionally, RNA interference of the
      endogenous gymnosperm gene substantially reduced growth and structural glucose
      content, but had no effect on cellulose ultrastructure. Partial functional
      conservation of KOR in gymnosperms suggests that its role in cell wall synthesis
      dates back to 300 million yr ago (Mya), predating angiosperms, which arose 130
      Mya, and shows that proteins contributing to proper cellulose deposition are
      important conserved features of vascular plants.

PMID- 22150159
TI  - Health inequalities: a response to Scambler.

PMID- 22150160
TI  - A Golgi-localized MATE transporter mediates iron homoeostasis under osmotic
      stress in Arabidopsis.
AB  - Iron is an essential micronutrient that acts as a cofactor in a wide variety of
      pivotal metabolic processes, such as the electron transport chain of respiration,
      photosynthesis and redox reactions, in plants. However, its overload exceeding
      the cellular capacity of iron binding and storage is potentially toxic to plant
      cells by causing oxidative stress and cell death. Consequently, plants have
      developed versatile mechanisms to maintain iron homoeostasis. Organismal iron
      content is tightly regulated at the steps of uptake, translocation and
      compartmentalization. Whereas iron uptake is fairly well understood at the
      cellular and organismal levels, intracellular and intercellular transport is only
      poorly understood. In the present study, we show that a MATE (multidrug and toxic
      compound extrusion) transporter, designated BCD1 (BUSH-AND-CHLOROTIC-DWARF 1),
      contributes to iron homoeostasis during stress responses and senescence in
      Arabidopsis. The BCD1 gene is induced by excessive iron, but repressed by iron
      deficiency. It is also induced by cellular and tissue damage occurring under
      osmotic stress. The activation-tagged mutant bcd1-1D exhibits leaf chlorosis, a
      typical symptom of iron deficiency. The chlorotic lesion of the mutant was
      partially recovered by iron feeding. Whereas the bcd1-1D mutant accumulated a
      lower amount of iron, the iron level was elevated in the knockout mutant bcd1-1.
      The BCD1 protein is localized to the Golgi complex. We propose that the BCD1
      transporter plays a role in sustaining iron homoeostasis by reallocating excess
      iron released from stress-induced cellular damage.

PMID- 22150161
TI  - Liquid chromatography-tandem mass spectrometry analysis of human adrenal vein
      corticosteroids before and after adrenocorticotropic hormone stimulation.
AB  - CONTEXT: Although steroid hormones produced by the adrenal gland play critical
      roles in human physiology, a detailed quantitative analysis of the steroid
      products has not been reported. The current study uses a single methodology
      (liquid chromatography-tandem mass spectrometry, LC-MS/MS) to quantify ten
      corticosteroids in adrenal vein (AV) samples pre- and post-adrenocorticotropic
      hormone (ACTH) stimulation. DESIGN/METHODS: Three men and six women with a
      diagnosis of an adrenal aldosterone-producing adenoma (APA) were included in the
      study. Serum was collected from the iliac vein (IV) and the AV contralateral to
      the diseased adrenal. Samples were collected, before and after administration of
      ACTH. LC-MS/MS was then used to quantify serum concentrations of unconjugated
      corticosteroids and their precursors. RESULTS: Prior to ACTH stimulation, the
      four most abundant steroids in AV were cortisol (90%), cortisone (4%),
      corticosterone (3%) and 11-deoxycortisol (0.8%). Post-ACTH administration,
      cortisol remained the major adrenal product (79%); however, corticosterone became
      the second most abundantly produced adrenal steroid (11%) followed by
      pregnenolone (2.5%) and 17alpha-hydroxypregnenolone (2%). ACTH significantly
      increased the absolute adrenal output of all ten corticosteroids measured (P <
      0.05). The four largest post-ACTH increases were pregnenolone (300-fold),
      progesterone (199-fold), 17alpha-hydroxypregnenolone (187-fold) and
      deoxycorticosterone (82-fold). CONCLUSION: Using LC-MS/MS, we successfully
      measured 10 corticosteroids in peripheral and AV serum samples under pre- and
      post-ACTH stimulation. This study demonstrates the primary adrenal steroid
      products and their response to ACTH.

PMID- 22150162
TI  - Cancer risk among patients with systemic sclerosis: a nationwide population study
      in Taiwan.
AB  - OBJECTIVES: Systemic sclerosis (SSc) has been associated with high cancer risk.
      We compared the cancer risk among SSc patients with that among the general
      Taiwanese population. METHODS: The catastrophic illness registry of the Taiwan
      National Health Insurance Research Dataset (NHIRD) was used to identify patients
      diagnosed with SSc and cancer in Taiwan during 1996-2008. The standardized
      incidence ratio (SIR) for cancer was calculated, and mortality was ascertained
      using the data from the National Death Registry. RESULTS: Data analysis revealed
      that 2053 (472 men, 1581 women) Taiwanese individuals were diagnosed with SSc
      during the study period and 83 (30 men, 53 women) had cancer. The incidence of
      cancer was 6.9/1000 person-years. The most common cancer sites in male SSc
      patients were the lung (n = 10), oral cavity and pharynx (n = 8), and
      gastrointestinal tract (n = 4), and those in female patients were the breast (n =
      11), lungs (n = 11), and blood (n = 6). Compared to the Taiwanese population of
      1996, the all-cancer SIR for SSc was 1.63 [95% confidence interval (CI) 1.31
      2.01]. Cancer risk was elevated for cancers of the lung (SIR 4.20), oral cavity
      and pharynx (SIR 3.67), and blood (SIR 3.50). A cancer diagnosis in SSc patients
      was associated with a hazard ratio (HR) of 2.15 (95% CI 1.30-3.53). Among cancer
      patients, a diagnosis of SSc was not associated with increased mortality.
      CONCLUSIONS: SSc patients are at high risk of developing cancer, especially of
      the lung, oral cavity and pharynx, and blood.

PMID- 22150163
TI  - Adversarial risk analysis for counterterrorism modeling.
AB  - Recent large-scale terrorist attacks have raised interest in models for resource
      allocation against terrorist threats. The unifying theme in this area is the need
      to develop methods for the analysis of allocation decisions when risks stem from
      the intentional actions of intelligent adversaries. Most approaches to these
      problems have a game-theoretic flavor although there are also several interesting
      decision-analytic-based proposals. One of them is the recently introduced
      framework for adversarial risk analysis, which deals with decision-making
      problems that involve intelligent opponents and uncertain outcomes. We explore
      how adversarial risk analysis addresses some standard counterterrorism models:
      simultaneous defend-attack models, sequential defend-attack-defend models, and
      sequential defend-attack models with private information. For each model, we
      first assess critically what would be a typical game-theoretic approach and then
      provide the corresponding solution proposed by the adversarial risk analysis
      framework, emphasizing how to coherently assess a predictive probability model of
      the adversary's actions, in a context in which we aim at supporting decisions of
      a defender versus an attacker. This illustrates the application of adversarial
      risk analysis to basic counterterrorism models that may be used as basic building
      blocks for more complex risk analysis of counterterrorism problems.

PMID- 22150164
TI  - Using a multi-faceted approach to determine the changes in bacterial cell surface
      properties influenced by a biofilm lifestyle.
AB  - Biofilm formation is a developmental process in which initial reversible adhesion
      is governed by physico-chemical forces, whilst irreversible adhesion is mediated
      by biological changes within a cell, such as the production of extracellular
      polymeric substances. Using two bacteria, E. coli MG1655 and B. cereus ATCC
      10987, this study establishes that the surface of the bacterial cell also
      undergoes specific modifications, which result in biofilm formation and
      maintenance. Using various surface characterisation techniques and proteomics, an
      increase in the surface exposed proteins on E. coli cells during biofilm
      formation was demonstrated, along with an increase in hydrophobicity and a
      decrease in surface charge. For B. cereus, an increase in the surface
      polysaccharides during biofilm formation was found as well as a decrease in
      hydrophobicity and surface charge. This work therefore shows that surface
      modifications during biofilm formation occur and understanding these specific
      changes may lead to the formulation of effective biofilm control strategies in
      the future.

PMID- 22150165
TI  - Intracranial germ cell tumours. A review with special reference to endocrine
      manifestations.
AB  - EPIDEMIOLOGY: Intracranial germ cell tumours (icGCTs) represent 3-15% of primary
      paediatric intracranial neoplasms with a considerable geographical variation in
      incidence. Ninety percent of patients diagnosed with icGCTs are under 20 years of
      age. PATHOLOGY: Histologic characteristics and investigation of the tumour
      markers beta-human chorionic gonadotropin (beta-hCG) and alpha-fetoprotein (AFP)
      help define the different categories of icGCTs. The tumours are divided into two
      major groups called germinomas and non-germinomatous GCTs (NGGCTs). CLINICAL
      PRESENTATION: The clinical symptoms depend on the size and location of tumour in
      the brain, which is most commonly in the pineal or suprasellar region. Pineal
      GCTs often present with neurological symptoms because of their tendency to cause
      increased intracranial pressure. Suprasellar GCTs are often accompanied by
      endocrine abnormalities such as diabetes insipidus (DI), growth retardation and
      precocious or delayed puberty. DIAGNOSIS: A combination of clinical findings,
      endocrine and tumour marker evaluation, spinal fluid cytology, magnetic resonance
      imaging (MRI) and biopsy helps verifying the diagnosis of an icGCT. A summary of
      published data (n = 97) revealed that >90% of patients at diagnosis had at least
      one endocrine abnormality, DI being the most common (>80%). TREATMENT:
      Classification of tumour is important for choice of treatment and for prognosis.
      A combination of chemotherapy and radiotherapy is often used, since most icGCTs
      have a great sensitivity to these treatment modalities. CONCLUSION: Endocrine
      symptoms are very frequently appearing in patients with icGCTs and they can
      present long before neuroimaging verification of tumour is possible. It is of the
      outmost importance to have the diagnosis of icGCTs in mind when children,
      adolescents and young adults are presenting with endocrine irregularities,
      because most icGCTs are very sensitive to radiotherapy and chemotherapy, and
      early onset of treatment is important in order to minimize morbidity and
      mortality.

PMID- 22150166
TI  - The risk of cancer among persons with a history of injecting drug use in Sweden -
      a cohort study based on participants in a needle exchange program.
AB  - BACKGROUND: Injecting drug use (IDU) may lead to exposure to a range of
      carcinogenic agents. We investigated the risk and distribution of cancers among
      individuals with a history of IDU in Sweden. MATERIAL AND METHODS: The cancer
      incidence in a cohort of longitudinally followed participants in a needle
      exchange program (NEP), recruited between 1987 and 2007, was compared to that in
      the Swedish general population, matching for age group and gender. Baseline
      demographic and drug use data were collected and longitudinal testing of
      serological markers for HIV, hepatitis B and C virus was performed during NEP
      participation. Standardized incidence ratios (SIR) for types of cancer found in
      the study cohort were calculated, using data from the Swedish National Cancer
      Registry for reference. RESULTS: The mean follow-up time for the 3255
      participants was 11.8 years, constituting 38 419 person years at risk. The mean
      age at end of follow-up was 42.7 years, and 75% of participants were men. Seventy
      eight cases of cancer were observed (SIR 1.1 [95% CI = 0.9-1.4]). The SIR was
      significantly increased for five cancer types among men; primary liver,
      laryngeal, lung, oropharyngeal and non-melanoma skin cancer (respective SIR 12.8
      [95% CI = 4.2-30.0], 9.2 [95% CI = 1.9-26.8], 3.2 [95% CI = 1.5-6.1], 7.3 [95% CI
      = 1.5-21.2], and 3.5 [95% CI = 1.1-8.2]), and for cancers of endocrine organs
      among women (5.3 [95% CI = 1.7-12.4]). CONCLUSION: Although the standardized
      overall cancer incidence in this relatively young IDU cohort was similar to that
      in the general population, the risk of specific types of cancer was significantly
      increased, suggesting that IDU confers elevated risks for certain malignancies.
      These findings prompt further studies to investigate causative factors and
      suggest the need for surveillance among persons with a history of IDU.

PMID- 22150167
TI  - Validation of oesophageal cancer surgery data in the Swedish Patient Registry.
AB  - BACKGROUND: The Swedish Patient Registry provides data about diagnoses and
      surgical procedures for research purposes. There are, however, almost no
      validation studies of the data on surgical procedures, and none of oesophageal
      cancer surgery. MATERIAL AND METHODS: This was a validation study of the accuracy
      of codes representing oesophageal cancer resection, surgical approach and
      oesophageal substitute in the Swedish Patient Registry during the period 1987
      2005. The registered data were compared with a thorough review of the
      corresponding operation charts collected from medical records. RESULTS: Among
      1358 patients with a code representing oesophageal resection in the Patient
      Registry, the positive predictive value was 99.6%. The dominant surgical
      procedures in terms of surgical approach (transthoracic) and type of oesophageal
      substitute (gastric conduit) had positive predictive values of 99.8% and 99.4%,
      respectively. The more rare procedures with regards to approach (transhiatal) and
      substitute (bowel) had lower positive predictive values of 68.8% and 68.5%,
      respectively. CONCLUSION: The high accuracy of the data regarding oesophageal
      cancer resection in the Swedish Patient Registry stresses its appropriateness for
      research purposes.

PMID- 22150168
TI  - A phase II trial of gefitinib in patients with rising PSA following radical
      prostatectomy or radiotherapy.

PMID- 22150169
TI  - Discussions of cancer clinical trials with the National Cancer Institute's Cancer
      Information Service.
AB  - Clinical trials are essential for the development of new and effective treatments
      for cancer; however, participation rates are low. One reason for this is lack of
      knowledge about clinical trials. This study assessed how often clinical trials
      are discussed on calls to National Cancer Institute's Cancer Information Service
      (CIS). The authors quantitatively analyzed 283,094 calls to the CIS (1-800-4
      CANCER) over 3 years (2006-2008). They calculated descriptive statistics and
      multivariate regressions to determine whether specific caller characteristics are
      associated with the presence of a clinical trials discussion. In addition, 2
      focus groups were conducted with CIS information specialists (n=12) to provide
      insight into the findings. The authors found that approximately 9.3% of CIS calls
      discussed clinical trials, with higher percentages for patients (12.5%) and
      family members (15.4%). Calls with Hispanics, Blacks, and Spanish speakers were
      less likely to include a conversation. For all cancers, patients who are in
      treatment or experiencing a recurrence were statistically significantly more
      likely to discuss clinical trials. CIS information specialists reported callers'
      limited knowledge of clinical trials. The CIS has the unique ability to make a
      substantial effect in educating patients about clinical trials as an option in
      cancer treatment and care.

PMID- 22150171
TI  - Global functioning and suicide among Chinese rural population aged 15-34 years: a
      psychological autopsy case-control study.
AB  - As the relationship between global functioning and young suicide remains unclear
      in rural China, this study was aimed to explore the relationship between them.
      Data of 391 rural suicides and 416 controls, all aged 15-34 years in three
      provinces in China were used for this study. The Global Assessment of Functioning
      (GAF) scale was adopted to assess global functioning of suicides and controls.
      The results showed that GAF score was stronger than mental illness in predicting
      suicide in China. Different correlates of GAF score were found between suicides
      and controls. Unsurprisingly, GAF score was significantly correlated with mental
      illness in both suicides and controls. Different characteristics were also found
      among three types of suicide which were classified using GAF score. Assessing
      global functioning is useful and GAF scale should be regularly used in suicide
      prevention practice.

PMID- 22150172
TI  - Another issue of the Journal of Social Work in End-of-Life & Palliative Care.

PMID- 22150170
TI  - Effect of high velocity, large amplitude stimuli on the spread of depolarization
      in S1 "barrel" cortex.
AB  - We examined the effect of large, controlled whisker movements, delivered at a
      high speed, on the amplitude and spread of depolarization in the anesthetized
      mouse barrel cortex. The stimulus speed was varied between 1500 and 6000 degrees
      /s and the extent of movement was varied between 4 degrees  and 16 degrees . The
      rate of rise of the response was linearly related to the rate of rise of the
      stimulus. The initial spatial extent of cortical activation was also related to
      the rate of rise of the stimulus: that is, the faster the stimulus onset, the
      faster the rate of rise of the response, the larger the extent of cortex
      activated initially. The spatial extent of the response and the rate of rise of
      the response were not correlated with changes in the deflection amplitude.
      However, slower, longer lasting stimuli produced an Off response, making the
      actual extent of activation larger for the slowest rising stimuli. These results
      indicate that the spread of cortical activation depends on stimulus features.

PMID- 22150173
TI  - The growth of research in end-of-life care in nursing homes.

PMID- 22150174
TI  - Reflections on brain death and "process".

PMID- 22150175
TI  - Developing the science of end-of-life and palliative care research: National
      Institute of Nursing Research summit.
AB  - A rare opportunity to examine accomplishments and identify ways to advance
      research in end-of-life and palliative care was offered by the National Institute
      of Nursing Research (NINR) through a summit meeting held in August 2011. The
      Science of Compassion: Future Directions in End-of-Life and Palliative Care
      brought together nationally recognized leaders in end-of-life and palliative care
      research, including grantees of NINR, as well as more than 700 attendees from all
      disciplines. It was an exciting affirmation of the importance of moving forward
      in the field. Presented in this article is a summary of the summit and a call to
      action for end-of-life and palliative care social workers to engage in seeking
      funding to conduct needed research and to ensure our unique perspective is
      represented.

PMID- 22150176
TI  - Health care costs in end-of-life and palliative care: the quest for ethical
      reform.
AB  - Health reform in the United States must address both access to medical services
      and universal insurance coverage, as well as health care cost containment.
      Uncontrolled health care costs will undermine improvements in access and coverage
      in the long-run, and will also be detrimental to other important social programs
      and goals. Accordingly, the authors offer an ethical perspective on health care
      cost control in the context of end-of-life and palliative care, an area
      considered by many to be a principal candidate for cost containment. However, the
      policy and ethical challenges may be more difficult in end-of-life care than in
      other areas of medicine. Here we discuss barriers to developing high quality,
      cost effective, and beneficial end-of-life care, and barriers to maintaining a
      system of decision making that respects the wishes and values of dying patients,
      their families, and caregivers. The authors also consider improvements in present
      policy and practice-such as increased timely access and referral to hospice and
      palliative care; improved organizational incentives and cultural attitudes to
      reduce the use of ineffective treatments; and improved communication among health
      professionals, patients, and families in the end-of-life care planning and
      decision-making process.

PMID- 22150177
TI  - Stress and grief among family caregivers of older adults with cancer: a
      multicultural comparison from Hawai'i.
AB  - In this study the authors investigated stress, anticipatory mourning, and
      cultural practices among family caregivers from independent and interdependent
      cultural groups. Focus groups were used to collect data from 56 caregivers
      providing care to family members with terminal cancer, representing four cultural
      groups in Hawai'i: Chinese, European Americans, Japanese, and Native Hawaiians.
      Participants from all four cultural groups identified similar stressors and
      agreed that support groups helped them cope with the stresses and sadness they
      were experiencing and differed in culturally based motivations for caregiving,
      perceived roles, and processing of grief. The findings of this study indicated a
      need for additional conceptual models of the caregiving trajectory and more
      culturally sensitive strategies, particularly indirect methods, for working with
      diverse populations of caregivers.

PMID- 22150178
TI  - Cultural vulnerability and professional narratives.
AB  - In this article the author draws upon research with palliative care professionals
      in the United Kingdom to discuss the value of a stance of cultural vulnerability
      in intercultural care. Cultural vulnerability recognizes the reality, but also
      the ethical value of uncertainty and not-knowing in care. Attentiveness to
      professional narratives is advocated as vital in the development of greater
      understanding of cultural vulnerability and its effects. The role of cultural
      identifications and the politics of racism in social work narratives is given
      specific attention.

PMID- 22150179
TI  - The assimilation of problematic experiences sequence: an approach to evidence
      based practice in bereavement counseling.
AB  - Current theories of bereavement are available and complex and suggest that for
      the bereaved there is no single pathway through grief. This challenges ethically
      motivated bereavement counselors to integrate theory into evidence-based
      practice. The Assimilation of Problematic Experiences Sequence offers a way
      forward for evaluating the effectiveness of bereavement counseling. Parallels are
      drawn between grief as disrupted self-narrative and grief as the dissociated
      voices of unassimilated experience. This assimilation sequence is proposed as a
      means of tracking psychological change in bereaved clients.

PMID- 22150180
TI  - Surviving critical illness: a case study in ambiguity.
AB  - Social workers address issues of critical illness and end of life in multiple
      settings. Due to advances in medical technology, an increasing number of patients
      survive severe critical illnesses. Little is known about the psychological
      dynamics of these patients who recover from critical illness and move into the
      liminal space between life and death. In this article the author analyzes the
      psychological ambiguities present during recovery from critical illness. Using a
      case study, connections will be made between surviving critical illness and the
      theoretical constructs of liminality, illness narratives, ambiguous dying, and
      ambiguous loss. Practice applications for social workers are addressed.

PMID- 22150181
TI  - Interdisciplinary perceptions of the social work role in hospice: building upon
      the classic Kulys and Davis study.
AB  - This national survey found that hospice directors (n = 43) considered social
      workers most qualified, and most involved, in 12 of 24 interventions considered
      by social workers to define their role. This is a change from Kulys and Davis' (
      1986 ,  1987 ) findings of a more limited social work role in hospice. The
      results of the current study provide new information about director attitudes,
      social work involvement, and the impact of efforts to develop the hospice social
      work field. Social work education should incorporate more end-of-life care
      content to continue this progress, and hospice social workers should continue to
      document their effectiveness on the hospice team.

PMID- 22150186
TI  - The State of the Science 2012: building blocks for the future.

PMID- 22150187
TI  - Medical education, social accountability and patient outcomes.

PMID- 22150188
TI  - Purposeful assessment.

PMID- 22150189
TI  - Layers within layers ... self-regulation in a complex learning environment.

PMID- 22150190
TI  - To every complex problem there is a simple solution...

PMID- 22150191
TI  - Lifelong quality improvement.

PMID- 22150192
TI  - Educators must consider patient outcomes when assessing the impact of clinical
      training.
AB  - CONTEXT: The concept of outcomes has been used in health care for over 140 years.
      The use of outcomes in assessing quality of care regained prominence in the 1960s
      based on Donabedian's framework of structures, processes and outcomes. In the
      1990s, the use of outcomes in medical education gained great favour, although the
      outcomes used were not carefully defined. Recently, a debate has ensued about the
      costs and, thus, sustainability of current health care programmes, focusing on
      the (non-)necessity of services, missed prevention opportunities and the
      efficiency of treatment programmes. Measurements using education outcomes and
      health care outcomes must take these issues into account, preferably from a
      common framework. As health care becomes increasingly costly and even
      inefficient, issues of effectiveness are often neglected in policy making.
      METHODS: This paper uses peer-reviewed evidence and an outcomes framework to
      explore the implications of current realities for the makers of education policy
      in the health professions and for the staff who train health professionals.
      DISCUSSION: If the ultimate impacts of practices and policies in health
      professions education are not considered, how will we know if our education
      structures, processes and outcomes are optimal? This essay examines this question
      from the perspectives of three related issues. The first refers to the need for a
      common framework if the outcomes of patient and community care are to be
      evaluated properly. The second perspective refers to whether it is feasible to
      consider both patient-based outcomes and patient-reported outcomes in assessing
      the impact of education programmes, especially at more advanced levels of
      training. The third perspective concerns the challenges and limitations that may
      be encountered in focusing on patient outcomes as a measure of the impact of
      education. The concluding discussion suggests how the results of such longer-term
      impact studies should be interpreted as key validity checks on the quality and
      effectiveness of medical education and clinical education if we are to address
      the validity and efficiency of outcomes used in education and training.

PMID- 22150193
TI  - Seeking impact of medical schools on health: meeting the challenges of social
      accountability.
AB  - CONTEXT: The acquisition of sums of knowledge and mastery of sophisticated
      technologies by medical graduates is insufficient for their responsibilities to
      recognise and adapt to people's evolving needs. RESPONSE: A Global Consensus on
      Social Accountability for Medical Schools brought together 130 organisations and
      individuals from around the world with responsibility for health education,
      professional regulation and policy making to participate for 8 months in a three
      round Delphi process leading to a 3-day consensus development conference which
      included weighted representation from all regions of the world. The resulting
      Consensus reflects agreement on 10 strategic directions to enable a medical
      school to be socially accountable. RESULTS: The list of 10 directions embraces a
      system-wide scope from identification of health needs to verification of the
      effects of medical schools on those needs, all driven by the quest for positive
      impact on peoples' health status. This includes an understanding of the social
      context, an identification of health challenges and needs and the creation of
      relationships to act efficiently (directions 1 and 2). Within the spectrum of the
      health workforce required to address health needs, the anticipated role and
      competences of the doctor are described (direction 3) serving as a guide to the
      education strategy (direction 4), which the medical school is called to implement
      along with consistent research and service strategies (direction 5). Standards
      are required to steer the institution towards a high level of excellence
      (directions 6 and 7), which national authorities need to recognise (direction 8).
      While social accountability is a universal value (direction 9), local societies
      will be the ultimate appraisers of the achievements of the school and its
      graduates (direction 10).

PMID- 22150194
TI  - Making sense of work-based assessment: ask the right questions, in the right way,
      about the right things, of the right people.
AB  - CONTEXT: Historically, assessments have often measured the measurable rather than
      the important. Over the last 30 years, however, we have witnessed a gradual shift
      of focus in medical education. We now attempt to teach and assess what matters
      most. In addition, the component parts of a competence must be marshalled
      together and integrated to deal with real workplace problems. Workplace-based
      assessment (WBA) is complex, and has relied on a number of recently developed
      methods and instruments, of which some involve checklists and others use
      judgements made on rating scales. Given that judgements are subjective, how can
      we optimise their validity and reliability? METHODS: This paper gleans
      psychometric data from a range of evaluations in order to highlight features of
      judgement-based assessments that are associated with better validity and
      reliability. It offers some issues for discussion and research around WBA. It
      refers to literature in a selective way. It does not purport to represent a
      systematic review, but it does attempt to offer some serious analyses of why some
      observations occur in studies of WBA and what we need to do about them. RESULTS
      AND DISCUSSION: Four general principles emerge: the response scale should be
      aligned to the reality map of the judges; judgements rather than objective
      observations should be sought; the assessment should focus on competencies that
      are central to the activity observed, and the assessors who are best-placed to
      judge performance should be asked to participate.

PMID- 22150195
TI  - Programmatic assessment and Kane's validity perspective.
AB  - CONTEXT: Programmatic assessment is a notion that implies that the strength of
      the assessment process results from a careful combination of various assessment
      instruments. Accordingly, no single instrument is superior to another, but each
      has its own strengths, weaknesses and purpose in a programme. Yet, in terms of
      psychometric methods, a one-size-fits-all approach is often used. Kane's views on
      validity as represented by a series of arguments provide a useful framework from
      which to highlight the value of different widely used approaches to improve the
      quality and validity of assessment procedures. METHODS: In this paper we discuss
      four inferences which form part of Kane's validity theory: from observations to
      scores; from scores to universe scores; from universe scores to target domain,
      and from target domain to construct. For each of these inferences, we provide
      examples and descriptions of approaches and arguments that may help to support
      the validity inference. CONCLUSIONS: As well as standard psychometric methods, a
      programme of assessment makes use of various other arguments, such as: item
      review and quality control, structuring and examiner training; probabilistic
      methods, saturation approaches and judgement processes, and epidemiological
      methods, collation, triangulation and member-checking procedures. In an
      assessment programme each of these can be used.

PMID- 22150196
TI  - History and practice of competency-based assessment.
AB  - CONTEXT: In response to historical trends in expectations of doctors, the goals
      of medical education are increasingly framed in terms of global competencies. The
      language of these competencies has tended to adopt a prescriptive, rather than
      descriptive, approach. However, despite widespread agreement on the importance of
      competency-based education and more than two decades of study, this effort has
      not generated a dependable set of assessment tools. DISCUSSION: Because models of
      competency are legislated, rather than shaped by scholarly consideration of
      empirical data, it is unlikely that such models directly reflect actual human
      behaviour. Efforts to measure clinical behaviours could benefit from increased
      clarity in three related conceptual areas. Firstly, the language of educational
      constructs should be framed in terms of data-based hypotheses, rather than in
      terms of intuitively plausible abilities. Secondly, these constructs should be
      specified in terms of the situations to which they are relevant, rather than as
      global personal characteristics. Finally, the resources required to measure these
      constructs should be rigorously established because a common resource-based
      metric would allow for rational selection of assessment methods. Specific methods
      to establish each of these objectives are discussed. CONCLUSIONS: The political
      process of negotiating educational objectives should not be confused with the
      scientific work of establishing coherent and interpretable patterns of behaviour.
      Although the two activities can complement one another, each has its own distinct
      methods and style of discourse. It is thus critical to maintain boundaries
      between these two approaches to defining professional performance.

PMID- 22150197
TI  - Interprofessional education: a review of context, learning and the research
      agenda.
AB  - CONTEXT: Interprofessional education (IPE) is not a recent phenomenon and has
      been the subject of several World Health Organization reports. Its focus is on
      health professionals and students learning with, from and about one another to
      improve collaboration and the quality of patient care. The drivers for IPE
      include new models of health care delivery in the context of an ageing population
      and the increasing prevalence of long-term chronic disease, in addition to the
      patient safety agenda. The delivery of complex health care requires a team-based
      and collaborative approach, although teamwork and collaborative practice are not
      necessarily synonymous. The rationale for IPE is that learning together enhances
      future working together. DISCUSSION: Systematic reviews of IPE have shown some
      evidence that IPE fosters positive interaction among different professions and
      variable evidence that it improves attitudes towards other professionals.
      Generalisation across published papers is difficult because IPE initiatives are
      diverse and good evaluation methodology and data are lacking. In terms of
      constructive alignment from an education viewpoint, there is a need for educators
      to define learning outcomes and match these with learning activities to ensure
      that IPE demonstrates added value over uniprofessional learning. Assessment is
      difficult as pre-qualification professional education focuses on the individual
      and professional accreditation organisations mandate only for their own
      professions. CONCLUSIONS: Interprofessional education draws from a number of
      education, sociology and psychology theories, and these are briefly discussed.
      The most pressing research questions for the IPE community are defined and the
      challenges for IPE explored.

PMID- 22150198
TI  - A reflective analysis of medical education research on self-regulation in
      learning and practice.
AB  - OBJECTIVES: In the health professions we expect practitioners and trainees to
      engage in self-regulation of their learning and practice. For example, doctors
      are responsible for diagnosing their own learning needs and pursuing professional
      development opportunities; medical residents are expected to identify what they
      do not know when caring for patients and to seek help from supervisors when they
      need it, and medical school curricula are increasingly called upon to support
      self-regulation as a central learning outcome. Given the importance of self
      regulation in both health professions education and ongoing professional
      practice, our aim was to generate a snapshot of the state of the science in
      medical education research in this area. METHODS: To achieve this goal, we
      gathered literature focused on self-regulation or self-directed learning
      undertaken from multiple perspectives. Then, with support from a multi-component
      theoretical framework, we created an overarching map of the themes addressed thus
      far and emerging findings. We built from that integrative overview to consider
      contributions, connections and gaps in research on self-regulation to date.
      RESULTS AND CONCLUSIONS: Based on this reflective analysis, we conclude that the
      medical education community's understanding about self-regulation will continue
      to advance as we: (i) consider how learning is undertaken within the complex
      social contexts of clinical training and practice; (ii) think of self-regulation
      within an integrative perspective that allows us to combine disparate strands of
      research and to consider self-regulation across the training continuum in
      medicine, from learning to practice; (iii) attend to the grain size of analysis
      both thoughtfully and intentionally, and (iv) most essentially, extend our
      efforts to understand the need for and best practices in support of self
      regulation.

PMID- 22150199
TI  - Helping medical learners recognise and manage unconscious bias toward certain
      patient groups.
AB  - CONTEXT: For the last 30 years, developments in cognitive sciences have
      demonstrated that human behaviour, beliefs and attitudes are shaped by automatic
      and unconscious cognitive processes. Only recently has much attention been paid
      to how unconscious biases based on certain patient characteristics may: (i)
      result in behaviour that is preferential toward or against specific patients;
      (ii) influence treatment decisions, and (iii) adversely influence the patient
      doctor relationship. Partly in response to accreditation requirements, medical
      educators are now exploring how they might help students and residents to develop
      awareness of their own potential biases and strategies to mitigate them. METHODS:
      In this paper, we briefly review key cognition concepts and describe the limited
      published literature about educational strategies for addressing unconscious
      bias. DISCUSSION: We propose a developmental model to illustrate how individuals
      might move from absolute denial of unconscious bias to the integration of
      strategies to mitigate its influence on their interactions with patients and
      offer recommendations to educators and education researchers.

PMID- 22150200
TI  - Realist methods in medical education research: what are they and what can they
      contribute?
AB  - CONTEXT: Education is a complex intervention which produces different outcomes in
      different circumstances. Education researchers have long recognised the need to
      supplement experimental studies of efficacy with a broader range of study designs
      that will help to unpack the 'how' and 'why' questions and illuminate the many,
      varied and interdependent mechanisms by which interventions may work (or fail to
      work) in different contexts. METHODS: One promising approach is realist
      evaluation, which seeks to establish what works, for whom, in what circumstances,
      in what respects, to what extent, and why. This paper introduces the realist
      approach and explains why it is particularly suited to education research. It
      gives a brief introduction to the philosophical assumptions underlying realist
      methods and outlines key principles of realist evaluation (designed for empirical
      studies) and realist review (the application of realist methods to secondary
      research). DISCUSSION: The paper warns that realist approaches are not a panacea
      and lists the circumstances in which they are likely to be particularly useful.

PMID- 22150201
TI  - Kirkpatrick's levels and education 'evidence'.
AB  - OBJECTIVES: This study aims to review, critically, the suitability of
      Kirkpatrick's levels for appraising interventions in medical education, to review
      empirical evidence of their application in this context, and to explore
      alternative ways of appraising research evidence. METHODS: The mixed methods used
      in this research included a narrative literature review, a critical review of
      theory and qualitative empirical analysis, conducted within a process of
      cooperative inquiry. RESULTS: Kirkpatrick's levels, introduced to evaluate
      training in industry, involve so many implicit assumptions that they are suitable
      for use only in relatively simple instructional designs, short-term endpoints and
      beneficiaries other than learners. Such conditions are met by perhaps one-fifth
      of medical education evidence reviews. Under other conditions, the hierarchical
      application of the levels as a critical appraisal tool adds little value and
      leaves reviewers to make global judgements of the trustworthiness of the data.
      CONCLUSIONS: Far from defining a reference standard critical appraisal tool, this
      research shows that 'quality' is defined as much by the purpose to which evidence
      is to be put as by any invariant and objectively measurable quality. Pending
      further research, we offer a simple way of deciding how to appraise the quality
      of medical education research.

PMID- 22150202
TI  - Quality improvement in medical education: current state and future directions.
AB  - CONTEXT: During the last decade, there has been a drive to improve the quality of
      patient care and prevent the occurrence of avoidable errors. This review
      describes current efforts to teach or engage trainees in patient safety and
      quality improvement (QI), summarises progress to date, as well as successes and
      challenges, and lists our recommendations for the next steps that will shape the
      future of patient safety and QI in medical education. CURRENT STATUS: Trainees
      encounter patient safety and QI through three main groups of activity. First are
      formal curricula that teach concepts or methods intended to facilitate trainees'
      participation in QI activities. These curricula increase learner knowledge and
      may improve clinical processes, but demonstrate limited capacity to modify
      learner behaviours. Second are educational activities that impart specific skills
      related to safety or quality which are considered to represent core doctor
      competencies (e.g. effective patient handover). These are frequently taught
      effectively, but without emphasis on the general safety or quality principles
      that inform the relevant skills. Third are real-life QI initiatives that involve
      trainees as active or passive participants. These innovative approaches expose
      trainees to safety and quality by integrating QI activities into trainees' day-to
      day work. However, this integration can be challenging and can sometimes result
      in tension with broader educational goals. FUTURE DIRECTIONS: To prepare the next
      generation of doctors to make meaningful contributions to the quality mission, we
      propose the following call to action. Firstly, a major effort to build faculty
      capacity, especially among teachers of QI, should be instigated. Secondly,
      accreditation standards and assessment methods, both during training and at end
      of-training certification examinations, should explicitly target these
      competencies. Finally, and perhaps most importantly, we must refocus our
      attention at all levels of training and instil fundamental, collaborative, open
      minded behaviours so that future clinicians are primed to promote a culture of
      safer, higher-quality care.

PMID- 22150203
TI  - Generic skills in medical education: developing the tools for successful lifelong
      learning.
AB  - CONTEXT: Higher education has invested in defining the role of generic skills in
      developing effective, adaptable graduates fit for a changing workplace. Research
      confirms that the development of generic skills that underpin effectiveness and
      adaptability in graduates is highly context-dependent and is shaped by the
      discipline within which these skills are conceptualised, valued and taught. This
      places the responsibility for generic skills enhancement clearly within the remit
      of global medical education. IMPLICATIONS: Many factors will influence the skill
      set with which students begin their medical training and experience at entry
      needs to be taken into account. Learning and teaching environments enhance
      effective skill development through active learning, teaching for understanding,
      feedback, and teacher-student and student-student interaction. Medical curricula
      need to provide students with opportunities to practise and develop their generic
      skills in a range of discipline-specific contexts. Curricular design should
      include explicit and integrated generic skills objectives against which students'
      progress can be monitored. Assessment and feedback serve as valuable
      reinforcements of the professed importance of generic skills to both learner and
      teacher, and will encourage students to self-evaluate and take responsibility for
      their own skill development. The continual need for students to modify their
      practice in response to changes in their environment and the requirements of
      their roles will help students to develop the ability to transfer these skills at
      transition points in their training and future careers. CONCLUSIONS: If they are
      to take their place in an ever-changing profession, medical students need to be
      competent in the skills that underpin lifelong learning. Only then will the
      doctors of the future be well placed to adapt to changes in knowledge, update
      their practice in line with the changing evidence base, and continue to
      contribute effectively as societal needs change.

PMID- 22150204
TI  - An Italian retrospective study on the routine clinical use of low-dose
      alemtuzumab in relapsed/refractory chronic lymphocytic leukaemia patients.
AB  - Low-dose alemtuzumab has shown a favourable toxicity profile coupled with good
      results in terms of efficacy in relapsed/refractory chronic lymphocytic leukaemia
      (CLL). We conducted a multicentre retrospective study on the routine clinical use
      of low-dose alemtuzumab in this patient setting. One hundred and eight
      relapsed/refractory CLL patients from 11 Italian centres were included in the
      analysis. All patients had an Eastern Cooperative Oncology Group performance
      status <=2 and the majority (84%) had adenopathies <5 cm. Low-dose alemtuzumab
      was defined as a total weekly dose <=45 mg and a cumulative dose <=600 mg given
      for up to 18 weeks. The overall response rate was 56% (22% complete remissions).
      After a median follow-up of 42.2 months, the median overall survival and
      progression-free survival were 39.0 and 19.4 months, respectively. In univariate
      analysis, response was inversely associated with lymph node (P = 0.01) and spleen
      (P = 0.02) size, fludarabine-refractoriness (P = 0.01) and del(11q) (P = 0.009).
      Advanced age and del(17p) were not associated with a worse outcome. Cumulative
      dose of alemtuzumab was not associated to response. Toxicities were usually mild
      and manageable; severe infections occurred in seven patients (7%) during therapy.
      This retrospective analysis confirms that low-dose alemtuzumab is a valid and
      currently used therapeutic option for the treatment of relapsed/refractory CLL.

PMID- 22150206
TI  - Responses of Lucilia sericata Meigen (Diptera: Calliphoridae) to cadaveric
      volatile organic compounds.
AB  - Flies of the Calliphoridae Family are the most forensically important insects
      because of their abundance on the decedent during the first minutes following
      death. Necrophagous insects are attracted at a distance by a decomposing body,
      through the use of volatile chemical cues. We tested the possible attractive role
      of some volatile organic chemicals (VOCs) released by decaying cadavers, on male
      and female of Lucilia sericata Meigen (Diptera: Calliphoridae). Two complementary
      approaches were used. Electroantennography (EAG) allowed identifying the
      semiochemicals that are detected by the olfactory system of L. sericata. Dose
      response tests with EAG showed that dimethyl disulfide (DMDS) and butan-1-ol
      elicited the highest responses. Behavioral assays showed that, among the VOCs
      tested, DMDS and butan-1-ol are attractive for L. sericata, while the other VOCs
      are repulsive or do not cause any behavior. Our results may have potential
      implications in a better understanding of attractiveness of blowflies toward a
      corpse.

PMID- 22150208
TI  - Three-step electrocardiographic evaluation of cardiac resynchronization.

PMID- 22150207
TI  - Predicting 14-day mortality after severe traumatic brain injury: application of
      the IMPACT models in the brain trauma foundation TBI-trac(r) New York State
      database.
AB  - Prognostic models for outcome prediction in patients with traumatic brain injury
      (TBI) are important instruments in both clinical practice and research. To remain
      current a continuous process of model validation is necessary. We aimed to
      investigate the performance of the International Mission on Prognosis and
      Analysis of Clinical Trials in TBI (IMPACT) prognostic models in predicting
      mortality in a contemporary New York State TBI registry developed and maintained
      by the Brain Trauma Foundation. The Brain Trauma Foundation (BTF) TBI-trac(r)
      database contains data on 3125 patients who sustained severe TBI (Glasgow Coma
      Scale [GCS] score <= 8) in New York State between 2000 and 2009. The outcome
      measure was 14-day mortality. To predict 14-day mortality with admission data, we
      adapted the IMPACT Core and Extended models. Performance of the models was
      assessed by determining calibration (agreement between observed and predicted
      outcomes), and discrimination (separation of those patients who die from those
      who survive). Calibration was explored graphically with calibration plots.
      Discrimination was expressed by the area under the receiver operating
      characteristic (ROC) curve (AUC). A total of 2513 out of 3125 patients in the BTF
      database met the inclusion criteria. The 14-day mortality rate was 23%. The
      models showed excellent calibration. Mean predicted probabilities were 20% for
      the Core model and 24% for the Extended model. Both models showed good
      discrimination with AUCs of 0.79 (Core) and 0.83 (Extended). We conclude that the
      IMPACT models validly predict 14-day mortality in the BTF database, confirming
      generalizability of these models for outcome prediction in TBI patients.

PMID- 22150210
TI  - Short-term fluctuations of sugar beet damping-off by Pythium ultimum in relation
      to changes in bacterial communities after organic amendments to two soils.
AB  - Previously, oscillations in beet seedling damping-off by Pythium ultimum,
      measured as area under the disease progress curve (AUDPC), were demonstrated
      after incorporation of organic materials into organic and conventional soils.
      These periodic fluctuations of P. ultimum infections were cross-correlated with
      oscillations of copiotrophic CFU at lags of 2 to 4 days. For this article, we
      investigated whether bacterial communities and microbial activities fluctuated
      after a disturbance from incorporation of organic materials, and whether these
      fluctuations were linked to the short-term oscillations in AUDPC of beet seedling
      damping-off and bacterial populations (CFU) in soil. Soil microbial communities
      studied by polymerase chain reaction-DGGE analysis of 16S DNA after isolation of
      total DNA from soil and microbial activities measured as CO(2) emission rates
      were monitored daily for 14 days after addition of grass-clover (GC) or composted
      manure (CM) into organic versus conventional soils. Similar to our previous
      findings, AUDPC and density of copiotrophic bacteria oscillated with time.
      Fluctuations in species richness (S), Shannon diversity index (H), and individual
      amplicons on DGGE gels were also detected. Oscillations in AUDPC were positively
      cross-correlated with copiotrophic CFU in all soils. Oscillations in AUDPC were
      also positively cross-correlated with 19 to 35% of the high-intensity DNA
      fragments in soils amended with GC but only 2 to 3% of these fragments in CM
      amended soils. AUDPC values were negatively cross-correlated with 13 to 17% of
      the amplicons with low average intensities in CM-amended soils, which were not
      correlated with densities of copiotrophic CFU. CO(2) emission rates had
      remarkable variations in the initial 7 days after either of the soil amendments
      but were not associated with daily changes in AUDPC. The results suggest that
      infection by P. ultimum is hampered by competition from culturable copiotrophic
      bacteria and some high-intensity DGGE amplicons, because AUDPC is cross
      correlated with these variables at lags of 1 to 4 days. However, negative cross
      correlations with low-intensity DNA fragments indicate that P. ultimum infection
      could also be suppressed by antagonistic bacteria with low densities that may be
      nonculturable species, especially in CM amended soil. The organic soil generally
      had lower AUDPC values, higher bacterial diversity, and negative cross
      correlations between AUDPC and low-intensity DNA fragments (after CM amendment),
      indicating that specific bacteria that do not attain high densities may
      contribute to P. ultimum suppression in organic soils.

PMID- 22150209
TI  - Extended practice and aerobic exercise interventions benefit untrained cognitive
      outcomes in older adults: a meta-analysis.
AB  - OBJECTIVES: To examine whether therapeutic interventions of extended practice of
      cognitive tasks or aerobic exercise have led to significant improvement in
      untrained cognitive tasks. DESIGN: The PSYCINFO, MEDLINE, and Abstracts in Social
      Gerontology databases were searched for English-language studies of cognitive
      interventions of exercise or extended cognitive practice between 1966 and 2010.
      The final search was in January 2011. Studies included were experimental
      interventions hypothesizing improvement on untrained cognitive outcomes with pre-
      and posttests. Studies of varying quality were included and compared. SETTING:
      Interventions generally took place in laboratories, in gymnasium facilities, in
      the home, and outdoors. Experimenters administered testing. PARTICIPANTS: Forty
      two studies with 3,781 healthy older adults aged 55 and older were analyzed.
      MEASUREMENTS: Between-group effect sizes (ESs), which account for practice
      effects on outcome measures, and within-experimental group ESs were computed from
      untrained cognitive outcome domains, including choice reaction time, memory, and
      executive function, and compared. ESs were also coded for training type and study
      quality. Multilevel mixed-effect analyses accommodated multiple outcomes from
      individual studies. RESULTS: Extended practice (estimated ES = 0.33, 95%
      confidence interval (CI) = 0.13-0.52) and aerobic fitness (estimated ES = 0.33,
      95% CI = 0.10-0.55) training produced significant between-group ESs, but they did
      not differ in magnitude. Better study quality was associated with larger ESs.
      CONCLUSION: Findings indicate that aerobic and extended cognitive practice
      training interventions for healthy older adults improve performance on untrained
      cognitive tasks.

PMID- 22150211
TI  - Stimulation of thaumarchaeal ammonia oxidation by ammonia derived from organic
      nitrogen but not added inorganic nitrogen.
AB  - Ammonia oxidation, the first step in nitrification, is performed by autotrophic
      bacteria and thaumarchaea, whose relative contributions vary in different soils.
      Distinctive environmental niches for the two groups have not been identified, but
      evidence from previous studies suggests that activity of thaumarchaea, unlike
      that of bacterial ammonia oxidizers, is unaffected by addition of inorganic N
      fertilizer and that they preferentially utilize ammonia generated from the
      mineralization of organic N. This hypothesis was tested by determining the
      influence of both inorganic and organic N sources on nitrification rate and
      ammonia oxidizer growth and community structure in microcosms containing acidic,
      forest soil in which ammonia oxidation was dominated by thaumarchaea.
      Nitrification rate was unaffected by the incubation of soil with inorganic
      ammonium but was significantly stimulated by the addition of organic N. Oxidation
      of ammonia generated from native soil organic matter or added organic N, but not
      added inorganic N, was accompanied by increases in abundance of the thaumarchaeal
      amoA gene, a functional gene for ammonia oxidation, but changes in community
      structure were not observed. Bacterial amoA genes could not be detected. Ammonia
      oxidation was completely inhibited by 0.01% acetylene in all treatments,
      indicating ammonia monooxygenase-dependent activity. The findings have
      implications for current models of soil nitrification and for nitrification
      control strategies to minimize fertilizer loss and nitrous oxide production.

PMID- 22150213
TI  - Mammography screening behaviors of women exposed prenatally to
      diethylstilbestrol.
AB  - BACKGROUND: In utero diethylstilbestrol (DES) exposure is a risk factor for rare
      development of vaginal and cervical cancer and may potentially be a risk factor
      for breast cancer. Mammography use in this population is relatively unknown;
      therefore, this study aims to determine if in utero DES exposure is associated
      with the frequency of mammography screening examinations while considering
      demographic and clinical factors. METHODS: Using combined DES cohort
      questionnaire data, self-reported mammography screening over the past 5 years
      (2001-2006) was analyzed in women aged >=45 years. Binary logistic regression
      assessed if DES exposure was associated with mammography use after adjustment for
      benign breast disease (BBD), previous cancer diagnosis, and whether insurance
      access influenced screening use. RESULTS: Overall, the frequency of mammography
      examinations was similar for both DES-exposed and unexposed women. DES-exposed
      (n=2986) and unexposed women (n=1397) over the age of 44 reported receiving >=3
      mammography examinations in the past 5 years (73.8% and 74.0%, respectively).
      After adjustment, DES exposure was not associated with >=3 mammograms in the past
      5 years compared to <=2 examinations (odds ratio [OR] 1.00, 95% confidence
      interval [CI] 0.86-1.17), p=0.99). CONCLUSIONS: In utero DES exposure was not
      associated with mammography use, nor was health insurance status or a BBD or
      cancer diagnosis. Because of the potential elevated risk for breast cancer in
      women exposed prenatally to DES, continued monitoring of standard mammography
      recommendations is recommended for this group, which is predominantly over the
      age of 45.

PMID- 22150223
TI  - A molten globule-to-ordered structure transition of Drosophila melanogaster
      crammer is required for its ability to inhibit cathepsin.
AB  - Drosophila melanogaster crammer is a novel cathepsin inhibitor that is involved
      in LTM (long-term memory) formation. The mechanism by which the inhibitory
      activity is regulated remains unclear. In the present paper we have shown that
      the oligomeric state of crammer is pH dependent. At neutral pH, crammer is
      predominantly dimeric in vitro as a result of disulfide bond formation, and is
      monomeric at acidic pH. Our inhibition assay shows that monomeric crammer, not
      disulfide-bonded dimer, is a strong competitive inhibitor of cathepsin L. Crammer
      is a monomeric molten globule in acidic solution, a condition that is similar to
      the environment in the lysosome where crammer is probably located. Upon binding
      to cathepsin L, however, crammer undergoes a molten globule-to-ordered structural
      transition. Using high-resolution NMR spectroscopy, we have shown that a cysteine
      to-serine point mutation at position 72 (C72S) renders crammer monomeric at pH
      6.0 and that the structure of the C72S variant highly resembles that of wild-type
      crammer in complex with cathepsin L at pH 4.0. We have determined the first
      solution structure of propeptide-like protease inhibitor in its active form and
      examined in detail using a variety of spectroscopic methods the folding
      properties of crammer in order to delineate its biomolecular recognition of
      cathepsin.

PMID- 22150225
TI  - Regulation of MMP3 by laminin alpha 4 in human osteoarthritic cartilage.

PMID- 22150224
TI  - Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage
      following stroke in Type 2 diabetic rats.
AB  - Diabetes is a strong risk factor for premature and severe stroke. The GLP-1R
      (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the
      treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects.
      The aim of the present study was to determine the efficacy of Ex-4 against stroke
      in diabetes by using a diabetic animal model, a drug administration paradigm and
      a dose that mimics a diabetic patient on Ex-4 therapy. Furthermore, we
      investigated inflammation and neurogenesis as potential cellular mechanisms
      underlying the Ex-4 efficacy. A total of seven 9-month-old Type 2 diabetic Goto
      Kakizaki rats were treated peripherally for 4 weeks with Ex-4 at 0.1, 1 or 5
      MUg/kg of body weight before inducing stroke by transient middle cerebral artery
      occlusion and for 2-4 weeks thereafter. The severity of ischaemic damage was
      measured by evaluation of stroke volume and by stereological counting of neurons
      in the striatum and cortex. We also quantitatively evaluated stroke-induced
      inflammation, stem cell proliferation and neurogenesis. We show a profound anti
      stroke efficacy of the clinical dose of Ex-4 in diabetic rats, an arrested
      microglia infiltration and an increase of stroke-induced neural stem cell
      proliferation and neuroblast formation, while stroke-induced neurogenesis was not
      affected by Ex-4. The results show a pronounced anti-stroke, neuroprotective and
      anti-inflammatory effect of peripheral and chronic Ex-4 treatment in middle-aged
      diabetic animals in a preclinical setting that has the potential to mimic the
      clinical treatment. Our results should provide strong impetus to further
      investigate GLP-1R agonists for their neuroprotective action in diabetes, and for
      their possible use as anti-stroke medication in non-diabetic conditions.

PMID- 22150226
TI  - Small RNAs and transposon silencing in plants.
AB  - Transposons are highly conserved in plants and have created a symbiotic
      relationship with the host genome. An important factor of the successful
      communication between transposons and host plants is epigenetic modifications
      including DNA methylation and the modifications of the histone tail. In plants,
      small interfering RNAs (siRNAs) are responsible for RNA-directed DNA methylation
      (RdDM) that suppresses transposon activities. Although most transposons are
      silent in their host plants, certain genomic shocks, such as an environmental
      stress or a hybridization event, might trigger transposon activation. Further,
      since transposons can affect the regulation mechanisms of host genes, it is
      possible that transposons have co-evolved as an important mechanism for plant
      development and adaptation. Recent new findings reveal that siRNAs control not
      only transcriptional activation, but also suppress transgenerational
      transposition of mobile elements making siRNAs critically important towards
      maintaining genome stability. Together these data suggest host-mediated siRNA
      regulation of transposons appears to have been adapted for controlling essential
      systems of plant development, morphogenesis, and reproduction.

PMID- 22150227
TI  - Mixed testicular atrophy related to atherosclerosis: first lessons from the ApoE(
      /-)/ LDL receptor(-/-) double knockout mouse model.
AB  - Age-related testicular changes are associated with declining spermatogenesis and
      testosterone levels. A relationship to atherosclerosis has never been
      investigated systematically. The ApoE(-/-)/LDL receptor(-/-) double knockout
      mouse model, providing a remarkable homology to human atherosclerosis, is an
      ideal tool to investigate spermatogenetic alterations in this context. Testes (n
      = 10) from ApoE(-/-)/LDL receptor(-/-) double knockout mice at the age of 80
      weeks were perfused in vivo with contrast agent, harvested and scanned with micro
      CT at (4.9 MUm3) voxel size. Testes (n = 8) of C57/BL mice at the same age served
      as controls. Testis volume (mm3) and total vascular volume fraction (mm3) were
      quantified using micro-CT. Serum testosterone levels were determined. Testicular
      histology and epididymal sections were analysed for tubular structure,
      spermatogenetic scores and sperm count. The expression of protamine 2 as a marker
      for elongated spermatids, inflammation markers (CD4, F4/80) and hypoxia inducible
      factor 1 alpha (HIF1 alpha) were investigated using immunohistochemistry. ApoE(-/
      )/LDL receptor(-/-) double knockout mice exhibit diminished testis and vascular
      volume fraction with respect to that of controls (p < 0.001). These findings were
      associated with a reduction of testosterone levels (p < 0.001). Mixed atrophy was
      present in 41% of the seminiferous tubuli in ApoE(-/-)/LDL receptor(-/-) double
      knockout mice at the age of 80 weeks. Sperm counts from the epididymis
      demonstrated a significant decrease in ApoE(-/-)/LDL receptor(-/-) double
      knockout mice (p < 0.001). In addition, sperm specific protamine 2 expression was
      decreased in testicular tissue and epididymis of ApoE(-/-)/LDL receptor(-/-)
      double knockout mice compared with that of control mice. Peritubular inflammatory
      infiltration and the expression of the hypoxia related marker was observed. Mixed
      testicular atrophy in ApoE(-/-)/LDL receptor(-/-) double knockout mice is linked
      to reduced testis volume, vascular volume fraction and low testosterone serum
      levels, suggesting a direct relation between atherosclerosis and disturbed
      spermatogenesis.

PMID- 22150228
TI  - Deletion of yncD gene in Salmonella enterica ssp. enterica serovar Typhi leads to
      attenuation in mouse model.
AB  - TonB-dependent transporters (TBDTs) are bacterial outer membrane proteins that
      are usually involved in the uptake of certain key nutrients, for example iron. In
      the genome of Salmonella enterica ssp. enterica serovar Typhi, the yncD gene
      encodes a putative TBDT and was identified recently as an in vivo-induced
      antigen. In the present study, a yncD-deleted mutant was constructed to evaluate
      the role of the yncD gene in virulence. Our results showed that the mutant is
      attenuated in a mouse model by intraperitoneal injection and its virulence is
      restored by the transformation of a complement plasmid. The competition
      experiments showed that the survival ability of the yncD-deleted mutant decreases
      significantly in vivo. To evaluate its vaccine potential, the yncD-deleted mutant
      was inoculated intranasally in the mouse model. The findings demonstrated a
      significant immunoprotection against the lethal wild-type challenge. The
      regulation analysis showed that yncD gene promoter is upregulated under acidic
      condition. The present study demonstrates that the yncD gene plays an important
      role in bacterial survival inside the host and is suitable for the construction
      of attenuated vaccine strains as a candidate target gene.

PMID- 22150229
TI  - Intralesional phosphatidylcholine and sodium deoxycholate: a possible treatment
      option for nevus lipomatosus superficialis.
AB  - Treatment options are limited for classic nevus lipomatosus superficialis, in
      which clustered lesions present over a large area. We present a case of nevus
      lipomatosus superficialis that showed clinical and histological improvement after
      treatment with intralesional phosphatidylcholine and sodium deoxy-cholate.

PMID- 22150230
TI  - A hole in our thinking: a response to Scambler's 'Health inequalities'.

PMID- 22150231
TI  - Genetic evidence for natural product-mediated plant-plant allelopathy in rice
      (Oryza sativa).
AB  - * There is controversy as to whether specific natural products play a role in
      directly mediating antagonistic plant-plant interactions - that is, allelopathy.
      If proved to exist, such phenomena would hold considerable promise for agronomic
      improvement of staple food crops such as rice (Oryza sativa). * However, while
      substantiated by the presence of phytotoxic compounds at potentially relevant
      concentrations, demonstrating a direct role for specific natural products in
      allelopathy has been difficult because of the chemical complexity of root and
      plant litter exudates. This complexity can be bypassed via selective genetic
      manipulation to ablate production of putative allelopathic compounds, but such an
      approach previously has not been applied. * The rice diterpenoid momilactones
      provide an example of natural products for which correlative biochemical evidence
      has been obtained for a role in allelopathy. Here, we apply reverse genetics,
      using knock-outs of the relevant diterpene synthases (copalyl diphosphate
      synthase 4 (OsCPS4) and kaurene synthase-like 4 (OsKSL4)), to demonstrate that
      rice momilactones are involved in allelopathy, including suppressing growth of
      the widespread rice paddy weed, barnyard grass (Echinochloa crus-galli). * Thus,
      our results not only provide novel genetic evidence for natural product-mediated
      allelopathy, but also furnish a molecular target for breeding and metabolic
      engineering of this important crop plant.

PMID- 22150233
TI  - The systemic inflammatory response after spinal cord injury in the rat is
      decreased by alpha4beta1 integrin blockade.
AB  - Abstract The systemic inflammatory response syndrome (SIRS) follows spinal cord
      injury (SCI) and causes damage to the lungs, kidney, and liver due to an influx
      of inflammatory cells from the circulation. After SCI in rats, the SIRS develops
      within 12 h and is sustained for at least 3 days. We have previously shown that
      blockade of CD11d/CD18 integrin reduces inflammation-driven secondary damage to
      the spinal cord. This treatment reduces the SIRS after SCI. In another study we
      found that blockade of alpha4beta1 integrin limited secondary cord damage more
      effectively than blockade of CD11d/CD18. Therefore we considered it important to
      assess the effects of anti-alpha4beta1 treatment on the SIRS in the lung, kidney,
      and liver after SCI. An anti-alpha4 antibody was given IV at 2 h after SCI at the
      fourth thoracic segment and the effects on the organs were evaluated at 24 h post
      injury. The migration of neutrophils into the lungs and liver was markedly
      reduced and all three organs contained fewer macrophages. In the lungs and liver,
      the activation of the oxidative enzymes myeloperoxidase (MPO), inducible nitric
      oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and gp91(phox), the production
      of free radicals, lipid peroxidation, and cell death were substantially and
      similarly reduced. Treatment effects were less robust in the kidney. Overall, the
      efficacy of the anti-alpha4beta1 treatment did not differ greatly from that of
      the anti-CD11d antibody, although details of the results differed. The SIRS after
      SCI impedes recovery, and attenuation of the SIRS with an anti-integrin treatment
      is an important, clinically-relevant finding.

PMID- 22150234
TI  - Ofatumumab demonstrates activity against rituximab-sensitive and -resistant cell
      lines, lymphoma xenografts and primary tumour cells from patients with B-cell
      lymphoma.
AB  - Ofatumumab is a new monoclonal antibody (mAb) targeting a novel membrane-proximal
      epitope on CD20. To better define ofatumumab's activity, we conducted pre
      clinical studies in rituximab-sensitive cell lines (RSCL), rituximab-resistant
      cell lines (RRCL), ofatumumab-exposed cell lines (OECLs), primary lymphoma cells,
      and a lymphoma xenograft model. RRCL and OECL were generated by repeated exposure
      of sensitive cells to escalating doses of rituximab or ofatumumab +/- human
      serum. Antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated
      cytotoxicity (CMC) assays were performed to assess cellular sensitivity to
      rituximab or ofatumumab. Ofatumumab elicited a higher rate of CMC in RSCL, RRCL
      and primary tumour cells. The chronic exposure of lymphoma cells to ofatumumab
      resulted in rituximab resistance but less ofatumumab resistance. In an in vivo
      severe combined immunodeficiency mouse model of human lymphoma, ofatumumab
      prolonged median survival compared to rituximab. While rituximab CMC diminished
      with CD20 down-regulation in RRCL passages, ofatumumab activity in vitro
      diminished to a lesser degree. Our data suggest that ofatumumab is more potent
      than rituximab in rituximab-sensitive or rituximab-resistant models and has the
      potential to decrease the development of biological resistance in patients with
      repeated exposure to anti-CD20 mAbs.

PMID- 22150235
TI  - Synoptic revision of Blabericola (Apicomplexa: Eugregarinida: Blabericolidae)
      parasitizing blaberid cockroaches (Dictyoptera: Blaberidae), with comments on
      delineating gregarine species boundaries.
AB  - Complete synoptic redescriptions, including complete morphometric data for all
      life cycle stages, species recognition characters, and differential comparisons
      are presented for the 4 gregarine species comprising Blabericola . Blabericola
      cubensis ( Peregrine, 1970 ), Blabericola haasi (Geus, 1969), Blabericola
      migrator ( Clopton, 1995 ), and Blabericola princisi ( Peregrine, 1970 ) are
      redescribed from their type hosts, i.e., the discoid cockroach Blaberus
      discoidalis , the lobster cockroach Nauphoeta cinerea , the Madagascar hissing
      cockroach Gromphadorhina portentosa , and the Bolivian cockroach Blaberus
      boliviensis , respectively. These gregarine species descriptions are stabilized
      through deposition of extensive new voucher collections. Species of Blabericola
      are distinguished by differences in relative metric ratios, morphology of
      oocysts, and by relative metric ratios of mature gamonts in association. This
      work is discussed as a model for morphological species descriptions in the
      Eugregarinorida including the 6 principles for morphological gregarine species
      descriptions, i.e., a centroid and population variation approach, adequate sample
      size, partitioning developmental variation and sexual dimorphism, recognition and
      minimization of fixation and physiological artifacts to eliminate false
      morphotypes, and comparative data sets across multiple life cycle stages.

PMID- 22150236
TI  - HIV-related stigma and NGO-isation in India: a historico-empirical analysis.
AB  - In response to World Bank critiques in 2007, the Indian Ministry of Health and
      Family Welfare declared that human immunodeficiency virus (HIV)-related stigma
      was a barrier to the participation of non-governmental organisations (NGOs) in
      the implementation of HIV prevention targeted interventions. Taking a deeper view
      of HIV-related stigma as a historically inflected process of devaluation, this
      article details the history and transformation of NGO involvement in the HIV
      epidemic from 1986 through economic liberalisation in the 1990s up to the Second
      National AIDS Control Programme (NACP II 1999-2006). It additionally examines
      findings from interviews and participant observation of NGO workers (N = 24) from
      four targeted intervention NGOs in Delhi funded under NACP II. Analysis reveals
      that a second wave of HIV-related NGO involvement has mushroomed in the past two
      decades, affording NGO workers multiple pathways to credibility in the Indian
      response to the epidemic. Contradictions embedded in the overlap of these
      pathways produce stigma, reflecting 'adverse incorporation' of the NGO workers.
      Drawing upon noteworthy exceptions to this trend from the first wave of Indian
      HIV-related NGOs, the article calls for NGO participation as an explicitly
      political project of addressing the social inequalities that shape stigma as well
      as vulnerability to illness writ large.

PMID- 22150238
TI  - Testing an integral conceptual model of frailty.
AB  - AIM: This paper is a report of a study conducted to test three hypotheses derived
      from an integral conceptual model of frailty. BACKGROUND:   The integral model of
      frailty describes the pathway from life-course determinants to frailty to adverse
      outcomes. The model assumes that life-course determinants and the three domains
      of frailty (physical, psychological, social) affect adverse outcomes, the effect
      of disease(s) on adverse outcomes is mediated by frailty, and the effect of
      frailty on adverse outcomes depends on the life-course determinants. METHODS: In
      June 2008 a questionnaire was sent to a sample of community-dwelling people, aged
      75 years and older (n = 213). Life-course determinants and frailty were assessed
      using the Tilburg frailty indicator. Adverse outcomes were measured using the
      Groningen activity restriction scale, the WHOQOL-BREF and questions regarding
      healthcare utilization. The effect of seven self-reported chronic diseases was
      examined. RESULTS: Life-course determinants, chronic disease(s), and frailty
      together explain a moderate to large part of the variance of the seven continuous
      adverse outcomes (26-57%). All these predictors together explained a significant
      part of each of the five dichotomous adverse outcomes. The effect of chronic
      disease(s) on all 12 adverse outcomes was mediated at least partly by frailty.
      The effect of frailty domains on adverse outcomes did not depend on life-course
      determinants. CONCLUSION: Our finding that the adverse outcomes are differently
      and uniquely affected by the three domains of frailty (physical, psychological,
      social), and life-course determinants and disease(s), emphasizes the importance
      of an integral conceptual model of frailty.

PMID- 22150237
TI  - RNA and epigenetic silencing: insight from fission yeast.
AB  - Post-translational modifications of histones are critical not only for local
      regulation of gene expression, but also for higher-order structure of the
      chromosome and genome organization in general. These modifications enable a
      preset state to be maintained over subsequent generations and thus provide an
      epigenetic level of regulation. Heterochromatic regions of the genome are
      epigenetically regulated to maintain a "silent state" and protein coding genes
      inserted into these regions are subject to the same epigenetic silencing. The
      fission yeast Schizosaccharomyces pombe has well characterized regions of
      heterochromatin and has proven to be a powerful model for elucidation of
      epigenetic silencing mechanisms. Research in S. pombe led to the breakthrough
      discovery that epigenetic silencing is not solely a chromatin-driven
      transcriptional repression and that RNA interference of nascent transcripts can
      guide epigenetic silencing and associated histone modifications. Over the last 10
      years, an eloquent integration of genetic and biochemical studies have greatly
      propelled our understanding of major players and effector complexes for
      regulation of RNAi-mediated epigenetic silencing in S. pombe. Here, we review
      recent research related to regulation of the epigenetic state in S. pombe
      heterochromatin, focusing specifically on the mechanisms by which transcription
      and RNA processing interact with the chromatin modification machinery to maintain
      the epigenetically silent state.

PMID- 22150239
TI  - Unilateral cervical facet dislocation: a biomechanical study of several
      constructs including unilateral lateral mass fixation supplemented by an
      interspinous cable.
AB  - OBJECT: Both ventral and dorsal operative approaches have been used to treat
      unilateral cervical facet injuries. The gold standard ventral approach is
      anterior cervical discectomy and fusion. There is, however, no clear gold
      standard dorsal operation. In this study, the authors tested the stability of
      multiple posterior constructs, including unilateral lateral mass fixation
      supplemented by an interspinous cable. METHODS: Six fresh human cervical spine
      specimens (C3-T1) were tested by applying pure moments to the C-3 vertebral body
      in increments of 0.5 Nm from 0 Nm to 2.0 Nm. Each specimen was tested in the
      following 8 conditions (in the order shown): 1) intact; 2) after destabilization
      via injury to the C5-6 facet; 3) with bilateral C5-6 lateral mass screws and
      rods; 4) after further destabilization by creating a right unilateral lateral
      mass fracture of C-5 (which rendered secure screw placement into the right C-5
      lateral mass impossible); 5) with unilateral left C5-6 lateral mass screws and
      rod; 6) with unilateral C5-6 lateral mass screws and rod supplemented with an
      interspinous cable; 7) with a bilateral multilevel dorsal construct C4-6; and 8)
      after a C5-6 anterior cervical discectomy and fusion (ACDF) procedure with a
      polyetheretherketone graft and plate. RESULTS: The bilateral C5-6 lateral mass
      construct reduced the range of C5-6 motion to 33.6% of normal. The unilateral C5
      6 lateral mass construct resulted in an increased range of motion to 110.1% of
      normal. The unilateral lateral mass construct supplemented by an interspinous
      cable reduced the C5-6 range of motion to 89.4% of normal. The bilateral C4-6
      lateral mass construct reduced the C5-6 range of motion to 44.2% of normal. The
      C5-6 ACDF construct reduced the C5-6 range of motion to 62.6% of normal.
      CONCLUSIONS: The unilateral lateral mass construct supplemented by an
      interspinous cable does reduce range of motion compared with an intact specimen,
      but is significantly inferior to a C4-6 bilateral lateral mass construct. When
      using a dorsal approach, the unilateral construct with a cable should only be
      considered in selected instances.

PMID- 22150240
TI  - Anterior cervical myelomeningocele: a rare malformation of the spinal cord.
AB  - Cervical myelomeningocele (MMC) is an uncommon congenital malformation of the
      spinal cord and accounts for a small proportion of neural tube defects. These
      lesions mostly occur in the dorsal part of the body. Only a single case of an
      anterior cervical MMC has been previously reported. The authors report a second
      case of anterior cervical MMC diagnosed when the patient began to experience
      symptoms of bilateral hand weakness in adulthood. In this patient, MR imaging of
      the cervical spine showed an anterior cervical MMC at the C6-7 level with
      hydrocephalus, thinning of the genu and trunk of the corpus callosum,
      maldevelopment of the cerebellar tonsils, and expansion of the fourth ventricle,
      posterior cranial fossa, and subarachnoid space. A CT scan and a 3D CT
      reconstruction of the cervical spine clearly demonstrated contiguous fusions of
      multiple lower-cervical vertebrae and neural arches, which was consistent with
      Type III Klippel-Feil syndrome. The patient was advised to undergo operative
      treatment to prevent the progression of her neurological deficit. However, after
      being notified of the potential neurological risks, the patient declined surgery
      and opted for conservative treatment with a hard neck collar. At 4 months' follow
      up, the patient's neurological deficit remains stable with the MMC left
      untreated. The authors presume that the possible pathogenesis of anterior
      cervical MMC may greatly differ from that of posterior lesions. This lesion could
      also be associated with multiple other spinal abnormalities, which highlights the
      importance of comprehensive preoperative radiological examinations.

PMID- 22150241
TI  - Site versus level.

PMID- 22150242
TI  - Risk perception and the economic crisis: a longitudinal study of the trajectory
      of perceived risk.
AB  - We conducted a longitudinal survey of public response to the economic crisis to
      understand the trajectory of risk perception amidst an ongoing crisis. A nation
      wide panel responded to seven surveys beginning in late September 2008 at the
      peak of the crisis and concluded in October 2009. At least 600 respondents
      participated in each survey, with 413 completing all seven surveys. Our online
      survey focused on perceptions of risk (savings, investments, retirement, job),
      negative emotions toward the financial crisis (sadness, anxiety, fear, anger,
      worry, stress), confidence in national leaders to manage the crisis (President
      Obama, Congress, Treasury Secretary, business leaders), and belief in one's
      ability to realize personal objectives despite the crisis. We employed latent
      growth curve modeling to analyze change in risk perception throughout the crisis.
      Our results suggest that, in general, people's perceptions of risk appear to
      decrease most rapidly during the initial phase of a crisis and then begin to
      level off. Negative emotion about the crisis was the most predictive of increased
      risk perception, supporting the notion of risk as feelings. Belief in one's
      ability to realize personal objectives was also predictive. Confidence in
      national leaders, however, was not predictive of perceived risk. Finally, our
      results demonstrate that groups may experience a crisis differently depending on
      a combination of personal characteristics such as gender, income, numeracy, and
      political attitude. Risk management and communication should work in sync with
      these mechanisms and differences across groups.

PMID- 22150243
TI  - Acute performance of a right ventricular automatic pacing threshold algorithm for
      implantable defibrillators.
AB  - INTRODUCTION: Automatic pacing threshold (AT) testing with threshold trending and
      output adjustment may simplify follow-up and improve cardiac rhythm device
      longevity. The objective of this study was to evaluate the performance of a new
      right ventricular (RV) AT algorithm for implantable cardioverter defibrillators
      (ICDs) using RVcoil to Can evoked response sensing. METHOD: Patients undergoing
      ICD, with or without cardiac resynchronization therapy device, implant,
      replacement, or upgrade were enrolled. A pulse generator emulator (Can) was
      temporarily placed in the device pocket. An external pacing system (Boston
      Scientific, St. Paul, MN, USA) with customized software was used for performing
      threshold tests and data acquisition. RV manual threshold and up to four AT tests
      using various pacing parameters were conducted. The threshold measurement and the
      capture detection performance of the RV AT tests were evaluated through
      comparison with visual examination of surface electrocardiogram. RESULTS: Data
      from 43 patients were analyzed. A total of 158 AT tests were performed, in which
      144 AT tests (91.1%) measured correct threshold values. No consecutive asystolic
      noncaptured beats were observed in any AT tests, and none of the AT tests
      resulted in incorrectly low threshold measurements. The difference between manual
      and AT measurements was -0.05 +/- 0.43 V. The accuracy for detecting capture and
      noncaptured beats were 95% and 99%, respectively. CONCLUSION: The RVcoil to Can
      evoked response sensing based RV AT algorithm can reliably measure pacing
      threshold for ICDs, including CRT-Ds.

PMID- 22150244
TI  - Periosteal muscle anchoring for large angle incomitant squint.
AB  - PURPOSE: To describe a surgical technique for correcting very large angle
      exodeviations and determine long term outcomes leading to the evolution of
      surgical technique. METHODS: A consecutive series of seven patients with large
      angle, incomitant squint were operated on at Moorfields Eye Hospital over a five
      year period using periosteal anchoring by a joint Strabismus/Adnexal team. All
      patients underwent anchoring of the insertion of the medial rectus (MR) muscle to
      the periosteum of the medial orbital wall via a retrocaruncular approach, with or
      without lateral rectus (LR) disinsertion and suturing to the lateral orbital rim
      connective tissue. Retrospective analysis of notes assessed previous procedures,
      prism dioptre (PD) deviations and complications. RESULTS: Included were seven
      eyes (five right, two left) of seven patients (two female, five male). Median age
      at first anchoring procedure was 25 years (range 4-57). Mean follow up was 34
      months (range 8-66). Six patients had long-standing third nerve palsy, one
      patient had Moebius syndrome. Pre-operative exotropia ranged from 45 to 115 PDs
      (mean 76, median 75). At the final follow up, all patients had reduced horizontal
      deviations ranging from 0 to 80 PDs (mean 34, median 30). Further surgery was
      required in three patients all of whom did not undergo release of the LR muscle
      at the first procedure. CONCLUSION: Large angle incomitant divergent squints
      present a particularly difficult surgical challenge. We advocate a combined bi
      rectus fixation approach to hold the globe in the primary position.

PMID- 22150245
TI  - Cued recall and other cognitive tasks to facilitate dementia recognition in
      primary care.
AB  - OBJECTIVES: To compare the accuracy of commonly used tasks with that of the
      Visual Association Test (VAT), a conceptually different test involving cued
      recall of pictorial stimuli, in the recognition of dementia within primary care.
      DESIGN: A cross-sectional diagnostic study of concurrent validity. SETTING:
      Twenty-nine German primary care practices. PARTICIPANTS: Four hundred twenty
      three individuals in primary care participating in a longitudinal cohort study.
      MEASUREMENTS: Participants underwent a comprehensive neuropsychological
      interview. The validated clinical dementia diagnosis was used as reference
      standard. Index tests comprised the VAT, Mini-Cog, clock drawing, verbal fluency,
      episodic memory, and subjective complaints. Validity parameters were calculated;
      possible confounders of test performance (age, sex, education, comorbidity,
      depression, language) were evaluated. RESULTS: Twenty-one participants (5%) had
      dementia according to the reference standard. The VAT distinguished dementia from
      nondementia with a sensitivity of 95.2% (95% confidence interval (CI) = 86.1
      100.0), a specificity of 96.0% (95% CI = 94.1-97.9), a positive predictive value
      (PPV) of 55.6% (95% CI = 39.3-71.8), and a negative predictive value (NPV) of
      99.7% (95% CI = 99.2-100.0). The next-most-accurate tasks were the Mini-Cog and
      immediate and delayed recall. Their sensitivity and NPV are similar to those of
      the VAT, but their PPV and specificity were significantly lower than those of the
      VAT. Age and depression affected all test scores. CONCLUSION: The VAT (cued
      recall of pictorial material) is superior to other tasks for the recognition of
      dementia in terms of higher specificity and PPV. Age-specific cutoff scores may
      improve the validity of all tests.

PMID- 22150246
TI  - Application of artificial neural networks for feature recognition in image
      registration.
AB  - Image registration is a process of aligning two or more images taken at different
      times or using different sensors by transforming the same area into one
      coordinate system. Imaging conditions, image and area deteriorations from
      repeated sectioning, are serious impediments to successful image registration.
      The application of artificial neural networks for feature recognition is
      introduced to the field of metallurgy to assist in an automated approach to image
      registration of metallurgical microstructures. Low susceptibility to feature
      deterioration, often occurring during serial sectioning, is demonstrated and
      assessed. The process of image registration using an artificial neural network to
      aid in feature segmentation is performed using computer generated shapes and a
      metallurgical microstructure.

PMID- 22150248
TI  - Let's (not) do it again: secondary prevention of cardiovascular disease in women.

PMID- 22150247
TI  - Conservation of Dcm-mediated cytosine DNA methylation in Escherichia coli.
AB  - In Escherichia coli, cytosine DNA methylation is catalyzed by the DNA cytosine
      methyltransferase (Dcm) protein and occurs at the second cytosine in the sequence
      5'CCWGG3'. Although the presence of cytosine DNA methylation was reported over 35
      years ago, the biological role of 5-methylcytosine in E. coli remains unclear. To
      gain insight into the role of cytosine DNA methylation in E. coli, we (1)
      screened the 72 strains of the ECOR collection and 90 recently isolated
      environmental samples for the presence of the full-length dcm gene using the
      polymerase chain reaction; (2) examined the same strains for the presence of 5
      methylcytosine at 5'CCWGG3' sites using a restriction enzyme isoschizomer
      digestion assay; and (3) quantified the levels of 5-methyl-2'-deoxycytidine in
      selected strains using liquid chromatography tandem mass spectrometry. Dcm
      mediated cytosine DNA methylation is conserved in all 162 strains examined, and
      the level of 5-methylcytosine ranges from 0.86% to 1.30% of the cytosines. We
      also demonstrate that Dcm reduces the expression of ribosomal protein genes
      during stationary phase, and this may explain the highly conserved nature of this
      DNA modification pathway.

PMID- 22150249
TI  - Birth cohort changes in Chinese adolescents' mental health.
AB  - In China, rapid economic growth and increasing social problems constitute two
      basic characteristics of contemporary social change. During the process of
      dramatic social change, an emerging question is how adolescents' mental health
      has changed across birth cohorts. The present paper reviews four studies of
      crosstemporal meta-analysis conducted by us. By meta-analysis of previous
      literature, we examined changes in mean scores on mental health measures over
      time (from the early 1990s to the mid-2000s). It was found that since the early
      1990s, Chinese adolescents' mental health deteriorated across birth cohorts,
      shown in increased scores on the negative indicators of mental health (e.g.
      mental problems, anxiety, and depression), whereas self-esteem as a positive
      trait decreased. The dropping trend in Chinese adolescents' mental health could
      be attributed to social change, especially increasing social problems. Therefore,
      adequate attention must be paid to potential influences of social change on
      individuals' psychological development.

PMID- 22150250
TI  - The usefulness of the Simplified Erosion Narrowing Score (SENS) in clinical
      practice for estimating joint damage in early rheumatoid arthritis.

PMID- 22150251
TI  - Complexities in hindcasting models--when should we say enough is enough.

PMID- 22150252
TI  - "Cauliflower ear" in a teenager: a possible sign of child abuse.
AB  - "Cauliflower ear" is a perichondritis of the auricular pavilion, usually caused
      by infection or repeated trauma. In children, this entity is considered
      infrequent. We present the case of a 10-year-old girl living in a child care
      institution with "cauliflower ear" that was interpreted as a possible sign of
      child abuse.

PMID- 22150254
TI  - You may need the vagus nerve to understand pathophysiology and to treat diseases.
AB  - Can different pathophysiological mechanisms and risk factors leading to various
      diseases be linked with altered transmission of signals by one common pathway?
      The present article provides evidence for the hypothesis that adequate vagal
      nerve activity reduces the risk of major diseases, via common basic mechanisms
      and interim risk factors. These diseases include cardiovascular disease, cancer,
      Alzheimer's disease and the metabolic syndrome. Three basic mechanisms contribute
      to such illnesses: local oxidative stress and DNA damage, inflammatory reactions
      and excessive sympathetic responses, all of which are inhibited by vagal nerve
      activity. Efferent vagal activity that can be non-invasively measured by HRV
      (heart rate variability), derived from an ECG, is inversely related to all three
      basic mechanisms, to various risk factors (e.g. diabetes and dyslipidaemia) and,
      more broadly, to the diseases as well. Finally, vagal activity is proposed to
      moderate the effects of risk factors on developing such illnesses. By proposing
      an integrative neurobiological model of major diseases, identifying people at
      risk for, and treating patients with, such diseases may be done more efficiently.
      People with low HRV may be identified and subsequently treated by vagus nerve
      activation to possibly prevent or treat such illnesses. This proposed disease
      paradigm may have important preventative and therapeutic implications, whose
      clinical effects need to be investigated.

PMID- 22150262
TI  - Multidisciplinary research on tuberculosis. Editorial.

PMID- 22150253
TI  - Impact of exercise training on arterial wall thickness in humans.
AB  - Thickening of the carotid artery wall has been adopted as a surrogate marker of
      pre-clinical atherosclerosis, which is strongly related to increased
      cardiovascular risk. The cardioprotective effects of exercise training, including
      direct effects on vascular function and lumen dimension, have been consistently
      reported in asymptomatic subjects and those with cardiovascular risk factors and
      diseases. In the present review, we summarize evidence pertaining to the impact
      of exercise and physical activity on arterial wall remodelling of the carotid
      artery and peripheral arteries in the upper and lower limbs. We consider the
      potential role of exercise intensity, duration and modality in the context of
      putative mechanisms involved in wall remodelling, including haemodynamic forces.
      Finally, we discuss the impact of exercise training in terms of primary
      prevention of wall thickening in healthy subjects and remodelling of arteries in
      subjects with existing cardiovascular disease and risk factors.

PMID- 22150263
TI  - Understanding the gender aspects of tuberculosis: a narrative analysis of the
      lived experiences of women with TB in slums of Delhi, India.
AB  - There have been few ethnographic studies on gender aspects of tuberculosis (TB).
      In this article, drawing on a qualitative study on TB in Delhi slums and through
      an intersectional analysis of group interviews and personal narratives of women
      living with TB, I bring forth the "genderization" of TB and the associated
      sufferings for women. With my findings I demonstrate how gender, in conjunction
      with other social forces, influences the disease outcomes and stigmatizes women,
      how lives in slums are uniquely organized by multiple discourses that contribute
      to the gender makings of TB, and, finally, how women strategize to reduce their
      burden of illness.

PMID- 22150264
TI  - A woman's lived experience with directly observed therapy for tuberculosis-a case
      study.
AB  - This is a case study to investigate the lived experience of tuberculosis (TB)
      treatment for a Hispanic female. The theme was accumulating aggravation. Her
      daily life was interrupted with appointments and negative side effects. She had
      to wear a mask that made her feel isolated. She felt ignored by her doctors.
      Although she experienced the opposite feeling of being overly observed, the
      informant began to feel like she was always being watched. The participant
      described herself as paranoid due to the threat of imprisonment for nonadherence.
      The accumulating aggravation made the directly observed therapy short-course
      (DOTS) experience a difficulty and stressful experience.

PMID- 22150265
TI  - Filipino women's tuberculosis care seeking experience in an urban poor setting: a
      socioecological perspective.
AB  - Urban, poor Filipino women tend to delay seeking care for tuberculosis (TB),
      which increases their risk for morbidity and mortality. We interviewed 13 women
      and conducted three focus group discussions to characterize their TB care seeking
      pathways and identify the barriers and facilitators that influence care seeking
      at multiple levels. The quality of health services, shame associated with TB,
      financial insecurity, and familial responsibilities hindered care seeking, while
      support from community health volunteers and family members encouraged it.
      Strategies to improve TB control should create social support systems and improve
      the quality of health services to promote timely care seeking.

PMID- 22150266
TI  - Health beliefs and practices related to cancer screening among Arab Muslim women
      in an urban community.
AB  - In this exploratory study I investigated the participation status in breast and
      cervical cancer screening of a group of American immigrant Arab Muslim women
      (AMW). Perceived knowledge of and barriers to screening participation,
      relationships among demographic variables, health practice and beliefs, and self
      reports of traditionalism and acculturation also are studied. Factors including
      religious and cultural beliefs, economic concerns, and modesty and embarrassment
      were considered. To reach the goals of Healthy People 2010 (HP 2010), an
      effective and meaningful educational initiative to raise awareness about breast
      and cervical cancer of AMW will require specific interventions consistent with
      their cultural and religious traditions.

PMID- 22150267
TI  - Does culture matter?: a cross-national investigation of women's responses to
      cancer prevention campaigns.
AB  - We examined how culture influences the persuasive effects of health campaigns
      that promote early screening for cancers that occur in women. Two message
      dimensions were included: individualistic vs. collectivistic appeal and gain vs.
      loss frame. A total of 955 females from three countries-the United States, South
      Korea, and Japan-participated in the experiment. From the results, we found that
      message framing alone did not significantly influence the effectiveness of public
      campaigns for women's cancer prevention; and this tendency was similar across the
      three countries. Gain-framed messages are likely to be more persuasive when
      combined with a collectivistic appeal, however, whereas loss-framed messages tend
      to be more effective when combined with an individualistic appeal in both the
      United States and South Korea; but this result was not the case for Japan. Based
      on the findings, we suggested theoretical and managerial implications as well as
      several directions for future research.

PMID- 22150268
TI  - The formation of early stage adipocere in submerged remains: a preliminary
      experimental study.
AB  - In some circumstances, the presence of adipocere may retard decomposition and
      complicate postmortem interval estimation. This article explores the correlation
      between Accumulated Degree Days (ADD) and early stage formation of adipocere.
      Sixty wild rabbit (Oryctolagus cuniculus) carcasses were used in this experiment;
      a control group (N = 30) deposited directly on the ground surface and an
      experimental group (N = 30) completely submersed in water in individual buckets.
      Data (water and inner body temperature, pH, and total body score) were collected
      every 100 ADD. Results indicated that early stage adipocere is correlated to ADD
      and that its formation on submersed remains is more likely to occur after 630
      ADD. Skin sloughing promoted the formation of adipocere. No adipocere was formed
      on any of the control group rabbits. This study also highlights the fact that
      multiple factors influence adipocere formation and it is suggested that further
      research needs to be conducted into this area.

PMID- 22150269
TI  - Persistence of bacterial proteolytic enzymes in lake ecosystems.
AB  - This study analyzes proteolytic enzyme persistence and the role of dead (or
      metabolically inactive) aquatic bacteria in organic matter cycling. Samples from
      four lakes of different trophic status were used. Irrespective of the trophic
      status of the examined lakes, bacterial aminopeptidases remained active even 72 h
      after the death of the bacteria that produced them. The total pool of proteolytic
      enzymes in natural lake water samples was also stable. We found that the rates of
      amino acid enzymatic release from proteinaceous matter added to preserved lake
      water sample were constant for at least 96 h (r(2)  = 0.99, n = 17, P <= 0.0001,
      V(max)  = 84.6 nM h(-1) ). We also observed that proteases built into bacterial
      cell debris fragments remained active for a long time, even after the total
      destruction of cells. Moreover, during 24 h of incubation time, about 20% of
      these enzymatically active fragments adsorbed onto natural seston particles,
      becoming a part of the 'attached enzymes system' that is regarded as the 'hot
      spot' of protein degradation in aquatic ecosystems.

PMID- 22150270
TI  - Semen variation in a population of fertile donors: evaluation in a French centre
      over a 34-year period.
AB  - Although it has been suspected that there is a decrease in semen quality over
      time, the results reported to date remain debatable because of methodological
      issues. The aim of the study reported here was to investigate the evolution of
      semen quality over time in a population of 1114 fertile candidates for sperm
      donation at CECOS, Tours, between 1976 and 2009. We investigated semen volume,
      sperm concentration, progressive motility, vitality, percentage of normal forms
      and multiple abnormalities index of the first ejaculate in this population. We
      did not find a decline in semen volume, whereas we observed a significant
      decrease in total sperm count (from 443.2 million in 1976 to 300.2 million in
      2009), motility (from 64% in 1976 to 49% in 2009) and vitality (from 88% to 80%).
      Moreover, a significant decline in the percentage of normal forms was noted
      between 1976 and 1997 (from 67% to 26%) with a steady rise in the multiple
      abnormalities index between 1998 and 2009 (from 1.19 to 1.65). This study
      involving a population of fertile men from a restricted area revealed various
      degrees of decline in semen parameters over a period of 34 years. These findings
      will have to be compared with findings in other geographical areas.

PMID- 22150271
TI  - The chromatin-binding protein HMGN3 stimulates histone acetylation and
      transcription across the Glyt1 gene.
AB  - HMGNs are nucleosome-binding proteins that alter the pattern of histone
      modifications and modulate the binding of linker histones to chromatin. The HMGN3
      family member exists as two splice forms, HMGN3a which is full-length and HMGN3b
      which lacks the C-terminal RD (regulatory domain). In the present study, we have
      used the Glyt1 (glycine transporter 1) gene as a model system to investigate
      where HMGN proteins are bound across the locus in vivo, and to study how the two
      HMGN3 splice variants affect histone modifications and gene expression. We
      demonstrate that HMGN1, HMGN2, HMGN3a and HMGN3b are bound across the Glyt1 gene
      locus and surrounding regions, and are not enriched more highly at the promoter
      or putative enhancer. We conclude that the peaks of H3K4me3 (trimethylated Lys(4)
      of histone H3) and H3K9ac (acetylated Lys(9) of histone H3) at the active Glyt1a
      promoter do not play a major role in recruiting HMGN proteins. HMGN3a/b binding
      leads to increased H3K14 (Lys(14) of histone H3) acetylation and stimulates
      Glyt1a expression, but does not alter the levels of H3K4me3 or H3K9ac enrichment.
      Acetylation assays show that HMGN3a stimulates the ability of PCAF [p300/CREB
      (cAMP-response-element-binding protein)-binding protein-associated factor] to
      acetylate nucleosomal H3 in vitro, whereas HMGN3b does not. We propose a model
      where HMGN3a/b-stimulated H3K14 acetylation across the bodies of large genes such
      as Glyt1 can lead to more efficient transcription elongation and increased mRNA
      production.

PMID- 22150273
TI  - Mechanisms of autophagy and pexophagy in yeasts.
AB  - Autophagy is a process of recycling of the intracellular constituents using
      vacuoles (lysosomes). General autophagy occurs due to involvement of highly
      conservative components found in all eukaryotes, from yeasts to higher plants and
      humans. Autophagy also could be a selective process and be involved in regulation
      of the cellular number of organelles, including that of peroxisomes. The process
      of specific autophagic peroxisome degradation is known as pexophagy. Yeasts
      appear to be convenient model for studying molecular mechanisms of pexophagy, and
      most known ATG genes (from the term AuTophaGy) were identified in yeast studies.
      This review examines characteristics of general autophagy, other types of
      autophagy as well as pexophagy, in particular, functions of Atg proteins in
      general autophagy and in macro- and micropexophagy. Special attention is given to
      mechanisms of phagophore assembly, the role of phosphatidylinositol-3-phosphate
      in pexophagy, the role of peroxines (proteins involved in peroxisome biogenesis)
      in pexophagy, as well as properties of Atg proteins specifically involved in
      micropexophagy.

PMID- 22150272
TI  - Antimicrobial photodynamic therapy as a strategy to arrest enamel
      demineralization: a short-term study on incipient caries in a rat model.
AB  - In this study we developed a rat model of incipient caries to investigate the
      short-term effects of antimicrobial photodynamic therapy (aPDT) on oral
      microbiota regulation and demineralization arrestment. Twenty-nine male rats were
      submitted to caries induction. Early carious lesion was confirmed by optical
      coherence tomography (OCT) 5 days after experiment beginning in five animals. The
      remaining animals (n = 24) were randomly divided into two groups: control (n =
      12), animals were untreated; and aPDT (n = 12), animals were treated with 100 MUM
      of methylene blue for 5 min and irradiated by a light emitting diode at lambda =
      645 +/- 30 nm, fluence rate of 480 mW cm(-2) and exposure time of 3 min.
      Bacterial burden was evaluated before, immediately after, 3, 7 and 10 days
      following treatment, and total number of microaerophilic bacteria was counted.
      OCT was also used to quantify teeth demineralization. A significant bacterial
      decrease of about 1.6 log was observed immediately after aPDT. Besides, bacterial
      load in aPDT group remained lower than control until 10 days post-treatment (P <
      0.05) and variation of optical attenuation coefficient before and after aPDT was
      15%, corroborating to caries arrestment. Put together, these findings suggest
      that aPDT was competent to reduce cariogenic bacteria and to avoid further
      mineral loss.

PMID- 22150274
TI  - Lipids in mammalian hibernation and artificial hypobiosis.
AB  - Membrane lipids-phospholipids, fatty acids, and cholesterol-participate in
      thermal adaptation of ectotherms (bacteria, amphibians, reptiles, fishes) mainly
      via changes in membrane viscosity caused by the degree of fatty acids
      unsaturation, cholesterol/phospholipids ratio, and phospholipid composition.
      Studies of thermal adaptation of endotherms (mammals and birds) revealed the
      regulatory role of lipids in hibernation. Cholesterol and fatty acids participate
      in regulation of the parameters of torpor, gene expression, and activity of
      enzymes of lipid metabolism. Some changes in lipid metabolism during artificial
      and natural hypobiosis, namely, increased concentration of cholesterol and fatty
      acids in blood and decreased cholesterol concentration in neocortex, are
      analogous to those observed under stress conditions and coincide with mammalian
      nonspecific reactions to environmental agents. It is shown that the effects of
      artificial and natural hypobiosis on lipid composition of mammalian cell
      membranes are different. Changes in lipid composition cause changes in membrane
      morphology during mammalian hibernation. The effect of hypobiosis on lipid
      composition of membranes and cell organelles is specific and seems to be defined
      by the role of lipids in signaling systems. Comparative study of lipid metabolism
      in membranes and organelles during natural and artificial hypobiosis is promising
      for elucidation of adaptation of mammals to low ambient temperatures.

PMID- 22150275
TI  - Diversity of integrase-hydrolyzing IgGs and IgMs from sera of HIV-infected
      patients.
AB  - It was previously shown that small fractions of IgGs and IgMs from the sera of
      AIDS patients specifically hydrolyze only HIV integrase (IN) but not many other
      tested proteins. Here we present evidence showing that these IgGs and IgMs are
      extreme catalytically heterogeneous. Affinity chromatography on IN-Sepharose
      using elution of IgGs (or IgMs) with different concentration of NaCl and acidic
      buffer separated catalytic antibodies (ABs) into many AB subfractions
      demonstrating different values of K(m) for IN and k(cat). Nonfractionated IgGs
      and IgMs possess serine-, thiol-, acidic-like, and metal-dependent proteolytic
      activity. Metal-dependent activity of abzymes increases in the presence of ions
      of different metals. In contrast to canonical proteases having one pH optimum,
      initial nonfractionated IgGs and IgMs demonstrate several optima at pH from 3 to
      10. The data obtained show that IN-hydrolyzing polyclonal IgG and IgM of HIV
      infected patients are cocktails of anti-IN ABs with different structure of the
      active centers possessing various affinity to IN, pH optima, and relative rates
      of the specific substrate hydrolysis.

PMID- 22150276
TI  - Changes in isoform composition, structure, and functional properties of titin
      from Mongolian gerbil (Meriones unguiculatus) cardiac muscle after space flight.
AB  - Changes in isoform composition, secondary structure, and titin phosphorylation in
      Mongolian gerbil (Meriones unguiculatus) cardiac muscle were studied after 12-day
      long space flight onboard the Russian spacecraft Foton-M3. The effect of titin on
      the actin-activated myosin ATPase activity at pCa 7.5 and 4.6 was also studied.
      Almost twofold increase in titin long N2BA isoform content relative to that of
      short N2B isoform was found on electrophoregrams of cardiac muscle left ventricle
      of the flight group gerbils. Differences in secondary structure of titin isolated
      from cardiac muscle of control and flight groups of gerbils were found. An
      increase in phosphorylation (1.30-1.35-fold) of titin of cardiac muscle of the
      flight group gerbils was found. A decrease in activating effect of titin of
      cardiac muscle of the flight group gerbils on actomyosin ATPase activity in vitro
      was also found. The observed changes are discussed in the context of M.
      unguiculatus cardiac muscle adaptation to conditions of weightlessness.

PMID- 22150277
TI  - Influence of intramolecular interactions on conformational and dynamic properties
      of analogs of heptapeptide AFP(14-20).
AB  - Conformational and dynamic properties of proteins and peptides play an important
      role in their functioning. However, mechanisms that underlie this influence have
      not been fully elucidated. In the present work we computationally constructed
      analogs of heptapeptide AFP(14-20) (LDSYQCT) - one of the biologically active
      sites of human alpha-fetoprotein (AFP) - to study their conformational and
      dynamic properties using molecular dynamics simulation. Analogs were obtained by
      point substitutions of amino acid residues taking into account differences in
      their physicochemical properties and also on the basis of analysis of amino acid
      substitutions in the AFP(14-20)-like motifs revealed in different physiologically
      active proteins. It is shown that changes in conformational mobility of amino
      acid residues of analogs are due to disruption or arising of intramolecular
      interactions that, in turn, determine existence of steric restrictions during
      rotation around covalent bonds of the peptide backbone. Substitution of an amino
      acid by another one with significant difference in physicochemical properties may
      not lead to remarkable changes in conformational and dynamic properties of the
      peptide if intramolecular interactions remain unchanged.

PMID- 22150278
TI  - Interaction of synthetic peptide octarphin with rat myocardium membranes.
AB  - A selective agonist of non-opioid beta-endorphin receptor synthetic peptide
      octarphin (TPLVTLFK, specific activity 28 Ci/mmol) was prepared. The
      [3H]octarphin binding to rat myocardium membranes before and after experimental
      myocardial infarction (EMI) was studied. It was found that [3H]octarphin with
      high affinity and specificity binds to non-opioid beta-endorphin receptor of rat
      myocardium membranes before EMI: K(d1) value of the [3H]octarphin specific
      binding to membranes was 1.8 +/- 0.2 nM. In 3 h after EMI a sharp lowering in
      affinity of the binding is observed (K(d2) = 13.3 +/- 0.4 nM), and in 48 h its
      almost complete restoration (K(d4) = 2.2 +/- 0.3 nM). The results indicate
      participation of non-opioid beta-endorphin receptor in the regulation of
      myocardial activity.

PMID- 22150279
TI  - Acetylation degree of chitin in the protective response of wheat plants.
AB  - Influences on the acetylation degree of chitin manifested by proteins from
      cultural filtrates of strains of the fungus Septoria nodorum different in
      aggressiveness and of extracts from leaves of the susceptible (Triticum aestivum)
      and resistant (Triticum timopheevii) wheat plants infected with these strains
      were studied. Chitin deacetylase was found among the extracellular proteins of
      the fungus. Its activity was higher in the aggressive strain of the fungus than
      in the non-aggressive one, and this suggested that this enzyme could play an
      important role in the further formation of compatible relationship of the
      pathogens with the plants. Protein extracts from the susceptible wheat seedlings
      infected with the septoriosis agent also contained a component decreasing the
      acetylation degree of chitin. Protein extracts from the resistant wheat seedlings
      increased the chitin acetylation degree. It is supposed that this can be a
      pattern of the plant counteracting the action of chitin deacetylases of the
      pathogen.

PMID- 22150280
TI  - Classification and characterization of putative cytochrome P450 genes from Panax
      ginseng C. A. Meyer.
AB  - In plants heme containing cytochrome P450 (P450) is a superfamily of
      monooxygenases that catalyze the addition of one oxygen atom from O2 into a
      substrate, with a substantial reduction of the other atom to water. The function
      of P450 families is attributed to chemical defense mechanism under terrestrial
      environmental conditions; several are involved in secondary and hormone
      metabolism. However, the evolutionary relationships of P450 genes in Panax
      ginseng remain largely unknown. In the present study, data mining methods were
      implemented and 116 novel putative P450 genes were identified from Expressed
      Sequence Tags (ESTs) of a ginseng database. These genes were classified into four
      clans and 22 families by sequence similarity conducted at amino acid level. The
      representative putative P450 sequences of P. ginseng and known P450 family from
      other plants were used to construct a phylogenetic tree. By comparing with other
      genomes, we found that most of the P450 genes from P. ginseng can be found in
      other dicot species. Depending on P450 family functions, seven P450 genes were
      selected, and for that organ specific expression, abiotic, and biotic studies
      were performed by quantitative reverse transcriptase-polymerase chain reaction.
      Different genes were found to be expressed differently in different organs.
      Biotic stress and abiotic stress transcript level was regulated diversely, and
      upregulation of P450 genes indicated the involvement of certain genes under
      stress conditions. The upregulation of the P450 genes under methyl jasmonate and
      fungal stress justifies the involvement of specific genes in secondary metabolite
      biosynthesis. Our results provide a foundation for further elucidating the actual
      function and role of P450 involved in various biochemical pathways in P. ginseng.

PMID- 22150281
TI  - Investigation of the redox interaction between Mn-bicarbonate complexes and
      reaction centers from Rhodobacter sphaeroides R-26, Chromatium minutissimum, and
      Chloroflexus aurantiacus.
AB  - The change in the dark reduction rate of photooxidized reaction centers (RC) of
      type II from three anoxygenic bacteria (Rhodobacter sphaeroides R-26, Chromatium
      minutissimum, and Chloroflexus aurantiacus) having different redox potentials of
      the P(+)/P pair and availability of RC for exogenous electron donors was
      investigated upon the addition of Mn(2+) and HCO(3)(-). It was found that the
      dark reduction of P(870)(+) from Rb. sphaeroides R-26 is considerably accelerated
      upon the combined addition of 0.5 mM MnCl(2) and 30-75 mM NaHCO(3) (as a result
      of formation of "low-potential" complexes [Mn(HCO(3))(2)]), while MnCl(2) and
      NaHCO(3) added separately had no such effect. The effect is not observed either
      in RC from Cf. aurantiacus (probably due to the low oxidation potential of the
      primary electron donor, P(865), which results in thermodynamic difficulties of
      the redox interaction between P(865)(+) and Mn(2+)) or in RC from Ch.
      minutissimum (apparently due to the presence of the RC-bound cytochrome
      preventing the direct interaction between P(870)(+) and Mn(2+)). The absence of
      acceleration of the dark reduction of P(870)(+) in the RC of Rb. sphaeroides R-26
      when Mn(2+) and HCO(3)(-) were replaced by Mg(2+) or Ca(2+) and by formate,
      oxalate, or acetate, respectively, reveals the specificity of the Mn2+
      bicarbonate complexes for the redox interaction with P(+). The results of this
      work might be considered as experimental evidence for the hypothesis of the
      participation of Mn(2+) complexes in the evolutionary origin of the inorganic
      core of the water oxidizing complex of photosystem II.

PMID- 22150282
TI  - In vivo injected mitochondria-targeted plastoquinone antioxidant SkQR1 prevents
      beta-amyloid-induced decay of long-term potentiation in rat hippocampal slices.
AB  - Addition of 200 nM beta-amyloid 1-42 (Abeta) to a rat hippocampal slice impairs
      the induction of a long-term post-tetanic potentiation (LTP) of population spike
      (PS) in pyramidal neurons of the CA1 field of hippocampus. Intraperitoneal
      injection into the rat of the mitochondria-targeted plastoquinone derivative
      SkQR1 (1 umol/kg of weight given 24 h before the slices were made) abolishes the
      deleterious effect of Abeta on LTP. These data demonstrate that SkQR1 therapy is
      able to compensate the Abeta-induced impairments of long-term synaptic plasticity
      in the hippocampus, which are the main cause of loss of memory and other
      cognitive functions associated with Alzheimer's disease.

PMID- 22150284
TI  - Evaluation of a flow cytometry-based assay for natural killer cell activity in
      clinical settings.
AB  - Natural killer (NK) cells are not only important in first line defence against
      viral and bacterial infections, but also in immune surveillance of malignant
      cells and thus NK cell cytotoxicity is primary indicator of immune function.
      Although chromium release assay is recognized as 'gold standard' for measuring NK
      cell activity, it has disadvantages like use of radioactive compounds, poor
      loading and high spontaneous release. It is difficult to perform this assay in
      clinical laboratory because of difficulties with disposal of radioactive waste
      and standardization problems. We describe a flow cytometry-based assay for the
      measurement of NK cell activity by incorporating fluorescent dye, DiO, into
      membranes of target cells. NK cell activity was measured at baseline, 1 and 4
      weeks follow-up in 20 normal healthy individuals on a dietary supplement
      immunomodulator to enhance NK cell function. Mean baseline NK cell activity
      percentage (21.5; SD = 9.3) increased significantly to a maximum level at 1 week
      (31.3%; SD = 7.9; P = 0.007) and then returned to baseline level at 4 weeks
      (21.5; SD = 8.3). An important feature of flow cytometry-based assays is its
      ability to discriminate effector cells from target cells, and potential for
      explaining molecular interactions underlying target cell lysis. Under clinical
      settings, this assay will be of interest for frequently monitoring immunological
      status of patients on treatment for various diseases that affect their immune
      status. The assay is easy to perform without using radioactive material and thus
      could become a tool for monitoring pathogenesis and immune reconstitution.

PMID- 22150285
TI  - Lactation deficit in OFA hr/hr rats may be caused by differential sensitivity to
      stress compared with Wistar and Sprague Dawley rats.
AB  - OFA hr/hr (OFA) rats present a major lactation deficit that impairs offspring
      survival. To explore whether abnormal stress responsiveness causes this deficit,
      we compared their hormonal (prolactin, progesterone, and corticosterone)
      responses to stress (room change and 2-min ether exposure) with those of Wistar
      and Sprague Dawley (SD) rats. We tested responses during the estrous cycle,
      pregnancy, lactation, after ovariectomy, and ovarian steroid hormone priming, and
      responses to suckling. We evaluated hypothalamic expression of receptors for
      prolactin (PRLRlong) and the isoforms of receptors for progesterone (PRA and B)
      and estrogen (ERalpha and beta) in late pregnancy. We tested whether
      administration of an anxiolytic (diazepam) improved lactation. Ether exposure
      increased circulating levels of the three hormones in the three strains of rats,
      cycling and ovariectomized, but was less effective in pregnancy and lactation.
      Elevated estrogen level (estrus and estradiol-treated ovariectomized rats)
      potentiated the prolactin response more in SD and OFA rats than in Wistar rats.
      Elevated progesterone level (late pregnancy, lactation, progesterone-treated
      ovariectomized rats) inhibited the prolactin response less in OFA than in SD or
      Wistar rats. Ether exposure inhibited the prolactin and oxytocin responses to
      suckling only in OFA rats. Diazepam treatment increased pup survival rate and the
      prolactin response to suckling. Hypothalamic total PR mRNA content, assayed by RT
      PCR, was higher in pregnant OFA rats compared with SD and Wistar rats, but the
      PRB/PRA protein ratio determined by Western blot was lowest in Wistar rats,
      intermediate in OFA rats, and highest in SD rats. The heightened sensitivity to
      stress of lactating OFA rats may contribute to their lactational deficit and be
      caused by a combination of hypoprolactinemia and reduced inhibitory capacity of
      progesterone.

PMID- 22150287
TI  - New species of Falcaustra (Nematoda: Kathlaniidae) in Platysternon megacephalum
      (Testudines: Platysternidae) from China.
AB  - Falcaustra taimoshanensis n. sp. (Ascaridida, Kathlaniidae) from the feces of
      Platysternon megacephalum (Testudines; Platysternidae) is described and
      illustrated. Falcaustra taimoshanensis n. sp. represents the 32nd Oriental
      species assigned to the genus and is distinguished from other species by the
      distribution pattern of the caudal papillae (6 precloacal, 2 adcloacal, 12
      postcloacal, and 1 median), length of spicules (765-791 um), and presence of 1
      pseudosucker.

PMID- 22150286
TI  - Inhibition of heart formation by lithium is an indirect result of the disruption
      of tissue organization within the embryo.
AB  - Lithium is a commonly used drug for the treatment of bipolar disorder. At high
      doses, lithium becomes teratogenic, which is a property that has allowed this
      agent to serve as a useful tool for dissecting molecular pathways that regulate
      embryogenesis. This study was designed to examine the impact of lithium on heart
      formation in the developing frog for insights into the molecular regulation of
      cardiac specification. Embryos were exposed to lithium at the beginning of
      gastrulation, which produced severe malformations of the anterior end of the
      embryo. Although previous reports characterized this deformity as a posteriorized
      phenotype, histological analysis revealed that the defects were more
      comprehensive, with disfigurement and disorganization of all interior tissues
      along the anterior-posterior axis. Emerging tissues were poorly segregated and
      cavity formation was decreased within the embryo. Lithium exposure also
      completely ablated formation of the heart and prevented myocardial cell
      differentiation. Despite the complete absence of cardiac tissue in lithium
      treated embryos, exposure to lithium did not prevent myocardial differentiation
      of precardiac dorsal marginal zone explants. Moreover, precardiac tissue freed
      from the embryo subsequent to lithium treatment at gastrulation gave rise to
      cardiac tissue, as demonstrated by upregulation of cardiac gene expression,
      display of sarcomeric proteins, and formation of a contractile phenotype.
      Together these data indicate that lithium's effect on the developing heart was
      not due to direct regulation of cardiac differentiation, but an indirect
      consequence of disrupted tissue organization within the embryo.

PMID- 22150288
TI  - Relationship of the body mass index and childhood psoriasis in a Chinese Han
      population: a hospital-based study.

PMID- 22150289
TI  - De novo polycythaemia vera arising 5 years following acute myeloid leukemia
      remission: suggestion of a chemotherapy resistant JAK2 clone.

PMID- 22150290
TI  - Staff and patient views of the concept of hope on a stroke unit: a qualitative
      study.
AB  - AIM: This study explores the experience of hope for patients and staff in the
      context of a British stroke unit. BACKGROUND: Hope is identified as a useful
      concept for exploring how people find meaning in recovery from illness.
      Uncovering the experience of hope in acute stroke care has provided evidence that
      can be used to facilitate rehabilitation. METHODS: The methodology drew on the
      principles of ethnography, undertaking unstructured qualitative interviews with
      ten patients, ten multidisciplinary staff and 21 hours of participant observation
      including informal discussions with staff and patients. Data collection took
      place between November 2007 and November 2008. FINDINGS: Four themes were
      identified: suffering, struggling with no hope and despair, hope for recovery and
      realistic hopefulness. Hope was experienced in the context of suffering a stroke
      demonstrated as loss of function, loss of mental capacity and dependency.
      Patients struggled to maintain a sense of hopefulness while feeling close to a
      slippery slope towards despair and death. Hope was expressed as a strong desire
      to recover, get back to normal and a time to reflect on their lives so far. Staff
      identified realistic hopefulness as focused on keeping things real while
      balancing giving hope and avoiding false hope. CONCLUSION: Hope is placed within
      the emotional challenges of suffering and struggle inherent in recovery from
      stroke. The staff work with patients' hopes but offer realistic hopefulness as a
      practical strategy for recovery. Further interventions are required for working
      with feelings of despair or no hope.

PMID- 22150291
TI  - Skin grafts in the periocular region without a bolstered dressing.
AB  - PURPOSE: To assess success and intervention rates for full-thickness skin grafts
      in the periocular region without the use of a sutured bolster dressing. METHODS:
      A clinical assessment of the long-term outcome in consecutive patients who
      underwent skin-grafting procedures without a bolstered dressing between 2003 and
      2009 under a single surgeon (BP). All patients were independently clinically
      evaluated by two surgeons to assess final graft outcome. Data was collected on
      demographics, surgical indication, surgical technique, follow-up time and
      complications. The final clinical evaluation assessed graft thickness, color,
      contracture and lid position. Patient satisfaction was assessed using a visual
      analogue scale. Mean follow-up time was 27 months. RESULTS: Clinical review was
      possible in 35 out of 47 grafts carried out during the study period. There were
      no cases of postoperative graft ischemia or failure. Hematoma not affecting the
      final outcome occurred in two grafts and graft contraction requiring intervention
      occurred in only one patient. Patient satisfaction was high with an average score
      of 9/10. CONCLUSION: We report a high success rate for periocular skin grafts
      without the use of a bolstered dressing. The use of a bolster increases operating
      time, postoperative care and is possibly less acceptable to the patient. We
      suggest that that in most cases the use of a bolster is not necessary for
      periocular skin grafts.

PMID- 22150292
TI  - Personal and family perfectionism of Taiwanese college students: relationships
      with depression, self-esteem, achievement motivation, and academic grades.
AB  - An increasing number of perfectionism studies have been conducted across
      different countries outside of the Western framework. Using an international
      egalitarian approach that adopts indigenous frameworks and concepts from the
      cultural context of the population studied is imperative. This study examines
      different groups of perfectionists with a sample of 348 Taiwanese college
      students, emphasizing the collectivistic culture. In particular, this is a follow
      up study to further explore characteristics of a group with low standards/high
      discrepancy--a feeling that they are not good enough despite having low standards
      -found in a previous study with Taiwanese students. More specifically, this study
      investigates whether the source of the high discrepancy scores among this group
      is related to having higher perfectionistic standards from their family.
      Perfectionism was examined not only from a personal/individualistic perspective,
      but also from a familistic dimension to reflect Taiwanese collectivistic cultural
      values. Results partially supported the hypotheses--this group reported having
      higher family discrepancy, but not family standards, than nonperfectionists.
      However, this group of participants reported lower academic grades, which implies
      the possibility of their discrepancy being associated with poorer performance.
      Four cluster groups--adaptive perfectionists, maladaptive perfectionists,
      nonperfectionists, and those with low standards/high discrepancy--were compared
      on their levels of depression, self-esteem, achievement motivation, and academic
      grades. Maladaptive perfectionists reported the highest depression level, while
      adaptive perfectionists reported the highest self-esteem. Results also show that
      aspects of personal perfectionism and family perfectionism related to self-esteem
      differently among this sample. Findings and implications are discussed with
      consideration of the collectivistic cultural context in Taiwan.

PMID- 22150293
TI  - What can be learned about the impact of diabetes on hospital admissions from
      routinely recorded data?
AB  - AIM: To determine whether inpatients with diabetes have different lengths of
      stay, day-case listing rates or emergency readmission rates compared with those
      without diabetes receiving similar treatment. METHOD: English 2007-2008 Hospital
      Episode Statistics were analysed alone and after linkage to the 1.6 million
      people included in the 2007-2008 English National Diabetes Audit. Length of stay,
      day-case listing rates and emergency readmission rates were compared between
      those with and without diabetes by Health Resource Group chapter. Using
      univariate and multivariate statistics, the potential influences of age, sex,
      social deprivation, type and complexity of admission were considered. RESULTS: Of
      all inpatient spells in Hospital Episode Statistics, 6.2% have diabetes coded at
      discharge. Substantial under-recording of diabetes has been identified-a further
      3% of inpatient spells involve people with diabetes. Inpatients with recorded
      diabetes stay in hospital for 100% longer on average, are 50% less likely to be
      treated as day cases and are almost 100% more likely to be readmitted as an
      emergency. The adverse impact of diabetes on length of stay was similar to that
      for chronic obstructive pulmonary disease. Most of this adverse effect was in
      patients coded with diabetes in Hospital Episode Statistics. Multivariate
      statistical analysis showed that diabetes is independently associated with
      increased length of stay. The effect differed up to threefold between hospitals.
      CONCLUSIONS: Diabetes has an independent adverse effect on key aspects of
      hospital inpatient stays. If the lowest levels of adverse impact on inpatients
      with diabetes were more common, substantial cost savings and improved experience
      of care would be realized.

PMID- 22150294
TI  - Nipple and areolar hyperpigmentation secondary to the use of estradiol spray on
      the ipsilateral forearm skin: a report of two cases.
AB  - BACKGROUND: Metered transdermal estradiol spray may cause ipsilateral
      hyperpigmentation of the nipple and areola. CASES: Two women who were using
      transdermal estradiol spray for the treatment of postmenopausal symptoms
      developed hyperpigmentation of the ipsilateral areola and nipple. The appearance
      was variable in onset and did not appear to be related to the duration of use.
      CONCLUSION: Estradiol transdermal spray can have the rare side effect of
      ipsilateral nipple and areolar hyperpigmentation. The time of onset can vary.

PMID- 22150296
TI  - The influence of serve characteristics on performance in men's and women's high
      standard beach volleyball.
AB  - The precise influence of serve type and serve ball speed on beach volleyball
      performance is unclear. We examined the relationship between serve type and speed
      and their effectiveness during the 2008 Men's and Women's Open World Tour
      Tournament. Three hundred and seventy-eight and 375 serves performed by men and
      women respectively from the main draw tournament were analysed. Serve speed was
      recorded using a radar gun. Two expert observers recorded serve speed, serve
      mode, serve effectiveness and rally outcome. There was no relationship between
      serve speed and its effectiveness for men (r = -0.047, P > 0.05) and for women (r
      = -0.048, P > 0.05). However, there was a relationship between serve ball speed
      and its effectiveness both for men and women, when speed was categorised into
      three groups. There was a better balance between negative and positive outcomes
      at medium speeds for men and at low and high speeds for women. There was a
      relationship between ranking and serve ball speed only for women and between
      ranking and type of serve for both genders. There was no relationship between
      rally outcome and serve effectiveness. The combination of high ball speed and
      jump serve is characteristic of high ranking women but not of men.

PMID- 22150295
TI  - Mediators of adverse birth outcomes among socially disadvantaged women.
AB  - BACKGROUND: Numerous studies find that socially disadvantaged women are more
      likely than socially advantaged women to deliver infants that weigh less than
      normal and/or are born weeks prior to their due date. However, little is known
      about the pathways that link maternal social disadvantage to birth outcomes.
      Using data from a prospective cohort study, we examined whether antenatal
      psychosocial stress, substance use, and maternal health conditions in pregnancy
      mediated the pathway between maternal social disadvantage and birth outcomes.
      METHODS: Analyses used structural equation modeling to examine data from a
      community clinic-based sample (n=2168) of pregnant women who completed
      questionnaires assessing psychosocial functioning and health behaviors as well as
      sociodemographic characteristics, which were matched with subsequent birth
      outcome data. RESULTS: Analyses revealed maternal social disadvantage predicted
      poorer birth outcomes through a mediated pathway including maternal health
      conditions in pregnancy. CONCLUSIONS: The findings demonstrate that maternal
      social disadvantage is associated with poor health status in pregnancy, which in
      turn adversely affects birth outcomes. Results argue for more systematic
      attention to the roles of social disadvantage, including life course perspectives
      that trace social disadvantage prior to and through pregnancy.

PMID- 22150297
TI  - Contribution of a cyclonic-based liquid air collector for detecting Aspergillus
      fumigatus by QPCR in air samples.

PMID- 22150298
TI  - A scanning electron microscope based new method for determining degree of
      substitution of sodium carboxymethyl cellulose.
AB  - Na-CMC or sodium carboxylmethyl cellulose is a water soluble anionic polymer
      obtained by introducing carboxymethyl groups along the cellulose chain. Na-CMC is
      usually synthesized by the alkali catalyzed reaction of cellulose with
      monochloroacetic acid. The functional properties of Na-CMC depend on the degree
      of substitution of the cellulose structure (i.e. how many of the hydroxyl groups
      are substituted per monomer unit), and also on the chain length of the cellulose
      backbone. The degree of substitution of Na-CMC is usually determined according to
      ASTM D1439 which evolves the conversion of the Na-CMC to free acid then again
      forming Na-CMC by adding excess alkali and finally titrating the excess alkali
      with standard hydrochloric acid (0.3 N). The used volume of the standard alkali
      determines the degree of substitution. These existing chemical methods for
      determining the degree of substitution are not very convenient and very time
      consuming involving the use of hazardous chemicals. In this research, we have
      evaluated that the scanning electron microscope equipped with Energy Dispersive X
      Ray Analysis can be used to directly determine the degree of substitution.

PMID- 22150299
TI  - Acute clinical evaluation of a left ventricular automatic threshold determination
      algorithm based on evoked response sensing.
AB  - INTRODUCTION: Automatic pacing threshold (AT) testing may simplify device follow
      up and improve device longevity. This study's objective was to evaluate the
      performance of a left ventricular (LV) evoked response sensing-based AT
      algorithm, for cardiac resynchronization therapy (CRT) devices. METHODS: Patients
      scheduled for CRT-D/P implant were enrolled. A manual step-down threshold test
      and a Left Ventricular Automatic Threshold (LVAT) test in each of four pacing
      vectors-LVTip->Can, LVTip->right ventricle (RV), = LVRing->Can, and LVRing->RV
      were conducted. Patients were randomized to either 0.4-ms or 1.0-ms pacing pulse
      width and in the manual and LVAT test order. A blinded core lab
      electrophysiologist (EP) determined the threshold using the surface
      electrocardiogram (gold standard). RESULTS: Data from 70 patients were analyzed.
      Bipolar LV leads from three major manufacturers were used. A total of 273 AT
      tests were performed; 12 AT tests did not result in a threshold due to improper
      testing conditions. Of 261 eligible tests, 234 AT tests (89.6%) returned a
      threshold measurement. Of the 234 tests, in 233 tests (99.5%) the algorithm
      determined threshold matched the EP-determined threshold for that test. A total
      of 16,689 capture and 526 noncapture beats were collected and the accuracy for
      detecting capture and noncapture were 98.5% and 99.7% with a two-sided 95%
      confidence level of (98.4%, 98.7%) and (99.4%, 100%), respectively. No AT
      threshold measurement was lower than the EP-determined threshold. CONCLUSION: In
      this study, the results suggest that the LVAT algorithm is accurate at
      determining pacing thresholds in multiple pacing configurations and a wide range
      of LV leads in CRT-D/P patients.

PMID- 22150300
TI  - Development of a fast, simple profiling method for sample screening using high
      resolution melting (HRM) of STRs.
AB  - A screening assay has been developed to provide preliminary individualization of
      crime scene samples thus eliminating expensive, time-consuming short tandem
      repeat (STR) profiling of nonprobative samples. High resolution melting performed
      in a real-time PCR instrument is used to detect the slight melting differences
      between the length and sequence variations of 22 forensic STRs. Three STRs (vWA,
      D18S51, THO1) were chosen to develop an assay which was optimized for Mg++
      concentration, annealing/extension time/temperature, assay volume, and bovine
      serum albumin addition. The assay was tested for reproducibility, uniformity for
      genotype, melting profile consistency, effects of inhibitors, and mixture
      effects. The assay could be used to determine DNA concentration when a standard
      curve is run simultaneously. Calculations of costs show that the assay can save
      significant time and money for a crime with many samples or suspects.

PMID- 22150302
TI  - Preface: special issue on critical reviews in leukemogenesis.

PMID- 22150301
TI  - Diagnostic validity of age and education corrections for the Mini-Mental State
      Examination in older African Americans.
AB  - OBJECTIVES: To investigate whether demographic (age and education) adjustments
      for the Mini-Mental State Examination (MMSE) attenuate mean score discrepancies
      between African-American and Caucasian adults and whether demographically
      adjusted MMSE scores improve the diagnostic classification accuracy of dementia
      in African-American adults over unadjusted MMSE scores. DESIGN: Cross-sectional
      study. SETTING: Community-dwelling adults participating in the Mayo Clinic
      Alzheimer's Disease Patient Registry and Alzheimer's Disease Research Center.
      PARTICIPANTS: Three thousand two hundred fifty-four adults (2,819 Caucasian, 435
      African American) aged 60 and older. MEASUREMENTS: MMSE score at study entry.
      RESULTS: African-American adults had significantly lower unadjusted MMSE scores
      (23.0 +/- 7.4) than Caucasian adults (25.3 +/- 5.4). This discrepancy persisted
      despite adjustment of MMSE scores for age and years of education using
      established regression weights or newly derived weights. Controlling for dementia
      severity at baseline and adjusting MMSE scores for age and quality of education
      attenuated this discrepancy. In African-American adults, an age- and education
      adjusted MMSE cut score of 23/24 provided optimal dementia classification
      accuracy, but this represented only a modest improvement over an unadjusted MMSE
      cut score of 22/23. The posterior probability of dementia in African-American
      adults is presented for various unadjusted MMSE cut scores and prevalence rates
      of dementia. CONCLUSION: Age, dementia severity at study entry, and quality of
      educational experience are important explanatory factors in understanding the
      existing discrepancies in MMSE performance between Caucasian and African-American
      adults. These findings support the use of unadjusted MMSE scores when screening
      older African Americans for dementia, with an unadjusted MMSE cut score of 22/23
      yielding optimal classification accuracy.

PMID- 22150303
TI  - Ikaros and tumor suppression in acute lymphoblastic leukemia.
AB  - The Ikzf1 gene encodes Ikaros-a DNA-binding zinc finger protein. Ikaros functions
      as a regulator of gene expression and chromatin remodeling. The biological roles
      of Ikaros include regulating the development and function of the immune system
      and acting as a master regulator of hematopoietic differentiation. Genomic
      profiling studies identified Ikzf1 as an important tumor suppressor in acute
      lymphoblastic leukemia (ALL), particularly in ALL that is associated with poor
      prognosis. This review summarizes currently available data regarding the
      structure and function of Ikaros, the clinical relevance of genetic inactivation
      of Ikzf1, and signal transduction pathways that regulate Ikaros function.

PMID- 22150304
TI  - Understanding the biology of CRLF2-overexpressing acute lymphoblastic leukemia.
AB  - Recent genomic analyses of childhood and adult B-precursor acute lymphoblastic
      leukemia (ALL) samples have identified novel genetic alterations in essential
      lymphoid development and signal transduction pathways, providing insight into the
      pathogenesis of high-risk ALL associated with treatment failure. Particular
      advances have been made in unraveling the genetics of ALL associated with
      overexpression of the cytokine receptor-like factor 2 gene (CRLF2), which is
      frequently accompanied by simultaneous activating mutations in genes encoding
      Ikaros (IKZF1), Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2), and/or the IL-7
      receptor alpha chain (IL7RA). Children and adults with high-risk CRLF2
      overexpressing ALL have high rates of relapse and dismal overall survival.
      Various groups have thus attempted to characterize the biochemical consequences
      of these genetic lesions via preclinical models with the goal of identifying
      targets for new therapies. These studies provide early data suggesting the
      promise of signal transduction inhibitors (STIs) of the JAK/STAT and PI3K
      pathways for CRLF2-overexpressing ALL. Additional research efforts continue to
      elucidate these aberrant signaling networks to provide rationale for bringing
      STIs into the clinic for these high-risk patients. This review highlights the
      current knowledge of the incidence, prognostic significance, and biology of CRLF2
      overexpressing ALL and future directions for development of targeted therapies.

PMID- 22150305
TI  - Myeloid leukemia in Down syndrome.
AB  - Although adults with Down syndrome (DS) show a decreased incidence of cancer
      compared to individuals without DS, children with DS are at an increased risk of
      leukemia. Nearly half of these childhood leukemias are classified as acute
      megakaryoblastic leukemia (AMKL), a relatively rare subtype of acute myeloid
      leukemia (AML). Here, we summarize the clinical features of myeloid leukemia in
      DS, review recent research on the mechanisms of leukemogenesis, including the
      roles of GATA1 mutations and trisomy 21, and discuss treatment strategies. Given
      that trisomy 21 is a relatively common event in hematologic malignancies, greater
      knowledge of how the genes on chromosome 21 contribute to DS-AMKL will increase
      our understanding of a broader class of patients with leukemia.

PMID- 22150306
TI  - CREB and leukemogenesis.
AB  - Acute myeloid leukemia (AML) is one of the most common leukemias with a 20% 5
      year event-free survival in adults and 50% overall survival in children, despite
      aggressive chemotherapy treatment and bone marrow transplantation. The incidence
      and mortality rates for acute leukemia have only slightly decreased over the last
      20 years, and therefore greater understanding of the molecular mechanisms
      associated with leukemic progression is needed. To this end, a number of
      transcription factors that appear to play a central role in leukemogenesis are
      being investigated; among them is the cAMP response element binding protein
      (CREB). CREB is a transcription factor that can regulate downstream targets
      involving in various cellular functions including cell proliferation, survival,
      and differentiation. In several studies, the majority of bone marrow samples from
      patients with acute lymphoid and myeloid leukemia demonstrate CREB
      overexpression. Moreover, CREB overexpression is associated with a poor outcome
      in AML patients. This review summarizes the role of CREB in leukemogenesis.

PMID- 22150307
TI  - TAM receptors in leukemia: expression, signaling, and therapeutic implications.
AB  - In the past 30 years there has been remarkable progress in the treatment of
      leukemia and lymphoma. However, current treatments are largely ineffective
      against relapsed leukemia and, in the case of pediatric patients, are often
      associated with severe long-term toxicities. Thus, there continues to be a
      critical need for the development of effective biologically targeted therapies.
      The TAM family of receptor tyrosine kinases-Tyro3, Axl, and Mer-plays an
      important role in normal hematopoiesis, including natural killer cell maturation,
      macrophage function, and platelet activation and signaling. Furthermore, TAM
      receptor activation leads to upregulation of pro-survival and proliferation
      signaling pathways, and aberrant TAM receptor expression contributes to cancer
      development, including myeloid and lymphoid leukemia. This review summarizes the
      role of TAM receptors in leukemia. We outline TAM receptor expression patterns in
      different forms of leukemia, describe potential mechanisms leading to their
      overexpression, and delineate the signaling pathways downstream of receptor
      activation that have been implicated in leukemogenesis. Finally, we discuss the
      current research focused on inhibitors against these receptors in an effort to
      develop new therapeutic strategies for leukemia.

PMID- 22150308
TI  - The role of Hox proteins in leukemogenesis: insights into key regulatory events
      in hematopoiesis.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease with highly variable
      prognoses. Identification of recurring chromosomal translocations provides some
      prognostic information for individual AML subjects. Population based gene
      expression profiling studies also identified abnormalities relevant to prognosis.
      Such studies associate increased expression of a set of homeodomain transcription
      factors with poor prognosis in AML. This set includes HoxB3, B4, A7-11 and Meis1,
      which are dysregulated as a group in the bone marrow in poor prognosis AML.
      Aberrant expression of these homeodomain transcription factors is found in AML
      with chromosomal translocations involving the MLL, MYST3 and CREBBP genes, and in
      a poor prognosis subset with normal cytogenetics. Studies in murine models
      suggest that Hox protein overexpression is functionally significant for myeloid
      malignancies. Overexpression of individual Hox proteins expanded various bone
      marrow populations in vitro, leading to myeloproliferation and in some cases
      differentiation block and AML in vivo. Therefore, dysregulated expression of key
      Hox target genes may contribute to adverse prognosis in AML. Identification of
      these genes will provide insights into the pathobiology of prognosis in AML.
      Studies are beginning to identify Hox target genes which may be rational targets
      for therapeutic approaches to this poor prognosis leukemia subset.

PMID- 22150309
TI  - RUNX1 mutations in clonal myeloid disorders: from conventional cytogenetics to
      next generation sequencing, a story 40 years in the making.
AB  - Translocations and mutations in the core binding factor genes, RUNX1 or CBFB, are
      found in acute myeloid and lymphocytic leukemia, therapy-related myeloid
      leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and in
      familial platelet disorder with predisposition to acute myeloid leukemia. Here we
      review the biochemical and biological properties of the normal Runx1 protein,
      discuss the nature of RUNX1 mutations in myeloid leukemia, their prognostic
      significance, and the mutations that cooperate or co-exist with them in these
      various diseases.

PMID- 22150311
TI  - Targeting NOTCH1 in hematopoietic malignancy.
AB  - NOTCH1 is a well-validated target in hematopoietic malignancy, with NOTCH1
      activating mutations identified in more than 50% of T-cell acute lymphoblastic
      leukemias. Moreover, a recent report has identified NOTCH1 activating mutations
      in 12% of chronic lymphocytic leukemias. While the frequency of NOTCH1 mutations
      and the well-documented role of this protein in the pathogenesis and maintenance
      of T-ALL support targeting NOTCH1 as a therapeutic strategy, the critical role of
      this protein in normal cell-fate specification and differentiation lead to
      complexities in its successful targeting. In this review, we will discuss
      potential approaches to targeting NOTCH1 in hematopoietic malignancies, including
      inhibition of the enzymes involved in its activation, antibodies directed against
      either the receptor or its ligands, and direct interference with the NOTCH1
      transcriptional complex. Moreover, we will discuss the challenges to each of
      these approaches as well as potential solutions to overcoming these difficulties.

PMID- 22150310
TI  - C/EBPalpha dysregulation in AML and ALL.
AB  - The transcription factor CCAAT/enhancer binding protein a (C/EBPalpha) is a
      critical regulator of myeloid development, directing granulocyte, and monocyte
      differentiation. As such, it is dysregulated in more than half of patients with
      acute myeloid leukemia (AML). C/EBPalpha expression is suppressed as result of
      common leukemia-associated genetic and epigenetic alterations such as AML1-ETO,
      BCR-ABL, FLT3-ITD, or CEBPA promoter methylation. In addition, 10-15% of patients
      with AML with intermediate risk cytogenetics are characterized by mutations of
      the CEBPA gene. Two classes of mutations are described. N-terminal changes result
      in expression of a truncated dominant negative C/EBPalphap30 isoform. C-terminal
      mutations are in-frame insertions or deletions resulting in alteration of the
      leucine zipper preventing dimerization and DNA binding. Often, patients carry
      both N- and C-terminal mutations each affecting a different allele, and a mouse
      model recapitulates the human phenotype. Patients with mutated CEBPA AML comprise
      a clinically distinct group with favorable outcome consistently seen in patients
      with biallelic mutations. In addition, C/EBP family members are aberrantly
      expressing from the immunoglobulin heavy chain locus in 2% of pre-B ALLs. This
      review summarizes the normal hematopoietic developmental pathways regulated by
      C/EBPalpha and discusses the molecular pathways involved in mutated CEBPA AML and
      ALL.

PMID- 22150313
TI  - Gadd45 stress sensors in malignancy and leukemia.
AB  - Gadd45 proteins, including Gadd45a, Gadd45b, and Gadd45g, have been implicated in
      stress signaling in response to physiological and environmental stress, including
      oncogenic stress, which can result in cell cycle arrest, DNA repair, cell
      survival, senescence, and apoptosis. The function of Gadd45 as a stress sensor is
      mediated via a complex interplay of physical interactions with other cellular
      proteins implicated in cell cycle regulation and the response of cells to stress,
      notably PCNA, p21, cdc2/cyclinB1, and the p38 and JNK stress response kinases.
      Altered expression of Gadd45 has been observed in multiple types of solid tumors
      as well as in hematopoietic malignancies. Using genetically engineered mouse
      models and bone-marrow transplantation, evidence has been obtained indicating
      that Gadd45 proteins can function to either promote or suppress tumor development
      and leukemia; this is dependent on the molecular nature of the activated oncogene
      and the cell type, via engagement of different signaling pathways.

PMID- 22150312
TI  - The role of stem cell factor SALL4 in leukemogenesis.
AB  - SALL4, a member of the SALL gene family, is one of the most important
      transcriptional regulators of stem cells. It is of particular interest to stem
      cell biologists because it is linked to the self-renewal of both embryonic stem
      cells (ESCs) and hematopoietic stem cells (HSCs), and it is involved in human
      leukemia. In ESCs, the Sall4/Oct4/Nanog core transcriptional network governs the
      self-renewal and pluripotent properties of human and murine ESCs. In normal HSCs
      and leukemic stem cells (LSCs), SALL4 is linked to three known pathways that are
      involved in self-renewal: Wnt/beta-catenin, Bmi-1, and Pten. Despite the
      important shared role of SALL4 in self-renewal of HSCs and LSCs, our recent
      studies obtained through correlating global downstream target genes and unique
      functional studies in normal versus leukemic cells have demonstrated that SALL4
      has differential effects on both pro- and anti-apoptotic pathways in normal and
      leukemic cells. Targeting SALL4, particularly when combined with the use of ABT
      737, a BCL2 antagonist, could lead to leukemic cell-specific apoptosis. This
      review summarizes our current knowledge on the SALL gene family development,
      particularly on the role of SALL4 in stem cells, as well as tumorigenesis,
      especially leukemogenesis.

PMID- 22150314
TI  - Trends in sex hormone concentrations in US males: 1988-1991 to 1999-2004.
AB  - Previous studies suggest that male testosterone concentrations have declined over
      time. To explore this in a large US population, we examined testosterone and free
      testosterone concentrations in National Health and Nutrition Examination Surveys
      (NHANES) from 1988-1991 and 1999-2004. We also examined sex hormone-binding
      globulin (SHBG), estradiol, and androstanediol glucuronide (3alpha-diol-G) over
      the same period. Non-Hispanic white, non-Hispanic black, and Mexican-American men
      from 1988-1991 and 1999-2004 NHANES surveys who were >=20 years old and had serum
      from morning blood draws were included in this analysis (1988-1991: N = 1,413;
      1999-2004: N = 902). Testosterone, estradiol and SHBG were measured by
      competitive electrochemiluminescence immunoassays and 3alpha-diol-G was measured
      by enzyme immunoassay. Free testosterone was calculated using testosterone and
      SHBG values. Adjusted mean hormone concentrations were estimated using linear
      regression, accounting for NHANES sampling weights and design, age,
      race/ethnicity, body mass index, waist circumference, alcohol use and smoking.
      Differences in adjusted mean concentrations (Delta) and two-sided p-values were
      calculated; p < 0.05 was statistically significant. Overall, 3alpha-diol-G and
      estradiol declined between 1988-1991 and 1999-2004, but there was little change
      in testosterone, free testosterone, or SHBG (Delta: 3alpha-diol-G = -1.83 ng/mL,
      p < 0.01; estradiol = -6.07 pg/mL, p < 0.01; testosterone = -0.03 ng/mL, p =
      0.75; free testosterone = -0.001 ng/mL, p = 0.67; SHBG = -1.17 nmol/L, p = 0.19).
      Stratification by age and race revealed that SHBG and 3alpha-diol-G declined
      among whites 20-44 years old (Delta: SHBG = -5.14 nmol/L, p < 0.01; 3alpha-diol-G
      = -2.89 ng/mL, p < 0.01) and free testosterone increased among blacks 20-44 years
      old (Delta: 0.014 ng/mL, p = 0.03). Estradiol declined among all ages of whites
      and Mexican-Americans. In conclusion, there was no evidence for testosterone
      decline between 1988-1991 and 1999-2004 in the US general population. Subgroup
      analyses suggest that SHBG and 3alpha-diol-G declined in young white men,
      estradiol declined in white and Mexican-American men, and free testosterone
      increased in young black men. These changes may be related to the increasing
      prevalence of reproductive disorders in young men.

PMID- 22150317
TI  - Evaluating and improving risk formulas for allocating limited budgets to
      expensive risk-reduction opportunities.
AB  - Simple risk formulas, such as risk = probability * impact, or risk = exposure *
      probability * consequence, or risk = threat * vulnerability * consequence, are
      built into many commercial risk management software products deployed in public
      and private organizations. These formulas, which we call risk indices, together
      with risk matrices, "heat maps," and other displays based on them, are widely
      used in applications such as enterprise risk management (ERM), terrorism risk
      analysis, and occupational safety. But, how well do they serve to guide
      allocation of limited risk management resources? This article evaluates and
      compares different risk indices under simplifying conditions favorable to their
      use (statistically independent, uniformly distributed values of their components;
      and noninteracting risk-reduction opportunities). Compared to an optimal
      (nonindex) approach, simple indices produce inferior resource allocations that
      for a given cost may reduce risk by as little as 60% of what the optimal
      decisions would provide, at least in our simple simulations. This article
      suggests a better risk reduction per unit cost index that achieves 98-100% of the
      maximum possible risk reduction on these problems for all budget levels except
      the smallest, which allow very few risks to be addressed. Substantial gains in
      risk reduction achieved for resources spent can be obtained on our test problems
      by using this improved index instead of simpler ones that focus only on relative
      sizes of risk (or of components of risk) in informing risk management priorities
      and allocating limited risk management resources. This work suggests the need for
      risk management tools to explicitly consider costs in prioritization activities,
      particularly in situations where budget restrictions make careful allocation of
      resources essential for achieving close-to-maximum risk-reduction benefits.

PMID- 22150316
TI  - Inhibition of Mycobacterium tuberculosis-induced signalling by transforming
      growth factor-beta in human mononuclear phagocytes.
AB  - Tuberculosis (TB) is associated with excessive production and bioactivation of
      transforming growth factor bets (TGF-beta) in situ. Here, modification of
      expression of components of plasminogen/plasmin pathway in human monocytes (MN)
      by inhibitors of TGF-beta signalling was examined. Smad3 siRNA effectively
      inhibited TGF-beta-induced urokinase plasminogen activator receptor (uPAR).
      Agents known to interfere with TGF-beta signalling, including the Smad inhibitors
      SIS3 and erythromycin derivatives, and ALK5 receptor inhibitor (SB 431542) in
      inhibition of uPAR expression in response to Mycobacterium tuberculosis (MTB)
      were examined. Inhibition by SIS3 only inhibited uPAR mRNA significantly. SIS3
      may prove to be an effective adjunct to TB therapy.

PMID- 22150318
TI  - Macromolecular and small-molecule modulation of intracellular Abeta42 aggregation
      and associated toxicity.
AB  - Abeta (amyloid beta-peptide) has a central role in AD (Alzheimer's disease) where
      neuronal toxicity is linked to its extracellular and intracellular accumulation
      as oligomeric species. Searching for molecules that attenuate Abeta aggregation
      could uncover novel therapies for AD, but most studies in mammalian cells have
      inferred aggregation indirectly by assessing levels of secreted Abeta peptide. In
      the present study we establish a mammalian cell system for the direct
      visualization of Abeta formation by expression of an Abeta(42)-EGFP (enhanced
      green fluorescent protein) fusion protein in the human embryonic kidney cell line
      T-REx293, and use this to identify both macromolecules and small molecules that
      reduce aggregation and associated cell toxicity. Thus a molecular shield protein
      AavLEA1 [Aphelenchus avenae LEA (late embryogenesis abundant) protein 1], which
      limits aggregation of proteins with expanded poly(Q) repeats, is also effective
      against Abeta(42)-EGFP when co-expressed in T-REx293 cells. A screen of
      polysaccharide and small organic molecules from medicinal plants and fungi
      reveals one candidate in each category, PS5 (polysaccharide 5) and ganoderic acid
      DM respectively, with activity against Abeta. Both PS5 and ganoderic acid DM
      probably promote Abeta aggregate clearance indirectly through the proteasome. The
      model is therefore of value to study the effects of intracellular Abeta on cell
      physiology and to identify reagents that counteract those effects.

PMID- 22150319
TI  - Buschke-Ollendorff syndrome and bilateral cutaneous syndactyly.
AB  - A 3-year-old boy presented with asymptomatic elastomas on the posterior trunk.
      Radiographic studies revealed osteopoikilosis, confirming the diagnosis of
      Buschke-Ollendorff syndrome. The patient had a history of bilateral simple
      cutaneous syndactyly, which has not been previously reported with this condition.
      Buschke-Ollendorff syndrome is a rare autosomal-dominant disorder characterized
      by connective tissue nevi and osteopoikilosis. Several associated systemic
      abnormalities have been reported, but morbidity and mortality are generally not
      affected.

PMID- 22150320
TI  - Blogging for weight loss: personal accountability, writing selves, and the weight
      loss blogosphere.
AB  - Body weight is a key concern in contemporary society, with large proportions of
      the population attempting to control their weight. However, losing weight and
      maintaining weight loss is notoriously difficult, and new strategies for weight
      loss attract significant interest. Writing about experiences of weight loss in
      online journals, or blogging, has recently expanded rapidly. Weight-loss bloggers
      typically write about daily successes and failures, report calorie consumption
      and exercise output, and post photographs of their changing bodies. Many bloggers
      openly court the surveillance of blog readers as a motivation for accountability
      to their weight-loss goals. Drawing from a sample of weight-loss blogs authored
      by women, we explore three issues arising from this practice of disclosing a
      conventionally private activity within an online public domain. First, we examine
      motivations for blogging, focusing on accountability. Secondly, we consider the
      online construction of self, exploring how weight-loss bloggers negotiate
      discourses around fatness, and rework selves as their bodies transform. Finally,
      we consider the communities of interest that form around weight-loss blogs. This
      'blogosphere' provides mutual support for weight loss. However, participating in
      online social spaces is complicated and bloggers must carefully manage issues of
      privacy and disclosure.

PMID- 22150321
TI  - Treatment of HPV infection-associated cervical condylomata acuminata with 5
      aminolevulinic acid-mediated photodynamic therapy.
AB  - The aim of this study was to investigate the efficacy of 5-aminolaevulinic acid
      (ALA)-mediated photodynamic therapy (PDT) in treatment of human papillomavirus
      (HPV)-associated cervical condylomata. A total of 56 patients with cervical and
      external condylomata lesions were recruited for this open-label study. HPV
      genotyping of exfoliated cells collected from the cervix and external lesions was
      performed. Cervical lesions were treated with PDT by applying ALA gel (10%) to
      the surface of the cervix for 4 h followed by irradiating with a 635 nm laser at
      100 J cm(-2). PDT was repeated at 2-week intervals if lesion and HPV infection
      remained. Patients were followed up for 6-24 months. Genotyping analysis revealed
      four HPV subtypes (HPV6, 11, 16 and 18). The overall complete remission rate of 1
      4 sessions of treatments was 98.2% and the corresponding HPV clearance rate was
      83.9%. Ten cases showed complete removal of cervical lesions and HPV infection
      after a single treatment. Recurrence rate was 3.6%. Adverse effects were minimal
      and no structural complications were reported. In conclusion, topical ALA PDT is
      safe and effective for eradicating cervical HPV infection and eliminating
      condylomata lesion. Its definitive role in treating cervical condylomata deserves
      further investigation.

PMID- 22150324
TI  - Transitions.

PMID- 22150322
TI  - Nuclear translocation of intracellular domain of Protogenin by proteolytic
      cleavage.
AB  - Protogenin (PRTG) is a transmembrane protein of immunoglobulin superfamily, which
      has multiple roles in embryogenesis as a receptor or an adhesion molecule. In
      this study, we present sequential proteolytic cleavage of PRTG. The cleavage
      first occurs at the extracellular domain, then at the interface of the
      transmembrane and the intracellular domain by gamma-secretase, which results in
      the release of the intracellular domain of PRTG (PRTG-ICD). PRTG-ICD contains
      putative nuclear localization signal (NLS) at its N-terminal, and translocates to
      the nucleus in cultured cells and in the neuroepithelial cells of chick embryos.
      We propose that the PRTG-ICD is cleaved by gamma-secretase and translocates to
      the nucleus, which is potentially implicated in signaling for neural
      differentiation and in cell adhesion mediated by PRTG.

PMID- 22150327
TI  - Stressing the importance of development. Interview by Kristie Nybo.

PMID- 22150328
TI  - Genome editing goes global.

PMID- 22150330
TI  - qPCR efficiency calculations.

PMID- 22150331
TI  - A qPCR-based assay to quantify oxidized guanine and other FPG-sensitive base
      lesions within telomeric DNA.
AB  - Telomere shortening is an important risk factor for cancer and accelerated aging.
      However, it is becoming evident that oxidatively damaged DNA within the telomere
      sequence may also cause telomere dysfunction. Here we describe a reliable, cost
      effective quantitative PCR (qPCR)-based method to measure the amount of oxidized
      residues within telomeric DNA that are recognized and excised by
      formamidopyridine DNA glycosylase (FPG). We also report that in an in vitro model
      of oxidative stress oxidized base lesions measured using this method are more
      prevalent within telomeric sequences. Furthermore, this method is sufficiently
      sensitive to detect changes in oxidative stress induced by zinc deficiency and
      hydrogen peroxide within the physiological range.

PMID- 22150332
TI  - Aptamer selection by high-throughput sequencing and informatic analysis.
AB  - Traditional methods for selecting aptamers require multiple rounds of selection
      and optimization in order to identify aptamers that bind with high affinity to
      their targets. Here we describe an assay that requires only one round of positive
      selection followed by high-throughput DNA sequencing and informatic analysis in
      order to select high-affinity aptamers. The assay is flexible, requires less
      hands on time, and can be used by laboratories with minimal expertise in aptamer
      biology to quickly select high-affinity aptamers to a target of interest. This
      assay has been utilized to successfully identify aptamers that bind to thrombin
      with dissociation constants in the nanomolar range.

PMID- 22150333
TI  - An improved intracellular staining protocol for efficient detection of nuclear
      proteins in YFP-expressing cells.
AB  - Intracellular staining is a widely used flow cytometry (FCM)-based technique to
      detect the expression of cytoslio nucleic antigens. However, intracellular
      staining of cells expressing cytosolic fluorescent protein (FP) markers was
      proven to be problematic as significant loss of the FP-signal was routinely
      observed. Using splenocytes harvested from mice constitutively expressing the
      enhanced yellow fluorescent proteins (YFP) as a model, we modified the widely
      used intracellular staining protocol and successfully achieved simultaneous
      detection of both the nuclear proteins and YFP in T-regulatory cells. The
      improved protocol can be used to perform antibody-based intracellular
      characterization of FP-labeled target cells, while maintaining their fluorescent
      reporter signals for easy tracing and identification.

PMID- 22150334
TI  - Computation-assisted SiteFinding- PCR for isolating flanking sequence tags in
      rice.
AB  - SiteFinding-PCR is a method for isolating flanking sequence tags (FSTs) of T-DNA
      insertion lines, but the efficiency needs to be improved. Here we report a
      computation-assisted design for the random primers used in SiteFinding- PCR. A
      short sequence, GCATG, was screened from the rice genome and used as the 3' end
      of the random primer. When applying the optimized primer for isolating FSTs from
      168 transgenic rice lines, we obtained 107 specific products, including 64 FSTs.
      The efficiency of obtaining FSTs using the modified version of SiteFinding-PCR
      increased by 73.0% compared with the method previously reported (P < 0.01, u
      test). We also provide computational results for several other plant species such
      as maize, sorghum, Arabidopsis, foxtail millet, and Brachypodium based on the
      available genome data, so that the modified method could be easily adapted to
      other species.

PMID- 22150335
TI  - A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic
      leukaemia.
AB  - The analysis of chromosomal abnormalities provides significant prognostic
      information in patients with chronic lymphocytic leukaemia (CLL), a disease with
      a highly heterogeneous clinical course. Chromosomal abnormalities commonly found
      are trisomy 12, del(13)(q14), del(11)(q22-23), del(17)(p13) and del(6)(q21).
      Translocations are present in some patients and affect regions recurrently
      involved in CLL. This report describes the clinical and pathological
      characteristics of four CLL patients showing a new recurrent chromosomal
      abnormality dic(8;17)(p11;p11), that implied loss of the TP53 gene in all cases.
      In addition, TP53 gene was mutated in three out of four patients. Mechanically,
      Low Copy Repeats (LCR) in 17p12 and 8p11 may explain the origin of the
      translocation by non-allelic homologous recombination (NAHR). Isolated
      dic(8;17)(p11;p11) in patients with mutated IGHV genes status may not have the
      same prognostic impact as other mutations or deletions affecting the TP53 gene.
      Larger series are needed to better evaluate the clinical impact of this
      chromosomal aberration during the course of the disease.

PMID- 22150336
TI  - Exploring the effect of regulatory focus on ad attitudes: the moderating roles of
      message sidedness and argument quality.
AB  - This research explores the interaction effects of message sidedness and argument
      quality of ads on how either promotion-focused or prevention-focused individuals
      engender their ad attitudes. Two hundred and forty undergraduates were randomly
      assigned to a 2 (regulatory focus: prevention-focus/promotion-focus) * 2 (message
      sidedness: one-sided messages/two-sided messages) * 2 (argument quality (AQ):
      weak/strong) between-subjects design. Results indicate that promotion-focused
      individuals tend to engender more favourable attitudes to weak AQ ads than strong
      AQ ads, whereas prevention-focused individuals tend to engender more favourable
      attitudes to strong AQ ads than weak AQ ads. In addition, results indicate more
      favourable attitudes for one-sided messages over two-sided messages for promotion
      focused individuals, as well as more favourable attitudes for two-sided messages
      over one-sided messages for prevention-focused individuals. Furthermore, one
      sided messages result in more favourable ad attitudes when linked with weak AQ
      for promotion-focused individuals; in contrast, two-sided messages elicit more
      favourable ad attitudes when linked with strong AQ for prevention-focused
      individuals. Results suggest that message sidedness and argument quality are
      closely related to regulatory focus, which has a direct impact on ad attitudes.
      Practical implications, theoretical contributions, limitations and directions for
      future research are discussed.

PMID- 22150337
TI  - Habitual rowing exercise is associated with high physical fitness without
      affecting arterial stiffness in older men.
AB  - The present study elucidated the effects of habitual rowing exercise on arterial
      stiffness and plasma levels of the vasoconstrictor endothelin-1 and the
      vasodilator nitric oxide (NO) in older men. Eleven rowers (68.0 +/- 1.6 years)
      and 11 sedentary control older men (64.9 +/- 1.1 years) were studied. Peak oxygen
      uptake (36.0 +/- 1.7 vs. 27.7 +/-1.9 ml . kg(-1) . min(-1)), leg press power
      (1346 +/- 99 vs. 1077 +/- 68 W), and HDL-cholesterol (75 +/- 5 vs. 58 +/-3 mg .
      ml(-1)) were higher and triglyceride (78 +/- 9 vs. 120 +/- 14 mg . ml(-1)) was
      lower in rowers than in control participants (all P < 0.05). Arterial stiffness
      indices (carotid beta-stiffness and cardio-ankle vascular index) and plasma
      endothelin-1 and NOx (nitrite + nitrate) levels did not differ between the two
      groups. These results suggest that habitual rowing exercise in older men is
      associated with high muscle power and aerobic capacity, and favourable blood
      lipid profile without affecting arterial stiffness or plasma levels of
      endotheline-1 and NO.

PMID- 22150338
TI  - Cardiac device-related endocarditis complicated by spinal abscess.
AB  - BACKGROUND: Infective endocarditis is the most serious manifestation of cardiac
      device infection and metastatic seeding of distant sites has been reported.
      However, the association between device-related endocarditis and spinal abscess
      has not been fully described. METHODS: We reviewed hospital records at three high
      volume cardiovascular referral centers from January 2005 to October 2010. Device
      related endocarditis was confirmed in all cases with positive blood cultures and
      transesophageal echocardiogram revealing lead and/or valvular vegetations. Six
      patients with spinal abscesses in association with device-related endocarditis
      were identified. RESULTS: A total of 384 patients met the clinical criteria for
      device-related endocarditis. Among these, infection was complicated by spinal
      abscess formation in six (1.5%) cases. The mean age of patients was 69.3 +/- 11.8
      years (47-82 years). The predominant clinical manifestations in these six
      patients included a recent history of fever (six), malaise (four), and
      neurological or meningeal signs (five). Spinal abscesses were diagnosed by
      magnetic resonance imaging in two and computed tomography scans in four of the
      cases. The causative pathogens were methicillin-resistant Staphylococcus aureus
      (three), methicillin-sensitive S. aureus (one), coagulase-negative Staphylococci
      (two), and Enterococcus fecalis (one). All patients underwent complete device
      removal with no procedure-related complications. Two patients died in the
      hospital, two were discharged with permanent neurological deficits, and the
      remaining two recovered with no permanent neurologic sequelae. CONCLUSION: Device
      related endocarditis must be considered in patients who present with a spinal
      abscess and bacteremia. Early recognition of this scenario is imperative in order
      to avoid permanent neurological sequelae and patient mortality. Early imaging,
      appropriate parenteral antimicrobial therapy, and expedited removal of all
      cardiac hardware are pivotal for optimal management.

PMID- 22150339
TI  - How haematological cancer nurses experience the threat of patients' mortality.
AB  - AIM: This article explores how cancer nurses experienced the threat of patients'
      mortality on malignant haematology units of one institution in Ontario, Canada.
      BACKGROUND: Although patients with cancer are living longer with bone marrow
      transplantations, still they face possibilities of dying due to complications
      from treatment and their disease. METHODS: Interpretive phenomenology guided the
      process. Nineteen front-line registered nurses were purposively recruited from
      two inpatient bone marrow transplant units. Focused observations and individual
      interviews were analysed. Data were collected from April to August 2007. RESULTS:
      The major findings emphasized nurses' internal conflict related to their
      simultaneous need to help patients fight their disease and to prepare them for
      the possibility of letting go. The authors used the terms 'letting go', not to
      reflect nurses' intents to abandon life but to release patients from perceived
      norms of the 'curative culture'. Nurses experienced 'bursting the bubble of hope'
      by circumstances not in their control, and were often not certain whether or not
      to respond and how to respond to the distress of patients and families about
      death and dying. When feeling reassured of meeting patients' and families'
      expectations, nurses enabled patients and families to let go when further
      treatment was futile, prevented technological intrusions, and helped patients
      have 'easier' deaths. CONCLUSION: Results suggest enhancing nurses' capacity to
      negotiate more effectively the contradictory clinical tasks of fighting disease
      and preparing patients for the end of life. In this regard, nurses may minimize
      patients' distress by providing opportunities for them to share their fears and
      have them validated.

PMID- 22150340
TI  - Progression of occupational risk management with advances in nanomaterials.

PMID- 22150341
TI  - Effect of 5% fluoride varnish application on caries among school children in
      rural Brazil: a randomized controlled trial.
AB  - OBJECTIVES: To determine the efficacy of 5% sodium fluoride (NaF) varnish
      application in reducing caries increments in the permanent dentition of rural
      Brazilian school children over the course of 12 months. METHODS: A double-blind,
      randomized, placebo-controlled trial was conducted with 379 children aged 7-14
      years who attended three schools in Brazil between January 2006 and December
      2007. During this period, each school was visited four times at 6-month interval
      for recruitment, dental examinations, and fluoride varnish applications.
      Recruited children were randomly assigned to either a treatment (5% NaF varnish,
      n = 198) or a control group (placebo, n = 181). Trained interviewers collected
      data on oral health habits and sociodemographic characteristics from the
      children. Information on the child's diet was collected through a 7-day food
      frequency diary. Caries examinations were conducted using the International
      Caries Detection and Assessment System (ICDAS). The efficacy of fluoride varnish
      application on caries prevention was reported as a preventive fraction (PF).
      Crude caries increments of decayed and filled surfaces (DFS) were compared
      between fluoride varnish and placebo groups. A generalized linear model (GLM) was
      constructed to test the differences in DFS increments between the groups after
      accounting for confounding factors. RESULTS: Of the total sample (N = 379), 210
      (55.4%) children had completed 12 months of follow-up including one or two
      applications of fluoride varnish or placebo. At the baseline examination, the
      children in the treatment and control groups presented on average 6.2 and 5.6
      DFS, respectively (P < 0.001). After 12 months of follow-up, the children in the
      varnish group showed significantly lower DFS increments than did children in the
      control group (10.8 versus 13.3; P < 0.007), with PF of 40% (95% CI: 34.3-45.7%;
      P < 0.0001). CONCLUSIONS: The results of this study suggest that applications of
      5% NaF varnish can be recommended as a public health measure for reducing caries
      incidence in this high-caries-risk population.

PMID- 22150342
TI  - The endocrine disruptors dibutyl phthalate (DBP) and diethylstilbestrol (DES)
      influence Leydig cell regeneration following ethane dimethane sulphonate
      treatment of adult male rats.
AB  - The manner by which endocrine-disrupting xenobiotics, such as phthalates, can
      induce changes in the development of the male reproductive system still remains
      largely unknown. Herein, we have explored the application of ethane dimethane
      sulphonate (EDS) to eliminate adult-type Leydig cells in the mature rat testis,
      leading to their regeneration from resident stem cells, as a novel system to
      investigate the effects of dibutyl phthalate (DBP) and diethylstilbestrol (DES)
      on adult-type Leydig cell differentiation. The advantage of this model is that
      one can study adult-type Leydig cell differentiation in vivo divorced from the
      concomitant endocrine development of puberty. In these preliminary studies, we
      show that both DBP and/or DES, given for 2 or 4 days following EDS application,
      indeed affect Leydig cell differentiation in the adult testis, largely by
      increasing early Leydig cell proliferation and possibly thereby delaying early
      differentiation. In particular, on day 27 post-EDS, a time-point when the
      differentiation trajectory appears to be most discriminating, we observe that
      both DBP and/or DES cause a fourfold increase in Leydig cell density, and a
      significant increase in the expression of the Leydig cell-specific marker
      transcripts INSL3, LH receptor, Cyp17a1 and Cyp 11a1. In conclusion, both DBP and
      DES are able to affect adult-type Leydig cells during their differentiation to
      cause a significant perturbation in their ultimate functional capacity.

PMID- 22150343
TI  - Effect of obesity on falls, injury, and disability.
AB  - OBJECTIVES: To examine the effect of obesity on the propensity of older adults to
      fall, sustain a fall-related injury, and develop disability in activities of
      daily living (ADLs) after a fall. DESIGN: Longitudinal population-based survey.
      SETTING: Five waves of the Health and Retirement Study (HRS), 1998-2006.
      PARTICIPANTS: Ten thousand seven hundred fifty-five respondents aged 65 and older
      in 31,602 person-intervals. MEASUREMENTS: Falls within any 2-year interval (9,621
      falls). Injuries requiring medical attention (3,130 injuries). Increased ADL
      disability after a fall within any 2-year interval (2,162 events). Underweight
      and three classes of obesity (body mass index (BMI) 30.0-34.9 kg/m(2) , Class 1)
      35.0-39.9 kg/m(2) , Class 2; >=40.0 kg/m(2) , Class 3), calculated from self
      reported height and weight. Self-reported presence of lower body limitation,
      pain, dizziness, or vision problems. Self-reported doctor's diagnosis of diabetes
      mellitus, stroke, or arthritis. RESULTS: Compared with normal-weight respondents,
      the odds ratios (OR) for risk of falling were 1.12 (95% confidence interval (CI)
      = 1.01-1.24) for obesity Class 1, 1.26 (95% CI = 1.05-1.51) for obesity Class 2,
      and 1.50 (95% CI = 1.21-1.86) for obesity Class 3. Conditional on falling, only
      obesity Class 3 was related to a lower propensity for a fall-related injury (OR =
      0.62, 95% CI = 0.44-0.87). Obesity Classes 1 and 2 were associated with a higher
      risk of greater ADL disability after a fall than normal-weight respondents (OR =
      1.17, 95% CI = 1.02-1.34; OR = 1.39, 95% CI = 1.10-1.75, respectively). Being
      underweight was not related to risk of falling or to reported injury or greater
      ADL limitation after a fall. The presence of measured health problems and chronic
      conditions was associated with greater risk of falling and, of those who fell,
      greater ADL limitation but not serious injury. CONCLUSION: Obesity appears to be
      associated with greater risk of falling in older adults, as well as a higher risk
      of greater ADL disability after a fall. Obesity (BMI >= 40 kg/m(2) ) may reduce
      the risk of injury from a fall. Further investigation of the mechanisms of
      obesity on falls and related health outcomes is warranted.

PMID- 22150344
TI  - Serological survey of Neospora caninum infection in cattle herds from Western
      Romania.
AB  - Serum samples from 376 randomly selected adult cattle, from 25 farms located in 3
      counties (Arad, Bihor, and Timis) from western Romania, were sampled for Neospora
      caninum antibodies using a commercial ELISA-kit. Seroprevalence values and risk
      factors for neosporosis (cow age, breed, herd size, farming system, previous
      abortion, and number of farm dogs) were examined using a generalized linear mixed
      model with a binomial distribution. Overall, the seroprevalence of N. caninum was
      27.7% (104/376) with a prevalence of 27.9% (24/86) in Arad, 26.9% (25/93) in
      Bihor, and 27.9% (55/197) in Timis. Of 25 cattle herds, 23 were seropositive with
      a prevalence ranging from 10.0 to 52.2%. No correlation was found between N.
      caninum seropositivity and age, breed, herd size, breeding system, and previous
      abortion. The number of farm dogs was the only factor (P(Wald)  =  0.03)
      positively associated with seroprevalence in cows and can be considered the risk
      factor in the acquiring of infection. The present work is the first regarding
      serological evidence of N. caninum infection in cattle from western Romania.

PMID- 22150345
TI  - Persistent fasting hyperglycaemia is more predictive of type 2 diabetes than
      transient fasting hyperglycaemia.
AB  - AIMS: We investigated the value of persistent fasting hyperglycaemia as assessed
      by repeated elevated fasting plasma glucose in predicting the progression to
      diabetes. METHODS: A retrospective cohort study was conducted from 1998 to 2006
      inclusive among 7929 persons (37,742 person-years), with a mean age of 53.0 years
      at baseline. The cumulative incidence of diabetes was measured. A baseline and
      follow-up fasting plasma glucose were categorized as normal fasting glucose (<
      5.56 mmol/l), or impaired fasting glucose (5.56-6.94 mmol/l). RESULTS: The
      cumulative incidence and incidence density of diabetes were 3.5% (275 cases) and
      7.3 per 1000 person-years over a mean follow-up period of 4.8 years. The
      cumulative incidence of diabetes among subjects with impaired fasting glucose at
      both previous examinations (persistent impaired fasting glucose) was 30.4%
      (222/1518) compared with 0.6% (15/5063) of those with normal fasting glucose at
      both baseline and initial follow-up. The hazard ratios to develop diabetes,
      adjusted for possible confounders, was 37.10 (95% CI, 21.6-63.7) for persistent
      impaired fasting glucose versus persistent normal fasting glucose. Persistent
      impaired fasting glucose predicted diabetes at 80.7% (222/275) sensitivity and
      83.1% (6358/7654) specificity, whereas first baseline impaired fasting glucose
      only predicted diabetes at 86.9% (239/275) sensitivity and 74.9% (5730/7654)
      specificity. The model using both previous fasting plasma glucose levels had a
      greater AUROC (area under receiver operating characteristic) than that using
      first baseline fasting plasma glucose only (0.92 vs. 0.88; P < 0.001).
      CONCLUSIONS: Repeated measurements of fasting plasma glucose better predicts
      incidence of diabetes than a single test. In particular, persistent fasting
      hyperglycaemia adds more substantial precision to the prediction of future
      diabetes than transient impaired fasting glucose. This combination is cost
      efficient and may be practical for early detection of high-risk individuals.

PMID- 22150346
TI  - Mosaic pigmentation disorders and associated syndromes.

PMID- 22150347
TI  - Nerve damage assessment following implant placement in human cadaver jaws: an ex
      vivo comparative study.
AB  - The present study compared the use of cone beam computerized tomography (CBCT)
      images and intra-oral radiographs in the placement of final implant drills in
      terms of nerve damage to cadaver mandibles. Twelve cadaver hemimandibles obtained
      from 6 cadavers were used. Right hemimandibles were imaged using peri-apical
      radiography and left hemimandibles using CBCT, and the images obtained were used
      in treatment planning for the placement of implant drills (22 for each modality,
      for a total of 44 final drills). Specimens were dissected, and the distances
      between the apex of the final implant drill and the inferior alveolar
      neurovascular bundle and incisive nerve were measured using a digital calliper.
      Nerves were assessed as damaged or not damaged, and the Chi-square test was used
      to compare nerve damage between modalities (P < 0.05). Nerve damage occurred with
      7 final drills placed based on peri-apical radiography (31.8%) and 1 final drill
      placed using CBCT images (4.5%). The difference in nerve damage between imaging
      modalities was statistically significant (P = 0.023), with CBCT outperforming
      intraoral film in the placement of final implant drills ex vivo. In order to
      prevent nerve damage, CBCT is recommended as the principal imaging modality for
      pre-implant assessment.

PMID- 22150348
TI  - Investigative studies into the recovery of DNA from improvised explosive device
      containers.
AB  - Apprehending those who utilize improvised explosive devices (IEDs) is a national
      priority owing to their use both domestically and abroad. IEDs are often
      concealed in bags, boxes, or backpacks to prevent their detection. Given this,
      the goal of the research presented was to identify IED handlers through postblast
      DNA recovery from IED containers. Study participants were asked to use backpacks
      for 11 days, after which they served as containers for pipe bombs. Eleven
      postdeflagration backpack regions likely to be handled were swabbed and analyzed
      via mini-short tandem repeats (miniSTRs) and alleles were called blind. An
      experimental consensus method was examined in which profiles from all regions
      were considered, to help identify spurious drop-in/out. Results were correct for
      all loci, except one that remained ambiguous. The results show that recovering
      DNA from IED containers is a viable approach for aiding in the identification of
      those who may have been involved in an IED event.

PMID- 22150349
TI  - Constraining groundwater modeling with magnetic resonance soundings.
AB  - Magnetic resonance sounding (MRS) is a noninvasive geophysical method that allows
      estimating the free water content and transmissivity of aquifers. In this
      article, the ability of MRS to improve the reliability of a numerical groundwater
      model is assessed. Thirty-five sites were investigated by MRS over a ~5000 km(2) 
      domain of the sedimentary Continental Terminal aquifer in SW Niger. Time domain
      electromagnetic soundings were jointly carried out to estimate the aquifer
      thickness. A groundwater model was previously built for this section of the
      aquifer and forced by the outputs from a distributed surface hydrology model, to
      simulate the observed long-term (1992 to 2003) rise in the water table.
      Uncertainty analysis had shown that independent estimates of the free water
      content and transmissivity values of the aquifer would facilitate cross
      evaluation of the surface-water and groundwater models. MRS results indicate
      ranges for permeability (K = 1 * 10(-5)  to 3 * 10(-4)  m/s) and for free water
      content (w = 5% to 23% m(3) /m(3) ) narrowed by two orders of magnitude (K) and
      by ~50% (w), respectively, compared to the ranges of permeability and specific
      yield values previously considered. These shorter parameter ranges result in a
      reduction in the model's equifinality (whereby multiple combinations of model's
      parameters are able to represent the same observed piezometric levels), allowing
      a better constrained estimate to be derived for net aquifer recharge (~22
      mm/year).

PMID- 22150350
TI  - A comparison of the compressive strength of various distal locking screw options
      in the treatment of tibia fractures with intramedullary nails.
AB  - Treatment of distal metaphyseal tibia fractures is often challenging. Newer
      tibial intramedullary (IM) nails are designed with a wider variety of distal
      locking options to offer greater stability in treating these fractures. In this
      study we attempted to determine the most biomechanically stable number and
      configuration of distal locking screws when treating distal metaphyseal tibia
      fractures with IM nails. A transverse osteotomy was created 4 cm from the tibial
      plafond in identical composite saw bones models (Type 43A fracture) as well as in
      human cadaveric bones. Each specimen was nailed using a tibial nail (Stryker T2).
      Distal locking was performed in one of the three configurations: (a) Group I: two
      screws in the medial lateral (ML) direction; (b) Group II: one ML screw and one
      screw in the anterior posterior (AP) direction; (c) Group 111: two ML screws and
      one AP screw. The specimens were then mounted onto a uniaxial material testing
      machine (Instron) and tested in compression. Our results showed that there was no
      statistical difference in the load-carrying capacity of Group 1 and Group II.
      This suggests that the treating surgeon can choose either of these two
      configurations depending on the wound or other considerations without sacrificing
      the compressive load-carrying capacity of the IM nail fixation. The load-carrying
      capacity of the Group III samples with these locking screws was higher than those
      of Group I & II, although this difference was not statistically significant. This
      work is being continued to compare the load-carrying capacity of the bone samples
      with the cortical thickness of bone. We also plan to examine the relationship
      between the load-carrying capacity of these surgical constructs with the bone
      mineral density of the metaphysis of these tibial specimens.

PMID- 22150351
TI  - Tibial shaft fracture after removal of an ACE tibial nail.
AB  - Intramedullary interlocking nailing is the gold standard method for treatment of
      tibial shaft fractures. Thus, the growing use of the intramedullary nailing
      resulted in an increased number of tibial nails removal procedures in daily
      clinical practice. Despite adequate surgeon experience, the removal of tibial
      intramedullary nails is not without complications. One of the commonly used nails
      is the ACE (DePuy Orthopaedics, Inc., Warsaw, IN, USA). The purpose of this paper
      is to report such a complication following the removal procedure and review the
      pertinent literature. A 39-year-old female who had sustained a lower-third tibial
      fracture was treated with an intramedullary nail 5 years ago. Despite her
      unremarkable follow-up, for personal reasons, a removal procedure was planned.
      Two undisplaced fractures were observed in the postoperative radiological
      evaluation. The potential complications of the removal of intramedullary nailing
      of the tibia should be considered by both physician and patient.

PMID- 22150352
TI  - Fixed versus mobile bearing knee arthroplasty: a review of kinematics and
      results.
AB  - There are several total knee arthroplasty designs available with wide variation
      in features. The long-term results of total knee replacement with a fixed bearing
      design have shown a high degree of clinical success. However, implant loosening
      and polyethylene wear became recognized as long-term causes of late failure.
      Mobile bearing knee replacements were designed to create a durable surface
      articulation by using a polyethylene insert that articulates with a metallic
      femoral component and a metallic tibial tray. The purpose of this article is to
      review clinical and basic scientific studies comparing the clinical results, the
      biomechanical features, and the kinematic patterns of fixed versus mobile bearing
      knee designs. Beside the fact that in vitro kinematic studies have shown reduced
      polyethylene wear in mobile bearings due to increased implant conformity and
      reduced polyethylene contact stresses, which should hypothetically prolong
      polyethylene life, various independent studies for both mobile bearing and fixed
      bearing prostheses have documented results that are comparable in terms of
      survival and performance.

PMID- 22150353
TI  - Long-term complications of mesh repairs for abdominal-wall hernias.
AB  - The use of prosthetic materials in repair of abdominal-wall hernias can lower the
      risk of hernia recurrence. Therefore, large numbers of meshes are used worldwide
      every year. All types of meshes on the market have the potential to cause certain
      complications, such as fistula formation, migration, infection, and rejection.
      These long-term, clinical complications, although rare, can be serious. For this
      reason, we aim to provide a systematic review on these adverse effects. A PubMed
      search covering the last 20 years was done to obtain articles reporting these
      long-term effects. After searches with selected keywords, and careful evaluation
      of the resulting articles, 64 articles reporting specific long-term complications
      were selected and set aside for analysis. Most of the articles were case reports
      and retrospective analyses (61/64). No evidence-based data exist regarding
      prevention of these late complications.

PMID- 22150354
TI  - Improving the accuracy of acetabular cup implantation using a bulls-eye spirit
      level.
AB  - Acetabular introducers have a built-in inclination of 45 degrees to the handle
      shaft. With patients in the lateral position, surgeons aim to align the
      introducer shaft vertical to the floor to implant the acetabulum at 45 degrees.
      We aimed to determine if a bulls-eye spirit level attached to an introducer
      improved the accuracy of implantation. A small circular bulls-eye spirit level
      was attached to the handle of an acetabular introducer. A saw bone hemipelvis was
      fixed to a horizontal, flat surface. A cement substitute was placed in the
      acetabulum and subjects were asked to implant a polyethylene cup, aiming to
      obtain an angle of inclination of 45 degrees. Two attempts were made with the
      spirit level masked and two with it unmasked. The distance of the air bubble from
      the spirit level's center was recorded by a single assessor. The angle of
      inclination of the acetabular component was then calculated. Subjects included
      both orthopedic consultants and trainees. Twenty-five subjects completed the
      study. Accuracy of acetabular implantation when using the unmasked spirit level
      improved significantly in all grades of surgeon. With the spirit level masked, 12
      out of 50 attempts were accurate at 45 degrees inclination; 11 out of 50 attempts
      were "open," with greater than 45 degrees of inclination, and 27 were "closed,"
      with less than 45 degrees. With the spirit level visible, all subjects achieved
      an inclination angle of exactly 45 degrees. A simple device attached to the
      handle of an acetabular introducer can significantly improve the accuracy of
      implantation of a cemented cup into a saw bone pelvis in the lateral position.

PMID- 22150355
TI  - Joint arthroplasty and infection: where do we stand?
AB  - With the field of orthopedic surgery making tremendous advances, no one arena has
      changed more dramatically then total joint arthroplasty. While this kind of
      surgery has improved quality of life for many patients, it is not without
      complications. When they do occur, these complications can be devastating and
      inflict immense burden on patients and the society. Currently, the rate of
      periprosthetic joint infection ranges from 0.25% to 2.0%. As the number of total
      joint arthroplasty procedures is expected to rise considerably, these percentages
      will impose a financial burden on the field of adult reconstruction. The purpose
      of our paper is to discuss preventative measures that can be taken to curtail
      infections, the proper diagnosis of such infections, and the appropriate
      treatment options.

PMID- 22150356
TI  - Radiation-induced sarcomas.
AB  - Radiation-induced sarcomas are rare, high-grade sarcomas that may arise within
      the radiation volume at a mean latency period of 3-55 years after radiation
      therapy, doses of which range from 45 to 60 Gy. Radiation-induced osteosarcomas,
      fibrosarcomas, and malignant fibrous histiocytomas are the most common. Extensive
      surgery with microscopically negative-margin resection, or amputation is
      recommended for improved survival. Adjuvant radiation therapy and chemotherapy
      have not been shown to improve survival rates significantly. The prognosis is
      poor.

PMID- 22150357
TI  - Prosthetic mammoplasty sensitivity syndrome: a case for causation.
AB  - Treatment of patients experiencing adverse health effects following prosthetic
      mammoplasty has suffered from a lack of an acknowledgment of a causal
      relationship to their breast prosthetic devices. Case reports and case series
      showing an association between adverse health effects and breast implants have
      been routinely dismissed as anecdotal, and epidemiological studies have been
      considered necessary to prove causality. We show that epidemiological research is
      not necessary for establishing a causal relationship, and one properly documented
      case can be, in fact, all that is needed to show causation. Presently in the peer
      reviewed literature there exists a substantial scientifically sound body of data
      showing an association between breast implants and adverse health effects. Ample
      evidence has shown that exposure to the five common types of breast implants
      outlined, i.e., silicone gel filled, saline filled, double lumen, polyurethane
      coated, and cohesive silicone, has caused adverse health effects in humans.
      Prosthetic mammoplasty sensitivity syndrome (PMSS) is the proposed term to
      describe the disease processes documented in the literature that has a causal
      relationship to breast implants.

PMID- 22150358
TI  - Intra-operative fenestration of stent grafts: a note of caution based upon
      preliminary in vitro observations.
AB  - Intra-operative fenestrations of stent grafts make more frail and elderly
      patients amenable to endovascular surgery but require further assessment of the
      viability of currently used experimental techniques. Four types of polyester
      fabrics currently employed in stent grafts were exposed in vitro to various
      protocols of fenestration: cutting, trocaring, and cantering. The resulting
      fenestrations were examined by gross observation, light microscopy, and scanning
      electron microscopy. Blunt fenestration by scissors and sharp penetration led to
      unpredictable apertures, impairment of the integrity of the grafts, and damage to
      the filaments. The fenestrations were more likely to extend in the woven fabrics,
      whereas the knitted fabrics were more resistant to fraying. The use of the
      electric cautery demonstrated the ability to create a fenestration by
      simultaneously perforating/cutting and edge sealing. Any safe fenestration
      requires a perforating method that ensures the sealing of the edge of the graft
      material with a well-controlled diameter. A preoperative fenestration can be
      tolerated, but there are risks of damage to the stent grafts when reloading the
      device. More elegant methods of preoperative fenestration, particularly in situ
      retrograde laser fenestration, are in development and deserve clinical
      validation.

PMID- 22150359
TI  - Modeling intelligent adversaries for terrorism risk assessment: some necessary
      conditions for adversary models.
AB  - Intelligent adversary modeling has become increasingly important for risk
      analysis, and a number of different approaches have been proposed for
      incorporating intelligent adversaries in risk analysis models. However, these
      approaches are based on a range of often-implicit assumptions about the desirable
      properties of intelligent adversary models. This "Perspective" paper aims to
      further risk analysis for situations involving intelligent adversaries by
      fostering a discussion of the desirable properties for these models. A set of
      four basic necessary conditions for intelligent adversary models is proposed and
      discussed. These are: (1) behavioral accuracy to the degree possible, (2)
      computational tractability to support decision making, (3) explicit consideration
      of uncertainty, and (4) ability to gain confidence in the model. It is hoped that
      these suggested necessary conditions foster discussion about the goals and
      assumptions underlying intelligent adversary modeling in risk analysis.

PMID- 22150360
TI  - Juvenile stress potentiates aversive 22-kHz ultrasonic vocalizations and freezing
      during auditory fear conditioning in adult male rats.
AB  - Traumatic experiences that occur during adolescence can render individuals
      vulnerable to mood and anxiety disorders. A model in juvenile rats (age: 27-29
      days) was developed previously to study the long-term effects of adolescent
      stress exposure on behaviour and physiology. This paradigm, termed juvenile
      stress, involves subjecting juvenile rats to different stressors on consecutive
      days over a 3-day period. Here, we investigated the effects of the juvenile
      stress paradigm on freezing behaviour and aversive 22-kHz ultrasonic
      vocalizations (USVs) during auditory fear conditioning in adult male rats (age:
      68-90 days). We found that rats previously subjected to juvenile stress increased
      aversive 22-kHz USVs (total calls and time spent calling) compared with controls
      during fear-conditioning training. The acoustic USV parameters between control
      and juvenile stress rats were largely equivalent, including duration, peak
      frequency and amplitude. While rats did not differ in freezing behaviour during
      fear conditioning, juvenile stress rats exhibited greater cue-conditioned
      freezing upon testing 24 h later. Our results show that juvenile stress elicited
      different long-term changes in freezing and aversive USVs during fear
      conditioning. Furthermore, they highlight the importance of assessing USVs to
      detect experience-dependent differences between control and stress-exposed
      animals which are not detectable by measuring visible behaviour.

PMID- 22150361
TI  - A case of semantic variant primary progressive aphasia with severe insular
      atrophy.
AB  - Insular degeneration has been linked to symptoms of frontotemporal dementia
      (FTD). Presented in this case is a patient exhibiting semantic variant primary
      progressive aphasia, behavioral disturbance. Upon autopsy, he was found to have
      severe insular atrophy. In addition, selective serotonin reuptake inhibitors were
      ineffective in reducing symptoms of obsessive-compulsive behaviors or emotional
      blunting. This case suggests that  Seeley et al.'s (2007 , Alzheimer Disease &
      Associated Disorders, 21, S50) hypothesis that von Economo neurons and fork cell
      rich brain regions, particularly in the insula, are targeted in additional
      subtypes of FTD beyond the behavioral variant.

PMID- 22150362
TI  - Wells' syndrome associated with parvovirus in a 5-year old boy.
AB  - Wells' syndrome, otherwise known as eosinophilic cellulitis, is a rare dermatosis
      seen more commonly in adults than in children. In this article, we present a 5
      year-old Caucasian boy who initially presented with pruritic, erythematous
      macules and papules evolving to bullae formation. Subsequent histology confirmed
      diagnosis of Wells' syndrome, and additional blood work also demonstrated
      positive immunoglobulin (Ig)M and IgG for parvovirus. In many instances, the
      direct etiology of Wells' syndrome is unclear, but the link between parvoviral
      infection and development of Wells' syndrome could further support an additional
      cause.

PMID- 22150363
TI  - Reprogramming of pancreatic exocrine cells towards a beta (beta) cell character
      using Pdx1, Ngn3 and MafA.
AB  - Pdx1 (pancreatic and duodenal homeobox 1), Ngn3 (neurogenin 3) and MafA (v-maf
      musculoaponeurotic fibrosarcoma oncogene family, protein A) have been reported to
      bring about the transdifferentiation of pancreatic exocrine cells to beta (beta)
      cells in vivo. We have investigated the mechanism of this process using a
      standard in vitro model of pancreatic exocrine cells, the rat AR42j-B13 cell
      line. We constructed a new adenoviral vector encoding all three genes, called Ad
      PNM (adenoviral Pdx1, Ngn3, MafA construct). When introduced into AR42j-B13
      cells, Ad-PNM caused a rapid change to a flattened morphology and a cessation of
      cell division. The expression of exocrine markers is suppressed. Both insulin
      genes are up-regulated as well as a number of transcription factors normally
      characteristic of beta cells. At the chromatin level, histone tail modifications
      of the Pdx1, Ins1 (insulin 1) and Ins2 (insulin 2) gene promoters are shifted in
      a direction associated with gene activity, and the level of DNA CpG methylation
      is reduced at the Ins1 promoter. The transformed cells secrete insulin and are
      capable of relieving diabetes in streptozotocin-treated NOD-SCID (non-obese
      diabetic severe combined immunodeficiency) mice. However the transformation is
      not complete. The cells lack expression of several genes important for beta cell
      function and they do not show glucose-sensitive insulin secretion. We conclude
      that, for this exocrine cell model, although the transformation is dramatic, the
      reprogramming is not complete and lacks critical aspects of the beta cell
      phenotype.

PMID- 22150364
TI  - The importance of addressing heteroscedasticity in the reliability analysis of
      ratio-scaled variables: an example based on walking energy-cost measurements.
AB  - AIM: When analysing the reliability of ratio-scaled variables, such as walking
      energy cost, variability of the error term often increases with increasing mean
      values. This phenomenon is called heteroscedasticity, and it makes the analysis
      of reliability more complicated. This study presents an examination of
      heteroscedasticity for walking energy cost before analysing the reliability.
      METHOD: Walking energy cost was collected from 33 children with cerebral palsy
      (CP), with varying Gross Motor Function Classification System (GMFCS) levels (19
      males; 14 females; mean age: 7y 6mo [SD 2y 6mo]; GMFCS levels I [n=16], II [n=7],
      and III [n=10]). It was assessed by measuring oxygen uptake during 10 minutes of
      resting and 5 minutes of walking at comfortable speed. Measurements were
      performed twice, within 4 to 6 weeks. Primary outcomes included gross energy
      cost, gross non-dimensional energy cost, net energy cost, net non-dimensional
      energy cost, speed, and non-dimensional speed. Heteroscedasticity was analysed
      with Bland-Altman plots and Kendall's tau. RESULTS: Visual inspection of the
      Bland-Altman plots showed heteroscedasticity for gross energy cost, gross non
      energy cost, and net energy cost. This was confirmed by Kendall's tau
      coefficients. Accordingly, data were logarithmically transformed, and reliability
      was assessed with ratio statistics. For speed, heteroscedasticity was not
      observed. INTERPRETATION: Variability of gross energy cost, gross non-energy
      cost, and net energy cost, assessed across different GMFCS levels in children
      with CP, was proportional to the mean, indicating the presence of
      heteroscedasticity. This finding emphasizes the importance of always performing a
      heteroscedasticity examination in reliability studies on energy cost and
      reporting the reliability statistics accordingly.

PMID- 22150365
TI  - Cellular therapy for cancer: let there be light.

PMID- 22150366
TI  - Genetic engineering of T cells for the immunotherapy of haematological
      malignancies.
AB  - Accumulating experimental and clinical evidence has been obtained over recent
      years in support of the notion that the immune system has the potential to cure
      cancer. The most convincing example is the graft versus leukaemia effect observed
      after allogeneic haematopoietic stem cell transplantation. In the autologous
      setting, however, the isolation and expansion of naturally occurring tumour
      specific T cells is a challenging task. Cancer antigens are often self-antigens
      and cancer-specific T cells are thus subject to selective mechanisms of central
      and peripheral tolerance. The significant advances in gene-transfer technologies
      developed over the last decade have offered new tools to overcome these
      limitations. Natural T cells can be genetically modified to generate high numbers
      of 'supernatural' tumour-reactive T cells from virtually every cancer patient.
      Supernatural T cells may express clonal receptors providing new specificities,
      factors increasing T-cell performance or safety factors enabling their
      elimination in case of toxicity. Technological improvements applied to novel
      concepts of T-cell biology and oncogenesis will allow to simultaneously equip T
      cells with different transgenes and expand a real 'army' of lymphocytes trained
      to selectively eradicate cancer cells.

PMID- 22150367
TI  - Genetic variation in the Toll-like receptor gene cluster (TLR10-TLR1-TLR6)
      influences disease course in sarcoidosis.
AB  - Sarcoidosis is an inflammatory disease of unknown etiology. Various
      microorganisms have been proposed as etiologic agent suggesting a role for
      pattern-recognition receptors such as Toll-like receptors (TLRs) in disease
      pathogenesis, with a special interest in TLR-2. TLR-10, TLR-1, and TLR-6 act as
      co-receptors for TLR-2 and the genes encoding these receptors are located in a
      gene cluster on chromosome 4. The aim of our study was to assess differences in
      genetic variation in the TLR10-TLR1-TLR6 gene cluster between patients and
      controls. A total of eight single nucleotide polymorphisms were genotyped in 447
      healthy controls and 533 patients, divided in 425 with sarcoidosis and 108 with
      Lofgren's syndrome. Comparison of the total patient cohort with controls showed
      that the allele frequencies of rs1109695, rs7658893 (TLR-10), and rs5743604 as
      well as rs5743594 (TLR-1) differed significantly. Haplotype analysis showed that
      the most common haplotype found was significantly decreased in patients with
      chronic sarcoidosis. Furthermore, a less common haplotype was found to be
      significantly increased in patients with Lofgren's syndrome as well as
      sarcoidosis patients with self-remitting disease, indicating that it could act as
      a disease modifying haplotype. In conclusion, our study suggests that absence of
      the common haplotype in the TLR10-TLR1-TLR6 gene cluster increases the risk of
      developing chronic disease in patients already affected by sarcoidosis. Based on
      their role as co-receptors for TLR-2, this study supports the growing evidence
      that aberrant TLR-2 function is important in sarcoidosis disease pathogenesis.

PMID- 22150368
TI  - The dynamic expression of allograft inflammatory factor-1 in hepatic tissues and
      splenic cells of BALB/c mice with Schistosoma japonicum infection.
AB  - Allograft inflammatory factor-1 (AIF-1) was originally cloned from a rat heart
      allograft under chronic rejection. Data from many studies suggested an important
      role of AIF-1 in several inflammatory processes. The aim of this study was to
      examine the dynamic expression of AIF-1 and its association with the pathogenesis
      of hepatic schistosomiasis in BALB/c mice infected with S. japonicum. The
      expression of AIF-1 and tumour necrosis factor-alpha (TNF-alpha) was determined
      by enzyme-linked immunosorbent assay, western blot and immunohistochemistry. AIF
      1 and TNF-alpha were overexpressed in hepatic tissues at the early stage of
      infection, and then diminished with the length of infection. On culturing
      splenocytes stimulated by soluble egg antigen for 72 h, the expression of AIF-1
      in infected mice was suppressed, but TNF-alpha increased gradually. Our results
      showed that AIF-1 was overexpressed in the liver of BALB/c mice infected with S.
      japonicum, and the interaction between AIF-1 and TNF-alpha or other cytokines
      played an important role in the pathogenesis and progression of hepatic
      schistosomiasis.

PMID- 22150369
TI  - Frequencies of 10 autosomal minor histocompatibility antigens in Korean
      population and estimated disparities in unrelated hematopoietic stem cell
      transplantation.
AB  - Disparity of minor histocompatibility antigens (mHAs) is known to induce graft
      versus-tumor and graft-versus-host disease reactions in stem cell
      transplantation. Not much information is available on genotypic and phenotypic
      distributions of the currently identified mHAs, especially in Korean population.
      Therefore, we report genotype and phenotype frequency analyses of 10 autosomal
      mHAs in 329 unrelated healthy Koreans using the Sequenom MassARRAY matrix
      assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry
      (MS) system and polymerase chain reaction-sequence specific primers (PCR-SSP).
      Estimates of the probability of immunogenic mismatches between donor/recipient
      pairs were made from observed phenotypic frequencies. HA-1 was the most favorable
      mHA for clinical application with the highest disparity of 7.0%. Similar results
      were obtained in ACC-1. The Korean population can benefit the most in a setting
      of matched major histocompatibility complex (MHC)-restricted mHAs-mismatched
      unrelated hematopoietic stem cell transplantations with the disparity rate of
      27.5% with eight hematopoietic mHAs. This is the first comprehensive report on
      the genotypic and phenotypic frequency distributions of human mHAs in the Korean
      population. It can contribute to not only donor selection before transplantation
      but also therapeutic approaches after transplantation. It is expected that mHA
      based immunotherapy will lead to a new treatment modality tailored for patients
      at high risk of relapse following allogeneic hematopoietic cell transplantation.

PMID- 22150370
TI  - Identification of three MICA alleles in the genotype of a patient with chronic
      lymphocytic leukemia.
AB  - Major histocompatibility complex (MHC) class I-related chain A gene (MICA)
      sequence-based genotyping (SBT) was attempted on a peripheral blood sample
      collected from a patient evaluated for hematopoietic stem cell retransplant. The
      electropherogram pattern of MICA SBT indicated the possibility of carrying more
      than two MICA alleles. Subsequent cloning and sequencing of the polymerase chain
      reaction products revealed the presence of three distinct MICA alleles:
      MICA*008:01/:04 (A5.1), MICA*007:01(A4), and MICA*002:01 (A9) in the genotype of
      this patient. The origin of the third extra MICA allele could not be determined
      and would require MICA genotyping information from other family members, which is
      unavailable.

PMID- 22150371
TI  - Prognostic role of high-sensitivity C-reactive protein and B-type natriuretic
      peptide in implantable cardioverter-defibrillator patients.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) and B-type natriuretic
      peptide (BNP) are useful biomarkers for cardiovascular risk stratification.
      Little data are available regarding the prognostic value of hs-CRP and BNP serum
      levels and future ventricular arrhythmic events triggering implantable
      cardioverter defibrillator (ICD) therapy. METHODS: A total of 100 patients
      eligible for ICD implantation were enrolled in a prospective cohort study. Serum
      levels of hs-CRP and BNP were obtained the day before ICD implantation and at
      scheduled follow-up visits. For risk analysis, the study cohort was dichotomized
      based on serum level of hs-CRP using a cut-off value of 3 mg/L. The endpoint was
      appropriate ICD therapy triggered by ventricular arrhythmias during a follow-up
      of 24 months. RESULTS: Appropriate ICD therapy was delivered in 20% of patients.
      Median baseline serum level of hs-CRP was significantly higher in patients with
      appropriate ICD therapy than in those without appropriate ICD therapy (5.33 mg/L
      vs 2.19 mg/L; P = 0.002). The same was true for median serum levels of hs-CRP and
      BNP during follow-up (5.43 mg/L vs 2.61 mg/L, P = 0.001 and 261.0 pg/mL vs 80.1
      pg/mL, P = 0.01, respectively). Multivariate analysis demonstrated that baseline
      hs-CRP level > 3 mg/L was independently associated with appropriate ICD therapy
      (odds ratio 4.0, 95% 1.1-14.2; P = 0.03). CONCLUSION: Elevated preimplantation hs
      CRP serum level is independently associated with increased risk for appropriate
      ICD therapy. Monitoring for elevated BNP levels during follow-up adds to the
      assessment of risk for future arrhythmias.

PMID- 22150373
TI  - Miliaria rubra and thrombocytosis in pseudohypoaldosteronism: case report.
AB  - Pseudohypoaldosteronism type 1 (PHA1) is a disease involving a state of renal
      tubular unresponsiveness to the action of aldosterone and characterized by
      excessive salt loss in the urine, hyperkalemia, and metabolic acidosis. In
      kidney, PHA1 may occur primarily by mutations in the subunits of the sodium
      channel or in the mineralocorticoid receptors, and secondarily by several renal
      disorders. Miliaria rubra and thrombocytosis are reported in a 6-month-old girl
      with PHA1. In patients with PHA1, miliaria rubra-like cutaneous eruptions are
      suggested to occur due to obstruction of eccrine sweat glands through
      inflammation caused by excessive sodium excretion in sweat during hyponatremic
      crises. The presence of thrombocytosis in patients with PHA1 has not been
      previously reported. A hypothesis is proposed suggesting that sympathetic
      activation which provides vascular tonus during sodium excretion in sweat and
      salt-depletion crisis may play a role in the development of eruptions and
      thrombocytosis in patients with PHA1.

PMID- 22150375
TI  - Low-density platelet populations demonstrate low in vivo activity in sporadic
      Alzheimer disease.
AB  - Platelets contain a substantial quantity of amyloid-precursor protein (APP) and
      beta-amyloid. However, despite the large importance of APP and beta-amyloid to
      dementia, little is known about platelets in sporadic Alzheimer dementia (AD).
      Furthermore, platelet heterogeneity influences human pathology and has been
      described to affect the progression of AD. This study investigated AD platelets
      with respect to density diversity and in vivo activity associated with density
      sub-fractions. We included 39 AD patients and used, as controls, 22 elderly
      individuals without apparent memory disorder. A continuous PercollTM gradient
      covering the density span 1.04-1.09 kg/l provided the basis to divide platelets
      of whole blood into density fractions (n = 16). All platelet populations were
      evaluated accordingly. Platelet counts were determined electronically. A flow
      cytometer was put to use to measure surface-bound fibrinogen as a measure of
      platelet in vivo activity. Samples obtained from patients diagnosed with sporadic
      AD contained platelets (fractions numbers 4-16) that circulated with
      significantly less surface-bound fibrinogen, i.e., their platelet activation in
      vivo was reduced, compared with controls. In particular, highly significant
      differences (p < 0.001) were obtained for the six less dense platelet populations
      (fractions numbers 11-16) when comparing sporadic AD with controls. In contrast,
      the densest AD platelets in fractions numbers 1-3 did not differ significantly
      from control cells with respect to in vivo platelet-bound fibrinogen. It is
      concluded that sporadic AD is characterized by lower density platelet populations
      that, while circulating, exhibited reduced activation. The clinical significance
      of this finding is unclear but these results suggest the importance of platelet
      heterogeneity in dementia as a topic for further investigation.

PMID- 22150374
TI  - Platelet reactivity in type 2 diabetes mellitus: a comparative analysis with
      survivors of myocardial infarction and the role of glycaemic control.
AB  - Patients with type 2 diabetes mellitus exhibit considerable platelet dysfunction,
      though this is poorly characterized in patients with diabetes taking aspirin for
      the primary prevention of cardiovascular events. We sought to compare platelet
      function in this patient population with that of a high-risk group of non
      diabetic subjects with a history of previous myocardial infarction (MI), and to
      assess whether glycaemic control impacts on platelet function. METHODS: Platelet
      aggregation was measured in response to incremental concentrations of five
      platelet agonists using light transmission aggregometry. All patients were taking
      aspirin, and aspirin insensitivity was defined as >= 20% arachidonic acid (AA)
      mediated aggregation. Patients with diabetes were divided according to glycaemic
      control (HbA(1c)): optimal <= 6.5, good 6.6-7.4 and suboptimal >= 7.5%. RESULTS:
      In total, 85 patients with type 2 diabetes and 35 non-diabetic patients with
      previous MI were recruited. Compared to MI patients, diabetes patients had
      increased aggregation in response to multiple concentrations of epinephrine,
      collagen, adenosine diphosphate and AA. Aspirin insensitivity was more common in
      type 2 diabetes (15% vs. 0%, p=0.037). Platelet aggregation was increased in
      response to several agonists patients with suboptimal glycaemic control compared
      to patients with optimal control. Aspirin insensitivity was also more common in
      patients with suboptimal glycaemic control compared to those with good or optimal
      control (26.0% vs. 8.3% vs. 4%, p=0.04). CONCLUSION: Patients with type 2
      diabetes mellitus, without proven vascular disease, exhibit platelet dysfunction
      and have increased platelet aggregation and aspirin insensitivity compared to non
      diabetic patients with previous MI. Platelet dysfunction in diabetes is more
      severe in patients with suboptimal glycaemic control.

PMID- 22150376
TI  - Boat race: rhythm and the possibility of collective performance.
AB  - Many sociologists have observed the close connection between coordination and
      rhythm. In order to accomplish a communal task, participants need to develop a
      common rhythm if they are to coordinate their actions. Indeed, the harder the
      collective task, the more critical - but difficult - it is for participants to
      develop a common rhythm in order to synchronize their actions. Rhythm is thus an
      important and recurrent feature of social performance. This article explores the
      ways in which participants try to generate common rhythm in order to execute
      collective performances. To this end, the paper takes a single sporting example.
      It examines a decisive period in the 153rd Oxford and Cambridge Boat Race in 2007
      to examine how a small social group, the Cambridge crew, struggled to create and
      maintain a rhythm in order to maximize their rowing performance.

PMID- 22150377
TI  - Genocide as a matter of degree.
AB  - This article employs Max Weber's ideal-type method to classify genocides based on
      their degree of mass killing, unilateralism, and ethnic liability. The
      identification of the elements of genocide draws from a general theory of
      genocide (Campbell 2009, 2010) and from theories of social control employing
      Donald Black's (1995, 1998) theoretical approach, known as pure sociology.
      Because these theories identify the social features associated with each element
      of genocide, they can explain the form genocides take.

PMID- 22150378
TI  - Cosmopolitan communication online: YouTube responses to the anti-Islam film
      Fitna.
AB  - In 2008, a Dutch member of parliament released a short anti-Islamic film entitled
      Fitna, which stirred a huge public controversy and provoked public condemnations
      around the world. In response to the film, hundreds of videos were uploaded on
      YouTube, mostly with the aim to provide a more positive representation of Islam,
      express support for the author and his views, or defend his freedom of speech.
      Drawing on interviews with YouTube users who posted the videos, this paper
      reflects on the capacity of the Internet to sustain cosmopolitan communication
      and examines how cosmopolitan attitudes and practices on-line differ depending on
      the participants' cultural and social background, especially their religious
      affiliations. Particular attention is paid to how the opportunities for
      cosmopolitan communication are shaped by the unequal distribution of cosmopolitan
      attitudes and practices among groups, and by global inequalities of power. In
      addressing these issues, the paper also engages with broader debates about
      cosmopolitanism, and argues for an understanding of cosmopolitanism as a quest
      for universalism, which remains anchored in the particular, but involves
      communication across difference, and requires openness to the possibility that
      the other is right.

PMID- 22150379
TI  - Cultural diversity, democracy and the prospects of cosmopolitanism: a theory of
      cultural encounters.
AB  - The most appropriate way of theorizing cultural diversity is to situate it in the
      context of a broader relational theory of culture in which the key dynamic is
      cultural encounters. The relational conception of culture places the emphasis on
      the relations between social actors and the processes by which some of these
      relations generate enduring cultural regularities and forms. This has important
      implications for political community and in particular for cosmopolitanism. It is
      in relationships that cultural phenomena are generated and become the basis of
      different kinds of political community. The paper outlines a typology of six
      kinds of cultural encounters and discusses four major cultural trends that
      variously emerge from these encounters. This approach with its emphasis on
      cultural encounters is the broad sociological context in which questions about
      cultural change and the prospects of cosmopolitanism should be discussed.

PMID- 22150380
TI  - Interdisciplinarity and the social sciences: capital, institutions and autonomy.
AB  - Recent discussions about disciplinarity and interdisciplinarity in the social
      sciences have tended to map and critique methods, theories and approaches to
      knowledge production, but spend less time exploring the ways in which
      institutional constraints and personal trajectories produce different kinds of
      disciplinarity and interdisciplinarity. In this paper we present findings on
      interdisciplinarity from UK research undertaken as part of an EC project on
      knowledge, gender and institutions. The research involved a small survey (n =
      14), in-depth interviews (n = 5), two focus groups (n = 7) and observation of
      social scientists in one university department between June 2006 and April 2007.
      We reflect on the unwillingness of social scientists to confront the conditions
      of our academic labour in an account of our difficulties with gaining access and
      respondents in this study, before moving on to consider some of the different
      ways in which interdisciplinarity and disciplinary commitments were related to
      particular forms of scientific and symbolic capital. We go on to discuss this in
      relation to the autonomy of academic teaching-and-research staff compared to
      contract researchers, and consider the implications of our findings for the
      future of interdisciplinarity and the social sciences.

PMID- 22150381
TI  - Ilya Neustadt, Norbert Elias, and the Leicester Department: personal
      correspondence and the history of sociology in Britain.
AB  - The central aims of this paper are: (1) to explore the utility of using personal
      correspondence as a source of data for sociological investigations into the
      history of sociology in the UK; (2) in relation to this undertaking, to advance
      the beginnings of a figurational analysis of epistolary forms; and (3), to
      provide an empirically-grounded discussion of the historical significance of the
      Department of Sociology at the University of Leicester (a University largely
      ignored in 'standard histories' of the subject) at a formative phase in the
      development of the discipline within the UK. The correspondence drawn upon in the
      paper is between Norbert Elias and Ilya Neustadt between 1962 and 1964 when Elias
      was Professor of Sociology at the University of Ghana and Ilya Neustadt was
      Professor of Sociology and Head of the Sociology Department at the University of
      Leicester. From an analysis of this correspondence, we elucidate an emergent
      dynamic to the relationship between Neustadt and Elias, one which, we argue,
      undergirds the development of sociology at Leicester and the distinctive
      character of the intellectual climate that prevailed there during the 1960s. The
      paper concludes with a consideration of whether it was a collapse of this dynamic
      that led to a total breakdown in the relationship between Neustadt and Elias, and
      by extension, an important phase in the expansion of sociology at Leicester.

PMID- 22150382
TI  - Culinary culture and globalization: an analysis of British and German Michelin
      starred restaurants.
AB  - The high-end restaurant segment in Britain and Germany has long been shaped by
      the cultural hegemony of French haute cuisine, perpetuated by multiple processes,
      including the influence of the Michelin or Red Guide. Traditionally, this
      hegemony has been expressed in the prevalence of French expatriate chefs,
      culinary techniques and style and even restaurant culture. This paper
      investigates whether processes of globalization have weakened or even undermined
      this French cultural dominance in fine-dining restaurants and their culinary
      culture. To this end, the study identifies the various forms taken by
      globalization processes in this industry segment and then assesses their impact
      on the dominance of the French paradigm of culinary culture. The investigation
      focuses on British and German Michelin-starred restaurants, underlining both
      commonalities and divergences in the process of interaction between French,
      global and local influences. The study employs a qualitative method, using a
      number of case studies to discern cross-industry patterns. All chefs with two or
      three stars in the two countries, i.e. 45 chefs, were selected for the analysis
      of their cuisine.

PMID- 22150383
TI  - The gift in interaction: a study of 'picking-up the bill'.
AB  - This paper analyses the phenomenon of 'picking up the bill', thereby contributing
      to a resurgence of sociological interest in gift exchange. Drawing on
      ethnomethodology, it describes and locates a distinctive theoretical approach.
      Utilizing video recordings, the analysis considers the interactional constitution
      of gifts and how gift exchange is locally invoked via the norm of reciprocity.
      Recurrent practices are described, through which gifts are brought into being,
      with reciprocity invoked, by benefactor and beneficiary alike, to manage social
      problems of acceptance, rather than to sanction insufficient contributions. The
      study describes the social character of what are perhaps the preeminent gifts
      exchanged in modern societies; where one person pays for another's consumption.

PMID- 22150385
TI  - Dementia and relationships: experiences of partners in minority ethnic
      communities.
AB  - AIM: This article is a report of a study aimed at examining the experiences of
      partners of people with dementia in two minority ethnic communities. BACKGROUND:
      Cultural background is important in how people perceive the effects of dementia
      and respond to them. To date there has been little research on the experiences of
      minority ethnic partners in the U.K. METHOD: Using a constructivist grounded
      theory approach data collection took place in London, England, over an 18-month
      period between 2007 and 2009. A total of 43 in-depth interviews were conducted
      with seven Greek Cypriot and six African Caribbean partners of people with
      dementia. FINDINGS: The outcomes of the study revealed partners of people with
      dementia engaged in an ongoing process of 'redefining relationships'. Greek
      Cypriot partners tended to emphasize family relationships whilst African
      Caribbean partners tended to view themselves primarily as an individual or as
      part of a couple. CONCLUSION: Increased understanding of how dementia is
      experienced by partners of people from specific ethnic groups with dementia can
      equip nurses to give culturally appropriate advice and support. The study
      findings suggest that ethnicity alone cannot account for individual responses to
      dementia in a partner, and therefore awareness of cultural factors needs to be
      balanced with sensitivity to the unique life experience and relationships of the
      individuals.

PMID- 22150386
TI  - Exposure of neonatal rats to anti-androgens induces penile mal-developments and
      infertility comparable to those induced by oestrogens.
AB  - We previously reported that oestrogen exposure in neonatal rats induced permanent
      infertility and malformed penis characterized by fat accumulation, which replaced
      most of the smooth muscle cells and cavernous spaces in the body of the penis,
      structures essential for erection. The objective of this study was to determine
      if reduced androgen production/action in the neonatal period, in the absence of
      exogenous oestrogen exposure, induces penile deformities similar to those caused
      by oestrogen. Male rats were treated from postnatal days 1-6 with GnRH antagonist
      antide (A, 10 mg/kg) or androgen receptor (AR) antagonist flutamide (F, 50 mg/kg)
      or F + A, with or without AR agonist dihydrotestosterone (DHT, 20 mg/kg). For
      comparison, pups received diethylstilbestrol (DES, 0.1 mg/kg), with or without
      DHT. Tissues were collected at ages 7 and 12 days and at adulthood. Flutamide
      alone decreased penile length and weight significantly (p < 0.05), but it caused
      neither fat accumulation, nor affected fertility (80% vs. 87% in controls).
      Antide alone reduced penile length and weight significantly, and induced fat
      accumulation in 4/11 rats and infertility in 13/14 rats. Conversely, all 11 F + A
      treated rats, similar to all nine DES-treated rats, had fat accumulation and loss
      of smooth muscle cells and cavernous spaces in the body of the penis and were
      infertile. In addition, reductions in penile length and weight were higher than
      in rats treated with F or A alone. DHT co-administration mitigated penile
      deformities in the DES group, but did not in the F + A group. Testicular
      testosterone was reduced by 70-95% at 7 or 12 days of age in all treated groups,
      except in the F group, which had threefold higher testosterone than controls.
      Collectively, data unequivocally show that reduced androgen production/action in
      the neonatal period, in the absence of oestrogen exposure, induces permanent
      infertility and malformed penis similar to that caused by oestrogen.

PMID- 22150387
TI  - Prediction of adult height in girls: the Beunen-Malina-Freitas method.
AB  - The purpose of this study was to validate and cross-validate the Beunen-Malina
      Freitas method for non-invasive prediction of adult height in girls. A sample of
      420 girls aged 10-15 years from the Madeira Growth Study were measured at yearly
      intervals and then 8 years later. Anthropometric dimensions (lengths, breadths,
      circumferences, and skinfolds) were measured; skeletal age was assessed using the
      Tanner-Whitehouse 3 method and menarcheal status (present or absent) was
      recorded. Adult height was measured and predicted using stepwise, forward, and
      maximum R (2) regression techniques. Multiple correlations, mean differences,
      standard errors of prediction, and error boundaries were calculated. A sample of
      the Leuven Longitudinal Twin Study was used to cross-validate the regressions.
      Age-specific coefficients of determination (R (2)) between predicted and measured
      adult height varied between 0.57 and 0.96, while standard errors of prediction
      varied between 1.1 and 3.9 cm. The cross-validation confirmed the validity of the
      Beunen-Malina-Freitas method in girls aged 12-15 years, but at lower ages the
      cross-validation was less consistent. We conclude that the Beunen-Malina-Freitas
      method is valid for the prediction of adult height in girls aged 12-15 years. It
      is applicable to European populations or populations of European ancestry.

PMID- 22150388
TI  - A tribute to professor Dr. Emeritus Gaston Beunen.

PMID- 22150390
TI  - Effects of wilting and molasses addition on fermentation and bacterial community
      in guinea grass silage.
AB  - AIMS: Acetic acid is considered an important preservative in tropical grass
      ensiling. The objective of the current experiments was to follow the ensiling
      fermentation of low dry matter (DM) tropical grass as a model to study changes in
      bacterial communities during acetic acid fermentation. METHODS AND RESULTS:
      Direct-cut and wilted guinea grass silage was prepared with and without molasses.
      A high acetic acid level was observed during the fermentation of direct-cut
      silage, and long storage increased the butyric acid and ethanol content if
      molasses was not added. The lactic acid production in wilted silage was greater
      than the acetic acid production, but prolonged ensiling decreased the lactic to
      acetic acid ratio regardless of molasses addition. Adding molasses enhanced the
      lactic acid content in both direct-cut and wilted silage. The bacterial
      community, identified by denaturing gradient gel electrophoresis, was affected by
      wilting and molasses addition. Bands for Pantoea sp. and Morganella sp. became
      faint when acetic acid fermentation was suppressed, and those for Pediococcus
      pentosaceus and Lactococcus garvieae were detected when lactic acid fermentation
      was enhanced by wilting and molasses addition. Lactobacillus plantarum and
      Lactococcus lactis were found throughout the ensiling process in all silage
      types. CONCLUSION: Distinct changes occurred in the bacterial community in guinea
      grass silage because of wilting and molasses addition. These changes could
      explain how lactic acid fermentation was enhanced but could not help determine
      which bacteria were associated with enhanced acetic acid fermentation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The study reveals the effects of wilting
      and molasses during ensiling of low DM tropical grasses and the associated
      bacteria.

PMID- 22150391
TI  - Seroprevalence of Toxoplasma gondii from free-ranging black bears ( Ursus
      americanus ) from Florida.
AB  - Toxoplasma gondii is a significant worldwide parasitic protozoan. In the present
      study, prevalence of antibodies of T. gondii was examined from 29 free-ranging
      black bears ( Ursus americanus ) from south-central Florida where the host
      species was listed as state threatened during this project. Overall T. gondii
      prevalence was found to be 44.8%, specifically 46.2% in male and 43.8% in female
      U. americanus , using a modified agglutination test (1:25 titer). Seroprevalence
      differences between sexes were not significant (P > 0.05). Results of the present
      study add supportive data to the growing body of evidence suggesting that U.
      americanus has one of the highest T. gondii seroprevalences among all known
      intermediate hosts. In addition, our data emphasize the importance of
      understanding parasitic disease dynamics from a conservation perspective.

PMID- 22150392
TI  - Transitions in care: support group for young adults with Type 1 diabetes.
AB  - AIMS: Young adulthood is a challenging period for patients with Type 1 diabetes
      as developmental changes complicate Type 1 diabetes management and gaps in care
      may arise as patients transition from paediatric to adult providers. This period
      has been associated with worsening diabetes outcomes. One approach to aid young
      adults during this transition period could entail professionally led support
      groups to enhance self-motivation and facilitate peer-to-peer interactions. We
      implemented and evaluated a support group for young adults with Type 1 diabetes
      as a pilot project. METHODS: Young adults with Type 1 diabetes (18-30 years)
      participated in monthly, professionally led support groups for 5 months.
      Questionnaires were completed pre- and post-group and chart review data were
      collected regarding glycaemic control and visit frequency in the year before and
      after group participation. RESULTS: Participation in the group was associated
      with improvement in HbA(1c) and decreased self-reported diabetes burden, along
      with a trend for an increase in diabetes-related self-care behaviours. Frequency
      of visits did not vary from pre- to post-group. Discussion topics identified by
      participants included managing diabetes in day-to-day life, experiences and
      interactions with others who do not have diabetes and emotions related to
      diabetes. Participants identified that they sought a diabetes care team that
      offers knowledge, support and a multidisciplinary team. CONCLUSIONS:
      Professionally led support groups may have utility for increasing social support
      and optimizing diabetes outcomes in young adults with Type 1 diabetes.

PMID- 22150394
TI  - Persistent pain and frailty: a case for homeostenosis.
AB  - OBJECTIVES: To compare the association between self-reported moderate to severe
      pain and frailty. DESIGN: Cross-sectional analysis of the Canadian Study of
      Health and Aging Wave 2. SETTING: Community. PARTICIPANTS: Representative sample
      of persons aged 65 and older in Canada. MEASUREMENTS: Pain (exposure) was
      categorized as no or very mild pain versus moderate or greater pain. Frailty
      (outcome) was operationalized as the accumulation of 33 possible self-reported
      health attitudes, illnesses, and functional abilities, subsequently divided into
      tertiles (not frail, prefrail, and frail). Multivariable logistic regression
      assessed for the association between pain and frailty. RESULTS: Of participants
      who reported moderate or greater pain (35.5%, 1,765/4,968), 16.2% were not frail,
      34.1% were prefrail, and 49.8% were frail. For persons with moderate or greater
      pain, the odds of being prefrail rather than not frail were higher by a factor of
      2.52 (95% confidence interval (CI) = 2.13-2.99; P < .001). For persons with
      moderate or greater pain, the odds of being frail rather than not frail were
      higher by a factor of 5.52 (95% CI = 4.49-6.64 P < .001). CONCLUSION: Moderate or
      higher pain was independently associated with frailty. Although causality cannot
      be ascertained in a cross-sectional analysis, interventions to improve pain
      management may help prevent or ameliorate frailty.

PMID- 22150396
TI  - Commentary on: Page M, Taylor J, Blenkin M. Forensic identification science
      evidence since Daubert: Part II--judicial reasoning in decisions to exclude
      forensic identification evidence on grounds of reliability. J Forensic Sci
      2011;56(4):913-7.

PMID- 22150395
TI  - Treatment outcomes of secondarily impetiginized pediatric atopic dermatitis
      lesions and the role of oral antibiotics.
AB  - Patients with atopic dermatitis (AD) are predisposed to infection with
      Staphylococcus aureus, which worsens their skin disease; it has been postulated
      that the lack of antimicrobial peptides due to aberrant allergic inflammation in
      skin with AD could mediate this enhanced bacterial susceptibility. We sought to
      characterize the amounts of S. aureus and biological products found in infected
      AD lesions and whether treatment with topical corticosteroids and oral cephalexin
      as the only antimicrobial improved outcomes. Fifty-nine children with clinically
      and S. aureus-positive impetiginized lesions of AD were enrolled in this study. A
      lesion was graded clinically using the Eczema Area and Severity Index, and wash
      fluid was obtained from the lesion for quantitative bacterial culture and
      antibiotic sensitivities and measurement of bacterial products and cytokines.
      Subjects were re-evaluated 2 weeks after treatment. Improvement in the clinical
      and inflammatory characteristics of impetiginized lesions were noted, even in the
      15% of lesions infected with Methicillin-resistant S. aureus (MRSA). In a
      subgroup of subjects whose lesions did not contain S. aureus 2 weeks after
      initiating treatment, beta-defensin levels were higher at both visits than in
      normal skin. Treatment of uncomplicated impetiginized pediatric AD with topical
      corticosteroids and cephalexin results in significant clinical improvement, even
      in subjects infected with MRSA. We propose that the inhibition of abnormal
      inflammation by the treatment regimen, resulting in the high levels of defensins,
      is involved in the improvement of AD and that systemic antibiotics do not appear
      to be necessary in secondary impetiginized AD.

PMID- 22150397
TI  - Transfer and uptake of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and
      polychlorinated biphenyls (PCBs) into meat and organs of indoor and outdoor
      reared pigs.
AB  - This study was designed to investigate how and to what extent PCDD/Fs and PCBs
      are transmitted from exposure sources to porcine muscle and other tissues derived
      from pigs. The experimental approach involved two longitudinal studies in which
      indoor and outdoor pigs were reared to market readiness using typical animal
      husbandry practices; closely matched samples of soil, feed, bedding, meat, etc.
      were collected and analysed for PCDD/Fs and PCBs. The total PCDD/F + PCB WHO-TEQs
      in pig liver were much higher than in meat and kidney samples from the same
      animals and exceeded the current relevant European Union maximum limits (6 ng
      PCDD/F-TEQ kg-1 fat). Liver samples were also characterised by much lower PCB
      contributions to the total TEQ than for the corresponding meat and kidney
      samples, and by a predominance of many of the hepta- and octa-substituted
      PCDD/Fs. At ages approaching market readiness, TEQ values in meat samples from
      outdoor pigs tended to be slightly higher than those from comparable ages in the
      indoor programme, possibly due to additional intake from soil. Biotransfer
      factors (BTFs) were derived for each of the 39 PCDD/F and PCB congeners measured.
      Interpretation of the findings focused particularly on trends in four selected
      congeners, namely: 2,3,7,8-TCDD, 2,3,4,7,8-PeCDF, PCB 153 and PCB 169. Increases
      in the BTF for PCB 169 in the pig-rearing programmes were noticed when the diet
      changed from being dominated by sow's milk to feed. Much higher transfer factors
      for many of the more heavily chlorinated PCDD/Fs (e.g. 2,3,4,7,8-PeCDF) were
      found in liver compared with meat or kidney samples from the same animals. Soil
      consistently accounted for at least 30% of input for many hexa- or higher
      chlorinated PCDD/Fs, while it rarely representing more than 10% of the total
      intake.

PMID- 22150398
TI  - RCD1-DREB2A interaction in leaf senescence and stress responses in Arabidopsis
      thaliana.
AB  - Transcriptional regulation of gene expression is one major determinant of
      developmental control and stress adaptation in virtually all living organisms. In
      recent years numerous transcription factors controlling various aspects of plant
      life have been identified. The activity of transcription factors needs to be
      regulated to prevent unspecific, prolonged or inappropriate responses. The
      transcription factor DREB2A (DEHYDRATION-RESPONSIVE ELEMENT BINDING 2A) has been
      identified as one of the main regulators of drought and heat responses, and it is
      regulated through protein stability. In the present paper we describe evidence
      that the interaction with RCD1 (RADICAL-INDUCED CELL DEATH 1) contributes to the
      control of DREB2A under a range of conditions. The interaction is mediated by a
      novel protein motif in DREB2A and a splice variant of DREB2A which lacks the
      interaction domain accumulates during heat stress and senescence. In addition
      RCD1 is rapidly degraded during heat stress, thus our results suggest that
      removal of RCD1 protein or the loss of the interaction domain in DREB2A appears
      to be required for proper DREB2A function under stress conditions.

PMID- 22150399
TI  - Ecological responses to UV radiation: interactions between the biological effects
      of UV on plants and on associated organisms.
AB  - Solar ultraviolet (UV)-B radiation (280-315 nm) has a wide range of effects on
      terrestrial ecosystems, yet our understanding of how UV-B influences the complex
      interactions of plants with pest, pathogen and related microorganisms remains
      limited. Here, we report the results of a series of experiments in Lactuca sativa
      which aimed to characterize not only key plant responses to UV radiation in a
      field environment but also consequential effects for plant interactions with a
      sap-feeding insect, two model plant pathogens and phylloplane microorganism
      populations. Three spectrally modifying filters with contrasting UV transmissions
      were used to filter ambient sunlight, and when compared with our UV-inclusive
      filter, L. sativa plants grown in a zero UV-B environment showed significantly
      increased shoot fresh weight, reduced foliar pigment concentrations and
      suppressed population growth of green peach aphid (Myzus persicae). Plants grown
      under a filter which allowed partial transmission of UV-A radiation and
      negligible UV-B transmission showed increased density of leaf surface phylloplane
      microbes compared with the UV-inclusive treatment. Effects of UV treatment on the
      severity of two plant pathogens, Bremia lactucae and Botrytis cinerea, were
      complex as both the UV-inclusive and zero UV-B filters reduced the severity of
      pathogen persistence. These results are discussed with reference to known
      spectral responses of plants, insects and microorganisms, and contrasted with
      established fundamental responses of plants and other organisms to solar UV
      radiation, with particular emphasis on the need for future integration between
      different experimental approaches when investigating the effects of solar UV
      radiation.

PMID- 22150400
TI  - Sympathetic nervous activity, depressive symptoms, and metabolic syndrome in
      black Africans: the sympathetic activity and ambulatory blood pressure in
      Africans study.
AB  - The aim of this study was to examine the association between sympathetic nervous
      activity, depressive symptoms, and metabolic syndrome in a sample of black and
      Caucasian Africans. The sample consisted of healthy men and women: 194 blacks
      (aged, mean +/- SD, 44.1 +/- 7.9 years) and 206 Caucasians (aged, mean +/- SD,
      44.7 +/- 10.8 years). Salivary 3-methoxy-phenylglycol (MHPG) concentration, the
      major metabolite of norepinephrine, was measured during the Stroop mental
      challenge. Depressive symptoms were assessed from the 9-item Patient Health
      Questionnaire. Metabolic syndrome (defined as central obesity plus any other two
      risk factors including raised serum triglycerides, reduced serum high-density
      lipoprotein- cholesterol, raised blood pressure, and raised fasting plasma
      glucose) was prevalent in 43.0% and 36.4% of blacks and Caucasians, respectively.
      In blacks there was, on average, a 16.4% increase in salivary MHPG concentration
      following mental stress, although no significant response was observed in
      Caucasians. The salivary MHPG response in blacks was associated with risk of
      metabolic syndrome (odds ratio [OR] = 1.11, 95% CI, 1.00-1.24) after adjusting
      for age, sex, and baseline salivary MHPG concentration. This association was
      mainly driven by the central obesity component of the metabolic syndrome. The
      salivary MHPG response was also related to moderate-severe depressive symptoms
      (OR = 1.16, 95% CI, 1.04-1.30), and further adjustment for depressive symptoms
      attenuated the association between salivary MHPG response and metabolic syndrome
      (OR = 1.07, 95% CI, 0.96-1.20). These data indicate an association between
      sympathetic activity, depressive symptoms, and metabolic syndrome in a sample of
      black Africans.

PMID- 22150401
TI  - Functions of Abeta, sAPPalpha and sAPPbeta : similarities and differences.
AB  - Amyloid peptide (Abeta) is derived from the cleavage of amyloid precursor protein
      (APP), which also generates the soluble peptide APPbeta (sAPPbeta). An antagonist
      and major APP metabolic pathway involves cleavage by alpha secretase, which
      releases sAPPalpha. Although soluble Abeta oligomers are neurotoxic, Abeta
      monomers share similar properties with sAPPalpha. These include neurotrophic and
      neuroprotective effects, as well as stimulation of neural-progenitor
      proliferation. The properties of Abeta monomers and the neurotrophic capacity of
      sAPPbeta to stimulate axonal outgrowth suggest that Abeta production is not
      deleterious per se. Consequently, therapeutic strategies for Alzheimer's disease
      that are targeted at Abeta-cleaving enzymes should modulate rather than inhibit
      Abeta generation. These strategies should focus on the factors that induce the
      conversion of Abeta monomers into toxic soluble oligomers. Another interesting
      therapeutic approach is to focus on the mechanisms of the different properties of
      sAPPalpha. Indeed, increasing sAPPalpha levels could shift proliferating cells
      towards tumorigenesis. In contrast to its neuroprotective effects, sAPPalpha is
      also able to activate microglia, leading to neurotoxicity. Understanding the
      mechanisms that underlie the different properties of sAPPalpha could therefore
      lead to the development of therapeutic strategies against Alzheimer's disease,
      which could be curative as well as preventive.

PMID- 22150402
TI  - Renbok phenomenon in a patient with alopecia areata universalis and psoriasis.

PMID- 22150403
TI  - Changes in the surface of four calcium silicate-containing endodontic materials
      and an epoxy resin-based sealer after a solubility test.
AB  - AIM: To compare the changes in the surface structure and elemental distribution,
      as well as the percentage of ion release, of four calcium silicate-containing
      endodontic materials with a well-established epoxy resin-based sealer, submitted
      to a solubility test. METHODOLOGY: Solubility of AH Plus, iRoot SP, MTA Fillapex,
      Sealapex and MTA-Angelus (MTA-A) was tested according to ANSI/ADA Specification
      57. The deionized water used in the solubility test was submitted to atomic
      absorption spectrophotometry to determine and quantify Ca(2+), Na(+), K(+),
      Zn(2+), Ni(2+) and Pb(2+) ions release. In addition, the outer and inner surfaces
      of nonsubmitted and submitted samples of each material to the solubility test
      were analysed by means of scanning electron microscopy and energy-dispersive
      spectroscopy (SEM/EDX). Statistical analysis was performed by using one-way anova
      and Tukey's post hoc tests (alpha = 0.05). RESULTS: Solubility results, in
      percentage, sorted in an increasing order were -1.24 +/- 0.19 (MTA-A), 0.28 +/-
      0.08 (AH Plus), 5.65 +/- 0.80 (Sealapex), 14.89 +/- 0.73 (MTA Fillapex) and 20.64
      +/- 1.42 (iRoot SP). AH Plus and MTA-A were statistically similar (P > 0.05), but
      different from the other materials (P < 0.05). High levels of Ca(2+) ion release
      were observed in all groups except AH Plus sealer. MTA-A also had the highest
      release of Na(2+) and K(+) ions. Zn(+2) ion release was observed only with AH
      Plus and Sealapex sealers. After the solubility test, all surfaces had
      morphological changes. The loss of matrix was evident and the filler particles
      were more distinguishable. EDX analysis displayed high levels of calcium and
      carbon at the surface of Sealapex, MTA Fillapex and iRoot SP. CONCLUSIONS: AH
      Plus and MTA-A were in accordance with ANSI/ADA's requirements regarding
      solubility whilst iRoot SP, MTA Fillapex and Sealapex did not fulfil ANSI/ADA's
      protocols. High levels of Ca(2+) ion release were observed in all materials
      except AH Plus. SEM/EDX analysis revealed that all samples had morphological
      changes in both outer and inner surfaces after the solubility test. High levels
      of calcium and carbon were also observed at the surface of all materials except
      AH Plus and MTA-A.

PMID- 22150404
TI  - Variability in muscle activity and wrist motion measurements among workers
      performing non-cyclic work.
AB  - Appropriate sampling strategies for estimation of exposure to physical risk
      factors require knowledge of exposure variability over time. Limited information
      is available about the variability of exposure to physical risk factors for upper
      extremity musculoskeletal disorders, especially during non-cyclic work
      activities. We investigated the magnitude and relative contributions of several
      sources of variance to the total exposure variance among office, custodial, or
      maintenance workers (N = 5 per group). In addition, we examined the homogeneity
      of exposure within each group of workers and exposure contrast between groups of
      workers. Activation of the flexor carpi radialis and upper trapezius muscle
      groups was assessed with surface electromyography (EMG) and wrist motion was
      assessed with electrogoniometry. Exposure information was collected continuously
      over a complete work shift on two occasions. We observed a substantial
      contribution of the within-day-within-subject variance component to the total
      exposure variance for all EMG and electrogoniometer summary measures. We also
      observed limited exposure contrast between the occupational groups in summary
      measures of upper trapezius EMG and most electrogoniometry summary measures. The
      large within-day-within-subject variance suggests the need for prolonged
      measurement durations (e.g., more than 1 hr) in future epidemiologic
      investigations of associations between exposure to physical risk factors and
      upper extremity musculoskeletal disorders.

PMID- 22150405
TI  - Trust, confidence, procedural fairness, outcome fairness, moral conviction, and
      the acceptance of GM field experiments.
AB  - In 2005, Swiss citizens endorsed a moratorium on gene technology, resulting in
      the prohibition of the commercial cultivation of genetically modified crops and
      the growth of genetically modified animals until 2013. However, scientific
      research was not affected by this moratorium, and in 2008, GMO field experiments
      were conducted that allowed us to examine the factors that influence their
      acceptance by the public. In this study, trust and confidence items were analyzed
      using principal component analysis. The analysis revealed the following three
      factors: "economy/health and environment" (value similarity based trust), "trust
      and honesty of industry and scientists" (value similarity based trust), and
      "competence" (confidence). The results of a regression analysis showed that all
      the three factors significantly influenced the acceptance of GM field
      experiments. Furthermore, risk communication scholars have suggested that
      fairness also plays an important role in the acceptance of environmental hazards.
      We, therefore, included measures for outcome fairness and procedural fairness in
      our model. However, the impact of fairness may be moderated by moral conviction.
      That is, fairness may be significant for people for whom GMO is not an important
      issue, but not for people for whom GMO is an important issue. The regression
      analysis showed that, in addition to the trust and confidence factors, moral
      conviction, outcome fairness, and procedural fairness were significant
      predictors. The results suggest that the influence of procedural fairness is even
      stronger for persons having high moral convictions compared with persons having
      low moral convictions.

PMID- 22150406
TI  - Socio-behavioural predictors of young adults' self-reported oral health: 15 years
      of follow-up in the The Norwegian Longitudinal Health Behaviour study.
AB  - OBJECTIVES: Few prospective studies have investigated the impacts of socio
      behavioural position throughout adolescence on self-reported oral health in young
      adulthood. This study aimed to describe the development of oral health behaviours
      between age 15 years (1992) and age 30 years (2007) and to assess how changes in
      or stability of socio-behavioural characteristics during that period influences
      the oral impacts on daily performance (OIDP) and satisfaction with teeth assessed
      at age 30. METHODS: Self-administered questionnaires were included as part of a
      prospective cohort study. In 1992, a representative sample of 963 15-year-old
      adolescents participated in the study; 627 (64%) and 532 (55.2%) remained in the
      study at ages 23 and 30, respectively. A total of 394 (40.9% of baseline sample)
      participated at ages 15, 23 and 30. RESULTS: Cochrane's Q revealed that the
      proportions of individuals who were frequent performers regarding flossing,
      intake of nonsugared mineral water and use of snuff increased whereas the
      proportions who were frequent performers regarding consumption of sugared mineral
      water decreased in subjects with low and high parental education and in both
      sexes across the survey period. Smokers increased in males and decreased in
      females and in subjects with low parental education. Spearman's rank-order
      correlation ranged from 0.19 (nonsugared mineral water) to 0.36 (smoking).
      Multiple logistic regression analysis showed that participants with a stable
      advantaged socio-behavioural position were less likely to report OIDP at age 30.
      Participants with a stable disadvantaged socio-behavioural position were more
      likely to report OIDP at age 30. Participants who were stable satisfied with
      their health and who changed educational status were more likely to be satisfied
      with their teeth at age 30. CONCLUSIONS: Oral health behaviours tracked
      moderately from age 15 to 30. Continuity of an advantaged or disadvantaged socio
      behavioural position across the survey years contributed to differing levels of
      oral health. Early and contemporary public health policies that target
      disadvantaged socio-behavioural groups may help prevent poor oral health
      perceptions in young adults in Norway.

PMID- 22150407
TI  - The functional magnetic resonance imaging-based verbal fluency test in obsessive
      compulsive disorder.
AB  - Clinical use of functional magnetic resonance imaging (fMRI) in obsessive
      compulsive disorder (OCD) is limited by a relative absence of fMRI task
      development, standardization, and normative performance databases. We
      investigated the fMRI-based verbal fluency test (f-VFT) by quantitatively
      evaluating brain activation patterns in OCD participants (8 females and 4 males)
      compared with a normative database (16 females and 16 males). At the group level,
      OCD participants and references had highly similar activation in left-hemisphere
      language regions, including the precentral/premotor cortex, thalamus, basal
      ganglia, and inferior frontal gyrus/frontal operculum. At the interindividual
      level, however, the OCD group had highly variable activation patterns in the
      dorsal and ventral regions of the pre-supplementary motor area (pre-SMA) that may
      correspond with differences in demographic and clinical variables. Further, there
      were significant correlations in the OCD participants between pre-SMA dorsal and
      ventral activation and between dorsal pre-SMA activation and perfectionism. Our
      findings suggest considerable functional anatomical overlap in left-hemisphere
      language regions between OCD participants and references but significantly higher
      pre-SMA interindividual variability in OCD compared to the reference group that
      may be relevant in clinical fMRI application and the theoretical understanding of
      OCD.

PMID- 22150408
TI  - When will we ever learn?

PMID- 22150409
TI  - Early and late parameters describing the offset of neuromuscular blockade are
      highly intercorrelated.
AB  - BACKGROUND: Neuromuscular blocking agents have always shown wide inter-individual
      variability when it comes to their duration of action. This prevents clinicians
      from anticipating the evolution of the neuromuscular block for any given patient.
      With this study, we aimed to assess the nature of the relationships existing
      between different time course parameters used to describe paralysis onset and
      offset. METHODS: Sixty American Society of Anesthesiologists (ASA) score III-IV
      anaesthetised patients were randomised to receive a single equipotent dose
      (2ED95) of either rocuronium, mivacurium or atracurium. We used acceleromyography
      to monitor neuromuscular transmission. We described the relationships between the
      time-interval measurements of: onset, the first response (T1) reappearance, T1
      25% of control, train-of-four ratio 0.25 and 0.75. Pearson correlation
      coefficients were calculated. RESULTS: We found no significant relationships
      between onset and any of the four parameters used to describe the offset. On the
      other hand, we showed strong and highly significant linear relationships between
      all the parameters describing the offset for each of the muscle relaxants studied
      (correlation coefficients ranging from 0.850 to 0.992). CONCLUSIONS: We evidenced
      strong linear correlations between the four offset time course parameters of
      spontaneous recovery after a single neuromuscular blocking agents (NMBAs) bolus.
      Such relationships open up new clinical perspectives concerning quantitative
      neuromuscular transmission monitoring: the scope of individual valuable
      anticipation of the patient's recovery.

PMID- 22150410
TI  - Low dose intrathecal morphine effects on post-hysterectomy pain: a randomized
      placebo-controlled study.
AB  - BACKGROUND: Spinal anesthesia with different doses of intrathecal morphine has
      been shown to relieve post-operative pain. We studied in a prospective
      randomized, double-blind fashion the effects of morphine 0, 100, 200, or 300 MUg
      added to intrathecal bupivacaine on first post-operative 24 h patient-controlled
      analgesia morphine (PCA-morphine) consumption after abdominal hysterectomy under
      general anesthesia. METHODS: One hundred and forty-four American Society of
      Anesthesiologists I-II women were assigned to receive spinal anesthesia with 12
      mg of hyperbaric bupivacaine combined with 100, 200, and 300 MUg morphine or
      saline before standardized general anesthesia was induced. Low transverse
      incision abdominal hysterectomy was performed. Post-operative outcome measures
      were recorded at 1, 2, 4, 6, 12, and 24 h. Primary outcome was 24 h PCA-morphine.
      Secondary outcomes were pain by visual analogue scale (0-10), nausea, pruritus,
      sedation, and respiratory depression. RESULTS: Intrathecal morphine reduced
      accumulated 24 h post-operative morphine consumption. Morphine 100 MUg
      significantly reduced morphine consumption vs. placebo at 0-6 h, 6-12 h, and for
      the entire 0-24 h time interval post-operation. Morphine 200 MUg further
      significantly reduced morphine consumption vs. morphine 100 MUg at 0-6 h and for
      the entire 0-24 h post-operation. There was no further reduction of morphine
      consumption seen with morphine 300 MUg. No serious side effects were seen. Emesis
      was similar in all groups, and pruritus was experienced only in the morphine
      groups. CONCLUSION: Intrathecal morphine supplementation to bupivacaine reduces
      first 24 h PCA-morphine consumption after abdominal hysterectomy under general
      anesthesia, and we found no benefit from increasing the dose over 200 MUg.

PMID- 22150413
TI  - Intracranial calcification in early infantile Krabbe disease: nothing new under
      the sun.
AB  - We report the cases of three children, one male and two females, with a diagnosis
      of early infantile Krabbe disease demonstrating intracranial calcification on
      computed tomography (CT). The pattern of calcification was similar in all
      individuals and involved the internal capsule and cerebral white matter. The
      presence of calcification caused some diagnostic confusion in what was otherwise
      a typical clinical and radiological presentation. This finding is not new and has
      previously been described in publications from the 1980s and 1990s reporting the
      CT and magnetic resonance imaging appearances of Krabbe disease. With increasing
      use of magnetic resonance as the first imaging modality for investigation of
      neurological disorders, characteristic CT appearances may be forgotten. This
      report serves as a reminder that Krabbe disease should be included in the
      differential diagnosis of disorders causing intracranial calcification.

PMID- 22150414
TI  - Platelet-derived microparticles cause CD154-dependent activation of dendritic
      cells.

PMID- 22150415
TI  - Preliminary study on the mineral apposition rate in distal femoral epiphysis of
      New Zealand white rabbit at skeletal maturity.
AB  - Studies investigating the effect of different factors on the skeletal system
      require characterization of an appropriate animal model. Rabbits are among the
      most commonly studied animals for medical research, being used in about 35% of
      musculoskeletal research studies. The present dynamic cross-sectional
      histomorphometric study quantitatively determined mineral apposition rates (MARs)
      in the distal femoral epiphysis in four regions of interest (ROIs) in New Zealand
      white rabbits. ROIs included the craniolateral (CrL), caudolateral (CaL),
      craniomedial (CrM) and caudomedial (CaM) areas, using a reference height at
      different stages of skeletal maturity corresponding to experimental ages of 6, 7
      and 8 months old (M6, M7 and M8). We evaluated whether a correlation exists in
      MARs between the times and the regions examined. Such data could be used in
      studies on growth of the rabbit's femur, on biomaterials for bone integration or
      regeneration and on growth disturbances produced by various pathologic factors.
      We found no interaction at the experimental times; thus, M6, M7 and M8 are
      considered homogeneous in terms of MARs. The velocity profiles of the MARs were
      statistically significantly different among the considered ROIs. For all
      experimental times, the CrM region had a higher MAR than the other ROIs. Both the
      CrM and CaM ROIs had higher MARs than the corresponding lateral ROIs. Our results
      indicate that bone formation is not constant within the cross-section, but is
      statistically different between the ROIs considered.

PMID- 22150416
TI  - Two novel large ANKH deletion mutations in sporadic cases with craniometaphyseal
      dysplasia.

PMID- 22150417
TI  - Mutational spectrum in eight Korean patients with 3-methylcrotonyl-CoA
      carboxylase deficiency.

PMID- 22150418
TI  - Validation of comparative genomic hybridization arrays for the detection of
      genomic rearrangements of the calpain-3 and dysferlin genes.

PMID- 22150419
TI  - Mechanical circulatory support for right heart failure: current technology and
      future outlook.
AB  - The increasing global prevalence of congestive heart failure is a major
      healthcare concern, accounting for a high morbidity rate worldwide. In
      particular, isolated right heart dysfunction after cardiotomy has a poor
      prognosis and is associated with a high mortality rate. The occurrence of
      postoperative right heart failure may develop in more than 40% of patients
      undergoing implantation of a left ventricular assist device (LVAD) and cardiac
      transplantation. To date, mechanical cardiac assistance in the form of VADs has
      become accepted as a therapeutic solution for end-stage patients when a donor
      heart is not available. However, right ventricular (RV) assistance is still in
      the early phase of development when compared with LVAD technology. State-of-the
      art RVADs, both in clinical use and under development, are reviewed in this
      manuscript. Clinical RVADs include the extracorporeal pulsatile Abiomed BVS 5000
      and AB5000, Thoratec PVAD, MEDOS VAD, BerlinHeart Excor, the percutaneous
      continuous flow CentriMag and TandemHeart systems, and the implantable Thoratec
      IVAD. Devices on the horizon, including the wear-free implantable DexAide and the
      minimally invasive Impella RD, are additionally reviewed. In addition to the
      current status of RV assistance, as well as the device categorization, the
      outlook and considerations for successful development of future RVADs were
      discussed.

PMID- 22150421
TI  - Effect of biofilm in irrigation pipes on microbial quality of irrigation water.
AB  - AIMS: The focus of this work was to investigate the contribution of native
      Escherichia coli to the microbial quality of irrigation water and to determine
      the potential for contamination by E. coli associated with heterotrophic biofilms
      in pipe-based irrigation water delivery systems. METHODS AND RESULTS: The
      aluminium pipes in the sprinkler irrigation system were outfitted with coupons
      that were extracted before each of the 2-h long irrigations carried out with
      weekly intervals. Water from the creek water and sprinklers, residual water from
      the previous irrigation and biofilms on the coupons were analysed for E. coli.
      High E. coli concentrations in water remaining in irrigation pipes between
      irrigation events were indicative of E. coli growth. In two of the four
      irrigations, the probability of the sample source, (creek vs sprinkler), being a
      noninfluential factor, was only 0.14, that is, source was an important factor.
      The population of bacteria associated with the biofilm on pipe walls was
      estimated to be larger than that in water in pipes in the first three irrigation
      events and comparable to one in the fourth event. CONCLUSION: Biofilm-associated
      E. coli can affect microbial quality of irrigation water and, therefore, should
      not be neglected when estimating bacterial mass balances for irrigation systems.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This work is the first peer-reviewed report
      on the impact of biofilms on microbial quality of irrigation waters. Flushing of
      the irrigation system may be a useful management practice to decrease the risk of
      microbial contamination of produce. Because microbial water quality can be
      substantially modified while water is transported in an irrigation system, it
      becomes imperative to monitor water quality at fields, rather than just at the
      intake.

PMID- 22150422
TI  - A metacognitive model of the sense of agency over thoughts.
AB  - INTRODUCTION: The sense of agency over thoughts is the experience of oneself qua
      agent of mental action. Those suffering certain psychotic symptoms are thought to
      have a deficient sense of agency. Here I seek to explain this sense of agency in
      terms of metacognition. METHOD: I start with the proposal that the sense of
      agency is elicited by metacognitive monitoring representations that are used in
      the intentional inhibition of thoughts. I apply this model to verbal
      hallucinations and the like and examine the plausibility of this model explaining
      deficits associated with these symptoms. RESULTS: By tying the sense of agency to
      metacognitive inhibition I propose that the loss of a sense of agency in certain
      psychotic symptoms is accompanied by a particular deficit in the patient's
      ability to control their own thinking. This is consistent with the experiences of
      those at high risk of developing hallucinations, who report more intrusive
      thoughts than controls. The model I present is able to explain why those at risk
      of developing verbal hallucinations and those suffering from verbal
      hallucinations have deficits in the intentional inhibition of thought. I defend
      this account from a possible objection by distinguishing the form of the
      intentional inhibition deficit displayed by those suffering verbal hallucination
      from that displayed by those suffering from orbital-frontal cortex lesions and
      posttraumatic stress disorder. CONCLUSION: A plausible hypothesis is that the
      sense of agency over thoughts is elicited by the metacognitive monitoring
      representation used to intentionally inhibit thoughts. The deficit in the sense
      of agency over thoughts associated with certain psychotic symptoms could be
      explained by a failure to properly metacognitively monitor certain thought
      processes.

PMID- 22150423
TI  - IOC Consensus Conference on Nutrition in Sport, 25-27 October 2010, International
      Olympic Committee, Lausanne, Switzerland.

PMID- 22150420
TI  - Associations between congenital cryptorchidism in newborn boys and levels of
      dioxins and PCBs in placenta.
AB  - In animal studies, exposure to dioxins has been associated with disrupted
      development of the male reproductive system, including testicular maldescent.
      Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition,
      one previous case-control study has reported an association between congenital
      cryptorchidism and colostrum PCB levels. We performed a case-control study to
      evaluate whether congenital cryptorchidism in boys was associated with increased
      levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition,
      associations between placenta levels of these chemicals and reproductive hormone
      levels in boys at 3 months were studied. Placentas were collected in a Danish
      Finnish joint prospective cohort study on cryptorchidism (1997-2001). The boys
      were examined for cryptorchidism at birth and at 3 months. Altogether, 280
      placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129
      controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum
      samples taken at 3 months were analysed for reproductive hormones. No significant
      differences between cases and controls were observed in either country in dioxin
      WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and
      11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15
      pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels
      (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in
      Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant
      reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in
      placenta associated positively with infant LH levels. WHO-TEq levels of dioxins
      and PCBs and total-TEq levels were higher in Danish than Finnish samples. In
      conclusion, no association between placenta levels of dioxins or PCBs and
      congenital cryptorchidism was found. Significant country differences in chemical
      levels were observed.

PMID- 22150424
TI  - Nutrition for winter sports.
AB  - Winter sports are played in cold conditions on ice or snow and often at moderate
      to high altitude. The most important nutritional challenges for winter sport
      athletes exposed to environmental extremes include increased energy expenditure,
      accelerated muscle and liver glycogen utilization, exacerbated fluid loss, and
      increased iron turnover. Winter sports, however, vary greatly regarding their
      nutritional requirements due to variable physiological and physique
      characteristics, energy and substrate demands, and environmental training and
      competition conditions. What most winter sport athletes have in common is a
      relatively lean physique and high-intensity training periods, thus they require
      greater energy and nutrient intakes, along with adequate food and fluid before,
      during, and after training. Event fuelling is most challenging for cross-country
      skiers competing in long events, ski jumpers aiming to reduce their body weight,
      and those winter sport athletes incurring repeated qualification rounds and
      heats. These athletes need to ensure carbohydrate availability throughout
      competition. Finally, winter sport athletes may benefit from dietary and sport
      supplements; however, attention should be paid to safety and efficacy if
      supplementation is considered.

PMID- 22150425
TI  - Dietary protein for athletes: from requirements to optimum adaptation.
AB  - Opinion on the role of protein in promoting athletic performance is divided along
      the lines of how much aerobic-based versus resistance-based activity the athlete
      undertakes. Athletes seeking to gain muscle mass and strength are likely to
      consume higher amounts of dietary protein than their endurance-trained
      counterparts. The main belief behind the large quantities of dietary protein
      consumption in resistance-trained athletes is that it is needed to generate more
      muscle protein. Athletes may require protein for more than just alleviation of
      the risk for deficiency, inherent in the dietary guidelines, but also to aid in
      an elevated level of functioning and possibly adaptation to the exercise
      stimulus. It does appear, however, that there is a good rationale for
      recommending to athletes protein intakes that are higher than the RDA. Our
      consensus opinion is that leucine, and possibly the other branched-chain amino
      acids, occupy a position of prominence in stimulating muscle protein synthesis;
      that protein intakes in the range of 1.3-1.8 g . kg(-1) . day(-1) consumed as 3-4
      isonitrogenous meals will maximize muscle protein synthesis. These
      recommendations may also be dependent on training status: experienced athletes
      would require less, while more protein should be consumed during periods of high
      frequency/intensity training. Elevated protein consumption, as high as 1.8-2.0 g
      . kg(-1) . day(-1) depending on the caloric deficit, may be advantageous in
      preventing lean mass losses during periods of energy restriction to promote fat
      loss.

PMID- 22150426
TI  - IOC consensus statement on sports nutrition 2010.

PMID- 22150427
TI  - Fluid and electrolyte needs for training, competition, and recovery.
AB  - Fluids and electrolytes (sodium) are consumed by athletes, or recommended to
      athletes, for a number of reasons, before, during, and after exercise. These
      reasons are generally to sustain total body water, as deficits (hypohydration)
      will increase cardiovascular and thermal strain and degrade aerobic performance.
      Vigorous exercise and warm/hot weather induce sweat production, which contains
      both water and electrolytes. Daily water (4-10 L) and sodium (3500-7000 mg)
      losses in active athletes during hot weather exposure can induce water and
      electrolyte deficits. Both water and sodium need to be replaced to re-establish
      "normal" total body water (euhydration). This replacement can be by normal eating
      and drinking practices if there is no urgency for recovery. But if rapid recovery
      (<24 h) is desired or severe hypohydration (>5% body mass) is encountered,
      aggressive drinking of fluids and consuming electrolytes should be encouraged to
      facilitate recovery for subsequent competition.

PMID- 22150428
TI  - Dietary supplements for athletes: emerging trends and recurring themes.
AB  - Dietary supplements are widely used at all levels of sport. Changes in patterns
      of supplement use are taking place against a background of changes in the
      regulatory framework that governs the manufacture and distribution of supplements
      in the major markets. Market regulation is complicated by the increasing
      popularity of Internet sales. The need for quality control of products to ensure
      they contain the listed ingredients in the stated amount and to ensure the
      absence of potentially harmful substances is recognized. This latter category
      includes compounds prohibited under anti-doping regulations. Several
      certification programmes now provide testing facilities for manufacturers of both
      raw ingredients and end products to ensure the absence of prohibited substances.
      Athletes should carry out a cost-benefit analysis for any supplement they propose
      to use. For most supplements, the evidence is weak, or even completely absent. A
      few supplements, including caffeine, creatine, and bicarbonate, are supported by
      a strong research base. Difficulties arise when new evidence appears to support
      novel supplements: in recent years, beta-alanine has become popular, and the use
      of nitrate and arginine is growing. Athletes seldom wait until there is
      convincing evidence of efficacy or of safety, but caution is necessary to
      minimize risk.

PMID- 22150429
TI  - A method for defleshing human remains using household bleach.
AB  - Medical examiners and forensic anthropologists are often faced with the difficult
      task of removing soft tissue from the human skeleton without damaging the bones,
      teeth and, in some cases, cartilage. While there are a number of acceptable
      methods that can be used to remove soft tissue including macerating in water,
      simmering or boiling, soaking in ammonia, removing with scissors, knife, scalpel
      or stiff brush, and dermestid beetles, each has its drawback in time, safety, or
      potential to damage bone. This technical report using the chest plate of a
      stabbing victim presents a safe and effective alternative method for removing
      soft tissue from human remains, in particular the chest plate, following autopsy,
      without damaging or separating the ribs, sternum, and costal cartilage. This
      method can be used to reveal subtle blunt force trauma to bone, slicing and
      stabbing injuries, and other forms of trauma obscured by overlying soft tissue.
      Despite the published cautionary notes, when done properly household bleach (3-6%
      sodium hypochlorite) is a quick, safe, and effective method for examining
      cartilage and exposing skeletal trauma by removing soft tissue from human
      skeletal remains.

PMID- 22150430
TI  - Follow-up to "central and peripheral corneal iron deposits after implantation of
      a small-aperture corneal inlay for correction of presbyopia".

PMID- 22150431
TI  - Both p110alpha and p110beta isoforms of PI3K can modulate the impact of loss-of
      function of the PTEN tumour suppressor.
AB  - The PI3K (phosphoinositide 3-kinase) pathway is commonly activated in cancer as a
      consequence of inactivation of the tumour suppressor PTEN (phosphatase and tensin
      homologue deleted on chromosome 10), a major negative regulator of PI3K
      signalling. In line with this important role of PTEN, mice that are heterozygous
      for a PTEN-null allele (PTEN+/- mice) spontaneously develop a variety of tumours
      in multiple organs. PTEN is a phosphatase with selectivity for PtdIns(3,4,5)P3,
      which is produced by the class I isoforms of PI3K (p110alpha, p110beta, p110gamma
      and p110delta). Previous studies indicated that PTEN-deficient cancer cell lines
      mainly depend on p110beta, and that p110beta, but not p110alpha, controls mouse
      prostate cancer development driven by PTEN loss. In the present study, we
      investigated whether the ubiquitously expressed p110alpha can also functionally
      interact with PTEN in cancer. Using genetic mouse models that mimic systemic
      administration of p110alpha- or p110beta-selective inhibitors, we confirm that
      inactivation of p110beta, but not p110alpha, inhibits prostate cancer development
      in PTEN+/- mice, but also find that p110alpha inactivation protects from
      glomerulonephritis, pheochromocytoma and thyroid cancer induced by PTEN loss.
      This indicates that p110alpha can modulate the impact of PTEN loss in disease and
      tumourigenesis. In primary and immortalized mouse fibroblast cell lines, both
      p110alpha and p110beta controlled steady-state PtdIns(3,4,5)P3 levels and Akt
      signalling induced by heterozygous PTEN loss. In contrast, no correlation was
      found in primary mouse tissues between PtdIns(3,4,5)P3 levels, PI3K/PTEN genotype
      and cancer development. Taken together, our results from the present study show
      that inactivation of either p110alpha or p110beta can counteract the impact of
      PTEN inactivation. The potential implications of these findings for PI3K-targeted
      therapy of cancer are discussed.

PMID- 22150432
TI  - Mechanism and control of Genipa americana seed germination.
AB  - Genipa americana (Rubiaceae) is important for restoration of riparian forest in
      the Brazilian Cerrado. The objective was to characterize the mechanism and
      control of germination of G. americana to support uniform seedling production.
      Morphology and morphometrics of seeds, embryo and endosperm were assessed by
      light and scanning electron microscopy during germination. Imbibition and
      germination curves were generated and over the same time interval endosperm
      digestion and resistance were measured by puncture force analysis and activity
      assay of endo-beta-mannanase (EBM) in water and in abscisic acid (ABA). The gene
      encoding for EBM was partially cloned and its expression monitored by
      quantitative real-time-polymerase chain reaction. Embryos displayed growth prior
      to radicle protrusion. A two-phase increase in EBM activity coincided with the
      two stages of weakening of the micropylar endosperm. The second stage also
      coincided with growth of the embryo prior to radicle protrusion. Enzyme activity
      was initiated in the micropylar endosperm but spread to the lateral endosperm.
      ABA completely inhibited germination by inhibiting embryo growth, the second
      stage of weakening and expression of the EBM gene, but EBM activity was not
      significantly inhibited. This suggests that a specific isoform of the enzyme is
      involved in endosperm weakening. EBM may cause a general 'softening' of
      micropylar endosperm cell walls, allowing the embryo to puncture the endosperm as
      the driving force of the decrease in puncture force.

PMID- 22150433
TI  - Mimicry and just world beliefs: mimicking makes men view the world as more
      personally just.
AB  - People's just world beliefs are related to how they feel and behave towards
      others: the stronger people hold beliefs that the world treats them fairly, the
      more they feel and act pro-socially towards others. It is conceivable, therefore,
      that pro-social feelings and behaviours towards others can strengthen people's
      personal belief in a just world, especially when people expect these positive
      feelings to be returned. Because mimicry enhances pro-social feelings towards
      others, we argue that mimicry may strengthen peoples' personal just world beliefs
      via positive feelings for the mimicked person and the expectation that these
      positive feelings are returned. Moreover, we expect these effects to be more
      pronounced for men because men have stronger reciprocity beliefs than women. The
      results of three studies supported this line of reasoning, showing that mimicry
      made men believe more strongly that the world is personally just to them. Further
      support for our line of reasoning was obtained by positive feelings for the
      (non)mimicked person (Study 2) and reciprocity beliefs (Study 3) mediating the
      effects. Taken together, the findings suggest that mimicry makes men view the
      world as more just. 

PMID- 22150434
TI  - Validation of a tool to assess medication treatment satisfaction in patients with
      Type 2 diabetes: the Diabetes Medication System Rating Questionnaire (DMSRQ).
AB  - AIM: To assess the reliability and validity of the Diabetes Medication System
      Rating Questionnaire among 537 US adults with Type 2 diabetes using five
      different diabetes medication regimens (oral agents with and without insulin;
      insulin only by syringe and by pen; glucagon-like peptide 1 agents). METHODS: The
      Diabetes Medication System Rating Questionnaire assesses the treatment experience
      of patients using any diabetes medication system that uses nine measures
      (Convenience, Negative Events, Interference, Self-Monitoring of Blood Glucose
      Burden, Efficacy, Social Burden, Psychological Well-Being, Treatment
      Satisfaction, Treatment Preference). It was administered via an initial online
      survey, along with other validated measures of treatment satisfaction and
      medication adherence, with a retest administered within 2 weeks. Participants
      were 52.5% male, 57.4% aged 40-64 years, 83.6% white and 95.2% non-Hispanic. Most
      (75.6%) had attended college and 58.3% had been diagnosed with diabetes for more
      than 10 years. RESULTS: Median inter-item agreement was 0.86. Median test-retest
      reliability was also 0.86. All correlations between Diabetes Medication System
      Rating Questionnaire measures and criterion measures of treatment satisfaction
      and adherence were statistically significant (P<0.01) in the expected direction.
      Correlations between Diabetes Medication System Rating Questionnaire and the
      corresponding criterion measures of treatment satisfaction ranged from 0.349 to
      0.629 (absolute values; interpolated median 0.568); correlations of the same
      measures with adherence ranged from 0.384 to 0.450 (absolute values; mean 0.411).
      Diabetes Medication System Rating Questionnaire measures differentiated among
      groups taking different medications and those using different delivery systems
      for the same medication. CONCLUSIONS:   This study suggests that the Diabetes
      Medication System Rating Questionnaire has good reliability and validity and
      provides a more comprehensive set of measures than existing medication
      satisfaction questionnaires.

PMID- 22150435
TI  - Flow characteristics and spillage mechanisms of wall-mounted and jet-isolated
      range hoods subject to influence from cross draft.
AB  - The effects of draft on the flow and spillage characteristics of wall-mounted and
      jet-isolated range hoods were investigated. A specially designed draft generator
      that could supply low-swirl air current was used to provide "cross draft" from
      three directions, lateral (theta = 0(o)), oblique (theta = 45(o)), and front
      (theta = 90(o)), with respect to the center point of the range hoods. Flow
      characteristics of oil mist were inspected through visualization of smoke flows
      with light scattering (laser light sheet-assisted visualization of smoke flow).
      The leakage mechanisms, which were closely related to the flow features, were
      studied by examining both movies and still pictures showing smoke-flow evolution.
      The sulfur hexafluoride tracer gas concentration detection method was employed to
      measure the capture indices. The results showed that the lateral draft pushed the
      pollutants generated under the hood in the opposite direction and induced serious
      spillage. The oblique draft pushed the pollutants toward both the rear wall and
      opposite side and induced more serious spillage than did the lateral draft. The
      frontal draft forced the pollutants to bifurcate into streams moving toward the
      left and the right, and induced the most serious pollutant spillage among the
      three tested drafts. Pollutant spillage became critically significant as the
      cross draft velocity was increased to greater than 0.2 m/sec. Spillage of
      pollutants increased as the velocity of the cross draft was increased. Increasing
      the suction flow rate of the range hood may increase resistance to the draft, but
      the benefits were limited at draft velocities greater than 0.2 m/sec. Both range
      hoods had a similarly low capture index under the influence of the lateral draft.
      For the oblique and frontal drafts, the jet-isolated range hood demonstrated a
      higher capture index than did the wall-mounted range hood.

PMID- 22150436
TI  - Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a
      retrospective, multicenter, cohort study.
AB  - Therapeutic options for superficial infantile hemangiomas (IH) are limited.
      Recently, timolol maleate gel, a topical nonselective beta-blocker, has been
      reported as a potentially effective treatment for superficial IH. This study is
      an extension of a previously published pilot study designed to further
      investigate the efficacy and safety and to identify predictors of good response
      of topical 0.5% or 0.1% timolol maleate gel-forming solution. This was a
      retrospective cohort study including patients enrolled from five centers.
      Patients were included if they were treated with timolol maleate 0.1% or 0.5% gel
      forming solution and had photographic documentation of the IH and at least one
      follow-up visit. Patients with concomitant active treatment using other IH
      treatments were excluded. The primary endpoint was change in the appearance of IH
      as evaluated using a visual analog scale (VAS). Data from 73 subjects were
      available for final analysis. Timolol maleate gel-forming solution 0.5% was used
      in 85% (62/73) of patients, the remainder being treated with 0.1%. The median age
      at treatment initiation was 4.27 months (interquartile range [IQR] 2.63-7.21
      mos), and patients were treated for a mean of 3.4 +/- 2.7 months. All patients
      except one improved, with a mean improvement of 45 +/- 29.5%. Predictors of
      better response were superficial type of hemangioma (p = 0.01), 0.5% timolol
      concentration (p = 0.01), and duration of use longer than 3 months (p = 0.04).
      Sleeping disturbance was noted in one patient. This study further demonstrates
      the efficacy and tolerability of topical timolol maleate and gradual improvement
      with longer treatment in patients with superficial IH.

PMID- 22150437
TI  - Origins of groundwater inferred from isotopic patterns of the Badain Jaran
      Desert, northwestern China.
AB  - There are many viewpoints about the sources of groundwater in the Badain Jaran
      Desert (BJD), such as precipitation and snowmelt from the Qilian Mountains (the
      upper reaches [UR] of the Heihe River Basin [HRB]) and precipitation from the BJD
      and the Yabulai Mountains. To understand the source of the groundwater of the BJD
      and their possible associations with nearby bodies of water, we analyzed
      variations of stable isotope ratios (deltaD and delta(18) O) and the deuterium
      excess (d-excess) of groundwater and precipitation in the BJD, of groundwater,
      precipitation, river and spring water in the UR, and of groundwater and river
      water in the middle and lower reaches (MR and LR) of the HRB. In addition, the
      climatic condition under which the groundwater was formed in the BJD was also
      discussed. We found obvious differences in deltaD, delta(18) O, and d-excess
      among groundwater in the BJD, nearby water bodies and the HRB. The groundwater
      deltaD-delta(18) O equation for the BJD was deltaD = 4.509delta(18) O-30.620,
      with a slope and intercept similar to that of nearby areas (4.856 and -29.574),
      indicating a strong evaporation effect in the BJD and its surrounding areas. The
      equation's slope of the BJD was significantly lower than those of HRB groundwater
      (6.634), HRB river water (6.202), precipitation in the BJD and Youqi (7.841), and
      the UR of the HRB (7.839). The d-excess (-17.50/00) of the BJD was significantly
      lower than those of nearby groundwater (-7.40/00), HRB groundwater (12.10/00),
      precipitation in the BJD (5.70/00) and in the UR of the HRB (15.20/00), and HRB
      river water (14.40/00). The spatial patterns of delta(18) O and d-excess values
      in the BJD suggest mixing and exchange of groundwater between the BJD and
      neighboring regions, but no hydraulic relationship between the BJD groundwater
      and water from more distant regions except Outer Mongolia, which is north of the
      BJD. Moreover, we conclude that there is little precipitation recharge to
      groundwater because of the obvious d-excess difference between groundwater and
      local precipitation, low precipitation, and high evaporation rates. The
      abnormally negative d-excess values in groundwater of the BJD indicate that this
      water was formed in the past under higher relative humidity and lower
      temperatures than modern values.

PMID- 22150438
TI  - Detection of hazardous weight-loss substances in adulterated slimming
      formulations using ultra-high-pressure liquid chromatography with diode-array
      detection.
AB  - The presence on the market of illegal products for slimming purposes or the
      treatment of overweight is a public health issue. These products may contain
      illicit chemicals in order to improve their effectiveness. Some of these weight
      loss compounds are responsible for adverse events, including fatal outcomes. A
      general strategy for the analysis of any suspect formulation begins with a large
      screening for the general search of a wide range of compounds. A methodology for
      the qualitative and quantitative determination of 34 compounds in slimming
      preparations (such as dietary supplements or medicinal products) was used for the
      control of slimming formulations from the market, including over the Internet.
      The fast liquid chromatography system (ultra-high-pressure liquid chromatography)
      used a gradient of solvent (phosphate buffer and acetonitrile), a C18 endcapped
      column and a diode array detector. This system allows dual identification based
      on retention time and UV spectra. The analytical method is simple, fast and
      selective since 34 weight-loss compounds can be detected in a 15-min run time.
      Thus, 32 commercial slimming formulations were analysed using this method,
      allowing the detection and quantification of hazardous active substances:
      caffeine, clenbuterol, nicotinamide, phenolphthalein, rimonabant, sibutramine,
      didesmethylsibutramine, synephrine and yohimbine.

PMID- 22150439
TI  - Vascular adhesion protein-1 and syndecan-1 in septic shock.
AB  - BACKGROUND: Constituents of vascular endothelial surface layer (glycocalyx), e.g.
      an anchor protein syndecan-1 (SDC-1), can be detected in plasma in many
      inflammatory conditions. In inflammation, vascular adhesion protein-1 (VAP-1) is
      rapidly translocated to the apical side of the endothelial cells and may be
      released to plasma in a soluble form. We hypothesized that glycocalyx injury
      coincides with VAP-1 activation on endothelial cells. To test the hypothesis, we
      measured SDC-1 and VAP-1 levels in 20 patients with septic shock. METHODS: A
      prospective observational study was conducted in two multidisciplinary critical
      care units in two tertiary academic teaching hospitals with 20 mechanically
      ventilated adult patients with septic shock, on days 1 and 4 of treatment. Twenty
      healthy adults were enrolled as a control group. Plasma SDC-1 content, serum VAP
      1 activity, platelets, and leukocyte count were measured in septic shock group at
      baseline and at 72 h and compared with those of healthy controls. RESULTS: VAP-1
      activity and SDC-1 content were significantly increased in septic patients' group
      (P < 0.01) in comparison with controls. VAP-1 activity and SDC-1 content
      correlated positively to each other, and negatively to platelet count. In the
      septic shock group SDC-1 correlated on day 1 to SOFA score. CONCLUSIONS: We found
      increased VAP-1 activity and SDC-1 content in critically ill patients with septic
      shock. Based on our results, the role of VAP-1 in shock pathogenesis should be
      studied with semicarbazide-sensitive amine oxidase activity blocking agents and
      substrate affinity testing.

PMID- 22150440
TI  - Evaluation of heparanase and matrix metalloproteinase-9 in patients with
      cutaneous malignant melanoma.
AB  - Elevated heparanase and matrix metalloproteinase (MMP)-9, frequently found in
      human cancer, is a major cause of degradation of the extracellular matrix (ECM)
      and basement membrane (BM), thus facilitating tumor cell migration and invasion.
      Although a lot of work has been done, the role of heparanase and MMP-9 has not
      been delineated in skin cancer progression. The purpose of this study was to do
      such an exploration. To investigate the role of heparanase and MMP-9 in cutaneous
      malignant melanoma (CMM) development, we performed immunohistochemical analysis
      to detect the alternation of these two factors in paraffin-embedded biopsy
      specimens of normal skin, junctional nevi and CMM. It is interesting to note that
      the expression profile of heparanase and MMP-9 was similar. Contrary to negative
      staining in normal skin, overexpression of heparanase and cytoplasmic MMP-9 was
      observed in as many as 70% of CMM, whereas only 10% of the junctional nevi
      exhibited faint staining (P = 0.0005, P = 0.0000). Considering the lymph node
      (LN) metastasis, the expression of the two factors is significantly higher in LN
      positive lesions than that in LN-negative lesions (P = 0.0295, P = 0.0013).
      Meanwhile, there was positive correlation between the expression of MMP-9 and
      heparanase (r = 0.689, P = 0.003). The first expression of MMP-9 and heparanase
      occurs at benign lesions. However, the significantly increased expression in
      advanced CMM stages, particularly in LN-positive metastasis lesions, might
      synergistically contribute to degradation of ECM and BM, therefore promoting
      carcinogenesis and metastasis.

PMID- 22150442
TI  - Impact of carbon dioxide enrichment on the responses of maize leaf transcripts
      and metabolites to water stress.
AB  - Maize (Zea mays) was grown in indoor chambers with ambient (38 Pa) and elevated
      (70 Pa) CO(2) . Drought treatments were imposed 17 days after sowing by
      withholding nutrient solution. Decreases of soil water content, leaf water
      potential, net CO(2)  assimilation and stomatal conductance as a result of
      drought were delayed approximately 2 days by CO(2)  enrichment. Concentrations of
      28 of 33 leaf metabolites were altered by drought. Soluble carbohydrates,
      aconitate, shikimate, serine, glycine, proline and eight other amino acids
      increased, and leaf starch, malate, fumarate, 2-oxoglutarate and seven amino
      acids decreased with drought. Drought-dependent decreases of nitrate, alanine and
      aspartate were impacted by limiting nitrogen. Transcript levels of 14 stress
      related maize genes responded to drought but this was delayed or modified by
      CO(2)  enrichment. Overall, CO(2)  enrichment eliminated many early responses of
      maize metabolites and transcripts to water stress but was less effective when
      drought was severe. Four metabolite groupings were identified by clustering
      analysis. These groupings included compounds that decreased with water stress,
      compounds involved in osmotic adjustment and aromatic compounds that alleviate
      oxidative stress. Metabolite changes also supported the suggestion that water
      stress inhibited C(4)  photosynthesis and induced photorespiration.

PMID- 22150443
TI  - The cutaneous trunci muscle reflex: a predictor of recovery in dogs with acute
      thoracolumbar myelopathies caused by intervertebral disc extrusions.
AB  - OBJECTIVE: To determine whether changes in the cutaneous trunci muscle (CTM)
      reflex are an early predictor of outcome in dogs with severe acute thoracolumbar
      intervertebral disc extrusion (IVDE). STUDY DESIGN: Multicenter prospective
      cohort study. ANIMALS: Dogs (n = 36) with acute IVDE causing paraplegia, loss of
      nociception in pelvic limbs and tail, and an abnormal CTM reflex postoperatively.
      METHODS: The caudal border of the CTM reflex was established 24 hours after
      surgery and at discharge, and was reported as moving cranially, caudally, or
      staying static. Dogs were re-evaluated at 12-20 weeks and at 7-36 months
      postoperatively. Outcome was classified as improved or unimproved, successful or
      unsuccessful, and ascending myelomalacia or not, and compared with early movement
      of the CTM reflex by construction of contingency tables and performing a Fisher's
      exact test. RESULTS: By discharge (mean, 4.7 days; SD = 2.10), CTM reflex
      progression was caudal in 19 dogs, static in 11, and cranial in 6. Five of 6 dogs
      with cranial movement developed ascending myelomalacia (P < .0001). Seventeen of
      19 dogs with caudal movement showed an improvement by 12-20 weeks (P = .0046) and
      none developed ascending myelomalacia (P = .0013). CONCLUSIONS: Postoperative
      changes of the caudal border of the CTM reflex are an early indicator of outcome
      in dogs with severe acute IVDE. Cranial movement of the CTM reflex is
      significantly associated with the development of ascending myelomalacia. Caudal
      movement is significantly associated with improvement, but not associated with a
      long-term successful outcome.

PMID- 22150441
TI  - Prevalence of unplanned hospitalizations caused by adverse drug reactions in
      older veterans.
AB  - OBJECTIVES: To describe the prevalence of unplanned hospitalizations caused by
      adverse drug reactions (ADRs) in older veterans and to examine the association
      between this outcome and polypharmacy after controlling for comorbidities and
      other patient characteristics. DESIGN: Retrospective cohort. SETTING: Veterans
      Affairs Medical Centers. PARTICIPANTS: Six hundred seventy-eight randomly
      selected unplanned hospitalizations of older (aged >= 65) veterans between
      October 1, 2003, and September 30, 2006. MEASUREMENTS: Naranjo ADR algorithm, ADR
      preventability, and polypharmacy (0-4, 5-8, and >=9 scheduled medications).
      RESULTS: Seventy ADRs involving 113 drugs were found in 68 (10%) hospitalizations
      of older veterans, of which 25 (36.8%) were preventable. Extrapolating to the
      population of more than 2.4 million older veterans receiving care during the
      study period, 8,000 hospitalizations may have been unnecessary. The most common
      ADRs that occurred were bradycardia (n = 6; beta-blockers, digoxin), hypoglycemia
      (n = 6; sulfonylureas, insulin), falls (n = 6; antidepressants, angiotensin
      converting enzyme inhibitors), and mental status changes (n = 6; anticonvulsants,
      benzodiazepines). Overall, 44.8% of veterans took nine or more outpatient
      medications and 35.4% took five to eight. Using multivariable logistic regression
      and controlling for demographic, health-status, and access-to-care variables,
      polypharmacy (>=9 and 5-8) was associated with greater risk of ADR-related
      hospitalization (adjusted odds ratio (AOR) = 3.90, 95% confidence interval (CI) =
      1.43-10.61 and AOR = 2.85, 95% CI = 1.03-7.85, respectively). CONCLUSION: ADRs,
      determined using a validated causality algorithm, are a common cause of unplanned
      hospitalization in older veterans, are frequently preventable, and are associated
      with polypharmacy.

PMID- 22150444
TI  - A new derivative of valproic acid amide possesses a broad-spectrum antiseizure
      profile and unique activity against status epilepticus and organophosphate
      neuronal damage.
AB  - PURPOSE: sec-Butyl-propylacetamide (SPD) is a one-carbon homolog of valnoctamide
      (VCD), a central nervous system (CNS)-active amide derivative of valproic acid
      (VPA) currently in phase II clinical trials. The study reported herein evaluated
      the anticonvulsant activity of SPD in a battery of rodent seizure and epilepsy
      models and assessed its efficacy in rat and guinea pig models of status
      epilepticus (SE) and neuroprotection in an organotypic hippocampal slice model of
      excitotoxic cell death. METHODS: The anticonvulsant activity of SPD was evaluated
      in several rodent seizure and epilepsy models, including maximal electroshock
      (MES), 6-Hz psychomotor; subcutaneous (s.c.) metrazol-, s.c. picrotoxin, s.c.
      bicuculline, and audiogenic, corneal, and hippocampal kindled seizures following
      intraperitoneal administration. Results obtained with SPD are discussed in
      relationship to those obtained with VPA and VCD. SPD was also evaluated for its
      ability to block benzodiazepine-resistant SE induced by pilocarpine (rats) and
      soman (rats and guinea pigs) following intraperitoneal administration. SPD was
      tested for its ability to block excitotoxic cell death induced by the glutamate
      agonists N-methyl-D-aspartate (NMDA) and kainic acid (KA) using organotypic
      hippocampal slices and SE-induced hippocampal cell death using FluoroJade B
      staining. The cognitive function of SPD-treated rats that were protected against
      pilocarpine-induced convulsive SE was examined 10-14 days post-SE using the
      Morris water maze (MWM). The relationship between the pharmacokinetic profile of
      SPD and its efficacy against soman-induced SE was evaluated in two parallel
      studies following SPD (60 mg/kg, i.p.) administration in the soman SE rat model.
      KEY FINDINGS: SPD was highly effective and displayed a wide protective index (PI
      = median neurotoxic dose/median effective dose [TD(50)/ED(50)]) in the
      standardized seizure and epilepsy models employed. The wide PI values of SPD
      demonstrate that it is effective at doses well below those that produce
      behavioral impairment. Unlike VCD, SPD also displayed anticonvulsant activity in
      the rat pilocarpine model of SE. Thirty minutes after the induction of SE, the
      calculated rat ED(50) for SPD against convulsive SE in this model was 84 mg/kg.
      SPD was not neuroprotective in the organotypic hippocampal slice preparation;
      however, it did display hippocampal neuroprotection in both SE models and
      cognitive sparing in the MWM, which was associated with its antiseizure effect
      against pilocarpine-induced SE. When administered 20 and 40 min after SE onset,
      SPD (100-174 mg/kg) produced long-lasting efficacy (e.g., 4-8 h) against soman
      induced convulsive and electrographic SE in both rats and guinea pigs. SPD ED(50)
      values in guinea pigs were 67 and 92 mg/kg when administered at SE onset or 40
      min after SE onset, respectively. Assuming linear pharmacokinetics (PK), the PK
      PD (pharmacodynamic) results (rats) suggests that effective SPD plasma levels
      ranged between 8 and 40 mg/L (20 min after the onset of soman-induced seizures)
      and 12-50 mg/L (40 min after the onset of soman-induced seizures). The time to
      peak (t(max)) pharmacodynamic effect (PD-t(max)) occurred after the PK-t(max),
      suggesting that SPD undergoes slow distribution to extraplasmatic sites, which is
      likely responsible for antiseizure activity of SPD. SIGNIFICANCE: The results
      demonstrate that SPD is a broad-spectrum antiseizure compound that blocks SE
      induced by pilocarpine and soman and affords in vivo neuroprotection that is
      associated with cognitive sparing. Its activity against SE is superior to that of
      diazepam in terms of rapid onset, potency, and its effect on animal mortality and
      functional improvement.

PMID- 22150450
TI  - Modeling exotic highly pathogenic avian influenza virus entrance risk through air
      passenger violations.
AB  - The highly pathogenic avian influenza virus (HPAIV) is able to survive in poultry
      products and could be carried into a country by air travelers. An assessment
      model was constructed to estimate the probability of the exotic viable HPAIV
      entering Taiwan from two neighboring areas through poultry products carried
      illegally by air passengers at Taiwan's main airports. The entrance risk was
      evaluated based on HPAIV-related factors (the prevalence and the incubation
      period of HPAIV; the manufacturing process of poultry products; and the
      distribution-storage-transportation factor event) and the passenger event.
      Distribution functions were adopted to simulate the probabilities of each HPAIV
      factor. The odds of passengers being intercepted with illegal poultry products
      were estimated by logistic regression. The Monte Carlo simulation established
      that the risk caused by HPAIV-related factors from area A was lower than area B,
      whereas the entrance risk by the passenger event from area A was similar to area
      B. Sensitivity analysis showed that the incubation period of HPAIV and the
      interception of passenger violations were major determinants. Although the result
      showed viable HPAIV was unlikely to enter Taiwan through meat illegally carried
      by air passengers, this low probability could be caused by incomplete animal
      disease data and modeling uncertainties. Considering the negative socioeconomic
      impacts of HPAIV outbreaks, strengthening airport quarantine measures is still
      necessary. This assessment provides a profile of HPAIV entrance risk through air
      travelers arriving from endemic areas and a feasible direction for quarantine and
      public health measures.

PMID- 22150449
TI  - Phosphatidylethanol (PEth) as a biomarker of alcohol consumption in HIV-positive
      patients in sub-Saharan Africa.
AB  - BACKGROUND: Alcohol is heavily consumed in sub-Saharan Africa and affects HIV
      transmission and treatment and is difficult to measure. Our goal was to examine
      the test characteristics of a direct metabolite of alcohol consumption,
      phosphatidylethanol (PEth). METHODS: Persons infected with HIV were recruited
      from a large HIV clinic in southwestern Uganda. We conducted surveys and breath
      alcohol concentration (BRAC) testing at 21 daily home or drinking establishment
      visits, and blood was collected on day 21 (n = 77). PEth in whole blood was
      compared with prior 7-, 14-, and 21-day alcohol consumption. RESULTS: (i) The
      receiver operator characteristic area under the curve (ROC-AUC) was highest for
      PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval
      [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI:
      76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC
      AUC of PEth versus any 21-day alcohol consumption did not vary with age, body
      mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral
      therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth
      measurements were correlated with several measures of alcohol consumption,
      including number of drinking days in the prior 21 days (Spearman r = 0.74, p <
      0.001) and BRAC (r = 0.75, p < 0.001). CONCLUSIONS: The data add support to the
      body of evidence for PEth as a useful marker of alcohol consumption with high ROC
      AUC, sensitivity, and specificity. Future studies should further address the
      period and level of alcohol consumption for which PEth is detectable.

PMID- 22150452
TI  - Treatment of mental slowness: how to evaluate treatment effects. A systematic
      review of outcome measures.
AB  - Brain-damaged patients with slow mental processes may be taught compensatory
      strategies that might enable them to minimise disabilities and participation
      problems in daily life. The effects of the application of compensatory strategies
      should be measured in these domains of functioning. We systematically reviewed
      existing outcome measures used to evaluate the consequences of mental slowness.
      We classified measures into four categories: (1) standardised neuropsychological
      tests; (2) tests or questionnaires measuring general cognitive impairment; (3)
      measures of general everyday functioning; and (4) measures of everyday
      consequences of mental slowness. The majority of measures for mental slowness
      focus on performance in specific cognitive tasks. We found seven studies that
      used nine measures which focused on task-related or perceived limitations in
      everyday functioning. We discuss a series of reasons why measures of the
      perception of slowness (including the perceived consequences of slowness) and the
      performance in everyday activities should be used. Such measures may be more
      likely to detect change or differences in performance and are certainly more
      relevant to patients.

PMID- 22150451
TI  - Imagine that: self-imagination improves prospective memory in memory-impaired
      individuals with neurological damage.
AB  - Recent research has demonstrated that "self-imagination" - a mnemonic strategy
      developed by Grilli and Glisky  (2010)  - enhances episodic memory in memory
      impaired individuals with neurological damage more than traditional cognitive
      strategies, including semantic elaboration and visual imagery. The present study
      investigated the effect of self-imagination on prospective memory in individuals
      with neurologically based memory deficits. In two separate sessions, 12 patients
      with memory impairment took part in a computerised general knowledge test that
      required them to answer multiple choice questions (i.e., ongoing task) and press
      the "1" key when a target word appeared in a question (i.e., prospective memory
      task). Prior to the start of the general knowledge test in each session,
      participants attempted to encode the prospective memory task with one of two
      strategies: self-imagination or rote-rehearsal. The findings revealed a "self
      imagination effect (SIE)" in prospective memory as self-imagining resulted in
      better prospective memory performance than rote-rehearsal. These results
      demonstrate that the mnemonic advantage of self-imagination extends to
      prospective memory in memory-impaired individuals with neurological damage and
      suggest that self-imagination has potential in cognitive rehabilitation.

PMID- 22150453
TI  - Development of the Brief Assessment of Prospective Memory (BAPM) for use with
      traumatic brain injury populations.
AB  - Impairment of prospective memory (PM) is a common problem following traumatic
      brain injury (TBI) which can affect functional outcomes. PM failures in everyday
      life can be assessed using self-report questionnaires; however, existing measures
      tend to be lengthy, which may be problematic for individuals with fatigue and
      other cognitive impairments. This study aimed to develop a short form of the
      Comprehensive Assessment of Prospective Memory (CAPM) and examine its
      psychometric properties. Using theoretical and statistical considerations, the
      number of items on the CAPM was reduced to 16 including equal numbers
      representing the basic activities of daily living (BADL) and instrumental
      activities of daily living (IADL) subscales. The psychometric properties of the
      new measure, named the Brief Assessment of Prospective Memory (BAPM), were
      examined by secondary analysis of data from two samples of community dwelling
      adults (aged 17 to 91 years, n = 527, and 15 to 60 years, n = 95) with no history
      of brain injury, and a sample of rehabilitation patients with moderate to severe
      TBI (n = 45). Results indicate that the BAPM has a robust factor structure,
      strong agreement with the original CAPM, acceptable internal consistency and test
      retest reliability, and evidence of criterion-related validity with psychosocial
      integration as the point of reference for people with TBI.

PMID- 22150454
TI  - Prospective memory rehabilitation based on visual imagery techniques.
AB  - Despite the frequency of prospective memory (PM) problems in the traumatic brain
      injury (TBI) population, there are only a few rehabilitation programmes that have
      been specifically designed to address this issue, other than those using external
      compensatory strategies. In the present study, a PM rehabilitation programme
      based on visual imagery techniques expected to strengthen the cue-action
      association was developed. Ten moderate to severe chronic TBI patients learned to
      create a mental image representing the association between a prospective cue and
      an intended action within progressively more complex and naturalistic PM tasks.
      We hypothesised that compared to TBI patients (n = 20) who received a short
      session of education (control condition), TBI patients in the rehabilitation
      group would exhibit a greater improvement on the event-based than on the time
      based condition of a PM ecological task. Results revealed however that this
      programme was similarly beneficial for both conditions. TBI patients in the
      rehabilitation group and their relatives also reported less everyday PM failures
      following the programme, which suggests generalisation. The PM improvement
      appears to be specific since results on cognitive control tasks remained similar.
      Therefore, visual imagery techniques appear to improve PM functioning by
      strengthening the memory trace of the intentions and inducing an automatic recall
      of the intentions.

PMID- 22150460
TI  - Impact of acetaldehyde- and pyruvic acid-bound sulphur dioxide on wine lactic
      acid bacteria.
AB  - AIMS: To investigate the impact of acetaldehyde- and pyruvic acid-bound sulphur
      dioxide on wine lactic acid bacteria (LAB). METHODS AND RESULTS: Growth studies
      were performed where Oenococcus oeni, Pediococcus parvulus, Ped. damnosus and
      Lactobacillus hilgardii were inoculated into media containing various
      concentrations of acetaldehyde or pyruvic acid and an equimolar concentration of
      SO(2) at pH 3.50 and 3.70. Low concentrations of acetaldehyde- and pyruvic acid
      bound SO(2) were inhibitory to the growth of all bacteria although acetaldehyde
      bound SO(2) was generally more inhibitory than pyruvic acid-bound SO(2).
      Inhibition was greater at pH 3.50 than 3.70, and Lact. hilgardii was the most
      sensitive to acetaldehyde-bound SO(2), while O. oeni was the most sensitive to
      pyruvic acid-bound SO(2). Degradation of SO(2)-bound acetaldehyde was observed
      for all LAB, and aside from O. oeni, there was also complete degradation of SO(2)
      bound pyruvic acid at both pH values. O. oeni only degraded pyruvic acid at pH
      3.70. Degradation of SO(2)-bound acetaldehyde or pyruvic acid did not correlate
      with bacterial growth as inhibition was always observed in media containing bound
      SO(2). CONCLUSIONS: Acetaldehyde- and pyruvic acid-bound SO(2) were inhibitory to
      wine LAB growth at concentrations as low as 5 mg l(-1). Despite this inhibition,
      all wine LAB degraded SO(2)-bound acetaldehyde and pyruvic acid suggesting that
      bound SO(2) may have a bacteriostatic rather than bacteriocidal action.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Sulphur dioxide bound to acetaldehyde or
      pyruvic acid is inhibitory to growth of wine LAB and must be considered when
      conducting the malolactic fermentation or controlling the growth of spoilage
      bacteria such as Pediococcus and Lactobacillus.

PMID- 22150461
TI  - The experimental and case study of needle marks on the speedometer as the
      physical evidence for the collision speed analysis.
AB  - The collision speed is important in accident analysis, and needle marks can be
      helpful as the physical evidence. The deceleration impact system has been built
      to analyze the mechanics of the needle and the gauge plate. Two isolated groups
      were designed to record the speed values under the same sample labels from real
      crashes. The visualization platform was built for the first group to collect
      needle marks. The second group recorded the speed values by other methods. The
      collision deceleration, the gauge plate materials, and the collision directions
      determine the forming of the needle marks. There were eight positive results from
      the 23 effective samples (12 frontal, four side, and seven rear), with
      discernible tip and/or middle marks on gauge plates. Multiple marks have been
      distinguished effectively. The low- and high-speed impacts have no obvious
      differences for real needle marks. It is more accurate for frontal impacts.

PMID- 22150462
TI  - Anti-CCP and RF IgM: predictors of impaired endothelial function in rheumatoid
      arthritis patients.
AB  - OBJECTIVE: To determine whether the presence of anti-cyclic citrullinated peptide
      (anti-CCP) antibodies and rheumatoid factor immunoglobulin M (RF IgM) is
      associated with endothelial dysfunction in patients with rheumatoid arthritis
      (RA). METHODS: We studied the presence of anti-CCP antibodies and RF IgM and
      endothelial function in terms of the reactive hyperaemic index (RHI) in 53
      consecutive RA patients. Endothelial function was measured by using a finger
      plethysmograph. RESULTS: RHI was significantly lower in anti-CCP-positive RA
      patients (n = 33, RHI = 1.78, SD = 0.30) than in anti-CCP-negative RA patients (n
      = 20, RHI = 2.19, SD = 0.59; p = 0.008). A similar result was found in RF IgM
      positive patients (n  =  34, RHI = 1.77, SD = 0.30) vs. RF IgM-negative patients
      (n = 19, RHI = 2.23, SD = 0.58; p = 0.003). There were no significant differences
      between the groups regarding age, gender, traditional cardiovascular risk
      markers, Disease Activity Score using 28 joint counts (DAS28), C-reactive protein
      (CRP), erythrocyte sedimentation rate (ESR), extra-articular manifestations
      (EAMs), use of glucocorticosteroids, statins, angiotensin-converting enzyme (ACE)
      inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSION: The
      presence of anti-CCP antibodies and RF IgM was related to impaired endothelial
      function independent of other cardiovascular risk factors in RA patients. Thus,
      these autoantibodies might reflect an early reversible stage of the
      atherosclerotic process, and may indicate increased risk of cardiovascular
      disease (CVD). Further studies are needed to explore whether anti-CCP antibodies
      and RF IgM may act directly or indirectly to cause endothelial dysfunction, or
      merely reflect endothelial dysfunction in RA patients.

PMID- 22150463
TI  - Hepatoportal sclerosis in childhood: some presenting with cholestatic features (a
      re-evaluation of 12 children).
AB  - Hepatoportal sclerosis (HPS) is a syndrome of obscure etiology, and is one of the
      causes of noncirrhotic portal hypertension (PH). We aimed to investigate this
      heterogeneous group of patients whose presentation showed cholestatic features,
      histopathologically. Between 1999 and 2009, 12 children diagnosed with HPS were
      retrospectively evaluated. HPS was diagnosed with evidence of PH, noncirrhotic
      liver biopsy with typical histopathologic findings, and exclusion of other
      possible causes of PH. The data was obtained from pathology reports and
      microscopic slides. In histopathological re-evaluation fibrosis state, aberrant
      portal vessels, portal tract dilation and inflammation, ductular reaction,
      regenerative nodular hyperplasia, acinar transformation, presence of bile
      pigment, and cholangitis were noted. Serum alanine aminotransferase, aspartate
      aminotransferase, gamma-glutamyl, alkaline phosphatase, bilirubin, and albumin
      levels, presentation patterns, and radiologic findings were assessed. Familial
      relationship degrees were also investigated. Twelve patients (9 boys, 3 girls; 3
      180 months) were re-evaluated. Two pairs of the patients were siblings. Parents
      of 7 patients were consanguine. The most common presenting symptom was abdominal
      distension. Histopathologically, all patients had hepatoportal sclerosis/intimal
      fibrous thickening of portal vein and periportal fibrosis, acinar transformation,
      and regenerative nodules not surrounded by fibrous septae. Eight patients had
      vascular aberrations, 7 had ductular reaction, 1 showed mild cholangitis, and 1
      had canalicular bile pigment. We conclude that genetic predisposition might be a
      possible factor for HPS development in Turkish patients and it should be kept in
      mind that cholestatic features noticed in histopathological evaluation may
      represent a variant group in the spectrum of HPS.

PMID- 22150465
TI  - Proofiness infopinion truthiness: "drug treatment," "alcohol treatment".

PMID- 22150464
TI  - Foetal and post-natal exposure of sheep to sewage sludge chemicals disrupts sperm
      production in adulthood in a subset of animals.
AB  - Exposure to ubiquitous, environmental chemicals (ECs) has been hypothesized as a
      cause for declining male reproductive health. Understanding the long-term effects
      of EC exposure on reproductive health in humans requires animal models and
      exposure to 'real life', environmentally relevant, mixtures during development, a
      life stage of particular sensitivity to ECs. The aim of this study was to
      evaluate the effects of in utero and post-natal exposure to environmentally
      relevant levels of ECs, via sewage sludge application to pasture, on the adult
      male sheep testis. Hormones, liver concentrations of candidate ECs and Sertoli
      and germ cell numbers in testes of adult rams that were exposed to ECs in sewage
      sludge in utero, and until weaning via maternal exposure, and post-weaning via
      grazing pastures fertilized with sewage sludge, were quantified. Evaluated as a
      single group, exposure to sludge ECs was without significant effect on most
      parameters. However, a more detailed study revealed that 5 of 12 sludge-exposed
      rams exhibited major spermatogenic abnormalities. These consisted of major
      reductions in germ cell numbers per testis or per Sertoli cell and more Sertoli
      cell-only tubules, when compared with controls, which did not show any such
      changes. The sludge-related spermatogenic changes in the five affected animals
      were significantly different from controls (p < 0.001); Sertoli cell number was
      unaffected. Hormone profiles and liver candidate EC concentrations were not
      measurably affected by exposure. We conclude that developmental exposure of male
      sheep to real-world mixtures of ECs can result in major reduction in germ cell
      numbers, indicative of impaired sperm production, in a proportion of exposed
      males. The individual-specific effects are presumed to reflect EC effects on a
      heterogeneous population in which some individuals may be more susceptible to
      adverse EC effects. Such effects of EC exposure in humans could have adverse
      consequences for sperm counts and fertility in some exposed males.

PMID- 22150467
TI  - Farewell, 'renegade researcher': your voice will be missed.

PMID- 22150466
TI  - Clinical decision support systems in the care of inpatients with diabetes in non
      critical care setting: systematic review.
AB  - BACKGROUND: Computerized clinical decision support systems have been claimed to
      reduce prescription errors and improve patient care. They may play an important
      role in the care of hospitalized patients with diabetes. AIM: To collate evidence
      for the use of clinical decision support systems in improving the care of
      hospitalized patients with diabetes in a non-critical care setting and to assess
      their effectiveness. METHODS: We searched four databases from 1980 to 2010
      without language restrictions. All types of studies other than case reports were
      included. Data extraction and quality assessment were carried out based on the
      Centre for Review and Dissemination guidance. A narrative synthesis was
      conducted. RESULTS: Fourteen studies met the inclusion criteria, including two
      cluster randomized controlled trials, eight before-and-after studies and four
      other descriptive studies. Generally, the quality of the studies was not very
      high. Nine out of 10 studies reported reduction in mean blood glucose or similar
      measures (patient-day-weighted mean blood glucose) during inpatient stay. The
      reduction using computerized physician order entry system in patient-day-weighted
      mean blood glucose ranged from 0.6 to 0.8 mmol/l (10.8-15.6 mg/dl). Other
      beneficial effects during inpatient stay included reduced use of sliding scale
      insulin and greater use of basal-bolus insulin regimen. Only one study found a
      significant increase in hypoglycaemic events. CONCLUSIONS: Clinical decision
      support systems have been used, often as part of a complex programme, to improve
      the care of hospitalized patients with diabetes. There is some evidence that they
      may have a beneficial effect, but this needs further confirmation.

PMID- 22150468
TI  - Eggs ultrastructure and early development of Franciscodoras marmoratus (Pisces:
      Doradidae).
AB  - This study presents, for the first time, information on the eggs and early
      development of Franciscodoras marmoratus, fish of Sao Francisco river, Brazil. To
      analyse the egg ultrastructure and morphological events of embryogenesis, a total
      of 36 F. marmoratus specimens (18 males and 18 females) were captured and
      subjected to spawning induction. Gametes were collected by manual extrusion, and
      fertilization was conducted using the dry method. After fertilization, eggs were
      kept in incubators with water temperature of 24 degrees C. The embryonic
      development was monitored using a stereomicroscope until hatching. There was a
      67% positive response to hypophysation by the females and the fertilization rate
      was 73.8 +/- 6.2%. The oocytes are discoid, yellow, adhesive and covered by a
      thick jelly coat. Under the electron scanning microscope, the oocytes presented a
      surface with pore canals and funnel-shaped micropyle with a smooth vestibule.
      Recently extruded oocytes had a mean diameter of 1.27 +/- 0.4 mm and after
      hydration was 1.91 +/- 0.05 mm. The jelly coat was 0.34 +/- 0.03 mm thickness,
      and the perivitelline space was 0.19 +/- 0.04 mm. Eight phases of the embryonic
      development were identified, and embryogenesis was completed at 47 h after
      fertilization, at 24 degrees C water temperature. The recently hatched larvae had
      2.76 +/- 0.57 mm of total length. These results provide useful information for
      the successful breeding and reproductive strategies of fishes.

PMID- 22150469
TI  - Characteristics of American Psychological Association Division 40 (clinical
      neuropsychology) Fellows.
AB  - Fellow status is an honor bestowed on American Psychological Association (APA)
      members who have made unusual and outstanding contributions to the field of
      psychology that have had a national impact. Thus far no studies have examined the
      characteristics of the individuals who have received this honor. This study
      examined publicly available data for 157 Division 40 Fellows. Fellows comprise
      3.7% of the 4273 members of the division compared to 5.7% of the entire APA
      membership. Fellows are predominantly male (73%). All but two fellows had earned
      a Ph.D. with the average time since granting of the doctoral degree of 17.1 +/- 6
      years (median=16 years) with a range of 7-40 years post-degree. Slightly over
      half of the fellows hold board certification (53%) in the American Board of
      Professional Psychology. The largest group of fellows reports their primary
      employment currently as a university-affiliated medical setting (48%). These data
      serve to characterize current Division 40 Fellows for the field of
      neuropsychology and may provide useful information to assist prospective fellow
      applicants.

PMID- 22150470
TI  - Using bioluminescent assays as quantitative cell-based and biochemical
      biosensors.

PMID- 22150471
TI  - Combinatorial Chemistry & High Throughput Screening. Meet the guest editor.

PMID- 22150472
TI  - Efficacy of occupant-collected dust samples in the evaluation of residential
      allergen and fungal levels.
AB  - This study evaluated the ability of a resident to evaluate their home for
      allergens and mold using a settled dust test kit compared with evaluation and
      collection of settled dust by an industrial hygienist. Forty-three home residents
      were provided with a kit containing written instructions and a vacuum cleaner
      attachment for collecting a settled dust sample. Within 2 weeks of receiving the
      occupant-collected sample, an industrial hygienist evaluated these homes,
      including a visual inspection, collection of settled dust, and collection of
      spore trap samples. Settled dust samples were analyzed for major dog, cat, dust
      mite, and cockroach allergens using immunoassay methods, and for mold spore
      equivalents using quantitative polymerase chain reaction methods for the 13 mold
      species or species groups comprising the American Relative Moldiness Index
      (ARMI). Allergen concentrations and ARMIs were compared between the resident- and
      industrial hygienist-collected samples. Linear regression between the two sets of
      samples showed strong correlations for dog allergen (r(2) = 0.92) and cat
      allergen (r(2) = 0.90). Correlations for dust mite (r(2) = 0.57) and cockroach
      allergens (r(2) = 0.22) were lower, likely due to most samples being near the
      limit of detection. ARMIs were highly correlated (r(2) = 0.68) and were in
      categorical (high, medium, or low) agreement for 76% of residences. These results
      show that residents can reliably follow directions and collect settled dust
      samples, providing an efficient method to remotely screen homes for elevated
      allergen levels and to identify homes with a potential mold or moisture problem
      that may need further evaluation.

PMID- 22150473
TI  - Critically ill cancer patients in the intensive care unit: short-term outcome and
      1-year mortality.
AB  - BACKGROUND: The short-term survival of critically ill patients with cancer has
      improved over time. Studies providing long-term outcome for these patients are
      scarce. METHODS: We prospectively analyzed outcomes and rates of successful
      discharge of 111 consecutive critically ill cancer patients admitted to intensive
      care unit (ICU) in 2008 and identified factors influencing these results.
      RESULTS: ICU mortality was 32% and hospital mortality was 41%. None of the
      characteristics of the malignancy nor age or neutropenia were significantly
      different between survivors and others. Two variables were independently
      associated with ICU mortality: high Logistic Organ Dysfunction score on day 7 and
      a diagnosis of viral infection and/or reactivation. The 1-year mortality rate for
      ICU survivors was 58% and was significantly lower in patients with a diagnosis of
      acute leukemia or multiple myeloma. CONCLUSION: Organ failure scores on day 7 can
      predict outcome for cancer patients in the ICU. Viral infection and reactivation
      appear to worsen the prognosis. One-year mortality rate is high and depends on
      the malignancy.

PMID- 22150474
TI  - Early graphic representations of groundwater nitrate concentrations.

PMID- 22150476
TI  - Role of temporal resolution in selection of the appropriate strain technique for
      evaluation of subclinical myocardial dysfunction.
AB  - OBJECTIVE: To assess the effects of frame and volume rate on the concordance
      between two-dimensional speckle tracking strain (2DS) and three-dimensional
      speckle tracking strain (3DS), and between 2DS and triplane imaging of speckle
      tracking (Tri-P). METHODS: Global longitudinal strains (GLSs) derived from 2DS,
      3DS, and Tri-P were compared among 142 prospectively recruited patients who
      underwent evaluation of subclinical left ventricle (LV) function. RESULTS:
      Feasibility to obtain GLS of 3DS was significantly higher than that of Tri-P (76%
      vs. 47%, P < 0.001). The correlation between 2DS and 3DS was only modest (r =
      0.47) whereas that of 2DS and Tri-P was better (r = 0.67). The difference in
      frame/volume rate between two methods also affected their correlation. A volume
      rate between 34 and 50 volumes/sec had the highest correlation between 2DS and
      3DS (r = 0.72). The correlation between 2DS and Tri-P was better with a
      difference in frame-rate <=20 per second than with a difference >20 per second.
      Likewise, there was a better correlation between 2DS and 3DS when the difference
      between 2D frame rate and 3D volume rate was <=40 per second, compared to when it
      was >40 per second. These associations differed from segment to segment and the
      apical segments had the highest correlation and the basal the lowest.
      CONCLUSIONS: The feasibility of each means of strain calculation showed important
      differences, with 2DS being the most attainable. Strain values were not
      interchangeable among 2DS, Tri-P, and 3DS. Importantly, poor correlations seemed
      to be driven by differences in acquisition rate. Currently, 2DS offers the most
      robust measurement of subclinical myocardial dysfunction. 

PMID- 22150475
TI  - Overweight and obesity predict time to periodontal disease progression in men.
AB  - AIMS: To examine whether overweight and obesity indicators - body mass index
      (BMI), waist circumference (WC), and WC-to-height ratio - predict progression of
      periodontal disease in men. MATERIAL AND METHODS: Participants were 1038
      medically healthy, non-Hispanic, white males in the VA Dental Longitudinal Study
      who were monitored with triennial oral and medical examinations between 1969 and
      1996. Periodontal disease progression in an individual was defined as having two
      or more teeth advance to levels of alveolar bone loss >=40%, probing pocket depth
      >=5 mm, or clinical attachment loss >=5 mm after baseline. Extended Cox
      regression analyses estimated hazards of experiencing periodontal disease
      progression events due to overweight/obesity status, controlling for age,
      smoking, education, diabetes, recent periodontal treatment, recent prophylaxis,
      and number of filled/decayed surfaces. RESULTS: Body mass index and WC-to-height
      ratio were significantly associated with hazards of experiencing periodontal
      disease progression events regardless of periodontal disease indicator. Adjusted
      hazard ratios for periodontal disease progression were 41-72% higher in obese men
      (BMI >=30 kg/m(2)) relative to men with both normal weight and WC-to-height ratio
      (<=50%). CONCLUSION: Both overall obesity and central adiposity are associated
      with an increased hazards of periodontal disease progression events in men.

PMID- 22150477
TI  - A two-year investigation towards an effective quality control of incoming
      potatoes as an acrylamide mitigation strategy in french fries.
AB  - The current entrance quality control used in the french fries industry is done
      based on colour evaluation with a United States Department of Agriculture/Munsell
      colour chart (after a short frying test, typically 180 degrees C for 3 min). On
      the basis of a study carried out during two consecutive potato storage seasons,
      the possibility of a more effective entrance control of the raw potato tubers in
      order to identify batches of potatoes prone to acrylamide formation was
      evaluated. The current entrance control was compared to two other colour
      evaluation methods (CIE L*a*b* colour parameters and a process-specific Agtron
      analyser) and to reducing sugar content determination. Seasonal variability did
      not affect the slopes of the linear correlation models, for most of the
      parameters studied. The determination of colour formation measured by the Agtron
      methodology and reducing sugar content allowed a better identification of batches
      of potatoes prone to acrylamide formation compared with the current entrance
      control. Different scenarios represented by decision trees for quality control
      measures for incoming potatoes were evaluated while considering the investigation
      value of 600 ug kg-1 for french fries recently prescribed by the European
      Commission. Samples were categorised based on predictions of threshold values and
      acrylamide levels in the final product.

PMID- 22150478
TI  - Eruptive milium-like syringoma showing eccrine duct origin of milia.

PMID- 22150479
TI  - Acute down-regulation of adenosine A(1)  receptor activity in status epilepticus.
AB  - PURPOSE: Status epilepticus (SE) remains a potentially devastating condition that
      quickly becomes refractory to antiepileptic drug treatment and arises as a result
      of a failure of the brain's endogenous antiepileptic mechanisms. Understanding
      these mechanisms and how they are disrupted in SE is necessary in order to
      identify novel therapeutic approaches. Adenosine is considered an endogenous
      anticonvulsant. Extracellular concentrations increase coinciding with seizure
      termination; activation of A(1) receptors (A(1)Rs) reduces seizure-induced damage
      and epileptiform activity. The present study examines the effectiveness of focal
      drug delivery in a model of limbic SE that closely resembles the human condition
      and describes, for the first time, alterations in A(1)R signaling during
      prolonged seizures that may contribute to the progression from self-terminating
      seizures to self-sustaining SE (SSSE). METHODS: We developed a rat perforant path
      stimulation model in which 50% of rats develop SSSE and tested whether modulation
      of A(1)Rs influenced SSSE development when drugs were infused to the dentate
      gyrus. We further determined the ability of A(1)Rs to modulate perforant path to
      granule cell transmission in hippocampal slices taken from sham-operated control
      and post-SE animals. KEY FINDINGS: Adenosine (3 MUM) and the A(1)R-selective
      agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA; 10 MUM) reduced the severity of
      SSSE as measured by spike count, electroencephalography power and behavioral
      seizure score. In addition, CCPA suppressed the progression to SSSE.
      Surprisingly, the A(1)R-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine
      (DPCPX; 1 MUm) had no effect on the severity of or progression to SSSE,
      suggesting a lack of intrinsic A(1)R activation. Immunohistochemistry revealed no
      alterations in total A(1)R expression. However, we observed a marked down
      regulation of A(1)R modulation of neurotransmission in vitro, indicating acute
      A(1)R desensitization. SIGNIFICANCE: These findings indicate that A(1)R
      activation can prevent the progression to SE and suggest that reduced A(1)R
      signaling promotes the transition of seizures to SSSE.

PMID- 22150481
TI  - Fractured neck of femur: guidelines and beyond.

PMID- 22150482
TI  - Pharmacokinetics and pharmacodynamics--is there anything new?

PMID- 22150483
TI  - Complement takes its Toll: an inflammatory crosstalk between Toll-like receptors
      and the receptors for the complement anaphylatoxin C5a.
AB  - The innate immune system is responsible for a rapid inflammatory response to
      pathogens that is essential for the clearance of infections. Although this
      response is vital, it is nonetheless potentially harmful, and dysregulated
      inflammation is a feature of many disease states. Thus, the mechanisms that
      regulate the release of soluble mediators of inflammation are an active focus of
      investigation. The activation by infections of two key components of the innate
      immune system, the Toll-like receptors (TLRs) and complement, leading to the
      release of soluble mediators of inflammation, is critical to microbial killing
      and clearance. Both TLRs and complement are independently capable of triggering
      pro-inflammatory responses, but their synergistic interaction resulting from a
      substantial crosstalk markedly amplifies those responses and may contribute to
      the pathophysiology of diseases such as sepsis.

PMID- 22150484
TI  - Confusion due to site of tracheal tube size marking.

PMID- 22150485
TI  - Specialty-appointed professors of anaesthesia: a solution to the problem of
      marginalisation of our specialty in national reports and enquiries.

PMID- 22150486
TI  - Safe central venous cannulation.

PMID- 22150488
TI  - Acoustic shadowing from neuraxial bone.

PMID- 22150490
TI  - Apnea and mydriasis after postoperative tramadol administration: an unusual
      complication and possible underlying mechanisms.

PMID- 22150491
TI  - Mandibular nerve block for peri-operative pain relief using a peripheral nerve
      stimulator.

PMID- 22150492
TI  - The sweetie tube and a paediatric difficult airway.

PMID- 22150493
TI  - The i-scoop: a laryngoscope with new perspectives.

PMID- 22150494
TI  - Large retroperitoneal haematoma: an unexpected complication of ilioinguinal nerve
      block for inguinal hernia repair.

PMID- 22150495
TI  - Anaphylaxis to dye during breast surgery.

PMID- 22150496
TI  - Cardiovascular intubation responses with the Airway Scope(r) and the Macintosh
      laryngoscope.

PMID- 22150497
TI  - Failure of intravenous cannula one-way valve.

PMID- 22150499
TI  - Bougie regulation; is it stiff enough?

PMID- 22150500
TI  - Latex containing pre-filled syringes.

PMID- 22150501
TI  - Management of proximal femoral fractures 2011: Association of Anaesthetists of
      Great Britain and Ireland.
AB  - There should be protocol-driven, fast-track admission of patients with hip
      fractures through the emergency department. Patients with hip fractures require
      multidisciplinary care, led by orthogeriatricians. Surgery is the best analgesic
      for hip fractures. Surgical repair of hip fractures should occur within 48 hours
      of hospital admission. Surgery and anaesthesia must be undertaken by
      appropriately experienced surgeons and anaesthetists. There must be high-quality
      communication between clinicians and allied health professionals. Early
      mobilisation is a key part of the management of patients with hip fractures. Pre
      operative management should include consideration of planning for discharge from
      hospital. Measures should be taken to prevent secondary falls. 10. Continuous
      audit and targeted research is required in order to inform and improve the
      management of patients with hip fracture.

PMID- 22150502
TI  - The effects of sevoflurane anesthesia and cardiopulmonary bypass on renal
      function in cyanotic and acyanotic children undergoing cardiac surgery.
AB  - BACKGROUND: There are few data on the effects of anesthesia and cardiopulmonary
      bypass (CPB) on perioperative renal function in children with cyanotic congenital
      heart disease undergoing open heart surgery. This study aims to investigate the
      perioperative renal function in cyanotic versus acyanotic children undergoing
      sevoflurane anesthesia for open heart surgery. METHODS: After receiving ethical
      committee approval, 12 acyanotic patients (preoperative oxygen saturation: SaO(2)
      > 85%) and 12 cyanotic children (SaO(2) < 85%) were included. Sevoflurane was
      administered at concentration levels of 2% before CPB and 1-2% during CPB after
      standard anesthesia induction. Inorganic fluoride, electrolytes, creatinine, urea
      nitrogen in serum and urine samples, and N-acetyl-beta-d-glucosaminidase (NAG) in
      urine samples were measured before induction, before CPB, during CPB, after CPB,
      at the end of surgery, and at 24th h postoperatively. RESULTS: The levels of
      serum uric acid levels were higher in the cyanotic group (p < 0.05). There were
      no differences in the levels of serum creatinine and urine creatinine, urea
      nitrogen, and electrolytes between the two groups. Serum inorganic fluoride
      levels were always higher in the acyanotic group than in the cyanotic group, but
      these differences between the groups reached statistical significance at two
      measurement times (before CPB and end of surgery) (p < 0.05). Urinary inorganic
      fluoride levels increased with time in both groups. Although urinary NAG
      increased significantly after the CPB in the cyanotic group, the differences
      between the two groups did not reach statistical significance. CONCLUSIONS: We
      have concluded that renal function was not affected during open heart surgery
      with sevoflurane anesthesia, in both cyanotic and acyanotic children.

PMID- 22150504
TI  - Caudal mediastinal paraesophageal abscesses in 7 dogs.
AB  - OBJECTIVE: To report clinical, imaging, and surgical findings associated with
      caudal mediastinal paraesophageal abscesses (CMPA) in dogs and outcome after
      surgical treatment. STUDY DESIGN: Case series. ANIMALS: Dogs (n = 7) with CMPA.
      METHODS: Medical records (April 2005-January 2010) were reviewed for dogs with
      CMPA treated surgically. Retrieved data were signalment, history, clinical
      findings, diagnostic investigations, surgical findings, surgical procedures
      performed, and postoperative recovery. Long-term follow-up information was
      obtained by telephone questionnaire of owners and referring veterinarians.
      RESULTS: Median sternotomy (5 dogs) or lateral thoracotomy (2 dogs) was used for
      access to CMPA, which were drained and partially debrided surgically. In 5 dogs,
      omentalization of the abscess cavity was performed through a diaphragmatic
      incision. Foreign material was not identified within any abscess. All dogs were
      discharged from the hospital and had full recovery. CONCLUSIONS: CMPA should be
      suspected when there is regurgitation and pyrexia associated with a mass or
      enlargement in the caudal mediastinum. CMPA appears to have a good prognosis
      after aggressive surgical therapy.

PMID- 22150506
TI  - Gestational diabetes mellitus in Europe: prevalence, current screening practice
      and barriers to screening. A review.
AB  - BACKGROUND: Gestational diabetes mellitus is a potentially serious condition that
      affects many pregnancies and its prevalence is increasing. Evidence suggests
      early detection and treatment improves outcomes, but this is hampered by
      continued disagreement and inconsistency regarding many aspects of its diagnosis.
      METHODS: The Vitamin D and Lifestyle Intervention for Gestational Diabetes
      Mellitus Prevention (DALI) research programme aims to promote pan-European
      standards in the detection and diagnosis of gestational diabetes and to develop
      effective preventive interventions. To provide an overview of the context within
      which the programme will be conducted and its findings interpreted, systematic
      searching and narrative synthesis have been used to identify and review the best
      available European evidence relating to the prevalence of gestational diabetes,
      current screening practices and barriers to screening. RESULTS: Prevalence is
      most often reported as 2-6% of pregnancies. Prevalence may be lower towards the
      Northern Atlantic seaboard of Europe and higher in the Southern Mediterranean
      seaboard. Screening practice and policy is inconsistent across Europe, hampered
      by lack of consensus on testing methods, diagnostic glycaemic thresholds and the
      value of routine screening. Poor clinician awareness of gestational diabetes, its
      diagnosis and local clinical guidelines further undermine detection of
      gestational diabetes. CONCLUSIONS: Europe-wide agreement on screening approaches
      and diagnostic standards for gestational diabetes could lead to better detection
      and treatment, improved outcomes for women and children and a strengthened
      evidence base. There is an urgent need for well-designed research that can inform
      decisions on best practice in gestational diabetes mellitus screening and
      diagnosis.

PMID- 22150507
TI  - Modelling the concentration-time relationship in milk from cattle administered an
      intramammary drug.
AB  - Antimicrobial drugs are often infused directly through the streak canal into the
      bovine udder for the treatment or prevention of mastitis. These infusions have
      two major problems: drug residues in milk and variable antimicrobial efficacy.
      Both problems are influenced by the pharmacokinetics of intramammary delivery and
      elimination of drugs. This pharmacokinetics does not conform to the assumptions
      of traditional first-order mamillary pharmacokinetic models. To help understand
      drug delivery into and elimination from the udder, a new approach to
      pharmacokinetic modelling of the udder is proposed. This new model was used to
      predict the movement of drug within the udder and the concentrations of drug
      achieved within physiological compartments of the udder. These predictions were
      examined using computer modelling. The model was evaluated using data from in
      vivo intramammary infusion of cefuroxime. The model predicts that changes in
      milking efficiency (residual volume), milk productivity and milking frequency can
      impact both the drug residue persistence and the time that milk drug
      concentrations exceed the minimum inhibitory concentrations for pathogens. The
      model provides a new tool for future evaluation of intramammary dosing studies.

PMID- 22150508
TI  - Effects of the triple monoamine uptake inhibitor DOV 102,677 on alcohol-motivated
      responding and antidepressant activity in alcohol-preferring (P) rats.
AB  - BACKGROUND:   Concurrent inhibitors of dopamine, norepinephrine, and serotonin
      uptake have been proposed as novel antidepressants. Given the high comorbidity
      between alcoholism and depression, we evaluated the activity of DOV 102,677 (DOV)
      on alcohol-maintained responding and performance in the forced swim test (FST), a
      model of antidepressant (AD) activity, using alcohol-preferring (P) rats.
      METHODS:   Following training to lever press for either alcohol (10% v/v) or
      sucrose (3, 2%, w/v) on a fixed-ratio 4 (FR4) schedule, DOV (1.56 to 50 mg/kg;
      PO) was given 25 minutes or 24 hours prior to evaluation. The effects of DOV
      (12.5 to 50 mg/kg; PO) in the FST were evaluated 25 minutes posttreatment.
      RESULTS:   DOV (6.25 to 50 mg/kg) dose-dependently reduced alcohol-maintained
      responding by 59 to 88% at 25 minutes posttreatment, without significantly
      altering sucrose responding. The reduction in alcohol responding (44% at 50
      mg/kg) was sustained for up to 120 hours after a single dose. Administration of a
      single dose of DOV (25, 50 mg/kg) 24 hours before testing suppressed alcohol
      responding for 48 hours by 59 to 62%. DOV (12.5 to 50 mg/kg) also dose
      dependently reduced immobility of P rats in the FST. CONCLUSIONS:   DOV produces
      both prolonged and selective reductions of alcohol-motivated behaviors in P rats.
      The elimination kinetics of DOV suggests that its long duration of action may be
      due to an active metabolite. DOV also produced robust AD-like effects in P rats.
      We propose that DOV may be useful in treating comorbid alcoholism and depression
      in humans.

PMID- 22150509
TI  - Evaluation of thermal inactivation of Escherichia coli using microelectrode ion
      flux measurements with osmotic stress.
AB  - AIMS: To elucidate the potential use of microelectrode ion flux measurements to
      evaluate bacterial responses to heat treatment. METHODS AND RESULTS: Escherichia
      coli K12 was used as a test bacterium to determine whether various heat
      treatments (55-70 degrees C for 15 min) affected net ion flux across E. coli cell
      membranes using the MIFETM system to measure net K(+) fluxes. No difference in
      K(+) fluxes was observed before and after heat treatments regardless of the
      magnitude of the treatment. Applying hyperosmotic stress (3% NaCl w/v) during
      flux measurement led to a net K(+) loss from the heat-treated E.coli cells below
      65 degrees C as well as from nonheated cells. In contrast, with E. coli cells
      treated at and above 65 degrees C, hyperosmotic stress disrupted the pattern of
      K(+) flux observed at lower temperatures and resulted in large flux noise with
      random scatter. This phenomenon was particularly apparent above 70 degrees C.
      Although E. coli cells lost the potential to recover and grow at and above 62
      degrees C, K(+) flux disruption was not clearly observed until 68 degrees C was
      reached. CONCLUSIONS: No changes in net K(+) flux from heat-stressed E. coli
      cells were observed directly as a result of thermal treatments. However,
      regardless of the magnitude of heat treatment above 55 degrees C, loss of
      viability indicated by enrichment culture correlated with disrupted K(+) fluxes
      when previously heated cells were further challenged by imposing hyperosmotic
      stress during flux measurement. This two-stage process enabled evaluation of the
      lethality of heat-treated bacterial cells within 2 h and may be an alternative
      and more rapid method to confirm the lethality of heat treatment. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The ability to confirm the lethality of thermal
      treatments and to specify minimal time/temperature combinations by a nonculture
      dependent test offers an alternative system to culture-based methods.

PMID- 22150510
TI  - Comparing the effects of weathering and microbial degradation on gasoline using
      principal components analysis.
AB  - Ignitable liquid residues recovered from a fire scene will often show signs of
      weathering as a result of exposure to the heat of the fire. In addition, when the
      substrate is rich in organic matter, both weathering and microbial degradation
      may be observed. In this study, 20 MUL aliquots of fresh gasoline samples were
      intentionally weathered and also subjected to microbial degradation in potting
      soil. These samples were then analyzed using a passive adsorption-elution
      recovery method and gas chromatography/mass spectrometry. Peak areas from
      compounds of interest were normalized and autoscaled and then subjected to
      principal components analysis. This analysis showed that while lower boiling
      compounds are subject to weathering, a different set of compounds are subject to
      microbial degradation. Of the compounds studied, heptane, octane, toluene, and
      ethylbenzene were the most vulnerable to both weathering and microbial
      degradation. In contrast, 1,3,5-trimethylbenzene and 2-ethyltoluene were the most
      resistant to both phenomena.

PMID- 22150511
TI  - The informed society: an analysis of the public's information-seeking behavior
      regarding coastal flood risks.
AB  - Recent flood risk management puts an increasing emphasis on the public's risk
      perception and its preferences. It is now widely recognized that a better
      knowledge of the public's awareness and concern about risks is of vital
      importance to outline effective risk communication strategies. Models such as
      Risk Information Seeking and Processing address this evolution by considering the
      public's needs and its information-seeking behavior with regard to risk
      information. This study builds upon earlier information-seeking models and
      focuses on the empirical relationships between information-seeking behavior and
      the constructs of risk perception, perceived hazard knowledge, response efficacy,
      and information need in the context of coastal flood risks. Specific focus is
      given to the mediating role of information need in the model and to the
      differences in information-seeking behavior between permanent and temporary
      residents. By means of a structured on-line questionnaire, a cross-sectional
      survey was carried out in the city of Ostend, one of the most vulnerable places
      to coastal flooding on the Belgian coast. Three hundred thirteen respondents
      participated in the survey. Path analysis reveals that information need does not
      act as a mediator in contrast to risk perception and perceived knowledge. In
      addition, it is shown that risk perception and perceived hazard knowledge are
      higher for permanent than temporary residents, leading to increased information
      seeking behavior among the former group. Implications for risk communication are
      discussed.

PMID- 22150512
TI  - Patterns of spatio-temporal distribution of winter chronic photoinhibition in
      leaves of three evergreen Mediterranean species with contrasting acclimation
      responses.
AB  - High irradiance and relatively low temperature, which characterize Mediterranean
      winters, cause chilling stress in plants. Downregulation of photosynthetic
      efficiency is a mechanism that allows plants to survive these conditions. This
      study aims to address whether this process shows a regular spatial pattern across
      leaf surface or not. Three species (Buxus sempervirens, Cistus albidus and
      Arctostaphylos uva-ursi) with contrasting responses to winter stress were
      studied. During 7 days, macro and micro Fv/Fm spatial patterns were monitored by
      the use of chlorophyll fluorescence imaging techniques. In the field, the
      strongest photoinhibition was found in B. sempervirens, while there was almost no
      chronic photoinhibition in C. albidus. In leaves of the first species, Fv/Fm
      decreased from base to tip while in C. albidus it was uniform over the leaf
      lamina. An intermediate behavior is shown by A. uva-ursi leaves. Spatial
      heterogeneity distribution of Fv/Fm was found inside the leaves, resulting in
      greater Fv/Fm values in the inner layers than in the outer ones. Neither
      xanthophyll-linked downregulation of Fv/Fm nor protein remobilization were the
      reasons for such spatial patterns since pigment composition and nitrogen content
      did not reveal tip-base differences. During recovery from winter, photoinhibition
      changes occurred in Fv/Fm, pigments and chloroplast ultrastructure. This work
      shows for the first time that irrespective of physiological mechanisms
      responsible for development of winter photoinhibition, there is an acclimation
      response with strong spatio-temporal variability at leaf level in some species.
      This observation should be taken into account when modeling or scaling up
      photosynthetic responses.

PMID- 22150513
TI  - Folded functional lipid-poor apolipoprotein A-I obtained by heating of high
      density lipoproteins: relevance to high-density lipoprotein biogenesis.
AB  - HDL (high-density lipoproteins) remove cell cholesterol and protect from
      atherosclerosis. The major HDL protein is apoA-I (apolipoprotein A-I). Most
      plasma apoA-I circulates in lipoproteins, yet ~5% forms monomeric lipid-poor/free
      species. This metabolically active species is a primary cholesterol acceptor and
      is central to HDL biogenesis. Structural properties of lipid-poor apoA-I are
      unclear due to difficulties in isolating this transient species. We used thermal
      denaturation of human HDL to produce lipid-poor apoA-I. Analysis of the isolated
      lipid-poor fraction showed a protein/lipid weight ratio of 3:1, with apoA-I, PC
      (phosphatidylcholine) and CE (cholesterol ester) at approximate molar ratios of
      1:8:1. Compared with lipid-free apoA-I, lipid-poor apoA-I showed slightly altered
      secondary structure and aromatic packing, reduced thermodynamic stability, lower
      self-associating propensity, increased adsorption to phospholipid surface and
      comparable ability to remodel phospholipids and form reconstituted HDL. Lipid
      poor apoA-I can be formed by heating of either plasma or reconstituted HDL. We
      propose the first structural model of lipid-poor apoA-I which corroborates its
      distinct biophysical properties and postulates the lipid-induced ordering of the
      labile C-terminal region. In summary, HDL heating produces folded functional
      monomolecular lipid-poor apoA-I that is distinct from lipid-free apoA-I.
      Increased adsorption to phospholipid surface and reduced C-terminal disorder may
      help direct lipid-poor apoA-I towards HDL biogenesis.

PMID- 22150514
TI  - Medication management and neuropsychological performance in Parkinson's disease.
AB  - Medication non-adherence is associated with chronic disease and complex
      medication schedules, and Parkinson's disease (PD) patients also frequently have
      cognitive impairments that may interfere with effective medication management.
      The current study quantitatively assessed the medication management skills of PD
      patients and probed the neurocognitive underpinnings and clinical correlates of
      this skill. A total of 26 men with PD completed a neuropsychological battery and
      a modified version of the Hopkins Medication Schedule (HMS), a standard test of a
      person's ability to understand and implement a routine prescription medication.
      Estimated adherence rates from performance on the HMS were low. Memory, executive
      functioning, and processing speed were strongly related to different components
      of the HMS. A range of neuropsychological abilities is associated with the
      ability to understand and implement a medication schedule and pillbox in
      individuals with PD.

PMID- 22150516
TI  - Origins and originators: lesbian couples negotiating parental identities and
      sperm donor conception.
AB  - Donor conception challenges conventional kinship idioms: the involvement of a
      gamete donor culturally raises questions about parentage and also the meaning of
      genetic heritage. Although there is now a growing body of literature exploring
      how people resorting to donor conception negotiate kinship and connectedness,
      this predominantly focuses on heterosexual couples. Little is yet known about how
      lesbian couples navigate these processes. This paper builds on a qualitative
      interview study comprising 25 lesbian couples in England and Wales with
      experiences of pursuing donor conception in the context of their couple
      relationship to explore how these couples negotiate the contribution of the
      donor. It explores how couples negotiate meanings of parenthood, genetic origins
      and the bodily process of conception. The paper argues that lesbian couples
      negotiate parental identities, biogenetic relationships and also the meaning of
      conception by disassembling and reassembling the meaning of kinship, parenthood,
      creation, origin and originator. Findings suggest that lesbian couples weave
      together old and new understandings of relatedness in complex patterns and that
      this enables them to assert authority as parents.

PMID- 22150515
TI  - Evaluating a persistent nuisance odor in an office building.

PMID- 22150517
TI  - The application of ecohydrological groundwater indicators to hydrogeological
      conceptual models.
AB  - This article reviews the application of ecohydrological indicators to
      hydrogeological conceptual models for earth-scientists with little or no
      botanical training. Ecohydrological indicators are plants whose presence or
      morphology can provide data about the hydrogeological setting. By examining the
      literature from the fields of ecohydrology, hydrogeology, geobotany, and ecology,
      this article summarizes what is known about groundwater indicator plants, their
      potential for providing information about the aquifer, and how this data can be a
      cost-effective addition to hydrogeological conceptual models. We conclude that
      the distribution and morphology of ecohydrological groundwater indicator plants
      can be useful to hydrogeologists in certain circumstances. They are easiest to
      evaluate in arid and semiarid climates. Ecohydrological groundwater indicators
      can provide information about the absolute depth to the water table, patterns of
      groundwater fluctuation, and the mineralization of the aquifer. It is shown that
      an understanding of the meteorological conditions of a region is often necessary
      to accurately interpret groundwater indicator plants and that useful data is
      usually obtained by observing patterns of vegetation behavior rather than
      interpreting individual plants. The most serious limitations to applying this
      source of information to hydrogeological conceptual models are the limited data
      in the literature and the regional nature of many indicator plants. The physical
      and physiological indications of the plants exist, but little effort has been
      made to interpret them. This article concludes by outlining several potential
      lines of research that could further the usefulness of ecohydrological
      groundwater indicators to the hydrogeological community.

PMID- 22150518
TI  - Neurochemical properties of aquaporin 1-expressing sensory neurons from the ovine
      trigeminal ganglion.
AB  - Aims of the present study were to investigate the distribution and morphology of
      aquaporin 1-immunoreactive (AQP1-IR) neurons in the sensory ganglia of the sheep.
      Double immunohistochemical staining was applied to figure out whether substance P
      (SP), calcitonin gene-related peptide (CGRP) and galanin are present in AQP1
      bearing primary afferent neurons. The expression of AQP1 was present only in
      trigeminal ganglion, whereas in nodose ganglion, jugular ganglion as well as C(1)
      -C(7) dorsal root ganglia no presence of AQP1 was found. In trigeminal ganglion,
      15.4 +/- 2.3% of Hu C/D-IR neurons (pan-neuronal marker) showed the presence of
      AQP1. The vast majority of AQP1-IR trigeminal sensory neurons (approximately 69.6
      +/- 3.3%, n = 5) were classified as middle in size, 28.6 +/- 3.0% of AQP1-IR
      neurons were small and only 1.8 +/- 0.6% of AQP1-positive neurons were large in
      size. Amongst the population of AQP1-IR trigeminal neurons as many as 58.5 +/-
      3.9% were immunopositive to SP, 30.7 +/- 2.3% showed the presence of CGRP and
      10.9 +/- 0.2% coexpressed galanin. In trigeminal ganglion, SP-IR as well as CGRP
      IR (but not galanin-IR) nerve fibres were found in close neighbourhood of AQP1-IR
      neurons. It is concluded that AQP1 is present in certain neuronal subsets of the
      ovine trigeminal ganglion; however, the exact role of this water channel has to
      be elucidated.

PMID- 22150519
TI  - Evolving from clinical case reports to clinical case letters: a new direction for
      the Journal of Oral Implantology.

PMID- 22150522
TI  - Listening to infant distress vocalizations enhances effortful motor performance.

PMID- 22150523
TI  - 'Intense inner agitation': an overlooked side effect of droperidol.

PMID- 22150524
TI  - Impaired consciousness in epilepsy investigated by a prospective responsiveness
      in epilepsy scale (RES).
AB  - PURPOSE: Impaired consciousness in epileptic seizures has a major negative impact
      on patient quality of life. Prior work on epileptic unconsciousness has mainly
      used retrospective and nonstandardized methods. Our goal was to validate and to
      obtain initial data using a standardized prospective testing battery. METHODS:
      The responsiveness in epilepsy scale (RES) was used on 52 patients during
      continuous video-electroencephalography (EEG) monitoring. RES begins with higher
      level questions and commands, and switches adaptively to more basic sensorimotor
      responses depending on patient performance. RES continues after seizures and
      includes postictal memory testing. Scoring was conducted based on video review.
      KEY FINDINGS: Testing on standardized seizure simulations yielded good intrarater
      and interrater reliability. We captured 59 seizures from 18 patients (35% of
      participants) during 1,420 h of RES monitoring. RES impairment was greatest
      during and after tonic-clonic seizures, less in partial seizures, and minimal in
      auras and subclinical seizures. In partial seizures, ictal RES impairment was
      significantly greater if EEG changes were present. Maximum RES impairment (lowest
      ictal score) was also significantly correlated with long postictal recovery time,
      and poor postictal memory. SIGNIFICANCE: We found that prospective testing of
      responsiveness during seizures is feasible and reliable. RES impairment was
      related to EEG changes during seizures, as well as to postictal memory deficits
      and recovery time. With a larger patient sample it is hoped that this approach
      can identify brain networks underlying specific components of impaired
      consciousness in seizures. This may allow the development of improved treatments
      targeted at preventing dysfunction in these networks.

PMID- 22150525
TI  - Mapping biological to clinical phenotypes during the development (21 days) and
      resolution (21 days) of experimental gingivitis.
AB  - AIM: To characterize and map temporal changes in the biological and clinical
      phenotype during a 21-day experimental gingivitis study. MATERIALS AND METHODS:
      Experimental gingivitis was induced over 21 days in healthy human volunteers (n =
      56), after which normal brushing was resumed (resolution phase). Gingival and
      plaque indices were assessed. Gingival crevicular fluid was collected from four
      paired test and contra-lateral control sites in each volunteer during induction
      (Days 0, 7, 14 and 21) and resolution (Days 28 and 42) of experimental
      gingivitis. Fluid volumes were measured and a single analyte was quantified from
      each site-specific, 30s sample. Data were evaluated by analysis of repeated
      measurements and paired sample tests. RESULTS: Clinical indices and gingival
      crevicular fluid volumes at test sites increased from Day 0, peaking at Day 21
      (test/control differences all p < 0.0001) and decreased back to control levels by
      Day 28. Levels of four inflammatory markers showed similar patterns, with
      significant differences between test and control apparent at Day 7 (substance P,
      cathepsin G, interleukin-1beta, elastase: all p < 0.03) and peaking at Day 21
      (all p < 0.002). Levels of alpha-1-antitrypsin showed no pattern. CONCLUSIONS:
      Levels of substance P, cathepsin G, interleukin-1beta and neutrophil elastase act
      as objective biomarkers of gingival inflammation induction and resolution that
      typically precede phenotypical changes.

PMID- 22150529
TI  - Effects of load on the time course of attentional engagement, disengagement, and
      orienting in reading.
AB  - We examined how the frequency of the fixated word influences the spatiotemporal
      distribution of covert attention during reading. Participants discriminated gaze
      contingent probes that occurred with different spatial and temporal offsets from
      randomly chosen fixation points during reading. We found that attention was
      initially focused at fixation and that subsequent defocusing was slower when the
      fixated word was lower in frequency. Later in a fixation, attention oriented more
      towards the next saccadic target for high- than for low-frequency words. These
      results constitute the first report of the time course of the effect of load on
      attentional engagement and orienting in reading. They are discussed in the
      context of serial and parallel models of reading.

PMID- 22150528
TI  - Estimated morbidity and mortality in adolescents and young adults diagnosed with
      Type 2 diabetes mellitus.
AB  - AIMS: To estimate remaining life expectancy (RLE), quality-adjusted life
      expectancy (QALE), causes of death and lifetime cumulative incidence of
      microvascular/macrovascular complications of diabetes for youths diagnosed with
      Type 2 diabetes. METHODS: A Markov-like computer model simulated the life course
      for a hypothetical cohort of adolescents/young adults in the USA, aged 15-24
      years, newly diagnosed with Type 2 diabetes following either conventional or
      intensive treatment based on the UK Prospective Diabetes Study. Outcomes included
      RLE, discounted QALE in quality-adjusted life years (QALYs), cumulative incidence
      of microvascular/macrovascular complications and causes of death. RESULTS:
      Compared with a mean RLE of 58.6 years for a 20-year-old in the USA without
      diabetes, conventional treatment produced an average RLE of 43.09 years and 22.44
      discounted QALYs. Intensive treatment afforded an incremental 0.98 years and 0.44
      discounted QALYs. Intensive treatment led to lower lifetime cumulative incidence
      of all microvascular complications and lower mortality from microvascular
      complications (e.g. end-stage renal disease (ESRD) death 19.4% vs. 25.2%).
      Approximately 5% with both treatments had ESRD within 25 years. Lifetime
      cumulative incidence of coronary heart disease (CHD) increased with longer RLE
      and greater severity of CHD risk factors. Incorporating disutility (loss in
      health-related quality of life) of intensive treatment resulted in net loss of
      QALYs. CONCLUSIONS: Adolescents/young adults with Type 2 diabetes lose
      approximately 15 years from average RLE and may experience severe, chronic
      complications of Type 2 diabetes by their 40s. The net clinical benefit of
      intensive treatment may be sensitive to preferences for treatment. A
      comprehensive management plan that includes early and aggressive control of
      cardiovascular risk factors is likely needed to reduce lifetime risk of CHD.

PMID- 22150526
TI  - Activation of mu opioid receptors in the striatum differentially augments
      methamphetamine-induced gene expression and enhances stereotypic behavior.
AB  - Mu opioid receptors are densely expressed in the patch compartment of striatum
      and contribute to methamphetamine-induced patch-enhanced gene expression and
      stereotypy. To further elucidate the role of mu opioid receptor activation in
      these phenomena, we examined whether activation of mu opioid receptors would
      enhance methamphetamine-induced stereotypy and prodynorphin, c-fos, arc and
      zif/268 expression in the patch and/or matrix compartments of striatum, as well
      as the impact of mu opioid receptor activation on the relationship between patch
      enhanced gene expression and stereotypy. Male Sprague-Dawley rats were
      intrastriatally infused with d-Ala(2)-N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO; 1
      MUg/MUL), treated with methamphetamine (0.5 mg/kg) and killed at 45 min or 2 h
      later. DAMGO augmented methamphetamine-induced zif/268 mRNA expression in the
      patch and matrix compartments, while prodynorphin expression was increased in the
      dorsolateral patch compartment. DAMGO pre-treatment did not affect
      methamphetamine-induced arc and c-fos expression. DAMGO enhanced methamphetamine
      induced stereotypy and resulted in greater patch versus matrix expression of
      prodynorphin in the dorsolateral striatum, leading to a negative correlation
      between the two. These findings indicate that mu opioid receptors contribute to
      methamphetamine-induced stereotypy, but can differentially influence the genomic
      responses to methamphetamine. These data also suggest that prodynorphin may
      offset the overstimulation of striatal neurons by methamphetamine.

PMID- 22150530
TI  - Residue depletion of albendazole and its metabolites in aquacultured yellow perch
      (Perca flavescens).
AB  - Metabolism and residue depletion studies are conducted to determine the marker
      residue (MR) of a drug in a target tissue of food animals. The MR is used to
      monitor potential unauthorized use of drugs. The current work is a continuation
      of our efforts to study metabolism and depletion profiles of albendazole in
      multiple finfish species to determine a common MR. The results of this study
      suggest that albendazole sulfone metabolite could potentially serve as MR for
      albendazole in yellow perch muscle, similar to channel catfish and hybrid striped
      bass as reported previously by us.

PMID- 22150531
TI  - Myocardial fibrosis is associated with biventricular dysfunction in patients with
      hypertrophic cardiomyopathy.
AB  - AIMS: To assess left (LV) and right ventricular (RV) function by two-dimensional
      (2D) speckle tracking echocardiography and its relation to myocardial fibrosis in
      hypertrophic cardiomyopathy (HCM). METHODS: We enrolled 50 HCM patients (30 male;
      47.3 +/- 9.9 years) in our study. Each patient received echocardiography with
      modern high-end scanners. For speckle tracking analysis of LV and RV function the
      dedicated software was used. The presence of myocardial fibrosis was detected by
      cardiac magnetic resonance imaging (MRI). RESULTS: For intraobserver variability
      of RV global longitudinal strain, we found a correlation of r = 0.89 (p < 0.001)
      with a minor bias of 4.9 +/- 2.9%. On cardiac MRI 30 patients (60%) demonstrated
      late gadolinium-enhancement (LGE) of the LV. Of these patients only 7% showed LGE
      of the RV. HCM patients with myocardial fibrosis had less global longitudinal LV
      strain in comparison to patients without myocardial fibrosis (-12.8 +/- 2.2 vs 
      21.1 +/- 2.6, P < 0.001), thicker interventricular septums (23.7 +/- 4.0 vs 19.2
      +/- 5.1, P < 0.001), larger left atria (34.9 +/- 7.1 vs 23.9 +/- 5.1, P < 0.001),
      and impaired diastolic function (E/A-ratio: 1.02 +/- 0.22 vs 1.15 +/- 0.18, P <
      0.01). Comparable results were found for RV function. LV and RV strain correlated
      with r = 0.85 (p < 0.001). CONCLUSIONS: HCM is not only a disease of the LV. LGE
      in HCM is associated with both LV and RV dysfunction. Although RV LGE occurs only
      in a minority of patients with HCM and LV fibrosis, speckle tracking
      echocardiography is feasible for evaluating LV and RV dysfunction in these
      patients.

PMID- 22150532
TI  - Maternal deletion allele of Angiotensin-converting enzyme gene is associated with
      fetal growth restriction.
AB  - To investigate the correlation between maternal and fetal angiotensin-converting
      enzyme gene insertion or deletion polymorphism and birth size, angiotensin
      converting enzyme gene insertion or deletion polymorphisms of 470 Japanese pairs
      of mothers and infants were genotyped. The relationships between maternal and
      fetal angiotensin-converting enzyme gene insertion or deletion polymorphisms and
      birth sizes (weight, length, head circumference, and the incidence of small-for
      gestational age status) were analyzed. No relationship between fetal angiotensin
      converting enzyme genotype and birth size was observed. In contrast, the
      incidence of small-for-gestational age status in babies whose mothers had 1 or 2
      deletion alleles was greater than that in babies whose mothers had 2 insertion
      alleles (7% vs 3%, P  =  0.045). Maternal deletion allele of angiotensin
      converting enzyme is associated with fetal growth restriction in the Japanese
      normal population.

PMID- 22150535
TI  - Are mesalazine granules superior to Eudragit-L-coated mesalazine tablets for
      induction of remission in distal ulcerative colitis?

PMID- 22150536
TI  - Sequential therapy--more studies are still required.

PMID- 22150538
TI  - Does the oral adsorbent AST-120 really improve symptoms for non-constipating
      irritable bowel syndrome?

PMID- 22150540
TI  - Carbon-based compounds emerging as sparkling diamonds for IBS treatment?

PMID- 22150542
TI  - Hypertransaminasemia and coeliac disease.

PMID- 22150544
TI  - The diagnosis of non-alcoholic fatty liver disease.

PMID- 22150546
TI  - The relationship of the canine femoral head to the femoral neck: an anatomic
      study with relevance for hip arthroplasty implant design and implantation.
AB  - OBJECTIVES: (1) To evaluate a novel method for characterizing the relationship of
      the canine femoral head to the femoral neck and (2) to determine whether the
      femoral head is symmetrically positioned upon the femoral neck. STUDY DESIGN:
      Cadaveric study. SAMPLE POPULATION: Cadaveric dog femurs (16 dogs, 32 femurs)
      METHODS: Femurs were photographed in frontal and sagittal planes simultaneously
      using 2 cameras positioned orthogonally. Ten measurements were made by 2
      independent observers and agreement assessed by calculating intraclass
      correlation coefficients (ICC). Repeatability in specimen positioning was
      assessed by repositioning and imaging a single femur10 times. RESULTS: ICC values
      exceeded 0.6 for 8 of the 10 different measurements made. Mean +/- SD femoral
      head offset ratios in the frontal and sagittal planes were 0.14 +/- 0.08 and 2.66
      +/- 1.16. The mean specimen positioning error (+/-SD) for the single specimen
      that was repositioned 10 times was 0.93 degrees  +/- 1.92 degrees  and 2.39
      degrees  +/- 1.13 degrees  in the frontal and sagittal planes, respectively.
      CONCLUSIONS: Correlations between observers were moderately strong or strong for
      8 of 10 measurements. Specimen positioning was repeatable. The offset ratios
      indicate that dogs have a substantial cranial and ventral offset of the femoral
      head from the femoral neck.

PMID- 22150549
TI  - Small nuclear size of Merkel cell tumors is a useful indicator of poor prognosis.

PMID- 22150547
TI  - The type of dietary fat modulates intestinal tight junction integrity, gut
      permeability, and hepatic toll-like receptor expression in a mouse model of
      alcoholic liver disease.
AB  - BACKGROUND: Interactions between the gut, immune system, and the liver, as well
      as the type of fat in the diet, are critical components of alcoholic liver
      disease (ALD). The goal of the present study was to determine the effects of
      saturated fat (SF) and unsaturated fat (USF) on ethanol (EtOH)-induced gut-liver
      interactions in a mouse model of ALD. METHODS: C57BL/6N mice were fed Lieber
      DeCarli liquid diets containing EtOH and enriched in USF (corn oil) or SF (medium
      chain triglycerides:beef tallow). Control mice were pair-fed on an isocaloric
      basis. Liver injury and steatosis, blood endotoxin levels, intestinal
      permeability, and tight junction (TJ) integrity, as well as hepatic Toll-like
      receptor (TLR) gene expression, were evaluated. RESULTS: After 8 weeks of EtOH
      feeding, liver injury and steatosis were observed in USF + EtOH group compared
      with control and SF + EtOH. Significantly increased intestinal permeability in
      conjunction with elevated blood endotoxin levels were observed in the ileal
      segments of the mice fed USF + EtOH. USF diet alone resulted in down-regulation
      of intestinal TJ protein mRNA expression compared with SF. Importantly, alcohol
      further suppressed TJ proteins in USF + EtOH, but did not affect intestinal TJ in
      SF + EtOH group. The type of fat in the diet alone did not affect hepatic TLR
      expression. Compared with control animals, hepatic TLR (TLR 1, 2, 3, 4, 7, 8, 9)
      mRNA expression was significantly (p < 0.05) increased in USF + EtOH, but not in
      SF + EtOH group. Notably, TLR5 was the only up-regulated TLR in both SF + EtOH
      and USF + EtOH groups. CONCLUSIONS: Dietary fat is an important cofactor in
      alcohol-associated liver injury. We demonstrate that USF (corn oil/linoleic acid)
      by itself results in dysregulation of intestinal TJ integrity leading to
      increased gut permeability, and alcohol further exacerbates these alterations. We
      postulate that elevated blood endotoxin levels in response to USF and alcohol in
      conjunction with up-regulation of hepatic TLRs combine to cause hepatic injury in
      ALD.

PMID- 22150548
TI  - TRM: a powerful two-stage machine learning approach for identifying SNP-SNP
      interactions.
AB  - Studies have shown that interactions of single nucleotide polymorphisms (SNPs)
      may play an important role in understanding the causes of complex disease. We
      have proposed an integrated machine learning method that combines two machine
      learning methods-Random Forests (RF) and Multivariate Adaptive Regression Splines
      (MARS)-to identify a subset of important SNPs and detect interaction patterns
      more effectively and efficiently. In this two-stage RF-MARS (TRM) approach, RF is
      first applied to detect a predictive subset of SNPs, and then MARS is used to
      identify the interaction patterns. We evaluated the TRM performances in four
      models. RF variable selection was based on out-of-bag classification error rate
      (OOB) and variable important spectrum (IS). Our results support that RF(OOB)  had
      better performance than MARS and RF(IS)  in detecting important variables. This
      study demonstrates that TRM(OOB) , which is RF(OOB)  plus MARS, has combined the
      strengths of RF and MARS in identifying SNP-SNP interactions in a scenario of 100
      candidate SNPs. TRM(OOB)  had greater true positive rate and lower false positive
      rate compared with MARS, particularly for searching interactions with a strong
      association with the outcome. Therefore, the use of TRM(OOB)  is favored for
      exploring SNP-SNP interactions in a large-scale genetic variation study.

PMID- 22150550
TI  - Minimally invasive postmortem telebiopsy.
AB  - For the past 10 years, medical imaging techniques have been increasingly applied
      to forensic investigations. To obtain histological and toxicological information,
      tissue and liquid samples are required. In this article, we describe the
      development of a low-cost, secure, and reliable approach for a telematic add-on
      for remotely planning biopsies on the Virtobot robotic system. Data sets are
      encrypted and submitted over the Internet. A plugin for the OsiriX medical image
      viewer allows for remote planning of needle trajectories that are used for needle
      placement. The application of teleradiological methods to image-guided biopsy in
      the forensic setting has the potential to reduce costs and, in conjunction with a
      mobile computer tomographic scanner, allows for tissue sampling in a mass
      casualty situation involving nuclear, biological, or chemical agents, in a manner
      that minimizes the risk to involved staff.

PMID- 22150551
TI  - Validation of MMPI-2-RF validity scales in criterion group neuropsychological
      samples.
AB  - This study utilized multiple criterion group neuropsychological samples to
      evaluate the "over-reporting" and "under-reporting" MMPI-2-RF validity scales.
      The five criterion groups included in this study were (1) litigating traumatic
      brain injury patients who failed Slick et al. criteria for probable malingering,
      (2) litigating traumatic brain injury patients who passed Slick et al. criteria,
      (3) mixed neuropsychological outpatients who passed SVTs and were diagnosed with
      primary neurological conditions, (4) mixed neuropsychological outpatients who
      passed SVTs and were diagnosed with primary psychiatric conditions, and (5)
      epileptic seizure disorder inpatients who were diagnosed via video-EEG. Using the
      data from these groups, cumulative percentages for all possible T-scores and
      sensitivity and specificity rates for optimal cutoff scores were determined. When
      specificity rates were set at 90% across all non-malingering neurological
      condition groups, sensitivity rates ranged from 48% (FBS-r) to 10% (K-r).

PMID- 22150552
TI  - Adolescent smoking behavior and outcome expectancies.
AB  - Adolescent smoking behavior is assumed to be associated with smoking outcome
      expectancies. Results in this paper are based on data from the control group of
      two data collections among Norwegian secondary school students taken
      approximately 30 months apart (T1 and T2). The dimensionality of smoking outcome
      expectancies was the same at both time points, revealing three components
      ("Addicted", "Not harmful" and "Social"). After correction for attenuation, the
      Pearson's correlation between T1 and T2 was 0.41 for the total sumscore,
      indicating low to moderate relative stability. When examining smoking expectancy
      sumscore means by smoking habits at T1 and T2, never smokers were different from
      smokers on both occasions. Never smokers scored low on "Social" and "Not
      harmful", and high on "Addictive". All associations were statistically
      significant (p < 0.001). The "Social" dimension was the strongest predictor of
      smoking behavior at T1 and T2. One of the outcome expectancy sumscores
      ("Addictive") at T1 predicted smoking habits at T2 after controlling for smoking
      habits at T1 (p < 0.01). This predictor was significant also after entering
      outcome expectancy sumscores at T2 into the model (p < 0.05). These results
      indicate that outcome expectations other than the health-related ones should be
      paid attention to when planning new prevention programs.

PMID- 22150553
TI  - Emotional stress-induced seizures: another reflex epilepsy?
AB  - Multiple triggers have been shown to provoke seizures in reflex epilepsy. Among
      these are external stimuli (flickering light, hot water), actions (chewing,
      reading), and even mental tasks. We present a 9-year-old girl whose seizures were
      provoked mainly by emotional stress. In most cases of emotional stress-related
      seizures, especially when a specific confrontational incidence preceded the
      seizure, the suspicion for a nonepileptic event is high. In our patient we were
      able to show that the seizures were epileptic. Further investigation to clarify
      the pathophysiology of stress-related seizures is needed.

PMID- 22150554
TI  - Facilitating access to sexual health services for men who have sex with men and
      male-to-female transgender persons in Guatemala City.
AB  - The purpose of this study was to identify barriers to accessing sexual health
      services among gay, bisexual and heterosexual-identifying men who have sex with
      men and male-to-female transgender persons in Guatemala City, to inform the
      development of high quality and population-friendly services. In-depth, semi
      structured interviews were conducted with 29 purposively sampled individuals,
      including 8 transgender, 16 gay/bisexual and 5 heterosexual-identifying
      participants. Topical codes were applied to the data using software Atlas.tiTM to
      compare data between sub-groups. Analysis revealed that public clinics were most
      commonly used due to their lower cost and greater accessibility, but many
      participants experienced discrimination, violation of confidentiality and
      distrust of these services. Transgender and gay/bisexual-identifying participants
      preferred clinics where they felt a sense of belonging, while heterosexual
      identifying participants preferred clinics unassociated with the men who have sex
      with men community. The most prominent barriers to sexual health services
      included fear of discrimination, fear of having HIV, cost and lack of social
      support. Findings highlight the need to strengthen existing public sexually
      transmitted infection clinics so that they address the multiple layers of stigma
      and discrimination that men who have sex with men and transgender persons
      experience.

PMID- 22150555
TI  - Perceived behavioural control and coping planning predict dental brushing
      behaviour among Iranian adolescents.
AB  - BACKGROUND AND AIM: The aim of this prospective study was to test the role of the
      direct predictors in the theory of planned behaviour (TPB), perceived behavioural
      control (PBC) and intention as well as action planning and coping planning as
      predictors of changes in dental brushing behaviour among Iranian adolescents.
      MATERIALS AND METHODS: One thousand students were selected from 57 high schools
      in Qazvin, IR Iran. N = 983 participants completed an initial questionnaire at
      Time 1 and they were asked to complete a follow-up questionnaire 1 month later
      (Time 2). At Time 1, PBC, behavioural intention, action planning and coping
      planning were assessed. Dental brushing behaviour was assessed both at Time 1 and
      4 weeks later at Time 2. A hierarchical regression analysis was conducted to
      examine the predictive validity of PBC, intention, action planning and coping
      planning both, as main effects and as interactions on dental brushing behaviour.
      RESULTS: Past behaviour, gender and age explained 46.5% of the variance in dental
      brushing at Time 2 in step 1. Adding intention to brush, PBC, action planning and
      coping planning in the second and third step explained an additional 24.9% of the
      variance in dental brushing at Time 2. Adding the interactions terms for action
      planning * coping planning, action planning * PBC and coping planning * PBC
      further increased the predictive validity of the model by 6.00% over and above
      the main effects. CONCLUSION: Intentions, PBC, action planning and coping
      planning are predictive variables for oral self-care behaviour. This finding
      suggests that an intervention simultaneously targeting PBC, action planning and
      coping planning might be particularly promising to promote oral self-care in
      adolescence.

PMID- 22150556
TI  - A novel glutaredoxin domain-containing peroxiredoxin 'All1541' protects the N2
      fixing cyanobacterium Anabaena PCC 7120 from oxidative stress.
AB  - Prxs (peroxiredoxins) are ubiquitous thiol-based peroxidases that detoxify toxic
      peroxides. The Anabaena PCC 7120 genome harbours seven genes/ORFs (open reading
      frames) which have homology with Prxs. One of these (all1541) was identified to
      encode a novel Grx (glutaredoxin) domain-containing Prx by bioinformatic
      analysis. A recombinant N-terminal histidine-tagged All1541 protein was
      overexpressed in Escherichia coli and purified. Analysis with the protein
      alkylating agent AMS (4-acetamido-4'-maleimidyl-stilbene-2,2'-disulfonate) showed
      All1541 to form an intra-molecular disulfide bond. The All1541 protein used
      glutathione (GSH) more efficiently than Trx (thioredoxin) to detoxify H(2)O(2).
      Deletion of the Grx domain from All1541 resulted in loss of GSH-dependent
      peroxidase activity. Employing site-directed mutagenesis, the cysteine residues
      at positions 50 and 75 were identified as peroxidatic and resolving cysteine
      residues respectively, whereas both the cysteine residues within the Grx domain
      (positions 181 and 184) were shown to be essential for GSH-dependent peroxidase
      activity. On the basis of these data, a reaction mechanism has been proposed for
      All1541. In vitro All1541 protein protected plasmid DNA from oxidative damage. In
      Anabaena PCC 7120, all1541 was transcriptionally activated under oxidative
      stress. Recombinant Anabaena PCC 7120 strain overexpressing All1541 protein
      showed superior oxidative stress tolerance to H(2)O(2) as compared with the wild
      type strain. The results suggest that the glutathione-dependent peroxidase
      All1541 plays an important role in protecting Anabaena from oxidative stress.

PMID- 22150557
TI  - Identification of cytokines and signaling proteins differentially regulated by
      sumatriptan/naproxen.
AB  - OBJECTIVES: The goal of this study was to use protein array analysis to
      investigate temporal regulation of stimulated cytokine expression in trigeminal
      ganglia and the spinal trigeminal nucleus in response to co-treatment of
      sumatriptan and naproxen sodium or individual drug. BACKGROUND: Activation of
      neurons and glia in trigeminal ganglia and the spinal trigeminal nucleus leads to
      increased levels of cytokines that promote peripheral and central sensitization,
      which are key events in migraine pathology. While recent clinical studies have
      provided evidence that a combination of sumatriptan and naproxen sodium is more
      efficacious in treating migraine than either drug alone, it is not well
      understood why the combination therapy is superior to monotherapy. METHODS: Male
      Sprague-Dawley rats were left untreated (control), injected with capsaicin, or
      pretreated with sumatriptan/naproxen, sumatriptan, or naproxen for 1 hour prior
      to capsaicin. Trigeminal ganglia and the spinal trigeminal nucleus were isolated
      2 and 24 hours after capsaicin or drug treatment, and levels of 90 proteins were
      determined using a RayBio(r) Label-Based Rat Antibody Array (RayBiotech,
      Norcross, GA, USA). RESULTS: Capsaicin stimulated a >3-fold increase in
      expression of the majority of cytokines in trigeminal ganglia at 2 hours that was
      sustained at 24 hours. Significantly, treatment with sumatriptan/naproxen almost
      completely abolished the stimulatory effects of capsaicin at 2 and 24 hours.
      Capsaicin stimulated >3-fold expression of more proteins in the spinal trigeminal
      nucleus at 24 hours when compared to 2 hours. Similarly, sumatriptan/naproxen
      abolished capsaicin stimulation of proteins in the spinal trigeminal nucleus at 2
      hours and greatly suppressed protein expression 24 hours post-capsaicin
      injection. Interestingly, treatment with sumatriptan alone suppressed expression
      of different cytokines in trigeminal ganglia and the spinal trigeminal nucleus
      than repressed by naproxen sodium. CONCLUSION: We found that the combination of
      sumatriptan/naproxen was effective in blocking capsaicin stimulation of pro
      inflammatory proteins implicated in the development of peripheral and central
      sensitization in response to capsaicin activation of trigeminal neurons. Based on
      our findings that sumatriptan and naproxen regulate expression of different
      proteins in trigeminal ganglia and the spinal trigeminal nucleus, we propose that
      these drugs function on therapeutically distinct cellular targets to suppress
      inflammation and pain associated with migraine.

PMID- 22150558
TI  - Comparative assessment of analytical approaches to quantify the risk for
      introduction of rare animal diseases: the example of avian influenza in Spain.
AB  - Trade of animals and animal products imposes an uncertain and variable risk for
      exotic animal diseases introduction into importing countries. Risk analysis
      provides importing countries with an objective, transparent, and internationally
      accepted method for assessing that risk. Over the last decades, European Union
      countries have conducted probabilistic risk assessments quite frequently to
      quantify the risk for rare animal diseases introduction into their territories.
      Most probabilistic animal health risk assessments have been typically classified
      into one-level and multilevel binomial models. One-level models are more simple
      than multilevel models because they assume that animals or products originate
      from one single population. However, it is unknown whether such simplification
      may result in substantially different results compared to those obtained through
      the use of multilevel models. Here, data used on a probabilistic multilevel
      binomial model formulated to assess the risk for highly pathogenic avian
      influenza introduction into Spain were reanalyzed using a one-level binomial
      model and their outcomes were compared. An alternative ordinal model is also
      proposed here, which makes use of simpler assumptions and less information
      compared to those required by traditional one-level and multilevel approaches.
      Results suggest that, at least under certain circumstances, results of the one
      level and ordinal approaches are similar to those obtained using multilevel
      models. Consequently, we argue that, when data are insufficient to run
      traditional probabilistic models, the ordinal approach presented here may be a
      suitable alternative to rank exporting countries in terms of the risk that they
      impose for the spread of rare animal diseases into disease-free countries.

PMID- 22150559
TI  - Pathogenesis of marked pituitary enlargement and increased serum thyroid
      stimulating hormone in primary hypothyroidism.

PMID- 22150560
TI  - Oncogenic alterations in papillary thyroid cancers of young patients.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) in young people usually has an
      aggressive initial presentation, though a good general prognosis despite
      recurrences in 10%-20% of patients. A number of genetic alterations that activate
      the mitogen-activated protein kinase (MAPK) pathway have been found in PTC. Some
      of these alterations have been identified as prognostic factors of PTC in adults.
      The objective of the current study was to comprehensively characterize all known
      oncogenic alterations of the MAPK pathway in young people. METHODS: One hundred
      three PTCs removed from 9 children, 19 adolescents, and 75 young adults were
      submitted to molecular analyses. RESULTS: Altogether, 57 alterations were found
      in 56 PTCs (55%) corresponding to V600E BRAF in 20.3%, RAS mutations in 12.6%,
      RET/PTC 1 in 11.6%, RET/PTC 3 in 8.7%, and rearrangement of NTRK in 1.9%. The
      prevalence of all alterations increased with age (22.2% in children; 52.6% in
      adolescents, 51.4% in adults 20-25 years, and 55.1% in adults 25-35 years).
      Prevalence increased from 39.2% earlier to 61.3% after 20 years mainly due to
      BRAF mutations. Classic-type PTC was associated with a larger prevalence of
      alterations, predominantly BRAF and RET/PTC, whereas the follicular variant was
      chiefly associated with RAS. RET/PTC (1 and 3) was significantly associated with
      extrathyroid extension (ET) and lymph node metastasis (es) (LNM). This
      association was found in the adult group. There were no associations of BRAF or
      RAS mutations with ET or LNM. A 3-year median follow up was available for 90
      patients. RET/PTC 1 and 3 was associated with short-term disease dissemination
      (cervical lymph node recurrences and distant metastases) in young adults
      (p=0.001). Persistent illness was more prevalent in patients with (15%) than in
      patients without (7%) genetic alterations. CONCLUSION: PTCs in young patients
      display a low prevalence of the already identified oncogenic alterations. The
      increasing prevalence with age is mainly due to V600E BRAF mutation. There is no
      relation between tumor aggressiveness and BRAF mutation. There is a relation
      between the presence of RET/PTC (1 and 3) and the histological and clinical short
      term aggressiveness of PTC in the population of young adults. Such a relation is
      not found in children and adolescents.

PMID- 22150561
TI  - Systematic review of the efficacy and safety of fibrinogen concentrate
      substitution in adults.
AB  - BACKGROUND: A sufficient plasma level of fibrinogen is critical for the formation
      of a fibrin clot and haemostasis in both the perioperative setting and in massive
      haemorrhage. We assessed the efficacy and safety of fibrinogen concentrate
      substitution in the perioperative setting and in massive haemorrhage. METHODS: We
      conducted a systematic literature search for studies conducted on humans and
      published in either English or German in several databases from 1985 to 2010. In
      addition, we screened several web sites for assessments on fibrinogen concentrate
      substitution and conducted a hand search using Scopus. In terms of efficacy, we
      included all prospective, controlled studies. Concerning safety, we included all
      prospective studies. RESULTS: We identified two randomised controlled trials and
      two non-randomised controlled studies, which included a total of 74 patients. The
      studies indicate that the administration of fibrinogen concentrate is associated
      with improved clot firmness and reduction in the substitution of other blood
      products such as red blood cells, fresh frozen plasma and platelet concentrates,
      as well as decreased post-operative bleeding and drainage volume. In addition,
      fibrinogen concentrate administration has been reported to be safe with regard to
      thrombosis and thromboembolic complications, as well as mortality. However, the
      studies identified were of poor quality. CONCLUSION: In conclusion, the results
      of the available controlled trials suggest that the administration of fibrinogen
      concentrate was effective and safe. However, because all studies identified were
      of inadequate quality, these findings need to be confirmed by randomised
      controlled trials of sufficient size and long-term follow-up.

PMID- 22150563
TI  - The prediction and cost of futility in the NICU.
AB  - AIM: To quantify the cost and prediction of futile care in the Neonatal Intensive
      Care Unit (NICU). METHODS: We observed 1813 infants on 100,000 NICU bed days
      between 1999 and 2008 at the University of Chicago. We determined costs and
      assessed predictions of futility for each day the infant required mechanical
      ventilation. RESULTS: Only 6% of NICU expenses were spent on nonsurvivors, and in
      this sense, they were futile. If only money spent after predictions of death is
      considered, futile expenses fell to 4.5%. NICU care was preferentially directed
      to survivors for even the smallest infants, at the highest risk to die. Over 75%
      of ventilated NICU infants were correctly predicted to survive on every day of
      ventilation by every caretaker. However, predictions of 'die before discharge'
      were wrong more than one time in three. Attendings and neonatology fellows tended
      to be optimistic, while nurses and neonatal nurse practitioners tended to be
      pessimistic. CONCLUSIONS: Criticisms of the expense of NICU care find little
      support in these data. Rather, NICU care is remarkably well targeted to patients
      who will survive, particularly when contrasted with care in adult ICUs. We
      continue to search for better prognostic tools for individual infants.

PMID- 22150562
TI  - Wnt/beta-catenin pathway regulates bone morphogenetic protein (BMP2)-mediated
      differentiation of dental follicle cells.
AB  - BACKGROUND AND OBJECTIVE: Bone morphogenetic protein 2 (BMP2)-induced osteogenic
      differentiation has been shown to occur through the canonical Wnt/betacatenin
      pathway, whereas factors promoting canonical Wnt signaling in cementoblasts
      inhibit cell differentiation and promote cell proliferation in vitro. The aim of
      this study was to investigate whether putative precursor cells of cementoblasts,
      dental follicle cells (murine SVF4 cells), when stimulated with BMP2, would
      exhibit changes in genes/proteins associated with the Wnt/beta-catenin pathway.
      MATERIAL AND METHODS: SVF4 cells were stimulated with BMP2, and the following
      assays were carried out: (i) Wnt/beta-catenin pathway activation assessed by
      western blotting, beta-catenin/transcription factor (TCF) reporter assays and
      expression of the lymphoid enhancer-binding factor-1 (Lef1), transcription factor
      7 (Tcf7), Wnt inhibitor factor 1 (Wif1) and Axin2 (Axin2) genes; and (ii)
      cementoblast/osteoblast differentiation assessed by mineralization in vitro, and
      by the mRNA levels of runt-related transcription factor 2 (Runx2), osterix (Osx),
      alkaline phosphatase (Alp), osteocalcin (Ocn) and bone sialoprotein (Bsp),
      determined by quantitative PCR after treatment with wingless-type MMTV
      integration site family, member 3A (WNT3A) and knockdown of beta-catenin.
      RESULTS: WNT3A induced beta-catenin nuclear translocation and up-regulated the
      transcriptional activity of a canonical Wnt-responsive reporter, suggesting that
      the Wnt/beta-catenin pathway functions in SVF4 cells. Activation of Wnt signaling
      with WNT3A suppressed BMP2-mediated induction of cementoblast/osteoblast
      maturation of SVF4 cells. However, beta-catenin knockdown showed that the BMP2
      induced expression of cementoblast/osteoblast differentiation markers requires
      endogenous beta-catenin. WNT3A down-regulated transcripts for Runx2, Alp and Ocn
      in SVF4 cells compared with untreated cells. In contrast, BMP2 induction of Bsp
      transcripts occurred independently of Wnt/beta-catenin signaling. CONCLUSION:
      These data suggest that stabilization of beta-catenin by WNT3A inhibits BMP2
      mediated induction of cementoblast/osteoblast differentiation in SVF4 cells,
      although BMP2 requires endogenous Wnt/beta-catenin signaling to promote cell
      maturation.

PMID- 22150564
TI  - Effect of endocrine treatment on voiding and prostate size in men with prostate
      cancer: a long-term prospective study.
AB  - OBJECTIVE: The aim of this study was to assess and quantify changes in voiding
      parameters and prostate size in men with prostate cancer from before the start of
      endocrine treatment and during long-term follow-up. MATERIAL AND METHODS: Seventy
      seven patients were recruited from three clinics and followed prospectively until
      death, clinical deterioration making the patient unfit for participation, or the
      end of the study. Median age was 74 (range 54-85) years, and the median follow-up
      was 18 (3-90) months. Parameters and endpoints were total score on the Danish
      Prostatic Symptom Score (DAN-PSS-1) questionnaire, maximum flow rate, postvoid
      residual volume, frequency and voided volume, and prostate volume on transrectal
      ultrasonography. RESULTS: All parameters improved significantly in the range of
      median 13-50% within the first 12 months. The greater part of the effect occurred
      during the first month, and thereafter the improvement rate slowed down.
      Intervention for local progression was estimated on Kaplan-Meier analysis to be
      about 20% after 4 years. 73% had a defined prostate-specific antigen nadir after
      a median of 6 (1-60) months with scheduled assessments up to 72 months after the
      nadir. All parameters were improved before the nadir and the improvement remained
      during biochemical progression except for the very latest visits where few
      patients contributed to the analyses. CONCLUSIONS: Androgen deprivation therapy
      improved lower urinary tract symptoms, objective voiding parameters and prostate
      volume in patients with prostate cancer who were not candidates for curative
      treatment. The improvement was significant within the first month and clinically
      relevant. Despite biochemical progression the effect may last for years, and only
      a minority will need intervention for local progression.

PMID- 22150565
TI  - Response-level probability effects on reaction time: now you see them, now you
      don't.
AB  - Many reaction time (RT) experiments have tested for response-level probability
      effects. Their results have been mixed, which is surprising because
      psychophysiological studies provide clear evidence of motor-level changes
      associated with an anticipated response. A survey of the designs used in the RT
      studies reveals many potential problems that could conceal the effects of
      response probability. We report five new RT experiments testing for response
      level probability effects with the most promising of the previous designs-that of
      Blackman ( 1972 )-and with new designs. Some of these experiments yield evidence
      of response-level probability effects, but others do not. It appears that
      response-level probability effects are present primarily in simple tasks with a
      strong emphasis on response preparation, possibly because participants only
      expend effort on response preparation in these tasks.

PMID- 22150566
TI  - Use of locking plate and screws for triple pelvic osteotomy.
AB  - OBJECTIVE: To evaluate the efficacy and complication rate associated with use of
      a purpose-specific locking triple pelvic osteotomy (LTPO) plate. STUDY DESIGN:
      Prospective study. ANIMALS: Dogs (n = 9; 15 hips). METHODS: Physical examination,
      plain film radiography, computed tomography (CT) of the pelvis, and coxofemoral
      arthroscopy were performed before unilateral triple pelvic osteotomy (TPO) or
      staged bilateral TPO. Radiographs were taken after each procedure and 3-5, 6-8,
      and >=12 weeks postoperatively. Pelvic width was measured at 3 locations to
      evaluate pelvic canal narrowing. RESULTS: No screw loosening occurred.
      Complications occurred in only 1 hip (7%) where pullout of the locking plate
      screw construct from the caudal iliac segment occurred because of a fracture of
      the cis-cortex; the dog made a full recovery after a salvage procedure. There was
      no significant reduction in the cranial pelvic width but a small reduction at the
      level of the acetabuli and ischiatic tuberosities was noted 3-5 weeks after the
      2nd TPO. CONCLUSIONS: The LTPO plate was associated with a lower complication
      rate than previously reported for TPOs using Slocum canine pelvic osteotomy
      plates (CPOP) and warrants further investigation. Pullout of the caudal plate
      screw construct is a complication specific to LTPO implants. Bicortical screw
      purchase is recommended to prevent fracture of the cis-cortex and implant
      pullout.

PMID- 22150567
TI  - Diastolic cardiac function is synonymous with long-axis systolic function: a
      novel concept in cardiac function.
AB  - AIMS: There has been recent speculation on the relationship between diastolic
      cardiac function and long-axis cardiac function. The goal of this study was to
      obtain conclusive evidence regarding the relationship between these parameters.
      METHODS: Echocardiography and cardiac magnetic resonance imaging were performed
      consecutively in 33 subjects. Longitudinal fractional shortening and fractional
      shortening of the left ventricular wall length were measured in each procedure
      and the relationships with diastolic cardiac function were assessed. RESULTS:
      Diastolic cardiac function and long-axis systolic function in each procedure were
      significantly correlated. Spearman coefficients for correlations between
      longitudinal fractional shortening measured echocardiographically and diastolic
      cardiac function parameters were 0.76 (P < 0.0001) for E/A, -0.77 (P < 0.0001)
      for E/e', 0.87 (P < 0.0001) for e', and 0.91 (P < 0.0001) for e'/a'. CONCLUSIONS:
      Long-axis cardiac function correlates well with diastolic cardiac function. e'/a'
      showed a strong correlation with longitudinal fractional shortening and is a good
      candidate for use as an index for assessment of long-axis cardiac function.

PMID- 22150568
TI  - Pharmacokinetics of florfenicol and florfenicol-amine after intravenous
      administration in sheep.

PMID- 22150569
TI  - Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730
      rectal enema in children with active distal ulcerative colitis.
AB  - BACKGROUND: Intestinal microbiota manipulation, one of the pathogenetic
      components of inflammatory bowel disease (IBD), has become an attractive therapy
      for ulcerative colitis (UC). AIM: To assess in children with active distal UC the
      effectiveness of Lactobacillus (L) reuteri ATCC 55730 enema on inflammation and
      cytokine expression of rectal mucosa. METHODS: A total of 40 patients (median
      age: 7.2 years range 6-18) with mild to moderate UC were enrolled in a
      prospective, randomised, placebo-controlled study. They received an enema
      solution containing 10(10) CFU of L. reuteri ATCC 55730 or placebo for 8 weeks,
      in addition to oral mesalazine. Clinical endoscopic and histological scores as
      well as rectal mucosal expression levels of IL-10, IL-1beta, TNFalpha and IL-8
      were evaluated at the beginning and at the end of the trial. RESULTS: Thirty-one
      patients accomplished the trial (17 males, median age 13 year, range 7-18). Mayo
      score (including clinical and endoscopic features) decreased significantly in the
      L. reuteri group (3.2 +/- 1.3 vs. 8.6 +/- 0.8, P < 0.01) compared with placebo
      (7.1 +/- 1.1 vs. 8.7 +/- 0.7, NS); furthermore, histological score significantly
      decrease only in the L. reuteri group (0.6 +/- 0.5 vs. 4.5 +/- 0.6, P < 0.01)
      (placebo: 2.9 +/- 0.8 vs. 4.6 +/- 0.6, NS). At the post-trial evaluation of
      cytokine mucosal expression levels, IL-10 significantly increased (P < 0.01)
      whereas IL-1beta, TNFalpha and IL-8 significantly decreased (P < 0.01) only in
      the L. reuteri group. CONCLUSIONS: In children with active distal ulcerative
      colitis, rectal infusion of L. reuteri is effective in improving mucosal
      inflammation and changing mucosal expression levels of some cytokines involved in
      the mechanisms of inflammatory bowel disease.

PMID- 22150570
TI  - Chronic alcohol exposure alters gene expression in HepG2 cells.
AB  - BACKGROUND: The liver is the primary site of alcohol metabolism and is highly
      vulnerable to injuries due to chronic alcohol abuse. Several molecular
      mechanisms, including oxidative stress and altered cellular metabolism, have been
      implicated in the development and progression of alcoholic liver disease. We
      sought to gain further insight into the molecular pathogenesis by studying the
      effects of ethanol exposure on the global gene expression in HepG2 cells.
      METHODS: HepG2 cells were cultured in the presence or absence of 75 mM ethanol
      for 9 days, with fresh media daily. Global gene expression changes were studied
      using Affymetrix GeneChip((r)) Human Exon 1.0 ST Arrays. Gene expression
      differences were validated for 13 genes by quantitative real-time RT-PCR. To
      identify biological pathways affected by ethanol treatment, differentially
      expressed genes were analyzed by Ingenuity Pathway Analysis software. RESULTS:
      Long-term ethanol exposure altered the expression of 1,093 genes (false discovery
      rate <= 3%); many of these changes were modest. Long-term ethanol exposure
      affected several pathways, including acute phase response, amino acid metabolism,
      carbohydrate metabolism, and lipid metabolism. CONCLUSIONS: Global measurements
      of gene expression show that a large number of genes are affected by chronic
      ethanol, although most show modest effect. These data provide insight into the
      molecular pathology resulting from extended alcohol exposure.

PMID- 22150571
TI  - Toxicological findings in 889 fatally injured obese pilots involved in aviation
      accidents.
AB  - Prevalence of drugs in fatally injured obese pilots involved in aviation
      accidents has not been evaluated. Therefore, toxicological findings in such
      pilots (body mass index >=30 kg/m(2) ) were examined in a data set derived from
      the Civil Aerospace Medical Institute's (CAMI's) Scientific Information System
      for 1990-2005. Aeromedical histories of these aviators were retrieved from the
      CAMI medical certification and toxicology databases, and the cause/factors in the
      related accidents from the National Transportation Safety Board's database. In
      311 of the 889 pilots, carbon monoxide, cyanide, ethanol, and drugs were found,
      and glucose and hemoglobin A(1c) were elevated. Of the 889 pilots, 107 had an
      obesity-related medical history. The health and/or medical condition(s) of,
      and/or the use of ethanol and/or drugs by, pilots were the cause/factors in 55
      (18%) of the 311 accidents. Drugs found were primarily for treating obesity
      related medical conditions such as depression, hypertension, and coronary heart
      disease.

PMID- 22150572
TI  - The relationship between HbA1c and fasting plasma glucose in patients with
      increased plasma liver enzyme measurements.
AB  - BACKGROUND: HbA(1c) is currently being introduced for diagnostic purpose in
      diabetes. Previous studies have, however, indicated that patients with liver
      disease have false low HbA(1c) levels. We therefore investigated the correlation
      between HbA(1c) and plasma glucose in patients with different levels of increased
      liver enzyme concentrations. METHODS: Data from 10,065 patients with simultaneous
      measurement of HbA(1c), venous fasting plasma glucose, alanine aminotransferase
      and gamma-glutamyl transferase were extracted from our laboratory database.
      Correlations were investigated in four patient groups divided according to their
      liver enzyme concentrations. RESULTS: The correlation between HbA(1c) and plasma
      glucose was high in all groups, with r = 0.77 for men and r = 0.78 for women (P <
      0.001), a correlation confirmed with multiple regression analysis (P < 0.001).
      However, interaction analysis revealed that linear regression lines were
      significantly different for men and women, with increase of both liver enzyme
      measurements and also, for women, with increased alanine aminotransferase. When
      compared with biological variation for HbA(1c), only men with increased
      measurements of both liver enzymes had a clinically important decrease in
      HbA(1c). CONCLUSIONS: Increased liver enzyme concentrations do not bias the
      correlation between HbA(1c) and fasting plasma glucose. However, men with low
      plasma glucose and increased concentrations of both liver enzymes do have a
      slightly decreased HbA(1c) and, if the clinical suspicion is strong enough, one
      should consider supplement testing.

PMID- 22150573
TI  - Pigmented plaque-type condyloma acuminatum associated with human papillomavirus
      type 6.

PMID- 22150575
TI  - How does it feel? Workplace bullying, emotions and musculoskeletal complaints.
AB  - The present study examines experienced emotions among self-labelled victims of
      ongoing workplace bullying and tests whether emotions mediate the relationship
      between exposure to bullying and health in the form of musculoskeletal
      complaints. A total of 1,024 employees from a Norwegian public transport company
      participated in the study, in which 116 self-labelled victims were identified.
      Ten positive and 10 negative emotions were measured (PANAS). The results showed
      significant differences in emotional experiences between victims and non-victims
      regarding all 10 negative emotions and one out of 10 positive emotions. Victims
      felt less "interested" and more "afraid," "upset," "angry," "guilty," "nervous,"
      "hostile," "frustrated," "ashamed," "scared" and "stressed" than did non-victims.
      Further, the results pointed to both positive and negative emotions as mediators
      of the relationship between exposure to bullying and musculoskeletal complaints.
      In particular the negative emotion "stress" acted as a significant mediator
      regarding this relationship. Hence, emotions seem to be central to understanding
      the detrimental effects of bullying on the victims' health.

PMID- 22150574
TI  - Caregivers' oral health literacy and their young children's oral health-related
      quality-of-life.
AB  - OBJECTIVES: To investigate the association of caregivers' oral health literacy
      (OHL) with their children's oral health related-quality of life (C-OHRQoL) and
      explore literacy as a modifier in the association between children's oral health
      status (COHS) and C-OHRQoL. METHODS: This study relied upon data from structured
      interviews with 203 caregivers of children aged 3-5 from the Carolina Oral Health
      Literacy (COHL) Project. Data were collected for OHL using REALD-30, caregiver
      reported COHS using the NHANES-item and C-OHRQoL using the Early Childhood Oral
      Health Impact Scale (ECOHIS). This study also measured oral health behaviors
      (OHBs) and socio-demographic characteristics and calculated overall/stratified
      summary estimates for OHL and C-OHRQoL. Spearman's rho and 95% confidence
      intervals (CI) were computed as measures of correlation of OHL and COHS with C
      OHRQoL. To determine whether OHL modified the association between COHS and C
      OHRQoL, this study compared literacy-specific summary and regression estimates.
      RESULTS: Reported COHS was: excellent-50%, very good-28%, good-14%, fair-6%, poor
      2%. The aggregate C-OHRQoL mean score was 2.0 (95% CI: 1.4, 2.6), and the mean
      OHL score 15.9 (95% CI: 15.2, 16.7). There was an inverse relationship between
      COHS and C-OHRQoL: rho = -0.32 (95% CI: -0.45, -0.18). There was no important
      association between OHL and C-OHRQoL; however, deleterious OHBs were associated
      with worse C-OHRQoL. Literacy-specific linear and Poisson regression estimates of
      the association between COHS and C-OHRQoL departed from homogeneity (Wald chi(2)
      p < 0.2). CONCLUSION: In this community-based sample of caregiver/child dyads, a
      strong correlation was found between OHS and C-OHRQoL. The association's
      magnitude and gradient were less pronounced among caregivers with low literacy.

PMID- 22150576
TI  - Evaluating prognostic accuracy of biomarkers under competing risk.
AB  - To develop more targeted intervention strategies, an important research goal is
      to identify markers predictive of clinical events. A crucial step toward this
      goal is to characterize the clinical performance of a marker for predicting
      different types of events. In this article, we present statistical methods for
      evaluating the performance of a prognostic marker in predicting multiple
      competing events. To capture the potential time-varying predictive performance of
      the marker and incorporate competing risks, we define time- and cause-specific
      accuracy summaries by stratifying cases based on causes of failure. Such
      definition would allow one to evaluate the predictive accuracy of a marker for
      each type of event and compare its predictiveness across event types. Extending
      the nonparametric crude cause-specific receiver operating characteristics curve
      estimators by Saha and Heagerty (2010), we develop inference procedures for a
      range of cause-specific accuracy summaries. To estimate the accuracy measures and
      assess how covariates may affect the accuracy of a marker under the competing
      risk setting, we consider two forms of semiparametric models through the cause
      specific hazard framework. These approaches enable a flexible modeling of the
      relationships between the marker and failure times for each cause, while
      efficiently accommodating additional covariates. We investigate the asymptotic
      property of the proposed accuracy estimators and demonstrate the finite sample
      performance of these estimators through simulation studies. The proposed
      procedures are illustrated with data from a prostate cancer prognostic study.

PMID- 22150577
TI  - D2-40 is expressed on the luminal surface of pulmonary airspaces in normal
      developing and adult lung but is lost in conditions associated with intra
      alveolar infiltrates.
AB  - The D2-40 antigen is a glycosylated sialomucin that is strongly expressed by
      lymphatic endothelial cells. Recently we observed the expression of D2-40 on the
      luminal surface of pulmonary airspaces in lung sections. The aim of the study was
      to assess the expression of D2-40 antigen in normal lung development and in
      various pathologic conditions in which abnormal alveolar infiltrates were
      present. Formalin-fixed lung tissue was selected from 42 fetal/neonatal autopsy
      cases ranging in gestational age from 12 to 41 weeks and from 10 adult lungs. In
      the fetal/neonatal group, 22 cases were histologically normal, whereas 20 were
      abnormal (including cases of pneumonia, alveolar hemorrhage, meconium aspiration,
      pulmonary hypoplasia, and pulmonary interstitial emphysema). In the adult group,
      5 cases were histologically normal and 5 had pneumonia. Immunohistochemical
      staining was performed on all cases using antibody to D2-40. All cases of normal
      fetal/neonatal lung and normal adult lung showed diffuse strong expression of D2
      40 on the luminal surface of the alveolar lining cells. D2-40 expression was also
      noted on the bronchiolar lining cells of normal fetal/neonatal lung. In all cases
      in which there was an abnormal infiltrate or foreign material within the
      airspaces, expression of D2-40 was lost in the alveolar lining. The production of
      the D2-40 antigen in the alveolar lining occurs as early as 12 weeks gestation
      and continues to be present throughout all other stages of lung development, as
      well as in adult lung. These results suggest that D2-40 may have a cell membrane
      protective function.

PMID- 22150578
TI  - Sentencing risk: history of incarceration and HIV/STD transmission risk
      behaviours among Black men who have sex with men in Massachusetts.
AB  - This study investigated the role of incarceration in HIV/STD risk among 197 Black
      men who have sex with men in Massachusetts, USA. More than half (51%) reported a
      history of incarceration (28% < 90 days in jail/prison; 23% >= 90 days in
      jail/prison). Multivariable logistic regression models adjusted for age and
      sexual orientation examined associations between demographic, behavioural, social
      psychological and cultural factors and incarceration history. Factors associated
      with < 90 days of incarceration were: unprotected sex with a man, STD history,
      injection drug use and substance abuse treatment. Factors associated with >= 90
      days of incarceration were: unprotected sex with a woman, crack use during sex,
      STD history, injection drug use, substance abuse treatment, depressive symptoms,
      post-traumatic stress symptoms, HIV fatalism and social capital. Black men who
      have sex with men with incarceration histories may be at increased risk for
      HIV/STDs compared to those without such histories. HIV prevention efforts that
      focus on individual risk and cultural-contextual issues among Black men who have
      sex with men are warranted.

PMID- 22150579
TI  - Familial multiple pilomatrixomas as a presentation of attenuated adenomatosis
      polyposis coli.
AB  - Pilomatrixomas are benign follicular tumors that occur most commonly in children.
      Rare multiple or familial pilomatrixomas have been associated with myotonic
      dystrophy and other disorders. Although sporadic pilomatrixomas and hybrid
      cutaneous cysts with pilomatrixoma-like features have been observed in some
      kindreds with Gardner syndrome, an autosomal dominant form of familial
      adenomatous polyposis, no definitive association has been made with multiple or
      familial pilomatrixomas. Here we describe two siblings with multiple
      pilomatrixomas who were also found to have a family history of colonic
      adenocarcinoma. Genetic testing revealed a mutation in the 5' portion of the
      adenomatous polyposis coli (APC) gene, in a region associated with an attenuated
      APC phenotype. These findings show that multiple pilomatrixomas may be the
      presenting symptom of patients with APC gene mutations.

PMID- 22150580
TI  - Colonoscopist and primary care physician supply and disparities in colorectal
      cancer screening.
AB  - OBJECTIVE. : To determine whether racial/ethnic disparities in colonoscopy use
      vary by physician availability. DATA SOURCE. : We used 100 percent Texas Medicare
      claims data for 2003-2007. STUDY DESIGN. : We identified beneficiaries aged 66-79
      in 2007, examined racial/ethnic differences in colonoscopy use from 2003 to 2007,
      and estimated the percentage of white, black, and Hispanic beneficiaries who
      underwent colonoscopy by level of physician availability and area income.
      PRINCIPAL FINDINGS. : For the 974,879 beneficiaries, colonoscopy use was higher
      in whites (40.7 percent) compared to blacks (35.0 percent) and Hispanics (28.7
      percent, p< .001). For whites, increasing availability of colonoscopists and
      primary care physicians (PCPs) was associated with higher colonoscopy use. For
      blacks and Hispanics, colonoscopy use was unchanged or decreased with increases
      in colonoscopist and PCP availability. In multilevel models, the odds of
      colonoscopy were 20 percent lower for blacks (OR 0.80, 95 percent CI 0.79-0.82)
      and 32 percent lower for Hispanics (OR 0.68, 95 percent CI 0.66-0.69) compared to
      whites; adjusting for availability of colonoscopists or PCPs did not attenuate
      racial/ethnic disparities. We found greater racial/ethnic disparities in areas
      with greater colonoscopist and PCP availability. CONCLUSIONS. : Greater area
      availability of colonoscopists and PCPs is associated with increased use of
      colonoscopy in whites but decreased use in minorities, resulting in larger
      racial/ethnic disparities.

PMID- 22150581
TI  - Reliability and validity of the Swedish version of the modified Yale Preoperative
      Anxiety Scale.
AB  - BACKGROUND: The modified Yale Preoperative Anxiety Scale (m-YPAS) is an
      observational behavioral checklist that has been widely used as an indicator of
      pre-operative anxiety in children. The present study describes the translation
      process of m-YPAS into Swedish and the testing of its reliability and validity
      when used with Swedish children. METHODS: The questionnaire was translated using
      standard forward-back-forward translation technique. The validation process was
      divided into two phases: a pilot study with 61 children as a first version and a
      test of a final version with 102 children. RESULTS: The reliability tested with
      Cronbach's alpha was acceptable to good. Interrater reliability analyzed with
      weighted kappa was acceptable to good with Students Registered Nurse Anesthetists
      and Certified Registered Nurse Anesthetist (CRNA) as evaluators (phase 1) and
      good to excellent with CRNA's very experienced in child anesthesia (phase 2).
      Both concurrent and constructed validity could be demonstrated. CONCLUSION: This
      validation study of the Swedish version of the m-YPAS shows good consistency,
      interrater validity, and construct validity when used by experienced assessors.

PMID- 22150582
TI  - Is religiosity related to periodontal health among the adult Jewish population in
      Jerusalem?
AB  - BACKGROUND AND OBJECTIVE: Religiosity may be a relevant protective factor for
      periodontitis, as it is for other chronic systemic diseases. The objective of the
      present study was to assess the relationship between periodontitis and
      religiosity, and whether oral health-related behaviours, spirituality and social
      support are included in the potential pathways that explain the association
      between religiosity and periodontitis. MATERIAL AND METHODS: Cross-sectional data
      were part of a retrospective study. The stratified random-sampling technique was
      limited to the Jerusalem Jewish population. Conceptual hierarchical data analysis
      modelling was adopted, assuming that socio-economic position was the most distal
      determinant, age and gender were confounders, and social support, spirituality
      and oral health behaviours were mediators in the relationship between religiosity
      and periodontitis. RESULTS: Kappa intra-examiner values (0.89) were satisfactory.
      Response rate was 88.0%. The final sample included 123 men and 125 women. The
      mean age was 38.6 years (SD 3.25 years), with 33.9% declared to be 'orthodox',
      33.1% 'religious' and 33.1% 'secular'. Higher levels of religiosity (p=0.01),
      support of internal life through spirituality (p=0.03), higher family social
      support (p=0.02) and low levels of plaque (p=0.05) were related to lower levels
      of periodontitis. Religiosity led to higher family social support and support of
      internal life through spirituality, which was related to plaque level and
      periodontitis. CONCLUSION: Religiosity had a protective effect against
      periodontitis through extrinsic and intrinsic pathways. This should be considered
      as part of aetiology and prognosis, in potential prevention and care of
      periodontitis.

PMID- 22150583
TI  - The electroencephalogram of idiopathic generalized epilepsy.
AB  - Idiopathic generalized epilepsy (IGE) is classified into several subsyndromes
      based on clinical and electroencephalography (EEG) features. The EEG signature of
      IGE is bisynchronous, symmetric, and generalized spike-wave complex; although
      focal, irregular, and so called "fragments" of discharges are not uncommon. Other
      characteristic EEG features include polyspikes, polyspike-wave discharges,
      occipital intermittent rhythmic delta activity, and photoparoxysmal response.
      Both human and animal data suggest involvement of the thalamus and the cortex in
      the generation of spike-wave discharges in IGE. Circadian variations of
      generalized epileptiform discharges are well described, and these can be useful
      in diagnostic confirmation. Those discharges tend to occur more often after
      awakening and during cyclic alternating pattern phase-A of non-rapid eye movement
      sleep. Activation procedures such as hyperventilation, intermittent photic
      stimulation, eye closure, and fixation-off are useful techniques to increase the
      yield of both interictal and ictal EEG abnormalities. Although not in routine
      use, specific triggers such as pattern stimulation and cognitive tasks may also
      be of value in eliciting rare reflex seizure-related EEG abnormalities.
      Variations of EEG abnormalities are evident between different electroclinical
      syndromes. EEG is also affected by certain external as well as internal factors,
      which should be borne in mind when interpreting EEG studies in IGE.

PMID- 22150584
TI  - Changes in care and short-term outcome for very preterm infants in Estonia.
AB  - AIM: To identify recent changes in short-term outcome and care for very preterm
      infants in Estonia. METHODS: Comparison of two population-based cohort of very
      preterm infants born alive at 22-31 gestational weeks. In 2007-2008, data were
      recorded prospectively in a neonatal register. For the cohort born in 2002-2003,
      the same variables were extracted retrospectively from the hospital records.
      Infants were followed up to discharge or death. RESULTS: The cohort of 2007-2008
      contained a higher proportion of infants born by caesarean section and of infants
      who received antenatal corticosteroids, maternal antibiotics, or surfactant
      therapy than the earlier cohort. A higher proportion of infants was admitted for
      care in 2007-2008 (98% vs. 94%; p = 0.013). During the study period, survival
      until discharge increased (85% vs. 78%; p = 0.041), although the length of
      hospital stay was unchanged. The use of mechanical ventilation, inotropes, and
      postnatal antibiotics decreased. Neonatal morbidity remained unchanged, except
      for a decrease in severe periventricular/intraventricular haemorrhage.
      CONCLUSION: The outcome for very preterm infants in Estonia has improved since
      2002. With proactive perinatal management and less invasive neonatal care,
      survival until discharge increased without concomitant increases in neonatal
      morbidity and the length of hospital stay.

PMID- 22150585
TI  - Ocular epidemiology and genetics.

PMID- 22150586
TI  - Worldwide prevalence and risk factors for myopia.
AB  - BACKGROUND: Myopia, the most common type of refractive error, is a complex trait
      including both genetic and environmental factors. Numerous studies have tried to
      elucidate the aetiology of myopia. However, the exact aetiology of myopia is
      still unclear. PURPOSE: To summarize the worldwide patterns and trends for the
      prevalence of myopia and to evaluate the risk factors for myopia in population
      based studies. RECENT FINDINGS: The prevalences of myopia vary across populations
      of different regions and ethnicities. In population-based studies on children,
      the prevalence of myopia has been reported to be higher in urban areas and
      Chinese ethnicity. The regional and racial difference is not so obvious in adult
      populations aged over 40 years. More time spent on near work, less time outdoors,
      higher educational level and parental history of myopia have been reported to
      increase the risk of myopia. CONCLUSIONS: Environmental factors play a crucial
      role in myopia development. The effect of gene-environment interaction on the
      aetiology of myopia is still controversial with inconsistent findings in
      different studies. A relatively hyperopic periphery can stimulate compensating
      eye growth in the centre. Longitudinal cohort studies or randomized clinical
      trials of community-based health behaviour interventions should be conducted to
      further clarify the aetiology of myopia.

PMID- 22150587
TI  - Prevalence of myopia among Hong Kong Chinese schoolchildren: changes over two
      decades.
AB  - PURPOSE: Studies have documented an increasing prevalence of myopia among
      urbanized Asian countries over recent decades. In the early 1990s, the reported
      prevalence rate was 25% and 64% for 6 and 12 year old children respectively. This
      cross-sectional study aims to determine the current prevalence of myopia amongst
      Hong Kong Chinese schoolchildren and whether there has been any increase over the
      last two decades. METHODS: Data from 2651 children aged 6-12 (mean age: 8.92 +/-
      1.77, 53% boys) who participated in vision screening during 2005-2010 were
      analyzed. Visual parameters including visual acuity (in logMAR) and binocular
      status under the participants' habitual correction were assessed. Refractive
      errors were examined using non-cycloplegic auto-refraction and axial lengths were
      measured by partial coherence interferometry. RESULTS: The mean spherical
      equivalent refraction for this population was -1.02 +/- 1.70D, ranging from +4.75
      to -10.00D. Prevalence of myopia (more than -0.50D) was 18.3% for the 6-year-old
      group and 61.5% for the 12-year-old group. Average myopia magnitude was -0.06 +/-
      1.03D at age 6 and -1.67 +/- 1.99D at age 12. Prevalence of high myopia of more
      than -6.00D was 1.8%, with an increase from 0.7% at the age of 6 to 3.8% at the
      age of 12. CONCLUSIONS: The prevalence of myopia among the Chinese schoolchildren
      population in Hong Kong as observed in this cross-sectional study are similar to
      our previously reported findings from almost two decades ago. There is no
      evidence that prevalence of myopia is increasing with time over the last two
      decades. However, the prevalence and degree of myopia in Chinese children is high
      as compared with other ethnic groups such as those reported among Caucasians.

PMID- 22150588
TI  - Common variants in chromosome 4q25 are associated with myopia in Chinese adults.
AB  - PURPOSE: A genome-wide association study (GWAS) of high myopia found that five
      single nucleotide polymorphisms (SNPs) in 4q25 were associated with high myopia.
      The original study suggested replication studies were needed to validate these
      results. The aim of our study was to examine if these SNPs are associated with
      myopia in a different set of samples. METHODS: Genomic DNA was collected from
      2307 unrelated individuals, including 1052 university students without myopia and
      1255 university students with myopia (615 students with moderate myopia and 640
      students with high myopia). Four of the five reported SNPs at 4q25, rs2218817,
      rs10034228, rs1585471 and rs6837348, were genotyped using SNaPshot. The genotype
      and allele frequencies of the SNPs between myopias and controls were compared by
      chi-squared test. RESULTS: Genotype and allele frequencies of the four SNPs
      showed significant differences between the myopia and control groups (rs2218817:
      genotype p = 0.009, OR = 1.18; rs10034228: genotype p = 0.009, OR = 1.18;
      rs1585471: genotype p = 0.007, OR = 1.19 and rs6837348: genotype p = 0.012, OR =
      1.18). CONCLUSIONS: Our results support the association between the four SNPs and
      myopia, suggesting a myopia predisposing locus at 4q25 that deserves further
      study.

PMID- 22150589
TI  - Solution structure of the Pdp1 PWWP domain reveals its unique binding sites for
      methylated H4K20 and DNA.
AB  - Methylation of H4K20 (Lys(20) of histone H4) plays an important role in the
      regulation of diverse cellular processes. In fission yeast, all three states of
      H4K20 methylation are catalysed by Set9. Pdp1 is a PWWP (proline-tryptophan
      tryptophan-proline) domain-containing protein, which associates with Set9 to
      regulate its chromatin localization and methyltransferase activity towards H4K20.
      The structure of the Pdp1 PWWP domain, which is the first PWWP domain identified
      which binds to methyl-lysine at the H4K20 site, was determined in the present
      study by solution NMR. The Pdp1 PWWP domain adopts a classical PWWP fold, with a
      five-strand antiparallel beta-barrel followed by three alpha-helices. However, it
      differs significantly from other PWWP domains in some structural aspects that
      account, in part, for its molecular recognition. Moreover, we revealed a unique
      binding pattern of the PWWP domain, in that the PWWP domain of Pdp1 bound not
      only to H4K20me3 (trimethylated Lys(20) of histone H4), but also to dsDNA (double
      stranded DNA) via an aromatic cage and a positively charged area respectively.
      EMSAs (electrophoretic mobility-shift assays) illustrated the ability of the Pdp1
      PWWP domain to bind to the nucleosome core particle, and further mutagenesis
      experiments indicated the crucial role of this binding activity in histone H4K20
      di- and tri-methylation in yeast cells. The present study may shed light on a
      novel mechanism of histone methylation regulation by the PWWP domain.

PMID- 22150596
TI  - Outpatient diagnostic of bladder tumours in flexible cystoscopes: evaluation of
      fluorescence-guided flexible cystoscopy and bladder biopsies.
AB  - OBJECTIVE: The aim of this study was to evaluate photodynamic diagnosis (PDD) in
      flexible cystoscopes and the diagnostic quality of biopsies for diagnosis of non
      muscle-invasive bladder cancer in the outpatients department (OPD). MATERIAL AND
      METHODS: Seventy-three patients (aged 36-91 years) with recurrent non-muscle
      invasive bladder cancer and a medium to high risk of recurrence had a flexible
      PDD cystoscopy performed in the OPD. The bladder was first examined in standard
      white light followed by PDD. RESULTS: PDD was superior to white light diagnosis;
      PDD was positive in 16 patients (22%) where white light showed a normal bladder
      mucosa. Four of these patients had bladder tumour [4/73, 6%; two carcinoma in
      situ (CIS), two Ta]. The diagnosis was verified by transurethral resection of the
      bladder tumour in the operating room. In 20 patients (20/73, 27%) PDD identified
      additional tumour lesions that were not identified in white light (five CIS, 15
      Ta). The false-positive detection rate of PDD was 0.41. False positivity was
      significantly reduced by simultaneous flex biopsies disproving malignancy.
      Biopsies were obtained from 57 patients and diagnosis of stage and grade were
      possible in 55 of these (97%). In two patients (4%) the tissue material was too
      small for diagnostic evaluation. Biopsies from 47 patients (83%) included
      muscularis mucosa and from 20 patients (35%) muscularis propria. In 30 patients
      all but one diagnosis from the OPD was confirmed by biopsy in rigid scopes in the
      operating room. CONCLUSIONS: PDD-guided cystoscopy and bladder biopsy in flexible
      cystoscopes can be performed in an OPD setting and with reliable results for
      diagnosis of tumour stage Ta, CIS and T1a bladder cancer.

PMID- 22150597
TI  - Irido-lenticular abscess as the initial sign of Candida albicans endogenous
      endophthalmitis.
AB  - A-33-year-old man presented with 9 days of conjunctival erythema, pain, and
      worsening vision in the left eye. Anterior segment examination was significant
      for a well-defined, cream-colored iridociliary mass. Ultrasound biomicroscopy
      demonstrated an iris lesion with ciliary body and lenticular involvement. The
      authors performed a pars plana vitrectomy and lensectomy with an iris biopsy.
      Culture of the vitreous cassette and iris mass yielded a diagnosis of Candida
      albicans endophthalmitis. Clinicians encountering an iris nodule with lenticular
      involvement, even in an immunocompetent adult, are urged to consider a diagnosis
      of an endogenous endophthalmitis secondary to C. albicans.

PMID- 22150598
TI  - Optical coherence tomography for retinal metastasis with unknown primary tumor.
AB  - The authors describe the optical coherence tomography (OCT) findings and the
      therapeutic approach of a patient with metastatic neoplastic disease of the
      retina. A patient with a history of brain cancer of undetermined origin underwent
      imaging and surgery to investigate a suspected metastatic retinal lesion of the
      right eye. Retinal thinning with cordon-like hyperreflective structures was seen
      on OCT. Neoplastic cells consistent with small cell carcinoma were identified in
      the vitreous sample. Those cells were thought to be similar to the previous
      biopsied cerebellar tumor specimen. OCT imaging, along with vitrectomy and
      retinal biopsy, may be useful in the evaluation of patients with suspected
      metastatic lesions of the retina.

PMID- 22150600
TI  - Spectral-domain optical coherence tomography of the choroid in choroidal osteoma.
AB  - The authors report spectral-domain optical coherence tomography (SD-OCT) findings
      in a patient with decalcifying choroidal osteoma accompanied by a choroidal
      neovascular membrane and serous retinal detachment. A 13-year-old girl was found
      to have a choroidal osteoma in the left eye. The clinical diagnosis was confirmed
      by B-scan ultrasonography, computed tomography, and fluorescein and indocyanine
      green angiography. The SD-OCT findings over the decalcified portion included
      serous retinal detachment, photoreceptor outer segment disorganization, retinal
      pigment epithelial atrophy, deformed Bruch's membrane, and choroidal neovascular
      membrane. In contrast, the retinal structures over the calcified portion appeared
      to be preserved. SD-OCT showed loss of a vascular appearance and increased
      thickness in the affected choroid, especially in the decalcified portion.
      Choroidal thickening may be associated not only with choroidal osteomas, but also
      with tumor decalcification. These unique features on SD-OCT may be important in
      understanding poor visual prognosis when decalcification involves the fovea.

PMID- 22150599
TI  - Efficacy of brinzolamide ophthalmic suspension 1% for treatment of a vitelliform
      macular lesion in a patient with desferrioxamine retinopathy.
AB  - A 46-year-old woman with a vitelliform macular lesion secondary to
      desferrioxamine retinal toxicity in the right eye was treated with brinzolamide
      1% ophthalmic drops three times a day. A spectral-domain optical coherence
      tomography (SD-OCT) unit was used to monitor any changes in the macular lesion.
      Two months after starting the eye drops, the SD-OCT showed a notable improvement
      in the vitelliform macular lesion's thickness. Six months later, further
      improvement was noted in the macular lesion thickness on SD-OCT testing in the
      right eye. Best-corrected visual acuity was initially 1.00 logarithm of the
      minimum angle of resolution (20/200 on a Snellen acuity chart) in the right eye
      and 0.14 logarithm of the minimum angle of resolution (20/25(-2)) in the left
      eye. After 6 months of treatment, visual acuity was 0.92 (20/200(+1)) in the
      right eye and 0.08 (20/25(+1)) in the left eye. The use of brinzolamide 1% was
      associated with a marked reduction in a vitelliform macular lesion on SD-OCT
      testing secondary to desferrioxamine retinal toxicity.

PMID- 22150601
TI  - Atypical presentation of Salzmann nodular degeneration diagnosed with ultra-high
      resolution optical coherence tomography.
AB  - A 59-year-old woman presented with bilateral, peripheral, circular corneal
      infiltrates. There was a clear zone separating the outer margin of the
      degeneration from the limbus in both eyes. The inner margins were indistinct.
      Ultra-high-resolution optical coherence tomography (UHR-OCT) imaging demonstrated
      subepithelial infiltrations with epithelial thinning and corneal surface
      elevation. The infiltrate was accompanied by significant stromal scarring, which
      reached deep layers of the corneal stroma. UHR-OCT findings were consistent with
      Salzmann nodular degeneration. UHR-OCT can be used as an optical biopsy to
      diagnose atypical corneal degenerations without tissue sampling.

PMID- 22150602
TI  - The surgical treatment of congenital tarsal kink syndrome associated with corneal
      ulcer.
AB  - The authors present a case of unilateral eyelid congenital tarsal kink associated
      with corneal ulcer. The tarsal kink was corrected by a horizontal tarsal
      incision, performed half the thickness of the tarsus along its entire horizontal
      extent. Terminal levator aponeurosis fibers were reattached to the tarsal
      incision line to create sufficient everting force for correction of the
      entropion. The tarsal kink disappeared and eyelid positions remained stable
      during a follow-up period of 2 years.

PMID- 22150603
TI  - Limbal lacuna: a novel limbal structure detected by in vivo laser scanning
      confocal microscopy.
AB  - Limbal lacuna is a novel limbal structure detected by in vivo laser scanning
      confocal microscopy in normal subjects and the unaffected limbus in sectoral
      limbal stem cell deficiency. This unique structure harbors normal limbal
      epithelial cells deep inside the limbal stroma and the palisades of the Vogt are
      absent in these subjects. This well-protected location could better shield limbal
      stem/progenitor cells from damage and might serve as an alternative niche for
      limbal stem/progenitor cells.

PMID- 22150604
TI  - Canine hip dysplasia: reviewing the evidence for nonsurgical management.
AB  - OBJECTIVE: To systematically review the evidence available for nonsurgical
      management of hip dysplasia (HD). STUDY DESIGN: Literature review. METHODS:
      Databases (Pubmed, Veterinary Information Network) were searched for clinical
      studies on nonsurgical management of HD in dogs. The evidence in each study was
      reviewed and assigned a score (I-IV) based on previously reported levels of
      evidence. RESULTS: Fourteen articles were identified that met the inclusion
      criteria, including 3 Level IV, 4 Level III, and 7 Level II studies. Methods of
      nonsurgical management reviewed included: activity restrictions, weight
      management, acupuncture, modulation of joint disease by polysulfated
      glycosaminoglycans, mesenchymal stem cell therapy, and extra corporeal shock wave
      therapy. CONCLUSION: Weight management is an effective and important component of
      managing dogs with HD and associated osteoarthritis. Techniques that modulate the
      progression of joint disease may also be beneficial for treating dogs with HD.
      Further studies are needed to investigate other methods of managing HD such as
      hydrotherapy and physical rehabilitation.

PMID- 22150605
TI  - Identification of forensically important flesh flies based on a shorter fragment
      of the cytochrome oxidase subunit I gene in China.
AB  - With the development of molecular identification, there has been a great deal of
      discussion about the feature of the mitochondrial DNA (mtDNA) fragments. Although
      longer fragments may minimize stochastic variation across taxa and be more likely
      to reflect broader patterns of nucleotide divergence, shorter fragments have many
      advantages, such as quick, easy and economical. Extensive application of long
      mtDNA segments for species identification cannot always be achieved as a result
      of constraints in time and money. In the present study, a molecular
      identification method involving the sequencing of a 272-bp 'barcode' fragment of
      the mitochondrial cytochrome oxidase subunit I (COI) gene from 55 specimens,
      representing 7 Chinese sarcophagid species from varying populations, was
      evaluated. Phylogenetic analysis of the sequenced segments showed that all
      sarcophagid specimens were properly assigned into seven species, which indicated
      the possibility of separation congeneric species with the short fragments. The
      results of this research will be instrumental for the implementation of the
      Chinese Sarcophagidae database.

PMID- 22150606
TI  - Gummed-up memory: chewing gum impairs short-term recall.
AB  - Several studies have suggested that short-term memory is generally improved by
      chewing gum. However, we report the first studies to show that chewing gum
      impairs short-term memory for both item order and item identity. Experiment 1
      showed that chewing gum reduces serial recall of letter lists. Experiment 2
      indicated that chewing does not simply disrupt vocal-articulatory planning
      required for order retention: Chewing equally impairs a matched task that
      required retention of list item identity. Experiment 3 demonstrated that manual
      tapping produces a similar pattern of impairment to that of chewing gum. These
      results clearly qualify the assertion that chewing gum improves short-term
      memory. They also pose a problem for short-term memory theories asserting that
      forgetting is based on domain-specific interference given that chewing does not
      interfere with verbal memory any more than tapping. It is suggested that tapping
      and chewing reduce the general capacity to process sequences.

PMID- 22150607
TI  - Underestimation of left atrial volume by three-dimensional echocardiography
      validated by magnetic resonance imaging: a meta-analysis and investigation of the
      source of bias.
AB  - BACKGROUND: Left atrial volume (LAV) is a fundamental prognostic factor in a
      variety of cardiac diseases including atrial fibrillation, heart failure, and
      valvular diseases. Developing a repeatable, noninvasive, and accurate method of
      measuring LAV is crucial. Three-dimensional echocardiography (3DE) has achieved
      better estimation of LAV than two-dimensional echocardiography. However,
      underestimation of LAV by 3DE has often been reported and no previous study has
      synthesized these data. The present study aimed at revealing existence and extent
      of bias in LAV measurement by 3DE and investigating related factors affecting the
      bias. METHODS: Studies comparing LAV between 3DE and magnetic resonance imaging
      published before August 15, 2011 were eligible. A meta-analysis with random
      effects model was performed to evaluate the systematic bias. Factors affecting
      the bias were investigated by univariate followed by multivariate analysis.
      RESULTS: A total of 14 studies including 395 subjects revealed underestimation of
      LAV by 3DE (-9.4 mL; 95% confidence interval, -13.2 to -5.6 mL; P < 0.00001, Fig.
      2). Existence of cardiac disease led to more underestimation, whereas increasing
      the number of plane included in the analysis counteracted the underestimation (P
      < 0.00001 for each comparison). CONCLUSIONS: Only by synthesizing a number of
      small studies as a meta-analysis could we display underestimation of LAV by 3DE
      and factors influencing the systematic bias. These data provide a more detailed
      basis for analyzing and improving the accuracy of 3DE, an indispensable step
      toward further clinical application in LAV assessment.

PMID- 22150608
TI  - A dynamic flux in natural killer cell subsets as a function of the duration of
      alcohol ingestion.
AB  - BACKGROUND: Chronic ethanol (EtOH) consumption is associated with a wide variety
      of immune abnormalities including changes in T cells, B cells, dendritic cells,
      and natural killer (NK) cells. However, there is conflicting information as to
      the direction of such immune changes. The hypothesis that was tested in this
      report is that, for NK cells, the changes can vary as a function of the duration
      of alcohol ingestion. METHODS: Using the Meadows-Cook murine model of chronic
      alcohol ingestion, the changes in NK cell function and subset distribution were
      examined as a function of the duration of alcohol ingestion. RESULTS: Acute
      alcohol ingestion resulted in decreased number and cytotoxic function of NK cells
      with no effect on intracellular interferon gamma expression. These abnormalities
      normalized after 12 to 14 days of alcohol ingestion and there was an increase of
      NK cell number and cytotoxicity after 8 weeks of continued EtOH ingestion. Ten
      weeks of continued alcohol consumption results in a significant decrease in the
      Ly49H+ CD11b+ CD27- splenic NK cell subset; this difference continued to be
      significant at 30 weeks. CONCLUSIONS: This report may explain some of the
      conflicting data in the literature that examined NK cell activity in alcoholic
      patients. It is apparent that various abnormalities can be seen in NK cell
      activity and subset distribution with the flux being a function of the duration
      of alcohol ingestion. The demonstration of a decrease in the Ly49H+ subset (which
      is known to be involved in resisting murine cytomegalovirus infection) may
      explain the reported increase in susceptibility to some viral infections in
      chronic alcohol abuse. Another novel finding is that changes of some subsets of
      NK cells are not evident until at least 10 weeks of continued EtOH consumption.

PMID- 22150609
TI  - Association between age, IL-10, IFNgamma, stimulated C-peptide and disease
      progression in children with newly diagnosed Type 1 diabetes.
AB  - AIMS: The relation of disease progression and age, serum interleukin 10 (IL-10)
      and interferon gamma (IFNgamma) and their genetic correlates were studied in
      paediatric patients with newly diagnosed Type 1 diabetes. METHODS: Two hundred
      and twenty-seven patients from the Hvidoere Study Group were classified in four
      different progression groups as assessed by change in stimulated C-peptide from 1
      to 6 months. CA repeat variants of the IL-10 and IFNgamma gene were genotyped and
      serum levels of IL-10 and IFNgamma were measured at 1, 6 and 12 months. RESULTS:
      IL-10 decreased (P < 0.001) by 7.7% (1 month), 10.4% (6 months) and 8.6% (12
      months) per year increase in age of child, while a twofold higher C-peptide
      concentration at 1 month (p = 0.06), 6 months (P = 0.0003) and 12 months (P =
      0.02) was associated with 9.7%, 18.6% and 9.7% lower IL-10 levels, independent of
      each other. IL-10 concentrations did not associate with the disease progression
      groups. By contrast, IFNgamma concentrations differed between the four
      progression groups at 6 and 12 months (P = 0.02 and P = 0.01, respectively);
      patients with rapid progressing disease had the highest levels at both time
      points. Distribution of IL-10 and IFNgamma genotypes was equal among patients
      from the progression groups. CONCLUSION: IL-10 serum levels associate inversely
      with age and C-peptide. As age and C-peptide also associate, a triangular
      association is proposed. Genetic influence on IL-10 production seems to be masked
      by distinct disease mechanisms. Increased serum IFNgamma concentrations associate
      with rapid disease progression. Functional genetic variants do not associate with
      a single progression pattern group, implying that disease processes override
      genetically predisposed cytokine production.

PMID- 22150612
TI  - Causal inference on quantiles with an obstetric application.
AB  - The current statistical literature on causal inference is primarily concerned
      with population means of potential outcomes, while the current statistical
      practice also involves other meaningful quantities such as quantiles. Motivated
      by the Consortium on Safe Labor (CSL), a large observational study of obstetric
      labor progression, we propose and compare methods for estimating marginal
      quantiles of potential outcomes as well as quantiles among the treated. By
      adapting existing methods and techniques, we derive estimators based on outcome
      regression (OR), inverse probability weighting, and stratification, as well as a
      doubly robust (DR) estimator. By incorporating stratification into the DR
      estimator, we further develop a hybrid estimator with enhanced numerical
      stability at the expense of a slight bias under misspecification of the OR model.
      The proposed methods are illustrated with the CSL data and evaluated in
      simulation experiments mimicking the CSL.

PMID- 22150614
TI  - Red blood cells, transfusion-related acute lung injury, and lipids: a role for
      liporeduction?

PMID- 22150615
TI  - Three doctors for a transfusion during World War I.

PMID- 22150617
TI  - Case report of eccrine porocarcinoma in situ associated with eccrine poroma on
      the forehead.

PMID- 22150618
TI  - HIV screening for pregnant women and infants.

PMID- 22150619
TI  - Extracellular deoxyribonuclease production by periodontal bacteria.
AB  - BACKGROUND AND OBJECTIVE: Whilst certain bacteria have long been known to secrete
      extracellular deoxyribonuclease (DNase), the purpose in microbial physiology was
      unclear. Recently, however, this enzyme has been demonstrated to confer enhanced
      virulence, enabling bacteria to evade the host's immune defence of extruded
      DNA/chromatin filaments, termed neutrophil extracellular traps (NETs). As NETs
      have recently been identified in infected periodontal tissue, the aim of this
      study was to screen periodontal bacteria for extracellular DNase activity.
      MATERIAL AND METHODS: To determine whether DNase activity was membrane bound or
      secreted, 34 periodontal bacteria were cultured in broth and on agar plates.
      Pelleted bacteria and supernatants from broth cultures were analysed for their
      ability to degrade DNA, with relative activity levels determined using an agarose
      gel electrophoresis assay. Following culture on DNA-supplemented agar, expression
      was determined by the presence of a zone of hydrolysis and DNase activity related
      to colony size. RESULTS: Twenty-seven bacteria, including red and orange complex
      members Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum,
      Parvimonas micra, Prevotella intermedia, Streptococcus constellatus,
      Campylobacter rectus and Prevotella nigrescens, were observed to express
      extracellular DNase activity. Differences in DNase activity were noted, however,
      when bacteria were assayed in different culture states. Analysis of the activity
      of secreted DNase from bacterial broth cultures confirmed their ability to
      degrade NETs. CONCLUSION: The present study demonstrates, for the first time,
      that DNase activity is a relatively common property of bacteria associated with
      advanced periodontal disease. Further work is required to determine the
      importance of this bacterial DNase activity in the pathogenesis of periodontitis.

PMID- 22150620
TI  - Lactate levels predict mortality and need for peritoneal dialysis in children
      undergoing congenital heart surgery.
AB  - BACKGROUND: The purpose of this study was to investigate whether an initial post
      operative lactate level is a predictor of mortality, need for peritoneal dialysis
      (PD), duration of intubation or length of stay (LOS) in the intensive care unit
      (ICU) in children undergoing cardiac surgery. METHOD: A retrospective,
      observational follow-up study was conducted in 206 children undergoing cardiac
      surgery from 2006 to 2007. Multivariate logistics regression analyses were
      performed to determine whether the lactate level was an independent risk factor.
      The lactate concentration at arrival in the ICU, outcome and risk factors
      (patient demographics, surgical complexity, duration of cardiopulmonary bypass
      and inotropic score) were obtained from the electronic patient data management
      program and medical records. RESULT: The median (interquartile range) lactate
      level was 1.9 mmol/l (1.3-2.7) in children immediately after cardiac surgery and
      a mortality of 3.9%. Eight percent of the children had a lactate level higher
      than 4.5 mmol/l. An increased lactate level >=4.5 mmol/l resulted in an odds
      ratio (95% confidence intervals) of 8.4 (1.5-46.1) for mortality and an odds
      ratio of 16.9 (2.7-106.8) for PD after adjusting for Risk Adjustment for
      Congenital Heart Surgery 1. Because of the low number of deaths, limited
      confounder analysis was performed. Duration of intubation and LOS in the ICU were
      not associated with the initial lactate level when adjusting for confounders.
      CONCLUSION: The initial post-operative lactate level was a predictor of mortality
      and need for PD in children undergoing surgery for congenital heart disease.

PMID- 22150621
TI  - Recreational drug misuse and stroke.
AB  - Stroke is the third commonest cause of death and single largest cause of adult
      disability worldwide. Whilst the majority of strokes in older individuals are due
      to large or small vessel arterial disease or cardiac disease in association with
      classical vascular risk factors, strokes occurring in younger individuals may
      have atypical etiologies. Recreational substance misuse is on the increase
      worldwide, particularly in young adults in developed countries with commonly used
      substances including cocaine, amphetamines, heroin and other opiates, marijuana
      and gammahydroxybutyrate (GHB). Adverse vascular sequelae of inappropriate use of
      these substances is well recognized but the link between acute stroke and
      substance misuse is often underestimated. Both ischemic and hemorrhagic strokes
      may be caused by recreational substance misuse and this paper reviews the
      available evidence and discusses the potential pathophysiological links.

PMID- 22150622
TI  - Increasing delta-9-tetrahydrocannabinol (Delta-9-THC) content in herbal cannabis
      over time: systematic review and meta-analysis.
AB  - AIM: The objective of this meta-analysis is to assess the data regarding changes
      in herbal cannabis potency over time (from 1970 to 2009). METHODS: Systematic
      searches of 17 electronic scientific databases identified studies on this topic,
      within which 21 case series studies satisfied our inclusion criteria of reporting
      the mean tetrahydrocannabinol (THC) value per number of samples per year. No
      language, publication date, publication type or status restrictions were imposed.
      The study selection and data extraction processes were performed independently
      but uniformly by two authors, included screening, determination of eligibility
      and inclusion of the eligible studies in the systematic review, and a meta
      analysis of the results on THC content in herbal cannabis samples. We considered
      papers and not monographic scientific publications, rejecting all studies that
      were not focused on the subject of this review. RESULTS: Meta-analysis by year
      was performed on 21 studies containing 75 total mean THC observations from 1979
      to 2009 using the random effects model. The results revealed much variability
      between studies. Further, there was a significant correlation between year and
      mean THC in herbal cannabis. The combined data indicated the correlation between
      year and mean THC in herbal cannabis, revealing a temporal trend of increasing
      potency (5% above the mean THC value in the Poisson regression analysis).
      CONCLUSIONS: The results of the analysis suggest that there has been a recent and
      consistent increase in cannabis potency worldwide.

PMID- 22150623
TI  - Cannabinoid hyperemesis syndrome.
AB  - Coinciding with the increasing rates of cannabis abuse has been the recognition
      of a new clinical condition known as Cannabinoid Hyperemesis Syndrome.
      Cannabinoid Hyperemesis Syndrome is characterized by chronic cannabis use, cyclic
      episodes of nausea and vomiting, and frequent hot bathing. Cannabinoid
      Hyperemesis Syndrome occurs by an unknown mechanism. Despite the well-established
      anti-emetic properties of marijuana, there is increasing evidence of its
      paradoxical effects on the gastrointestinal tract and CNS. Tetrahydrocannabinol,
      cannabidiol, and cannabigerol are three cannabinoids found in the cannabis plant
      with opposing effects on the emesis response. The clinical course of Cannabinoid
      Hyperemesis Syndrome may be divided into three phases: prodromal, hyperemetic,
      and recovery phase. The hyperemetic phase usually ceases within 48 hours, and
      treatment involves supportive therapy with fluid resuscitation and anti-emetic
      medications. Patients often demonstrate the learned behavior of frequent hot
      bathing, which produces temporary cessation of nausea, vomiting, and abdominal
      pain. The broad differential diagnosis of nausea and vomiting often leads to
      delay in the diagnosis of Cannabinoid Hyperemesis Syndrome. Cyclic Vomiting
      Syndrome shares several similarities with CHS and the two conditions are often
      confused. Knowledge of the epidemiology, pathophysiology, and natural course of
      Cannabinoid Hyperemesis Syndrome is limited and requires further investigation.

PMID- 22150625
TI  - HER2 status in primary stage T1 urothelial cell carcinoma of the urinary bladder.
AB  - OBJECTIVE: The HER2 receptor is involved in pathways essential for cell
      proliferation, and is an important predictive and prognostic factor in breast
      cancer. HER2 probably plays a critical role in many types of cancer, including
      urothelial carcinoma of the bladder (UCB). Stage T1 UCB exhibits heterogeneous
      clinical behaviour, and the frequency of HER2 expression in such disease has not
      been thoroughly examined. The aim of this study was to use an immunohistochemical
      technique to evaluate the frequency of HER2 expression in a defined population
      based cohort of patients registered as having primary stage T1 UCB. MATERIAL AND
      METHODS: The initial study population comprised 285 patients registered as having
      primary stage T1 UCB. The original histological specimens were re-evaluated with
      regard to T stage and World Health Organization grade. Hospital records provided
      information on tumour size, multiplicity, possible presence of histologically
      proven recurrence and progression. The patients were followed for at least 5
      years or until death. In tumours still considered stage T1 after re-evaluation,
      HER2 was investigated by immunohistochemistry of paraffin-embedded material and
      scored according to the guidelines used in breast cancer. RESULTS: After
      histopathological re-evaluation, 201 patients were still T1 UCB and could be
      investigated regarding HER2 expression. HER2 overexpression was observed in 25 of
      those patients (12.4%). HER2 status was not significantly associated with
      recurrence or progression. CONCLUSIONS: HER2 was overexpressed in 12.4% of the
      present cohort of patients with primary stage T1 UCB. There was no significant
      association between tumour HER2 status and prognosis.

PMID- 22150624
TI  - Alcoholism, personality, and religion/spirituality: an integrative review.
AB  - A review of the literature on the relationships between alcoholism, personality,
      and religion identified patterns that may help explain the inverse association
      between alcoholism and religion/spirituality (R/S). Personality plays a central
      role in two etiological models of alcoholism. The personality traits of high
      behavioral undercontrol (low Agreeableness and low Conscientiousness) and high
      negative affect (high Neuroticism) are both significantly related to higher
      alcohol use. Religiosity is also correlated with these traits, but in the
      opposite direction (e.g., with low behavioral undercontrol and low negative
      affect). Thus, the personality profiles associated with alcoholism and religion
      are the inverse of one another. In addition, evidence suggests that R/S moderates
      genetic variation on both Neuroticism and Disinhibition (part of behavioral
      undercontrol). Implications are discussed in terms of competing explanatory
      models: a basic research model which argues for genetically-determined stability
      in personality and alcoholism risk, and a clinical treatment model which argues
      for the primacy of environmental interventions in treatment and the possibility
      of personality change as a pathway to recovery.

PMID- 22150626
TI  - Management of an extremely premature infant in the out-of-hospital environment.
AB  - The rate of premature infant mortality has decreased over the last several
      decades, with an accompanying decrease in the gestational age of premature
      infants who survive to hospital discharge. Emergency medical services (EMS)
      providers are sometimes called to provide prehospital care for infants born at
      the edge of viability. Such extremely premature infants (EPIs) present medical
      and ethical challenges. In this case report, we describe an infant born at 24
      weeks into a toilet by a mother who thought she had miscarried. The EMS providers
      evaluated the infant as nonviable and placed him in a plastic bag for transport
      to a local emergency department (ED). The ED staff found the infant to have a
      bradycardic rhythm, initiated resuscitation, and admitted him to the neonatal
      intensive care unit. The infant died seven days later. We review the literature
      for recommendations in resuscitation of EPIs and discuss the ethics regarding
      their management in the prehospital setting.

PMID- 22150627
TI  - Minimum nurse staffing legislation and the financial performance of California
      hospitals.
AB  - OBJECTIVE: To estimate the effect of minimum nurse staffing ratios on California
      acute care hospitals' financial performance. DATA SOURCES/STUDY SETTING:
      Secondary data from Medicare cost reports, the American Hospital Association's
      (AHA) Annual Survey, and the California Office of Statewide Health Planning and
      Development (OSHPD) are combined from 2000 to 2006 for 203 hospitals in
      California and 407 hospitals in 12 comparison states. STUDY DESIGN: The study
      employs a difference-in-difference analytical approach. Hospitals are grouped
      into quartiles based on pre-regulation nurse staffing levels in adult medical
      surgical and pediatric units (quartile 1=lowest staffing). Differences in
      operating margin, operating expenses per day, and inpatient operating expenses
      per discharge for California hospitals within a staffing quartile during the
      period of regulation are compared to differences at hospitals in comparison
      states during the same period. DATA COLLECTION/EXTRACTION METHODS: Hospital data
      from Medicare cost reports are merged with nurse staffing measures obtained from
      AHA and from OSPHD. PRINCIPAL FINDINGS: Relative to hospitals in comparison
      states, operating margins declined significantly for California hospitals in
      quartiles 2 and 3. Operating expenses increased significantly in quartiles 1, 2,
      and 3. CONCLUSIONS: Implementation of minimum nurse staffing legislation in
      California put substantial financial pressure on some hospitals.

PMID- 22150628
TI  - Schmorl's nodes in an American military population: frequency, formation, and
      etiology.
AB  - This research investigates the frequency of Schmorl's nodes in differing
      populations, with new data from a skeletal sample from the Central Identification
      Laboratory (CIL) at the Joint Prisoner of War/Missing in Action Accounting
      Command, while also reviewing the etiology of Schmorl's node formation. Processes
      implicated in Schmorl's node formation include trauma, old age, disease,
      intrinsic abnormalities, and biomechanical factors, and they correlate with
      Schmorl's node formation to varying degrees. A survey of research from the
      anthropology and medical literature revealed Schmorl's node population
      frequencies ranging from 8 to 80%. The current study consists of two samples, one
      derived from CIL case reports and one analyzing skeletal remains. The case report
      sample yielded a Schmorl's node frequency of 19.8%. The examined sample yielded a
      frequency of 73.7%. The disparate frequencies reported are likely due mainly to
      differences in completeness and observability. It is likely that trauma was a
      major factor in the formation of Schmorl's nodes in the CIL study.

PMID- 22150629
TI  - Kindling-induced asymmetric accumulation of hippocampal 7S SNARE complexes
      correlates with enhanced glutamate release.
AB  - PURPOSE: To correlate kindling-associated alterations of the neurotransmitter
      secretory machinery, glutamate release in the trisynaptic hippocampal excitatory
      pathway, and the behavioral evolution of kindling-induced epileptogenesis.
      METHOD: Neurotransmitter release requires the fusion of vesicle and plasma
      membranes; it is initiated by formation of a stable, ternary complex (7SC) of
      SNARE [soluble N-ethylmaleimide sensitive factor (NSF) attachment protein
      receptor] proteins. Quantitative Western blotting was used to monitor levels of
      7SC and SNARE regulators [NSF, SV2 (synaptic vesicle protein 2)] in hippocampal
      synaptosomes from amygdala-kindled animals. Hippocampal synaptic glutamate
      release was measured in vivo with a unique microelectrode array (MEA) that uses
      glutamate oxidase to catalyze the breakdown of glutamate into a reporter
      molecule. KEY FINDINGS: Ipsilateral hippocampal accumulation of 7SC developed
      with onset of amygdalar kindling, but became permanent only in animals stimulated
      to at least Racine stage 3; the ratio peaked and did not increase with more than
      two consecutive stage 5 seizures. Chronic 7SC asymmetry was seen in entorhinal
      cortex and the hippocampal formation, particularly in dentate gyrus (DG) and CA1,
      but not in the other brain areas examined. There was a strong correlation between
      asymmetric 7SC accumulation and increased total hippocampal SV2. Following a 30
      day latent period, amplitudes of spontaneous synaptic glutamate release were
      enhanced in ipsilateral DG and reduced in ipsilateral CA3 of kindled animals;
      increased volleys of synaptic glutamate activity were seen in ipsilateral CA1.
      SIGNIFICANCE: Amygdalar kindling is associated with chronic changes in the flow
      of glutamate signaling in the excitatory trisynaptic pathway and with early but
      permanent changes in the mechanics of vesicular release in ipsilateral
      hippocampal formation.

PMID- 22150630
TI  - Human-protein-derived peptides for intracellular delivery of biomolecules.
AB  - Access of therapeutic biomolecules to cytoplasmic and nuclear targets is hampered
      by the inability of these molecules to cross biological membranes. Approaches to
      overcome this hurdle involve CPPs (cell-penetrating peptides) or protein
      transduction domains. Most of these require rather high concentrations to elicit
      cell-penetrating functionality, are non-human, pathogen-derived or synthetic
      entities, and may therefore not be tolerated or even immunogenic. We identified
      novel human-protein-derived CPPs by a combination of in silico and experimental
      analyses: polycationic CPP candidates were identified in an in silico library of
      all 30-mer peptides of the human proteome. Of these peptides, 60 derived from
      extracellular proteins were evaluated experimentally. Cell viability and siRNA
      (small interfering RNA) transfection assays revealed that 20 out of the 60
      peptides were functional. Three of these showed CPP functionality without
      interfering with cell viability. A peptide derived from human NRTN (neurturin),
      which contains an alpha-helix, performed the best in our screen and was uniformly
      taken up by cultured cells. Examples for payloads that can be delivered to the
      cytosol by the NRTN peptide include complexed siRNAs and both N- and C-terminally
      fused pro-apoptotic peptides.

PMID- 22150631
TI  - The effects of induced oblique astigmatism on symptoms and reading performance
      while viewing a computer screen.
AB  - INTRODUCTION: Computer vision syndrome (CVS) is a complex of eye and vision
      problems related to computer use which has been reported in up to 90% of computer
      users. Ocular symptoms may include asthenopia, accommodative and vergence
      difficulties and dry eye. Previous studies have reported that uncorrected
      astigmatism may have a significant impact on symptoms of CVS. However, its effect
      on task performance is unclear. METHODS: This study recorded symptoms after a 10
      min period of reading from a computer monitor either through the habitual
      distance refractive correction or with a supplementary -1.00 or -2.00D oblique
      cylinder added over these lenses in 12 young, visually-normal subjects.
      Additionally, the distance correction condition was repeated to assess the
      repeatability of the symptom questionnaire. Subjects' reading speed and accuracy
      were monitored during the course of the 10 min trial. RESULTS: There was no
      significant difference in reading rate or the number of errors between the three
      astigmatic conditions. However, a significant change in symptoms was reported
      with the median total symptom scores for the 0, 1 and 2D astigmatic conditions
      being 2.0, 6.5 and 40.0, respectively (p < 0.0001). Further, the repeatability
      coefficient of the total symptom score following the repeated zero astigmatism
      condition was +/- 13.46. CONCLUSIONS: The presence of induced astigmatism
      produced a significant increase in post-task symptoms but did not affect reading
      rate or the number of reading errors. The correction of small astigmatic
      refractive errors may be important in optimizing patient comfort during computer
      operation.

PMID- 22150632
TI  - High prevalence of hypovitaminosis D among pregnant women in southeast China.

PMID- 22150633
TI  - Measurement of effective aortic valve area using three-dimensional
      echocardiography in children undergoing aortic balloon valvuloplasty for aortic
      stenosis.
AB  - AIMS: Pressure gradient is used for timing of balloon aortic valvuloplasty for
      aortic stenosis (AS) in children, but does not correlate well with outcome and is
      limited if ventricular function is poor. In adults, effective orifice area (EOA)
      is used to assess AS severity, but EOA by continuity equation or 2D echo is
      unreliable in children. Three-dimensional echocardiography (3DE) may reliably
      assess EOA but has not been studied in children. We assessed measurement of
      aortic valve EOA by 3DE in children with AS before and after balloon aortic
      valvuloplasty and compared results with change in aortic valve gradient. METHODS:
      3DE was performed at time of catheterization before and after balloon aortic
      valvuloplasty. Using 3DE multiplanar review mode, valve annulus diameter, area,
      and EOA were measured and compared with change in aortic gradient and degree of
      aortic insufficiency. RESULTS: Twenty-four 3DE studies in 12 children (mean age
      4.4 +/- 5.0 years) were analyzed. EOA was measurable in all. Catheter peak
      gradient decreased from 45 +/- 10 to 26 +/- 17 mmHg (P = 0.0018). 3DE EOA
      increased after balloon aortic valvuloplasty (0.59 +/- 0.52 cm(2) vs 0.80 +/-
      0.70 cm(2) ; P = 0.03), without change in valve diameter. EOA change correlated
      with change in peak (r = 0.77; P = 0.005) and mean (r = 0.60; P = 0.03) aortic
      valve gradient post balloon aortic valvuloplasty. CONCLUSION: 3DE facilitates EOA
      measurement in pediatric AS and correlates with change in aortic valve gradient
      after balloon valvuloplasty.

PMID- 22150634
TI  - An efficacy study of a combined parent and teacher management training programme
      for children with ADHD.
AB  - BACKGROUND: Several parent training programmes and behavioural teacher training
      programmes built on learning theory have been developed for problem prevention
      and treatment of attention-deficit/hyperactivity disorder (ADHD) and/or
      oppositional defiant disorder (ODD) during the last few decades. Group format has
      often been used for parent training but single-subject designs are more common in
      teacher training. More studies have focussed on pre-school children than on older
      children, and a minority have been conducted in public mental health settings.
      AIM: This study aimed to evaluate a combined parent and teacher manual-based
      group training programme for children with ADHD conducted by the staff at a child
      and adolescent psychiatric clinic in Sweden. METHOD: The intervention was a
      modified version of Barkley's programme. Children were randomized to an
      Intervention or a Control group. Sixty-one parents and 68 teachers answered
      questions about ADHD and ODD symptoms, and about behavioural problems when the
      study started and at a 3-month follow-up. RESULTS: RESULTS showed that the
      intervention resulted in a reduction of the number of children who met DSM-IV
      criteria for ADHD and/or ODD. Effects were more pronounced in the home setting
      than in the school setting, and were further accentuated when both parents and
      teachers of the same child took part in the intervention. Teachers with more
      problematic classroom situations benefited most from the intervention.
      CONCLUSION: The programme, "Strategies in Everyday Life", has, in a regular
      clinical setting, demonstrated promising effects on children's disruptive
      behaviour, and a clinical implication was to recommend involving both parents and
      teachers in the programme.

PMID- 22150635
TI  - A flexible two-dimensional mortality model for use in indirect estimation.
AB  - Mortality estimates for many populations are derived using model life tables,
      which describe typical age patterns of human mortality. We propose a new system
      of model life tables as a means of improving the quality and transparency of such
      estimates. A flexible two-dimensional model was fitted to a collection of life
      tables from the Human Mortality Database. The model can be used to estimate full
      life tables given one or two pieces of information: child mortality only, or
      child and adult mortality. Using life tables from a variety of sources, we have
      compared the performance of new and old methods. The new model outperforms the
      Coale-Demeny and UN model life tables. Estimation errors are similar to those
      produced by the modified Brass logit procedure. The proposed model is better
      suited to the practical needs of mortality estimation, since both input
      parameters are continuous yet the second one is optional.

PMID- 22150636
TI  - Evaluation of txt2MEDLINE and development of short messaging service-optimized,
      clinical practice guidelines in Botswana.
AB  - OBJECTIVE: Currently clinicians in sub-Saharan Africa have limited access to the
      Internet, whereas mobile phone access and use is extensive. The University of
      Pennsylvania in collaboration with the National Library of Medicine launched
      txt2MEDLINE, a short messaging service (SMS) query of PubMed/MEDLINE, and SMS
      optimized clinical guidelines in Botswana. The objective of this project was to
      establish and evaluate the utility of these tools for clinicians in Botswana.
      MATERIALS AND METHODS: A local server was established at the University of
      Botswana that allowed clinicians to send queries and receive results via local
      (in-country) SMS text messaging on any type of cellular phone. The queries sent
      via txt2MEDLINE were returned as abbreviated "the bottom line" summaries of
      abstracts. The 2007 Botswana Treatment Guide was converted into a format that can
      be queried by SMS. Various types of healthcare workers were recruited to use and
      evaluate these services. RESULTS: Seventy-six healthcare workers attended
      training sessions for these services. In the preusage survey, most said they
      would use the services daily or weekly. During a 4-week trial period, use of
      these services dropped off dramatically. Participant feedback was collected and
      indicated that improvements in ease of use would increase the usage. CONCLUSIONS:
      This pilot project enables clinicians to query and receive PubMed abstract
      summaries and country-specific clinical guidelines using mobile phones. Feedback
      offers insight on how to improve this technology so that it can be adopted for
      long-term use. With further adjustments, these resources may provide an effective
      working model for other countries where limited Internet access impedes upon
      patient care.

PMID- 22150637
TI  - Data integrity module for data quality assurance within an e-health system in sub
      Saharan Africa.
AB  - OBJECTIVE: Ensuring good data quality within telemedicine and e-health systems in
      developing countries is resource intensive. We set out to evaluate an approach
      where in-built functionality within an electronic record system could identify
      data quality and integrity problems with little human input. MATERIALS AND
      METHODS: We developed a robust data integrity module to identify, enumerate, and
      facilitate correction of errors within an e-health system that is in wide use in
      sub-Saharan Africa. RESULTS: The data integrity module was successfully
      implemented within an electronic medical record system in Western Kenya. Queries
      were set to fail if one of more records did not meet defined criteria for data
      integrity. Only one of 14 data integrity checks implemented uncovered no errors.
      The other queries had errors or questionable results ranging from 51 records to
      30,301 records. However, as a proportion of all patients and all observation, the
      identified records with likely data integrity problems only constituted a small
      percentage of all records (mean 0.96%, range 0-4.1%). Twelve of the 14 queries
      (86%) were executed in<15 s, with the longest query lasting 2 min and 18 s.
      CONCLUSION: A tool that allows for automatic data integrity and quality checks
      was successfully implemented within an e-health system in sub-Saharan Africa. The
      tool potentially reduces the burden of maintaining data quality by limiting the
      scale of manual reviews needed to identify electronic records with errors.

PMID- 22150639
TI  - Synergism between ammonia and phenols for Hybomitra tabanids in northern and
      temperate Canada.
AB  - Baits for tabanids (Diptera: Tabanidae) were tested in the Northwest Territories
      (60  degrees N) and Ontario (45  degrees N) using Nzi traps. Tests targeted
      ammonia, phenols/cow urine and octenol. About 200 000 tabanids were captured in
      15 experiments with a maximum capture of 4182 in one trap in 1 day. In the
      Northwest Territories, phenols, urine and octenol were effective single baits for
      only some species. At both locations, adding ammonia to an unbaited or an octenol
      baited trap had no effect on catches. By contrast, catches were increased for
      several species when ammonia was combined with phenols or urine. In Ontario,
      including ammonia in various baits increased catches by 1.5- to 3.4-fold relative
      to octenol alone for three Hybomitra and one Tabanus species. Synergism between
      ammonia and phenols was clearly demonstrated for the dominant Hybomitra species
      in Ontario (Hybomitra lasiophthalma), but not for the dominant species in the
      Northwest Territories (Hybomitra epistates). In five other northern Hybomitra
      species, baits of ammonia and/or octenol in combination with phenols resulted in
      a 1.7- to 4.1-fold increase in catch relative to an unbaited trap. Further tests
      of ammonia as a synergist for biting flies may prove useful in, for example,
      tsetse, which respond strongly to phenols.

PMID- 22150638
TI  - Predicting medical staff intention to use an online reporting system with
      modified unified theory of acceptance and use of technology.
AB  - Barriers to report incident events using an online information system (IS) may be
      different from those of a paper-based reporting system. The nationwide online
      Patient-Safety Reporting System (PSRS) contains a value judgment behind use of
      the system, similar to the Value of Perceived Consequence (VPC), which is seldom
      discussed in ISs applications of other disciplines. This study developed a more
      adequate research framework by integrating the VPC construct into the well-known
      Unified Theory of Acceptance and Use of Technology (UTAUT) model as a theoretical
      base to explore the predictors of medical staff's intention to use online PSRS.
      The results showed that management support was an important factor to influence
      medical staff's intention of using PSRS. The effects of factors such as
      performance expectancy, perceived positive, and perceived negative consequence on
      medical staff's intention of using PSRS were moderated by gender, age,
      experience, and occupation. The results proved that the modified UTAUT model is
      significant and useful in predicting medical staff's intention of using the
      nationwide online PSRS.

PMID- 22150640
TI  - What happens after discharge? An analysis of long-term survival in cardiac
      surgical patients requiring prolonged intensive care.
AB  - BACKGROUND: Cardiac surgical patients with postoperative complications frequently
      require prolonged intensive care yet survive to hospital discharge. METHODS: From
      January 1, 2002 to December 31, 2007, 11,541 consecutive patients underwent
      cardiac operations at a single academic institution. Of these, 11,084 (95.9%)
      survived to hospital discharge and comprised the study sample. Patients were
      retrospectively categorized into four groups according to intensive care unit
      (ICU) length of stay (LOS): <3 days, three to seven days, 7 to 14 days, and >14
      days. Survival at 12 months was determined using the Social Security Death Index.
      Kaplan-Meier (KM) survival curves and Cox proportional hazards regression
      modeling (hazard ratio, HR) were used to analyze group differences in survival.
      RESULTS: One-year survival among the four groups according to ICU LOS was: <3
      days, 97.0% (8407/8666); three to seven days, 91.2% (1481/1625); 7 to 14 days,
      87.9% (356/405); and >14 days, 68.3% (265/388) (p < 0.001). Using multivariable
      regression analysis, adjusted overall mortality was significantly greater in
      patients with ICU LOS of three to seven days (HR = 1.51), 7 to 14 days (HR =
      1.40), and >14 days (HR = 1.90) compared to patients with ICU LOS <3 days.
      Mortality among patients who survived more than six months postsurgery was
      significantly greater in patients with ICU LOS of three to seven days (HR =
      1.37), 7 to 14 days (HR = 1.34), and >14 days (HR = 1.63). CONCLUSIONS: Although
      cardiac surgery patients with major postoperative complications frequently
      survive to hospital discharge, survival after discharge is significantly reduced
      in patients requiring prolonged ICU care. Reduced survival in patients with a
      high risk of complications and anticipated long ICU stays should be considered
      when discussing surgical versus nonsurgical options.

PMID- 22150641
TI  - Usefulness of margin detection by digital dermoscopy in the traditional surgical
      excision of basal cell carcinomas of the head and neck including
      infiltrative/morpheaform type.
AB  - Incomplete or suboptimal surgical excision of basal cell carcinoma of the head
      and neck is a relatively frequent occurrence. Methods of preoperative assessment
      of tumoral margins are therefore of paramount importance. The aim of this study
      was to compare the preoperative evaluation of margins with digital dermoscopy and
      clinical definition. One hundred and 12 patients with histologically confirmed
      basal cell carcinoma were selected for surgical excision. Subsequently, the
      margin of excision was determined by either clinical (45 patients) or dermoscopic
      evaluation (67 patients). After pre-surgical clinical evaluation, 22% of
      histological specimens of excised basal cell carcinoma showed suboptimal margins
      of excision. Pre-surgical dermoscopic evaluation had only 7% suboptimal excision.
      Preoperative digital dermoscopy is a better method to determine tumoral margins
      than clinical evaluation alone. Indeed, preoperative digital dermoscopy is an
      effective, simple, non-invasive procedure for the pre-surgical determination of
      margins.

PMID- 22150642
TI  - The effect of rising vs. falling glucose level on amperometric glucose sensor lag
      and accuracy in Type 1 diabetes.
AB  - BACKGROUND: Because declining glucose levels should be detected quickly in
      persons with Type 1 diabetes, a lag between blood glucose and subcutaneous sensor
      glucose can be problematic. It is unclear whether the magnitude of sensor lag is
      lower during falling glucose than during rising glucose. METHODS: Initially, we
      analysed 95 data segments during which glucose changed and during which very
      frequent reference blood glucose monitoring was performed. However, to minimize
      confounding effects of noise and calibration error, we excluded data segments in
      which there was substantial sensor error. After these exclusions, and combination
      of data from duplicate sensors, there were 72 analysable data segments (36 for
      rising glucose, 36 for falling). We measured lag in two ways: (1) the time delay
      at the vertical mid-point of the glucose change (regression delay); and (2)
      determination of the optimal time shift required to minimize the difference
      between glucose sensor signals and blood glucose values drawn concurrently.
      RESULTS: Using the regression delay method, the mean sensor lag for rising vs.
      falling glucose segments was 8.9 min (95%CI 6.1-11.6) vs. 1.5 min (95%CI -2.6 to
      5.5, P<0.005). Using the time shift optimization method, results were similar,
      with a lag that was higher for rising than for falling segments [8.3 (95%CI 5.8
      10.7) vs. 1.5 min (95% CI -2.2 to 5.2), P<0.001]. Commensurate with the lag
      results, sensor accuracy was greater during falling than during rising glucose
      segments. CONCLUSIONS: In Type 1 diabetes, when noise and calibration error are
      minimized to reduce effects that confound delay measurement, subcutaneous glucose
      sensors demonstrate a shorter lag duration and greater accuracy when glucose is
      falling than when rising.

PMID- 22150643
TI  - Effect of complete denture wearing on deglutition time: a cine-magnetic resonance
      imaging study.
AB  - Purpose of the study was to evaluate the effect of complete denture wearing on
      deglutition time (DT), hyoid bone and larynx movements in edentulous patients
      with real-time balanced turbo field echo cine-magnetic resonance imaging.
      Subjects were examined by cine-magnetic resonance imaging in supine position
      during swallowing water. Two sets of images for 23 edentulous (with/without
      wearing complete dentures) and one for 23 dentulous patients were obtained.
      Radiographic outputs representing three consecutive deglutition stages (oral,
      pharyngeal and oesophageal) were provided to perform measurements. Deglutition
      time significantly increased when edentulous patients wore their dentures (mean
      0.75 s increased to 1.17 s), whereas dentulous patients' DT was about 0.91 s (P
      <= 0.05). The duration of deglutition is crucial because prolonged pharyngeal
      transit times increases the risk of aspiration. Within the limitations of the
      study, complete denture wearing could increase the shortened DT of the edentulous
      patients.

PMID- 22150644
TI  - Rapid testing of SNPs and gene-environment interactions in case-parent trio data
      based on exact analytic parameter estimation.
AB  - Case-parent trio studies concerned with children affected by a disease and their
      parents aim to detect single nucleotide polymorphisms (SNPs) showing a
      preferential transmission of alleles from the parents to their affected
      offspring. A popular statistical test for detecting such SNPs associated with
      disease in this study design is the genotypic transmission/disequilibrium test
      (gTDT) based on a conditional logistic regression model, which usually needs to
      be fitted by an iterative procedure. In this article, we derive exact closed-form
      solutions for the parameter estimates of the conditional logistic regression
      models when testing for an additive, a dominant, or a recessive effect of a SNP,
      and show that such analytic parameter estimates also exist when considering gene
      environment interactions with binary environmental variables. Because the genetic
      model underlying the association between a SNP and a disease is typically
      unknown, it might further be beneficial to use the maximum over the gTDT
      statistics for the possible effects of a SNP as test statistic. We therefore
      propose a procedure enabling a fast computation of the test statistic and the
      permutation-based p-value of this MAX gTDT. All these methods are applied to
      whole-genome scans of the case-parent trios from the International Cleft
      Consortium. These applications show our procedures dramatically reduce the
      required computing time compared to the conventional iterative methods allowing,
      for example, the analysis of hundreds of thousands of SNPs in a few minutes
      instead of several hours.

PMID- 22150645
TI  - Pure haploinsufficiency for Dravet syndrome Na(V)1.1 (SCN1A) sodium channel
      truncating mutations.
AB  - PURPOSE: Dravet syndrome (DS), a devastating epileptic encephalopathy, is mostly
      caused by mutations of the SCN1A gene, coding for the voltage-gated Na(+) channel
      Na(V)1.1 alpha subunit. About 50% of SCN1A DS mutations truncate Na(V)1.1,
      possibly causing complete loss of its function. However, it has not been
      investigated yet if Na(V)1.1 truncated mutants are dominant negative, if they
      impair expression or function of wild-type channels, as it has been shown for
      truncated mutants of other proteins (e.g., Ca(V) channels). We studied the effect
      of two DS truncated Na(V)1.1 mutants, R222* and R1234*, on coexpressed wild-type
      Na(+) channels. METHODS: We engineered R222* or R1234* in the human cDNA of
      Na(V)1.1 (hNa(V)1.1) and studied their effect on coexpressed wild-type hNa(V)1.1,
      hNa(V)1.2 or hNa(V)1.3 cotransfecting tsA-201 cells, and on hNa(V)1.6
      transfecting an human embryonic kidney (HEK) cell line stably expressing this
      channel. We also studied hippocampal neurons dissociated from Na(V)1.1 knockout
      (KO) mice, an animal model of DS expressing a truncated Na(V)1.1 channel. KEY
      FINDINGS: We found no modifications of current amplitude coexpressing the
      truncated mutants with hNa(V)1.1, hNa(V)1.2, or hNa(V)1.3, but a 30% reduction
      coexpressing them with hNa(V)1.6. However, we showed that also coexpression of
      functional full-length hNa(V)1.1 caused a similar reduction. Therefore, this
      effect should not be involved in the pathomechanism of DS. Some gating properties
      of hNa(V)1.1, hNa(V)1.3, and hNa(V)1.6 were modified, but recordings of
      hippocampal neurons dissociated from Na(V)1.1 KO mice did not show any
      significant modifications of these properties. Therefore, Na(V)1.1 truncated
      mutants are not dominant negative, consistent with haploinsufficiency as the
      cause of DS. SIGNIFICANCE: We have better clarified the pathomechanism of DS,
      pointed out an important difference between pathogenic truncated Ca(V)2.1 mutants
      and hNa(V)1.1 ones, and shown that hNa(V)1.6 expression can be reduced in
      physiologic conditions by coexpression of hNa(V)1.1. Moreover, our data may
      provide useful information for the development of therapeutic approaches.

PMID- 22150646
TI  - Will direct laryngoscopy become an extinct skill?

PMID- 22150647
TI  - A policy impact analysis of the mandatory NCAA sickle cell trait screening
      program.
AB  - OBJECTIVE: To estimate the impact of the mandatory National Collegiate Athletic
      Association (NCAA) sickle cell trait (SCT) screening policy on the identification
      of sickle cell carriers and prevention of sudden death. DATA SOURCE: We used NCAA
      reports, population-based SCT prevalence estimates, and published risks for
      exercise-related sudden death attributable to SCT. STUDY DESIGN: We estimated the
      number of sickle cell carriers identified and the number of potentially
      preventable sudden deaths with mandatory SCT screening of NCAA Division I
      athletes. We calculated the number of student-athletes with SCT using a
      conditional probability based upon SCT prevalence data and self-identified
      race/ethnicity status. We estimated sudden deaths over 10 years based on
      published attributable risk of exercise-related sudden death due to SCT.
      PRINCIPAL FINDINGS: We estimate that over 2,000 NCAA Division I student-athletes
      with SCT will be identified under this screening policy and that, without
      intervention, about seven NCAA Division I student-athletes would die suddenly as
      a complication of SCT over a 10-year period. CONCLUSION: Universal sickle cell
      screening of NCAA Division I student-athletes will identify a substantial number
      of sickle cell carriers. A successful intervention could prevent about seven
      deaths over a decade.

PMID- 22150648
TI  - Case report: bilateral PAES as cause of lower leg pain in young athlete.

PMID- 22150649
TI  - Is childhood sexual abuse related to self-injurious behavior?

PMID- 22150651
TI  - Prolotherapy for chronic musculoskeletal pain.

PMID- 22150652
TI  - EHR implementation without meaningful use can lead to worse outcomes.
AB  - Defying expectations, typical electronic health record (EHR) use in practices
      belonging to a primary care network has been associated with poorer diabetes care
      quality and outcomes. Current expansion of primary care EHR implementation must
      focus on use that improves care.

PMID- 22150653
TI  - What my cancer taught me: quit smoking before it's too late.

PMID- 22150654
TI  - Effect of mammography on breast cancer mortality.

PMID- 22150655
TI  - Management of constipation in patients receiving palliative care.

PMID- 22150656
TI  - Treatment and prevention of kidney stones: an update.
AB  - The incidence of nephrolithiasis (kidney stones) is rising worldwide, especially
      in women and with increasing age. Kidney stones are associated with chronic
      kidney disease. Preventing recurrence is largely specific to the type of stone
      (e.g., calcium oxalate, calcium phosphate, cystine, struvite [magnesium ammonium
      phosphate]), and uric acid stones); however, even when the stone cannot be
      retrieved, urine pH and 24-hour urine assessment provide information about stone
      forming factors that can guide prevention. Medications, such as protease
      inhibitors, antibiotics, and some diuretics, increase the risk of some types of
      kidney stones, and patients should be counseled about the risks of using these
      medications. Managing diet, medication use, and nutrient intake can help prevent
      the formation of kidney stones. Obesity increases the risk of kidney stones.
      However, weight loss could undermine prevention of kidney stones if associated
      with a high animal protein intake, laxative abuse, rapid loss of lean tissue, or
      poor hydration. For prevention of calcium oxalate, cystine, and uric acid stones,
      urine should be alkalinized by eating a diet high in fruits and vegetables,
      taking supplemental or prescription citrate, or drinking alkaline mineral waters.
      For prevention of calcium phosphate and struvite stones, urine should be
      acidified; cranberry juice or betaine can lower urine pH. Antispasmodic
      medications, ureteroscopy, and metabolic testing are increasingly being used to
      augment fluid and pain medications in the acute management of kidney stones.

PMID- 22150657
TI  - Preventing kidney stones with diet and nutrition.

PMID- 22150658
TI  - Diagnosis and management of rheumatoid arthritis.
AB  - Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory
      arthritis. Women, smokers, and those with a family history of the disease are
      most often affected. Criteria for diagnosis include having at least one joint
      with definite swelling that is not explained by another disease. The likelihood
      of a rheumatoid arthritis diagnosis increases with the number of small joints
      involved. In a patient with inflammatory arthritis, the presence of a rheumatoid
      factor or anti-citrullinated protein antibody, or elevated C-reactive protein
      level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid
      arthritis. Initial laboratory evaluation should also include complete blood count
      with differential and assessment of renal and hepatic function. Patients taking
      biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis.
      Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with
      disease-modifying antirheumatic agents. Combinations of medications are often
      used to control the disease. Methotrexate is typically the first-line drug for
      rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors,
      are generally considered second-line agents or can be added for dual therapy. The
      goals of treatment include minimization of joint pain and swelling, prevention of
      radiographic damage and visible deformity, and continuation of work and personal
      activities. Joint replacement is indicated for patients with severe joint damage
      whose symptoms are poorly controlled by medical management.

PMID- 22150659
TI  - Personality disorders: review and clinical application in daily practice.
AB  - Personality disorders have been documented in approximately 9 percent of the
      general U.S. population. Psychotherapy, pharmacotherapy, and brief interventions
      designed for use by family physicians can improve the health of patients with
      these disorders. Personality disorders are classified into clusters A, B, and C.
      Cluster A includes schizoid, schizotypal, and paranoid personality disorders.
      Cluster B includes borderline, histrionic, antisocial, and narcissistic
      personality disorders. Cluster C disorders are more prevalent and include
      avoidant, dependent, and obsessive-compulsive personality disorders. Many
      patients with personality disorders can be treated by family physicians. Patients
      with borderline personality disorder may benefit from the use of omega-3 fatty
      acids, second-generation antipsychotics, and mood stabilizers. Patients with
      antisocial personality disorder may benefit from the use of mood stabilizers,
      antipsychotics, and antidepressants. Other therapeutic interventions include
      motivational interviewing and solution-based problem solving.

PMID- 22150660
TI  - Management of falls in older persons: a prescription for prevention.
AB  - Although falls are a common cause of injury in older persons, they are not just a
      normal part of the aging process. The American Geriatrics Society and British
      Geriatrics Society recommend that all adults older than 65 years be screened
      annually for a history of falls or balance impairment. An individualized risk
      assessment should be performed, with corresponding multifactorial intervention,
      for those who report a single fall and have unsteadiness; who report two or more
      falls; who report difficulties with gait or balance; or who seek medical
      attention because of a fall. The following components should be included in
      multifactorial interventions: exercise, particularly balance, strength, and gait
      training; modification of the home environment; minimization of medications,
      especially psychoactive medications; management of postural hypotension; and
      management of foot problems and footwear. These interventions are effective in
      decreasing falls and fall-related injuries in the community and nursing home
      settings, as well as in decreasing the number of persons who fall in the subacute
      hospital setting. Prevention of falls and, most importantly, of injury and death
      is possible. An evidence-based fall prevention prescription may be used to
      efficiently accomplish management.

PMID- 22150661
TI  - Tips for preventing falls.

PMID- 22150662
TI  - Large, dark lesion on the arm present since birth.

PMID- 22150663
TI  - FPIN's clinical inquiries. Treatment of nongenital warts.

PMID- 22150665
TI  - Callosal thickness reductions relate to facial dysmorphology in fetal alcohol
      spectrum disorders.
AB  - BACKGROUND: Structural abnormalities of the corpus callosum (CC), such as reduced
      size and increased shape variability, have been documented in individuals with
      fetal alcohol spectrum disorders (FASD). However, the regional specificity of
      altered CC structure, which may point to the timing of neurodevelopmental
      disturbances and/or relate to specific functional impairments, remains unclear.
      Furthermore, associations between facial dysmorphology and callosal structure
      remain undetermined. METHODS: One hundred and fifty-three participants (age range
      8 to 16) including 82 subjects with FASD and 71 nonexposed controls were included
      in this study. The structural magnetic resonance imaging data of these subjects
      was collected at 3 sites (Los Angeles and San Diego, California, and Cape Town,
      South Africa) and analyzed using classical parcellation schemes, as well as more
      refined surface-based geometrical modeling methods, to identify callosal
      morphological alterations in FASD at high spatial resolution. RESULTS: Reductions
      in callosal thickness and area, specifically in the anterior third and the
      splenium, were observed in FASD compared with nonexposed controls. In addition,
      reduced CC thickness and area significantly correlated with reduced palpebral
      fissure length. CONCLUSIONS: Consistent with previous reports, findings suggest
      an adverse effect of prenatal alcohol exposure on callosal growth and further
      indicate that fiber pathways connecting frontal and parieto-occipital regions in
      each hemisphere may be particularly affected. Significant associations between
      callosal and facial dysmorphology provide evidence for a concurrent insult to
      midline facial and brain structural development in FASD.

PMID- 22150667
TI  - Night eating syndrome: an overview.
AB  - OBJECTIVES: The purpose of this review is to outline the nosographic
      characteristics of NES and the most reliable ethiopathogenetic theories in
      relation to the most recent evidence in the literature. KEY FINDINGS: The night
      eating syndrome (NES) is a disorder occurring at the stated time, that does not
      meet the criteria for any specific eating disorder. NES is characterized by a
      reduced feeding during the day, evening hyperphagia accompanied by frequent
      nocturnal awakenings associated with conscious episodes of compulsive ingestion
      of food and abnormal circadian rhythms of food and other neuroendocrine factors.
      Frequently it is associated with obesity and depressed mood. We highlight the
      therapeutic possibilities of some drugs, especially selective serotonin re-uptake
      inhibitors (SSRIs), which reduce the hyperactivity of the serotonin transporter
      in NES and significantly improve the clinical picture of this disease.
      CONCLUSIONS: Night eating syndrome is of importance clinically because of its
      association with obesity. The recognition and effective treatment of NES may be
      an increasingly important way to treat a subset of the obese population.
      Treatment of the syndrome, however, is still in its infancy. One clinical trial
      has reported efficacy with the SSRI sertraline. Other treatments, such as the
      anticonvulsant topiramate, phototherapy, and other SSRIs, may also offer future
      promise. Particularly useful would be studies involving brain scans (magnetic
      resonance imaging or single-photon emission computed tomography) of patients with
      NES compared with the healthy population, to investigate more thoroughly the
      possible alterations involved in the pathogenesis of NES.

PMID- 22150668
TI  - Microneedles: an emerging transdermal drug delivery system.
AB  - OBJECTIVES: One of the thrust areas in drug delivery research is transdermal drug
      delivery systems (TDDS) due to their characteristic advantages over oral and
      parenteral drug delivery systems. Researchers have focused their attention on the
      use of microneedles to overcome the barrier of the stratum corneum. Microneedles
      deliver the drug into the epidermis without disruption of nerve endings. Recent
      advances in the development of microneedles are discussed in this review for the
      benefit of young scientists and to promote research in the area. KEY FINDINGS:
      Microneedles are fabricated using a microelectromechanical system employing
      silicon, metals, polymers or polysaccharides. Solid coated microneedles can be
      used to pierce the superficial skin layer followed by delivery of the drug.
      Advances in microneedle research led to development of dissolvable/degradable and
      hollow microneedles to deliver drugs at a higher dose and to engineer drug
      release. Iontophoresis, sonophoresis and electrophoresis can be used to modify
      drug delivery when used in concern with hollow microneedles. Microneedles can be
      used to deliver macromolecules such as insulin, growth hormones,
      immunobiologicals, proteins and peptides. Microneedles containing
      'cosmeceuticals' are currently available to treat acne, pigmentation, scars and
      wrinkles, as well as for skin tone improvement. SUMMARY: Literature survey and
      patents filled revealed that microneedle-based drug delivery system can be
      explored as a potential tool for the delivery of a variety of macromolecules that
      are not effectively delivered by conventional transdermal techniques.

PMID- 22150669
TI  - The influence of AT1002 on the nasal absorption of molecular weight markers and
      therapeutic agents when co-administered with bioadhesive polymers and an AT1002
      antagonist, AT1001.
AB  - OBJECTIVES: The purpose of this study was to demonstrate the effects of the tight
      junction permeation enhancer, AT1002, on the nasal absorption of molecular weight
      markers and low bioavailable therapeutic agents co-administered with bioadhesive
      polymers or zonulin antagonist. METHODS: The bioadhesive polymers, carrageenan
      and Na-CMC, were prepared with AT1002 to examine the permeation-enhancing effect
      of AT1002 on the nasal absorption of inulin, calcitonin and saquinavir after
      nasal administration to Sprague-Dawley rats. Blood samples were collected over a
      6-hour period from a jugular cannula. In addition, we determined whether AT1002
      exerts a permeation-enhancing effect via activation of PAR-2 specific binding to
      a putative receptor of zonulin. To examine this zonulin antagonist, AT1001, was
      administered 30 min prior to dosing with an AT1002/inulin solution and blood
      samples were collected over a 6-hour period. KEY FINDINGS: The bioadhesive
      polymers did not directly increase the absorption of inulin, calcitonin and
      saquinavir, but promoted the permeation-enhancing effect of AT1002 when delivered
      nasally, thereby significantly increasing the absorption of each drug. Pre
      treatment with AT1001 antagonized the zonulin receptor and significantly
      minimized the permeation-enhancing effect of AT1002. CONCLUSION: These findings
      will assist in understanding the permeation-enhancing capability of and the
      receptor binding of AT1002. Further, combining AT1002 with carrageenan supports
      the development of the mucosal delivery of therapeutic agents that have low
      bioavailability even with bioadhesive agents.

PMID- 22150670
TI  - A case study exploring the impact of an oxygen barrier coating on formulation
      stability, in-vitro dissolution and bioperformance.
AB  - OBJECTIVES: The impact of a carmellose sodium (sodium carboxymethycellulose)
      based coat (Opaglos 2) on the stability of an oxygen-sensitive compound A and in
      vitro dissolution and bioperformance of compound B has been investigated.
      METHODS: Tablets containing compounds A and B were coated with various weight
      gains of Opaglos 2 and a comparative elegance coating (poly(vinyl alcohol)-based
      Opadry II). Film-coated tablets were assessed for oxidative degradation under
      accelerated stability conditions (30 degrees C/65% RH and 40 degrees C/75% RH).
      KEY FINDINGS: An apparent rank order of restriction of oxygen (O(2) )
      permeability afforded by the coatings was observed, with only higher Opaglos 2
      coating weight gains (6 and 8% w/w) providing adequate oxidative degradation
      stability for up to 52 weeks. Improved stability at the higher coating weight
      gains was attributed to incomplete polymeric film formation at lower coating
      weight gains. The 6% and 8% w/w Opaglos 2 formulations showed dissolution
      retardation compared with elegance-coated formulations in USP dissolution
      apparatus II, predicting significant impact on formulation bioperformance.
      However, pharmacokinetic studies in Beagle dogs showed similar bioperformance for
      all formulations. CONCLUSIONS: The Opaglos 2 coating system evaluated in these
      studies afforded adequate protection from oxidative degradation with no negative
      impact on bioperformance as compared to elegance coating. However, further
      studies are needed using several compounds to assess the broader applicability of
      these coatings.

PMID- 22150671
TI  - Parametric simulation of drug release from hydrogel-based matrices.
AB  - OBJECTIVES: In this work a model recently proposed to describe the drug release
      from hydrogel-based matrices was applied to describe the fractional drug release
      from matrices based on hydroxypropylmethylcellulose (HPMC) and diclofenac.
      METHODS: The model, firstly proposed to describe the behaviour of systems based
      on HPMC and theophylline and a single set of preparation variables, is based on
      mass balances and transport phenomena evaluation and it was solved by an FEM
      based numerical code. The experimental data on the HPMC-diclofenac matrices,
      taken from literature, have been obtained by varying the drug loading ratio, the
      compression force, the powder size of both the drug and the polymer. KEY
      FINDINGS: A good agreement between experimental data and model predictions, as
      calculated in the present work, was obtained without the use of any adjustable
      parameters. CONCLUSIONS: The predictive nature of the model has been confirmed,
      even changing the drug molecule and other preparative parameters.

PMID- 22150672
TI  - Transport mechanisms of flavanone aglycones across Caco-2 cell monolayers and
      artificial PAMPA membranes.
AB  - OBJECTIVES: We recently reported that flavanone aglycones (hesperetin, naringenin
      and eriodictyol) are efficiently absorbed via proton-coupled active transport, in
      addition to transcellular passive diffusion, in Caco-2 cells. Here, we aimed to
      evaluate in detail the absorption mechanisms of these flavanones, as well as
      homoeriodictyol and sakuranetin. METHODS: We evaluated the absorption mechanisms
      of the above compounds by means of in vitro studies in Caco-2 cells in parallel
      with an artificial membrane permeation assay (PAMPA) under pH-gradient and iso-pH
      conditions. KEY FINDINGS: Comparison of the permeability characteristics of
      flavanones in Caco-2 cells and in PAMPA under these conditions, as well as a
      consideration of the physicochemical properties, indicated that hesperetin,
      naringenin, eriodictyol and homoeriodictyol were efficiently transported by
      passive diffusion according to the pH-partition hypothesis, except in the case of
      sakuranetin. However, transport of all flavanones were remarkably temperature
      dependent, and was significantly reduced when Caco-2 cells were treated with
      amino acid-modifying reagents. CONCLUSIONS: Our data confirm that both passive
      diffusion and an active transport mechanism contribute to flavanone absorption
      through human intestinal epithelium.

PMID- 22150673
TI  - Cellular delivery of PEGylated PLGA nanoparticles.
AB  - OBJECTIVES: The objective of this study was to investigate the efficiency of
      uptake of PEGylated polylactide-co-gycolide (PLGA) nanoparticles by breast cancer
      cells. METHODS: Nanoparticles of PLGA containing various amounts of polyethylene
      glycol (PEG, 5%-15%) were prepared using a double emulsion solvent evaporation
      method. The nanoparticles were loaded with coumarin-6 (C6) as a fluorescence
      marker. The particles were characterized for surface morphology, particle size,
      zeta potential, and for cellular uptake by 4T1 murine breast cancer cells. KEY
      FINDINGS: Irrespective of the amount of PEG, all formulations yielded smooth
      spherical particles. However, a comparison of the particle size of various
      formulations showed bimodal distribution of particles. Each formulation was later
      passed through a 1.2 um filter to obtain target size particles (114-335 nm) with
      zeta potentials ranging from -2.8 mV to -26.2 mV. While PLGA-PEG di-block (15%
      PEG) formulation showed significantly higher 4T1 cellular uptake than all other
      formulations, there was no statistical difference in cellular uptake among PLGA,
      PLGA-PEG-PLGA tri-block (10% PEG), PLGA-PEG di-block (5% PEG) and PLGA-PEG di
      block (10% PEG) nanoparticles. CONCLUSION: These preliminary findings indicated
      that the nanoparticle formulation prepared with 15% PEGylated PLGA showed maximum
      cellular uptake due to it having the smallest particle size and lowest zeta
      potential.

PMID- 22150674
TI  - Ethanol consumption increases the expression of endothelial nitric oxide
      synthase, inducible nitric oxide synthase and metalloproteinases in the rat
      kidney.
AB  - OBJECTIVES: The effects of longterm ethanol consumption on the levels of nitric
      oxide (NO) and the expression of endothelial NO synthase (eNOS), inducible NO
      synthase (iNOS) and metalloproteinase-2 (MMP-2) were studied in rat kidney.
      METHODS: Male Wistar rats were treated with 20% ethanol (v/v) for 6 weeks.
      Nitrite and nitrate generation was measured by chemiluminescence. Protein and
      mRNA levels of eNOS and iNOS were assessed by immunohistochemistry and
      quantitative real-time polymerase chain reaction, respectively. MMP-2 activity
      was determined by gelatin zymography. Histopathological changes in kidneys and
      indices of renal function (creatinine and urea) and tissue injury (mitochondrial
      respiration) were also investigated. RESULTS: Chronic ethanol consumption did not
      alter malondialdehyde levels in the kidney. Ethanol consumption induced a
      significant increase in renal nitrite and nitrate levels. Treatment with ethanol
      increased mRNA expression of both eNOS and iNOS. Immunohistochemical assays
      showed increased immunostaining for eNOS and iNOS after treatment with ethanol.
      Kidneys from ethanol-treated rats showed increased activity of MMP-2.
      Histopathological investigation of kidneys from ethanol-treated animals revealed
      tubular necrosis. Indices of renal function and tissue injury were not altered in
      ethanol-treated rats. CONCLUSIONS: Ethanol consumption increased renal
      metalloproteinase expression/activity, which was accompanied by histopathological
      changes in the kidney and elevated NO generation. Since iNOS-derived NO and MMPs
      contribute to progressive renal injury, the increased levels of NO and MMPs
      observed in ethanol-treated rats might contribute to progressive renal damage.

PMID- 22150675
TI  - Mechanisms of aggregation inhibition by aspirin and nitrate-aspirin prodrugs in
      human platelets.
AB  - OBJECTIVES: Aspirin is the mainstay of anti-platelet therapy in the secondary
      prevention of cardiovascular disease. However, problems with aspirin safety and
      resistance demand clinical strategies based on multiple pharmacological
      approaches. Prodrugs of aspirin may offer beneficial effects in terms of gastro
      intestinal safety and multiple pharmacological approaches. However, the
      pharmacological profile of aspirin prodrugs in human platelets has not been
      completed yet. We aimed to compare the effects of aspirin and prodrugs of aspirin
      (1-5) on human platelet aggregation stimulated by ADP and collagen and associated
      receptor expression (GPIIb/IIIa and P-selectin) in platelet-rich plasma (PRP) and
      washed platelets (WP). METHODS: As aspirin is released from prodrugs following
      esterase hydrolysis we studied the expression and activity of
      butyrylcholineterase (BuChE) and carboxyesterase (CE) in plasma and platelets.
      The mechanism of prodrug-induced platelet aggregation inhibition was explored by
      studying the effects of plasma and purified human BuChE on aggregation. Finally,
      the relative contribution of nitric oxide (NO) bioactivity to nitrate-containing
      prodrugs of aspirin-induced inhibition of aggregation was determined using 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ,) a selective inhibitor of the
      soluble guanylyl cyclase. KEY FINDINGS: ST0702, 2, a nicotinic acid-aspirin
      codrug was equipotent with aspirin with respect to inhibition of collagen-induced
      platelet aggregation. Compound 4, a NO releasing aspirin was the most potent
      inhibitor of ADP-induced platelet aggregation, an effect partially reversed by
      ODQ. The platelet inhibitory effects of aspirin prodrugs were time-dependent as
      the maximal inhibitory effects against collagen-induced aggregation were achieved
      by aspirin at 2 min, 1 at 5 min and ST0702 at 15 min. The aspirin prodrugs were
      significantly less potent in WP than in PRP and the reverse was true of aspirin.
      In the presence of complete BuChE inhibition in PRP, there was almost complete
      loss of aspirin prodrug, but not aspirin anti-aggregatory activity.
      Interestingly, CE activity was observed in WP and platelet lysate with pNPA
      substrate. Accordingly, 1 and ST0702 retained 50% and 100% anti-aggregatory
      activity at maximal concentrations in WP, which was attenuated in the presence of
      esterase inhibitor phenylmethylsulphonyl fluoride. CONCLUSIONS: The inhibitory
      effect of aspirin prodrugs in PRP is due to prodrug activation by BuChE. In
      contrast, the platelet-inhibitory effects of aspirin prodrugs in WP may be
      mediated through the activity of platelet CE. Compound 4, a NO-containing aspirin
      prodrug, may exert dual inhibitory effects in platelets. Thus, aspirin prodrugs
      effectively inhibit human platelet aggregation and as such may be an alternative
      to conventional aspirin.

PMID- 22150676
TI  - 3'-O, 4'-O-aromatic acyl substituted 7,8-pyranocoumarins: a new class of P
      glycoprotein modulators.
AB  - OBJECTIVES: P-glycoprotein (Pgp) overexpression in tumour cells leads to
      multidrug resistance (MDR) and causes failure in cancer chemotherapy. We have
      previously identified (+/-)-praeruptorin A (PA) as a potential lead compound for
      Pgp modulators. In this study we investigated the MDR-reversing activities of PA
      derivatives. METHODS: Series 7,8-pyranocoumarins with various C-3' and C-4' side
      chains had been semi-synthesized and their MDR-reversing activity was
      investigated in Pgp-overexpressing MDR tumour cell line HepG2/Dox and in a KB V1
      xenograft animal model. KEY FINDINGS: All 7,8-pyranocoumarins exhibited equal or
      higher activity in modulating Pgp. DCK (12), DMDCK (15), 16, 21, 23 and 24 at 4
      um achieved 91%~99% decrease in IC50 value (concentration inhibiting cell growth
      by 50%) of anticancer agents vinblastine, doxorubicin, puromycin and paclitaxel,
      and were more active than others. DMDCK also remarkably enhanced the growth
      inhibitory effect of paclitaxel on KB V1 xenografts (P < 0.05), showing a potency
      required for clinical usage. Mechanistic studies suggested that these 7,8
      pyranocoumarins might reverse Pgp-MDR through directly binding to substrate
      binding site(s) or allosteric site(s) on Pgp therefore impairing Pgp-mediated
      drug transport. CONCLUSIONS: Results from the study suggested that 3'-O, 4'-O
      aromatic acyl substituted 7,8-pyranocoumarins could serve as a new class of Pgp
      modulator. Acyls play an important role in maintaining and enhancing the Pgp
      modulating ability of pyranocoumarins. 3,4-Dimethoxyl substituted aromatic acyls,
      bearing a methoxy that might interact with Pgp as hydrogen bond accepter, were
      shown to be the most potent for reversing MDR.

PMID- 22150677
TI  - Alteronol inhibits proliferation in HeLa cells through inducing a G1-phase
      arrest.
AB  - OBJECTIVES: Alteronol is a novel compound purified from fermentation products of
      a microorganism in the bark of the yew tree. The study was designed to evaluate
      the anticancer effects of alteronol. METHODS: Human cervical carcinoma cell line
      HeLa was cultured in vitro. The cell viability was evaluated by using
      sulforhodamine B assay. The cell cycle distribution was analysed by flow
      cytometry. The level of cyclin D1 protein was evaluated using Western blot
      analysis. The changes in cyclinD1, CDK4 and p21 were detected by ELISA assay and
      the changes in G1-related regulators were detected by RT-PCR assay. KEY FINDINGS:
      Our data showed that alteronol inhibited the proliferation of HeLa cells and
      induced G1 phase arrest. Downregulation of the mRNA levels of CDK2, CDK4 and
      cyclin D1 and upregulation of p21 in alteronol-treated cells were observed.
      CONCLUSIONS: Downregulation of the mRNA levels of CDK2, CDK4 and cyclin D1 and
      upregulation of p21 might be a possible mechanism for the inhibition of
      proliferation induced by alteronol in HeLa cells.

PMID- 22150678
TI  - Nicotine and vascular endothelial dysfunction in female ovariectomized rats: role
      of estrogen replacement therapy.
AB  - OBJECTIVES: The protective effects of estrogen replacement therapy (ERT) against
      oxidative injury and endothelial dysfunction in the aortic tissues induced with
      nicotine in ovariectomized (OVX) rats were investigated. METHODS: Female rats
      were divided into a sham-operated group (n = 8) and four groups in which OVX rats
      received either vehicle (0.1 ml sesame oil, i.m., n = 8), or nicotine (0.1 mg/kg,
      s.c., n = 8), or estradiol benzoate (0.1 mg/kg, i.m., n = 8), or both nicotine
      and estradiol benzoate (n = 8) starting at week 5 after the surgery and
      continuing for the following 6 weeks. KEY FINDINGS: ERT was effective in
      preventing the rise in plasma lipid profile, atherogenic index and the level of
      induced endothelin-1 (ET-1) in nicotine-treated OVX rats. It also reduced aortic
      malondialdehyde, hydroxyproline levels, calcium content and caspase-3 expression
      induced in nicotine-treated OVX rats. ERT increased serum estradiol, high-density
      lipoprotein cholesterol and nitric oxide levels in nicotine-treated OVX rats.
      Furthermore, ERT was effective in restoring reduced glutathione and cyclic
      guanosine monophosphate contents and endothelial nitric oxide synthase expression
      in aortic tissues of nicotine-treated OVX rats. CONCLUSIONS: Short-term ERT could
      be a promising therapeutic strategy to minimize nicotine-induced oxidative stress
      and vascular endothelial dysfunction in menopausal women subjected to
      environmental smoke.

PMID- 22150679
TI  - Dexmedetomidine protects against oxygen-glucose deprivation-induced injury
      through the I2 imidazoline receptor-PI3K/AKT pathway in rat C6 glioma cells.
AB  - OBJECTIVES: To explore the protection and the mechanism of dexmedetomidine on the
      oxygen-glucose deprivation (OGD) insults in rat C6 glioma cells. METHODS: Cells
      were subjected to OGD then assessed by viability studies. After dexmedetomidine
      treatment, p-AKT, hypoxia-inducible factor (HIF)-1alpha, vascular endothelial
      growth factor (VEGF) and RTP801 expression were measured. KEY FINDINGS: Three
      hours of OGD decreased cell viability to 48.8%, which was reversed to 67.4% by 1
      um dexmedetomidine. Hoechst 33342 and propidium iodide double stains showed that
      the protection of dexmedetomidine was mainly by an anti-apoptosis effect, which
      was also strengthened by decreasing caspase-3 expression. Dexmedetomidine
      protection was mainly blocked by the I2 imidazoline receptor antagonist idazoxan
      and BU 224, but not by the alpha(1)-adrenoceptor antagonist prazosin, the
      alpha(2)-adrenoceptor antagonist yohimbine and RX 821002, or the I1 imidazoline
      receptor antagonist efaroxan. On the other hand, dexmedetomidine enhanced AKT
      phosphorylation. Furthermore, the protection of dexmedetomidine was blocked by
      the PI3K/AKT inhibitor wortmannin. The proteins of HIF-1alpha, VEGF and RTP801
      were significantly increased by dexmedetomidine treatment. CONCLUSIONS:
      Dexmedetomidine activated the I2 imidazoline receptor-PI3K/AKT pathway, and up
      regulated HIF-1alpha, VEGF and RTP801 expression to protect against OGD-induced
      injury in rat C6 cells.

PMID- 22150680
TI  - Susceptibility of glucocorticoids to colonic metabolism and pharmacologic
      intervention in the metabolism: implication for therapeutic activity of colon
      specific glucocorticoid 21-sulfate sodium at the target site.
AB  - OBJECTIVES: The systemic side effects of glucocorticoids have prevented their
      long-term use for treatment of inflammatory bowel disease. Colon-specific
      delivery of glucocorticoids has been adopted as a strategy to circumvent the
      toxicological trouble. Glucocorticoids delivered to the large intestine might
      undergo metabolisms by colonic microflora, which should affect therapeutic
      availability at the target site. It was investigated whether the susceptibility
      of glucocorticoids to the colonic metabolisms and pharmacologic intervention in
      the metabolism could modulate the therapeutic availability of colon-targeted
      glucocorticoids. METHODS: Various glucocorticoids and their derivatives,
      glucocorticoid 21-sulfate sodium compounds, were incubated in the cecal contents
      in the presence or absence of reduction inhibitors and the change in the levels
      of the drugs was monitored. KEY FINDINGS: The accumulation profiles of the
      corresponding glucocorticoids liberated from glucocorticoid 21-sulfate sodium
      compounds vary, depending on the metabolic susceptibility of glucocorticoids.
      Reduction inhibitors prevented the cecal metabolisms of glucocorticoids, which
      was most prominent for prednisolone (PD) and methylprednisolone (MP). Moreover,
      reduction inhibitors increased the accumulated amount of MP and PD released from
      PD- and MP-21-sulfate sodium in the cecal contents. CONCLUSIONS: Our data provide
      information useful for selection of a glucocorticoid and a pharmacologic strategy
      for the design of an efficient colon-specific glucocorticoid prodrug.

PMID- 22150681
TI  - Effects and mechanisms of total Panax notoginseng saponins on proliferation of
      vascular smooth muscle cells with plasma pharmacology method.
AB  - OBJECTIVES: Total Panax notoginseng saponin (TPNS) is extracted from Panax
      notoginseng. Our previous studies suggested that TPNS could inhibit intimal
      hyperplasia. This study discussed the impact of TPNS on the proliferation of
      vascular smooth muscle cells (VSMCs) and revealed the associated mechanisms
      through cell cycle-related factors and extracellular regulated protein kinase
      (ERK) signal transduction pathway. METHODS: A VSMC proliferation model induced by
      platelet-derived growth factor (PDGF) was established to observe the effects of
      rat drug-containing plasma on VSMC proliferation. KEY FINDINGS: After being
      stimulated by PDGF, the proliferating cell nuclear antigen (PCNA) and c-fos
      content increased, while up-regulation of cyclinD1, cyclin-dependent kinase-4
      (CDK4) and down-regulation of p21 protein were observed. These changes were
      inhibited by atorvastatin and TSPN drug-containing plasma, and the inhibitive
      activity in both groups was not significant. Furthermore, both atorvastatin and
      TSPN could obviously inhibit the activation of PDGF-induced P-ERK1/2 and increase
      the content of MKP-1, there were also no significant differences. CONCLUSIONS:
      These results suggested that atorvastatin and TPNS could inhibit VSMC
      proliferation by inhibiting the activation of ERK signalling pathway.

PMID- 22150682
TI  - beta-Elemene induces apoptosis as well as protective autophagy in human non-small
      cell lung cancer A549 cells.
AB  - OBJECTIVES: beta-Elemene, a novel traditional Chinese medicine, has been shown to
      be effective against a wide range of tumours. In this study, the antitumour
      effect of beta-elemene on human non-small-cell lung cancer (NSCLC) A549 cells and
      the mechanism involved have been investigated. METHODS: Cell viability and
      apoptosis were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein
      expression was assayed by Western blotting. Autophagy was evaluated under
      fluorescence microscopy and transmission electron microscopy. KEY FINDINGS: beta
      Elemene inhibited the viability of A549 cells in a dose-dependent manner. This
      suppression of cell viability was due to the induction of apoptosis. Further
      study showed that beta-elemene inhibited the activity of the
      PI3K/Akt/mTOR/p70S6K1 signalling pathway, and at the same time it triggered a
      robust autophagy. The autophagy was characterized by the accumulation of punctate
      LC3 dots in the cytoplasm, morphological changes, and the increased levels of LC3
      II as well as Atg5-Atg12 conjugated proteins. Inhibition of autophagy with
      chlorochine significantly enhanced the antitumour effect of beta-elemene.
      CONCLUSIONS: Our data indicated that beta-elemene inhibited the activity of the
      PI3K/Akt/mTOR/p70S6K1 signalling pathway in human NSCLC A549 cells, which
      resulted in apoptosis as well as protective autophagy. A combination of beta
      elemene with autophagy inhibitor might be an effective therapeutic option for
      advanced NSCLC.

PMID- 22150683
TI  - The effect of propolis on CCL5 and IFN-gamma expression by peripheral blood
      mononuclear cells from leishmaniasis patients.
AB  - OBJECTIVES: Mucocutaneous leishmaniasis is associated with a strong Th1 immune
      response to Leishmania, which modulates chemokines and their receptors
      expression, affecting their migratory capacity. There are no antileishmanial
      vaccines available and chemotherapy still relies on the potentially toxic
      pentavalent antimonials. Propolis is a bee product with immunomodulatory and
      antiparasite activities, and researchers have been attracted to its potential for
      the development of new drugs. This work investigated the effects of propolis on
      CCL5 and IFN-gamma expression by peripheral blood mononuclear cells (PBMC) in
      order to evaluate a possible immunomodulatory action of propolis in patients with
      leishmaniasis compared to healthy control subjects. METHODS: PBMC were incubated
      in the absence or presence of propolis and the evaluation of a possible
      cytotoxicity of propolis was carried out using MTT assay. The expression level of
      CCL5 and IFN-gamma was determined by real-time PCR. KEY FINDINGS: Our data
      indicated that propolis modulates the immune response of leishmaniasis patients
      in vitro, affecting CCL5 and IFN-gamma expression by PBMC. CONCLUSIONS: Data
      suggested that propolis drives an anti-inflammatory response depending on
      concentration. Although propolis is a potential source of new and selective drugs
      for the treatment of leishmaniasis, its usefulness in the therapeutics should be
      further investigated.

PMID- 22150685
TI  - Evolution in a centralized transfusion service.
AB  - The metropolitan Seattle area has utilized a centralized transfusion service
      model throughout the modern era of blood banking. This approach has used four
      laboratories to serve over 20 hospitals and clinics, providing greater
      capabilities for all at a lower consumption of resources than if each depended on
      its own laboratory and staff for these functions. In addition, this centralized
      model has facilitated wider use of the medical capabilities of the blood center's
      physicians, and a county-wide network of transfusion safety officers is now being
      developed to increase the impact of the blood center's transfusion expertise at
      the patient's bedside. Medical expectations and traffic have led the blood center
      to evolve the centralized model to include on-site laboratories at facilities
      with complex transfusion requirements (e.g., a children's hospital) and to
      implement in all the others a system of remote allocation. This new capability
      places a refrigerator stocked with uncrossmatched units in the hospital but
      retains control over the dispensing of these through the blood center's computer
      system; the correct unit can be electronically cross-matched and released on
      demand, obviating the need for transportation to the hospital and thus speeding
      transfusion. This centralized transfusion model has withstood the test of time
      and continues to evolve to meet new situations and ensure optimal patient care.

PMID- 22150686
TI  - WBC reduction filtration efficacy performed at varying time intervals post
      collection.
AB  - BACKGROUND: A multisite blood center experienced unacceptable post-leukoreduction
      filtration white blood cell (WBC) counts at a few centers. Since prefiltration
      storage time and temperature were suspect, whole blood (WB) units were stored in
      transport shippers for at least 2 hours, cooling toward 1-6  degrees  C, before
      filtration. This study compared the effect of storage times in transport shippers
      on the residual WBC counts of leukoreduced units. STUDY DESIGN AND METHODS:
      Collection and filtration of WB units were accomplished with the use of the
      Fenwal Express System with Integral Sepacell RZ-2000 WB Leukocyte Reduction
      Filter. Units were collected and placed in transport shippers containing ice.
      Leukoreduction filtration was performed at designated intervals post-collection.
      Acceptable leukoreduction was defined as < 5 * 10(6) residual WBC. RESULTS: Fifty
      donor units were selected randomly over 3 months. Units were held in transport
      shippers, and WBC reduction was performed at designated post-collection
      intervals. Storage times ranged from 28 to 458 minutes. All residual WBC counts
      were acceptable. CONCLUSION: Storage time of WB units in transport shippers did
      not play a role in the efficacy of the leukoreduction. This study demonstrated
      the 2-hour storage time before leukoreduction filtration could be eliminated
      resulting in time savings and increased efficacy in the component production
      laboratory.

PMID- 22150687
TI  - Therapeutic phlebotomy procedures and their impact on a rural hospital's red
      blood cell inventory and fiscal stature.
AB  - BACKGROUND: Therapeutic phlebotomy (TP) programs offer an important community
      service and often provide financial and donor unit resources for the hospital.
      This study assessed the financial impact and red blood cell (RBC) inventory
      contribution of a small, rural hospital-based TP program. STUDY DESIGN AND
      METHODS: TP procedures over 13 months were evaluated at a 142-bed rural hospital.
      The hospital had a Food and Drug Administration variance for a hereditary
      hemochromatosis (HH) donor program. The revenue for the non-HH therapeutic
      phlebotomies and the savings attained for units added to RBC inventory from
      allogeneic eligible HH donors were compiled. RESULTS: During the study, 84
      patients were involved in the TP program. Of the 62 HH patients, 43 met
      eligibility requirements for allogeneic donations resulting in 207 donor units
      collected for the blood bank inventory and a savings of $21,000 in blood costs.
      Additionally, 22 non-HH patients underwent 183 TP procedures earning the hospital
      over $15,000 in net revenue. CONCLUSION: The TP program at this small, rural 142
      bed hospital provided a financial gain of $36,000 during the 13-month study
      period. The HH donor program contributed approximately 4% to the RBC inventory.
      The TP program at this small, rural 142-bed hospital proved to be financially
      lucrative and provided a community service to patients.

PMID- 22150688
TI  - Transfusion safety: is this the business of blood centers?
AB  - ATSO is in a unique position to break down organizational silos between hospitals
      and blood centers through the development of a collaborative relationship between
      the two entities. Use of the TSO as blood center staff centralizes the role into
      a consultative position thereby retaining the independence of the hospitals. The
      TSO position then becomes a value-added service offered by the blood center
      designed to supplement processes within the hospital.Whether the TSO is based in
      the hospital or the blood center, improvements are gained through appropriate
      utilization of blood components, reductions in hospital costs, ongoing education
      of hospital staff involved in transfusion practice, and increased availability of
      blood products within the community. Implementation and standardization of best
      practice processes for ordering and administration of blood products developed by
      TSOs leads to improved patient outcomes. As a liaison between hospitals and blood
      centers, the TSO integrates the mutual goal of transfusion safety: the provision
      of the safest blood product to the right patient at the right time for the right
      reason.

PMID- 22150689
TI  - Catching up with David Perez. Interview by Robert Carden.

PMID- 22150690
TI  - Intraocular lens implantation position sensitivity as a function of refractive
      error.
AB  - PURPOSE: To quantify the change in ocular aberrations due to intraocular lens
      (IOL) implantation position errors for pseudo-phakic eyes with different
      refractive errors. METHODS: The theoretical part of this work was based on ray
      tracing in emmetropic and myopic eye models. The possible misalignments i.e. the
      decentration, tilt and axial translation, of the IOLs were statistically combined
      together and analysed using Monte-Carlo simulations. Spherical IOLs with a 3 and
      5 mm pupil and an aspheric IOL with a 5 mm pupil were analysed as a function of
      refractive error. In the experimental part of the work, we built an IOL optical
      test bench including a model eye. The white light discrete point spread functions
      of misaligned IOLs were recorded by a CCD and we compared the change of the
      spread function as a result of misalignments for two spherical IOLs with
      different optical powers. RESULTS: The Monte-Carlo simulations showed that the
      average root-mean-square spot size at the retinal plane decreased with increasing
      myopic refractive error, i.e. lower power IOL. The experiments showed that a
      lower optical power spherical IOL had a less distributed point spread function
      than a higher optical power IOL, which supported the results of the simulation.
      CONCLUSION: Regarding IOLs designed for myopic patients, low power IOLs (for high
      myopes) were shown to be less sensitive to the misalignment than high power ones.
      Aspheric IOLs were more sensitive to position errors than spherical IOLs under
      the same conditions.

PMID- 22150691
TI  - The challenge of methicillin-resistant Staphylococcus aureus prevention in
      hemodialysis therapy.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infections have challenged
      care process and resource utilization in the acute hospital care setting for
      nearly 30 years. These infections have become important causes of morbidity,
      mortality, and a source of concern in the primary and emergency care context over
      the past decade. As individuals receiving recurrent therapy with features of both
      ambulatory care and acute care, hemodialysis patients are exposed to numerous
      opportunities for MRSA acquisition. Surprisingly, high prevalence rates for MRSA
      colonization have been demonstrated for both hemodialysis patients and their care
      providers. The necessity of vascular access and the persistent high prevalence of
      endovascular catheter use among patients repeatedly exposed to healthcare
      settings provide the perfect milieu for the troubling rates of MRSA infection,
      particularly bloodstream infections, in outpatient dialysis care. Dialysis
      industry shifts, including increased requirements for compliance and reporting in
      other areas of dialysis care, tax resources for infection prevention processes.
      Multifaceted strategies that include reassessment of vascular access care,
      attention to the interruption of MRSA transmission dynamics, and emphasis on
      organizational learning processes are needed to accomplish a meaningful reduction
      in the morbidity, mortality, and cost associated with MRSA infections in dialysis
      care.

PMID- 22150692
TI  - Urine and kidney cytokine profiles in experimental unilateral acute and chronic
      hydronephrosis.
AB  - OBJECTIVE: In search of potential urinary biomarkers of obstructive nephropathy,
      this study examined whether a potential change in the concentration of urinary
      cytokines [interferon-gamma(IFN-gamma), interleukin-1beta (IL-1beta), IL-2, IL-6,
      IL-10 and tumour necrosis factor-alpha (TNF-alpha)] reliably reflects changes in
      renal parenchymal levels of the same cytokines following the release of acute and
      chronic unilateral ureteral obstruction, respectively. MATERIAL AND METHODS:
      Acute obstruction was performed in 12 adult rats. After 48 h, six rats were used
      for selective urine collection and six rats had their kidneys removed and
      dissected into inner medulla and cortex. Chronic obstruction was performed in
      newborn rats. After 10 weeks, a similar set-up to that of the acute study was
      implemented. Sham-operated rats were prepared in parallel. Urine and tissue
      cytokines were measured with a bead-based multiplex sandwich immunoassay and
      analysed on a Luminex 100 IS instrument. RESULTS: In the acute study, there were
      significantly increased concentrations of IL-1beta and IL-6 in inner medulla and
      in urine from the obstructed kidney, significantly increased concentrations of
      TNF-alpha in urine from the obstructed kidney and, importantly, significantly
      increased levels of IL-10 in cortex and in urine from the non-obstructed kidney.
      In the chronic study, there were similar changes in IL-1beta and IL-6 (not
      significant) but no changes in TNF-alpha and IL-10. CONCLUSIONS: This study
      showed that inflammatory cytokines can be detected both in renal parenchyma and
      in urine from rats with experimental unilateral ureteral obstruction. Further
      studies are needed to confirm the diagnostic accuracy of IL-1beta, IL-6, IL-10
      and TNF-alpha in urine.

PMID- 22150693
TI  - Management of chronic spontaneous urticaria in real life--in accordance with the
      guidelines? A cross-sectional physician-based survey study.
AB  - BACKGROUND: Recently, the updated EAACI/GA(2) LEN/EDF/WAO guidelines for
      urticaria have been published. OBJECTIVE: To examine how chronic spontaneous
      urticaria (csU) patients in Germany are diagnosed and treated, and to compare the
      outcome to the guideline recommendations. METHODS: During this cross-sectional
      survey study, most dermatologists, paediatricians and 5149 general practitioners
      in private practice in Germany were asked to participate. All physicians who
      agreed were requested to complete a standardized questionnaire about their
      diagnostic and therapeutic management of csU. RESULTS: A total of 776
      questionnaires were available for analysis. Most physicians (82%) were attempting
      to identify underlying causes in their csU patients, but with only limited
      success. More than 70% reported to check for total serum IgE and to do skin prick
      testing (not suggested in first line by guideline). In contrast, only 10% applied
      the autologous serum skin test. The most common first-line treatments were non
      sedating antihistamines in standard or higher doses (as recommended). However,
      many physicians reported still using first generation sedating antihistamines
      (23%) (not recommended) or systemic steroids (18%). Experience with alternative
      options was low. Less than one-third of the participants reported to be familiar
      with the guidelines. Those who did, were found to be more likely to check for
      underlying causes, to be more experienced with antihistamine updosing and to be
      more reluctant to use sedating antihistamines or systemic steroids. CONCLUSION:
      The diagnostic and therapeutic management of csU by private practice physicians
      does not sufficiently comply with the guidelines. Awareness of the guidelines can
      lead to improved care.

PMID- 22150694
TI  - Time to first compression using Medical Priority Dispatch System compression
      first dispatcher-assisted cardiopulmonary resuscitation protocols.
AB  - INTRODUCTION: Without bystander cardiopulmonary resuscitation (CPR), cardiac
      arrest survival decreases 7%-10% for every minute of delay until defibrillation.
      Dispatcher-assisted CPR (D-CPR) has been shown to increase the rates of bystander
      CPR and cardiac arrest survival. Other reports suggest that the most critical
      component of bystander CPR is chest compressions with minimal interruption.
      Beginning with version 11.2 of the Medical Priority Dispatch System (MPDS)
      protocols, instructions for mouth-to-mouth ventilation (MTMV) and pulse check
      were removed and a compression-first pathway was introduced to facilitate rapid
      delivery of compressions. Additionally, unconscious choking and third-trimester
      pregnancy decision-making criteria were added in versions 11.3 and 12.0,
      respectively. However, the effects of these changes on time to first compression
      (TTFC) have not been evaluated. OBJECTIVE: We sought to quantify the TTFC of MPDS
      versions 11.2, 11.3, and 12.0 for all calls identified as cardiac arrest on call
      intake that did not require MTMV instruction. METHODS: Audio recordings of all D
      CPR events for October 2005 through May 2010 were analyzed for TTFC. Differences
      in TTFC across versions were compared using the Kruskal-Wallis test. RESULTS: A
      total of 778 cases received D-CPR. Of these, 259 were excluded because they met
      criteria for MTMV (pediatric patients, allergic reaction, etc.), were missing
      data, or were not initially identified as cardiac arrest. Of the remaining 519
      calls, the mean TTFC was 240 seconds, with no significant variation across the
      MPDS versions (p = 0.08). CONCLUSIONS: Following the removal of instructions for
      pulse check and MTMV, as well as other minor changes in the MPDS protocols, we
      found the overall TTFC to be 240 seconds with little variation across the three
      versions evaluated. This represents an improvement in TTFC compared with reports
      of an earlier version of MPDS that included pulse checks and MTMV instructions
      (315 seconds). However, the MPDS TTFC does not compare favorably with reports of
      older, non-MPDS protocols that included pulse checks and MTMV. Efforts should
      continue to focus on improving this key, and modifiable, determinant of cardiac
      arrest survival.

PMID- 22150695
TI  - Pontomedullary lacerations in falls from a height--a retrospective autopsy study.
AB  - Brainstem pontomedullary laceration (PML) in falls from a height appears as
      isolated cases and usually in feet-first impacts with a ring fracture. The aim of
      this study was to determine the frequency of PML in falls from a height, as well
      as the frequency of concomitant head and neck injuries. Out of 261 cases, PML was
      present in 40. An impact to the chin, as well as a feet- or buttocks-first
      impact, most often led to PML owing to transmission of the impact force. Also, a
      lateral, frontal, or posterior head impact, with subsequent hinge fracture, as
      well as the frontoposterior hyperextension of the head associated with an upper
      spine fracture, could be possible mechanisms of PML in falls from a height. The
      jawbone and other facial bones act as shock absorbers, and their fracture
      diminishes energy transfer toward the skull and protects the brain and brainstem
      from injury.

PMID- 22150696
TI  - Osteotome technique with injectable tissue-engineered bone and simultaneous
      implant placement by cell therapy.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effects of tissue
      engineered bone (TEB) on osteotome technique with simultaneous implant placement
      that is applied to the severe bone resorption in the maxilla for earlier bone
      regeneration and minimal invasive operation. MATERIAL AND METHODS: We applied
      injectable TEB, which was composed of bone marrow-derived mesenchymal stem cells
      (BMMSCs) as stem cell source and platelet-rich plasma as an autologous scaffold
      and signal molecules, with osteotome technique for 23 cases. After dental
      implants were pre-prepared with pilot drills and/or using the Summers Osteotome
      Kits, TEB was injected and followed by dental implants insertion. The outcomes
      were evaluated by radiographs. Statistical evaluation was performed by Friedman
      test and Wilcoxon signed-rank test (P <= 0.05). RESULTS: The grafted BMMSCs
      possessed a phenotype of mesenchymal stem cells. The lift-up bone height by TEB
      using BMMSCs showed the increase of 6.1 +/- 1.5 mm. Moreover, the mean
      regenerated bone height was 8.2 +/- 1.6 mm and 8.0 +/- 1.4 mm, and the average
      alveolar bone height was 15.6 +/- 1.2 mm and 15.1 +/- 1.4 mm, at 3 and 6 months,
      respectively. There were significant differences between pre-operative values and
      post-operative ones (at 3, 6 months). No perforations of the Schneider membrane
      were found and the inserted implants were successful after 1 year. CONCLUSIONS:
      This novel application using osteotome technique with injectable TEB would stably
      predict the success of bone formation and dental implants, and provide minimally
      invasive cell therapy.

PMID- 22150697
TI  - Feasibility of three-dimensional transthoracic echocardiography to evaluate right
      ventricular volumes in children and comparison to left ventricular values.
AB  - BACKGROUND: Three-dimensional echocardiography (3DE) allows accurate estimation
      of left ventricular (LV) volumes and function in children. Because of the
      peculiar morphology of the right ventricle (RV), RV volumes and function
      assessment remain challenging. 3D software adapted for RV morphology is a
      promising noninvasive method. AIMS: The aims of this study were to evaluate the
      feasibility of 3D RV analysis in a normal pediatric population and to compare 3D
      RV to 3D LV measurements. PATIENTS AND METHODS: 3D transthoracic echocardiography
      was performed in 50 patients (mean age 9.5 years +/- 5.1) with normal cardiac
      anatomy and function. Measurements were performed with the X3-1 or the X7-2
      matrix probe (iE33, Philips Medical Systems, Andover, MA, USA). Ventricular
      volumes were analyzed with dedicated analysis software (TomTec Imaging Systems,
      Munich, Germany). RESULTS: Measurements were possible in 100% of LVs and 94% of
      RVs. The stroke volumes of the two ventricles correlated well (r = 0.81 [95% CI,
      0.68-0.89], P < 0.0001) with a mean difference of 3.6 mL (+/-9.2). Compared to
      the LV, the RV had higher mean end-diastolic volume (53 mL [+/-29] versus 46 mL
      [+/-46], P = 0.020) and end-systolic volume (29 mL [+/-17] versus 17 mL [+/-12],
      P < 0.0001) but lower mean ejection fraction (49%[+/-8] versus 67%[+/-10], P <
      0.0001). CONCLUSION: 3DE using dedicated software is a feasible and reproducible
      method for RV volume quantification in children with normal hearts. Further
      studies are needed to validate the accuracy of the measurements.

PMID- 22150698
TI  - Early prediction of nasal continuous positive airway pressure failure in preterm
      infants less than 30 weeks gestation.
AB  - AIM: To predict early nasal continuous positive airway pressure failure within
      the first 2 h after birth in preterm infants. METHODS: Patient and respiratory
      support variables significantly associated with continuous positive airway
      pressure failure in the first 72 h after birth were identified in a cohort of
      preterm infants <30 weeks gestation. Using multivariable logistic regression
      analysis, risk estimates for early nasal continuous positive airway pressure
      failure were calculated. RESULTS: From 182 infants included, 62(34%) failed early
      nasal continuous positive airway pressure. Birth weight <=800 g, male gender and
      a fraction of inspired oxygen >0.25 at 1 and 2 h of age were significantly
      associated with early nasal continuous positive airway pressure failure.
      Combining these variables in a logistic regression model provided a minimal risk
      estimate for failure of 0.04[0.01-0.23] (female >800 g, FiO(2) <= 0.25 at 1, and
      2 h) and maximal estimate of 0.92[0.44-0.99] (male <=800 g, FiO(2) > 0.25 at 1
      and 2 h). CONCLUSION: Combining gender, birth weight and the fraction of inspired
      oxygen at 1 and 2 h of age allows for a better and more individualized prediction
      of early nasal continuous positive airway pressure failure in preterm infants
      less than 30 weeks gestation.

PMID- 22150701
TI  - Fumes from the spleen.

PMID- 22150702
TI  - Infant care practices related to sudden infant death syndrome in South Asian and
      White British families in the UK.
AB  - In the UK, infants of South Asian parents have a lower rate of sudden infant
      death syndrome (SIDS) than White British infants. Infant care and life style
      behaviours are strongly associated with SIDS risk. This paper describes and
      explores variability in infant care between White British and South Asian
      families (of Bangladeshi, Indian or Pakistani origin) in Bradford, UK (the vast
      majority of which were Pakistani) and identifies areas for targeted SIDS
      intervention. A cross-sectional telephone interview study was conducted involving
      2560 families with 2- to 4-month-old singleton infants enrolled in the Born in
      Bradford cohort study. Outcome measures were prevalence of self-reported
      practices in infant sleeping environment, sharing sleep surfaces, breast feeding,
      use of dummy or pacifier, and life style behaviours. We found that, compared with
      White British infants, Pakistani infants were more likely to: sleep in an adult
      bed (OR = 8.48 [95% CI 2.92, 24.63]); be positioned on their side for sleep (OR =
      4.42 [2.85, 6.86]); have a pillow in their sleep environment (OR = 9.85 [6.39,
      15.19]); sleep under a duvet (OR = 3.24 [2.39, 4.40]); be swaddled for sleep (OR
      = 1.49 [1.13, 1.97]); ever bed-share (OR = 2.13 [1.59, 2.86]); regularly bed
      share (OR = 3.57 [2.23, 5.72]); ever been breast-fed (OR = 2.00 [1.58, 2.53]);
      and breast-fed for 8+ weeks (OR = 1.65 [1.31, 2.07]). Additionally, Pakistani
      infants were less likely to: sleep in a room alone (OR = 0.05 [0.03, 0.09]); use
      feet-to-foot position (OR = 0.36 [0.26, 0.50]); sleep with a soft toy (OR = 0.52
      [0.40, 0.68]); use an infant sleeping bag (OR = 0.20 [0.16, 0.26]); ever sofa
      share (OR = 0.22 [0.15, 0.34]); be receiving solid foods (OR = 0.22 [0.17,
      0.30]); or use a dummy at night (OR = 0.40 [0.33, 0.50]). Pakistani infants were
      also less likely to be exposed to maternal smoking (OR = 0.07 [0.04, 0.12]) and
      to alcohol consumption by either parent. No difference was found in the
      prevalence of prone sleeping (OR = 1.04 [0.53, 2.01]). Night-time infant care
      therefore differed significantly between South Asian and White British families.
      South Asian infant care practices were more likely to protect infants from the
      most important SIDS risks such as smoking, alcohol consumption, sofa-sharing and
      solitary sleep. These differences may explain the lower rate of SIDS in this
      population.

PMID- 22150703
TI  - Factors affecting newborn care practices in Bangladesh.
AB  - Newborn care is of immense importance for the proper development and healthy life
      of a baby. Although child and infant mortality in South Asia has reduced
      substantially, the rate of neonatal mortality is still high, although these
      deaths can be prevented by adopting simple interventions at the community level.
      The aim of the study was to identify the associated factors which affect newborn
      care practices. Data for the study were drawn from the Bangladesh Demographic and
      Health Survey 2007, in which 6150 mothers were considered. The mean age of the
      mothers was 18 (+/-3.2) years. A little over 62% of the pregnant women received
      at least one antenatal check-up during the entire period of their pregnancy.
      About 70% of deliveries were conducted at home either by unskilled family members
      or by relatives. A clean instrument was used for cutting the cord of 87% of the
      newborn babies, while about 34% of them were reported to have had their first
      bath immediately after delivery. Initiation of breast feeding immediately after
      birth was practised in only about 19% of the cases. Compared with mothers with no
      education, those with secondary or higher levels were associated with clean cord
      care [odds ratio (OR) = 1.3, 95% confidence interval (CI) 1.0, 1.9] and early
      breast feeding [OR = 1.6, 95% CI 1.2, 2.2]. The study revealed an urgent need to
      educate mothers, and train traditional birth attendants and health workers on
      clean delivery practices and early neonatal care. Increasing the number of
      skilled birth attendants can be an effective strategy to increase safe delivery
      practices, and to reduce delivery complications.

PMID- 22150699
TI  - The molecular basis of herpes simplex virus latency.
AB  - Herpes simplex virus type 1 is a neurotropic herpesvirus that establishes latency
      within sensory neurones. Following primary infection, the virus replicates
      productively within mucosal epithelial cells and enters sensory neurones via
      nerve termini. The virus is then transported to neuronal cell bodies where
      latency can be established. Periodically, the virus can reactivate to resume its
      normal lytic cycle gene expression programme and result in the generation of new
      virus progeny that are transported axonally back to the periphery. The ability to
      establish lifelong latency within the host and to periodically reactivate to
      facilitate dissemination is central to the survival strategy of this virus.
      Although incompletely understood, this review will focus on the mechanisms
      involved in the regulation of latency that centre on the functions of the virus
      encoded latency-associated transcripts (LATs), epigenetic regulation of the
      latent virus genome and the molecular events that precipitate reactivation.

PMID- 22150704
TI  - Prediction of childhood obesity by infancy weight gain: an individual-level meta
      analysis.
AB  - To assess the predictive ability of infant weight gain on subsequent obesity we
      performed a meta-analysis of individual-level data on 47,661 participants from 10
      cohort studies from the UK, France, Finland, Sweden, the US and Seychelles. For
      each individual, weight SD scores at birth and age 1 year were calculated using
      the same external reference (British 1990). Childhood obesity was defined by
      International Obesity Task Force criteria. Each +1 unit increase in weight SD
      scores between 0 and 1 year conferred a twofold higher risk of childhood obesity
      (odds ratio = 1.97 [95% confidence interval (CI) 1.83, 2.12]), and a 23% higher
      risk of adult obesity (odds ratio = 1.23 [1.16, 1.30]), adjusted for sex, age and
      birthweight. There was little heterogeneity between studies. A risk score for
      childhood obesity comprising weight gain 0-1 year, mother's body mass index,
      birthweight and sex was generated in a random 50% selection of individuals from
      general population cohorts with available information (n = 8236); this score
      showed moderate predictive ability in the remaining 50% sample (area under
      receiving operating curve = 77% [95% CI 74, 80%]). A separate risk score for
      childhood overweight showed similar predictive ability (area under receiving
      operating curve = 76% [73, 79%]). In conclusion, infant weight gain showed a
      consistent positive association with subsequent obesity. A risk score combining
      birthweight and infant weight gain (or simply infant weight), together with
      mother's body mass index and sex may allow early stratification of infants at
      risk of childhood obesity.

PMID- 22150705
TI  - Associations between grip strength of parents and their 4-year-old children:
      findings from the Southampton Women's Survey.
AB  - Relationships between birthweight and grip strength throughout the life course
      suggest that early influences on the growth and development of muscle are
      important for long-term muscle function. However, little is known about parental
      influences on children's grip strength. We have explored this in the Southampton
      Women's Survey, a prospective general population cohort study from before
      conception through childhood. Grip strength was measured using a Jamar handgrip
      dynamometer in the mother at 19 weeks' gestation and her partner, and in the
      child at age 4 years. Pre-pregnancy heights and weights were measured in the
      mothers; reported weights and measured heights were available for the fathers.
      Complete data on parents and children were available for 444 trios. In
      univariable analyses, both parents' grip strengths were significantly associated
      with that of the child (r = 0.17, P < 0.001 for mothers; r = 0.15, P = 0.002 for
      fathers). These correlations were similar to that between the grip strength of
      the mothers and the fathers (r = 0.17, P < 0.001). In the multivariable model,
      after adjustment for child's height and physical activity, the correlations with
      the child's grip strength were attenuated, being 0.10 (P = 0.02) and 0.11 (P =
      0.01) for mothers' and fathers' grip strength respectively. The findings show
      that grip strength of each parent is associated with that of the child,
      indicating that heritable influences and the shared family environment influence
      the development of muscle strength. This contributes to our understanding of the
      role of heritable and environmental factors on early muscle growth and
      development, which are important for muscle function across the life course.

PMID- 22150706
TI  - Intrauterine growth and postnatal skeletal development: findings from the
      Southampton Women's Survey.
AB  - We have previously demonstrated associations between fetal growth in late
      pregnancy and postnatal bone mass. However, the relationships between the
      intrauterine and early postnatal skeletal growth trajectory remain unknown. We
      addressed this in a large population-based mother-offspring cohort study. A total
      of 628 mother-offspring pairs were recruited from the Southampton Women's Survey.
      Fetal abdominal circumference was measured at 11, 19 and 34 weeks gestation using
      high-resolution ultrasound with femur length assessed at 19 and 34 weeks. Bone
      mineral content was measured postnatally in the offspring using dual-energy X-ray
      absorptiometry at birth and 4 years; postnatal linear growth was assessed at
      birth, 6, 12, 24, 36 and 48 months. Late pregnancy abdominal circumference growth
      (19-34 weeks) was strongly (P < 0.01) related to bone mass at birth, but less
      robustly associated with bone mass at 4 years. Early pregnancy growth (11-19
      weeks) was more strongly related to bone mass at 4 years than at birth. Postnatal
      relationships between growth and skeletal indices at 4 years were stronger for
      the first and second postnatal years, than the period aged 2-4 years. The
      proportion of children changing their place in the distribution of growth
      velocities progressively reduced with each year of postnatal life. The late
      intrauterine growth trajectory is a better predictor of skeletal growth and
      mineralisation at birth, while the early intrauterine growth trajectory is a more
      powerful determinant of skeletal status at age 4 years. The perturbations in this
      trajectory which influence childhood bone mass warrant further research.

PMID- 22150707
TI  - Maternal ethnicity and pre-eclampsia in New York City, 1995-2003.
AB  - Studies on ethnic differences in the risk of pre-eclampsia are limited. We linked
      birth records for 902,460 singleton births for the period 1995-2003 in New York
      City with hospital discharge data to evaluate the association between ethnicity
      and the risk of pre-eclampsia and compare risks between US-born and foreign-born
      women. Logistic regression models adjusted for maternal age, maternal education,
      parity, self-reported pre-pregnancy maternal weight, smoking during pregnancy and
      year of delivery were used to compare each ethnic group with non-Hispanic White
      women. The prevalence of pre-eclampsia in this study population was 3.2%. Among
      the major ethnic groups considered in our study, East Asian women had the lowest
      risk of pre-eclampsia (1.4%) and Mexican women had the highest risk (5.0%).
      Compared with non-Hispanic White women, there was a slightly decreased risk for
      East Asian women (adjusted OR = 0.8, [95% CI 0.7, 0.8]), similar risk for North
      African women (adjusted OR = 1.1, [95% CI 0.9, 1.3]), and increased risk for all
      other major ethnic groups (adjusted ORs: 1.3, 2.9), with the highest risk for
      Mexican women (adjusted OR = 2.9, [95% CI 2.7, 3.1]). No difference in risks was
      observed for US- vs. foreign-born women with the exception that foreign-born
      South-East Asian and Pacific Islanders had an increased risk of pre-eclampsia
      (adjusted OR = 1.8, [95% CI 1.0, 3.1]) relative to those born in the US. We
      concluded that there was ethnic heterogeneity in the development of pre-eclampsia
      among women in New York City and that Asian subgroups should be examined
      separately in future studies on ethnicity. Our results should contribute to
      screening for pre-eclampsia taking ethnic variation into account, and may help to
      suggest leads for the study of the aetiology of the condition.

PMID- 22150708
TI  - Vitamin D deficiency in pregnant women and their neonates in spring time in
      western Turkey.
AB  - Although Turkey is located in a sunny region, vitamin D deficiency is still a
      serious health problem in pregnant women and their infants, especially among the
      low socio-economic status Turkish population. This study was carried out in order
      to measure serum 25-hydroxyvitamin D3 [25(OH)D] concentrations of the pregnant
      women in the last trimester and in their neonates at delivery and to determine
      the factors associated with maternal serum 25(OH)D concentrations. Among the
      patients visiting the Ege Obstetrics and Gynecology Hospital in the period March
      to May 2008, 258 healthy pregnant women >=37 weeks of gestation were included in
      this study. The information on different characteristics such as the number of
      pregnancies and births, nutritional status, vitamin and mineral support during
      gestation, educational status, clothing style and the economic level of the
      family was collected from women. Blood samples from the mothers and umbilical
      cord of the newborns were taken to measure 25(OH)D. The mean 25(OH)D
      concentrations of the mothers and their infants were 11.5 +/- 5.4 ng/mL and 11.5
      +/- 6.8 ng/mL, respectively. We found a strong positive correlation between
      maternal serum and umbilical cord blood 25(OH)D concentrations (r = 0.651, P <
      0.001). The concentration of 25(OH)D was <=20 ng/mL in 233 mothers (90.3%) and
      <=10 ng/mL in 130 mothers (50.4%). Maternal serum 25(OH)D concentrations related
      strongly to factors such as uncovered dressing style, sufficient consumption of
      dairy products and multivitamin use during gestation (P < 0.05). About half
      (52.7%) of these women had a covered dressing style. 25(OH)D concentrations of
      these covered dressing mothers and their infants were 9.7 +/- 5.1 ng/mL and 9.7
      +/- 5.6 ng/mL, respectively, which were significantly lower compared with those
      of uncovered mothers and their babies (P < 0.001). This study showed that,
      despite a sunny environment, vitamin D deficiency and insufficiency are highly
      prevalent among the mothers and their neonates. This is generally due to the life
      style and nutritional status of the mothers. These findings suggest that much
      more effective vitamin D prophylaxis programmes should be implemented for
      pregnant women as well as for their babies.

PMID- 22150709
TI  - Blood lead levels and associated sociodemographic factors among preschool
      children in the South Eastern region of China.
AB  - Children are especially vulnerable to lead toxicity, and exposure to lead has
      been linked to poor school performance and delinquency in children and
      adolescents. Even low-level lead exposure [blood lead level (BLL) <10 ug/dL] can
      cause intellectual deficit. In China, BLLs in children decreased slightly after
      the phasing out of lead in gasoline, but few studies have examined the
      sociodemographic factors associated with BLL above 10 ug/dL. In this study, we
      sought to examine the hypothesis that sociodemographic factors predict BLLs. We
      measured BLLs of 1344 preschool children (3-5 years old) from the China Jintan
      Child Cohort Study. Children's sociodemographic and health statuses, as well as
      parental sociodemographic data, were collected using questionnaires. Regression
      models were used to explore the association between sociodemographic factors and
      log-transformed BLLs as well as the relationship between sociodemographic factors
      and the risk of BLL >=10 ug/dL. We found the median BLL to be 6.2 ug/dL (range:
      1.8-32.0 ug/dL); 8% of children had BLLs >=10 ug/dL. Boys had a higher median BLL
      (6.4 ug/dL) than girls and were more likely to have BLL >=10 ug/dL [odds ratio =
      1.77, 95% confidence interval 1.14, 2.74]. BLLs increased as children aged, with
      a median BLL of 6.6 ug/dL among 5-year-old children. Children with siblings had a
      higher average BLL and greater prevalence of a BLL >=10 ug/dL than those without
      siblings. Living in a crowded neighbourhood was also associated with increased
      BLLs. Mother's lower education, father's occupation (as professional worker) and
      parental smoking at home were associated with increased BLLs. This study shows
      that children in this area still have relatively high BLLs even after the phasing
      out of leaded gasoline. Both children's and parental factors and community
      condition are associated with increased BLLs. Future efforts are needed to
      identify other sources of exposure and develop targeted prevention strategies.

PMID- 22150710
TI  - Association of self-reported passive smoking in pregnant women with cotinine
      level of maternal urine and umbilical cord blood at delivery.
AB  - Passive smoking during pregnancy leads to adverse effects on mother and infant.
      The present investigation was designed to evaluate the association between
      maternal reported passive smoking with the cotinine concentration of maternal
      urine and umbilical cord blood at delivery and to determine the accuracy of
      maternal reporting of exposure to cigarette smoke during pregnancy. This was a
      cross-sectional study. From the 108 non-smoker pregnant women who were referred
      for delivery, 54 were passive smokers. Urine samples were collected from the
      mothers in the delivery room and blood samples after birth were taken from the
      umbilical cord. Passive smoking was evaluated through questionnaire and cotinine
      level of urine and umbilical cord blood. The geometric mean cotinine
      concentration of the maternal urine and the umbilical cord serum were,
      respectively, 27.4 +/- 29.96 ng/mL and 3.71 +/- 1.22 ng/mL in the exposed group
      (P < 0.001) and 0.75 +/- 2.29 and 0.40 +/- 0.63 in the non-exposed group (P <
      0.001). There was a statistically significant correlation between maternal
      urinary and umbilical cord serum level of cotinine (P < 0.001, r = 0.58).
      Significant associations were shown between maternal reports of exposure to
      cigarette smoking with cotinine level of urine (kappa = 96%) and umbilical cord
      (kappa = 98%) (P < 0.001). This study shows that the pregnant woman's report of
      passive smoking during pregnancy in Iran is accurate. The questionnaire is an
      appropriate method to evaluate smoke exposure and could replace cotinine
      measurement.

PMID- 22150711
TI  - Husband's preference for a son and women's nutrition: examining the role of
      actual and desired family composition on women's anaemia and body mass index in
      India.
AB  - This study examines the relationship between the husband's preference for a son,
      sex composition of children and risk of anaemia and underweight among married
      Indian women. Information was collected regarding 29,517 couples having at least
      one child in the nationally representative 2005-06 National Family Health Survey
      of India. The exposures were husband's preference for a son and sex composition
      of children: sons only, daughters only and mixed. Outcome included maternal
      underweight and moderate/severe anaemia. Husband's preference for a son was not
      found to be associated with his wife's risk of anaemia or underweight. Sex
      composition of the children was modestly associated with increased odds of
      anaemia among women from households with daughters only as compared with those
      with sons only [AOR: 1.19; 95% CI 1.04, 1.35]. The findings from this population
      based study of socio-cultural norms around preference for a son and married
      Indian women's nutritional status do not support the hypothesis that husband's
      preference for sons influences the nutritional status of their wives. However,
      having daughters only is associated with maternal anaemia for reasons that remain
      to be established.

PMID- 22150712
TI  - Investigation into the use of short message services to expand uptake of human
      immunodeficiency virus testing, and whether content and dosage have impact.
AB  - OBJECTIVE: South Africa has one of the highest human immunodeficiency virus (HIV)
      prevalence rates in the world, but despite the well-established benefits of HIV
      counseling and testing (HCT), there is low uptake of HCT. The study aimed to
      investigate the effectiveness of using short message services (SMSs) to encourage
      HCT while interrogating the impact of altering SMS content and dosage (the number
      of SMSs). MATERIALS AND METHODS: About 2,533 participants were recruited via an
      SMS sent to 24,000 mobiles randomly sampled from a pre-existing database.
      Recruits were randomly allocated to four intervention groups that received 3 or
      10 informational (INFO) or motivational (MOTI) SMSs, and a control group. After
      the intervention, participants were prompted to go for HCT, and postintervention
      assessment was done after 3 weeks. RESULTS: In comparison with the control,
      receipt of 10 MOTI messages had the most impact on uptake of HCT with a 1.7-fold
      increased odds of testing (confidence interval 95%; p=0.0036). The lack of
      efficacy of three SMSs indicates a threshold effect, that is, a minimum number of
      MOTI SMSs is required. INFO SMSs, whether 3 or 10 were sent, did not have a
      statistically significant effect. The cost can be calculated for the marginal
      effect of the SMSs, that is, the cost to get people to test over and above those
      who were likely to test without the intervention. Use of 10 MOTI SMSs yielded a
      cost-per-tester of $2.41. CONCLUSIONS: While there are methodological issues
      apparent in our study, the results demonstrate the potential of SMSs to influence
      the uptake of HCT, the importance of appropriate content, and the need to
      determine a threshold for SMS-based interventions. These results indicate a
      potential for SMSs to be used more generally for interventions encouraging people
      to take health-related actions, and the need for further research in this field.
      The reasonable cost-per-tester is promising for the scale-up of such an
      intervention.

PMID- 22150713
TI  - Retrospective return on investment analysis of an electronic treatment adherence
      device piloted in the Northern Cape Province.
AB  - OBJECTIVE: The return on investment (ROI) for utilizing the SIMpill electronic
      treatment adherence solution as an adjunct to directly observed treatment short
      course (DOTS) is assessed using data from a 2005 pilot of the SIMpill solution
      among new smear-positive tuberculosis (TB) patients in the Northern Cape
      Province. The value of this cost minimization analysis (CMA), for use by public
      health planners in low-resource settings as a precursor to more rigorous
      assessment, is discussed. MATERIALS AND METHODS: The retrospective analysis
      compares the costs and health outcomes of the DOTS-SIMpill cohort with DOTS-only
      controls. Hypothetical 5-year cash flows are generated and discounted to estimate
      net present values (NPVs). RESULTS: Comparison between the DOTS-SIMpill pilot
      cohort and DOTS-only supported controls, for a hypothetical implementation of
      1,000 devices, over 5 years, demonstrates positive ROI for the DOTS-SIMpill
      cohort based on improved health outcomes and reduced average cost per patient.
      The net stream is shown to be positive from the first year. Discounted NPV is ZAR
      3,255,256 (US$ 493,221) for a cohort that would have started mid 2005 and ZAR
      3,747,636 (US$ 487,339) starting mid 2010. This is an ROI of 23% over the 5-year
      period. CONCLUSION: The addition of electronic treatment adherence support
      technology can help to improve TB outcomes and lower average cost per patient by
      reducing treatment failure and the associated higher cost and burden on limited
      resources. CMA is an appropriate initial analysis for health planners to
      highlight options that may justify more sophisticated methods such as cost
      effectiveness analysis or full cost benefit analysis where a preferred option is
      immediately revealed. CMA is proposed as a tool for use by public health planners
      in low-resource settings to evaluate the ROI of treatment adherence technology
      postpilot and prior to implementation.

PMID- 22150714
TI  - Building the capacity to build capacity in e-health in sub-Saharan Africa: the
      KwaZulu-Natal experience.
AB  - BACKGROUND: Sub-Saharan Africa has a disproportionate burden of disease and an
      extreme shortage of health workers. There are already too few doctors to train
      doctors in specialities and sub-specialties. E-health is seen as a possible
      solution through distance education, telemedicine, and computerized health
      information systems but there are few people trained in e-health. We describe 12
      years of experience at the University of KwaZulu-Natal (UKZ-N) in education and
      training in postgraduate medical disciplines, medical informatics, and
      telemedicine. MEDICAL EDUCATION: Videoconferencing of seminars and grand rounds
      to regional training hospitals commenced in 2001 and has grown to 40 h of
      interactive conferencing taking place weekly during academic terms involving over
      33,000 participants in 2010. Videoconferenced sessions are directly recorded to
      DVD and DVDs are sent to other medical schools in Africa that do not have the
      infrastructure to directly connect. E-HEALTH EDUCATION: Students and academic
      staff were initially sent to the United States for training in medical
      informatics and workshops were held in South Africa for people from sub-Saharan
      Africa. This led to the development of postgraduate academic programs in medical
      informatics and telemedicine at UKZ-N. African students were then brought to UKZ
      N for training. The model was changed from UKZ-N to students and staff based at
      their home universities with the aim of building capacity in the staff at partner
      institutions so that they can in time offer their own e-health academic programs.
      CONCLUSIONS: The need for capacity development in all aspects of e-health in sub
      Saharan Africa is great and innovative solutions are required.

PMID- 22150715
TI  - Cardiac surgery in patients with Gilbert's syndrome.
AB  - We report the case of a 58-year-old patient with Gilbert's syndrome and multiple
      cardiovascular pathologies, including aortic regurgitation with a dilated aortic
      root, severe mitral regurgitation, and chronic atrial fibrillation. A Bentall
      procedure, mitral valve repair, and modified radiofrequency MAZE procedure were
      performed. The management of Gilbert's syndrome in patients undergoing cardiac
      surgery is reviewed.

PMID- 22150717
TI  - Food and addiction: implications and relevance to eating disorders and obesity.

PMID- 22150716
TI  - Enhancement of Helicobacter pylori outer inflammatory protein DNA vaccine
      efficacy by co-delivery of interleukin-2 and B subunit heat-labile toxin gene
      encoded plasmids.
AB  - Development of an effective vaccine for controlling H. pylori-associated
      infection, which is present in about half the people in the world, is a priority.
      The H. pylori outer inflammatory protein (oipA) has been demonstrated to be a
      potential antigen for a vaccine. In the present study, use of oipA gene encoded
      construct (poipA) for C57BL/6 mice vaccination was investigated. Whether co
      delivery of IL-2 gene encoded construct (pIL-2) and B subunit heat-labile toxin
      of Escherichia coli gene encoded construct (pLTB) can modulate the immune
      response and enhance DNA vaccine efficacy was also explored. Our results
      demonstrated that poipA administered intradermally ('gene gun' immunization)
      promoted a strong Th2 immune response, whereas co-delivery of either pIL-2 or
      pLTB adjuvant elicited a Th1-biased immune response. PoipA administered with both
      pIL-2 and pLTB adjuvants promoted a strong Th1 immune response. Regardless of the
      different immune responses promoted by the various vaccination regimes, all
      immunized mice had smaller bacterial loads after H. pylori challenge than did PBS
      negative and pVAX1 mock controls. Co-delivery of adjuvant(s) enhances poipA DNA
      vaccine efficacy by shifting the immune response from being Th2 to being Th1
      biased, which results in a greater reduction in bacterial load after H. pylori
      challenge. Both prophylactic and therapeutic vaccination can achieve sterile
      immunity in some subjects.

PMID- 22150718
TI  - Value-based insurance design: more health at any price.
AB  - When everyone is required to pay the same out-of-pocket amount for health care
      services regardless of clinical indication, there is evidence of underuse of high
      value services and overuse of interventions of no or marginal clinical benefit.
      Unlike most current health plan designs, value-based insurance design (V-BID)
      acknowledges heterogeneity of clinical interventions and patient characteristics.
      It encourages the use of services with strong evidence of clinical benefit and
      likewise discourages the use of low-value services. Implementing this concept
      into the national policy debate required a strategy that included conceptual
      framework development, program implementation, rigorous evaluation, media
      outreach, and an advocacy plan. Upon completion of this strategy involving
      several colleagues from multiple disciplines, Congress included language
      specifically authorizing V-BID in the Patient Protection and Affordable Care Act.
      A wide-ranging approach, planned as early as possible, can lead to the successful
      translation of health services research to policy.

PMID- 22150719
TI  - Evidence that the Agr-like quorum sensing system regulates the toxin production,
      cytotoxicity and pathogenicity of Clostridium perfringens type C isolate CN3685.
AB  - Clostridium perfringens possesses at least two functional quorum sensing (QS)
      systems, i.e. an Agr-like system and a LuxS-dependent AI-2 system. Both of those
      QS systems can reportedly control in vitro toxin production by C. perfringens but
      their importance for virulence has not been evaluated. Therefore, the current
      study assessed whether these QS systems might regulate the pathogenicity of
      CN3685, a C. perfringens type C strain. Since type C isolates cause both
      haemorrhagic necrotic enteritis and fatal enterotoxemias (where toxins produced
      in the intestines are absorbed into the circulation to target other internal
      organs), the ability of isogenic agrB or luxS mutants to cause necrotizing
      enteritis in rabbit small intestinal loops or enterotoxemic lethality in mice was
      evaluated. Results obtained strongly suggest that the Agr-like QS system, but not
      the LuxS-dependent AI-2 QS system, is required for CN3685 to cause haemorrhagic
      necrotizing enteritis, apparently because the Agr-like system regulates the
      production of beta toxin, which is essential for causing this pathology. The Agr
      like system, but not the LuxS-mediated AI-2 system, was also important for CN3685
      to cause fatal enterotoxemia. These results provide the first direct evidence
      supporting a role for any QS system in clostridial infections.

PMID- 22150720
TI  - Does longitudinal strain predict left ventricular remodeling after myocardial
      infarction?
AB  - BACKGROUND: One of the most prognostically significant consequences of acute
      myocardial infarction (AMI) is the development of an adverse left ventricular
      (LV) remodeling. OBJECTIVES: The purpose of our study was to evaluate a
      feasibility of speckle tracking imaging (STI), in particular, global longitudinal
      strain (Ls) in predicting LV remodeling after AMI. METHODS: A total of 82 AMI
      patients (mean age 57.6 +/- 9.4) were included in the study. Within 48-72 hours
      of the onset of AMI and at a 4-month follow-up, two-dimensional echocardiography
      was performed. The apical two- and four-chamber views of the heart were analyzed
      offline using Echo Pac software for the assessment of strain by the STI method.
      LV remodeling was defined as a 15% increase from the baseline in LV end-diastolic
      volume. RESULTS: Twenty-eight patients (34.1%) with LV remodeling at 4-month
      follow-up had comparable baseline clinical and echocardiographic characteristics
      with 54 patients (without LV remodeling), except for a predominance of the
      anterior wall MI (P < 0.01), higher leukocyte count value at admission (P <
      0.01), lower ejection fraction (P < 0.05), increased end-systolic volume (P <
      0.05), and reduced global systolic Ls (P < 0.05). Multivariable logistic
      regression analysis revealed the systolic Ls as an independent determinant of LV
      remodeling after AMI. A receiver operating characteristic curve analysis showed
      that a cutoff value of -11.6% for the systolic Ls yielded a 78% sensitivity and a
      73% specificity to predict LV remodeling in 4 months. CONCLUSIONS: Our study has
      shown that LV longitudinal strain assessed by STI is an independent predictor of
      LV remodeling after AMI.

PMID- 22150721
TI  - Chain binomial models and binomial autoregressive processes.
AB  - We establish a connection between a class of chain-binomial models of use in
      ecology and epidemiology and binomial autoregressive (AR) processes. New results
      are obtained for the latter, including expressions for the lag-conditional
      distribution and related quantities. We focus on two types of chain-binomial
      model, extinction-colonization and colonization-extinction models, and present
      two approaches to parameter estimation. The asymptotic distributions of the
      resulting estimators are studied, as well as their finite-sample performance, and
      we give an application to real data. A connection is made with standard AR
      models, which also has implications for parameter estimation.

PMID- 22150722
TI  - ADH1B polymorphism, alcohol consumption, and binge drinking in Slavic Caucasians:
      results from the Czech HAPIEE study.
AB  - BACKGROUND: Several genetic polymorphisms influence the risk of heavy alcohol
      consumption but it is not well understood whether the genetic effects are similar
      in different populations and drinking cultures, nor whether the genetic
      influences on binge drinking are similar to those seen for alcoholism. METHODS:
      We have analyzed the effect of the Arg47His (rs1229984) variant within the
      alcohol dehydrogenase (ADH1B) gene on a range of drinking related variables in a
      large Eastern European Slavic population (Czech HAPIEE study), which recruited
      random samples of men and women aged 45-69 years in 7 Czech towns (3,016 males
      and 3,481 females with complete data). Drinking frequency, annual alcohol intake,
      prevalence of binge drinking (>=100 g in men and >=60 g in women at least once a
      month) and the mean dose of alcohol per occasion were measured by the graduated
      frequency questionnaire. Alcohol intake in a typical week was used to define
      heavy drinking (>=350 g/wk in men and >=210 g in women). Problem drinking (>=2
      positive answers on CAGE) and negative consequences of drinking on different
      aspects of life were also measured. RESULTS: The frequency of the His47 allele
      carriers was 11%. Homozygotes in the common allele (Arg47Arg), among both males
      and females, had significantly higher drinking frequency, and annual and weekly
      intake of alcohol than His47 carriers. The odds ratio of heavy drinking in
      Arg47Arg homozygotes versus His47 carriers was 2.1 (95% confidence intervals 1.1
      3.2) in men and 2.2 (1.0-4.7) in women. In females, but not in males, Arg47Arg
      homozygotes had marginally significantly higher prevalence of binge drinking and
      mean alcohol dose per drinking session. There was no consistent association with
      problem drinking and negative consequences of drinking. CONCLUSIONS: The ADH1B
      genotype was associated with the frequency and volume of drinking but its
      associations with binge drinking and problem drinking were less consistent.

PMID- 22150723
TI  - The adhesion of oral bacteria to modified titanium surfaces: role of plasma
      proteins and electrostatic forces.
AB  - OBJECTIVES: Modifications of titanium (Ti) implant surfaces have a significant
      effect on early biofilm formation and the outcome of implant procedures. The aim
      of this study was to examine the role of plasma proteins and electrostatic forces
      in the adhesion mechanism of oral bacteria to modified Ti surfaces. MATERIALS AND
      METHODS: Ti discs with three different types of surface modifications, machined,
      acid-etched, and acid-etched and blasted, were examined for adhesion of oral
      bacteria: Streptococcus mutans, Porphyromonas gingivalis, and Fusobacterium
      nucleatum. Following pretreatment of the Ti with ion rich solutions or coating by
      human serum albumin or fibronectin, bacterial adhesion was examined by scanning
      electron microscopy and assessed quantitatively by DNA analysis. Ti coating by
      proteins as well as bacterial adhesion and their interrelationships were further
      investigated through confocal scanning laser microscopy. RESULTS: Acid-etched and
      blasted Ti surfaces exhibited significantly higher amounts of bacteria adhesion
      than the other two surfaces. Calcium was found to serve as a bridging agent in
      the adhesion process of S. mutans and F. nucleatum to Ti surfaces. Although
      albumin coating of the Ti reduced the adhesion of S. mutans to all surfaces, it
      had no influence on the adhesion of P. gingivalis or F. nucleatum. Coating the Ti
      with fibronectin enhanced P. gingivalis and F. nucleatum adhesion. CONCLUSIONS:
      Bacterial adhesion to Ti surfaces is roughness-dependent, and the adhesion
      mechanism is influenced by ions and proteins of the initial coating derived from
      the blood.

PMID- 22150724
TI  - Increased serum concentrations of adhesion molecules but not of chemokines in
      patients with Type 2 diabetes compared with patients with Type 1 diabetes and
      latent autoimmune diabetes in adult age: action LADA 5.
AB  - AIMS: Systemic concentrations of adhesion molecules and chemokines are associated
      with increased risk of cardiovascular complications. We compared these factors
      between patients with Type 2 diabetes vs. Type 1 diabetes or latent autoimmune
      diabetes in adults. METHODS: Serum concentrations of adhesion molecules sE
      selectin, sICAM-1 and sVCAM-1, and chemokines CCL2, CCL3 and CCL4 were measured
      in 61 patients with latent autoimmune diabetes in adults, 90 with Type 1
      diabetes, 465 with Type 2 diabetes and in 41 control subjects, using multiple
      regression models to adjust for possible confounders. RESULTS: Patients with Type
      2 diabetes exhibited greater concentrations of adhesion molecules (P < 0.02) than
      those with Type 1 diabetes, latent autoimmune diabetes in adults and control
      subjects. These differences persisted upon adjustments for age, sex, BMI, blood
      pressure and diabetes duration (P < 0.04). Higher BMI positively correlated with
      concentrations of adhesion molecules in all subjects (P < 0.0001). Concentrations
      of sE-selectin positively related to diastolic (beta = 0.31) and systolic (beta =
      0.28) blood pressure in the adjusted model (P < 0.04). Concentrations of the
      chemokines, CCL2 and CCL4, did not differ between groups, while CCL3 was higher
      in patients with latent autoimmune diabetes in adults and Type 1 diabetes than in
      those with Type 2 diabetes and control subjects (P < 0.05). CONCLUSIONS: Systemic
      concentrations of adhesion molecules, but not chemokines, relate to
      cardiovascular risk factors, but remain higher after adjustments in Type 2
      diabetes, suggesting a diabetes-type specific effect without difference between
      latent autoimmune diabetes in adults and Type 1 diabetes, despite their
      dissimilar phenotype.

PMID- 22150725
TI  - Plugging practice leaks.

PMID- 22150726
TI  - EHRs: watching and waiting.

PMID- 22150727
TI  - Employed physicians: lower productivity but higher quality of care?

PMID- 22150728
TI  - ACO costs may outweigh savings.

PMID- 22150729
TI  - ACO costs may outweigh savings.

PMID- 22150730
TI  - Simple tools to increase patient satisfaction with the referral process.

PMID- 22150731
TI  - Rethinking your approach to prescription "refills".

PMID- 22150732
TI  - Is your practice at risk for fraud?

PMID- 22150733
TI  - Communicating bad news to your patients.

PMID- 22150744
TI  - A day in my practice in 2020.

PMID- 22150745
TI  - Central sleep apnea is associated with increased risk of ischemic stroke in the
      elderly.
AB  - OBJECTIVES: Sleep apnea/hypopnea syndrome is a well-recognized independent risk
      factor for stroke in middle-aged population, but controversy remains in older
      subjects. We examined the possible association between different respiratory
      parameters and risk of stroke in a prospective population-based cohort of 394
      stroke-free elderly subjects. MATERIAL AND METHODS: Fully overnight
      polysomnography was performed at baseline. Over the 6 year follow-up period, 20
      ischemic strokes occurred. Differences in stroke-free survival between subjects
      according to central apnea index (CAI) were assessed. RESULTS: We just observed
      association with incident ischemic stroke on central sleep apnea (CSA) episodes.
      Obstructive sleep apnea, time passed under 90% oxygen saturation, or arousal
      index were not associated. The event-free survival was lowest in the highest CAI
      group. This association was independent of any other vascular risk factors.
      CONCLUSIONS: CSA is the specific respiratory event associated with stroke in the
      elderly. Additionally, CSA could be a marker of silent brain ischemia, as a sign
      of disturbed regulation of central respiratory mechanisms, tentatively of
      ischemic origin.

PMID- 22150746
TI  - Role of renal medullary oxidative and/or carbonyl stress in salt-sensitive
      hypertension and diabetes.
AB  - 1. Salt-sensitive hypertension is commonly associated with diabetes, obesity and
      chronic kidney disease. The present review focuses on renal mechanisms involved
      in the development of this type of hypertension. 2. The renal medullary
      circulation plays an important role in the development of salt-sensitive
      hypertension. In vivo animal studies have demonstrated that the balance between
      nitric oxide (NO) and reactive oxygen species (ROS) in the renal medulla is an
      important element of salt-sensitive hypertension. The medullary thick ascending
      limb (mTAL) in the outer medulla is an important source of NO and ROS production
      and we have explored the mechanisms that stimulate their production, as well as
      the effects of NO superoxide and hydrogen peroxide on mTAL tubular sodium
      reabsorption and the regulation of medullary blood flow. 3. Angiotensin II
      stimulated NO produced in the mTAL is able to diffuse from the renal mTAL to the
      surrounding vasa recta capillaries, providing a mechanism by which to increase
      medullary blood flow and counteract the direct vasoconstrictor effects of
      angiotensin II. Enhanced oxidative stress attenuates NO diffusion in this region.
      4. Carbonyl stress, like oxidative stress, can also play an important role in the
      pathogenesis of chronic kidney disease, such as insulin resistance, salt
      sensitive hypertension and renal vascular complications. 5. Despite the large
      number of studies undertaken in this area, there is as yet no drug available that
      directly targets renal ROS. Oxidative and/or carbonyl stress may be the next
      target of drug discovery to protect against salt-sensitive hypertension and
      associated end-organ damage.

PMID- 22150747
TI  - Reducing the incidence of TRALI in the UK: the results of screening for donor
      leucocyte antibodies and the development of national guidelines.
AB  - BACKGROUND AND OBJECTIVES:   Transfusion-related acute lung injury (TRALI) is
      associated with the passive transfusion of leucocyte antibodies in blood
      products. Blood Transfusion Services have adopted a number of different
      strategies for reducing the incidence of TRALI, but, while these have been
      successful, TRALI has not been completely eliminated. Many Transfusion Services
      have introduced leucocyte antibody screening of donors to further reduce TRALI.
      This report describes the results of donor leucocyte antibody screening within
      NHS Blood and Transplant and the guidelines that have been developed for
      Transfusion Services within the United Kingdom (UK) to reduce the incidence of
      TRALI. MATERIALS AND METHODS:   Blood samples from newly recruited female
      apheresis donors were tested for human leucocyte antigens (HLA) class I and class
      II antibodies and granulocyte-specific antibodies. RESULTS:   A total of 1157
      female donors were evaluated. Three hundred and fifteen (27.23%) donors had HLA
      class I or II antibodies and were returned to red cell component donation. Fifty
      seven (6.77%) of the remaining 842 donors were found to have granulocyte-specific
      antibodies of which 11 (1.31%) had HNA-specific antibodies. A total of 818 donors
      (70.70%) were accepted for platelet apheresis, 336 donors (29.04%) were returned
      to red cell component donation, and three donors with HNA-3a antibodies (0.26%)
      were deferred from therapeutic donation. CONCLUSIONS:   Female donors with
      leucocyte antibodies were identified in a stratified screening programme. Donors
      with antibodies were either directed to red cell donation or deferred. This
      process, combined with other measures that have already been introduced, is
      anticipated to further reduce the incidence of TRALI.

PMID- 22150748
TI  - Evidence-based medicine and Cochrane reviews in neonatology: quo vadis?

PMID- 22150749
TI  - Modulation, absorption and delivery of xenobiotics: the synergic role of CYP450
      and P-gp activities.

PMID- 22150750
TI  - Neuroanatomic correlates of psychogenic nonepileptic seizures: a cortical
      thickness and VBM study.
AB  - PURPOSE: Psychogenic nonepileptic seizures (PNES) are among the most common
      clinical manifestations of conversion disorder and consist of paroxysmal behavior
      that resembles epileptic seizures. Preliminary data from functional neuroimaging
      studies gave plausible evidence that limbic circuits and sensorimotor cortex
      might be engaged in conversion disorder. Nonetheless, no advanced magnetic
      resonance imaging (MRI) studies have focused on patients with PNES. METHODS: We
      enrolled 20 consecutive patients in whom the diagnosis of PNES was based on ictal
      video-electroencephalography (EEG) of the habitual episodes and 40 healthy
      subjects matched for age and sex All patients underwent a formal
      neuropsychological investigation and a neuropsychiatric assessment. All of the
      patients also underwent two distinct morphologic whole-brain MR measurements,
      voxel-based morphometry (VBM), and cortical thickness analysis, in a multimethod
      approach. KEY FINDINGS: None of the patients had serious medical or neurologic
      illness, substance abuse, or psychotic disorder, or were taking antipsychotic
      drugs. VBM and cortical thickness analyses in the patients with PNES revealed
      abnormal cortical atrophy of the motor and premotor regions in the right
      hemisphere and the cerebellum bilaterally. We also observed a significant
      association between increasing depression scores and atrophy involving the
      premotor regions. SIGNIFICANCE: The results of this study illustrate that motor
      and premotor regions in the right hemisphere and the cerebellum bilaterally play
      an important role in the pathogenesis of PNES and that these structures are
      correlated with depressive symptoms. Our findings suggest a multistep model in
      the pathogenesis of PNES, in which the phenomenology is driven by psychological
      factors interacting with specific biologic abnormalities.

PMID- 22150751
TI  - Host factors associated with the kinetics of Epstein-Barr virus DNA load in
      patients with primary Epstein-Barr virus infection.
AB  - The aims of this study were to elucidate the kinetics of Epstein-Barr virus (EBV)
      DNA load in serially collected peripheral blood mononuclear cells of patients
      with primary EBV infection, and to determine the correlated host factors. Blood
      samples were collected from 24 patients with primary EBV infection. EBV DNA copy
      numbers were measured using real-time polymerase chain reaction. Based on the
      kinetics of EBV DNA load, the 24 patients were divided into two groups: rapid
      regression and slow regression. Eighteen of the 24 patients (75%) were included
      in the slow regression and 6 (25%) in the rapid regression group. No
      statistically significant differences were observed between the two groups in
      clinical features and laboratory findings. However, acute phase (3 to 10 days
      after the onset of the illness) serum samples from six children in the slow
      regression and four in the rapid regression group revealed significantly higher
      serum interleukin (IL)-1beta (P= 0.018), IL-12 (P= 0.009), tumor necrosis factor
      alpha (P= 0.019), interferon-inducible protein 10, and monokine induced by
      interferon gamma concentrations in the rapid regression than the slow regression
      group. On the other hand, sera from six children in the slow regression and four
      in the rapid regression group in the convalescent phase (14 to 21 days after the
      onset of the illness) showed no statistically significant differences between the
      two groups in these biomarker concentrations. Based on this, it was concluded
      that the kinetics of EBV DNA load can be divided to two different patterns after
      primary EBV infection, and immune response might be associated with viral
      clearance.

PMID- 22150752
TI  - Getting past nature as a guide to the human sex ratio.
AB  - Sex selection of children by pre-conception and post-conception techniques
      remains morally controversial and even illegal in some jurisdictions. Among other
      things, some critics fear that sex selection will distort the sex ratio, making
      opposite-sex relationships more difficult to secure, while other critics worry
      that sex selection will tilt some nations toward military aggression. The human
      sex ratio varies depending on how one estimates it; there is certainly no one-to
      one correspondence between males and females either at birth or across the human
      lifespan. Complications about who qualifies as 'male' and 'female' complicate
      judgments about the ratio even further. Even a judiciously estimated sex ratio
      does not have, however, the kind of normative status that requires society to
      refrain from antenatal sex selection. Some societies exhibit lopsided sex ratios
      as a consequence of social policies and practices, and pragmatic estimates of
      social needs are a better guide to what the sex ratio should be, as against
      looking to 'nature'. The natural sex ratio cannot be a sound moral basis for
      prohibiting parents from selecting the sex of their children, since it ultimately
      lacks any normative meaning for social choices.

PMID- 22150754
TI  - Preoperative ultrasound monitoring can reduce postoperative bladder distension: a
      randomized study.
AB  - OBJECTIVE: The aim of this study was to explore whether close preoperative
      ultrasound monitoring starting in the emergency room (ER) could prevent
      postoperative bladder distension among acute orthopaedic patients. MATERIAL AND
      METHODS: A randomized controlled trial was conducted at a 650-bed level-2 centre
      in Sweden. Inclusion criteria were admittance via ER to an orthopaedic ward for
      acute surgery. Bladder volumes were measured with a portable ultrasound scanner
      (Bladderscan BVI 3000). In the intervention group, all patients were scanned in
      the ER and then regularly at the ward at predefined times until surgery. In the
      control group, no regular scanning was performed before surgery. During surgery,
      the same procedure was performed for both groups: bladder scanning immediately
      after arrival to the recovery room and continuous postoperative scanning until
      voiding. The primary outcome was postoperative bladder distension, defined as a
      bladder volume >=500 ml. Secondary outcomes were postoperative urinary tract
      infection and hospital length of stay. RESULTS: A total of 281 patients completed
      the study, 141 in the intervention group and 140 in the control group.
      Postoperative bladder distension was significantly higher in the control group
      (27.1% vs 17.0%; p = 0.045, 95% confidence interval 4.9-19.8) in the intention-to
      treat, per-protocol and as-treated analyses. No statistical difference was found
      between the intervention group and the control group regarding the secondary
      outcomes. CONCLUSIONS: Frequent bladder monitoring starting in the ER can reduce
      postoperative bladder distension among acute orthopaedic patients. A preoperative
      bladder monitoring protocol should be implemented early in the ER for all
      patients admitted for acute orthopaedic procedures.

PMID- 22150755
TI  - Detection of amitriptyline, citalopram, and metabolites in porcine bones
      following extended outdoor decomposition.
AB  - Skeletal remains of a domestic pig were assessed for relative distribution of
      amitriptyline, citalopram, and metabolites. Following acute exposure and outdoor
      decomposition for 2 years, drugs and metabolites were analyzed in 13 different
      bones. Bones were pulverized following a simple wash procedure, and drugs were
      extracted by passive incubation in methanol, followed by solid-phase extraction.
      Samples were analyzed by ultra-high performance liquid chromatography (UHPLC) and
      confirmed with gas chromatography-mass spectrometry. The Kruskall-Wallis test
      showed that bone type was a main effect with respect to drug level for all
      analytes, with levels varying from 33- to 166-fold. Ratios of levels of drug to
      that of the corresponding metabolite were less variable, varying roughly one- to
      eightfold. This suggests limitations in the interpretive value of drug
      measurements in bone and that relative levels of drug and metabolites should be
      further investigated in terms of forensic value.

PMID- 22150756
TI  - Psychometric properties of three instruments to measure recovery.
AB  - BACKGROUND: The process of recovery is gaining more and more attention within
      health care for patients with severe mental illness. Therefore, instruments to
      measure recovery can be useful for clinical and research purposes. AIMS: This
      study evaluates the psychometric properties of three instruments pertaining to
      recovery for possible application in the Netherlands. The Recovery Attitude
      Questionnaire and the Recovery Knowledge Inventory were investigated among 210
      mental health professionals, and the Recovery Promoting Relationship Scale was
      administered to 142 mental health consumers. METHODS: The factor structure,
      reliability and internal consistency were examined using the same analysis
      strategy. First, each questionnaire was submitted to a confirmatory factor
      analysis based on the factorial structure proposed by the original developers of
      the questionnaire. In case of a bad fit, an exploratory factor analysis was
      conducted. Based on factor analyses, subscales were formed for each questionnaire
      and the internal consistency (Cronbach's alpha) was assessed. In all three cases
      the final principal axes solution was obliquely rotated by means of the OBLIMIN
      rotation procedure. RESULTS: The originally proposed factor structure did not
      yield an acceptable fit in any of the Dutch samples. After analyses, three
      instruments are proposed that are suitable for research on recovery-oriented
      competencies and the recovery-promoting relationship for professionals working
      with people with serious mental illness in the Netherlands. CONCLUSIONS: The
      results in this study may be a step forward and give a new impulse to stimulate
      research in mental health recovery.

PMID- 22150757
TI  - Clinical outcomes, resource use, and costs at 1 year in patients with acute
      coronary syndrome undergoing PCI: results from the multinational APTOR registry.
AB  - BACKGROUND: Limited prospectively collected data are available on the total
      outcomes, cost estimates, and quality of life associated with treatment of acute
      coronary syndrome (ACS) through 1 year in a nonclinical-trial setting, or on the
      impact of new clinical events by 1 year on resource utilization and costs.
      METHODS: The Antiplatelet Therapy Observational Registry (APTOR) 12-month study
      followed 1,335 concurrently recruited ACS patients undergoing percutaneous
      coronary intervention (PCI) and treated with antiplatelet therapy from France,
      Spain, and the United Kingdom in a "real world" clinical setting. Data were
      collected on clinical events, resource utilization, quality of life, and cost
      estimates through 1-year follow-up. RESULTS: By 1 year, 14.4% (95% CI 12.7-16.4%)
      of patients experienced a clinical event of death, MI, stroke, unstable angina,
      urgent target vessel revascularization, or acute heart failure. Costs by 1 year
      were higher among those who had a new clinical event (L8,988, 95% CI L7,848,
      L10,395) as compared with those with no events (L5,809, 95% CI L5,486, L6,161).
      This increased cost was due to higher postdischarge resource use costs. Using the
      EQ-5D assessment at 1 year, quality of life was directionally lower in those
      patients who had experienced a new clinical event. CONCLUSIONS: The risk of
      experiencing a new clinical event during the year following an ACS, which was
      treated with PCI, remains high among European patients, with one-seventh of
      patients having a new event. These additional clinical outcomes reduce quality of
      life and increase health care expenditures, expanding the already high cost of
      treatment for ACS.

PMID- 22150759
TI  - Phylogenetic reference data for systematics and phylotaxonomy of arbuscular
      mycorrhizal fungi from phylum to species level.
AB  - Although the molecular phylogeny, evolution and biodiversity of arbuscular
      mycorrhizal fungi (AMF) are becoming clearer, phylotaxonomically reliable
      sequence data are still limited. To fill this gap, a data set allowing resolution
      and environmental tracing across all taxonomic levels is provided. Two
      overlapping nuclear DNA regions, totalling c. 3 kb, were analysed: the small
      subunit (SSU) rRNA gene (up to 1800 bp) and a fragment spanning c. 250 bp of the
      SSU rDNA, the internal transcribed spacer (ITS) region (c. 475-520 bp) and c. 800
      bp of the large subunit (LSU) rRNA gene. Both DNA regions together could be
      analysed for 35 described species, the SSU rDNA for c. 76 named and 18 as yet
      undefined species, and the ITS region or LSU rDNA, or a combination of both, for
      c. 91 named and 16 as yet undefined species. Present phylogenetic analyses, based
      on the three rDNA markers, provide reliable and robust resolution from phylum to
      species level. Altogether, 109 named species and 27 cultures representing as yet
      undefined species were analysed. This study provides a reference data set for
      molecular systematics and environmental community analyses of AMF, including
      analyses based on deep sequencing.

PMID- 22150761
TI  - Spontaneous coronary artery dissection.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare and potentially deadly
      disease without a clear and universal treatment. Medical as well as mechanical
      interventions, including percutaneous and coronary bypass surgery, have been
      used. We present two dissimilar cases of SCAD that required markedly different
      treatments reflecting the variety in clinical presentation and outcome. A brief
      review of the literature is included.

PMID- 22150762
TI  - Modification of chemokine pathways and immune cell infiltration as a novel
      therapeutic approach in liver inflammation and fibrosis.
AB  - Despite increasing knowledge about molecular pathways in pathogenesis of chronic
      liver disease, selective therapeutic options are scarce, especially in advanced
      diseases characterized by scarring of the liver (termed fibrosis) or even
      complete cirrhosis. Sustained hepatic inflammation as a result to various types
      of injury (e.g., hepatitis C, nonalcoholic steatohepatitis) is generally accepted
      to represent the key prerequisite for fibrogenesis. Liver inflammation is
      characterized by an activation of distinct chemokine pathways in the liver and
      the circulation allowing distinct immune cell populations to enter the liver via
      sinusoids and postsinusoidal venules. Recent investigations have shed light on
      the intimate interactions between the fibrogenic hepatic stellate cell (HSC) and
      infiltrating immune cells, which fundamentally drive liver scarring. Experimental
      fibrosis and inflammation models have demonstrated that disruption of chemokine
      pathways such as CCL2 (MCP-1) or its receptor CCR2, CCL5 (RANTES) or CCR1 / CCR5
      and others may efficiently prevent collagen deposition, by targeting monocytes
      and macrophages, T-cell populations or NKT cells. However, immigration of certain
      mononuclear cells may even be beneficial in the course of fibrosis. Infiltrating
      NK cells and monocyte-derived macrophage subsets can promote resolution of
      extracellular matrix. This emphasizes that hepatic fibrosis is not a
      unidirectional process, but can be reverted up to a certain point. The present
      review aims at summarizing the contribution of immune cell infiltration as well
      as related chemokine systems to experimental liver fibrosis and will discuss
      possible therapeutic applications in humans, with a special emphasis on the
      monocyte/macrophage lineage and their related chemokine pathways.

PMID- 22150760
TI  - Laminin-111 stimulates proliferation of mouse embryonic stem cells through a
      reduction of gap junctional intercellular communication via RhoA-mediated Cx43
      phosphorylation and dissociation of Cx43/ZO-1/drebrin complex.
AB  - Gap junctions within extracellular matrix (ECM)-defined boundaries ensure
      synchronous activity between cells destined to become functional mediators that
      regulate cell behavior. However, the role of ECM in connexin (Cx) function in
      mouse embryonic stem cells (mESCs) has not been elucidated. Therefore, we
      examined the role of laminin-111 in the control of Cx43 functions and related
      signal pathways in mESCs. ECM components (laminin-111, fibronectin, and collagen
      I) increased Cx43 phosphorylation and decreased Lucifer yellow (Ly) diffusion. In
      addition, laminin-111 increased the proliferation index through reduction of gap
      junctional intercellular communication (GJIC), which was confirmed by 18alpha
      glycyrrhetinic acid (18alpha-GA). Laminin-111 increased phosphorylation of focal
      adhesion kinase (FAK)/Src and protein kinase C (PKC), which were inhibited by
      integrin beta1 antibody (Ab) and laminin receptor-1 (LR-1) Ab, respectively. In
      addition, inhibition of both FAK/Src and PKC blocked Cx43 phosphorylation.
      Laminin-111 increased the Ras homolog gene family, member A (RhoA) activation,
      which was blocked by FAK/Src and PKC inhibitors, suggesting the existence of
      parallel pathways that merge at RhoA. Inhibition of RhoA reversed the laminin-111
      induced increase of Cx43 phosphorylation and reduction of GJIC. Laminin-111 also
      stimulated the dissociation of Cx43/ZO-1 complex followed by disruption of
      Cx43/drebrin and Cx43/F-actin complexes, which were reversed by C3 (RhoA
      inhibitor). ZO-1 small interfering (si) RNA significantly decreased Ly diffusion.
      Moreover, laminin-111 decreased Cx43 labeling at the intercellular junction,
      whereas pretreatment with degradation inhibitors (lysosomal protease inhibitor,
      chloroquine; proteasome inhibitor, lactacystin) increased Cx43 expression,
      reversely. In conclusion, laminin-111 stimulated mESC proliferation through a
      reduction of GJIC via RhoA-mediated Cx43 phosphorylation and Cx43/ZO-1/drebrin
      complex instability-mediated Cx43 degradation.

PMID- 22150763
TI  - The evaluation of endothelial functions in patients with celiac disease.
AB  - AIM: Celiac disease is characterized by malabsorption resulting from inflammatory
      injury to the mucosa of the small intestine after the ingestion of wheat gluten
      or related rye and barley proteins. This study aimed to identify individuals who
      are at risk of heart failure and increased risk for cardiovascular events by
      evaluating endothelial function in patients with celiac disease. MATERIALS AND
      METHODS: The study included 36 patients with celiac disease and 35 healthy
      volunteers. After all routine laboratory examination, left ventricular functions
      were evaluated with standard two-dimensional, M-mode conventional Doppler
      methods. Then, flow-mediated dilatation and nitroglycerin-dependent dilatation
      tests on brachial artery were performed to all patients and controls. RESULTS: A
      total of 36 celiac patients and 35 healthy volunteers were included in the study.
      The brachial artery diameter at baseline was similar between both groups.
      Measured brachial artery diameter after hyperemia was 30.19 +/- 4.47 mm in celiac
      patients and 32.35 +/- 3.77 mm in the control group. Differences between two
      groups were statistically significant (P = 0.031). Flow-mediated vasodilatation
      was lower in celiac patients compared with in controls (10.61 +/- 2.64% vs 13.09
      +/- 2.9%; P = 0.0003). Measured endothelium-independent vasodilatation in the
      brachial artery before and after nitroglycerin was similar between both groups (P
      = 0.09 and P = 0.07, respectively). CONCLUSION: This research which aimed to
      evaluate endothelial dysfunction in patients with celiac disease is the first in
      the literature. As a result of this study, we found endothelial dysfunction at
      the macrovascular level in celiac patients.

PMID- 22150764
TI  - Sinus floor elevation using osteotome technique without grafting materials: a 2
      year retrospective study.
AB  - OBJECTIVE: The study aimed to assess the clinical results after osteotome
      technique to lift sinus floor, without graft materials in the residual bone
      height (RBH), below 8 mm. MATERIAL AND METHODS: Twenty-two patients aged from 19
      to 70 years old in need of maxillary sinus floor augmentation were enrolled in
      this study. Preoperative and postoperative cone beam computerized tomography
      (CBCT) were taken to guide the surgery. Twenty-seven implants were inserted and
      followed clinically, another CBCT exam was taken at 6 months postoperatively. The
      diameter of the implants was 4.7 mm (SD 0.4 mm), the length was 10 mm (SD 1.0
      mm). The average residual bone height was 6.7 mm (SD 1.2 mm). RESULTS: No
      implants were lost after the surgery and the 2 years follow-up. There was no
      obvious marginal bone loss during the 6 months follow-up verified by CBCT. The
      mean bone gain at the implant sites was 2.5 mm (SD 1.5 mm). CONCLUSION: The study
      verified the good and stable clinical result of the OSFE technique without using
      bone grafting materials when the RBH was only 4.1-8 mm.

PMID- 22150765
TI  - A pseudo-Bayesian shrinkage approach to regression with missing covariates.
AB  - We consider the linear regression of outcome Y on regressors W and Z with some
      values of W missing, when our main interest is the effect of Z on Y, controlling
      for W. Three common approaches to regression with missing covariates are (i)
      complete-case analysis (CC), which discards the incomplete cases, and (ii)
      ignorable likelihood methods, which base inference on the likelihood based on the
      observed data, assuming the missing data are missing at random (Rubin, 1976b),
      and (iii) nonignorable modeling, which posits a joint distribution of the
      variables and missing data indicators. Another simple practical approach that has
      not received much theoretical attention is to drop the regressor variables
      containing missing values from the regression modeling (DV, for drop variables).
      DV does not lead to bias when either (i) the regression coefficient of W is zero
      or (ii) W and Z are uncorrelated. We propose a pseudo-Bayesian approach for
      regression with missing covariates that compromises between the CC and DV
      estimates, exploiting information in the incomplete cases when the data support
      DV assumptions. We illustrate favorable properties of the method by simulation,
      and apply the proposed method to a liver cancer study. Extension of the method to
      more than one missing covariate is also discussed.

PMID- 22150766
TI  - Lessons from the use of vignettes in the study of mental health service
      disparities.
AB  - OBJECTIVE: To examine the development, feasibility, and use of a vignette
      approach as an important tool in health services disparities research. DATA
      SOURCE: Interviews with vignette developers and qualitative data from a novel
      mental health services disparities study that used vignettes in two samples: (1)
      predominantly low-income parents of children attending mental health specialty
      care who were Latino or non-Latino White and (2) Latino and non-Latino mental
      health clinicians who treat children in their practice. STUDY DESIGN: We conduct
      a content analysis of qualitative data from patients and providers in the Ethnic
      Differences Study to explore the feasibility of vignette methodology in health
      services disparities research, and we identify lessons learned that may guide
      future vignette development. PRINCIPAL FINDINGS: Vignettes provide a valuable
      approach that is acceptable to participants, elicits important insight on
      participant experience and services, and sheds light on factors that can help
      optimize study design for exploring health disparities questions. CONCLUSIONS:
      Researchers, clinicians, and others should consider a set of factors that help
      determine when a vignette approach is warranted in research, training, or for
      other uses, including how best to address identified weaknesses.

PMID- 22150767
TI  - Aquatic Leisure satisfaction and engagement in Neuropalliative Disability
      Management.
AB  - This article describes a single-case design study and uses an occupational
      science focus to explore the effects of 'Aquability' as perceived by participants
      with neuropalliative conditions. Data collection tools include the Individual
      Child Engagement Record and the adapted Leisure Satisfaction Scale--short form by
      14 participants (who had Barthel scores averaging 7/100). The time-sampled
      observations of engagement showed a significant difference between the scores for
      the control condition and the 'Aquability' sessions. The participants reported
      being in control, learning about themselves or others and feeling healthier after
      a session. They reported experiencing a sense of achievement and novelty, which
      was interesting and enjoyable. 'Aquability' appears to be a satisfying use of
      free time for participants with neuropalliative conditions.

PMID- 22150768
TI  - Targeting gaseous molecules to protect against cerebral ischaemic injury:
      mechanisms and prospects.
AB  - 1. Ischaemic brain injury is a leading cause of death and disability in many
      countries. However, the pathological mechanisms underlying ischaemic brain
      injury, including oxidative stress, calcium overload, excitotoxicity and neuronal
      apoptosis, are perplexing and this makes it difficult to find effective novel
      drugs for the treatment of the condition. 2. Recently, gaseous molecules such as
      nitric oxide (NO), carbon monoxide (CO), hydrogen sulphide (H(2)S) and hydrogen
      (H(2)) have attracted considerable interest because of their physiological and
      pathophysiological roles in various body systems. Emerging evidence indicates
      that gaseous molecules are involved in the pathological processes of ischaemic
      brain damage. 3. In the present review, we summarize evidence regarding the
      involvement of gaseous molecules in ischaemic brain injury and discuss the
      therapeutic potential of targeting gaseous molecules. 4. Collectively, the
      available data suggest that the application of these biological gas molecules and
      their pharmacological regulators may be a potential therapeutic approach for the
      treatment of ischaemic brain injury.

PMID- 22150769
TI  - Synopsis of Equine Veterinary Journal Supplement 37: Equine Ophthalmology III
      'Reviews in memory of Keith Barnett'. Part 2.

PMID- 22150770
TI  - Algorithm for lamotrigine dose adjustment before, during, and after pregnancy.
AB  - BACKGROUND: Treatment with lamotrigine (LTG) during pregnancy is associated with
      a pronounced risk of seizure deterioration, because pregnancy accelerates LTG
      elimination. The extent to which pregnancy affects LTG pharmacokinetics is
      unpredictable and varies considerably among patients. AIM: We propose an
      algorithm for systematic LTG plasma concentration monitoring and dose adjustment
      to guide the clinician between the risk of seizure deterioration and LTG toxicity
      by maintaining a stable LTG concentration, using the optimal prepregnancy target
      concentration as a reference. METHODS: The reference LTG plasma concentration
      (RC) should be determined before pregnancy or as early in pregnancy as possible.
      After conception, plasma concentration of LTG should be measured every 4 weeks
      throughout pregnancy. When the LTG plasma concentration falls below the RC, the
      dose of LTG should be increased by 20-25%. Post-partum, the plasma concentration
      of LTG should be measured within the first or second week, and if the LTG plasma
      concentration is higher than the RC, the LTG dose should be reduced by 20-25% and
      the procedure repeated until RC is re-established. CONCLUSIONS: Seizure
      deterioration during pregnancy may be prevented or reduced by closely and
      systematically following our proposed algorithm.

PMID- 22150771
TI  - Modelling photosynthetic responses to temperature of grapevine (Vitis vinifera
      cv. Semillon) leaves on vines grown in a hot climate.
AB  - Field measurements of photosynthesis of Vitis vinifera cv. Semillon leaves in
      relation to a hot climate, and responses to photon flux densities (PFDs) and
      internal CO(2) concentrations (c(i) ) at leaf temperatures from 20 to 40  degrees
      C were undertaken. Average rates of photosynthesis measured in situ decreased
      with increasing temperature and were 60% inhibited at 45  degrees C compared with
      25  degrees C. This reduction in photosynthesis was attributed to 15-30% stomatal
      closure. Light response curves at different temperatures revealed light-saturated
      photosynthesis optimal at 30  degrees C but also PFDs saturating photosynthesis
      increased from 550 to 1200 umol (photons) m(-2)s(-1) as temperatures increased.
      Photosynthesis under saturating CO(2) concentrations was optimal at 36  degrees C
      while maximum rates of ribulose 1,5-bisphosphate (RuBP) carboxylation (V(cmax))
      and potential maximum electron transport rates (J(max)) were also optimal at 39
      and 36  degrees C, respectively. Furthermore, the high temperature-induced
      reduction in photosynthesis at ambient CO(2) was largely eliminated. The
      chloroplast CO(2) concentration at the transition from RuBP regeneration to RuBP
      carboxylation-limited assimilation increased steeply with an increase in leaf
      temperature. Semillon assimilation in situ was limited by RuBP regeneration below
      30  degrees C and above limited by RuBP carboxylation, suggesting high
      temperatures are detrimental to carbon fixation in this species.

PMID- 22150772
TI  - The ethics of sham surgery in Parkinson's disease: back to the future?
AB  - Despite intense academic debate in the recent past over the use of 'sham surgery'
      control groups in research, there has been a recent resurgence in their use in
      the field of neurodegenerative disease. Yet the primacy of ethical arguments in
      favour of sham surgery controls is not yet established. Preliminary empirical
      research shows an asymmetry between the views of neurosurgical researchers and
      patients on the subject, while different ethical guidelines and regulations
      support conflicting interpretations. Research ethics committees faced with a
      proposal involving sham surgery should be aware of its ethical complexities. An
      overview of recent and current placebo-controlled surgical trials in the field of
      Parkinson's Disease is provided here, followed by an analysis of the key ethical
      issues which such trials raise.

PMID- 22150773
TI  - Disrobing associated with epileptic seizures and forensic implications.
AB  - Little is known about the clinical aspects and medico-legal consequences of
      disrobing in the context of epileptic seizures. Seizure-related disrobing may
      occur either as an ictal automatism or during the postictal period. Some patients
      may experience a seizure while already in the unclothed state, engage in ictal
      wandering, and thereby appear in public in the nude. Two cases involving
      disrobing associated with seizures captured via video-monitored
      electroencephalography are offered. An additional case reveals the legal
      consequences endured by one patient who experienced a nocturnal seizure and began
      wandering in an unclothed state. Collectively, these cases illustrate the medical
      reality of seizure-related disrobing and the related adverse effects on patients'
      quality of life. Disrobing associated with epileptic seizures carries the
      potential for serious legal consequences if not properly identified as an ictal
      phenomenon.

PMID- 22150774
TI  - Corneal parameters of six- to 12-year-old Chinese children.
AB  - PURPOSE: The aim was to determine the corneal parameters in low to moderate
      myopic Chinese children and to investigate the differences in these corneal
      parameters between male and female subjects. METHODS: Refractive errors and
      corneal parameters were retrieved from subjects who had participated in studies
      on myopia and astigmatism in 2008 and 2009. Corneal parameters including
      simulated K (Sim K) and asphericity (Q) at 9.0 mm chord and horizontal visible
      iris diameter (HVID) were determined for 217 children (112 males and 105 females
      aged from six to 12 years) using the Medmont E300 topographer. RESULTS: The Q of
      the corneas was -0.44 +/- 0.12 along the flat meridian and -0.22 (-0.70 to 0.63)
      along the steep meridian. The HVID and Sim K of male subjects were larger and
      flatter than female subjects. The mean HVID of male and female subjects was 11.3
      +/- 0.3 mm and 11.1 +/- 0.30 mm, respectively. The mean Sim K value in male and
      female subjects was 7.91 +/- 0.24 mm and 7.79 +/- 0.21 mm, respectively, along
      the flat meridian, and was 7.65 +/- 0.26 mm and 7.53 +/- 0.24 mm, respectively,
      along the steep meridian. CONCLUSIONS: All corneas were prolate elliptical in
      shape along the flat meridian and the peripheral flattening rate was found to be
      greater along the flat meridian. A greater flattening rate was observed in the
      corneas of Chinese children when compared to that of Caucasian children. The Q
      between male and female subjects was not significantly different. Male subjects
      tended to have larger HVID and flatter corneas than female subjects.

PMID- 22150775
TI  - Minimum qualifications in the alcohol and other drugs field: employers' views.
AB  - INTRODUCTION AND AIMS: To examine employers' opinions of minimum qualifications
      and perceptions of vocational education and training (VET) and determine the
      extent to which the VET sector addressed current workforce development needs in
      the alcohol and other drugs (AOD) field. DESIGN AND METHODS: An online survey of
      186 AOD treatment agency managers across Australia was conducted to determine
      levels of satisfaction with and attitudes toward AOD VET qualifications as a
      minimum qualification. Descriptive analyses were undertaken. RESULTS: Most
      managers were supportive of a minimum qualification strategy and deemed VET AOD
      qualifications sufficient as a minimum level qualification. However, over half
      indicated that the minimum qualification should be higher than certificate IV
      level. One in four managers were dissatisfied with VET provided by technical and
      further education colleges. When seeking to employ AOD specialist workers, most
      managers preferred those with university level qualifications rather than VET
      qualifications. DISCUSSION AND CONCLUSIONS: VET has potential to meet the
      increasingly complex needs of AOD work by providing ongoing certificate and
      diploma level training and qualifications at the vocational graduate level.
      However, the relatively high levels of dissatisfaction with the VET sector, and
      concern regarding the ability of certificate IV level training to meet the needs
      of the AOD workforce, warrant attention. Improved linkages and relationships
      between the AOD field and the VET sector could increase the quality of training
      provided and may assist in addressing the AOD workforce development needs.

PMID- 22150776
TI  - Staphylococcus lugdunensis native mitral valve endocarditis after liver
      transplantation.

PMID- 22150777
TI  - Ethanol affects differentiation-related pathways and suppresses Wnt signaling
      protein expression in human neural stem cells.
AB  - BACKGROUND: Prenatal exposure of the fetus to ethanol (EtOH) can be teratogenic.
      We previously showed that EtOH alters the cell fate of human neural stem cells
      (NSC). As Wnt signaling plays an important role in fetal brain development, we
      hypothesized that EtOH suppresses Wnt signaling protein expression in
      differentiating NSC and thereby contributes to fetal alcohol spectrum disorder.
      METHODS: NSC isolated from fetal human brains were cultured in mitogenic media to
      induce neurospheres, which were dissociated into single-cell suspensions and used
      for all experiments. Equal numbers of NSC were cultured on lysine/laminin-coated
      plates for 96 hours in differentiating media containing 0, 20, or 100 mM EtOH.
      Total mRNA was isolated from samples containing 0 or 100 mM EtOH and changes in
      expression of 263 genes associated with neurogenesis and NSC differentiation were
      determined by Oligo GEArray technology. The biological impact of gene changes was
      estimated using a systems biology approach with pathway express software and KEGG
      database. Based on the pathways identified, expression of Wnt proteins (Wnt3a and
      Wnt5a), Wnt-receptor complex proteins (p-LRP6, LRP6, DVL2, and DVL3), Wnt
      antagonist Naked-2 (NKD-2), and downstream Wnt proteins (beta-catenin, Tyr-p
      GSK3beta, Ser-p-GSK3beta) were analyzed by Western blot. RESULTS: Of the 263
      genes examined, the expressions of 22 genes in differentiating NSC were either
      upwardly or downwardly affected by EtOH. These genes are associated with 5
      pathways/cellular processes: axon guidance; hedgehog signaling; TGF-beta
      signaling; cell adhesion molecules; and Wnt signaling. When compared to controls,
      EtOH, at both 20 and 100 mM concentrations, suppressed the expression of Wnt3a
      and Wnt5a, receptor complex proteins p-LRP6, LRP6 and DVL2, and cytoplasmic
      proteins Ser-p-GSK3beta and beta-catenin. Expression of NKD-2 and DVL3 remained
      unchanged and the expression of active Tyr-p-GSK3beta increased significantly.
      CONCLUSIONS: EtOH can significantly alter neural differentiation pathway-related
      gene expression and suppress Wnt signaling proteins in differentiating human NSC.

PMID- 22150778
TI  - Inter-laboratory comparison of different rapid methods for the detection of
      bacterial contamination in platelet concentrates.
AB  - BACKGROUND:   Bacterial contamination of platelet concentrates still represents a
      major risk in transfusion medicine, and a variety of screening methods have been
      available to improve the safety of PCs. In the present study, the analytical
      quality of three different rapid screening methods (BactiFlow flow cytometry, Pan
      Genera Detection Assay, 23S rRNA RT-PCR) was evaluated in an inter-laboratory
      comparison in three different German blood services. METHODS:   Samples were
      inoculated with different bacteria [Staphylococcus aureus, Staphylococcus
      epidermidis, Escherichia coli (two strains), Klebsiella pneumoniae (two strains),
      Enterobacter aerogenes (one strain), Serratia marcescens (one strain)] at
      different counts (4.5 * 10(3) -4.5 * 10(8)  CFU/ml) alternating with negative
      samples in one transfusion facility. Samples were blinded with a random order for
      each screening method, shipped to partners and analysed immediately after receipt
      with different rapid screening methods. RESULTS:   The inter-laboratory
      comparison revealed that the BactiFlow assay and 23S rRNA RT-PCR-screening
      detected all samples correctly (positive: 12/12, negative: 8/8). The Pan Genera
      Detection Assay test detected only four of the positive samples. Four of the non
      detected positive samples were below the assay's detection limit. Another four
      inoculated samples with comparatively high bacteria counts were detected false
      negative (E. coli (two strains): 9.87 * 10(5) and 2.10 * 10(7)  CFU/ml,
      respectively, K. pneumoniae: 4.79 * 10(6)  CFU/ml, S. aureus: 6.03 * 10(5) 
      CFU/ml). All rapid screening methods revealed no false-positive results.
      CONCLUSIONS:   Both BactiFlow and 23S rRNA RT-PCR demonstrated a high sensitivity
      to detecting bacterial contamination in PCs. The Pan Genera Detection Assay had
      some shortcomings regarding sensitivity, especially for the detection of Gram
      negative strains.

PMID- 22150780
TI  - Successful non-surgical treatment of perirenal haematoma after percutaneous renal
      artery angioplasty in a solitary kidney.
AB  - Renal artery angioplasty with stent placement represents an effective choice for
      correcting renal artery stenosis. However, if iatrogenic renal artery injury
      occurs, as in the case of solitary kidney, the risk of requiring chronic dialysis
      increases. This article reports the case of a patient with a solitary kidney, who
      underwent renal stenting and developed a retroperitoneal haematoma. The patient
      was managed conservatively and the perirenal haematoma resolved. Within the
      period of follow-up, the patient had maintained stable renal function with
      adequate blood pressure control.

PMID- 22150779
TI  - Low frequency stimulation of ventral hippocampal commissures reduces seizures in
      a rat model of chronic temporal lobe epilepsy.
AB  - PURPOSE: To investigate the effects of low frequency stimulation (LFS) of a fiber
      tract for the suppression of spontaneous seizures in a rat model of human
      temporal lobe epilepsy. METHODS: Stimulation electrodes were implanted into the
      ventral hippocampal commissure (VHC) in a rat post-status epilepticus (SE) model
      of human temporal lobe epilepsy (n = 7). Two recording electrodes were placed in
      the CA3 regions bilaterally and neural data were recorded for a minimum of 6
      weeks. LFS (60 min train of 1 Hz biphasic square wave pulses, each 0.1 ms in
      duration and 200 MUA in amplitude, followed by 15 min of rest) was applied to the
      VHC for 2 weeks, 24 h a day. KEY FINDINGS: The baseline mean seizure frequency of
      the study animals was 3.7 seizures per day. The seizures were significantly
      reduced by the application of LFS in every animal (n = 7). By the end of the 2
      week period of stimulation, there was a significant, 90% (<1 seizure/day)
      reduction of seizure frequencies (p < 0.05) and a 57% reduction during the period
      following LFS (p < 0.05) when compared to baseline. LFS also resulted in a
      significant reduction of hippocampal interictal spike frequency (71%, p < 0.05),
      during 2 weeks of LFS session. The hippocampal histologic analysis showed no
      significant difference between rats that received LFS and SE induction and those
      that had received only SE-induction. None of the animals showed any symptomatic
      hemorrhage, infection, or complication. SIGNIFICANCE: Low frequency stimulation
      applied at a frequency of 1 Hz significantly reduced both the excitability of the
      neural tissue as well as the seizure frequency in a rat model of human temporal
      lobe epilepsy. The results support the hypothesis that LFS of fiber tracts can be
      an effective method for the suppression of spontaneous seizures in a temporal
      lobe model of epilepsy in rats and could lead to the development of a new
      therapeutic modality for human patients with temporal lobe epilepsy.

PMID- 22150781
TI  - Novel flavonoids with antioxidant activity from a Chenopodiaceous plant.
AB  - OBJECTIVE: Atriplex lentiformis (Torr.) S.Wats (Chenopodiaceae) is a wild plant
      which is in use by Bedouin in treatment of general fatigue, therefore, there is a
      need to explore the potential antioxidant activity of the extracts and isolated
      compounds of this plant. METHODS: Column chromatography and spectroscopic
      analysis were used for isolation and identification of the compounds. The
      antioxidant activity was evaluated in vitro using the ABTS(*+) (2,2'-azino-bis-3
      ethyl-bezthiazoine-6-sulphuric acid) radical scavenging model. Liver and kidney
      functions were investigated after oral administration of total alcohol,
      successive extracts, and isolated compounds. RESULTS: Two new flavonoids,
      quercetin-6,4'-dimethoxy-3-fructo-rhamnoside 1 and quercetin-4'-methoxy-3-fructo
      rhamnoside 2 in addition to five known compounds (kaempferol-4'-methoxy-3
      rutinoside 3, kaempferol-7-O-rhamnoside 4, kaempferol-3,7-O,O-dirhamnoside 5,
      quercetin 6, and kaempferol 7) were isolated. Oral administration of total
      ethanol, diethyl ether, chloroform, ethyl acetate and n-butanol extracts showed
      no signs of toxicity up to (5 g/kg. b.wt.). All extracts and isolated compounds
      showed varied antioxidant activity ranged from 129 to 952 umol Trolox
      equivalent/gram dry weight with maximum level for the two new isolated flavonoids
      (985 and 895 umol Trolox equivalent/gram dry weight). Animals received both total
      ethanol and n-butanol extracts showed a significant increase in ALT, AST, blood
      urea, and serum creatinine levels.

PMID- 22150782
TI  - Patient perceptions of an art-making experience in an outpatient blood and marrow
      transplant clinic.
AB  - This study explored blood and marrow transplantation (BMT) patients' perceptions
      of an art-making experience during BMT treatment. Participants including patients
      receiving BMT for a variety of cancers (10 men/10 women, aged 20-68) were offered
      a 1 hour tile-painting activity during treatment. Participants with cognitive
      impairment and respiratory precautions were excluded from the study. Researchers
      followed immune precaution protocols for the safety of participants. Data were
      collected through semi-structured, in-depth interviews with 20 participants to
      gather information about their perceptions of the art-making experience in a BMT
      clinic setting. Interview recordings were transcribed verbatim and analysed.
      Researchers coded transcripts independently and discussed outcomes together to
      achieve agreement on themes. Twelve themes emerged from the data, with the three
      most prevalent themes being Occupying Time (20.5%), Creative Expression (13.5%),
      and Reactions to Tile Painting (13.5%). Other themes included Support (12.2%),
      Side Effects (7.3%), Other Activities Suggested by Patients (7%), BMT Treatment
      Process (6.2%), Shared Painting Experience (5.9%), Life Outlook (5.2%), BMT Life
      Changes (3.8%), Spirituality (3%) and Barriers (1.9%). Through analysis of these
      themes, researchers have identified this art-making experience as a diversional
      or meaningful way to spend time during treatment, a medium for creative
      expression, and a distraction from negative side effects of the BMT process.

PMID- 22150784
TI  - Rare pits, large vessels and extreme vulnerability to cavitation in a ring-porous
      tree species.
AB  - * The rare pit hypothesis predicts that the extensive inter-vessel pitting in
      large early-wood vessels of ring-porous trees should render many of these vessels
      extremely vulnerable to cavitation by air-seeding. This prediction was tested in
      Quercus gambelii. * Cavitation was assessed from native hydraulic conductivity at
      field sap tension and in dehydrated branches. Single-vessel air injections gave
      air-seeding pressures through vessel files; these data were used to estimate air
      seeding pressures for inter-vessel walls and pits. * Extensive cavitation
      occurred at xylem sap tensions below 1 MPa. Refilling occurred below 0.5 MPa and
      was inhibited by phloem girdling. Remaining vessels cavitated over a wide range
      to above 4 MPa. Similarly, 40% of injected vessel files air-seeded below 1.0 MPa,
      whereas the remainder seeded over a wide range exceeding 5 MPa. Inter-vessel
      walls averaged 1.02 MPa air-seeding pressure, similar and opposite to the mean
      cavitation tension of 1.22 MPa. Consistent with the rare pit hypothesis, only 7%
      of inter-vessel pits were estimated to air-seed by 1.22 MPa. * The results
      confirm the rare pit prediction that a significant fraction of large vessels in
      Q. gambelii experience high probability of failure by air-seeding.

PMID- 22150785
TI  - Anatomical structures in the maxillary sinus related to lateral sinus elevation:
      a cone beam computed tomographic analysis.
AB  - OBJECTIVES: The objective of this study is to evaluate the anatomical structures
      in the maxillary sinus with relation to lateral approach sinus elevation
      utilizing cone beam computed tomography (CT) scans taken prior to sinus elevation
      surgery. MATERIALS AND METHODS: A total of 150 CT images were acquired from 150
      patients (90 men and 60 women; mean age, 49.4 years, range 23-86 years) who were
      being treated with implant-supported restorations in the posterior edentulous
      maxilla. Of the 150 CT scans, 65 were of the right sinus and 85 of the left
      sinus. Measurements of the anatomical structures in the maxillary sinus were
      conducted on the CT images. RESULTS: In the mean width of the lateral wall, there
      were statistically significant values among the measurement points (P < 0.05).
      The anterior area of the sinus lateral wall was thicker than the posterior
      lateral wall. There was a statistically significant difference between the vessel
      diameter and lateral wall width (P < 0.05). As sinus lateral wall width
      increased, so did the vessel diameter. The mean distance to the inferior border
      of the vessel from the sinus floor and from the alveolar crest was 8.25 and 17.03
      mm, respectively. The intraosseous group among the vessel position was 64.3%, so
      the intraosseous vessel could be visualized in CT scans at 64.3%. In angle A, the
      group of less than 30 degrees  was 4.8%. Schneiderian membrane perforation by
      narrow angle had a low risk. The prevalence of the septa related to Schneiderian
      membrane perforation was 44%. The distance to the inferior border of the vessel
      from the alveolar crest being less than 15 mm was 31%. The vessel diameter
      greater than 1 mm was 37.8%. CONCLUSIONS: Based on present research about
      utilizing cone beam CT scans for sinus elevation, the alteration of the lateral
      approach sinus elevation technique is highly recommended if complications such as
      membrane perforation or bleeding are expected.

PMID- 22150787
TI  - Bayesian semiparametric nonlinear mixed-effects joint models for data with
      skewness, missing responses, and measurement errors in covariates.
AB  - It is a common practice to analyze complex longitudinal data using semiparametric
      nonlinear mixed-effects (SNLME) models with a normal distribution. Normality
      assumption of model errors may unrealistically obscure important features of
      subject variations. To partially explain between- and within-subject variations,
      covariates are usually introduced in such models, but some covariates may often
      be measured with substantial errors. Moreover, the responses may be missing and
      the missingness may be nonignorable. Inferential procedures can be complicated
      dramatically when data with skewness, missing values, and measurement error are
      observed. In the literature, there has been considerable interest in
      accommodating either skewness, incompleteness or covariate measurement error in
      such models, but there has been relatively little study concerning all three
      features simultaneously. In this article, our objective is to address the
      simultaneous impact of skewness, missingness, and covariate measurement error by
      jointly modeling the response and covariate processes based on a flexible
      Bayesian SNLME model. The method is illustrated using a real AIDS data set to
      compare potential models with various scenarios and different distribution
      specifications.

PMID- 22150786
TI  - Improved health status with insulin degludec compared with insulin glargine in
      people with type 1 diabetes.
AB  - AIMS: The efficacy and safety of insulin degludec (degludec), a new-generation
      ultra-long-acting basal insulin, was compared with insulin glargine (glargine) in
      people with Type 1 diabetes mellitus in a 16-week, open-label, randomized trial.
      Health status, an important aspect of effective diabetes management, was also
      assessed. METHODS: Degludec (n = 59) or glargine (n = 59) were injected once
      daily, with insulin aspart at mealtimes. Health status assessment utilized the
      validated Short Form 36 Health Survey, version 2, which has two summary component
      scores for mental and physical well-being, each comprising four domains. RESULTS:
      At study end, HbA(1c) reductions were comparable between groups, but confirmed
      nocturnal hypoglycaemia was significantly less frequent with degludec [relative
      rate 0.42 (95% CI 0.25-0.69)], and overall hypoglycaemia numerically less
      frequent [relative rate 0.72 (95% CI 0.52-1.00)]. After 16 weeks, a significant
      improvement in Short Form 36 Health Survey mental component score of +3.01 (95%
      CI 0.32-5.70) was obtained for degludec against glargine, attributable to
      significant differences in the social functioning [+8.04 (95% CI 1.89-14.18)] and
      mental health domains [+2.46 (95% CI 0.10-4.82)]. For mental component score,
      Cohen's effect size was 0.42, indicating a small-to-medium clinically meaningful
      difference. The physical component score [+0.66 (95% CI -2.30 to 3.62)] and
      remaining domains were not significantly different between degludec and glargine.
      CONCLUSIONS: In the context of comparable overall glycaemic control with
      glargine, degludec improved mental well-being as measured using the mental
      component score of the Short Form 36 Health Survey. The improvements in overall
      mental component score and the underlying social functioning and mental health
      domains with degludec compared with glargine may relate to the observed reduction
      in hypoglycaemic events.

PMID- 22150788
TI  - Thai youth bar patrons and harmful alcohol consumption: an underrecognised public
      health issue.

PMID- 22150789
TI  - Is patient safety improving? National trends in patient safety indicators: 1998
      2007.
AB  - CONTEXT: Emphasis has been placed on quality and patient safety in medicine;
      however, little is known about whether quality over time has actually improved in
      areas such as patient safety indicators (PSIs). OBJECTIVE: To determine whether
      national trends for hospital PSIs have improved from 1998 to 2007. DESIGN,
      SETTING, AND PARTICIPANTS: Using PSI criteria from the Agency for Healthcare
      Research and Quality, PSIs were identified in the Nationwide Inpatient Sample
      (NIS) for all eligible inpatient admissions between 1998 and 2007. Joinpoint
      regression was used to estimate annual percentage changes (APCs) for PSIs. MAIN
      OUTCOME MEASURE: Annual percent change for PSIs. RESULTS: From 1998 to 2007, 7.6
      million PSI events occurred for over 69 million hospitalizations. A total of 14
      PSIs showed statistically significant trends. Seven PSIs had increasing APC:
      postoperative pulmonary embolism or deep vein thrombosis (8.94), postoperative
      physiological or metabolic derangement (7.67), postoperative sepsis (7.17),
      selected infections due to medical care (4.05), decubitus ulcer (3.05),
      accidental puncture or laceration (2.64), and postoperative respiratory failure
      (1.46). Seven PSIs showed decreasing APCs: birth trauma injury to neonate (
      17.79), failure to rescue (-6.05), postoperative hip fracture (-5.86), obstetric
      trauma-vaginal without instrument (-5.69), obstetric trauma-vaginal with
      instrument (-4.11), iatrogenic pneumothorax (-2.5), and postoperative wound
      dehiscence (-1.8). CONCLUSION: This is the first study to establish national
      trends of PSIs during the past decade indicating areas for potential quality
      improvement prioritization. While many factors influence these trends, the
      results indicate opportunities for either emulation or elimination of current
      patient safety trends.

PMID- 22150790
TI  - beta-1,3-Glucan given orally modulates immunomyelopoietic activity and enhances
      the resistance of tumour-bearing mice.
AB  - beta-Glucans have been reported to be potent adjuvants in stimulating innate and
      adaptive immune responses. The aim of the present study was to determine the
      immunohematopoietic effects of Imunoglucan (HEBRON) following its oral
      administration to normal and Ehrlich ascites tumour (EAT)-bearing mice. Mice were
      treated with 250, 500 and 1000 mg/kg per day, p.o., Imunoglucan (beta-1,3-glucan
      extracted from Saccharomyces cerevisae) for 18 consecutive days. Treatment
      started 10 days prior to and ended 8 days after tumour inoculation. At 500 and
      1000 mg/kg per day, Imunoglucan enhanced the life span of EAT-bearing mice and
      prevented myelosuppression and splenomegaly caused by the tumour by increasing
      the number of granulocyte-macrophage progenitors in the bone marrow and
      increasing colony-stimulating activity in the serum. At 500 mg/kg, Imunoglucan
      restored the reduced ability of stromal cells to display myeloid progenitors in
      long-term bone marrow cultures of EAT-bearing mice and upregulated the production
      of interleukin (IL)-6 and IL-1alpha by these cells, consistent with a higher
      number of non-adherent cells. Moreover, 500 mg/kg Imunoglucan restored natural
      killer cell activity in tumour-bearing mice, consistent with the increased
      production of interferon (IFN)-gamma observed. The results of the present study
      suggest that Imunoglucan given orally indirectly modulates immune activity and
      probably disengages tumour-induced suppression by producing a higher reserve of
      myeloid progenitors in the bone marrow in consequence of biologically active
      cytokine release (colony-stimulating factors, IL-1alpha, IL-6 and IFN-gamma).

PMID- 22150791
TI  - Universality of phloem transport in seed plants.
AB  - Since Munch in the 1920s proposed that sugar transport in the phloem vascular
      system is driven by osmotic pressure gradients, his hypothesis has been strongly
      supported by evidence from herbaceous angiosperms. Experimental constraints made
      it difficult to test this proposal in large trees, where the distance between
      source and sink might prove incompatible with the hypothesis. Recently, the
      theoretical optimization of the Munch mechanism was shown to lead to surprisingly
      simple predictions for the dimensions of the phloem sieve elements in relation to
      that of fast growing angiosperms. These results can be obtained in a very
      transparent way using a simple coupled resistor model. To test the universality
      of the Munch mechanism, we compiled anatomical data for 32 angiosperm and 38
      gymnosperm trees with heights spanning 0.1-50 m. The species studied showed a
      remarkable correlation with the scaling predictions. The compiled data allowed
      calculating stem sieve element conductivity and predicting phloem sap flow
      velocity. The central finding of this work is that all vascular plants seem to
      have evolved efficient osmotic pumping units, despite their huge disparity in
      size and morphology. This contribution extends the physical understanding of
      phloem transport, and will facilitate detailed comparison between theory and
      field experiments.

PMID- 22150792
TI  - Linking international research to global health equity: the limited contribution
      of bioethics.
AB  - Health research has been identified as a vehicle for advancing global justice in
      health. However, in bioethics, issues of global justice are mainly discussed
      within an ongoing debate on the conditions under which international clinical
      research is permissible. As a result, current ethical guidance predominantly
      links one type of international research (biomedical) to advancing one aspect of
      health equity (access to new treatments). International guidelines largely fail
      to connect international research to promoting broader aspects of health equity -
      namely, healthier social environments and stronger health systems. Bioethical
      frameworks such as the human development approach do consider how international
      clinical research is connected to the social determinants of health but, again,
      do so to address the question of when international clinical research is
      permissible. It is suggested that the narrow focus of this debate is shaped by
      high-income countries' economic strategies. The article further argues that the
      debate's focus obscures a stronger imperative to consider how other types of
      international research might advance justice in global health. Bioethics should
      consider the need for non-clinical health research and its contribution to
      advancing global justice.

PMID- 22150793
TI  - From the uterine cavity to anthropometry.

PMID- 22150794
TI  - The effect of intralesional injection of bone marrow derived mesenchymal stem
      cells and bone marrow supernatant on collagen fibril size in a surgical model of
      equine superficial digital flexor tendonitis.
AB  - REASONS FOR PERFORMING STUDY: Collagen fibril size is decreased in repair tissue
      following tendon injury compared to normal tendon matrix in horses. Mesenchymal
      stem cells have been suggested to promote regeneration of tendon matrix rather
      than fibrotic repair following injury, although this concept remains unproven.
      OBJECTIVES: To explore the hypothesis that implantation of autologous mesenchymal
      stem cells derived from bone marrow into a surgically created central core defect
      in the superficial digital flexor tendon (SDFT) of horses would induce the
      formation of a matrix with greater ultrastructural similarities to tendon matrix
      than the fibrotic scar tissue formed in control defects. METHODS: Tissue was
      collected 16 weeks after induction of injury and 12 weeks after treatment from
      normal and injured regions of control and treated limbs of 6 horses and examined
      using transmission electron microscopy. Collagen fibril diameters were measured
      manually with image analysis software and surface areas calculated. Three
      parameters assessed for normal and injured tissue were mass average diameter
      (MAD), collagen fibril index (CFI) and the area dependent diameter (ADD).
      RESULTS: Normal regions from both treated and control limbs displayed higher MAD
      and CFI values, as well as a characteristic bimodal distribution in fibril size.
      Injured regions from both treated and control limbs displayed significantly lower
      MAD and CFI values, as well as a unimodal distribution in fibril size. There were
      no significant differences between treated and control limbs for any of the
      parameters assessed. CONCLUSIONS: Intralesional injection of autologous bone
      marrow derived mesenchymal stem cells had no measurable effect on the fibril
      diameter of collagen in healing tissue in the SDFT of this experimental model 16
      weeks after injury. POTENTIAL RELEVANCE: Favouring matrix regeneration over
      fibrotic repair may not be the mechanism by which autologous mesenchymal stem
      cells assist healing of tendon injury.

PMID- 22150795
TI  - Residents' perspectives on urinary incontinence: a review of literature.
AB  - BACKGROUND: Individuals in residential aged care facilities experience urinary
      incontinence more than any other single population. Despite these factors, the
      impact of the condition on their quality of life, their perspectives of living
      with the condition, and their preferences for care have received little research
      attention. AIM: To provide a descriptive overview of research about; the impact
      of urinary incontinence on residents' quality of life; residents' perspectives of
      having urinary incontinence; and their preferences for continence care'. DESIGN:
      A descriptive review of literature. METHOD: A broad search was undertaken for
      qualitative and quantitative research that evaluated residents' quality of life
      related to urinary incontinence; their perspectives on having urinary
      incontinence, and their preferences for managing it. Data were displayed in
      tabular format, summarized, and described. RESULTS: Ten studies were identified
      and reviewed (six qualitative and four quantitative). They reveal many residents'
      value having independent bowel and bladder function, but believe that
      incontinence in inevitable and intractable. Some adopt self management
      strategies, however considerable barriers hinder their ability to maintain
      continence and manage incontinence. Residents often have low expectations, and
      hence decline further evaluation and treatment. Some express satisfaction with
      continence care even if this care is not consistent with their preferences.
      Little is known about how cognitively impaired residents perceive their
      condition. However some individuals with cognitive impairment respond with acute
      anxiety when carers' attempt to provide continence care. CONCLUSION: Residents'
      perspectives on incontinence and preferences for continence care relate to low
      expectations for improvement. Such misconceptions should be addressed and
      residents and their family members should be given a range of options from which
      to choose. As urinary incontinence impacts on residents' quality of life, it is
      also important that continence care is delivered in a participative and sensitive
      way.

PMID- 22150796
TI  - Natural selection. III. Selection versus transmission and the levels of
      selection.
AB  - George Williams defined an evolutionary unit as hereditary information for which
      the selection bias between competing units dominates the informational decay
      caused by imperfect transmission. In this article, I extend Williams' approach to
      show that the ratio of selection bias to transmission bias provides a unifying
      framework for diverse biological problems. Specific examples include Haldane and
      Lande's mutation-selection balance, Eigen's error threshold and quasispecies, Van
      Valen's clade selection, Price's multilevel formulation of group selection,
      Szathmary and Demeter's evolutionary origin of primitive cells, Levin and Bull's
      short-sighted evolution of HIV virulence, Frank's timescale analysis of microbial
      metabolism and Maynard Smith and Szathmary's major transitions in evolution. The
      insights from these diverse applications lead to a deeper understanding of kin
      selection, group selection, multilevel evolutionary analysis and the
      philosophical problems of evolutionary units and individuality.

PMID- 22150797
TI  - Understanding risks of workplace injury in labor and delivery.
AB  - OBJECTIVES: To understand nurse and other staff perceptions about care activities
      in labor and delivery (L&D) that were performed with high frequency, required
      high exertion, and had the greatest potential to cause injury and to determine
      what personal characteristics might be related to the caregiving tasks with
      potential for injury. DESIGN: This exploratory study employed a mixed methods
      design using qualitative open-ended questions and quantitative surveys
      administered in three different times (n = 56, 58, and 58). SETTING: A 22-room
      L&D unit in a women's hospital with 8,500 annual deliveries. PARTICIPANTS: Nurses
      and assistive staff. RESULTS: High-risk tasks were classified in three
      categories. High-exertion tasks included (a) moving patients in labor, delivery,
      recovery (LDR) beds to other locations; (b) breaking delivery beds and applying
      stirrups; (c) assisting dependent patients with mobility in bed; and (d) pushing
      medical equipment and delivery carts. Awkward posture tasks during patient care
      included (a) listening for heart tones; (b) performing difficult vaginal exams;
      (c) keeping the fetal head off of the cord during cord prolapse; and (d)
      assisting with epidurals. Culture of safety tasks included (a) physician requests
      to conduct patient care tasks that put staff at risk for injury; (b) providers
      ignoring broken equipment in the environment; (c) responding to emergent/urgent
      situations without regard to self-posturing to prevent injury; and (d) holding
      patients' legs during delivery at the physician's direction. Several significant
      correlations were noted between demographic variables and high potential for risk
      items. CONCLUSIONS: This study provides the first information about the
      caregiving tasks L&D nurses perceive to be risky for personal injury because of
      their high frequency and exertion or breaches in the culture of safety.

PMID- 22150798
TI  - Chemistry in crime investigation: sodium percarbonate effects on bloodstains
      detection.
AB  - Chemistry plays a leading role in crime investigation. In the study of
      bloodstains, chemical reactions provide the means for the detection. All these
      procedures have been thoroughly studied. However, recently, a new source of error
      has been found: washing stains with "active oxygen" detergents abrogates
      presumptive and human hemoglobin tests for bloodstains (although visible). The
      aim of this investigation was to evaluate the ability of pure sodium percarbonate
      main component of detergents-to abrogate presumptive and human hemoglobin tests.
      Then, a solution to this problem could be found. The results demonstrate that
      pure sodium percarbonate-itself-is able to abrogate all tests, as well as the
      different degrees to which each of them is affected by the product. Consequently,
      faced with a stain of bloody appearance, even the preliminary tests are negative;
      it is advisable to analyze the DNA. Otherwise, the opportunity of obtaining
      valuable information is lost.

PMID- 22150799
TI  - Environmental aridity is associated with cytotype segregation and polyploidy
      occurrence in Brachypodium distachyon (Poaceae).
AB  - * The ecological and adaptive significance of plant polyploidization is not well
      understood and no clear pattern of association between polyploid frequency and
      environment has emerged. Climatic factors are expected to predict cytotype
      distribution. However, the relationship among climate, cytotype distribution and
      variation of abiotic stress tolerance traits has rarely been examined. * Here, we
      use flow cytometry and root-tip squashes to examine the cytotype distribution in
      the temperate annual grass Brachypodium distachyon in 57 natural populations
      distributed across an aridity gradient in the Iberian Peninsula. We further
      investigate the link between environmental aridity, ploidy, and variation of
      drought tolerance and drought avoidance (flowering time) traits. * Distribution
      of diploids (2n = 10) and allotetraploids (2n = 30) in this species is
      geographically structured throughout its range in the Iberian Peninsula, and is
      associated with aridity gradients. Importantly, after controlling for geographic
      and altitudinal effects, the link between aridity and polyploidization occurrence
      persisted. Water-use efficiency varied between ploidy levels, with tetraploids
      being more efficient in the use of water than diploids under water-restricted
      growing conditions. * Our results indicate that aridity is an important predictor
      of polyploid occurrence in B. distachyon, suggesting a possible adaptive origin
      of the cytotype segregation.

PMID- 22150800
TI  - One-stage correction of tetralogy of Fallot associated with anomalous origin of
      the left pulmonary artery from the aorta and aortopulmonary window.
AB  - We report a rare case of tetralogy of Fallot associated with anomalous origin of
      the left pulmonary artery from the aorta and aortopulmonary window. Successful
      one-stage total correction was performed under cardiopulmonary bypass, including
      implantation of the left pulmonary artery, repair of aortopulmonary window, and
      correction of tetralogy of Fallot. The patient experienced an uneventful
      postoperative course and was asymptomatic at one-year follow-up.

PMID- 22150801
TI  - Benefit evaluation in the therapy of chronic wounds from the patients'
      perspective--development and validation of a new method.
AB  - Assessing therapeutic benefit of any drug and medical device is essential in
      registration and cost reimbursement decisions in Germany and in many nations. In
      this study, a method for the assessment of patient-relevant benefits in wound
      therapy was developed and validated. A total of 83 items on treatment benefit
      from the patients' perspective were collected in an open survey, including n = 50
      patients with chronic wounds. The item pool was compiled to a list of 22 items by
      an interdisciplinary panel of experts including patients. The item list is
      presented prior to therapy to assess patient-relevant treatment needs and during
      or after therapy to establish if benefits have been attained. A weighed patient
      benefit index (PBI) is calculated from the items of both questionnaires. The
      instrument was examined for practical feasibility, reliability, and validity in a
      prospective study involving n = 172 patients with acute or chronic wounds treated
      by vacuum-assisted therapy. Validation criteria were: change in generic and
      disease-specific quality of life; judgment of efficacy by patients and
      physicians; treatment satisfaction; patients' willingness to recommend the
      therapy to others. Construct validity was given for all criteria applied.
      Cronbach's alpha was 0.88. The instrument was well-accepted by patients and rated
      relevant for the assessment of benefit in wound treatment.

PMID- 22150802
TI  - Role of novelty and ethanol history in locomotor stimulation induced by binge
      like ethanol intake.
AB  - BACKGROUND: The acute locomotor effects of voluntary ethanol (EtOH) intake in
      mice (stimulation/sedation) might be important behavioral indicators of an
      animals' propensity to engage in EtOH consumption and/or EtOH seeking behaviors.
      Using a binge-like EtOH intake model dubbed "Drinking-in-the-Dark (DID)," we
      recently observed home cage locomotor stimulation in C57BL/6J mice during an
      acute EtOH intake session, but acute home cage locomotor sedation following
      repeated EtOH exposures. To determine the role of novelty and/or EtOH history on
      these previously described locomotor effects, and to determine the relationship
      between these variables on locomotor activity immediately following DID intake,
      we conducted 2 separate experiments. METHODS: In experiment 1, mice were given
      access to either EtOH or water, and locomotor activity was monitored immediately
      afterwards. In experiment 2, mice were given 13 days access to EtOH or water
      solution while home cage locomotor activity was monitored. On the 14th day, half
      of the water consuming animals received EtOH access for the first time. On the
      15th day, all animals received EtOH access, and locomotion was assessed
      afterwards in locomotor activity testing chambers. RESULTS: In experiment 1,
      locomotor activity following DID was positively associated with EtOH intake and
      blood EtOH concentrations (BECs). In experiment 2, the group that received EtOH
      for the first time on the 14th day did not display locomotor stimulation.
      Locomotor activity following DID EtOH intake was positively associated with BECs
      in all groups regardless of EtOH history. CONCLUSIONS: These results suggest that
      (i) DID-induced locomotor stimulation in the home cage may involve relative
      familiarity with the DID procedures, and (ii) locomotor stimulation immediately
      following DID is directly related to the relative concentration of EtOH in blood;
      an effect that is not altered by prior EtOH history. These data add new evidence
      of the pharmacological actions of binge-like EtOH intake, and provide a basis by
      which we may explore the motivation and consequences of such binge consumption.

PMID- 22150803
TI  - Carotid artery stenting without post-dilation.
AB  - INTRODUCTION: The aim of this study is to report the feasibility, safety, and 1
      year restenosis rate of carotid artery stenting (CAS) without post-dilation.
      METHODS: Between April 2006 and November 2009, 254 consecutive patients (68.7 +/-
      8.5 years old, 31% symptomatic) underwent 308 CAS procedures with the intention
      of avoiding post-dilation (eligibility criteria were stenosis of less than 30%
      after stent placement with no overt signs of calcification). Comparison and
      analysis of mid-term clinical outcomes and restenosis rates of CAS with or
      without post-dilation was performed retrospectively. RESULTS: Overall, 27
      patients (study group) were eligible for treatment without post-dilation. No
      significant difference in adverse events was found between the study and control
      group. In the study group, 2 transient ischemic attacks (7.4%) occurred
      immediately after the procedure and no other neurological complications were
      reported during the 30-day, 6-month, and 1-year follow-ups (3 patients died from
      causes unrelated to the procedure). Two asymptomatic restenosis cases were
      diagnosed in the study group within the first 12-months after the procedure
      compared to 16 significant restenosis cases diagnosed in the control group (7.4%
      vs 5.7%, NS). All of them were successfully treated with repeated intervention.
      CONCLUSION: We suggest that CAS without post-dilation is feasible and probably
      safe with a low rate of cerebrovascular events and restenosis in a selected group
      of patients. We also suggest that CAS with postdeployment stenosis of less than
      20% and without overt signs of severe calcification might be performed without
      post-dilation.

PMID- 22150805
TI  - Global variability in diabetes mellitus and its association with body weight and
      primary healthcare support in 49 low- and middle-income developing countries.
AB  - AIMS: In the absence of any previous global comparison, we examined the
      variability in prevalence of diabetes mellitus across 49 developing countries,
      and the associations of diabetes with body weight and primary healthcare support
      using data from the World Health Survey. METHODS: Diabetes mellitus was defined
      by individuals' self-report of a physician diagnosis of diabetes. BMI is the
      weight (kg)/the square of the height (m). Healthcare support was assessed using
      clinical treatment status and whether patients with diabetes followed prescribed
      behaviour changes to control diabetes. Associations of diabetes with BMI and
      diabetes treatment status were analysed cross-sectionally. RESULTS: A total of
      215898 participants were included in the analysis. Age-adjusted prevalence of
      diabetes ranged from 0.27% (Mali) to 15.54% (Mauritius). Participants who were
      underweight (BMI <18.5 kg/m(2) ), overweight (BMI 25-29.9 kg/m(2) ) and obese
      (BMI >= 30 kg/m(2) ) were significantly associated with odds of having diabetes
      as compared with those who were of normal weight (BMI 18.5-24.9 k/m(2) ), with
      corresponding values of multivariate adjusted odds ratios (95% CI) of 1.15 (1.07
      1.24), 1.56 (1.44-1.68) and 2.35 (2.17-2.61), respectively. The overall untreated
      rate of those with diabetes mellitus was 9.6% in the total sample. Patients with
      underweight had the highest diabetes untreated rate, followed by those with
      normal weight, overweight and obesity. CONCLUSION: There are significant
      variations in prevalence of diabetes and primary healthcare support for diabetes
      across low- and middle-income countries. Aggressively preventing abnormal body
      weight and improving healthcare support may play a pivotal role in ameliorating
      the unfavourable epidemic of diabetes in developing countries.

PMID- 22150804
TI  - Clinical benefits and cost-effectiveness of allogeneic red-blood-cell transfusion
      in severe symptomatic anaemia.
AB  - BACKGROUND:   It is well known that blood transfusion is life-saving, but also
      that it carries a serious risk of transmitting viral infections. Introduction of
      new methods of testing for transmissible diseases, blood banking and dispatch
      regulations has considerably increased the cost of blood products. However, the
      clinical benefits and cost-effectiveness of allogeneic red-blood-cell (ARBC)
      transfusion remain assumed yet undetermined. We assessed the clinical benefits
      and cost-effectiveness of ARBC transfusion in severe anaemia. METHODS:   This was
      a multicenter observational study comparing Jehovah's Witness (JW) patients with
      matched ARBC-transfused patients. Inclusion criteria were age >=15 years and
      severe anaemia (haemoglobin <= 80 g/l). Two JW patients with palliative care
      cancer and five JW patients with haemoglobin (Hb) concentration between 70.1 and
      80 g/l, mild symptoms of anaemia and Auckland Anaemia Mortality Risk Score of 0-3
      were excluded. RESULTS:   The entry criteria were met by 103 JW patients and the
      same number of patients treated with ARBC transfusion. ARBC transfusion reduced
      mortality by 94%, shock by 88%, gastrointestinal bleeding by 81%, infective
      complications by 81%, cardiac arrhythmia by 96%, angina by 86%, ischaemic
      myocardial injury by 81%, acute/acute on chronic renal failure by 66%, neurologic
      complications by 92%, delirium by 76%, depression by 91% and syncopal episodes by
      95%. The incremental cost-effectiveness ratio of ARBC transfusion was 2011 US$22
      515 for death prevented. CONCLUSION:   ARBC transfusion in anaemic patients is
      clinically beneficial and cost-effective.

PMID- 22150806
TI  - Clear-cell sarcoma of the soft tissue--a rare diagnosis with a fatal outcome.
AB  - Clear-cell sarcomas account for less than 1% of all soft tissue tumours. They
      most often occur in middle-aged adults as a deeply located lesion with
      predilection to the tendons and aponeuroses. The aim of the present study was to
      show possible influencing factors on the outcome after surgical treatment in a
      detailed case series. We reviewed the medical records of 11 patients with the
      diagnosis of a clear-cell sarcoma of the soft tissue. These cases were analysed
      with regard to age, gender, localisation, tumour size, recurrence free survival
      and overall survival. A minimum follow up of 12 months was achieved. The mean age
      at the point of diagnosis was 47.9 years. Metastases occurred after a mean of
      19.2 months. In the cases with a tumour diameter >5 cm, metastases occurred
      earlier. When treated in a specialist centre, metastases occurred later. Patients
      died a mean of 18.4 months after developing metastatic disease. Patients with
      tumour size >5 cm at the point of primary diagnosis died earlier than patients
      with a tumour size <5 cm. It is important to detect clear-cell sarcomas as soon
      as possible and the final surgical treatment should be performed in a centre
      familiar with the treatment of soft tissue tumours not only to prolong overall
      survival, but also to treat the patient in a multiprofessional team.

PMID- 22150807
TI  - Esthetic evaluation of single-tooth implants in the anterior maxilla following
      autologous bone augmentation.
AB  - OBJECTIVES: Autologous bone augmentation to rebuild compromised alveolar ridge
      contour prior to implant placement allows for favorable three-dimensional implant
      positioning to achieve optimum implant esthetics. The aim of the present study
      was to evaluate peri-implant soft tissue conditions around single-tooth implants
      following bone grafts in the esthetic zone of the maxilla. MATERIALS AND METHODS:
      Sixty patients underwent autologous bone augmentation of deficient maxillary
      sites prior to placement of 85 implants in the esthetic zone. In case of multiple
      implants per patient, one implant was randomly selected. Objective evaluation of
      60 single-tooth implants was performed using the Pink-Esthetic-Score (PES) and
      Papilla Index (PI) and supplemented by subjective patient evaluation, as well as
      clinical and radiologic examination. RESULTS: Objective ratings of implant
      esthetics were satisfactory (median PES: 11, median PI: 2) and significantly
      correlated with high patient satisfaction (mean VAS score: 80%). Both esthetic
      indices demonstrated respectable levels of inter- as well as intra-observer
      agreement. Poor implant esthetics (low PES and PI ratings) were significantly
      associated with increased anatomic crown height, while no influence of horizontal
      implant-tooth distance could be found. CONCLUSIONS: The present investigation
      indicates that favorable esthetic results may be achieved in the augmented
      anterior maxilla. However, bony reconstruction of compromised alveolar ridges
      does not guarantee optimum implant esthetics.

PMID- 22150808
TI  - Is there a future for combinations of implantable devices in human bionics?

PMID- 22150809
TI  - Management of spinal cord stimulators in patients with implantable cardioverter
      defibrillators.
AB  - We report a case of spinal cord stimulation (neurostimulation) as treatment of
      angina pectoris pain in a patient with an implantable cardioverter-defibrillator.
      The precautions taken to avoid inhibition of the demand pace function and avoid
      activation of the shock function by the neurostimulation are discussed.

PMID- 22150810
TI  - A Retrospective, Long-term, Third-Party Follow-up of Patients Considered for
      Spinal Cord Stimulation.
AB  - The objective of this study was to follow up patients considered for spinal cord
      stimulation and assess outcomes and patient selection factors associated with
      outcome. A retrospective study of patients considered for spinal cord stimulation
      was performed. This included three groups: A) those who did not have a temporary
      trial of stimulation, B) those who did not go on to have long-term stimulation
      after a trial, and C) those who did go on to have long-term stimulation after a
      trial. Patient notes were obtained, a structured telephone interview conducted,
      and patients returned a questionnaire. VAS scores, percentage pain reduction
      reported, quality of life reports, Oswestry Disability Index and Hospital Anxiety
      and Depression Indices were recorded. Fifty-two percent of patients who had long
      term stimulation reported 50% or greater pain reduction. In the subset of these
      patients with the diagnosis of failed back surgical syndrome, 51% reported 50% or
      greater pain reduction. Significant improvements in VAS, Oswestry Disability
      Index, and depression were reported pre and post long-term stimulation. There
      were significant differences in the quality-of-life reports between the patients
      who received long-term stimulation (who showed a positive outcome) and those who
      did not (who showed a negative outcome); 80% of patients receiving long-term
      stimulation reported an improvement in their quality of life. Follow-up of a
      cohort of patients receiving long-term stimulation demonstrated some reduction of
      treatment efficacy. Use of a psychological interview aided patient selection, but
      no other factors showed a correlation with reported pain reduction. No serious
      adverse effects were demonstrated. A revision rate of 23.5% occured in long-term
      stimulated patients. We conclude that spinal cord stimulation is an efficacious
      therapy which is not associated with serious side effects. There is some
      reduction in therapeutic efficacy over time. Patients deteriorate without
      treatment.

PMID- 22150811
TI  - Programmable pump for the administration of morphine in the cisterna magna. A new
      approach.
AB  - The implantation of a drug (opioid) infusion system catheter at the level of the
      cisterna magna, connected to an implanted programmable pump (Synchromed pump,
      8611-H, Medtronic, Minneapolis, MN) is the procedure we use most commonly for the
      treatment of craniofacial and upper cervical pain. Our implantation technique,
      which we consider simple and easy to perform, is discussed in this article. Our
      results have been extremely encouraging, without untoward effects occurring.
      Adverse effects are prevented by the close proximity of the catheter tip to the
      pain receptors.

PMID- 22150812
TI  - Spinal morphine in nonmalignant chronic pain: a retrospective study in 39
      patients.
AB  - It was the purpose of this study to retrospectively test the safety and efficacy
      of the use of intraspinal analgesics in a diverse population of patients with
      chronic nonmalignant pain. This study was conducted in 39 patients, refractory to
      conventional therapies for intrathecal therapy. Twenty-two patients had
      neuropathic pain and 17 had nociceptive pain. The mean follow-up of this patient
      population was 2.2 years with a range of 36 months to 6.5 years. Analgesia with
      intraspinal morphine, initial and final dose of intraspinal agents used,
      stability of morphine dose over time, and side effects and complications with or
      without bupivacaine and/or clonidine was assessed after 6 months of treatment,
      and at the end of study. After 6 months, three patients discontinued the study
      for differing reasons, 28 patients (77.8%) reported excellent results, and five
      patients (14%) reported good results. One patient reported no pain relief with
      intraspinal morphine and bupivacaine and five patients reported insufficient or
      no pain relief. At final assessment, 20 patients (55.6%) reported excellent
      results with no differences based on pain type or pain syndrome and eight
      patients (22.2%) reported good analgesia. Morphine doses remained stable
      throughout treatment, with an average dose of 2 mg per patient. Ninety-one
      percent of patients were satisfied with the method used and considered it
      superior to all previous therapeutic techniques tried, improving their quality of
      life. As for complications, one patient developed a clostridial infection during
      the immediate postoperative period which required pump removal and one patient
      developed severe urinary retention requiring system removal. There were three
      catheter obstructions (two in the same patient) and one catheter disconnection.
      Other patient-reported side effects were not considered significant by the
      authors to be mentioned here. After more than 6 years of experience with spinal
      infusion of morphine, either alone or admixed with other spinal analgesics, in
      patients with pain of nonmalignant origin, we consider the technique to be
      helpful in selected patients not responding to oral treatment or when untoward
      side effects exist with oral treatment. The advantages, as regards to analgesic
      efficacy and quality of life, clearly outweigh the drawbacks of the long-term use
      of spinal morphine.

PMID- 22150813
TI  - Operating principles and clinical implications of constant flow pumps.
AB  - Intrathecal drug therapy has become an indispensable tool in the treatment of
      many different neurologic disorders. It allows targeted infusion of small
      quantities of drugs, thereby increasing effectiveness while reducing unwanted
      side effects typically seen in oral drug administration. The following paper
      discusses the current technology in constant rate intrathecal drug-infusion
      delivery systems and the effect of pressure and temperature on flow rate
      accuracy.

PMID- 22150814
TI  - Evolving patterns of spinal cord stimulation in patients implanted for
      intractable low back and leg pain.
AB  - The objective of this study was to examine the programming strategies used in
      patients with intractable low-back pain treated with epidural spinal cord
      stimulation (SCS) utilizing paddle electrodes and a radio frequency (RF)
      stimulator. Programming strategies were examined in a group of patients implanted
      with a 16-contact paddle electrode and a dual channel RF receiver to treat
      chronic low-back pain. Baseline data included previous surgical history
      information, leg and low back pain severity and characteristics, and routine
      demographic information. Outcome measurements included the visual analog scale
      (VAS) (1), patient pain relief rating scale, and programming parameters. Patients
      rated their pain relief on a 5-point scale where 4 = excellent, 3 = good, 2 =
      fair, 1 = poor and 0 = none. Success was determined to be a pain relief score of
      "fair" or above. Data were collected during patient visits or by mail, at
      approximately 6, 12, and 24 months, postoperatively. Immediate postop data were
      available in 16 patients, 6-month data in 21 patients, 1-year data in 20
      patients, and 2-year data in 10 patients, and analyzed for the purposes of
      examining programming strategies. The most common location for the tip of the
      electrode (lead) was found to be in the middle of the 8th thoracic vertebrae (N =
      26). At the immediate postop assessment, the majority of cathodes were activated
      in the upper half of T9. By the 6-month follow-up, the majority of cathodes had
      shifted to the bottom of T9 and top of T10. Overall 88% of cathode locations were
      changed at one or more study visits. At 2 years, 86% of the programs used four or
      more active contacts. At 6 months, 83% of the patients reported that the therapy
      was a success, at 1 year, success was 94%, and by 2 years, success was 75%. Both
      SCS and chronic pain are dynamic processes. Complex pain patterns, such as the
      ones of patients who have pain in the low back and in one or both lower
      extremities, require a high degree of flexibility in the implanted SCS system.
      The system must provide the capability to redirect the current electronically
      over at least two segments of the spinal canal, to electronically steer the
      current in a medio-lateral direction, and to activate multiple electrical
      contacts simultaneously. The willingness and ability to provide extensive
      reprogramming in the long term follow-up is also of the utmost importance. Pain
      and its treatment with SCS is a dynamic process.

PMID- 22150816
TI  - Letter to the Editor Comments to the Guest Editorial by Dr. DeJongste.

PMID- 22150815
TI  - Breathing induced by abdominal muscle stimulation in individuals without
      spontaneous ventilation.
AB  - The purpose of the study was to determine if functional electrical stimulation of
      abdominal muscles (FESAM) could maintain pulmonary ventilation at acceptable
      levels in individuals with spinal cord injury (SCI) who are unable to breathe
      spontaneously. This is the first published investigation of this technique in
      this subject population. This case series study included three individuals with
      SCI; two were on mechanical ventilation (MV), and one used mechanical ventilation
      and also had an implanted phrenic nerve stimulator (PNS). Using surface
      electrodes, stimulation was applied to the rectus abdominis and lateral group of
      abdominal muscles. Repetitive trains of pulses produced a breathing frequency of
      20 breaths/min. The longest periods of breathing using only FESAM-supported
      ventilation for the three subjects were 30, 40, and 210 s, respectively. Airflow
      at the mouth and volumes were measured with a pneumotachograph and/or
      optoelectronic plethysmography. Oxygenation was monitored with a pulse oximeter.
      The tidal volumes generated exclusively by FESAM were sufficient to maintain
      adequate oxygenation during the periods of stimulation. When oxygenation measured
      with pulse oximetry dropped to 92% saturation, FESAM was discontinued, and MV or
      PNS was resumed. This is the first report of achieving successful ventilation in
      individuals with SCI who have zero tidal volume using FESAM. These preliminary
      results indicate the clinical potential of FESAM as an additional tool in the
      armamentarium of supported ventilation.

PMID- 22150817
TI  - Letter to the editor.

PMID- 22150818
TI  - Clinical anticipation in Japanese families of benign adult familial myoclonus
      epilepsy.
AB  - The clinical anticipation in Japanese benign adult familial myoclonus epilepsy
      (BAFME), defined as earlier onset age of either cortical tremor or generalized
      seizures or new appearance of those symptoms in the next generation, remains
      unknown. The onset age and the degree of both cortical tremor and generalized
      seizures were investigated in nine patients of four BAFME families (mean age:
      46.6 +/- 18.7 years). Clinical anticipation in the onset age of cortical tremor
      or generalized seizures was observed in three families, and generalized seizures
      newly appeared in the next generation in those two families and in another
      family. Clinical anticipation was observed in four families, which suggests the
      clinical progression over generation in Japanese BAFME families.

PMID- 22150819
TI  - A pilot randomised controlled trial of brief versus twice weekly versus standard
      supervised consumption in patients on opiate maintenance treatment.
AB  - INTRODUCTION AND AIMS: Methadone maintenance remains the mainstay of treatment
      for opiate dependence in Scotland. Guidelines recommend supervised self
      administration for at least 3 months, yet this is often interpreted as long-term
      supervision. However, there is no evidence base for deciding the optimal period
      of supervision. We tested the feasibility of conducting a randomised controlled
      trial (RCT) of different supervision models. DESIGN AND METHODS: Three armed
      pilot RCT, set in three Scottish treatment areas, recruited opiate-dependent
      patients who had received methadone treatment for 3 months. Participants were
      randomised to: (i) no supervision; (ii) twice weekly supervision; or (iii) daily
      supervision for further 3 months. As a pilot, key process measures were:
      recruitment rates, follow-up rates and treatment fidelity. We also wanted to
      estimate effect sizes of two co-primary outcomes for a full RCT: treatment
      retention and illicit heroin use. The recruitment target was 60 participants.
      RESULTS: One hundred and two eligible patients were identified, 60 (59%)
      participated, and 46 followed up (77%). Study fidelity was good with two
      participants moving group. Those randomised to no supervision were significantly
      happier with their group allocation. No significant differences were found in
      primary outcomes, although retention decreased with increased supervision, while
      illicit heroin use was least in those most supervised. DISCUSSION AND
      CONCLUSIONS: It is possible to recruit and randomise participants to an RCT
      comparing different forms of supervised consumption. Pilot data suggest increased
      supervision may reduce illicit heroin use, but may decrease retention. This
      should now be tested in a large-scale multicentre RCT.

PMID- 22150820
TI  - Antibodies to citrullinated protein antigen are not biomarkers for Grave's
      ophalmopathy.

PMID- 22150821
TI  - Hypoxia-inducible factor 1 activation from adipose protein 2-cre mediated
      knockout of von Hippel-Lindau gene leads to embryonic lethality.
AB  - von Hippel-Lindau protein, an E3 ubiquitin ligase from the von Hippel-Lindau
      (Vhl) gene, inhibits the transcriptional activity of hypoxia-inducible factor
      1alpha in cells. To gain insight into the hypoxia-inducible factor 1alpha
      signalling pathway in adipose tissue, a study was conducted to generate fat
      specific Vhl knockout mice. Cre-recombinase (Cre)/locus of crossover in P1(loxP)
      technology was used in the knockout study. The mice carrying floxed-Vhl alleles
      were crossed with adipose protein 2 (aP2)-Cre mice, in which the Cre gene is
      driven by the aP2 (fatty acid binding protein 4) gene promoter. The homozygous
      knockout mice exhibited embryonic lethality at E14.5-E18.5. The homozygous
      embryos suffered from haemorrhages in the brain and liver. Hypoxia-inducible
      factor 1alpha protein and its target gene protein, vascular endothelial growth
      factor, increased in the brain and liver. Endothelial proliferation and capillary
      leakage were observed in the tissues. Heterozygous knockout mice appeared normal
      in development, growth and reproductivity. beta-galactosidase reporter mice were
      used in the analysis of tissue-specificity of Cre in aP2-Cre mice. Strong Cre
      activity was observed in the dorsal hindbrain region and vertebrae of E12.5
      embryos. These results suggest that in the aP2-Cre mice, the recombinase activity
      is expressed in the central nervous system of the embryos. Central and peripheral
      haemorrhages are responsible for the embryonic lethality in the homozygous
      knockout mice.

PMID- 22150822
TI  - Do aquatic barriers reduce male-mediated gene flow in a hybrid zone of the common
      shrew (Sorex araneus)?

PMID- 22150823
TI  - Dl-alpha-tocopherol enhances the herbicide 1,1'-dimetyl-4,4'-bipyridium
      dichloride (paraquat, PQ) genotoxicity in cultured anuran leukocytes.
AB  - This cytogenetic and pharmacological study attempts to clarify genotoxicity
      enhancement-effect of dl-alpha-tocopherol (one form of vitamin E) in combination
      with the herbicide 1,1'-dimetyl-4,4'-bipyridium dichloride (paraquat, PQ) on
      cultured anuran leukocytes using the superoxide dismutase-mimic Mn(III)tetrakis(1
      methyl-4-pyridyl)porphyrin (Mn(III)TMpyP), the hydrogen peroxide-scavenger
      catalase and the electron donor nicotinamide adenine dinucleotido phosphate
      (NADPH). PQ only was found to induce structural chromosomal damage in cultured
      anuran leukocytes in a dose-dependent manner. PQ plus NADPH, which served as
      positive control, enhanced the genotoxic effect of PQ. Dl-alpha-tocopherol only
      did not induce any structural chromosomal damage in the leukocytes. PQ plus dl
      alpha-tocopherol, however, enhanced the genotoxic effect of PQ. PQ plus
      Mn(III)TMpyP, PQ plus catalase and PQ plus Mn(III)TMpyP plus catalse suppressed
      the genotoxic effect of PQ. Furthermore, PQ plus dl-alpha-tocopherol-enhanced
      chromosomal damage was also inhibited by Mn(III)TMpyP plus catalase. These
      results suggest that dl-alpha-tocopherol in combination with PQ functions as an
      electron donor to PQ.

PMID- 22150824
TI  - Apomixis in different ploidy levels of cassava.
AB  - Two polyploid hybrids between cassava (Manihot esculenta) cultivar 307-2 and its
      wild relatives M. glaziovii and M. anomala, were studied to examine the
      relationship between ploidy level and the production of seeds without
      fertilization. A clearing method was applied to assess ovule sizes as an
      indication of multiembryony. The diploid cultivar 307-2 had regular 18 bivalents
      at meiotic metaphase 1 while the polyploid types showed chromosome configurations
      varying from 3 to 4 quadrivalents and 28 to 30 bivalents. A total of 14% of
      studied ovules of the polyploid hybrid involving M. glaziovii were multiebryonic,
      while the percentage of multiembryony was as low as 2% in the polyploid hybrid M.
      anomala*M. esculenta. Diploid hybrid types did not show any multi embryony.
      Adventitious embryos were found and documented for the first time in polyploid
      hybrids M. esculenta*M. glaziovii. The association of multiple embryo formation
      with ovary size and pollination showed that apomictic embryos form independently
      from fertilization. Simple iodized carmine stain for measuring pollen viability
      proved as efficient as the sophisticated Alexander method.

PMID- 22150825
TI  - Improving the flexibility and efficiency of phase II designs for oncology trials.
AB  - Phase II trials in oncology are usually conducted as single-arm two-stage designs
      with binary endpoints. Currently available adaptive design methods are tailored
      to comparative studies with continuous test statistics. Direct transfer of these
      methods to discrete test statistics results in conservative procedures and,
      therefore, in a loss in power. We propose a method based on the conditional error
      function principle that directly accounts for the discreteness of the outcome. It
      is shown how application of the method can be used to construct new phase II
      designs that are more efficient as compared to currently applied designs and that
      allow flexible mid-course design modifications. The proposed method is
      illustrated with a variety of frequently used phase II designs.

PMID- 22150826
TI  - The Arabidopsis aquaporin PIP1;2 rules cellular CO(2)  uptake.
AB  - The membrane CO(2) flux into Arabidopsis mesophyll cells was studied using a
      scanning pH microelectrode. Arabidopsis thaliana mesophyll cells were exposed to
      photosynthesis-triggering light intensities, which induced cellular CO(2) uptake.
      Data obtained on a AtPIP1;2 T-DNA insertion line indicated that under these
      conditions, cellular CO(2) transport was not limited by unstirred layer effects
      but was dependent on the expression of the aquaporin AtPIP1;2. Complementation of
      the AtPIP1;2 knockout restored membrane CO(2) transport levels to that of
      controls. The results provide new arguments for the ongoing debate about the
      validity of the lipid bilayer model system and the Meyer - Overton rule for
      cellular gas transport. In conclusion, we suggest a modified model of molecular
      gas transport mechanisms in living cells.

PMID- 22150827
TI  - Young women's beliefs regarding human papillomavirus.
AB  - OBJECTIVE: To describe young women's perceptions of human papillomavirus (HPV)
      using the Common Sense Model and examine whether perceptions differ based on
      history of HPV diagnosis or sexually transmitted disease (STD) testing. DESIGN:
      Cross-sectional, survey data. SETTING: Four women's health clinics and one
      university classroom. PARTICIPANTS: Three hundred and two women ages 18-24.
      METHODS: Young women's beliefs regarding HPV were measured using the HPV
      Representations of Sexually Transmitted Diseases (RoSTD) survey. RESULTS: Most
      survey respondents believed HPV diagnosis was likely to result in cancer and
      death. Negative beliefs about the psychosocial consequences of HPV diagnosis were
      common. Compared to those who had not been diagnosed with HPV (or had never
      received STD testing), young women with a history of HPV diagnosis or STD testing
      had less serious and more accurate beliefs about HPV. CONCLUSION: Young women
      tend to have misconceptions about HPV in addition to noteworthy concerns about
      the psychosocial consequences of HPV diagnosis. Clinical attention to young
      women's beliefs about HPV may provide direction for improving the delivery of
      patient-centered education and counseling about this exceedingly common illness.

PMID- 22150828
TI  - What can history do for bioethics?
AB  - This article details the relationship between history and bioethics. I argue that
      historians' reluctance to engage with bioethics rests on a misreading of the
      field as solely reducible to applied ethics, and overlooks previous enthusiasm
      for historical perspectives. I claim that seeing bioethics as its practitioners
      see it - as an interdisciplinary meeting ground - should encourage historians to
      collaborate in greater numbers. I conclude by outlining how bioethics might
      benefit from new histories of the field, and how historians can lend a fresh
      perspective to bioethical debates.

PMID- 22150829
TI  - Post operative infection, pyrexia and perioperative antimicrobial drug use in
      surgical colic patients.
AB  - REASONS FOR PERFORMING STUDY: Infections are common complications in post
      operative colic patients. It is the impression of some surgeons that pyrexia in
      the early post operative period is a sign of infection and appropriate timing of
      perioperative antimicrobials will decrease the incidence of post operative
      infection. OBJECTIVE: To determine the association between 1) post operative
      pyrexia and development of infection and 2) perioperative antimicrobial drug use
      and infection rate in post operative colic patients. METHODS: Medical records of
      patients undergoing surgical treatment for colic were reviewed. Horses recovering
      from surgery and surviving >48 h were included. Data relating to case details,
      duration of surgery, post operative infection, peri- and post operative
      antimicrobial administration, presence, intensity and duration of pyrexia, were
      recorded. Data were analysed using standard statistical methods for simple
      comparisons between groups and by logistic regression for more complex
      comparisons. RESULTS: One-hundred-and-thirteen horses were included in the final
      analyses, 48 (43%) of which were diagnosed with a post operative infection.
      Duration of surgery and anaesthesia were associated with post operative
      infection. Eighty-five percent of horses (n = 96) exhibited pyrexia (rectal
      temperature >38.3 degrees C) post operatively. Peak temperature >39.2 degrees C,
      time post surgery to peak temperature >48 h and duration of pyrexia >48 h were
      significantly associated with infection. In a combined model, time to first
      pyrexic >48 h post surgery, peak temperature and time to peak >48 h were equally
      weighted and the model's positive predictive value for post operative infection
      was 72%. Timing and dose rate of preoperative antimicrobials were not associated
      with infection but duration of post operative antimicrobial drug use was.
      CONCLUSION AND CLINICAL RELEVANCE: Slight to mild pyrexia (38-39.4 degrees C) in
      the early post operative period is not necessarily associated with impending
      bacterial infection in colic patients and the use of antimicrobials in these
      patients may be costly and unnecessary.

PMID- 22150830
TI  - Plant Aurora kinases play a role in maintenance of primary meristems and control
      of endoreduplication.
AB  - * The conserved family of Aurora kinases has multiple functions during mitosis.
      The roles of plant Aurora kinases have been characterized using inhibitor
      treatments. * We down-regulated Aurora kinases in Arabidopsis thaliana using RNA
      interference (RNAi). We carried out a detailed phenotypic analysis of Aurora RNAi
      plants, biochemical and microscopic studies of AtAurora1 kinase together with
      AtTPX2 (targeting protein for Xklp2) and gamma-tubulin. * Cell division defects
      were observed in plants with reduced expression of Aurora kinases. Furthermore,
      the maintenance of primary meristems was compromised and RNAi seedlings entered
      endoreduplication prematurely. AtAurora1, its activator AtTPX2, and gamma-tubulin
      were associated with microtubules in vitro; they were attached to regrowing
      kinetochore microtubules and colocalized on spindle microtubules and with a
      subset of early phragmoplast microtubules. Only the AtAurora1 kinase was
      translocated to the area of the cell plate. * RNAi silencing of Aurora kinases
      showed that, in addition to their function in regulating mitosis, the kinases are
      required for maintaining meristematic activity and controlling the switch from
      meristematic cell proliferation to differentiation and endoreduplication. The
      colocalization and co-fractionation of AtAurora1 with AtTPX2, and gamma-tubulin
      on microtubules in a cell cycle-specific manner suggests that AtAurora1 kinase
      may function to phosphorylate substrates that are critical to the spatiotemporal
      regulation of acentrosomal microtubule formation and organization.

PMID- 22150831
TI  - The antibacterial properties of docosahexaenoic omega-3 fatty acid against the
      cystic fibrosis multiresistant pathogen Burkholderia cenocepacia.
AB  - Burkholderia cepacia complex (Bcc) bacteria are opportunistic pathogens that
      cause multiresistant pulmonary infections in patients with cystic fibrosis (CF).
      In this study, we evaluated the in vitro antimicrobial efficacy of eight
      unsaturated fatty acids against Burkholderia cenocepacia K56-2, a CF epidemic
      strain. Docosahexaenoic acid (DHA) was the most active compound. Its action can
      be either bacteriostatic or bactericidal, depending upon the concentration used.
      The effect of DHA was also evaluated on two others B. cenocepacia clinical
      isolates and compared with one representative member of all the 17 Bcc species.
      To test whether DHA could have a therapeutic potential, we assessed its efficacy
      using a Galleria mellonella caterpillar model of B. cenocepacia infection. We
      observed that the treatment of infected larvae with a single dose of DHA (50 mM)
      caused an increase in the survival rate as well as a reduced bacterial load.
      Moreover, DHA administration markedly increases the expression profile of the
      gene encoding the antimicrobial peptide gallerimycin. Our results demonstrate
      that DHA has in vitro and in vivo antibacterial activity against Bcc
      microorganisms. These findings provide evidence that DHA may be a useful
      nutraceutical for the treatment of CF patients with lung infections caused by
      antibiotic multiresistant Bcc microorganisms.

PMID- 22150832
TI  - Healing of chronic venous leg ulcers could be affected by an interaction of the
      hemochromatosis gene polymorphism HFE H63D with the strength of compression
      treatment--a re-analysis of patients from previous studies.

PMID- 22150833
TI  - Physicians, industry, and science: moving forward as neuromodulation matures.

PMID- 22150834
TI  - Changes in glucose metabolism in cerebral cortex and cerebellum correlate with
      tremor and rigidity control by subthalamic nucleus stimulation in Parkinson's
      disease: a positron emission tomography study.
AB  - Objective.  Employing [(18) F]fluorodeoxyglucose (FDG) positron emission
      tomography (PET) to assess the correlation between the effect of deep brain
      stimulation (DBS) on the subthalamic nucleus (STN) and the regional cerebral
      metabolic rate of glucose (rCMRGlc) in advanced Parkinson's disease patients (N =
      8). Materials and Methods.  On the basis of patients' diary records, we performed
      FDG-PET during the off-period of motor activity with on- or off-stimulation by
      STN-DBS on separate days and analyzed the correlation between changes in motor
      symptoms and alterations in the rCMRGlc. Result.  When FDG-PET was performed, the
      motor score on the unified Parkinson's disease rating scale (UPDRS) was 64% lower
      with on-stimulation than with off-stimulation (p < 0.001, Wilcoxon single-rank
      test). STN-DBS increased the rCMRGlc in the posterior part of the right middle
      frontal gyrus, which corresponded to the premotor area, and the right anterior
      lobe of the cerebellum (p < 0.005, paired t-test). No region exhibited a decrease
      in rCMRGlc. Among the items of the UPDRS motor score, the changes in resting
      tremor and rigidity of the left extremities showed a significant correlation with
      the changes in rCMRGlc observed in the right premotor area (p < 0.02 and p <
      0.05, respectively, Spearman's rank correlation). Conclusions.  STN-DBS either
      activates the premotor area or normalizes the deactivation of the premotor area.
      These FDG-PET findings obtained are consistent with the idea that STN-DBS
      modifies the activities of neural circuits involved in motor control.

PMID- 22150835
TI  - Effects of spinal cord stimulation on peripheral blood circulation in rats with
      streptozotocin-induced diabetes.
AB  - Objective.  The aim of this study was to investigate the effects of spinal cord
      stimulation (SCS) on peripheral circulation in rats with streptozotocin (STZ)
      induced diabetes. Materials and Methods.  Four weeks after streptozotocin or
      vehicle was injected (i.p.) in male Sprague-Dawley rats, SCS-induced vasodilation
      was examined. Results.  Plasma glucose concentration was significantly higher in
      diabetic rats than in the control animals. Motor threshold (MT) was significantly
      higher in diabetic rats than in control rats. SCS-induced vasodilation was
      attenuated at 90% of the MT, but not at 30% and 60% of MT in diabetic rats when
      compared to control rats (p < 0.001, N = 13). Furthermore, increasing SCS from
      30% to 90% of MT typically produced a progressive increase in blood flow in
      control rats but not in diabetic rats (p < 0.01, N = 13). Conclusion.  This study
      suggested that SCS-induced vasodilation improves peripheral blood flow, although
      the pathways were partially impaired in the diabetic condition.

PMID- 22150836
TI  - Spinal Cord Stimulation Modulates Visceral Nociception and Hyperalgesia via the
      Spinothalamic Tracts and the Postsynaptic Dorsal Column Pathways: A Literature
      Review and Hypothesis.
AB  - Introduction.  Early animal and human evidence existed for a postsynaptic dorsal
      column (PSDC) pathway for visceral nociception that, when lesioned, decreased
      pain of terminal illness. There have been recent anecdotal reports in the
      literature that spinal cord stimulation (SCS) reduces pain of visceral
      nociception. We present here a review of the literature supporting a hypothesis
      that SCS might work by modulating information through the spinothalamic tracts
      (STT) and PSDC. Methods.  A review of the relevant literature regarding
      nociception, nociceptive transmission, visceral sensitization, and the "brain
      gut" axis; and SCS was performed as a foundation for this hypothesis. Key words
      used for this review of databases and nonindexed relevant journals included
      visceral pain, visceral nociception, visceral hyperalgesia, visceral neuropathic
      pain, visceral sensitization, "brain-gut" axis, SCS, PSDC pathway, and STTs.
      Results.  An abundance of both clinical and scientific literature suggests the
      neuropathic and sensitized nature of chronic visceral nociception. There is also
      evidence that there may be an interaction between the PSDC pathway and lateral
      spinothalamic tracts (LSTT) that might be operant in the preclinical and
      anecdotal clinical evidence that SCS ameliorates the pain of visceral
      nociception. Conclusions.  Chronic visceral nociception may be secondary to
      visceral sensitization and hyperalgesia and can be affected by the spinal cord
      and brain, the "brain-gut" axis. There is preclinical evidence and clinical
      anecdotes that this nociceptive information is transmitted in the central nervous
      system through the PSDC pathway and LSTT and that SCS decreases pain of visceral
      nociception. It may be that SCS works by modulation of the above pathways.

PMID- 22150837
TI  - Dyskinesia in Parkinson's disease treated by deep brain stimulation once
      electrode position was revised: case report.
AB  - Repositioning of a subthalamic nucleus deep brain stimulation lead alleviated a
      parkinsonian patient's dyskinesias without the need for parkinsonian medication
      reduction. After the initial placement and programming, the patient was doing
      well. During repair of a skin erosion, the lead moved ventral and the patient
      developed severe dyskinesias and, when the deep brain stimulation system was on,
      diplopia. Multiple reprogramming attempts did not alleviate these problems. The
      electrode was moved dorsally by about 6 mm. Intraoperatively the patient's
      dyskinesias stopped with no diplopia with the stimulator on. Two years after the
      revision the patient is doing very well.

PMID- 22150838
TI  - Histological alterations induced by electrode implantation and electrical
      stimulation in the human brain: a review.
AB  - Objectives.  Electrical brain stimulation is used as a treatment for patients
      with intractable chronic pain and movement disorders. However, the implantation
      of electrodes and electrical stimulation may induce histological changes around
      the electrode tip. We aimed to review the histological changes in humans that
      were electrically stimulated in the brain. Methods.  We traced 26 autopsy studies
      of which 19 patients received cerebellar stimulation and 37 patients deep brain
      stimulation. Results.  Electrode implantation and electrical stimulation induced
      in part of the cases formation of a fibrous sheath around the electrode, loss of
      fairly large neurons, and limited gliosis. Macroscopic lesions were present in
      only some cases, mostly due to pulling at the extension cable in the
      postoperative evaluation period preceding definite implantation of the electrode
      wire and stimulator. Conclusions.  Electrical brain stimulation induces
      histological changes in some patients. According to electrical brain stimulation
      studies in animals, these changes can be related to the charge and charge density
      per phase (and their interaction).

PMID- 22150839
TI  - A new spinal cord stimulation system effectively relieves chronic, intractable
      pain: a multicenter prospective clinical study.
AB  - Objectives.  A prospective, open label, multicenter clinical trial confirmed the
      functionality of a new spinal cord stimulation (SCS) system for the treatment of
      chronic, intractable pain of the trunk and/or limbs. Materials and Methods. 
      Sixty-five subjects tested a rechargeable 16-channel SCS system with individual
      current control of each contact on one or two percutaneous eight-contact epidural
      leads. After baseline measurements, subjects were tracked on pain ratings and
      complication rates for up to 18 months. Results.  After a trial period, 75% of
      subjects underwent permanent implantation of the entire SCS system. More than one
      half the implanted subjects experienced 50% or greater relief of pain after
      permanent implantation; some subjects reported relief of 90% or more of their
      pain. The most common complications after permanent implantation were lead
      migration, uncomfortable stimulation, and component failure; most resolved after
      reprogramming or device replacement. Conclusions.  The new SCS system provided
      good pain relief to a majority of subjects, and the results confirm a favorable
      safety and efficacy profile for the SCS system.

PMID- 22150840
TI  - Peripheral Nerve Field Stimulation for the Treatment of Chronic Low Back Pain:
      Preliminary Results of Long-Term Follow-up: A Case Series.
AB  - Objective.  Our objective was to determine the efficacy of peripheral nerve field
      stimulation (PNFS) for the treatment of chronic lower back pain. PNFS is becoming
      increasingly recognized as a safe, minimally invasive, and easily reversible
      treatment for a variety of chronic pain conditions. Chronic low back pain is a
      common cause of disability and one that is difficult to treat effectively. We
      hypothesized that PNFS would be a safe, effective alternative for patients with
      chronic low back pain, which has not been previously reported. Materials and
      Methods.  Six patients with chronic low back pain who had failed conventional
      therapies were implanted in the subcutaneous tissues of the low back region with
      neurostimulation leads. Leads were placed superficially in the region of maximum
      pain, as identified by each individual patient. Patients initially underwent a
      trial of stimulation to assess response, and a permanent system was subsequently
      implanted if patients reported greater than 50% pain relief in the low back
      during the trial. Results.  In each case presented here, PNFS enabled patients to
      decrease their pain medication and increase their level of activity. The patients
      all reported reduction in pain as measured by visual analog scale scores and an
      improved quality of life. Conclusion.  We conclude that PNFS is a safe and
      effective alternative treatment for patients with chronic low back pain, and
      should be considered in this population.

PMID- 22150841
TI  - The feasibility of functional electrical stimulation indoor rowing for high
      energy training and sport.
AB  - Objectives.  To explore the potential of functional electrical stimulation (FES)
      assisted indoor rowing to enable spinal cord individuals to participate in indoor
      rowing competitions and to achieve high exercise intensities and volumes.
      Materials and Methods.  Six spinal cord injured subjects used a newly developed
      four-channel, manually controlled, FES-rowing system for training and
      competition. Results.  Four paraplegics and two quadriplegics used the newly
      developed FES-rowing system for long-term training. Moreover, they competed
      successfully with able-bodied rowers in major indoor rowing events; the 2004-2006
      British and 2006 World Indoor Rowing Championships. The current best FES-rowing
      time for the official 2000 meter distance is 10:28. Steady state VO(2)  values of
      2.5 L/min (> 35 mL/kg/min) and weekly training volumes of 1150 kcal/week (4814
      kJ/week) have been achieved. Conclusions.  For the first time, individuals with
      spinal cord injury have participated, on an equal basis, in major indoor rowing
      events using FES. The FES-rowers attained high levels of exercise volume and
      intensity. These levels are higher than have been previously reported for FES
      exercise and are similar to those that have been associated with significant
      health benefits in the general population.

PMID- 22150843
TI  - Surgical management of left ventricular outflow tract obstruction.
AB  - BACKGROUND: Left ventricular outflow tract obstruction (LVOTO) is caused by a
      spectrum of lesions. This study was performed to determine the outcomes of
      surgical management of LVOTO. METHODS: All patients who had surgery of the LVOT
      between 2002 and 2010 were retrospectively reviewed. RESULTS: There were 103
      consecutive patients with median age 6.8 years (range 8 days to 62 years).
      Fourteen patients had simple subaortic membrane. Eighty-nine patients had complex
      LVOTO including fibromuscular obstruction (n = 53), tunnel obstruction (n = 22),
      hypertrophic cardiomyopathy/muscular obstruction (n = 15), and anomalies of the
      mitral subvalvar apparatus (n = 13). There were no early deaths. Mean LVOT
      gradient decreased from 33 mmHg (range 1 to 108 mmHg) to 6 mmHg (range 0 to 45
      mmHg) (p < 0.001). Median follow-up was 3.8 years (range 0.9 to 8.5 years). There
      were three late deaths. Cumulative survival at one, three, and five years was 96%
      (95% CI 89% to 99%). All patients are in New York Heart Association classes I-II.
      Ten patients required reoperation (three for recurrent/residual LVOTO). Freedom
      from reoperation was 94%, 90%, and 78% at one, three, and five years (95% CI 86%
      to 98%, 80% to 95%, and 59% to 89%, respectively). No patient with complex LVOTO
      who had release of the fibrous trigones required reoperation [0% (0/26) vs. 16%
      (10/63) (p = 0.031)]. Factors associated with increased reoperation risk were
      interrupted aortic arch (OR 6.4, p = 0.22), atrioventricular septal defect (OR
      15.4, p = 0.008), and higher mean LVOT gradient at discharge (OR 1.08, p =
      0.023). CONCLUSIONS: Utilizing a multitude of operative strategies for surgery of
      the LVOT results in favorable early and midterm outcomes. Residual LVOTO and
      original cardiac diagnosis are associated with increased reoperation risk.
      Release of the fibrous trigones decreases reoperation risk in patients with
      complex LVOTO.

PMID- 22150842
TI  - Successful implementation of cooperative handling eliminates the need for
      restraint in a complex non-human primate disease model.
AB  - BACKGROUND: Streptozotocin-induced diabetic non-human primates are used to study
      efficacy and safety of innovative immunosuppression after islet transplantation.
      We implemented a training program for medical management of a chronic disease
      state. METHODS: Cooperation with hand feeding and drinking, shifting, and limb
      presentation were trained utilizing predominately positive but also negative
      reinforcement in 52 animals compared with 28 macaques subjected to conventional
      physical and/or chemical restraint. The success and timing of behavior
      acquisition was evaluated in a representative subset of 14 animals. RESULTS: Over
      90% of animals were successful in behavior acquisition. Programmatically this
      resulted in complete elimination of chair restraint and negligible requirement
      for sedation. About half of the trained animals had no-to-moderate thymic
      involution, indicative of a substantial reduction in stress. CONCLUSION:
      Cooperative handling enhances animal well-being. This contributes to validity of
      scientific results and eliminates model-induced confounding that can obstruct
      interpretation of safety and efficacy data.

PMID- 22150844
TI  - N-terminal pro-B-type natriuretic peptide is associated with severity of the
      coronary lesions in unstable angina patients with preserved left ventricular
      function.
AB  - OBJECTIVES: To evaluate the association between N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) values and the severity of coronary lesions at angiography in
      unstable angina patients with preserved left ventricular function. METHODS: A
      total of 133 patients with primary diagnosis of unstable angina were enrolled
      into this study. NT-proBNP level was determined before the angiography and
      Gensini score, a measurement of extent of myocardial ischemia, was calculated
      after the angiography by experienced cardiologists. Patients with >50% stenosis
      of the left main or 75% stenosis of one or more coronary branches with diameter
      >2 mm were defined as "angiography positive" and turned to percutaneous coronary
      intervention. RESULTS: There was a significant difference of circulating NT
      proBNP level between the angiography positive and negative groups and the median
      NT-proBNP values were 367.5 pg/mL and 112 pg/mL, respectively (P < 0.001). A
      significant correlation was observed between log NT-proBNP and log Gensini score
      (P < 0.001). NT-proBNP level was a predictor of angiography positive result and
      the area under the receiver operating characteristic curve was 0.776 (95% CI
      0.693-0.858). CONCLUSIONS: NT-proBNP level was found to be higher with the
      severity of myocardial ischemia. However, the ability of NT-proBNP to identify
      clinically significant angiographic lesions was moderate.

PMID- 22150845
TI  - Facial symmetry in robust anthropometrics.
AB  - Image analysis methods commonly used in forensic anthropology do not have
      desirable robustness properties, which can be ensured by robust statistical
      methods. In this paper, the face localization in images is carried out by
      detecting symmetric areas in the images. Symmetry is measured between two
      neighboring rectangular areas in the images using a new robust correlation
      coefficient, which down-weights regions in the face violating the symmetry. Raw
      images of faces without usual preliminary transformations are considered. The
      robust correlation coefficient based on the least weighted squares regression
      yields very promising results also in the localization of such faces, which are
      not entirely symmetric. Standard methods of statistical machine learning are
      applied for comparison. The robust correlation analysis can be applicable to
      other problems of forensic anthropology.

PMID- 22150846
TI  - Bilateral motor cortex stimulation for the relief of central dysesthetic pain and
      intentional tremor secondary to spinal cord surgery: a case report.
AB  - Objectives. Our objective was to describe and analyze through a third party
      disinterested observer the results obtained by using motor cortex stimulation
      (MCS) for the treatment of central dysesthetic diffuse-distal type of paraplegic
      pain and intentional tremor secondary to the total removal of a cervical
      ependymoma. Design. Retrospective case report with discussion. Methods. A 69-year
      old female, who after satisfactory removal of a cervical ependymoma, developed a
      central dysesthetic diffuse-distal type of paraplegic pain and intentional tremor
      associated with mild cerebellar deficit. Neurologic compromise became so intense
      that it prevented the patient from leading an independent lifestyle. Conservative
      treatments failed and a unilateral trial of MCS was performed. After a four-day
      satisfactory unilateral trial, a bilateral electrode, Resume II (Medtronic, Inc.,
      Minneapolis, MN), was inserted through a small craniotomy and a dual-channel RF
      activated receiver was implanted. During the second month of follow-up an
      independent observer personally interviewed the patient and assessed results
      through a multimodal approach, encompassing several analog scales used to measure
      the different components of the painful experience; a daily life activities scale
      and drug intake. Results. Evoked painful phenomena were dramatically improved,
      but the steady component of pain was only moderately relieved. The patient's
      tremor improved to allow for the performance of simple movements such as
      independent eating. Conclusion. In this single case report MCS was extremely
      useful in eliminating almost all of the patient's pain-evoked phenomena. Both
      steady burning pain and tremor were also improved. This is only one case report
      and MCS warrants further investigation as to its utility in controlling central
      dysesthetic pain in paraplegia and postchordotomy dysesthesias.

PMID- 22150847
TI  - Intrathecal bupivacaine for chronic pain: a review of current knowledge.
AB  - Objective. This article presents an overview of the use of intrathecal
      bupivacaine (with and without opioid), focusing on laboratory data and clinical
      use for chronic pain. Some background on epidural use is included to support the
      intrathecal literature. Materials and Methods. Currently available literature
      (MEDLINE) regarding the use of intrathecal bupivacaine is reviewed. Prior to
      presenting the intrathecal bupivacaine data, an overview of data related to
      bupivacaine stability, microbiology, preclinical toxicology, and pharmacokinetics
      is presented, along with a brief review of the epidural bupivacaine literature.
      Results. Based on the current available literature, intrathecal bupivacaine
      appears to be a safe and acceptable method of treatment for chronic pain in both
      cancer and noncancer patients. The stability and bacteriologic studies support
      the use of bupivacaine in external or implantable drug administration devices.
      Toxicity studies in laboratory animals suggest complications only at plasma
      levels that would not be seen at clinically relevant doses of intrathecal
      administration. Bupivacaine is a clinically effective addition to intrathecal
      opioids. Bupivacaine administration is more effective intrathecally, providing
      better pain relief than epidural administration. Reports of complications are
      infrequent. Further studies are needed to define the use of intrathecal
      bupivacaine and should include long-term safety. Compatibility studies will also
      be needed when bupivacaine is used in combination with other agents. In addition,
      outcome studies are needed specifically to differentiate use of intrathecal
      bupivacaine based on the source and mechanism of pain. Conclusions. While there
      are few long-term randomized prospective studies at this point, we conclude that
      intrathecal bupivacaine appears to be a safe and efficacious treatment in both
      cancer and noncancer pain.

PMID- 22150848
TI  - Efficacy and Safety of Intrathecal Opioid/Bupivacaine Mixture in Chronic
      Nonmalignant Pain: A Double Blind, Randomized, Crossover, Multicenter Study by
      the National Forum of Independent Pain Clinicians (NFIPC).
AB  - Objective. Intrathecal opioid/local anesthetic mixtures are a popular alternative
      in contemporary treatment of chronic nonmalignant pain. Unfortunately, its use is
      based solely on retrospective studies or anecdotal reports. Materials and
      Methods. A double blind, randomized, crossover, multicenter study was performed
      in 24 patients with intrathecal pumps. For four consecutive months, their pumps
      were refilled with either the original opioid or its mixture with different
      concentrations of bupivacaine(4, 6, or 8 mg/day). Results. Only one patient
      experienced mild side effects from intrathecal bupivacaine. A strong placebo
      response was observed in all patients when they entered the study. Addition of
      bupivacaine to the intrathecal opioid failed to produce significant improvement
      in pain control. Conclusion. At currently used doses, intrathecal opioid
      bupivacaine mixtures are not more efficacious in the treatment of chronic
      nonmalignant pain than opioid alone.

PMID- 22150849
TI  - The analgesic effects of intrathecally pumped saline and artificial cerebrospinal
      fluid in a rat model of neuropathic pain.
AB  - Objective. This experiment was performed to test the hypothesis that
      intrathecally pumped saline, but not artificial cerebrospinal fluid (CSF), would
      be analgesic in a rat model of neuropathic pain. Materials and Methods. Surgery
      for the chronic constriction injury (CCI) model of neuropathic pain and
      intrathecal catheter placement were performed on the rats, baseline pain testing
      and pump implantation were performed 7 days later, and pain tests were repeated
      on days 1, 4, 7, and 14 after pump implantation. Results. Intrathecally pumped
      saline and artificial CSF were analgesic for cold allodynia (p < 0.05), and
      intrathecally pumped saline but not CSF for heat nociception in the affected paw
      (p < 0.005) compared to rats with unattached subcutaneous pumps. No analgesia was
      observed on tests of spontaneous pain or pressure hyperalgesia (p > 0.1).
      Conclusions. Intrathecally pumped saline and artificial CSF have analgesic
      effects on some neuropathic and normal, nociceptive pain signs in CCI rats.

PMID- 22150850
TI  - Vocalization responses after spinal administration of bicuculline or strychnine
      in rats.
AB  - Objective. Spinal administration of compounds decreasing inhibition of spinal
      nociceptive pathways, such as antagonists of GABA or glycine receptors, leads to
      vocalization. This can be quantified semiautomatically and could be used as a
      research model. Materials and Methods. Vocalization after intrathecal
      administration of bicuculline and strychnine was measured in Sprague-Dawley rats.
      Results. Both bicuculline and strychnine produced short, dose-related
      vocalization responses that were not significantly different between models of
      peripheral inflammation and neuropathic pain and normal controls, except for
      reduced strychnine-induced vocalization during inflammation. The strychnine
      induced vocalization responses were also reduced in freely moving rats and
      increased by light tactile stimulation. Conclusions. Bicuculline-induced
      vocalization seems to be related to facilitation of nociceptive transmission, and
      could have limited use as a model of nociception at the spinal level. However,
      peripheral inflammation or neuropathic pain did not affect it. Strychnine-induced
      vocalization responses seem to be related to non-noxious somatosensory input.

PMID- 22150851
TI  - Effects of Transcutaneous Electrical Nerve Stimulation (TENS) Electrode Placement
      on Spontaneous and Noxiously Evoked Dorsal Horn Cell Activity in the Cat.
AB  - The objectives of this study were to examine the effects of ipsilateral vs.
      contralateral as well as simultaneous placement of transcutaneous electrical
      nerve stimulation (TENS) electrodes in somatic receptive fields on spontaneous
      and noxiously evoked dorsal horn cell activity in anesthetized cats. Recordings
      were made from cells in the left gray matter of lumbosacral segments. In this
      study ipsilateral means left and contralateral means right. Results showed that
      mean cell activity decreased significantly (p < 0.001) when electrodes were
      placed in somatic receptive fields of either the contralateral (right) or
      ipsilateral (left) lower extremity. When comparing contralateral vs. ipsilateral
      effects, the most significant reduction (p < 0.004) in mean cell activity
      occurred with ipsilateral (left) placement of the electrodes. For bilateral
      application (simultaneous ipsilateral and contralateral) of TENS electrodes, 66%
      of the cells demonstrated a significant additive effect in reducing spontaneous
      and noxiously evoked cell activity. Clinically, the results might suggest that
      analgesia can result from bilateral placement of electrodes or by placement of
      electrodes in the contralateral dermatome (somatic field) when certain clinical
      conditions may prevent the placement of electrodes on the same side (ipsilateral)
      as the perceived pain.

PMID- 22150852
TI  - An integrated implantable electrical sacral root stimulator for bladder control.
AB  - Objectives. The goal of this work is to study and develop an electrical
      integrated system that allows the control of the basic functions (such as
      micturition, defecation, and erection) by sacral root stimulation in paraplegic
      patients. Materials and Methods. The system has been implemented using a
      commercially available Mietec CMOS technology. It is based on an external
      transceiver unit, which provides data and energy to the implant device through a
      bi-directional inductive link, and an implantable batteryless module that
      generates the needed current pulses, according to the orders received from the
      external unit. To test the electrode-tissue interface and system performance, an
      impedance measurement circuit has been included. Results. The three independent
      channel stimulators allow an exhaustive control of the waveform parameters
      (amplitude, pulse width, frequency) independent of the placement of the external
      coil respect to the internal device. Conclusion. The architecture of the new
      stimulator, applied over the sacral roots, can be used to control the voiding of
      the bladder. The system allows an independent distance programmable stimulation.
      The impedance measurement circuit implemented allows an easy and systematic
      performance test.

PMID- 22150853
TI  - Automatic Finite State Control of FES-Assisted Indoor Rowing Exercise after
      Spinal Cord Injury.
AB  - We modified a commercial indoor rowing machine (Concept 2 Inc., Morrisville, NJ,
      USA) for a functional electrical stimulation (FES) assisted indoor rowing
      exercise in which the rowers must repeatedly press the two switches on the handle
      that stimulate their paralyzed leg muscles. The objective of this study was to
      automate the delivery of electrical stimulation to prevent potential repetitive
      strain injuries and to expand the user base to clients with impaired hand
      function. The modifications for development of the FES rowing machine and
      clinical trials were all performed in the University of Alberta. A new controller
      was developed to automatically control the electrical stimulation of the
      paralyzed leg muscles to perform the lower extremity part of the rowing maneuver
      while the subject voluntarily performed the upper body part of the maneuver. Two
      paraplegic users of the older manual control system tested the new automatic
      controller. The automatic FES controller spent more electrical stimulation per
      rowing cycle but it did not require repetitive thumb presses, required less
      concentration, and was preferred by the clients. We conclude FES rowing with the
      new automatic controller was easier and safer and expanded the user base of the
      FES rowing exercise to those with affected hand.

PMID- 22150854
TI  - Enhancement of isometric ankle dorsiflexion by automyoelectrically controlled
      functional electrical stimulation on subjects with upper motor neuron lesions.
AB  - The objective of this study was to test myoelectrically controlled functional
      electrical stimulation of the same muscle (AutoMCS) on patients with either
      stroke or spinal cord injury. The paretic anterior tibialis (TA) muscle was
      stimulated with an amplitude controlled continuously by the volitional
      myoelectric signal from the same muscle. Surface electrodes were used and
      volitional myoelectric signals were extracted by analog/digital signal processing
      techniques. Isometric dorsiflexion torque of the foot was displayed on a screen
      and the subjects were asked to track a sinusoidal curve. Subjects with dropped
      foot, as a result of a stroke (CVA, n = 9) or spinal cord lesion (SCI, n = 4),
      performed tests without and then with AutoMCS applied to the muscle. Subjects
      were their own control and tracking tests without and with AutoMCS. Changes in
      torque range, tracking delay, and tracking control accuracy have been evaluated.
      A significant (p < 0.05) increase of dorsiflexion torque by AutoMCS was found. An
      immediate carryover effect was seen in one stroke subject. The analysis of the
      tracking control showed only little loss of controllability with the system. We
      conclude that for selected subjects this method can instantly increase the muscle
      force of the anterior tibialis without significantly compromising tracking
      control or tracking delay.

PMID- 22150855
TI  - Erratum.

PMID- 22150858
TI  - Contents to volume 5.

PMID- 22150860
TI  - Comparison of blood samples values by direct venipuncture and central venous
      catheters with 5 or 10 ml wasted blood.

PMID- 22150861
TI  - Story-sharing as a method of data collection in qualitative research.

PMID- 22150862
TI  - Commentary on Lin LC, Li MH & Watson R (2011) A survey of the reasons patients do
      not choose percutaneous endoscopic gastrostomy/jejunostomy (PEG/PEJ) as a route
      for long-term feeding. Journal of Clinical Nursing 20, 802-810.

PMID- 22150863
TI  - Commentary on Lin PC, Lin ML, Huang LC, Hsu HC & Lin CC (2011) Music therapy for
      patients receiving spine surgery. Journal of Clinical Nursing 20, 960-968.

PMID- 22150864
TI  - Commentary on Jelsness-Jorgensen L-P, Ribu L, Bernklev T & Moum BA (2011)
      Measuring health-related quality of life in non-complicated diabetes patients may
      be an effective parameter to assess patients at risk of a more serious disease
      course: a cross-sectional study of two diabetes outpatient groups. Journal of
      Clinical Nursing 20, 1255-1263.

PMID- 22150865
TI  - Response to Watson R (2011) Commentary on Oermann MH, Shaw-Kokot J, Knafl GJ &
      Dowell J (2010) Dissemination of research into clinical nursing literature.
      Journal of Clinical Nursing 19, 3435-3442. Journal of Clinical Nursing 20, 595
      596.

PMID- 22150866
TI  - Response to Henderson (2011) Commentary on Williamson GR, Callaghan L, Whittlesea
      E & Heath V (2011) Improving student support using placement development teams:
      staff and student perceptions. Journal of Clinical Nursing 20, 1502-1503.

PMID- 22150867
TI  - Response to Commentary on Watt E, Murphy M, Pascoe E, Scanlon A & Gan S (2011) An
      evaluation of a structured learning programme as a component of the clinical
      practicum in final year bachelor of nursing programme: a pre-post test analysis.
      Journal of Clinical Nursing 20, 2286-2293.

PMID- 22150868
TI  - Asymmetric and differential gene introgression at a contact zone between two
      highly divergent lineages of field voles (Microtus agrestis).
AB  - Secondary contact zones have the potential to shed light on the mode and rate at
      which reproductive isolation accumulates during allopatric speciation. We
      investigated the population genetics of a contact zone between two highly
      divergent lineages of field voles (Microtus agrestis) in the Swiss Jura
      mountains. To shed light on the processes underlying introgression, we used
      maternally, paternally, and bi-parentally inherited markers. Though the two
      lineages maintained a strong genetic structure, we found some hybrids and
      evidence of gene flow. The extent of introgression varied with the mode of
      inheritance, being highest for mtDNA and absent for the Y chromosome. In
      addition, introgression was asymmetric, occurring only from the Northern to the
      Southern lineage. Both patterns seem parsimoniously explained by neutral
      processes linked to differences in effective sizes and sex-biased dispersal
      rates. The lineage with lower effective population size was also the more
      introgressed, and the mode-of-inheritance effect correlated with the male-biased
      dispersal rate of microtine rodents. We cannot exclude, however, that Haldane's
      effect contributed to the latter, as we found a marginally significant deficit in
      males (the heterogametic sex) among hybrids. We propose a possible demographic
      scenario to account for the patterns documented, and empirical extensions to
      further investigate this contact zone.

PMID- 22150869
TI  - External ultrasonography of the neck does not add diagnostic value to integrated
      positron emission tomography-computed tomography (PET-CT) scanning in the
      diagnosis of cervical lymph node metastases in patients with esophageal
      carcinoma.
AB  - One of the objectives of preoperative imaging in esophageal cancer patients is
      the detection of cervical lymph node metastases. Traditionally, external
      ultrasonography of the neck has been combined with computed tomography (CT) in
      order to improve the detection of cervical metastases. In general, integrated
      positron emission tomography-computed tomography (PET-CT) has been shown to be
      superior to CT or PET regarding staging and therefore may limit the role of
      external ultrasonography of the neck. The objective of this study was to
      determine the additional value of external ultrasonography of the neck to PET-CT.
      This study included all patients referred our center for treatment of esophageal
      carcinoma. Diagnostic staging was performed to determine treatment plan. Cervical
      lymph nodes were evaluated by external ultrasonography of the neck and PET-CT. In
      case of suspect lymph nodes on external ultrasonography or PET-CT, fine needle
      aspiration (FNA) was performed. Between 2008 and 2010, 170 out of 195 referred
      patients underwent both external ultrasonography of the neck and PET-CT. Of all
      patients, 84% were diagnosed with a tumor at or below the distal esophagus. In
      140 of 170 patients, the cervical region was not suspect; no FNA was performed.
      Seven out of 170 patients had suspect nodes on both PET-CT and external
      ultrasonography. Five out of seven patients had cytologically confirmed malignant
      lymph nodes, one of seven had benign nodes, in one patient FNA was not performed;
      exclusion from esophagectomy was based on intra-abdominal metastases. In one out
      of 170 patients, PET-CT showed suspect nodes combined with a negative external
      ultrasonography; cytology of these nodes was benign. Twenty-two out of 170
      patients had a negative PET-CT with suspect nodes on external ultrasonography. In
      18 of 22 patients, cervical lymph nodes were cytologically confirmed benign; in
      four patients, FNA was not possible or inconclusive. At a median postoperative
      follow-up of 15 months, only 1% of patients developed cervical lymph node
      metastases. This study shows no additional value of external ultrasonography to a
      negative PET-CT. According to our results, it can be omitted in the primary
      workup. However, suspect lymph nodes on PET-CT should be confirmed by FNA to
      exclude false positives if it would change treatment plan.

PMID- 22150870
TI  - Association between serum 25-hydroxyvitamin D in early pregnancy and risk of
      gestational diabetes mellitus.
AB  - AIMS: There is emerging evidence of a relationship between vitamin D
      insufficiency and glucose intolerance. The aim of this study was to determine
      whether low serum 25-hydroxyvitamin D in early pregnancy is associated with an
      increased risk of gestational diabetes mellitus. METHODS: This nested case
      control study examined the association between serum 25-hydroxyvitamin D and risk
      of gestational diabetes within a cohort of pregnant women from March 2008 to
      December 2009, who had undergone antenatal screening between 15 and 18 weeks
      gestation and subsequent glucose tolerance testing. Cases were women diagnosed
      with gestational diabetes and each case was matched to up to two controls without
      gestational diabetes on age, race and date of blood collection. Serum 25
      hydroxyvitamin D was measured from stored antenatal screening samples and
      compared between cases and controls. RESULTS: Of the 116 women with gestational
      diabetes and 219 control subjects studied, the average age was 34.3 years and 41%
      were of non-Caucasian race. Women with gestational diabetes had significantly
      lower serum 25-hydroxyvitamin D compared with control subjects (56.3 vs. 62.0
      nmol/l, P = 0.018). After adjusting for gestational age and maternal weight,
      serum 25-hydroxyvitamin D below the top quartile (< 73.5 nmol/l) was associated
      with a twofold greater likelihood of gestational diabetes (adjusted odds ratio
      2.21, 95% confidence interval 1.19-4.13). CONCLUSIONS: Lower vitamin D status in
      early pregnancy was associated with a significantly increased risk of subsequent
      gestational diabetes that was independent of race, age, season and maternal
      weight. This study suggests that vitamin D may influence glucose tolerance during
      pregnancy and provides support for studies of vitamin D as a potential
      intervention to prevent gestational diabetes.

PMID- 22150871
TI  - Different guidelines for different countries? On the scientific basis of low-risk
      drinking guidelines and their implications.
AB  - The scientific evidence for low-risk drinking guidelines was examined in a
      narrative review focusing on three points: definition of exposure, the best way
      to select outcomes and risk relations and how to determine thresholds. With
      respect to exposure, at least two dimensions should be incorporated: average
      volume of alcohol consumption and patterns of irregular heavy drinking occasions.
      Mortality should be selected as the most severe outcome, and a disaggregated
      approach should be adopted incorporating the regional demographic and cause of
      death structure. Finally, our plea is for establishing a general threshold for
      acceptable risk on a societal level rather than ad hoc specific committees
      setting norms for specific risks. Acceptable thresholds will be different if the
      risk is to oneself or to others.

PMID- 22150874
TI  - Overlap of dyspepsia and gastroesophageal reflux in the general population: one
      disease or distinct entities?
AB  - BACKGROUND: The overlap of dyspepsia and gastroesophageal reflux (GER) is known
      to be frequent, but whether the overlap group is a distinct entity or not remains
      unclear. The aims of the study was to evaluate whether the overlap of dyspepsia
      and GER (dyspepsia-GER overlap) occurs more than expected due to chance alone,
      and evaluate the risk factors for dyspepsia-GER overlap. METHODS: In 2008 and
      2009, a validated Bowel Disease Questionnaire was mailed to a total of 8006
      community sample from Olmsted County, MN. Overall, 3831 of the 8006 subjects
      returned surveys (response rate 48%). Dyspepsia was defined by symptom criteria
      of Rome III; GER was defined by weekly or more frequent heartburn and/or acid
      regurgitation. KEY RESULTS: Dyspepsia and GER occurred together more commonly
      than expected by chance. The somatic symptom checklist score was significantly
      associated with dyspepsia-GER overlap vs GER alone or dyspepsia alone [OR = 1.9
      (1.4, 2.5), and 1.6 (1.2, 2.1), respectively]. Insomnia was also significantly
      associated with dyspepsia-GER overlap vs. GER alone or dyspepsia alone [OR = 1.4
      (1.1, 1.7), OR = 1.3 (1.1, 1.6), respectively]. Moreover, proton pump inhibitor
      use was significantly associated with dyspepsia-GER overlap vs dyspepsia alone
      [OR = 2.4 (1.5, 3.8)]. CONCLUSIONS & INFERENCES: Dyspepsia-GER overlap is common
      in the population and is greater than expected by chance.

PMID- 22150875
TI  - Relative prevalence of upper respiratory tract obstructive disorders in two
      breeds of harness racehorses (185 cases: 1998-2006).
AB  - REASONS FOR PERFORMING STUDY: Two genetically and phenotypically distinct horse
      breeds are used for harness racing in Scandinavia: the Standardbred (SB) and
      Coldblooded Trotter. These racehorses have identical environmental, management
      and racing conditions. Therefore, this study was undertaken to identify and
      compare the relative prevalence of upper respiratory tract (URT) obstructive
      disorders in these 2 breeds. OBJECTIVES: To determine whether these 2
      phenotypically different breeds of harness racehorses have different
      predispositions for URT disorders. METHODS: Retrospective study of 88 Norwegian
      Coldblooded Trotters (NCT) and 97 SBs referred to this hospital for URT
      evaluation between 1998 and 2006. Case records of all horses diagnosed with an
      URT disorder during resting endoscopy, and all horses undergoing high-speed
      treadmill videoendoscopy (HSTV) with one or more periods of induced poll flexion
      were evaluated. The relative prevalence of URT disorders between the 2 breeds was
      analysed using a Fisher's exact test. RESULTS: There was a significant (P<0.05)
      breed predisposition regarding 6 URT disorders. Bilateral dynamic laryngeal
      collapse associated with poll flexion and flaccid epiglottis was significantly
      more frequent in the NCT. Alar fold collapse and nasopharyngeal collapse were
      significantly more frequent in SBs. Epiglottic entrapment and nasal flutter were
      only diagnosed in the SBs. Dynamic disorders were more common than resting
      disorders in both breeds. CONCLUSION: URT obstructive disorders (dynamic
      laryngeal collapse associated with poll flexion, flaccid epiglottis, pharyngeal
      collapse, alar fold collapse, nasal flutter and epiglottic entrapment) are breed
      related, indicating an anatomic or functional cause. Periods of induced poll
      flexion during HSTV was essential to declare harness racehorses free of URT
      disorders. POTENTIAL RELEVANCE: Further anatomic or physiological studies
      comparing these breeds could potentially provide insight into the pathogenesis of
      certain URT obstructive disorders. Induced poll flexion should be included in
      routine HSTV examinations of all harness racehorses.

PMID- 22150876
TI  - Clinical evaluation of a ridge augmentation procedure for the severely resorbed
      alveolar socket: multicenter randomized controlled trial, preliminary results.
AB  - OBJECTIVE: To radiographically analyze extraction sites left untreated or treated
      using a socket preservation technique. MATERIALS AND METHODS: A total of 20
      patients scheduled for single extraction in the maxilla from second to second
      premolar were enrolled in this study. All sites showed a bone defect >5 mm at the
      buccal wall and no soft tissue recession. At baseline (T0), tooth extraction was
      performed; subsequently, sites were randomly allocated to the control (CG: left
      to heal without grafting) or test group (TG: grafted using hydroxyapatite). Two
      months later (T1), implants were inserted and eventual GBR procedure was
      performed. Three months later, the definitive crown was placed. Follow up was 24
      months (T2). A cone-beam computed tomographic examination (CT) was performed at
      each time point. At each radiographic analysis, horizontal and vertical widths of
      the sockets were measured. Comparisons between CG and TG were performed by a
      Wilcoxon non-parametric test. RESULTS: At the end of the study, no patient
      dropped out and all implants inserted (10 in each group) resulted integrated. GBR
      procedures were performed at T1 only in the CG. In the CG, the mean value of the
      horizontal width in the coronal CT slices was 0.98 mm (+/- 0.37), 7.70 mm (+/-
      0.92), 7.45 mm (+/- 0.69) at T0, T1 (after bone regeneration) and T2,
      respectively. In the TG, the mean value of the horizontal width in the coronal CT
      slices was 0.96 mm (+/- 0.41), 8.97 mm (+/- 1.91), 9.48 mm (+/- 1.56); at T2, it
      was 9.52 mm (+/- 1.87) at T0 (pre- and post-socket preservation) T1 and T2,
      respectively. At each follow up, the mean horizontal bone width in TG was
      statistically significantly greater than in the control group (P < 0.05). At T0,
      mean value of the vertical bone defect length (BDL) was 6.93 mm for TG, 6.5 mm
      for CG. At T1 and T2, mean BDL value was 0 for both groups. Statistically
      significant difference was not found between TC and CG at any time point (P >
      0.05). CONCLUSIONS: This randomized controlled trial suggested that in sites with
      buccal bone defects >5 mm, the application of HA can minimize alveolar crest
      resorption following tooth extraction. Furthermore, compared with traditional
      regenerative procedure carried out following socket healing, this preservation
      technique seems to result in better horizontal regeneration of the buccal bone
      wall.

PMID- 22150877
TI  - Sulfoquinovose degraded by pure cultures of bacteria with release of C3
      organosulfonates: complete degradation in two-member communities.
AB  - Sulfoquinovose (SQ, 6-deoxy-6-sulfoglucose) was synthesized chemically. An HPLC
      ELSD method to separate SQ and other chromophore-free sulfonates, e.g. 2,3
      dihydroxypropane-1-sulfonate (DHPS), was developed. A set of 10 genome-sequenced,
      sulfonate-utilizing bacteria did not utilize SQ, but an isolate, Pseudomonas
      putida SQ1, from an enrichment culture did so. The molar growth yield with SQ was
      half of that with glucose, and 1 mol 3-sulfolactate (mol SQ)(-1)  was formed
      during growth. The 3-sulfolactate was degraded by the addition of Paracoccus
      pantotrophus NKNCYSA, and the sulfonate sulfur was recovered quantitatively as
      sulfate. Another isolate, Klebsiella oxytoca TauN1, could utilize SQ, forming 1
      mol DHPS (mol SQ)(-1) ; the molar growth yield with SQ was half of that with
      glucose. This DHPS could be degraded by Cupriavidus pinatubonensis JMP134, with
      quantitative recovery of the sulfonate sulfur as sulfate. We presume that SQ can
      be degraded by communities in the environment.

PMID- 22150879
TI  - Editor's Note.

PMID- 22150878
TI  - Evaluation of the supportive needs of adolescents during childbirth intrapartum
      nursing intervention on adolescents' childbirth satisfaction and breastfeeding
      rates.
AB  - OBJECTIVE: To evaluate the effect of the Supportive Needs of Adolescents during
      Childbirth (SNAC) intrapartum nursing intervention on adolescents' childbirth
      satisfaction and breastfeeding rates. DESIGN: Separate sample posttest quasi
      experimental. SETTING: A tertiary hospital intrapartum unit. PARTICIPANTS: A
      convenience sample of 106 parturient adolescents. METHODS: During Phase 1 the
      control group received current standard of intrapartum care. During Phase 2, the
      interventionist nurses provided the SNAC intervention and standard of care to the
      intervention group. RESULTS: The t test indicated higher childbirth satisfaction
      in the intervention group. Chi-square analysis indicated that the intervention
      group was more likely to breastfeed within the first hour after birth. There was
      no significant relationship between childbirth satisfaction and breastfeeding at
      three months and no differences between the groups in breastfeeding rates at
      hospital discharge and three months. CONCLUSIONS: These results suggest that
      learning the SNAC intervention may help nurses positively influence adolescents'
      childbirth experience and timing of breastfeeding initiation. Replication of the
      study is needed to further explore whether the intervention can significantly
      influence breastfeeding duration.

PMID- 22150880
TI  - Chronic Intrathecal Baclofen Administration for the Treatment of Severe
      Generalized Tetanus via a Synchromed Infusion Pump.
AB  - Centers for Disease Control (CDC) data indicate that the incidence of tetanus in
      the United States is highest among the elderly. Conventional therapies for the
      control of accompanying generalized muscle spasms include large doses of oral or
      intravenous GABA agonists as antispasticity agents. We describe a case of an
      elderly patient with severe symptoms of tetanus who developed a prolonged
      encephalopathy and ventilatory insufficiency with oral baclofen and
      benzodiazepine therapy. Intrathecal baclofen adequately controlled her severe
      extensor spasms, facilitated her ventilatory management, and did not compromise
      her mental status during her extended convalescence. Accordingly, we report the
      first placement of a permanent implanted infusion pump for this disease. This
      modality offers advantage for continuous long-term titration of medication for
      spasms or rigidity control without the systemic sedative effects of conventional
      therapy.

PMID- 22150881
TI  - Psychological variables associated with outcome of spinal cord stimulation
      trials.
AB  - Study Design. This is a prospective study designed to identify psychological
      factors associated with response to spinal cord stimulation (SCS) trial. Summary
      of Background Data. In most centers, implantation of a permanent SCS system is
      preceded by a trial of a temporary stimulating electrode. Yet, even among those
      who report greater than 50% pain reduction during trial, a significant number of
      these patients fail to receive long-term pain relief from the permanent system.
      Because mood disorders can alter pain report, we hypothesized that refined
      definition of the psychological factors associated with SCS success could result
      in improved selection of candidates for SCS trial. Methods. The study sample
      consisted of 43 chronic pain patients (72% failed back surgery syndrome, 77% with
      radiating low back pain) who were referred for implantable pain management.
      Following psychological evaluation, patients were admitted for a three-day
      inpatient trial of SCS. Report of at least 50% pain relief during trial was
      considered a success and resulted in implantation of the permanent stimulator.
      Patients were retrospectively divided into two groups: those whose pretrial pain
      was relieved by at least 50% ("success") and those whose pain was relieved by
      less than 50% ("failure"). Results. Univariate t-test or chi-square analyzes of
      group means of an extensive psychological battery followed by a global, stepwise
      logistic regression model of trial outcome was used to analyze between group
      results of a psychological test battery. MMPI depression and mania subscores were
      found to be significantly elevated among the two outcome groups (p = 0.007 and
      0.025, respectively). Conclusions. Patient mood state is an important predictor
      of trial outcome. Specific indicators of SCS trial outcome are the MMPI
      depression and mania subscale scores with successful trials being associated with
      individuals who are less depressed and have higher energy levels.

PMID- 22150882
TI  - Analysis of spinal cord stimulation and design of epidural electrodes by computer
      modeling.
AB  - This paper is an overview of the results of computer modeling of spinal cord
      stimulation, started ten years ago at the University of Twente, The Netherlands.
      Results are given of the analysis of various geometrical factors, including
      spinal anatomy, which influence the effect of spinal cord stimulation on nerve
      fiber recruitment and paresthesia coverage. In a second phase, the computer model
      was used for the design of new electrode configurations expected to give a better
      paresthesia coverage in the management of chronic pain. Two new electrode types
      are presented: the narrow bi-/tripole and the transverse tripole. The latter also
      enables adjusting the body area affected with paresthesia by means of a dual
      channel pulse generator giving simultaneous pulses, thereby limiting surgical
      interventions for electrode repositioning.

PMID- 22150883
TI  - Long-term outcome of spinal cord stimulation for chronic pain management.
AB  - Study Design. This is a retrospective study on 102 patients subjected to
      implantation of a spinal cord stimulation system for nonmalignant chronic pain
      management. The study was conducted through an extensive questionnaire and
      telephone interviews by a neutral third party. All the patients were implanted
      with a complete spinal cord stimulation system without a preliminary trial with a
      temporarily implanted electrode. Diagnostic categories were neuropathic pain,
      failed back syndrome, spinal cord Injury pain, and miscellaneous. Average follow
      up was 3.8 years (6 months to 8 years). Patients were divided in two groups: all
      the implanted patients in the survey (Group A) and the implanted patients who
      experienced some degree of pain relief with the stimulation (Group B). Group B
      (80 patients) closely matches previously published series where an initial
      temporary screening was performed. Results. Twenty-one percent of the patients
      never experienced any pain relief. Of the remaining 80, 75% were still using the
      stimulator. Fifty-one percent of the 80 patients were experiencing good to
      excellent results and 20% moderate results. There was no reduction over time in
      the amount of pain relief in patients who initially had at least 75% pain relief.
      Patients with initial pain relief between 50% and 74% observed a moderate
      reduction in their pain relief after two years. Patients who initially
      experienced less than 50% pain relief observed a dramatic reduction in their
      results in the long term follow-up. Psychological screening contributed to the
      success of the procedure. Conclusions. With proper medical and psychological
      screening and with demonstrated initial pain relief, spinal cord stimulation
      remains an effective modality in the long-term management of severe chronic pain.

PMID- 22150884
TI  - Computer assisted and patient interactive programming of dual octrode spinal cord
      stimulation in the treatment of chronic pain.
AB  - Objective. To evaluate the effectiveness of spinal cord stimulation using
      multiple independent programmable electrode selections compared to simple
      continuous stimulation. Design. Prospective case series 2 years. Setting.
      Ambulatory care center. Patients. All chronic pain patients who underwent spinal
      cord stimulation treatment at our center from February 1995 until October 1996
      entered the study as a consecutive sample (n = 80). Interventions. Patients were
      evaluated in continuous stimulation mode (single stimulation program) vs. multi
      stimulation mode, (patients activate a series of stimulation programs
      simultaneously to cover all of their pain) and patient-controlled stimulation
      mode (patients can select a program in response to their activities and pain
      level). Outcome measures. We collected visual analog pain scores, patient
      satisfaction scores by stimulation mode, and paresthesia maps. Results. Mean pain
      scores declined from 8.1 at baseline to 4.6 with continuous stimulation, and to
      3.1 with multi-stimulation and with patient-controlled stimulation (p<0.05).
      Paresthesia overlap improved from 74% with continuous stimulation to 91% with
      multi-stimulation, and to 89% with patient-controlled stimulation (p<0.05). None
      of the patients selected continuous stimulation. Thirty-two patients preferred
      multi-stimulation, and 48 patients preferred patient-controlled stimulation. Lead
      revision rates declined from 15% in our previous experience using continuous
      stimulation to 3.8%. Conclusions. Continuous stimulation was not selected by any
      patient in favor of multi-stimulation or patient-controlled stimulation. This
      study indicates that in spinal cord stimulation the use of multiple electrodes
      together with advanced programmability increases paresthesia overlap, reduces
      pain scores, reduces revision rates, and improves patient satisfaction with
      spinal cord stimulation therapy.

PMID- 22150885
TI  - Intraspinal analgesia for nonmalignant pain: a retrospective analysis for
      efficacy, safety and feasability in 50 patients.
AB  - Objectives. To test the efficacy and safety of intraspinal opioids for patients
      with nonmalignant pain. Design. A retrospective analysis on 50 patients, 37
      females and 13 males, who prior to intraspinal analgesia failed all conventional
      therapies including strong oral opioid trials. Patients were divided into three
      groups according to pain type: neuropathic, nociceptive, mixed
      neuropathic/nociceptive. Morphine equivalent doses were noted at intervals of 1,
      2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 months. Global evaluation of pain
      relief (poor, fair, good, excellent) was obtained at each return visit. Dose
      requirements, escalations, and decreases were noted and analyzed. Side effects
      and complications of drug infusion or mechanical devises were noted and
      tabulated. Results. 7 of 7 patients with nociceptive pain had good (29%) to
      excellent (71%) pain relief. Sixty percent of the 16 patients with neuropathic
      pain had good (47%) to excellent (13%) pain relief. Seventy-two percent of the
      total of patients with mixed pain had good (40%) to excellent (32%) pain relief.
      When further subdivided, only 59% of the failed back/arachnoiditis sufferers had
      good (41%) to excellent (18%) pain relief while 100% of the mixed group with non
      FBSS diagnoses had good (37%) to excellent (63%) pain relief. Conclusions. Long
      term intrathecal opioids are efficacious, practical, and safe for the treatment
      of nonmalignant pain syndromes. FBSS patients respond similarly to intraspinal
      analgesia as the patients with neuropathic pain, while the group with mixed pain
      from other non-FBSS causes respond similarly to the nociceptive pain patients.

PMID- 22150886
TI  - Pneumonia in allogeneic stem cell transplantation recipients: a multicenter
      prospective study.
AB  - Pneumonia is a common cause of mortality after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) but updated and prospective information is partial.
      The aim of this nationwide prospective study is to determine the current
      epidemiology, etiology, and outcome of pneumonia in allo-HSCT recipients. From
      September-2003 to November-2005, 112 episodes in 427 consecutive allo-HSCT
      recipients were included (incidence 52.2 per 100 allo-HSCT/yr), and 72 of them
      (64.3%) were microbiologically defined pneumonia. Bacterial pneumonia (44.4%) was
      more frequent than fungal (29.2%) and viral pneumonia (19.4%). The most frequent
      microorganisms in each group were: Escherichia coli (n = 7, 8.9%), Streptococcus
      pneumoniae (n = 4, 5.0%), cytomegalovirus (n = 12, 15.4%), and Aspergillus spp.
      (n = 12, 15.4%). The development of pneumonia and chronic graft-versus-host
      disease (GVHD) was associated with increased mortality after allo-HSCT, and the
      probability of survival was significantly lower in patients that had at least one
      pneumonia episode (p < 0.01). Pneumonia development in the first 100 d after
      transplantation, fungal etiology, GVHD, acute respiratory failure, and septic
      shock were associated with increased mortality after pneumonia. Our results show
      that pneumonia remains a frequent infectious complication after allo-HSCT,
      contributing to significant mortality, and provide a large current experience
      with the incidence, etiology and outcome of pneumonia in these patients.

PMID- 22150887
TI  - The multidrug-resistant bacteria attitude questionnaire: validity and
      understanding of responsibility for infection control in Swedish registered
      district, haematology and infection nurses.
AB  - AIM: To assess the discriminative and construct validity of the Multidrug
      Resistant Bacteria Attitude Questionnaire and to study registered nurses'
      knowledge of, behaviour toward and emotional responses to patients with multidrug
      resistant bacteria in relation to how they understand their own, managers' and
      politicians' responsibility for adherence to preventive measures for infection
      control. BACKGROUND: Multidrug-resistant organisms are a global problem and an
      essential topic in healthcare regarding patient safety improvement. DESIGN:
      Descriptive and correlational cross-sectional survey. METHOD: Data were collected
      in a non-random sample consisting of 397 registered nurses; district, haematology
      or infection registered nurses. One-way analysis of variance and independent t
      tests were used for comparisons and a principal component analysis was performed.
      RESULTS: Discriminative and construct validity were supported, as the infection
      registered nurses generally had higher scores on knowledge, behaviour and
      emotional response, compared with district registered nurses and haematology
      registered nurses and the three-factor solution was confirmed. Registered nurses
      with higher scores on knowledge and emotional response attributed greater
      responsibility to themselves and to politicians. The Multidrug-Resistant Bacteria
      Attitude Questionnaire was translated using a forward-back translation process.
      CONCLUSION: The questionnaire has adequate psychometric properties. Insufficient
      knowledge of, behaviour toward and emotional response to patients with multidrug
      resistant bacteria were described, but the registered nurses did estimate their
      own responsibility for adherence to preventive measures for infection control as
      being great or very great. RELEVANCE TO CLINICAL PRACTICE: There is a
      considerable need to improve knowledge, behaviour and emotional response
      regarding infection prevention measures among healthcare workers. The hospital
      management are responsible for such improvements and the Multidrug-Resistant
      Bacteria Attitude Questionnaire is useful in identifying such needs, as it has
      adequate psychometric properties and is able to discriminate between groups.
      Evaluation among healthcare workers may indicate where to situate additional
      training, as this is of clinical significance for safe care.

PMID- 22150888
TI  - Right-to-left atrial shunting with normal intracardiac pressures following
      cardiac surgery: pathophysiology and management.
AB  - We present a case of acute respiratory insufficiency with right-to-left atrial
      shunting under normal intracardiac pressures discovered several days after aortic
      surgery for aortic dissection. We discuss the possible mechanisms and management
      of right-to-left atrial shunting through an atrial septum defect with normal
      intracardiac pressures following cardiac surgery.

PMID- 22150889
TI  - Informed consent revoked.

PMID- 22150891
TI  - A patient revoking consent during awake craniotomy: an ethical challenge.
AB  - Purpose.  The ethical challenges posed when a patient requests the
      discontinuation of a procedure during awake neurosurgeries are seldom discussed.
      We present such a case with a very brief ethics discussion. Case.  A patient with
      idiopathic parkinsonism requested the discontinuation of a surgery in the middle
      of the implantation of bilateral deep brain stimulator electrodes. In
      consultation with a clinical bioethicist and the patient's family, the surgical
      team decided that the patient's current wishes needed to be respected.
      Subsequently, the surgical team performed the steps necessary to safely halt the
      surgery. Conclusion.  Even though the patient had the privilege of requesting a
      discontinuation, the surgeon had an obligation to keep the patient safe.
      Processes should be in place to assist decision-making about the continuation of
      awake surgery after such a patient request.

PMID- 22150890
TI  - Polyanalgesic consensus conference 2007: recommendations for the management of
      pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary
      expert panel.
AB  - Background.  Expert panels of physicians and nonphysicians in the field of
      intrathecal therapies convened in 2000 and 2003 to make recommendations for the
      rational use of intrathecal analgesics based on the preclinical and clinical
      literature known up to those times. An expert panel of physicians convened in
      2007 to update previous recommendations and to form guidelines for the rational
      use of intrathecal opioid and nonopioid agents. Methods.  A review of preclinical
      and clinical published relevant studies from 2000 to 2006 was undertaken and
      disseminated to a convened expert panel of physicians and nonphysicians. Focused
      discussions were held on the rational use of intrathecal agents and a survey
      asking questions regarding intrathecal therapies management was given to the
      panelists. Results.  The panelists, after review of the literature from 2000 to
      2006 and discussion, created an updated algorithm for the rational use of
      intrathecal opioid and nonopioid agents in patients with nonmalignant and end-of
      life pain. Of note is that the panelists felt that ziconotide, based on new and
      relevant literature and experience, should be updated to a line one intrathecal
      drug.

PMID- 22150892
TI  - Transcranial magnetic stimulation in neurology: what we have learned from
      randomized controlled studies.
AB  - Background.  Initially developed to excite peripheral nerves, magnetic
      stimulation was quickly recognized as a valuable tool to noninvasively activate
      the cerebral cortex. The subsequent discovery that repetitive transcranial
      magnetic stimulation (rTMS) could have long-lasting effects on cortical
      excitability spawned a broad interest in the use of this technique as a new
      therapeutic method in a variety of neuropsychiatric disorders. Although the
      current outcomes from initial trials include some conflicting results, initial
      evidence supports that rTMS might have a therapeutic value in different
      neurologic conditions. Methods.  We reviewed the results of clinical trials of
      rTMS on four different disorders: stroke, Parkinson's disease, chronic refractory
      pain, and epilepsy. We reviewed randomized, controlled studies only in order to
      obtain the strongest evidence for the clinical effects of rTMS. Results.  An
      extensive literature review revealed 32 articles that met our criteria. From
      these studies, we found evidence for the therapeutic efficacy of rTMS,
      particularly in the relief of chronic pain and motor neurorehabilitation in
      single hemisphere stroke patients. Repetitive TMS also seems to have a
      therapeutic effect on motor function in Parkinson's disease, but the evidence is
      somewhat confounded by the uncontrolled variability of multiple factors. Lastly,
      only two randomized, sham-controlled studies have been performed for epilepsy;
      although evidence indicates rTMS may reduce seizure frequency in patients with
      neocortical foci, more research is needed to confirm these initial findings.
      Conclusions.  There is mounting evidence for the efficacy of rTMS in the short
      term treatment of certain neurologic conditions. More long-term research is
      needed in order to properly evaluate the effects of this method in a clinical
      setting.

PMID- 22150893
TI  - Long-term effects of electrical neurostimulation in patients with unstable
      angina: refractory to conventional therapies.
AB  - Background.  Patients with unstable angina pectoris may become refractory to
      conventional therapies. Electrical neurostimulation with transcutaneous
      electrical stimulation and/or spinal cord stimulation has been shown to be
      effective for patients with refractory unstable angina pectoris in hospital
      settings. Our aim was to investigate the effects of electrical neurostimulation
      on outcomes of unstable angina after hospital discharge, in terms of hospital re
      admission rates and long-term survival analysis. Method.  Twenty-seven
      consecutive patients with unstable angina pectoris, refractory to conventional
      therapies, received electrical neurostimulation in a tertiary referral hospital.
      We studied the number of hospital admissions in the year before when compared to
      the first year after electrical neurostimulation and performed survival analysis
      of the group. Results.  Twenty-six patients had beneficial effects of electrical
      neurostimulation during their admission to the hospital. During a mean follow-up
      of 6.6 +/- 4.1 years, electrical neurostimulation was still effective in 21 out
      of 26. In 11 patients with previous hospital admissions, the number of hospital
      admissions decreased significantly after electrical neurostimulation (p = 0.007).
      The combined mortality and (re)infarction rate after one-year follow-up was 14%.
      Conclusion.  The results of this observational study show long-term beneficial
      effects of electrical neurostimulation in a population of patients with unstable
      refractory angina. Therefore, electrical neurostimulation should be considered as
      a beneficial treatment for patients with unstable angina pectoris, refractory to
      conventional therapies.

PMID- 22150894
TI  - Spinal cord stimulation with interleaved pulses: a randomized, controlled trial.
AB  - Objectives.  The development of multicontact electrodes and programmable,
      implanted pulse generators has increased the therapeutic success of spinal cord
      stimulation (SCS) by enhancing the ability to capture and maintain
      pain/paresthesia overlap. This study sought to determine if interleaved
      stimulation and/or frequency doubling improves pain/paresthesia overlap in
      patients with failed back surgery syndrome. Methods.  Using a patient-interactive
      computer system that quantifies SCS performance and presents stimulation settings
      in randomized, double-blind fashion, we compared the effect on pain/paresthesia
      overlap of interleaved stimulation (rapidly interleaved pulse trains using two
      different contact combinations) vs. standard treatment with a single contact
      combination, controlling for frequency doubling. Stimulation amplitude (charge
      per phase, as determined by varying pulse voltage or width) was adjusted to a
      subjectively comfortable intensity (usage amplitude), which was maintained for
      all trials in each patient. The number of percutaneous spinal electrodes used
      (one or two) and the phase angle between interleaved pulses were additional study
      variables. Results.  Multivariate analysis of 266 test results from 15 patients
      revealed a statistically significant (p <= 0.05) association between increased
      computer-calculated pain/paresthesia overlap and 1) high- and low-frequency
      interleaved stimulation using two combinations of contacts and 2) frequency
      doubling using one combination. We found no significant effect for electrode
      configuration (single or dual), pulse width matching, or phase angle.
      Conclusions.  The statistically significant advantages we observed for SCS with
      interleaved stimulation are explained, at least in part, by the effects of
      frequency doubling. These findings have important implications for the design and
      adjustment of pulse generators.

PMID- 22150895
TI  - Spinal cord stimulation in a mouse chronic neuropathic pain model.
AB  - Objective.  Development of a spinal cord stimulation (SCS) system in a mouse
      model of chronic neuropathic pain. Materials and Methods.  Male C57BL/6 mice (N =
      6) underwent a partial ligation of the sciatic nerve. Development of mechanical
      hyperalgesia was tested using the withdrawal response to tactile stimuli with the
      von Frey test. An SCS system was implanted on day 14. On day 16, the mice were
      stimulated for 30 min (f = 50 Hz; pulse width 0.2 msec and stimulation at 2/3 of
      motor threshold). Repeated measure analysis of variance (anova) and paired
      Student's t-test with Bonferroni correction were used to evaluate the development
      of mechanical hyperalgesia and the therapeutic effect of SCS. Results.  Five out
      of six mice developed marked mechanical hyperalgesia in the nerve-lesioned paw
      that persisted for the duration of the study (16 days). No changes contralateral
      to the injury were observed. In four out of five mice, a successful implantation
      of the electrodes followed by stimulation was achieved. Then, SCS resulted in a
      fast and robust increase of withdrawal threshold back to pre-injury levels. After
      termination of the SCS, the withdrawal threshold of the ipsilateral paw slowly
      decreased. No effect of SCS on the contralateral paw was noted. Conclusion.  The
      development of a mouse SCS system is described that is practical in use, is
      reproducible, and shows a comparative therapeutic effect in treatment of chronic
      neuropathic pain as reported in rat.

PMID- 22150896
TI  - Five-Year Follow-up After Sacral Neuromodulation: Single Center Experience.
AB  - Objective.  We studied long-term clinical efficacy of sacral neuromodulation
      (SNM) therapy in patients with refractory urgency incontinence (UI),
      urgency/frequency (UF) and voiding difficulty (VD), together with urodynamic data
      at baseline and six months postimplant. Materials and Methods.  Twenty-two
      patients were implanted with a neurostimulator after a positive response to a
      percutaneous nerve evaluation test defined as a greater than 50% improvement in
      symptoms. Results.  At five-year follow-up, the number of incontinent episodes
      and pad usage per day decreased significantly in 10 out of 15 UI patients. Two of
      five UF patients were successfully treated with SNM; the number of daily voids
      for all UF patients decreased from 25 to 19 and average voided volume increased
      from 98 to 212 mL. One of the two VD patients was able to void to completion.
      Mean first sensation of filling at the six-month urodynamic investigation for the
      UI and UF patients increased from 78 to 241 mL and 141 to 232 mL, respectively,
      and the maximum bladder capacity increased from 292 to 352 mL and 223 to 318 mL,
      respectively. Five of 22 patients underwent device explant and one patient still
      has an inactive stimulator implanted. Conclusion.  SNM is an effective treatment
      modality that offers sustained clinical benefit in the majority of patients with
      refractory UI, UF, and VD that do not respond to other, more conservative
      therapies.

PMID- 22150897
TI  - Sacral nerve and spinal cord stimulation for intractable neuropathic pain caused
      by spinal cord infarction.
AB  - Central cord pain is very difficult to relieve, even with the many kinds of
      medical and surgical treatments available. Following spinal cord infarctions,
      central cord pain can develop. The problems that may arise could include limb
      pain, pelvic pain, difficulties voiding, and difficulties defecating. We are
      reporting a case of central cord pain caused by a spinal cord infarction of the
      conus medullaris. Limb pain was reduced by spinal cord stimulation. Voiding and
      defecation difficulties and pelvic pain were reduced by sacral nerve stimulation.
      Thus, in a case involving both intractable limb and pelvic pain, a combination
      therapy of these two stimulations might be an effective treatment modality.

PMID- 22150898
TI  - Peripheral nerve stimulation in treatment of intractable postherpetic neuralgia.
AB  - Objective.  This case report presents an application of peripheral nerve
      stimulation to a patient with intractable postherpetic neuralgia that
      conventional treatment failed to ameliorate. Methods.  The patient underwent an
      uneventful peripheral nerve stimulator trial with placement of two temporal eight
      electrode percutaneous leads (Octrode leads, Advanced Neuromodulation Systems,
      Plano, TX, USA) into the right subscapular and right paraspinal area of the upper
      thoracic region. Results.  Upon experiencing excellent pain relief over the next
      two weeks, the patient underwent implantation of permanent leads two weeks later
      and reported sustained pain relief. Conclusion. Peripheral nerve stimulation
      offers an alternative treatment option for intractable pain associated with
      postherpetic neuralgia, especially for elderly patients where treatment options
      are limited due to existing comorbidities. Further studies are warranted.

PMID- 22150899
TI  - The use of implanted programmable infusion pumps in the management of
      nonmalignant, chronic low-back pain.
AB  - Objectives.  To assess the mode-of-use of implanted programmable infusion pumps
      in patients with nonmalignant, chronic low-back pain. Materials and Methods. 
      Charts from 101 consecutive eligible patients were analyzed retrospectively. Data
      were extracted relating to patient demographics, pump mode of infusion and flow
      rate, and medications used. Results.  Morphine was the agent most frequently used
      and most patients received one medication at each visit. At the last visit, 94.1%
      of patients were receiving constant-flow treatment; 90.1% had received such
      treatment for >= six months and 68.3% throughout the entire analysis period. For
      patients attaining constant-flow treatment, mean time from implantation to start
      of such treatment was 2.7 months. Discussion.  The results suggest that many
      patients with nonmalignant low-back pain could be implanted with a constant-flow
      pump when their programmable device needs replacing or, in some cases, at the
      start of intrathecal treatment. This would reduce costs and the requirement for
      surgery.

PMID- 22150900
TI  - Contents to volume 10.

PMID- 22150901
TI  - The p-value - a well-understood and properly used statistical concept?

PMID- 22150902
TI  - Case report: allergic contact cheilitis caused by ceresin wax.

PMID- 22150903
TI  - Positive patch test reaction to Lonicera japonica extract in a patient sensitized
      to formaldehyde.

PMID- 22150904
TI  - Occupational contact urticaria caused by polyvinylchloride gloves.

PMID- 22150905
TI  - Allergic contact dermatitis caused by a skin-lightening agent, 5,5'
      dipropylbiphenyl-2,2'-diol.

PMID- 22150906
TI  - Is pulsed radiofrequency a neuromodulation technique?

PMID- 22150907
TI  - SCS Trial Duration.

PMID- 22150908
TI  - Percutaneous pulsed radiofrequency treatment of the cervical dorsal root ganglion
      in the treatment of chronic cervical pain syndromes: a clinical audit.
AB  - Cervicogenic headache and cervicobrachialgia are frequent diagnoses of chronic
      cervical pain. After failure of conservative treatment, an interventional
      approach may be indicated in the absence of any indication for causal surgical
      treatment. The pulsed radiofrequency (PRF) technique exposes the nerve to a high
      frequency electric field while the temperature of the electrode tip does not
      exceed 42 degrees C. This method is thought to be nondestructive and almost free
      of neurologic side effects and complications. Our extended pilot study was
      performed to confirm the perceived efficacy of PRF for short- and long-term
      relief of chronic cervical pain. We carried out a clinical audit of the first 18
      patients treated with PRF at the cervical dorsal root ganglion. An independent
      evaluator reviewed the medical records. Patients with good clinical results at 8
      weeks were evaluated for long-term effect (> 6 months), based on a 7-point Likert
      scale. Thirteen patients (72%) showed short-term clinical success (>= 50% pain
      relief). Mean follow-up was 19.4 months (SD 8.9 months), maximum 2.5 years. The
      duration of satisfactory pain relief (6 or 7 on the Likert scale) varied between
      2 and over 30 months, with a mean duration of 9.2 months (SD 11.2 months). Kaplan
      Meier analysis illustrated that 50% of patients experienced success 3 months
      after treatment. We could not identify predictive variables for clinical outcome.
      None of the patients reported post-treatment neuritis or other adverse events. To
      our knowledge, this is the first documented series of chronic cervical pain
      syndromes treated with PRF. Satisfactory pain relief of at least 50% was achieved
      in 13 of 18 (72%) patients at 8 weeks. More than one year after treatment, six
      patients (33%) continue to rate treatment outcome as good or very good. No side
      effects were reported. j.

PMID- 22150909
TI  - Acute vs. Prolonged Screening for Spinal Cord Stimulation in Chronic Pain.
AB  - Spinal cord stimulation (SCS) was performed to test the hypothesis that pain
      relief data during acute (15 minute intraoperative) and prolonged (5 day) SCS
      screening have equivalent predictive value for long-term successful SCS control
      of chronic low back pain and/or lower extremity pain. A retrospective series of
      patients with chronic low back and/or lower extremity pain underwent either
      percutaneous or open (ie, laminectomy) SCS implantation during which acute
      intraoperative followed by prolonged screening trials for percentage pain relief
      (%PR) were performed. Data were analyzed for (a) correlation between positive
      predictive value (PPV) of acute and prolonged SCS screening for %PR and (b) PPV
      of acute vs. prolonged screening %PR for long-term SCS %PR. Fifty-four patients
      (male/female = 38/16; mean age +/- SEM = 54.2 +/- 2.0 years) underwent thoracic
      (T) (mean level = T9.1 +/- 0.4) percutaneous (n = 33) and laminectomy (n = 21)
      implantation of SCS for acute (15 minute intraoperative) and prolonged (5.0 +/-
      0.3 days) SCS screening of pain relief. Correlation between successful (> 50%PR)
      pain relief during acute (n = 53/54, PPV = 98%) and prolonged (n = 47/52, PPV =
      90%) screening was significant (Spearman Rank Correlation Coefficient, SRCC =
      0.462, p < 0.01). After permanent SCS implantation, at mean follow-up = 9.4 +/-
      1.5 months, acute and prolonged SCS screening %PR PPV's were each statistically
      significant for predicting long-term SCS relief of chronic pain (n = 31/38, PPV =
      82% and n = 31/36, PPV = 86%, SRCC = 0.462 and 0.433, respectively, p < 0.01). 
      We conclude that successful pain relief during acute SCS screening is highly
      correlated with successful prolonged SCS screening of chronic low back and/or
      lower extremity pain relief. Acute and prolonged SCS screening appear to have
      equivalent predictive value for successful long-term SCS control of chronic low
      back and/or lower extremity pain. These preliminary results suggest potential
      justification for eliminating prolonged and retaining acute (intraoperative) SCS
      screening for selection of permanent SCS implantation candidates.

PMID- 22150910
TI  - Cervical spinal cord stimulation for pain: a report on 41 patients.
AB  - The objectives of this study were to assess the effectiveness of cervical spinal
      cord stimulation in the management of intractable pain syndromes affecting the
      upper limb and face and to assess the reliability of a specific electrode system
      in this mobile environment. Forty-one patients, aged 26-76 years (median 48) with
      neuropathic or ischemic pain underwent the cervical epidural implantation of
      identical dual two-contact paddle (four contacts per system) laminectomy
      electrodes. Follow-up (from 5 months to 11 years, 3 months; median 4 years, 7
      months) was by multiple consultations carried out by the surgeon and/or in a
      nurse-led specialist clinic. Overall, 68% obtained sustained pain relief, rated
      as significant in 51% of the total. Facial pain did not respond. Ischemic
      syndromes responded well. Lead fracture rate was 15% of the original (11% of the
      total including replacements) and only 7% (5%) became dislodged.We conclude that
      the electrode system described provides reliable and sustained cervical cord
      stimulation. The outcomes are comparable with thoracic cord stimulation for
      neuropathic and ischemic syndromes.

PMID- 22150911
TI  - Spinal cord stimulation in the management of pain from brachial plexus avulsion.
AB  - This is a retrospective study of four patients suffering from brachial plexus
      root avulsion of traumatic origin. Spinal cord stimulation was used to treat pain
      in all patients. A seven-contact electrode was percutaneously introduced in the
      epidural cervical space and under fluoroscopic control, advanced to the level
      were stimulation provoked a tingling sensation in the painful region. A
      stimulation trial was performed for 2 weeks and during this period the patients
      showed significant pain relief, so the system was permanently implanted. A
      significant difference of more than three points in the pain between the first
      and the last follow-up (0-9 months) on the Visual Analog Scale was obtained with
      a steady and progressive decrease of the pain scores.

PMID- 22150912
TI  - Prevention of intrathecal drug delivery catheter-related complications.
AB  - In an effort to improve the performance of implantable intrathecal drug delivery
      systems, a group of physicians experienced in the management of such devices
      reviewed surgical practices and principles that were associated with low catheter
      related complication rates. Clinical study and postmarket data identified
      physicians whose patients experienced a relatively low rate of catheter-related
      complications. Six of those physicians (three anesthesiologists and three
      neurosurgeons) reviewed the number and types of intrathecal drug pumps and
      catheters they had implanted, with an emphasis on the specific details of
      successful catheter implantation techniques. The authors pooled their experiences
      to reach a consensus on implant techniques that are associated with a low rate of
      postoperative complications.  The authors found that complications were minimized
      by the use of specific methods for catheter placement that included: a mid-to
      upper lumbar dural entry level, a shallow-angle paramedian oblique insertion
      trajectory, and meticulous catheter anchoring and tunneling techniques. Systemic
      antibiotic prophylaxis, attention to pump pocket location, and surgical wound
      closure techniques also were important in reducing the incidence of postoperative
      device-related complications. Their experience indicates that specific
      implantation techniques using a variety of catheters and accessories can be
      expected to reduce the incidence of complications after implantation of
      intrathecal drug administration systems.

PMID- 22150913
TI  - Mechanisms of electrical stimulation with neural prostheses.
AB  - Individual electric and geometric characteristics of neural substructures can
      have surprising effects on artificially controlled neural signaling. A rule of
      thumb approved for the stimulation of long peripheral axons may not hold when the
      central nervous system is involved. This is demonstrated here with a comparison
      of results from the electrically stimulated cochlea, retina, and spinal cord. A
      generalized form of the activating function together with accurate modeling of
      the neural membrane dynamics are the tools to analyze the excitation mechanisms
      initiated by neural prostheses. Analysis is sometimes possible with a linear
      theory, in other cases, simulation of internal calcium concentration or ion
      channel current fluctuations is needed to see irregularities in spike trains.
      Spike initiation site can easily change within a single target neuron under
      constant stimulation conditions of a cochlear implant. Poor myelinization in the
      soma region of the human cochlear neurons causes firing characteristics different
      from any animal data. Retinal ganglion cells also generate propagating spikes
      within the dendritic tree. Bipolar cells in the retina are expected to respond
      with neurotransmitter release before a spike is generated in the ganglion cell,
      even when they are far away from the electrode. Epidural stimulation of the
      lumbar spinal cord predominantly stimulates large sensory axons in the dorsal
      roots which induce muscle reflex responses. Analysis with the generalized
      activating function, computer simulations of the nonlinear neural membrane
      behavior together with experimental and clinical data analysis enlighten our
      understanding of artificial firing patterns influenced by neural prostheses.

PMID- 22150914
TI  - Stair Ascending and Descending with the Cooperative Neuroprosthesis WALK!
AB  - Neuroprostheses enabling patients to ascend and descend stairs can provide real
      functional gain. A novel finite state control scheme is presented and validated
      experimentally. The motion tasks Ascent and Descent are specified by sequences of
      motion phases for each leg separately. A supervisory controller coordinates
      motion phases and synchronizes left and right leg motion by Control Interpreted
      Petri Nets (CIPN). To switch between motion phases, sensor-based events and
      patient-operated manual switch states are supervised. This increases the
      patients' control of the movements and relieves them of automatizable tasks.
      Experiments with two complete thoracic spinal cord injured (SCI) patients were
      carried out. Transcutaneous stimulation of eight channels is applied by the
      experimental neuroprosthesis WALK! Both patients were able to repeatedly ascend
      and descend platforms of 12 cm and 16.4 cm in height, one patient also was able
      to ascend a staircase (17 cm step height). Feasibility of the approach has been
      successfully demonstrated. Future work will concentrate on improved foot
      clearance during Ascent and closed loop controlled muscle activation in selected
      motion phases of both Ascent and Descent. The approach is also suited for
      implanted lower extremity neuroprostheses.

PMID- 22150915
TI  - Feasibility of using peroneal nerve recordings for deriving stimulation timing in
      a foot drop correction system.
AB  - The objective of this research was to demonstrate the potential of using peroneal
      nerve activity to derive timing control for stimulation in foot drop correction
      and to attempt recording and stimulation through the same electrode. Two subjects
      were implanted with cuff electrodes on the peroneal nerve. An input domain was
      derived from the recorded electroneurogram (ENG) and fed to a detection algorithm
      based on an Adaptive Logic Network (ALN) for predicting stimulation timing. A
      switching circuit was furthermore built for switching between stimulator and
      recorder for combined use of the cuff electrode.  The detection was successful,
      but the accuracy depended on the signal to noise ratio of the recorded ENG. The
      switching circuit successfully allowed for simultaneous recording and stimulation
      through the same cuff electrode. We conclude that the peroneal nerve can
      potentially be used to record sensory information for derivation of a stimulator
      control signal in a foot drop application, while at the same time being
      stimulated to activate foot dorsiflexors.

PMID- 22150916
TI  - Roles of gender, obesity, and lifestyle-related diseases in alcoholic liver
      disease: Obesity does not influence the severity of alcoholic liver disease.
AB  - AIM:   To elucidate gender differences and the influence of obesity and/or
      metabolic syndrome-related fatty liver on alcoholic liver disease (ALD), we
      analyzed characteristic features of ALD. METHODS:   We investigated 266 ALD
      patients (224 males and 42 females) without hepatocellular carcinoma stratified
      by gender and the presence of cirrhosis. Male and female patients matched for age
      and total ethanol intake were also analyzed. A diagnosis of ALD was based on
      alcohol intake (>70 g daily for more than 5 years), clinical features, and
      exclusion of other liver diseases. The prevalence of obesity, lifestyle-related
      diseases, and psychological disorders were assessed. RESULTS:   The prevalence of
      psychological disorders showed a significant gender difference among all ALD
      patients (12% in males versus 43% in females, P < 0.001), as well as in patients
      matched for age and total ethanol intake. There were 156 cirrhotic patients.
      Absence of dyslipidemia, presence of diabetes, and high total ethanol intake were
      selected as independent predictors of cirrhosis in males by multivariate analysis
      after excluding laboratory data of liver function tests. The prevalence of
      obesity was significantly lower in cirrhotic male patients than in non-cirrhotic
      male patients (34% vs. 20%, P = 0.023). Among females, there were no significant
      predictors of cirrhosis on multivariate analysis after eliminating liver function
      tests. The prevalence of obesity and diabetes was similar in non-cirrhotic and
      cirrhotic female patients. The prevalence of psychological disorders was 47% in
      cirrhotic females with ALD. CONCLUSIONS:   Obesity was not common in cirrhotic
      ALD. Psychological disorders seem to be important for female ALD.

PMID- 22150917
TI  - The ratio of glycated albumin to glycated haemoglobin correlates with insulin
      secretory function.
AB  - OBJECTIVE: Although glycated haemoglobin (A1c) levels are similar among patients
      with type 2 diabetes, the glycated albumin (GA)/A1c ratio varies considerably. On
      the basis of the hypothesis that endogenous insulin secretion might be correlated
      with the GA/A1c ratio, we investigated whether insulin secretory function or
      insulin resistance has different effects on the GA/A1c ratio in patients with
      type 2 diabetes using the standardized liquid meal test. DESIGN: A clinical,
      retrospective study. PATIENTS AND MEASUREMENTS: A total of 758 patients with type
      2 diabetes ingested a standardized liquid meal (i.e. 500 kcal, 17.5 g fat, 68.5 g
      carbohydrate and 17.5 g protein). The subjects were divided into two groups:
      those with GA/A1c ratio <2.5 (n = 414) and those with GA/A1c ratio >=2.5 (n =
      344). We compared the A1c and GA levels, and the GA/A1c ratio and evaluated the
      relationships between the glycaemic indices and other parameters. Effects of beta
      cell function [homeostasis model assessment (HOMA-beta), insulinogenic index
      (IGI)] and insulin resistance (HOMA-IR) on the GA/A1c ratio were also examined.
      RESULTS: The GA/A1c ratio was significantly correlated with HOMA-beta, IGI and
      body mass index (BMI) but not with HOMA-IR. Furthermore, after adjusting for age,
      gender, BMI, haemoglobin and albumin levels, the GA/A1c ratio was still inversely
      correlated with both HOMA-beta and IGI. CONCLUSIONS: The GA/A1c ratio is
      significantly correlated with insulin secretory function but not with insulin
      resistance.

PMID- 22150918
TI  - Fracture risk after thiazide-associated hyponatraemia.
AB  - BACKGROUND/AIM: Although thiazide-type diuretics can promote a positive calcium
      balance, thiazide can be associated with hyponatraemia, which is recently linked
      with heightened fracture risk. We examine the chance of developing fracture in
      patients with and without hyponatraemia after taking thiazide diuretics. METHODS:
      In this single-centre retrospective study, we followed up a previously published
      cohort of patients with (n= 223) and without (n= 216) thiazide-induced
      hyponatraemia. RESULTS: A total of 61 osteoporotic fractures was recorded during
      a mean follow-up period of 82 months. Using univariate regression analysis, the
      hazard ratio of thiazide-induced hyponatraemia was 1.78 (95% confidence interval
      (CI), 1.05-3.03; P= 0.033). Cox proportional hazards regression analysis,
      however, showed that age, body mass index and diabetes mellitus were the only
      independent predictors of osteoporotic fractures. No association of a history of
      thiazide-induced hyponatraemia and risk of fracture was evident in the final
      model. CONCLUSION: Since a history of thiazide-induced hyponatraemia is
      associated with osteoporotic fracture in univariate but not multivariate
      analyses, an alternative explanation is that confounding factors of older age and
      low body mass index accounted for the apparently increased risk of osteoporotic
      fracture in patients with thiazide-induced hyponatraemia.

PMID- 22150919
TI  - Brain death in Islamic ethico-legal deliberation: challenges for applied Islamic
      bioethics.
AB  - Since the 1980s, Islamic scholars and medical experts have used the tools of
      Islamic law to formulate ethico-legal opinions on brain death. These assessments
      have varied in their determinations and remain controversial. Some juridical
      councils such as the Organization of Islamic Conferences' Islamic Fiqh Academy
      (OIC-IFA) equate brain death with cardiopulmonary death, while others such as the
      Islamic Organization of Medical Sciences (IOMS) analogize brain death to an
      intermediate state between life and death. Still other councils have repudiated
      the notion entirely. Similarly, the ethico-legal assessments are not uniform in
      their acceptance of brain-stem or whole-brain criteria for death, and
      consequently their conceptualizations of, brain death. Within the medical
      literature, and in the statements of Muslim medical professional societies, brain
      death has been viewed as sanctioned by Islamic law with experts citing the
      aforementioned rulings. Furthermore, health policies around organ transplantation
      and end-of-life care within the Muslim world have been crafted with consideration
      of these representative religious determinations made by transnational, legally
      inclusive, and multidisciplinary councils. The determinations of these councils
      also have bearing upon Muslim clinicians and patients who encounter the
      challenges of brain death at the bedside. For those searching for 'Islamically
      sanctioned' responses that can inform their practice, both the OIC-IFA and IOMS
      verdicts have palpable gaps in their assessments and remain clinically ambiguous.
      In this paper we analyze these verdicts from the perspective of applied Islamic
      bioethics and raise several questions that, if answered by future juridical
      councils, will better meet the needs of clinicians and bioethicists.

PMID- 22150920
TI  - Patients with high body mass index tend to have lower stage of esophageal
      carcinoma at diagnosis.
AB  - High body mass index (H-BMI; >=25 kg/m(2) ) is common in US adults. In a small
      cohort of esophageal cancer (EC) patients treated with surgery, H-BMI and
      diagnosis of early stage EC appeared associated. We evaluated a much larger
      cohort of EC patients. From a prospectively maintained database, we analyzed 925
      EC patients who had surgery with or without adjunctive therapy. Various
      statistical methods were used. Among 925 patients, 69% had H-BMI, and 31% had
      normal body mass index (<25 kg/m(2) ; N-BMI). H-BMI was associated with men
      (P<0.001), Caucasians (P=0.064; trend), lower esophageal localization (P<0.001),
      adenocarcinoma histology (P<0.001), low baseline cT-stage (P=0.003), low baseline
      overall clinical stage (P=0.003), coronary artery disease (P=0.036), and diabetes
      (P<0.001). N-BMI was associated with weight loss (P<0.001), alcohol abuse
      (P=0.056; trend), ever/current smoking (P=0.014), and baseline cN+ (P=0.018). H
      BMI patients with cT1 tumors (n=110) had significantly higher rates of
      gastresophageal reflux disease symptoms (P<0.001), gastresophageal reflux disease
      history (P<0.001), and Barrett's esophagus history (P<0.001) compared with H-BMI
      patients with cT2 tumors (n=114). Median survival of N-BMI patients was 36.66
      months compared with 53.20 months for H-BMI patients (P=0.005). In multivariate
      analysis, older age (P<0.001), squamous histology (P=0.002), smoking (P=0.040),
      weight loss (P=0.002), high baseline stage (P<0.001), high number of ypN+
      (P=0.005), high surgical stage (P<0.001), and American Society of Anesthesia
      scores, three out of four (P<0.001) were independent prognosticators for poor
      overall survival. We were able to perform propensity-based analysis of surgical
      complications between H-BMI and N-BMI patients. A comparison of fully matched 376
      patients (188 with H-BMI and 188 with N-BMI) found no significant differences in
      the rate of complications between the two groups. This larger data set confirms
      that a fraction of H-BMI patients with antecedent history is diagnosed with early
      baseline EC. Upon validation of our data in an independent cohort, refinements in
      surveillance of symptomatic H-BMI patients are warranted and could be
      implemented. Our data also suggest that H-BMI patients do not experience higher
      rate of surgical complications compared with N-BMI patients.

PMID- 22150921
TI  - Associations of serum vitamin D concentrations with obstetric glucose metabolism
      in a subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study
      cohort.
AB  - AIMS: To assess associations between maternal serum vitamin D concentration and
      glucose metabolism in a cohort of pregnant women living in an Australian
      subtropical environment. METHODS: Cross-sectional assessment of 25-hydroxy
      vitamin D concentrations in 399 Hyperglycemia and Adverse Pregnancy Outcome
      ancillary study participants, treated at an obstetric teaching hospital in
      Brisbane, Australia. All patients underwent a blinded 75-g oral glucose tolerance
      test at 24-32 (target 28) weeks' gestation. RESULTS: The mean (+/- standard
      deviation) fasting plasma glucose was 4.5 +/- 0.4 mmol/l. Mean (+/- standard
      deviation) serum 25-hydroxy vitamin D was 132.5 +/- 44.0 nmol/l. A difference of
      one standard deviation in maternal 25-hydroxy vitamin D was inversely related to
      fasting glucose (fasting glucose lower by 0.047 mmol/l, P=0.012) when assessed
      with multiple linear regression after adjusting for confounders. Maternal 25
      hydroxy vitamin D correlated with beta-cell function as estimated by the log
      transformed homeostasis model assessment-beta-cell function equation (r=0.131,
      P=0.009), but not with the homeostasis model assessment of insulin resistance.
      CONCLUSIONS: An association between mid-gestational 25-hydroxy vitamin D and
      fasting glucose was confirmed in a largely normoglycaemic and vitamin D-replete
      pregnant population. The correlation between 25-hydroxy vitamin D and beta-cell
      function suggests that vitamin D may influence glucose metabolism through this
      mechanism. Intervention studies are required to determine causality and the role
      of vitamin D replacement in deficient individuals.

PMID- 22150922
TI  - Introduction. Autophagy dysregulation in neuropathology.

PMID- 22150923
TI  - Autophagy in lysosomal myopathies.
AB  - Lysosomal myopathies are hereditary myopathies characterized morphologically by
      the presence of autophagic vacuoles. In mammals, autophagy plays an important
      role for the turnover of cellular components, particularly in response to
      starvation or glucagons. In normal muscle, autolysosomes or autophagosomes are
      typically inconspicuous. In distinct neuromuscular disorders, however, lysosomes
      become structurally abnormal and functionally impaired, leading to the
      accumulation of autophagic vacuoles in myofibers. In some instances, the
      accumulation of autophagic vacuoles can be a prominent feature, implicating
      autophagy as a contributor to disease pathomechanism and/or progression. At
      present, there are two disorders in the muscle that are associated with a primary
      defect in lysosomal proteins, namely Pompe disease and Danon disease. This review
      will give a brief discussion on these disorders, highlighting the role of
      autophagy in disease progression.

PMID- 22150924
TI  - Autophagy in brain tumors: a new target for therapeutic intervention.
AB  - The role of autophagy, traditionally considered a cellular homeostatic and
      recycling mechanism, has expanded dramatically to include an involvement in
      discrete stages of tumor initiation and development. Gliomas are the most
      aggressive and also the most common brain malignancies. Current treatment
      modalities have only a modest effect on patient outcomes. Resistance to
      apoptosis, a hallmark of most cancers, has driven the search for novel targets in
      cancer therapy. The autophagy lysosomal pathway is one such target that is being
      explored in multiple cancers including gliomas and is a promising avenue for
      further therapeutic development. This review summarizes our current understanding
      of the autophagic process and its potential utility as a target for glioma
      therapy.

PMID- 22150926
TI  - Autophagy dysregulation in amyotrophic lateral sclerosis.
AB  - Autophagy is an intracellular lysosomal degradation process, which plays an
      important role in cell growth and development, and keeping cellular homeostasis
      in all eukaryotes. Autophagy has multiple physiological functions, including
      protein degradation, organelle turnover and response to stress. Emerging
      evidences support the notion that dysregulation of autophagy might be critical
      for pathogenesis of amyotrophic lateral sclerosis (ALS). The autophagy
      dysregulation in motor neurons of ALS may occur in different steps of the
      autophagic process. Recent studies have shown that two ALS associated proteins,
      TDP-43 and superoxide dismutase 1 (SOD1), are involved in the abnormal autophagy
      regulation. Furthermore, it is reported that several genetic mutations in ALS
      disturb the autophagic process in the motor neurons. This review will provide new
      evidence of autophagy dysregulation as a critical pathogenic process leading to
      ALS, and will discuss the prospect of future therapeutic targets using autophagic
      regulation to treat this disease.

PMID- 22150927
TI  - Man with posterior fossa tumors 15 years apart.
AB  - A 48-year-old man with a history of hypertension, peripheral vascular disease and
      a 50-pack-year history of smoking presented with new onset vertigo, tinnitus,
      diplopia and ataxia in January 1978. CT scan showed a radiolucent defect in the
      left cerebellar hemisphere with a possible mural nodule. In ensuing months, he
      experienced worsening symptoms with a corresponding increase in lesion size on re
      imaging. Months later, a left posterior fossa craniotomy was performed and
      revealed a single cystic lesion containing copious amounts of straw-colored fluid
      and a single mural nodule in the inferior portion of the cyst. Following
      resection, he was followed clinically until 1985 at which time follow-up was
      discontinued. He did well until January 1993 when he presented with progressively
      worsening episodic headaches and retro-orbital pressure. Subsequent MRIs of the
      brain and spine (February 1993, March 1993) showed multiple lesions along the
      neuraxis involving the superficial brain parenchyma, leptomeninges, and dura.
      Despite therapy, his condition progressively declined until he succumbed. A brain
      only autopsy revealed numerous small tumor nodules involving the base of the
      brain over both frontal and temporal lobes, midbrain, pons, right optic nerve,
      pituitary fossa, and the base of the skull. Pathologic evaluation revealed
      metastatic hemangioblastoma. Metastatic hemangioblastoma is a rare entity, with
      only a few reported cases in the literature to date.

PMID- 22150928
TI  - A 2-year-old boy with hemolytic uremic syndrome and pneumocephalus.
AB  - Clostridium septicum infection following hemolytic uremic syndrome is rare and
      carries a poor prognosis, especially when the brain is involved. We report a case
      of a previously healthy 2-year-old boy who presented with two days of anuria and
      bloody diarrhea. He was admitted to the local children's hospital with a
      diagnosis of hemolytic uremic syndrome, presumably secondary to E. coli O157. He
      soon required intubation and was noted to have fixed and dilated pupils. Head CT
      revealed left frontal subcortical white matter vasogenic edema and scattered
      pockets of pneumocephalus. The patient expired 14 hours after admission.
      Antemortem blood cultures grew C. septicum. Gross pathologic examination of the
      brain revealed a large intraparenchymal cerebral hemorrhage in the left frontal
      and parietal lobes. There was extensive cystic changes as well. Microscopic
      examination revealed vacuolization and diffuse colonization with rod-shaped
      bacteria, but without the expected tissue response. There have been only six
      previously reported cases of C. septicum infection following hemolytic uremic
      syndrome, four of which had brain involvement. Mortality rate is high, with the
      only known survivor among those with brain involvement having a brain abscess
      rather than diffuse pneumocephalus.

PMID- 22150925
TI  - Autophagy in dementias.
AB  - Dementias are a varied group of disorders typically associated with memory loss,
      impaired judgment and/or language and by symptoms affecting other cognitive and
      social abilities to a degree that interferes with daily functioning. Alzheimer's
      disease (AD) is the most common cause of a progressive dementia, followed by
      dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), (VaD) and HIV
      associated neurocognitive disorders (HAND). The pathogenesis of this group of
      disorders has been linked to the abnormal accumulation of proteins in the brains
      of affected individuals, which in turn has been related to deficits in protein
      clearance. Autophagy is a key cellular protein clearance pathway with proteolytic
      cleavage and degradation via the ubiquitin-proteasome pathway representing
      another important clearance mechanism. Alterations in the levels of autophagy and
      the proteins associated with the autophagocytic pathway have been reported in
      various types of dementias. This review will examine recent literature across
      these disorders and highlight a common theme of altered autophagy across the
      spectrum of the dementias.

PMID- 22150931
TI  - A specific sign for differential diagnosis of atypical atrioventricular nodal
      reentrant tachycardia from atrial tachycardia.
AB  - Narrow QRS tachycardia with atrial activation occurring before ventricular
      activation was induced in a 34-year-old woman with dilated cardiomyopathy. During
      tachycardia late ventricular extrastimulus delivered when His bundle was
      refractory failed to reset the tachycardia while early ventricular extrastimulus
      caused paradoxical delay of the subsequent atrial response and terminated the
      tachycardia with a QRS not being followed by an atrial response. This is a rare
      but specific sign for excluding atrial reentry as the mechanism of tachycardia
      when P wave or atrial activation is registered before QRS response.

PMID- 22150932
TI  - The future is bright for The Plant Journal, now in its 20th year.

PMID- 22150933
TI  - Influence of counting chamber type on CASA outcomes of equine semen analysis.
AB  - REASONS FOR PERFORMING STUDY: Sperm motility is considered to be one of the key
      features of semen analysis. Assessment of motility is frequently performed using
      computer-assisted sperm analysis (CASA). Nevertheless, no uniform standards are
      present to analyse a semen sample using CASA. OBJECTIVES: We hypothesised that
      the type of counting chamber used might influence the results of analysis and
      aimed to study the effect of chamber type on estimated concentration and motility
      of an equine semen sample assessed using CASA. METHODS: Commonly used disposable
      Leja chambers of different depths were compared with disposable and reusable ISAS
      chambers, a Makler chamber and a World Health Organization (WHO) motility slide.
      Motility parameters and concentrations obtained with CASA using these different
      chambers were analysed. The NucleoCounter was used as gold standard for
      determining concentration. RESULTS: Concentration and motility parameters were
      significantly influenced by the chamber type used. Using the NucleoCounter as the
      gold standard for determining concentration, the correlation coefficients were
      low for all of the various chambers evaluated, with the exception of the 12 um
      deep Leja chamber. Filling a chamber by capillary forces resulted in a lower
      observed concentration and reduced motility parameters. All chambers evaluated in
      this study resulted in significant lower progressive motility than the WHO
      prepared slide, with the exception of the Makler chamber, which resulted in a
      slight, but statistically significant, increase in progressive motility
      estimates. CONCLUSIONS AND POTENTIAL RELEVANCE: Computer-assisted sperm analysis
      can only provide a rough estimate of sperm concentration and overestimation is
      likely when drop-filled slides with a coverslip are used. Motility estimates
      using CASA are highly influenced by the counting chamber; therefore, a complete
      description of the chamber type used should be provided in semen reports and in
      scientific articles.

PMID- 22150934
TI  - Biocompatibility and bone formation with porous modified PMMA in normal and
      irradiated mandibular tissue.
AB  - A cemented mandibular endoprosthesis is a potentially viable option for
      mandibular reconstruction after ablative surgery. The commonly used PMMA cement
      has the inherent weakness of a lack of bioactivity. Improvement by the addition
      of porosities and bioactive compounds like calcium phosphates may resolve this
      issue. OBJECTIVE: The objective of this study was to assess the bone and tissue
      response to two modified PMMA cements with post-operative radiation as an
      additional influencing factor. MATERIALS & METHODS: An in vivo animal study was
      performed using a mandibular rabbit model. A porous PMMA cement (A) and a porous
      cement incorporated with Beta-tricalcium phosphate particles (b-TCP) (B) were
      placed in bilateral mandibular defects with exposed roots and mandibular nerve of
      20 animals. Half of the animals underwent additional post-operative radiation.
      RESULTS: The animals were healthy with only a minor complication in one rabbit.
      Temperature analysis showed no significant risk of thermal necrosis with the
      maximal in vivo cement temperature at 37.8 degrees C. Histology demonstrated: (1)
      good bone ingrowth around the defect as well as within the pores of the cement
      and defect bridging was achieved in 70% of the specimens after 12-15 weeks of
      implantation, (2) no pulpal injury with minor secondary cementum response, (3) an
      intact mandibular nerve with no inflammation, (4) extensive degradation and
      resorption of the b-TCP particles by 12-15 weeks, and (5) presence of an
      intervening thin fibrous tissue at the bone-to-cement interface.
      Histomorphometrical analysis revealed that there was no difference between the
      different cements and the presence or absence of post-operative radiation. The 12
      15 weeks specimens showed significantly more bone ingrowth and bone maturity than
      the 4-7 weeks specimens. CONCLUSION: Both modified PMMA cements have good
      biocompatibility, bioactivity and support bone ingrowth and additional post
      operative radiation did not show any negative effects.

PMID- 22150936
TI  - Rectal washout and local recurrence in rectal resection for cancer: a meta
      analysis.
AB  - AIM: The effectiveness of rectal washout was compared with no washout for the
      prevention of local recurrence after anterior rectal resection for rectal cancer.
      METHOD: The following electronic databases were searched: PubMed, OVID Medline,
      Cochrane Database of Systematic Reviews, EBM Reviews, CINAHL and EMBASE. RESULTS:
      Five nonrandomized studies including a total of 5012 patients were identified.
      Meta-analysis suggested that rectal washout significantly reduced the local
      recurrence rate (P < 0.0001; OR 0.57; 95% CI 0.43-0.74). It was also
      significantly lower after washout in patients having radical resection only (P =
      0.0004; OR 0.54; 95% CI 0.39-0.76), patients treated by a curative resection (P <
      0.0001; OR 0.55; 95% CI 0.42-0.72) and those undergoing preoperative radiotherapy
      (P = 0.04; OR 0.62; 95% CI 0.39-0.98). CONCLUSION: Taking into account the
      limitations of the design of the included studies the meta-analysis showed that
      rectal washout is associated with reduced local recurrence and therefore should
      be routine during anterior resection for rectal cancer.

PMID- 22150935
TI  - Gender and cervical artery dissection.
AB  - BACKGROUND AND PURPOSE: To analyze previously established gender differences in
      cervical artery dissection (CeAD). METHODS: This case-control study is based on
      the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) population
      comprising 983 consecutive CeAD patients (mean age: 44.1 +/- 9.9 years) and 658
      control patients with a non-CeAD ischemic stroke (IS) (44.5 +/- 10.5 years).
      RESULTS: Cervical artery dissection was more common in men (56.7% vs. 43.3%, P <
      0.001) and men were older (46.4 vs. 41.0 years, P < 0.001). We assessed putative
      risk factors for CeAD including vascular risk factors, recent cervical trauma,
      pregnancies, and infections. All gender differences in the putative risk factors
      and outcome were similar in the CeAD and the non-CeAD IS groups. CONCLUSION: Our
      analysis of the largest collection of CeAD patients to date confirms male
      predominance and differences in age at dissection between men and women. Gender
      differences in putative risk factors may explain the higher frequency of CeAD in
      men and their older age, but the putative risk factors are probably not specific
      for CeAD.

PMID- 22150937
TI  - Concepts and methods in neuromodulation and functional electrical stimulation: an
      introduction.
AB  - This article introduces two clinical fields in which stimulation is applied to
      the nervous system: neuromodulation and functional electrical stimulation. The
      concepts underlying these fields and their main clinical applications, as well as
      the methods and techniques used in each field, are described. Concepts and
      techniques common in one field that might be beneficial to the other are
      discussed.

PMID- 22150938
TI  - Epidural spinal cord stimulation: anatomical and electrical properties of the
      intraspinal structures relevant to spinal cord stimulation and clinical
      correlations.
AB  - Epidural spinal cord stimulation (SCS) has gained a secure place in the
      armamentarium of the surgeon treating chronic pain conditions (1, 2). The
      complexity of the intraspinal structures and their different susceptibility to
      electrical signals, however, has made it difficult to characterize the effects of
      the stimulation, Some important recent work has helped shed light on the
      electrical properties of the intraspinal structures and on the electrical field
      potentials generated with epidural spinal cord stimulation. This work, initially
      pioneered by Sin and Coburn, has successfully been expanded and perfected by
      Holsheimer and Strujik at the University of Twente, The Netherlands (3-8). The
      Dutch scientists developed a computerized volume conductor model of the spinal
      cord to represent in extreme detail the electrical properties of all the
      intraspinal structures, including the dorsal column and dorsal root fibers. The
      model can simulate the effects of epidural stimulation with different electrode
      geometries and configurations (8). The data generated from the model were then
      validated by comparing them to a large number of data collected by the author in
      implanted subjects (9-12). The author also conducted a detailed analysis of the
      clinical properties of the activation of the intraspinal structures at various
      electrode positions in the spine (13, 14).

PMID- 22150939
TI  - Spinal Cord Stimulation and the Induction of c-fos and Heat Shock Protein 72 in
      the Central Nervous System of Rats.
AB  - For more than a decade, spinal cord stimulation (SCS) has been used as an
      adjuvant treatment for patients who are unresponsive to conventional therapies
      for angina pectoris. Many studies showed that SCS has both electro-analgesic and
      anti-ischemic effects. Nonetheless, the biological substrates by which SCS acts
      have not yet been unraveled, although recently areas in the brain have been
      described that show changes in blood flow, following SCS, and during provocation
      of angina. In search of a putative mechanism of action of SCS, we hypothesized
      that SCS affects processing of nociceptive information within the central nervous
      system (CNS). Moreover, it may alter the limbic system activity that maintains
      the balance between sympathetic and parasympathetic activity in the heart. Hence,
      we have developed a rat model to investigate its suitability for studying the
      induction of neural activity during SCS. To characterize neural activity, we used
      the expression of both the immediate early gene c-fos and the heat shock protein
      72 (HSP72). c-Fos was used to identify structures in the CNS affected by SCS, and
      HSP72 was applied in order to ascertain whether SCS might operate as a stressor.
      In 20 halothane-anesthetized male Wistar rats, two electrodes were placed
      epidurally, one at the C7 level and the other at the T2 level. Two days after
      surgery, the rats were either stimulated "treated" animals, n = 10) or used as
      controls ("unstimulated" = "sham," n = 10) in random order. Furthermore, we
      studied the effect of SCS on behavior in five treated and five control rats.
      Three hours after stimulation, the rats were euthanized and the brain and spinal
      cord were removed. The treated group showed regional increased c-fos expression
      in regions of the limbic system (periaqueductal gray, paraventricular
      hypothalamic nucleus, paraventricular thalamic nucleus, central amygdala,
      agranular and dysgranular insular cortex, (peri)ambiguus, nucleus tractus
      solitarius, and spinal cord) that are involved in the processing of pain and
      cardiovascular regulation, among other things. Moreover, in both treated rats and
      controls, HSP72-expression was found in the endothelium of the enthorhinal
      cortex, the amygdala, and the ventral hypothalamus, but not in the neurons.
      Finally, treated animals were significantly more alert and active than controls.
      In conclusion, the rat model we developed appears to be suitable for studying
      potential mechanisms through which SCS may act. In addition, SCS affects c-fos
      expression in specific parts of the brain known to be involved in regulation of
      pain and emotions. HSP72-expression is limited to the endothelium of certain
      parts of the CNS and thereby excludes physical stress effects as a potential
      mechanism of SCS.

PMID- 22150940
TI  - Continuous intrathecal infusion of opioid and bupivacaine in the treatment of
      refractory pain due to postherpetic neuralgia: a case report.
AB  - This report details the course of a 77-year-old patient suffering mild pain from
      operated tongue cancer and excruciating, intractable pain from thoracic (T6-T8)
      post-herpetic neuralgia (PHN), The mouth pain was treated with nonopioid
      analgesics, as the patient had personal objections to opioid treatment. All the
      components of the pain from his PHN (continuous burning pain, intermittent
      lancinating stabbing pain, and tactile allodynia) were successfully treated with
      an Intrathecal Infusion of buprenorphine (0.03 mg/ml) and bupivacaine (4.75
      mg/ml) administered via an externalized intrathecal catheter with the tip located
      at T9-T10 intervertebral disc. The treatment started three months after the
      appearance of the herpetic eruption and lasted 294 days until the patient died of
      malnutrition and the progression of his tongue cancer. During treatment, he
      experienced satisfactory pain relief from his PHN; the mean visual analogue
      scores (VASmean), recorded on a scale from 0 to 10, ranged from 1 to 2, compared
      to 9 to 10 before starting the intrathecal treatment. Analgesia was established
      with 0.2-0.315 mg/day of intrathecal buprenorphine and 90-100 mg/day of
      intrathecal bupivacaine. His undisturbed nocturnal sleep increased from 4 to 5-6
      hours. The side-effects from the bupivacaine (urine retention requiring insertion
      of an indwelling urinary catheter, paresthesias, and mild pareses) were recorded.
      The patient could ambulate without support while on 90-100 mg/day of intrathecal
      bupivacaine. During a series of high-pressure oxygen treatments in a pressure
      chamber to treat an infection at the site of his tumor, the intrathecal infusion
      was interrupted. Thus, repeated observation of the intervals of severe pain and
      of analgesia were possible.

PMID- 22150941
TI  - Reevaluation of the Role of the Sympathetic Nervous System in Cutaneous
      Vasodilation during Dorsal Spinal Cord Stimulation: Are Multiple Mechanisms
      Active?
AB  - Objective. In addition to treatment of refractory chronic pain in patients with
      peripheral vascular disease, dorsal spinal cord stimulation (DCS) increases
      cutaneous blood flow to the extremities and may have a limb-saving effect. The
      purpose of this study was to examine the role of the sympathetic nervous system
      in the cutaneous vasodilation due to DCS. Methods. Male Sprague-Dawley rats were
      anesthetized with pentobarbital (60 mg/kg, i.p.). A unipolar ball electrode was
      placed on the left side of the exposed spinal cord at approximately the L1-L2
      level. Blood flow was concurrently recorded from both hindpaw foot pads with
      laser Doppler flowmeters. Blood flow responses were assessed during 1 min of DCS
      (0.6 mA at 50 Hz, 0.2 msec pulse duration) at 10 min intervals. To determine the
      contribution of the sympathetic nervous system in the blood flow response to DCS,
      the role of ganglionic transmission, alpha-adrenergic receptors, beta-adrenergic
      receptors, and adrenal catecholamine secretion were investigated using adrenergic
      receptor antagonists. Results. Hexamethonium (10 mg/kg, i.v.), an autonomic
      ganglionic receptor antagonist, did not attenuate the cutaneous vasodilation
      during DCS. Phentolamine (3 mg/kg, i.v.), a nonselective alpha-adrenergic
      receptor antagonist, also did not attenuate the DCS-induced increase in
      peripheral cutaneous blood flow. On the other hand, prazosin (0.1 mg/kg, i.v.), a
      selective alpha-1-adrenergic receptor antagonist, attenuated the DCS response but
      this may, at least, be partly due to a vehicle effect. Propranolol (5 mg/kg,
      i.v.), a nonselective beta-adrenergic receptor antagonist, attenuated the DCS
      response while adrenal demedullation did not. Conclusion. Overall, our results
      show that DCS-induced vasodilation can occur through mechanisms that are
      independent of sympathetic outflow.

PMID- 22150942
TI  - The N-terminal hydrophobic segment of Streptomyces coelicolor FtsY forms a
      transmembrane structure to stabilize its membrane localization.
AB  - FtsY is the receptor of the signal recognition particle that mediates the
      targeting of integral membrane proteins in bacteria. It was shown that in
      Escherichia coli, the N-terminal region of FtsY contributes to its interaction
      with the membrane, but it is not inserted into the membrane. However, this study
      presents evidence that in Streptomyces coelicolor, FtsY has a hydrophobic region
      at its N-terminus, which forms a membrane insertion structure and contributes
      significantly to the binding between FtsY and membrane. Through membrane protein
      extraction followed by immunoblotting, we demonstrated that deletion of the N
      terminal residues 11-39 from the S. coelicolor FtsY (ScFtsY) drastically reduced
      its membrane-binding capability and that the N-terminus of ScFtsY alone was
      capable of targeting the soluble EGFP protein onto the membrane with high
      efficiency. Furthermore, in a labeling experiment with the membrane-impermeable
      probe Mal-PEG, the ScFtsY N-terminal region was protected by the membrane and was
      not labeled. This observation indicates that this region was inserted into the
      membrane.

PMID- 22150943
TI  - Breastfeeding is the cornerstone of childhood nutrition.

PMID- 22150944
TI  - Pressure ulcers in older hospitalised patients and its impact on length of stay:
      a retrospective observational study.
AB  - OBJECTIVE: To examine the effect of pressure ulcers in older patients on the
      length of stay in hospital. BACKGROUND: Previous research on this topic did not
      focus solely on older people. A growing number of older people require hospital
      admission. DESIGN: A retrospective observational study. METHODS: Data of 3198
      patients age 75 years and older were included. The setting was a 1350-bed German
      University Hospital. Data were drawn from quality indicator data recorded by
      nurses. The independent effect of pressure ulcers was analysed using a
      multivariate Poisson-Regression model. RESULTS: Of the participants, 7.1% had an
      ulcer during their hospitalisation. 87.3% were classified as categories I and II.
      Mean age was 81.6 years for all patients and 83.2 years for pressure ulcer
      patients. Pressure ulcer patients had a longer overall hospital stay (19.0 vs.
      9.9 days) and a higher excess length of stay (2.6 vs. 0.3 days). Pressure ulcers
      had a statistically significant effect (p = 0.0011) on the increase in length of
      stay. The impact of hospital acquired pressure ulcers on length of stay was more
      pronounced compared to those ulcers being present on admission. The pressure
      ulcer category was not significant. CONCLUSIONS: Pressure ulcers during
      hospitalisation are an independent and significant predictor of a prolonged
      inpatient stay for elderly patients. This study indicates that besides
      complications and co-morbidities social factors, as well as the hospital's
      internal processes of patient care, also can play a significant role. RELEVANCE
      TO CLINICAL PRACTICE: To evaluate the distinct role of hospital acquired pressure
      ulcers further research is needed. The elderly patients in this study were a
      heterogeneous group. The implementation of clinical and nursing processes for
      both the 'fit' and the 'sick' geriatric patients is an important challenge.

PMID- 22150945
TI  - Chemical stability of an admixture combining ziconotide and bupivacaine during
      simulated intrathecal administration.
AB  - Objective.  To determine the stability of an admixture combining ziconotide with
      bupivacaine hydrochloride during simulated intrathecal infusion under laboratory
      conditions at 37 degrees . Materials and Methods.  An admixture containing
      ziconotide (25 ug/mL) and bupivacaine hydrochloride (5 mg/mL) was stored in
      SynchroMed(r) II pumps at 37 degrees  and in control vials at either 37 degrees 
      or 5 degrees . Using high-performance liquid chromatography, drug concentrations
      were determined from samples obtained at varying intervals during the 30-day
      study. Results.  After 30 days, pump ziconotide and bupivacaine hydrochloride
      concentrations measured an average of 86.9% and 99.4% of their initial
      concentrations, respectively. Control vials displayed similar degradation rates
      for both drugs. Statistical evaluation of the ziconotide 95% confidence interval
      indicated that the ziconotide concentration would meet or exceed 90% and 80% of
      initial concentration for 22 days and 45 days, respectively. Conclusions.  An
      admixture containing 25 ug/mL ziconotide and 5 mg/mL bupivacaine hydrochloride
      was 90% stable for 22 days and 80% stable for 45 days (extrapolated) in
      SynchroMed(r) II infusion pumps.

PMID- 22150946
TI  - Chemical stability of ziconotide-clonidine hydrochloride admixtures with and
      without morphine sulfate during simulated intrathecal administration.
AB  - Objective.  To determine the stability of ziconotide-clonidine hydrochloride
      admixtures with and without morphine sulfate during simulated intrathecal
      infusion under laboratory conditions at 37 degrees . Materials and Methods. 
      Admixtures of ziconotide (25 ug/mL) and clonidine hydrochloride (2 mg/mL) with
      and without morphine sulfate (35 mg/mL) were stored in Medtronic SynchroMed(r) II
      pumps at 37 degrees . Pumps were sampled immediately after filling and at four
      additional time points over the course of 28 (ziconotide-clonidine hydrochloride
      admixture) or 20 (ziconotide-clonidine hydrochloride-morphine sulfate admixture)
      days. Drug concentrations were determined using high-performance liquid
      chromatography. Results.  Ziconotide concentration exceeded 97% of initial at all
      time points when combined with clonidine alone; statistical evaluation indicated
      that both ziconotide and clonidine concentrations would remain above 90% of
      initial for more than 60 days. When compounded with both clonidine and morphine,
      ziconotide and clonidine concentrations declined; statistical evaluation
      indicated that the ziconotide concentration was 70% of initial after 20 days, and
      that clonidine would remain 90% stable for 42 days. Morphine was stable in the
      presence of ziconotide and clonidine. Conclusions.  A ziconotide-clonidine
      admixture was 90% stable for 60 days (extrapolated), and a ziconotide-clonidine
      morphine admixture was 70% stable for 20 days.

PMID- 22150947
TI  - Chemical stability of admixtures combining ziconotide with baclofen during
      simulated intrathecal administration.
AB  - Objective.  To determine the stability of admixtures combining ziconotide with
      commercially formulated or powdered baclofen during simulated intrathecal
      infusion under laboratory conditions at 37 degrees . Materials and Methods. 
      Admixtures of ziconotide (25 ug/mL) with commercially formulated (1.5 mg/mL) or
      powdered (2.0 mg/mL) baclofen were stored in implantable intrathecal pumps at 37
      degrees . Drug concentrations were determined with high-performance liquid
      chromatography, and the length of time that the concentrations of both drugs
      remained >=90% and >=80% of initial (ie, the 90% and 80% stability, respectively)
      was estimated based on lower 95% confidence bounds obtained via linear
      regression. Results.  Baclofen was stable in both admixtures. In the commercially
      formulated baclofen admixture, the mean ziconotide concentration declined to
      82.2% of initial in 30 days; the estimates for 90% and 80% stability were 12 and
      29 days, respectively. In the powdered baclofen admixture, the mean ziconotide
      concentration declined to 87.4% of initial in 30 days; the estimates for 90% and
      80% stability were 20 and 41 days, respectively. Conclusion.  Ziconotide-baclofen
      admixtures were more stable when prepared using powdered baclofen rather than a
      commercial baclofen formulation.

PMID- 22150948
TI  - Genetic mapping of quantitative phenotypic traits in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae has become a favorite production organism in industrial
      biotechnology presenting new challenges to yeast engineers in terms of
      introducing advantageous traits such as stress tolerances. Exploring subspecies
      diversity of S. cerevisiae has identified strains that bear industrially relevant
      phenotypic traits. Provided that the genetic basis of such phenotypic traits can
      be identified inverse engineering allows the targeted modification of production
      strains. Most phenotypic traits of interest in S. cerevisiae strains are
      quantitative, meaning that they are controlled by multiple genetic loci referred
      to as quantitative trait loci (QTL). A straightforward approach to identify the
      genetic basis of quantitative traits is QTL mapping which aims at the allocation
      of the genetic determinants to regions in the genome. The application of high
      density oligonucleotide arrays and whole-genome re-sequencing to detect genetic
      variations between strains has facilitated the detection of large numbers of
      molecular markers thus allowing high-resolution QTL mapping over the entire
      genome. This review focuses on the basic principle and state of the art of QTL
      mapping in S. cerevisiae. Furthermore we discuss several approaches developed
      during the last decade that allow down-scaling of the regions identified by QTL
      mapping to the gene level. We also emphasize the particular challenges of QTL
      mapping in nonlaboratory strains of S. cerevisiae.

PMID- 22150949
TI  - Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation?
AB  - The aim of this study was to analyze the relationship between pre-transplant
      adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months
      post-transplantation, and preclinical atherosclerosis in non-diabetic patients
      prior to kidney transplantation (KT). METHODS: We carried out a multicenter study
      in 157 non-diabetic KT patients (66.5% men; age: 50+/-13 yr). Pre-ADP levels were
      analyzed using radioimmunoassay. Carotid ultrasound was performed to determine
      carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried
      out to classify patients according ADA criteria. RESULTS: Of the patients, 52.8%
      had AGH. Median pre-ADP was 19.5 (14-27) MUg/mL. An inverse correlation was found
      between ADP and HOMA index (r=-0.432; p<0.001). Median c-IMT was 0.6 (0.48-0.71)
      mm. Significant inverse correlation existed between ADP and c-IMT on both sides
      (p<0.05). Patients with c-IMT >0.6 mm had more AGH (p=0.012) and lower ADP levels
      (p=0.02). We performed a logistic regression analysis using preclinical
      atherosclerosis (c-IMT >=0.6 mm) as dependent variable and sex, age, BMI, ADP,
      AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and
      AGH were independent risk factors for elevated c-IMT. CONCLUSIONS: Patients with
      AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse
      relationship with AGH and is an independent marker of preclinical
      atherosclerosis.

PMID- 22150950
TI  - Risk of hepatitis B reactivation in patients treated with tumor necrosis factor
      alpha inhibitors.
AB  - The use of tumor necrosis factor-alpha (TNF-alpha) inhibitors has been increasing
      especially in patients with rheumatoid arthritis (RA). As TNF-alpha inhibitors
      are strongly immunosuppressive, the occurrence of hepatitis B virus (HBV)
      reactivation has recently been observed. Reports suggest a higher risk of
      complicating HBV reactivation in carriers who are treated with TNF-alpha
      inhibitors. Therefore, HBV carriers are recommended to undergo prophylactic
      administration of nucleos(t)ide analogs (NAs). Our literary analysis uncovered
      several characteristics of de novo hepatitis B due to TNF-alpha inhibitors.
      First, the time between the start of TNF-alpha inhibitors and the occurrence of
      de novo hepatitis was longer than one year. Second, patients were usually treated
      with additional non-biologic agents, which also had immunosuppressive effects.
      Third, the disease could be fatal. Fourth, several types of TNF-alpha inhibitors
      exhibited a risk of developing de novo hepatitis. Although the incidence of de
      novo hepatitis B varied among reports (0-5%/year), it is suggested that patients
      with prior HBV infection are at risk of developing de novo hepatitis due to TNF
      alpha inhibitors. Many reports maintain that regular measurement of HBV DNA is
      effective in preventing de novo hepatitis. Prophylactic administration of NAs is
      also considered useful to avoid de novo hepatitis, although the issue of cost
      effectiveness needs to be addressed. Lastly, whereas maintenance of circulating
      anti-HBs titer using HB vaccines may be effective in responders to prevent de
      novo hepatitis, further studies are required to clarify the utility of HB
      vaccination.

PMID- 22150951
TI  - The conjugation protein TcpC from Clostridium perfringens is structurally related
      to the type IV secretion system protein VirB8 from Gram-negative bacteria.
AB  - Bacterial conjugation is important for the acquisition of virulence and
      antibiotic resistance genes. We investigated the mechanism of conjugation in Gram
      positive pathogens using a model plasmid pCW3 from Clostridium perfringens. pCW3
      encodes tetracycline resistance and contains the tcp locus, which is essential
      for conjugation. We showed that the unique TcpC protein (359 amino acids, 41 kDa)
      was required for efficient conjugative transfer, localized to the cell membrane
      independently of other conjugation proteins, and that membrane localization was
      important for its function, oligomerization and interaction with the conjugation
      proteins TcpA, TcpH and TcpG. The crystal structure of the C-terminal component
      of TcpC (TcpC(99-359)) was determined to 1.8-A resolution. TcpC(99-359) contained
      two NTF2-like domains separated by a short linker. Unexpectedly, comparative
      structural analysis showed that each of these domains was structurally homologous
      to the periplasmic region of VirB8, a component of the type IV secretion system
      from Agrobacterium tumefaciens. Bacterial two-hybrid studies revealed that the C
      terminal domain was critical for interactions with other conjugation proteins.
      The N-terminal region of TcpC was required for efficient conjugation,
      oligomerization and protein-protein interactions. We conclude that by forming
      oligomeric complexes, TcpC contributes to the stability and integrity of the
      conjugation apparatus, facilitating efficient pCW3 transfer.

PMID- 22150952
TI  - The power of one and saving private Braillon.

PMID- 22150953
TI  - Autoimmune hepatitis - learning about your patients from their autoantibody
      profiles.

PMID- 22150954
TI  - Left main disease associated with an anomalous left anterior descending artery.
AB  - BACKGROUND: Coronary artery anomalies are very rare. Recognizing these anomalies
      are clinically relevant as they can mimic symptoms of coronary artery disease,
      and sporadic cases of sudden death have been described in these patients. METHOD:
      This report describes a 55-year-old patient with left main disease and an
      anomalous left anterior descending artery arising from anterior coronary sinus
      who presented with palpitations. RESULT: Patient underwent coronary artery bypass
      grafting with left internal mammary artery to the ramus intermedius with
      cardiopulmonary bypass using antegrade blood cardioplegia. The anomalous left
      anterior descending artery was crossing the right ventricular outflow tract and
      running on the interventricular groove. CONCLUSION: The diagnosis and management
      of coronary artery anomalies is the subject of this review.

PMID- 22150955
TI  - Epigenetic and genetic disturbance of the imprinted 11p15 region in Beckwith
      Wiedemann and Silver-Russell syndromes.
AB  - Genomic imprinting is a particularly attractive example of epigenetic regulation
      leading to the parental-origin-specific expression of genes. In several ways, the
      11p15 imprinted region is an exemplary model for regulation of genomic
      imprinting. The two imprinted domains are controlled by imprinting control
      regions (ICRs) which carry opposite germ line imprints and they are regulated by
      two major mechanisms of imprinting control. Dysregulation of 11p15 genomic
      imprinting results in two fetal growth disorders [Silver-Russell (SRS) and
      Beckwith-Wiedemann (BWS) syndromes], with opposite growth phenotypes. BWS and SRS
      result from abnormal imprinting involving either, both domains or only one of
      them, with ICR1 and ICR2 more often involved in SRS and BWS respectively. DNA
      methylation defects affecting ICR1 or ICR2 account for approximately 60% of SRS
      and BWS patients. Recent studies have identified new cis-acting regulatory
      elements, as well as new trans-acting factors involved in the regulation of 11p15
      imprinting, therefore establishing new mechanisms of BWS and SRS. Those studies
      also showed that, apart of CTCF, other transcription factors, including factors
      of the pluripotency network, play a crucial role in the regulation of 11p15
      genomic imprinting. Those new findings have direct consequences in molecular
      testing, risk assessment and genetic counseling of BWS and SRS patients.

PMID- 22150956
TI  - A criminological perspective: why prohibition of organ trade is not effective and
      how the Declaration of Istanbul can move forward.
AB  - The Declaration of Istanbul is the first document that has been established by
      the international transplant community that defines and prohibits transplant
      commercialism and organ trafficking. Its Custodian Group has successfully led
      various countries to implement legislation against trafficking and commercialism.
      The question arises, however, whether efforts to prohibit organ trade are
      realistic and effective. The Declaration differentiates trafficking from
      commercialism, yet it does not mention how both acts should be approached by
      policy. Policies that address transplant commercialism work differently from
      policies that tackle organ trafficking. There is considerable room for
      improvement in the current prohibitive approach to commercialism and organ
      trafficking. The Custodian Group and World Health Organization (WHO) should
      address commercialism by encouraging the expansion of living donation in the same
      manner as they encourage deceased donation. Furthermore, the Custodian Group and
      the WHO can improve their strategy to combat organ trafficking by raising
      awareness for enforcement. To achieve a consistent and effective prohibition of
      trafficking, legislation and law enforcement must go hand in hand. Ideally, this
      can best be achieved by close collaboration between the medical field and
      (international) criminal justice agencies.

PMID- 22150957
TI  - Diagnostic yield of bronchoscopic sampling in febrile neutropenic patients with
      pulmonary infiltrate and haematological disorders.
AB  - BACKGROUND: The development of pulmonary infiltrate in neutropenic patients is
      potentially life-threatening, and requires early diagnosis and treatment.
      Bronchoscopic sampling is an established form of investigation in such patients.
      AIM: The aim of the study is to determine the diagnostic yield and complication
      rate of bronchoscopic sampling in patients with a haematological disorder
      presenting with febrile neutropenia and pulmonary infiltrate. METHODS: Medical
      records and laboratory investigations were retrospectively reviewed for all
      patients with a haematological disorder who underwent flexible bronchoscopy and
      bronchoalveolar lavage (BAL) or bronchial washing (BW) at Auckland City Hospital,
      New Zealand, after presenting with febrile neutropenia and pulmonary infiltrate
      between January 2008 and December 2009. Demographic, clinical, radiological and
      microbiological data, procedure-related complications and treatment were
      recorded. Modifications to treatment regimens as a result of bronchoscopy and 30
      day mortality were recorded. RESULTS: Out of 678 bronchoscopies performed during
      this period, 26 were in patients with a haematological disorder presenting with
      febrile neutropenia and pulmonary infiltrate. Most patients had a haematological
      malignancy (19/26). Two (7.7%) patients reported minor haemoptysis. No biopsies
      were performed. Positive microbiological samples were obtained with BAL/BW in 23%
      of patients. The most common organisms identified were Aspergillus species
      (15.4%); other organisms were Candida (11.6%) and Streptococcus pneumoniae
      (3.9%). The bronchoscopic results altered the clinical management of 10 (38.4%)
      patients. The 30-day mortality rate was 19.2%, but no deaths were related to the
      procedure. CONCLUSIONS: In haematology patients presenting with febrile
      neutropenia and pulmonary infiltrate, bronchoscopy is a safe procedure that plays
      a significant role in management.

PMID- 22150958
TI  - Assessment of central adrenal insufficiency in children and adolescents with
      Prader-Willi syndrome.
AB  - OBJECTIVE: A recent study evidenced by metyrapone test a central adrenal
      insufficiency (CAI) in 60% of Prader-Willi syndrome (PWS) children. These results
      were not confirmed in investigations with low [Low-Dose Tetracosactrin
      Stimulation Test (LDTST), 1 MUg] or standard-dose tetracosactrin stimulation
      tests. We extended the research by LDTST in paediatric patients with PWS. DESIGN:
      Cross-sectional evaluation of adrenal stress response to LDTST in a PWS cohort of
      a tertiary care referral centre. PATIENTS: Eighty-four children with PWS.
      MEASUREMENTS: Assessment of adrenal response by morning cortisol and ACTH dosage,
      and 1-MUg tetracosactrin test. Response was considered appropriate when cortisol
      reached 500 nm; below this threshold, patients were submitted to a second test.
      Responses were correlated with the patients' clinical and molecular
      characteristics to assess genotype-phenotype correlation. RESULTS: Pathological
      cortisol peak responses to the LDTST were registered in 12 patients (14.3%) who
      had reduced basal (169.4 +/- 83.3 nm) and stimulated (428.1 +/- 69.6 nm) cortisol
      levels compared to patients with normal responses (367.1 +/- 170.6 and 775.9 +/-
      191.3 nm, P < 0.001). Body mass index standard deviation score was negatively
      correlated with basal and peak cortisol levels (both P < 0.001), and the
      patients' ages (P < 0.001). In patients with deletion on chromosome 15, the
      cortisol peak was significantly lower than that in uniparental disomy (UPD) cases
      (P = 0.030). At multiple regression analysis, the predictors of peak response
      were basal cortisol, age, and UPD subclass (r(2) = 0.353, P < 0.001). Standard
      dose (250 MUg) tetracosactrin test confirmed CAI in 4/12 patients (4.8% of the
      cohort). CONCLUSIONS: Our results support the hypothesis that, albeit rare, CAI
      may be part of the PWS in childhood.

PMID- 22150959
TI  - Transcatheter closure of a large atrial septal defect under microprobe
      transesophageal echocardiographic guidance.
AB  - We present a case of an atrial septal defect (ASD) in a 59-year-old man with an
      indication for ASD closure who also had a history of chronic obstructive
      pulmonary disease. Because of his decreased respiratory function with multiple
      bullae in his lungs, the procedure was performed without general anesthesia under
      the guidance of fluoroscopy and two-dimensional (2D) transesophageal
      echocardiography (TEE) using a transesophageal echocardiographic microprobe
      (micro-TEE) (S8-3t; Philips Medical Systems, Andover, MA, USA). The micro-TEE
      probe was inserted into the esophagus smoothly and easily in the supine position
      without sedation. It revealed a deficient superior-anterior rim and adequate rims
      elsewhere, and the maximal diameter of ASD was measured to be 25 mm. Balloon
      sizing resulted in a stretched defect diameter of 29 mm using the stop-flow
      technique. A 30-mm AMPLATZER Septal Occluder (AGA Medical, Plymouth, MN, USA) was
      deployed. The micro-TEE demonstrated that both disks were on the appropriate
      sides of the interatrial septum and the device was not interfering with surround
      cardiac structures. Residual shunt flow was not detected with color Doppler. The
      device was released successfully without any complications. Recently introduced
      multiplane micro-TEE can provide adequate information about a large ASD with a
      less invasive procedure in adult patients. Micro-TEE has a potential to become a
      novel imaging option for interventions of the interatrial septum.

PMID- 22150960
TI  - Effect of different photoperiods and melatonin treatment on rabbit reproductive
      performance.
AB  - BACKGROUND: Rabbit production in Egypt exhibits a seasonal pattern with much
      higher yields from September to May. This variation might be explained by
      reproductive performance as controlled by annual photoperiodicity.
      HYPOTHESIS/OBJECTIVES: The aim of this study was to investigate whether the
      reproductive performance of rabbits can be improved by either increasing the
      photoperiod or by administering melatonin supplement. ANIMALS AND METHODS: In
      total 78 White New Zealand rabbits (60 does and 18 bucks) were used during
      September and October reared in a private Rabbitary in Menuofia Governorate,
      Egypt. The animals were randomly assigned to six treatment groups of 10 does and
      three bucks each (8, 10, 12, 14, and 16 h light and melatonin (1 mg/kg BW/day
      orally for two weeks). Ejaculate traits, sexual activity of bucks, sexual
      receptivity and reproductive performance of does were recorded. RESULTS: The
      results revealed that exposure of rabbits to long photoperiods (14 and 16 h
      light) or treatment with melatonin improved the quantity and quality of ejaculate
      traits and buck sexual activity as well as doe's sexual receptivity, feed intake,
      litter size, weight at birth and time-to-weaning. On the other hand, gestation
      period and pre-weaning mortality percentage decreased. CONCLUSIONS: Application
      of long photoperiods is beneficial to rabbit producers and 14 h light combined
      with 10 h dark is optimal for satisfying the physiological requirements of the
      rabbits. Finally, from an economic point of view, the light schedules are cheap
      and easy to apply and can be used as biostimulation instead of melatonin.

PMID- 22150961
TI  - Familial eruptive vellus hair cysts.
AB  - Eruptive vellus hairs cysts are benign papules consisting of small cysts
      containing multiple vellus hairs. An eruption commonly develops on the chest and
      sometimes the upper extremities. These papules are asymptomatic or rarely
      pruritic. Only a few cases of familial association have been described. We report
      the development of eruptive vellus hair cysts on the trunk of an 8- and 12-year
      old sister and brother.

PMID- 22150962
TI  - Acceptance of insulin therapy: a long shot? Psychological insulin resistance in
      primary care.
AB  - AIM: To explore which factors are associated with psychological insulin
      resistance in insulin-naive patients with Type 2 diabetes in primary care.
      METHODS: A sample of 101 insulin-naive patients with Type 2 diabetes completed
      self-administered questionnaires including demographic and clinical
      characteristics, the Insulin Treatment Appraisal Scale and the Center for
      Epidemiological Studies Depression scale. Psychological insulin resistance was
      denoted by negative appraisal of insulin (Insulin Treatment Appraisal Scale).
      RESULTS: Thirty-nine per cent of the sample were unwilling to accept insulin
      therapy. Unwilling participants perceived taking insulin more often as a failure
      to control their diabetes with tablets or lifestyle compared with willing
      participants (59 vs. 33%), unwilling participants were more reluctant to accept
      the responsibilities of everyday management of insulin therapy (49 vs. 24%).
      Multiple linear regression analysis revealed that depression and objection to
      lifelong insulin therapy were independently associated with psychological insulin
      resistance. CONCLUSIONS: In this study in primary care, depression and objection
      to lifelong insulin therapy are associated with psychological insulin resistance.
      Analysis of the objection to the indefiniteness of insulin therapy showed a sense
      of limitation of daily life and loss of independence that should not be
      underestimated. Insulin should be offered as a means to improve health as this
      might facilitate the acceptance of insulin therapy.

PMID- 22150963
TI  - Electrodermal lability as an indicator for subjective sleepiness during total
      sleep deprivation.
AB  - The present study addresses the suitability of electrodermal lability as an
      indicator of individual vulnerability to the effects of total sleep deprivation.
      During two complete circadian cycles, the effects of 48h of total sleep
      deprivation on physiological measures (electrodermal activity and body
      temperature), subjective sleepiness (measured by visual analogue scale and
      tiredness symptom scale) and task performance (reaction time and errors in a
      go/no go task) were investigated. Analyses of variance with repeated measures
      revealed substantial decreases of the number of skin conductance responses, body
      temperature, and increases for subjective sleepiness, reaction time and error
      rates. For all changes, strong circadian oscillations could be observed as well.
      The electrodermal more labile subgroup reported higher subjective sleepiness
      compared with electrodermal more stable participants, but showed no differences
      in the time courses of body temperature and task performance. Therefore,
      electrodermal lability seems to be a specific indicator for the changes in
      subjective sleepiness due to total sleep deprivation and circadian oscillations,
      but not a suitable indicator for vulnerability to the effects of sleep
      deprivation per se.

PMID- 22150964
TI  - The performance and safety of an implantable spinal cord stimulation system in
      patients with chronic pain: a 5-year study.
AB  - Reliability and ease of use of the Itrel 3 System (Medtronic Inc., Minneapolis,
      MN) were prospectively assessed over 5 years in patients with a range of pain
      syndromes (mainly low back and/or leg pain, or ischemic pain due to peripheral
      vascular disease). The longevity of the implantable pulse generator (IPG)
      battery, the frequency with which system settings were changed, and the ease of
      use of the EZ patient programmer were assessed. Data on adverse events, pain
      relief, and patient satisfaction with therapy were also collected. Following a
      screening procedure, 85 systems were implanted in 84 patients. Twenty-four
      patients were withdrawn prematurely and, in an additional 32 cases, end of
      battery life was reached before the end of the study. The survival curve for the
      IPG batteries showed that approximately 50% are expected to last up to the sixth
      year. No device failures or unanticipated device-related adverse events were
      reported. At least 90% of patients considered the EZ patient programmer easy to
      use. System settings were stable over time. The intensity and duration of pain
      were reduced significantly and patient satisfaction with therapy was high. We
      conclude that the Itrel 3 System performed well over 5 years and was easy to use.
      Its safety and effectiveness for the relief of chronic intractable pain of the
      trunk or limbs were also confirmed.

PMID- 22150965
TI  - Possible stabilization of spinal cord stimulation treatment in refractory angina
      pectoris by implantation of a second electrode: case reports.
AB  - Patients with refractory angina pectoris usually exhaust conventional treatment
      of ischemic heart disease. They frequently need opioids and still have angina
      pectoris despite earlier coronary artery bypass grafting (CABG) or percutaneous
      coronary intervention (PCI). In those cases, treatment strategies including
      neuromodulation techniques such as transcutaneous electrical neurostimulation
      (TENS) or spinal cord stimulation (SCS) often are successful. Covering the pain
      area with electrically induced paraesthesia leads to a reduction in angina
      incidence, reduced opioid and nitrate consumption, better results under stress
      test, and better quality of life. A rare complication in treatment of refractory
      angina pectoris with SCS is repeated electrode displacement. We report three
      cases where the problem was solved with the implantation of a dual electrode
      system. After a period with TENS, patients suffering from refractory angina
      pectoris are normally treated with implantation of a single electrode SCS-system.
      Presently over 130 devices have been implanted for this indication at our
      hospital. In three patients, repeated electrode displacement occurred, and
      despite the attempt to replace the electrode, it was impossible to provoke
      sufficient paraesthesia in the pain area. These patients were offered the
      implantation of a dual electrode system where two electrodes are placed in the
      epidural space. With the dual electrode system, good and stable stimulation was
      achieved, provoking appropriate paraesthesia. This suggests that two electrodes
      implanted in the epidural space may stabilize each other mechanically. On the
      other hand the variety of program adjustments is enlarged, due to the additional
      poles on the second electrode. On the basis of these case reports, we suggest
      that implantation of a dual electrode SCS-device might be the solution in case of
      repeated displacement of a single SCS-electrode.

PMID- 22150966
TI  - Pont de dolor: a dual laminotomy technique for placing and securing an electrode
      in the epidural space and comments about anatomic variation that may complicate
      spinal cord stimulator electrode placement.
AB  - The objective of this report is to describe a surgical technique used
      successfully when a flat or paddle type spinal cord stimulator electrode cannot
      be properly positioned via a single laminotomy. Different and innovative surgical
      techniques useful in placement of spinal cord stimulators and analgesic infusion
      pump systems have not been well described. The prevalence of anatomic surgical
      abnormalities or variations that might present barriers to implantation of these
      devices is unknown but may be as high as 18% for revisions. A dual laminotomy
      technique can be useful and successful in positioning a flat spinal cord
      stimulator electrode that cannot be properly positioned via a single laminotomy
      approach. We report two patients who have been treated successfully with a dual
      laminotomy technique.

PMID- 22150967
TI  - Task-dependent modulation of visuospatial exploration by transcutaneous
      electrical neural stimulation and cyclic pressure application.
AB  - We investigated the effects of one somatosensory stimulation technique, the
      cyclic pressure application (CPA), and compared them with the effects of left
      transcutaneous electrical stimulation (TENS) on the expression of left
      visuospatial exploration deficits in 13 stroke patients, as assessed by four
      visuospatial exploration tasks. Four treatment conditions were given: TENS, CPA,
      TENS + CPA, as well as a placebo condition. For each patient, the intensity of
      the TENS was determined, based on his/her perception threshold of paresthesia for
      the electrical impulses. The results demonstrated that only TENS stimulation is a
      sufficient condition to reduce the expression of visuospatial exploration
      deficits dependent of the task. The point of time at which stimulation had an
      effect was also dependent of the mode of stimulation and the task. Normal
      visuomotor integration requires the ability to explore both sides (left and
      right) of the visual space with egocentric reference to the midsagittal plane of
      trunk. Unilateral disturbances in visuospatial exploration, often associated with
      the neurologic syndrome of hemispatial neglect and more frequently observed after
      right hemisphere damage, refers to the defective ability of patients with
      unilateral cerebral lesions to explore the side of space contralateral to the
      lesion. Many quantifiable tests have been developed to assess the expression of
      visuomotor exploration. These tests differ substantially in their sensitivity,
      but the Star Cancellation and Line Bisection tasks are cited as the most
      sensitive measurements of visuospatial exploration.

PMID- 22150968
TI  - The Effects of TENS, Heat, and Cold on the Pain Thresholds Induced by Mechanical
      Pressure in Healthy Volunteers.
AB  - This study was aimed to test whether the administration of transcutaneous
      electrical neural stimulation (TENS), heat or cold alone, or the coadministration
      of TENS in combination with heat or with cold may alter the thresholds of the
      sensory (algosity) and the affective (unpleasantness) dimensions of experimental
      pain. Mechanical pain induced by a pressure algometer was applied to the tibial
      shaft of 180 healthy volunteers before and after random application of one of the
      six following modalities: sham-stimulation, cold, heat, TENS, combination of TENS
      + cold, or combination of TENS + heat. All modalities were applied in the same
      (L4) dermatome with the use of Thermotens (Mediseb Technologies Ltd., Hertzelia,
      Israel), a device which produces quantifiable combinations of thermal and
      electrical modalities separately or simultaneously. Only the combination of TENS
      + heat significantly elevated the thresholds of algosity (from 221 mmHg to 262
      mmHg, p < 0.01) and of unpleasantness (from 134 +/- 9 to 197 +/- 9 mmHg; p <
      0.001). These findings suggest that the coadministration of several physical
      modalities can be more efficacious in the treatment of pain than each modality
      alone.

PMID- 22150969
TI  - Robotic orthosis lokomat: a rehabilitation and research tool.
AB  - The aim of this article is to introduce the robotic orthosis Lokomat, developed
      to automate treadmill training rehabilitation of locomotion for spinal cord
      injured and stroke patients, to the Functional Electrical Stimulation (FES) and
      Neuromodulation research communities, and to report on our newly conducted
      research. We first illustrate the primary use of Lokomat in rehabilitation and
      focus on control aspects and algorithms associated with robotic rehabilitation of
      locomotion. Then we describe two applications where the Lokomat was used as a
      research tool. The first application is closed-loop control of the FES-induced
      shank movement and the second is the development of a neural network model of the
      spinal locomotor centers. This model was used to derive a neural locomotion
      controller for the Lokomat.

PMID- 22150970
TI  - A Fast Passive Data Transmission Method for ENG Telemetry.
AB  - The objective of this study was to develop a high bit-rate passive method for
      conveying ENG signals from implants which would work over a wide range of
      coupling coefficients. A novel method, Passive Phase Shift Modulation, was
      studied in theory, by simulation, and implemented in the laboratory. A binary
      signal of 222 kbit/s was passed on a 4-MHz carrier (ratio 1:18) with coil-coil
      spacings up to 70 mm (coil diameters are 45 and 60 mm) with an addition to the
      power consumption equivalent to 2 mW in the implant. We conclude that this is a
      satisfactory method to be used as part an implant for conditional neuromodulation
      that we are designing.

PMID- 22150971
TI  - FES Gait Re-education: The Swing Phase Estimation.
AB  - This paper presents the use of multiple sensors for walking assessment and
      provision of cognitive feedback during early re-education of incomplete spinal
      cord injured (SCI) humans. The paper is focused on the swing phase estimation as
      an important part of the Functional Electrical Stimulation (FES) gait re
      education system for incomplete spinal cord injured persons. The proposed sensory
      system comprises four accelerometers, one gyro placed at the shank of the paretic
      leg, and two goniometers placed at the knee and ankle joints, respectively. The
      data from the sensors are input in the mathematical algorithm applied for swing
      quality estimation. The output from the algorithm is a numerical value. The
      calculated output is divided into three levels, each defining the swing quality
      in terms of good, sufficient, and poor. This information is provided to the
      patient as an auditory signal. The patient is taught to maximize his efforts to
      improve the quality of walking, that is, to move the more affected leg in a way
      that will generate the auditory output corresponding to the level "good".  The
      preliminary measurements were performed in healthy subjects walking on even
      terrain and in an incomplete SCI person with C6 lesion during walking on the
      treadmill. FES in the latter case was triggered manually by a physiotherapist.
      The results showed that the timing of FES triggering played an important role in
      sensory-supported FES-assisted walking, that is, the auditory feedback was also a
      cue to the therapist controlling the FES. The swing quality estimation enabled
      patients to voluntarily improve their walking, consequently the intensity of FES
      assistance was decreased. This suggests that the use of an FES multisensor system
      for cognitive feedback is efficient rehabilitative method in early stage of
      rehabilitation of walking.

PMID- 22150972
TI  - Cost benefit of radio frequency linked spinal cord stimulation.

PMID- 22150973
TI  - Reply.

PMID- 22150974
TI  - Prognostic significance of cyclinD1 amplification and the co-alteration of
      cyclinD1/pRb/ppRb in patients with esophageal squamous cell carcinoma.
AB  - CyclinD1/pRb/ppRb is one of the most important pathways regulating the cell
      cycle, and related with the development of many cancers. However, the co
      alteration of CyclinD1/pRb/ppRb in esophageal squamous cell carcinomas is less
      understood. This study aims to analyze the combined prognostic significance of
      cyclinD1 (CCND1) DNA amplification and the co-alteration of CCND1/pRb/ppRB in
      patients with esophageal squamous cell carcinoma. CCND1 DNA amplification and the
      protein expression of CCND1, pRb, and ppRb on 100 tumor specimens and 11 normal
      tissues were detected using real-time quantitative reverse transcription
      polymerase chain reaction and immunohistochemistry, respectively. Their prognosis
      significance was analyzed by Kaplan-Meier method. We found that 41% of the
      patients had CCND1 DNA amplification, which had a short survival time compared
      with the patients without CCND1 amplification (25.63 months vs. not reached,
      P=0.007). The patients with the co-alternation of CCND1(+) /pRb(-) /ppRb(+)
      protein expression levels have a poorer overall survival than the others (11.4
      vs. 43.4 months, P=0.001). Cox regression analysis showed that the co-alternation
      of CCND1/pRb/ppRb and CyclinD1 amplification were the two most independent
      prognosis factors of patients with esophageal cancer. These findings suggested
      that CCND1 amplification and co-alternation of CCND1(+) /pRb(-) /ppRb(+) may play
      a crucial role in the prognostic evaluation of patients with esophageal cancer,
      and the patients with CCND1(+) /pRb(-) /ppRb(+) have the worst prognosis in all
      the patients. The results also indicated that the patients with CCND1
      amplification or co-alternation of CyclinD1(+) /pRb(-) /ppRb(+) might be the
      preponderant people for therapy targeting the CCND1/pRb/ppRb pathway in the
      future.

PMID- 22150975
TI  - The impact of antibiotic use on the incidence and resistance pattern of extended
      spectrum beta-lactamase-producing bacteria in primary and secondary healthcare
      settings.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * The emergence and spread of bacteria
      producing extended-spectrum beta-lactamases (ESBLs) has important therapeutic and
      epidemiologic implications. * A key target for the establishment of hospital
      antibiotic stewardship is reducing the occurrence of additional antibiotic
      resistance. * Further research is needed to accumulate supporting evidence that
      reducing antibiotic use will result in a parallel reduction in antibiotic
      resistance. WHAT THIS STUDY ADDS: * Fluoroquinolone restriction reversed
      ciprofloxacin resistance in primary and secondary healthcare settings. *
      Fluoroquinolone restriction reduced ESBL-producing bacteria incidence rates in
      both the primary and secondary healthcare settings. * This study highlights the
      value of time-series analysis in designing efficient antibiotic stewardship.
      AIMS: The objective of the present study was to study the relationship between
      hospital antibiotic use, community antibiotic use and the incidence of extended
      spectrum beta-lactamase (ESBL)-producing bacteria in hospitals, while assessing
      the impact of a fluoroquinolone restriction policy on ESBL-producing bacteria
      incidence rates. METHODS: The study was retrospective and ecological in design. A
      multivariate autoregressive integrated moving average (ARIMA) model was built to
      relate antibiotic use to ESB-producing bacteria incidence rates and resistance
      patterns over a 5 year period (January 2005-December 2009). RESULTS: Analysis
      showed that the hospital incidence of ESBLs had a positive relationship with the
      use of fluoroquinolones in the hospital (coefficient = 0.174, P= 0.02),
      amoxicillin-clavulanic acid in the community (coefficient = 1.03, P= 0.03) and
      mean co-morbidity scores for hospitalized patients (coefficient = 2.15, P= 0.03)
      with various time lags. The fluoroquinolone restriction policy was implemented
      successfully with the mean use of fluoroquinolones (mainly ciprofloxacin) being
      reduced from 133 to 17 defined daily doses (DDDs)/1000 bed days (P < 0.001) and
      from 0.65 to 0.54 DDDs/1000 inhabitants/day (P= 0.0007), in both the hospital and
      its surrounding community, respectively. This was associated with an improved
      ciprofloxacin susceptibility in both settings [ciprofloxacin susceptibility being
      improved from 16% to 28% in the community (P < 0.001)] and with a statistically
      significant reduction in ESBL-producing bacteria incidence rates. DISCUSSION:
      This study supports the value of restricting the use of certain antimicrobial
      classes to control ESBL, and demonstrates the feasibility of reversing resistance
      patterns post successful antibiotic restriction. The study also highlights the
      potential value of the time-series analysis in designing efficient antibiotic
      stewardship.

PMID- 22150976
TI  - Editorial.

PMID- 22150977
TI  - Comments from the editor for spinal disorders.

PMID- 22150978
TI  - Intrathecal administration of different drugs by programmable infusion device in
      chronic pain. A case report.
AB  - Objective and Importance. The subarachnoid infusion of narcotics by programmable
      devices in patients with chronic non-malignant pain can be a useful therapeutic
      method. However, certain side-effects, opioid tolerance or changes in the nature
      of the pain can lead to failure of the therapy. Clinical Presentation. We present
      a case report of a woman with both chronic perineal pain and sciatic pain with
      radiation to her lower limbs caused by failed back surgery syndrome. The pain
      proved to be resistant to common medical therapy and to spinal cord stimulation.
      Technique. After surgical implantation of a programmable infusion pump, the
      patient's leg pain improved with an intrathecal infusion of morphine and
      bupivacaine. The perineal pain was treated with an infusion of clonidine. The
      patient therefore needed alternative infusions of both drugs with changes of
      infusional parameters. Conclusion. The possibility of varying the infusion method
      of mixed drugs or alternating the drugs is fundamental for successful therapy
      since neuropathic pain must be considered a dynamic state.

PMID- 22150979
TI  - Long-Term Intrathecal Infusion of Opioid and/or Bupivacaine in the Prophylaxis
      and Treatment of Phantom Limb Pain.
AB  - Introduction and Methods. A prospective, open case study was performed on 37
      patients, given intrathecal (IT) bupivacaine alone or bupivacaine/opioid
      combinations for refractory pain located in the extremities to explore the
      potential of this therapy for prophylaxis against post-amputation pain (PLP)
      and/or the treatment of severe, established PLP. Intrathecal infusions were
      administered before, during, and after amputation, as an attempt to prevent PLP
      ("prophylaxis group"; n = 21), or to relieve existing severe PLP after previous
      amputations ("treatment group"; n = 16). Results. All patients but one in the
      prophylaxis group obtained 60-100% pain relief during intrathecal therapy.
      Systemic daily doses of opioid decreased approximately threefold from pre
      intrathecal therapy, analgesic/sedative consumption was reduced by 50% and
      nocturnal sleep duration improved from 2-4 h to 6-8 h post intrathecal therapy.
      During post-amputation IT treatment, transient PLP of less than 1 day duration
      and/or phantom limb sensation (PLS) occurred in 9 patients in the "prophylaxis
      group" and in 2 patients in the "treatment group." 4 out of 16 patients (25%) in
      the prophylactic group and 0 out of 10 (0%) in the treatment group presented
      neither PLP nor PLS after termination of the IT treatment. Conclusions.
      Continuous IT infusion of bupivacaine with or without opioid gave satisfactory
      pain relief during the treatment in 95% of the patients. Continuous IT infusion
      of bupivacaine, alone or in combination with opioid, relieved severe preexisting
      PLP during the treatment in 100% of the treated patients, but did not prevent its
      recurrence after the end of the intrathecal treatment.

PMID- 22150980
TI  - Spinal geometry and paresthesia coverage in spinal cord stimulation.
AB  - Objective. To test the following hypotheses, based on computer modeling studies
      of spinal cord stimulation, by the analysis of data from chronic pain patients:
      I. the probability-of-paresthesia in a dermatome is highest when the cathode is
      placed at the corresponding segmental level; II. variation of the rostrocaudal
      position of the cathode in the lower cervical/high thoracic region results in
      less variation of the probability-of-paresthesia in a dermatome than stimulation
      in more caudal regions; III. when stimulating in the midthoracic region, the
      probability-of-paresthesia in a dermatome is low in comparison to other regions
      when the cathode is not at the corresponding segmental level. Method. The
      probability-of-paresthesia in 16 body segments as a function of the rostrocaudal
      position of the cathode was analyzed from the paresthesia coverage with 3,897
      bipolar and unipolar combinations from 106 chronic pain patients. Results. The
      distributions of the probability-of-paresthesia in the upper and lower limb are
      in accordance with the hypotheses, but different distributions were found in all
      trunk areas. Conclusion. The success to be expected from spinal cord stimulation
      in chronic pain management is inversely related to the thickness of the dorsal
      cerebrospinal fluid layer at the cathode level. Therefore, preoperative
      measurement from transverse images can be helpful as a predictor for success.

PMID- 22150981
TI  - Neurologic sequelae of intraspinal drug delivery systems: results of a survey of
      american implanters of implantable drug delivery systems.
AB  - OBJECTIVES. The development of neurological sequelae subsequent to the placement
      of intraspinal drug delivery systems is particularly distressing. An attempt was
      made to determine the extent of this problem in both reported and in heretofore
      unreported cases. Methods. A survey was mailed to 3269 implanters of intraspinal
      infusional systems to identify new cases of neurological sequelae of pump
      Implantation. 519 out of 3269 surveys mailed out responded. Results. There were
      488 "no" respondents and 31 "yes" respondents to the question: "did any patient
      of yours develop neurologic sequelae or granulomatous catheter mass formation
      after implant of their intraspinal catheters?" 6 new, heretofore unreported cases
      of granulomatous mass formations at catheter tips were reported. 27 cases of
      neurological sequelae due to other etiologies were also noted. Also presented in
      this paper are 4 case reports to augment reader understanding of the problem.
      Conclusions. The problem of post-implant neurological sequelae is potentially
      devastating. Increased vigilance for early diagnosis may prevent the development
      of permanent paralysis. Gadolinium enhanced MRI scanning at the catheter tip is
      the imaging study of choice for diagnosis. Any patient developing a new area of
      pain, weakness or rapid escalation in intrathecal drug dose should be thoroughly
      assessed.

PMID- 22150982
TI  - Use of Intraspinal Infusion Therapy with Non-Cancer Pain Patients: Follow-up and
      Comparison of Worker's Compensation vs. Non-Worker's Compensation Patients.
AB  - Objective. This study examines, in a retrospective fashion, the effects of
      intraspinal infusion therapy in 36 patients with pain of non-cancer origin. In
      those cases where pain was recalcitrant to the infused opiate and/or had a
      neuropathic component, a local anesthetic, tetracaine, was added. Patients were
      followed for a minimum of 16 months (average 20.17 months). Data were collected
      from the patient, office records, and significant others regarding changes in
      pain, functioning, work, and oral narcotic use. Telephone interviews were
      conducted by a disinterested third party. A comparison of worker's compensation
      (WC) and non-worker's compensation (NWC) patients was made. Results. An average
      of 60.8% subjective improvement in pain and a 76.7% decrease in use of oral
      medications were shown. The average reported percentage improvement in
      functioning was 47.8%. Over 83% of patients rated the outcome of intraspinal
      infusion therapy as "good or excellent," but only 59.4% of significant others did
      so. No statistically significant differences were observed between the WC and NWC
      groups on 10 of 11 dependent variables, with the exception of change in
      functioning. The addition of tetracaine did not decrease the opiate requirement
      but appeared to contribute to analgesia. Nausea was the single most drug-related
      complaint. Twelve patients (33%) encountered catheter complications requiring
      surgical intervention. Three patients had the drug administration system (DAS)
      removed for a variety of reasons. There were no documented mechanical failures.
      Conclusion. The results support the potential utility of infusion therapy in the
      treatment of non-cancer pain. This treatment, however, is not without problems
      and should be applied judiciously and in the context of evolving guidelines.

PMID- 22150983
TI  - To the editor.

PMID- 22150984
TI  - Reply.

PMID- 22150985
TI  - Multiple-cell spike density and neural noise level analysis by semimicroelectrode
      recording for identification of the subthalamic nucleus during surgery for
      Parkinson's disease.
AB  - Objective.   For targeting the subthalamic nucleus (STN), we attempted to
      quantify the changes in multiple cell activities by computing the neural noise
      level and multiple-cell spike density (MSD). Methods.   We analyzed the neural
      noise level and MSD by stepwise recording at every 0.25-mm increment during the
      final tracking in 90 sides of 45 patients with Parkinson's disease. The MSD was
      analyzed with cut-off levels ranging from 1.2- to 2.0-fold the neural noise level
      in the internal capsule or zona incerta in each trajectory. Results.   The dorsal
      boundary of the STN was identified from an increase in the neural noise ratio in
      all sides. The ventral boundary was identifiable, however, from a decrease in the
      neural noise ratio in only 70 sides (78%). In contrast, both the dorsal and
      ventral boundaries were clearly identified from an increase and a decrease in the
      MSD, respectively, in all of the 90 sides. Conclusion.   MSD analysis by
      semimicroelectrode recording represents a useful, practical, and apparently
      reliable means for identifying the boundaries of the STN.

PMID- 22150986
TI  - Imaging of the subthalamic nucleus for deep brain stimulation: a systematic
      review.
AB  - It is still debated which neuroimaging technique should be preferred in targeting
      the subthalamic nucleus (STN) for implantation of stimulating electrodes. In the
      present study, we systematically analyzed the different imaging techniques and
      their outcome in reports describing original data on bilateral STN stimulation in
      advanced Parkinson's disease. Five different imaging techniques to target the STN
      for implantation of stimulating electrodes were reported: magnetic resonance
      imaging (MRI), MRI in combination with ventriculography, MRI in combination with
      computed tomography (CT), CT, and CT in combination with ventriculography. We
      found that patients who underwent STN deep brain stimulation with MRI (regardless
      the use of an additional imaging technique) had a significantly better Unified
      Parkinson's Disease Rating Scale motor score (mean improvement 58%) as compared
      to patients who underwent STN deep brain stimulation with CT imaging (regardless
      the use of an additional imaging technique; mean improvement 47%).

PMID- 22150987
TI  - The human nucleus accumbens: where is it? A stereotactic, anatomical and magnetic
      resonance imaging study.
AB  - Objectives.   Identification, delimitation, and stereotactic localization of the
      human nucleus accumbens (Acc) in order to allow its accurate definition and three
      dimensional targeting on magnetic resonance imaging (MRI) enabling its use for
      deep brain stimulation. Methods.   Magnetic resonance imaging and anatomical
      coronal serial cuts were performed on 24 Acc from human cadaver brains
      perpendicular to the anterior commissure-posterior commissure line;
      identification, localization, and determination of its dimensions and three
      dimensional stereotactic coordinates. Results.   Twenty Acc were studied
      anatomically, 14 by MRI and 12 by both methods. The contours of the Acc were
      traced and the dimensions measured; mean values: length 10.5 mm, width 14.5 mm
      and height 7.0 mm. The stereotactic coordinates were obtained every millimeter
      along its length. Conclusion.   It was possible to identify well the human Acc,
      define its limits and establish its three-dimensional coordinates as potential
      MRI-guided stereotactic target.

PMID- 22150988
TI  - The correlation between cytokine production by cerebral cortical glial cells and
      brain lateralization in mice.
AB  - Objectives.   This study aims to explore the relationship among the levels of
      interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha)
      produced by cortical glial cells, and identify any correlation between
      neuromodulation and brain lateralization. Material and Methods.   Cortical glial
      cells from Balb/c neonatal mice were cultured in vitro and the effects of
      treating or not treating these cells from both hemispheres with
      lipopolysaccharide (LPS) (10 ug/mL) for 24 hours were tested. The levels of IL
      1beta, IL-6, and TNF-alpha in left and right cortical glial cell cultures and the
      time course of any changes were compared. Rusults.   The production of IL-1beta
      and TNF-alpha had no significant difference between right and left cortex in the
      untreated group within 24 hours. IL-6 was significantly higher in the right than
      the left cortical glial cells. In the LPS-treated group, increased levels of IL
      1beta, TNF-alpha, and IL-6 were found, particularly for IL-6, and all were
      significantly increased in cortical glia cells from the right side. The time
      course shows that the expression of IL-1beta in right cortex and IL-6 in both
      sides is time-dependent (p < 0.05). Conclusion.   Lipopolysaccharide increases
      cytokine production in both cerebral cortices, three cytokines have different
      expression time course within 72 hours, but only IL-1beta in right cortex and IL
      6 releasing is time-dependent, and more so on the right side than the left in 24
      hours. We proposed the increased immunosuppressive activity of right cortex was
      due to the higher expression of IL-1beta, TNF-alpha, and IL-6 in the right
      cortical glial cells, whereas there would be more immunoenhancement activity of
      the left cortex due to the lower levels of these three kinds of cytokines, this
      being a less pronounced effect than that on the right side. One of the reasons
      for the brain lateralization may be the different production of cytokines by the
      cortical glial cells on either side.

PMID- 22150989
TI  - Implantable intrathecal pumps for the treatment of noncancer chronic pain in
      elderly population: drug dose and clinical efficacy.
AB  - Objective.   This study aims to assess long-term follow-up of efficacy and
      quality of life for 34 geriatric patients (10 men, 24 women, mean age 72.3 +/-
      11.6 years) with intrathecal (IT) drug delivery systems (IDDS), implanted between
      1994 and 2002, for the treatment of severe noncancer chronic pain. Methods.  
      Patients equal to or older than 64 years, who had no pain relief after
      administration of a placebo injection (subcutaneous saline), and who responded
      positively to an IT trial (morphine and bupivacaine at low doses) with pain
      relief greater 70% without intolerable adverse effects were included into our
      study. Clinical assessment forms and questionnaires assessing pain intensity,
      adverse events, complications, concommitent use of analgesics, and doses of IT
      drugs administered were filled out by our patients prior to and after IT drug
      delivery implantation. Results.   Pain intensity was substantially reduced (60%)
      at three-month follow-up after commencing IT therapy and was consistently reduced
      at 48-month follow-up. The mean visual analog scale (VAS) value decreased from
      8.09 (+/- 1.25) before implantation to 1.68 (+/- 0.63) after implantation at 48
      month follow-up. This benefit, at 48 months, was achieved using mean low doses of
      IT morphine and bupivacaine, 1.03 +/- 0.61 mg and 1.15 +/- 0.58 mg, respectively.
      Only two out of 34 patients (5.9%) had complications related to the implantation
      procedure, itself. Side-effects of therapy were reported by 50% of the patients,
      the most frequent being constipation (34.4%), drowsiness (21.9%), nausea (21.9%),
      and urinary retention (18.8%). No side-effects of therapy resulted in removal of
      the IDDS. Conclusion.   The use of IT drug delivery through IDDS for the
      treatment of non-cancer- and cancer-related pain in geriatric patients is
      successful.

PMID- 22150990
TI  - Continuous Intrathecal Infusion of Ziconotide for Treatment of Chronic Malignant
      and Nonmalignant Pain Over 12 Months: A Prospective, Open-label Study.
AB  - Objectives.  This study aims to assess the safety and efficacy of long-term
      intrathecal (IT) ziconotide infusion. Materials and Methods.  In this prospective
      study, 155 patients with severe chronic pain (48 with malignant pain, 107 with
      nonmalignant pain) who had been responsive to short-term IT ziconotide in a
      double-blind, placebo-controlled study received long-term, open-label IT
      ziconotide monotherapy. Efficacy assessments included the mean percentage change
      on the visual analog scale of pain intensity from baseline in the study of
      origin; safety was monitored by adverse event (AE) reports, periodic laboratory
      tests, and vital sign measurements. Results.  At the last available observation,
      the visual analog scale of pain intensity scores had decreased by a mean of 36.9%
      from baseline in the short-term trial (N = 144; 95% CI: 30.1-43.7%; p < 0.0001).
      The mean IT ziconotide dose remained stable over 12 months in the 31 patients who
      participated in the study for >= one year. Ziconotide-related AEs were reported
      in 147 out of 155 patients (94.8%); 39.4% of patients discontinued treatment
      because of AEs, the majority of which were considered ziconotide related.
      Conclusions.  Ziconotide IT monotherapy provided patients with analgesia for 12
      months in this open-label study, with an acceptable benefit/risk profile and no
      evidence of tolerance.

PMID- 22150991
TI  - Effect of sacral neuromodulation on the spinal nociceptive reflex of patients
      with idiopathic overactive bladder.
AB  - Objectives.   Sacral root stimulation (SRS) is a technique to restore the
      idiopathic overactive bladder (IOB). However, its mechanism of action is yet to
      be elucidated. Hence, we studied whether SRS restored IOB through the mechanism
      of spinal neuromodulation. Materials and Methods.   Six IOB patients and 10
      healthy volunteers were included in the study. The spinal nociceptive reflex was
      used as the index of spinal excitability and was evoked by electrical stimulation
      at the foot, with recording at the ipsilateral tibialis anterior. Results.   IOB
      patients had increased spinal excitability to somatic nociceptive stimuli of the
      lower limbs. This spinal excitability decreased and bladder function improved
      after SRS, an effect that outlasted actual stimulation by at least 30 min.
      Conclusions.   Our results showed that spinal excitability was increased in
      response to somatic nociceptive afferents in IOB patients. SRS restored bladder
      function, at least, in part, through spinal neuromodulation.

PMID- 22150992
TI  - Stimulation ranges, usage ranges, and paresthesia mapping during occipital nerve
      stimulation.
AB  - Introduction.   Subcutaneous, occipital nerve stimulation has emerged as a
      potentially effective treatment modality for patients with refractory headache
      disorders. The purpose of this study was to document occipital stimulation
      characteristics in 10 patients status post implantation of an occipital nerve
      stimulator. Methods.   All possible electrode combinations were tested in each
      patient, and sensory threshold, discomfort threshold, and associated paresthesia
      maps were noted. Results.   Mean perception threshold was 1.07 V and mean
      discomfort threshold was 3.63 V. The associated paresthesia maps demonstrated
      that most patients felt stimulation as expected in the occipital regions;
      trigeminal distribution stimulation occurred but only in a minority of patients.
      Half of the patients experienced >= 50% reduction in headache frequency or
      severity. Conclusions.   These results should aid in clinical decision-making and
      manufacturing requirements for this modality; larger, prospective studies will be
      needed to determine the safety and efficacy of stimulation techniques for
      headache disorders.

PMID- 22150993
TI  - A case of successful treatment of neuropathic pain after a scapular fracture
      using subcutaneous targeted neuromodulation.
AB  - Subcutaneous targeted neuromodulation is one part of the wider new peripheral
      neuromodulation development in the treatment of neuropathic pain. Although it has
      not received wider acceptance, there are many reports in the literature of
      successful use of this technique.

PMID- 22150994
TI  - Successful long-term outcomes of spinal cord stimulation despite limited pain
      relief during temporary trialing.
AB  - Objectives.  In spinal cord stimulation (SCS) therapy, limited pain relief during
      the temporary trial period is generally considered to be predictive of poor long
      term benefit. To validate or refute this perception, the long-term outcomes of
      subjects who reported less than 50% pain relief during a temporary SCS trial were
      examined. Materials and Methods.  Twelve subjects with intractable pain underwent
      implantation of trial SCS systems. After a trial period in which they reported
      less than 50% pain relief, they each received a permanent SCS implant. Pain
      ratings and complications were tracked for 6-18 months. Results.  At the end of
      the temporary trial period, the average pain relief was 21%; no subject reported
      50% or better pain relief. More favorable outcomes were reported after activation
      of the permanent system, however. At all follow-up time points, at least a third
      of the subjects reported better than 50% pain relief, and the average pain relief
      varied over time between 44% and 83%. All complications were readily resolved and
      no subjects withdrew from the study. Conclusions.  Although SCS provided limited
      pain relief during the trial period, efficacy was more satisfactory after
      permanent implantation. Several subjects went on to experience nearly complete
      pain relief for up to 18 months (the maximum follow-up visit for study purposes),
      and no subject chose to discontinue SCS therapy. SCS appears to be a viable
      treatment option for patients who fail trials, raising some doubt as to the
      predictive sensitivity and specificity of the trial period. Thus, although
      outcome of a temporary trial period may be suggestive of later efficacy with SCS,
      it may not be the sole predictor of success. Alternatively, the arbitrary
      benchmark of 50% pain relief that is typically used to define the success of a
      temporary trial may be too stringent and unreliable.

PMID- 22150995
TI  - Perception of quality of care: comparison of the views of patients' with lung
      cancer and their family members.
AB  - AIMS AND OBJECTIVES: To explore potential differences within dyads of patients'
      with lung cancer and family members' judgment of different aspects of quality of
      care and relationships between quality of care and personal and health-related
      characteristics. BACKGROUND: High quality of care is important for acceptable
      quality of life in patients in palliative care. If patients are unable to
      participate in quality of care assessments or decision-making, family members
      might often act as proxies, despite the complicated nature of their own
      situation. DESIGN: Cross-sectional survey design. METHOD: A patient and family
      member version of the abbreviated questionnaire Quality from Patients'
      Perspective, with additional items about perceived health and opinions about
      care, was mailed to members of the Swedish lung cancer Patient Organisation.
      Wilcoxon's signed rank test was used to identify potential differences within 51
      patient-family member dyads' quality of care ratings. Relationships between
      Quality from Patients' Perspective dimensions and demographic and health-related
      variables were examined with Spearman's correlations. RESULTS: Patient-family
      member dyads had high levels of agreement in ratings of perceived reality of
      quality of care. Family members generally rated the subjective importance of
      individual items higher than did the patient in the dyad, with significant
      difference in the dimension 'socio-cultural approach'. Older patients were found
      to rate the physical-technical conditions higher than younger patients, in
      relation to perceived reality but not subjective importance. Women family members
      were found to rate the subjective importance of medical-technical competence,
      identity-oriented approach and socio-cultural approach significantly higher than
      men did. CONCLUSIONS: Patients with lung cancer and their family members agree in
      ratings of the perceived reality, but they differ more in ratings of the
      subjective importance of quality of care. When patients are unable to communicate
      their preferences, family members' opinions could be used as proxies concerning
      concrete aspects of quality of care. Concerning more subjective aspects, family
      members' ratings should be interpreted with precaution, as it could diverge from
      patients' own opinion. RELEVANCE TO CLINICAL PRACTICE: The perceptions of the
      importance of different aspects of quality of care were less related to health
      status than were judgments of quality of care received. This might suggest that
      the care patients received fulfilled neither the patients' nor family members'
      expectations, which is an important message to healthcare professionals and which
      would demand further exploration.

PMID- 22150996
TI  - Altemeier's procedure for rectal prolapse: analysis of long-term outcome in 60
      patients.
AB  - AIM: Altemeier's procedure (perineal rectosigmoidectomy) is the operation of
      choice for rectal prolapse in the elderly. The aims of this prospective
      observational study were to evaluate its long-term actuarial recurrence risk and
      the influence of the length of rectosigmoid resection and associated
      levatorplasty on recurrence rate and continence. METHOD: The perioperative and
      long-term data for all patients undergoing Altemeier's procedure since 1992 were
      analysed with regard to mortality, morbidity, continence, anorectal function and
      recurrence rate. RESULTS: Sixty patients [median age 77 years (35-98)] underwent
      rectosigmoid resection [median length of bowel 14 (6-60) cm] with associated
      levatorplasty in 21 (35%). Overall mortality and morbidity were 1.6 and 11.6%,
      respectively. Manometry showed increased anal sphincter basal pressure and
      maximal squeeze pressure. We observed a decrease in postoperative rectal
      compliance (P=0.002). Age, gender, prolapse duration before surgery,
      levatorplasty and length of resection had no statistically significant
      relationship with recurrence. Continence improved in 62% and was stable over a
      median follow-up of 48 (1-186) months. Continence was positively related to a
      short length of bowel resection, but not to decreased rectal compliance.
      Actuarial recurrence was 14% at 4 years. CONCLUSION: The long-term recurrence
      rate after the Altemeier procedure was low and not linked to resection length or
      to levatorplasty. Improvement in continence was stable over time.

PMID- 22150997
TI  - A dual approach employing MALDI-TOF MS and real-time PCR for fast species
      identification within the Enterobacter cloacae complex.
AB  - A real-time PCR procedure targeting the gene of the molecular cochaperon DnaJ
      (dnaJ) was developed for specific detection of strains belonging to the
      Enterobacter cloacae group. The inclusivity and exclusivity of the real-time PCR
      assay were assessed with seven reference strains of E. cloacae, 12 other
      Enterobacter species and 41 non-Enterobacter strains. Inclusivity as well as
      exclusivity of the duplex real-time PCR was 100%. In contrast, resolution of
      matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) was inadequate for delineation of Enterobacter asburiae,
      Enterobacter hormaechei, Enterobacter kobei and Enterobacter ludwigii from E.
      cloacae. Eleven of 56 (20%) clinical isolates of the E. cloacae group could not
      be clearly identified as a certain species using MALDI-TOF MS. In summary, the
      combination of MALDI-TOF MS with the E. cloacae-specific duplex real-time PCR is
      an appropriate method for identification of the six species of the E. cloacae
      complex.

PMID- 22150998
TI  - Principles for maintaining or increasing breast milk production.
AB  - Breastfeeding rates in many developed countries remain low, and maternal
      perception of insufficient milk production is a major contributing factor.
      Mothers with a perception of insufficient milk should be advised that normal
      breastfeeding frequencies, suckling times, and amounts are very variable. If
      objective assessment confirms insufficient milk production, mothers should ensure
      optimal milk removal frequency and thorough breast drainage. In addition,
      galactogogues can be prescribed. Understanding physiological principles
      underlying milk production will help clinicians reassure and assist mothers. 

PMID- 22150999
TI  - Performance analysis in sport: contributions from a joint analysis of athletes'
      experience and biomechanical indicators.
AB  - The purpose of this study was to test the usefulness of combining two types of
      analysis to investigate sports performance with the aim of optimizing it. These
      two types of analysis correspond to two levels of athletes' activity: (a) their
      experiences during performance and (b) the biomechanical characteristics of their
      movements. Rowing served as an illustration, and the activity of one female crew
      member was studied during a race. Three types of data were collected: (a)
      audiovisual data recorded during the race; (b) verbalization data obtained in
      interviews conducted afterward; and (c) biomechanical data. The courses of
      experience of the two rowers during the race were reconstructed on the basis of
      the audiovisual and verbalization data. This paper presents a detailed analysis
      of a single phenomenon of the race experienced by one of the rowers. According to
      the coaches, it reflected a dysfunction in crew coordination. The aim of this
      analysis was to identify the biomechanical characteristics of the rowers'
      movements that might explain it. The results showed that the phenomenon could be
      explained principally by an amplitude differential between the two rowers'
      strokes. On this basis, the coaches defined new training objectives to remedy the
      dysfunction in crew coordination. 

PMID- 22151000
TI  - Healthcare expenditures for males with haemophilia and employer-sponsored
      insurance in the United States, 2008.
AB  - Although hemophilia has a potentially high economic impact, published estimates
      of health care costs for Americans with hemophilia are sparse and non-specific as
      to the non-bleeding complications of the disease. The objective of this study is
      to estimate average annual health care expenditures for people with hemophilia
      covered by employer-sponsored insurance, stratified according to the influence of
      age, type of hemophilia [A (factor VIII deficiency) versus B (factor IX)],
      presence of neutralizing alloantibody inhibitors and exposure to blood-borne
      viral infections. Data from the MarketScan Commercial and Medicare Research
      Databases were used for the period 2002-2008 to identify cases of hemophilia and
      to estimate mean and median medical expenditures during 2008. A total of 1,164
      males with hemophilia were identified with continuous enrollment during 2008, 933
      with hemophilia A and 231 with hemophilia B. Mean health care expenditures were
      $155,136 [median $73,548]. Mean costs for 30 (3%) males with an inhibitor were 5
      times higher than for males without an inhibitor, approximately $697,000 [median
      $330,835] and $144,000 [median $73,321], respectively. Clotting factor
      concentrate accounted for 70%-82% of total costs. Average costs for 207 adults
      with HCV or HIV infection were 1.5 times higher than those for adults without
      infection. Hemophilia treatment is costly, particularly for individuals with
      neutralizing alloantibody inhibitors who require bypassing agents. Efforts to
      understand the cause of inhibitors are needed so that prevention strategies can
      be implemented and the excess costs resulting from this serious complication of
      hemophilia care can be avoided.

PMID- 22151001
TI  - MCR synthesis of praziquantel derivatives.
AB  - Schistosomiasis, a high volume neglected tropical disease affecting more than 200
      million people worldwide, can only be effectively treated by the
      tetrahydroisoquinoline drug praziquantel (PZQ). Herein, we describe an efficient
      approach to access PZQ derivatives by the Ugi 4-component reaction followed by
      the Pictet-Spengler reaction in a two-step, one-pot procedure. 30 novel PZQ
      derivatives are described based on the Ugi 4-component reaction and an X-ray
      structure of a novel derivative revealing different conformation compared with
      PZQ is discussed. Several analogues comparable in activity to the drug PZQ have
      been identified based on an in vitro Schistosoma mansoni worm viability assay.

PMID- 22151003
TI  - Combined effect of 25-OH vitamin D plasma levels and genetic vitamin D receptor
      (NR 1I1) variants on fibrosis progression rate in HCV patients.
AB  - BACKGROUND: Decreased vitamin D levels have been described in various forms of
      chronic liver disease and associated with advanced fibrosis. Whether this
      association is a cause or consequence of advanced fibrosis remains unclear to
      date. AIMS: To analyse combined effects of 25-OH vitamin D plasma levels and
      vitamin D receptor gene (VDR; NR1I1) polymorphisms on fibrosis progression rate
      in HCV patients. METHODS: 251 HCV patients underwent VDR genotyping (bat
      haplotype: BsmI rs1544410 C, ApaI rs7975232 A and TaqI rs731236 A). Plasma 25-OH
      vitamin D levels were quantified in a subgroup of 97 patients without advanced
      fibrosis. The VDR haplotype and genotypes as well as plasma 25-OH vitamin D
      levels were associated with fibrosis progression. RESULTS: The bAt[CCA]-haplotype
      was significantly associated with fibrosis progression >0.101 U/year (P = 0.007;
      OR = 2.02) and with cirrhosis (P = 0.022; OR = 1.84). Forty-five percent of
      bAt[CCA]-haplotype patients were rapid fibrosers, 21.1% were cirrhotic. Likewise,
      ApaI rs7975232 CC genotype was significantly associated with fibrosis progression
      and cirrhosis. Lower plasma 25-OH vitamin D levels were significantly associated
      with fibrosis progression >0.101 U/year in F0-2 patients (P = 0.013). Combined
      analysis of both variables revealed a highly significant additive effect on
      fibrosis progression with 45.5% rapid fibrosers for bAt[CCA]-haplotype and 25-OH
      vitamin D < 20 MUg/L compared with only 9.1% for the most favourable combination
      (P = 0.006). In multivariate analysis, the bAt-haplotype was an independent risk
      factor for fibrosis progression (P = 0.001; OR = 2.83). CONCLUSION: Low 25-OH
      vitamin D plasma levels and the unfavourable VDR bAt[CCA]-haplotype are
      associated with rapid fibrosis progression in chronic HCV patients. In
      combination, both variables exert significant additive effects on fibrosis
      progression.

PMID- 22151002
TI  - Uptake of radiolabeled GlcNAc into Saccharomyces cerevisiae via native hexose
      transporters and its in vivo incorporation into GPI precursors in cells
      expressing heterologous GlcNAc kinase.
AB  - Yeast glycan biosynthetic pathways are commonly studied through metabolic
      incorporation of an exogenous radiolabeled compound into a target glycan. In
      Saccharomyces cerevisiae glycosylphosphatidylinositol (GPI) biosynthesis, [(3)
      H]inositol has been widely used to identify intermediates that accumulate in
      conditional GPI synthesis mutants. However, this approach also labels non-GPI
      lipid species that overwhelm detection of early GPI intermediates during
      chromatography. In this study, we show that despite lacking the ability to
      metabolize N-acetylglucosamine (GlcNAc), S. cerevisiae is capable of importing
      low levels of extracellular GlcNAc via almost all members of the hexose
      transporter family. Furthermore, expression of a heterologous GlcNAc kinase gene
      permits efficient incorporation of exogenous [(14) C]GlcNAc into nascent GPI
      structures in vivo, dramatically lowering the background signal from non-GPI
      lipids. Utilizing this new method with several conditional GPI biosynthesis
      mutants, we observed and characterized novel accumulating lipids that were not
      previously visible using [(3) H]inositol labeling. Chemical and enzymatic
      treatments of these lipids indicated that each is a GPI intermediate likely
      having one to three mannoses and lacking ethanolamine phosphate (Etn-P) side
      branches. Our data support a model of yeast GPI synthesis that bifurcates after
      the addition of the first mannose and that includes a novel branch that produces
      GPI species lacking Etn-P side-branches.

PMID- 22151004
TI  - A case of mobile and massive calcifications in the left ventricle with unknown
      etiology.
AB  - We report a case of mobile and massive calcification in the left ventricle of
      unknown etiology. The pathophysiology and management of this unique condition is
      described.

PMID- 22151005
TI  - Glucocorticoid replacement therapy and fibrinolysis in patients with
      hypopituitarism.
AB  - BACKGROUND: Hypopituitarism is associated with increased cardiovascular
      mortality, and it has been suggested that unphysiological glucocorticoid
      replacement regimens might contribute to this risk. Traditional glucocorticoid
      replacement regimens have often led to excessive serum cortisol levels. The
      hypercortisolaemia of Cushing's syndrome is associated with an increased risk of
      thromboembolism. OBJECTIVE: To examine whether short-term higher-dose
      hydrocortisone replacement regimens adversely affect the fibrinolytic system.
      DESIGN: Crossover study comparing tailored low-dose (LD) glucocorticoid regimen
      (mean, 17.5 mg hydrocortisone daily), with a traditional high-dose (HD, 30-mg
      hydrocortisone daily) regimen for 2 weeks. PATIENTS: Ten patients with
      hypopituitarism and ACTH deficiency - median (range) age, 59 (41-75) years - and
      10 age- and sex-matched controls. Nine patients had growth hormone deficiency
      (five replaced), nine patients had TSH deficiency (nine replaced), eight had
      gonadotrophin deficiency (five replaced). During the study, other pituitary
      hormone replacement therapy remained unchanged. Patients with acromegaly and
      Cushing's syndrome were excluded. MEASUREMENTS: Hourly serum cortisol for 11 h,
      plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and
      fibrinogen levels after 2 weeks of treatment with both LD and HD regimens.
      RESULTS: No overall significant differences were found between the three groups
      using the Kruskal-Wallis test: PAI-1: [median (range)] HD, 25 (5-53) ng/ml; LD,
      21 (4-56) ng/ml; controls, 27 (8-51); P = 0.3; tPA: HD, 10 (5-15) ng/ml; LD, 10
      (4-13) ng/ml; controls 10 (3-13); P = 0.46; and fibrinogen: HD, 2.5 (1.8-3.5)
      g/l; LD, 3.0 (2.3-4.4) g/l; controls, 2.6 (1.6-3.2): P = 0.97 In addition, no
      significant differences between HD and LD using Wilcoxon's paired test; PAI-1 (P
      = 0.91), tPAag (P = 0.47) and fibrinogen (P = 0.09). CONCLUSIONS: An increased
      dose of hydrocortisone for 2 weeks creates excessive glucocorticoid exposure, but
      does not significantly affect fibrinolytic-coagulation parameters.

PMID- 22151006
TI  - Invasive micropapillary carcinoma of the mammary glands in a mare.

PMID- 22151007
TI  - The Huntington's Disease health-related Quality of Life questionnaire (HDQoL): a
      disease-specific measure of health-related quality of life.
AB  - Huntington's disease (HD) is a genetic neurodegenerative disorder characterized
      by motor, cognitive and psychiatric disturbances, and yet there is no disease
      specific patient-reported health-related quality of life outcome measure for
      patients. Our aim was to develop and validate such an instrument, i.e. the
      Huntington's Disease health-related Quality of Life questionnaire (HDQoL), to
      capture the true impact of living with this disease. Semi-structured interviews
      were conducted with the full spectrum of people living with HD, to form a pool of
      items, which were then examined in a larger sample prior to data-driven item
      reduction. We provide the statistical basis for the extraction of three different
      sets of scales from the HDQoL, and present validation and psychometric data on
      these scales using a sample of 152 participants living with HD. These new patient
      derived scales provide promising patient-reported outcome measures for HD.

PMID- 22151009
TI  - Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma and
      future treatments for the poor responders.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The
      most common problem associated with HCC is a high risk of intrahepatic recurrence
      despite radical treatment, and in many patients, this recurrence has fatal
      consequences. For patients with advanced-stage HCC according to the Barcelona
      Clinic Liver Cancer staging system, the multikinase inhibitor sorafenib is the
      current standard of care. In contrast, hepatic arterial infusion chemotherapy
      (HAIC) is the recommended treatment in Japan for patients with intermediate-stage
      or advanced-stage HCC. In this review, we describe the use of HAIC for advanced
      HCC. Furthermore, we demonstrate an alternative therapy for HCC, the iron
      chelator deferoxamine, and discuss future therapeutic possibilities.

PMID- 22151008
TI  - The BB0646 protein demonstrates lipase and haemolytic activity associated with
      Borrelia burgdorferi, the aetiological agent of Lyme disease.
AB  - The etiological agent of Lyme disease, Borrelia burgdorferi, is transmitted by
      ticks of the Ixodes genus and, if untreated, can cause significant morbidity in
      affected individuals. Recent reports have shown that polyunsaturated fatty acids
      in the B. burgdorferi cell envelope are potential targets for oxidative damage,
      which can be lethal. How B. burgdorferi responds to this assault is not known.
      Herein we report evidence that bb0646 codes for a lipase that is located within
      the bosR operon and that has specificity for both saturated and polyunsaturated
      fatty acids. Specifically, strains harbouring mutated copies of the lipase,
      either in the form of an insertionally inactivated construct or site-directed
      mutations within the active site, demonstrated attenuated lipolytic and
      haemolytic phenotypes when compared with the isogenic parent and trans
      complements. In vivo analysis showed that while the bb0646 mutant remains
      infectious, the spirochaetal load is significantly lower than both the isogenic
      parent and the complemented mutant strains. Taken together, these data
      demonstrate that BB0646 is a broad substrate specific lipase that contributes to
      lipolytic and haemolytic activity in vitro and is required for optimal B.
      burgdorferi infection.

PMID- 22151010
TI  - A bileaflet CarboMedics aortic valve prosthesis with a new unusual "linear"
      central regurgitant jet: a sign of subtle incomplete closure of one leaflet?

PMID- 22151011
TI  - Disparities in provision of transplant information affect access to kidney
      transplantation.
AB  - Recently Centers for Medicare and Medicaid Services (CMS) began asking providers
      on Form-2728 whether they informed patients about transplantation, and if not, to
      select a reason. The goals of this study were to describe national transplant
      education practices and analyze associations between practices and access to
      transplantation (ATT), based on United States Renal Data System (USRDS) data from
      2005 to 2007. Multinomial logistic regression was used to examine factors
      associated with not being informed about transplantation, and modified Poisson
      regression to examine associations between not being informed and ATT (all models
      adjusted for demographics/comorbidities). Of 236,079 incident end-stage renal
      disease (ESRD) patients, 30.1% were not informed at time of 2728 filing, for
      reasons reported by providers as follows: 42.1% unassessed, 30.4% medically
      unfit, 16.9% unsuitable due to age, 3.1% psychologically unfit and 1.5% declined
      counsel. Older, obese, uninsured, Medicaid-insured and patients at for-profit
      centers were more likely to be unassessed. Women were more likely to be reported
      as unsuitable due to age, medically unfit and declined, and African Americans as
      psychologically unfit. Uninformed patients had a 53% lower rate of ATT, a
      disparity persisting in the subgroup of uninformed patients who were unassessed.
      Disparities in ATT may be partially explained by disparities in provision of
      transplant information; dialysis centers should ensure this critical intervention
      is offered equitably.

PMID- 22151012
TI  - Prevalence, presentation, and endovascular management of hemodynamically or
      clinically significant arterio-portal fistulae in living and cadaveric donor
      liver transplant recipients.
AB  - PURPOSE: To compare the prevalence (cadaveric vs. living donor transplants),
      clinical features, and the effectiveness of endovascular management of
      significant arterio-portal fistulae (APF) in liver transplant recipients.
      METHODS: A retrospective audit of liver transplant recipients in two institutions
      was performed (1996-2009). Significant APF were included and were defined as
      symptomatic and/or hemodynamically significant (causing graft dysfunction and/or
      having abnormal Doppler findings in the portal vein). Patients with significant
      APF were evaluated for presenting symptoms, imaging features, size/branch order
      portal vein involvement, and effectiveness of the endovascular management (coil
      embolization). RESULTS: Four significant APF were found in 1992 (0.2%) liver
      transplants. Two were symptomatic and two were asymptomatic but were
      hemodynamically significant with liver function test abnormalities. All four APF
      were found in cadaveric donor graft recipients (0.23%, N = 4/1753) and none in
      239 living donor graft recipients. However, there was no statistical difference
      between cadaveric and living donor graft recipients (p = 1.0, odds ratio = 1.23).
      Coil embolization was technically and clinically successful in all 4 without
      complications and causing normalization of the abnormal Doppler findings.
      CONCLUSION: Significant APF are a rare diagnosis (0.2% of transplants). Coil
      embolization is a safe and effective treatment option for APF in transplants.

PMID- 22151013
TI  - Arterial stiffness as a cause of cognitive decline and dementia: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Although arterial stiffness has recently been confirmed as a
      predictor of cardiovascular disease, the association between arterial stiffness
      and cognitive decline is less clear. AIM: We performed a systematic review and
      meta-analysis to examine the evidence for large artery stiffness as a cause of
      cognitive decline and dementia. METHOD: Electronic databases were systematically
      searched until September 2011 for studies reporting on the longitudinal
      relationship between any validated measure of large artery stiffness and
      cognitive decline or dementia. Meta-analysis was performed on four studies
      investigating the association between aortic pulse wave velocity and a decline in
      Mini-Mental State Examination scores. RESULTS: Six relevant longitudinal studies
      were located, conducted over an average of 5 years follow up. Arterial stiffness
      was predictive of cognitive decline in five/six studies. In meta-analysis, higher
      aortic stiffness predicted lower Mini-Mental State Examination scores within the
      sample (beta=-0.03, 95% confidence interval (CI): -0.06 to 0.01, n= 3947),
      although studies were not all homogeneous, and statistical heterogeneity was
      present (I(2) = 71.9%, P= 0.01). Removal of one study with a relatively younger
      cohort and lower median aortic stiffness found higher aortic stiffness to
      significantly predict cognitive decline (beta=-0.04, 95% CI: -0.07 to -0.01, n=
      3687) without evidence of heterogeneity (I(2) = 9.5%, P= 0.33). There was little
      research investigating the effects of aortic stiffness on the development of
      dementia. CONCLUSION: Aortic stiffness was found to predict cognitive decline in
      both qualitative review and quantitative analysis.

PMID- 22151014
TI  - Sex differences in the association between sleep duration, diet and body mass
      index: a birth cohort study.
AB  - Sex differences in the effects of sleep duration on dietary intake and eating
      behaviours were examined prospectively in relation to overweight/obesity at ages
      6 and 7. Using data from a representative sample (QLSCD 1998-2010) of children
      born in the province of Quebec (Canada), 1106 children were followed to age 6 and
      1015 to 7years. Average nocturnal sleep duration was surveyed annually from 2.5
      6years, food-frequency and eating behaviour questionnaires were administered at
      age 6, and body weight and height were measured at 6 and 7years. Associations
      were examined longitudinally and mediation examined with adjustments for
      potential confounders. In boys and girls, shorter sleep duration patterns were
      associated significantly with less favourable dietary intakes at 6years: boys
      consumed vegetables and fruits less frequently and meats/alternatives more
      frequently than boys with longer sleep patterns; and girls consumed vegetables,
      fruits and milk products less frequently and soft-drinks more frequently than
      girls with longer sleep patterns. However, boys with shorter sleep patterns were
      also more likely to eat at irregular hours or to eat too much/fast at 6years.
      These behaviours, and not dietary intake, mediated an inverse association between
      sleep duration and overweight/obesity in boys. Sleep duration did not associate
      with any problem eating behaviours or overweight/obesity in girls. Shorter sleep
      in early childhood appears to associate with problematic eating behaviours in
      boys and diet quality in both sexes, regardless of an association with
      overweight/obesity. This is important for public health and should be considered
      in relation to other diet-related diseases.

PMID- 22151015
TI  - Late-onset achalasia after esophageal atresia repair.
AB  - The development of achalasia in a patient with a history of esophageal atresia
      (EA) is rare. Here, we report a patient who had undergone surgery for EA at birth
      and presented achalasia at 30 years of age. He was successfully treated with
      laparoscopic surgery.

PMID- 22151016
TI  - Patient-controlled Analgesia in Intrathecal Therapy for Chronic Pain: Safety and
      Effective Operation of the Model 8831 Personal Therapy Manager with a Pre
      implanted SynchroMed Infusion System.
AB  - The Model 8831 Personal Therapy Manager (PTM) offers a patient-controlled
      analgesia (PCA) option for the SynchroMed Infusion System (Medtronic Inc.,
      Minneapolis, MN). The safety and effective operation of the PTM activator was
      evaluated in 45 patients in five European centers receiving intrathecal drug
      infusion for the treatment of chronic pain via a SynchroMed pump. The total
      volume of drug delivered intrathecally over a four-week follow-up period was
      calculated. Adverse events were recorded and pain levels were measured via the
      Visual Analog pain Scale (VAS), Brief Pain Inventory, and SF-12 Quality of Life
      scores. Patient satisfaction with the device and its instruction manual was also
      assessed by questionnaire. The expected and calculated intrathecal drug volumes
      (and therefore drug doses) were the same, demonstrating that the device worked as
      intended. There were no device-related serious adverse events. Overall, 96% of
      patients were satisfied with the activator. Patients appreciated being able to
      control their pain and considered the device and its instructions easy to use.
      The PTM was shown to be safe and functioning properly in the intrathecal
      treatment of pain. The successful addition of a PCA function to the SynchroMed
      system may create a new standard in intrathecal pain therapy.

PMID- 22151017
TI  - A Prospective, Randomized Trial of Intrathecal Injection vs. Epidural Infusion in
      the Selection of Patients for Continuous Intrathecal Opioid Therapy.
AB  - The objective of this study was to compare the cost and safety of intrathecal
      injection (IN) vs. epidural infusion (CE) trial and to provide a preliminary
      assessment of the prognostic value of each in the selection of patients for long
      term continuous intrathecal opioid therapy (CIOT). Thirty-seven patients with
      chronic nonmalignant pain who were being considered for CIOT were randomized to
      morphine trial by IN or CE. Analgesic response and complications were monitored
      throughout trial. Sixty-seven percent of IN (12/18) and 79% (15/19) of CE
      subjects reported good pain relief (defined as >= 50% pain reduction) and were
      implanted with a permanent infusion system. Eighty-nine percent (24/27) of
      subjects provided six-month CIOT follow-up data. Cost of trial and health care
      utilization during six months of CIOT were compared between groups. Analgesic and
      functional response during CIOT was also compared between IN and CE groups. The
      cost of IN trial was significantly less than CE trial (p < 0.001). Complications
      were generally mild in both groups, although opioid-related side effects tended
      to be more common in the IN group. Successful pain relief after six months of
      CIOT was reported by 10 (60%) and 14 (64%) patients who underwent IN and CE
      trial, respectively (p = 0.32; Fisher's exact test). There was no difference
      between IN and CE groups in McGill Pain rating, quality of life (VAS), mood
      (Profile of Mood States), or function (Sickness Impact Profile) after six months
      of CIOT. We conclude that intrathecal injection is a safe procedure for use in
      selection of patients for CIOT and is less costly than epidural infusion.
      Differences in pain and functional response to long-term opioids among patients
      selected by either trial method are not large.

PMID- 22151018
TI  - C1-c2 sublaminar insertion of paddle leads for the management of chronic painful
      conditions of the upper extremity.
AB  - While spinal cord stimulation has commonly been carried out using percutaneous
      leads, these devices have limitations in cervical implants due to problems with
      positional stimulation and lead migration. Paddle leads, by virtue of their
      design, are more stable in their apposition to the neural elements; however, mid
      and lower cervical insertions have been associated with both acute and subacute
      spinal cord injuries. These complications are likely related to limitations in
      canal diameter, as paddle leads occupy a greater volume than percutaneous leads.
      At C1-C2, the space around the spinal cord is more generous, and thus allows
      greater room for insertion of leads. We report a series of patients treated with
      a technique for the implantation of a C1-C2 paddle electrode that capitalizes on
      this anatomy while still meeting the need for paresthetic overlap in patients
      with upper extremity pain syndromes. While the technique is not novel, it has not
      yet been popularized (1). This paper is presented to increase implanters'
      awareness of the method, its safety and utility. Twenty consecutive patients with
      neuropathic pain syndromes of the upper extremity were implanted using this
      technique. Surgical implantation of leads was done under a general anesthetic. An
      upper cervical incision was used, and after performing minimal laminotomies at C1
      and C2, the lead was passed rostro-caudally under direct visualization beneath
      the lamina. Paresthetic overlap of pain segments was achieved in all but one
      patient. Pre and postoperative VAS scores were compared to evaluate effectiveness
      of treatment. Eighteen of 20 patients reported a significant benefit from
      stimulation, with an average of 63 percent reduction in pain scores. The only
      complication was a malpositioned lead that required reoperation to adjust
      placement. No patient suffered neurologic sequelae as a result of this procedure.
      We have found C1-C2 sublaminar insertions of paddle leads to be a safe and
      effective way of treating neuropathic pain phenomenon involving the upper
      extremity. To further assess the relative benefit over percutaneous leads, a
      prospective trial would be required.

PMID- 22151019
TI  - A portable device for experimental treatment of neurogenic detrusor overactivity.
AB  - The objective of this study was to evaluate the effect of automatic event-driven
      electrical stimulation on the dorsal penile/clitoral nerve for management of
      neurogenic detrusor overactivity in spinal cord injured subjects. In order to
      reach the objectives it was necessary to design and realize a portable device for
      ambulatory urodynamic studies which was able to activate an electrical stimulator
      when the detrusor pressure exceeded a certain threshold. The developed device was
      repeatedly tested in a healthy subject and subsequently tested in a spinal cord
      injured subject. In testing the automatic event-driven system in the spinal cord
      injured subject, detrusor contractions were successfully inhibited until a
      certain bladder volume was reached and no incontinence episodes were observed
      prior to disabling the system. The preliminary results indicate that automatic
      event-driven electrical stimulation on the dorsal penile/clitoral nerve can
      inhibit involuntary detrusor contractions in spinal cord injured subjects and
      hereby restore continence and increase bladder capacity.

PMID- 22151020
TI  - Static analysis of nippers pinch.
AB  - The purpose of the study was to present a method for the assessment of finger
      joint torques in two-fingered precision grips. The static analysis of various
      grips is important for the analysis of the mechanics of a human hand and the
      functional evaluation of grasping. We have built a grip-measuring device
      assessing the endpoint forces of two-oppositional grips. Through the simultaneous
      use of an optical measuring system and the grip-measuring device, the finger
      positions and the grip force acting on the object were obtained. A recursive
      computational method was used within the proposed static model of the finger to
      calculate the finger joint torques. In the paper a three-dimensional static model
      of the grip is presented and the calculated finger joint torques are shown. The
      repeatability within subject is analyzed for the assessed grip force and finger
      joint torques. The estimated joint torques corresponds to the amount of load on
      the finger joints during the isometric muscle contraction in nippers pinch.

PMID- 22151021
TI  - Pattern dependence in the stimulation-induced type transformation of rabbit fast
      skeletal muscle.
AB  - Little is known of the events that initiate the adaptive response of skeletal
      muscle to a sustained change in use. This study was designed to distinguish
      between the role of the electrical activity pattern and that of the resulting
      contractile force in driving different aspects of the response. A better
      understanding of these issues would lead to improved clinical protocols for
      functional electrical stimulation. Rabbit limb muscles were stimulated
      continuously for 12 weeks either at 2.5 Hz or with an equivalent optimized
      pattern producing peak forces three-fold higher. The two patterns induced similar
      changes in shortening velocity, myosin isoforms, and fatigue resistance. They had
      markedly different effects on twitch dynamics and summation ("doublet effect").
      This pointed to differences in activation that were not, however, attributable to
      sarcoplasmic reticulum Ca(2+)  transport ATPase activity. The optimized pattern
      maintained muscle bulk more effectively. We conclude that changes in myosin
      isoform composition and fatigue resistance are driven by aggregate impulse
      activity. Changes in Ca(2+)  transport and muscle bulk show a distinct pattern
      dependence.

PMID- 22151023
TI  - Effects of rosuvastatin and atorvastatin on glycaemic control in Type 2 diabetes-
      -the CORALL study.
AB  - AIMS: To examine whether high-dose statin therapy in Dutch European patients with
      Type 2 diabetes and dyslipidaemia influenced variables of glycaemic control.
      METHODS: The CORALL study, which was a 24-week, open-label, randomized, parallel
      group, phase IIIb, multi-centre study, was designed to compare the cholesterol
      lowering effects of rosuvastatin compared with atorvastatin in patients with Type
      2 diabetes. Fasting plasma glucose levels and HbA(1c) levels were collected at
      baseline and at 6 and 18 weeks. RESULTS: Treatment with the highest dose of
      statins, i.e. atorvastatin 80 mg and rosuvastatin 40 mg at 18 weeks from
      baseline, was associated with increase in HbA(1c) levels; baseline 57 +/- 11
      mmol/l (7.4 +/- 1.0%) to 61 +/- 14 mmol/mol (7.7 +/- 1.3%) (range 5.0-11.9) for
      atorvastatin (P = 0.003) and from baseline 60 +/- 11 mmol/mol (7.6 +/- 1.0%) to
      63 +/- 13 mmol/mol (7.9 +/- 1.2%) (range 5.7-12.3) for rosuvastatin (P < 0.001).
      Mean fasting plasma glucose increased from baseline 8.7 +/- 2.4 mmol/l to 9.5 +/-
      3.0 mmol/l upon treatment with atorvastatin 20 mg (P = 0.002) and 9.0 +/- 3.0
      mmol/l after treatment with 80 mg (not significant compared with baseline). The
      mean fasting plasma glucose did not change after treatment with rosuvastatin (9.1
      +/- 2.7 mmol/l at baseline, 8.9 +/- 2.7 mmol/l with 10 mg, 9.4 +/- 2.9 mmol/l
      with 40 mg). CONCLUSIONS: Glycaemic control deteriorated in patients with
      diabetes following high-dose statin therapy. Future controlled studies are needed
      to verify these findings and, if confirmed, determine whether such changes
      represent a true decline in glycaemic control. Presently, it appears that, based
      on the overwhelming prospective trial data available, the preventive effect of
      statin therapy supersedes that of the slight increase in HbA(1c).

PMID- 22151024
TI  - Lipodystrophia centrifugalis abdominalis infantilis: report of four cases.
AB  - Lipodystrophia centrifugalis abdominalis infantilis (LCAI) is a rare
      lipodystrophic disorder mainly affecting Eastern Asian children. We report the
      clinicopathologic findings of four Taiwanese children with LCAI in which local
      induration or ecchymotic changes preceded the skin depressions on the groin or
      abdomen.

PMID- 22151025
TI  - Evaluation of lateral flow devices for identification of infected poultry by
      testing swab and feather specimens during H5N1 highly pathogenic avian influenza
      outbreaks in Vietnam.
AB  - BACKGROUND: Evaluation of two commercial lateral flow devices (LFDs) for avian
      influenza (AI) detection in H5N1 highly pathogenic AI infected poultry in
      Vietnam. OBJECTIVES: Determine sensitivity and specificity of the LFDs relative
      to a validated highly sensitive H5 RRT PCR. METHODS: Swabs (cloacal and tracheal)
      and feathers were collected from 46 chickens and 48 ducks (282 clinical
      specimens) and tested by both LFDs and H5 RRT PCR. A subset of 59 chicken and 34
      duck specimens was also tested by virus isolation (VI), the 'gold standard'.
      RESULTS: Twenty-six chickens and 15 ducks were shown to be infected by at least
      one RRT PCR positive clinical specimen per bird. Bird-level sensitivity for the
      Anigen LFD was 84.6% for chickens and 53.3% for ducks, and for the Quickvue LFD
      65.4% for chickens and 33.3% for ducks. Comparison of the three clinical
      specimens revealed that chicken feathers were the most sensitive with 84% and 56%
      sensitivities for Anigen and Quickvue respectively. All 21 RRT PCR positive swabs
      from ducks were negative by both LFDs. However, duck feather testing gave
      sensitivities of 53.3% and 33.3% for Anigen and Quickvue respectively.
      Specificity was 100% for both LFDs in all investigations. CONCLUSIONS: Although
      LFDs were less sensitive than AI RRT PCR and VI, high titre viral shedding in
      H5N1 highly pathogenic avian influenza (HPAI) infected and diseased chickens is
      sufficient for a proportion of birds to be identified as AI infected by LFDs.
      Feathers were the optimal specimen for LFD testing in such diseased HPAI
      scenarios, particularly for ducks where swab testing by LFDs failed to identify
      any infected birds. However, specimens should be forwarded to the laboratory for
      confirmation by more sensitive diagnostic techniques.

PMID- 22151026
TI  - Letter from the Editor-in-Chief.

PMID- 22151027
TI  - Editorial.

PMID- 22151028
TI  - Postural changes in spinal cord stimulation perceptual thresholds.
AB  - Introduction. Spinal cord stimulation voltage thresholds have been observed to
      change with body position, but previously have not been characterized in detail.
      Design. Prospective case series. Methods. We have obtained voltage measurements
      at the threshold of perception in three body postures for patients with
      percutaneous dorsal epidural leads. Results. In our sample of 42 patients, we
      observed a significant (p = 0.000) increase in voltage requirements when moving
      from supine to sitting or standing positions. This increase can be represented as
      a linear slope (1.25) across a range of baseline voltage amplitudes. Ninety-five
      percent of patients experienced an increase, primarily between 11 and 25%.
      Conclusions. These observations have implications for the design, implantation,
      and clinical application of spinal cord stimulators.

PMID- 22151029
TI  - Effects of posture on stimulation parameters in spinal cord stimulation.
AB  - Objective. To examine the importance of posture on the efficacy of spinal cord
      stimulation in a population of chronic pain patients previously implanted with a
      spinal cord stimulator. Materials and Methods. Electrode leads (Octrode 2098,
      ANS) were placed percutaneously into the epidural space under fluoroscopic
      control (BV29, Phillips, Inc.) at either the cervical or thoracic vertebral
      level. Stimulation parameters were measured at least 24 h after initial
      Implantation, and as long as 3 y. All patients were asked to look forward and
      remain still in one of three positions: lying, sitting, and standing. At each
      posture, electrical stimulation was applied to the spinal cord. The voltages and
      pulse widths necessary to produce threshold paresthesia, therapeutic stimulation,
      and uncomfortable sensations were recorded. A stimulus frequency of 100 Hz was
      used for all subjects. Results. As previously described by Barolat(1), we found
      the thresholds for stimulation to be highest in the thoracic level. We also
      measured the largest usage range to be at this level. However, we found that this
      range varied greatly between patients and between postures. In 20 patients the
      threshold for paresthesia was lowest when lying, while in three patients it was
      lowest when sitting. The mean range and SD of stimulation required to achieve
      paresthesia at all three posture levels was found to be 0.113 +/- 0.062 MUC for
      leads in the cervical region (N = 11) and 0.494 +/- 0.297 MUC for leads in the
      thoracic region (N = 19). Conclusions. To provide adequate stimulation at all
      postures, multiple stimulation settings (programs) would be required.

PMID- 22151030
TI  - Patient-interactive, microprocessor-controlled neurological stimulation system.
AB  - Objectives. Recent technical improvements in implanted stimulation devices, in
      particular the development of programmable, multicontact devices, have
      facilitated their clinical application in the management of pain. If the
      capabilities of these devices are to be used to full advantage, adjustment after
      implantation demands a major investment of time and effort. Ideally, adjustment
      should be based upon psychophysical data of high quality; this imposes additional
      demands. Materials and Methods. We have developed a computerized system, designed
      for direct patient interaction and for greater ease of operation than the
      standard external devices provided with these implants. It rapidly tests the
      available contact combinations and stimulus pulse parameters, at a rate
      substantially greater than that of a skilled human operator using the standard
      device. At the same time, it records detailed, graphical data and patient ratings
      at varying thresholds. We have redesigned the system based upon our experience
      with a prototype interfaced to the bus of an IBM-compatible PC, c. 1983. The new
      system communicates through the serial port to a freestanding, dedicated
      interface, whose microprocessor in turn controls standard, commercial
      radiofrequency transmitters. This frees the host computer from stimulus
      timekeeping, allowing simultaneous entry of pain drawings and stimulation
      drawings by the patient, analysis of incoming data, and generation of complex
      "multichannel" stimuli. Furthermore, upgrades to the host computer to expedite
      these tasks generally will require no other hardware or software modifications.
      Results and Conclusions. Our patient-interactive computerized system has proven
      to be safe and effective clinically in adjusting implanted spinal cord
      stimulators. It offers advantages of data standardization and quality control, as
      well as delivery of novel pulse sequences and protocols to assess the treatment
      of pain and neurological disorders by electrical stimulation devices.

PMID- 22151031
TI  - Intrathecal opioid conversions: the importance of lipophilicity.
AB  - An intrathecal opioid infusion using an implanted programmable pump is frequently
      used for controlling refractory pain. Morphine, which is the only opioid
      presently approved by the FDA for use in such pumps, occasionally fails to work
      or is not tolerated by the patient; therefore other opioids are considered for
      infusions. When switching from one drug to another, it is important to consider
      not only equianalgesic dose conversions, but also lipophilicity. We report on
      three cases that demonstrate the need to use only a fraction of the equianalgesic
      dose when shifting from lipophilic to nonlipophilic opioids in such infusions.

PMID- 22151032
TI  - Long-Term Intrathecal (IT) Administration of Opioid and Bupivacaine Relieved
      Intractable Pain in a Patient with Familial Amyloidosis Polyneuropathy: A Case
      Report(1).
AB  - Introduction. At the present time, there is no reliable method or drug for
      effective relief of the severe pain caused by the amyloldotic polyneuropathy
      (AP). Objective. To explore the possibility of relieving this type of pain by
      intrathecal (IT) infusion of opioid (morphine or buprenorphine), with or without
      bupivacaine. Patients, Materials and Methods. A 49-year-old male AP patient with
      Intractable pain in the low back, lower abdomen, and lower extremities. Opioids
      (up to 20 mg parenteral morphine-eq/day), and epidural injections of morphine (up
      to 36 mg/day) failed to provide long-term satisfactory pain relief. Therefore, an
      IT catheter was inserted via the L3-L4 interspace with its tip located at the L1
      L2 intervertebral disk. Results. Intermittent IT injections of morphine from 5 to
      30 mg per day, for 124 days, and continuous IT infusion of morphine (2-4 mg/ml),
      combined with bupivacaine (1.0-2.0 mg/ml), in daily rates from 2 to 12 ml (median
      = 9.5) for another 67 days, were associated with occurrence of seizures,
      suspected to be caused by the IT morphine. Therefore, the IT morphine was
      replaced with IT buprenorphine. Thereafter, the pain was treated with IT infusion
      of buprenorphine (0.06 mg/ml) and bupivacaine (1.25 mg/ml) in daily rates from 4
      to 13 ml (median = 5) for another 676 days, until the patient's death, for
      reasons unrelated to the IT treatment. He experienced satisfactory pain relief
      with daily doses of IT opioid from 4.5 to 39 mg morphine-eq (median = 19.6 mg)
      and IT bupivacaine from 0 to 20 (median = 12.5). The mean visual Analog Scores
      (VASmean), decreased from 7 to 0 (out of 10), the gait improved; and nocturnal
      sleep increased from 1 to 7-8 hours. Respiratory insufficiency (attributed to an
      an IT daily dose of ~ 5 mg morphine) and orthostatic hypotension, pareses, and
      urinary retention occurring at low doses of (12-18 mg/day) of IT bupivacaine were
      recorded. The patient had the IT treatment for 867 days, of which 777 days (>
      90%) were spent at home. Conclusion. Long-term IT administration of opioid and
      bupivacaine provided satisfactory long-term pain relief in a patient with
      refractory pain due to AP.

PMID- 22151033
TI  - Robotic resection compared with laparoscopic rectal resection for cancer:
      systematic review and meta-analysis of short-term outcome.
AB  - AIM: The study aimed to compare robotic rectal resection with laparoscopic rectal
      resection for cancer. Robotic surgery has been used successfully in many branches
      of surgery but there is little evidence in the literature on its use in rectal
      cancer. METHODS:   We performed a systematic review of the available literature
      in order to evaluate the feasibility, safety and effectiveness of robotic versus
      laparoscopic surgery for rectal cancer. We compared robotic and laparoscopic
      surgery with respect to twelve end-points including operative and recovery
      outcomes, early postoperative mortality and morbidity, and oncological
      parameters. A subgroup analysis of patients undergoing full-robotic or robot
      assisted rectal resection and robotic total mesorectal excision was carried out.
      All aspects of Cochrane Handbook for systematic reviews and Preferred Reporting
      Items for Systematic Reviews and Metanalysis (PRISMA) statement were followed to
      conduct this systematic review. Comprehensive electronic search strategies were
      developed using the following electronic databases: PubMed, EMBASE, OVID,
      Medline, Cochrane Database of Systematic Reviews, EBM reviews and CINAHL.
      Randomized and nonrandomized clinical trials comparing robotic and laparoscopic
      resection for rectal cancer were included. No language or publication status
      restrictions were imposed. A data-extraction sheet was developed based on the
      data extraction template of the Cochrane Group. The statistical analysis was
      performed using the odd ratio (OR) for categorical variables and the weighted
      mean difference (WMD) for continuous variables. RESULTS: Eight non randomized
      studies were identified that included 854 patients in total, 344 (40.2%) in the
      robotic group and 510 (59.7%) in the laparoscopic group. Meta-analysis suggested
      that the conversion rate to open surgery in the robotic group was significantly
      lower than that with laparoscopic surgery (OR = 0.26, 95% CI: 0.12-0.57, P =
      0.0007). There were no significant differences in operation time, length of
      hospital stay, time to resume regular diet, postoperative morbidity and
      mortality, and the oncological accuracy of resection. CONCLUSION: Robotic surgery
      for rectal cancer has a lower conversion rate and a similar operative time
      compared with laparoscopic surgery, with no difference in recovery, oncological
      and postoperative outcomes.

PMID- 22151034
TI  - Workplace aggression experienced by frontline staff in dementia care.
AB  - AIM: To describe the frequency of aggressive acts experienced by frontline staff
      working in two models of dementia care: Residential Alzheimer's Care Centers and
      Secured Dementia Units and to explore the associations between aggressive acts
      experienced by frontline staff and factors related to the work context and care
      providers. BACKGROUND: Aggression towards healthcare providers in residential
      long-term care settings is well documented. However, few studies have examined
      associations between aggressive behaviours towards care providers and
      organisational factors. DESIGN: A cross-sectional survey. METHOD: The survey
      included demographic items and questions about aggressive acts experienced by
      staff and contextual factors. Analyses included: (1) descriptive statistics, (2)
      tests of difference (i.e. Student's t-test, Mann-Whitney U-test, chi-squared test
      and anova), (3) bivariate associations (i.e. Pearson and Spearman rank order
      correlations) and (4) multivariate linear regression. RESULTS: Ninety-one health
      care aides and licensed practical nurses working in four nursing units using two
      models of dementia care participated (response rate 81%). The most frequently
      reported types of aggression were physical assault (50% of staff, n = 45) and
      emotional abuse (48% of staff, n = 44). Aggressive acts were significantly
      associated with working in Secured Dementia Units rather than Residential
      Alzheimer's Care Centers. CONCLUSIONS: Frontline staff working in Secured
      Dementia Units were exposed to higher frequencies of various types of aggressive
      acts mainly initiated by residents. Future research needs to explore modifiable
      workplace factors associated with aggressive acts in a larger sample across a
      variety of long-term care settings. RELEVANCE TO CLINICAL PRACTICE: To prevent
      staff perceived aggressive acts, leaders and managers in dementia care need to
      acknowledge the complex topic of workplace aggression and encourage an open
      discussion among frontline staff without assigning blame. Care provider
      strategies for dealing with aggressive behaviour have to be implemented in
      policies and clinical practice.

PMID- 22151035
TI  - In vitro activity of antibiotic combinations against multidrug-resistant strains
      of Acinetobacter baumannii and the effects of their antibiotic resistance
      determinants.
AB  - Various combinations of antibiotics are reported to show synergy in treating
      nosocomial infections with multidrug-resistant (MDR) Acinetobacter baumannii (A.
      baumannii). Here, we studied hospital-acquired outbreak strains of MDR A.
      baumannii to evaluate optimal combinations of antibiotics. One hundred and twenty
      one strains were grouped into one major and one minor clonal group based on
      repetitive PCR amplification. Twenty representative strains were tested for
      antibiotic synergy using Etest((r)). Five strains were further analyzed by
      analytical isoelectric focusing and PCR to identify beta-lactamase genes or other
      antibiotic resistance determinants. Our investigation showed that the outbreak
      strains of MDR A. baumannii belonged to two dominant clones. A combination of
      colistin and doxycycline showed the best result, being additive or synergistic
      against 70% of tested strains. Antibiotic additivity was observed more frequently
      than synergy. Strains possessing the same clonality did not necessarily
      demonstrate the same response to antibiotic combinations in vitro. We conclude
      that the effect of antibiotic combinations on our outbreak strains of MDR A.
      baumannii seemed strain-specific. The bacterial response to antibiotic
      combinations is probably a result of complex interactions between multiple
      concomitant antibiotic resistance determinants in each strain.

PMID- 22151037
TI  - What nurses need to know regarding nutritional and immunobiological properties of
      human milk.
AB  - In this article, we discuss the nutritional and immunobiological components of
      human milk that nurses need to know to offer optimal care and education to their
      patients and families. We describe the major macronutrients and micronutrients in
      human milk that are essential to the growth and development of the newborn
      infant, and we discuss the immunobiological components of human milk that
      supplement and boost the newborn's immune system. 

PMID- 22151038
TI  - Samuel J. Hassenbusch III, MD, PhD February 6, 1954-February 25, 2008  President,
      North American Neuromodulation Society, 2001-2002.

PMID- 22151036
TI  - Dissecting the role of glutathione biosynthesis in Plasmodium falciparum.
AB  - Glutathione (gamma-glutamylcysteinyl-glycine, GSH) has vital functions as thiol
      redox buffer and cofactor of antioxidant and detoxification enzymes. Plasmodium
      falciparum possesses a functional GSH biosynthesis pathway and contains mM
      concentrations of the tripeptide. It was impossible to delete in P. falciparum
      the genes encoding gamma-glutamylcysteine synthetase (gammaGCS) or glutathione
      synthetase (GS), the two enzymes synthesizing GSH, although both gene loci were
      not refractory to recombination. Our data show that the parasites cannot
      compensate for the loss of GSH biosynthesis via GSH uptake. This suggests an
      important if not essential function of GSH biosynthesis pathway for the
      parasites. Treatment with the irreversible inhibitor of gammaGCS L-buthionine
      sulfoximine (BSO) reduced intracellular GSH levels in P. falciparum and was
      lethal for their intra-erythrocytic development, corroborating the suggestion
      that GSH biosynthesis is important for parasite survival. Episomal expression of
      gammagcs in P. falciparum increased tolerance to BSO attributable to increased
      levels of gammaGCS. Concomitantly expression of glutathione reductase was reduced
      leading to an increased GSH efflux. Together these data indicate that GSH levels
      are tightly regulated by a functional GSH biosynthesis and the reduction of GSSG.

PMID- 22151039
TI  - Management of intrathecal catheter-tip inflammatory masses: an updated 2007
      consensus statement from an expert panel.
AB  - Background.  Expert panel of physicians and nonphysicians, all expert in
      intrathecal (IT) therapies, convened in the years 2000 and 2003 to make
      recommendations for the rational use of IT analgesics based on the preclinical
      and clinical literature known up to those times, presentations of the expert
      panel, discussions on current practice and standards, and the result of surveys
      of physicians using IT agents. An expert panel of physicians and convened in 2007
      to review previous recommendations and to form recommendations for the rational
      use of IT agents as they pertain to new scientific and clinical information
      regarding the etiology, prevention and treatment for IT granuloma. Method.  A
      review of preclinical and clinical literature from 2000 to 2006 was undertaken
      and disseminated to an expert panel of physicians. Focused discussions concerning
      the rational use of IT agents and its relationship to the etiology of, prevention
      of, and treatment of IT granuloma were held. Results.  This report presents here
      new knowledge of the etiology of catheter tip granuloma and guidelines for its
      prevention and treatment.

PMID- 22151041
TI  - Perceived success and failure of intrathecal infusion pump implantation in
      chronic pain patients.
AB  - Objectives.  Over the past few years, there has been an increased reliance on the
      intrathecal delivery of drugs for patients suffering from intractable pain. We
      sought to demonstrate the effectiveness of the intrathecal pain pump by examining
      self-reported pre- and postimplantation pain levels. Methods.  Eighty-four
      patients who had elected to implant a Medtronic SynchroMed 1 or 2 system in order
      to control their pain were asked to complete a survey. The survey consisted of
      pain ratings before implantation, pain ratings postimplantation, medications used
      before and after implantation, and patient satisfaction with the procedure.
      Results.  Perceived success rate for implantation is 68%, when measured by the
      ability to reduce reliance on oral medication. When measured by willingness to
      undergo the procedure again, the success rate is 86%. Conclusions.  Overall, the
      implantation of an intrathecal pain pump is an effective way for most people to
      manage their intractable pain and reduce reliance on oral medications.

PMID- 22151040
TI  - Future directions for intrathecal pain management: a review and update from the
      interdisciplinary polyanalgesic consensus conference 2007.
AB  - Background.  Expert panels of physicians and nonphysicians, all expert in
      intrathecal (IT) therapies, convened in the years 2000 and 2003 to make
      recommendations for the rational use of IT analgesics, based on the preclinical
      and clinical literature known up to those times, presentations of the expert
      panels, discussions on current practice and standards, and the result of surveys
      of physicians using IT agents. An expert panel of physicians and nonphysicians
      has convened in 2007 to update information known regarding IT therapies and to
      update information on new and novel opioid and nonopioid analgesic compounds that
      might show promise for IT use. Methods.  A review of preclinical and clinical
      published relevant studies from 2000 to 2006 was undertaken and disseminated to a
      convened expert panel of physicians and nonphysicians to discuss new and novel
      analgesic agents for IT use. Results.  The panelists identified several agents
      that were worthy of future studies for the clinical and rational use of IT agents
      that are presented in this article. Conclusions.  A list of nonopioid IT
      analgesics, including gabapentin, adenosine, octreotide, the chi-conopeptide,
      Xen2174, the conopeptide, neurotensis 1 agonist, CGX-1160, the omega-conotoxin,
      AM-336, and physostigmine, were identified as worthy of future research by the
      panelists.

PMID- 22151042
TI  - An Open-Label, Multicenter Study of the Safety and Efficacy of Intrathecal
      Ziconotide for Severe Chronic Pain When Delivered via an External Pump.
AB  - Objectives.  The study aims to assess the safety and efficacy of intrathecal (IT)
      ziconotide when delivered via an external infusion system. Materials and Methods.
      Patients with severe chronic pain were implanted with an external infusion
      system, and IT ziconotide was titrated over one to four weeks. Safety was
      evaluated via adverse event (AE) reports, and efficacy measures included the
      visual analog scale of pain intensity (VASPI), categorical pain relief scale
      (CPRS), and clinical global impression (CGI). Results.  Sixty-four of the 71
      patients (90.1%) experienced an AE during titration; five patients developed
      meningitis after completing at least two weeks of therapy. A significant (p <=
      0.005) median percentage improvement in VASPI scores was seen at week 1 and
      maintained through week 4 (range: 11.0-32.6%); 53.6% of patients reported good to
      excellent pain control on the CGI and 52.2% of patients reported moderate to
      complete pain relief on the CPRS. Conclusions.  The study results suggest that a
      short-term trial of IT ziconotide using an external infusion system may be
      sufficient to assess patient response. High rates of AEs were noted; however,
      ziconotide-related AEs were consistent with those reported in previous trials.

PMID- 22151043
TI  - A case report of subcutaneous peripheral nerve stimulation for the treatment of
      axial back pain associated with postlaminectomy syndrome.
AB  - Objective.  This article aims to present a case of the use of an alternative form
      of neuromodulation for the treatment of axial back pain associated with
      postlaminectomy syndrome. Materials and Methods.  An elderly patient with long
      standing axial back pain in the setting of a prior decompressive laminectomy
      presented for evaluation and treatment. After failing to obtain significant
      benefit from more conservative measures, a trial of peripheral nerve stimulation
      (PNS) was performed. Results.  The patient reported > 75% relief of his pain
      during the seven-day trial period, and accordingly a permanent PNS system was
      implanted. The permanent system consisted of four Medtronic Quad Plus leads, two
      on each side of midline oriented horizontally over the L4-5 paraspinous muscles.
      Our patient was ultimately weaned off of all narcotic medications and, at one
      year follow-up, continues to report > 90% reduction of pain.

PMID- 22151044
TI  - Spinal cord stimulation in conjunction with peripheral nerve field stimulation
      for the treatment of low back and leg pain: a case series.
AB  - Background.  The treatment of chronic low back and leg pain remains a difficult
      medical challenge, particularly for patients with postlaminectomy syndrome. While
      spinal cord stimulation (SCS) has been a significant addition to the available
      options, it is often inadequate in relieving both the back and leg pain
      components. We hypothesized that for some patients the combination of SCS with
      peripheral nerve field stimulation (PNFS) would be a safe, effective alternative
      that would be more effective than either modality alone. Objective.  Our
      objective was to demonstrate the efficacy of PNFS used in combination with SCS
      for the treatment of chronic pain syndromes involving the lower back and legs.
      Study Design.  Case series. Methods.  A total of 20 patients with chronic low
      back and leg pain syndromes who had failed conventional therapies underwent
      implantation of a combination of traditional SCS and PNFS. Leads were placed in
      the epidural space, as well as superficially in the subcutaneous tissues of the
      lower back, directly in the region of maximum pain. Patients initially underwent
      a trial of stimulation to assess response, and a permanent system was implanted
      if patients reported greater than 50% pain relief during the trial. For some
      patients, a combination was used at the time of the initial trial. In other
      cases, the decision to proceed with the combination was made later, either at the
      time of permanent implant, or later on, after SCS alone failed to adequately
      control pain. Results.  In each case, PNFS was used in combination with
      traditional SCS for patients with chronic lower back and lower extremity pain.
      While not all of these patients ultimately proceeded with the combination of SCS
      and PNFS to control their pain, the majority of patients found the combination
      better in controlling their overall pain than either modality alone. In addition,
      using a combined approach at the time of trial provided a noninvasive and
      effective method of comparing the efficacy of each method, allowing patients to
      identify the best form of neuromodulation for their particular pain. Conclusions.
      Due to the availability of 16 contact capacity generators, neurostimulation with
      multiple leads in various combinations-including both epidural and peripheral
      nerve field stimulation simultaneously-can be applied safely and effectively. The
      availability of this combined approach for a trial of stimulation prior to
      implant allows patients to compare SCS to PNFS and to indicate a preference for
      one over the other or for the combination. We conclude that PNFS may be used in
      combination with SCS as a safe and effective alternative treatment for patients
      with chronic low back and leg pain, and further suggest that the combined
      approach should be considered as a treatment option for this population.

PMID- 22151045
TI  - Effect of subthalamic nucleus stimulation on severe striatal hand deformity in
      Parkinson's disease: a case report.
AB  - Striatal hand is a deformity encountered in Parkinson's disease and other
      parkinsonisms. It is characterized by extension that occurs at all the
      interphalangeal joints, flexion at the metacarpophalangeal joints, and ulnar
      deviation. It can be differentiated from levodopa-induced dystonia and primary
      dystonia, since the deformity exists continuously even during sleep. We
      experienced a case of Parkinson's disease with severe striatal hand deformity
      which was successfully treated by deep brain stimulation of the subthalamic
      nucleus (STN-DBS). Although the precise mechanism remains unclear, rigidity is
      assumed to contribute to the limb deformities. Based on our experience, it seems
      possible therefore that the effect of STN-DBS on the hand deformity was a
      secondary effect on muscular rigidity. STN-DBS is assumed to represent a useful
      treatment option for striatal hand deformity.

PMID- 22151046
TI  - Transient Manic-like Episode Following Bilateral Deep Brain Stimulation of the
      Nucleus Accumbens and the Internal Capsule in a Patient With Tourette Syndrome.
AB  - Objective.  Deep brain stimulation (DBS) increasingly attracts attention as a
      potential treatment of mental disorders. Beside depression and obsessive
      compulsive disorders, DBS has already been shown to be beneficial for Tourette
      syndrome (TS). Clinical Presentation/Method.  The authors report on the outcome
      of a patient with treatment-resistant TS who underwent bilateral DBS of the
      nucleus accumbens and the internal capsule. Results.  Within the 10-month follow
      up, a substantial reduction of tics has been observed. Yet, as a side-effect of
      DBS, the patient developed a transient manic-like episode when primarily
      stimulated by the most proximally contact in the internal capsule. Conclusions. 
      This case supports the hypothesis that DBS of the nucleus accumbens and the
      internal capsule represents an effective therapeutic alternative for otherwise
      treatment-resistant TS. Yet, future controlled studies are needed to determine
      optimal stimulation parameters and to reduce negative side-effects such as
      transient hypomanic episodes.

PMID- 22151047
TI  - Stimulation parameters after vagus nerve stimulator replacement.
AB  - Objectives.  This study aims to assess tolerability and efficacy of stimulation
      parameters after vagus nerve stimulator (VNS) pulse generator replacement.
      Materials and Methods.  We carried out an observational, retrospective study,
      reviewing our experience with VNS generator replacements in 28 epilepsy patients.
      Results.  Seven patients had actual end of battery life (EOBL) (with symptoms),
      and 21 patients had asymptomatic projected EOBL. When we reprogrammed stimulation
      parameters postoperatively, 17 of the 28 patients could not tolerate the
      preoperative baseline current settings, even one year later. There were no
      differences in pre- vs. postoperative seizure rates between patients who did or
      did not return to baseline settings. Failure to return to baseline current was
      not related to previous VNS duration, same- vs. different-battery generator
      replacements, or antiepileptic medication changes. Conclusions.  After VNS
      generator replacement, patients' common inability to tolerate preoperative
      current settings does not lead to more seizures. A chronic modification of the
      vagus nerve system's sensitivity to stimulation changes may be hypothesized.

PMID- 22151048
TI  - Interaction of artificial and physiological activation of the gastrocnemius
      during gait.
AB  - Objectives.  The purpose of this research was to understand the effects of
      surface functional electrical stimulation (FES) of the tibial nerve on the
      activation of the gastrocnemius medialis of the stimulated side. Methods.  FES
      was carried out on six healthy subjects, initiated at three different times
      during gait: early, mid, and late stance. Each stimulation burst consisted of 15
      pulses, applied for 300 msec, at 50 Hz stimulation frequency. Mixed model
      statistical analysis was carried out on the median onset and offset times of the
      gastrocnemius medialis and the root mean square of the interpulse interval
      responses. Results.  Results indicate that the electromyography response to FES
      is dependent on the time of application. The most prominent effects found in the
      intervals between the stimulation pulses (interpulse intervals) were found when
      stimulation was applied early in the stance phase. This study revealed that the
      only statistically significant effect on burst timing was a delay in offset
      timing due to mid-timed stimulation. Conclusions.  We conclude that additional
      activation may have been compensated, at least in part, by blocking of the
      physiological activation during the stimulation burst.

PMID- 22151049
TI  - A pilot study to investigate the feasibility of electrical stimulation to assist
      gait in Parkinson's disease.
AB  - Objectives.  This study aims to investigate the effect of functional electrical
      stimulation (FES) on gait in people with Parkinson's disease. Materials and
      Methods.  Seven subjects with idiopathic Parkinson's disease received single
      channel electrical stimulation for eight weeks to the common peroneal nerve to
      improve heel strike and provide sensory stimulus during the swing phase of gait.
      Stride length, time, and number of steps to complete a 20-m walk and distance
      completed in 3 min were assessed. Episodes of freezing and incidence of falls
      were recorded. Statistical analysis of the walking test data was analyzed using
      the nonparametric Wilcoxon signed ranks test. Results.  An immediate improvement
      was demonstrated with FES on distance and average stride length during a 3-min
      walk during the treatment period but not on number of steps and walking speed
      during a 20-m walk. A training effect was observed for all parameters of gait
      measured over the eight-week treatment period, which was mostly maintained four
      weeks after treatment was stopped. Fewer falls and episodes of freezing occurred
      during the treatment period. The number of falls returned to pretreatment levels
      when treatment was stopped. Conclusions.  This study has shown that FES can
      improve some parameters of gait over an eight-week period of use with a carryover
      effect that is maintained without stimulation during that time and an immediate
      reduction in the frequency of falls. An immediate effect of FES was demonstrated
      over a 3-min walk but not over a 20-m walk. Improvements in gait largely
      persisted on reassessment four weeks after stopping use of FES although the
      frequency of falls returned to pretreatment levels. A larger study is required to
      support these findings, to understand the mechanisms of the effects of electrical
      stimulation on gait and to identify those most likely to benefit from it.

PMID- 22151050
TI  - A mechanistic insight into 3,4-methylenedioxymethamphetamine ("ecstasy")-mediated
      hepatotoxicity.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a popular drug of abuse
      among young people with stimulant and hallucinogenic properties. The drug is
      generally thought to be safe among consumers due to its low-mortality rates.
      However, MDMA-adverse effects can occur and the risks are not clearly associated
      to a specific pattern since the consumption quantity seems not to be correlated
      with the initiation and severity of the injury. MDMA-mediated adverse health
      effects have been widely studied and can be evoked by multiple factors such as
      hyperthermia, polydrug abuse (drug-drug interactions), the altered release of
      neurotransmitters, impairment of mitochondrial function and apoptosis, metabolism
      and immune responses. Another adverse effect often associated with MDMA is liver
      toxicity, yet the mechanism of MDMA-induced liver toxicity is not completely
      understood. A critical starting point appears to be the hepatic metabolism of
      MDMA by phase I and II enzymes, leading to reactive metabolites. Elucidating the
      mechanism of hepatic injury mediated by MDMA is of high toxicological and
      clinical relevance. In this review, an overview of the literature and the latest
      findings with respect to the mechanism of MDMA-mediated liver toxicity is
      described.

PMID- 22151051
TI  - Awareness regarding venous thromboembolism among internal medicine practitioners
      in Mexico: a national cross-sectional study.
AB  - BACKGROUND: Venous thromboembolism (VTE) affects millions of patients worldwide
      and is responsible for thousands of hospitalisations annually. AIMS: To evaluate
      the awareness regarding VTE among Mexican internists. METHODS: We designed a
      cross-sectional survey using a questionnaire applied to Mexican internists mainly
      during academic meetings. RESULTS: We collected 1220 questionnaires. VTE was
      considered a potential complication for medical inpatients by 85% of the
      respondents, whereas 69% and 63%, respectively, considered pulmonary embolism to
      be a complication of deep vein thrombosis (DVT) and a cause of death. Awareness
      of some VTE risk factors was adequate, and 85% of those physicians surveyed
      routinely observed patients for these risk factors, although only 58% performed
      global risk stratification. Only 12% of the respondents considered length of
      hospital stay as a risk factor, and 58% assumed that the risk decreases after
      hospital discharge; 64% and 49% responded that the risk is higher, and VTE risk
      factors are more frequent in surgical versus medical inpatients respectively. VTE
      diagnosis was reported as easy or very easy for 59% of the respondents, but only
      41% regarded phlebography as the gold standard for diagnosing DVT, although 85%
      of the respondents reported that d-dimer + Doppler ultrasound was an alternative.
      Pulmonary arteriography or helical computed tomography CT scan was the gold
      standard for diagnosing pulmonary embolism for 60% of the physicians, but 55%
      responded that electrocardiogram, arterial gasometry and chest X-ray are also
      useful. CONCLUSIONS: Awareness regarding VTE risk factors and the degree of
      diagnostic skills among Mexican internal medicine specialists are low.

PMID- 22151052
TI  - Arterial embolism caused by large mobile aortic thrombus in the absence of
      atherosclerosis, associated with iron deficiency anemia.

PMID- 22151054
TI  - Structural insights of the MLF1/14-3-3 interaction.
AB  - Myeloid leukaemia factor 1 (MLF1) binds to 14-3-3 adapter proteins by a sequence
      surrounding Ser34 with the functional consequences of this interaction largely
      unknown. We present here the high-resolution crystal structure of this binding
      motif [MLF1(29-42)pSer34] in complex with 14-3-3epsilon and analyse the
      interaction with isothermal titration calorimetry. Fragment-based ligand
      discovery employing crystals of the binary 14-3-3epsilon/MLF1(29-42)pSer34
      complex was used to identify a molecule that binds to the interface rim of the
      two proteins, potentially representing the starting point for the development of
      a small molecule that stabilizes the MLF1/14-3-3 protein-protein interaction.
      Such a compound might be used as a chemical biology tool to further analyse the
      14-3-3/MLF1 interaction without the use of genetic methods. Database Structural
      data are available in the Protein Data Bank under the accession number(s) 3UAL
      [14-3-3epsilon/MLF1(29-42)pSer34 complex] and 3UBW [14-3-3epsilon/MLF1(29
      42)pSer34/3-pyrrolidinol complex] Structured digital abstract *  14-3-3 epsilon
      and MLF1 bind by x-ray crystallography (View interaction) *  14-3-3 epsilon and
      MLF1 bind by isothermal titration calorimetry (View Interaction: 1, 2).

PMID- 22151055
TI  - Suffering and smiling: West African immigrant women's experience of intimate
      partner violence.
AB  - AIMS AND OBJECTIVES: This study reports the intimate partner violence experiences
      of West African women living in Australia. BACKGROUND: Increasing diversity in
      Australia's population presents new and complex challenges to nurses and other
      health care providers, particularly in relation to the health needs of immigrant
      women. DESIGN: A qualitative naturalistic inquiry design was used. METHOD: A
      convenience sample of 21 West African immigrant women in Australia who were 18
      years and over were engaged in face-to-face, in-depth interviews and asked to
      talk about their health experiences. The interviews were transcribed verbatim and
      analysed thematically. Intimate partner violence was revealed as a major theme in
      this analysis. RESULTS: Data revealed that eighteen of the women had experienced
      intimate partner violence. The women's accounts of intimate partner violence were
      dominated by two subthemes 'suffering in silence' and 'reluctance to seek help.'
      CONCLUSION: Findings revealed intimate partner violence as a significant issue
      for the newly migrated African women who participated in this study. RELEVANCE TO
      CLINICAL PRACTICE: Intimate partner violence is associated with significant
      adverse physical and psychological health outcomes. It is important that nurses
      understand the cultural barriers that can impede immigrant women's ability to
      seek out and receive appropriate support and intervention and provide
      opportunities for women to disclose experiences of intimate partner violence.

PMID- 22151056
TI  - Spinal cord stimulation and chronic critical limb ischemia.

PMID- 22151057
TI  - Quantitative aspects of the clinical performance of transverse tripolar spinal
      cord stimulation.
AB  - A multicenter study was initiated to evaluate the performance of the transverse
      tripolar system for spinal cord stimulation. Computer modeling had predicted
      steering of paresthesia with a dual channel stimulator to be the main benefit of
      the system. The quantitative analysis presented here includes the results of 484
      tests in 30 patients. For each test, paresthesia coverage as a function of
      voltage levels was stored in a computerized database, including a body map which
      enabled calculation of the degree of paresthesia coverage of separate body areas,
      as well as the overlap with the painful areas. The results show that with the
      transverse tripolar system steering of the paresthesia is possible, although
      optimal steering requires proper placement of the electrode with respect to the
      spinal cord. Therefore, with this steering ability as well as a larger
      therapeutic stimulation window as compared to conventional systems, we expect an
      increase of the long-term efficacy of spinal cord stimulation. Moreover, in view
      of the stimulation-induced paresthesia patterns, the system allows selective
      stimulation of the medial dorsal columns.

PMID- 22151058
TI  - A critical appraisal of the pain associated with iatrogenic adult spinal
      deformity, and treatment by spinal cord stimulation. A case report and review of
      the literature.
AB  - Objective. Over the past two decades, with the increasing use of spinal
      instrumentation to treat deformity, surgical restoration has become more
      frequent. A complication of surgical reconstruction for adult scoliosis, the
      iatrogenic flat back syndrome, has been described. Results of surgical
      realignment have been disappointing in terms of pain relief. The objective of
      this study is to examine a case of so-called flat back deformity and describe
      treatment via spinal cord stimulation. Materials and Methods. This is a case
      report of an individual who presented a spine center with the flat back deformity
      and pain. Results. Following exclusion of reversible compressive pathology, a 46
      year-old male with the iatrogenic flat back deformity and lumbosacral and thigh
      pain was treated with implantation of a thoracic spinal cord stimulator.
      Significant pain relief was obtained without resorting to additional major
      reconstructive surgery. Conclusions. Literature on the pain associated with flat
      back deformity is incomplete regarding description and characterization of pain.
      Given the unpredictability of spinal osteotomy to address this pain, a possible
      alternative treatment strategy is presented. This involves the use of selective
      pharmaceutical therapy and spinal cord stimulation. Based on the response of this
      patient to spinal cord stimulation, it is a possible that a component of this
      persistent pain is neuropathic, despite the fact that preoperative imaging
      studies failed to disclose a significant compressive lesion.

PMID- 22151059
TI  - Lumbar and Sacral Nerve Root Stimulation (NRS) in the Treatment of Chronic Pain:
      A Novel Anatomic Approach and Neuro Stimulation Technique.
AB  - Objective. The conventional technique used to stimulate the lumbar dermatomes is
      by stimulation of the dorsal columns of the spinal cord. Until recently,
      stimulation of nerve roots had not been successfully accomplished. We had
      performed selective nerve root cannulations for the placement of temporary
      catheters at cervical, thoracic, lumbar, and sacral levels in chronic pain
      patients using a caudad rather than craniad approach. We hypothesized that by
      stimulating the nerve roots we could improve paresthesia coverage in areas which
      cannot be covered effectively by spinal cord stimulation (SCS). To test this
      hypothesis, we have performed trials of nerve root stimulation (NRS) in patients
      who had failed SCS, or who were not candidates for SCS because their pain was
      otherwise inaccessible to stimulation. Methods. Five patients who had been
      unresponsive to conservative treatment, surgery, or SCS underwent 7-day trials
      with NRS. The diagnoses included: ilioinguinal neuralgia, discogenic low back
      pain, failed back syndrome, vulvodynia, and interstitial cystitis. We collected
      paresthesia maps, pain maps, pain visual analog scale (VAS) scores, and patient
      satisfaction ratings. Results. Paresthesia coverage was above 75% in all
      patients. VAS scores declined from a mean of 9 +/- 1.0 to 2.4 +/- 2.1 (p < 0.05,
      n= 5), all 5 patients requested permanent implantation, and 4 have been implanted
      so far. Conclusions. Lumbar and sacral NRS trials resulted in adequate
      paresthesia coverage and effective pain relief in all 5 patients. Further
      clinical trials to evaluate long-term success rates and safety are indicated.
      Detailed mapping studies are needed to evaluate the relationship between
      electrode placement and paresthesia patterns as well as the optimal stimulation
      parameters.

PMID- 22151060
TI  - The effects of spinal cord stimulation on quality of life in patients with
      therapeutically chronic refractory angina pectoris.
AB  - Objective. For patients with refractory angina pectoris, spinal cord stimulation
      (SCS) is a beneficial and safe adjuvant therapy. However, it has not yet been
      established whether SCS alters the quality of life (QoL) in these patients.
      Methods. In this study, 26 consecutive patients (age 61.3 +/- 7.0 years, 13
      females, angina duration 12.7 +/- 6.0 years) were recruited. Social, mental, and
      physical aspects of QoL were determined by Nottingham Health Profile (NHP I),
      depression scale (CES-D), scoring of angina pectoris attacks and short-acting
      nitroglycerine intake, pain score on the Visual Analog Scale (VAS), perceived
      health percentage, Satisfaction With Life scale (SWLS), and one-aspect Linear
      Analog Self Assessment scale (LASA). QoL outcomes at baseline were compared with
      reference values from healthy subjects. Within-group changes and magnitude of
      changes (effect size, ES) were assessed after 3 months and 1 year of SCS.
      Results. Compared to healthy subjects, the patients had significantly worse
      scores at baseline on NHP, SWLS, and LASA. After 3 months of SCS, NHP I aspect
      pain (ES = 1.39), AP-score (ES = 0.85), perceived health percentage (ES =- 0.80),
      NTG-use (ES = 1.08) and VAS-score (ES = 1.13) were all significantly improved (p
      < 0.05). After 3 months, moderate changes were observed; however, they were not
      statistically significant on the NHP-aspects "emotion" (ES = 0.57) and "sleep"
      (ES = 0.56). At the 1-year follow-up, significant and substantial improvements
      were found on NHP-I aspects: pain, energy, emotional reactions, social isolation,
      sleep, and physical mobility (p < 0.05) with changes that can be interpreted as
      large (ES > 0.80). Conclusion. QoL in patients with refractory angina pectoris is
      poor. Both pain and health aspects of QoL improved significantly after 3 months
      of SCS. Social, mental, and physical aspects of QoL were found improved after 1
      year of SCS.

PMID- 22151061
TI  - Spinal cord stimulation, conception, pregnancy, and labor: case study in a
      complex regional pain syndrome patient.
AB  - Introduction. Interventional modalities for pain treatment are reserved for
      patients failing multidisciplinary pain management, including psychological,
      physical, pharmacological, and anesthetic techniques. Objective. Medications for
      intractable pain may be unacceptable because the risk of teratogenic effects. The
      purpose of this study is to find out whether spinal cord stimulation may be safe
      during conception, pregnancy, and delivery. Materials and Methods. We report a 30
      year old, female, neonatal nurse who developed left hand burning pain, swelling,
      coldness, and weakness following a mild brachial plexus injury in a motor vehicle
      accident. The patient responded well to a combination of Neurontin, Trazadone,
      Ultram, and Vicodin. A year later, the patient married and wanted to become
      pregnant but was afraid of possible teratogenic effects of the medications.
      Therefore, she requested an interventional modality for control of her symptoms.
      We recommended spinal cord stimulation (SCS) based on our excellent experience
      with this modality in the management of complex regional pain syndromes (CRPS).
      However, we did inform the patient that no data had been published regarding the
      safety of this modality in pregnancy and labor. Results. Cervical SCS resulted in
      excellent pain control and discontinuation of the medications. Thirteen months
      later, she delivered a healthy five pound baby girl. Mother and baby were
      discharged home in two days. The SCS was not turned off at any time during the
      labor and delivery. Conclusion. SCS was safe for implantation in our case study
      of a pregnant woman. This may constitute a new indication for SCS in patients
      otherwise successfully managed with non-interventional modalities for pain
      control.

PMID- 22151062
TI  - Spinal cord stimulation for complex regional pain syndrome: a prospective study
      of 19 patients at two centers.
AB  - Objectives. Prospective studies using specific outcome measures for the treatment
      of complex regional pain syndromes (CRPS) using spinal cord stimulation are
      lacking in the literature. The current prospective study followed 19 patients
      with the objective of analyzing such patients using specific outcome measures
      including the McGill Pain Rating Index, the Sickness Impact Profile, Oswestry
      Disability, Beck Depression Inventory, and Visual Analog Scale Scores. Materials
      and Methods. Nineteen patients are reported as a subgroup enrolled at two centers
      participating in a multicenter study of efficacy/outcomes of spinal cord
      stimulation. These patients were specifically identified as having CRPS and
      followed as a separate group. Specific preimplant and postimplant tests to
      measure outcome were administered. Results. Statistically significant improvement
      in the Sickness Impact Profile physical and psychosocial subscales is documented.
      The McGill Pain Rating Index words chosen and sensory subscale also improved
      significantly as did Visual Analog Scale scores. The Beck Depression Inventory
      trended toward significant improvement. Conclusions. Patients with CRPS benefit
      significantly from the use of spinal cord stimulation, based on average follow-up
      of 7.9 months.

PMID- 22151063
TI  - Serum sclerostin levels were positively correlated with fat mass and bone mineral
      density in central south Chinese postmenopausal women.
AB  - OBJECTIVES: To investigate the relationship between serum sclerostin level, body
      composition, and bone mineral density (BMD) in central south Chinese
      postmenopausal women. METHODS: A cross-sectional study was conducted on 260
      healthy central southern Chinese postmenopausal women with vs without
      osteoporosis, aged 50-76 years old. Dual X-ray absorptiometry was used to measure
      the bone mineral content and BMD of the whole body, lumbar spine and left femur,
      and total body soft tissue composition. Serum sclerostin levels were measured by
      a quantitative sandwich enzyme-linked immunosorbent assay. RESULTS: Compared with
      women without osteoporosis, osteoporotic women had a significantly lower level of
      serum sclerostin (P = 0.001). Serum sclerostin levels were positively correlated
      with body weight, Ponderal index and fat mass. There was a positive correlation
      with the BMD of both the whole body and at various sites (P < 0.05), even after
      controlling for age, age at menopause, height and body weight. Multiple linear
      stepwise regression analysis showed that serum sclerostin level was the most
      significant determinant of both whole-body and lumbar spine BMD, compared with
      age, age at menopause, fat mass and lean mass. Age had similar impact as serum
      sclerostin on hip BMD. CONCLUSIONS: This study showed that in central south
      Chinese postmenopausal women, serum sclerostin is lower in women with
      osteoporosis than without. Serum sclerostin is positively correlated with fat
      mass and BMD for the whole body, lumbar spine and hip.

PMID- 22151064
TI  - Clinical sedation and bispectral index in burn children receiving gamma
      hydroxybutyrate.
AB  - BACKGROUND: Gamma-hydroxybutyrate (GHB) may be an interesting hypnotic agent in
      burn patients because of its good respiratory or hemodynamic tolerance. However,
      its clinical and electroencephalographic (EEG) sedative effects are not yet
      described in children. The aim of this prospective and randomized study was to
      assess clinical and EEG effects of increasing intravenous (IV) doses of GHB in
      burn children requiring sedation for burn wound cares. METHODS: Thirty six
      children hospitalized in a burn care unit were included and randomly assigned
      into three groups (G) according to the single IV dose of GHB they received before
      burn wound care: 10 mg . kg(-1) in G10, 25 mg . kg(-1) in G25, or 50 mg . kg(-1)
      in G50. All patients received oral premedication (morphine and hydroxyzine) 30
      min before GHB injection. Respiratory rate, heart rate, pulse oximetry, and
      bispectral index (BIS) were continuously monitored. Depth of sedation was
      clinically assessed using Observer's Assessment of Alertness and Sedation (OAAS)
      Score, every 2 min until recovery (i.e., OAAS = 4). RESULTS: Median age was 17.5
      [12-34] months. Whatever the dose, BIS decreased after IV GHB. Nadir value of BIS
      was significantly lower in G25 and G50 than in G10, as was for OAAS score. Nadir
      values were reached after same delays in G25 and G50. Duration of sedation was
      dose-dependent. CONCLUSION: Bispectral index decreased after GHB injection and
      was correlated with OAAS score. Deep sedation can be safely achieved with IV
      doses of 25 or 50 mg . kg(-1), but the last dose was associated with prolonged
      duration of clinical sedation.

PMID- 22151065
TI  - Living-donor liver transplantation for propionic acidemia.
AB  - Propionic acidemia is a rare autosomal recessive disorder affecting the
      catabolism of branched-chain amino acids because of a genetic defect in PCC.
      Despite the improvements in medical treatment with protein restriction,
      sufficient caloric intake, supplementation of l-carnitine, and metronidazole,
      patients with the severe form of propionic acidemia have life-threatening
      metabolic acidosis, hyperammonemia, and cardiomyopathy, which results in serious
      neurologic sequelae and sometimes death. This study retrospectively reviewed
      three children with neonatal-onset propionic acidemia who received LDLT. Between
      November 2005 and December 2010, 148 children underwent LDLT, with an overall
      patient survival of 90.5%, in our center. Three patients were indicated for
      transplantation because of propionic acidemia. All recipients achieved a
      resolution of metabolic derangement and better quality of life with protein
      restriction and medication, although urine methylcitrate and serum
      propionylcarnitine levels did not decrease markedly. LT can reduce the magnitude
      of progressive cardiac/neurologic disability as a result of poor metabolic
      control. Further evaluation is therefore required to determine the long-term
      suitability of this treatment modality.

PMID- 22151066
TI  - Access to primary dental care for patients with inherited bleeding disorders.
AB  - Patients with inherited bleeding disorders (IBD) can face difficulty in accessing
      primary dental care either due to disease-specific or patient-related barriers.
      This can lead to poor oral health and increase the need for more invasive dental
      treatment. This study aimed to highlight actual and perceived barriers that IBD
      patients from the East London area were experiencing. It also gives an overview
      of the experience history of the General Dental Practitioners (GDPs) treating
      these patients. Information was gathered via pre-designed surveys as part of a
      service development audit. A total of 105 anonymous patient surveys and 50 GDP
      surveys were completed between December 2010 and July 2011. The patient survey
      highlighted more patients to be affected by patient-related than disease-specific
      barriers to access dental care. The GDP survey identified that just under half of
      GDPs questioned were not confident in the dental management of patients with
      bleeding disorders. Identifying misconceptions and barriers to access primary
      dental care will enable further development of our shared-care approach between
      General Dental Services, Hospital or Community Dental Services and Haemophilia
      Centre, optimizing regular preventative advice and follow ups to prevent dental
      disease and invasive dental treatment requiring haemostatic treatment.

PMID- 22151068
TI  - Catheter tip granuloma associated with sacral region intrathecal drug
      administration.
AB  - Spinal cord compression from catheter tip granulomatous masses following
      intrathecal drug administration may produce devastating permanent neurologic
      deficits. Some authors have advocated intrathecal catheter placement below the
      conus medullaris to avoid the possibility of spinal cord involvement. Multiple
      cases of catheter tip granulomas in the thoracolumbar region have been reported.
      We present a unique case of a sacral region catheter tip inflammatory mass
      producing permanent neurologic deficits. A 71-year-old white male with a
      diagnosis of failed back surgery syndrome was referred to the senior author for
      evaluation. After more extensive conservative therapy, including spinal cord
      stimulation, failed to yield adequate pain relief, he was offered implantation of
      an intrathecal pump for opioid administration. Excellent pain relief was achieved
      in the postoperative period; however, three years after implantation, he
      presented with progressive saddle anesthesia and bowel/bladder incontinence.
      Magnetic resonance imaging demonstrated a space occupying lesion associated with
      the catheter tip. The patient underwent emergent second level complete sacral
      laminectomy with partial resection of an intradural extra-axial mass and removal
      of intrathecal catheter. At discharge, the patient had no restoration of
      neurologic function. Histologic examination of the mass confirmed a sterile
      inflammatory mass. It has been suggested that intrathecal catheters be placed
      below the conus medullaris to avoid the possibility of spinal cord involvement.
      We present an unusual case documenting devastating permanent neurologic deficits
      from a catheter tip granuloma in the sacral region.

PMID- 22151069
TI  - Psychophysical responses to experimentally induced heat and cold pain before,
      during, and after transcutaneous electrical nerve stimulation.
AB  - Objective.  The outcomes of different modes of TENS (transcutaneous electrical
      nerve stimulation) in relieving experimental heat and cold pain were studied.
      Materials and methods.  Three modes of stimulation, conventional, burst, and high
      rate frequency modulation (HRFM) including placebo, were trancutaneously applied
      to 20 right handed healthy volunteers (10 males and 10 females). Stimulation was
      carried out using two pad electrodes placed over the median nerve for 120 s in
      each case. Heat pain was induced to the right and left hands of each subject by
      means of a hot water bath and cold pain by means of frozen bottles. Pain scores
      based on Verbal Rating Scale (VRS) were recorded at 60 s intervals before,
      during, and after stimulation. Results.  All stimulation modes except placebo
      decreased VRS values down to statistically significant levels in each case (p <
      0.05). HRFM was the most effective mode of TENS causing a decrease of 53.1% to
      perception of heat pain during its application and 43.8% after HRFM in the right
      hand. In the left hand, these values were recorded as 46.8% and 40.3%,
      respectively. HRFM also decreased the perception of cold pain by 47.2% during
      stimulation and 44.5% after stimulation in the right hand. In the left hand, cold
      pain scores were reduced by 52.8% and 45.1%, respectively. There were no
      statistically significant sexual differences and no recorded statistically
      significant difference between the right or left sided stimulation. Conclusions. 
      All modes of stimulation statistically decreased both heat and cold pain when
      compared to placebo. HRFM was the most effective mode of TENS. It might be
      worthwhile to test the patterns of stimulation in chronic pain patients.

PMID- 22151070
TI  - Complications of epidural neuroplasty: a retrospective evaluation.
AB  - Percutaneous epidural neuroplasty (lysis of epidural adhesions, epidural
      application of hypertonic saline) is an interventional technique for the
      management of pain due to spinal disorders. Epidural neuroplasty is found to be
      effective in removing fibrous tissue occurring in the epidural space for various
      reasons, however, the procedure may be prone to serious complications. We present
      here our retrospectively collected complications and precautions of complications
      of epidural neuroplasty in 250 patients. Neuroplasty, as per the technique of
      Racz et al., was only considered in patients suffering from low back and cervical
      pain after conservative treatments had been tried and had failed. Possible known
      complications include bending of the tip of the introducer needle,
      shearing/tearing of the catheter, misplacement of the catheter, inadvertent
      blockage of the catheter or catheter tip, migration of the catheter, hypotension,
      respiratory depression, urinary and/or fecal incontinence, urinary hesitancy,
      sexual dysfunction, paresthesia, epidural abscess, and meningitis. We found the
      following complications in our series: the tips of the introducer needle were
      bent in 12 patients; catheter sheaths were torn during withdrawal through the
      needle in three patients; 39 patients had bleeding or aspiration of blood from
      the epidural space; eight patients had their catheters migrate into an epidural
      vein; one patient's catheter migrated into the prevertebral space during the
      procedure; there were dural punctures in 11 patients; there were catheter
      blockages in six patients during consecutive applications of neuroplasty;
      hypotension was seen during and after drug injections in 12 patients, there was
      hypotension in one patient; three patients had migration and penetration of their
      catheters into the dura after placement and in consecutive days; 25 patients
      experienced numbness in dermatomal areas of the upper and lower extremities
      depending the level of the procedure; and there were eight infections at the
      entry site of the catheter, three epidural abscesses, and two patients with
      meningitis. In order to prevent complications such as those seen, epidural
      neuroplasty procedures must be performed in well-equipped centers by experienced
      hands.

PMID- 22151071
TI  - Postoperative monitoring of the electrical properties of tissue and electrodes in
      deep brain stimulation.
AB  - The aim of this study was to investigate the causation of an insufficient
      clinical response to acute external stimulation after implantation of brain
      stimulating electrodes in patients with idiopathic Parkinson's disease (IPD).
      This study represents to our knowledge the first consecutive postoperative
      monitoring of the electrical properties of electrodes and tissue in this patient
      cohort. We hypothesized that changes in brain tissue resistance would be
      etiologic for this clinically observed phenomenon. Eight patients with IPD were
      monitored over a fixed time course (day 1-7). The voltage drop on the electrodes
      and in the tissue was measured. Our measurements indicate a significant
      inhomogeneity of the surrounding tissue and a marked interpatient difference of
      the electrode voltage drop. The changes of the voltage drop on the electrodes and
      the tissue were insignificant over the time course. We conclude that the decline
      of the clinical benefit is not due to an alteration of tissue resistivity. As an
      explanation, we postulate that the reactive formation/resolution of edema around
      the electrode has the same resistivity as the target and is therefore not
      detectable by our measurements or modulated by a still unknown mechanism.

PMID- 22151072
TI  - High Frequency Electrical Stimulation of the Stomach is More Effective than Low
      Frequency Pacing for the Treatment of Postoperative Functional Gastric Stasis in
      Humans.
AB  - The paper describes an original method of endoluminal electrical stimulation of
      the stomach developed by authors. The aim of the study was to compare two types
      of electrical stimulation: low frequency (LF) and high frequency (HF) in human
      patients. Twenty-three patients with postoperative gastroparesis (after abdominal
      surgery) were involved in the study and randomized into two groups. Group A
      consisted of 13 subjects treated by LF stimulation (mean age 52 +/- 11; five
      males, eight females) and group B of 10 patients scheduled for HF stimulation
      (mean age 61 +/- 8; six males, four females). A computer preprogrammable
      stimulator was used and the following parameters were evaluated: gastric
      retention every 12 h and symptoms score on the days 0, 1, 3, and 5. Gastric
      retention decreased in group A on consecutive days of pacing from 1,593 to 623,
      407, 315, 246, to 192 ml, and in group B from 1,980 to 570, 218, 80, 15, to 0 ml
      (p < 0.05). Symptoms score decreased on the consecutive days of pacing from 8.3
      to 3.8, 1.3, to 0.9 in the LF group and from 8.2 to 3.1, 1.0, to 0 in the HF
      group. We conclude that HF is more effective than LF in the treatment of
      postoperative gastroparetic human patients. No adverse effects of HF and LF were
      observed in this study.

PMID- 22151073
TI  - Fascicular selectivity in transverse stimulation with a nerve cuff electrode: a
      theoretical approach.
AB  - The performance of cathode-anode configurations in a cuff electrode to stimulate
      a single fascicle in a nerve trunk has been investigated theoretically. A three
      dimensional volume conductor model of a nerve trunk with four fascicles in a cuff
      electrode and a model of myelinated nerve fiber stimulation were used to
      calculate the recruitment of 15 m fibers in each fascicle. The effect of a
      monopole, a transverse bipole (anode opposite the cathode), and a narrow
      transverse tripole (guarded cathode) in selectively stimulating 15 m fibers in
      each fascicle has been quantified and presented as recruitment curves. It is
      predicted that selective fascicle stimulation is advanced most by stimulation
      with a bipole in a plane perpendicular to the axis of the nerve trunk. Monopoles
      and conventional longitudinal tripoles perform less well, as does a longitudinal
      tripole with an additional "steering" anode. Apart from transverse bipolar
      stimulation an additional anode may be used to maximally fit the area of
      excitation to the topography of the fascicle to be recruited. As compared to
      monopolar and longitudinal tripolar stimulation, the slope of the recruitment
      curves in transverse bipolar stimulation is reduced considerably, thus allowing
      improved fine tuning of nerve (and thus force) recruitment. Another advantage of
      this method is a minimal number of cable connections to the cuff electrode. The
      cost of the improved selectivity is an increased stimulation current.

PMID- 22151074
TI  - Letters to the editor.

PMID- 22151075
TI  - Letters to the editor.

PMID- 22151076
TI  - Letters to the editor.

PMID- 22151077
TI  - Letters to the editor.

PMID- 22151078
TI  - Results of live donor liver transplantation in patients with hepatitic C virus
      infection: the HCV 3 trial experience.
AB  - Chronic hepatitis C virus (HCV) is the most common disease indication for liver
      transplantation (LT). Outcomes are compromised by near universal recurrence of
      HCV. A prospective multi-center randomized study to evaluate immunosuppressive
      strategies in HCV+ transplant recipients provided the opportunity to assess
      impact of live donor (LD) LT. Two hundred and ninety-five patients undergoing LT
      for HCV (260 deceased donor [DD] recipients/35 LD recipients), randomized to
      three regimens, were followed for two yr for patient and graft survival and rate
      and severity of recurrent HCV. Biopsies were performed at baseline, 3, 12, and 24
      months. One- and two-yr patient survival for LD recipients was 88.1% and 81.1%
      vs. 90.5% and 84.6% for DD recipients (p = 0.5665). One- and two-yr graft
      survival for LD recipients was 82.9% and 76.2% vs. 87.9% and 81.7% for DD
      recipients (p = 0.3921). Recurrent HCV did not account for more deaths or graft
      losses in the LD recipients. In this prospective study, controlled for
      immunosuppression, use of LD organs did not increase the rate or severity of HCV
      recurrence. The more elective nature of LDLT affords an opportunity to manipulate
      donor and recipient factors that can impact upon outcomes.

PMID- 22151079
TI  - Sleep disturbance is associated with cardiovascular and metabolic disorders.
AB  - Existing research has demonstrated associations between sleep duration and
      obesity, diabetes, cardiovascular disease and mortality. Sleep disorders research
      has shown that sleep apnoea, insomnia and other sleep disorders confer risk for
      cardiometabolic disease, particularly in the presence of reduced sleep duration.
      The aim of the present study was to examine the associations between general
      sleep disturbance, operationalized as 'difficulty falling asleep, staying asleep,
      or sleeping too much' as measured in a large, nationally representative sample,
      and self-reported history of myocardial infarction, stroke, coronary artery
      disease, diabetes and obesity. Data from the Behavioral Risk Factor Surveillance
      System were analysed. Complete data were available for 138,201 individuals. A
      hierarchical logistic regression analysis examined associations before and after
      adjustment for demographic, socioeconomic, medical and psychological factors.
      After adjusting for demographic, socioeconomic and health risk factors, sleep
      duration was associated with obesity [odds ratio (OR)=1.18, P<0.0005), diabetes
      (OR=1.18, P<0.005), myocardial infarction (OR=1.36, P<0.0005), stroke (OR=1.22,
      P<0.05) and coronary artery disease (OR=1.59, P<0.0005). In fully adjusted models
      that included physical health, significant relationships remained for obesity
      (OR=1.14, P<0.0005), myocardial infarction (OR=1.23, P<0.005) and coronary artery
      disease (OR=1.43, P<0.0005). Sleep disturbance is a significant risk factor for
      obesity, diabetes, myocardial infarction, stroke and coronary artery disease, and
      effects for obesity, myocardial infarction and coronary artery disease are the
      most robust after adjustment. This study demonstrates that sleep disturbance is a
      novel risk factor that is potentially modifiable. Future research should
      determine whether sleep intervention could reduce the cardiometabolic
      consequences of sleep disturbance.

PMID- 22151080
TI  - Is abdominal obesity associated with the 2009 influenza A (H1N1) pandemic in
      Korean school-aged children?
AB  - OBJECTIVE: Given their medical vulnerabilities, we investigated the
      epidemiological factors related to H1N1 infection in school-aged children.
      METHODS: This study analyzed data collected on 7448 school-aged children in South
      Korea between 18 November and 8 December 2009. RESULTS: We found that H1N1
      infection was associated with body mass index (BMI), waist circumference (WC),
      the use of facemasks, contact history with H1N1-infected persons, and overseas
      travel history (P < 0.05). In addition, WC quartiles were significantly
      associated with H1N1 infection after adjusting for BMI and other confounding
      variables [OR (95% CI): 1.00, 1.10 (0.72-1.45), 1.13 (0.76-1.67), and 2.71 (1.74
      4.24), respectively). CONCLUSIONS: Abdominal obesity and the use of facemasks
      appear to be independently associated with H1N1 infection in school-aged
      children. We infer that providing education on wearing facemasks and specific
      planning for abdominally obese children and adolescents may be effective means of
      reducing the spread of the influenza pandemic in school-aged children.

PMID- 22151082
TI  - Prevention of neonatal group B streptococcus disease in the 21st century.
AB  - There have been significant reductions in early-onset neonatal group B
      streptococcus (GBS) disease following implementation of maternal intrapartum
      antibiotic prophylaxis (IAP) policies. Nevertheless, GBS remains a leading cause
      of neonatal sepsis in Australia and New Zealand resulting in considerable
      morbidity and mortality, particularly among preterm infants. In the United
      States, the universal screening-based approach for identifying women for IAP
      results in apparently lower rates of early-onset neonatal GBS infection than risk
      based assessment. In addition, IAP has altered the profile of newborn infants who
      develop early-onset disease. Many affected infants lack the typical intrapartum
      risk factors for GBS infection, are born to mothers with a negative GBS screen or
      represent missed opportunities for prevention. Clinicians should remain alert for
      signs of sepsis in any newborn infant. We provide an update of GBS preventative
      management strategies in the perinatal period taking into account recent United
      States, Australian and New Zealand guidelines.

PMID- 22151081
TI  - Stress induced Salmonella Typhimurium recrudescence in pigs coincides with
      cortisol induced increased intracellular proliferation in macrophages.
AB  - Salmonella Typhimurium infections in pigs often result in the development of
      carriers that intermittently excrete Salmonella in very low numbers. During
      periods of stress, for example transport to the slaughterhouse, recrudescence of
      Salmonella may occur, but the mechanism of this stress related recrudescence is
      poorly understood. Therefore, the aim of the present study was to determine the
      role of the stress hormone cortisol in Salmonella recrudescence by pigs. We
      showed that a 24 h feed withdrawal increases the intestinal Salmonella
      Typhimurium load in pigs, which is correlated with increased serum cortisol
      levels. A second in vivo trial demonstrated that stress related recrudescence of
      Salmonella Typhimurium in pigs can be induced by intramuscular injection of
      dexamethasone. Furthermore, we found that cortisol, but not epinephrine,
      norepinephrine and dopamine, promotes intracellular proliferation of Salmonella
      Typhimurium in primary porcine alveolar macrophages, but not in intestinal
      epithelial cells and a transformed cell line of porcine alveolar macrophages. A
      microarray based transcriptomic analysis revealed that cortisol did not directly
      affect the growth or the gene expression or Salmonella Typhimurium in a rich
      medium, which implies that the enhanced intracellular proliferation of the
      bacterium is probably caused by an indirect effect through the cell. These
      results highlight the role of cortisol in the recrudescence of Salmonella
      Typhimurium by pigs and they provide new evidence for the role of microbial
      endocrinology in host-pathogen interactions.

PMID- 22151083
TI  - Aortic valve replacement in patients with an anomalous left circumflex artery:
      technical considerations.
AB  - The abnormal origin of the left circumflex artery from the proximal right
      coronary artery (RCA) is considered a coronary artery anomaly. Most of the
      coronary artery anomalies are diagnosed incidentally by coronary artery
      angiography, and several considerations are needed to avoid fatal complications
      in patients undergoing aortic valve replacement (AVR). We report a case of AVR
      with anomalous origin of the left circumflex artery from a common ostium of the
      RCA, and discuss the use of a smaller prosthesis to avoid compression of the
      anomalous left circumflex artery.

PMID- 22151084
TI  - TNF-alpha genetic polymorphism -308G/A and antituberculosis drug-induced
      hepatitis.
AB  - BACKGROUND: While the mechanisms underlying the development of drug-induced liver
      injury are not clear, there is evidence to suggest that tumor necrosis factor
      alpha (TNF-alpha) plays an important role in drug- or drug metabolite-induced
      immune responses. We hypothesized that polymorphisms in the TNF-alpha gene are
      associated with anti-tuberculosis drug (ATD)-induced hepatitis. METHODS: Patients
      who suffered from ATD-induced hepatitis were enrolled in the study. ATD-induced
      hepatitis was defined as an increase in liver transaminase levels that were more
      than three times the upper limit of normal. ATD-tolerant patients were used as a
      control. Patients were treated with first line ATD therapies including isoniazid,
      rifampicin, ethambutol, and pyrazinamide. We compared the genotype frequencies of
      the TNF-alpha polymorphism -308G/A in 77 patients with ATD-induced hepatitis and
      229 ATD-tolerant patients. RESULTS: The frequency of carrying the variant allele
      (AG or AA) was significantly higher in patients with ATD-induced hepatitis
      compared with ATD-tolerant patients [26.0% vs. 15.3%, P = 0.034, OR (95% CI) =
      1.94 (1.04?3.64)] and the frequency of the A allele was significantly different
      between the two groups [0.143 vs. 0.079, P = 0.018, OR (95% CI) = 1.95
      (1.11?3.44)]. CONCLUSION: These results reveal that the TNF-alpha genetic
      polymorphism -308G/A is significantly associated with ATD-induced hepatitis. This
      genetic variant may be a risk factor for ATD-induced hepatitis in individuals
      from Korea.

PMID- 22151085
TI  - Innovations in the provision of human milk and breastfeeding for infants
      requiring intensive care.
AB  - Infant admission to the Neonatal Intensive Care Unit requires that the family
      receives the scientific rationale for the importance of providing human milk for
      their child. The initiation and maintenance of maternal milk supply must be a
      priority. Understanding variation in milk composition is crucial so that the
      infant receives the most appropriate milk throughout the hospital stay. For
      mothers who wish to breastfeed, a detailed and planned process is essential to
      ensure success. 

PMID- 22151086
TI  - A method for computing an inventory of metazoan mitochondrial gene order
      rearrangements.
AB  - BACKGROUND: Changes in the order of mitochondrial genes are a good source of
      information for phylogenetic investigations. Phylogenetic hypotheses are often
      supported by parsimonious mitochondrial gene order rearrangement scenarios. CREx
      is a heuristic for computing short pairwise rearrangement scenarios for metazoan
      mitochondrial gene orders. Different from other methods, CREx considers four
      types of rearrangement operations: inversions, transpositions, inverse
      transpositions, and tandem duplication random loss operations. RESULTS: An
      extensive analysis of the CREx reconstructions for artificial data has been
      presented and it is shown how the quality of the reconstructed rearrangement
      scenarios depends on the type of rearrangement model and additional parameter
      values. Moreover, a fast method is proposed to apply CREx to a large number of
      gene orders to find likely rearrangement scenarios and store them in a graph
      structure called RI-Graph. This method is applied to analyse all known metazoan
      mitochondrial gene orders. It is shown that the obtained RI-Graph contains many
      rearrangement scenarios that are described in the literature. CONCLUSIONS: The
      prospects and limitations of CREx have been analysed empirically and a comparison
      with the literature on gene order evolution highlights its benefits. The newly
      developed method to apply CREx to a large number of gene orders is successful in
      computing an RI-graph that contains many rearrangement scenarios for metazoan
      gene orders that have also been described in the literature. This shows that the
      new method is very helpful for a fast analysis of a large number of gene orders
      which is relevant due to the strongly increasing number of known gene orders.

PMID- 22151087
TI  - Multi-stage gene normalization for full-text articles with context-based species
      filtering for dynamic dictionary entry selection.
AB  - BACKGROUND: Gene normalization (GN) is the task of identifying the unique
      database IDs of genes and proteins in literature. The best-known public
      competition of GN systems is the GN task of the BioCreative challenge, which has
      been held four times since 2003. The last two BioCreatives, II.5 & III, had two
      significant differences from earlier tasks: firstly, they provided full-length
      articles in addition to abstracts; and secondly, they included multiple species
      without providing species ID information. Full papers introduce more complex
      targets for GN processing, while the inclusion of multiple species vastly
      increases the potential size of dictionaries needed for GN. BioCreative III GN
      uses Threshold Average Precision at a median of k errors per query (TAP-k), a new
      measure closely related to the well-known average precision, but also reflecting
      the reliability of the score provided by each GN system. RESULTS: To use full
      paper text, we employed a multi-stage GN algorithm and a ranking method which
      exploit information in different sections and parts of a paper. To handle the
      inclusion of multiple unknown species, we developed two context-based dynamic
      strategies to select dictionary entries related to the species that appear in the
      paper-section-wide and article-wide context. Our originally submitted BioCreative
      III system uses a static dictionary containing only the most common species
      entries. It already exceeds the BioCreative III average team performance by at
      least 24% in every evaluation. However, using our proposed dynamic dictionary
      strategies, we were able to further improve TAP-5, TAP-10, and TAP-20 by 16.47%,
      13.57% and 6.01%, respectively in the Gold 50 test set. Our best dynamic strategy
      outperforms the best BioCreative III systems in TAP-10 on the Silver 50 test set
      and in TAP-5 on the Silver 507 set. CONCLUSIONS: Our experimental results
      demonstrate the superiority of our proposed dynamic dictionary selection
      strategies over our original static strategy and most BioCreative III participant
      systems. Section-wide dynamic strategy is preferred because it achieves very
      similar TAP-k scores to article-wide dynamic strategy but it is more efficient.

PMID- 22151088
TI  - Ocular consequences of blunt trauma in two species of nocturnal raptors (Athene
      noctua and Otus scops).
AB  - OBJECTIVE:   To determine the type, prevalence, and prognosis of ocular and
      periocular lesions in free-living little owls (LO) and scops owls (SO), injured
      by blunt trauma. PROCEDURES:   Medical records from LO and SO with ocular or
      periocular lesions secondary to blunt trauma were reviewed. A complete ophthalmic
      examination was performed in all birds. Short protocol electroretinography (ERG)
      and ocular ultrasound were performed as dictated by the case. RESULTS:   During
      the study period, a total of 158 LO and 99 SO with blunt trauma were admitted.
      Among these, 43 LO (27.8%) and 27 SO (27.3%) had ocular or periocular lesions.
      Bilateral injuries (72.1% LO and 81.5% SO) were more common than unilateral.
      Common findings in both species were: corneal erosions/superficial ulcers,
      anterior and posterior uveitis, cataracts, hyphema, posterior synechia, vitreal
      hemorrhage, and retinal detachment. Electroretinography was performed in 32 LO
      and eight SO, which had posterior segment lesions or opacity of the transparent
      media. Normal to nonrecordable b-wave amplitudes were observed. Follow-up was
      available in 13 LO and 11 SO. Among these, nine LO (14 eyes) and 10 SO (17 eyes)
      had resolution of the clinical signs following medical treatment. CONCLUSIONS:  
      Ocular lesions are common in LO and SO injured by blunt trauma.
      Electroretinography is a valuable diagnostic tool to assess the severity of
      retinal dysfunction secondary to blunt trauma and to determine the response to
      medical treatment. A complete ophthalmic examination is a determining factor in
      the early management of trauma in these species.

PMID- 22151089
TI  - Specificity of motor components in the dual flagellar system of Shewanella
      putrefaciens CN-32.
AB  - Bacterial flagellar motors are intricate nanomachines in which the stator units
      and rotor component FliM may be dynamically exchanged during function. Similar to
      other bacterial species, the gammaproteobacterium Shewanella putrefaciens CN-32
      possesses a complete secondary flagellar system along with a corresponding stator
      unit. Expression of the secondary system occurs during planktonic growth in
      complex media and leads to the formation of a subpopulation with one or more
      additional flagella at random positions in addition to the primary polar system.
      We used physiological and phenotypic characterizations of defined mutants in
      concert with fluorescent microscopy on labelled components of the two different
      systems, the stator proteins PomB and MotB, the rotor components FliM(1) and
      FliM(2), and the auxiliary motor components MotX and MotY, to determine
      localization, function and dynamics of the proteins in the flagellar motors. The
      results demonstrate that the polar flagellum is driven by a Na(+)-dependent
      FliM(1)/PomAB/MotX/MotY flagellar motor while the secondary system is rotated by
      a H(+)-dependent FliM(2)/MotAB motor. The components were highly specific for
      their corresponding motor and are unlikely to be extensively swapped or shared
      between the two flagellar systems under planktonic conditions. The results have
      implications for both specificity and dynamics of flagellar motor components.

PMID- 22151090
TI  - Evidence-based medicine and neuromodulation.
AB  - Evidence-based medicine is gaining increasing penetrance in the United States.
      Neuromodulation providers need to know how to use this resource and how to get
      what we do appropriately evaluated and included in structured reviews and meta
      analyses. Randomized clinical trials are not the only form of evidence for
      patient care activities; other, equally valid strategies are available and should
      be used for interventions that may preclude blinding and randomization. Those who
      determine payment are going to use evidence-based medicine to make decisions that
      may not be in the best interests of our patients or our profession.

PMID- 22151091
TI  - Informed consent and decision-making capacity in neuromodulation: ethical
      considerations.
AB  - In neuromodulation treatment and research, the informed consent of the patient or
      research subject is considered to be a moral precondition. In order to be morally
      valid, the consent of the person should be informed and voluntarily given, and
      the person should have decision-making capacity. Decision-making capacity matters
      from a moral point of view because it enables the patient or research subject to
      make a well-considered decision about treatment or research participation.
      Decision-making capacity is an ideal and in the practice of neuromodulation may
      be compromised as a result of different circumstances. These may be internal or
      external. Internal are factors related to illness (ie, cognitive and emotional
      defects; feelings of desperation and hopelessness); external are factors related
      to the context (ie, shortcomings in patient education and communication). In this
      paper, it is argued that full decision-making capacity in the context of
      neuromodulation is an illusion. This does not imply that we should do away with
      the moral ideals of decision-making capacity and valid informed consent. It is
      part of the responsibility of clinicians involved in neuromodulation to be aware
      of and sensitive to the different threats to the decision-making capacity of
      patients suffering from neurological and neuropsychiatric disorders, and to
      assist patients in making decisions that are as well considered as possible in
      the given circumstances.

PMID- 22151092
TI  - Programmable infusion pump and catheter: evaluation using 3-tesla magnetic
      resonance imaging.
AB  - Objective.  This study assessed 3-Tesla magnetic resonance imaging (MRI) issues
      for a programmable infusion pump and associated catheters. Methods.  A
      programmable infusion pump and associated catheters (MedStream Programmable
      Infusion Pump, 40 mL; SureStream TI Coil-Reinforced Intraspinal Catheter;
      SureStream TI Connector; and SureStream Silicone Catheter; Codman and Shurtleff
      Inc., a Johnson & Johnson Company, Raynham, MA, USA) underwent evaluation for
      magnetic field interactions (deflection angle and torque), heating
      (transmit/receive body radiofrequency coil; whole-body averaged specific
      absorption rate, 3 W/kg for 15 min), functional changes (before and after MRI
      using eight different MRI conditions), and artifacts (T1-weighted spin-echo and
      gradient-echo pulse sequences) at 3-Tesla. Results.  The programmable infusion
      pump and associated catheters exhibited minor magnetic field interactions.
      Heating was not excessive (<= 1.9 degrees ), especially considering the
      experimental conditions used for this evaluation (ie, relatively high
      radiofrequency power/specific absorption rate level and use of a nonperfused
      phantom). The function of three out of six pumps was temporarily altered by
      exposures to 3-Tesla MRI conditions. Reset was achieved in each case. Artifacts
      were relatively large for the pump and minor for the catheter. Conclusions.  The
      programmable infusion pump and catheters will not pose increased risk to a
      patient examined using 3-Tesla MRI as long as specific safety guidelines are
      followed, which includes interrogation of the pump post-MRI to ensure proper
      settings. Artifacts for the programmable infusion pump may impact the diagnostic
      use of MRI if the area of interest is in the same area or near the device.

PMID- 22151093
TI  - Spinal cord stimulation has comparable efficacy in common pain etiologies.
AB  - Objectives.  The probability of success with spinal cord stimulation (SCS)
      depends largely on appropriate patient selection. Here, we have assessed the
      predictive value of pain etiology as it relates to pain relief with SCS as part
      of a prospective multicenter clinical trial. Methods.  Sixty-five subjects with
      chronic and intractable pain tested an epidural SCS system. Subjects reported
      pain ratings (visual analog scale) with stimulation off and stimulation on at
      scheduled follow-up visits for up to 18 months after activation of the system.
      Visual analog scale scores were averaged and stratified by dominant pain
      etiologies, comprising failed back surgery syndrome, complex regional pain
      syndrome, and a subgroup of subjects with miscellaneous other pain etiologies.
      Results.  More than 70% of subjects in each subgroup had successful outcomes
      during the temporary trial period and similar percentages of subjects from each
      etiology subgroup subsequently went on to permanent implantation. After permanent
      implantation, all subgroups reported more than 50% pain relief, on average, at
      each follow-up time point. No predictive value of pain etiology was observed.
      Conclusions.  Spinal cord stimulation is an effective therapy for neuropathic
      pain arising from a variety of causes. Failed back surgery syndrome, complex
      regional pain syndrome, and pain of other etiologies responded equally well to
      SCS.

PMID- 22151094
TI  - Automated vs. Manual Spinal Cord Stimulator Adjustment: A Sensitivity Analysis of
      Lifetime Cost Data From a Randomized Controlled Trial.
AB  - Objective.  In a randomized controlled trial comparing manual with automated
      computerized adjustment of spinal cord stimulators in patients with implanted
      power generators, automated adjustment conferred the following advantages: 1)
      more settings tested in a given time, 2) significantly greater pain/paresthesia
      overlap, 3) increased battery life, and 4) a $303,756 (95% confidence intervals =
      $116,503-491,009) reduction in lifetime per patient cost. The current study
      analyzes the sensitivity of this cost-savings to usage time/day, inflation,
      discount rate, and years of use. Methods.  We analyzed cost-sensitivity with a
      standard spreadsheet method and suitably adjusted standard equation. Results. 
      Regardless of hours of use/day, inflation, discount rate, or years of use, spinal
      cord stimulation remains significantly less expensive with automated rather than
      manual adjustment. This savings is attributable to increased battery life.
      Conclusion.  Sensitivity analyzes reveal that the significant cost-savings
      achieved with computerized, patient-directed adjustment of spinal cord
      stimulation in selected patients with chronic pain is robust across a
      representative range of parameters.

PMID- 22151095
TI  - c-Fos Expression After Chronic Electrical Stimulation of Sensorimotor Cortex in
      Rats.
AB  - Objectives.  Motor cortex stimulation has been used as a treatment for
      intractable pain. However, the mechanisms underlying its effects remain unclear.
      In this study, neuroplasticity induced by chronic sensorimotor cortex stimulation
      was investigated experimentally on the basis of c-Fos expression. Materials and
      Methods.  The experimental animals employed were adult male Wistar rats. A
      quadripolar stimulation electrode was positioned over the sensorimotor cortex. We
      examined the neural activation in response to chronic stimulation using c-Fos
      immunopositivity. Results.  The results are as follows: 1) c-Fos was
      significantly expressed immediately after the stimulation compared with that in
      the control; 2) c-Fos expression became extensive over the various regions with
      an increase in stimulation duration; and 3) after two months of stimulation, c
      Fos was expressed not only on the stimulation side, but also within the
      contralateral cerebral hemisphere. Conclusions.  Changes in c-Fos expression
      induced by long-term stimulation indicate the existence of a time-dependent
      neural plasticity.

PMID- 22151096
TI  - New animal model to mimic spastic cerebral palsy: the brain-damaged pig
      preparation.
AB  - Objective.  Classically, a decerebrated animal by mesencephalic lesioning is
      considered the paradigm for experimental study of spasticity that accompanies
      cerebral palsy, but, the model does not actually correspond with anatomical and
      pathologic realities. Therefore, a new and novel animal model is needed. Our
      objective was to create a more adapted animal model to be used in neuromodulation
      and functional electrical stimulation research. Materials and Methods.  Our new
      model in pigs closely simulates cortical and subcortical lesions produced by
      perinatal anoxic brain damage, which is present in spastic cerebral palsy and
      other spastic conditions. Our surgical lesions were produced by means of
      resecting the rolandic and perirolandic areas (cortical lesion) and aspiration
      and coagulation of white matter and deep gray nuclei. This model results in
      anatomic and pathologic configurations that are similar to human spastic cerebral
      palsy. We physiologically tested our model both in the pre- and postoperative
      situations. After experimental stimulation in nonoperated animals to establish
      mean latencies for preoperative bilateral cervical motor-evoked potentials and to
      confirm the absence of abnormally propagated electromyographic activity, another
      group of animals were retested using the same experimental variables before and
      after creation of the surgical lesioning in cortical and subcortical pyramidal
      areas. Results.  Normal latencies and no propagated electromyographic responses
      were found in sham animals. There were significant differences found in both
      latencies for motor-evoked potentials and electromyographic propagated responses
      when compared to pre- and postoperative values, which signaled abnormal
      physiology. Conclusions.  This animal model presents anatomic similarities to
      lesions currently present in cerebral palsy and related diseases. The model also
      shows electrophysiologic differences that signal chronic brain damage. Therefore,
      this method is useful in research when spastic syndromes produced by upper motor
      lesions need to be modeled.

PMID- 22151097
TI  - Lateral cord stimulation decreases spastic electromyographic spreading: responses
      in a brain-damaged pig preparation.
AB  - Objective.  The aim of our work was to investigate whether lateral stimulation of
      the spinal cord, lateral cord stimulation (LCS), results in inhibition of the
      spastic phenomena of upper motor lesions in an animal model. Methods.  This study
      was conducted using an animal model consisting of surgically brain damaged pigs
      subjected to unilateral cortical and subcortical brain lesions. A double
      laminectomy at cervical (C3-C4) and lumbar (L3-L6) was performed, and spastic
      thresholds of abnormal electromyographic responses, disseminated to adjacent
      segments, facilitated by spinal liberation, and produced by extradural electrical
      stimulation of the fourth lumbar root, were measured before and after cervical
      stimulation of the LCS. The variable studied was the minimal amount of current of
      LCS necessary to abolish electromyographic responses in the L7 myotome, away from
      the stimulated L4 nerve root. Results.  Experiments in 12 animals showed a
      significant increase of threshold after LCS, with a marked posteffect, signaling
      a less abnormal threshold. Conclusions.  This experiment demonstrated that LCS
      produces threshold increases to abolish abnormally propagated electromyographic
      evoked responses induced by the electrical stimulation of the fourth lumbar root
      in pigs with experimental cortical and subcortical brain lesions.

PMID- 22151098
TI  - Design and evaluation of a functional electrical stimulation system for hand
      sensorimotor augmentation.
AB  - The aim of this study was to perform a preliminary evaluation of a new method for
      therapeutic exercise of grasping in patients with upper limb disability. The new
      method combines active voluntary exercise augmented with electrical stimulation
      and controlled by using force feedback. The feedback has two functions: automatic
      control of the intensity of electrical stimulation by minimizing the tracking
      error, and biofeedback to the patient on the computer screen. The force feedback
      is realized by the use of a newly designed adjustable hand force measuring
      device, which comprises two force sensors. The therapy requires from patients to
      volitionally try to open and close the hand while tracking the target on the
      screen. The system was evaluated in a pilot study in five healthy and two chronic
      incomplete tetraplegic subjects. Results in healthy subjects were used for
      reference and for stimulation controller evaluation. The therapy in incomplete
      tetraplegic subjects of 45-min daily session delivered during four weeks. The
      results of pilot study show that augmentation of voluntary grip force control
      with presented system is possible.

PMID- 22151099
TI  - The effect of using variable frequency trains during functional electrical
      stimulation cycling.
AB  - Objectives.  This paper describes an experimental investigation of variable
      frequency stimulation patterns as a means of increasing torque production and,
      hence, performance in cycling induced by functional electrical stimulation.
      Materials and Methods.  Experiments were conducted on six able-bodied subjects
      stimulating both quadriceps during isokinetic trials. Constant-frequency trains
      (CFT) with 50-msec interpulse intervals and four catchlike-inducing trains (CIT)
      were tested. The CITs had an initial, brief, high-frequency burst of two pulses
      at the onset of or within a subtetanic low-frequency stimulation train. Each
      stimulation train consisted of the same number of pulses. The active torques
      produced by each train were compared. Parametric main effect ANOVA tests were
      performed on the active torque-time integral (TTI), on the active torque peaks
      and on the time needed to reach those peaks (T2P). Results.  The electrical
      stimulation of the quadriceps produced active torques with mean peak values in
      the range of 1.6-3.5 Nm and a standard error below 0.2 Nm. CITs produced a
      significant increase of TTI and torque peaks compared with CFTs in all the
      experimental conditions. In particular, during the postfatigue trials, the CITs
      with the doublet placed in the middle of the train produced TTIs and torque peaks
      about 61% and 28% larger than the CFT pattern, respectively. In addition, the
      CITs showed the lowest reduction of the performance between prefatigue and
      postfatigue conditions. Conclusions.  The use of CITs improves the functional
      electrical stimulation cycling performance compared with CFT stimulation. This
      application might have a relevant clinical importance for individuals with stroke
      where the residual sensation is still present and thus the maximization of the
      performance without an excessive increase of the stimulation intensity is
      advisable. Therefore, exercise intensity can be increased yielding a better
      muscle strength and endurance that may be beneficially for later gait training in
      individuals with stroke.

PMID- 22151100
TI  - Long-term outcomes of continuous intrathecal baclofen infusion for treatment of
      spasticity: a prospective multicenter follow-up study.
AB  - Long-term outcomes of 115 patients treated with continuous intrathecal baclofen
      infusion are reported. A prospective follow-up study was conducted in eight
      centers. Patients were followed up over a 12-month period. The follow-up scores
      on the three spasticity scales (Ashworth, spasm, and clonus scales) were
      significantly lower at every follow-up visit in comparison to the intake score,
      except for the clonus scale scores at 12 months. Improvements in health-related
      quality of life (EQ-5D) and functionality (SIP-68, functional independence
      measure) were small and nonsignificant. A significant reduction in severity of
      self-reported personal problems rating scale was observed. Sixty-six patients had
      no adverse events. Types of adverse events reported were wound complications
      (22%), catheter problems (36%), cerebrospinal fluid leakage (25%), and other
      complications (17%). Intrathecal baclofen reduces spasticity and severity of
      patient-reported problems but its effect on quality of life and functionality is
      less apparent. Improvements are desired in selection criteria, design of spinal
      catheters, and outcome scales.

PMID- 22151101
TI  - Barriers faced by migrants in accessing healthcare for viral hepatitis infection.
AB  - BACKGROUND: The morbidity and mortality of hepatitis B virus- and hepatitis C
      virus-related complications are disproportionately higher in the culturally and
      linguistically diverse population (CALD) when compared with Australian-born
      individuals. AIM: This project aims to elucidate the barriers faced by the CALD
      population in accessing viral hepatitis management. METHOD: CALD outpatients
      attending a viral hepatitis clinic in a tertiary teaching hospital were invited
      to participate in interviews. Questions pertained to: reason for screening for
      viral hepatitis, barriers to healthcare, perceived community view of viral
      hepatitis, main source of information of viral hepatitis and suggestions to
      engage members of CALD to seek healthcare. RESULTS: The total number of
      participants was 60. The two major countries of birth included China (40%) and
      Egypt (17%). In 40% of the cohort, viral hepatitis was identified through
      screening programmes. Importantly, 37% were diagnosed as a result of
      complications of hepatitis infection, presenting late in the stage of disease.
      Forty-five per cent of participants perceived language to be a chief barrier.
      twenty-two per cent reported cultural barriers to accessing healthcare. Of these,
      53% reported fear of discrimination/stigma. The lack of knowledge of available
      treatments/options was stated as a major obstacle in 40%. The two prevailing
      recommendations were greater education and awareness (85%) and changes in the
      health system itself (11%). CONCLUSION: Substantial hurdles identified by
      participants include cultural differences, language difficulties, cultural
      beliefs, stigma and misinformation. These data demonstrate the need for the
      greater dissemination of information in culturally and linguistically appropriate
      mediums to raise awareness about viral hepatitis, pathogenesis and available
      treatments.

PMID- 22151102
TI  - Identification and expression analysis of three novel splice variants of protein
      kinase A catalytic beta subunit gene in the mouse using combinatorial in silico
      and molecular biology approaches.
AB  - The murine, bovine and human protein kinase A catalytic beta (Cbeta) subunit
      genes encode several splice variants. Ten human Cbeta gene splice variants,
      namely Cbeta1, Cbeta2, Cbeta3, Cbeta3b, Cbeta3ab, Cbeta3abc, Cbeta4, Cbeta4b,
      Cbeta4ab and Cbeta4abc, have been reported. Four splice variants of the murine
      Cbeta gene are homologues of human Cbeta1, Cbeta2, Cbeta3 and Cbeta4 variants.
      Using a combinatorial approach comprising bioinformatics tools and molecular
      biology techniques, we have identified three novel alternatively spliced
      transcript variants of the mouse Cbeta gene designated Cbeta5, Cbeta6 and Cbeta7.
      These transcript variants differ in their first coding exon. New exons of Cbeta5
      and Cbeta6 variants can encode different N-terminals; however, the new exon of
      variant Cbeta7, when spliced with exon 2, encountered a stop codon in all three
      reading frames and thus cannot form a functional protein. The Cbeta6 variant
      showed an ubiquitous pattern of expression, whereas Cbeta5 was not expressed in
      muscle tissue on postnatal days (PN)3 and 15. Also, Cbeta7 was found to be
      expressed only in brain and muscle tissues at PN3 and was absent in all tissues
      examined at PN15 and PN60. The post-translational modification analysis showed
      characteristic signature sequence motifs in predicted proteins important for the
      functionality of the protein. The human homologues of variants reported in the
      present study have not yet been identified. The present study reports three novel
      splice variants that have not been identified using conventional approaches of
      alternative splice variant detection methods. Therefore, the approach used in the
      present study can be used to identify splice variants of genes in organisms.
      Database GenBank accession numbers: JN189786, JN189787 and JN189788.

PMID- 22151103
TI  - The effects of perceived stress and ways of coping in a sample of Portuguese
      health workers.
AB  - AIM: The goal of this study is to clarify the association between perceived
      stress in work and the types of coping strategies used by Portuguese nurses.
      BACKGROUND: The healthcare work environment as a source of overwork and stress
      has been implicated in today's nursing shortage. Staff nurses play a pivotal role
      in creating work environments, but little is known about the nature of Portuguese
      nurses' work. DESIGN: A descriptive correlational design and a cross-sectional
      approach were used for this study. METHOD: A total of 102 registered nurses, in
      three Portuguese hospitals, were selected. The Perceived Stress Scale and the
      Ways of Coping Questionnaire were used to measure job stress and coping
      strategies, respectively. RESULTS: High levels of stress were reported by 52.2%
      of respondents. The results showed that the main stressful factors for nurses are
      patient death and dying (32.8%), followed by emergency situations (22.8%) and low
      supportive relationships (18.0%). The most frequently used coping strategy was
      self-controlling, followed by planful problem-solving and seeking social support.
      Pearson's correlation tests indicated that the total score of the Perceived
      Stress Scale significantly negatively correlated with the subscales of the use of
      coping strategies of seeking social support, self-controlling, planful problem
      solving, distancing and escape-avoidance, indicating that those who were more
      distressed showed lower levels in mentioned coping subscales. CONCLUSION: Stress
      in nursing can be best reduced through the application of the control cycle
      approach and risk assessment/risk management techniques. Stress management of
      nurses may improve their productivity and quality of life. RELEVANCE TO CLINICAL
      PRACTICE: A change in leadership styles from the managerial level and
      reallocation of personnel may help reduce job stress. It is important for
      clinical practitioners to understand theoretical research concerning human stress
      responses, appraisal and coping to apply knowledge in practice when dealing with
      a client who has experienced a crisis.

PMID- 22151104
TI  - The importance of testing anti-IL-17 antibodies from different suppliers.

PMID- 22151105
TI  - A bibliometric search of citation classics in anesthesiology.
AB  - BACKGROUND: Articles cited counts are catalogued and help identify landmark
      papers. This study provides a citation classics of anesthesiology literature
      using the framework of subspecialties to provide a review of well-developed areas
      of research in anesthesiology. METHODS: A comprehensive list of the most-cited
      articles in anesthesia was compiled using a bibliometric database and general
      search terms such as "anesthesia" as well as subspecialty-specific search terms.
      Queries were reviewed for relevance to anesthesiology practice, categorized by
      subspecialty, and ranked according to their citation counts. RESULTS: The
      database resulted in 2519 articles published between 1945 and 2008. The specialty
      areas most represented were chronic pain medicine (11%), pharmacology (9%), and
      pain sciences (9%). CONCLUSIONS: This citations classic allows for advances in
      anesthesiology and its subspecialties to be highlighted as well to provide useful
      manuscripts to guide patient care, direct future research, and serve as sources
      for future academic pursuit.

PMID- 22151106
TI  - Comparison of size 2 i-gel supraglottic airway with LMA-ProSealTM and LMA
      ClassicTM in spontaneously breathing children undergoing elective surgery.
AB  - BACKGROUND: We compared size 2 i-gel((r)) (Intersurgical Inc.), a relatively new
      supraglottic airway device for use in spontaneously breathing anesthesized
      children with two different types of laryngeal mask airway-ProSealTM laryngeal
      mask airway (PLMA) and ClassicTM laryngeal mask airway (cLMA) for the ease of
      insertion, oropharyngeal sealing pressures (OSPs), and air leak. The hemodynamic
      effects on insertion of device and postoperative adverse effects were also noted.
      METHODS: A randomized prospective study was planned in 120 children aged 2-5
      years, weighing 10-20 kg, ASA physical status I-II scheduled for routine elective
      surgeries of <1-h duration. They were randomly divided in three groups (i-gel,
      PLMA, and cLMA) of 40 each, and a standard protocol for anesthesia was followed.
      RESULTS: The age, weight, height, and type of surgery were similar in all groups.
      Success rate for first attempt was 95% for the i-gel group and 90% for the two
      laryngeal mask airway groups. Insertion was found to be easy in the majority of
      cases in all groups, and there was no change in blood pressure, heart rate, or
      oxygen saturation on insertion. The OSP was 26 +/- 2.6, 23 +/- 1.2, and 22 +/-
      2.3 cm H(2)O for i-gel, PLMA, and cLMA, respectively. The difference between the
      i-gel and both laryngeal mask airway groups was statistically significant (P <
      0.01). There were no clinically important complications in the postoperative
      period. CONCLUSION: Pediatric size 2 i-gel is easy to insert and provides higher
      OSP compared with same size PLMA and cLMA in spontaneously breathing children
      undergoing elective surgery. It may be a safe alternative to laryngeal mask
      airways in day care surgeries.

PMID- 22151107
TI  - Institution of extracorporeal membrane oxygenation late after lung
      transplantation - a futile exercise?
AB  - The use of and indications for extracorporeal membrane oxygenation (ECMO) are
      expanding as its reliability improves with widely varying results reported. A
      retrospective review of 24 lung transplant recipients who required ECMO support
      postoperatively was performed with 13 patients requiring ECMO within the first 48
      h ("early" group) and 11 requiring ECMO after seven d postoperatively ("late"
      group). The majority of early ECMO group had primary graft failure patients and
      the late ECMO group comprised patients with infection or non-specific graft
      failure. There were significant differences in outcomes between groups, with
      10/13 in the early group and 4/11 in the late group successfully weaned from ECMO
      (p = 0.045). Six of the 13 patients in the early group and none of the late group
      survived to hospital discharge (p = 0.009). The late ECMO group had a much higher
      incidence of death owing to complications existing prior to institution of ECMO
      (essentially uncontrolled infection or organ failure). There were no differences
      in complications arising during ECMO between groups. Late institution of ECMO in
      lung transplant recipients for causes other than primary graft failure is
      associated with such poor survival that its use should be considered only in very
      select cases.

PMID- 22151108
TI  - Vitamin D, diabetic neuropathy and supplementation post-gestational diabetes.

PMID- 22151109
TI  - Intrathecal therapy for cancer and nonmalignant pain: patient selection and
      patient management.
AB  - Intrathecal drug delivery improves pain relief, reduces suffering, and enhances
      quality of life in the small proportion of patients who do not respond well to
      oral analgesics, including oral morphine. Although morphine is the "gold
      standard," and the only drug approved for intrathecal pain therapy in the United
      States, off-label use of alternative agents appears promising, particularly in
      patients with neuropathic pain. Careful patient selection and management are
      significant determinants of successful treatment outcomes. Patient selection
      criteria for cancer and nonmalignant pain are similar; however, a more
      comprehensive psychological and social assessment is required for patients with
      nonmalignant pain. In addition, all patients (those with cancer or nonmalignant
      pain) must exhibit a positive response to an epidural or intrathecal screening
      test. A multidisciplinary team approach, involving psychologists, nurses,
      physical therapists, social workers, and spiritual leaders should be used to
      manage patients. Current practices for patient selection and management,
      screening tests, and dosing guidelines for intrathecal drug delivery systems are
      discussed.

PMID- 22151110
TI  - Intrathecal opioid therapy for pain: efficacy and outcomes.
AB  - Although opioid therapy has been accepted for the treatment of patients with
      cancer pain, its use for nonmalignant pain is still regarded as controversial due
      to concerns about the development of tolerance and psychological dependence.
      However, recent studies indicate that there is a low incidence of addiction in
      patients who do not have a history of addictive disorders, and opioid use is
      increasing for long-term treatment in patients with nonmalignant pain. This paper
      reviews the results from recent studies that evaluated the efficacy of
      intrathecal opioid delivery using a number of outcome measures. These studies
      demonstrate that intrathecal opioid delivery produces short-term relief of
      specific symptoms and improves long-term outcomes such as patient functioning
      (measured by increases in activities of daily living [ADLs] and capacity to
      work), mood, treatment satisfaction, and quality of life, as well as decreases in
      oral opioid use. Furthermore, these studies showed there was no development of
      tolerance or addiction in patients who received long-term intrathecal opioid
      delivery.

PMID- 22151111
TI  - Cost effectiveness of intrathecal therapy for pain.
AB  - Successful management of chronic cancer and nonmalignant pain remains a challenge
      to clinicians, and cost effectiveness is an important consideration for clinical
      decision making. Although the oral route was previously considered the optimal
      method of chronic opioid administration, emerging evidence demonstrates a
      therapeutic advantage to intrathecal opioid delivery compared to alternative
      modalities. Intrathecal drug delivery uses an implantable drug infusion system to
      deliver very low doses of opioids and other analgesics directly into the
      intrathecal space. Although the initial costs of surgical implantation of an
      intrathecal pump appear to be substantial, maintenance costs of intrathecal drug
      delivery over time are significantly lower than other routes of administration,
      including oral and intravenous drug delivery. Cost analyses of alternate routes
      of opioid administration indicate that intrathecal delivery is the most cost
      effective route of opioid administration for patients who require long-term
      management of cancer (>= 3-6 months) or nonmalignant pain (>= 11-22 months).

PMID- 22151112
TI  - Alternative intrathecal agents for the treatment of pain.
AB  - There is a need to develop alternative agents for intrathecal pain therapy for
      patients who either cannot tolerate the side effects of or who no longer obtain
      sufficient analgesia with opioids. The experimental use of several compounds in
      intrathecal drug delivery is currently in progress, with the development of
      clonidine as the single most important advance in the improvement of pain
      treatment. Clonidine, an alpha(2) -adrenergic receptor agonist, appears to be
      safe and effective in the treatment of cancer and nonmalignant pain, with its
      effects most pronounced in patients whose pain consists of a neuropathic
      component. Other possible effective agents for intrathecal delivery include
      bupivacaine, octreotide, and SNX-111. The preclinical and clinical profiles for
      these promising new intrathecal pain medications are discussed.

PMID- 22151113
TI  - Drug adverse events and system complications of intrathecal opioid delivery for
      pain: origins, detection, manifestations, and management.
AB  - Intrathecal drug delivery is effective for the treatment of cancer and
      nonmalignant pain in patients who do not respond well to oral opioids, in
      patients who cannot tolerate the side effects associated with opioids, or in
      patients who show a large, permanent increase in dosage. Although intrathecal
      drug delivery is associated with pharmacological side effects and complications,
      its benefits far outweigh its risks. There are three main categories of potential
      adverse events associated with intrathecal drug delivery: pharmacologic side
      effects, surgical complications, and device-related complications. Prevention,
      early recognition, and prompt management of adverse events will optimize patient
      outcomes. Many adverse events either resolve on their own or can be managed with
      dosage or device adjustment. More serious complications may require surgical
      intervention or discontinuation of therapy. This paper will provide an overview
      of adverse events and complications, their origins, detection, manifestations,
      and management.

PMID- 22151114
TI  - Intrathecal baclofen therapy for spinal origin spasticity: spinal cord injury,
      spinal cord disease, and multiple sclerosis.
AB  - Spasticity can affect individuals with spinal injury, spinal disease, or multiple
      sclerosis. In most cases, spasticity is useful because it helps compensate for
      motor deficits. Oral medication is ineffective or produces intolerable side
      effects in ? 30% of patients with severe spasticity and surgeries can sometimes
      have effects inappropriate for patients requiring some degree of spasticity for
      function. Unsuccessful treatment of severe spasticity affects physical, social,
      and emotional functioning, as well as nursing care and overall cost of treatment.
      Intrathecal baclofen, a potent inhibitor of spinal synaptic reflexes, reduces
      both spasticity and spasms, thus leading to improvements in functioning and
      patient perception of quality of life, as well as ease of caretaking. Intrathecal
      baclofen can produce minimal side effects. The programmable pump allows precise
      dose titration that can be adjusted over a 24-h period for maximum effectiveness.
      Intrathecal baclofen generally remains effective for years without producing drug
      tolerance. Although complications are relatively uncommon, most involve
      mechanical compromise of the catheter. Cost analysis shows that there is an
      overall savings associated with intrathecal baclofen therapy, primarily due to a
      reduction in required hospitalizations and medical care for conditions resulting
      from spasticity. Intrathecal baclofen is a safe, efficacious, titratable,
      reversible, and cost-effective treatment for severe spinal origin spasticity,
      including spinal cord injury, spinal cord disease, and multiple sclerosis.

PMID- 22151115
TI  - Intrathecal baclofen therapy for spasticity of cerebral origin: cerebral palsy
      and brain injury.
AB  - Spasticity affects approximately 66% of individuals with cerebral palsy and 14%
      of the 100,000 individuals who, each year, experience brain injury in the US.
      This spasticity interferes with motor function and limits range of motion. It may
      cause pain and impede mobility, transfers, activities of daily living, sitting
      posture, and sleep. In addition, spasticity can contribute to the formation of
      pressure sores and joint contractures and make nursing or caregiving difficult.
      Several treatment options are available for intractable spasticity. For some
      diagnoses, oral medications are still the treatment of choice, while in other
      settings injection therapy may be more appropriate. If, however, they are
      ineffective or cause too many side effects, intrathecal baclofen therapy (ITB)
      may be a valuable alternative. ITB is effective, nondestructive, titratable, and
      reversible. In addition, it is associated with fewer CNS-related side effects
      than oral Lioresal (Novartis Pharma AG, Basel, Switzerland). Intrathecal baclofen
      therapy may improve range of motion, facilitate movement, reduce the patient's
      expenditure of energy, facilitate nursing, reduce the risk of developing
      contractures, and, in some cases, diminish pain resulting from spasticity and/or
      spasms. It also may improve speech, gait, upper extremity function, and
      activities of daily living, including communication, eating, dressing, hygiene,
      and other aspects of self-care. A recent study shows that treatment with
      intrathecal baclofen reduces the need for corrective orthopedic surgeries.
      Patient selection should be done in a multidisciplinary spasticity setting, where
      the expertise for different treatment modalities is available. Patients must be
      screened for response to the drug prior to implantation of the drug delivery
      pump. Maintenance doses for intrathecal baclofen range from 22 to 1400 MUg/day,
      with most patients adequately maintained on 90-703 MUg/day. Complications, while
      rare, are most often related to the drug delivery catheter. Intrathecal baclofen
      treatment may be cost effective, primarily due to a reduced need for
      hospitalizations and treatment of adverse events related to uncontrolled
      spasticity, and may improve quality of life. Intrathecal baclofen shows long-term
      efficacy in both higher and lower level patients with cerebral origin spasticity.

PMID- 22151116
TI  - Future trends in the development of local drug delivery systems: intraspinal,
      intracerebral, and intraparenchymal therapies.
AB  - Due to successful use of intrathecal drug delivery in the management of
      refractory pain and spasticity, new agents and indications are now being
      investigated. Preclinical studies of neurotrophic factors, molecules necessary
      for neuroneal survival and development, suggest that these agents may be
      beneficial for patients with neurologic disorders. Because neurotrophic factors
      do not cross the blood-brain barrier following systemic administration, local
      delivery routes, including intrathecal, intracerebroventrical, and
      intraparenchymal routes, are being studied; research is being conducted on
      intrathecal delivery for amyotrophic lateral sclerosis (ALS),
      intracerebroventricular delivery for Parkinson's disease and Alzheimer's disease,
      and intrahippocampal delivery for seizure disorders. Treatment of other
      neurologic disorders, such as brain tumors and HIV-related viral infections, also
      may be optimized by methods of local drug delivery, including intratumoral and
      intraparenchymal administration of potentially effective agents. Intraspinal,
      intratumoral, and intraparenchymal routes of administration are speculated to
      become critical components of treatment for a variety of neurological
      indications.

PMID- 22151117
TI  - The HOPE fixation technique--a promising alternative to common prostate cancer
      biobanking approaches.
AB  - BACKGROUND: The availability of well-annotated prostate tissue samples through
      biobanks is key for research. Whereas fresh-frozen tissue is well suited for a
      broad spectrum of molecular analyses, its storage and handling is complex and
      cost-intensive. Formalin-fixed paraffin-embedded specimens (FFPE) are easy to
      handle and economic to store, but their applicability for molecular methods is
      restricted. The recently introduced Hepes-glutamic acid-buffer mediated Organic
      solvent Protection Effect (HOPE) is a promising alternative, which might have the
      potential to unite the benefits of FFPE and fresh-frozen specimen. Aim of the
      study was to compare HOPE-fixed, FFPE and fresh-frozen bio-specimens for their
      accessibility for diagnostic and research purposes. METHODS: 10 prostate cancer
      samples were each preserved with HOPE, formalin, and liquid nitrogen and studied
      with in-situ and molecular methods. Samples were H&E stained, and assessed by
      immunohistochemistry (i.e. PSA, GOLPH2, p63) and FISH (i.e. ERG rearrangement).
      We assessed DNA integrity by PCR, using control genes ranging from 100 to 600 bp
      amplicon size. RNA integrity was assessed through qRT-PCR on three housekeeping
      genes (TBP, GAPDH, beta-actin). Protein expression was analysed by performing
      western blot analysis using GOLPH2 and PSA antibodies. RESULTS: Of the HOPE
      samples, morphologic quality of H&E sections, immunohistochemical staining, and
      the FISH assay was at least equal to FFPE tissue, and significantly better than
      the fresh-frozen specimens. DNA, RNA, and protein analysis of HOPE samples
      provided similar results as compared to fresh-frozen specimens. As expected, FFPE
      samples were inferior for most of the molecular analyses. CONCLUSIONS: This is
      the first study, comparatively assessing the suitability of these fixation
      methods for diagnostic and research utilization. Overall, HOPE-fixed bio
      specimens combine the benefits of FFPE- and fresh-frozen samples. Results of this
      study have the potential to expand on contemporary prostate tissue biobanking
      approaches and can serve as a model for other organs and tumors.

PMID- 22151118
TI  - Melatonin interferes in the desmoplastic reaction in breast cancer by regulating
      cytokine production.
AB  - Melatonin exerts oncostatic effects on breast cancer by interfering with the
      estrogen signaling pathways. Melatonin inhibits aromatase enzyme in breast cancer
      cells and fibroblasts. In addition, melatonin stimulates the adipogenic
      differentiation of fibroblasts. Our objective was to study whether melatonin
      interferes in the desmoplastic reaction by regulating some factors secreted by
      malignant cells, tumor necrosis factor (TNF)-alpha, interleukin (IL)-11, and
      interleukin (IL)-6. To accomplish this, we co-cultured 3T3-L1 cells with MCF-7
      cells. The addition of breast cancer cells to the co-cultures inhibited the
      differentiation of 3T3-L1 preadipocytes to mature adipocytes, by reducing the
      intracytoplasmic triglyceride accumulation, an indicator of adipogenic
      differentiation, and also stimulated their aromatase activity. Melatonin
      counteracted the inhibitory effect on adipocyte differentiation and aromatase
      activity induced by MCF-7 cells in 3T3-L1 cells. The levels of cytokines in the
      co-culture media were 10 times those found in culture of 3T3-L1 cells alone.
      Melatonin decreased the concentrations of cytokines in the media and counteracted
      the stimulatory effect induced by MCF-7 cells on the cytokine levels. One
      millimolar melatonin induced a reduction in TNF-alpha, IL-6, and IL-11 mRNA
      expression in MCF-7 and 3T3-L1 cells. The findings suggest that melatonin may
      play a role in the desmoplastic reaction in breast cancer through a
      downregulatory action on the expression of antiadipogenic cytokines, which
      decrease the levels of these cytokines. Lower levels of cytokines stimulate the
      differentiation of fibroblasts and decrease both aromatase activity and
      expression, thereby reducing the number of estrogen-producing cells proximal to
      malignant cells.

PMID- 22151119
TI  - Ureteral replacement with appendix in pediatric renal transplantation.
AB  - Ureteral necrosis is an uncommon complication following RT which can adversely
      affect outcome. Even though authors agree that the native ureter ought to be
      preserved, there are cases in which graft function can only be salvaged by
      ureteral substitution. The scant references in the literature on the use of the
      appendix for left ureteral replacement in children prompted us to report the
      following two cases in whom the technique was employed and to assess the
      evolution of graft function in these patients.

PMID- 22151120
TI  - Hypothalamic deep brain stimulation for the treatment of chronic cluster
      headaches: a series report.
AB  - The objective of this study was to introduce a new surgical treatment for drug
      resistant chronic cluster headaches (CH). Because recent functional studies
      suggested that a hyperactivity of the posterior hypothalamus might be the primary
      cause of Cluster Headaches (CH) bouts, we designed a prospective study to explore
      the therapeutic effectiveness of chronic high-frequency stimulation of this
      region for the treatment of CH. Nine electrodes were stereotactically implanted
      in the posterior hypothalamus in eight patients suffering from intractable
      chronic CH. The stereotactic coordinates of the targeted area were 3 mm behind
      the mid-commissural point, 5 mm below the mid-commissural point, and 2 mm lateral
      from the midline. Since initiating this treatment in our center, all of the eight
      patients have improved. Steroid administration has been progressively withdrawn.
      All of the patients reported that they were pain-free at 1-26 months of follow
      up. Three of the eight patients were pain-free without any medication while five
      of the eight required low doses of methysergide and/or verapamil. No noxious side
      effects from chronic high-frequency hypothalamic stimulation have been observed
      nor have we encountered any acute complications from the implant procedure.
      Tolerance was not observed. We conclude that these preliminary results indicate
      that hypothalamic stimulation is safe and effective for the treatment of drug
      resistant, chronic CH. In addition, these data confirm the "central" pathogenesis
      for chronic CH.

PMID- 22151121
TI  - Failure of chronic pallidal stimulation in dystonic patients is a medical
      emergency.
AB  - Deep brain stimulation (DBS) therapy is a continually expanding field of
      functional neurosurgery for the treatment of movement disorders and neuropathic
      pain. However, occurrence of adverse events related to implanted hardware cannot
      be ignored, particularly in patients with dystonic conditions. We report on two
      such patients who required emergency hospital admission and pulse generator re
      implantation following sudden and unexpected cessation of DBS effectiveness
      resulting from battery failure.

PMID- 22151122
TI  - Spinal cord stimulator adjustment to maximize implanted battery longevity: a
      randomized, controlled trial using a computerized, patient-interactive
      programmer.
AB  - Internally powered, implanted pulse generators (IPGs) have been an important
      advance in spinal cord stimulation for the management of pain, but they require
      surgical replacement, with attendant cost and risk, when the implanted battery is
      depleted. Battery life is determined by the programmed settings of the implant,
      but until now the technical means to optimize settings for maximal battery life,
      delaying surgical replacement as long as possible, Materials and Methods.  We
      have developed a patient-interactive, computerized programmer for use with IPGs.
      It has been designed for easy operation and comprehensive data management, which
      have not been features of the standard programmers available until now. It
      automatically and rapidly presents to the patient a sequence of settings (contact
      combinations and pulse parameters) specified by the practitioner. Test results
      are analyzed and sorted to determine the optimal settings by multiple criteria,
      including battery life. In the present study we used new, improved algorithms to
      estimate battery life.  We have compared the computerized, patient-interactive
      system with standard practitioner-operated, manual programming methods in a
      randomized, controlled trial in 44 patients at two study centers.  In 95% of
      patients (41/43), the computerized, patient-interactive system identified new
      settings with improved estimated battery life (and corresponding anticipated cost
      savings) which had not been recognized as such using manual methods. The
      estimated battery life for the setting chosen by each patient using manual
      methods averaged 25.4 +/- 49.5 (mean +/- standard deviation) months; the longest
      battery life identified by computerized methods averaged 55.0 +/- 71.7, a 2.2
      fold or 29.6 month improvement. Seventy-two percent of patients (31/43) achieved
      better battery life at settings with technical results (visual analog scale
      rating of overlap or coverage of pain by stimulation paresthesias) equal or
      superior to those achieved by manual methods. The overall improvement over the
      setting chosen by manual methods was 1.41-fold or 10.5 months; averaged by
      patient, the improvement was 1.63-fold. Estimated cost savings averaged just over
      one-third. As reported previously, the new system also yields significantly (p <
      0.0001) better technical results than traditional, manual methods in achieving
      coverage of pain by stimulation paresthesias; the very best technical results
      were achieved at some expense in estimated battery life (assuming the same
      frequency of use). We conclude that significant potential savings in longevity of
      the implanted battery are possible in the majority of patients with implanted
      spinal cord stimulators, but have not been realized until now for lack of
      appropriate methods. Computerized, patient-interactive programming addresses this
      problem and allows optimization of estimated battery life along with other
      treatment goals. Long-term clinical followup will be required to establish the
      full magnitude of the resulting savings.

PMID- 22151123
TI  - Blood flow increase by cervical spinal cord stimulation in middle cerebral and
      common carotid arteries.
AB  - The effect of spinal cord stimulation (SCS) on cerebral blood flow (CBF) has, in
      the past, been evaluated by semiquantitative techniques, but has not been used to
      treat CBF diseases. The aim of this study was to assess the effect of cervical
      SCS on regional blood flow by both semiquantitative and quantitative methods.
      Thirty-five patients with cervical SCS-implanted devices were enrolled. The
      following parameters were measured before and after cervical SCS: systolic and
      diastolic velocity (cm/s) in the middle cerebral artery (MCA) by transcranial
      Doppler (TCD) and volume blood flow quantification (ml/min) in the common carotid
      artery (CCA) by color Doppler. During cervical SCS there was a significant and
      bilateral increase in systolic (21%) and diastolic (26%) velocity in the MCA and
      in CCA blood flow (50%). We conclude that cervical SCS increases blood flow in
      the middle cerebral artery and common carotid artery. The consistent increase
      supports the potential usefulness of cervical SCS as an adjuvant treatment for
      cerebral blood flow diseases.

PMID- 22151124
TI  - A new technique of "midline anchoring" in spinal cord stimulation dramatically
      reduces lead migration.
AB  - Spinal cord stimulation (SCS) is a popular method of treatment of chronic pain.
      Unfortunately, migration of the lead continues to be a serious complication of
      this therapy. In an attempt to reduce lateral migration of the SCS lead, we
      performed a retrospective assessment of a new technique of percutaneous lead
      placement. This new method of "midline anchoring" of the lead using the plica
      mediana dorsalis was tested against conventional technique in a retrospective
      study involving 122 trials and 91 implants of SCS over a period of five years.
      The use of "midline anchoring" resulted in a decrease in lead migration from 23%
      to 6% after trial insertion and from 24% to 7% after implantation. We conclude
      that "midline anchoring" of the SCS lead is an effective method of preventing
      lead migration.

PMID- 22151125
TI  - First Clinical Experience with BION Implants for Therapeutic Electrical
      Stimulation.
AB  - The objective of this study was to assess the usability and safety of BION
      injectable neuromuscular microstimulators for therapeutic electrical stimulation
      (TES) to treat two conditions involving disuse atrophy: poststroke shoulder
      subluxation in hemiplegic subjects and knee osteoarthritis. Clinicians were
      provided with PC-based software to track implants and to design the exercise
      programs. Subjects self-administered TES (3 sessions/day, 10-30 min/session) for
      6 or 12 weeks. Outcome measures included subluxation for the shoulder study and
      knee function and pain for the osteoarthritis study. All subjects were
      comfortable with the BION equipment and therapy; eight of 10 experimental
      subjects elected to continue treatment after the study period. Shoulder
      subluxation was reduced by 55% +/- 54%; knee function was enhanced by 65% +/-
      24%; and knee pain decreased by 78% +/- 18%. The devices did not migrate and did
      not cause inflammation or pain. Thresholds were stable over time. We conclude
      that the use of BION implants to exercise atrophic muscles was well-accepted and
      provided effective rehabilitation in these two clinical conditions.

PMID- 22151126
TI  - Proprioceptive neuromuscular facilitation in combination with electrical
      stimulation: combined treatment in comparison to each treatment alone.
AB  - The objective of the study was a quantitative examination of Proprioceptive
      Neuromuscular Facilitation (PNF) exercise in simultaneous combination with FES of
      lower extremity muscles in comparison to voluntary movement, training with PNF
      alone, or training with FES alone. Two subjects were monitored during a one-month
      rehabilitation period. The PNF pattern included flexion, adduction, and external
      rotation of the hip, knee flexion, and dorsiflexion with inversion of the ankle,
      a pattern similar to the swing phase of walking. Quantitative measurements were
      conducted by using goniometers on the hip, knee, and ankle joints. Major changes
      were found in the hip angle. Improvements in goniograms were greatest during the
      first week, smaller during the second week, and showed only a slight positive
      trend in the last two weeks. The measurements made two months after the start of
      training showed somewhat lower values in comparison to previous sessions.

PMID- 22151127
TI  - Development of an isokinetic functional electrical stimulation cycle ergometer.
AB  - An isokinetic functional electrical stimulation leg cycle ergometer (iFES-LCE)
      was developed for individuals with spinal cord injury (SCI). The iFES-LCE was
      designed to allow cycle training over a broad range of pedalling cadences (5-60
      rev/min) to promote both muscular strength and cardiorespiratory fitness. A
      commercially available motorized cycle ergometer was integrated with a custom
      built FES system, a laptop computer, and a specialized chair that restricted
      lateral leg movements. Sample biomechanical data were collected from an SCI
      subject performing FES cycling to demonstrate the iFES-LCE's performance
      characteristics. Calibration of the iFES-LCE system revealed a linear
      relationship between torque applied to the axle of the motorized ergometer and
      the braking motor current generated to maintain velocity. Performance data
      derived from iFES-LCE motor torque agreed closely with similar data collected
      using strain-gauge instrumented pedals (cross-correlations = 0.93-0.98). The iFES
      LCE was shown to work well across a range of pedaling cadences. We conclude that
      the new iFES-LCE system may offer improved training potential by allowing cycling
      over a broad range of pedaling cadences, especially low cadence. This device also
      improves upon the accuracy of other ergometers by adjusting for the passive load
      of the legs.

PMID- 22151128
TI  - Letter to the editor.

PMID- 22151129
TI  - Trend of severe abdominal injuries from bicycle accidents in children: a
      preventable condition.
AB  - AIM: Bicycle riding is a common recreational and sport activity enjoyed by many
      children. Bicycle accidents are a common cause of abdominal injuries. We aim to
      establish the trend and the associated risk factor(s) of bicycle-related
      abdominal injuries. METHODS: A retrospective review of all children admitted
      following bicycle accidents to a single tertiary referral centre was carried out
      over an approximately 5-year period. The data were tabulated and regression
      analyses were carried out. RESULTS: Over the study period, 196 children were
      admitted into the Emergency Department. Abdominal injuries (16%) were the third
      largest group after orthopaedic and head injuries. There were 19 major visceral
      injuries, seven of whom underwent major surgeries. Forty-two percent (8/19) of
      these major injuries were related to stunts. Over the same period, no child with
      head injury required any surgical intervention. In addition, there was a definite
      trend that abdominal injuries were accounting for greater percentage of bicycle
      related injuries in children. CONCLUSIONS: Severe intra-abdominal trauma
      following bicycle injuries appears to be seen more often in adolescent males,
      especially when related to BMX stunts. These injuries have surpassed head
      injuries as the prime cause of morbidity from bicycle accidents. These injuries
      are largely preventable.

PMID- 22151130
TI  - Review: the development of family quality of life concepts and measures.
AB  - Historically, intervention programmes in intellectual and developmental
      disabilities have targeted the individual's special needs independent of the
      family and environmental context. This trend has been changing over the past two
      decades. This paper presents a literature review on changing trends in family
      support and the development of family quality of life (FQOL) and intellectual
      disability from a construct to a theory. The evolution of research in quality of
      life from the perspective of the individual with the disability to the family is
      described. A description of the development of FQOL measures is included,
      specifically an introduction and comparison of the two leading comprehensive
      initiatives on measuring FQOL - international FQOL project and the FQOL
      initiative of the Beach Center on Disability, in the USA. This paper provides the
      conceptual background and context to the other papers presented in this special
      issue, which focus on FQOL measurement in specific contexts.

PMID- 22151131
TI  - Reduction in hyperammonaemia by ornithine phenylacetate prevents
      lipopolysaccharide-induced brain edema and coma in cirrhotic rats.
AB  - OBJECTIVE: In liver failure, inflammation synergistically exacerbates the
      deleterious cerebral effects of ammonia. The aims were to test whether treatment
      with the ammonia-lowering agent ornithine phenylacetate (OP) and/or anti-TNF
      alpha (infliximab) prevent the deleterious brain consequences of
      lipopolysaccharide (LPS) in cirrhotic rats. DESIGN: Rats 4 weeks following bile
      duct-ligation (BDL), sham-operation (sham) and/or 7 days hyperammonemic feed
      (HD), were randomized to receive LPS (1 mg/kg) or saline, and treatment with
      either 3 days intraperitoneal injections of OP (0.6 g/kg) and/or infliximab, 10
      mg/kg. Animals were sacrificed at coma stages or at 3 h. RESULTS: In sham rats,
      both HD and LPS increased brain water, with an increase in ammonia in the former
      and brain cytokines in the latter but with no effect on consciousness. BDL + HD
      rats caused significantly higher plasma ammonia, TNF-alpha and IL-6 levels
      compared to sham. LPS significantly worsened coma stage, increased brain water
      and plasma and brain TNF-alpha. OP significantly delayed LPS-induced progression
      to coma stages (P < 0.009), reduced arterial ammonia and brain water (P < 0.001
      and P < 0.01 respectively), which was associated with a significant reduction in
      cytokines. Infliximab significantly reduced plasma and brain cytokines, but not
      brain water. OP + infliximab attenuated increase in brain water and delayed
      occurrence of coma, which was not different to OP alone. In BDL rats, OP reduced
      the expression of brain iNOS and NFkappaB. CONCLUSION: Reduction in ammonia with
      OP in cirrhotic rats prevents LPS-induced brain edema and delays coma, suggesting
      that ammonia may prime the brain to the deleterious effect of LPS, possibly
      through effects on iNOS and NFkappaB related mechanisms.

PMID- 22151132
TI  - Rapid influenza H1N1 diagnostic test: its diagnostic property.

PMID- 22151133
TI  - Right atrial mass associated with a dialysis catheter.

PMID- 22151134
TI  - Carbon dioxide laser photoablation adjunctive therapy following superficial
      lamellar keratectomy and bulbar conjunctivectomy for the treatment of
      corneolimbal squamous cell carcinoma in horses: a review of 24 cases.
AB  - OBJECTIVE:   To determine the complications and nonrecurrence rates following
      superficial lamellar keratectomy, bulbar conjunctivectomy, and adjunctive carbon
      dioxide (CO(2)) photoablation for corneolimbal squamous cell carcinoma (SCC) in
      the horse. STUDY DESIGN:   Retrospective study. Sample population  Twenty-four
      horses with corneolimbal SCC. PROCEDURE:   Medical records of horses diagnosed
      with corneolimbal SCC that was surgically excised and where CO(2) photoablation
      was used as an adjunctive therapy from 2000 to 2007 were reviewed. Signalment,
      prior therapy, tumor location and size, complications, and recurrence of SCC were
      recorded. RESULTS:   The Thoroughbred was the most commonly (25%) represented
      breed. Lesions were >10 mm in diameter in 70.8% of cases. Eight horses (33.3%)
      had neoplastic cells extending to the deep margin of the keratectomy. All horses
      were available for follow-up for an average +/- standard deviation of 40.7 +/- 25
      months. Four horses (16.7%) developed a recurrence of SCC. Three of these four
      horses underwent repeat keratectomy and CO(2) photoablation, one each, at 4
      months, 1, and 2 years following the initial procedure. One horse underwent
      enucleation 8 months following the initial procedure. CONCLUSIONS AND CLINICAL
      RELEVANCE:   As an adjunctive therapy, CO(2) photoablation was successful in
      87.5% of the horses following a single procedure and in a total of 91.7%
      following a second therapeutic application. CO(2) photoablation appears to be
      effective as an adjunctive therapy following removal of large corneolimbal SCC in
      the horse and in cases in which all tumor cells were not excised.

PMID- 22151135
TI  - Management of muscle haematomas in patients with severe haemophilia in an
      evidence-poor world.
AB  - Treatment studies in haemophilia focus on joint bleeds; however, some 10-25% of
      bleeds occur in muscles. This review addresses management of muscle haematoma in
      severe haemophilia, defines gaps in the published evidence, and presents a
      combined clinician and physiotherapist perspective of treatment modalities. The
      following grade 2C recommendations were synthesized: (i) Sport and activity
      should be based on individual factor levels, bleeding history and physical
      characteristics, (ii) Musculoskeletal review aids the management of children and
      adults, (iii) 'Time to full recovery' should be realistic and based on known
      timelines from the healthy population, (iv) Diagnosis should be carried out by
      both a clinician and physiotherapist, (v) Severe muscle bleeds should be treated
      similarly to surgical patients: a 50% trough for 10-14 days followed by high
      level prophylaxis, (vi) Protection, rest, ice, compression and elevation should
      be implemented in the acute stage, and (vii) Physiotherapy and rehabilitation
      should be divided into: control of haemorrhage (phase 1); restoration of Range of
      Movement (ROM) and strength (phase 2); functional rehabilitation and return to
      normal living (phase 3). Recommendations specifically for inhibitor patients
      include: (i) Minor to moderate bleeds should be managed by home-treatment within
      1 h of bleed onset using either one injection of rFVIIa 270 MUg kg(-1), or two to
      three injections of rFVIIa 90 MUg kg(-1) (2-3 h intervals), or FEIBA 50-100 U kg(
      1) (repeated at 12-hourly intervals, if necessary) and (ii) Severe muscle bleeds
      should be supervised by the treatment centre and include bypassing agents until
      clinical improvement is observed.

PMID- 22151136
TI  - Close temporal coupling of neuronal activity and tissue oxygen responses in
      rodent whisker barrel cortex.
AB  - Neuronal activity elicits metabolic and vascular responses, during which oxygen
      is first consumed and then supplied to the tissue via an increase in cerebral
      blood flow. Understanding the spatial and temporal dynamics of blood and tissue
      oxygen (To2) responses following neuronal activity is crucial for understanding
      the physiological basis of functional neuroimaging signals. However, our
      knowledge is limited because previous To2 measurements have been made at low
      temporal resolution (>100 ms). Here we recorded To2 at high temporal resolution
      (1 ms), simultaneously with co-localized field potentials, at several cortical
      depths from the whisker region of the somatosensory cortex in anaesthetized rats
      and mice. Stimulation of the whiskers produced rapid, laminar-specific changes in
      To2. Positive To2 responses (i.e. increases) were observed in the superficial
      layers within 50 ms of stimulus onset, faster than previously reported. Negative
      To2 responses (i.e. decreases) were observed in the deeper layers, with maximal
      amplitude in layer IV, within 40 ms of stimulus onset. The amplitude of the
      negative, but not the positive, To2 response correlated with local field
      potential amplitude. Disruption of neurovascular coupling, via nitric oxide
      synthase inhibition, abolished positive To2 responses to whisker stimulation in
      the superficial layers and increased negative To2 responses in all layers. Our
      data show that To2 responses occur rapidly following neuronal activity and are
      laminar dependent.

PMID- 22151138
TI  - Do implantable devices improve mood? Comparisons of chronic pain patients with or
      without an implantable device.
AB  - Objective.  This descriptive study compares outcome measures of a computerized
      assessment of pain, emotional distress, and quality of life between chronic
      noncancer pain patients who have received an implantable device (spinal cord
      stimulator or intrathecal pump; N = 143) and those who have not received a device
      (N = 130). Methods.  Each patient marked the location of their pain on a body
      diagram and rated pain intensity, emotional distress, and impact of their pain on
      mood, sleep, and quality of life using a computerized pain assessment program. An
      electronic version of the Hospital Anxiety and Depression Scale (HADS) also was
      administered. Results.  No significant differences were found on the pain
      variables between the two groups. Patients with an implantable device gave lower
      ratings (less impact) on emotional distress (p < 0.05) and rated their health
      quality of life as better compared with control patients (p < 0.05). The patients
      with implantable devices also scored lower on the HADS Depression Subscale.
      Conclusion.  The results suggest that although patients with an implantable
      device seem to have more pathology and greater disability, they report less
      emotional distress and improved quality of life compared with patients with
      chronic pain without an implantable device. Future controlled trials are needed
      to establish the role that an implantable device plays in improving mood and
      quality of life.

PMID- 22151137
TI  - Natural history of severe eosinophilia with uncertain aetiology and proposals on
      a practical approach to its management.
AB  - BACKGROUND: Eosinophilia is commonly encountered during clinical practice. Some
      can be attributed to well-defined causes while others cannot. Optimal management
      of hypereosinophilia with unknown aetiology is uncertain as the natural history
      is not well described. METHODS: We retrospectively studied patients with
      hypereosinophilia (>5 * 10(9)/L) and described the characteristics, natural
      history and treatment of those with eosinophilia of uncertain aetiology. RESULTS:
      There were 141 patients with hypereosinophilia: 87 with well-defined causes, 54
      with uncertain aetiology. The latter was managed as hypereosinophilic syndrome
      (HES) (n = 5), idiopathic hypereosinophilia (IH) (n = 11), presumptive helminthic
      infection (n = 11) and reactive eosinophilia (n = 5), while 22 were
      insufficiently investigated and did not have definite working diagnoses. Their
      median age and peak eosinophil count were 64 (22 to 94) years and 10.0 (5.2-33.9)
      * 10(9)/L respectively. Forty-six per cent had symptoms attributable to
      eosinophilia, with the HES and insufficiently investigated groups having the
      highest (100%) and lowest (27%) percentages respectively. HES and IH patients
      were most extensively investigated. All 14 HES or IH patients who received
      steroids responded. All presumptive helminthic infection patients received
      mebendazole: nine responded, and two had unassessable responses. For the
      remaining patients, seven received steroids and all responded; one received
      mebendazole but defaulted; 19 were not treated: 11 resolved spontaneously. No non
      HES patients developed eosinophilia-related organ dysfunction. No mortality was
      caused by hypereosinophilia. CONCLUSIONS: Patients with hypereosinophilia of
      uncertain aetiology can be empirically managed according to working diagnoses
      derived from history taking, examination and selective investigations. Most
      patients have benign short-term outcomes, but longer monitoring is required to
      assess long-term outcomes from untreated hypereosinophilia.

PMID- 22151140
TI  - Head and neck peripheral stimulation for chronic pain report of three cases.
AB  - Neuropathic facial pain often is a very difficult problem to treat. We describe
      three cases of intractable neuropathic facial pain which were successfully
      treated with peripheral stimulation. These three cases review trialing, operative
      considerations, including cosmetic considerations, and provide some insight into
      the pathophysiology of these pain syndromes.

PMID- 22151139
TI  - Hamilton rating scale for depression-21 modifications in patients with vagal
      nerve stimulation for treatment of treatment-resistant depression: series report.
AB  - Vagal nerve stimulation (VNS) has been approved for treatment of refractory
      depression (or treatment-resistant deperssion) and bipolar disorder in Europe and
      Canada since 2001 and in United States since 2004 by the Food and Drug
      Administration. Several lines of evidence support an effective antidepressant
      effect with such treatment modality, outcomes being mainly evaluated with
      Hamilton Rating Scale for Depression (HRSD). We here report a series of nine
      patients with severe treatment-resistant deperssion. They all underwent surgical
      intervention of implantation of left vagal nerve electrode at our institute. The
      preoperative psychiatric status and postoperative clinical outcome were both
      evaluated with the 21-item version of the HRSD (HRSD(21) ). Five out of nine
      patients, having at least one-year follow-up, were responders (>=50% reduction of
      HRSD scoring) and four of these also were remitters (HRSD < 10). One patient with
      bipolar II disorder and one patient with melancholic depression did not
      significantly benefit from the procedure; the latter three patients have follow
      ups shorter than three months and one of them meets the remittance criteria;
      nonetheless, for the other two , HRSD(21)  score is gradually decreasing with
      time.

PMID- 22151141
TI  - Subcutaneous peripheral nerve stimulation treatment for chronic pelvic pain.
AB  - Two cases of chronic pelvic pain of unknown etiology with symptoms referable to
      the low abdominal wall are presented. These patients are often difficult to
      manage because of multiple causes and multiple pathways for pain transmission
      from the pelvis. In these cases, the patients' complaints were refractory to
      medication management, as well as diagnostic and therapeutic nerve blockade.
      After careful evaluation, a successful trial of peripheral nerve stimulation was
      followed by permanent implantation of low abdominal subcutaneous leads and a
      pulse generator device. The patients reported excellent relief of their chronic
      pelvic pain. The use of neuromodulation via peripheral stimulation deserves
      further investigation as an alternative to spinal cord stimulation for chronic
      pelvic pain.

PMID- 22151142
TI  - Spinal cord stimulation for chronic pain: causes of long-term paddle-lead
      failure.
AB  - Objectives.  This study is to evaluate long-term lead failure in spinal cord
      stimulation. Materials and Methods.  One hundred and seven patients with
      permanently implanted spinal cord stimulators were studied for 14 years. All
      suspected paddle-lead failures were studied prospectively using preoperative
      radiography and intraoperative electric interrogation. Lead failure was defined
      as complete loss of electric stimulation due to lead malfunction. Primary lead
      failure was defined as first lead failure after permanent implantation of a new
      lead and recurrent lead failure was defined as any lead failure after any lead
      replacement. Results.  Primary lead failure occurred in 14.9% and recurrent lead
      failure in 56.2%. Two (12.5%) of the primary failures and two (22.2%) of the
      recurrent failures were due to lead fractures. The mean time to primary lead
      failure was 37.9 months and to recurrent lead failure was 23.7 months.
      Conclusion.  The incidence of primary lead failure remains low at 14.9% in the
      long run, but it is a significant adverse risk factor for recurrent paddle-lead
      failure. Great care should be undertaken to prevent lead failures by appropriate
      anchoring.

PMID- 22151143
TI  - Efficacy of a Single, Percutaneous, Across Midline, Octrode(r) Lead Using a
      "Midline Anchoring" Technique in the Treatment of Chronic Low Back and/or Lower
      Extremity Pain: A Retrospective Study.
AB  - Introduction.  Spinal cord stimulation is a widely used treatment modality for
      chronic pain, especially failed back surgery syndrome. However, migration of the
      lead or leads, coverage of axial pain, and the selection of an optimal system
      configuration continue to be subjects for serious debate. Materials and Methods. 
      A retrospective study of the use of the method of "midline anchoring" of a single
      Octrode(r) lead, in 54 patients with low back and/or lower extremity pain, was
      done to assess the efficacy of this technique. Results.  During the study period
      of 9.3 months, only a 4% revision rate was reported. Reduction in pain of more
      than 50% and individual patient satisfaction scores were very high (85% and 87%,
      respectively). Successful bilateral pain coverage was obtained with a single
      Octrode(r) lead. The lower extremities and buttocks area were captured in 89% of
      the patients. Axial pain coverage was achieved in the majority of the patients,
      with 71% reporting adequate coverage of the upper lumbar spine. A "guarded
      cathode" array was used in the vast majority of the cases, with a relatively low
      position of the lead. Conclusions.  "Midline anchoring" of the spinal cord
      stimulation lead is an effective implantation technique, allowing the use of a
      single, percutaneous, Octrode(r) lead, while preventing lead migration and
      allowing capture of axial and lower extremity pain, unilateral as well as
      bilateral. This study revives the idea of a single lead as a possible optimal
      configuration.

PMID- 22151144
TI  - Change in cerebral perfusion of patients with coma after treatment with right
      median nerve stimulation and hyperbaric oxygen.
AB  - Background.  Survival rates after acute brain injury have improved, but
      persistent coma continues to be a major clinical problem. Objective.  We analyzed
      changes in cerebral perfusion after treatment with right median nerve stimulation
      (MNS) or MNS with hyperbaric oxygen (MNS + HBO), two noninvasive therapies that
      have shown promise in this patient population. Methods.  During the period this
      series of patients was treated, decision-makers were offered the option of MNS
      for six weeks (continued for maximum of three months if patient responded) or MNS
      + HBO (HBO given during the first six weeks of MNS). Results.  Of 41 patients, 14
      received MNS only and 27 received MNS + HBO. Pre- and posttreatment single photon
      emission computed tomography scans showed increased cerebral perfusion in 29
      patients, with perfusion unchanged in nine patients and decreased in three
      patients. A total of 25 patients improved in one or more clinical measures, with
      13 regaining consciousness. With univariate analysis, the odds ratio for
      improvement with MNS + HBO relative to MNS was 4.40 (95% confidence intervals:
      1.06-18.36). Multivariate analysis indicated that MNS + HBO was significantly
      related to increased cerebral perfusion compared with MNS alone (odds ratio =
      8.44, 95% confidence intervals: 1.34-52.97). Conclusion.  The combination of MNS
      + HBO is more likely to result in improved cerebral perfusion than MNS alone.
      Randomized prospective trials evaluating MNS, especially with adjunct HBO, are
      needed to clarify clinical indications and most effective treatment schemes.

PMID- 22151145
TI  - Direction and predictive factors for the shift of brain structure during deep
      brain stimulation electrode implantation for advanced Parkinson's disease.
AB  - Objectives.  The aims of this study were to clarify the direction and degree of
      brain shift, and to determine the predictive factors for a brain shift during
      deep brain stimulation (DBS) of the subthalamic nucleus (STN). Materials and
      Methods.  To evaluate the brain shift during bilateral STN-DBS, the position of
      the anterior commissure (AC), posterior commissure (PC), midcommissure point
      (MC), and tip of the frontal lobe and anterior horn of the lateral ventricle were
      calculated pre- and poststereotactic operations in the three-dimensional
      direction employing special software (Leksell SurgiPlan). To determine the
      predictive factors for a brain shift, patient's age, operation hours, width of
      the third ventricle, bicaudate index (BCI), and cella media index (CMI) were
      compared with the shift of MC. Results.  In 50 patients, the MC shifted mainly in
      the posterior direction (y-axis: 1.27 +/- 0.7 mm), and the shifts in the inferior
      direction (z-axis: 0.11 +/- 0.43 mm) and lateral direction (x-axis: 0.02 +/- 0.39
      mm) were small. The shift of the MC in the posterior direction correlated well
      with the shift of the tip of the anterior lobe and anterior horn. Among the
      predictive factors examined, namely, the patient's age, operation hours, width of
      the third ventricle, BCI, and CMI, only the CMI showed a correlation with the
      shift of the MC (r = 0.42, p < 0.01, Pearson's correlation coefficient; and p <
      0.05, logistic regression analysis). Conclusions.  In bilateral STN-DBS, brain
      shift occurred mainly in the posterior direction, and the CMI is useful for the
      prediction of a brain shift. Enlargement of the body part of the lateral
      ventricle is the most reliable factor for predicting a brain shift.

PMID- 22151146
TI  - Intrathecal Drug Delivery Device Infection and Meningitis due to Mycobacterium
      Fortuitum: A Case Report.
AB  - Intrathecal drug delivery device infection with Mycobacterium fortuitum has not
      been reported previously. We report a case of an implanted baclofen pump
      infection and associated mycobacterium meningitis due to Mycobacterium fortuitum.
      The entire pump system was removed and the patient was treated successfully with
      a prolonged regimen of antibiotics.

PMID- 22151147
TI  - Development and experimental identification of a biomechanical model of the trunk
      for functional electrical stimulation control in paraplegia.
AB  - Objectives.  Theoretic modeling and experimental studies suggest that functional
      electrical stimulation (FES) can improve trunk balance in spinal cord injured
      subjects. This can have a positive impact on daily life, increasing the volume of
      bimanual workspace, improving sitting posture, and wheelchair propulsion. A
      closed loop controller for the stimulation is desirable, as it can potentially
      decrease muscle fatigue and offer better rejection to disturbances. This paper
      proposes a biomechanical model of the human trunk, and a procedure for its
      identification, to be used for the future development of FES controllers. The
      advantage over previous models resides in the simplicity of the solution
      proposed, which makes it possible to identify the model just before a stimulation
      session (taking into account the variability of the muscle response to the FES).
      Materials and Methods.  The structure of the model is based on previous research
      on FES and muscle physiology. Some details could not be inferred from previous
      studies, and were determined from experimental data. Experiments with a
      paraplegic volunteer were conducted in order to measure the moments exerted by
      the trunk-passive tissues and artificially stimulated muscles. Data for model
      identification and validation also were collected. Results.  Using the proposed
      structure and identification procedure, the model could adequately reproduce the
      moments exerted during the experiments. The study reveals that the stimulated
      trunk extensors can exert maximal moment when the trunk is in the upright
      position. In contrast, previous studies show that able-bodied subjects can exert
      maximal trunk extension when flexed forward. Conclusions.  The proposed model and
      identification procedure are a successful first step toward the development of a
      model-based controller for trunk FES. The model also gives information on the
      trunk in unique conditions, normally not observable in able-bodied subjects (ie,
      subject only to extensor muscles contraction).

PMID- 22151148
TI  - Costs related to promoting breastfeeding among urban low-income women.
AB  - OBJECTIVE: To describe the costs of providing support to breastfeeding low-income
      women and compares costs to cost offsets of the intervention. DESIGN: Secondary
      analysis of data from a randomized controlled trial of an intervention to promote
      breastfeeding among low-income women with full-term infants. SETTING: A
      university hospital and a community hospital in Baltimore, Maryland.
      PARTICIPANTS: Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC) eligible breastfeeding women (N = 328) were randomized to usual
      care or the community health nurse/peer counselor intervention. METHODS: The
      researchers collected and described personnel and mileage costs over the entire
      duration of the intervention (24 weeks). Researchers also compared (using t
      tests) change in resources associated with breastfeeding including the number of
      clinic visits, hospital nights, emergency room visits, prescriptions, and formula
      feedings per day up to 12 weeks. RESULTS: The cost of the personnel and travel
      required for the intervention was $296 per woman. The use of medical care and
      number of formula feedings per day were similar for the intervention and usual
      care groups. When differences in use of medical care and formula feeding were
      statistically significant, the intervention group used fewer resources.
      CONCLUSION: Support for breastfeeding by community health nurses and peer
      counselors is partially offset by reducing medical care utilization and formula
      feeding costs.

PMID- 22151149
TI  - Investigating conservation of the albaflavenone biosynthetic pathway and CYP170
      bifunctionality in streptomycetes.
AB  - Albaflavenone, a tricyclic sesquiterpene antibiotic, is biosynthesized in
      Streptomyces coelicolor A3(2) by enzymes encoded in a two-gene operon. Initially,
      sesquiterpene cyclase catalyzes the cyclization of farnesyl diphosphate to the
      terpenoid epi-isozizaene, which is oxidized to the final albaflavenone by
      cytochrome P450 (CYP)170A1. Additionally, this CYP is a bifunctional enzyme,
      being able to also generate farnesene isomers from farnesyl diphosphate, owing to
      a terpene synthase active site moonlighting on the CYP molecule. To explore the
      functionality of this operon in other streptomycetes, we have examined culture
      extracts by GC/MS and established the presence of albaflavenone in five
      Streptomyces species. Bioinformatics examination of the predicted CYP170 primary
      amino acid sequences revealed substitutions in the CYP terpene synthase active
      site. To examine whether the terpene synthase site was catalytically active in
      another CYP170, we characterized the least related CYP170 orthologue from
      Streptomyces albus (CYP170B1). Following expression and purification, CYP170B1
      showed a normal reduced CO difference spectrum at 450 nm, in contrast to the
      unusual 440-nm peak observed for S. coelicolor A3(2) CYP170A1. CYP170B1 can
      catalyze the conversion of epi-isozizaene to albaflavenone, but was unable to
      catalyze the conversion of farnesyl diphosphate to farnesene. Molecular modeling
      with our crystal structure of CYP170A1 suggests that the absence of key amino
      acids for binding the essential terpene synthase cofactor Mg(2+) may be the
      explanation for the loss of CYP170B1 bifunctionality.

PMID- 22151150
TI  - An international eDelphi study identifying the research and education priorities
      in wound management and tissue repair.
AB  - AIM: To incorporate an international and multidisciplinary consensus in the
      determination of the research and education priorities for wound healing and
      tissue repair. BACKGROUND: A compelling reason for the study is the lack of an
      agreed list of priorities for wound care research and education. Furthermore,
      there is a growth in the prevalence of chronic wounds, a growth in wound care
      products and marketing, and an increase in clinician attendance at conferences
      and education programmes. DESIGN: The study used a survey method. METHODS: A four
      round eDelphi technique was used to collect responses from an international
      population of health professionals across 24 countries. RESULTS: Responses were
      obtained from 360 professionals representing many health care settings. The top
      education priorities related to the standardisation of all foundation education
      programmes in wound care, the inclusion of wound care in all professional
      undergraduate and postgraduate education programmes, selecting dressings and the
      prevention of pressure ulcers. The top research priorities related to the
      dressing selection, pressure ulcer prevention and wound infection. conclusion:
      Professionals from different backgrounds and countries who are engaged in wound
      management share a common set of priorities for research and education. Most
      notably, the priorities identified relate to long-established clinical challenges
      in wound care and underpin the principles of good patient care practices. The
      priorities are closely allied to an ageing population and identify many
      challenges ahead for practitioners engaged in wound management services.
      RELEVANCE TO CLINICAL PRACTICE: The provision of wound care is a major investment
      of health service resources and remains a clinical challenge today. Research is
      essential to building evidence-based practice and fundamental to development of
      quality in standards of practice; education is central to achieving competence to
      deliver effective care. The determination of research and education priorities is
      therefore an absolute requirement in developing services.

PMID- 22151151
TI  - Structural properties of the reconciliation space and their applications in
      enumerating nearly-optimal reconciliations between a gene tree and a species
      tree.
AB  - INTRODUCTION: A gene tree for a gene family is often discordant with the
      containing species tree because of its complex evolutionary course during which
      gene duplication, gene loss and incomplete lineage sorting events might occur.
      Hence, it is of great challenge to infer the containing species tree from a set
      of gene trees. One common approach to this inference problem is through gene tree
      and species tree reconciliation. RESULTS: In this paper, we generalize the
      traditional least common ancestor (LCA) reconciliation to define a reconciliation
      between a gene tree and species tree under the tree homomorphism framework. We
      then study the structural properties of the space of all reconciliations between
      a gene tree and a species tree in terms of the gene duplication, gene loss or
      deep coalescence costs. As application, we show that the LCA reconciliation is
      the unique one that has the minimum deep coalescence cost, provide a novel
      characterization of the reconciliations with the optimal duplication cost, and
      present efficient algorithms for enumerating (nearly-)optimal reconciliations
      with respect to each cost. CONCLUSIONS: This work provides a new graph-theoretic
      framework for studying gene tree and species tree reconciliations.

PMID- 22151153
TI  - Public health and the promise of free trade.

PMID- 22151154
TI  - Using the commons to facilitate health communication.

PMID- 22151156
TI  - Acculturation status has a modest effect on smoking prevalence among a cohort of
      Pacific fathers in New Zealand.
AB  - OBJECTIVE: This article explores the relationship between smoking prevalence and
      acculturation among a cohort of Pacific Island fathers resident in New Zealand.
      METHODS: Overall, 766 Pacific fathers were included in the analysis. Self
      reported smoking status was assessed and compared with data from a robust
      epidemiological measure of acculturation status specifically designed for use
      amongst the Pacific population. Additional variables describing socio-demographic
      and other circumstances of the participating fathers were also incorporated in
      the analysis because of their known association with smoking behaviour. RESULTS:
      Overall, 40.3% of Pacific fathers were current smokers. Multivariable logistic
      regression showed that acculturation status was associated with smoking crude
      (p<0.001) and multivariable logistic regression models, when adjusting to socio
      demographic variables (p=0.008). CONCLUSION: Smoking rates for Pacific fathers in
      New Zealand are high. There appears to be a modest effect of acculturation on
      smoking prevalence, where those fathers with higher Pacific cultural identity
      have the lowest smoking rates. It is opined that the strength of identification
      and a holistic view of health enhances the motivations of Pacific fathers to be
      smoke-free in New Zealand. IMPLICATIONS: Strategies which maintain, enhance, and
      incorporate fathers' Pacific cultural identity may be a useful addition to
      comprehensive tobacco control strategies to reduce the prevalence of smoking in
      Pacific people living in New Zealand.

PMID- 22151157
TI  - Community screening for cardiovascular risk factors and levels of treatment in a
      rural Maori cohort.
AB  - OBJECTIVES: To document levels of cardiovascular disease (CVD), diagnosed and
      undiagnosed risk factors and clinical management of CVD risk in rural Maori.
      METHODS: Participants (aged 20-64 years), of Maori descent and self-report, were
      randomly sampled to be representative of age and gender profiles of the
      community. Screening clinics included health questionnaires, fasting blood
      samples, blood pressure and anthropometric measures. Data were obtained from
      participants' primary care physicians regarding prior diagnoses and current
      clinical management. New Zealand Cardiovascular Guidelines were used to identify
      new diagnoses at screening and Bestpractice electronic-decision support software
      used to estimate 5-year CVD risk. RESULTS: Mean age of participants (n=252) was
      45.7 +/- 0.7, 8% reported a history of cardiac disease, 43% were current smokers,
      22% had a healthy BMI, 30% were overweight and 48% obese. Hypertension was
      previously diagnosed in 25%; an additional 22% were hypertensive at screening.
      Dyslipidaemia was previously diagnosed in 14% and an additional 43% were
      dyslipidaemic at screening. Type-2 diabetes was previously diagnosed in 11%.
      Glycaemic control was achieved in only 21% of those with type-2 diabetes. Blood
      pressure and cholesterol were above recommended targets in more than half of
      those with diagnosed CVD risk factors. CONCLUSIONS: High levels of diagnosed and
      undiagnosed CVD risk factors, especially hypertension, dyslipidaemia and diabetes
      were identified in this rural Maori community. IMPLICATIONS: There is a need for
      opportunistic screening and intensified management of CVD risk factors in this
      indigenous population group.

PMID- 22151158
TI  - Factor analysis shows association between family activity environment and
      children's health behaviour.
AB  - OBJECTIVE: To characterise the family activity environment in a questionnaire
      format, assess the questionnaire's reliability and describe its predictive
      ability by examining the relationships between the family activity environment
      and children's health behaviours - physical activity, screen time and fruit and
      vegetable intake. METHOD: This paper describes the creation of a tool, based on
      previously validated scales, adapted from the food domain. Data are from 106
      children and their parents (Adelaide, South Australia). Factor analysis was used
      to characterise factors within the family activity environment. Pearson-Product
      Moment correlations between the family environment and child outcomes,
      controlling for demographic variation, were examined. RESULTS: Three factors
      described the family activity environment - parental activity involvement,
      opportunity for role modelling and parental support for physical activity - and
      explained 37.6% of the variance. Controlling for demographic factors, the scale
      was significantly correlated with children's health behaviour - physical activity
      (r=0.27), screen time (r=-0.24) and fruit and vegetable intake (r=0.34).
      CONCLUSIONS: The family activity environment questionnaire shows high internal
      consistency and moderate predictive ability. This study has built on previous
      research by taking a more comprehensive approach to measuring the family activity
      environment. IMPLICATIONS: This research suggests the family activity environment
      should be considered in family-based health promotion interventions.

PMID- 22151159
TI  - Parental behaviours, but not parental smoking, influence current smoking and
      smoking susceptibility among 14 and 15 year-old children.
AB  - OBJECTIVE: To explore whether parental behaviours related to smoking
      socialisation and parenting are associated with smoking susceptibility and
      current smoking in 14-15 year old students. METHOD: Data were sourced from the
      New Zealand 2006 Year 10 In-depth Survey, a school-based survey of 3,189
      students. Outcome measures were susceptibility to smoking and current smoking.
      Potential determinants were second-hand smoke exposure in the home, parental
      smoking, parental anti-smoking expectations, anti-smoking rules, pocket money,
      monitoring of pocket money expenditure, general rule setting and monitoring, and
      concern about education. Analysis used logistic regression to adjust for
      potential confounding factors. RESULTS: Exposure to second-hand smoke and lack of
      parental anti-smoking expectations were independently associated with smoking
      susceptibility and current smoking. Parental smoking was not independently
      associated with current smoking or susceptibility. Receiving pocket money and an
      absence of monitoring of expenditure were associated with smoking susceptibility
      and current smoking. Lack of parental rule setting was associated with smoking
      susceptibility. Findings were similar whether or not one or more parents were
      smokers. CONCLUSIONS: Not allowing smoking in the home, communicating non-smoking
      expectations to children, monitoring pocket money, and setting rules to guide
      behaviour are strategies which are likely to reduce risk of smoking uptake.
      IMPLICATIONS: The study provides evidence to inform the development of parent
      focused interventions to reduce the risk of smoking initiation by children.

PMID- 22151160
TI  - Recommendations by Queensland GPs to be more physically active: which patients
      were recommended which activities and what action they took.
AB  - OBJECTIVE: To ascertain the extent to which general practitioners in Queensland
      recommend physical activity to their patients, the types of patients they target,
      types of activities they suggest and how patients respond to the recommendations.
      METHODS: Questions designed to answer the research objectives were included in
      the Queensland Social Survey. Univariate, bivariate and logistic regression
      analyses were employed linking relevant variables with demographic data from the
      survey. RESULTS: The survey was completed by 1,261 (35.2%) people. In the
      previous year, 225 (18%) of them were recommended by a general practitioner to do
      more physical activity. These people were more likely to have a higher body mass
      index and rate their general health as fair or poor. Walking was the most common
      activity recommended (75%). Only 18% of people were not pleased to be recommended
      to take more exercise and most (67%) reported following the advice. Blue-collar
      workers and older people were less likely to follow the recommendations.
      CONCLUSIONS: General practitioners in Queensland are recommending increased
      physical activity to patients with weight problems and with medical problems.
      Patients are usually pleased to receive the advice and act upon it. IMPLICATIONS:
      General practitioners should be aware that physical activity recommendations are
      received favourably by most patients and there is potential to improve public
      health by giving physical activity advice to sedentary and/or overweight patients
      when appropriate.

PMID- 22151161
TI  - Using linkage between hospital and ABS mortality data to enhance reporting of
      deaths among Aboriginal and Torres Strait Islander peoples.
AB  - OBJECTIVE: To investigate the potential of record linkage between the Australian
      Bureau of Statistics (ABS) mortality data and the NSW Admitted Patient Data
      Collection (APDC) to improve reporting of deaths among Aboriginal and Torres
      Strait Islander peoples. METHODS: ABS mortality data for 2002 to 2006 were linked
      with APDC records for 2001 to 2006. Six algorithms were developed to enumerate
      deaths. Possible biases by age, sex and geographic remoteness were investigated.
      RESULTS: Levels of reporting ranged from baseline reporting on the ABS mortality
      data to the largest enhancement with the 'ever reported as Aboriginal or Torres
      Strait Islander' algorithm. Enhancement was more likely in females, older people
      and residents of major cities. CONCLUSIONS: Data linkage substantially improved
      reporting of Aboriginal and Torres Strait Islander deaths. An algorithm that
      includes both the number of APDC records and the number of facilities reporting a
      person as Aboriginal or Torres Strait Islander was considered most promising.
      IMPLICATIONS: Inclusion of other datasets in the enhancement process is warranted
      to further improve reporting and address possible bias produced by using APDC
      records only. Further work should take into account the possibility that a person
      may be falsely reported as Aboriginal or Torres Strait Islander or not reported
      in either hospital or death records.

PMID- 22151162
TI  - Challenges in comparing the methods and findings of cohort studies of oral
      health: the Dunedin (New Zealand) and Pelotas (Brazil) studies.
AB  - OBJECTIVE: to systematically compare methods and some findings from two
      prospective cohort studies of oral health. METHODS: This paper describes and
      compares two such population-based birth cohort studies of younger adults: the
      Dunedin Multidisciplinary Health and Development Study (conducted in New
      Zealand); and the 1982 Pelotas Birth Cohort Study (conducted in Brazil). RESULTS:
      The two cohorts showed socio-demographic similarities and differences, with their
      gender mixes being similar, but their ethnic compositions differing markedly.
      There were some important similarities and differences in methods. Overall dental
      caries experience was higher among the Dunedin cohort. Each of the studies has
      examined the association between childhood-adulthood changes in socio-economic
      status and oral health in the mid-20s. Both studies observed the greatest disease
      experience among those who were of low SES in both childhood and adulthood, and
      the least among those who were of high SES in both childhood and adulthood. In
      each cohort, disease experience in the upwardly mobile and downwardly mobile
      groups lay between those two extremes. CONCLUSIONS AND IMPLICATIONS: There are
      important similarities and differences in both methods and findings. While the
      need for a degree of methodological convergence in future is noted, the two
      studies are able to use each other as replicate samples for research into chronic
      oral conditions.

PMID- 22151163
TI  - Validity of self-reported height and weight and derived body mass index in middle
      aged and elderly individuals in Australia.
AB  - BACKGROUND: Body mass index (BMI) is an important measure of adiposity. While BMI
      derived from self-reported data generally agrees well with that derived from
      measured values, evidence from Australia is limited, particularly for the
      elderly. METHODS: We compared self-reported with measured height and weight in a
      random sample of 608 individuals aged >= 45 from the 45 and Up Study, an
      Australian population-based cohort study. We assessed degree of agreement and
      correlation between measures, and calculated sensitivity and specificity to
      quantify BMI category misclassification. RESULTS: On average, in males and
      females respectively, height was overestimated by 1.24 cm (95% CI: 0.75-1.72) and
      0.59 cm (0.26-0.92); weight was underestimated by 1.68 kg (-1.99- -1.36) and 1.02
      kg (-1.24- -0.80); and BMI based on self-reported measures was underestimated by
      0.90 kg/m2 (-1.09- -0.70) and 0.60 kg/m2 (-0.75- -0.45). Underestimation
      increased with increasing measured BMI. There were strong correlations between
      self-reported and measured height, weight and BMI (r=0.95, 0.99 and 0.95,
      respectively, p<0.001). While there was excellent agreement between BMI
      categories from self-reported and measured data (kappa=0.80), obesity prevalence
      was underestimated. Findings did not differ substantially between middle-aged and
      elderly participants. CONCLUSIONS: Self-reported data on height and weight
      quantify body size appropriately in middle-aged and elderly individuals for
      relative measures, such as quantiles of BMI. However, caution is necessary when
      reporting on absolute BMI and standard BMI categories, based on self-reported
      data, particularly since use of such data is likely to result in underestimation
      of the prevalence of obesity.

PMID- 22151164
TI  - Psychosocial job adversity and health in Australia: analysis of data from the
      HILDA Survey.
AB  - OBJECTIVE: This study examines measures of psychosocial job quality developed
      from the Household Income and Labour Dynamics in Australia (HILDA) Survey, and
      reports on associations with physical and mental health. METHODS: The study used
      seven waves of data from the HILDA Survey with 5,548 employed respondents.
      Longitudinal random-intercept regression models assessed the association of time
      varying and between-person measures of psychosocial job quality job adversity
      with physical and mental health. RESULTS: Respondents' specific experience of
      psychosocial job adversity, except marketability, was associated with increased
      risk of mental health problems, whereas the association between psychosocial job
      adversity and physical health was largely driven by differences between people.
      CONCLUSIONS AND IMPLICATIONS: Moving into jobs with different psychosocial
      quality is associated with changes in mental health. In contrast, individuals
      with poor physical health show an increased propensity to work in poor-quality
      jobs but it seems that changes in physical health are not as strongly tied to
      changes in job quality. Differences in the relationship between physical and
      mental health and psychosocial job quality have implications for the design of
      employment, health and social policy. The HILDA Survey is an important resource
      for policy development in Australia, and the availability of valid measures of
      psychosocial of job quality will enhance its use to better understand this
      important determinant and correlate of health.

PMID- 22151165
TI  - In praise of inequality? 'Happy Planet' performance and its determinants.

PMID- 22151166
TI  - Promoting stair climbing: the importance of consistent practice when conducting
      and reviewing interventions.

PMID- 22151167
TI  - Health status of Thai migrants in Brisbane: findings from a cross-sectional
      investigation.

PMID- 22151168
TI  - Uncertainty and variability in influenza cost-effectiveness models.

PMID- 22151169
TI  - Wind, dust dispersal and risk of contamination at Alice Springs.

PMID- 22151170
TI  - Cyclone Yasi: a Cairns Base Hospital experience.

PMID- 22151171
TI  - Improved iodine status in breastfeeding women following mandatory fortification.

PMID- 22151172
TI  - Rise in bicycle-related injury hospitalisation rates in middle-aged adults, 2000
      09.

PMID- 22151173
TI  - Validity of claims in a disclaimer.

PMID- 22151174
TI  - Response to: a complex Aboriginal health project and the challenges for
      evaluation.

PMID- 22151177
TI  - Abstracts of Sepsis 2011. Beijing, China. October 26-28, 2011.

PMID- 22151175
TI  - Loneliness and social isolation among older people: the views of community
      organisations and groups.

PMID- 22151178
TI  - Benchmarking of the 2010 BioCreative Challenge III text-mining competition by the
      BioGRID and MINT interaction databases.
AB  - BACKGROUND: The vast amount of data published in the primary biomedical
      literature represents a challenge for the automated extraction and codification
      of individual data elements. Biological databases that rely solely on manual
      extraction by expert curators are unable to comprehensively annotate the
      information dispersed across the entire biomedical literature. The development of
      efficient tools based on natural language processing (NLP) systems is essential
      for the selection of relevant publications, identification of data attributes and
      partially automated annotation. One of the tasks of the Biocreative 2010
      Challenge III was devoted to the evaluation of NLP systems developed to identify
      articles for curation and extraction of protein-protein interaction (PPI) data.
      RESULTS: The Biocreative 2010 competition addressed three tasks: gene
      normalization, article classification and interaction method identification. The
      BioGRID and MINT protein interaction databases both participated in the
      generation of the test publication set for gene normalization, annotated the
      development and test sets for article classification, and curated the test set
      for interaction method classification. These test datasets served as a gold
      standard for the evaluation of data extraction algorithms. CONCLUSION: The
      development of efficient tools for extraction of PPI data is a necessary step to
      achieve full curation of the biomedical literature. NLP systems can in the first
      instance facilitate expert curation by refining the list of candidate
      publications that contain PPI data; more ambitiously, NLP approaches may be able
      to directly extract relevant information from full-text articles for rapid
      inspection by expert curators. Close collaboration between biological databases
      and NLP systems developers will continue to facilitate the long-term objectives
      of both disciplines.

PMID- 22151180
TI  - Pediatric liver-kidney transplantation for hepatorenal fibrocystic disease from a
      living donor.
AB  - The indications for and the timing of LT and/or KT for the patients with HRFCD
      are based on the severity of liver and kidney involvement. Most organs come from
      living donors, because the number of deceased donors is extremely low in Japan.
      Therefore, patients with HRFCD may need two organs from living donors. Four
      patients with HRFCD underwent living donor LT and KT from a single donor. The
      type of transplantation included combined LKT in one case, sequential LKT in two
      cases, and sequential KLT in one case. Although the case of combined LKT died
      because of sepsis, the other cases were doing well. Sequential LKT was
      successfully performed at the proper timing for each transplant; however, both of
      the donors suffered from a gastroduodenal ulcer after liver donation because of
      the psychological burden related to the relatively short period between two
      donations. In conclusion, living donation for LKT with cautious surgical
      procedures is not harmful for donors and recipients. However, changes in the
      allocation system established for deceased donors for HRFCD should be considered
      to avoid the need for two organ donations from the same living donor.

PMID- 22151179
TI  - Genotype-informed estimation of risk of coronary heart disease based on genome
      wide association data linked to the electronic medical record.
AB  - BACKGROUND: Susceptibility variants identified by genome-wide association studies
      (GWAS) have modest effect sizes. Whether such variants provide incremental
      information in assessing risk for common 'complex' diseases is unclear. We
      investigated whether measured and imputed genotypes from a GWAS dataset linked to
      the electronic medical record alter estimates of coronary heart disease (CHD)
      risk. METHODS: Study participants (n = 1243) had no known cardiovascular disease
      and were considered to be at high, intermediate, or low 10-year risk of CHD based
      on the Framingham risk score (FRS) which includes age, sex, total and HDL
      cholesterol, blood pressure, diabetes, and smoking status. Of twelve SNPs
      identified in prior GWAS to be associated with CHD, four were genotyped in the
      participants as part of a GWAS. Genotypes for seven SNPs were imputed from HapMap
      CEU population using the program MACH. We calculated a multiplex genetic risk
      score for each patient based on the odds ratios of the susceptibility SNPs and
      incorporated this into the FRS. RESULTS: The mean (SD) number of risk alleles was
      12.31 (1.95), range 6-18. The mean (SD) of the weighted genetic risk score was
      12.64 (2.05), range 5.75-18.20. The CHD genetic risk score was not correlated
      with the FRS (P = 0.78). After incorporating the genetic risk score into the FRS,
      a total of 380 individuals (30.6%) were reclassified into higher-(188) or lower
      risk groups (192). CONCLUSION: A genetic risk score based on measured/imputed
      genotypes at 11 susceptibility SNPs, led to significant reclassification in the
      10-y CHD risk categories. Additional prospective studies are needed to assess
      accuracy and clinical utility of such reclassification.

PMID- 22151182
TI  - Counseling patients for kidney transplantation: awkward conversations?

PMID- 22151181
TI  - Regulation of hTERT by BCR-ABL at multiple levels in K562 cells.
AB  - BACKGROUND: The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is
      the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that
      BCR-ABL is the specific target of Gleevec in CML treatment, we investigated the
      regulation of the catalytic component of telomerase, hTERT, by BCR-ABL at
      multiple levels in K562 cells. METHODS: Molecular techniques such as over
      expression, knockdown, real-time PCR, immunoprecipitation, western blotting,
      reporter assay, confocal microscopy, telomerase assays and microarray were used
      to suggest that hTERT expression and activity is modulated by BCR-ABL at multiple
      levels. RESULTS: Our results suggest that BCR-ABL plays an important role in
      regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec
      inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was
      downregulated, therefore suggesting a positive correlation between BCR-ABL and
      hTERT. Gleevec treatment inhibited hTERT at mRNA level and significantly reduced
      telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells (BCR-ABL
      negative cells). We also demonstrated that the transcription factor STAT5a plays
      a critical role in hTERT gene regulation in K562 cells. Knockdown of STAT5a, but
      not STAT5b, resulted in a marked downregulation of hTERT mRNA level, TA and hTERT
      protein level in K562 cells. Furthermore, translocation of hTERT from nucleoli to
      nucleoplasm was observed in K562 cells induced by Gleevec. CONCLUSIONS: Our data
      reveal that BCR-ABL can regulate TA at multiple levels, including transcription,
      post-translational level, and proper localization. Thus, suppression of cell
      growth and induction of apoptosis by Gleevec treatment may be partially due to TA
      inhibition. Additionally, we have identified STAT5a as critical mediator of the
      hTERT gene expression in BCR-ABL positive CML cells, suggesting that targeting
      STAT5a may be a promising therapeutic strategy for BCR-ABL positive CML patients.

PMID- 22151183
TI  - Insights into nephrologist training, clinical practice, and dialysis choice.
AB  - There is variable emphasis on dialysis-specific training among US nephrology
      fellowship programs. Our study objective was to determine the association between
      nephrology training experience and subsequent clinical practice. We conducted a
      national survey of clinical nephrologists using a fax-back survey distributed
      between March 8, 2010 and April 30, 2010 (N = 629). The survey assessed the time
      distribution of clinical practice, self-assessment of preparedness to provide
      care for dialysis patients at the time of certification examination, distribution
      of dialysis modality among patients, and nephrologists' choice of dialysis
      modality for themselves if their kidneys failed. While respondents spent 28% of
      their time caring for dialysis patients, 38% recalled not feeling very well
      prepared to care for dialysis patients when taking the nephrology certification
      examination. Sixteen percent obtained additional dialysis training after
      fellowship completion. Only 8% of US dialysis patients use home dialysis;
      physicians very well prepared to care for dialysis patients at the time of
      certification or who obtained additional dialysis training were significantly
      more likely to provide care to home peritoneal dialysis patients. Even though 92%
      of US dialysis patients receive thrice weekly in-center hemodialysis, only 6% of
      nephrologists selected this for themselves; selection of therapy for self was
      associated with dialysis modalities used by their patients. Nephrology training
      programs need to ensure that all trainees are very well prepared to care for
      dialysis patients, as this is central to nephrology practice. Utilization of
      dialysis therapies other than standard hemodialysis is dependent, in part, on
      training experience.

PMID- 22151184
TI  - The Behavior Problems Inventory-Short Form for individuals with intellectual
      disabilities: part I: development and provisional clinical reference data.
AB  - BACKGROUND: The Behavior Problems Inventory-01 (BPI-01) is an informant-based
      behaviour rating instrument that was designed to assess maladaptive behaviours in
      individuals with intellectual disabilities (ID). Its items fall into one of three
      sub-scales: Self-injurious Behavior (14 items), Stereotyped Behavior (24 items),
      and Aggressive/Destructive Behavior (11 items). Each item is rated on a frequency
      scale (0 = never to 4 = hourly), and a severity scale (0 = no problem to 3 =
      severe problem). The BPI-01 has been successfully used in several studies and has
      shown acceptable to very good psychometric properties. One concern raised by some
      investigators was the large number of items on the BPI-01, which has reduced its
      user friendliness for certain applications. Furthermore, researchers and
      clinicians were often uncertain how to interpret their BPI-01 data without norms
      or a frame of reference. METHODS: The Behavior Problems Inventory-Short Form (BPI
      S) was empirically developed, based on an aggregated archival data set of BPI-01
      data from individuals with ID from nine locations in the USA, Wales, England, the
      Netherlands, and Romania (n = 1122). The BPI-S uses the same rating system and
      the same three sub-scales as the BPI-01, but has fewer items: Self-injurious
      Behavior (8 items), Stereotyped Behavior (12 items), and Aggressive/Destructive
      Behavior (10 items). Rating anchors for the severity scales of the Self-injurious
      Behavior and the Aggressive/Destructive Behavior sub-scales were added in an
      effort to enhance the objectivity of the ratings. RESULTS: The sensitivity of the
      BPI-S compared with the BPI-01 was high (0.92 to 0.99), and so were the
      correlations between the analogous BPI-01 and the BPI-S sub-scales (0.96 to
      0.99). Means and standard deviations were generated for both BPI versions in a
      Sex-by-age matrix, and in a Sex-by-ID Level matrix. Combined sex ranges are also
      provided by age and level of ID. CONCLUSION: In summary, the BPI-S is a very
      useful alternative to the BPI-01, especially for research and evaluation purposes
      involving groups of individuals.

PMID- 22151185
TI  - Australian Paediatric Surveillance Unit study of haemoglobinopathies in
      Australian children.
AB  - AIM: The aims of this study were to determine the incidence and types of
      haemoglobinopathies in Australian children and their distribution among ethnic
      groups, and to collect information on timing of diagnosis of haemoglobinopathies
      in Australia. METHODS: Between January 2004 and March 2006, the Australian
      Paediatric Surveillance Unit asked paediatricians to report all children under 15
      years of age with a newly diagnosed haemoglobinopathy. A questionnaire requesting
      further information was forwarded to those clinicians. Carrier states such as
      thalassaemia minor were excluded. RESULTS: Eighty-four notifications of
      haemoglobinopathy were received by the Australian Paediatric Surveillance Unit,
      with 59 confirmed cases giving a national incidence of 0.74 per 100,000 children
      < 15 years of age per annum. Of 59 cases, 42 (71%) were Australian born. Twenty
      nine (35.6%) children had sickle cell disease, 17 (28.8%) had Hb H disease, six
      (10.2%) had beta-thalassaemia major and 15 (25.4%) had compound heterozygous
      conditions. One child died from sickle cell disease. Of Australian born children,
      at least 10 mothers (23.8%) and 11 fathers (26.2%) were unaware of their carrier
      status pre-partum (information unavailable for 13 mothers and 17 fathers). Only
      11 parents (18.6%) had risks of haemoglobinopathy discussed with them antenatally
      and only three cases (5.1%) were diagnosed antenatally. CONCLUSIONS: We found
      that a small but significant number of children with haemoglobinopathies are
      being born in Australia despite existing programmes of testing at-risk groups and
      neonatal screening. Haemoglobinopathies were also diagnosed in recent immigrants.
      Greater awareness of these conditions and enhancements of screening and detection
      programmes may be needed as the genetic diversity of the Australian population
      continues to develop.

PMID- 22151186
TI  - Evolution of brain impedance in dystonic patients treated by GPI electrical
      stimulation.
AB  - Deep Brain Stimulation is an effective treatment of generalized dystonia. Optimal
      stimulation parameters vary between patients. This article investigates the
      influence of electrical brain impedance and delivered current on the brain
      response to stimulation. Twenty-four patients were bilaterally stimulated in the
      globus pallidus internus through two implanted four-contact electrodes. The
      variation of brain impedance and current measurements was correlated with
      stimulation parameters, time course, and clinical outcome. When a contact was
      activated, a statistically significant and reversible decrease of brain impedance
      was found. Impedance and current values and their variations with time
      significantly differed between patients. The absolute impedance did not
      significantly correlate with the final outcome. We conclude that the reversible
      decrease of impedance reflects an adaptive long-term mechanism, which could be
      due to a plasticity phenomenon, but has no prognostic value. Impedance and
      current measurements give new complementary information for parameter adjustment
      and trouble shooting and should therefore be included in all patients' follow-up.

PMID- 22151187
TI  - N-of-1 Trials for Assessing the Efficacy of Deep Brain Stimulation in Neuropathic
      Pain.
AB  - The objective of this study is to determine the usefulness of single-patient,
      randomised, controlled trials (N-of-1 trials) in assessing the efficacy of deep
      brain stimulation (DBS) in neuropathic pain. Seven patients with various causes
      of intractable neuropathic pain underwent insertion of deep brain stimulating
      electrodes into the periventricular gray area or ventroposterolateral nucleus of
      the thalamus. Preoperatively, pain was measured using Visual Analog Scales (VAS)
      and the McGill Pain Questionnaire (MPQ). At 6 months, these pain assessments were
      repeated. At this point all patients were entered into a N-of-1 trial with the
      DBS on and off. Data were analyzed using the Wilcoxon and Student t-tests.
      Following placement of the deep brain stimulator, VAS scores were significantly
      reduced in six of seven patients. McGill Pain Scores (MPS) showed pain reduction
      in four of seven. The results of the N-of-1 trials were most similar to the MPQ
      scores and showed that three of seven patients could accurately predict whether
      the DBS was on or off. In the N-of-1 trials, the time between changing the DBS
      from on to off (or vice versa) had an effect on the results and probably
      underestimated the efficacy. We conclude that N-of-1 trials are a useful tool for
      assessing DBS efficacy.

PMID- 22151188
TI  - Spinal cord stimulation reverses pain and diarrheal episodes of irritable bowel
      syndrome: a case report.
AB  - Irritable Bowel Syndrome (IBS) is a functional gastrointestinal (GI) disorder,
      characterized by abdominal pain, altered bowel habit (diarrhea and/or
      constipation), and bloating in the absence of demonstrable organic pathology. It
      is the most common GI disorder seen in primary care and gastroenterology
      practices. Conservative therapies for IBS are directed at both pain and
      correction of altered GI motility. A small proportion of patients with IBS have
      severe or refractory symptoms and report constant pain. IBS is no longer
      considered solely a disorder of motility, but rather its clinical expression is
      viewed as dysregulation of CNS-enteric function. Symptoms of IBS cannot be
      explained entirely by changes in motility alone and may also arise from complex
      feedback and feed-forward interactions between supraspinal circuits, the spinal
      cord, and the periphery, in effect, a neuropathic process, that might be amenable
      to neuromodulation, that is, spinal cord stimulation. We present here a single
      case report of a patient with IBS who responded positively to SCS after failing
      all conservative therapies to alleviate or manage her abdominal pain and
      diarrheal episodes. Our discussion is focused on the reasons why SCS might work
      in patients with IBS.

PMID- 22151189
TI  - Electric Spinal Cord Stimulation (SCS) in the Treatment of Angina Pectoris: A
      Cost-Utility Analysis.
AB  - For the last 15 years electric spinal cord stimulation (SCS) has been employed in
      patients with confirmed ischemic heart disease who suffer from refractory angina
      pectoris despite maximum medical/surgical treatment. The purpose of this
      investigation was to assess not only the economic consequences of SCS treatment
      (cost-utility analysis) but also altered quality of life in SCS patients. The
      retrospective study includes 18 consecutive patients, six women and 12 men, with
      an average age of 56.5 years (range 50-68), submitted to implantation of a SCS
      system at Odense University Hospital. Before implantation of the SCS system, the
      patients were in a transcutaneous electric nerve stimulation (TENS) treatment 2
      11 months. At the submission all patients were in New York Heart Association
      functional group III/IV. The results are based on cost data from the year prior
      to start of TENS treatment compared with the year after implantation of the SCS
      system. Medical records of the patients were examined and data concerning use of
      general practitioners and emergency services were collected from a nationwide
      database. Quality of life data were collected using identical questionnaires
      (perception of pain, mobility, function in daily life, and physical activity)
      related to the period immediately before start of the TENS treatment and one year
      after SCS implant. Savings were found at hospital level (reduction in number of
      admissions) and for non-hospital related expenses (such as medication and visits
      at general practitioners). In addition, improvements were registered in all
      respects which constituted assessment of the quality of life of the patients. The
      study is a repetition of a similar analysis with identical results made in 1990
      and including the 16 first angina pectoris patients treated with SCS at Odense
      University Hospital. SCS is effective in reducing hospital and non-hospital
      related expenses and improving quality of life of the patients. SCS is a simple
      treatment for the patient to use. The implantation technique is not more invasive
      than permanent cardiac pacing. The decisive part of the procedure is the
      insertion of the electrode and follow-up with support and adjustments of the
      stimulation.

PMID- 22151190
TI  - Spinal cord stimulation for patients with critical limb ischemia: immediate and
      long-term clinical outcome from the prospective italian register.
AB  - The Prospective Italian Register of spinal cord stimulation (SCS) was designed to
      evaluate the clinical outcome of patients with severe peripheral arterial
      occlusive disease (PAOD) treated with SCS. Baseline data were collected for all
      patients with PAOD undergoing SCS treatment (September 1998 to February 2001) at
      34 participating centers. If, after a 2- to 3-week trial, SCS demonstrated
      significant clinical benefits, a permanent implantable pulse generator was
      implanted. Follow-up data were evaluated at 4, 8, and 12 months postimplantation.
      Overall, 250 patients (176 men, 74 women) were enrolled (mean age 72.6 +/- 17
      years) and classified by Fontaine stage. In total, 77.6% (194/250) of patients
      received a permanent implant and 43.6% (109/250) reached 1 year of follow-up.
      Fontaine stage, pain relief, free-walking interval, and drug intake improved
      significantly during follow-up. Age and Fontaine stage were significantly
      associated with major amputation. Cumulative limb survival at 1 year for the
      subgroup of Fontaine stage III patients was 82.2%. The mean number of hospital
      admissions and stay duration at 1 year postimplantation was significantly reduced
      compared with 1 year preimplant: 1.5 vs. 0.6 admissions and 27 vs. 6 days,
      respectively. Among 109 patients evaluable at 12 months, 83 (76.1%) experienced
      >=50% reduction in pain. All PAOD parameters improved significantly during follow
      up. At 12 months postimplantation, 76.1% of patients were responsive to SCS
      therapy. The reduction in the use of analgesics and the number and duration of
      hospital stays offers clear economic advantages.

PMID- 22151191
TI  - Peripheral nerve stimulation for the treatment of occipital neuralgia and
      transformed migraine using a c1-2-3 subcutaneous paddle style electrode: a
      technical report.
AB  - In this article we will discuss the treatment of Occipital Neuralgia (ON) and
      Transformed Migraine (TM) using a paddle style surgical stimulator lead. A paddle
      style electrode may have advantages to the cylindrical style in reducing
      migrations from cervical tension or anchor dislodgement. It should be considered
      in refractory "neuropathic" cervicocranial syndromes such as ON and TM before
      moving on to more aggressive surgical interventions.

PMID- 22151192
TI  - An Investigation of the Effect of Modifying Stimulation Profile Shape on the
      Loading Response Phase of Gait, during FES-Corrected Drop Foot: Stimulation
      Profile and Loading Response.
AB  - Drop foot stimulators today operate open loop with a trapezoidal stimulation
      profile. The traditionally applied profile originated as much from technological
      constraints as suitability for the physical pathology. It was proposed that by
      increasing the stimulation intensity during the loading response phase of gait,
      the ankle angle trajectory would become closer to that of normal gait and a more
      efficient heel rocker would be introduced. One patient, who used an implanted
      stimulator, was tested. Various profiles, which provided increased stimulation
      during loading response, were tried and joint angle trajectories,
      electromyograms, and footswitches were recorded. Statistical analysis was
      performed using a one way anova and posthoc Tukey tests. The experiment showed
      that increasing stimulation intensity during loading response increased the
      duration of the heel rocker. Statistical analysis revealed that this was
      significant at p = 0.05 level. Increasing stimulation intensity during loading
      response prolongs the heel rocker. This is an essential mechanism for advancement
      over the stance limb and providing shock absorption during weight acceptance,
      thus, we conclude that this improves the gait pattern of the drop foot sufferer.

PMID- 22151193
TI  - Tibialis Anterior and Soleus Withdrawal Reflexes Elicited by Electrical
      Stimulation of the Sole of the Foot during Gait.
AB  - The aim of the present study was to investigate the modulation and functional
      importance of nociceptive withdrawal reflexes elicited from the sole of the foot
      and recorded from the soleus (SOL) and tibialis anterior (TA) muscles during
      gait. Cutaneous electrical stimulation delivered at four locations of the sole of
      the foot was used to elicit the withdrawal reflex. Reflexes were recorded from
      eight healthy subjects during treadmill walking. The reflexes were elicited at
      heel-contact, during foot-flat, at heel-off, and during mid-swing. The reflexes
      evoked in TA were largest when the arch of the foot was stimulated, and smallest
      following stimulation of the heel (significant difference during stance, p <=
      0.002). The largest soleus responses were elicited when the arch of the foot was
      stimulated (significant difference compared with the fifth metatarsophalangeal
      joint, stimulation after heel-contact, p < 0.05). The TA reflex, expressed as a
      proportion of the electromyogram during unperturbed gait, was smallest during
      swing (p < 0.05, compared with stance) whereas the SOL reflex was maximal during
      swing (p < 0.05, compared with stance). The results suggest that the modulation
      of the reflex promotes an appropriate withdrawal while preserving balance and
      continuity of motion. These results may have applications in assisting gait of
      hemiplegics.

PMID- 22151194
TI  - Functional Electrical Therapy (FET): Clinical Trial in Chronic Hemiplegic
      Subjects.
AB  - Results from a clinical evaluation of Functional Electrical Therapy (FET) in
      chronic hemiplegic subjects are presented. FET is an intensive exercise that
      integrates voluntary maximized manipulation and augmented grasping by electrical
      stimulation of forearm and hand muscles. A total of 16 chronic hemiplegic
      subjects participated in a six-month long study. The subjects were divided into
      lower and higher functioning groups based on their capacity to voluntarily extend
      the wrist and fingers against gravity. Functional Electrical Therapy comprised 30
      min electrically assisted daily exercise of the paretic arm for three consecutive
      weeks. The outcome measures included Upper Extremity Function Test (UEFT), the
      Drawing Test (DT), and Modified Ashworth Scale (MAS) of spasticity. The UEFT
      objectively measured the abilities to grasp and manipulate objects during typical
      daily activities. The DT measured the ability to coordinate shoulder and elbow
      joints. The MAS assessed the tone of the paretic arm muscles. The control group
      was formed from hemiplegic subjects that received FET in their acute phase of
      hemiplegia and were evaluated in our earlier study. The results showed that FET
      slightly increases the ability to reach and grasp, and decreases absolute mean
      spasticity of chronic hemiplegic subjects. The gains in UEFT and DT were
      measurable, yet not statistically significant. The trends of UEFT and DT scores
      during the therapy (three weeks) were steeper when compared with the trend during
      follow-up (23 weeks). The changes of the trends during the study suggest that
      prolonged treatment could lead to bigger gains. We found standard deviations were
      increased towards the end of follow-up suggesting individual differences in
      response to either the treatment or the disablement process.

PMID- 22151195
TI  - Findings with Bilateral Sacral Neurostimulation: Sixty-two PNE-Tests in Patients
      with Neurogenic and Idiopathic Bladder Dysfunctions.
AB  - We performed bilateral PNE (peripheral nerve evaluation) tests to identify which
      diagnostic groups are the most likely to profit from bilateral sacral
      neuromodulation since the results published so far have been obtained exclusively
      on the basis of unilateral sacral root stimulation. In contrast to the original
      unilateral technique, we performed bilateral PNE test stimulation in 62 patients
      (36 with urinary retention symptoms and 26 with overactive detrusor; 21 with
      idiopathic and 41 with neurogenic bladder dysfunction) over 3-4 days. We used an
      advanced electrode, model #3057 (Medtronic, Inc. Minneapolis, MN). The
      stimulation amplitudes were adjusted individually for each side. Retrospectively,
      we analyzed our data according to diagnostic characteristics (retention vs.
      overactive bladder and neurogenic vs. idiopathic) of those patients who had
      positive PNE test results. The PNE test was successful in 32 patients (51.6%). Of
      these, 27 suffered from neurogenic bladder dysfunction; in five cases the cause
      was idiopathic. We conclude that bilateral PNE test stimulation with side
      specific amplitude adjustment and the use of advanced PNE electrodes led to a
      positive PNE result in 51.6% of the patients, which is a substantially increased
      response rate compared to previous studies. Of the diagnostics groups, the group
      with neurogenic bladder dysfunctions showed the highest response rate.

PMID- 22151197
TI  - Disseminated mite infection with ocular involvement in a juvenile bald eagle
      (Haliaeetus leucocephalus).
AB  - A bald eagle (Haliaeetus leucocephalus) was found unable to fly and was admitted
      to The Raptor Center (TRC). Major clinical signs were thin body condition and a
      cardiac arrhythmia. Ten days after admission to TRC, ophthalmic examination
      revealed multiple, distinct serpiginous lesions of chorioretinal atrophy in the
      ocular fundus of the right eye (OD). The bird was euthanized because of clinical
      deterioration and poor prognosis. Mites of an undetermined species were found
      histologically in the retina, episcleral tissues, lungs, and liver at the
      postmortem examination. Disseminated mite infection should be considered in the
      differential diagnosis of serpiginous chorioretinal lesions in bald eagles (H.
      leucocephalus).

PMID- 22151198
TI  - Treatment of haemophilia A and B and von Willebrand's disease: summary and
      conclusions of a systematic review as part of a Swedish health-technology
      assessment.
AB  - In an ongoing health-technology assessment of haemophilia treatment in Sweden,
      performed by the governmental agency Dental and Pharmaceutical Benefits Agency
      (TLV; tandvards-och lakemedelsformansverket), the Swedish Council on Health
      Technology Assessment (SBU; statens beredning for medicinsk utvardering) was
      called upon to evaluate treatment of haemophilia A and B and von Willebrand's
      disease (VWD) with clotting factor concentrates. To evaluate the following
      questions: What are the short-term and long-term effects of different treatment
      strategies? What methods are available to treat haemophilia patients that have
      developed inhibitors against factor concentrates? Based on the questions
      addressed by the project, a systematic database search was conducted in PubMed,
      NHSEED, Cochrane Library, EMBASE and other relevant databases. The literature
      search covered all studies in the field published from 1985 up to the spring of
      2010. In most instances, the scientific evidence is insufficient for the
      questions raised in the review. Concentrates of coagulation factors have good
      haemostatic effects on acute bleeding and surgical intervention in haemophilia A
      and B and VWD, but conclusions cannot be drawn about possible differences in the
      effects of different dosing strategies for acute bleeding and surgery.
      Prophylaxis initiated at a young age can prevent future joint damage in persons
      with haemophilia. The available treatment options for inhibitors have been
      insufficiently assessed. The economic consequences of various treatment regimens
      have been insufficiently analysed. Introduction of national and international
      registries is important.

PMID- 22151199
TI  - New erythrocyte and reticulocyte parameters on CELL-DYN Sapphire: analytical and
      preanalytical aspects.
AB  - INTRODUCTION: Extended RBC and reticulocyte parameters are useful in diagnosing
      functional iron deficiency and various other clinical conditions. The newest
      software of the CELL-DYN Sapphire measures extended RBC and reticulocyte
      parameters. The aims of the present communication were to assess the analytical
      aspects of these parameters compared with the Siemens Advia 120 analyzer, to
      study the effect of sample aging and to briefly explore their clinical usefulness
      in patients with anemia. METHODS: Blood samples were obtained from the routine
      workload of two hospital laboratories and were run on Siemens Advia and Abbott
      CELL-DYN Sapphire analyzers in parallel. Data analysis was performed using
      standard statistics. RESULTS: In total, 1416 patient samples were analyzed. There
      was close correlation in microcytic and macrocytic RBC (r(2) > 0.97) with small
      bias. The hypo- and hyperchromic RBC showed reasonable correlations, Advia 120
      giving higher values. Reticulocyte MCV showed acceptable agreement, with
      significant proportional bias (Advia 8-9% higher). CELL-DYN Sapphire MCHr
      correlated rather well with Advia CHr (r(2) > 0.91) with significant absolute
      bias. Remarkably, the correlation data differed significantly between the two
      laboratories. It was found that aging of EDTA samples had significant effect on
      most of the RBC parameters. CONCLUSIONS: The new RBC parameters of CELL-DYN
      Sapphire generally correlated well with those of Advia 120, although significant
      systematic differences were present, particularly in reticulocyte MCH and MCV.
      These differences necessitate instrument-specific reference ranges and clinical
      decision values. To minimize preanalytical effects, these parameters should be
      measured in fresh blood samples.

PMID- 22151200
TI  - Heterologous expression of green fluorescent protein in Paenibacillus larvae, the
      causative agent of American Foulbrood of honey bees.
AB  - AIMS: We aimed at expressing heterologous proteins in Paenibacillus larvae, the
      causative agent of American Foulbrood of honey bees, as a prerequisite for future
      studies on the molecular pathogenesis of P. larvae infections. METHODS AND
      RESULTS: For this purpose, we established a protocol for the transformation of
      the plasmid pAD43-25 carrying a functional GFP gene sequence (gfpmut3a) into
      different P. larvae strains representing the two most relevant P. larvae
      genotypes ERIC I and ERIC II. We determined the optimal field strength for
      electroporation and the optimal regeneration time after transformation. Stable
      GFP expression could be detected in the mutants during their entire life cycles
      and even after sporulation and re-germination. CONCLUSIONS: This method is
      suitable not only for the expression of GFP in P. larvae but also for the
      expression of heterologous proteins or GFP-tagged proteins in P. larvae. Mutants
      can be used for infection assays because GFP expression remained stable after
      sporulation and re-germination. SIGNIFICANCE AND IMPACT OF THE STUDY: This method
      provides the first true molecular tool for P. larvae and, therefore, is an
      immense advancement from what we had previously at our hands for the study of P.
      larvae pathogenesis.

PMID- 22151201
TI  - Professor charles david marsden (1938-98): an appreciation.

PMID- 22151202
TI  - Physiology of spinal cord stimulation: review and update.
AB  - Spinal cord stimulation (SCS) was an outgrowth of the well-known gate control
      theory presented by Melzack and Wall in 1965. Although the method has been used
      to treat chronic severe pain for more than three decades, very little was known
      about the physiological and biochemical mechanisms behind the beneficial effects
      until recently. We now know that SCS activates several different mechanisms to
      treat different types of pain such as neuropathic and ischemic. In general, these
      mechanisms seem most dependent on activation of only a few segments of the spinal
      cord. However, both animal studies and human observations have indicated that
      supraspinal circuits may contribute as well. In the treatment of neuropathic
      pain, intermittent SCS may give several hours of pain relief after cessation of
      the stimulation. This protracted effect indicates long-lasting modulation of
      neural activity involving changes in the local transmitter systems in the dorsal
      horns. In ischemic pain, animal experiments demonstrate that inhibition of
      afferent activity in the spinothalamic tracts, long-term suppression of
      sympathetic activity, and antidromic effects on peripheral reflex circuits may
      take part in the pain alleviation. Moderate SCS intensities seem to evoke
      sympathetic inhibition, but higher stimulation intensities may induce
      antidromically mediated release of vasoactive substances, eg, the calcitonin gene
      related peptide (CGRP), resulting in peripheral vasodilation. The anti-ischemic
      effect of SCS in angina pectoris due to intermittent coronary ischemia probably
      occurs because application of SCS appears to result in a redistribution of
      cardiac blood supply, as well as a decrease in tissue oxygen demand. Recent
      studies indicate that SCS modulates the activity of cardiac intrinsic neurons
      thereby restricting the arrythmogenic consequences of intermittent local coronary
      ischemia. The present state of knowledge is briefly reviewed and recent research
      directions outlined.

PMID- 22151203
TI  - Lead positioning and programming strategies in the treatment of complex pain.

PMID- 22151204
TI  - Spinal cord stimulation for failed back surgery syndrome: technical advances,
      patient selection and outcome.

PMID- 22151205
TI  - A Prospective Multicenter Study to Assess the Efficacy of Spinal Cord Stimulation
      Utilizing a Multi-channel Radio-frequency System for the Treatment of Intractable
      Low Back and Lower Extremity Pain. Initial Considerations and Methodology.

PMID- 22151206
TI  - Spinal Cord Stimulation for the Relief of Pain: Proceedings of a Symposium during
      the 4th International Congress of the International Neuromodulation Society,
      September 16-20, 1998, Lucerne, Switzerland.
AB  - Spinal cord stimulation has become an accepted technique used in the management
      of chronic neuropathic pain syndromes. However, a number of problematic questions
      remain unanswered. This introduction states some of these problems and
      concentrates on the problem of whether low back pain can be relieved by
      stimulation. This paper introduces subsequent contributions to this symposium,
      which offer some interesting new techniques, and attempts to answer some of the
      problems presented.

PMID- 22151207
TI  - Efficacy, safety and mechanisms of spinal cord stimulation used as an additional
      therapy for patients suffering from chronic refractory angina pectoris.

PMID- 22151208
TI  - Spinal cord stimulation for the management of complex regional pain syndromes.
AB  - The following account discusses the possible mechanisms by which spinal cord
      stimulation can control symptoms of Complex Regional Pain Syndromes. A review of
      the literature with a methodology for its incorporation in a treatment algorithm
      and associated technical aspects is suggested.

PMID- 22151209
TI  - Spinal Cord Stimulation for Complex Regional Pain Syndrome I [RSD]: a
      Retrospective Multicenter Experience from 1995 to 1998 of 101 Patients.
AB  - Objective. To evaluate effectiveness of spinal cord stimulation (SCS) applied to
      complex regional pain syndrome I (CRPS I). To analyze trends to focus the design
      of a multicenter prospective study. Design. Retrospective multicenter series, 3
      years. Outcome measures. We collected visual analog scales for pain and patient
      satisfaction data on n= 101 patients. Patients were divided into two groups:
      Group I had single-lead quadrapolar systems, Group II had dual-lead octapolar
      systems. Results. Mean pain scores decreased in both groups with a significantly
      greater decrease in Group II (p < 0.0001). 74.6% of Group II patients preferred
      multiple programming arrays with 15.5% requiring frequencies > 250Hz.; overall
      satisfaction scores were 70% in Group I and 91% in Group II (p < 0.05).
      Conclusions. SCS is an effective treatment of pain in CRPS I. Frequencies > 250Hz
      were necessary in some patients to maintain or re-establish pain control.
      Bilateral multielectrode leads appear superior with application of multiple
      arrays, permitting paresthesia steering without need for surgical revision. A
      multicenter, prospective design is needed applying dual-lead multichannel systems
      with high frequency capabilities in the treatment of CRPS I.

PMID- 22151210
TI  - Recent Advances: Sacral Nerve Root Stimulation Using a Retrograde Method of Lead
      Insertion for the Treatment of Pelvic Pain due to Interstitial Cystitis.

PMID- 22151211
TI  - Peripheral neurostimulation for control of intractable occipital neuralgia.
AB  - Objective. To present a novel approach for treatment of intractable occipital
      neuralgia using percutaneous peripheral nerve electrostimulation techniques.
      Methods. Thirteen patients underwent 17 implant procedures for medically
      refractory occipital neuralgia. A subcutaneous electrode placed transversely at
      the level of C1 across the base of the occipital nerve trunk produced
      paresthesias and pain relief covering the regions of occipital nerve pain
      Results. With follow-up ranging from 1-1/2 to 6 years, 12 patients continue to
      report good to excellent response with greater than 50% pain control and
      requiring little or no additional medications. The 13th patient (first in the
      series) was subsequently explanted following symptom resolution. Conclusions. In
      patients with medically intractable occipital neuralgia, peripheral nerve
      electrostimulation subcutaneously at the level of C1 appears to be a reasonable
      alternative to more invasive surgical procedures following failure of more
      conservative therapies.

PMID- 22151212
TI  - A study of electrode placement at the cervical and upper thoracic nerve roots
      using an anatomic trans-spinal approach.
AB  - Objective. Since 1996 we have placed temporary catheters at the cervical nerve
      roots in chronic pain patients for the treatment of radiculopathy and complex
      regional pain syndrome. We investigated the possibility of placing electrodes
      both at the cervical spinal nerve and dorsal root ganglion for the purpose of
      neuromodulation. Methods. Anatomic and technical feasibility studies were
      performed on 4 human cadavers to examine the placement of electrodes at the
      cervical nerve roots. We proposed a novel trans-spinal approach to the cervical
      and upper thoracic nerve roots. We tested various approaches and insertion
      techniques. We collected radiographic images of the essential steps involved in
      this technique. Results. Successful placement was accomplished in 3 of the 4
      cadavers at the C3, C4, C5, C6, C7, C8, T1, and T2 nerve roots. For placement at
      C5 to T2, we used a trans-spinal approach entering at the corresponding
      contralateral interlaminar space. However, due to the anatomy of the cervical
      nerve roots, vertebral artery, cervical plexus, and occiput, it was necessary to
      use a different technique for the upper cervical nerve roots. For placement at
      the C3 and C4 nerve roots, we made the initial insertion between the C1 and C2
      lamina using curved needles which were advanced in a caudal direction
      transversing the median plane of the spine to arrive at the contralateral inter
      vertebral foramen of either C3 or C4. We were unable to cannulate either C1 or C2
      in any of the cadavers. The required equipment included fluoroscopy, contrast
      dye, directable guide wires, electrodes, and curved needles. Conclusions. In
      human cadavers, a percutaneous technique was successful in the placement of
      neurostimulator electrodes at the cervical and upper thoracic nerve roots using a
      novel trans-spinal approach. New smaller electrode systems that can be placed in
      a transforaminal position safely may be needed.

PMID- 22151213
TI  - Intimate partner violence against women in western Ethiopia: prevalence,
      patterns, and associated factors.
AB  - BACKGROUND: Intimate partner violence against women is the psychological,
      physical, and sexual abuse directed to spouses. Globally it is the most pervasive
      yet underestimated human rights violation. This study was aimed at investigating
      the prevalence, patterns and associated factors of intimate partner violence
      against women in Western Ethiopia. METHODS: A cross-sectional, population based
      household survey was conducted from January to April, 2011 using standard WHO
      multi-country study questionnaire. A sample of 1540 ever married/cohabited women
      aged 15-49 years was randomly selected from urban and rural settings of East
      Wollega Zone, Western Ethiopia. Data were principally analyzed using logistic
      regression. RESULTS: Lifetime and past 12 months prevalence of intimate partner
      violence against women showed 76.5% (95% CI: 74.4-78.6%) and 72.5% (95% CI: 70.3
      74.7%), respectively. The overlap of psychological, physical, and sexual violence
      was 56.9%. The patterns of the three forms of violence are similar across the
      time periods. Rural residents (AOR 0.58, 95% CI 0.34-0.98), literates (AOR 0.65,
      95% CI 0.48-0.88), female headed households (AOR 0.46, 95% CI 0.27-0.76) were at
      decreased likelihood to have lifetime intimate partner violence. Yet, older women
      were nearly four times (AOR 3.36, 95% CI 1.27-8.89) more likely to report the
      incident. On the other hand, abduction (AOR 3.71, 95% CI 1.01-13.63), polygamy
      (AOR 3.79, 95% CI 1.64-0.73), spousal alcoholic consumption (AOR 1.98, 95% CI
      1.21-3.22), spousal hostility (AOR 3.96, 95% CI 2.52-6.20), and previous
      witnesses of parental violence (AOR 2.00, 95% CI 1.54-2.56) were factors
      associated with an increased likelihood of lifetime intimate partner violence
      against women. CONCLUSION: In their lifetime, three out of four women experienced
      at least one incident of intimate partner violence. This needs an urgent
      attention at all levels of societal hierarchy including policymakers,
      stakeholders and professionals to alleviate the situation.

PMID- 22151214
TI  - An evolutionary mechanism for diversity in siderophore-producing bacteria.
AB  - Bacteria produce a great diversity of siderophores to scavenge for iron in their
      environment. We suggest that this diversity results from the interplay between
      siderophore producers (cooperators) and non-producers (cheaters): when there are
      many cheaters exploiting a siderophore type it is beneficial for a mutant to
      produce a siderophore unusable by the dominant population. We formulated and
      analysed a mathematical model for tagged public goods to investigate the
      potential for the emergence of diversity. We found that, although they are rare
      most of the time, cheaters play a key role in maintaining diversity by regulating
      the different populations of cooperators. This threshold-triggered feedback
      prevents any stain of cooperators from dominating the others. Our study provides
      a novel general mechanism for the evolution of diversity that may apply to many
      forms of social behaviour.

PMID- 22151215
TI  - Isolation and characterization of small qnrS1-carrying plasmids from imported
      seafood isolates of Salmonella enterica that are highly similar to plasmids of
      clinical isolates.
AB  - Dissemination of plasmid-mediated quinolone resistance among pathogenic bacteria
      is a concern for public health because of decreased sensitivity to
      fluoroquinolones and increased potentials to develop high fluoroquinolone
      resistance. Two qnrS1-positive isolates of Salmonella enterica Corvallis (468)
      and Typhimurium (484) from imported seafood (Thailand and Vietnam) were tested
      for quinolone sensitivity using disk agar diffusion and the Sensititre system.
      The presence of qnr genes, qnr-carrying plasmids, and mutations in the quinolone
      resistance determining regions were also determined. Minimal inhibitory
      concentrations of nalidixic acid for isolates 468 and 484 were 8 and 16 MUg mL(
      1) , respectively, and those of ciprofloxacin were 1 and 2 MUg mL(-1),
      respectively. Disk agar diffusion indicated that isolate 468 was moderately
      resistant to moxifloxacin, and isolate 484 was resistant to moxifloxacin and
      moderately resistant to norfloxacin. Isolates 468 and 484 carried a mutation on
      parC, but not on gyrA, gyrB, or parE. Sequences of qnrS1-carrying plasmids from
      isolates 468 and 484, sized 10,039 and 10,047 bp, were nearly identical (> 99%
      similarity) to each other and to published sequences of plasmids from clinical
      isolates of Salmonella Typhimurium isolated in the United Kingdom and Taiwan,
      indicating a dissemination of qnrS1-carrying plasmids among different serovars of
      Salmonella from geographically separated sources. This is the first complete
      sequence of a qnrS1-carrying plasmid from imported seafood isolate of S.
      enterica.

PMID- 22151216
TI  - Peripheral nerve stimulation or is it peripheral subcutaneous field stimulation;
      what is in a moniker?

PMID- 22151217
TI  - Possible malfunction of electronic medical devices caused by computed tomography
      scanning.

PMID- 22151218
TI  - Neuromodulation in dystonia: current aspects of deep brain stimulation.
AB  - Among the surgical treatment options for patients with medically refractory
      dystonia chronic deep brain stimulation (DBS) of different targets in the basal
      ganglia circuitry has become one of the most important tools. The globus pallidus
      internus nowadays is the target of choice, while there is only limited experience
      with other targets. At this time, patients with primary (genetic or sporadic)
      generalized and segmental dystonia, and patients with (complex) cervical dystonia
      are thought to be the best candidates for pallidal DBS. Advantages of DBS are its
      reversibility, its adjustability, and the continuous access to modify the target
      in the basal ganglia. The present review gives an account on the development of
      surgical neuromodulation therapy for dystonia, surgical approaches, hardware
      related problems, DBS programming and patient management, and clinical outcome.
      Studies conducted according to the practices of evidence-based medicine confirm
      the results of early pilot studies. The wide majority of patients achieve
      beneficial lasting outcome at a relatively low rate of manageable side-effects.
      Along with improvement of the movement disorder, studies report on amelioration
      of quality-of-life surrogates. We also provide an overview on DBS surgery in less
      common dystonic syndromes, such as craniofacial dystonia, status dystonicus, task
      specific dystonia, paroxysmal dystonia, camptocormia, and secondary dystonias,
      including choreoathetosis, hemidystonia, tardive dystonia, and pantothenate
      kinase-associated neurodegeneration. Furthermore, we discuss the implications of
      intra-operative microelectrode recordings and pallidal field potentials for the
      pathophysiology of dystonia and the particular possible mechanisms of DBS in
      dystonia. Finally, future perspectives are outlined.

PMID- 22151219
TI  - Closed-loop control of functional electrical stimulation-assisted arm-free
      standing in individuals with spinal cord injury: a feasibility study.
AB  - Objectives.  The purpose of the present study was to show that the design of a
      neuroprosthesis for unsupported (arm-free) standing is feasible. We review
      findings suggesting that a closed-loop controlled functional electrical
      stimulation (FES) system should be able to facilitate arm-free quiet standing in
      individuals with spinal cord injury (SCI). Particularly, this manuscript
      identifies: 1) a control strategy that accurately mimics the strategy healthy
      individuals apply to regulate the ankle joint position during quiet standing and
      2) the degrees of freedom (DOF) of the redundant, closed-chain dynamic system of
      bipedal stance that have to be regulated to facilitate stable standing. Methods
      and Results.  First, we utilized a single DOF model of quiet standing (inverted
      pendulum) to analytically identify a proportional and derivative (PD) feedback
      controller that regulates the ankle torque in a physiologic manner despite a long
      sensory-motor time delay. Second, these theoretic results were experimentally
      validated by implementing the proposed PD controller to stabilize an individual
      with SCI during quiet standing. Third, a realistic, three-dimensional dynamic
      model of quiet standing with 12 DOF was used to determine the optimal combination
      of the minimum number of DOF that need to be regulated with the PD controller to
      ensure stability during quiet standing. Finally, perturbation simulations
      confirmed that the kinematics of this system are similar to those of healthy
      individuals during perturbed standing. Conclusions.  The presented results
      suggest that stable standing can be achieved in individuals with SCI by
      controlling only six DOF in the lower limbs using FES, and that a PD controller
      actuating these DOF can stabilize the system despite a long sensory-motor time
      delay. Our finding that not all DOF in the lower limbs need to be regulated is
      particularly relevant for individuals with complete SCI, because some of their
      muscles may be denervated or difficult to access.

PMID- 22151220
TI  - Dorsal column stimulation in persistent vegetative state.
AB  - Objectives.  The problem of treating patients in a vegetative state remains
      grossly unresolved, and spinal cord stimulation (SCS) had seemed promising in
      some studies, suggesting, to us, further study. Materials and Methods.  A
      prospective uncontrolled and nonrandomized observational study for 20 consecutive
      years (1986-2005) was performed on the effect of SCS in 214 patients in
      persistent vegetative state (PVS) that resulted from global anoxia and/or, stroke
      and/or head injury. After confirming the condition of PVS, a spinal cord
      stimulator, at the C2-C4 level, was implanted, stimulating according to a
      protocol of 15-min on/15-min off during daytime only. The results were evaluated
      using an efficacy scale designed by us for our study, detecting signs of
      awareness of self and surrounding. Results.  Excellent and positive results were
      obtained in 109 of 201 patients (54%), but better in those patients below the age
      of 35, those of PVS of traumatic origin and those patients with regional cerebral
      blood flow over 20 mL/100 g/min. Conclusions.  These findings, though
      inconclusive of actual benefit of SCS for PVS, indicate to us that further
      evidence-based, randomized controlled trials are needed to confirm efficacy of
      the treatment and define those who are going to benefit from this treatment
      method.

PMID- 22151221
TI  - Effect of temporary spinal cord stimulation on postherpetic neuralgia in the
      thoracic nerve area.
AB  - Objectives.  The pain associated with herpes zoster can be classified as acute
      phase, persistent phase, or chronic phase, but if it is prolonged, it becomes
      resistant to treatment. It is clinically important to prevent transition to
      postherpetic neuralgia after the onset of herpes zoster, and the outcome depends
      on whether continuous and potent pain management can be achieved between the
      acute and persistent phases. We evaluated the effect of pain management leading
      to quick termination of pain using temporary spinal cord stimulation (SCS) which
      does not require implantation of a device. Materials and Methods.  We performed
      continuous epidural blocks (CEB) on 52 patients with severe persistent pain of
      postherpetic neuralgia in the thoracic nerve area, and also inserted spinal
      stimulation leads in 14 who showed no improvement in the severe pain with
      concomitant pharmacotherapy. We expected to see the termination of pain with
      adequate analgesic effects mainly with SCS, and secondarily with the epidural
      analgesia as rescue therapy. Results.  Severe pain accompanied by sensory
      dysfunction remained in 14 cases. By introducing SCS to the CEB, the visual
      analog scale baseline was rapidly reduced. Less epidural analgesia was required
      and the adverse reactions of lowered blood pressure in three cases and urinary
      retention in seven cases disappeared soon. The self-rated satisfaction was higher
      with SCS than with CEB in all 14 cases, because it is highly controllable and has
      minimal activities of daily living-lowering effects. Conclusion.  Temporary SCS,
      which does not require implantation of a device, may have a potent analgesic
      effect on severe pain in patients in the persistent phase after herpes zoster,
      and prevent transition to postherpetic neuralgia.

PMID- 22151222
TI  - Neuromodulation of neuropathic pain syndrome induced by elapidae (cobra)
      envenomation.
AB  - Objectives.  This study aims to demonstrate the utility of spinal cord
      stimulation in a neuropathic pain syndrome and overall decline in health and
      functional independence following elapid envenomation in a morbidly obese,
      insulin-dependent diabetic. Materials and Methods.  A two-lead, 16-electrode
      constant-current, independently controlled system is placed in the mid-cervical
      spine. Results.  Noted were a improvement in overall health status with better
      glycemic control and return to work status in response to adequate pain control.
      Conclusions.  The case serves as a model for other orphan pain cases with a
      seemingly esoteric etiology and adds to the existing body of literature that
      spinal cord stimulation and neuromodulation, in general, has a wide-ranging
      applicability peripheral neuropathic pain syndromes.

PMID- 22151223
TI  - A Cadaveric and in vitro Controlled Comparative Investigation of Percutaneous
      Spinal Cord Lead Anchoring.
AB  - Spinal cord stimulator lead migration is a common problem. Anchor design may be a
      factor in its prevention. We have undertaken a cadaveric and in vitro comparative
      investigation of the force required to cause lead migration with a variety of
      anchor types. Thirty-eight spinal cord stimulator leads were anchored with short
      silastic (N = 8), long silastic (N = 16) and titanium (N = 10) devices in
      cadavers. Twenty-eight further spinal cord stimulator lead anchorings were
      undertaken on the bench with the titanium anchor and three different octrode
      leads. The median force to cause lead movement in cadavers was 0.55 Newtons (N)
      for short silastic anchors, 0.81 N and 0.63 N for two types of long silastic
      anchor, and 1.3 N for the titanium anchor. There was a significant difference
      between long and short silastic anchors (p < 0.01) and a significant difference
      between the titanium anchor and the silastic anchors (p < 0.003). There was an
      insignificant difference in the force required to cause lead movement repeated by
      the same operator (p = 0.36). There was no significant difference between
      inexperienced and experienced operators (p = 0.88). There was no significant
      difference between the different leads using the titanium anchor (p = 0.06). The
      titanium anchor prevents simulated lead movement at greater forces that the
      silastic anchors with a variety of leads. For silastic anchors, movement occurred
      at median force below that simulated with spinal movement; for the titanium
      anchor, movement occurred at a median force above that simulated with spinal
      movement. Further in vivo investigations are warranted to assess the potential of
      titanium anchoring to significantly reduce spinal cord stimulator lead migration.

PMID- 22151224
TI  - Spinal cord stimulation for pain management in ankylosing spondylitis: a case
      report.
AB  - Introduction.  The classic presentation of ankylosing spondylitis not only
      impairs spinal mobility but also imposes functional limitations, and fatigue is
      common. Methods.  We report here the outcomes of spinal cord stimulation (SCS) in
      the case of a 47-year-old man with low back and hip/thigh pain due to ankylosing
      spondylitis, with failed responses to conservative therapies aimed at treating
      this pain. Results.  Spinal cord stimulation induced axial low back and bilateral
      hip paresthesia resulting in complete subjective pain relief, cessation of
      analgesic medications, reduced fatigue, and improved sleep patterns. SCS also
      resulted in improved socioeconomic outcomes with a return to work. Conclusions. 
      With further research in patients with broader presentations of the disease, SCS
      may prove efficacious in suppressing intractable pain symptoms due to ankylosing
      spondylitis, thus improving quality of life measures.

PMID- 22151225
TI  - Peripheral nerve field stimulation: is age an indicator of outcome?
AB  - Objective.  This study aims to assess peripheral nerve field stimulation as a
      treatment option for chronic pain and test for indicators of outcome. Materials
      and Methods.  We reviewed all patients permanently implanted with peripheral
      nerve field stimulators over the past 24 months. A questionnaire was used to
      assess outcomes. Results.  Twenty-seven questionnaires were sent out and 23/27
      responded. A significant average decrease of 4.02 visual analog scale points was
      observed. The average pain decrease for the low back was 3.77 points and 5.9 for
      occipital implants. An age effect was detected; younger patients (<60 years)
      reported an average pain relief of 4.79 points while older patients (>61 years)
      reported an average pain relief decrement of only 2.83 points. Most patients
      reported decreases in analgesic use after treatment. Pain relief was
      significantly and highly correlated with reduced analgesic intake and patient
      satisfaction. Conclusion.  Peripheral nerve field stimulation is a safe,
      reversible, and effective treatment option for patients with chronic pain,
      particularly those under 60 years.

PMID- 22151226
TI  - Peripheral nerve stimulation: a treatment for chronic low back pain and failed
      back surgery syndrome?
AB  - Objective.  This study aims to evaluate the usefulness of peripheral nerve
      stimulation as a treatment option for patients with chronic low back pain.
      Materials and Methods.  More than 12 months, we collected data on consecutive
      patients who had successful trials and were subsequently implanted with octrode
      percutaneous leads placed subcutaneously within the major area of pain. Eleven
      patients met diagnostic criteria for failed back surgery syndrome. A
      questionnaire assessed outcomes including: pain, analgesic use, and patient
      satisfaction. The response rate was 93% (13/14): average follow-up time was seven
      months. Results.  There was a significant decrease in pain levels: an average
      reduction of 3.77 visual analog scale points. Eleven patients (85%) reported
      successful outcomes and an average pain reduction of 4.18 points but two reported
      a poor response. Pain relief was highly correlated with reduced analgesia and
      patient satisfaction. No complications were reported. Conclusion.  This study
      demonstrates a treatment option that is safe, nonpharmacologic, reversible, and
      effective for patients with chronic low back pain that have exhausted other
      treatment options.

PMID- 22151227
TI  - How many neurons do you have? Some dogmas of quantitative neuroscience under
      revision.
AB  - Owing to methodological shortcomings and a certain conservatism that consolidates
      wrong assumptions in the literature, some dogmas have become established and
      reproduced in papers and textbooks, derived from quantitative features of the
      brain. The first dogma states that the cerebral cortex is the pinnacle of brain
      evolution - based on the observations that its volume is greater in more
      'intelligent' species, and that cortical surface area grows more than any other
      brain region, to reach the largest proportion in higher primates and humans. The
      second dogma claims that the human brain contains 100 billion neurons, plus 10
      fold more glial cells. These round numbers have become widely adopted, although
      data provided by different authors have led to a broad range of 75-125 billion
      neurons in the whole brain. The third dogma derives from the second, and states
      that our brain is structurally special, an outlier as compared with other
      primates. Being so large and convoluted, it is a special construct of nature,
      unrelated to evolutionary scaling. Finally, the fourth dogma appeared as a
      tentative explanation for the considerable growth of the brain throughout
      development and evolution - being modular in structure, the brain (and
      particularly the cerebral cortex) grows by tangential addition of modules that
      are uniform in neuronal composition. In this review, we sought to examine and
      challenge these four dogmas, and propose other interpretations or simply their
      replacement with alternative views.

PMID- 22151228
TI  - Moving between rooms--moving between life and death: nurses' experiences of
      caring for terminally ill patients in hospitals.
AB  - AIM: This study describes the meanings of generalist registered nurses'
      experiences of caring for palliative care patients on general wards in hospitals.
      BACKGROUND: Earlier research shows that work with patients in palliative care is
      demanding. More research concerning palliative care is undertaken in oncological
      care, in hospice and in home-care settings than in general wards. It is therefore
      important to examine the palliative care in the context of acute-care settings to
      discover more about this phenomenon, to understand the experiences of nurses in
      this situation and to develop patient care. DESIGN: Qualitative, descriptive and
      interpretive study. METHOD: Eight registered nurses in two different hospitals in
      Sweden were interviewed. The patients on these wards suffered from surgical and
      medical conditions, i.e. both curative and palliative care were administered. The
      interviews were analysed using a phenomenological hermeneutical approach inspired
      by Ricoeur's philosophy. RESULTS: The registered nurses' experiences are
      presented as seven themes and a comprehensive, interpreted whole. This latter
      revealed the significance of contrasts, contradictions and movement between the
      material and psychological experiences of the room and nursing care in this care
      context. CONCLUSIONS: The registered nurses say that something momentous occurred
      during the care process and they showed a strong determination and commitment to
      being part of the ending of the patient's life circle, despite the situation
      often being one of stress. RELEVANCE TO CLINICAL PRACTICE: The findings highlight
      the need for various forms of support for the nurses to meet their need for new
      and updated knowledge and support in existential matters. This may promote a
      better quality of care and confirm the nurses in their caring practice. Moreover,
      there is a need to introduce the hospice philosophy into acute-care settings in
      hospitals.

PMID- 22151229
TI  - Inflammation and cancer: a comparative view.
AB  - Rudolph Virchow first speculated on a relationship between inflammation and
      cancer more than 150 years ago. Subsequently, chronic inflammation and associated
      reactive free radical overload and some types of bacterial, viral, and parasite
      infections that cause inflammation were recognized as important risk factors for
      cancer development and account for one in four of all human cancers worldwide.
      Even viruses that do not directly cause inflammation can cause cancer when they
      act in conjunction with proinflammatory cofactors or when they initiate or
      promote cancer via the same signaling pathways utilized in inflammation. Whatever
      its origin, inflammation in the tumor microenvironment has many cancer-promoting
      effects and aids in the proliferation and survival of malignant cells and
      promotes angiogenesis and metastasis. Mediators of inflammation such as
      cytokines, free radicals, prostaglandins, and growth factors can induce DNA
      damage in tumor suppressor genes and post-translational modifications of proteins
      involved in essential cellular processes including apoptosis, DNA repair, and
      cell cycle checkpoints that can lead to initiation and progression of cancer.

PMID- 22151230
TI  - Metabolic glycoengineering through the mammalian GalNAc salvage pathway.
AB  - GalNAc is the initial sugar of mucin-type O-glycans, and is a component of
      several tumor antigens. The aim of this work was to determine whether synthetic
      GalNAc analogs could be taken up from the medium and incorporated into complex
      cellular O-glycans. The cell line employed was CHO ldlD, which can only use
      GalNAc and Gal present in the medium for the synthesis of its glycans. All GalNAc
      analogs with modified N-acyl groups (N-formyl, N-propionyl, N-glycolyl, N
      azidoacetyl, N-bromoacetyl, and N-chloroacetyl) were incorporated into cellular O
      glycans, although to different extents. The GalNAc analogs linked to Ser or Thr
      could be extended by the beta3-galactosyltransferase glycoprotein-N
      acetylgalactosamine 3beta-galactosyl transferase 1 in vitro and in vivo and by
      alpha6-sialyltransferase alpha-N-acetylgalactosaminide-alpha-2,6
      sialyltransferase 1. At the surface of CHO ldlD cells, all analogs were
      incorporated into sialylated O-glycan structures like those present on wild-type
      CHO cells, indicating that the GalNAc analogs do not change the overall structure
      of core-1 O-glycans. In addition, this study shows that the unnatural synthetic
      GalNAc analogs can be incorporated into human tumor cells, and that a tumor
      antigen modified by an analog can be readily detected by a specific antiserum.
      GalNAc analogs are therefore potential targets for tumor immunotherapy.

PMID- 22151231
TI  - Genomic distance under gene substitutions.
AB  - BACKGROUND: The distance between two genomes is often computed by comparing only
      the common markers between them. Some approaches are also able to deal with non
      common markers, allowing the insertion or the deletion of such markers. In these
      models, a deletion and a subsequent insertion that occur at the same position of
      the genome count for two sorting steps. RESULTS: Here we propose a new model that
      sorts non-common markers with substitutions, which are more powerful operations
      that comprehend insertions and deletions. A deletion and an insertion that occur
      at the same position of the genome can be modeled as a substitution, counting for
      a single sorting step. CONCLUSIONS: Comparing genomes with unequal content, but
      without duplicated markers, we give a linear time algorithm to compute the
      genomic distance considering substitutions and double-cut-and-join (DCJ)
      operations. This model provides a parsimonious genomic distance to handle genomes
      free of duplicated markers, that is in practice a lower bound to the real genomic
      distances. The method could also be used to refine orthology assignments, since
      in some cases a substitution could actually correspond to an unannotated
      orthology.

PMID- 22151232
TI  - Abstracts of the Royal College of Radiologists Breast Group Annual Scientific
      Meeting 2011. Glasgow, United Kingdom. November 7-8, 2011.

PMID- 22151233
TI  - The assessment of the quality of reporting of meta-analyses in diagnostic
      research: a systematic review.
AB  - BACKGROUND: Over the last decade there have been a number of guidelines
      published, aimed at improving the quality of reporting in published studies and
      reviews. In systematic reviews this may be measured by their compliance with the
      PRISMA statement. This review aims to evaluate the quality of reporting in
      published meta-analyses of diagnostic tests, using the PRISMA statement and
      establish whether there has been a measurable improvement over time. METHODS:
      Eight databases were searched for reviews published prior to 31(st) December
      2008. Studies were selected if they evaluated a diagnostic test, measured
      performance, searched two or more databases, stated the search terms and
      inclusion criteria, and used a statistical method to summarise a test's
      performance. Data were extracted on the review characteristics and items of the
      PRISMA statement. To measure the change in the quality of reporting over time,
      PRISMA items for two periods of equal duration were compared. RESULTS: Compliance
      with the PRISMA statement was generally poor: none of the reviews completely
      adhered to all 27 checklist items. Of the 236 meta-analyses included following
      selection: only 2(1%) reported the study protocol; 59(25%) reported the searches
      used; 76(32%) reported the results of a risk of bias assessment; and 82(35%)
      reported the abstract as a structured summary. Only 11 studies were published
      before 2000. Thus, the impact of QUOROM on the quality of reporting was not
      evaluated. However, the periods 2001-2004 and 2005-2008 (covering 93% of studies)
      were compared using relative risks (RR). There was an increase in the proportion
      of reviews reporting on five PRISMA items: eligibility criteria (RR 1.13, 95% CI
      1.00 - 1.27); risk of bias across studies (methods) (RR 1.81, 95% CI 1.34 -
      2.44); study selection results (RR 1.48, 95% CI 1.05 - 2.09); results of
      individual studies (RR 1.37, 95% CI 1.09 - 1.72); risk of bias across studies
      (results) (RR 1.65, 95% CI 1.20 - 2.25). CONCLUSION: Although there has been an
      improvement in the quality of meta-analyses in diagnostic research, there are
      still many deficiencies in the reporting which future reviewers need to address
      if readers are to trust the validity of the reported findings.

PMID- 22151234
TI  - Third-party mesenchymal stromal cell infusion is associated with a decrease in
      thrombotic microangiopathy symptoms observed post-hematopoietic stem cell
      transplantation.
AB  - TA-TMA is a pathology that occurs after allogenic HSC transplantation with an
      incidence of 4-13%, and represents one of the most severe vascular damage related
      with this therapy. We report here the case of a nine-yr-old girl suffering from a
      severe refractory aplastic anemia who received an unrelated, 9/10 HLA-matched
      HSC. Soon after transplantation, the patient developed a graft-versus-host
      disease (GvHD), a TA-TMA, and renal insufficiency. These pathologies remained
      refractory to the various treatments undertaken and required several
      hospitalizations in the intensive care unit. On day 106 post-HSC transfusion,
      after several episodes of intensive care, the patient was infused with
      mismatched, third-party MSCs. Schizocyte levels rapidly decreased after MSC
      infusion, and two wk later, most biological parameters returned to normal.
      Erythrocyte and thrombocyte transfusions were discontinued, and the patient
      remained stable for 10 wk. Thereafter, TA-TMA symptoms, viral reactivation,
      pleural and cardiac effusions reappeared and lead to the death of the patient.
      Our observations suggest that allogenic MSC infusion may decrease the symptoms of
      TA-TMA, but further investigation is required to determine how and when MSC
      should be infused to develop a long-lasting protective effect.

PMID- 22151235
TI  - Plasma secretory phospholipase A2-IIa as a potential biomarker for lung cancer in
      patients with solitary pulmonary nodules.
AB  - BACKGROUND: Five-year survival for lung cancer has remained at 16% over last
      several decades largely due to the fact that over 50% of patients are diagnosed
      with locally-advanced or metastatic disease. Diagnosis at an earlier and
      potentially curable stage is crucial. Solitary pulmonary nodules (SPNs) are
      common, but the difficulty lies in the determination of which SPN is malignant.
      Currently, there is no convenient and reliable biomarker effective for early
      diagnosis. Secretory phospholipase A2-IIa (sPLA2-IIa) is secreted into the
      circulation by cancer cells and may allow for an early detection of lung cancer.
      METHODS: Plasma samples from healthy donors, patients with only benign SPN, and
      patients with lung cancer were analyzed. Expression of sPLA2-IIa protein in lung
      cancer tissues was also determined. RESULTS: We found that the levels of plasma
      sPLA2-IIa were significantly elevated in lung cancer patients. The receiver
      operating characteristic curve analysis, comparing lung cancer patients to
      patients with benign nodules, revealed an optimum cutoff value for plasma sPLA2
      IIa of 2.4 ng/ml to predict an early stage cancer with 48% sensitivity and 86%
      specificity and up to 67% sensitivity for T2 stage lung cancer. Combined sPLA2
      IIa, CEA, and Cyfra21.1 tests increased the sensitivity for lung cancer
      prediction. High level of plasma sPLA2-IIa was associated with a decreased
      overall cancer survival. sPLA2-IIa was overexpressed in almost all non-small cell
      lung cancer and in the majority of small cell lung cancer by immunohistochemistry
      analysis. CONCLUSION: Our finding strongly suggests that plasma sPLA2-IIa is a
      potential lung biomarker to distinguish benign nodules from lung cancer and to
      aid lung cancer diagnosis in patients with SPNs.

PMID- 22151237
TI  - The Great Eastern Japan Earthquake and psychogeriatric services.

PMID- 22151236
TI  - Donor-specific indirect pathway analysis reveals a B-cell-independent signature
      which reflects outcomes in kidney transplant recipients.
AB  - To investigate the role of donor-specific indirect pathway T cells in renal
      transplant tolerance, we analyzed responses in peripheral blood of 45 patients
      using the trans-vivo delayed-type hypersensitivity assay. Subjects were enrolled
      into five groups-identical twin, clinically tolerant (TOL), steroid monotherapy
      (MONO), standard immunosuppression (SI) and chronic rejection (CR)-based on
      transplant type, posttransplant immunosuppression and graft function. The
      indirect pathway was active in all groups except twins but distinct intergroup
      differences were evident, corresponding to clinical status. The antidonor
      indirect pathway T effector response increased across patient groups (TOL < MONO
      < SI < CR; p < 0.0001) whereas antidonor indirect pathway T regulatory response
      decreased (TOL > MONO = SI > CR; p < 0.005). This pattern differed from that seen
      in circulating naive B-cell numbers and in a cross-platform biomarker analysis,
      where patients on monotherapy were not ranked closest to TOL patients, but rather
      were indistinguishable from chronically rejecting patients. Cross-sectional
      analysis of the indirect pathway revealed a spectrum in T-regulatory:T-effector
      balance, ranging from TOL patients having predominantly regulatory responses to
      CR patients having predominantly effector responses. Therefore, the indirect
      pathway measurements reflect a distinct aspect of tolerance from the recently
      reported elevation of circulating naive B cells, which was apparent only in
      recipients off immunosuppression.

PMID- 22151238
TI  - Specific feature of olfactory dysfunction with Alzheimer's disease inspected by
      the Odor Stick Identification Test.
AB  - AIM: Alzheimer's disease (AD) is one of the most significant diseases associated
      with ageing. As the disease progresses, symptoms including olfactory dysfunction
      often appear along with cognitive dysfunction. We examined olfactory and other
      indexes to investigate correlations between them and the validity of an olfactory
      test for screening for AD. METHODS: To assess whether odorant identification will
      be a useful diagnostic tool, we investigated the olfactory ability of Alzheimer's
      disease patients (ADs) using the Odor Stick Identification Test for the Japanese.
      As a control, we compared ADs to aged people without AD or dementia. To
      investigate the relationship between olfactory loss and severity of AD, we used
      the Mini-Mental State Examination, Alzheimer's Disease Assessment Scale,
      biomarkers in spinal fluid and single-photon emission computed tomography as
      brain imaging. RESULTS: In comparing the controls and ADs, we believe that there
      are significant differences, with ADs having particularly low activity with
      regard to olfactory function and some odorants. We showed that there was a
      definite correlation between cognitive and olfactory function. To confirm this,
      we sorted subjects by markers of severity scores for comparison. In all areas,
      the AD group had more serious olfactory dysfunction, including in the early
      stages of AD. CONCLUSION: This study suggests that olfactory tests such as the
      Odor Stick Identification Test for the Japanese can be useful for assessing
      severity of AD, including cognitive dysfunction. Further investigations will
      enable us to establish an olfactory assessment method for the screening or
      diagnosis of AD.

PMID- 22151239
TI  - A figurative proverb test for dementia: rapid detection of disinhibition, excuse
      and confabulation, causing discommunication.
AB  - BACKGROUND: Communicative disability is regarded as a prominent symptom of
      demented patients, and many studies have been devoted to analyze deficits of
      lexical-semantic operations in demented patients. However, it is often observed
      that even patients with preserved lexical-semantic skills might fail in
      interactive social communication. Whereas social interaction requires pragmatic
      language skills, pragmatic language competencies in demented subjects have not
      been well understood. We propose here a brief stress-free test to detect
      pragmatic language deficits, focusing on non-literal understanding of figurative
      expression. We hypothesized that suppression of the literal interpretation was
      required for figurative language interpretation. METHODS:  We examined 69
      demented subjects, 13 subjects with mild cognitive impairment and 61 healthy
      controls aged 65 years or more. The subjects were asked the meaning of a familiar
      proverb categorized as a figurative expression. The answers were analyzed based
      on five factors, and scored from 0 to 5. To consider the influence of cognitive
      inhibition on proverb comprehension, the scores of the Stroop Colour-Word Test
      were compared concerning correct and incorrect answers for each factor,
      respectively. Furthermore, the characteristics of answers were considered in the
      light of excuse and confabulation qualitatively. RESULTS: The proverb
      comprehension scores gradually decreased significantly as dementia progressed.
      The literal interpretation of the proverb, which showed difficulties in
      figurative language comprehension, was related to disinhibition. The qualitative
      analysis showed that excuse and confabulation increased as the dementia stage
      progressed. CONCLUSIONS: Deficits in cognitive inhibition partly explains the
      difficulties in interactive social communication in dementia. With qualitative
      analysis, asking the meaning of a proverb can be a brief test applied in a
      clinical setting to evaluate the stage of dementia, and to illustrate
      disinhibition, confabulation and excuse, which might cause discommunication and
      psychosocial maladjustment in demented patients.

PMID- 22151240
TI  - Reliability and validity of the Japanese version of the Agitated Behaviour in
      Dementia Scale in Alzheimer's disease: three dimensions of agitated behaviour in
      dementia.
AB  - BACKGROUND: Agitation in dementia seriously affects not only patients' quality of
      life (QOL), but also caregivers' QOL. Thus, an appropriate assessment of agitated
      behaviour in dementia is needed for clinical management. We developed the
      Japanese version of the Agitated Behaviour in Dementia scale (ABID), examined its
      reliability and validity, and carried out its factor analysis to elucidate its
      factor structure. METHODS: The Japanese version of the ABID was given caregivers
      of 149 Japanese patients with Alzheimer's disease (AD). The internal-consistency,
      test-retest reliability and concurrent validity of the Japanese version of the
      ABID were then examined. A factor analysis was used to examine the agitated
      behavioural dimensions underlying ABID. RESULTS: The Japanese version of the ABID
      showed an excellent internal reliability for both frequency ratings (Cronbach's
      alpha= 0.89) and reaction ratings (Cronbach's alpha= 0.92), and an excellent test
      retest reliability for both frequency ratings and reaction ratings. The total
      score for the frequency ratings of the ABID was significantly associated with the
      Cohen-Mansfield Agitation Inventory (CMAI), and the total score for the reaction
      ratings of the ABID was significantly associated with the Zarit Burden Interview.
      The factor analysis showed three subtypes: physically agitated behaviour,
      verbally agitated behaviour and psychosis symptoms. CONCLUSIONS: The Japanese
      version of the ABID promises to be useful for assessing agitated behaviour in
      patients with AD. Importantly, understanding these subtypes of agitated behaviour
      might have implications for individualized treatment plans.

PMID- 22151241
TI  - Yamaguchi fox-pigeon imitation test (YFPIT) for dementia in clinical practice.
AB  - BACKGROUND:  In out-patient clinics, having simple procedures to check for signs
      of dementia is invaluable. In the present study, we evaluated the imitation of
      hand gestures to detect visuomotor deficits in dementia in clinical practice.
      METHODS: In all, 1219 subjects were enrolled in the present study, including 497
      with Alzheimer's disease (AD), 98 with dementia with Lewy bodies (DLB), 71 with
      other types of dementia diseases, 175 with a Clinical Dementia Rating (CDR) of
      0.5, and 378 normal controls. All subjects were aged 65 years or older. Subjects
      were recruited from 10 clinics and two communities. Visuomotor function was
      evaluated by the Yamaguchi fox-pigeon imitation test (YFPIT), which consists of a
      simple one-handed sign for 'fox' and a complex two-handed sign for 'pigeon', a
      rapid, game-like test with low psychological burden. RESULTS: The success rate
      (successful/total) for imitating the 'pigeon' hand gesture was reduced as the
      severity of the dementia increased: 85.7% in normal controls, 60.6% in CDR 0.5
      (mild cognitive impairment), 39.2% in CDR 1 (mild dementia), 21.2% in CDR 2
      (moderate dementia), and 5.7% in CDR 3 (severe dementia). The success rate for
      imitating the 'pigeon' hand gesture was higher in patients with DLB than AD
      within the CDR 1 group (51.2% vs 35.4%, respectively), but lower for patients
      with DLB than AD within the CDR 2 group (12.5% vs 24.4%, respectively). The
      success of imitating the hand gesture for 'fox' was similar for patients with AD
      and DLB. Of those subjects who failed to imitate the hand gesture for 'pigeon',
      49.5% of those with AD showed the palm-palm pattern (both palms facing outward),
      suggesting deficits of perspective conversion from the first-person to the third
      person. Conversely, 52.8% of patients with DLB showed a dorsum-dorsum pattern
      (both dorsa facing outwards), suggesting deterioration of visual attention and
      recognition. CONCLUSION: In conclusion, the YFPIT is a useful test to detect
      visuomotor deficits in dementia that can differentiate between AD and DLB.

PMID- 22151242
TI  - The association of depression and multimorbidity in the elderly: implications for
      the assessment of depression.
AB  - BACKGROUND: Depression and multimorbidity are common in the elderly. Assessing
      depression might be difficult because of the overlap of depressive and somatic
      symptoms, possibly leading to confounded results. METHODS: This study
      investigates the frequency of depression, multimorbidity and their association,
      the potential impact of multimorbidity on the assessment of depression by the
      Patient Health Questionnaire, and whether using a cut point might cause
      misleading results in the elderly German population (60-85 years, n= 1659).
      RESULTS: Depressive syndromes are significantly more frequent in multimorbid
      respondents. Multimorbidity is associated with higher item scores, especially in
      the somatic items, and multimorbid respondents show higher depression severity
      levels in comparison to non-multimorbid persons. CONCLUSION: There are
      associations between multimorbidity and depressive symptoms, therefore
      potentially confounding prevalence rates. As such, causal pathways of these
      associations should be studied under a longitudinal perspective in future
      studies.

PMID- 22151243
TI  - Differentiation between amnestic-mild cognitive impairment and early-stage
      Alzheimer's disease using the Frontal Assessment Battery test.
AB  - BACKGROUND:  Previous research has described the executive dysfunction that
      occurs in patients with amnestic-mild cognitive impairments (A-MCI) and early
      stage Alzheimer's disease (EAD), which are comparatively similar stages of
      dementia. The aim of the present cross-sectional study is to evaluate executive
      dysfunction using the Frontal Assessment Battery (FAB) screening test in two
      groups and to investigate the interaction with other cognitive impairments.
      METHODS: Among 170 consecutive patients with Alzheimer's disease or A-MCI, we
      recruited 48 subjects who were under 75 years of age and had been diagnosed as
      having either A-MCI or EAD. We then compared the total and the subtest scores of
      the mini-mental state examination (MMSE) and the FAB between the two groups.
      Moreover, we investigated the statistical interactive associations of the FAB
      subtest scores with the influential MMSE subtest scores or the diagnosis (A-MCI
      or EAD). RESULTS: No significant differences in the age, sex ratio, duration of
      illness, and education years were observed between the two groups. However,
      significant differences in the FAB total and subtest scores (conflicting
      instructions and go/no-go) were found between the two groups. Furthermore,
      significant differences in the MMSE total and subtest scores (orientation, memory
      delayed recall, and attention and calculation) were also noted between the two
      groups. In a generalized linear model analysis, only two FAB subtest scores
      (conflicting instructions and go/no-go) were significantly influenced by the
      diagnosis (A-MCI or EAD) in a manner that was independent of the interaction with
      the orientation or memory delayed recall. CONCLUSION: The present findings
      suggest that the FAB total score and subtest scores reflecting interference
      performances (conflicting instructions and go/no-go) significantly declined in
      patients with EAD, independent of the disorientation and memory disorder. Such
      characteristics of neuropsychological screening test scores may be useful to
      clinicians for differentiating EAD and A-MCI at bedside.

PMID- 22151244
TI  - Biting for attention: a case of dental discomfort manifesting in behavioural
      problems.
AB  - There is a dearth of literature describing behaviour that expresses discomfort
      caused by poor dentition in patients with dementia. In this paper, we report on a
      patient whose behaviour only abstrusely pointed to his teeth as the source of
      discomfort. Although changes to his medication over a 2-year period had little
      effect, eventual extraction of his caries brought about an almost immediate
      resolution of all antisocial behaviour. Clinicians must be mindful that poor
      dental care is easily meliorated but remains endemic in patients suffering from
      dementia.

PMID- 22151245
TI  - Recurrent cholecystitis in an elderly mentally retarded patient with pica.
AB  - The case of a 64-year-old patient with pica and severe mental retardation who was
      admitted to our hospital for treatment of recurrent cholecystitis is reported.
      Abdominal ultrasound showed sludge in the gallbladder, but no stones. Abdominal
      CT revealed a foreign body in the duodenum resembling a suction cup of the type
      commonly used in kitchens and bathrooms. The object could not be removed because
      it was deeply embedded in the hypertrophic intestinal mucosa. A nasogastric tube
      was inserted for feeding, since the object impeded the passage of solid foods.
      The patient's fever and abdominal pain subsequently resolved, and laboratory data
      improved. The indwelling feeding tube prevented recurrence of cholecystitis.
      Since pica is common not only in patients with mental retardation but also in
      dementia patients, the present case may also relate to the treatment of acute
      abdominal conditions in dementia patients.

PMID- 22151246
TI  - Depressive state, aging, and prevalence of snacking: a preliminary study.

PMID- 22151247
TI  - Knockdown of MYB305 disrupts nectary starch metabolism and floral nectar
      production.
AB  - MYB transcription factors have important roles during floral organ development.
      In this study, we generated myb305 RNAi knockdown tobacco plants and studied the
      role of MYB305 in the growth of the floral nectary. We have previously shown the
      MYB305 regulates the expression of flavonoid metabolic genes as well as of nectar
      proteins (nectarins); however, the myb305 plants showed other floral phenotypes
      that we investigate in these studies. The nectaries of myb305 plants show
      juvenile character at late stages of development and secrete reduced levels of
      nectar. Because starch metabolism is intimately involved in nectar secretion and
      is strongly regulated during normal nectary development, we examined the
      accumulation of starch in the nectaries of the myb305 plants. The myb305 plants
      accumulated lower levels of starch in their nectaries than did wild-type plants.
      The reduced starch correlated with the reduced expression of the ATP-glucose
      pyrophosphorylase (small subunit) gene in nectaries of the myb305 plants during
      the starch biosynthetic phase. Expression of genes encoding several starch
      degrading enzymes including beta-amylase, isoamylase 3, and alpha-amylase was
      also reduced in the myb305 plants. In addition to regulating nectarin and
      flavonoid metabolic gene expression, these results suggest that MYB305 may also
      function in the tobacco nectary maturation program by controlling the expression
      of starch metabolic genes.

PMID- 22151248
TI  - Examination of the communication interface between students with severe to
      profound and multiple intellectual disability and educational staff during
      structured teaching sessions.
AB  - BACKGROUND: Individuals with severe to profound and multiple intellectual
      disability (S-PMID) tend to function at the earlier stages of communication
      development. Variable and highly individual means of communicating may present
      challenges to the adults providing support in everyday life. The current study
      aimed to examine the communication interface between students with S-PMID and
      educational staff. METHOD: An in-depth, observational study of dyadic interaction
      in a class within the secondary part of a special school was conducted. The
      designated educational level was Key Stage 3 under the National Curriculum of
      England, which is typically for children from age 11 to 14 years attending a
      state school. There were four student-teacher dyads in the class. The students
      had multiple impairments with severely limited communication skills. Video
      capture of dyadic interaction was conducted during five English lessons and
      sampled to 2.5 min per dyad per lesson. The video footage was transcribed into
      standard orthography, detailing the vocal and non-vocal aspects. A coding
      framework guided by the principles of structural-functional linguistics was used
      to determine the nature of dyadic interaction, comprising linguistic moves,
      functions and communicative modalities. The relative contributions of student and
      teacher to the interaction were examined. RESULTS: Significant differences were
      found between the students and educational staff on the majority of the measures.
      The teachers dominated the interaction, occupying significantly more turns than
      the students. Teacher turns contained significantly more initiations and follow
      up moves than the students, who used more response moves. Teacher communication
      mainly served the functions of requesting and information giving. Feedback and
      scripted functions were also significantly greater among teacher turns, with only
      limited occurrence among the students. Self- or shared-expression was greatest
      among the students. The modalities of speech, touch, singing and objects were
      used by the teachers for the purpose of communication, whereas vocalisation and
      gesture were used by the students. CONCLUSIONS: Despite differences in the
      availability of communication skills, both student and teacher were able to make
      their respective contributions to the interaction during classroom activity.
      Features of the student-teacher interface retained critical features seen in
      studies of more able individuals with intellectual disability. Scaffolding
      provided by teachers appears to be relevant to the communicative contributions of
      individuals functioning at the earliest stages of communication. The coding
      framework based on structural-functional linguistics provides some new potential
      for examining and enhancing the communication interface between individuals with
      S-PMID and the people who support them.

PMID- 22151249
TI  - Factor X deficiency and pregnancy: preconception counselling and therapeutic
      options.
AB  - Women with factor X deficiency (FXD) who want to become pregnant face uncertain
      risks to themselves and to an unborn infant from haemorrhagic complications
      during pregnancy and at parturition. Women with FXD may also experience
      difficulty achieving pregnancy secondary to haemorrhagic symptoms of the
      reproductive organs. Case reports describe differences in bleeding phenotypes and
      pregnancy outcomes that are not easily correlated with prepregnancy bleeding
      symptoms or factor X levels. The aim of this article is to identify factors for
      consideration and information to assist the physician in counselling women with
      FXD who want to become pregnant, and to offer guidelines for management where
      appropriate. We identified cases of pregnancy among women with FXD and their
      outcomes from the literature; 15 women with 24 pregnancies were identified and 18
      were successful. The women in this small cohort did not have an increased rate of
      spontaneous abortion, (8.3% vs. 13.5% in the general US population) but did have
      a 2.5-fold increased risk of preterm labour (37.5% vs. 12.2% in the general US
      population). The role of prophylaxis to control reproductive haemorrhagic
      symptoms, including haemorrhagic complications of pregnancy has not yet been
      defined, but use of prophylaxis may allow more women to be able to attempt
      pregnancy. Women who had access to a tertiary care centre with a
      multidisciplinary team including an obstetrician with high-risk obstetric
      training, a haematologist, a perinatologist, and access to a reference laboratory
      and blood bank were able in most cases to successfully deliver healthy, term
      infants.

PMID- 22151250
TI  - Canine corneal fibroblast and myofibroblast transduction with AAV5.
AB  - OBJECTIVE: The aims of this study were (1) to determine the efficacy of adeno
      associated vector serotype 5 (AAV5) for delivering gene therapy to canine corneal
      fibroblasts (CCFs) and myofibroblasts (CCMs) using enhanced green fluorescent
      protein (GFP) marker gene and (2) to evaluate the cytotoxicity of AAV5 to CCFs
      and CCMs using an in vitro model. METHODS: Healthy donor canine corneas were used
      to generate primary CCFs by growing cultures in minimal essential medium
      supplemented with 10% fetal bovine serum. Canine corneal myofibroblasts were
      produced by growing cultures in serum-free medium containing transforming growth
      factor beta1 (1 ng/mL). An AAV5 titer (6.5 * 10(12) MUg/mL) expressing GFP under
      control of hybrid cytomegalovirus + chicken beta-actin promoters (AAV5-gfp) was
      used to transduce CCF and CCM cultures. Delivered gene expression in CCFs and
      CCMs was quantified using immunocytochemistry, fluorescent microscopy, and real
      time PCR. Transduction efficacy of the AAV5 vector was determined by counting
      DAPI-stained nuclei and EGFP-positive cells in culture. Phase-contrast
      microscopy, trypan blue, and dUTP nick end labeling (TUNEL) assays were used to
      determine the toxicity and safety of AAV5 in this canine corneal model. RESULTS:
      Topical AAV5 application successfully transduced a significant population of CCFs
      (42.8%; P < 0.01) and CCMs (28%; P < 0.01). Tested AAV5 did not affect CCF or CCM
      phenotype or cellular viability and did not cause significant cell death.
      CONCLUSIONS: The tested AAV5 is an effective and safe vector for canine corneal
      gene therapy in this in vitro model. In vivo studies are warranted.

PMID- 22151251
TI  - Will introducing the new World Health Organization growth reference to Australia
      reduce breastfeeding rates: why not a randomised controlled trial first?
AB  - AIM: The aim is to review the implications of the introduction of new World
      Health Organisation (WHO) growth reference into Australia, and in particular its
      potential effects on breastfeeding rates in the first six months of life.
      METHODS: A review of the velocity and trajectory of growth in the new WHO Growth
      Reference compared to the growth references most commonly used in Australia.
      RESULTS: The World Health Organisation has recommended the universal use of its
      new growth reference. However, in the first 6 months of life, the critical period
      for the maintenance of breastfeeding, the new WHO reference is heavier than the
      reference previously used in Australia. This may mean that more infants will be
      classified as having poor growth. It is likely that these infants will be given
      additional feeds or even may cease being breastfed. Maintenance of breastfeeding
      is important for minimising short-, medium- and long-term risks. CONCLUSIONS:
      Before the introduction of a new growth reference is contemplated, a randomised
      controlled trial should be conducted to be sure that there will be no adverse
      effect on breastfeeding.

PMID- 22151252
TI  - Classifying protein-protein interaction articles using word and syntactic
      features.
AB  - BACKGROUND: Identifying protein-protein interactions (PPIs) from literature is an
      important step in mining the function of individual proteins as well as their
      biological network. Since it is known that PPIs have distinctive patterns in
      text, machine learning approaches have been successfully applied to mine these
      patterns. However, the complex nature of PPI description makes the extraction
      process difficult. RESULTS: Our approach utilizes both word and syntactic
      features to effectively capture PPI patterns from biomedical literature. The
      proposed method automatically identifies gene names by a Priority Model, then
      extracts grammar relations using a dependency parser. A large margin classifier
      with Huber loss function learns from the extracted features, and unknown articles
      are predicted using this data-driven model. For the BioCreative III ACT
      evaluation, our official runs were ranked in top positions by obtaining maximum
      89.15% accuracy, 61.42% F1 score, 0.55306 MCC score, and 67.98% AUC iP/R score.
      CONCLUSIONS: Even though problems still remain, utilizing syntactic information
      for article-level filtering helps improve PPI ranking performance. The proposed
      system is a revision of previously developed algorithms in our group for the ACT
      evaluation. Our approach is valuable in showing how to use grammatical relations
      for PPI article filtering, in particular, with a limited training corpus. While
      current performance is far from satisfactory as an annotation tool, it is already
      useful for a PPI article search engine since users are mainly focused on highly
      ranked results.

PMID- 22151253
TI  - Isolation and characterization of a novel biomineral stalk-forming iron-oxidizing
      bacterium from a circumneutral groundwater seep.
AB  - The Fe-depositing microorganism Gallionella ferruginea was first described in
      1836 based on its association with Fe-rich environments and its distinctive
      morphology. Since then, this morphology has been widely used to identify G.
      ferruginea. Researchers have isolated several Fe-oxidizing bacteria (FeOB)
      related to Gallionella; however, few isolates have produced organized
      extracellular biomineral structures, and of these, only one stalk former has a
      sequenced 16S rRNA gene, listed as G. ferruginea in the GenBank database. Here we
      report the isolation and characterization of a novel stalk-forming Fe-oxidizing
      bacterium, strain R-1, from a freshwater Fe seep. Despite a strong morphological
      similarity to G. ferruginea, this isolate has only 93.55% 16S rRNA gene sequence
      similarity with the previously determined sequence. R-1 only grows on Fe(II)
      substrates, at pH 5.6 to 7.0 and from 10 degrees C to 35 degrees C, with a
      doubling time of ~15 h at pH 6.3 and 22 degrees C. It is a Betaproteobacterium,
      most closely related to uncultured bacteria from microaerobic Fe(II)-rich
      groundwater springs. The most closely related isolates are Sideroxydans spp.
      (94.05-94.42% sequence similarity), FeOB that are not known to produce
      morphologically distinct minerals. To our knowledge, this is the first reported
      stalk-forming freshwater FeOB isolate distinct from Gallionella.

PMID- 22151255
TI  - The need for disclosure.

PMID- 22151254
TI  - Genetic variants in potassium channels are associated with type 2 diabetes in a
      Mongolian population.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS) have identified more
      than 40 common sequence variants associated with type 2 diabetes (T2D). However,
      the results are not always the same in populations with differing genetic
      backgrounds. In the present study, we evaluated a hypothesis that a North Asian
      population living in a geographic area with unusually harsh environmental
      conditions would develop unique genetic risks. METHODS: A population-based
      association study was performed with 21 single-nucleotide polymorphisms (SNPs) in
      nine genes selected according to the results of GWAS conducted in other
      populations. The study participants included 393 full-heritage Mongolian
      individuals (177 diagnosed with T2D and 216 matched controls). Genotyping was
      performed by TaqMan methodology. RESULTS: The strongest association was detected
      with SNPs located within the potassium channel-coding genes KCNQ1 (highest odds
      ratio [OR] = 1.92; P = 3.4 * 10(-5) ) and ABCC8 (OR = 1.79; P = 5 * 10(-4) ).
      Genetic variants identified as strongly influencing the risk of T2D in other
      populations (e.g. KCNJ11 or TCF7L2) did not show significant association in
      Mongolia. CONCLUSIONS:   The strongest T2D risk-associated SNPs in Mongolians are
      located within two of three tested potassium channel-coding genes. Accumulated
      variations in these genes may be related to the exposure to harsh environmental
      conditions.

PMID- 22151256
TI  - Preclinical toxicity study of intrathecal administration of the pain relievers
      dextrorphan, dextromethorphan, and memantine in the sheep model.
AB  - Objectives To determine the toxicity window for the continuous intrathecal
      administration of dextrorphan, dextromethorphan, and memantine via an implanted
      delivery pump. Materials and Methods Using 48 sheep with programmable continuous
      intrathecal infusion systems we determined the behavioral, motor, neurological,
      and histopathological changes produced by a 43-day continuous infusion study of
      dextrorphan, dextromethorphan, and memantine dissolved in 0.9% NaCl. Daily doses
      of each N-methyl-D-aspartate (NMDA) antagonist were 0.013, 0.051, 0.203, 0.510,
      0.811, and 2.533 mg/kg/day, flow rates ranged from 13.25 ml/day to 0.051 ml/day
      at a concentration of 10 mg/ml. Control animals received saline in the range of
      7.9985 ml/day to 1 ml/day. Conclusions Infusion of saline in the control animals
      produced no behavioral or motor changes. However, infusion of dextrorphan,
      dextromethorphan, and memantine at the higher doses (> 0.051 mg/kg/day) produced
      dose-dependent negative behavioral, motor, and histopathologic changes as
      indicated by a series of nonparametric statistical analyses. The minimal toxic
      doses were dextrorphan dose 3, dextromethorphan dose 1 and memantine dose 1. This
      study suggests that continuous intrathecal infusion of dextrorphan,
      dextromethorphan, and memantine via an implantable pump system can cause
      significant toxicities at the higher doses studied.

PMID- 22151257
TI  - The effects of long-term intraspinal infusion therapy with noncancer pain
      patients: evaluation of patient, significant-other, and clinic staff appraisals.
AB  - Objective. This study examines, in a retrospective fashion, the effects of
      intraspinal infusion therapy, primarily using opioids, in the treatment of
      recalcitrant noncancer pain in a sample of 29 consecutive patients. Patients
      were, on average, 58 years of age having had one surgery, with a pain duration of
      221 months. Mean follow-up duration was 31 months. Telephone interviews by a
      disinterested party were used to obtain follow-up data from patients and their
      significant others. In addition, clinic staff rated patient improvement. Results.
      The patients reported an average of 63.4% improvement in pain; 45.5% improvement
      in activity level; and a 53.8% improvement in "ease" of performing activities.
      Average pain level on a numerical rating scale decreased from 8.91/10 to 5.03/10.
      The number of patients reporting a pain level of 5/10 or less increased from 1/29
      to 15/29. Patients generally reported long-term benefit to be equal to or greater
      than that realized during the intrathecal trial. Approximately 86% of patients
      reported a "good" or "excellent" outcome. Significant-other ratings of
      improvement correlated more highly with clinic staff than with patients. No
      statistically significant differences were observed when worker's compensation
      (WC) patients were compared with nonworker's compensation (NWC) patients. Nearly
      50% of the patients reported some type of transient or persistent side effect,
      mostly related to the infused substance. No mechanical failure of the DAS system
      was observed. Conclusion. These results in part replicate those from previous
      studies examining the long-term effects of infusion therapy. Side effects remain
      fairly common and require continued attention. Their presence, however, did not
      appear to deter from the patient's overall sense of satisfaction. Acquiring
      information from significant others and clinic staff may be a useful adjunct in
      interpreting the overall outcome.

PMID- 22151258
TI  - A method for training physicians to implant intrathecal catheters.

PMID- 22151259
TI  - Treatment of failed back surgery syndrome patients with low back and leg pain: a
      pilot study of a new dual lead spinal cord stimulation system.
AB  - Objective. Treatment of pain associated with failed back surgery syndrome was
      evaluated in a pilot clinical study of a new dual lead spinal cord stimulation
      (SCS) system. Methods. The following data was retrospectively sought from 20 non
      randomized patients at 2 centers treated by the new SCS system, instead of an
      implantable drug pump: 1) prior back surgeries, 2) pain and paresthesia mapping,
      3) VAS ratings, 4) medication use, 5) sleep patterns, 6) physical abilities, 7)
      hardware problems, and 8) willingness to repeat the procedure. Two-year follow-up
      was sought from all patients. Results. The new dual lead SCS system provided good
      low back and leg paresthesia coverage. Patients reported having less pain and
      using fewer analgesics and narcotics during follow-up, compared to their
      preimplant experience. These improvements were statistically significant.
      Patients also improved their sleep and physical abilities during follow-up. While
      external hardware problems occurred, 65% of dual lead SCS patients were willing
      to repeat the SCS implant procedure. Conclusions. Dual lead stimulation proved
      beneficial for patients with low back and leg pain associated with failed back
      surgery syndrome.

PMID- 22151260
TI  - Multiple Program Spinal Cord Stimulation in the Treatment of Chronic Pain: Follow
      Up of Multiple Program SCS.
AB  - Objective. Follow-up of 80 patients using multiple program spinal cord
      stimulation (SCS). Methods. For 30 months, we followed 80 chronic pain patients
      who had undergone SCS implantations at our center. Thirty-six patients had Failed
      Back Surgery Syndrome (FBSS). Patients were evaluated in patient-controlled
      stimulation mode (patients can select one of several specific programs in
      response to their activities and pain level). We collected visual analog pain
      scores, patient satisfaction scores, pain maps, and paresthesia maps. Results. We
      previously reported our preliminary findings (Neuromodulation 1998;1 :30-45). At
      24 months all patients were using more than one program. At 30 months, 62
      patients (76%) were using more than two programs as their preferred stimulation
      mode and three patients (4%) were satisfied with only one stimulation program. At
      30 months all patients chose patient-controlled stimulation as their preferred
      mode of stimulation. A total of 18 patients (23%) were explanted. Mean pain
      scores declined from 8.2 at baseline to 4.8 (p < 0.05, n= 79). Paresthesia
      overlap was 91% (n= 79). Of the patients with FBSS, 81% reported that they were
      using their SCS daily. Conclusions. In spinal cord stimulation the use of
      multiple electrodes and multiple stimulation programs, together with advanced
      programmability, increases paresthesia overlap, reduces pain scores, and may
      improve patient satisfaction with SCS therapy. This study indicates a significant
      patient preference for multiple program SCS, if patients are given the option to
      choose between a single program SCS system or a multiple program SCS system.

PMID- 22151261
TI  - Association of Left Ventricular Geometry With Left Atrial Enlargement in Patients
      With Preserved Ejection Fraction.
AB  - Left ventricular (LV) hypertrophy (LVH) is a known independent determinant of
      left atrial (LA) size; however, there is controversy regarding whether the LV
      geometric patterns are associated with LA enlargement (LAE), a major indicator of
      diastolic heart failure. The authors evaluated 47,865 patients with preserved
      ejection fraction to determine the relationship of LV geometry on LAE as
      determined by LA volume index (LAVi) 29 mL/m2. Abnormal LV geometry was
      identified in 48% and LAE was indentified in 43% with associated higher
      prevalence of abnormal LV geometry(59% vs 41%, P<.0001). Both LV mass index and
      relative wall thickness (RWT) were independent determinants of LAE (P<.0001).
      LAVi and prevalence of LAE differ significantly by LV geometric patterns
      (P<.0001). In multivariate analysis, abnormal LV geometry patterns, especially
      eccentric and concentric LVH, were independently associated with LAE. In
      conclusion, LAE assessed as increased LAVi is strongly associated not only with
      LV mass index but also with RWT. Furthermore, LAE was independently associated
      with abnormalities in LV geometry.

PMID- 22151262
TI  - Differentiation of live, dead and treated cells of Escherichia coli O157:H7 using
      FT-IR spectroscopy.
AB  - AIMS: To apply specific collection techniques and spectroscopy to differentiate
      between live and dead Escherichia coli O157:H7 cells, as well as cells subjected
      to various inactivation treatments, including heat, salt, UV, antibiotics and
      alcohol. METHODS AND RESULTS: Fourier transform-infrared (FT-IR) spectroscopy was
      used to analyse E. coli O157:H7 cells, after filtration or immunomagnetic
      collection. Partial least squares analysis of the spectra quantified live E. coli
      O157:H7 in the presence of dead cells with an R(2) > 0.996. Canonical variate
      analysis (CVA) not only differentiated between spectra of 100% dead and 100% live
      cells but also between 1% live : 99% dead and 100% dead. CVA using principal
      components also differentiated between the spectra of the differentially treated
      cells at a 95% confidence level, and Cooman plots showed clear separation between
      clusters of spectra of bacteria exposed to the different inactivation treatments.
      Mahalanobis distances (MD) corroborated the results of CVA. CONCLUSIONS: These
      results demonstrated the effectiveness of rapid cell collection and FT-IR
      spectroscopy techniques to differentiate between live and dead E. coli O157:H7
      cells. SIGNIFICANCE AND IMPACT OF THE STUDY: This technique has potential
      applications for use with foods subjected to various inactivation treatments.

PMID- 22151264
TI  - Evidence.

PMID- 22151265
TI  - Real-Time Paresthesia Steering Using ContinuousElectric Field Adjustment. Part I:
      IntraoperativePerformance.
AB  - We present data collected from a multicenter study using a new neurostimulation
      system. This new system uses a current-shifting programming technique for spinal
      cord stimulation. The system maintains a continuous, suprathreshold stimulation
      field while adjusting the distribution of anodic and cathodic current among
      contacts along a multi-contact array. The changing distribution of current shifts
      the electric field along the spinal cord, resulting in real-time, dynamic
      paresthesia steering. This process of adjusting the stimulation field has been
      termed continuous electric field adjustment (CEFA). This technique has been used
      to assess paresthesia coverage for patients undergoing implantation of
      stimulation contact arrays for chronic pain. This multicenter study evaluated the
      performance of the CEFA technique. The results of the study showed that
      paresthesia coverage could be shifted in real-time to different regions on the
      patient's body in a comfortable fashion, with the patient always feeling
      paresthesia during the adjustment process. The results of the study also show
      that the process was time-efficient: intraoperatively, the median time to assess
      71 combinations on a single 8-contact lead across 18 patients was 4.1 (3.6-5.0)
      minutes.

PMID- 22151263
TI  - Cross-talk between DNA methylation and active histone modifications regulates
      aberrant expression of ZAP70 in CLL.
AB  - Zeta-associated protein of 70 kD (ZAP70) is a recognized adverse prognostic
      marker in chronic lymphocytic leukaemia (CLL) associated with enhanced B-cell
      receptor signalling, significantly more aggressive disease course and poor
      overall survival. Zeta-associated protein of 70 kD is ordinarily expressed in T
      cells where it has a crucial role in T-cell receptor signalling, whereas its
      aberrant expression in CLL leads to enhanced B-cell receptor signalling and
      significantly more aggressive disease course. Although much is known about the
      activation of ZAP70 following engagement of T-cell receptor, there are little
      data on the regulation of ZAP70 gene expression in normal T cells or CLL. To
      understand the molecular events underpinning epigenetic regulation of ZAP70 gene
      in CLL, we have defined ZAP70 promoter region and outlined the regions crucial in
      regulating the gene activity. Following a direct comparison of ZAP70+ and ZAP70-
      primary CLLs, we show ZAP70 promoter in expressing CLLs to be associated with a
      spectrum of active histone modifications, some of which are tightly linked to
      aberrant DNA methylation in CLL. Cross-talk between histone modifications and
      reduced DNA methylation culminates in transcriptional de-repression of ZAP70.
      Moreover, treatment with histone deacetylase (HDAC) and DNA methylation
      inhibitors results in recovery of ZAP70 expression, which provides a possible
      explanation for the failure of HDAC inhibitors in CLL treatment and might serve
      as a cautionary warning for their future use in treatment of this leukaemia.

PMID- 22151266
TI  - Review of spinal cord stimulation in peripheral arterial disease.
AB  - Ever since its initial development in the late 1960s, spinal cord stimulation
      (SCS) has been used to treat a number of painful conditions. European practice,
      in contrast to that in North America, has used peripheral arterial disease (PAD)
      as a primary indication for SCS. First employed in patients with PAD in 1976, SCS
      was shown by Cook et al. to heal chronic leg ulcers. Numerous subsequent
      retrospective studies of SCS in PAD show improvements in multiple outcomes such
      as exercise tolerance, limb salvage, and pain. Previous retrospective studies are
      likely flawed with respect to author bias, inadequate sample size, and possible
      placebo effects. Further, they have not identified clinical criteria for
      selecting SCS therapy. Recent randomized prospective studies have questioned some
      of the conclusions from these preceding retrospective data. In addition to the
      questions related to outcomes, theories regarding exact mechanisms by which SCS
      improves circulatory parameters remain unclear. A thorough Medline literature
      review on the subject of SCS in peripheral vascular disease was thus undertaken
      to attempt to clarify questions regarding which patients are best suited for SCS
      therapy, pinpoint possible methodologic flaws in previous studies, and to review
      the background, outcomes, mechanisms of action, complications, and alternatives
      for SCS in patients with PAD.

PMID- 22151267
TI  - Phantom limb pain relieved with different modalities of central nervous system
      stimulation: a clinical and functional imaging case report of two patients.
AB  - Phantom limb pain (PLP) is a type of neuropathic pain syndrome that has evoked
      much interest in scientific and clinical fields. The condition is often
      intractable and severely debilitating. Though there are anecdotal reports in the
      literature of successful management of individual cases with brain and spinal
      cord stimulation, it has not been possible to develop a system of management that
      is consistently successful, mainly due to the paucity of basic neurophysiological
      data about PLP and its pathways in the central nervous system (CNS). Functional
      imaging offers a way of collecting information about the basic mechanisms and
      pathways of PLP from patients without the excessive risk of more invasive
      penetrating electrode studies or the questionable reliability of animal data.
      There have been very few studies that have looked at the direct effect of CNS
      stimulation on regional brain activation and correlation with the pain state. We
      describe two cases of PLP that have been satisfactorily treated with CNS
      stimulation (motor cortex and then periventricular gray in one and spinal cord in
      the other) and have been subjected to single photon emission computed tomography
      (SPECT) studies when in pain and then during stimulation with recorded pain
      relief. We found that regardless of the site of stimulation in the CNS, pain
      relief is associated with blood flow changes in similar areas of the brain,
      mainly the parietal and cingulate cortex and also in the thalamic nuclei and the
      central gray matter. Further studies of this kind should reveal more about the
      complex mechanisms of PLP and other forms of neuropathic pain.

PMID- 22151268
TI  - Neuropathic limb pain and spinal cord stimulation: results of the dutch
      prospective study.
AB  - Baseline and 12-month follow-up data from a prospective controlled study on
      patients treated with SCS for neuropathic limb pain (NLP) are analyzed
      critically. The outcome on pain, use of medication, and quality of life are
      reported and compared with the literature. Patients enrolled from April 1999 to
      December 2001 were part of a quality system study by the Dutch Working Group on
      Neuromodulation. In two years, more than 400 patients were admitted for several
      indications of chronic neuropathic pain. Failed back surgery syndrome (FBSS) and
      complex regional pain syndrome (CRPS) were the largest cohorts. FBSS was defined
      as persistent limb pain with/or without concomitant minor back pain after prior
      surgery for a slipped lumbar disc or spinal instability. SCS was a last resort
      therapy. Two criteria were used for eligibility: a SCL-90 score below 225 and a
      mean visual analog score (VAS) of four days according to Jensen of >= 5. One
      hundred sixty nine patients were registered for FBSS. Thirty four did not fulfill
      the eligibility criteria, and 135 received several questionnaires for baseline
      evaluation. Thirty patients did not have successful trial stimulation (< 50% pain
      relief), leaving 105 patients for implantation. The mean scores of the baseline
      evaluation were: SCL 137 (SD 28.3) and VAS 7.3 (SD 1.2), McGill pain
      questionnaire (MPQ) total PRI: 22.4 (9.4), Sickness Impact Profile (SIP) total
      score: 19.4 (SD10.1), ROLAND disability (RD) 16.9 (SD 3.5) and EUROQOL (EQ-5D)
      55.2 (SD 14.5) (simple linear index). Medication quantification scale at intake
      was 11.5 (SD 7.9). 56.2% of the patients used one or more narcotic drugs at
      intake. 82% of the patients did not have a paid job at the time of inclusion. 61%
      of the patients lost their job due to their medical problems. Scores at 12-m
      follow-up were VAS 3.0 (SD 2.4), MPQ 10.8 (SD 8), SIP 11.7 (SD 9.4), EQ-5D 38.2
      (SD 19.2) and RD 12.4 (SD 4.8). The difference between baseline and 12-m follow
      up is statistically significant for all measures. We conclude that the outcome
      measures indicate that SCS significantly reduces pain and enhances quality of
      life in patients having NLP not responding to other adjuvant therapy.
      Recommendations are proposed to make studies more comparable.

PMID- 22151269
TI  - Peripheral nerve stimulation: a percutaneous minimally invasive approach.
AB  - We report on the use of a new percutaneous technique for peripheral nerve
      stimulation (PNS) treatment of chronic pain. A 56-year-old woman was diagnosed
      with algodystrophic syndrome, now called Complex Regional Pain Syndrome, type 2
      (CRPS2), due to a lesion of the right medial nerve despite surgical
      revascularization, angioplasty and stent insertion. After a successful 10-day
      trial of PNS via a percutaneous quadripolar lead in the interscaline space, an
      implantable pulse generator was implanted in the abdominal subcutaneous tissue
      and connected to the subcutaneous lead via an extension. After one year of follow
      up, the patient was still experiencing good pain relief. We conclude that this
      novel percutaneous PNS technique offers the advantage of being a minimally
      invasive approach that can be easily adopted for the management of chronic pain.

PMID- 22151270
TI  - Stability and Analgesic Efficacy of Di-acetyl Morphine (Diamorphine) Compared
      with Morphine in Implanted Intrathecal Pumps In Vivo.
AB  - The objective of this study was to investigate di-acetyl morphine as an
      alternative opioid analgesic for use in implanted intrathecal drug delivery
      systems because of its greater solubility through evaluation of its stability in
      vivo and analgesic efficacy in the period between pump refills. Contents of
      intrathecal drug delivery system reservoirs (SynchroMed, Medtronic, Inc.,
      Minneapolis, MN) that had been filled with di-acetyl morphine dissolved in saline
      (21), bupivacaine (9), or in both bupivacaine and clonidine (19) were sampled in
      vivo between 1 and 125 days after refill. The samples were assayed for di-acetyl
      morphine and its breakdown products by micellar electrokinetic capillary
      chromatography. Prospective daily numerical pain scores between pump refills,
      using 11-point Likert scales, on 24 patients with implanted SynchroMed pumps (12
      delivering di-acetyl morphine in saline, 12 were delivering morphine in saline)
      were collected. Results showed that di-acetyl morphine immediately started to
      decay to mono-acetyl morphine in implanted Synchromed pumps with half-life of 50
      days. Mono-acetyl morphine decayed to morphine with a maxima estimated at 125
      days. There was no clinically significant change in average weekly pain scores
      for up to ten weeks in either group (range, 2.5 to 2.8 for diamorphine and 2.7 to
      3.1 for morphine) (2-way repeated ANOVA, F(9,220) = 0.98, n.s.). We conclude that
      di-acetyl morphine and its breakdown products, 6 mono-acetyl morphine and
      morphine, provide similar analgesia to morphine alone when administered by
      intrathecal pump for a period of at least ten weeks and may be a useful
      alternative when a more soluble agent is favored.

PMID- 22151271
TI  - Chronic Intrathecal Baclofen Infusion for Spasticity: Relationship between Pump
      and Host.
AB  - Twenty patients with chronic intractable spinal spasticity were implanted with a
      totally implantable programmable pump for intrathecal administration of baclofen.
      The objective of this study was to evaluate the relationship between pump and the
      host. Clinical efficacy of the therapy was evaluated by the Ashworth Scale, the
      Spasms Frequency Scale, and the Functional Independence Measure (FIM) motor
      scores. All patients were asked to reply to 10 questions regarding discomfort of
      their refills, the ease of rehabilitation after therapy, their fear of pump
      failure and onset of alarm signals, their discomfort due to a metallic foreign
      body (the pump), the attitude of their relatives and other persons regarding
      their pump system, whether they would undergo this therapy again, and whether, in
      the absence of public health insurance, whether they would be willing to pay for
      their pump and therapy. The Ashworth scale, the Spasms Frequency Scale, and the
      FIM motor score showed a significant improvement in all patients after the onset
      of therapy with baclofen. The refill procedure was not a problem in all patients
      while four patients (20%) considered the number of refills "uncomfortable."
      Rehabilitation was no problem after the pump was implanted in all patients, 10
      patients (50%) feared pump failure, while six patients (30%) feared their alarm
      signals. Three patients (15%) had some discomfort from their pumps rubbing
      against their belts; two patients (10%) stated that other people were aware of
      their pumps; all but two patients (10%) were ready to have their implants again;
      three patients (15%) would pay for the pump in case of absence of public health
      insurance for the therapy. We conclude that the implant of pumps for chronic
      intrathecal baclofen infusion is, today, a known effective procedure. Refill of
      the pump system was not a problem in our patient population, while the number of
      refills did cause some discomfort in some patients. It was shown by our study
      that the pump did facilitate rehabilitation in our patients, and a certain degree
      of dependence on the pump did exist. Fifty percent of the patients were afraid of
      pump failure and 30% were afraid of their alarm signals going off. The fact that
      most patients would undergo this therapy again and some would even pay for it
      directly in the absence of public insurance for the therapy were indices of
      patient satisfaction with the procedure. Because this was a small study, we
      believe that larger studies are necessary to corroborate our findings.

PMID- 22151272
TI  - Feasibility of gait event detection using intramuscular electromyography in the
      child with cerebral palsy.
AB  - The objective of this study was to develop and test the feasibility of a model
      that employs electromyographic (EMG) signals to predict the occurrence of gait
      events in the child with cerebral palsy (CP). This model could be the basis of a
      future functional electrical stimulation (FES) control system to assist gait. Two
      children were implanted with bifilar intramuscular electrodes into the quadriceps
      muscle bilaterally. Muscle activity and gait parameters were recorded, and a
      fuzzy inference system was used to correlate EMG to five distinct gait events.
      For nine of the 10 gait events evaluated, the model predicted gait events to
      within 82 ms on average, as referenced to the VICON motion analysis system. For
      eight of the 10 events, prediction errors were 0.3% or less. Results indicate
      that EMG from the proximal musculature could be used to predict the occurrence of
      gait events in these two children with CP.

PMID- 22151273
TI  - The effect of fatigue on the timing of electrical stimulation-evoked muscle
      contractions in people with spinal cord injury.
AB  - This study investigated the activation dynamics of electrical stimulation-evoked
      muscle contractions performed by individuals with spinal cord injury (SCI). The
      purpose was to determine whether electrical stimulation (ES) firing patterns
      during cycling exercise should be altered in response to fatigue-induced changes
      in the time taken for force to rise and fall with ES. Seven individuals with SCI
      performed isometric contractions and pedaled a motorized cycle ergometer with
      stimulation applied to the quadriceps muscles. Both exercise conditions were
      performed for five minutes while the patterns of torque production were recorded.
      ES-evoked knee extension torque fell by 75% under isometric conditions, and the
      rate of force rise and decline decreased in proportion to torque (r = 0.91, r =
      0.94, respectively). There was no change in the time for torque to rise to 50% of
      maximum levels. The time for torque to decline did increase slightly, but only
      during the first minute of exercise. Cycling power output fell approximately 50%
      during the five minutes of exercise, however, there was no change in the time
      taken for torque to rise or fall. The magnitude of ES-evoked muscle torques
      decline substantially with fatigue, however, the overall pattern of torque
      production remained relatively unchanged. These results suggest there is no need
      to alter stimulation firing patterns to accommodate fatigue during ES-evoked
      exercise.

PMID- 22151274
TI  - Wearable data collection system for online gait stability analysis.
AB  - We had shown in our previous research that the stability assessment and control
      are essential for generation of faster and more energy efficient functional
      electrical stimulation (FES) and/or crutch-assisted gait. The objective of our
      recent research work has been to design a wearable and portable system for gait
      stability analysis with online capabilities that is also applicable to crutch
      assisted gait modes. The developed wearable stability assessment system for as
      yet only biped gait consists of foot switches and goniometers attached to the leg
      joints. The instantaneous static and dynamic stability is, within the wearable
      system, assessed from the trajectory of the estimated body center of gravity
      (COG(HAT) ) and the supporting area shape/size as derived from step length and
      foot-floor contact state. We used motion analysis system data as reference for
      testing the wearable system accuracy. The wearable system was tested on five
      healthy subjects and one above-knee amputee. It proved to be reasonably accurate
      if compared to the classical, motion analysis system based method. However,
      additional work is required to port the system to the FES assisted and/or crutch
      assisted gait.

PMID- 22151275
TI  - Mixed electrical-chemical transmission between hippocampal mossy fibers and
      pyramidal cells.
AB  - Morphological and electrophysiological studies have shown that granule cell
      axons, the mossy fibers (MFs), establish gap junctions and therefore electrical
      communication among them. That granule cells express gap junctional proteins in
      their axons suggests the possibility that their terminals also express them. If
      this were to be the case, mixed electrical-chemical communication could be
      supported, as MF terminals normally use glutamate for fast communication with
      their target cells. Here we present electrophysiological studies in the rat and
      modeling studies consistent with this hypothesis. We show that MF activation
      produced fast spikelets followed by excitatory postsynaptic potentials in
      pyramidal cells (PCs), which, unlike the spikelets, underwent frequency
      potentiation and were strongly depressed by activation of metabotropic glutamate
      receptors, as expected from transmission of MF origin. The spikelets, which
      persisted during blockade of chemical transmission, were potentiated by dopamine
      and suppressed by the gap junction blocker carbenoxolone. The various waveforms
      evoked by MF stimulation were replicated in a multi-compartment model of a PC by
      brief current-pulse injections into the proximal apical dendritic compartment,
      where MFs are known to contact PCs. Mixed electrical and glutamatergic
      communication between granule cells and some PCs in CA3 may ensure the activation
      of sets of PCs, bypassing the strong action of concurrent feed-forward inhibition
      that granule cells activate. Importantly, MF-to-PC electrical coupling may allow
      bidirectional, possibly graded, communication that can be faster than chemical
      synapses and subject to different forms of modulation.

PMID- 22151276
TI  - Effectiveness of an integrated approach to reduce perinatal mortality: recent
      experiences from Matlab, Bangladesh.
AB  - BACKGROUND: Improving perinatal health is the key to achieving the Millennium
      Development Goal for child survival. Recently, several reviews suggest that
      scaling up available effective perinatal interventions in an integrated approach
      can substantially reduce the stillbirth and neonatal death rates worldwide. We
      evaluated the effect of packaged interventions given in pregnancy, delivery and
      post-partum periods through integration of community- and facility-based services
      on perinatal mortality. METHODS: This study took advantage of an ongoing health
      and demographic surveillance system (HDSS) and a new Maternal, Neonatal and Child
      Health (MNCH) Project initiated in 2007 in Matlab, Bangladesh in half
      (intervention area) of the HDSS area. In the other half, women received usual
      care through the government health system (comparison area). The MNCH Project
      strengthened ongoing maternal and child health services as well as added new
      services. The intervention followed a continuum of care model for pregnancy,
      intrapartum, and post-natal periods by improving established links between
      community- and facility-based services. With a separate pre-post samples design,
      we compared the perinatal mortality rates between two periods--before (2005-2006)
      and after (2008-2009) implementation of MNCH interventions. We also evaluated the
      difference-of-differences in perinatal mortality between intervention and
      comparison areas. RESULTS: Antenatal coverage, facility delivery and cesarean
      section rates were significantly higher in the post- intervention period in
      comparison with the period before intervention. In the intervention area, the
      odds of perinatal mortality decreased by 36% between the pre-intervention and
      post-intervention periods (odds ratio: 0.64; 95% confidence intervals: 0.52
      0.78). The reduction in the intervention area was also significant relative to
      the reduction in the comparison area (OR 0.73, 95% CI: 0.56-0.95; P = 0.018).
      CONCLUSION: The continuum of care approach provided through the integration of
      service delivery modes decreased the perinatal mortality rate within a short
      period of time. Further testing of this model is warranted within the government
      health system in Bangladesh and other low-income countries.

PMID- 22151277
TI  - DFT-based QSAR models to predict the antimycobacterial activity of chalcones.
AB  - In this study, antimycobacterial activity of a set of synthesized chalcone
      derivatives against Mycobacterium tuberculosis H37Rv was investigated by
      quantitative structure-activity relationship (QSAR) analysis using density
      functional theory (DFT) and molecular mechanics (MM+)-based descriptors in both
      gas and solvent phases. The best molecular descriptors identified were hardness,
      E(HOMO) , MR(A-4)  and MR(B-4')  that contributed to the antimycobacterial
      activity of the chalcones as independent factors. The correlation of these four
      descriptors with their antimycobacterial activity increases with the inclusion of
      solvent medium, indicating their importance in studying biological activity. QSAR
      models revealed that in gas phase, lower values of E(HOMO) , MR(A-4)  and MR(B
      4')  increase the antimycobacterial activity of the chalcone molecules. However,
      in solvent phase, lower values of E(HOMO)  and MR(B-4')  and higher values of
      MR(A-4)  increase their activity.

PMID- 22151278
TI  - Prevalence of patent foramen ovale with right-to-left shunting in dogs with
      pulmonic stenosis.
AB  - BACKGROUND: Right-to-left (R-L) shunt caused by patent foramen ovale (PFO)
      concurrent with pulmonic stenosis (PS) is considered common, although there is a
      lack of published evidence. OBJECTIVES: To investigate the prevalence of R-L
      shunt caused by a PFO in dogs with PS. ANIMALS: Thirty-one client-owned dogs with
      PS, without obvious extracardiac disease detected on the clinical examinations.
      METHODS: Case control study: R-L shunt probably caused by PFO was diagnosed when
      IV injected microbubbles appeared at the left atrial level with an intact atrial
      septum on echocardiography (bubble-positive dogs). The severity of PS concurrent
      tricuspid regurgitation (TR), relative thickness of the right ventricle, and
      relative right atrial area were compared between bubble-positive and bubble
      negative dogs. RESULTS: The prevalence of R-L shunts caused by PFO was 39% (12 of
      31 cases). The instantaneous pressure gradient (PG) across the pulmonic valve and
      relative thickness of the right ventricle were significantly increased in bubble
      positive compared with those in bubble-negative dogs. None of the dogs with mild
      or moderate PS (pressure gradient < 80 mm Hg, n = 2) demonstrated R-L shunt. The
      prevalence of TR in bubble-positive dogs was significantly higher than that in
      bubble-negative dogs. DISCUSSION AND CLINICAL RELEVANCE: Patent foramen ovale PFO
      with R-L shunt was more common in dogs with very severe PS and absent in dogs
      with mild PS.

PMID- 22151280
TI  - A real-time PCR for the detection and characterisation of Aspergillus species.
AB  - An early diagnosis of an invasive fungal infection is essential for the
      initiation of a specific antifungal therapy and to avoid unnecessary
      discontinuation of a baseline therapy for haematological or oncological diseases.
      A real-time PCR assay for the detection and strain identification of Aspergillus
      species from culture strains was evaluated. DNA preparation was evaluated in
      contaminated culture media, urine and serum. A LightCycler PCR to differentiate
      various Aspergillus species was established. A real-time PCR assay for the
      detection of Aspergillus species was improved and was able to detect and
      differentiate medically important Aspergillus spp. The sensitivity of the test
      was <10 plasmid equivalents/assay. The real-time PCR assay is a useful tool for
      the rapid identification of Aspergillus species and might be useful as an early
      diagnostic tool to detect an invasive fungal infection. A real-time PCR protocol
      was improved by generating plasmid standards, additional generation of melting
      curves for species identification and the correlation between the melting
      temperature and the nucleotide exchanges within the used 18S rRNA gene region.

PMID- 22151279
TI  - Detecting genomic regions associated with a disease using variability functions
      and Adjusted Rand Index.
AB  - BACKGROUND: The identification of functional regions contained in a given
      multiple sequence alignment constitutes one of the major challenges of
      comparative genomics. Several studies have focused on the identification of
      conserved regions and motifs. However, most of existing methods ignore the
      relationship between the functional genomic regions and the external evidence
      associated with the considered group of species (e.g., carcinogenicity of Human
      Papilloma Virus). In the past, we have proposed a method that takes into account
      the prior knowledge on an external evidence (e.g., carcinogenicity or invasivity
      of the considered organisms) and identifies genomic regions related to a specific
      disease. RESULTS AND CONCLUSION: We present a new algorithm for detecting genomic
      regions that may be associated with a disease. Two new variability functions and
      a bipartition optimization procedure are described. We validate and weigh our
      results using the Adjusted Rand Index (ARI), and thus assess to what extent the
      selected regions are related to carcinogenicity, invasivity, or any other species
      classification, given as input. The predictive power of different hit region
      detection functions was assessed on synthetic and real data. Our simulation
      results suggest that there is no a single function that provides the best results
      in all practical situations (e.g., monophyletic or polyphyletic evolution, and
      positive or negative selection), and that at least three different functions
      might be useful. The proposed hit region identification functions that do not
      benefit from the prior knowledge (i.e., carcinogenicity or invasivity of the
      involved organisms) can provide equivalent results than the existing functions
      that take advantage of such a prior knowledge. Using the new algorithm, we
      examined the Neisseria meningitidis FrpB gene product for invasivity and
      immunologic activity, and human papilloma virus (HPV) E6 oncoprotein for
      carcinogenicity, and confirmed some well-known molecular features, including
      surface exposed loops for N. meningitidis and PDZ domain for HPV.

PMID- 22151281
TI  - Influence of training load on upper respiratory tract infection incidence and
      antigen-stimulated cytokine production.
AB  - This study examined the effect of training load on upper respiratory tract
      infection (URTI) incidence in men and women engaged in endurance-based physical
      activity during winter and sought to establish if there are training-associated
      differences in immune function related to patterns of illness. Seventy-five
      individuals provided resting blood and saliva samples for determination of
      markers of systemic immunity. Weekly training and illness logs were kept for the
      following 4 months. Comparisons were made between subjects (n = 25) who reported
      that they exercised 3-6 h/week (LOW), 7-10 h/week (MED) or >= 11 h/week (HIGH).
      The HIGH and MED groups had more URTI episodes than the LOW group (2.4 +/- 2.8
      and 2.6 +/- 2.2 vs 1.0 +/- 1.6, respectively: P < 0.05). The HIGH group had
      approximately threefold higher interleukin (IL)-2, IL-4 and IL-10 production (all
      P < 0.05) by antigen-stimulated whole blood culture than the LOW group and the
      MED group had twofold higher IL-10 production than the LOW group (P < 0.05).
      Other immune variables were not influenced by training load. It is concluded that
      high levels of physical activity are associated with increased risk of URTI and
      this may be related to an elevated anti-inflammatory cytokine response to antigen
      challenge. 

PMID- 22151282
TI  - "On the shoulders of giants": a history of the understandings of pain, leading to
      the understandings of neuromodulation.
AB  - The history of the use of electrical stimulation for pain is a cavalcade of
      research and innovation of many great scholars, scientists, and physicians over
      centuries that continues up to the present day. The legacy of this philosophy,
      research, and innovation is the field of neuromodulation for pain control. Today,
      patients with chronic pain from damage to the nervous system and chronic pain of
      the extremities, the axial low back, and neck, the face, and the viscera, all
      derive benefit from these early pioneers that have led to the expanding field of
      neuromodulation ... "on the shoulders of giants." We present here a history of
      the understandings of pain from the ancients to the present, which has led to our
      understandings of the use of electricity to cure disease and release patients
      from their suffering, generating the new, exciting, and expanding field of
      neuromodulation.

PMID- 22151283
TI  - Implementing the SAFE Principles for the Development of Pain Medicine Therapeutic
      Algorithms That Include Neuromodulation Techniques.
AB  - Currently accepted chronic pain treatment algorithms have positioned therapies
      according to levels of invasiveness and up-front costs. After reviewing updated
      literature on efficacy and cost outcomes of care for patients with chronic pain
      that include interventional implantable technologies, we offer a new model of
      thinking when formulating algorithms of care that might include more invasive and
      costly interventions such as spinal cord stimulation, the SAFE principles. These
      SAFE principles include "safety,""appropriateness,""fiscal neutrality," and
      "efficacy."

PMID- 22151284
TI  - Heat flow from rechargeable neuromodulation systems into surrounding media.
AB  - A synergistic investigation involving both experiment and numerical simulation
      was performed in vitro to determine the heat flow from rechargeable
      neuromodulation systems into surrounding media. Each system consists of an
      implant and an external recharging antenna, and the heat flows of each of these
      components were determined separately. Three systems, each produced by a
      different medical device firm, were evaluated. The evaluated products included
      those from Medtronic Inc. (MDT), ANS (a St. Jude Company), and the Boston
      Scientific Company (BSC, formerly Advanced Bionics). To ensure statistical
      significance, three nominally identical samples of each of the three systems were
      included in the study. Furthermore, for each sample of each system, replicate
      evaluations were performed for both the implant and the antenna. It was found
      that for both components of MDT, substantially lower rates of heat flow were
      produced compared with those for ANS and BSC. With regard to the latter systems,
      the higher rates of heat flow were not consistently ordered for the implant and
      for the antenna. In general, replicate data runs for each system and each
      component were in satisfactory agreement. The different samples of the MDT system
      showed only minor deviations with regard to heat flow. The deviations among the
      different samples of both ANS and BSC were larger than those evidenced for MDT.

PMID- 22151285
TI  - Continuous morphine infusion: a retrospective study of efficacy, safety, and
      demographic variables.
AB  - Objectives.  This study aims to assess the efficacy of intrathecal infusion in
      different types of pain. A number of different variables were assessed to analyze
      their effect on therapy and to determine in which patients intrathecal infusion
      is more effective. Materials and Methods.  A retrospective study was conducted
      with data obtained from 1983 to 2002. During this period, 292 intrathecal
      morphine tests were performed, with positive results in 205 cases. Eight
      nonprogrammable intrathecal pumps and 205 programmable pumps were implanted. One
      hundred and thirty-one programmable pumps were studied in which the drug used was
      morphine alone. Efficacy and side-effects were analyzed in the overall sample,
      depending on the type of pain, gender, age (20-40, 40-64, > 65), and dose of
      morphine used (< 2, 2-4.9, 5-14.9, > 15). Results.  All results are expressed as
      median and interquartile range (p25-p75) because the data had a nonnormal
      distribution. The patients' mean age was 61 years (range 50-70 years); there were
      61 men (46.6%) and 70 women (53.4%). The most commonly reported pain types were
      cancer pain (64, 48.9%), neuropathic pain (51, 38.9%), and nociceptive pain (16,
      12.2%). Test dose used was 0.4 mg/day (0.2-0.7), and mean number of test days was
      6 days (range 4-9 days). The initial morphine dose was 0.50 mg (0.30-1.45), mean
      dose was 2.70 mg (1.25-6.20), and the final dose was 4 mg (0.0-47). The initial
      numerical rating scale score of 8 (8,9) decreased to 4 (3-8) and 2 (1-5) at the
      end of the study. The overall rate of complications was 35.35%. Relief was very
      good in 29 (50.4%), good in 66 (22.1%), fair in 20 (15.3%), and poor in 16
      (12.2%) patients. Univariate analysis. (Morphine): Gender: Male 49/58 (84.48%)
      vs. Female 43/65 (66.15%), RR 1.27 (1.04-1.57), p = 0.02 (chi-squared). No
      significant differences were found in the other variables studied (age and type
      of pain). The multivariate analysis (logistic regression analysis) revealed a
      significant difference with regard to gender, with an odds ratio of 2.78 in favor
      of male gender. When the efficacy and safety of the infusion was compared to the
      dose of morphine used, no significant differences were observed, with p = 0.65
      for efficacy and p = 0.69 for safety. Conclusions.  Pain relief was obtained with
      this technique in approximately 70% of patients, with no differences between pain
      types, but with a significant difference in favor of male gender.

PMID- 22151286
TI  - Distal baclofen pump catheter migration associated with far-lateral paraspinal
      surgical placement.
AB  - Objectives.  The increased rigidity and spasms implicit to patients being treated
      with baclofen provide a potential source of drug delivery system-related
      complications. Placement of the intrathecal catheter from the far-lateral
      paraspinal approach has been advocated to avoid catheter fracture as previously
      reported with a midline approach. A thin fascial layer and increased muscle bulk
      laterally could increase motion of catheters placed in this position. The authors
      report on a series of patients found to have spinal catheter migration out from
      the thecal sac following a far-lateral paraspinal surgical approach. Materials
      and Methods.  The medical records of six consecutive patients who required
      revision of an intrathecal baclofen infusion system secondary to spinal catheter
      migration were included in this retrospective review. Each patient failed to
      respond to oral antispasmodic therapy and showed a positive response to a trial
      of intrathecal baclofen before initial pump implantation. Clinical notes and
      operative reports were reviewed. Results.  All patients had a baclofen pump
      inserted with the intrathecal catheter placed through the far-lateral portion of
      the paraspinal musculature entering above the lumbar vertebral pedicle. In all
      cases, the spinal catheter migrated and was found coiled outside of the thecal
      sac. In two patients, this occurred on two separate occasions. Mean time to
      catheter revision following implantation was 7 +/- 2 months. Conclusions.  Spinal
      catheter migration from the subarachnoid space can occur with intrathecal
      baclofen infusion systems. Alternative methods for spinal catheter placement
      warrant further study.

PMID- 22151287
TI  - Effect of surface electrical stimulation of suprahyoid muscles on hyolaryngeal
      movement.
AB  - Objective.  This study aims to investigate the movements of hyolaryngeal
      structures during the surface electrical stimulation of suprahyoid muscles and to
      compare these with movements during liquid swallowing. Materials and methods. 
      Twelve volunteers without dysphagia participated in this study. Volunteers
      swallowed 5 mL of diluted barium liquid, which was recorded
      videofluoroscopically. They then received surface electrical stimulation at
      midpoints between the chin and the bilateral edges of the hyoid, and movements
      were again recorded. Two-dimensional motion analysis was performed and
      displacements of the hyoid and of subglottic air-column and epiglottic rotations
      were calculated. Movements caused by surface stimulation were compared to those
      during liquid swallowing. Results.  Elevation and anterior excursion of the hyoid
      by electrical stimulation were 66.8% and 45.2% of those during liquid swallowing,
      respectively, and rotation of the epiglottis by electrical stimulation was 24.0%
      of that during liquid swallowing. Elevation and anterior excursion of the
      subglottic air column during liquid swallowing were 24.1 mm and 4.6 mm,
      respectively, compared with 9.6 mm and 1.9 mm during electrical stimulation. All
      the movements during electrical stimulation were significantly smaller than those
      that occurred during liquid swallowing (p < 0.05). Trajectories of the hyoid and
      larynx during electrical stimulation were smaller than but similar to those that
      occurred during liquid swallowing. Conclusion.  This study suggests that surface
      electrical stimulation of suprahyoid muscles causes the elevation and anterior
      excursion of hyolaryngeal structures, as is observed during normal physiologic
      swallowing, although the movements involved were smaller. Further studies are
      required to determine the effect of synchronized electrical stimulation on
      dysphagia patients with reduced laryngeal elevation to allow the development of a
      swallow-assisting neural orthosis.

PMID- 22151288
TI  - Inhibition of cortical laser-evoked potentials by transcutaneous electrical nerve
      stimulation.
AB  - Objectives.  This study attempts to confirm the hypothesis that transcutaneous
      electrical stimulation (TENS) of peripheral Abeta fibers inhibits nociceptive
      processing, by quantifying the change of laser-evoked potential (LEP) components,
      using a 980-nm diode laser. Materials and Methods.  Cutaneous heat stimuli were
      delivered to the dorsum of the right hand in 13 volunteers. LEPs and pain
      intensity ratings were recorded before, during, and after the use of TENS (110
      Hz) at the dorsolateral forearm. Area under the curve (AUC), LEP amplitudes
      (N2P2), and peak latencies (N2, P2) were calculated. The paired samples t-test
      was used for statistical analysis. Results.  A significant reduction of LEP
      amplitudes and AUC was found during and after the use of TENS (p < 0.05). After
      10 min of TENS this was associated with a clinically relevant decrease of pain
      intensity. Conclusions.  Our data suggest that TENS inhibits nociceptive
      processing. Ten minutes of TENS exerts a clinically relevant pain reduction.

PMID- 22151289
TI  - Peripheral subcutaneous neurostimulation in the management of neuropathic pain:
      five case reports.
AB  - Introduction.  Spinal cord stimulation (SCS) is an effective treatment option for
      neuropathic pain. However, because of the obvious procedural issues, SCS is
      unable to reach certain areas, such as the face, thorax, coccyx, the cervico
      dorsal and lumbar areas, and the sacral, abdominal, and inguinal regions. On the
      other hand, these areas are easily reached by subcutaneous field stimulation.
      Methodology.  We report the analgesic results, using a visual analog scale (VAS),
      of five patients with neuropathic pain treated with subcutaneous field
      stimulation to the area. We also discuss the probable mechanism of action, and
      highlight the technical issues inherent to this approach. Results.  Significant
      pain reduction and reduction in analgesic medication were reported in all
      patients during the study period, with VAS scores consistently lowered by more
      than 50% from baseline levels. As a result of pain reduction, the patients'
      quality of life improved. There were no adverse events reported except for early
      electrode array displacement in two of our patients. Conclusion.  When SCS is not
      appropriate for certain neuropathic pain syndromes, subcutaneous field
      stimulation may be used with some degree of efficacy.

PMID- 22151290
TI  - Epidural Neurostimulation of Posterior Funiculi for the Treatment of Buerger's
      Disease.
AB  - Background.  Buerger disease is a nonatherosclerotic, segmental, occlusive and
      recurrent inflammatory vascular disorder that affects small and medium-sized
      arteries and veins of the upper and lower extremities. Case reports.  We report
      two cases of Buerger disease. Medical History.  Smoking habit. No autoimmune
      diseases. No diabetes mellitus. Intermittent vascular claudication at 100-150 m.
      Several hospital admissions for amputations. Prior Medical Treatment. 
      Antiplatelet agents, vasodilators, nonsteroidal anti-inflammatory drugs, third
      step analgesics, fibrinolytic treatment and lumbar sympathectomies. Following all
      of the above treatments, Synergy((r)) spinal cord (ECP) stimulator with two
      electrodes (Quad PISCES((c)) ) placed at the level of T9-T10. Results.  There has
      been a reduction in pain of about 80% and an improvement of intermittent
      claudication (one of the patients no longer claudicates, whereas the other
      patient claudicates at 400 m). Conclusion.  Neurostimulation of the posterior
      funiculi could be considered not only as palliative care but also as a
      therapeutic option.

PMID- 22151291
TI  - Rare Side-effects during Spinal Cord Stimulation: Gastrointestinal Symptoms.
AB  - In current medical literature, most reported complications during spinal cord
      stimulation (SCS) concern technical problems, such as malfunction, migration or
      breakage of the lead, or internal pulse generator dysfunction, while reports
      about side-effects caused by SCS are rare. In this clinical report, we describe
      uncommon and unexplained gastrointestinal (GI) side-effects of constipation,
      abdominal pain, and distension during SCS in a patient suffering for chronic
      neuropathic pain caused by failed back surgery syndrome. These GI symptoms
      disappeared after suspension of SCS and were reduced if the stimulation settings
      were reduced below paresthesia threshold. The symptoms experienced by our patient
      could be related to a functional and reversible block of parasympathetic outflow
      in the GI system since SCS may involve not only dorsal horn structures but also
      somatic and visceral sensory afferents to these structures in an unpredictable
      way.

PMID- 22151292
TI  - Intrathecal morphine therapy-related granulomas: faster to grow than thought.
AB  - Complications of intrathecal drug delivery are relatively rare. Of these,
      infections, cutaneous erosion, and granulomas account for the most common
      complications. The latter is often noticed when the patient shows signs of
      sedation and/or reduced pain relief. Granulomas have always been considered to
      develop over a long period of time, usually calculated in months. Here, we
      present a case where a catheter-tip granuloma formed within 5 weeks of
      intrathecal morphine. The patient was carrying an intrathecal pump for 3 months
      when it was diagnosed. Probable causes of the formation are discussed.

PMID- 22151293
TI  - Response to weinmann and sparrow "heat flow from rechargeable neuromodulation
      systems into surrounding media".

PMID- 22151294
TI  - Response to weinmann and sparrow "heat flow from rechargeable neuromodulation
      systems into surrounding media".

PMID- 22151295
TI  - Response to weinmann and sparrow "heat flow from rechargeable neuromodulation
      systems into surrounding media".

PMID- 22151296
TI  - Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe
      COPD: the GLOW1 trial.
AB  - BACKGROUND: NVA237 is a once-daily dry-powder formulation of the long-acting
      muscarinic antagonist glycopyrronium bromide in development for the treatment of
      chronic obstructive pulmonary disease (COPD). The glycopyrronium bromide in COPD
      airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability
      of NVA237 in patients with moderate-to-severe COPD. METHODS: Patients with COPD
      with a smoking history of >= 10 pack-years, post-bronchodilator forced expiratory
      volume in 1 second (FEV1) < 80% and >= 30% predicted normal and FEV1/forced vital
      capacity < 0.70 were enrolled. Patients were randomized to double-blind treatment
      with NVA237 50 MUg once daily or placebo for 26 weeks with inhaled/intranasal
      corticosteroids or H1 antagonists permitted in patients stabilized on them prior
      to study entry. The primary outcome measure was trough FEV1 at Week 12. RESULTS:
      A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).
      Least squares mean (+/- standard error) trough FEV1 at Week 12 was significantly
      higher in patients receiving NVA237 (1.408 +/- 0.0105 L), versus placebo (1.301
      +/- 0.0137 L; treatment difference 108 +/- 14.8 mL, p < 0.001). Significant
      improvements in trough FEV1 were apparent at the end of Day 1 and sustained
      through Week 26. FEV1 was significantly improved in the NVA237 group versus
      placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at
      all other visits and timepoints. Transition dyspnoea index focal scores and St.
      George's Respiratory Questionnaire scores were significantly improved with NVA237
      versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and 
      2.81 (p = 0.004), respectively. NVA237 significantly reduced the risk of first
      moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication
      by 0.46 puffs per day (p = 0.005), versus placebo. NVA237 was well tolerated and
      had an acceptable safety profile, with a low frequency of cardiac and typical
      antimuscarinic adverse effects. CONCLUSIONS: Once-daily NVA237 was safe and well
      tolerated and provided rapid, sustained improvements in lung function,
      improvements in dyspnoea, and health-related quality of life, and reduced the
      risk of exacerbations and the use of rescue medication. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01005901.

PMID- 22151298
TI  - The Wound CARE Instrument: the process for developing standards for wound
      management education and programming.
AB  - This article describes the collaborative process undertaken by the Canadian
      Association for Enterostomal Therapy and the Canadian Association of Wound Care
      in an effort to improve the quality of wound prevention and management education
      and programming. The end result of this process is the Wound CARE Instrument
      which promotes an interprofessional, collaborative appraisal process to support
      the development, adoption or adaption of wound management educational events and
      programs.

PMID- 22151297
TI  - Stopping rules employing response rates, time to progression, and early
      progressive disease for phase II oncology trials.
AB  - BACKGROUND: Response rate (RR), the most common early means of assessing oncology
      drugs, is not suitable as the sole endpoint for phase II trials of drugs which
      induce disease stability but not regression. Time to progression (TTP) may be
      more sensitive to such agents, but induces recruitment delays in multistage
      studies. Early progressive disease (EPD) is the earliest signal of time to
      progression, but is less intuitive to investigators, To study drugs with unknown
      anti-tumour effect, we designed the Combination Stopping Rule (CSR), which allows
      investigators to establish a hypothesis using RR and TTP, while the program also
      employs early progressive disease (EPD) to assess for drug inactivity during the
      first stage of study accrual. METHODS: A computer program was created to generate
      stopping rules based on specified error rates, trial size, and RR and median TTP
      of interest and disinterest for a two-stage phase II trial. Rules were generated
      for stage II such that the null hypothesis (H(nul)) was rejected if either RR or
      TTP met desired thresholds, and accepted if both did not. Assuming an exponential
      distribution for progression, EPD thresholds were determined based on specified
      TTP values. Stopping rules were generated for stage I such that Hnul was accepted
      and the study stopped if both RR and EPD were unacceptable. RESULTS: Patient
      thresholds were generated for RR, median TTP, and EPD which achieved specified
      error rates and which allowed early stopping based on RR and EPD. For smaller
      proportional differences between interesting and disinteresting values of RR or
      TTP, larger trials are required to maintain alpha error, and early stopping is
      more common with a larger first stage. CONCLUSION: Stopping rules are provided
      for phase II trials for drugs which have either a desirable RR or TTP. In
      addition, early stopping can be achieved using RR and EPD.

PMID- 22151299
TI  - The effect of training administered to working mothers on maternal anxiety levels
      and breastfeeding habits.
AB  - AIM AND OBJECTIVE: This study was conducted to determine the effect of training
      administered to working mothers and its duration on maternal anxiety levels and
      breastfeeding habits. BACKGROUND: Within the scope of Health for All in the 21st
      Century project, a goal was set to increase the rate of infants fed exclusively
      by breastfeeding during the first six months of life to 80% by the year 2015.
      DESIGN: A randomised design with repeated measures. METHODS: During collection of
      pretest data, a Personal Information Form, a Questionnaire Form and a State Trait
      Anxiety Inventory were administered to the mothers in the experimental and
      control groups. Five home visits were conducted starting two weeks before the
      date when mothers returned to work and ending when the infants became six months
      old. Breastfeeding techniques were taught to these mothers. Data were subjected
      to Proc MEAN, FREQ, anova and GENMOD procedures. RESULTS: The rate of natural
      feeding (breastfeeding exclusively) among trained mothers was greater than
      untrained mothers. The frequency of breastfeeding affects maternal anxiety
      levels; the anxiety level of mothers decreased with increasing frequency of
      breastfeeding. CONCLUSION: Educating working mothers about breastfeeding reduces
      their anxiety levels and influences positively their breastfeeding habits.
      RELEVANCE TO CLINICAL PRACTICE: With the support of health-care staff to increase
      awareness and knowledge on the value and sufficiency of breast milk, the rate and
      period of natural feeding increased significantly among working mothers.

PMID- 22151300
TI  - Temporary vision loss because of dimethyl sulfoxide in autologous stem cell
      transplantation.

PMID- 22151301
TI  - Implanted adipose-derived stem cells attenuate small-for-size liver graft injury
      by secretion of VEGF in rats.
AB  - Graft injury after small-for-size liver transplantation impairs graft function
      and threatens the survival of the recipients. The use of adipose-derived stem
      cells (ADSCs) for liver injury protection and repair is promising. Our aim was to
      investigate the role of vascular endothelial growth factor (VEGF) secreted by
      ADSCs in the treatment of small-for-size liver graft injury. Studies were
      performed using ADSCs with VEGF secretion blocked by RNA interference. In vitro,
      ADSCs prevented apoptosis of freshly isolated liver sinusoidal endothelial cells
      (LSECs) by secretion of VEGF. Syngeneic 35% orthotopic liver transplantation
      followed by implantation of syngeneic ADSCs through the portal vein system was
      performed using Wistar rats. We found VEGF secreted by implanted ADSCs improved
      graft microcirculatory disturbances, serum liver function parameters and
      survival. The improved microcirculatory status was also reflected by reduced
      hepatocellular damage, especially LSEC apoptosis and improved liver regeneration.
      These effects were accompanied by decreased expression of endothelin receptor
      type A, increased Bcl-2/Bax ratio, decreased expression of Bad and elevated
      proportion of phosphorylated Bad. In conclusion, implanted syngeneic ADSCs
      attenuated small-for-size liver graft injuries and subsequently enhanced liver
      regeneration in a rat 35% liver transplantation model. The VEGF secreted by
      implanted ADSCs played a crucial role in this process.

PMID- 22151302
TI  - Expression of delta-catenin is associated with progression of human astrocytoma.
AB  - BACKGROUND: delta-Catenin (CTNND2), which encodes a scaffold protein in humans,
      has been found in a few malignancies. However, the expression pattern and
      contribution of delta-catenin to astrocytoma progression are unclear. METHODS: We
      investigated delta-catenin expression in human astrocytoma samples and its
      function in astrocytoma cell lines using immunohistochemistry, siRNA knockdown,
      transfection, MTT, transwell migration and Rac1 pulldown techniques. RESULTS:
      delta-Catenin protein expression was detected in cytoplasm of astrocytoma cells
      by immunohistochemistry. Analysis showed that grade I astrocytoma (0%, 0/11) and
      glial cells from normal brain tissue exhibited negative staining. delta-Catenin
      expression was significantly higher in grade III-IV (35%, 29/84) compared to
      grade II astrocytoma cells (18%, 11/61); p < 0.01). In addition, CTNND2
      overexpression promoted proliferation, invasion and Rac1 activity of U251
      astrocytoma cells. Treatment of delta-catenin-transfected cells with a Rac1
      inhibitor decreased Rac1 activity and invasion. delta-Catenin knockdown in U87
      glioblastoma cell decreased cell proliferation, invasion and Rac1 activity.
      CONCLUSION: The results suggest that delta-catenin expression is associated with
      the malignant progression of astrocytoma and promotes astrocytoma cell invasion
      through upregulation of Rac1 activity. delta-Catenin expression levels may serve
      as a useful marker of the biological behavior of astrocytoma cells.

PMID- 22151303
TI  - XIAO is involved in the control of organ size by contributing to the regulation
      of signaling and homeostasis of brassinosteroids and cell cycling in rice.
AB  - Organ size is determined by cell number and size, and involves two fundamental
      processes: cell proliferation and cell expansion. Although several plant hormones
      are known to play critical roles in shaping organ size by regulating the cell
      cycle, it is not known whether brassinosteroids (BRs) are also involved in
      regulating cell division. Here we identified a rice T-DNA insertion mutant for
      organ size, referred to as xiao, that displays dwarfism and erect leaves, typical
      BR-related phenotypes, together with reduced seed setting. XIAO is predicted to
      encode an LRR kinase. The small stature of the xiao mutant resulted from reduced
      organ sizes due to decreased cell numbers resulting from reduced cell division
      rate, as supported by the observed co-expression of XIAO with a number of genes
      involved in cell cycling. The xiao mutant displayed a tissue-specific enhanced BR
      response and greatly reduced BR contents at the whole-plant level. These results
      indicated that XIAO is a regulator of BR signaling and cell division. Thus, XIAO
      may provide a possible connection between BRs and cell-cycle regulation in
      controlling organ growth.

PMID- 22151304
TI  - TPV1, the first virus isolated from the hyperthermophilic genus Thermococcus.
AB  - We describe a novel virus, TPV1 (Thermococcus prieurii virus 1), which was
      discovered in a hyperthermophilic euryarchaeote isolated from a deep-sea
      hydrothermal chimney sample collected at a depth of 2700 m at the East Pacific
      Rise. TPV1 is the first virus isolated and characterized from the
      hyperthermophilic euryarchaeal genus Thermococcus. TPV1 particles have a lemon
      shaped morphology (140 nm * 80 nm) similar to the structures previously reported
      for Fuselloviruses and for the unclassified virus-like particle PAV1 (Pyrococcus
      abyssi virus 1). The infection with TPV1 does not cause host lysis and viral
      replication can be induced by UV irradiation. TPV1 contains a double-stranded
      circular DNA of 21.5 kb, which is also present in high copy number in a free form
      in the host cell. The TPV1 genome encompasses 28 predicted genes; the protein
      sequences encoded in 16 of these genes show no significant similarity to proteins
      in public databases. Proteins predicted to be involved in genome replication were
      identified as well as transcriptional regulators. TPV1 encodes also a predicted
      integrase of the tyrosine recombinase family. The only two genes that are
      homologous between TPV1 and PAV1 are TPV1-22 and TPV1-23, which encode proteins
      containing a concanavalin A-like lectin/glucanase domain that might be involved
      in virus-host recognition.

PMID- 22151305
TI  - Immunological mechanisms of contact hypersensitivity in mice.
AB  - Contact hypersensitivity (CHS) is an animal model in which the immunological
      mechanisms of allergic contact dermatitis (ACD) in humans can be studied but is
      also widely used in the study of many basic immunological mechanisms. In CHS, a
      pre-sensitized animal is re-exposed to an antigen, thereby eliciting an
      immunological reaction at the site of antigen exposure. CHS consists of two
      phases: sensitization and elicitation phase. In the sensitization phase, the
      first contact of the skin with a hapten leads to binding of the hapten to an
      endogenous protein in the skin where they form hapten-carrier complexes which are
      immunogenic. The hapten-carrier complex is taken up by Langerhans cells (LCs) and
      dermal dendritic cells (dDCs) which migrate from the epidermis to the draining
      lymph node. Here, they present the haptenated peptides to naive T cells which are
      subsequently activated. The newly activated T cells proliferate and migrate out
      of the lymph node and into circulation. In the elicitation phase, re-exposure of
      the skin to the hapten activates the specific T cells in the dermis and triggers
      the inflammatory process responsible for the cutaneous lesions. Originally CHS
      was regarded as being solely driven by T cells but recently other cell types such
      as B1 cells, natural killer (NK) T cells and NK cells have shown to mediate
      important functions during the response as well. Here, we have described the
      molecular and cellular pathways in the development of CHS and have focused on
      recent advances and novel knowledge in the understanding of the immunoregulatory
      mechanisms involved in CHS.

PMID- 22151306
TI  - Prognostic role of integrin beta1, E-cadherin, and rac1 expression in small cell
      lung cancer.
AB  - Integrin beta(1) mediates cellular adhesion to the extracellular matrix (ECM) and
      is correlated with highly invasive and metastatic behavior in small cell lung
      cancer (SCLC). E-cadherin (ECAD) is a calcium-dependent cell-cell adhesion
      receptor that restricts invasion of cells and reduces metastasis. Rac1 is
      involved in the regulation of the actin cytoskeleton, adhesion, migration,
      invasion, and tumor metastasis. The aim of this study was to examine integrin
      beta(1) , ECAD and rac1 expression in SCLC and to analyze the prognostic value of
      these markers in patients with SCLC. We analyzed integrin beta(1) , ECAD, and
      rac1 expression in 112 SCLC tissues by immunohistochemical staining. Correlative
      analyses between integrin beta(1) , ECAD, and rac1 expression and
      cliniopathological factors were performed. A total of 65 patients had extensive
      disease (ED) (58%), and 47 had limited disease (LD) (42%). The median follow-up
      duration was 61 months (range: 14-117 months), and the median progression free
      survival (PFS) and overall survival (OS) were 6.1 months (range: 4.8-7.4 months)
      and 9.7 months (range: 8.1-11.3 months), respectively. The expression of integrin
      beta(1) , ECAD, and rac1 protein was observed in 64, 73, and 99 of SCLC tissues,
      respectively. The correlative analyses between integrin beta(1) , ECAD, or rac1
      expression and various clinical parameters did not show any statistical
      significance. However, the ECAD expression was associated with OS in the entire
      cohort. In contrast, the expression of integrin beta(1) and rac1 was not
      associated with PFS or OS. In a subgroup analysis, patients with less than two
      metastasis had significantly longer OS (p = 0.047) if their tumors expressed
      integrin beta(1) compared to those without integrin beta(1) expression. In
      addition, OS was longer for patients with ECAD positive tumors compared to those
      whose tumors did not express ECAD in males (p = 0.032) and patients who never
      smoked (p < 0.001). Multivariate analysis showed that LD (p = 0.004), overall
      response rate (p = 0.003), and expression of ECAD (p = 0.015) were the
      independent good prognostic factors for OS. LD (p = 0.024), overall response rate
      (p < 0.001), and less than two metastasis (p = 0.003) were prognostic factors for
      longer PFS. These results suggest that ECAD expression may be useful as a
      prognostic indicator in patients with SCLC.

PMID- 22151307
TI  - The use of whole-cell protein profile analysis by SDS-PAGE as an accurate tool to
      identify species and subspecies of coagulase-negative staphylococci.
AB  - We used sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as a
      tool to characterize coagulase-negative staphylococci (CoNS). Of 253 clinical
      isolates and 10 control strains, five species and four subspecies were analyzed.
      All the isolates were identified using conventional phenotypic tests and SDS
      PAGE. Discrepant results between these methods, as well as less common species
      and subspecies, were confirmed by sodA and 16S rDNA gene sequencing. Intraspecies
      similarities, calculated by the Dice coefficient, were significantly higher when
      compared to interspecies similarities. The conventional method failed to identify
      eight (3.2%) molecularly defined and SDS-PAGE-determined isolates. Therefore, SDS
      PAGE was able to discriminate between all unidentified or misidentified isolates
      using a phenotypic method. In addition, SDS-PAGE identified all atypical isolates
      using biochemistry and CoNS at the subspecies level.

PMID- 22151308
TI  - Toxoplasma gondii excretory secretory antigenic proteins of diagnostic potential.
AB  - Infection with Toxoplasma gondii is widespread and important in humans,
      especially pregnant women and immunosuppressed patients. A panel of tests is
      usually required for diagnosis toxoplasmosis. Excretory secretory antigen (ESA)
      is highly immunogenic, and thus it is a good candidate for investigation into new
      infection markers. ESA was prepared from tachyzoites of RH strain of T. gondii by
      mice intraperitoneal infection. Sera were obtained from several categories of
      individuals who differed in their status of anti-Toxoplasma IgM, IgG and IgG
      avidity antibodies. The ESA was subjected to SDS-PAGE, two-dimensional gel
      electrophoresis and Western blot analysis. Antigenic bands of approximate
      molecular weights of 12, 20 and 30 kDa, when probed with anti-human IgM-HRP and
      IgA-HRP, showed good potential as infection markers. The highest sensitivity of
      the bands was 98.7% with combination of IgM and IgA blots with sera of patients
      with anti-Toxoplasma IgM+ IgG+. The specificities were 84% and 70% with sera from
      other infections and healthy controls in IgM blots and IgA blots respectively. By
      mass spectrometry, the 12 kDa protein was identified as thioredoxin. The two top
      proteins identified for 20 kDa molecule were microneme protein 10 and dense
      granule protein 7; whereas that for 30 kDa were phosphoglycerate mutase 1 and
      phosphoglycerate mutase.

PMID- 22151309
TI  - Characterization of recombinant Streptococcus mitis-derived human platelet
      aggregation factor.
AB  - We previously purified Streptococcus mitis-derived human platelet aggregation
      factor (Sm-hPAF) from the culture supernatant of S. mitis strain Nm-65, isolated
      from the tooth surface of a patient with Kawasaki disease. Here we produced
      recombinant Sm-hPAF protein (rSm-hPAF) in Escherichia coli, to determine whether
      rSm-hPAF conserves its platelet aggregation activity. rSm-hPAF precursor (665
      amino acids) shows up to 36-56% identity with the family of cholesterol-dependent
      cytolysins (CDCs), and rSm-hPAF displayed potent hemolytic activity toward
      mammalian erythrocytes, including human erythrocytes with platelet aggregation
      activity. The 162-amino acid amino-terminal domain of rSm-hPAF was found in no
      other CDCs except lectinolysin; this domain is homologous to a portion of
      pneumococcal fucolectin-related protein. Interestingly, suilysin (SLY) and
      pneumolysin (PLY) of CDCs also exhibit substantial human platelet aggregation
      activity, similar to rSm-hPAF, and the platelet aggregation by rSm-hPAF, SLY, and
      PLY was morphologically confirmed using light and electron microscopy.

PMID- 22151310
TI  - Recombinant BCG coexpressing Ag85B, CFP10, and interleukin-12 induces
      multifunctional Th1 and memory T cells in mice.
AB  - Mycobacterium tuberculosis (MTB) continues to be a leading cause of human deaths
      due to an infectious agent. Current efforts are focused on making better TB
      vaccines. We describe the generation and immunological characterization of
      recombinant BCG (rBCG). This rBCG was generated by incorporating an expression
      plasmid encoding two mycobacterial antigens (Ag85B and CFP10) and human
      interleukin (IL)-12 into a BCG strain. Immunogenicity studies in mice showed that
      rBCG coexpressing Ag85B, CFP10, and IL-12 (rBCG::Ag85B-CFP10-IL-12) induces a
      robust immune response in mice. The rBCG vaccine promotes a T-cell response
      against MTB that is characterized by a high proportion of polyfunctional and
      memory T cells in spleen and lung. Our results showed strong immunogenicity and
      mycobacterial growth inhibition of rBCG::Ag85B-CFP10 plus IL-12 than that of BCG
      vaccine.

PMID- 22151311
TI  - Myoepithelial carcinoma and epithelial-myoepithelial carcinoma of the paranasal
      sinuses: two distinct entities.

PMID- 22151312
TI  - Thoracic spinal cord stimulation improves cardiac contractile function and
      myocardial oxygen consumption in a porcine model of ischemic heart failure.
AB  - BACKGROUND: Prior experimental studies show that thoracic spinal cord stimulation
      (SCS) improves left ventricular (LV) ejection fraction (LVEF). The mechanism of
      this improvement in the LV contractile function after SCS and its effects on the
      myocardial oxygen consumption remains unknown. METHODS AND RESULTS: We performed
      thoracic SCS (T1-T2 level) followed by 4 weeks of rapid ventricular pacing in 9
      adult pigs with ischemic heart failure (HF) induced by myocardial infarction
      (MI). At 24 hours off-pacing, detailed echocardiogram and invasive hemodynamic
      assessment were performed to determine LV contractile function and myocardial
      oxygen consumption. Serum norepinephrine level was measured before and after SCS.
      SCS was performed on 2 occasions for 15 minutes, 30 minutes apart (recovery) with
      50 Hz frequency (pulse width 0.2 millisecond, 90% of motor threshold at 2 Hz
      output). Echocardiogram revealed significant decrease in LVEF (33.8 +/- 1.8% vs
      66.5 +/- 1.7%, P < 0.01) after induction of MI and HF. Compared with MI and HF,
      acute SCS significantly increased LVEF and +dP/dt (all P < 0.05). Withdrawal of
      SCS during recovery decreased +dP/dt, but not LVEF that increased again with
      repeated SCS. Myocardial oxygen consumption also significantly decreased during
      SCS compared with MI and HF (P = 0.006) without any change in serum
      norepinephrine level (P = 0.9). Speckle tracking imaging showed significant
      improvement in global and regional circumferential strains over the infarcted mid
      and apical regions, decreased in time to peak circumferential strain over the
      lateral and posterior wall after SCS, and the degree of intraventricular
      dyssynchrony during SCS compared with MI and HF (P < 0.05). CONCLUSIONS: In a
      porcine model of ischemic HF, acute SCS improved global and regional LV
      contractile function and intraventricular dyssynchrony, and decreased myocardial
      oxygen consumption without elevation of norepinephrine level.

PMID- 22151313
TI  - Addressing the deluge of early release prisoners into US communities.

PMID- 22151314
TI  - Misleading conclusions from clinical research.

PMID- 22151315
TI  - Does definition matter? Is a concept of chronic, relapsing disorders a source of
      dominant policy and treatment paradigm or its reflection?

PMID- 22151316
TI  - The alcohol dependence concept is not as useful for science as it is for
      practice.

PMID- 22151317
TI  - Where are we going? A further question for the addiction field.

PMID- 22151318
TI  - Alcohol consumption and the intention to engage in unprotected sex: systematic
      review and meta-analysis of experimental studies.
AB  - AIMS: To review and analyse in experimentally controlled studies the impact of
      alcohol consumption on intentions to engage in unprotected sex. To draw
      conclusions with respect to the question of whether alcohol has an independent
      effect on the incidence of human immunodeficiency virus (HIV) and other sexually
      transmitted infections (STIs). METHODS: A systematic review and meta-analysis of
      randomized controlled studies examined the association between blood alcohol
      content (BAC) and self-perceived likelihood of using a condom during intercourse.
      The systematic review and meta-analysis were conducted according to
      internationally standardized protocols (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses: PRISMA). The meta-analysis included an estimate of the
      dose-response effect, tests for publication bias and sensitivity analyses.
      RESULTS: Of the 12 studies included in the quantitative synthesis, our pooled
      analysis indicated that an increase in BAC of 0.1 mg/ml resulted in an increase
      of 5.0% (95% CI: 2.8-7.1%) in the indicated likelihood (indicated by a Likert
      scale) of engaging in unprotected sex. After adjusting for potential publication
      bias, this estimate dropped to 2.9% (95% CI: 2.0-3.9%). Thus, the larger the
      alcohol intake and the subsequent level of BAC, the higher the intentions to
      engage in unsafe sex. The main results were homogeneous, persisted in sensitivity
      analyses and after correction for publication bias. CONCLUSIONS: Alcohol use is
      an independent risk factor for intentions to engage in unprotected sex, and as
      risky sex intentions have been shown to be linked to actual risk behavior, the
      role of alcohol consumption in the transmission of HIV and other STIs may be of
      public health importance.

PMID- 22151319
TI  - Commentary on Caetano et al. (2012): Beyond exhortations for drinkers to drink
      less.

PMID- 22151320
TI  - Commentary on Thorne et al. (2012): HIV prevention and treatment in female
      injection drug users--a work in progress.

PMID- 22151321
TI  - Commentary on Burton et al. (2012): The influence of tobacco retail merchandising
      on tobacco consumption.

PMID- 22151322
TI  - Joseph Vincent Brady (1922-2011): Behavioral neuropharmacologist, but so much
      more.

PMID- 22151324
TI  - A randomized experiment to examine unintended consequences of dietary supplement
      use among daily smokers: taking supplements reduces self-regulation of smoking.

PMID- 22151325
TI  - Payment by results can increase the availability of smoking cessation services
      while improving quality and equity.

PMID- 22151328
TI  - Determining the disinfection of textiles in compressed carbon dioxide using
      various indicator microbes.
AB  - AIMS: This paper presents a research on the disinfection efficiency of inoculated
      textile swatches by compressed carbon dioxide, an environmental friendly way to
      disinfect textiles as opposed to the conventional laundering procedures using
      water. The disinfection efficiency was determined by using the following microbes
      inoculated on cotton test fabrics: Enterococcus faecium, Enterobacter aerogenes
      and Candida albicans. METHODS AND RESULTS: The experiments were performed using
      the high pressure extraction device with a maximum pressure of 50MPa and a small
      extraction vessel of 500ml. Pure CO(2) and CO(2) with added disinfection agent or
      commercial detergent were used. The chosen disinfecting agent was hydrogen
      peroxide, a widespread disinfecting chemical. It was found that treatment with
      CO(2) for 25min at 5MPa and 40 degrees C (313K) and the addition of 4ml of
      specific detergent per litre of CO(2) assures at least a five log step reduction
      of Enterobacter aerogenes and C. albicans, whilst treatment at 50 degrees C
      (323K) with CO(2) for 25min at 5MPa is sufficient for at least a five log step
      reduction for Enterococcus faecium. It was also found that a 15-min CO(2)
      treatment at 7MPa and 20 degrees C (293K) was sufficient for the inactivation of
      the yeast C. albicans, whilst these conditions were not rigorous enough for the
      challenge bacteria. On the other hand, the labscale treatment with CO(2) for
      25min at pressure 4 and 6MPa with the addition of detergent or hydrogen peroxide
      only yields a log step reduction of up to 4 log steps, thus proving the slightly
      disinfective properties of the CO(2) treatment with added agents, but not
      reaching efficient results as a 5 log step reduction was not reached.
      CONCLUSIONS: Addition of heat to the compressed CO(2) treatment of textiles
      inoculated with microorganisms proved more effective than the addition of
      detergent or disinfectant with compressed CO(2) treatment at temperature of 20
      degrees C. SIGNIFICANCE AND IMPACT OF THE STUDY: CO(2) treatment of textiles is a
      promising ecological alternative dry-cleaning method for the disinfection of
      medical textiles.

PMID- 22151329
TI  - Projections and interconnections of genetically defined serotonin neurons in
      mice.
AB  - Brain serotonin neurons are heterogeneous and can be distinguished by several
      anatomical and physiological characteristics. Toward resolving this heterogeneity
      into classes of functional relevance, subtypes of mature serotonin neurons were
      previously identified based on gene expression differences initiated during
      development in different rhombomeric (r) segments of the hindbrain. This
      redefinition of mature serotonin neuron subtypes based on the criteria of genetic
      lineage, along with the enabling genetic fate mapping tools, now allows various
      functional properties, such as axonal projections, to be allocated onto these
      identified subtypes. Furthermore, our approach uniquely enables interconnections
      between the different serotonin neuron subtypes to be determined; this is
      especially relevant because serotonin neuron activity is regulated by several
      feedback mechanisms. We used intersectional and subtractive genetic fate mapping
      tools to generate three independent lines of mice in which serotonin neurons
      arising in different rhombomeric segments, either r1, r2 or both r3 and r5, were
      uniquely distinguished from all other serotonin neurons by their expression of
      enhanced green fluorescent protein. Each of these subgroups of serotonergic
      neurons had a unique combination of forebrain projection targets. Typically more
      than one subgroup innervated an individual target area. Unique patterns of
      interconnections between the different groups of serotonin neurons were also
      observed and these pathways could subserve feedback regulatory circuits. Overall,
      the current findings suggest that activation of subsets of serotonin neurons
      could result in topographic serotonin release in the forebrain coupled with
      feedback inhibition of serotonin neurons with alternative projection targets.

PMID- 22151330
TI  - The rise and fall of breakpoint reuse depending on genome resolution.
AB  - BACKGROUND: During evolution, large-scale genome rearrangements of chromosomes
      shuffle the order of homologous genome sequences ("synteny blocks") across
      species. Some years ago, a controversy erupted in genome rearrangement studies
      over whether rearrangements recur, causing breakpoints to be reused. METHODS: We
      investigate this controversial issue using the synteny block's for human-mouse
      rat reported by Bourque et al. and a series of synteny blocks we generated using
      Mauve at resolutions ranging from coarse to very fine-scale. We conducted
      analyses to test how resolution affects the traditional measure of the breakpoint
      reuse rate. RESULTS: We found that the inversion-based breakpoint reuse rate is
      low at fine-scale synteny block resolution and that it rises and eventually falls
      as synteny block resolution decreases. By analyzing the cycle structure of the
      breakpoint graph of human-mouse-rat synteny blocks for human-mouse and comparing
      with theoretically derived distributions for random genome rearrangements, we
      showed that the implied genome rearrangements at each level of resolution become
      more "random" as synteny block resolution diminishes. At highest synteny block
      resolutions the Hannenhalli-Pevzner inversion distance deviates from the Double
      Cut and Join distance, possibly due to small-scale transpositions or simply due
      to inclusion of erroneous synteny blocks. At synteny block resolutions as coarse
      as the Bourque et al. blocks, we show the breakpoint graph cycle structure has
      already converged to the pattern expected for a random distribution of synteny
      blocks. CONCLUSIONS: The inferred breakpoint reuse rate depends on synteny block
      resolution in human-mouse genome comparisons. At fine-scale resolution, the cycle
      structure for the transformation appears less random compared to that for coarse
      resolution. Small synteny blocks may contain critical information for accurate
      reconstruction of genome rearrangement history and parameters.

PMID- 22151331
TI  - Technical performance of percutaneous and laminectomy leads analyzed by modeling.
AB  - The objective of this study was to compare the technical performance of
      laminectomy and percutaneous spinal cord stimulation leads with similar contact
      spacing by computer modeling. Monopolar and tripolar (guarded cathode)
      stimulation with both lead types in a low-thoracic spine model was simulated
      using UT-SCS software. Dorsal column and dorsal root fiber thresholds were
      calculated as well as the area of recruited fibers in the dorsal columns, the
      rostrocaudal span of recruited dorsal root fibers and the energy consumption at
      discomfort threshold. Tripolar stimulation is superior to monopolar stimulation
      in the recruitment of the dorsal columns, a percutaneous lead recruits a ~12%
      larger dorsal column area than a laminectomy lead does. This difference is
      reduced when the contact spacing of the lead models is the same. A percutaneous
      lead with significant wire impedance (140 Ohms) consumes ~115-240% more energy,
      whereas the same lead with negligible wire impedance consumes ~40-85% more
      energy. A deterioration of all performance parameters is predicted when a
      percutaneous lead is placed more dorsally in the epidural tissue. When positioned
      next to the dura mater, a percutaneous lead has a similar performance (fiber
      recruitment in the dorsal columns and the dorsal roots) as a laminectomy lead
      with similar contact spacing, but substantially higher energy consumption. The
      superior clinical performance of the laminectomy lead is most probably due to the
      difference in volume and insertion technique of the two lead types.

PMID- 22151332
TI  - Refractory insomnia in a patient with spinal cord stimulator lead migration.
AB  - This report outlines a case of refractory insomnia temporally related to
      migration of cervical spinal cord stimulator leads. To our knowledge this
      association is previously unreported. The patient had an intractable sleep
      disturbance until replacement of the leads. A brief review of insomnia and its
      complex relationship to chronic pain is presented. We hope that this case will
      stimulate further discussion and possibly bring to light new insights into spinal
      cord stimulation and insomnia and alert others to this possible clinical
      association of symptoms.

PMID- 22151333
TI  - Spinal cord stimulation for refractory angina pectoris: a shocking experience.
AB  - Spinal cord stimulation has been extensively utilized in the treatment of
      conditions including complex regional pain syndrome, ischemic limb pain, failed
      back surgery syndrome, and angina pectoris. Recognized complications include
      infection, dural tap, and electrode movement. We report the case of a patient who
      experienced a sensation of extremely enhanced stimulation in the area covered by
      the spinal cord stimulator while in the vicinity of a high-tension electricity
      substation. Full resolution of symptoms occurred when the spinal cord stimulator
      was switched off, indicating that active stimulators may be susceptible to the
      effects of external electrical fields.

PMID- 22151334
TI  - Intrathecal morphine infusion for chronic non-malignant pain: a multiple center
      retrospective survey.
AB  - Intrathecal morphine (ITM) is commonly used for the treatment of cancer pain.
      There is reluctance for its use in France to treat chronic noncancer pain. In
      order to appreciate its popularity, efficacy, dose escalation with time, and long
      term tolerance, we carried out a retrospective study in the neurosurgery
      departments of university teaching hospitals in France involved in intrathecal
      drug therapy. Only 44 patients with chronic noncancer pain used implanted pumps
      for ITM treatment. Nineteen patients were available for detailed analysis. This
      survey concerns these 19 patients. There were 13 women and six men. Their average
      age was 48.8 years (range: 30-69 y). The mean duration of pain before pump
      implantation was 100 months (range: 12-240 m). The mean follow-up since
      implantation was 54 m (range: 4-144 m). Thirteen patients were suffering from
      postsurgery lumbar and radicular pain. The average initial and final dose per day
      of morphine was 1.3 mg (range: 1-2 mg) and 2.5 mg (range: 1-6.7 mg) for patients
      with nociceptive pain and 1.2 mg (range: 0.7-2 mg) and 3 mg (range: 1-10 mg) for
      patients with mixed pain, respectively. Five (26.3%) of 19 patients returned to
      their initial jobs. Increase in activity level was reported as good in seven
      patients (36.8%). Patient satisfaction rate was 90%. The VAS rate was reduced to
      49.2% of the initial values while the subjective pain relief was estimated at
      67.8%. Two cases (10.5%) of late pump site infection and two patients (10.5%)
      with catheter displacements were recorded. Side effects imputable to morphine
      included; constipation, somnolence, decreased libido, weight gain, amenorrhoea,
      vomiting, nightmares, and itching. No development of tolerance or addiction were
      recorded. We conclude that in well selected cases ITM should be considered as a
      possible therapeutic option in the treatment of intractable chronic benign pain.

PMID- 22151335
TI  - Multiple lead spinal cord stimulation for chronic mechanical low back pain: a
      comparative study with intrathecal opioid drug delivery.
AB  - The objective of this paper is to assess the outcome of implanted multiple
      thoracolumbar lead spinal cord stimulation (SCS) in mechanical back pain without
      prior spinal surgery. These results are compared with intrathecal opioid drug
      delivery (ITDD). An anonymous third party patient questionnaire study of pain
      relief, function and psychosocial quality of life measures (recorded on 11-point
      numerical rating scales) for 12 patients with SCS and 13 with ITDD was used. Pain
      was significantly reduced with multiple lead SCS from a median of 9.0-6.5 (p <
      0.01) and with ITDD from a median of 8.5-5.5 (p < 0.01). There was a trend
      towards greater reduction in pain in the ITDD group compared with the SCS group
      (pain differences 4.5 and 2.6, respectively) but this did not reach statistical
      significance. The majority of psychosocial quality of life measures were
      significantly more improved in the ITDD group compared with the SCS group (p <
      0.05). We conclude that multiple-lead SCS improves mechanical back pain in
      patients unresponsive to more conservative measures. However, ITDD provides
      significantly more improved quality of life measures, with a trend towards
      greater pain reduction than SCS.

PMID- 22151336
TI  - Brain-Computer Interface-FES Integration: Towards a Hands-free Neuroprosthesis
      Command System.
AB  - This paper presents a critical review of brain-computer interfaces (BCIs) and
      their potential for neuroprosthetic applications. Summaries are provided for the
      command interface requirements of hand grasp, multijoint, and lower extremity
      neuroprostheses, and the characteristics of various BCIs are discussed in
      relation to these requirements. The review highlights the current limitations of
      BCIs and areas of research that need to be addressed to enhance BCI-FES
      integration.

PMID- 22151337
TI  - The sensitivity and selectivity of an implantable two-channel peroneal nerve
      stimulator system for restoration of dropped foot.
AB  - The objective of this study was to evaluate the stimulation responses on each
      channel of an implantable two-channel stimulator that stimulates the peroneal
      nerve branches innervating the muscles for dorsiflexion and eversion movements.
      Currently five Dutch patients and five English patients have been implanted with
      this system. Isometric ankle torque measurements were carried out in the patient
      with the longest follow-up period (1 y). A force sensor measured the three
      components of moment generated at the ankle joint. Stimulation intensity can be
      adjusted with great accuracy. Dorsiflexion moments are almost entirely determined
      by the setting of channel 1. Eversion moments are determined mainly by channel 2
      and to a lesser extent by channel 1. Both channels determined abduction/adduction
      moments. We conclude that stimulation responses in both dorsiflexion and eversion
      direction can be set individually and with great accuracy and are reproducible
      over a prolonged period.

PMID- 22151338
TI  - International Functional Electrical Stimulation Society (IFESS): the Development
      of Controlled Neural Prostheses for Functional Restoration.

PMID- 22151339
TI  - Reliability and clinical utility of an implanted intraspinal catheter used in the
      treatment of spasticity and pain.
AB  - Objectives. To examine the performance and reliability of a redesigned
      implantable intrathecal catheter. Materials and Methods. A total of 212 catheters
      were implanted in 202 patients in this 22-center prospective study of an
      implantable catheter/pump system used to deliver intrathecal drugs for the
      treatment of pain and spasticity. Along with physician assessments of ease of
      use, the rates of common catheter complications (dislodgments, disconnections,
      fractures, and kinks) experienced during the study were analyzed in relation to
      implant conditions (catheter entry site, tip position, and anchoring method).
      Results. A cumulative total of 3112.8 months of patient experience (average: 15.4
      months; range: 0-30.2 months per catheter) revealed an overall catheter-caused
      complication rate of 0.3% per patient month. Physician assessments were favorable
      with 89% rating this catheter as better than previously used intraspinal
      catheters. A measure of catheter survival estimates (Kaplan-Meier) at nine months
      was 89% including all complications. Comparison of data relating to implant
      techniques demonstrated a variety of catheter implant techniques (entry,
      positioning, anchoring) with no correlation between any one technique and the
      common complications. Conclusions. Performance data and physician assessments
      indicate that this catheter is an improvement over the previously available
      catheter.

PMID- 22151340
TI  - Principles of Sacral Nerve Stimulation (SNS) for the Treatment of Bladder and
      Urethral Sphincter Dysfunctions.
AB  - Objectives. Sacral nerve stimulation (SNS) (Medtronic, Inc., Minneapolis, MN) is
      an exciting new treatment for refractory voiding disorders including urinary
      incontinence, retention, and voiding dysfunction. It is known that both voiding
      and continence reflex mechanisms are organized in the sacral spinal cord and that
      pathologic conditions can alter the balance between these two opposing
      mechanisms. Methods. The background and surgical technique of SNS will be
      presented. This will be followed by a discussion of hypotheses on how SNS works.
      Results. The beneficial effects of SNS are most reasonably attributed to
      activation of somatic afferent axons in the sacral spinal roots. This evoked
      afferent activity in turn modulates sensory processing and micturition reflex
      pathways in the spinal cord. Hyperactive voiding can be suppressed by direct
      inhibition of bladder preganglionic neurons as well as inhibition of
      interneuroneal transmission in the afferent limb of the micturition reflex. On
      the other hand, voiding in patients with urinary retention can be facilitated by
      inhibition of reflex pathways to the urethral outlet (guarding reflexes).
      Conclusions. SNS, a nonablative, minimally invasive technique for urologists,
      holds great promise for a large number of patients who suffer debilitating and
      refractory urinary symptoms.

PMID- 22151342
TI  - N = 1: Let's Not Forget the Individual Patient.

PMID- 22151341
TI  - Hardware failures in spinal cord stimulation for failed back surgery syndrome.
AB  - Spinal cord stimulation (SCS) is an efficient means for treatment of the
      postsurgical lumbar spine condition known as failed back surgery syndrome (FBSS).
      Although the devices and the implantation techniques are well established and the
      technology is sophisticated, there are some complications caused by hardware
      failures. This study was aimed at identifying the most frequent types of hardware
      failures and their causes in FBSS patients treated with SCS. In a retrospective
      analysis, a group of 42 FBSS patients using single lead SCS for 6-74 months was
      evaluated. Only hardware failures were considered in the analysis, and parameters
      such as occurrence of failure after primary implantation of the device, frequency
      and site of failure, stimulation time to failure (TF), and overall time of SCS
      usage were recorded. In the patient group studied, 12 surgical corrections of the
      hardware were carried out in 10 patients. In eight patients there was a single
      corrective procedure, in two additional cases there were two surgically corrected
      hardware failures each. The most often encountered type of hardware failure was
      lead breakage or disruption of insulation (percutaneously placed Quad leads only)
      leading to short circuiting and dysfunction (n= 8). Second in frequency were
      receiver (model 3470) failures due to insulation leakage at the plug connection
      site (n= 2). In one case, extension cable breakage caused dysfunction of the
      system, and another dysfunction was caused by distal extension cable
      disconnection. In conclusion, SCS is a low-complication procedure for treatment
      of benign low-back pain, but seems to be prone to lead and insulation failures.

PMID- 22151343
TI  - Integrating sensory nerve signals into neural prosthesis devices.
AB  - Electrical signals can be recorded using long-term implanted nerve cuff
      electrodes in human peripheral nerves. Reliable detection of sensory nerve
      signals is essential if such signals are to be of use in sensory-based functional
      electrical stimulation neural prosthetics as a replacement for artificial sensors
      (switches, strain gauges, etc.). In this review, the signal characteristics of
      the sensors, the nerve interface, signal processing, and an example of human
      application to restore motor functions are described.

PMID- 22151344
TI  - Effect of intertrial delay on whole nerve cuff recordings of muscle afferents in
      rabbits.
AB  - Objective. The effect of the stationary period on the muscle afferent
      responsiveness to passive stretch was studied to determine if muscle afferent
      activity might be suitable as feedback in motor-neural prostheses control.
      Methods. Muscle afferent activity was recorded using nerve cuff electrodes
      applied individually to the tibial and peroneal components of the sciatic nerve
      in five rabbit preparations. The ankle joint was rotated using a servomotor. The
      delay between trapezoidal movements was varied (excursion = 30 degrees , velocity
      = 20 degrees /s) and the duration was increased stepwise in successive trials(2
      s, 5 s, 10 s, 20 s, 30 s, and 180 s). Results. An increase in amplitude of the
      afferent activity with increasing intertrial delay was observed. The afferent
      responses following a 2-s delay were subtracted from the responses following each
      of the remaining intervals (5 s-2 s, 10 s-2 s, 20 s-2 s, 30 s-2 s and 180 s-2 s)
      and were then compared. During the ramp phase a statistically significant
      difference was found in 85% and 76% of the cases for the tibial and peroneal
      nerve responses. Significant differences were below 21% for both nerves during
      four other phases examined. Conclusions. It is suggested that the enhancement in
      afferent responses caused by the increased intertrial delay may be explained by
      the change in the mechanical properties of the intrafusal and extrafusal muscle
      fibers. The consequences of this, when applying muscle afferent activity in motor
      neuro prostheses, are discussed.

PMID- 22151345
TI  - A retrospective comparison of surgical removal and subsequent CO2 laser ablation
      versus topical administration of mitomycin C as therapy for equine corneolimbal
      squamous cell carcinoma.
AB  - OBJECTIVE:   To compare the complications and nonrecurrence rate following
      topical mitomycin C (MMC) therapy vs. CO(2) laser ablation for treating equine
      corneolimbal squamous cell carcinoma (SCC). STUDY DESIGN:   Retrospective study.
      SAMPLE POPULATION:   Twenty-five horses with corneolimbal SCC. PROCEDURES:  
      Medical records of horses undergoing surgical tumor resection followed by either
      topical MMC therapy (0.04%) or CO(2) laser ablation between the years of 2004 and
      2010 were reviewed. Recurrence and complications were compared between groups and
      within MMC subgroups defined by the time at which treatment was initiated
      relative to surgery. RESULTS:   Therapy with topical MMC resulted in a
      nonrecurrence rate comparable to that achieved with CO(2) laser ablation (82.4%
      vs. 85.7%, respectively). Initiation of MMC following epithelialization of the
      surgical site a mean of 15 days postoperatively did not result in increased
      recurrence rates relative to treatment in the immediate postoperative period.
      Vision- or globe-threatening complications tended to occur with greater frequency
      in horses receiving topical MMC in the immediate postoperative period (5 of 6
      major complications) relative to following epithelialization of the surgical site
      (1 of 6 major complications). CONCLUSIONS:   Horses receiving adjunctive topical
      MMC therapy were no more likely to experience tumor recurrence than were horses
      undergoing CO(2) laser ablation in the horses in this study. Initiation of two to
      three rounds of MMC following epithelialization of the surgical site results in
      fewer major complications and achieves comparable disease resolution relative to
      treatment in the immediate postoperative period.

PMID- 22151346
TI  - Completeness and timeliness of tuberculosis notification in Taiwan.
AB  - Tuberculosis (TB) is a notifiable disease by the Communicable Disease Control Law
      in Taiwan. Several measures have been undertaken to improve reporting of TB but
      the completeness and timeliness of TB notification in Taiwan has not yet been
      systemically evaluated. METHODS: To assess completeness and timeliness of TB
      notification, potential TB cases diagnosed by health care facilities in the year
      2005-2007 were identified using the reimbursement database of national health
      insurance (NHI), which has 99% population coverage in Taiwan. Potential TB
      patients required notification were defined as those who have TB-related ICD-9
      codes (010-018) in the NHI reimbursement database in 2005-2007, who were not
      diagnosed with TB in previous year, and who have been prescribed with 2 or more
      types of anti-TB drugs. Each potential TB case was matched to the national TB
      registry maintained at Taiwan Centers for Disease Control (CDC) by using national
      identity number or, if non-citizen, passport number to determine whether the
      patients had been notified to local public health authorities and Taiwan CDC. The
      difference in the number of days between date of anti-tuberculosis treatment and
      date of notification was calculated to determine the timeliness of TB reporting.
      RESULTS: Of the 57,405 TB patients who were prescribed with 2 or more anti
      tuberculosis drugs, 55,291 (96.3%) were notified to National TB Registry and
      2,114 (3.7%) were not. Of the 55,291 notified cases, 45,250 (81.8%) were notified
      within 7 days of anti-tuberculosis treatment (timely reporting) and 10,041(18.2%)
      after 7 days (delayed reporting). Factors significantly associated with failure
      of notification are younger age, previously notified cases, foreigner, those who
      visited clinics and those who visited health care facilities only once or twice
      in 6 months. CONCLUSION: A small proportion of TB cases were not notified and a
      substantial proportion of notified TB cases had delayed reporting, findings with
      implication for strengthening surveillance of tuberculosis in Taiwan. Countries
      where the completeness and timeliness of TB notification has not yet been
      evaluated should take similar action to strengthen surveillance of TB.

PMID- 22151347
TI  - Learning from estrogen receptor antagonism: structure-based identification of
      novel antiandrogens effective against multiple clinically relevant androgen
      receptor mutants.
AB  - Current treatment strategy for advanced prostate cancer is to suppress androgen
      receptor (AR) by castration and antiandrogens. However, several clinically
      relevant AR mutations cause insensitivity to current antiandrogens and convert
      them into agonists. We aim to identify full AR antagonists even for AR mutants.
      As crystal structure of AR ligand-binding domain (LBD) at antagonistic form is
      not available, we decided to learn from estrogen receptor (ER) antagonism: (i) We
      built a structural model of wild-type AR-LBD complexed with antiandrogen
      bicalutamide (wild type/bicalutamide) using ERalpha-LBD/hydroxytamoxifen
      structure as the template for helix-12. (ii) By comparative structural analysis
      of 24 ERalpha-LBD complexes, we found residues D351 and L354 at helix-3 adopt
      unique conformations, and distance between them is a marker of ERalpha
      LBD/antagonist complexes. The AR residues corresponding to D351 and L354 are E709
      and L712, respectively. We found distance between E709 and L712 of the wild
      type/bicalutamide model is substantially different from that of AR-LBD/agonist
      complexes, suggesting this distance could be a marker of antagonistic AR-LBD,
      which was supported by molecular dynamics simulations. Based on the wild
      type/bicalutamide model, we discovered compound 3 is a novel antiandrogen
      effective against the wild type and T877A-, W741C-, and H874Y-mutated androgen
      receptors. We found compound 3 has dual functions, inhibiting androgen receptor
      and IKK(beta) .

PMID- 22151348
TI  - Mammographic screening practices among Chinese-Australian women.
AB  - PURPOSE: To report mammographic screening practice among Chinese-Australian
      women, and to examine the relationship between demographic characteristics,
      acculturation factors (English proficiency and length of stay in Australia),
      cultural beliefs, and having a mammogram as recommended. DESIGN: Cross-sectional
      and descriptive. The study was conducted in 2009 in Sydney, Australia. Of 988
      Chinese-Australian women over 18 years of age invited to participate in the
      study, 785 (79%) completed and returned the questionnaire. Of these women, 320
      (40.8%) were in the target age range of 50 to 69 years. METHODS: The Chinese
      Breast Cancer Screening Beliefs Questionnaire (CBCSB) was used as a data
      collection instrument. Analysis included descriptive statistics, bivariate
      analysis using chi-square and t tests, and logistic regression. RESULTS: Of the
      320 women in the targeted age range of 50 to 69 years, 238 (74.4%) had a
      mammogram as recommended biannually. Being married-de facto, in the 60 to 69 age
      group, and speaking Cantonese at home were positively associated with women's
      mammographic screening practice. However, no statistically significant
      differences in acculturation factors and having a mammogram as recommended were
      found. In terms of CBCSB score, women who had mammograms as recommended had more
      positive attitudes toward health checkups and perceived fewer barriers to
      mammographic screening. CONCLUSIONS: Effort should be focused on specific
      subgroups of Chinese-Australian women in order to fully understand the barriers
      involved in participating in mammographic screening. CLINICAL RELEVANCE: Nurses
      can use the findings from the present study to design culturally sensitive breast
      cancer screening programs to encourage women's participation in mammography.

PMID- 22151349
TI  - Identification of telocytes in the upper lamina propria of the human urinary
      tract.
AB  - The upper lamina propria (ULP) area of interstitial cells (IC) has been studied
      extensively in bladder, but is rather unexplored in the rest of the urinary
      tract. This cell layer is intriguing because of the localization directly
      underneath the urothelium, the intercellular contacts and the close relationship
      with nerve endings and capillaries. In this study, we examine the ULP layer of IC
      in human renal pelvis, ureter and urethra, and we make a comparison with ULP IC
      in bladder. Tissue was obtained from normal areas in nephrectomy, cystectomy and
      prostatectomy specimens, and processed for morphology, immunohistochemistry and
      electron microscopy. A morphological and immunohistochemical phenotype for the
      ULP IC was assessed and region-dependent differences were looked for. The ULP IC
      in renal pelvis, ureter and urethra had a similar ultrastructural phenotype,
      which differed somehow from that of bladder IC, that is, thinner and longer
      cytoplasmic processes, no peripheral actin filaments and presence of dense core
      granules and microtubules. Together with their immunohistochemical profile, these
      features are most compatible with the phenotype of telocytes, a recently
      discovered group of stromal cells. Based on their global ultrastructural and
      immunohistochemical phenotype, ULP IC in human bladder should also be classified
      as telocytes. The most striking immunohistochemical finding was the variable
      expression of oestrogen receptor (ER) and progesterone receptor (PR). The
      functional relevance of ULP telocytes in the urinary tract remains to be
      elucidated, and ER and PR might therefore be promising pharmacological research
      targets.

PMID- 22151350
TI  - An update review on risk factors and scales for prediction of deep sternal wound
      infections.
AB  - Surgical site infections are the most common nosocomial infections in surgical
      patients. The preventable and the unmodifiable risk factors for deep sternal
      wound infections (DSWI) have been amply assessed in the literature. The aim of
      this review was to describe the results of the numerous published studies to
      describe all the DSWI risk factors and the scales devised to predict SWI, with a
      view to providing an update on this issue. A comprehensive search of the Medline
      and Embase databases was performed (considering studies from January 1995 to
      April 2011); and a manual search was also conducted using references cited in
      original publications and relevant review articles. There are several risk
      factors associated with DSWI, which could be classified in four categories as
      demographic (e.g. sex and age), behavioural (e.g. smoking and obesity), baseline
      clinical conditions (e.g. diabetes, hypertension and COPD) and surgical operative
      risk factors (e.g. duration of operation and emergency operation). Six scales for
      predicting the risk of DSWI are described in the literature: they vary not only
      in accuracy but also in ease of application and they are applied at different
      times (some only preoperatively and others also postoperatively). This study
      provides a broad update on our knowledge of the risk factors for DSWI and the
      scales for prediction with a view to improving the management of infections at
      cardiosurgery units.

PMID- 22151352
TI  - Roles of quaternary structure and cysteine residues in the activity of human
      serine racemase.
AB  - BACKGROUND: D-serine is an important coagonist at the NR1 subunit of the NMDA
      receptor class of glutamate receptors. It is chiefly synthesized in the CNS by
      serine racemase (SR). Regulation of SR activity is still poorly understood. As
      step toward developing reagents and methods for investigating SR in vitro, we
      analyzed structure-function relationships of a recombinant enzyme of human
      sequence. RESULTS: Michaelis-Menten kinetic analysis indicated a KM value of 14
      mM and Vmax value of 3.66 MUmol.mg-1.hr-1 when L-serine was used as a substrate
      for purified SR. Gel-filtration chromatography and protein cross-linking
      experiments revealed that dimer is the major oligomeric form of recombinant SR in
      aqueous solution, though the proportions of monomer, tetramer, and larger
      aggregates differed somewhat with the specific buffer used. These buffers also
      altered activity in a manner correlating with the relative abundance of dimer.
      Activity assays showed that the dimeric gel-filtration fraction held the highest
      activity. Chemical reduction with DTT increased the activity of SR by elevating
      Vmax; cystamine, a reagent that blocks sulfhydryl groups, abolished SR activity.
      Gel-filtration chromatography and western blot analysis indicated that DTT
      enhanced the recovery of noncovalent SR dimer. CONCLUSIONS: These data suggest
      that SR is most active as a noncovalent dimer containing one or more free
      sulfhydryls in the enzyme's active center or a modulatory site. Buffer
      composition and reduction/oxidation status during preparation can dramatically
      impact interpretations of SR activity. These findings also highlight the
      possibility that SR is sensitive to oxidative stress in vivo.

PMID- 22151351
TI  - Basic fibroblast growth factor inhibits osteogenic differentiation of stem cells
      from human exfoliated deciduous teeth through ERK signaling.
AB  - OBJECTIVE: Stem cells from human exfoliated deciduous teeth (SHED) are a unique
      postnatal stem cell population capable of regenerating mineralized tissue and
      treating immune disorders. However, the mechanism that controls SHED
      differentiation is not fully understood. Here, we showed that basic fibroblast
      growth factor (bFGF) treatment attenuated SHED-mediated mineralized tissue
      regeneration through activation of the extracellular signal-regulated kinase
      (ERK) 1/2 pathway. MATERIAL AND METHOD: The level of mineralized nodule formation
      was assessed by alizarin red staining. Expression levels of osteogenic genes,
      osteocalcin and runt-related transcription factor 2, were examined by RT-PCR.
      Subcutaneous implantation approach was used to assess in vivo bone formation.
      Downstream signaling pathways of bFGF were examined by Western blotting. RESULT:
      Activation of ERK1/2 signaling by bFGF treatment inhibited WNT/beta-catenin
      pathway, leading to osteogenic deficiency of SHED. ERK1/2 inhibitor treatment
      rescued bFGF-induced osteogenic differentiation deficiency. CONCLUSION: These
      data suggest that bFGF inhibits osteogenic differentiation of SHED via ERK1/2
      pathway. Blockade ERK1/2 signaling by small molecular inhibitor treatment
      improves bone formation of SHED after bFGF treatment.

PMID- 22151353
TI  - Belatacept: from rational design to clinical application.
AB  - Gradually improved immunosuppression has contributed significantly to the
      progress achieved in transplantation medicine so far. Nevertheless, current drug
      regimens are associated with late graft loss--in particular as a result of
      immunologic damage or drug toxicity--and substantial morbidity. Recently, the
      costimulation blocker belatacept (marketed under the name Nulojix(r)) has been
      approved for immunosuppression in renal transplantation. Belatacept (a mutated
      version of CTLA4Ig) is a fusion protein rationally designed to block CD28, a
      critical activating receptor on T cells, by binding and saturating its ligands B7
      1 and B7-2. In phase II and III trials, belatacept was compared with cyclosporine
      (in combination with basiliximab, MMF, and steroids). Advantages observed with
      belatacept include superior graft function, preservation of renal structure and
      improved cardiovascular risk profile. Concerns associated with belatacept are a
      higher frequency of cellular rejection episodes and more post-transplant
      lymphoproliferative disorder (PTLD) cases especially in EBV seronegative
      patients, who should be excluded from belatacept-based regimens. Thus, after
      almost three decades of calcineurin inhibitors as mainstay of immunosuppression,
      belatacept offers a potential alternative. In this article, we will provide an
      overview of belatacept's preclinical development and will discuss the available
      evidence from clinical trials.

PMID- 22151354
TI  - Evaluation of job satisfaction of practice staff and general practitioners: an
      exploratory study.
AB  - BACKGROUND: Primary care teams' job satisfaction is an important issue in quality
      of care. The purpose of our study was to evaluate the job satisfaction of general
      practitioners (GPs) and non-physician staff and to explore the elements that may
      impact on overall job satisfaction for GPs and non-physician staff separately.
      METHODS: The study was based on data from the European Practice Assessment and
      used an observational design. Job satisfaction was measured with the 10-items
      Warr-Cook-Wall questionnaire with 7-point-Likert scales. Job satisfaction of GPs
      and non-physician staff was compared and impact on overall job satisfaction was
      analysed with stepwise linear regression analyses for both samples separately.
      RESULTS: The study population consisted of 2878 non-physician staff (mean age: 38
      years) and 676 GPs (mean age: 50 years). The actual mean working time per week of
      GPs was 50.0 hours and of practice staff 26.0 hours. Both were satisfied with
      colleagues and fellow workers (mean = 5.99 and mean = 6.18 respectively) and
      mostly dissatisfied with their income (mean = 4.40 and mean = 4.79 respectively).
      For GPs the opportunity to use their abilities (beta = 0.638) and for non
      physician staff recognition for their work (beta = 0.691) showed the highest
      scores of explained variance (R2 = 0.406 and R2 = 0.477 respectively) regarding
      overall job satisfaction. CONCLUSIONS: Non-physician staff evaluate their job
      satisfaction higher than GPs except recognition for work. Job satisfaction of
      members of primary care teams is important because poor satisfaction is
      associated with suboptimal healthcare delivery, poor clinical outcomes and higher
      turnover of staff.

PMID- 22151355
TI  - Contribution of physical education to overall physical activity.
AB  - For many children, physical activity (PA) during physical education (PE) lessons
      provides an important opportunity for being physically active. Although PA during
      PE has been shown to be low, little is known about the contribution of PA during
      PE to overall PA. The aim was therefore to assess children's PA during PE and to
      determine the contribution of PE to overall PA with special focus on overweight
      children. Accelerometer measurements were done in 676 children (9.3 +/- 2.1
      years) over 4-7 days in 59 randomly selected classes. Moderate-and-vigorous PA
      (MVPA; >= 2000 counts/min) during PE (MVPAPE), overall MVPA per day (MVPADAY),
      and a comparison of days with and without PE were calculated by a regression
      model with gender, grade, and weight status (normal vs overweight) as fixed
      factors and class as a random factor. Children spent 32.8 +/- 15.1% of PE time in
      MVPA. Weight status was not associated to MVPAPE . MVPAPE accounted for 16.8 +/-
      8.5% of MVPADAY, and 17.5 +/- 8.2% in overweight children. All children were more
      active on days with PE than on days without PE (differences: 16.1 +/- 29.0 min of
      MVPADAY; P <= 0.001; 13.7 +/- 28.0 min for overweight children). Although MVPAPE
      was low, PE played a considerable role in providing PA and was not compensated by
      reducing extracurricular MVPA.

PMID- 22151356
TI  - Heart rate, heart rate variability, and arrhythmias in dogs with myxomatous
      mitral valve disease.
AB  - BACKGROUND: Autonomic modulation of heart rhythm is thought to influence the
      pathophysiology of myxomatous mitral valve disease (MMVD). HYPOTHESES: (1) Holter
      derived variables reflecting autonomic modulation of heart rhythm change with
      MMVD severity in Cavalier King Charles Spaniels (CKCS); (2) Holter-derived
      variables can identify MMVD severity in CKCS; and (3) Holter-derived variables in
      CKCS in congestive heart failure (CHF) secondary to MMVD differ from those in
      dogs of other breeds in CHF. ANIMALS: Ninety privately owned dogs: 70 CKCS with
      variable MMVD severity and 20 non-CKCS in CHF secondary to MMVD. METHODS: Dogs
      were prospectively recruited and divided into 5 MMVD severity groups based on
      history, breed, and physical and echocardiographic examination findings. Holter
      derived variables included heart rate variability (HRV), heart rate (HR), and
      arrhythmia evaluated from 24-hour Holter recordings. RESULTS: In CKCS, 18 of 26
      HRV (all P < .0002) and 3 of 9 arrhythmia (all P < .0004) variables decreased
      with increasing MMVD, whereas minimum and mean HR (all P < .0001) increased with
      increasing MMVD severity. An arrhythmia variable representing sinus arrhythmia
      ("premature normals") (P < .0001) and the HRV variable triangular index (TI) (P <
      .0001) could distinguish CKCS with moderate or severe mitral regurgitation from
      CKCS in CHF in specific intervals. Among dogs in CHF, Holter-derived variables
      did not differ among breeds. CONCLUSIONS AND CLINICAL IMPORTANCE: In CKCS, Holter
      derived variables changed with MMVD severity. "Premature normals" and TI showed
      diagnostic potential. Breed differences were not seen among dogs in CHF secondary
      to MMVD.

PMID- 22151357
TI  - NANS Training Requirements for Spinal Cord Stimulation Devices: Selection,
      Implantation, and Follow-up.

PMID- 22151358
TI  - Neuromodulation of the pudendal, hypogastric, and tibial nerves with pelvic floor
      muscle rehabilitation in the treatment of urinary urge incontinence.
AB  - Objectives. The hypothesis of the study is that adding percutaneous tibial nerve
      neuromodulation (Urgent PC, Uroplasty Inc., Minneapolis, MN, USA) with pelvic
      floor muscle rehabilitation (Evadri System, Hollister Inc., Libertyville, IL,
      USA) is safe, and more successful than either therapy alone for the treatment of
      urge incontinence. Material and Methods. Two hundred and fifty-six female
      patients with urge incontinence or mixed incontinence were included in this
      investigation. Patients were treated sequentially (on the same day) with both
      pelvic floor muscle rehabilitation and percutaneous tibial nerve neuromodulation
      twice per week at the Southern Arizona Urogynecology Center, Tucson, Arizona.
      Results. At three months 93% of the patients were dry. The remaining 7% of
      patients had a mean improvement of 84% in their incontinence episodes. The median
      follow-up is now 19 months. There were no adverse side events. Conclusions.
      Neuromodulation of the pudendal, hypogastric, and tibial nerves is a highly
      effective treatment for urge incontinence, and superior to either treatment alone
      by a factor of greater than two times (see Table 1). [Table: see text].

PMID- 22151359
TI  - Functional electrical stimulation control of standing and stepping after spinal
      cord injury: a review of technical characteristics.
AB  - Objectives. To investigate the different approaches in the field of functional
      electrical stimulation (FES) control of gait and address fundamental perquisites
      to enable FES walking systems to become safer, more practical, and therefore
      clinically efficacious. Design. Systematic review was conducted from electronic
      data bases up to March 2008. Studies with innovative control strategies were
      highlighted for analysis, but all relevant literatures were described to deliver
      a broad viewpoint. Study Selection. FES studies applying 1) open and closed-loop
      controllers; 2) control algorithm techniques; or 3) feedback information to the
      control unit of neuromuscular stimulators via biological signals or artificial
      sensors. These studies were mostly associated to FES gait. Results. By far, more
      spinal cord-injured users have benefited from open-loop FES walking systems
      because they have had an easier and faster setup. However, because of their
      limitations over the control of knee extension, closed-loop control of gait may
      be a superior approach. The use of electromyogram to quantify quadriceps fatigue
      was not considered sufficiently appropriate to predict knee-buckle events;
      instead, the use of motion sensors for such purposes is recommended. Finite state
      controllers based on a set of deterministic rules to process feedback signals
      seemed more suitable to provide accurate command-and-control compared with
      dynamic or neural network controllers. Conclusions. Progress in the development
      of closed-loop FES walking systems has been impeded by their lack of
      practicality. In the near future, this obstacle could be overcome via implanted
      systems, especially if using controllers based on deterministic rule sets derived
      from motion sensor feedback.

PMID- 22151360
TI  - The deep brain stimulation of the pedunculopontine tegmental nucleus.
AB  - Objective. The aim of the present study was to describe the surgical and clinical
      outcomes of the implantation and stimulation of the pedunculopontine tegmental
      nucleus in humans. Materials and Methods. Fourteen patients affected by movement
      disorders (12 Parkinson's disease and 2 progressive supranuclear palsy) underwent
      surgery for bilateral or monolateral implantation of stimulating electrodes in
      the pedunculopontine tegmental nucleus. The correct placement of electrodes was
      established and verified by combining angio-CT scans with magnetic resonance
      imaging. Intraoperative and postoperative evaluations were made to assess the
      clinical effectiveness of stimulation according to different Unified Parkinson's
      Disease Rating Scale items and neurophysiologic parameters. Results. No major
      complications occurred following the insertion of electrodes into the
      pedunculopontine tegmental nucleus. Neuroimaging showed that the electrode
      contacts were always correctly placed below the ponto-mesencephalic line.
      Stimulation of the pedunculopontine tegmental nucleus improved gait, posture, and
      speech, and modulated reflexes integrated at spinal or pontine levels.
      Conclusions. The surgical targeting of the pedunculopontine tegmental nucleus
      requires a careful adaptation of the traditional stereotactic approaches owing to
      the high variability of brainstem anatomy from one patient to another. The
      insertion of the leads in the pedunculopontine tegmental nucleus as well as their
      activation did not appear to induce serious adverse effects. The correct
      positioning of stimulating electrodes in pontine structures such as the
      pedunculopontine nucleus may be ascertained not only through neuroimaging
      techniques but also through clinical neurophysiology. The evolution of the
      surgical planning that we have developed emphasizes the limited value of single
      unit recordings to identify the pedunculopontine tegmental nucleus and highlights
      the opportunities offered by functional evaluations of neurophysiologic
      parameters. As far as the clinical efficacy is concerned, our data suggest a
      promising outcome for simultaneous implantations of different basal ganglia
      nuclei in Parkinsonian and in progressive supranuclear palsy patients as well.

PMID- 22151361
TI  - Subcutaneous peripheral nerve stimulation with paddle lead for treatment of low
      back pain: case report.
AB  - Introduction. Peripheral nerve stimulation has become a useful tool in
      neuromodulation in the treatment of chronic and intractable pain syndromes.
      Method. While most of the reports in the literature describe the use of a
      subcutaneously placed small diameter cylindric lead, we present a case report of
      a 37-year-old man who did not have adequate axial back stimulation with such a
      lead. Conclusion. He had excellent stimulation and reduction of his pain after
      the device was replaced with an insulated subcutaneous paddle lead.

PMID- 22151362
TI  - Successful treatment of chronic neuropathic pain with subcutaneous peripheral
      nerve stimulation: four case reports.
AB  - Introduction. Chronic pain is a prevalent medical condition in the general
      population and is one of the most common reasons patients visit their primary
      care doctors. When the pain is resistant to the common treatment modalities, it
      presents a challenge for the physician and may have profound consequences for the
      quality of life of the patient. Methods. We present four case reports in which
      subcutaneous peripheral nerve stimulation was successfully used to treat chronic
      neuropathic pain after all other treatment efforts had failed. Results. In all
      cases, the patients underwent a trial of peripheral nerve stimulation with good
      results. The patients reported decreased use of pain medications, increased
      quality of life, and high satisfaction with the procedure results. Conclusion.
      The use of subcutaneous peripheral nerve stimulation as a viable treatment
      alternative in certain cases of chronic neuropathic pain should continue to be
      rigorously evaluated.

PMID- 22151363
TI  - Ultrasound-Guided Localization of Difficult-to-Access Refill Port of the
      Intrathecal Pump Reservoir.
AB  - Introduction. Ultrasound guidance is being increasingly utilized in many chronic
      pain interventions. This is a report of the use of ultrasound imaging for
      accessing an intrathecal pump. Case Report. A 56-year-old patient with a
      programmable implanted intrathecal drug delivery system for chronic non-malignant
      pain needed a pump refill of sufentanil. Attempts to access the refill port using
      the manufacturer supplied template were difficult because of the presence of a
      seroma. Using ultrasound guidance, the seroma, reservoir, and the refill port
      were visualized and the pump was successfully accessed. This imaging-guided
      refill technique is fully described in this article. As the patient continued to
      have a collection of fluid during his following visit, the collection was
      aspirated under ultrasound guidance. The specimen revealed a proteinaceous
      collection with minimal quantities of sufentanil. Conclusion. This is a
      successful demonstration of ultrasound guidance to facilitate access to a
      difficult-to-access refill port of a pump reservoir secondary to the formation of
      a seroma.

PMID- 22151364
TI  - The Glass Half Empty or Half Full-How Effective Are Long-Term Intrathecal Opioids
      in Post-herpetic Neuralgia? A Case Series and Review of the Literature.
AB  - Objectives. Post-herpetic neuralgia (PHN) is a painful complication of herpes
      zoster infection and a common cause of chronic severe pain in elderly and/or
      debilitated patients. Although a wide range of treatments have been tried, a
      substantial number of patients continue to experience pain which remains
      refractory to all therapies. Increasingly, studies have demonstrated that oral
      opioids can have a beneficial effect on neuropathic pain. However, to date, few
      studies have examined the potential benefit(s) of chronic intrathecal opioids in
      the treatment of PHN. Methods. Long-term outcome results of four PHN patients who
      had a successful intrathecal opioid trial and underwent implantation of an
      intrathecal opioid pump were examined. Data were analyzed using univariate
      analysis of variance. Results. Duration of continuous intrathecal opioid therapy
      ranged from five to 50 months and mean pain reduction was 41% (range 27-50%) as
      measured by a verbal pain score (0-100), with the greatest benefit noticed
      earlier in therapy. Mean 24-hour intrathecal morphine dose was 2.29 mg (range
      0.78-3.94 mg). Intrathecal therapy was discontinued in two patients because of
      opioid side-effects, depression, and loss of efficacy. Revision surgery was
      required in two cases. Patients most commonly reported improvement in the deep
      component of their pain, next allodynia, and less so superficial lancinating
      pain. Conclusions. In conclusion, while a complex therapy, long-term use of
      intrathecal opioids is well tolerated, doses are titratable, administration is
      safe, and may help relieve severe short- and long-term neuropathic pain in
      selected PHN patients. Whether the addition of newer investigational intrathecal
      agents could improve these results is yet to be determined.

PMID- 22151365
TI  - Functional electrical stimulation-supported interval training following
      sensorimotor-complete spinal cord injury: a case series.
AB  - Objective. To investigate the effect of interval training supported by Functional
      Electrical Stimulation (FES) on ambulation ability in complete spinal cord injury
      (SCI). Methods. We trained four men with sensorimotor-complete (ASIA A) SCI, who
      achieved gait through FES of the quadriceps femoris, gluteus maximus, and common
      peroneal nerve on each side on a motorized treadmill. Training involved
      progressive interval walking exercise, consisting of periods of activity followed
      by equal periods of rest, repeated until muscle fatigue. We used time to muscle
      fatigue during continuous treadmill ambulation as the primary outcome measure. We
      also recorded the patterns of incremental stimulation for all training and
      testing sessions. Results. All subjects increased their ambulation capacity;
      however, the responses varied from subject to subject. Some subjects increased
      the total distance walked by as much as 300% with progressive improvement over
      the entire training period; however, others made more modest gains and appeared
      to reach a performance plateau within a few training sessions. Conclusions. FES
      supported interval training offers a useful and effective strategy for strength
      endurance improvement in the large muscle groups of the lower limb in motor
      complete SCI. We believe that this training protocol offers a viable alternative
      to that of continuous walking training in people with SCI using FES to aid
      ambulation.

PMID- 22151366
TI  - Spinal cord stimulation: a 20-year retrospective analysis in 260 patients.
AB  - Introduction. Spinal cord stimulation (SCS) is used clinically by many pain
      physicians and neurosurgeons alike without regard to their own outcome data.
      Methods. We reviewed our 20-year experience retrospectively of patients receiving
      SCS implants and analyzed our data by pain type and group. Results. We present
      260 patients, 140 men and 120 women. The most frequent type of pain in our series
      was neuropathic pain in 44.25% and the most frequent diagnosis was peripheral
      vascular disease (PVD) with 98 cases. The second was failed back surgery syndrome
      (FBSS) with 65 cases and the third was complex regional pain syndrome type I
      (CRPS I), with 40 cases. In CRPS group, the mean visual analog scale (VAS) of
      this group was 77.89 +/- 13.38. In total, 5% had no pain relief, 40% had poor
      pain relief, 47.5% had good pain relief, and 7.5% had excellent pain relief. In
      FBSS group, the mean VAS was 79.62 +/- 11.69 mm. A total of 13.80% had no pain
      relief at all, 35.39% had poor pain relief, 50.76% had good pain relief, and
      there were no patients in this group who had complete pain relief. A total of 98
      patients, 78 men and 20 women, were diagnosed with PVD. The mean VAS of this
      group was 69.75 +/- 14.36 mm. A total of 11.22% had poor pain relief, 87.75% had
      good pain relief. One patient had complete pain relief and all patients in this
      group perceived at least some improvement in their symptoms. The rate of
      complications was close to 28% in our overall sample. Conclusions. In conclusion,
      we demonstrated the utility over time of this type of treatment is comparable
      with other series of efficacy of SCS. The analgesic efficacy was close to 65% in
      the overall group. The therapy was not free of complications. The preponderance
      of our patients was patients with the diagnosis of PVD and our results in this
      group of patients were excellent. These excellent results of more than 90%
      improvement suggest to us that SCS be considered as a first-line approach to the
      clinical management of patients with pain and ulcer of PVD.

PMID- 22151367
TI  - Spinal Cord Stimulation and Thalamic Pain: Long-term Results of Eight Cases.
AB  - Objectives. We submit a retrospective analysis of results of eight patients
      suffering from intractable pain of established or suspected thalamic origin.
      These patients were treated with spinal cord stimulation (SCS) in the cervical or
      dorsal cord. No patient was suffering pain from a complete hemibody or facial
      area. Material and Methods. Five men and three women aged 27-67 years were
      treated in the Pain Unit of our institution between April 1993 and January 2006.
      The cause of pain in five cases was stroke (plus one suspected). Multiple
      sclerosis was responsible for pain in two cases. An upper or lower extremity was
      affected in six cases. Extension to adjacent trunk was common. Exclusive trunk
      pain was treated in two cases. Results. The follow-up period was 36-149 months.
      Two patients were not battery-implanted because pain relief was insufficient
      during the trial phase. Two patients had a further stroke: One died and one was
      cured from pain. Good-to-excellent results were attained in six patients; long
      term good-to-excellent results were maintained in three patients. Conclusions.
      Despite previous adverse reports, certain cases of thalamic pain can be
      effectively alleviated through SCS.

PMID- 22151368
TI  - Electromagnetic navigation technology for more precise electrode placement in the
      foramen ovale: a technical report.
AB  - Introduction. Interventional pain management techniques require precise
      positioning of needles or electrodes, therefore fluoroscopic control is
      mandatory. This imaging technique does however not visualize soft tissues such as
      blood vessels. Moreover, patient and physician are exposed to a considerable dose
      of radiation. Computed tomography (CT)-scans give a better view of soft tissues,
      but there use requires presence of a radiologist and has proven to be laborious
      and time consuming. Objectives. This study is to develop a technique using
      electromagnetic (EM) navigation as a guidance technique for interventional pain
      management, using CT and/or magnetic resonance (MRI) images uploaded on the
      navigation station. Methods. One of the best documented interventional procedures
      for the management of trigeminal neuralgia is percutaneous radiofrequency
      treatment of the Gasserian ganglion. EM navigation software for intracranial
      applications already exists. We developed a technique using a stylet with two
      magnetic coils suitable for EM navigation. The procedure is followed in real time
      on a computer screen where the patient's multislice CT-scan images and three
      dimensional reconstruction of his face are uploaded. Virtual landmarks on the
      screen are matched with those on the patient's face, calculating the precision of
      the needle placement. Discussion. The experience with EM navigation acquired with
      the radiofrequency technique can be transferred to other interventional pain
      management techniques, for instance, for the placement of a neuromodulation
      electrode close to the Gasserian ganglion. Currently, research is ongoing to
      extend the software of the navigation station for spinal application, and to
      adapt neurostimulation hardware to the EM navigation technology. This technology
      will allow neuromodulation techniques to be performed without x-ray exposure for
      the patient and the physician, and this with the precision of CT/MR imaging
      guidance.

PMID- 22151369
TI  - Revision of a superficially migrated percutaneous occipital nerve stimulator
      electrode using a minimally invasive technique.
AB  - Objective. Percutaneous techniques for occipital nerve stimulation have been in
      the literature since 1999. Lead migration continues to be the most common
      complication to the technique. The authors would like to introduce a new
      technique for revision of a superficially migrated occipital nerve stimulator
      electrode. Materials and Methods. Technical report of initial case where revision
      was performed. Results. The patient had successful revision of his superficially
      migrated occipital nerve stimulator using a new percutaneous approach. He had no
      signs of infection and full return of prior function of the stimulator at two
      weeks and three-month follow-up visits. Conclusion. This case demonstrates a new
      safer technique for revision of a superficially migrated occipital nerve
      stimulator lead. The technique is a more direct and simple solution to a common
      problem in the percutaneous placement of occipital nerve stimulators.

PMID- 22151371
TI  - Dredging for the anchor.

PMID- 22151370
TI  - Transforaminal nerve root stimulation: a technical report.
AB  - Objectives. This technical report provides a detailed description of a method of
      transforaminal nerve root stimulation useful in the treatment of chronic pain
      conditions. Material and Methods. We describe a patient who presented with a
      medically refractory peripheral neuropathy and suffered from bilateral foot pain.
      We utilized transforaminal nerve root stimulation to provide robust stimulation
      paresthesias to the painful areas. Implementing progressively angled stylets, we
      were able to successfully navigate the stimulators into the intervertebral
      foramenae with a retrograde approach. Results. The patient experienced
      appropriate pain relief after the stimulation and did not have any complications
      related to the procedure. Conclusions. We describe a method of transforaminal
      nerve root stimulation that can be easily implemented by providers using the
      standard tools available to them. Transforaminal nerve root stimulation may be
      appropriate for patients in whom more traditional approaches such as spinal cord
      stimulation or peripheral nerve stimulation are suboptimal.

PMID- 22151372
TI  - Predator mediated selection and the impact of developmental stage on viability in
      wood frog tadpoles (Rana sylvatica).
AB  - BACKGROUND: Complex life histories require adaptation of a single organism for
      multiple ecological niches. Transitions between life stages, however, may expose
      individuals to an increased risk of mortality, as the process of metamorphosis
      typically includes developmental stages that function relatively poorly in both
      the pre- and post-metamorphic habitat. We studied predator-mediated selection on
      tadpoles of the wood frog, Rana sylvatica, to identify this hypothesized period
      of differential predation risk and estimate its ontogenetic onset. We reared
      tadpoles in replicated mesocosms in the presence of the larval odonate Anax
      junius, a known tadpole predator. RESULTS: The probability of tadpole survival
      increased with increasing age and size, but declined steeply at the point in
      development where hind limbs began to erupt from the body wall. Selection
      gradient analyses indicate that natural selection favored tadpoles with short,
      deep tail fins. Tadpoles resorb their tails as they progress toward
      metamorphosis, which may have led to the observed decrease in survivorship. Path
      models revealed that selection acted directly on tail morphology, rather than
      through its indirect influence on swimming performance. CONCLUSIONS: This is
      consistent with the hypothesis that tail morphology influences predation rates by
      reducing the probability a predator strikes the head or body.

PMID- 22151373
TI  - Documentation of postoperative pain in the neonatal brachial plexus palsy
      population.
AB  - AIMS AND OBJECTIVES: To assess postoperative pain management in neonatal brachial
      plexus palsy children who underwent a primary nerve repair, release only and/or a
      release and transfer procedure. BACKGROUND: Previous studies have noted pain
      management inadequacies in postoperative pain management in certain paediatric
      populations. However, this is the first study to focus on postoperative pain
      management in this particular population. METHODS: Seventy-five patients, who
      underwent a primary nerve repair, release only and/or a release and transfer
      procedures at our institution, were reviewed. Postoperative pain management was
      assessed on a patient and drug administration level through appropriate pain
      scale use; appropriate dosage for the medication prescribed; appropriate
      reassessment of pain following medication administration; and complications
      leading to a longer hospital stay. RESULTS: Based on our institution's guidelines
      following drug administration, 64 patients were not appropriately reassessed for
      pain. Based on the drug's duration following drug administration, 40 patients
      were not appropriately reassessed for pain. Twenty-eight per cent of all
      medication administrations were not properly reassessed for pain based on the
      drug's duration and 62% of the time based on our institution's guidelines. Fifty
      per cent of all medication administrations were not properly dosed and 51
      patients were not appropriately dosed at least once during their hospital stay.
      Pain scales were documented incorrectly 20% of the time and administered
      improperly to 13 patients. CONCLUSIONS: Opportunities for improvement in
      postoperative pain management in the paediatric population - particularly those
      with neonatal brachial plexus palsy - exist. RELEVANCE TO CLINICAL PRACTICE:
      Findings from this study demonstrate that healthcare professionals may have (1)
      insufficient knowledge regarding pain and/or (2) inadequate direction and
      guidance to appropriately assess and document pain in the paediatric population.
      Improvements for these individual healthcare professionals and clinical settings
      are needed to overcome postoperative pain management issues in the future.

PMID- 22151374
TI  - Transient peripheral edema following displaced corneal graft after descemet
      stripping automated endothelial keratoplasty (DSAEK): case presentation.
AB  - BACKGROUND: Descemet's Stripping with Automated Endothelial Keratoplasty (DSAEK)
      is constantly gaining popularity in the management of endothelial dysfunctions
      such as bullous keratopathy or Fuchs' dystrophy. CASE PRESENTATION: A 36 year-old
      man with Fuchs' dystrophy underwent combined phacoemulsification and DSAEK of the
      right eye. Immediately postoperatively, corneal graft displacement and peripheral
      corneal edema which remained stable during the first postoperative month were
      evident on slit lamp examination. Three months after the procedure the peripheral
      edema had completely resolved and the patients' subjective symptoms were
      improved. CONCLUSIONS: The purpose of this case presentation is to demonstrate
      that corneal graft displacement after DSAEK can lead to peripheral corneal edema
      that can resolve without further intervention such as graft repositioning or
      replacement.

PMID- 22151375
TI  - "Tip-toeing" to an assay for transplantation tolerance?

PMID- 22151377
TI  - Bilateral implantation in globus pallidus internus and in subthalamic nucleus in
      Parkinson's disease.
AB  - Introduction. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and
      of the pars interna of Globus Pallidus (GPi) is used to improve parkinsonian
      symptoms and attenuate levodopa-induced motor complications in Parkinson's
      disease (PD) (DBS for PD study group, 2001). It is still not clear what the best
      anatomic structures to stimulate are or what the physiologic effects of DBS are.
      Most of the studies regarding DBS for parkinsonian symptoms have been conducted
      in patients with STN implantation, and these studies reported significant
      improvement in motor function with a relatively low rate of complication. The
      large experience of ablative surgery associated with the DBS experience of some
      groups worldwide indicate that GPi is a possible and very promising target for
      the management of parkinsonian symptoms. Surgical procedures have become safer
      and it is now possible, in selected cases, to target both structures in the same
      patient by means of the stereotactic system, "3P Maranello" (CLS-SRL, Italy).
      Using this system we were able to evaluate the clinical effects of simultaneous
      stimulation of both STN and GPi as well as evaluate the effects of isolated
      stimulation of each target. As it is known that there is a high intersubject
      variability of DBS, it seems relevant to test all different combinations of DBS
      in the same patient. Methods. We assessed the effects of DBS in 13 cases of PD,
      immediately after (30 min) stimulation and during chronic stimulation (weeks or
      months). Patients fell into two groups. The first (n = 7) responded to both GPi
      and STN stimulation equally. The second group (n = 6) was preferentially
      stimulated with only one target (STN = 5, GPi = 1). Results. There was a good
      reduction in levodopa treatment following surgery. Most patients remained were
      chronically treated with bilateral stimulation of both targets. Conclusion. We
      conclude that DBS of STN and GPi was effective, with most patients treated
      chronically with both targets stimulated.

PMID- 22151376
TI  - An increased risk of motor vehicle accidents after prescription of methadone.
AB  - AIMS: To investigate whether exposure to methadone affects the risk of motor
      vehicle accident with personal injury. DESIGN: Cohort study linking three
      Norwegian administrative registries using unique person identifiers. SETTING:
      Information was retrieved from the Norwegian Prescription Database on any
      prescriptions ever received by the individuals for methadone and all
      prescriptions for benzodiazepines. The Norwegian Road Accident Registry provided
      information about motor vehicle accidents involving personal injuries on
      Norwegian roads. The Central Population Registry provided demographic information
      on all residents in Norway. PARTICIPANTS: All Norwegian adults aged 18-69 years
      were observed for 2.5 years. MEASUREMENTS: Standardized incidence ratio (SIR) was
      calculated by comparing the incidence of traffic accidents with personal injuries
      in patients exposed to methadone with the incidence in those not exposed.
      FINDINGS: During the 4626 person-years observed in patients exposed to methadone,
      there were 26 motor vehicle accidents. There were very few accidents among the
      females who received methadone and they had no increased risk of being involved
      in motor vehicle accidents (SIR 1.1; 95% CI 0.2-3.1). We observed an increased
      risk of involvement in accidents among males (SIR 2.4; 95% CI 1.5-3.6). This
      figure did not change significantly when exposure to benzodiazepines was
      excluded. CONCLUSIONS: Men exposed to methadone appear to have an increased risk
      of being involved in motor vehicle accidents involving personal injuries. This
      increased risk could not be explained by exposure of benzodiazepines.

PMID- 22151378
TI  - Trigeminal branch stimulation for intractable neuropathic pain: technical note.
AB  - Intractable neuropathic facial pain resulting from injury to the peripheral
      branches of the trigeminal nerve presents a significant challenge for
      neurologists, pain specialists, and neurosurgeons. In this paper, we describe our
      technique of peripheral nerve stimulation of the infraorbital and supraorbital
      nerves to treat patients with medically intractable facial pain. Stimulation of
      the infraorbital and supraorbital nerves is performed using percutaneously
      inserted electrodes that are positioned in the epifascial plane, traversing the
      course of the infraorbital or supraorbital nerves. The temporary electrodes are
      inserted under fluoroscopic guidance and are anchored to the skin. A trial
      lasting a few days is followed, if successful, by insertion of a permanent
      electrode that is tunneled under the skin behind the ear toward the
      infraclavicular pocket, which houses the implantable pulse generator. Our
      technique of electrode insertion to stimulate the infraorbital or supraorbital
      nerves has been successfully used in several patients with neuropathic trigeminal
      pain of various etiologies. In patients who underwent permanent electrode
      implantation, stimulation resulted in long lasting pain relief; complications
      were rare and minor. We conclude that trigeminal branch stimulation is a simple
      technique that can be used in selected patients with neuropathic pain in the
      distribution of the infraorbital or supraorbital nerves. This procedure may
      provide relief of medically intractable pain, without the need for destructive
      procedures or more central modulation approaches.

PMID- 22151379
TI  - Application of spinal cord stimulation for the treatment of abdominal visceral
      pain syndromes: case reports.
AB  - Spinal cord stimulation (SCS) has traditionally been applied to the treatment of
      neuropathic pain with good to excellent outcomes. Visceral pain syndromes can be
      just as debilitating and disabling as somatic and neuropathic pain, however,
      there seems to be a general lack of consensus on appropriate treatment strategies
      for these disorders. We present here several case studies to demonstrate the
      viscerotomal distribution of abdominal visceral pain pathways and the application
      of traditional SCS techniques for its management. Nine patients, experiencing
      abdominal visceral pain due to various conditions including chronic nonalcoholic
      pancreatitis, post-traumatic splenectomy, and generalized abdominal pain
      secondary to laparotomies, were treated with SCS. Efficacy of treatment was
      evaluated using the Visual Analog Scale (VAS) for pain intensity and a reduction,
      if any, in opioid intake. There was an overall mean reduction of 4.9 points in
      the VAS score for pain intensity and a substantial (> 50%) decrease in narcotic
      use. All patients were followed for more than one year with excellent outcomes
      and minimal complications. We conclude, based on these case reports, that SCS
      might be an effective, nondestructive, and reversible treatment modality for
      abdominal visceral pain disorders.

PMID- 22151380
TI  - The development of a quality system for neuromodulation in the Netherlands.
AB  - We present here a descriptive article on the development of a national quality
      system for neuromodulatory techniques in the Netherlands. In 1994, due to
      reimbursement difficulties in the Netherlands, a Neuromodulation Working Group
      (WGN) undertook an initiative to develop a national quality system for
      neuromodulation. It was believed that with official recognition of
      neuromodulation as a therapy by the health authorities in the Netherlands, a
      quality system for monitoring would then follow. To that purpose an observational
      study was performed. Integration of this entire primary process (from intake to
      control phase) was based upon an inventory of the practices of the most
      experienced medical specialists practicing neuromodulation in the Netherlands.
      Based on the study data, nine quality indicators were identified that would allow
      monitoring of the quality of care to patients in the Netherlands. The study
      resulted in a positive feedback to the National Health Insurance Board and the
      Ministry of Health in the Netherlands. Neuromodulation for chronic pain and
      disabling spasticity is now recognized and fully reimbursed within the limits of
      the newly developed quality system. We therefore conclude that developed quality
      systems can provide a basis for medical specialists to cooperate around groups of
      patients or diseases. These quality systems can facilitate implementation and
      innovation within the health care system. The role of medical specialists and
      their will to cooperate is essential.

PMID- 22151381
TI  - The infection risk of intrathecal drug infusion pumps after multiple refill
      procedures.
AB  - The objective of this study was to evaluate the long-term infection risk from
      refilling intrathecal drug delivery devices. We studied 25 patients (14 females
      and 11 males) with intrathecal infusion pumps placed for spasticity (23 patients)
      and chronic pain (two patients). In this study group there were 890 refill
      procedures (mean 35.6 +/- 20.5; range 8-72 times) performed on an outpatient
      basis by four different physicians. All refill procedures were performed in a
      sterile and standardized fashion as suggested by the manufacturer, using
      manufacturer's approved kits for the refills. During the study period, five
      patients had recurrent infection of the urinary tract and three patients had
      recurrent infections of the respiratory tract. At the last pump refill of each
      patient, residual drug, extracted from the pump reservoir, was sent to a
      laboratory for aerobic and anaerobic cultures. All cultures, in all pumps, were
      negative for aerobic and anaerobic bacteria. We conclude that periodic refills of
      intrathecal implanted pumps do not seem to be a risk factor for infection if
      standard sterile refill procedures are performed. In this study, it was clear
      that comorbid infections from other parts of the body do not present as a risk
      for device contamination.

PMID- 22151382
TI  - Improved physical activity in patients treated for chronic pain by spinal cord
      stimulation.
AB  - The objective of this study was to objectively assess the physical activity of
      daily living in chronic pain patients treated with spinal cord stimulation (SCS).
      Changes in pain and spontaneous physical activity following SCS were evaluated
      under real life conditions. Five series of measurements were performed before the
      implant (baseline) and at one, three, six, and 12 months after the implantation
      of an SCS system. Compared to baseline values, physical activity increased
      consistently during the entire follow-up period. The time spent walking and
      standing was statistically increased after six months (p < 0.01) and the time
      spent lying decreased significantly (p < 0.001) at the same time. The average
      total walking distance increased up to 389% at 12 months, reaching statistical
      significance (p < 0.05) after three months. The stride length and the speed
      increased (p < 0.01) at all times. We conclude that the reduction in pain
      intensity due to SCS is associated with a progressive and sustained improvement
      in physical activity. j.

PMID- 22151383
TI  - Stretch reflex regulation in healthy subjects and patients with spasticity.
AB  - In recent years, part of the muscle resistance in spastic patients has been
      explained by changes in the elastic properties of muscles. However, the adaptive
      spinal mechanisms responsible for the exaggeration of stretch reflex activity
      also contribute to muscle stiffness. The available data suggest that no single
      spinal mechanism is responsible for the development of spasticity but that
      failure of different spinal inhibitory mechanisms (reciprocal IA inhibition,
      presynaptic inhibition, IB inhibition, recurrent inhibition) are involved in
      different patients depending on the site of lesion and the etiology of the
      spastic symptoms. A recent finding also shows no sign of exaggerated stretch
      reflexes in muscles voluntarily activated by the spastic patient in general. This
      is easily explained by the control of stretch reflex activity in healthy
      subjects. In healthy subjects, the stretch reflex activity is increased during
      voluntary muscle contraction in part because of depression of the inhibitory
      mechanisms that are affected in spasticity. In spastic patients, these inhibitory
      mechanisms are already depressed at rest and cannot be depressed further in
      connection with a contraction. In relation to most normal movements, antagonist
      muscles should remain silent and maximally relaxed. This is ensured by increasing
      transmission in several spinal inhibitory pathways. In spastic patients, this
      control is inadequate, and therefore stretch reflexes in antagonist muscles are
      easily evoked at the beginning of voluntary movements or in the transition from
      flexor to extensor muscle activity. This problem is contradicted by the fact that
      antispastic therapy to improve voluntary movements should be directed.

PMID- 22151384
TI  - Neuroprosthesis for retraining reaching and grasping functions in severe
      hemiplegic patients.
AB  - During the course of rehabilitation hemiplegic patients who have Chedoke McMaster
      Stages of Motor Recovery scores 4 and 5 measured three weeks after onset of
      stroke often improve their arm and hand function to the point that they can later
      use it in the activities of daily living (ADL) (1). These patients can be
      considered to have mild arm and hand paralysis since they can grasp objects and
      manipulate them with minor restrictions in the range of movement and force. On
      the other hand, hemiplegic patients who have Chedoke McMaster Stages of Motor
      Recovery scores 1 and 2 measured three weeks after onset of stroke, during the
      course of rehabilitation seldom improve their arm and hand function, and when
      they do, the improvements are not sufficient to allow these patients to use the
      arm and hand in ADL (1). These patients can be also described as patients who
      have severe arm and hand paralysis. Patients with severe arm and hand paralysis
      cannot move their arm and hand voluntarily at all or have very limited voluntary
      movements that cannot be used to carry out ADL. In recent years a variety of
      treatments such as constraint induced therapy, functional electrical therapy,
      biofeedback therapy, and robotics assisted therapies, were proposed which main
      objective is to improve reaching and grasping functions in subjects with
      unilateral arm paralysis. These therapies have shown encouraging results in
      patients with mild arm and hand paralysis. However, the efficacy of these
      therapies was limited when they were applied to patients with severe arm and hand
      paralysis. This article describes a new rehabilitation technique that can improve
      both reaching and grasping functions in hemiplegic patients with severe
      unilateral arm paralysis. A neuroprosthesis that applies surface electrical
      stimulation technology was used to retrain hemiplegic patients who had severe arm
      and hand paralysis to reach and grasp. The neuroprosthesis was applied both to
      acute and long-term hemiplegic patients. Patients who were treated with the
      neuroprosthesis were compared to those patients who were administered only
      standard physiotherapy and occupational therapy appropriate for hemiplegic
      patients with unilateral upper extremity paralysis (controls). The treated and
      control patients had approximately the same time allocated for arm and hand
      therapy. After the treatment program was completed, the patients treated with the
      neuroprosthesis significantly improved their reaching and grasping functions and
      were able to use them in ADL. However, the majority of the control patients did
      not improve their arm and hand functions significantly and were not able to use
      them in ADL.

PMID- 22151386
TI  - Skin cancer in organ transplant recipients: effects of immunosuppressive
      medications on DNA repair.
AB  - UV-induced skin cancers comprise a major problem in organ transplant recipients
      (OTRs). Cyclosporin A, a calcineurin inhibitor, is used as a standard
      immunosuppressant and clearly increases the skin cancer risk. Azathioprine does
      not appear to result in such an increase in skin cancer risk, and mTOR inhibitors
      are associated with an even lesser skin cancer risk. The underlying molecular
      mechanisms of these clinically important differences among immunosuppressants are
      still unclear and may relate to other than immunological effects. Insights may be
      gained by the multistep skin cancer theory and xeroderma pigmentosum, where
      defective nucleotide excision repair (NER) results in a cellular mutator
      phenotype and cutaneous carcinogenesis. This viewpoint assay summarizes current
      knowledge about the influence of the most commonly used immunosuppressive drugs
      in OTRs on DNA repair. Calcineurin inhibition results in a 200-fold increased
      skin cancer risk compared with the normal population and inhibits NER. The skin
      cancer risk under azathioprine is threefold less compared with calcineurin
      inhibitors, which may relate to inhibition of only the last step of NER, i.e. gap
      filling. mTOR inhibitors do not reduce NER in the global genome and can inhibit
      the growth of already initiated tumors, which may account for the markedly
      reduced skin cancer risk compared with calcineurin inhibitors. We conclude that
      OTRs may benefit from treatment regimens other than calcineurin inhibitors and
      speculate that a targeted modulation of calcineurin-dependent signalling may
      prevent UV-induced tumor formation by enhancing NER not only in OTRs but also in
      the general population, at least in part.

PMID- 22151387
TI  - Extended DNFB-induced contact hypersensitivity models display characteristics of
      chronic inflammatory dermatoses.
AB  - Despite recent developments, there is a high medical need for new treatment
      options for chronic inflammatory dermatoses like allergic contact dermatitis
      (ACD) and psoriasis. Particularly, more predictive skin inflammation models are
      required to facilitate the process of drug discovery. Murine contact
      hypersensitivity (CHS) models adequately reflect ACD and are also used to
      characterize therapeutic approaches for psoriasis. Using the hapten 2,4
      dinitrofluorobenzene (DNFB), we established new subacute and subchronic DNFB
      induced CHS models in C57BL/6 mice, which more closely reflect the
      characteristics of chronic T-cell-dependent inflammatory dermatoses as pronounced
      keratinocyte proliferation, strong hypervascularization, immune cell infiltration
      and overexpression of T cell and inflammatory cytokines. For the subacute DNFB
      model, we demonstrated anti-inflammatory activity of the glucocorticoid,
      prednisolone, as well as of neutralization of TNFalpha, IL-12/IL-23 or IL-18. In
      the subchronic DNFB-induced CHS model, deficiency for MyD88 and IL-12/IL-35 p35
      chain but not IL-12/IL-23 p40 chain led to decreased skin inflammation.
      Furthermore, as exemplified by the dose-dependently effective therapeutic
      prednisolone treatment, the subchronic model allows the continuous therapy of a
      pre-established stable contact dermatitis. Altogether, prolonged DNFB-induced
      mouse CHS models closely reflect ACD sensitive to glucocorticoids as standard
      therapy, reveal a more chronic skin inflammation and are responsive to cytokine
      antagonization.

PMID- 22151385
TI  - Phenotypic variation and host interactions of Xenorhabdus bovienii SS-2004, the
      entomopathogenic symbiont of Steinernema jollieti nematodes.
AB  - Xenorhabdus bovienii (SS-2004) bacteria reside in the intestine of the infective
      juvenile (IJ) stage of the entomopathogenic nematode, Steinernema jollieti. The
      recent sequencing of the X. bovienii genome facilitates its use as a model to
      understand host - symbiont interactions. To provide a biological foundation for
      such studies, we characterized X. bovienii in vitro and host interaction
      phenotypes. Within the nematode host X. bovienii was contained within a membrane
      bound envelope that also enclosed the nematode-derived intravesicular structure.
      Steinernema jollieti nematodes cultivated on mixed lawns of X. bovienii
      expressing green or DsRed fluorescent proteins were predominantly colonized by
      one or the other strain, suggesting the colonizing population is founded by a few
      cells. Xenorhabdus bovienii exhibits phenotypic variation between orange
      pigmented primary form and cream-pigmented secondary form. Each form can colonize
      IJ nematodes when cultured in vitro on agar. However, IJs did not develop or
      emerge from Galleria mellonella insects infected with secondary form. Unlike
      primary-form infected insects that were soft and flexible, secondary-form
      infected insects retained a rigid exoskeleton structure. Xenorhabdus bovienii
      primary and secondary form isolates are virulent towards Manduca sexta and
      several other insects. However, primary form stocks present attenuated virulence,
      suggesting that X. bovienii, like Xenorhabdus nematophila may undergo virulence
      modulation.

PMID- 22151388
TI  - Strain-dependent effects of the histamine H4 receptor antagonist JNJ7777120 in a
      murine model of acute skin inflammation.
AB  - The effects of the histamine H(4) receptor antagonist JNJ7777120 were evaluated
      in a model of acute skin inflammation induced by local application of croton oil.
      The influence of strain on the effect of JNJ7777120 was investigated in four
      different mouse strains (CD-1, NMRI, BALB/c and C57BL/6J). In CD-1 mice,
      JNJ777720 (30-100 mg/kg subcutaneously, s.c.) exerted a dose-dependent inhibition
      of croton oil-induced ear inflammation and polymorphonuclear leucocyte
      infiltration, as confirmed by histological evaluation of ear tissues. JNJ7777120
      (30-100 mg/kg) did not reduce ear oedema in NMRI, BALB/c or C57BL/6J mice. The
      positive control, dexamethasone (2 mg/kg s.c.) induced significant anti
      inflammatory effects only in CD-1 and NMRI mice. In these strains, also the
      histamine H(1) -receptor blocker pyrilamine (30 mg/kg s.c.) significantly reduced
      ear oedema at 2 h after croton oil challenge, being as effective as JNJ7777120 in
      CD-1 mice. Taken together, these data demonstrate that the H(4) receptor
      antagonist JNJ7777120 may reduce acute croton oil-induced skin inflammation as
      effectively as H(1) receptor blockade. However, present experiments evidenced for
      the first time marked strain-related differences in the JNJ7777120
      pharmacological activity, which have to be carefully considered when using this
      ligand to characterize histamine H(4) receptor functions in murine models and
      translating preclinical data to clinical human settings.

PMID- 22151389
TI  - In vivo assessment of peripheral vascular function by tcpO2 and skin blood flow
      modelling.
AB  - There are multiple techniques and methods to assess peripheral vascular function
      in vivo but not without limitations. More discriminative, sensitive and also
      practical evaluation strategies are needed to fully characterize the peripheral
      vascular function. In the present work, a new quantitative descriptor, the
      'elimination half-life time' was developed from flow-related variables as a non
      invasive microcirculatory rate parameter to describe vascular dynamics. Fifty
      four healthy volunteers and six type 2 diabetic patients, both genders, were
      submitted to a dynamical procedure consisting in the inhalation of a 100%
      saturated atmosphere of oxygen for 10 min. The tcpO(2) and microcirculatory blood
      flow [Laser Doppler Flowmetry (LDF)] were measured in a randomly selected leg
      with a Periflux 5000 system before, during and after the procedure. A
      monocompartmental model was adjusted to tcpO(2) and LDF data. The tcpO(2)
      constant elimination rate, expressed as the Oxygen elimination half-life, was
      used as an indicator of the vulnerability of peripheral tissue and compared in
      healthy versus non-healthy individuals. Under normal conditions, the saturated
      ventilation increases the tissue's O(2) availability, as an expression of the
      natural capacity to adjust the tissue hemodynamics to new metabolical/perfusion
      conditions. Diabetic patients are expected to suffer vascular impairment and
      ischemia. Under O(2) overloading conditions, those hypoxic territories tend to
      uptake all the delivered oxygen, expressed as a significant increase in the O(2)
      elimination half-life. This approach allows to propose 'elimination half-life
      time' as the first quantitative descriptive parameter combining miogenic,
      hemodynamic and metabolic aspects of the microcirculatory physiology and to help
      to identify the individual's vascular vulnerability.

PMID- 22151390
TI  - Leptin, adiponectin, visfatin and retinol-binding protein-4 - mediators of
      comorbidities in patients with psoriasis?
AB  - White adipose tissue is known to be involved in numerous physiological processes
      such as insulin-mediated functions, lipid and glucose metabolism, vascular
      changes and coagulation. These processes are mainly mediated by adipokines that
      are secreted either from adipocytes or cells of the stromal-vascular fraction of
      adipose tissue. In obesity, a shift in the production of adipokines can mediate
      the development of associated diseases, such as metabolic syndrome, and vascular
      complications, such as artherosclerosis, myocardial infarction or stroke, which
      are known comorbidities of psoriasis too. As obesity is a frequently seen
      comorbidity in psoriasis patients, adipokines could be involved in the
      pathogenesis of psoriasis and/or its comorbidities either dependently or
      independently from obesity. Therefore, this study investigates the levels of four
      major adipokines in psoriasis patients compared with a control group of healthy
      volunteers without chronic inflammatory diseases in relation to body composition.
      Leptin, adiponectin (high molecular weight (HMW) and total adiponectin), visfatin
      and retinol-binding protein 4 (RBP4) have been analysed in 79 psoriasis patients
      and in 80 healthy volunteers. It was shown that HMW adiponectin (OR 1.3755; P =
      0.0094) and visfatin (OR 1.1267; P = 0.0472) are independently increased, and
      RBP4 (OR 0.9884; P < 0.0001) is independently decreased in psoriasis. In
      conclusion, increased levels of HMW adiponectin and decreased levels of RBP4
      could be a mechanism in a chronic inflammatory state that helps to protect
      against vascular and metabolic disorders, whereas the increase of the pro
      inflammatory adipokine visfatin could lead to atherosclerosis and vascular
      disorders found in psoriasis.

PMID- 22151391
TI  - Non-invasive evaluation of dermal elastosis by in vivo multiphoton tomography
      with autofluorescence lifetime measurements.
AB  - The non-invasive differentiation of dermal elastic fibres from solar elastosis in
      vivo is of great interest in dermatologic research, especially for efficacy
      testing of anti-ageing products. To date, no studies on multiphoton excited
      fluorescence lifetime characteristics of human elastic fibres and solar elastosis
      are reported. The goal of the present work was the identification of differential
      criteria for elastic fibres and solar elastosis by the analysis of fluorescence
      decay curves acquired by time-correlated single photon counting in vivo
      multiphoton tomography. For this purpose, fluorescence lifetime measurements
      (FLIM) were performed with 47 volunteers of different age groups at sun-protected
      and sun-exposed localizations. Bi-exponential curve fitting was applied to the
      FLIM data, and characteristic differences between age groups and localizations
      were found in both relevant fit parameters describing the decay slope. The FLIM
      analyses have shown that dermal autofluorescence has different lifetimes
      depending on age and in part on localization.

PMID- 22151392
TI  - Participation of complement 3a receptor (C3aR) in the sensitization phase of Th2
      mediated allergic contact dermatitis.
AB  - The complement system has emerged as a bridge between innate and adaptive immune
      responses. An involvement of C3aR has been described during skin inflammation.
      The aim of the study was to investigate the role of C3a in a mouse model of
      allergic skin inflammation, such as allergic contact dermatitis (ACD) which is a
      clinical manifestation of contact sensitivity (CS). The sensitization phase was
      studied using the local lymph node test: Mice were sensitized on three
      consecutive days by application of non-irritant concentrations of toluene-2,4
      diisocyanate (TDI; 0.5%) onto the ear skin. On day 5, auricular draining lymph
      nodes were obtained. The elicitation phase was investigated by sensitization with
      TDI on the depilated and tape-stripped abdominal skin and challenge with TDI on
      the ear skin and measuring of ear swelling in vivo and cytokine secretion in
      activated splenocytes in vitro respectively. Complement 3a receptor deficient
      (C3aRKO) mice showed increased cytokine responses (interleukin[IL]-5, IL-6, IL
      17, granulocyte macrophage-colony stimulating factor [GM-CSF]) in the
      sensitization phase of ACD to TDI. However, no differences in CS responses to TDI
      were observed in C3aR KO mice compared with WT controls in the elicitation phase
      of ACD as assessed by measuring of ear swelling in vivo and cytokines in skin and
      in activated splenocytes in vitro, namely IL-1alpha, IL-2, IL-4, IL-5, IL-6, IL
      10, IL-17, interferon-gamma (IFN-gamma), GM-CSF and tumor necrosis factor (TNF)
      alpha. These findings provide a new insight into the participation of C3a in the
      sensitization phase of CS immune responses.

PMID- 22151393
TI  - Innate immune sensing 2.0 - from linear activation pathways to fine tuned and
      regulated innate immune networks.
AB  - The innate immune system is based on pathogen recognition receptors that bind
      conserved microbial molecular structures, so called pathogen-associated molecular
      patterns (PAMPs). The characterization of the innate immune system was long based
      on a linear step-wise concept of recognition, activation pathways and effector
      defense mechanisms. Only more recently it was recognized that the innate immune
      system needs regulatory elements, sideways and crosstalks that allows it to fine
      tune and adapt its response. Thus, it is an emerging field within innate immunity
      research to try to understand how the immune outcome of innate immune sensing is
      regulated and why immune responses can be substantially different, even though
      the same PAMPs may have been 'sensed' at the surface organs such as the skin.
      Only the expansion of the innate immune system from 'pure' linear activation
      pathways to fine tuned and regulated innate immune networks allows us to
      integrate the generation of gradually accentuated and qualitatively different
      effector and tolerogenic immune responses. This article provides a review of the
      basic concepts and players of the innate immune system and will present some of
      the newer data defining the innate immune networks effectively regulating the
      immune homoeostasis and immune effector mechanisms with special focus on the skin
      as one of the organs involved in regulating the immune interface between the
      environment and the organism.

PMID- 22151394
TI  - Bioactive reagents used in mesotherapy for skin rejuvenation in vivo induce
      diverse physiological processes in human skin fibroblasts in vitro- a pilot
      study.
AB  - The promise of mesotherapy is maintenance and/or recovery of a youthful skin with
      a firm, bright and moisturized texture. Currently applied medications employ
      microinjections of hyaluronic acid, vitamins, minerals and amino acids into the
      superficial layer of the skin. However, the molecular and cellular processes
      underlying mesotherapy are still elusive. Here we analysed the effect of five
      distinct medication formulas on pivotal parameters involved in skin ageing, that
      is collagen expression, cell proliferation and morphological changes using normal
      human skin fibroblast cultures in vitro. Whereas in the presence of hyaluronic
      acid, NCTF135((r))  and NCTF135HA((r)) , cell proliferation was comparable to
      control cultures; however, with higher expression of collagen type-1, matrix
      metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, addition
      of Soluvit((r))  N and Meso-BK led to apoptosis and/or necrosis of human
      fibroblasts. The data indicate that bioactive reagents currently applied for skin
      rejuvenation elicit strikingly divergent physiological processes in human skin
      fibroblast in vitro.

PMID- 22151395
TI  - CXC chemokine receptor 4 is essential for Lipo-PGE1-enhanced migration of human
      dermal fibroblasts.
AB  - Lipo-PGE1 [EGLANDIN((r)) ; a lipid microsphere-incorporated prostaglandin E1
      (PGE1)] stimulates angiogenesis and promotes the healing of skin ulcers. Because
      the effects of Lipo-PGE1 on cutaneous wound healing are not completely
      understood, we investigated the ability of Lipo-PGE1 to affect in vivo wound
      healing and regulate the migration of human dermal fibroblasts (HDFs). In a
      murine wound model, Lipo-PGE1 reduced the wound size compared with control mice.
      Lipo-PGE1 significantly increased HDF migration in a dose- and time-dependent
      manner. Lipo-PGE1 markedly increased the expression of CXC chemokine receptor 4
      (CXCR4), which controls the migration of HDFs, at the mRNA and protein levels.
      Small interfering RNA (siRNA)-mediated knockdown of CXCR4 inhibited Lipo-PGE1
      enhanced HDF migration. Moreover, Lipo-PGE1 directly induced the phosphorylation
      of c-Jun N-terminal kinase (JNK), and the JNK-specific inhibitor Sp6000125
      blocked Lipo-PGE1-enhanced migration and CXCR4 expression of HDFs. Our results
      demonstrate that Lipo-PGE1 accelerates wound healing in vivo and increases the
      CXCR4-mediated migration of HDFs through the JNK pathway.

PMID- 22151396
TI  - Perivascular localization of dermal stem cells in human scalp.
AB  - In mammalian skin, the existence of stem cells in the dermis is still poorly
      understood. Previous studies have indicated that mesenchymal stem cells (MSCs)
      are situated as pericytes in various mammalian tissues. We speculated that the
      human adult dermis also contains MSC-like cells positive for CD34 at perivascular
      sites similar to adipose tissue. At first, stromal cells from adult scalp skin
      tissues showed colony-forming ability and differentiated into mesenchymal
      lineages (osteogenic, chondrogenic and adipogenic). Three-dimensional analysis of
      scalp skin with a confocal microscope clearly demonstrated that perivascular
      cells were positive for not only NG2, but also CD34, immunoreactivity.
      Perivascular CD34-positive cells were abundant around follicular portions.
      Furthermore, CD34-positive cell fractions collected with magnetic cell sorting
      were capable of differentiating into mesenchymal lineages. This study suggests
      that dermal perivascular sites act as a niche of MSCs in human scalp skin, which
      are easily accessible and useful in regenerative medicine.

PMID- 22151397
TI  - PEG matrix enables cell-mediated local BMP-2 gene delivery and increased bone
      formation in a porcine critical size defect model of craniofacial bone
      regeneration.
AB  - PURPOSE: This study addressed the suitability of a polyethylene glycol (PEG)
      matrix as scaffold for cell-mediated local BMP-2 gene transfer in a calvarial
      critical size defect (CSD) model. MATERIALS AND METHODS: PEG matrix (degradation
      time 10 days) and PEG membrane (degradation time 120 days) were used in the pig
      calvarial model. Cylindrical (1 * 1 cm) CSD (9 per animal; 20 animals) were
      filled with: (i) HA/TCP, covered by PEG membrane (group 1); (ii) HA/TCP, mixed
      with PEG matrix (group 2); and (iii) HA/TCP mixed with BMP-2 transfected
      osteoblasts and PEG matrix (group 3). BMP-2/4 gene transfer: liposomal in vitro
      transfection of BMP-2/V5-tag fusion-protein. Quantitative histomorphometry
      (toluidine blue staining) after 2, 4 and 12 weeks assessed bone formation.
      Semiquantitative immunohistochemistry estimated the expression of BMP-2 and V5
      tag. RESULTS: Group 3 showed significantly higher new bone formation than groups
      1, 2 at 4 (P < 0.05) and 12 (P < 0.02) weeks. BMP-2-V5-tag was detected for 4
      weeks. BMP-2 expression in group 3 was higher compared to all other groups after
      2 and 4 (P < 0.02) weeks. CONCLUSIONS: The PEG matrix serves as scaffold for cell
      mediated BMP-2 gene delivery in guided bone regeneration facilitating cell
      survival and protein synthesis for at least 4 weeks. Local BMP-2 gene delivery by
      PEG matrix-embedded cells leads to increased bone formation during critical size
      defect regeneration.

PMID- 22151398
TI  - Use of zero-valent iron biosand filters to reduce Escherichia coli O157:H12 in
      irrigation water applied to spinach plants in a field setting.
AB  - AIMS: Zero-valent iron (ZVI) filters may provide an efficient method to mitigate
      the contamination of produce crops through irrigation water. METHODS: A field
      scale system was utilized to evaluate the effectiveness of a biosand filter (S),
      a biosand filter with ZVI incorporated (ZVI) and a control (C, no treatment) in
      decontaminating irrigation water. An inoculum of c.8.5log CFU100ml(-1) of
      Escherichia coli O157:H12 was introduced to all three column treatments in 20-l
      doses. Filtered waters were subsequently overhead irrigated to 'Tyee' spinach
      plants. Water, spinach plant and soil samples were obtained on days 0, 1, 4, 6,
      8, 10, 13 and 15 and analysed for E. coli O157:H12 populations. RESULTS: ZVI
      filters inactivated c.6logCFU100ml(-1) E. coli O157:H12 during filtration on day
      0, significantly (P<0.05) more than S filter (0.49CFU100ml(-1)) when compared to
      control on day 0 (8.3log CFU100ml(-1)). On day 0, spinach plants irrigated with
      ZVI-filtered water had significantly lower E. coli O157 counts (0.13logCFUg(-1))
      than spinach irrigated with either S-filtered (4.37logCFUg(-1)) or control
      (5.23logCFUg(-1)) water. Soils irrigated with ZVI-filtered water contained E.
      coli O157:H12 populations below the detection limit (2logCFUg(-1)), while those
      irrigated with S-filtered water (3.56logCFUg(-1)) were significantly lower than
      those irrigated with control (4.64logCFUg(-1)). CONCLUSIONS: ZVI biosand filters
      were more effective in reducing E. coli O157:H12 populations in irrigation water
      than sand filters. SIGNIFICANCE AND IMPACT OF THE STUDY: Zero-valent ion
      treatment may be a cost-effective mitigation step to help small farmers reduce
      risk of foodborne E. coli infections associated with contamination of leafy
      greens.

PMID- 22151400
TI  - Does dual lead stimulation favor stimulation of the axial lower back?

PMID- 22151401
TI  - Treatment of chronic pain in failed back surgery patients with spinal cord
      stimulation: a review of current literature and proposal for future
      investigation.
AB  - Objective. The authors attempted to design and conduct a randomized, prospective
      study to investigate the efficacy of spinal cord stimulation (SCS) for patients
      with chronic back and leg pain following at least one previous surgery. While the
      scientific advantages of the randomized, prospective trial are considerable, the
      authors encountered numerous practical and ethical difficulties with conducting
      these trials. These are reviewed and an alternative investigative technique
      proposed. Materials and Methods. The literature on interventional and minimally
      invasive treatments for this population group is reviewed, and the strengths and
      weaknesses of different methodologies for conducting clinical research in an
      interventional setting are examined. Results. The difficulties inherent in a
      randomized, prospective study for an intervention vs. a nonintervention group are
      addressed, and an alternative methodology is proposed-that of a randomized
      interventional design. In this design, patients are assigned to a given treatment
      group, with each treatment exclusively available at different centers.
      Conclusions. By utilizing a randomized interventional study design, problems of
      comparability of procedures, provider reluctance to participate in randomized
      clinical trials, provider bias, detection bias, and transfer bias are eliminated.
      It is suggested that future investigations, particularly those which are
      interventionally or device-based, conform to this particular model.

PMID- 22151399
TI  - Gastrointestinal effects of the addition of ascorbic acid to aspirin.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been
      associated with the damage to the gastrointestinal tract. One proposed mechanism
      of injury to the gastrointestinal mucosa by NSAIDs is oxygen radical-dependent
      microvascular injury. There is reasonable evidence to support the benefit of the
      addition of ascorbic acid, an ingredient with antioxidant properties, to moderate
      the adverse gastrointestinal (GI) effects of aspirin. Pharmacokinetic data have
      demonstrated that aspirin and ascorbic acid combination therapy can assist in
      mitigating the decrease in levels of ascorbic acid secondary to aspirin
      monotherapy. Endoscopic evaluation has demonstrated that the addition of ascorbic
      acid to aspirin significantly improves Lanza scores and rates of blood loss when
      compared to aspirin administration alone. When taken with ascorbic acid, the
      patient-reported tolerability of aspirin has been shown to be comparable to
      paracetamol and placebo. The existing body of evidence is relevant to short-term
      therapy with analgesic aspirin doses, and extrapolation to long-term therapy with
      low-dose aspirin is not appropriate. The purported benefit of an aspirin and
      ascorbic acid combination is a local observance and is not suspected to influence
      the adverse GI effects experienced as a result of systemic prostaglandin
      inhibition. Nevertheless, ascorbic acid may be a viable addition to the
      strategies employed to improve the gastrointestinal tolerability of aspirin.

PMID- 22151402
TI  - Intrathecal baclofen for the treatment of intractable spasticity of spine or
      brain etiology.
AB  - Objective. To determine the long-term relief of spasticity and complication rates
      in patients who underwent placement of a programmable intrathecal baclofen pump
      for treatment of medically intractable spasticity of spine or brain etiology.
      Methods. Sixty-two consecutive adult patients who underwent placement of a
      programmable pump were retrospectively reviewed. Results. Spasticity was
      clinically and statistically significantly decreased in all patients. Catheter
      related kinks, breaks, dislodgments, and disconnections were the most common
      complications followed by drug-related effects, infections, and wound
      complications. Conclusions. Intrathecal baclofen is a very effective strategy for
      the relief of medically intractable spasticity of spine or brain etiology. Even
      though 36% of patients have required revisions, no patient has experienced any
      long-term morbidity. Patients and their primary care givers have been pleased
      with the long-term effects of this therapy upon quality of life.

PMID- 22151403
TI  - Intradiscal Electrothermal Annuloplasty (IDET): A Novel Approach for Treating
      Chronic Discogenic Back Pain.
AB  - Objective. This one-year pilot outcome study was designed to investigate
      prospectively a series of patients with chronic discogenic back pain who
      underwent intradiscal electrothermal annuloplasty (IDET). Patients with chronic
      discogenic low back pain usually respond poorly to conservative medical care.
      Spinal fusion procedures have yielded mixed results. IDET is a new procedure to
      heat the intervertebral disc for the purpose of relieving discogenic pain. This
      study presents the one-year results for the first 32 patients undergoing the IDET
      procedure. The objective of this article is to determine the safety and efficacy
      of the IDET procedure in patients with chronic discogenic back pain. Methods.
      Utilizing standard discographic technique, the disc was heated using a navigable
      intradiscal catheter with a temperature-controlled thermal resistive coil. Six
      month and one-year outcomes were assessed comparatively within subjects using a
      Roland-Morris (RM) questionnaire and a Visual Analog Scale (VAS), and between
      subjects using the NASS Low Back Pain Outcome Assessment Instrument Satisfaction
      Index and a general activity scale modified from the back pain/disability scale
      from the same instrument. The results from the individual outcome measures were
      combined to generate an overall outcome of favorable, nonfavorable, and no
      change. Results. There were no significant differences between overall outcome
      measures at 6-month and 12-month follow-ups. At 12 month follow-up the VAS had a
      mean decrease of 1.84 (sd = 2.38) and the RM had a mean decrease of 4.03 (sd =
      4.82). 78.1% of patients stated that the procedure met their expectations or that
      they would undergo the same treatment for the same outcome. 53.1% of patients
      stated that their overall activity level was either better or much better
      compared to before the procedure. Overall, 62.5% had a favorable outcome, 12.5%
      nonfavorable, and 25% no change. Patients with excellent or good catheter
      positions and those with low pressure sensitive discs on preoperative discography
      had the most favorable outcomes. There were no significant complications.
      Conclusions. One-year pilot study outcome results suggest that IDET may be an
      effective, minimally invasive treatment for chronic discogenic low back pain.

PMID- 22151404
TI  - Spinal cord stimulation in the treatment of chronic critical limb ischemia:
      review of clinical experience.

PMID- 22151405
TI  - Electrical activation of spinal neural circuits: application to motor-system
      neural prostheses.
AB  - Present motor-system neural prostheses use electrical activation of last-order
      (motor) neurons to restore function. We are pursuing a new approach: restoration
      of function by electrical activation of higher-order interneurons. Our hypothesis
      is that electrical activation of spinal neural circuits, rather than direct
      activation of last-order motoneurons, will simplify generation of complex motor
      behaviors. We review two approaches to control bladder function and to control
      skeletal motor function: intraspinal microstimulation for direct activation of
      spinal neurons and peripheral afferent stimulation for indirect, synaptic
      activation of spinal neurons. The results demonstrate that electrical activation
      of spinal neural circuits allows generation of complex motor behaviors including
      micturition and organized multi-joint motor responses with a single electrode.
      Electrical activation of spinal neural circuits, and generation of the complex
      functions they subserve, holds great promise to advance the function of motor
      system neural prostheses.

PMID- 22151406
TI  - Soleus stretch reflex inhibition in the early swing phase of gait using deep
      peroneal nerve stimulation in spastic stroke participants.
AB  - Objectives. To investigate the feasibility of inhibiting the stretch reflex of
      the soleus muscle by a conditioning stimulus applied to the deep peroneal nerve
      in spastic stroke participants during the early swing phase of gait. Materials
      and Methods. This study investigated the effect of an electrical conditioning
      stimulus applied to the deep peroneal nerve on the magnitude at the peak of the
      soleus stretch reflex in the early swing phase of gait in six spastic stroke
      participants. Results. Five of the six participants showed a reduced stretch
      reflex of more than 80%. On average (n= 4), it was shown that maximal inhibition
      occurred at a conditioning-test interval of 114 ms and had a magnitude of more
      than 90% (p < 0.05). For all five participants investigated, there was a
      significant reduction in the sensitivity of the soleus stretch reflex after
      conditioning (p < 0.02). Conclusions. It is concluded that the inhibition of the
      soleus stretch reflex with an electrical conditioning stimulus applied to the
      deep peroneal nerve is feasible in the early swing phase of walking. This shows a
      potential for being used in the rehabilitation of walking by spastic stroke
      persons.

PMID- 22151407
TI  - Implantable defibrillator electrograms and origin of left ventricular impulses:
      an analysis of regionalization ability and visual spatial resolution.
AB  - INTRODUCTION: The implantable cardioverter-defibrillator (ICD) electrogram (EG)
      is a documentation of ventricular tachycardia. We prospectively analyzed EGs from
      ICD electrodes located at the right ventricle apex to establish (1) ability to
      regionalize origin of left ventricle (LV) impulses, and (2) spatial resolution to
      distinguish between paced sites. METHODS AND RESULTS: LV electro-anatomic maps
      were generated in 15 patients. ICD-EGs were recorded during pacing from 22 +/- 10
      LV sites. Voltage of far-field EG deflections (initial, peak, final) and time
      intervals between far-field and bipolar EGs were measured. Blinded visual
      analysis was used for spatial resolution. Initial deflections were more negative
      and initial/peak ratios were larger for lateral versus septal and superior versus
      inferior sites. Time intervals were shorter for apical versus basal and septal
      versus lateral sites. Best predictive cutoff values were voltage of initial
      deflection <-1.24 mV, and initial/peak ratio >0.45 for a lateral site, voltage of
      final deflection <-0.30 for an inferior site, and time interval <80 milliseconds
      for an apical site. In a subsequent group of 9 patients, these values predicted
      correctly paced site location in 54-75% and tachycardia exit site in 60-100%.
      Recognition of paced sites as different by EG inspection was 91% accurate.
      Sensitivity increased with distance (0.96 if >= 2 cm vs 0.84 if < 2 cm, P <
      0.001) and with presence of low-voltage tissue between sites (0.94 vs 0.88, P <
      0.001). CONCLUSIONS: Standard ICD-EG analysis can help regionalize LV sites of
      impulse formation. It can accurately distinguish between 2 sites of impulse
      formation if they are >=2 cm apart.

PMID- 22151408
TI  - Translation, validation, and construct reliability of a Portuguese version of the
      Xerostomia Inventory.
AB  - OBJECTIVES: To generate and validate at pretest level a cross-culturally adapted
      Portuguese version of Xerostomia Inventory (XI), a 11-item questionnaire designed
      to measure specific xerostomia rating of patients complaints. METHODS: The
      original English version of the XI was translated into Portuguese following the
      guidelines for cross-cultural adaptation of health-related quality of life
      measures. Thirty patients with primary Sjogren syndrome were recruited for this
      study. The questionnaires were administered by trained and calibrated dental
      doctors to each patient. XI properties were examined including reliability,
      internal consistency, and test-retest reliability, using Cronbach's alpha, total
      and inter-item correlation, and intra-class correlation coefficients (ICC),
      respectively. Construct validity supported by objective measurements of
      xerostomia intra-oral signs and salivary secretion was investigated. Alpha was
      set at 0.05. Informed consents and local ethical committee clearance were
      obtained. RESULTS: Internal consistency and test-retest reliability were
      excellent (Cronbach's alpha=0.9; ICC range=0.79-0.94). Scatterplot interpolation
      and Pearson correlation coefficient suggested the presence of a strong, negative,
      and significant correlation between salivation and the XI scores indicating
      construct validity. CONCLUSION: The Portuguese version of the XI can be
      considered a reliable and valid instrument to measure patients' xerostomia
      symptoms.

PMID- 22151410
TI  - Nurse-led education and counselling to enhance adherence to phosphate binders.
AB  - AIMS AND OBJECTIVES: To investigate whether nurse-led education and counselling
      enhance phosphate binder adherence in chronic dialysis patients. BACKGROUND: One
      in two chronic dialysis patients experiences difficulties in adhering to
      phosphate binders. The reasons for non-adherence are multifactorial and
      accordingly require a multifaceted strategy. To date, investigations have been
      confined primarily to single interventions to promote adherence. This study
      examines the effect of a multifaceted approach. DESIGN: The design was
      interventional. METHOD: Adherence to phosphate binders was blindly and
      electronically monitored for 17 consecutive weeks with the Medication Event
      Monitoring System (MEMS). After four weeks baseline monitoring, the effects of
      the intervention were studied for an additional 13 weeks. In week 5, the study
      nurse gave all 41 participating patients education on phosphate binders.
      Thereafter, the study nurse gave bi-weekly personalised counselling to enhance
      adherence to phosphate binders. The evolution of adherence over time was assessed
      and compared with historical control data. Secondary outcome variables included
      serum values of phosphate, calcium and parathyroid hormone and phosphate binder
      knowledge. RESULTS: In week 1, mean adherence was 83% in this study (intervention
      group), compared with 86% in the historical control group. In the intervention
      group, mean adherence increased from 83-94% after 13 weeks. By contrast, in the
      historical control group, mean adherence declined from 86-76%. In the
      intervention group, serum phosphate values decreased from 4.9-4.3 mg/dl and
      phosphate binder knowledge increased from a mean score of 53-75%. CONCLUSIONS:
      Combining education and continuous counselling holds promise in enhancing
      phosphate binder adherence. Large-scaled and long-term field studies are
      indicated to determine which nurse-led practices lead to an integral and
      sustained medication adherence management. RELEVANCE TO CLINICAL PRACTICE:
      Nursing strategies to scale up adherence should at least include educating
      patients and regularly reinforcing adherence behaviour.

PMID- 22151409
TI  - Flow-mediated vasodilation measurements in Cavalier King Charles Spaniels with
      increasing severity of myxomatous mitral valve disease.
AB  - BACKGROUND: Cardiovascular disease is associated with endothelial dysfunction in
      humans and studies of plasma biomarkers suggest that dogs with myxomatous mitral
      valve disease (MMVD) might also have endothelial dysfunction. HYPOTHESIS: That
      progression of mitral regurgitation (MR) is associated with development of
      endothelial dysfunction. ANIMALS: Forty-three Cavalier King Charles Spaniels
      (CKCS) with MR of varying severity. METHODS: Privately owned CKCS were
      prospectively recruited and divided in 4 groups: (1) 12 CKCS with minimal MR; (2)
      9 CKCS with mild MR; (3) 11 CKCS with moderate-severe MR; and (4) 11 CKCS with
      moderate-severe MR and clinical signs compatible with heart failure. Dogs
      underwent blood sampling, echocardiography, blood pressure (BP) recordings, and
      flow-mediated vasodilation (FMD) measurements. The effect of progressive MR on
      FMD was determined by multivariate analyses. RESULTS: Flow-mediated vasodilation
      decreased with progression of MR. Group 4 (4.79 +/- 3.22%) had significantly
      lower FMD than groups 1 (10.40 +/- 4.58%) and 2 (10.14 +/- 3.67%) (P < .005) and
      group 3 (6.79 +/- 3.98%) had a significantly lower FMD than group 1 (P = .03).
      Increasing left ventricular end-diastolic diameter (P = .0004, R(2) = 0.27) and
      the combination of age (P = .01) and body weight (P = .002) (R(2) = 0.31) were
      significantly associated with reduced FMD. FMD did not correlate with sex, BP, or
      plasma markers. CONCLUSIONS AND CLINICAL IMPORTANCE: Reduced FMD indicates that
      increased disease severity in CKCS with MMVD is associated with development of
      endothelial dysfunction which might be a future therapeutic and/or diagnostic
      target.

PMID- 22151411
TI  - An analysis of potential risk factors for early complications from fiberoptic
      bronchoscopy in lung transplant recipients.
AB  - Several reviews exist describing the safety of bronchoscopy in lung transplant
      recipients. However, the incidence of bronchoscopic complications in lung
      transplant recipients in relation to trainee involvement, and clinical
      characteristics such as pre-transplant diagnosis and transplant type, has not
      been described. We performed a retrospective cohort study of all lung transplant
      recipients undergoing flexible fiberoptic bronchoscopy (n = 259) at the
      University of California, San Francisco, between January, 2003, and June, 2009.
      Complications included bleeding, pneumothorax, aspiration, oversedation, and
      hypoxemia. From 2003 to 2009, 3734 flexible fiberoptic bronchoscopies were
      performed, including 2111 (57%) with transbronchial biopsies. Trainees were
      involved in 2102 bronchoscopies (56%), including 1046 transbronchial biopsies
      (49.5%). Complications occurred in 27 bronchoscopies [0.7% (95% Confidence
      Interval [CI]: 0.4-1.0)], with 10 involving a trainee (37%). Twenty (74%)
      occurred during bronchoscopies with transbronchial biopsies. Six of these
      involved a trainee, while 14 involved an attending alone (P = 0.03). We did not
      find differences in pre-transplant diagnosis, transplant type, lung, or renal
      function between subjects who suffered a complication and those who did not (P >=
      0.30). The involvement of trainees, pre-transplant diagnosis, and transplant type
      do not significantly impact the rate of bronchoscopic complications in lung
      transplant recipients.

PMID- 22151412
TI  - A capillary blood ammonia bedside test following glutamine load to improve the
      diagnosis of hepatic encephalopathy in cirrhosis.
AB  - BACKGROUND: Hepatic encephalopathy (HE) is a frequent and severe complication of
      cirrhosis. A single determination of ammonia in venous blood correlates poorly
      with neurological symptoms. Thus, a better biological marker is needed. AIM: To
      make a diagnosis of HE, we explored the value of ammonia in capillary blood, an
      equivalent to arterial blood, measured at bedside following an oral glutamine
      challenge. METHODS: We included 57 patients (age 56 yrs; M/F: 37/20) with
      cirrhosis (alcoholic = 42; MELD score 13.8 [7-29], esophageal varices = 38) and
      previous episodes of HE (n = 19), but without neurological deficits at time of
      examination, and 13 healthy controls (age 54 yrs). After psychometric tests and
      capillary (ear lobe) blood ammonia measurements, 20 gr of glutamine was
      administered orally. Tests were repeated at 60 minutes (+ blood ammonia at 30').
      Minimal HE was diagnosed if values were > 1.5 SD in at least 2 psychometric
      tests. Follow-up lasted 12 months. RESULTS: The test was well tolerated (nausea =
      1; dizziness = 1). Patients showed higher values of capillary blood ammonia over
      time as compared to controls (0'-30'-60 minutes: 75, 117, 169 versus 52, 59, 78
      umol/L, p < 0.05). At baseline, 25 patients (44%) had minimal HE, while 38
      patients (67%) met the criteria for HE at 60 minutes (chi2: p < 0.01). For the
      diagnosis of minimal HE, using the ROC curve analysis, baseline capillary blood
      ammonia showed an AUC of 0.541 (CI: 0.38-0.7, p = 0.6), while at 60 minutes the
      AUC was 0.727 (CI: 0.58-0.87, p < 0.006). During follow-up, 18 patients (31%)
      developed clinical episodes of HE. At multivariate analysis, the MELD score (1.12
      [1.018-1.236]), previous episodes of HE (3.2[1.069-9.58]), but not capillary
      blood ammonia, were independent predictors of event. CONCLUSIONS: In patients
      with cirrhosis and normal neurological examination, bedside determination of
      ammonia in capillary blood following oral glutamine load is well tolerated and
      achieves a better diagnostic performance for minimal HE than basal capillary
      ammonia levels. However, capillary blood ammonia is a poor predictor of
      development of clinically overt HE.

PMID- 22151414
TI  - Guest editorial.

PMID- 22151413
TI  - Fatty acyl-CoA reductases of birds.
AB  - BACKGROUND: Birds clean and lubricate their feathers with waxes that are produced
      in the uropygial gland, a holocrine gland located on their back above the tail.
      The type and the composition of the secreted wax esters are dependent on the bird
      species, for instance the wax ester secretion of goose contains branched-chain
      fatty acids and unbranched fatty alcohols, whereas that of barn owl contains
      fatty acids and alcohols both of which are branched. Alcohol-forming fatty acyl
      CoA reductases (FAR) catalyze the reduction of activated acyl groups to fatty
      alcohols that can be esterified with acyl-CoA thioesters forming wax esters.
      RESULTS: cDNA sequences encoding fatty acyl-CoA reductases were cloned from the
      uropygial glands of barn owl (Tyto alba), domestic chicken (Gallus gallus
      domesticus) and domestic goose (Anser anser domesticus). Heterologous expression
      in Saccharomyces cerevisiae showed that they encode membrane associated enzymes
      which catalyze a NADPH dependent reduction of acyl-CoA thioesters to fatty
      alcohols. By feeding studies of transgenic yeast cultures and in vitro enzyme
      assays with membrane fractions of transgenic yeast cells two groups of isozymes
      with different properties were identified, termed FAR1 and FAR2. The FAR1 group
      mainly synthesized 1-hexadecanol and accepted substrates in the range between 14
      and 18 carbon atoms, whereas the FAR2 group preferred stearoyl-CoA and accepted
      substrates between 16 and 20 carbon atoms. Expression studies with tissues of
      domestic chicken indicated that FAR transcripts were not restricted to the
      uropygial gland. CONCLUSION: The data of our study suggest that the identified
      and characterized avian FAR isozymes, FAR1 and FAR2, can be involved in wax ester
      biosynthesis and in other pathways like ether lipid synthesis.

PMID- 22151415
TI  - Inhibition of histamine-induced bronchoconstriction in Guinea pig and Swine by
      pulsed electrical vagus nerve stimulation.
AB  - Objective. Smooth muscle help regulate the diameter of the airways and their
      constriction can contribute to the pathology of acute asthma attacks. This study
      sought to determine if applying a specific electrical signal to the vagus nerve
      (VN) could minimize histamine-induced bronchoconstriction. Methods. Sixteen
      guinea pigs and three swine were anesthetized and had bipolar electrodes
      positioned on the cervical VNs. After the animals stabilized, i.v. histamine was
      titrated to elicit a moderate 2-4 cm H(2) O increase in pulmonary inflation
      pressure (Ppi). Histamine was then dosed with or without concurrent low voltage
      VN stimulation. Results. The peak change in Ppi following a histamine challenge
      was reduced in the guinea pig by VN stimulation (3.4 +/- 0.4 vs. 2.1 +/- 0.2 cm
      H(2) O, p < 0.001). The results were confirmed in a limited study in swine and
      indicate VN treatment is applicable to larger animals. Conclusion. This study
      suggests that VN stimulation can reduce bronchoconstriction and may prove useful
      as a rescue therapy in the treatment of acute asthma.

PMID- 22151416
TI  - Deep brain stimulation for epilepsy.
AB  - Introduction. There is renewed interest in the use of electrical stimulation to
      control seizures in patients with medically refractory epilepsy. The evidence
      indicates that multiple nuclei are involved in the onset, spread, or termination
      of seizures. Establishing electrical stimulation parameters tailored to these
      nuclei that best control seizures is ongoing. Methods. The aim of this article is
      to review the published literature on electrical stimulation of the brain for
      epilepsy in animals and humans. Results. Animal and human research efforts have
      focused primarily on the study of the cerebellum, anterior thalamus, centromedian
      thalamus, substania nigra, caudate nucleus, subthalamic nucleus, and amygdalo
      hippocampal complex. Electrical stimulation of deep brain nuclei has in some
      instances controlled seizures and epilepsy. The advent of seizure detection
      devices used in closed-loop studies has in part redefined the strategy to prevent
      seizure occurrence and limit spread. Discussion. A number of studies in animals
      and humans indicate that electrical stimulation may be an alternative treatment
      for some patients with medically intractable epilepsy who are not candidates for
      conventional surgical options. Conclusion. The reduction in the number and/or
      severity of seizures found in some studies supports further investigation into
      the effects of electrical stimulation on the brain and the continuation of
      testing in animals and humans.

PMID- 22151417
TI  - Spinal cord stimulation in the first two trimesters of pregnancy: case report and
      review of the literature.
AB  - Introduction. Spinal cord stimulation (SCS) is an accepted cost-effective therapy
      for many chronic pain syndromes. Its effects on pregnancy have not been studied
      because of stringent regulation and manufacturers' recommendations. However,
      childbearing women who had SCS become or choose to become pregnant despite these
      policies. It is paramount to monitor, document, and report these effects of SCS
      during pregnancy to build clinical experience and guide recommendations and
      management. Methods. We reviewed the literature for SCS in pregnancy and added
      new case report of a young woman who had SCS implanted for chronic pain, became
      pregnant and at the end of the second trimester the lead extender had to be
      divided to relief pain at the lead site. Results. We found only one previous case
      report in this field and we add another case. Discussion. Our case is different
      from the previously reported case in that the implantable pulse generator (IPG)
      of our case was implanted in the anterior abdominal wall, while the previously
      reported case was implanted in the subclavicular fossa. Therefore our case
      highlights the need to implant the IPG in a way that avoids stretching the lead
      extender by the expanding abdomen. Conclusion. SCS seems to be safe in the first
      two trimesters of pregnancy based on these two case reports and the abdominal
      wall should be avoided as a site for IPG implantation in these patients. However,
      more cases are required to establish the safety of SCS in pregnancy.

PMID- 22151418
TI  - Lumbar sympathetic chain neuromodulation with implanted electrodes for long-term
      pain relief in loin pain haematuria syndrome.
AB  - Introduction. Loin pain-hematuria syndrome (LPHS) is a rare clinical entity
      causing unilateral or bilateral intractable flank and loin pain with hematuria.
      The etiology is poorly understood, and the diagnosis is made by exclusion of
      urological and nephrological conditions. The management is mainly symptomatic
      aiming for pain relief with nonopioid and opioids analgesics, and interventions
      such as capsaicin infusion into the renal pelvis, percutaneous regional nerve
      blocks, and laparoscopic or open surgical procedures, none of them providing
      lasting pain relief. Methods. We describe four cases of LPHS in which long-term
      pain relief was achieved successfully by neuromodulation of lumbar sympathetic
      plexus with implanted electrodes. All patients underwent an initial successful
      trial of neuromodulation with Stimulong monoelectrode (Pajunk, GmbH, Geisingen,
      Germany) inserted percutaneously to lie adjacent to L3-L4 vertebral bodies
      followed by permanent implantation of the stimulation system using four contact
      electrodes (Medtronic Inc, Minneapolis, Minnesota, USA) in two patients with
      excellent long-term pain relief. Results. All our patients had significant
      reductions in visual analog scale scores and analgesic consumption for the
      duration of the monoelectrode trial and in one patient beyond six months. Of the
      two patients who had full implants, pain relief is excellent with minimal
      analgesic consumption and one has resumed employment. There were no
      complications. Discussion. LPHS is very difficult to treat with some experts
      maintaining it is mainly psychological. Conservative treatments are often
      unsatisfactory and radical measures not reliable. Peripheral stimulation of
      nerves and plexuses has been successful as shown from case reports. All our
      patients preferred low-frequency stimulation although its precise mode of action
      is uncertain. Conclusion. Our experience shows that lumbar sympathetic chain
      neuromodulation in intractable LPHS not amenable to conservative therapy is a
      reasonable alternative before radical interventions. More experience is needed in
      multiple centers before its recommendation for refractory LPHS.

PMID- 22151419
TI  - Use of peripheral subcutaneous field stimulation for the treatment of axial neck
      pain: a case report.
AB  - Objective. To present a novel technique of neuromodulation for the treatment of
      axial neck pain. Materials and Methods. A case of a patient with history of long
      standing axial neck pain with previous cervical spine operation and confirmed
      discogenic pain is presented. Traditional treatment measures did not provide
      adequate pain relief. A trial of peripheral subcutaneous field stimulation (PSFS)
      was performed. Following an excellent response during a week-long trial, a
      permanent PSFS system was implanted. The patient was followed for nine months
      after internalization. Results. Seven-day trial of PSFS resulted in complete
      relief of the patient's pain. This 100% relief of pain continued after the
      implantation of permanent PSFS system consisting of two quadripolar electrodes,
      one placed over the paraspinal muscles parallel to midline, and the other
      positioned horizontally over the ipsilateral trapezius muscle. The patient was
      gradually weaned off of all opioid medications and continues to report 100%
      reduction in pain intensity at the nine-month follow-up. Conclusion. PSFS
      represents a new and promising modality in treatment of axial neck pain. Exact
      mechanism of the pain relief remains unclear.

PMID- 22151420
TI  - Facilitation of percutaneous trial lead placement with ultrasound guidance for
      peripheral nerve stimulation trial of ilioinguinal neuralgia: a technical note.
AB  - Introduction. Peripheral nerve stimulation (PNS) has been used for many years to
      treat neuropathic pain syndromes. Technical advances in neurostimulation hardware
      have led to a renewed interest in the use of PNS for control of intractable pain
      caused by peripheral mononeuropathies. One such application includes intractable
      groin pain. This study identified two patients with chronic groin pain, secondary
      to trauma, referred for interventional pain management. For each patient, PNS
      trial was attempted using ultrasound guided localization of the inguinal nerve.
      Direct sonographic visualization of the inguinal nerve has been used in other
      studies to facilitate regional anesthesia, but to our knowledge, no studies have
      used this technique for localization of nerves for percutaneous lead placement
      for PNS. Methods. Each patient was chosen to undergo trial stimulation using
      percutaneously placed peripheral nerve stimulator leads. In these two cases, both
      patients presented with similar complaints of chronic groin pain consistent with
      ilioinguinal neuralgia. Both underwent multiple previous nerve blocks, all of
      which gave good but transient relief using traditional block techniques. Both
      patients were trialed on multiple medications, which either gave incomplete
      relief of pain or were limited by side-effects. Results. Both patients had
      relatively easy localization of ilioinguinal nerves affected using ultrasound and
      were provided with stimulating paresthesias which covered their normal pain.
      Discussion. The successful use of ultrasound as described in these two cases
      suggests an important role for ultrasound in localization of targeted nerves in
      percutaneous trial stimulation of injured peripheral nerve. The use of ultrasound
      may also play a role in permanent lead placement as well. Conclusion. More
      studies are needed to further qualify the role of ultrasound in isolating
      peripheral nerves, but the success of trial stimulation in these two cases holds
      promise for continued advancements in the field of neuromodulation.

PMID- 22151421
TI  - Effect of transcutaneous electrical nerve stimulation on primary dysmenorrhea.
AB  - Objectives. Dysmenorrhea is a disturbing problem among women of childbearing age.
      The purpose of this study is to investigate the effect of high-frequency
      transcutaneous electrical nerve stimulation (TENS) on primary dysmenorrhea and to
      compare the placebo effect by sham TENS in a randomized controlled study.
      Materials and Methods. Twenty-two women participated in the two-month experiment
      by using TENS or sham TENS in a random order for their dysmenorrhea. Outcome
      measures included self-reported pain intensity, symptom and function
      questionnaire related to dysmenorrhea, quality of life, satisfaction after TENS
      application, and other pain management agents adapted by the participants. Two
      way repeated measures analysis of variance (two-way ANOVA) was conducted to
      compare pain intensity between pre-post values and groups (TENS vs. placebo). One
      way repeated measures analysis of variance (one-way ANOVA) was conducted to
      compare scores from questionnaire of symptoms and quality of life at baseline,
      and after placebo or TENS stimulation. Results. Pain intensity in TENS is
      significantly decreased than in the placebo group (p= 0.018). The decrease of
      pain intensity after TENS and placebo TENS were both significant, with p <
      0.00005 and p < 0.00005 respectively. Furthermore, TENS significantly changed the
      degree of autonomic symptoms (p= 0.048); but not after placebo TENS. Conclusion.
      This result supports that women in our country who suffer from primary
      dysmenorrhea could benefit by using TENS, which is consistent with the previous
      studies. In addition to pain-relieving effects, relief of the autonomic symptoms
      associated with dysmenorrhea also indicated that the mechanism of TENS might be
      different from the placebo effect of the sham TENS stimulation. These findings
      indicate the immediate effects of TENS in women with primary dysmenorrheal.

PMID- 22151423
TI  - Response to Kanno et al. "Dorsal Column Stimulation in Persistent Vegetative
      State".

PMID- 22151422
TI  - Normalization of central cord syndrome spinal cord injury urodynamics after
      intrathecal baclofen therapy: a case report.
AB  - Objective. To report a case of improved urodynamics in a central cord syndrome
      spinal cord injury after intrathecal baclofen therapy. Methods. A 47-year-old man
      fell resulting in C4-C5 disc herniation with ventral spinal cord compression and
      cord edema. Results. He underwent an anterior cervical discectomy and fusion.
      Postoperatively, his examination revealed a C4 ASIA D injury in a central cord
      syndrome pattern. Cystometrogram (CMG) revealed a hyperactive detrusor with
      sphincter dyssynergia managed with intermittent self-catheterization. One and a
      half years later, he was impaired by severe lower limb spasticity, despite oral
      medications and botulinum toxin injections. After intrathecal pump therapy, CMG
      revealed relatively normal detrusor and minimal sphincter tone. He volitionally
      voids with urgency but improved continence, which was maintained in one-year
      follow-up. Conclusion. Although the main indication for intrathecal baclofen
      therapy is spasticity, improved urodynamics can be an additional benefit in
      central cord syndrome spinal cord injury.

PMID- 22151424
TI  - Platelet-derived growth factor receptor-alpha cells in mouse urinary bladder: a
      new class of interstitial cells.
AB  - Specific classes of interstitial cells exist in visceral organs and have been
      implicated in several physiological functions including pacemaking and mediators
      in neurotransmission. In the bladder, Kit(+)  interstitial cells have been
      reported to exist and have been suggested to be neuromodulators. More recently a
      second interstitial cell, which is identified using antibodies against platelet
      derived growth factor receptor-alpha (PDGFR-alpha) has been described in the
      gastrointestinal (GI) tract and has been implicated in enteric motor
      neurotransmission. In this study, we examined the distribution of PDGFR-alpha(+) 
      cells in the murine urinary bladder and the relation that these cells may have
      with nerve fibres and smooth muscle cells. Platelet-derived growth factor
      receptor-alpha(+)  cells had a spindle shape or stellate morphology and often
      possessed multiple processes that contacted one another forming a loose network.
      These cells were distributed throughout the bladder wall, being present in the
      lamina propria as well as throughout the muscularis of the detrusor. These cells
      surrounded and were located between smooth muscle bundles and often came into
      close morphological association with intramural nerve fibres. These data describe
      a new class of interstitial cells that express a specific receptor within the
      bladder wall and provide morphological evidence for a possible neuromodulatory
      role in bladder function.

PMID- 22151425
TI  - Knowledge of stroke risk factors and warning signs in Ireland: development and
      application of the Stroke Awareness Questionnaire (SAQ).
AB  - BACKGROUND: Inability to recognize stroke warning signs and delay in seeking
      medical attention for recognized symptoms contribute to treatment delay, thus
      limiting the potential for intervention and impacting negatively on potential
      stroke outcome. AIM: To examine knowledge of stroke risk factors and warning
      signs in the adult population in Ireland. METHODS: In 2009, 1000 members of the
      general public were interviewed by telephone using quota-based population
      sampling of adults (>=18 years). Information was gathered using the Stroke
      Awareness Questionnaire (SAQ). RESULTS: 71% of participants could correctly list
      two or more risk factors for stroke, typically generic lifestyle risk factors.
      Two-thirds could not identify two warning signs for stroke. While 31% could
      identify two or more stroke warning signs, there was no consistency in warning
      signs identified. Less than 50% stated they would call an ambulance if having a
      stroke. Overall, there were significant gaps in knowledge, with poorest levels
      evident in those aged >=65 years. CONCLUSIONS: Survey findings provide first
      evidence on levels of knowledge of stroke risk factors and warning signs in the
      Irish adult population. Awareness of stroke warning signs was poor, as was
      awareness of the need to call emergency services and the potential for acute
      stroke intervention. These factors contribute to delay in seeking medical
      attention following stroke, with resulting implications for stroke outcome.

PMID- 22151426
TI  - Effect of endogen-exogenous melatonin and erythropoietin on dinitrobenzene
      sulfonic acid-induced colitis.
AB  - Inflammatory bowel disease has been linked to elevated T cells. Excessive
      production of reactive oxygen species and apoptosis are known to be accompanied
      by intestinal inflammation. This study was designed to investigate the effects of
      melatonin (MEL) and erythropoietin (EPO), which is a known anti-inflammatory and
      antiapoptotic agent, in dinitrobenzene sulfonic acid (DNBS)-induced colitis in
      pinealectomized (Px) rats. In microscopically results, epithelial and goblet cell
      loss, absence of crypts, and increased colonic caspase-3 activity were observed
      in the DNBS group. Also, in flow cytometric analysis, the percentage of CD4+ T
      cells was highest in the DNBS group. Treatment with MEL or EPO had a curative
      effect on DNBS-induced colitis. The MEL + EPO groups showed significantly greater
      improvement when compared with the other treatment groups. Our results indicate
      that the combination of EPO and MEL may exert more beneficial effects than either
      agent used alone.

PMID- 22151428
TI  - Factors associated with caregiver burden in a child and adolescent psychiatric
      facility in Lagos, Nigeria: a descriptive cross sectional study.
AB  - BACKGROUND: Definitions of burden of care stress the effect of the patient's
      mental illness on the family. There are generally very few studies in this
      environment on caregiver burden in child/adolescent mental ill-health. This study
      aimed to identify patient and caregiver characteristics that are associated with
      caregiver burden. METHOD: Caregivers of patients attending the Child and
      Adolescent Clinic of the Neuropsychiatric Hospital, Yaba, Lagos [n = 155] were
      consecutively recruited over a one-month period. The caregivers were administered
      a sociodemographic questionnaire, the General Health Questionnaire, Zarit Burden
      Interview, and the Columbia Impairment Scale. Scoring on the Children's Global
      Assessment Scale was done by clinicians. RESULTS: Most caregivers observed in
      this study were females (80.5%), with mothers of the patients accounting for 78%
      of all the caregivers. A higher percentage of the patients were males (52.8%).
      Moderate to severe/severe burden was recorded among 25.2% of caregivers. Factors
      associated with caregiver burden were patient's level of functioning [r = 0.489,
      p < 0.001], psychiatric morbidity in the caregiver [r = 0.709, p < 0.001], level
      of impairment as assessed by the caregiver [r = 0.545, p < 0.001], and child's
      level of education [t = 3.274, p = 0.001]. Each one independently predicted
      caregiver burden. CONCLUSION: The study reveals a high level of burden among the
      caregivers of children and adolescents with mental health problems.

PMID- 22151427
TI  - The Enhancer of split complex arose prior to the diversification of schizophoran
      flies and is strongly conserved between Drosophila and stalk-eyed flies
      (Diopsidae).
AB  - BACKGROUND: In Drosophila, the Enhancer of split complex (E(spl)-C) comprises 11
      bHLH and Bearded genes that function during Notch signaling to repress proneural
      identity in the developing peripheral nervous system. Comparison with other
      insects indicates that the basal state for Diptera is a single bHLH and Bearded
      homolog and that the expansion of the gene complex occurred in the lineage
      leading to Drosophila. However, comparative genomic data from other fly species
      that would elucidate the origin and sequence of gene duplication for the complex
      is lacking. Therefore, in order to examine the evolutionary history of the
      complex within Diptera, we reconstructed, using several fosmid clones, the entire
      E(spl)-complex in the stalk-eyed fly, Teleopsis dalmanni and collected additional
      homologs of E(spl)-C genes from searches of dipteran EST databases and the
      Glossina morsitans genome assembly. RESULTS: Comparison of the Teleopsis E(spl)-C
      gene organization with Drosophila indicates complete conservation in gene number
      and orientation between the species except that T. dalmanni contains a duplicated
      copy of E(spl)m5 that is not present in Drosophila. Phylogenetic analysis of
      E(spl)-complex bHLH and Bearded genes for several dipteran species clearly
      demonstrates that all members of the complex were present prior to the
      diversification of schizophoran flies. Comparison of upstream regulatory elements
      and 3' UTR domains between the species also reveals strong conservation for many
      of the genes and identifies several novel characteristics of E(spl)-C regulatory
      evolution including the discovery of a previously unidentified, highly conserved
      SPS+A domain between E(spl)mgamma and E(spl)mbeta. CONCLUSION: Identifying the
      phylogenetic origin of E(spl)-C genes and their associated regulatory DNA is
      essential to understanding the functional significance of this well-studied gene
      complex. Results from this study provide numerous insights into the evolutionary
      history of the complex and will help refine the focus of studies examining the
      adaptive consequences of this gene expansion.

PMID- 22151429
TI  - Does osteomyelitis in the feet of patients with diabetes really recur after
      surgical treatment? Natural history of a surgical series.
AB  - AIMS/HYPOTHESIS: The aim of this study was to determine the rate of recurrence,
      reulceration and new episodes of osteomyelitis and the duration of postoperative
      antibiotic treatment in a prospective cohort of patients with diabetes who
      underwent conservative surgery for osteomyelitis. METHODS: The prospective cohort
      included patients with diabetes and a definitive diagnosis of osteomyelitis who
      were admitted to the Diabetic Foot Unit (Surgery Department, La Paloma Hospital,
      Las Palmas de Gran Canaria, Spain) and underwent surgical treatment from 1
      November 2007 to 30 May 2010. RESULTS: Eighty-one patients were operated on for
      osteomyelitis during the study period. Seven patients were lost to follow-up at
      different stages of the study. The median duration of follow-up was 101.8 weeks
      (quartile 1 = 56.6, quartile 3 = 126.7). Forty-eight patients (59.3%) underwent
      conservative surgery, 32 (39.5%) had minor amputations and there was one (1.2%)
      major amputation. Twenty patients (24.7%) required reoperation because of
      persistent infection. Postoperative antibiotic treatment over a median period of
      36 days was provided. Wound healing was achieved by secondary intention for a
      median of 8 weeks. Sixty-five patients were available for follow-up after
      healing. The percentage of recurrence, reulceration, and new episodes of
      osteomyelitis was 4.6% (3/65), 43% (28/65) and 16.9% (11/65), respectively.
      Mortality during follow-up (excluding in-hospital deaths and patients lost to
      follow-up) was 13% (9/69). CONCLUSION: A low rate of recurrence of osteomyelitis
      after surgical treatment for osteomyelitis was achieved. Despite new episodes,
      our approach to managing this cohort of patients with diabetes and foot
      osteomyelitis achieved 98.8% limb salvage.

PMID- 22151430
TI  - Reduced fracture risk with early corticosteroid withdrawal after kidney
      transplant.
AB  - Corticosteroid use after kidney transplantation results in severe bone loss and
      high fracture risk. Although corticosteroid withdrawal in the early
      posttransplant period has been associated with bone mass preservation, there are
      no published data regarding corticosteroid withdrawal and risk of fracture. We
      hypothesized lower fracture incidence in patients discharged from the hospital
      without than with corticosteroids after transplantation. From the United States
      Renal Data System (USRDS), 77, 430 patients were identified who received their
      first kidney transplant from 2000 to 2006. Fracture incidence leading to
      hospitalization was determined from 2000 to 2007; discharge immunosuppression was
      determined from United Networks for Organ Sharing forms. Time-to-event analyses
      were used to evaluate fracture risk. Median (interquartile range) follow-up was
      1448 (808-2061) days. There were 2395 fractures during follow-up; fracture
      incidence rates were 0.008 and 0.0058 per patient-year for recipients discharged
      with and without corticosteroid, respectively. Corticosteroid withdrawal was
      associated with a 31% fracture risk reduction (HR 0.69; 95% CI 0.59-0.81).
      Fractures associated with hospitalization are significantly lower with regimens
      that withdraw corticosteroid. As this study likely underestimates overall
      fracture incidence, prospective studies are needed to determine differences in
      overall fracture risk in patients managed with and without corticosteroids after
      kidney transplantation.

PMID- 22151431
TI  - Glioblastoma occurring at the site of a previous medulloblastoma following a 5
      year remission period.
AB  - We describe a case of a 14-year-old boy who developed a cerebellar and brainstem
      glioblastoma 5 years after treatment for a medulloblastoma. The patient first
      presented in 2003 with 9 months of vomiting and a 9-kg weight loss. A head MRI
      showed a heterogeneously enhancing posterior fossa mass with hydrocephalus. Gross
      total resection was performed and the tumor was consistent with a classic
      medulloblastoma. Postoperative chemotherapy and craniospinal radiation was
      administered. The patient remained tumor-free until 2008, at which time he
      presented with right-sided weakness and numbness, left eye pain, vomiting and
      weight loss. Imaging showed abnormalities within the posterior pons, medulla,
      inferior cerebellar peduncles, cerebellar hemispheres and cervicomedullary
      junction with expansion of the medulla and cervical spinal cord. Due to the
      location of the lesion, biopsy was felt to be too risky and was avoided. Despite
      receiving chemotherapy, his symptoms continued to worsen and he died 4 months
      later. Post mortem examination limited to the brain and spinal cord confirmed the
      radiographic extent of the tumor. Microscopic examination showed a highly
      cellular infiltrative glial neoplasm with extensive palisading necrosis. A
      diagnosis of glioblastoma was rendered. The question of whether the first and
      second tumors were related is of potential clinical and academic interest. The
      first tumor was synaptophysin-positive and GFAP-negative, consistent with
      medulloblastoma. The second tumor was synaptophysin-negative and focally GFAP
      positive, consistent with glioblastoma. The glioblastoma displayed EGF receptor
      amplification, and interestingly, it also displayed MYCN amplification; both
      tumors showed low level PTEN deletion. The medulloblastoma displayed a signal
      pattern consistent with an isochromosome 17q, while the glioblastoma showed some
      cells with an isochromosome 17q signal pattern amid a background of cells with
      abundant chromosomal instability. The relationship between these two tumors,
      particularly with regard to various molecular events, is discussed.

PMID- 22151432
TI  - A systematic review on the association between genetic predisposition and dental
      implant biological complications.
AB  - OBJECTIVES: The aim of this systematic review was to evaluate the relationship
      between genetic polymorphisms and dental implant biological complications.
      MATERIAL AND METHODS: All prospective, cross-sectional and retrospective studies
      reporting on dental implant loss/peri-implantitis/peri-implant marginal bone loss
      after loading in association with genetic polymorphism were considered for
      inclusion. A thorough search of electronic databases, supplemented by checking
      bibliographies of review articles was performed by two independent reviewers.
      Quality assessment of the included studies was conducted independently and in
      duplicate by two reviewers as part of the data extraction process. RESULTS: The
      search provided 344 related articles. Twenty-two publications were identified for
      possible inclusion and finally, seven articles met the defined inclusion
      criteria. Four studies which investigated the potential relationship between
      early implant loss and IL-1, IL-2, IL-6, TNF-alpha or TGF-beta1 genotype revealed
      no evidence to support this association. In two of the three studies which
      evaluated peri-implantitis in relation to IL-1 genotype, the findings indicate
      that IL-1RN (intron 2), IL-1A (-899), IL-1B (+3954) gene polymorphisms were
      correlated to increased peri-implant tissue infection and destruction.
      CONCLUSIONS: Methodological and study design issues restricted the possibility to
      draw robust conclusions. Within the limits of this review, it might be concluded
      that there is no obvious association between specific genetic polymorphism and
      dental implant failure in terms of biological complications, although a tendency
      should be underlined showing the potential link between IL-1 genotype and peri
      implantitis. Well designed and adequately powered prospective cohort studies are
      needed to provide further information.

PMID- 22151433
TI  - Venous access and care: harnessing pragmatics in harm reduction for people who
      inject drugs.
AB  - AIM: To explore the facilitators of long-term hepatitis C avoidance among people
      who inject drugs. DESIGN: We employed a qualitative life history design. SETTING:
      Recruitment took place through low-threshold drug services and drug user networks
      in South East and North London. Participants were interviewed at the recruitment
      services or in their homes. PARTICIPANTS: The sample comprised 35 people who
      inject drugs, 20 of whom were hepatitis C antibody-negative. Participants'
      average injecting trajectory was 19 years (6-33), with 66% primarily injecting
      heroin, and 34% a crack and heroin mix. Nine (26%) of the sample were female and
      the average age was 39 years (23-53). MEASUREMENTS: Two interviews were conducted
      with each participant, with the second interview incorporating reference to a
      computer-constructed life history time-line. Interview accounts were
      audiorecorded, transcribed verbatim and analysed thematically. FINDINGS:
      Hepatitis C risk awareness was recent and deprioritized by the majority of
      participants. The facilitation of venous access and care was an initial and
      enduring rationale for safe injecting practices. Difficult venous access resulted
      in increased contamination of injecting environments and transitions to femoral
      injecting. Participants expressed an unmet desire for non-judgemental venous
      access information and advice. CONCLUSIONS: Harm reduction interventions which
      attend to the immediate priorities of people who inject drugs, such as venous
      access and care, have the potential to re-engage individuals who are jaded or
      confused by hepatitis C prevention messages.

PMID- 22151434
TI  - Sponge-specific clusters revisited: a comprehensive phylogeny of sponge
      associated microorganisms.
AB  - Marine sponges often contain diverse and abundant communities of microorganisms
      including bacteria, archaea and eukaryotic microbes. Numerous 16S rRNA-based
      studies have identified putative 'sponge-specific' microbes that are apparently
      absent from seawater and other (non-sponge) marine habitats. With more than 7500
      sponge-derived rRNA sequences (from clone, isolate and denaturing gradient gel
      electrophoresis data) now publicly available, we sought to determine whether the
      current notion of sponge-specific sequence clusters remains valid. Comprehensive
      phylogenetic analyses were performed on the 7546 sponge-derived 16S and 18S rRNA
      sequences that were publicly available in early 2010. Overall, 27% of all
      sequences fell into monophyletic, sponge-specific sequence clusters. Such
      clusters were particularly well represented among the Chloroflexi, Cyanobacteria,
      'Poribacteria', Betaproteobacteria and Acidobacteria, and in total were
      identified in at least 14 bacterial phyla, as well as the Archaea and fungi. The
      largest sponge-specific cluster, representing the cyanobacterium 'Synechococcus
      spongiarum', contained 245 sequences from 40 sponge species. These results
      strongly support the existence of sponge-specific microbes and provide a suitable
      framework for future studies of rare and abundant sponge symbionts, both of which
      can now be studied using next-generation sequencing technologies.

PMID- 22151435
TI  - Editorial policy of neuromodulation assures the protection of humans and animals
      used for research.

PMID- 22151436
TI  - Effects on rats of low intensity and frequency electromagnetic field stimulation
      on thoracic spinal neurons receiving noxious cardiac and esophageal inputs.
AB  - Objective  Low intensity and low frequency electromagnetic field stimulation
      (EMFs) provides substantial pain relief in patients with various chronic pains.
      The aim of this study was to examine the effects of EMFs on the activity of
      thoracic spinal neurons responding to noxious visceral stimuli. Materials and
      Methods  Extracellular potentials of single T(3) -T(4)  spinal neurons were
      recorded in pentobarbital anesthetized male rats. A catheter was placed in the
      pericardial sac to administer a mixture of algogenic chemicals for noxious
      cardiac stimulation (0.2 mL, 1 min). Noxious esophageal distension was produced
      by water inflation (0.4 mL, 20 sec) of a latex balloon. EMFs (0.839-0.952 Hz,
      0.030-0.034 uG, 30-40 min) was applied with a pair of Helmholtz coils placed on
      both sides of the chest. Results  After the onset of EMFs, excitatory neuronal
      responses to intrapericardial chemicals were reduced in 24/32 (75%) spinal
      neurons, increased in three neurons and were not affected in five neurons. The
      inhibitory effect on spinal neurons occurred 10-20 min after the onset of EMFs.
      Even after termination of EMFs, the suppression of spinal neuronal activity
      lasted for 1-2 hr. In contrast, excitatory responses of 7/18 (39%) neurons to
      esophageal distension were inhibited, five (28%) were excited and six (33%) were
      not affected by EMFs. Conclusions  Results showed that EMFs generally reduced
      nociceptive responses of spinal neurons to noxious cardiac chemical stimuli,
      whereas it was not effective for nociceptive responses to esophageal mechanical
      stimulation.

PMID- 22151437
TI  - Technical performance of percutaneous leads for spinal cord stimulation: a
      modeling study.
AB  - Objective  To compare the technical performance of different percutaneous lead
      types for spinal cord stimulation. Methods  Using the ut-scs software (University
      of Twente's spinal cord stimulation), lead models having similar characteristics
      such as the 3487A PISCES-Quad (PQ), 3887 PISCES-Quad Compact (PC), 3888 PISCES
      Quad Plus (PP) (Medtronic Inc., Minneapolis, MN), and the AB SC2108 (AB)
      (Advanced Bionics Corp., Valencia, CA) were simulated in monopolar and tripolar
      (guarded cathode) combinations on a single lead, placed just outside the dorsal
      dura mater and both centered on the spinal cord midline, and at 1 mm lateral. The
      influence of displacing a lead dorsally in the epidural fat was examined as well.
      Finally, dual leads both aligned and offset were modeled. Several parameters were
      calculated to allow a quantitative comparison of the performances. Results  When
      programmed as a guarded cathode, the AB lead recruits nerve fibers in an ~25%
      larger dorsal column area than the PQ. However, the AB has an ~160% higher energy
      consumption. The performance of the PC is between the AB and PQ, whereas the PP
      is suitable only for dorsal root stimulation. Displacing a single lead off
      midline or dorsally decreases its ability to recruit fibers in the dorsal
      columns. Similarly, dual lead combinations are less capable when compared to
      single lead centered on the spinal cord midline just outside the dura mater.
      Conclusions  Complex pain syndromes are treated best with lead having a small
      contact spacing, being programmed as a tripole (guarded cathode) and centered on
      the spinal cord midline just outside the dura mater. This is because dorsal
      column fiber recruitment is more extensive than with any other combinations,
      including dual leads. Improved recruitment of dorsal column fibers is accompanied
      by increased energy consumption.

PMID- 22151438
TI  - Sjogren syndrome and spinal cord stimulation: a case report.
AB  - Sjogren syndrome is a chronic autoimmune disease. This disease mainly involves
      salivary and lacrimal glands, although it may also involve the musculoskeletal,
      respiratory, gastrointestinal, renal, hepato-biliary, hematological,
      neurological, vascular, or both systems. Small vessel disease may appear in up to
      30% of the cases. We present a case report of a 62-year-old female diagnosed with
      Sjogren syndrome. Systemic associated manifestations of her disease included
      interstiticial vessel vasculitis with a necrotic, sharp, and painful ulceration
      in her left heel. Because of refractory pain to common analgesic medical
      therapies (paracetamol, metamizol, and tramadol), she was referred to our pain
      unit for evaluation and treatment prior to limb amputation. In our pain unit, a
      percutaneous posterior spinal cord stimulator (SCS) was placed. SCS clinically
      reduced her pain by 90% and helped to improve her quality of life and
      significantly reduced her intake of analgesics. We conclude spinal cord
      stimulation may be a good alternative to conservative therapies in patients with
      vasculitis of Sjogren syndrome.

PMID- 22151439
TI  - Dual spinal cord stimulation for complex pain: preliminary study.
AB  - Objectives  To retrospectively analyze by indices of success, patients with
      chronic complex pain, including, axial low back pain, receiving dual spinal cord
      stimulation (SCS) systems. Methods  Eighteen patients with dual spinal cord
      stimulators have been retrospectively and nonrandomly analyzed. The preponderance
      of patients in our study group had failed back surgery syndrome (FBSS).
      Parameters of success of our therapy included reduction of medication, if any,
      complications, if any, and satisfaction with therapy and improvement in the
      quality of life, measured by a visual analogical scale (VAS) from 0 to 10.
      Patients were asked to rate their overall experience with their SCS systems and
      were divided into four separate groupings according to their overall rating of
      their therapy. These four groupings included therapy ratings of excellent (70
      100%), good (> 50%), fair (< 50%), and poor (< 30%). Satisfaction with therapy
      and improvement in quality of life were evaluated on a five-point scale. Patients
      were asked to rate changes in their quality of life after therapy using the
      following normative scale: much better, better, no change, worse, and much worse.
      All the patients in our study were asked if they would repeat their therapy with
      dual spinal cord stimulation. Results  Paresthesia coverage, overlapping the
      reported painful region, was obtained in 80% of the patients in our study. The
      VAS decreased an average of 5.6 (range 2-10) after 6 months and 4.9 (range 2-8)
      at the end of the study. Six patients (37.5%) reported excellent results; four
      patients (25%) reported good; three (18.7%), fair and poor. Seventy percent of
      the patients were satisfied with the treatment and reported an increase in their
      quality of life. Medications were reduced in 75% of the patients. Thirteen (81%)
      patients with dual lead SCS therapy were willing to repeat the SCS implant
      procedure. Complications occurred in 43.7%. Conclusions  Dual spinal cord
      stimulation is appropriate and efficacious for treating complex pathology and
      complex pain that including pain of the low, axial back.

PMID- 22151440
TI  - Patient selection and trial methods for intraspinal drug delivery for chronic
      pain: a national survey.
AB  - Objectives  Intraspinal drug delivery via indwelling pump is an effective means
      of treating refractory pain. Before a patient is selected for pump implantation,
      an intraspinal drug delivery trial must be performed to establish side-effects
      and efficacy profiles. No consensus protocol currently exists for such trials. As
      a preliminary step in this process, we surveyed a group of interventional pain
      physicians to explore attitudes on patient selection criteria, drug choice, trial
      techniques, and efficacy assessment. Methods  The questionnaire was sent for self
      administration to 1500 interventional pain physicians, each of whom had implanted
      one or more Medtronic((r))  implantable infusion pumps. Results  We received 205
      completed surveys. Among the respondents, most were anesthesiologists (76%) and
      in private practice (82%). Nearly half (45%) of the respondents use the
      continuous intrathecal infusion technique to select patients for permanent
      implants. Conclusions  Trial practices vary widely in terms of patient selection,
      medication choice, technique, and efficacy evaluation. We hope that our findings
      will encourage a concerted effort to evaluate existing trial protocols in order
      to establish a reliable standard of care.

PMID- 22151441
TI  - Clinical protocols for titrating constant flow implantable pumps in patients with
      pain or spasticity.
AB  - Objectives  The objective of this paper is to report the clinical protocols that
      we have developed and used for titrating constant flow implantable pumps to an
      effective dose in de novo pain and spasticity pump patients and, thereby,
      highlight the similarities and differences in our techniques. As a group, we have
      implanted over 1600 pumps and currently manage over 800 pump patients. Materials
      and Methods  We used our collective experience of implanting over 1600 pumps to
      create protocols for performing the drug trial and the initial titration of
      constant flow implantable pumps in de novo patients. Results  In creating our
      protocols, we found that constant flow pumps can be titrated to an effective dose
      with two to six adjustments over a period of 1-6 months. This compares favorably
      to reports of programmable pumps requiring 5.3 +/- 3.5 adjustments over a period
      of 3-6 months to reach an effective dose. Conclusions  A comparison of our
      protocols shows that after an initial stabilization period, dose adjustments can
      be made at subsequent refill, that it is not necessary to adjust the dose by
      prematurely emptying and filling constant flow pumps, and that it is not
      necessary to adjust the dose as often as has been done with programmable pumps.

PMID- 22151442
TI  - Muscular vs. Neural Activation in Propulsion Induced by Electrical Stimulation in
      the Descending Colon of Rats.
AB  - The present experiments were performed on rat colon to study neurogenic and
      myogenic elicited propulsion induced by 0.3 and 30 msec long current pulses. The
      colon segments were stimulated sequentially and randomly. The obtained
      contractions displaced the intraluminal content in individual propulsion steps.
      The propulsion steps differed in displacement onset latency, distance, and
      velocity; the latency decreased while the distance and velocity increased from
      the proximal to the distal colon segments when performing sequential stimulation;
      the propulsion steps differed in latency when stimulation was performed randomly;
      the latency in the first propulsion step was three times longer when using 0.3
      vs. 30 msec long pulses. When inhibiting cholinergic transmission by atropine,
      the propulsion induced by 0.3 msec pulses was blocked, while partially inhibited
      when using 30 msec pulses. Inhibiting nitric oxide synthesis by N(G) -nitro-L
      arginine methyl ester (L-NAME) blocked propulsion induced by both of the pulse
      durations. In conclusion, electrical stimulation induces propulsion when using
      both 0.3 and 30 msec long pulses; stimulation using 0.3 msec pulses activates
      neurons, whereas 30 msec pulses depolarize muscles; in the absence of nitrergic
      transmission, propulsion cannot be induced by electrical stimulation.

PMID- 22151443
TI  - Can the F-Response be Volitionally Repressed during Functional Electrical
      Stimulation?
AB  - Objective  The purpose of this study was to test if the F-response can be
      repressed volitionally. Normally, the F-response is used for clinical diagnostics
      but it also has an important influence on the design of a neural prosthesis
      involving functional electrical stimulation (FES) and the use of volitional
      myoelectric signal (MES) for control. Methods  Ten neurologically normal subjects
      were trained to reduce the level of the F-response from the anterior tibial
      muscle. The nerve to the anterior tibial (TA) muscle was stimulated with constant
      intensity and frequency (16.6 pulses per second) and the surface myoelectric
      signal (MES) from the muscle was digitally processed to estimate the F-level.
      Training was carried out by giving the subject visual feedback on a computer
      screen of the F-level during the stimulation with the task of keeping the level
      as low as possible. Each subject had five sessions consisting of 20 stimulation
      tests, lasting 30 sec each. The subjects acted as their own control and changes
      in the F-level during the stimulation tests, sessions, and trials, were analyzed.
      Results  There was a significant (p < 0.001) increase in the F-response level
      within the test period of constant stimulation, but a significant (p < 0.001)
      decrease from the first to the last test in the session was found. From the first
      to the last session of a trial, the change was found not significant. Conclusion 
      The level of the F-response may change locally, but there is no indication that a
      subject can volitionally learn to repress the response, even when given feedback
      information about the actual level. Therefore the F-waves in the myoelectric
      signal from a stimulated muscle has to be accounted for when designing devices
      using a stimulated muscle response for myoelectric control such as eliminating
      the F-interval from the recorded signal.

PMID- 22151444
TI  - 'Extreme' vasculobiliary injuries: association with fundus-down cholecystectomy
      in severely inflamed gallbladders.
AB  - OBJECTIVES: Extreme vasculobiliary injuries usually involve major hepatic
      arteries and portal veins. They are rare, but have severe consequences, including
      rapid infarction of the liver. The pathogenesis of these injuries is not well
      understood. The purpose of this study was to elucidate the mechanism of injury
      through an analysis of clinical records, particularly the operative notes of the
      index procedure. METHODS: Biliary injury databases in two institutions were
      searched for data on extreme vasculobiliary injuries. Operative notes for the
      index procedure (cholecystectomy) were requested from the primary institutions.
      These notes and the treatment records of the tertiary centres to which the
      patients had been referred were examined. Radiographs from the primary
      institutions, when available, as well as those from the tertiary centres, were
      studied. RESULTS: Eight patients with extreme vasculobiliary injuries were found.
      Most had the following features in common. The operation had been started
      laparoscopically and converted to an open procedure because of severe chronic or
      acute inflammation. Fundus-down cholecystectomy had been attempted. Severe
      bleeding had been encountered as a result of injury to a major portal vein and
      hepatic artery. Four patients have required right hepatectomy and one had
      required an orthotopic liver transplant. Four of the eight patients have died and
      one remains under treatment. CONCLUSIONS: Extreme vasculobiliary injuries tend to
      occur when fundus-down cholecystectomy is performed in the presence of severe
      inflammation. Contractive inflammation thickens and shortens the cystic plate,
      making separation of the gallbladder from the liver hazardous.

PMID- 22151445
TI  - Symptomatic change and gastrointestinal quality of life after pancreatectomy.
AB  - BACKGROUND: Pancreatectomy affects gastrointestinal (GI) symptoms. Our purpose
      was to assess the quality of life of pancreatectomy patients in relation to GI
      function. METHODS: Pancreatectomy patients were asked qualitative, open-ended
      questions about symptoms. They also completed the Gastrointestinal Symptom Rating
      Scale (GSRS) for reflux syndrome, acute pain syndrome, indigestion syndrome,
      diarrhoea syndrome and constipation syndrome. RESULTS: A total of 52 patients
      participated. Of these, 69% reported an improvement and 31% reported no change in
      preoperative symptoms. No patients reported a worsening of symptoms. Half (50%)
      of the patients experienced new, different symptoms. Median GSRS scores were 0
      for reflux syndrome [interquartile range (IQR): 0-1.0], 0 for acute pain syndrome
      (IQR: 0-1.0), 2.0 for indigestion syndrome (IQR: 1.0-4.0), 2.0 for diarrhoea
      syndrome (IQR: 0.5-4.5), and 0 for constipation syndrome (IQR: 0-1.0). Whipple
      operation patients scored higher on the reflux syndrome (0.5 vs. 0; P= 0.08) and
      indigestion syndrome (3.5 vs. 1.5; P= 0.06) domains. A total of 68% of Whipple
      operation patients experienced new symptoms, compared with 32% of patients who
      had undergone other types of pancreatectomy (P= 0.002). Scores of patients who
      had undergone surgery <2 years and >2 years earlier, respectively, did not
      differ. CONCLUSIONS: Patients who underwent pancreatectomy frequently experienced
      an improvement in preoperative symptoms, but also experienced new postoperative
      symptoms. This was more common after Whipple operations. However, these symptoms
      were relatively mild in severity. These mild symptoms seem to persist over time.

PMID- 22151446
TI  - Safety and efficacy of preoperative right portal vein embolization in patients at
      risk for postoperative liver failure following major right hepatectomy.
AB  - BACKGROUND: Right portal vein embolization (RPVE) has been utilized with or
      without segment IV (RPVE + IV) prior to hepatectomy to induce hypertrophy and
      prevent liver insufficiency in patients with a predicted future liver remnant
      (FLR) of <=30% or cirrhosis. METHODS: Records of patients who underwent RPVE
      during 2006-2010 were retrospectively reviewed. Patient demographics, operative
      outcomes and complications were analysed. Computed tomography-based volumetrics
      were performed to determine FLR volume and degree of hypertrophy. Patients were
      stratified by segment IV embolization. Short-term outcomes following RPVE and
      liver resection are reported. RESULTS: A total of 23 patients were identified.
      Ten patients underwent RPVE and 13 underwent RPVE + IV. The RPVE procedure
      resulted in a 38% increase in FLR volume. Liver volumes, hypertrophy rates and
      outcomes were similar in both groups. Rates of operative complications in the
      RPVE and RPVE + IV groups were similar at 50% and 54%, respectively, and most
      complications were minor. Complication rates as a result of embolization were 30%
      in the RPVE group and 31% in the RPVE + IV group. One patient underwent modified
      operative resection as a result of a complication of RPVE. CONCLUSIONS: Right
      portal vein embolization (+/-segment IV) is a safe and effective modality to
      increase FLR volume. Post-embolization complications and short-term outcomes
      after resection are acceptable and are similar in both RPVE and RPVE + IV.

PMID- 22151447
TI  - The role of 18FDG PET/CT in the management of colorectal liver metastases.
AB  - INTRODUCTION: Surgical resection remains the only potentially curative treatment
      for colorectal liver metastases (CLM). However, involvement of both the hepatic
      lobes or extrahepatic disease (EHD) can be a contra-indication for resection. The
      aim of the present study was to examine the addition of combined positron
      emission and computed tomography (PET/CT) to CLM staging to assess the effects
      upon staging and management. METHODS: All CLM patients referred to a single
      centre between January 2005 and January 2009 were prospectively included. All
      underwent routine staging (clinical examination and computed tomography),
      followed by a whole body (18) fluoro-deoxy-glucose ((18)FDG)-PET/CT scan and Fong
      clinical risk score calculation. RESULTS: Sixty-four patients were included [63%
      male with a median age of 63 years (age range 32-79 years)]. The addition of
      PET/CT led to disease upstaging in 20 patients (31%) and downstaging in two
      patients (3%). EHD was found in 24% of low-risk patients (Fong score 0-2) as
      compared with 44% of high-risk patients (Fong score 3-5) (P= 0.133). There was a
      trend towards a greater influence upon management in patients with a low score
      (44% vs. 17%; P= 0.080). CONCLUSION: The addition of PET/CT led to management
      changes in over one-third of patients but there was no correlation between
      alterations in staging or management and the Fong clinical risk score; suggesting
      that PET/CT should be utilized, where available, in the pre-operative staging of
      CLM patients.

PMID- 22151448
TI  - Roux-en-Y drainage of a pancreatic fistula for disconnected pancreatic duct
      syndrome after acute necrotizing pancreatitis.
AB  - BACKGROUND: After acute necrotizing pancreatitis (ANP), a pancreatic fistula may
      occur from disconnected pancreatic duct syndrome (DPDS) where a segment of the
      pancreas is no longer in continuity with the main pancreatic duct. AIM: To study
      the outcome of patients treated using Roux-Y pancreatic fistula tract-jejunostomy
      for DPDS after ANP. METHODS: Between 2002 and 2011, patients treated for DPDS in
      the setting of endoscopic retrograde cholangiopancreatography (ERCP) or magnetic
      resonance cholangiopanreatography (MRCP) documented main pancreatic duct
      disruption with Roux-Y pancreatic fistula tract-jejunostomy. RESULTS: In all,
      seven patients with DPDS were treated. The median age was 62 years (range 49-78)
      and five were men. The cause of ANP was gallstones (2), alcohol (1), ERCP (1) and
      idiopathic (3). Pancreatic necrosectomy was done in six patients. Time from onset
      of pancreatitis to fistula drainage was 270 days (164-365). Pancreatic fistulae
      arose from DPDS in the head/neck (4) and body/tail (3). Patients had a median
      fistula output of 140 ml (100-200) per day before surgery. The median operative
      time was 142 min (75-367) and estimated blood loss was 150 ml (25 to 500).
      Patients began an oral diet on post-operative day 4 (3-6) and were hospitalized
      for a median of 7 days (5-12). The median follow-up was 264 days (29-740).
      Subsequently, one patient required a distal pancreatectomy. After surgery, three
      patients required oral hypoglycaemics. No patient developed pancreatic exocrine
      insufficiency. CONCLUSION: Internal surgical drainage using Roux-en-Y pancreatic
      fistula tract-jejunostomy is a safe and definitive treatment for patients with
      DPDS.

PMID- 22151449
TI  - Vascular architecture in anomalous right-sided ligamentum teres: three
      dimensional analyses in 35 patients.
AB  - BACKGROUND: Right-sided ligamentum teres (RSLT) is a congenital anomaly that is
      sometimes encountered during hepatobiliary surgeries. However, a valid protocol
      for describing the segmental anatomy of livers with RSLT has not been
      established, and confusions or anatomic misunderstandings have been a major
      problem. METHODS: The vascular architecture and morphological characteristics
      were investigated in 35 livers with RSLT using three-dimensional (3D)
      simulations. RESULTS: Couinaud's four sectors and three hepatic veins were
      clearly distinguished in the liver with RSLT using 3D simulations. The ligamentum
      teres was connected with the right paramedian portal pedicle, and the long axis
      of the cystic fossa was always observed on the left of the ligamentum teres in
      all 35 livers. However, when the main portal scissura was visualized using 3D
      simulation, the gallbladder was always located on the border of either side of
      the hemilivers, and the malposition of the gallbladder was not confirmed.
      CONCLUSIONS: Although the right-sided components of the livers are well developed
      as a result of the right-dominant distribution of the feeding vessels in livers
      with RSLT, the basic segmental structure defined by the four sectors and the
      three hepatic veins are as well preserved as those in the typical liver anatomy.

PMID- 22151450
TI  - Utilization of hepatitis B core antibody-positive donor liver grafts.
AB  - BACKGROUND: The inclusion of hepatitis B core antibody-positive (HBcAb+) liver
      donors is a strategy utilized to increase organ availability. This study examined
      HBcAb+ transplantation practices to identify specific factors influencing
      outcomes. METHODS: Twenty-five HBcAb+ liver transplants were identified
      retrospectively among 868 adult transplants performed between 1 January 1997 and
      31 December 2009. Twelve (48%) recipients had hepatitis C and five (20%) had
      hepatitis B. Patient and donor demographics, preoperative morbidity, transplant
      data and outcomes were examined. Statistical analysis was completed using
      Student's t-test or the Kaplan-Meier method. A P-value of <0.05 was considered
      significant. RESULTS: There was no difference in age, body mass index or
      comorbidities between HBcAb+ liver recipients and control subjects. Model for End
      stage Liver Disease (MELD) scores of >30 were significantly more frequent in
      HBcAb+ liver recipients (32% vs. 15%; P= 0.04). All patients received
      immunoglobulin and longterm antiviral therapy as prophylaxis against graft
      hepatitis B resurgence. No patients who received HBcAb+ livers developed
      hepatitis B infection on follow-up. Overall survival at 30 days, 1 year and 5
      years in HBcAb+ liver recipients was 92%, 74% and 74%, respectively, compared
      with 96%, 89% and 76%, respectively, in the control group (P= not significant,
      log-rank test). All except one of the deaths in the HBcAb+ liver recipient group
      occurred within 90 days postoperatively and in patients with MELD scores >30.
      CONCLUSIONS: The practice of transplanting HBcAb+ grafts incurs low risk for
      infection using current methods of prophylaxis. The highest mortality risk was in
      the early postoperative period, specifically in patients with very high MELD
      scores. This probably reflects the practice of using positive serology grafts in
      emergent situations.

PMID- 22151451
TI  - Biliary complications after right lobe living donor liver transplantation: a
      single-centre experience.
AB  - BACKGROUND: Biliary complications that developed after right lobe liver
      transplantation from living donors were studied in a single centre. METHODS: From
      2004 to 2010, 200 consecutive living donor right lobe liver transplantations were
      performed. The database was evaluated retrospectively. Biliary complications were
      diagnosed according to clinical, biochemical and radiological tests. The number
      of biliary ducts in the transplanted graft, the surgical techniques used for
      anastomosis, biliary strictures and bile leakage rates were analysed. RESULTS: Of
      a total of 200 grafts, 117 invloved a single bile duct, 77 had two bile ducts and
      in six grafts there were three bile ducts. In 166 transplants, the anastomosis
      was performed as a single duct to duct, in 21 transplants double duct to ducts,
      in one transplant, three duct to ducts and in 12 transplants as a Roux-en-Y
      reconstruction. In all, 40 bile leakages (20%) and 17 biliary strictures (8.5%)
      were observed in 49 patients resulting in a total of 57 biliary complications
      (28.5%). Seventeen patients were re-operated (12 as a result of bile leakages and
      five owing to biliary strictures). CONCLUSION: Identification of more than one
      biliary orifice in the graft resulted in an increase in the complication rates.
      In grafts containing multiple orifices, performing multiple duct-to-duct (DD) or
      Roux-en-Y anastomoses led to a lower number of complications.

PMID- 22151452
TI  - Route of gastroenteric reconstruction in pancreatoduodenectomy and delayed
      gastric emptying.
AB  - BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after
      pancreatoduodenectomy. Some previous studies suggest that antecolic (compared
      with retrocolic) gastroenteric reconstruction lowers the incidence of DGE. The
      present study was performed to investigate the relation between the route of
      gastroenteric reconstruction and DGE after pancreatoduodenectomy. METHODS: In a
      consecutive series of pancreatoduodenectomies, the route of gastroenteric
      reconstruction was retrospectively determined. Hospital course was prospectively
      recorded. Patients with antecolic and retrocolic reconstruction were compared.
      Primary outcome was DGE (ISGPS definition). Secondary outcomes were other
      complications and hospital stay. RESULTS: Of 154 included patients, 50% had
      retrocolic reconstruction. DGE occurred in 58% of retrocolic patients, vs 52% of
      antecolic patients (NS). 'Primary' DGE (without other intra-abdominal
      complications) occurred in 36% (retrocolic) and 20% (antecolic) (P= 0.02) of the
      patients. In multivariable analysis, the route of reconstruction was not
      associated with primary DGE. Clinically relevant primary DGE (grade B/C) did not
      differ, nor did the secondary outcomes. DISCUSSION: The incidence of DGE did not
      differ between the study groups. 'Primary' DGE was more frequent in the
      retrocolic group, but in multivariable analysis, no association between the route
      of reconstruction and primary DGE was found. The preferred route for
      gastroenteric reconstruction after pancreatoduodenectomy remains to be
      investigated in a well-powered, randomized, controlled trial.

PMID- 22151453
TI  - Predictors of response to radio-embolization (TheraSphere(r)) treatment of
      neuroendocrine liver metastasis.
AB  - BACKGROUND: Neuroendocrine tumours (NET) frequently metastasize to the liver. NET
      liver metastasis has been shown to respond to Yttrium-90 microspheres therapy.
      The aims of the present study were to define factors that predict the response to
      radio-embolization in patients with NET liver metastases. METHODS: From January
      2006 until March 2009, all patients with NET liver metastasis that received radio
      embolization using TheraSphere(r) (glass microspheres) were reviewed. The
      response was determined by a change in the percentage of necrosis (DeltaN%) after
      the first radio-embolization based on the modified RECIST criteria (mRECIST)
      criteria. The following confounding variables were measured: age, gender, size of
      the lesions, liver involvement, World Health Organization (WHO) classification,
      the presence of extra-hepatic metastasis, octereotide treatment and previous
      operative [surgery and (RFA)] and non-operative treatments (chemo-embolization
      and bland-embolization). RESULTS: In all, 25 patients were identified, with a
      median follow-up of 21.7 months. The median age was 64.6 years, 28% had extra
      hepatic metastasis and 56% were WHO stage 2. Post-treatment, the mean DeltaN% was
      48.4%. Previous surgical therapy was a significant predictor of the response with
      a response rate of 66.7 DeltaN% vs. 31.5 DeltaN% (P= 0.02). Bilateral liver
      disease, a high percentage of liver involvement and large metastatic lesions were
      inversely related to the degree of tumour response although did not reach
      statistical significance. CONCLUSION: Radio-embolization increased the necrosis
      of NET liver metastasis mainly in patients with less bulky disease. This may
      imply that surgical therapy before radio-embolization would increase the response
      rates.

PMID- 22151454
TI  - Hepatic artery reconstruction first for the treatment of hilar cholangiocarcinoma
      bismuth type IIIB with contralateral arterial invasion: a novel technical
      strategy.
AB  - BACKGROUND: En-bloc liver resection with the extrahepatic bile duct is mandatory
      to obtain tumour-free surgical margins and better long-term outcomes in hilar
      cholangiocarcinoma (CC). One of the most important criteria for irresectability
      is local extensive invasion to major vessels. As hilar CC Bismuth type IIIB often
      requires a major left hepatic resection, the invasion of the right hepatic artery
      (RHA) usually contraindicates this procedure. METHODS: The authors describe a
      novel technique that allowed an oncological resection in two patients with hilar
      CC Bismuth type IIIB and contralateral arterial invasion. Arterial reconstruction
      between the posterior branch of the RHA and the left hepatic artery (LHA) was
      performed as the first surgical step. Once arterial vascular flow was restored, a
      left trisectionectomy with caudate lobe resection and portal vein reconstruction
      was performed. RESULTS: In both patients an R0 resection was achieved. Both
      patients made a full recovery and were discharged within 14 days of surgery. Both
      patients remain free of disease at 18 months. CONCLUSIONS: This new technique
      allows a R0 resection to be achieved in patients with Bismuth type IIIB hilar CC
      with contralateral arterial involvement.

PMID- 22151455
TI  - Total bilirubin is a good discriminator between benign and malignant biliary
      strictures.

PMID- 22151457
TI  - Treatment of meralgia paresthetica with ultrasound-guided pulsed radiofrequency
      ablation of the lateral femoral cutaneous nerve.
AB  - A 23-year-old female with an 18-month history of left anterolateral thigh
      paresthesias and burning pain consistent with meralgia paresthetica was referred
      to our clinic after failing trials of physical therapy, nonsteroidal anti
      inflammatories, gabapentin, and amitriptyline. We performed 3 lateral femoral
      cutaneous nerve blocks with corticosteroid over a 4-month period; however, each
      block provided only temporary relief. As this pain was limiting the patient's
      ability to perform her functions as an active duty service member, we elected to
      perform a pulsed radiofrequency treatment of the lateral femoral cutaneous nerve
      with ultrasound guidance and nerve stimulation. After locating the lateral
      femoral cutaneous nerve with ultrasound and reproducing the patient's dysthesia
      with stimulation, pulsed radiofrequency treatment was performed at 42 degrees C
      for 120 seconds. The needle was then rotated 180 degrees  and an additional cycle
      of pulsed radiofrequency treatment was performed followed by injection of 0.25%
      ropivacaine with 4 mg of dexamethasone. At 1.5 and 3 month follow-up visits, the
      patient reported excellent pain relief with activity and improved ability to
      perform her duties as an active duty service member. ?

PMID- 22151459
TI  - Education: the goal of the next decade.

PMID- 22151460
TI  - Effects of spinal cord stimulation on nutritional skin blood flow in patients
      with ischemic pain.

PMID- 22151458
TI  - Proinflammatory cytokine levels in hyperlipidemic patients with periodontitis
      after periodontal treatment.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of periodontal
      treatment on serum and gingival crevicular fluid (GCF) proinflammatory cytokine
      levels in hyperlipidemic patients with periodontitis. MATERIALS AND METHODS:
      Fifty-two patients with hyperlipidemia and periodontitis and 28 systemically
      healthy controls with periodontitis (C) were included in the study.
      Hyperlipidemic groups were divided into two groups as suggested diet (HD) and
      prescribed statin (HS). The clinical periodontal parameters, fasting venous
      blood, and GCF samples were obtained, and serum tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL) 1-beta, and IL-6 levels were evaluated at baseline and
      at 3 months follow-up (3MFU) after the completion of the non-surgical periodontal
      treatment that included scaling and root planning. RESULTS: Percentage of
      bleeding on probing was significantly higher in the HS group than both the HD and
      C groups. In the HD and HS groups, there were significant decreases in serum IL-6
      and GCF TNF-alpha levels between the 3MFU and baseline. A significant decrease
      was also found in GCF IL-6 at the end of the study period in the HS group.
      CONCLUSION: The combination of the periodontal therapy and antilipemic treatment
      may provide beneficial effects on the metabolic and inflammatory control of
      hyperlipidemia.

PMID- 22151461
TI  - Spinal cord stimulation in severe, inoperable peripheral vascular disease.
AB  - Objective. To assess the effect of spinal cord stimulation in patients with
      severe, inoperable peripheral vascular disease, and uncontrolled pain. Patients
      and methods. A case study of 20 patients with end-stage peripheral vascular
      disease, either Fontaine Class 3 or 4 limb ischemia. All 20 patients implanted
      with spinal cord stimulation devices with follow-up from one to five years (mean,
      32 months) performed in a multidisciplinary pain treatment center. Results. In
      the 20 patients implanted with a spinal cord stimulator for peripheral vascular
      disease, overall there was 75% limb salvage; with Fontaine Class 3 patients there
      was 86% and with Fontaine Class 4 patients, 69% limb salvage of the treated
      limbs. Conclusions. Twenty patients with end-stage peripheral vascular disease
      were implanted with spinal cord stimulators and followed for five years, until
      amputation or end of life, showing excellent results for limb salvage and minimal
      complications. The current literature regarding the use of spinal cord
      stimulation for peripheral vascular disease is reviewed, supporting its benefit
      for limb salvage and pain relief.

PMID- 22151462
TI  - Effect of spinal cord stimulation on sensory nerve conduction threshold
      functional measures.
AB  - Background. Spinal cord stimulation (SCS) is being used with increasing frequency
      in the treatment of various chronic pain conditions. There is a paucity of
      reliable outcome data regarding changes in pain tolerance and peripheral sensory
      nerve function. The automated electrodiagnostic neuroselective sensory Nerve
      Conduction Threshold (sNCT) test measures painless current perception thresholds
      (CPTs) and atraumatic pain tolerance thresholds (PTTs). The ability of the sNCT
      test to independently evaluate small and large fiber function may have particular
      relevance for evaluating response to SCS. Methods/Results. Sixteen patients with
      implanted SCS systems and lower extremity neuropathic pain of greater than 6
      months duration were tested using a standardized protocol, pre- and post-SCS. CPT
      and PTT measures (Neurometer, CPT/C Neurotron, Inc. Baltimore, MD) were obtained
      from the distal phalange of the most symptomatic extremity and at an ipsilateral
      asymptomatic control site. Only CPTs at the symptomatic site (2000 Hz only) and
      at the control site (5 Hz only) reached statistical significance. Changes in CPTs
      at other frequencies, and changes in PTTs at all frequencies (symptomatic and
      control sites) were not statistically significant. Conclusion. The results of
      this study appear to substantiate the postulates that both segmental and
      suprasegmental effects are involved in SCS-mediated analgesia. SCS modulates
      segmental large afferent fiber input as reflected by a statistically significant
      increase in large fiber CPTs (2000 Hz) at the symptomatic site post-SCS. A
      statistically significant increase in small fiber (5 Hz) CPTs at the control site
      suggests a central sensory (suprasegmental) modulating effect on nociceptive
      fiber activity. sNCT testing provided reliable outcome data for evaluating
      response to SCS.

PMID- 22151463
TI  - Spinal cord stimulation for post-herniorrhaphy pain.
AB  - Objective. Post-herniorrhaphy pain syndrome can be difficult to treat. The exact
      mechanism of pain is not always apparent. Multiple therapeutic modalities have
      been suggested for the treatment of this syndrome. Method. This includes both
      conservative (medical management), surgical (scar revision, excision of neuroma),
      and/or interventional approaches (local blocks to the entrapped nerves or
      sympathetic ganglion). Results. Two cases of intractable post-herniorrhaphy pain
      syndrome which failed to respond to conservative therapy are reviewed. Both cases
      had a successful trial therapy with spinal cord stimulation for their pain. Both
      then had permanent implantable systems inserted with favorable outcomes.
      Conclusion. Post-herniorrhaphy pain can have the same features of both
      nociceptive and neuropathic pain syndromes. In cases which have failed
      conservative therapy we believe that a trial of spinal cord stimulation is
      warranted as in other cases of neuropathic pain syndromes.

PMID- 22151464
TI  - Letter to the editor.

PMID- 22151465
TI  - Visual prostheses: a review.
AB  - An area of recent interest is the development of a visual prosthesis by
      electrically stimulating neural tissue of blind patients. Major efforts in this
      area include electrode arrays implanted on or under the retina, around the optic
      nerve, and on or in the visual cortex. On February 19, 2000, the Alfred E. Mann
      Institute for Biomedical Engineering at University of Southern California (Los
      Angeles, CA) held a symposium which brought together experts from across the US
      to discuss the state of the art in this research area. This review article gives
      historical background in the field and summarizes the presentations from this
      meeting.

PMID- 22151466
TI  - FES Rehabilitative Systems for Re-Education of Walking in Incomplete Spinal Cord
      Injured Persons.
AB  - Objective. The aim of the paper is to present various relatively simple
      functional electrical stimulation (FES) systems that affect neural circuits and
      reflex behavior by providing necessary peripheral input to the lower extremities
      of incomplete spinal cord injured (SCI) persons. Methods. The proposed FES re
      education walking systems make use of feedback information that is transmitted
      from the paralyzed limb to the nonparalyzed part of the patient's body. A single
      gait variable can be analogously transmitted to the walking subject in a form of
      sensory stimulation. The information about several gait variables can be first
      integrated and afterwards delivered to the walking subject as a single command.
      Conclusions. Significant improvements in the duration of the double support
      phase, metabolic energy expenditure, and physiologic cost index were observed
      when using FES-assisted training of walking in incomplete SCI persons.

PMID- 22151467
TI  - Spinal cord stimulation surgical technique for the nonsurgically trained.
AB  - The objective of this paper is to educate physicians who implant spinal cord
      stimulators in current surgical techniques. Many implanters have not gone through
      formal surgical residencies and learn their surgical techniques during a one year
      Fellowship or from proctoring experience. This paper utilizes current concepts
      from the literature to reinforce appropriate surgical practices, which are
      applicable to surgeons as well as interventional pain physicians. This should be
      a valuable resource for all Fellows whether they are in surgical programs or pain
      fellowship programs. In addition, a more detailed presentation is made at the end
      of this paper on a proposed simple one-incision surgical technique for
      implantation of small internal pulse generators. This is the first publication in
      the literature describing such a technique and may be useful for less-experienced
      implanters, as well as conferring potential advantages in surgical technique.

PMID- 22151468
TI  - Idiopathic immune-mediated thrombocytopenia and recent vaccination in dogs.
AB  - BACKGROUND: Vaccination is often cited as a potential cause of immune-mediated
      thrombocytopenia (ITP) in dogs. Although an association has been documented in
      humans, particularly in children, this relationship has not been definitively
      established in dogs. OBJECTIVES: To identify the presence of an association
      between recent vaccination and ITP in dogs. ANIMALS: Forty-eight client-owned
      dogs with presumptive idiopathic ITP and 96 age-matched, client-owned dogs with
      non-immune-mediated disease. METHODS: Retrospective, case-control study. Dogs
      were identified through the Veterinary Medical Database (VMDB) and Hospital
      Information System at Purdue University. RESULTS: The median age at presentation
      for dogs with ITP was 7 years (range: 2-15 years). The majority of the ITP group
      was comprised of mixed breed dogs (38%); no pure breed was represented by more
      than 3 cases. The number of dogs that were vaccinated within 42 days of diagnosis
      of ITP did not differ significantly (P = .361) between cases of presumptive ITP
      (4/48, 8%) and the control group (13/96, 14%). CONCLUSIONS AND CLINICAL
      IMPORTANCE: This study failed to confirm the presence of an association between
      presumptive idiopathic ITP in dogs and recent vaccination; however, the
      possibility of an association cannot be completely ruled out based on the small
      sample populations and requires further investigation.

PMID- 22151469
TI  - SPREAD-STACI study: a protocol for a randomized multicenter clinical trial
      comparing urgent with delayed endarterectomy in symptomatic carotid artery
      stenosis.
AB  - RATIONALE: In patients with >50% carotid artery stenosis (as measured by North
      American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria) suffering a
      transient ischemic attack or a minor ipsilateral stroke, carotid endarterectomy
      exerts maximum benefits, when performed within the first 15 days from the initial
      ischemic symptom. It is also known that the probability of a major stroke spikes
      within the first few days after a transient ischemic attack/minor stroke and then
      flattens out in the following days and weeks. It could be hypothesized that
      urgent carotid endarterectomy has greater benefit than delayed procedure. AIMS:
      Demonstrate that urgent carotid endarterectomy is more effective than delayed
      interventions. DESIGN: Centers employing neurolgist/stroke physicians and
      vascular surgeons will enroll TIA or minor stroke patients with >50 % carotid
      artery stenosis (Nascet criteria), randomized in two groups: urgent carotid
      endarterectomy (within 48 hours) and delayed carotid endarterectomy ( operated
      between 48 hours and 15 days after onset of symptoms) Risk factors will be
      evaluated at enrollment. TIA will be classified by ABCD2 scoring system,and minor
      stroke by National Institutes of Health Stroke Scale (NIHSS) scores. The study
      will last 90 days per patient,starting from their initial symptom,and the follow
      up will be performed by an indipendent neurologist. A total of 456 patients (228
      / group) is needed to observe an absolute difference of 10% between groups.
      OUTCOMES: Primary end-point is reduction in all types of stroke, AMI or death in
      urgent endarterectomy groupo compared to delayed ones. Secondary end-points are:
      Reduction of ipsilateral ischemic stroke in group 1 with respect to Group 2
      Identification of predictive risk factors and Confirmation of no different rate
      for hemorragic/ischemiccomplications between groups.

PMID- 22151470
TI  - Accelerated large-scale multiple sequence alignment.
AB  - BACKGROUND: Multiple sequence alignment (MSA) is a fundamental analysis method
      used in bioinformatics and many comparative genomic applications. Prior MSA
      acceleration attempts with reconfigurable computing have only addressed the first
      stage of progressive alignment and consequently exhibit performance limitations
      according to Amdahl's Law. This work is the first known to accelerate the third
      stage of progressive alignment on reconfigurable hardware. RESULTS: We reduce
      subgroups of aligned sequences into discrete profiles before they are pairwise
      aligned on the accelerator. Using an FPGA accelerator, an overall speedup of up
      to 150 has been demonstrated on a large data set when compared to a 2.4 GHz Core2
      processor. CONCLUSIONS: Our parallel algorithm and architecture accelerates large
      scale MSA with reconfigurable computing and allows researchers to solve the
      larger problems that confront biologists today. Program source is available from
      http://dna.cs.byu.edu/msa/.

PMID- 22151471
TI  - Antiviral therapy for recurrent hepatitis C reduces recurrence of hepatocellular
      carcinoma following liver transplantation.
AB  - Recurrence of hepatocellular carcinoma (HCC) is one of the major concerns
      following liver transplantation (LT). With the potential antitumor properties of
      interferon (IFN), their role in prevention of HCC recurrence is to be defined. We
      retrospectively reviewed 46 patients who underwent LT for hepatitis C virus (HCV)
      related HCC between January 2004 and December 2008. Twenty-four (52.2%) patients
      with biopsy-proven HCV recurrence received antiviral therapy (IFN group); their
      outcomes were compared with 22 patients (control group). There was no significant
      difference for tumor size, number, and type of neo-adjuvant therapy between the
      two groups. The 1- and 3-year overall patient survival (100% vs. 90.9% and 87.3%
      vs. 71.8%; P = 0.150) and tumor-free survival (100% vs. 72.7% and 83.1% vs.
      67.5%; P = 0.214) between IFN and control group were comparable. HCC recurrence
      was the most common cause of death (n = 6 of 12, 50%), all in the control group.
      During follow-up, seven (15.2%) patients developed HCC recurrence: one (4.1%) in
      the IFN group and six (27.3%) in the control group (P < 0.05). In conclusions,
      HCC recurrence rate and related deaths were significantly lower in patients that
      received post-transplant antiviral therapy for recurrent HCV.

PMID- 22151472
TI  - Medication administration errors for older people in long-term residential care.
AB  - BACKGROUND: Older people in long-term residential care are at increased risk of
      medication prescribing and administration errors. The main aim of this study was
      to measure the incidence of medication administration errors in nursing and
      residential homes using a barcode medication administration (BCMA) system.
      METHODS: A prospective study was conducted in 13 care homes (9 residential and 4
      nursing). Data on all medication administrations for a cohort of 345 older
      residents were recorded in real-time using a disguised observation technique.
      Every attempt by social care and nursing staff to administer medication over a 3
      month observation period was analysed using BCMA records to determine the
      incidence and types of potential medication administration errors (MAEs) and
      whether errors were averted. Error classifications included attempts to
      administer medication at the wrong time, to the wrong person or discontinued
      medication. Further analysis compared data for residential and nursing homes. In
      addition, staff were surveyed prior to BCMA system implementation to assess their
      awareness of administration errors. RESULTS: A total of 188,249 medication
      administration attempts were analysed using BCMA data. Typically each resident
      was receiving nine different drugs and was exposed to 206 medication
      administration episodes every month. During the observation period, 2,289
      potential MAEs were recorded for the 345 residents; 90% of residents were exposed
      to at least one error. The most common (n = 1,021, 45% of errors) was attempting
      to give medication at the wrong time. Over the 3-month observation period, half
      (52%) of residents were exposed to a serious error such as attempting to give
      medication to the wrong resident. Error incidence rates were 1.43 as high (95% CI
      1.32-1.56 p < 0.001) in nursing homes as in residential homes. The level of non
      compliance with system alerts was very low in both settings (0.075% of
      administrations). The pre-study survey revealed that only 12/41 staff
      administering drugs reported they were aware of potential administration errors
      in their care home. CONCLUSIONS: The incidence of medication administration
      errors is high in long-term residential care. A barcode medication administration
      system can capture medication administration errors and prevent these from
      occurring.

PMID- 22151473
TI  - Intermittent hypobaric hypoxia applicability in myocardial infarction prevention
      and recovery.
AB  - Intermittent hypobaric hypoxia (IHH) has been the focus of important research in
      cardioprotection, and it has been associated with several mechanisms.
      Intermittent hypobaric hypoxia inhibits prolyl hydroxylases (PHD) activity,
      increasing the stabilization of hypoxia-inducible factor-1 (HIF-1) and activating
      crucial adaptative genes. It has been hence suggested that IHH might be a simple
      intervention, which may offer a thoughtful benefits to patients with acute
      myocardial infarction and no complications. Nevertheless, several doubts exist as
      to whether IHH is a really safe technique, with little to no complications in
      post-myocardial infarction patients. Intermittent hypobaric hypoxia might produce
      instead unfavourable changes such as impairment of vascular hemodynamics and
      hypertensive response, increased risk of hemoconcentration and thrombosis,
      cardiac rhythm perturbations, coronary artery disease and heart failure, insulin
      resistance, steatohepatitis and even high-altitude pulmonary oedema in
      susceptible or nonacclimatized patients. Although intermittent and chronic
      exposures seem effective in cardioprotection, IHH safety issues have been mostly
      overlooked, so that assorted concerns should be raised about the opportunity to
      use IHH in the post-myocardial infarction period. Several IHH protocols used in
      some studies were also aggressive, which would hamper their widespread
      introduction within the clinical practice. As such, further research is needed
      before IHH can be widely advocated in myocardial infarction prevention and
      recovery.

PMID- 22151475
TI  - Motion style acupuncture treatment (MSAT) for acute low back pain with severe
      disability: a multicenter, randomized, controlled trial protocol.
AB  - BACKGROUND: Acupuncture is widely-used to treat patients with low back pain,
      despite insufficient evidence of the technique's efficacy for acute back pain.
      Motion style acupuncture treatment (MSAT) is a non-traditional acupuncture
      treatment requiring a patient to exercise while receiving acupuncture. In Korea,
      MSAT is used to reduce musculoskeletal pain and improve functional status. The
      study aims to evaluate the effect of MSAT on acute low back pain with severe
      disability. METHODS/DESIGN: This study is a multicenter, randomized, active
      controlled trial with two parallel arms. Participants with acute low back pain
      and severe functional disability, defined as an Oswestry Disability Index (ODI)
      value > 60%, will be randomly allocated to the acupuncture group and the
      nonsteroidal anti-inflammatory drug (NSAID) injection group. The acupuncture
      group will receive MSAT and the NSAID injection group will receive an
      intramuscular injection of diclofenac. All procedures will be limited to one
      session and the symptoms before and after treatment will be measured by assessors
      blinded to treatment allocation. The primary outcome will be measured at 30
      minutes after treatment using the numerical rating scale (NRS) of low back pain
      while the patient is moving. Secondary outcomes will be measured at 30 minutes
      after treatment using the NRS of leg pain, ODI, patient global impression of
      change, range of motion (ROM) of the lumbar spine, and degrees of straight leg
      raising (SLR). Post-treatment follow-up will be performed to measure primary and
      secondary outcomes with the exception of ROM and SLR at 2, 4, and 24 weeks after
      treatment. DISCUSSION: The results of this trial will be discussed. TRIAL
      REGISTRATION: ClinicalTrial.gov NCT01315561.

PMID- 22151476
TI  - Effect of intravitreal cell-based produced glucagon-like peptide-1 on Bcl and BAX
      expression in the optic nerve crush model.

PMID- 22151477
TI  - Effect of a vitamin/mineral supplement on children and adults with autism.
AB  - BACKGROUND: Vitamin/mineral supplements are among the most commonly used
      treatments for autism, but the research on their use for treating autism has been
      limited. METHOD: This study is a randomized, double-blind, placebo-controlled
      three month vitamin/mineral treatment study. The study involved 141 children and
      adults with autism, and pre and post symptoms of autism were assessed. None of
      the participants had taken a vitamin/mineral supplement in the two months prior
      to the start of the study. For a subset of the participants (53 children ages 5
      16) pre and post measurements of nutritional and metabolic status were also
      conducted. RESULTS: The vitamin/mineral supplement was generally well-tolerated,
      and individually titrated to optimum benefit. Levels of many vitamins, minerals,
      and biomarkers improved/increased showing good compliance and absorption.
      Statistically significant improvements in metabolic status were many including:
      total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003),
      reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced
      glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP
      (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most
      of these metabolic biomarkers improved to normal or near-normal levels.The
      supplement group had significantly greater improvements than the placebo group on
      the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and
      on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall
      (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment
      tools the difference between treatment group and placebo group was not
      statistically significant.Regression analysis revealed that the degree of
      improvement on the Average Change of the PGI-R was strongly associated with
      several biomarkers (adj. R2 = 0.61, p < 0.0005) with the initial levels of biotin
      and vitamin K being the most significant (p < 0.05); both biotin and vitamin K
      are made by beneficial intestinal flora. CONCLUSIONS: Oral vitamin/mineral
      supplementation is beneficial in improving the nutritional and metabolic status
      of children with autism, including improvements in methylation, glutathione,
      oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had
      significantly greater improvements than did the placebo group on the PGI-R
      Average Change. This suggests that a vitamin/mineral supplement is a reasonable
      adjunct therapy to consider for most children and adults with autism. TRIAL
      REGISTRATION:  CLINICAL TRIAL REGISTRATION NUMBER: NCT01225198.

PMID- 22151478
TI  - Abstinence-contingent recovery housing and reinforcement-based treatment
      following opioid detoxification.
AB  - AIMS: To conduct a randomized, controlled trial of abstinence-contingent recovery
      housing delivered with or without intensive day treatment among individuals
      exiting residential opioid detoxification. DESIGN: Random assignment to one of
      three conditions: recovery housing alone (RH), abstinence-contingent recovery
      housing with reinforcement-based treatment RBT (RH + RBT) or usual care (UC). RH
      and RH + RBT participants received 12 weeks of paid recovery housing contingent
      upon drug abstinence. RH + RBT participants also received 26 weeks of RBT,
      initiated concurrently with recovery housing. Assessments were conducted at 1, 3
      and 6 months after treatment enrollment. SETTING: Out-patient drug-free substance
      abuse treatment program in Baltimore, Maryland. PARTICIPANTS: Patients (n = 243)
      who completed medication-assisted opioid detoxification. MEASUREMENTS: Primary
      outcome was drug abstinence (opioid- and cocaine-negative urine and no self
      reported opioid or cocaine use in the previous 30 days). Secondary outcomes
      included abstinence at all time-points (1, 3 and 6 months), days in recovery
      housing and employment. FINDINGS: Overall rates of drug abstinence were 50% for
      RH + RBT, 37% for RH and 13% for UC (P < 0.001). At 6 months, RH + RBT
      participants remained more likely to meet abstinence criteria than UC
      participants (37% versus 20%, P = 0.016). Length of stay in recovery housing
      mediated abstinence outcomes and was longer in RH + RBT (49.5 days) than in RH
      (32.2 days; P < 0.002). CONCLUSIONS: Abstinence-contingent recovery housing
      improves abstinence in opioid-dependent adults following medication-assisted
      detoxification. The addition of intensive 'reinforcement-based treatment'
      behavioural counseling further improves treatment outcomes, in part by promoting
      longer recovery house stays.

PMID- 22151479
TI  - Introgression of mitochondrial DNA among Myodes voles: consequences for
      energetics?
AB  - BACKGROUND: Introgression of mitochondrial DNA (mtDNA) is among the most
      frequently described cases of reticulate evolution. The tendency of mtDNA to
      cross interspecific barriers is somewhat counter-intuitive considering the key
      function of enzymes that it encodes in the oxidative-phosphorylation process,
      which could give rise to hybrid dysfunction. How mtDNA reticulation affects the
      evolution of metabolic functions is, however, uncertain. Here we investigated how
      morpho-physiological traits vary in natural populations of a common rodent (the
      bank vole, Myodes glareolus) and whether this variation could be associated with
      mtDNA introgression. First, we confirmed that M. glareolus harbour mtDNA
      introgressed from M. rutilus by analyzing mtDNA (cytochrome b, 954 bp) and
      nuclear DNA (four markers; 2333 bp in total) sequence variation and
      reconstructing loci phylogenies among six natural populations in Finland. We then
      studied geographic variation in body size and basal metabolic rate (BMR) among
      the populations of M. glareolus and tested its relationship with mtDNA type.
      RESULTS: Myodes glareolus and its arctic neighbour, M. rutilus, are reciprocally
      monophyletic at the analyzed nuclear DNA loci. In contrast, the two northernmost
      populations of M. glareolus have a fixed mitotype that is shared with M. rutilus,
      likely due to introgressive hybridization. The analyses of phenotypic traits
      revealed that the body mass and whole-body, but not mass corrected, BMR are
      significantly reduced in M. glareolus females from northern Finland that also
      have the introgressed mitotype. Restricting the analysis to the single population
      where the mitotypes coexist, the association of mtDNA type with whole-body BMR
      remained but those with mass corrected BMR and body mass did not. Mitochondrial
      sequence variation in the introgressed haplotypes is compatible with demographic
      growth of the populations, but may also be a result of positive selection.
      CONCLUSION: Our results show that the phenotypic traits vary markedly along the
      north-south axis of populations of M. glareolus. This variation may be related to
      adaptation to local environments and coincides with the gradient of genome
      reticulation between M. glareolus and M. rutilus, which was assessed by mtDNA
      introgression. Introgression of mtDNA may have affected morpho-physiological
      traits but do not show strong effects on either body mass or basal metabolic rate
      alone. We discuss the causes and biological meaning of our results and the means
      to clarify these questions in future research.

PMID- 22151480
TI  - Adult-onset angiocentric glioma of epithelioid cell-predominant type of the
      mesial temporal lobe suggestive of a rare but distinct clinicopathological subset
      within a spectrum of angiocentric cortical ependymal tumors.
AB  - Angiocentric glioma (AG) is defined as an epilepsy-associated stable or slowly
      growing cerebral tumor primarily affecting children and young adults,
      histologically consisting mainly of monomorphic, bipolar spindle-shaped cells and
      occasional round to monopolar columnar epithelioid cells, showing angiocentric
      growth pattern and features of ependymal differentiation. We describe two
      clinicopathologically unusual cases of AG. Case 1 is a 54-year-old woman with a
      10-year history of complex partial seizures. MRI revealed non-enhancing T1-low,
      T2/fluid-attenuated inversion recovery (FLAIR)-high intensity signal change in
      the left hippocampus and amygdala. After selective amygdalohippocampectomy, she
      had rare non-disabling seizures on medication for over 50 months (Engel's class
      I). Case 2 is a 37-year-old man with a 3-year history of complex partial
      seizures. MRI revealed non-enhancing T1-low, T2/FLAIR-high intensity signal
      change in the left uncus and amygdala. After combined amygdalohippocampectomy and
      anterior temporal lobectomy, he has been seizure-free for over 11 months.
      Histologically the tumors in both cases consisted mainly of infiltrating
      epithelioid cells (GFAP- ~+/-, S-100-) with perinuclear epithelial membrane
      antigen (EMA)-positive dots and rings, showing conspicuous single- and multi
      layered angiocentric arrangements. Occasional tumor cells showed spindle-shaped
      morphology (GFAP+, S-100+) with rare EMA-positive dots aligned radially and
      longitudinally along parenchymal blood vessels. Focal solid areas showed a
      Schwannoma-like fascicular arrangement with rare EMA-positive dots and/or sheets
      of epithelioid cells with abundant EMA dots. Electron microscopic investigation
      demonstrated features of ependymal differentiation. These cases, together with a
      few similar cases previously reported, appear to represent a rare but distinct
      clinicopathological subset of AG characterized by adult-onset, mesial temporal
      lobe localization and epithelioid cell-predominant histology.

PMID- 22151481
TI  - A comparative study to evaluate the effect of two different abutment designs on
      soft tissue healing and stability of mucosal margins.
AB  - AIM: To evaluate the effect of two different abutment designs on soft tissue
      healing and the stability of the mucosal margin in vivo. MATERIALS AND METHODS:
      Twenty-nine subjects received two, non-adjacent endosseous implants in the
      esthetic zone. Subsequently, conventional (control) and curved abutments
      (experimental) were placed in combination with a temporary restoration (left
      right randomization). Plaster models of the healed sites were made to assess the
      stability of the soft tissues at baseline and after 6 weeks. To measure deseating
      force, a dontrix gauge was used while removing the abutments after 6 weeks.
      RESULTS: Although visually, differences in the transmucosal area were observed,
      the differences in marginal recession and in deseating force between abutments
      from the experimental and the control group never reached a statistically
      significant level. In general, some gain in soft tissue height was seen in both
      groups. Angled abutments elicited recession at all buccal sites (P = 0.003-0.02).
      CONCLUSION: Abutments with a circumferential groove do not lead to a different
      response of the mucosal margin compared with a regular abutment, and are no more
      resistant upon removal than regular abutments after 6 weeks of function.

PMID- 22151482
TI  - The right place at the right time.

PMID- 22151483
TI  - A consensus statement regarding the present suggested titration for prialt
      (ziconotide).

PMID- 22151484
TI  - The costs and benefits of deep brain stimulation surgery for patients with
      dystonia: an initial exploration.
AB  - Objectives.  To perform a preliminary cost-utility and cost-benefit of deep brain
      stimulation (DBS) in the treatment of dystonia, Materials and Methods.  We
      conducted a prospective study of 26 patients undergoing DBS for the treatment of
      dystonia. We performed a cost-utility analysis using the Euroquol (EQ-5D)
      questionnaire. A cost-benefit analysis used the willingness-to-pay principle and
      costs of treatment were calculated retrospectively in order to calculate the cost
      benefit. Results.  We found that the EQ-5D score improved from 29 to 76.2 points
      after surgery, an incremental utility of 0.47. There was an overall gain of 0.94
      quality-adjusted life-years (QALY) with a cost of L33,980 per QALY. Conclusions. 
      DBS for dystonia, while an expensive treatment, compares favorably to therapies
      that are commonly used for other conditions.

PMID- 22151485
TI  - The Utility of a 7-Day Percutaneous Spinal Cord Stimulator Trial Measured by a
      Pain Diary: A Long-term Retrospective Analysis.
AB  - Objective.  The purpose of this study was to investigate the utility of a 7-day
      percutaneous spinal cord stimulator trial using a 7-day diary to measure outcomes
      during the trial and at long-term follow-up. Materials and Method.  Diaries
      completed prior to and during the trial were analyzed, as was a follow-up
      questionnaire. Trial and follow-up data were compared using nonparametric
      statistics and descriptive analyses. Result.  Results revealed statistically
      significant differences between pretrial and long-term follow-up measures of
      pain, mood, anxiety, and suffering for patients with positive trials. Expected
      differences existed between patients with positive and negative trials during the
      trial. Responders to permanent implantation differed on anxiety before and after
      the trial compared to nonresponders. Conclusion.  Patients who underwent a 7-day
      percutaneous trial, had a positive trial and received permanent implantation
      fared well long-term. The 7-day diary did not result in a superior method of
      determining responders vs. nonresponders at long-term follow-up. More research is
      needed to determine whether different quantitative measures would predict long
      term outcome.

PMID- 22151486
TI  - The Use of Continuous Intrathecal Infusion of Octreotide in Patients with Chronic
      Pain of Noncancer Origin: An Evaluation of Side-effects and Toxicity in a
      Prospective Double-blind Fashion.
AB  - Introduction.  Intrathecal octreotide has been considered an alternative to
      opioids in chronic infusion for pain. Octreotide is an analog of the growth
      hormone sandostatin. Previous work has shown the drug to be efficacious in cancer
      patients who had failed intrathecal opioids. In this study, we examined the
      safety of intrathecal octreotide in noncancer pain using continuous intrathecal
      infusion. Methods.  We examined 20 patients in a double-blind, prospective,
      randomized fashion comparing safety and adverse effects using saline or
      octreotide. Data collected include neurologic examination, adverse effect
      reporting, and cognitive testing. The study was reviewed and approved by the
      Saint Francis Hospital Institutional Review Board, which also conducted and
      approved the authorization to use and disclose protected health information for
      research purposes which describes the privacy law, Health Insurance Portability
      and Accountability Act (HIPAA). The Saint Francis Hospital IRB and FDA approved
      the ongoing use of intrathecal octreotide for research. Conclusions.  Intrathecal
      octreotide, at doses as high as 20 ug/hr, appeared to be as safe as saline when
      given as a continuous intrathecal infusion. Further work is needed on dose-range
      analysis and efficacy.

PMID- 22151487
TI  - Lower urinary tract and bowel disorders and multiple sclerosis: role of sacral
      neuromodulation: a preliminary report.
AB  - Objective.  In the present study we wanted to determine whether sacral
      neuromodulation benefits patients with bladder and bowel symptoms caused by
      multiple sclerosis (MS). Methods.  At our Institute, five patients with MS
      underwent unilateral implantation of a sacral neuromodulation system, InterStim
      (Medtronic Inc., Minneapolis, Minnesota, USA), between April 2001 and June 2002;
      the mean follow-up was 30.4 months (range 24-38). The following parameters were
      evaluated before and after implant of the neurostimulator device: number of daily
      voidings, number of incontinent episodes, residual urine, Wexner score, quality
      of life (QoL), and psychological impact. Results.  There was an overall 81.4%
      decrease of urgency and frequency with a significant decrease in the number of
      upper urinary tract infections and fever; there was a slight improvement in bowel
      function; there was an overall 51.8% improvement in the QoL and a discernible
      improvement emotional well-being. Conclusions.  Unilateral chronic sacral
      neuromodulation can be a valuable treatment for neurogenic bladder and bowel
      disorders associated with MS.

PMID- 22151488
TI  - Tined lead implantation: results of the first 37 implants in maastricht.

PMID- 22151489
TI  - Ten years' experience in neuromodulation in maastricht.

PMID- 22151490
TI  - Sacral nerve stimulation for fecal incontinence: current worldwide results.

PMID- 22151492
TI  - Pathophysiology, measurement, and treatment of spasticity in children.

PMID- 22151491
TI  - Sacral nerve stimulation for pelvic floor and bladder dysfunction in adults and
      children.

PMID- 22151493
TI  - Variability in gait analysis data in spastic children.

PMID- 22151494
TI  - Percutaneous radiofrequency treatment adjacent to the dorsal root ganglion as a
      treatment modality for spasticity in children.

PMID- 22151495
TI  - Additional effect of botulinum toxin a treatment on upper limb functional skills
      in children with hemiparetic cerebral palsy.

PMID- 22151496
TI  - A pilot study to investigate the effects of electrical stimulation on recovery of
      hand function and sensation in subacute stroke patients.
AB  - Objectives.  1) To compare the effect of cyclic neuromuscular electrical
      stimulation (NMES) of the forearm and elbow extensor muscles with passive
      stretching exercises on hand function and sensation following stroke. 2) To
      inform sample size for a larger randomized controlled trial (RCT). Materials and
      Methods.  Twenty-two subjects with hemiplegia resulting from a stroke during the
      previous 12 months were randomly allocated into stimulation (treatment) and
      exercise (control) groups. Stimulation was applied to the elbow, and forearm
      extensor muscle groups of the hemiplegic arm for 12 weeks. Subjects in the
      control group were taught passive stretching exercises for the same period. The
      primary outcome measure was the Action Research Arm test (ARAT). Sensation was
      tested using two-point discrimination. Statistical analysis applied nonparametric
      analysis of covariance (ancova). Results.  Statistically significant between
      group differences in change in ARAT scores were shown between the two groups
      after 12 weeks of treatment (p = 0.003) and following 12 further weeks without
      intervention (p = 0.012). There were no significant differences in sensation.
      Conclusions.  1) A significant treatment effect of electrical stimulation over
      passive exercise has been demonstrated in a group of 22 subacute stroke patients,
      randomized into two equal groups and further work identified which may help to
      improve recovery of hand function and sensation following stroke. 2) A sample
      size of 24 subjects in each group has been estimated assuming a two-sided test
      significance level of 5% with 80% power, primary outcome variability SD = 6.75, a
      minimum difference of ten ARAT score units, and a 10% dropout rate.

PMID- 22151497
TI  - A preliminary feasibility study of different implantable pulse generators
      technologies for diaphragm pacing system.
AB  - Diaphragm pacing stimulation (DPS) for ventilator-dependent patients provides
      several advantages over conventional techniques such as phrenic nerve pacing or
      mechanical ventilator support. To date, the only existing system for DPS uses
      lead electrodes, percutaneously attached to an external pulse generator (PG).
      However, for a widespread use of this technique it would be more appropriate to
      eliminate the need for percutaneous wire and use a totally implantable system.
      The aim of this study was to determine if it were feasible to replace the
      external PG by an implantable system. We present here the results of a
      preliminary study of two different PG, currently used in other electrical
      stimulation (ES) clinical applications, which could be used as implantable DPS
      systems. One radio-frequency-powered PG, one rechargeable battery-powered PG, and
      the current external PG were tested. Each was attached to the externalized part
      of the wires, connected to the diaphragm and tidal volume (TV) was measured in
      one ventilator-dependent patient who has been using the current percutaneous
      stimulator for 3 years. Results indicated that both implantable PGs could achieve
      equivalent ventilatory requirements to the current external stimulator. No
      significant differences were observed between the three PG systems when
      stimulating the electrodes as used in the patient's own chronically attached PG
      system. We found that TV increased with increases in charge and frequency as
      expected when stimulating the patient's electrodes individually and in
      combination with each PG system. These results are a significant step toward
      developing a totally implantable DPS system for the ventilator-dependant
      patients. Further clinical tests to demonstrate the safety and efficacy of a
      fully implanted DPS system are warranted.

PMID- 22151498
TI  - Characterization and localization of prodiginines from Streptomyces lividans
      suppressing Verticillium dahliae in the absence or presence of Arabidopsis
      thaliana.
AB  - The ascomycete Verticillium dahliae causes worldwide vascular wilt of many field
      and horticultural plants. The melanized resting structures of this fungus, so
      called microsclerotia, survive for many years in soils and continuously re-infect
      plants. Due to the absence of known fungicides, Verticillium wilt causes immense
      crop losses. We discovered that the Gram-positive, spore-forming soil bacterium
      Streptomyces lividans expresses members of the prodiginine family during co
      cultivation with V. dahliae. Using HPLC and LC-MS analysis of cultures containing
      S. lividans alone or grown together with V. dahliae, we found that
      undecylprodigiosin [394.4 M+H](+) is highly abundant, and streptorubin B [392.4
      M+H](+) is present in smaller amounts. Within co-cultures, the quantity of
      undecylprodigiosin increased considerably and pigment concentrated at and within
      fungal hyphae. The addition of purified undecylprodigiosin to growing V. dahliae
      hyphae strongly reduced microsclerotia formation. Undecylprodigiosin was also
      produced when S. lividans grew on the roots of developing Arabidopsis thaliana
      plants. Furthermore, the presence of the undecylprodigiosin producer led to an
      efficient reduction of V. dahliae hyphae and microsclerotia on plant-roots. Based
      on these novel findings and previous knowledge, we deduce that the prodiginine
      investigated leads to multiple cellular effects, which ultimately impair specific
      pathways for signal transduction and apoptosis of the fungal plant pathogen.

PMID- 22151499
TI  - The relationship between osteoporosis and periodontitis in women aged 45-70
      years.
AB  - OBJECTIVE: To explore the possible relationship between the osteoporotic
      condition and the severity of periodontitis in women aged 45-70 years. MATERIALS
      AND METHODS: Ninety women with generalized chronic periodontitis, aged 45-70
      years, were studied. Areal bone mineral density (BMDa) was assessed using
      standardized dual energy X-ray absorptiometry (normal: T-score >= -1, osteopenic:
      -2.5 <= T-score <-1, osteoporotic: T-score < -2.5). Gingival index (GI), bleeding
      on probing, clinical attachment loss (CAL), probing pocket depth and gingival
      recession (GR) were recorded. Periodontitis severity was represented by CAL.
      Menopausal condition and smoking were documented. RESULTS: Mean GI, bleeding on
      probing, CAL and GR were significantly greater for osteoporotic women than women
      with normal BMDa (P = 0.002, P = 0.01, P = 0.04, respectively). Osteopenic women
      and women with normal BMDa significantly differed in mean GI (P = 0.02). The
      associations found between osteoporotic women and women with normal BMDa and the
      associations found between osteopenic women and women with normal BMDa existed
      even after adjusting for smoking and menopausal status. CONCLUSION: Subjects with
      osteoporosis (OPR) presented with greater CAL than the subjects with normal BMDa,
      which suggests a greater severity of periodontitis. Subjects with OPR had greater
      GR than the subjects with normal BMDa. Subjects with osteopenia and subjects with
      normal BMDa did not differ in CAL, which might suggest that the early diagnosis
      of reduced BMDa, prior to the establishment of a significant negative impact on
      the periodontal tissues, might be important. Smoking and menopausal status did
      not alter these associations.

PMID- 22151500
TI  - Examining the breastfeeding support resources of the public health nursing
      services in Ireland.
AB  - AIMS AND OBJECTIVES: The aim of the study was to review breastfeeding support
      provided by Public Health Nurses in Ireland. The objectives were to identify the
      availability of appropriate guiding policies, educational preparation, attitude
      of Public Health Nurses and the availability and use of other supportive
      services. BACKGROUND: Breastfeeding rates in Ireland are among the lowest in
      Europe. The main source of formal support for breastfeeding mothers in the
      community in Ireland is from Public Health Nurses who can make referral to other
      non-statutory resources. The nature of this support is determined by policies
      guiding clinical practice and education that increases breastfeeding confidence
      and competence of all personnel. Consequently, an assessment of breastfeeding
      resources requires an analysis of all these variables. DESIGN: A large
      quantitative, cross-sectional study was conducted, involving Public Health Nurses
      and mothers. This paper represents the results from the perspective of Public
      Health Nurses. METHOD: Directors of Public Health Nursing (n = 24) and Public
      Health Nurses (n = 204) completed self-report questionnaires by mail and online.
      Data were analysed using the Statistical Package for Social Sciences and reported
      using descriptive and inferential statistics. RESULTS: Public Health Nurses are
      well educated to support breastfeeding and have a positive attitude and a high
      degree of self-assessed confidence and competence. A wide variety of non
      statutory support exists for breastfeeding but is not always used to their full
      potential. CONCLUSION: Standardising educational requirements for Public Health
      Nurses in supporting breastfeeding is an area that requires attention.
      Ultimately, service delivery in relation to supporting breastfeeding mothers
      would benefit from being more timely and responsive. RELEVANCE TO CLINICAL
      PRACTICE: Awareness of support resources is necessary for Public Health Nurses to
      make appropriate referrals for breastfeeding mothers. Furthermore, Directors of
      Public Health Nursing need to encourage the breastfeeding supportive role of
      Public Health Nurses and facilitate continuing professional development.

PMID- 22151501
TI  - Guidelines in neuromodulation: education in the era of evidence (ignorance?)
      based medicine.

PMID- 22151502
TI  - Neurotech report.

PMID- 22151503
TI  - Damaged insulation mimicked symptoms of occipital stimulator lead migration.
AB  - INTRODUCTION: The use of occipital nerve stimulators for the treatment of
      migraines has recently been suggested. However, there have been reports of
      complications, including lead migration causing local muscle stimulation and
      spasm with local burning sensation and loss of successful neuromodulation. CASE:
      We report a case of a patient who had successful permanent implantation and then
      presented with suspicion of lead migration. Upon examination of the lead at time
      of repositioning it was found that the insulation had eroded and the conducting
      wires exposed at the anchor site. DISCUSSION: Disruption of occipital nerve
      stimulator lead insulation may mimic lead migration with failure of
      neuromodulation, spasm, and local burning sensations. Prior to reimplanting, a
      lead should be thoroughly inspected to ensure there is no mechanical failure.
      Anchoring should be performed with gentle direct suturing or the use of a
      protective anchoring device.

PMID- 22151504
TI  - Targeting and fielding: not the same!

PMID- 22151508
TI  - Medication abortions among New York City residents, 2001-2008.
AB  - CONTEXT: Population-level research on trends in medication abortions and the
      association of patient characteristics and facility type with procedure choice is
      limited. Surveillance is necessary to ensure accurate reporting and understanding
      of service availability. METHODS: New York City induced abortion data for 2001
      2008 were used to calculate medication abortion prevalence among women undergoing
      early abortions (i.e., at nine or fewer weeks of gestation). Multiple logistic
      regression analysis was used to assess associations between selected
      characteristics and having a medication, as opposed to surgical, abortion.
      Proportions of patients who went to clinics or hospitals that did not offer
      medication abortions were also calculated. RESULTS: Five percent of early
      abortions were medication procedures in 2001; the proportion rose to 13% by 2008.
      Eighty-two percent of medication abortions in 2008 were performed at freestanding
      clinics, and 10% at doctors' offices. The likelihood of having had a medication
      abortion, rather than a surgical one, was lower among blacks and Hispanics than
      among whites (odds ratios, 0.5 and 0.7, respectively). Medication abortions were
      more likely among women with more than 12 years of education than among those
      with less than a high school education (2.1), and more likely among those who
      went to doctors' offices than among clinic patients (3.6). Throughout 2001-2008,
      medication abortions were not available at 50% of hospitals and 31% of clinics
      that provided early abortions. CONCLUSIONS: The increasing prevalence of
      medication abortions highlights the importance of active surveillance. Because
      many facilities do not offer the procedure, a better understanding of barriers to
      provision is needed.

PMID- 22151509
TI  - A study of physician recommendations for reversible contraceptive methods using
      standardized patients.
AB  - CONTEXT: Health care providers may influence patients' choice of contraceptive
      method, yet little is known about the recommendations they make to their
      patients. METHODS: In 2007-2008, a total of 468 physicians at four family
      medicine and obstetrics and gynecology meetings were randomly assigned to view
      one of 18 videos of a patient seeking contraceptive advice; the patients were
      standardized for most relevant behaviors and characteristics, but differed by
      race and ethnicity, socioeconomic status and gynecologic history. Participants
      provided their demographic and practice characteristics and completed a survey
      about their contraceptive recommendations for the patient. Multivariate logistic
      regression analyses were conducted to identify associations between physician
      characteristics and recommendations for specific contraceptive methods. RESULTS:
      The most frequently recommended methods were the pill (89%) and ring (80%),
      followed by the levonor-gestrel IUD (64%), patch (56%), injectable (49%) and
      copper IUD (45%). Oral contraceptives were more likely to be recommended by
      private practice physicians than by academic physicians (odds ratio, 2.9).
      Recommendations for the ring were less common among family physicians and those
      56 or older than among obstetrician-gynecologists and those 35 or younger (0.6
      and 0.3, respectively), and more common among physicians in private practice than
      among those in academia (2.4). The patch and injectable were more commonly
      recommended by family physicians than by obstetrician-gynecologists (2.6 and 2.5,
      respectively). Both IUD types were recommended less often by physicians 36 or
      older than by younger ones (0.2-0.5). DISCUSSION: The advice women receive about
      contraception may vary according to the characteristics of their provider.
      Research on the reasons for these differences is needed.

PMID- 22151510
TI  - Adolescent mothers' postpartum contraceptive use: a qualitative study.
AB  - CONTEXT: Effective contraceptive use among first-time adolescent mothers can
      reduce the risk of a rapid repeat pregnancy and associated negative maternal and
      child health outcomes. Many adolescent mothers begin using a highly effective
      method after delivery; however, their rates of contraceptive discontinuation are
      high. Little research has explored the factors that influence adolescents'
      postpartum contraceptive use. METHODS: In-depth interviews were conducted with 21
      black, white and Latina adolescent first-time mothers from rural and urban areas
      of North Carolina between November 2007 and February 2009. In addition,
      interviews were conducted with 18 key informants-professionals who work closely
      with adolescent mothers. Interviews explored adolescent mothers' health
      behaviors, including contraceptive use, before and after pregnancy. Content
      analysis was used to identify key themes and patterns. RESULTS: Teenagers' use of
      contraceptives, particularly injectables, IUDs and implants, increased
      postpartum. Reasons for this improvement included improved clarity of intention
      to avoid pregnancy and improved contraceptive knowledge, support and access after
      delivery. However, this increased access often did not continue long after
      delivery, and levels of method switching were high. Among the barriers to
      postpartum contraceptive use that key informants cited were lack of information
      and parental support, as well as the loss of Medicaid and continuity of care.
      CONCLUSIONS: Ongoing follow-up may help reduce adolescent mothers' risk of
      contraceptive discontinuation postpartum. Increasing use of long-acting methods
      also may help reduce their vulnerability to gaps in contraceptive use and
      discontinuation, which increase the risk of unintended pregnancy.

PMID- 22151511
TI  - STD and HIV testing behaviors among black and Puerto Rican young adults.
AB  - CONTEXT: Given the high rates of infection among urban young adults, STD and HIV
      testing promotion is a public health priority. To inform future testing efforts,
      lifetime and recent testing behaviors of this population within casual and
      serious relationships should be better understood. METHODS: Data from a 2007-2008
      study conducted in select neighborhoods in Hartford and Philadelphia were used to
      examine self-reported STD and HIV testing behaviors and attitudes among 483
      sexually active black and Puerto Rican young adults aged 18-25. Multivariate
      ordered logit regression analyses were conducted to assess characteristics
      associated with lifetime number of STD tests. RESULTS: More than eight in 10
      participants reported having been tested for STDs, and a similar proportion for
      HIV, most of them multiple times. Nineteen percent had ever had an STD diagnosis.
      A majority-86%-perceived their risk of STD infection in the next year as "not at
      all likely." Sixty-one percent of those in serious relationships reported that
      both partners had been tested, compared with 25% of those in casual
      relationships. Characteristics associated with higher lifetime number of STD
      tests were being female (odds ratio, 2.2), being from Philadelphia (2.5), being
      black (1.5), having lived with two or more serious partners (1.7) and having ever
      received an STD diagnosis (2.3). DISCUSSION: Despite their risks, participants
      did not perceive themselves to be at risk of STDs. However, they did report
      testing repeatedly. Testing was highly acceptable, particularly within serious
      relationships. Questions about the timing of testing initiation and repeat
      testing merit attention for the benefits of widespread testing to be fully
      realized.

PMID- 22151512
TI  - A comparative study of interventions for delaying the initiation of sexual
      intercourse among Latino and black youth.
AB  - CONTEXT: Latino and black adolescents are disproportionately affected by STDs,
      including HIV, and unintended pregnancies. Few parent-based interventions have
      targeted these youth, focused on early adolescence and had high participation
      rates. METHODS: Between 2003 and 2009, a randomized clinical trial was conducted
      with 2,016 Latino and black mother-adolescent dyads in New York City. Adolescents
      were eligible if they were in grade 6 or 7. Dyads were assigned to one of three
      conditions: a parent-based intervention, Families Talking Together (FTT); an
      adolescent-only intervention, Making a Difference! (MAD); or a combined FTT+MAD
      intervention. Respondents completed questionnaires at baseline and 12 months
      later. Single-degree-of-freedom contrasts and logistic regression analysis were
      used to evaluate differences in outcomes by intervention. RESULTS: The proportion
      of youth who reported ever having engaged in vaginal intercourse increased over
      the study period by eight percentage points among those in the MAD group, five
      points in the FTT group and three points in the combined group; the differences
      among these increases were not statistically significant. Adolescents in the two
      FTT groups were significantly more likely than those in the MAD group to indicate
      that their mother had talked to them about not having intercourse (79% vs. 68%).
      They also scored higher than youth in the MAD group on measures of communication
      and perceived maternal attributes, and lower on activities that might lead to
      risky behaviors. CONCLUSIONS: The proportions of adolescents who initiated
      intercourse during the study period were not significantly different across
      groups, implying that the interventions were comparable. Findings suggest that
      FTT may have led to improved parenting behaviors.

PMID- 22151513
TI  - Characteristics related to effective contraceptive use among a sample of nonurban
      Latinos.
AB  - CONTEXT: A better understanding of effective contraceptive use among Latinos is
      needed to reduce their high rate of unintended pregnancy. Most research has
      focused on urban Latinas and has overlooked the relationship context of effective
      contraceptive use. METHODS: Interviews were conducted among a sample of 450
      Latino women and men aged 18-25 in sexual relationships, who were recruited from
      community sites in four rural Oregon counties in 2006. Bivariate and multinomial
      logistic regression analyses were used to examine the associations between
      effective contraceptive use and -individual, cultural and relationship
      characteristics. RESULTS: Half of participants reported effective contraceptive
      use in their primary relationships: Thirty-six percent consistently used a female
      method, and 15% consistently used condoms. Acculturation and confidence in one's 
      ability to practice contraception with a primary partner were associated with
      female method use rather than no effective use (risk ratios, 0.7 and 1.7,
      respectively). Participation in sexual decision making was positively associated
      with condom use rather than no effective method use (2.2) or female method use
      (1.9); partner involvement in birth control was positively associated with condom
      use rather than female method use (1.8). CONCLUSIONS: Variations in effective
      contraceptive use among nonurban Latinos appear related to relationship
      characteristics and dynamics. Contraceptive counseling and unintended pregnancy
      prevention programs that are tailored to reflect relationship contexts and to
      include male partners where appropriate could improve the quality and cultural
      relevance of services among nonurban Latinos.

PMID- 22151521
TI  - Identification of immune cells by flow cytometry in vaginal lavages from women
      with vulvovaginitis and normal microflora.
AB  - PROBLEM:   The extent of the vaginal immune response is not fully determined. The
      purpose of this study was to evaluate the vaginal immune cells from women with
      vulvovaginitis (VV). METHOD OF STUDY: A total of 142 volunteers diagnosed with
      bacterial vaginosis (BV), vulvovaginal candidiasis (VC), and BV associated with
      VC or normal microflora were sampled to evaluate the immune cells by flow
      cytometry. The immune cells were obtained by vaginal lavage and labeled with
      fluorochrome-conjugated monoclonal antibodies to identify neutrophil
      granulocytes, macrophages, CD4(+) and CD8(+) T lymphocytes, B lymphocytes, and NK
      lymphocytes. RESULTS: Neutrophil granulocytes were present in 84.6% of samples
      among the leukocyte populations. Considering samples in which neutrophils were
      present, the mean percentage of neutrophil granulocytes was significantly higher
      in women with VC than BV and normal microflora and was significantly lower in
      women with BV than normal microflora. Macrophages and lymphocytes were present in
      a lower percentage of samples. The mean percentage of CD4(+) T lymphocytes in
      vaginal lavages was significantly higher in VC and BV compared with women with
      normal microflora. CONCLUSIONS: Neutrophils were the predominant leukocytes and
      were associated with VC and inversely with BV. CD4(+) T lymphocytes were
      associated with both VC and BV.

PMID- 22151522
TI  - Safety and efficacy of intrathecal baclofen infusion by implantable pump for the
      treatment of severe spinal spasticity: a spanish multicenter study.
AB  - Objective. To assess long-term efficacy, safety and functional benefit of
      intrathecal baclofen for severe spinal spasticity. Materials and Methods. This
      prospective multicenter study was performed in two stages: the first one
      consisted of an intrathecal bolus injection of baclofen, and the second of a
      continuous intrathecal baclofen infusion by means of an implantable pump. The
      sample consisted of 72 adult patients with severe spinal spasticity. Sixty-four
      were implanted and followed for 36 months. Muscular tone, spasms, and functional
      scales were evaluated before and periodically after administration of the drug,
      with a follow-up period of 36 months. Results. A very significant decrease in
      tone and spasms was observed in all cases (p < 0.001). Tolerance appeared during
      the first 12 months, increasing doses from a mean initial dose of 83.2 MUg (range
      25-200 MUg) to a mean final dose of 270 MUg (range 25-800 MUg). Later on,
      efficacy remained stable, except in cases of mechanical problems of the infusion
      system.

PMID- 22151523
TI  - Psychological variables predict decisions regarding implantation of a spinal cord
      stimulator.
AB  - Objectives. To examine the psychological status of candidates for spinal cord
      stimulator implantation and elucidate possible personality variables that impact
      implantation decisions. Materials and Methods. This study surveyed 47
      consecutively referred patients for possible implantation in an academic medical
      center outpatient pain clinic. Participants completed the Minnesota Multiphasic
      Personality Inventory-2 (MMPI-2), McGill Pain Questionnaire, and a locus of
      control scale. MANOVA and discriminant analysis was utilized to examine
      personality variables and implantation decisions. Results. Individuals who
      ultimately declined implantation of the stimulator were psychologically different
      from those acceding to permanent implantation. Permanently implanted patients
      were more open to admitting psychological distress, less somatically preoccupied,
      and possibly more submissive than those who refused. Conclusions. The MMPI-2 was
      able to predict final implantation status. The results suggest that patient
      personality characteristics exercise a significant role in decisions regarding
      stimulator implantation.

PMID- 22151524
TI  - Application of a psychological decision algorithm for the selection of patients
      susceptible to implantation of neuromodulation systems for the treatment of
      chronic pain. A proposal.
AB  - Objective. The application of a decision algorithm is described here for the
      inclusion of patients in a protocol of therapeutic intervention by the use of an
      implantable neuromodulation system. This algorithm is based on the assessment of
      the psychological profiles of the patients and their environment. Materials and
      methods. This algorithm was applied to patients in the Multidisciplinary Unit for
      Pain Treatment at the General University Hospital of Valencia (Spain) by means of
      a clinical interview performed by the Psychology Department prior to the
      therapeutic decision. It was applied to two samples. The first sample was made up
      of patients psychologically assessed prior to implantation; the second sample was
      made up of implanted patients to whom the algorithm was applied retrospectively,
      by reviewing their clinical medical history. Results. In the first sample, pain
      relief of 50% or higher was obtained by 80% of the subjects studied, while in the
      second the percentage decreased to 63%. While the rate of implants removed in
      sample 1 was 4.2%, the rate of implants removed in sample 2 was 7.5% due to lack
      of efficacy. In a third sample, made up of implanted patients from sample 1 and
      sample 2, a discriminant analysis was performed using a pooled variable.
      Conclusion. The results of the application of the pooled analysis confirm the
      need for considering the psychological profile as a variable predicting an
      optimum result in the therapeutic treatment of chronic pain.

PMID- 22151525
TI  - Selective Nerve Root Stimulation (SNRS) in the Treatment of End-Stage, Diabetic,
      Peripheral Neuropathy: A Case Report.
AB  - Spinal cord stimulation (SCS) for the treatment of painful peripheral neuropathy
      (PN) has been met with mixed results. It has been suggested that early-stage
      symptoms that are sympathetically maintained (SMP) are more likely to respond to
      SCS, while progressive sympathetically independent symptoms (SIP) will not.
      Peripheral nerve stimulation (PNS), however, has successfully treated certain SIP
      presentations. With the advent of new selective nerve root stimulation (SNRS)
      strategies, the possibility of utilizing epidural, peripheral neurostimulation
      was investigated in a patient with endstage, diabetic, "dying back" peripheral
      SIP.

PMID- 22151526
TI  - Letter to the editor.

PMID- 22151527
TI  - Trends in the hospitalization of ischemic stroke in the United States, 1998-2007.
AB  - BACKGROUND: The late 1990s/early 2000s was a time of change in both the
      prevention and acute care of ischemic stroke, with primary prevention driven by
      increased utilization of antihypertensive, antiplatelet, anticoagulation, and
      lipid-lowering agents. AIM: To examine whether ischemic stroke hospitalization
      rates and outcomes in the United States have changed. METHOD: We retrospectively
      identified 894 169 hospitalizations with a primary diagnosis of ischemic stroke
      from 1 January 1998 through to 31 December 2007 in the Nationwide Inpatient
      Sample, the largest all-payer healthcare database in the United States. Annual,
      national case estimates were combined with US Census data to derive age-adjusted
      and age-specific population hospitalization rates. Temporal trends were tested
      using linear regression. RESULTS: From 1998 through 2007, there were an estimated
      4 382 336 ischemic stroke hospitalizations in the United States. Overall, the age
      adjusted rate of ischemic stroke hospitalization decreased from 184 to 128 per
      100 000 (P < 0.0001). Age-specific rates decreased among those 55+ years old (P <
      0.0001), but increased among those 25-34 and 35-44 years old (P < 0.001 and P <
      0.0001, respectively). Rates among those <25 and 45-54 years old were unchanged.
      In-hospital mortality decreased from 7.0% (standard error 0.1) to 5.4% (standard
      error 0.1) (P < 0.0001). Case proportion at the highest quintile of hospitals by
      annual caseload increased from 54.0% (standard error 2.1) to 61.8% (standard
      error 2.0) (P < 0.0001). Mean adjusted hospitalization costs increased from $9273
      (standard deviation 199) to $10 524 (standard deviation 77) (P < 0.0001).
      CONCLUSION: In 1998 through to 2007, the overall rate of ischemic stroke
      hospitalization in the United States decreased. However, rates among young adults
      increased. In-hospital mortality rates decreased over the study period.

PMID- 22151528
TI  - Current status of alternative hemodialysis regimens: an introduction.

PMID- 22151529
TI  - Comparative survival literature in intensive hemodialysis: limitations and future
      directions.
AB  - Modality comparisons focusing on survival outcomes of nocturnal hemodialysis
      (NHD) or short daily hemodialysis (SDHD) versus other treatment paradigms of end
      stage renal disease (ESRD) are sparse. The existing literature consists of cohort
      studies that are small, retrospective, underpowered, and poorly controlled. The
      only randomized controlled trial that included mortality as part of a complex
      composite endpoint is unable to provide information on survival only. Even if
      concerns with internal validity of this literature are set aside, the
      generalizability of a few hundred NHD and SDHD patients is an important
      consideration as it remains uncertain whether or not the purported survival
      benefits of intensive hemodialysis readily translate into similar benefits for
      the global ESRD population. The most feasible and definitive study design to
      compare NHD or SDHD to other treatment modalities (and to each other) is a large,
      prospective, matched cohort study.

PMID- 22151530
TI  - A sharp study, but with blunted conclusions.

PMID- 22151531
TI  - Comments on a case report of a Tenckhoff catheter allergy.

PMID- 22151534
TI  - Cryopreservation of cat testicular tissues: effects of storage temperature,
      freezing protocols and cryoprotective agents.
AB  - Cryopreservation of testicular tissue has become a part of gamete preservation in
      wild animal post-mortem. Using domestic cats as a model for wild felids, this
      study aimed to (i) investigate the effect of temperature for testicular tissue
      storage on sperm quality; (ii) compare efficiency of freezing protocols; and
      (iii) evaluate properties of cryoprotective agents to protect testicular sperm
      quality. A pair of testes from each cat (n = 9) was cut into four pieces. Three
      randomly selected pieces were allocated to be (i) fresh controls; (ii) stored at
      4  degrees C for 24 h; and (iii) stored at room temperature (28  degrees C) for
      24 h. After storage, the testicular tissue from each group was cut into 10 small
      pieces. One piece was assigned to be a control while the others were assigned to
      three freezing protocols; -80  degrees C (n = 3), vitrification (n = 3) or two
      step freezing (kept above liquid nitrogen vapour for 10 min and submerged in
      liquid nitrogen) (n = 3). Each of three pieces was frozen using dimethyl
      sulphoxide (DMSO), ethylene glycol (EG) or DMSO combined with EG. Sperm membrane
      (SYBR-14/EthD-1) and DNA (acridine orange) integrity were evaluated before and
      after cryopreservation. The storage of testicular tissue at room temperature
      decreased the percentage of sperm with intact membrane in fresh tissue (59.5 +/-
      30.5 vs 87.9 +/- 7.0%, p < 0.05). DNA integrity was decreased after 24-h storage
      either at 4  degrees C or room temperature (p < 0.05). The two-step freezing
      resulted in a higher percentage of sperm with intact plasma membrane than the
      other techniques. Dimethyl sulphoxide, EG and DMSO combined with EG provided
      similar protection for the sperm membrane and DNA from cryodamages. In
      conclusion, storage of testicular tissue at 4  degrees C is necessary to maintain
      sperm membrane integrity during transportation of tissue for cryopreservation in
      the freezing laboratory. The results provide information for male gamete rescue
      in felid particularly when they die unexpectedly in the field where freezing
      facilities are not well equipped.

PMID- 22151535
TI  - Diabetes care for older patients in America.
AB  - BACKGROUND: Underuse of diabetes care was common for older patients. This study
      examined whether patient or physician practice characteristics predict the
      likelihood of diabetes care. METHODS: We studied the 2006 and 2007 National
      Ambulatory Medical Care Survey data for a nationally-representative sample of
      2912 visits by older patients with diabetes. We examined the patterns of diabetes
      care, including diagnostic testing (glucose, haemoglobinA1c, blood pressure and
      cholesterol) and patient counselling services (diet/nutrition, exercise).
      Multivariate analysis was performed to identify independent predictors of
      diabetes care, controlling for patient and physician practice characteristics.
      All analyses were adjusted for the complex survey design. RESULTS: Having a
      designated primary care physician and the availability of electronic medical
      record or on-site laboratory testing were associated with more effective diabetes
      care (p < 0.05). If physician compensation relied on the productivity, physicians
      were less likely to provide diabetes care services (odds ratio = 0.5). The
      patterns of patient counselling and diagnostic testing services were similar
      (odds ratio = 2.5 and 18.2 for men; odds ratio = 1.8 and 9.6 for women). Older
      patients with diabetes were substantially more likely to receive diagnostic
      testing services than patient counselling. CONCLUSION: A designated primary care
      physician is crucial for providing recommended diabetes care services for older
      patients. Strengthening structural capabilities of primary care practices and
      implementing patient-centred primary care initiatives in concert with health
      system reforms are necessary to deliver the co-ordinated diabetes care with
      maximised health outcomes.

PMID- 22151537
TI  - Abstracts of the XXIII Annual Meeting of the Italian Society of Geriatric
      Surgery. Lecce, Italy. December 2-4, 2010.

PMID- 22151536
TI  - Empirical comparison of cross-platform normalization methods for gene expression
      data.
AB  - BACKGROUND: Simultaneous measurement of gene expression on a genomic scale can be
      accomplished using microarray technology or by sequencing based methods.
      Researchers who perform high throughput gene expression assays often deposit
      their data in public databases, but heterogeneity of measurement platforms leads
      to challenges for the combination and comparison of data sets. Researchers
      wishing to perform cross platform normalization face two major obstacles. First,
      a choice must be made about which method or methods to employ. Nine are currently
      available, and no rigorous comparison exists. Second, software for the selected
      method must be obtained and incorporated into a data analysis workflow. RESULTS:
      Using two publicly available cross-platform testing data sets, cross-platform
      normalization methods are compared based on inter-platform concordance and on the
      consistency of gene lists obtained with transformed data. Scatter and ROC-like
      plots are produced and new statistics based on those plots are introduced to
      measure the effectiveness of each method. Bootstrapping is employed to obtain
      distributions for those statistics. The consistency of platform effects across
      studies is explored theoretically and with respect to the testing data sets.
      CONCLUSIONS: Our comparisons indicate that four methods, DWD, EB, GQ, and XPN,
      are generally effective, while the remaining methods do not adequately correct
      for platform effects. Of the four successful methods, XPN generally shows the
      highest inter-platform concordance when treatment groups are equally sized, while
      DWD is most robust to differently sized treatment groups and consistently shows
      the smallest loss in gene detection. We provide an R package, CONOR, capable of
      performing the nine cross-platform normalization methods considered. The package
      can be downloaded at http://alborz.sdsu.edu/conor and is available from CRAN.

PMID- 22151538
TI  - Inter-plane artifact suppression in tomosynthesis using 3D CT image data.
AB  - BACKGROUND: Despite its superb lateral resolution, flat-panel-detector (FPD)
      based tomosynthesis suffers from low contrast and inter-plane artifacts caused by
      incomplete cancellation of the projection components stemming from outside the
      focal plane. The incomplete cancellation of the projection components, mostly due
      to the limited scan angle in the conventional tomosynthesis scan geometry, often
      makes the image contrast too low to differentiate the malignant tissues from the
      background tissues with confidence. METHODS: In this paper, we propose a new
      method to suppress the inter-plane artifacts in FPD-based tomosynthesis. If 3D
      whole volume CT images are available before the tomosynthesis scan, the CT image
      data can be incorporated into the tomosynthesis image reconstruction to suppress
      the inter-plane artifacts, hence, improving the image contrast. In the proposed
      technique, the projection components stemming from outside the region-of-interest
      (ROI) are subtracted from the measured tomosynthesis projection data to suppress
      the inter-plane artifacts. The projection components stemming from outside the
      ROI are calculated from the 3D whole volume CT images which usually have lower
      lateral resolution than the tomosynthesis images. The tomosynthesis images are
      reconstructed from the subtracted projection data which account for the x-ray
      attenuation through the ROI. After verifying the proposed method by simulation,
      we have performed both CT scan and tomosynthesis scan on a phantom and a
      sacrificed rat using a FPD-based micro-CT. RESULTS: We have measured contrast-to
      noise ratio (CNR) from the tomosynthesis images which is an indicator of the
      residual inter-plane artifacts on the focal-plane image. In both cases of the
      simulation and experimental imaging studies of the contrast evaluating phantom,
      CNRs have been significantly improved by the proposed method. In the rat imaging
      also, we have observed better visual contrast from the tomosynthesis images
      reconstructed by the proposed method. CONCLUSIONS: The proposed tomosynthesis
      technique can improve image contrast with aids of 3D whole volume CT images. Even
      though local tomosynthesis needs extra 3D CT scanning, it may find clinical
      applications in special situations in which extra 3D CT scan is already available
      or allowed.

PMID- 22151539
TI  - Propensity score matching in estimating the effect of managerial education on
      academic planning behavior. Study design: a cross-sectional study.
AB  - BACKGROUND: In many academic settings teaching a particular topic is applied to
      every student enrolled in the same academic year, it is a difficult task for
      researchers to design a randomized control group study. This research aimed to
      estimate the effect of teaching management and planning on increasing academic
      planning behavior (APB), using propensity score matching (PSM). METHODS: In a
      cross-sectional survey utilizing a self-reported structured questionnaire on a
      systematic random sample of 421 students in Hanoi Medical University, one of the
      eight medical schools in Vietnam, this evaluation study adopted regression
      procedures to assess model fit, then PSM to create a matched control group in
      order to allow for evaluating the effect of management education. RESULTS: The
      study showed both direct and indirect effects of the education on behavior. After
      PSM to adjust for the possible confounders to balance statistically two groups-
      with and without management education, there is statistically a significant
      difference in APB between these two groups, making a net difference of 18.60%
      (p<.05). The estimated 18.6 percentage point increase can be translated into the
      practice of APB by 670 students in the population. This number of academic
      planners can be attributed to a high recall of important management and planning
      education. CONCLUSIONS: The study provided theoretical as well as practical
      implications to guide the design of the education and evaluation of teaching.

PMID- 22151540
TI  - Matrix metalloproteinase-9 expression in the nuclear compartment of neurons and
      glial cells in aging and stroke.
AB  - Matrix metalloproteinases (MMPs) are well-recognized denominators for
      extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic
      strokes. Recent data on non-nervous system tissue showed intracellular and even
      intranuclear localizations for different MMPs, and together with this, a plethora
      of new functions have been proposed for these intracellular active enzymes, but
      are mostly related to apoptosis induction and malign transformation. In neurons
      and glial cells, on human tissue, animal models and cell cultures, different
      active MMPs have been also proven to be located in the intra-cytoplasmic or intra
      nuclear compartments, with no clear-cut function. In the present study we show
      for the first time on human tissue the nuclear expression of MMP-9, mainly in
      neurons and to a lesser extent in astrocytes. We have studied ischemic and
      hemorrhagic stroke patients, as well as aged control patients. Age and ischemic
      suffering seemed to be the best predictors for an elevated MMP-9 nuclear
      expression, and there was no evidence of a clear-cut extracellular proteolytic
      activity for this compartment, as revealed by intact vascular basement membranes
      and assessment of vascular densities. More, the majority of the cells expressing
      MMP-9 in the nuclear compartment also co-expressed activated-caspase 3,
      indicating a possible link between nuclear MMP-9 localization and apoptosis in
      neuronal and glial cells following an ischemic or hemorrhagic event. These
      results, besides showing for the first time the nuclear localization of MMP-9 on
      a large series of human stroke and aged brain tissues, raise new questions
      regarding the unknown spectrum of the functions MMPs in human CNS pathology.

PMID- 22151543
TI  - Impact of interleukin-8 gene polymorphisms and environmental factors on oral
      cancer susceptibility in Taiwan.
AB  - OBJECTIVES: Interleukin-8 (IL-8), which is an angiogenic chemokine with a high
      expression level in tumor tissues, plays important roles in developing many human
      malignancies including oral squamous cell carcinoma (OSCC). This study was
      designed to examine the association of IL-8 gene polymorphisms with the
      susceptibility and clinicopathological characteristics of OSCC. METHODS: A total
      of 270 patients with OSCC and 350 healthy control subjects were recruited. Four
      single nucleotide polymorphisms (SNPs) of IL-8 genes were analyzed using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      genotyping analysis. RESULTS: Results showed that four IL-8 SNPs (-251 T/A, +781
      C/T, +1633 C/T, and +2767 A/T) were not associated with oral cancer
      susceptibility as well as clinicopathological parameters. But among 345 smokers,
      IL-8 polymorphisms carriers with betel quid chewing were found to have a 17.41-
      to 23.14-fold risk to have oral cancer compared to IL-8 wild-type carriers
      without betel quid chewing. Among 262 betel quid chewers, IL-8 polymorphisms
      carriers with smoking have a 10.54- to 20.44-fold risk to have oral cancer
      compared to those who carried wild type without smoking. CONCLUSIONS: Our results
      suggest that the combination of IL-8 gene polymorphisms and environmental
      carcinogens might be highly related to the risk of oral cancer.

PMID- 22151541
TI  - Pathogen-origin horizontally transferred genes contribute to the evolution of
      Lepidopteran insects.
AB  - BACKGROUND: Horizontal gene transfer (HGT), a source of genetic variation, is
      generally considered to facilitate hosts' adaptability to environments. However,
      convincing evidence supporting the significant contribution of the transferred
      genes to the evolution of metazoan recipients is rare. RESULTS: In this study,
      based on sequence data accumulated to date, we used a unified method consisting
      of similarity search and phylogenetic analysis to detect horizontally transferred
      genes (HTGs) between prokaryotes and five insect species including Drosophila
      melanogaster, Anopheles gambiae, Bombyx mori, Tribolium castaneum and Apis
      mellifera. Unexpectedly, the candidate HTGs were not detected in D. melanogaster,
      An. gambiae and T. castaneum, and 79 genes in Ap. mellifera sieved by the same
      method were considered as contamination based on other information. Consequently,
      14 types of 22 HTGs were detected only in the silkworm. Additionally, 13 types of
      the detected silkworm HTGs share homologous sequences in species of other
      Lepidopteran superfamilies, suggesting that the majority of these HTGs were
      derived from ancient transfer events before the radiation of Ditrysia clade. On
      the basis of phylogenetic topologies and BLAST search results, donor bacteria of
      these genes were inferred, respectively. At least half of the predicted donor
      organisms may be entomopathogenic bacteria. The predicted biochemical functions
      of these genes include four categories: glycosyl hydrolase family, oxidoreductase
      family, amino acid metabolism, and others. CONCLUSIONS: The products of HTGs
      detected in this study may take part in comprehensive physiological metabolism.
      These genes potentially contributed to functional innovation and adaptability of
      Lepidopteran hosts in their ancient lineages associated with the diversification
      of angiosperms. Importantly, our results imply that pathogens may be advantageous
      to the subsistence and prosperity of hosts through effective HGT events at a
      large evolutionary scale.

PMID- 22151544
TI  - Biomechanical evaluation of macro and micro designed screw-type implants: an
      insertion torque and removal torque study in rabbits.
AB  - OBJECTIVE: To investigate the combined effect of macro and pitch shortened
      threads on primary and secondary stability during healing, but before dynamic
      loading. MATERIALS AND METHODS: Two sets of turned implants with different macro
      geometry were prepared. The test group possessed pitch shortened threads in
      between the large threads and the control group did not have thread alterations.
      The two implant groups were placed in both femur and tibiae of 10 lop-eared
      rabbits, and at the time of implant insertion, insertion torques were recorded.
      After 4 weeks, all implants were subjected to removal torque tests. RESULTS: The
      insertion torque values for the control and test groups for the tibia were 15.7
      and 20.6 Ncm, respectively, and for the femur, 11.8, and 12.8 Ncm respectively.
      The removal torque values for the control and test groups in the tibia were 7.9
      and 9.1 Ncm, respectively, and for the femur, 7.9 and 7.7 Ncm respectively. There
      was no statistically significant difference between the control and test groups.
      CONCLUSION: Under limited dynamic load, the addition of pitch shortened threads
      did not significantly improve either the primary or the secondary stability of
      the implants in bone.

PMID- 22151542
TI  - Immunogenicity of allogeneic mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) inhibit proliferation of allogeneic T cells and
      express low levels of major histocompatibility complex class I (MHCI), MHCII and
      vascular adhesion molecule-1 (VCAM-1). We investigated whether their
      immunosuppressive properties and low immunophenotype protect allogeneic rat MSCs
      against cytotoxic lysis in vitro and result in a reduced immune response in vivo.
      Rat MSCs were partially protected against alloantigen-specific cytotoxic T cells
      in vitro. However, after treatment with IFN-gamma and IL-1beta, MSCs upregulated
      MHCI, MHCII and VCAM-1, and cytotoxic lysis was significantly increased. In vivo,
      allogeneic T cells but not allogeneic MSCs induced upregulation of the activation
      markers CD25 and CD71 as well as downregulation of CD62L on CD4(+)  T cells from
      recipient rats. However, intravenous injection of allo-MSCs in rats led to the
      formation of alloantibodies with the capacity to facilitate complement-mediated
      lysis, although IgM levels were markedly decreased compared with animals that
      received T cells. The allo-MSC induced immune response was sufficient to lead to
      significantly reduced survival of subsequently injected allo-MSCs. Interestingly,
      no increased immunogenicity of IFN-gamma stimulated allo-MSCs was observed in
      vivo. Both the loss of protection against cytotoxic lysis under inflammatory
      conditions and the induction of complement-activating antibodies will likely
      impact the utility of allogeneic MSCs for therapeutic applications.

PMID- 22151545
TI  - Postoperative microhyphema as a positive prognostic indicator in canaloplasty.
AB  - PURPOSE: To assess risk factors for failure in canaloplasty. METHODS:  
      Nonrandomized prospective study involving 51 eyes of 51 patients with medically
      uncontrolled primary open-angle glaucoma undergoing canaloplasty. Visual acuity,
      intraocular pressure (IOP) and slit-lamp examinations were performed before and
      after surgery at 1 and 7 days, and at 1 month and every 3 months thereafter.
      Factors like age, gender, preoperative IOP and microhyphema on day 1 were
      evaluated. RESULTS:   The mean follow-up was 20.6 (SD 8.3) months. The mean
      preoperative IOP was 26.8 (SD 5.2) mmHg; the mean postoperative IOP was 8.4 (4.2)
      mmHg at day 1 and 12.7 (1.7) mmHg at month 24. Microhyphema was found in 40
      patients (85.1%) on day 1 after surgery. The height of microhyphema was 1.8 mm +/
      0.4 (SD) (range 1-2.5), and the time of resorption was 6.6 days +/- 2.8 (SD)
      (range 3-14) on average. No recurrence of hyphema has been observed. IOP < 16
      mmHg without medications depended significantly on the presence of microhyphema
      (hazard ratios, HR 0.03, 95% CI 0.01-0.25, p < 0.001), but not on age (HR 1.00,
      95% CI 0.91-1.09, p = 0.32), preoperative IOP (HR 0.98, 95% CI 0.85-1.12, p =
      0.80), cup-to-disc ratio (HR 0.15, 95% CI 0.00-20.01, p = 0.45) and gender (HR
      0.24, 95% CI 0.05-1.12, p = 0.07). Factors like preoperative IOP, age, gender,
      cup-to-disc ratio were not associated with microhyphema. There were no
      significant differences between patients with versus without microhyphema in
      regard to age, preoperative IOP, morphological and functional glaucomatous
      damage, number of medications and postoperative day 1 IOP. However, patients with
      microhyphema had significantly fewer Nd:YAG goniopunctures after surgery than
      patients without microhyphema (p < 0.001). CONCLUSION: Microhyphema the first
      postoperative day seems to be a significant positive prognostic indicator in
      uneventful canaloplasty in regard to IOP reduction, possibly representing a
      restored and patent physiologic aqueous outflow system.

PMID- 22151546
TI  - Interventions to prevent substance use and risky sexual behaviour in young
      people: a systematic review.
AB  - AIMS: To identify and assess the effectiveness of experimental studies of
      interventions that report on multiple risk behaviour outcomes in young people.
      METHODS: A systematic review was performed to identify experimental studies of
      interventions to reduce risk behaviour in adolescents or young adults and that
      reported on both any substance (alcohol, tobacco and illicit drug) use and sexual
      risk behaviour outcomes. Two authors reviewed studies independently identified
      through a comprehensive search strategy and assessed the quality of included
      studies. The report was prepared in accordance with the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: From 1129
      papers, 18 experimental studies met our inclusion criteria, 13 of which were
      assigned a strong or moderate quality rating. The substantial heterogeneity
      between studies precluded the pooling of results to give summary estimates.
      Intervention effects were mixed, with most programmes having a significant effect
      on some outcomes, but not others. The most promising interventions addressed
      multiple domains (individual and peer, family, school and community) of risk and
      protective factors for risk behaviour. Programmes that addressed just one domain
      were generally less effective in preventing multiple risk behaviour. CONCLUSIONS:
      There is some, albeit limited, evidence that programmes to reduce multiple risk
      behaviours in school children can be effective, the most promising programmes
      being those that address multiple domains of influence on risk behaviour.
      Intervening in the mid-childhood school years may have an impact on later risk
      behaviour, but further research is needed to determine the effectiveness of this
      approach.

PMID- 22151547
TI  - Spinal Cord Stimulation vs. Conventional Medical Management: A Prospective,
      Randomized, Controlled, Multicenter Study of Patients with Failed Back Surgery
      Syndrome (PROCESS Study).
AB  - Introduction.  Since its first application in 1967, numerous case series indicate
      that spinal cord stimulation (SCS) is an effective treatment for the management
      of failed back surgery syndrome (FBSS). However, only one randomized controlled
      trial has demonstrated that SCS provides more effective pain relief than re
      operation and conventional medical management. The PROCESS randomized,
      controlled, multicenter trial aims to assess the clinical effectiveness and cost
      effectiveness of SCS when added to conventional medical management compared to
      conventional medical management alone in patients with FBSS. Methods/Design.  A
      total of 100 FBSS patients with predominantly neuropathic leg pain will be
      recruited from 12 centers and randomized to receive either conventional medical
      management alone or in combination with SCS for a period of 24 months. Patients
      will be evaluated at 1, 3, 6, 9, 12, 18, and 24 months. At the 6-month visit,
      patients will be classified as successful (>=  50% pain relief in the legs) or
      unsuccessful (< 50% pain relief in the legs). If the results of the randomized
      treatment are unsuccessful, patients can cross over to the alternative treatment
      arm. Discussion.  This paper highlights the rationale, design, methods, and
      challenges of an ongoing prospective, randomized, controlled, multicenter
      clinical trial that has been undertaken to obtain conclusive evidence of the
      clinical efficacy and cost-effectiveness of an SCS system in patients with FBSS.

PMID- 22151548
TI  - Evaluation of a dual quadripolar surgically implanted spinal cord stimulation
      lead for failed back surgery patients with chronic low back and leg pain.
AB  - Objectives.  Recent publications on dual program spinal cord stimulation (SCS)
      system demonstrate more flexible electrode programming, which helps to steer
      paresthesias towards all of the affected areas including the low back area.
      Materials and Methods.  The following data were retrospectively sought from 20
      nonrandomized failed back surgery patients at two centers treated by a dual
      quadripolar surgically implanted SCS lead: pain and paresthesia, VAS ratings,
      medication use, sleep patterns, daily activities, hardware problems, and
      willingness to repeat the procedure. The data were analyzed by the Wilcoxon
      signed rank test (p value < 0.05). Results.  The average paresthesia coverage was
      76%. After SCS implantation, analgesic use was decreased in 59% of the patients,
      sleeping time augmented, and quality of sleep improved. The number of patients
      taking benzodiazepines decreased. Sixty percent reported increased participation
      in social activities. Conclusions.  This dual program surgical SCS technique is
      simple, respects patients' autonomy, and provides adequate analgesia with an
      increase in quality of life.

PMID- 22151549
TI  - Peripheral nerve stimulation inhibits nociceptive processing: an
      electrophysiological study in healthy volunteers.
AB  - Objectives.  Electric peripheral nerve stimulation (PNS) is a neuromodulatory
      therapy in pain patients. The efficacy of this neurosurgical pain treatment is
      controversial because its antinociceptive effect in humans has not been
      objectively proven so far. Materials and Methods.  Noxious infrared laser
      stimulation of the left hand dorsum evoked cortical potentials (LEP) by selective
      excitation of Adelta-fiber nociceptors in 15 healthy volunteers under control and
      PNS conditions. LEP were recorded before, during, and after electric Abeta-fiber
      stimulation (PNS) of the left superficial radial nerve. In the control session
      LEP were recorded without PNS. Laser stimulus intensity ratings, LEP latencies,
      and amplitudes were statistically analyzed (anova). Results.  During PNS, LEP
      amplitudes (p < 0.001) and laser intensity ratings (p < 0.05) significantly
      decreased, and LEP latencies significantly increased (p < 0.05). Under control
      conditions LEP and intensity ratings remained unchanged. Conclusions.  The
      electrophysiologic data provide evidence that electric stimulation of peripheral
      Abeta-fibers reliably suppresses Adelta-fiber nociceptive processing in human
      volunteers.

PMID- 22151550
TI  - An unusual sign of catheter migration: sciatica.
AB  - Implantation of an intrathecal infusion pump is now accepted as a valuable
      technique to treat chronic pain. The most frequently reported complications
      associated with it are catheter fractures or migrations, usually resulting in a
      recurrence of pain and the onset of withdrawal symptoms. Recently, the neurologic
      complication of development of a catheter-tip mass has been observed. The unusual
      complication of intradural catheter migration responsible for sciatica is
      presented here. Treatment consisted of catheter replacement, leading to immediate
      disappearance of the sciatica.

PMID- 22151551
TI  - Epileptic discharges in a mammillary body of a patient with refractory epilepsy.
AB  - Objectives.  To document epileptiform discharges recorded within a mammillary
      body (MB) of a patient with chronic refractory epilepsy (CRE). Materials and
      Methods.  A 37-year-old man, whose epilepsy was not controlled by medication or
      vagus nerve stimulation, was enrolled in a study of the effects of deep brain
      stimulation of the MB and mammillothalamic tract (MTT) in CRE. Surface and deep
      EEG recordings were obtained for 3 days before implantation of the
      macroelectrodes and for 4 days after implantation of the macroelectrodes but
      before implantation of the stimulator battery. Results.  Paroxysmal epileptiform
      discharges were recorded in the right MB while other surface and deep recordings,
      in particular from the right MTT, were silent. When these discharges were longer
      than 100 sec, they spread to the right MTT area and then to the left MB and MTT
      area. Simultaneously, the patient became agitated and confused. Conclusions. 
      This original observation indicates that subcortical neuronal structures, such as
      the MB, may sustain epileptiform discharges in humans.

PMID- 22151552
TI  - Peripheral neurostimulation in the management of cervicogenic headache: four case
      reports.
AB  - Introduction.  Neuromodulation, mediated by invasive electric stimulation, has
      been shown to be effective when applied to patients with refractory and
      intractable neuropathic pain. Recent advances in neurostimulation have broadened
      the therapeutic uses of this therapy, with the placement of extraspinal
      electrodes for peripheral nerve stimulation. Methods.  Four patients with long
      evolving, persistent, severe, uncontrolled, and localized pain in the occipital
      region, in whom other management options had been tried and failed, were treated
      with a peripheral, occipital, extraspinal electric stimulation (C1-C2-C3). We
      present, as case reports, the results of this intervention in these four
      patients. Results.  In all cases, stimulation of the occipital region yielded
      good or very good global results. In all patients, continuous pain disappeared,
      the frequency and severity of the episodic pain decreased, function improved, and
      restful sleep improved. As a result of stimulation we were either able to reduce
      or discontinue medication usage in all of our patients.

PMID- 22151553
TI  - A new neuroimplantable device: the tulgar implant. Initial results of animal
      testing.
AB  - A new neuroimplant system, namely the Tulgar implant, developed to solve the
      practical problems encountered with the presently available implants, was tested
      as a spinal cord stimulator in ten sheep. The response of living tissue and
      technical performance of the new system were evaluated. Electrodes implanted in
      the low thoracic (T9-10) vertebral levels by means of hemilaminectomy were
      subcutaneously connected to the passive coil receiver element located in the
      anterior-inferior chest wall for 28 days. Laboratory parameters including
      hematology, biochemistry, and microbiology were investigated over the study, and
      histopathologic examinations were done by the end of study. Animal tests showed
      that the new system could reliably be implantable in the living tissue. Intra
      operative radicular stimulation of the right dorsal root in T13-L1 levels, by
      means of burst mode of signals, resulted in observable contractions of hip
      muscles in the right upper leg.

PMID- 22151554
TI  - Chemical Stability of Admixtures Combining Ziconotide with Morphine or
      Hydromorphone During Simul ated Intrathecal Administration.
AB  - Objective.  To determine the stability of admixtures combining ziconotide with
      morphine or hydromorphone under simulated intrathecal infusions. Materials and
      Methods.  Admixtures of ziconotide (25 ug/mL) with morphine or hydromorphone
      (both at 35 mg/mL) were stored in Medtronic SynchroMed(r) II pumps at 37 degrees
      C, and in control vials at 37 degrees C and 5 degrees C. Drug concentrations were
      determined using high-performance liquid chromatography. Results.  The ziconotide
      pump concentration with morphine declined to 79% of initial in 17 days, and to
      88% of initial after 25 days with hydromorphone. Ziconotide concentrations in
      control vials stored at 37 degrees C displayed similar rates of decay, but vials
      stored at 5 degrees C exhibited no ziconotide loss. A statistical evaluation of
      the two combinations shows ziconotide-hydromorphone retaining 80% stability for
      40 days (extrapolated), compared to 15 days for ziconotide-morphine. Morphine and
      hydromorphone were stable in the presence of ziconotide under all conditions.
      Conclusions.  Ziconotide-hydromorphone admixtures were more stable than
      ziconotide-morphine admixtures.

PMID- 22151555
TI  - Speed and efficiency in walking and wheeling with novel stimulation and bracing
      systems after spinal cord injury: a case study.
AB  - To compare various novel and conventional systems for locomotion, a 25-year-old
      man was studied with motor complete spinal cord injury at the T4/5 level. He used
      various devices in the community, and changes in speed, physiological cost index
      (PCI), and oxygen consumption were measured periodically. Speed was fastest with
      a conventional manual wheelchair (nearly 120 m/min in a 4-min test). Speed was
      about 30% less, but the PCI was lowest (highest efficiency) using functional
      electrical stimulation (FES) of the quadriceps and hamstring muscles to propel a
      novel wheelchair. He walked with knee-ankle-foot orthoses (KAFO) at much lower
      speed (8.8 m/min) and higher PCI. He walked with an alternating gait using a new
      stance-control KAFO with FES. The speed was still slow (5 m/min), but he prefers
      the more normal-looking gait and uses it daily. Walking with FES and ankle-foot
      orthoses (AFO) was slowest (3.5 m/min) and had the highest PCI. In conclusion,
      the leg-propelled wheelchair provides a more efficient method of locomotion. A
      new stance-controlled KAFO with FES may provide a more acceptable walking system,
      but must be tested on other subjects.

PMID- 22151558
TI  - The multiple meanings of "wheezing": a questionnaire survey in Portuguese for
      parents and health professionals.
AB  - BACKGROUND: Most epidemiological studies on pediatric asthma rely on the report
      of "wheezing" in questionnaires. Our aim was to investigate the understanding of
      this term by parents and health professionals. METHODS: A cross-sectional survey
      was carried out in hospital and community settings within the south of Portugal.
      Parents or caregivers self-completed a written questionnaire with information on
      social characteristics and respiratory history. Multiple choice questions
      assessed their understanding of "wheezing". Health professionals (physicians,
      nurses and physiotherapists) were given an adapted version. We used bivariate
      analysis and multivariate models to study associations between definitions of
      "wheezing" and participants' characteristics. RESULTS: Questionnaires from 425
      parents and 299 health professionals were included. The term "wheezing" was not
      recognized by 34% of parents, more frequently those who were younger (OR 0.4 per
      10-year increment, 95% CI 0.3-0.7), had lower education (OR 3.3, 95% CI 1.5-7.4),
      and whose children had no history of respiratory disease (OR 4.6, 95% CI 2.5-8.7)
      (all ORs adjusted). 31% of parents familiar with "wheezing" either did not
      identify it as a sound, or did not locate it to the chest, while tactile (40%)
      and visual (34%) cues to identify "wheezing" were frequently used. Nurses
      reported using visual stimuli and overall assessments more often than physicians
      (p < 0.01). The geographical location was independently associated with how
      parents recognized and described "wheezing". CONCLUSIONS: Different meanings for
      "wheezing" are recognized in Portuguese language and may be influenced by
      education, respiratory history and regional terminology. These findings are
      likely applicable to other non-English languages, and suggest the need for more
      accurate questionnaires and additional objective measurement instruments to study
      the epidemiology of wheezing disorders.

PMID- 22151559
TI  - Effects of forest plantations on the genetic composition of conspecific native
      Aleppo pine populations.
AB  - Afforestation is a common and widespread management practice throughout the
      world, yet its implications for the genetic diversity of native populations are
      still poorly understood. We examined the effect of Aleppo pine (Pinus halepensis)
      plantations on the genetic composition of nearby conspecific native populations.
      We focused on two native populations in Israel with different levels of isolation
      from the surrounding plantations and compared the genetic diversity of naturally
      established young trees within the native populations with that of local native
      adults, using nine nuclear microsatellite markers. We found that the genetic
      composition of the recruits was significantly different from that of local adults
      in both populations, with allelic frequency changes between generations that
      could not be ascribed to random drift, but rather to substantial gene flow from
      the surrounding planted Aleppo pine populations. The more isolated population
      experienced a lower gene-flow level (22%) than the less isolated population
      (49%). The genetic divergence between native populations at the adult-tree stage
      (F(st) = 0.32) was more than twice as high as that of the young trees naturally
      established around native adults (F(st) = 0.15). Our findings provide evidence
      for a rapid genetic homogenization process of native populations following the
      massive planting efforts in the last decades. These findings have important
      implications for forest management and nature conservation and constitute a
      warning sign for the risk of translocation of biota for local biodiversity.

PMID- 22151560
TI  - An in vitro model for the study of human implantation.
AB  - PROBLEM: Implantation remains the rate-limiting step for the success of in vitro
      fertilization. Appropriate models to study the molecular aspects of human
      implantation are necessary in order to improve fertility. METHODS: First
      trimester trophoblast cells are differentiated into blastocyst-like spheroids
      (BLS) by culturing them in low attachment plates. Immortalized human endometrial
      stromal cells and epithelial cells (ECC-1) were stably transfected with GFP or
      tdTomato. Co-culture experiments were monitored using Volocity imaging analysis
      system. RESULTS: This method demonstrates attachment and invasion of BLS, formed
      by trophoblast cells, into stromal cells, but not to uterine epithelial cells.
      CONCLUSION: We have developed an in vitro model of uterine implantation. The
      manipulation of this system allows for dual color monitoring of the cells over
      time. Additionally, specific compounds can be added to the culture media to test
      how this may affect implantation and invasion. This model is a helpful tool in
      understanding the complexity of human implantation.

PMID- 22151561
TI  - Perceptual embodiment of prosthetic limbs by transcutaneous electrical nerve
      stimulation.
AB  - OBJECTIVES:   In able-bodied participants, it is possible to induce a sense of
      perceptual embodiment in an artificial hand using a visual-tactile illusion. In
      amputee patients, electrical stimulation of sensory afferents using
      transcutaneous electrical nerve stimulation (TENS) has been shown to generate
      somatic sensations in an amputee's phantom limb(s). However, the effects of TENS
      on the perceptual embodiment of an artificial limb are not known. Our objective
      was to investigate the effects of TENS on the perceptual embodiment of an
      artificial limb in fully intact able-bodied participants. MATERIALS AND METHODS: 
      We used a modified version of the rubber hand illusion presented to 30 able
      bodied participants (16 women, 14 men) to convey TENS paresthesia to an
      artificial hand. TENS electrodes were located over superficial radial nerve on
      the lateral aspect of the right forearm (1 cm proximal to the wrist), which was
      hidden from view. TENS intensity was increased to a strong non-painful TENS
      sensation (electrical paresthesia) was felt beneath the electrodes and projecting
      into the fingers of the hand. The electrical characteristics of TENS were
      asymmetric biphasic electrical pulsed waves, continuous pulse pattern, 120 Hz
      pulse frequency (rate), and 80 us pulse duration (width). RESULTS:   Participants
      reported significantly higher intensities of the rubber hand illusion during the
      two TENS conditions (mean = 5.8, standard deviation = 1.9) compared with the two
      non-TENS conditions (mean = 4.9, standard deviation = 1.7), p < 0.0005.
      CONCLUSIONS:   Our findings provide initial evidence that TENS paresthesia can be
      projected into an artificial limb, and this can enhance the sense of perceptual
      embodiment of an artificial hand. Further exploratory studies involving an
      amputee population are warranted.

PMID- 22151562
TI  - Angioplasty and stenting of a jugular-carotid fistula resulting from the
      inadvertent placement of a hemodialysis catheter: case report and review of
      literature.
AB  - Hemodialysis catheterization through the right internal jugular vein (IJV) is
      widely used for mid- to long-term hemodialysis for patients with renal failure.
      The purpose of this report is to address a serious complication in conjunction
      with this procedure. This is a case report of an iatrogenic jugular-carotid
      fistula (JCF) and a method for rectifying such a vascular conundrum, using
      endovascular techniques. We describe the technique used to achieve closure of the
      fistula as well a review of the literature. An 82-year-old woman with history of
      congestive heart failure, chronic renal failure, and diabetes mellitus developed
      an iatrogenic arteriovenous fistula, following an attempt of canalizing the right
      IJV. The patient was treated using three different stents, which achieved closure
      of the fistula. Venous catheter misplacement into an artery is a serious
      complication. Early endovascular treatment should be considered for a JCF.

PMID- 22151564
TI  - The SWIFT Cast trial protocol: a randomized controlled evaluation of the efficacy
      of an ankle-foot cast on walking recovery early after stroke and the neural
      biomechanical correlates of response.
AB  - RATIONALE: An ankle-foot cast may enable people to repeatedly practice walking
      with a more normal movement pattern early after stroke. AIMS: To evaluate the
      clinical efficacy of using an ankle-foot cast [soft scotch ankle-foot (SWIFT)
      Cast] to enhance walking recovery and to find whether site of stroke lesion
      and/or baseline biomechanical characteristics predict response to a SWIFT Cast.
      DESIGN: Randomized, controlled, observer-blind trial. STUDY: Participants (n =
      120), 3-42 days after stroke with walking difficulty. All will receive
      conventional physical therapy. Those allocated to the experimental group will
      also receive a SWIFT Cast for up to six-weeks. During therapy sessions, the SWIFT
      Cast will be worn for retraining of walking as clinically appropriate. Outside
      therapy sessions, participants will initially wear the SWIFT Cast for the whole
      of their waking day, and this will be adjusted as clinically appropriate.
      OUTCOMES: Measures will be undertaken before randomization, six-weeks thereafter
      and six-months after stroke. Primary outcome will be walking speed. Secondary
      outcomes will include the Functional Ambulation Category and efficiency of gait
      (e.g. step-time symmetry). Structural brain imaging using magnetic resonance
      imaging (standard fluid attenuated inversion recovery and T1-weighted high
      resolution 'volume' spoiled gradient) will be undertaken at baseline. The
      clinical efficacy analysis will use analysis of covariance. The relationship
      between clinical response to therapy and biomechanical data will use correlation
      and multivariate regression techniques as required. For neuroimaging data, the
      relationship to clinical response to therapy will be computed using voxel-based
      lesion-symptom mapping. An interaction test across groups will identify which
      voxels are associated with different mean levels of treatment efficacy.

PMID- 22151565
TI  - Spinal cord stimulation for failed back surgery syndrome.
AB  - Objective. The purpose of this study is to evaluate the effectiveness of modern
      spinal cord stimulation (SCS) for the treatment of failed back surgery syndrome
      (FBSS). Materials and Methods. Thirty patients were treated with SCS between
      December 1992 and January 1998 for low back and radicular pain after multiple
      failed back surgeries. Permanent systems were implanted if trial stimulation led
      to > 50% pain reduction. Median long-term follow-up was 34 months (range, 6-66
      months). Severity of pain was determined postoperatively by a disinterested third
      party. Results. Overall, 12 of the 16 patients (75%) who received permanent
      implants continued to report at least 50% relief of pain at follow-up. All six
      patients who underwent placement of laminectomy-styled electrode for SCS in the
      thoracic region had > 50% pain relief at long-term follow-up. Visual analog
      scores decreased an average of 3.2 (from 8.6 preoperatively to 5.4
      postoperatively). Patients undergoing SCS placement via laminectomy in the
      thoracic region experienced an average decrease of 4.9 in VAS, whereas those who
      underwent percutaneous placement of thoracic leads had an average decrease of
      2.5. Conclusions. SCS is an effective treatment for chronic low back and lower
      extremity pain which is refractory to conservative therapy and which is not
      amenable to corrective anatomic surgery. Though our patient population is small,
      our results imply that the laminectomy-style electrodes in the thoracic region
      achieve better long-term effectiveness than percutaneous leads.

PMID- 22151566
TI  - Outcomes of spinal cord stimulation: patient validation.
AB  - Objective. To identify aspects of daily life that have been most affected by
      chronic low back pain among spinal cord stimulation (SCS) patients and to
      determine the relative contribution that improvement in each would make to
      patients' quality of life (QOL). Materials and Methods. Telephone survey of 44
      patients with chronic low back pain who were about to undergo or had been
      recently implanted with an SCS system. Patients were asked to define, by open
      ended response and examiner-read list, those aspects of daily life that had been
      most affected by pain and to assess the relative importance that improvement in
      each would make to daily life. Results. Patients identified 13 areas of daily
      function that were most significantly impacted by chronic low back pain. Most
      frequently, activities of daily living, decreased ability to work, psychological
      changes, and limitations to social life and recreation were identified.
      Functional status change, decreased ability to walk, and ability to perform daily
      household activities were rated as the most important change from among items
      included in examiner-read list. Conclusions. Patients with chronic low back pain
      seek improvement in multiple dimensions of QOL after SCS, particularly increased
      physical activity, social relations, work status, and mood. It is likely that
      patients' assessment of SCS "success" correlates highly with functional
      improvement. As such, an understanding of SCS therapeutic benefit and
      satisfaction requires that QOL be carefully assessed in future outcome trials.

PMID- 22151567
TI  - Selective Nerve Root Stimulation (SNRS) for the Treatment of Intractable Pelvic
      Pain and Motor Dysfunction: A Case Report.
AB  - Interstitial cystitis is the most disabling nonmalignant disorder seen by
      urologists. Chronic debilitating urinary bladder symptoms (severe pain and pelvic
      floor muscular dysfunction) often progress despite maximal medical attempts at
      management. Although the exact cause remains unknown, a neuropathic etiology has
      recently been suggested( 1,2). This case report describes the use of Selective
      Nerve Root Stimulation (SNRS) for the treatment of intractable pelvic pain and
      motor dysfunction in a patient with Interstitial cystitis (IC).

PMID- 22151569
TI  - Letter to the editor.

PMID- 22151568
TI  - Methadone in the intrathecal treatment of chronic nonmalignant pain resistant to
      other neuroaxial agents: the first experience.
AB  - Intrathecal drug delivery is a widely used and effective method of treatment for
      chronic intractable pain. Unfortunately all currently used agents can not provide
      adequate pain relief in all patients. A prospective study of neuroaxial methadone
      was performed in 24 patients, all of whom had failed treatment with multiple
      previous intrathecal drugs. Thirteen patients experienced improvement of their
      pain control with methadone, nine continued to receive this agent for 6 months
      with good pain relief, improved quality of life and no side effects. The final
      rates of methadone infusion were 2.2 times higher than preceding morphine rates.
      The only observed possible side effect of methadone was transient blurred vision
      in one patient. Methadone is a promising alternative neuroaxial agent in the
      treatment of chronic pain.

PMID- 22151570
TI  - Reply to letter to the editor (2000;3:159-160).

PMID- 22151571
TI  - Control of ankle and hip joint stiffness for arm-free standing in paraplegia.
AB  - Objective. To investigate whether a simple static stiffness model adequately
      relates the angles and net joint torques (NJT) developed in the ankles (sagittal
      plane) and in the hips (frontal plane) following perturbations delivered in
      multiple directions to partially constrained subjects standing quietly. Materials
      and Methods. Six subjects were standing on two force platforms while an apparatus
      randomly delivered controlled perturbations at the level of pelvis in eight
      directions in the transverse plane. Results. Ankle sum stiffness was found to be
      invariant of the perturbation directions for the group of forward directed
      perturbations (17 +/- 5 Nm/deg, p= 0.93) as well as for the group of backward
      directed perturbations (13 +/- 6 Nm/deg, p= 0.92). The correlation coefficients
      were confined between 0.95 and 0.98 across perturbation directions. Hip sum
      stiffness was found to be invariant of the perturbation directions (15 +/- 4
      Nm/deg, p= 0.98). The correlation coefficients were confined between 0.96 and
      0.98 across perturbation directions. Conclusions. The relationship between the
      ankle angles and NJT and hip angles and NJT following perturbed stance can be
      described as static stiffness. The implications for arm-free paraplegic standing
      are discussed and a new control scheme is proposed.

PMID- 22151572
TI  - Bacterial species may exist, metagenomics reveal.
AB  - Whether or not bacterial species exist remains an unresolved issue of paramount
      theoretical as well as practical consequences. Here we review and synthesize the
      findings emerging from metagenomic surveys of natural microbial populations and
      argue that microbial communities are predominantly organized in genetically and
      ecologically discernible populations, which possess the attributes expected for
      species. These sequence-discrete populations represent a major foundation for
      beginning high-resolution investigations on how populations are organized,
      interact, and evolve within communities. We also attempt to reconcile these
      findings with those of previous studies that reported indiscrete species and a
      genetic continuum within bacterial taxa and discuss the implications for the
      current bacterial species definition.

PMID- 22151573
TI  - openBIS: a flexible framework for managing and analyzing complex data in biology
      research.
AB  - BACKGROUND: Modern data generation techniques used in distributed systems biology
      research projects often create datasets of enormous size and diversity. We argue
      that in order to overcome the challenge of managing those large quantitative
      datasets and maximise the biological information extracted from them, a sound
      information system is required. Ease of integration with data analysis pipelines
      and other computational tools is a key requirement for it. RESULTS: We have
      developed openBIS, an open source software framework for constructing user
      friendly, scalable and powerful information systems for data and metadata
      acquired in biological experiments. openBIS enables users to collect, integrate,
      share, publish data and to connect to data processing pipelines. This framework
      can be extended and has been customized for different data types acquired by a
      range of technologies. CONCLUSIONS: openBIS is currently being used by several
      SystemsX.ch and EU projects applying mass spectrometric measurements of
      metabolites and proteins, High Content Screening, or Next Generation Sequencing
      technologies. The attributes that make it interesting to a large research
      community involved in systems biology projects include versatility, simplicity in
      deployment, scalability to very large data, flexibility to handle any biological
      data type and extensibility to the needs of any research domain.

PMID- 22151574
TI  - Tauroursodeoxycholic acid enhances the pre-implantation embryo development by
      reducing apoptosis in pigs.
AB  - Apoptosis is an important determinant of the normal development of pre
      implantation embryos in vitro. Recently, endoplasmic reticulum (ER) stress
      mediated apoptosis has been extensively investigated in a wide variety of
      diseases. Efficient functioning of the ER is essential for most cellular
      activities and survival. Tauroursodeoxycholic acid (TUDCA), an endogenous bile
      acid, has been reported to attenuate ER stress-mediated cell death by
      interrupting the classic pathways of apoptosis. Therefore, in this study, the
      anti-apoptotic effect of TUDCA on ER stress-induced apoptosis was examined in pre
      implantation pig embryos. Also, tunicamycin was used to investigate the effects
      of ER stress on pig embryo development. After in vitro maturation and
      fertilization, presumptive pig embryos were cultured in NCSU-23 medium
      supplemented with TUDCA or TM for 6 days at 39  degrees C, 5% CO(2) in air. All
      data were analysed using one-way anova and Duncan's multiple range test in the
      statistical analysis system (SAS). In addition, we also determined the optimal TM
      and TUDCA concentrations. Samples were treated with TM at concentrations of 0, 1,
      2 or 5 MUm and with TUDCA at concentrations of 0, 100, 200 or 300 MUm. When TM
      was used during in vitro culture, only 8.2% (8/97) of the embryos developed to
      the blastocyst stage when the treatment concentration was 1 MUm compared with
      27.4% (28/102) of the embryos in the control group (p < 0.05). In contrast, the
      frequency of blastocyst formation and the number of cells were higher when
      treated with 200 MUm TUDCA compared with the control group (32.8% and 39.5 vs
      22.2% and 35.6, p < 0.05). Moreover, the developmental rate to the blastocyst
      stage embryo in the group treated with TM and TUDCA was not significantly
      different from that of the control group (17.8%, 26/142 vs 24.9%, 36/145).
      Furthermore, the blastocyst cell number was enhanced (31.9 vs 36.9) and apoptosis
      reduced (TUNEL-positive nuclei number, 6.0 vs 3.2) by TUDCA treatment in pig
      embryos. In the real-time quantitative RT-PCR analysis, the expression of anti
      apoptotic Bcl-XL gene was shown to be increased in the blastocyst stage because
      of TUDCA treatment, whereas expression of pro-apoptotic Bax was decreased. In
      addition, we also found that TUDCA decreased the rate of TM-induced apoptosis in
      the pre-implantation stage. Taken together, our results indicate that TUDCA
      improves the developmental competence of pig embryos by modulating ER stress
      induced apoptosis during the pre-implantation stage.

PMID- 22151576
TI  - Burnout syndrome among dental students: a short version of the "Burnout Clinical
      Subtype Questionnaire" adapted for students (BCSQ-12-SS).
AB  - BACKGROUND: Burnout has been traditionally defined in relation to the dimensions
      of "exhaustion", "cynicism", and "inefficiency". More recently, the Burnout
      Clinical Subtype Questionnaire (BCSQ-12) further established three different
      subtypes of burnout: the "frenetic" subtype (related to "overload"), the "under
      challenged" subtype (related to "lack of development"), and the "worn-out"
      subtype (related to "neglect"). However, to date, these definitions have not been
      applied to students. The aims of this research were (1) to adapt a Spanish
      version of the BCSQ-12 for use with students, (2) to test its factorial validity,
      internal consistency, convergent and discriminant validity, and (3) to assess
      potential socio-demographic and occupational risk factors associated with the
      development of the subtypes. METHOD: We used a cross-sectional design on a sample
      of dental students (n = 314) from Santiago and Huesca universities (Spain).
      Participants completed the Burnout Clinical Subtype Questionnaire Student Survey
      (BCSQ-12-SS), the Maslach Burnout Inventory Student Survey (MBI-SS), and a series
      of socio-demographic and occupational questions formulated for the specific
      purpose of this study. Data were subjected to exploratory factor analysis (EFA)
      using the principal component method with varimax orthogonal rotation. To assess
      the relations with the criterion, we calculated the Pearson correlation
      coefficient (r), multiple correlation coefficient (R(y.123)), and the coefficient
      of determination (R(2)(y.123)). To assess the association between the subtypes
      and the socio-demographic variables, we examined the adjusted odds ratio (OR)
      obtained from multivariate logistic regression models. RESULTS: Factorial
      analyses supported the theoretical proposition of the BCSQ-12-SS, with alpha
      values exceeding 0.80 for all dimensions. The "overload-exhaustion" relation was
      r = 0.59 (p < 0.001), "lack of development"-"cynicism", r = 0.49 (p < 0.001),
      "neglect"-"inefficiency", r = 0.47 (p < 0.001). The "overload"-"lack of
      development" relation was r = 0.21 (p < 0.001), "overload"-"neglect", r = 0.20 (p
      < 0.001), and "lack of development"-"neglect", r = 0.38 (p < 0.001). The BCSQ-12
      SS explained 38.44% of the variability in "exhaustion", (R(y.123) = 0.62), 30.25%
      in "cynicism" (R(y.123) = 0.55), and 26.01% in "inefficiency" (R(y.123) = 0.51).
      "Hours spent on studying" was found to be associated with "overload" (p = 0.001),
      "campus" with "lack of development" (p = 0.013), and ""failed subjects" with
      "neglect" (p = 0.011). CONCLUSIONS: The results support the definition of burnout
      as established by the BCSQ-12-SS. As such, the BCSQ-12-SS can be used for the
      recognition of clinical profiles and for the suggestion of potential intervention
      strategies specific to the characteristics of each particular case.

PMID- 22151575
TI  - Clinical effectiveness of rapid tests for methicillin resistant Staphylococcus
      aureus (MRSA) in hospitalized patients: a systematic review.
AB  - BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) are often
      resistant to multiple classes of antibiotics. The research objectives of this
      systematic review were to evaluate the clinical effectiveness of polymerase chain
      reaction (PCR) versus chromogenic agar for MRSA screening, and PCR versus no
      screening for several clinical outcomes, including MRSA colonization and
      infection rates. METHODS: An electronic literature search was conducted on
      studies evaluating polymerase chain reaction techniques and methicillin (also
      spelled meticillin) resistant Staphylococcus aureus that were published from 1993
      onwards using Medline, Medline In-Process & Other Non-Indexed Citations, BIOSIS
      Previews, and EMBASE. Due to the presence of heterogeneity in the selected
      studies, the clinical findings of individual studies were described. RESULTS:
      Nine studies that compared screening for MRSA using PCR versus screening using
      chromogenic agar in a hospital setting, and two studies that compared screening
      using PCR with no or targeted screening were identified. Some studies found lower
      MRSA colonization and acquisition, infection, and transmission rates in screening
      with PCR versus screening with chromogenic agar, and the turnaround time for
      screening test results was lower for PCR. One study reported a lower number of
      unnecessary isolation days with screening using PCR versus screening with
      chromogenic agar, but the proportion of patients isolated was similar between
      both groups. The turnaround time for test results and number of isolation days
      were lower for PCR versus chromogenic agar for MRSA screening. CONCLUSIONS: The
      use of PCR for MRSA screening demonstrated a lower turnaround time and number of
      isolation days compared with chromogenic agar. Given the mixed quality and number
      of studies (11 studies), gaps remain in the published literature and the evidence
      remains insufficient. In addition to screening, factors such as the number of
      contacts between healthcare workers and patients, number of patients attended by
      one healthcare worker per day, probability of colonization among healthcare
      workers, and MRSA status of hospital shared equipment and hospital environment
      must be considered to control the transmission of MRSA in a hospital setting.

PMID- 22151577
TI  - A 6-month histological analysis on maxillary sinus augmentation with and without
      use of collagen membranes over the osteotomy window: randomized clinical trial.
AB  - INTRODUCTION: Over the years, several modifications have been made to the sinus
      augmentation technique and to the materials used. However, there is still
      controversy about the need for using a barrier concurrently with a graft in sinus
      augmentation procedures. On this basis, the aim of this randomized clinical study
      was to investigate the effect of resorbable collagen membrane over the osteotomy
      window on maxillary sinus augmentation healing. MATERIALS AND METHODS: Patients
      who required maxillary sinus augmentation were evaluated and selected to enter
      the study. After maxillary sinus grafting, each patient was randomly assigned to
      control (membrane over the osteotomy window) or test (no membrane) group. After 6
      months, one bone biopsy was harvested from the lateral window and sent to the
      histology laboratory. The Mann-Whitney nonparametric test was used for comparing
      the two groups. P-value was set at 5%. RESULTS: Eighteen patients entered the
      study and were randomly allocated in control (nine patients) or test group (nine
      patients). The histomorphometric measurements revealed that newly formed bone was
      30.7% +/- 15.5% of the total volume from the membrane group (control). The
      average percentage of connective tissue was 50.6% +/- 18.7% and residual graft
      percentage was 18.4% +/- 20.3%. On the other hand, data regarding the nonmembrane
      group (test) showed that the percentage of newly formed bone was 28.1% +/- 19.4%.
      The mean percentage of connective tissues was 59.3% +/- 15.4% and 12.6% +/- 12.4%
      for the residual graft particles. No significant difference was detected in the
      histomorphometrical evaluation between the two groups. DISCUSSION: Our results
      showed that, compared with sites not covered, the use of the membrane did not
      substantially increase the amount of vital bone over a period of 6 months. On the
      other hand, the use of membrane seems to reduce the proliferation of the
      connective tissue and the graft re-absorption rate. It is plausible that blood
      supply of maxillary sinus can play a role in such a result. Further studies are
      needed to explore whether the use of membrane could really be advantageous for
      the sinus augmentation procedure and to evaluate what influence this method can
      have on the amount and quality of reconstructed bone.

PMID- 22151578
TI  - Gender relations and health research: a review of current practices.
AB  - INTRODUCTION: The importance of gender in understanding health practices and
      illness experiences is increasingly recognized, and key to this work is a better
      understanding of the application of gender relations. The influence of
      masculinities and femininities, and the interplay within and between them
      manifests within relations and interactions among couples, family members and
      peers to influence health behaviours and outcomes. METHODS: To explore how
      conceptualizations of gender relations have been integrated in health research a
      scoping review of the existing literature was conducted. The key terms gender
      relations, gender interactions, relations gender, partner communication,
      femininities and masculinities were used to search online databases. RESULTS:
      Through analysis of this literature we identified two main ways gender relations
      were integrated in health research: a) as emergent findings; and b) as a basis
      for research design. In the latter, gender relations are included in conceptual
      frameworks, guide data collection and are used to direct data analysis.
      CONCLUSIONS: Current uses of gender relations are typically positioned within
      intimate heterosexual couples whereby single narratives (i.e., either men or
      women) are used to explore the influence and/or impact of intimate partner gender
      relations on health and illness issues. Recommendations for advancing gender
      relations and health research are discussed. This research has the potential to
      reduce gender inequities in health.

PMID- 22151579
TI  - Cardiovascular risk assessment of South Asians in a religious setting: a
      feasibility study.
AB  - AIMS: South Asians in the UK have high cardiovascular disease (CVD) mortality.
      Therefore, this population is likely to benefit from screening programmes. To
      address this issue, an initiative was set up between the Royal Free Hampstead NHS
      Trust, H.E.A.R.T. UK and two Hindu temples in North London to provide screening
      for CVD risk factors in the community. METHODS: A total of 434 individuals of
      Gujarati Indian origin were screened. Measurements included anthropometry, blood
      pressure and lipid profiles. Three different scoring systems: Framingham, Joint
      British Societies' 2 and QRISK2 were used to estimate CVD risk. RESULTS: At least
      one modifiable CVD risk factor was present in 92% of the individuals screened;
      52% were hypertensive, 40% were obese, 75% had central adiposity and 10% had
      total cholesterol/high density lipoprotein cholesterol ratio > 6. In addition,
      37% of a subset of 104 individuals with a fasting sample fulfilled the diagnostic
      criteria for metabolic syndrome. Overall, 15% of participants screened had a 10
      year CV risk score > 20% using QRISK2. The three risk score calculators showed
      moderate agreement: QRISK2 and JBS2 (kappa 0.61, 95% CI 0.54-0.67), QRISK2 and
      Framingham (kappa 0.63, 95% CI 0.57-0.70) and JBS2 and Framingham (kappa 0.70,
      95% CI 0.64-0.75). CONCLUSIONS: A high prevalence of modifiable risk factors for
      CVD was detected in the population screened.

PMID- 22151580
TI  - Periapical tissue reactions to calcium hydroxide and MTA after external root
      resorption as a sequela of delayed tooth replantation.
AB  - Clinical experience has shown that most avulsed teeth are replanted after a long
      extra-alveolar time and dry or inadequate wet storage, causing necrosis of
      periodontal ligament cells. This condition invariably leads to development of
      external root resorption, leaving the filling material in contact with the
      periapical connective tissues. In this study, the periapical tissue reactions to
      calcium hydroxide (CH) and mineral trioxide aggregate (MTA) were evaluated after
      occurrence of external root resorption as an expected sequela of delayed tooth
      replantation. Twenty male Wistar rats (Rattus norvegicus, albinus) had their
      right upper incisor extracted and maintained in dry storage for 60 min. Then, the
      dental papilla, enamel organ, pulp tissue, and periodontal ligament were removed,
      and the teeth were immersed in a 2% acidulated phosphate sodium fluoride
      solution, pH 5.5, for 10 min. The teeth were randomly assigned into two groups (n
      = 10), in which the canals were filled with either a CH and saline paste (CH
      group) or MTA (MTA group). The sockets were irrigated with saline, and the teeth
      were replanted. After 80 days, it was possible to observe large areas of
      replacement root resorption and some areas of inflammatory root resorption in
      both groups. More severe inflammatory tissue reaction was observed in contact
      with calcium hydroxide compared with the mineral trioxide aggregate. New bone
      formation was more intense at the bottom of the socket in the MTA group. In
      conclusion, as far as periapical tissue compatibility is concerned, intracanal
      MTA can be considered as a viable option for root canal filling in delayed tooth
      replantation, in which external root resorption is an expected sequela.

PMID- 22151582
TI  - The misdiagnosis of retinoschisis.

PMID- 22151581
TI  - Isoform diversity and its importance for axon regeneration.
AB  - Axon regeneration is a fundamental problem facing neuroscientists and clinicians.
      Failure of axon regeneration is caused by both extrinsic and intrinsic
      mechanisms. New techniques to examine gene expression such as Next Generation
      Sequencing of the Transcriptome (RNA-Seq) drastically increase our knowledge of
      both gene expression complexity (RNA isoforms) and gene expression regulation. By
      utilizing RNA-Seq, gene expression can now be defined at the level of isoforms,
      an essential step for understanding the mechanisms governing cell identity,
      growth and ultimately cellular responses to injury and disease.

PMID- 22151583
TI  - Correlations and agreement between delta-9-tetrahydrocannabinol (THC) in blood
      plasma and timeline follow-back (TLFB)-assisted self-reported use of cannabis of
      patients with cannabis use disorder and psychotic illness attending the CapOpus
      randomized clinical trial.
AB  - AIMS: To assess correlations and agreement between timeline follow-back (TLFB)
      assisted self-report and blood samples for cannabis use. DESIGN: Secondary
      analysis of a randomized trial. SETTING: Copenhagen, Denmark. PARTICIPANTS: One
      hundred and three patients from the CapOpus trial with cannabis use disorder and
      psychosis, providing 239 self-reports of cannabis use and 88 valid blood samples.
      MEASUREMENTS: Delta-9-tetrahydrocannabinol (THC), 11-hydroxy-delta-9
      tetrahydrocannabinol (11-OH-THC) and 11-nor-delta-9-tetrahydrocannabinol-9
      carboxylic acid (THC-COOH) detected in plasma using high-performance liquid
      chromatography with tandem mass spectrometry detection. Self-report of cannabis
      use last month by TLFB. Pearson's r, sensitivity and specificity calculated as
      measures of correlation or agreement. FINDINGS: Correlations were strong; r =
      0.75 for number of days and r = 0.83 for number of standard joints in the
      preceding month when excluding outliers. Including outliers, coefficients were
      moderate to strong (r = 0.49). There were differences in subgroups, mainly
      inconsistent, depending on inclusion or exclusion of outliers. Sensitivity and
      specificity for TLFB detecting the presence or absence of cannabis use were 95.7%
      [95% confidence interval (CI) 88.0-99.1%) and 72.2% (95% CI 46.5-90.3%),
      respectively. Using 19 days as cut-off on TLFB, they were 94.3% (95% CI 86.0
      98.4%) and 94.4% (95% CI 72.2-99.9%), respectively. Area under the receiver
      operating characteristic (ROC) curve was 0.96. CONCLUSIONS: Timeline follow-back
      (TLFB)-assisted self-report of cannabis use correlates highly with plasma-delta-9
      tetrahydrocannabinol in patients with comorbid cannabis use disorder and
      psychosis. Sensitivity and specificity of timeline follow-back appear to be
      optimized with 19 days as the cut-off point. As such, timeline follow-back may be
      superior to analysis of blood when going beyond 19 days of recall.

PMID- 22151584
TI  - The AMELIE project: failure mode, effects and criticality analysis: a model to
      evaluate the nurse medication administration process on the floor.
AB  - OBJECTIVE: The objective of this article was to critically evaluate the causes of
      adverse drug events during the nurse medication administration process in
      paediatric care units in order to identify and prioritize interventions that need
      to be implemented. METHODOLOGY: This is a failure mode, effects and criticality
      analysis (FMECA) study. A multidisciplinary committee composed of nurses,
      pharmacists, physicians and risk managers evaluated through consensus the process
      of administering medications at the Centre hospitalier universitaire de Sainte
      Justine. By mapping the process, all the failure modes were identified and
      associated with at least one cause each. Using a summary grid, each failure mode
      was evaluated by rating frequency (from 1 to 9), likelihood of failure detection
      (from 0 to 100%) and severity (from 1 to 9) using adapted versions of already
      published scales. RESULTS: A 10-member committee was set up, and it met eight
      times between January and April 2010. In the two specialized paediatric units
      selected (n = 38 beds), an average number of approximately 20 000 drug doses was
      administered monthly from about 400 non-proprietary names. Through consensus, the
      committee identified 16 processes and 53 failure modes. While frequency and
      severity were based on perceptions that could be objectivized with local data and
      scientific documentation, the likelihood of detection was mainly based on
      individual perception. CONCLUSION: FMECA is a useful approach to improve the
      medication process.

PMID- 22151586
TI  - General and specific components of depression and anxiety in an adolescent
      population.
AB  - BACKGROUND: Depressive and anxiety symptoms often co-occur resulting in a debate
      about common and distinct features of depression and anxiety. METHODS: An
      exploratory factor analysis (EFA) and a bifactor modelling approach were used to
      separate a general distress continuum from more specific sub-domains of
      depression and anxiety in an adolescent community sample (n = 1159, age 14). The
      Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale
      were used. RESULTS: A three-factor confirmatory factor analysis is reported which
      identified a) mood and social-cognitive symptoms of depression, b) worrying
      symptoms, and c) somatic and information-processing symptoms as distinct yet
      closely related constructs. Subsequent bifactor modelling supported a general
      distress factor which accounted for the communality of the depression and anxiety
      items. Specific factors for hopelessness-suicidal thoughts and restlessness
      fatigue indicated distinct psychopathological constructs which account for unique
      information over and above the general distress factor. The general distress
      factor and the hopelessness-suicidal factor were more severe in females but the
      restlessness-fatigue factor worse in males. Measurement precision of the general
      distress factor was higher and spanned a wider range of the population than any
      of the three first-order factors. CONCLUSIONS: The general distress factor
      provides the most reliable target for epidemiological analysis but specific
      factors may help to refine valid phenotype dimensions for aetiological research
      and assist in prognostic modelling of future psychiatric episodes.

PMID- 22151587
TI  - Toward Neurotechnology Innovation: Report from the 2005 Neural Interfaces
      Workshop. An NIH-Sponsored Event.

PMID- 22151588
TI  - Proceeding from the 9th annual meeting of the north american neuromodulation
      society.

PMID- 22151585
TI  - Chasing the hare - evaluating the phylogenetic utility of a nuclear single copy
      gene region at and below species level within the species rich group Peperomia
      (Piperaceae).
AB  - BACKGROUND: The rapidly increasing number of available plant genomes opens up
      almost unlimited prospects for biology in general and molecular phylogenetics in
      particular. A recent study took advantage of this data and identified a set of
      nuclear genes that occur in single copy in multiple sequenced angiosperms. The
      present study is the first to apply genomic sequence of one of these low copy
      genes, agt1, as a phylogenetic marker for species-level phylogenetics. Its
      utility is compared to the performance of several coding and non-coding
      chloroplast loci that have been suggested as most applicable for this taxonomic
      level. As a model group, we chose Tildenia, a subgenus of Peperomia (Piperaceae),
      one of the largest plant genera. Relationships are particularly difficult to
      resolve within these species rich groups due to low levels of polymorphisms and
      fast or recent radiation. Therefore, Tildenia is a perfect test case for applying
      new phylogenetic tools. RESULTS: We show that the nuclear marker agt1, and in
      particular the agt1 introns, provide a significantly increased phylogenetic
      signal compared to chloroplast markers commonly used for low level phylogenetics.
      25% of aligned characters from agt1 intron sequence are parsimony informative. In
      comparison, the introns and spacer of several common chloroplast markers (trnK
      intron, trnK-psbA spacer, ndhF-rpl32 spacer, rpl32-trnL spacer, psbA-trnH spacer)
      provide less than 10% parsimony informative characters. The agt1 dataset provides
      a deeper resolution than the chloroplast markers in Tildenia. CONCLUSIONS: Single
      (or very low) copy nuclear genes are of immense value in plant phylogenetics.
      Compared to other nuclear genes that are members of gene families of all sizes,
      lab effort, such as cloning, can be kept to a minimum. They also provide regions
      with different phylogenetic content deriving from coding and non-coding parts of
      different length. Thus, they can be applied to a wide range of taxonomic levels
      from family down to population level. As more plant genomes are sequenced, we
      will obtain increasingly precise information about which genes return to single
      copy most rapidly following gene duplication and may be most useful across a wide
      range of plant groups.

PMID- 22151589
TI  - STN vs. Pallidal Stimulation in Parkinson Disease: Improvement With Experience
      and Better Patient Selection.
AB  - Objectives.  This is a prospective study to determine the outcomes of subthalamic
      nucleus (STN) vs. globus pallidus internus (GPi) deep brain stimulation (DBS) at
      our institution. Materials and Methods.  We studied a total of 39 patients - 29
      with STN and 10 with GPi DBS over a period of up to 6 years. Mean ages in the two
      groups were similar (59 and 60 years, respectively) and disease duration prior to
      implantation was similar (9.6 and 11.7 years, respectively). Unified Parkinson
      Disease Rating Scale (UPDRS) was recorded preoperatively and at follow-up (at
      least at 6-month intervals). Medications also were recorded, and each patient's
      levodopa equivalent units (LEU) were calculated. Results were analyzed using a
      paired Student's t-test. Results.  LEU reduced significantly (p < 0.05) in the
      STN group (5.7 to 3.7) but not the GPi group. Both targets significantly improved
      part 3 and part 4 scores of the UPDRS but GPi DBS did not improve part 2 scores
      (activities of daily living). STN DBS had much better outcome on the motor "off"
      scores of the UPDRS, whereas GPi only improved tremor. A comparison of the
      "earliest 10" and "most recent 10" STN patients showed a significant improvement
      in outcome in the most recent cases. Conclusions.  In our group, STN was more
      effective for alleviating the symptoms of Parkinson disease, even in older
      patients with significant dyskinesias. Better patient selection and greater
      experience have led to more improvement in the more recent patients.

PMID- 22151590
TI  - Effects of bilateral extradural cortical stimulation for plegic stroke
      rehabilitation.
AB  - Objective.  We assessed the effects of bilateral extradural motor cortex
      stimulation (ECS) to areas of maximal functional MRI (fMRI) activation in a male
      patient with plegic stroke by using multiple sequential 1-month blocks of
      stimulation with single-blind design in a tertiary referral hospital.
      Measurements.  Assessments included the European Stroke Scale, Fugl-Meyer scale,
      and Barthel Index at baseline and at the end of each stimulation period, in a
      blinded fashion, over 1 year, and GABA ligand SPECT (single photon emission
      computed tomography) pre- and post-stimulation. Results.  There was modest
      improvement in nonplegic arm areas and sustained improvement of aphasia.
      Contralateral stimulation had mixed effects to the affected arm and leg.
      Conclusion.  ECS may modestly boost rehabilitation effects in a chronic stroke
      patient, with a differential effect of ipsilateral vs. contralateral stimulation.

PMID- 22151591
TI  - Neurally augmented sexual function in human females: a preliminary investigation.
AB  - Objective.  Neurally augmented sexual function (NASF) is the production of
      pleasurable genital stimulation and subsequent orgasm through the application of
      electrical energy to provide stimulation of the spinal cord or peripheral nerves.
      The purpose of this paper is to demonstrate the reproducibility of this
      phenomenon. Materials and Methods.  Eleven otherwise healthy women, ages 32-60
      years, were selected for this study. Through standard techniques, quadripolar
      (octopolar in the final patient) leads were placed in the epidural space
      percutaneuously. The lead was maneuvered initially to an L1-L2 position and then
      repositioned based on feedback from the patient. The patients were allowed to
      utilize the device ad libitum for up to 9 days. Results.  Successful stimulation
      was achieved in 91% (10/11) of patients. These women described a greater
      frequency in sexual activity, increased lubrication, and overall satisfaction. A
      smaller subset had substantial improvement in sexual function as measured by
      orgasmic capacity. This subset consisted of women with secondary anorgasmia. A
      return of orgasmic capacity was found in 80% (4/5) of patients having secondary
      anorgasmia with an average intensity of >= 3/5 while using the device. Once the
      device was removed, the patients returned to their previous anorgasmic status.
      Conclusions.  Pleasurable genital stimulation of the spinal cord is a
      consistently reproducible phenomenon. In a subset of the population studied,
      improvement in orgasmic function was noted. This was noted in the group with
      secondary orgasmic dysfunction.

PMID- 22151592
TI  - Occipital nerve stimulation for the treatment of occipital neuralgia-eight case
      studies.
AB  - Objective.  The aim of this study was to examine the hypothesis that subcutaneous
      occipital stimulation influences pain due to occipital neuralgia. Materials and
      Methods.  Between 2001 and 2004 eight patients with intractable occipital
      neuralgia were referred to our center. Their records were reviewed. Each patient
      was interviewed over the telephone. They were all offered a trial of stimulation
      using a percutaneous lead over 1 week. If they achieved 50% pain reduction a
      permanent lead was implanted. The impact of occipital stimulation was measured by
      pain score, analgesic requirements, and employment status. Results.  Seven
      proceeded to a permanent stimulator. There was a reduction in the visual analog
      score postimplantation in five of the seven patients. The total quantity of
      opiates taken after implantation showed a marked reduction. Of the seven who had
      a permanent implant two acquired full-time employment. Conclusion.  Occipital
      neuralgia is a useful and reversible treatment for intractable occipital
      neuralgia.

PMID- 22151593
TI  - Effect of electrical stimulation of hamstrings and l3/4 dermatome on gait in
      spinal cord injury.
AB  - Objective.  To determine the effect of electrical stimulation of hamstrings and
      L3/4 dermatome on the swing phase of gait. Materials and Methods.  Five subjects
      with incomplete spinal cord injury (SCI) with spasticity were included. Two
      electrical stimulation methods were investigated, i.e., hamstrings and L3/4
      dermatome stimulation. Both interventions were applied during the swing phase of
      gait. The main outcome measures were step length, maximum hip, and knee flexion
      during the swing phase of gait. In three subjects changes of spinal inhibition
      during gait were evaluated using the Hoffman reflex/m (motor)-wave (H/M) ratio at
      mid swing. Results.  The hip flexion decreased 4.6 degrees  (p < 0.05) when the
      hamstrings were stimulated during the swing phase, whereas the knee flexion was
      not changed. The step length did not change significantly. One subject showed a
      decrease of the H/M ratio to a nonpathologic level during hamstrings stimulation.
      Conclusion.  It was concluded that hamstrings stimulation during the swing phase
      results in a reduction of the hip flexion in all five SCI subjects. The H/M ratio
      of the vastus lateralis was normalized using hamstrings stimulation in one of
      three subjects. Stimulation of the L3/4 dermatome provides no significant changes
      in gait performance, but in one subject the H/M ratio increased.

PMID- 22151594
TI  - Spinal cord stimulation for axial low back pain: a prospective controlled trial
      comparing 16-contact insulated electrodes with 4-contact percutaneous electrodes.
AB  - Use of multicontact electrodes and programmable implanted pulse generators has
      increased the efficacy of spinal cord stimulation for pain. Some investigators
      find dual column electrodes advantageous for difficult-to-treat axial low back
      pain, but we have reported significantly improved measures with a single
      percutaneous midline electrode vs. dual percutaneous electrodes and even better
      results with an insulated, 1 * 4, midline electrode. In this study, 10 patients
      provided computerized, quantitative parameter measures for a temporary
      percutaneous 1 * 4 electrode and for a permanent insulated 2 * 8 electrode.
      Compared with the 2 * 8, the 1 * 4 resulted in marginally better patient-rated
      (109%, p = 0.06) and computer-calculated pain/paresthesia overlap (107%, p =
      0.17); higher scaled amplitude to cover the low back (106%, NS); and
      significantly lower voltage (78%, p = 0.0004), increased extraneous coverage
      (141%, p = 0.0000), and improved symmetry (25%, p = 0.001). Thus, we observed no
      significant technical advantage for the insulated 2 * 8 in treating axial low
      back pain.

PMID- 22151595
TI  - A Prospective, Open-label Study of Long-term Intrathecal Ziconotide for Chronic
      Nonmalignant Back Pain: A Case Report.
AB  - Ziconotide is an N-type calcium channel (NCC) blocking conopeptide, acting
      primarily at the NCC-rich dorsal horn. Reported here is an early experience with
      intrathecal ziconotide in a 55-year-old man with chronic pain resulting from
      failed back surgery. All conservative and surgical treatments, in addition to IT
      morphine, failed prior to enrollment in a short-term, placebo-controlled trial
      testing ziconotide efficacy and safety. Following successful short-term
      treatment, the patient was enrolled in a long-term follow-up study. The dosing
      regimen, onset and resolution of adverse events, and improvement on the primary
      efficacy measure, the Visual Analog Scale of Pain Intensity, are discussed.
      Overall, the patient responded positively to ziconotide.

PMID- 22151597
TI  - Sensitivity and specificity of radiography for detection of elbow incongruity in
      clinical patients.
AB  - Elbow incongruity is an important factor regarding the treatment and prognosis of
      elbow dysplasia. Our purpose was to determine the sensitivity and specificity for
      radiographic detection of elbow incongruity in clinical patients, to establish
      inter- and intraobserver variation for different parameters, and to evaluate the
      possibility of radiographic grading of incongruity. Standard radiographic
      projections were acquired from 29 incongruent and nine congruent elbows of dogs
      of various ages and breeds. Computed tomography (CT) was used to diagnose and
      grade the incongruity. All radiographs were evaluated by four observers for
      detection and grading of elbow incongruity. Sensitivity, specificity, inter- and
      intraobserver variability were calculated. The mean sensitivity for detection of
      incongruity was very good (88.8%) with a mean specificity of 91.7%. Correct
      grading of incongruity was difficult. The radioulnar step and the widening of the
      humeroulnar and humeroradial joint space were seen most frequently. Intraobserver
      and interobserver variability were fair to excellent (Kappa = 0.372-0.809),
      depending on the investigated parameters. Radiography is valuable to screen for
      elbow incongruity. In over 91% of the patients, a clear distinction could be made
      between a congruent and an incongruent joint grading was not possible.

PMID- 22151598
TI  - Genetic diversity of wild grapevine populations in Spain and their genetic
      relationships with cultivated grapevines.
AB  - The wild grapevine, Vitis vinifera L. ssp. sylvestris (Gmelin) Hegi, considered
      as the ancestor of the cultivated grapevine, is native from Eurasia. In Spain,
      natural populations of V. vinifera ssp. sylvestris can still be found along river
      banks. In this work, we have performed a wide search of wild grapevine
      populations in Spain and characterized the amount and distribution of their
      genetic diversity using 25 nuclear SSR loci. We have also analysed the possible
      coexistence in the natural habitat of wild grapevines with naturalized grapevine
      cultivars and rootstocks. In this way, phenotypic and genetic analyses identified
      19% of the collected samples as derived from cultivated genotypes, being either
      naturalized cultivars or hybrid genotypes derived from spontaneous crosses
      between wild and cultivated grapevines. The genetic diversity of wild grapevine
      populations was similar than that observed in the cultivated group. The molecular
      analysis showed that cultivated germplasm and wild germplasm are genetically
      divergent with low level of introgression. Using a model-based approach
      implemented in the software structure, we identified four genetic groups, with
      two of them fundamentally represented among cultivated genotypes and two among
      wild accessions. The analyses of genetic relationships between wild and
      cultivated grapevines could suggest a genetic contribution of wild accessions
      from Spain to current Western cultivars.

PMID- 22151599
TI  - Paradoxical worsening of spasticity and pain in the lower extremities after
      increasing the dose of intrathecal baclofen--case report.
AB  - OBJECTIVES:   Some patients with spasticity and pain in the extremities fail to
      respond to increases in the dose of intrathecally delivered baclofen. MATERIALS
      AND METHODS:   We report a 78-year-old man with severe spasticity and pain in the
      lumbar region and both lower extremities because of ossification of the posterior
      longitudinal ligament, spinal canal stenosis, and cerebral infarction. He was
      severely disabled and bedridden. Earlier surgical interventions (spinal cord
      stimulation and deep brain stimulation) had failed. RESULTS:   He underwent a
      screening test for intrathecal baclofen (ITB) therapy. The intrathecal injection
      of 50 ug baclofen severely aggravated his spasticity and pain and concomitantly
      elicited myoclonic-like involuntary movements in both lower extremities. Although
      25 ug baclofen produced similar results, overt improvements were obtained with
      12.5 ug, and he underwent implantation of an ITB pump. His spasticity and pain
      responded to initial daily doses of 12.5 ug. To obtain further improvements, we
      gradually increased the daily dose to 40 ug; however, this severely increased his
      spasticity and pain in both lower extremities and concomitantly elicited
      myoclonic-like involuntary movements. He is being maintained on a daily dose of
      20 ug/day. CONCLUSIONS:   We suggest that in patients who experience symptom
      aggravation at increased ITB doses, potential causative factors and ITB system
      malfunction should first be ruled out, and consideration should then be given to
      decreasing the ITB dose.

PMID- 22151601
TI  - Partial aneurysmectomy is effective in managing aneurysm-associated complications
      of arteriovenous fistulae for hemodialysis: case series and literature review.
AB  - Fistula aneurysms are commonly seen and usually do not affect fistula function
      for hemodialysis. However, these aneurysms are associated with complications that
      increase the risk of fistula bleeding and loss. The common feature of these
      complications is that the diseased tissues usually affect a localized area of an
      aneurysm. Accordingly, we developed a targeted intervention "partial
      aneurysmectomy" in which only the diseased area was resected. In this report, we
      sought to examine the outcomes of partial aneurysmectomies performed in 36 cases
      for the following indications: active bleeding (14%), skin scab plus fistula
      defect in imminent danger of bleeding (33%), skin necrosis and erosion (28%), and
      thin-walled aneurysm in danger of rupture (25%). Postoperatively, all patients
      continued hemodialysis using their fistulae. During 2-18-month follow-up, all
      fistulae but one were functional and required no intervention on the repaired
      areas. At 6 months, the aneurysm primary patency, fistula primary patency, and
      fistula-assisted primary patency rates were 97%, 56%, and 97%, respectively. In
      conclusion, partial aneurysmectomy is a simple and effective intervention for
      managing aneurysm-associated complications and preserving fistula function. Owing
      to its advantages over other interventions, we recommend partial aneurysmectomy
      as first-line choice for managing aneurysm-associated complications.

PMID- 22151600
TI  - Comparison of associations of adherence to a Dietary Approaches to Stop
      Hypertension (DASH)-style diet with risks of cardiovascular disease and venous
      thromboembolism.
AB  - BACKGROUND: Venous thromboembolism (VTE) and cardiovascular disease (CVD) share
      some risk factors, including obesity, but it is unclear how dietary patterns
      associated with reduced risk of CVD relate to risk of VTE. OBJECTIVE:  To compare
      the relationships of adherence to a Dietary Approaches to Stop Hypertension
      (DASH)-style diet with the risks of CVD and VTE. PATIENTS/METHODS: We confirmed
      by medical record review 1094 incident cases of CVD and 675 incident VTEs during
      a mean follow-up of 14.6 years in 34 827 initially healthy participants in the
      Women's Health Study who completed at baseline a 133-item food frequency
      questionnaire scored for adherence to a DASH diet. We compared estimated
      associations of dietary patterns with CVD and VTE from proportional hazards
      models in a competing risk framework. RESULTS: Initial analyses adjusted for age,
      energy intake and randomized treatments showed 36-41% reduced hazards of CVD
      among women in the top two quintiles of DASH score relative to those in the
      bottom quintile (P(trend) < 0.001). In multivariate analysis, women in the top
      two quintiles had 12-23% reduced hazards of CVD relative to women in the bottom
      quintile (P(trend) = 0.04). Analyses restricted to coronary events showed more
      variable 10-33% reduced hazards in the top two quintiles (P(trend) = 0.09). In
      contrast, higher DASH scores were unrelated to risk of VTE, with a 1% reduced
      hazard for the top vs. bottom quintile (P(trend) = 0.95). CONCLUSION: An
      apparently strong association of adherence to the DASH diet with incidence of CVD
      was attenuated upon control for confounding variables. Adherence to the DASH diet
      was not associated with risk of VTE in women.

PMID- 22151602
TI  - The evolution of the tape measure protein: units, duplications and losses.
AB  - BACKGROUND: A large family of viruses that infect bacteria, called phages, is
      characterized by long tails used to inject DNA into their victims' cells. The
      tape measure protein got its name because the length of the corresponding gene is
      proportional to the length of the phage's tail: a fact shown by actually copying
      or splicing out parts of DNA in exemplar species. A natural question is whether
      there exist units for these tape measures, and if different tape measures have
      different units and lengths. Such units would allow us to retrace the evolution
      of tape measure proteins using their duplication/loss history. The vast number of
      sequenced phages genomes allows us to attack this problem with a comparative
      genomics approach. RESULTS: Here we describe a subset of phages whose tape
      measure proteins contain variable numbers of an 11 amino acids sequence repeat,
      aligned with sequence similarity, structural properties, and simple arithmetics.
      This subset provides a unique opportunity for the combinatorial study of phage
      evolution, without the added uncertainties of multiple alignments, which are
      trivial in this case, or of protein functions, that are well established. We give
      a heuristic that reconstructs the duplication history of these sequences, using
      divergent strains to discriminate between mutations that occurred before and
      after speciation, or lineage divergence. The heuristic is based on an efficient
      algorithm that gives an exhaustive enumeration of all possible parsimonious
      reconstructions of the duplication/speciation history of a single nucleotide.
      Finally, we present a method that allows, when possible, to discriminate between
      duplication and loss events. CONCLUSIONS: Establishing the evolutionary history
      of viruses is difficult, in part due to extensive recombinations and gene
      transfers, and high mutation rates that often erase detectable similarity between
      homologous genes. In this paper, we introduce new tools to address this problem.

PMID- 22151603
TI  - A formula for determining the standard liver volume in children: a special
      reference for neonates and infants.
AB  - Accurately evaluating the ratio of GV to the SLV (GV/SLV) is important in
      successful pediatric liver transplantation. However, the formula used to
      calculate the SLV of children, including neonates and infants, has not yet been
      established. The aim of the current study was to estimate the SLV of children,
      including neonates, and to establish an accurate formula. The LV of 100 children
      (including 7 neonates and 15 infants) were measured using thin slice (3-5 mm)
      helical CT images. Their BSA was calculated from height and weight. A new formula
      to estimate the SLV was established as follows: SLV (mL) =689.9 * BSA (m(2)) 
      24.7. The SLV of children was significantly lower than that in previous reports
      (p < 0.001). A formula for calculating the SLV of children including neonates was
      established. This new formula will be useful in pediatric liver transplantation.

PMID- 22151604
TI  - SNPInterForest: a new method for detecting epistatic interactions.
AB  - BACKGROUND: Multiple genetic factors and their interactive effects are speculated
      to contribute to complex diseases. Detecting such genetic interactive effects,
      i.e., epistatic interactions, however, remains a significant challenge in large
      scale association studies. RESULTS: We have developed a new method, named
      SNPInterForest, for identifying epistatic interactions by extending an ensemble
      learning technique called random forest. Random forest is a predictive method
      that has been proposed for use in discovering single-nucleotide polymorphisms
      (SNPs), which are most predictive of the disease status in association studies.
      However, it is less sensitive to SNPs with little marginal effect. Furthermore,
      it does not natively exhibit information on interaction patterns of
      susceptibility SNPs. We extended the random forest framework to overcome the
      above limitations by means of (i) modifying the construction of the random forest
      and (ii) implementing a procedure for extracting interaction patterns from the
      constructed random forest. The performance of the proposed method was evaluated
      by simulated data under a wide spectrum of disease models. SNPInterForest
      performed very well in successfully identifying pure epistatic interactions with
      high precision and was still more than capable of concurrently identifying
      multiple interactions under the existence of genetic heterogeneity. It was also
      performed on real GWAS data of rheumatoid arthritis from the Wellcome Trust Case
      Control Consortium (WTCCC), and novel potential interactions were reported.
      CONCLUSIONS: SNPInterForest, offering an efficient means to detect epistatic
      interactions without statistical analyses, is promising for practical use as a
      way to reveal the epistatic interactions involved in common complex diseases.

PMID- 22151605
TI  - Influences of exercise and training on the circulating concentration of prolactin
      in humans.
AB  - Physical activity has an impact on several endocrine functions. During exercise,
      certain endocrine adjustments are required to maintain the homeostasis. It is
      well known that, depending on the intensity and duration, exercise stimulates the
      release of the hormone prolactin (PRL). After the cessation of acute exercise,
      this effect persist and continues during the recovery period. Chronic exercise
      can affect the PRL basal concentration and/or the PRL response to acute exercise.
      The main functions of PRL are associated with the maintenance of homeostasis and
      processes of reproduction. A role for PRL also has been recognised as an
      important regulator of cellular proliferation. The present review examines the
      exercise-induced acute or adaptive responses of PRL secretion. It is also
      hypothesised that increased concentrations of PRL during exercise could play an
      important role for neuroplasticity as a result of involvement of the hormone in
      the neurogenesis in subventricular zone of the adult brain.

PMID- 22151606
TI  - HdfR is a regulator in Photorhabdus luminescens that modulates metabolism and
      symbiosis with the nematode Heterorhabditis.
AB  - The bacterium, Photorhabdus luminescens, is an insect pathogen that also
      maintains a mutualistic interaction with nematodes from the family
      Heterorhabditis. Photorhabdus luminescens is carried in the gut of the infective
      juvenile (IJ), a nematode stage that infects soft-cuticled insect larvae in the
      soil. Photorhabdus luminescens is released into the insect blood to convert the
      insect into a biomass that is able to support nematode growth and development.
      Nematode reproduction continues for 2-3 generations before the nematodes enter an
      alternative developmental pathway leading to a new generation of IJs that are
      efficiently colonized by P. luminescens in a process called transmission.
      Transmission begins with the adherence of P. luminescens to the rectal gland
      cells (RGC) located in the gut of the hermaphrodite. The bacteria enter, and
      replicate within, the RGC resulting in vacuolization, and ultimately lysis, of
      the RGC. In this way P. luminescens are released throughout the body cavity of
      the hermaphrodite to encounter, and colonize, the developing IJs. In this study
      we show that the LysR-type regulator, HdfR, is required for normal transmission
      in P. luminescens TTO1. Transcriptome analysis revealed that HdfR regulates the
      expression of 124 genes, including genes involved in arginine metabolism,
      hydroxyphenylacetate catabolism and pigment production. Using fluorescence
      microscopy we show that the DeltahdfR mutant is able to attach to, and grow
      within, the hermaphrodite as well as wild-type bacteria but subsequent steps in
      transmission are delayed. Therefore, HdfR plays an important role in coordinating
      the interaction between P. luminescens and its nematode partner during
      transmission.

PMID- 22151607
TI  - MRI in patients with acute basilar artery occlusion - DWI lesion scoring is an
      independent predictor of outcome.
AB  - AIMS: We analyzed early diffusion-weighted magnetic resonance imaging of patients
      with acute basilar artery occlusion by applying different lesion scoring systems
      and determined their predictive value for favorable outcome. METHODS: Between
      1998 and 2010, patients with confirmed basilar artery occlusion were entered in a
      local database. magnetic resonance imaging angiography was performed for
      diagnosis of basilar artery occlusion and/or during initiated recanalization
      therapy. We analyzed the patients' clinical and radiological baseline data,
      recanalization, and favorable outcome modified Rankin Scale 0-2 after three
      months. Diffusion weighted imaging findings were categorized into lesions in
      vascular territories as well as by two previously published scores for ischemic
      damage in the posterior circulation, the Renard score and posterior circulation
      Acute Stroke Prognosis Early computed tomography Score. RESULTS: Fifty patients
      with basilar artery occlusion received an early MRI, and in 30 of those, a follow
      up MRI was performed. Median time to baseline MRI was 5.5 h (one-hour to 24 h).
      Median baseline Renard score and posterior circulation Acute Stroke Prognosis
      Early CT Score were 2.75 (0-10) and 7 (0-10), respectively. Of the patients, 82%
      received an acute recanalization therapy and in 78% of those, the basilar artery
      recanalized. Median time to therapy was five-hours (1.25-20 h). 24% of all
      patients had a favorable outcome (mRS 0-2). Patients with a favorable outcome had
      a lower Renard score and higher pcASPECTS, a lower rate of complete basilar
      artery occlusion, a higher Glasgow coma scale on admission, and a higher rate of
      successful recanalization (all P < 0.05). After logistic regression, the only
      independent predictor for favorable outcome was a posterior circulation Acute
      Stroke Prognosis Early CT Score of 8 or more points (odds ratio 3.9, 95%
      confidence interval 1.4-11.7, P < 0.05). CONCLUSION: In patients with acute
      basilar artery occlusion, posterior circulation Acute Stroke Prognosis Early CT
      Score of 8 or more points on early diffusion weighted imaging is an independent
      predictor for favorable outcome.

PMID- 22151608
TI  - Dynamics of cognitive change in HIV-infected individuals commencing three
      different initial antiretroviral regimens: a randomized, controlled study.
AB  - BACKGROUND: Improvements in neurocognitive (NC) function have been associated
      with commencing antiretroviral therapy in HIV-infected subjects. However, the
      dynamics of such improvements are poorly understood. METHODS: We assessed changes
      in NC function via a validated computerized battery (CogStateTM, Melbourne,
      Victoria, Australia) at baseline and after 24 and 48 weeks in a subset of therapy
      naive neuro-asymptomatic HIV-infected subjects, randomized to commence three
      different antiretroviral regimens. RESULTS: Of 28 subjects enrolled in the study,
      nine, eight and 11 were randomly allocated to commence tenofovir/emtricitabine
      with efavirenz (arm 1), atazanavir/ritonavir (arm 2) and zidovudine/abacavir (arm
      3), respectively. Overall improvements in NC function were observed at week 24
      and function continued to improve at week 48 (changes in z-score for overall
      cognitive global score of 0.16 and 0.18 at weeks 24 and 48, respectively). Within
      the NC speed domains, generally greater improvements were observed in arms 2 and
      3, compared with arm 1 (changes in z-score for composite speed scores at weeks
      24/48 of 0.16/0.16, -0.29/-0.24 and -0.15/-0.31 in arms 1, 2 and 3, respectively;
      P = 0.04 for change at week 48 in arm 3 versus arm 1). Finally, improvements in
      executive function occurred later (only observed at week 48) and were driven by
      improvements in arm 3 (z-score changes of 0.23, 0.06 and -0.78 in arms 1, 2 and
      3, respectively; P = 0.02 for change in arm 3 versus arm 1). CONCLUSION:
      Improvements in NC function continue over the first year after initiating
      antiretroviral therapy in neuro-asymptomatic HIV-infected subjects.

PMID- 22151610
TI  - Perineuromal stimulation in the treatment of occipital neuralgia: a case study.
AB  - This case study is presented to exemplify the application of a perineuromal
      approach in the treatment of recalcitrant occipital neuralgia. The patient was a
      49-year-old female with severe and disabling occipital neuralgia. The pain
      persisted despite several surgical procedures, injections in the affected area,
      and medications. Threading the electrode into the cervical epidural space and
      attempts at peripheral stimulation using the Weiner and Reed approach were
      unsuccessful. Immediate benefit was derived when the electrode was advanced
      subcutaneously and positioned underneath the neuroma apparently created by a C2
      nerve transection. A Medtronic Octad (model #3898) was utilized. The patient was
      contacted at seven and nine months post implantation. She reported 90%
      improvement in her pain. The improvements were also noted in numerical pain
      ratings, Beck Depression Inventory, and Oswestry Disability Scale. These
      improvements were corroborated by her husband. The Minnesota Multiphasic
      Personality Inventory (MMPI) remained relatively unchanged. This case illustrates
      the possible utilization of perineuromal stimulation in the treatment of
      occipital neuralgia. The specific mechanism of action remains unclear.
      Replication and controlled studies are required to determine the general
      applicability of this approach.

PMID- 22151611
TI  - Sacral nerve root stimulation for the treatment of urge incontinence and detrusor
      dysfunction utilizing a cephalocaudal intraspinal method of lead insertion: a
      case report.
AB  - Sacral nerve root stimulation (SNRS) is known to be effective in the treatment of
      pelvic motor dysfunction(1-4). Bladder and urethral motor disorders commonly
      treated include urinary urge incontinence, voiding/detrusor dysfunction, and
      urgency/frequency syndromes. To date, neurostimulation specific to bladder and
      urethral dysfunction has applied a unilateral, trans-sacral approach. (Interstim,
      Medtronic, Minneapolis, MN) Despite some success, this method has been associated
      with technical failures in maintaining electrode position(5,6). As an
      alternative, this case report describes the selective epidural application of a
      cephalocaudal ("retrograde") lead insertion method in a patient with severe
      detrusor dysfunction and urinary urge incontinence(7).

PMID- 22151609
TI  - Predictors of adherence to isoniazid preventive therapy among HIV positive adults
      in Addis Ababa, Ethiopia.
AB  - BACKGROUND: Isoniazide preventive therapy (IPT) is given to individuals with
      latent infection of tuberculosis (TB) to prevent the progression to active
      disease. One of the primary reasons for failure of IPT is poor adherence.
      METHODS: A cross sectional study was conducted in four hospitals in Addis Ababa.
      Data were collected using a pre-tested interviewer-administered structured
      questionnaire. Bivariate and multivariate analysis was done to identify
      predictors of IPT. RESULTS: A total of 319 (97.5%) individual participated in
      this study. Within seven days recall period, self-reported dose adherence rate
      was 86.5%. Individual who received explanation about IPT from health care
      providers (OR = 7.74; 95%CI: 3.144, 19.058); who had good feeling/comfortable to
      take IPT in front of other people [OR = 5.981, 95%CI (2.308, 15.502)] and who
      attended clinical appointment regularly (OR = 4.0; 95%CI: 1.062, 15.073) were
      more likely to adhere to IPT. Participants who developed IPT related adverse
      effect were 93% less likely to adhere to the prescribed doses (OR = 0.065; 95%CI:
      0.024, 0.179). CONCLUSION: The prevalence of self reported dose adherence over
      the past 7 days was higher. Non-adherence was observed among respondent who were
      not provided with sufficient information about IPT. The health care providers
      need to strengthen their educational and counseling efforts to convince the
      patient before putting them on IPT. To enhance adherence, health education
      efforts should focus on the importance of IPT, the details of the regimen and
      adverse effects.

PMID- 22151612
TI  - Epidural spinal cord stimulation with a multiple electrode paddle lead is
      effective in treating intractable low back pain.
AB  - The objective of this paper is to examine the outcomes of patients with
      intractable low-back pain treated with epidural spinal cord stimulation (SCS)
      utilizing paddle electrodes and a radio frequency (RF) stimulator. A multicenter
      prospective study was performed to collect data from patients suffering from
      chronic low-back pain. The study was designed to collect data from 60 patients at
      four centers and examine their outcomes at, or up to two years post implantation.
      Patients' participation included written responses to a series of preoperative
      questionnaires that were designed to collect previous surgical history
      information, leg and low back pain characteristics, and routine demographic
      information. Outcome measurements included the visual analog scale (VAS), the
      Oswestry Disability Questionnaire, the Sickness Impact Profile (SIP), and a
      patient satisfaction rating scale. Data were collected at each site during
      patient visits or by mail, at approximately six months, 12 months, and 24 months.
      A total of 44 patients have been implanted with a SCS system at the time of this
      writing. Follow-up data were available for 41 patients. Preoperatively, all
      patients reported more than 50% of their pain in the low back. All patients had
      pain in both their backs and legs. All patients showed a reported mean decrease
      in their 10-point VAS scores compared to baseline. The majority of patients
      reported fair to excellent pain relief in both the low back and legs. At six
      months 91.6% of the patients reported fair to excellent relief in the legs and
      82.7% of the patients reported fair to excellent relief in the low back. At one
      year 88.2% of the patients reported fair to excellent relief in the legs and
      68.8% of the patients reported fair to excellent relief in the low back.
      Significant improvement in function and quality of life was found at both the six
      month and one-year follow-ups using the Oswestry and SIP, respectively. The
      majority of patients reported that the procedure was worthwhile (92% at six
      months, 88% at one year). No patient indicated that the procedure was not
      worthwhile. We conclude that SCS proved beneficial at one year for the treatment
      of patients with chronic low back and leg pain.

PMID- 22151613
TI  - An interesting and heretofore unreported infection of a spinal cord stimulator:
      smitten by a kitten revisited.

PMID- 22151614
TI  - Letter to the editor.

PMID- 22151615
TI  - Reply to a letter to the editor (2001;4:35-36).

PMID- 22151616
TI  - Does the drop-foot stimulator improve walking in hemiplegia?
AB  - This article presents an overview of the research and clinical experience of the
      use of Functional Electrical Stimulation (FES) for the treatment of drop-foot in
      hemiplegia. The article reviews the evidence from the literature over the past 10
      years to answer the question posed in the title. A description and explanation of
      drop-foot stimulation is followed by a review and discussion of the literature
      based on a search of the databases Medline, Cinhal, and Embase from 1990 to 2000,
      using the key words: stimulation and hemiplegia and (common and peroneal) or
      (functional and electrical) and (walking or gait) and drop* foot). Nine papers
      were reviewed, only one of which was a randomized controlled trial. Quality of
      research is criticized and the need for rigorous clinical studies, technological
      development, and collaboration between clinicians and engineers is argued. The
      drop foot stimulator does improve walking in hemiplegia, but factors such as
      patient and clinician education, reliability of equipment, and selection of
      patients, are important.

PMID- 22151617
TI  - Electrical stimulation for modulation of spasticity in hemiplegic and spinal cord
      injury subjects.

PMID- 22151618
TI  - HIF-1alpha and HSP90: target molecules selected from a tumorigenic papillary
      thyroid carcinoma cell line.
AB  - It is important to properly identify aggressive tumors among differentiated
      thyroid cancers that are most often indolent. By comparison of a tumorigenic
      clone with an originally less tumorigenic papillary thyroid carcinoma (PTC) cell
      line, we looked for markers involved in the aggressive biology of thyroid cancer.
      Human PTC cell lines BHP10-3 and its tumorigenic subclone BHP10-3SC(mice) were
      compared using microarray analysis. Upregulated genes in the tumorigenic clone
      were selected for RT-PCR, immunoblot analysis and immunohistochemistry in human
      tissue. Hypoxia-inducible factor (HIF)-1alpha and its chaperone protein heat
      shock protein (HSP)90 showed significantly increased expression in BHP10
      3SC(mice) and human PTC tissue. These two genes, HIF-1alpha and HSP90, were
      further validated using siRNA gene knockdown, pharmacological inhibition using 17
      N-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of both HSP90 and
      HIF-1alpha and in vivo orthotopic animal model. Invasiveness of BHP10-3SC(mice)
      was abrogated by blockade of HIF-1alphain vitro by both siRNA and 17-AAG. The
      same finding was demonstrated in the orthotopic animal model. These findings
      support that HIF-1alpha is important in tumorigenesis of PTC and that it may
      serve to be an important target for identification and treatment of aggressive
      tumors.

PMID- 22151619
TI  - Topical morphine gel in the treatment of painful leg ulcers, a double-blind,
      placebo-controlled clinical trial: a pilot study.
AB  - Chronic painful wounds, a major health problem, have a detrimental impact on the
      quality of life due to associated pain. Some clinical reports have suggested that
      local administration of morphine could be beneficial. The aim of this study was
      to evaluate the analgesic effect of topically applied morphine on chronic painful
      leg ulcers. Twenty-one patients were randomly assigned to receive either morphine
      or placebo in a randomised, placebo-controlled, crossover pilot study. Each
      patient was treated four times in total. Pain was measured by the visual analogue
      score (VAS) before application of gel, directly after and after 2, 6, 12 and 24
      hours. Although an overall, clinically relevant, reduction of pain was observed
      upon treatment with morphine, the difference was not statistically significant.
      Morphine reduced pain scores more than placebo on treatment occasions 1 and 2.
      The difference was statistically significant only 2 hours after dressing on the
      first treatment occasion. Thus, our study did not demonstrate a consistent and
      globally significant difference in nociception in patients treated with morphine.
      However, the relatively small number of patients included in our study and other
      methodological limitations makes it difficult for us to draw general conclusions
      regarding efficacy of topically applied morphine as an effective treatment for
      some painful ulcers. Further studies are warranted to evaluate the value of
      topically applied morphine in the treatment of patients with chronic painful leg
      ulcers.

PMID- 22151620
TI  - Age- and region-specific hepatitis B prevalence in Turkey estimated using
      generalized linear mixed models: a systematic review.
AB  - BACKGROUND: To provide a clear picture of the current hepatitis B situation, the
      authors performed a systematic review to estimate the age- and region-specific
      prevalence of chronic hepatitis B (CHB) in Turkey. METHODS: A total of 339
      studies with original data on the prevalence of hepatitis B surface antigen
      (HBsAg) in Turkey and published between 1999 and 2009 were identified through a
      search of electronic databases, by reviewing citations, and by writing to
      authors. After a critical assessment, the authors included 129 studies, divided
      into categories: 'age-specific'; 'region-specific'; and 'specific population
      group'. To account for the differences among the studies, a generalized linear
      mixed model was used to estimate the overall prevalence across all age groups and
      regions. For specific population groups, the authors calculated the weighted mean
      prevalence. RESULTS: The estimated overall population prevalence was 4.57, 95%
      confidence interval (CI): 3.58, 5.76, and the estimated total number of CHB cases
      was about 3.3 million. The outcomes of the age-specific groups varied from 2.84,
      (95% CI: 2.60, 3.10) for the 0-14-year olds to 6.36 (95% CI: 5.83, 6.90) in the
      25-34-year-old group. CONCLUSION: There are large age-group and regional
      differences in CHB prevalence in Turkey, where CHB remains a serious health
      problem.

PMID- 22151621
TI  - Impact of dietary vitamin D on osseointegration in the ovariectomized rat.
AB  - AIM: Vitamin D deficiency is highly prevalent in the population and associated
      with impaired peri-implant bone regeneration. Yet, there is a gap in
      understanding the impact of vitamin D supplementation on the process of
      osseointegration. In this study, the effect of vitamin D supplementation on peri
      implant bone regeneration was investigated. METHODS: Fifty ovariectomized Sprague
      Dawley rats were divided into three groups. The depletion group was fed a vitamin
      D-free diet for 8 weeks. The repletion group received vitamin D-free diet for 6
      weeks, before animals were switched to standard diet containing 2400 IU/kg
      vitamin D. The control group was fed the standard diet. Two titanium mini
      implants were placed in the tibia. All groups remained on their previous diet
      until sacrifice. Blood sample testing and histomorphometric analysis were
      performed. RESULTS: Vitamin D depletion caused a significant reduction in 25
      hydroxvitamin D in rat serum that returned to control levels in the repletion
      group. This vitamin deficiency was associated with a decrease in bone-to-implant
      contact in the cortical area, which was leveled to controls in the repletion
      group. No significant changes by vitamin D depletion were noticed in the medullar
      compartment. Moreover, also the peri-implant bone area and the mineral apposition
      rate remained unchanged upon vitamin D depletion. CONCLUSION: These results
      indicate that vitamin D deficiency has a negative impact on cortical peri-implant
      bone formation in ovariectomized rats, which can be compensated by vitamin D
      supplementation. This study provides first insight into the potential beneficial
      effect of vitamin D supplementation in implant dentistry.

PMID- 22151623
TI  - Personality disorders and psychosocial problems in a group of participants to
      therapeutic processes for people with severe social disabilities.
AB  - BACKGROUND: Homeless people have high dropout rates when they participate in
      therapeutic processes. The causes of this failure are not always known. This
      study investigates whether dropping-out is mediated by personality disorders or
      whether psychosocial problems are more important. METHOD: Eighty-nine homeless
      people in a socio-laboral integration process were assessed. An initial interview
      was used, and the MCMI II questionnaire was applied to investigate the presence
      of psychosocial disorders (DSM-IV-TR axis IV). This was designed as an ex post
      facto prospective study. RESULTS: Personality disorders were very frequent among
      the homeless people examined. Moreover, the high index of psychosocial problems
      (axis IV) in this population supported the proposal that axis IV disorders are
      influential in failure to complete therapy. CONCLUSION: The outcomes of the study
      show that the homeless people examined presented with more psychopathological
      symptoms, in both axis II and axis IV, than the general population. This supports
      the need to take into account the comorbidity between these two types of disorder
      among homeless people, in treatment and in the development of specific
      intervention programs. In conclusion, the need for more psychosocial treatments
      addressing the individual problems of homeless people is supported.

PMID- 22151624
TI  - Patients' attitudes towards patient involvement in safety interventions: results
      of two exploratory studies.
AB  - BACKGROUND: In recent years, patient-focused interventions have been introduced
      aimed at increasing patient involvement in safety-related behaviours. However,
      patients' attitudes towards these interventions and comfort in participating in
      the recommended behaviours remain largely unexplored. OBJECTIVE: To evaluate
      patients' attitudes towards a video and leaflet aimed at encouraging patient
      involvement in safety-related behaviours. DESIGN: Two exploratory studies
      employing a within-subjects mixed-methods design. SETTING: Six hospital wards on
      an inner-city London teaching hospital. PARTICIPANTS: Medical and surgical
      inpatients: 80 patients in study 1 (mean age 55; 69% men) and 80 patients in
      study 2 (mean age 52; 60% men). INTERVENTION: Patients watched the PINK patient
      safety video (study 1) or read the National Patient Safety Agency's 'Please Ask'
      about staying in hospital leaflet (study 2). MAIN OUTCOME MEASURES: Perceived
      comfort in participating in safety-related behaviours; attitudes towards the
      video or leaflet. RESULTS: Both video and leaflet increased patients' perceived
      comfort in engaging in some (but not all) safety-related behaviours (P < 0.05).
      In both studies, the majority of patients questioned whether the intervention
      could help to reduce medical errors in health care. Suggestions on how the
      video/leaflet could be improved mainly related to content and layout. CONCLUSION:
      Video and leaflet could be effective at encouraging patient involvement in some
      safety-related behaviours. Further in-depth research on patients' attitudes
      towards different educational materials is required to help inform future
      policies and interventions in this very important but under-researched area.

PMID- 22151626
TI  - A method to maintain the thickness of the mouthguard after the vacuum forming
      process: changes of the holding conditions of the mouthguard sheet.
AB  - The aim of this study was to investigate differences in the thickness of the
      mouthguard sheet according to the holding conditions during heating. The material
      used in this study was Sports Mouthguard (3.8 mm thickness), and two holding
      conditions of the sheet were undertaken: one was the condition that the sheet was
      held all around the periphery and the other was that the sheet was held at only
      four points. The sheets were formed using a vacuum former when the sheets were
      heated until they hung 2.0 cm from the baseline. We measured the thickness of
      each part of the mouthguard and calculated the ratio of changes in the thickness.
      The difference in the thickness by the holding conditions at the area of the
      sheet that fitted over the anterior teeth, palate, and posterior teeth was
      analyzed by the paired t-test. The results showed that the thickness of the sheet
      differed statistically and significantly at the regions of the sheet that fitted
      over the anterior teeth and posterior teeth (P < 0.01) and the palate (P < 0.05)
      according to the holding conditions of the sheet. The thickness of the condition
      that the sheet was held all around the periphery was thinner than that of the
      condition that the sheet was held at only four points. These results suggested
      that the thickness of the sheet was maintained by holding the sheet only at four
      points, and this new method could be an effective way to maintain the thickness
      of the mouthguard in clinical use.

PMID- 22151627
TI  - Vision impairment during cardiac surgery and extracorporeal circulation: current
      understanding and the need for further investigation.
AB  - The aim of this article was to provide a comprehensive review of current
      knowledge regarding ocular hemodynamic alterations affecting the retinal
      neuroglial cells and optic nerve head (ONH) function during cardiac surgery.
      Literature indicates that visual loss after heart surgery is a rare but
      devastating complication provoked by two main causes of optic ischaemia and
      infarction during on-pump cardiac procedures: microembolism and/or hypoperfusion.
      Retinal ischaemia and ischaemic optic neuropathy are two possible major
      consequences of extracorporeal circulation in cardiac surgery. The hemodynamic
      modifications within the vascular beds of retina and ONH during cardiovascular
      operations have been incompletely studied. Consequently, it is of great interest
      to investigate the hemodynamic changes during cardiopulmonary bypass within the
      choroidal, retinal and optic nerve microcirculations as well as other potential
      causes of vaso-occlusion. Maintaining stable hemodynamic parameters during
      cardiovascular surgery seems to be the key to prevent visual impairment.

PMID- 22151625
TI  - Twelve-Step attendance trajectories over 7 years among adolescents entering
      substance use treatment in an integrated health plan.
AB  - AIMS: This study examines 12-Step attendance trajectories over 7 years, factors
      associated with the trajectories, and relationships between the trajectories and
      long-term substance use outcomes among adolescents entering out-patient substance
      use treatment in a private, non-profit integrated managed-care health plan.
      DESIGN: Longitudinal observational study. SETTING: Four Kaiser Permanente
      Northern California substance use treatment programs. PARTICIPANTS: A total of
      391 adolescents entering treatment between 2000 and 2002 who completed at least
      one follow-up interview in year 1, and at least one during years 3-7, after
      treatment entry. MEASUREMENTS: Alcohol and drug use, 12-Step meeting attendance
      and activity involvement and post-treatment medical service utilization.
      FINDINGS: Semiparametric group-based modeling identified three distinct 12-Step
      attendance trajectory groups over 7 years: low/no attendance (60%), early but not
      continued (26%) and continued (14%). There were lower proportions of males and of
      adolescents with prior substance use treatment experience in the low/no
      attendance group (P = 0.019 and P = 0.003, respectively). In addition, those in
      the low/no attendance group had lower perception on circumstances, motivation and
      readiness for treatment at baseline (P = 0.023). Multivariate logistic
      generalized estimating equation analyses found that those in the continued group
      were more likely to be abstinent from both alcohol and drugs during follow-ups
      than those in the low/no attendance group [odds ratio (OR) = 2.40, P = 0.003 and
      OR = 1.96, P = 0.026, respectively]. However, no differences in long-term
      outcomes were found between those in the other two groups. CONCLUSION: Robust
      connection with 12-Step groups appears to be associated with better long-term
      outcomes among adolescents with substance use disorders.

PMID- 22151629
TI  - The new investigator best manuscripts award.

PMID- 22151630
TI  - Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a
      randomized, double-blind, placebo-controlled clinical trial.
AB  - Objective.  The safety and efficacy of intrathecal (IT) ziconotide was studied in
      a randomized, double-blind, placebo-controlled trial. Materials and Methods. 
      Patients (169 ziconotide, 86 placebo) with severe chronic nonmalignant pain
      unresponsive to conventional therapy and a visual analog scale of pain intensity
      (VASPI score) >= 50 mm were treated over a 6-day period in an inpatient hospital
      setting. Initial starting dose was 0.4 ug/hour and was titrated to analgesia or
      intolerance (maximum dose 7.0 ug/hour). The starting and maximum doses were
      reduced to 0.1 ug/hour and 2.4 ug/hour, respectively, due to adverse events
      (AEs). Results.  The mean percent reduction in VASPI score from baseline was
      31.2% and 6.0% for ziconotide- and placebo-treated patients, respectively (p <=
      0.001). During the initial titration phase, a significantly greater percentage of
      patients in the ziconotide group compared to the placebo group reported AEs,
      including abnormal gait, amblyopia, dizziness, nausea, nystagmus, pain, urinary
      retention, and vomiting. Conclusion.  Ziconotide provided significant analgesia
      in patients for whom conventional therapy failed. However, there was a
      considerable incidence of ziconotide-associated AEs due to the rapid titration
      and high doses administered.

PMID- 22151628
TI  - Are prescribing doctors sensitive to the price that their patients have to pay in
      the Spanish National Health System?
AB  - BACKGROUND: This study aims to design an empirical test on the sensitivity of the
      prescribing doctors to the price afforded for the patient, and to apply it to the
      population data of primary care dispensations for cardiovascular disease and
      mental illness in the Spanish National Health System (NHS). Implications for drug
      policies are discussed. METHODS: We used population data of 17 therapeutic groups
      of cardiovascular and mental illness drugs aggregated by health areas to obtain
      1424 observations ((8 cardiovascular groups * 70 areas) + (9 psychotropics groups
      * 96 areas)). All drugs are free for pensioners. For non-pensioner patients 10 of
      the 17 therapeutic groups have a reduced copayment (RC) status of only 10% of the
      price with a ceiling of ?2.64 per pack, while the remaining 7 groups have a full
      copayment (FC) rate of 40%. Differences in the average price among dispensations
      for pensioners and non-pensioners were modelled with multilevel regression models
      to test the following hypothesis: 1) in FC drugs there is a significant positive
      difference between the average prices of drugs prescribed to pensioners and non
      pensioners; 2) in RC drugs there is no significant price differential between
      pensioner and non-pensioner patients; 3) the price differential of FC drugs
      prescribed to pensioners and non-pensioners is greater the higher the price of
      the drugs. RESULTS: The average monthly price of dispensations to pensioners and
      non-pensioners does not differ for RC drugs, but for FC drugs pensioners get more
      expensive dispensations than non-pensioners (estimated difference of ?9.74 by DDD
      and month). There is a positive and significant effect of the drug price on the
      differential price between pensioners and non-pensioners. For FC drugs, each
      additional euro of the drug price increases the differential by nearly half a
      euro (0.492). We did not find any significant differences in the intensity of the
      price effect among FC therapeutic groups. CONCLUSIONS: Doctors working in the
      Spanish NHS seem to be sensitive to the price that can be afforded by patients
      when they fill in prescriptions, although alternative hypothesis could also
      explain the results found.

PMID- 22151631
TI  - Cautious Use of Intrathecal Baclofen in Walking Spastic Patients: Results on Long
      term Follow-up.
AB  - Intrathecal baclofen is presently the most effective treatment for diffuse
      spasticity whatever the cause. The fact that both spasticity is always
      accompanied by a degree of muscle weakness and that any antispastic treatment
      causes a decrease in muscle strength indicate that major attention must be paid
      in treating spasticity in ambulant patients. Methods.  We present here a
      retrospective study, approved by the insitutional ethics committee, of 22
      ambulant spastic patients, selected as homogeneous for disease and disease
      duration, who were treated with intrathecal baclofen at the Istituto Nazionale
      Neurologico "C.Besta" in Milan. These patients were followed-up for to 15 years
      of treatment and their clinical assessment was enriched by the evaluation of
      their functional independence measurement (FIM) before and during treatment.
      Results.  There was improvement in quality of life as measured by the FIM scale;
      however, an increase in the patient's motor performance could not be detected.
      Conclusion.  Although we did not show any improvement in muscle performance,
      intrathecal baclofen did improve daily quality of life, even in spastic patients
      who were able to walk.

PMID- 22151632
TI  - Intramedullary placement of intrathecal catheter. Report of a rare complication
      of intrathecal therapy.
AB  - A rare complication of intrathecal drug therapy-inadvertent insertion of the
      intrathecal catheter into the matter of the spinal cord-is presented. The patient
      developed signs of progressive monoparesis immediately after implantation of an
      intrathecal drug delivery system. The underlying problem was diagnosed with
      computed tomographic (CT) myelography and magnetic resonance imaging. The
      symptoms resolved after the catheter was removed. The article discusses probable
      mechanism of the complication and possible ways of its prevention. The usefulness
      of CT myelography in determining the intrathecal catheter position relative to
      the spinal cord is emphasized.

PMID- 22151633
TI  - Deep brain stimulation for neuropathic pain.
AB  - Objectives.  To determine whether deep brain stimulation is an effective
      treatment for neuropathic pain of varied etiology. Material and Methods.  Thirty
      four patients with intractable neuropathic pain were prospectively studied using
      visual analog scores, McGill Pain Questionnaire, and Quality of Life
      Questionnaires (EUROQOL EQ-5D VAS, and SF-36 v-2). Patients had either deep brain
      stimulation of either the periventricular gray or ventroposterolateral nucleus of
      the thalamus, or both. Results.  Seventy-six percent of patients underwent
      permanent implantation. Overall reduction of pain intensity was 54%. The burning
      component of pain improved by 77%. Health-related quality of life improved by
      38%. Conclusions.  Deep brain stimulation is an effective treatment for
      neuropathic pain. The factors that influence outcome, including etiology and site
      of stimulation, are discussed.

PMID- 22151634
TI  - Psychiatric symptoms and subthalamic nucleus stimulation in Parkinson's disease.
      A retrospective study in our Japanese patients.
AB  - Objectives.  With respect to postoperative activities of daily living (ADL), we
      retrospectively investigated associated psychiatric symptoms that influenced
      beneficial effects of subthalamic nucleus (STN) stimulation in our Japanese
      patients with Parkinson disease (PD). Materials and Methods.  Twenty-five
      patients underwent bilateral STN stimulation. Pre- and 3 months after the
      surgery, their parkinsonian symptoms were evaluated with Unified Parkinson
      Disease Rating Scale (UPDRS) and Schwab-England (S-E) ADL scale. Stepwise
      multiple analysis was performed to determine the factors affecting postoperative
      ADL. Results.  Eleven out of 25 patients manifested drug-induced psychosis
      preoperatively, although their mean dosage of levodopa was small (366.4 +/- 152.7
      mg). Disease duration positively affected the severity of the patients'
      psychiatric symptoms. Postoperative S-E score showed a significant improvement
      compared to the pretreatment baseline in both of "on" and "off" medication
      states, as all their cardinal motor symptoms were significantly ameliorated.
      Preoperative scores for thought disorder and axial disability negatively impact
      on the postoperative S-E score in "on" state (p < 0.01). Preoperative score for
      intellectual impairment was only a significant predictor of worse postoperative
      ADL in "off" state. Conclusions.  The markedly lower dose of levodopa may suggest
      ethnic characteristics of our Japanese patients with respect to tolerance for
      antiparkinsonian medications. Preoperative manifestation of drug-induced
      psychosis and cognitive dysfunction were the major factor that strikingly
      suppressed daily activities after STN stimulation.

PMID- 22151635
TI  - Neurophysiologic intervention in deep brain stimulation treatment for movement
      disorders: a practical framework.
AB  - Clinical neurophysiology has always played an important interventional role
      throughout the perioperative stages in functional neurosurgery. On the one hand,
      some neurophysiologic procedures have become an integrated part of neurosurgery.
      On the other hand, in deep brain stimulation, although the surgical electrode
      implantation is an essential step, the therapeutic effects are actually produced
      by electrically modulating the physiologic activity of the brain. We review the
      topic of neurophysiologic intervention in the deep brain stimulation for movement
      disorders by presenting the evidence derived from our own experiences based on an
      integrated group located at two hospitals in London and Oxford, UK, and mainly
      covering tremor caused by multiple sclerosis, Parkinson's disease and dystonia.

PMID- 22151636
TI  - Personality: predictor of neurostimulation outcomes in patients with chest pain
      and normal coronary arteries.
AB  - Objectives.  To study the impact of personality traits on the effect of
      neurostimulation in patients with chest pain and normal coronary arteries.
      Materials and Methods.  Using the Dutch personality questionnaire, we
      retrospectively studied the personality traits in 33 patients treated with
      neurostimulation, either transcutaneous electrical nerve stimulation or spinal
      cord stimulation after 5 years. Neurostimulation was successful in 21 patients.
      Baseline characteristics and medication also were assessed for possible
      interactions with personality traits and neurostimulation outcome. Results. 
      Patients with beneficial neurostimulation scored lower on the "social inadequacy"
      scale than patients with neurostimulation failure (p = 0.032). In univariate
      analyses, low scores at the "social inadequacy" scale and the use of calcium
      antagonists were associated with beneficial outcome of neurostimulation. In
      multivariate analysis low scores at the "social inadequacy" scale remained an
      independent predictor for beneficial neurostimulation outcome, when adjusted for
      other variables. Conclusion.  Personality traits are a determining factor in the
      evaluation of neurostimulation for patients with chest pain and normal coronary
      arteries.

PMID- 22151637
TI  - Factors affecting impedance of percutaneous leads in spinal cord stimulation.
AB  - Objectives.  Although the load impedance of a pulse generator has a significant
      effect on battery life, the electrical impedance of contact arrays in spinal cord
      stimulation (SCS) has not been extensively studied. We sought to characterize the
      typical impedance values measured from common quadripolar percutaneous SCS
      contact arrays. Methods.  In 36 patients undergoing percutaneous trial
      stimulation for various chronic pain conditions, bipolar impedance between
      adjacent contacts of 64 leads with 9 mm center-to-center spacing was measured in
      two different vertebral level regions, cervical (C3-C7) and lower-thoracic (T7
      T12). Multiple linear regression was applied to analyze the contribution of six
      variables to the biological tissue portion of the impedance (excluding the
      resistance of the lead wires). Results.  The median impedance in the cervical
      region (351 +/- 90 Omega) was significantly lower (36%, p < 0.001) than in the
      lower-thoracic region (547 +/- 151 Omega). In addition, time since implant had a
      weaker but still significant effect on tissue impedance. Conclusions.  Results
      from finite-difference mathematical modeling of SCS suggest that the difference
      in tissue impedance related to vertebral level may be due to the dorsoventral
      position of the lead in the epidural space. The presence of a larger space
      between the triangularly shaped dorsal part of the vertebral arch and the round
      shape of the dural sac in the lower-thoracic region increases the likelihood that
      the stimulating lead will not make dural contact, and thus "see" an increased
      impedance from the surrounding epidural fat. This implies that the energy
      requirements for stimulation in the thoracic region will be higher than in the
      cervical region, at least during the acute phase of implant.

PMID- 22151638
TI  - Transcutaneous electrical nerve stimulation as prehospital emergency
      interventional care: treating acute pelvic pain in young women.
AB  - Objectives.  In Europe, patients with acute pelvic pain are transported to the
      hospital in an ambulance without an emergency physician. We hypothesized that
      transcutaneous electrical nerve stimulation (TENS) would be an effective
      noninvasive procedure for pain treatment. Methods.  We conducted a prospective,
      randomized, blinded study where 100 women were randomly assigned into a real- or
      a sham-TENS group. TENS began before the transport to the ambulance and was left
      in place until the arrival at the hospital. Each patient rated her pain on paper
      using a visual analog scale. Results.  Compared to sham TENS, patients with
      active TENS felt that their pain was reduced by half after treatment (p < 0.01),
      anxiety scores significantly decreased (p < 0.01), heart rate and arteriolar
      vasoconstriction decreased significantly (p < 0.01), and nausea (p < 0.01) was
      lessened. Overall satisfaction with the received care was significantly higher (p
      < 0.01). Conclusion.  TENS is a safe, rapid, and effective analgesic treatment
      for acute pelvic pain.

PMID- 22151639
TI  - Neuromodulation in epilepsy and in chronic pain: third meeting of the benelux
      neuromodulation society chapter of the international neuromodulation society
      november 18-19, 2004, ghent, belgium.

PMID- 22151640
TI  - Proceedings from the 2005 neuromodulation society of the United kingdom and
      ireland meeting.

PMID- 22151641
TI  - Implant-Driven Tibial Nerve Stimulation in the Treatment of Refractory Overactive
      Bladder Syndrome: 12-Month Follow-up.
AB  - Objectives.  To investigate feasibility and safety of implant-driven tibial nerve
      stimulation. Materials and Methods.  Eight patients with refractory overactive
      bladder were successfully treated with implanted percutaneous tibial nerve
      stimulation (PTNS). Patients were evaluated with bladder diaries, quality of life
      questionnaires, and physical examination before implantation, and at 3, 6, and 12
      months of follow-up. The primary objective was >= 50% reduction of the number of
      incontinence episodes and/or voids on bladder diary. The Wilcoxon signed ranks
      test was used. Results.  At 3, 6 and 12 months, respectively five, six, and four
      patients met the primary objective. At 3- and 6-month follow-up, voiding and
      quality of life parameters had significantly (p < 0.05) improved. Urinary tract
      infection, temporarily walking difficulties, and spontaneous radiating sensations
      were reported as adverse events and no local infection, erosion, or dislocation.
      Conclusions.  Implant-driven tibial nerve stimulation seems to be feasible and
      safe.

PMID- 22151642
TI  - Penetration depths of an infiltrant into proximal caries lesions in primary
      molars after different application times in vitro.
AB  - BACKGROUND: Caries infiltration aims to inhibit lesion progression, by occluding
      the porosities within the lesion body with low-viscosity resins. The ability in
      hampering lesion progression is correlated with the penetration depth (PD) of the
      infiltrant. AIM: This study aimed to compare the infiltration depths into
      proximal lesions in primary molars after different application times. DESIGN:
      Noncavitated natural caries lesions (n = 83) were etched with 15% HCl for 2 min
      and infiltrated for 0.5, 1, 3, or 5 min. Specimens were sectioned and PD at the
      maximum lesion depth (LD(max)) were analysed using dual fluorescence confocal
      microscopy. RESULTS: Percentage penetrations (PD/LD(max)) were significantly
      higher after 3 or 5 min compared with 0.5-min application (P < 0.05; Mann-Whitney
      test). For LD(max) <400 MUm, no significant differences were observed between
      application times (P > 0.05). For LD(max) >=400 MUm, 3- and 5-min application
      resulted in significantly deeper infiltration compared with 0.5 min (P < 0.05).
      After 1-min application, PD was significantly lower than 5 min (P < 0.05),
      PD/LD(max) did not differ from all other groups (P > 0.05). CONCLUSIONS: Natural
      noncavitated proximal lesions in primary molars were deeply infiltrated after 1
      min application in vitro. For deeper lesions, however, more consistent results
      were obtained after 3 min.

PMID- 22151643
TI  - The European influence on workers' compensation reform in the United States.
AB  - Workers' compensation law in the United States is derived from European models of
      social insurance introduced in Germany and in England. These two concepts of
      workers' compensation are found today in the federal and state workers'
      compensation programs in the United States. All reform proposals in the United
      States are influenced by the European experience with workers' compensation. In
      2006, a reform proposal termed the Public Health Model was made that would
      abolish the workers' compensation system, and in its place adopt a national
      disability insurance system for all injuries and illnesses. In the public health
      model, health and safety professionals would work primarily in public health
      agencies. The public health model eliminates the physician from any role other
      than that of privately consulting with the patient and offering advice solely to
      the patient. The Public Health Model is strongly influenced by the European
      success with physician consultation with industry and labor.

PMID- 22151644
TI  - Bee venom induces apoptosis through intracellular Ca2+ -modulated intrinsic death
      pathway in human bladder cancer cells.
AB  - OBJECTIVES: To focus on bee venom-induced apoptosis in human bladder cancer TSGH
      8301 cells and to investigate its signaling pathway to ascertain whether
      intracellular calcium iron (Ca(2+)) is involved in this effect. METHODS: Bee
      venom-induced cytotoxic effects, productions of reactive oxygen species and
      Ca(2+) and the level of mitochondrial membrane potential (DeltaPsim) were
      analyzed by flow cytometry. Apoptosis-associated proteins were examined by
      Western blot analysis and confocal laser microscopy. RESULTS: Bee venom-induced
      cell morphological changes and decreased cell viability through the induction of
      apoptosis in TSGH-8301 cell were found. Bee venom promoted the protein levels of
      Bax, caspase-9, caspase-3 and endonuclease G. The enhancements of endoplasmic
      reticulum stress-related protein levels were shown in bee venom-provoked
      apoptosis of TSGH-8301 cells. Bee venom promoted the activities of caspase-3,
      caspase-8, and caspase-9, increased Ca(2+) release and decreased the level of
      DeltaPsim. Co-localization of immunofluorescence analysis showed the releases of
      endonuclease G and apoptosis-inducing factor trafficking to nuclei for bee venom
      mediated apoptosis. The images revealed evidence of nuclear condensation and
      formation of apoptotic bodies by 4',6-diamidino-2-phenylindole staining and DNA
      gel electrophoresis showed the DNA fragmentation in TSGH-8301 cells. CONCLUSIONS:
      Bee venom treatment induces both caspase-dependent and caspase-independent
      apoptotic death through intracellular Ca(2+) -modulated intrinsic death pathway
      in TSGH-8301 cells.

PMID- 22151645
TI  - A molecular and ultrastructural description of Spathidiopsis buddenbrocki and the
      phylogenetic position of the family Placidae (Ciliophora).
AB  - Spathidiopsis and Placus are the only two genera within the family Placidae. The
      family has been placed in the class Prostomatea and order Prorodontida because
      its members have somatic monokinetids with a radial transverse ribbon, a straight
      non-overlapping postciliary ribbon, and anteriorly directed non-overlapping
      kinetodesmal fibril, an apical cytostome lacking specialized oral cilia, a
      brosse, and toxicysts. To confirm the stability of this placement,
      ultrastructural morphology and small subunit rRNA gene sequences of Spathidiopsis
      socialis, Spathidiopsis buddenbrocki, and Placus striatus were determined. These
      data were combined with information from other ciliates, and phylogenetic trees
      were generated using maximum-likelihood and maximum-parsimony methods. The
      analyses confirmed the family Placidae to be a monophyletic group in the
      Prostomatea with the Placidae a sister group to a Cryptocaryon + Coleps +
      Prorodon clade.

PMID- 22151646
TI  - Constraints on genes shape long-term conservation of macro-synteny in metazoan
      genomes.
AB  - BACKGROUND: Many metazoan genomes conserve chromosome-scale gene linkage
      relationships ("macro-synteny") from the common ancestor of multicellular animal
      life 1234, but the biological explanation for this conservation is still unknown.
      Double cut and join (DCJ) is a simple, well-studied model of neutral genome
      evolution amenable to both simulation and mathematical analysis 5, but as we show
      here, it is not sufficent to explain long-term macro-synteny conservation.
      RESULTS: We examine a family of simple (one-parameter) extensions of DCJ to
      identify models and choices of parameters consistent with the levels of macro-
      and micro-synteny conservation observed among animal genomes. Our software
      implements a flexible strategy for incorporating genomic context into the DCJ
      model to incorporate various types of genomic context ("DCJ-[C]"), and is
      available as open source software from http://github.com/putnamlab/dcj-c.
      CONCLUSIONS: A simple model of genome evolution, in which DCJ moves are allowed
      only if they maintain chromosomal linkage among a set of constrained genes, can
      simultaneously account for the level of macro-synteny conservation and for
      correlated conservation among multiple pairs of species. Simulations under this
      model indicate that a constraint on approximately 7% of metazoan genes is
      sufficient to constrain genome rearrangement to an average rate of 25 inversions
      and 1.7 translocations per million years.

PMID- 22151647
TI  - Overview of the BioCreative III Workshop.
AB  - BACKGROUND: The overall goal of the BioCreative Workshops is to promote the
      development of text mining and text processing tools which are useful to the
      communities of researchers and database curators in the biological sciences. To
      this end BioCreative I was held in 2004, BioCreative II in 2007, and BioCreative
      II.5 in 2009. Each of these workshops involved humanly annotated test data for
      several basic tasks in text mining applied to the biomedical literature.
      Participants in the workshops were invited to compete in the tasks by
      constructing software systems to perform the tasks automatically and were given
      scores based on their performance. The results of these workshops have benefited
      the community in several ways. They have 1) provided evidence for the most
      effective methods currently available to solve specific problems; 2) revealed the
      current state of the art for performance on those problems; 3) and provided gold
      standard data and results on that data by which future advances can be gauged.
      This special issue contains overview papers for the three tasks of BioCreative
      III. RESULTS: The BioCreative III Workshop was held in September of 2010 and
      continued the tradition of a challenge evaluation on several tasks judged basic
      to effective text mining in biology, including a gene normalization (GN) task and
      two protein-protein interaction (PPI) tasks. In total the Workshop involved the
      work of twenty-three teams. Thirteen teams participated in the GN task which
      required the assignment of EntrezGene IDs to all named genes in full text papers
      without any species information being provided to a system. Ten teams
      participated in the PPI article classification task (ACT) requiring a system to
      classify and rank a PubMed(r) record as belonging to an article either having or
      not having "PPI relevant" information. Eight teams participated in the PPI
      interaction method task (IMT) where systems were given full text documents and
      were required to extract the experimental methods used to establish PPIs and a
      text segment supporting each such method. Gold standard data was compiled for
      each of these tasks and participants competed in developing systems to perform
      the tasks automatically.BioCreative III also introduced a new interactive task
      (IAT), run as a demonstration task. The goal was to develop an interactive system
      to facilitate a user's annotation of the unique database identifiers for all the
      genes appearing in an article. This task included ranking genes by importance
      (based preferably on the amount of described experimental information regarding
      genes). There was also an optional task to assist the user in finding the most
      relevant articles about a given gene. For BioCreative III, a user advisory group
      (UAG) was assembled and played an important role 1) in producing some of the gold
      standard annotations for the GN task, 2) in critiquing IAT systems, and 3) in
      providing guidance for a future more rigorous evaluation of IAT systems. Six
      teams participated in the IAT demonstration task and received feedback on their
      systems from the UAG group. Besides innovations in the GN and PPI tasks making
      them more realistic and practical and the introduction of the IAT task,
      discussions were begun on community data standards to promote interoperability
      and on user requirements and evaluation metrics to address utility and usability
      of systems. CONCLUSIONS: In this paper we give a brief history of the BioCreative
      Workshops and how they relate to other text mining competitions in biology. This
      is followed by a synopsis of the three tasks GN, PPI, and IAT in BioCreative III
      with figures for best participant performance on the GN and PPI tasks. These
      results are discussed and compared with results from previous BioCreative
      Workshops and we conclude that the best performing systems for GN, PPI-ACT and
      PPI-IMT in realistic settings are not sufficient for fully automatic use. This
      provides evidence for the importance of interactive systems and we present our
      vision of how best to construct an interactive system for a GN or PPI like task
      in the remainder of the paper.

PMID- 22151648
TI  - Evaluating the influence of different aspects of habitat fragmentation on mating
      patterns and pollen dispersal in the bird-pollinated Banksia sphaerocarpa var.
      caesia.
AB  - Habitat fragmentation can significantly affect mating and pollen dispersal
      patterns in plant populations, although the differential effects of the various
      aspects of fragmentation are poorly understood. In this study, we used eight
      microsatellite loci to investigate the effect of fragmentation on the mating
      system and pollen dispersal within one large and eight small population remnants
      of Banksia sphaerocarpa var. caesia, a bird-pollinated shrub in the southern
      agricultural region of Western Australia. The large population had a much larger
      neighbourhood size and lower selfing rate, maternal pollen pool differentiation
      and within-plot mean pollen dispersal distance than the small populations.
      Outcrossing was consistently high and ranged from 85.7% +/- 2.6 to 98.5% +/- 0.9,
      and mating patterns suggested nearest-neighbour pollination. Pollen immigration
      into small populations ranged from 2.8% +/- 1.8 to 16.5% +/- 3.2. Using the small
      populations, we tested for correlations between various fragmentation variables
      and mating system and pollen dispersal parameters. We found significant negative
      linear relationships between population isolation and outcrossing rate;
      population shape and neighbourhood size; and conspecific density and mean pollen
      dispersal distance. There were significant positive linear relationships between
      population shape and pollen pool differentiation and between population size and
      number of different fathers per seed crop. Our results suggest that birds may use
      a series of fragmented populations as a vegetation corridor while foraging across
      the landscape and that population connectivity is a critical determinant of
      pollinator visitation. Our results also suggest that the effect of a linear
      population shape on the mating system and pollen dispersal is routinely
      underestimated.

PMID- 22151649
TI  - Single-incision laparoscopic colectomy without using special articulating
      instruments: an initial experience.
AB  - BACKGROUND: Single-incision laparoscopic colectomy (SILC) was introduced as a
      novel minimally invasive technique. The benefits of this technique include
      reducing number of the incision and cosmetic improvement. Unlike the conventional
      laparoscopic colectomy, majority of previously reported SILC need to be performed
      using special curved or articulated instruments. The purpose of this study is to
      demonstrate our initial experience of SILC, which could be performed using the
      standard laparoscopic instruments. MATERIAL AND METHODS: Retrospective review of
      14 patients who underwent SILC at Siriraj Hospital from May to December 2010,
      patient's demographic data, perioperative outcomes, early postoperative
      complications and pathological data were collected and analyzed. RESULTS: The
      mean age of all patients was 60 years. The most common operation with SILC was
      sigmoidectomy (n = 9), followed by right hemicolectomy (n = 2), left
      hemicolectomy (n = 1), anterior resection (n = 1), and total colectomy (n = 1).
      The trocar insertion techniques were multi-fascial incision using regular port (n
      = 11) and GelPOINT((r)) (n = 3). The mean operative time was 155 minutes (range
      90-280) and the mean estimate blood loss was 32.1 mL (range 10-100). All patients
      were successfully operated without conversion. The mean length of hospital stay
      was 9 days (range 5-20). There was no mortality. The pathological results
      revealed colorectal cancer (n = 12), neoplastic polyp (n = 1) and Familial
      adenomatous polyposis (FAP) (n = 1). The mean number of lymph nodes retrieval was
      16.6 (range 3-34). CONCLUSION: SILC can successfully and safely be performed with
      standard laparoscopic instruments. This technique might be an alternative
      procedure to conventional laparoscopic colectomy with better cosmetic result.

PMID- 22151650
TI  - Comparison of cardiovascular risk factors and survival in patients with ischemic
      or hemorrhagic stroke.
AB  - BACKGROUND: Differences in risk factor profiles between patients with ischemic
      and hemorrhagic stroke may have an impact on subsequent mortality. AIM: To
      explore cardiovascular disease risk factors, including the CHADS(2)  score, with
      survival after ischemic or hemorrhagic stroke. METHODS: Between 2001 and 2005, 87
      111 (83%) ischemic stroke, 12 497 (12%) hemorrhagic stroke, and 5435 (5%)
      patients with unspecified stroke were identified in the Swedish Stroke Register.
      Data on gender, age, and cardiovascular disease risk factors were linked to the
      Swedish Hospital Discharge and Cause of Death Registers. Adjusted odds and hazard
      ratios and 95% confidence interval were calculated using logistic and Cox
      proportional hazard regression models. RESULTS: Hemorrhagic stroke patients were
      younger than ischemic stroke patients. All cardiovascular disease risk factors
      studied, alone or combined in the CHADS(2)  score, were associated with higher
      odds ratios for ischemic stroke vs. hemorrhagic stroke. Higher CHADS(2)  scores
      and all studied risk factors except hypertension were associated with higher odds
      ratio for death by ischemic stroke than hemorrhagic stroke. Ischemic stroke was
      associated with lower early mortality (within 30 days) vs. hemorrhagic stroke
      (hazard ratio = 0.28, confidence interval 0.27 to 0.29). CONCLUSIONS: Patients
      with hemorrhagic stroke had a higher risk of dying within the first 30 days after
      stroke, but the risk of death was similar in the two groups after one-month.
      Hypertension was the only cardiovascular disease risk factor associated with an
      increased mortality rate for hemorrhagic stroke as compared to ischemic stroke.

PMID- 22151651
TI  - Microinfusion of a corticotrophin-releasing hormone receptor 1 antisense
      oligodeoxynucleotide into the dorsal hippocampus attenuates stress responses at
      specific times after stress exposure.
AB  - Corticotrophin-releasing hormone (CRH) plays a key role in the adjustment of
      neuroendocrine and behavioural adaptations to stress. Dysregulation in CRH
      systems has been implicated in a variety of stress-related psychiatric disorders
      such as post-traumatic stress disorder (PTSD). The present study examined the
      relationship between stress-induced PTSD-like behavioural response patterns and
      levels of CRH, CRH receptor (CHR-R)1 and phosphorylated extracellular signal
      regulated kinase (pERK1/2) in the rat hippocampus subregions. The effects of
      pharmacological manipulations on behavioural, physiological and response patterns
      of brain-derived neurotrophic factor (BDNF) and pERK1/2 expression using a CRH
      receptor (CRH-R)1-antisense oligodeoxynucleotide (CRH-R1-ASODN) were evaluated.
      CRH and CRH-R1 mRNA and pERK1/2 protein levels were assessed in the hippocampus
      subregions 7 days after exposure to predator scent stress (PSS). The effects of
      CRH-ASODN versus CRH-Scrambled-ODN microinfusion to the dorsal hippocampus either
      1 h or 48 h post-exposure on behavioural tests (elevated plus maze and acoustic
      startle response) were evaluated 7 days later, 14 days after PSS exposure.
      Localised brain expression of BDNF and ERK1/2 was subsequently assessed. All data
      were analysed in relation to individual behaviour patterns. A distinct pattern
      associated with extreme behavioural response (EBR) was revealed in the bioassay
      of behavioural study subjects, classified according to their individual patterns
      of behavioural response at 7 days. These EBR individuals displayed significantly
      higher CRH and CRH-R1 mRNA levels in the CA1 and CA3 areas, mediating down
      regulation of pERK1/2 protein levels. Microinfusion of a CRH-R1-ASODN into the
      dorsal hippocampus 48 h after stress exposure, although not immediately after
      exposure (1 h), significantly reduced behavioural disruption and was associated
      with concomitant up-regulation of BDNF and pERK1/2 protein levels compared to CRH
      R1-Scrambled -ODN controls. CRH/CRH-R1 is actively involved in the
      neurobiological response to predator scent stress processes and thus warrants
      further study as a potential therapeutic avenue for the treatment of anxiety
      related disorders.

PMID- 22151652
TI  - MMPI Profile as an Outcome "Predictor" in the Treatment of Noncancer Pain
      Patients Utilizing Intraspinal Opioid Therapy.
AB  - Objective. To evaluate changes in Minnesota Multiphasic Personality Inventory
      (MMPI) profiles pre- and post-treatment involving intrathecal opioid therapy.
      Patients and Methods. This study reports on 30 patients that were evaluated pre-
      and post-intraspinal opioid therapy. Treatment duration was slightly more than
      four years. Each patient experienced chronic non-cancer pain deemed suitable for
      trialing and subsequent implantation of a drug administration system (DAS). On
      average the patients had experienced pain for 8.4 years and had a mean of 3.2
      pain-related surgeries. Results. The patients could be divided into "positive
      change group" and "negative change group" based upon pre- and post-treatment MMPI
      profiles. Those patients in the negative change group had more "normal profiles"
      pretreatment. This group evidenced less reduction in pain and was found to be
      using slightly higher levels of intraspinal opioids. Conclusions. These results
      would suggest that the MMPI profile may not be a good "predictor" of long-term
      outcome utilizing intraspinal opioid therapy. Indeed, patients with the more
      normal profile pretreatment did not fare as well as those with the more elevated
      profile. A positive change in MMPI profile from pre- to post-treatment was
      associated with a higher level of pain reduction. Patient selection therefore
      should be based not on a single test such as the MMPI, but on consistency across
      multiple sources of information including physical examination, complaints of
      pain and disability, behavioral observations, and psychological testing.

PMID- 22151653
TI  - Peripheral Subcutaneous Electrostimulation for Control of Intractable Post
      operative Inguinal Pain: A Case Report Series.
AB  - Objective. To present a novel treatment approach for intractable inguinal
      neuralgia utilizing percutaneous peripheral electrostimulation. Materials and
      Methods. We report results of peripheral electrostimulation in three patients who
      experienced onset of inguinal neuralgic pain in the immediate postoperative
      period following herniorrhaphy. In each case pain was refractory to medical
      management and caused significant functional impairment. These three patients
      were first percutaneously trialed and then implanted with dual octipolar
      peripheral nerve stimulators (Advanced Neuromodulation Systems, Plano, TX) in
      close proximity to the injured nerve. Results. All three patients responded very
      favorably (75-100% pain relief at three, 10, and 12 months postimplantation).
      There were no complications. All three tapered off their pain-related medication,
      dramatically increased their levels of activity, and discontinued pain-related
      medical visits. Both patients who were on disability due to inguinal pain have
      been able to return to full-time employment. Conclusion. These preliminary
      results suggest that the technique described is effective and safe, and may be
      cost-effective as well.

PMID- 22151654
TI  - Treatment of failed back surgery syndrome.
AB  - Objectives. To evaluate the long-term results of different therapies for failed
      back surgery syndrome (FBSS). Materials and Methods. From 1992 to 1997, 49
      patients were treated for FBSS. Twenty patients were treated medically. Twenty
      four patients, who did not respond to medical therapy, underwent spinal cord
      stimulator (SCS) implant and five underwent further spine surgery. All patients
      were evaluated by VAS, PDI, and the Oswestry Scales before treatment and at
      follow-up. Leg pain, back pain, work status or daily activities, drug side
      effects, and use of analgesic medications after implantation were examined.
      Follow-up ranged from 24 to 84 months (mean 42 months). Results. At last follow
      up, the patients treated medically demonstrated good results on leg and low back
      pain in eight cases; in other cases, good results were transitory and several
      therapeutic courses were necessary to control the pain. Two patients treated
      medically had substantial side effects. All but two patients treated with SCS
      demonstrated good results for their leg pain; whereas those treated for back pain
      with SCS had poor results. Two patients still needed continuous drug
      administration. Conclusions. Medical therapy is effective for leg and back pain;
      nevertheless, several courses of therapy may be necessary. SCS is an effective
      treatment for leg pain, however, its effectiveness on back pain appears to be
      inadequate.

PMID- 22151655
TI  - Complications of intrathecal drug delivery systems.
AB  - Objectives. To report complications associated with implant of the intrathecal
      drug delivery systems (IDDS). Patients and Methods. A retrospective review of the
      implant database was undertaken to determine various complications associated
      with the IDDS. A total of 122 patients were reviewed, 97 included in the final
      analysis, 25 excluded due to incomplete data. The complications of excluded
      patients were reviewed separately. The complications were divided in to
      categories pharmacologic, equipment, procedural, programming errors and
      psychological. The drugs used were morphine, dilaudid, fentanyl, sufentanil,
      baclofen, and marcaine. Results. There were 60 men and 37 women. A total of 43
      patients reported various complications. Most common were transient pharmacologic
      side effects (n= 33), procedural (n= 5), equipment (n= 16), programming (n= 2),
      and psychological (n= 3). The most serious procedural complication was
      Staphylococcus aureus meningitis (n= 1). Catheter disconnection and leakage was
      noted in (n= 6) patients. Two programming errors were related to increase in drug
      concentration with failure to reduce the dose. Seven pumps were explanted,
      including three due to distorted body image. Conclusion. IDDS are effective and
      safe devices for pain management. The complications associated with implants are
      mostly pharmacological and transient.

PMID- 22151656
TI  - Pump battery assessment: cold, old, or dead!
AB  - Intraspinal drug delivery systems are becoming increasingly utilized for the
      management of patients with pain or spasticity. Numerous potential complications
      associated with the use of this technology have previously been described in the
      literature. We have had experience with a new complication of the internal alarm
      being triggered by the instillation of cold solution into the pump resevoir. This
      new finding could have implications for patients with respect to unnecessary
      reevaluations of the pump, or possible premature scheduling of pump replacement
      surgery.

PMID- 22151657
TI  - Long-term intrathecal ziconotide therapy: a case study and discussion.
AB  - This case study describes the therapeutic result of intrathecal administration of
      ziconotide, a new synthetic neurotoxin derived from the venom of the Philippine
      marine snail, Conus Magus, to a 48-year-old male with chronic, and previously
      untreatable, neuropathic pain of an undeterminable etiology. The patient suffered
      tactile allodynia and reported his baseline pain intensity to be 80 mm on the 100
      mm Visual Analog Scale for Pain Intensity. After responding affirmatively to
      treatment in a blinded placebo-controlled trial, the patient enrolled in a long
      term, open-label trial. Currently, the patient rates his pain at 16 mm and enjoys
      an improved quality of life. This result suggests that treatment with ziconotide
      may provide outstanding relief to patients with chronic pain while sparing them
      the unpleasant side effects associated with other treatments.

PMID- 22151658
TI  - Effect of agonist-antagonist electrical stimulation on muscle afferent recordings
      in anesthetized rabbits.
AB  - Objective. Sensory feedback extracted from muscle afferents is an approach to
      achieve closed-loop control of paralyzed muscles using functional electrical
      stimulation (FES). The objective of the present study was to characterize the
      effect of agonist-antagonist electrical stimulation on nerve cuff recordings of
      muscle afferent activity. Methods. Cuff electrodes were implanted around the
      tibial and peroneal nerve branches in five acute rabbit experiments. Two wires
      were implanted in each of the tibialis anterior (TA) and the lateral
      gastrocnemius (LG) muscles to obtain bipolar, intramuscular stimulation.
      Electroneurograms (ENG) were recorded during trapezoidal rotations of the ankle
      joint and compared during periods (25%, 50% and 100% of maximal force) with and
      without electrical stimulation of the muscle. Results. The activity from a
      stretched and electrically stimulated muscle showed the same pattern as the
      recordings from a matched nonstimulated muscle. The background afferent activity
      increased with increasing level of muscle stimulation. The static and dynamic
      sensitivities were not found to be different, except in one case (peroneal nerve
      at 100% TA recruitment). Discussion. The main contribution to the tibial activity
      was believed to originate from muscle afferents in nonstimulated, synergist
      muscles. The main contribution to the peroneal activity was believed to be from
      muscle afferents within the muscle being stimulated. It was suggested that the
      increased background activity could be attributed to the increased activity of
      the Golgi tendon organs. Conclusions. Sensory information about joint flexion and
      joint extension are preserved in muscle afferent recordings from electrically
      activated muscles at low and intermediate stimulation levels, but it still has to
      be shown whether muscle afferent information can be useful as sensory feedback in
      FES control.

PMID- 22151659
TI  - High sCD40L levels early after trauma are associated with enhanced shock,
      sympathoadrenal activation, tissue and endothelial damage, coagulopathy and
      mortality.
AB  - BACKGROUND: Severe injury activates the sympathoadrenal, hemostatic and
      inflammatory systems, but a maladapted response may contribute to a poor outcome.
      Soluble CD40L is a platelet-derived mediator that links inflammation, hemostasis
      and vascular dysfunction. OBJECTIVES: To investigate the association between the
      sCD40L level and tissue injury, shock, coagulopathy and mortality in trauma
      patients. METHODS: A prospective, observational study of 80 trauma patients
      admitted to a Level I Trauma Center. Data on demography, biochemistry, Injury
      Severity Score (ISS) and 30-day mortality were recorded and admission
      plasma/serum analyzed for sCD40L and biomarkers reflecting sympathoadrenal
      activation (adrenaline, noradrenaline), tissue/endothelial cell/glycocalyx damage
      (histone-complexed DNA fragments [hcDNA], Annexin V, thrombomodulin and syndecan
      1), coagulation activation/inhibition (PF1.2, TAT-complex, antithrombin, protein
      C, activated protein C, sEPCR, TFPI, von Willebrand factor [VWF], fibrinogen and
      factor [F] XIII), fibrinolysis (D-dimer, tissue plasminogen activator [tPA] and
      plasminogen activator inhibitor-1 [PAI-1]) and inflammation (interleukin-6 [IL-6]
      and sC5b-9). We compared patients stratified by median sCD40L level and
      investigated predictive values of sCD40L for mortality. RESULTS: High circulating
      sCD40L was associated with enhanced tissue and endothelial damage (ISS, hcDNA,
      Annexin V, syndecan-1 and sTM), shock (pH, standard base excess), sympathoadrenal
      activation (adrenaline) and coagulopathy evidenced by reduced thrombin generation
      (PF1.2), hyperfibrinolysis (D-dimer), increased activated partial thromboplastin
      time (APTT) and inflammation (IL-6) (all P < 0.05). A higher ISS (P = 0.017),
      adrenaline (P = 0.049) and platelet count (P = 0.012) and lower pH (P =0.002)
      were associated with higher sCD40L by multivariate linear regression analysis.
      High circulating sCD40L (odds ratio [OR] 1.84 [95% CI 1.05-3.23], P = 0.034),
      high age (P = 0.002) and low Glasgow Coma Score (GCS) pre-hospital (P = 0.002)
      were independent predictors of increased mortality. CONCLUSIONS: High early
      sCD40L levels in trauma patients reflect tissue injury, shock, coagulopathy and
      sympathoadrenal activation and predict mortality. As sCD40L has pro-inflammatory
      activity and activates the endothelium, sCD40L may be involved in trauma-induced
      endothelial damage and coagulopathy.

PMID- 22151660
TI  - Continuous versus intermittent spinal cord stimulation: an analysis of factors
      influencing clinical efficacy.
AB  - OBJECTIVES:   Spinal cord stimulation (SCS) has, for decades, been shown to be
      successful in a variety of chronic neuropathic pain syndromes. However, there is
      a paucity of reports in the literature comparing different stimulation patterns.
      The impact of different stimulation patterns upon outcome remains to be
      determined, as well as how the latter is influenced by the duration of the post
      SCS pain-free interval. MATERIALS AND METHODS:   Data from 61 patients (of 71
      eligible patients) were collected by means of a telephone interview. These data
      included the pattern of stimulation (intermittent or continuous), the intensity
      of stimulation with regard to threshold, the mean, maximal, and minimal pain
      strength on a numerical rating scale with and without stimulation, the average
      duration and number of daily stimulation intervals, the average duration of the
      pain-relieving effect after switching off the impulse generator, the pain
      medication intake, the extent of paresthesia coverage, unpleasant side effects,
      and patient satisfaction. RESULTS:   The average improvement in pain score
      following SCS was 3.10 (50.61%). Twenty-four patients (39.3%) performed
      continuous stimulation, and 37 patients (60.7%) performed intermittent
      stimulation. Patients who performed continuous stimulation had significantly
      shorter pain-free intervals following the cessation of stimulation. These
      patients also showed a tendency toward higher pain scores with and without
      stimulation, which was not statistically significant. There were no significant
      differences in pain scores, duration of pain relief, and usage of the stimulation
      system between patients with different diagnoses and lead locations. CONCLUSION: 
      Our data showed an equal effectiveness of SCS in the intermittent and in the
      continuous stimulation mode. The duration of the post-SCS pain-free interval may
      be predictive for the choice of the most effective individual stimulation pattern
      and deserves further investigation.

PMID- 22151661
TI  - Sexual knowledge, attitudes and behaviors among unmarried migrant female workers
      in China: a comparative analysis.
AB  - BACKGROUND: In recent years, many studies have focused on adolescent's sex
      related issues in China. However, there have been few studies of unmarried
      migrant females' sexual knowledge, attitudes and behaviors, which is important
      for sexual health education and promotion. METHODS: A sample of 5156 unmarried
      migrant female workers was selected from three manufacturing factories, two
      located in Shenzhen and one in Guangzhou, China. Demographic data, sexual
      knowledge, attitudes and behaviors were assessed by self-administered
      questionnaires. Multivariate logistic regression analysis was conducted to
      examine the factors associated with premarital sexual intercourse. RESULTS: The
      average age of the unmarried female workers included in the sample was 20.2
      years, and majority of them showed a low level of sex-related knowledge. Females
      from the west of China demonstrated a significant lower level of sex-related
      knowledge than those from the eastern or central provinces (p < 0.05).
      Approximately 13% of participants held a favorable attitude towards premarital
      sexual intercourse, and youths from the east/central were more likely to have
      favorable attitudes compared with those from the west (p < 0.05). About 17.0% of
      the unmarried female workers reported having engaged in premarital sexual
      intercourse, and females from the east/central were more likely to have
      experienced premarital sexual intercourse than those from the west (p < 0.05).
      Multivariate analysis revealed that age, education, current residential type,
      dating, sexual knowledge, attitudes, and pattern of communication were
      significantly associated with premarital sexual intercourse. CONCLUSION: The
      unmarried migrant female workers lack sexual knowledge and a substantial
      proportion of them are engaged in premarital sexual behaviors. Interventions
      aimed at improving their sexual knowledge and related skills are needed.

PMID- 22151663
TI  - Can emergency physicians improve quality of care by using checklists and going
      HOME?

PMID- 22151662
TI  - Interaction of endothelial progenitor cells expressing cytosine deaminase in
      tumor tissues and 5-fluorocytosine administration suppresses growth of 5
      fluorouracil-sensitive liver cancer in mice.
AB  - The drug delivery system to tumors is a critical factor in upregulating the
      effect of anticancer drugs and reducing adverse events. Recent studies indicated
      selective migration of bone marrow-derived endothelial progenitor cells (EPC)
      into tumor tissues. Cytosine deaminase (CD) transforms nontoxic 5-fluorocytosine
      (5-FC) into the highly toxic 5-fluorouracil (5-FU). We investigated the antitumor
      effect of a new CD/5-FC system with CD cDNA transfected EPC for hepatocellular
      carcinoma (HCC) in mice. We used human hepatoma cell lines (HuH-7, HLF, HAK1-B,
      KYN-2, KIM-1) and a rat EPC cell line (TR-BME-2). Escherichia coli CD cDNA was
      transfected into TR-BME-2 (CD-TR-BME). The inhibitory effect of 5-FU on the
      proliferation of hepatoma cell lines and the inhibitory effect of 5-FU secreted
      by CD-TR-BME and 5-FC on the proliferation of co-cultured hepatoma cells were
      evaluated by a tetrazolium-based assay. In mouse subcutaneous xenograft models of
      KYN-2 and HuH-7, CD-TR-BME was transplanted intravenously followed by 5-FC
      injection intraperitoneally. HuH-7 cells were the most sensitive to 5-FU and KYN
      2 cells were the most resistant. CD-TR-BME secreted 5-FU and inhibited HuH-7
      proliferation in a 5-FC dose-dependent manner. CD-TR-BME were recruited into the
      tumor tissues and some were incorporated into tumor vessels. Tumor growth of HuH
      7 was significantly suppressed during 5-FC administration. No bodyweight loss,
      ALT abnormality or bone marrow suppression was observed. These findings suggest
      that our new CD/5-FC system with CD cDNA transfected EPC could be an effective
      and safe treatment for suppression of 5-FU-sensitive HCC growth.

PMID- 22151664
TI  - Should reading a journal article really change my practice?

PMID- 22151665
TI  - Review article: Prehospital fluid management in traumatic brain injury.
AB  - The early management of patients who have sustained traumatic brain injury is
      aimed at preventing secondary brain injury through avoidance of cerebral hypoxia
      and hypoperfusion. Especially in hypotensive patients, it has been postulated
      that hypertonic crystalloids and colloids might support mean arterial pressure
      more effectively by expanding intravascular volume without causing problematic
      cerebral oedema. We conducted a systematic review to investigate if hypertonic
      saline or colloids result in better outcomes than isotonic crystalloid solutions,
      as well as to determine the safety of minimal volume resuscitation, or delayed
      versus immediate fluid resuscitation during prehospital care for patients with
      traumatic brain injury. We identified nine randomized controlled trials and one
      cohort study examined the effects of hypertonic solutions (with or without
      colloid added) for prehospital fluid resuscitation. None has reported better
      survival and functional outcomes over the use of isotonic crystalloids. The only
      trial of restrictive resuscitation strategies was underpowered to demonstrate its
      safety compared with aggressive early fluid resuscitation in head injured
      patients, and maintenance of cerebral perfusion remains the top priority.

PMID- 22151666
TI  - Optimal management of mental health patients in Australian emergency departments:
      barriers and solutions.
AB  - OBJECTIVES: The study aimed to describe: (i) the perceived barriers faced by
      emergency clinicians in the assessment and management of patients presenting with
      a mental health complaint to Australian hospital EDs; and (ii) perceived
      strategies to optimize care of the mentally unwell in the ED. METHODS:
      Semistructured interviews with open and closed question formats were used to
      explore the barriers perceived by ED doctors and nurses in assessing and managing
      patients with mental health presentations. Interviews were transcribed verbatim
      and thematically coded by two researchers using the Framework Approach. RESULTS:
      Thirty-six interviews were conducted with 20 members of the Australasian College
      for Emergency Medicine and 16 members of the College of Emergency Nursing
      Australasia representing the various Australian jurisdictions. Thematic analyses
      revealed that a range of resource, environmental, staff and patient factors
      contribute to difficulties in managing mental health patients. Solutions
      suggested by interviewees included improved resources, ED redesign and improved
      links to resources outside the ED. An overwhelming majority of participants
      perceived the need for more educational opportunities in mental health.
      CONCLUSION: Although the provision of timely and quality care is expected for all
      patients attending EDs, there exist multiple barriers to provision of adequate
      care for ED patients presenting with mental illness. Many of these are systems
      based and thus require systems-based solutions. ED clinician's perceive that
      improved educational opportunities in mental health, however, might alleviate
      some barriers they face. Consideration should be given to a comprehensive,
      quantitative mental health-related learning needs analysis of ED clinicians.

PMID- 22151667
TI  - Increasing impact of mental health presentations on New South Wales public
      hospital emergency departments 1999-2006.
AB  - OBJECTIVE: The percentage of mental health (MH) presentations to New South Wales
      (NSW) EDs in recent years has not been described at the statewide level. Evidence
      from other states suggests this burden might be increasing. The present study
      aims to evaluate recent trends in MH presentations to NSW EDs, including
      geographic variations and the spectrum of MH disorders encountered. METHODS: Data
      were sourced from the NSW Emergency Department Data Collection, which collates
      information from routine reporting undertaken in all NSW EDs. The database
      employs ICD-9 diagnostic descriptors. The present study retrospectively analyses
      presentations from 1999 to 2006 for patients who received an MH primary discharge
      diagnosis, as defined by ICD-9. In addition, rates of presentation for poisoning
      are considered. The percentage of MH presentations to the three largest hospital
      categories--principal referral, major metropolitan and rural base (i.e. major non
      metropolitan)--is examined. RESULTS: During 1999 and 2006, there were 9,013,357
      ED presentations at the study sites. Of these, 3.22% received an MH primary
      discharge diagnosis. An additional 0.93% received a diagnosis of poisoning. In
      2006, there were 15,262 more MH presentations than in 1999, a 49.78% increase.
      Over this period, total annual ED presentations increased by 201,763 (19.30%).
      General population growth was 6.31%. Across the state, 32.0% of MH presentations
      were for psychotic conditions and 68.0% for neurotic illnesses. CONCLUSION:
      Mental health presentations to NSW EDs are increasing. There is a need to review
      emergency services to accommodate these changes. The reasons for this growth
      remain unclear and require formal prospective evaluation.

PMID- 22151668
TI  - Mental health-related learning needs of clinicians working in Australian
      emergency departments: a national survey of self-reported confidence and
      knowledge.
AB  - OBJECTIVE: To identify the mental health-related learning needs of doctors and
      nurses working in Australian EDs. METHODS: A purpose-designed survey was
      developed, and face validity was verified by 12 doctors and nurses. A cross
      sectional survey of a national sample of nurses and senior doctors (registrars
      and consultants) working in EDs across Australia was then undertaken. The survey
      consisted of 130 items and required approximately 20 min for completion. The
      survey was delivered online through email invitation by the College of Emergency
      Nurses Australasia or the Australasian College for Emergency Medicine. A hardcopy
      format of the survey was also delivered at a national conference. RESULTS: Mental
      health presentations that involved a diagnosis of personality disorder, psychosis
      or behavioural disturbance, and the management of these conditions were patient
      factors that were considered problematic by up to 46.3% (118/255; 95% CI 40.26
      52.40) of doctors and 66.1% (72/109; 95% CI 56.74-74.28) of nurses. Determining
      care plans, conducting mental status examinations, assessing risk of self-harm,
      pharmacology for treatment and for chemical restraint, management of patient
      aggression or violence, and alcohol or drug intoxication were also found to be
      areas of knowledge deficit. CONCLUSION: Doctors and nurses reported deficits in
      confidence and knowledge in tasks and patient presentations that they might
      frequently be expected to manage. These data can be used to inform future
      curricula at both undergraduate and postgraduate levels. Ultimately, this might
      pave the way for improved care and management of patients with mental health
      problems presenting to the ED.

PMID- 22151669
TI  - Exercise-associated hyponatraemia on the Kokoda Trail.
AB  - OBJECTIVE: The objective of the present study was to determine the prevalence of
      exercise-associated hyponatraemia in hikers/trekkers along the Kokoda Trail.
      METHODS: This was a cross-sectional study of 191 trekkers on the Kokoda Trail,
      Papua New Guinea. Blood was taken and analysed immediately using point-of-care
      technology 2 days walk from each end of the Trail. RESULTS: The main outcome
      measure was hyponatraemia defined as serum sodium level less than 135 mmol/L.
      Three participants (1.6%, 95% CI 0.5-4.5%) were found to have mild hyponatraemia.
      The hyponatraemic group had a median estimated fluid intake on the day of testing
      that was almost double that of the normal sodium group (6 L vs 3.3 L).
      CONCLUSION: Exercise-associated hyponatraemia occurs in trekkers on the Kokoda
      Trail. Strategies for prevention of exercise-associated hyponatraemia should be
      delivered to trekkers via the trekking companies, chiefly focussing on only
      drinking in response to thirst.

PMID- 22151670
TI  - Comparison of two clinical scoring systems for emergency department risk
      stratification of suspected acute coronary syndrome.
AB  - OBJECTIVE: To compare two methods of risk stratification for suspected acute
      coronary syndrome (ACS) in the ED. METHODS: A prospective observational
      multicentre study was undertaken of patients undergoing evaluation in the ED for
      possible ACS. We compared the National Heart Foundation of Australia/Cardiac
      Society of Australia and New Zealand (NHF/CSANZ) guideline and the Thrombolysis
      in Myocardial Infarction (TIMI) risk score for differentiating high- and low-risk
      patients. Composite outcome was all cause death, myocardial infarction or
      coronary revascularisation within 30 days. RESULTS: Of 1758 enrolments, 223 (13%)
      reached the study outcome. Area under the receiver operator characteristic (ROC)
      curve was 0.79 (95% CI 0.76-0.81) for the NHF/CSANZ group and 0.71 (0.68-0.75)
      for TIMI score based on initial troponin result (P<0.001), and 0.82 (95% CI 0.80
      0.84) and 0.76 (0.73-0.79) respectively when the 8-12 h troponin result is
      included (P=0.001). Thirty day event rates were 33% for NHF/CSANZ high-risk vs
      1.5% for combined low/intermediate risk (P<0.001). For TIMI score, 30 day event
      rates were 23% for a score >=2 and 4.8% for TIMI<2 (P<0.001). The NHF/CSANZ
      guideline identified more patients as low risk compared with the TIMI risk score
      (61% vs 48%, P<0.001). CONCLUSIONS: The NHF/CSANZ guideline is superior to the
      TIMI risk score for risk stratification of suspected ACS in the ED.

PMID- 22151671
TI  - Impact of technical assistants for venepuncture and intravenous cannulation on
      overall emergency department performance.
AB  - OBJECTIVE: The objective of the article was to determine the effect of a
      technical assistant for venepuncture and i.v. cannulation on triage performance
      and patient length of stay in an ED. METHODS: An observational study of daily ED
      performance was conducted at an inner city tertiary referral ED. Over a period of
      158 consecutive days, data on triage performance and average length of stay were
      collected. A technical assistant was employed for 8-10 h per day to perform
      venepuncture, i.v. cannulation and electronic order entry. Study groups compared
      were days staffed by a technical assistant and days that were not staffed.
      RESULTS: Days staffed by a technical assistant were associated with significantly
      higher triage performance for triage category three (mean 0.66, 95% CI 0.63-0.69
      vs 0.58, 95% CI 0.54-0.62; P=0.003) and lower average length of stay per patient
      for triage category two patients (mean length of stay 390 min, 95% CI 369-411 vs
      425 min, 95% CI 399-451; P=0.04). Triage performance thresholds for triage
      category three (75% of patients seen within 30 min) were met over twice as often
      on staffed days compared with control (39/96 [38%]vs 10/62 [16%], P=0.004).
      CONCLUSION: Staffing the ED with a technical assistant was associated with
      improved ED performance for triage category three and average length of stay for
      triage category two patients.

PMID- 22151672
TI  - Sedation assessment tool to score acute behavioural disturbance in the emergency
      department.
AB  - OBJECTIVE: The objective of the study was to evaluate the effectiveness of the
      sedation assessment tool (SAT) in assessing patient response to treatment for
      acute behavioural disturbance (ABD). METHODS: The SAT is a simplified version of
      the altered mental status score (AMSS) and is a 7-point scale assessing levels of
      agitation and sedation using only two descriptors. To assess the SAT we firstly
      compared plots of the SAT and the AMSS versus time in patients with ABD recruited
      to a clinical trial. AMSS were converted to the SAT for this comparison. Second,
      the sensitivity and specificity were calculated for an increase in the SAT to +2
      or +3 as a predictor of whether additional sedation was required in a prospective
      cohort of 138 patients. Third, interrater reliability was assessed using two
      individuals to score the same patient at two different time points and finally
      the time to record the score was measured. RESULTS: Plots of AMSS and SAT for 91
      patients in the clinical trial illustrated similar trends in agitation/sedation.
      Seventeen of 138 patients in the second cohort had an increase in the SAT.
      Fifteen of 17 (88%) received additional sedation. The sensitivity and specificity
      of the SAT for additional sedation was 100% (95% CI 75-100%) and 98% (95% CI 94
      100%), respectively. The median time for staff to assign the SAT was 10 s (range
      3-15 s). Interrater reliability was high with a kappa of 0.87. CONCLUSION: The
      SAT is a simple, rapid and useful measure of the level of agitation/sedation in
      patients with ABD. Increases in the score reliably indicated the need for further
      sedation.

PMID- 22151673
TI  - Teaching medical students to resuscitate children: an innovative two-part
      programme.
AB  - OBJECTIVE: The objective of the present study was to design and evaluate a novel,
      'blended learning' approach to the teaching of paediatric resuscitation to
      medical students. METHODS: Participants were recruited from the Graduate Medical
      Program at the University of Sydney. The course incorporated an initial e
      learning module and a subsequent practical component. The e-learning module
      taught basic and advanced life support. Students then attended a 90 min practical
      session, which focussed on team work and the psychomotor components of
      resuscitation. Improvement in knowledge was measured by a multiple choice
      question (MCQ) test. The MCQ was completed prior to beginning the whole course,
      after completion of the e-learning module and again at follow up 8 months later.
      Students also completed an evaluation survey. RESULTS: Twenty-one students
      participated. There was a significant objective increase in knowledge from pre
      course to post e-learning scores, median scores (interquartile range) from 12/23
      (10.5 to 13.5) to 21/23 (20 to 22.5), P < 0.001. This significant increase in
      knowledge was still apparent at follow up 8 months later. Median MCQ score at
      follow up was 17/23 (14 to 18.5), P < 0.002. Students self-rated significant
      improvements in their knowledge, confidence and ability to perform basic and
      advanced life support for the whole course and between individual components (P <
      0.001). CONCLUSIONS: A novel paediatric resuscitation course for medical students
      was developed and evaluated. This demonstrated significant objective improvements
      in student knowledge throughout the course, at course completion and at 8 month
      follow up. There were also significant subjective improvements in knowledge,
      confidence and ability to perform paediatric resuscitation.

PMID- 22151674
TI  - Predicting the impact on workload with the application of inpatient clinical
      review criteria into a paediatric emergency department.
AB  - OBJECTIVE: Inpatient paediatric clinical observation charts that have predefined
      physiological criteria, which when reached might generate a mandatory medial
      review, are to be introduced into EDs in New South Wales. The present study
      estimated the increased workload of introducing these charts. METHODS: The
      present study was carried out in the ED of The Children's Hospital at Westmead,
      Sydney, Australia. All patients admitted directly to the inpatient wards or to
      the Emergency Medical Unit for a 2 week period in April 2010 were included. The
      last set of clinical observations prior to the child being transferred out of the
      ED were recorded. These data were compared to the review criteria defined by the
      observation charts. The primary outcome was a possible activation of a review.
      Secondary outcomes were an attempt to quantify the extra time in the ED required
      before the review would be completed and the patient would be ready for transfer.
      RESULTS: There were 1822 presentations. Two hundred and fifty-three were admitted
      to the wards and 109 to the Emergency Medical Unit. There were 126 possible
      activations. Fifty-seven (52%) of Emergency Medical Unit patients and 69 (28%) of
      ward patients met review criteria at the time of transfer. The review activations
      might have generated an extra 7060 min of additional workload. CONCLUSIONS:
      Individual units must decide where in the patient journey to introduce the charts
      for acute paediatric admissions based on the number of acute paediatric
      admissions and their severity as well as the availability and ability of staff to
      respond to calls.

PMID- 22151675
TI  - Major trauma deaths at Perth secondary hospitals.
AB  - OBJECTIVE: Some major trauma (Injury Severity Score [ISS] >15) patients
      transported to a secondary hospital in Perth do not survive. We sought to
      describe this cohort and assess preventability. METHODS: A cohort study from a
      previously developed cohort of trauma deaths in Western Australia from 1 July
      1997 to 30 June 2006. A preformatted data sheet was used to collect a range of
      descriptive, time, physiological, and autopsy data. Trauma scores were
      calculated. Preventability was assessed using three approaches, based on ISS,
      Trauma Revised Injury Severity Score (TRISS) and individual case review. RESULTS:
      There were 74 major trauma deaths, mean age 55.6 +/- 26.3 years (range 3-95).
      Thirty-seven (50%) were motor vehicle crashes. The mean Revised Trauma Score was
      3.84 +/- 3.09 (0-7.84), median ISS 31 (interquartile range [IQR] 25-51), median
      TRISS 0.127 (IQR 0.031-0.772) and median time to death was 80 min (IQR 20 min-10
      h 8 min). Severe head and chest injuries were the most common. Almost half (36,
      48.6%) were receiving CPR on arrival to the hospital. The crude proportion of
      potentially preventable deaths, based on ISS, TRISS and case review, were 16.2%,
      32.4% and 6.7%, respectively. However, these were predominantly elderly patients
      and a decision against resuscitation was recorded in 54%. CONCLUSIONS: The
      proportion of potentially preventable major trauma deaths at Perth secondary
      hospitals is low. The most notable group were the elderly after falls, and trauma
      system efforts should be focused on this group. Primary prevention of major
      trauma represents the biggest opportunity for improvements in trauma survival.

PMID- 22151676
TI  - Nitrous oxide/oxygen compared with fentanyl in reducing pain among adults with
      isolated extremity trauma: a randomized trial.
AB  - OBJECTIVE: To compare the effectiveness of nitrous oxide/oxygen (N(2)O/O(2)) and
      fentanyl in relieving pain among patients with an isolated long bone fracture or
      main joint dislocation of the limbs. METHODS: Patients with isolated long bone
      fracture or main joint dislocation with moderate to severe pain were randomized
      into two groups. For the first group, nitrous oxide/oxygen (50:50) was self
      administered until pain relief was achieved up to a maximum of 15 min. Fentanyl
      (2 ug/kg) as a single dose was administered for the second group. Pain intensity
      was measured with a visual analogue scale before and at minutes three, six and
      nine after the start of the drug administration. We also recorded observed
      adverse effects in these two groups. RESULTS: One hundred patients were enrolled
      in the study. No statistically significant difference in pain score was detected
      between the two groups with one exception. The mean visual analogue scale scores
      at 9 min were 2.2 and 3.1 for nitrous oxide/oxygen and fentanyl, respectively
      (difference -0.9 [95% CI -1.7- -0.1]) (P=0.006). There was no statistically
      significant difference between two groups regarding adverse effects. CONCLUSIONS:
      Neither nitrous oxide/oxygen or fentanyl appeared to be superior to the other in
      relieving moderate to severe pain among emergency patients presenting with
      isolated limb fracture or dislocation. In an ED, increased use of nitrous oxide
      might reduce the overall need for opiate analgesia, and in our setting, the need
      for constant monitoring.

PMID- 22151677
TI  - Decontamination and enhanced elimination in sustained-release potassium chloride
      poisoning.
AB  - Potassium chloride poisoning can be potentially life-threatening, particularly in
      massive ingestions of sustained-release preparations. Profound hyperkalaemia,
      developing over several hours, can lead to cardiac arrhythmias and death. This
      case series reports three episodes of sustained-release potassium chloride
      poisoning in two individuals requiring whole bowel irrigation or haemodialysis.
      The first two episodes, in the same patient, illustrate the contrast between the
      successful use of decontamination versus the need for haemodialysis. The second
      case, in a child, illustrates the need for tertiary level paediatric expertise in
      managing this type of poisoning. Whole bowel irrigation with polyethylene glycol
      is a resource-intensive procedure most beneficial when large numbers of radio
      opaque tablets are seen in the stomach. In cases where most of the tablet matter
      has already been absorbed, extracorporeal methods of rapidly reducing the total
      body burden of potassium, such as haemodialysis, might be life-saving.

PMID- 22151678
TI  - Severe hypothermia in myxoedema coma: a rewarming by extracorporeal circulation.
AB  - Myxoedema coma is the most lethal manifestation of hypothyroidism. It represents
      a true medical emergency, especially in the case of cardiovascular instability.
      Extracorporeal circulation is usually used for rewarming and for providing
      cardiac support in patients with severe hypothermia and, in addition,
      cardiovascular instability. We report the case of an 84-year-old woman who
      presented to the ED with accidental hypothermia associated with myxoedema that
      was successfully managed by veno-arterial extracorporeal blood rewarming. This
      case suggests that veno-arterial extracorporeal rewarming appears to achieve a
      rapid and consistent rewarming rate and is less invasive and more readily
      available than cardiopulmonary bypass.

PMID- 22151679
TI  - Sudden near-fatal tracheal aspiration of an undiagnosed nasal foreign body in a
      small child.
AB  - Foreign body aspiration is a commonly encountered emergency in children. Foreign
      body can lodge in any site from supra-glottis to the terminal bronchioles.
      Symptoms might range from none to respiratory compromise, cardiac arrest and even
      death depending on location and size. We report successful management of a child
      who aspirated a nasal foreign body during physical examination in an outpatient
      department causing complete airway obstruction with special mention about
      different management options available for managing near total respiratory arrest
      from an aspirated foreign body in the ED.

PMID- 22151680
TI  - Is the Australasian College for Emergency Medicine trainee research project bar
      now too high?

PMID- 22151681
TI  - Ocular emergencies and using the latest text resources.

PMID- 22151682
TI  - Four-hour access targets for emergency departments: potential negative
      implications for the work practices and clinical training of junior doctors.

PMID- 22151683
TI  - Impact of the 4-hour emergency department target on medical student education.

PMID- 22151685
TI  - International Society of Sports Nutrition: 8th Annual ISSN Conference and Expo
      Las Vegas, NV, USA.  24-25 June 2011. Abstracts.

PMID- 22151684
TI  - Evaluating the extent of potential resistance to pre-exposure prophylaxis within
      the UK HIV-1-infectious population of men who have sex with men.
AB  - OBJECTIVES: Recent studies have shown that pre-exposure prophylaxis (PrEP) can
      substantially reduce the chance of acquiring HIV infection. However, PrEP
      efficacy has been found to be compromised in macaque studies if the challenge
      virus is antiretroviral therapy (ART)-resistant. Our objective was to evaluate
      the likelihood that a UK man who has sex with men (MSM) would be exposed to PrEP
      resistant HIV in a homosexual encounter with an HIV-infectious partner. METHODS:
      Data from the UK Collaborative HIV Cohort (UK CHIC) study were linked to the UK
      HIV Drug Resistance Database for HIV-1-positive MSM patients seen between 2005
      and 2008. Patients were categorized as undiagnosed; diagnosed but ART-naive; ART
      experienced and on treatment; and ART-experienced and on a treatment
      interruption. Considering current PrEP regimens, resistance to (a) tenofovir
      (TDF) alone, (b) TDF and emtricitabine (FTC), and (c) TDF or FTC was estimated.
      Patients without resistance tests had PrEP resistance imputed using bootstrapping
      and logistic regression models. RESULTS: The population-level prevalence of PrEP
      resistance in HIV-infectious individuals in 2008 was estimated to be 1.6, 0.9 and
      4.1% for PrEP resistance definitions a, b and c, respectively. Prevalence in ART
      experienced patients was highest, with negligible circulating resistance amongst
      ART-naive individuals. The levels of resistance declined over the period of
      study. CONCLUSIONS: Our analysis indicates low levels of resistance to proposed
      PrEP drugs. The estimated PrEP resistance prevalence in UK HIV-infected MSM is
      towards the lower range of values used in simulation studies which have suggested
      that circulating PrEP drug resistance will have a negligible impact on PrEP
      efficacy at the population level.

PMID- 22151686
TI  - Harm reduction interventions for drug injectors or heroin users in Spain:
      expanding coverage as the storm abates.
AB  - AIMS: To show the utility of analysing time trends of need and coverage of needle
      exchange programmes (NEPs) and opioid substitution treatment (OST) to assess harm
      reduction policies targeting drug injectors or heroin users. DESIGN: Multiple
      methods applied to secondary data. SETTING: Spain. PARTICIPANTS: Thousands of
      drug injectors or heroin users included in administrative registers, surveys and
      published studies during 1987-2010. MEASUREMENTS: Coverage for the general
      population was calculated as the ratio between interventions provided (obtained
      directly from the sources) and interventions needed (estimated by multiple
      methods), and as the difference between the two. Timeliness was estimated by time
      elapsed between year of highest need and year in which coverage reached a
      reference level. FINDINGS: In 2010 NEPs provided 138 syringes per drug injector
      [95% confidence interval (CI) 100-223], covering 25.7% (95% CI 18.3-43.3) of
      their need. OST coverage was 60.3% (95% CI 44.3-94.2). Syringe and OST provision
      increased between 1991 and 2001 and then declined. Syringe and OST coverage also
      increased substantially during this period and then stabilized, due mainly to
      decreases in drug injection or heroin use. Medium-level coverage for both
      syringes and OST was not achieved until 2000, 8 years after the peak in need
      (1992). CONCLUSIONS: In Spain, the expansion of harm reduction interventions was
      greatly delayed, although the concomitant decrease in heroin and injecting drug
      use led to reasonable coverage after 2000. A longitudinal measurement of need and
      coverage provides insight into the timeliness and potential population impact of
      interventions, enabling better assessment of their adequacy.

PMID- 22151687
TI  - Molecular detection and speciation of pathogenic Leptospira spp. in blood from
      patients with culture-negative leptospirosis.
AB  - BACKGROUND: Pathogenic Leptospira spp. present in the blood of patients with
      leptospirosis during the first week of symptoms can be detected using culture or
      PCR. A proportion of patients who are positive by PCR are negative by culture.
      Leptospira spp. are fastidious bacteria, and we hypothesized that a false
      negative culture result may represent infection with a distinct bacterial subset
      that fail to grow in standard culture medium. METHODS: We evaluated our
      hypothesis during a prospective study of 418 consecutive patients presenting to a
      hospital in northeast Thailand with an acute febrile illness. Admission blood
      samples were taken for Leptospira culture and PCR. A single tube nested PCR that
      amplified a region of the rrs gene was developed and applied, amplicons sequenced
      and a phylogenetic tree reconstructed. RESULTS: 39/418 (9%) patients were culture
      positive for Leptospira spp., and 81/418 (19%) patients were culture-negative but
      rrs PCR-positive. The species associated with culture-positive leptospirosis (37
      L. interrogans and 2 L. borgpetersenii) were comparable to those associated with
      culture-negative, PCR-positive leptospirosis (76 L. interrogans, 4 L.
      borgpetersenii, 1 unidentified, possibly new species). CONCLUSION: Molecular
      speciation failed to identify a unique bacterial subset in patients with culture
      negative, PCR-positive leptospirosis. The rate of false-negative culture was
      high, and we speculate that antibiotic pre-treatment is the most likely
      explanation for this.

PMID- 22151688
TI  - Bone quality and quantity of the anterior maxillary trabecular bone in dental
      implant sites.
AB  - OBJECTIVES: The aim of this study was to investigate the characteristics of
      implant sites on the edentulous alveolar ridge in the anterior maxilla. We
      studied the bone quantity and quality of implant sites at the anterior maxilla
      using CT images for the 33 implant sites on patients who underwent dental implant
      therapy in our Department since 2006. MATERIALS AND METHODS: Computed tomography
      (CT) images of 33 patients (20 women: 13 men) encompassing 33 implant sites were
      chosen and examined. The recipient sites for implant placement were determined
      based on CT data using an implant planning software (Simplant 11.0). The mean
      bone density values in Hounsfield unit (HU) were recorded using Simplant for both
      the simulated implant areas and the trabecular bone width. We classified the
      edentulous alveolar ridge and bone quality according to a classification based on
      Lekholm and Zarb (1985). RESULTS: Incisors had higher bone densities than
      canines. Women had lower bone densities than men. Canines displayed greater
      trabecular bone density and alveolar bone widths than incisors. No maxillary
      sites were judged to have a bone quality of 1 in this group. Quality 3 accounted
      for 69.7% of the total samples. CONCLUSIONS: An assessment of bone quality in the
      anterior alveolar ridge may well reflect age-related systemic pathological
      conditions and should be used in dental implant treatment planning to avoid
      associated risk factors.

PMID- 22151689
TI  - Healthcare utilization and costs in patients beginning pharmacotherapy for
      generalized anxiety disorder: a retrospective cohort study.
AB  - BACKGROUND: Patterns of healthcare utilization and costs in patients beginning
      pharmacotherapy for generalized anxiety disorder (GAD) have not been well
      characterized. METHODS: Using a large US health insurance database, we identified
      all patients with evidence of GAD (ICD-9-CM diagnosis code 300.02) who initiated
      pharmacotherapy with medications commonly used to treat GAD (eg, selective
      serotonin reuptake inhibitors [SSRIs], venlafaxine, benzodiazepines) between
      1/1/2003 and 12/31/2007. We examined healthcare utilization and costs over the 12
      month periods preceding and following date of initial receipt of such therapy
      ("pretreatment" and "follow-up", respectively). Patients with incomplete data
      were excluded. RESULTS: A total of 10,275 patients met all study inclusion
      criteria. Forty-eight percent of patients received SSRIs; 34%, benzodiazepines;
      and 6%, venlafaxine. SSRIs and venlafaxine were about three times more likely to
      be used on a long-term basis (> 90 days) than benzodiazepines (p < 0.01). In
      general, levels of healthcare utilization were higher during follow-up than
      pretreatment. Mean (SD) total healthcare costs increased from $4812 ($10,006)
      during pretreatment to $7182 ($22,041) during follow-up (p < 0.01); costs of GAD
      related pharmacotherapy during follow-up were $420 ($485). CONCLUSIONS: More than
      one-half of patients initiating pharmacotherapy for GAD receive either SSRIs or
      venlafaxine. Levels of healthcare utilization and costs are greater in the year
      following initiation of therapy than in the immediately preceding one.

PMID- 22151690
TI  - Coronary patients who returned to work had stronger internal locus of control
      beliefs than those who did not return to work.
AB  - OBJECTIVES: Return To Work (RTW) is an important indicator of recovery from
      coronary artery disease (CAD), associated with social and economical benefits,
      and improved quality of life. Percutaneous coronary intervention (PCI) and
      coronary artery bypass graft (CABG) surgery are effective procedures relieving
      symptoms and reducing the risk for new events, but psychosocial problems are
      frequent among these patients. The aim was to determine psychosocial and
      treatment-related factors associated with RTW among PCI and CABG patients in
      Northern Norway. DESIGN: Cross-sectional design based on questionnaire data from
      CABG and PCI patients 3-15 months following discharge, and from hospital records.
      METHODS: Of the 348 responding patients, 168 were younger than 67 years and
      working prior to hospitalization. Factors associated with RTW were examined in a
      logistic regression analysis. RESULTS: A total of 108 (64%) had RTW within 3-15
      months. Four factors made unique significant contributions to the model,
      including higher education, time since hospital discharge and Internal Locus of
      Control (LoC) of the Multidimensional Health Locus of Control Scale (MHLC) as
      positively associated factors, and Powerful Others LoC as a negatively associated
      factor. Analyses controlled for data on demographics, emergency status, type of
      treatment, number of days at the hospital, physical exercise, attending a
      rehabilitation program, mental distress, Type D personality, and for the CABG
      patients additional data on coronary health. CONCLUSIONS: Patients' control
      beliefs and educational level are significant psychosocial factors associated
      with RTW following PCI and CABG treatment. Implications for hospital treatment
      and rehabilitation programs are discussed.

PMID- 22151692
TI  - Bone resorption and environmental exposure to cadmium in children: a cross-
      sectional study.
AB  - BACKGROUND: Exposure to cadmium has been associated with osteoporosis and
      fracture risk in women and elderly, but studies in children are lacking. In the
      present study we investigate the association between markers of bone
      demineralization [urinary calcium (Ca) and deoxypyridinoline (DPD) excretion] and
      urinary cadmium (Cd) excretion (as an index of lifetime body burden). METHODS:
      155 schoolchildren from 2 elementary schools in Lahore, Pakistan were included.
      Urinary Cd was measured as an index of lifetime exposure. We assessed the
      multivariate-adjusted association of exposure with markers of bone resorption,
      urinary DPD as well as with Ca excretion. RESULTS: Urinary Cd averaged 0.50
      nmol/mmol creatinine and was not influenced by age, height, weight and socio
      economic status (SES). Independent of gender, age, height, weight and SES a
      doubling of urinary Cd was associated with a 1.72 times (p < 0.0001) increase in
      urinary DPD and, a 1.21 times (p = 0.02) increase in urinary Ca. Additional
      adjustment for urinary Ca revealed still significant associations between urinary
      Cd and urinary DPD. The shape of the association was linear without evidence of a
      threshold. CONCLUSIONS: Even in young children, low-level environmental exposure
      to cadmium is associated with evidence of bone resorption, suggesting a direct
      osteotoxic effect with increased calciuria. These findings might have clinical
      relevance at older age.

PMID- 22151691
TI  - Deep mitochondrial divergence within a Heliconius butterfly species is not
      explained by cryptic speciation or endosymbiotic bacteria.
AB  - BACKGROUND: Cryptic population structure can be an indicator of incipient
      speciation or historical processes. We investigated a previously documented deep
      break in the mitochondrial haplotypes of Heliconius erato chestertonii to explore
      the possibility of cryptic speciation, and also the possible presence of
      endosymbiont bacteria that might drive mitochondrial population structure.
      RESULTS: Among a sample of 315 individuals from 16 populations of western
      Colombia, two principal mtDNA clades were detected with 2.15% divergence and we
      confirmed this structure was weakly associated with geography. The first mtDNA
      clade included 87% of individuals from northern populations and was the sister
      group of H. erato members of Andes western, while the second clade contained most
      individuals from southern populations (78%), which shared haplotypes with an
      Ecuadorian race of H. erato. In contrast, analysis using AFLP markers showed H.
      e. chestertonii to be a genetically homogeneous species with no association
      between mitochondrial divergence and AFLP structure. The lack of congruence
      between molecular markers suggests that cryptic speciation is not a plausible
      explanation for the deep mitochondrial divergence in H. e chestertonii. We also
      carried out the first tests for the presence of endosymbiontic bacteria in
      Heliconius, and identified two distinct lineages of Wolbachia within H. e.
      chestertonii. However, neither of the principal mitochondrial clades of H. e.
      chestertonii was directly associated with the patterns of infection. CONCLUSIONS:
      We conclude that historical demographic processes are the most likely explanation
      for the high mitochondrial differentiation in H. e. chestertonii, perhaps due to
      gene flow between Cauca valley H. e. chestertonii and west Pacific slope
      populations of H. erato.

PMID- 22151693
TI  - Distribution of glial fibrillary acidic protein accumulation after retinal tack
      insertion for intraocular fixation of epiretinal implants.

PMID- 22151694
TI  - Editorial Comment to Renoprotective effect of erythropoietin in
      ischemia/reperfusion injury: possible roles of the Akt/endothelial nitric oxide
      synthase-dependent pathway.

PMID- 22151695
TI  - The parasite that causes whirling disease, Myxobolus cerebralis, is genetically
      variable within and across spatial scales.
AB  - Understanding the genetic structure of parasite populations on the natural
      landscape can reveal important aspects of disease ecology and epidemiology and
      can indicate parasite dispersal across the landscape. Myxobolus cerebralis
      (Myxozoa: Myxosporea), the causative agent of whirling disease in the definitive
      host Tubifex tubifex, is native to Eurasia and has spread to more than 25 states
      in the USA. The small amounts of data available to date suggest that M.
      cerebralis has little genetic variability. We examined the genetic variability of
      parasites infecting the definitive host T. tubifex in the Madison River, MT, and
      also from other parts of North America and Europe. We cloned and sequenced 18S
      ribosomal DNA and the internal transcribed spacer-1 (ITS-1) gene. Five
      oligochaetes were examined for 18S and five for ITS-1, only one individual was
      examined for both genes. We found two different 18S rRNA haplotypes of M.
      cerebralis from five worms and both intra- and interworm genetic variation for
      ITS-1, which showed 16 different haplotypes from among 20 clones. Comparison of
      our sequences with those from other studies revealed M. cerebralis from MT was
      similar to the parasite collected from Alaska, Oregon, California, and Virginia
      in the USA and from Munich, Germany, based on 18S, whereas parasite sequences
      from West Virginia were very different. Combined with the high haplotype
      diversity of ITS-1 and uniqueness of ITS-1 haplotypes, our results show that M.
      cerebralis is more variable than previously thought and raises the possibility of
      multiple introductions of the parasite into North America.

PMID- 22151696
TI  - The association between major depression, health behaviors, and quality of life
      in adults with stroke.
AB  - AIM: The study aims to examine the association between major depression,
      healthcare behaviors, and quality of life indices among adults with stroke.
      METHODS: Data from 5869 participants with stroke in the 2006 Behavioral Risk
      Factor Surveillance Survey were examined. Multiple logistic regression was used
      to assess the independent association between depression status, self-care and
      preventive health behaviors, and quality of life indices, after accounting for
      relevant covariates. RESULTS: In multivariate models, individuals with major
      depression were less likely to engage in physical activity (odds ratio 0.41; 95%
      confidence interval 0.29, 0.56) than those without major depression. Women with
      major depression were also less likely to have received a mammogram in the past
      two-years (odds ratio 0.61; 95% confidence interval 0.40, 0.96 for women >= age
      40 and odds ratio 0.58; 95% confidence interval 0.36, 0.72 for women >= age 50)
      and a pap smear in the past three-years (odds ratio 0.40; 95% CI 0.22, 0.72). In
      comparisons of quality of life, individuals with major depression were less
      likely to perceive their health as excellent/very good/good (odds ratio 0.36; 95%
      confidence interval 0.25, 0.53), to report being satisfied with life (odds ratio
      0.13; 95% confidence interval 0.08, 0.20), and to report receiving needed social
      support (odds ratio 0.42; 95% confidence interval 0.28, 0.63). Individuals who
      were depressed were also more likely to report one or more poor physical and poor
      mental health days in the past 30 days (odds ratio 4.56; 95% confidence interval
      3.08, 6.76 and odds ratio 10.97; 95% confidence interval 7.75, 15.52,
      respectively). CONCLUSIONS: In adults with stroke, major depression is associated
      with decreased engagement in stroke-specific and gender-specific self-care and
      preventive health behaviors, as well as a broad range of quality of life indices.

PMID- 22151697
TI  - Assessment of dental trauma among cerebral palsy individuals in Udaipur city.
AB  - OBJECTIVE:   (i) To assess the prevalence of traumatic dental injuries (TDI) in
      individuals with cerebral palsy and its possible relationship with type of palsy
      at Udaipur city, Rajasthan, India. (ii) To assess the prevalence of
      temporomandibular joint symptoms in cerebral palsy individuals. MATERIALS AND
      METHODS:   The total sample comprised of 281 cerebral palsy individuals in the
      age group of 10-35 years. Clinical examination for dental trauma was performed on
      the basis of Andreasen & Andreasen classification (1994). Chi-square test,
      multiple logistic and stepwise linear regression analyses were carried out to
      find out the relationship between cerebral palsy individuals with different
      independent variables. RESULTS:   Findings of the study indicated that there was
      highest prevalence of TDI in cerebral palsy patients with hemiplegia (40.6%) (P =
      0.00). Stepwise and multiple logistic regression analyses showed that the best
      predictors for dental traumatic injuries was overjet and type of cerebral palsy.
      CONCLUSION:   It was concluded that hemiplegic cerebral palsy patients were most
      prone to TDI.

PMID- 22151698
TI  - Translating policy into practice: a case study in the secondary prevention of
      coronary heart disease.
AB  - BACKGROUND: This paper focuses on the relationships between health 'policy' as it
      is embodied in official documentation, and health 'practice' as reported and
      reflected on in the talk of policy-makers, health professionals and patients. The
      specific context for the study involves a comparison of policies relating to the
      secondary prevention of coronary heart disease (CHD) in the two jurisdictions of
      Ireland - involving as they do a predominantly state funded (National Health
      Service) system in the north and a mixed health-care economy in the south. The
      key question is to determine how the detail of health policy as contained in
      policy documents connects to and gets translated into practice and action.
      METHODS: The data sources for the study include relevant health-care policy
      documents (N=5) and progress reports (N=6) in the two Irish jurisdictions, and
      semi-structured interviews with a range of policy-makers (N=28), practice nurses
      (14), general practitioners (12) and patients (13) to explore their awareness of
      the documents' contents and how they saw the impact of 'policy' on primary care
      practice. RESULTS: The findings suggest that although strategic policy documents
      can be useful for highlighting and channelling attention to health issues that
      require concerted action, they have little impact on what either professionals or
      lay people do. CONCLUSION: To influence the latter and to encourage a systematic
      approach to the delivery of health care it seems likely that contractual
      arrangements - specifying tasks to be undertaken and methods for monitoring and
      reporting on activity - are required.

PMID- 22151699
TI  - Cachrys pungens Jan inhibits human melanoma cell proliferation through photo
      induced cytotoxic activity.
AB  - OBJECTIVE: To date, plants belonging to the genus Cachrys have not been amply
      studied. In the present study, aerial components of Cachrys pungens Jan from
      Italy, were examined to assess their free radical-scavenging and antioxidant
      activity, and their phototoxicity on A375 melanoma cells. In view of potential
      pharmaceutical applications, a relationship between antioxidant, phototoxic
      activities and polyphenolic composition has also been investigated. MATERIALS AND
      METHODS: Content of sterols, terpenes, fatty acids and coumarins was assessed by
      gas chromatography-mass spectrometry and GC. Total phenolic content was also
      determined. Antioxidant activity of the methanol extract and fractions of C.
      pungens Jan was assessed using DPPH scavenging assay and beta-carotene bleaching
      test. Plant phototoxicity was also investigated in this human tumour cell line
      (amelanotic melanoma). RESULTS:   Analysis of the chloroform extract was
      particularly interesting, as it led to identification of many coumarins, of which
      five were linear and one angular furanocoumarins. Methanol and ethyl acetate
      fractions exhibited substantial antioxidant activity. Moreover, chloroform
      extract and isolated coumarin fraction had strong phototoxic activity on UVA
      induced A375 cells after irradiation at UVA dose of 1.08 J/cm. CONCLUSIONS: Plant
      derived natural compounds are an important source for development of cancer
      fighting drugs. This study has demonstrated strong phototoxic activity of the
      coumarin fraction of C. pungens, a plant which, to our knowledge, has never been
      studied before. This investigation offers a new perspective for developing other
      formulations potentially useful in photodynamic therapy for treatment of non
      melanoma skin cancers as well as melanomas.

PMID- 22151701
TI  - Simple and efficient machine learning frameworks for identifying protein-protein
      interaction relevant articles and experimental methods used to study the
      interactions.
AB  - BACKGROUND: Protein-protein interaction (PPI) is an important biomedical
      phenomenon. Automatically detecting PPI-relevant articles and identifying methods
      that are used to study PPI are important text mining tasks. In this study, we
      have explored domain independent features to develop two open source machine
      learning frameworks. One performs binary classification to determine whether the
      given article is PPI relevant or not, named "Simple Classifier", and the other
      one maps the PPI relevant articles with corresponding interaction method nodes in
      a standardized PSI-MI (Proteomics Standards Initiative-Molecular Interactions)
      ontology, named "OntoNorm". RESULTS: We evaluated our system in the context of
      BioCreative challenge competition using the standardized data set. Our systems
      are amongst the top systems reported by the organizers, attaining 60.8% F1-score
      for identifying relevant documents, and 52.3% F1-score for mapping articles to
      interaction method ontology. CONCLUSION: Our results show that domain-independent
      machine learning frameworks can perform competitively well at the tasks of
      detecting PPI relevant articles and identifying the methods that were used to
      study the interaction in such articles. AVAILABILITY: Simple Classifier is
      available at http://sourceforge.net/p/simpleclassify/home/ and OntoNorm at
      http://sourceforge.net/p/ontonorm/home/.

PMID- 22151700
TI  - Diverse roles of G-protein coupled receptors in the regulation of
      neurohypophyseal hormone secretion.
AB  - The magnocellular neurones in the supraoptic nucleus project to the neural lobe
      and release vasopressin and oxytocin into the peripheral circulation, where they
      act on the kidney to promote fluid retention or stimulate smooth muscles in the
      vasculature, uterus and mammary glands to support blood pressure, promote
      parturition or induce milk let-down, respectively. Hormone release is regulated
      by complex afferent pathways carrying information about plasma osmolality, blood
      pressure and volume, cervical stretch, and suckling. These afferent pathways
      utilise a broad array of neurotransmitters and peptides that activate both ligand
      gated ion channels and G-protein coupled receptors (GPCRs). The ligand-gated ion
      channels induce rapid changes in membrane potential resulting in the generation
      of action potentials, initiation of exocytosis and the release of hormone into
      the periphery. By contrast, the GPCRs activate a host of diverse signalling
      cascades that modulate action potential firing and regulate other cellular
      functions required to support hormone release (e.g. hormone synthesis,
      processing, packaging and trafficking). The diversity of these actions is
      critical for integration of the distinct regulatory signals into a response
      appropriate for maintaining homeostasis. This review describes several diverse
      roles of GPCRs in magnocellular neurones, focusing primarily on adrenergic,
      purinergic and peptidergic (neurokinin and angiotensin) receptors.

PMID- 22151702
TI  - Mosaic SCN1A mutations in familial partial epilepsy with antecedent febrile
      seizures.
AB  - SCN1A is the most relevant epilepsy gene. Mutations of SCN1A generate phenotypes
      ranging from the extremely severe form of Dravet syndrome (DS) to a mild form of
      generalized epilepsy with febrile seizures plus (GEFS+). Mosaic SCN1A mutations
      have been identified in rare familial DS. It is suspected that mosaic mutations
      of SCN1A may cause other types of familial epilepsies with febrile seizures (FS),
      which are more common clinically. Thus, we screened SCN1A mutations in 13
      families with partial epilepsy with antecedent febrile seizures (PEFS+) using
      denaturing high-performance liquid chromatography and sequencing. The level of
      mosaicism was further quantified by pyrosequencing. Two missense SCN1A mutations
      with mosaic origin were identified in two unrelated families, accounting for
      15.4% (2/13) of the PEFS+ families tested. One of the mosaic carriers with ~25.0%
      mutation of c.5768A>G/p.Q1923R had experienced simple FS; another with ~12.5%
      mutation of c.4847T>C/p.I1616T was asymptomatic. Their heterozygous children had
      PEFS+. Recurrent transmission occurred in both families, as noted in most of the
      families with germline mosaicism reported previously. The two mosaic mutations
      identified in this study are less destructive missense, compared with the more
      destructive truncating and splice-site mutations identified in the majority of
      previous studies. This is the first report of mosaic SCN1A mutations in families
      with probands that do not exhibit DS, but manifest only a milder phenotype.
      Therefore, such families with mild cases should be approached with caution in
      genetic counseling and the possibility of mosaicism origin associated with high
      recurrence risk should be excluded.

PMID- 22151704
TI  - Multilocus coalescent analysis of haemoglobin differentiation between low- and
      high-altitude populations of crested ducks (Lophonetta specularioides).
AB  - Hypoxia is a key factor determining survival, and haemoglobins are targets of
      selection in species native to high-altitude regions. We studied population
      genetic structure and evaluated evidence for local adaptation in the crested duck
      (Lophonetta specularioides). Differentiation, gene flow and time since divergence
      between highland and lowland populations were assessed for three haemoglobin
      genes (alpha(A) , alpha(D) , beta(A) ) and compared to seven reference loci (six
      autosomal introns and mtDNA). Four derived amino acid replacements were found in
      the globin genes that had elevated Phi(ST)  values between the Andean highlands
      and Patagonian lowlands. A single beta(A) -globin polymorphism at a site known to
      influence O(2)  affinity was fixed for different alleles in the two populations,
      whereas three alpha(A) - and alpha(D) -globin polymorphisms exhibited high
      heterozygosity in the highlands but not in the lowlands. Coalescent analyses
      supported restricted gene flow for haemoglobin alleles and mitochondrial DNA but
      nonzero gene flow for the introns. Simulating genetic data under a drift
      migration model of selective neutrality, the beta(A) -globin fell outside the 95%
      confidence limit of simulated data, suggesting that directional selection is
      maintaining different variants in the contrasting elevational environments,
      thereby restricting migration of beta(A) -globin alleles. The alpha(A) - and
      alpha(D) -globins, by contrast, did not differ from the simulated values,
      suggesting that variants in these genes are either selectively neutral, or that
      the effects of selection could not be differentiated from background levels of
      population structure and linkage disequilibrium. This study illustrates the
      combined effects of selection and population history on inferring levels of
      population divergence for a species distributed across an altitudinal gradient in
      which selection for hypoxia resistance has likely played an important role.

PMID- 22151705
TI  - Remembering a dear friend and colleague: john oakley, MD january 11, 1946-april
      17, 2006.

PMID- 22151703
TI  - Malaria parasite pre-erythrocytic infection: preparation meets opportunity.
AB  - For those stricken with malaria, the classic clinical symptoms are caused by the
      parasite's cyclic infection of red blood cells. However, this erythrocytic phase
      of the parasite's life cycle initiates from an asymptomatic pre-erythrocytic
      phase: the injection of sporozoites via the bite of a parasite-carrying
      Anopheline mosquito, and the ensuing infection of the liver. With the increased
      capabilities of studying liver stages in mice, much progress has been made
      elucidating the cellular and molecular basis of the parasite's progression
      through this bottleneck of its life cycle. Here we review relevant findings on
      how sporozoites prepare for infection of the liver and factors crucial to liver
      stage development as well as key host/parasite interactions.

PMID- 22151706
TI  - Prevention of mechanical failures in implanted spinal cord stimulation systems.
AB  - Introduction.  Spinal cord stimulation (SCS) is an effective procedure for the
      treatment of neuropathic extremity pain, with success rates approaching 70%.
      However, mechanical failures, including breakage and migration, can significantly
      limit the long-term effectiveness of SCS. A systematic analysis of surgical
      techniques was undertaken by a consensus group, coupled with extensive in vivo
      and in vitro biomechanical testing of system components. Methods.  A computer
      model based on morphometric data was used to predict movement in a standard SCS
      system between an anchored lead and pulse generator placed in various locations.
      These displacements were then used to determine a realistic range of forces
      exerted on components of the SCS system. Laboratory fixtures were constructed to
      subject leads and anchors to repetitive stresses until failure occurred. An in
      vivo sheep model also was used to determine system compliances and failure
      thresholds in a biologically realistic setting. A panel of experienced implanters
      then interpreted the results and related them to clinical observations. Results. 
      Use of a soft silastic anchor pushed through the fascia to provide a larger bend
      radius for the lead was associated with a time to failure 65 times longer than an
      anchored but unsupported lead. In addition, failures of surgical paddle leads
      occurred when used with an anchor, whereas without an anchor, no failures
      occurred to 1 million cycles. Based on these findings, the panel recommended a
      paramedian approach, abdominal pulse generator placement, maximizing bend radius
      by pushing the anchor through the fascia, and anchoring of the extension
      connector near the lead anchor. Discussion.  Several factors are important in
      longevity of SCS systems. We discovered that technical factors can make a large
      difference in SCS reliability and that strict attention to these "best practices"
      will provide the best chance for maintaining the integrity of SCS systems over
      the long term.

PMID- 22151707
TI  - Transverse tripolar spinal cord stimulation: results of an international
      multicenter study.
AB  - Experienced neurosurgeons at eight spinal cord stimulation centers in the United
      States, Canada, and Europe participated in a study from 1997 to 2000
      investigating the safety, performance, and efficacy of a Transverse Tripolar
      Stimulation (TTS) system invented at the University of Twente, the Netherlands.
      This device was proposed to improve the ability of spinal cord stimulation to
      adequately overlap paresthesia to perceived areas of pain. Fifty-six patients
      with chronic, intractable neuropathic pain of the trunk and/or limbs more than
      three months' duration (average 105 months) were enrolled with follow-up periods
      at 4, 12, 26, and 52 weeks. All patients had a new paddle-type lead implanted
      with four electrodes, three of them aligned in a row perpendicular to the cord.
      Fifteen of these patients did not undergo permanent implantation. Of the 41
      patients internalized, 20 patients chose conventional programming using an
      implanted pulse generator to drive four electrodes, while 21 patients chose a
      tripole stimulation system, which used radiofrequency power and signal
      transmission and an implanted dual-channel receiver to drive three electrodes
      using simultaneous pulses of independently variable amplitude. On average, the
      visual analog scale scores dropped more for patients with TTS systems (32%) than
      for conventional polarity systems (16%). Conventional polarity systems were using
      higher frequencies on average, while usage range was similar. Most impressive was
      the well-controlled "steering" of the paresthesias according to the dermatomal
      topography of the dorsal columns when using the TTS-balanced pulse driver. The
      most common complication was lead migration. While the transverse stimulation
      system produced acceptable outcomes for overall pain relief, an analysis of
      individual pain patterns suggests that it behaves like spinal cord stimulation in
      general with the best control of extremity neuropathic pain. This transverse
      tripole lead and driving system introduced the concept of electrical field
      steering by selective recruitment of axonal nerve fiber tracts in the dorsal
      columns.

PMID- 22151708
TI  - Vagus nerve stimulation therapy system: in vitro evaluation of magnetic resonance
      imaging-related heating and function at 1.5 and 3 tesla.
AB  - Objectives.  To evaluate magnetic resonance imaging-related (MRI-related) heating
      for the VNS Therapy System at 1.5 and 3 tesla (T) using various device
      configurations and MRI conditions and to assess device function before and after
      MRI. Methods.  The VNS Therapy System (pulse generator, Model 102; leads Models
      300 and 302; Cyberonics, Inc., Houston, Tex, USA) underwent assessment of MRI
      related heating at 1.5 and 3 T using different positioning configurations, leads,
      transmit radiofrequency (RF) coils (body and head), RF power levels, and scans on
      different body regions. The function of the VNS Therapy System was evaluated
      before and after scanning. Results.  At 1.5 T using a transmit RF body coil,
      excessive temperature changes were associated with scans of the C-spine/shoulder
      (+11.5 degrees C, complete system; +29.5 degrees C, lead without pulse
      generator). The lowest temperature change occurred for the scan of the L-spine.
      At 1.5 T using a transmit/receive RF head coil, temperature changes did not
      exceed +0.2 degrees C under the conditions studied. At 3 T using a transmit RF
      body coil, the highest temperature change occurred with the scan of the C
      spine/shoulder (+14.5 degrees C) with the lead configured with no strain relief
      loops at the vagus nerve. MRI performed using various conditions at 1.5 and 3 T
      produced no significant alterations in the function of the VNS Therapy System.
      Conclusions.  MRI-related heating was characterized for a variety of scenarios,
      identifying unsafe as well as safe conditions. Device function was unaffected by
      MRI procedures at 1.5 and 3 T. By following specific conditions, safety
      guidelines for the VNS Therapy System may be expanded beyond those currently
      indicated by the manufacturer.

PMID- 22151709
TI  - Heart rate control via vagus nerve stimulation.
AB  - Objectives.  There is ample and well-established evidence that direct electrical
      stimulation of the vagus nerve can change heart rate in animals and humans. Since
      tachyarrhythmias cannot always be controlled through medication, we sought, in
      this pilot study, to elucidate whether a clinical implantable lead system that is
      used in cervical vagus nerve stimulation therapy (VNS therapy) also can be used
      for control of heart rate, and tachycardia in particular. Materials and Methods. 
      Experiments were carried out in three pigs (weight 21-26 kg) under general
      anesthesia. The right and left vagus nerves in the neck region were exposed by
      dissection, and bipolar, multiturn, helical, silicone leads were wrapped around
      the vagus nerves. Stimulation was applied by an external device with
      multivariable settings: frequency 10-100 Hz, pulse duration 100-700 usec; delay 0
      0.5 msec; current 0.5-14 mA. Measurements were performed under normal sinus
      rhythm (RR-interval 501 +/- 30 msec) and during isoprenaline-induced tachycardia
      (RR-interval 284 +/- 11 msec). Results.  VNS, under optimal pacing conditions
      (100 Hz; 5 mA; 0.2 msec; 70 msec delay), in an electrocardiogram-triggered (ECG
      triggered) pacing mode, increased RR-intervals by approximately 40%, irrespective
      of the duration of the RR-interval preceding VNS. The maximum effect on heart
      rate was established within approximately 5 sec after the onset of stimulation
      and was reversible and reproducible. No differences were found between
      stimulation of the right or left vagus nerve. Conclusion.  VNS can be used
      effectively and rapidly to decrease heart rate, in acute settings, when connected
      to an external pacing system. Future devices that are fully implantable may be
      used for nonpharmacological treatment of illnesses in which tachycardia results
      in deterioration of cardiac function.

PMID- 22151710
TI  - Bilateral Implantation of Centromedian-Parafascicularis Complex and GPi: A New
      Combination of Unconventional Targets for Deep Brain Stimulation in Severe
      Parkinson Disease.
AB  - Objectives.  Traditional deep brain stimulation (DBS) at the subthalamic nucleus
      (STN) has proved to be efficacious on core Parkinsonian symptoms. However, very
      disabling l-dopa-induced abnormal involuntary movements (AIMs) and axial signs
      are slightly affected, suggesting that we target less conventional targets. Our
      candidates for DBS were the globus pallidus internus (GPi) plus the intralaminar
      thalamic complex (Pf or CM), given its extensive functional links with basal
      ganglia nuclei. Materials and Methods.  The routine utilization of our innovative
      stereotactic apparatus allows us to implant, at the same time, both the CM-Pf
      complex together with the GPi in six Parkinson disease patients. Both
      intraoperative and postoperative neurophysiologic assessments helped us recognize
      functional subregions while optimizing implantation of electrodes. Unified
      Parkinson disease rating scale (UPDRS) motor scores, AIMs, and freezing were
      carefully blindly evaluated for each condition. Results.  A significant
      amelioration of UPDRS scores was achieved by simultaneous activation of both
      targets. CM-Pf activation was only slightly effective in reducing rigidity and
      akinesia, but more efficacious on freezing. Not surprisingly, AIMs were
      peculiarly decreased by the activation of the permanent electro-catheter in the
      posteroventral GPi. Conclusions.  These findings confirm that, in selected
      patients, it is conceivable to target structures other than the conventional STN
      in order to maximize clinical benefit.

PMID- 22151711
TI  - Sacral nerve stimulation with percutaneous dorsal transforamenal approach in
      treatment of isolated pelvic pain syndromes.
AB  - Objectives.  The aim of the study was to test the effectiveness of sacral nerve
      stimulation (SNS) performed by a transforamenal approach in patients with
      isolated chronic intractable pelvic pain. Materials.  Sevenpatients with
      intractable pelvic pain underwent implantation of self-anchoring leads by way of
      the dorsal S3 foramen in four cases and of the dorsal S4 foramen in three cases.
      Patients with pain improvement > 50% underwent sacral nerve root stimulation
      device implantation. SNS therapeutic efficacy was measured using a visual analog
      scale (VAS) and its effects on quality of life (QoL) using the SF-36 scale.
      Results.  During test stimulation five patients had significant and permanent
      pain relief and subsequently underwent implantation of a permanent device. VAS
      score improvement was evident in these patients and remained unchanged at 3, 6,
      and 12 months (median 8 months); SF-36 QoL questionnaire also revealed
      significant improvement in many domains of QoL including all the four physical
      domains and three of the four mental domains. There were three complications in
      our seven patients: one lead fracture, one lead displacement in the presacral
      space, and one patient who developed pain at the implantable pulse generator
      site. Conclusions.  Transforamenal SNS is effective in relieving isolated pelvic
      pain but a high complication rate was found.

PMID- 22151712
TI  - Electrical stimulation using implantable radiofrequency microstimulators to
      relieve pain associated with shoulder subluxation in chronic hemiplegic stroke.
AB  - Objective.  To evaluate the ability to relieve shoulder pain by implanting
      ceramic-case versions of radiofrequency microstimulators (RFM) in paralyzed
      shoulder muscles. Materials and Methods.  A 66-year-old man, who had left-sided
      chronic hemiplegia due to a stroke five years previously, had developed shoulder
      subluxation resulting in pain. Two RFM devices were implanted, one next to the
      axillary nerve and one at the motor point of the middle deltoid muscle.
      Electrical stimulation at both sites was commenced two weeks after implantation
      for a six-month period. Our evaluation of the effectiveness of the RFM devices
      has been by measuring pain (using the visual analog scale: VAS), range of motion
      at the shoulder, strength of the deltoid muscle, degree of shoulder subluxation,
      and muscle atrophy. Following commencement of stimulation, follow-up evaluations
      were performed at one, two, three, four, and six weeks, three and six months, and
      after six months of no stimulation. Results.  During the treatment period of six
      months of stimulation, the patient's pain had reduced from 70 to 0 on the VAS. At
      six months after completion of the treatment, pain relief and effective evoked
      muscle contraction have remained. Conclusion.  Although these results suggest
      that the feasibility of using RFM devices implanted both epineurally to the
      axillary nerve and next to the muscle motor point in this one patient, to relieve
      pain and elicit contraction, further investigation is needed to demonstrate the
      clinical feasibility of using RFMs for treating poststroke shoulder pain.

PMID- 22151713
TI  - Quantitative sensory testing in patients with chronic unilateral radicular
      neuropathic pain and active spinal cord stimulation.
AB  - Objectives.  Spinal cord stimulation (SCS) is an effective treatment option for
      chronic radicular neuropathic pain syndromes. This prospective study was
      performed to examine the peripheral effects of SCS on sensation using
      quantitative sensory testing (QST). Materials and Methods.  We measured two
      consecutive QST measurements for thermal, tactile-static, tactile-dynamic,
      vibratory, and pain sensation of the lower limbs in seven patients with chronic
      unilateral radicular neuropathic pain who underwent SCS implantation for their
      pain. Measurements were performed when SCS was turned off and once again during
      SCS and subsequent reduced pain levels. Results.  Baseline QST demonstrated
      significantly increased thresholds for tactile and warm and cold detection in the
      pain area. With SCS active, a significant reduction of the cold and warm
      perception and mechanical detection thresholds was found on the painful side (p <
      0.01). Although not significant (p > 0.01), altered sensory thresholds with
      active SCS also were found at the healthy side where no paresthesias were felt.
      Conclusion.  SCS leads to bilateral subclinical effects even if the evoked
      paresthesias are only unilateral. Pain perception thresholds are not altered with
      therapeutic SCS.

PMID- 22151714
TI  - Factors affecting the use of patient survey data for quality improvement in the
      Veterans Health Administration.
AB  - BACKGROUND: Little is known about how to use patient feedback to improve
      experiences of health care. The Veterans Health Administration (VA) conducts
      regular patient surveys that have indicated improved care experiences over the
      past decade. The goal of this study was to assess factors that were barriers to,
      or promoters of, efforts to improve care experiences in VA facilities. METHODS:
      We conducted case studies at two VA facilities, one with stable high scores on
      inpatient reports of emotional support between 2002 and 2006, and one with stable
      low scores over the same period. A semi-structured interview was used to gather
      information from staff who worked with patient survey data at the study
      facilities. Data were analyzed using a previously developed qualitative framework
      describing organizational, professional and data-related barriers and promoters
      to data use. RESULTS: Respondents reported more promoters than barriers to using
      survey data, and particularly support for improvement efforts. Themes included
      developing patient-centered cultures, quality improvement structures such as
      regular data review, and training staff in patient-centered behaviors. The
      influence of incentives, the role of nursing leadership, and triangulating survey
      data with other data on patients' views also emerged as important. It was easier
      to collect data on current organization and practice than those in the past and
      this made it difficult to deduce which factors might influence differing facility
      performance. CONCLUSIONS: Interviews with VA staff provided promising examples of
      how systematic processes for using survey data can be implemented as part of
      wider quality improvement efforts. However, prospective studies are needed to
      identify the most effective strategies for using patient feedback to improve
      specific aspects of patient-centered care.

PMID- 22151716
TI  - Preface.

PMID- 22151715
TI  - Efficient algorithms for reconstructing gene content by co-evolution.
AB  - BACKGROUND: In a previous study we demonstrated that co-evolutionary information
      can be utilized for improving the accuracy of ancestral gene content
      reconstruction. To this end, we defined a new computational problem, the
      Ancestral Co-Evolutionary (ACE) problem, and developed algorithms for solving it.
      RESULTS: In the current paper we generalize our previous study in various ways.
      First, we describe new efficient computational approaches for solving the ACE
      problem. The new approaches are based on reductions to classical methods such as
      linear programming relaxation, quadratic programming, and min-cut. Second, we
      report new computational hardness results related to the ACE, including practical
      cases where it can be solved in polynomial time.Third, we generalize the ACE
      problem and demonstrate how our approach can be used for inferring parts of the
      genomes of non-ancestral organisms. To this end, we describe a heuristic for
      finding the portion of the genome ('dominant set') that can be used to
      reconstruct the rest of the genome with the lowest error rate. This heuristic
      utilizes both evolutionary information and co-evolutionary information.We
      implemented these algorithms on a large input of the ACE problem (95 unicellular
      organisms, 4,873 protein families, and 10, 576 of co-evolutionary relations),
      demonstrating that some of these algorithms can outperform the algorithm used in
      our previous study. In addition, we show that based on our approach a 'dominant
      set' cab be used reconstruct a major fraction of a genome (up to 79%) with
      relatively low error-rate (e.g. 0.11). We find that the 'dominant set' tends to
      include metabolic and regulatory genes, with high evolutionary rate, and low
      protein abundance and number of protein-protein interactions. CONCLUSIONS: The
      ACE problem can be efficiently extended for inferring the genomes of organisms
      that exist today. In addition, it may be solved in polynomial time in many
      practical cases. Metabolic and regulatory genes were found to be the most
      important groups of genes necessary for reconstructing gene content of an
      organism based on other related genomes.

PMID- 22151717
TI  - Abrupt intrathecal baclofen withdrawal: management of potentially life
      threatening sequelae.

PMID- 22151718
TI  - Clinical and therapeutic applications of neuromuscular stimulation: a review of
      current use and speculation into future developments.
AB  - In this paper we present an overview of current research into clinical and
      therapeutic applications of electrical neuromuscular stimulation (NMS). As this
      is now such a huge subject we have focused our attention on the therapeutic
      rather than orthotic uses of stimulation and limited the field almost exclusively
      to upper limb applications in hemiplegia. The evidence that NMS influences motor
      re-learning and how this may be measured is discussed. We have identified the
      following as the three most important unresolved issues: 1) an understanding of
      how NMS modifies the interactions within the nervous system, 2) clinical
      effectiveness of NMS, and 3) inexpensive, simple to insert and reliable
      controllable implanted systems. We discuss recent research aimed at resolving
      these issues and based on this we make some suggestions for future research. To
      resolve these issues we propose: 1) neurophysiologic research into the mechanism
      through which NMS interacts with the nervous system; 2) large multicenter
      randomized controlled trials using rigorous methodology that compare different
      applications of NMs; 3) continued technical development that is closely linked to
      clinical applications.

PMID- 22151719
TI  - Functional electrical stimulation for control of internal organ function.
AB  - This paper discusses the use of electrical stimulation for cardiac assist and
      control of bladder and bowel. It describes the state of the art, what progress
      there will be in the coming 10 years and what problems need to be solved in order
      to make that progress. The paper speculates that within 10 years, there will be
      patients whose cardiac function is augmented by the pumping function of skeletal
      muscle assist devices, and furthermore that within 10 years new implantable
      devices will be available to improve both bladder and bowel emptying by
      electrical stimulation. Yet another implantable device may become available which
      allows treatment of detrusor hyperreflexia without the need for a dorsal sacral
      rhizotomy.

PMID- 22151720
TI  - Command and control interfaces for advanced neuroprosthetic applications.
AB  - Command and control interfaces permit the intention and situation of the user to
      influence the operation of the neural prosthesis. The wishes of the user are
      communicated via command interfaces to the neural prosthesis and the situation of
      the user by feedback control interfaces. Both these interfaces have been reviewed
      separately and are discussed in light of the current state of the art and
      projections for the future. It is apparent that as system functional complexity
      increases, the need for simpler command interfaces will increase. Such systems
      will demand more information to function effectively in order not to unreasonably
      increase user attention overhead. This will increase the need for bioelectric and
      biomechanical signals in a comprehensible form via elegant feedback control
      interfaces. Implementing such systems will also increase the computational demand
      on such neural prostheses.

PMID- 22151721
TI  - Current status and future prospects for upper and lower extremity motor system
      neuroprostheses.
AB  - This paper reviews the current state of the art and identifies the major
      challenges facing the future development and clinical application of
      neuroprostheses to provide limb movement. It gives insight into the current
      status of functional electrical stimulation (FES) for motor control, identifies
      problems, and proposes possible directions of development in cervical cord
      injury, thoracic spinal cord injury, and stroke. For upper extremity function,
      existing clinical applications are covered, major problems are identified, and
      possible future trends are highlighted. The discussion on lower extremity
      applications describes current and possible future solutions of the major
      impediments to the development of FES systems for individuals with paraplegia
      after spinal cord injury and surface and implantable setups for stroke survivors
      with hemiplegia. Particular attention is given to sensor issues and requirements
      for walking with FES after stroke.

PMID- 22151722
TI  - Using mathematical models and advanced control systems techniques to enhance
      neuroprosthesis function.
AB  - Systems that use electrical stimulation to activate paralyzed muscles, called
      "neuroprostheses", have restored important functional capabilities to many people
      with neurologic disorders such as spinal cord injury or stroke. However, the
      clinical benefits derived from neuroprostheses have been limited by the quality
      of control of posture and movement that has been achieved. Over the past few
      decades, engineers have used mathematical models and control systems technology
      to develop functional neuromuscular stimulation (FNS) control systems that show
      promise in the laboratory, but these have not yet been incorporated into
      practical solutions for clinical problems. This article briefly reviews several
      of the complicating factors in controlling FNS systems and describes the
      potential roles of biomechanical modeling and advanced control system technology.
      Three important challenges in FNS control systems research and development are
      identified: 1) to obtain an improved understanding of the biomechanical system
      that we are trying to control and how it is controlled by the intact neural
      system, 2) to develop new control system technology with a particular focus on
      strategies that mimic those used by biologic systems, and 3) to integrate the
      knowledge and technologies into useful systems that meet the needs of
      neuroprosthesis users. The outlook for the future includes many interesting
      problems; yet more importantly, it includes relevant clinical benefits to be
      gained through the application of biomechanical models and advanced control
      systems techniques in neuroprostheses.

PMID- 22151724
TI  - Reply to letter to the editor (2000;3:209).

PMID- 22151723
TI  - Implantable FES Stimulation Systems: What is Needed?
AB  - Since their initial development, the performance gains in functional electrical
      stimulation (FES) systems have been modest. Conceptually, the replacement of
      normal neural function by artificial electronic systems is attractive,
      considering the continued technologic advancements in electronics, communication,
      and control. It is likely that efficacious FES systems will require complete
      implantation and activation of large numbers of motor units. One approach is to
      develop a neural interface that has a one-to-one relationship between stimulating
      electrodes and lower motor neurons. While technology may offer solutions to the
      design of miniaturized implantable stimulators, the high-density neural interface
      remains more elusive. During the past 20 years, research in the stimulation of
      peripheral motor systems has been primarily constrained by progress in two areas
      of research: strategies for the control of paralyzed muscle and sophistication of
      implantable stimulation systems. Often, a debate concerning which of these two
      areas is a "critical path" element yields no strategic ideas. It has been stated
      that a need must be demonstrated for a specific number of electrode channels
      before it is warranted to invest effort into the engineering of implantable
      systems that are capable of driving large numbers of electrodes. Indeed it is a
      logical approach to problem solving that the need should drive the development of
      function. Even study sections, in review of FES grant applications, often resort
      to this logic. In our opinion, when applied to FES, this argument is often
      fallacious and ignores the reality that research frequently requires that a
      threshold of experimental methodology be reached before any meaningful work can
      be accomplished. Practical trials of stimulation control strategies, long-term
      patient acceptance, and achievable function for FES systems cannot begin without
      the capability of stimulation. And, in order to determine whether or not
      stimulating large numbers of muscle groups can lead to more natural control of
      movement, suitable stimulation hardware must first exist, and be reliable. In the
      specific case of lower extremity FES research, it is likely that without a
      quantum advance in technologic capabilities, the practical utility of FES systems
      will continue to only be marginally close to normal function. To reach the level
      of being considered a routine treatment for spinal cord injury, FES systems
      should be able to offer improved functionality, ease of use, and near-equal
      reliability, compared to wheelchairs. At present, no FES systems attain this
      combination. The functional reliability of FES systems must approach 100%. As a
      trivial example, consider that for a standing, or walking, system, the
      perspectives of bioengineers and users may be quite different. While an engineer
      might be pleased to design a system that functions, as intended, 99% of the time,
      if a user falls down 1 time out of every 100, this is likely to be unacceptable.
      The minimal threshold of functional utility for FES systems is unclear, and will
      not be addressed here. Rather, we consider the issues of what features and
      capabilities are desirable for next generation implantable systems, and to what
      degree these desires approach engineering feasibility.

PMID- 22151725
TI  - Interactions between tumor cells and microenvironment in breast cancer: a new
      opportunity for targeted therapy.
AB  - Breast cancer remains the leading cause of morbidity and second-leading cause of
      death in women. Despite efforts to uncover new targeted therapies, a vast number
      of women die due to refractory or recurrent breast tumors. Most breast cancer
      studies have focused on the intrinsic characteristics of breast tumor cells,
      including altered growth, proliferation, and metabolism. However, emerging
      research suggests that the tumor microenvironment can substantially affect
      relapse rates and therapeutic responses. In this review, we discuss the
      interactions between the tumor and microenvironment in breast cancer, with regard
      to mutational profiles and altered metabolism that could serve as potential
      therapeutic targets. We also describe current technologies available to study
      these interactions.

PMID- 22151726
TI  - Human papillomavirus L2 facilitates viral escape from late endosomes via sorting
      nexin 17.
AB  - The human papillomavirus (HPV) L2 capsid protein plays an essential role during
      the early stages of viral infection, but the molecular mechanisms underlying its
      mode of action remain obscure. Using a proteomic approach, we have identified the
      adaptor protein, sorting nexin 17 (SNX17) as a strong interacting partner of HPV
      L2. This interaction occurs through a highly conserved SNX17 consensus binding
      motif, which is present in the majority of HPV L2 proteins analysed. Using
      mutants of L2 defective for SNX17 interaction, or siRNA ablation of SNX17
      expression, we demonstrate that the interaction between L2 and SNX17 is essential
      for viral infection. Furthermore, loss of the L2-SNX17 interaction results in
      enhanced turnover of the L2 protein and decreased stability of the viral capsids,
      and concomitantly, there is a dramatic decrease in the efficiency with which
      viral genomes transit to the nucleus. Indeed, using a range of endosomal and
      lysosomal markers, we show that capsids defective in their capacity to bind SNX17
      transit much more rapidly to the lysosomal compartment. These results demonstrate
      that the L2-SNX17 interaction is essential for viral infection and facilitates
      the escape of the L2-DNA complex from the late endosomal/lysosomal compartments.

PMID- 22151727
TI  - Activating knowledge for patient safety practices: a Canadian academic-policy
      partnership.
AB  - BACKGROUND: Over the past decade, the need for healthcare delivery systems to
      identify and address patient safety issues has been propelled to the forefront. A
      Canadian survey, for example, demonstrated patient safety to be a major concern
      of frontline nurses (Nicklin & McVeety 2002). Three crucial patient safety
      elements, current knowledge, resources, and context of care have been identified
      by the World Health Organization (WHO 2009). To develop strategies to respond to
      the scope and mandate of the WHO report within the Canadian context, a pan
      Canadian academic-policy partnership has been established. APPROACH: This newly
      formed Pan-Canadian Partnership, the Queen's Joanna Briggs Collaboration for
      Patient Safety (referred throughout as "QJBC" or "the Partnership"), includes the
      Queen's University School of Nursing, Accreditation Canada, the Canadian Patient
      Safety Institute (CPSI), the Canadian Institutes of Health Research, and is
      supported by an active and committed advisory council representing over 10
      national organizations representing all sectors of the health continuum,
      including patients/families advocacy groups, professional associations, and other
      bodies. This unique partnership is designed to provide timely, focused support
      from academia to the front line of patient safety. QJBC has adopted an
      "integrated knowledge translation" approach to identify and respond to patient
      safety priorities and to ensure active engagement with stakeholders in producing
      and using available knowledge. Synthesis of evidence and guideline adaptation
      methodologies are employed to access quantitative and qualitative evidence
      relevant to pertinent patient safety questions and subsequently, to respond to
      issues of feasibility, meaningfulness, appropriateness/acceptability, and
      effectiveness. SUMMARY: This paper describes the conceptual grounding of the
      Partnership, its proposed methods, and its plan for action. It is hoped that our
      journey may provide some guidance to others as they develop patient safety models
      within their own arenas.

PMID- 22151728
TI  - The impact of pre-treatment weight-loss expectations on weight loss, weight
      regain, and attrition in people who are overweight and obese: a systematic review
      of the literature.
AB  - PURPOSE:  Research exploring the relationships between initial weight-loss
      expectations with actual outcome in terms of weight loss, weight regain, and
      attrition/attendance suggests contradictory findings. The purpose of this review
      was to collate research exploring the impact of weight-loss expectations on
      weight loss, weight regain, and attendance/attrition. It was hoped this would
      further the current understanding of the relationship between expectations and
      outcome. METHODS:  PsychInfo, Medline, and Web of Science were systematically
      searched and 13 relevant papers were identified. To be included for review,
      studies had to assess and analyse weight-related expectations; distinguish
      between higher and lower expectations; include participants who were aged over 18
      and attempting to lose weight; be published within a peer-reviewed journal
      between 1990 and 2010. Findings were analysed qualitatively. RESULTS:  Findings
      were largely unclear. The relationship between expectations and weight loss
      appears to change with time, whilst the findings from studies looking at weight
      regain suggest that there is no association. The relationship between
      expectations with attendance/attrition is also unclear. CONCLUSIONS:  Through
      reviewing literature regarding the relationships between expectations with
      various outcomes, a number of discrepancies emerged. Exploration of these
      discrepancies enabled an understanding to be developed of the complex
      relationship between expectations and weight-loss treatment outcome. The
      importance of the terminology used and the ways in which expectations are
      assessed is discussed and future areas of research are suggested.

PMID- 22151729
TI  - A prospective, open-label, multicenter study to assess the efficacy of spinal
      cord stimulation and identify patients who would benefit.
AB  - OBJECTIVE:   To identify patients likely to benefit from spinal cord stimulation
      (SCS). MATERIALS AND METHODS:   This multicenter, prospective, open-label study
      included medical centers experienced in SCS therapy, carried out in 13 physicians
      in seven centers. We recruited 55 patients with complex regional pain syndrome,
      failed back surgery syndrome, or peripheral vascular disease. Neurostimulators
      were implanted in 34 patients found to respond to SCS in a preliminary test, who
      were then followed for six months. Thirty-four patients scored their pain on a
      visual analog scale (VAS) and completed the EuroQol-5D questionnaire before and
      after test stimulation and after one and six months. RESULTS:   During test
      stimulation, the mean VAS and quality of life (QOL) scores improved from 74.0 to
      23.4 and from 0.430 to 0.664, respectively, in the 34 patients. At six months,
      the mean VAS score was 29.7 in 29 patients and the mean QOL score was 0.661 in 31
      patients. CONCLUSION:   SCS may improve pain management and QOL.

PMID- 22151731
TI  - Small artery structure and function: a dual interaction with many players.

PMID- 22151733
TI  - Primary clear cell sarcoma of humerus: case report.
AB  - We report a case of primary clear cell sarcoma occurring in the humerus. A 20
      year old girl was referred to our hospital two years ago with painless swelling
      of the soft tissue surrounding the proximal right humerus. The conventional
      radiographic image showed an ill-defined, aggressive, osteolytic lesion
      associated with a partial cortical defect of the proximal right humerus. Magnetic
      resonance imaging found an irregularly shaped extraosseous mass extending from
      the proximal shaft of the right humerus, penetrating through the destroyed bone
      and invading the biceps brachii. After preoperative chemotherapy, a total tumor
      resection, internal fixation and bone cement implantation were performed.
      Histological studies of the resected tumor found that fibrous septa divided into
      well-defined nests and polygonal and fusiform cells with clear cytoplasm.
      Immunohistochemical studies demonstrated strong positive cytoplasmic staining
      with S-100 and scattered positivity with HMB-45. These findings led to a final,
      definitive diagnosis of clear cell sarcoma of the humerus. After routine
      postoperative chemotherapy, a 2-year follow-up showed no metastasis. Our findings
      in this report point out that primary clear cell sarcoma can originate from
      within the humerus and that limb salvage surgery can obtain a good result.

PMID- 22151734
TI  - Recommendations for the treatment of nail psoriasis in patients with moderate to
      severe psoriasis: a dermatology expert group consensus.
AB  - BACKGROUND: Nail involvement is common in psoriasis patients and is often
      associated with severe disease. Patients with nail psoriasis experience pain,
      functional impairment and social stigma, with significant restriction of daily
      activities and quality of life. However, nail psoriasis often goes untreated, as
      many physicians believe it is difficult to treat, despite the availability of
      effective treatment options. Clinical data and guidelines for managing and
      treating psoriasis patients with both skin and nail symptoms are limited.
      OBJECTIVE: To prepare recommendations for the management and treatment of
      patients with moderate to severe psoriasis with nail involvement. METHODS: A
      collaborative Delphi survey was used to obtain consensus on current practice in
      the management of nail disease in patients with moderate to severe psoriasis from
      an expert panel of 11 dermatologists from Europe and Canada with substantial
      clinical expertise in managing these patients. Agreement was defined utilizing a
      Likert scale of 1-9. Consensus regarding agreement was an interquartile range
      (IQR) >= 7; consensus regarding disagreement was an IQR <= 3. RESULTS: The expert
      panel addressed several topics including burden of disease, nail assessment,
      treatment goals and treatment options. The panel agreed that: it is extremely
      important to assess nail involvement in patients with psoriasis; nail assessments
      are rarely performed in routine clinical practice; full skin and nail clearance
      is an achievable goal with appropriate systemic therapy in patients with moderate
      to severe psoriasis with nail involvement. CONCLUSION: This article provides
      useful and practical considerations for the management and treatment of patients
      with moderate to severe skin and nail psoriasis.

PMID- 22151735
TI  - Experiences of treatment decision making for young people diagnosed with
      depressive disorders: a qualitative study in primary care and specialist mental
      health settings.
AB  - BACKGROUND: Clinical guidelines advocate for the inclusion of young people
      experiencing depression as well as their caregivers in making decisions about
      their treatment. Little is known, however, about the degree to which these groups
      are involved, and whether they want to be. This study sought to explore the
      experiences and desires of young people and their caregivers in relation to being
      involved in treatment decision making for depressive disorders. METHODS: Semi
      structured interviews were carried out with ten young people and five caregivers
      from one primary care and one specialist mental health service about their
      experiences and beliefs about treatment decision making. Interviews were audio
      taped, transcribed verbatim and analysed using thematic analysis. RESULTS:
      Experiences of involvement for clients varied and were influenced by clients
      themselves, clinicians and service settings. For caregivers, experiences of
      involvement were more homogenous. Desire for involvement varied across clients,
      and within clients over time; however, most clients wanted to be involved at
      least some of the time. Both clients and caregivers identified barriers to
      involvement. CONCLUSIONS: This study supports clinical guidelines that advocate
      for young people diagnosed with depressive disorders to be involved in treatment
      decision making. In order to maximise engagement, involvement in treatment
      decision making should be offered to all clients. Involvement should be
      negotiated explicitly and repeatedly, as desire for involvement may change over
      time. Caregiver involvement should be negotiated on an individual basis; however,
      all caregivers should be supported with information about mental disorders and
      treatment options.

PMID- 22151737
TI  - Reproducibility of retinal thickness measurements in eyes with uveitic macular
      oedema using Spectralis optical coherence tomography.

PMID- 22151736
TI  - Functional impairment of Tax-specific but not cytomegalovirus-specific CD8+ T
      lymphocytes in a minor population of asymptomatic human T-cell leukemia virus
      type 1-carriers.
AB  - BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell
      leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP) in a small percentage of infected individuals. ATL is often associated
      with general immune suppression and an impaired HTLV-1-specific T-cell response,
      an important host defense system. We previously found that a small fraction of
      asymptomatic HTLV-1-carriers (AC) already showed impaired T-cell responses
      against the major target antigen, Tax. However, it is unclear whether the
      impaired HTLV-1 Tax-specific T-cell response in these individuals is an HTLV-1
      specific phenomenon, or merely reflects general immune suppression. In this
      study, in order to characterize the impaired HTLV-1-specific T-cell response, we
      investigated the function of Tax-specific CD8+ T-cells in various clinical status
      of HTLV-1 infection. RESULTS: By using tetramers consisting of HLA-A*0201, 
      A*2402, or -A*1101, and corresponding Tax epitope peptides, we detected Tax
      specific CD8+ T-cells in the peripheral blood from 87.0% of ACs (n = 20/23) and
      100% of HAM/TSP patients (n = 18/18) tested. We also detected Tax-specific CD8+ T
      cells in 38.1% of chronic type ATL (cATL) patients (n = 8/21), although its
      frequencies in peripheral blood CD8+ T cells were significantly lower than those
      of ACs or HAM/TSP patients. Tax-specific CD8+ T-cells detected in HAM/TSP
      patients proliferated well in culture and produced IFN-gamma when stimulated with
      Tax peptides. However, such functions were severely impaired in the Tax-specific
      CD8+ T-cells detected in cATL patients. In ACs, the responses of Tax-specific
      CD8+ T-cells were retained in most cases. However, we found one AC sample whose
      Tax-specific CD8+ T-cells hardly produced IFN-gamma, and failed to proliferate
      and express activation (CD69) and degranulation (CD107a) markers in response to
      Tax peptide. Importantly, the same AC sample contained cytomegalovirus (CMV) pp65
      specific CD8+ T-cells that possessed functions upon CMV pp65 peptide stimulation.
      We further examined additional samples of two smoldering type ATL patients and
      found that they also showed dysfunctions of Tax-specific but not CMV-specific
      CD8+ T-cells. CONCLUSIONS: These findings indicated that Tax-specific CD8+ T
      cells were scarce and dysfunctional not only in ATL patients but also in a
      limited AC population, and that the dysfunction was selective for HTLV-1-specifc
      CD8+ T-cells in early stages.

PMID- 22151738
TI  - Studying relationships between environment and malaria incidence in Camopi
      (French Guiana) through the objective selection of buffer-based landscape
      characterisations.
AB  - BACKGROUND: Malaria remains a major health problem in French Guiana, with a mean
      of 3800 cases each year. A previous study in Camopi, an Amerindian village on the
      Oyapock River, highlighted the major contribution of environmental features to
      the incidence of malaria attacks. We propose a method for the objective selection
      of the best multivariate peridomestic landscape characterisation that maximises
      the chances of identifying relationships between environmental features and
      malaria incidence, statistically significant and meaningful from an
      epidemiological point of view. METHODS: A land-cover map, the hydrological
      network and the geolocalised inhabited houses were used to characterise the
      peridomestic landscape in eleven discoid buffers with radii of 50, 100, 200, 300,
      400, 500, 600, 700, 800, 900 and 1000 metres. Buffer-based landscape
      characterisations were first compared in terms of their capacity to discriminate
      between sites within the geographic space and of their effective
      multidimensionality in variable space. The Akaike information criterion (AIC) was
      then used to select the landscape model best explaining the incidences of P.
      vivax and P. falciparum malaria. Finally, we calculated Pearson correlation
      coefficients for the relationships between environmental variables and malaria
      incidence, by species, for the more relevant buffers. RESULTS: The optimal
      buffers for environmental characterisation had radii of 100 m around houses for
      P. vivax and 400 m around houses for P. falciparum. The incidence of P.
      falciparum malaria seemed to be more strongly linked to environmental features
      than that of P. vivax malaria, within these buffers. The incidence of P.
      falciparum malaria in children was strongly correlated with proportions of bare
      soil (r = -0.69), land under high vegetation (r = 0.68) and primary forest (r =
      0.54), landscape division (r = 0.48) and the number of inhabited houses (r = 
      0.60). The incidence of P. vivax malaria was associated only with landscape
      division (r = 0.49). CONCLUSIONS: The proposed methodology provides a simple and
      general framework for objective characterisation of the landscape to account for
      field observations. The use of this method enabled us to identify different
      optimal observation horizons around houses, depending on the Plasmodium species
      considered, and to demonstrate significant correlations between environmental
      features and the incidence of malaria.

PMID- 22151740
TI  - Fano-Rashba effect in thermoelectricity of a double quantum dot molecular
      junction.
AB  - We examine the relation between the phase-coherent processes and spin-dependent
      thermoelectric effects in an Aharonov-Bohm (AB) interferometer with a Rashba
      quantum dot (QD) in each of its arm by using the Green's function formalism and
      equation of motion (EOM) technique. Due to the interplay between quantum
      destructive interference and Rashba spin-orbit interaction (RSOI) in each QD, an
      asymmetrical transmission node splits into two spin-dependent asymmetrical
      transmission nodes in the transmission spectrum and, as a consequence, results in
      the enhancement of the spin-dependent thermoelectric effects near the spin
      dependent asymmetrical transmission nodes. We also examine the evolution of spin
      dependent thermoelectric effects from a symmetrical parallel geometry to a
      configuration in series. It is found that the spin-dependent thermoelectric
      effects can be enhanced by controlling the dot-electrode coupling strength. The
      simple analytical expressions are also derived to support our numerical
      results.PACS numbers: 73.63.Kv; 71.70.Ej; 72.20.Pa.

PMID- 22151739
TI  - Methylation of glycosylated sphingolipid modulates membrane lipid topography and
      pathogenicity of Cryptococcus neoformans.
AB  - In previous studies we showed that the replication of Cryptococcus neoformans in
      the lung environment is controlled by the glucosylceramide (GlcCer) synthase gene
      (GCS1), which synthesizes the membrane sphingolipid GlcCer from the C9-methyl
      ceramide. Here, we studied the effect of the mutation of the sphingolipid C9
      methyltransferase gene (SMT1), which adds a methyl group to position 9 of the
      sphingosine backbone of ceramide. The C. neoformans Deltasmt1 mutant does not
      make C9-methyl ceramide and, thus, any methylated GlcCer. However, it accumulates
      demethylated ceramide and demethylated GlcCer. The Deltasmt1 mutant loses more
      than 80% of its virulence compared with the wild type and the reconstituted
      strain. Interestingly, growth of C. neoformans Deltasmt1 in the lung was
      decreased and C. neoformans cells were contained in lung granulomas, which
      significantly reduced the rate of their dissemination to the brain reducing the
      onset of meningoencephalitis. Thus, using fluorescent spectroscopy and atomic
      force microscopy we compared the wild type and Deltasmt1 mutant and found that
      the altered membrane composition and GlcCer structure affects fungal membrane
      rigidity, suggesting that specific sphingolipid structures are required for
      proper fungal membrane organization and integrity. Therefore, we propose that the
      physical structure of the plasma membrane imparted by specific classes of
      sphingolipids represents a critical factor for the ability of the fungus to
      establish virulence.

PMID- 22151741
TI  - Rat tissue reaction to MTA FILLAPEX(r).
AB  - The aim of this study was to evaluate the rat subcutaneous tissue reaction to
      implanted polyethylene tubes filled with mineral trioxide aggregate (MTA)
      FILLAPEX(r) compared to the reaction to tubes filled with Sealapex(r) or Angelus
      MTA(r) . These materials were placed in polyethylene tubes and implanted into the
      dorsal connective tissue of Wistar rats for 7, 15, 30, 60, and 90 days. The
      specimens were stained with hematoxylin and eosin or Von Kossa or left unstained
      for examination under polarized light. Qualitative and quantitative evaluations
      of the reaction were performed. All materials caused moderate reactions after 7
      days, which decreased with time. The reactions were moderate and similar to that
      evoked by the control and Sealapex(r) on the 15th day. MTA FILLAPEX((r)) and
      Angelus MTA caused mild reactions beginning after 15 days. Mineralization and
      granulation birefringent to polarized light were observed with all materials. It
      was concluded that MTA FILLAPEX(r) was biocompatible and stimulated
      mineralization.

PMID- 22151742
TI  - Tumor necrosis factor-alpha (TNF-alpha) is a therapeutic target for impaired
      cutaneous wound healing.
AB  - Impaired wound healing states lead to substantial morbidity and cost with
      treatment resulting in an expenditure of billions of dollars per annum in the
      U.S. alone. Both chronic wounds and impaired acute wounds are characterized by
      excessive inflammation, enhanced proteolysis, and reduced matrix deposition.
      These confounding factors are exacerbated in the elderly, in part, as we report
      here, related to increased local and systemic tumor necrosis factor-alpha (TNF
      alpha) levels. Moreover, we have used a secretory leukocyte protease inhibitor
      (SLPI) null mouse model of severely impaired wound healing and excessive
      inflammation, comparable to age-related delayed human healing, to demonstrate
      that topical application of anti-TNF-alpha neutralizing antibodies blunts
      leukocyte recruitment and NFkappaB activation, alters the balance between M1 and
      M2 macrophages, and accelerates wound healing. Following antagonism of TNF-alpha,
      matrix synthesis is enhanced, associated with suppression of both inflammatory
      parameters and NFkappaB binding activity. Our data suggest that inhibiting TNF
      alpha is a critical event in reversing the severely impaired healing response
      associated with the absence of SLPI, and may be applicable to prophylaxis and/or
      treatment of impaired wound healing states in humans.

PMID- 22151743
TI  - Effects of endotoxin exposure on childhood asthma risk are modified by a genetic
      polymorphism in ACAA1.
AB  - BACKGROUND: Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been
      associated with asthma and atopy. We aimed to examine how genetic polymorphisms
      in innate immunity pathways interact with endotoxin to influence asthma risk in
      children. METHODS: In a previous analysis of 372 children from the Boston Home
      Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes
      (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways
      were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were
      associated with eczema. We tested these SNPs for interaction with early life
      endotoxin exposure (n = 291), in models for asthma and eczema by age 6. RESULTS:
      We found a significant interaction between endotoxin and a SNP (rs156265) in
      ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile)
      showed protective effects for asthma in individuals with at least one copy of the
      minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01).
      Endotoxin exposure did not reduce the risk of asthma in children homozygous for
      the major allele. CONCLUSION: Our findings suggest that protective effects of
      endotoxin exposure on asthma may vary depending upon the presence or absence of a
      polymorphism in ACAA1.

PMID- 22151744
TI  - Drinking behaviours and blood alcohol concentration in four European drinking
      environments: a cross-sectional study.
AB  - BACKGROUND: Reducing harm in drinking environments is a growing priority for
      European alcohol policy yet few studies have explored nightlife drinking
      behaviours. This study examines alcohol consumption and blood alcohol
      concentration (BAC) in drinking environments in four European cities. METHODS: A
      short questionnaire was implemented among 838 drinkers aged 16-35 in drinking
      environments in four European cities, in the Netherlands, Slovenia, Spain and the
      UK. Questions included self-reported alcohol use before interview and expected
      consumption over the remainder of the night. Breathalyser tests were used to
      measured breath alcohol concentration (converted to BAC) at interview. RESULTS:
      Most participants in the Dutch (56.2%), Spanish (59.6%) and British (61.4%)
      samples had preloaded (cf Slovenia 34.8%). In those drinking < 3 h at interview,
      there were no differences in BAC by gender or nationality. In UK participants,
      BAC increased significantly in those who had been drinking longer, reaching 0.13%
      (median) in females and 0.17% in males drinking > 5 h. In other nationalities,
      BAC increases were less pronounced or absent. High BAC (> 0.08%) was associated
      with being male, aged > 19, British and having consumed spirits. In all cities
      most participants intended to drink enough alcohol to constitute binge drinking.
      CONCLUSIONS: Different models of drinking behaviour are seen in different
      nightlife settings. Here, the UK sample was typified by continued increases in
      inebriation compared with steady, more moderate intoxication elsewhere. With the
      former being associated with higher health risks, European alcohol policy must
      work to deter this form of nightlife.

PMID- 22151745
TI  - Linking substance use with symptoms of subclinical psychosis in a community
      cohort over 30 years.
AB  - AIMS: The aim of the study was to examine the temporal associations between
      substance use and subclinical psychosis symptoms. DESIGN: Data from a prospective
      community study sampled within a single cohort over 30 years (1978-2008) were
      analysed with discrete-time hazard models. SETTING: General population-based
      sample. PARTICIPANTS: At initial sampling in 1978 males (n = 292) were 19 and
      females (n = 299) were 20 years old. MEASUREMENTS: Two psychosis syndromes
      representing 'schizotypal signs' and 'schizophrenia nuclear symptoms' and various
      substance use variables including cannabis, alcohol, tobacco and multiple-drug
      use (i.e. cannabis combined with other drugs). FINDINGS: In bivariate analyses,
      schizotypal signs were predominantly associated with regular cannabis use in
      adolescence (OR = 2.29, 95% CI 1.32-3.97). Schizophrenia nuclear symptoms were
      mainly related to alcohol (OR = 1.84, 95% CI 1.00-3.38) and multiple-drug use (OR
      = 2.35, 95% CI 1.38-4.02) during adolescence. Multivariate analyses showed that,
      in particular, regular cannabis use during adolescence was associated with the
      occurrence of subsequent schizotypal symptoms over a 30-year period (OR = 2.60,
      95% CI; 1.59-4.23), whereas multiple-drug use in adolescence was associated
      predominantly with schizophrenia nuclear symptoms (OR = 1.75, 95% CI 1.01-3.03).
      Alcohol misuse was only slightly associated with the onset of such symptoms.
      CONCLUSIONS: A significant portion of the occurrence of subclinical psychosis
      symptoms in adulthood can be attributed to excessive cannabis and multiple-drug
      use during adolescence. This is in line with the hypothesis that long-term
      sensitization of dopaminergic brain receptors plays a role in developing
      psychotic symptoms.

PMID- 22151746
TI  - Spatial and temporal variation in population genetic structure of wild Nile
      tilapia (Oreochromis niloticus) across Africa.
AB  - BACKGROUND: Reconstructing the evolutionary history of a species is challenging.
      It often depends not only on the past biogeographic and climatic events but also
      the contemporary and ecological factors, such as current connectivity and habitat
      heterogeneity. In fact, these factors might interact with each other and shape
      the current species distribution. However, to what extent the current population
      genetic structure reflects the past and the contemporary factors is largely
      unknown. Here we investigated spatio-temporal genetic structures of Nile tilapia
      (Oreochromis niloticus) populations, across their natural distribution in Africa.
      While its large biogeographic distribution can cause genetic differentiation at
      the paleo-biogeographic scales, its restricted dispersal capacity might induce a
      strong genetic structure at micro-geographic scales. RESULTS: Using nine
      microsatellite loci and 350 samples from ten natural populations, we found the
      highest genetic differentiation among the three ichthyofaunal provinces and
      regions (Ethiopian, Nilotic and Sudano-Sahelian) (R(ST) = 0.38 - 0.69). This
      result suggests the predominant effect of paleo-geographic events at macro
      geographic scale. In addition, intermediate divergences were found between rivers
      and lakes within the regions, presumably reflecting relatively recent
      interruptions of gene flow between hydrographic basins (R(ST) = 0.24 - 0.32). The
      lowest differentiations were observed among connected populations within a basin
      (R(ST) = 0.015 in the Volta basin). Comparison of temporal sample series revealed
      subtle changes in the gene pools in a few generations (F = 0 - 0.053). The
      estimated effective population sizes were 23 - 143 and the estimated migration
      rate was moderate (m ~ 0.094 - 0.097) in the Volta populations. CONCLUSIONS: This
      study revealed clear hierarchical patterns of the population genetic structuring
      of O. niloticus in Africa. The effects of paleo-geographic and climatic events
      were predominant at macro-geographic scale, and the significant effect of
      geographic connectivity was detected at micro-geographic scale. The estimated
      effective population size, the moderate level of dispersal and the rapid temporal
      change in genetic composition might reflect a potential effect of life history
      strategy on population dynamics. This hypothesis deserves further investigation.
      The dynamic pattern revealed at micro-geographic and temporal scales appears
      important from a genetic resource management as well as from a biodiversity
      conservation point of view.

PMID- 22151747
TI  - Akt1 deficiency modulates reward learning and reward prediction error in mice.
AB  - In contemporary reinforcement learning models, reward prediction error (RPE), the
      difference between the expected and actual reward, is thought to guide action
      value learning through the firing activity of dopaminergic neurons. Given the
      importance of dopamine in reward learning and the involvement of Akt1 in dopamine
      dependent behaviors, the aim of this study was to investigate whether Akt1
      deficiency modulates reward learning and the magnitude of RPE using Akt1 mutant
      mice as a model. In comparison to wild-type littermate controls, the expression
      of Akt1 proteins in mouse brains occurred in a gene-dosage-dependent manner and
      Akt1 heterozygous (HET) mice exhibited impaired striatal Akt1 activity under
      methamphetamine challenge. No genotypic difference was found in the basal levels
      of dopamine and its metabolites. In a series of reward-related learning tasks,
      HET mice displayed a relatively efficient method of updating reward information
      from the environment during the acquisition phase of the two natural reward tasks
      and in the reverse section of the dynamic foraging T-maze but not in
      methamphetamine-induced or aversive-related reward learning. The implementation
      of a standard reinforcement learning model and the Bayesian hierarchical
      parameter estimation show that HET mice have higher RPE magnitudes and that their
      action values are updated more rapidly among all three test sections in T-maze.
      These results indicate that Akt1 deficiency modulates natural reward learning and
      RPE. This study showed a promising avenue for investigating RPE in mutant mice
      and provided evidence for the potential link from genetic deficiency, to
      neurobiological abnormalities, to impairment in higher-order cognitive
      functioning.

PMID- 22151748
TI  - Predictive factors for cholangiocarcinoma associated with hepatolithiasis
      determined on the basis of Japanese Multicenter study.
AB  - AIM:   The aim of this study was to delineate predictive factors for
      cholangiocarcinoma in patients with hepatolithiasis, and to establish optimal
      management for hepatolithiasis from the viewpoint of carcinogenesis on the basis
      of a Japanese nationwide survey for hepatolithiasis. METHODS:   The
      Hepatolithiasis Research Group was organized in 2006 by the Ministry of Health,
      Labour and Welfare of Japan, and conducted a nationwide survey. The research
      group collected data on 336 cases of hepatolithiasis in 2006, in a cross
      sectional survey involving 2592 institutions in Japan. Predictive factors for
      cholangiocarcinoma associated with hepatolithiasis were analyzed by univariate
      and multivariate analyses of clinicopathological and therapeutic factors.
      RESULTS:   Twenty-three patients had cholangiocarcinoma. Histories of
      choledocoenterostomy and liver atrophy were found to be significantly predictive
      factors by multivariate analysis. In 87.5% of cases of cholangiocarcinoma with
      liver atrophy, cholangiocarcinoma was located in the atrophic lobes. The method
      of reconstruction did not affect the incidence of cholangiocarcinoma
      (choledochojejunostomy vs. choledochoduodenostomy; side-to-end vs. side-to-side
      anastomosis). CONCLUSIONS:   Choledocoenterostomy and liver atrophy may increase
      the risk of developing cholangiocarcinoma. Choledocoenterostomy is thus
      contraindicated in patients with hepatolithiasis. An aggressive resection
      strategy is recommended for an atrophic segment.

PMID- 22151749
TI  - Focal therapy for localised prostate cancer: are we asking the correct research
      questions?
AB  - The goals of focal therapy are laudable, namely reducing morbidity of treatment
      while ensuring at least equivalent oncological outcomes when compared with
      established interventions for localised prostate cancer, e.g. RP and external
      beam radiotherapy. While progress has been made towards better identifying the
      index lesion in these patients, there is much yet to be done to establish the
      validity of the index lesion theory as the metastatic focus and to establish that
      current targeting and ablative platforms are adequate to deliver the goals
      outlined above. The correct research questions have not yet been asked to
      establish either of these key principles underpinning focal therapy for localised
      prostate cancer.

PMID- 22151750
TI  - The Urology Foundation (TUF): where have we come from, where are we going?

PMID- 22151751
TI  - Two-stage urethroplasty with buccal mucosa.

PMID- 22151753
TI  - Infection after transrectal ultrasonography-guided prostate biopsy: increased
      relative risks after recent international travel or antibiotic use.

PMID- 22151756
TI  - Overexpression of Id3 induces apoptosis of A549 human lung adenocarcinoma cells.
AB  - OBJECTIVES: Inhibitor of differentiation 3 (Id3) protein has been implicated in
      the control of multiple cell death signalling pathways and in aetiology of
      numerous diseases. The aims of this study were to construct a recombinant
      eukaryotic expression vector (pEGFP/Id3), containing human Id3 (hId3) fused with
      enhanced green fluorescent protein (EGFP), and to determine effects of ectopic
      Id3 overexpression, on human lung adenocarcinoma cell (A549) proliferation.
      MATERIALS AND METHODS: Human Id3 cDNA was inserted into pEGFP-N1 vector to yield
      the recombinant eukaryotic expression vector pEGFP/Id3. Cells were transfected
      with pEGFP or pEGFP/Id3, and proliferation of EGFP-expressing cells was monitored
      by flow cytometry (FCM) and confocal fluorescence microscopy. RT-PCR,
      immunoblotting and immunocytochemistry were used to assess Id3 mRNA transcription
      and protein expression. Apoptosis was evaluated by Annexin V/7-AAD staining and
      FCM, while nuclear morphology of apoptotic cells was examined using Hoechst 33258
      staining. RESULTS: Over 4 days transfection with pEGFP, the proportion of EGFP
      positive A549 cells peaked at approximately 60% by 48 h and remained stable over
      the next 48 h. In contrast, the proportion of EGFP-positive cells in cultures
      transfected with pEGFP/Id3 decreased from a peak of 60% at 48 h to <5% at 96 h,
      suggesting that Id3 expression inhibited cell proliferation or survival. Annexin
      V/7-AAD and Hoechst 33258 staining revealed significantly higher rates of
      apoptosis in pEGFP/Id3-transfected cells. CONCLUSION: Overexpression of Id3
      triggered apoptosis in A549 human lung adenocarcinoma cells, implicating Id3 in
      negative control of tumour growth. These Id3-induced pro-apoptotic signalling
      pathways require further study, but this preliminary investigation suggests that
      Id3 regulation could be exploited in anti-tumour therapies.

PMID- 22151757
TI  - Online production tracking through author services.

PMID- 22151758
TI  - The clinical and research ethics of neuromodulation.

PMID- 22151759
TI  - Deep brain stimulation for dystonia: a meta-analysis.
AB  - Objective.  To use a meta-analysis on all reported cases of deep brain
      stimulation (DBS) for dystonia to determine which factors significantly influence
      outcome. The Burke-Fahn-Marsden (BFM) movement scale, the most reported measure,
      was chosen as the primary outcome measure for this analysis. Methods.  A MEDLINE
      search identified 137 patients who underwent DBS for dystonia in 24 studies that
      had individual BFM scores. Individual patient data, including age at onset of
      dystonia, age at surgery, gender, distribution of dystonia, etiology of dystonia,
      presence of associated features, abnormality of preoperative imaging, prior
      stereotactic surgeries, nucleus stimulated, type of anesthesia used, use of
      physiologic monitoring, type of imaging used for localization, stimulation
      parameters used, time of response to stimulation, and timing of outcome
      assessment were entered into an SPSS database for statistical analysis. Results. 
      The mean BFM percentage change (improvement in postoperative score from baseline)
      was 51.8% (range -34% to 100%). Significantly better outcomes were achieved with
      stimulation of the globus pallidus internus (GPi) than with stimulation of the
      posterior portion of the ventral lateral (VLp) nucleus of the thalamus (p =
      0.0001). The etiology of the dystonia also had a significant effect on outcomes.
      Statistically significant improvements in outcomes were seen for all etiologic
      categories, except encephalitis. Dystonia due to birth injury and encephalitis
      had significantly worse outcomes when compared to other etiologies. However,
      there were no significant differences in the outcomes of patients who were DYT1
      (DYT1 is the gene associated with the disorder Dystonia Musculorum Deformans)
      gene positive, DYT1 gene negative, or had pantothenate kinase-associated
      neurodegeneration (PKAN), tardive dyskinesia, and idiopathic and posttraumatic
      dystonias. Longer duration of dystonia symptoms correlated negatively with
      surgical outcome. A regression model using the three variables-stimulation site,
      etiology of dystonia, and duration of dystonia symptoms-explained 51% of the
      variance in outcomes. Conclusion.  Deep brain stimulation of the GPi provides
      significant improvement in BFM scores in a variety of dystonic conditions.

PMID- 22151760
TI  - Electromagnetic environmental influences on implanted deep brain stimulators.
AB  - Objective.  The objective of this study was to report our observations on the
      external electromagnetic field influences on deep brain stimulation (DBS) in our
      patient population and how these influences affected our patients' lives and
      other healthcare-related conditions. Materials and Methods.  We have
      retrospectively analyzed data concerning the effects of external electromagnetic
      fields on 172 of our patients implanted with DBS. Results.  Identifiable
      electromagnetic sources turned the implantable pulse generator (IPG) off in 20
      patients. In two patients, these episodes necessitated replacement of the Itrel
      II IPG (Medtronic Inc., Minneapolis, MN, USA) with the magnetically shielded
      Kinetra IPG (Medtronic Inc.). Six patients received cardiac pacemakers, leading,
      in two patients, to interference between the systems. Our experience concerning
      magnetic resonance imaging, electrocardiogram (ECG), heart defibrillation,
      electro-cautery, and other sources of electromagnetic interference also is
      described. Conclusions.  External electromagnetic interference may, in rare
      cases, constitute a severe threat to the well-being of the patient implanted with
      a DBS system. Also, malfunction of a DBS system may constitute a medical
      emergency. Nevertheless, in spite of these external electromagnetic influences,
      we consider DBS to be a safe method, provided safety protocols are followed, and
      provided that provider awareness about potential hazards is present.

PMID- 22151761
TI  - Multidimensional Outcomes Analysis of Intrathecal, Oral Opioid, and Behavioral
      Functional Restoration Therapy for Failed Back Surgery Syndrome: A Retrospective
      Study With 4 Years' Follow-up.
AB  - Study Design.  A retrospective design comparing three matched groups was used to
      evaluate the application of a multidimensional approach to outcomes analysis
      using a variety of disease-specific and generic outcome measures to assess three
      treatments for failed back surgery syndrome. Objective.  The objective of this
      study was to explore the use of a multidimensional analysis of outcomes to
      compare and contrast the effects of three different treatments: 1) intrathecal
      therapy using an implantable drug administration system (DAS), 2) standard
      medical therapy emphasizing the use of oral opioids (OO), and 3) residential pain
      and rehabilitation program (RPRP) for the treatment of chronic low back pain.
      Summary of Background Data.  The incidence of low back pain in patients with
      prior back surgery remains significant. Treatments for failed back surgery
      syndrome include interventional, pharmacologic, and functional restorative
      therapies. Outcome studies have rarely compared these three treatments over an
      extended follow-up period using both disease-specific and generic outcome
      measures. This study examined three groups of patients completing treatment in
      clinical setting with a 4-year follow-up. Methods.  Patients were selected from
      three different clinical treatment populations: DAS, OO, and RPRP. The three
      groups consisted of 40-50 patients each, matched on a number of demographic and
      pain variables. The average duration of follow-up for each group was about 4
      years. Data were collected on disease-specific outcome variables using Numerical
      Pain Ratings, the McGill Pain Questionnaire, the Beck Depression Inventory, the
      Oswestry Disability Scale, medication utilization, and other generic outcomes
      such as SF-36, Quality of Well-Being, Overall Improvement in Pain, and Patient
      Satisfaction. Information was obtained via chart review and telephone interviews
      with patients by a disinterested third party. Analysis of variance, chi-square
      test, and t-test were performed on the various dependent measures. Results.  The
      DAS group appeared to be superior to the OO and RPRP groups on 8 of 11 dependent
      measures, but only one dependent measure, the posttreatment numerical pain
      rating, was statistically significant. The RPRP group reported the highest
      Quality of Well-Being score, while the OO group had the highest level of patient
      satisfaction. Overall, each of the groups fell well below the "normal" range on
      generic measures, even when compared to other clinical populations. Measures of
      depression, subjective disability, and pain remained in the "moderate" range with
      little evidence of improved functioning or quality of life (QoL). Despite these
      findings, patients rated their overall improvement at 50-60% and reported high
      levels of satisfaction with their treatment. Conclusions.  The interpretation as
      to the most effective treatment depended on the particular outcome measure
      emphasized. There appeared to be a "disconnect" between ratings of pain,
      disability, mood, and QoL. The use of a multidimensional outcomes approach
      revealed a number of inconsistencies in the data, which could have been
      overlooked using only pain ratings and patient satisfaction data. No one
      treatment emerged as the most effective across all of the disease-specific and
      generic measures. However, patients in the DAS group tended to report greater
      improvement. Overall, although generally "satisfied" with treatment, they were
      generally "satisfied" with treatment despite continuing to report significant
      levels of pain, disability, and impaired QoL.

PMID- 22151762
TI  - The use of continuous intrathecal infusion of octreotide in patients with chronic
      pain of noncancer origin: an evaluation of efficacy in a prospective double-blind
      fashion.
AB  - Objective.  We evaluated the efficacy of octreotide when administered in a
      continuous fashion by intrathecal infusion. Materials and Methods.  We used a
      prospective, randomized, controlled, double-blinded method of analysis to
      evaluate the efficacy of intrathecal octreotide in a population of patients with
      noncancer pain diagnoses. The patients in this study had an unacceptable response
      to intrathecal opioids. In the analysis, the patients served as their own
      controls with a two-armed approach using a phase of treatment with preservative
      free saline and a phase of treatment with preservative-free octreotide to assess
      pain relief. Assessment tools used included visual analog scales and brief pain
      inventories. Results.  Of the 20 patients randomized in the study, 18 completed
      all data-collection points. One patient withdrew a week after the first refill
      because of uncontrollable pain, and the other patient withdrew early due to a
      lack of transportation. Statistical analysis showed no improvement in efficacy in
      the octreotide arm at the 6-week end-point when compared to saline. No
      significant differences were seen in any of the other end-points between the
      saline and intrathecal drug group. Conclusions.  Intrathecal octreotide did not
      show significant improvement in pain relief when compared to saline in chronic
      noncancer pain. It did show significant relief when compared to baseline,
      suggesting a positive effect of placebo in the control phase. While the overall
      data showed no clinical efficacy, a small group of patients did well and
      continued on the therapy in an open label fashion after the study concluded.
      These patients had pain consistent with a neuropathic pain diagnosis. The
      patients had noncancer pain, which was not responsive to intrathecal morphine.
      The lack of side-effects suggests that the dose selected for the study should be
      increased for future analysis of this agent, and patients with neuropathic pain
      should be more closely examined.

PMID- 22151763
TI  - Intraspinal therapy for the treatment of chronic pain: a review of the literature
      between 1990 and 2005 and suggested protocol for its rational and safe use.
AB  - The administration of intrathecal drugs has been shown to be efficacious in the
      treatment of both cancer pain and noncancer pain in patients who do not respond
      well to conventional treatment, in those who are unable to tolerate side-effects
      of opioids, and in those who constantly require significant increases in drug
      dosing. Although morphine represents the "drug of choice" for intrathecal
      administration, the use of alternative drugs (e.g., bupivacaine, clonidine, and
      hydromorphone) appears promising for intrathecal therapy of pain in patients who
      are unresponsive to morphine, those who cannot tolerate its side-effects, and
      those patients with neuropathic pain. This study analyzes results of studies
      published from 1990 to 2005 in order to evaluate the efficacy of intraspinal
      therapy.

PMID- 22151764
TI  - Lumbar spinal cord stimulation can improve muscle strength and gait independently
      of the analgesic effect: a case report.
AB  - Spinal cord stimulation (SCS) is widely used for pain relief in patients with
      failed back surgery syndrome (FBSS), and muscle weakness is a common finding in
      patients with chronic pain. We present here a single case report of a 47-year-old
      woman, who, after SCS for FBSS, had continuous improvement in lower leg muscle
      strength and gait, but only transient and minimal pain relief. To the authors'
      knowledge, this is only the second published case report of significant
      improvement in "motor" function, independent of the analgesic effect following
      SCS in FBSS. If SCS, in fact, does improve muscle strength, new strategies for
      the management of patients with chronic pain might be opened up. Further studies
      are needed to verify this hypothesis.

PMID- 22151765
TI  - Spinal cord stimulation has proven benefit on pain and quality of life in
      patients with angina pectoris when less invasive therapies have failed.
AB  - Background.  Since 1988, spinal cord stimulation (SCS) has been used at Odense
      University Hospital for patients with refractory angina pectoris. The aim of our
      prospective study was to evaluate the long-term effects of SCS on pain,
      activities of daily living (ADLs), quality of life (QOL), sleep hygiene, and
      physical functioning for patients with angina pectoris. Methods.  Before and
      after placement of SCS for patients with intractable angina pectoris, we
      performed structured telephone interviews questioning for pain relief, ADLs
      (Nottingham Health Profile), physical functioning (Seattle Angina Questionnaire)
      and sleep hygiene. Results.  Out of 150 patients with SCS over 15 years, 41
      patients had died, 46 patients had their devices explanted, and four patients did
      not participate or could not be reached. Three patients had less than 6 months of
      follow-up and were therefore not included in our analysis. The beneficial effects
      of SCS treatment for intractable angina pectoris were reduction in pain and
      improvement in QOL. Sleep pattern and physical functioning were not improved to
      the same extent as reduction in pain or improvement in QOL. Almost all of our SCS
      treated patients did recommend SCS for intractable angina pectoris. About 30% of
      patients discontinued treatment, the most common cause being electrode
      displacement and malfunction of the system. Other reasons for discontinued
      therapy were the evolvement of invasive treatment options such as coronary artery
      bypass graft and PTCA and use of such options in some patients during our
      prolonged observation period. Conclusion.  This survey shows that SCS leads to a
      70-80% improvement in pain, which, in turn, leads to improvement in QOL, whereas,
      physical condition and sleep pattern did not improve to the same extent.

PMID- 22151766
TI  - Clinical application of peroneal nerve stimulator system using percutaneous
      intramuscular electrodes for correction of foot drop in hemiplegic patients.
AB  - Objective.  To assess the orthotic effect of a functional electrical stimulation
      device (Akita Heel Sensor System; AHSS) in the treatment of hemiplegic gait with
      foot drop. Materials and Methods.  In the AHSS, a heel sensor is attached to a
      small plastic heel brace, and the peroneal nerve is stimulated via percutaneous
      intramuscular electrodes. During the swing phase of the hemiplegic gait, the
      common peroneal nerve is stimulated by the AHSS. Eight patients in chronic stages
      of hemiplegia participated in this study. Walking speeds and step cadences on a
      10-m course were compared between walking with stimulation and walking without
      stimulation. Results.  Mean walking speed (+/- SD) was 0.50 +/- 0.26 m/sec
      without stimulation and 0.64 +/- 0.31 m/sec with stimulation. The mean percentage
      increase in walking speed with stimulation was 30.1%. Mean step cadence was 31 +/
      7 steps/10 m without stimulation and 27 +/- 7 steps/10 m with stimulation. By
      correcting foot drop, the AHSS significantly increased walking speed and
      decreased cadence (p < 0.05). Conclusion.  The AHSS can significantly improve
      walking in hemiplegic patients with foot drop.

PMID- 22151767
TI  - Cheese wiring of an intrathecal catheter: an unusual cause of catheter leak.

PMID- 22151768
TI  - Does acute behavioral testing reflect successful ischemia in rats with transient
      middle cerebral artery occlusion?
AB  - BACKGROUND: Models of intraluminal middle cerebral artery occlusion present an
      intrinsic variability in infarct size. Behavioral evaluation is frequently
      performed during arterial occlusion to confirm success of surgery. AIMS AND/OR
      HYPOTHESIS: We compared the value of behavioral testing and multimodal magnetic
      resonance imaging performed during arterial occlusion for identifying
      successfully operated animals. METHODS: Rats were tested with behavioral
      assessment (using three scoring scales and the adhesive removal test) and
      multimodal magnetic resonance imaging (including magnetic resonance angiography,
      diffusion-weighted and perfusion-weighted imaging), both performed during the two
      hours of middle cerebral artery occlusion using the intraluminal suture model.
      Behavioral assessment was repeated 24 h after reperfusion, followed by sacrifice.
      RESULTS: Acute apparent diffusion coefficient lesion volume was correlated with
      both 2,3,5-triphenyl tetrazolium chloride infarct size (r = 0.75, P = 0.02) and
      behavioral status (r = 0.66, P = 0.05) on day one. Conversely, no correlation was
      found between acute behavioral examination and day one outcomes (2,3,5-triphenyl
      tetrazolium chloride infarct volume, r = 0.40, P = 0.28; behavioral examination,
      r = 0.39, P = 0.30). Day zero apparent diffusion coefficient volumes (P = 0.04),
      but not behavioral assessment (P = 0.60), discriminated animals with day one
      corticostriatal infarcts from these with subcortical infarcts. CONCLUSIONS: Acute
      behavioral testing performed during arterial occlusion fails to identify
      successfully operated animals. Acute diffusion magnetic resonance imaging may be
      more appropriate to assess and reduce infarct size variability in this model.

PMID- 22151769
TI  - Detecting experimental techniques and selecting relevant documents for protein
      protein interactions from biomedical literature.
AB  - BACKGROUND: The selection of relevant articles for curation, and linking those
      articles to experimental techniques confirming the findings became one of the
      primary subjects of the recent BioCreative III contest. The contest's Protein
      Protein Interaction (PPI) task consisted of two sub-tasks: Article Classification
      Task (ACT) and Interaction Method Task (IMT). ACT aimed to automatically select
      relevant documents for PPI curation, whereas the goal of IMT was to recognise the
      methods used in experiments for identifying the interactions in full-text
      articles. RESULTS: We proposed and compared several classification-based methods
      for both tasks, employing rich contextual features as well as features extracted
      from external knowledge sources. For IMT, a new method that classifies pair-wise
      relations between every text phrase and candidate interaction method obtained
      promising results with an F1 score of 64.49%, as tested on the task's development
      dataset. We also explored ways to combine this new approach and more
      conventional, multi-label document classification methods. For ACT, our
      classifiers exploited automatically detected named entities and other linguistic
      information. The evaluation results on the BioCreative III PPI test datasets
      showed that our systems were very competitive: one of our IMT methods yielded the
      best performance among all participants, as measured by F1 score, Matthew's
      Correlation Coefficient and AUC iP/R; whereas for ACT, our best classifier was
      ranked second as measured by AUC iP/R, and also competitive according to other
      metrics. CONCLUSIONS: Our novel approach that converts the multi-class, multi
      label classification problem to a binary classification problem showed much
      promise in IMT. Nevertheless, on the test dataset the best performance was
      achieved by taking the union of the output of this method and that of a multi
      class, multi-label document classifier, which indicates that the two types of
      systems complement each other in terms of recall. For ACT, our system exploited a
      rich set of features and also obtained encouraging results. We examined the
      features with respect to their contributions to the classification results, and
      concluded that contextual words surrounding named entities, as well as the MeSH
      headings associated with the documents were among the main contributors to the
      performance.

PMID- 22151771
TI  - Monitoring endangered freshwater biodiversity using environmental DNA.
AB  - Freshwater ecosystems are among the most endangered habitats on Earth, with
      thousands of animal species known to be threatened or already extinct. Reliable
      monitoring of threatened organisms is crucial for data-driven conservation
      actions but remains a challenge owing to nonstandardized methods that depend on
      practical and taxonomic expertise, which is rapidly declining. Here, we show that
      a diversity of rare and threatened freshwater animals--representing amphibians,
      fish, mammals, insects and crustaceans--can be detected and quantified based on
      DNA obtained directly from small water samples of lakes, ponds and streams. We
      successfully validate our findings in a controlled mesocosm experiment and show
      that DNA becomes undetectable within 2 weeks after removal of animals, indicating
      that DNA traces are near contemporary with presence of the species. We further
      demonstrate that entire faunas of amphibians and fish can be detected by high
      throughput sequencing of DNA extracted from pond water. Our findings underpin the
      ubiquitous nature of DNA traces in the environment and establish environmental
      DNA as a tool for monitoring rare and threatened species across a wide range of
      taxonomic groups.

PMID- 22151770
TI  - Gene CNVs and protein levels of complement C4A and C4B as novel biomarkers for
      partial disease remissions in new-onset type 1 diabetes patients.
AB  - OBJECTIVE: To determine the roles of complement C4A and C4B gene copy-number
      variations and their plasma protein concentrations in residual insulin secretion
      and loss of pancreatic beta-cell function in new-onset type 1 diabetes (T1D)
      patients. METHODS: We studied 34 patients of European ancestry with new-onset
      T1D, aged between 3 and 17 yr (10.7 +/- 3.45), at Nationwide Children's Hospital
      in Columbus, Ohio. Gene copy-number and size variations of complement C4A and C4B
      were determined by genomic Southern blot analyses. C4A and C4B protein phenotypes
      were elucidated by immunofixation and radial immunodiffusion. Two-digit human
      leukocyte antigen (HLA)-DRB1 genotypes were determined by sequence-specific
      polymerase chain reaction. At 1- and 9-month post diagnosis, stimulated C-peptide
      levels were measured after a standardized mixed-meal tolerance test. RESULTS: The
      diploid gene copy-numbers of C4A varied from 0 to 4, and those of C4B from 0 to
      3. Patients with higher copy-number of C4A or higher C4A plasma protein
      concentrations at diagnosis had higher C-peptide levels at 1-month post diagnosis
      (p = 0.008; p = 0.008). When controlled by the Z-score of body mass index, C4A
      copy-numbers, C4A protein concentrations, the age of disease onset, and the
      number of HLA-DR3 but not DR4 alleles were significant parameters in determining
      C-peptide levels. At 9-month post diagnosis, 42.3% of patients remained in
      partial remission, and these patients were characterized by lower total C4B copy
      numbers or lower C4B protein concentrations (p = 0.02; p = 0.0004). CONCLUSIONS:
      C4A appears to associate with the protection of residual beta-cell function in
      new-onset T1D; C4B is correlated with the end of disease remission at 9-month
      post diagnosis.

PMID- 22151772
TI  - Gait improvement in patients with cerebral palsy by visual and auditory feedback.
AB  - OBJECTIVES:   To study the effects of gait training with visual and auditory
      feedback cues on the walking abilities of patients with gait disorders due to
      cerebral palsy. MATERIALS AND METHODS:   Visual and auditory feedback cues were
      generated by a wearable device, driven by inertial sensors. Ten randomly selected
      patients with gait disorders due to cerebral palsy and seven age-matched healthy
      individuals trained with visual feedback cues, while ten patients and eight age
      matched healthy individuals trained with auditory feedback cues. Baseline
      performance (walking speed and stride length along a 10-m straight track) was
      measured before device use. Following 20-min training with the device and a 20
      min break, performance without the device was measured again and compared with
      the baseline performance. RESULTS:   For the patients who trained with visual
      feedback, the average improvement was 21.70% +/- 36.06% in the walking speed and
      8.72% +/- 9.47% in the stride length. For the patients who trained with auditory
      feedback, the average improvement was 25.43% +/- 28.65% in the walking speed and
      13.58% +/- 13.10% in the stride length. For the healthy individuals who trained
      with visual feedback, the average improvement was -2.41% +/- 9.54% in the walking
      speed and -2.84% +/- 10.11% in the stride length. For the healthy individuals who
      trained with auditory feedback, the average improvement was 0.01% +/- 7.73% in
      the walking speed and -2.03% +/- 6.15% in the stride length. CONCLUSIONS:  
      Training with visual and auditory feedback cues can improve gait parameters in
      patients with gait disorders due to cerebral palsy. This was contrasted by no
      improvement in age-matched healthy individuals.

PMID- 22151773
TI  - Effects on incident reporting after educating residents in patient safety: a
      controlled study.
AB  - BACKGROUND: Medical residents are key figures in delivering health care and an
      important target group for patient safety education. Reporting incidents is an
      important patient safety domain, as awareness of vulnerabilities could be a
      starting point for improvements. This study examined effects of patient safety
      education for residents on knowledge, skills, attitudes, intentions and behavior
      concerning incident reporting. METHODS: A controlled study with follow-up
      measurements was conducted. In 2007 and 2008 two patient safety courses for
      residents were organized. Residents from a comparable hospital acted as external
      controls. Data were collected in three ways: 1] questionnaires distributed
      before, immediately after and three months after the course, 2] incident
      reporting cards filled out by course participants during the course, and 3]
      residents' reporting data gathered from hospital incident reporting systems.
      RESULTS: Forty-four residents attended the course and 32 were external controls.
      Positive changes in knowledge, skills and attitudes were found after the course.
      Residents' intentions to report incidents were positive at all measurements.
      Participants filled out 165 incident reporting cards, demonstrating the skills to
      notice incidents. Residents who had reported incidents before, reported more
      incidents after the course. However, the number of residents reporting incidents
      did not increase. An increase in reported incidents was registered by the
      reporting system of the intervention hospital. CONCLUSIONS: Patient safety
      education can have immediate and long-term positive effects on knowledge, skills
      and attitudes, and modestly influence the reporting behavior of residents.

PMID- 22151774
TI  - Editorial.

PMID- 22151775
TI  - A new device for securing intrathecal and epidural catheters.

PMID- 22151776
TI  - National Italian Register of Implantable Systems for Spinal Cord Stimulation
      (SCS): Analysis of Preliminary Data.
AB  - The aim of this work is to assess quality of treatment and to monitor drawbacks
      of SCS implantation systems through a National Observational Center. Data were
      obtained through a questionnaire sent by post or via telephone to each patient.
      All patients were affected by chronic-'vascular' and "neuropathic" pain.
      Questionnaires were handed out to 463 patients. So far the returned
      questionnaires have accounted for 72% (with men accounting for 58% and women for
      42%). The data obtained concern the decade between 1988 and 1999. Eighty-one
      percent of patients reported a positive assessment for pain control with
      neurostimulation; there was a lowering of drug needs in 71% of patients after
      implantation; 10% of patients reported problems with the use of their stimulator;
      an improvement in quality of life was reported by 63% of patients; 94% of
      patients enrolled in the registry expressed a positive judgement on their pain
      therapy center; and 87% of patients would make the same choice again, considering
      SCS to be a valid treatment for their condition. We conclude that the methodology
      used is consistent with that of previous studies on nonmalignant chronic pain.
      The data obtained also reveal implantation hardware reliability, regardless of
      clinical outcome. A low percentage of complications and a high degree of patient
      satisfaction are also to be stressed.

PMID- 22151777
TI  - Continuous intrathecal baclofen infusion by a programmable pump in 131
      consecutive patients with severe spasticity of spinal origin.
AB  - We began this study to determine the efficacy and safety of intrathecal baclofen
      (ITB) delivered by a programmable pump for the treatment of severe spasticity of
      spinal cord origin. One hundred fifty two patients with severe spasticity of
      spinal origin, refractory to oral baclofen, or who experienced intolerable side
      effects were given a test dose of ITB. Only those who had a satisfactory response
      were considered to be appropriate for pump implantation. All but one of the 152
      patients had a satisfactory response, and the pump was implanted in 131 patients.
      Pre- and postoperative spasticity scores were compared and analyzed. The mean
      Ashworth score for rigidity decreased from 4.2 preoperatively to 1.3 (p < 0.0005)
      on ITB. The spasm score decreased from a mean of 3.4 to 0.6 (p < 0.0005).
      Reduction of spasticity resulted in improved levels of physical activity,
      decreased pain, and augmentation of sleep. Drug-related complications included
      constipation, muscular hypotonia, urinary retention, erectile dysfunction,
      nausea, dizziness, drowsiness, hypotension and bradycardia as well as tolerance
      to baclofen. Some patients experienced post-spinal puncture headaches. Catheter
      related problems included occlusions, breaks, punctures, and dislodgments.
      Superficial pump pocket infection, pocket erosion, cerebrospinal fluid (CSF)
      leak, post-spinal puncture headache, and meningitis were some of the procedure
      related complications. Two pumps flipped and another pump valve was stuck. We
      conclude that long-term intrathecal baclofen by an implanted programmable pump is
      a safe and effective method of treating severe intractable spinal spasticity.

PMID- 22151778
TI  - Which Neuronal Elements are Activated Directly by Spinal Cord Stimulation.
AB  - The purpose of this paper is to discuss which nerve fibers in the various
      quadrants of the spinal cord are immediately activated under normal conditions of
      spinal cord stimulation, ie, at voltages within the therapeutic range. The
      conclusions are based on both empirical and computer modeling data. The
      recruitment of dorsal column (DC) fibers is most likely restricted to Abeta
      fibers with a diameter >= 10.7 MUm in a 0.20-0.25 mm layer under the pia mater
      and fibers of 9.4-10.7 MUm in an even smaller outer layer when a conventional SCS
      lead is used. In a 0.25-mm outer layer of the T11 segment the number of Abeta
      fibers >= 10.7 MUm, as estimated in a recent morphometric study, is about 56 in
      each DC. Because a DC at T11 innervates 12 dermatomes, a maximum of 4-5 fibers
      (>= 10.7 MUm) may be recruited in each dermatome near the discomfort threshold.
      The dermatome activated just below the discomfort threshold is likely to be
      stimulated by just a single fiber, suggesting that paresthesia and pain relief
      may be effected in a dermatome by the stimulation of a single large Abeta fiber.
      The depth of stimulation in the DCs, and thereby the number of recruited Abeta
      fibers, may be increased 2-3 fold when stimulation is applied by an optimized
      electrode configuration (a narrow bi/tripole or a transverse tripole). Assuming
      that the largest Abeta fibers in a dorsal root have a diameter of 15 MUm, the
      smallest ones recruited at discomfort threshold would be 12 MUm. The latter are
      presumably of proprioceptive origin and responsible for segmental reflexes and
      uncomfortable sensations. Furthermore, it is shown to be unlikely that, apart
      from dorsal roots and a thin outer layer of the DCs, any other spinal structures
      are recruited when stimulation is applied in the dorsal epidural space. Finally,
      anodal excitation and anodal propagation block are unlikely to occur with SCS.

PMID- 22151779
TI  - Peripheral nerve stimulation for unremitting ophthalmic postherpetic neuralgia.
AB  - Postherpetic neuralgia (PHN) is a common cause of chronic pain in the elderly.
      Opioids and adjunctive analgesics such as antidepressants and anticonvulsants
      effectively reduce discomfort in many patients, while others have pain that
      remains resistant to all forms of therapy. Spinal cord stimulation has shown
      promise for severe truncal and extremity PHN, but has no impact on neuralgias of
      cranial nerve origin. Peripheral nerve stimulation has been described for such
      problems as chronic regional pain syndrome, but to date has not been reported for
      cranial nerve syndromes. This article describes the cases in which an 86-year-old
      man and a 76-year-old woman with intractable PHN of greater than 6 and 4 years,
      respectively, were effectively treated with peripheral nerve stimulation of the
      ophthalmic division of the trigeminal nerve.

PMID- 22151780
TI  - Spina bifida occulta as a relative contraindication for percutaneous retrograde
      lead insertion for sacral nerve root stimulation.
AB  - Percutaneous retrograde lead insertion for sacral nerve root stimulation is a
      newly described technique being applied to a variety of pain disorders. The
      success of the procedure rests in a defined epidural space such that there is
      unimpeded progression of the lead into the desired location. It is hypothesized
      that any condition that results in anatomic compromise of the epidural space
      would prevent the success of the procedure. Two patients with biopsy-proven
      interstitial cystitis and intractable pain were referred to the senior author for
      evaluation. Percutaneous retrograde lead insertion for sacral nerve root
      stimulation was performed on these patients in a standard fashion (1,2).
      Intraoperative fluoroscopy verified the diagnosis of spina bifida occulta. In one
      patient, implantation was completed percutaneously, but later two of the leads
      were found to have been placed intradurally. In another patient, repeated
      attempts at passing the epidural lead distal to the congenital defect were
      unsuccessful, and the percutaneous procedure was aborted. In conclusion, we have
      found that the diagnosis of spina bifida occulta, or any other condition in which
      the epidural space is anatomically disrupted, is a relative contraindication for
      this procedure. Preoperative roentograms of the lumbar spine may be helpful in
      avoiding technical difficulties due to this diagnosis.

PMID- 22151781
TI  - Real Time Foot Drop Correction using Machine Learning and Natural Sensors.
AB  - The objective of this study was to investigate and test a real time system
      implemented for Functional Electrical Stimulation (FES) assisted foot drop
      correction, deriving control timing from signals recorded from a peripheral
      sensory nerve. A hemiplegic participant was attached with a cuff electrode on the
      sural nerve connected to a telemetry controlled implanted neural amplifier, and a
      stimulation cuff electrode on the peroneal nerve connected to an implanted
      stimulator. An input domain was derived from the recorded electroneurogram (ENG)
      and fed to a detection algorithm based on an Adaptive Logic Network (ALN) for
      controlling the timing of the peroneal stimulation. The detection system was
      tested in real time over a period of 392 days, covering a variety of walking
      tasks. The detection system's ability to detect heel strike and foot lift without
      errors and to detect the difference between walking and standing proved to be
      stable for the duration of the study. We conclude that using ALNs and natural
      sensors provide a stable and accurate control signal for FES foot drop
      correction.

PMID- 22151782
TI  - Neurorehabilitation of upper extremities in humans with sensory-motor impairment.
AB  - Today most clinical investigators agree that the common denominator for
      successful therapy in subjects after central nervous system (CNS) lesions is to
      induce concentrated, repetitive practice of the more affected limb as soon as
      possible after the onset of impairment. This paper reviews representative methods
      of neurorehabilitation such as constraining the less affected arm and using a
      robot to facilitate movement of the affected arm, and focuses on functional
      electrotherapy promoting the movement recovery. The functional electrical therapy
      (FET) encompasses three elements: 1) control of movements that are compromised
      because of the impairment, 2) enhanced exercise of paralyzed extremities, and 3)
      augmented activity of afferent neural pathway. Liberson et al. (1) first reported
      an important result of the FET; they applied a peroneal stimulator to enhance
      functionally essential ankle dorsiflexion during the swing phase of walking.
      Merletti et al. (2) described a similar electrotherapeutic effect for upper
      extremities; they applied a two-channel electronic stimulator and surface
      electrodes to augment elbow extension and finger extension during different reach
      and grasp activities. Both electrotherapies resulted in immediate and carry-over
      effects caused by systematic application of FET. In studies with subjects after a
      spinal cord lesion at the cervical level (chronic tetraplegia) (3-5) or stroke
      (6), it was shown that FET improves grasping and reaching by using the following
      outcome measures: the Upper Extremity Function Test (UEFT), coordination between
      elbow and shoulder movement, and the Functional Independence Measure (FIM).
      Externally applied electrical stimuli provided a strong central sensory input
      which could be responsible for the changes in the organization of impaired
      sensory-motor mechanisms. FET resulted in stronger muscles that were stimulated
      directly, as well as exercising other muscles. The ability to move paralyzed
      extremities also provided awareness (proprioception and visual feedback) of
      enhanced functional ability as being very beneficial for the recovery. FET
      contributed to the increased range of movement in the affected joints, increased
      speed of joint rotations, reduced spasticity, and improved functioning measured
      by the UEFT, the FIM and the Quadriplegia Index of Function (QIF).

PMID- 22151783
TI  - Professor Patrick D Wall FRS.

PMID- 22151784
TI  - On the weight of indels in genomic distances.
AB  - BACKGROUND: Classical approaches to compute the genomic distance are usually
      limited to genomes with the same content, without duplicated markers. However,
      differences in the gene content are frequently observed and can reflect important
      evolutionary aspects. A few polynomial time algorithms that include genome
      rearrangements, insertions and deletions (or substitutions) were already
      proposed. These methods often allow a block of contiguous markers to be inserted,
      deleted or substituted at once but result in distance functions that do not
      respect the triangular inequality and hence do not constitute metrics. RESULTS:
      In the present study we discuss the disruption of the triangular inequality in
      some of the available methods and give a framework to establish an efficient
      correction for two models recently proposed, one that includes insertions,
      deletions and double cut and join (DCJ) operations, and one that includes
      substitutions and DCJ operations. CONCLUSIONS: We show that the proposed
      framework establishes the triangular inequality in both distances, by summing a
      surcharge on indel operations and on substitutions that depends only on the
      number of markers affected by these operations. This correction can be applied a
      posteriori, without interfering with the already available formulas to compute
      these distances. We claim that this correction leads to distances that are
      biologically more plausible.

PMID- 22151785
TI  - Comparison of therapeutic effects of garlic and d-Penicillamine in patients with
      chronic occupational lead poisoning.
AB  - Previous studies on animals have revealed that garlic (Allium sativum) is
      effective in reducing blood and tissue lead concentrations. The aim of this study
      was to investigate therapeutic effects of garlic and compare it with d
      penicillamine in patients with chronic lead poisoning. After coordination and
      obtaining informed consent, clinical examinations and blood lead concentration
      (BLC) of 117 workers at a car battery industry were investigated. BLC was
      determined by heated graphite atomization technique of an atomic absorption
      spectrometer. The workers were randomly assigned into two groups of garlic (1200
      MUg allicin, three times daily) and d-penicillamine (250 mg, three times daily)
      and treated for 4 weeks. BLC was determined again 10days post-treatment. Clinical
      signs and symptoms of lead poisoning were also investigated and compared with the
      initial findings. Clinical improvement was significant in a number of clinical
      manifestations including irritability (p = 0.031), headache (p = 0.028),
      decreased deep tendon reflex (p=0.019) and mean systolic blood pressure (0.021)
      after treatment with garlic, but not d-penicillamine. BLCs were reduced
      significantly (p=0.002 and p=0.025) from 426.32+/-185.128 to 347.34+/-121.056
      MUg/L and from 417.47+/-192.54 to 315.76+/-140.00MUg/L in the garlic and d
      penicillamine groups, respectively, with no significant difference (p=0.892)
      between the two groups. The frequency of side effects was significantly (p=0.023)
      higher in d-penicillamine than in the garlic group. Thus, garlic seems safer
      clinically and as effective as d-penicillamine. Therefore, garlic can be
      recommended for the treatment of mild-to-moderate lead poisoning.

PMID- 22151786
TI  - Reprogramming of gastrointestinal cancer cells.
AB  - Cell reprogramming reverts cells to multipotent, preprogrammed states by re
      establishing epigenetic markers. It can also induce considerable malignant
      phenotype modification. Because key events in cancer relapse and metastasis,
      including epithelial-mesenchymal transition phenotypes, are regulated primarily
      by reversible and transient epigenetic modifications rather than the accumulation
      of irreversible and stable genetic abnormalities, studying dynamic mechanisms
      regulating these biological processes is important. Transcription factors for
      induced pluripotent stem cells and non-coding microRNAs allow pluripotent
      phenotype induction. We present the current knowledge of the possible
      applications of cell reprogramming in reducing aggressive phenotype expression,
      which can induce tumor cell hibernation and maintain appropriate phenotypes,
      thereby minimizing relapse and metastasis after surgical resection of
      gastrointestinal cancer.

PMID- 22151787
TI  - Endophthalmitis following cataract surgery: the role of prophylactic
      postoperative chloramphenicol eye drops.
AB  - PURPOSE: The main aim of the study was to assess whether omitting prophylactic
      postoperative topical antibiotics (chloramphenicol) influenced the risk of
      developing endophthalmitis after cataract surgery. METHODS: We conducted a
      retrospective study including all patients who had cataract surgery at our
      outpatient cataract unit between 2004 and 2011. Postoperative topical antibiotics
      (chloramphenicol) were omitted from 2007 onwards, as was the first postoperative
      day review. Patients with a diagnosis of endophthalmitis after cataract surgery
      were extracted, and the rate of postoperative endophthalmitis (PE) before and
      after changing these routines was compared. The diagnosis of PE was defined as
      severe intraocular inflammation requiring prompt vitreous sampling for culture.
      RESULTS: Seven thousand one hundred and twenty-three and 8131 cataract surgeries
      were performed in the following periods: January 2004 through December 2006
      (period 1) and January 2007 through December 2010 (period 2), respectively. Five
      cases of PE were identified in period 1 (0.070%) and four patients in period 2
      (0.049%). The median time between cataract surgery and onset of symptoms was 6
      days in period 1 and 4.5 days in period 2. Median time for intervention was 7 and
      5 days postsurgery, respectively. CONCLUSION: We found no difference in the
      frequency of PE following cataract surgery when changing the postoperative
      topical medication from a mixture of corticosteroids and antibiotics to only
      corticosteroids.

PMID- 22151788
TI  - Barriers and enablers to implementation of a New Zealand-wide guideline for
      assessment and management of cardiovascular risk in primary health care: a
      template analysis.
AB  - AIM: The aim of this study was to identify the enablers and barriers to guideline
      implementation in a primary healthcare setting by employing the Promoting Action
      on Research Implementation in Health Services (PARIHS) framework as a template
      for data analysis and interpretation. BACKGROUND: The use of clinical practice
      guidelines is pivotal to improving health outcomes. However, the implementation
      of guidelines into practice is complex, unpredictable, and, in spite of much
      investigation, remains resistant to explanation of what works and why. Optimising
      the enablers and minimising the barriers to implementation of a guideline for
      reducing cardiovascular disease risk has the potential to significantly reduce
      the burden of disease. The PARIHS framework has been successfully applied in a
      number of clinical contexts and has been found useful in illuminating the
      barriers and enablers to evidence implementation. APPROACH: This qualitative
      study involved focus groups with 20 primary healthcare nurses, 4 general
      practitioners, 5 managers, and individual interviews with 3 funder/planners who
      discussed their contribution to the use of a guideline for the assessment and
      management of cardiovascular risk. Template analysis based on the PARIHS
      framework was applied to semi-structured narrative data to provide an in-depth
      analysis of the barriers and enablers to implementation of the guideline.
      CONCLUSIONS: The lack of facilitation of the guideline into practice was a major
      barrier to implementation. Implementation plans that address the concerns and
      complexities of everyday practice are an essential aspect of guideline
      development. The PARIHS framework was found to be comprehensive and accommodating
      of the complexity of everyday practice associated with guideline implementation
      in primary health care. The pertinence of the framework confirms its usefulness
      as a tool to guide implementation.

PMID- 22151789
TI  - Very high vitamin D supplementation rates among infants aged 2 months in
      Vancouver and Richmond, British Columbia, Canada.
AB  - BACKGROUND: Vitamin D deficiency during infancy may lead to rickets and possibly
      other poor health outcomes. The World Health Organization recommends exclusive
      breastfeeding for the first 6 months. Breast milk is the best food for infants
      but does not contain adequate vitamin D. Health Canada recommends all breastfed
      infants receive a daily vitamin D supplement of 400 IU; however, there appears to
      be limited current Canadian data as to whether parents or caregivers are
      following this advice. The aim of this study was to determine the rates of
      vitamin D supplementation among 2-month old infants in Vancouver and Richmond,
      British Columbia, Canada. METHODS: Mothers of all healthy infants born between
      April and May 2010 were approached to participate. Telephone surveys were
      conducted with 577 mothers (response rate 56%) when their infants turned 2
      months. RESULTS: Over half of the infants received only breast milk in the week
      prior to the survey. One third received a mixture of breast milk and infant
      formula and 10% received only formula. About 80% of the infants were supplemented
      with vitamin D at 2 months. Infants who received only breast milk were most
      likely to be supplemented with vitamin D (91%). Over 60% of the infants had a
      total vitamin D intake of 300- < 500 IU/d from supplements and formula and only
      5% did not receive any vitamin D. Most parents were advised to give vitamin D
      supplement by health professionals, such as public health nurses, midwives, and
      doctors. CONCLUSIONS: About 90% of the infants received breast milk at 2 months
      of age. The vitamin D supplementation rate was 80%. Future studies are needed to
      monitor breastfeeding duration and vitamin D supplementation rates as infants get
      older.

PMID- 22151790
TI  - Vitamin A metabolism is changed in donors after living-kidney transplantation: an
      observational study.
AB  - BACKGROUND: The kidneys are essential for the metabolism of vitamin A (retinol)
      and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin.
      Little is known about changes in serum concentration after living donor kidney
      transplantation (LDKT) as a consequence of unilateral nephrectomy; although an
      association of these parameters with the risk of cardiovascular diseases and
      insulin resistance has been suggested. Therefore we analyzed the concentration of
      retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and
      respective recipients at baseline as well as 6 weeks and 6 months after LDKT.
      RESULTS: As a consequence of LDKT, the kidney function of recipients was improved
      while the kidney function of donors was moderately reduced within 6 weeks after
      LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels
      of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors.
      After LDKT, the levels of all four parameters decreased in serum of the
      recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors
      increased and remained increased during the follow-up period of 6 months.
      CONCLUSION: LDKT is generally regarded as beneficial for allograft recipients and
      not particularly detrimental for the donors. However, it could be demonstrated in
      this study that a moderate reduction of kidney function by unilateral
      nephrectomy, resulted in an imbalance of components of vitamin A metabolism with
      a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of
      donors.

PMID- 22151791
TI  - Risk factors of gallbladder cancer in Karachi-a case-control study.
AB  - BACKGROUND: Gallbladder carcinoma (GC) is a relatively rare malignancy worldwide
      but is the second commonest gastrointestinal cancer in Pakistani women.
      Gallstones have a positive association with GC but other factors also influence
      in causation. METHODS: This is a retrospective case control study over a period
      of 19 years. The cases (Group A) were patients with histopathological proven
      carcinoma gallbladder (N = 60) and controls were patients with cholelithiasis but
      no carcinoma gallbladder on histopathology (N = 120). Multivariate regression
      analysis was done to calculate the odds ratio, 95% confidence interval and P
      Value. A positive relationship was found between size of stone > 1 cm, solitary
      stone, age > 55 years and multi-parity in women. RESULTS: There were 60 patients
      in Group A and 120 patients in Group B. mean age of diagnosis in Group A patients
      was 57 +/- 2.4 years while mean age of diagnosis in Group B patients was 48 +/-
      1.35 years. Sixty seven percent of cancer group patients were female as compared
      to 78% females in non-cancer group. In Group A, 69% of female patients were
      multiparous (parity of more than 5) while 43% of group B patients were
      multiparous. For body mass index (BMI), both groups were not very different in
      our study population i.e. around 78% patients in each group has BMI of more than
      23 Kg/m2. In Group A, 37% (n = 22) have solitary stones as compared to 15% (n =
      18) in group B. similarly Group A patients has larger stone size as compared to
      Group B i.e.59% (n = 36) patients in Group A have stones of more than 1 cm when
      compared to 35% (n = 41) patients in Group B. After using multivariate regression
      analysis, age more than 55 years (OR - 7.27, p value- < 0.001), solitary stone
      (OR - 3.33, p value - 0.002) and stone of more than 1 cm (OR - 2.73, p value -
      0.004) were found to be independent risk factors for development of gallbladder
      cancer. CONCLUSION: Most of the patients (78%) with GC were female, and the
      statistically significant risk factors were older age, solitary stones and stones
      size more than one centimeter. A case can be made for prophylactic
      cholecystectomy in such a high risk group. However a population based study is
      required to calculate the true incidence of GC in Karachi and a prospective multi
      center study is needed to produce strong evidence for screening and prophylactic
      cholecystectomy. TRIAL REGISTRATION: As this was a retrospective review of
      medical records, as per institution policy, its gives waiver from any
      registration (ethical/trial).

PMID- 22151793
TI  - Photodynamic therapy for actinic keratosis in organ transplant patients.
AB  - BACKGROUND: The incidence of actinic keratoses (AK) and non-melanoma skin cancer
      (NMSC) in organ transplant recipients (OTRs) is significantly higher than in
      immunocompetent patients. Rates of progression and recurrence following treatment
      are higher too, in part due to the effects of the immunosuppressant drugs.
      Conventional therapies for AK, using curettage, cryotherapy, surgical excision,
      topical therapies and photodynamic therapy (PDT), are often less effective, and
      may be inappropriate, for treating the greater numbers and extent of lesions in
      OTRs. Moreover, there are no specific protocols for treating this patient
      population that take into account the need for more frequent treatment and the
      increased pain associated with treating larger areas. OBJECTIVES: Recently, a pan
      European group of dermatologists with expertise in this area met to share current
      best practice in PDT for the treatment of AK in OTRs. METHODS: The group
      identified areas where PDT currently is not meeting the needs of these patients
      and discussed how these gaps might be addressed. RESULTS/CONCLUSIONS: This
      position article summarizes those discussions and makes recommendations
      concerning a standardized protocol for treating OTRs, for a large randomized
      controlled trial to provide robust data on safety, efficacy and optimal pain
      control, and to provide pharmaco-economics data that can be used to support
      extended reimbursement in this patient group. The authors also recommend a second
      clinical trial to further investigate induced immunosuppression with PDT in
      healthy volunteers.

PMID- 22151794
TI  - Possible widespread presence of hepatitis A virus subgenotype IIIA in Japan:
      Recent trend of hepatitis A causing acute liver failure.
AB  - AIM:   Recently, the number of acute hepatitis A cases has decreased in Japan.
      However, six patients with acute liver failure caused by hepatitis A virus (HAV)
      have been admitted to Chiba University Hospital, Japan, in the last 18 months,
      between 2010 and June 2011. The aim of this study is to characterize the recent
      HAV genotypes from an urban hospital in Japan and to compare the clinical
      differences. METHODS:   Hepatitis A virus RNA was detected by strand-specific
      reverse transcription. Then, HAV VP1/2A regions were amplified by nested
      polymerase chain reaction (PCR). Sequences were directly determined and
      phylogenetic trees were constructed for determining HAV subgenotypes. RESULTS:  
      Analysis of these HAV genomes revealed that 4 and 2 belonged to subgenotypes IA
      and IIIA, respectively. CONCLUSIONS:   Fujiwara et al. reported a frequency of
      HAV subgenotype IIIA of only 2.1% in Japan. We conclude that HAV subgenotype IIIA
      might be widespread in our country.

PMID- 22151792
TI  - The prototype HIV-1 maturation inhibitor, bevirimat, binds to the CA-SP1 cleavage
      site in immature Gag particles.
AB  - BACKGROUND: Bevirimat, the prototype Human Immunodeficiency Virus type 1 (HIV-1)
      maturation inhibitor, is highly potent in cell culture and efficacious in HIV-1
      infected patients. In contrast to inhibitors that target the active site of the
      viral protease, bevirimat specifically inhibits a single cleavage event, the
      final processing step for the Gag precursor where p25 (CA-SP1) is cleaved to p24
      (CA) and SP1. RESULTS: In this study, photoaffinity analogs of bevirimat and mass
      spectrometry were employed to map the binding site of bevirimat to Gag within
      immature virus-like particles. Bevirimat analogs were found to crosslink to
      sequences overlapping, or proximal to, the CA-SP1 cleavage site, consistent with
      previous biochemical data on the effect of bevirimat on Gag processing and with
      genetic data from resistance mutations, in a region predicted by NMR and
      mutational studies to have alpha-helical character. Unexpectedly, a second region
      of interaction was found within the Major Homology Region (MHR). Extensive prior
      genetic evidence suggests that the MHR is critical for virus assembly.
      CONCLUSIONS: This is the first demonstration of a direct interaction between the
      maturation inhibitor, bevirimat, and its target, Gag. Information gained from
      this study sheds light on the mechanisms by which the virus develops resistance
      to this class of drug and may aid in the design of next-generation maturation
      inhibitors.

PMID- 22151795
TI  - Preparation, characterization and in vivo evaluation of pH-sensitive oral insulin
      loaded poly(lactic-co-glycolicacid) nanoparticles.
AB  - AIM: Oral administration of insulin is a promising drug delivery system for
      diabetic patients as it is convenient and reduces pain, two of the major
      contributors to non-compliance. METHODS: In this study, insulin was encapsulated
      in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) by using double
      emulsion/solvent evaporation technique and analyses on its release kinetics were
      carried out using both in vitro and in vivo methods. RESULTS: First, only by this
      simple methods, release speed of insulin from NPs can be controlled in different
      pH solution. The rate of release of insulin was found to be slower in acidic pH;
      about 90% of insulin was released in 11 days at pH 1.0. In alkaline conditions,
      the release was faster; about 90% release was observed to occur within 3 days at
      pH 7.8. The insulin-loaded poly (lactic-co-glycolic acid) nanoparticles (PINPs)
      were administered orally to diabetes mellitus-induced rats and the response of
      blood glucose and insulin levels was estimated. Blood glucose decreased and the
      concentration of insulin in animal blood increased. In diabetic animals which
      were administered intermittent insulin, every 8 h, blood glucose levels were
      maintained equivalently with those of healthy rats. CONCLUSION: These
      experimental results indicated that oral PINPs are able to deliver insulin
      effectively and decrease animal blood sugar; in conclusion, this may be a
      promising delivery system for the treatment of diabetes.

PMID- 22151796
TI  - Early and late calcium waves during wound healing in corneal endothelial cells.
AB  - Immediately after wounding, bovine corneal endothelial cells develop a fast
      calcium wave that propagates from the wound border to the rest of the monolayer
      and extinguishes in approximately 5 minutes. One hour after wounding, a late,
      slow calcium wave (SCW) develops concomitantly to the depolarization of the
      plasma membrane potential of the border cells. The incorporation of inhibitors of
      the epithelial sodium channel and of the sodium-calcium exchanger produces
      inhibition of the membrane depolarization and the SCW, and diminishes the rate of
      wound healing. The L-type calcium channel blocker nimodipine does not have any
      effect on the SCW. The reversible inhibition of the fast calcium wave does not
      affect the SCW and only slightly decreases the velocity of healing. Our results
      suggest that the SCW is at least partially produced by the coupling of the
      epithelial sodium channel and the sodium-calcium exchanger functioning in reverse
      mode. They also suggest that the SCW may play a role in the overall healing
      process.

PMID- 22151797
TI  - Comparison of the fracture resistance of simulated immature permanent teeth using
      various canal filling materials and fiber posts.
AB  - BACKGROUND:   The purpose of this study was to compare the fracture resistances
      of immature teeth treated with MTA along with root canal obturation methods using
      AH Plus, MetaSEAL, MTA Fillapex sealers + lateral compaction technique, and
      Unicore quartz fiber posts. MATERIALS AND METHODS:   Fifty single-rooted
      maxillary anterior teeth were divided into five groups. The crowns were dissected
      and root canals were enlarged. #6 Peeso reamers were allowed to protrude 1 mm.
      beyond the apex to simulate immature teeth. The apical 4-5 mm of each tooth was
      filled using Angelus white MTA. The remaining portions of canals were obturated
      as follows: Group 1: No backfilling (control), Group 2: AH Plus + gutta-percha,
      lateral compaction, Group 3: MetaSEAL + gutta-percha, lateral compaction, Group
      4: MTA Fillapex + gutta-percha, lateral compaction, Group 5: UniCore Fiber posts
      luted using PermaFlo DC. The specimens were embedded into self-curing acrylic
      poured into identical cylinders which were mounted on a jig providing a 45
      degrees  angle. A compressive load increasing at 1 mm min(-1) was applied and the
      maximum load at which fracture occurred was recorded. Statistical analysis was
      performed using Kruskal-Wallis and Dunn's multiple tests. RESULTS:   The highest
      fracture resistance was obtained with Group 5 (Fiber posts) whereas Group 4 (MTA
      Fillapex) yielded the lowest values. The mean fracture resistance value of Group
      2 (AH Plus) was significantly higher than Group 4 (MTA Fillapex) (P = 0.001). The
      mean fracture value of Group 5 (Fiber posts) was significantly higher than Group
      2 (AH Plus), Group 3 (MetaSEAL), and Group 4 (MTA Fillapex) (P = 0.02, 0.004, and
      0.0001, respectively). CONCLUSION:   Within the limitations of this study,
      UniCore quartz fiber posts provided the highest resistance. This methodology may
      specifically be advantageous for teeth with arrest of development at early
      stages, as these teeth are more susceptible to fracture owing to their
      excessively weak dentinal walls.

PMID- 22151798
TI  - Involvement of transcription factor p53 and leptin in control of porcine ovarian
      granulosa cell functions.
AB  - The aim of our in vitro experiments was to examine the role of transcription
      factor p53 and the metabolic hormone leptin, in controlling basic functions
      (proliferation, apoptosis and secretory activity) of ovarian cells, as well as
      involvement of p53 in mediating or modulating actions of leptin, on ovarian
      cells. Porcine ovarian granulosa cells, transfected and non-transfected with a
      gene construct encoding p53, were cultured with leptin (at concentrations of 0,
      1, 10 or 100 ng/ml). Accumulation of p53 and of apoptosis-related (bax) and
      proliferation-related (PCNA, cyclin B1) substances was evaluated by SDS-PAGE
      western blotting. Secretion of progesterone (P4) was measured by RIA.
      Transfection with the p53 gene construct promoted accumulation of this
      transcription factor within cells. It also stimulated expression of bax (which
      can be thought of as a marker of apoptosis), and reduced accumulation of
      proliferation-related substances PCNA and cyclin B1. Overexpression of p53
      resulted in reduced P4 secretion. Leptin, when added alone, increased
      accumulation of p53, bax and PCNA, decreased accumulation of cyclin B1 and had no
      effect on P4 secretion. Transfection of cells with p53 gene construct reversed
      effects of leptin on cyclin B1 and induced stimulatory effects of leptin on P4
      release, but did not modify leptin action on p53, bax and PCNA. These multiple
      effects of the p53 gene construct on granulosa cells, cultured with and without
      leptin, (i) demonstrate that leptin can be involved in control of porcine ovarian
      cell proliferation, apoptosis and expression of p53, but not on P4 release; and
      (ii) confirm involvement of p53 in promoting apoptosis and suppression of
      proliferation and P4 secretion in these cells. (iii) The similarity of p53 and
      leptin's actions on bax and cyclin B1, and inability of p53 to further promote
      leptin action on this parameter suggest that p53 can be a mediator of leptin's
      action on ovarian cell apoptosis. (iv) On the other hand, p53 can modulate, but
      probably not mediate the effects of leptin on ovarian cell proliferation and P4
      release.

PMID- 22151799
TI  - Plasma vitamin C assay in women of reproductive age in Kampala, Uganda, using a
      colorimetric method.
AB  - OBJECTIVE: Vitamin C alone or in combination with vitamin E has been proposed to
      prevent pre-eclampsia. In this study, we assayed the plasma vitamin C in women of
      reproductive age in Kampala and assessed its association with pre-eclampsia.
      METHODS: Participants in this study were 215 women with pre-eclampsia, 400 women
      with normal pregnancy attending antenatal clinic and 200 non-pregnant women
      attending family planning clinic at Mulago Hospital's Department of Obstetrics
      and Gynaecology from 1st May 2008 to 1st May 2009. Plasma vitamin C was assayed
      using the acid phosphotungstate method; differences in the means of plasma
      vitamin C were determined by ANOVA. RESULTS: Mean plasma vitamin C levels were
      1.72 (SD 0.68)*10(3)MUg/l in women with pre-eclampsia, 1.89 (SD 0.73)*10(3)MUg/l
      in women with normal pregnancy and 2.64 (SD 0.97)*10(3)MUg/l in non-pregnant
      women. Plasma vitamin C was lower in women with pre-eclampsia than in women with
      normal pregnancy (P=0.005) and non-pregnant women (P<0.001). CONCLUSION: Health
      workers need to advise women of reproductive age on foods that are rich in
      vitamin C, as this may improve the vitamin status and possibly reduce the
      occurrence of pre-eclampsia.

PMID- 22151800
TI  - Digitate hyperkeratosis.

PMID- 22151801
TI  - High resolution profiling of human exon methylation by liquid hybridization
      capture-based bisulfite sequencing.
AB  - BACKGROUND: DNA methylation plays important roles in gene regulation during both
      normal developmental and disease states. In the past decade, a number of methods
      have been developed and applied to characterize the genome-wide distribution of
      DNA methylation. Most of these methods endeavored to screen whole genome and
      turned to be enormously costly and time consuming for studies of the complex
      mammalian genome. Thus, they are not practical for researchers to study multiple
      clinical samples in biomarker research. RESULTS: Here, we display a novel
      strategy that relies on the selective capture of target regions by liquid
      hybridization followed by bisulfite conversion and deep sequencing, which is
      referred to as liquid hybridization capture-based bisulfite sequencing (LHC-BS).
      To estimate this method, we utilized about 2 MUg of native genomic DNA from
      YanHuang (YH) whole blood samples and a mature dendritic cell (mDC) line,
      respectively, to evaluate their methylation statuses of target regions of exome.
      The results indicated that the LHC-BS system was able to cover more than 97% of
      the exome regions and detect their methylation statuses with acceptable allele
      dropouts. Most of the regions that couldn't provide accurate methylation
      information were distributed in chromosomes 6 and Y because of multiple mapping
      to those regions. The accuracy of this strategy was evaluated by pair-wise
      comparisons using the results from whole genome bisulfite sequencing and
      validated by bisulfite specific PCR sequencing. CONCLUSIONS: In the present
      study, we employed a liquid hybridisation capture system to enrich for exon
      regions and then combined with bisulfite sequencing to examine the methylation
      statuses for the first time. This technique is highly sensitive and flexible and
      can be applied to identify differentially methylated regions (DMRs) at specific
      genomic locations of interest, such as regulatory elements or promoters.

PMID- 22151802
TI  - Observational study on efficacy of negative expiratory pressure test proposed as
      screening for obstructive sleep apnea syndrome among commercial interstate bus
      drivers--protocol study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a respiratory disease characterized
      by the collapse of the extrathoracic airway and has important social implications
      related to accidents and cardiovascular risk. The main objective of the present
      study was to investigate whether the drop in expiratory flow and the volume
      expired in 0.2 s during the application of negative expiratory pressure (NEP) are
      associated with the presence and severity of OSA in a population of professional
      interstate bus drivers who travel medium and long distances. METHODS/DESIGN: An
      observational, analytic study will be carried out involving adult male subjects
      of an interstate bus company. Those who agree to participate will undergo a
      detailed patient history, physical examination involving determination of blood
      pressure, anthropometric data, circumference measurements (hips, waist and neck),
      tonsils and Mallampati index. Moreover, specific questionnaires addressing sleep
      apnea and excessive daytime sleepiness will be administered. Data acquisition
      will be completely anonymous. Following the medical examination, the participants
      will perform a spirometry, NEP test and standard overnight polysomnography. The
      NEP test is performed through the administration of negative pressure at the
      mouth during expiration. This is a practical test performed while awake and
      requires little cooperation from the subject. In the absence of expiratory flow
      limitation, the increase in the pressure gradient between the alveoli and open
      upper airway caused by NEP results in an increase in expiratory flow. DISCUSSION:
      Despite the abundance of scientific evidence, OSA is still underdiagnosed in the
      general population. In addition, diagnostic procedures are expensive, and
      predictive criteria are still unsatisfactory. Because increased upper airway
      collapsibility is one of the main determinants of OSA, the response to the
      application of NEP could be a predictor of this disorder. With the enrollment of
      this study protocol, the expectation is to encounter predictive NEP values for
      different degrees of OSA in order to contribute toward an early diagnosis of this
      condition and reduce its impact and complications among commercial interstate bus
      drivers. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clinicos (local
      acronym RBEC) [Internet]: Rio de Janeiro (RJ): Instituto de Informacao Cientifica
      e Tecnologica em Saude (Brazil); 2010 - Identifier RBR-7dq5xx. Cross-sectional
      study on efficacy of negative expiratory pressure test proposed as screening for
      obstructive sleep apnea syndrome among commercial interstate bus drivers; 2011
      May 31 [7 pages]. Available from http://www.ensaiosclinicos.gov.br/rg/RBR
      7dq5xx/.

PMID- 22151804
TI  - The "new look and feel" of neuromodulation.

PMID- 22151805
TI  - A comment on vadera et Al. "Intrathecal granuloma and intramedullary abscess
      associated with an intrathecal morphine pump".

PMID- 22151806
TI  - Intrathecal granuloma and intramedullary abscess associated with an intrathecal
      morphine pump.
AB  - Objective and Importance.  Several previous reports have documented cord
      compression resulting from the formation of an intrathecal inflammatory mass in
      patients using intrathecal drug delivery systems. We present the first reported
      case of an intramedullary abscess and intrathecal inflammatory mass associated
      with an intrathecal drug delivery system. Clinical Presentation.  A 47-year-old
      man was transferred to our institution from an outside hospital with a 3-week
      history of the inability to ambulate or move his legs. His medical history
      included multiple failed back surgeries for back pain that had been effectively
      managed after the implantation of an intrathecal drug delivery system eight years
      prior. Upon presentation to us, his examination showed no movement in his lower
      extremities with pinprick-preserved sensation in his toes. Imaging showed an
      intrathecal mass at the catheter tip, at spinal level T10 and T11. Contrast
      enhanced imaging indicated an intramedullary abscess at T11 and T12 level.
      Intervention.  The patient underwent T10-L1 laminectomies with complete resection
      of the inflammatory mass, catheter tip, and explantation of the intrathecal drug
      delivery pump. A midline myelotomy also was performed to aspirate the abscess and
      the cavity was profusely irrigated. Pathology studies demonstrated that the
      inflammatory mass contained chronic inflammatory markers and necrotic tissue. The
      abscess was linked to infection with Streptococcus anginosus. Conclusion. 
      Generally, inflammatory masses forming along the catheter tip are not associated
      with infections. We report the first case of an intramedullary abscess associated
      with an intrathecal drug delivery pump.

PMID- 22151803
TI  - The insertion/deletion (I/D) polymorphism in the Angiotensin-converting enzyme
      gene and cancer risk: a meta-analysis.
AB  - BACKGROUND: The insertion/deletion (I/D) polymorphism in the Angiotensin
      converting enzyme (ACE) gene has been implicated in susceptibility to cancer, but
      a large number of studies have reported inconclusive results. The aim of this
      study is to assess the association between the I/D polymorphism in the ACE gene
      and cancer risk by meta-analysis. METHODS: A search was performed in Pubmed
      database, Embase database, Chinese Biomedical (CBM) database, China National
      Knowledge Infrastructure (CNKI) database and Weipu database, covering all studies
      until August 31, 2010. Statistical analysis was performed by using Revman4.2 and
      STATA 10.0. RESULTS: A total of 25 case-control studies comprising 3914 cancer
      patients and 11391 controls were identified. No significant association was found
      between the I/D polymorphism and over all cancer risks (OR = 0.88, 95%CI = 0.73
      1.06, P = 0.17 for DD+DI vs. II). In the subgroup analysis by ethnicity, no
      significant association was found among Asians and Europeans for the comparison
      of DD+DI vs. II. In the subgroup analysis by cancer types, no significant
      associations were found among lung cancer, breast cancer, prostate cancer,
      colorectal cancer, gastric cancer for the comparison of DD+DI vs. II. Results
      from other comparative genetic models also indicated the lack of associations
      between this polymorphism and cancer risks. CONCLUSIONS: This meta-analysis
      suggested that the ACE D/I polymorphism might not contribute to the risk of
      cancer.

PMID- 22151807
TI  - A new and alternative leads positioning for complex regional pain syndrome
      treatment: paraforaminal stimulation.
AB  - We present a case of a female patient suffering from type I complex regional pain
      syndrome (CRPS) who developed "mirror imaging" of her CRPS and was successfully
      treated with dual spinal cord stimulation (SCS) in the paraforaminal epidural
      space. This patient initially had unilateral pain that was unsuccessfully treated
      with midline SCS and single-lead lateral epidural lead placement
      "paraforaminally." One year later, because we believed that paraforaminal
      stimulation would preferentially stimulate primary sensitized afferents
      innervating the painful area, we reperformed SCS with two leads positioned
      laterally and paraforaminally close to the roots within the epidural space. After
      repositioning and after 1 year of paraforaminal stimulation, there was
      significant improvement in the patient's symptoms, resolving all unilateral and
      "mirrored" symptoms. We conclude that paraforaminal stimulation may be a valid
      therapeutic option for the treatment of CRPS.

PMID- 22151808
TI  - The Laparoscopic Implantation of Neuroprothesis (LION) Procedure to Control
      Intractable Abdomino-Pelvic Neuralgia.
AB  - Objective.  To present different aspects and advantages of the laparoscopic
      implantation of a peripheral nerve stimulator adjacent to the pelvic nerves,
      aimed at treating intractable pelvic neuralgia by means of neuromodulation-the
      laparoscopic implantation of neuroprothesis (LION) procedure. Materials and
      Methods.  We report here a series of three patients with different types and
      etiologies of chronic pelvic neuralgia who underwent laparoscopy for implantation
      of a peripheral nerve stimulator for neuromodulation, the first for
      neuromodulation of the ilioinguinal and pudendal nerves, the second for
      neuromodulation of the sciatic nerve, and the third for neuromodulation of the
      sacral nerve roots. In all three patients, the neuralgia was refractory to
      medical management and had profound socioeconomic consequences for the patients.
      Results.  Laparoscopic implantation of neuroelectrodes was successfully performed
      in all three patients and resulted significant diminution of pain without need
      for further medical treatment. Conclusions.  Laparoscopy allows optimal
      implantation of electrodes on all pelvic nerves through a minimally invasive
      approach. In addition, it permits new applications of neuromodulation for pelvic
      polyneuropathies or mononeuropathy, not covered by classical spinal cord or
      transcutaneous techniques.

PMID- 22151809
TI  - Avoiding complications from spinal cord stimulation: practical recommendations
      from an international panel of experts.
AB  - Spinal cord stimulation (SCS) is an effective technique for the relief of
      neuropathic pain. Biologic complications are more prevalent within the first 3
      months after implantation, are generally minor and reversible, and do not affect
      patients' acceptance of the treatment. Technically, hardware-related
      complications are uncommon and occur more frequently in the first 2 years
      following implantation of the device than after. Nevertheless, the incidence of
      technological complications can be relatively high if the technique is not
      performed correctly. Based on a review of the literature and on the experience
      and consensus of an expert panel, this manuscript attempts to provide practical
      guidelines, which may help implanters avoid some of the technological
      complications of SCS implantation. Areas covered by this article include patient
      positioning, the appropriate use of imaging, insertion of percutaneous and
      surgical leads, intraoperative stimulation, lead choice and suturing,
      considerations pre- and postimplantation, stimulation settings and regimens,
      implantable pulse generator positioning, and control of infections. It is hoped
      that these guidelines may help physicians to improve their SCS implantation
      technique and thereby improve the outcomes of the therapy. These guidelines
      should be of special value for newer centers starting SCS therapy for their
      patients.

PMID- 22151810
TI  - Effects of electrode positioning on perception threshold and paresthesia coverage
      in spinal cord stimulation.
AB  - Objectives.  This pilot study aims to validate the hypothesis that a smaller
      distance between spinal cord stimulation (SCS) lead and spinal cord results in
      more extensive paresthesia and less energy consumption. Materials and Methods. 
      After insertion of a percutaneous SCS lead in patients with chronic pain
      (condition A), a first catheter was temporarily placed alongside the lead
      (condition B), and a second catheter was placed on the other side of the lead
      (condition C). In all three conditions paresthesia coverage, perception threshold
      (PT) of paresthesia, and maximum comfortable (MC) stimulus amplitude were
      determined and the catheters were subsequently removed. Results.  Paresthesia
      coverage in all six patients was increased markedly in condition C when compared
      to condition A, whereas the mean values of PT, MC, and therapeutic range (MC/PT)
      dropped by 22%, 14%, and 13%, respectively. Conclusions.  The results suggest
      that paresthesia coverage is increased when the space between the SCS lead and
      spinal cord gets smaller, whereas PT and energy consumption are reduced.

PMID- 22151811
TI  - Pain relief by transcutaneous electric nerve stimulation with bidirectional
      modulated sine waves in patients with chronic back pain: a randomized, double
      blind, sham-controlled study.
AB  - Objectives.  Newly developed bidirectional modulated sine waves (BMW) might
      provide some derived benefit to patients with low back pain. Pain relief by
      transcutaneous electric nerve stimulation (TENS) with BMWs was tested. Materials
      and Methods.  Analgesic effects of BMWs and conventional bidirectional pulsed
      waves on chronic back pain in 28 patients were compared, and effects of repeated
      TENS using BMWs on chronic back pain were investigated in 21 patients by means of
      a randomized double-blind, sham-controlled, parallel-group method. Pain intensity
      was assessed using numerical rating scale (NRS). Results.  There was significant
      immediate reduction in NRS in patients receiving BMWs, and 60 min after treatment
      compared to sham TENS. Weekly repeated treatments using massage and TENS with
      BMWs for 5 weeks resulted in a decrease of NRS, but there were no significant
      differences between the TENS plus massage and sham TENS plus massage groups.
      Conclusions.  This study shows that TENS with BMWs significantly inhibits chronic
      back pain, and treatment effects are attained within a day. The results also
      suggest that there were no statistically significant long-term effects of TENS
      with BMW in the repeated treatment.

PMID- 22151812
TI  - Continuous vagus nerve stimulation effects on the gut-brain axis in Swine.
AB  - Objectives.  This study was designed to assess vagus nerve stimulation effects on
      the food intake pattern in swine and determine the electrical stimulus direction.
      Material and Methods.  Fifteen Large White pigs were randomly divided into three
      groups, groups A-C. All animals underwent implantation of a vagus nerve
      stimulator at the gastro-esophogeal junction. In group A, the stimulation was
      switched off, whereas stimulation was switched on in groups B and C. Food intake
      and body weight were registered in groups A and B, but not in group C, which was
      used to measure direction of stimulation in the vagus and effect on heart rate
      and blood pressure. Variables measured in group C included the bispectral index,
      blood pressure, and heart rate. A Student's t-test and one-way analysis of
      variance were used to detect differences between groups. All animals were
      sacrificed to identify effects of implantation and stimulation on the vagus
      nerve. Results.  With respect to food intake, there was no difference between
      groups A and B; however, body weight did register a continuous increase. During
      stimulation, in group C arterial pressures decreased significantly, whereas the
      heart rate and bispectral index increased. Conclusion.  The stimulation protocol
      applied in this study was insufficient to cause changes in the feeding behavior
      of swine; however, it did increase central nervous system activity.

PMID- 22151813
TI  - Walking on an uneven surface: the effect of common peroneal stimulation on gait
      parameters and relationship between perceived and measured benefits in a sample
      of participants with a drop-foot.
AB  - Objectives.  To examine the effect of using a common peroneal stimulator on an
      even and an uneven surface, and to compare measures with perceived response to
      stimulation. Method.  Participants had a drop-foot caused by a stroke (N = 13) or
      multiple sclerosis (N = 7) and had used a common peroneal stimulator for > 3
      months prior to the study. Walking speed and physiological cost index (PCI) were
      recorded under four conditions: with and without stimulation over an even and an
      uneven surface. Participants also completed a questionnaire. Results.  A
      statistically significant increase in walking speed and decrease in PCI was
      identified when the stimulator was used. There was a trend to greater improvement
      on the uneven compared to the even surface. A correlation between perceived
      benefit of stimulation and a measured decrease in PCI was detected. Conclusion. 
      Stimulation may be particularly beneficial for the more difficult task of walking
      on an uneven surface. Perceived benefit was related to a reduction in effort of
      walking, not in increased speed.

PMID- 22151814
TI  - The force-velocity relationship of paralyzed quadriceps muscles during functional
      electrical stimulation cycling.
AB  - Objectives.  To investigate the nature of the force-velocity relationship on
      muscle forces and power outputs during functional electrical stimulation (FES)
      evoked cycling at different pedaling cadences. Materials and Methods.  Ten
      patients with T4-T9 spinal cord injuries (ASIA A) performed FES-evoked cycling at
      50 rev/min using a motorized isokinetic ergometer for 20 min, after which
      quadriceps crank torque and power were measured at 10, 30, and 50 rev/min.
      Results.  Pedal cadence affected both the shape and the magnitudes of the
      quadriceps torque and power curves. Significantly greater average torque (T) and
      peak crank torques (PTi) were elicited at lower pedal cadences (T(10)  > T(50) ,
      p < 0.001; PTi(10)  > PTi(50) , p = 0.007). Instantaneous peak power (PPi) and
      average power output (PO) increased significantly with pedal cadence, such that
      PPi(50)  and PPi(30)  > PPi(10)  (p < 0.001) and PO(50)  or PO(30)  > PO(10)  (p
      < 0.001). At the higher cadences, peak torque and peak power were developed at
      significantly later angles (p < 0.001). Conclusions.  The force-velocity
      relationship of muscle has a significant effect upon the muscle forces produced
      during FES-evoked cycling. However, muscle force rise times and fatigue within
      FES-evoked contractions, especially at a low cadence, should be considered when
      making comparisons between different FES-cycling cadences.

PMID- 22151815
TI  - Response to shellock et Al. "Vagus nerve stimulation therapy system: in vitro
      evaluation of magnetic resonance imaging-related heating and function at 1.5 and
      3 tesla".

PMID- 22151816
TI  - Response to kainz.

PMID- 22151817
TI  - Response to shellock.

PMID- 22151818
TI  - Response to henderson et Al. "Prevention of mechanical failures in implanted
      spinal cord stimulation systems".

PMID- 22151819
TI  - Pressure ulcers induced by a spinal catheter.

PMID- 22151820
TI  - Homoepitaxial regrowth habits of ZnO nanowire arrays.
AB  - Synthetic regrowth of ZnO nanowires [NWs] under a similar chemical vapor
      transport and condensation [CVTC] process can produce abundant ZnO nanostructures
      which are not possible by a single CVTC step. In this work, we report three
      different regrowth modes of ZnO NWs: axial growth, radial growth, and both
      directions. The different growth modes seem to be determined by the properties of
      initial ZnO NW templates. By varying the growth parameters in the first-step CVTC
      process, ZnO nanostructures (e.g., nanoantenna) with drastically different
      morphologies can be obtained with distinct photoluminescence properties. The
      results have implications in guiding the rational synthesis of various ZnO NW
      heterostructures.

PMID- 22151821
TI  - Metabolism, gas exchange, and acid-base balance of giant salamanders.
AB  - The giant salamanders are aquatic and paedomorphic urodeles including the genera
      Andrias and Cryptobranchus (Cryptobranchidae), Amphiuma (Amphiumidae), Siren
      (Sirenidae), and Necturus (Proteidae, of which only N. maculosus is considered 'a
      giant'). Species in the genera Cryptobranchus and Necturus are considered aquatic
      salamanders well adapted for breathing water, poorly adapted for breathing air,
      and with limited abilities to compensate acid-base disturbances. As such, they
      are water-breathing animals with a somewhat fish-like respiratory and acid-base
      physiology, whose habitat selection is limited to waters that do not typically
      become hypoxic or hypercarbic (although this assertion has been questioned for N.
      maculosus). Siren and Amphiuma species, by contrast, are dependent upon air
      breathing, have excellent lungs, inefficient (Siren) or no (Amphiuma) gills, and
      are obligate air-breathers with an acid-base status more similar to that of
      terrestrial tetrapods. As such, they can be considered to be air-breathing
      animals that live in water. Their response to the aquatic hypercarbia that they
      often encounter is to maintain intracellular pH (pH(i) ) and abandon
      extracellular pH regulation, a process that has been referred to as preferential
      pH(i)  regulation. The acid-base status of some present-day tropical air
      breathing fishes, and of Siren and Amphiuma, suggests that the acid-base
      transition from a low PCO(2) -low [] system typical of water-breathing fishes to
      the high PCO(2) -high [] systems of terrestrial tetrapods may have been completed
      before emergence onto land, and likely occurred in habitats that were typically
      both hypoxic and hypercarbic.

PMID- 22151822
TI  - Factors associated with severity on admission and in-hospital mortality after
      primary intracerebral hemorrhage in China.
AB  - BACKGROUND AND PURPOSE: Of the stroke types, intracerebral hemorrhage is the most
      debilitating and fatal. The aim of the current study was to determine factors
      that influence the severity and in-hospital mortality after primary intracerebral
      hemorrhage. METHODS: Data were collected retrospectively on 1268 patients with
      primary intracerebral hemorrhage admitted to stroke units at participating
      hospitals in Guangzhou between January 2005 and August 2008. Logistic regression
      analysis was used to determine factors associated with severity on admission and
      in-hospital mortality. RESULTS: Of the 1268 patients, 20.4% were reported to have
      a severe stroke on admission, and the in-hospital mortality rate was 12.5%.
      Severity on admission was strongly associated with Glasgow Coma Scale score on
      admission (odds ratio = 0.89, 95% confidence interval 0.85-0.94) and hematoma
      location. Notably, basal ganglia hemorrhages were associated with increased
      severity (odds ratio = 1.40, 95% confidence interval 1.03-1.90), and cerebellar
      hemorrhages were associated with reduced severity (odds ratio = 0.29, 95%
      confidence interval 0.10-0.84). In-hospital mortality was not only correlated
      with Glasgow Coma Scale score on admission (odds ratio = 0.79, 95% confidence
      interval 0.74-0.84) and basal ganglia location (odds ratio = 0.47, 95% confidence
      interval 0.26-0.83), but also with dysnatremia (odds ratio = 1.91, 95% confidence
      interval 1.08-3.40) and comorbidities such as upper gastrointestinal hemorrhage
      (odds ratio = 2.28, 95% confidence interval 1.33-3.91), pneumonia (odds ratio =
      3.50, 95% confidence interval 2.17-5.63), urinary incontinence (odds ratio =
      2.22, 95% confidence interval 1.40-3.51), and renal dysfunction (odds ratio =
      2.28, 95% confidence interval 1.42-3.65). CONCLUSION: Glasgow Coma Scale score
      and hematoma locations were independently associated with severity on admission
      and in-hospital mortality after primary intracerebral hemorrhage. The study also
      highlights the deleterious effect of comorbidities on in-hospital mortality
      following primary intracerebral hemorrhage in China.

PMID- 22151823
TI  - A linear classifier based on entity recognition tools and a statistical approach
      to method extraction in the protein-protein interaction literature.
AB  - BACKGROUND: We participated, as Team 81, in the Article Classification and the
      Interaction Method subtasks (ACT and IMT, respectively) of the Protein-Protein
      Interaction task of the BioCreative III Challenge. For the ACT, we pursued an
      extensive testing of available Named Entity Recognition and dictionary tools, and
      used the most promising ones to extend our Variable Trigonometric Threshold
      linear classifier. Our main goal was to exploit the power of available named
      entity recognition and dictionary tools to aid in the classification of documents
      relevant to Protein-Protein Interaction (PPI). For the IMT, we focused on
      obtaining evidence in support of the interaction methods used, rather than on
      tagging the document with the method identifiers. We experimented with a
      primarily statistical approach, as opposed to employing a deeper natural language
      processing strategy. In a nutshell, we exploited classifiers, simple pattern
      matching for potential PPI methods within sentences, and ranking of candidate
      matches using statistical considerations. Finally, we also studied the benefits
      of integrating the method extraction approach that we have used for the IMT into
      the ACT pipeline. RESULTS: For the ACT, our linear article classifier leads to a
      ranking and classification performance significantly higher than all the reported
      submissions to the challenge in terms of Area Under the Interpolated Precision
      and Recall Curve, Mathew's Correlation Coefficient, and F-Score. We observe that
      the most useful Named Entity Recognition and Dictionary tools for classification
      of articles relevant to protein-protein interaction are: ABNER, NLPROT, OSCAR 3
      and the PSI-MI ontology. For the IMT, our results are comparable to those of
      other systems, which took very different approaches. While the performance is not
      very high, we focus on providing evidence for potential interaction detection
      methods. A significant majority of the evidence sentences, as evaluated by
      independent annotators, are relevant to PPI detection methods. CONCLUSIONS: For
      the ACT, we show that the use of named entity recognition tools leads to a
      substantial improvement in the ranking and classification of articles relevant to
      protein-protein interaction. Thus, we show that our substantially expanded linear
      classifier is a very competitive classifier in this domain. Moreover, this
      classifier produces interpretable surfaces that can be understood as "rules" for
      human understanding of the classification. We also provide evidence supporting
      certain named entity recognition tools as beneficial for protein-interaction
      article classification, or demonstrating that some of the tools are not
      beneficial for the task. In terms of the IMT task, in contrast to other
      participants, our approach focused on identifying sentences that are likely to
      bear evidence for the application of a PPI detection method, rather than on
      classifying a document as relevant to a method. As BioCreative III did not
      perform an evaluation of the evidence provided by the system, we have conducted a
      separate assessment, where multiple independent annotators manually evaluated the
      evidence produced by one of our runs. Preliminary results from this experiment
      are reported here and suggest that the majority of the evaluators agree that our
      tool is indeed effective in detecting relevant evidence for PPI detection
      methods. Regarding the integration of both tasks, we note that the time required
      for running each pipeline is realistic within a curation effort, and that we can,
      without compromising the quality of the output, reduce the time necessary to
      extract entities from text for the ACT pipeline by pre-selecting candidate
      relevant text using the IMT pipeline.

PMID- 22151824
TI  - Revision of occipital nerve stimulator leads: technical note of two techniques.
AB  - OBJECTIVE: Occipital nerve stimulation can be effective therapy for recalcitrant
      headache disorders. Lead migration remains the primary technical adverse event
      associated with this therapy. Revision surgery for occipital nerve stimulator
      leads sometimes requires exposure of all components including internal pulse
      generator, extension cables, connectors, and leads with multiple incisions.
      However, minimizing the invasiveness of revision surgery reduces the time,
      infection risk, and discomfort associated with the procedure. We describe two
      techniques that attempt to minimize the extent of revision surgery necessary for
      lead migration. MATERIALS AND METHODS: We describe two minimally invasive
      revision techniques. One uses a 14-gauge Tuohy needle converted to a slotted
      needle. The other uses a standard Tuohy needle inserted subcutaneously into the
      anchor site along the desired course of the lead. RESULTS: Both techniques allow
      replacement of a migrated occipital nerve stimulator lead while eliminating the
      need to access connector or battery sites with multiple incisions. CONCLUSIONS:  
      When migration occurs, the techniques described can simplify lead revision while
      minimizing the invasiveness of the procedure.

PMID- 22151825
TI  - Tissue expression of squamous cellular carcinoma antigen and Ki67 in
      hepatocellular carcinoma-correlation with prognosis: a historical prospective
      study.
AB  - BACKGROUND: Squamous cellular carcinoma antigen (SCCA) is overexpressed in
      hepatocellular carcinoma (HCC) tissue and in sera of HCC patients. Our aim was to
      assess hepatic SCCA immunostaining in a series of HCCs and to correlate its
      presence with cell proliferation, apoptosis and clinical outcome. METHODS: Sixty
      one HCC patients were included. Liver specimens were obtained either by biopsy (n
      = 17) or surgically (resection 27, transplantation 17). Immunostaining for AFP,
      Ki-67, SCCA and TUNEL assay were performed. RESULTS: SCCA staining was detected
      in 83.6% of specimens. A statistical significant correlation was found between
      negative SCCA staining and mortality (p = 0.026) and a higher immunostaining
      score for Ki67 (p = 0.017). Positive SCCA staining was associated with well and
      moderate differentiated tumors (p = 0.022). Using multiple logistic regression
      analysis, Ki67 and TUNEL assay were found to be significant independent
      predictors of negative SCCA immunostaining. The area under the receiver operator
      characteristic curve was 0.87. Kaplan-Meier survival analysis revealed a
      significant difference between the patient group with positive versus negative
      SCCA immunostaining relating to survival time (p = 0.0106). Cox proportional
      hazard regression analysis demonstrated that Ki67 immunostaining and liver
      transplantation or resection were independently associated with mortality.
      CONCLUSIONS: SCCA is overexpressed in HCC. SCCA status is associated with cell
      proliferation, apoptosis and survival. SCCA and Ki67 staining can predict
      survival. Our study results support a potential association of negative SCCA
      expression with other markers of poor outcome in HCC. More studies are needed to
      clarify the role of SCCA in HCC and expand the knowledge of the SCCA antigen in
      HCC patients.

PMID- 22151827
TI  - Clinical features, anatomical and visual outcomes, and prognostic factors in
      closed globe injuries presenting with no light perception: Eye Injury Vitrectomy
      Study.

PMID- 22151826
TI  - Feasibility of prolonged continuous glucose monitoring in toddlers with type 1
      diabetes.
AB  - OBJECTIVE: To examine the feasibility of continuous glucose monitoring (CGM) use
      in very young children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS:
      Twenty-three children less than 4 yr of age with T1D were provided with a
      FreeStyle Navigator((r)) (n = 21) or a Paradigm((r)) (n = 2) CGM device. At
      baseline, mean age was 3.0 +/- 0.8 yr, mean hemoglobin A1c (HbA1c) was 8.0 +/-
      0.8%, 10 were using an insulin pump and 13 were on multiple daily injections. CGM
      use was evaluated over a 6-month period. RESULTS: Three children dropped out of
      the study before the end of 6 months. Among the 20 children who completed 6
      months of follow-up, CGM use in month 6 was >=6 d/wk in 9 (45%), 4 <= 6 d/wk in 2
      (10%), and <4 d/wk in 9 (45%). Skin reactions were minimal. Although there was no
      detectable change in mean HbA1c between baseline and 6 months (7.9 and 8.0%,
      respectively), there was a high degree of parental satisfaction with CGM as
      measured on the CGM satisfaction scale questionnaire. A high percentage of
      glucose values were in the hyperglycemic range, and biochemical hypoglycemia was
      infrequent. CONCLUSION: More than 40% of very young children were able to safely
      use CGM on a near-daily basis after 6 months. CGM demonstrated frequent
      hyperglycemic excursions, with a large variability in glucose readings. Although
      improvement in glycemic control was not detected in the group as a whole,
      parental satisfaction with CGM was high.

PMID- 22151828
TI  - Pharmacokinetics of clindamycin in the plasma and dialysate after intraperitoneal
      administration of clindamycin phosphoester to patients on continuous ambulatory
      peritoneal dialysis: an open-label, prospective, single-dose, two-institution
      study.
AB  - We evaluated the pharmacokinetics of clindamycin and the dose of clindamycin
      phosphate necessary to treat peritonitis after intraperitoneal administration of
      clindamycin phosphate to patients on continuous ambulatory peritoneal dialysis
      (CAPD). This was an open-label, prospective, single-dose study conducted at the
      two levels of institutional clinical care in South Korea. Twelve patients (six
      men and six women; all older than 25 years), mean CAPD duration of 38.2 months
      with various origins without peritonitis, received 600 mg clindamycin phosphate
      mixed with only the first 2-L dialysate (1.5% dextrose). The 1.5%, 1.5%, 2.5% and
      1.5% dextrose dialysates were serially exchanged every 6 hr. If patients were non
      anuric, 24-hr urine samples were also collected. Clindamycin phosphate was
      incompletely activated to clindamycin in the dialysate. The clindamycin
      concentration in the dialysate was greater than the effective concentration (5
      MUg/mL) at 6.87 MUg/mL up to 6 hr. So, 600 mg clindamycin phosphate per every 6
      hr dialysate is effective for treatment of peritonitis. It has been reported that
      the clindamycin concentrations in the dialysate may be higher in CAPD patients
      with peritonitis. Thus, we can expect that intraperitoneal administration of <600
      mg clindamycin phosphate per every 6 hr dialysate could be maintained over 5
      MUg/mL in patients with peritonitis. The transfer of clindamycin was
      unidirectional from the dialysate to the plasma.

PMID- 22151829
TI  - Can non-invasive assessment of liver fibrosis replace liver biopsy?
AB  - Transient elastgraphy, acoustic radiation force impulse and real-time
      elastography are the methods with very good or excellent diagnostic accuracy for
      the assessment of liver fibrosis stage. They do not provide the information on
      inflammatory activity, steatosis, iron deposition or other findings derived from
      liver biopsy. Even on account of fibrosis stage, these non-invasive methods do
      not give us the estimation completely corresponding to that of liver biopsy.
      However they provide us useful clinical information that liver biopsy has been
      providing us, such as appropriate time to start antiviral therapy, prediction of
      response to antiviral therapy, evaluation of effects of antiviral therapy,
      assessment of natural course of hepatitis and estimation of prognosis of
      hepatitis. Recently non-invasive methods for assessment of inflammatory activity,
      steatosis and iron deposition in the liver have been developed. Thus in the near
      future, non-invasive methods will replace liver biopsy.

PMID- 22151830
TI  - Induction of cytotoxicity of Pelagia noctiluca venom causes reactive oxygen
      species generation, lipid peroxydation induction and DNA damage in human colon
      cancer cells.
AB  - BACKGROUND: The long-lasting and abundant blooming of Pelagia noctiluca in
      Tunisian coastal waters compromises both touristic and fishing activities and
      causes substantial economic losses. Determining their molecular mode of action
      is, important in order to limit or prevent the subsequent damages. Thus, the aim
      of the present study was to investigate the propensity of Pelagia noctiluca venom
      to cause oxidative damage in HCT 116 cells and its associated genotoxic effects.
      RESULTS: Our results indicated an overproduction of ROS, an induction of catalase
      activity and an increase of MDA generation. We looked for DNA fragmentation by
      means of the comet assay. Results indicated that venom of Pelagia noctiluca
      induced DNA fragmentation. SDS-PAGE analysis of Pelagia noctiluca venom revealed
      at least 15 protein bands of molecular weights ranging from 4 to 120 kDa.
      CONCLUSION: Oxidative damage may be an initiating event and contributes, in part,
      to the mechanism of toxicity of Pelagia noctiluca venom.

PMID- 22151831
TI  - Origin and evolution of gene families in Bacteria and Archaea.
AB  - BACKGROUND: Comparison of complete genomes of Bacteria and Archaea shows that
      gene content varies considerably and that genomes evolve quite rapidly via gene
      duplication and deletion and horizontal gene transfer. We analyze a diverse set
      of 92 Bacteria and 79 Archaea in order to investigate the processes governing the
      origin and evolution of families of related genes within genomes. RESULTS: Genes
      were clustered into related groups using similarity criteria derived from BLAST.
      Most clusters contained genes from only one or a small number of genomes, and
      relatively few core clusters were found that spanned all genomes. Gene clusters
      found in larger numbers of genomes tended to have larger numbers of genes per
      genome; however, clusters with unusually large numbers of genes per genome were
      found among both narrowly and widely distributed clusters. Larger genomes were
      found to have larger mean gene family sizes and a greater proportion of families
      of very large size. We used a model of birth, death, and innovation to predict
      the distribution of gene family sizes. The key parameter is r, the ratio of
      duplications to deletions. It was found that the model can give a good fit to the
      observed distribution only if there are several classes of genes with different
      values of r. The preferred model in most cases had three classes of genes.
      CONCLUSIONS: There appears to be a rapid rate of origination of new gene families
      within individual genomes. Most of these gene families are deleted before they
      spread to large numbers of genomes, which suggests that they may not be generally
      beneficial to the organisms. The family size distribution is best described by a
      large fraction of families that tend to have only one or two genes and a small
      fraction of families of multi-copy genes that are highly prone to duplication.
      Larger families occur more frequently in larger genomes, indicating higher r in
      these genomes, possibly due to a greater tolerance for non-beneficial gene
      duplicates. The smallest genomes contain very few multi-copy families, suggesting
      a high rate of deletion of all but the most beneficial genes in these genomes.

PMID- 22151832
TI  - Basic fibroblast growth factor and tumour necrosis factor alpha in vitiligo and
      other hypopigmented disorders: suggestive possible therapeutic targets.
AB  - BACKGROUND: In healthy skin, there is a molecular microenvironment that favours
      the survival of melanocytes and regulates their function. Keratinocytes
      synthesize and secrete several cytokines that have stimulatory and inhibitory
      effects on melanocytes. AIM OF THE WORK: This work was conducted to evaluate the
      expression of basic fibroblast growth factor (bFGF) and tumour necrosis factor
      alpha (TNF-alpha) mRNA levels in lesional skin of vitiligo, hypopigmented mycosis
      fungoides and hypopigmented tinea versicolor. PATIENTS AND METHODS: Forty eight
      patients (25 vitiligo, 14 hypopigmented mycosis fungoides, 9 hypopigmented tinea
      versicolor) and 10 healthy controls were included. A 4 mm punch skin biopsy was
      taken from lesional skin of patients, and the normal skin of controls for
      quantitative PCR examination of TNF-alpha and bFGF mRNA. RESULTS: The level of
      TNF-alpha mRNA in lesional skin of the three studied disorders was significantly
      higher than in the control group, while the level of bFGF mRNA was significantly
      lower in lesional skin of the three diseases than the control skin. A significant
      inverse correlation was demonstrated between the mRNA levels of the two studied
      cytokines in vitiligo and hypopigmented MF lesions. CONCLUSION: The study's
      findings demonstrate that the studied hypopigmented (vitiligo, hypopigmented MF,
      hypopigmented TV) disorders show similar changes in their cutaneous
      microenvironment with increased TNF-alpha and decreased bFGF mRNA expression.
      This cytokine microenvironment change may be implicated in the pigment loss and
      hence these cytokines may have future therapeutic implications.

PMID- 22151833
TI  - Effects of vaginal hysterectomy on anorectal sensorimotor functions--a
      prospective study.
AB  - BACKGROUND: While bowel and bladder dysfunction are recognized consequences of a
      radical hysterectomy, the effects of a simple hysterectomy on anorectal
      sensorimotor functions, particularly rectal sensation, vary among studies and the
      effects on rectal compliance remain unknown. Our aims were to prospectively
      evaluate anorectal sensorimotor functions before and after a hysterectomy.
      METHODS: Anal pressures, rectal compliance, capacity, sensation, and bowel
      symptoms were assessed before, at 2 months, and at 1 year after a simple vaginal
      hysterectomy for benign indications in 19 patients. Rectal staircase (0-44 mmHg,
      4-mmHg steps), ramp (0-200 mL at 50, 200 and 600 mL min(-1)) and phasic
      distentions (8, 16, and 24 mmHg above operating pressure) were performed. KEY
      RESULTS: Anal resting (63 +/- 4 before, 56 +/- 4 mmHg after) and squeeze
      pressures (124 +/- 12 before, 124 +/- 12 mmHg after), rectal compliance and
      capacity (285 +/- 12 before, 290 +/- 11 mL 1 year after), and perception of
      phasic distentions were not different before vs after a hysterectomy. Sensory
      thresholds for first sensation and the desire to defecate were also not
      different, but pressure and volume thresholds for urgency were somewhat greater
      (Hazard ratio = 0.7, 95% CI [0.5, 1.0]) 1 year after (vs before) a hysterectomy.
      Rectal pressures were higher (P < 0.0001) during fast compared with slow ramp
      distention; this rate effect was greater at 1 year after a hysterectomy,
      particularly at 100 mL (P = 0.04). CONCLUSIONS & INFERENCES: A simple vaginal
      hysterectomy has relatively modest effects (i.e., somewhat reduced rectal urgency
      and increased stiffness during rapid distention) on rectal sensorimotor
      functions.

PMID- 22151835
TI  - Frontiers of Retrovirology 2011, Amsterdam, The Netherlands, 3-5 October 2011.
      Meeting Abstracts.

PMID- 22151834
TI  - The Pap smear screening as an occasion for smoking cessation and physical
      activity counselling: baseline characteristics of women involved in the SPRINT
      randomized controlled trial.
AB  - BACKGROUND: Gender-specific smoking cessation strategies have rarely been
      developed. Evidence of effectiveness of physical activity (PA) promotion and
      intervention in adjunct to smoking cessation programs is not strong. SPRINT study
      is a randomized controlled trial (RCT) designed to evaluate a counselling
      intervention on smoking cessation and PA delivered to women attending the Italian
      National Health System Cervical Cancer Screening Program. This paper presents
      study design and baseline characteristics of the study population.
      METHODS/DESIGN: Among women undergoing the Pap examination in three study centres
      (Florence, Turin, Mantua), participants were randomized to the smoking cessation
      counselling [S], the smoking cessation + PA counselling [S + PA], or the control
      [C] groups. The program under evaluation is a standard brief counselling on
      smoking cessation combined with a brief counselling on increasing PA, and was
      delivered in 2010. A questionnaire, administered before, after 6 months and 1
      year from the intervention, was used to track behavioural changes in tobacco use
      and PA, and to record cessation rates in participants. DISCUSSION: Out of the
      5,657 women undergoing the Pap examination, 1,100 participants (55% of smokers)
      were randomized in 1 of the 3 study groups (363 in the S, 366 in the S + PA and
      371 in the C groups). The three arms did not differ on any demographic, PA, or
      tobacco-use characteristics. Recruited smokers were older, less educated than non
      participant women, more motivated to quit (33% vs.9% in the Preparation stage, p
      < 0.001), smoked more cigarettes per day (12 vs.9, p < 0.001), and were more
      likely to have already done 1 or more quit attempts (64% vs.50%, p < 0.001). The
      approach of SPRINT study appeared suitable to enrol less educated women who
      usually smoke more and have more difficulties to quit. TRIAL REGISTRATION NUMBER:
      ISRCTN: ISRCTN52660565.

PMID- 22151836
TI  - Effects of mealtime insulin aspart and bedtime neutral protamine Hagedorn insulin
      on postprandial coagulation and fibrinolysis in patients with type 2 diabetes.
AB  - AIM: Acute hyperglycaemia induces coagulation activation in diabetes patients. We
      hypothesized that rapid-acting insulin has a beneficial postprandial effect on
      coagulation and fibrinolysis compared with intermediate-acting insulin because of
      its ability to lower postprandial hyperglycaemia. METHODS: This was tested in a
      parallel controlled study in well-controlled patients with type 2 diabetes
      assigned to bedtime neutral protamine Hagedorn (NPH) insulin (n = 41) or mealtime
      insulin aspart (n = 37). They were served standard diabetic meals for breakfast
      (8:00 hours) and lunch (12:00 hours). Blood samples were collected at 7:40 hours
      (fasting), 9:30, 11:30, 13:30 and 15:30 hours and analysed for glucose, activated
      factor VII (FVIIa), D-dimer, prothrombin fragment 1+2 (F1+2), tissue plasminogen
      activator antigen (t-PA) and plasminogen activator inhibitor activity (PAI).
      RESULTS: The postprandial glucose response differed significantly between insulin
      regimens with a postprandial increase on NPH insulin and a decrease on insulin
      aspart. There was a significant postprandial decrease in F1+2, PAI and t-PA, and
      no changes in FVIIa and D-dimer, on both insulin regimens, but with no
      differences between insulin treatment groups. CONCLUSIONS: The rapid-acting
      insulin analogue aspart and the intermediate-acting insulin NPH had similar
      postprandial effects on markers of coagulation activation and fibrinolysis
      despite different effects on postprandial glucose response.

PMID- 22151837
TI  - Neuroprotective effects of a new skin care formulation following ultraviolet
      exposure.
AB  - BACKGROUND: Chronic ultraviolet (UV) exposure is a major environmental factor
      involved in extrinsic skin ageing (photo-ageing). Skin nerve fibres are
      significantly reduced in number following UV irradiation and new skincare
      compounds with neuroprotective effects are thus highly warranted. OBJECTIVES: We
      developed a new skincare formulation from a plant extract and evaluated its
      neuroprotective effects of ex vivo UV irradiation. MATERIALS AND METHODS: The new
      skincare emulsion was formulated from Echinacea purpurea extract and was enriched
      with antioxidants (patent no. PROV020110087075). Skin samples were obtained from
      20 healthy patients enrolled for plastic surgery and were immediately treated
      with placebo (SPF 15) or test emulsions. Skin samples were exposed to UVA and UVB
      for 60 min. Nerve fibres were identified by immunofluorescence using a monoclonal
      antibody, anti-human CD56. Cell damage was quantified by image analysis. RESULTS:
      UVA and UVB significantly reduced (40-60%) densities of nerve endings in control
      samples treated with placebo (P < 0.001). Samples treated with test emulsion
      completely blocked UV-related effects on skin nerve endings. These
      neuroprotective effects were similarly observed regardless of age or tissue
      analysed (breast versus abdomen). CONCLUSIONS: Our new skincare formulation
      obtained from E. purpurea provides important neuroprotective effects of UV
      irradiation and could be used together with SPFs to prevent chronic deleterious
      effects of solar exposure.

PMID- 22151838
TI  - Transformation by stealth: the retargeting of home care services in Finland.
AB  - This paper analyses the trends and changes that home care services for older
      people have undergone during the last two decades in Finland. The data used come
      from national social care statistics, covering the time period from 1990-2010.
      The results show that, in contrast to many other European nations that have
      expanded their home care provisions, the coverage levels in Finland have dropped
      dramatically during this period. Those with the highest needs do receive
      increased amounts of support, but others have become excluded from publicly
      funded home care provisions and often need to rely on family members. In most
      localities, public service provision is focused on personal care, and no longer
      covers household tasks. This major change of the character of the service is
      connected to three other recent trends that structure current provisions: the
      amalgamation of home-based social and healthcare services, the marketisation and
      emerging privatisation of care and the integration of informal family care into
      the formal care system. Overall, the changes represent weakening defamilisation,
      that is, decreasing public responsibility for the needs of many older people and,
      correspondingly, an increasing reliance on family carers. This full-scale
      transformation of home care has taken place without any real policy debate or
      major modification of legislation. No actual decision was ever made to thoroughly
      alter the character of home care in Finland: the transformation happened by
      stealth.

PMID- 22151839
TI  - Evaluation of human first trimester decidual and telomerase-transformed
      endometrial stromal cells as model systems of in vitro decidualization.
AB  - BACKGROUND: Decidualization, the differentiation process of maternal uterine
      stromal cells into secretory decidual cells, is a prerequisite for successful
      implantation and progression of pregnancy. For in vitro differentiation mostly
      primary human endometrial stromal cells (HESC) isolated from uterine samples
      after hysterectomy for benign gynaecological diseases are utilised. However, a
      continuous supply of endometrial tissue is often lacking. Hence, we analysed
      whether cultivated human decidual stromal cells (HDSC) prepared from first
      trimester pregnancy terminations may represent an alternative model system for in
      vitro decidualization. Moreover, based on the expression of critical marker genes
      these cells were compared to a previously established endometrial stromal cell
      line during in vitro differentiation. METHODS: HDSC isolated from decidual tissue
      attached to first trimester placentae, and telomerase-transformed human
      endometrial stromal cells (THESC) were characterised by immunofluorescence and
      differentiated in vitro using either cyclic adenosine monophosphate (cAMP) and/or
      estrogen (E2)/progesterone (P4). Proliferation was measured by analyzing
      cumulative cell numbers. Expression of mRNAs encoding progesterone receptor (PR),
      prolactin (PRL), insulin-like growth factor binding protein-1 (IGFBP1), and
      Dickkopf-1 (DKK1) was evaluated using quantitative PCR after 3, 6, 9 and 12 days
      of in vitro differentiation. PRL and IGFBP-1 protein expression was investigated
      by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively.
      Furthermore, forkhead box O1A (FOXO1A), a critical transcription factor in
      decidualization, was analysed by immunofluorescence and Western blotting at two
      different time points of differentiation. RESULTS: Treatment with cAMP provoked
      morphological changes and growth arrest of THESC and HDSC, the latter showing
      loss of cells after 6 days of treatment. E2P4 stimulation did neither affect cell
      morphology nor proliferation of THESC and HDSC. Upon cAMP stimulation PR mRNA was
      suppressed in HDSC but not in THESC, whereas E2P4 did not alter transcript levels
      in both cell types. Protein expression of PR-A and PR-B was detectable in HDSC
      and diminished under cAMP, whereas THESC failed to produce the nuclear receptors.
      Supplementation of cAMP induced mRNA and protein expression of PRL and IGFBP-1 in
      both cell types at day 3, 6, 9, and 12 of treatment. In HDSC stimulation with
      E2P4 increased PRL and IGFBP-1 mRNA and protein production, whereas hormone
      treatment did not induce the two factors in THESC. E2P4 increased DKK1 mRNA at
      all time points in HDSC and cAMP provoked induction at day 9 and 12 of
      differentiation. In contrast, cAMP suppressed DKK1 mRNA in THESC, whereas E2P4
      was ineffective. In both cell types combined treatments with cAMP and E2P4
      provoked higher expression levels of PRL and IGFBP1 mRNA and protein as compared
      to cAMP stimulation alone. FOXO1A protein and its nuclear abundance were
      increased by cAMP in both cell types. However, reduction of its nuclear
      localisation upon E2P4 treatment could only be observed in HDSC. CONCLUSION: Both
      HDSC and THESC may represent suitable model systems for cAMP-dependent in vitro
      decidualization. Since cAMP decreases cell viability of HDSC after 6 days of
      incubation, this substance should be preferentially used in short-term
      experiments. Progesterone treatment of THESC might not be applicable since these
      cells lack progesterone response and PR protein. In contrast, stimulation of PR
      expressing HDSC with E2P4 or cAMP/E2P4 may represent an appropriate protocol for
      human in vitro decidualization inducing and maintaining expression of critical
      marker genes in a time-dependent manner.

PMID- 22151840
TI  - Study of the efficacy of antimalarial drugs delivered inside targeted
      immunoliposomal nanovectors.
AB  - Paul Ehrlich's dream of a 'magic bullet' that would specifically destroy
      invading microbes is now a major aspect of clinical medicine. However, a century
      later, the implementation of this medical holy grail continues being a challenge
      in three main fronts: identifying the right molecular or cellular targets for a
      particular disease, having a drug that is effective against it, and finding a
      strategy for the efficient delivery of sufficient amounts of the drug in an
      active state exclusively to the selected targets. In a previous work, we
      engineered an immunoliposomal nanovector for the targeted delivery of its
      contents exclusively to Plasmodium falciparum-infected red blood cells [pRBCs].
      In preliminary assays, the antimalarial drug chloroquine showed improved efficacy
      when delivered inside immunoliposomes targeted with the pRBC-specific monoclonal
      antibody BM1234. Because difficulties in determining the exact concentration of
      the drug due to its low amounts prevented an accurate estimation of the
      nanovector performance, here, we have developed an HPLC-based method for the
      precise determination of the concentrations in the liposomal preparations of
      chloroquine and of a second antimalarial drug, fosmidomycin. The results obtained
      indicate that immunoliposome encapsulation of chloroquine and fosmidomycin
      improves by tenfold the efficacy of antimalarial drugs. The targeting antibody
      used binds preferentially to pRBCs containing late maturation stages of the
      parasite. In accordance with this observation, the best performing
      immunoliposomes are those added to Plasmodium cultures having a larger number of
      late form-containing pRBCs. An average of five antibody molecules per liposome
      significantly improves in cell cultures the performance of immunoliposomes over
      non-functionalized liposomes as drug delivery vessels. Increasing the number of
      antibodies on the liposome surface correspondingly increases performance, with a
      reduction of 50% parasitemia achieved with immunoliposomes encapsulating 4 nM
      chloroquine and bearing an estimated 250 BM1234 units. The nanovector prototype
      described here can be a valuable platform amenable to modification and
      improvement with the objective of designing a nanostructure adequate to enter the
      preclinical pipeline as a new antimalarial therapy.

PMID- 22151841
TI  - Comparison of published orthopaedic trauma trials following registration in
      Clinicaltrials.gov.
AB  - BACKGROUND: After the Food and Drug Administration Modernization Act of 1997, the
      registration of all clinical trials became mandatory prior to publication. Our
      primary objective was to determine publication rates for orthopaedic trauma
      trials registered with ClinicalTrials.gov. We further evaluated methodological
      consistency between registration and publication. METHODS: We searched Clinical
      Trials.gov for all trials related to orthopaedic trauma. We excluded active
      trials and trials not completed by July 2009, and performed a systematic search
      for publications resulting from registered closed trials. Information regarding
      primary and secondary outcomes, intervention, study sponsors, and sample size
      were extracted from registrations and publications. RESULTS: Of 130 closed
      trials, 37 eligible trials resulted in 16 publications (43.2%). We found no
      significant differences in publication rates between funding sources for industry
      sponsored studies and nongovernment/nonindustry sponsored studies (p > 0.05).
      About half the trials (45%) did not include the NCT ID in the publication. Two
      (10%) publications had major changes to the primary outcome measure and ten
      (52.6%) to sample size. CONCLUSIONS: Registration of orthopaedic trauma trials
      does not consistently result in publication. When trials are registered, many do
      not cite NCT ID in the publication. Furthermore, changes that are not reflected
      in the registry of the trial are frequently made to the final publication.

PMID- 22151842
TI  - Abstracts of the 27th Patient Classification Systems International (PCSI) Working
      Conference. Montreal, Canada. October 19-22, 2011.

PMID- 22151843
TI  - Implications of the placebo response for interventional pain specialists.

PMID- 22151844
TI  - Implantation of the synergy pulse generator in the gluteal area: surgical
      technique.
AB  - We describe a technique for the safe and aesthetically pleasing implantation of
      the Synergy pulse generator in the posterior iliac region for spinal cord
      stimulation. The technique can be applied to both thin and obese patients.

PMID- 22151845
TI  - Spinal cord stimulation: cost-benefit study.

PMID- 22151846
TI  - Four Year Follow-up of Dual Electrode Spinal Cord Stimulation for Chronic Pain.
AB  - This paper reports on 80 patients using dual electrode, spinal cord stimulation
      (SCS) over a four-year period Implant status, stimulation mode, anode-cathode
      configuration (array), cathode position, paresthesia overlap, explantation rates,
      complications, Visual Analog Scores (VAS), and overall satisfaction were examined
      in patients implanted with dual 8 contact, staggered, percutaneous electrodes.
      All patients had undergone implantation for chronic axial and extremity pain
      [e.g., Failed Back Surgery Syndrome (FBSS), Complex Regional Pain Syndrome
      (CRPS)]. Outcomes were evaluated in view of our previous reports in this same
      group at 24 and 30 months (1,2). Data was collected by a disinterested third
      party. At 48 months, 18 of the original 80 patients were lost to follow-up. Of
      the 62 patients contacted, 33 remained implanted and 29 (47%) had been explanted.
      After an average evaluation of 85 arrays (PainDoc, Advanced Neuromodulation
      Systems, Plano, Texas), 88% of patients reported using one or two "best" arrays
      (bipolar or guarded tripolar) to maintain favorable paresthesia overlap (89%),
      VAS reduction (8.1 to 4.9), and overall patient satisfaction (63%). These arrays
      were most commonly positioned about the physiologic midline of the COL3-4
      vertebral segments for upper extremity pain, and the T9-10 vertebral segments for
      low back and lower extremity pain. In contrast to our initial reports where
      essentially all patients preferred more than two arrays to maintain "best"
      paresthesia overlap and outcome, only 12% of these same patients maintained this
      trend in this long-term follow-up study. The arrays most commonly selected long
      term as the "best" ones (88% of all electrodes) were narrow (adjacent contact)
      bipoles and guarded cathode tripoles (< 8 contacts). Thirty-five percent of
      patients with thoracic implants achieved paresthesia in the low back at 48
      months. Explantation rates and overall patient satisfaction were significantly
      affected by painful radio frequency (RF) antenna coupling. This data supports the
      efficacy of dual electrodes in optimizing long-term SCS paresthesia overlap and
      complex pain outcomes.

PMID- 22151847
TI  - Making a case for programmable pumps over fixed rate pumps for the management of
      fluctuations in chronic pain and spasticity: a literature review.
AB  - This paper reviews data supporting the existence of individual, predictable, and
      unpredictable fluctuations in the severity of chronic pain and spasticity. It
      also evaluates what is known on the use of implantable programmable drug delivery
      systems for the management of predictable fluctuations in pain and spasticity. In
      addition to fixed rate infusion pumps, programmable drug delivery systems have
      been developed over the past 20 years for the management of predictable pain or
      spasticity fluctuations. The published literature on experimental and clinical
      studies of those topics is reviewed and evaluated. Programmable drug delivery
      systems can tailor dosing to a patient's individual pattern of symptoms,
      providing more medication during peak intensity of symptoms and less medication
      when symptoms are reduced. Fluctuations in either pain or spasticity are
      difficult to predict precisely, and therefore even programmable pumps cannot
      administer the appropriate amount of medication at any particular time. Ideally,
      the patient should be able to treat unpredictable fluctuations in symptoms, and a
      combination of patient controlled analgesia (PCA) with programmable drug delivery
      systems is currently in development. The future management of unpredictable
      fluctuations in the intensity of chronic pain and spasticity was subjected to
      critical evaluation. There seems to be a general agreement on the clinical
      importance of these phenomena, but stronger evidence is needed for a widespread
      change in the current management of most chronic pain patients.

PMID- 22151848
TI  - A method for reducing the pocket complications of the internal infusion pumps in
      pediatric patients: a case report.
AB  - Internal infusion pumps are increasingly used as a safe method to deliver drugs
      in adult patients. However, a formal contraindication of this mode of therapy is
      the presence of a imbalance between the pump volume and the size of the abdominal
      wall as occurs in pediatric populations. We describe a method of implantation of
      an intrathecal infusion pump for baclofen therapy in a 10-year-old patient with
      cerebral palsy. Before the pump implantation we inserted a subcutaneous expander
      with a reservoir that was filled with saline solution every week. After three
      sessions, a pocket similar in size to an internal infusion pump was obtained. The
      result was a pump pocket with soft shaping and no edges that would not generate
      pressure sores or tissue tension after the pump insertion. This method could
      extend the use of internal infusion pumps in pediatric populations.

PMID- 22151849
TI  - Continuous intrathecal baclofen infusion delivered by a programmable pump for the
      treatment of severe spasticity following traumatic brain injury.
AB  - The aim of this study was to determine the efficacy and safety of intrathecal
      baclofen (ITB) delivered by a programmable pump for the chronic treatment of
      severe spasticity due to traumatic brain injury (TBI). Eight patients with severe
      spasticity following TBI, refractory to oral baclofen or who experienced
      intolerable side effects, were screened. The first five patients were enrolled in
      a research protocol that was approved by the Institutional Review Board for Human
      Research at Boston University Medical Center. The other three patients were
      evaluated after the FDA approved the therapy for spasticity of cerebral origin.
      Results showed that the mean Ashworth score for rigidity in the legs decreased
      from 4.4 preoperatively to 1.3 (p < 0.05) on ITB. In the arms, the Ashworth score
      decreased from 2.7 to 1.5 (p < 0.05). Reduction of spasticity resulted in
      improved levels of physical activity and locomotion and ease of care.
      Complications consisted of muscular hypotonia, areflexic bladder and urinary
      retention, erythema, and breakdown of the skin over the pump. Our results suggest
      that long-term intrathecal baclofen by an implanted programmable pump is a safe
      and effective method of treating severe intractable spasticity arising from
      traumatic brain injury.

PMID- 22151850
TI  - Continuous intrathecal infusion of a solution containing two drugs: calculation
      methods.
AB  - The calculation of the parameters of the pump is complicated for a mixture of two
      drugs in continuous intrathecal therapy with implantable and programmable pumps.
      It is important to determine the best proportion of drug solutions to obtain the
      desired clinical results and also to adapt their proportion to obtain the maximal
      volume of solution so that the time between two fillings is maximized. This paper
      proposes mathematical formulas that make easier and faster the calculation of the
      flow of the pump, the volume of each drug solution to be added to the pump, the
      concentration of each drug in the mixture, and the duration of the infusion.
      These values are determined from the desired quantity of each drug to be infused
      in 24 h, the concentration of each drug solution, and the volume of the
      reservoir. The calculated values cannot be directly applied because the syringes
      used to measure the volume of each drug solution have limited accuracy. It is
      necessary to round the volume of each drug solution and to hold their sum equal
      to the total volume of the reservoir. All the parameters are then recalculated,
      and the physician has to choose between several combinations of volumes.

PMID- 22151851
TI  - Cerebral palsy: results of surgical releases augmented with electrical
      stimulation: a case study.
AB  - The purpose of this case study was to evaluate a patient with diplegic cerebral
      palsy who underwent soft tissue lengthening augmented with intramuscular
      electrical stimulation. This is a prospective case study, pre- and post-test
      design. The patient underwent soft tissue lengthenings of the lower extremities,
      augmented with placement of intramuscular neuromuscular electrodes. Baseline, 4-,
      8-, and 12-month follow-up data were obtained which included range of motion,
      manual muscle strength testing, motion analysis, oxygen consumption, Gross Motor
      Function Measure, and Pediatric Evaluation of Disability Inventory. All measured
      parameters, except knee extensor strength, improved during the postoperative
      period (baseline to 4-month follow-up) and continued to improve during the
      rehabilitative period (4-12 month follow-up), despite no formal therapy or home
      exercise program during this period. We conclude that surgical releases augmented
      with electrical stimulation resulted in a satisfactory clinic outcome, and may
      offer a new approach to the treatment of patients with cerebral palsy.

PMID- 22151852
TI  - Length dependent potentiation in electrically stimulated human ankle dorsiflexor
      muscles.
AB  - The purpose of this study was to investigate the short-term history effect of a
      decreasing frequency train on force and the influence of joint angle on such
      effect in human dorsiflexor muscles. Six able-bodied and three spinal cord
      injured (SCI) subjects took part in the study. Their isometric left dorsiflexor
      muscles were stimulated with two-second bursts at three ankle joint positions and
      movements at the ankle were measured. Trains with constant stimulation
      frequencies (CSF: 50, 25, 20, 16, 12, 8 Hz) and with decreasing stimulation
      frequencies (DSF1,2) were used. Each DSF tetanus consisted of four 0.5 second
      bursts of different frequencies (DSF1: 50, 25, 16, 8 Hz; DSF2: 50, 20, 12, 8 Hz).
      To evaluate the effect of preceding higher stimulation frequencies (DSF), the
      average moment at corresponding time intervals in the DSF and CSF trials were
      compared for 25, 20, 16, 12, 8 Hz. Preceding higher stimulation frequencies
      caused increase of the moment elicited by a given frequency. This was true for
      all the subjects at dorsiflexed positions, but the effect is highly dependent on
      joint ankle. At plantar flexed positions moment enhancement was seen only in SCI
      subjects. We conclude that effects of joint angle as well as individual muscle
      properties should be taken into account when optimizing muscle force by means of
      frequency modulation.

PMID- 22151853
TI  - Compliance with focused antenatal care services: do health workers in rural
      Burkina Faso, Uganda and Tanzania perform all ANC procedures?
AB  - OBJECTIVE: To assess health workers' compliance with the procedures set in the
      focused antenatal care (ANC) guidelines in rural Uganda, Tanzania and Burkina
      Faso; to compare the compliance within and among the three study sites; and to
      appraise the logistic and supply of the respective health facilities (HF).
      METHODS: The cross-sectional study was conducted in the rural HF in three African
      countries. This descriptive observational study took place in HF in Nouna,
      Burkina Faso (5), Iganga, Uganda (6) and Rufiji, Tanzania (7). In total, 788 ANC
      sessions and service provisions were observed, the duration of each ANC service
      provision was calculated, and the infrastructures of the respective HF were
      assessed. RESULTS: Health workers in all HF performed most of the procedures but
      also omitted certain practices stipulated in the focused ANC guidelines. There
      was a substantial variation in provision of ANC services among HF within and
      among the country sites. The findings also revealed that the duration of first
      visits was <15 min and health workers spent even less time in subsequent visits
      in all three sites. Reagents for laboratory tests and drugs as outlined in the
      focus ANC guidelines were often out of stock in most facilities. CONCLUSION:
      Health workers in all three country sites failed to perform all procedures
      stipulated in the focused ANC guideline; this could not be always explained by
      the lack of supplies. It is crucial to point out the necessity of the core
      procedures of ANC repeatedly.

PMID- 22151854
TI  - Sequencing by ligation variation with endonuclease V digestion and deoxyinosine
      containing query oligonucleotides.
AB  - BACKGROUND: Sequencing-by-ligation (SBL) is one of several next-generation
      sequencing methods that has been developed for massive sequencing of DNA
      immobilized on arrayed beads (or other clonal amplicons). SBL has the advantage
      of being easy to implement and accessible to all because it can be performed with
      off-the-shelf reagents. However, SBL has the limitation of very short read
      lengths. RESULTS: To overcome the read length limitation, research groups have
      developed complex library preparation processes, which can be time-consuming,
      difficult, and result in low complexity libraries. Herein we describe a variation
      on traditional SBL protocols that extends the number of sequential bases that can
      be sequenced by using Endonuclease V to nick a query primer, thus leaving a
      ligatable end extended into the unknown sequence for further SBL cycles. To
      demonstrate the protocol, we constructed a known DNA sequence and utilized our
      SBL variation, cyclic SBL (cSBL), to resequence this region. Using our method, we
      were able to read thirteen contiguous bases in the 3' - 5' direction.
      CONCLUSIONS: Combining this read length with sequencing in the 5' - 3' direction
      would allow a read length of over twenty bases on a single tage. Implementing
      mate-paired tags and this SBL variation could enable > 95% coverage of the
      genome.

PMID- 22151855
TI  - Tissue-engineered provisional matrix as a novel approach to enhance diabetic
      wound healing.
AB  - Inherent pathologies associated with diabetic wound microenvironment including
      increased proteolysis, inflammatory dysregulation, and impaired
      neovascularization prevent timely resolution of chronic diabetic ulcers. It is
      hypothesized that augmentation of local wound microenvironment with a stable
      provisional matrix formed by proteolysis-resistant angiogenic peptide nanofibers
      (NFs) will create permissive environment for attenuated inflammation, enhanced
      neovascularization, and improved diabetic wound healing. Using murine excisional
      wound healing models, full-thickness dorsal skin wounds were treated with either
      NFs or control solutions (phosphate buffered saline; hyaluronic acid) and
      analyzed for morphology, inflammatory response, neovascularization, and
      biomechanical properties. NF treatment of diabetic wounds stimulated formation of
      a robust pro-angiogenic in situ tissue-engineered provisional matrix leading to a
      significant decrease in wound inflammatory cell infiltration and proinflammatory
      interleukin-6 levels, a significant increase in endothelial and endothelial
      progenitor cell infiltration, vascular endothelial growth factor levels, and
      neovascularization (day 7), as well as improved wound morphology, accelerated
      wound closure, and significantly stronger repair tissue (day 28). These results
      suggest that appropriate design of provisional matrix may compensate for some of
      the complex disruptions in diabetic wound microenvironment and provide missing
      cues to cells and direct in situ responses toward improved healing, which is
      promising for future development of new therapies for diabetic ulcers.

PMID- 22151856
TI  - Redesigning the ICU nursing discharge process: a quality improvement study.
AB  - PURPOSE: To evaluate the impact of a redesigned intensive care unit (ICU) nursing
      discharge process on ICU discharge delay, hospital mortality, and ICU readmission
      within 72 hours. METHODS: A quality improvement study using a time series design
      and statistical process control analysis was conducted in one Australian general
      ICU. The primary outcome measure was hours of discharge delay per patient
      discharged alive per month, measured for 15 months prior to, and for 12 months
      after the redesigned process was implemented. The redesign process included
      appointing a change agent to facilitate process improvement, developing a patient
      handover sheet, requesting ward staff to nominate an estimated transfer time, and
      designing a daily ICU discharge alert sheet that included an expected date of
      discharge. RESULTS: A total of 1,787 ICU discharges were included in this study,
      1,001 in the 15 months before and 786 in the 12 months after the implementation
      of the new discharge processes. There was no difference in in-hospital mortality
      after discharge from ICU or ICU readmission within 72 hours during the study
      period. However, process improvement was demonstrated by a reduction in the
      average patient discharge delay time of 3.2 hours (from 4.6 hour baseline to 1.0
      hours post-intervention). CONCLUSIONS: Involving both ward and ICU staff in the
      redesign process may have contributed to a shared situational awareness of the
      problems, which led to more timely and effective ICU discharge processes. The use
      of a change agent, whose ongoing role involved follow-up of patients discharged
      from ICU, may have helped to embed the new process into practice.

PMID- 22151857
TI  - Guidelines for dental radiography immediately after a dento-alveolar trauma, a
      systematic literature review.
AB  - The objective with this study was to search for and to analyze the presence of
      scientific papers, guidelines, and recommendations in dental literature regarding
      which radiographs should be prescribed after a dento-alveolar trauma. We know
      from earlier that guidelines and recommendations are available in general in
      dental traumatology. The International Association of Dental Traumatology (IADT)
      has earlier developed guidelines for the management of dental trauma cases in
      general. There are also recommendations about useful intraoral radiographic
      methods when caries and periodontal disease are studied. An additional objective
      was to provide some guidelines for general practitioners about the most accurate
      radiographic examination immediately after a dento-alveolar trauma using
      intraoral radiographs or a common extraoral imaging method. Because radiographs
      are an important diagnostic tool for establishing a correct differential
      diagnosis after a trauma, radiographic guidelines and recommendations are of
      importance to be able to start the correct treatment. PubMed Central, Cochrane
      and World Wide Web were searched and the identified existing guidelines for
      different intraoral radiographic methods in dentistry were analyzed and found to
      be very few. Those that were identified were in general not so detailed and
      specific. In conclusion, we found an explicit need for more detailed guidelines
      regarding which intraoral and other dental radiographs should be prescribed
      initially in dental traumatology.

PMID- 22151858
TI  - A review of electrical stimulation to treat motility dysfunctions in the
      digestive tract: effects and stimulation patterns.
AB  - Electrical stimulation of the digestive organs may become a valuable alternative
      to pharmaceutical and surgical approaches to the treatment of gastrointestinal
      motor dysfunctions. For more than 40 years, encouraging results with electrical
      stimulation to activate motility in gastrointestinal organs have been published.
      The most significant achievements with this work have been either stimulation to
      attenuate the symptoms of gastroparesis or stimulation to modify the feeding
      behavior in obese patients. In addition, animal studies have investigated the
      different stimulation systems and methods to activate or inhibit transit in the
      small and large intestines. This article presents a review of the published
      literature on electrical stimulation of the stomach and intestines.

PMID- 22151859
TI  - Gastrointestinal mechanisms activated by electrical stimulation to treat motility
      dysfunctions in the digestive tract: a review.
AB  - Studies performed to date have shown that electrical stimulation of the stomach
      and intestines can create or modulate motility functions in the gastrointestinal
      (GI) tract. Therefore, electrical stimulation of GI organs may become a valuable
      alternative to medication and surgical approaches in the treatment of GI motor
      dysfunctions. However, the mechanisms underlying the effects induced by
      electrical stimulation of the gut wall are not totally understood, and such
      knowledge is important for further development of stimulation methods and
      devices. Presently, it is known that electrical stimulation of GI organs triggers
      complex reactions comprising excitatory and inhibitory responses of the excitable
      components performing or controlling motility in the GI tract. I present here a
      review of what is known of the mechanisms of GI organ stimulation.

PMID- 22151860
TI  - Spinal cord stimulation with a dual quadripolar surgical lead placed in general
      anesthesia is effective in treating intractable low back and leg pain.
AB  - Objectives.  Spinal cord stimulation has been used extensively for failed back
      surgery syndrome, although dominant axial low back pain is difficult to treat
      effectively with this modality. The use of a surgically placed, double,
      quadripolar lead may result in better paresthesia of the low back, therefore
      enhancing outcomes in this difficult to treat population. Materials and Methods. 
      Accordingly, this prospective study was designed to assess the effectiveness of
      placing such a lead at the T8-T10 level under general anesthesia without
      intraoperative testing for concordancy of paresthesia distribution. Results.  The
      study showed that 70% of patients had "good" or "complete" long-term pain relief
      after placement of a surgically placed dual quadripolar lead under general
      anesthesia and analgesic consumption decreased significantly. The ability to lead
      a more active and social life was increased and 85% of patients said they would
      undergo spinal cord stimulation again. Placing the lead higher in the spinal
      canal (T8) resulted in a tendency for better paresthesia coverage of the low back
      when compared to lower lead placements. Conclusions.  Placing a double
      quadripolar paddle lead under general anesthesia resulted in good clinical
      outcome similar to other implant techniques.

PMID- 22151861
TI  - Theoretical investigation into longitudinal cathodal field steering in spinal
      cord stimulation.
AB  - Objective.  When using spinal cord stimulation (SCS) for chronic pain management,
      precise longitudinal positioning of the cathode is crucial to generate an
      electrical field capable of targeting the neural elements involved in pain
      relief. Presently used methods have a poor spatial resolution and lack
      postoperative flexibility needed for fine tuning and reprogramming the
      stimulation field after lead displacement or changes in pain pattern. We describe
      in this article a new method, "electrical field steering," to control paresthesia
      in SCS. The method takes advantage of newer stimulator design and a programming
      technique allowing for "continuous" adjustment of contact combination while
      controlling stimulation current for each contact separately. Method.  Using
      computer modeling we examined how stimulation of dorsal column (DC) and dorsal
      root (DR) fibers was influenced by changing the current ratio of the cathodes of
      a dual (--) and a guarded dual cathode (+--+) configuration programmed on a
      percutaneous lead with 9 and 4 mm center-to-center contact spacing. Results.  A
      cathodal current ratio could be found for which DC or DR fiber recruitment and
      thus, most likely, paresthesia coverage was maximized. The DR threshold profiles
      shifted longitudinally, thus following the shift in the electrical field during
      steering. The profiles had a constant shape when the contact spacing was small
      and a varying shape for wider contact separation. Generally, the wider contact
      separation provided less DC and more DR fiber recruitment. Conclusions.  By means
      of cathodal steering on a longitudinal contact array, the group of excited DC and
      DR fibers, and thus paresthesia coverage, can be controlled when using SCS. With
      widely spaced contacts, superposition of the electrical field from each steering
      contact is limited. To precisely control segmental paresthesia (DR stimulation),
      a small contact spacing is necessary.

PMID- 22151862
TI  - Challenges to setting spinal cord stimulator parameters during intraoperative
      testing: factors affecting coverage of low back and leg pain.
AB  - Objective.  Spinal cord stimulator (SCS) parameter settings have been well
      studied; however, the goal of this exploratory study was to examine the SCS
      parameters used during intra-operative stimulation (IOS) at trial lead placement.
      Methods.  In this retrospective study, we report the IOS parameter settings for
      22 patients who underwent thoracic SCS lead trial for treatment of refractory low
      back and/or leg pain. Results.  Paresthesia coverage was shown to differ
      depending upon the pain syndrome and the region involved (back and/or leg, p =
      0.03). Certain stimulation parameters were demonstrated to be linked, including
      pulse width with rate (p = 0.04) and bipolar activation distance with amplitude
      (p < 0.01). Important variations in field configuration practice patterns also
      emerged. Conclusions.  Larger prospective studies are required to confirm and
      extend the current results. The ultimate goal for this report is to establish a
      foundation for future studies to create an evidence-based standardized algorithm
      for IOS to enhance the success rate of SCS trial screening.

PMID- 22151863
TI  - Spinal Cord Stimulation for the Treatment of Upper and Lower Extremity
      Neuropathic Pain due to Lyme Disease.
AB  - Background.  Lyme disease is caused by Borrelia, a bacterium transmitted by the
      bite of a deer tick. A slow developing encephalopathy or an axonal polyneuropathy
      with distal paresthesia and spinal or radicular pain rarely occurs and can be
      hard to treat. Materials and Methods.  We report here the case of a 44-year-old
      woman with four-limb, intolerable, neuropathic pain as sequelae to Lyme disease,
      which was resistant to conservative measures and was treated successfully with
      concurrent, thoracic, and cervical percutaneous spinal cord stimulation (SCS).
      Results.  After 18 months of therapy and follow-up, this patient's analgesia, as
      a result of SCS, continues to be excellent, with almost complete subjective pain
      relief and cessation of adjuvant analgesic medication. Conclusions.  SCS may be
      efficacious for the treatment of neuropathic pain due to Lyme disease.

PMID- 22151864
TI  - Percutaneous implantation of a brachial plexus electrode for management of pain
      syndrome caused by a traction injury.
AB  - Introduction.  Intractable pain in the affected arm is a common sequel to severe
      traction lesions of the brachial plexus. Its management presents a challenge.
      Existing interventional therapies are not effective for the intractable pain from
      brachial plexus traction lesions, in the long term. Spinal cord stimulation is
      indicated for the relief of pain following peripheral nerve injury, but has its
      limitations and, in the UK, is restricted only to specialized centers. Peripheral
      neuromodulation is widely practiced noninvasively as transcutaneous electrical
      nerve stimulation and more recently, both as external neuromodulation and,
      invasively, using a surgical procedure with restricted indications. Methods.  We
      report here a single case report of the successful management of intractable pain
      of uncertain pathology following traction injury of the shoulder and brachial
      plexus with the percutaneous implantation of a permanent stimulating electrode
      via a stimulating needle to the brachial plexus using the posterior route at the
      interscalene level. Results.  Stimulation of the brachial plexus in this one
      patient has resulted in excellent pain control and unexpected beneficial sensory
      and motor changes in the arm of the patient. Conclusions.  We cautiously conclude
      that percutaneous implantation of a stimulating electrode to the brachial plexus
      via a stimulating needle is a relatively simple procedure when compared to
      surgical implantation and, as shown in our case, very effective.

PMID- 22151865
TI  - The effect of spinal cord stimulation, overall, and the effect of differing
      spinal cord stimulation technologies on pain, reduction in pain medication,
      sleep, and function.
AB  - Background.  Spinal cord stimulation (SCS) is effective in reducing pain from a
      number of differing medical conditions that are refractory to other, more
      conservative treatments. Much is written in the literature regarding efficacy and
      safety of SCS; however, no one to our knowledge has compared and reported safety
      and efficacy of SCS when using differing manufactured SCS devices. We undertook
      such a preliminary evaluation. Methods.  Charts from the years 2001-2005 of our
      clinic's patients who had undergone trials and placement of permanent SCS systems
      were selected for review. All patients who had received either an Advanced
      Bionics SCS system (Advanced Bionics, Valencia, CA, USA), an Advanced
      Neuromodulation Systems (ANS) SCS system (ANS, Plano, TX, USA), or a Medtronic
      SCS system (Medtronic, Inc., Minneapolis, MN, USA) were given a survey to
      complete for data analysis. Patients were categorized into three groups: those
      patients having received a Medtronic (Mdt) SCS system, those patients having
      received an Advance Bionics (ABi) SCS system, and those patients having received
      an Advance Neuromodulation Systems (ANS) SCS system. Data, limited to volunteers,
      who gave their written consent, were analyzed for efficacy and complications.
      Differences in outcomes and safety were analyzed overall and according to
      manufacturer. Results.  Eighty surveys were mailed out to 80 patients and 30
      surveys were completed and returned, a return and completion rate of 37.5%. All
      patients showed improvement in all aspects including pain relief, sleep,
      functional activities, and medication use for pain control. When comparing
      outcomes of SCS from the three different companies, there was no significant
      statistical difference in average percentage pain relief, sleep improvement, and
      medication needed for pain control. However, there was a statistically different
      less change in functional improvement in the ABi group when compared to patients
      in the Mdt and ANS groups. Conclusions.  Spinal cord stimulation improves pain,
      sleep, and function in patients with intractable pain. Because of the low number
      of patients evaluable in this study, we believe that conclusions should not be
      made regarding the effect of technology on outcomes or safety. We believe that an
      analysis of this type in larger populations is warranted to understand the role,
      if any, that present-day technology has on outcomes of SCS.

PMID- 22151866
TI  - Technique that better localizes the dura mater during intrathecal catheterization
      should reduce inadvertent multiple dural punctures and reduce complications.
AB  - We present here a technique to mitigate the complication of multiple needle
      entries into the thecal sac when attempting to place an intrathecal catheter into
      the thecal sac. Our technique of injecting radio-opaque contrast material after
      entering the epidural space and before entering the thecal sac allows for
      visualization of the thecal sac within the spinal canal, thus obviating the
      technique of "fell and pop" to enter the sac. In our hands, this technique has
      improved outcomes for our patients and has decreased the incidence of post dural
      puncture headache, neural trauma and technical failures.

PMID- 22151867
TI  - The management of pain from collapse of osteoporotic vertebrae with continuous
      intrathecal morphine infusion.
AB  - Objectives.  Vertebral fractures are the most common consequences of severe
      osteoporosis. The chronic pain from collapse of osteoporotic vertebrae affects
      quality of life (QoL) and autonomy of patients. The management of pain with oral
      or transdermal opiates can cause severe side-effects. Continuous intrathecal
      administration of morphine through an implantable pump might represent an
      alternative therapy to conventional oral or transdermal administration of opioids
      and has some advantages and disadvantages for pain relief and improvement in QoL
      when compared to conventional opioid delivery. It is our objective to report our
      experience using intrathecal delivery of analgesics in a population of patients
      with refractory pain due to vertebral fractures. Materials and Methods.  In 24
      patients, refractory to conventional delivery of opioids, we used intrathecal
      analgesic therapy. To test for efficacy and improvement in QoL, we administered
      the visual analog scale (VAS) for pain and the Quality of Life Questionnaire of
      the European Foundation for Osteoporosis (QUALEFFO). Before patients were
      selected for pump implantation, an intraspinal drug delivery trial was performed
      to monitor side-effects and responses to intrathecal therapy. Results. 
      Significant pain relief was obtained in all implanted patients. Using the
      QUALEFFO, we observed significant improvement of all variables such as QDL
      (quality of daily life), DW (domestic work), ambulation, and PHS (perception of
      health status), before and after one year after pump implantation. With
      intrathecal morphine infusion, none of the 24 patients required additional
      systemic analgesic medication. The mean morphine dose during the spinal trial was
      11.28 mg/day, 7.92 mg/day at pump implantation, and 16.32 mg/day at one-year
      follow-up. Conclusions.  Our results show that intrathecal administration of
      morphine efficiently relieves the symptoms of pain and improves QoL. Continuous
      intrathecal administration of morphine appears to be an alternative therapy to
      conventional analgesic drug delivery and has advantages in those patients who
      have severe side-effects with systemic administration of analgesics.

PMID- 22151868
TI  - Ethical and legal aspects of neuromodulation: on the road to guidelines: fourth
      meeting of the benelux neuromodulation society, chapter of the international
      neuromodulation society november 17-18, 2006, maastricht, the Netherlands.

PMID- 22151869
TI  - Abstracts From the 10th Annual Meeting of the North American Neuromodulation
      Society: December 7-10, 2006, Las Vegas, NV, USA.

PMID- 22151870
TI  - Proceedings from the 6th meeting of the neuromodulation society of the United
      kingdom and ireland: october 19-21, 2006, cork, ireland.

PMID- 22151871
TI  - Low bone mineral density is associated with poor clinical outcome in acute
      ischemic stroke.
AB  - BACKGROUND: Chronic low bone mineral density is associated with an increased risk
      of stroke. However, little is known about the influence of bone mineral density
      at the time of stroke on clinical outcome. We investigated the association
      between bone mineral density and functional disability at three-months in
      patients with acute ischemic stroke. METHODS: We retrospectively examined
      consecutive acute ischemic stroke patients who underwent bone densitometry tests
      within seven-days of stroke symptom onset. Patient demographics, risk factors,
      and initial National Institute of Health Stroke Scale scores were assessed. Bone
      mineral density was measured at the lumbar spine and bilateral femoral necks.
      Osteoporosis was defined as bone mineral density <=-2.5 T-scores at each site.
      The primary outcome was modified Rankin Scale at 90 days poststroke. A favorable
      outcome was defined as modified Rankin Scale 0-1 and poor outcome as modified
      Rankin Scale 2-6. RESULTS: Of the 191 patients included, 61 (31.9%) were men.
      Mean age (+/-standard deviation) was 69.8 +/- 11.1 years. Patients with
      osteoporosis of the right femoral neck were more likely to have poor outcome
      (25/82; 30.5%) than those without (12/109; 11.0%, P = 0.001). After adjustment
      for age, sex, and initial National Institute of Health Stroke Scale score,
      osteoporosis of the right femoral neck was significantly associated with poor
      outcome (odds ratio, 2.97; 95% confidence interval 1.21 to 7.32, P = 0.018).
      CONCLUSIONS: Low bone mineral density of the right femur in the acute poststroke
      period is associated with poor outcome at three-months. Assessment of bone
      mineral density in acute stroke patients may be a useful prognosticator and
      facilitate early intervention.

PMID- 22151872
TI  - Detection of interaction articles and experimental methods in biomedical
      literature.
AB  - BACKGROUND: This article describes the approaches taken by the OntoGene group at
      the University of Zurich in dealing with two tasks of the BioCreative III
      competition: classification of articles which contain curatable protein-protein
      interactions (PPI-ACT) and extraction of experimental methods (PPI-IMT). RESULTS:
      Two main achievements are described in this paper: (a) a system for document
      classification which crucially relies on the results of an advanced pipeline of
      natural language processing tools; (b) a system which is capable of detecting all
      experimental methods mentioned in scientific literature, and listing them with a
      competitive ranking (AUC iP/R > 0.5). CONCLUSIONS: The results of the BioCreative
      III shared evaluation clearly demonstrate that significant progress has been
      achieved in the domain of biomedical text mining in the past few years. Our own
      contribution, together with the results of other participants, provides evidence
      that natural language processing techniques have become by now an integral part
      of advanced text mining approaches.

PMID- 22151873
TI  - Development of a romifidine constant rate infusion with or without butorphanol
      for standing sedation of horses.
AB  - OBJECTIVE: To determine constant rate infusion (CRI) protocols for romifidine (R)
      and romifidine combined with butorphanol (RB) resulting in constant sedation and
      romifidine plasma concentrations. STUDY DESIGN: Blinded randomized crossover
      study. ANIMALS: Ten adult research horses. METHODS: Part I: After determining
      normal height of head above ground (HHAG = 100%), loading doses of romifidine (80
      MUg kg(-1)) with butorphanol (RB: 18 MUg kg(-1)) or saline (R) were given
      intravenously (IV). Immediately afterwards, a butorphanol (RB: 25 MUg kg(-1)
      hour(-1)) or saline (R) CRI was administered for 2 hours. The HHAG was used as
      marker of sedation depth. Sedation was maintained for 2 hours by additional
      romifidine (20 MUg kg(-1) ) whenever HHAG > 50%. The dose rate of romifidine (MUg
      kg(-1) hour(-1)) required to maintain sedation was calculated for both
      treatments. Part II: After loading doses, the romifidine CRIs derived from part I
      were administered in parallel to butorphanol (RB) or saline (R). Sedation and
      ataxia were evaluated periodically. Romifidine plasma concentrations were
      measured by HPLC-MS-MS at 0, 5, 10, 15, 30, 45, 60, 90, 105, and 120 minutes.
      Data were analyzed using paired t-test, Fisher's exact test, Wilcoxon signed rank
      test, and two-way anova for repeated measures (p < 0.05). RESULTS: There was no
      significant difference in romifidine requirements (R: 30; RB: 29 MUg kg(-1) hour(
      1)). CRI protocols leading to constant sedation were developed. Time to first
      additional romifidine bolus was significantly longer in RB (mean +/- SD, R: 38.5
      +/- 13.6; RB: 50.5 +/- 11.7 minutes). Constant plasma concentrations of
      romifidine were achieved during the second hour of CRI. Ataxia was greater when
      butorphanol was added. CONCLUSION: Romifidine bolus, followed by CRI, provided
      constant sedation assessed by HHAG. Butorphanol was ineffective in reducing
      romifidine requirements in unstimulated horses, but prolonged the sedation caused
      by the initial romifidine bolus. CLINICAL RELEVANCE: Both protocols need to be
      tested under clinical conditions.

PMID- 22151874
TI  - Correlation between clinical signs of depth of anaesthesia and cerebral state
      index responses in dogs with different target-controlled infusions of propofol.
AB  - OBJECTIVE: To evaluate if the cerebral state index (CSI), measured by a Cerebral
      State Monitor (CSM), can predict depth of anaesthesia as assessed clinically or
      by estimated propofol plasma concentrations. STUDY DESIGN: Prospective clinical
      study. ANIMALS: Fourteen mixed breed dogs, weighing 24.5 +/- 4.7 kg, scheduled to
      undergo neutering procedures. METHODS: Dogs were premedicated with 0.05 mg kg(-1)
      acepromazine intramuscularly. The CSM and cardiovascular monitoring equipment
      were attached. Anaesthesia was induced with propofol using a target controlled
      infusion (TCI) to varying plasma propofol targets (PropCp). Following
      endotracheal intubation the dogs were ventilated with oxygen. Anaesthetic
      maintenance was with propofol by TCI. A PropCp of 3 MUg dL(-1) was set initially,
      then PropCps were increased in 1 MUg dL(-1) steps to 7, 9 and then 11 MUg dL(-1).
      Each PropCp was held constant for a 5 minute period, at the end of which depth of
      anaesthesia was classified using a previously evaluated scale of 'planes' based
      on palpebral and corneal reflexes and eye position. Cerebral state index (CSI),
      burst suppression (BSR) and electromyogram were measured at these time points.
      The prediction probability (PK) of these variables, or of the PropCp in
      predicting depth of anaesthesia was calculated. RESULTS: The PKs for predicting
      anaesthetic planes were 0.74, 0.91, 0.76 and 0.78 for CSI, BSR, EMG and PropCp,
      respectively. The PKs for PropCp to predict CSI, BSR and EMG were 0.65, 0.71 and
      0.65 respectively. CONCLUSION AND CLINICAL RELEVANCE: The Cerebral State Monitor
      was able to detect very deep planes of anaesthesia when BSR occurs, but was not
      able to distinguish between the intermediate anaesthetic planes likely to be used
      in clinical anaesthesia.

PMID- 22151875
TI  - Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary
      function and recovery quality in isoflurane anaesthetized horses.
AB  - OBJECTIVE: To investigate the influence of a dexmedetomidine constant rate
      infusion (CRI) in horses anaesthetized with isoflurane. STUDY DESIGN:
      Prospective, randomized, blinded, clinical study. ANIMALS: Forty adult healthy
      horses (weight mean 491 +/- SD 102 kg) undergoing elective surgery. METHODS:
      After sedation [dexmedetomidine, 3.5 MUg kg(-1) intravenously (IV)] and induction
      IV (midazolam 0.06 mg kg(-1), ketamine 2.2 mg kg(-1)), anaesthesia was maintained
      with isoflurane in oxygen/air (FiO(2) 55-60%). Horses were ventilated and
      dobutamine was administered when hypoventilation [arterial partial pressure of
      CO(2) > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred
      respectively. During anaesthesia, horses were randomly allocated to receive a CRI
      of dexmedetomidine (1.75 MUg kg(-1) hour(-1) ) (D) or saline (S). Monitoring
      included end-tidal isoflurane concentration, cardiopulmonary parameters, and need
      for dobutamine and additional ketamine. All horses received 0.875 MUg kg(-1)
      dexmedetomidine IV for the recovery period. Age and weight of the horses,
      duration of anaesthesia, additional ketamine and dobutamine, cardiopulmonary data
      (anova), recovery scores (Wilcoxon Rank Sum Test), duration of recovery (t-test)
      and attempts to stand (Mann-Whitney test) were compared between groups.
      Significance was set at p < 0.05. RESULTS: Heart rate and arterial partial
      pressure of oxygen were significantly lower in group D compared to group S. An
      interaction between treatment and time was present for cardiac index, oxygen
      delivery index and systemic vascular resistance. End-tidal isoflurane
      concentration and heart rate significantly increased over time. Packed cell
      volume, systolic, diastolic and mean arterial pressure, arterial oxygen content,
      stroke volume index and systemic vascular resistance significantly decreased over
      time. Recovery scores were significantly better in group D, with fewer attempts
      to stand and significantly longer times to sternal position and first attempt to
      stand. CONCLUSIONS AND CLINICAL RELEVANCE: A dexmedetomidine CRI produced limited
      cardiopulmonary effects, but significantly improved recovery quality.

PMID- 22151876
TI  - Risk of anaesthetic mortality in dogs and cats: an observational cohort study of
      3546 cases.
AB  - OBJECTIVE: To evaluate the anaesthetic death risk for dogs and cats in a French
      private practice. STUDY DESIGN: Observational cohort study. ANIMAL POPULATION:
      All small animals anesthetized at the Centre Hospitalier Veterinaire des
      Cordeliers between April 15th, 2008 and April 15th, 2010. METHODS: General
      anaesthesia was defined as a drug-induced unconsciousness characterised by a
      controlled and reversible depression of the central nervous system and analgesia,
      sufficient to allow endotracheal intubation. Patient outcome (alive or dead) was
      assessed at the end of anaesthesia defined as the meeting point of the return of
      consciousness, rectal temperature >36  degrees C and ability to maintain sternal
      recumbency. Death occurring during anaesthesia was recorded. Relationship between
      anaesthetic death and ASA status, species, age, nature of the procedure,
      anaesthetic protocol and occurrence of epidural administration of a combination
      of morphine and bupivacaine were analysed. RESULTS: During the study period 3546
      animals underwent general anaesthesia. The overall death rate in the present
      study was 1.35% (48 in 3546, 95% CI 0.96-1.75). The death rate of healthy animals
      (ASA 1 and 2) was 0.12% (3 in 2602 95% CI 0.02-0.34). For sick animals (ASA
      status 3 and over), the overall death rate was 4.77% (45 in 944 95% CI 3.36
      6.18). The death rates in the ASA 3, 4 and 5 categories were 2.90%, 7.58% and
      17.33%, respectively. The main factor associated with increased odds of
      anaesthetic death in ASA categories 3 and over was poor health status (ASA
      physical status classification). The nature of the procedure the patient
      underwent and epidural administration of a combination of morphine and
      bupivacaine were not correlated with the occurrence of death during anaesthesia.
      Neither species nor age effects were detected. CONCLUSION AND CLINICAL RELEVANCE:
      Specific factors were associated with increased odds of anaesthetic death,
      especially poor health status. Efforts must be directed towards thorough
      preoperative patient evaluation and improvement of clinical conditions if
      possible. Identification of risk factors before anaesthesia should lead to
      increased surveillance by trained staff. This could result in better outcomes.

PMID- 22151877
TI  - Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs.
AB  - OBJECTIVES: To discuss the clinical pharmacology of currently licensed veterinary
      NSAIDs and to review gastrointestinal and renal adverse effects as well as drug
      drug interactions that have been reported with these drugs. To review the use of
      NSAIDs in the peri-operative setting and their use in patients with
      osteoarthritis. To further review the reported effects of NSAIDs on canine
      articular cartilage and liver as well as the clinical relevance of a washout
      period. DATABASES USED: PubMed, CAB abstracts and Google Scholar using dog, dogs,
      nonsteroidal anti-inflammatory drugs and NSAID(s) as keywords. CONCLUSIONS: A
      good understanding of the mechanisms by which NSAIDs elicit their analgesic
      effect is essential in order to minimize adverse effects and drug-drug
      interactions. Cyclooxygenase (COX) is present in at least two active isoforms in
      the body and is the primary pharmacologic target of NSAIDs. Inhibition of COX is
      associated with the analgesic effects of NSAIDs. COX is present in the
      gastrointestinal tract and kidneys, along with other areas of the body, and is
      also the likely reason for many adverse effects including gastrointestinal and
      renal adverse effects. The newer veterinary approved NSAIDs have a lower
      frequency of gastrointestinal adverse effects in dogs compared to drugs such as
      aspirin, ketoprofen and flunixin, which may be due to differential effects on the
      COX isoforms. There are currently no published reports demonstrating that the
      newer NSAIDs are associated with fewer renal or hepatic adverse effects in dogs.
      NSAIDs remain the cornerstone of oral therapy for osteoarthritis unless
      contraindicated by intolerance, concurrent therapies or underlying medical
      conditions. NSAIDs are also effective and frequently used for the management of
      post-operative pain.

PMID- 22151879
TI  - An invasive adenocarcinoma of the accessory parotid gland: a rare example
      developing from a low-grade cribriform cystadenocarcinoma?
AB  - Low-grade cribriform cystadenocarcinoma (LGCCA) is a rare tumor of the salivary
      gland that exhibits clinically indolent behavior. In this paper, we present a
      case of invasive adenocarcinoma of the accessory parotid gland in a young male
      that exhibited histology suggestive of an association of LGCCA. A 27-year-old man
      presented with a subcutaneous tumor in his left cheek. The tumor was separated
      from the parotid gland and located on the masseter muscle. The tumor was
      resected, and the postoperative histological diagnosis was adenocarcinoma, not
      otherwise specified (ANOS). The tumor exhibited papillary-cystic and cribriform
      proliferation of the duct epithelium and obvious stromal infiltration. Some tumor
      nests were rimmed by myoepithelium positive for smooth muscle actin, p63, and
      cytokeratin 14, indicating the presence of intraductal components of the tumor.
      Tumor cells exhibited mild nuclear atypia, and some of them presented an apocrine
      like appearance and had cytoplasmic PAS-positive/diastase-resistant granules and
      hemosiderin. Other cells had foamy cytoplasm with microvacuoles.
      Immunohistochemistry revealed that the almost all of the tumor cells were
      strongly positive for S-100. These histological findings suggest the possibility
      that ANOS might arise secondarily from LGCCA. This is an interesting case
      regarding the association between ANOS and LGCCA in oncogenesis. VIRTUAL SLIDES:
      The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1226764594634693.

PMID- 22151881
TI  - A comparative study between fluoroscopic and endoscopic guidance in palliative
      esophageal stent placement.
AB  - Self-expanding metallic stents (SEMS) are the treatment of choice for incurable
      obstructive malignant esophageal strictures. Although the placement of SEMS is
      usually performed with fluoroscopic control (FC), recently several authors have
      shown the feasibility of placing SEMS under endoscopic control alone (EC).
      However, studies comparing the two techniques are lacking. The objective of this
      study was to compare the feasibility and safety of SEMS insertion under
      fluoroscopic control and endoscopic control. The study was performed through the
      retrospective analysis of patients who underwent SEMS insertion for malignant
      dysphagia between January 2005 and January 2010. Data concerning early and late
      complications and survival were retrieved. Early complications were defined as
      pain, vomiting, bleeding, malposition/migration, perforation, and/or dysphagia
      occurring until 30 days of SEMS insertion; and late complications as tumor
      ingrowth and overgrowth, migration, hemorrhage, fistulae, food impaction, and/or
      esophagitis occurring after 30 days. We placed 126 SEMS of which 87% for
      esophageal stricture, 8% for esophagus-respiratory fistula, and 5% for extrinsic
      compression. The mean age of the patients was 62 years, and 93 were male. SEMS
      insertion was performed with FC in 66 patients and EC in 60. Early complications
      occurred in 34 patients (52%) in the FC group and 28 (47%) in the EC group
      (P=0.71), including: pain in 22 patients of the FC group and 15 of the EC group
      (P=0.31); vomiting in 15 of the FC group and nine of the EC group (P=0.27);
      malposition/migration in three of the FC group and four of the EC group (P=0.60);
      hemorrhage in one of the FC group and two of the EC group (P=0.27); and dysphagia
      in two of the FC group and three of the EC group (P=0.57). Late complications
      occurred in 20 patients (30%) in the FC group and 22 (37%) in the EC group
      (P=0.44), including: tumor in/overgrowth in 13 patients of the FC group and 10 of
      the EC group (P=0.66); prostheses migration in five of the FC group and eight of
      the EC group (P=0.28); hemorrhage in two of the FC group and two of the EC group
      (P=0.54); appearance of esophageal fistulae in seven of the FC group and four of
      the EC group (P=0.43); food impaction in nine of the FC group and eight of the EC
      group (P=0.96); esophagitis in 12 of the FC group and 15 of the EC group
      (P=0.35). Median survival was 107 days (95% confidence interval [CI]=6-369 days)
      with no difference between the two groups. There were no statistical significant
      differences in the incidence of complications and in survival between patients
      undergoing SEMS placement under fluoroscopic control or endoscopic control.

PMID- 22151880
TI  - Increase in the incidence of type 1 diabetes in Israeli children following the
      Second Lebanon War.
AB  - BACKGROUND: Type 1 diabetes is an autoimmune disease occurring in genetically
      susceptible individuals. The precipitating cause is unclear. Recently, the Second
      Lebanon War exposed a large civilian population in northern Israel to significant
      psychological stress in the form of repeated barrages of missile attacks.
      HYPOTHESIS: We hypothesized that trends in regional incidence of type 1 diabetes
      before and after the war would reflect an association with stress. METHODS: All
      type 1 diabetes patients aged 0-17 yr who were reported to the Israel Juvenile
      Diabetes Register (n = 1822) in the four pre-war (2002-2005) and two post-war
      years (2006-2007) were included in the study. The patients were stratified by
      gender, age, ethnicity, family history of type 1 diabetes, season at diagnosis,
      and region of residency, namely, those who lived in the northern regions that
      were attacked and those in other regions. RESULTS: The post-war incidence of type
      1 diabetes was increased in the northern regions (rate ratio, RR = 1.27; p =
      0.037), with no change in the other regions. This change was more prominent in
      males (RR = 1.55; p = 0.005) but similar in summer and winter, in different ages,
      and in different ethnic groups. There was no change in the proportion of new
      patients with a family history of the disease. CONCLUSIONS: For the first time in
      a large population, we found a positive association between the trauma of war and
      an increase in the incidence of type 1 diabetes in children and adolescents. The
      increase in incidence was not associated with genetic susceptibility to the
      disease.

PMID- 22151882
TI  - STELLAR: fast and exact local alignments.
AB  - BACKGROUND: Large-scale comparison of genomic sequences requires reliable tools
      for the search of local alignments. Practical local aligners are in general fast,
      but heuristic, and hence sometimes miss significant matches. RESULTS: We present
      here the local pairwise aligner STELLAR that has full sensitivity for epsilon
      alignments, i.e. guarantees to report all local alignments of a given minimal
      length and maximal error rate. The aligner is composed of two steps, filtering
      and verification. We apply the SWIFT algorithm for lossless filtering, and have
      developed a new verification strategy that we prove to be exact. Our results on
      simulated and real genomic data confirm and quantify the conjecture that
      heuristic tools like BLAST or BLAT miss a large percentage of significant local
      alignments. CONCLUSIONS: STELLAR is very practical and fast on very long
      sequences which makes it a suitable new tool for finding local alignments between
      genomic sequences under the edit distance model. Binaries are freely available
      for Linux, Windows, and Mac OS X at http://www.seqan.de/projects/stellar. The
      source code is freely distributed with the SeqAn C++ library version 1.3 and
      later at http://www.seqan.de.

PMID- 22151883
TI  - Gold nanoparticles administration induces disarray of heart muscle, hemorrhagic,
      chronic inflammatory cells infiltrated by small lymphocytes, cytoplasmic
      vacuolization and congested and dilated blood vessels.
AB  - BACKGROUND: Despite significant research efforts on cancer therapy, diagnostics
      and imaging, many challenges remain unsolved. There are many unknown details
      regarding the interaction of nanoparticles (NPs) and biological systems. The
      structure and properties of gold nanoparticles (GNPs) make them useful for a wide
      array of biological applications. However, for the application of GNPs in therapy
      and drug delivery, knowledge regarding their bioaccumulation and associated local
      or systemic toxicity is necessary. Information on the biological fate of NPs,
      including distribution, accumulation, metabolism, and organ specific toxicity is
      still minimal. Studies specifically dealing with the toxicity of NPs are rare.
      The aim of the present study was to investigate the effects of intraperitoneal
      administration of GNPs on histological alterations of the heart tissue of rats in
      an attempt to identify and understand the toxicity and the potential role of GNPs
      as a therapeutic and diagnostic tool. METHODS: A total of 40 healthy male Wistar
      Kyoto rats received 50 MUl infusions of 10, 20 and 50 nm GNPs for 3 or 7 days.
      Animals were randomly divided into groups: 6 GNP-treated rats groups and one
      control group (NG). Groups 1, 2 and 3 received infusions of 50 MUl GNPs of size
      10 nm (3 or 7 days), 20 nm (3 or 7 days) and 50 nm (3 or 7 days), respectively.
      RESULTS: In comparison with the respective control rats, exposure to GNPs doses
      produced heart muscle disarray with a few scattered chronic inflammatory cells
      infiltrated by small lymphocytes, foci of hemorrhage with extravasation of red
      blood cells, some scattered cytoplasmic vacuolization and congested and dilated
      blood vessels. None of the above alterations were observed in the heart muscle of
      any member of the control group. CONCLUSIONS: The alterations induced by
      intraperitoneal administration of GNPs were size-dependent, with smaller ones
      inducing greater affects, and were also related to the time exposure to GNPs.
      These alterations may indicate scattered cytoplasmic vacuolization, which may
      induce the toxicity effect through an inability to deal with the accumulated
      residues resulting from metabolic and structural disturbances caused by these
      NPs. These histological alterations were more prominent with 10 nm size particles
      than with the larger ones. The interaction of GNPs with proteins and various cell
      types should be considered as part of the toxicological evaluation. Additional
      experiments related to plasma, tissues cytokine, antioxidant defense mechanism,
      lipid peroxidation, histomorphologcal and ultrastructure will be performed to
      identify and understand the toxicity and the potential use of GNPs as therapeutic
      and diagnostic tools.

PMID- 22151884
TI  - The so-called "Spanish model" - tobacco industry strategies and its impact in
      Europe and Latin America.
AB  - BACKGROUND: To demonstrate the tobacco industry rationale behind the "Spanish
      model" on non-smokers' protection in hospitality venues and the impact it had on
      some European and Latin American countries between 2006 and 2011. METHODS:
      Tobacco industry documents research triangulated against news and media reports.
      RESULTS: As an alternative to the successful implementation of 100% smoke-free
      policies, several European and Latin American countries introduced partial
      smoking bans based on the so-called "Spanish model", a legal framework widely
      advocated by parts of the hospitality industry with striking similarities to
      "accommodation programmes" promoted by the tobacco industry in the late 1990s.
      These developments started with the implementation of the Spanish tobacco control
      law (Ley 28/2005) in 2006 and have increased since then. CONCLUSION: The Spanish
      experience demonstrates that partial smoking bans often resemble tobacco industry
      strategies and are used to spread a failed approach on international level.
      Researchers, advocates and policy makers should be aware of this ineffective
      policy.

PMID- 22151885
TI  - Phospholipase C mediates cadmium-dependent apoptosis in HEK 293 cells.
AB  - Cadmium is a heavy metal that is known to cause toxicity to cells and, at low
      concentrations, can initiate apoptosis. This study was undertaken with the aim of
      defining the role of phospholipase C (PLC) in mediating cadmium-induced apoptosis
      in human embryonic kidney (HEK 293) cells. We have shown that intracellular
      Ca(2+)  levels increased significantly in HEK 293 cells after 24-hr exposure to
      Cd. The activity of the calcium-dependent protease calpain rose by four times.
      The PLC-specific inhibitor, U73122, prevented the Cd-dependent increase in Ca(2+)
      levels and also abolished Cd-dependent calpain and caspase 3 activation as well
      as Cd-dependent mitochondrial Bax accumulation. Inhibition of PLC also leads to
      an increased cell viability following exposure to Cd. Taken together, the results
      show that the PLC pathway is involved in mediating Cd-induced apoptosis in HEK
      293 cells.

PMID- 22151887
TI  - Cryopreservation of human failed-matured oocytes followed by in vitro maturation:
      vitrification is superior to the slow freezing method.
AB  - BACKGROUND: Oocyte cryopreservation is an important method used in a number of
      human fertility circumstances. Here, we compared the survival, in vitro
      maturation, fertilization, and early embryonic development rates of frozen-thawed
      human immature oocytes using two different cryopreservation methods. METHODS: A
      total of 454 failed-matured oocytes [germinal vesicle (GV) and metaphase I (MI)
      stages] were collected from 135 patients (mean age 33.84 +/- 5.0 y) who underwent
      intracytoplasmic sperm injection (ICSI) cycles between February 2009 and December
      2009 and randomly divided into a slow freezing group [1.5 mol/L-1, 2-propanediol
      (PROH) + 0.2 mol/l sucrose] and vitrification group [20% PROH + 20% ethylene
      glycol (EG) + 0.5 mol/l sucrose]. RESULTS: The vitrification protocol yielded a
      better survival rate than the slow freezing protocol at each maturation stage
      assessed. Regardless of the maturation stage (GV + MI), the slow freezing
      protocol had a significantly lower survival rate than the vitrification protocol
      (p < 0.001). In addition, a significant difference was found in the survival
      rates between GV and MI oocytes regardless of the protocol used (90.1 vs. 64.7%,
      respectively; p < 0.01). We also found that the maturation rates of GV and MI
      oocytes from the slow freezing and vitrification groups were 16.7 vs. 24.4% and
      50.8 vs. 55.4%, respectively. Regardless of the protocol used, the GV oocytes had
      significantly lower viability than MI oocytes after 36 h of in vitro maturation
      (21.2 vs. 54.0%, respectively; p < 0.01). In addition, the GV and MI oocytes from
      the slow freezing group had a markedly lower maturation rate than those from the
      vitrification group (33.6 vs. 43.1%, respectively), but no statistical difference
      was found between the two groups (P > 0.05). For the GV-matured oocytes, no
      fertilized eggs were obtained in the slow-freezing group, while a 19.0% (4/21)
      fertilization rate was observed in the vitrification group. For the MI-matured
      oocytes, fertilization rates for the slow freezing and vitrified groups were 36%
      and 61.1%, respectively, but no significant difference was found between the two
      groups (PIn the Methods section in the MS, all procedures were compliant with
      ethical guidelines, i.e. approved by the Ethical Committee of our university and
      Informed Consent signed by each patient. > 0.05). In the GV vitrification group,
      no embryo formed; however, in the MI slow freezing group, 12 oocytes were
      fertilized, but only two achieved cleavage and were subsequently blocked at the 2
      cell stage. In the MI vitrification group, a total of 22 embryos were obtained,
      five of which developed to the blastocyst stage. CONCLUSIONS: Vitrification is
      superior to the slow freezing method in terms of the survival and developmental
      rates for the cryopreservation of human failed-matured oocytes. In addition, GV
      oocytes appeared to be more resistant than MI oocytes to the low temperature and
      cryoprotectant used during cryopreservation.

PMID- 22151888
TI  - Determinants of low family planning use and high unmet need in Butajira District,
      South Central Ethiopia.
AB  - BACKGROUND: The rapid population growth does not match with available resource in
      Ethiopia. Though household level family planning delivery has been put in place,
      the impact of such programs in densely populated rural areas was not studied. The
      study aims at measuring contraception and unmet need and identifying its
      determinants among married women. METHODS: A total of 5746 married women are
      interviewed from October to December 2009 in the Butajira Demographic
      Surveillance Area. Contraceptive prevalence rate and unmet need with their 95%
      confidence interval is measured among married women in the Butajira district. The
      association of background characteristics and family planning use is ascertained
      using crude and adjusted Odds ratio in logistic regression model. RESULTS:
      Current contraceptive prevalence rate among married women is 25.4% (95% CI: 24.2,
      26.5). Unmet need of contraception is 52.4% of which 74.8% was attributed to
      spacing and the rest for limiting. Reasons for the high unmet need include
      commodities' insecurity, religion, and complaints related to providers, methods,
      diet and work load. Contraception is 2.3 (95% CI: 1.7, 3.2) times higher in
      urbanites compared to rural highlanders. Married women who attained primary and
      secondary plus level of education have about 1.3 (95% CI: 1.1, 1.6) and 2 (95%
      CI: 1.4, 2.9) times more risk to contraception; those with no child death are 1.3
      (95% CI: 1.1, 1.5) times more likely to use contraceptives compared to
      counterparts. Besides, the odds of contraception is 1.3 (95% CI: 1.1, 1.6) and
      1.5 (1.1, 2.0) times more likely among women whose partners completed primary and
      secondary plus level of education. Women discussing about contraception with
      partners were 2.2 (95% CI: 1.8, 2.7) times more likely to use family planning.
      Nevertheless, contraception was about 2.6 (95% CI: 2.1, 3.2) more likely among
      married women whose partners supported the use of family planning. CONCLUSIONS:
      The local government should focus on increasing educational level. It must also
      ensure family planning methods security, increase competence of providers, and
      create awareness on various methods and their side effects to empower women to
      make an appropriate choice. Emphasis should be given to rural communities.

PMID- 22151886
TI  - Effects of human immunodeficiency virus and metabolic complications on myocardial
      nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional
      analysis.
AB  - BACKGROUND: In the general population, peripheral metabolic complications (MC)
      increase the risk for left ventricular dysfunction. Human immunodeficiency virus
      infection (HIV) and combination anti-retroviral therapy (cART) are associated
      with MC, left ventricular dysfunction, and a higher incidence of cardiovascular
      events than the general population. We examined whether myocardial nutrient
      metabolism and left ventricular dysfunction are related to one another and worse
      in HIV infected men treated with cART vs. HIV-negative men with or without MC.
      METHODS: Prospective, cross-sectional study of myocardial glucose and fatty acid
      metabolism and left ventricular function in HIV+ and HIV-negative men with and
      without MC. Myocardial glucose utilization (GLUT), and fatty acid oxidation and
      utilization rates were quantified using 11C-glucose and 11C-palmitate and
      myocardial positron emission tomography (PET) imaging in four groups of men: 23
      HIV+ men with MC+ (HIV+/MC+, 42 +/- 6 yrs), 15 HIV+ men without MC (HIV+/MC-, 41
      +/- 6 yrs), 9 HIV-negative men with MC (HIV-/MC+, 33 +/- 5 yrs), and 22 HIV
      negative men without MC (HIV-/MC-, 25 +/- 6 yrs). Left ventricular function
      parameters were quantified using echocardiography. RESULTS: Myocardial glucose
      utilization was similar among groups, however when normalized to fasting plasma
      insulin concentration (GLUT/INS) was lower (p < 0.01) in men with metabolic
      complications (HIV+: 9.2 +/- 6.2 vs. HIV-: 10.4 +/- 8.1 nmol/g/min/MUU/mL) than
      men without metabolic complications (HIV+: 45.0 +/- 33.3 vs. HIV-: 60.3 +/- 53.0
      nmol/g/min/MUU/mL). Lower GLUT/INS was associated with lower myocardial
      relaxation velocity during early diastole (r = 0.39, p < 0.001). CONCLUSION: Men
      with metabolic complications, irrespective of HIV infection, had lower basal
      myocardial glucose utilization rates per unit insulin that were related to left
      ventricular diastolic impairments, indicating that well-controlled HIV infection
      is not an independent risk factor for blunted myocardial glucose utilization per
      unit of insulin. TRIAL REGISTRATION: NIH Clinical Trials NCT00656851.

PMID- 22151889
TI  - The immunosuppressant FTY720 (fingolimod) enhances glycosaminoglycan depletion in
      articular cartilage.
AB  - BACKGROUND: FTY720 (Fingolimod) is a novel immunosuppressive drug investigated in
      clinical trials for organ transplantation and multiple sclerosis. It acts as a
      functional sphingosine-1-phosphate (S1P) receptor antagonist, thereby inhibiting
      the egress of lymphocytes from secondary lymphoid organs. As S1P is able to
      prevent IL-1beta induced cartilage degradation, we examined the direct impact of
      FTY720 on cytokine induced cartilage destruction. METHODS: Bovine chondrocytes
      were treated with the bioactive phosphorylated form of FTY720 (FTY720-P) in
      combination with IL-1beta or TNF-alpha. Expression of MMP-1,-3.-13, iNOS and
      ADAMTS-4,-5 and COX-2 was evaluated using quantitative real-time PCR and western
      blot. Glycosaminoglycan depletion from cartilage explants was determined using a
      1,9-dimethylene blue assay and safranin O staining. RESULTS: FTY720-P
      significantly reduced IL-1beta and TNF-alpha induced expression of iNOS. In
      contrast FTY720-P increased MMP-3 and ADAMTS-5 mRNA expression. Furthermore
      depletion of glycosaminoglycan from cartilage explants by IL-1beta and TNF-alpha
      was significantly enhanced by FTY720-P in an MMP-3 dependent manner. CONCLUSIONS:
      Our results suggest that FTY720 may enhance cartilage degradation in pro
      inflammatory environment.

PMID- 22151891
TI  - Prokinetic effect of a standardized yarrow (Achillea millefolium) extract and its
      constituent choline: studies in the mouse and human stomach.
AB  - BACKGROUND: Functional dyspepsia (FD) is a highly prevalent gastrointestinal
      disorder characterized by alterations in gastric motility. Yarrow (Achillea
      millefolium L., Fam Asteraceae) preparations are traditional remedies used to
      treat dyspeptic complaints. Herein, we investigated the effect of a standardized
      dry water extract obtained from A. millefolium flowering tops (AME) on gastric
      motility. METHODS: The effect of AME on motility was evaluated on the resting
      tone of the isolated gastric antrum and on gastric emptying in vivo (phenol red
      meal method) both in control mice and in the model of cancer chemotherapy
      (cisplatin)-induced gastric abnormalities. KEY RESULTS: The AME contracted mouse
      and human gastric strips and this action was unaffected by hexamethonium and
      tetrodotoxin, but strongly reduced by atropine. Among various chemical
      ingredients in yarrow, choline, but not the flavonoids rutin and apigenin,
      mimicked the action of AME. Furthermore, AME deprived of choline did not exert a
      contractile effect. In vivo, AME stimulated gastric emptying both in control and
      in cisplatin-treated mice, being more active in pathological states. CONCLUSIONS
      & INFERENCES: It is concluded that (i) AME exerts a direct spasmogenic effect on
      gastric antrum; (ii) choline is the chemical ingredient responsible of such
      effect; (iii) the prokinetic effect of AME observed in vivo could provide the
      pharmacological basis underlying its traditional use in the treatment of
      dyspepsia.

PMID- 22151890
TI  - The odds of duplicate gene persistence after polyploidization.
AB  - BACKGROUND: Gene duplication is an important biological phenomenon associated
      with genomic redundancy, degeneration, specialization, innovation, and
      speciation. After duplication, both copies continue functioning when natural
      selection favors duplicated protein function or expression, or when mutations
      make them functionally distinct before one copy is silenced. RESULTS: Here we
      quantify the degree to which genetic parameters related to gene expression,
      molecular evolution, and gene structure in a diploid frog - Silurana tropicalis -
      influence the odds of functional persistence of orthologous duplicate genes in a
      closely related tetraploid species - Xenopus laevis. Using public databases and
      454 pyrosequencing, we obtained genetic and expression data from S. tropicalis
      orthologs of 3,387 X. laevis paralogs and 4,746 X. laevis singletons - the most
      comprehensive dataset for African clawed frogs yet analyzed. Using logistic
      regression, we demonstrate that the most important predictors of the odds of
      duplicate gene persistence in the tetraploid species are the total gene
      expression level and evenness of expression across tissues and development in the
      diploid species. Slow protein evolution and information density (fewer exons,
      shorter introns) in the diploid are also positively correlated with duplicate
      gene persistence in the tetraploid. CONCLUSIONS: Our findings suggest that a
      combination of factors contribute to duplicate gene persistence following whole
      genome duplication, but that the total expression level and evenness of
      expression across tissues and through development before duplication are most
      important. We speculate that these parameters are useful predictors of duplicate
      gene longevity after whole genome duplication in other taxa.

PMID- 22151892
TI  - The comparative biology of diving in two genera of European Dytiscidae
      (Coleoptera).
AB  - Surfacing behaviour is fundamental in the ecology of aquatic air-breathing
      organisms; however, it is only in vertebrates that the evolutionary ecology of
      diving has been well characterized. Here, we explore the diving behaviour of
      dytiscid beetles, a key group of surface-exchanging freshwater invertebrates, by
      comparing the dive responses of 25 taxa (Deronectes and Ilybius spp.) acclimated
      at two temperatures. The allometric slopes of dive responses in these dytiscids
      appear similar to those of vertebrate ectotherms, supporting the notion that
      metabolic mode shapes the evolution of diving performance. In both genera,
      beetles spend more time submerged than on the surface, and surface time does not
      vary with the temperature of acclimation. However, presumably in order to meet
      increased oxygen demand at higher temperatures, Deronectes species increase
      surfacing frequency, whereas Ilybius species decrease dive time, an example of
      'multiple solutions.' Finally, widespread northern species appear to possess
      higher diving performances than their geographically restricted southern
      relatives, something which may have contributed to their range expansion ability.

PMID- 22151893
TI  - Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the
      blood-retinal barrier in a type 2 diabetes animal model.
AB  - AIM: The aim of this study was to evaluate the efficacy of sitagliptin, a
      dipeptidyl peptidase IV inhibitor (DPP-IV), in preventing the deleterious effects
      of diabetes on the blood-retinal barrier in male Zucker Diabetic Fatty (ZDF)
      rats. METHODS: ZDF rats at 20 weeks of age were treated with sitagliptin (10
      mg/kg/day) during 6 weeks. The effect of the drug on glycaemia was assessed by
      evaluating glycated haemoglobin (HbA1c). The content and/or distribution of tight
      junction (TJ) proteins occludin and claudin-5, as well as nitrotyrosine residues,
      interleukin (IL)-1beta, BAX and Bcl-2 was evaluated in the retinas by western
      blotting and/or immunohistochemistry. Retinal cell apoptosis was assessed by the
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)
      assay. The number of CD34+ cells present in peripheral circulation was assessed
      by flow cytometry, and endothelial progenitor cells (EPC) adhesion ability to the
      retinal vessels was evaluated by immunohistochemistry. RESULTS: Sitagliptin
      improved glycaemic control as reflected by a significant decrease in HbA1c levels
      by about 1.2%. Treatment with sitagliptin prevented the changes in the
      endothelial subcellular distribution of the TJ proteins induced by diabetes.
      Sitagliptin also decreased the nitrosative stress, the inflammatory state and
      cell death by apoptosis in diabetic retinas. Diabetic animals presented decreased
      levels of CD34+ cells in the peripheral circulation and decreased adhesion
      ability of EPC to the retinal vessels. Sitagliptin allowed a recovery of the
      number of CD34+ cells present in the bloodstream to levels similar to their
      number in controls and increased the adhesion ability of EPC to the retinal
      vessels. CONCLUSIONS: Sitagliptin prevented nitrosative stress, inflammation and
      apoptosis in retinal cells and exerted beneficial effects on the blood-retinal
      barrier integrity in ZDF rat retinas.

PMID- 22151894
TI  - Rolled-up tubes and cantilevers by releasing SrRuO3-Pr0.7Ca0.3MnO3 nanomembranes.
AB  - Three-dimensional micro-objects are fabricated by the controlled release of
      inherently strained SrRuO3/Pr0.7Ca0.3MnO3/SrRuO3 nanometer-sized trilayers from
      SrTiO3(001) substrates. Freestanding cantilevers and rolled-up microtubes with a
      diameter of 6 to 8 MUm are demonstrated. The etching behavior of the SrRuO3 film
      is investigated, and a selectivity of 1:9,100 with respect to the SrTiO3
      substrate is found. The initial and final strain states of the rolled-up oxide
      layers are studied by X-ray diffraction on an ensemble of tubes. Relaxation of
      the sandwiched Pr0.7Ca0.3MnO3 layer towards its bulk lattice parameter is
      observed as the major driving force for the roll-up of the trilayers. Finally, MU
      diffraction experiments reveal that a single object can represent the ensemble
      proving a good homogeneity of the rolled-up tubes.PACS: 81.07.-b; 68.60.-p;
      68.37.Lp; 81.16.Dn.

PMID- 22151895
TI  - Risk of foot-and-mouth disease for the Pacific NorthWest economic region.
AB  - The paper discusses the risk for an outbreak of foot-and-mouth disease (FMD) in
      the Pacific NortWest Economic Region (PNWER). Topics examined throughout the
      paper include: why PNWER is vulnerable to FMD, risks to Canada and the U.S. for
      the introduction of FMD, response strategies, and preventative measures. These
      topics will identify a number of challenges that region will face if an outbreak
      were to occur including illegal trade, movement of people, livestock movements,
      vaccination, and zoning. There is also a discussion in these topics around
      potential strategies that could be used on both sides of the border to minimize
      the impact of an outbreak both from an animal welfare perspective and from a
      trade and economic perspective.

PMID- 22151896
TI  - Recent trend of clinical features in patients with hepatocellular carcinoma.
AB  - AIM:   In this study, we evaluated the clinical characteristics of hepatocellular
      carcinoma (HCC) because the etiology of HCC has been changing recently. METHODS: 
      Consecutive 1374 HCC patients at our institution from 1995 to 2009 were enrolled
      and clinical characteristics were investigated. RESULTS:   Seventeen percent and
      67% of HCC were related to hepatitis B virus (HBV-HCC) and hepatitis C virus (HCV
      HCC), respectively. Fifteen percent of that was negative for hepatitis B surface
      antigen (HBsAg) and antibody to hepatitis C virus (HCVAb) (NBNC-HCC). HCV-HCC
      tended to decrease and NBNC-HCC tended to increase in recent years. Patients with
      NBNC-HCC and HCV-HCC were significantly older than those with HBV-HCC. The
      complication rates of diabetes mellitus (DM), heavy alcohol consumption,
      hypertension, and hyperlipidemia in NBNC-HCC were significantly higher than those
      in other groups. Furthermore, the platelet counts and body mass index in NBNC-HCC
      were significantly higher than those of other groups. Among 209 NBNC-HCC
      patients, 58 patients underwent hepatic resection in which 29%, 36%, and 35% of
      those were based on non-alcoholic steatohepatitis (NASH), heavy alcohol
      consumption, and unknown etiology, respectively. DM was prevalent especially in
      NASH and heavy alcohol consumption. Cirrhosis was detected in 65%, 81%, and 15%
      in NASH-HCC, heavy alcohol consumption-HCC, and unknown etiology, respectively.
      CONCLUSIONS:   NBNC-HCC has gradually been increasing in recent years. The
      present study elucidated that the presence of NASH and metabolic syndrome were
      important risk factors for NBNC-HCC and suggests that these patients should
      receive surveillance for HCC development.

PMID- 22151897
TI  - MicroRNA-494 suppresses cell proliferation and induces senescence in A549 lung
      cancer cells.
AB  - OBJECTIVES: MicroRNAs (miRNAs) are small functional RNAs that regulate mRNAs for
      degradation or translational suppression. In the present study, we aimed to
      reveal functional importance of miRNA-494 (miR-494) in A549 human lung cancer
      cells. MATERIALS AND METHODS: We established A549 cells that constitutively
      expressed miR-494. Next, we sought to investigate insulin-like growth factor 2
      mRNA-binding protein 1 (IGF2BP1) mRNA as an miR-494 target. For this, we
      constructed a reporter plasmid bearing potential miR-494 binding sequences
      derived from the 3'-untranslated region (3'-UTR) of IGF2BP1 mRNA in the 3'-UTR of
      the luciferase gene. RESULTS: Through comparison between miR-494 expressing cells
      and control cells, we revealed that miR-494 suppressed cell proliferation and
      colony forming activity, and induced senescence. Reporter activity was inhibited
      by miR-494. In addition, IGF2BP1 mRNA levels were down-regulated in A549 cells
      that constitutively expressed miR-494. IGF2BP1 has been shown to bind and
      suppress IGF2 mRNA, and this could be a reason why IGF2BP1 can regulate cell
      function. Therefore, we analysed IGF2 mRNA levels and revealed that IGF2 was up
      regulated in A549 cells that constitutively expressed miR-494. Finally, elevated
      IGF2 mRNA levels in A549 cells that constitutively expressed miR-494 were
      suppressed to basal level by an miR-494 inhibitor. CONCLUSIONS: Taken together,
      IGF2BP1 and its downstream target IGF2 could be a crucial axis for miR-494 in
      regulation of the destiny of A549 cells.

PMID- 22151898
TI  - Risk factors for pre-eclampsia in Mulago Hospital, Kampala, Uganda.
AB  - OBJECTIVE: Pre-eclampsia contributes significantly to maternal, foetal and
      neonatal morbidity and mortality. The risk factors for pre-eclampsia have not
      been well documented in Uganda. In this paper, we describe the risk factors for
      pre-eclampsia in women attending antenatal clinics at Mulago Hospital, Kampala.
      METHODS: This casecontrol study was conducted from 1st May 2008 to 1st May 2009.
      207 women with pre-eclampsia were the cases, and 352 women with normal pregnancy
      were the controls. The women were 15-39 years old, and their gestational ages
      were 20 weeks or more. They were interviewed about their socio-demographic
      characteristics, past medical history and, their past and present obstetric
      performances. RESULTS: The risk factors were low plasma vitamin C (OR 3.19, 95%
      CI: 1.54-6.61), low education level (OR 1.67, 95% CI: 1.12-2.48), chronic
      hypertension (OR 2.29, 95% CI 1.12-4.66), family history of hypertension (OR
      2.25, 95% CI: 1.53-3.31) and primiparity (OR 2.76, 95% CI: 1.84-4.15) and para>=5
      (3.71, 95% CI:1.84-7.45). CONCLUSION: The risk factors identified are similar to
      what has been found elsewhere. Health workers need to identify women at risk of
      pre-eclampsia and manage them appropriately so as to prevent the maternal and
      neonatal morbidity and mortality associated with this condition.

PMID- 22151899
TI  - Laryngo-tracheo-oesophageal clefts.
AB  - A laryngo-tracheo-esophageal cleft (LC) is a congenital malformation
      characterized by an abnormal, posterior, sagittal communication between the
      larynx and the pharynx, possibly extending downward between the trachea and the
      esophagus. The estimated annual incidence of LC is 1/10,000 to 1/20,000 live
      births, accounting for 0.2% to 1.5% of congenital malformations of the larynx.
      These incidence rates may however be underestimated due to difficulty in
      diagnosing minor forms and a high mortality rate in severe forms. A slightly
      higher incidence has been reported in boys than in girls. No specific geographic
      distribution has been found. Depending on the severity of the malformation,
      patients may present with stridor, hoarse cry, swallowing difficulties,
      aspirations, cough, dyspnea and cyanosis through to early respiratory distress.
      Five types of laryngo-tracheo-esophageal cleft have been described based on the
      downward extension of the cleft, which typically correlates with the severity of
      symptoms: Type 0 laryngo-tracheo-esophageal cleft to Type 4 laryngo-tracheo
      esophageal cleft. LC is often associated with other congenital
      abnormalities/anomalies (16% to 68%), mainly involving the gastro-intestinal
      tract, which include laryngomalacia, tracheo-bronchial dyskinesia, tracheo
      bronchomalacia (mostly in types 3 and 4), and gastro-esophageal reflux disease
      (GERD). The syndromes most frequently associated with an LC are Opitz/BBB
      syndrome, Pallister Hall syndrome, VACTERL/VATER association, and CHARGE
      syndrome. Laryngeal clefts result from failure of fusion of the posterior cricoid
      lamina and abnormal development of the tracheo-esophageal septum. The causes of
      the embryological developmental anomalies leading to LC are not known but are
      thought to be multifactorial. LC appears to be mostly sporadic although some
      familial cases with suspected autosomal dominant transmission have been reported.
      The age of diagnosis depends mainly on the severity of the clinical symptoms and
      therefore on the extent of the LC. Diagnosis is made either based on clinical
      manifestations or on investigations, such as endoscopy, X-ray, CT scan, performed
      for other conditions. Differential diagnoses include tracheo-bronchial fistula,
      gastro-esophageal reflux disease and neurological swallowing disorders, as well
      as laryngomalacia and laryngeal palsy. Prenatal diagnosis of LC has never been
      reported, although associated anomalies may be detected on fetal ultrasonography.
      Once the cleft is diagnosed, it is essential to determine its length to orient
      the management and treatment approach. Management involves maintenance of
      satisfactory ventilation, prevention of secondary pulmonary complications as a
      result of repeated aspirations, and adequate feeding. Endotracheal intubation may
      be required for respiratory distress in severe cases. Treatment requires
      endoscopic or external surgery to close the cleft. Surgery should be performed as
      early as possible to avoid complications related to aspiration and gastric
      reflux, except in type 0 and type 1 cases in which conservative measures must
      first be attempted. The prognosis is variable depending on the severity of the LC
      and associated malformations. Early diagnosis and appropriate treatment and
      management help to reduce mortality and morbidity.

PMID- 22151900
TI  - Recurrence of type 1 diabetes after simultaneous pancreas-kidney transplantation
      in the absence of GAD and IA-2 autoantibodies.
AB  - We report herein the patterns of type 1 diabetes recurrence in a simultaneous
      pancreas-kidney transplant (SPK) recipient, in the absence of rejection. A 38
      year-old female underwent SPK for end-stage nephropathy secondary to type 1
      diabetes. Fasting blood glucose, HbA1c, fructosamine, C-peptide and
      autoantibodies (GAD-65, IA-2) were monitored throughout follow-up. At 3.5 years
      post-SPK, HbA1c and fructosamine increased sharply, indicating loss of perfect
      metabolic control, despite C-peptide levels in the normal-high range. Exogenous
      insulin was restarted 4 months later. C-peptide levels abruptly fell and became
      undetectable at 5.5 years. Autoantibody levels, which were undetectable at the
      time of SPK, never converted to positivity. Pancreas retranspantation was
      performed at 6 years. The failed pancreas graft had a normal macroscopic
      appearance. On histology, there were no signs of cellular or humoral rejection in
      the kidney or pancreas. A selective peri-islet lymphocytic infiltrate was
      observed, together with near-total destruction of beta cells. At 2.5 years post
      retransplantation, pancreatic graft function is perfect. This observation
      indicates unequivocally that pancreas graft can be lost to recurrence of type 1
      diabetes in the absence of rejection. GAD-65 and IA-2 autoantibodies are not
      reliable markers of autoimmunity recurrence.

PMID- 22151901
TI  - The gene normalization task in BioCreative III.
AB  - BACKGROUND: We report the Gene Normalization (GN) challenge in BioCreative III
      where participating teams were asked to return a ranked list of identifiers of
      the genes detected in full-text articles. For training, 32 fully and 500
      partially annotated articles were prepared. A total of 507 articles were selected
      as the test set. Due to the high annotation cost, it was not feasible to obtain
      gold-standard human annotations for all test articles. Instead, we developed an
      Expectation Maximization (EM) algorithm approach for choosing a small number of
      test articles for manual annotation that were most capable of differentiating
      team performance. Moreover, the same algorithm was subsequently used for
      inferring ground truth based solely on team submissions. We report team
      performance on both gold standard and inferred ground truth using a newly
      proposed metric called Threshold Average Precision (TAP-k). RESULTS: We received
      a total of 37 runs from 14 different teams for the task. When evaluated using the
      gold-standard annotations of the 50 articles, the highest TAP-k scores were
      0.3297 (k=5), 0.3538 (k=10), and 0.3535 (k=20), respectively. Higher TAP-k scores
      of 0.4916 (k=5, 10, 20) were observed when evaluated using the inferred ground
      truth over the full test set. When combining team results using machine learning,
      the best composite system achieved TAP-k scores of 0.3707 (k=5), 0.4311 (k=10),
      and 0.4477 (k=20) on the gold standard, representing improvements of 12.4%,
      21.8%, and 26.6% over the best team results, respectively. CONCLUSIONS: By using
      full text and being species non-specific, the GN task in BioCreative III has
      moved closer to a real literature curation task than similar tasks in the past
      and presents additional challenges for the text mining community, as revealed in
      the overall team results. By evaluating teams using the gold standard, we show
      that the EM algorithm allows team submissions to be differentiated while keeping
      the manual annotation effort feasible. Using the inferred ground truth we show
      measures of comparative performance between teams. Finally, by comparing team
      rankings on gold standard vs. inferred ground truth, we further demonstrate that
      the inferred ground truth is as effective as the gold standard for detecting good
      team performance.

PMID- 22151902
TI  - Effects of Wnt3A and mechanical load on cartilage chondrocyte homeostasis.
AB  - INTRODUCTION: Articular cartilage functions in withstanding mechanical loads and
      provides a lubricating surface for frictionless movement of joints.
      Osteoarthritis, characterised by cartilage degeneration, develops due to the
      progressive erosion of structural integrity and eventual loss of functional
      performance. Osteoarthritis is a multi-factorial disorder; two important risk
      factors are abnormal mechanical load and genetic predisposition. A single
      nucleotide polymorphism analysis demonstrated an association of hip
      osteoarthritis with an Arg324Gly substitution mutation in FrzB, a Wnt antagonist.
      The purpose of this study was two-fold: to assess whether mechanical stimulation
      modulates beta-catenin signalling and catabolic gene expression in articular
      chondrocytes, and further to investigate whether there is an interplay of
      mechanical load and Wnt signalling in mediating a catabolic response. METHODS:
      Chondrocytes were pre-stimulated with recombinant Wnt3A for 24 hours prior to the
      application of tensile strain (7.5%, 1 Hz) for 30 minutes. Activation of Wnt
      signalling, via beta-catenin nuclear translocation and downstream effects
      including the transcriptional activation of c-jun, c-fos and Lef1, markers of
      chondrocyte phenotype (type II collagen (col2a1), aggrecan (acan), SOX9) and
      catabolic genes (MMP3, MMP13, ADAMTS-4, ADAMTS-5) were assessed. RESULTS:
      Physiological tensile strain induced col2a1, acan and SOX9 transcription. Load
      induced acan and SOX9 expression were repressed in the presence of Wnt3A. Load
      induced partial beta-catenin nuclear translocation; there was an additive effect
      of load and Wnt3A on beta-catenin distribution, with both extensive localisation
      in the nucleus and cytoplasm. Immediate early response (c-jun) and catabolic
      genes (MMP3, ADAMTS-4) were up-regulated in Wnt3A stimulated chondrocytes. With
      load and Wnt3A there was an additive up-regulation of c-fos, MMP3 and ADAMTS-4
      transcription, whereas there was a synergistic interplay on c-jun, Lef1 and
      ADAMTS-5 transcription. CONCLUSION: Our data suggest that load and Wnt, in
      combination, can repress transcription of chondrocyte matrix genes, whilst
      enhancing expression of catabolic mediators. Future studies will investigate the
      respective roles of abnormal loading and genetic predisposition in mediating
      cartilage degeneration.

PMID- 22151903
TI  - Diffuse bronchiolitis pattern on a computed tomography scan as a presentation of
      pulmonary tumor thrombotic microangiopathy: a case report.
AB  - INTRODUCTION: Pulmonary tumor thrombotic microangiopathy is a rare complication
      of malignant diseases. The diagnosis is extremely difficult and is most often
      performed after death. Invariably, patients develop acute pulmonary hypertension
      causing right heart failure, shortness of breath and death in a few days. We
      describe the clinical and radiological findings of a patient who presented with
      this complication. CASE PRESENTATION: A 28-year-old Caucasian woman with a
      previous history of pelvic tumor resection two months previously, suggestive of
      metastatic adenocarcinoma, presented with intense shortness of breath. A computed
      tomography scan showed signs of acute cor pulmonale and diffuse nodular opacities
      associated with a tree-in-bud pattern disseminated through her lungs, suggestive
      of bronchiolitis. Our patient's condition worsened and she underwent a surgical
      biopsy. Pathologic analysis of the biopsied specimens revealed pulmonary tumor
      thrombotic microangiopathy. Our patient's tumor evolved from a gastric origin
      (Krukenberg tumor). She underwent progressive clinical deterioration and died
      less than 24 hours after the biopsy. None of the cases described previously in
      the literature had diffuse centrilobular nodular opacities associated with a tree
      in-bud pattern disseminated through the lungs, as in our case. CONCLUSION:
      Pulmonary tumor thrombotic microangiopathy should be considered in cancer
      patients with rapidly progressing dyspnea, chest computed tomography findings
      compatible with pulmonary hypertension and typical findings of inflammatory
      bronchiolitis.

PMID- 22151904
TI  - The four types of Tregs in malignant lymphomas.
AB  - Regulatory T cells (Tregs) are a specialized subpopulation of CD4(+) T cells,
      which act to suppress the activation of other immune cells. Tregs represent
      important modulators for the interaction between lymphomas and host
      microenvironment. Lymphomas are a group of serious and frequently fatal malignant
      diseases of lymphocytes. Recent studies revealed that some lymphoma T cells might
      adopt a Treg profile. Assessment of Treg phenotypes and genotypes in patients may
      offer prediction of outcome in many types of lymphomas including diffuse large B
      cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, and Hodgkin's
      lymphoma. Based on characterized roles of Tregs in lymphomas, we can categorize
      the various roles into four groups: (a) suppressor Tregs; (b) malignant Tregs;
      (c) direct tumor-killing Tregs; and (d) incompetent Tregs. The classification
      into four groups is significant in predicting prognosis and designing Tregs-based
      immunotherapies for treating lymphomas. In patients with lymphomas where Tregs
      serve either as suppressor Tregs or malignant Tregs, anti-tumor cytotoxicity is
      suppressed thus decreased numbers of Tregs are associated with a good prognosis.
      In contrast, in patients with lymphomas where Tregs serve as tumor-killing Tregs
      and incompetent Tregs, anti-tumor cytotoxicity is enhanced or anti-autoimmune
      Tregs activities are weakened thus increased numbers of Tregs are associated with
      a good prognosis and reduced numbers of Tregs are associated with a poor
      prognosis. However, the mechanisms underlying the various roles of Tregs in
      patients with lymphomas remain unknown. Therefore, further research is needed in
      this regard as well as the utility of Tregs as prognostic factors and therapy
      strategies in different lymphomas.

PMID- 22151905
TI  - Using clinical pathways to aid in the diagnosis of necrotizing soft tissue
      infections synthesis of evidence.
AB  - BACKGROUND: Necrotizing soft tissue infections (NSTIs) are rare, rapidly
      spreading infections that occur in the soft tissue compartments. The mortality
      rate is high and has been found to decrease if patients are treated early and
      aggressively with surgical debridement and broad-spectrum antibiotics.
      Unfortunately these infections present similarly to other types of skin and soft
      tissue infections (SSTIs) making diagnosis difficult. AIMS: This paper reviews
      the evidence surrounding the early diagnosis of NSTIs. This was used to develop a
      clinical practice guideline (CPG) for implementation in the emergency department
      (ED) setting to assist the provider in distinguishing NSTIs from SSTIs to
      potentially decrease the time from presentation to diagnosis. METHODS: A review
      of the literature was performed. Studies were identified and critiqued by two
      reviewers independently for clinical relevance, study design, and statistical
      analysis. RESULTS: Signs and symptoms, or "hard signs," associated with NSTIs
      include: pain out of proportion to the exam, rapidly spreading infection,
      presence of bullae, skin ecchymosis or sloughing, gas in the tissues, skin
      anesthesia, edema extending beyond the erythema, and symptoms of sepsis.
      Unfortunately only 43% of the patients with an NSTI will present with these
      signs. Studies have found an association between laboratory values and NSTIs with
      the most commonly associated findings being leukocytosis, azotemia, and
      hyponatremia. Using these complimentary clinical and laboratory values, the
      Laboratory Risk Indicator for NECrotizing fasciitis (LRINEC) score is an emerging
      tool that providers can use to determine the risk of an NSTI. A clinical pathway
      was developed and implemented in the ED for all patients presenting with an SSTI
      to assist providers in confirming or negating the presence of an NSTI.
      IMPLICATION FOR PRACTICE: Educating ED providers about the signs, symptoms, and
      laboratory findings associated with NSTIs will lead to earlier diagnosis and
      treatment and decreased morbidity and mortality.

PMID- 22151906
TI  - Prevalence of general and abdominal obesity in the adult population of Spain,
      2008-2010: the ENRICA study.
AB  - This is the first study to report the prevalence of general obesity and abdominal
      obesity (AO) in the adult population of Spain based on measurements of weight,
      height and waist circumference. The data are taken from the ENRICA study, a cross
      sectional study carried out between June 2008 and October 2010 in 12,883
      individuals representative of the non-institutionalized population on Spain aged
      18 years and older. Anthropometry was performed under standardized conditions in
      the households by trained interviewers. Overweight was considered as body mass
      index (BMI) 25-29.9 kg m(-2) , and obesity as BMI >= 30 kg m(-2) . AO was defined
      as waist circumference >102 cm in men and >88 cm in women. The prevalence of
      obesity was 22.9% (24.4% in men and 21.4% in women). About 36% of adults had AO
      (32% of men and 39% of women). The frequency of obesity and of AO increased with
      age and affected, respectively, 35 and 62% of persons aged 65 and over. The
      frequency of obesity and AO decreased with increasing educational level. For
      example, 29% of women with primary education or less had obesity vs. only 11% of
      those with university studies. The prevalence of obesity was very high in the
      Canary Islands and in the south of Spain.

PMID- 22151907
TI  - Incidence and modes of presentation of childhood type 1 diabetes mellitus in
      Malta between 2006 and 2010.
AB  - AIM: To assess the incidence and mode of presentation of type 1 diabetes mellitus
      (T1DM) in children and adolescents younger than 14 yr of age between January 2006
      and December 2010 in Malta. METHODS: A nationwide prospective study which
      collected data from newly diagnosed T1DM children who presented to the only
      paediatric diabetes team available in Malta. The degree of ascertainment was
      estimated to be 100%. Incidence rates by age group and year were estimated using
      real values of diagnosed patients and population statistics. Trend analysis was
      carried out using Poisson's regression analysis. RESULTS: From 2006 to 2010, 81
      children below the age of 14 yr were diagnosed with T1DM for the first time. The
      age- and sex-standardised incidence rate was 21.86/100,000 children/yr. The
      estimated annual increase in incidence was 21.8%. Compared to data collected
      retrospectively between 1996-2001, the incidence has increased threefold between
      2006 and 2010. Generally, the incidence rate was highest in the 5-9 yr age group,
      followed by the 0-4 yr age group and finally the10-14 yr age group. However, the
      highest annual increase occurred in the 0-4 yr age group at 39% per year, closely
      followed by 5-9 yr age group at 31% per year. In the 10-14 yr age group, the
      trend appeared to show a reduction in incidence. The proportion of patients
      presenting in diabetic ketoacidosis (DKA) was high at 41%. CONCLUSION: In Malta,
      the number of children/adolescents with T1DM has been rising at a faster rate
      than expected, and a distinct shift to younger age at onset has been observed.
      DKA rate at presentation is still high in Maltese children.

PMID- 22151908
TI  - The impact of phosphate scarcity on pharmaceutical protein production in S.
      cerevisiae: linking transcriptomic insights to phenotypic responses.
AB  - BACKGROUND: The adaptation of unicellular organisms like Saccharomyces cerevisiae
      to alternating nutrient availability is of great fundamental and applied
      interest, as understanding how eukaryotic cells respond to variations in their
      nutrient supply has implications spanning from physiological insights to
      biotechnological applications. RESULTS: The impact of a step-wise restricted
      supply of phosphate on the physiological state of S. cerevisiae cells producing
      human Insulin was studied. The focus was to determine the changes within the
      global gene expression of cells being cultured to an industrially relevant high
      cell density of 33 g/l cell dry weight and under six distinct phosphate
      concentrations, ranging from 33 mM (unlimited) to 2.6 mM (limited). An increased
      flux through the secretory pathway, being induced by the PHO circuit during low
      P(i) supplementation, proved to enhance the secretory production of the
      heterologous protein. The re-distribution of the carbon flux from biomass
      formation towards increased glycerol production under low phosphate led to
      increased transcript levels of the insulin gene, which was under the regulation
      of the TPI1 promoter. CONCLUSIONS: Our study underlines the dynamic character of
      adaptive responses of cells towards a change in their nutrient access. The
      gradual decrease of the phosphate supply resulted in a step-wise modulated
      phenotypic response, thereby alternating the specific productivity and the
      secretory flux. Our work emphasizes the importance of reduced phosphate supply
      for improved secretory production of heterologous proteins.

PMID- 22151909
TI  - Rationale and study design for a randomised controlled trial to reduce sedentary
      time in adults at risk of type 2 diabetes mellitus: project stand (Sedentary Time
      ANd diabetes).
AB  - BACKGROUND: The rising prevalence of Type 2 Diabetes Mellitus (T2DM) is a major
      public health problem. There is an urgent need for effective lifestyle
      interventions to prevent the development of T2DM. Sedentary behaviour (sitting
      time) has recently been identified as a risk factor for diabetes, often
      independent of the time spent in moderate-to-vigorous physical activity. Project
      STAND (Sedentary Time ANd Diabetes) is a study which aims to reduce sedentary
      behaviour in younger adults at high risk of T2DM. METHODS/DESIGN: A reduction in
      sedentary time is targeted using theory driven group structured education. The
      STAND programme is subject to piloting and process evaluation in line with the
      MRC framework for complex interventions. Participants are encouraged to self
      monitor and self-regulate their behaviour. The intervention is being assessed in
      a randomised controlled trial with 12 month follow up. Inclusion criteria are a)
      aged 18-40 years with a BMI in the obese range; b) 18-40 years with a BMI in the
      overweight range plus an additional risk factor for T2DM. Participants are
      randomised to the intervention (n = 89) or control (n = 89) arm. The primary
      outcome is a reduction in sedentary behaviour at 12 months as measured by an
      accelerometer (count < 100/min). Secondary outcomes include physical activity,
      sitting/lying time using the ActivPAL posture monitor, fasting and 2 h oral
      glucose tolerance test, lipids, inflammatory biomarkers, body weight, waist
      circumference, blood pressure, illness perceptions, and efficacy beliefs for
      behaviour change. CONCLUSIONS: This is the first UK trial to address sedentary
      behaviour change in a population of younger adults at risk of T2DM. The results
      will provide a platform for the development of a range of future
      multidisciplinary interventions in this rapidly expanding high-risk population.
      TRIAL REGISTRATION: Current controlled trials ISRCTN08434554, MRC project 91409.

PMID- 22151910
TI  - Evidence for intron length conservation in a set of mammalian genes associated
      with embryonic development.
AB  - BACKGROUND: We carried out an analysis of intron length conservation across a
      diverse group of nineteen mammalian species. Motivated by recent research
      suggesting a role for time delays associated with intron transcription in gene
      expression oscillations required for early embryonic patterning, we searched for
      examples of genes that showed the most extreme conservation of total intron
      content in mammals. RESULTS: Gene sets annotated as being involved in pattern
      specification in the early embryo or containing the homeobox DNA-binding domain,
      were significantly enriched among genes with highly conserved intron content. We
      used ancestral sequences reconstructed with probabilistic models that account for
      insertion and deletion mutations to distinguish insertion and deletion events on
      lineages leading to human and mouse from their last common ancestor. Using a
      randomization procedure, we show that genes containing the homeobox domain show
      less change in intron content than expected, given the number of insertion and
      deletion events within their introns. CONCLUSIONS: Our results suggest selection
      for gene expression precision or the existence of additional development
      associated genes for which transcriptional delay is functionally significant.

PMID- 22151912
TI  - A longitudinal study on BIO14.6 hamsters with dilated cardiomyopathy: micro
      echocardiographic evaluation.
AB  - BACKGROUND: In recent years, several new technologies for small-animal imaging
      have been developed. In particular, the use of ultrasound in animal imaging has
      focused on the investigation of accessible biological structures such as the
      heart, of which it provides a morphological and functional assessment. The
      purpose of this study was to investigate the role of micro-ultrasonography (MU
      US) in a longitudinal study on BIO14.6 cardiomyopathic hamsters treated with gene
      therapy. METHODS: Thirty hamsters were divided into three groups (n = 10): Group
      I, untreated BIO 14.6 hamsters; Group II, BIO 14.6 hamsters treated with gene
      therapy; Group III, untreated wild type (WT) hamsters. All hamsters underwent
      serial MU-US sessions and were sacrificed at predetermined time points. RESULTS:
      MU-US revealed: in Group I, progressive dilation of the left ventricle with a
      change in heart morphology from an elliptical to a more spherical shape, altered
      configuration of the mitral valve and subvalvular apparatus, and severe reduction
      in ejection fraction; in Group II, mild decrease in contractile function and
      ejection fraction; in Group III, normal cardiac chamber morphology and function.
      There was a negative correlation between the percentage of fibrosis observed at
      histology and the ejection fraction obtained on MU-echocardiography (Spearman r: 
      0.839; p < 0.001). CONCLUSIONS: Although histological examination remains
      indispensable for a conclusive diagnosis, high-frequency MU-echocardiography,
      thanks to the high spatial and contrast resolution, can be considered sufficient
      for monitoring therapeutic efficacy and/or the progression of dilated
      cardiomyopathy, providing an alternative tool for repeatable and noninvasive
      evaluation.

PMID- 22151913
TI  - Protease activated receptor 4 status of mast cells in post infectious irritable
      bowel syndrome.
AB  - BACKGROUND: Growing evidence suggests that protease activated receptors (PARs)
      are mediators of persistent neuropathic pain, but their possible function as
      mediators in patients with post infectious irritable bowel syndrome (PI-IBS)
      remains to be further explored. This article aims to investigate the expression
      of PAR(2) and PAR(4) in the colonic mucosa of patients with PI-IBS, focusing on
      correlation with mast cell activation status. METHODS: A total of 17 normal
      controls and 23 patients with PI-IBS volunteered the study. The expression and
      localization of PAR(2) and PAR(4) were investigated by RT-PCR and
      immunohistochemistry, and the expression of PAR(2) and PAR(4) in the mast cells
      was examined using double-immunofluorescence staining. KEY RESULTS: The
      immunohistochemical study revealed that epithelial and submucosal cells showed
      immunoreactivity for both PAR(2) and PAR(4). Protease activated receptor 4 mRNA
      expression and immunoreactivity were down-regulated in PI-IBS compared with the
      control group. Specifically, a reduced immunoreactivity for PAR(4) was observed
      in mast cells of PI-IBS compared with normal controls, whereas there are no
      significant differences shown in PAR(2) between the PI-IBS and the control group.
      It is also found that the PAR(4) immunoreactivity decreases, while the activity
      of mast cells increases in PI-IBS rather than normal controls. CONCLUSIONS &
      INFERENCES: This study outlines the down-regulation of PAR(4) in the mast cells
      of PI-IBS. It could be of considerable interests in understanding the mechanisms
      involved in the persistent colonic hypersensitivity and their potential role as
      therapeutic targets for PI-IBS.

PMID- 22151911
TI  - Association of laterality and size of perfusion lesions on neurological deficit
      in acute supratentorial stroke.
AB  - BACKGROUND: The influence of lesion size and laterality on each component of the
      National Institutes of Health Stroke Scale has not been delineated. The objective
      of this study was to use perfusion-weighted imaging to characterize the
      association of ischaemic volume and laterality on each component item and the
      total score of the <National Institutes of Health Stroke Scale. METHODS: We
      analysed consecutive right-handed patients with first-ever supratentorial acute
      ischaemic strokes who underwent acute perfusion-weighted imaging at a single
      centre. Perfusion deficits were defined as mean transit time > 10 s. Ordinal
      regression was used to clarify the relationship between ischaemic volume,
      laterality, and <National Institutes of Health Stroke Scale scores. RESULTS:
      Among 111 patients, 58 were left-hemisphere stroke, and 53 right-hemisphere
      stroke. Median ischaemic volume was 53 ml in left-hand stroke and 65 ml in right
      hand stroke and median total National Institutes of Health Stroke Scale was 10 in
      left-hand stroke and eight in right-hand stroke. For individual National
      Institutes of Health Stroke Scale items, ischaemic volume correlated most closely
      with commands and visual field and most weakly with ataxia and neglect. Left-hand
      stroke predicted higher scores of total National Institutes of Health Stroke
      Scale and National Institutes of Health Stroke Scale items of questions,
      commands, right limb weakness, and language. Right-hand stroke predicted higher
      scores of left limb weakness and extinction. CONCLUSIONS: Larger perfusion
      defects contribute to higher scores on the total and most individual items of the
      National Institutes of Health Stroke Scale. However, lesion laterality
      contributes substantially to half the item scores, with greater association of
      left than right-brain side. These findings indicate that imaging-deficit
      correlations will be improved by designating lesions into an atlas, taking into
      account side in addition to size.

PMID- 22151914
TI  - Classification of rhythmic locomotor patterns in electromyographic signals using
      fuzzy sets.
AB  - BACKGROUND: Locomotor control is accomplished by a complex integration of neural
      mechanisms including a central pattern generator, spinal reflexes and supraspinal
      control centres. Patterns of muscle activation during walking exhibit an
      underlying structure in which groups of muscles seem to activate in united
      bursts. Presented here is a statistical approach for analyzing Surface
      Electromyography (SEMG) data with the goal of classifying rhythmic "burst"
      patterns that are consistent with a central pattern generator model of locomotor
      control. METHODS: A fuzzy model of rhythmic locomotor patterns was optimized and
      evaluated using SEMG data from a convenience sample of four able-bodied
      individuals. As well, two subjects with pathological gait participated: one with
      Parkinson's Disease, and one with incomplete spinal cord injury. Subjects walked
      overground and on a treadmill while SEMG was recorded from major muscles of the
      lower extremities. The model was fit to half of the recorded data using non
      linear optimization and validated against the other half of the data. The
      coefficient of determination, R(2), was used to interpret the model's goodness of
      fit. RESULTS: Using four fuzzy burst patterns, the model was able to explain
      approximately 70-83% of the variance in muscle activation during treadmill gait
      and 74% during overground gait. When five burst functions were used, one function
      was found to be redundant. The model explained 81-83% of the variance in the
      Parkinsonian gait, and only 46-59% of the variance in spinal cord injured gait.
      CONCLUSIONS: The analytical approach proposed in this article is a novel way to
      interpret multichannel SEMG signals by reducing the data into basic rhythmic
      patterns. This can help us better understand the role of rhythmic patterns in
      locomotor control.

PMID- 22151915
TI  - Therapeutic and toxicologic evaluation of anti-lipogenic agents in cancer cells
      compared with non-neoplastic cells.
AB  - Fatty acid synthase (FASN), a multi-enzyme complex, is involved in lipid
      biosynthesis. FASN is over-expressed in different types of cancers and is being
      widely investigated for its role in cancer progression, diagnosis and therapy.
      Here, three inhibitors targeting different domains of FASN--cerulenin, triclosan
      and orlistat--were evaluated for their anti-proliferative efficacy in ocular
      cancer, retinoblastoma (RB) cells and their toxicity (if any) in normal cells.
      FASN inhibitors were tested in cultured retinoblastoma Y79 cells, normal
      fibroblast (3T3) and Muller glial (MIOM1) cells. Cell viability was determined by
      MTT-based assay, and IC(50) (50% inhibitory concentration) of the FASN inhibitors
      was calculated in neoplastic and non-neoplastic cells. The IC(50) after 48 and 96
      hr of incubation with the three anti-FASN agents showed that cerulenin, triclosan
      and orlistat inhibited retinoblastoma cell proliferation in a dose- and time
      dependent manner. The cancer cells exhibited differential dose- and time
      dependent response/sensitivities to cerulenin, triclosan and orlistat. The 48-hr
      neoplastic IC(50) dosages were, however, not toxic to the normal cells. These
      findings were confirmed by phase-contrast microscopic assessment of cell
      morphology. Therapeutic index (TI) was calculated as a ratio of the IC(50) normal
      cells, to the IC(50) neoplastic cells. Relative to normal MIOM1 cells, TI was
      9.18 for cerulenin, while 5.32 for triclosan and 1.72 for orlistat. The TI
      computed relative to 3T3 cells was 28.64, 7.10 and 2.58 for cerulenin, triclosan
      and orlistat, respectively. DNA fragmentation analysis suggests that FASN
      inhibitors induced apoptotic DNA damage in retinoblastoma cells. Thus, FASN
      inhibition can be an effective strategy in retinoblastoma therapy.

PMID- 22151916
TI  - Evolution of starvation resistance in Drosophila melanogaster: measurement of
      direct and correlated responses to artificial selection.
AB  - Laboratory selection for resistance to starvation has been conducted under
      relatively controlled conditions to investigate direct and correlated responses
      to artificial selection. With regard to starvation resistance, there are three
      physiological routes by which the trait can evolve: resource accumulation, energy
      conservation and starvation tolerance. A majority of energetic compounds and
      macromolecules including triglycerides, trehalose and other sugars, and soluble
      protein increased in abundance as a result of selection. Movement was
      additionally investigated with selected males moving less than control males and
      selected females exhibiting a similar response to selection. Results obtained
      from this study supported two of the possible evolutionary mechanisms for
      adaptation to starvation: energy compound storage and conservation. If the
      response to selection is based on an evolutionarily conserved pattern of genetic
      correlations (elevated lipid, elevated sugars and reduced movement), then the
      response to selection is medically relevant and the genetic architecture should
      be investigated in depth.

PMID- 22151918
TI  - Cucurbitacin B inhibits 12-O-tetradecanoylphorbol 13-acetate-induced invasion and
      migration of human hepatoma cells through inactivating mitogen-activated protein
      kinase and PI3K/Akt signal transduction pathways.
AB  - AIM:   Cucurbitacin B (CuB) is an active component isolated from various plants
      used as folk medicine in Asian countries and has shown diverse antitumor
      activities. There is, however, no documented effect of CuB on the migration and
      invasion of human hepatoma cells yet. The purpose of this study was to assess the
      effect of CuB on the migration and invasion of hepatoma cells and to explore the
      possible mechanism. METHODS:   Human hepatoma cell lines HepG2 and BEL-7402 were
      used for the study. Effects of CuB on cancer cell migration and invasion were
      evaluated in vitro with wound healing and transwell assays. The effect of CuB on
      the expression of matrix metalloproteinase (MMP)-9, mitogen-activated protein
      kinases (MAPKs), Akt, nuclear factor-kappaB (NF-kappaB), c-Fos and c-Jun was
      investigated with gelatin zymography and/or western blotting. RESULTS:  
      Cucurbitacin B has significantly suppressed 12-O-tetradecanoylphorbol 13-acetate
      (TPA)-induced cell invasion and migration in a concentration-dependent manner,
      which was accompanied with suppression of TPA-induced MMP-9 expression through
      inactivation of phosphorylation of extracellular signal-regulated kinase (ERK)
      1/2, p38 and Akt. In the nucleus, it has also strongly suppressed TPA-stimulated
      expression of NF-kappaB, c-Jun and c-Fos. CONCLUSION:   Cucurbitacin B has a
      potential value for suppressing metastasis of human hepatoma cells through
      suppressing the expression of MMP-9.

PMID- 22151917
TI  - De novo assembly of Euphorbia fischeriana root transcriptome identifies
      prostratin pathway related genes.
AB  - BACKGROUND: Euphorbia fischeriana is an important medicinal plant found in
      Northeast China. The plant roots contain many medicinal compounds including 12
      deoxyphorbol-13-acetate, commonly known as prostratin that is a phorbol ester
      from the tigliane diterpene series. Prostratin is a protein kinase C activator
      and is effective in the treatment of Human Immunodeficiency Virus (HIV) by acting
      as a latent HIV activator. Latent HIV is currently the biggest limitation for
      viral eradication. The aim of this study was to sequence, assemble and annotate
      the E. fischeriana transcriptome to better understand the potential biochemical
      pathways leading to the synthesis of prostratin and other related diterpene
      compounds. RESULTS: In this study we conducted a high throughput RNA-seq approach
      to sequence the root transcriptome of E. fischeriana. We assembled 18,180
      transcripts, of these the majority encoded protein-coding genes and only 17
      transcripts corresponded to known RNA genes. Interestingly, we identified 5,956
      protein-coding transcripts with high similarity (> = 75%) to Ricinus communis, a
      close relative to E. fischeriana. We also evaluated the conservation of E.
      fischeriana genes against EST datasets from the Euphorbeacea family, which
      included R. communis, Hevea brasiliensis and Euphorbia esula. We identified a
      core set of 1,145 gene clusters conserved in all four species and 1,487 E.
      fischeriana paralogous genes. Furthermore, we screened E. fischeriana transcripts
      against an in-house reference database for genes implicated in the biosynthesis
      of upstream precursors to prostratin. This identified 24 and 9 candidate
      transcripts involved in the terpenoid and diterpenoid biosyntehsis pathways,
      respectively. The majority of the candidate genes in these pathways presented
      relatively low expression levels except for 1-hydroxy-2-methyl-2-(E)-butenyl 4
      diphosphate synthase (HDS) and isopentenyl diphosphate/dimethylallyl diphosphate
      synthase (IDS), which are required for multiple downstream pathways including
      synthesis of casbene, a proposed precursor to prostratin. CONCLUSION: The
      resources generated in this study provide new insights into the upstream pathways
      to the synthesis of prostratin and will likely facilitate functional studies
      aiming to produce larger quantities of this compound for HIV research and/or
      treatment of patients.

PMID- 22151919
TI  - Translational prospects for cytokines in 2011. Abstracts of the Kitasato
      Symposium 2011. Potsdam, Germany. September 22-23, 2011.

PMID- 22151920
TI  - The association between allogeneic perioperative blood transfusion on tumour
      recurrence and survival in patients with advanced ovarian cancer.
AB  - OBJECTIVE: To evaluate the association between perioperative blood transfusion on
      the recurrence and survival of patient with advanced ovarian cancer. BACKGROUND:
      Cytoreductive surgery for ovarian cancer can be an extensive procedure often
      requiring allogeneic blood transfusions. Blood transfusions can have detrimental
      effects on immune function which can lead to a decrease in the organism ability
      to detect and destroy metastasis. METHODS: The study was a retrospective cohort
      investigation. Patients with advanced ovarian cancer (stage III) undergoing
      cytoreductive surgery were stratified by the need for perioperative blood
      transfusion. Allogeneic transfusions were non-leucodepleted. Primary outcome
      included time to recurrence and survival. Data were extracted from the
      gynaecology oncology database at Northwestern University. Times to event outcomes
      were evaluated by constructing Kaplan-Meyer curves and Cox regression. RESULTS:
      The charts of 136 subjects were evaluated. Seventy-six received blood
      transfusion. Median [95% confidence interval (CI)] time to recurrence for the non
      transfusion group was longer, i.e. 17 (6-27) months, compared to 11 (8-14) months
      for the transfused group (P = 0.03). Median (95% CI) survival following surgery
      was longer in the non-transfused group, i.e. 58 (43-73) months, compared to 36
      (28-44) months for the transfused group (P = 0.04). Cox regression showed that
      transfused subjects had shorter median times to recurrence and mortality after
      adjusting for age and tumour grade. CONCLUSIONS: There is an association between
      ovarian cancer recurrence and allogeneic perioperative blood transfusion in
      patients with advanced ovarian cancer undergoing cytoreductive surgery. These
      findings may have important implications in the perioperative management of those
      patients.

PMID- 22151921
TI  - Effectiveness of intramuscular corticosteroid injection versus placebo injection
      in patients with hip osteoarthritis: design of a randomized double-blinded
      controlled trial.
AB  - BACKGROUND: Recent international guidelines recommend intra-articular
      corticosteroid injections for patients with hip osteoarthritis who have moderate
      to severe pain and do not respond satisfactorily to oral analgesic/anti
      inflammatory agents. Of the five available randomized controlled trials, four
      showed positive effects with respect to pain reduction. However, intra-articular
      injection in the hip is complex because the joint is adjacent to important
      neurovascular structures and cannot be palpated. Therefore fluoroscopic or
      ultrasound guidance is needed.The systemic effect of corticosteroids has been
      studied in patients with impingement shoulder pain. Gluteal corticosteroid
      injection was almost as effective as ultrasound-guided subacromial corticosteroid
      injection. Such a clinically relevant effect of a systemic corticosteroid
      injection offers a less complex alternative for treatment of patients with hip
      osteoarthritis not responsive to oral pain medication. METHODS/DESIGN: This is a
      double-blinded, randomized controlled trial. A total of 135 patients (aged > 40
      years) with hip osteoarthritis and persistent pain despite oral analgesics
      visiting a general practitioner or orthopaedic surgeon will be included. They
      will be randomized to a gluteal intramuscular corticosteroid injection or a
      gluteal intramuscular placebo (saline) injection. The randomization will be
      stratified for setting (general practitioner and outpatient clinics of department
      of orthopaedics). Treatment effect will be evaluated by questionnaires at 2, 4,
      6, and 12 weeks follow-up and a physical examination at 12 weeks. Primary outcome
      is severity of hip pain reported by the patients at 2-week follow-up. Statistical
      analyses will be based on the intention-to-treat principle. DISCUSSION: This
      study will evaluate the effectiveness of an intramuscular corticosteroid
      injection on pain in patients with hip osteoarthritis. Patient recruitment has
      started. TRIAL REGISTRATION: This trial is registered in the Dutch Trial
      Registry: number NTR2966.

PMID- 22151922
TI  - Type 1 autoimmune pancreatitis.
AB  - Before the concept of autoimmune pancreatitis (AIP) was established, this form of
      pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or
      non-alcoholic duct destructive chronic pancreatitis based on unique histological
      features. With the discovery in 2001 that serum IgG4 concentrations are
      specifically elevated in AIP patients, this emerging entity has been more widely
      accepted. Classical cases of AIP are now called type 1 as another distinct
      subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of
      chronic pancreatitis cases, predominantly affects adult males. Patients usually
      present with obstructive jaundice due to enlargement of the pancreatic head or
      thickening of the lower bile duct wall. Pancreatic cancer is the leading
      differential diagnosis for which serological, imaging, and histological
      examinations need to be considered. Serologically, an elevated level of IgG4 is
      the most sensitive and specific finding. Imaging features include irregular
      narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a
      peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast
      enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic
      infiltration containing many IgG4+ plasma cells, storiform fibrosis, and
      obliterative phlebitis. A dramatic response to steroid therapy is another
      characteristic, and serological or radiological effects are normally identified
      within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic
      manifestation of systemic IgG4-related disease based on the fact that synchronous
      or metachronous lesions can develop in multiple organs (e.g. bile duct,
      salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those
      lesions are histologically identical irrespective of the organ of origin. Several
      potential autoantigens have been identified so far. A Th2-dominant immune
      reaction and the activation of regulatory T-cells are assumed to be involved in
      the underlying immune reaction. IgG4 antibodies have two unique biological
      functions, Fab-arm exchange and a rheumatoid factor-like activity, both of which
      may play immune-defensive roles. However, the exact role of IgG4 in this disease
      still remains to be clarified. It seems important to recognize this unique entity
      given that the disease is treatable with steroids.

PMID- 22151923
TI  - Isolation of bluetongue virus serotype 1 from Culicoides vector captured in
      livestock farms and sequence analysis of the viral genome segment-2.
AB  - Bluetongue virus serotype-1 (BTV-1) was isolated from Culicoides oxystoma vectors
      captured on livestock farms in two places of Gujarat, India. The viruses were
      isolated on BHK-21 cells, which produced characteristic BTV-related cytopathic
      effects between 24 and 48 h post-infection. Virus antigen was demonstrated in
      infected cells at different passage by a BTV-specific sandwich ELISA. Further,
      polyacrylamide gel electrophoresis and silver staining of viral genomic RNA
      revealed ten double-stranded RNA segments characteristic of BTV. Serotype of the
      isolates was identified by virus neutralization and PCR coupled with sequencing.
      The isolates were designated as SKN-7 and SKN-8 and their genome segment-2 (VP2)
      were sequenced. Phylogenetic analyses revealed very close relationship between
      them although they are not identical. SKN-8 showed closer relationship with a
      recently isolated BTV-1 from goat. Bluetongue virus was earlier isolated from
      Culicoides in adjacent state more than 20 years ago, although the serotype of the
      virus was not determined.

PMID- 22151924
TI  - Abatacept with methotrexate versus other biologic agents in treatment of patients
      with active rheumatoid arthritis despite methotrexate: a network meta-analysis.
AB  - INTRODUCTION: The goal of this study was to compare the efficacy in terms of
      Health Assessment Questionnaire change from baseline (HAQ CFB), 50% improvement
      in American College of Rheumatology criterion (ACR-50) and Disease Activity Score
      in 28 joints (DAS28) defined remission (< 2.6) between abatacept and other
      biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with
      rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX-IR).
      METHODS: A systematic literature review identified controlled trials
      investigating the efficacy of abatacept (three studies), etanercept (two
      studies), infliximab (two), adalimumab (two), certolizumab pegol (two) ritixumab
      (three), and tocilizumab (two) in MTX-IR patients with RA. The clinical trials
      included in this analysis were similar with respect to trial design, baseline
      patient characteristics and background therapy (MTX). The key clinical endpoints
      of interest were HAQ CFB, ACR-50 and DAS28 < 2.6 measured at 24 and 52 weeks. The
      results were analysed using network meta-analysis methods that enabled
      calculation of an estimate for expected relative effect of comparative
      treatments. Analysis results were expressed as the difference in HAQ CFB score
      and odds ratio (OR) of achieving an ACR-50 and DAS28 response and associated 95%
      credible intervals (CrI). RESULTS: The analysis of HAQ CFB at 24 weeks and 52
      weeks showed that abatacept in combination with MTX is expected to be more
      efficacious than MTX monotherapy and is expected to show a comparable efficacy
      relative to other biologic DMARDs in combination with MTX. Further, abatacept
      showed comparable ACR-50 and DAS28 < 2.6 response rates with other biologic
      DMARDs at 24 and 52 weeks, except for ACR-50 compared to certolizumab pegol at 52
      weeks and for DAS28 < 2.6 compared to tocilizumab at 24 weeks. Sensitivity
      analyses confirmed the robustness of the findings. CONCLUSIONS: Abatacept in
      combination with MTX is expected to result in a comparable change from baseline
      in HAQ score and comparable ACR-50 and DAS28 < 2.6 response rates in MTX-IR
      patients compared to other approved biologic agents.

PMID- 22151925
TI  - Neonatal scrotal wall necrotizing fasciitis (Fournier gangrene): a case report.
AB  - INTRODUCTION: Necrotizing fasciitis in neonates is rare and is associated with
      almost 50% mortality. Although more than 80 cases of neonates (under one month of
      age) with necrotizing fasciitis have been reported in the literature, only six of
      them are identified as originating in the scrotum. CASE PRESENTATION: We report
      the case of a four-week-old, full-term, otherwise-healthy Caucasian baby boy who
      presented with an ulcerating lesion of his scrotal wall. His scrotum was explored
      because of a provisional diagnosis of missed torsion of the testis. He was found
      to have necrotizing fasciitis of the scrotum. We were able to preserve the testis
      and excise the necrotic tissue, and with intravenous antibiotics there was a
      successful outcome. CONCLUSIONS: Fournier gangrene is rarely considered as part
      of the differential diagnosis in the clinical management of the acute scrotum.
      However, all doctors who care for small babies must be aware of this serious
      condition and, if it is suspected, should not hesitate in referring the babies to
      a specialist pediatric surgical center immediately.

PMID- 22151926
TI  - Cumulative exposure to gamma interferon-dependent chemokines CXCL9 and CXCL10
      correlates with worse outcome after lung transplant.
AB  - Outcomes following lung transplant are suboptimal owing to chronic allograft
      failure termed bronchiolitis obliterans syndrome (BOS). Prior work in both mice
      and humans has shown that interferon gamma (IFNG)-induced chemokines, including
      CXCL9 and CXCL10, are elevated in patients with established BOS. We hypothesized
      that patients who ultimately developed BOS would have elevations in these
      chemokines before losing lung function. We utilized a high throughput multiplex
      enzyme-linked immunosorbent assay (ELISA) to measure biomarkers in
      bronchoalveolar lavage fluid (BALF). We modeled cumulative exposure to seven
      biomarkers (CXCL9, CXCL10, RANTES, IL1-RA, IL-17, MCP1 and IL-13) by calculating
      the 1-year area under the curve (AUC) for each biomarker in the BALF of 40 lung
      transplant patients who had at least four samples obtained in the first year
      posttransplant. Cumulative elevations in CXCL9 and CXCL10 were associated with a
      significant risk of subsequent graft failure after transplant (HR 9.37 and 5.52,
      respectively; p < 0.01 for both). Further these chemokines were also elevated in
      patients before the onset of BOS. CXCL9 and CXCL10 elevations were seen between 3
      and 9 months before graft failure. Our data show that persistent presence of
      CXCL9 and CXCL10 portents worsening lung allograft function; measuring these IFNG
      induced chemokines might prospectively identify patients at risk for BOS.

PMID- 22151927
TI  - Ultrafast hole carrier relaxation dynamics in p-type CuO nanowires.
AB  - Ultrafast hole carrier relaxation dynamics in CuO nanowires have been
      investigated using transient absorption spectroscopy. Following femtosecond pulse
      excitation in a non-collinear pump-probe configuration, a combination of non
      degenerate transmission and reflection measurements reveal initial ultrafast
      state filling dynamics independent of the probing photon energy. This behavior is
      attributed to the occupation of states by photo-generated carriers in the
      intrinsic hole region of the p-type CuO nanowires located near the top of the
      valence band. Intensity measurements indicate an upper fluence threshold of 40
      MUJ/cm2 where carrier relaxation is mainly governed by the hole dynamics. The
      fast relaxation of the photo-generated carriers was determined to follow a double
      exponential decay with time constants of 0.4 ps and 2.1 ps. Furthermore, time
      correlated single photon counting measurements provide evidence of three
      exponential relaxation channels on the nanosecond timescale.

PMID- 22151928
TI  - Profile of gay men in Mexico City: results of a survey of meeting sites.
AB  - OBJECTIVE: To describe the distribution, size and characteristics of formal and
      non-formal meeting places for gay men in Mexico City, the general characteristics
      of this population, and the factors influencing HIV status and sexual behaviour
      among gay men. METHODS: Meeting sites for gay men in Mexico City were mapped, and
      the results were used as a sampling frame for an individual-level survey. For the
      survey, a random sample of sites was selected using a selection probability
      proportional to size, with the aim of interviewing approximately 3000 gay men.
      Multivariate logistic models were constructed to analyse the correlations between
      the population profile, and characteristics and behaviours related to HIV status.
      RESULTS: Mapping produced an estimated population attending these meeting places
      in Mexico City of about 6000-14 000 gay men, who were mostly young and
      economically active individuals with higher educational and socioeconomic levels
      than the average levels of the population as a whole. Approximately 67% of these
      men reported being tested for HIV at least once, and 30% of the men reported
      being HIV-positive. DISCUSSION: Participants' profile depicted the gay population
      in Mexico City as a highly educated community with a relatively high
      socioeconomic level. Despite their exposure to prevention efforts, members of
      this community reported unsafe behaviours consistent with the high prevalence of
      self-reported HIV infection.

PMID- 22151929
TI  - The Protein-Protein Interaction tasks of BioCreative III: classification/ranking
      of articles and linking bio-ontology concepts to full text.
AB  - BACKGROUND: Determining usefulness of biomedical text mining systems requires
      realistic task definition and data selection criteria without artificial
      constraints, measuring performance aspects that go beyond traditional metrics.
      The BioCreative III Protein-Protein Interaction (PPI) tasks were motivated by
      such considerations, trying to address aspects including how the end user would
      oversee the generated output, for instance by providing ranked results, textual
      evidence for human interpretation or measuring time savings by using automated
      systems. Detecting articles describing complex biological events like PPIs was
      addressed in the Article Classification Task (ACT), where participants were asked
      to implement tools for detecting PPI-describing abstracts. Therefore the BCIII
      ACT corpus was provided, which includes a training, development and test set of
      over 12,000 PPI relevant and non-relevant PubMed abstracts labeled manually by
      domain experts and recording also the human classification times. The Interaction
      Method Task (IMT) went beyond abstracts and required mining for associations
      between more than 3,500 full text articles and interaction detection method
      ontology concepts that had been applied to detect the PPIs reported in them.
      RESULTS: A total of 11 teams participated in at least one of the two PPI tasks
      (10 in ACT and 8 in the IMT) and a total of 62 persons were involved either as
      participants or in preparing data sets/evaluating these tasks. Per task, each
      team was allowed to submit five runs offline and another five online via the
      BioCreative Meta-Server. From the 52 runs submitted for the ACT, the highest
      Matthew's Correlation Coefficient (MCC) score measured was 0.55 at an accuracy of
      89% and the best AUC iP/R was 68%. Most ACT teams explored machine learning
      methods, some of them also used lexical resources like MeSH terms, PSI-MI
      concepts or particular lists of verbs and nouns, some integrated NER approaches.
      For the IMT, a total of 42 runs were evaluated by comparing systems against
      manually generated annotations done by curators from the BioGRID and MINT
      databases. The highest AUC iP/R achieved by any run was 53%, the best MCC score
      0.55. In case of competitive systems with an acceptable recall (above 35%) the
      macro-averaged precision ranged between 50% and 80%, with a maximum F-Score of
      55%. CONCLUSIONS: The results of the ACT task of BioCreative III indicate that
      classification of large unbalanced article collections reflecting the real class
      imbalance is still challenging. Nevertheless, text-mining tools that report
      ranked lists of relevant articles for manual selection can potentially reduce the
      time needed to identify half of the relevant articles to less than 1/4 of the
      time when compared to unranked results. Detecting associations between full text
      articles and interaction detection method PSI-MI terms (IMT) is more difficult
      than might be anticipated. This is due to the variability of method term
      mentions, errors resulting from pre-processing of articles provided as PDF files,
      and the heterogeneity and different granularity of method term concepts
      encountered in the ontology. However, combining the sophisticated techniques
      developed by the participants with supporting evidence strings derived from the
      articles for human interpretation could result in practical modules for
      biological annotation workflows.

PMID- 22151931
TI  - Reinvigorating cosmetic dermatology with the nanoparticle revolution.

PMID- 22151930
TI  - Interaction between Mycobacterium tuberculosis, Mycobacterium bovis,
      Mycobacterium avium subspecies paratuberculosis with the enteric glia and
      microglial cells.
AB  - BACKGROUND: We investigated the interaction of Mycobacterium avium subspecies
      paratuberculosis, M. bovis and M. tuberculosis and different glial cells (enteric
      glial and microglial cells) in order to evaluate the infecting ability of these
      microorganisms and the effects produced on these cells, such as the evaluation of
      cytokines expression. RESULTS: Our experiments demonstrated the adhesion of M.
      paratuberculosis to the enteroglial cells and the induction of IL-1A and IL-6
      expression; M. tuberculosis and M. bovis showed a good adhesive capability to the
      enteric cell line with the expression of the following cytokines: IL-1A and IL
      1B, TNF-alpha, G-CSF and GM-CSF; M. bovis induced the expression of IL-6 too.The
      experiment performed with the microglial cells confirmed the results obtained
      with the enteroglial cells after the infection with M. tuberculosis and M. bovis,
      whereas M. paratuberculosis stimulated the production of IL-1A and IL-1B.
      CONCLUSION: Enteroglial and microglial cells, could be the target of pathogenic
      mycobacteria and, even if present in different locations (Enteric Nervous System
      and Central Nervous System), show to have similar mechanism of immunomodulation.

PMID- 22151932
TI  - A randomized and placebo-controlled study to compare the skin-lightening efficacy
      and safety of lignin peroxidase cream vs. 2% hydroquinone cream.
AB  - BACKGROUND:   Historically, the most effective treatments for skin lightening
      have contained hydroquinone. However, there is a need for an effective
      alternative. AIMS:   The purpose of this study was to evaluate the skin
      lightening efficacy and safety of lignin peroxidase (LIP) creams using a regimen
      of both day and night products compared with twice-daily application of 2%
      hydroquinone cream and placebo in Asian women. PATIENTS/METHODS:   This was a
      randomized, double-blind, placebo-controlled, split-face, single-center study of
      51 patients. Patients were randomized to receive day and night LIP cream on one
      randomly selected side of their face and either 2% hydroquinone cream or placebo
      on the other. RESULTS:   A statistically significant change from baseline in the
      melanin index was observed in LIP-treated skin, with a mean reduction of 7.6% (P
      < 0.001) on Day 31. Conversely, hydroquinone and placebo did not provide a
      statistically significant lightening effect when instrumentally measured.
      Dermatologist scoring demonstrated a significant improvement in overall fairness
      as early as 8 days after treatment initiation in the LIP-treated group, which was
      not observed in the other groups. Overall, patients preferred the LIP creams.
      CONCLUSIONS:   The application of day/night LIP cream provided a significantly
      more rapid and observable skin-lightening effect than hydroquinone 2% cream or
      placebo.

PMID- 22151933
TI  - Topical vesicular formulations of Curcuma longa extract on recuperating the
      ultraviolet radiation-damaged skin.
AB  - BACKGROUND:   Ultraviolet radiations generate reactive oxygen species, leading to
      adverse effects on skin properties. Botanical extracts are multifunctional in
      nature having various properties like photoprotection, anti-aging, moisturizing,
      antioxidant, astringent, anti-irritant, and antimicrobial activity. AIMS:   The
      aim of this study was to formulate creams having Curcuma longa extract loaded
      novel vesicular systems (liposomes, ethosomes, and transfersomes) and study their
      photoprotective effect by assessment of skin hydration (Cutometer) and sebum
      content (Sebumeter). METHODS:   The alcoholic C. longa extract loaded liposomes,
      ethosomes, and transfersomes having 0.5-2.0% w/w extract were prepared, evaluated
      for size, entrapment efficiency, and incorporated into the cream. Their long-term
      interaction with skin (6 weeks) was compared in terms of their effects on skin
      hydration and sebum content. RESULTS:   Vesicular size obtained was in the range
      167.3 +/- 3.0 to 262.4 +/- 2.4 nm with low polydispersity index (0.2-0.3) and
      high entrapment efficiency. The efficacy was in the order C. longa extract loaded
      transfersomal creams > C. longa extract loaded ethosomal creams > C. longa
      extract loaded liposomal creams > C. longa extract loaded creams > Empty
      transfersome loaded cream > Empty ethosome loaded cream > Empty liposome loaded
      cream > Base cream. CONCLUSIONS:   The photoprotective properties of the
      constituents of C. longa extract and hydrant, moisturizing lipid components of
      nano vesicles with better skin penetration resulted in improvement in skin
      properties like skin hydration and sebum content. The herbal extract loaded nano
      vesicles incorporated in cream could be used as photoprotective formulations.

PMID- 22151934
TI  - A randomized controlled study to evaluate the depigmenting activity of L-ascorbic
      acid plus phytic acid-serum vs. placebo on solar lentigines.
AB  - BACKGROUND: Solar lentigines (SL) are benign signs of sun damage that many people
      find distressing. AIM: To assess the efficacy and safety of L-ascorbic acid 10% +
      phytic acid 2% for treating SL. PATIENTS/METHODS: A double-blind, vehicle
      controlled trial in 30 healthy subjects with >=2 SL. Subjects were randomly
      assigned to apply product to one side of the body and vehicle to the other twice
      daily for 3 months with follow-up of 2 months. RESULTS:   The pigmentation index
      for product-treated SL was reduced (maximum reduction 1.3 at 3 months [M3]),
      while that for vehicle-treated lesions remained stable. These differences were
      statistically significant for M1-M4 (P <= 0.003). Dermoscopy detected significant
      intergroup differences in pigmentation at M5 (P=0.011). Colorimetry results
      indicated a statistically significant improvement in brightness (L*) between
      study drug and vehicle at M5. Fifteen subjects experienced 23 adverse events; six
      (mostly halo depigmentation) were judged possibly related to the study drug.
      There were six instances of mild-to-moderate intolerance in the study drug group
      and five in the vehicle-treated group. CONCLUSIONS: Study treatment was
      significantly more efficacious than vehicle in many respects and was well
      tolerated. Future, larger studies are needed to confirm these results and to
      compare the product with gold standard treatments.

PMID- 22151935
TI  - Dermal penetration of creatine from a face-care formulation containing creatine,
      guarana and glycerol is linked to effective antiwrinkle and antisagging efficacy
      in male subjects.
AB  - BACKGROUND:   The dermal extracellular matrix provides stability and structure to
      the skin. With increasing age, however, its major component collagen is subject
      to degeneration, resulting in a gradual decline in skin elasticity and
      progression of wrinkle formation. Previous studies suggest that the reduction in
      cellular energy contributes to the diminished synthesis of cutaneous collagen
      during aging. AIMS:   To investigate the potential of topically applied creatine
      to improve the clinical signs of skin aging by stimulating dermal collagen
      synthesis in vitro and in vivo. PATIENTS/METHODS:   Penetration experiments were
      performed with a pig skin ex vivo model. Effects of creatine on dermal collagen
      gene expression and procollagen synthesis were studied in vitro using cultured
      fibroblast-populated collagen gels. In a single-center, controlled study, 43 male
      Caucasians applied a face-care formulation containing creatine, guarana extract,
      and glycerol to determine its influence on facial topometric features. RESULTS:  
      Cultured human dermal fibroblasts supplemented with creatine displayed a
      stimulation of collagen synthesis relative to untreated control cells both on the
      gene expression and at the protein level. In skin penetration experiments,
      topically applied creatine rapidly reached the dermis. In addition, topical in
      vivo application of a creatine-containing formulation for 6 weeks significantly
      reduced the sagging cheek intensity in the jowl area as compared to baseline.
      This result was confirmed by clinical live scoring, which also demonstrated a
      significant reduction in crow's feet wrinkles and wrinkles under the eyes.
      CONCLUSIONS:   In summary, creatine represents a beneficial active ingredient for
      topical use in the prevention and treatment of human skin aging.

PMID- 22151936
TI  - Comparative study of therapeutic effects of 20% azelaic acid and hydroquinone 4%
      cream in the treatment of melasma.
AB  - BACKGROUND:   Melasma is an irregular brown or grayish-brown symmetric facial
      hypermelanosis, often affecting women, especially those living in areas with
      intense ultraviolet radiation. OBJECTIVE:   Comparison of therapeutic effects of
      20% azelaic acid and 4% hydroquinone cream in the treatment of melasma. METHODS: 
      Twenty-nine women with melasma were recruited. Fifteen patients were treated
      with 4% hydroquinone cream and 14 patients were treated with azelaic acid cream
      for 2 months. The cream was applied twice daily. A broad-spectrum sunscreen was
      used concomitantly by both groups. The Melasma Area Severity Index (MASI) scores
      were determined prior to treatment and at each follow-up. RESULTS:   The mean
      MASI score before treatment was 7.2 +/- 3.2 in the hydroquinone group and 7.6 +/-
      3.5 in the azelaic acid group, with no significant difference between them (t
      test, CI 95% = -2.9 to 2.2). One month after treatment, the mean MASI score
      reached 6.7 +/- 3.4 with hydroquinone and 6.3 +/- 3.4 with azelaic acid with no
      significant difference between them (t-test, CI 95% = -2.2 to 3). After 2 months'
      treatment, the MASI score was 6.2 +/- 3.6 with hydroquinone and 3.8 +/- 2.8 with
      azelaic acid, a significant statistical difference (t-test, CI 95% = 0.03-4.9).
      CONCLUSIONS:   In conclusion, this study suggests that 20% azelaic acid cream
      applied twice daily may be more effective than hydroquinone 4% in reducing mild
      melasma. However, because this was an open trial, it is suggested that further
      studies involving large groups of patients be conducted to achieve a more
      conclusive result.

PMID- 22151937
TI  - Dynamics of skin barrier repair following preconditioning by a biotechnology
      driven extract from samphire (Crithmum maritimum) stem cells.
AB  - BACKGROUND:   With aging, the barrier repair kinetics following any weakening of
      the epidermal permeability barrier function is commonly slowed down. OBJECTIVE:  
      To assess the recovery rate of the epidermal permeability barrier function
      following controlled stripping and applications of samphire and control
      formulations. METHOD:   In 12 healthy subjects older than 50 years, controlled
      stratum corneum (SC) strippings were used to increase the transepidermal water
      loss (TEWL) just above 15 g/m(2) /h. This procedure followed a 14-day skin
      preconditioning by daily applications of formulations enriched or not with a
      samphire (Crithmum maritimum) biomass. An untreated skin site served as control.
      The epidermal permeability repair kinetics was assessed for 14 days by daily
      measurements of both TEWL and the colorimetric value a*. RESULTS:   A rapid (96
      h) recovery to lower TEWL values was obtained at each of the samphire
      preconditioned sites (0.1% serum, 0.05% cream, the serum-cream association, and
      0.5% silicone oil). This process was significantly (P < 0.001) faster than that
      on both the placebo-preconditioned (silicone oil) and the untreated sites. No
      adverse inflammatory and sensory reactions were recorded. At the sites
      preconditioned by samphire formulations, the SC moisture (capacitance) was higher
      at completion of the study compared to inclusion. CONCLUSIONS:   The present
      experimental pilot study brings some clues supporting a beneficial boosting
      effect of samphire cell biomass on the kinetics of epidermal permeability barrier
      repair.

PMID- 22151938
TI  - Fractional CO2 laser for the treatment of acne scars.
AB  - BACKGROUND:   Numerous reports have been published on skin rejuvenation by the so
      called fractional laser device that delivers a laser beam in a dot form over a
      grid pattern. AIMS:   In this study, we characterized the effects of a fractional
      CO(2) laser on atrophic acne scars at the clinical and ultrastructural levels.
      METHODS:   Seven healthy adult Japanese volunteers (aged 32-46 years, mean 37.6,
      five men and two women of Fitzpatrick skin type III) were recruited for this
      study. A fractional CO(2) laser device, SmartXide DOT (DEKA, Florence, Italy),
      was used with irradiation parameters set as follows: output power 10 W, pulse
      width 600 MUs, dot spacing 800 MUm, and stack 2 (irradiation output power 0.91
      J/cm(2) ). A clinical examination and punch biopsy of each subject was performed
      before and just after the irradiation, and also at week 3 after three irradiation
      sessions. The biopsy specimens were stained with toluidine blue and were examined
      ultrastructurally. RESULTS:   Clinical improvement of the atrophic acne scars was
      observed at week 3 after the third irradiation session in all cases compared with
      the condition before treatment. Histologically, outgrowths of many degenerated
      elastic fibers were observed as irregular rod-shaped masses in the superficial
      dermis prior to the treatment in the region of the acne scars. At week 3 after
      the third irradiation, the degenerated elastic fibers were no longer observed,
      and the elastic fibers were elaunin-like. CONCLUSIONS:   The fractional CO(2)
      laser is considered to be very effective for treating atrophic acne scars.

PMID- 22151939
TI  - Factors influencing postoperative hyperesthesia in hair restoration surgery.
AB  - BACKGROUND:   While esthetic outcomes in hair restoration surgery (HRS) have
      improved markedly since the advent of follicular unit transplantation (FUT),
      various undesirable sequelae persist. We investigated the technical and
      demographic variables that may contribute to the frequency of postoperative
      hyperesthesia. METHODS:   A multicenter retrospective chart review involving 552
      patients undergoing HRS from 1999 to 2009. RESULTS:   A total of 19 patients
      (3.4%) reported postoperative hyperesthesia in either the donor or recipient area
      of their scalp. Although many trends emerged, one variable significantly
      influenced the rate of this neurosensory symptom. While no patient who had all
      previous and current HRS sessions performed entirely within the same investigated
      surgical practice (n=42) experienced postoperative hyperesthesia, 14% of our
      patients who underwent prior HRS by a physician outside of the investigated
      surgical group (n=35) developed this complication (P=0.0404). The amount of
      intraoperative electrocautery to maintain hemostasis (P=0.0897), degree of
      tension upon donor wound closure (P=0.3044), and extent of donor wound edge
      undermining (P=0.4420) influenced the frequency of this sequela to a lesser
      degree. CONCLUSION:   These results suggest that physicians planning repair
      sessions on patients who have undergone prior HRS by a physician at a different
      surgical center should include the specific caveat of increased incidences of
      postoperative hyperesthesia in their preoperative consultation.

PMID- 22151940
TI  - Immediate vesicular eruption caused by topical 23% lidocaine 7% tetracaine
      ointment in a patient scheduled for laser therapy: a new adverse drug reaction.
AB  - Topical anesthetic agents have increased in number, formulations, and
      applications because of their efficacy and generally mild side effect profile. To
      date, there have been no reports of immediate vesicular eruption as a result of
      topical application of lidocaine or tetracaine. Two cases and a brief review of
      the literature are presented. We report the cases of two patients who presented
      for ablative laser therapy. Immediately after application of 23% lidocaine and 7%
      tetracaine mixed in an ointment base, the patients developed a diffuse eruption
      of vesicles and bullae on a well-demarcated erythematous base. The patients'
      lesions resolved after <1 week with gentle skin care. One patient developed
      macules of postinflammatory hyperpigmentation which faded over 2 months. One
      patient chose to cancel his laser therapy because of concerns over reproducing
      this adverse reaction, while the second will proceed using a different topical
      anesthetic agent. While topical anesthetic agents should generally be considered
      safe, they are not without risks. These cases illustrate a previously unreported
      adverse event. Clinicians should be vigilant for this and other adverse drug
      reactions to commonly used topical anesthetics like lidocaine and tetracaine.

PMID- 22151941
TI  - Twenty-four-month persistence of hyaluronic acid filler for an atrophic scar.
AB  - A 24-month follow up of a previously reported case of successful hyaluronic acid
      filler use in steroid atrophy is presented. The patient had persistence of the
      volume and appearance of her scar with sustained satisfaction 24 months after
      hyaluronic acid treatment, without the need for repeat injection. This case
      suggests expansion of the use of hyaluronic acid fillers to include scar atrophy,
      as persistence of a desired cosmetic appearance for 2 years is demonstrated.

PMID- 22151942
TI  - Side effects and complications of fractional 1550-nm erbium fiber laser treatment
      among Asians.
AB  - BACKGROUND:   Fractional erbium fiber laser is an effective treatment for facial
      wrinkles, acne scars, and dyspigmentation available worldwide. However, there are
      minimal data of adverse events and complications in Asians. OBJECTIVE:   To
      determine safety and adverse events associated with fractional erbium laser
      treatment in Asian patients. METHODS:   Retrospective data of 181 fractional 1550
      nm Ytterbium/Erbium fiber laser (Finescan(TM) ; TNC Medditron Co., Ltd.,
      Thailand) from 119 patients with skin phototype III-V at Ramathibodi Laser Center
      were reviewed. Patient demographics including gender, age, and dermatologic
      indications for treatment were assessed. Safety and adverse effects related to
      the treatment were identified. RESULTS:   Only six treatments (3.3%) developed
      complications. The most common adverse event was postinflammatory
      hyperpigmentation (2.2%), while acneiform eruption and desquamation were reported
      0.55%, equally. Although none of the patients received herpes prophylaxis, there
      were no herpes outbreaks. CONCLUSION:   Fractional erbium laser treatment in
      Asian skin is quite safe, and the side effects in this study were relatively low.
      Herpes prophylaxis may not be required.

PMID- 22151943
TI  - Combination of microneedling and glycolic acid peels for the treatment of acne
      scars in dark skin.
AB  - INTRODUCTION:   Acne scars can cause emotional and psychosocial disturbance to
      the patient. Various modalities have been used for the treatment of acne scars
      like punch excision, subcision, peels, microdermabrasion, unfractionated and
      fractioned lasers. The latest in the treatment armamentarium is microneedling.
      Acne scars commonly coexist with postinflammatory hyperpigmentation. A
      combination of microneedling and glycolic acid (GA) peels was found to give
      excellent results in the treatment of such scars. The aim was to study the
      efficacy of a combination of microneedling with glycolic peel for the treatment
      of acne scars in pigmented skin. METHOD:   Thirty patients in the age group of 20
      40 years with atrophic box type or rolling scars with postinflammatory
      hyperpigmentation were chosen for the study. Two groups were made. The first
      group comprised of 30 patients in whom only microneedling was performed once in 6
      weeks for five sessions. In the second group of 30 patients, a combination of
      microneedling and 35% GA peels was carried out. Patients from both groups were
      evaluated on the basis of Echelle d'Evaluation clinique des Cicatrices d'acne
      classification. RESULTS:   Based on the objective scoring and its statistical
      analysis, there was significant improvement in superficial and moderately deep
      scars (grade 1-3). There was also improvement in skin texture, reduction in
      postacne pigmentation in the second group. CONCLUSION:   Microneedling is a
      simple, inexpensive office procedure with no downtime. It is safe in Indian skin
      (skin types III-IV). The combined sequential treatment with GA peel caused a
      significant improvement in the acne scars without increasing morbidity.

PMID- 22151944
TI  - Diethylene glycol monoethyl ether: an emerging solvent in topical dermatology
      products.
AB  - BACKGROUND:   The solvent diethylene glycol monoethyl ether (DEGEE) is currently
      used in over 500 cosmetic products and has enabled the formulation of a topical
      5% dapsone gel for the treatment of acne. It is anticipated that this common
      cosmetic ingredient will be a component in numerous future prescription topical
      products approved for the US market. Dermatologists are already treating patients
      that apply products containing 5-40% of this solvent multiple times each day.
      AIMS:   To provide dermatologists a review of this solvent's safety and tolerance
      in addition to describing how it interacts with the stratum corneum, sebum, and
      resident microflora. METHODS:   To critically review technical and patent
      literature that provides insight into this novel solvent. RESULTS:   Diethylene
      glycol monoethyl ether when used in a 99.9+% pure pharmaceutical grade is safe
      and well tolerated. Up to half of the applied solvent crosses the skin's barrier
      and becomes systemic. For certain drug actives, this solvent provides for an
      intracutaneous depot. This solvent has not demonstrated any inherent
      antimicrobial properties but was found to be mildly inhibitory toward
      Propionibacterium acnes. CONCLUSIONS:   This safe, well-tolerated solvent is
      already used in many cosmetics and will become an ingredient in an increasing
      number of prescription products. Its ability to modify the skin delivery of
      actives it is formulated with (or formulation components that are applied just
      shortly before or after) make it important for dermatologists to have an
      understanding of this emerging solvent.

PMID- 22151945
TI  - New malignancies following cancer of the urinary bladder: analysis of German
      cancer registry data.
AB  - This analysis aimed at occurrence and distribution patterns of new malignancies
      following bladder cancer. Standardised incidence ratios (SIRs) were calculated
      for two German population-based cancer registries of North Rhine-Westphalia (NRW)
      and Saarland to access risks for subsequent primaries. An elevated risk for
      secondary cancer of any site but urothelium was observed in NRW men [SIR 1.35,
      95% confidence interval (CI) 1.22-1.49]. The corresponding risk in Saarland was
      not significantly elevated (SIR 1.06, 95% CI 0.97-1.15). In data of both
      registries excess risks were observed for cancer of the respiratory tract (SIR
      1.54, CI 1.23-1.89 in NRW men) and the prostate (SIR 1.91, 95% CI 1.61-2.24 in
      NRW; SIR 1.25, 95% CI 1.07-1.45 in Saarland). Common risk factors and incidental
      findings during follow-up care of bladder cancer patients might explain most of
      the observed patterns. In addition SIRs were throughout particular high for
      subsequent cancer of the renal pelvis and the ureter due to pathological
      characteristics of urothelial neoplasms.

PMID- 22151946
TI  - Enhanced expression of membrane proteins in E. coli with a P(BAD) promoter
      mutant: synergies with chaperone pathway engineering strategies.
AB  - BACKGROUND: Membrane proteins (MPs) populate 20-30% of genomes sequenced to date
      and hold potential as therapeutic targets as well as for practical applications
      in bionanotechnology. However, MP toxicity and low yields in normally robust
      expression hosts such as E. coli has curtailed progress in our understanding of
      their structure and function. RESULTS: Using the seven transmembrane segments H.
      turkmenica deltarhodopsin (HtdR) as a reporter, we isolated a spontaneous mutant
      in the arabinose-inducible P(BAD) promoter leading to improved cell growth and a
      twofold increase in the recovery of active HtdR at 37 degrees C. A single
      transversion in a conserved region of the cyclic AMP receptor protein binding
      site caused the phenotype by reducing htdR transcript levels by 65%. When the
      mutant promoter was used in conjunction with a host lacking the molecular
      chaperone Trigger Factor (Deltatig cells), toxicity was further suppressed and
      the amount of correctly folded HtdR was 4-fold that present in the membranes of
      control cells. More importantly, while improved growth barely compensated for the
      reduction in transcription rates when another polytopic membrane protein (N.
      pharonis sensory rhodopsin II) was expressed under control of the mutant promoter
      in wild type cells, a 4-fold increase in productivity could be achieved in a
      Deltatig host. CONCLUSIONS: Our system, which combines a downregulated version of
      the tightly repressed P(BAD) promoter with a TF-deficient host may prove a
      valuable alternative to T7-based expression for the production of membrane
      proteins that have so far remained elusive targets.

PMID- 22151947
TI  - Assessment of endothelial function by brachial artery flow mediated dilatation in
      microvascular disease.
AB  - BACKGROUND: Cardiac syndrome X is an important therapeutic and diagnostic
      challenge to physician. Study of Csx patients may help to understand the
      pathophysiology of coronary microcirculation and to gain an insight on the
      management of these group patients. METHODS: We measured the flow mediated
      dilation of the brachial artery both endothelium dependent and independent
      vasodilatation by high resolution ultrasound in 30 cardiac syndrome X patients
      and matched with 30 healthy control subjects. RESULTS: Significantly decreased
      flow mediated dilatation was observed in patients when compared to control
      (9.42+/-7.20 vs 21.11+/-9.16 p<0.01) but no significant difference was observed
      between groups in response to nitroglycerin (25.39+/-6.82 vs 28.87+/-8.69).
      Receiver operator characteristic analysis showed that value of <11.11 had
      sensitivity of 80%, specificity 86.67%, positive predictive value 76.66%,
      negative predictive value 83.33%. In total, 46% of subjects had endothelial
      dysfunction and of them, CSX subjects had higher prevalence (76% vs 16% p<0.01)
      than control subjects. Higher mean values of body mass index, systolic blood
      pressure and diastolic blood pressure was observed in subjects with FMD<11.11
      than >11.11(p<0.01). In logistic regression analysis, FMD was significantly
      associated with systolic blood pressure (Odds ratio 1.122 95% CI 1.053-1.196
      p<0.01) and body mass index (Odds 1.248 95%CI 0.995-1.56 p<0.05). CONCLUSIONS:
      The study suggests impairment of endothelial function in cardiac syndrome X
      patients. Increased Systolic blood pressure and body mass index may increase the
      risk of impairment of endothelial function in this group of patients.

PMID- 22151948
TI  - Approximating the double-cut-and-join distance between unsigned genomes.
AB  - In this paper we study the problem of sorting unsigned genomes by double-cut-and
      join operations, where genomes allow a mix of linear and circular chromosomes to
      be present. First, we formulate an equivalent optimization problem, called
      maximum cycle/path decomposition, which is aimed at finding a largest collection
      of edge-disjoint cycles/AA-paths/AB-paths in a breakpoint graph. Then, we show
      that the problem of finding a largest collection of edge-disjoint cycles/AA
      paths/AB-paths of length no more than l can be reduced to the well-known degree
      bounded k-set packing problem with k = 2l. Finally, a polynomial-time
      approximation algorithm for the problem of sorting unsigned genomes by double-cut
      and-join operations is devised, which achieves the approximation ratio 13/9 +
      epsilon ~ 1.4444 + epsilon, for any positive epsilon. For the restricted
      variation where each genome contains only one linear chromosome, the
      approximation ratio can be further improved to 69/49 + epsilon ~ 1.4082 +
      epsilon.

PMID- 22151949
TI  - The 'frozen state' of drug-resistant tuberculosis: notes from the field in
      Abkhazia.

PMID- 22151950
TI  - Menstrual cycle variation of retroperitoneal lymphangioleiomyomas in
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare disease affecting women, classically
      involving the lungs. However, extrapulmonary manifestations also occur, including
      renal angiomyolipomas, retroperitoneal lymphangioleiomyomas and extrathoracic
      lymphadenopathy. The lung disease is hormone-responsive, but no information
      exists regarding sex hormone responsiveness of abdominal LAM. Here, we report two
      women with LAM whose abdominal lymphangioleiomyomas increased in size with
      hormonal changes of the menstrual cycle. This is the first description of
      abdominal lymphangioleiomyomas exhibiting hormone responsiveness in LAM. We
      describe these cases and summarize the literature on abdominal LAM. Menstrual
      cycle variation should be taken into account when assessing response to therapy,
      both clinically and in research studies.

PMID- 22151951
TI  - History of cardiac pacing in New Zealand: the early years.
AB  - This paper documents the development of cardiac pacing in New Zealand in the
      early years following the first implant in 1961. This period covered the time of
      the early development and evolution of cardiac pacemakers. Pacemaker
      implantations were infrequent and high risk in desperately ill patients. Whilst
      lifesaving the pacemakers had poor longevity, were unreliable and required
      frequent revisions.

PMID- 22151952
TI  - Where have all the blue flowers gone: pollinator responses and selection on
      flower colour in New Zealand Wahlenbergia albomarginata.
AB  - Although pollinators are thought to select on flower colour, few studies have
      experimentally decoupled effects of colour from correlated traits on pollinator
      visitation and pollen transfer. We combined selection analysis and phenotypic
      manipulations to measure the effect of petal colour on visitation and pollen
      export at two spatial scales in Wahlenbergia albomarginata. This species is
      representative of many New Zealand alpine herbs that have secondarily evolved
      white or pale flowers. The major pollinators, solitary bees, exerted phenotypic
      selection on flower size but not colour, quantified by bee vision. When presented
      with manipulated flowers, bees visited flowers painted blue to resemble a
      congener over white flowers in large, but not small, experimental arrays. Pollen
      export was higher for blue flowers in large arrays. Pollinator preference does
      not explain the pale colouration of W. albomarginata, as commonly hypothesized.
      Absence of bright blue could be driven instead by indirect selection of
      correlated characters.

PMID- 22151953
TI  - Breast cancer and sexuality: multi-modal treatment options.
AB  - The sexual consequences of breast cancer and its treatments are well known and
      previously reviewed. Alterations in body image, with or without breast
      reconstruction, changes in sexual self-esteem and self-efficacy, vulvovaginal
      atrophy as a result of chemotherapy and/or adjuvant hormone therapy, and loss of
      libido secondary to dyspareunia and body image issues are common in survivors of
      breast cancer. Medications that are prescribed for long-term use including those
      in the class of aromatase inhibitors can have far-reaching implications on
      quality of life by contributing to vulvar and vaginal atrophic changes. While
      this is an important issue, there are few widely accepted treatments that have
      been evaluated for efficacy and safety for these sexual challenges in the breast
      cancer population. However, progress is being made in finding new and innovative
      solutions for many of the sexual problems faced by breast cancer survivors and
      their partners. Many institutions are now compelled to address survivorship
      concerns and addressing sexuality and intimacy are paramount issues in
      survivorship care. In this article, we present the evidence for the multimodal
      approach to the management of sexuality concerns in the breast cancer survivor.
      Pharmacologic, nonpharmacologic, and psychosocial interventions will be reviewed.

PMID- 22151956
TI  - ExActa purinergic signalling.

PMID- 22151954
TI  - Appreciation and implementation of the Krachtvoer healthy diet promotion
      programme for 12- to 14- year-old students of prevocational schools.
AB  - BACKGROUND: Krachtvoer is a school-based healthy diet programme, developed in
      2001 and revised in 2007 to meet the needs of particular segments of the target
      population as well as a wider target group. The main aims of the present process
      evaluation of the revised programme were to examine student and teacher
      appreciation of the programme, completeness of and adherence to its
      implementation, and relations between appreciation and completeness of
      implementation. METHODS: Data were collected among 22 teachers and 1117 students
      of 13 schools, using student evaluation forms, teacher logbooks, telephone
      interviews, and classroom observations. RESULTS: Results indicate favourable
      levels of teacher and student appreciation for the programme in general and the
      revised elements. Girls, first-year students and students with more favourable
      dietary intakes particularly appreciated individual programme elements. Levels of
      completeness of implementation were high, but several teachers did not adhere to
      the intended implementation period. Some moderately strong relations were found
      between teacher appreciation and completeness of implementation scores.
      CONCLUSION: We conclude that the revisions have resulted in a programme that was
      appreciated well, also by the extended target group, and was implemented with a
      high degree of completeness. Teacher appreciation proved potentially important
      for completeness of implementation. We identified several aspects requiring
      improvement, indicating the importance of continued programme updates and
      repeated evaluation.

PMID- 22151958
TI  - Quantification and determination of spread mechanisms of bovine viral diarrhoea
      virus in blood and tissues from colostrum-deprived calves during an experimental
      acute infection induced by a non-cytopathic genotype 1 strain.
AB  - To detect and monitor the sequential changes in virus levels, a reverse
      transcription quantitative real-time polymerase chain reaction assay using a
      TaqMan probe was carried out on frozen blood and tissues samples collected from
      calves experimentally infected with a non-cytopathic Bovine viral diarrhoea virus
      (BVDV) genotype 1 strain. Blood samples were collected among days 1-14 post
      inoculation (p.i). On day 3 p.i, viral RNA was detected in blood samples from six
      of the eight inoculated animals. Viral RNA was detected in all remaining
      inoculated animals between 5 and 12 days p.i. The levels of viral RNA increased
      along the experiment, with a maximal peak between 6 and 9 days p.i. Analysis of
      virus load in tissues collected from calves euthanized on days 3, 6, 9 and 14 p.i
      displayed that BVDV was detected on day 3 p.i, being especially abundant in
      tonsils and ileocaecal valve, highlighting the role of tonsils as the main
      earliest viral replication sites as well as the principal source for virus spread
      to other lymphoid tissues and visceral organs. Coinciding with the highest
      viraemia levels, the highest viral loads were recorded at 9 days p.i. in tonsils,
      ileal lymph nodes, distal ileum and spleen, showing the main role of these
      secondary lymphoid organs in the pathogenic mechanisms of BVDV. However, virus
      levels in the liver and lung increased only towards the end of the infection.
      This fact could influence in the appearance of bovine respiratory diseases
      because of the capacity of BVDV for enhancing susceptibility to secondary
      infections.

PMID- 22151959
TI  - The small heat shock proteins from Acidithiobacillus ferrooxidans: gene
      expression, phylogenetic analysis, and structural modeling.
AB  - BACKGROUND: Acidithiobacillus ferrooxidans is an acidophilic,
      chemolithoautotrophic bacterium that has been successfully used in metal
      bioleaching. In this study, an analysis of the A. ferrooxidans ATCC 23270 genome
      revealed the presence of three sHSP genes, Afe_1009, Afe_1437 and Afe_2172, that
      encode proteins from the HSP20 family, a class of intracellular multimers that is
      especially important in extremophile microorganisms. RESULTS: The expression of
      the sHSP genes was investigated in A. ferrooxidans cells submitted to a heat
      shock at 40 degrees C for 15, 30 and 60 minutes. After 60 minutes, the gene on
      locus Afe_1437 was about 20-fold more highly expressed than the gene on locus
      Afe_2172. Bioinformatic and phylogenetic analyses showed that the sHSPs from A.
      ferrooxidans are possible non-paralogous proteins, and are regulated by the
      sigma32 factor, a common transcription factor of heat shock proteins. Structural
      studies using homology molecular modeling indicated that the proteins encoded by
      Afe_1009 and Afe_1437 have a conserved alpha-crystallin domain and share similar
      structural features with the sHSP from Methanococcus jannaschii, suggesting that
      their biological assembly involves 24 molecules and resembles a hollow spherical
      shell. CONCLUSION: We conclude that the sHSPs encoded by the Afe_1437 and
      Afe_1009 genes are more likely to act as molecular chaperones in the A.
      ferrooxidans heat shock response. In addition, the three sHSPs from A.
      ferrooxidans are not recent paralogs, and the Afe_1437 and Afe_1009 genes could
      be inherited horizontally by A. ferrooxidans.

PMID- 22151960
TI  - Predictors and outcome of surgical repair of obstetric fistula at a regional
      referral hospital, Mbarara, western Uganda.
AB  - BACKGROUND: Obstetric fistula although virtually eliminated in high income
      countries, still remains a prevalent and debilitating condition in many parts of
      the developing world. It occurs in areas where access to care at childbirth is
      limited, or of poor quality and where few hospitals offer the necessary
      corrective surgery. METHODS: This was a prospective observational study where all
      women who attended Mbarara Regional Referral Hospital in western Uganda with
      obstetric fistula during the study period were assessed pre-operatively for
      social demographics, fistula characteristics, classification and outcomes after
      surgery. Assessment for fistula closure and stress incontinence after surgery was
      done using a dye test before discharge RESULTS: Of the 77 women who were
      recruited in this study, 60 (77.9%) had successful closure of their fistulae.
      Unsuccessful fistula closure was significantly associated with large fistula size
      (Odds Ratio 6 95% Confidential interval 1.46-24.63), circumferential fistulae
      (Odds ratio 9.33 95% Confidential interval 2.23-39.12) and moderate to severe
      vaginal scarring (Odds ratio 12.24 95% Confidential interval 1.52-98.30). Vaginal
      scarring was the only factor independently associated with unsuccessful fistula
      repair (Odds ratio 10 95% confidential interval 1.12-100.57). Residual stress
      incontinence after successful fistula closure was associated with type IIb
      fistulae (Odds ratio 5.56 95% Confidential interval 1.34-23.02), circumferential
      fistulae (Odds ratio 10.5 95% Confidential interval 1.39-79.13) and previous
      unsuccessful fistula repair (Odds ratio 4.8 95% Confidential interval 1.27
      18.11). Independent predictors for residual stress incontinence after successful
      fistula closure were urethral involvement (Odds Ratio 4.024 95% Confidential
      interval 2.77-5.83) and previous unsuccessful fistula repair (Odds ratio 38.69
      95% Confidential interval 2.13-703.88). CONCLUSIONS: This study demonstrated that
      large fistula size, circumferential fistulae and marked vaginal scarring are
      predictors for unsuccessful fistula repair while predictors for residual stress
      incontinence after successful fistula closure were urethral involvement,
      circumferential fistulae and previous unsuccessful fistula repair.

PMID- 22151961
TI  - Testing for fertility stalls in demographic and health surveys.
AB  - This study compares two methods for testing fertility trends and fertility
      stalls using Demographic and Health Surveys data. The first method is based on
      linear regression and uses the equivalence of period and cohort estimates with
      the same cumulative fertility at age 40, the same number of births, and the same
      distribution of women by parity. The second method is based on logistic
      regression. It assumes that the age pattern of fertility is constant over short
      periods of time. Both methods were applied to fertility trends in several African
      countries (Ghana, Kenya, Madagascar, Nigeria, Rwanda, Senegal, Tanzania, and
      Zambia). The two methods were found to predict similar values of cumulative
      fertility, to produce consistent slopes, to document fertility trends the same
      way, and to characterize fertility stalls with similar statistical evidence. They
      can also be used to refute apparent fertility stalls obtained when comparing two
      point estimates from two successive surveys.

PMID- 22151962
TI  - Tumor-infiltrating lymphocytes predict response to anthracycline-based
      chemotherapy in estrogen receptor-negative breast cancer.
AB  - INTRODUCTION: Infiltration of breast tumors by tumor-infiltrating lymphocytes
      (TIL) has been associated with sensitivity to anthracycline-based chemotherapy.
      However, it is unclear whether this is true within the estrogen receptor-alpha
      (ER)-negative subset of breast tumors that frequently manifest high TIL levels.
      METHODS: The association of TIL with short-term and long-term clinical response
      to anthracycline-based therapy was assessed in two independent ER-negative breast
      cancer cohorts in which patients were categorized as TIL-high or TIL-low. We
      defined an eight-gene lymphocyte mRNA expression signature (including CD19, CD3D,
      CD48, GZMB, LCK, MS4A1, PRF1, and SELL) and used unsupervised hierarchical
      clustering to examine the association between TIL and short-term response to
      neoadjuvant chemotherapy in a previously published cohort of ER-negative tumors
      (n = 113). We also examined the association between TIL and long-term
      chemotherapeutic efficacy in a second cohort of ER-negative tumors (n = 255) with
      longer than 6 years of median follow-up by using tissue microarrays and
      immunohistochemistry (IHC) for detection of CD3, CD8, CD4, CD20, and TIA-1.
      RESULTS: In patients with ER-negative tumors treated with neoadjuvant
      anthracycline-based chemotherapy, pathologic complete responses (pCRs) were
      achieved by 23 (74%) of 31 TIL-high patients and 25 (31%) of 80 TIL-low patients
      (odds ratio (OR), 6.33; 95% confidence interval (CI), 2.49 to 16.08; P < 0.0001).
      Multivariate logistic regression with standard clinicopathologic features
      demonstrated that only tumor size (P = 0.037) and TIL status (P = 0.001) were
      independent predictors of anthracycline response. In the second cohort, adjuvant
      anthracycline-based therapy was associated with increased disease-free survival
      (DFS) only in patients with high levels of intraepithelial CD3+ TIL (P = 0.0023).
      In contrast, outcomes after CMF treatment (cyclophosphamide, methotrexate, and
      fluorouracil) showed no association with CD3 status. In both cohorts, cytotoxic T
      cells were the primary TIL subtype associated with anthracycline sensitivity.
      Finally, TIL significantly predicted anthracycline sensitivity for both the Her2
      positive and triple-negative tumor phenotypes. CONCLUSIONS: ER-negative breast
      cancers with high levels of TIL have heightened sensitivity to anthracycline
      based chemotherapy, as assessed by the immediate response to neoadjuvant therapy
      and long-term outcome following adjuvant therapy. Investigations of TIL-based
      predictive tests to identify patients likely to benefit from anthracycline-based
      treatments are warranted.

PMID- 22151963
TI  - Delineation of the clinical phenotype associated with non-mosaic type-2 NF1
      deletions: two case reports.
AB  - INTRODUCTION: Large deletions of the NF1 gene and its flanking regions are
      frequently associated with a severe clinical manifestation. Different types of
      gross NF1 deletion have been identified that are distinguishable both by their
      size and the number of genes included within the deleted regions. Type-1 NF1
      deletions encompass 1.4 Mb and include 14 genes, whereas the much less common
      type-2 NF1 deletions span 1.2 Mb and contain 13 genes. Genotype-phenotype
      correlations in patients with large NF1 deletions are likely to be influenced by
      the nature and number of the genes deleted in addition to the NF1 gene. Whereas
      the clinical phenotype associated with type-1 NF1 deletions has been well
      documented, the detailed clinical characterization of patients with non-mosaic
      type-2 NF1 deletions has not so far been reported. CASE PRESENTATION: In the
      present report we characterized two Caucasian European patients with non-mosaic
      (germline) type-2 NF1 deletions. Our first patient was a 13-year-old girl with
      dysmorphic facial features, mild developmental delay, large hands and feet,
      hyperflexibility of the joints, macrocephaly and T2 hyperintensities in the
      brain. A whole-body magnetic resonance imaging scan indicated two internal
      plexiform neurofibromas. Our second patient was an 18-year-old man who exhibited
      dysmorphic facial features, developmental delay, learning disability, large hands
      and feet, hyperflexibility of the joints, macrocephaly and a very high
      subcutaneous and internal tumor load as measured volumetrically on whole-body
      magnetic resonance imaging scans. At the age of 18 years, he developed a
      malignant peripheral nerve sheath tumor and died from secondary complications.
      Both our patients exhibited cardiovascular malformations. CONCLUSIONS: Our two
      patients with non-mosaic type-2 NF1 deletions exhibited clinical features that
      have been reported in individuals with germline type-1 NF1 deletions. Therefore,
      a severe disease manifestation is not confined to only patients with type-1 NF1
      deletions but may also occur in individuals with type-2 NF1 deletions. Our
      findings support the concept of an NF1 microdeletion syndrome with severe
      clinical manifestation that is caused by type-1 as well as type-2 NF1 deletions.

PMID- 22151965
TI  - Stagnation-point flow over a stretching/shrinking sheet in a nanofluid.
AB  - An analysis is carried out to study the steady two-dimensional stagnation-point
      flow of a nanofluid over a stretching/shrinking sheet in its own plane. The
      stretching/shrinking velocity and the ambient fluid velocity are assumed to vary
      linearly with the distance from the stagnation point. The similarity equations
      are solved numerically for three types of nanoparticles, namely copper, alumina,
      and titania in the water-based fluid with Prandtl number Pr = 6.2. The skin
      friction coefficient, Nusselt number, and the velocity and temperature profiles
      are presented graphically and discussed. Effects of the solid volume fraction phi
      on the fluid flow and heat transfer characteristics are thoroughly examined.
      Different from a stretching sheet, it is found that the solutions for a shrinking
      sheet are non-unique.

PMID- 22151964
TI  - Efficacy of vinblastine in central nervous system Langerhans cell histiocytosis:
      a nationwide retrospective study.
AB  - BACKGROUND: Vinblastine (VBL) is the standard treatment for systemic Langerhans
      cell histiocytosis (LCH), but little is known about its efficacy in central
      nervous system (CNS) mass lesions. METHODS: A retrospective chart review was
      conducted. Twenty patients from the French LCH Study Group register met the
      inclusion criteria. In brief, they had CNS mass lesions, had been treated with
      VBL, and were evaluable for radiologic response. RESULTS: The median age at
      diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m2 was given
      in a 6-week induction treatment, followed by a maintenance treatment. The median
      total duration was 12 months (range: 3-30). Eleven patients received steroids
      concomitantly. Fifteen patients achieved an objective response; five had a
      complete response (CR: 25%), ten had a partial response (PR: 50%), four had
      stable disease (SD: 20%) and one patient progressed (PD: 5%). Of interest, four
      out of the six patients who received VBL without concomitant steroids achieved an
      objective response. With a median follow-up of 6.8 years, the 5-year event-free
      and overall survival was 61% and 84%, respectively. VBL was well-tolerated and
      there were no patient withdrawals due to adverse events. CONCLUSION: VBL, with or
      without steroids, could potentially be a useful therapeutic option in LCH with
      CNS mass lesions, especially for those with inoperable lesions or multiple
      lesions. Prospective clinical trials are warranted for the evaluation of VBL in
      this indication.

PMID- 22151966
TI  - Translational research in lung transplantation: how do we get from mouse to
      human?

PMID- 22151967
TI  - Oral administration of interferon-alpha2b-transformed Bifidobacterium longum
      protects BALB/c mice against coxsackievirus B3-induced myocarditis.
AB  - Multiple reports have claimed that low-dose orally administered interferon (IFN)
      alpha is beneficial in the treatment of many infectious diseases and provides a
      viable alternative to high-dose intramuscular treatment. However, research is
      needed on how to express IFN stably in the gut. Bifidobacterium may be a suitable
      carrier for human gene expression and secretion in the intestinal tract for the
      treatment of gastrointestinal diseases. We reported previously that
      Bifidobacterium longum can be used as a novel oral delivery of IFN-alpha. IFN
      transformed B. longum can exert an immunostimulatory role in mice; however the
      answer to whether this recombinant B. longum can be used to treat virus infection
      still remains elusive. Here, we investigated the efficacy of IFN-transformed B.
      longum administered orally on coxsackie virus B3 (CVB3)-induced myocarditis in
      BALB/c mice. Our data indicated that oral administration of IFN-transformed B.
      longum for 2 weeks after virus infection reduced significantly the severity of
      virus-induced myocarditis, markedly down regulated virus titers in the heart, and
      induced a T helper 1 cell pattern in the spleen and heart compared with controls.
      Oral administration of the IFN-transformed B. longum, therefore, may play a
      potential role in the treatment of CVB3-induced myocarditis.

PMID- 22151968
TI  - BioCreative III interactive task: an overview.
AB  - BACKGROUND: The BioCreative challenge evaluation is a community-wide effort for
      evaluating text mining and information extraction systems applied to the
      biological domain. The biocurator community, as an active user of biomedical
      literature, provides a diverse and engaged end user group for text mining tools.
      Earlier BioCreative challenges involved many text mining teams in developing
      basic capabilities relevant to biological curation, but they did not address the
      issues of system usage, insertion into the workflow and adoption by curators.
      Thus in BioCreative III (BC-III), the InterActive Task (IAT) was introduced to
      address the utility and usability of text mining tools for real-life biocuration
      tasks. To support the aims of the IAT in BC-III, involvement of both developers
      and end users was solicited, and the development of a user interface to address
      the tasks interactively was requested. RESULTS: A User Advisory Group (UAG)
      actively participated in the IAT design and assessment. The task focused on gene
      normalization (identifying gene mentions in the article and linking these genes
      to standard database identifiers), gene ranking based on the overall importance
      of each gene mentioned in the article, and gene-oriented document retrieval
      (identifying full text papers relevant to a selected gene). Six systems
      participated and all processed and displayed the same set of articles. The
      articles were selected based on content known to be problematic for curation,
      such as ambiguity of gene names, coverage of multiple genes and species, or
      introduction of a new gene name. Members of the UAG curated three articles for
      training and assessment purposes, and each member was assigned a system to
      review. A questionnaire related to the interface usability and task performance
      (as measured by precision and recall) was answered after systems were used to
      curate articles. Although the limited number of articles analyzed and users
      involved in the IAT experiment precluded rigorous quantitative analysis of the
      results, a qualitative analysis provided valuable insight into some of the
      problems encountered by users when using the systems. The overall assessment
      indicates that the system usability features appealed to most users, but the
      system performance was suboptimal (mainly due to low accuracy in gene
      normalization). Some of the issues included failure of species identification and
      gene name ambiguity in the gene normalization task leading to an extensive list
      of gene identifiers to review, which, in some cases, did not contain the relevant
      genes. The document retrieval suffered from the same shortfalls. The UAG favored
      achieving high performance (measured by precision and recall), but strongly
      recommended the addition of features that facilitate the identification of
      correct gene and its identifier, such as contextual information to assist in
      disambiguation. DISCUSSION: The IAT was an informative exercise that advanced the
      dialog between curators and developers and increased the appreciation of
      challenges faced by each group. A major conclusion was that the intended users
      should be actively involved in every phase of software development, and this will
      be strongly encouraged in future tasks. The IAT Task provides the first steps
      toward the definition of metrics and functional requirements that are necessary
      for designing a formal evaluation of interactive curation systems in the
      BioCreative IV challenge.

PMID- 22151969
TI  - Swedish emergency department triage and interventions for improved patient flows:
      a national update.
AB  - BACKGROUND: In Scandinavia, emergency department triage and patient flow
      processes, are under development. In Sweden, the triage development has resulted
      in two new triage scales, the Adaptive Process Triage and the Medical Emergency
      Triage and Treatment System. Both these scales have logistic components, aiming
      to improve patient flows. The aim of this study was to report the development and
      current status of emergency department triage and patient flow processes in
      Sweden. METHODS: In 2009 and 2010 the Swedish Council on Health Technology
      Assessment sent out a questionnaire to the ED managers in all (74) Swedish
      hospital emergency departments. The questionnaire comprised questions about
      triage and interventions to improve patient flows. RESULTS: Nearly all (97%) EDs
      in Sweden employed a triage scale in 2010, which was an increase from 2009 (73%).
      Further, the Medical Emergency Triage and Treatment System was the triage scale
      most commonly implemented across the country. The implementation of flow-related
      interventions was not as common, but more than half (59%) of the EDs have
      implemented or plan to implement nurse requested X-ray. CONCLUSIONS: There has
      been an increase in the use of triage scales in Swedish EDs during the last few
      years, with acceleration for the past two years. Most EDs have come to use the
      Medical Emergency Triage and Treatment System, which also indicates regional co
      operation. The implementation of different interventions for improved patient
      flows in EDs most likely is explained by the problem of crowding. Generally, more
      studies are needed to investigate the economical aspects of these interventions.

PMID- 22151970
TI  - Identification of conserved gene clusters in multiple genomes based on synteny
      and homology.
AB  - BACKGROUND: Uncovering the relationship between the conserved chromosomal
      segments and the functional relatedness of elements within these segments is an
      important question in computational genomics. We build upon the series of works
      on gene teams and homology teams. RESULTS: Our primary contribution is a local
      sliding-window SYNS (SYNtenic teamS) algorithm that refines an existing family
      structure into orthologous sub-families by analyzing the neighborhoods around the
      members of a given family with a locally sliding window. The neighborhood
      analysis is done by computing conserved gene clusters. We evaluate our algorithm
      on the existing homologous families from the Genolevures database over five
      genomes of the Hemyascomycete phylum. CONCLUSIONS: The result is an efficient
      algorithm that works on multiple genomes, considers paralogous copies of genes
      and is able to uncover orthologous clusters even in distant genomes. Resulting
      orthologous clusters are comparable to those obtained by manual curation.

PMID- 22151971
TI  - Heterologous overexpression of Glomerella cingulata FAD-dependent glucose
      dehydrogenase in Escherichia coli and Pichia pastoris.
AB  - BACKGROUND: FAD dependent glucose dehydrogenase (GDH) currently raises enormous
      interest in the field of glucose biosensors. Due to its superior properties such
      as high turnover rate, substrate specificity and oxygen independence, GDH makes
      its way into glucose biosensing. The recently discovered GDH from the ascomycete
      Glomerella cingulata is a novel candidate for such an electrochemical
      application, but also of interest to study the plant-pathogen interaction of a
      family of wide-spread, crop destroying fungi. Heterologous expression is a
      necessity to facilitate the production of GDH for biotechnological applications
      and to study its physiological role in the outbreak of anthracnose caused by
      Glomerella (anamorph Colletotrichum) spp. RESULTS: Heterologous expression of
      active G. cingulata GDH has been achieved in both Escherichia coli and Pichia
      pastoris, however, the expressed volumetric activity was about 4800-fold higher
      in P. pastoris. Expression in E. coli resulted mainly in the formation of
      inclusion bodies and only after co-expression with molecular chaperones enzymatic
      activity was detected. The fed-batch cultivation of a P. pastoris transformant
      resulted in an expression of 48,000 U L-1 of GDH activity (57 mg L-1).
      Recombinant GDH was purified by a two-step purification procedure with a yield of
      71%. Comparative characterization of molecular and catalytic properties shows
      identical features for the GDH expressed in P. pastoris and the wild-type enzyme
      from its natural fungal source. CONCLUSIONS: The heterologous expression of
      active GDH was greatly favoured in the eukaryotic host. The efficient expression
      in P. pastoris facilitates the production of genetically engineered GDH variants
      for electrochemical-, physiological- and structural studies.

PMID- 22151972
TI  - Early implementation of antifungal therapy in the management of febrile
      neutropenia is associated with favourable outcome during induction chemotherapy
      for acute leukaemias.
AB  - BACKGROUND: Mortality related to induction chemotherapy during the treatment of
      acute leukaemias (AL) has been estimated at 5-20%, and this increases with age.
      Fungal infection remains one of the major causes of morbidity and mortality and
      is considered an obstacle to the successful management of acute leukaemias.
      METHODS: We retrospectively analysed all patients treated for acute leukaemias at
      a single institution between July 2006 and January 2009, to assess the impact of
      early antifungal therapy on outcome during induction chemotherapy. There were 44
      episodes of induction chemotherapy, with a median age of patients of 61 years
      (range 18-81), including 29 patients with acute myeloid leukaemia, 9 with acute
      lymphoblastic leukaemia and 6 with relapsed AL. The median age was 61 years
      (range 18-81), and 20 patients were over the age of 60 years. RESULTS: All
      patients who developed febrile neutropenia received broad-spectrum antibiotics.
      Early empirical antifungal treatment was commenced with voriconazole (15
      patients) or caspofungin (12 patients) if the febrile neutropenia did not resolve
      after 72 h of antibiotic therapy, in conjunction with radiological changes
      consistent with possible fungal infection. None of the patients succumbed during
      induction chemotherapy. The 120-day mortality rate after the induction therapy
      was 2.2%, without any incidence of invasive fungal disease. CONCLUSION: Our
      analysis shows that early empirical treatment for fungal infection with
      voriconazole or caspofungin is associated with a favourable outcome of induction
      therapy for acute leukaemias. Further studies to confirm this finding are
      warranted.

PMID- 22151973
TI  - Zinc supplementation alters airway inflammation and airway hyperresponsiveness to
      a common allergen.
AB  - BACKGROUND: Zinc supplementation can modulate immunity through inhibition of NF
      kappaB, a transcription factor that controls many immune response genes. Thus, we
      sought to examine the mechanism by which zinc supplementation tempers the
      response to a common allergen and determine its effect on allergic airway
      inflammation. METHODS: Mice were injected with zinc gluconate prior to German
      cockroach (GC) feces (frass) exposure and airway inflammation was assessed.
      Primary bone marrow-derived neutrophils and DMSO-differentiated HL-60 cells were
      used to assess the role of zinc gluconate on tumor necrosis factor (TNF)alpha
      expression. NF-kappaB:DNA binding and IKK activity were assessed by EMSA and in
      vitro kinase assay. Protein levels of A20, RIP1 and TRAF6 were assessed by
      Western blot analysis. Establishment of allergic airway inflammation with GC
      frass was followed by administration of zinc gluconate. Airway
      hyperresponsiveness, serum IgE levels, eosinophilia and Th2 cytokine production
      were assessed. RESULTS: Administration of zinc gluconate prior to allergen
      exposure resulted in significantly decreased neutrophil infiltration and TNFalpha
      cytokine release into the airways. This correlated with decreased NF-kappaB
      activity in the whole lung. Treatment with zinc gluconate significantly decreased
      GC frass-mediated TNFalpha production from bone-marrow derived neutrophils and HL
      60 cells. We confirmed zinc-mediated decreases in NF-kappaB:DNA binding and IKK
      activity in HL-60 cells. A20, a natural inhibitor of NF-kappaB and a zinc
      fingered protein, is a potential target of zinc. Zinc treatment did not alter A20
      levels in the short term, but resulted in the degradation of RIP1, an important
      upstream activator of IKK. TRAF6 protein levels were unaffected. To determine the
      application for zinc as a therapeutic for asthma, we administered zinc following
      the establishment of allergic airway inflammation in a murine model. Zinc
      supplementation decreased airway hyperresponsiveness and serum IgE levels, but
      had no effect on Th2 cytokine expression. CONCLUSIONS: This report suggests that
      the mechanism by which zinc supplementation alters NF-kappaB activity is via the
      alteration of A20 activity. In addition, this study provides evidence that
      supplementation of zinc to asthmatics may alter airway reactivity and serum IgE
      levels, suggesting zinc supplementation as a potential treatment for asthmatics.

PMID- 22151974
TI  - Analysis of detergent-free lipid rafts isolated from CD4+ T cell line:
      interaction with antigen presenting cells promotes coalescing of lipid rafts.
AB  - BACKGROUND: Lipid rafts present on the plasma membrane play an important role in
      spatiotemporal regulation of cell signaling. Physical and chemical
      characterization of lipid raft size and assessment of their composition before,
      and after cell stimulation will aid in developing a clear understanding of their
      regulatory role in cell signaling. We have used visual and biochemical methods
      and approaches for examining individual and lipid raft sub-populations isolated
      from a mouse CD4+ T cell line in the absence of detergents. RESULTS: Detergent
      free rafts were analyzed before and after their interaction with antigen
      presenting cells. We provide evidence that the average diameter of lipid rafts
      isolated from un-stimulated T cells, in the absence of detergents, is less than
      100 nm. Lipid rafts on CD4+ T cell membranes coalesce to form larger structures,
      after interacting with antigen presenting cells even in the absence of a foreign
      antigen. CONCLUSIONS: Findings presented here indicate that lipid raft
      coalescence occurs during cellular interactions prior to sensing a foreign
      antigen.

PMID- 22151975
TI  - Prevention of falls and fractures in old people by administration of calcium and
      vitamin D, randomized clinical trial.
AB  - BACKGROUND: There are many studies that associate vitamin D serum levels in older
      persons with muscle strength, physical performance and risk of fractures and
      falls. However, current evidence is insufficient to make a general recommendation
      for administrating calcium and vitamin D to older persons. The objective of this
      study is to determine the effectiveness of calcium and vitamin D supplementation
      in improving musculoskeletal function and decreasing the number of falls in
      person aged over 65 years. METHODS/DESIGN: Phase III, randomized, double blind,
      placebo-controlled trial to evaluate the efficacy of already marketed drugs in a
      new indication. It will be performed at Primary Care doctor visits at several
      Healthcare Centers in different Spanish Health Areas. A total of 704 non
      institutionalized subjects aged 65 years or older will be studied (sample size
      calculated for a statistical power of 80%, alpha error 0.05, annual incidence of
      falls 30% and expected reduction of 30% to 20% and expected loss to follow up of
      20%). The test drug containing 800 IU of vitamin D and 1000 mg of calcium will be
      administered daily. The control group will receive a placebo. The subjects will
      be followed up over two years. The primary variable will be the incidence of
      spontaneous falls. The secondary variables will include: consequences of the
      falls (fractures, need for hospitalization), change in calcidiol plasma levels
      and other analytical determinations (transaminases, PTH, calcium/phosphorous,
      albumin, creatinine, etc.), change in bone mass by densitometry, change in muscle
      strength in the dominant hand and change in musculoskeletal strength, risk
      factors for falls, treatment compliance, adverse effects and socio-demographic
      data. DISCUSSION: The following principles have been considered in the
      development of this Project: the product data are sufficient to ensure that the
      risks assumed by the study participants are acceptable, the study objectives will
      probably provide further knowledge on the problem studied and the available
      information justifies the performance of the study and its possible risk for the
      participants.If calcium and vitamin D supplementation is effective in the
      prevention of falls and fractures in the elderly population, a recommendation may
      be issued with the aim of preventing some of the consequences of falls that
      affect quality of life and the ensuing personal, health and social costs. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01452243

PMID- 22151976
TI  - Cloning and characterization of a pectin lyase gene from Colletotrichum
      lindemuthianum and comparative phylogenetic/structural analyses with genes from
      phytopathogenic and saprophytic/opportunistic microorganisms.
AB  - BACKGROUND: Microorganisms produce cell-wall-degrading enzymes as part of their
      strategies for plant invasion/nutrition. Among these, pectin lyases (PNLs)
      catalyze the depolymerization of esterified pectin by a beta-elimination
      mechanism. PNLs are grouped together with pectate lyases (PL) in Family 1 of the
      polysaccharide lyases, as they share a conserved structure in a parallel beta
      helix. The best-characterized fungal pectin lyases are obtained from
      saprophytic/opportunistic fungi in the genera Aspergillus and Penicillium and
      from some pathogens such as Colletotrichum gloeosporioides.The organism used in
      the present study, Colletotrichum lindemuthianum, is a phytopathogenic fungus
      that can be subdivided into different physiological races with different
      capacities to infect its host, Phaseolus vulgaris. These include the non
      pathogenic and pathogenic strains known as races 0 and 1472, respectively.
      RESULTS: Here we report the isolation and sequence analysis of the Clpnl2 gene,
      which encodes the pectin lyase 2 of C. lindemuthianum, and its expression in
      pathogenic and non-pathogenic races of C. lindemuthianum grown on different
      carbon sources. In addition, we performed a phylogenetic analysis of the deduced
      amino acid sequence of Clpnl2 based on reported sequences of PNLs from other
      sources and compared the three-dimensional structure of Clpnl2, as predicted by
      homology modeling, with those of other organisms. Both analyses revealed an early
      separation of bacterial pectin lyases from those found in fungi and oomycetes.
      Furthermore, two groups could be distinguished among the enzymes from fungi and
      oomycetes: one comprising enzymes from mostly saprophytic/opportunistic fungi and
      the other formed mainly by enzymes from pathogenic fungi and oomycetes. Clpnl2
      was found in the latter group and was grouped together with the pectin lyase from
      C. gloeosporioides. CONCLUSIONS: The Clpnl2 gene of C. lindemuthianum shares the
      characteristic elements of genes coding for pectin lyases. A time-course analysis
      revealed significant differences between the two fungal races in terms of the
      expression of Clpnl2 encoding for pectin lyase 2. According to the results,
      pectin lyases from bacteria and fungi separated early during evolution. Likewise,
      the enzymes from fungi and oomycetes diverged in accordance with their differing
      lifestyles. It is possible that the diversity and nature of the assimilatory
      carbon substrates processed by these organisms played a determinant role in this
      phenomenon.

PMID- 22151978
TI  - International Conference on Prevention & Infection Control (ICPIC 2011) Geneva,
      Switzerland.  29 June - 2 July 2011. Abstracts.

PMID- 22151977
TI  - Choroidal metastases in testicular choriocarcinoma, successful treatment with
      chemo- and radiotherapy: a case report.
AB  - BACKGROUND: Choriocarcinoma is a very rare cause of ocular metastasis. Only 18
      male patients have been reported on, 4 of whom survived, but with significant
      loss of vision. CASE PRESENTATION: A 26-year-old Caucasian man, suffering from
      testicular choriocarcinoma with pulmonary, cerebral, renal, hepatic and osseous
      metastases, underwent left radical orchiectomy. While being treated with
      chemotherapy, he presented with loss of vision in the left eye. Ophthalmoscopy
      revealed bilateral non-pigmented, hemorrhagic choroidal tumours, compatible with
      secondary lesions. Continued chemotherapy and stereotactic radiotherapy of the
      skull and spine lead to full remission with excellent vision, after more than 4
      years of follow up. CONCLUSION: Testicular choriocarcinoma is an exceptional
      cause of choroidal metastasis, potentially asymptomatic and with specific
      clinical features. Radiotherapy can complement radical orchiectomy and
      chemotherapy, to achieve full remission and maintain good vision.

PMID- 22151979
TI  - Gastroenteritis outbreak associated with faecal shedding of canine norovirus in a
      Portuguese kennel following introduction of imported dogs from Russia.
AB  - We describe an outbreak of acute gastroenteritis (AGE) in dogs in March 2011 in a
      Portuguese kennel after the introduction of imported Russian dogs. Canine
      norovirus was detected in faecal samples of all dogs with AGE symptoms. Partial
      sequence analysis of the RT-PCR products confirmed that all canine norovirus
      strains were identical. The canine norovirus infection disseminated rapidly in 2
      days to all dogs in the kennel demonstrating the highly contagious nature of this
      virus. The incubation period was <48 h, the diarrhoeal disease was self-limiting
      and the viral shedding lasted <7 days. Overall, the epidemiological features of
      this outbreak resembled those of human norovirus infections.

PMID- 22151980
TI  - Cancer in Australia: a model for other Asia-Pacific countries.

PMID- 22151981
TI  - Cancer in Australia: actual incidence and mortality data from 1982 to 2007 and
      projections to 2010.
AB  - BACKGROUND: The Australian Institute of Health and Welfare and the Australasian
      Association of Cancer Registries collaborate every year to provide updated
      information on cancer occurrences and trends in Australia. METHOD: Actual number
      of cases and deaths is presented together with age-standardised rates for all
      cancers combined and selected cancer sites from 1982 to 2007, with projections to
      2010. Differences in incidence and mortality rates according to age, Indigenous
      status and remoteness areas are also provided. In addition, change over time in 5
      year relative survival estimates for those diagnosed with cancer is presented, as
      is information on the participation in Australia's national screening programs
      for breast, cervical and bowel cancer. The term 'cancer' is used to refer to
      primary tumours which are invasive. RESULTS: In 2007, a total of 108,368 new
      cases of cancer (excluding basal and squamous cell carcinoma of the skin) and
      39,884 deaths from cancer occurred in Australia. Prostate cancer was the most
      commonly diagnosed cancer in males, while breast cancer was the most commonly
      diagnosed cancer in females. Lung cancer was by far the most common cause of
      cancer death in both males and females. In the last decade, cancer incidence
      rates increased in males and stabilised in females, while mortality rates
      decreased steadily. The overall incidence rate of cancer for Indigenous
      Australians was lower than that for non-indigenous Australians, while the overall
      mortality rate from cancer was higher. Furthermore, the 5-year relative survival
      for many cancers improved markedly from 1982-1986 to 1998-2004.

PMID- 22151982
TI  - Expression of telomere binding proteins in gastric cancer and correlation with
      clinicopathological parameters.
AB  - AIM: The aim of this study was to investigate the expression of telomere repeat
      binding factor 1 (TRF1), TRF2 and protection of telomeres 1 (POT1) in gastric
      cancer and their relationships with clinicopathological features and telomerase
      activity. METHODS: In total 36 gastric cancer tissue and paired adjacent normal
      tissue were analyzed. The mRNA expression of telomere binding proteins TRF1, TRF2
      and POT1 were measured using quantitative reverse transcription polymerase chain
      reaction, and telomerase activity was assessed by the telomeric repeat
      amplification protocol/enzyme linked immunosorbent assay method. RESULTS: The
      expression of POT1 was significantly higher in tumor tissue than in adjacent
      normal tissue (P < 0.001). Levels of TRF2 mRNA were significantly higher in
      bigger tumors (diameter >= 5 cm) than in small tumors (diameter < 5 cm) (P =
      0.043). POT1 mRNA transcription levels were higher in tumors with lymph nodes
      metastases than in those without lymph nodes metastases (P = 0.048). POT1
      expression was significantly correlated with tumor stage (P = 0.008). A higher
      level of expression of POT1 was observed in late-stage tumors (III, IV) than in
      early stage tumors (I, II). Telomerase activity was significantly higher in
      gastric cancers than in corresponding normal tissue (P < 0.001). Moreover, POT1
      expression was significantly positive correlated with telomerase activity (r =
      0.572, P < 0.01). CONCLUSION: POT1 was overexpressed in gastric cancer and may be
      associated with stomach carcinogenesis and gastric cancer progression.

PMID- 22151983
TI  - Cytogenetic analysis of de novo CD5-positive diffuse large B-cell lymphoma.
AB  - AIMS: De novo CD5-positive diffuse large B cell lymphoma (CD5+DLBL) is a subtype
      of DLBL with poor clinical outcome. To investigate the cytogenetic pathogenesis
      of CD5+DLBL, we analyzed the chromosomal findings of 18 patients with CD5+DLBL.
      METHODS: Tumor cells were cultured and metaphase was captured by colchicine
      exposure. Using trypsin-Giemsa banding, the chromosomes were analyzed according
      to the International System for Human Cytogenetic Nomenclature. RESULTS:
      Metaphase was acquired from 12 patients. Normal karyotypes were seen in two
      patients and abnormal karyotypes in the remaining 10. The numbers of chromosomes
      ranged from 45 to 90. Gain, loss and rearrangements of various chromosomes were
      seen. Frequent breakpoints were located at chromosome 1 band p13, 3q27, 6q13,
      7q32, 14q32, 18q21 and 19q13. There was no diagnosis-specific abnormality. A
      relationship between chromosomal findings and clinical outcomes such as involved
      site, relapse or survival, was not observed. CONCLUSION: Since previous and the
      present studies on the chromosomal analysis of CD5+DLBL are also contradictory,
      more detailed comprehensive genetic analysis appears to be needed to elucidate
      the biological mechanisms of CD5+DLBL.

PMID- 22151984
TI  - Management of tumor lysis syndrome with a single fixed dose of rasburicase in
      Asian lymphoma patients: a case series and literature review.
AB  - AIM: Recently, a number of studies have demonstrated the effectiveness of a
      single reduced dose of rasburicase for the management of tumor lysis syndrome
      (TLS) in adults. Whether Asian lymphoma patients similarly respond to a single
      dose of rasburicase is currently unknown. We aim to assess the efficacy of a
      single dose rasburicase in preventing TLS in Asian lymphoma patients. METHODS:
      This was a single-center case series of adult lymphoma patients at high risk of
      TLS who received a single fixed dose of rasburicase. Patients had to have their
      uric acid, serum creatinine, lactate dehydrogenase and electrolytes monitored for
      at least 24-48 h post-administration. RESULTS: Eleven patients were identified.
      Majority were Chinese (91%), male (64%) and with a median age of 61 years (range
      41-84). All had at least two risk factors for developing TLS. Ten patients
      received a 6-mg dose and one received 4.5 mg. Prior to rasburicase
      administration, the mean uric acid level was 835 umol/L (range 318-1237 umol/L)
      and the level 24-h post-administration was 186 umol/L (range 30-653 umol/L) (P <
      0.001). Eight patients (73%) experienced an improvement of renal function 72-h
      post-rasburicase. Normalization of serum electrolytes was achieved within 96 h.
      CONCLUSION: Among Asian lymphoma patients who manifested at least two risk
      factors for developing TLS, a single fixed dose of rasburicase at 6 mg is deemed
      to be effective for rapidly lowering uric acid levels as well as sustaining
      reduced levels for up to 72 h.

PMID- 22151985
TI  - eviQ cancer treatments online: how does the web-based protocol system fare in a
      comprehensive quality assessment?
AB  - AIMS: There have been few evaluations of the quality of computerized decision
      support tools in medical oncology despite their widespread use in clinical
      practice. In this article, we provide an in-depth quality assessment of eviQ, an
      Australian web-based protocol system. METHODS: We used the Appraisal of
      Guidelines for Research and Evaluation (AGREE-II) instrument to examine the
      quality of eviQ chemotherapy protocols across six domains: scope and purpose,
      stakeholder involvement, rigor of development, clarity of presentation,
      applicability, editorial independence and overall quality rating. Domain scores
      were categorized as high quality (scores of >70%), moderate quality (30-70%), and
      low quality (<30%). RESULTS: eviQ was rated highly with respect to articulating
      its scope and purpose, clarity of presentation, applicability and on the overall
      rating item (scores of 72-80%). Domains addressing the involvement of
      stakeholders in the development process and the rigor with which protocols were
      developed were of moderate quality (scores of 34-37%) and the management of
      editorial independence and conflict of interest issues were rated in the low
      quality range (22%). CONCLUSION: Our evaluation demonstrated the eviQ protocol
      system is generally of high quality. However, we identified a number of areas in
      which eviQ could improve either its development processes or the means by which
      these processes are communicated to end-users. This research represents the first
      comprehensive evaluation of oncology protocols and paves the way for continued
      quality assurance research to ensure that these tools meet their objective of
      facilitating evidence-based medicine, standardizing treatment and, ultimately,
      improving patient outcomes.

PMID- 22151986
TI  - The adverse implications of the transition from film to digital mammography for
      performing surveillance in patients with a history of breast cancer or
      significant risk factors for the disease.
AB  - AIM: The transition from screen-film to digital mammography at Peter MacCallum
      Cancer Centre was investigated, considering the impact on patient management and
      resource utilization. METHODS: A retrospective comparison of the imaging outcomes
      of the last year of screen-film and the first year of digital mammography was
      performed. The study group of 692 patients, all with a history or a significant
      risk factor of breast cancer, underwent a surveillance mammogram in both periods,
      enabling serial comparison of imaging outcomes on the same patient. RESULTS:
      Overall 92 patients required a total of 125 further investigations after their
      film mammogram due to a mammographic abnormality while 130 underwent a total of
      202 additional investigations after their digital mammogram. This is a
      significant increase in the number of patients further investigated (Fisher's
      exact test P = 0.005). However, the positive predictive value of further
      investigation finding a tumor after digital mammography was not significantly
      higher than that of film mammography (7.4 vs 6.5%, Fisher's exact test P = 0.57).
      There was a 44% increase in the cost of additional investigations during the
      first year of digital mammography compared to the previous year and an associated
      increase in hospital visits for patients. CONCLUSION: For patients undergoing
      annual surveillance mammography at Peter MacCallum Cancer Centre, the transition
      from film to digital mammography was found to be associated with an increase in
      both the number of additional investigations performed and in the number of
      hospital visits. The findings of this study should be considered when conversions
      from film to digital mammography are planned, specifically in terms of cost
      allocations and the burden on patient services in radiology and outpatient
      departments.

PMID- 22151987
TI  - Cost-effectiveness analysis of cisplatin plus etoposide and carboplatin plus
      paclitaxel in a phase III randomized trial for non-small cell lung cancer.
AB  - AIM: Carboplatin plus paclitaxel is a more costly chemotherapy regimen than
      cisplatin plus etoposide; however there have been reports of higher efficacy and
      less toxicity of this regimen. Thus, this study aimed to assess the cost
      effectiveness of these two chemotherapy regimens in advanced non-small cell lung
      cancer (NSCLC). METHODS: Using the perspective of Maharaj Nakorn Chiang Mai
      Hospital, Thailand, direct medical costs, including chemotherapy, drugs, medical
      service charges, costs of adverse events, concomitant medication and survival
      time were directly gathered from 65 patients enrolled from August 2005 to
      November 2008. A one-way sensitivity analysis was performed. An incremental cost
      effectiveness ratio (ICER) was also calculated. RESULTS: Of these 65 patients, 30
      received cisplatin plus etoposide (Arm I) and 35 received carboplatin plus
      paclitaxel (Arm II). The median survival time was not statistically significant
      (8.23 months vs 8.80 months in Arm I and II, respectively; P = 0.99). The total
      cost per patient in Arm II was about three times that in Arm I (95,548 Baht vs
      29,692 Baht) while quality-adjusted life-years (QALY) in Arm II were slightly
      above those in Arm I (0.587 vs 0.412). The ICER was equal to 375,958 Baht per
      QALY. CONCLUSION: With a cost-effectiveness threshold of 100,000 Baht in
      Thailand, carboplatin plus paclitaxel was still not cost-effective. While the
      selection of a suitable regimen for individual patients should not rely on drug
      and hospital costs alone, the overall cost, including the burden on patients,
      should be taken into consideration.

PMID- 22151988
TI  - Randomized phase 2 sequencing and pharmacokinetic study of gemcitabine and
      oxaliplatin in advanced non-small cell lung cancer.
AB  - AIM: This multicentre phase II trial examined the combination of gemcitabine and
      oxaliplatin in patients with advanced non-small cell lung cancer (NSCLC). The
      effect of sequence administration was randomized and pharmacokinetics (PK)
      assessed. METHODS: Eligible patients had stage IIIB or IV or recurrent NSCLC, no
      prior chemotherapy, World Health Organization performance status <=2 and
      measurable disease. Treatment comprised: gemcitabine (1250 mg/m(2)) and
      oxaliplatin (70 mg/m(2)), each given on days 1 and 8 of a 21-day cycle. Patients
      were randomized 1:1 to the sequencing of the two drugs for the duration of their
      treatment. The primary end-point was response rate (RR). Secondary end-points
      included progression-free survival (PFS), overall survival (OS), toxicity, PK and
      the effect of drug sequencing. RESULTS: A total of 46 patients were enrolled of
      whom 43 were evaluable for response. Overall 13 patients (30%) achieved a partial
      response, PFS was 4.2 months (95% CI 2.8-5.8 months), and OS was 6.8 months (95%
      CI 4.4-10.1 months). There was only one case of grade 3 neurosensory toxicity
      despite a median cumulative oxaliplatin dose in excess of 500 mg/m(2) . No
      differences in clinical or PK end-points were observed between the two different
      sequencing arms. CONCLUSION: This oxaliplatin and gemcitabine schedule has shown
      activity in advanced NSCLC with modest toxicity. Neither clinical nor PK outcomes
      were influenced by the sequencing of these agents, although definite conclusions
      are limited by small patient numbers. The favorable toxicity profile of this
      doublet, in light of an encouraging RR, warrants its further investigation in
      NSCLC.

PMID- 22151989
TI  - Aberrant expression and clinical correlation of Notch signaling molecules in
      breast cancer of Chinese population.
AB  - AIMS: Notch signaling molecules play crucial roles in cell proliferation and
      apoptosis, yet their function in breast cancer remains unclear. METHODS: Samples
      and clinical data from 62 breast cancer patients were collected. After total RNA
      isolation, reverse transcription polymerase chain reaction was applied to analyze
      the expression of Notch receptors (Notch1, Notch3 and Notch4) and ligands (DLL4
      and JAG1), and their clinical association. Immunohistochemical analysis was used
      to detect the intracellular domain of Notch1 (Notch1-IC) expression. RESULTS:
      Notch1 was the dominant receptor while DLL4 was the dominant ligand. The Notch
      molecules expression pattern for infiltrating ductal carcinoma (IDC) was similar
      to that for infiltrating lobular carcinoma (ILC) except for JAG1, while Notch1
      standard coefficients in ILC were statistically higher than that in IDC.
      Immunohistochemical results showed that Notch1-IC protein expression paralleled
      the mRNA level. Breast cancer patients' clinical parameters suggested that Notch1
      expression was higher in stage II disease and lower in more advanced stages. The
      Notch3 positive rate was higher in patients with lower levels of Notch1, and the
      Notch3 positive rate was lower in patients with higher levels of Notch1. No
      apparent correlation of Notch molecules with estrogen receptor (ER), progesterone
      receptor (PR) was found. Though high Notch1 and Notch3 RNA levels tended to
      correlate with c-erbB2 expression, no statistical significance was found.
      CONCLUSION: Notch molecules are useful biomarkers in breast cancer especially for
      Notch1 and DLL4, and Notch1 is expressed differently in different stages of human
      breast cancer.

PMID- 22151990
TI  - Endothelial cell damage induces a blood-alveolus barrier breakdown in the
      development of radiation-induced lung injury.
AB  - AIM: To investigate the role of endothelial cell damage in radiation-induced lung
      injury. METHODS: A total of 60 male Sprague-Dawley rats were irradiated to the
      right hemithorax with a single dose of 0, 7.0 or 14.4 Gy. Serial studies were
      performed before and at 1, 7, 30 and 90 days after radiation, respectively.
      Pathological studies were carried out to detect changes in the lung after
      irradiation. Western blot studies were conducted to detect the expression of CD34
      and of CD105 and vascular endothelial growth factor (VEGF). RESULTS: Compared to
      controls, the irradiated rat lung showed a dose-dependent and time-dependent
      decrease in the expression of CD34. The level of CD105 was significantly reduced
      by irradiation except at 90 days after radiation. The expression of VEGF
      increased 1 day after radiation, and then decreased from day 30 onwards, to be
      lower than the control group at 90 days. Pulmonary fibrosis was observed at 90
      days after 14.4 Gy exposure; however, most of these phenomena were not observed
      in the 7.0 Gy group. CONCLUSION: These results support the notion that
      endothelial cells play an important role in radiation-induced lung injury, and
      may be critical to breakdown of the blood-alveolus barrier and microcirculation
      dysfunction related to radiation-induced inflammation and fibrosis.

PMID- 22151991
TI  - Neoplastic infiltration of the sphenoid wing: a rare manifestation of metastatic
      colorectal cancer.
AB  - Atypical patterns of metastatic spread from colorectal primary tumors are often
      misdiagnosed, with potential implications for the clinical outcome. Metastatic
      diffusion to the splanchnocranium is extremely rare in colorectal cancer. A
      histological proof of diagnosis is rarely obtained and therapeutic management is
      a challenge. We describe the case of a 46-year-old patient who presented with a
      radiologically proven sphenoid wing metastasis. The patient presented with left
      sided exophthalmos while receiving systemic chemotherapy for relapsed high-risk
      colorectal cancer. A left sphenoid wing metastasis was proven by a head computed
      tomography scan. A metastatic spread to the sino-nasal tract is regarded as a
      poor prognosis determinant in colorectal cancer and presents a unique set of
      diagnostic and therapeutic challenges. The compression of noble structures such
      as the optic nerve holds serious implications in terms of quality of life but
      there is insufficient evidence clarifying whether radiotherapy or surgery
      represent the best option for these patients, leaving the therapeutic plan to be
      decided case by case.

PMID- 22151992
TI  - Training opportunities in geriatric oncology.

PMID- 22151995
TI  - Structural evolution of GeMn/Ge superlattices grown by molecular beam epitaxy
      under different growth conditions.
AB  - GeMn/Ge epitaxial 'superlattices' grown by molecular beam epitaxy with different
      growth conditions have been systematically investigated by transmission electron
      microscopy. It is revealed that periodic arrays of GeMn nanodots can be formed on
      Ge and GaAs substrates at low temperature (approximately 70 degrees C) due to the
      matched lattice constants of Ge (5.656 A) and GaAs (5.653 A), while a periodic
      Ge/GeMn superlattice grown on Si showed disordered GeMn nanodots with a large
      amount of stacking faults, which can be explained by the fact that Ge and Si have
      a large lattice mismatch. Moreover, by varying growth conditions, the GeMn/Ge
      superlattices can be manipulated from having disordered GeMn nanodots to ordered
      coherent nanodots and then to ordered nanocolumns.PACS: 75.50.Pp; 61.72.-y;
      66.30.Pa; 68.37.L.

PMID- 22151996
TI  - A case-cohort study of human herpesvirus 8 seropositivity and incident prostate
      cancer in Tobago.
AB  - BACKGROUND: We previously reported a cross-sectional association between the
      presence of human herpesvirus 8 (HHV-8) serum antibodies and screen-detected
      prostate cancer in men living in Tobago. In the same study population, we
      examined the association between HHV-8 seropositivity and incident prostate
      cancer discovered at later screenings. METHODS: In 40-81 year-old men without
      prostate cancer discovered at initial digital rectal examination (DRE) and
      prostate-specific antigen (PSA) screening, a case-cohort design measured the
      association between baseline HHV-8 seropositivity (modified immunofluorescence
      assay for antibodies against HHV-8 lytic antigens) and incident prostate cancer
      detected at DRE and PSA screenings three or five years later. RESULTS: Analyses
      included 486 unique individuals, 96 incident prostate cancer cases, and 415
      randomly selected subjects representing an at-risk cohort. By design, the random
      sub-cohort contained 25 incident prostate cancer cases. In the sub-cohort, the
      frequency of HHV-8 seropositivity increased across age groupings (40-49 years:
      3.5%, 50-59 years: 13.6%, and >= 60 years: 22.9%). HHV-8 seropositivity was
      higher in men with elevated (>= 4.0 ng/mL) than men with non-elevated PSA at
      initial screening (30.4% vs. 9.9% seropositive; crude odds ratio (OR) 3.96, 95%
      confidence interval (CI) 1.53-10.2; age-adjusted OR 2.42, 95% CI 0.91-6.47). HHV
      8 seropositivity did not increase incident prostate cancer risk (age-adjusted
      hazard ratio (HR) 0.88, 95% CI 0.46-1.69). CONCLUSIONS: Case-cohort analysis did
      not identify association between HHV-8 seropositivity and incident prostate
      cancer. However, analyses uncovered possible association between HHV-8 and PSA (a
      marker of prostate inflammation). Co-occurrence of HHV-8 seropositivity and PSA
      elevation may explain cross-sectional association between HHV-8 and PSA screen
      detected prostate cancer.

PMID- 22151997
TI  - Regulation of breast cancer metastasis by Runx2 and estrogen signaling: the role
      of SNAI2.
AB  - INTRODUCTION: In contrast to its role in breast cancer (BCa) initiation, estrogen
      signaling has a protective effect in later stages, where estrogen receptor
      (ER)alpha loss associates with aggressive metastatic disease. We asked whether
      the beneficial effect of estrogen signaling in late-stage BCa is attributable to
      the recently reported estrogen-mediated antagonism of the pro-metastatic
      transcription factor Runx2. METHODS: MCF7/Rx2dox breast cancer cells were
      engineered with a lentivirus expressing Runx2 in response to doxycycline (dox).
      Cells treated with dox and/or estradiol (E2) were subjected to genome-wide
      expression profiling, RT-qPCR analysis of specific genes, and MatrigelTM invasion
      assays. Knockdown of genes of interest was performed using lentiviruses
      expressing appropriate shRNAs, either constitutively or in response to dox. Gene
      expression in BCa tumors was investigated using a cohort of 557 patients compiled
      from publicly available datasets. Association of gene expression with clinical
      metastasis was assessed by dichotomizing patients into those expressing genes of
      interest at either high or low levels, and comparing the respective Kaplan-Meier
      curves of metastasis-free survival. RESULTS: Runx2 induced epithelial-mesenchymal
      transition (EMT) evidenced by acquisition of a fibroblastic morphology, decreased
      expression of E-cadherin, increased expression of vimentin and invasiveness.
      Runx2 stimulated SNAI2 expression in a WNT- and transforming growth factor
      (TGF)beta-dependent manner, and knockdown of SNAI2 abrogated the pro-metastatic
      activities of Runx2. E2 antagonized the pro-metastatic activities of Runx2,
      including SNAI2 upregulation. In primary BCa tumors, Runx2 activity, SNAI2
      expression, and metastasis were positively correlated, and SNAI2 expression was
      negatively correlated with ERalpha. However, the negative correlation between
      SNAI2 and ERalpha in bone-seeking BCa cells was weaker than the respective
      negative correlation in tumors seeking lung. Furthermore, the absence of ERalpha
      in primary tumors was associated with lung- and brain- but not with bone
      metastasis, and tumor biopsies from bone metastatic sites displayed the unusual
      combination of high Runx2/SNAI2 and high ERalpha expression. CONCLUSIONS: E2
      antagonizes Runx2-induced EMT and invasiveness of BCa cells, partly through
      attenuating expression of SNAI2, a Runx2 target required for mediating its pro
      metastatic property. That ERalpha loss promotes non-osseous metastasis by
      unleashing Runx2/SNAI2 is supported by the negative correlation observed in
      corresponding tumors. Unknown mechanisms in bone-seeking BCa allow high
      Runx2/SNAI2 expression despite high ERalpha level.

PMID- 22151998
TI  - Antagonistic pleiotropy as a widespread mechanism for the maintenance of
      polymorphic disease alleles.
AB  - BACKGROUND: Many serious diseases have a genetic basis which, from an
      evolutionary point of view, should have been selected against, resulting in very
      low frequencies. The remarkable sustained prevalence of a number of disease
      associated alleles is therefore surprising. We believe that antagonistic
      pleiotropy, when multiple effects of a gene have opposing effects on fitness
      (e.g., sickle cell disease), may be more widespread than typically considered. We
      hypothesize that, rather than being an exception to the rule of genetic
      disorders, antagonistic pleiotropy may be common. METHODS: We surveyed the
      medical literature in order to determine whether sufficient evidence exists to
      reassess the nature of antagonistic pleiotropy; from being considered an unusual
      scenario to one that is anticipated. We also used a simple population genetic
      model to examine the feasibility of antagonistic pleiotropy to act as a mechanism
      to maintain polymorphism for serious genetic disorders even if the benefits are
      subtle. RESULTS: We identified a number of examples of antagonistic pleiotropy
      where the deleterious effect, the beneficial effect, and the exact molecular
      cause have been demonstrated. We also identified putative cases in which there is
      circumstantial evidence or a strong reason to expect antagonistic pleiotropy in a
      genetic disorder. The population genetic model demonstrates that alleles with
      severe deleterious health effects can be maintained at medically relevant
      frequencies with only minor beneficial pleiotropic effects. CONCLUSION: We
      believe that our identification of several cases of antagonistic pleiotropy,
      despite the lack of research on this question and the varied natures of the types
      of these disorders, speaks to both the underappreciated nature of this phenomenon
      and its potentially fundamental importance. If antagonistic pleiotropy is as
      common as our research suggests, this may explain why so many serious diseases,
      even apparently environmentally caused ones, have a genetic component.
      Furthermore, acceptance of a genome full of antagonistically pleiotropic genetic
      interactions poses important implications for clinical treatment and disease
      prevention research, especially genetically based therapies.

PMID- 22151999
TI  - Cross-species gene normalization by species inference.
AB  - BACKGROUND: To access and utilize the rich information contained in the
      biomedical literature, the ability to recognize and normalize gene mentions
      referenced in the literature is crucial. In this paper, we focus on improvements
      to the accuracy of gene normalization in cases where species information is not
      provided. Gene names are often ambiguous, in that they can refer to the genes of
      many species. Therefore, gene normalization is a difficult challenge. METHODS: We
      define "gene normalization" as a series of tasks involving several issues,
      including gene name recognition, species assignation and species-specific gene
      normalization. We propose an integrated method, GenNorm, consisting of three
      modules to handle the issues of this task. Every issue can affect overall
      performance, though the most important is species assignation. Clearly, correct
      identification of the species can decrease the ambiguity of orthologous genes.
      RESULTS: In experiments, the proposed model attained the top-1 threshold average
      precision (TAP-k) scores of 0.3297 (k=5), 0.3538 (k=10), and 0.3535 (k=20) when
      tested against 50 articles that had been selected for their difficulty and the
      most divergent results from pooled team submissions. In the silver-standard-507
      evaluation, our TAP-k scores are 0.4591 for k=5, 10, and 20 and were ranked 2nd,
      2nd, and 3rd respectively. AVAILABILITY: A web service and input, output formats
      of GenNorm are available at http://ikmbio.csie.ncku.edu.tw/GN/.

PMID- 22152000
TI  - CXCR3 chemokine ligands during respiratory viral infections predict lung
      allograft dysfunction.
AB  - Community-acquired respiratory viruses (CARV) can accelerate the development of
      lung allograft dysfunction, but the immunologic mechanisms are poorly understood.
      The chemokine receptor CXCR3 and its chemokine ligands, CXCL9, CXCL10 and CXCL11
      have roles in the immune response to viruses and in the pathogenesis of
      bronchiolitis obliterans syndrome, the predominant manifestation of chronic lung
      allograft rejection. We explored the impact of CARV infection on CXCR3/ligand
      biology and explored the use of CXCR3 chemokines as biomarkers for subsequent
      lung allograft dysfunction. Seventeen lung transplant recipients with CARV
      infection had bronchoalveolar lavage fluid (BALF) available for analysis. For
      comparison, we included 34 BALF specimens (2 for each CARV case) that were
      negative for infection and collected at a duration posttransplant similar to a
      CARV case. The concentration of each CXCR3 chemokine was increased during CARV
      infection. Among CARV infected patients, a high BALF concentration of either
      CXCL10 or CXCL11 was predictive of a greater decline in forced expiratory volume
      in 1 s, 6 months later. CXCR3 chemokine concentrations provide prognostic
      information and this may have important implications for the development of novel
      treatment strategies to modify outcomes after CARV infection.

PMID- 22152001
TI  - Association between a single-pass whole-body computed tomography policy and
      survival after blunt major trauma: a retrospective cohort study.
AB  - INTRODUCTION: Single-pass, whole-body computed tomography (pan-scan) remains a
      controversial intervention in the early assessment of patients with major trauma.
      We hypothesized that a liberal pan-scan policy is mainly an indicator of enhanced
      process quality of emergency care that may lead to improved survival regardless
      of the actual use of the method. METHODS: This retrospective cohort study
      included consecutive patients with blunt trauma referred to a trauma center prior
      to (2000 to 2002) and after (2002 to 2007) the introduction of a liberal single
      pass pan-scan policy. The overall mortality between the two periods was compared
      and stratified according to the availability and actual use of the pan-scan.
      Logistic regression analysis was employed to adjust mortality estimates for
      demographic and injury-related independent variables. RESULTS: The study
      comprised 313 patients during the pre-pan-scan period, 223 patients after the
      introduction of the pan-scan policy but not undergoing a pan-scan and 608
      patients undergoing a pan-scan. The overall mortality was 23.3, 14.8 and 7.9% (P
      < 0.001), respectively. By univariable logistic regression analysis, both the
      availability (odds ratio (OR) 0.57, 95% confidence interval (CI): 0.36 to 0.90)
      and the actual use of the pan-scan (OR 0.28, 95% CI: 0.19 to 0.42) were
      associated with a lower mortality. The final model contained the Injury Severity
      Score, the Glasgow Coma Scale, age, emergency department time and the use of the
      pan-scan. 2.7% of the explained variance in mortality was attributable to the use
      of the pan-scan. This contribution increased to 7.1% in the highest injury
      severity quartile. CONCLUSIONS: In this study, a liberal pan-scan policy was
      associated with lower trauma mortality. The causal role of the pan-scan itself
      must be interpreted in the context of improved structural and process quality, is
      apparently moderate and needs further investigation with regard to the diagnostic
      yield and changes in management decisions. (The Pan-Scan for Trauma Resuscitation
      [PATRES] Study Group, ISRCTN35424832 and ISRCTN41462125).

PMID- 22152002
TI  - Rotavirus nonstructural protein 1 antagonizes innate immune response by
      interacting with retinoic acid inducible gene I.
AB  - BACKGROUND: The nonstructural protein 1 (NSP1) of rotavirus has been reported to
      block interferon (IFN) signaling by mediating proteasome-dependent degradation of
      IFN-regulatory factors (IRFs) and (or) the beta-transducin repeat containing
      protein (beta-TrCP). However, in addition to these targets, NSP1 may subvert
      innate immune responses via other mechanisms. RESULTS: The NSP1 of rotavirus OSU
      strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain
      are unable to degrade IRFs, but can still inhibit host IFN response, indicating
      that NSP1 may target alternative host factor(s) other than IRFs. Overexpression
      of NSP1 can block IFN-beta promoter activation induced by the retinoic acid
      inducible gene I (RIG-I), but does not inhibit IFN-beta activation induced by the
      mitochondrial antiviral-signaling protein (MAVS), indicating that NSP1 may target
      RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I
      independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of
      RIG-I in a proteasome-independent way. CONCLUSIONS: Our findings demonstrate that
      inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the
      immune evasion of rotavirus.

PMID- 22152004
TI  - Changes in transcriptional orientation are associated with increases in
      evolutionary rates of enterobacterial genes.
AB  - BACKGROUND: Changes in transcriptional orientation ("CTOs") occur frequently in
      prokaryotic genomes. Such changes usually result from genomic inversions, which
      may cause a conflict between the directions of replication and transcription and
      an increase in mutation rate. However, CTOs do not always lead to the replication
      transcription confrontation. Furthermore, CTOs may cause deleterious disruptions
      of operon structure and/or gene regulations. The currently existing CTOs may
      indicate relaxation of selection pressure. Therefore, it is of interest to
      investigate whether CTOs have an independent effect on the evolutionary rates of
      the affected genes, and whether these genes are subject to any type of selection
      pressure in prokaryotes. METHODS: Three closely related enterbacteria,
      Escherichia coli, Klebsiella pneumoniae and Salmonella enterica serovar
      Typhimurium, were selected for comparisons of synonymous (dS) and nonsynonymous
      (dN) substitution rate between the genes that have experienced changes in
      transcriptional orientation (changed-orientation genes, "COGs") and those that do
      not (same-orientation genes, "SOGs"). The dN/dS ratio was also derived to
      evaluate the selection pressure on the analyzed genes. Confounding factors in the
      estimation of evolutionary rates, such as gene essentiality, gene expression
      level, replication-transcription confrontation, and decreased dS at gene
      terminals were controlled in the COG-SOG comparisons. RESULTS: We demonstrate
      that COGs have significantly higher dN and dS than SOGs when a series of
      confounding factors are controlled. However, the dN/dS ratios are similar between
      the two gene groups, suggesting that the increase in dS can sufficiently explain
      the increase in dN in COGs. Therefore, the increases in evolutionary rates in
      COGs may be mainly mutation-driven. CONCLUSIONS: Here we show that CTOs can
      increase the evolutionary rates of the affected genes. This effect is independent
      of the replication-transcription confrontation, which is suggested to be the
      major cause of inversion-associated evolutionary rate increases. The real cause
      of such evolutionary rate increases remains unclear but is worth further
      explorations.

PMID- 22152005
TI  - High-yield production of biologically active recombinant protein in shake flask
      culture by combination of enzyme-based glucose delivery and increased oxygen
      transfer.
AB  - This report describes the combined use of an enzyme-based glucose release system
      (EnBase(r)) and high-aeration shake flask (Ultra Yield FlaskTM). The benefit of
      this combination is demonstrated by over 100-fold improvement in the active yield
      of recombinant alcohol dehydrogenase expressed in E. coli. Compared to Terrific
      Broth and ZYM-5052 autoinduction medium, the EnBase system improved yield mainly
      through increased productivity per cell. Four-fold increase in oxygen transfer by
      the Ultra Yield Flask contributed to higher cell density with EnBase but not with
      the other tested media, and consequently the product yield per ml of EnBase
      culture was further improved.

PMID- 22152006
TI  - Elevated salivary C-reactive protein levels are associated with active and
      passive smoking in healthy youth: A pilot study.
AB  - BACKGROUND: We examined salivary C-reactive protein (CRP) levels in the context
      of tobacco smoke exposure (TSE) in healthy youth. We hypothesized that there
      would be a dose-response relationship between TSE status and salivary CRP levels.
      METHODS: This work is a pilot study (N = 45) for a larger investigation in which
      we aim to validate salivary CRP against serum CRP, the gold standard measurement
      of low-grade inflammation. Participants were healthy youth with no self-reported
      periodontal disease, no objectively measured obesity/adiposity, and no clinical
      depression, based on the Beck Depression Inventory (BDI-II). We assessed tobacco
      smoking and confirmed smoking status (non-smoking, passive smoking, and active
      smoking) with salivary cotinine measurement. We measured salivary CRP by the
      ELISA method. We controlled for several potential confounders. RESULTS: We found
      evidence for the existence of a dose-response relationship between the TSE status
      and salivary CRP levels. CONCLUSIONS: Our preliminary findings indicate that
      salivary CRP seems to have a similar relation to TSE as its widely used serum
      (systemic inflammatory) biomarker counterpart.

PMID- 22152007
TI  - Predicting failure to return to work.
AB  - AIM: The research question is: is it possible to predict, at the time of workers'
      compensation claim lodgement, which workers will have a prolonged return to work
      (RTW) outcome? This paper illustrates how a traditional analytic approach to the
      analysis of an existing large database can be insufficient to answer the research
      question, and suggests an alternative data management and analysis approach.
      METHODS: This paper retrospectively analyses 9018 workers' compensation claims
      from two different workers' compensation jurisdictions in Australia (two data
      sets) over a 4-month period in 2007. De-identified data, submitted at the time of
      claim lodgement, were compared with RTW outcomes for up to 3 months. Analysis
      consisted of descriptive, parametric (analysis of variance and multiple
      regression), survival (proportional hazards) and data mining (partitioning)
      analysis. RESULTS: No significant associations were found on parametric analysis.
      Multiple associations were found between the predictor variables and RTW outcome
      on survival analysis, with marked differences being found between some sub-groups
      on partitioning--where diagnosis was found to be the strongest discriminator
      (particularly neck and shoulder injuries). There was a consistent trend for
      female gender to be associated with a prolonged RTW outcome. The supplied data
      were not sufficient to enable the development of a predictive model. CONCLUSION:
      If we want to predict early who will have a prolonged RTW in Australia, workers'
      compensation claim forms should be redesigned, data management improved and
      specialised analytic techniques used.

PMID- 22152008
TI  - A common reference population from four European Holstein populations increases
      reliability of genomic predictions.
AB  - BACKGROUND: Size of the reference population and reliability of phenotypes are
      crucial factors influencing the reliability of genomic predictions. It is
      therefore useful to combine closely related populations. Increased accuracies of
      genomic predictions depend on the number of individuals added to the reference
      population, the reliability of their phenotypes, and the relatedness of the
      populations that are combined. METHODS: This paper assesses the increase in
      reliability achieved when combining four Holstein reference populations of 4000
      bulls each, from European breeding organizations, i.e. UNCEIA (France),
      VikingGenetics (Denmark, Sweden, Finland), DHV-VIT (Germany) and CRV (The
      Netherlands, Flanders). Each partner validated its own bulls using their national
      reference data and the combined data, respectively. RESULTS: Combining the data
      significantly increased the reliability of genomic predictions for bulls in all
      four populations. Reliabilities increased by 10%, compared to reliabilities
      obtained with national reference populations alone, when they were averaged over
      countries and the traits evaluated. For different traits and countries, the
      increase in reliability ranged from 2% to 19%. CONCLUSIONS: Genomic selection
      programs benefit greatly from combining data from several closely related
      populations into a single large reference population.

PMID- 22152009
TI  - Protection against Mycobacterium tuberculosis challenge in mice by DNA vaccine
      Ag85A-ESAT-6-IL-21 priming and BCG boosting.
AB  - Tuberculosis (TB) is one of most important chronic infectious diseases caused by
      Mycobacterium tuberculosis and remains a major global health problem. In the
      study, we developed the DNA vaccine encoding fusion protein of antigen 85 A and 6
      kDa early secretory antigen target of M. tuberculosis as well as the cytokine IL
      21 to investigate its immune protective efficacy against M. tuberculosis
      challenge in mice after the DNA vaccine priming and Bacille Calmette-Guerin (BCG)
      boosting. Compared with the different control groups, the intranasal DNA vaccine
      priming twice and BCG boosting once markedly increased the cytotoxicities of
      natural killer cells and splenocytes and enhanced the interferon-gamma level in
      the splenocyte supernatant as well as sIgA level in bronchoalveolar lavage in the
      vaccinated mice. Importantly, this heterologous prime-boost strategy
      significantly decreased the bacterial load in the mouse lungs in contrast to that
      of intranasal or subcutaneous BCG immunization alone. These findings provide
      further approaches for mucosal-targeted prime-boost vaccination to fight against
      TB.

PMID- 22152011
TI  - IUFRO Tree Biotechnology Conference 2011: From Genomes to Integration and
      Delivery Arraial d'Ajuda, Bahia, Brazil.  26 June - 2 July 2011. Abstracts.

PMID- 22152010
TI  - Resistance to topoisomerase cleavage complex induced lethality in Escherichia
      coli via titration of transcription regulators PurR and FNR.
AB  - BACKGROUND: Accumulation of gyrase cleavage complex in Escherichia coli from the
      action of quinolone antibiotics induces an oxidative damage cell death pathway.
      The oxidative cell death pathway has also been shown to be involved in the
      lethality following accumulation of cleavage complex formed by bacterial
      topoisomerase I with mutations that result in defective DNA religation. METHODS:
      A high copy number plasmid clone spanning the upp-purMN region was isolated from
      screening of an E. coli genomic library and analyzed for conferring increased
      survival rates following accumulation of mutant topoisomerase I proteins as well
      as treatment with the gyrase inhibitor norfloxacin. RESULTS: Analysis of the
      intergenic region upstream of purM demonstrated a novel mechanism of resistance
      to the covalent protein-DNA cleavage complex through titration of the cellular
      transcription regulators FNR and PurR responsible for oxygen sensing and
      repression of purine nucleotide synthesis respectively. Addition of adenine to
      defined growth medium had similar protective effect for survival following
      accumulation of topoisomerase cleavage complex, suggesting that increase in
      purine level can protect against cell death. CONCLUSIONS: Perturbation of the
      global regulator FNR and PurR functions as well as increase in purine nucleotide
      availability could affect the oxidative damage cell death pathway initiated by
      topoisomerase cleavage complex.

PMID- 22152012
TI  - Obesity related eating behaviour patterns in Swedish preschool children and
      association with age, gender, relative weight and parental weight--factorial
      validation of the Children's Eating Behaviour Questionnaire.
AB  - BACKGROUND: The Children's Eating Behaviour Questionnaire (CEBQ) is a multi
      dimensional, parent-reported questionnaire measuring children's eating behaviours
      related to obesity risk, i.e. 'enjoyment of food', 'food responsiveness',
      'slowness in eating' and 'satiety responsiveness'. It has not previously been
      validated in a Swedish population, neither on children under the age of 2 years.
      In the present study we examined the factor structure and the reliability of the
      Swedish version of the CEBQ, for use in an obesity intervention programme
      targeting preschool children 1-6 years. Further, the associations between eating
      behaviours and children's age, gender and relative weight (BMI SDS) and parental
      weight were investigated. METHODS: Parents to 174 children aged 1-6 years (50%
      girls, mean age 3.8 years), recruited from five kindergartens in Stockholm,
      completed the Swedish version of the CEBQ. Data on children's weight and height,
      parental weight, height and educational level was collected. Children's relative
      weight was calculated for a subpopulation (mean BMI SDS -0.4, n = 47). Factorial
      validation (Principal Component Analysis) on all CEBQ items was performed.
      Differences in eating behaviours by age, gender and parental weight were
      examined. Correlations between eating behaviours and the child's BMI SDS were
      analysed controlling for age, gender, parental weight and education in linear
      regression analyses. RESULTS: The factor analysis revealed a seven factor
      solution with good psychometric properties, similar to the original structure.
      The behaviour scales 'overeating'/'food responsiveness', 'enjoyment of food' and
      'emotional undereating' decreased with age and 'food fussiness' increased with
      age. Eating behaviours did not differ between girls and boys. The children's
      relative weight was not related to any of the eating behaviours when controlling
      for age, gender, parental weight and education, and only associated with parental
      weight status. CONCLUSIONS: Our results support the use of the CEBQ as a
      psychometric instrument for assessing children's eating behaviours in Swedish
      children aged 1-6 years. Measuring obesity related eating behaviours in
      longitudinal and interventional studies would offer opportunities for studying
      causal effects of eating behaviours in the development of obesity in children.

PMID- 22152013
TI  - Association between high-dose erythropoiesis-stimulating agents, inflammatory
      biomarkers, and soluble erythropoietin receptors.
AB  - BACKGROUND: High-dose erythropoiesis-stimulating agents (ESA) for anemia of
      chronic kidney disease (CKD) have been associated with adverse clinical outcomes
      and do not always improve erythropoiesis. We hypothesized that high-dose ESA
      requirement would be associated with elevated inflammatory biomarkers, decreased
      adipokines, and increased circulating, endogenous soluble erythropoietin
      receptors (sEpoR). METHODS: A cross-sectional cohort of anemic 32 CKD
      participants receiving ESA were enrolled at a single center and cytokine
      profiles, adipokines, and sEpoR were compared between participants stratified by
      ESA dose requirement (usual-dose darbepoetin-alpha (< 1 MUg/kg/week) and high
      dose (>= 1 MUg/kg/week)). RESULTS: Baseline characteristics were similar between
      groups; however, hemoglobin was lower among participants on high-dose (1.4
      MUg/kg/week) vs usual-dose (0.5 MUg/kg/week) ESA.In adjusted analyses, high-dose
      ESA was associated with an increased odds for elevations in c-reactive protein
      and interleukin-6 (p < 0.05 for both). There was no correlation between high-dose
      ESA and adipokines. Higher ESA dose correlated with higher levels of sEpoR (rs =
      0.39, p = 0.03). In adjusted analyses, higher ESA dose (per MUcg/kg/week) was
      associated with a 53% greater odds of sEpoR being above the median (p < 0.05).
      CONCLUSION: High-dose ESA requirement among anemic CKD participants was
      associated with elevated inflammatory biomarkers and higher levels of circulating
      sEpoR, an inhibitor of erythropoiesis. Further research confirming these findings
      is warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT00526747.

PMID- 22152014
TI  - Toxicokinetics of mercury in blood compartments and hair of fish-fed sled dogs.
AB  - BACKGROUND: Understanding mercury (Hg) distribution in blood and the importance
      of hair as an excretory pathway is critical for evaluating risk from long term
      dietary Hg exposure. The major objective of this study was to characterize
      changes in total Hg concentrations in specific blood compartments and hair over
      time due to long term piscivory. METHODS: Eight sled dogs (Canis lupus
      familiaris) were fed either a fish and kibble diet (n = 4), or a fish-free
      control diet (n = 4) for 12 weeks. Concentrations of Hg were monitored throughout
      the exposure period, and for 10 weeks post exposure, until Hg concentrations in
      all blood compartments of one of the exposed dogs dropped below detection limit.
      Additionally, foreleg hair was sampled during acclimation and weeks 0 and 12.
      RESULTS: Hg was detected primarily in whole blood and packed cells, although it
      was sporadically detected at low concentrations in plasma and serum in two of the
      fish fed dogs. Dogs ingested an estimated average of 13.4 +/- 0.58 MUg Hg per kg
      body weight per day. Hg was detectable in whole blood and packed cells within a
      week of exposure. Detected concentrations continued to rise until plateauing at
      approximately 3-6 weeks of exposure at a mean of 9.2 +/- 1.97 ng/g (ppb) in whole
      blood. Hg concentration decreased post exposure following 1st order elimination.
      The mean half-life (t1/2) in whole blood for Hg was 7 weeks. Mean Hg in hair for
      the fish-fed dogs at week 12 was 540 +/- 111 ppb and was significantly greater
      (about 7-fold) than the Hg hair concentration for the control dogs. The hair to
      blood ratio for Hg in fish-fed dogs was 59.0 +/- 7.6:1. CONCLUSIONS: This study
      found the sled dog model to be an effective method for investigating and
      characterizing blood Hg distribution (whole blood, serum, plasma, packed cells)
      and toxicokinetics associated with a piscivorous diet, especially for Hg-exposed
      fur bearing mammals (such as polar bears). Although hair excretion and hair to
      blood Hg ratios were not similar to human concentrations and ratios, the sled dog
      toxicokinetics of Hg in blood, was more similar to that of humans than
      traditional laboratory animals (such as the rat).

PMID- 22152015
TI  - A high-performance quantum dot superluminescent diode with a two-section
      structure.
AB  - Based on InAs/GaAs quantum dots [QDs], a high-power and broadband
      superluminescent diode [SLD] is achieved by monolithically integrating a
      conventional SLD with a semiconductor optical amplifier. The two-section QD-SLD
      device exhibits a high output power above 500 mW with a broad emission spectrum
      of 86 nm. By properly controlling the current injection in the two sections of
      the QD-SLD device, the output power of the SLD can be tuned over a wide range
      from 200 to 500 mW while preserving a broad emission spectrum based on the
      balance between the ground state emission and the first excited state emission of
      QDs. The gain process of the two-section QD-SLD with different pumping levels in
      the two sections is investigated.

PMID- 22152016
TI  - Opposing roles of CXCR4 and CXCR7 in breast cancer metastasis.
AB  - INTRODUCTION: CXCL12-CXCR4 signaling has been shown to play a role in breast
      cancer progression by enhancing tumor growth, angiogenesis, triggering cancer
      cell invasion in vitro, and guiding cancer cells to their sites of metastasis.
      However, CXCR7 also binds to CXCL12 and has been recently found to enhance lung
      and breast primary tumor growth, as well as metastasis formation. Our goal was to
      dissect the contributions of CXCR4 and CXCR7 to the different steps of metastasis
      - in vivo invasion, intravasation and metastasis formation. METHODS: We
      overexpressed CXCR4, CXCR7 or both in the rat mammary adenocarcinoma cell line
      MTLn3. Stable expressors were used to form tumors in severe combined
      immunodeficiency (SCID) mice, and in vivo invasiveness, intravital motility,
      intravasation, and metastasis were measured. RESULTS: We found that CXCR4
      overexpression increased the chemotactic and invasive behavior of MTLn3 cells to
      CXCL12, both in vitro and in vivo, as well as in vivo motility and intravasation.
      CXCR7 overexpression enhanced primary tumor growth and angiogenesis (as indicated
      by microvessel density and VEGFA expression), but decreased in vivo invasion,
      intravasation, and metastasis formation. In vitro, expression of CXCR7 alone had
      no effect in chemotaxis or invasion to CXCL12. However, in the context of
      increased CXCR4 expression, CXCR7 enhanced chemotaxis to CXCL12 but decreased
      invasion in response to CXCL12 in vitro and in vivo and impaired CXCL12
      stimulated matrix degradation. The changes in matrix degradation correlated with
      expression of matrix metalloproteinase 12 (MMP12). CONCLUSIONS: We find that
      CXCR4 and CXCR7 play different roles in metastasis, with CXCR4 mediating breast
      cancer invasion and CXCR7 impairing invasion but enhancing primary tumor growth
      through angiogenesis.

PMID- 22152017
TI  - Distal and proximal family predictors of adolescents' smoking initiation and
      development: a longitudinal latent curve model analysis.
AB  - BACKGROUND: Studies on adolescent smoking indicate that the smoking behaviours of
      their parents, siblings and friends are significant micro-level predictors.
      Parents' socioeconomic status (SES) is an important macro-level predictor. We
      examined the longitudinal relationships between these predictors and the
      initiation and development of adolescents' smoking behaviour in Norway. METHODS:
      We employed data from The Norwegian Longitudinal Health Behaviour Study (NLHB),
      in which participants were followed from the age of 13 to 30. We analysed data
      from the first 5 waves, covering the age span from 13 to 18, with latent curve
      modeling (LCM). RESULTS: Smoking rates increased from 3% to 31% from age 13 to
      age 18. Participants' smoking was strongly associated with their best friends'
      smoking. Parental SES, parents' smoking and older siblings' smoking predicted
      adolescents' initial level of smoking. Furthermore, the same variables predicted
      the development of smoking behaviour from age 13 to 18. Parents' and siblings'
      smoking behaviours acted as mediators of parents' SES on the smoking habits of
      adolescents. CONCLUSIONS: Parents' SES was significantly associated, directly and
      indirectly, with both smoking initiation and development. Parental and older
      siblings' smoking behaviours were positively associated with both initiation and
      development of smoking behaviour in adolescents. There were no significant gender
      differences in these associations.

PMID- 22152019
TI  - Characterization of the ileal microbiota in rejecting and nonrejecting recipients
      of small bowel transplants.
AB  - Small bowel transplantation can be a life-preserving procedure for patients with
      irreversible intestinal failure. Allograft rejection remains a major source of
      morbidity and mortality and its accurate diagnosis and treatment are critical. In
      this study, we used pyrosequencing of 16S ribosomal RNA gene tags to compare the
      composition of the ileal microbiota present during nonrejection, prerejection and
      active rejection states in small bowel transplant patients. During episodes of
      rejection, the proportions of phylum Firmicutes (p < 0.001) and the order
      Lactobacillales (p < 0.01) were significantly decreased, while those of the
      phylum Proteobacteria, especially the family Enterobacteriaceae, were
      significantly increased (p < 0.005). Receiver-operating characteristic analysis
      revealed that relative proportions of several bacterial taxa in ileal effluents
      and especially Firmicutes, could be used to discriminate between nonrejection and
      active rejection. In conclusion, the findings obtained during this study suggest
      that small bowel transplant rejection is associated with changes in the microbial
      populations in ileal effluents and support microbiota profiling as a potential
      diagnostic biomarker of rejection. Future studies should investigate if the
      dysbiosis that we observed is a cause or a consequence of the rejection process.

PMID- 22152020
TI  - Caveolin 1 protein expression in renal cell carcinoma predicts survival.
AB  - BACKGROUND: Caveolae play a significant role in disease phenotypes such as
      cancer, diabetes, bladder dysfunction, and muscular dystrophy. The aim of this
      study was to elucidate the caveolin-1 (CAV1) protein expression in renal cell
      cancer (RCC) and to determine its potential prognostic relevance. METHODS: 289
      clear cell RCC tissue specimens were collected from patients undergoing surgery
      for renal tumors. Both cytoplasmic and membranous CAV1 expression were determined
      by immunohistochemistry and correlated with clinical variables. Survival analysis
      was carried out for 169 evaluable patients with a median follow up of 80.5 months
      (interquartile range (IQR), 24.5-131.7 months). RESULTS: A high CAV1 expression
      in the tumor cell cytoplasm was significantly associated with male sex (p =
      0.04), a positive nodal status (p = 0.04), and poor tumor differentiation (p =
      0.04). In contrast, a higher than average (i.e. > median) CAV1 expression in
      tumor cell membranes was only linked to male sex (p = 0.03). Kaplan-Meier
      analysis disclosed significant differences in 5-year overall (51.4 vs. 75.2%, p =
      0.001) and tumor specific survival (55.3 vs. 80.1%, p = 0.001) for patients with
      higher and lower than average cytoplasmic CAV1 expression levels, respectively.
      Applying multivariable Cox regression analysis a high CAV1 protein expression
      level in the tumor cell cytoplasm could be identified as an independent poor
      prognostic marker of both overall (p = 0.02) and tumor specific survival (p =
      0.03) in clear cell RCC patients. CONCLUSION: Over expression of caveolin-1 in
      the tumour cell cytoplasm predicts a poor prognosis of patients with clear cell
      RCC. CAV1 is likely to be a useful prognostic marker and may play an important
      role in tumour progression. Therefore, our data encourage further investigations
      to enlighten the role of CAV1 and its function as diagnostic and prognostic
      marker in serum and/or urine of RCC patients.

PMID- 22152021
TI  - Soft tagging of overlapping high confidence gene mention variants for cross
      species full-text gene normalization.
AB  - BACKGROUND: Previously, gene normalization (GN) systems are mostly focused on
      disambiguation using contextual information. An effective gene mention tagger is
      deemed unnecessary because the subsequent steps will filter out false positives
      and high recall is sufficient. However, unlike similar tasks in the past
      BioCreative challenges, the BioCreative III GN task is particularly challenging
      because it is not species-specific. Required to process full-length articles, an
      ineffective gene mention tagger may produce a huge number of ambiguous false
      positives that overwhelm subsequent filtering steps while still missing many true
      positives. RESULTS: We present our GN system participated in the BioCreative III
      GN task. Our system applies a typical 2-stage approach to GN but features a soft
      tagging gene mention tagger that generates a set of overlapping gene mention
      variants with a nearly perfect recall. The overlapping gene mention variants
      increase the chance of precise match in the dictionary and alleviate the need of
      disambiguation. Our GN system achieved a precision of 0.9 (F-score 0.63) on the
      BioCreative III GN test corpus with the silver annotation of 507 articles. Its
      TAP-k scores are competitive to the best results among all participants.
      CONCLUSIONS: We show that despite the lack of clever disambiguation in our gene
      normalization system, effective soft tagging of gene mention variants can indeed
      contribute to performance in cross-species and full-text gene normalization.

PMID- 22152022
TI  - MyChemise: A 2D drawing program that uses morphing for visualisation purposes.
AB  - MyChemise (My Chemical Structure Editor) is a new 2D structure editor. It is
      designed as a Java applet that enables the direct creation of structures in the
      Internet using a web browser. MyChemise saves files in a digital format (.cse)
      and the import and export of .mol files using the appropriate connection tables
      is also possible.MyChemise is available as a free online version in English and
      German. The MyChemise GUI is designed to be user friendly and can be used
      intuitively. There is also an English and German program description available as
      a PDF file.In addition to the known ways of drawing chemical structure formulas,
      there are also parts implemented in the program that allow the creation of
      different types of presentation. The morphing module uses this technology as a
      component for dynamic visualisation. For example, it enables a clear and simple
      illustration of molecule vibrations and reaction sequences.

PMID- 22152023
TI  - Unusual presentation of hepatitis B serological markers in an Amerindian
      community of Venezuela with a majority of occult cases.
AB  - BACKGROUND: Occult hepatitis B infection (OBI) is characterized by the presence
      of hepatitis B virus (HBV) DNA in the absence of HBsAg in the serum of patients.
      The aim of this study was to characterize HBV infection among a Piaroa community,
      an Amerindian group which exhibits significant evidence of exposure to HBV but
      relatively low presence of HBsAg, and to explore the presence of OBI in this
      population. RESULTS: Of 150 sera, with 17% anti-HBc and 1.3% HBsAg prevalence, 70
      were tested for the presence of HBV DNA. From these, 25 (36%) were found positive
      for HBV DNA by PCR in the core region. Two of these 25 sera were HBsAg positive,
      indicating an overt infection. Of the remaining 68 sera tested, 23 exhibited OBI.
      Of these, 13 were HBV DNA out of 25 anti-HBc positive (52%) and 10 HBV DNA
      positive, out of 43 anti-HBc negative (23%), with a statistical significance of p
      = 0.03. Viral DNA and HBsAg were present intermittently in follow up sera of 13
      individuals. Sequence analysis in the core region of the amplified DNA products
      showed that all the strains belonged to HBV genotype F3. The OBI isolates
      displayed 96-100% nucleotide identity between them. One isolate exhibited the co
      circulation of a wild type variant with a variant with a premature stop codon at
      the core protein, and a variant exhibiting a deletion of 28 amino acids.
      CONCLUSIONS: The frequency of OBI found in this Amerindian group warrants further
      studies in other communities exhibiting different degrees of HBV exposure.

PMID- 22152024
TI  - Vitreous inflammatory factors and serous retinal detachment in central retinal
      vein occlusion: a case control series.
AB  - BACKGROUND: This study investigated whether the vitreous fluid levels of soluble
      vascular endothelial growth factor receptor-2 (sVEGFR-2), pigment epithelium
      derived factor (PEDF), and soluble intercellular adhesion molecule 1 (sICAM-1)
      were associated with the occurrence of serous retinal detachment (SRD) in
      patients with central retinal vein occlusion (CRVO). METHODS: We recruited 33
      patients with CRVO and macular edema, as well as 18 controls with nonischemic
      ocular diseases. Eighteen of the 33 patients with CRVO showed SRD on optical
      coherence tomography of the macula (defined as subretinal accumulation of fluid
      with low reflectivity), while the other 15 patients only had cystoid macular
      edema (CME, defined as hyporeflective intraretinal cavities). Retinal ischemia
      was evaluated by measuring the area of capillary non-perfusion using fluorescein
      angiography and the public domain Scion Image program, while central macular
      thickness (CMT) was examined by optical coherence tomography. Vitreous fluid
      samples were obtained during pars plana vitrectomy and levels of the target
      molecules were measured by enzyme-linked immunosorbent assay. RESULTS: Ischemia
      was significantly more common in the SRD group (17/18 patients) than in the CME
      group (5/15 patients) (P < 0.001). The vitreous fluid level of sICAM-1 increased
      significantly across the three groups from the control group (4.98 +/- 1.73
      ng/ml) to the CME group (15.4 +/- 10.1 ng/ml) and the SRD group (27.1 +/- 17.7
      ng/ml) (ptrend< 0.001). The vitreous fluid level of sVEGFR-2 also showed a
      significant increase across the three groups (1083 +/- 541 pg/ml, 1181 +/- 522
      pg/ml, and 1535 +/- 617 pg/ml, respectively, ptrend = 0.019). On the other hand,
      the vitreous fluid level of PEDF showed a significant decrease across the three
      groups (56.4 +/- 40.0 ng/ml, 24.3 +/- 17.3 ng/ml, and 16.4 +/- 12.6 ng/ml,
      respectively, ptrend< 0.001). CONCLUSIONS: Higher levels of inflammatory factors
      (sICAM-1 and sVEGFR-2) and lower levels of anti-inflammatory PEDF were observed
      in macular edema patients with SRD, suggesting that inflammation plays a key role
      in determining the severity of CRVO.

PMID- 22152025
TI  - Plasmacytoid myoepithelioma of minor salivary glands: report of case with
      emphasis in the immunohistochemical findings.
AB  - Myoepithelioma is a rare benign tumor of the salivary glands and is usually seen
      in the parotid gland and the minor salivary glands. It was once considered to be
      a type of pleomorphic adenoma (PA), but myoepitheliomas are today believed to be
      relatively aggressive tumors. Myoepitheliomas are most common in young adults
      between the ages of 30 and 50 and there are very few cases reported in
      individuals less than 18 years of age. We report a case of myoepithelioma located
      in the hard palate in a 15-year-old Brazilian male. The tumor was composed of
      plasmacytoid myoepithelial cells. An analysis of the immunohistochemical profile
      of the tumor cells showed positivity for vimentin, S-100 protein, and glial
      fibrillary acidic protein (GFAP), but not for smooth muscle actin (alpha-SMA) and
      cytokeratin 14 (CK14). We report this case because of the rarity of this tumor,
      especially in adolescents. We also discuss the histological parameters of the
      differential diagnosis of this tumor as well as its immunohistochemical profile.

PMID- 22152026
TI  - Low-dose ionising radiation from medical imaging in patients hospitalised in
      Internal Medicine.
AB  - BACKGROUND: Medical imaging is responsible for increasing exposure to low-dose
      ionising radiation in the general population. The extent of exposure in specific
      patient populations remains to be determined. AIM: We sought to determine the
      level of exposure in patients hospitalised in General Internal Medicine. METHODS:
      In this retrospective cohort study, we searched the Centre Informatise de
      Recherche Evaluative en Services et Soins de Sante database for adult patients
      hospitalised in General Internal Medicine from 1 January 2008 to 31 December
      2008. We collected data on demographics, co-morbidities, and radiological and
      nuclear imaging. We used data from the literature to calculate an estimated
      annual effective dose for each patient and searched for factors associated with
      higher exposure. RESULTS: One thousand one hundred eighty-seven (1187) patients
      were hospitalised at least once during the study period. The median age was 69
      years (interquartile range 56-81) and 636 (53.6%) were men. The median annual
      effective dose of the whole cohort was 8.7 mSv/year. Patients aged between 55 and
      80 years were exposed to a higher median effective dose compared with their
      younger and older counterparts (P < 0.001). Patients with cardiac, pulmonary,
      peripheral arterial and neoplastic disease were at higher risk of exposure to
      high and very high annual effective dose (P < 0.01). Patients with longer
      hospitalisations were at higher risk of exposure to high and very high annual
      effective dose (P < 0.01). CONCLUSION: Patients hospitalised on a General
      Internal Medicine ward are exposed to three times more ionising radiation than
      the general population.

PMID- 22152027
TI  - Genetic variants in IFIH1 play opposite roles in the pathogenesis of psoriasis
      and chronic periodontitis.
AB  - The IFIH1 gene is a key factor connecting environmental and genetic factors in
      the pathogenesis of immune-related diseases. We aimed to investigate whether it
      has effects on psoriasis, chronic periodontitis and skin test-positive penicillin
      allergy and to confirm whether these diseases have shared molecular mechanisms
      originating from shared genetics. Two common variants in IFIH1 were genotyped in
      561 patients with psoriasis, 421 patients with chronic periodontitis, 175
      patients with skin test-positive penicillin allergy and 1100 shared controls.
      Then, case-control study was used to analyse the association between IFIH1 and
      the three diseases. The allele distributions of rs1990760 and rs3747517 in the
      Chinese population are much different from the European population. The A allele
      of rs1990760 (OR = 1.30, P = 5.4 * 10(-3)) and A-G (rs1990760/rs3747517)
      haplotype (OR = 1.31, P = 3.8 * 10(-3)) were highly associated with the risk of
      psoriasis. However, the A allele of rs1990760 (OR = 0.73, P = 7.8 * 10(-3)) and A
      G haplotype (OR = 0.71, P = 4.5 * 10(-3)) were identified as protective factors
      for chronic periodontitis. IFIH1 affects several immune-related diseases,
      including psoriasis and chronic periodontitis, and provides a molecular link
      between genetic susceptibility, viral infections and immune-related diseases.
      Moreover, we also confirm the hypothesis that shared molecular mechanisms from
      common genetic variants contribute to a spectrum of immune-related diseases.

PMID- 22152028
TI  - In vitro effects of 2-methoxyestradiol-bis-sulphamate on reactive oxygen species
      and possible apoptosis induction in a breast adenocarcinoma cell line.
AB  - BACKGROUND: In the search for anticancer agents, a promising 17-beta-estradiol
      metabolite, 2-methoxyestradiol (2ME2) was found that exerts antiproliferative in
      vitro and in vivo activity. Since 2ME2 has limited biological accessibility and
      rapid metabolic degradation, the purpose of this study was to investigate the in
      vitro influence exerted by an analogue of 2ME2 namely 2-methoxyestradiol-bis
      sulphamate (2MEBM) in a breast adenocarcinoma cell line (MCF-7). METHODS: This
      was conducted by investigating 2MEBM's in vitro influence on cell cycle
      progression, mitochondrial membrane potential and possible production of reactive
      oxygen species (ROS) generation. In vitro effects of 2MEBM on cell cycle
      progression was demonstrated by means of flow cytometry using propidium iodide.
      Hydrogen peroxide and superoxide production was investigated using 2,7
      dichlorofluorescein diacetate and hydroethidine, respectively. The probable
      reduction in the mitochondrial membrane potential was demonstrated using a
      MitoCaptureTM kit. RESULTS: Cell cycle progression revealed the presence of a sub
      G1 apoptotic peak. Reduction of mitochondrial membrane potential after exposure
      to 2MEBM was demonstrated and an increase in ROS production was also observed.
      CONCLUSION: This study verified that 2MEBM exposure resulted in apoptosis
      induction, increased ROS production and reduced mitochondrial membrane potential
      in a tumorigenic breast epithelial cell line. Data obtained from this project
      contributes to the unravelling of the in vitro signal transduction of 2MEBM in
      tumorigenic cell lines.

PMID- 22152029
TI  - Evolution of orthologous tandemly arrayed gene clusters.
AB  - BACKGROUND: Tandemly Arrayed Gene (TAG) clusters are groups of paralogous genes
      that are found adjacent on a chromosome. TAGs represent an important repertoire
      of genes in eukaryotes. In addition to tandem duplication events, TAG clusters
      are affected during their evolution by other mechanisms, such as inversion and
      deletion events, that affect the order and orientation of genes. The DILTAG
      algorithm developed in 1 makes it possible to infer a set of optimal evolutionary
      histories explaining the evolution of a single TAG cluster, from an ancestral
      single gene, through tandem duplications (simple or multiple, direct or
      inverted), deletions and inversion events. RESULTS: We present a general
      methodology, which is an extension of DILTAG, for the study of the evolutionary
      history of a set of orthologous TAG clusters in multiple species. In addition to
      the speciation events reflected by the phylogenetic tree of the considered
      species, the evolutionary events that are taken into account are simple or
      multiple tandem duplications, direct or inverted, simple or multiple deletions,
      and inversions. We analysed the performance of our algorithm on simulated data
      sets and we applied it to the protocadherin gene clusters of human, chimpanzee,
      mouse and rat. CONCLUSIONS: Our results obtained on simulated data sets showed a
      good performance in inferring the total number and size distribution of
      duplication events. A limitation of the algorithm is however in dealing with
      multiple gene deletions, as the algorithm is highly exponential in this case, and
      becomes quickly intractable.

PMID- 22152030
TI  - Chemotherapy-induced cognitive impairment is associated with decreases in cell
      proliferation and histone modifications.
AB  - BACKGROUND: In this study, we examined the effects of cyclophosphamide,
      methothrexate, and 5-Fluorouracil (CMF) drug combination on various aspects of
      learning and memory. We also examined the effects of CMF on cell proliferation
      and chromatin remodeling as possible underlying mechanisms to explain
      chemotherapy-associated cognitive dysfunction. Twenty-four adult female Wistar
      rats were included in the study and had minimitter implantation for continuous
      activity monitoring two weeks before the chemotherapy regimen was started. Once
      baseline activity data were collected, rats were randomly assigned to receive
      either CMF or saline injections given intraperitoneally. Treatments were given
      once a week for a total of 4 weeks. Two weeks after the last injection, rats were
      tested in the water maze for spatial learning and memory ability as well as
      discrimination learning. Bromodeoxyuridine (BrdU) injection was given at 100
      mg/Kg intraperitoneally 4 hours prior to euthanasia to determine hippocampal cell
      proliferation while histone acetylation and histone deacetylase activity was
      measured to determine CMF effects on chromatin remodeling. RESULTS: Our data
      showed learning and memory impairment following CMF administration independent of
      the drug effects on physical activity. In addition, CMF-treated rats showed
      decreased hippocampal cell proliferation, associated with increased histone
      acetylation and decreased histone deacetylase activity. CONCLUSIONS: These
      results suggest the negative consequences of chemotherapy on brain function and
      that anti-cancer drugs can adversely affect the self-renewal potential of neural
      progenitor cells and also chromatin remodeling in the hippocampus. The
      significance of our findings lie on the possible usefulness of animal models in
      addressing the clinical phenomenon of 'chemobrain.'

PMID- 22152032
TI  - Cross-linking cellulose nanofibrils for potential elastic cryo-structured gels.
AB  - Cellulose nanofibrils were produced from P. radiata kraft pulp fibers. The
      nanofibrillation was facilitated by applying 2,2,6,6-tetramethylpiperidinyl-1
      oxyl-mediated oxidation as pretreatment. The oxidized nanofibrils were cross
      linked with polyethyleneimine and poly N-isopropylacrylamide-co-allylamine-co
      methylenebisacrylamide particles and were frozen to form cryo-structured gels.
      Samples of the gels were critical-point dried, and the corresponding structures
      were assessed with scanning electron microscopy. It appears that the aldehyde
      groups in the oxidized nanofibrils are suitable reaction sites for cross-linking.
      The cryo-structured materials were spongy, elastic, and thus capable of regaining
      their shape after a given pressure was released, indicating a successful cross
      linking. These novel types of gels are considered potential candidates in
      biomedical and biotechnological applications.

PMID- 22152031
TI  - Year in review 2010: Critical Care--Infection.
AB  - Infections remain among the most important concerns in critically ill patients.
      Early and reliable diagnosis of infection still poses difficulties in this
      setting but also represents a crucial step toward appropriate antimicrobial
      therapy. Increasing antimicrobial resistance challenges established approaches to
      the optimal management of infections in the intensive care unit. Rapid infection
      diagnosis, antibiotic dosing and optimization through pharmacologic indices,
      progress in the implementation of effective antimicrobial stewardship and
      infection control programs, and management of fungal infections are some of the
      most relevant issues in this special patient population. During the last 18
      months, Critical Care and other journals have provided a wide array of
      descriptive and interventional clinical studies and scientific reports helping
      clinical investigators and critical care physicians to improve diagnosis,
      management, and therapy of infections in critically ill patients.

PMID- 22152033
TI  - A cobalt complex of a microbial arene oxidation product.
AB  - We report the first synthesis of a cobalt Cp diene complex wherein the diene is
      derived by microbial dearomatising dihydroxylation of an aromatic ring. The
      complex has been characterised crystallographically and its structure is compared
      to that of an uncomplexed diene precursor.

PMID- 22152034
TI  - Identification of candidate genes for yeast engineering to improve bioethanol
      production in very high gravity and lignocellulosic biomass industrial
      fermentations.
AB  - BACKGROUND: The optimization of industrial bioethanol production will depend on
      the rational design and manipulation of industrial strains to improve their
      robustness against the many stress factors affecting their performance during
      very high gravity (VHG) or lignocellulosic fermentations. In this study, a set of
      Saccharomyces cerevisiae genes found, through genome-wide screenings, to confer
      resistance to the simultaneous presence of different relevant stresses were
      identified as required for maximal fermentation performance under industrial
      conditions. RESULTS: Chemogenomics data were used to identify eight genes whose
      expression confers simultaneous resistance to high concentrations of glucose,
      acetic acid and ethanol, chemical stresses relevant for VHG fermentations; and
      eleven genes conferring simultaneous resistance to stresses relevant during
      lignocellulosic fermentations. These eleven genes were identified based on two
      different sets: one with five genes granting simultaneous resistance to ethanol,
      acetic acid and furfural, and the other with six genes providing simultaneous
      resistance to ethanol, acetic acid and vanillin. The expression of Bud31 and Hpr1
      was found to lead to the increase of both ethanol yield and fermentation rate,
      while Pho85, Vrp1 and Ygl024w expression is required for maximal ethanol
      production in VHG fermentations. Five genes, Erg2, Prs3, Rav1, Rpb4 and Vma8,
      were found to contribute to the maintenance of cell viability in wheat straw
      hydrolysate and/or the maximal fermentation rate of this substrate. CONCLUSIONS:
      The identified genes stand as preferential targets for genetic engineering
      manipulation in order to generate more robust industrial strains, able to cope
      with the most significant fermentation stresses and, thus, to increase ethanol
      production rate and final ethanol titers.

PMID- 22152035
TI  - Gender and socioeconomic disparities in BMI trajectories in the Seychelles: a
      cohort analysis based on serial population-based surveys.
AB  - BACKGROUND: The relationship between body mass index (BMI) and socioeconomic
      status (SES) tends to change over time and across populations. In this study, we
      examined, separately in men and women, whether the association between BMI and
      SES changed over successive birth cohorts in the Seychelles (Indian Ocean,
      African region). METHODS: We used data from all participants in three surveys
      conducted in 1989, 1994 and 2004 in independent random samples of the population
      aged 25-64 years in the Seychelles (N = 3'403). We used linear regression to
      model mean BMI according to age, cohort, SES and smoking status, allowing for a
      quadratic term for age to account for a curvilinear relation between BMI and age
      and interactions between SES and age and between SES and cohorts to test whether
      the relation between SES and BMI changed across subsequent cohorts. All analyses
      were performed separately in men and women. RESULTS: BMI increased with age in
      all birth cohorts. BMI was lower in men of low SES than high SES but was higher
      in women of low SES than high SES. In all SES categories, BMI increased over
      successive cohorts (1.24 kg/m2 in men and 1.51 kg/m2 for a 10-year increase in
      birth cohorts, p < 0.001). The difference in BMI between men or women of high vs.
      low SES did not change significantly across successive cohorts (the interaction
      between SES and year of birth of cohort was statistically not significant).
      Smoking was associated with lower BMI in men and women (respectively -1.55 kg/m2
      and 2.46 kg/m2, p < 0.001). CONCLUSIONS: Although large differences exist between
      men and women, social patterning of BMI did not change significantly over
      successive cohorts in this population of a middle-income country in the African
      region.

PMID- 22152036
TI  - An evidence based review of the assessment and management of penetrating neck
      trauma.
AB  - BACKGROUND: Although relatively uncommon, penetrating neck trauma has the
      potential for serious morbidity and an estimated mortality of up to 6%. The
      assessment and management of patients who have sustained a penetrating neck
      injury has historically been an issue surrounded by significant controversy.
      OBJECTIVES OF REVIEW: To assess recent evidence relating to the assessment and
      management of penetrating neck trauma, highlighting areas of controversy with an
      overall aim of formulating clinical guidelines according to a care pathway
      format. TYPE OF REVIEW: Structured, non-systematic review of recent medical
      literature. SEARCH STRATEGY: An electronic literature search was performed in May
      2011. The Medline database was searched using the Medical Subject Headings terms
      'neck injuries' and 'wounds, penetrating' in conjunction with the terms
      'assessment' or 'management'. Embase was searched with the terms 'penetrating
      trauma' and 'neck injury', also in conjunction with the terms 'assessment' and
      'management'. Results were limited to articles published in English from 1990 to
      the present day. EVALUATION METHOD: Abstracts were reviewed by the first three
      authors to select full-text articles for further critical appraisal. The
      references and citation links of these articles were hand-searched to identify
      further articles of relevance. RESULTS: 147 relevant articles were identified by
      the electronic literature search, comprising case series, case reports and
      reviews. 33 were initially selected for further evaluation. CONCLUSIONS: Although
      controversy continues to surround the management of penetrating neck trauma, the
      role of selective non-operative management and the utility of CT angiography to
      investigate potential vascular injuries appears to be increasingly accepted.

PMID- 22152038
TI  - Calorie menu labeling on quick-service restaurant menus: an updated systematic
      review of the literature.
AB  - Nutrition labels are one strategy being used to combat the increasing prevalence
      of overweight and obesity in the United States. The Patient Protection and
      Affordable Care Act of 2010 mandates that calorie labels be added to menu boards
      of chain restaurants with 20 or more locations. This systematic review includes
      seven studies published since the last review on the topic in 2008. Authors
      searched for peer-reviewed studies using PUBMED and Google Scholar. Included
      studies used an experimental or quasi-experimental design comparing a calorie
      labeled menu with a no-calorie menu and were conducted in laboratories, college
      cafeterias, and fast food restaurants. Two of the included studies were judged to
      be of good quality, and five of were judged to be of fair quality. Observational
      studies conducted in cities after implementation of calorie labeling were
      imprecise in their measure of the isolated effects of calorie labels.
      Experimental studies conducted in laboratory settings were difficult to
      generalize to real world behavior. Only two of the seven studies reported a
      statistically significant reduction in calories purchased among consumers using
      calorie-labeled menus. The current evidence suggests that calorie labeling does
      not have the intended effect of decreasing calorie purchasing or consumption.

PMID- 22152037
TI  - Gray matter imaging in multiple sclerosis: what have we learned?
AB  - At the early onset of the 20th century, several studies already reported that the
      gray matter was implicated in the histopathology of multiple sclerosis (MS).
      However, as white matter pathology long received predominant attention in this
      disease, and histological staining techniques for detecting myelin in the gray
      matter were suboptimal, it was not until the beginning of the 21st century that
      the true extent and importance of gray matter pathology in MS was finally
      recognized. Gray matter damage was shown to be frequent and extensive, and more
      pronounced in the progressive disease phases. Several studies subsequently
      demonstrated that the histopathology of gray matter lesions differs from that of
      white matter lesions. Unfortunately, imaging of pathology in gray matter
      structures proved to be difficult, especially when using conventional magnetic
      resonance imaging (MRI) techniques. However, with the recent introduction of
      several more advanced MRI techniques, the detection of cortical and subcortical
      damage in MS has considerably improved. This has important consequences for
      studying the clinical correlates of gray matter damage. In this review, we
      provide an overview of what has been learned about imaging of gray matter damage
      in MS, and offer a brief perspective with regards to future developments in this
      field.

PMID- 22152039
TI  - Photodynamic therapy and end-stage tongue base cancer: short communication.
AB  - We previously reported on the outcome of 21 patients with stage IV advanced
      and/or recurrent tongue base carcinoma subjected to mTHPC-PDT. We continue to
      develop on the previous work by treating more patients with this unforgiving
      disease. PDT has shown to be a very successful minimally-invasive surgical tool
      in managing this pathology. Tumour-associated symptoms were reduced
      significantly. The overall morbidity and mortality following PDT, in this group
      of patients, were far less when compared with other conventional modalities.

PMID- 22152040
TI  - Treatment of upper urinary tract stones with extracorporeal shock wave
      lithotripsy (ESWL) Sonolith vision.
AB  - BACKGROUND: The aim was to retrospectively assess the results of treatment of
      upper urinary tract stones with the Sonolith vision manufactured by EDAP, and
      purchased in 2004. METHODS: The subjects were 226 Japanese patients who underwent
      extracorporeal shock wave lithotripsy (ESWL) alone as an initial treatment and
      could be followed up for at least 3 months, selected from 277 candidate patients
      who underwent this therapy between 2004 and 2006. Treatment effect was evaluated
      by kidney, ureter, and bladder X-ray or renal ultrasonography at 1 and 3 months
      after treatment. A stone-free status or status of stone fragmentation to 4 mm or
      smaller was considered to indicate effective treatment. RESULTS: At 3 months
      after treatment, the stone-free rate was 69.4% and the efficacy rate was 77.4%
      for renal stones, while these rates were 91.5 and 93.3%, respectively for
      ureteral stones. Assessment of treatment effect classified by the location of
      stones revealed a stone-free rate of 94.6% and an efficacy rate of 94.6% for
      lower ureteral stones (4.0 mm or smaller, 1 subject; 4.1-10.0 mm, 31 subjects;
      10.1-20.0 mm, 5 subjects: number of treatment sessions, 1 or 2 sessions [mean:
      1.03 sessions]). Complications of this therapy included renal subcapsular
      hematoma and pyelonephritis in 1 case each. CONCLUSIONS: ESWL with the Sonolith
      vision manufactured by EDAP produced a treatment effect equivalent to those
      achieved with other models of ESWL equipment. ESWL seems to be an effective first
      line treatment also in patients who have lower ureteral stones 10 mm or larger
      but do not wish to undergo TUL, if measures such as suitable positioning of the
      patient during treatment are taken.

PMID- 22152041
TI  - Polymerase activity of hybrid ribonucleoprotein complexes generated from
      reassortment between 2009 pandemic H1N1 and seasonal H3N2 influenza A viruses.
AB  - BACKGROUND: A novel influenza virus (2009 pdmH1N1) was identified in early 2009
      and progressed to a pandemic in mid-2009. This study compared the polymerase
      activity of recombinant viral ribonucleoprotein (vRNP) complexes derived from
      2009 pdmH1N1 and the co-circulating seasonal H3N2, and their possible
      reassortants. RESULTS: The 2009 pdmH1N1 vRNP showed a lower level of polymerase
      activity at 33 degrees C compared to 37 degrees C, a property remenisence of
      avian viruses. The 2009 pdmH1N1 vRNP was found to be more cold-sensitive than the
      WSN or H3N2 vRNP. Substituion of 2009 pdmH1N1 vRNP with H3N2-derived-subunits,
      and vice versa, still retained a substantial level of polymerase activity, which
      is probably compartable with survival. When the 2009 pdmH1N1 vRNP was substituted
      with H3N2 PA, a significant increase in activity was observed; whereas when H3N2
      vRNP was substituted with 2009 pdmH1N1 PA, a significant decrease in activity
      occurred. Although, the polymerase basic protein 2 (PB2) of 2009 pdmH1N1 was
      originated from an avian virus, substitution of this subunit with H3N2 PB2 did
      not change its polymerase activity in human cells. CONCLUSIONS: In conclusion,
      our data suggest that hybrid vRNPs resulted from reassortment between 2009
      pdmH1N1 and H3N2 viruses could still retain a substantial level of polymerase
      activity. Substituion of the subunit PA confers the most prominent effect on
      polymerase activity. Further studies to explore the determinants for polymerase
      activity of influenza viruses in associate with other factors that limit host
      specificity are warrant.

PMID- 22152042
TI  - Cellular oxido-reductive proteins of Chlamydomonas reinhardtii control the
      biosynthesis of silver nanoparticles.
AB  - BACKGROUND: Elucidation of molecular mechanism of silver nanoparticles (SNPs)
      biosynthesis is important to control its size, shape and monodispersity. The
      evaluation of molecular mechanism of biosynthesis of SNPs is of prime importance
      for the commercialization and methodology development for controlling the shape
      and size (uniform distribution) of SNPs. The unicellular algae Chlamydomonas
      reinhardtii was exploited as a model system to elucidate the role of cellular
      proteins in SNPs biosynthesis. RESULTS: The C. reinhardtii cell free extract (in
      vitro) and in vivo cells mediated synthesis of silver nanoparticles reveals SNPs
      of size range 5 +/- 1 to 15 +/- 2 nm and 5 +/- 1 to 35 +/- 5 nm respectively. In
      vivo biosynthesized SNPs were localized in the peripheral cytoplasm and at one
      side of flagella root, the site of pathway of ATP transport and its synthesis
      related enzymes. This provides an evidence for the involvement of oxidoreductive
      proteins in biosynthesis and stabilization of SNPs. Alteration in size
      distribution and decrease of synthesis rate of SNPs in protein-depleted fractions
      confirmed the involvement of cellular proteins in SNPs biosynthesis.
      Spectroscopic and SDS-PAGE analysis indicate the association of various proteins
      on C. reinhardtii mediated in vivo and in vitro biosynthesized SNPs. We have
      identified various cellular proteins associated with biosynthesized (in vivo and
      in vitro) SNPs by using MALDI-MS-MS, like ATP synthase, superoxide dismutase,
      carbonic anhydrase, ferredoxin-NADP+ reductase, histone etc. However, these
      proteins were not associated on the incubation of pre-synthesized silver
      nanoparticles in vitro. CONCLUSION: Present study provides the indication of
      involvement of molecular machinery and various cellular proteins in the
      biosynthesis of silver nanoparticles. In this report, the study is mainly focused
      towards understanding the role of diverse cellular protein in the synthesis and
      capping of silver nanoparticles using C. reinhardtii as a model system.

PMID- 22152043
TI  - Ethnic differences in use values and use patterns of Parkia biglobosa in Northern
      Benin.
AB  - BACKGROUND: African locust bean tree (Parkia biglobosa) is a multipurpose species
      used widely in arid Africa by local communities. The present study focused on
      ethnic differences in use values and use patterns of P. biglobosa in Northern
      Benin, where the species widely grows. The use values according to the various
      ethnic groups in the study area have been evaluated in detail for P. biglobosa.
      METHODS: From 13 ethnic groups, 1587 people were interviewed in the study area
      using semi-structured questionnaires. Principal Component Analysis was applied to
      analyze the use value and the use patterns of P. biglobosa for the different
      ethnic groups. RESULTS: All interviewees in the study area knew at least one use
      of P. biglobosa. The various uses identified were medicinal (47%), handicraft and
      domestic (3%), medico-magic (1%), veterinary (1%), cultural (1%), food (25%) and
      commercial (22%). The various parts involved in these types of uses were: fruits
      [shell (2%), pulp (22%) and seeds (36%)], bark (17%), leaves (9%), roots (3%),
      flowers (1%) and branches (10%). The ethnic group consensus values for P.
      biglobosa parts showed that the seeds are used the most. The interviewees
      diversity value (ID) and equitability value (IE) indicated that knowledge
      concerning P. biglobosa use was distributed homogeneously among the ethnic
      groups. CONCLUSIONS: P. biglobosa is well-known and used in different ways by the
      local populations in the study area. Local knowledge on the species is
      diversified and influenced by ethnic group. Ethnic differences in use values and
      use patterns of the species were evident in this study.

PMID- 22152044
TI  - ABO-incompatible lung transplantation in an infant.
AB  - Waitlist mortality continues to be a limiting factor for all solid-organ
      transplant programs. Strategies that could improve this situation should be
      considered. We report the first ABO-incompatible lung transplantation in an
      infant. The recipient infant was ABO blood group A1 and the donor group B. The
      recipient was diagnosed with surfactant protein B deficiency, which is a fatal
      condition and lung transplantation is the only definitive therapy. At 32 days of
      age, a bilateral lung transplantation from a donation after cardiac death (DCD)
      donor was performed. Intraoperative plasma exchange was the only preparatory
      procedure performed. No further interventions were required as the recipient
      isohemagglutinins were negative before transplant and have remained negative to
      date. At 6 months posttransplant, the recipient is at home, thriving, with normal
      development. This outcome suggests that ABO-incompatible lung transplantation is
      feasible in infants, providing another option to offer life-saving lung
      transplantation in this age range.

PMID- 22152046
TI  - Compound semiconductor nanotube materials grown and fabricated.
AB  - A new GaAs/InGaAs/InGaP compound semiconductor nanotube material structure was
      designed and fabricated in this work. A thin, InGaAs-strained material layer was
      designed in the nanotube structure, which can directionally roll up a strained
      heterostructure through a normal wet etching process. The compound semiconductor
      nanotube structure was grown by gas-source molecular beam epitaxy. A good
      crystalline quality of InGaP, InGaAs, and GaAs materials was obtained through
      optimizing the growth condition. The fabricated GaAs/InGaAs/InGaP semiconductor
      nanotubes, with a diameter of 300 to 350 nm and a length of 1.8 to 2.0 MUm, were
      achieved through normal device fabrication.

PMID- 22152045
TI  - Lactate in the critically ill patients: an outcome marker with the times.
AB  - Lactic acid was first discovered in human blood in 1843. Since then it has been
      used as a prognosticator of outcome in critical illness. Regardless of its
      etiology, lactate's presence and trend over time have been shown to be
      independently associated with mortality. Two dynamic lactate measures, the time
      weighted average lactate and the absolute change in lactate over the first 24
      hours in the ICU, were recently shown to be better than static lactate
      measurements in predicting hospital and ICU deaths.

PMID- 22152047
TI  - Evaluation of immunity against malaria using luciferase-expressing Plasmodium
      berghei parasites.
AB  - BACKGROUND: Measurement of liver stage development is of key interest in malaria
      biology and vaccine studies. Parasite development in liver cells can be
      visualized in real-time, both in culture and in live mice, using a transgenic
      Plasmodium berghei parasite, PbGFP-Luccon, expressing the bioluminescent reporter
      luciferase. This study explores the benefit of using these parasites for the
      evaluation of immunity against malaria, compared to qRT-PCR techniques in vivo
      and in vitro. METHODS: Mice were immunized with either radiation attenuated
      sporozoites (RAS) or wildtype sporozoites under chloroquine prophylaxis (CPS) and
      challenged with PbGFP-Luccon. The in vitro transgenic sporozoites neutralization
      assay (TSNA) was adapted by replacing PbCS(Pf) parasites for PbGFP-Luccon
      parasites. RESULTS: Application of PbGFP-Luccon transgenic parasites provides
      live quantitative visual information about the relation between parasite liver
      load and protection. Moreover, fast and reproducible results are obtained by
      using these parasites in the transgenic sporozoites neutralization assay,
      measuring functional antibody-mediated immune responses. CONCLUSIONS: PbGFP
      Luccon parasites are a straightforward and valuable tool for comprehension of the
      biological and immunological principles underlying protection against malaria.

PMID- 22152048
TI  - Test-retest reliability and construct validity of the ENERGY-child questionnaire
      on energy balance-related behaviours and their potential determinants: the ENERGY
      project.
AB  - BACKGROUND: Insight in children's energy balance-related behaviours (EBRBs) and
      their determinants is important to inform obesity prevention research. Therefore,
      reliable and valid tools to measure these variables in large-scale population
      research are needed. OBJECTIVE: To examine the test-retest reliability and
      construct validity of the child questionnaire used in the ENERGY-project,
      measuring EBRBs and their potential determinants among 10-12 year old children.
      METHODS: We collected data among 10-12 year old children (n = 730 in the test
      retest reliability study; n = 96 in the construct validity study) in six European
      countries, i.e. Belgium, Greece, Hungary, the Netherlands, Norway, and Spain.
      Test-retest reliability was assessed using the intra-class correlation
      coefficient (ICC) and percentage agreement comparing scores from two
      measurements, administered one week apart. To assess construct validity, the
      agreement between questionnaire responses and a subsequent face-to-face interview
      was assessed using ICC and percentage agreement. RESULTS: Of the 150
      questionnaire items, 115 (77%) showed good to excellent test-retest reliability
      as indicated by ICCs > .60 or percentage agreement >= 75%. Test-retest
      reliability was moderate for 34 items (23%) and poor for one item. Construct
      validity appeared to be good to excellent for 70 (47%) of the 150 items, as
      indicated by ICCs > .60 or percentage agreement >= 75%. From the other 80 items,
      construct validity was moderate for 39 (26%) and poor for 41 items (27%).
      CONCLUSIONS: Our results demonstrate that the ENERGY-child questionnaire,
      assessing EBRBs of the child as well as personal, family, and school
      environmental determinants related to these EBRBs, has good test-retest
      reliability and moderate to good construct validity for the large majority of
      items.

PMID- 22152049
TI  - Negotiating hope with chronic obstructive pulmonary disease patients: a
      qualitative study of patients and healthcare professionals.
AB  - BACKGROUND: The information needs of patients with chronic obstructive pulmonary
      disease (COPD) towards the end of life are poorly understood. AIM: This study
      explored the views of patients with COPD and healthcare professionals, focusing
      upon information needs and treatment preferences. METHOD: In-depth, semi
      structured interviews were held with patients with COPD following admission to
      hospital with respiratory failure, and focus groups held with healthcare
      professionals from hospital and community settings. RESULTS: Ten patients were
      interviewed, who had a median 4 previous hospital admissions, and had smoked for
      median 47 years. Five focus groups were held with 31 healthcare professionals (18
      nurses, 7 doctors, 6 allied health). The theme underpinning all discussions was
      of tension between maintaining hope and negotiating the reality of the illness
      and its consequences. Within this theme, patients tended to be optimistic, viewed
      acute exacerbations as separate from their underlying chronic illness, and were
      keen for intensive treatments, including intubation if acutely unwell. They had
      little understanding of the complexities of decision-making around treatment
      escalation. Both patients and health workers believed that information around end
      of life should be offered routinely, but delivered in a manner that recognises
      and maintains a form of hope. CONCLUSION: Patients and healthcare professionals
      believe information around illness course, future goals and treatment is
      important to care. An expanded view of hope may assist when providing such
      information, including when discussing goals of care in the setting of advanced
      illness.

PMID- 22152050
TI  - High level expression of Acidothermus cellulolyticus beta-1, 4-endoglucanase in
      transgenic rice enhances the hydrolysis of its straw by cultured cow gastric
      fluid.
AB  - BACKGROUND: Large-scale production of effective cellulose hydrolytic enzymes is
      the key to the bioconversion of agricultural residues to ethanol. The goal of
      this study was to develop a rice plant as a bioreactor for the large-scale
      production of cellulose hydrolytic enzymes via genetic transformation, and to
      simultaneously improve rice straw as an efficient biomass feedstock for
      conversion of cellulose to glucose. RESULTS: In this study, the cellulose
      hydrolytic enzyme beta-1, 4-endoglucanase (E1) gene, from the thermophilic
      bacterium Acidothermus cellulolyticus, was overexpressed in rice through
      Agrobacterium-mediated transformation. The expression of the bacterial E1 gene in
      rice was driven by the constitutive Mac promoter, a hybrid promoter of Ti plasmid
      mannopine synthetase promoter and cauliflower mosaic virus 35S promoter enhancer,
      with the signal peptide of tobacco pathogenesis-related protein for targeting the
      E1 protein to the apoplastic compartment for storage. A total of 52 transgenic
      rice plants from six independent lines expressing the bacterial E1 enzyme were
      obtained that expressed the gene at high levels without severely impairing plant
      growth and development. However, some transgenic plants exhibited a shorter
      stature and flowered earlier than the wild type plants. The E1 specific
      activities in the leaves of the highest expressing transgenic rice lines were
      about 20-fold higher than those of various transgenic plants obtained in previous
      studies and the protein amounts accounted for up to 6.1% of the total leaf
      soluble protein. A zymogram and temperature-dependent activity analyses
      demonstrated the thermostability of the E1 enzyme and its substrate specificity
      against cellulose, and a simple heat treatment can be used to purify the protein.
      In addition, hydrolysis of transgenic rice straw with cultured cow gastric fluid
      for one hour at 39 degrees C and another hour at 81 degrees C yielded 43% more
      reducing sugars than wild type rice straw. CONCLUSION: Taken together, these data
      suggest that transgenic rice can effectively serve as a bioreactor for the large
      scale production of active, thermostable cellulose hydrolytic enzymes. As a
      feedstock, direct expression of large amount of cellulases in transgenic rice may
      also facilitate saccharification of cellulose in rice straw and significantly
      reduce the costs for hydrolytic enzymes.

PMID- 22152051
TI  - A highly efficient green synthesis of 1, 8-dioxo-octahydroxanthenes.
AB  - SmCl3 (20 mol%) has been used as an efficient catalyst for reaction between
      aromatic aldehydes and 5,5-dimethyl-1,3-cyclohexanedione at 120 degrees C to give
      1,8-dioxo-octahydroxanthene derivatives in high yield. The same reaction in
      water, at room temperature gave only the open chain analogue of 1,8-dioxo
      octahydroxanthene. Use of eco-friendly green Lewis acid, readily available
      catalyst and easy isolation of the product makes this a convenient method for the
      synthesis of either of the products.

PMID- 22152052
TI  - Food choices and practices during pregnancy of immigrant and Aboriginal women in
      Canada: a study protocol.
AB  - BACKGROUND: Facilitating the provision of appropriate health care for immigrant
      and Aboriginal populations in Canada is critical for maximizing health potential
      and well-being. Numerous reports describe heightened risks of poor maternal and
      birth outcomes for immigrant and Aboriginal women. Many of these outcomes may
      relate to food consumption/practices and thus may be obviated through provision
      of resources which suit the women's ethnocultural preferences. This project aims
      to understand ethnocultural food and health practices of Aboriginal and immigrant
      women, and how these intersect with respect to the legacy of Aboriginal
      colonialism and to the social contexts of cultural adaptation and adjustment of
      immigrants. The findings will inform the development of visual tools for health
      promotion by practitioners. METHODS/DESIGN: This four-phase study employs a case
      study design allowing for multiple means of data collection and different units
      of analysis. Phase 1 consists of a scoping review of the literature. Phases 2 and
      3 incorporate pictorial representations of food choices (photovoice in Phase 2)
      with semi-structured photo-elicited interviews (in Phase 3). The findings from
      Phases 1-3 and consultations with key stakeholders will generate key
      understandings for Phase 4, the production of culturally appropriate visual
      tools. For the scoping review, an emerging methodological framework will be
      utilized in addition to systematic review guidelines. A research librarian will
      assist with the search strategy and retrieval of literature. For Phases 2 and 3,
      recruitment of 20-24 women will be facilitated by team member affiliations at
      perinatal clinics in one of the city's most diverse neighbourhoods. The
      interviews will reveal culturally normative practices surrounding maternal food
      choices and consumption, including how women negotiate these practices within
      their own worldview and experiences. A structured and comprehensive integrated
      knowledge translation plan has been formulated. DISCUSSION: The findings of this
      study will provide practitioners with an understanding of the cultural
      differences that affect women's dietary choices during maternity. We expect that
      the developed resources will be of immediate use within the women's units and
      will enhance counseling efforts. Wide dissemination of outputs may have a greater
      long term impact in the primary and secondary prevention of these high risk
      conditions.

PMID- 22152053
TI  - Genome dedoubling by DCJ and reversal.
AB  - BACKGROUND: Segmental duplications in genomes have been studied for many years.
      Recently, several studies have highlighted a biological phenomenon called
      breakpoint-duplication that apparently associates a significant proportion of
      segmental duplications in Mammals, and the Drosophila species group, to
      breakpoints in rearrangement events. RESULTS: In this paper, we introduce and
      study a combinatorial problem, inspired from the breakpoint-duplication
      phenomenon, called the Genome Dedoubling Problem. It consists of finding a
      minimum length rearrangement scenario required to transform a genome with
      duplicated segments into a non-duplicated genome such that duplications are
      caused by rearrangement breakpoints. We show that the problem, in the Double-Cut
      and-Join (DCJ) and the reversal rearrangement models, can be reduced to an APX
      complete problem, and we provide algorithms for the Genome Dedoubling Problem
      with 2-approximable parts. We apply the methods for the reconstruction of a non
      duplicated ancestor of Drosophila yakuba. CONCLUSIONS: We present the Genome
      Dedoubling Problem, and describe two algorithms solving the problem in the DCJ
      model, and the reversal model. The usefulness of the problems and the methods are
      showed through an application to real Drosophila data.

PMID- 22152054
TI  - The effects of a cafeteria diet on insulin production and clearance in rats.
AB  - The aim of the present study was to determine the effects of a cafeteria diet on
      the function and apoptosis of the pancreas, and the activity and expression of
      the insulin-degrading enzyme (IDE). Female Wistar rats were fed either with a
      cafeteria diet or a control diet for 17 weeks, and blood and tissues were then
      collected for analysis. The cafeteria diet-treated rats had higher plasma insulin
      and C-peptide levels (P<0.05), showing increased insulin secretion by the
      pancreas. Insulin protein and gene expression levels were higher in the pancreas
      of obese rats, as was its transcriptional controller, pancreatic duodenal
      homeobox 1 (P<0.05). Feeding a cafeteria diet down-regulated the gene expression
      of the anti-apoptotic marker B-cell/lymphoma 2 (BCL2), and up-regulated the
      protein levels of BCL2-associated X protein, a pro-apoptotic marker (P<0.05). The
      cafeteria diet caused lipid accumulation in the pancreas and modified the
      expression of key genes that control lipid metabolism. To assay whether insulin
      clearance was also modified, we checked the activity of the IDE, one of the
      enzymes responsible for insulin clearance. We found increased liver IDE activity
      (P<0.05) in the cafeteria diet-fed animals, which could, in part, be due to an up
      regulation of its gene expression. Conversely, IDE gene expression was unmodified
      in the kidney and adipose tissue; although when the adipose tissue weight was
      considered, the insulin clearance potential was higher in the cafeteria diet
      treated rats. In conclusion, treatment with a cafeteria diet for 17 weeks in rats
      mimicked a pre-diabetic state, with ectopic lipid accumulation in the pancreas,
      and increased the IDE-mediated insulin clearance capability.

PMID- 22152056
TI  - Ecological niche modelling of the Bacillus anthracis A1.a sub-lineage in
      Kazakhstan.
AB  - BACKGROUND: Bacillus anthracis, the causative agent of anthrax, is a globally
      distributed zoonotic pathogen that continues to be a veterinary and human health
      problem in Central Asia. We used a database of anthrax outbreak locations in
      Kazakhstan and a subset of genotyped isolates to model the geographic
      distribution and ecological associations of B. anthracis in Kazakhstan. The aims
      of the study were to test the influence of soil variables on a previous
      ecological niche based prediction of B. anthracis in Kazakhstan and to determine
      if a single sub-lineage of B. anthracis occupies a unique ecological niche.
      RESULTS: The addition of soil variables to the previously developed ecological
      niche model did not appreciably alter the limits of the predicted geographic or
      ecological distribution of B. anthracis in Kazakhstan. The A1.a experiment
      predicted the sub-lineage to be present over a larger geographic area than did
      the outbreak based experiment containing multiple lineages. Within the geographic
      area predicted to be suitable for B. anthracis by all ten best subset models, the
      A1.a sub-lineage was associated with a wider range of ecological tolerances than
      the outbreak-soil experiment. Analysis of rule types showed that logit rules
      predominate in the outbreak-soil experiment and range rules in the A1.a sub
      lineage experiment. Random sub-setting of locality points suggests that models of
      B. anthracis distribution may be sensitive to sample size. CONCLUSIONS: Our
      analysis supports careful consideration of the taxonomic resolution of data used
      to create ecological niche models. Further investigations into the environmental
      affinities of individual lineages and sub-lineages of B. anthracis will be useful
      in understanding the ecology of the disease at large and small scales. With model
      based predictions serving as approximations of disease risk, these efforts will
      improve the efficacy of public health interventions for anthrax prevention and
      control.

PMID- 22152055
TI  - Review article: Use of ultrasound in the developing world.
AB  - As portability and durability improve, bedside, clinician-performed ultrasound
      is seeing increasing use in rural, underdeveloped parts of the world. Physicians,
      nurses and medical officers have demonstrated the ability to perform and
      interpret a large variety of ultrasound exams, and a growing body of literature
      supports the use of point-of-care ultrasound in developing nations. We review, by
      region, the existing literature in support of ultrasound use in the developing
      world and training guidelines currently in use, and highlight indications for
      emergency ultrasound in the developing world. We suggest future directions for
      bedside ultrasound use and research to improve diagnostic capacity and patient
      care in the most remote areas of the globe.

PMID- 22152058
TI  - Cloning and sequencing of Indian water buffalo (Bubalus bubalis) interleukin-3
      cDNA.
AB  - Full-length cDNA (435 bp) of the interleukin-3(IL-3) gene of the Indian water
      buffalo was amplified by reverse transcriptase-polymerase chain reaction and
      sequenced. This sequence had 96% nucleotide identity and 92% amino acid identity
      with bovine IL-3. There are 10 amino acid substitutions in buffalo compared with
      that of bovine. The amino acid sequence of buffalo IL-3 also showed very high
      identity with that of other ruminants, indicating functional cross-reactivity.
      Structural homology modelling of buffalo IL-3 protein with human IL-3 showed the
      presence of five helical structures.

PMID- 22152057
TI  - CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle
      strength.
AB  - Declining muscle strength is a core feature of aging. Several mechanisms have
      been postulated, including CCAAT/enhancer-binding protein-beta (C/EBP-beta)
      triggered macrophage-mediated muscle fiber regeneration after micro-injury,
      evidenced in a mouse model. We aimed to identify in vivo circulating leukocyte
      gene expression changes associated with muscle strength in the human adult
      population. We undertook a genome-wide expression microarray screen, using
      peripheral blood RNA samples from InCHIANTI study participants (aged 30 and 104).
      Logged expression intensities were regressed with muscle strength using models
      adjusted for multiple confounders. Key results were validated by real-time PCR.
      The Short Physical Performance Battery (SPPB) score tested walk speed, chair
      stand, and balance. CEBPB expression levels were associated with muscle strength
      (beta coefficient = 0.20560, P = 1.03*10(-6), false discovery rate q = 0.014).
      The estimated handgrip strength in 70-year-old men in the lowest CEBPB expression
      tertile was 35.2 kg compared with 41.2 kg in the top tertile. CEBPB expression
      was also associated with hip, knee, ankle, and shoulder strength and the SPPB
      score (P = 0.018). Near-study-wide associations were also noted for TGF-beta3 (P
      = 3.4*10(-5) , q = 0.12) and CEBPD expression (P = 9.7*10(-5) , q = 0.18) but not
      for CEBPA expression. We report here a novel finding that raised CEBPB expression
      in circulating leukocyte-derived RNA samples in vivo is associated with greater
      muscle strength and better physical performance in humans. This association may
      be consistent with mouse model evidence of CEBPB-triggered muscle repair: if this
      mechanism is confirmed, it may provide a target for intervention to protect and
      enhance aging muscle.

PMID- 22152059
TI  - Decrease in the production of beta-amyloid by berberine inhibition of the
      expression of beta-secretase in HEK293 cells.
AB  - BACKGROUND: Berberine (BER), the major alkaloidal component of Rhizoma coptidis,
      has multiple pharmacological effects including inhibition of
      acetylcholinesterase, reduction of cholesterol and glucose levels, anti
      inflammatory, neuroprotective and neurotrophic effects. It has also been
      demonstrated that BER can reduce the production of beta-amyloid40/42, which plays
      a critical and primary role in the pathogenesis of Alzheimer's disease. However,
      the mechanism by which it accomplishes this remains unclear. RESULTS: Here, we
      report that BER could not only significantly decrease the production of beta
      amyloid40/42 and the expression of beta-secretase (BACE), but was also able to
      activate the extracellular signal-regulated kinase1/2 (ERK1/2) pathway in a dose-
      and time-dependent manner in HEK293 cells stably transfected with APP695
      containing the Swedish mutation. We also find that U0126, an antagonist of the
      ERK1/2 pathway, could abolish (1) the activation activity of BER on the ERK1/2
      pathway and (2) the inhibition activity of BER on the production of beta
      amyloid40/42 and the expression of BACE. CONCLUSION: Our data indicate that BER
      decreases the production of beta-amyloid40/42 by inhibiting the expression of
      BACE via activation of the ERK1/2 pathway.

PMID- 22152061
TI  - Assessment scores in H1N1 infection.

PMID- 22152060
TI  - Selection of recombinant MVA by rescue of the essential D4R gene.
AB  - Modified vaccinia virus Ankara (MVA) has become a promising vaccine vector due to
      its immunogenicity and its proven safety in humans. As a general approach for
      stringent and rapid selection of recombinant MVA, we assessed marker rescue of
      the essential viral D4R gene in an engineered deletion mutant that is fully
      replication defective in wild-type cells. Recombinant, replicating virus was
      obtained by re-introduction of the deleted viral gene as a dominant selection
      marker into the deletion mutant.

PMID- 22152062
TI  - Efficiency, error and yield in light-directed maskless synthesis of DNA
      microarrays.
AB  - BACKGROUND: Light-directed in situ synthesis of DNA microarrays using computer
      controlled projection from a digital micromirror device--maskless array synthesis
      (MAS)--has proved to be successful at both commercial and laboratory scales. The
      chemical synthetic cycle in MAS is quite similar to that of conventional solid
      phase synthesis of oligonucleotides, but the complexity of microarrays and unique
      synthesis kinetics on the glass substrate require a careful tuning of parameters
      and unique modifications to the synthesis cycle to obtain optimal deprotection
      and phosphoramidite coupling. In addition, unintended deprotection due to
      scattering and diffraction introduce insertion errors that contribute
      significantly to the overall error rate. RESULTS: Stepwise phosphoramidite
      coupling yields have been greatly improved and are now comparable to those
      obtained in solid phase synthesis of oligonucleotides. Extended chemical exposure
      in the synthesis of complex, long oligonucleotide arrays result in lower--but
      still high--final average yields which approach 99%. The new synthesis chemistry
      includes elimination of the standard oxidation until the final step, and improved
      coupling and light deprotection. Coupling Insertions due to stray light are the
      limiting factor in sequence quality for oligonucleotide synthesis for gene
      assembly. Diffraction and local flare are by far the largest contributors to loss
      of optical contrast. CONCLUSIONS: Maskless array synthesis is an efficient and
      versatile method for synthesizing high density arrays of long oligonucleotides
      for hybridization- and other molecular binding-based experiments. For
      applications requiring high sequence purity, such as gene assembly, diffraction
      and flare remain significant obstacles, but can be significantly reduced with
      straightforward experimental strategies.

PMID- 22152063
TI  - High Resolution Melt (HRM) analysis is an efficient tool to genotype EMS mutants
      in complex crop genomes.
AB  - BACKGROUND: Targeted Induced Loci Lesions IN Genomes (TILLING) is increasingly
      being used to generate and identify mutations in target genes of crop genomes.
      TILLING populations of several thousand lines have been generated in a number of
      crop species including Brassica rapa. Genetic analysis of mutants identified by
      TILLING requires an efficient, high-throughput and cost effective genotyping
      method to track the mutations through numerous generations. High resolution melt
      (HRM) analysis has been used in a number of systems to identify single nucleotide
      polymorphisms (SNPs) and insertion/deletions (IN/DELs) enabling the genotyping of
      different types of samples. HRM is ideally suited to high-throughput genotyping
      of multiple TILLING mutants in complex crop genomes. To date it has been used to
      identify mutants and genotype single mutations. The aim of this study was to
      determine if HRM can facilitate downstream analysis of multiple mutant lines
      identified by TILLING in order to characterise allelic series of EMS induced
      mutations in target genes across a number of generations in complex crop genomes.
      RESULTS: We demonstrate that HRM can be used to genotype allelic series of
      mutations in two genes, BraA.CAX1a and BraA.MET1.a in Brassica rapa. We analysed
      12 mutations in BraA.CAX1.a and five in BraA.MET1.a over two generations
      including a back-cross to the wild-type. Using a commercially available HRM kit
      and the LightscannerTM system we were able to detect mutations in heterozygous
      and homozygous states for both genes. CONCLUSIONS: Using HRM genotyping on
      TILLING derived mutants, it is possible to generate an allelic series of
      mutations within multiple target genes rapidly. Lines suitable for phenotypic
      analysis can be isolated approximately 8-9 months (3 generations) from receiving
      M3 seed of Brassica rapa from the RevGenUK TILLING service.

PMID- 22152064
TI  - Advances in direct T-cell alloreactivity: function, avidity, biophysics and
      structure.
AB  - Although T-cell-based adaptive immunity plays a crucial role in protection
      against infectious pathogens and uncontrolled outgrowth of malignant cells, a
      large portion of these T cells are also capable of responding to allogeneic HLA
      molecules, violating the paradigm of self-major histocompatibility complex (MHC)
      restriction. Recent studies have provided insights into the mechanisms by which
      these T cells recognize allogeneic targets. The role of antiviral T cells in
      direct alloreactivity through peptide-dependent molecular mimicry and alternate
      peptide-MHC docking modes has emerged as major models for the human alloresponse.
      Here, we review in depth recent advances in this field and discuss how molecular
      interactions between T cells and HLA molecules drive the activation of these
      effector cells and its potential implications for alloreactivity in human
      transplantation.

PMID- 22152066
TI  - Influence of helium-ion bombardment on the optical properties of ZnO nanorods/p
      GaN light-emitting diodes.
AB  - Light-emitting diodes (LEDs) based on zinc oxide (ZnO) nanorods grown by vapor
      liquid-solid catalytic growth method were irradiated with 2-MeV helium (He+)
      ions. The fabricated LEDs were irradiated with fluencies of approximately 2 *
      1013 ions/cm2 and approximately 4 * 1013 ions/cm2. Scanning electron microscopy
      images showed that the morphology of the irradiated samples is not changed. The
      as-grown and He+-irradiated LEDs showed rectifying behavior with the same I-V
      characteristics. Photoluminescence (PL) measurements showed that there is a blue
      shift of approximately 0.0347 and 0.082 eV in the near-band emission (free
      exciton) and green emission of the irradiated ZnO nanorods, respectively. It was
      also observed that the PL intensity of the near-band emission was decreased after
      irradiation of the samples. The electroluminescence (EL) measurements of the
      fabricated LEDs showed that there is a blue shift of 0.125 eV in the broad green
      emission after irradiation and the EL intensity of violet emission approximately
      centered at 398 nm nearly disappeared after irradiations. The color-rendering
      properties show a small decrease in the color-rendering indices of 3% after 2 MeV
      He+ ions irradiation.

PMID- 22152065
TI  - Primaquine in vivax malaria: an update and review on management issues.
AB  - Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952.
      It has remained the only FDA licensed drug capable of clearing the intra-hepatic
      schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on
      five major aspects of primaquine use in treatment of vivax malaria, namely: a)
      evidence of efficacy of primaquine for its current indications; b) potential
      hazards of its widespread use, c) critical analysis of reported resistance
      against primaquine containing regimens; d) evidence for combining primaquine with
      artemisinins in areas of chloroquine resistance; and e) the potential for
      replacement of primaquine with newer drugs.

PMID- 22152068
TI  - Opposite temperature effect on transport activity of KCC2/KCC4 and N(K)CCs in HEK
      293 cells.
AB  - BACKGROUND: Cation chloride cotransporters play essential roles in many
      physiological processes such as volume regulation, transepithelial salt transport
      and setting the intracellular chloride concentration in neurons. They consist
      mainly of the inward transporters NCC, NKCC1, and NKCC2, and the outward
      transporters KCC1 to KCC4. To gain insight into regulatory and structure-function
      relationships, precise determination of their activity is required. Frequently,
      these analyses are performed in HEK-293 cells. Recently the activity of the
      inward transporters NKCC1 and NCC was shown to increase with temperature in these
      cells. However, the temperature effect on KCCs remains largely unknown. FINDINGS:
      Here, we determined the temperature effect on KCC2 and KCC4 transport activity in
      HEK-293 cells. Both transporters demonstrated significantly higher transport
      activity (2.5 fold for KCC2 and 3.3 fold for KCC4) after pre-incubation at room
      temperature compared to 37 degrees C. CONCLUSIONS: These data identify a
      reciprocal temperature dependence of cation chloride inward and outward
      cotransporters in HEK-293 cells. Thus, lower temperature should be used for
      functional characterization of KCC2 and KCC4 and higher temperatures for N(K)CCs
      in heterologous mammalian expression systems. Furthermore, if this reciprocal
      effect also applies to neurons, the action of inhibitory neurotransmitters might
      be more affected by changes in temperature than previously thought.

PMID- 22152067
TI  - Definition of the viral targets of protective HIV-1-specific T cell responses.
AB  - BACKGROUND: The efficacy of the CTL component of a future HIV-1 vaccine will
      depend on the induction of responses with the most potent antiviral activity and
      broad HLA class I restriction. However, current HIV vaccine designs are largely
      based on viral sequence alignments only, not incorporating experimental data on T
      cell function and specificity. METHODS: Here, 950 untreated HIV-1 clade B or -C
      infected individuals were tested for responses to sets of 410 overlapping
      peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective
      ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP
      non-responders and responders. RESULTS: For both clades, there was a negative
      relationship between the PR and the entropy of the OLP sequence. There was also a
      significant additive effect of multiple responses to beneficial OLP. Responses to
      beneficial OLP were of significantly higher functional avidity than responses to
      non-beneficial OLP. They also had superior in-vitro antiviral activities and,
      importantly, were at least as predictive of individuals' viral loads than their
      HLA class I genotypes. CONCLUSIONS: The data thus identify immunogen sequence
      candidates for HIV and provide an approach for T cell immunogen design applicable
      to other viral infections.

PMID- 22152069
TI  - Impaired neural response to internal but not external feedback in schizophrenia.
AB  - BACKGROUND: Accurate monitoring and integration of both internal and external
      feedback is crucial for guiding current and future behavior. These aspects of
      performance monitoring are commonly indexed by two event-related potential (ERP)
      components: error-related negativity (ERN) and feedback negativity (FN). The ERN
      indexes internal response monitoring and is sensitive to the commission of
      erroneous versus correct responses, and the FN indexes external feedback
      monitoring of positive versus negative outcomes. Although individuals with
      schizophrenia consistently demonstrate a diminished ERN, the integrity of the FN
      has received minimal consideration. METHOD: The current research sought to
      clarify the scope of feedback processing impairments in schizophrenia in two
      studies: study 1 examined the ERN elicited in a flanker task in 16 out-patients
      and 14 healthy controls; study 2 examined the FN on a simple monetary gambling
      task in expanded samples of 35 out-patients and 33 healthy controls. RESULTS:
      Study 1 replicated prior reports of an impaired ERN in schizophrenia. By
      contrast, patients and controls demonstrated comparable FN differentiation
      between reward and non-reward feedback in study 2. CONCLUSIONS: The differential
      pattern across tasks suggests that basic sensitivity to external feedback
      indicating reward versus non-reward is intact in schizophrenia, at least under
      the relatively simple task conditions used in this study. Further efforts to
      specify intact and impaired reward-processing subcomponents in schizophrenia may
      help to shed light on the diminished motivation and goal-seeking behavior that
      are commonly seen in this disorder.

PMID- 22152070
TI  - Identification of alpha(1,6)fucosylated proteins differentially expressed in
      human colorectal cancer.
AB  - BACKGROUND: A universal hallmark of cancer cells is the change in their
      glycosylation phenotype. One of the most frequent alterations in the normal
      glycosylation pattern observed during carcinogenesis is the enhancement of
      alpha(1,6)linked fucose residues of glycoproteins, due to the up-regulation of
      the alpha(1,6)fucosyltransferase activity. Our previous results demonstrated the
      specific alteration of this enzyme activity and expression in colorectal cancer,
      suggesting its implication in tumour development and progression. METHODS: In the
      current work we combined a LCA-affinity chromatography with SDS-PAGE and mass
      spectrometry in order to identify alpha(1,6)fucosylated proteins differentially
      expressed in colorectal cancer. This strategy allowed the identification of a
      group of alpha(1,6)fucosylated proteins candidates to be involved in CRC
      malignancy. RESULTS: The majority of the identified proteins take part in cell
      signaling and interaction processes as well as in modulation of the immunological
      response. Likewise, we confirmed the increased expression of GRP94 in colorectal
      cancer tissue and the significant down-regulation of the IgGFcBP expression in
      tumour cells. CONCLUSION: All these results validate the importance of core
      fucosylated proteins profile analysis to understand the mechanisms which promote
      cancer onset and progression and to discover new tumour markers or therapeutic
      targets.

PMID- 22152071
TI  - Visual diagnosis: Rectal foreign body: A primer for emergency physicians.
AB  - We present a case that is occasionally seen within emergency departments, namely
      a rectal foreign body. After presentation of the case, a discussion concerning
      this entity is given, with practical information on necessity of an accurate and
      thorough history and removal of the object for clinicians.

PMID- 22152072
TI  - Is there an underestimation of intima-media thickness based on M-mode ultrasound
      technique in the abdominal aorta?
AB  - Measuring intima-media thickness (IMT) in the common carotid artery (CCA) is a
      valuable resource for the evaluation of subclinical atherosclerosis. The main
      objective of this study was to explore whether a B-mode ultrasound technique,
      Philips ATL, and an M-mode ultrasound technique, Wall Track System (WTS), show
      interchangeable results when measured in CCA and the abdominal aorta (AA). A
      total of 24 healthy, young subjects were examined. IMT and lumen diameter (LD) of
      the AA and the CCA were measured twice by two skilled ultrasonographers with two
      different ultrasound equipment B-mode: (Philips, ATL and M-mode: WTS).The intra
      observer variability of IMT in CCA and AA using B-mode showed a coefficient of
      variation 8% and 9%, and with M-mode 11% and 15%, respectively. Interobserver
      variability of IMT in CCA and AA using B-mode was 6% and 12%, and with M-mode 11%
      and 18%, respectively. CCA IMT was 0.53 +/- 0.07 and 0.53 +/- 0.09 mm using B
      mode and M-mode, respectively. However, in AA, IMT was 0.61 +/- 0.05 and 0.54 +/-
      0.10 mm using B-mode and M-mode, respectively. Thus, AA IMT was 11.5% thicker
      using B-mode (P < 0.01). We received adequate IMT readings from the carotid
      artery as well as the AA using two commonly used B-mode and M-mode techniques. B
      mode technique seems to show less variability, especially in the AA. More
      importantly, the two techniques measured different IMT thickness in the aorta,
      emphasizing the importance of using similar technique when comparing the impact
      of absolute values of IMT on cardiovascular disease.

PMID- 22152073
TI  - Calculation of right ventricular stroke volume in short-axis MR images using the
      equation of the tricuspid plane.
AB  - Short-axis (SA) magnetic resonance (MR) images are commonly planned parallel to
      the left atrioventricular valve. This orientation leads to oblique slices of the
      right ventricle (RV) with subsequent difficulties in separating the RV from the
      right atrium in the SA images. The insertion points of the tricuspid valve (TV)
      in the myocardium can be clearly identified in the right ventricle long axis
      (RVLA) and four-chamber (4CH) views. The purpose of this study was to develop a
      method that transfers the position of the tricuspid plane, as seen in the RVLA
      and 4CH views, to the SA images to facilitate the separation of the RV from the
      atrium. This methodology, termed Dissociating the Right Atrium from the Ventricle
      Volume (DRAW), was applied in 20 patients for calculations of right ventricular
      stroke volume (RVSV). The RVSV using DRAW (RVSV(DRAW)) was compared to left
      ventricular stroke volumes (LVSV) obtained from flow measurements in the
      ascending aorta. The RVSV was also determined using the conventional method
      (RVSV(CONV)) where the stack of images from the SA views are summarized, and a
      visual decision is made of the most basal slice to be included in the RV. The
      mean difference between RVSV(DRAW) and LVSV was 0.1 +/- 12.7 ml, while the mean
      difference between RVSV(CONV) and LVSV was 0.33 +/- 14.3 ml. Both the intra- and
      interobserver variability were small using the DRAW methodology, 0.6 +/- 3.5 and
      1.7 +/- 2.7 ml, respectively. In conclusion, the DRAW method can be used to
      facilitate the separation of the RV and the atrium.

PMID- 22152074
TI  - Response patterns to bronchodilator and quantitative computed tomography in
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) show
      different spirometric response patterns to bronchodilator, such that some
      patients show improvement principally in expiratory flow (forced expiratory
      volume in 1 s; FEV(1)), whereas others respond by improvement of lung volume
      (forced vital capacity; FVC). The mechanisms of these different response patterns
      to bronchodilator remain unclear. We investigated the associations between
      bronchodilator responsiveness and quantitative computed tomography (CT) indices
      in patients with COPD. METHODS: Data on a total of 101 patients with stable COPD
      were retrospectively analysed. Volume and flow responses to bronchodilator were
      assessed by FVC and FEV(1) changes before and after inhalation of salbutamol (400
      MUg). Volumetric CT was performed to quantify emphysema, air trapping and large
      airway thickness. Emphysema was assessed by the volume fraction of the lung under
      -950 Hounsfield units (HU; V(950)) at full inspiration and air trapping by the
      ratio of mean lung density (MLD) at full expiration and inspiration. Airway wall
      thickness and wall area percentage (WA%; defined as wall area/[wall area + lumen
      area] * 100), were measured near the origin of right apical and left apico
      posterior bronchus. RESULTS: Among quantitative CT indices, the CT emphysema
      index (V(950 insp)) showed a significant negative correlation with
      postbronchodilator FEV(1) change (R = -0.213, P = 0.004), and the CT air-trapping
      index correlated positively with postbronchodilator FVC change(R = 0.286,
      P<=0.001). Multiple linear regression analysis showed that CT emphysema index had
      independent association with postbronchodilator FEV(1) change and CT air-trapping
      index with postbronchodilator FVC change. CONCLUSION: The degrees of emphysema
      and air trapping may contribute to the different response patterns to
      bronchodilator in patients with COPD.

PMID- 22152075
TI  - Technetium-99m-labelled HL91 and technetium-99m-labelled MIBI SPECT imaging for
      the detection of ischaemic viable myocardium: a preliminary study.
AB  - PURPOSE: The assessment of myocardial viability has become an important aspect of
      the diagnostic and prognostic work-up of patients with coronary artery disease.
      Technetium-99m labelled sestamibi ((99m)Tc-MIBI) myocardial perfusion imaging may
      underestimate the viability of ischaemic myocardium. Technetium-99m labelled 4,9
      diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime ((99m)Tc-HL91) is a hypoxia
      avid agent which can identify acutely ischaemic viable myocardium in a canine
      model using a standard gamma camera. The aim of this study was to evaluate uptake
      character of ischaemic viable myocardium and diagnostic performance of single
      photon emission computed tomography (SPECT) imaging by (99m)Tc-HL91 and (99m)Tc
      MIBI in detecting ischaemic viable myocardium in coronary heart disease. METHODS:
      A total of 41 patients with coronary artery disease were recruited from March
      2008 to May 2009. For detecting ischaemic viable myocardium, SPECT imaging by
      (99m)Tc-HL91 and (99m)Tc-MIBI were performed in all patients before coronary
      revascularization. Six patients with single ischaemic myocardial segment received
      a 2-day SEPCT/CT imaging protocol and the uptake of (99m)Tc-HL91 in ischaemic
      myocardium was quantitatively analysed. The remaining 35 patients received a 1
      day (99m)Tc-HL91 and (99m)Tc-MIBI SPECT imaging protocol. Resting (99m)Tc-MIBI
      myocardial perfusion imaging in 3-18 months after revascularization was used as
      the standard methodology to evaluate the myocardial viability. RESULTS: In 41
      patients, 66 ischaemic myocardial segments were proven to be viable and 12 to be
      necrotic by resting (99m)Tc-MIBI myocardial perfusion imaging after coronary
      revascularization. Furthermore, 60 viable segments with negative uptake of
      (99m)Tc-MIBI showed positive uptake of (99m)Tc-HL91. The remaining six viable
      segments and 12 necrotic segments showed both negative uptake of (99m)Tc-HL91 and
      (99m)Tc-MIBI. The sensitivity, specificity, accuracy, Younden Index, positive
      predictive value and negative predictive value for evaluating ischaemic viable
      myocardium were 90.9%, 100%, 92.3%, 90.9%, 100% and 66.7%, respectively.
      Ischaemic viable myocardium had the negative (99m)Tc-MIBI uptake and positive
      (99m)Tc-HL91 uptake, which demonstrated a mismatched uptake character.
      Quantitative analysis indicated the uptake of (99m)Tc-HL91 in viable myocardium
      was increasing in the first 1-3 h and remained stable at the 3-4 h after
      injection. CONCLUSION: Functional SPECT imaging with (99m)Tc-HL91 and (99m)Tc
      MIBI can be used to detect the seriously ischaemic but viable myocardium with a
      mismatched uptake character. The uptake of (99m)Tc-HL91 in the viable myocardium
      reached a stable level at 3-4 h after injection.

PMID- 22152076
TI  - Quantification of myocardium at risk in myocardial perfusion SPECT by co
      registration and fusion with delayed contrast-enhanced magnetic resonance imaging
      -an experimental ex vivo study.
AB  - BACKGROUND: Myocardial perfusion single-photon emission computed tomography (MPS)
      can be used to assess myocardium at risk in occlusive coronary ischaemia. The aim
      was to develop a method to quantify myocardium at risk as perfusion defect size
      on ex vivo MPS using co-registration and fusion with ex vivo magnetic resonance
      imaging (MRI). METHODS: Pigs (n = 19) were injected 99mTc-tetrofosmin prior to
      concluding 40 min of coronary artery occlusion, followed by reperfusion and MRI
      contrast injection. The excised heart was imaged with T1-weighted MRI and MPS,
      and images were co-registered using freely available software (Segment v1.8,
      http://segment.heiberg.se). The left ventricle was semi-automatically delineated
      in MRI and copied to MPS. The threshold for a MPS perfusion defect was defined as
      the mean counts in the MPS image at the MRI-determined border between remote
      myocardium and air. The threshold was measured using count maxima set to the
      100th-95th percentile of counts within the myocardium. The count maximum that
      gave the lowest threshold variability (SD) was considered the most robust.
      RESULTS: A count maximum using the 100th percentile yielded a threshold of (mean
      +/- SD) 55 +/- 6.2%. This method showed the lowest SD compared to 99th-95th
      percentile count maxima (6.6-7.2%). CONCLUSIONS: We describe a method for
      objective quantification of myocardium at risk as perfusion defect size on MPS
      using knowledge of the anatomy of the myocardium from co-registered MRI. This
      enables simultaneous quantification of myocardium at risk by MPS and infarct size
      by MRI for the evaluation of treatments for myocardial infarction.

PMID- 22152077
TI  - The incidence of plateau at VO(2max) is affected by a bout of prior-priming
      exercise.
AB  - The purpose of this study was to determine the effect of 6 min of prior-priming
      exercise on the incidence of plateau at VO(2max). Twelve trained cyclists (age,
      21 +/- 3 years; height, 175.0 +/- 8.0 cm; weight, 69.0 +/- 10.4 kg; maximal
      oxygen uptake (VO(2max)), 56.3 +/- 6.9 ml kg(-1) min(-1)) completed three
      incremental tests to volitional exhaustion, which were classified as unprimed
      (UP), heavy-primed (HP) and severe-primed (SP), at a work rate of 1 W 2 s(-1),
      from an initial workload of 100 W, for the determination of VO(2max). VO(2max)
      trial in the HP and SP conditions was preceded by a period of 4-min unloaded
      cycling followed by a further 6 min of constant load cycling at Delta50% VO(2)
      gas exchange threshold (GET)-VO(2max) (HP) and Delta75% VO(2) GET-VO(2max) (SP).
      Expired air was recorded on a breath-by-breath basis during all trials. The
      criteria adopted for a plateau in VO(2max) was a DeltaVO(2) over the final two
      consecutive 30-s sampling periods <= 2.1 ml kg(-1) min(-1). There was a
      significant increase in plateau responses between the UP (50%) and HP (100%)
      conditions (P = 0.001) coupled with a significant change in the slope of the
      regression line during the final 60 s of the VO(2max) test, UP and HP (P =
      0.0299) and UP and SP (P = 0.0296). These data suggest that a bout of prior
      priming exercise promotes an increased incidence of plateau responses at VO(2max)
      . It is suggested that future studies address how such an approach can be adopted
      without prior knowledge of GET.

PMID- 22152078
TI  - Effect of different types of lower body resistance training on arterial
      compliance and calf blood flow.
AB  - Low-intensity resistance exercise combined with blood flow restriction has been
      shown to produce comparable increases in muscle strength and hypertrophy as
      traditional high-intensity (HI) resistance training. However, the vascular
      effects of low-intensity blood flow-restricted (LI-BFR) exercise training are not
      well characterized. Therefore, the purpose of this study was to compare the
      vascular effects of LI-BFR, moderate-intensity (MI), and HI resistance exercise
      training. Forty-six young men were divided into four groups: a HI, MI or LI-BFR
      lower body resistance training group or a non-exercise control group (C). Blood
      pressure, arterial compliance and calf vascular conductance (CVC) were assessed
      before and after the 6-week intervention. After the intervention, CVC was
      significantly increased in the three exercise groups combined compared with C
      (47.5 +/- 3.1 versus 35.0 +/- 4.5 flow per mmHg) without any changes in arterial
      compliance in any group. These results suggest HI, MI and LI-BFR lower body
      resistance exercises increase CVC, but do not affect arterial compliance. LI-BFR
      resistance exercise may be an effective alternative to HI resistance exercise for
      improving vascular conductance for individuals unable to perform HI resistance
      exercise. As more evidence concerning the safety and efficacy of LI-BFR
      resistance exercise continues to mount, this may provide a research base for
      prescribing this type of exercise if and/or when this type of exercise becomes
      more available worldwide.

PMID- 22152079
TI  - Effects of oxygen supplementation on cerebral oxygenation during exercise in
      chronic obstructive pulmonary disease patients not entitled to long-term oxygen
      therapy.
AB  - BACKGROUND: The rate of change (Delta) in cerebral oxygenation (COx) during
      exercise is influenced by blood flow and arterial O(2) content (CaO(2)). It is
      currently unclear whether DeltaCOx would (i) be impaired during exercise in
      patients with chronic obstructive pulmonary disease (COPD) who do not fulfil the
      current criteria for long-term O(2) therapy but present with exercise-induced
      hypoxaemia and (ii) improve with hyperoxia (FIO(2) = 0.4) in this specific sub
      population. METHODS: A total of 20 non-hypercapnic men (FEV(1) = 47.2 +/- 11.5%
      pred) underwent incremental cycle ergometer exercise tests under normoxia and
      hyperoxia with DeltaCOx (fold-changes from unloaded exercise in O(2)Hb) being
      determined by near-infrared spectroscopy. Pulse oximetry assessed oxyhaemoglobin
      saturation (SpO(2)), and impedance cardiography estimated changes in cardiac
      output (DeltaQT). RESULTS: Peak work rate and DeltaCOx in normoxia were lower in
      eight O(2) 'desaturators' compared with 12 'non-desaturators' (P < 0.05). Area
      under DeltaCOx during sub-maximal exercise was closely related to SpO(2)
      decrements in 'desaturators' (r = 0.92, P < 0.01). These patients showed the
      largest improvement in peak exercise capacity with hyperoxia (P < 0.05). Despite
      a trend to lower sub-maximal DeltaQT and mean arterial pressure with active
      intervention, DeltaCOx was significantly improved only in this group (0.57 +/-
      0.20 versus 2.09 +/- 0.42 for 'non-desaturators' and 'desaturators',
      respectively; P < 0.05). CONCLUSIONS: DeltaCOx was impaired in non-hypoxaemic
      patients with COPD who desaturated during exercise. Hyperoxic breathing was able
      to correct for these abnormalities, an effect related to enhanced CaO(2) rather
      than improved central haemodynamics. This indicates that O(2) supplementation
      ameliorates exercise COx in patients with COPD who are not currently entitled to
      ambulatory O(2) therapy.

PMID- 22152080
TI  - Cerebrovascular responses to cold pressor test during static exercise in humans.
AB  - The purpose of this study was to determine whether exercise modulates the
      responses of middle cerebral artery blood velocity (MCA V(mean)) and
      cerebrovascular conductance to sympathetic stimulation (i.e. cold pressor test-
      CPT). To accomplish this, MCA V(mean) responses were assessed during CPT, static
      handgrip exercise (HG) at 30% of maximum voluntary contraction and combined
      condition (HG + CPT), assigned in a counterbalanced order, in eight healthy
      subjects. Blood pressure (BP), cardiac output (CO) and end-tidal partial pressure
      of carbon dioxide (PETCO(2)) were also measured non-invasively, and an index of
      vascular conductance was calculated for MCA (CVCi). BP increased from rest (P <
      0.05) during CPT and HG and was additionally augmented during HG + CPT (P < 0.05
      versus rest, CPT and HG). Despite the greater augmentation in BP during HG + CPT,
      MCA V(mean) was similarly increased during both HG (18.5 +/- 2%, P < 0.05 versus
      rest) and combined condition (19.6 +/- 2%, P < 0.05 versus rest). MCA V(mean)
      remained unchanged from rest during CPT only. CVCi was slightly reduced (P <
      0.05) from rest during HG but was greatly reduced by CPT (P < 0.05 versus rest).
      The reduction in CVCi evoked by CPT at rest (-15 +/- 2%, P < 0.05 versus rest)
      was significantly attenuated during HG (-8 +/- 2%, P < 0.05 versus CPT).
      Increases in CO were similar in all trials, and PETCO(2) was unchanged from rest
      throughout the experiments. In summary, the cerebral conductance index decreases
      during the cold pressure test while that reduction is smaller when the CPT is
      conducted during the HG. This was critical for the maintenance of MCA V(mean)
      during combined condition.

PMID- 22152081
TI  - Reliability of ultrasonographic measurement of the architecture of the vastus
      lateralis and gastrocnemius medialis muscles in older adults.
AB  - OBJECTIVE: To determine the test-retest reliability of measurements of thickness,
      fascicle length (L(f)) and pennation angle (theta) of the vastus lateralis (VL)
      and gastrocnemius medialis (GM) muscles in older adults. PARTICIPANTS: Twenty-one
      healthy older adults (11 men and ten women; average age 68.1 +/- 5.2 years)
      participated in this study. METHODS: Ultrasound images (probe frequency 10 MHz)
      of the VL at two sites (VL site 1 and 2) were obtained with participants seated
      with knee at 90o flexion. For GM measures, participants lay prone with ankle
      fixed at 15o dorsiflexion. Measures were taken on two separate occasions, 7 days
      apart (T1 and T2). RESULTS: The ICCs (95% CI) were: VL site 1 thickness = 0.96
      (0.90-0.98); VL site 2 thickness = 0.96 (0.90-0.98), VL theta = 0.87 (0.68-0.95),
      VL L(f) = 0.80 (0.50-0.92), GM thickness = 0.97 (0.92-0.99), GM theta = 0.85
      (0.62-0.94) and GM L(f) = 0.90 (0.75-0.96). The 95% ratio limits of agreement
      (LOAs) for all measures, calculated by multiplying the standard deviation of the
      ratio of the results between T1 and T2 by 1.96, ranged from 10.59 to 38.01%.
      CONCLUSION: The ability of these tests to determine a real change in VL and GM
      muscle architecture is good on a group level but problematic on an individual
      level as the relatively large 95% ratio LOAs in the current study may encompass
      the changes in architecture observed in other training studies. Therefore, the
      current findings suggest that B-mode ultrasonography can be used with confidence
      by researchers when investigating changes in muscle architecture in groups of
      older adults, but its use is limited in showing changes in individuals over time.

PMID- 22152082
TI  - Inhalation of LPS induces inflammatory airway responses mimicking characteristics
      of chronic obstructive pulmonary disease.
AB  - AIM: Inhalation of lipopolysaccharide (LPS) produces both systemic and pulmonary
      inflammatory responses. The aim of this study was to further characterize the
      response to LPS in order to develop a human model suitable for early testing of
      drug candidates developed for the treatment for chronic obstructive pulmonary
      disease (COPD). MATERIALS: Blood and induced sputum were obtained 4, 24 and 48 h
      following inhalation of saline and LPS (5 and 50 MUg). Blood was analysed for C
      reactive protein (CRP), alpha(1)-antitrypsin and neutrophils/leucocytes, and
      sputum was analysed for biomarkers of neutrophil inflammation and remodelling
      activities, i.e. neutrophil elastase (NE) protein/activity and alpha(1)
      antitrypsin. Levels of tumour necrosis factor-alpha (TNFalpha) were measured in
      both blood and sputum. Urine was collected 0-24 and 24-48 h postchallenge, and
      desmosine, a biomarker of elastin degradation, was measured. RESULTS:
      Lipopolysaccharide inhalation induced dose-dependent flu-like symptoms and
      increases in plasma CRP and alpha(1)-antitrypsin as well as increases in blood
      neutrophil/leucocyte numbers. Furthermore, LPS produced increases in sputum
      TNFalpha and sputum NE activity. Urine levels of desmosine were unaffected by the
      LPS challenge. All subjects recovered 48 h postchallenge, and indices of
      inflammatory activity were significantly lower at this observation point cf 24 h
      postchallenge. CONCLUSION: Inhalation of LPS in healthy volunteers can be used as
      a safe and stable model of neutrophil inflammation. Blood/plasma and sputum
      indices can be employed to monitor the response to LPS. We suggest that this
      model may be used for initial human studies of novel COPD-active drugs.

PMID- 22152083
TI  - Blood flow-restricted walking does not result in an accumulation of metabolites.
AB  - The American College of Sports Medicine recommends lifting a weight of at least
      70% of one's concentric one repetition maximum to achieve muscular hypertrophy as
      it is believed that anything below this intensity does not produce significant
      muscle growth. Recent studies have found muscle hypertrophy to occur with low
      intensity 'aerobic-like' exercise with the application of blood flow restriction
      (BFR) to the limbs. Previous research with low load resistance training has shown
      that elastic knee wraps provide a practical means to induce elevations in whole
      blood lactate (WBL), which has been hypothesized to result in many of the
      adaptations observed with this type of exercise. However, this has yet to be
      investigated with low-intensity walking. Thus, the purpose of this paper was to
      determine the degree to which WBL increases with practical BFR walking. Exercise
      consisted of five 2-min bouts of walking at 75 m per min on a motor-driven
      treadmill with a 1-min rest period following each exercise bout. Participants
      completed the walking with (BFR) and without [control (CON)] restriction to the
      upper thigh in a randomized order. Practical BFR with elastic knee wraps did
      statistically increase WBL compared with CON; however, this was not considered a
      real change because the minimal difference between conditions was not exceeded.
      In conclusion, metabolic stress is not increased following practical BFR walking
      exercise. This study may provide an explanation for the lower hormone response
      observed with BFR walking and provide further evidence that mechanisms other than
      metabolic accumulation exist with BFR.

PMID- 22152084
TI  - Consistency-based detection of potential tumor-specific deletions in matched
      normal/tumor genomes.
AB  - BACKGROUND: Structural variations in human genomes, such as insertions, deletion,
      or rearrangements, play an important role in cancer development. Next-Generation
      Sequencing technologies have been central in providing ways to detect such
      variations. Most existing methods however are limited to the analysis of a single
      genome, and it is only recently that the comparison of closely related genomes
      has been considered. In particular, a few recent works considered the analysis of
      data sets obtained by sequencing both tumor and healthy tissues of the same
      cancer patient. In that context, the goal is to detect variations that are
      specific to exactly one of the genomes, for example to differentiate between
      patient-specific and tumor-specific variations. This is a difficult task,
      especially when facing the additional challenge of the possible contamination of
      healthy tissues by tumor cells and conversely. RESULTS: In the current work, we
      analyzed a data set of paired-end short-reads, obtained by sequencing tumor
      tissues and healthy tissues, both from the same cancer patient. Based on a
      combinatorial notion of conflict between deletions, we show that in the tumor
      data, more deletions are predicted than there could actually be in a diploid
      genome. In contrast, the predictions for the data from normal tissues are almost
      conflict-free. We designed and applied a method, specific to the analysis of such
      pooled and contaminated data sets, to detect potential tumor-specific deletions.
      Our method takes the deletion calls from both data sets and assigns reads from
      the mixed tumor/normal data to the normal one with the goal to minimize the
      number of reads that need to be discarded to obtain a set of conflict-free
      deletion clusters. We observed that, on the specific data set we analyze, only a
      very small fraction of the reads needs to be discarded to obtain a set of
      consistent deletions. CONCLUSIONS: We present a framework based on a rigorous
      definition of consistency between deletions and the assumption that the tumor
      sample also contains normal cells. A combined analysis of both data sets based on
      this model allowed a consistent explanation of almost all data, providing a
      detailed picture of candidate patient- and tumor-specific deletions.

PMID- 22152085
TI  - The combination of depressive symptoms and smoking shorten life expectancy among
      the aged.
AB  - BACKGROUND: Depression is a potential risk factor for mortality among the aged
      and it is also associated with other chronic diseases and unhealthy lifestyles
      that may also affect mortality. The purpose of this study was to investigate the
      association between depressive symptoms and mortality, controlling for health,
      nutritional status, and life-style factors. METHODS: A cohort of elderly people
      (N = 167) was followed-up for ten years. Information on socio-demographic
      characteristics, medical history, smoking, and alcohol consumption was collected.
      The primary outcome was all-cause mortality; the secondary outcome was cancer
      specific mortality. The Geriatric Depression Scale (GDS-15) was used to assess
      depression. Using a multivariable Cox proportional hazards regression, we
      examined the association between depressive symptoms and mortality. RESULTS:
      Elderly people with depression (scoring above the depression cut-off of 7) had a
      53% increased risk of mortality (relative risk (RR) 1.53; 95%CI: 1.05-2.24)
      compared to non-depressed subjects. The combination of depressive symptoms with
      smoking was associated with a particularly higher risk of mortality (RR: 2.61;
      95%CI: 1.28-5.31), after controlling for potential confounders. CONCLUSIONS:
      Depressive symptoms are associated with a significantly increased risk of all
      cause mortality. The combination of depressive symptoms and smoking shorten life
      expectancy among the aged.

PMID- 22152086
TI  - Year in review 2010: Critical Care--Cardiology.
AB  - We review key research papers in cardiology and intensive care published during
      2010 in Critical Care and quote related studies published in other journals if
      appropriate. Papers were grouped into the following categories: cardiovascular
      therapies, biomarkers, hemodynamic monitoring, cardiovascular diseases, and
      microcirculation.

PMID- 22152087
TI  - Effect of prolonged standardized bed rest on cystatin C and other markers of
      cardiovascular risk.
AB  - BACKGROUND: Sedentary lifestyle is associated with coronary artery disease but
      even shorter periods of physical inactivity may increase cardiovascular risk.
      Cystatin C is independently associated with cardiovascular disease and our
      objective was to investigate the relation between this novel biomarker and
      standardized bed rest. Research of immobilization physiology in humans is
      challenging because good biological models are in short supply. From the Women
      International Space simulation for Exploration study (WISE) we studied markers of
      atherosclerosis and kidney function, including cystatin C, in a standardized bed
      rest study on healthy volunteers. Fifteen healthy female volunteers participated
      in a 20-day ambulatory control period followed by 60 days of bed rest in head
      down tilt position (-6 degrees ) 24 h a day, finalized by 20 days of recovery.
      The subjects were randomized into two groups during bed rest: a control group (n
      = 8) that remained physically inactive and an exercise group (n = 7) that
      participated in both supine resistance and aerobic exercise training. RESULTS:
      Compared to baseline values there was a statistically significant increase in
      cystatin C in both groups after bed rest (P < 0.001). Glomerular filtration rate
      (GFR), calculated by both cystatin C and Cockcroft-Gault equation, decreased
      after bed rest while there were no differences in creatinine or creatine kinase
      levels. CRP did not change during bed rest in the exercise group, but there was
      an increase of CRP in the control group during recovery compared to both the
      baseline and the bed rest periods. The apo-B/apo-Ai ratio increased during bed
      rest and decreased again in the recovery period. Subjects experienced a small but
      statistically significant reduction in weight during bed rest and compared to
      baseline weights remained lower at day 8 of recovery. CONCLUSION: During and
      following prolonged standardized bed rest the concentrations of several
      clinically relevant cardiovascular risk markers change.

PMID- 22152088
TI  - Effect of Turkish propolis extracts on proteome of prostate cancer cell line.
AB  - BACKGROUND: Propolis is a natural, resinous hive product that has several
      pharmacological activities. Its composition varies depending on the vegetation,
      climate, season and environmental conditions of the area from where it was
      collected. Surface enhanced laser desorption ionization time of flight mass
      spectrometry (SELDI-TOF MS) is a proteomic approach which has been used in cancer
      proteomics studies. Prostate cancer is one of the most commonly diagnosed cancers
      in men. It has shown that nutritional supplements rich in polyphenolic compounds
      such as propolis play a significant role in prostate cancer chemoprevention. The
      aim of this study is to evaluate if protein expression profile in PC-3 prostate
      cancer cell lines could be differentiated when incubated with dimethyl sulfoxide
      and water extracts of Turkish propolis. RESULTS: The antioxidant potentials of
      dimethyl sulfoxide and water extracts of propolis were found in correlation with
      the amount of total phenolic compounds of them. Dimethyl sulfoxide and water
      extracts of propolis of 20 MUg/mL reduced the cell viability to 24.5% and 17.7%,
      respectively. Statistically significant discriminatory peaks between control PC-3
      cells and dimethyl sulfoxide extract of propolis-treated PC-3 cells were found to
      be the proteomic features at m/z 5143, 8703, 12661, 20184 and 32794, detected by
      CM10 ProteinChip, and the peak at m/z 3772, detected by Q10 ProteinChip. Between
      control PC-3 cells and water extract of propolis-treated PC-3 cells,
      statistically significant discriminatory peaks were found to be the proteomic
      features at m/z 15846, 16052 and 24658, detected by CM10 ProteinChip and the
      peaks at m/z 10348, 10899 and 11603, detected by Q10 ProteinChip. CONCLUSIONS: It
      was concluded that dimethyl sulfoxide and water extracts of Turkish propolis may
      have anti-proliferative activity through differentiating protein expression
      profile in PC-3 prostate cancer cell lines along with their antioxidant capacity.

PMID- 22152089
TI  - Efficacy and onset of action of mometasone furoate/formoterol and fluticasone
      propionate/salmeterol combination treatment in subjects with persistent asthma.
AB  - BACKGROUND: Mometasone furoate/formoterol (MF/F) is a novel combination therapy
      for treatment of persistent asthma. This noninferiority trial compared the
      effects of MF/F and fluticasone propionate/salmeterol (FP/S) combination
      therapies on pulmonary function and onset of action in subjects with persistent
      asthma. METHODS: Following a 2- to 4-week run-in period with MF administered via
      a metered-dose inhaler (MDI) 200 MUg (delivered as 2 inhalations of MF-MDI 100
      MUg) twice daily (BID), subjects (aged >=12 y) were randomized to MF/F-MDI 200/10
      MUg BID (delivered as 2 inhalations of MF/F-MDI 100/5 MUg) or FP/S administered
      via a dry powder inhaler (DPI) 250/50 MUg (delivered as 1 inhalation) BID for 12
      weeks. The primary assessment was change from baseline to week 12 in area under
      the curve for forced expiratory volume in 1 second measured serially for 0-12
      hours postdose (FEV1 AUC0-12 h). Secondary assessments included onset of action
      (change from baseline in FEV1 at 5 minutes postdose on day 1) and patient
      reported outcomes. RESULTS: 722 subjects were randomized to MF/F-MDI (n = 371) or
      FP/S-DPI (n = 351). Mean FEV1 AUC0-12 h change from baseline at week 12 for MF/F
      MDI and FP/S-DPI was 3.43 and 3.24 L * h, respectively (95% CI, -0.40 to 0.76).
      MF/F-MDI was associated with a 200-mL mean increase from baseline in FEV1 at 5
      minutes postdose on day 1, which was significantly larger than the 90-mL increase
      for FP/S-DPI (P < 0.001). The overall incidence of adverse events during the 12
      week treatment period that were considered related to study therapy was similar
      in both groups (MF/F-MDI, 7.8% [n = 29]; FP/S-DPI, 8.3% [n = 29]). CONCLUSIONS:
      The results of this 12-week study indicated that MF/F improves pulmonary function
      and asthma control similar to FP/S with a superior onset of action compared with
      FP/S. Both drugs were safe, improved asthma control, and demonstrated similar
      results for other secondary study endpoints. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00424008.

PMID- 22152090
TI  - Optimized deconvolution for maximum axial resolution in three-dimensional
      aberration-corrected scanning transmission electron microscopy.
AB  - Three-dimensional (3D) datasets were recorded of gold nanoparticles placed on
      both sides of silicon nitride membranes using focal series aberration-corrected
      scanning transmission electron microscopy (STEM). Deconvolution of the 3D
      datasets was applied to obtain the highest possible axial resolution. The
      deconvolution involved two different point spread functions, each calculated
      iteratively via blind deconvolution. Supporting membranes of different
      thicknesses were tested to study the effect of beam broadening on the
      deconvolution. It was found that several iterations of deconvolution was
      efficient in reducing the imaging noise. With an increasing number of iterations,
      the axial resolution was increased, and most of the structural information was
      preserved. Additional iterations improved the axial resolution by maximal a
      factor of 4 to 6, depending on the particular dataset, and up to 8 nm maximal,
      but also led to a reduction of the lateral size of the nanoparticles in the
      image. Thus, the deconvolution procedure optimized for the highest axial
      resolution is best suited for applications where one is interested in the 3D
      locations of nanoparticles only.

PMID- 22152091
TI  - Synthesis and application of polyaminoamide as new paraffin inhibitor from
      vegetable oil.
AB  - In this work, a series of novel paraffin inhibitor, polyaminoamide (PAA), was
      designed and prepared by aminolysis and poly-condensation using soybean oil and
      canola oil as the raw material. The property of the PAAs as paraffin inhibitor
      was investigated, the results show several PAA samples are potent in paraffin
      inhibition, and PPC-2 is the most effective one. Besides, the paraffin crystal
      morphology analysis was carried out to provide the mechanism of paraffin
      inhibition.

PMID- 22152092
TI  - Beneficial effects of ginger (Zingiber officinale) on carbohydrate metabolism in
      streptozotocin-induced diabetic rats.
AB  - Zingiber officinale (ZO), commonly known as ginger, has been traditionally used
      in the treatment of diabetes mellitus. Several studies have reported the
      hypoglycaemic properties of ginger in animal models. The present study evaluated
      the antihyperglycaemic effect of its aqueous extract administered orally (daily)
      in three different doses (100, 300, 500 mg/kg body weight) for a period of 30 d
      to streptozotocin (STZ)-induced diabetic rats. A dose-dependent
      antihyperglycaemic effect revealed a decrease of plasma glucose levels by 38 and
      68 % on the 15th and 30th day, respectively, after the rats were given 500 mg/kg.
      The 500 mg/kg ZO significantly (P<0.05) decreased kidney weight (% body weight)
      in ZO-treated diabetic rats v. control rats, although the decrease in liver
      weight (% body weight) was not statistically significant. Kidney glycogen content
      increased significantly (P<0.05) while liver and skeletal muscle glycogen content
      decreased significantly (P<0.05) in diabetic controls v. normal controls. ZO (500
      mg/kg) also significantly decreased kidney glycogen (P<0.05) and increased liver
      and skeletal muscle glycogen in STZ-diabetic rats when compared to diabetic
      controls. Activities of glucokinase, phosphofructokinase and pyruvate kinase in
      diabetic controls were decreased by 94, 53 and 61 %, respectively, when compared
      to normal controls; and ZO significantly increased (P<0.05) those enzymes'
      activities in STZ-diabetic rats. Therefore, the present study showed that ginger
      is a potential phytomedicine for the treatment of diabetes through its effects on
      the activities of glycolytic enzymes.

PMID- 22152093
TI  - Human herpesvirus 6A induces apoptosis of primary human fetal astrocytes via both
      caspase-dependent and -independent pathways.
AB  - BACKGROUND: Human herpesvirus 6 (HHV-6) is a T-lymphtropic and neurotropic virus
      that can infect various types of cells. Sequential studies reported that
      apoptosis of glia and neurons induced by HHV-6 might act a potential trigger for
      some central nervous system (CNS) diseases. HHV-6 is involved in the pathogenesis
      of encephalitis, multiple sclerosis (MS) and fatigue syndrome. However, the
      mechanisms responsible for the apoptosis of infected CNS cells induced by HHV-6
      are poorly understood. In this study, we investigated the cell death processes of
      primary human fetal astrocytes (PHFAs) during productive HHV-6A infection and the
      underlying mechanisms. RESULTS: HHV-6A can cause productive infection in primary
      human fetal astrocytes. Annexin V-PI staining and electron microscopic analysis
      indicated that HHV-6A was an inducer of apoptosis. The cell death was associated
      with activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP),
      which is known to be an important substrate for activated caspase-3. Caspase-8
      and -9 were also significantly activated in HHV-6A-infected cells. Moreover, HHV
      6A infection led to Bax up-regulation and Bcl-2 down-regulation. HHV-6A infection
      increased the release of Smac/Diablo, AIF and cytochrome c from mitochondria to
      cytosol, which induced apoptosis via the caspase-dependent and -independent
      pathways. In addition, we also found that anti-apoptotic factors such as IAPs and
      NF-kappaB decreased in HHV-6A infected PHFAs. CONCLUSION: This is the first
      demonstration of caspase-dependent and -independent apoptosis in HHV-6A-infected
      glial cells. These findings would be helpful in understanding the mechanisms of
      CNS diseases caused by HHV-6.

PMID- 22152094
TI  - Poor quality vital anti-malarials in Africa - an urgent neglected public health
      priority.
AB  - BACKGROUND: Plasmodium falciparum malaria remains a major public health problem.
      A vital component of malaria control rests on the availability of good quality
      artemisinin-derivative based combination therapy (ACT) at the correct dose.
      However, there are increasing reports of poor quality anti-malarials in Africa.
      METHODS: Seven collections of artemisinin derivative monotherapies, ACT and
      halofantrine anti-malarials of suspicious quality were collected in 2002/10 in
      eleven African countries and in Asia en route to Africa. Packaging, chemical
      composition (high performance liquid chromatography, direct ionization mass
      spectrometry, X-ray diffractometry, stable isotope analysis) and botanical
      investigations were performed. RESULTS: Counterfeit artesunate containing
      chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol
      (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit
      artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine
      containing artemisinin, and substandard/counterfeit or degraded artesunate and
      artesunate+amodiaquine in eight countries are described. Pollen analysis was
      consistent with manufacture of counterfeits in eastern Asia. These data do not
      allow estimation of the frequency of poor quality anti-malarials in Africa.
      CONCLUSIONS: Criminals are producing diverse harmful anti-malarial counterfeits
      with important public health consequences. The presence of artesunate
      monotherapy, substandard and/or degraded and counterfeit medicines containing sub
      therapeutic amounts of unexpected anti-malarials will engender drug resistance.
      With the threatening spread of artemisinin resistance to Africa, much greater
      investment is required to ensure the quality of ACTs and removal of artemisinin
      monotherapies. The International Health Regulations may need to be invoked to
      counter these serious public health problems.

PMID- 22152096
TI  - A novel machine-vision-based facility for the automatic evaluation of yield
      related traits in rice.
AB  - The evaluation of yield-related traits is an essential step in rice breeding,
      genetic research and functional genomics research. A new, automatic, and labor
      free facility to automatically thresh rice panicles, evaluate rice yield traits,
      and subsequently pack filled spikelets is presented in this paper. Tests showed
      that the facility was capable of evaluating yield-related traits with a mean
      absolute percentage error of less than 5% and an efficiency of 1440 plants per
      continuous 24 h workday.

PMID- 22152095
TI  - Genome-wide analytical approaches for reverse metabolic engineering of
      industrially relevant phenotypes in yeast.
AB  - Successful reverse engineering of mutants that have been obtained by nontargeted
      strain improvement has long presented a major challenge in yeast biotechnology.
      This paper reviews the use of genome-wide approaches for analysis of
      Saccharomyces cerevisiae strains originating from evolutionary engineering or
      random mutagenesis. On the basis of an evaluation of the strengths and weaknesses
      of different methods, we conclude that for the initial identification of relevant
      genetic changes, whole genome sequencing is superior to other analytical
      techniques, such as transcriptome, metabolome, proteome, or array-based genome
      analysis. Key advantages of this technique over gene expression analysis include
      the independency of genome sequences on experimental context and the possibility
      to directly and precisely reproduce the identified changes in naive strains. The
      predictive value of genome-wide analysis of strains with industrially relevant
      characteristics can be further improved by classical genetics or simultaneous
      analysis of strains derived from parallel, independent strain improvement
      lineages.

PMID- 22152098
TI  - A short-chain methotrexate polyglutamate as outcome parameter in rheumatoid
      arthritis patients receiving methotrexate.
AB  - OBJECTIVES: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid
      arthritis (RA). Although in general MTX is very effective, the major drawback is
      the large inter-patient variability in clinical response. The circulating levels
      of MTX polyglutamates (MTXPGs) are supposed to correlate with clinical efficacy,
      therefore having a potential role in drug monitoring. However, there is a
      controversial discussion about the importance of methotrexate polyglutamates as
      outcome parameters in the therapy of rheumatoid arthritis. The aim of the present
      study was to investigate the formation and pharmacokinetics of MTXPGs and to
      correlate their concentration with clinical response in MTX-naive patients.
      METHODS: The pharmacokinetics of erythrocyte MTXPGs was determined in samples of
      nineteen MTX-naive patients by high pressure liquid chromatography (HPLC) using
      post-column photo-oxidation and fluorimetric detection. The relationship between
      erythrocyte concentrations of MTXPGs and the primary outcome parameter DAS-28 was
      assessed using the Spearman's correlation coefficient. RESULTS: The short-chain
      polyglutamate MTXPG2 revealed to be a potential marker for clinical outcome in
      rheumatoid arthritis with a statistically significant positive correlation of
      MTXPG2 Cmax levels and improvement in DAS-28 (+0.518, p=0.023) over 16 weeks.
      Furthermore, Cmax levels of MTXPG2 negatively correlated with basophils (-0.478,
      p=0.038) and eosinophils (-0.531, p=0.019), both pro-inflammatory cells involved
      in the disease. CONCLUSIONS: MTXPG2 seems to be a potential indicator for
      clinical response and may serve as a marker for drug monitoring.

PMID- 22152097
TI  - Differentiation of breast cancer stem cells by knockdown of CD44: promising
      differentiation therapy.
AB  - BACKGROUND: Breast cancer stem cells (BCSCs) are the source of breast tumors.
      Compared with other cancer cells, cancer stem cells show high resistance to both
      chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising
      and effective strategy for breast cancer treatment. Differentiation therapy
      represents one type of cancer stem-cell-targeting therapy, aimed at attacking the
      stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In
      a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the
      anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown
      caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs).
      METHODS: We isolated a breast cancer cell population (CD44+CD24- cells) from
      primary cultures of malignant breast tumors. These cells were sorted into four
      sub-populations based on their expression of CD44 and CD24 surface markers. CD44
      knockdown in the BCSC population was achieved using small hairpin RNA lentivirus
      particles. The differentiated status of CD44 knock-down BCSCs was evaluated on
      the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and
      gene expression in relation to renewal status, metastasis, and cell cycle in
      comparison with BCSCs and non-BCSCs. RESULTS: Knockdown of CD44 caused BCSCs to
      differentiate into non-BCSCs with lower tumorigenic potential, and altered the
      cell cycle and expression profiles of some stem cell-related genes, making them
      more similar to those seen in non-BCSCs. CONCLUSIONS: Knockdown of CD44 is an
      effective strategy for attacking the stemness of BCSCs, resulting in a loss of
      stemness and an increase in susceptibility to chemotherapy or radiation. The
      results of this study highlight a potential new strategy for breast cancer
      treatment through the targeting of BCSCs.

PMID- 22152099
TI  - Negative ion treatment increases positive emotional processing in seasonal
      affective disorder.
AB  - BACKGROUND: Antidepressant drug treatments increase the processing of positive
      compared to negative affective information early in treatment. Such effects have
      been hypothesized to play a key role in the development of later therapeutic
      responses to treatment. However, it is unknown whether these effects are a common
      mechanism of action for different treatment modalities. High-density negative ion
      (HDNI) treatment is an environmental manipulation that has efficacy in randomized
      clinical trials in seasonal affective disorder (SAD). METHOD: The current study
      investigated whether a single session of HDNI treatment could reverse negative
      affective biases seen in seasonal depression using a battery of emotional
      processing tasks in a double-blind, placebo-controlled randomized study. RESULTS:
      Under placebo conditions, participants with seasonal mood disturbance showed
      reduced recognition of happy facial expressions, increased recognition memory for
      negative personality characteristics and increased vigilance to masked
      presentation of negative words in a dot-probe task compared to matched healthy
      controls. Negative ion treatment increased the recognition of positive compared
      to negative facial expression and improved vigilance to unmasked stimuli across
      participants with seasonal depression and healthy controls. Negative ion
      treatment also improved recognition memory for positive information in the SAD
      group alone. These effects were seen in the absence of changes in subjective
      state or mood. CONCLUSIONS: These results are consistent with the hypothesis that
      early change in emotional processing may be an important mechanism for treatment
      action in depression and suggest that these effects are also apparent with
      negative ion treatment in seasonal depression.

PMID- 22152100
TI  - Baclofen alters gustatory discrimination capabilities and induces a conditioned
      taste aversion (CTA).
AB  - BACKGROUND: Studies intending to measure drug-induced changes in learning and
      memory are challenged to parse out the effects of drugs on sensory, motor, and
      associative systems in the brain. In the context of conditioned taste aversion
      (CTA), drugs that alter the sensorium of subjects and affect their ability to
      taste and/or feel malaise may limit the ability of investigators to make
      conclusions about associative effects of these substances. Since the GABAergic
      system is implicated in inhibition, the authors were hopeful to use the GABA
      agonist, baclofen (BAC), to enhance extinction of a CTA, but first a preliminary
      evaluation of BAC's peripheral effects on animals' sensorium had to be completed
      due to a lack of published literature in this area. FINDINGS: Our first
      experiment aimed to evaluate the extent to which the GABAB agonist, BAC, altered
      the ability of rats to differentiate between 0.3% and 0.6% saccharin (SAC) in a
      two bottle preference test. Here we report that 2 or 3 mg/kg (i.p.) BAC, but not
      1 mg/kg BAC, impaired animals' gustatory discrimination abilities in this task.
      Furthermore, when SAC consumption was preceded by 2 or 3 mg/kg (i.p.) BAC, rats
      depressed their subsequent SAC drinking.A second experiment evaluated if the
      suppression of SAC and water drinking (revealed in Experiment 1) was mediated by
      amnesiac effects of BAC or whether BAC possessed US properties in the context of
      the CTA paradigm. The time necessary to reach an asymptotic level of CTA
      extinction was not significantly different in those animals that received the 3
      mg/kg dose of BAC compared to more conventionally SAC + lithium chloride (LiCl,
      81 mg/kg) conditioned animals. CONCLUSIONS: Our findings were not consistent with
      a simple amnesia-of-neophobia explanation. Instead, results indicated that 2 and
      3 mg/kg (i.p.) BAC were capable of inducing a CTA, which was extinguishable via
      repeated presentations of SAC only. Our data indicate that, depending on the
      dose, BAC can alter SAC taste discrimination and act as a potent US in the
      context of a CTA paradigm.

PMID- 22152102
TI  - Longstanding tracheobronchial foreign body in an adult.

PMID- 22152101
TI  - Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in
      first-line metastatic gastric and oesophago-gastric junction cancer: results from
      a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
AB  - BACKGROUND: The activity of the epidermal growth factor receptor (EGFR)-directed
      monoclonal antibody cetuximab combined with oxaliplatin/leucovorin/5-fluorouracil
      (FUFOX) was assessed in first-line metastatic gastric and oesophago-gastric
      junction (OGJ) cancer in a prospective phase II study showing a promising
      objective tumour response rate of 65% and a low mutation frequency of KRAS (3%).
      The aim of the correlative tumour tissue studies was to investigate the
      relationship between EGFR gene copy numbers, activation of the EGFR pathway,
      expression and mutation of E-cadherin, V600E BRAF mutation and clinical outcome
      of patients with gastric and OGJ cancer treated with cetuximab combined with
      FUFOX. METHODS: Patients included in this correlative study (n = 39) were a
      subset of patients from the clinical phase II study. The association between EGFR
      gene copy number, activation of the EGFR pathway, abundance and mutation of E
      cadherin which plays an important role in these disorders, BRAF mutation and
      clinical outcome of patients was studied. EGFR gene copy number was assessed by
      FISH. Expression of the phosphorylated forms of EGFR and its downstream effectors
      Akt and MAPK, in addition to E-cadherin was analysed by immunohistochemistry. The
      frequency of mutant V600E BRAF was evaluated by allele-specific PCR and the
      mutation profile of the E-cadherin gene CDH1 was examined by DHPLC followed by
      direct sequence analysis. Correlations with overall survival (OS), time to
      progression (TTP) and overall response rate (ORR) were assessed. RESULTS: Our
      study showed a significant association between increased EGFR gene copy number
      (>= 4.0) and OS in gastric and OGJ cancer, indicating the possibility that
      patients may be selected for treatment on a genetic basis. Furthermore, a
      significant correlation was shown between activated EGFR and shorter TTP and ORR,
      but not between activated EGFR and OS. No V600E BRAF mutations were identified.
      On the other hand, an interesting trend between high E-cadherin expression levels
      and better OS was observed and two CDH1 exon 9 missense mutations (A408V and
      D402H) were detected. CONCLUSION: Our finding that increased EGFR gene copy
      numbers, activated EGFR and the E-cadherin status are potentially interesting
      biomarkers needs to be confirmed in larger randomized clinical trials. TRIAL
      REGISTRATION: Multicentre clinical study with the European Clinical Trials
      Database number 2004-004024-12.

PMID- 22152103
TI  - Visual Diagnosis: Pearling: a case study.
AB  - We present the case of a patient who attempted to perform a type of body
      modification known as "pearling" or "genital beading" while in prison. This
      patient unfortunately caused severe trauma to his penis, requiring surgical
      intervention. Photographs of the traumatic injuries are presented.

PMID- 22152104
TI  - New tracheal tubes to prevent ventilator-associated pneumonia: where is the
      evidence?

PMID- 22152105
TI  - The genomic features that affect the lengths of 5' untranslated regions in
      multicellular eukaryotes.
AB  - BACKGROUND: The lengths of 5'UTRs of multicellular eukaryotes have been suggested
      to be subject to stochastic changes, with upstream start codons (uAUGs) as the
      major constraint to suppress 5'UTR elongation. However, this stochastic model
      cannot fully explain the variations in 5'UTR length. We hypothesize that the
      selection pressure on a combination of genomic features is also important for
      5'UTR evolution. The ignorance of these features may have limited the explanatory
      power of the stochastic model. Furthermore, different selective constraints
      between vertebrates and invertebrates may lead to differences in the determinants
      of 5'UTR length, which have not been systematically analyzed. METHODS: Here we
      use a multiple linear regression model to delineate the correlation between 5'UTR
      length and the combination of a series of genomic features (G+C content, observed
      to-expected (OE) ratios of uAUGs, upstream stop codons (uSTOPs), methylation
      related CG/UG dinucleotides, and mRNA-destabilizing UU/UA dinucleotides) in six
      vertebrates (human, mouse, rat, chicken, African clawed frog, and zebrafish) and
      four invertebrates (fruit fly, mosquito, sea squirt, and nematode). The relative
      contributions of each feature to the variation of 5'UTR length were also
      evaluated. RESULTS: We found that 14%~33% of the 5'UTR length variations can be
      explained by a linear combination of the analyzed genomic features. The most
      important genomic features are the OE ratios of uSTOPs and G+C content. The
      surprisingly large weightings of uSTOPs highlight the importance of selection on
      upstream open reading frames (which include both uAUGs and uSTOPs), rather than
      on uAUGs per se. Furthermore, G+C content is the most important determinants for
      most invertebrates, but for vertebrates its effect is second to uSTOPs. We also
      found that shorter 5'UTRs are affected more by the stochastic process, whereas
      longer 5'UTRs are affected more by selection pressure on genomic features.
      CONCLUSIONS: Our results suggest that upstream open reading frames may be the
      real target of selection, rather than uAUGs. We also show that the selective
      constraints on genomic features of 5'UTRs differ between vertebrates and
      invertebrates, and between longer and shorter 5'UTRs. A more comprehensive model
      that takes these findings into consideration is needed to better explain 5'UTR
      length evolution.

PMID- 22152106
TI  - Comparing different types of source memory attributes in dementia of Alzheimer's
      type.
AB  - BACKGROUND: Source monitoring (SM) refers to our ability to discriminate between
      memories from different sources. METHODS: Twenty healthy high-cognitive
      functioning older adults, 20 healthy low-cognitive functioning older adults, and
      20 older adults with dementia of Alzheimer's type (DAT) were asked to perform a
      series of SM tasks that varied in terms of the to-be-remembered source attribute
      (perceptual, spatial, temporal, semantic, social, and affective details).
      RESULTS: Results indicated that older DAT adults had greater difficulty in SM
      compared to the healthy control groups, especially with spatial and semantic
      details. CONCLUSIONS: Data are discussed in terms of the SM framework and suggest
      that poor memory for some types of source information may be considered as an
      important indicator of clinical memory function when assessing for the presence
      and severity of dementia.

PMID- 22152107
TI  - Health-related quality of life and self-related health in patients with type 2
      diabetes: effects of group-based rehabilitation versus individual counselling.
AB  - BACKGROUND: Type 2 diabetes can seriously affect patients' health-related quality
      of life and their self-rated health. Most often, evaluation of diabetes
      interventions assess effects on glycemic control with little consideration of
      quality of life. The aim of the current study was to study the effectiveness of
      group-based rehabilitation versus individual counselling on health-related
      quality of life (HRQOL) and self-rated health in type 2 diabetes patients.
      METHODS: We randomised 143 type 2 diabetes patients to either a six-month
      multidisciplinary group-based rehabilitation programme including patient
      education, supervised exercise and a cooking-course or a six-month individual
      counselling programme. HRQOL was measured by Medical Outcomes Study Short Form 36
      item Health Survey (SF-36) and self-rated health was measured by Diabetes Symptom
      Checklist - Revised (DCS-R). RESULTS: In both groups, the lowest estimated mean
      scores of the SF36 questionnaire at baseline were "vitality" and "general
      health". There were no significant differences in the change of any item between
      the two groups after the six-month intervention period. However, vitality-score
      increased 5.2 points (p = 0.12) within the rehabilitation group and 5.6 points (p
      = 0.03) points among individual counselling participants.In both groups, the
      highest estimated mean scores of the DSC-R questionnaire at baseline were
      "Fatigue" and "Hyperglycaemia". Hyperglycaemic and hypoglycaemic distress
      decreased significantly after individual counselling than after group-based
      rehabilitation (difference -0.3 points, p = 0.04). No between-group differences
      occurred for any other items. However, fatigue distress decreased 0.40 points
      within the rehabilitation group (p = 0.01) and 0.34 points within the individual
      counselling group (p < 0.01). In the rehabilitation group cardiovascular distress
      decreased 0.25 points (p = 0.01). CONCLUSIONS: A group-based rehabilitation
      programme did not improve health-related quality of life and self-rated health
      more than an individual counselling programme. In fact, the individual group
      experienced a significant relief in hyper- and hypoglycaemic distress compared
      with the rehabilitation group.However, the positive findings of several items in
      both groups indicate that lifestyle intervention is an important part of the
      management of type 2 diabetes patients.

PMID- 22152108
TI  - Investigating the role of c-Jun N-terminal kinases in the proliferation of Werner
      syndrome fibroblasts using diaminopyridine inhibitors.
AB  - Fibroblasts derived from the progeroid Werner syndrome show reduced replicative
      lifespan and a "stressed" morphology, both alleviated using the MAP kinase
      inhibitor SB203580. However, interpretation of these data is problematical
      because although SB203580 has the stress-activated kinases p38 and JNK1/2 as its
      preferred targets, it does show relatively low overall kinase selectivity.
      Several lines of data support a role for both p38 and JNK1/2 activation in the
      control of cellular proliferation and also the pathology of diseases of ageing,
      including type II diabetes, diseases to which Werner Syndrome individuals are
      prone, thus making the use of JNK inhibitors attractive as possible therapeutics.
      We have thus tested the effects of the widely used JNK inhibitor SP600125 on the
      proliferation and morphology of WS cells. In addition we synthesised and tested
      two recently described aminopyridine based inhibitors. SP600125 treatment
      resulted in the cessation of proliferation of WS cells and resulted in a
      senescent-like cellular phenotype that does not appear to be related to the
      inhibition of JNK1/2. In contrast, use of the more selective aminopyridine CMPD
      6o at concentrations that fully inhibit JNK1/2 had a positive effect on cellular
      proliferation of immortalised WS cells, but no effect on the replicative lifespan
      of primary WS fibroblasts. In addition, CMPD 6o corrected the stressed WS
      cellular morphology. The aminopyridine CMPD 6r, however, had little effect on WS
      cells. CMDP 6o was also found to be a weak inhibitor of MK2, which may partially
      explain its effects on WS cells, since MK2 is known to be involved in regulating
      cellular morphology via HSP27 phosphorylation, and is thought to play a role in
      cell cycle arrest. These data suggest that total JNK1/2 activity does not play a
      substantial role in the proliferation control in WS cells.

PMID- 22152109
TI  - Crimean-Congo hemorrhagic fever: epidemiological trends and controversies in
      treatment.
AB  - Crimean-Congo hemorrhagic fever (CCHF) virus has the widest geographic range of
      all tick-borne viruses and is endemic in more than 30 countries in Eurasia and
      Africa. Over the past decade, new foci have emerged or re-emerged in the Balkans
      and neighboring areas. Here we discuss the factors influencing CCHF incidence and
      focus on the main issue of the use of ribavirin for treating this infection.
      Given the dynamics of CCHF emergence in the past decade, development of new anti
      viral drugs and a vaccine is urgently needed to treat and prevent this acute,
      life-threatening disease.

PMID- 22152110
TI  - Proliferation/Quiescence: When to start? Where to stop? What to stock?
AB  - The cell cycle is a tightly controlled series of events that ultimately lead to
      cell division. The literature deciphering the molecular processes involved in
      regulating the consecutive cell cycle steps is colossal. By contrast, much less
      is known about non-dividing cellular states, even if they concern the vast
      majority of cells, from prokaryotes to multi-cellular organisms. Indeed, cells
      decide to enter the division cycle only if conditions are favourable. Otherwise
      they may enter quiescence, a reversible non-dividing cellular state. Recent
      studies in yeast have shed new light on the transition between proliferation and
      quiescence, re-questioning the notion of cell cycle commitment. They also
      indicate a predominant role for cellular metabolic status as a major regulator of
      quiescence establishment and exit. Additionally, a growing body of evidence
      indicates that environmental conditions, and notably the availability of various
      nutrients, by impinging on specific metabolic routes, directly regulate specific
      cellular re-organization that occurs upon proliferation/quiescence transitions.

PMID- 22152111
TI  - Downregulation of APOBEC3G by xenotropic murine leukemia-virus related virus
      (XMRV) in prostate cancer cells.
AB  - BACKGROUND: Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a
      gammaretrovirus that was discovered in prostate cancer tissues. Recently, it has
      been proposed that XMRV is a laboratory contaminant and may have originated via a
      rare recombination event. Host restriction factor APOBEC3G (A3G) has been
      reported to severely restrict XMRV replication in human peripheral blood
      mononuclear cells. Interestingly, XMRV infects and replicates efficiently in
      prostate cancer cells of epithelial origin. It has been proposed that due to lack
      off or very low levels of A3G protein XMRV is able to productively replicate in
      these cells. FINDINGS: This report builds on and challenges the published data on
      the absence of A3G protein in prostate epithelial cells lines. We demonstrate the
      presence of A3G in prostate epithelial cell lines (LNCaP and DU145) by western
      blot and mass spectrometry. We believe the discrepancy in A3G detection is may be
      due to selection and sensitivity of A3G antibodies employed in the prior studies.
      Our results also indicate that XMRV produced from A3G expressing LNCaP cells can
      infect and replicate in target cells. Most importantly our data reveal
      downregulation of A3G in XMRV infected LNCaP and DU145 cells. CONCLUSIONS: We
      propose that XMRV replicates efficiently in prostate epithelial cells by
      downregulating A3G expression. Given that XMRV lacks accessory proteins such as
      HIV-1 Vif that are known to counteract A3G function in human cells, our data
      suggest a novel mechanism by which retroviruses can counteract the antiviral
      effects of A3G proteins.

PMID- 22152112
TI  - Desmoplakin is important for proper cardiac cell-cell interactions.
AB  - Normal cardiac function is maintained through dynamic interactions of cardiac
      cells with each other and with the extracellular matrix. These interactions are
      important for remodeling during cardiac growth and pathophysiological conditions.
      However, the precise mechanisms of these interactions remain unclear. In this
      study we examined the importance of desmoplakin (DSP) in cardiac cell-cell
      interactions. Cell-cell communication in the heart requires the formation and
      preservation of cell contacts by cell adhesion junctions called desmosome-like
      structures. A major protein component of this complex is DSP, which plays a role
      in linking the cytoskeletal network to the plasma membrane. Our laboratory
      previously generated a polyclonal antibody (1611) against the detergent soluble
      fraction of cardiac fibroblast plasma membrane. In attempting to define which
      proteins 1611 recognizes, we performed two-dimensional electrophoresis and
      identified DSP as one of the major proteins recognized by 1611.
      Immunoprecipitation studies demonstrated that 1611 was able to directly pulldown
      DSP. We also demonstrate that 1611 and anti-DSP antibodies co-localize in whole
      heart sections. Finally, using a three-dimensional in vitro cell-cell interaction
      assay, we demonstrate that 1611 can inhibit cell-cell interactions. These data
      indicate that DSP is an important protein for cell-cell interactions and affects
      a variety of cellular functions, including cytokine secretion.

PMID- 22152113
TI  - Molecular features of the complementarity determining region 3 motif of the T
      cell population and subsets in the blood of patients with chronic severe
      hepatitis B.
AB  - BACKGROUND: T cell receptor (TCR) reflects the status and function of T cells. We
      previously developed a gene melting spectral pattern (GMSP) assay, which rapidly
      detects clonal expansion of the T cell receptor beta variable gene (TCRBV) in
      patients with HBV by using quantitative real-time reverse transcription PCR (qRT
      PCR) with DNA melting curve analysis. However, the molecular profiles of TCRBV in
      peripheral blood mononuclear cells (PBMCs) and CD8+, CD8- cell subsets from
      chronic severe hepatitis B (CSHB) patients have not been well described. METHODS:
      Human PBMCs were separated and sorted into CD8+ and CD8- cell subsets using
      density gradient centrifugation and magnetic activated cell sorting (MACS). The
      molecular features of the TCRBV CDR3 motif were determined using GMSP analysis;
      the TCRBV families were cloned and sequenced when the GMSP profile showed a
      single-peak, indicative of a monoclonal population. RESULTS: The number of skewed
      TCRBV in the CD8+ cell subset was significantly higher than that of the CD8- cell
      subset as assessed by GMSP analysis. The TCRBV11 and BV7 were expressed more
      frequently than other members of TCRBV family in PBMCs and CD8+, CD8- subsets.
      Also the relatively conserved amino acid motifs were detected in the TCRBV22,
      BV18 and BV11 CDR3 in PBMCs among patients with CSHB. CONCLUSIONS: The molecular
      features of the TCRBV CDR3 were markedly different among PBMCs and CD8+, CD8-
      cell subsets derived from CSHB patients. Analysis of the TCRBV expression in the
      CD8+ subset was more accurate in assessing the status and function of circulating
      T cells. The expression of TCRBV11, BV7 and the relatively conserved CDR3 amino
      acid motifs could also help to predict and treat patients with CSHB.

PMID- 22152114
TI  - Urinary citrulline in very low birth weight preterm infants receiving intravenous
      nutrition.
AB  - As gut immaturity precludes full enteral feeding, very low birth weight (VLBW)
      preterm infants receive parenteral nutrition (PN) during the first few weeks of
      life. Weaning VLBW infants off PN, however, is a top priority since PN is
      associated with a high risk of complications. The decision making is purely
      empirical, as there is currently no suitable index of gastrointestinal (GI)
      maturity. Plasma citrulline concentration is considered an index of GI function
      in conditions such as short-bowel syndrome and coeliac disease in adults. To
      identify the factors determining urinary citrulline excretion, and determine
      whether urinary citrulline excretion could be used as a non-invasive index of GI
      tolerance to enteral feeding, nutritional intake and urinary citrulline were
      monitored bi-weekly in forty-seven preterm infants < 1500 g (interquartiles 880
      1320 g), during their stay in the Neonatology unit. Median urinary citrulline was
      24.7 MUmol/mmol creatinine (14.5-38.6 MUmol/mmol creatinine). No relationship was
      observed with the percentage of energy tolerated enterally. In multivariate
      regression analysis, weak correlations were found with post-conceptional age (P =
      0.001), parenteral amino acid supply (P = 0.001) and the daily volume of enteral
      mixture administered (P = 0.043). A significant correlation was found with
      urinary nitrite+nitrate excretion (r 0.47; P < 0.001). We conclude that in
      preterm infants: (1) one of the major determinants of urinary citrulline may be
      the biosynthesis of citrulline from arginine by NO-synthase; (2) urinary
      citrulline cannot be used to predict GI tolerance. This is consistent with the
      observations that, in neonatal gut, citrulline is converted to arginine in situ
      rather than exported towards the kidneys as observed in adults.

PMID- 22152115
TI  - Relative validation of the KiGGS Food Frequency Questionnaire among adolescents
      in Germany.
AB  - BACKGROUND: The aim of this study was to determine the relative validity of the
      self-administered Food Frequency Questionnaire (FFQ) "What do you eat?", which
      was used in the German National Health Interview and Examination Survey for
      Children and Adolescents (KiGGS 2003-2006). METHODS: The validation was conducted
      in the EsKiMo Nutrition Module, a subsample of KiGGS. The study population
      included 1,213 adolescents aged between 12 and 17. A modified diet history
      interview DISHES (Dietary Interview Software for Health Examination Studies) was
      used as the reference method. In order to compare the food groups, the data
      assessed with both instruments were aggregated to 40 similar food groups. The
      statistical analysis included calculating and comparing Spearman's correlation
      coefficients, calculating the mean difference between both methods, and ranking
      participants (quartiles) according to food group consumption, including weighted
      kappa coefficients. Correlations were also evaluated for relative body weight and
      socioeconomic status subgroups. RESULTS: In the total study population the
      Spearman correlation coefficients ranged from 0.22 for pasta/rice to 0.69 for
      margarine; most values were 0.50 and higher. The mean difference ranged between
      1.4% for milk and 100.3% for pasta/rice. The 2.5 percentiles and 97.5 percentiles
      indicated a wide range of differences. Classifications in the same and adjacent
      quartile varied between 70.1% for pasta/rice and 90.8% for coffee. For most
      groups, Cohen's weighted kappa showed values between 0.21 and 0.60. Only for
      white bread and pasta/rice were values less than 0.20. Most of the 40 food groups
      showed acceptable to good correlations in all investigated subgroups concerning
      age, sex, body weight and socio-economic status. CONCLUSIONS: The KiGGS FFQ
      showed fair to moderate ranking validity except for pasta/rice and white bread.
      However, the ability to assess absolute intakes is limited. The correlation
      coefficients for most food items were similar for normal weight and overweight as
      well as for different socio-economic status groups. Overall, the results of the
      relative validity were comparable to FFQs from the current literature.

PMID- 22152116
TI  - Rheumatoid arthritis in Cardinal Carlo de' Medici (1595-1666): a confirmed
      macroscopic, radiologic and molecular diagnosis.
AB  - OBJECTIVES: The paleopathological study of the skeletal remains belonging to
      Cardinal Carlo de' Medici (1595-1666), son of Ferdinando I (1549-1609) and
      Cristina of Lorena (1565-1637), has been presented previously. A diagnosis of
      Klippel-Feil syndrome, tuberculosis and a polyarthopathy, interpreted as
      rheumatoid arthritis, was suggested. A revision of this case based on the
      analysis of the historical documents and of some radiological images of Carlo's
      bones has been proposed recently; according to the Authors, the Cardinal was
      affected by the 'Medici syndrome', a combined Psoriatic-DISH arthropathy. This
      revision offers us the opportunity to discuss this complex case, comparing
      different points of view, and to present the results of the molecular analyses
      carried out on Carlo's bone samples. We looked for the genetic risk factors of
      rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We also searched for the
      primary candidate genes of RA and PsA, i.e. DR4 or DR1 and Cw6 or DR7
      respectively, the latter predisposing also for psoriasis. METHODS: An original
      molecular protocol was applied to achieve an aDNA uncontaminated by exogenous
      sources and almost intact, starting from one of the Cardinal's rib pieces. The
      allele risk factors for both diseases were identified by PCR-SSP assay as HLA
      genotyping methodology. RESULTS: Our data assigned Carlo the genotype DRB1*04/*11
      for HLA-DRB locus and Cw*04/*12 for HLA-C locus. CONCLUSIONS: Since Carlo was
      infected by M. tuberculosis during infancy and was carrying the DR4 variant but
      not the Cw6, he surely had a predisposition to RA, not to PsA and/or psoriasis.
      The diagnosis of RA is thus confirmed.

PMID- 22152117
TI  - Gene-temperament interactions might distinguish between bipolar I and bipolar II
      disorders: a cross-sectional survey of Han Chinese in Taiwan.
AB  - BACKGROUND: Whether bipolar II disorder is a distinct disorder or simply a milder
      form of bipolar I disorder has been debated. Family, twin, and adoption studies
      provide robust evidence of genetic contributions to bipolar disorder, and
      heritable temperaments are also believed to contribute to the susceptibility to
      bipolar disorders. In this study, we sought to clarify the relationship between
      bipolar I and bipolar II disorder. METHOD: In this cross-sectional survey, 314
      participants (82 bipolar I disorder patients, 121 bipolar II disorder patients,
      and 111 healthy controls) completed the Hamilton Depression Rating Scale, the
      Young Mania Rating Scale, and the Tridimensional Personality Questionnaire, which
      assessed the personality dimensions of novelty seeking and harm avoidance. We
      also determined which participants carried the serine-to-glycine substitution at
      amino acid position 9 polymorphism of the dopamine D3 receptor gene (DRD3) and
      the serotonin transporter gene-linked polymorphic region (5-HTTLPR) genotypes.
      All patients met the DSM-IV-TR diagnosis criteria for bipolar disorder. This
      study was conducted from September 2005 to July 2009 at National Cheng Kung
      University Hospital, Tainan, Taiwan, and Tri-Service General Hospital, Taipei,
      Taiwan. RESULTS: Binary logistic regression analysis showed significant main
      effects for the 5-HTTLPR polymorphism (P = .045), novelty seeking (P = .022), and
      harm avoidance (P = .017) scores and a significant interaction effect between
      harm avoidance and 5-HTTLPR genotypes (P = .042) in distinguishing between
      bipolar I and bipolar II disorder patients. Bipolar I disorder patients with the
      long allele at 5-HTTLPR had lower harm avoidance scores than did bipolar II
      disorder patients (bipolar I disorder = 16.23, bipolar II disorder = 19.80; P =
      .023); however, the difference was not significant after multiple test
      correction. All these data suggest a distinction between bipolar I and bipolar II
      disorder. CONCLUSIONS: We provide initial evidence that 5-HTTLPR genotypes might
      moderate the association between harm avoidance and bipolar I and bipolar II
      disorder. There appear to be unique differences in the gene-temperament
      interactions of bipolar I and bipolar II disorder patients.

PMID- 22152118
TI  - Metabolism of amyloid-beta protein may be affected in depression.
AB  - OBJECTIVE: Epidemiologic studies have demonstrated that a history of depression
      increases the risk of developing Alzheimer's disease, particularly among
      individuals with early-onset depression. On the other hand, recent studies have
      suggested that a higher amyloid-beta protein (Abeta)40 to Abeta42 ratio may be
      associated with the future onset of Alzheimer's disease. Our objective was to
      assess whether the pathophysiology of early-onset depression may involve or
      affect Abeta metabolism. METHOD: In this extension of a case-control pilot study,
      193 inpatients with DSM-IV major depressive disorder (MDD) (mean age = 55.9
      years) from the Juntendo Koshigaya Hospital, Saitama, Japan, and 413 healthy
      controls from the community (mean age = 56.6 years) were recruited between May
      2004 and April 2009. Serum Abeta40 and Abeta42 levels, Abeta40/Abeta42 ratio, and
      other clinical and biological factors were compared between controls and patients
      in 3 age groups: young (< 40 years), middle-aged (>= 40 to < 65 years), and
      elderly (>= 65 years). Depressive symptoms were assessed with the Hamilton
      Depression Rating Scale. All patients were receiving antidepressant medication at
      the time of the study, and doses of current antidepressants were converted to an
      equivalent imipramine dose. RESULTS: The serum Abeta40/Abeta42 ratio was
      significantly higher in MDD patients than controls in all age groups (young: P =
      .003; middle-aged: P < .001; elderly: P = .006). These differences were also
      observed in noncarriers of the apolipoprotein E epsilon4 allele. CONCLUSIONS: Our
      findings suggest that Abeta metabolism may be affected in depression; these
      findings also possibly answer the question of why even early-onset depression is
      a risk factor for developing Alzheimer's disease.

PMID- 22152119
TI  - Docking studies on novel analogues of 8 methoxy fluoroquinolones against GyrA
      mutants of Mycobacterium tuberculosis.
AB  - BACKGROUND: Fluoroquinolone resistance is a serious threat in the battle against
      the treatment of multi drug resistant tuberculosis (MDR-TB) and extensively drug
      resistant tuberculosis (XDR-TB). Fluoroquinolone resistant isolates from India
      had shown to have evolved several mutants in the quinolone resistance determining
      region (QRDR) of DNA gyrase A subunit (GyrA), the target of fluoroquinolone. In
      view of high prevalence of mutations in the 'hot spot' region, a study on
      combinatorial drug design was carried out to identify better analogues for the
      treatment of MDR-TB. The gyrA subunit 'hot spot' region of codons 90, 94 and 95
      were modeled into their corresponding protein folds and used as receptors for the
      docking studies. Further, invitro tests were carried using the parent compounds,
      namely gatifloxacin and moxifloxacin and correlated with the obtained docking
      scores. RESULTS: Molecular docking and in vitro studies correlated well in
      demonstrating the enhanced activity of moxifloxacin, when compared to
      gatifloxacin, on ofloxacin sensitive and resistant strains comprising of clinical
      isolates of MDR-TB. The evolved lead structures targeting against mutant QRDR
      receptors were guanosine and cholesteryl esters of gatifloxacin and moxifloxacin.
      They showed consistently high binding affinity values of -10.3 and -10.1 kcal/mol
      respectively with the target receptors. Of these, the guanosine ester showed
      highest binding affinity score and its log P value lied within the Lipinski's
      range indicating that it could have better absorptivity when it is orally
      administered thereby having an enhanced activity against MTB. CONCLUSIONS: The
      docking results showed that the addition of the cholesteryl and guanosine esters
      to the 'DNA gyrase binding' region of gatifloxacin and moxifloxacin enhanced the
      binding affinity of these parent molecules with the mutant DNA gyrase receptors.
      Viewing the positive correlation for the docking and in vitro results with the
      parent compounds, these lead structures could be further evaluated for their in
      vitro and in vivo activity against MDR-TB.

PMID- 22152121
TI  - Motivational interviewing and interaction skills training for parents to change
      cannabis use in young adults with recent-onset schizophrenia: a randomized
      controlled trial.
AB  - BACKGROUND: Cannabis use by people with schizophrenia has been found to be
      associated with family distress and poor clinical outcomes. Interventions to
      reduce drug use in this patient group have had limited efficacy. This study
      evaluated the effectiveness of a novel intervention for parents of young adults
      with recent-onset schizophrenia consisting of family-based motivational
      interviewing and interaction skills (Family Motivational Intervention, FMI) in
      comparison with routine family support (RFS). METHOD: In a trial with 75 patients
      who used cannabis and received treatment for recent-onset schizophrenia, 97
      parents were randomly assigned to either FMI (n=53) or RFS (n=44). Assessments
      were conducted at baseline and 3 months after completion of the family
      intervention by an investigator who remained blind throughout the study about the
      assignment of the parents. RESULTS: At follow-up, patients' frequency and
      quantity of cannabis use was significantly more reduced in FMI than in RFS
      (p<0.05 and p<0.04 respectively). Patients' craving for cannabis was also
      significantly reduced in FMI whereas there was a small increase in RFS (p=0.01).
      There was no difference between FMI and RFS with regard to patients' other
      substance use and general level of functioning. Both groups showed significant
      improvements in parental distress and sense of burden. CONCLUSIONS: Training
      parents in motivational interviewing and interaction skills is feasible and
      effective in reducing cannabis use among young adults with recent-onset
      schizophrenia. However, FMI was not more effective than RFS in increasing
      patients' general level of functioning and in reducing parents' stress and sense
      of burden.

PMID- 22152120
TI  - A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection
      and radiotherapy in high-risk soft tissue sarcoma.
AB  - BACKGROUND: The role of chemotherapy in high-risk soft tissue sarcoma is
      controversial. Though many patients undergo initial curative resection, distant
      metastasis is a frequent event, resulting in 5-year overall survival rates of
      only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to
      achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate
      occult metastasis. Here we report on the results of our non-randomized phase II
      study on neo-adjuvant treatment for high-risk STS. METHOD: Patients with
      potentially curative high-risk STS (size >= 5 cm, deep/extracompartimental
      localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised
      4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m(2) iv days 1 and
      4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m(2) day 1,
      pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative
      radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. RESULT: Between
      06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age
      50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of
      primary tumors were located in the extremities or trunk (92%), 6% originated in
      the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was
      6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local
      recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12
      patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years
      was 83% and 68%, respectively. Multivariate analysis failed to prove influence of
      resection status or grade of histological necrosis on OS or DFS. Severe
      toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS
      toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of
      secondary leukemias were observed so far. CONCLUSION: The current protocol is
      feasible for achieving local control rates, as well as OS and DFS comparable to
      previously published data on neo-/adjuvant chemotherapy in this setting. However,
      the definitive role of chemotherapy remains unclear in the absence of large,
      randomized trials. Therefore, the current regimen can only be recommended within
      a clinical study, and a possibly increased risk of secondary leukemias has to be
      taken into account. TRIAL REGISTRATION: ClinicalTrials.gov NCT01382030, EudraCT
      2004-002501-72.

PMID- 22152122
TI  - Including emergency and acute care as a global health priority.
AB  - A recent important global meeting to set the international action agenda
      concerning non-communicable diseases (NCDs) failed to draw substantial attention
      from the emergency medical and surgical community. Advocacy efforts on the part
      of emergency clinicians should be increased to highlight the critical services we
      provide and create an approach to addressing NCDs with the most effective balance
      of preventive and acute care services. Acute care, which encompasses all
      frontline treatment services for sudden or unexpected injury or illness, can
      serve as a focal point for the development of the common language and body of
      research needed to draw the attention of global leaders and policy makers.

PMID- 22152123
TI  - Fast and accurate methods for phylogenomic analyses.
AB  - BACKGROUND: Species phylogenies are not estimated directly, but rather through
      phylogenetic analyses of different gene datasets. However, true gene trees can
      differ from the true species tree (and hence from one another) due to biological
      processes such as horizontal gene transfer, incomplete lineage sorting, and gene
      duplication and loss, so that no single gene tree is a reliable estimate of the
      species tree. Several methods have been developed to estimate species trees from
      estimated gene trees, differing according to the specific algorithmic technique
      used and the biological model used to explain differences between species and
      gene trees. Relatively little is known about the relative performance of these
      methods. RESULTS: We report on a study evaluating several different methods for
      estimating species trees from sequence datasets, simulating sequence evolution
      under a complex model including indels (insertions and deletions), substitutions,
      and incomplete lineage sorting. The most important finding of our study is that
      some fast and simple methods are nearly as accurate as the most accurate methods,
      which employ sophisticated statistical methods and are computationally quite
      intensive. We also observe that methods that explicitly consider errors in the
      estimated gene trees produce more accurate trees than methods that assume the
      estimated gene trees are correct. CONCLUSIONS: Our study shows that highly
      accurate estimations of species trees are achievable, even when gene trees differ
      from each other and from the species tree, and that these estimations can be
      obtained using fairly simple and computationally tractable methods.

PMID- 22152124
TI  - Health state utilities of a population of Nigerian hypertensive patients.
AB  - BACKGROUND: Establishment of the health impact of hypertension on quality of life
      of Nigerians is a step towards controlling the disease. The study aimed to
      provide a Nigerian specific reference list of utility scores of hypertensive
      patients with various interacting conditions. FINDINGS: An interviewer-based,
      cross-sectional study was conducted using hypertensive patients in two
      purposively selected tertiary hospitals located in South-Eastern Nigeria. Health
      Utility Index Mark 3 (HUI3) was used.A total of 384 participants with either
      hypertension alone or with hypertension-associated complications were interviewed
      in the two tertiary hospitals.The overall mean utility score was 0.35 +/- 0.42.
      Patients with hypertension alone had the highest overall mean utility score (0.57
      +/- 0.29) while hypertensive patients with stroke had the lowest overall mean
      score (0.04 +/- 0.36). Being a male, increase in age and mean arterial blood
      pressure, emergency visit and loss of work due to illness were associated with
      significant decrease in overall utility scores. CONCLUSIONS: This study presented
      a reference for health state utilities of a population of Nigerian hypertensive
      patients.

PMID- 22152126
TI  - Does dalteparin PROTECT better than heparin?

PMID- 22152125
TI  - Development and validation of the impact of dry eye on everyday life (IDEEL)
      questionnaire, a patient-reported outcomes (PRO) measure for the assessment of
      the burden of dry eye on patients.
AB  - OBJECTIVE: To develop and validate a comprehensive patient-reported outcomes
      instrument focusing on the impact of dry eye on everyday life (IDEEL). METHODS:
      Development and validation of the IDEEL occurred in four phases: 1) focus groups
      with 45 dry eye patients to develop a draft instrument, 2) item generation, 3)
      pilot study to assess content validity in 16 patients and 4) psychometric
      validation in 210 subjects: 130 with non-Sjogren's keratoconjunctivitis sicca, 32
      with Sjogren's syndrome and 48 controls, and subsequent item reduction. RESULTS:
      Focus groups identified symptoms and the associated bother, the impact of dry eye
      on daily life and the patients' satisfaction with their treatment as the central
      concepts in patients' experience of dry eye. Qualitative analysis indicated that
      saturation was achieved for these concepts and yielded an initial 112-item draft
      instrument. Patients understood the questionnaire and found the items to be
      relevant indicating content validity. Patient input, item descriptive statistics
      and factor analysis identified 55 items that could be deleted. The final 57-item
      IDEEL assesses dry eye impact constituting 3 modules: dry eye symptom-bother, dry
      eye impact on daily life comprising impact on daily activities, emotional impact,
      impact on work, and dry eye treatment satisfaction comprising satisfaction with
      treatment effectiveness and treatment-related bother/inconvenience. The
      psychometric analysis results indicated that the IDEEL met the criteria for item
      discriminant validity, internal consistency reliability, test-retest reliability
      and floor/ceiling effects. As expected, the correlations between IDEEL and the
      Dry Eye Questionnaire (a habitual symptom questionnaire) were higher than between
      IDEEL and Short-Form-36 and EuroQoL-5D, indicating concurrent validity.
      CONCLUSION: The IDEEL is a reliable, valid and comprehensive questionnaire
      relevant to issues that are specific to dry eye patients, and meets current FDA
      patient-reported outcomes guidelines. The use of this questionnaire will provide
      assessment of the impact of dry eye on patient dry eye-related quality of life,
      impact of treatment on patient outcomes in clinical trials, and may aid in
      treatment effectiveness evaluation.

PMID- 22152127
TI  - Psychometrics of the Montreal Cognitive Assessment (MoCA) and its subscales:
      validation of the Taiwanese version of the MoCA and an item response theory
      analysis.
AB  - BACKGROUND: The Montreal Cognitive Assessment (MoCA) is an instrument for
      screening mild cognitive impairment (MCI). This study examined the psychometric
      properties and the validity of the Taiwan version of the MoCA (MoCA-T) in an
      elderly outpatient population. METHODS: Participants completed the MoCA-T, Mini
      Mental State Examination (MMSE), and the Chinese Version Verbal Learning Test.
      The diagnosis of Alzheimer's disease (AD) was made based on the NINCDS-ADRDA
      criteria, and MCI was diagnosed through the criteria proposed by Petersen et al.
      (2001). RESULTS: Data were collected from 207 participants (115 males/92 females,
      mean age: 77.3 +/- 7.5 years). Ninety-eight participants were diagnosed with AD,
      71 with MCI, and 38 were normal controls. The area under the receiver operator
      curves (AUC) for predicting AD was 0.98 (95% confidence interval [CI] = 0.97
      1.00) for the MMSE, and 0.99 (95% CI = 0.98-1.00) for the MoCA-T. The AUC for
      predicting MCI was 0.81 (95% CI = 0.72-0.89) using the MMSE and 0.91 (95% CI =
      0.86-1.00) using the MoCA-T. Using an optimal cut-off score of 23/24, the MoCA-T
      had a sensitivity of 92% and specificity of 78% for MCI. Item response theory
      analysis indicated that the level of information provided by each subtest of the
      MoCA-T was consistent. The frontal and language subscales provided higher
      discriminating power than the other subscales in the detection of MCI.
      CONCLUSION: Compared to the MMSE, the MoCA-T provides better psychometric
      properties in the detection of MCI. The utility of the MoCA-T is optimal in mild
      to moderate cognitive dysfunction.

PMID- 22152128
TI  - Expectant management of pneumothorax in preterm infants receiving assisted
      ventilation: report of 4 cases and review of the literature.
AB  - Pneumothorax is a common complication in infants receiving assisted ventilation.
      The appropriate management of this condition is not always clearly defined,
      especially when a large air leak and mediastinal shift are present but the infant
      is hemodynamically stable. Despite the complications  associated with chest tube
      placement, this remains the most common approach in such cases. We report 4 cases
      of preterm infants who developed large pneumothoraces with mediastinal shift
      while on assisted ventilation and were managed conservatively, with substantial
      improvement within 12-96  hours. In this report we also review the literature on
      pneumothorax in preterm infants.

PMID- 22152129
TI  - Synthesis and properties of acetamidinium salts.
AB  - BACKGROUND: Acetamidines are starting materials for synthesizing many chemical
      substances, such as imidazoles, pyrimidines and triazines, which are further used
      for biochemically active compounds as well as energetic materials. The aim of
      this study was to synthesise and characterise a range of acetamidinium salts in
      order to overcome the inconvenience connected with acetamidinium chloride, which
      is the only commercially available acetamidinium salt. RESULTS: Acetamidinium
      salts were synthesised and characterised by elemental analysis, mass
      spectrometry, NMR and - in the case of energetic salts - DTA. The structures of
      previously unknown acetamidinium salts were established by X-ray diffraction
      analysis. Hygroscopicities in 90% humidity of eight acetamidinium salts were
      evaluated. CONCLUSIONS: The different values of hygroscopicity are corroborated
      by the structures determined by X-ray analysis. The acetamidinium salts with 2D
      layered structures (acetamidinium nitrate, formate, oxalate and dinitromethanide)
      show a lack of hygroscopicity, and the compounds with 3D type of structure
      (acetamidinium chloride, acetate, sulphate and perchlorate) and possessing rather
      large cavities are quite hygroscopic.

PMID- 22152130
TI  - Impact of social mobility and geographical migration on variation in male height,
      weight and body mass index in a British cohort.
AB  - Using a sample of 2090 British father and son pairs the relationships between
      social and geographical intra- and inter-generational mobility were examined in
      relation to height, weight and body mass index (BMI). There was much more social
      mobility than geographical (regional) migration. Social mobility and geographical
      migration were not independent: socially non-mobile fathers and sons were more
      likely to be geographical non-migrants, and upwardly socially mobile fathers and
      sons were more likely to be regional migrants. Upwardly socially mobile fathers
      and sons were, on average, taller and had a lower BMI than non-mobile and
      downwardly mobile fathers and sons. In general, no significant associations were
      found between geographical migration and height or weight. Migrating fathers had
      a lower BMI than sedentes, as did their sons who migrated between 1965 and 1991.
      There was no significant interaction that indicated that social mobility and
      geographical migration were acting in a simple additive way on height, weight and
      BMI.

PMID- 22152131
TI  - Biomarkers of acute lung injury: worth their salt?
AB  - The validation of biomarkers has become a key goal of translational biomedical
      research. The purpose of this article is to discuss the role of biomarkers in the
      management of acute lung injury (ALI) and related research. Biomarkers should be
      sensitive and specific indicators of clinically important processes and should
      change in a relevant timeframe to affect recruitment to trials or clinical
      management. We do not believe that they necessarily need to reflect pathogenic
      processes. We critically examined current strategies used to identify biomarkers
      and which, owing to expedience, have been dominated by reanalysis of blood
      derived markers from large multicenter Phase 3 studies. Combining new and
      existing validated biomarkers with physiological and other data may add
      predictive power and facilitate the development of important aids to research and
      therapy.

PMID- 22152132
TI  - ATP synthase ecto-alpha-subunit: a novel therapeutic target for breast cancer.
AB  - BACKGROUND: Treatment failure for breast cancer is frequently due to lymph node
      metastasis and invasion to neighboring organs. The aim of the present study was
      to investigate invasion- and metastasis-related genes in breast cancer cells in
      vitro and in vivo. Identification of new targets will facilitate the
      developmental pace of new techniques in screening and early diagnosis. Improved
      abilities to predict progression and metastasis, therapeutic response and
      toxicity will help to increase survival of breast cancer patients. METHODS:
      Differential protein expression in two breast cancer cell lines, one with high
      and the other with low metastatic potential, was analyzed using two-dimensional
      liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed
      by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI
      TOF/MS). RESULTS: Up regulation of alpha-subunit of ATP synthase was identified
      in high metastatic cells compared with low metastatic cells. Immunohistochemical
      analysis of 168 human breast cancer specimens on tissue microarrays revealed a
      high frequency of ATP synthase alpha-subunit expression in breast cancer (94.6%)
      compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels
      of ATP synthase expression levels strongly correlated with large tumor size, poor
      tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase alpha
      subunit over-expression was detected on the surface of a highly invasive breast
      cancer cell line. An antibody against the ATP synthase alpha-subunit inhibited
      proliferation, migration and invasion in these breast cancer cells but not that
      of a non-tumor derived breast cell line. CONCLUSIONS: Over-expression of ATP
      synthase alpha-subunit may be involved in the progression and metastasis of
      breast cancer, perhaps representing a potential biomarker for diagnosis,
      prognosis and a therapeutic target for breast cancer. This finding of this study
      will help us to better understand the molecular mechanism of tumor metastasis and
      to improve the screening, diagnosis, as well as prognosis and/or prediction of
      responses to therapy for breast cancer.

PMID- 22152133
TI  - Novel insights into maintaining genomic integrity: Wee1 regulating Mus81/Eme1.
AB  - Maintenance of genomic integrity is essential for cell survival. Specifically,
      during DNA replication cells use a complex network of mechanisms that prevents
      genomic instability. Recently, we and others identified Wee1, a serine/threonine
      and tyrosine kinase, as a new modulator of the genomic stability during S phase.
      Loss of its activity causes a general DNA damage response activation and a
      decrease in replication fork speed. These effects are counteracted by the
      downregulation of the endonuclease complex Mus81-Eme1, showing a new link between
      this endonuclease and Wee1 during DNA replication. Here we discuss the function
      of Wee1 in genomic stability and its relationship with the Mus81-Eme1 complex.

PMID- 22152134
TI  - Postoperative mortality and morbidity in octogenarians and nonagenarians with hip
      fracture: an analysis of perioperative risk factors.
AB  - OBJECTIVE: To evaluate the role of high risk factors in octogenarians and
      nonagenarians with hip trauma, which may lead to excessive mortality and morbi-
      dity postoperatively. METHODS: Fifty-four octogenarians and nonagenarians
      patients were enrolled in the study, receiving surgical repair of hip fracture in
      our hospital from January 2006 to January 2010. High risk factors were recorded
      preoperatively in detail. Complications and survival state were followed up by
      telephone for 2 years postoperatively. All the data were analyzed by Chi-square
      test with SPSS 13.0. RESULTS: Twenty-six males (48.1%), aged from 80 to 94 years
      with a mean age of 84.2 years, and twenty-eight females (51.9%), aged from 80 to
      95 years with a mean age of 83.4 years, were presented in the cohort study. The
      hip traumas were caused by daily slight injuries (52 cases) and car accidents (2
      cases), respectively. Twenty-eight patients (51.9%) with femoral neck fracture
      while 26 patients (48.1%) with intertrochanteric fracture were diagnosed through
      an anterior-posterior pelvic radiophotograph. In this series, 39 patients (72.2%)
      suffered from one or more comorbidities preoperatively. The morbidity was 48.1%
      and the major cause was urinary tract infection, while a significant difference
      was noted between females and males. The mortality was 20.4% with a predominant
      cause of acute renal failure. CONCLUSIONS: The gender should be considered as a
      critical high risk factor in octogenarians and nonagenarians with hip trauma
      postoperatively. Females are more likely to suffer complications postoperatively,
      which is especially obvious in senile patients over 80 years (P less than 0.05).
      Urinary tract infection is the most frequent complication after hip surgery,
      followed by low limb embolism and malnutrition. The mortality is dramatically
      greater in patients over 80 years old than those below, and major causes are
      acute renal failure, multiple organ dysfunction syndrome and mental
      deterioration. Multidisciplinary consultations and mental assessment are
      encouraged in patients over 80 years old after hip trauma and surgery. Hip
      fractures in octogenarians and nonagenarians deserve special attention because of
      their advanced age and comorbidities.

PMID- 22152135
TI  - Adipose-derived stromal vascular fraction improves tendon healing in rabbits.
AB  - OBJECTIVE: To evaluate the potential effects of uncultured adipose-derived
      stromal vascular fraction on tendon healing. METHODS: Twenty five adult male New
      Zealand white rabbits weighing 2.5-3.0 kg were used. Five rabbits were used as
      donors of adipose tissue and the rest were divided into control and treatment
      groups. The injury model was completed by unilateral tenotomy through the middle
      one third of deep digital flexor tendon. Immediately after suture repair, either
      fresh stromal vascular fraction from enzymatic digestion of adipose tissue or
      placebo was intratendinously injected at tendon stumps in treatment and control
      groups, respectively. Immobilization with cast was continued for two weeks after
      surgery. Animals were sacrificed at eight weeks after surgery and tendons
      underwent histological, immunohistochemical, and mechanical evaluations.
      Statistical analyses of quantitative and qualitative data were assessed using one
      way analysis of variance and Mann-Whitney U-test, respectively. RESULTS:
      Histological evaluations demonstrated superior fibrillar linearity and
      continuity, and decreased vascularity in treatment group indicated improved
      organization and remodeling of neotendons. Immunohistochemistry de- monstrated a
      significant increase in collagen I expression in treatment group. Ultimate load
      and energy absorption capacity were both significantly increased in cell-treated
      repairs compared with controls. CONCLUSION: The present study shows that
      intratendinous injection of uncultured adipose-derived stromal vascular fraction
      results in improved structural and mechanical properties of tendon repairs and it
      could be an effective modality for treating tendon injury.

PMID- 22152136
TI  - Fall of platelet count in children with traumatic brain injury: is it of value?
AB  - OBJECTIVE: Trauma is the leading cause of mortality and morbidity among young age
      groups in Saudi Arabia and developed countries. This study aimed to evaluate the
      fall of platelet count in children with traumatic brain injury (TBI) as a
      potential predictor for clinical severity and outcome. METHODS: Totally 74
      patients with TBI were admitted to the Pediatric Intensive Care Unit (PICU) of
      our hospital from the beginning of January 2008 to the end of March 2010 (27
      months). Baseline enrolling criteria were age less than or equal to 12 years,
      admission within 4 hours after trauma event, and abbreviated injury scale (AIS)
      less than 3 for extracranial injuries. Injury severity was classified as mild,
      moderate and severe according to their Glasgow Coma Scale (GCS) scores. Clinical
      outcomes at discharge were defined as poor (death, severe neurological morbidity)
      and favorable (moderate disability and good recovery). Platelet count was taken 2
      3 times on the first day after admission and thereafter once daily. The
      percentage fall of platelet count (PFP) was calculated and taken as an index of
      change. PFP was considered zero if the platelet count was higher than the initial
      value. RESULTS: PFP was significantly higher in patients with poor outcomes (mean
      56.0%+/-3.8%, median 55.5%) compared to those with favorable outcomes (mean
      25.3%+/-3.2%, median 20.5%, P less than 0.01). PFP was also closely related to
      the severity of TBI, GCS score, clinical outcome and length of stay for survivors
      (P less than 0.01 for each). The frequency of thrombocytopenia was significantly
      higher in poor outcome patients than in favorable outcome patients (P less than
      0.05). The validity of thrombocytopenia as a risk factor to predict poor outcome
      after TBI was: specificity, 77.4%; odd ratio (OR), 3.1; relative risk (RR), 2.15.
      Receiver operating characteristic (ROC) curve and Youden index showed that the
      optimum cutoff point of PFP was at 51.5%. CONCLUSION: PFP is increased with the
      severity of TBI and it can be taken as a significant independent predicting
      factor for its outcome as well.

PMID- 22152137
TI  - Posttraumatic hydrocephalus associated with decompressive cranial defect in
      severe brain-injured patients.
AB  - OBJECTIVE: To investigate the occurrence of posttraumatic hydrocephalus (PTH) in
      severe brain- injured patients who underwent decompressive craniectomy (DC) and
      to discuss the management. METHODS: A total of 389 patients suffering from severe
      head trauma between January 2004 and May 2010 were enrolled in this study.
      Clinical data were analyzed retrospectively. Of them, 149 patients who underwent
      DC were divided into two groups according to the presence of PTH: hydrocephalus
      group and nonhydrocephalus group. Clinical factors including preoperative Glasgow
      Coma Score (GCS), bilateral or unilateral decompression, and duraplasty in DC
      were assessed by single factor analysis to determine its relationship with the
      occurrence of PTH. RESULTS: Of the 149 patients undergoing DC, 25 (16.8%)
      developed PTH; while 23 developed PTH (9.6%) among the rest 240 patients without
      DC. Preoperative GCS, bilateral or unilateral decompression, duraplasty in DC
      were significantly associated with the development of PTH. Ventriculoperitoneal
      shunt was performed on 23 of 25 patients with PTH after DC. Frontal horn was
      preferred for the placement of the catheter. Sixteen of them were operated upon
      via frontal approach and 7 via occipital approach. After shunt surgery, both
      radiological and clinical improvements were confirmed in 19 patients.
      Radiological improvement was found in 2 patients. One patient died eventually of
      severe pneumonia. Shunt-related infection occurred in 1 patient, which led to the
      removal of the catheter. CONCLUSIONS: It is demonstrated that the occurrence of
      PTH is high in patients with large decompressive skull defect. Patients with low
      GCS and bilateral decompression tend to develop PTH after DC. Duraplasty in DC
      might facilitate reducing the occurrence of PTH. Patients with PTH concomitant
      skull defect should be managed deliberately to restore the anatomical and
      physiological integrity so as to facilitate the neurological resuscitation.

PMID- 22152138
TI  - Strengthening injury surveillance system in iran.
AB  - OBJECTIVE: To strengthen the current Injury Surveillance System (IS System) in
      order to better monitor injury conditions, improve protection ways and promote
      safety. METHODS: At first we carried out a study to evaluate the frameworks of IS
      System in the developed countries. Then all the available documents from World
      Health Organization, Eastern Mediterranean Regional Organization, as well as
      Minister of Health and Medical Education concerning Iran were reviewed. Later a
      national stakeholder's consultation was held to collect opinions and views. A
      national workshop was also intended for provincial representatives from 41
      universities to identify the barriers and limitations of the existing program and
      further to strengthen injury surveillance. RESULTS: The evaluation of the current
      IS System revealed many problems, mainly presented as lack of accurate pre- and
      post-hospital death registry, need of precise injury data registry in outpatient
      medical centers, incomplete injury data registry in hospitals and lack of
      accuracy in definition of variables in injury registry. The five main
      characteristics of current IS System including flexibility, acceptability,
      simplicity, usefulness and timeliness were evaluated as moderate by experts.
      CONCLUSIONS: Major revisions must be considered in the current IS System in Iran.
      The following elements should be added to the questionnaire: identifier, manner
      of arrival to the hospital, situation of the injured patient, consumption of
      alcohol and opioids, other involved participants in the accident, intention,
      severity and site of injury, side effects of surgery and medication, as well as
      one month follow-up results. Data should be collected from 10% of all hospitals
      in Iran and analyzed every 3 months. Simultaneously data should be online to be
      retrieved by researches.

PMID- 22152139
TI  - Dynamic activity of NF-kappaB in multiple trauma patients and protective effects
      of ulinastain.
AB  - OBJECTIVE: To investigate the dynamic activity of NF-kappaB  at the early stage
      of injury in multiple trauma patients and the protective effects of ulinastain.
      METHODS: From January 2008 to May 2010,  patients with multiple traumas admitted
      to our emergency department were enrolled in this study. Their age varied from 20
      55 years. All enrolled patients were assigned randomly into control group (26
      cases of multiple injury without ulinastain treatment), ulinastain group (25
      cases of multiple injury with ulinastain treatment), and mild injury group (20
      cases) for basic control. The inclusion criteria for mild injury group were AIS
      2005 less than or equal to 3, single wound, previously healthy inhospital
      patients without the history of surgical intervention. In addition to routine
      treatment, patients in ulinastain group were intravenously injected 200 000 IU of
      ulinastain dissolved in 100 ml of normal saline within 12 hours after injury and
      subsequently injected at the interval of every 8 hours for 7 days. NF-kappaB 
      activity in monocytes and the level of TNF-alpha,IL-1, IL-6 in serum on admission
      (day 0), day 1, 2, 3, 4, and 7  were measured. Data were compared and analyzed
      between different groups. RESULTS: NF-kappaB  activity in monocytes and TNF
      alpha,IL-1 and IL-6 of these patients reached peak levels at 24 hour after
      trauma, with gradual decrease to normal at 72 hour after trauma. NF-kappaB 
      activity and levels of TNF-alpha,IL-1 and IL-6 were lower in ulinastain group
      than control one, without any significant difference between the two groups. The
      mean duration for systemic inflammatory response syndrome and multiple organ
      dysfunction syndrome was 7 d+/-3.1 d and  10 d+/-3.5 d in ulinastain group and
      control group respectively, and showed a significant difference. CONCLUSIONS: NF
      kappaB  activity in monocytes and the levels of inflammatory cytokines in 
      multiply injured patients increased transiently at the early stage of trauma.
      Ulinastain may shorten the duration of systemic inflammatory response syndrome
      and multiple organ dysfunction syndrome, but does not show the ability to
      decrease the activity of NF-kappaB .

PMID- 22152140
TI  - Epidemiology of eye injuries sustained by military personnel in China.
AB  - OBJECTIVE: To investigate the epidemiological characteristics of eye injuries
      sustained by military personnel in Chinese army. METHODS: Eleven military
      evacuation hospitals located in different regions were selected for this study.
      We reviewed all the medical records of eye injuries sustained by military
      personnel between January 2005 and December 2009. Patients'information was
      collected. All data were put into database and analyzed statistically. RESULTS:
      Totally there were 415 inpatients with eye injuries (442 eyes) and their mean age
      was 24.40 years. Eye injury accounts for 13.51% of all eye diseases in this
      study. From 2006 to 2009, the number of eye injury increased gradually. Among
      them, 175 (42.17%) were injured in leisure time, and 145 (34.94%) in working
      time. Twenty-two (5.30%) patients had an eye surgery or history of eye disease
      before injury. In all, 246 patients (59.28%) were sent to evacuation hospital
      within 24 hours and 64 (56.64%) underwent surgeries in 24 hours after injury.
      There were 389 patients (93.73%) hospitalized for 1 time. Visual acuities of 187
      eyes (42.31%)  were grade 1 (larger than or equal to 20/40) after injury. When
      discharge, 349 eyes (78.96%) obtained a visual acuity of grade 1. CONCLUSION: Eye
      injury has a very frequent incidence in Chinese army and much more attention
      should be paid to prevent it.

PMID- 22152141
TI  - Emergency management of hemodynamically unstable pelvic fractures.
AB  - Pelvic fractures are serious injuries. Death within 24 hours is most often a
      result of acute blood loss. The emergency management of these patients is
      challenging and controversial. The key issues in its management are identifying
      the site(s) of hemorrhage and then controlling the bleeding. Management of
      hemodynamically unstable patients with pelvic fracture requires a multidisci-
      plinary team. The issues addressed in this management algorithm are diagnostic
      evaluation, damage control resuscitation, indications for noninvasive pelvic
      stabilization, preperitoneal pelvic packing and the critical decisions concerning
      surgical options and angiography. This review article focuses on the recent body
      of know- ledge on those determinations.

PMID- 22152142
TI  - Irreducible traumatic posterior hip dislocation with entrapment and a buttonhole
      effect.
AB  - The authors reported the case of a 27-year-old man who sustained an irreducible
      postero-lateral traumatic dislocation of the hip with capsular and labral
      entrapment. Initial X-rays showed only a small acetabular fragment. After two
      attempts to reduce the hip with muscle paralysis under general anaesthesia
      failed, the patient was treated by immediate open reduction through a postero
      lateral approach. Surgical exploration of the hip revealed a small osteochondral
      fragment attached to a large piece of labrum and capsule, clogging the
      acetabulum. The femoral head crossed over the torn capsule with a buttonhole
      effect. These elements were relieved, the bone fragment was fixed with a 2 mm
      screw and the capsule was repaired. At the 10-year follow-up, the functional
      outcome was excellent with a Harris score of 100 points and no signs of necrosis
      or osteoarthritis. The authors propose a literature review of this uncommon
      lesion.

PMID- 22152143
TI  - Internal fixation and bone grafting for intraarticular nonunion of tibial
      plateau: a report of four cases.
AB  - Intraarticular nonunion of tibial plateau is rare. In the literature, only 9
      patients were found to be treated for intraarticular tibial plateau nonunion and
      they got varying results. Internal fixation along with bone grafting was done as
      a standard treatment in all cases. We treated 4 different profile cases of
      intraarticular tibial plateau nonunion in our institution by 4 different methods.
      We treated these cases with plaster of paris cast, internal fixation along with
      bone graft, arthrodesis with K-nail and total knee replacement. Case 1 was
      treated with plaster of paris (POP) cast as the patient refused surgery. The
      fracture was united and the patient was fully satisfied with full range of motion
      despite valgus malalignment. Case 2 was managed with open reduction internal
      fixation along with bone grafting. The patient had a good union and got full
      range of motion at the knee joint. Case 3 was treated with total knee
      arthroplasty due to her old age and got satisfactory result. Case 4 was an
      infected nonunion. Arthrodesis was done and the patient could walk with full
      weight bearing independently. We conclude that internal fixation along with bone
      grafting may not be suitable in all cases of intraarticular nonunion of tibial
      plateau. Causes of nonunion, present condition and range of motion of the knee
      joint, as well as the age of patient should be all considered and the treatment
      should be individualised according to each patient's situation.

PMID- 22152144
TI  - Hoffa fracture associated with ipsilateral femoral shaft fracture: clinical
      feature and treatment.
AB  - Hoffa fracture associated with ipsilateral femoral shaft fracture is very rare.
      Three cases of this rare type of injury were retrospectively reviewed. The sites
      of femoral shaft fractures and Hoffa fractures were documented. All femoral shaft
      fractures were managed with internal fixation. The rate of misdiagnosis for the
      Hoffa fractures was documented. Functions of the affected knees were evaluated
      according to the modified Hospital for Special Surgery (HSS) scores at two years
      follow-up. Femoral fractures were either transverse or composite in all three
      cases. Ipsilateral Hoffa fractures occurred at medial condyle in two cases, and
      lateral condyle in one case. Only one Hoffa fracture was identified
      preoperatively. All the femoral shaft fractures healed uneventfully. In the
      patient whose Hoffa fracture was correctly diagnosed, the modified HSS score was
      94. In another patient, whose Hoffa fracture was treated by a second operation,
      the modified HSS score was 93. And in the third case, who refused additional
      operation for the Hoffa fracture, the modified HSS score was only 70.
      Conclusively femoral shaft fracture can be associated with ipsilateral Hoffa
      fracture, especially in motorcycle accident. This type of injury is very rare and
      misdiagnosis is common.

PMID- 22152145
TI  - Neglected lateral process of talus fracture presenting as a loose body in tarsal
      canal.
AB  - Lateral process fractures of talus are rare injuries with a potential to cause
      significant morbidity if misdiagnosed. The appropriate management of these
      fractures is still controversial and only a few reports are avai- lable on this
      subject. We presented a case of a 37-year-old male with neglected fracture on the
      lateral process of talus which was misdiagnosed at the time of injury. The
      patient presented to 7 months after misdiagnosis with a chronic ankle pain. Our
      case is unique in the sense that it is a rare case of neglected fracture on the
      lateral process of talus which presented as a loose body in sinus tarsi. However,
      a surgery with an excision of the loose body presented a satis- factory outcome
      along with 2 years' follow-up. To our knowledge, it ought to be the first case
      reported in the English literature. Through this case report, we highlight the
      importance of high index of suspicion for such rare bony injuries while
      evaluating trauma to the lateral side of ankle and discuss the principles of
      management of these fractures.

PMID- 22152146
TI  - Children under stress - COMT genotype and stressful life events predict cortisol
      increase in an acute social stress paradigm.
AB  - Dopamine and norepinephrine are key regulators of cognitive and affective
      processes. The enzyme catechol-O-methyltransferase (COMT) catabolizes
      catecholamines and the COMT Val158Met polymorphism has been linked to several
      neuropsychiatric variables. Additionally, stressful life events (SLEs) contribute
      substantially to affective processes. We used the stress-induced activation of
      the hypothalamic-pituitary-adrenal axis to investigate the effects of COMT and
      SLEs on the cortisol response in 119 healthy children (8-12 yr). Saliva cortisol
      was measured during and after the Trier Social Stress Test for Children. SLEs
      were assessed with a standardized interview with one of the children's parents.
      Linear regression analysis revealed a significant effect for COMT, with Met
      allele carriers showing a higher cortisol response (beta=0.300, p=0.001). In
      turn, more SLEs lead to a less pronounced cortisol increase (beta=-0.192,
      p=0.029) probably indicating increased resilience. Our results further underscore
      the essential and differential role of genetic variation and environmental
      factors on stress responsivity.

PMID- 22152147
TI  - Effects of prenatal food and micronutrient supplementation on child growth from
      birth to 54 months of age: a randomized trial in Bangladesh.
AB  - BACKGROUND: There is a lack of information on the optimal timing of food
      supplementation to malnourished pregnant women and possible combined effects of
      food and multiple micronutrient supplementations (MMS) on their offspring's
      growth. We evaluated the effects of prenatal food and micronutrient interventions
      on postnatal child growth. The hypothesis was that prenatal MMS and early
      invitation to food supplementation would increase physical growth in the
      offspring during 0-54 months and a combination of these interventions would
      further improve these outcomes. METHODS: In the large, randomized MINIMat trial
      (Maternal and Infant Nutrition Interventions in Matlab), Bangladesh, 4436
      pregnant women were enrolled between November 2001 and October 2003 and their
      children were followed until March 2009. Participants were randomized into six
      groups comprising 30 mg Fe and 400 MUg folic acid (Fe30F), 60 mg Fe and 400 MUg
      folic acid (Fe60F) or MMS combined with either an early (immediately after
      identification of pregnancy) or a later usual (at the time of their choosing,
      i.e., usual care in this community) program invitation to food supplementation.
      The anthropometry of 3267 children was followed from birth to 54 months, and 2735
      children were available for analysis at 54 months. RESULTS: There were no
      differences in characteristics of mothers and households among the different
      intervention groups. The average birth weight was 2694 g and birth length was
      47.7 cm, with no difference among intervention groups. Early invitation to food
      supplementation (in comparison with usual invitation) reduced the proportion of
      stunting from early infancy up to 54 months for boys (p = 0.01), but not for
      girls (p = 0.31). MMS resulted in more stunting than standard Fe60F (p = 0.02).
      There was no interaction between the food and micronutrient supplementation on
      the growth outcome. CONCLUSIONS: Early food supplementation in pregnancy reduced
      the occurrence of stunting during 0-54 months in boys, but not in girls, and
      prenatal MMS increased the proportion of stunting in boys. These effects on
      postnatal growth suggest programming effects in early fetal life. TRIAL
      REGISTRATION NUMBER: ISRCTN: ISRCTN16581394.

PMID- 22152148
TI  - Fractionation statistics.
AB  - BACKGROUND: Paralog reduction, the loss of duplicate genes after whole genome
      duplication (WGD) is a pervasive process. Whether this loss proceeds gene by gene
      or through deletion of multi-gene DNA segments is controversial, as is the
      question of fractionation bias, namely whether one homeologous chromosome is more
      vulnerable to gene deletion than the other. RESULTS: As a null hypothesis, we
      first assume deletion events, on one homeolog only, excise a geometrically
      distributed number of genes with unknown mean u, and these events combine to
      produce deleted runs of length l, distributed approximately as a negative
      binomial with unknown parameter r, itself a random variable with distribution
      pi(.). A more realistic model requires deletion events on both homeologs
      distributed as a truncated geometric. We simulate the distribution of run lengths
      l in both models, as well as the underlying pi(r), as a function of u, and show
      how sampling l allows us to estimate u. We apply this to data on a total of 15
      genomes descended from 6 distinct WGD events and show how to correct the bias
      towards shorter runs caused by genome rearrangements. Because of the difficulty
      in deriving pi(.) analytically, we develop a deterministic recurrence to
      calculate each pi(r) as a function of u and the proportion of unreduced paralog
      pairs. CONCLUSIONS: The parameter u can be estimated based on run lengths of
      single-copy regions. Estimates of u in real data do not exclude the possibility
      that duplicate gene deletion is largely gene by gene, although it may sometimes
      involve longer segments.

PMID- 22152149
TI  - Observations on rift valley fever virus and vaccines in Egypt.
AB  - Rift Valley Fever virus (RVFV, genus: Phlebovirus, family: Bunyaviridae), is an
      arbovirus which causes significant morbidity and mortality in animals and humans.
      RVFV was introduced for the first time in Egypt in 1977. In endemic areas, the
      insect vector control and vaccination is considering appropriate measures if
      applied properly and the used vaccine is completely safe and the vaccination
      programs cover all the susceptible animals. Egypt is importing livestock and
      camels from the African Horn & the Sudan for human consumption. The imported
      livestock and camels were usually not vaccinated against RVFV. But in rare
      occasions, the imported livestock were vaccinated but with unknown date of
      vaccination and the unvaccinated control contacts were unavailable for laboratory
      investigations. Also, large number of the imported livestock and camels are often
      escaped slaughtering for breeding which led to the spread of new strains of FMD
      and the introduction of RVFV from the enzootic African countries. This article
      provide general picture about the present situation of RVFV in Egypt to help in
      controlling this important disease.

PMID- 22152150
TI  - Prevalence of post-traumatic stress disorder among adolescents after the Wenchuan
      earthquake in China.
AB  - BACKGROUND: The Wenchuan earthquake was a catastrophic earthquake in China. The
      aim of this study is to explore longitudinally the rates of post-traumatic stress
      disorder (PTSD) and depression in adolescents after the Wenchuan earthquake, and
      to identify independent predictors of PTSD. METHOD: PTSD and depression symptoms
      among adolescents at 6, 12 and 18 months after the Wenchuan earthquake were
      investigated using the PTSD Checklist Civilian Version and the Beck Depression
      Inventory (BDI). Subjects in this study included 548 high school student
      survivors in a local boarding high school. RESULTS: The rates of PTSD symptoms
      were 9.7%, 1.3% and 1.6% at the 6-, 12- and 18-month follow-ups, respectively.
      BDI scores were found to be the best predictor of severity of PTSD at 6, 12 and
      18 months. Gender was another variable contributing significantly to PTSD at 6
      and 12 months after the earthquake. In the 12-month follow-up, home damage was
      found to be a predictor of severity of PTSD symptoms. Being a child with siblings
      was found to be a predictor of severity of PTSD symptoms at 12 and 18 months
      after the earthquake. CONCLUSIONS: PTSD symptoms changed gradually at various
      stages after the earthquake. Depression symptoms were predictive of PTSD symptoms
      in the 18-month follow-up study. Other predictors of PTSD symptoms included
      female gender and being a child with siblings. The results of this study may be
      helpful for further mental health interventions for adolescents after
      earthquakes.

PMID- 22152151
TI  - Increased copy number for methylated maternal 15q duplications leads to changes
      in gene and protein expression in human cortical samples.
AB  - BACKGROUND: Duplication of chromosome 15q11-q13 (dup15q) accounts for
      approximately 3% of autism cases. Chromosome 15q11-q13 contains imprinted genes
      necessary for normal mammalian neurodevelopment controlled by a differentially
      methylated imprinting center (imprinting center of the Prader-Willi locus, PWS
      IC). Maternal dup15q occurs as both interstitial duplications and isodicentric
      chromosome 15. Overexpression of the maternally expressed gene UBE3A is predicted
      to be the primary cause of the autistic features associated with dup15q. Previous
      analysis of two postmortem dup15q frontal cortical samples showed heterogeneity
      between the two cases, with one showing levels of the GABAA receptor genes, UBE3A
      and SNRPN in a manner not predicted by copy number or parental imprint. METHODS:
      Postmortem human brain tissue (Brodmann area 19, extrastriate visual cortex) was
      obtained from 8 dup15q, 10 idiopathic autism and 21 typical control tissue
      samples. Quantitative PCR was used to confirm duplication status. Quantitative RT
      PCR and Western blot analyses were performed to measure 15q11-q13 transcript and
      protein levels, respectively. Methylation-sensitive high-resolution melting-curve
      analysis was performed on brain genomic DNA to identify the maternal:paternal
      ratio of methylation at PWS-IC. RESULTS: Dup15q brain samples showed a higher
      level of PWS-IC methylation than control or autism samples, indicating that
      dup15q was maternal in origin. UBE3A transcript and protein levels were
      significantly higher than control and autism in dup15q, as expected, although
      levels were variable and lower than expected based on copy number in some
      samples. In contrast, this increase in copy number did not result in consistently
      increased GABRB3 transcript or protein levels for dup15q samples. Furthermore,
      SNRPN was expected to be unchanged in expression in dup15q because it is
      expressed from the single unmethylated paternal allele, yet SNRPN levels were
      significantly reduced in dup15q samples compared to controls. PWS-IC methylation
      positively correlated with UBE3A and GABRB3 levels but negatively correlated with
      SNRPN levels. Idiopathic autism samples exhibited significantly lower GABRB3 and
      significantly more variable SNRPN levels compared to controls. CONCLUSIONS:
      Although these results show that increased UBE3A/UBE3A is a consistent feature of
      dup15q syndrome, they also suggest that gene expression within 15q11-q13 is not
      based entirely on copy number but can be influenced by epigenetic mechanisms in
      brain.

PMID- 22152154
TI  - Factors associated with body temperature of healthy Holstein dairy cows during
      the first 10 days in milk.
AB  - In this prospective observational study rectal and vaginal temperature of 82 (26
      primiparous, 56 multiparous) early post-partum healthy dairy cows that calved
      without intervention within 3 months and did not show clinical signs of
      infectious and metabolic diseases were continuously measured and evaluated for
      associations with plausible factors during the first 10 days in milk (DIM).
      During May, June and July mean (+/-SD) temperature humidity index (THI) was
      60.1+/-5; 66.8+/-5.6 and 74.2+/-4.3, respectively. Environmental conditions had a
      negligible effect on body temperature (BT) during May (P<0.05). During June and
      July, however, the ambient temperature and THI influenced BT (P<0.05).
      Furthermore, plausible factors like parity, DIM, months and time of day had an
      effect on BT (P<0.05). Overall, primiparous cows demonstrated 0.2 degrees C
      greater BT during the first 10 DIM than multiparous cows. The effect of parity,
      however, on BT varied between DIM according to month (P<0.001). During this 3
      month study period all cows demonstrated BT rhythms; however, the amplitude of BT
      increased from May to July (0.3 to 0.7 degrees C). A greater proportion of the
      vaginal temperature measurements exceeded a threshold tested (>=39.5 degrees C)
      during July (46.8%) than in June (33.9%) and May (19.3%). Overall the percentage
      of BT values above a threshold of >=39.5 degrees C was lower during the period
      6.00-10.00 compared with the remaining 20 h (P<0.05). Therefore this study
      concluded that the BT of healthy post-partum dairy cows during the period 1-10
      DIM post partum is greater compared with the reference range of 38.6 to 39.5
      degrees C reported by others and is influenced by parity, DIM, time of day and
      THI. When the association between BT and THI increased the reliability of
      threshold levels of BT (>=39.5 degrees C) decreased.

PMID- 22152152
TI  - Preliminary characterization of the oral microbiota of Chinese adults with and
      without gingivitis.
AB  - BACKGROUND: Microbial communities inhabiting human mouth are associated with oral
      health and disease. Previous studies have indicated the general prevalence of
      adult gingivitis in China to be high. The aim of this study was to characterize
      in depth the oral microbiota of Chinese adults with or without gingivitis, by
      defining the microbial phylogenetic diversity and community-structure using
      highly paralleled pyrosequencing. METHODS: Six non-smoking Chinese, three with
      and three without gingivitis (age range 21-39 years, 4 females and 2 males) were
      enrolled in the present cross-sectional study. Gingival parameters of
      inflammation and bleeding on probing were characterized by a clinician using the
      Mazza Gingival Index (MGI). Plaque (sampled separately from four different oral
      sites) and salivary samples were obtained from each subject. Sequences and
      relative abundance of the bacterial 16 S rDNA PCR-amplicons were determined via
      pyrosequencing that produced 400 bp-long reads. The sequence data were analyzed
      via a computational pipeline customized for human oral microbiome analyses.
      Furthermore, the relative abundances of selected microbial groups were validated
      using quantitative PCR. RESULTS: The oral microbiomes from gingivitis and healthy
      subjects could be distinguished based on the distinct community structures of
      plaque microbiomes, but not the salivary microbiomes. Contributions of community
      members to community structure divergence were statistically accessed at the
      phylum, genus and species-like levels. Eight predominant taxa were found
      associated with gingivitis: TM7, Leptotrichia, Selenomonas, Streptococcus,
      Veillonella, Prevotella, Lautropia, and Haemophilus. Furthermore, 98 species
      level OTUs were identified to be gingivitis-associated, which provided microbial
      features of gingivitis at a species resolution. Finally, for the two selected
      genera Streptococcus and Fusobacterium, Real-Time PCR based quantification of
      relative bacterial abundance validated the pyrosequencing-based results.
      CONCLUSIONS: This methods study suggests that oral samples from this patient
      population of gingivitis can be characterized via plaque microbiome by
      pyrosequencing the 16 S rDNA genes. Further studies that characterize serial
      samples from subjects (longitudinal study design) with a larger population size
      may provide insight into the temporal and ecological features of oral microbial
      communities in clinically-defined states of gingivitis.

PMID- 22152153
TI  - Prevalence and characteristics of antidepressant drug prescriptions in older
      Italian patients.
AB  - BACKGROUND: During last few decades, the proportion of elderly persons prescribed
      with antidepressants for the treatment of depression and anxiety has increased.
      The aim of this study was to evaluate prevalence of antidepressant prescription
      and related factors in elderly in-patients, as well as the consistency between
      prescription of antidepressants and specific diagnoses requiring these
      medications. METHODS: Thirty-four internal medicine and four geriatric wards in
      Italy participated in the Registro Politerapie SIMI-REPOSI study during 2008. In
      all, 1,155 in-patients, 65 years or older, were enrolled. Prevalence of the use
      of antidepressants was calculated at both admission and discharge. Logistic
      regression was used to evaluate the association between patients' characteristics
      (age, gender, Charlson Index, number of drugs, specific diseases, other
      psychotropic medications) and the prescription of antidepressants. RESULTS: The
      number of patients treated with antidepressant medication at hospital admission
      was 115 (9.9%) and at discharge 119 (10.3%). In a multivariate analysis, a higher
      number of drugs (OR = 1.2; 95% CI = 1.1-1.3), use of anxiolytic drugs (OR = 2.1;
      95% CI = 1.2-3.6 and OR = 3.8; 95% CI = 2.1-6.8), and a diagnosis of dementia (OR
      = 6.1; 95% CI = 3.1-11.8 and OR = 5.8; 95% CI = 3.3-10.3, respectively, at
      admission and discharge) were independently associated with antidepressant
      prescription. A specific diagnosis requiring the use of antidepressants was
      present only in 66 (57.4%) patients at admission and 76 (66.1%) at discharge.
      CONCLUSIONS: Antidepressants are commonly prescribed in geriatric patients,
      especially in those receiving multiple drugs, other psychotropic drugs, and those
      affected by dementia. There is an inconsistency between the prescription of
      antidepressants and a specific diagnosis that the hospitalization only slightly
      improves.

PMID- 22152155
TI  - Predictors of health status do not change over three-year periods and
      exacerbation makes difference in chronic obstructive pulmonary disease.
AB  - BACKGROUND: The association between disease markers and health status (HS)
      overtime is unclear. The aim of this study was to verify the predictors of HS at
      baseline and after three years in Chronic Obstructive Pulmonary Disease (COPD)
      patients. METHODS: Ninety-five consecutive COPD patients (66% male, age = 67 +/-
      9 y, FEV1 = 58 +/- 23%) underwent the following evaluations at baseline and after
      three years: body composition, pulse oximetry (SpO2), six-minute walk distance
      (6MWD), Modified edical Research Council dyspnea scale (MMRC) and Saint George's
      Respiratory Questionnaire (SGRQ). The Charlson comorbidity index and BODE index
      were calculated. COPD exacerbations during the follow-up were evaluated. At
      baseline, age, gender, smoking, SpO2, BODE index or its components (BMI, MMRC,
      FEV1 and 6MWD), and Charlson index were included in a multiple linear regression
      analysis with the baseline SGRQ total score as the dependent variable. After
      three years, we included the final values of the variables plus the number of
      exacerbations and the final SGRQ total score as the dependent variable. RESULTS:
      SGRQ total score (42 +/- 19% vs 44 +/- 19%; p = 0.041) and activity domain (52 +/
      21% vs 60 +/- 22%; p < 0.001) deteriorated during follow-up. At baseline, BODE
      index was selected as a predictor of SGRQ total score (R(2) = 0.46; p < 0.001);
      after three years, BODE index and age were the predictors (R(2) = 0.49; p <
      0.001). When the BODE index was replaced by its variables, MMRC was selected as
      the only variable associated with the SGRQ total score (R(2) = 0.58; p < 0.001).
      After three years, MMRC, FEV1 and number of exacerbations were selected as
      predictors of SGRQ total score (R(2) = 0.63; p < 0.001). CONCLUSION: HS
      deteriorated significantly over the three-year period and the predictors of HS do
      not change over time. BODE index and dyspnea were predictors at baseline and
      after three years. Exacerbation was also a predictor of HS after three years.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT00605540.

PMID- 22152156
TI  - Derivative spectrophotometric analysis of benzophenone (as an impurity) in
      phenytoin.
AB  - Three simple and rapid spectrophotometric methods were developed for detection
      and trace determination of benzophenone (the main impurity) in phenytoin bulk
      powder and pharmaceutical formulations. The first method, zero-crossing first
      derivative spectrophotometry, depends on measuring the first derivative trough
      values at 257.6 nm for benzophenone. The second method, zero-crossing third
      derivative spectrophotometry, depends on measuring the third derivative peak
      values at 263.2 nm. The third method, ratio first derivative spectrophotometry,
      depends on measuring the peak amplitudes of the first derivative of the ratio
      spectra (the spectra of benzophenone divided by the spectrum of 5.0 MUg/mL
      phenytoin solution) at 272 nm. The calibration graphs were linear over the range
      of 1-10 MUg/mL. The detection limits of the first and the third derivative
      methods were found to be 0.04 MUg/mL and 0.11 MUg/mL and the quantitation limits
      were 0.13 MUg/mL and 0.34 MUg/mL, respectively, while for the ratio derivative
      method, the detection limit was 0.06 MUg/mL and the quantitation limit was 0.18
      MUg/mL. The proposed methods were applied successfully to the assay of the
      studied drug in phenytoin bulk powder and certain pharmaceutical preparations.
      The results were statistically compared to those obtained using a polarographic
      method and were found to be in good agreement.

PMID- 22152157
TI  - Live cell division dynamics monitoring in 3D large spheroid tumor models using
      light sheet microscopy.
AB  - BACKGROUND: Multicellular tumor spheroids are models of increasing interest for
      cancer and cell biology studies. They allow considering cellular interactions in
      exploring cell cycle and cell division mechanisms. However, 3D imaging of cell
      division in living spheroids is technically challenging and has never been
      reported. RESULTS: Here, we report a major breakthrough based on the engineering
      of multicellular tumor spheroids expressing an histone H2B fluorescent nuclear
      reporter protein, and specifically designed sample holders to monitor live cell
      division dynamics in 3D large spheroids using an home-made selective-plane
      illumination microscope. CONCLUSIONS: As illustrated using the antimitotic drug,
      paclitaxel, this technological advance paves the way for studies of the dynamics
      of cell divion processes in 3D and more generally for the investigation of tumor
      cell population biology in integrated system as the spheroid model.

PMID- 22152158
TI  - Detailed genetic analysis of hemagglutinin-neuraminidase glycoprotein gene in
      human parainfluenza virus type 1 isolates from patients with acute respiratory
      infection between 2002 and 2009 in Yamagata prefecture, Japan.
AB  - BACKGROUND: Human parainfluenza virus type 1 (HPIV1) causes various acute
      respiratory infections (ARI). Hemagglutinin-neuraminidase (HN) glycoprotein of
      HPIV1 is a major antigen. However, the molecular epidemiology and genetic
      characteristics of such ARI are not exactly known. Recent studies suggested that
      a phylogenetic analysis tool, namely the maximum likelihood (ML) method, may be
      applied to estimate the evolutionary time scale of various viruses. Thus, we
      conducted detailed genetic analyses including homology analysis, phylogenetic
      analysis (using both the neighbor joining (NJ) and ML methods), and analysis of
      the pairwise distances of HN gene in HPIV1 isolated from patients with ARI in
      Yamagata prefecture, Japan. RESULTS: A few substitutions of nucleotides in the
      second binding site of HN gene were observed among the present isolates. The
      strains were classified into two major clusters in the phylogenetic tree by the
      NJ method. Another phylogenetic tree constructed by the ML method showed that the
      strains diversified in the late 1980s. No positively selected sites were found in
      the present strains. Moreover, the pairwise distance among the present isolates
      was relatively short. CONCLUSIONS: The evolution of HN gene in the present HPIV1
      isolates was relatively slow. The ML method may be a useful phylogenetic method
      to estimate the evolutionary time scale of HPIV and other viruses.

PMID- 22152159
TI  - Hepatitis B and C viral infections among blood donors. A retrospective study from
      a rural community of Ghana.
AB  - BACKGROUND: Infection by Hepatitis B virus (HBV) and Hepatitis C virus (HCV)
      cause serious mortality, morbidity and financial burden and are thus a major
      global health problem. The study was conducted to investigate the prevalence of
      Hepatitis B and C infections and co-infections among blood donors in a rural
      community of Ghana.This was a retrospective study conducted at the Agogo
      Presbyterian Hospital in the Asanti Akim North District of Ghana to investigate
      the prevalence of these infections over a three year period among 2773 blood
      donors. Males constituted a larger proportion of the study population (92.2%).
      Majority of the study population (43.9%) were within 26-35 age group. The disease
      prevalence was calculated at a 95% confidence interval. FINDINGS: The prevalence
      of Hepatitis B viral (HBV) infection was highest in females- 21.4% (95% CI: 11.6
      34.4) in 2006 than males in the same year- 13.2% (95% CI: 10.8-15.9). Hepatitis C
      viral (HCV) infection was highest among males- 11.6% (95% CI: 9.5-13.8) in 2007.
      HBV and HCV co-infection was higher in males- 2.6% (95% CI: 1.6-3.8) than females
      1.3% (95% CI: 0-7.0) in 2007. The overall prevalence of HBV and HCV was 13.8%
      (95% CI: 11.4- 16.4) and 9.4% (95% CI: 7.4-11.6) respectively in 2006. The rate
      of co-infection of HBV and HCV however increased from 1.6% (95% CI: 0.8-2.7) in
      2006 to 2.2% (95% CI: 1.3-3.2) in 2008 in males and from 0% (95% CI: 0-6.4) in
      2006 to 1.2% (95% CI: 0-6.5) in 2008 in females. CONCLUSION: The single
      infections of HBV and HCV reduced but co-infection of these transfusion
      transmitted infections increased. Measures such as more sensitive techniques for
      effective diagnosis and sanitary education to enlighten the population must be
      implemented.

PMID- 22152161
TI  - Quality in quality improvement research--a new benchmark.
AB  - CITATION: Scales DC, Dainty K, Hales B, Pinto R, Fowler RA, Adhikari NK,
      Zwarenstein M: A multifaceted intervention for quality improvement in a network
      of intensive care units: a cluster randomized trial. JAMA 2011, 305:363-72.
      CONTEXT: Evidence-based practices improve intensive care unit (ICU) outcomes, but
      eligible patients may not receive them. Community hospitals treat most critically
      ill patients but may have few resources to devote to quality improvement.
      OBJECTIVE: To determine the effectiveness of a multicenter quality improvement
      program to increase delivery of 6 evidence-based ICU practices. DESIGN, SETTING,
      AND PARTICIPANTS: Pragmatic, cluster-randomized trial among 15 community hospital
      ICUs in Ontario, Canada. A total of 9269 admissions occurred during the trial
      (November 2005 to October 2006) and 7141 admissions during a decay-monitoring
      period (December 2006 to August 2007). INTERVENTION: The authors implemented a
      videoconference-based forum including audit and feedback, expert-led educational
      sessions, and dissemination of algorithms to sequentially improve delivery of 6
      practices. The ICUs were randomized into 2 groups. Each group received this
      intervention, targeting a new practice every 4 months, while acting as control
      for the other group, in which a different practice was targeted in the same
      period. MAIN OUTCOMES: The primary outcome was the summary ratio of odds ratios
      (ORs) for improvement in adoption (determined by daily data collection) of all 6
      practices during the trial in intervention vs control ICUs. RESULTS: Overall,
      adoption of the targeted practices was greater in intervention ICUs than in
      controls (summary ratio of ORs, 2.79; 95% confidence interval [CI], 1.00-7.74).
      Improved delivery in intervention ICUs was greatest for semi recumbent
      positioning to prevent ventilator-associated pneumonia (90.0% of patient-days in
      last month vs. 50.0% in first month; OR, 6.35; 95% CI, 1.85-21.79) and
      precautions to prevent catheter-related bloodstream infection (70.0% of patients
      receiving central lines vs. 10.6%; OR, 30.06; 95% CI, 11.00-82.17). Adoption of
      other practices, many with high baseline adherence, changed little. CONCLUSION:
      In a collaborative network of community ICUs, a multi-faceted quality improvement
      intervention improved adoption of care practices.

PMID- 22152160
TI  - Healthy Eating Index scores associated with symptoms of depression in Cuban
      Americans with and without type 2 diabetes: a cross sectional study.
AB  - BACKGROUND: Low diet quality and depression symptoms are independently associated
      with poor glycemic control in subjects with type 2 diabetes (T2D); however, the
      relationship between them is unclear. The aim of this study was to determine the
      association between diet quality and symptoms of depression among Cuban-Americans
      with and without T2D living in South Florida. METHODS: Subjects (n = 356) were
      recruited from randomly selected mailing list. Diet quality was determined using
      the Healthy Eating Index-2005 (HEI-05) score. Symptoms of depression were
      assessed using the Beck Depression Inventory (BDI). Both linear and logistic
      regression analyses were run to determine whether or not these two variables were
      related. Symptoms of depression was the dependent variable and independent
      variables included HEI-05, gender, age, marital status, BMI, education level,
      A1C, employment status, depression medication, duration of diabetes, and diabetes
      status. Analysis of covariance was used to test for interactions among variables.
      RESULTS: An interaction between diabetes status, gender and HEI-05 was found (P =
      0.011). Among males with a HEI-05 score <= 55.6, those with T2D had a higher mean
      BDI score than those without T2D (11.6 vs. 6.6 respectively, P = 0.028). Among
      males and females with a HEI-05 score <= 55.6, females without T2D had a higher
      mean BDI score compared to males without T2D (11.0 vs. 6.6 respectively, P =
      0.012) CONCLUSIONS: Differences in symptoms of depression according to diabetes
      status and gender are found in Cuban-Americans with low diet quality.

PMID- 22152162
TI  - Neuroinflammation in Alzheimer's disease wanes with age.
AB  - BACKGROUND: Inflammation is a prominent feature in Alzheimer's disease (AD). It
      has been proposed that aging has an effect on the function of inflammation in the
      brain, thereby contributing to the development of age-related diseases like AD.
      However, the age-dependent relationship between inflammation and clinical
      phenotype of AD has never been investigated. METHODS: In this study we have
      analysed features of the neuroinflammatory response in clinically and
      pathologically confirmed AD and control cases in relation to age (range 52-97
      years). The mid-temporal cortex of 19 controls and 19 AD cases was assessed for
      the occurrence of microglia and astrocytes by immunohistochemistry using
      antibodies directed against CD68 (KP1), HLA class II (CR3/43) and glial
      fibrillary acidic protein (GFAP). RESULTS: By measuring the area density of
      immunoreactivity we found significantly more microglia and astrocytes in AD cases
      younger than 80 years compared to older AD patients. In addition, the presence of
      KP1, CR3/43 and GFAP decreases significantly with increasing age in AD.
      CONCLUSION: Our data suggest that the association between neuroinflammation and
      AD is stronger in relatively young patients than in the oldest patients. This age
      dependent relationship between inflammation and clinical phenotype of AD has
      implications for the interpretation of biomarkers and treatment of the disease.

PMID- 22152163
TI  - Role of microRNAs in immunity and organ transplantation.
AB  - Organ transplantation has evolved rapidly and there is now widespread use of
      donated organs for the treatment of end-stage organ failure. Although the
      therapeutic options achieving long-term graft survival have improved, acute and
      chronic rejections are still a major problem. Studies to identify noninvasive
      biomarkers for rejection and underlying molecular events have increased
      significantly in the past decade, but a major breakthrough is still missing. The
      recent discovery of small regulatory RNA molecules (microRNAs) resulted in a new
      and improved understanding of the mechanisms of gene regulation and also led to
      the development of the first new microRNA (miRNA)-based therapies. miRNAs are
      endogenous, single-stranded RNAs consisting of about 19-25 noncoding nucleotides,
      which have an important role in regulating gene expression. Additionally,
      circulating miRNAs that might be useful as novel disease biomarkers were
      detected. Here, we summarise current knowledge about the role of miRNAs in
      immunology and transplantation medicine and their role as potential biomarkers.
      We also focus on the molecular mechanisms and therapeutic implications of the use
      of miRNA-based therapeutic strategies to improve long-term allograft survival.

PMID- 22152164
TI  - Assuring the patient centeredness of patient-reported outcomes: content validity
      in medical product development and comparative effectiveness research.

PMID- 22152165
TI  - Content validity--establishing and reporting the evidence in newly developed
      patient-reported outcomes (PRO) instruments for medical product evaluation: ISPOR
      PRO good research practices task force report: part 1--eliciting concepts for a
      new PRO instrument.
AB  - The importance of content validity in developing patient reported outcomes (PRO)
      instruments is stressed by both the US Food and Drug Administration and the
      European Medicines Agency. Content validity is the extent to which an instrument
      measures the important aspects of concepts that developers or users purport it to
      assess. A PRO instrument measures the concepts most significant and relevant to a
      patient's condition and its treatment. For PRO instruments, items and domains as
      reflected in the scores of an instrument should be important to the target
      population and comprehensive with respect to patient concerns. Documentation of
      target population input in item generation, as well as evaluation of patient
      understanding through cognitive interviewing, can provide the evidence for
      content validity. Developing content for, and assessing respondent understanding
      of, newly developed PRO instruments for medical product evaluation will be
      discussed in this two-part ISPOR PRO Good Research Practices Task Force Report.
      Topics include the methods for generating items, documenting item development,
      coding of qualitative data from item generation, cognitive interviewing, and
      tracking item development through the various stages of research and preparing
      this tracking for submission to regulatory agencies. Part 1 covers elicitation of
      key concepts using qualitative focus groups and/or interviews to inform content
      and structure of a new PRO instrument. Part 2 covers the instrument development
      process, the assessment of patient understanding of the draft instrument using
      cognitive interviews and steps for instrument revision. The two parts are meant
      to be read together. They are intended to offer suggestions for good practices in
      planning, executing, and documenting qualitative studies that are used to support
      the content validity of PRO instruments to be used in medical product evaluation.

PMID- 22152166
TI  - Content validity--establishing and reporting the evidence in newly developed
      patient-reported outcomes (PRO) instruments for medical product evaluation: ISPOR
      PRO Good Research Practices Task Force report: part 2--assessing respondent
      understanding.
AB  - The importance of content validity in developing patient reported outcomes (PRO)
      instruments is stressed by both the US Food and Drug Administration and the
      European Medicines Agency. Content validity is the extent to which an instrument
      measures the important aspects of concepts developers or users purport it to
      assess. A PRO instrument measures the concepts most relevant and important to a
      patient's condition and its treatment. For PRO instruments, items and domains as
      reflected in the scores of an instrument should be important to the target
      population and comprehensive with respect to patient concerns. Documentation of
      target population input in item generation, as well as evaluation of patient
      understanding through cognitive interviewing, can provide the evidence for
      content validity. Part 1 of this task force report covers elicitation of key
      concepts using qualitative focus groups and/or interviews to inform content and
      structure of a new PRO instrument. Building on qualitative interviews and focus
      groups used to elicit concepts, cognitive interviews help developers craft items
      that can be understood by respondents in the target population and can ultimately
      confirm that the final instrument is appropriate, comprehensive, and
      understandable in the target population. Part 2 details: 1) the methods for
      conducting cognitive interviews that address patient understanding of items,
      instructions, and response options; and 2) the methods for tracking item
      development through the various stages of research and preparing this tracking
      for submission to regulatory agencies. The task force report's two parts are
      meant to be read together. They are intended to offer suggestions for good
      practice in planning, executing, and documenting qualitative studies that are
      used to support the content validity of PRO instruments to be used in medical
      product evaluation.

PMID- 22152167
TI  - Prioritizing pharmacogenetic research: a value of information analysis of CYP2D6
      testing to guide breast cancer treatment.
AB  - OBJECTIVES: To demonstrate how value of information (VOI) analysis can be used to
      establish research priorities regarding the use of pharmacogenetic tests using
      CYP2D6 testing to select adjuvant hormonal therapy in early stage breast cancer
      as a case study. METHODS: The following four treatment pathways are compared in a
      Markov model: tamoxifen treatment; CYP2D6 test and treat homozygous and
      heterozygous wild type patients (wt/wt; wt/*4) with tamoxifen and *4/*4 patients
      with anastrozole (HetTam); CYP2D6 test and treat homozygous wild type patients
      with tamoxifen and others with anastrozole (HomTam); and anastrozole treatment.
      Pharmacogenetic testing efficacy is estimated by synthesizing randomized
      controlled trial data comparing tamoxifen to anastrozole with observational data
      linking CYP2D6 genotype to tamoxifen outcomes. RESULTS: In order of increasing
      effectiveness the comparators are tamoxifen, HetTam, HomTam, anastrozole. Health
      outcomes for test and treatment strategies are highly uncertain. Differences in
      comparator costs depend on assumptions made regarding anastrozole patent expiry.
      The expected value of a decision taken with perfect information is L69 to L106
      million (pound sterling) for the United Kingdom depending on patent expiry
      assumptions and the acceptable cost-effectiveness threshold. The most valuable
      research (VOI L53-L82 million) elucidates the relationship between CYP2D6
      genotype and tamoxifen effectiveness. It is uncertain whether values of other
      research designs would exceed their costs. CONCLUSIONS: Retrospective analysis of
      one of the large adjuvant aromatase inhibitor trials is warranted to better
      understand any association between CYP2D6 genotype and tamoxifen outcomes. VOI
      approaches may be helpful for prioritising evidence needs and structuring
      coverage with evidence development agreements for pharmacogenetics.

PMID- 22152168
TI  - Cost-effectiveness of lanthanum carbonate versus sevelamer hydrochloride for the
      treatment of hyperphosphatemia in patients with end-stage renal disease: a US
      payer perspective.
AB  - OBJECTIVE: To assess the cost-effectiveness of lanthanum carbonate (LC) versus
      sevelamer hydrochloride (SH) as a treatment for hyperphosphatemia in end-stage
      renal disease (ESRD) patients. METHODS: A Markov model was developed to estimate
      health outcomes; quality-adjusted life years (QALYs) and life-years saved (LYS),
      as well as associated costs. The model incorporated patient-level data from a
      randomized head-to-head crossover study that compared the reduction of serum
      phosphorus using LC and SH for 4 weeks each. The model included patients
      previously treated with calcium-based binders. Both the intent-to-treat (ITT)
      population and the cohort of patients who completed treatment in both periods of
      the study (i.e., completer population) were assessed. The baseline risks of
      cardiovascular disease (CVD), all-cause mortalities for CVD, and non-CVD patients
      were derived from a large US renal database. Patient outcomes were modeled for 10
      years, and incremental cost-effectiveness ratios (ICERs) were calculated for LC
      relative to SH. Deterministic and probabilistic sensitivity analyses (PSA) were
      performed to test the robustness of the base-case model. RESULTS: For the ITT
      population, the ICERs of LC versus SH were $24,724/QALY and $15,053/LYS,
      respectively (in US dollars). When the completer population was considered, the
      ICERs of LC versus SH were $15,285/QALY and $9,337/LYS (Table 2), respectively.
      The PSA indicated 61.9% and 85.8% probabilities for ITT and completer populations
      of LC being cost-effective at the $50,000/QALY willingness-to-pay threshold,
      respectively. CONCLUSION: LC is a cost-effective strategy compared with SH in the
      treatment of ESRD patients with hyperphosphatemia who were previously treated
      with calcium-based binders. Sensitivity analyses demonstrated the robustness of
      the pharmacoeconomic model.

PMID- 22152169
TI  - Cost-utility analyses of diagnostic laboratory tests: a systematic review.
AB  - OBJECTIVE: To review and evaluate the literature of cost-utility analyses (CUAs)
      regarding diagnostic laboratory testing. METHODS: We reviewed all articles
      related to diagnostic laboratory testing in the Tufts Medical Center Cost
      Effectiveness Analysis Registry (www.cearegistry.org), which contains detailed
      information on over 2000 published CUAs through 2008. We analyzed the extent to
      which the studies adhered to recommended practices for conducting and reporting
      cost-effectiveness analyses. We also recorded whether the studies contained
      information on diagnostic test accuracy and costs, and whether any account was
      taken of potential benefits or harms of testing that are unrelated to subsequent
      treatment, such as the reassurance value of testing. RESULTS: We identified 141
      published CUAs pertaining to diagnostic laboratory testing published through 2008
      which contained 433 separate incremental cost-effectiveness ratios. Prior to
      2000, there were only 20 CUAs published, but the number averaged 13.4 annually
      thereafter. Most studies focused on hematology/oncology (n = 42, 30%) and
      obstetrics/gynecology (n = 36, 26%) applications. Approximately 63% (n = 89) of
      studies clearly reported information about the accuracy of the test, but only 10%
      (n = 14) mentioned test safety or possible risks. A small number (n = 10, 7%)
      mentioned or considered the potential value or harm of testing unrelated to
      treatment consequences. Over 55% of the reported incremental cost-effectiveness
      ratios (ICERs) were either dominant (more quality-adjusted life years for less
      cost), or below $50,000 per quality-adjusted life years gained (in 2008 US
      dollars). CONCLUSION: The number of CUAs investigating laboratory diagnostic
      testing has increased substantially with applications to diverse clinical areas.
      The literature reveals many areas in which testing represents good value for
      money. The vast majority of studies have not considered preferences for test
      information unrelated to treatment consequences.

PMID- 22152170
TI  - Cost-effectiveness analysis of a universal infant immunization program with
      meningococcal C conjugate vaccine in Brazil.
AB  - OBJECTIVE: To analyze the cost-effectiveness of a meningococcal C vaccination
      program in Brazil. METHODS: A hypothetical cohort of 3,194,038 children born in
      Brazil in 2006 was followed for 10 years. A decision tree model was developed
      using the TreeAge Pro 2007 software program to compare universal infant
      vaccination with the current program. Epidemiological and cost estimates were
      based on data retrieved from National Health Information Systems and the
      literature. The analysis was conducted from the public health care system and
      societal perspectives. Costs are expressed in 2006 Brazilian reals (R$). RESULTS:
      At 94% coverage, the program would avoid 1,218 cases, 210 deaths, and 14,473 life
      years lost, a reduction of, respectively, 45%, 44%, and 44%, for the 10-year
      period. Vaccination costs of R$320.9 million would not be offset by R$4 to R$7.9
      million decreases in disease treatment costs. A national vaccination program
      would cost R$21,620 per life-year saved from the perspective of the health-care
      system and R$21,896 per life-year saved from society's perspective. Results were
      most sensitive to case fatality rate, disease incidence, and vaccine cost.
      CONCLUSIONS: A universal childhood vaccination program against meningococcal C
      proved to be a cost-effective strategy, supporting the recent decision of the
      Brazilian government. These results could contribute to defining the most
      favorable price of the vaccine and to monitoring its impact on the population.

PMID- 22152171
TI  - Cost-effectiveness of the introduction of a pre-erythrocytic malaria vaccine into
      the expanded program on immunization in sub-Saharan Africa: analysis of
      uncertainties using a stochastic individual-based simulation model of Plasmodium
      falciparum malaria.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of introducing the RTS,S malaria
      vaccine into the Expanded Programme on Immunization (EPI) in Sub-Saharan Africa
      (SSA), the contributions of different sources of uncertainty, and the associated
      expected value of perfect information (EVPI). METHODS: Vaccination was simulated
      in populations of 100,000 people at 10 different entomological inoculation rates
      (EIRs), using an existing stochastic model and a 10-year time horizon.
      Incremental cost-effectiveness ratios (ICERs) and EVPI were computed from
      weighted averages of outputs using two different assignments of the EIR
      distribution in 2007. Uncertainty was evaluated by resampling of epidemiological,
      vaccination, and health systems model parameters. RESULTS: Health benefits were
      predicted consistently only at low transmission, and program costs always
      substantially exceeded case management savings. Optimal cost-effectiveness was at
      EIR of about 10 infectious bites per annum (ibpa). Main contributors to ICER
      uncertainty were uncertainty in transmission intensity, price per vaccine dose,
      decay rate of the vaccine effect, degree of homogeneity in host response, and
      some epidemiological model parameters. Other health system costs were
      unimportant. With a ceiling ratio of 207 international dollars per disability
      adjusted life-year averted, 52.4% of parameterizations predicted cost
      effectiveness in the primary analysis. CONCLUSIONS: Cost-effectiveness of RTS,S
      will be maximal in low endemicity settings (EIR 2-20 ibpa). Widespread deployment
      of other transmission-reducing interventions will thus improve cost
      effectiveness, suggesting a selective introduction strategy. EVPI is substantial.
      Accrual of up-to-date information on local endemicity to guide deployment
      decisions would be highly efficient.

PMID- 22152172
TI  - Developing and applying a stochastic dynamic population model for chronic
      obstructive pulmonary disease.
AB  - OBJECTIVES: To develop a stochastic population model of disease progression in
      chronic obstructive pulmonary disease (COPD) that includes the effects of COPD
      exacerbations on health-related quality of life, costs, disease progression, and
      mortality and can be used to assess the effects of a wide range of interventions.
      METHODS: The model is a multistate Markov model with time varying transition
      rates specified by age, sex, smoking status, COPD disease severity, and/or
      exacerbation type. The model simulates annual changes in COPD prevalence due to
      COPD incidence, exacerbations, disease progression (annual decline in the forced
      expiratory volume in 1 second as percentage of the predicted value), and
      mortality. The main outcome variables are quality-adjusted life years, total
      exacerbations, and COPD-related health care costs. Exacerbation-related input
      parameters were based on quantitative meta-analysis. All important model
      parameters are entered into the model as probability distributions. To illustrate
      the potential use of the model, costs and effects were calculated for 3-year
      implementation of three different COPD interventions, one pharmacologic, one on
      smoking cessation, and one on pulmonary rehabilitation using a time horizon of 10
      years for reporting outcomes. RESULTS: Compared with minimal treatment the
      cost/quality-adjusted life year was ?8,300 for the pharmacologic intervention,
      ?10,800 for the smoking cessation therapy, ?8,700 for the combination of the
      pharmacologic intervention and the smoking cessation therapy, and ?17,200 for the
      pulmonary rehabilitation program. The probability of the interventions to be cost
      effective at a ceiling ratio of ?20,000 varied from 58% to 100%. CONCLUSIONS: The
      COPD model provides policy makers with information about the long-term costs and
      effects of interventions over the entire chain of care, from primary prevention
      to care for very severe COPD and includes uncertainty around the outcomes.

PMID- 22152173
TI  - Economics of switching to second-line antiretroviral therapy with
      lopinavir/ritonavir in Africa: estimates based on DART trial results and costs
      for Uganda and Kenya.
AB  - BACKGROUND: Substantial immunological improvement has been reported for HIV
      infected patients who switch from a failing regimen to a protease inhibitor
      regimen with Lopinavir/ritonavir (LPV/r). We use decision analysis modeling to
      estimate health and economic consequences expected from this switch. METHODS: A
      Markov model combined best evidence for CD4(+) T-cell response, infectious
      disease events, death rates, and quality of life for African populations with
      Kenyan and Ugandan data on drug and medical care costs. We estimate the
      incremental cost-effectiveness ratio of switching to an LPV/r-based regimen
      versus remaining on a failed first antiretroviral (ARV) regimen or discontinuing
      all ARV drugs. The model assumes concurrent use of cotrimoxazole, and 4% annual
      loss to follow-up. Local effects due to prevalence of malaria and tuberculosis
      are included in the model. Sensitivity analysis examines the effects of varying
      disease, ARV therapy and CD4(+) T-cell cost, and ART discontinuation assumptions.
      RESULTS: The base model estimates an improvement of 20 months in average survival
      for the LPV/r group. The respective LPV/r ICER for Kenya is $1483 per quality
      adjusted life year (QALY) compared to $1673/QALY for Uganda. The ICERs increase
      to $1517 and $1707, respectively, if CD4(+) T-cell tests cost $25. The model
      comparing switching to LPV/r to discontinuing all ARV drugs decreases both costs
      and benefits proportionally for the treatment groups. CONCLUSION: The estimates
      are clearly below the most stringent World Health Organization benchmark for cost
      effectiveness for Kenya and within the acceptable range of cost-effectiveness for
      Uganda. Thus, the switch to second-line therapy with LPV/r in these countries
      appears to be a cost-effective use of resources.

PMID- 22152174
TI  - When evaluating parameter uncertainty is not enough: the case of dasatinib and
      nilotinib for imatinib-resistant chronic myeloid leukemia.

PMID- 22152175
TI  - Cost-effectiveness of dasatinib and nilotinib for imatinib-resistant or 
      intolerant chronic phase chronic myeloid leukemia.
AB  - OBJECTIVES: To estimate the cost-effectiveness of dasatinib and nilotinib
      compared with high-dose imatinib for people with chronic phase chronic myeloid
      leukemia, which are resistant to normal-dose imatinib and compared with
      interferon-alpha for people intolerant to imatinib, from the perspective of the
      UK National Health Service. METHODS: An an area under the curve partitioned
      survival model was developed to estimate the cost-effectiveness of dasatinib and
      nilotinib. Clinical effectiveness evidence was taken mostly from single-arm
      trials. RESULTS: Both progression-free survival and overall survival are highly
      uncertain. In the base case, patients take nilotinib for much less time than
      dasatinib. Nilotinib is expected to dominate high-dose imatinib, yielding
      slightly more (0.32) quality-adjusted life years (QALYs) at slightly less cost
      (L11,100 [pound sterling]) per person. Dasatinib is predicted to provide slightly
      more (0.53) QALYs at substantially greater cost (L48,900), yielding a very high
      incremental cost-effectiveness ratio of L91,500 QALY against high-dose imatinib.
      Cost-effectiveness, however, changes radically under the plausible assumption
      that the drugs are taken for the same time. For people intolerant to imatinib,
      nilotinib is expected to yield an incremental cost-effectiveness ratio of
      L104,700/QALY, and dasatinib L82,600/QALY compared with interferon-alpha.
      Further, both drugs represent poor value for money for a range of plausible
      structural assumptions. CONCLUSIONS: The model should be viewed as an exploratory
      analysis of the cost-effectiveness of dasatinib and nilotinib because it relies
      on many assumptions. Whilst clinical data remains immature, the cost
      effectiveness of dasatinib and nilotinib for imatinib-resistant people is highly
      uncertain. Both nilotinib and dasatinib are highly unlikely to be cost-effective
      versus interferon-alpha for people intolerant to imatinib.

PMID- 22152176
TI  - Structural frameworks and key model parameters in cost-effectiveness analyses for
      current and future treatments of chronic hepatitis C.
AB  - OBJECTIVES: Published economic evaluations have reported available treatments for
      chronic hepatitis C to be cost-effective as part of the current approach to
      disease management, but as standards of care evolve, their approach to modeling
      should be reconsidered. This study aimed to review structural frameworks and key
      model parameters as reported in current economic evaluations for treatments for
      chronic hepatitis C, and model the impact of variability across parameters on
      results. METHODS: A systematic review of studies published from 2000 to 2011 was
      performed. Studies were retrieved from five electronic databases using relevant
      search strategies. Model structures, disease progression rates, utilities, and
      costs were extracted from included studies, and were qualitatively reviewed and
      incorporated into a cost-utility model. RESULTS: Thirty-four studies were
      appropriate for data extraction. A common pathway of six disease states was
      identified. In some studies the early disease stages and/or the decompensated
      cirrhosis state were further subdivided. Large variability in values used for
      disease progression rates, utilities, and costs were identified. When
      incorporated into a model, incremental cost-effectiveness ratios (ICERs) varied:
      in the least favorable scenario, peginterferon plus ribavirin was dominated by
      interferon plus ribavirin; and in the most favorable scenario, peginterferon plus
      ribavirin dominated interferon plus ribavirin ($8,544 per quality-adjusted life
      year [QALY]; costs are given in 2008 US dollar amounts). Using mean values the
      ICER was $15,198 per QALY. CONCLUSIONS: Current models use a simplistic structure
      resulting from the lack of available data reflecting patient heterogeneity. Key
      model parameters are currently based on a small number of studies and the
      variability across these values can affect the interpretation of results.

PMID- 22152177
TI  - Some cautions on the use of instrumental variables estimators in outcomes
      research: how bias in instrumental variables estimators is affected by instrument
      strength, instrument contamination, and sample size.
AB  - OBJECTIVES: To examine the performance of instrumental variables (IV) and
      ordinary least squares (OLS) regression under a range of conditions likely to be
      encountered in empirical research. METHODS: A series of simulation analyses are
      carried out to compare estimation error between OLS and IV when the independent
      variable of interest is endogenous. The simulations account for a range of
      situations that may be encountered by researchers in actual practice-varying
      degrees of endogeneity, instrument strength, instrument contamination, and sample
      size. The intent of this article is to provide researchers with more intuition
      with respect to how important these factors are from an empirical standpoint.
      RESULTS: Notably, the simulations indicate a greater potential for inferential
      error when using IV than OLS in all but the most ideal circumstances.
      CONCLUSIONS: Researchers should be cautious when using IV methods. These methods
      are valuable in testing for the presence of endogeneity but only under the most
      ideal circumstances are they likely to produce estimates with less estimation
      error than OLS.

PMID- 22152178
TI  - Methods for using data abstracted from medical charts to impute longitudinal
      missing data in a clinical trial.
AB  - OBJECTIVE: To describe a method for imputing missing follow-up blood pressure
      data in a clinical hypertension trial using blood pressures abstracted from
      medical charts. METHODS: We tested a two-step method. In the first, a
      longitudinal mixed-effects model was estimated on blood pressures abstracted from
      medical charts. In the second, the patient-specific fitted values from this model
      at follow-up were used to impute blood pressures missing at follow-up in the
      trial. Simulations that imposed alternative missing data mechanisms on observed
      trial data were used to compare this approach to imputation approaches that do
      not incorporate data from charts. RESULTS: For data that are missing at random,
      incorporating the fitted values from chart-based longitudinal models leads to
      estimates of the trial-based blood pressures that are unbiased and have lower
      mean squared deviation than do blood pressures imputed without the chart-based
      data. For data that are missing not at random, incorporating fitted values
      ameliorates but does not eliminate the inherent missing data bias. CONCLUSIONS:
      Incorporating chart data into an imputation algorithm via the use of longitudinal
      mixed-effects model is an efficient way to impute longitudinal data that are
      missing from a randomized trial.

PMID- 22152179
TI  - Toward identifying the causes and combinations of causes increasing the risks of
      nonadherence to medical regimens: combined results of two German self-report
      surveys.
AB  - OBJECTIVES: This study aimed to identify the causes of the nonadherence (NA) of
      German patients to their prescribed medication. In the course of the
      investigation, the NA risk profiles resulting from the combination of the various
      causes were identified. METHODS: Two cross-sectional surveys with a total of 1517
      patients (comprising 1177 patients contacted by telephone and forming survey 1
      and a different set of 340 patients interviewed in-depth and face-to-face forming
      survey 2) were conducted. Self-reported NA was measured by the generic Morisky
      Medication Adherence Scale (MMAS). Survey 1 used a four-item MMAS and Survey 2 an
      eight-item MMAS. RESULTS: Approximately 35% to 40% of the patients can be
      described as nonadherent. In survey 1, a few causes explain the NA (chronic
      disease, younger age, and fewer medications required to be taken). The more
      detailed survey 2 shows that the existence of intentional NA has considerably
      more influence than any other causal factors. Positive medication beliefs, a
      positive mood, and a good patient-doctor relationship reduce the NA risk.
      Furthermore, patients who are easily able to recognize the correct medication, as
      evidenced by ability to correctly identify the packaging, have a reduced NA
      probability. Concerning additive risk, patients who are chronically ill but
      display no other causes of risk have an NA probability of 10.4%. By contrast, in
      patients displaying all the identified causes of risk, the rate increases to
      93.9%. CONCLUSIONS: About one-third of patients can be classified as nonadherent.
      Intentional/medication-based NA causal factors explain the NA considerably better
      than do socioeconomics. The existence of more than one cause of risk considerably
      increases the NA risk of a patient.

PMID- 22152180
TI  - Response burden and questionnaire length: is shorter better? A review and meta
      analysis.
AB  - BACKGROUND: Response burden is often defined as the effort required by the
      patient to answer a questionnaire. A factor that has been proposed to affect the
      response burden is questionnaire length, and this burden is manifested in, for
      example, response rate. Even though response burden is frequently mentioned as a
      reason for abridging questionnaires, evidence to support the notion that shorter
      instruments are preferable is limited. OBJECTIVES: This study aimed to
      accumulate, analyze, and discuss evidence regarding the association between
      response burden, as measured by response rate, and questionnaire length. METHODS:
      A systematic literature review and meta-analysis of studies reporting response
      rates in relation to questionnaire length was performed. A Cochran-Mantel
      Haenszel test stratified by study using the Breslow-Day test was undertaken to
      investigate homogeneity of the odds ratios. RESULTS: Thirty-two reports were
      identified, of which 20 were eligible for inclusion in the meta-analysis. Three
      studies used patient input as main outcome when evaluating response burden. In
      the meta-analysis, a general association between response rate and questionnaire
      length was found (P <= 0.0001). Response rates were lower for longer
      questionnaires, but because the P value for test of homogeneity was P = 0.03,
      this association should be interpreted with caution because it is impossible to
      separate the impact of content from length of the questionnaires. CONCLUSION:
      Given the inherently problematic nature of comparing questionnaires of various
      lengths, it is preferable to base decisions on use of instruments on the content
      rather than the length per se.

PMID- 22152181
TI  - Development, reliability, and validity of a new Preference and Satisfaction
      Questionnaire.
AB  - OBJECTIVES: Existing questionnaires that assess preference and/or satisfaction
      with postmenopausal bone loss treatments were reviewed and determined to be
      inadequate for the assessment of an oral pill versus a subcutaneous injection.
      The Preference and Satisfaction Questionnaire (PSQ) was developed to assess
      preference, satisfaction, and bother with a weekly oral tablet versus a once
      every 6 months subcutaneous injection for treatment of postmenopausal bone loss.
      METHODS: Questions were developed based on literature review and expert input.
      Content validity of the PSQ in this patient population was assessed among current
      or previous bisphosphonate users in group interviews, and item comprehension and
      readability were also evaluated. Reliability, validity, and structure of the
      questionnaire were assessed in two phase 3 randomized clinical trials. RESULTS:
      Twenty-four women participated in cognitive interviews and found the PSQ
      understandable and acceptable. Subsequently, 1583 trial participants took the
      PSQ. Interitem correlations, ranging from 0.50 to 0.97 for preference items, 0.85
      to 0.94 for pill-satisfaction items, and 0.84 to 0.92 for injection-satisfaction
      items, and a well-fitting confirmatory factor analysis (root mean square error of
      approximation 0.04, nonnormed fit index 0.99, and root mean square residual 0.08)
      supported the structure of the instrument. Cronbach's alpha reliability values
      for pill satisfaction, injection satisfaction, pill bother, and injection bother
      were 0.93, 0.89, 0.82, and 0.61, respectively. Discriminative validity was
      indicated with better satisfaction and bother scores being related to adherence
      and the absence of adverse events. CONCLUSIONS: The PSQ is a valid and reliable
      measure and may be a valuable tool to assess patient preference and satisfaction
      with a weekly oral tablet and 6-month subcutaneous injection for postmenopausal
      bone loss.

PMID- 22152182
TI  - EQ-5D for the assessment of health-related quality of life and resource
      allocation in children: a systematic methodological review.
AB  - OBJECTIVES: EQ-5D is widely used in studies with adults as a source of generic
      health-related quality of life information and utility weights to inform resource
      allocation decisions. This methodological systematic review describes the extent
      to which EQ-5D has been used in the evaluation of children's health care,
      assesses psychometric properties, and makes recommendations for future good
      practice. METHODS: Systematic searches of databases and the Internet to identify
      studies published during 2000-2010 that either used EQ-5D with children younger
      than age 19 years as an outcome measure or reported psychometric data. Study
      characteristics, including measures and psychometric data, were extracted into
      tables for analysis. RESULTS: We identified 29 studies that used four versions of
      the EQ-5D: adult EQ-5D, EQ-5D-Y, Dutch EQ-5D child, and extended with cognitive
      dimension, EQ-5D+C. Twelve of 29 studies did not specify the EQ-5D version used.
      Existing literature lacks detail on the specific use of EQ-5D and its potential
      effects on findings. Version use and psychometric properties were inadequately
      reported. There are large gaps in current knowledge of psychometric properties
      across all versions when used with children. CONCLUSIONS: For reasons of
      comparability with resource use across adult and children's services, there are
      arguments for continued use of EQ-5D in studies with children. We recommend use
      of EQ-5D alongside children-specific quality of life measures and disease
      specific measures. Researchers are encouraged to undertake methodological and
      philosophical analyses to better understand and improve evidence as to how adults
      who make decisions about resource allocation can best take account of children in
      decision making.

PMID- 22152183
TI  - Effect of health-related quality-of-life instrument and quality-adjusted life
      year calculation method on the number of life years gained in the critical care
      setting.
AB  - OBJECTIVES: Health-related quality of life (HRQoL) and quality-adjusted life
      years (QALYs) gained are basic elements in the cost-utility evaluations of health
      care. Different HRQoL instruments produce different scores for the same patient,
      and thus also a different number of QALYs. We examined the effect of these
      factors on the number of QALYs gained and the cost per QALY in the critical care
      setting. METHODS: In 937 patients having been treated in the critical care
      setting in the Helsinki University Central Hospital the HRQoL scores were
      measured by the EQ-5D and 15D 6 and 12 months after start of treatment, and QALYs
      were calculated using four different sets of assumptions regarding recovery from
      disease. RESULTS: The mean number of QALYs gained during the first year after
      treatment ranged from 0.178 +/- 0.206 to 0.550 +/- 0.508 and the consequent cost
      per QALY from ?38,405 to ?118,668 depending on HRQoL instrument and assumptions
      used in the calculations regarding recovery from disease. CONCLUSIONS: The HRQoL
      instrument and the assumptions employed regarding recovery from disease have a
      great influence on the results of cost-utility analyses and should, therefore, be
      explicitly described in studies reporting QALYs. Furthermore, a common consensus
      on which calculation method should be used within critical care would be urgently
      needed.

PMID- 22152184
TI  - Social valuation of EQ-5D health states: the Chilean case.
AB  - BACKGROUND: Cost-effectiveness analysis has been recommended by many national
      agencies around the world as a valid methodology to improve resource allocation
      within the health-care system. If the preferences of the society are taken into
      account in such a decision-making process, it is generally recommended that these
      values should be elicited by using a generic health-related quality-of-life
      instrument, such as the EuroQol five-dimensional (EQ-5D) questionnaire.
      OBJECTIVES: To estimate a set of social values for EQ-5D questionnaire based on
      the time trade-off valuation technique for use in Chile. METHODS: A valuation
      questionnaire was applied to a probabilistic sample of 2000 individuals, aged 20
      years or older, living in the Metropolitan region. The fieldwork took place
      during October to November 2008. Utility weights for 42 health states were
      calculated directly by the application of time trade-off. Several random effect
      and ordinary least-squares regression models were fitted to these valuations to
      predict the full set of 243 health states generated by the EQ-5D system. The best
      model was chosen by applying criteria of parsimony, goodness of fit, and
      prediction capacity. RESULTS: The selected regression model was robust and showed
      better predictive characteristics than others reported in similar studies
      conducted elsewhere. The chosen regression model showed a R(2) of 0.34, mean
      absolute error of 0.017, and high predictive capacity. CONCLUSIONS: This study
      provides an EQ-5D social value set for domestic use in Chile. Our results differ
      from those reported in other countries, justifying the need to perform local
      studies that adequately reflect societal health preferences.

PMID- 22152185
TI  - Estimating population-based values for EQ-5D health states in Thailand.
AB  - OBJECTIVE: To derive EuroQol five-dimensional (EQ-5D) health states values from
      the Thai general population. METHODS: Forty-eight trained individuals
      successfully conducted interviews with a representative sample of 1409
      respondents in 2007. A total of 12 sets of health states were used with one set
      allocated to each respondent. A respondent was requested to assign values for 11
      states using the ranking and visual analogue scale methods and 10 states using
      the time trade-off method. The variables from the three existing models were used
      in model specifications and the best model was chosen on the basis of the extent
      of logical inconsistency in the estimated scores, predictive performance,
      parsimony, and sensitivity to changes in health. RESULTS: Eighty-six health
      states were valued. The mean age of respondents was 44.6 years old. The highly
      consistent respondents tend to give higher scores for mild states and lower
      scores for severe states, compared with those given by the highly inconsistent
      respondents. The best model used variables from the Dolan 1997 study and
      estimated from the scores given by the respondents with fewer than 11
      inconsistencies. The estimated scores are completely consistent, R(2) is 0.448.
      The second highest score was 0.766 given to state 11112 and the lowest score was 
      0.454 for state 33333. CONCLUSION: Values for EQ-5D health states were estimated
      from the Thai general population. This is the first Thai generic health state
      value results to be used in evaluating health interventions in Thailand.

PMID- 22152187
TI  - Elicitation of informed general population health state utility values: a review
      of the literature.
AB  - OBJECTIVE: Within a health-care decision-making context, whose health state
      utility values (HSUVs) should be used is constantly debated. This discussion is
      important because patient and general population utilities can differ. These
      discrepancies may be due to the general population not being informed about the
      health states. This article investigates approaches used to inform the general
      population about the health states that they are valuing. METHODS: Studies
      reporting methods to obtain informed general population HSUVs were identified,
      outlined, and critically appraised. RESULTS: Fourteen studies were identified:
      seven used information sessions, two used simulation methods, two used reflection
      and deliberation techniques, and three used adaptation exercises. CONCLUSIONS:
      This review demonstrated a range of approaches to elicit informed general
      population HSUVs. The majority of the studies indicated that informing the
      respondents significantly affected their opinions of the health states and hence
      their HSUVs. This suggests that the utilities that are currently used to guide
      health-care resource allocation decisions may not represent the general
      population's preferences for specific health states. This could result in
      decisions that do not maximize societal health benefits.

PMID- 22152186
TI  - Preferences for CT colonography and colonoscopy as diagnostic tests for
      colorectal cancer: a discrete choice experiment.
AB  - OBJECTIVE: Computed tomography colonography (CTC) is an alternative diagnostic
      test to colonoscopy for colorectal cancer and polyps. The aim of this study was
      to determine test characteristics important to patients and to examine trade-offs
      in attributes that patients are willing to accept in the context of the diagnosis
      of colorectal cancer. METHODS: A discrete choice study was used to assess
      preferences of patients with clinical indications suspicious of colorectal cancer
      who experienced both CTC and colonoscopy as part of a diagnostic accuracy study
      in South Australia. Results were analyzed by using a mixed logit model and
      presented as odds ratios (ORs) for preferring CTC over colonoscopy. RESULTS:
      Colonoscopy was preferred over CTC as the need for a second procedure after CTC
      increased (OR of preferring CTC to colonoscopy = 0.013), as the likelihood of
      missing cancers or polyps increased (OR of preferring CTC to colonoscopy = 0.62),
      and as CTC test cost increased (OR of preferring CTC to colonoscopy = 0.65-0.80).
      CTC would be preferred to colonoscopy if a minimal bowel preparation was
      available (OR = 1.7). Some patients were prepared to trade off the diagnostic and
      therapeutic advantage of colonoscopy for a CTC study with a less intensive bowel
      preparation. Preferences also varied significantly with sociodemographic
      characteristics. CONCLUSIONS: Despite CTC's often being perceived as a preferred
      test, this may not always be the case. Informed decision making for diagnostic
      tests for colorectal cancer should include discussion of the benefits, downsides,
      and uncertainties associated with alternative tests, as patients are willing and
      able to make trade-offs between what they perceive as the advantages and
      disadvantages of these diagnostic tests.

PMID- 22152188
TI  - The National Institute for Health and Clinical Excellence Single Technology
      Appraisal process: lessons from the first 4 years.
AB  - OBJECTIVES: The National Institute for Health and Clinical Excellence (NICE)
      Single Technology Appraisal (STA) process in the United Kingdom was established
      in 2005 in order to provide guidance on new technologies as close to their launch
      as possible. The NICE recommended timeframe for completion of an STA is 34 weeks.
      The purpose of this study was to map the first 95 STAs to collect information on
      a range of issues including timelines and appraisal decisions. METHODS: A mapping
      tool was devised to collect information from the NICE Web site. Data were
      analyzed by calculating frequencies. Simple descriptive statistics were applied
      where appropriate. RESULTS: Ninety-five STAs were included in the analysis.
      Almost one-third (30/95) initially identified topics did not go on to be
      appraised often due to licensing issues. Timelines were measured for 29 completed
      STAs. Eight (28%) of these were completed by 37 weeks and 20 (69%) by 42 weeks.
      When STAs with appeals were excluded, 31% (8/26) were completed by 37 weeks and
      85% (22/26) by 42 weeks. The incremental cost-effectiveness ratios reported by
      manufacturers were consistently lower than those estimated by the evidence review
      groups. In all, 76% (38/50) of the completed STAs resulted in an approval.
      CONCLUSIONS: The NICE Web site enabled access to almost all necessary
      information, although electronic documents were sometimes difficult to locate.
      One-third of the referred topics were suspended or terminated. The NICE STA
      process is slower than initially anticipated and this is primarily due to events
      outside of NICE's direct control.

PMID- 22152189
TI  - DRG-based hospital payment systems and technological innovation in 12 European
      countries.
AB  - OBJECTIVES: To assess how diagnosis-related group-based (DRG-based) hospital
      payment systems in 12 European countries participating in the EuroDRG project pay
      and incorporate technological innovation. METHODS: A standardized questionnaire
      was used to guide comprehensive DRG system descriptions. Researchers from each
      country reviewed relevant materials to complete the questionnaire and drafted
      standardized country reports. Two characteristics of DRG-based hospital payment
      systems were identified as particularly important: the existence of short-term
      payment instruments encouraging technological innovation in different countries,
      and the characteristics of long-term updating mechanisms that assure
      technological innovation is ultimately incorporated into DRG-based hospital
      payment systems. RESULTS: Short-term payment instruments and long-term updating
      mechanisms differ greatly among the 12 European countries included in this study.
      Some countries operate generous short-term payment instruments that provide
      additional payments to hospitals for making use of technological innovation
      (e.g., France). Other countries update their DRG-based hospital payment systems
      very frequently and use more recent data for updates. CONCLUSIONS: Generous short
      term payment instruments to promote technological innovation should be applied
      carefully as they may imply rapidly increasing health-care expenditures. In
      general, they should be granted only if rigorous analyses have demonstrated their
      benefits. If the evidence remains uncertain, coverage with evidence development
      frameworks or frequent updates of the DRG-based hospital systems may provide
      policy alternatives. Once the data and evidence base is substantially improved,
      future research should empirically investigate how different policy arrangements
      affect the adoption and use of technological innovation and health-care
      expenditures.

PMID- 22152190
TI  - Practical implications of differential discounting of costs and health effects in
      cost-effectiveness analysis.

PMID- 22152192
TI  - Defining epitope coverage requirements for T cell-based HIV vaccines: theoretical
      considerations and practical applications.
AB  - BACKGROUND: HIV vaccine development must address the genetic diversity and
      plasticity of the virus that permits the presentation of diverse genetic forms to
      the immune system and subsequent escape from immune pressure. Assessment of
      potential HIV strain coverage by candidate T cell-based vaccines (whether natural
      sequence or computationally optimized products) is now a critical component in
      interpreting candidate vaccine suitability. METHODS: We have utilized an N-mer
      identity algorithm to represent T cell epitopes and explore potential coverage of
      the global HIV pandemic using natural sequences derived from candidate HIV
      vaccines. Breadth (the number of T cell epitopes generated) and depth (the
      variant coverage within a T cell epitope) analyses have been incorporated into
      the model to explore vaccine coverage requirements in terms of the number of
      discrete T cell epitopes generated. RESULTS: We show that when multiple epitope
      generation by a vaccine product is considered a far more nuanced appraisal of the
      potential HIV strain coverage of the vaccine product emerges. By considering
      epitope breadth and depth several important observations were made: (1) epitope
      breadth requirements to reach particular levels of vaccine coverage, even for
      natural sequence-based vaccine products is not necessarily an intractable problem
      for the immune system; (2) increasing the valency (number of T cell epitope
      variants present) of vaccine products dramatically decreases the epitope
      requirements to reach particular coverage levels for any epidemic; (3)
      considering multiple-hit models (more than one exact epitope match with an
      incoming HIV strain) places a significantly higher requirement upon epitope
      breadth in order to reach a given level of coverage, to the point where low
      valency natural sequence based products would not practically be able to generate
      sufficient epitopes. CONCLUSIONS: When HIV vaccine sequences are compared against
      datasets of potential incoming viruses important metrics such as the minimum
      epitope count required to reach a desired level of coverage can be easily
      calculated. We propose that such analyses can be applied early in the planning
      stages and during the execution phase of a vaccine trial to explore theoretical
      and empirical suitability of a vaccine product to a particular epidemic setting.

PMID- 22152194
TI  - Effects of BRCA2 deficiency on telomere recombination in non-ALT and ALT cells.
AB  - BACKGROUND: Recent studies suggest that BRCA2 affects telomere maintenance.
      Interestingly, anti cancer treatments that involve BRCA2 and telomerase
      individually are currently being explored. In the light of the above recent
      studies their combinatorial targeting may be justified in the development of
      future treatments. In order to investigate effects of BRCA2 that can be explored
      for this combinatorial targeting we focused on the analysis of recombination
      rates at telomeres by monitoring T-SCEs (Telomere Sister Chromatid Exchanges).
      RESULTS: We observed a significant increase in T-SCE frequencies in four BRCA2
      defective human cell lines thus suggesting that BRCA2 suppresses recombination at
      telomeres. To test this hypothesis further we analyzed T-SCE frequencies in a set
      of Chinese hamster cell lines with or without functional BRCA2. Our results
      indicate that introduction of functional BRCA2 normalizes frequencies of T-SCEs
      thus supporting the notion that BRCA2 suppresses recombination at telomeres.
      Given that ALT (Alternative Lengthening of Telomeres) positive cells maintain
      telomeres by recombination we investigated the effect of BRCA2 depletion in these
      cells. Our results show that this depletion causes a dramatic reduction in T-SCE
      frequencies in ALT positive cells, but not in non-ALT cells. CONCLUSION: BRCA2
      suppresses recombination at telomeres in cells that maintain them by conventional
      mechanisms. Furthermore, BRCA2 depletion in ALT positive cells reduces high
      levels of T-SCEs normally found in these cells. Our results could be potentially
      important for refining telomerase-based anti-cancer therapies.

PMID- 22152196
TI  - Brief overview of United States involvement in global health training since World
      War II.

PMID- 22152195
TI  - Factors associated with misdiagnosis of smear-negative tuberculosis: an
      experience in Taiwan.
AB  - BACKGROUND: A negative sputum smear from a patient with history, physical
      examination, and chest x-ray findings suggestive of tuberculosis (TB) presents a
      diagnostic dilemma. We investigated the possible factors associated with a
      misdiagnosis and inappropriate treatment of TB among  such patients. METHODS: We
      reviewed the records of 193 patients whose diagnoses with TB included conflicting
      test results and were reported to the Taiwan Centers for Disease Control in 2004.
      When other conditions were found to underlie the initial abnormal chest x-ray
      finding, the diagnosis  was revised. RESULTS: Mycobacterium tuberculosis was
      isolated from sputum samples in 72 of 193 patients (37%), nontuberculous
      mycobacteria from 4 (2%), and no bacteriologic evidence of M. tuberculosis from
      117 (61%). The initial diagnosis of TB was revised for 26 (13.5%) patients. 
      Patients with positive M. tuberculosis culture had a lower incidence of revised
      diagnoses (4.2%, P < .001) than those negative for mycobacterial culture (17.1%)
      and those with nontuberculous mycobacteria (75%). Chest cavitations in this study
      were not a significant predictor  of revised diagnosis (odds ratio 0.30, P =
      .08). CONCLUSIONS: An incorrect diagnosis of TB despite a negative sputum smear
      result is more likely to be made for patients positive for nontuberculous
      mycobacteria culture and less likely for patients with positive M. tuberculosis 
      culture.

PMID- 22152203
TI  - Further evidence that propranolol is effective in the treatment of infantile
      hemagiomas.

PMID- 22152204
TI  - C reactive protein and procalcitonin are helpful in diagnosis of serious
      bacterial infections in children.

PMID- 22152193
TI  - Molecular signatures of peripheral blood mononuclear cells during chronic
      interferon-alpha treatment: relationship with depression and fatigue.
AB  - BACKGROUND: Interferon-alpha (IFN-alpha) treatment for infectious disease and
      cancer causes high rates of depression and fatigue, and has been used to
      investigate the impact of inflammatory cytokines on brain and behavior. However,
      little is known about the transcriptional impact of chronic IFN-alpha on immune
      cells in vivo and its relationship to IFN-alpha-induced behavioral changes.
      METHOD: Genome-wide transcriptional profiling was performed on peripheral blood
      mononuclear cells (PBMCs) from 21 patients with chronic hepatitis C virus (HCV)
      either awaiting IFN-alpha therapy (n=10) or at 12 weeks of IFN-alpha treatment
      (n=11). RESULTS: Significance analysis of microarray data identified 252 up
      regulated and 116 down-regulated gene transcripts. Of the up-regulated genes, 2'
      5'-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome
      (CFS), was the only gene that was differentially expressed in patients with IFN
      alpha-induced depression/fatigue, and correlated with depression and fatigue
      scores at 12 weeks (r=0.80, p=0.003 and r=0.70, p=0.017 respectively). Promoter
      based bioinformatic analyses linked IFN-alpha-related transcriptional alterations
      to transcription factors involved in myeloid differentiation, IFN-alpha
      signaling, activator protein-1 (AP1) and cAMP responsive element binding
      protein/activation transcription factor (CREB/ATF) pathways, which were derived
      primarily from monocytes and plasmacytoid dendritic cells. IFN-alpha-treated
      patients with high depression/fatigue scores demonstrated up-regulation of genes
      bearing promoter motifs for transcription factors involved in myeloid
      differentiation, IFN-alpha and AP1 signaling, and reduced prevalence of motifs
      for CREB/ATF, which has been implicated in major depression. CONCLUSIONS:
      Depression and fatigue during chronic IFN-alpha administration were associated
      with alterations in the expression (OAS2) and transcriptional control (CREB/ATF)
      of genes linked to behavioral disorders including CFS and major depression,
      further supporting an immune contribution to these diseases.

PMID- 22152205
TI  - Clinical features can help predict which infants with bronchiolitis will need
      hospital admission.

PMID- 22152206
TI  - History and physical exam findings help to identify children at low risk for
      pneumonia.

PMID- 22152207
TI  - Frenotomy improves breastfeeding immediately in neonates with ankyloglossia.

PMID- 22152208
TI  - Majority of children with chest pain do not have an underlying cardiac cause.

PMID- 22152216
TI  - Lack of effect of high-protein vs. high-carbohydrate meal intake on stress
      related mood and eating behavior.
AB  - BACKGROUND: Consumption of meals with different macronutrients, especially high
      in carbohydrates, may influence stress-related eating behavior. We aimed to
      investigate whether consumption of high-protein vs. high-carbohydrate meals
      influences stress-related mood, food reward, i.e. 'liking' and 'wanting', and
      post-meal energy intake. METHODS: Participants (n = 38, 19m/19f, age = 25 +/- 9
      y, BMI = 25.0 +/- 3.3 kg/m2) came to the university four times, fasted, once for
      a stress session receiving a high-protein meal, once for a rest session receiving
      a high-protein meal, once for a stress session receiving a high-carbohydrate meal
      and once for a rest session receiving a high-carbohydrate meal (randomized cross
      over design). The high-protein and high-carbohydrate test meals (energy
      percentage protein/carbohydrate/fat 65/5/30 vs. 6/64/30) matched for energy
      density (4 kJ/g) and daily energy requirements (30%). Stress was induced using an
      ego-threatening test. Pre- and post-meal 'liking' and 'wanting' (for bread,
      filling, drinks, dessert, snacks, stationery (non-food alternative as control))
      was measured by means of a computer test. Following the post-meal 'wanting'
      measurement, participants received and consumed their wanted food items (post
      meal energy intake). Appetite profile (visual analogue scales), mood state
      (Profile Of Mood State and State Trait Anxiety Inventory questionnaires), and
      post-meal energy intake were measured. RESULTS: Participants showed increased
      feelings of depression and anxiety during stress (P < 0.01). Consumption of the
      test meal decreased hunger, increased satiety, decreased 'liking' of bread and
      filling, and increased 'liking' of placebo and drinks (P < 0.0001). Food
      'wanting' decreased pre- to post-meal (P < 0.0001). The high-protein vs. high
      carbohydrate test meal induced lower subsequent 'wanting' and energy intake (1.7
      +/- 0.3 MJ vs. 2.5 +/- 0.4 MJ) only in individuals characterized by disinhibited
      eating behavior (factor 2 Three Factor Eating Questionnaire, n = 16), during rest
      (P <= 0.01). This reduction in 'wanting' and energy intake following the high
      protein meal disappeared during stress. CONCLUSIONS: Consumption of a high
      protein vs. high-carbohydrate meal appears to have limited impact on stress
      related eating behavior. Only participants with high disinhibition showed
      decreased subsequent 'wanting' and energy intake during rest; this effect
      disappeared under stress. Acute stress overruled effects of consumption of high
      protein foods. TRIAL REGISTRATION: The study was registered in the Dutch Trial
      Register (NTR1904). The protocol described here in this study deviates from the
      trial protocol approved by the Medical Ethical Committee of the Maastricht
      University as it comprises only a part of the approved trial protocol.

PMID- 22152217
TI  - Volume of the human septal forebrain region is a predictor of source memory
      accuracy.
AB  - Septal nuclei, components of basal forebrain, are strongly and reciprocally
      connected with hippocampus, and have been shown in animals to play a critical
      role in memory. In humans, the septal forebrain has received little attention. To
      examine the role of human septal forebrain in memory, we acquired high-resolution
      magnetic resonance imaging scans from 25 healthy subjects and calculated septal
      forebrain volume using recently developed probabilistic cytoarchitectonic maps.
      We indexed memory with the California Verbal Learning Test-II. Linear regression
      showed that bilateral septal forebrain volume was a significant positive
      predictor of recognition memory accuracy. More specifically, larger septal
      forebrain volume was associated with the ability to recall item source/context
      accuracy. Results indicate specific involvement of septal forebrain in human
      source memory, and recall the need for additional research into the role of
      septal nuclei in memory and other impairments associated with human diseases.

PMID- 22152219
TI  - First report of a gryporhynchid tapeworm (Cestoda: Cyclophyllidea) from New
      Zealand and from an eleotrid fish, described from metacestodes and in vitro-grown
      worms.
AB  - Metacestodes are often found in the body cavity of the common bully (Gobiomorphus
      cotidianus McDowall), from freshwater habitats in Otago, New Zealand.
      Identification of metacestodes relies only on the number, size and shape of the
      rostellar hooks. To attempt species determination, we cultivated metacestodes in
      vitro for up to 23 days, during which they matured to at least the male stage of
      development, although female organs were not discernable. Identified as members
      of the genus Paradilepis Hsu, 1935 (family Gryporhynchidae), these specimens are
      compared to previously described species, in particular P. minima (Goss, 1940),
      from Australia, the closest species, both geographically and morphologically.
      Although the size of scolex, suckers and proglottids differ significantly from
      those of P. minima, we are cautious about interpreting 'adults' grown in vitro,
      because we are unsure whether the artificial conditions alter development. For
      this reason, and because of the lack of female organs, we refrain from erecting a
      new species, and refer to the specimens as Paradilepis cf. minima until such time
      as the adults are found in the definitive host. With this proviso we present here
      a description of the in vitro-grown worms and the metacestodes as a preliminary
      study of this cestode. A molecular analysis of small subunit (SSU) rDNA
      sequences, shows the position of P. cf. minima and another gryporhynchid,
      Neogryporhynchus cheilancristrotus (Wedl, 1855), to be equivocal, but confirms
      their exclusion from the Dilepididae and Hymenolepididae. This is the first
      record of a gryporhynchid from New Zealand, and the first from the fish family
      Eleotridae.

PMID- 22152218
TI  - "It's almost expected": rural Australian Aboriginal women's reflections on
      smoking initiation and maintenance: a qualitative study.
AB  - BACKGROUND: Despite declining smoking rates among the general Australian
      population, rates among Indigenous Australians remain high, with 47% of the
      Indigenous population reporting daily smoking - twice that of other Australians.
      Among women, smoking rates are highest in younger age groups, with more than half
      of Aboriginal women smoking during pregnancy. A lack of research focused on
      understanding the social context of smoking by Aboriginal women in rural
      Australia limits our ability to reduce these rates. This study aimed to explore
      the factors contributing to smoking initiation among rural Aboriginal women and
      girls and the social context within which smoking behaviour occurs. METHODS: We
      conducted three focus groups with 14 Aboriginal women and service providers and
      22 individual interviews with Aboriginal women from four rural communities to
      explore their perceptions of the factors contributing to smoking initiation among
      Aboriginal girls. RESULTS: Four inter-related factors were considered important
      to understanding the social context in which girls start smoking: colonisation
      and the introduction of tobacco; normalization of smoking within separate
      Aboriginal social networks; disadvantage and stressful lives; and the importance
      of maintaining relationships within extended family and community networks.
      Within this context, young girls use smoking to attain status and as a way of
      asserting Aboriginal identity and group membership, a way of belonging, not of
      rebelling. Family and social structures were seen as providing strong support,
      but limited the capacity of parents to influence children not to smoke.
      Marginalization was perceived to contribute to limited aspirations and
      opportunities, leading to pleasure-seeking in the present rather than having
      goals for the future. CONCLUSIONS: The results support the importance of
      addressing contextual factors in any strategies aimed at preventing smoking
      initiation or supporting cessation among Aboriginal girls and women. It is
      critical to acknowledge Aboriginal identity and culture as a source of
      empowerment; and to recognise the role of persistent marginalization in
      contributing to the high prevalence and initiation of smoking.

PMID- 22152220
TI  - Effect of age on fatty infiltration of supraspinatus muscle after experimental
      tendon release in rats.
AB  - BACKGROUND: Rotator cuff tendon tear is a leading cause for atrophy, fibrosis and
      fatty infiltration of the rotator cuff muscles. The pathophysiology of fatty
      muscle infiltration is not well understood. An animal model suited to study
      cellular and molecular mechanisms would therefore be desirable. While a rat model
      has been established for chronic rotator cuff tendon pathology, sufficient and
      easily identifiable fatty infiltration of the muscle has not yet been shown in
      rats. As younger animals regenerate better, we hypothesized that the absence of a
      sufficient amount of fatty infiltration in previous experiments was due to the
      selection of young animals and that older animals would exhibit higher amounts of
      fatty infiltration after tendon tear. FINDINGS: The supraspinatus tendon was
      released using tenotomy in 3 young (6 weeks old) and in 3 aged (24 months old)
      Sprague Dawley rats (group I and II). Another 3 aged (24 months old) rats
      underwent sham surgery and served as a control group (group III). In group I and
      II retraction of the musculotendinous unit was allowed for 6 weeks. All animals
      were sacrificed 6 weeks after surgery and the supraspinatus muscles were
      harvested. Each sample was examined for fatty infiltration of the muscle by
      histological methods and micro-CT. In histology, fat cells were counted with a 10
      fold magnification in 6 fields of view twice. An adjusted measurement setup was
      developed for the use of micro-CT to quantify the absorption coefficient of the
      muscle as a reciprocal indicator for fatty infiltration, based on the established
      procedure for quantification of fatty infiltration on CT in humans.Tenotomy
      resulted in an insignificant increase of fat cells in histological sections in
      both, aged and young rats. Micro-CT was able to quantify small differences in the
      absorption coefficients of muscle samples; the absorption coefficient was 8.1% +/
      11.3% lower in retracted muscles (group I and II) compared with the control
      (group III), indicating a tendency towards a higher amount of intra- and/or
      extracellular fat. Absorption was 4.28% +/- 3.2% higher in aged compared with
      young muscles; however, this difference could not be confirmed by histology.
      CONCLUSIONS: Substantial fatty muscle infiltration following chronic retraction
      after supraspinatus tenotomy could be documented histologically neither in young
      nor aged rats. Although micro-CT was able to reveal minor differences in
      absorption between the studied groups, the differences were too small to make the
      rat supraspinatus model interesting to study fatty infiltration of the
      chronically retracted muscle.

PMID- 22152221
TI  - Increased circulating leukocyte numbers and altered macrophage phenotype
      correlate with the altered immune response to brain injury in metallothionein
      (MT)-I/II null mutant mice.
AB  - BACKGROUND: Metallothionein-I and -II (MT-I/II) is produced by reactive
      astrocytes in the injured brain and has been shown to have neuroprotective
      effects. The neuroprotective effects of MT-I/II can be replicated in vitro which
      suggests that MT-I/II may act directly on injured neurons. However, MT-I/II is
      also known to modulate the immune system and inflammatory processes mediated by
      the immune system can exacerbate brain injury. The present study tests the
      hypothesis that MT-I/II may have an indirect neuroprotective action via
      modulation of the immune system. METHODS: Wild type and MT-I/II(-/-) mice were
      administered cryolesion brain injury and the progression of brain injury was
      compared by immunohistochemistry and quantitative reverse-transcriptase PCR. The
      levels of circulating leukocytes in the two strains were compared by flow
      cytometry and plasma cytokines were assayed by immunoassay. RESULTS: Comparison
      of MT-I/II(-/-) mice with wild type controls following cryolesion brain injury
      revealed that the MT-I/II(-/-) mice only showed increased rates of neuron death
      after 7 days post-injury (DPI). This coincided with increases in numbers of T
      cells in the injury site, increased IL-2 levels in plasma and increased
      circulating leukocyte numbers in MT-I/II(-/-) mice which were only significant at
      7 DPI relative to wild type mice. Examination of mRNA for the marker of
      alternatively activated macrophages, Ym1, revealed a decreased expression level
      in circulating monocytes and brain of MT-I/II(-/-) mice that was independent of
      brain injury. CONCLUSIONS: These results contribute to the evidence that MT-I/II(
      /-) mice have altered immune system function and provide a new hypothesis that
      this alteration is partly responsible for the differences observed in MT-I/II(-/
      ) mice after brain injury relative to wild type mice.

PMID- 22152222
TI  - Type of diet modulates the metabolic response to sleep deprivation in rats.
AB  - BACKGROUND: Evidence suggests that sleep loss is associated with an increased
      risk of obesity and diabetes; however, animal models have failed to produce
      weight gain under sleep deprivation (SD). Previous studies have suggested that
      this discrepancy could be due to more extreme SD conditions in experimental
      animals, their higher resting metabolic rate than that of humans, and the
      decreased opportunity for animals to ingest high-calorie foods. Thus, our
      objective was to determine whether diets with different textures/compositions
      could modify feeding behavior and affect the metabolic repercussions in SD in
      rats. METHODS: Three groups of male rats were used: one was designated as
      control, one was sleep deprived for 96 h by the platform technique (SD-96h) and
      one was SD-96h followed by a 24-h recovery (rebound). In the first experiment,
      the animals were fed chow pellets (CPs); in the second, they received high-fat
      diet and in the third, they were fed a liquid diet (LD). RESULTS: We observed
      that SD induces energy deficits that were related to changes in feeding behavior
      and affected by the type of diet consumed. Regardless of the diet consumed, SD
      consistently increased animals' glucagon levels and decreased their leptin and
      triacylglycerol levels and liver glycogen stores. However, such changes were
      mostly avoided in the rats on the liquid diet. SD induces a wide range of
      metabolic and hormonal changes that are strongly linked to the severity of weight
      loss. CONCLUSIONS: The LD, but not the CP or high-fat diets, favored energy
      intake, consequently lessening the energy deficit induced by SD.

PMID- 22152223
TI  - Core competencies in the science and practice of knowledge translation:
      description of a Canadian strategic training initiative.
AB  - BACKGROUND: Globally, healthcare systems are attempting to optimize quality of
      care. This challenge has resulted in the development of implementation science or
      knowledge translation (KT) and the resulting need to build capacity in both the
      science and practice of KT. FINDINGS: We are attempting to meet these challenges
      through the creation of a national training initiative in KT. We have identified
      core competencies in this field and have developed a series of educational
      courses and materials for three training streams. We report the outline for this
      approach and the progress to date. CONCLUSIONS: We have prepared a strategy to
      develop, implement, and evaluate a national training initiative to build capacity
      in the science and practice of KT. Ultimately through this initiative, we hope to
      meet the capacity demand for KT researchers and practitioners in Canada that will
      lead to improved care and a strengthened healthcare system.

PMID- 22152224
TI  - Healthcare policy tools as determinants of health-system efficiency: evidence
      from the OECD.
AB  - This paper assesses which policy-relevant characteristics of a healthcare system
      contribute to health-system efficiency. Health-system efficiency is measured
      using the stochastic frontier approach. Characteristics of the health system are
      included as determinants of efficiency. Data from 21 OECD countries from 1970 to
      2008 are analysed. Results indicate that broader health-system structures, such
      as Beveridgian or Bismarckian financing arrangements or gatekeeping, are not
      significant determinants of efficiency. Significant contributors to efficiency
      are policy instruments that directly target patient behaviours, such as insurance
      coverage and cost sharing, and those that directly target physician behaviours,
      such as physician payment methods. From the perspective of the policymaker,
      changes in cost-sharing arrangements or physician remuneration are politically
      easier to implement than changes to the foundational financing structure of the
      system.

PMID- 22152225
TI  - Cytokine research in Belgium.

PMID- 22152226
TI  - Biology and signal transduction pathways of the Lymphotoxin-alphabeta/LTbetaR
      system.
AB  - This review focuses on the biological functions and signalling pathways activated
      by Lymphotoxin alpha (LTalpha)/Lymphotoxin beta (LTbeta) and their receptor
      LTbetaR. Genetic mouse models shed light on crucial roles for LT/LTbetaR to build
      and to maintain the architecture of lymphoid organs and to ensure an adapted
      immune response against invading pathogens. However, chronic inflammation,
      autoimmunity, cell death or cancer development are disorders that occur when the
      LT/LTbetaR system is twisted. Biological inhibitors, such as antagonist
      antibodies or decoy receptors, have been developed and used in clinical trials
      for diseases associated to the LT/LTbetaR system. Recent progress in the
      understanding of cellular trafficking and NF-kappaB signalling pathways
      downstream of LTalpha/LTbeta may bring new opportunities to develop therapeutics
      that target the pathological functions of these cytokines.

PMID- 22152227
TI  - Complications of nephrogenic systemic fibrosis following repeated exposure to
      gadolinium in a man with hypothyroidism: a case report.
AB  - INTRODUCTION: Nephrogenic systemic fibrosis is a condition that has recently been
      recognized in patients with chronic renal disease and is associated with use of
      gadolinium-based contrast agents of ubiquitous use in magnetic resonance imaging
      scans. The condition is believed to arise through inadequate renal clearance of
      the gadolinium-based contrast agents, resulting in bodily deposition of the
      gadolinium; this is most widely recognized in the skin, but also occurs in other
      tissues. CASE PRESENTATION: We report the case of a 52-year-old Caucasian man
      with hypothyroidism and chronic renal disease who developed nephrogenic systemic
      fibrosis upon repeated exposure to gadolinium, and who presented with a
      subsequent malabsorption of levothyroxine. This malabsorption resolved only
      partially upon amelioration of other conditions that might contribute to
      malabsorption, including edema and infectious diarrhea. The presence of
      gadolinium was quantified in specimens from his gastrointestinal tract. Our
      patient otherwise demonstrated adequate gastrointestinal nutritive absorption,
      objectively shown by normal albumin levels, resolution of diarrhea, and
      maintenance of his bodily weight. CONCLUSIONS: Our observations suggest that
      nephrogenic systemic fibrosis can also affect tissue of the gastrointestinal
      tract, potentially contributing to partial malabsorption of levothyroxine in
      patients with hypothyroidism.

PMID- 22152228
TI  - Baseline characteristics and hospital mortality in the Acute Heart Failure
      Database (AHEAD) Main registry.
AB  - INTRODUCTION: The prognosis of patients hospitalized with acute heart failure
      (AHF) is poor and risk stratification may help clinicians guide care. The
      objectives of the Acute Heart Failure Database (AHEAD) registry are to assess
      patient characteristics, etiology, treatment and outcome of AHF. METHODS: The
      AHEAD main registry includes patients hospitalized for AHF in seven centers with
      a Catheterization Laboratory Service in the Czech Republic. The data were
      collected from September 2006 to October 2009. The inclusion criteria for the
      database adhere to the European guidelines for AHF (2005) and patients were
      systematically classified according to the basic syndromes, type and etiology of
      AHF. RESULTS: Of 4,153 patients, 12.7% died during hospitalization. The median
      length of hospitalization was 7.1 days. Mean age of patients was 71.5 +/- 12.4
      years; men were younger (68.6 +/- 12.4 years) compared to women (75.5 +/- 11.5
      years) (P < 0.001). De-novo heart failure was seen in 58.3% of the patients.
      According to the classification of heart failure syndromes, acute decompensated
      heart failure (ADHF) was reported in 55.3%, hypertensive AHF in 4.4%, pulmonary
      edema in 18.4%, cardiogenic shock in 14.7%, high output failure in 3.3%, and
      right heart failure in 3.8%. The mortality of cardiogenic shock was 62.7%, of
      right AHF 16.7%, of pulmonary edema 7.1%, of high output HF 6.1%, whereas the
      mortality of hypertensive AHF or ADHF was < 2.5%. According to multivariate
      analyses, low systolic blood pressure, low cholesterol level, hyponatremia,
      hyperkalemia, the use of inotropic agents and norepinephrine were predictive
      parameters for in-hospital mortality in patients without cardiogenic shock.
      Severe left ventricular dysfunction and renal insufficiency were predictive
      parameters for mortality in patients with cardiogenic shock. Invasive ventilation
      and age over 70 years were the most important predictive factors for mortality in
      both genders with or without cardiogenic shock. CONCLUSIONS: The AHEAD Main
      registry provides up-to-date information on the etiology, treatment and hospital
      outcomes of patients hospitalized with AHF. The results highlight the highest
      risk patients.

PMID- 22152229
TI  - The relative impact of vision impairment and cardiovascular disease on quality of
      life: the example of pseudoxanthoma elasticum.
AB  - OBJECTIVE: To investigate the impact of pseudoxanthoma elasticum (PXE), a rare
      hereditary disease of concurrent vision impairment (VI) and cardiovascular
      complications (CVCs), on vision-related (VRQoL) and health-related quality of
      life (HRQoL). METHODS: VRQoL and HRQoL were assessed using the Impact of Vision
      Impairment (IVI) questionnaire and the Short Form Health Survey (SF-36) in 107
      PXE patients. Patients were stratified into four groups: A = no VI or CVC; B =
      CVCs only; C = VI only; and D = both VI and CVCs. RESULTS: Following Rasch
      analysis, the IVI was found to function as a vision-specific functioning and
      emotional well-being subscale, and the SF-36 as a health-related physical
      functioning and mental health subscale. The presence of VI and CVC were
      significant predictors of vision-specific functioning and emotional well-being (p
      < 0.001), with a clinically meaningful decrement in vision-specific functioning
      in patients with VI. No associations were found for the SF-36 Physical
      Functioning and Mental Health scores between any groups. CONCLUSIONS: Vision
      impaired patients with PXE report significantly poorer vision-specific
      functioning than PXE patients without VI. In contrast, the relative impact of PXE
      on reported general HRQoL was much less. Our results suggest that vision
      impairment has the larger impact on QoL in this sample.

PMID- 22152230
TI  - Incremental benefits and cost of coordinated anxiety learning and management for
      anxiety treatment in primary care.
AB  - BACKGROUND: Improving the quality of mental health care requires integrating
      successful research interventions into 'real-world' practice settings.
      Coordinated Anxiety Learning and Management (CALM) is a treatment-delivery model
      for anxiety disorders encountered in primary care. CALM offers cognitive
      behavioral therapy (CBT), medication, or both; non-expert care managers assisting
      primary care clinicians with adherence promotion and medication optimization;
      computer-assisted CBT delivery; and outcome monitoring. This study describes
      incremental benefits, costs and net benefits of CALM versus usual care (UC).
      METHOD: The CALM randomized, controlled effectiveness trial was conducted in 17
      primary care clinics in four US cities from 2006 to 2009. Of 1062 eligible
      patients, 1004 English- or Spanish-speaking patients aged 18-75 years with panic
      disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD)
      and/or post-traumatic stress disorder (PTSD) with or without major depression
      were randomized. Anxiety-free days (AFDs), quality-adjusted life years (QALYs)
      and expenditures for out-patient visits, emergency room (ER) visits, in-patient
      stays and psychiatric medications were estimated based on blinded telephone
      assessments at baseline, 6, 12 and 18 months. RESULTS: Over 18 months, CALM
      participants, on average, experienced 57.1 more AFDs [95% confidence interval
      (CI) 31-83] and $245 additional medical expenses (95% CI $-733 to $1223). The
      mean incremental net benefit (INB) of CALM versus UC was positive when an AFD was
      valued >=$4. For QALYs based on the Short-Form Health Survey-12 (SF-12) and the
      EuroQol EQ-5D, the mean INB was positive at >=$5000. CONCLUSIONS: Compared with
      UC, CALM provides significant benefits with modest increases in health-care
      expenditures.

PMID- 22152232
TI  - [Role of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of
      portal hypertension complications].

PMID- 22152233
TI  - [Transjugular intrahepatic portosystemic shunt: some related medical problems].

PMID- 22152234
TI  - [Transjugular intrahepatic portosystemic shunt: indications and current status].

PMID- 22152235
TI  - [Transjugular intrahepatic portosystemic shunt: contraindications and
      complications].

PMID- 22152236
TI  - [Standardization of transjugular intrahepatic portosystemic shunt].

PMID- 22152231
TI  - Strategies and methods to study sex differences in cardiovascular structure and
      function: a guide for basic scientists.
AB  - BACKGROUND: Cardiovascular disease remains the primary cause of death worldwide.
      In the US, deaths due to cardiovascular disease for women exceed those of men.
      While cultural and psychosocial factors such as education, economic status,
      marital status and access to healthcare contribute to sex differences in adverse
      outcomes, physiological and molecular bases of differences between women and men
      that contribute to development of cardiovascular disease and response to therapy
      remain underexplored. METHODS: This article describes concepts, methods and
      procedures to assist in the design of animal and tissue/cell based studies of sex
      differences in cardiovascular structure, function and models of disease. RESULTS:
      To address knowledge gaps, study designs must incorporate appropriate
      experimental material including species/strain characteristics, sex and hormonal
      status. Determining whether a sex difference exists in a trait must take into
      account the reproductive status and history of the animal including those used
      for tissue (cell) harvest, such as the presence of gonadal steroids at the time
      of testing, during development or number of pregnancies. When selecting the type
      of experimental animal, additional consideration should be given to diet
      requirements (soy or plant based influencing consumption of phytoestrogen),
      lifespan, frequency of estrous cycle in females, and ability to investigate
      developmental or environmental components of disease modulation. Stress imposed
      by disruption of sleep/wake cycles, patterns of social interaction (or degree of
      social isolation), or handling may influence adrenal hormones that interact with
      pathways activated by the sex steroid hormones. Care must be given to selection
      of hormonal treatment and route of administration. CONCLUSIONS: Accounting for
      sex in the design and interpretation of studies including pharmacological effects
      of drugs is essential to increase the foundation of basic knowledge upon which to
      build translational approaches to prevent, diagnose and treat cardiovascular
      diseases in humans.

PMID- 22152237
TI  - [Clinical application of the transjugular intrahepatic portosystemic stent-shunt
      in the emergency treatment of esophagogastric varices bleeding due to cirrhosis].
AB  - OBJECTIVE: To investigate the effects of transjugular intrahepatic portosystemic
      stent-shunt (TIPS) in emergency treatment of esophagogastric varices bleeding for
      the cirrhosis patients. METHODS: 39 cases with esophageal and gastric varices
      bleeding due to liver cirrhosis received TIPS and were followed-up for 1 to 12
      months, the short-term effects including 24 hours haemostasis rates post TIPS,
      pressure gradient between portal vein and systemic circulation, average pressure
      of portal vein were observed. The levels of albumin, cholinesterase, total
      bilirubin and prothrombin time post TIPS were also evaluated were observed and
      evaluated. RESULTS: 37 cases received TIPS successfully among the 39 patients,
      with a total effective rate of 94.87% (37/39) and the rate of hemostasis in 24
      hours was 100%. PSG dropped from (30.44+/-7.68) cm H2O to (18.78+/-4.71) cm H2O,
      mean portal pressure declined from (38.22+/-7.40) cm H2O to (27.00+/-5.38) cm H2O
      (P is less than 0.01). No significant differences existed at the level of
      albumin(A) and cholinesterase (CHE) before and after operation (P is more than
      0.05). The relapse rate of frame stenosis was 5.71% (2/35). The incidence rate of
      hepatic encephalopathy was 13.51% (5/37). The relapse rate of rehaemorrhagia was
      2.86% (1/35). The incidence rate of hepatic failure was 2.70% (1/37). The death
      rate was 5.71% (2/35). CONCLUSION: The effect of TIPS in treating portal
      hypertension caused by liver cirrhosis is prominent and safe, and is worthy of
      clinical application.

PMID- 22152238
TI  - [Prevention of variceal rebleeding by TIPS combined with embolization of gastric
      coronary veins: a clinical controlled study].
AB  - OBJECTIVE: To prospectively compare the rates of gastroesophageal variceal
      rebleeding in patients underwent TIPS alone and TIPS combined with embolization
      of gastric coronary veins. METHODS: According to the bleeding state within one
      week before the shunt placement, 122 patients with hepatic cirrhosis indicated
      for the secondary prevention of gastroesophageal variceal rebleeding were
      allocated to the shunt group (n = 44, treated with TIPS alone) and the shunt plus
      embolization group (n = 78, treated with TIPS combined with embolization of
      gastric coronary veins). All the patients were followed up for 1 year, and the 1
      year cumulative rates of rebleeding, shunt patency and mortality were compared.
      RESULTS: The basic characteristics of patients in the two groups were comparable
      (P is more than 0.05). The 1-year cumulative re-bleeding rates were 41.5% in the
      shunt group and 19.5% in the shunt combined with embolization group (x2 = 6.320,
      P = 0.012). The differences of 1-year cumulative rates of shunt patency and
      mortality between the two groups were not significant (P is more than 0.05).
      CONCLUSIONS: TIPS combined with embolization of gastric coronary veins could
      reduce significantly the rate of rebleeding in 1 year after the shunt placement
      as compared with TIPS alone.

PMID- 22152239
TI  - [Early hepatic encephalopathy after transjugular intrahepatic portosystemic
      shunt: the risk factors and long-time survival].
AB  - OBJECTIVE: To identify the risk factors of early post-TIPS hepatic encephalopathy
      (HE) and the long-time survival of patients with or without early post-TIPS HE.
      METHODS: Consecutive cirrhotic patients who underwent TIPS for variceal
      rebleeding or refractory ascites in our center from January 2003 to December 2008
      were included in this study. More than 60 clinical characteristics were enrolled
      in univariate analysis and logistic regression analysis to define the risk
      factors of HE in 3 months after TIPS procedure (early post-TIPS HE). The long
      time survival of patients with or without early post-TIPS HE was compared by Cox
      regression with several covariates. RESULTS: According to our inclusion criteria,
      190 patients were included. The median follow-up was 30.5 months. Lower serum
      concentration of fibrinogen and higher Child-Pugh score were the independent risk
      factors for suffering early post-TIPS HE. Patients without early post-TIPS HE
      after TIPS showed better prognosis than those with early post-TIPS HE after TIPS
      (P = 0.044). CONCLUSION: Patients with lower serum fibrinogen and higher Child
      Pugh score before TIPS might be more probably attacked by early post-TIPS HE
      which indicated worse long-term survival.

PMID- 22152240
TI  - [The velocity of HCV subtype 6a transmission in southwest China].
AB  - OBJECTIVE: To estimate the velocity of HCV subtype 6a transmission in Southwest
      China. METHODS: The HCV CE1 region from 61 patients infected with HCV genotype 6
      were amplificated by RT-PCR and sequenced. The subtypes were identified, and the
      period of HCV 6a strains originated in southwest china was estimated by using
      molecular clock phylogenetic analysis. The velocity of HCV subtype 6a
      transmission in southwest China was estimated by BEAST v1.6.1 and Tracer v1.5
      software theoretically. RESULTS: Most of HCV 6a strains distributed in Southwest
      China origine around the year 1968 and at last 4 epidemic strains existed. The
      earlier origine strains could be isolated both in intravenous drug users (IDU)
      and non-IDU patients. After 1997, the HCV 6a strains transmission in southwest
      China accelerated and the trend intensified in 2007. CONCLUSION: HCV 6a strains
      spread fastly both in IDU and non-IDU patients, which might be the main HCV
      subtype distributed in Southwest China in the future.

PMID- 22152241
TI  - [Characterization of HBsAbs in occult hepatitis B virus infection].
AB  - OBJECTIVE: To investigate the properties of HBsAb in occult hepatitis B virus
      infection and its affinity to different serotypes of hepatitis B virus surface
      antigen (HBsAg). METHODS: Long-term follow-up was conducted in 2 HBsAb positive
      patients with occult hepatitis B virus infection. HBsAg was detected using
      multiple diagnostic kits and the HBsAb subtype was determined by performing
      neutralization experiments with different serotypes of HBsAg. The viral S gene
      was PCR-amplified and mutation analysis was conducted. Plasmids expressing HBsAgs
      were constructed by inserting these PCR products into an eukaryotic expression
      vector and were then transfected into HepG2 cells. The cell culture supernatant
      and cellular extracts were detected for HBsAg respectively. Neutralization
      experiments were carried out in the cell culture supernatant from HBsAg plasmids
      transfected HepG2 cells and serum samples from these patients and others who had
      been confirmed to be positive for HBsAb. RESULTS: Multiple tests using various
      diagnostic kits showed that the 2 patients were negative for HBsAg and the three
      different serotypes of HBsAg (adr, adw, ay) could neutralize 82.1%-100% of HBsAb
      existed in the 2 patients. Sequence analysis of S gene cloned from these patients
      revealed that the homology to reference strain were 95.13%-97.79% and 92.04%
      95.58% respectively at the nucleotide and amino acid levels. Quantitation of
      HBsAg showed that the expression levels of HBsAg from the two patients were 41.1%
      and 22.6% respectively of that of control HBsAg in cell culture supernatant and
      48.1% and 59.3% respectively in cellular extract, and the supernatant/cell lysate
      ratios were 0.85 and 0.38 respectively. In neutralization experiments, HBsAg
      could be totally absorbed by control serum, whereas could only be partially
      neutralized by HBsAbs from the two patients (F = 353.6 and 645.2, P is less than
      0.01). CONCLUSION: Both the antigenicity and the ability of HBsAg secreted
      outside of the cells are decreased in these HBsAb-positive patients with occult
      HBV infection. The HBsAbs are mainly specific for common epitopes among different
      serotypes of HBsAg and are probably different as compared with those produced by
      vaccine inoculation.

PMID- 22152242
TI  - [Expression of COX-2 and PPARg in the livers of patients with acute on chronic
      HBV-related liver failure and their relationship with clinic parameters].
AB  - OBJECTIVE: To study the expressions of cyclooxygenase-2 (COX-2) and Peroxisome
      proliferator-activated receptor gamma (PPARg) in liver of patients with hepatitis
      B virus (HBV) related acute-on-chronic liver failure (ACLF) and their correlation
      with clinical parameters. METHODS: 35 patients with ACLF, 35 patients with HBV
      related chronic liver failure (CLF), 27 patients with chronic hepatitis B(CHB)
      and 15 normal control were enrolled to study the expressions of COX-2 and PPARg
      in the liver tissues by immunohistochemical staining, and to analyze the
      correlation of the COX-2 and PPARg levels in liver tissues with clinical
      parameters. RESULTS: COX-2 was distinctly expressed in the cytoplasm of the
      hepatocytes, but PPARg was mostly expressed in the nuclei of the hepatocytes and
      also could be seen in the cytoplasm. The expressions of COX-2 in the liver of
      ACLF, CLF and CHB groups increased significantly as compared with NC group (z = 
      5.18, -4.50, -5.32, P is less than 0.01). The levels of COX-2 in ACLF livers also
      increased evidently as compared with CLF groups (z = -1.98, P is less than 0.05).
      The expression levels of PPARg in ACLF liver tissues were much higher than the
      other three groups, and statistical significances existed between ACLF group and
      the other two groups (CLF, NC groups) (z = -2.62, -4.28, P is less than 0.01). In
      ACLF group, the expression of COX-2 correlated with MELD score (r = 0.337, P is
      less than 0.05) and the expression of PPARg correlated with HBV DNA load (r =
      0.348, P is less than 0.05). Clinical data showed that the levels of AST, TBil,
      CHOL, PT, INR, FIB and MELD score in ACLF group were significantly different from
      that in CLF, CHB and NC groups. CONCLUSIONS: COX-2 expressed in liver may be a
      marker to reflect the degree of inflammation and injury of liver tissue. The
      PPARg expression of liver could be increased during chronic HBV infection and may
      be a protective mechanism against liver injury.

PMID- 22152243
TI  - [Evolution of hepatitis B virus quasispecies during antiviral therapy in one
      chronic hepatitis B patient].
AB  - OBJECTIVE: To investigate the evolution of hepatitis B virus (HBV) quasispecies
      in one patient during lamivudine (LAM) monotherapy and switching to entecavir
      (ETV) rescue treatment. METHODS: Serum samples were taken at seven different time
      points during antiviral therapy (0, 24, 48, 60, 72, 96, 152 weeks, respectively),
      the HBV DNA polymerase gene was amplified, cloned and sequenced to analyze the
      amino acid substitutions within HBV DNA polymerase gene and distribution of virus
      quasispecies. Quantitative detection of the HBV wild strains and total virus was
      performed by amplification refractory mutation system real-time PCR (ARMS-PCR).
      RESULTS: Three mutation patterns detected during antiviral therapy in the
      patient: rtM204V, rtM204V+rtL180M and rtM204I. The HBV quasispecies were found
      always in dynamic variation. The HBV populations were completely replaced with
      the LAM-resistant variants when the viral breakthrough was encountered during LAM
      monotherapy. Interestingly, the wild-type variants presented gradually dominant
      (79.3%) with the decline of HBV DNA load after switching to ETV rescue
      administration. ARMS-PCR results showed that the wild-type variants account ed
      for 68.55% of the HBV populations at baseline and this proportion declined to
      0.21% when the viral breakthrough emerged under LAM therapy. The wild-type
      variants gradually increased from week 24 after switching to ETV rescue therapy
      and the proportion of HBV wild-type variants in the population fluctuated between
      16.01% to 26.93%. CONCLUSIONS: The distribution of virus quasispecies were always
      in dynamic variation during sequential therapy with nucleotide analogs in chronic
      hepatitis B patients. Different patterns of dynamic HBV quasispecies may have
      different contribution in ETV resistance in LMV refractory patients with ETV
      administration.

PMID- 22152244
TI  - [Peroxisome proliferator activated receptor gamma activation and overexpression
      prevent hepatocellular apoptosis of nutritional fibrotic steatohepatitis in
      mice].
AB  - OBJECTIVE: To elucidate the effect of targeted gene modulation of peroxisome
      proliferator activated receptor gamma (PPARg) on hepatocellular apoptosis in
      nutritional fibrotic steatohepatitis in mice. C57BL/6J mice were fed with high
      fat, methionine-choline deficient (MCD) diet for 8 weeks to induce fibrotic
      steatohepatitis. Mice fed the MCD diet were treated with adenovirus carrying
      PPARg (Ad-PPARg), adenovirus-beta-galactosidase (Ad-LacZ), Ad-PPARg plus PPARg
      agonist rosiglitazone, or PPARg antagonist 2-chloro-5-nitro- benzanilide
      (GW9662), respectively. H and E stain was performed for observation of
      hepatocellular apoptosis, hepatic steatosis, inflammation and fibrosis in the
      liver sections. The expression levels of mRNA and protein of PPARg and apoptosis
      related genes, Fas, Fas Ligand (FasL), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2
      associated X protein (Bax) and cysteine-containing aspartate-specific proteases-3
      (caspase-3) were detected by real-time RT-PCR and Western blot assay,
      respectively. RESULTS: Mice fed with MCD diet for 8 weeks showed severe hepatic
      injury including steatosis, hepatocellular apoptosis, inflammatory infiltration
      and fibrosis, concomitancy with enhanced expression of pro-apoptosis genes, Fas,
      FasL, Bax and caspase-3 and increased expression of anti-apoptosis gene Bcl-2, by
      comparing with the control group. The mRNA expression levels of these genes were
      3.59+/-0.35 vs 1.11+/-0.37, 4.37+/-1.03 vs 1.09+/-0.33, 4.27+/-0.48 vs 1.03+/
      0.10, 4.93+/-0.67 vs 1.12+/-0.24 and 3.95+/-0.34 vs 1.20+/-0.19, and LSD-t values
      were 2.49, 3.28, 3.25, 3.80 and 2.75, as compared with the control group, P is
      less than 0.01; the protein expression levels were 1.96+/-0.07 vs 0.45+/-0.07,
      0.53+/-0.07 vs 0.22+/-0.02, 1.32+/-0.06 vs 0.59+/-0.03, 1.51+/-0.23 vs 0.36+/
      0.09 and 0.57+/-0.01 vs 0.29+/-0.01, and LSD-t values were 1.51, 0.31, 0.73, 1.14
      and 0.28, P is less than 0.01. Administration of PPARg agonist rosiglitazone
      and/or Ad-PPARg significantly ameliorated hepatic steatosis, hepatocellular
      apoptosis, necro inflammation and fibrosis. These effects were associated with
      repressed expression of pro-apoptosis genes and up-regulated expression of anti
      apoptosis gene. After rosiglitazone treatment, the mRNA expression levels were
      3.78+/-0.58, 3.66+/-0.83, 3.04+/-0.37, 2.54+/-0.62 and 4.42+/-0.42, and LSD-t
      values were 0.18, 0.71, 1.23, 2.39 and 0.46, as compared with MCD group, the P
      values were 0.627, 0.241, less than 0.01, less than 0.01 and 0.278, the protein
      expression levels were 1.06+/-0.03, 0.30+/-0.01, 0.70+/-0.05, 1.19+/-0.30 and
      0.90+/-0.01, and LSD-t values were 0.90, 0.23, 0.62, 0.31 and 0.34, the P values
      were less than 0.01, less than 0.01, less than 0.01, 0.122, less than 0.01. After
      Ad-PPARg treatment, the mRNA expression levels were 2.31+/-0.16, 2.71+/-0.23,
      2.52+/-0.27, 1.79+/-0.32 and 5.97+/-0.72, and LSD-t values were 1.28, 1.66, 1.75,
      3.13 and 2.02, as compared with MCD group, P is less than 0.05; the protein
      expression levels were 1.73+/-0.07, 0.43+/-0.04, 1.01+/-0.08, 1.31+/-0.10 and
      1.56+/-0.04, and LSD-t values were 0.23, 0.10, 0.30, 0.20 and 0.99, with P values
      equal 0.009, 0.01, less than 0.01, 0.322 and less than 0.01. CONCLUSIONS: This
      study provided evidences for the protective role of activation and overexpression
      of PPARg in ameliorating hepatocellular apoptosis in mice with hepatic fibrosing
      steatohepatitis.

PMID- 22152245
TI  - [Serum and tissue expressions of galectin-3 in hepatocellular carcinoma and the
      clinical significances].
AB  - OBJECTIVE: To study the expression of Galectin-3 in human hepatocellular
      carcinoma (HCC) tissues and the clinical value of serum Galectin-3 in the
      diagnosis of hepatocellular carcinoma. METHODS: Immunohistochemistry method was
      used to detect the expression of Galectin-3 in the 46 pairs of HCC tissues and
      their para cancerous tissues. The relationship between expression levels of
      Galectin-3 and clinical parameters was analyzed. Serum Galectin-3 in different
      liver diseases were measured with ELISA. The sensitivity and specificity of
      galectin-3, alpha fetoprotein (AFP) and gamma-glutamyltranspeptidase II (GGT-II)
      for diagnosis of HCC were compared and the complementary diagnostic values of
      Galectin-3 and AFP and GGT-II for HCC were studied. RESULTS: (1) The positive
      rate of Galectin-3 in the tissue of HCC was 78.2%, dramatically higher than that
      in para cancerous tissues (15.2%) (P is less than 0.01). The expression levels
      were correlated with differentiation and with the high expression in poor
      differentiation tissues; (2) Based on ROC curve, the cut-off of serum Galectin-3
      for HCC diagnosis was set as 0.62mug/L, the serum galectin-3 positive rate was
      64.5% in HCC cases, which was apparently higher than that in liver cirrhosis,
      chronic hepatitis and healthy persons (P is less than 0.05); (3) Serum Galectin-3
      was not correlated with AFP and GGT-II. Combined determination of the three
      markers had the complementary diagnostic value for HCC and might increase the
      diagnostic sensitivity to 94.7%. CONCLUSION: Galectin-3 is overexpressed in HCC
      tissues and is correlated with the tumor differentiation, suggesting that
      Galectin-3 may be associated with the carcinogenesis and development of HCC.
      Serum galectin-3 increases in the HCC cases and combined determination of serum
      Galectin-3, AFP and GGT-II can increase the diagnostic efficiency for HCC.
      Galectin-3 could be a novel serum tumor marker for HCC.

PMID- 22152246
TI  - [Clinical effect and safety of liposomal-albendazole and tablet-albendazole for
      the treatment of human cystic echinococcosis].
AB  - OBJECTIVE: To explore and compare the clinical effect and safety of liposomal
      albendazole (L-ABZ) and tablet-albendazole (T-ABZ) in the treatment of cystic
      echinococcosis (CE1, CE2, and CE3). METHODS: A total of 269 cases treated with
      cystic echinococcosis (CE) in Xinjiang Medical University the First Affiliated
      Hospital from 1998 to 2008 were reviewed. 51 cases were excluded and 218 cases
      were enrolled in this research by retrospective case-control method. Among 110
      cases were treated with L-ABZ and 108 cases were treated with T-ABZ for short
      term (3 months) and long-term courses (6 months) respectively. The effects and
      safety of the two medicines were compared by analyzing the clinical symptoms,
      imaging check and serologic test results. RESULTS: In short-term effect
      evaluation, the total effective rates and curative rates of L-ABZ group and T-ABZ
      group were 77.9% and 49.1% vs 28.4% and 13.9%, respectively. The effects of L-ABZ
      group was better than that of T-ABZ group, with remarkable difference in total
      effective rates and curative rates (x2 value was 19.581, 6.877, respectively, P
      is less than 0.05). In long-term effect evaluation, the total effective rates and
      curative rates of L-ABZ and T-ABZ group were 81.7% and 49.0% vs 47.6% and 20.6%,
      respectively. There was significant difference between L-ABZ group and T-ABZ
      group in total effective rates and curative rates (x2 value was 20.977, 15.049,
      respectively, P is less than 0.05). In T-ABZ group the short-term curative rates
      were 50.0% (15/30), 8.8% (8/91) and 33.3% (7/21) respectively in CE1, CE2, and
      CE3, the short-term total effective rates were 56.7% (17/30), 35.2% (32/91) and
      61.9% (13/21) respectively in CE1, CE2, and CE3. The long-term curative rates
      were 58.3% (7/12), 28.6% (12/42) and 70.0% (7/10) respectively in CE1, CE2 and
      CE3, the long-term total effective rates were 75.0% (9/12), 69.0% (29/42) and
      100.0% (10/10) respectively in CE1, CE2, and CE3. When compared with CE2,
      differences existed in CE1 (x2 = 24.887, 4.329; P is less than 0.05) and CE3
      groups (x2 = 8.860, 5.076; P is less than 0.05) in terms of short-term effects.
      In L-ABZ group, the short-term curative rates were 47.4% (18/38), 12.2% (12/98)
      and 61.5% (8/13) respectively in CE1, CE2 and CE3, the short-term total effective
      rates were 92.1% (35/38), 65.3% (64/98) and 92.3% (12/13) respectively in CE1,
      CE2 and CE3, the long-term curative rates were 79.3% (23/29), 35.9% (23/64) and
      50.0% (3/6) respectively in CE1, CE2 and CE3, the long-term total effective rates
      were 96.6% (28/29), 84.4% (54/64) and 100% (6/6) respectively in CE1, CE2 and
      CE3. When compared with CE2, there were significant differences in CE1 (x2 =
      19.648, 9.930; P is less than 0.05) and CE3 groups (x2 = 18.880, 3.876; P is less
      than 0.05) in terms of short-term effect. In L-ABZ and T-ABZ groups, the drug
      related adverse effects were 11.1% (12/108) and 12.7% (14/110) respectively
      without significant difference (x2 = 0.155, P is more than 0.05). CONCLUSION: L
      ABZ and T-ABZ were both effective anti-echinococcosis drugs without dominant side
      effects. The clinical effect of L-ABZ was better than that of T-ABZ.

PMID- 22152247
TI  - [Aldosterone stimulates hepatic stellate cells contraction via Ca2+-independent
      pathways].
AB  - OBJECTIVE: To investigate the mechanisms of Aldosterone stimulating hepatic
      stellate cells(HSCs) contraction via Ca2+-independent pathways. METHODS: HSC-T6
      cell line was pre-disposed with Aldo 10mumol/L. The cell contraction was detected
      by silicone-rubber-membrane cultivation directly. The concentration variation of
      intracellular free calcium in rat HSC was observed by laser confocal microscopy.
      Besides, HSC-T6 cell line was under pre-disposal treatment with the blocking
      agents of Aldo receptor -antisterone, protein kinase C (PKC) special blocking
      agent-Stauro, Rho kinase blocking agent-Y27632 and MLCK special blocking agent-ML
      7 respectively prior to stimulation with aldosterone. RT-PCR was used to detect
      the expression of Rock2, RhoAGTP and RhoGEF in Ca2+- independent pathways
      mediated by Rho-kinase. RESULTS: Aldo could induce HSCs contraction. The
      concentration of intracellular free calcium in rat HSCs had no change after pre
      disposal treatment with Aldo. The mRNA expressions of Rock2, RhoAGTP and RhoGEF
      increased significantly after treatment with Aldo (0.770+/-0.049, 0.960+/-0.096,
      0.180+/-0.006, P is less than 0.01).When inhibited with antisterone, the mRNA
      expressions of the three elements were (0.440+/-0.166, 0.370+/-0.180 and 0.050+/
      0.001, P is less than 0.01), lower than that of Aldo group, but higher in ML
      7+Stauro + Aldo groups (0.940+/-0.066, 1.330+/-0.192 and 0.160+/-0.007, P is less
      than 0.05) as compared to the control group (0.140+/-0.023, 0.540+/-0.111 and
      0.110+/-0.012). In the Y27632 + ML-7 + Stauro+Aldo group, the mRNA expression of
      RhoGEF (0.290+/-0.004, P is less than 0.01)was higher than that of the ML-7 +
      Stauro + Aldo group (0.160+/-0.007). CONCLUSION: Aldo could induce HSCs
      contraction via Ca2+-independent pathways and Rho-Rock pathway involved in the
      process.

PMID- 22152248
TI  - [Relationship of NOR-1 with the regulation of inflammation via liver X receptor
      alpha in Kupffer cells].
AB  - OBJECTIVE: To investigate the relationship of NOR-1 with the inhibition of
      inflammatory reaction in mice Kupffer cells (KCs) induced by lipopolysaccharide
      (LPS) via liver X receptor alpha (LXR alpha). METHODS: KCs from male KM mice were
      isolated by density gradient centrifugation, incubated and then randomly assigned
      to three groups: control group, LPS treated group and LPS+T0901317 treated group.
      RESULTS: The mRNA and protein expressions of LXR alpha and NOR-1 in each group
      were determined by RT-PCR, immunofluorescent assay and western blot,
      respectively. The densities of TNF alpha and IL-10 in supernatants were evaluated
      by enzyme linked immunosorbent assay (ELISA). The mRNA and protein expression
      levels of LXR alpha in LPS + T0901317 group were the highest as compared to the
      other two groups (0.748+/-0.072 and 1.217+/-0.133 respectively), The mRNA and
      protein expression levels of NOR-1 in LPS+ T0901317 group were the highest as
      compared to the other two groups (2.726+/-0.065 and 0.842+/-0.058 respectively).
      The densities of supernatant TNF alpha in LPS group and IL-10 in LPS+T0901317
      group were the highest [(450.89+/-78.52) ng/L and (537.41+/-36.41) ng/L
      respectively]. CONCLUSIONS: Promoting the expression of LXR alpha in KCs can
      elevate the NOR-1 expression and then inhibit inflammatory reaction.

PMID- 22152249
TI  - [The role of glycogen synthase kinase-3 beta in the pathogenesis of liver
      ischemia reperfusion injury].
AB  - OBJECTIVE: To investigate the role of the key intracellular signaling molecule
      glycogen synthase kinase-3 beta in the mechanism of liver ischemia reperfusion
      (IR). METHODS: C57BL/6 mice were subjected to 90 min warm liver cephalad lobe
      ischemia, followed by various length of reperfusion. Experiment groups included
      sham control group, liver IRI model group and glycogen synthase kinase-3 beta
      inhibitor-treated group (SB216763 in DMSO, 25 g/kg, i.p, 2 hour prior to the
      onset of liver ischemia). The expression of glycogen synthase kinase-3 beta
      protein was analysed by Western blotting. The serum ALT levels were determined to
      reflect the function of liver. The affected liver lobes were harvested for
      histology analysis. The inflammatory gene expression was detected by Quantitative
      PCR. RESULTS: By western blot analysis, we found that ischemia itself activated
      glycogen synthase kinase-3 beta by a significant decrease of its phosphorylation.
      Glycogen synthase kinase-3 beta inhibitor SB216763-pretreatment ameliorated the
      liver damages significantly as compared to the controls (sALT: 2046+/-513 U/L vs
      5809+/-1689 U/L, P = 0.0153), and suppressed the gene expressions of IL-12, TNFa,
      IL-1b and IL-6. CONCLUSIONS: This study demonstrated that the ischemia process
      modulated liver innate immune activation via a GSK-3-dependent mechanism which
      favored the development of a pro-inflammation response and lead to liver tissue
      damages. GSK-3b may be a new therapeutic target to ameliorate liver IRI in
      transplant patients.

PMID- 22152250
TI  - [Efficacy comparison between bicyclol and polyene phosphatidylcholine treatments
      for the patients with nonalcoholic fatty liver disease].

PMID- 22152251
TI  - [Porcine endogenous retroviral secretion by primary pig hepatocytes cultured on
      chitosan nanofiber scaffold].

PMID- 22152252
TI  - [Expression profile of miRNA in PBMCs of chronic severe hepatitis B patients].

PMID- 22152253
TI  - [A case report of chronic hepatitis B and hepatitis C patient with type 2
      diabetes].

PMID- 22152254
TI  - [Von Meyenburg syndrome: a case report].

PMID- 22152255
TI  - 3D Echo systematically underestimates right ventricular volumes compared to
      cardiovascular magnetic resonance in adult congenital heart disease patients with
      moderate or severe RV dilatation.
AB  - BACKGROUND: Three dimensional echo is a relatively new technique which may offer
      a rapid alternative for the examination of the right heart. However its role in
      patients with non-standard ventricular size or anatomy is unclear. This study
      compared volumetric measurements of the right ventricle in 25 patients with adult
      congenital heart disease using both cardiovascular magnetic resonance (CMR) and
      three dimensional echocardiography. METHODS: Patients were grouped by diagnosis
      into those expected to have normal or near-normal RV size (patients with repaired
      coarctation of the aorta) and patients expected to have moderate or worse RV
      enlargement (patients with repaired tetralogy of Fallot or transposition of the
      great arteries). Right ventricular end diastolic volume, end systolic volume and
      ejection fraction were compared using both methods with CMR regarded as the
      reference standard RESULTS: Bland-Altman analysis of the 25 patients demonstrated
      that for both RV EDV and RV ESV, there was a significant and systematic under
      estimation of volume by 3D echo compared to CMR. This bias led to a mean
      underestimation of RV EDV by -34% (95%CI: -91% to + 23%). The degree of
      underestimation was more marked for RV ESV with a bias of -42% (95%CI: -117% to +
      32%). There was also a tendency to overestimate RV EF by 3D echo with a bias of
      approximately 13% (95% CI -52% to +27%). CONCLUSIONS: Statistically significant
      and clinically meaningful differences in volumetric measurements were observed
      between the two techniques. Three dimensional echocardiography does not appear
      ready for routine clinical use in RV assessment in congenital heart disease
      patients with more than mild RV dilatation at the current time.

PMID- 22152256
TI  - Falls among the elderly.

PMID- 22152258
TI  - When evidence is not enough: the challenge of implementing fall prevention
      strategies.
AB  - PROBLEM: As the evidence-based movement has advanced in public health, changes in
      public health practices have lagged far behind creating a science to service gap.
      For example, science has produced effective falls prevention interventions for
      older adults. It now is clearer WHAT needs to be done to reduce injury and death
      related to falls. However, issues have arisen regarding HOW to assure the full
      and effective uses of evidence-based programs in practice. SUMMARY: Lessons
      learned from the science and practice of implementation provide guidance for how
      to change practices by developing new competencies, how to change organizations
      to support evidence-based practices, and how to change public health systems to
      align system functions with desired practices. The combination of practice,
      organization, and system change likely will produce the public health benefits
      that are the promise of evidence-based falls prevention interventions. IMPACT ON
      PUBLIC HEALTH: For the past several decades, the emphasis has been solely on
      evidence-based interventions. Public health will benefit from giving equal
      emphasis to evidence-based implementation. IMPACT ON INDUSTRY: We now have over
      two decades of research on the effectiveness of fall prevention interventions.
      The quality of this research is judged by a number of credible international
      organizations, including the Cochrane Collaboration (http://www.cochrane.org/),
      the American and British Geriatrics Societies, and the Campbell Collaboration
      (http://www.campbellcollaboration.org/). These international bodies were formed
      to ponder and answer questions related to the quality and relevance of research.
      These developments are a good first step. However, while knowing WHAT to do (an
      evidence-based intervention) is critical, we also need to know HOW to effectively
      implement the evidence. Implementation, organization change, and system change
      methods produce the conditions that allow and support the full and effective use
      of evidence-based interventions. It is time to focus on utilization of
      implementation knowledge in public health. Without this focus the vast amount on
      new evidence being generated on the prevention of falls and related injuries
      among older adults will have little impact on their health and safety.

PMID- 22152259
TI  - What does it mean to transform knowledge into action in falls prevention
      research? Perspectives from the Canadian Institutes of Health Research.
AB  - INTRODUCTION: The concept of knowledge translation as defined by the Canadian
      Institutes for Health Research and the Knowledge to Action Cycle, described by
      Graham et al (Graham et al., 2006), are used to make a case for the importance of
      using a conceptual model to describe moving knowledge into action in the area of
      falls prevention. METHOD: There is a large body of research in the area of falls
      prevention. It would seem that in many areas it is clear what is needed to
      prevent falls and further syntheses can determine where the evidence is
      sufficiently robust to warrant its implementation as well as where the gaps are
      that require further basic research. CONCLUSION: The phases of the action cycle
      highlight seven areas that should be paid attention to in order to maximize
      chances of successful implementation.

PMID- 22152260
TI  - Closing the gap: a research agenda to accelerate the adoption and effective use
      of proven older adult fall prevention strategies.
AB  - INTRODUCTION: To make an impact on the public's health, evidence-based
      interventions must be disseminated broadly, supported by training and technical
      assistance, adopted widely, and implemented as designed. Many effective older
      adult fall prevention interventions have been identified, but too few have gained
      wide community acceptance and little is known about the best ways to encourage
      their broader use. Therefore, as in many other fields, fall prevention suffers
      from a wide gap between scientific discoveries and their everyday use. METHOD:
      This article articulates the key activities embedded in Step 4 of the public
      health model-specifically translation and dissemination to ensure widespread
      adoption and use-in order to illuminate critical research needs in older adult
      fall prevention. CONCLUSIONS: These needs, if addressed, will help close the gap
      between research and practice.

PMID- 22152261
TI  - Translation of falls prevention knowledge into action in hospitals: what should
      be translated and how should it be done?
AB  - INTRODUCTION: Falls prevention evidence has changed and evolved over time with
      positive and negative studies revealing that a "one-size fits all" approach is
      not the solution. Care must be taken to critically appraise the evidence and the
      potential applicability of that evidence to the specific hospital setting.
      METHOD: A narrative account of the evolution of research evidence in this field
      is first presented. How this evidence should be applied in clinical practice is
      challenging, with a lack of translational evidence for the hospital setting we
      draw on broader theory of translating knowledge to action. CONCLUSIONS: The
      journey should begin with formation of a management and engagement committee. A
      review of existing practices and the difference between existing practice and
      evidence-based practice should be undertaken to identify the "evidence-practice
      gap." Engagement with staff is recommended to inform a plan for practice change.
      Plans for resourcing, targeting, and evaluating these strategies should also be
      undertaken. IMPACT ON INDUSTRY: This paper will assist hospitals to identify and
      implement evidence based falls prevention strategies leading to an improvement in
      patient safety.

PMID- 22152262
TI  - Implementing the evidence for preventing falls among community-dwelling older
      people: a systematic review.
AB  - PROBLEM AND OBJECTIVE: The translation of the evidence-base for preventing falls
      among community-dwelling older people into practice has been limited. This study
      systematically reviewed and synthesised the effectiveness of methods to implement
      falls prevention programmes with this population. METHODS: Articles published
      between 1980 and May 2010 that evaluated the effects of an implementation
      strategy. No design restrictions were imposed. A narrative synthesis was
      undertaken. RESULTS: 15 studies were identified. Interventions that involved the
      active training of healthcare professionals improved implementation. The evidence
      around changing the way people who fall are managed within primary care
      practices, and, layperson, peer or community delivered models was mixed. IMPACT
      ON INDUSTRY: Translating the evidence-base into practice involves changing the
      attitudes and behaviours of older people, healthcare professionals and
      organisations. However, there is a need for further evaluation on how this can be
      best achieved.

PMID- 22152263
TI  - Knowledge translation for falls prevention: the view from Canada.
AB  - Researchers have now conclusively demonstrated that many falls in older adults
      can be prevented, and that the interventions can produce cost-savings. Because
      most falls are multifactorial, falls prevention interventions can involve several
      approaches delivered by numerous health care professions in multiple settings.
      These complexities may make knowledge translation (KT) more challenging than with
      simpler interventions for specific diseases. After describing these complexities
      and reviewing the evidence base for falls prevention, this paper examines the few
      published demonstrations of KT in falls prevention. It continues with a
      description of the visibility and accessibility of falls prevention Clinical
      Practice Guidelines (CPGs) on the websites of four key Canadian health
      professional associations: nurses, occupational therapists, physical therapists,
      and physicians. The paper concludes with a review of published studies of KT in
      falls prevention in Canadian health care settings, including research on care or
      treatment gaps in falls prevention and the uptake of CPGs. IMPACT ON INDUSTRY:
      Those in the long term care and hospital industries may use the findings when
      considering fall prevention programs. This paper does not cover occupational
      falls, and participants in the referenced studies will be past conventional
      retirement age.

PMID- 22152264
TI  - Falls and fall prevention programmes in developing countries: environmental scan
      for the adaptation of the Canadian Falls prevention curriculum for developing
      countries.
AB  - PROBLEM: Falls in older persons in developing countries are poorly understood,
      and falls prevention and health promotion programmes for this population are
      largely lacking. METHODS: A systematic review was carried out of relevant
      literature on falls and prevention programmes, and falls prevention education,
      and a scan undertaken of health promotion programmes for older persons in a
      representative country - South Africa. RESULTS: Studies on the risk and
      prevalence of falls are largely retrospective and hospital-based, with varied
      methodology, including study period, sampling method and sample size. Falls
      prevalence is based largely on self-reports in studies on general trauma in all
      age groups. Falls incidence varies from 10.1% to 54%. No reports could be traced
      on sustained falls prevention or health promotion programmes. CONCLUSION: Scant
      research has been conducted and little preventive education offered on falls in
      older persons. Adaptation of the Canadian Falls Prevention Curriculum for
      developing countries will help to fill gaps in knowledge and practice. IMPACT ON
      INDUSTRY: With rapid increase in the populations of older persons in developing
      countries, research on age related disorders such as falls is required to guide
      policy and management of falls.

PMID- 22152265
TI  - Reducing fall risk by improving balance control: development, evaluation and
      knowledge-translation of new approaches.
AB  - PROBLEM: Falling is a leading cause of serious injury, loss of independence, and
      nursing-home admission in older adults. Impaired balance control is a major
      contributing factor. METHODS: Results from our balance-control studies have been
      applied in the development of new and improved interventions and assessment
      tools. Initiatives to facilitate knowledge-translation of this work include
      setting up a new network of balance clinics, a research-user network and a
      research-user advisory board. RESULTS: Our findings support the efficacy of the
      developed balance-training methods, balance-enhancing footwear, neuro-prosthesis,
      walker design, handrail-cueing system, and handrail-design recommendations in
      improving specific aspects of balance control. IMPACT ON KNOWLEDGE USERS: A new
      balance-assessment tool has been implemented in the first new balance clinic, a
      new balance-enhancing insole is available through pharmacies and other commercial
      outlets, and handrail design recommendations have been incorporated into 10
      Canadian and American building codes. Work in progress is expected to have
      further impact.

PMID- 22152266
TI  - Projections of hospitalised fall-related injury in NSW, Australia: impacts on the
      hospital and aged care sectors.
AB  - Projections of the number, rate and cost of fall-related hospitalised injuries
      for individuals aged 65 years and older in New South Wales (NSW), Australia were
      estimated to 2051 for two scenarios: (1) demographic change only using 2008
      admission rates; and (2) modelled change using negative binominal regression
      taking into account current trends in admission rates. Based on demographic
      change alone, the number and cost of fall injury hospitalisations among older
      people is expected to increase almost three-fold by 2051. Transfers to permanent
      residential aged care will also increase 3.2 fold. However, if the fall-related
      hospitalisation rate sustains its current trend, these increases are projected to
      be more than ten-fold by 2051. Even with demographic change alone, there will be
      a significant impact on the resources required to care for older people suffering
      a fall injury hospitalisation over the next forty years in NSW. The impact on the
      hospital and aged care sectors will be considerable unless significant
      improvements occur in the prevention and treatment of fall-related injury in
      older people.

PMID- 22152267
TI  - Validating an evidence-based, self-rated fall risk questionnaire (FRQ) for older
      adults.
AB  - BACKGROUND: Falls are a common, serious, and often unrecognized problem facing
      older adults. The objective of this study was to provide an initial clinical and
      statistical validation for a public health strategy of fall risk self-assessment
      by older adults using a Fall Risk Questionnaire (FRQ). METHODS: Adults age 65+
      (n=40) were recruited at a Los Angeles Veterans Affairs (VA) medical facility and
      at a local assisted living facility. Participants completed the FRQ self
      assessment and results were compared to a "gold standard" of a clinical
      evaluation of risks using the American/British Geriatrics Society guidelines to
      assess independent predictors of falls: history of previous falls, fear of
      falling, gait/balance, muscle weakness, incontinence, sensation and
      proprioception, depression, vision, and medications. For the comparison, we used
      an iterative statistical approach, weighing items based on relative risk.
      RESULTS: There was strong agreement between the FRQ and clinical evaluation
      (kappa=.875, p<.0001). Individual item kappa values ranged from .305-.832. After
      dropping one FRQ item (vision risk) because of inadequate agreement with the
      clinical evaluation (kappa=.139, p=.321), the final FRQ had good concurrent
      validity. CONCLUSIONS: The FRQ goes beyond existing screening tools in that it is
      based on both evidence and clinical acceptability and has been initially
      validated with clinical examination data. A larger validation with longitudinal
      follow-up should determine the actual strength of the FRQ in predicting future
      falls.

PMID- 22152268
TI  - Evaluation of an evidence-based education program for health professionals: the
      Canadian Falls Prevention Curriculum(c) (CFPC).
AB  - INTRODUCTION: A staged, mixed methods approach was applied to the development and
      evaluation of an evidence-based education program for health care professionals
      and community leaders on how to design, implement and evaluate a fall prevention
      program. Stages included pre-development, development, pilot testing and impact
      on practice. The goal of the evaluation was to determine if the Canadian Falls
      Prevention Curriculum met the needs of the target audience and had an impact on
      learning and practice. METHODS: Methods included a needs assessment, systematic
      reviews, pre-post tests of learning, follow-up surveys and interviews, and
      descriptive reports of stakeholder involvement. The needs assessment and
      systematic review of existing programs indicated that there was a demand for a
      comprehensive, evidence-based curriculum on fall prevention and that no similar
      curricula existed. Pre-post test findings showed significant increases in
      learning and follow-up surveys showed a positive impact on practice. IMPACT ON
      INDUSTRY: Evidence shows that the most effective fall prevention efforts are
      those that address the multifactorial nature of fall risk, with proven
      interventions provided by trained clinicians. The Canadian Falls Prevention
      Curriculum provides evidence-based training for clinicians and community leaders
      using a public health approach to fall prevention that includes instruction on
      how to define the problem, assess the risk, examine best practices, implement the
      program, and conduct evaluation of the program's effectiveness.

PMID- 22152269
TI  - Using the RE-AIM framework to translate a research-based falls prevention
      intervention into a community-based program: lessons learned.
AB  - PROBLEM: Exercise-based research interventions demonstrate reduced risk and rates
      of falls for community dwelling older adults; however, little is known about
      effective mechanisms for the translation, implementation, and maintenance of
      these interventions in community settings. METHOD: The RE-AIM framework was used
      to assess the translatability of an effective exercise-based research
      intervention in a community setting. Questions included: Reach - Would the target
      population attend? Effectiveness - What was the adherence and compliance to the
      program? Were there individual improvements in falls risk factors? Adoption:
      Would staff at the center adopt the program and offer it past the funding period?
      Implementation - What adaptations, including optimal frequency and duration,
      should be made to meet the community needs, still adhere to core elements and
      achieve similar outcomes? Maintenance - Would the program be sustained by our
      community partners? DISCUSSION: The process of translating a controlled research
      intervention targeting older adults at risk of falls into a community setting was
      challenging. Licensed professionals developed the infrastructure to safely and
      effectively deliver the program. The end product was highly appealing program to
      our target audience, resulted in improved outcomes and was successfully adopted
      and maintained by the community partner. SUMMARY: Partnerships between community
      and healthcare providers are key to successful implementation of falls prevention
      interventions. Lessons learned from this experience can be applied to the
      translation of future exercise-based falls prevention interventions.

PMID- 22152270
TI  - Implementing falls prevention research into policy and practice in Australia:
      past, present and future.
AB  - INTRODUCTION: Falls in older Australians are a significant public health issue
      with one in three older people falling one or more times each year. METHOD: Many
      fall prevention randomized controlled trials have been conducted in Australia as
      well as across the world. RESULTS: The findings of these studies now constitute a
      substantial evidence base that can provide direction for health and lifestyle
      interventions for preventing falls in older people. This research evidence has
      contributed to health policy in Australia to some extent, but is yet to be widely
      implemented into practice. This opinion piece overviews previous policy
      initiatives and describes a new Partnership research program funded by the
      Australian National Health and Medical Research Council (NHMRC), which seeks to
      further influence health policy and address the ongoing research-practice gap.

PMID- 22152271
TI  - The National Falls FreeTM Initiative, working collaboratively to affect change.
AB  - INTRODUCTION: Since 2004 the National Council on Aging (NCOA) has been working in
      collaboration with a growing number of national, state, and local organizations
      through the Falls Free((c)) Initiative to address the growing public health issue
      of falls and fall-related injuries among older adults. Through collaborative
      leadership, evidence-based interventions, practical lifestyle adjustments, and
      community partnerships we are working to reduce the number of older adult falls.
      IMPACT ON INDUSTRY: The many activities of the national and state coalitions have
      brought recognition to the issue of fall prevention, education, and training to
      providers and greater investment in programs and services resulting in tremendous
      momentum and community activism. While we have yet to realize an impact on rates
      of falls, this strategic investment in building the infrastructure needed to
      affect change is the first step toward reducing the growing number of falls among
      older adults.

PMID- 22152272
TI  - Utilizing quality improvement methods to prevent falls and injury from falls:
      enhancing resident safety in long-term care.
AB  - INTRODUCTION: Internationally, the growing evidence related to preventable
      adverse events within healthcare settings has resulted in the creation of
      numerous patient safety and quality improvement initiatives. In Canada, Safer
      Healthcare Now!, a national patient safety initiative of the Canadian Patient
      Safety Institute, and the Registered Nurses' Association of Ontario, the
      professional association representing registered nurses in Ontario, have
      partnered to combine quality improvement expertise with evidence-based practice
      expertise to accelerate improvement in the area of falls prevention and injury
      reduction. The synergistic relationship between Safer Healthcare Now! and the
      Registered Nurses' Association of Ontario has resulted in the evolution of the
      Safer Healthcare Now! national Falls Prevention intervention. The ultimate goal
      of the Falls Prevention intervention is to improve care by translating "what we
      know" into "what we do," by supporting quality improvement teams to make changes
      at the local level to enhance the patient experience. METHOD: This article
      provides an overview of Safer Healthcare Now! as a national patient safety
      initiative, and highlights the results of a National Collaborative on Falls
      Prevention as a knowledge translation strategy utilized within the long-term care
      setting. A description of expanding supports for knowledge translation will also
      be provided.

PMID- 22152273
TI  - Preventing falls among seniors: the way forward.
AB  - There is a growing body of research about the etiology and prevention of falls.
      However, the persistently high incidence of falls among seniors calls for renewed
      efforts to develop, test, implement, and scale-up fall prevention strategies for
      older adults. This paper considers advances in the field and describes three
      priority areas for generating research and translating knowledge on fall
      prevention. Clinical practice guidelines, systems change approaches and
      environmental risk factors are discussed. Recommendations include transcending
      our health sector view of the fall prevention problem, supporting comparative
      research on system-oriented approaches to fall prevention, and examining ways to
      sustain and scale-up fall prevention efforts.

PMID- 22152274
TI  - Abstracts of the Twentieth Annual Computational Neuroscience Meeting, CNS*2011.
      Stockholm, Sweden. July 23-28, 2011.

PMID- 22152275
TI  - The ICU follow-up clinic: a new paradigm for intensivists.
AB  - Over the last 15 years the management of patients admitted in the ICU has changed
      dramatically. A growing number of well designed randomized controlled studies
      have been published, resulting in improved medical care and reduction of short
      term morbidity and mortality. Despite these  important achievements, little
      attention has been placed on the long-term complications of subjects discharged
      from the ICU. This review will focus on the most common long-term outcomes post
      ICU admission, and will emphasize the importance of developing ICU clinics to
      provide comprehensive  care to ICU survivors. We also describe our experience
      regarding the organization, functioning, and limitations for the development of
      our post-ICU clinic.

PMID- 22152276
TI  - The effect of glucocorticoids on sex steroid synthesis in cultured Taenia
      crassiceps Wake Forest University (WFU) cysticerci.
AB  - We have shown previously that cultured Taenia crassiceps Wake Forest University
      (WFU) and Taenia solium cysticerci, as well as the adult worms, synthesize sex
      steroid hormones from [3H]steroid precursors and that androgens and oestrogens
      influence the in vitro development of the parasites. Glucocorticoids (GCs) are
      used to control the inflammation caused by T. solium cysticerci in the brain.
      These steroids stimulate oestrogen synthesis in several tissues. Since there is
      no information on the effect of GC on the endocrine function of cysticerci, we
      investigated the effect of natural and synthetic GCs on the synthesis of
      oestrogens in cultured T. crassiceps WFU cysticerci. The cysticerci were obtained
      from the peritoneal cavity of infected female BALB/c mice; the cysts were washed
      extensively and pre-cultured in Dulbecco's Modified Eagle's Medium (DMEM) plus
      antibiotics for 5 days. The parasites were further cultured with different doses
      of corticosterone, dexamethasone or the vehicle for 5 days.
      [3H]Dehydroepiandrosterone (3H-DHEA) was added to the media and the cysticerci
      were further incubated for 6 or 24 h. Media were then removed and the steroids
      ether-extracted. Aliquots of the media were seeded on silica gel plates and
      developed in solvent systems. Parasites incubated in the presence of 3H-DHEA
      synthesized [3H]androstenediol, [3H]testosterone and [3H]17beta-oestradiol
      ([3H]17beta-E2). The addition of 100 nm or higher corticosterone doses to the
      media increased [3H]17beta-E2 synthesis fourfold after 24 h. Dexamethasone also
      increased [3H]17beta-E2 synthesis. The experiments presented here show for the
      first time that corticosterone and the synthetic GC dexamethasone modulate the
      synthesis of oestrogens by cysticerci.

PMID- 22152277
TI  - Atherosclerosis in young Brazilians suffering violent deaths: a pathological
      study.
AB  - BACKGROUND: Atherosclerosis is the leading cause of coronary heart disease and
      ischemic stroke, which can cause sudden death in adulthood. In general, the
      clinical manifestations of cardiovascular diseases are caused by atherosclerosis,
      which is a process that starts during middle age. More recent studies indicate
      that the atherosclerotic process begins during childhood. METHODS: To evaluate
      the extent of atherosclerotic disease in young Brazilians, we conducted a study
      of the pathological alterations in the major arteries of victims of violent
      death. Samples of the right carotid artery, left coronary artery, and thoracic
      aorta of young victims of violent death were analyzed and graded in accordance
      with the histological atherosclerotic lesion types proposed by the American Heart
      Association. Samples were collected from 100 individuals who had died from
      external causes, aged from 12 to 33 years. RESULTS: The majority of cases (83%)
      were male, and 66% of deaths were homicides caused by firearms. The median age
      was 20.0 years and mean body mass index was 20.9 kg/m2. Of the right carotid
      artery specimens, 3% were normal, 55% had type I, 40% had type II, 1% had type
      III, and 1% had type IV atherosclerotic lesions. Of the left coronary artery
      specimens, 5% were normal, 48% had type I, 41% had type II, 3% had type III, and
      3% had type IV lesions. Of the thoracic aorta specimens, none were normal, 13%
      had type I, 64% had type II, 22% had type III, and 1% had type IV lesions.
      Overall, 97.34% of arteries examined had some degree of atherosclerosis. The most
      common histological type was type II (foam cells). No thoracic aorta specimens
      were normal, and the coronary artery specimens had the most atherosclerosis.
      CONCLUSIONS: Our results show a high prevalence of atherosclerotic lesions among
      young people in Brazil. Intervention should be undertaken to decrease the rate of
      sudden cardiac death in the adult population.

PMID- 22152278
TI  - Adaptive Muller cell responses to microglial activation mediate neuroprotection
      and coordinate inflammation in the retina.
AB  - PURPOSE: Microglia and Muller cells are prominent participants in retinal
      responses to injury and disease that shape eventual tissue adaptation or damage.
      This investigation examined how microglia and Muller cells interact with each
      other following initial microglial activation. METHODS: Mouse Muller cells were
      cultured alone, or co-cultured with activated or unactivated retinal microglia,
      and their morphological, molecular, and functional responses were evaluated.
      Muller cell-feedback signaling to microglia was studied using Muller cell
      conditioned media. Corroborative in vivo analyses of retinal microglia-Muller
      cell interactions in the mouse retina were also performed. RESULTS: Our results
      demonstrate that Muller cells exposed to activated microglia, relative to those
      cultured alone or with unactivated microglia, exhibit marked alterations in cell
      morphology and gene expression that differed from those seen in chronic gliosis.
      These Muller cells demonstrated in vitro (1) an upregulation of growth factors
      such as GDNF and LIF, and provide neuroprotection to photoreceptor cells, (2)
      increased pro-inflammatory factor production, which in turn increased microglial
      activation in a positive feedback loop, and (3) upregulated chemokine and
      adhesion protein expression, which allowed Muller cells to attract and adhere to
      microglia. In vivo activation of microglia by intravitreal injection of
      lipopolysaccharide (LPS) also induced increased Muller cell-microglia adhesion,
      indicating that activated microglia may translocate intraretinally in a radial
      direction using Muller cell processes as an adhesive scaffold. CONCLUSION: Our
      findings demonstrate that activated microglia are able to influence Muller cells
      directly, and initiate a program of bidirectional microglia-Muller cell signaling
      that can mediate adaptive responses within the retina following injury. In the
      acute aftermath following initial microglia activation, Muller cell responses may
      serve to augment initial inflammatory responses across retinal lamina and to
      guide the intraretinal mobilization of migratory microglia using chemotactic cues
      and adhesive cell contacts. Understanding adaptive microglia-Muller cell
      interactions in injury responses can help discover therapeutic cellular targets
      for intervention in retinal disease.

PMID- 22152280
TI  - HDL-C: role as a risk modifier.
AB  - Evidence that low-density lipoprotein-cholesterol (LDL-C) causes cardiovascular
      disease (CVD) is overwhelming. It has also been proven beyond all doubt that
      lowering the level of LDL-C using statins reduces CV risk. However, many people
      remain at high risk even when their level of LDL-C has been reduced by aggressive
      treatment with statins. One reason for this residual risk can be a low level of
      high-density lipoprotein-cholesterol (HDL-C). The concentration of HDL-C is an
      independent, inverse predictor for CVD. This relationship is apparent even when
      treatment with statins has reduced the level of LDL-C to below 1.8 mmol/L (70
      mg/dL). It has therefore been suggested that raising the level of HDL-C should be
      considered as a therapeutic strategy for reducing the residual CV risk that
      persists in some people, despite aggressive LDL-C lowering with statins. HDL
      particles have several functions with the potential to protect against arterial
      disease, the best known of which relates to their ability to promote cholesterol
      efflux from macrophages in the artery wall. However, HDLs have several additional
      protective properties that are independent of their involvement in cholesterol
      metabolism. For example, they have properties that reduce oxidation, vascular
      inflammation and thrombosis, improve endothelial function, promote endothelial
      repair, enhance insulin sensitivity and promote insulin secretion by pancreatic
      beta islet cells. There is also a large and compelling body of evidence in animal
      models showing that interventions that increase HDL levels are profoundly anti
      atherogenic. Major causes of low HDL are abdominal obesity and type 2 diabetes,
      the worldwide incidences of which are increasing at alarming rates. Strategies to
      increase the concentration of HDL should begin with lifestyle changes such as
      weight reduction, increased physical activity and smoking cessation. However,
      compliance with such measures is frequently poor and pharmacological intervention
      may be required. Currently available HDL-raising medications include fibrates,
      niacin and statins. There is indisputable evidence that lowering LDL-C levels
      using statins translates into a large reduction in CV risk. There is also
      mounting evidence that increasing the level of HDL-C using statins contributes to
      an additional reduction in CV risk. For example, the increase in HDL-C levels
      that was associated with simvastatin treatment in the 4S study was a significant
      predictor for the reduction in CV events. Moreover, a meta-analysis of 1,455
      patients in 4 coronary intravascular ultrasound imaging trials showed that both
      the achieved level of LDL-C and the increase in HDL-C concentration during statin
      treatment were significant independent predictors for coronary atheroma
      progression as assessed by coronary intravascular ultrasound. In conclusion,
      evidence suggests that low levels of HDL-C are associated with an increased CV
      risk even when LDL-C is reduced to below 1.7 mmol/L (70 mg/dL) with a statin.
      Moreover, there is mounting evidence that increasing the level of HDL-C has the
      capacity to reduce CV risk. Thus, there is a compelling case for targeting both
      the LDL and HDL fractions to reduce CV risk in people with dyslipidemia, high CV
      risk and low levels of HDL-C.

PMID- 22152279
TI  - The impact of sleep quality on cognitive functioning in Parkinson's disease.
AB  - In healthy individuals and those with insomnia, poor sleep quality is associated
      with decrements in performance on tests of cognition, especially executive
      function. Sleep disturbances and cognitive deficits are both prevalent in
      Parkinson's disease (PD). Sleep problems occur in over 75% of patients, with
      sleep fragmentation and decreased sleep efficiency being the most common sleep
      complaints, but their relation to cognition is unknown. We examined the
      association between sleep quality and cognition in PD. In 35 non-demented
      individuals with PD and 18 normal control adults (NC), sleep was measured using
      24-hr wrist actigraphy over 7 days. Cognitive domains tested included attention
      and executive function, memory and psychomotor function. In both groups, poor
      sleep was associated with worse performance on tests of attention/executive
      function but not memory or psychomotor function. In the PD group,
      attention/executive function was predicted by sleep efficiency, whereas memory
      and psychomotor function were not predicted by sleep quality. Psychomotor and
      memory function were predicted by motor symptom severity. This study is the first
      to demonstrate that sleep quality in PD is significantly correlated with
      cognition and that it differentially impacts attention and executive function,
      thereby furthering our understanding of the link between sleep and cognition.

PMID- 22152281
TI  - Pitavastatin: an overview.
AB  - Compared to other statins, pitavastatin is a highly potent 3-hydroxy-3-methyl
      glutaryl-CoA (HMG-CoA) reductase inhibitor and an efficient hepatocyte low
      density lipoprotein-cholesterol (LDL-C) receptor inducer. Its characteristic
      structure (heptenoate as the basic structure, a core quinoline ring and side
      chains that include fluorophenyl and cyclopropyl moieties) provides improved
      pharmacokinetics and significant LDL-C-lowering efficacy at low doses. Unlike
      other statins, the cyclopropyl group on the pitavastatin molecule appears to
      divert the drug away from metabolism by cytochrome P450 (CYP) 3 A4 and allows
      only a small degree of clinically insignificant metabolism by CYP2C9. As a
      result, pitavastatin is minimally metabolized; most of the bioavailable fraction
      of an oral dose is excreted unchanged in the bile and is reabsorbed by the small
      intestine ready for enterohepatic recirculation. This process probably accounts
      for pitavastatin's increased bioavailability relative to most other statins and
      contributes to its prolonged duration of action. In addition to its potent LDL-C
      lowering efficacy, a number of pleiotropic benefits that might lead to a
      reduction in residual risk have been suggested in vitro. These include beneficial
      effects on endothelial function, stabilisation of the coronary plaque, anti
      inflammatory effects and anti-oxidation. With regard to the clinical safety and
      efficacy of pitavastatin, the Phase IV Collaborative study of
      Hypercholesterolemia drug Intervention and their Benefits for Atherosclerosis
      prevention (CHIBA study) showed similar changes in lipid profile with
      pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia.
      However, a subgroup analysis of the CHIBA study showed that pitavastatin produced
      more significant changes from baseline in LDL-C, TG, and HDL-C in patients with
      hypercholesterolemia and metabolic syndrome. The clinical usefulness of
      pitavastatin has been further demonstrated in a number of Japanese patient groups
      with hypercholesterolemia, including those with insulin resistance, low levels of
      high-density lipoprotein-cholesterol (HDL-C), high levels of C-reactive protein,
      and chronic kidney disease. Finally, the Japan Assessment of Pitavastatin and
      AtorvastatiN in Acute Coronary Syndrome (JAPAN-ACS) study showed that
      pitavastatin induces plaque regression in patients with ACS, which suggests
      potential benefits for pitavastatin in reducing CV risk.

PMID- 22152282
TI  - Pitavastatin: novel effects on lipid parameters.
AB  - Atherogenic dyslipidemia is characterised by high levels of triglycerides, low
      levels of high-density lipoprotein-cholesterol (HDL-C), and moderate to marked
      elevations in low-density lipoprotein-cholesterol (LDL-C) concentrations; such
      dyslipidemia is further characterised by high apolipoprotein B (apoB):
      apolipoprotein A1 (apoA1) ratios. Numerous clinical trials have demonstrated that
      statins are effective in lowering LDL-C and reducing cardiovascular (CV) risk in
      people with dyslipidemia. However, the most effective treatments should target
      all of the key atherogenic features, rather than LDL-C alone. Pitavastatin is a
      new member of the statin class whose distinct pharmacological features translate
      into a broad spectrum of action on both apoB-containing and apoA1-containing
      lipoprotein components of the atherogenic lipid profile. The efficacy and safety
      of this statin has been demonstrated by a large clinical development programme
      conducted both in Japanese and Caucasian populations. Phase III and IV studies in
      a wide range of patients with primary hypercholesterolemia or combined
      dyslipidemia showed that 12 weeks' treatment with pitavastatin l-4 mg was well
      tolerated, significantly improved lipid profiles (including LDL-C, TG, and HDL-C
      levels) and increased the EAS-/NCEP ATP Ill-recommended LDL-C target attainment
      rate to a similar or greater degree as comparable doses of atorvastatin,
      simvastatin, or pravastatin. Results were similar across all patient groups and
      were generally sustained after 52 weeks of treatment. However, whereas the
      effects of atorvastatin and simvastatin on HDL-C levels remained constant over
      the long term, pitavastatin-treated patients experienced progressive and
      maintained elevations in HDL-C, ultimately increasing by up to 14.3% vs. initial
      baseline. In this context, it is significant that the in vitro studies of
      Yamashita et al. [J Atheroscler Thromb 2010;17:436-51] have shown pitavastatin to
      be distinguished by its potent stimulation of apoA1 production in hepatocyte-like
      cells. These findings suggest that pitavastatin may be highly efficacious in
      raising levels of lipid-poor apoA1 particles, which are known to be highly active
      in ABCA1-mediated cellular cholesterol efflux, an observation which is pertinent
      to the excessive accumulation of cholesterol in macrophage foam cells of the
      atherosclerotic plaque. Indeed, the intravascular remodelling and maturation of
      lipid-poor apoA1 particles is known to drive flux of apoA1, cholesterol and
      phospholipid through the HDL pathway. It is equally relevant that pitavastatin
      therapy has been shown to be efficacious in markedly reducing coronary atheroma
      volume in acute coronary syndrome patients in the JAPAN-ACS trial, a therapeutic
      effect which may be linked to its impact on apoA1/HDL metabolism and function.
      Overall, Phase III and IV studies demonstrate that pitavastatin 1-4 mg is well
      tolerated, attenuates the atherogenic lipid profile and increases LDL-C target
      attainment rates with a similar or greater efficacy to comparable doses of
      atorvastatin, simvastatin and pravastatin. Furthermore, pitavastatin may be
      particularly beneficial in high-risk patients with elevated concentrations of TG
      rich lipoproteins and low levels of HDL-C, and in whom the atheroprotective
      function of HDL particles is typically defective; significantly, such patients
      typically exhibit persistent, residual cardiometabolic risk even when LDL-C is at
      goal. In this context, it is relevant that such patient groups cover a wide
      spectrum of metabolic diseases, including metabolic syndrome, type 2 diabetes,
      coronary disease, familial and non-familial forms of hypercholesterolemia, auto
      immune diseases such as rheumatoid arthritis and lupus, renal disease and some
      forms of hepatic insufficiency.

PMID- 22152283
TI  - Pitavastatin: clinical effects from the LIVES Study.
AB  - Although clinical trials provide useful information on drug safety and efficacy,
      results do not always reflect those observed in the real world. The Japanese long
      term prospective post-marketing surveillance LIVALO Effectiveness and Safety
      (LIVES) Study was designed to assess the efficacy and safety of pitavastatin in
      clinical practice in ~20,000 patients. After 104 weeks, pitavastatin was
      associated with significant reductions in low-density lipoprotein-cholesterol
      (LDL-C) (29.1%) that largely occurred within 4 weeks of treatment initiation. In
      patients with abnormal triglyceride (TG) and high-density lipoprotein-cholesterol
      (HDL-C) levels at baseline, pitavastatin reduced TG and increased HDL-C by 22.7%
      and 19.9%, respectively. Overall, 88.2% of the primary prevention low-risk
      patients attained their Japan Atherosclerosis Society LDL-C target, compared with
      82.7% of intermediate-risk patients, 66.5% of high-risk patients and 50.3% of
      secondary prevention patients. Only 10.4% of pitavastatin-treated patients
      experienced adverse events (AEs), of which approximately 84% were mild and around
      1% was severe. Increases in blood creatine phosphokinase (2.7%), alanine
      aminotransferase (1.8%), myalgia (1.1%), aspartate aminotransferase (1.5%) and
      gamma-glutamyltransferase (1.0%) were the most common AEs and only 7.4% of
      patients discontinued pitavastatin due to AEs. Regression analysis demonstrated
      that age was not a significant factor for the incidence of any AE or myopathy
      associated events. A subanalysis of initial LIVES data focussing on the effects
      of pitavastatin on HDL-C levels showed that HDL-C was elevated by 5.9% in all
      patients and by 24.6% in those with low (<l mmol/L; 40 mg/dL) HDL-C levels at
      baseline (P < 0.0001). A time-course analysis showed that the elevation in HDL-C
      in the low-HDL-C group was enhanced by 14.0% and 24.9% at 12 weeks and 104 weeks,
      respectively. In contrast, previous studies have shown that other statins have
      inconsistent effects on HDL-C levels, with elevations ranging from 0% to 12%.
      According to a LIVES subanalysis, pitavastatin produced a significant increase in
      HDL-C levels in patients switching from other statins, suggesting that patients
      with an unacceptably low level of HDL-C might benefit from switching to
      pitavastatin. Further analyses showed an improvement in HbA1c in patients with
      type 2 diabetes after long-term pitavastatin treatment and a significant increase
      in eGRF in patients with chronic kidney disease. Results from the 5-year LIVES
      extension study (N = 6,582) showed that long-term treatment with pitavastatin was
      well tolerated and that the reduction in LDL-C achieved after 104 weeks was
      maintained for the duration of treatment, whereas levels of HDL-C continued to
      rise. Importantly, multivariate analysis of the 5-year data showed that, in
      addition to advanced age (>= 65 years), male gender, hypertension, diabetes, and
      a history of ischemic heart disease, on-treatment levels of HDL-C and LDL-C were
      significant predictors for cardiovascular (CV) and cerebrovascular risk. In this
      study, the greatest reduction in CV and cerebrovascular risk was achieved by
      patients achieving both their LDL-C and HDL-C targets. Overall, results from the
      LIVES study show that pitavastatin is well tolerated and effectively modifies
      atherogenic lipid profiles, thereby reducing CV and cerebrovascular risk in
      Japanese patients with hypercholesterolemia. Pitavastatin's ability to
      significantly and continually increase HDL-C levels over time suggests a
      particular benefit for patients with low baseline levels of HDL-C and/or those
      that fail to increase their HDL-C levels using alternative statins.

PMID- 22152284
TI  - Secondary amenorrhea in a woman with spinocerebellar degeneration treated with
      thyrotropin-releasing hormone: a case report and in vitro analysis.
AB  - INTRODUCTION: While thyrotropin-releasing hormone is known to be a prolactin
      release stimulating factor, thyrotropin-releasing hormone-tartrate and its
      derivative, taltirelin hydrate, are used for the treatment of spinocerebellar
      degeneration, a degenerative disease characterized mainly by motor ataxia. We
      report the case of a patient being treated with a thyrotropin-releasing hormone
      preparation for spinocerebellar degeneration who developed amenorrhea after a
      dose increase. Her hormonal background was analyzed and the effect of prolonged
      exposure to thyrotropin-releasing hormone on pituitary prolactin-producing cells
      was examined in vitro. CASE PRESENTATION: Our patient was a 36-year-old Japanese
      woman who experienced worsening of gait disturbance at around 23 years of age,
      and was subsequently diagnosed as having spinocerebellar degeneration. She had
      been treated with thyrotropin-releasing hormone-tartrate for four years.
      Taltirelin hydrate was added to the treatment seven months prior to her
      presentation, followed by an improvement in gait disturbance. Around the same
      period, she started lactating and subsequently developed amenorrhea three months
      later. Taltirelin hydrate was discontinued and she was referred to our hospital.
      She was found to have normal sex hormone levels. A thyrotropin-releasing hormone
      provocation test showed a normal response of thyroid-stimulating hormone level
      and an over-response of prolactin at 30 minutes (142.7 ng/mL). Resumption of
      menstruation was noted three months after dose reduction of thyrotropin-releasing
      hormone. In our in vitro study, following long-term exposure to thyrotropin
      releasing hormone, cells from the rat pituitary prolactin-producing cell line GH3
      exhibited an increased basal prolactin promoter activity but showed a marked
      decrease in responsiveness to thyrotropin-releasing hormone. CONCLUSIONS:
      Physicians should be aware of hyperprolactinemia-associated side effects in
      patients receiving thyrotropin-releasing hormone treatment. Long-term treatment
      with a thyrotropin-releasing hormone preparation might cause a large amount of
      prolactin to accumulate in prolactin-producing cells and be released in response
      to exogenous thyrotropin-releasing hormone stimulation.

PMID- 22152285
TI  - Significance of genomic instability in breast cancer in atomic bomb survivors:
      analysis of microarray-comparative genomic hybridization.
AB  - BACKGROUND: It has been postulated that ionizing radiation induces breast cancers
      among atomic bomb (A-bomb) survivors. We have reported a higher incidence of HER2
      and C-MYC oncogene amplification in breast cancers from A-bomb survivors. The
      purpose of this study was to clarify the effect of A-bomb radiation exposure on
      genomic instability (GIN), which is an important hallmark of carcinogenesis, in
      archival formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer by
      using microarray-comparative genomic hybridization (aCGH). METHODS: Tumor DNA was
      extracted from FFPE tissues of invasive ductal cancers from 15 survivors who were
      exposed at 1.5 km or less from the hypocenter and 13 calendar year-matched non
      exposed patients followed by aCGH analysis using a high-density oligonucleotide
      microarray. The total length of copy number aberrations (CNA) was used as an
      indicator of GIN, and correlation with clinicopathological factors were
      statistically tested. RESULTS: The mean of the derivative log ratio spread
      (DLRSpread), which estimates the noise by calculating the spread of log ratio
      differences between consecutive probes for all chromosomes, was 0.54 (range, 0.26
      to 1.05). The concordance of results between aCGH and fluorescence in situ
      hybridization (FISH) for HER2 gene amplification was 88%. The incidence of HER2
      amplification and histological grade was significantly higher in the A-bomb
      survivors than control group (P = 0.04, respectively). The total length of CNA
      tended to be larger in the A-bomb survivors (P = 0.15). Correlation analysis of
      CNA and clinicopathological factors revealed that DLRSpread was negatively
      correlated with that significantly (P = 0.034, r = -0.40). Multivariate analysis
      with covariance revealed that the exposure to A-bomb was a significant (P =
      0.005) independent factor which was associated with larger total length of CNA of
      breast cancers. CONCLUSIONS: Thus, archival FFPE tissues from A-bomb survivors
      are useful for genome-wide aCGH analysis. Our results suggested that A-bomb
      radiation may affect the increased amount of CNA as a hallmark of GIN and,
      subsequently, be associated with a higher histologic grade in breast cancer found
      in A-bomb survivors.

PMID- 22152286
TI  - [The complement system in the pathogenesis of antineutrophil cytoplasm antibodies
      associated vasculitis].
AB  - One of the main characteristics of the vasculitis associated with antineutrophil
      cytoplasm autoantibodies (AASV) is the absence of immune complex deposition in
      biopsies of affected tissues as well as a lack of complement depletion. However,
      in early stages of disease induced in animal models, it has been observed that
      the complement system may be involved in the generation of these diseases. There
      are various animal models which have been developed with the aim of knowing which
      are the pathogenic mechanisms in granulomatosis with polyangiitis (Wegener) (GPA)
      and microscopic polyangiitis (MPA), the latter being explained using these
      approaches in a more satisfactory manner, as there is lack of a model which
      reproduces the changes leading to a granulomatous vasculitis associated with
      antibodies against proteinase-3, as in GPA. This short review presents recent
      evidence of the presence of complement in biopsies of patients with AASV and the
      most recent animal models, which show the participation of complement in their
      etiology.

PMID- 22152287
TI  - [Treatment of large vessel vasculitis].
AB  - Large vessels vasculitis: Giant cells arteritis (GCA), and Takayasu's arteritis
      (TA) are a pair of systemic chronic inflammatory diseases characterized by
      specific involvement of large caliber, elastic-layered arteries. Presently, and
      derived from the paucity of clinical controlled trials approaching the issue, the
      management of GCA and TA is largely based on the clinical judgment of the
      treating physician. Glucocorticoids and immunosuppressive drugs are used when
      clear evidence of inflammatory activity is observed. The traditional management
      approach is to start with systemic glucocorticoid therapy at immunosuppressive
      dose, followed by cytotoxic immunosuppressive drugs (methotrexate, azatioprine,
      cyclophosphamide or mycofenolate mofetil) aimed at maintaining remission and
      decreasing corticosteroid therapy time. Recently, based on the potential
      pathogenic role of tumor necrosis factor alpha in these diseases, a series of
      reports addressing the benefic effect of alphaTNF-blockers in patients who have
      been resistant to the traditional management approach have been published. Non-
      reversible vascular lesions (such as occlusion or stenosis) may require surgical
      treatment (stent or bypass), however this must be done only when a complete
      control of the inflammatory activity has been reached.

PMID- 22152288
TI  - [Biologic therapies in the systemic vasculitides].
AB  - Several biological therapies have been evaluated in systemic vasculitis. Anti TNF
      alpha agents may have a role in the treatment of Takayasu's arteritis and
      probably in giant cell arteritis. In Kawasaki's disease, infliximab is an option
      in subjects with intravenous immunoglobulin-resistant disease. Anti TNF-alpha
      cannot be recommended to treat ANCA-associated vasculitis. Anti-T lymphocyte
      globulin and alemtuzumab could have a role in the treatment of ANCA associated
      vasculitis, although current information about these two biological treatments
      comes from conventional resistant treatment cases, so the high incidence of
      complications and relapses observed with these treatment may be intrinsic to the
      severity of the disease and not related to the biological agents.

PMID- 22152289
TI  - Beverage intake and obesity in Australian children.
AB  - BACKGROUND: There have been increases in the obesity and overweight rates in
      Australian children over the past 25 years and it has been suggested that sugar
      sweetened beverages (SSB) have played a role in this increase. OBJECTIVE: The
      objectives of this study were to: (1) examine SSB intakes in the 2007 Australian
      Children's Nutrition and Physical Activity Survey (2) relate SSB intake to rates
      of overweight and obesity, socio-economic status (SES), TV viewing time, and
      activity levels and (3) compare 2007 SSB intakes with data from the 1995 National
      Nutrition Survey. DESIGN: A computer assisted 24 h dietary recall in 4,400
      children aged 2-16 years was performed. RESULTS: In the 2007 survey 47% of all
      children reported drinking SSBs with 25% consuming sugar sweetened soft drinks on
      the day of the survey. The mean consumption of soft drink was 436 g/d/consumer.
      Activity levels were unrelated to SSB consumption. Television viewing was
      positively related to soft drink consumption with a difference of 55 g/day from
      bottom to top tertile of time spent TV viewing (p = 0.015) in children aged 9-16
      years. 55% of SSB consumption occurred at home and 10% occurred at school. Lower
      SES status was associated with a greater prevalence of SSB consumption- 30% for
      the lowest SES quartile vs 19% in the highest quartile. The proportion of
      overweight who consumed SSBs (which excludes 100% fruit) was not different from
      the non-overweight children although the proportion of SSB consumers in the 6% of
      children who were obese was significant compared with the non-overweight children
      (59% vs 47%, p < 0.05). In the 2007 survey 23% of children were overweight (17%)
      or obese (6%) while in the 1995 survey this figure was 21%. The proportion of
      children consuming SSBs in 1995 and 2007 for selected age groups were: 2-3 years 
      25.8% and 12.8% respectively and 4-7 years - 33.6% and 20.5% respectively (p <
      0.001 for both). CONCLUSIONS: This cross-sectional data set provides evidence
      that SSB consumption for Australian children is still high despite the decrease
      since 1995 in some age groups. It provides little support to conclude that
      overweight in children is currently being driven by excessive SSB consumption
      although it may be factor in some obese children. Conclusions are limited by the
      cross sectional nature of the study.

PMID- 22152290
TI  - Polymicrobial respiratory disease in pigs.
AB  - Respiratory disease in pigs is common in modern pork production worldwide and is
      often referred to as porcine respiratory disease complex (PRDC). PRDC is
      polymicrobial in nature, and results from infection with various combinations of
      primary and secondary respiratory pathogens. As a true multifactorial disease,
      environmental conditions, population size, management strategies and pig-specific
      factors such as age and genetics also play critical roles in the outcome of PRDC.
      While non-infectious factors are important in the initiation and outcome of cases
      of PRDC, the focus of this review is on infectious factors only. There are a
      variety of viral and bacterial pathogens commonly associated with PRDC including
      porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza
      virus (SIV), porcine circovirus type 2 (PCV2), Mycoplasma hyopneumoniae (MHYO)
      and Pasteurella multocida (PMULT). The pathogenesis of viral respiratory disease
      is typically associated with destruction of the mucocilliary apparatus and with
      interference and decrease of the function of pulmonary alveolar and intravascular
      macrophages. Bacterial pathogens often contribute to PRDC by activation of
      inflammation via enhanced cytokine responses. With recent advancements in
      pathogen detection methods, the importance of polymicrobial disease has become
      more evident, and identification of interactions of pathogens and their
      mechanisms of disease potentiation has become a topic of great interest. For
      example, combined infection of pigs with typically low pathogenic organisms like
      PCV2 and MHYO results in severe respiratory disease. Although the body of
      knowledge has advanced substantially in the last 15 years, much more needs to be
      learned about the pathogenesis and best practices for control of swine
      respiratory disease outbreaks caused by concurrent infection of two or more
      pathogens. This review discusses the latest findings on polymicrobial respiratory
      disease in pigs.

PMID- 22152291
TI  - Interaction between innate immunity and porcine reproductive and respiratory
      syndrome virus.
AB  - Innate immunity provides frontline antiviral protection and bridges adaptive
      immunity against virus infections. However, viruses can evade innate immune
      surveillance potentially causing chronic infections that may lead to pandemic
      diseases. Porcine reproductive and respiratory syndrome virus (PRRSV) is an
      example of an animal virus that has developed diverse mechanisms to evade porcine
      antiviral immune responses. Two decades after its discovery, PRRSV is still one
      of the most globally devastating viruses threatening the swine industry. In this
      review, we discuss the molecular and cellular composition of the mammalian innate
      antiviral immune system with emphasis on the porcine system. In particular, we
      focus on the interaction between PRRSV and porcine innate immunity at cellular
      and molecular levels. Strategies for targeting innate immune components and other
      host metabolic factors to induce ideal anti-PRRSV protection are also discussed.

PMID- 22152292
TI  - Detection of O antigens in Escherichia coli.
AB  - Lipopolysaccharide on the surface of Escherichia coli constitutes the O antigens
      which are important virulence factors that are targets of both the innate and
      adaptive immune systems and play a major role in host-pathogen interactions. O
      antigens are responsible for antigenic specificity of the strain and determine
      the O serogroup. The designation of O serogroups is important for classifying E.
      coli strains, for epidemiological studies, in tracing the source of outbreaks of
      gastrointestinal or other illness, and for linking the source to the infection.
      For conventional serogroup identification, serotyping by agglutination reactions
      against antisera developed for each of the O serogroups has been used. In the
      last decade, many O-antigen gene clusters that encode for the enzymes responsible
      for the synthesis of the variable oligosaccharide region on the surface of the
      bacteria have been sequenced and characterized. Unique gene sequences within the
      O-antigen gene clusters have been targeted for identification and detection of
      many O groups using the polymerase chain reaction and microarrays. This review
      summarizes current knowledge on the DNA sequences of the O-antigen gene clusters,
      genetic-based methods for O-group determination and detection of pathogenic E.
      coli based on O-antigen and virulence gene detection, and provides perspectives
      on future developments in the field.

PMID- 22152293
TI  - Escherichia coli O157:H7 in beef cattle: on farm contamination and pre-slaughter
      control methods.
AB  - This paper addresses food safety in beef cattle production, with particular
      emphasis on factors that affect the prevalence of Escherichia coli O157:H7 in
      beef cattle and on control methods that have been investigated. Product recalls
      and foodborne diseases due to this organism continue to occur even though control
      measures have been under investigation for over 20 years. Most meatborne
      outbreaks are due to improper food handling practices and consumption of
      undercooked meat. However, the majority of pathogenic bacteria that can spread at
      slaughter by cross-contamination can be traced back to the farm rather than
      originating from the slaughter plant. This would ideally require the adoption of
      rigorous on-farm intervention strategies to mitigate risks at the farm level. On
      farm strategies to control and reduce E. coli O157:H7 at the farm level will
      reduce the risk of carcass contamination at slaughter and processing facilities
      although they will not eliminate E. coli O157:H7. The most successful strategy
      for reducing the risk of contamination of beef and beef products will involve the
      implementation of both pre- and post-harvest measures.

PMID- 22152294
TI  - Epidemiological simulation modeling and spatial analysis for foot-and-mouth
      disease control strategies: a comprehensive review.
AB  - Foot-and-mouth disease (FMD) is one of the most serious transboundary, contagious
      viral diseases of cloven-hoofed livestock, because it can spread rapidly with
      high morbidity rates when introduced into disease-free herds or areas.
      Epidemiological simulation modeling can be developed to study the hypothetical
      spread of FMD and to evaluate potential disease control strategies that can be
      implemented to decrease the impact of an outbreak or to eradicate the virus from
      an area. Spatial analysis, a study of the distributions of events in space, can
      be applied to an area to investigate the spread of animal disease. Hypothetical
      FMD outbreaks can be spatially analyzed to evaluate the effect of the event under
      different control strategies. The main objective of this paper is to review FMD
      related articles on FMD epidemiology, epidemiological simulation modeling and
      spatial analysis with the focus on disease control. This review will contribute
      to the development of models used to simulate FMD outbreaks under various control
      strategies, and to the application of spatial analysis to assess the outcome of
      FMD spread and its control.

PMID- 22152295
TI  - Regulation of myotube formation by the actin-binding factor drebrin.
AB  - BACKGROUND: Myogenic differentiation involves cell-cycle arrest, activation of
      the muscle-specific transcriptome, and elongation, alignment and fusion of
      myoblasts into multinucleated myotubes. This process is controlled by promyogenic
      transcription factors and regulated by signaling pathways in response to
      extracellular cues. The p38 mitogen-activated protein kinase (p38 MAPK) pathway
      promotes the activity of several such transcription factors, including MyoD and
      MEF2, thereby controlling the muscle-specific transcription program. However, few
      p38-regulated genes that play a role in the regulation of myogenesis have been
      identified. METHODS: RNA interference (RNAi), chemical inhibition and
      immunofluorescence approaches were used to assess the role of drebrin in
      differentiation of primary mouse myoblasts and C2C12 cells. RESULTS: In a search
      for p38-regulated genes that promote myogenic differentiation, we identified
      Dbn1, which encodes the actin-binding protein drebrin. Drebrin is an F-actin side
      binding protein that remodels actin to facilitate the change of filopodia into
      dendritic spines during synaptogenesis in developing neurons. Dbn1 mRNA and
      protein are induced during differentiation of primary mouse and C2C12 myoblasts,
      and induction is substantially reduced by the p38 MAPK inhibitor SB203580.
      Primary myoblasts and C2C12 cells depleted of drebrin by RNAi display reduced
      levels of myogenin and myosin heavy chain and form multinucleated myotubes very
      inefficiently. Treatment of myoblasts with BTP2, a small-molecule inhibitor of
      drebrin, produces a phenotype similar to that produced by knockdown of drebrin,
      and the inhibitory effects of BTP2 are rescued by expression of a mutant form of
      drebrin that is unable to bind BTP2. Drebrin in myoblasts is enriched in cellular
      projections and cell cortices and at regions of cell-cell contact, all sites
      where F-actin, too, was concentrated. CONCLUSIONS: Our findings reveal that Dbn1
      expression is a target of p38 MAPK signaling during myogenesis and that drebrin
      promotes myoblast differentiation.

PMID- 22152297
TI  - Species differences in the effects of bezafibrate as a potential treatment of
      mitochondrial disorders.

PMID- 22152296
TI  - Pseudoaneurysm of the left ventricle following apical approach TAVI.
AB  - Symptomatic severe aortic stenosis carries a two year survival of only 50%.
      However many patients are unsuitable for conventional aortic valve replacement as
      they are considered too high risk due to significant co-morbidities.
      Transcatheter Aortic Valve Implantation (TAVI) offers a viable alternative for
      this high risk patient group, either by the femoral or apical route. This article
      reports a case of a pseudoaneurysm of the left ventricle following an apical
      approach TAVI in an elderly lady with severe aortic stenosis. To our knowledge
      pseduoaneuryms of the left ventricle have been reported infrequently in the
      literature and has yet to be established as a recognised complication of TAVI.

PMID- 22152299
TI  - Seeing the light: probing ROS in vivo using redox GFP.
AB  - Reactive oxygen species (ROS) dictate biological outcomes and are linked with
      myriad pathologies. However, measuring ROS in vivo remains a major obstacle in
      the field. Here, Albrecht et al. (2011) demonstrate the efficacy of redox
      sensitive GFP in measuring glutathione redox state and H(2)O(2) levels of tissues
      in Drosophila.

PMID- 22152300
TI  - Of mice and men: not ExAKTly the same?
AB  - The serine-threonine protein kinase Akt2, also known as PKBbeta, has been shown
      to regulate glucose and lipid metabolism in animal models. In a recent study
      published in Science, Hussain et al. (2011) report that in human subjects an
      activating mutation of Akt2 leads to hypoglycemia and, unexpectedly, asymmetric
      overgrowth.

PMID- 22152301
TI  - Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation.
AB  - The energy requirements of the brain are very high, and tight regulatory
      mechanisms operate to ensure adequate spatial and temporal delivery of energy
      substrates in register with neuronal activity. Astrocytes-a type of glial cell
      have emerged as active players in brain energy delivery, production, utilization,
      and storage. Our understanding of neuroenergetics is rapidly evolving from a
      "neurocentric" view to a more integrated picture involving an intense
      cooperativity between astrocytes and neurons. This review focuses on the cellular
      aspects of brain energy metabolism, with a particular emphasis on the metabolic
      interactions between neurons and astrocytes.

PMID- 22152302
TI  - Identifying novel transcriptional components controlling energy metabolism.
AB  - The investigation of metabolic regulation at the transcriptional level presents
      different challenges than those encountered in the study of other important
      problems like development or cancer. Levels of key components like glucose,
      insulin, and lipids can be modulated but rarely change in an all-or-none fashion,
      necessitating quantitative techniques that can be applied to multiple tissues and
      systems. This review examines recent advances in methods for studying
      transcriptional regulation, with special emphasis on metabolic science. We
      compare these methods for investigators trying to decide on the best approach for
      their particular physiological paradigm or model system.

PMID- 22152303
TI  - TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and
      lipid loading.
AB  - The G protein-coupled receptor TGR5 has been identified as an important component
      of the bile acid signaling network, and its activation has been linked to
      enhanced energy expenditure and improved glycemic control. Here, we demonstrate
      that activation of TGR5 in macrophages by 6alpha-ethyl-23(S)-methylcholic acid (6
      EMCA, INT-777), a semisynthetic BA, inhibits proinflammatory cytokine production,
      an effect mediated by TGR5-induced cAMP signaling and subsequent NF-kappaB
      inhibition. TGR5 activation attenuated atherosclerosis in Ldlr(-/-)Tgr5(+/+) mice
      but not in Ldlr(-/-)Tgr5(-/-) double-knockout mice. The inhibition of lesion
      formation was associated with decreased intraplaque inflammation and less plaque
      macrophage content. Furthermore, Ldlr(-/-) animals transplanted with Tgr5(-/-)
      bone marrow did not show an inhibition of atherosclerosis by INT-777, further
      establishing an important role of leukocytes in INT-777-mediated inhibition of
      vascular lesion formation. Taken together, these data attribute a significant
      immune modulating function to TGR5 activation in the prevention of
      atherosclerosis, an important facet of the metabolic syndrome.

PMID- 22152304
TI  - Impairment of central leptin-mediated PI3K signaling manifested as hepatic
      steatosis independent of hyperphagia and obesity.
AB  - Hepatic steatosis is generally thought to develop via peripheral mechanisms
      associated with obesity. We show that chronic central infusion of leptin
      suppresses hepatic lipogenic gene expression and reduces triglyceride content via
      stimulation of hepatic sympathetic activity. This leptin function is independent
      of feeding and body weight but requires phosphatidylinositol 3-kinase (PI3K)
      signaling. Attenuation of leptin-induced PI3K signaling, brought about by
      transgenic expression of phosphatase and tensin homolog (PTEN) in leptin receptor
      neurons, leads to decreased hepatic sympathetic tone and increased triglyceride
      levels without affecting adiposity or hepatic insulin signaling. Central leptin's
      effects on hepatic norepinephrine levels and triglyceride content are blunted in
      these mutant mice. Simultaneous downregulation of PI3K and signal transducer and
      activator of transcription-3 (Stat3) in leptin receptor neurons does not
      exacerbate obesity but causes more severe hepatic steatosis. Together, our
      results indicate that central cellular leptin resistance in PI3K signaling
      manifests as hepatic steatosis without causing obesity.

PMID- 22152305
TI  - Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with
      nonalcoholic fatty liver disease.
AB  - Approximately one-third of the U.S. population has nonalcoholic fatty liver
      disease (NAFLD), a condition closely associated with insulin resistance and
      increased risk of liver injury. Dysregulated mitochondrial metabolism is central
      in these disorders, but the manner and degree of dysregulation are disputed. This
      study tested whether humans with NAFLD have abnormal in vivo hepatic
      mitochondrial metabolism. Subjects with low (3.0%) and high (17%) intrahepatic
      triglyceride (IHTG) were studied using (2)H and (13)C tracers to evaluate
      systemic lipolysis, hepatic glucose production, and mitochondrial pathways (TCA
      cycle, anaplerosis, and ketogenesis). Individuals with NAFLD had 50% higher rates
      of lipolysis and 30% higher rates of gluconeogenesis. There was a positive
      correlation between IHTG content and both mitochondrial oxidative and anaplerotic
      fluxes. These data indicate that mitochondrial oxidative metabolism is ~2-fold
      greater in those with NAFLD, providing a potential link between IHTG content,
      oxidative stress, and liver damage.

PMID- 22152307
TI  - Caregivers' suffix frequencies and suffix acquisition by language impaired, late
      talking, and typically developing children.
AB  - Acquisition of regular inflectional suffixes is an integral part of grammatical
      development in English and delayed acquisition of certain inflectional suffixes
      is a hallmark of language impairment. We investigate the relationship between
      input frequency and grammatical suffix acquisition, analyzing 217 transcripts of
      mother-child (ages 1 ; 11-6 ; 9) conversations from the CHILDES database.
      Maternal suffix frequency correlates with previously reported rank orders of
      acquisition and with child suffix frequency. Percentages of children using a
      suffix are consistent with frequencies in caregiver speech. Although late talkers
      acquire suffixes later than typically developing children, order of acquisition
      is similar across populations. Furthermore, the third person singular and past
      tense verb suffixes, weaknesses for children with language impairment, are less
      frequent in caregiver speech than the plural noun suffix, a relative strength in
      language impairment. Similar findings hold across typical, SLI and late talker
      populations, suggesting that frequency plays a role in suffix acquisition.

PMID- 22152308
TI  - [Molecular targeted therapy strategies for primary liver cancer].

PMID- 22152306
TI  - Heterozygosity for a loss-of-function mutation in GALNT2 improves plasma
      triglyceride clearance in man.
AB  - Genome-wide association studies have identified GALNT2 as a candidate gene in
      lipid metabolism, but it is not known how the encoded enzyme ppGalNAc-T2, which
      contributes to the initiation of mucin-type O-linked glycosylation, mediates this
      effect. In two probands with elevated plasma high-density lipoprotein cholesterol
      and reduced triglycerides, we identified a mutation in GALNT2. It is shown that
      carriers have improved postprandial triglyceride clearance, which is likely
      attributable to attenuated glycosylation of apolipoprotein (apo) C-III, as
      observed in their plasma. This protein inhibits lipoprotein lipase (LPL), which
      hydrolyses plasma triglycerides. We show that an apoC-III-based peptide is a
      substrate for ppGalNAc-T2 while its glycosylation by the mutant enzyme is
      impaired. In addition, neuraminidase treatment of apoC-III which removes the
      sialic acids from its glycan chain decreases its potential to inhibit LPL.
      Combined, these data suggest that ppGalNAc-T2 can affect lipid metabolism through
      apoC-III glycosylation, thereby establishing GALNT2 as a lipid-modifying gene.

PMID- 22152309
TI  - [Selection and optimization of transport vehicles for hepatocellular carcinoma
      targeted gene therapy].

PMID- 22152310
TI  - [Present study on animal models in gene therapy for primary hepatocellular
      carcinoma].

PMID- 22152311
TI  - [Study on the progression of recombinant adenovirus-herpes simplex virus
      thymidine kinase adjuvant for HCC therapy].

PMID- 22152312
TI  - [The effects of stathmin on cell proliferation and tumor-related genes
      expressions in HCCLM3 cells].
AB  - To explore the biological function and possible underlying mechanism of stathmin
      gene during hepatocarcinogenesis. Three pairs of chemically synthesized small
      interfering RNA (siRNA) targeting on stathmin were transfected into HCCLM3 by
      LipofectamineTM 2000. After confirming the interfering effects of stathmin siRNAs
      through reverse transcription PCR and Western blotting, the HCCLM3 cells
      proliferation and apoptosis were detected by cell count kit-8 (CCK-8) and flow
      cytometry analysis, and the expressions of tumor-related genes (c-myc, c-fos,
      p53, etc) were observed by real-time PCR. Stathmin expression was effectively
      inhibited up to 90% by stathmin silencing in HCCLM3 cells (P is less than to
      0.05) . By using CCK8 assay, it was shown that HCCLM3 cells proliferation were
      obviously depressed by 13.04%+/-0.10%, 28.10%+/-0.41% and 37.36%+/-2.15% at the
      time point of 24 h, 48 h and 72 h with the comparison to Mock group (F = 4.21,  P
      is less than to 0.05). The results of flow cytometry demonstrated that the
      percentage of apoptotic cells was increased to 25.11%+/-1.62% in RNAi group,
      compared with 9.20 %+/-0.64 % in Mock group (F = 44.67, P is less than to 0.01).
      The results of real-time PCR showed that oncogenes c-myc and c-fos expressions
      were repressed, proliferation-associated gene ki-67 was down-regulated, and
      apoptosis-promoting gene caspase-3, bax and p53 were induced (P is less than to
      0.05). Stathmin may promote cell proliferation, inhibit cell apoptosis and induce
      malignant transformation of hepatocytes by regulating some tumor-related genes
      expressions.

PMID- 22152313
TI  - [The effect of hepatitis B virus X protein on the expression of CtIP in HepG2
      Cells].
AB  - To investigate the effect of hepatitis B virus X protein(HBx) on CtBP-interacting
      protein(CtIP) which is an important repair factor of DNA double strand break
      damage in HepG2 cells induced by bleomycin. A HBx stably expressing HepG2 cell
      line and a control HepG2 cell line with empty vector transfected were
      established. After the double strand break (DSB) damage occurred, the mRNA and
      protein levels of CtIP were detected by Real-time PCR and Western blot assay
      respectively, cell cycle profiles and apoptotic cell death were determined by a
      flow cytometry, and the position of CtIP in cells was observed by confocal laser
      scanning microscopy. It showed  that HepG2 cells transfected with hepatitis B
      virus X gene could stably express HBx protein. After being induced by bleomycin,
      the percentage of apoptotic cell was 16.90%+/-0.89% in HBx stably expressing
      HepG2 cell line and 15.30%+/-0.86% in control cell line, respectively (q = 2.074,
      P is more than to 0.05). While the percentage of death cell was 8.71%+/-0.74% in
      HBx stably expressing HepG2 cell line and 4.90%+/-0.46% in control cell line,
      respectively (q = 7.126, P is less than to 0.01). The two cell lines manifested
      the increase of G2/M arrest and significant difference existed between the two
      cell lines. HBx down regulated the expression levels of CtIP and its mRNA. The
      CtIP level was 0.66+/-0.04 in HepG2-HBx cell and 0.73+/-0.05 in HepG2-vec cell,
      respectively (t = 2.314, P is less than to 0.05). The relative mRNA level was
      1.00+/-0.06 in HepG2-HBx cell and 1.23+/-0.08 in HepG2-vec cell, respectively (t
      = 2. 732, P is less than to 0.05). We also found that CtIP was concentrated in
      the cell nucleus. The research suggests that HBx may affect DNA-repair pathways
      by disrupting the expression of CtIP.

PMID- 22152314
TI  - [Effect of miR-221 on the viability and apoptosis of hepatocellular carcinoma
      HepG2 cells].
AB  - To investigate the effect of microRNA-221 (miR-221) on cell viability and
      apoptosis of hepatocellular carcinoma HepG2 cells. MiR-221 inhibitors and mimics
      were transfected into HepG2 cells. The expression of miR-221 was detected by real
      time quantitative RT-PCR. CellTiter-blue cell viability kit, Hoechst
      33342/propidium iodide (PI) double staining assay, flow cytometry and Apo-ONE
      homogeneous caspase-3/7 kit were used to measure cell viability and apoptosis.
      MiR-221 inhibitors significantly inhibited the cell growth and miR-221 mimics
      increased cell viability 48 hours post-transfection measured by both CellTiter
      blue cell viability kit and Hoechst 33342/PI assay (P is less than to 0.05).
      There was a positive correlation between these two assays (r = 0.993, P is less
      than to 0.01). With miR-221 mimics, the number of G1 stage cells (47.67%+/-1.53%)
      was significantly reduced as compared to the blank control (59.00%+/-1.00%) and
      the negative control (58.00%+/-1.00%, F = 81.77, P is less than to 0.01), and it
      was significantly raised in S stage (20.33%+/-1.15%) than in blank control
      (11.00%+/-1.00%) and negative control (12.00%+/-1.00%, F = 70.9, P is less than
      to 0.01) with flow cytometry analysis. More cell apoptosis and necrosis were
      significantly induced by miR-221 inhibitors 48 hours post-transfection detected
      by both Hoechst 33342/PI assay and flow cytometry PE Annexin V kit (P is less
      than to 0.05). The result from Apo-ONE homogeneous caspase-3/7 kit was consistent
      with the above two apoptotic assays, which showed that with miR-221 inhibitors,
      the activity of caspase-3/7 was significantly enhanced (P is less than to 0.05).
      MiR-221 contributes to the growth of hepatocellular carcinoma cells and miR-221
      inhibition can induce cell apoptosis. miR-221 has the potential to become one of
      the new molecular targets for liver cancer therapy.

PMID- 22152315
TI  - [Expressions of CD34 and CD117 in human hepatocellular carcinomas and the
      clinical significance].
AB  - To study the expressions of CD34 and CD117 in the tissues of hepatocelluar
      carcinoma (HCC) and to explore the relationship with clinical pathology and it's
      evaluation on the prognosis of HCC patients. The expressions of CD34 and CD117
      were examined by two-step methods of PV-9000 of immunohistochemistry in 55 HCC
      cases, 10 liver cirrhotic specimens and 6 normal liver specimens. Clinical
      pathological data, tumor recurrent rate and survival rate after hepatectomy were
      recorded and analyzed with Fisher's Exact Test, Pearson X2 Test, Kaplan-Meier,
      Log-Rank Test and Cox Regression. The positive expression of CD34 was found in
      65.4% of HCC, 20% of cirrhostic liver specimens and 16.7% of normal liver
      specimens, respectively. Significant differences found among the three groups,
      and the CD34 expression was significantly associated with vessel embolus (X2 =
      4.000, P = 0.046) and the histological grades (X2 = 11.008, P = 0.001). The
      positive expression of CD117 was 47.3%, 10% and 0% in HCC, cirrhotic liver
      specimens and normal liver tissues, respectively, and statistical differences
      esxisted among the three groups. The CD117 expression was dramatically related to
      the histological grades (X2 = 5.115, P = 0.024) and clinical stages (X2 = 15.459,
      P = 0.000). Median disease free survival time after hepatectomy was significantly
      shorter in the group with positive-expression of CD34 (X2 = 4.105, P = 0.043) and
      CD117 (X2 = 28.023, P = 0.000) than the negative-expressed groups, respectively.
      Multivariate analysis showed that CD117 expression status, serum AFP levels and
      the size of tumor were independently prognostic factors for HCC patients. Tthe
      results demonstrated that CD34 and CD117 might play an important role in liver
      carcinogenesis and the progression of HCC, and they might potentially serve as
      markers for HCC prognosis.

PMID- 22152316
TI  - [Investigation on the migration and biologic effects of nano FeOx powders under
      the exposure of extremely low frequency altering electric magnetic field in human
      heptoma-bearing nude mice in vivo].
AB  - To investigate the mechanism and biologic effects of 37 nm magnetic nano FeOx
      powders (MNPs) on human hepatoma-bearing nude mice. 37 nm MNPs were prepared by
      coprecipitation methods and then injected into human hepatoma (Bel-7402) bearing
      nude mice through the tail vein. After injection of MNPs, the mice were first
      exposed under static magnetic field and then treated under extremely low
      frequency altering-electric magnetic field directing to the tumor area. The
      migration and trafficking of MNPs were determined by MMR. Tumor growth was
      monitored with calipers every 5 days and tumor volume was calculated on the basis
      of three-dimensioned measurements. The apoptosis of tumor cells was analyzed by
      flow cytometry analysis. The expressions of apoptosis-associated proteins Bcl-2,
      Bax and HSP27 were determined using western-blot analysis. Static magnetic field
      could direct the migration and trafficking of MNPs to the tumor site with a
      higher ratio of 98.9%. Extremely Low Frequency Electric-Magnetic Field (EMF)
      treatment could inhibit the proliferation of tumor cells and prolong the survive
      time of tumor-bearing mice injected with MNPs. In addition, the survival time of
      tumor-bearing mice and percentages of prohibition on tumor cell growth were
      27.4+/-0.7 days and 37.5+/-0.8% (F = 0.005, P is less than to 0.05),
      respectively. The results of flow cytometry analyses showed that about 18.1+/
      0.6% (F = 0.030, P is less than to 0.05) of tumor cells were induced into early
      apoptosis. Furthermore, expressions of apoptosis-associated proteins Bcl-2 and
      Bax were significantly induced by MNPs under EMF treatment. The ratio of Bcl/Bax
      in both MNPs and EMF treatment group was 0.07+/-0.01, which was much lower than
      that of control group (0.23+/-0.02) (F = 0.016, P is less than to 0.05). Heat
      shock protein-27 (Hsp-27) was not significantly induced in different treatment
      groups. Injection of MNPs with EMF exposure on human hepatoma-bearing nude mice
      could significantly prolong the survival time, inhibit the tumor proliferation
      and growth, and induce tumor cells into apoptosis.

PMID- 22152317
TI  - [Wnt/b-catenin signaling pathway affects the protein expressions of caspase-3,
      XIAP and Grp-78 in hepatocellular carcinoma].
AB  - To investigate the relationship and significance of Wnt/b-catenin signaling
      pathway with caspase-3, XIAP, HSP27and Grp-78. The HCC cell line HepG2 was
      transfected with small interfering RNA (siRNA) directed against b-catenin. After
      72 and 96 h, protein was extracted and the protein expressions of b-catenin,
      caspase-3, XIAP, Grp-78 and HSP27 were detected by Western blot. b-catenin
      protein expression was inhibited at both time points and the expression at 96 h
      was higher than that at 72 h (F = 160.72, P is less than to 0.01). Interestingly,
      Caspase-3 protein expression was decreased at 72 h and increased to normal at 96
      h (F = 136.10, P is less than to 0.01), while p-caspase-3 protein expression
      increased at 72 h and decreased to normal at 96 h (F = 98.65, P is less than to
      0.01). XIAP protein expression decreased at 72 h (F = 37.29, P is less than to
      0.01) and increased at 96 h. Grp-78 protein expression increased at 72 h and
      decreased to normal at 96 h ( F = 58.72, P is less than to 0.01). HSP27 protein
      expression showed no change following transfection ( F = 1.91, P is more than to
      0.05). Wnt/b-catenin signaling pathway is related to the protein expressions of
      caspase-3, XIAP and Grp-78, but not related to HSP27 protein expression in HCC.
      Wnt/b-catenin signaling pathway may participate in the regulation of HCC
      apoptosis, proliferation and differentiation through affecting these factors.

PMID- 22152318
TI  - [Correlation research of isolated liver tissue pathology and clinical diagnosis
      in patients with chronic severe hepatitis B].
AB  - To study the coincidence rate of clinical diagonisis with pathological diagnosis
      for chronic severe hepatitis, and to screen out clinical indicators consistent
      with pathological diagnosis. Fifty-one patients diagnosed as chronic severe
      hepatitis and underwent liver transplantation in Beijing You'an hospital from
      November 2004 to June 2009 participated in this study. The clinical data were
      selected as following: ALT, AST, urea nitrogen, creatinine, glucose,
      cholinesterase, total cholesterol, Glutamyl endopeptidase, alkaline phosphatase,
      serum potassium, serum sodium, prothrombin activity and blood ammonia level. The
      width of the portal vein and splenic vein thickness were measured by color
      Doppler ultrasound and were compared in different groups. Data were ananlyzed
      with independent sample t test and F test. The coincidence rate between clinical
      and pathological diagnoses in this study was 64.7%. ALT and AST levels for
      Chronic severe hepatitis and decompensated cirrhosis were 675.0+/-510.0 U/L,
      67.00+/-45.0 U/L ( P is less than to 0.01) and 392.0 +/-370.0 U/L, 103.0+/-59.0
      U/L (P is less than to 0.01) respectively, with statistically significant
      difference existed. The mean level of ALT in Chronic severe hepatitis group was
      significantly different in the situations of onset less than 30 days or more than
      30 days (means were 761.0+/-743.0 U/L and 117.0+/-112.0 U/L, P is less than to
      0.01). The rate of the phenomenon of enzyme isolated bile in the chronic severe
      hepatitis and decompensated cirrhosis group were 78.9% and 0 respectively. The
      coincidence rate of clinical with pathological diagnoses for Chronic Severe
      Hepatitis was low, increased ALT and AST levels would help improve the diagnostic
      accuracy.

PMID- 22152319
TI  - [Effect of HBV on the expression of SREBP in the hepatocyte of chronic hepatitis
      B patients combined with hepatic fatty change].
AB  - To investigate the effect of HBV on the expression of Sterol regulatory element
      binding proteins( SREBP ) in the hepatocyte of patients with chronic hepatitis B
      (CHB) combined with hepatic fatty change. 55 cases diagnosed as CHB combined with
      hepatic fatty change in our department were selected and liver biopsies were
      carried out. The patients were dividied into 3 groups, group A: HBV DNA is less
      than or equal to 1000 copies/ml(15 cases), group B: 1000 copies/ml less than HBV
      DNA less than 100000 copies/ml (18 cases) and group C: HBV DNA is more than or
      equal to 100000 copies/ml (22 cases). 10 patients with HBV DNA in less than or
      equal to 1000 copies/ml after antiviral therapy with Nucleoside analogues were
      seen as group C1 (before treatment) and group C2 (after treatment) respectively;
      12 patients with HBV DNA is more than or equal to 100000 copies/ml after
      antiviral therapy were classified as group C3 (before treatment) and group C4
      (after treatment). Lipid droplets in the hepatic tissue were observed with oil
      red staining. Real time PCR were performed to detect the expressions of SREBP-1c
      and SREBP-2 mRNA in the liver. The protein expressions of SREBP-1c and SREBP-2
      were detected with immunohistochemistry staining. Statistic data were analysed
      with SPSS11.5 software. (1) Red integrated optical densities (IOD) reflected by
      lipid drops in group A, B and C are 1004.27+/-218.63, 1937.01+/-401.47 and
      4133.79+/-389.28 respectively, the degree of oil red O in each group was
      different (F = 385.69, P is less than to 0.01), which is increased as HBV DNA
      load increasing; Red IOD in group C1, C2 and C3, C4 are 4020.84+/-326.64,
      1012.02+/-244.89, 4189.18+/-329.21 and 4121.76+/-304.09 respectively. Compared
      with group C1, the degree of oil red O in group C2 is decreased and the
      difference is statistically significant (t = 22.55, P is less than to 0.01);
      However, the difference of the degree of oil red O between group C4 and C3 is not
      statistically significant. (2) Compared with group A, the expressions of SREBP-1c
      mRNA in group B and C are raised by 1.218+/-0.130 and 1.798+/-0.118 times
      respectively, among group A, B, C, the expressions of SREBP-1c mRNA are
      statistically significant different ( F = 297.47, P is less than to 0.01). The
      expressions of SREBP-2 mRNA in group B and C are decreased  by 0.956+/-0.118 and
      0.972+/-0.153 times as compared to group A. However, the difference of SREBP-2
      mRNA expression among the 3 groups is not statistically significant ( F = 0.568,
      P is more than to 0.05). Compared with group C1, SREBP-1c mRNA in group C2 is
      decreased by 0.714+/-0.081 folds (t=11.224, P is less than to 0.01), while SREBP
      2 mRNA in group C2 is raised by1.034+/-0.155 times(t=0.692, P is more than to
      0.05). SREBP-1c mRNA and SREBP-2 mRNA in group C4 are raised by 1.012+/-0.206
      times and  decreased by 0.998+/-0.183 times as compared to group C3 without
      difference found (t=0.196 or 0.031, P is more than to 0.05). (3) the expressions
      of SREBP-1c protein in group A, B and C are 36257.21+/-5709.79, 50413.47+/
      4989.28 and 71025.83+/-6047.13 respectively, and the difference is statistically
      significant among the 3 groups (F = 178.26, P is less than to 0.01); the
      expressions of SREBP-2 protein in group A, B and C are 32913.52+/-3951.21,
      32625.91+/-4025.06 and 34173.44+/-5316.25 respectively, but the difference is not
      statistically significant among the 3 groups ( F = 0.562, P is more than to
      0.05), SREBP-1c protein levels in group C1, C2, C3, C4 are 69832.16+/-4941.36,
      48735.47+/-5471.41, 70871.69+/-5083.14 and 68913.32+/-5343.22 respectively, the
      difference of SREBP-1c protein levels between group C1 and C2 is statistically
      significant (t=10.260, P is less than to 0.01); while the difference between
      group C3 and group C4 is not statistically significant(t=1.558, P is more than to
      0.05). The expressions of SREBP-2 protein in group C1, C2, C3 and C4 are 33
      980.21+/-4081.80, 34011.50+/-3859.27, 33610.12+/-4761.10 and 32915.66+/-5023.61
      respectively, the difference of SREBP-2 protein levels in group C1 and group C2
      is not statistically significant (t=0.038, P is more than to 0.05) and same
      result exists between group C3 and group C4 (t=0.459, P is more than to 0.05).
      HBV DNA may participate in the hepatic steatosis formation through interfering
      with the SREBP-1c expression.

PMID- 22152320
TI  - [Effects of telmisartan on nonalcoholic steatohepatitis rat model by activating
      peroxisome proliferator-activated receptor r].
AB  - To investigate the effects of telmisartan on steatohepatitis (NASH) in rats by
      activating peroxisome proliferator-activated receptor gamma (r). Thirty male SD
      rats were randomized into normal control group, NASH control group and
      telmisartan prevention group. Normal control group was given standard food and
      the other two groups were given high fat diet for 16 weeks to induce NASH.
      Prevention group was given telmisartan (5 mg.kg-1.d-1) for 4 weeks by
      intragastric adminstration after 12 weeks. At the end of the 16th week, all the
      rats were sacrificed. Pathological changes of liver were observed by optical
      microscopy. Serum alanine aminotransferase(ALT), aspartate aminotransferase(AST),
      fasting blood glucose(FBG), fasting insulin(FINS), HOMA-IR(homeostasis model
      assessment insulin resistance), Serum TNF-a and adiponectin were detected and
      analyzed.Western blot and RT-PCR were used to detect PPARr expression in hepatic
      tissues on protein and mRNA levels. (1) Rats were successfully modeled. The liver
      tissue samples were divided into 4 degrees (F0 - 4) based on total fatty
      degeneration of liver cells.There was one rat reached F3 and nine rats reached F4
      in NASH group, one rat reached F1, six rats reached F2 and three rats reached F3
      in prevention group. Inflammatory activity scores of hepatic tissues in the model
      group were 2.67+/-0.25, while that in the control group was 0 (U=15 and P is less
      than to 0.01), in the prevention group were 2.67+/-0.25 and 1.36+/-0.12 (U=24 and
      P is less than to 0.05 ). (2) The levels of serum ALT, AST, FBG, FINS, TNFa and
      HOMA-IR in the model group were increased than those in the control group( the
      vaules of q were 13.130, 6.472, 6.909, 26.619, 14.591 and 49.683 respectively, P
      less than 0.01). The levels of serum ALT, FINS, FBG, TNFa and HOMA-IR in the
      prevention group were decreased as compared to the model group (the vaules of q
      were 7.024, 4.145, 14.829, 13.195 and 31.991 respectively, P less than 0.01 ).
      (3) The serum adiponectin, PPARrmRNA and protein in liver tissues of the model
      group were lower than those in the control group (q values were 10.696, 8.679 and
      16.762 respectively, P is less than to 0.05).The data in the prevention group
      were higher as compared to the model group(q values were 3.879,3.079,6.400, P is
      less than to 0.05 respectively). HOMA-IR was positively correlated with the
      expression of TNFa but negatively correlated with the expression of adiponectin
      (r = 0.927, P is less than to 0.01; r = -0.891, P is less than to 0.01,
      respectively). Telmisartan may has preventive effect on rats with steatohepatitis
      (NASH)  by a mechanism of activating peroxisome proliferator-activated receptor
      r.

PMID- 22152321
TI  - [Risk factors for spontaneous bacterial peritonitis in cirrhotic patients with
      ascites].

PMID- 22152322
TI  - [Effect of Benazepril on the expression of ACE2 in rats with hepatic fibrosis].

PMID- 22152323
TI  - [Human amniotic epithelial cells can differentiate into hepatocyte -like cells].

PMID- 22152324
TI  - [Regulation of hepatitis B virus X protein on the expression of HSP90a gene in
      human hepatocarcinoma cells].

PMID- 22152325
TI  - [Pegasys and ribavirin therapy in an elderly patient with chronic hepatitis C].

PMID- 22152326
TI  - [3 cases with idiopathic portal hypertension: a review of literature].

PMID- 22152327
TI  - [Application of glucocorticosteroids in severe alcoholic hepatitis].

PMID- 22152328
TI  - [Antituberculosis drug -induced liver damage].

PMID- 22152329
TI  - [Clinical significance of quantitative assay of hepatitis B surface antigen].

PMID- 22152331
TI  - Molecular identification of Austrobilharzia species parasitizing Cerithidea
      cingulata (Gastropoda: Potamididae) from Kuwait Bay.
AB  - Avian schistosomes belonging to the genus Austrobilharzia (Digenea:
      Schistosomatidae) are among the causative agents of cercarial dermatitis in
      humans. In this paper, ribosomal and mitochondrial DNA sequences were used to
      study schistosome cercariae from Kuwait Bay that have been identified
      morphologically as Austrobilharzia sp. Sequence comparison of the ribosomal DNA
      (rDNA) 28S and 18S regions of the collected schistosome cercariae with
      corresponding sequences of other schistosomes in GenBank revealed high sequence
      similarity. This confirmed the morphological identification of schistosome
      cercariae from Kuwait Bay as belonging to the genus Austrobilharzia. The finding
      was further supported by the phylogenetic tree that was constructed based on the
      combined data set 18S-28S-mitochondrial cytochrome oxidase I (mtCO1) sequences in
      which Austrobilharzia sp. clustered with A. terrigalensis and A. variglandis.
      Sequence comparison of the Austrobilharzia sp. from Kuwait Bay with A.
      variglandis and A. terrigalensis based on mtCO1 showed a variation of 10% and
      11%, respectively. Since the sequence variation in the mtCO1 was within the
      interspecific range among trematodes, it seems that the Austrobilharzia species
      from Kuwait Bay is different from the two species reported in GenBank, A.
      terrigalensis and A. variglandis.

PMID- 22152333
TI  - Evaluating an integrated neighbourhood approach to improve well-being of frail
      elderly in a Dutch community: a study protocol.
AB  - BACKGROUND: An important condition for independent living is having a well
      functioning social network to provide support. An Integrated Neighbourhood
      Approach (INA) creates a supportive environment for the frail elderly, offering
      them tailored care in their local context that allows them to improve self
      management abilities and well-being. The purpose of our research is to
      investigate how an INA can contribute to outcomes of frail elderly and the cost
      effectiveness of such a program. The first central study question is: To what
      extent does INA contribute to (a) continuous, demand-driven, coordinated care and
      support for the independently- living frail elderly; (b) improvement of their
      well-being and self-management abilities; and (c) reinforcement of their
      neighbourhood networks. The second central research question is: is the INA a
      cost-effective method to support the frail, independently- living elderly?
      METHODS: We investigate a Dutch INA. This transition experiment aims to
      facilitate the independently-living frail elderly (70+) to live the life they
      wish to live and improve their well-being. The study population consists of
      independently-living frail elderly persons in Rotterdam. The transition
      experiment starts in two Rotterdam districts and is later extended to two other
      districts. We propose a concurrent mixed methods design, that is, a combination
      of qualitative and quantitative research methods to evaluate processes, effects
      and costs of INA. Such a design will provide insight into an on-going INA and
      demonstrate which of its elements are potentially (cost)-effective for the frail
      elderly. DISCUSSION: We embrace a wide range of scientific methodologies to
      evaluate the INA project and obtain information on mechanisms and contexts that
      will be valuable for decision making on local and national levels. The study will
      lead to a better understanding of how to provide support via social networks for
      the frail elderly and add to the knowledge on the feasibility and cost
      effectiveness of the program in maintaining or improving their well-being. Last,
      the study will highlight the factors that determine the program's success or
      failure.

PMID- 22152334
TI  - 18th Pediatric Rheumatology European Society (PReS) Congress Bruges, Belgium.  14
      18 September 2011. Abstracts.

PMID- 22152332
TI  - Vitamin D deficiency is associated with mortality in the medical intensive care
      unit.
AB  - INTRODUCTION: The incidence of vitamin D deficiency in critically ill patients
      has been reported to range from as low as 17% to as high as 79%. Data regarding
      the relationship between 25-hydroxyvitamin D levels and outcomes in the medical
      intensive care unit are sparse. The goal of the study was to evaluate the
      prevalence of 25-hydroxyvitamin D deficiency in the medical intensive care unit
      and its relationship with outcomes. METHOD: This was a retrospective study in a
      medical intensive care unit (MICU) at an inner city community hospital. The study
      period was between October 2009 and February 2010. RESULTS: Of the 932 patients
      admitted during the study period, 25-hydroxyvitamin D vitamin D (25(OH)D) levels
      were available in 523 (53%); 86 of them were excluded from the study due to
      readmission to the intensive care unit. Deficiency was defined as 0 to 19.9 ng/dL
      25(OH)D levels, insufficiency as 20 to 29.9 ng/dL, and normal levels as >=30
      ng/dL. Of the 437 patients studied, 25(OH)D deficiency was identified in 340
      (77.8%), insufficiency in 74 (16.9%), and normal levels in 23 (5.3%) patients.
      Patients with 25(OH)D deficiency/insufficiency were younger (P = 0.015), were
      male (P = 0.001), and had kidney disease (P = 0.017) and lower total serum
      calcium levels (P = 0.003). Hospital mortality was higher in patients with
      25(OH)D deficiency (P = 0.01). No differences in ventilator days or length of
      stay in the MICU were evident among the three groups. Analysis by multiple
      logistic regression demonstrated that acute physiology and chronic health
      evaluation (APACHE) IV score ((odds ratio (OR) 1.036; 95% confidence interval
      (CI) 1.024-1.048, P < 0.0001), ventilator requirement (OR 7.7; 95% CI 4.3-13.98,
      P < 0.0001), 25(OH) D levels(OR 0.942; 95% CI 0.942-0.904, P < 0.0005) and 25(OH)
      D deficiency (OR 8.7; 95% CI 1.03-72.8, P < 0.0469) showed statistical
      significance. There was no association between 25(OH)]D insufficiency and
      hospital mortality. The mean 25(OH)D level of survivors (27.9 +/- 9.7 ng/dL) was
      higher than for non-survivors (9.7 +/- 4.7 ng/dL; P < 0.0001). CONCLUSIONS: The
      study results demonstrate an association between 25(OH)D deficiency and hospital
      mortality in MICU patients. A randomized prospective study to evaluate the effect
      of vitamin D replacement therapy on mortality is warranted.

PMID- 22152335
TI  - Bilateral spontaneous retroperitoneal bleeding in a patient on nimesulide: a case
      report.
AB  - INTRODUCTION: Spontaneous retroperitoneal bleeding is a rare but potentially life
      threatening event of varied etiology. Herein we report a case of bilateral non
      traumatic retroperitoneal hemorrhage. CASE PRESENTATION: A 50-year-old Greek man,
      who was on a non-steroidal anti-inflammatory agent (nimesulide) for ankylosing
      spondylitis, presented with a right retroperitoneal hematoma combined with
      contralateral subcapsular renal hematoma. Bleeding on his right side was
      successfully controlled by arterial embolization with coils, whereas the left
      renal hematoma was treated conservatively. His recovery period was uneventful.
      CONCLUSION: This is the first reported case of bilateral retroperitoneal bleeding
      in a patient receiving nimesulide for ankylosing spondylitis. The application of
      minimally invasive techniques resulted in the desired positive outcome with
      preservation of both renal units.

PMID- 22152336
TI  - Noninvasive ventilation outside the intensive care unit from the patient point of
      view: a pilot study.
AB  - BACKGROUND: Noninvasive ventilation (NIV) is increasingly utilized outside the
      ICU for patients with acute respiratory failure. However, success and failure
      risk factors and patient safety aspects have been poorly explored in this
      setting. So far, no study has evaluated the perspective  of the patient, despite
      the known high relevance of patient participation for NIV success. METHODS: We
      prospectively interviewed (following a standard questionnaire) the patients
      successfully treated with NIV for acute respiratory failure outside the ICU.
      Subjects were interviewed 24-48  hours after NIV suspension. EXCLUSION CRITERIA:
      NIV failure, patient not competent, patient unwilling to participate in the
      study, patient transferred to the ICU. RESULTS: Forty-five consecutive patients
      were included in the study. Only 20% participated in the initial setting of NIV
      parameters.  More than 40% reported they never had the possibility to discuss the
      NIV treatment. Eighty percent reported they were never asked to try another
      interface. All subjects knew how to call for help, but only one fourth had been
      trained to remove the mask, and 22% reported not being able at all  to remove the
      mask if needed. One half of the subjects reported having received help
      immediately when needed, but 15% waited more than 3 min. All subjects reported
      complications, and 18% reported respiratory worsening while on NIV. CONCLUSIONS:
      Subjects reported a low level of involvement  in the initial setting of NIV
      treatment, low satisfaction about communication with the caring staff, and a
      suboptimal safety level in case of emergency.

PMID- 22152338
TI  - Cognitive function and assistive technology for cognition: a systematic review.
AB  - The relationship between assistive technology for cognition (ATC) and cognitive
      function was examined using a systematic review. A literature search identified
      89 publications reporting 91 studies of an ATC intervention in a clinical
      population. The WHO International Classification of Functioning, Disability and
      Health (ICF) was used to categorize the cognitive domains being assisted and the
      tasks being performed. Results show that ATC have been used to effectively
      support cognitive functions relating to attention, calculation, emotion,
      experience of self, higher level cognitive functions (planning and time
      management) and memory. The review makes three contributions: (1) It reviews
      existing ATC in terms of cognitive function, thus providing a framework for ATC
      prescription on the basis of a profile of cognitive deficits, (2) it introduces a
      new classification of ATC based on cognitive function, and (3) it identifies
      areas for future ATC research and development.

PMID- 22152337
TI  - Temporal pattern of expression and colocalization of microglia/macrophage
      phenotype markers following brain ischemic injury in mice.
AB  - BACKGROUND: Emerging evidence indicates that, similarly to what happens for
      peripheral macrophages, microglia can express different phenotypes depending on
      microenvironmental signals. In spite of the large literature on inflammation
      after ischemia, information on M/M phenotype marker expression, their
      colocalization and temporal evolution in the injured brain is lacking. The
      present study investigates the presence of microglia/macrophage phenotype
      markers, their temporal expression, whether they are concomitantly expressed by
      the same subpopulation, or they are expressed at distinct phases or locations in
      relation to the ischemic lesion. METHODS: Volume of ischemic lesion, neuronal
      counts and TUNEL staining were assessed in C57Bl/6 mice at 6-12-24-48 h and 7d
      after permanent occlusion of the middle cerebral artery. At the same time points,
      the expression, distribution in the lesioned area, association with a definite
      morphology and coexpression of the microglia/macrophage markers CD11b, CD45,
      CD68, Ym1, CD206 were assessed by immunostaining and confocal microscopy.
      RESULTS: The results show that: 1) the ischemic lesion induces the expression of
      selected microglia/macrophage markers that develop over time, each with a
      specific pattern; 2) each marker has a given localization in the lesioned area
      with no apparent changes during time, with the exception of CD68 that is confined
      in the border zone of the lesion at early times but it greatly increases and
      invades the ischemic core at 7d; 3) while CD68 is expressed in both ramified and
      globular CD11b cells, Ym1 and CD206 are exclusively expressed by globular CD11b
      cells. CONCLUSIONS: These data show that the ischemic lesion is accompanied by
      activation of specific microglia/macrophage phenotype that presents distinctive
      spatial and temporal features. These different states of microglia/macrophages
      reflect the complexity of these cells and their ability to differentiate towards
      a multitude of phenotypes depending on the surrounding micro-environmental
      signals that can change over time. The data presented in this study provide a
      basis for understanding this complex response and for developing strategies
      resulting in promotion of a protective inflammatory phenotype.

PMID- 22152339
TI  - Transcriptome analysis of anti-fatty liver action by Campari tomato using a
      zebrafish diet-induced obesity model.
AB  - BACKGROUND: High dietary intake of vegetable products is beneficial against
      obesity and its related diseases such as dyslipidemia, nonalcoholic fatty liver
      disease, and cancer. We previously developed a diet-induced obesity model of
      zebrafish (DIO-zebrafish) that develops visceral adiposity, dyslipidemia, and
      liver steatosis. Zebrafish is a polyphagous animal; thus we hypothesized that DIO
      zebrafish could be used for transcriptome analysis of anti-obesity effects of
      vegetables. RESULTS: Each vegetable exhibited different effects against obesity.
      We focused on "Campari" tomato, which suppressed increase of body weight, plasma
      TG, and lipid droplets in livers of DIO-zebrafish. Campari tomato decreased
      srebf1 mRNA by increase of foxo1 gene expression, which may depend on high
      contents of beta-carotene in this strain. CONCLUSIONS: Campari tomato ameliorates
      diet-induced obesity, especially dyslipidemia and liver steatosis via
      downregulation of gene expression related to lipogenesis. DIO-zebrafish can
      discriminate the anti-obesity effects of different strains of vegetables, and
      will become a powerful tool to assess outcomes and find novel mechanisms of anti
      obesity effects of natural products.

PMID- 22152340
TI  - Damage index in childhood-onset systemic lupus erythematosus in Egypt.
AB  - BACKGROUND: To investigate the prevalence of cumulative organ damage among
      Egyptian children with juvenile-onset systemic lupus erythematosus (jSLE) and the
      relationships between the organ damage and the demographic data, clinical
      variables, and disease activity. METHODS: A total of 148 patients with jSLE have
      been followed in the pediatric rheumatology clinic and section at Cairo
      University. These patients were evaluated by retrospective chart review. The
      organ system damage due to SLE was measured using the Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage Index
      (SDI). Risk factors for damage were also studied including demographic criteria
      as well as clinical and laboratory manifestations. RESULTS: Overall, 43.9% of the
      patients had damage within a mean of 6.57 +/- 3.59 years of disease diagnosis.
      Neuropsychiatric (NPS-21%) and renal (16.9%) system involvement were observed
      most frequently, followed by cardiovascular (11.5%), skin (9.5%), pulmonary
      (6.1%), and ocular (4.8%), with a mean SDI score of 0.93 +/- 1.37. In our study,
      the presence of neuropsychiatric manifestations at diagnosis showed the strongest
      association with the presence of later disease damage.The number of SLE
      diagnostic criteria at presentation was strongly associated with the total SDI
      score, and the renal damage was significantly more prevalent in patients with age
      at disease diagnosis below 10 years of age. A higher mean disease duration was
      found in patients with musculoskeletal damage. CONCLUSION: We found that
      cumulative organ damage, as measured by the SDI, was present in 43.9% of Egyptian
      patients with juvenile-onset SLE. The damage was significantly more likely in
      patients who had more SLE diagnostic criteria at time of disease presentation and
      NPS manifestations at the time of diagnosis.

PMID- 22152341
TI  - Eyes open to stem cells: safety trial may pave the way for cell therapy to treat
      retinal disease in patients.
AB  - A clinical trial using human embryonic stem cell (hESC) therapy for an inherited
      retinal degenerative disease is about to commence. The Advanced Cell Technology
      (ACT) trial will treat patients with Stargardt's macular dystrophy using
      transplanted retinal pigment epithelium derived from hESCs. Currently, no
      effective treatment is available for Stargardt's disease so a stem cell-based
      therapy that can slow progression of this blinding condition could represent a
      significant breakthrough. While there are some hurdles to clear, the ACT trial is
      a fine example of translational research that could eventually pave the way for a
      range of stem cell therapies for the retina and other tissues.

PMID- 22152343
TI  - A survey of nursing home organizational characteristics associated with
      potentially avoidable hospital transfers and care quality in one large British
      Columbia health region.
AB  - Hospitalization of nursing home residents can be futile as well as costly, and
      now evidence indicates that treating nursing home residents in place produces
      better outcomes for some conditions. We examined facility organizational
      characteristics that previous research showed are associated with potentially
      avoidable hospital transfers and with better care quality. Accordingly, we
      conducted a cross-sectional survey of nursing home directors of care in Vancouver
      Coastal Health, a large health region in British Columbia. The survey addressed
      staffing levels and organization, physician access, end-of-life care, and factors
      influencing facility-to-hospital transfers. Many of the modifiable organizational
      characteristics associated in the literature with potentially avoidable hospital
      transfers and better care quality are present in nursing homes in British
      Columbia. However, their presence is not universal, and some features, especially
      the organization of physician care and end-of-life planning and services, are
      particularly lacking.

PMID- 22152344
TI  - Which is important for preschoolers' production and repair of statements: what
      the listener knows or what the listener says?
AB  - Three- and four-year-olds participated in a referential communication task
      wherein they requested stickers from a knowledgeable or ignorant adult to
      complete a card. Following inadequate initial requests children were provided
      with three different feedback types: goal substitution (i.e. an incorrect sticker
      was provided), explicit statement of misunderstanding ('I don't know which one
      you mean'), and vague feedback ('Huh?'). Preschoolers' initial statements
      revealed sensitivity to the listener's perspective: more descriptors were
      provided when the listener did not have visual access to the card. Although
      listener's knowledge did not affect children's repair statements following
      feedback, the feedback type did: goal substitution elicited more repairs that
      included new descriptors, whereas vague responses elicited more repetition of
      initial requests than other feedback types. Children's age and verbal skills were
      related to the specific repair strategies used. Results demonstrate that
      preschoolers' use of cues from a conversational partner depends on the type of
      communicative task.

PMID- 22152342
TI  - Patient self-report for evaluating mild cognitive impairment and prodromal
      Alzheimer's disease.
AB  - Patient-reported outcome (PRO) measures are used to evaluate disease and
      treatments in many therapeutic areas, capturing relevant aspects of the disorder
      not obtainable through clinician or informant report, including those for which
      patients may have a greater level of awareness than those around them. Using PRO
      measures in mild cognitive impairment (MCI) and prodromal Alzheimer's disease
      (AD) presents challenges given the presence of cognitive impairment and loss of
      insight. This overview presents issues relevant to the value of patient report
      with emphasis on the role of insight. Complex activities of daily living
      functioning and executive functioning emerge as areas of particular promise for
      obtaining patient self-report. The full promise of patient self-report has yet to
      be realized in MCI and prodromal AD, however, in part because of lack of PRO
      measures developed specifically for mild disease, limited use of best practices
      in new measure development, and limited attention to psychometric evaluation.
      Resolving different diagnostic definitions and improving clinical understanding
      of MCI and prodromal AD will also be critical to the development and use of PRO
      measures.

PMID- 22152345
TI  - Magnetic moments, magnetic personalities: landmark papers from the pages of JMR -
      and the scientists behind them.

PMID- 22152346
TI  - Selective excitation in Fourier transform nuclear magnetic resonance. 1978.

PMID- 22152347
TI  - Radiofrequency pulse sequences which compensate their own imperfections. 1980.

PMID- 22152348
TI  - Selection of coherence-transfer pathways in NMR pulse experiments. 1984.

PMID- 22152349
TI  - Reflections of pathways: a short perspective on 'Selection of coherence transfer
      pathways in NMR pulse experiments'.

PMID- 22152350
TI  - Dynamic-angle spinning of quadrupolar nuclei. 1990.

PMID- 22152351
TI  - Dead-time free measurement of dipole-dipole interactions between electron spins.
      2000.

PMID- 22152352
TI  - The signal-to-noise ratio of the nuclear magnetic resonance experiment. 1976.

PMID- 22152353
TI  - A high-resolution NMR probe in which the coil and preamplifier are cooled with
      liquid helium. 1984.

PMID- 22152354
TI  - The first cryoprobe - some recollections.

PMID- 22152355
TI  - A common sense approach to peak picking in two-, three-, and four-dimensional
      spectra using automatic computer analysis of contour diagrams. 1991.

PMID- 22152356
TI  - A short recollection on the paper entitled "A common sense approach to peak
      picking in two-, three-, and four-dimensional spectra using automatic computer
      analysis of contour diagrams" by D.S. Garrett, R. Powers, A.M. Gronenborn, and
      G.M. Clore [J. Magn. Reson. 95 (1991) 214-220].
AB  - The Contour Approach to Peak Picking was developed to aid in the analysis and
      interpretation and of multidimensional NMR spectra of large biomolecules. In
      essence, it comprises an interactive graphics software tool to computationally
      select resonance positions in heteronuclear, 3- and 4D spectra.

PMID- 22152357
TI  - SIMPSON: a general simulation program for solid-state NMR spectroscopy. 2000.

PMID- 22152358
TI  - Dynamic nuclear polarization at 9T using a novel 250 GHz gyrotron microwave
      source. 2003.

PMID- 22152359
TI  - Dynamic nuclear polarization at 9T using a novel 250 gyrotron microwave source.
AB  - In the 1990's we initiated development of high frequency gyrotron microwave
      sources with the goal of performing dynamic nuclear polarization at magnetic
      fields (~5-23 T) used in contemporary NMR experiments. This article describes the
      motivation for these efforts and the developments that led to the operation of a
      gyrotron source for DNP operating at 250 GHz. We also mention results obtained
      with this instrument that would have been otherwise impossible absent the
      increased sensitivity. Finally, we describe recent efforts that have extended DNP
      to 460 GHz and 700 MHz (1)H frequencies.

PMID- 22152360
TI  - Rotational-echo double-resonance NMR. 1989.

PMID- 22152361
TI  - Three-dimensional triple-resonance NMR Spectroscopy of isotopically enriched
      proteins. 1990.

PMID- 22152362
TI  - Gradient-enhanced heteronuclear correlation spectroscopy: theory and experimental
      aspects. 1992.

PMID- 22152363
TI  - Gradient-enhanced spectroscopy. 1990.

PMID- 22152364
TI  - NMR studies of protein structure and dynamics. 2005.

PMID- 22152365
TI  - NMR Fourier zeugmatography. 1975.

PMID- 22152366
TI  - NMR Fourier zeugmatography.

PMID- 22152367
TI  - Biological and medical imaging by NMR. 1978.

PMID- 22152368
TI  - FLASH imaging: rapid NMR imaging using low flip-angle pulses. 1986.

PMID- 22152369
TI  - FLASH MR imaging: a success story since 25 years.

PMID- 22152370
TI  - A k-space analysis of small-tip-angle excitation. 1989.

PMID- 22152371
TI  - Microstructural and physiological features of tissues elucidated by quantitative
      diffusion-tensor MRI. 1996.

PMID- 22152372
TI  - Recollections about our 1996 JMR paper on diffusion anisotropy.
AB  - We provide scientific background information and personal accounts relating to
      our publication of "Microstructural and Physiological Features of Tissues
      Elucidated by Quantitative-Diffusion-Tensor MRI" in the Journal of Magnetic
      Resonance B. This paper provided a framework for measuring and mapping intrinsic
      features of diffusion anisotropy obtained from diffusion tensor MRI (DTI) data.

PMID- 22152373
TI  - [Strengthen researches on hyperlipaemia and fatty liver with Chinese
      characteristics].

PMID- 22152374
TI  - [The role of inflammation related ectopic lipid deposition in non-alcoholic fatty
      liver disease].

PMID- 22152375
TI  - [Pancreatic derived factor (PANDER) and non-alcoholic fatty liver disease
      (NAFLD)].

PMID- 22152376
TI  - [Cross-talk between endoplasmic reticulum and mitochondria in non-alcoholic fatty
      liver disease].

PMID- 22152377
TI  - [The pathophysiological role of gut in non-alcoholic fatty liver disease].

PMID- 22152378
TI  - [The role of Fas mutation on non-alcoholic steatohepatitis in mice].
AB  - OBJECTIVE: Our previous study indicated that the death receptor Fas played a key
      role on hepatocyte apoptosis in nutritional steatohepatitis in mice. This study
      aimed to explore whether Fas mutation accelerated hepatic steatosis and
      inflammatory infiltration in methionine-choline deficient (MCD) diet feeding
      mice. METHODS: Mice homozygous for the lymphoproliferation spontaneous mutation
      (C57BL/6J-Faslpr) and wild type C57BL/6J mice were fed with MCD diet for three
      weeks to induce non-alcoholic steatohepatitis (NASH). Serum alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG) and
      total cholesterol (TC) levels were detected by an Olympus AU5400 automatic
      chemical analyzer. The role of Fas gene mutation on NASH was assessed by
      comparing the severity of hepatic steatosis and inflammation in the liver
      sections, the mRNA and protein expressions of hepatic inflammatory and
      fibrogenesis related factors, proliferating cell nuclear antigen (PCNA) and
      transforming growth factor beta 1 (TGFb1). RESULTS: The serum ALT levels of the
      wild type and Faslpr mice fed with MCD were significant higher than that of the
      control mice (126.33+/-10.50 U/L vs (25.00+/-10.14) U/L, (160.33+/-48.29) U/L vs
      (18.33+/-9.08) U/L, with the LSD-t value 12.02, 5.08 respectively, the P
      value<0.001, 0.007 respectively. The serum ALT levels showed no significant
      difference between the Faslpr and wild type mice fed with MCD, with the LSD-t
      value 1.19, the P value 0.229. The serum AST, TG and TC levels showed neithere
      significant difference among the four groups. MCD diet induced hepatic steatosis
      and inflammatory infiltration in both of the wild type and Faslpr mice.
      Especially, severer hepatic injury was observed in Faslpr mice as compared with
      wild type mice. The mRNA expression levels of cell proliferation factor PCNA and
      fibrogenesis growth factor TGF b1 in wild type mice fed with MCD were
      significantly higher than that of the control mice (2.84+/-0.73, 2.77+/-0.54 vs
      1.31+/-0.18, 0.89+/-0.18), with the LSD-t value 4.99, 8.08 respectively, the P
      value 0.001, <0.001 respectively. The mRNA expression levels of PCNA and TGFb1 in
      Faslpr mice fed with MCD were significantly higher than that of the Faslpr
      control mice and the wild type mice fed with MCD (5.57+/-1.13, 5.73+/-0.89 vs
      1.04+/-0.16, 0.85+/-0.11 and 2.84+/-0.73, 2.77+/-0.54), with the LSD-t value
      10.15, 13.19 and 5.33, 6.91 respectively, the P value<0.001. The protein
      expressions levels of PCNA and TGFb1 were concordant with the mRNA. CONCLUSIONS:
      Faslpr promoted hepatic steatosis and inflammatory infiltration in mice fed with
      MCD diet, which might associated with excessive release of cell proliferative,
      inflammatory and fibrogenesis factors.

PMID- 22152379
TI  - [Establishment and identification of non-alcoholic fatty liver disease in chronic
      hepatitis B virus infected mice].
AB  - OBJECTIVE: To establish and identify an animal model of non-alcoholic fatty liver
      disease in chronic HBV infected mice. METHODS: Transgenic mice with sustaining
      HBV production were established by microinjection of ocyte. Then they were
      randomly assigned into 4 groups (male control, male NAFLD model, female control
      and female NAFLD model) and treated with high fat diet (2% cholesterol, 10% lard,
      88% forage) and common forage, respectively. NAFLD-related physical indexes,
      liver and kidney function, glucose and lipid metabolism were investigated at the
      time points of 8 weeks, 16 weeks and 24 weeks. Meanwhile, HBV type, serum levels
      of HBV DNA and HBeAg, immunohistochemical staining of hepatic HBsAg were
      detected. The establishment of NAFLD was evaluated by serum levels of total
      cholesterol (TC), triglycerides, glucose, aspartate aminotransferase (AST),
      alkaline phosphatase (ALP), alanine aminotransferase (ALT), gamma
      glutamyltransferase (GGT), etc. Histological changes were also analyzed by HE,
      oil red O and Masson's trichrome staining. The status of CHB was assessed on the
      basis of immunohistochemistry and real-time PCR. RESULTS: The body and liver
      weights, liver index in HBV transgenic mice were significantly increased in
      regardless of the gender of HFD feeding, and the levels of serum ALT, AST, ALP,
      GGT, TBIL, TBA, TC, TG, HDL-C, LDL and FBG were higher in HFD groups as compared
      with the control mice. Lipid droplets, cytologic ballooning and liver steatosis
      could be observed in most lobules of HFD groups after 8-week administration,
      fatty degeneration of hepatocytes, patch necrosis, mild to moderate chronic
      inflammatory infiltration were also observed in some of HFD feeding, reflecting
      the emerge of steatohepatitis. At the time point of 24-week perisinusoidal
      fibrosis and local fibrosis occurred in HFD groups. Immunohistochemical staining
      and real-time PCR analysis of the liver tissues showed positive signal of HBsAg
      in all groups of mice, although no significant difference was documented.
      CONCLUSION: Our study suggests that animal model of NAFLD can be established in
      HBV transgenic mice and provide a nice animal model for further studies on NAFLD
      with chronic hepatitis B infection.

PMID- 22152380
TI  - [SREBP-1c knockdown attenuated fatty degeneration in hepatic L02 cells and
      inhibited CCL2 and FGF21 protein expression].
AB  - OBJECTIVE: To study the effect of SREBP-1c silencing on lipid metabolism and
      expression of inflammatory chemokines in a NAFLD model with endoplasmic reticulum
      stress. METHOD: NAFLD model was established in L02 cells treated with oleic acid.
      SREBP-1c expression was inhibited using RNA interference with a p Silencer-1.0-U6
      4476 vector. After transfection with p Silencer-1.0-U6-4476 or control vector for
      0 h, 24 h, 48 h and 72 h, the extent of fatty degeneration was shown by Oil Red O
      staining. The mRNA and protein expression of inflammatory chemokine CCL2 and
      basic fibroblast growth factor-21 (FGF21) were determined by real time PCR and
      Western blot respectively. RESULTS: SREBP-1c silenced L02 cells showed fat
      droplets with smaller diameter and attenuated fatty deposition, as compared with
      control cells. The relative CCL2 mRNA levels in SREBP-1c silencing vector
      transfected L02 cells were 1.03+/-0.11 for 0 h, 1.11+/-0.21 for 24 h, 0.88+/-0.16
      for 48 h, and 1.05+/-0.15 for 72 h, which showed no significant difference as
      compared with control cells (P>0.05, respectively). In addition, no difference
      was found between the different time points within the same group (P>0.05).
      However, CCL2 protein levels in SREBP-1c silenced cells were 1.19+/-0.15, 1.07+/
      0.18, 0.48+/-0.14, and 0.05+/-0.24 after transfection for 0 h, 24 h, 48 h, and 72
      h respectively, which were significantly downregulated as compared to the control
      group (P<0.01). And CCL2 protein levels between different time points in SREBP-1c
      silenced cells were also distinct (P<0.01). The relative FGF21 mRNA levels in
      SREBP-1c silenced L-02 cells were 1.01+/-0.08, 0.91+/-0.22, 0.98+/-0.20, and
      1.02+/-0.12 for 0 h, 24 h, 48 h, and 72 h respectively, which were not
      statistically different as compared with the corresponding control cells.
      Statistic difference of FGF21 mRNA levels in SREBP-1c knockdown cells of
      different time points was not found (P>0.05). In striking contrast, robust down
      regulation of FGF21 protein in SREBP-1c silenced cells was observed, with 0.81+/
      0.05, 0.66+/-0.12, 0.58+/-0.08 and 0.19+/-0.13 after transfection for 0 h, 24 h,
      48 h and 72 h respectively, as compared to control group (P<0.01). And
      differences in FGF21 protein level between different time points in SREBP-1c
      silenced cells were also demonstrated (P<0.01). CONCLUSION: SREBP-1c knockdown
      attenuated fatty deposition in oleic acid treated L02 cells. In addition,
      silencing of SREBP-1c expression reduced expressions of CCL2 and FGF21 proteins
      posttranscriptionally, which may play a role in endoplasmic reticulum stress
      induced inflammatory response in NAFLD.

PMID- 22152381
TI  - [Clinical antiviral effects of Peg-IFNa-2a in patients with chronic hepatitis B].
AB  - OBJECTIVE: To evaluate antiviral effects of Peg-IFNa-2a in patients with chronic
      hepatitis B. METHODS: 92 chronic hepatitis B patients were enrolled to receive
      the treatment with Peg-IFNa-2a 180 MUg subcutaneous injection once weekly. The
      patients who did not get early response were divided into 3 groups: group 1,
      extend the treatment to 72 weeks; group 2, combined with nucleus(s)ide analogue
      (entecavir or adefovir) treatment; group 3, continue the treatment until 48
      weeks. HBV DNA and quantitative HBsAg were assessed at baseline, week 12, 24, 36
      and after 24 weeks follow-up. RESULTS: Patients in group 1 had significantly
      higher SVR rate (78.3%) than patients in group 3 (38.1%, X2=7.33, P<0.05). The
      mean reduction of HBsAg in group 1 at 24 weeks of post-treatment follow up was
      higher than that in group 3 (t=2.11, P<0.05). In group 2 the mean reductions of
      HBV DNA at 24 weeks of post-treatment follow up were (3.9+/-1.1) log10 copy/ml
      and (3.7+/-1.3) log10 copy/ml respectively with combination of entecavir or
      adefovir, both of which were significantly higher than that in group 3(t=8.45 and
      6.31, P<0.05); the SVR rates in the entecavir group and the adefovir group (83.3%
      and 85.7%, respectively) were significantly higher than that in group 3 (X2=8.20
      and 7.78, P<0.05); the mean reductions of HBsAg in the entecavir group and the
      adefovir group [(0.8+/-0.5) log10 IU/ml and (0.9+/-0.3) log10 IU/ml, respectively
      ] were significantly greater than group 3[(0.4+/-0.3) log10 IU/ml, t=3.05 and
      4.58, P<0.05]. The level of HBV DNA and C genotype were the main predictors of
      response. CONCLUSION: Individualizing therapy by prolonging the duration of Peg
      IFNa-2a treatment to 72 weeks or adding nucleoside analogues such as entecavir
      and adefovir in patients without early response may substantially increase the
      SVR rate and lead to the decrease of HBsAg.

PMID- 22152382
TI  - [The clinical significance of PreS1Ag and anti-PreS1 in patients with chronic
      hepatitis B].
AB  - OBJECTIVE: To investigate the positive ratio and clinical significance of PreS1Ag
      and anti-PreS1 in patients with chronic hepatitis B. METHODS: 428 patients with
      chronic HBV infection were collected, these patients were divided into e antigen
      positive CHB group, e antigen-negative CHB group, inactive HBsAg carrier group
      and HBsAg serum conversion group. The difference of positive ratio of PreS1Ag and
      anti-PreS1 among all groups or between every two groups were analyzed; The
      relationship of PreS1Ag and anti-PreS1 with HBV M and HBV DNA were also analyzed.
      SPSS13.0 software was used for statistical treatment. Fourfold table chi-square
      test or matched-pairs chi-square test was used for enumeration data, and
      independent sampler t test or rank-sum test was used for measurement data.
      RESULTS: The differences of PreS1Ag among four groups were statistically
      significant (X2=141.7, P<0.05). The positive ratio of PreS1Ag in e antigen
      positive CHB group was 95.7%, followed by 82.8% in e antigen-negative CHB group,
      13.2% in inactive HBsAg carrier group and 2.2% in HBsAg serum conversion group.
      The difference of positive ratio of anti-PreS1 between HBsAg seroconversion group
      and HBsAg positive group was statistically significant (X2=6.919, P<0.05), which
      indicated that anti-PreS1 had good correlation with HBsAg seroconversion. The
      average absorbance ratio of PreS1Ag in high viral replication group (179.30) was
      higher than that in low viral replication group (133.87), statistical
      significance appeared (Z=-3.86, P<0.05). Though the difference of absorbance
      ratio of anti-PreS1 between two groups had no statistical significance (P>0.05),
      descent trend was apparent with virus replication level ascending. We analyzed
      the concordance of anti-HBs and anti-PreS1 by matched-pairs chi-square test,
      result showed no statistical significance of detection rate between them,
      X2=0.262, P>0.05. Serum PreS1Ag, HBeAg or HBcAg in liver tissue in reflecting
      hepatitis B replication had correlation with HBV DNA (X2=33.840, 24.159, 4.854 in
      order, P<0.05). Correlation coefficient between PreS1Ag and HBV DNA was higher
      (r=0.628) than that between HBeAg and HBV DNA (r=0.563). CONCLUSION: PreS1Ag was
      more sensitive than HBeAg in diagnosing viral replication in patients with
      chronic hepatitis B. Anti-PreS1 as protective antibody may be involved in
      clearance of hepatitis B, positive result indicated recovery of chronic hepatitis
      B.

PMID- 22152383
TI  - [Study on the copy numbers and mRNA expression levels of the programmed death-1
      gene in chronic hepatitis B patients].
AB  - OBJECTIVE: To study the copy numbers and mRNA expression levels of the Programmed
      Death-1 gene in chronic hepatitis B patients and to analyze the differences of
      the copy numbers and mRNA expression levels of the gene in patients with
      different clinical outcomes. METHODS: Real time PCR was adopted to detect the PD
      1 gene copy numbers and their mRNA expressions in peripheral blood mononuclear
      cells (PBMCs) from 27 samples from healthy donors in Control group, 31 samples
      from chronic asymptomatic HBV carriers (ASC, n=31), 19 samples from chronic
      severe hepatitis B patients (CSH, n=19) and 29 samples from Primary hepatitis B
      Virus-related hepatocarcinoma (PHC, n=29). The differences and relationship of
      copy numbers and their mRNA expression levels among those groups were compared
      and analyzed by adopting Chi-square test and Rank sum test. RESULTS: PD-1 gene
      copy number deviated from 0 copy to 3 copies among all the 106 samples. In
      control group, ASC group, CSH group and PHC group, the percentages of cases of
      haploid (single) were 37.0%, 35.5%, 26.3% and 6.9%, respectively, the percentages
      of cases of diploid (double) were 55.5%, 58.0%, 63.2% and 82.8%, respectively,
      and the percentages of cases of triploid (triple) were 3.7%, 6.5%, 10.5% and
      10.3%, respectively. The percentage of cases of polyploid (diploid and triploid)
      in control group, ASC group, CSH group and PHC group were 59.3%, 64.5%, 73.7% and
      93.1%, respectively. The different distribution of PD-1 gene copy number of
      polyploid was significant in total samples (x2=9.583, P<0.05). Compared with
      Control Group and ASC group, the percentage of cases of polyploid in PHC group
      was lower with the x2 equals to 8.985 and 7.215 respectively and both with P less
      than 0.05. The difference between the two groups was statistically significant.
      The mean PD-1 gene copy numbers for these four groups were 1.59+/-0.63, 1.70+/
      0.52, 1.84+/-0.60 and 2.00+/-0.37 while the median were 0.002 54, 0.002 72, 0.002
      55 and 0.001 33 respectively. Except the control group, there was a uptrend in
      the other three groups while PD-1 gene mRNA expression presented a downtrend. The
      mean of PD-1 gene copy numbers of 2 and their mRNA expression levels were 19.59,
      32.57 and 33.22 for PHC, CSH and ASC groups among which PHC group had the lowest
      value, there was significant differences found in the comparison with F=5.395 and
      P<0.05. CONCLUSION: PD-1 gene copy numbers and their mRNA expression levels were
      different in chronic HBV infected patients with different transformation. It is
      valuable to follow up the patients with more than 1 copy number of PD-1 gene in
      long term.

PMID- 22152384
TI  - [Efficacy of interferon alpha with ribavirin for treatment of chronic Hepatitis
      C].
AB  - OBJECTIVE: To investigate the prevalence and distribution of HCV genotypes and
      the clinical effect of interferon-alpha combined with ribavirin treatment in
      chronic hepatitis C patients in Kunming. METHODS: 60 patients were divided into
      two groups based on drug therapies: PEG-interferon-a plus ribavirin treatment
      group for HCV 1b and interferon-a plus ribavirin treatment group for non-HCV-1b.
      Serum ALT levels and HCV RNA quantitations of the patients were detected during
      treatment and follow-up. RESULTS: The HCV genotypes of 60 patients were
      determined by type specific probe assay, and five different types were found.
      Their overall prevalence were 21.7% for type 1b, 5% for type 2a, 16.7% for type
      3a, 48.3% for type 3b, and 8.3% for type 6a. Sustained viral response rates for
      PEG-interferon treatment group were 46.1%, for interferon treatment group were
      74.4%. The abnormal rate of serum ALT after the treatment had no significant
      difference between HCV-1b and non-HCV-1b patients (P>0.05). All patients with
      early viral responses got sustained viral response. CONCLUSION: HCV-3b is the
      most dominant genotype in Kunming. The effect of PEG-interferon-a plus ribavirin
      treatment for genotype 1b is unsatisfactory. The early viral response is a good
      predictor for the responses to antiviral therapy in chronic hepatitis C patients.

PMID- 22152385
TI  - [The effect of 5-fluorouracil on enriching cancer stem cells of hepatoma cell
      line BEL-7402].
AB  - OBJECTIVE: To investigate the effect of 5-FU (5-fluorouracil) on enriching cancer
      stem cells of HCC cell line BEL-7402 and the biological characteristics of
      enriched cells. METHODS: The enriching concentration of 5-FU was determined by
      CCK-8 (cell counting kit-8). Flow Cytometry was used to determine the changes in
      cell cycle and positive expression ratio of surface marker CD56, CD54, EpCAM and
      CD133. The self-renewal and differentiation of positive cells were tested by
      colony formation assay, and were compared with the control group. RESULTS:
      Enriching concentration of 5-FU was determined as 10 MUg/ml with 48 h incubation.
      After enrichment, G0/G1 phase cells increased from 57.50 %+/-0.98% to 68.70%+/
      3.41% (P<0.05). Whereas S phase cells decreased from 40.26%+/-4.12% to 31.80%+/
      4.15% (P<0.01); G2/M phase cells disappeared in experimental group, and was
      5.80%+/-1.87% in control group (P<0.01). The proportion of the cell cycle changed
      with significant statistical differences. Meanwhile, positive rate of cell
      surface makers CD56, CD54, EpCAM and CD133 increased from 0.57%+/-0.12%, 8.10%+/
      6.79%, 0.3%+/-0.01% and 3.20%+/-0.99% to 4.13%+/-0.06%, 50.08%+/-1.69%, 0.55%+/
      0.07% and 10.51%+/-1.13%, respectively. The difference was significant (P<0.05).
      The colony forming ratio of CD56, CD54, EpCAM and CD133 negative cells and
      positive cells were 2.11%+/-0.21%, 3.32%+/-0.31%; 0.86%+/-0.101%, 2.40%+/-0.52 %;
      7.19%+/-0.56%, 7.73%+/-0.71%; 2.70%+/-0.26%, 5.75%+/-0.81%, respectively, and
      significant differences were found between (P<0.05). CONCLUSION: 5-fluorouracil
      enriched the cancer stem cell population in HCC cell line BEL-7402. CD56 and CD54
      can be used as important surface markers in research of liver cancer stem cells.

PMID- 22152386
TI  - [Hepatic lineage differentiation of hepatic progenitor cells by bone
      morphogenetic protein or leukemia inhibitory factor].
AB  - OBJECTIVE: To search for the optimal approach for hepatocyte-directed
      differentiation of hepatic progenitor cells and investigate the molecular
      mechanism of the hepatic differentiation. METHODS: Hepatic progenitor cells were
      infected with recombinant adenovirus which containing human LIF, BMP2 or BMP9
      gene. The maturation and differentiation of progenitor cells were examined by PAS
      staining and ICG uptake methods at 4, 7 and 10 days post infection. The
      production of Albumin (Alb) was measured by luciferase activity at day 4, 7, 10
      and 14. RESULTS: PAS staining assay revealed that BMP2 and BMP9 enhanced glycogen
      storage in hepatic progenitor cells most obviously at day 7. The percentages of
      positive cells were 30% and 45% respectively at 7 days post-infection. Meanwhile,
      40% and 30% cells were positive by ICG uptake assay after BMP2 and BMP9
      induction. Luciferase activity indicated that BMP9 induced ALB-Luc activity most
      significantly at day 7. However, less inductive activity was found in LIF-treated
      group. CONCLUSION: These results indicated tuat hepatic progenitor cells were
      differentiated into hepatocyte-like cells by BMPs and LIF induction.

PMID- 22152387
TI  - [The effect of far upstream element binding protein-1 on the pathogenesis of
      human hepatocellular carcinomas].

PMID- 22152388
TI  - [Mutations and expressions of p53 gene during the liver tumor promotion by
      microcystin LR].

PMID- 22152389
TI  - [Clinical outcomes of long-term anti-inflammatory and hepatoprotective treatments
      in patients with chronic hepatitis B].

PMID- 22152390
TI  - [Effect of RNA interference targeting PTTG1 gene on cell proliferation and
      apoptosis in hepatic cancer cells].

PMID- 22152391
TI  - [Bone marrow mesenchymal stem cells contribute to liver fibrosis].

PMID- 22152392
TI  - [Nodular regenerative hyperplasia of liver: a case report].

PMID- 22152393
TI  - [A brief report on the fourth national congress of fatty liver disease].

PMID- 22152394
TI  - [Difference between non-alcoholic fatty liver disease and alcoholic liver
      disease].

PMID- 22152395
TI  - [Progression on the use of vasoactive agents in the treatment of hepatorenal
      syndrome].

PMID- 22152396
TI  - The use of albendazole and diammonium glycyrrhizinate in the treatment of
      eosinophilic meningitis in mice infected with Angiostrongylus cantonensis.
AB  - Angiostrongylus cantonensis (A. cantonensis) infection causes eosinophilic
      meningitis in humans. Eosinophilia and a Th2-type immune response are the crucial
      immune mechanisms for eosinophilic meningitis. CD4+CD25+ regulatory T cells
      (Treg) are involved in the pathogenesis of A. cantonensis. Diammonium
      glycyrrhizinate (DG) is a compound related to glycyrrhizin (GL), a triterpene
      glycoside extracted from liquorice root. We investigated the curative effects and
      probable mechanisms of therapy involving a combination of albendazole and DG in
      BALB/c mice infected with A. cantonensis, and compared these with therapy
      involving albendazole and dexamethasone. We analysed survival time, body weight,
      signs, eosinophil numbers, immunoglobulin E (IgE), interleukin-5 (IL-5), and
      eotaxin concentrations, numbers and Foxp3 expression of CD4+CD25+ Treg, worm
      recovery and histopathology. The present results demonstrated that the
      combination of albendazole and DG could increase survival time more efficiently
      and relieve neurological dysfunction; decrease weight loss, eosinophil numbers,
      concentrations of IgE, IL-5 and eotaxin, the number and expression of Foxp3 of
      CD4+CD25+ Treg; and improve worm recovery and histopathology changes in treated
      animals, compared with the combination of albendazole and dexamethasone. The
      observations presented here suggest that the albendazole and dexamethasone
      combination could be replaced by the combination of albendazole and DG.

PMID- 22152397
TI  - Adjuvant or radical fractionated stereotactic radiotherapy for patients with
      pituitary functional and nonfunctional macroadenoma.
AB  - PURPOSE: To evaluate the efficacy and toxicity of stereotactic fractionated
      radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA). METHODS AND
      MATERIALS: Between March 2000 and March 2009, 27 patients (male to female ratio,
      1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients
      was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was
      administered for salvage treatment after surgical resection (transphenoidal
      resection in 23, transphenoidal resection followed by craniotomy in 2 and
      multiple transphenoidal resections in another patient). In 10 (37%) patients, the
      PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone
      secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients
      had PMA abutting and compressing the optic chiasm, respectively. Mean tumor
      volume was 2.9 +/- 4.6 cm3. Eighteen (66.7%) patients had hypopituitarism prior
      to SFRT. The mean follow-up period after SFRT was 72.4 +/- 37.2 months. RESULTS:
      Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%)
      other patients. Two (7.4%) patients had tumor growth inside the prescribed
      treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT.
      Biochemical remission occurred in 3 (30%) patients with functional PMA. Two
      patients with normal anterior pituitary function before SFRT developed new
      deficits 25 and 65 months after treatment. The 5-year survival without new
      anterior pituitary deficit was thus 95.8%. Five patients with visual field defect
      had improved visual function and 1 patient with no visual defect prior to SFRT,
      but an optic chiasm abutting tumor, had a decline in visual function. The
      estimated 5-year vision and pituitary function preservation rates were 93.2% and
      95.8%, respectively. CONCLUSIONS: SFRT is a safe and effective treatment for
      patients with PMA, although longer follow-up is needed to evaluate long-term
      outcomes. In this study, approximately 1 patient with visual field defect out of
      two had an improved visual function.

PMID- 22152398
TI  - The relationships of environment and personal characteristics to agitated
      behaviors in nursing home residents with dementia.
AB  - OBJECTIVE: To explore the impact of personal attributes, environmental
      attributes, and the presentation of 9 categories of stimuli on agitation in
      nursing home residents with dementia. METHOD: Participants in this randomized,
      controlled, observational cross-sectional study were 193 residents of 7 nursing
      homes, all with a diagnosis of dementia, for whom we obtained data pertaining to
      cognitive functioning (via the Mini-Mental State Examination), performance of
      activities of daily living (Minimum Data Set), and role-identity/activities of
      past interest (Self-Identity Questionnaire). Environmental attributes (eg, noise,
      lighting) and direct observations of agitation (primary outcome) were recorded
      via the Agitation Behavior Mapping Inventory. Engagement was measured using the
      Observational Measurement of Engagement. Both agitation and engagement were
      assessed for each stimulus (including a control condition). RESULTS: Univariate
      findings (ie, for 1 explanatory variable at a time) showed agitation to be
      related to several personal attributes--ie, female gender was related to verbal
      agitation (P < .0001); low cognitive function was related to total, verbal, and
      physical agitation (P < .001 for each); low performance of activities of daily
      living was significantly related to all types of agitation (P < .01 for total
      agitation and P < .05 for each type of agitation); and unclear speech was
      significantly related to total agitation (P < .01). Eight of the 9 stimulus
      categories were significantly related to decreased levels of agitation, with ORs
      ranging from 0.37 (live human stimuli, P < .001) to 0.79 (inanimate social
      stimuli, P < .05). Higher levels of engagement were related to lower levels of
      agitation (P < .001 for total agitation). In the multivariate analyses, higher
      cognitive function (P < .001), male gender (P < .05), level of engagement with
      stimuli (eg, duration of engagement for 3 minutes or longer, P < .05), and all 9
      stimulus categories, with the exception of music, were independently predictive
      of lower levels of agitation (P < .001). CONCLUSIONS: The finding that both type
      of stimuli and engagement level with the stimuli were significant predictors of
      agitation underscores the importance of engagement as a determinant of agitation
      levels.

PMID- 22152399
TI  - Declining benzodiazepine use in veterans with posttraumatic stress disorder.
AB  - OBJECTIVE: Clinical practice guidelines issued by the US Department of Veterans
      Affairs (VA) and the Department of Defense caution against benzodiazepine use
      among veterans with posttraumatic stress disorder (PTSD) because of insufficient
      evidence for efficacy and emerging safety concerns. We examined recent trends in
      benzodiazepine prescribing among veterans with PTSD in terms of frequency of use,
      duration of use, and dose. METHOD: Administrative VA data from fiscal years 1999
      through 2009 were used to identify veterans with PTSD according to ICD-9 codes
      extracted from inpatient discharges and outpatient encounters. Benzodiazepine use
      among these individuals was determined for each fiscal year by using prescription
      drug files. Modal daily doses were examined by using standard daily dosage units.
      RESULTS: The number of veterans receiving care for PTSD in the VA increased from
      170,685 in 1999 to 498,081 in 2009. The proportion of individuals receiving a
      benzodiazepine decreased during this time period from 36.7% to 30.6%. In
      addition, the proportion of long-term users (> 90 days) decreased from 69.2% to
      64.1%, and daily dose decreased from 2.1 to 1.8 standard daily dosage units.
      CONCLUSIONS: Decreasing benzodiazepine use among veterans with PTSD is
      encouraging. However, the frequency of use remains above 30%, and focused
      interventions may be required to achieve further reductions. Given the growing
      number of veterans being diagnosed and treated for PTSD, minimizing
      benzodiazepine exposure will remain a vital policy issue for the VA.

PMID- 22152400
TI  - Maternal depression and anxiety differentially impact fetal exposures during
      pregnancy.
AB  - OBJECTIVE: To examine the association between severity of maternal depression and
      anxiety during pregnancy and the maternal use of medicinal agents and habit
      forming substances. METHOD: Participants in a prospective study of prenatal DSM
      IV depressive and anxiety disorders at the Emory Women's Mental Health Program
      who completed weekly documentation of prenatal drug exposure and >= 3
      administrations of the Hamilton Depression Rating Scale (HDRS) or Hamilton
      Anxiety Rating Scale (HARS) were included. The primary outcome measures were the
      HDRS and HARS. Correlation coefficients were computed for cumulative drug
      exposure with HDRS area under the curve (AUC) and HARS AUC. Data collection was
      completed between January 2007 and June 2010. RESULTS: Among 195 participants,
      both HDRS AUC and HARS AUC were negatively correlated with prenatal vitamin
      exposure (r = -0.22 [P = .002] and r = -0.26 [P = .0003], respectively) and
      positively correlated with tobacco (r = 0.21 [P = .003] and r = 0.20 [P = .006],
      respectively) and hypnotic (r = 0.28 [P < .0001] and r = 0.19 [P = .008],
      respectively) exposure. Only HDRS AUC correlated with exposure to antiemetics (r
      = 0.14 [P = .05]), opioid analgesics (r = 0.14 [P = .05]), and all prescription
      drugs (r = 0.16 [P = .02]). Only HARS AUC correlated with benzodiazepine exposure
      (r = 0.17 [P = .02]). CONCLUSIONS: Both prenatal depression and anxiety are
      associated with decreased prenatal vitamin compliance and increased use of
      hypnotics and tobacco, but only depression is associated with exposure to a
      broader array of medications targeting physical symptoms that often accompany
      depression. These findings confirm and extend previous studies, underscoring the
      importance of addressing prenatal depression and anxiety.

PMID- 22152401
TI  - Short-term dynamic psychotherapy versus pharmacotherapy for major depressive
      disorder: a randomized, placebo-controlled trial.
AB  - OBJECTIVE: To determine whether supportive-expressive psychotherapy (SET), a form
      of dynamic psychotherapy, and pharmacotherapy + clinical management (MED) for
      major depressive disorder (MDD) are more effective than pill-placebo + clinical
      management (PBO). METHOD: This National Institute of Mental Health (NIMH)
      sponsored randomized controlled trial was conducted (from November 2001 through
      June 2007) at the University of Pennsylvania Medical School. The sample included
      156 patients diagnosed with MDD (DSM-IV) and having a 17-item Hamilton Rating
      Scale for Depression (HRSD(17)) score >= 14 for at least 2 consecutive weeks.
      This was an underserved sample in which 41% were male, 52% were self-designated
      minorities, and 76% had an annual income under $30,000. Treatment lasted 16
      weeks. Medication patients not responsive by week 8 (maximum dose 200 mg/d of
      sertraline) were switched to venlafaxine (maximum dose 375 mg/d). Nonresponsive
      placebo patients at week 8 were switched to a different placebo. RESULTS:
      Patients' depression improved over the 16 weeks (P < .0001), with no between
      group differences (P = .95), even among severely (HRSD(17) score >= 20) depressed
      patients (P = .45). Response rates did not differ between groups (P = .73).
      Gender and minority status moderated outcome (P = .014), with psychotherapy more
      efficacious for minority men than MED (P = .027, Cohen d = 1.02) and PBO (P =
      .019, d = 1.09). PBO was more efficacious for white men than MED (P = .03, d =
      0.62) and SET (P = .003, d = 1.07). For white women, MED (P = .005, d = 0.77) and
      SET (P = .033, d = 0.71) were more efficacious than placebo. No differences among
      treatments were found for minority women. CONCLUSIONS: This trial of urban MDD
      patients failed to confirm that either active treatment was better than placebo.
      Minority status and gender had significant and differential effects on outcome
      that warrant replication in future studies. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00043550.

PMID- 22152402
TI  - Double-blind, randomized, placebo-controlled long-term maintenance study of
      aripiprazole in children with bipolar disorder.
AB  - BACKGROUND: This study evaluates the long-term efficacy of aripiprazole compared
      to placebo in children with bipolar disorders. METHOD: Outpatients aged 4 to 9
      years meeting DSM-IV criteria for a bipolar disorder (I, II, not otherwise
      specified, cyclothymia) were eligible to receive up to 16 weeks of open-label
      treatment with aripiprazole (phase 1). Patients were randomized into the 72-week
      double-blind phase of the study once they met a priori response criteria for
      stabilization (phase 2). During phase 2, patients either remained on their
      current aripiprazole regimen or began a double-blind taper with aripiprazole
      discontinued and switched to placebo. The primary outcome measure for phase 2 was
      time to discontinuation due to a mood event. RESULTS: Patients were recruited
      between May 2004 and November 2008. Following phase 1, in which 96 patients
      received aripiprazole, 30 patients (mean age = 7.1 years) were randomly assigned
      to continue aripiprazole and 30 patients (mean age = 6.7 years) were randomly
      assigned to placebo. The mean (SD) dose of aripiprazole prior to randomization
      for these patients was 6.4 (2.1) mg/d. Patients randomly assigned to aripiprazole
      were enrolled significantly longer until time to study discontinuation due to a
      mood event (6.14 median weeks, SE +/- 11.88 weeks; P = .005) and discontinuation
      for any reason (including mood events) (4.00 median weeks, SE +/- 3.91 weeks; P =
      .003) than those randomly assigned to placebo (mood event, 2.29 median weeks, SE
      +/- 0.38 weeks; any reason, 2.00 median weeks, SE +/- 0.31 weeks). Regardless of
      random assignment, both the aripiprazole and placebo groups showed substantial
      rates of withdrawal from maintenance treatment over the initial 4 weeks (15/30
      [50%] for aripiprazole; 27/30 [90%] for placebo), suggesting a possible nocebo
      effect (ie, knowledge of possibly switching from active medication to placebo
      increasing concern about relapse). The most frequently reported adverse events
      during double-blind aripiprazole therapy included stomach pain (n = 10, 33%),
      increased appetite (n = 9, 30%), and headaches (n = 9, 30%). CONCLUSIONS: Despite
      the possibility of a nocebo effect, these results suggest that aripiprazole may
      be superior to placebo in the long-term treatment of pediatric patients following
      stabilization with open-label aripiprazole. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00194077.

PMID- 22152403
TI  - Insomnia and objectively measured sleep disturbances predict treatment outcome in
      depressed patients treated with psychotherapy or psychotherapy-pharmacotherapy
      combinations.
AB  - OBJECTIVE: Insomnia and objectively measured sleep disturbances predict poor
      treatment outcomes in patients with major depressive disorder (MDD). However,
      prior research has utilized individual clinical trials with relatively small
      sample sizes and has focused on insomnia symptoms or objective measures, but not
      both. The present study is a secondary analysis that examines the degree to which
      insomnia, objective sleep disturbances, or their combination predicts depression
      remission following pharmacotherapy and/or psychotherapy treatment. METHOD:
      Participants were 711 depressed (DSM criteria) patients drawn from 6 clinical
      trials. Remission status, defined as a score of <= 7 on the Hamilton Depression
      Rating Scale (HDRS) over 2 consecutive months, served as the primary outcome.
      Insomnia was assessed via the 3 sleep items on the HDRS. Objectively measured
      short sleep duration (total sleep time <= 6 hours) and prolonged sleep latency (>
      30 minutes) or wakefulness after sleep onset (> 30 minutes) were derived from in
      laboratory polysomnographic sleep studies. Logistic regression predicted the odds
      of nonremission according to insomnia, each of the objective sleep disturbances,
      or their combination, after adjusting for age, sex, treatment modality, and
      baseline depressive symptoms. RESULTS: Prolonged sleep latency alone (OR = 3.53;
      95% CI, 1.28-9.73) or in combination with insomnia (OR = 2.11; 95% CI, 1.13-3.95)
      predicted increased risk of nonremission. In addition, insomnia and sleep
      duration individually and in combination were each associated with a
      significantly increased risk of nonremission (P values < .05). CONCLUSIONS:
      Findings suggest that objectively measured prolonged sleep latency and short
      sleep duration independently or in conjunction with insomnia are risk factors for
      poor depression treatment outcome.

PMID- 22152404
TI  - Executive function predicts response to antiaggression treatment in
      schizophrenia: a randomized controlled trial.
AB  - OBJECTIVE: Despite extensive experience with antipsychotic medications, we have
      limited capacity to predict which patients will benefit from which medications
      and for what symptoms. Such prediction is of particular importance for the proper
      treatment of violence. Our goal was to determine whether executive function
      predicts outcome of treatment for aggressive behavior and whether such prediction
      varies across medication groups. METHOD: Ninety-nine physically aggressive
      inpatients (aged 18-60 years) with schizophrenia or schizoaffective disorder
      (diagnosed according to DSM-IV) who completed tests of executive function were
      randomly assigned in a double-blind, parallel-group, 12-week trial to clozapine
      (n = 32), olanzapine (n = 32), or haloperidol (n = 35). The number and severity
      of aggressive events as measured by the Modified Overt Aggression Scale (MOAS)
      were the outcome measures. Psychopathology and medication side effects were also
      assessed. The study was conducted from 1999 to 2004. RESULTS: Poor executive
      function predicted higher levels of aggression, as measured by MOAS scores over
      the 12-week period, in all 3 medication groups (F(1,98) = 222.2, P < .0001).
      There was, however, a significant interaction effect between medication grouping
      and executive function (F(1,98) = 15.32, P < .001): clozapine exerted an
      antiaggression effect even in the presence of executive dysfunction. CONCLUSIONS:
      Executive function was a strong predictor of response to antiaggression treatment
      in all medication groups, but clozapine still retained clinical efficacy in the
      presence of poor executive functioning. Olanzapine was particularly efficacious
      in the absence of executive dysfunction. These findings have important
      implications for a targeted approach to the treatment of aggression in patients
      with schizophrenia. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01123408.

PMID- 22152406
TI  - A systems-based mathematical modelling framework for investigating the effect of
      drugs on solid tumours.
AB  - BACKGROUND: Elucidating the effects of drugs on solid tumours is a highly
      challenging multi-level problem, since this involves many complexities associated
      with transport and cellular response, which in turn is characterized by highly
      non-linear chemical signal transduction. Appropriate systems frameworks are
      needed to seriously address the sources of these complexities, especially from
      the cellular side. RESULTS: We develop a skeletal modelling framework
      incorporating interstitial drug transport, intracellular signal processing and
      cell population descriptions. The descriptions aim to appropriately capture the
      nature of information flow. The model is deliberately formulated to start with
      simple intracellular descriptions so that additional features can be incorporated
      in a modular fashion. Two kinds of intracellular signalling modules which
      describe the drug effect were considered, one a monostable switch and the other a
      bistable switch. Analysis of our model revealed how different drug stimuli can
      lead to cell killing in the tumour. Interestingly both modules considered
      exhibited similar trends. The effects of important parameters were also studied.
      CONCLUSIONS: We have created a predictive systems platform integrating drug
      transport and cellular response which can be systematically augmented to include
      additional layers of cellular complexity. Our results indicate that intracellular
      signalling models which are qualitatively different can give rise to similar
      behaviour to simple (and typical) stimuli, and that validating intracellular
      descriptions must be performed with care by considering a variety of drug
      stimuli.

PMID- 22152405
TI  - Placebo-controlled adjunctive trial of pramipexole in patients with bipolar
      disorder: targeting cognitive dysfunction.
AB  - OBJECTIVE: Patients with bipolar disorder suffer from significant cognitive
      impairment that contributes directly to functional disability, yet few studies
      have targeted these symptoms for treatment, and the optimal study design remains
      unclear. We evaluated the effects of the dopamine D2/D3 receptor agonist
      pramipexole on cognition in bipolar disorder. METHOD: Fifty stable outpatients
      with DSM-IV-diagnosed bipolar I or bipolar II disorder enrolled in an 8-week,
      double-blind, randomized, placebo-controlled cognitive enhancement trial between
      July 2006 and April 2010. Patients completed neurocognitive testing at baseline
      and at week 8, and the primary outcome measures were change scores calculated for
      each of the 11 tasks. Symptoms and side effects were monitored weekly. RESULTS:
      Forty-five patients completed the study (placebo, n = 24; pramipexole, n = 21),
      and groups were well matched on demographic and clinical features. Primary
      cognitive analyses indicated no compelling cognitive benefit of pramipexole
      versus placebo; however, secondary analyses highlight several important
      methodological issues for future trials and identify a subgroup of patients who
      might benefit more readily from cognitive enhancement strategies. This outcome
      suggests that the study design played a very important role in the results
      implying a failed rather than altogether negative trial. Specifically, we found
      that even very subtle, subsyndromal mood symptoms at baseline had a significant
      influence on the degree of improvement due to active drug, with strictly euthymic
      patients faring best (multivariate analysis of variance, P = .03 in euthymic
      subgroup). In addition, the extent of baseline cognitive impairment also
      contributed to the likelihood of treatment response. Finally, concomitant
      medications may weaken, or in some cases enhance, response to cognitive treatment
      and should be accounted for in study design. CONCLUSIONS: Although our results
      point toward a lack of clear effect of pramipexole on cognition in bipolar
      patients, our data revealed a potentially beneficial effect of pramipexole in a
      subgroup, providing some enthusiasm for pursuing this line of research in the
      future. Moreover, this study emphasizes the importance of rigorous subject
      selection for cognitive trials in bipolar illness. Future studies will be
      necessary to determine the possible clinical and functional implications of these
      results. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00597896.

PMID- 22152407
TI  - Elsevier/Oxford Centre for Diabetes, Endocrinology and Metabolism Junior Research
      Prize in Endocrinology: ENDO 2011 conference report.

PMID- 22152409
TI  - [A healthy young man with lost ribs].
AB  - A 19-year-old man received a routine medical exam, he had no medical history. A
      defect on the left thoracic wall was noted and an X-ray and CT-scan of the thorax
      showed osteolysis of the 3rd and 4th rib. Histopathology of surgical biopsies
      revealed non-malignant vascular proliferation consistent with Gorham's disease.

PMID- 22152410
TI  - [Renal infarction in two patients with acute abdominal pain].
AB  - BACKGROUND: Renal infarction is a condition not known to every physician, with
      often non-specific symptoms. The diagnosis is therefore often not considered
      initially in patients with acute abdominal pain. CASE DESCRIPTIONS: In a 77-year
      old man a renal infarction was found by chance on a CT-scan performed performed
      for the evaluation of dyspnoea. Previously he had visited the emergency unit with
      abdominal pain, in retrospect attributable to renal infarction. A 61-year-old man
      initially labelled as suffering from gastro-enteritis was diagnosed correctly
      with renal infarction after his renal function deteriorated and the lactate
      dehydrogenase (LDH) activity increased. CONCLUSION: A raised serum creatinine
      level and LDH activity are classic indicators of renal infarction. In addition,
      most patients have haematuria. Typical wedge-shaped perfusion defects are visible
      on a CT-scan with intravenous contrast. Timely diagnosis of renal infarction is
      important both for the prevention of recurrence of thromboembolic complications
      and for potential revascularisation. The diagnosis of renal infarction should be
      included in the differential diagnosis in patients with acute abdominal pain.

PMID- 22152408
TI  - Histological damage and inflammatory response elicited by Monobothrium wageneri
      (Cestoda) in the intestine of Tinca tinca (Cyprinidae).
AB  - BACKGROUND: Among the European cyprinids, tench, Tinca tinca (L.), and the
      pathological effects their cestodes may effect, have received very little or no
      attention. Most literature relating to Monobothrium wageneri Nybelin, 1922, a
      common intestinal cestode of tench, for example, has focused on aspects of its
      morphology rather than on aspects of the host-parasite interaction. RESULTS:
      Immunopathological and ultrastructural studies were conducted on the intestines
      of 28 tench, collected from Lake Piediluco, of which 16 specimens harboured tight
      clusters of numerous M. wageneri attached to the intestinal wall. The infection
      was associated with the degeneration of the mucosal layer and the formation of
      raised inflammatory swelling surrounding the worms. At the site of infection, the
      number of granulocytes in the intestine of T. tinca was significantly higher than
      the number determined 1 cm away from the site of infection or the number found in
      uninfected fish. Using transmission electron microscopy, mast cells and
      neutrophils were frequently observed in close proximity to, and inside, the
      intestinal capillaries; often these cells were in contact with the cestode
      tegument. At the host-parasite interface, no secretion from the parasite's
      tegument was observed. Intense degranulation of the mast cells was seen within
      the submucosa and lamina muscularis, most noticeably at sites close to the
      tegument of the scolex. In some instances, rodlet cells were encountered in the
      submucosa. In histological sections, hyperplasia of the mucous cells, notably
      those giving an alcian blue positive reaction, were evident in the intestinal
      tissues close to the swelling surrounding the worms. Enhanced mucus secretion was
      recorded in the intestines of infected tench. CONCLUSIONS: The pathological
      changes and the inflammatory cellular response induced by the caryophyllidean
      monozoic tapeworm M. wageneri within the intestinal tract of an Italian
      population of wild tench is reported for the first time.

PMID- 22152411
TI  - [Suicide attempt with antidepressants ordered from the Internet].
AB  - BACKGROUND: Since its launch, the Internet has developed into a mass medium with
      1.6 billion people using it worldwide. Due to anonymity, its wide reach and the
      infinite stream of information from the Internet, almost anything can be found on
      it. This includes medicines that can normally only be acquired by way of a
      doctor's prescription. CASE DESCRIPTION: A 27-year-old man made a suicide attempt
      using psychoactive drugs he got from an illegal website in India. This caused him
      to develop status epilepticus, rhabdomyolysis, renal insufficiency and pulmonary
      oedema for which he had to be admitted to intensive care. The patient was treated
      with medicine, cardioversion, ventilation and haemofiltration and recovered. He
      was referred to a psychiatric centre. CONCLUSION: The number of illegal online
      pharmaceutical websites on the Internet has increased drastically in the last
      decade. These websites sell medicines without prescription to consumers and the
      traditional doctor/patient consultation does not therefore take place. Many
      medicines that are delivered contain the wrong concentration or the wrong active
      ingredient and are often contaminated with other substances. The ease with which
      this life-threatening medicine can be ordered online without a doctor's
      supervision is a possible risk to public health.

PMID- 22152412
TI  - [The kidney: target for blood glucose-lowering therapy].
AB  - Diabetes mellitus is characterised by a dysregulated glucose metabolism and is
      accompanied by an elevated risk of micro- and macrovascular complications.
      Despite the current array of drugs, a substantial number of patients do not meet
      the recommended target values for blood glucose, blood pressure and other
      cardiovascular risk factors. This calls for more effective treatment strategies.
      The sodium-dependent glucose cotransporter 2 (SGLT2) located in the proximal
      tubule of the kidney reabsorbs virtually all filtered glucose and plays an
      important role in glucose regulation. Inhibition of SGLT2 results in increased
      urinary glucose excretion, and reduction of plasma glucose and HbA1c levels. In
      addition, SGLT2 inhibition reduces blood pressure and body weight, and there seem
      to be positive changes in the triglyceride concentration. Because of these
      beneficial effects, oral SGLT2 inhibitors could be important in the treatment of
      diabetes mellitus type 2.- Long-term studies are needed to confirm if they lower
      the cardiovascular risk and if they can be used safely. The possible connection
      between increased urinary glucose excretion and urogenital infections also
      requires further investigation.

PMID- 22152413
TI  - [Hypoglycaemia unawareness: report it to the CBR (the Dutch Driving Test
      Organisation) and revoke the licence to drive].
AB  - The Dutch legislator has adopted the point of view that people with diabetes and
      hypoglycaemia unawareness are unfit for driving a motor vehicle because
      hypoglycaemia unawareness carries with it an unacceptable risk for traffic
      accidents. There is no legal obligation for people in possession of a driving
      license to report changes to their state of health such as the appearance of
      hypoglycaemia unawareness. We argue that patients with newly diagnosed diabetes
      should inform the Driving Test Organisation about changes to their health status
      for moral reasons, and for reasons of judicial liability. This subject should be
      included in patient education, as should be strategies to minimise the risk of
      hypoglycaemia. In exceptional cases, the physician may opt to breech medical
      confidentiality and report the presence of hypoglycaemia unawareness in order to
      avert immediate, severe danger.

PMID- 22152414
TI  - [Mesalazine and sulphasalazine for Crohn's disease: few indications, severe
      adverse reactions].
AB  - We report 3 cases of the occurrence of adverse events in patients with Crohn's
      disease who were given aminosalicylic acids. The first case involved a 43-year
      old woman who developed interstitial pneumonitis requiring intubation after
      switching from mesalazine to sulphasalazine. Thereafter, mesalazine was used
      without complications. When sulphasalazine was reintroduced, the symptoms
      recurred. A second patient was a 56-year-old man who experienced worsening of
      abdominal symptoms after commencing mesalazine for an exacerbation of Crohn's
      disease; these symptoms improved following discontinuation of mesalazine. A third
      patient, a 23-year-old woman, had been treated with mesalazine for Crohn's
      disease for 6 months when budesonide was added because of insufficient response.
      After 3 weeks she was hospitalized for acute pancreatitis, which resolved after
      both medications were discontinued. Pancreatitis due to budesonide has not been
      previously described, but mesalazine is known to cause pancreatitis even after
      uncomplicated long-term use. Although effective in ulcerative colitis,
      aminosalicylic acid is not an effective treatment for Crohn's disease in general.
      Although adverse effects are rare, physicians should be aware of them and avoid
      unnecessary use.

PMID- 22152415
TI  - [Patients on the collaboration between occupational and curative physicians].
AB  - OBJECTIVE: Investigating patient experiences on the collaboration between
      occupational physicians and treating physicians, and clarifying why this type of
      cooperation is more difficult to get off the ground than would normally be
      expected. DESIGN: Qualitative focus group research. METHOD: Focus group
      interviews were conducted with patients who were on long-term disability leave
      and had problems returning to the workforce. We asked them about the importance
      of the collaboration between occupational and curative physicians, and asked
      their opinions on what they believed these respective physicians' roles should
      be. RESULTS: Patients believe that securing support from their treating
      physicians when there are differences in opinion with their occupational
      physicians is the most important benefit of occupational-curative collaboration.
      For fear of potential negative consequences, they themselves want to exert as
      much control as possible on the exchange of information between their treating
      physicians and their occupational physicians. The patient primarily sees the
      treating physician as protector; the occupational physician supports the patient
      in reintegration by mediating between employee and company. CONCLUSION: A
      physician's predominant perspective of the cooperation between occupational and
      curative physicians is a clinical one; the emphasis being on the establishment of
      adequate diagnoses and their treatments. Patients, however, view the cooperation
      between their occupational and curative physicians from a strategic perspective
      in which their own interests are the key decisive factors. In daily practice,
      this might explain the reason behind patients being more reserved about
      occupational-curative cooperation, in comparison with physicians. It is advisable
      that patients not only be asked their consent, but that they are also granted a
      consciously active role in the collaboration between their occupational and
      curative physicians as well as in their own occupational reintegration process.

PMID- 22152416
TI  - [Doctor, may I travel in space? Aeromedical considerations regarding commercial
      suborbital space flights].
AB  - Within a few years, the first commercial operators will start flying passengers
      on suborbital flights to the verge of space. Medical data on the effects of space
      journeys on humans have mainly been provided by professional astronauts. There is
      very little research into the aeromedical consequences of suborbital flights for
      the health of untrained passengers. Low air pressure and oxygen tension can be
      compensated for by pressurising the spacecraft or pressure suit. Rapid changes in
      gravitational (G-)force pose ultimate challenges to cardiovascular adaptation
      mechanisms. Zero-gravity and G-force may cause motion sickness. Vibrations and
      noise during the flight may disturb communication between passengers and crew. In
      addition, the psychological impact of a suborbital flight should not be
      underestimated. There are currently no legal requirements available for medical
      examinations for commercial suborbital flights, but it seems justifiable to
      establish conditions for potential passengers' states of health.

PMID- 22152417
TI  - [Hypoglycaemia unawareness: judge driving ability prudently].
AB  - Several factors can influence the ability to drive by patients with diabetes
      mellitus. The most important factor would be hypoglycaemia. It seems logical that
      hypoglycaemia unawareness would be an important risk factor for accidents.
      However, in everyday practice, hypoglycaemia-related accidents are rare.
      Moreover, it seems that only a small subset of people with diabetes is
      responsible for the overall slightly elevated risk of car accidents. It appears
      that not hypoglycaemia unawareness itself is a risk factor, but primarily a
      history of previous hypoglycaemia-related accidents. Although ascertaining
      hypoglycaemia awareness currently seems the most suitable method for the
      assessment of driving ability, this may not be fair. In the future, we hope to
      have better methods of assessing the risk of accidents. Until that time, we
      should apply current law prudently, and mainly preclude from driving those
      diabetic patients who have experienced loss of consciousness or have needed
      outside help due to hypoglycaemia.

PMID- 22152418
TI  - Bowel ischemia in a baby with unspecified renovascular hypertension: a case
      report.

PMID- 22152419
TI  - [Patient oriented clinical studies after approval].

PMID- 22152420
TI  - [The relevance of head-to-head trials to patient-centred clinical research].
AB  - Head-to-head trials can contribute considerably to improving patient-centred
      care. To ensure that patients are optimally supplied with drugs and medical
      devices following market release, it is necessary to choose the best therapy from
      several options. The gold standard of efficacy comparisons is randomised head-to
      head studies comparing alternative methods. These trials establish the evidence
      base for choosing and excluding a treatment, which in turn improves the quality
      of health care services, even from an economic point of view. These trials are
      performed under high international quality standards of planning, conducting and
      reporting. Since comparative effectiveness research (CER) largely includes
      science-initiated investigations, all stakeholders should participate in the
      funding of these studies.

PMID- 22152421
TI  - [Bringing evidence to practice: obstacles and barriers].
AB  - Translating clinical research findings into daily medical practice is a complex
      procedure and subject to multiple impacts. Studies sponsored by drug
      manufacturers produce positive results more frequently than would be expected by
      chance alone; positive studies have a better chance to be published than negative
      ones. There is a lack of effective implementation strategies for medical
      guidelines. The mismatch of study population and own patients renders the
      generalizability of study results difficult. Other confounding factors in head-to
      head studies are drug comparisons that do not conform to the gold standard, non
      equivalent dosages and study duration. To solve these problems clinical research
      must pick up questions and problems from daily medical care. Studies independent
      of drug companies should be funded with public money, and health care research
      needs public support. Access to study protocols and data must be open to the
      public.

PMID- 22152422
TI  - [Closing evidence gaps].
AB  - The Federal Joint Committee (G-BA) is the paramount decision-making panel of the
      self-government body of service providers and health insurance funds. The G-BA
      commissions the Institute for Quality and Efficiency in Health Care (IQWiG) to
      conduct benefit assessments as one of the Institute's main tasks. Both
      organisations are regularly faced with "evidence gaps." These are situations
      where, on the one hand, a new medical technology is being propagated and pushed
      into the health care system, and on the other hand, no sufficiently reliable
      proof of benefit exists based on the methods of evidence-based medicine. It is
      possible to encourage closure of such evidence gaps by making "negative
      decisions" (meaning, for example, rejection of coverage for a certain
      intervention) but also by "conditional coverage decisions," whereby fluent
      transition is conceivable. Innovative ideas, such as a multilaterally financed
      research funds, are called for to sponsor clinical trials in those areas which
      are of little commercial interest.

PMID- 22152423
TI  - [Clinical trials in oncology: deficits and proposals for solution].
AB  - Various investigations have identified deficits in clinical studies conducted for
      the market authorisation of haematological and oncological drugs. Based on data
      from European Public Assessment Reports (EPAR) of the European Medicines Agency
      (EMA), an analysis of the quality of these studies, which serve as the basis of
      marketing authorisation of currently approved drugs, is showing improvement. For
      example, endpoints recommended by the EMA are frequently used. However, deficits
      of marketing authorisation studies are still noticeable, e. g., results based on
      unplanned interim analyses or post hoc subgroup analyses. In addition to the
      improved quality of studies prior to marketing authorisation, independent
      clinical studies need to be conducted after marketing authorisation has been
      obtained, a good example of which are therapy optimisation studies (TOS) in acute
      lymphatic leukaemia (ALL). A goal of TOS is the examination of multimodal therapy
      concepts in the real world context of routine clinical practice. They can supply
      valuable data for drug safety and long-term observation. In order to conduct post
      marketing authorisation studies, funding is required and bureaucratic hurdles
      associated with the 12(th) amendment to the Pharmaceutical Act will have to be
      reduced. The results of these studies are needed to efficiently handle limited
      health resources and to adequately inform and treat patients.

PMID- 22152424
TI  - [Size and quality of clinical research on non-medical interventions: a systematic
      analysis of IQWiG reports].
AB  - BACKGROUND: A sufficient number of randomised controlled clinical trials (RCTs)
      with high methodological reliability are required to allow a critical assessment
      of therapeutic interventions. The aim of this study was to evaluate the final
      reports of the Institute for Quality and Efficiency in Health Care (IQWiG)
      addressing non-medical interventions. These reports were analysed in order to
      determine how many endpoint-related comparisons were evaluated by clinical
      studies, how many by RCTs and how many by methodologically reliable RCTs.
      METHODS: Seventeen out of eighteen final reports of the IQWiG department of non
      medical interventions were critically analysed. The final reports had been
      generated from 2006 till 2009. Comparison of therapeutic procedures and patient
      relevant endpoints were taken from the final reports. Additional patient relevant
      endpoints were considered whenever these had been included in the result section.
      RCTs considered essential for the assessment were identified. RCTs obtaining the
      biometric rating no shortcomings, moderate shortcomings or low bias were
      considered to be of methodological reliability. RESULTS: A total of 537
      comparisons addressing single endpoints were identified. Clinical studies were
      available for 50% of these comparisons (n=272). For 38% of the comparisons
      (n=205) RCTs could be included, but in only 18% these RCTs had reliable methods.
      The number of reports containing zero, one, and more than one RCT was 6, 4, and
      7, respectively. Methodologically reliable RCTs were included in only 8 out of 17
      final reports. DISCUSSION: The analysis of evidence showed that both the number
      and the quality of studies were insufficient. This is why better standards for
      the evaluation of non-medical interventions need to be established. This may be
      achieved by raising the regulatory requirements and by intensifying research from
      independent institutions.

PMID- 22152425
TI  - [Reflections, ideas and initial approaches on the medical home concept].

PMID- 22152426
TI  - [Electronic networking and the central electronic medical record as structural
      organizational elements of regional interdisciplinary health care in healthy
      Kinzigtal].

PMID- 22152427
TI  - Effects of carbohydrates-BCAAs-caffeine ingestion on performance and
      neuromuscular function during a 2-h treadmill run: a randomized, double-blind,
      cross-over placebo-controlled study.
AB  - BACKGROUND: Carbohydrates (CHOs), branched-chain amino acids (BCAAs) and caffeine
      are known to improve running performance. However, no information is available on
      the effects of a combination of these ingredients on performance and
      neuromuscular function during running. METHODS: The present study was designed as
      a randomized double-blind cross-over placebo-controlled trial. Thirteen trained
      adult males completed two protocols, each including two conditions: placebo (PLA)
      and Sports Drink (SPD: CHOs 68.6 g.L-1, BCAAs 4 g.L-1, caffeine 75 mg.L-1).
      Protocol 1 consisted of an all-out 2 h treadmill run. Total distance run and
      glycemia were measured. In protocol 2, subjects exercised for 2 h at 95% of their
      lowest average speeds recorded during protocol 1 (whatever the condition).
      Glycemia, blood lactate concentration and neuromuscular function were determined
      immediately before and after exercise. Oxygen consumption (VO2), heart rate (HR)
      and rate of perceived exertion (RPE) were recorded during the exercise. Total
      fluids ingested were 2 L whatever the protocols and conditions. RESULTS: Compared
      to PLA, ingestion of SPD increased running performance (p = 0.01), maintained
      glycemia and attenuated central fatigue (p = 0.04), an index of peripheral
      fatigue (p = 0.04) and RPE (p = 0.006). Maximal voluntary contraction, VO2, and
      HR did not differ between the two conditions. CONCLUSIONS: This study showed that
      ingestion of a combination of CHOs, BCAAs and caffeine increased performance by
      about 2% during a 2-h treadmill run. The results of neuromuscular function were
      contrasted: no clear cut effects of SPD were observed. TRIAL REGISTRATION:
      ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT00799630.

PMID- 22152429
TI  - Effect of diffuse panbronchiolitis critical region 1 polymorphisms on the risk of
      aspirin-exacerbated respiratory disease in Korean asthmatics.
AB  - BACKGROUND: The functional role of the human diffuse panbronchiolitis critical
      region 1 (DPCR1) gene, located in the major histocompatibility complex class I,
      has not been widely investigated. However, this gene is a well known genetic
      marker for diffuse panbronchiolitis, a disease  affecting human respiratory
      bronchioles. In this study we explored the association between polymorphisms in
      DPCR1 and aspirin-exacerbated respiratory disease (AERD), an asthma phenotype.
      METHODS: Genotyping of 6 polymorphisms was carried out in a total of 189 Korean
      asthmatic patients stratified  into 93 AERD cases and 96 aspirin tolerant asthma
      controls. Subjects who exhibited significant decrease of FEV(1) by aspirin
      provocation were identified as AERD subjects. Logistic and regression analyses
      were performed to investigate the association between DPCR1 polymorphisms and 
      the risk of AERD as well as FEV(1) decline. RESULTS: Initial analysis revealed
      significant association of rs2517449 with AERD, with a P value of .03 via a
      recessive model; however, the association signal disappeared after multiple
      testing corrections. In addition, rs2517449  and rs2240804 also showed
      association signals with decline of FEV(1) after aspirin provocation (P = .007
      and .03, respectively, in a recessive model). After testing for multiple
      comparisons, only the association signal from rs2517449 was retained (P(corr)  =
      .04), while other polymorphisms showed no associations with the risk of AERD and
      FEV(1) decline. CONCLUSIONS: Our results show that polymorphisms in DPCR1 are not
      associated with the risk of AERD.

PMID- 22152428
TI  - Non-peptidergic small diameter primary afferents expressing VGluT2 project to
      lamina I of mouse spinal dorsal horn.
AB  - BACKGROUND: Unmyelinated primary afferent nociceptors are commonly classified
      into two main functional types: those expressing neuropeptides, and non
      peptidergic fibers that bind the lectin IB4. However, many small diameter primary
      afferent neurons neither contain any known neuropeptides nor bind IB4. Most
      express high levels of vesicular glutamate transporter 2 (VGluT2) and are assumed
      to be glutamatergic nociceptors but their terminations within the spinal cord are
      unknown. We used in vitro anterograde axonal tracing with Neurobiotin to identify
      the central projections of these putative glutamatergic nociceptors. We also
      quantitatively characterised the spatial arrangement of these terminals with
      respect to those that expressed the neuropeptide, calcitonin gene-related peptide
      (CGRP). RESULTS: Neurobiotin-labeled VGluT2-immunoreactive (IR) terminals were
      restricted to lamina I, with a medial-to-lateral distribution similar to CGRP-IR
      terminals. Most VGluT2-IR terminals in lateral lamina I were not labeled by
      Neurobiotin implying that they arose mainly from central neurons. 38 +/- 4% of
      Neurobiotin-labeled VGluT2-IR terminals contained CGRP-IR. Conversely, only 17 +/
      4% of Neurobiotin-labeled CGRP-IR terminals expressed detectable VGluT2-IR.
      Neurobiotin-labeled VGluT2-IR or CGRP-IR terminals often aggregated into small
      clusters or microdomains partially surrounding intrinsic lamina I neurons.
      CONCLUSIONS: The central terminals of primary afferents which express high levels
      of VGluT2-IR but not CGRP-IR terminate mainly in lamina I. The spatial
      arrangement of VGluT2-IR and CGRP-IR terminals suggest that lamina I neurons
      receive convergent inputs from presumptive nociceptors that are primarily
      glutamatergic or peptidergic. This reveals a previously unrecognized level of
      organization in lamina I consistent with the presence of multiple nociceptive
      processing pathways.

PMID- 22152430
TI  - Meat and milk intakes and toddler growth: a comparison feeding intervention of
      animal-source foods in rural Kenya.
AB  - OBJECTIVE: To examine the effects of animal-source foods on toddler growth.
      DESIGN: A 5-month comparison feeding intervention study with one of three millet
      based porridges randomized to eighteen feeding stations serving 303 children aged
      11-40 months. Feeding stations served plain millet porridge (Plain group),
      porridge with milk (Milk group) or porridge with beef (Meat group).
      Anthropometry, morbidity and food intake were measured at baseline and regular
      intervals. Longitudinal mixed models were used to analyse growth. SETTING: Embu,
      Kenya. SUBJECTS: Two hundred and seventy-four children were included in final
      analyses. RESULTS: Linear growth was significantly greater for the Milk group
      than the Meat group (P = 0.0025). Slope of growth of mid-arm muscle area of the
      Plain group was significantly greater than in the Meat group (P = 0.0046), while
      the Milk group's mid-upper arm circumference growth rate was significantly
      greater than the Meat group's (P = 0.0418). The Milk and Plain groups' measures
      did not differ. CONCLUSIONS: Milk and meat porridges did not have a significantly
      greater effect on growth than plain porridge in this undernourished population.
      Linear growth was influenced by more than energy intakes, as the Plain group's
      total body weight-adjusted energy intakes were significantly greater than the
      Meat group's, although linear growth did not differ. Energy intakes may be more
      important for growth in arm muscle. The diverse age distribution in the study
      makes interpretation difficult. A longer study period, larger sample size and
      more focused age group would improve clarity of the results.

PMID- 22152431
TI  - Attention deficit hyperactivity disorder (ADHD): from a childhood
      neuropsychiatric disorder to an adult condition.

PMID- 22152432
TI  - Assessing self-awareness of dyskinesias in Parkinson's disease through movie
      materials.
AB  - The aim of our study was to determine self-awareness of dyskinesias and other
      core motor symptoms in Parkinson's disease (PD) through the use of movie
      presentations. A scale based on 10 movies (five depicting dyskinesias and five
      showing core symptoms) and the Self-Assessment Parkinson's Disease Disability
      Scale were administered to 21 patients (all with a Mini-Mental State Examination 
      MMSE score >= 25). Neurological assessment included the Unified Parkinson's
      Disease Rating Scale and the Hoehn-Yahr and Schwab-England scales. In addition,
      the MMSE, Beck Depression Inventory and Stroop task were administered. Overall,
      patient and caregiver ratings of dyskinesias and core PD symptoms were
      consistent. Two patients (9%) completely denied dyskinesias, while four patients
      (19%) significantly underestimated their dyskinesias. Our results confirm that
      poor self-awareness of symptoms in PD may be selective and that denial of
      dyskinesias affects only a minority of patients with normal cognitive status
      (MMSE >= 25). Most patients are aware of the presence of dyskinesias. Poor self
      awareness of dyskinesias is associated with longer disease duration.

PMID- 22152433
TI  - Alexithymia may modulate decision making in patients with de novo Parkinson's
      disease.
AB  - The aim of this study was to investigate whether and how alexithymia may
      influence decision making under conditions of uncertainty, assessed using the
      Iowa Gambling Task, in patients with newly diagnosed, untreated (de novo)
      Parkinson's disease, as previously reported for healthy subjects. Twenty-four
      patients with de novo Parkinson's disease underwent a neuropsychological and
      neuropsychiatric assessment, including the Toronto Alexithymia Scale, the
      Geriatric Depression Scale Short Form, and the Iowa Gambling Task (IGT). The
      assessment showed that 12 patients were alexithymic and 12 were non-alexithymic;
      seven patients were found to be mildly depressed and 17 non-depressed.
      Alexithymic and non-alexithymic patients did not differ in the IGT total score;
      however, significant differences emerged across the third block of the IGT, in
      which the alexithymic patients outperformed the nonalexithymic patients.
      Depression did not influence IGT performance. Alexithymia may modulate decision
      making, as assessed with the IGT; alexithymia could be associated with faster
      learning to avoid risky choices and negative feedback, as previously reported in
      some studies conducted in anxious or depressed patients.

PMID- 22152434
TI  - Effect of prior medical treatments on ischemic stroke severity and outcome.
AB  - Antiplatelets, antihypertensives, and statins might reduce the severity of the
      event or improve outcome in patients who, despite prior medical treatment, have a
      stroke. We evaluated, in patients who had an ischemic stroke, the effect, on
      stroke severity and outcome, of prior treatment with antiplatelets,
      antihypertensives, and statins, used either alone or in a three-drug combination.
      Stroke in Italy and Related Impact on Outcome (SIRIO) was a prospective,
      nationwide, multicenter, hospital-based, observational study that included
      patients aged.18 years with acute ischemic stroke. We studied 2,529 acute
      ischemic stroke patients from the SIRIO population: 887 were antiplatelet users,
      1,497 antihypertensive users, 231 statin users, and 138 three-drug combination
      users prior to the index event. The adjusted logistic regression analysis showed
      an association between prior treatment with statins and good functional outcome
      at discharge, while prior treatment with antiplatelets, antihypertensives or the
      three-drug combination did not influence severity or outcome. The absolute
      probability of a good functional outcome was 46.3% (95% CI: 40.3%-53.2%) in
      statin users and 36.7% (95% CI: 34.7%-38.7%) in non-users of statins; the
      absolute risk difference was 9.6% (95% CI: 2.9%-16.4%; p=0.004). Prior treatment
      with antiplatelets, antihypertensives, or the three-drug combination did not
      influence stroke severity or outcome, while prior treatment with statins did not
      influence stroke severity but was associated with a better functional outcome.

PMID- 22152435
TI  - Changes in muscle activity determine progression of clinical symptoms in patients
      with chronic spine-related muscle pain. A complex clinical and neurophysiological
      approach.
AB  - Spine-related muscle pain can affect muscle strength and motor unit activity.
      This study was undertaken to investigate whether surface electromyographic (sEMG)
      recordings performed during relaxation and maximal contraction reveal differences
      in the activity of muscles with or without trigger points (TRPs). We also
      analyzed the possible coexistence of characteristic spontaneous activity in
      needle electromyographic (eEMG) recordings with the presence of TRPs. Thirty
      patients with non-specific cervical and back pain were evaluated using clinical,
      neuroimaging and electroneurographic examinations. Muscle pain was measured using
      a visual analog scale (VAS), and strength using Lovett's scale; trigger points
      were detected by palpation. EMG was used to examine motor unit activity. Trigger
      points were found mainly in the trapezius muscles in thirteen patients. Their
      presence was accompanied by increased pain intensity, decreased muscle strength,
      increased resting sEMG amplitude, and decreased sEMG amplitude during muscle
      contraction. eEMG revealed characteristic asynchronous discharges in TRPs. The
      results of EMG examinations point to a complexity of muscle pain that depends on
      progression of the myofascial syndrome.

PMID- 22152436
TI  - The autistic phenotype in Down syndrome: differences in adaptive behaviour versus
      Down syndrome alone and autistic disorder alone.
AB  - The autistic phenotype in Down syndrome (DS) is marked by a characteristic
      pattern of stereotypies, anxiety and social withdrawal. Our aim was to study
      adaptive behaviour in DS with and without autistic comorbidity using the Vineland
      Adaptive Behaviour Scales (VABS), the Childhood Autism Rating Scales (CARS) and
      the DSM IV-TR criteria. We assessed 24 individuals and established three groups:
      Down syndrome (DS), DS and autistic disorder (DS-AD), and autistic disorder (AD).
      The DS and DS-AD groups showed statistically significantly similar strengths on
      the VABS (in receptive and domestic skills). The DS and DS-AD subjects also
      showed similar strengths on the CARS (in imitation and relating), differing
      significantly from the AD group. The profile of adaptive functioning and symptoms
      in DS-AD seemed to be more similar to that found in DS than to the profile
      emerging in AD. We suggest that the comorbidity of austistic symptoms in DS
      hampered the acquisition of adaptive skills more than did the presence of DS
      alone.

PMID- 22152437
TI  - No auditory conduction abnormality in children with attention deficit
      hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral
      developmental disorder characterized by lack of sustained attention and
      hyperactivity. It has been suggested that asymmetrical conduction of the auditory
      stimulus in the brainstem plays a role in the pathophysiological process of ADHD.
      In the present study, the functional integrity of the central auditory pathway
      was assessed using the auditory brainstem response (ABR), mid-latency response
      (MLR) and slow vertex response (SVR). Twenty ADHD children and twenty controls
      were recruited for the study and recordings were done on a computerized evoked
      potential recorder using the 10-20 system of electrode placement. There emerged
      no significant difference in absolute peak latencies, interpeak latencies and
      amplitude of ABR or latency of MLR in the ADHD children as compared with the
      controls. Prolongation of the SVR latency was found in the children with ADHD
      versus the controls, but the difference was statistically insignificant. The
      present study does not suggest any auditory conduction abnormality as a
      contributory factor in ADHD.

PMID- 22152438
TI  - Tension-type headache: one or more headaches?
AB  - In this context, the focus will be on the homogeneity of tension-type headache (T
      TH): is it a disease? Or: is it more likely to be a syndrome? A multiplicity of
      disorders from as drastically different fields of medicine as disorders caused by
      environmental gases, intra-psychic conflicts, and nuchal/cervical disorders can
      putatively fake T-TH. T-TH is in all probability a conglomerate of disorders and
      not one solid, homogeneous disorder.

PMID- 22152439
TI  - Source attribution of human salmonellosis using a meta-analysis of case-control
      studies of sporadic infections.
AB  - Salmonella is an important cause of human illness. Disease is frequently
      associated with foodborne transmission, but other routes of exposure are
      recognized. Identifying sources of disease is essential for prioritizing public
      health interventions. Numerous case-control studies of sporadic salmonellosis
      have been published, often using different methodologies and settings. Systematic
      reviews consist of a formal process for literature review focused on a research
      question. With the objective of identifying the most important risk factors for
      salmonellosis, we performed a systematic review of case-control studies and a
      meta-analysis of obtained results. Thirty-five Salmonella case-control studies
      were identified. In the meta-analysis, heterogeneity between studies and possible
      sources of bias were investigated, and pooled odds ratios estimated. Results
      suggested that travel, predisposing factors, eating raw eggs, and eating in
      restaurants were the most important risk factors for salmonellosis. Sub-analyses
      by serotype were performed when enough studies were available.

PMID- 22152440
TI  - The ability to act--multiple suicidal gunshot wounds.
AB  - Multiple self-inflicted gunshot wounds are rare and usually present a challenge
      to the forensic pathologist in determining the manner of death. Determining a
      person's capability to act following a gunshot wound can be of major importance
      in crime scene reconstruction and in differentiation between homicide and
      suicide. Questions concerning the possibility of physical activity following a
      given gunshot wound are repeatedly raised in court. We report herein three
      unusual cases of suicide involving multiple gunshot wounds; all the victims
      suffered gunshot wounds of the head without immediate incapacitation. In the
      first two cases, the head was target for two gunshots. Third case was a
      combination of two gunshots to the head and chest. In the text, we focus on the
      victim's ability to act after the first shot, with regards to the character and
      localization of the gunshot wound. Also, we focus on findings that are typical
      for a repeated suicidal shot.

PMID- 22152441
TI  - Excited delirium syndrome (ExDS): redefining an old diagnosis.
AB  - Recently, the National Institute of Justice (NIJ) of the United States of America
      convened a meeting of experts in the area of Excited Delirium Syndrome (ExDS).
      The history of ExDS, the clinical presentation, the pathophysiology, differential
      diagnoses and management options were discussed. Though the specific
      pathophysiological pathways of ExDS have yet to be formally defined, considerable
      research has been undertaken on this topic. It is important for law enforcement,
      medical and other healthcare professionals to be familiar with current knowledge
      about the syndrome. This paper summarizes the current state and knowledge of
      ExDS.

PMID- 22152442
TI  - An autopsy study of coronary atherosclerosis and its relation to anthropometric
      measurements/indices of overweight and obesity in men.
AB  - Atherosclerosis accounts for a large proportion of cardiovascular system
      associated morbidity and mortality. The present autopsy based study is aimed to
      study the correlation between coronary atherosclerosis and anthropometric
      measurements/indices of overweight and obesity such as; Waist Circumference (WC),
      Hip Circumference (HC), Body Mass Index (BMI), and Waist Hip Ratio (WHR) in men
      from southern India. The present research also analyses the correlation between
      anthropometric measurements/indices of overweight and obesity in men with number
      of coronaries affected with atherosclerosis in individuals. The study included 50
      autopsies conducted in the Government District Wenlock Hospital, Mangalore during
      March and September 2008. The heart was dissected following standard autopsy
      protocol and a 5 cm section of the right coronary artery (RCA) in the atrio
      ventricular groove from its origin, a 5 cm segment of the left anterior
      descending artery (LADA) distal to the origin of the circumflex artery, but
      including the region of origin of the circumflex branch and left coronary artery
      (LCA) from its origin till the circumflex branch were excised, dissected out,
      fixed in 10% formalin, marked for identification and sent for histopathological
      analysis. The study shows a positive correlation of WC and WHR with
      atherosclerotic changes in the RCA. The number of arteries affected with
      atherosclerosis is found to be well correlated with WC, BMI and WHR. The study
      confirms an association between anthropometric measurements/indices of obesity,
      grade of atherosclerosis in the RCA and the number of arteries affected with
      atherosclerosis. Anthropometric measurements/indices of obesity can be an
      effective means to identify high risk cases of atherosclerosis at an early stage
      that can be effective in reducing the associated cardiac morbidity and mortality.

PMID- 22152443
TI  - Relation between fingerprints and different blood groups.
AB  - Fingerprint is one of the oldest, reliable and mature biometric technologies and
      is considered one of the best, cheapest and legitimate proofs of identification.
      A correlation between physical characteristics like fingerprints and blood group
      was demonstrated in previous studies. This study was carried out in 2010 on 305
      Libyan medical students of Al-Jabal Al-Gharbi, University, Zawia, Libya and were
      selected randomly having different ABO blood groups, with the objective to a)
      Study distribution of fingerprint pattern among the subjects having different ABO
      and Rh blood group b) Correlate any relation between their characters and blood
      group. The data from the study showed that male: female ratio was 1.2:1. Majority
      of subjects (48.9%) in this study were of blood group O followed by blood group A
      (33.1%), B (12.8%) and AB (5.2%). Rh-positive cases constitute about 87.2% of all
      studied cases. The general distribution of pattern of finger showed high
      frequency of Loops registering 50.5%; followed by whorls (35.1%) and arches
      (14.4%). In Rh+ve cases of blood group A and O loops incidences were the highest
      (52% and 54.3% respectively) then whorls (33.4% and 30.6% respectively), while in
      blood group B whorls were predominance in both Rh+ve and Rh-ve cases. In all
      blood groups there were high frequency of loops in thumb, index and little
      fingers.

PMID- 22152444
TI  - Dental age assessment (DAA): a study of a Caucasian population at the 13 year
      threshold.
AB  - The purpose of this study was to develop a Reference Data Set for Dental Age
      Assessment at the 13 year old threshold in Caucasian children. PATIENTS,
      MATERIALS AND METHODS: The Reference Data Set comprised 5187 re-used Dental
      Panoramic Tomographs (DPTs) between the ages of 11-15 years, from both the
      Eastman Dental Hospital and King's College Dental Hospital archives. Tooth
      Development Stages were recorded for the left maxillary and mandibular teeth and
      all four permanent third molars (Demirjian et al., 1973, Demirjian 1978). A
      separate Study Sample of DPTs, comprising 50 males and 50 females aged between 10
      and 16 years was collected to test the accuracy of the method. Summary Data was
      generated for the individual Tooth Development Stages which consisted of the
      number (n-tds), mean (x), standard deviation (sd) and the standard error (se). By
      using the mathematical techniques of meta-analysis, this data was used to
      estimate the age of each subject in the Study Sample. The estimated Dental Age
      derived was compared to the gold standard of Chronological Age. RESULTS: The mean
      difference between the Chronological Age and Dental Age was determined to be -0.1
      years (-1.2 months) for males and 0.05 years (-0.6 months) for females.
      CONCLUSION: Dental Age was reliably estimated at the 13 year threshold.

PMID- 22152445
TI  - Electroencephalographic abnormalities in antisocial personality disorder.
AB  - The presence of brain dysfunction in violent offenders has been frequently
      examined with inconsistent results. The aim of the study was to assess the EEG of
      84 violent offenders by visual inspection and frequency-domain quantitative
      analysis in 84 violent prisoners. Low-resolution electromagnetic tomography
      (LORETA) was also employed for theta band of the EEG spectra. Antisocial
      personality disorder (ASPD) was present in 50 of the offenders and it was absent
      in the remaining 34. The prevalence of EEG abnormalities, by visual inspection,
      was similar for both the ASPD group (82%) and non-ASPD group (79%). The brain
      topography of these anomalies also did not differ between groups, in contrast to
      results of the EEG quantitative analysis (QEEG) and LORETA that showed remarkable
      regional differences between both groups. QEEG analysis showed a pattern of
      excess of theta-delta activities and decrease of alpha band on the right fronto
      temporal and left temporo-parietal regions in the ASPD group. LORETA signified an
      increase of theta activity (5.08 Hz) in ASPD group relative to non-ASPD group
      within left temporal and parietal regions. Findings indicate that QEEG analysis
      and techniques of source localization may reveal differences in brain electrical
      activity among offenders with ASPD, which was not obvious to visual inspection.

PMID- 22152446
TI  - Psychological profiles of adult sexual assault victims.
AB  - This is a retrospective analysis of the psychological and psychiatric history of
      adult patients who attended the Lancashire Sexual Assault and Forensic
      Examination Centre between April 1st 2010 and March 31st 2011 for forensic
      examination. During this time 269 adults attended for forensic examination; the
      records of these patients were audited for evidence of psychological or
      psychiatric ill health. Affective disorders were disclosed in 48.7% of cases
      (depression, depression and anxiety, anxiety, bipolar affective disorder) and
      3.0% declared having been diagnosed with a psychotic illness (schizophrenia,
      psychotic illness, psychotic behaviour). Furthermore, deliberate self-harm was
      disclosed by 29.4% of complainants and 22.3% of attendees had attempted suicide
      at least once in their lifetime. This study highlights increased prevalence of
      mental illness in sexual assault complainants which contributes to increased
      states of vulnerability. This and further similar research efforts have a role to
      influence prevention schemes, management strategies and healthcare planning for
      those individuals who are sexually assaulted.

PMID- 22152447
TI  - Strychnine in amoxicillin capsules: a means of homicide.
AB  - Fatal strychnine poisoning is uncommon. It is no longer used as a therapeutic
      drug and its availability to the public is controlled by legislations in various
      jurisdictions, but it is still in use as a rodenticide and an adulterant in
      street drugs. Homicide by strychnine is extremely rare. As the autopsy findings
      are subtle, strychnine poisoning could easily be overlooked and a homicide may go
      undetected. This communication highlights an unusual case of homicide by
      strychnine. It is important that in deaths where there are no gross autopsy
      findings, sudden death in particular, that routine toxicology be performed, in
      which strychnine is likely to be detected.

PMID- 22152448
TI  - Gunshot wound in skeletonised human remains with partial adipocere formation.
AB  - We present a case of skeletonised human remains. In the present case report, a
      body was exhumed from the ground above a cemetery. On exhumation, the body was
      partially-skeletonised with adipocere formation on the upper part of the body.
      Autopsy of the body showed two bullets in the right thigh muscle and lumbar
      vertebrae between L4 and L5. Postmortem changes and destruction of soft tissue
      made it impossible to determine direction of fire through the body, even in a
      careful complete autopsy.

PMID- 22152449
TI  - Blunt trauma to the chest--a case of delayed cardiac rupture.
AB  - Blunt traumatic cardiac rupture is a relatively uncommon diagnosis and is usually
      associated with a high mortality rate. A case of delayed cardiac rupture is
      described in an elderly person who sustained blunt chest trauma following a fall
      into a roadside ditch. In the case reported herein, the preliminary
      investigations at the time of admission did not show any evidence of
      haemopericardium. The patient deteriorated suddenly, possibly due to a delayed
      rupture of the right ventricle that was diagnosed postmortem. Acute cardiac
      tamponade resulting from rupture of the right ventricle is a serious and life
      threatening state. A high index of suspicion about the possibility of delayed
      cardiac rupture is required during the management of a case of polytrauma where
      significant cardiac findings can be masked by the presence of other injuries.

PMID- 22152450
TI  - My experience of the DFCASA exam including recommendations to potential
      candidates.
AB  - My experience of the new Diploma in the Forensic and Clinical aspects of Sexual
      Assault and how this could be used as guidance for future candidates.

PMID- 22152453
TI  - Bioethics and plumbing.

PMID- 22152452
TI  - Genetic variation among Clonorchis sinensis isolates from different geographic
      regions in China revealed by sequence analyses of four mitochondrial genes.
AB  - The present study examined sequence variation in four mitochondrial (mt) genes,
      namely cytochrome c oxidase subunits 1 (cox1) and 2 (cox2), and NADH
      dehydrogenase subunits 1 and 2 (nad1 and nad2) among Clonorchis sinensis isolates
      from different endemic regions in China, and their phylogenetic relationships
      with other zoonotic trematodes were reconstructed. A portion of the cox1 and cox2
      genes (pcox1 and pcox2), and nad1 and nad2 genes (pnad1 and pnad2) were amplified
      separately from individual liver flukes by polymerase chain reaction (PCR) and
      the amplicons were subjected to sequencing from both directions. The intra
      specific sequence variations within C. sinensis were 0-1.6% for pcox1, 0-1.4% for
      pcox2, 0-0.9% for pnad1 and 0-1.0% for pnad2. Phylogenetic analyses based on the
      combined sequences of pcox1, pcox2, pnad1 and pnad2 revealed that all the C.
      sinensis isolates grouped together and were closely related to Opisthorchis
      felineus. These findings revealed the existence of intra-specific variation in
      mitochondrial DNA (mtDNA) sequences among C. sinensis isolates from different
      geographic regions, and demonstrated that mtDNA sequences provide reliable
      genetic markers for phylogenetic studies of zoonotic trematodes.

PMID- 22152451
TI  - High-fat diet accelerates progression of osteoarthritis after
      meniscal/ligamentous injury.
AB  - INTRODUCTION: Increasing obesity and type 2 diabetes, in part due to the high-fat
      (HF) Western diet, parallels an increased incidence of osteoarthritis (OA). This
      study was undertaken to establish a causal relation between the HF diet and
      accelerated OA progression in a mouse model and to determine the relative roles
      of weight gain and metabolic dysregulation in this progression. METHODS: Five
      week-old C57BL/6 mice were placed on HF (60% kcal) or low-fat (lean, 10% kcal)
      diets for 8 or 12 weeks before transecting the medial collateral ligament and
      excising a segment of the medial meniscus of the knee to initiate OA. One group
      was switched from lean to HF diet at the time of surgery. RESULTS: Body weight of
      mice on the HF diet peaked at 45.9 +/- 2.1 g compared with 29.9 +/- 1.8 g for
      lean diets, with only those on the HF becoming diabetic. Severity of OA was
      greater in HF mice, evidenced by the Osteoarthritis Research Society
      International (OARSI) histopathology initiative scoring method for mice and
      articular cartilage thickness and area. To assess the importance of weight gain,
      short- and long-term HF diets were compared with the lean diet. Short- and long
      term HF groups outweighed lean controls by 6.2 g and 20.5 g, respectively. Both
      HF groups became diabetic, and OA progression, evidenced by increased OARSI
      score, decreased cartilage thickness, and increased osteophyte diameter, was
      comparably accelerated relative to those of lean controls. CONCLUSIONS: These
      results demonstrate that the HF diet accelerates progression of OA in a type 2
      diabetic mouse model without correlation to weight gain, suggesting that
      metabolic dysregulation is a comorbid factor in OA-related cartilage
      degeneration.

PMID- 22152454
TI  - Whoopie pies, supersized fries. "Just" snacking? "Just" des(s)erts?

PMID- 22152455
TI  - "Please don't tell me". The right not to know.

PMID- 22152456
TI  - Terminal suffering and the ethics of palliative sedation.

PMID- 22152457
TI  - In defense of broad consent.

PMID- 22152458
TI  - Privacy versus history. How far should the dead hand reach?

PMID- 22152459
TI  - On the very idea of genetic justice. Why Farrelly's pluralistic prioritarianism
      cannot tackle genetic complexity.

PMID- 22152460
TI  - Research priorities and the future of pregnancy.

PMID- 22152461
TI  - In defense of ectogenesis.

PMID- 22152462
TI  - From pioneers to professionals.

PMID- 22152463
TI  - My bioethics journey.

PMID- 22152464
TI  - Fate or free will: my passage to bioethics.

PMID- 22152465
TI  - My problems with the B-word.

PMID- 22152466
TI  - A woman (and man) without a country.

PMID- 22152467
TI  - Crossing invisible lines.

PMID- 22152468
TI  - The road less traveled.

PMID- 22152469
TI  - A morning-induced, phosphorylation-gated repressor times evening gene expression:
      a new way for circadian clocks to use an old trick.
AB  - In this issue of Molecular Cell, Sancar et al. (2011) show that a morning-induced
      transcriptional repressor with a phosphorylation-gated half-life is a key cog in
      driving evening gene expression, adding new insights into how circadian clocks
      achieve phase-specific gene expression.

PMID- 22152470
TI  - Cdh1 is a HECT of an activator.
AB  - Cdh1 is a well-established activator of APC/C, a RING-type ubiquitin ligase. In
      this issue of Molecular Cell, Wan et al. (2011) report an APC/C-independent role
      of Cdh1 during development as an activator for Smurf1, a HECT-type ubiquitin
      ligase.

PMID- 22152471
TI  - Regulation of ribonucleotide reductase during iron limitation.
AB  - In this issue of Molecular Cell, Sanvisens et al. (2011) report a new mechanism
      for regulation of yeast ribonucleotide reductase activity that occurs during iron
      deprivation.

PMID- 22152472
TI  - A date with telomerase: pick you up at S phase.
AB  - Using the MS2 system for labeling mRNA, in this issue, Gallardo et al. (2011)
      find that telomere lengthening depends on a stable accumulation of multiple
      telomerase complexes in late S phase and that this process is temporally
      regulated by Rif1/2 proteins.

PMID- 22152473
TI  - A global circadian repressor controls antiphasic expression of metabolic genes in
      Neurospora.
AB  - The white-collar complex (WCC), the core transcription factor of the circadian
      clock of Neurospora, activates morning-specific expression of the transcription
      repressor CSP1. Newly synthesized CSP1 exists in a transient complex with the
      corepressor RCM1/RCO1 and the ubiquitin ligase UBR1. CSP1 is rapidly
      hyperphosphorylated and degraded via UBR1 and its ubiquitin conjugase RAD6. Genes
      controlled by CSP1 are rhythmically expressed and peak in the evening (i.e., in
      antiphase to morning-specific genes directly controlled by WCC). Rhythmic
      expression of these second-tier genes depends crucially on phosphorylation and
      rapid turnover of CSP1, which ensures tight coupling of CSP1 abundance and
      function to the circadian activity of WCC. Negative feedback of CSP1 on its own
      transcription buffers the amplitude of CSP1-dependent oscillations against
      fluctuations of WCC activity. CSP1 predominantly regulates genes involved in
      metabolism. It controls ergosterol synthesis and fatty acid desaturases and
      thereby modulates the lipid composition of membranes.

PMID- 22152474
TI  - The autophagy protein Atg12 associates with antiapoptotic Bcl-2 family members to
      promote mitochondrial apoptosis.
AB  - Autophagy and apoptosis constitute important determinants of cell fate and engage
      in a complex interplay in both physiological and pathological settings. The
      molecular basis of this crosstalk is poorly understood and relies, in part, on
      "dual-function" proteins that operate in both processes. Here, we identify the
      essential autophagy protein Atg12 as a positive mediator of mitochondrial
      apoptosis and show that Atg12 directly regulates the apoptotic pathway by binding
      and inactivating prosurvival Bcl-2 family members, including Bcl-2 and Mcl-1. The
      binding occurs independently of Atg5 or Atg3 and requires a unique BH3-like motif
      in Atg12, characterized by interaction studies and computational docking. In
      apoptotic cells, knockdown of Atg12 inhibited Bax activation and cytochrome c
      release, while ectopic expression of Atg12 antagonized the antiapoptotic activity
      of Mcl-1. The interaction between Atg12 and Bcl-2 family members may thus
      constitute an important point of convergence between autophagy and apoptosis in
      response to specific signals.

PMID- 22152475
TI  - Homeostatic control of mitotic arrest.
AB  - The spindle assembly checkpoint (SAC) restricts mitotic exit to cells that have
      completed chromosome-microtubule attachment. Cdc20 is a bifunctional protein. In
      complex with SAC proteins Mad2, BubR1, and Bub3, Cdc20 forms the mitotic
      checkpoint complex (MCC), which binds the anaphase-promoting complex (APC/C) and
      inhibits its mitotic exit-promoting activity. When devoid of SAC proteins, Cdc20
      serves as an APC/C coactivator and promotes mitotic exit. During mitotic arrest,
      Cdc20 is continuously degraded via ubiquitin-dependent proteolysis and
      resynthesized. It is believed that this cycle keeps the levels of Cdc20 below a
      threshold above which Cdc20 would promote mitotic exit. We report that
      p31(comet), a checkpoint antagonist, is necessary for mitotic destabilization of
      Cdc20. p31(comet) depletion stabilizes the MCC, super-inhibits the APC/C, and
      delays mitotic exit, indicating that Cdc20 proteolysis in prometaphase opposes
      the checkpoint. Our studies reveal a homeostatic network in which checkpoint
      sustaining and -repressing forces oppose each other during mitotic arrest and
      suggest ways for enhancing the sensitivity of cancer cells to antitubulin
      chemotherapeutics.

PMID- 22152476
TI  - Cdh1 regulates osteoblast function through an APC/C-independent modulation of
      Smurf1.
AB  - The APC/Cdh1 E3 ubiquitin ligase plays an essential role in both mitotic exit and
      G1/S transition by targeting key cell-cycle regulators for destruction. There is
      mounting evidence indicating that Cdh1 has other functions in addition to cell
      cycle regulation. However, it remains unclear whether these additional functions
      depend on its E3 ligase activity. Here, we report that Cdh1, but not Cdc20,
      promotes the E3 ligase activity of Smurf1. This is mediated by disruption of an
      autoinhibitory Smurf1 homodimer and is independent of APC/Cdh1 E3 ligase
      activity. As a result, depletion of Cdh1 leads to reduced Smurf1 activity and
      subsequent activation of multiple downstream targets, including the MEKK2
      signaling pathway, inducing osteoblast differentiation. Our studies uncover a
      cell-cycle-independent function of Cdh1, establishing Cdh1 as an upstream
      component that governs Smurf1 activity. They further suggest that modulation of
      Cdh1 is a potential therapeutic option for treatment of osteoporosis.

PMID- 22152477
TI  - Structural instability tuning as a regulatory mechanism in protein-protein
      interactions.
AB  - Protein-protein interactions mediate a vast number of cellular processes. Here,
      we present a regulatory mechanism in protein-protein interactions mediated by
      finely tuned structural instability and coupled with molecular mimicry. We show
      that a set of type III secretion (TTS) autoinhibited homodimeric chaperones adopt
      a molten globule-like state that transiently exposes the substrate binding site
      as a means to become rapidly poised for binding to their cognate protein
      substrates. Packing defects at the homodimeric interface stimulate binding,
      whereas correction of these defects results in less labile chaperones that give
      rise to nonfunctional biological systems. The protein substrates use structural
      mimicry to offset the weak spots in the chaperones and to counteract their
      autoinhibitory conformation. This regulatory mechanism of protein activity is
      evolutionarily conserved among several TSS systems and presents a lucid example
      of functional advantage conferred upon a biological system by finely tuned
      structural instability.

PMID- 22152478
TI  - Reconsidering movement of eukaryotic mRNAs between polysomes and P bodies.
AB  - Cell survival in changing environments requires appropriate regulation of gene
      expression, including posttranscriptional regulatory mechanisms. From reporter
      gene studies in glucose-starved yeast, it was proposed that translationally
      silenced eukaryotic mRNAs accumulate in P bodies and can return to active
      translation. We present evidence contradicting the notion that reversible storage
      of nontranslating mRNAs is a widespread and general phenomenon. First, genome
      wide measurements of mRNA abundance, translation, and ribosome occupancy after
      glucose withdrawal show that most mRNAs are depleted from the cell coincident
      with their depletion from polysomes. Second, only a limited subpopulation of
      translationally repressed transcripts, comprising fewer than 400 genes, can be
      reactivated for translation upon glucose readdition in the absence of new
      transcription. This highly selective posttranscriptional regulation could be a
      mechanism for cells to minimize the energetic costs of reversing gene-regulatory
      decisions in rapidly changing environments by transiently preserving a pool of
      transcripts whose translation is rate-limiting for growth.

PMID- 22152479
TI  - Regulation of ribonucleotide reductase in response to iron deficiency.
AB  - Ribonucleotide reductase (RNR) is an essential enzyme required for DNA synthesis
      and repair. Although iron is necessary for class Ia RNR activity, little is known
      about the mechanisms that control RNR in response to iron deficiency. In this
      work, we demonstrate that yeast cells control RNR function during iron deficiency
      by redistributing the Rnr2-Rnr4 small subunit from the nucleus to the cytoplasm.
      Our data support a Mec1/Rad53-independent mechanism in which the iron-regulated
      Cth1/Cth2 mRNA-binding proteins specifically interact with the WTM1 mRNA in
      response to iron scarcity and promote its degradation. The resulting decrease in
      the nuclear-anchoring Wtm1 protein levels leads to the redistribution of the Rnr2
      Rnr4 heterodimer to the cytoplasm, where it assembles as an active RNR complex
      and increases deoxyribonucleoside triphosphate levels. When iron is scarce, yeast
      selectively optimizes RNR function at the expense of other non-essential iron
      dependent processes that are repressed, to allow DNA synthesis and repair.

PMID- 22152480
TI  - FOXP3 orchestrates H4K16 acetylation and H3K4 trimethylation for activation of
      multiple genes by recruiting MOF and causing displacement of PLU-1.
AB  - Both H4K16 acetylation and H3K4 trimethylation are required for gene activation.
      However, it is still largely unclear how these modifications are orchestrated by
      transcriptional factors. Here, we analyzed the mechanism of the transcriptional
      activation by FOXP3, an X-linked suppressor of autoimmune diseases and cancers.
      FOXP3 binds near transcriptional start sites of its target genes. By recruiting
      MOF and displacing histone H3K4 demethylase PLU-1, FOXP3 increases both H4K16
      acetylation and H3K4 trimethylation at the FOXP3-associated chromatins of
      multiple FOXP3-activated genes. RNAi-mediated silencing of MOF reduced both gene
      activation and tumor suppression by FOXP3, while both somatic mutations in
      clinical cancer samples and targeted mutation of FOXP3 in mouse prostate
      epithelial cells disrupted nuclear localization of MOF. Our data demonstrate a
      pull-push model in which a single transcription factor orchestrates two
      epigenetic alterations necessary for gene activation and provide a mechanism for
      somatic inactivation of the FOXP3 protein function in cancer cells.

PMID- 22152481
TI  - p50 (NF-kappaB1) is an effector protein in the cytotoxic response to DNA
      methylation damage.
AB  - The functional significance of the signaling pathway induced by O(6)
      methylguanine (O(6)-MeG) lesions is poorly understood. Here, we identify the p50
      subunit of NF-kappaB as a central target in the response to O(6)-MeG and
      demonstrate that p50 is required for S(N)1-methylator-induced cytotoxicity. In
      response to S(N)1-methylation, p50 facilitates the inhibition of NF-kappaB
      regulated antiapoptotic gene expression. Inhibition of NF-kappaB activity is
      noted to be an S phase-specific phenomenon that requires the formation of O(6)
      MeG:T mismatches. Chk1 associates with p50 following S(N)1-methylation, and
      phosphorylation of p50 by Chk1 results in the inhibition of NF-kappaB DNA
      binding. Expression of an unphosphorylatable p50 mutant blocks inhibition of NF
      kappaB-regulated antiapoptotic gene expression and attenuates S(N)1-methylator
      induced cytotoxicity. While O(6)-MeG:T-induced, p50-dependent signaling is not
      sufficient to induce cell death, this pathway sensitizes cells to the cytotoxic
      effects of DNA breaks.

PMID- 22152482
TI  - DNA damage-induced RORalpha is crucial for p53 stabilization and increased
      apoptosis.
AB  - A critical component of the DNA damage response is the p53 tumor suppressor, and
      aberrant p53 function leads to uncontrolled cell proliferation and malignancy.
      Several molecules have been shown to regulate p53 stability; however, genome-wide
      systemic approaches for determining the affected, specific downstream target
      genes have not been extensively studied. Here, we first identified an orphan
      nuclear receptor, RORalpha, as a direct target gene of p53, which contains
      functional p53 response elements. The functional consequences of DNA damage
      induced RORalpha are to stabilize p53 and activate p53 transcription in a
      HAUSP/Usp7-dependent manner. Interestingly, microarray analysis revealed that
      RORalpha-mediated p53 stabilization leads to the activation of a subset of p53
      target genes that are specifically involved in apoptosis. We further confirmed
      that RORalpha enhances p53-dependent, in vivo apoptotic function in the
      Drosophila model system. Together, we determined that RORalpha is a p53 regulator
      that exerts its role in increased apoptosis via p53.

PMID- 22152484
TI  - Live cell imaging of telomerase RNA dynamics reveals cell cycle-dependent
      clustering of telomerase at elongating telomeres.
AB  - The telomerase, which is composed of both protein and RNA, maintains genome
      stability by replenishing telomeric repeats at the ends of chromosomes. Here, we
      use live-cell imaging to follow yeast telomerase RNA dynamics and recruitment to
      telomeres in single cells. Tracking of single telomerase particles revealed a
      diffusive behavior and transient association with telomeres in G1 and G2 phases
      of the cell cycle. Interestingly, concurrent with telomere elongation in late S
      phase, a subset of telomerase enzyme clusters and stably associates with few
      telomeres. Our data show that this clustering represents elongating telomerase
      and it depends on regulators of telomerase at telomeres (MRX, Tel1, Rif1/2, and
      Cdc13). Furthermore, the assay revealed premature telomere elongation in G1 in a
      rif1/2 strains, suggesting that Rif1/2 act as cell-cycle dependent negative
      regulators of telomerase. We propose that telomere elongation is organized around
      a local and transient accumulation of several telomerases on a few telomeres.

PMID- 22152483
TI  - Dual function of Sdh3 in the respiratory chain and TIM22 protein translocase of
      the mitochondrial inner membrane.
AB  - The mitochondrial inner membrane harbors the complexes of the respiratory chain
      and translocase complexes for precursor proteins. We have identified a further
      subunit of the carrier translocase (TIM22 complex) that surprisingly is identical
      to subunit 3 of respiratory complex II, succinate dehydrogenase (Sdh3). The
      membrane-integral protein Sdh3 plays specific functions in electron transfer in
      complex II. We show by genetic and biochemical approaches that Sdh3 also plays
      specific functions in the TIM22 complex. Sdh3 forms a subcomplex with Tim18 and
      is involved in biogenesis and assembly of the membrane-integral subunits of the
      TIM22 complex. We conclude that the assembly of Sdh3 with different partner
      proteins, Sdh4 and Tim18, recruits it to two different mitochondrial membrane
      complexes with functions in bioenergetics and protein biogenesis, respectively.

PMID- 22152485
TI  - In vivo and transcriptome-wide identification of RNA binding protein target
      sites.
AB  - Animal mRNAs are regulated by hundreds of RNA binding proteins (RBPs). The
      identification of RBP targets is crucial for understanding their function. A
      recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to
      target RNAs in cells prior to immunoprecipitation. Here, we establish iPAR-CLIP
      (in vivo PAR-CLIP) to determine, at nucleotide resolution, transcriptome-wide
      binding sites of GLD-1, a conserved, germline-specific translational repressor in
      C. elegans. We identified 439 reproducible target mRNAs and demonstrate an
      excellent dynamic range of target detection by iPAR-CLIP. Upon GLD-1 knockdown,
      protein but not mRNA expression of the 439 targets was specifically upregulated,
      demonstrating functionality. Finally, we discovered strongly conserved GLD-1
      binding sites near the start codon of target genes. These sites are functional in
      vitro and likely confer strong repression in vivo. We propose that GLD-1
      interacts with the translation machinery near the start codon, a so-far-unknown
      mode of gene regulation in eukaryotes.

PMID- 22152487
TI  - Vasculopathy, hematological, and immune abnormalities associated with levamisole
      contaminated cocaine use.
AB  - OBJECTIVES: To report 4 cases of cocaine-related purpura and to review previously
      reported cases of levamisole, levamisole-contaminated cocaine, and cocaine
      induced vasculopathy. METHODS: We describe 4 patients suspected of vasculopathy
      associated with levamisole-tainted cocaine use. A retrospective review of the
      literature was performed using the PubMed, PubJet, MD consult, and Cochrane
      review databases. RESULTS: Four cases (2 females and 2 males), 46 to 55 years of
      age, presented with cocaine-related purpura, mainly affecting the ears,
      neutropenia, and autoantibodies. Skin biopsies revealed a mixed pattern of
      leukocytoclastic vasculitis and microvascular thrombosis in 2 cases, and pure
      thrombosis in the third case. The mixed vasculopathic pattern in association with
      neutropenia, both known adverse effects of levamisole, and levamisole positivity
      in 2 cases point to this compound as the true etiologic agent in our patients.
      Eleven cases of levamisole-contaminated cocaine-induced vasculopathy have been
      described in the English literature. Among these, 10 were females. Age range was
      22 to 57 years. Urine levamisole positivity was tested and confirmed in 3 of the
      11 cases. The clinical characteristics, laboratory features, histology,
      treatment, and recovery rates were compared for the published cases of
      levamisole, levamisole-contaminated cocaine, and cocaine-induced vasculopathy.
      CONCLUSIONS: Adulterated cocaine abuse is an increasingly recognized phenomenon
      in North America. Levamisole is among the many contaminants that have been
      detected in seized cocaine throughout North America and Europe. Recent reports
      described an association between levamisole-tainted cocaine and purpuric skin
      rash, neutropenia, and the presence of autoantibodies.

PMID- 22152486
TI  - Malacological survey and geographical distribution of vector snails for
      schistosomiasis within informal settlements of Kisumu City, western Kenya.
AB  - BACKGROUND: Although schistosomiasis is generally considered a rural phenomenon,
      infections have been reported within urban settings. Based on observations of
      high prevalence of Schistosoma mansoni infection in schools within the informal
      settlements of Kisumu City, a follow-up malacological survey incorporating 81
      sites within 6 informal settlements of the City was conducted to determine the
      presence of intermediate host snails and ascertain whether active transmission
      was occurring within these areas. METHODS: Surveyed sites were mapped using a
      geographical information system. Cercaria shedding was determined from snails and
      species of snails identified based on shell morphology. Vegetation cover and
      presence of algal mass at the sites was recorded, and the physico-chemical
      characteristics of the water including pH and temperature were determined using a
      pH meter with a glass electrode and a temperature probe. RESULTS: Out of 1,059
      snails collected, 407 (38.4%) were putatively identified as Biomphalaria
      sudanica, 425 (40.1%) as Biomphalaria pfeifferi and 227 (21.5%) as Bulinus
      globosus. The spatial distribution of snails was clustered, with few sites
      accounting for most of the snails. The highest snail abundance was recorded in
      Nyamasaria (543 snails) followed by Nyalenda B (313 snails). As expected, the
      mean snail abundance was higher along the lakeshore (18 +/- 12 snails) compared
      to inland sites (dams, rivers and springs) (11 +/- 32 snails) (F(1, 79) = 38.8, P
      < 0.0001). Overall, 19 (1.8%) of the snails collected shed schistosome cercariae.
      Interestingly, the proportion of infected Biomphalaria snails was higher in the
      inland (2.7%) compared to the lakeshore sites (0.3%) (P = 0.0109). B. sudanica
      was more abundant in sites along the lakeshore whereas B. pfeifferi and B.
      globosus were more abundant in the inland sites. Biomphalaria and Bulinus snails
      were found at 16 and 11 out of the 56 inland sites, respectively. CONCLUSIONS:
      The high abundance of Biomphalaria and Bulinus spp. as well as observation of
      field-caught snails shedding cercariae confirmed that besides Lake Victoria, the
      local risk for schistosomiasis transmission exists within the informal
      settlements of Kisumu City. Prospective control interventions in these areas need
      to incorporate focal snail control to complement chemotherapy in reducing
      transmission.

PMID- 22152488
TI  - Spontaneous pneumothorax in Wegener's granulomatosis: case report and literature
      review.
AB  - BACKGROUND: Pulmonary manifestations of Wegener's granulomatosis (WG) are present
      in 45% of cases at the onset of the disease, and they reach 85% of the patients
      during its evolution. Pulmonary affection usually starts with unspecific symptoms
      such as cough, dyspnea, hemoptysis, and pleuritis. Pulmonary nodules are 1 of the
      most common manifestations. The prevalence of pleural affection is 10 to 20%.
      However, spontaneous pneumothorax is extremely rare. Although its real incidence
      is unknown, according to different classic series, it ranges between 3 and 5% of
      the cases. OBJECTIVE: To present a new case of spontaneous pneumothorax in a
      patient suffering WG and a brief review on this subject. METHODS: We report our
      experience in a case of spontaneous pneumothorax due to WG. We also review the
      literature through a PubMed search between 1960 and 2010, using a broad range of
      keywords related to WG and spontaneous pneumothorax. Publications were evaluated
      for the demographic features of patients, manifestations of the disease, and
      outcome. RESULTS: Despite the large prevalence of the respiratory involvement,
      spontaneous pneumothorax is extremely rare, with only 21 cases reported in the
      literature. CONCLUSION: Pneumothorax is a rare complication in WG cases, without
      a clear pathogenic mechanism involved.

PMID- 22152489
TI  - Demyelinating disease in patients treated with TNF antagonists in rheumatology:
      data from BIOBADASER, a pharmacovigilance database, and a systematic review.
AB  - OBJECTIVES: To estimate the rate of demyelinating diseases in patients with
      rheumatic diseases treated with tumor necrosis factor (TNF) antagonists and to
      describe the cases reported to 3 different pharmacovigilance sources. METHODS:
      All confirmed cases of demyelinating disease, optic neuritis, and multiple
      sclerosis (MS) in patients with rheumatic diseases treated with TNF-antagonists
      were reviewed from 3 different sources: (1) the Spanish Registry of biological
      therapies in rheumatic diseases (BIOBADASER); (2) the Spanish Pharmacovigilance
      Database of Adverse Drug Reactions (FEDRA); and (3) a systematic review (PubMed,
      EMBASE, and the Cochrane Library). In BIOBADASER, the incidence rate per 1000
      patients was estimated with a 95% confidence interval (95% CI). RESULTS: In
      21,425 patient-years in BIOBADASER, there were 9 patients with confirmed
      demyelinating disease, 4 with optic neuritis, and 1 with MS. In addition, 22
      patients presented polyneuropathies, paresthesias, dysesthesias, facial palsy, or
      vocal cord paralysis without confirmed demyelination. The incidence rate of
      demyelinating disease in patients with rheumatic diseases exposed to TNF
      antagonists in BIOBADASER was 0.65 per 1000 patient-years (95% CI: 0.39-1.1). The
      incidence of MS in BIOBADASER was 0.05 (95% CI: 0.01-0.33), while the incidence
      in the general Spanish population was 0.02 to 0.04 cases per 1000. Compared with
      BIOBADASER, cases in FEDRA (n = 19) and in the literature (n = 48) tend to be
      younger, have shorter exposure to TNF-antagonists, and recover after
      discontinuation of the drug. CONCLUSIONS: It is not clear whether TNF antagonists
      increase the incidence of demyelinating diseases in patients with rheumatic
      diseases. Differences between cases depending on the pharmacovigilance source
      could be explained by selective reporting bias outside registries.

PMID- 22152490
TI  - Fast IMRT by increasing the beam number and reducing the number of segments.
AB  - PURPOSE: The purpose of this work is to develop fast deliverable step and shoot
      IMRT technique. A reduction in the number of segments should theoretically be
      possible, whilst simultaneously maintaining plan quality, provided that the
      reduction is accompanied by an increased number of gantry angles. A benefit of
      this method is that the segment shaping could be performed during gantry motion,
      thereby reducing the delivery time. The aim was to find classes of such solutions
      whose plan quality can compete with conventional IMRT. MATERIALS/METHODS: A
      planning study was performed. Step and shoot IMRT plans were created using direct
      machine parameter optimization (DMPO) as a reference. DMPO plans were compared to
      an IMRT variant having only one segment per angle ("2-Step Fast"). 2-Step Fast is
      based on a geometrical analysis of the topology of the planning target volume
      (PTV) and the organs at risk (OAR). A prostate/rectum case, spine
      metastasis/spinal cord, breast/lung and an artificial PTV/OAR combination of the
      ESTRO-Quasimodo phantom were used for the study. The composite objective value
      (COV), a quality score, and plan delivery time were compared. The delivery time
      for the DMPO reference plan and the 2-Step Fast IMRT technique was measured and
      calculated for two different linacs, a twelve year old Siemens PrimusTM ("old"
      linac) and two Elekta SynergyTM "S" linacs ("new" linacs). RESULTS: 2-Step Fast
      had comparable or better quality than the reference DMPO plan. The number of
      segments was smaller than for the reference plan, the number of gantry angles was
      between 23 and 34. For the modern linac the delivery time was always smaller than
      that for the reference plan. The calculated (measured) values showed a mean
      delivery time reduction of 21% (21%) for the new linac, and of 7% (3%) for the
      old linac compared to the respective DMPO reference plans. For the old linac, the
      data handling time per beam was the limiting factor for the treatment time
      reduction. CONCLUSIONS: 2-Step Fast plans are suited to reduce the delivery time,
      especially if the data handling time per beam is short. The plan quality can be
      retained or even increased for fewer segments provided more gantry angles are
      used.

PMID- 22152491
TI  - Qualification of an automated device to objectively assess the effect of hair
      care products on hair shine.
AB  - The authors developed and qualified an automated routine screening tool to
      quantify hair shine. This tool is able to separately record individual properties
      of hair shine such as specular reflection and multiple reflection, as well as
      additional features such as sparkle, parallelism of hair fibers, and hair color,
      which strongly affect the subjective ranking by individual readers. A side-by
      side comparison of different hair care and styling products with regard to hair
      shine using the automated screening tool in parallel with standard panel
      assessment showed that the automated system provides an almost identical ranking
      and the same statistical significances as the panel assessment. Provided
      stringent stratification of hair fibers for color and parallelism, the automated
      tool competes favorably with panel assessments of hair shine. In this case, data
      generated with the opsira Shine-Box are clearly superior over data generated by
      panel assessment in terms of reliability and repeatability, workload and time
      consumption, and sensitivity and specificity to detect differences after shampoo,
      conditioner, and leave-in treatment. The automated tool is therefore well suited
      to replace standard panel assessments in claim support, at least as a screening
      tool. A further advantage of the automated system over panel assessments is the
      fact that absolute numeric values are generated for a given hair care product,
      whereas panel assessments can only give rankings of a series of hair care
      products included in the same study. Thus, the absolute numeric data generated
      with the automated system allow comparison of hair care products between studies
      or at different time points after treatment.

PMID- 22152492
TI  - Diguanoside tetraphosphate (Gp4G) is an epithelial cell and hair growth
      regulator.
AB  - Our goal was to study the effect of Gp4G on skin tissues and unravel its
      intracellular action mechanisms. The effects of Gp4G formulation, a liposomic
      solution of Artemia salina extract, on several epidermal, depmal, and hair
      follicle structures were quantified. A 50% increase in hair length and a 30%
      increase in the number of papilla cells were explained by the changes in the
      telogen/anagen hair follicle phases. Increasing skin blood vessels and fibroblast
      activation modified collagen arrangement in dermal tissues. Imunohistochemical
      staining revealed expressive increases of versican (VER) deposition in the
      treated animals (68%). Hela and fibroblast cells were used as in vitro models.
      Gp4G enters both cell lines, with a hyperbolic saturation profile inducing an
      increase in the viabilities of Hela and fibroblast cells. Intracellular ATP and
      other nucleotides were quantified in Hela cells showing a 38% increase in
      intracellular ATP concentration and increases in the intracellular concentration
      of tri- , di- , and monophosphate nucleosides, changing the usual quasi
      equilibrium state of nucleotide concentrations. We propose that this change in
      nucleotide equilibrium affects several biochemical pathways and explains the cell
      and tissue activations observed experimentally.

PMID- 22152493
TI  - Chemical stability and degradation mechanisms of ferulic acid (F.A) within
      various cosmetic formulations.
AB  - Ferulic acid (F.A) receives significant interest in the beauty industry with
      regard to its skin-whitening and anti-oxidant properties. However, its use in
      cosmetics is limited due to pH- and temperature-related instabilities. In this
      study, we investigated the stability of F.A in eight different prototype
      formulae. The results confirmed that in our conditions the stability of F.A is pH
      and temperature-related. Additionally, the nature of the solvent dipropylene
      glycol (DPPG) showed a capacity to stabilize F.A. A series of experiments was
      further planned for studying the mechanism of degradation of F.A. In a prototype
      of a cosmetic medium, F.A degrades first through a decarboxylation step, leading
      to 4-hydroxy-3-methoxystyrene (PVG). Further, F.A and PVG are both involved in an
      additional reaction, resulting in the trans-conjugation dimer of PVG. The
      consequences of these results in formulating F.A are discussed.

PMID- 22152494
TI  - Clinical efficacy of facial masks containing yoghurt and Opuntia humifusa Raf. (F
      YOP).
AB  - Facial packs or masks are popular beauty treatments that are thought to improve
      skin quality. We formulated a yoghurt pack using natural ingredients (F-YOP),
      with consideration of skin affinity, safety, health, and beauty. Then, we
      performed an in vitro assessment of biological activity and in vivo assessments
      of moisture, TEWL, melanin content, and elasticity. Facial areas treated with F
      YOP showed increased moisture compared to control regions: 89+/-6.26% (forehead),
      140.72+/-10.19% (cheek), and 123.29+/-6.67% (chin). Transepidermal water loss
      (TEWL) values were decreased in the treated areas compared to control: 101.38+/
      6.95% (forehead), 50.37+/-5.93% (cheek), and l57.81+/-10.88% (chin). Elasticity
      was decreased in the control region, whereas the treatment region did not change.
      The initial elasticity was maintained in the cheek. F-YOP exhibited activity on
      DPPH radical scavenging, SOD-like activity, and lipoxygenase activity. F-YOP
      treatment successfully improved the moisture, brightness, and elasticity of
      treated skin.

PMID- 22152495
TI  - Use of non-melanocytic HEK293 cells stably expressing human tyrosinase for the
      screening of anti-melanogenic agents.
AB  - Tyrosinase (TYR) from mushrooms has been inappropriately used in the screening
      assay for hypopigmenting agents even though its biochemical properties are
      different from those of human TYR. Cell-free extracts of human epidermal
      melanocyes (HEMs) could be another choice for the assay, but HEMs grow too slowly
      to get a sufficient amount of cell-free extracts. In the present study, human
      embryonic kidney (HEK) 293 cells were transfected with a human TYR construct to
      establish a cell line that grows rapidly and expresses human TYR constitutively.
      Cell-free extracts of the established cell line, HEK293-TYR, were tentatively
      used in the screening assays for 11 phenylpropanoids that have chemical
      structures similar to that of L-tyrosine, the substrate of TYR. Of the 11
      compounds, the strongest inhibition of TYR activity was shown by p-coumaric acid
      (IC50, 3 MUM), followed by 3-(4-hydroxyphenyl)propionic acid (50 MUM) and 3-(4
      hydroxyphenyl)lactic acid (70 MUM). The results indicate that p-coumaric acid has
      an optimal chemical structure for the inhibition of TYR. The effects of these
      phenylpropanoids on melanin synthesis in HEMs correlated well with their effects
      on TYR activity in vitro. This study demonstrated that HEK293-TYR cells can be a
      good source of the human TYR enzymes needed in the screening assay of anti
      melanogenic agents.

PMID- 22152496
TI  - Prevalence, patterns, and correlates of co-occurring substance use and mental
      disorders in the United States: variations by race/ethnicity.
AB  - OBJECTIVE: This study examines racial/ethnic differences in the prevalence,
      patterns, and correlates of co-occurring substance use and mental disorders (COD)
      among Whites, Blacks, Latinos, and Asians using data from the Collaborative
      Psychiatric Epidemiology Studies. METHOD: We first estimated the prevalence of
      various combinations of different co-occurring depressive and anxiety disorders
      among respondents with alcohol, drug, and any substance use (alcohol or drug)
      disorders in each racial/ethnic group. We then estimated the prevalence of
      different patterns of onset and different psychosocial correlates among
      individuals with COD of different racial/ethnic groups. We used weighted linear
      and logistic regression analysis controlling for key demographics to test the
      effect of race/ethnicity. Tests of differences between specific racial/ethnic
      subgroups were only conducted if the overall test of race was significant.
      RESULTS: Rates of COD varied significantly by race/ethnicity. Approximately 8.2%
      of Whites, 5.4% of Blacks, 5.8% of Latinos, and 2.1% of Asians met criteria for
      lifetime COD. Whites were more likely than persons in each of the other groups to
      have lifetime COD. Irrespective of race/ethnicity, most of those with COD
      reported that symptoms of mental disorders occurred before symptoms of substance
      use disorders. Only rates of unemployment and history of psychiatric
      hospitalization among individuals with COD were found to vary significantly by
      racial/ethnic group. CONCLUSIONS: Our findings underscore the need to further
      examine the factors underlying differences between minority and nonminority
      individuals with COD as well as how these differences might affect help seeking
      and utilization of substance abuse and mental health services.

PMID- 22152497
TI  - Social anxiety and self-consciousness in binge eating disorder: associations with
      eating disorder psychopathology.
AB  - OBJECTIVE: Research has consistently shown that anxiety disorders are common
      among individuals with eating disorders. Although social phobia has been found to
      be highly associated with eating disorders, less is known about social anxiety in
      individuals with binge eating disorder (BED). The present study examined
      associations between social anxiety and self-consciousness with body mass index
      (BMI) and eating disorder psychopathology in BED. METHODS: Participants were 113
      overweight or obese treatment-seeking men and women with BED. Participants were
      administered semistructural diagnostic clinical interviews and completed a
      battery of self-report measures. RESULTS: Social anxiety was positively and
      significantly correlated with shape and weight concerns and binge eating
      frequency. After accounting for depressive levels, social anxiety and self
      consciousness accounted for significant variance in eating, shape, and weight
      concerns and overall eating disorder global severity scores (Eating Disorder
      Examination). Social anxiety also accounted for significant variance in binge
      eating frequency after covarying for depressive levels. Social anxiety and self
      consciousness were not significantly associated with BMI or dietary restraint.
      DISCUSSION: Our findings suggest that greater social anxiety and heightened self
      consciousness are associated with greater eating disorder psychopathology, most
      notably with greater shape and weight concerns and binge eating frequency in
      patients with BED. Social anxiety and self-consciousness do not appear to be
      merely functions of excess weight, and future research should examine whether
      they contribute to the maintenance of binge eating and associated eating disorder
      psychopathology.

PMID- 22152498
TI  - Iron requirements based upon iron absorption tests are poorly predicted by
      haematological indices in patients with inactive inflammatory bowel disease.
AB  - Fe deficiency and Fe-deficiency anaemia are common in patients with inflammatory
      bowel disease (IBD). Traditional clinical markers of Fe status can be skewed in
      the presence of inflammation, meaning that a patient's Fe status can be
      misinterpreted. Additionally, Fe absorption is known to be down-regulated in
      patients with active IBD. However, whether this is the case for quiescent or
      mildly active disease has not been formally assessed. The present study aimed to
      investigate the relationship between Fe absorption, Fe requirements and standard
      haematological indices in IBD patients without active disease. A group of twenty
      nine patients with quiescent or mildly active IBD and twenty-eight control
      subjects undertook an Fe absorption test that measured sequential rises in serum
      Fe over 4 h following ingestion of 200 mg ferrous sulphate. At baseline, serum
      Fe, transferrin saturation, non-transferrin-bound Fe (NTBI), ferritin and soluble
      transferrin receptor were all measured. Thereafter (30-240 min), only serum Fe
      and NTBI were measured. Fe absorption did not differ between the two groups (P =
      0.9; repeated-measures ANOVA). In control subjects, baseline haematological
      parameters predicted Fe absorption (i.e. Fe requirements), but this was not the
      case for patients with IBD. Fe absorption is normal in quiescent or mildly active
      IBD patients but standard haematological parameters do not accurately predict Fe
      requirements.

PMID- 22152500
TI  - Child abuse investigation: police officers and secondary traumatic stress.
AB  - Child protection is an area of police work which has expanded in the last decade,
      leading to an increase in the number of police officers working in departments
      which specialise in investigating cases of child abuse. Police officers in this
      field may be at greater risk of experiencing secondary traumatic stress but there
      remains a paucity of research in this area of policing. Analogies can be drawn to
      existing research in policing and with social service workers involved in child
      protection. The paper finishes off with implications for police forces to ensure
      safe working environments and appropriate counselling for employees.

PMID- 22152499
TI  - The existence of species rests on a metastable equilibrium between inbreeding and
      outbreeding. An essay on the close relationship between speciation, inbreeding
      and recessive mutations.
AB  - BACKGROUND: Speciation corresponds to the progressive establishment of
      reproductive barriers between groups of individuals derived from an ancestral
      stock. Since Darwin did not believe that reproductive barriers could be selected
      for, he proposed that most events of speciation would occur through a process of
      separation and divergence, and this point of view is still shared by most
      evolutionary biologists today. RESULTS: I do, however, contend that, if so much
      speciation occurs, the most likely explanation is that there must be conditions
      where reproductive barriers can be directly selected for. In other words,
      situations where it is advantageous for individuals to reproduce preferentially
      within a small group and reduce their breeding with the rest of the ancestral
      population. This leads me to propose a model whereby new species arise not by
      populations splitting into separate branches, but by small inbreeding groups
      "budding" from an ancestral stock. This would be driven by several advantages of
      inbreeding, and mainly by advantageous recessive phenotypes, which could only be
      retained in the context of inbreeding. Reproductive barriers would thus not arise
      as secondary consequences of divergent evolution in populations isolated from one
      another, but under the direct selective pressure of ancestral stocks. Many
      documented cases of speciation in natural populations appear to fit the model
      proposed, with more speciation occurring in populations with high inbreeding
      coefficients, and many recessive characters identified as central to the
      phenomenon of speciation, with these recessive mutations expected to be
      surrounded by patterns of limited genomic diversity. CONCLUSIONS: Whilst adaptive
      evolution would correspond to gains of function that would, most of the time, be
      dominant, this type of speciation by budding would thus be driven by mutations
      resulting in the advantageous loss of certain functions since recessive mutations
      very often correspond to the inactivation of a gene. A very important further
      advantage of inbreeding is that it reduces the accumulation of recessive
      mutations in genomes. A consequence of the model proposed is that the existence
      of species would correspond to a metastable equilibrium between inbreeding and
      outbreeding, with excessive inbreeding promoting speciation, and excessive
      outbreeding resulting in irreversible accumulation of recessive mutations that
      could ultimately only lead to extinction.

PMID- 22152501
TI  - A new approach to measuring work-related well-being.
AB  - The main aim of this study was to develop a short questionnaire to assess work
      related well-being from the organizational behaviour perspective. The short well
      being questionnaire enables measuring longitudinal work-related well-being. Work
      related well-being was assessed with a 147-item questionnaire covering both
      organizational and intrinsic factors of work-related well-being. The
      questionnaire consisted of 27 categories. The respondents were 114 women (65%)
      and 62 men (35%), mean age 39.2 years, in various occupations. From the extensive
      questionnaire a shorter questionnaire with 33 items was developed by principal
      component analysis. The Kaiser-Meyer-Olkin measure to test the sampling adequacy
      of 27 factor solutions varied from .62 to .91 and Cronbach?s alpha was .74-.94.
      Most kappa values of the shorter questionnaire were .50-.94 (p < .001). The
      reliability of the short version was comparable to that of the original
      questionnaire. The short one could also be suitable for Internet and mobile
      questionnaire applications.

PMID- 22152502
TI  - Physical symptoms in young adults and their use of different computers and mobile
      phones.
AB  - This paper presents the use of new technical equipment by young adults (30 years
      old or younger), and the physical symptoms they have. The paper then analyses how
      the symptoms are associated with the use of computers and mobile phones, taking
      into account the background information. The study is based on a survey of 15 000
      working-age (18-65) Finns. The responses (1563) covering young adults' physical
      symptoms were analysed. Altogether 53.3% of all young adults had pretty often or
      more frequently pain, numbness or aches in the neck and 32.2% had aches in the
      hip and lower back. Women experienced more pain, numbness or aches in the neck
      (65.0%) than men (34.5%). The use of different computers at leisure quite often
      had an association with some symptoms in different parts of the body. In
      addition, exhaustion at work had associations with some physical symptoms. In the
      future, it is essential to note ergonomic reasons and exhaustion at work when
      young adults experience pain, numbness or aches.

PMID- 22152503
TI  - The relation between upper limb muscle and brain activity in two precision levels
      of repetitive light tasks.
AB  - A study was conducted to investigate the effects of repetitive light tasks of low
      and high precision on upper limb muscles and brain activities. Surface
      electromyography (EMG) and electroencephalography (EEG) were used to measure the
      muscle and brain activity of 10 subjects. The results show that the root-mean
      square (RMS) and mean power frquency (MPF) of the muscle activity and the mean
      power of the EEG alpha bands were higher on the high-precision task than on the
      low-precision one. There was also a high and significant correlation between
      upper limb muscle and brain activity during the tasks. The longer the time and
      the more precise the task, the more the subjects become fatigued both physically
      and mentally. Thus, these results could be potentially useful in managing
      fatigue, especially fatique related to muscle and mental workload.

PMID- 22152505
TI  - Heart rate variability and motion sickness during forklift simulator driving.
AB  - The goal of the study was to determine the effect of a 1-h hour long forklift
      truck virtual simulator driving on the mechanism of autonomic heart rate (HR)
      regulation in operators. The participants were divided into 2 subgroups: subjects
      with no definite inclination to motion sickness (group A) and subjects with a
      definite inclination to motion sickness (group B). Holter monitoring of
      electrocardiogram (ECG) signal was carried out in all subjects during the virtual
      simulator driving. For 12 consecutive epochs of ECG signal, HR variability
      analysis was conducted in time and frequency domains. In subjects with a definite
      inclination to motion sickness after ~30 min of the driving, changes in parameter
      values were found indicating an increase in sympathetic and parasympathetic
      activity with parasympathetic dominance.

PMID- 22152504
TI  - Workplace violence: a study of Turkish workers.
AB  - This research was conducted to address the experience of workplace violence of
      Turkish workers from different sectors and to investigate the impact of the
      exposed violence on their psychological well-being. Data were collected
      anonymously with printed questionnaires from the volunteer participants and
      depended on self-reporting. The response rate was 79.0% (1708/2161). The
      prevalence of workplace violence was found to be 44.8%. The most common type was
      verbal violence together with mobbing (bullying). Victims of physical violence
      were mostly males, whereas females were found to be victims of verbal,
      psychological and sexual violence. Most cases did not result in legal action and
      the victims remained silent. Psychological well-being of exposed workers in terms
      of depression, anxiety and stress seemed to deteriorate. Workplace violence
      remains a silent epidemic in Turkey. Preventive measures against workplace
      violence and social support for violated workers do not exist.

PMID- 22152506
TI  - Impact resistance of guards on grinding machines.
AB  - Guards on machine tools are meant to protect persons from injuries caused by
      parts ejected with high kinetic energy from the machine's working zone. With
      respect to stationary grinding machines, Standard No. EN 13218:2002, therefore,
      specifies minimum wall thicknesses for guards. These values are mainly based on
      estimations and experience instead of systematic experimental investigations.
      This paper shows to what extent simple impact tests with standardizable
      projectiles can be used as basis for the evaluation of the impact resistance of
      guards, provided that not only the kinetic energy of the projectiles used but
      also, among others, their geometry corresponds to the abrasive product fragments
      to be expected.

PMID- 22152507
TI  - Analysis of postural load during tasks related to milking cows-a case study.
AB  - The aim of this study was to analyse postural load during tasks related to
      milking cows of 2 farmers on 2 different farms (one with a manual milk transport
      system, the other with a fully automated milk transport system) as a case study.
      The participants were full-time farmers, they were both healthy and experienced
      in their job. The Ovako Working Posture Analyzing System (OWAS) was used to
      evaluate postural load and postural risk. Postural load was medium for the farmer
      on the farm with a manual milk transport system and high for the farmer working
      on the farm with a fully automated milk transport system. Thus, it can be
      concluded that a higher level of farm mechanization not always mean that the
      farmer's  postural load is lower, but limitation of OWAS should be considered.

PMID- 22152508
TI  - Factors that influence the use of safe patient transfer technique in home care
      service.
AB  - The aim of this pilot study was to explore whether home care service personnel
      used knowledge and skills in transfer technique in their daily work; knowledge
      and skills gained by participating in training programmes, and to identify
      factors that may hinder and support their use. Focus group interviews were held
      with 2 home care service groups in 2 Swedish towns. Individual interviews were
      conducted with the personnel's managers, unit leaders and safety representatives.
      Qualitative content analysis was used. The findings revealed that the personnel
      tried to use their knowledge and skills. However, there were both hindering and
      supporting factors for the use of safe work technique. The findings indicate that
      training programmes in transfer technique should not be implemented as isolated
      actions without considering the physical environment, the wishes of persons
      receiving care and their relatives, the work organisation, the safety culture and
      the role of managers.

PMID- 22152509
TI  - Occupational safety of farmers in the vegetable industry.
AB  - This study aimed to determine unsafe farming practices, nonergonomically designed
      equipment, and possible adverse health effects of pesticide exposure. Data were
      gathered with a structured survey, physical examination and blood extraction.
      Environmental monitoring was done for vegetables to determine multipesticide
      residue. Forty-eight percent of respondents reported feeling sick because of
      work. Vegetable residue was found in 16.67% of the samples. Vegetable profenofos
      of appoximately1 mg exceeded the necessary average daily intake of a maximum of
      0.006 mg. Data also showed nonergonomically designed tools and unsafe work
      practices that increased pesticide exposure such as re-entering recently sprayed
      areas, a damaged backpack sprayer, spills during spraying, and no ventilation in
      greenhouses.

PMID- 22152510
TI  - Sharps injury prevention for hospital workers.
AB  - Objectives. The purpose of this study was to collect data on self-reported sharps
      injuries to develop best practices to reduce them. Methods. Data on sharps
      injuries were collected for the period of January-October 2008 using Adverse
      Event Notification Forms already in use at Sema Hospital. Results. On average,
      0.2% of all self-reported injuries were sharps injuries averaging one injury per
      month. Housekeeping staff sustained 64% of such injuries, nurses sustained 36% (5
      incidents). Outpatient clinics experienced the most injuries at 28%, followed by
      the Internal Diseases Inpatient Unit with 21% and the Medical Waste Room with
      14%. Injuries often occurred during contact with medical waste bags (28%) and
      while replacing full sharp-boxes (14%). Conclusion. In summary, reducing needle
      stick injuries is an important component of the occupational and patient safety
      program at Sema Hospital. The research described in this study allowed the
      hospital to provide targeted interventions to increase awareness of the risks of
      needle stick injuries and reduce such injuries. The steps used in the study can
      be used in any health care organization in the world to design a customized
      improvement plan to reduce risk and injury.

PMID- 22152511
TI  - Platelets and endothelium: two key players in percutaneous coronary intervention.

PMID- 22152512
TI  - One-year clinical outcomes in patients with chronic renal failure treated by
      percutaneous coronary intervention with drug-eluting stent.
AB  - BACKGROUND: It is unknown whether the efficacy and safety of drug-eluting stents
      (DES) apply in patients with chronic renal failure (CRF). AIMS: To compare DES
      with bare metal stents (BMS) for percutaneous coronary intervention (PCI) in CRF
      patients. PATIENTS AND METHODS: Consecutive patients treated by PCI were
      allocated to four groups according to type of stent used (DES versus BMS) and
      creatinine clearance (CrCl). CRF was defined as CrCl less than 60 mL/minute.
      Cardiovascular death, major adverse cardiac events (MACE, defined as
      cardiovascular death, myocardial infarction, stroke and target lesion
      revascularization [TLR]), TLR and definite stent thrombosis (ST) were recorded at
      1 year. RESULTS: We note that 1376 consecutive patients underwent PCI with stent
      within 18 months: 534 (39%) and 492 (36%) patients without CRF and 224 (16%) and
      126 (9%) patients with CRF were treated with BMS and DES, respectively. In the
      entire cohort, patients treated with DES had a higher restenosis risk profile.
      BMS were predominantly (87%) used for ST-segment elevation myocardial infarction.
      At 1 year, 6.2% had cardiovascular death, 15.8% MACE, 7.3% TLR and 1.5% ST.
      Cardiovascular death and MACE occurred less frequently in DES groups. The TLR
      rate was not significantly different in the CRF groups (BMS 9.8% vs DES 7.1%;
      P=0.44). No excess of ST was observed in the DES groups and use of DES was
      independently associated with absence of MACE and TLR. CONCLUSIONS: In patients
      with CRF, DES appear to be at least as effective as BMS--despite a higher
      restenosis risk profile--with no excess of ST at 1 year.

PMID- 22152513
TI  - Left atrial size is an independent predictor of overall survival in patients with
      primary systemic amyloidosis.
AB  - BACKGROUND: Primary systemic amyloidosis is a severe plasma cell disorder
      characterized by the extracellular deposition of amyloid fibrils in different
      organs. Echocardiography is usually performed to assess cardiac involvement. We
      hypothesized that in patients with systemic amyloidosis, simple echocardiographic
      measurement of the left atrial (LA) diameter indexed to the body surface area
      might provide an important risk marker for this disease. METHODS: Between 1997
      and 2011, 134 patients were diagnosed with primary systemic amyloidosis and had
      echocardiography within 28 days; we collected their baseline characteristics and
      biological and echocardiographic data retrospectively. LA enlargement was defined
      as recommended as M-mode LA diameter greater or equal to 23 mm/m(2). RESULTS: One
      hundred and eleven patients (83%) had echocardiographic LA dimension data
      available (mean age 63+/-11 years; 61% men; 31% previously diagnosed with
      systemic hypertension). Mean left ventricular ejection fraction (LVEF) and
      interventricular septum thickness (IVST) were 62+/-12% and 14+/-4 mm,
      respectively. Mean follow-up was 2.8+/-2.9 years (maximum 12 years). Patients
      with LA enlargement had a slightly lower LVEF (P=0.08) and a significantly
      greater IVST (P<0.0001). Overall, 5-year survival was 57+/-5%. However, 1-year
      and 5-year survival rates were markedly reduced in patients with LA enlargement
      versus those without LA enlargement (61+/-7% and 39+/-8% vs 83+/-5% and 72+/-7%,
      respectively; P=0.0007). On multivariable analysis, after adjusting for age, sex,
      LVEF, IVST, presence of hypertension and creatinine concentration, LA enlargement
      remained an independent predictor of overall mortality at 5 years (hazard ratio
      2.47; 95% confidence interval 1.11-5.90; P=0.02). CONCLUSION: LA enlargement, a
      surrogate marker of diastolic dysfunction, is an independent predictor of long
      term mortality and may therefore help to enhance risk stratification and
      management of patients presenting with amyloidosis.

PMID- 22152514
TI  - Undiagnosed airflow limitation in patients at cardiovascular risk.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and cardiovascular
      diseases (CVD) share risk factors and impair each other's prognosis. AIMS: To
      assess the prevalence of airflow limitation (AL) compatible with COPD in a
      population at cardiovascular risk and to identify determinants of AL. METHODS:
      All consecutive patients referred to the cardiovascular prevention unit of a
      university hospital in 2009 were studied in a cross-sectional analysis. Patients
      answered questionnaires on socioeconomic status, medical history and lifestyle,
      and underwent extensive physical examinations, biological measures and spirometry
      testing. AL was defined as FEV1/FVC<0.70, without any history of asthma.
      Determinants of AL were assessed using logistic regression. RESULTS: The sample
      comprised 493 participants (mean age 57.4+/-11.1 years); 60% were men, 18% were
      current smokers, 42% were ex-smokers and 10% of patients had a history of CVD.
      Ten-year risk of coronary heart disease (CHD) according to the Framingham
      equation was intermediate (10-20%) for 25% of patients and high (>20%) for 10%.
      Prevalence of AL was 5.9% (95% confidence interval [CI] 4.0-8.3%) in the whole
      population and 4.3% (2.6-6.6%) among subjects in primary cardiovascular
      prevention. AL was independently associated with CVD (adjusted odds ratio 4.18,
      95% CI 1.72-10.15; P=0.002) but not with Framingham CHD risk. More than 80% of
      patients screened with AL had not been diagnosed previously and more than one in
      two patients was asymptomatic. CONCLUSION: Patients with CVD are at increased
      risk of AL and thus should benefit from AL screening as they are frequently
      asymptomatic.

PMID- 22152515
TI  - Intravascular stenting for the treatment of coarctation of the aorta in
      adolescent and adult patients.
AB  - In the past 10 years, stent implantation has become a real alternative to surgery
      in the management of both native and recurrent coarctation of the aorta in
      adolescents and adults. The purpose of this report is to provide a detailed
      review of stent implantation techniques, including pre-procedure imaging,
      technical aspects and results. The success rate is usually high (around 90%), and
      the procedure results in an increase in the diameter of the coarcted segment, a
      decrease in the transisthmic systolic gradient and a better control of systemic
      hypertension. The most serious complication, rupture of the aorta, can be fatal,
      but is rare (< 2%). Aneurismal dilatation is another potential problem that
      occurs in around 5-9% of cases, and may be related to overstretching and pre
      stent dilatation, so these should be avoided. It is necessary to point out that
      most of these aneurysms are small and conservatively managed. Restenosis is
      another complication that may result from neointimal proliferation, stent recoil
      and stent fracture. Balloon dilatation with a higher inflating pressure or repeat
      stent implantation is proposed herein. A comparison with surgery is also
      discussed, and a follow-up protocol is proposed to capture late complications.
      Owing to good initial and intermediate results, stent implantation is nowadays
      considered as a first-line therapy in most adolescents and adults with
      (re)coarctation of the aorta.

PMID- 22152516
TI  - Shift work and cardiovascular risk factors: new knowledge from the past decade.
AB  - Cardiovascular diseases remain a major public health problem. The involvement of
      several occupational factors has recently been discussed, notably the
      organization of work schedules, e.g. shift work. To analyse the progress of
      knowledge on the relationship between cardiovascular risk factors and shift work.
      A review of English-language literature dealing with the link between
      cardiovascular factors and shift workers (published during 2000-2010) was
      conducted. Studies published in the past 10 years tend to document an impact of
      shift work on blood pressure, lipid profile (triglyceride levels), metabolic
      syndrome and, possibly, body mass index. However, the consequences on glucose
      metabolism are unclear. These results are not yet firmly established, but are
      supported by strong hypotheses. Some advice could reasonably be proposed to guide
      the clinical practitioner.

PMID- 22152517
TI  - Surgery and invasive procedures in patients on long-term treatment with direct
      oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the
      Working Group on Perioperative Haemostasis and the French Study Group on
      Thrombosis and Haemostasis.
AB  - Direct oral anticoagulants (DOAs)--inhibitors of thrombin or factor-Xa--are
      expected to replace vitamin K antagonists in most of their indications. Patients
      receiving long-term treatment with DOAs are likely to be exposed to elective or
      emergency surgery or invasive procedures. Owing to the present lack of experience
      in such conditions, we cannot make recommendations, but only propose
      perioperative management for optimal safety regarding the risk of bleeding and
      thrombosis. DOAs may increase surgical bleeding, they have no validated
      antagonists, they cannot be monitored by simple standardized laboratory assays
      and their pharmacokinetics vary significantly between patients. Although DOAs
      differ in many respects, the proposals in the perioperative setting need not be
      specific to each. For procedures with low haemorrhagic risk, a therapeutic window
      of 48 hours (last administration 24 hours before surgery, restart 24 hours after)
      is proposed. For procedures with medium or high haemorrhagic risk, we suggest
      stopping DOAs 5 days before surgery to ensure complete elimination in all
      patients. Treatment should be resumed only when the risk of bleeding has been
      controlled. In patients at high thrombotic risk (e.g. those in atrial
      fibrillation with a history of stroke), bridging with heparin (low molecular
      weight heparin, or unfractionated heparin, if the former is contraindicated) is
      proposed. In an emergency, the procedure should be postponed for as long as
      possible (minimum 1-2 half-lives) and non-specific antihaemorrhagic agents, such
      as recombinant human activated factor VIIa or prothrombin complex concentrates
      should not be given for prophylactic reversal due to their uncertain benefit
      risk.

PMID- 22152518
TI  - Voluminous coronary fistula between the left coronary artery and the right
      atrium.

PMID- 22152519
TI  - Fibrosis suggested by 3D contrast-enhanced echocardiography in hypertrophic
      cardiomyopathy.

PMID- 22152520
TI  - Potential value of myocardial contrast echocardiography for the detection of
      myocardial fibrosis in hypertrophic cardiomyopathy.

PMID- 22152521
TI  - A foreign body in the heart.

PMID- 22152522
TI  - Hair analysis following chronic smoked-drugs-of-abuse exposure in adults and
      their toddler: a case report.
AB  - INTRODUCTION: Over the past two decades, the study of chronic cocaine and crack
      cocaine exposure in the pediatric population has been focused on the potential
      adverse effects, especially in the prenatal period and early childhood. Non
      invasive biological matrices have become an essential tool for the assessment of
      a long-term history of drug of abuse exposure. CASE REPORT: We analyze the
      significance of different biomarker values in hair after chronic crack exposure
      in a two-year-old Caucasian girl and her parents, who are self-reported crack
      smokers. The level of benzoylecgonine, the principal metabolite of cocaine, was
      determined in segmented hair samples (0 cm to 3 cm from the scalp, and > 3 cm
      from the scalp) following washing to exclude external contamination.
      Benzoylecgonine was detectable in high concentrations in the child's hair, at 1.9
      ng/mg and 7.04 ng/mg, respectively. Benzoylecgonine was also present in the
      maternal and paternal hair samples at 7.88 ng/mg and 6.39 ng/mg, and 13.06 ng/mg
      and 12.97 ng/mg, respectively. CONCLUSION: Based on the data from this case and
      from previously published poisoning cases, as well as on the experience of our
      research group, we conclude that, using similar matrices for the study of chronic
      drug exposure, children present with a higher cocaine concentration in hair and
      they experience more serious deleterious acute effects, probably due to a
      different and slower cocaine metabolism. Consequently, children must be not
      exposed to secondhand crack smoke under any circumstance.

PMID- 22152524
TI  - What is a ventricle?
AB  - On the basis of both developmental and morphological evidence, we would suggest
      that a ventricle is best defined as any chamber within the ventricular mass
      possessing an apical trabecular component. Such ventricles can be of right or
      left morphology, and always coexist. The ventricles are normally formed when
      possessing all three of the inlet, apical trabecular, and outlet components, but
      incomplete when lacking one or both of the inlet and outlet components.
      Ventricles that are incomplete because of lack of the inlet component are always
      hypoplastic, with incomplete right ventricles being positioned antero-superiorly
      within the ventricular mass, and incomplete left ventricles located postero
      inferiorly. Patients having such incomplete ventricles because of the lack of the
      inlet component have functionally univentricular hearts, although the
      functionally univentricular arrangement can also be produced in the setting of
      normally constituted but hypertrophied ventricles. Full analysis of ventricular
      morphology, therefore, requires attention not only to component make-up, but also
      size.

PMID- 22152523
TI  - Screening for methicillin-resistant Staphylococcus aureus (MRSA) in community
      recruited injection drug users: are throat swabs necessary?
AB  - We examined and described colonization of MRSA in the anterior nares and throat
      from 184 community-recruited injection drug users. Thirty-seven (20%) were
      positive for MRSA: most (34, 92%) were carriers in the nares; while only three
      (8%) were carriers detected by throat swabs alone. The majority (29, 78%) of MRSA
      isolates were PVL positive.

PMID- 22152525
TI  - Hypoplastic left heart syndrome and other left heart disease: evolution of
      understanding from population-based analysis to molecular biology and back again-
      a brief overview.
AB  - Congenital cardiac disease is the most common birth defect, occurring in
      approximately 1 in 1000 live births. Congenital cardiac defects have
      associations, whether with gender, race, or specific chromosomal abnormalities,
      potentially allowing grouping of defects to be studied in an effort to develop an
      understanding of aetiological factors. The Baltimore-Washington Infant Study
      provides full ascertainment of a population of infants with congenital cardiac
      disease born in a defined geographic region. The fundamental hypotheses generated
      at the inception of the Baltimore-Washington Infant Study included the central
      idea that the outcome of birth, including the development of congenital cardiac
      malformations, was influenced by environmental factors and their route of
      introduction into a genetically susceptible host. Evidence exists that supports
      the concept that both genetic and environmental factors contribute to the
      development of diseases of the left heart.

PMID- 22152526
TI  - Echocardiography of hypoplastic left heart syndrome.
AB  - Echocardiography is critical in the assessment of patients with hypoplastic left
      heart syndrome. Fundamental techniques and standardised approaches are useful
      when evaluating patients with hypoplastic left heart syndrome prenatally, after
      birth, and before the Norwood operation (Stage 1); after the Norwood operation,
      before and after the superior cavopulmonary anastomosis (Stage 2); before and
      after the Fontan operation (Stage 3); and for chronic surveillance after the
      Fontan operation. From foetal assessment to ongoing surveillance after the Fontan
      procedure, echocardiography remains the primary technique for cardiac monitoring
      in this growing population of children and adults.

PMID- 22152527
TI  - Neonatal surgical reconstruction and peri-operative care for hypoplastic left
      heart syndrome: current strategies.
AB  - The management of newborns with hypoplastic left heart syndrome has changed
      significantly over the past three decades, with an associated dramatic
      improvement in outcomes. The aim of this paper is to discuss current peri
      operative and palliative surgical strategies. Owing to the fact that comparative
      outcomes for these strategies have been addressed in a limited number of
      prospective trials and extractions from multi-centred databases, the primary
      focus of this review is descriptive.

PMID- 22152528
TI  - The hybrid approach--current knowns and unknowns: the perspective of cardiology.
AB  - The hybrid approach to the treatment of patients with hypoplastic left heart
      syndrome most commonly includes transcatheter placement of a stent in the
      arterial duct and surgical placement of bands on the branch pulmonary arteries
      via median sternotomy. This manuscript will review the concept of hybrid
      palliation and discuss topics related to several time intervals: peri-procedural,
      post-procedural, interstage, and comprehensive stage 2.

PMID- 22152529
TI  - Primary care cardiology for patients with hypoplastic left heart syndrome.
AB  - Primary care cardiology is also known as ambulatory cardiology and outpatient
      cardiology. Primary care cardiology for the longitudinal management of patients
      with hypoplastic left heart syndrome is both poorly described and has limited
      evidence to justify its basis. This article briefly discusses the various
      complications that these patients can develop, reviews the medical literature,
      and describes a framework for the care of these complex patients from infancy to
      transition to care by specialists in adults with congenital cardiac disease.

PMID- 22152530
TI  - Feeding, growth, nutrition, and optimal interstage surveillance for infants with
      hypoplastic left heart syndrome.
AB  - Improvement in operative survival of patients with hypoplastic left heart
      syndrome has led to increasing emphasis on prevention of interstage mortality.
      Many centres have improved interstage results through programmes of home
      monitoring following discharge after the Norwood (Stage 1) operation. Experience
      with heightened interstage surveillance has identified failure to thrive during
      infancy as a modifiable risk factor for this population, one that has been linked
      to concerning outcomes at subsequent palliative surgeries. Ensuring normal growth
      as an infant has thus become a priority of management of patients with
      functionally univentricular hearts. Herein, we review the existing evidence for
      best practices in interstage surveillance and optimal nutrition in infants with
      functionally univentricular hearts. In addition, we highlight data presented at
      HeartWeek 2011, from Cardiology 2011, the 15th Annual Update on Pediatric and
      Congenital Cardiovascular Disease, and the 11th Annual International Symposium on
      Congenital Heart Disease.

PMID- 22152531
TI  - Late catheter interventions in hypoplastic left heart syndrome.
AB  - Interventional cardiology plays a key role in the diagnosis and management of
      patients with functionally univentricular physiology after the various stages of
      surgical palliation. The interventions performed are widely variable in type,
      including angioplasty of stenotic vessels and implantation of stents in stenotic
      vessels; closure of defects such as collaterals, leaks in baffles, and
      fenestrations; creation of fenestration; and more. In the setting of venous
      hypertension associated with stenosis at the Fontan baffle, conduit, or pulmonary
      arteries, stent implantation is often preferred, as the aim is to eliminate
      completely the narrowing, given that relatively mild stenosis can have a
      significant detrimental hemodynamic effect in patients with functionally
      univentricular circulation. The procedure is highly successful. In patients who
      fail after Fontan procedure, creation of a fenestration is often performed, with
      variable technique depending on the underlying anatomic substrate. To increase
      chances of patency of the fenestration, implantation of a stent is often
      required, particularly in the setting of an extracardiac conduit. For those
      patients with cyanosis and favorable Fontan hemodynamics, closure of the
      fenestration is performed using atrial septal occluder devices with high success
      rate. Coils compatible with magnetic resonance imaging are used widely to treat
      collateral vessels, although on occasion other specific embolization tools are
      required, such as particles or vascular plugs. Postoperative arch obstruction is
      successfully managed with angioplasty at a younger age, while implantation of a
      stent in the aorta is reserved for older patients. Specifics of these
      interventional procedures as applied to the population of patients with
      functionally univentricular hearts are described in this manuscript.

PMID- 22152532
TI  - New concepts: development of a survivorship programme for patients with a
      functionally univentricular heart.
AB  - Children with functionally univentricular hearts are now surviving into their
      third and fourth decades of life. Although survival alone is a remarkable
      achievement, a lot must still be done to improve the quality and duration of life
      after the Fontan operation. Challenges that may be faced by these patients
      include the impact of the Fontan operation on the liver and the density of bone,
      protein-losing enteropathy, and plastic bronchitis. Paediatric cardiologists are
      familiar with the haemodynamic issues inherent in Fontan physiology; however,
      training in cardiology is often not sufficient to give us a complete
      understanding of the pathophysiology of the complications or of the options for
      treatment. Collaboration with other subspecialists including gastroenterologists,
      endocrinologists, and pulmonologists is essential in order to provide the
      rigorous and nuanced care that our patients need and deserve. A clinic in which a
      patient can see multiple subspecialists, and in which the subspecialists, as a
      group, can discuss each patient, can provide a unique and valuable service for
      patients with a functionally univentricular heart.

PMID- 22152533
TI  - Long-term management of patients with hypoplastic left heart syndrome: the
      diagnostic approach at All Children's Hospital.
AB  - Improved survival in children with hypoplastic left heart syndrome has created a
      sub-population of children and young adults who are living with functionally
      univentricular physiology. Routine surveillance with comprehensive screening for
      structural cardiac disease, functional cardiac disease, arrhythmias,
      thromboembolic disease, and associated dysfunction of end organs is important.
      Future directives will better define the plans of care for routine surveillance
      in patients with hypoplastic left heart syndrome.

PMID- 22152534
TI  - Neurodevelopment and quality of life for children with hypoplastic left heart
      syndrome: current knowns and unknowns.
AB  - The aim of this review is to describe the current state of knowledge related to
      neurodevelopmental outcomes and quality of life for children with hypoplastic
      left heart syndrome and to explore future questions to be answered for this group
      of children.

PMID- 22152535
TI  - Longer-term issues for young adults with hypoplastic left heart syndrome:
      contraception, pregnancy, transition, transfer, counselling, and re-operation.
AB  - Hypoplastic left heart syndrome remained a largely untreated lesion until the
      1980s. In the current era, 75-80% of patients who are managed at "centres of
      excellence" can be expected to survive into young adulthood after staged
      palliation. This improved survival has led to an emerging population of patients
      now entering adulthood with a new set of concerns. We discuss the realised and
      potential issues that will be faced by these patients, including family planning,
      transition, and re-operation.

PMID- 22152536
TI  - Resuscitation and extracorporeal life support during cardiopulmonary
      resuscitation following the Norwood (Stage 1) operation.
AB  - The success of extracorporeal support in providing cardiopulmonary support for a
      variety of patients has led to use of Extracorporeal Life Support, also known as
      ECLS, as a rescue for patients failing conventional resuscitation. The use of
      Extracorporeal Life Support in circumstances of cardiac arrest has come to be
      termed "Extracorporeal Life Support during Cardiopulmonary Resuscitation" or
      "ECPR". Although Extracorporeal Life Support during Cardiopulmonary Resuscitation
      was originally described in patients following repair of congenital cardiac
      defects who suffered a sudden arrest, it has now been used in a variety of
      circumstances for patients both with and without primary cardiac disease.
      Multiple centres have reported successful use of Extracorporeal Life Support
      during Cardiopulmonary Resuscitation in adults and children. However, because of
      the cost, the complexity of the technique, and the resources required,
      Extracorporeal Life Support during Cardiopulmonary Resuscitation is not offered
      in all centres for paediatric patients with refractory cardiac arrest. The
      increasing success and availability of Extracorporeal Life Support during
      Cardiopulmonary Resuscitation in post-operative cardiac patients, coupled with
      the fact that patients undergoing the Norwood (Stage 1) operation can have rapid,
      unpredictable cardiac deterioration and arrest, has led to a steady increase in
      the use of Extracorporeal Life Support during Cardiopulmonary Resuscitation in
      this population. For Extracorporeal Life Support during Cardiopulmonary
      Resuscitation to be most successful, it must be deployed rapidly while the
      patient is undergoing excellent cardiopulmonary resuscitation. Early activation
      of the team that will perform cannulation could possibly shorten the duration of
      cardiopulmonary resuscitation and might improve survival and outcome. More
      research needs to be done to refine the populations and circumstances that offer
      the best outcome with Extracorporeal Life Support during Cardiopulmonary
      Resuscitation, to evaluate the ratios of cost to benefit, and establish the long
      term neurodevelopmental outcomes in survivors.

PMID- 22152537
TI  - Extracorporeal cardiopulmonary resuscitation for post-operative cardiac arrest:
      indications, techniques, controversies, and early results--what is known (and
      unknown).
AB  - Extracorporeal cardiopulmonary resuscitation may be defined as the use of
      extracorporeal membrane oxygenation for the support of patients who do not
      respond to conventional cardiopulmonary resuscitation. Data from national and
      international paediatric databases indicate that the use of extracorporeal
      cardiopulmonary resuscitation is increasing. Guidelines from the American Heart
      Association suggest that any patient with refractory cardiopulmonary
      resuscitation and potentially reversible causes of cardiac arrest is a candidate
      for extracorporeal cardiopulmonary resuscitation. One possible framework for
      selection of patients for extracorporeal cardiopulmonary resuscitation includes
      dividing patients on the basis of favourable or unfavourable characteristics.
      Favourable characteristics include cardiac disease, witnessed event in the
      intensive care unit, ability to deliver effective cardiopulmonary resuscitation,
      active patient monitoring present, favourable arterial blood gases, and early
      institution of extracorporeal membrane oxygenation. Unfavourable characteristics
      potentially include non-cardiac disease, an unwitnessed cardiac arrest,
      ineffective cardiopulmonary resuscitation, and severely acidotic arterial blood
      gases. Considering the significant resources and cost involved in the use of
      extracorporeal cardiopulmonary resuscitation, its use needs to be critically
      examined to improve outcomes, assess neurological recovery and quality of life,
      and help identify populations and other factors that may help guide in the
      selection of patients for successful extracorporeal cardiopulmonary
      resuscitation.

PMID- 22152538
TI  - Intermediate-term outcomes after paediatric cardiac extracorporeal membrane
      oxygenation--what is known (and unknown).
AB  - The use of extracorporeal membrane oxygenation in infants and children with
      cardiac disease who develop refractory cardiogenic shock, cyanosis, or cardiac
      arrest is increasing. Early mortality in children with cardiac disease who
      require extracorporeal membrane oxygenation remains an important issue, as only
      40% of cannulated patients survive to discharge from the hospital. However, it is
      encouraging that 90% children who are discharged alive from the hospital after
      extracorporeal membrane oxygenation are still alive at intermediate-term follow
      up. Surviving patients are at risk for long-term dysfunction of multiple organ
      systems related to their underlying cardiac disease, non-cardiac comorbidities,
      treatment-related complications, and exposure to extracorporeal membrane
      oxygenation. Among the most important acute complications related to support with
      extracorporeal membrane oxygenation is injury to the central nervous system,
      which may contribute to adverse neurodevelopmental outcomes. All of these
      factors, in turn, influence quality of life. Many survivors remain medically
      complex related to their underlying cardiac disease, comorbidities, and sequelae
      of complications acquired over their lifetime. Neurological morbidity clearly
      plays an important role in approximately one-third of survivors, with significant
      deficits in approximately 10%. The limited data about quality of life data that
      are available for survivors of cardiac extracorporeal membrane oxygenation
      suggests that approximately 15-30% of survivors have at least moderately
      decreased quality of life. Overall, published data support the ongoing use of
      support with extracorporeal membrane oxygenation in children with acute cardiac
      failure, most of whom would die without it. However, programmatic efforts to
      improve the selection of patients and the preservation of the function of end
      organs during extracorporeal membrane oxygenation are clearly needed in order to
      improve long-term outcomes.

PMID- 22152539
TI  - Management of children undergoing cardiac transplantation with high Panel
      Reactive Antibodies.
AB  - Highly sensitised children in need of cardiac transplantation have overall poor
      outcomes because of increased risk for dysfunction of the cardiac allograft,
      acute cellular and antibody-mediated rejection, and vasculopathy of the cardiac
      allograft. Cardiopulmonary bypass and the frequent use of blood products in the
      operating room and cardiac intensive care unit, as well as the frequent use of
      homografts, have predisposed potential recipients of transplants to
      allosensitisation. The expansion in the use of ventricular assist devices and
      extracorporeal membrane oxygenation has also contributed to increasing rates of
      allosensitisation in candidates for cardiac transplantation. Antibodies to Human
      Leukocyte Antigen can be detected before transplantation using several different
      techniques, the most common being the "complement-dependent lymphocytotoxicity
      assays". "Solid-phase assays", particularly the "Luminex(r) single antigen bead
      method", offer improved specificity and more detailed information regarding
      specificities of antibodies, leading to improved matching of donors with
      recipients. Allosensitisation prolongs the time on the waiting list for potential
      recipients of transplantation and increases the risk of complications and death
      after transplantation. Aggressive reduction of antibodies to Human Leukocyte
      Antigen in these high-risk patients is therefore of vital importance for long
      term survival of the patient and cardiac allograft. Strategies to decrease Panel
      Reactive Antibody or percent reactive antibody before transplantation include
      plasmapheresis, intravenous administration of immunoglobulin, and specific
      treatment to reduce B-cells, particularly Rituximab. These strategies have
      resulted in varying degrees of success. Antibody-mediated rejection and cardiac
      allograft vasculopathy are two of the most important complications of
      transplantation in patients with high Panel Reactive Antibody. The treatment of
      antibody-mediated rejection in recipients of cardiac transplants is largely
      empirical and includes the use of high-dose corticosteroids, plasmapheresis,
      intravenous administration of immunoglobulins, anti-thymocyte globulin, and
      Rituximab. Cardiac allograft vasculopathy is believed to be secondary to chronic
      complement-mediated endothelial injury and chronic vascular rejection. The use of
      proliferation signal inhibitors, such as sirolimus and everolimus, has been shown
      to delay the progression of cardiac allograft vasculopathy. In some non
      sensitised recipients of cardiac transplants, the de novo formation of antibodies
      to Human Leukocyte Antigen after transplantation may increase the likelihood of
      adverse clinical outcomes. The use of serial testing for donor-specific
      antibodies after cardiac transplantation may be advisable in patients with
      frequent episodes of rejection and patients with history of sensitisation.
      Allosensitisation before transplantation can negatively influence outcomes after
      transplantation. A high incidence of antibody-mediated rejection and graft
      vasculopathy can result in graft failure and decreased survival. Current
      strategies to decrease allosensitisation have helped to expand the pool of
      donors, improve times on the waiting list, and decrease mortality. Centres of
      transplantation offering desensitisation are currently using plasmapheresis to
      remove circulating antibodies; intravenous immunoglobulin to inactivate
      antibodies; cyclophosphamide to suppress B-cell proliferation; and Rituximab to
      deplete B-lymphocytes. Similar approaches are also used to treat antibody
      mediated rejection after transplantation with promising results.

PMID- 22152540
TI  - Informed consent, bioethical equipoise, and hypoplastic left heart syndrome.
AB  - In utero diagnosis of complex progressive cardiac disease such as hypoplastic
      left heart syndrome presents a novel opportunity for antepartum, intrapartum, and
      neonatal management. The clinical possibilities and potential for differing
      outcomes challenge the mother-foetus dyad with regard to informed consent.
      Previous studies reveal that rates of termination of pregnancy for foetuses with
      hypoplastic left heart syndrome vary widely in the United States and Europe,
      leading us to surmise that informed consent may be practised differently. The
      purpose of this paper is to review the ethical considerations and physician
      responsibilities of informed consent as they relate to prenatal and postnatal
      patients with hypoplastic left heart syndrome. Special consideration is paid to
      the informed consent process as practised by the obstetrician, perinatologist,
      paediatric cardiologist, and paediatric cardiac surgeon as it relates to
      termination of pregnancy, comfort care, and surgical palliation. We will argue
      that informed consent as it relates to hypoplastic left heart syndrome is far
      from standardised and that there exists a state of bioethical equipoise
      concerning the extent and limits of its application in the current clinical
      setting.

PMID- 22152541
TI  - Foetal cardiac intervention: an ethical perspective.
AB  - Although recent advances have helped identify cases where foetal cardiac surgery
      might reverse the development of certain lesions, the indications and measurement
      of success in these procedures have yet to be established. Thus, both patients
      and physicians have a "burden of knowledge", whereby a diagnosis is made without
      a clear course of action. The profound issues raised by foetal intervention,
      specifically the question of how concepts such as "patient" and "success" can be
      used, complicate this burden further and test the limits of language and logic.
      Similar issues raised in postmodern philosophy are discussed and can be
      incorporated into foetal cardiac surgery dialogues to produce a multi
      disciplinary approach that will elucidate, not obfuscate, these issues in the
      future.

PMID- 22152542
TI  - Changing attitudes to the management of hypoplastic left heart syndrome: a
      European perspective.
AB  - BACKGROUND AND AIMS: Several years ago, one of us described the difference in
      attitude to patients with hypoplastic left heart syndrome in the United States of
      America and Europe as similar to that between Mars and Venus. Uncertainty remains
      with regard to the long-term prognosis for patients with hypoplastic left heart
      syndrome. This prognosis may be considered in terms of survival, functional
      performance, including exercise capacity and neurodevelopment, as well as
      psychosocial effects on the patient, family, and siblings. Counselling parents
      where either an antenatal or postnatal diagnosis of hypoplastic left heart
      syndrome has been made requires practitioners to give information on these
      prognostic aspects. We wanted to see how attitudes among European surgeons have
      changed over the last few years. METHODS: We performed a review of recent
      European data for hypoplastic left heart syndrome and conducted a survey among
      surgeons in major European centres to ascertain key aspects of their attitudes to
      the management of patients with hypoplastic left heart syndrome and how they
      counsel parents. RESULTS AND CONCLUSIONS: As of January, 2011, 2392 citations in
      the PubMed database were available for the search string "hypoplastic left
      heart". The majority of these were from the centres from the United States of
      America and Europe. The European Association for Cardio-Thoracic Surgery
      Congenital Heart Surgery Database shows an annual increase in the number of
      Norwood (Stage I) operations for hypoplastic left heart syndrome from 2003 to
      2009, with a corresponding reduction in mortality. European rates of antenatal
      detection vary widely between centres, as do the rates of termination for a
      prenatal diagnosis of hypoplastic left heart syndrome. We observed a wide
      variation in the estimates of surgeons for survival and quality of life for
      surgical palliation of hypoplastic left heart syndrome, as well as in their
      estimates for actual rates of termination of pregnancy in their centres. Further,
      there was marked inconsistency in the information given to parents as part of the
      process of counselling. These issues remain to be resolved if parents are to make
      a fully informed decision for their child.

PMID- 22152543
TI  - Joint programmes in paediatric cardiothoracic surgery: a survey and descriptive
      analysis.
AB  - BACKGROUND: Joint programmes, as opposed to regionalisation of paediatric cardiac
      care, may improve outcomes while preserving accessibility. We determined the
      prevalence and nature of joint programmes. METHODS: We sent an online survey to
      125 paediatric cardiac surgeons in the United States in November, 2009 querying
      the past or present existence of a joint programme, its mission, structure,
      function, and perceived success. RESULTS: A total of 65 surgeon responses from 65
      institutions met the criteria for inclusion. Of the 65 institutions, 22 currently
      or previously conducted a joint programme. Compared with primary institutions,
      partner institutions were less often children's hospitals (p = 0.0004), had fewer
      paediatric beds (p = 0.005), and performed fewer cardiac cases (p = 0.03).
      Approximately 47% of partner hospitals performed fewer than 50 cases per year.
      The median distance range between hospitals was 41-60 miles, ranging from 5 to
      1000 miles. Approximately 54% of partner hospitals had no surgeon working
      primarily on-site, and 31% of the programmes conducted joint conferences.
      Approximately 67% of the programmes limited the complexity of cases at the
      partner hospital, and 83% of the programmes had formal contracts between
      hospitals. Of the six programmes whose main mission was to increase referrals to
      the primary hospital, three were felt to have failed. Of the nine programmes
      whose mission was to increase regional quality, eight were felt to be successful.
      CONCLUSION: Joint programmes in paediatric cardiac surgery are common but are
      heterogeneous in structure and function. Programmes whose mission is to improve
      the quality of regional care seem more likely to succeed. Joint programmes may be
      a practical alternative to regionalisation to achieve better outcomes.

PMID- 22152544
TI  - Developing the evidence base for the new guidelines for reduction of
      cardiovascular risk for children by the National Heart, Lung, and Blood
      Institute.
AB  - In 2006, a process was initiated to develop evidence-based paediatric guidelines
      directed towards physicians for reduction of cardiovascular risk. In contrast to
      prior consensus-based guidelines from the National Heart, Lung, and Blood
      Institute, this process was to be evidenced based. This manuscript describes the
      process undertaken to write the evidence-based guidelines from the National
      Heart, Lung, and Blood Institute, beginning with the search for evidence, then
      the process of review of the evidence, and finally the writing of the final
      document. This manuscript also provides some thoughts on how this process might
      be adapted in developing guidelines for caring for patients with congenital
      cardiac disease.

PMID- 22152545
TI  - 12th Annual C. Walton Lillehei Memorial Lecture in Cardiovascular Surgery: Fontan
      conversion--the Chicago experience.
AB  - Between 1994 and 2011, we performed 133 Fontan conversions with arrhythmia
      surgery. Most patients had tricuspid atresia or double-inlet left ventricle with
      prior atriopulmonary connection. Operative mortality was 1.5%, and mean length of
      stay was 14 days. A total of eight patients (6%) have had late cardiac
      transplantation. Freedom from arrhythmia recurrence is 85% at 10 years. For
      properly selected patients with a functionally univentricular heart who have had
      an atriopulmonary Fontan procedure, Fontan conversion with arrhythmia surgery
      significantly improves quality of life.

PMID- 22152546
TI  - Biodegradation and in vitro biocompatibility of polyperoxides: alternating co
      polymers of vinyl monomers and molecular oxygen.
AB  - Vinyl polyperoxides, alternating co-polymers of vinyl monomers and molecular
      oxygen, are a small but important class of polymers with unique properties, such
      as highly exothermic degradation in contrast to common polymers, which generally
      show endothermic degradation. Enzymatic degradation and in vitro biocompatibility
      have been studied for the vinyl polyperoxides polystyrene peroxide (PSP),
      poly(alpha- methylstyrene) peroxide (PAMSP) and poly(methyl methacrylate)
      peroxide (PMMAP). Enzymatic degradation of polyperoxides has been carried out
      using horseradish peroxidase enzyme at room temperature. The rate of the enzyme
      catalyzed degradation depends on enzyme concentrations. The cytotoxicity study
      shows that the polyperoxide has good biocompatibility with no obvious inhibition
      effect on HeLa cell growth up to 120 MUg/ml PSP and PAMSP and up to 60 MUg/ml
      PMMAP. Fluorescence microscopic studies established the cellular viability of
      HeLa cells in the presence of polyperoxides. 

PMID- 22152547
TI  - Comments on "Strategies for regeneration of the bone using porcine adult adipose
      derived mesenchymal stem cells" by E. Monaco, M. Bionaz, et al. Theriogenology
      2011;75:1381-99.

PMID- 22152549
TI  - Complicated Intra-Abdominal Infections Observational European study (CIAO Study).
AB  - Complicated intra-abdominal infections are frequently associated with poor
      prognoses and high morbidity and mortality rates.Despite advances in diagnosis,
      surgery, and antimicrobial therapy, mortality rates associated with complicated
      intra-abdominal infections remain exceedingly high.In order to describe the
      clinical, microbiological, and management-related profiles of both community
      acquired and healthcare-acquired complicated intra-abdominal infections (IAIs),
      the World Society of Emergency Surgery (WSES), in collaboration with the Surgical
      Infections Society of Europe (SIS-E) and other prominent European surgical
      societies, has designed the CIAO study.The CIAO study is a multicenter,
      observational study and will be carried out in various surgical departments
      throughout Europe. The study will include patients undergoing surgery or
      interventional drainage for complicated IAI.

PMID- 22152550
TI  - In the realm of ideas: "inside and outside the box".

PMID- 22152552
TI  - Investigating a candidate cell of origin for diffuse intrinsic pontine glioma.

PMID- 22152551
TI  - The persistence of memory (1931) by Salvador Dali (1904-1989).

PMID- 22152553
TI  - Glioblastoma: the importance of not being ageist.

PMID- 22152554
TI  - DNA-based prediction of scoliosis curve progression.

PMID- 22152555
TI  - What is the real incidence of aneurysmal subarachnoid hemorrhage in the Middle
      East? A preliminary multicenter study in Iran.

PMID- 22152556
TI  - Art, passion, and neurosurgery: the role of the Society of Neurological Surgeons
      in academic neurosurgery.
AB  - Neurosurgery is at a crossroads in a time of economic uncertainty. It is also a
      time of remarkable potential for innovation resulting in dramatic improvement in
      the way neurosurgeons care for patients and the quality of outcomes. Analysis of
      this key time point of neurosurgical history is drawn from reflections for a
      presidential address to the Society of Neurological Surgeons. It is the author's
      opinion that the best of academic neurosurgery must and will accept this
      challenge by developing not only the research but also the creativity and art of
      what neurosurgeons do for maximal patient benefit in research, educational, and
      clinical missions.

PMID- 22152557
TI  - Brain abscess: an antediluvian affliction of the past?

PMID- 22152558
TI  - Brain abscess: aspiration versus excision.

PMID- 22152559
TI  - Deja vu.

PMID- 22152560
TI  - Modern management of aneurysmal subarachnoid hemorrhage.

PMID- 22152561
TI  - Has the introduction of coiling improved therapeutic outcomes for subarachnoid
      hemorrhage? A report from the Japanese PRESAT Group.

PMID- 22152562
TI  - Arteriovenous malformations and associated aneurysms.

PMID- 22152563
TI  - Insurance status and patient outcome after neurosurgery.

PMID- 22152564
TI  - Flow diversion for intracranial aneurysms: optimally defining and evolving a new
      tool and approach.

PMID- 22152565
TI  - Current indications for indocyanine green angiography.

PMID- 22152566
TI  - Trigeminocardiac reflex: a predictable event with unpredictable aspects.

PMID- 22152567
TI  - Meningioma-toward an improved understanding of the role of sex steroids in tumor
      development and progression.

PMID- 22152568
TI  - Hormonal effect on meningioma growth.

PMID- 22152569
TI  - Spinal carcinoid metastasis: rare but important differential diagnosis of a
      spinal mass.

PMID- 22152570
TI  - Contemporary skull fractures: unusual everted fracture.

PMID- 22152571
TI  - Man, mind, and machine: the past and future of virtual reality simulation in
      neurologic surgery.
AB  - OBJECTIVE: To review virtual reality in neurosurgery, including the history of
      simulation and virtual reality and some of the current implementations; to
      examine some of the technical challenges involved; and to propose a potential
      paradigm for the development of virtual reality in neurosurgery going forward.
      METHODS: A search was made on PubMed using key words surgical simulation, virtual
      reality, haptics, collision detection, and volumetric modeling to assess the
      current status of virtual reality in neurosurgery. Based on previous results,
      investigators extrapolated the possible integration of existing efforts and
      potential future directions. RESULTS: Simulation has a rich history in surgical
      training, and there are numerous currently existing applications and systems that
      involve virtual reality. All existing applications are limited to specific task
      oriented functions and typically sacrifice visual realism for real-time
      interactivity or vice versa, owing to numerous technical challenges in rendering
      a virtual space in real time, including graphic and tissue modeling, collision
      detection, and direction of the haptic interface. CONCLUSIONS: With ongoing
      technical advancements in computer hardware and graphic and physical rendering,
      incremental or modular development of a fully immersive, multipurpose virtual
      reality neurosurgical simulator is feasible. The use of virtual reality in
      neurosurgery is predicted to change the nature of neurosurgical education, and to
      play an increased role in surgical rehearsal and the continuing education and
      credentialing of surgical practitioners.

PMID- 22152572
TI  - A review of brain abscess surgical treatment--78 years: aspiration versus
      excision.
AB  - OBJECTIVE: The literature regarding surgical treatment of brain abscess was
      reviewed from 1990 to (and including) 2008 to supplement a previous literature
      review from 1930 to 1990. METHODS: The Ovid Medline database 1950-2009 with the
      year range limited to 1990-2009 was used to identify all articles relating to
      brain abscess. The results were compared with a previously published review from
      1930-1990 by the senior author. RESULTS: The original finding was confirmed that
      the high mortality from aspiration in the pre-computer tomography era decreased
      dramatically after computer tomographic scanning became available. In the present
      review, the mean mortality for aspiration post-1990 was 6.6% for publications
      with more than five patients. With surgical excision by craniotomy, the mean
      mortality in the same period was 12.7%. CONCLUSIONS: The present review suggests
      that aspiration may be the first surgical choice in patients with supratentorial
      parenchymal brain abscesses.

PMID- 22152574
TI  - Vasospasm after aneurysmal subarachnoid hemorrhage: review of randomized
      controlled trials and meta-analyses in the literature.
AB  - OBJECTIVE: Cerebral vasospasm is a major source of morbidity and mortality
      following aneurysmal subarachnoid hemorrhage (SAH). A variety of therapies have
      been utilized to prevent or treat vasospasm. Despite the large number of clinical
      trials, few randomized controlled trials (RCTs) of sufficient quality have been
      published. We review the RCTs and meta-analyses in the literature regarding the
      treatment and prevention of cerebral vasospasm following aneurysmal SAH. METHODS:
      A literature search of MEDLINE, the Cochrane Controlled Trials Registry, and the
      National Institutes of Health/National Library of Medicine clinical trials
      registry was performed in January 2010 using predefined search terms. These
      trials were critically reviewed and categorized based on therapeutic modality.
      RESULTS: Forty-four RCTs and 9 meta-analyses met the search criteria. Significant
      findings from these trials were analyzed. The results of this study were as
      follows: nimodipine demonstrated benefit following aneurysmal SAH; other calcium
      channel blockers, including nicardipine, do not provide unequivocal benefit;
      triple-H therapy, fasudil, transluminal balloon angioplasty, thrombolytics,
      endothelin receptor antagonists, magnesium, statins, and miscellaneous therapies
      such as free radical scavengers and antifibrinolytics require additional study.
      Tirilazad is ineffective. CONCLUSIONS: There are many possible successful
      treatment options for preventing vasospasm, delayed ischemic neurologic deficits,
      and poor neurologic outcome following aneurysmal subarachnoid hemorrhage;
      however, further multicenter RCTs need to be performed to determine if there is a
      significant benefit from their use. Nimodipine is the only treatment that
      provided a significant benefit across multiple studies.

PMID- 22152573
TI  - Determinants of poor outcome after aneurysmal subarachnoid hemorrhage when both
      clipping and coiling are available: Prospective Registry of Subarachnoid
      Aneurysms Treatment (PRESAT) in Japan.
AB  - OBJECTIVE: To examine current determinants of poor outcome after aneurysmal
      subarachnoid hemorrhage (SAH) when ruptured aneurysms are treated with either
      microsurgery (clipping) or endovascular treatment (coiling) depending on each
      patient's characteristics. METHODS: Between March 2006 and February 2007, 534
      patients with SAH were enrolled in the Prospective Registry of Subarachnoid
      Aneurysms Treatment (PRESAT) project. Patients were treated according to the
      preference of investigators who were experienced in performing both clipping and
      coiling. Factors influencing poor outcome (12-month modified Rankin Scale [mRS],
      3-6) were determined using multivariate logistic regression analyses. RESULTS: In
      this cohort, 32.4% of patients were World Federation of Neurosurgical Societies
      (WFNS) grade IV-V, and 28.1% had a poor outcome. Clipping was preferably
      performed for small aneurysms with a wide neck and for middle cerebral artery
      (MCA) aneurysms, whereas coiling was preferred for larger, internal carotid
      artery (ICA) and posterior circulation aneurysms. In addition to increasing age,
      admission WFNS grade IV-V, preadmission aneurysmal rerupture, vasospasm-induced
      cerebral infarct, pneumonia, sepsis, shunt-dependent hydrocephalus and seizure,
      postclipping hemorrhagic complications (odds ratio 4.8, 95% confidence interval
      1.5-15.3, P < 0.01), and postcoiling ischemic complications (odds ratio 4.4, 95%
      confidence interval 1.3-15.2, P < 0.05) significantly caused poor outcomes,
      although the complications did not affect mortality. Type of treatment modality
      and size and location of aneurysms did not influence outcome. CONCLUSIONS:
      Introducing an endovascular treatment option has made aneurysm characteristics
      less important to outcome, but procedural complications are problematic and
      should be reduced to improve outcome.

PMID- 22152575
TI  - Cerebral arteriovenous malformations associated with flow-related and circle of
      Willis aneurysms.
AB  - BACKGROUND: To evaluate the characteristics of brain arteriovenous malformations
      (AVMs) with coexisting flow-related and Willis circle aneurysms. METHODS: The 302
      consecutive retrospectively reviewed patients from the Beijing Tiantan Hospital
      were analyzed in this study. The presence of cerebral aneurysms was confirmed by
      pretreatment selective and superselective angiography. Univariate and
      multivariate analyses were performed for patient age, sex, history of rupture,
      associated aneurysms, AVM size, and deep and superficial venous drainage.
      RESULTS: Of the 302 patients, 41 (13.6%) had AVMs associated with intranidal
      aneurysms, and 33 (10.9%) had AVMs associated with extranidal aneurysms. Of the
      33 patients, 24 (72.7%) had a flow-related and 9 (27.3%) had a Willis circle
      aneurysm. Flow-related and Willis circle aneurysms correlated positively with
      intracranial hemorrhage (P = 0.003), patient age (P = 0.003), and infratentorial
      AVMs (P = 0.040) in multiple univariate analysis. CONCLUSIONS: Flow-related and
      Willis circle aneurysms coexisting with cerebral AVMs frequently are associated
      with initial hemorrhage presentation, patient age, and infratentorial AVM
      location.

PMID- 22152576
TI  - Insurance status and inequalities in outcomes after neurosurgery.
AB  - OBJECTIVE: Little is known about socioeconomic differences in postoperative
      outcomes after neurosurgery. We assessed the relation between insurance status
      and postoperative complication risk, neurosurgical intensive care unit stay, and
      hospital stay after neurosurgery. METHODS: We collected data on 918 consecutive
      craniotomy or spine-related neurosurgical cases in patients at least 18 years of
      age at the University of Michigan Hospitals after April 2006. Bivariate chi(2)
      tests and analysis of variance were used to assess bivariate relations, and
      multivariable logistic regression models and analysis of covariance were used to
      adjust for potential confounders. RESULTS: A total of 11.2% of privately insured
      patients, 23.6% of Medicare patients, 25.8% of Medicaid patients, and 27.3% of
      uninsured patients suffered complications within 30 days of surgery (P < 0.001).
      In adjusted models, odds of postoperative complications among Medicare (odds
      ratio [OR] = 2.1, 95% confidence interval [CI] 1.3-3.3), Medicaid (OR = 3.1, 95%
      CI 1.5-6.1), and uninsured patients (OR = 3.6. 95% CI 1.3-10.3) were higher than
      among privately insured patients. By analysis of covariance, only Medicaid
      patients had significantly longer intensive care unit (P = 0.040) and hospital
      stays (P = 0.028) than privately insured patients. CONCLUSIONS: Our findings
      suggest important socioeconomic disparities in outcomes after neurosurgical
      intervention. Access to postoperative outpatient care may mediate our findings.

PMID- 22152577
TI  - Santiago Ramon y Cajal and Harvey Cushing: two forefathers of neuroscience and
      neurosurgery.
AB  - OBJECTIVE: To summarize the extraordinary accomplishments, and the commonalities,
      between Santiago Ramon y Cajal and Harvey Williams Cushing. METHODS: Existing
      literature describing the lives and achievements of Ramon y Cajal and Cushing, as
      well as personal communication, and the surgical records of the Johns Hopkins
      Hospital, from 1896 to 1912, were reviewed. RESULTS: Both Ramon y Cajal and
      Cushing were men of unusually broad interests and talents, and these shared
      characteristics undoubtedly influenced the career paths and scientific
      investigations they pursued. Although Santiago Ramon y Cajal and Harvey Williams
      Cushing never directly interacted, the links between them can be traced through
      some of their disciples, including Pio del Rio Hortega, Wilder Penfield, and
      Percival Bailey. CONCLUSIONS: Ramon y Cajal and Cushing are widely considered the
      forefathers of neuroscience and neurosurgery, respectively, and their discoveries
      have made lasting impressions on both the scientific and medical communities.

PMID- 22152578
TI  - SILK flow-diverting device for intracranial aneurysms.
AB  - BACKGROUND: The SILK intracranial stent is a Conformite Europeenne mark-approved
      endovascular device. This flow-diversion device is being used in Europe for
      intracranial aneurysm treatment by aneurysm occlusion. The device construct
      creates an intracranial bypass conduit that reconstructs the parent vessel while
      maintaining patency of the perforating arteries and branch arteries. The
      investigators report the first two patients in which the SILK stent was used for
      intracranial aneurysms in the United States. CASE DESCRIPTION: Two patients, one
      with a symptomatic giant posterior communicating artery aneurysm and one with a
      symptomatic fusiform vertebrobasilar junction and basilar artery aneurysm, were
      treated at two separate institutions with the device. A total of three SILK
      stents were placed in these patients. In the first patient, a single device was
      sufficient to cause immediate angiographic stasis within the posterior
      communicating artery aneurysm. However, reversal of anticoagulation and
      antiplatelet therapy was required due to a spontaneous bleed from an intercostal
      artery, and this led to in-stent thrombosis and major stroke. In the second
      patient, the placement of two devices resulted in immediate stasis of the basilar
      artery aneurysm. The patient remained on antiplatelet therapy and was discharged
      without complication. His follow-up angiogram at approximately 2 months showed
      complete occlusion of the aneurysm with parent vessel reconstruction. In both
      patients, immediate stasis was identified, and no immediate neurological
      complications occurred. However, in one patient, a complication occurred that was
      related to reversal of/cessation of antiplatelet therapy. CONCLUSION: In this
      initial U.S. experience with SILK flow-diversion devices, these devices were
      deployed easily and immediate flow stasis in the aneurysm was achieved. Further
      evaluation of this device is needed at multiple centers with adequately trained
      and experienced operators.

PMID- 22152579
TI  - Sudden asystole due to trigeminocardiac reflex during transsphenoidal surgery for
      pituitary tumor.
AB  - BACKGROUND: A sudden attack of an asystolic phenomenon is an extremely rare event
      during transsphenoidal surgery (TSS). It may be caused by an extreme type of
      trigeminocardiac reflex (TCR) during the manipulation of the trigeminal nerve or
      its innervated structures. CASE DESCRIPTION: We report two cases of sudden
      asystole and a case of severe bradycardia due to TCR during TSS. All patients
      were managed successfully by cessation of the surgical manipulation or with the
      injection of an anticholinergic agent. CONCLUSIONS: Although TCR occurs rarely
      and usually is self-limiting, surgeons should be cautious of its occurrence,
      especially when manipulating the cavernous sinus during TSS. This allows the
      early detection and appropriate treatment of this manifestation. Stopping the
      surgical procedure as soon as TCR occurs is likely to normalize the vital
      parameters. In addition, if further manipulations are inevitable, the
      administration of anticholinergic medication should be considered cautiously to
      improve surgical outcomes.

PMID- 22152580
TI  - Intracranial meningiomas in patients with uterine sarcoma treated with long-term
      megestrol acetate therapy.
AB  - OBJECTIVE: To report a series of four patients with uterine sarcoma, including
      one with mullerian adenosarcoma (MA) and three with low-grade endometrial stromal
      sarcoma (LGESS), who developed intracranial meningiomas while receiving the
      progesterone agonist megestrol acetate. METHODS: The hospital records, imaging
      studies, and pathology slides of four patients who were treated for uterine
      sarcomas and subsequently developed intracranial meningiomas were reviewed.
      RESULTS: All patients underwent surgery for their gynecologic cancers and
      received maintenance therapy with long-term hormonal suppression with megestrol
      acetate. Each of the four patients later developed neurologic symptoms secondary
      to intracranial meningiomas. Three patients had more than one meningioma.
      Histopathologic examination of all excised tumors showed strong immunoreactivity
      for progesterone receptors (PRs). CONCLUSIONS: Patients with uterine sarcoma
      subtypes LGESS and MA may be predisposed to develop meningiomas, particularly in
      the setting of long-term treatment with megestrol acetate. Alternatively,
      preexisting, clinically silent meningiomas in these patients may have progressed
      to the point of clinical symptoms in the presence of the progesterone agonist
      megestrol acetate. Without previous imaging studies showing the presence or
      absence of meningioma before initiation of megestrol acetate treatment, there is
      no way to draw definitive conclusions regarding this possibility. Clinical and
      neuroradiologic surveillance for meningiomas should be strongly considered in
      patients with these uterine sarcoma subtypes, particularly in patients undergoing
      long-term suppressive therapy with megestrol acetate.

PMID- 22152581
TI  - Intraoperative Matas test using microscope-integrated intraoperative indocyanine
      green videoangiography with temporary unilateral occlusion of the A1 segment of
      the anterior cerebral artery.
AB  - OBJECTIVE: The aim of the present study was to assess a new technique of surgical
      microscope-based indocyanine green (ICG) videoangiography (VAG) to confirm the
      patency of the anterior communicating artery (AcomA) after clipping AcomA
      aneurysms. METHODS: Aneurysmal clipping of five cases of unruptured, broad-neck
      AcomA aneurysm was performed using the Carl Zeiss Surgical Microscope OPMI
      Pentero INFRARED 800. RESULTS: In all five patients, after clipping AcomA
      aneurysms, the patency of AcomA was confirmed using ICGVAG findings and temporary
      unilateral occlusion of the A1 segment of the anterior cerebral artery using
      temporary clips. Images were excellent and enabled a real-time surgical
      assessment because the structures of interest, including vessels, perforating
      arteries, or residual aneurysm neck, were visible to the surgeon's eye under the
      microscope in all five patients. CONCLUSIONS: ICGVAG and temporary unilateral
      occlusion with clips provides a simple, reliable, real-time, and rapid
      intraoperative assessment of the patency of AcomA. This technique may help to
      improve the quality of neurosurgical procedures.

PMID- 22152582
TI  - Primary intramedullary spinal germ cell tumors.
AB  - BACKGROUND: Intramedullary spinal germ cell tumors are rare lesions, with
      germinomas being the most common variant. METHODS: To date, there have been 23
      reports of primary intramedullary germ cell tumors described in the literature,
      the vast majority occurring in Japanese patients. RESULTS: We present a case of a
      nonmetastatic intramedullary germ cell tumor in a 28-year-old Caucasian woman.
      CONCLUSIONS: Characteristics of intramedullary germ cell tumors are summarized,
      and the current role for surgery and adjuvant radiation and chemotherapy are
      discussed.

PMID- 22152583
TI  - Arachnoiditis ossificans.
AB  - OBJECTIVE: Arachnoiditis ossificans is an uncommon clinical entity in which
      arachnoid ossification leads to clinical symptomatology. In this case report, we
      describe the case of a myelopathic patient with arachnoid ossifications, an
      arachnoid cyst, and syringomyelia coexisting with a herniated thoracic disc at
      the same levels. CASE DESCRIPTION: An 81-year-old woman presented with rapidly
      progressive leg weakness, dysesthetic pains, and urinary incontinence. RESULTS:
      The patient underwent thoracic laminectomy with costotransversectomy for
      resection of ossified arachnoid and re-establishment of cerebrospinal fluid
      pathways. CONCLUSION: Altered cerebrospinal fluid dynamics secondary to the
      obstruction in subarachnoid flow may predispose to the formation of an arachnoid
      cyst, and the cyst itself may be the proximate cause of the myelopathy.

PMID- 22152584
TI  - Spinal carcinoid metastasis with dural invasion.
AB  - OBJECTIVE: To present the unusual finding of a lumbar intradural carcinoid
      metastasis in a 67-year-old man with a primary thymic carcinoid diagnosed 16
      years before presentation. METHODS: The history and imaging findings of this
      patient are presented, and the literature is reviewed. RESULTS: Only three
      patients with intradural carcinoid tumors, including the one described here, have
      been reported. In each case, the tumor was discovered in the lumbar region. All
      patients were treated with surgery. The clinical behavior of metastatic carcinoid
      in the central nervous system (CNS) and the treatment rationale are also
      described. CONCLUSIONS: Carcinoid tumor metastases are rarely identified in the
      CNS even in patients with advanced metastatic disease.

PMID- 22152585
TI  - Everted skull fracture.
AB  - OBJECTIVE: Skull bone fractures are common in trauma. They are usually linear
      undisplaced or depressed; however, a distinct possibility of elevated fracture
      remains. We describe an entity of everted fracture skull in which the fracture
      segment is totally everted. The nature of trauma, management, and complications
      of this unique case are discussed. CASE REPORT: A 21-year-old woman involved in a
      railway accident presented to us with a primary dressing on her wound.
      Investigations revealed an everted fracture skull. She underwent surgery with
      good results. CONCLUSION: We would like to add everted fracture skull to the
      nomenclature describing skull fractures in addition to elevated compound fracture
      skull as a new entity.

PMID- 22152587
TI  - Contraception for individuals with sickle cell disease: a systematic review of
      the literature.
AB  - BACKGROUND: Women with sickle cell disease have an increased risk of pregnancy
      related complications and need safe, effective contraceptive methods to prevent
      unintended pregnancy. STUDY DESIGN: We conducted a systematic review to examine
      the safety of hormonal and intrauterine contraceptive use among women with sickle
      cell disease. RESULTS: Eight articles met the inclusion criteria. The evidence
      was of fair to poor quality and suggested that progestin-only and combined
      hormonal contraception had no effect on frequency of sickle crises or other
      adverse events and no effect on hematologic parameters associated with sickle
      crises. No studies examined the risk of thromboembolism in combined hormonal
      contraceptive users with sickle cell disease. There was insufficient evidence to
      comment on the safety of intrauterine contraception. CONCLUSION: While data are
      limited, there is no evidence to suggest that hormonal contraceptive use among
      women with sickle cell disease is associated with an increased risk of clinical
      complications.

PMID- 22152586
TI  - Identification of urinary metabolites that distinguish membranous lupus nephritis
      from proliferative lupus nephritis and focal segmental glomerulosclerosis.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune
      disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a
      frequent and severe complication of SLE that increases patient morbidity and
      mortality. About 50% of patients with SLE encounter renal abnormalities which, if
      left untreated, can lead to end-stage renal disease. Kidney biopsy is considered
      the criterion standard for diagnosis and staging of LN using the International
      Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was
      developed to help predict renal outcomes and assist with medical decision-making.
      However, kidney biopsy-based classification of LN is highly invasive and
      impractical for real-time monitoring of LN status. Here, nuclear magnetic
      resonance (NMR) spectroscopy-based metabolic profiling was used to identify
      urinary metabolites that discriminated between proliferative and pure membranous
      LN as defined by the ISN/RPS classification, and between LN and primary focal
      segmental glomerulosclerosis (FSGS). METHODS: Metabolic profiling was conducted
      using urine samples of patients with proliferative LN without membranous features
      (Class III/IV; n = 7) or pure membranous LN (Class V; n = 7). Patients with
      primary FSGS and proteinuria (n = 10) served as disease controls. For each
      patient, demographic information and clinical data was obtained and a random
      urine sample collected to measure NMR spectra. Data and sample collection for
      patients with LN occurred around the time of kidney biopsy. Metabolic profiling
      analysis was done by visual inspection and principal component analysis. RESULTS:
      Urinary citrate levels were 8-fold lower in Class V LN compared to Class III/IV
      patients, who had normal levels of urinary citrate (P < 0.05). Class III/IV LN
      patients had > 10-fold lower levels of urinary taurine compared to Class V
      patients, who had mostly normal levels (P < 0.01). Class V LN patients had normal
      urinary hippurate levels compared to FSGS patients, who completely lacked urinary
      hippurate (P < 0.001). CONCLUSIONS: This pilot study indicated differences in
      urinary metabolites between proliferative LN and pure membranous LN patients, and
      between LN and FSGS patients. If confirmed in larger studies, these urine
      metabolites may serve as biomarkers to help discriminate between different
      classes of LN, and between LN and FSGS.

PMID- 22152588
TI  - An overview of four studies of a continuous oral contraceptive (levonorgestrel 90
      mcg/ethinyl estradiol 20 mcg) on premenstrual dysphoric disorder and premenstrual
      syndrome.
AB  - BACKGROUND: This article presents an overview of four studies that evaluated a
      continuous oral contraceptive (OC) containing levonorgestrel (90 mcg) and ethinyl
      estradiol (20 mcg; LNG/EE) for managing premenstrual dysphoric disorder (PMDD)
      and premenstrual syndrome (PMS). STUDY DESIGN: Three randomized, double-blind,
      placebo-controlled trials and one open-label, single-treatment substudy examined
      mean changes from baseline in the Daily Record of Severity of Problems (DRSP) or
      Penn Daily Symptom Rating (DSR). RESULTS: Improvements from baseline in mean DRSP
      and DSR scores were observed, but results were not consistent among the studies.
      Mean percent improvement of premenstrual symptoms ranged from 30% to 59% in
      controlled trials and 56% to 81% in an open-label substudy. A large placebo
      effect was also observed in the placebo-controlled studies. Continuous LNG/EE
      yielded a favorable safety profile. CONCLUSIONS: These data, although not
      consistent, indicate that continuous LNG/EE may reduce the symptoms of PMDD and
      PMS, providing an option for women who are appropriate candidates for a
      continuous OC as a contraceptive, the approved indication for this medication.

PMID- 22152589
TI  - Assessment of predictive ability of Epworth scoring in screening of patients with
      sleep apnoea.
AB  - METHOD: Numerous studies have considered the benefits, and the disadvantages, of
      the Epworth Sleepiness Scale. Following an extensive literature review, we found
      that the evidence was inconclusive as regards the diagnostic efficacy of Epworth
      scoring for obstructive sleep apnoea syndrome. We undertook a retrospective study
      of 343 patients who underwent a sleep assessment over a 10-year period at the
      Monklands Hospital. ANALYSIS AND RESULTS: A total of 238 patients did not have
      sleep apnoea whereas 105 patients did. The mean Epworth score in patients with
      obstructive sleep apnoea syndrome was 10.94 (95 per cent confidence interval 9.46
      11.42), and in the non-apnoeic group it was 7.73 (95 per cent confidence interval
      7.04-8.41). Logistic regression and receiver operating characteristic curves were
      used to assess the predictive ability of Epworth scoring. The scores only
      explained 7-10 per cent of the variation in the probability of occurrence of
      obstructive sleep apnoea syndrome. The odds ratio for Epworth scoring was 1.118,
      and only 69 per cent of cases were correctly classified by the Scale.
      CONCLUSIONS: The literature review suggested that the Epworth Sleepiness Scale is
      associated with a low effect size and/or low predictive value when correlated or
      regressed on the Apnoea-Hypopnoea Index or Respiratory Disturbance Index, thus
      limiting its value as a screening test. Our study concluded that the Epworth
      Scale is only marginally useful in predicting the occurrence of obstructive sleep
      apnoea syndrome. We believe that every patient with a direct or witnessed history
      of sleep apnoea with obstructive symptoms have some form of sleep assessment.

PMID- 22152591
TI  - Effects of kiwifruit extracts on colonic gene and protein expression levels in IL
      10 gene-deficient mice.
AB  - Inflammatory bowel disease (IBD) is a collective term for conditions
      characterised by chronic inflammation of the gastrointestinal tract involving an
      inappropriate immune response to commensal micro-organisms in a genetically
      susceptible host. Previously, aqueous and ethyl acetate extracts of gold
      kiwifruit (Actinidia chinensis) or green kiwifruit (A. deliciosa) have
      demonstrated anti-inflammatory activity using in vitro models of IBD. The present
      study examined whether these kiwifruit extracts (KFE) had immune-modulating
      effects in vivo against inflammatory processes that are known to be increased in
      patients with IBD. KFE were used as a dietary intervention in IL-10-gene
      deficient (Il10(-/-)) mice (an in vivo model of IBD) and the C57BL/6J background
      strain in a 3 * 2 factorial design. While all Il10(-/-) mice developed
      significant colonic inflammation compared with C57BL/6J mice, this was not
      affected by the inclusion of KFE in the diet. These findings are in direct
      contrast to our previous study where KFE reduced inflammatory signalling in
      primary cells isolated from Il10(-/-) and C57BL/6J mice. Whole-genome gene and
      protein expression level profiling indicated that KFE influenced immune
      signalling pathways and metabolic processes within the colonic tissue; however,
      the effects were subtle. In particular, expression levels across gene sets
      related to adaptive immune pathways were significantly reduced using three of the
      four KFE in C57BL/6J mice. The present study highlights the importance of
      investigating food components identified by cell-based assays with appropriate in
      vivo models before making dietary recommendations, as a food that looks promising
      in vitro may not be effective in vivo.

PMID- 22152590
TI  - An exploratory factor analysis of nutritional biomarkers associated with major
      depression in pregnancy.
AB  - OBJECTIVE: Major depressive disorder (MDD) during pregnancy increases the risk of
      adverse maternal and infant outcomes. Maternal nutritional status may be a
      modifiable risk factor for antenatal depression. We evaluated the association
      between patterns in mid-pregnancy nutritional biomarkers and MDD. DESIGN:
      Prospective cohort study. SETTING: Pittsburgh, Pennsylvania, USA. SUBJECTS: Women
      who enrolled at <=20 weeks' gestation and had a diagnosis of MDD made with the
      Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of
      Mental Disorders, 4th edition) at 20-, 30- and 36-week study visits. A total of
      135 women contributed 345 person-visits. Non-fasting blood drawn at enrolment was
      assayed for red cell essential fatty acids, plasma folate, homocysteine and
      ascorbic acid; serum 25-hydroxyvitamin D, retinol, vitamin E, carotenoids,
      ferritin and soluble transferrin receptors. Nutritional biomarkers were entered
      into principal components analysis. RESULTS: Three factors emerged: Factor 1,
      Essential Fatty Acids; Factor 2, Micronutrients; and Factor 3, Carotenoids. MDD
      was prevalent in 21.5 % of women. In longitudinal multivariable logistic models,
      there was no association between the Essential Fatty Acids or Micronutrients
      pattern and MDD either before or after adjustment for employment, education or
      pre-pregnancy BMI. In unadjusted analysis, women with factor scores for
      Carotenoids in the middle and upper tertiles were 60 % less likely than women in
      the bottom tertile to have MDD during pregnancy, but after adjustment for
      confounders the associations were no longer statistically significant.
      CONCLUSIONS: While meaningful patterns were derived using nutritional biomarkers,
      significant associations with MDD were not observed in multivariable adjusted
      analyses. Larger, more diverse samples are needed to understand nutrition
      depression relationships during pregnancy.

PMID- 22152592
TI  - EXTUBATE: a randomised controlled trial of nasal biphasic positive airway
      pressure vs. nasal continuous positive airway pressure following extubation in
      infants less than 30 weeks' gestation: study protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Respiratory distress syndrome remains a significant problem among
      premature infants. Mechanical ventilation through an endotracheal tube remains
      the mainstay of respiratory support but may be associated with lung injury and
      the development of chronic lung disease of prematurity. Efforts are needed to
      reduce the duration of mechanical ventilation in favour of less invasive forms of
      respiratory support and to improve rates of successful extubation.Non-invasive
      respiratory support has been demonstrated to be less injurious to the premature
      lung. Standard practice is to use nasal continuous positive airway pressure (n
      CPAP) following extubation to support the baby's breathing. Many clinicians also
      use nasal biphasic positive airway pressure (n-BiPAP) in efforts to improve rates
      of successful extubation. However, there is currently no evidence that this
      confers any advantage over conventional nasal continuous positive airway
      pressure. METHODS: We propose an unblinded multi-centre randomised trial
      comparing n-CPAP with n-BiPAP in babies born before 30 weeks' gestation and less
      than two weeks old. Babies with congenital abnormalities and severe intra
      ventricular haemorrhage will be excluded. 540 babies admitted to neonatal centres
      in England will be randomised at the time of first extubation attempt. The
      primary aim of this study is to compare the rate of extubation failure within 48
      hours following the first attempt at extubation. The secondary aims are to
      compare the effect of n-BiPAP and n-CPAP on the following outcomes: 1.
      Maintenance of successful extubation for 7 days post extubation 2. Oxygen
      requirement at 28 days of age and at 36 weeks' corrected gestational age 3. Total
      days on ventilator, n-CPAP/n-BiPAP 4. Number of ventilator days following first
      extubation attempt 5. pH and partial pressure of carbon dioxide in the first post
      extubation blood gas 6. Duration of hospital stay 7. Rate of abdominal distension
      requiring cessation of feeds 8. Rate of apnoea and bradycardia 9. The age at
      transfer back to referral centre in days The trial will determine whether n-BiPAP
      is safe and superior to n-CPAP in preventing extubation failure in babies born
      before 30 weeks' gestation and less than two weeks old. TRIAL REGISTRATION
      NUMBER: ISRCTN: ISRCTN18921778.

PMID- 22152593
TI  - Modulation of phosphofructokinase (PFK) from Setaria cervi, a bovine filarial
      parasite, by different effectors and its interaction with some antifilarials.
AB  - BACKGROUND: Phosphofructokinase (ATP: D-fructose-6-phosphate-1
      phosphotransferase, EC 2.7.1.11, PFK) is of primary importance in the regulation
      of glycolytic flux. This enzyme has been extensively studied from mammalian
      sources but relatively less attention has been paid towards its characterization
      from filarial parasites. Furthermore, the information about the response of
      filarial PFK towards the anthelmintics/antifilarial compounds is lacking. In view
      of these facts, PFK from Setaria cervi, a bovine filarial parasite having
      similarity with that of human filarial worms, was isolated, purified and
      characterized. RESULTS: The S. cervi PFK was cytosolic in nature. The adult
      parasites (both female and male) contained more enzyme activity than the
      microfilarial (Mf) stage of S. cervi, which exhibited only 20% of total activity.
      The S. cervi PFK could be modulated by different nucleotides and the response of
      enzyme to these nucleotides was dependent on the concentrations of substrates (F
      6-P and ATP). The enzyme possessed wide specificity towards utilization of the
      nucleotides as phosphate group donors. S. cervi PFK showed the presence of thiol
      group(s) at the active site of the enzyme, which could be protected from
      inhibitory action of para-chloromercuribenzoate (p-CMB) up to about 76% by
      pretreatment with cysteine or beta-ME. The sensitivity of PFK from S. cervi
      towards antifilarials/anthelmintics was comparatively higher than that of
      mammalian PFK. With suramin, the Ki value for rat liver PFK was 40 times higher
      than PFK from S. cervi. CONCLUSIONS: The results indicate that the activity of
      filarial PFK may be modified by different effectors (such as nucleotides, thiol
      group reactants and anthelmintics) in filarial worms depending on the presence of
      varying concentrations of substrates (F-6-P and ATP) in the cellular milieu. It
      may possess thiol group at its active site responsible for catalysis. Relatively,
      40 times higher sensitivity of filarial PFK towards suramin as compared to the
      analogous enzyme from the mammalian system indicates that this enzyme could be
      exploited as a potential chemotherapeutic target against filariasis.

PMID- 22152594
TI  - Evidence of genetic susceptibility to infectious mononucleosis: a twin study.
AB  - Infectious mononucleosis is a clinical manifestation of primary Epstein-Barr
      virus infection. It is unknown whether genetic factors contribute to risk. To
      assess heritability, we compared disease concordance in monozygotic to dizygotic
      twin pairs from the population-based California Twin Program and assessed the
      risk to initially unaffected co-twins. One member of 611 and both members of 58
      twin pairs reported a history of infectious mononucleosis. Pairwise concordance
      in monozygotic and dizygotic pairs was respectively 12.1% [standard error
      (s.e.)=1.9%] and 6.1% (s.e.=1.2%). The relative risk (hazard ratio) of
      monozygotic compared to dizygotic unaffected co-twins of cases was 1.9 [95%
      confidence interval (CI) 1.1-3.4, P=0.03], over the follow-up period. When the
      analysis was restricted to same-sex twin pairs, that estimate was 2.5 (95% CI 1.2
      5.3, P=0.02). The results are compatible with a heritable contribution to the
      risk of infectious mononucleosis.

PMID- 22152596
TI  - Inuit housing and homelessness: results from the International Polar Year Inuit
      Health Survey 2007-2008.
AB  - OBJECTIVES: Evaluate housing characteristics across Inuit regions in Canada that
      participated in the 2007-2008 International Polar Year (IPY) Inuit Health Survey.
      STUDY DESIGN: A cross-sectional Inuit Health Survey. METHODS: Housing
      characteristics were ascertained as part of the IPY Inuit Health Survey through
      interviews conducted in 33 coastal and 3 inland communities, representing all
      communities in the Inuvialuit Settlement Region (ISR) of NWT, Nunavut and
      Nunatsiavut of northern Labrador. Variable descriptive statistics were weighted
      and presented by region and by whether children were present or not in each
      household. RESULTS: A total of 2,796 Inuit households were approached, of which
      68% participated (n=1,901 households). In ISR and Nunavut, approximately 20% of
      homes provided shelter to the homeless compared to 12% in Nunatsiavut (p<=0.05).
      The prevalence of public housing and household crowding also varied by region,
      with Nunavut having a statistically significantly higher prevalence of crowding
      (30%) than Nunatsiavut (12%) and ISR (12%). Household crowding was more prevalent
      among homes with children. Overall, 40% of homes were in need of major repairs
      and problems with mould were reported in 20% of households. CONCLUSIONS: Adequate
      shelter is a basic human need and an essential foundation for thriving population
      health. The results indicate that improvements in housing indicators are needed.
      Of utmost concern is the high prevalence of overcrowding in Inuit homes with
      children, which poses potential consequences for children's health and well
      being. Further, the high percentage of homes providing shelter to the homeless
      suggests that hidden homelessness needs to be addressed by further research and
      program implementation.

PMID- 22152597
TI  - The legacy of the Alaska Siberia Medical Research Program: a historical
      perspective.
AB  - BACKGROUND: The Alaska Siberia Medical Research Program was established at the
      University of Alaska (UA) at a time when there was no research funded by the
      National Institutes of Health (NIH) that was concerned with Alaska Native health
      issues. The program grew out of a dire need for an understanding of the
      apparently rapidly growing health problems in the Native community. The initial
      plan included the following objectives. OBJECTIVES: The objectives are to develop
      a self-sustaining infrastructure for biomedical research by gaining support from
      Alaska Natives, UA, national political leaders, NIH and the Russian Academy of
      Medical Science (RAMS); to identify researchers committed to helping Alaska
      Natives; to develop meaningful, Native-driven participatory research; to carry
      out necessary research to form the foundation for future research; and to develop
      circumpolar collaborations. RESULTS: The objectives were achieved because of the
      extraordinary and cheerful contributions by all participants in the program. The
      collaborative research resulted in some 70 published manuscripts identifying and
      characterizing research-neglected health problems. Unique risk factors for
      diabetes, cardiovascular disease, alcoholism and seasonal affective disorders
      were characterized and institutionalized prevention programs were established.
      The effort of the program led to U.S. Congressional action establishing the
      University of Alaska as a minority institution, leading to the funding of a
      variety of successful NIH-funded research centres and programs at the university
      that are concerned with Native health problems. CONCLUSION: A small, visionary
      investment by the University of Alaska for establishing the program led to a co
      operative effort by the UA, RAMS, Alaska Native Health communities and the NIH
      that resulted in the development of self-sustaining medical research efforts in
      Alaska and Siberia. The program spawned pilot studies, leading to NIH-funded
      research that has provided fundamental insights into the etiology of health
      problems and their reduction by research-based intervention and prevention
      programs.

PMID- 22152598
TI  - Changing dietary patterns and body mass index over time in Canadian Inuit
      communities.
AB  - OBJECTIVES: The International Polar Year (IPY) Inuit Health Survey provided an
      opportunity to compare dietary and body mass index (BMI) data with data collected
      a decade earlier for the same communities. STUDY DESIGN: A dietary survey
      included 1,929 randomly selected participants aged 15 years or older, selected
      from 18 Inuit communities in 1998-1999. The IPY survey included 2,595 randomly
      selected participants aged 18 years or older, selected from 36 Inuit communities
      in 2007-2008. Data from the same 18 communities included in both surveys were
      compared for adults 20 years and older. METHODS: Twenty-four-hour dietary recall
      data were analysed to assess the percentage of energy from traditional and market
      foods by sex and age groups. Body mass index (BMI) was assessed to establish the
      prevalence of obesity by sex and age groups in both surveys. RESULTS: There was a
      significant decrease (p<=0.05) in energy contribution from traditional food and a
      significant increase in market food consumption over time. Sugar-sweetened
      beverages, chips and pasta all increased as percentages of energy. BMI increased
      overall for women and for each age stratum evaluated (p<0.05). CONCLUSION: The
      nutrition transition continues in the Canadian Arctic with a concurrent increase
      in BMI.

PMID- 22152600
TI  - First trimester myomectomy as an alternative to termination of pregnancy in a
      woman with a symptomatic uterine leiomyoma: a case report.
AB  - INTRODUCTION: Performing a myomectomy during pregnancy is extremely rare due to
      the risk of pregnancy loss, hemorrhage and hysterectomy. Favorable outcomes have
      been demonstrated with select second trimester gravid myomectomies. Literature
      documenting first trimester surgical management of myomas during pregnancy is
      scant. Patients with symptomatic myomas failing conservative management in the
      first trimester may be counseled to abort the pregnancy and then undergo
      myomectomy. Reports focusing on myomectomy in the first trimester are needed to
      permit more thorough options counseling for patients failing conservative
      management in the first trimester. CASE PRESENTATION: A 30-year-old Caucasian
      primagravid (G1P0) was referred for termination of her pregnancy at 10 weeks due
      to a 14 cm myoma causing severe pain, constipation and urine retention. Her
      referring physician planned an interval myomectomy following the abortion.
      Instead, our patient underwent myomectomy at 11 weeks. Two leiomyomas were
      successfully removed; she delivered a healthy infant at term. CONCLUSION:
      Patients in the first trimester should not be counseled that termination followed
      by myomectomy is the best option for symptomatic myomas, failing conservative
      treatment. Management should be individualized after taking into account the
      patient's symptoms, gestational age and the location of the myomas in relation to
      the placenta. Any field providing women's health services will be impacted by the
      ability to offer more thorough options counseling for women with refractory
      myomas in the first trimester.

PMID- 22152601
TI  - Technique for chest compressions in adult CPR.
AB  - Chest compressions have saved the lives of countless patients in cardiac arrest
      as they generate a small but critical amount of blood flow to the heart and
      brain. This is achieved by direct cardiac massage as well as a thoracic pump
      mechanism. In order to optimize blood flow excellent chest compression technique
      is critical. Thus, the quality of the delivered chest compressions is a pivotal
      determinant of successful resuscitation. If a patient is found unresponsive
      without a definite pulse or normal breathing then the responder should assume
      that this patient is in cardiac arrest, activate the emergency response system
      and immediately start chest compressions. Contra-indications to starting chest
      compressions include a valid Do Not Attempt Resuscitation Order. Optimal
      technique for adult chest compressions includes positioning the patient supine,
      and pushing hard and fast over the center of the chest with the outstretched arms
      perpendicular to the patient's chest. The rate should be at least 100
      compressions per minute and any interruptions should be minimized to achieve a
      minimum of 60 actually delivered compressions per minute. Aggressive rotation of
      compressors prevents decline of chest compression quality due to fatigue. Chest
      compressions are terminated following return of spontaneous circulation.
      Unconscious patients with normal breathing are placed in the recovery position.
      If there is no return of spontaneous circulation, then the decision to terminate
      chest compressions is based on the clinical judgment that the patient's cardiac
      arrest is unresponsive to treatment. Finally, it is important that family and
      patients' loved ones who witness chest compressions be treated with consideration
      and sensitivity.

PMID- 22152602
TI  - Introduction: heartworm.

PMID- 22152603
TI  - Macrocyclic lactones and Dirofilaria immitis microfilariae.
AB  - Although there has been extensive veterinary focus on both the effectiveness of
      macrocyclic lactones for heartworm prevention in dogs and their adulticidal
      effects, little attention has been directed to their effects on heartworm
      microfilariae. With routine use of macrocyclic lactones, in some cases knowingly,
      in dogs with existing heartworm infections, veterinarians should recognize the
      benefits, and possible complications, arising from this behavior. Macrocyclic
      lactones remain our only class of heartworm prevention available, and preserving
      their effectiveness is critical. Drugs in this class share common traits: there
      are currently no Food and Drug Administration-approved microfilaricides in the US
      marketplace, but because all macrocyclic lactones have microfilaricidal
      properties (to varying degrees), they are widely used by veterinarians for this
      purpose. Originally formulated to be used in dogs without patent heartworm
      infections, all have been demonstrated as safe to use at label doses, and higher,
      in microfilaremic dogs. All of the product labels indicate that dogs should be
      tested for heartworm infection before starting preventive therapy. Although
      microfilaricidal, microfilariae reduction may take many months to occur, and some
      dogs may never clear. The effects of macrocyclic lactones on the numbers of
      circulating microfilariae may be due to several different underlying causes
      (i.e., direct effect on the nervous system, affecting stages found in the uterus
      of the female worms), but the details of all mechanisms by which microfilariae
      are killed and/or cleared in dogs treated with macrocyclic lactones have not yet
      been fully elucidated. Some 10% to 20% of heartworm-infected dogs that begin
      monthly heartworm preventive treatment without adulticide therapy will have the
      continued and persistent presence of circulating microfilariae, and the concern
      is that this may be selecting for resistance to these molecules. The veterinary
      literature now includes evidence of increased genotypic homozygosity in specific
      dogs in one area of the country for a marker gene associated with macrocyclic
      lactone resistance in nematodes of ruminants. This article will review the
      biology of microfilariae, as well as the evolution of diagnostic testing for
      heartworm infection. The effects of macrocyclic lactones on microfilaria behavior
      and survival will be discussed, as well as the use and effects of macrocyclic
      lactones in microfilaremic dogs, with or without adulticide treatment. The effect
      of doxycycline on heartworm microfilariae, optimal testing methodologies, and
      verification of effective clearance of microfilariae after adulticide treatment
      and microfilaricidal therapy so that dogs do not remain a potential source of
      infection for other dogs are all covered.

PMID- 22152604
TI  - Introduction to the alpha-proteobacteria: Wolbachia and Bartonella, Rickettsia,
      Brucella, Ehrlichia, and Anaplasma.
AB  - Wolbachia is an obligate intracellular endosymbiont and likely mutualist living
      within the heartworm Dirofilaria immitis and a number of other filarial nematodes
      in the family Onchocercidae. The bacterial infection is passed from worm to worm
      transovarially; the organisms are in ovarian cells, the developing microfilariae,
      and multiply and persist in all later developmental stages through the mosquito
      and into the next host. Besides being present in the ovaries of the adult worms,
      they also are present in large numbers within the hypodermal tissues of the
      nematode. It is now know that these bacteria that were first observed in
      heartworms more than 30 years ago are actually related to similar Wolbachia
      bacteria that are found in arthropods. Wolbachia is an alpha-proteobacteria, and
      this group includes a number of important arthropod-transmitted bacterial agents
      of dogs and cats: Rickettsia rickettsii, R. felis, Anaplasma platys, Ehrlichia
      canis, E. chaffeensis, and E. ewingii. Alpha-proteobacteria are also important as
      obligate intracellular mutualists in plants in which they are responsible for
      nitrogen fixation. Recent work on the treatment of heartworms in dogs with
      doxycycline stems from related work with the human filarial nematode Onchocerca
      volvulus that causes river blindness in people.

PMID- 22152605
TI  - Mosquito vectors of dog heartworm in the United States: vector status and factors
      influencing transmission efficiency.
AB  - Dog heartworm (Dirofilaria immitis) is dependent on mosquito vectors for its
      maintenance and transmission among vertebrate hosts. Consequently, D. immitis
      abundance and distribution are closely linked with mosquito vector biology and
      ecology. Information on the important dog heartworm vectors in the United States
      is limited and no comprehensive surveillance of dog heartworm in US mosquitoes
      has been undertaken to date. Here, we review information gleaned from a number of
      field surveys documenting heartworm presence in wild mosquito populations as well
      as laboratory assessments of mosquito vector capacity. Various biological and
      ecological factors likely contribute to the relative importance of different
      vector species. We describe some of these factors, rank the leading criteria for
      efficient vectors, and present the most likely vector species found across the
      United States. Considering the recent emergence of drug resistance among D.
      immitis strains, practical knowledge of heartworm vector biology and control
      should be incorporated into heartworm disease management programs. We conclude by
      proposing that heartworm control would benefit by targeting mosquito vectors, and
      we suggest ways in which veterinarians can incorporate the recognition of vector
      importance into heartworm prevention recommendations imparted to clients.

PMID- 22152606
TI  - Evidence for macrocyclic lactone anthelmintic resistance in Dirofilaria immitis.
AB  - Reports of loss-of-efficacy (LOE) events in dogs infected with Dirofilaria
      immitis despite adherence to accepted prophylaxis regimens with a macrocyclic
      lactone anthelmintic are attracting considerable attention. It is crucially
      important to distinguish among several possible causes for these LOE reports, one
      of which is the evolution of resistance to these drugs in heartworms. We review
      here recent evidence at the molecular level that supports the hypothesis that
      parasites derived from LOE cases have experienced a strong selection event and
      that these populations are characterized by very high frequencies of single
      nucleotide polymorphisms in a D. immitis gene encoding a P-glycoprotein
      transporter, comprised of homozygous guanosine residues at 2 locations ("GG-GG"
      genotype). Furthermore, an infected dog adopted to Canada from the southern
      United States harbored a microfilarial population that was insensitive to very
      high doses of macrocyclic lactones and was characterized by a high frequency of
      the GG-GG genotype associated with LOE cases. We propose that this case be
      defined as a drug-resistant heartworm infection and suggest that a simple assay
      for the existence of resistant parasites is a 7-day microfilariae suppression
      test, which can be performed in a veterinary clinic as part of an effort to
      document the geographic distribution of this phenotype.

PMID- 22152607
TI  - Heartworm genomics: unprecedented opportunities for fundamental molecular
      insights and new intervention strategies.
AB  - Vector-borne diseases, including canine heartworm disease (CHWD), are of major
      socioeconomic and canine health importance worldwide. Although many studies have
      provided insights into CHWD, to date there has been limited study of fundamental
      molecular aspects of Dirofilaria immitis itself, its relationship with the canine
      host, its vectors, as well as the potential of drug resistance to emerge, using
      advanced -omic technologies. This article takes a prospective view of the
      benefits that advanced -omics technologies will have toward understanding D.
      immitis and CHWD. Tackling key biological questions using these technologies will
      provide a "systems biology" context and could lead to radically new intervention
      and management strategies against heartworm.

PMID- 22152608
TI  - Expression of silent mating type information regulator 2 homolog 1 and its role
      in human intervertebral disc cell homeostasis.
AB  - INTRODUCTION: Intervertebral disc tissue homeostasis is modulated by a variety of
      molecules. Silent mating type information regulator 2 homolog 1 (SIRT1) plays a
      key role in various physiological processes. The aim of the present study was to
      verify the expression of SIRT1 and determine SIRT1 function in human
      intervertebral disc cell homeostasis. METHODS: Human nucleus pulposus (NP) cells
      were obtained from 24 surgical patients (mean age: 39.4 years) and monolayer
      cultured. SIRT1 expression was investigated using RT-PCR analysis and
      immunohistochemical staining. Quantitative real-time RT-PCR was performed to
      detect mRNA expression of SIRT1 and other genes: aggrecan, collagen type 2 and
      Sox9. The effect of SIRT1 on the extracellular matrix metabolism of NP cells was
      examined using recombinant human SIRT1 protein and a protein delivery reagent.
      Cell number and proliferation activity were measured following SIRT1 treatment.
      To reveal the deacetylation potential of transfected recombinant human SIRT1,
      western blotting for acetylated p53 was utilized. R-phycoerythrin was used for
      the negative control. RESULTS: SIRT1 expression was confirmed at both mRNA and
      protein levels in almost all NP cells. Real-time RT-PCR analysis showed SIRT1
      mRNA expression significantly increased with donor age (P <0.05, rho = 0.492).
      Pfirrmann grade 3 discs showed significantly higher SIRT1 mRNA expression than
      other grades. SIRT1 treatment significantly reduced aggrecan, Sox9 and collagen
      type 2 mRNA expression in a dose-dependent manner in all disease classes and disc
      degeneration grades. Proliferation activity was decreased by SIRT1 treatment in
      lumbar spinal stenosis and lumbar disc herniation, Pfirrmann grade 3 and grade 4
      discs. In contrast, it was significantly upregulated in idiopathic scoliosis,
      Pfirrmann grade 2 discs. The negative control protein did not affect
      extracellular matrix metabolism or proliferation activity. CONCLUSIONS: We
      demonstrate for the first time that SIRT1 is expressed by human NP cells. SIRT1
      expression was significantly elevated in an early degeneration stage. SIRT1
      affected both extracellular matrix metabolism and proliferation activity; the
      effect of SIRT1 was altered according to disease class and disc degeneration
      grade. SIRT1 appears to play a key role in homeostasis during the human
      intervertebral disc degeneration process.

PMID- 22152609
TI  - [Muir-Torre syndrome with conserved expression of MLH1, MSH2 and MSH6].

PMID- 22152611
TI  - Outcome of endodontic surgery: a meta-analysis of the literature--Part 2:
      Comparison of endodontic microsurgical techniques with and without the use of
      higher magnification.
AB  - INTRODUCTION: The aim of this study was to investigate the outcome of root-end
      surgery. It identifies the effect of the surgical operating microscope or the
      endoscope on the prognosis of endodontic surgery. The specific outcomes of
      contemporary root-end surgery techniques with microinstruments but only loupes or
      no visualization aids (contemporary root-end surgery [CRS]) were compared with
      endodontic microsurgery using the same instruments and materials but with high
      power magnification as provided by the surgical operating microscope or the
      endoscope (endodontic microsurgery [EMS]). The probabilities of success for a
      comparison of the 2 techniques were determined by means of a meta-analysis and
      systematic review of the literature. The influence of the tooth type on the
      outcome was investigated. METHODS: A comprehensive literature search for
      longitudinal studies on the outcome of root-end surgery was conducted. Three
      electronic databases (ie, Medline, Embase, and PubMed) were searched to identify
      human studies from 1966 up to October 2009 in 5 different languages (ie, English,
      French, German, Italian, and Spanish). Review articles and relevant articles were
      searched for cross-references. In addition, 5 dental and medical journals (ie,
      Journal of Endodontics, International Endodontic Journal, Oral Surgery Oral
      Medicine Oral Pathology Oral Radiology and Endodontics, Journal of Oral and
      Maxillofacial Surgery, and International Journal of Oral and Maxillofacial
      Surgery) dating back to 1975 were hand searched. Following predefined inclusion
      and exclusion criteria, all articles were screened by 3 independent reviewers
      (S.B.S., M.R.K., and F.C.S.). Relevant articles were obtained in full-text form,
      and raw data were extracted independently by each reviewer. After agreement among
      the reviewers, articles that qualified were assigned to group CRS. Articles
      belonging to group EMS had already been obtained for part 1 of this meta
      analysis. Weighted pooled success rates and a relative risk assessment between
      CRS and EMS overall as well as for molars, premolars, and anteriors were
      calculated. A random-effects model was used for a comparison between the groups.
      RESULTS: One hundred one articles were identified and obtained for final
      analysis. In total, 14 studies qualified according to the inclusion and exclusion
      criteria, 2 being represented in both groups (7 for CRS [n = 610] and 9 for EMS
      [n = 699]). Weighted pooled success rates calculated from extracted raw data
      showed an 88% positive outcome for CRS (95% confidence interval, 0.8455-0.9164)
      and 94% for EMS (95% confidence interval, 0.8889-0.9816). This difference was
      statistically significant (P < .0005). Relative risk ratio analysis showed that
      the probability of success for EMS was 1.07 times the probability of success for
      CRS. Seven studies provided information on the individual tooth type (4 for CRS
      [n = 457] and 3 for EMS [n = 222]). The difference in probability of success
      between the groups was statistically significant for molars (n = 193, P = .011).
      No significant difference was found for the premolar or anterior group (premolar
      [n = 169], P = .404; anterior [n = 277], P = .715). CONCLUSIONS: The probability
      for success for EMS proved to be significantly greater than the probability for
      success for CRS, providing best available evidence on the influence of high-power
      magnification rendered by the dental operating microscope or the endoscope. Large
      scale randomized clinical trials for statistically valid conclusions for current
      endodontic questions are needed to make informed decisions for clinical practice.

PMID- 22152612
TI  - Ferrule effect: a literature review.
AB  - INTRODUCTION: Preserving intact coronal and radicular tooth structure, especially
      maintaining cervical tissue to create a ferrule effect, is considered to be
      crucial for the optimal biomechanical behavior of restored teeth. The ferrule
      effect has been extensively studied and still remains controversial from many
      perspectives. The purpose of this study was to summarize the results of research
      conducted on different issues related to the ferrule effect and published in peer
      reviewed journals listed in PubMed. METHODS: The search was conducted using the
      following key words: "ferrule" and "ferrule effect" alone or in combination with
      "literature review," "fracture resistance," "fatigue," "finite element analysis,"
      and "clinical trials." RESULTS: The findings from reviewed articles were
      categorized into three main categories: laboratory studies, computer simulation,
      and clinical trials. Laboratory studies were further classified into subchapters
      based on the main aspect investigated in relation to the ferrule effect.
      CONCLUSIONS: The presence of a 1.5- to 2-mm ferrule has a positive effect on
      fracture resistance of endodontically treated teeth. If the clinical situation
      does not permit a circumferential ferrule, an incomplete ferrule is considered a
      better option than a complete lack of ferrule. Including a ferrule in preparation
      design could lead to more favorable fracture patters. Providing an adequate
      ferrule lowers the impact of the post and core system, luting agents, and the
      final restoration on tooth performance. In teeth with no coronal structure, in
      order to provide a ferrule, orthodontic extrusion should be considered rather
      than surgical crown lengthening. If neither of the alternative methods for
      providing a ferrule can be performed, available evidence suggests that a poor
      clinical outcome is very likely.

PMID- 22152614
TI  - Prevalence of internal inflammatory root resorption.
AB  - INTRODUCTION: Internal inflammatory root resorption is regarded as rare because
      it is only occasionally detected in clinical or radiographic examination of
      teeth. However, inflammation is supposedly an important etiologic factor of
      internal resorption. Therefore, we tested the hypothesis that there is no
      difference in the presence of internal resorption between teeth with vital,
      healthy pulp and teeth with a history of pulp inflammation. METHODS: Thirty teeth
      with no previous root canal treatment that were to be sequentially extracted from
      adult patients were diagnosed for their pulpal status (ie, healthy, pulpitis, or
      necrosis). After extraction, the teeth were split buccolingually, and both halves
      were exposed to 6% sodium hypochlorite for 10 minutes under constant shaking to
      remove all organic debris covering the root canal walls. The specimens were
      washed in water and prepared for scanning electron microscopy to examine the root
      canals for the presence of internal resorption. RESULTS: The null hypothesis of
      this study was rejected. None of the 9 teeth with healthy pulps revealed signs of
      internal resorption. Four of the 8 teeth with pulpitis (50%) and 10 of the 13
      teeth with necrotic pulps (77%) had internal resorption (P < .01). The average
      number of resorptive lesions in the affected necrotic teeth was 2.4, whereas in
      teeth with pulpitis and internal resorption, the average number of lesions was
      1.25. The amount of resorption was always <100-MUm deep; the length of the
      lesions varied from 200 MUm to >1 mm. Most lesions (15) were detected in the
      middle third of the root, followed by the apical third (13). Only 1 internal
      resorptive lesion was detected in the coronal third of the root canal.
      CONCLUSIONS: Internal resorption was a frequent finding in teeth with pulp
      inflammation or necrosis.

PMID- 22152613
TI  - Hemostasis control in endodontic surgery: a comparative study of calcium sulfate
      versus gauzes and versus ferric sulfate.
AB  - INTRODUCTION: Calcium sulfate (CaS) is a simple, biocompatible material with a
      long history of safe use in different fields of medicine. CaS is a rapidly
      resorbing material that leaves behind a calcium phosphate lattice, which promotes
      bone regeneration and hemostasis. The aim of this study was a clinical evaluation
      of the hemostatic effect of CaS hemi-hydrate (CaSO4), commonly known as plaster
      of Paris, in endodontic surgery. METHODS: Twenty-four patients with 31
      periradicular lesions were enrolled in this study. The apical roots were exposed,
      and the bleeding would have made it difficult to correctly fill the root-end
      cavities. To avoid such an inconvenience, the teeth were divided into 3 groups.
      Hemostasis was attempted by using CaS in 11 teeth (group I), gauze tamponade in
      another 10 teeth (group II), or 20% ferric sulfate in the last 10 teeth (group
      III). RESULTS: Control of the bleeding was achieved in all teeth of group I,
      whereas in group II adequate hemostasis was achieved in 3 of 10 cases and in
      group III in 6 of 10 cases. CONCLUSIONS: The use of CaS completely eliminated the
      bleeding, with a very good level of hemostasis.

PMID- 22152610
TI  - [Decrease in hospitalizations due to polyvalent medical day hospital].
AB  - INTRODUCTION: The day hospital is an alternative to hospitalization. This
      alternative improves accessibility and comfort of the patients, and avoids
      hospitalizations. Nevertheless, the efficacy of the polyvalent medical day
      hospital in avoiding hospitalizations has not been evaluated. OBJECTIVE: To
      analyze hospital stays avoided by the polyvalent medical day hospital of a
      university hospital of the Andalusian Health Service. METHODS: An observational
      prospective study of the patients studied and/or treated in the polyvalent
      medical day hospital of the Hospital Universitario Puerto Real over a one year
      period. RESULTS: A total of 9640 patients were attended to, with 1413 procedures
      and 4921 i.v. treatments. There were 3182 visits to the priority consultation of
      the polyvalent medical day hospital. The most frequent consultation complaints
      were constitutional symptoms (15.9%) and anemia (14.5%). After the first visit,
      21.5% of the patients were discharged and fewer than 3% were hospitalized.
      Hospitalization was avoided in 16.8% of the patients, there being a 6.0% decrease
      in the need for hospital beds (5.0% reduction in the internal medicine unit).
      Inadequate hospitalizations and 30-day readmissions decreased 93.3% and 4.2%,
      respectively. The most frequent diagnosis was neoplasm (26.0%), and most of the
      beds freed up were generated by patients diagnosed of neoplasm (26.7%).
      CONCLUSION: With this type of polyvalent medical day hospital, we have observed
      improved efficiency of health care, freeing up hospital beds by reducing
      hospitalizations, inadequate hospitalizations and re-admissions in the medical
      units involved.

PMID- 22152615
TI  - Measuring bone density in healing periapical lesions by using cone beam computed
      tomography: a clinical investigation.
AB  - INTRODUCTION: Differences in bone density before and after endodontic treatment
      were examined in teeth with periapical lesions in Hounsfield units (HUs) by using
      cone beam computed tomography (CBCT). METHODS: Sixteen patients requiring
      endodontic treatment for periapical lesions underwent CBCT scan before and after
      treatment. Their bone densities were calculated in HUs. The study included 16
      lesions measuring 8-10 mm in diameter. HU measurements were taken from an area of
      2.25 mm(2) on the CBCT images where the bone density was lowest, before and after
      treatment. RESULTS: The initial and final measurements were compared
      statistically by using paired samples statistics at the 5% significance level.
      CONCLUSIONS: The results of this study support the use of CBCT to measure bone
      density before and after endodontic treatment.

PMID- 22152616
TI  - Postoperative pain after manual and mechanical glide path: a randomized clinical
      trial.
AB  - INTRODUCTION: This prospective randomized clinical trial evaluated the incidence
      of postoperative pain after glide path performed with PathFile (PF) (Dentsply
      Maillefer, Ballaigues, Switzerland) versus stainless-steel K-file (KF). METHODS:
      In 149 subjects, the mechanical glide path was performed with nickel-titanium
      (NiTi) rotary PF; in 146 subjects, the manual glide path was performed with
      stainless-steel KFs. Postoperative pain, analgesics consumption, and the number
      of days to complete pain resolution were evaluated in the following 7 days. An
      analysis of variance model for repeated measures was used to compare the
      variation of pain-scale values (P < .05). The Student's t test for continuous
      variables normally distributed, the nonparametric Mann-Whitney U test for the
      nonnormally distributed variables, and the chi-square test for dichotomous
      variables were used (P < .05). Despite homogeneous baseline conditions at
      diagnosis, tooth type, pain prevalence, and scores, the postoperative pain
      prevalence curves in PF group evidenced a more favorable trend in terms of time
      to pain resolution compared with the KF group (P = .004). The difference was also
      evident in the model adjusted for analgesics consumption in both groups (P =
      .012). The mean analgesics intake per subject was significantly higher in the KF
      group (3.7 +/- 2.2) compared with the PF group (2 +/- 1.7) (P < .001). Mean pain
      stop values were also significantly higher in the KF group (2.7) compared with
      the PF group (1.7) (P = .001). CONCLUSIONS: The glide path with NiTi Rotary PF
      leads to less postoperative pain and faster symptom resolution.

PMID- 22152617
TI  - Irrigation trends among American Association of Endodontists members: a web-based
      survey.
AB  - INTRODUCTION: The purpose of this study was to determine current trends in
      irrigation selection among endodontists. METHODS: An invitation to participate in
      a web-based survey (QuestionPro) was e-mailed to 3844 members of the American
      Association of Endodontists. Survey participants were asked between 10 and 14
      questions based on their individual responses. Among other questions,
      participants were asked about their irrigant selection, irrigant concentration,
      smear layer removal, and use of adjuncts to irrigation. RESULTS: A total of 3707
      survey invitations were successfully delivered by e-mail after accounting for
      several undeliverable e-mail invitations. There were 1102 participants, with an
      overall completion rate of 28.5% (n = 1054). Our data indicate that >90% of
      respondents primarily use sodium hypochlorite, with 57% of them using it at a
      concentration >5.0%. Seventy-seven percent of respondents aim to remove the smear
      layer during endodontic treatment. At least 45% of respondents reported using an
      adjunct to irrigation. CONCLUSIONS: Most of the respondents are using full
      strength sodium hypochlorite and are routinely removing the smear layer during
      endodontic treatment. In addition, almost half of the respondents are using an
      adjunct, such as ultrasonic activation, to aid in their irrigation technique.

PMID- 22152618
TI  - Incidence and impact of painful exacerbations in a cohort with post-treatment
      persistent endodontic lesions.
AB  - INTRODUCTION: Painful exacerbations of persistent periapical lesions have unknown
      incidence and impact on quality of life. This study examined the incidence and
      impact of painful exacerbations and evaluated potential predictive factors of
      pain associated with root-filled teeth with persistent lesions after root canal
      treatment. METHODS: Patients from a university hospital clinic were screened to
      identify root-filled teeth with periapical lesions at time of treatment and not
      resolved at least 4 years later. A clinical and radiographic examination and
      questionnaire survey were conducted. Patient and treatment characteristics and
      details of pain experience were studied. Statistical analysis was carried out by
      using SPSS (version 18). RESULTS: One hundred twenty-seven patients with 185
      persistent lesions were recruited. Median age of patients at recruitment was 56
      years (range, 21-82 years). Median time since treatment was 5 years (range, 4-38
      years). Overall incidence of flare-up (requiring an unscheduled dental visit) was
      only 5.8% 20 years after treatment. Less severe pain was more frequent, with a
      combined incidence of 45% pain at 20 years after treatment. Female patients (odds
      ratio [OR], 2.6; 95% confidence interval [CI], 1.2-6.0; P < .05), treatment
      involving a mandibular molar or maxillary premolar (OR, 3.7; 95% CI, 1.6-8.6; P <
      .05), and preoperative pain (OR, 2.9; 95% CI, 1.3-6.7; P < .05) were
      significantly associated with pain after treatment. The most commonly affected
      activities during painful exacerbations were eating and tooth brushing, with
      minimal impact on daily living. CONCLUSIONS: The risk of flare-up among
      persistent lesions was very low. A lower degree of pain was more common, but
      generally with minimal impact on daily activities.

PMID- 22152620
TI  - Characteristics and dimensions of the Schneiderian membrane and apical bone in
      maxillary molars referred for apical surgery: a comparative radiographic analysis
      using limited cone beam computed tomography.
AB  - INTRODUCTION: The purpose of the present study was to evaluate the thickness and
      the anatomic characteristics of the Schneiderian membrane and cortical bone using
      limited cone beam computed tomography (CBCT) scannning in patients referred for
      planning of apical surgery of maxillary molars. METHODS: This controlled study
      included 2 cohorts of patients (n = 50 for each group). For patients in group 1
      (with apical pathology), 3 measurements in millimeters were performed using
      coronal and sagittal CBCT slices: the dimension of the apical lesion in the axis
      of the root, the width of the cortical bone in the axis of the root, and the
      thickness of the Schneiderian membrane perpendicular to the underlying cortical
      bone. For the analysis of CBCT scans of group 2 (without apical pathologies), 2
      measurements were performed using coronal and sagittal CBCT slices: the width of
      the cortical bone in the axis of the root and the thickness of the Schneiderian
      membrane perpendicular to the underlying cortical bone. RESULTS: For group 1, the
      periapical lesions evaluated measured between 0.27 and 7.41 mm in diameter, the
      apical bone separating the apical lesions from the maxillary sinus ranged from
      0.13 to 7.83 mm, and the dimensions of the Schneiderian membrane ranged from 0.25
      to 13.98 mm. The apical bone was generally thicker in patients with periapical
      lesions. Regarding the dimensions of the Schneiderian membrane, the values were
      statistically significantly higher for the patients in group 1 compared with
      group 2. CONCLUSIONS: The study showed that the Schneiderian membrane in the
      vicinity of roots with apical lesions tends to be significantly thicker when
      compared with the roots of teeth without apical pathoses.

PMID- 22152619
TI  - Significance of human cytomegalovirus and Epstein-Barr virus in inducing cytokine
      expression in periapical lesions.
AB  - INTRODUCTION: Because herpesviruses might be etiologically involved in periapical
      pathosis of endodontic origin, this study aimed to determine the occurrence of
      human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and the expression of
      mRNA transcripts of tumor necrosis factor (TNF)-alpha, gamma-interferon (IFN),
      interleukin (IL)-1beta, IL-6, IL-12, and IL-10 in periapical granulomatous
      lesions collected in conjunction with apicoectomy. METHODS: A total of 9
      symptomatic and 6 asymptomatic teeth with periapical lesions were studied.
      Periapical samples were collected in conjunction with apicoectomy, which was
      being performed because of radiographic evidence of incomplete periapical healing
      after conventional root canal therapy. By using established polymerase chain
      reaction primers and procedures, polymerase chain reaction assays were used to
      identify herpesvirus and cytokine gene expression. RESULTS: The difference in
      occurrence of HCMV, EBV, and cytokines between symptomatic and asymptomatic
      periapical lesions was statistically significant: HCMV (P = .048), EBV (P =
      .002), IFN (P = .001), IL-1 (P = .012), IL-6 (P = .026), IL-10 (P = .026), IL-12
      (P = .012), and TNF (P < .001) (Mann-Whitney U test). There was a significant
      correlation between EBV, HCMV, and TNF, gamma-IFN, IL-1, and IL-12 in symptomatic
      periapical lesions (Spearman test). CONCLUSIONS: The present findings provide
      evidence of a putative role of HCMV and EBV in the pathogenesis of symptomatic
      periapical pathosis. The release of tissue-destructive cytokines might be of
      pathogenetic significance.

PMID- 22152621
TI  - Capsule locus polymorphism among distinct lineages of Enterococcus faecalis
      isolated from canals of root-filled teeth with periapical lesions.
AB  - INTRODUCTION: Although Enterococcus faecalis is a member of the normal
      microbiota, it is also a major cause of nosocomial infections. Some strains of E.
      faecalis produce capsule, which contributes to pathogenesis through evasion of
      host defenses, and its production is dependent on the capsule (cps) operon
      polymorphism. This study investigated cps locus polymorphism in distinct lineages
      of E. faecalis isolated from canals of root-filled teeth with periapical lesions.
      METHODS: Twenty-two E. faecalis isolates were evaluated regarding the cps operon
      polymorphism and genetic diversity. The 3 known CPS types were determined by
      polymerase chain reaction. This information was correlated with multilocus
      sequence typing data, which were used to define genetic lineages. RESULTS: cpsA
      and cpsB were the only detected genes within the cps operon in 62.5% of E.
      faecalis strains (14/22), indicative of genotype CPS 1, which lacks capsule
      expression. The essential genes in the cps operon for capsule production were
      detected in the remaining strains, whereas 3 belonged to genotype CPS 5 and 5
      strains to genotype CPS 2. A total of 14 sequence types (STs) were resolved in 22
      E. faecalis isolates. Comparison with the E. faecalis international multilocus
      sequence typing database revealed that 9 STs were previously found, and that the
      5 STs were novel. CONCLUSIONS: Certain E. faecalis genotypes from canals of root
      filled teeth with periapical lesions belong to lineages associated with capsule
      expression and production of multiple virulence factors, which might account for
      their increased pathogenic potential.

PMID- 22152622
TI  - Inhibition of endogenous dentin matrix metalloproteinases by
      ethylenediaminetetraacetic acid.
AB  - INTRODUCTION: Endogenous dentin matrix metalloproteinases (MMPs) contribute to
      extracellular collagen matrix degradation in hybrid layers after adhesive dentin
      bonding procedures. Endodontic irrigants, including chlorhexidine and
      ethylenediaminetetraacetic acid (EDTA), might help protect the hybrid layer from
      this process. The objective of the present study was to determine the exposure
      time necessary for EDTA to inactivate endogenous MMP activity in human dentin.
      METHODS: Dentin beams (2 * 1 * 3 mm) were prepared from mid-coronal dentin of
      extracted third molars. The beams were demineralized in 10 wt% phosphoric acid,
      which also activated endogenous MMPs, and were divided into 4 experimental groups
      on the basis of exposure time to 17% EDTA (0, 1, 2, or 5 minutes). A generic
      colorimetric MMP assay measured MMP activity via absorbance at 412 nm. Data were
      evaluated by Kruskal-Wallis analysis of variance, followed by Dunn pair-wise
      comparisons at alpha = 0.05. RESULTS: All exposure times resulted in significant
      inhibition (P < .001) compared with unexposed controls. Specifically, percent
      inhibition for 1-, 2-, and 5-minute exposure times was 55.1% +/- 21.5%, 72.8% +/-
      11.7%, and 74.7% +/- 19.7%, respectively. CONCLUSIONS: Seventeen percent EDTA
      significantly inhibits endogenous MMP activity of human dentin within 1-2
      minutes. This might minimize hybrid layer degradation after resin bonding
      procedures in the root canal space.

PMID- 22152623
TI  - Smad 1/5 is involved in bone morphogenetic protein-2-induced odontoblastic
      differentiation in human dental pulp cells.
AB  - INTRODUCTION: Bone morphogenetic protein-2 (BMP-2) is a member of the
      transforming growth factor-beta (TGF-beta) superfamily, which has a broad range
      of activities that affect many different cell types. Previous research has
      suggested that BMP-2 induces the differentiation of human dental pulp cells
      (DPCs) into odontoblast-like cells. However, the mechanism by which BMP-2 induces
      odontoblastic differentiation has not yet been established. In the present study,
      we examined the involvement of the BMP/Smad pathway in mediating odontoblastic
      differentiation in DPCs. METHODS: Levels of phosphorylated and unphosphorylated
      Smad1/5 were quantified by Western blot analysis in response to BMP-2 and the BMP
      signaling inhibitor noggin. Some nuclear translocation of Smad1/5 was also
      observed by immunofluorescence staining in isolated DPCs treated with BMP-2. The
      effects of noggin on the BMP-2-induced odontoblastic differentiation of DPCs were
      determined by alkaline phosphatase activity assay, and the expression of
      odontoblastic markers was evaluated by reverse transcription polymerase chain
      reaction analysis and Western blotting. RESULTS: We found that BMP-2 induced the
      phosphorylation and nuclear translocation of Smad 1/5. In addition, noggin
      significantly inhibited alkaline phosphatase activity and odontoblastic
      differentiation and reduced the formation of mineralized nodules in BMP-2-treated
      DPCs. CONCLUSIONS: These findings suggest that Smad 1/5 is involved in BMP-2
      induced odontoblastic differentiation in DPCs.

PMID- 22152624
TI  - Effect of vanadium chloroperoxidase on Enterococcus faecalis biofilms.
AB  - INTRODUCTION: The aim of this study was to explore the antimicrobial effect of
      vanadium chloroperoxidase (VCPO) reaction products on Enterococcus faecalis
      biofilms of 4 different strains. METHODS: Twenty-four-hour biofilms of E.
      faecalis strains V583, ER5/1, E2, and OS-16 were incubated in mixtures with VCPO,
      halide (either bromide or chloride), and hydrogen peroxide. The antibacterial
      efficacy was assessed by colony-forming unit counts. RESULTS: The VCPO reaction
      products had a similar efficacy in reducing the viability of the 4 strains of E.
      faecalis (94%; range, 87%-100%). Bromide as the halogen of choice was more
      effective on E. faecalis strains E2 and OS-16, as compared with chloride (Mann
      Whitney U test; P < .05). Despite different quantities of produced biofilms by
      the 4 strains, VCPO treatment was similarly effective toward all strains (Kruskal
      Wallis test; P < .05). CONCLUSIONS: VCPO treatment results in an antimicrobial
      effect toward in vitro E. faecalis biofilms and might provide an addition to
      current endodontic treatment, possibly as an antimicrobial dressing.

PMID- 22152625
TI  - Dentin matrix protein-1 activates dental pulp fibroblasts.
AB  - INTRODUCTION: Dentin matrix protein-1 (DMP-1) is involved in the mineralization
      of hard dental tissues. DMP-1 is localized in several soft tissues, but its role
      is unclear. METHODS: Human inflamed dental pulps were collected from the
      endodontic clinic and human normal pulps from impacted teeth. Dental pulp cells
      from 8 subjects were explanted to test the effect of DMP-1 on interleukin-6 (IL
      6) and IL-8 production by using enzyme-linked immunosorbent assay. RESULTS: DMP-1
      was localized in pulp inflammation by using immunohistochemistry but was not
      present in impacted root pulps. Wherever found, areas of calcification were
      positively stained against DMP-1, suggesting its possible involvement in pulp
      inflammation and in pathologic calcification. To test this hypothesis, primary
      human pulp fibroblasts were cultured. The fibroblasts were identified on the
      basis of their morphology, immunoreactivity against vimentin and collagen 1a1 by
      immunofluorescence and negative staining to CD45, CD34, and cytokeratin by flow
      cytometry. DMP-1 (10 ng/mL) stimulated the production of IL-6 and IL-8 from pulp
      fibroblasts. DMP-1 showed an additive effect with lipopolysaccharide in IL-6 and
      IL-8 production. Inhibition of the p38 mitogen-activated protein kinase pathway
      blocked the proinflammatory effect of DMP-1 on pulp fibroblasts. CONCLUSIONS: Our
      data indicate that DMP-1 might participate in the development of inflammatory
      changes in the dental pulp. DMP-1 inhibition might be a new therapeutic strategy
      to target pulp inflammation and pathologic calcification.

PMID- 22152626
TI  - N-acetylcysteine inhibits growth and eradicates biofilm of Enterococcus faecalis.
AB  - INTRODUCTION: The aims of this study were to evaluate the antibacterial and
      biofilm eradication efficacies of N-acetylcysteine (NAC) on Enterococcus
      faecalis. METHODS: The minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) of NAC on E. faecalis were determined. In
      addition, the ability of dentin powder to neutralize the antibacterial activity
      of NAC was examined. Calcium hydroxide, a commonly used intracanal medicament,
      was included as a comparison. The efficacy of NAC on E. faecalis biofilms was
      tested by exposure of 21-day old E. faecalis biofilms to NAC. RESULTS: NAC was
      most bactericidal at pH 11 with MIC and MBC of 1.56 mg/mL and 12.5 mg/mL,
      respectively. Although preincubation of calcium hydroxide with dentin powder
      abolished its antibacterial effects, NAC completely killed E. faecalis regardless
      of dentin powder preincubation. In addition, prolonged incubation of NAC with
      dentin powder (up to 3 weeks) did not significantly reduce its antibacterial
      activity on E. faecalis. Furthermore, NAC also effectively eradicated E. faecalis
      biofilms. CONCLUSIONS: NAC was bactericidal against both the planktonic and
      biofilm forms of E. faecalis. This antibacterial property of NAC was unaffected
      by the presence of dentin.

PMID- 22152627
TI  - Behavioral effects of pulp exposure in mice lacking cannabinoid receptor 2.
AB  - INTRODUCTION: Cannabinoid receptor 2 (CB2) is an intriguing target for the
      treatment of pain because of its ability to mediate analgesia without
      psychoactive effects, but little is known about the role of CB2 in pain of
      endodontic origin. The purpose of this study was to determine the behavioral
      effects of dental pulp exposure in wild-type (WT) mice and to explore the
      contribution of CB2 to these behaviors using CB2 knockout (CB2 KO) mice. METHODS:
      Pulp exposures were created unilaterally in the maxillary and mandibular first
      molars of female WT and CB2 KO mice. The open field test was used before pulp
      exposure or sham surgery, and postoperatively at 1 day, 1 week, 2 weeks, and 3
      weeks. Mouse body weight and food consumption were recorded preoperatively and
      postoperatively at 1 day, 2 days, and 1 week. RESULTS: At baseline, CB2 KO mice
      weighed significantly more and had significantly greater food intake than WT
      mice. CB2 KO mice exhibited greater anxiety-like behavior in the baseline open
      field test, having significantly fewer center crossings and less distance
      traveled than WT mice. Pulp exposure had relatively little effect on the behavior
      of WT mice. CB2 KO mice with pulp exposures showed a decrease in food intake and
      body weight after surgery, and pulp exposure resulted in significantly fewer
      center crossings in the open field test in CB2 KO mice. CONCLUSIONS: Pulp
      exposure in CB2 KO mice resulted in behaviors consistent with an increase in pain
      and/or anxiety.

PMID- 22152628
TI  - Tissue reaction to a triantibiotic paste used for endodontic tissue self
      regeneration of nonvital immature permanent teeth.
AB  - INTRODUCTION: The endodontic regenerative procedure (ERP), which is an
      alternative to calcium hydroxide-induced apexification, involves the use of a
      triple antibiotic paste (TAP) as a dressing material. The aim of this study was
      to evaluate the response of rat subcutaneous tissue to implanted polyethylene
      tubes that were filled with TAP or calcium hydroxide. METHODS: Thirty rats
      received 2 individual implants of polyethylene tubes filled with TAP or calcium
      hydroxide paste (CHP) and another empty tube as a control. Thirty additional rats
      received 2 individual implants consisting of polyethylene tubes filled with
      dressing material carriers (macrogol and propylene glycol) and a sham procedure.
      After 7, 15, 30, 60, and 90 days, 12 animals were euthanized, and the tubes and
      surrounding tissue were removed and processed for histology by using glycol
      methacrylate and stained with hematoxylin and eosin. The histological score
      ranged from 0 to 3 depending on the content of inflammatory cells; the fibrous
      capsule was considered thin or thick, and necrosis and calcification were
      recorded as present or absent. The results were analyzed using the Kruskal-Wallis
      test. RESULTS: Both dressing materials induced moderate reactions at 7 and 15
      days. These reactions were similar to the control (P > .05) and reduced in
      intensity (to mild) from day 30 onward (P > .05). The carriers did not interfere
      with the reaction of the dressing materials. CONCLUSIONS: TAP and CHP were
      biocompatible over the different experimental periods examined.

PMID- 22152629
TI  - an in vitro study comparing the intracanal effectiveness of calcium hydroxide-
      and linezolid-based medicaments against Enterococcus faecalis.
AB  - INTRODUCTION: This study evaluated the efficacy of calcium hydroxide (CH),
      Vitapex (VP), linezolid (LZ), a combination of LZ with CH (LC), and a control
      group (N, no medicament) against Enterococcus faecalis (EF). METHODS: Human
      single-rooted premolars were instrumented up to ProTaper size F3 files. EF
      suspension was inoculated into each root specimen and incubated. The medicaments
      were syringed into each root by weight and incubated. After 72 hours, 6 samples
      per group (among the 5 groups) were retrieved. A hole was drilled on each root,
      and the dentinal shavings obtained were allowed to fall in brain-heart infusion
      (BHI) broth. Dilutions from the broth were plated and spread over BHI agar and
      blood agar. Colony-forming units (CFU) of EF were measured from BHI agar. The
      procedure was repeated after 8 days and 14 days. RESULTS: In group CH, the mean
      CFU (log 10 values) after 72 hours, 8 days, and 14 days were 1.17 +/- 1.16, 3.33
      +/- 1.97, and 4.17 +/- 1.17, respectively (statistically significant). In group
      VP, the mean CFU were 0.83 +/- 0.75, 4.00 +/- 1.67, and 4.83 +/- 1.72. In group
      LZ, the mean CFU at 72 hours and after 8 days was 0.17 +/- 0.41, and no CFU were
      found on the fourteenth day. Similarly, in group LC, the mean CFU at 72 hours and
      after 8 days was 0.50 +/- 0.84, which increased to 1.33 +/- 1.51 on the
      fourteenth day (not significant). CONCLUSIONS: LZ was found to be most effective
      on EF, followed by LC, CH, and VP.

PMID- 22152630
TI  - Root canal anatomy preservation of WaveOne reciprocating files with or without
      glide path.
AB  - INTRODUCTION: This study evaluated the influence of glide path on canal curvature
      and axis modification after instrumentation with WaveOne Primary reciprocating
      files. METHODS: Thirty ISO 15, 0.02 taper Endo Training Blocks were used. In
      group 1, glide path was created with PathFile 1, 2, and 3 at working length,
      whereas in group 2, glide path was not performed. In both groups, canals were
      shaped with WaveOne Primary reciprocating files at working length.
      Preinstrumentation and postinstrumentation digital images were superimposed and
      processed with Matlab r2010b software to analyze the curvature radius ratio (CRr)
      and the relative axis error (rAe), representing canal curvature modification.
      Data were analyzed with 1-way balanced analyses of variance at 2 levels (P <
      .05). RESULTS: Glide path was found to be extremely significant for both CRr
      parameter (F = 9.59; df = 1; P = .004) and rAe parameter (F = 13.55; df = 1; P =
      .001). CONCLUSIONS: Canal modifications seem to be significantly reduced when
      previous glide path is performed by using the new WaveOne nickel-titanium single
      file system.

PMID- 22152631
TI  - Metallurgical characterization of M-Wire nickel-titanium shape memory alloy used
      for endodontic rotary instruments during low-cycle fatigue.
AB  - INTRODUCTION: Rotary instruments made of a new nickel-titanium (NiTi) alloy (M
      Wire) have shown improved cyclic fatigue resistance and mechanical properties
      compared with those made of conventional superelastic NiTi wires. The objective
      of this study was to characterize microstructural changes of M-Wire throughout
      the cyclic fatigue process under controlled strain amplitude. METHODS: The
      average fatigue life was calculated from 30 M-Wire samples that were subjected to
      a strain-controlled (~ 4%) rotating bend fatigue test at room temperature and
      rotational speed of 300 rpm. Microstructural evolution of M-Wire has been
      investigated by different metallurgical characterization techniques, including
      differential scanning calorimetry, Vickers microhardness, and transmission
      electron microscopy at 4 different stages (as-received state, 30%, 60%, and 90%
      of average fatigue life). RESULTS: During rotating bend fatigue test, no
      statistically significant difference (P > .05) was found on austenite finish
      temperatures between as-received M-Wire and fatigued samples. However,
      significant differences (P < .05) were observed on Vickers microhardness for
      samples with 60% and 90% fatigue life compared with as-received and 30% fatigue
      life. Coincidentally, substantial growth of martensite grains and martensite
      twins was observed in microstructure under transmission electron microscopy after
      60% fatigue life. CONCLUSIONS: The results of the present study suggested that
      endodontic instruments manufactured with M-Wire are expected to have higher
      strength and wear resistance than similar instruments made of conventional
      superelastic NiTi wires because of its unique nano-crystalline martensitic
      microstructure.

PMID- 22152632
TI  - Comparison of cyclic fatigue resistance of three different rotary nickel-titanium
      instruments designed for retreatment.
AB  - INTRODUCTION: A number of rotary nickel-titanium (NiTi) systems have been
      developed to provide better, faster, and easier cleaning and shaping of the root
      canal system, and recently, rotary NiTi systems designed for root canal
      retreatment have been introduced. Because the main problem with the rotary NiTi
      files is fracture, the aim of this study was to compare the cyclic fatigue
      resistance of 3 different rotary NiTi systems designed for root canal
      retreatment. METHODS: Total of 60 instruments of 3 different rotary NiTi systems
      designed for root canal retreatment were used in this study. Twenty R-Endo R3, 20
      ProTaper D3, and 20 Mtwo R (Retreatment) 25.05 instruments were tested. Cyclic
      fatigue testing of instruments was performed by using a device that allowed the
      instruments to rotate freely inside an artificial canal. Each instrument was
      rotated until fracture occurred, and the number of cycles to fracture for each
      instrument was calculated. Representative samples were also evaluated under a
      scanning electron microscope to confirm the fracture was flexural. Data were
      analyzed by using 1-way analysis of variance test. RESULTS: R-Endo R3 instruments
      showed better cyclic fatigue resistance than ProTaper D3 and Mtwo R 25.05
      instruments, and the difference was statistically significant (P < .05). There
      was no significant difference between ProTaper D3 and Mtwo R 25.05 groups.
      CONCLUSIONS: The R-Endo R3 instruments were more resistant to fatigue failure
      than ProTaper D3 and Mtwo R 25.05.

PMID- 22152633
TI  - Chemical interaction of alexidine and sodium hypochlorite.
AB  - INTRODUCTION: Recent studies have reported the color change and formation of
      precipitates containing para-chloroaniline (PCA) after a reaction of sodium
      hypochlorite (NaOCl) and chlorhexidine (CHX). Alexidine (ALX), a biguanide
      disinfectant similar to CHX, has greater affinity for bacterial virulence factors
      than CHX. This study determined by electrospray ionization mass spectrometry (ESI
      MS) and scanning electron microscopy (SEM) whether the chemical interaction
      between ALX and NaOCl results in PCA or precipitates. METHODS: ESI-MS was
      performed on 4 different concentrations of ALX (1%, 0.5%, 0.25%, and 0.125%) with
      4% NaOCl to detect the presence of PCA. As control groups, 1% ALX, 0.5% PCA, and
      a mixture of 2% CHX and 4% NaOCl were analyzed. The formation of precipitates on
      the dentinal surfaces of premolar root canals treated with the solutions of ALX
      and NaOCl (AN) or CHX and NaOCl (CN) was observed by SEM and the color change in
      the reaction solutions was also analyzed. RESULTS: ESI-MS showed that the peak
      (mass/charge ratio = 128.026) in the PCA spectrum was not detected in any of the
      4 AN solutions, whereas the peak was found in the CN solution. SEM revealed
      precipitates covering dentinal surfaces in the CN solution. The AN solutions
      produced no precipitate. The AN solutions changed in color from light yellow to
      transparent with decreasing ALX concentration, whereas peach-brown discoloration
      was observed in the CN solution. CONCLUSIONS: The interaction of ALX and NaOCl
      did not produce PCA or precipitates, and the color of the reacted solution
      changed transparent with decreasing ALX concentration.

PMID- 22152634
TI  - Comparison among manual instruments and PathFile and Mtwo rotary instruments to
      create a glide path in the root canal preparation of curved canals.
AB  - INTRODUCTION: Nickel-titanium rotary instruments reduce procedural errors and the
      time required to finish root canal preparation. The goal of this study was to
      evaluate the occurrences of apical transportation and canal aberrations produced
      with different instruments used to create a glide path in the preparation of
      curved root canals, namely manual K-files (Dentsply Maillefer, Ballaigues,
      Switzerland) and PathFile (Dentsply Maillefer) and Mtwo (Sweden and Martina,
      Padua, Italy) nickel-titanium rotary files. METHODS: The mesial canals of 45
      mandibular first and second molars (with curvature angles between 25 degrees  and
      35 degrees ) were selected for this study. The specimens were divided randomly
      into 3 groups with 15 canals each, and canal preparation was performed by an
      endodontist using #10-15-20 K-type stainless steel manual files (group M), #13-16
      19 PathFile rotary instruments (group PF), and #10-15-20 Mtwo rotary instruments
      (group MT). The double digital radiograph technique was used, pre- and
      postinstrumentation, to assess whether apical transportation and/or aberration in
      root canal morphology occurred. The initial and final images of the central axis
      of the canals were compared by superimposition through computerized analysis and
      with the aid of magnification. The specimens were analyzed by 3 evaluators, whose
      calibration was checked using the Kendall agreement test. RESULTS: No apical
      transportation or aberration in root canal morphology occurred in any of the
      teeth; therefore, no statistical analysis was conducted. CONCLUSIONS: Neither the
      manual instruments nor the PathFile or Mtwo rotary instruments used to create a
      glide path had any influence on the occurrence of apical transportation or
      produced any canal aberration.

PMID- 22152635
TI  - Autotransplantation with simultaneous sinus floor elevation.
AB  - INTRODUCTION: Autotransplantation of the third molar is a viable option for
      replacing missing molars and has some benefits. This case report showed
      successful autotransplantation with simultaneous sinus floor elevation and
      implant installation. METHODS: The patient suffered a loss of maxillary molars
      and had a pneumatized maxillary sinus under the area in need of restorative
      treatment. Instead of implant installation in the molar area, we performed
      autotransplantation of the mandibular third molar with simultaneous sinus floor
      elevation with the aid of computer-aided rapid prototyping model. RESULTS:
      Healing was uneventful. There were no subsequent long-term symptoms or discomfort
      in the transplanted area. Clinical examinations revealed no mobility of the
      transplanted tooth, and there was no radiographic evidence of root resorption or
      ankylosis at a follow-up visit 4 years after transplantation. CONCLUSIONS:
      Autotransplantation with simultaneous sinus floor elevation is a potential
      treatment alternative to implant installation in selected cases.

PMID- 22152636
TI  - Magnetic resonance imaging for Meniere's disease: correlation with tone burst
      electrocochleography.
AB  - The newly developed use of magnetic resonance imaging of the human inner ear, on
      a 3 Tesla scanner with intratympanically administered gadolinium, can now
      reliably distinguish perilymph from endolymph and visually confirm the presence
      or absence of endolymphatic hydrops. Transtympanic tone burst
      electrocochleography is an established, and under-utilised evoked response
      electrophysiological test for hydrops, but it relies on a symptom score to
      indicate the likelihood of hydrops being present. The current diagnostic criteria
      for Meniere's disease make no allowance for any in vivo test, making diagnostic
      errors likely. In this small pilot study of three patients undergoing tone burst
      electrocochleography, subsequent magnetic resonance imaging confirmed or excluded
      the hydrops that the electrocochleography predicted. Magnetic resonance imaging
      of the inner ear is a safe technique that can be performed in conjunction with
      imaging of the VIIIth cranial nerves. As this report comprised only three
      patients in a pilot study, rigorous clinical studies are required to define the
      possible role of magnetic resonance imaging in the diagnosis of Meniere's
      disease.

PMID- 22152637
TI  - Determinants of vitamin D status in young children: results from the Belgian arm
      of the IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced
      Health Effects in Children and Infants) Study.
AB  - OBJECTIVE: To describe the vitamin D status of Belgian children and examine the
      influence of non-nutritional determinants, in particular of anthropometric
      variables. DESIGN: Cross-sectional data of Belgian participants of the EU 6th
      Framework Programme IDEFICS (Identification and Prevention of Dietary- and
      Lifestyle-Induced Health Effects in Children and Infants) Study. SETTING: 25
      Hydroxyvitamin D (25(OH)D) was measured using RIA. Vitamin D status was
      categorized as deficient (<25 nmol/l), insufficient (25-50 nmol/l), sufficient
      (50-75 nmol/l) and optimal (>=75 nmol/l). Anthropometric measurements included
      height, weight, waist and hip circumferences and triceps and subscapular skinfold
      thicknesses. SUBJECTS: Children (n 357) aged 4-11 years. RESULTS: Serum 25(OH)D
      ranged from 13.6 to 123.5 nmol/l (mean 47.2 (sd 14.6) nmol/l); with 5 %
      deficient, 53 % insufficient, 40 % sufficient and 2 % optimal. No significant
      differences were found by age and gender. Significant differences in 25(OH)D were
      observed for month of sampling (P < 0.001), number of hours playing outside per
      week (r = 0.140), weight (r = -0.121), triceps (r = -0.112) and subscapular (r = 
      0.119) skinfold thickness, sum of two skinfold thicknesses (r = -0.125) and waist
      circumference (r = -0.108). Linear regression analysis of 25(OH)D adjusted for
      age, month of sampling and hours playing outside per week suggested that (i)
      weight, (ii) BMI Z-score, (iii) waist circumference and (iv) triceps and
      subscapular skinfold thickness (as well as the sum of both) independently
      influenced 25(OH)D. CONCLUSIONS: The majority of Belgian children had a
      suboptimal vitamin D status, with more than half having an insufficient status in
      winter and spring. Month of the year, weekly number of hours playing outside and
      body composition - both central and abdominal obesity - were identified as
      important determinants of vitamin D status in Belgian children.

PMID- 22152638
TI  - Why has natural selection left us so vulnerable to anxiety and mood disorders?

PMID- 22152639
TI  - Anxiety: an evolutionary approach.
AB  - Anxiety disorders are among the most common mental illnesses, with huge attendant
      suffering. Current treatments are not universally effective, suggesting that a
      deeper understanding of the causes of anxiety is needed. To understand anxiety
      disorders better, it is first necessary to understand the normal anxiety
      response. This entails considering its evolutionary function as well as the
      mechanisms underlying it. We argue that the function of the human anxiety
      response, and homologues in other species, is to prepare the individual to detect
      and deal with threats. We use a signal detection framework to show that the
      threshold for expressing the anxiety response ought to vary with the probability
      of threats occurring, and the individual's vulnerability to them if they do
      occur. These predictions are consistent with major patterns in the epidemiology
      of anxiety. Implications for research and treatment are discussed.

PMID- 22152640
TI  - Evolutionary theories of depression: a critical review.
AB  - We critically review evolutionary theories of major depressive disorder (MDD).
      Because most instances of MDD appear to be caused by adversity, evolutionary
      theories of MDD generally propose that sadness and low mood evolved as beneficial
      responses to adversity, and that MDD is dysfunctional sadness and low mood. If
      so, MDD research should focus much more heavily on understanding the healthy
      functions of sadness and low mood to better understand how they dysfunction. A
      debate about the boundary between healthy sadness and MDD is then reviewed. In
      part, this debate turns on whether MDD's costliest symptoms could provide unknown
      benefits. Therefore, the review concludes by discussing 2 theories that explore
      possible benefits of prolonged anhedonia and suicidality.

PMID- 22152641
TI  - Autism spectrum disorders and maternal serum alpha-fetoprotein levels during
      pregnancy.
AB  - OBJECTIVE: Numerous studies have been trying to disentangle the complex
      pathophysiology of autism spectrum disorders (ASD). In our study, we explored the
      potential role of maternal serum (MS) alpha-fetoprotein (AFP) in the prediction
      and the pathophysiology of ASD. METHODS: A total of 112 patients with ASD and 243
      control subjects were included in a case-control study, using a historic birth
      cohort maintained at Statens Serum Institute. Measurements of MS-AFP were
      obtained from a multicentre screening program, whereas clinical data were
      obtained from nationwide registers. Association between MS-AFP and ASD status was
      analyzed using logistic regression models and nonparametric tests. RESULTS:
      Crude, but not adjusted, estimates showed that MS-AFP levels were slightly, but
      significantly, higher in mothers of children with ASD, compared with their
      control subject counterparts. People with ASD had an odds ratio of 2.33, with 95%
      confidence intervals of 1.00 to 5.39, to have MS-AFP above 2.5 multiple of
      median. Excluding subjects with congenital malformation comorbidities did not
      alter the direction of our estimates (OR 2.60; 95% CI 1.04 to 6.51, P = 0.04).
      CONCLUSION: Biologic plausibility of its role in the pathophysiology of ASD makes
      AFP a good candidate for further larger-scale studies to confirm such an
      association and to determine whether this pattern is unique to ASD or related to
      other psychiatric disorders as well.

PMID- 22152642
TI  - Enculturation and alcohol use problems among aboriginal university students.
AB  - OBJECTIVE: To examine associations between aboriginal enculturation, Canadian
      acculturation, and alcohol problems among aboriginal university students living
      in an urban area in Canada. METHODS: Data for this mixed methods study were
      collected through in-person surveys with a convenience sample of aboriginal
      university students (n = 60) in 2008/2009. RESULTS: Students evidenced high
      levels of aboriginal enculturation and Canadian acculturation. aboriginal
      enculturation was significantly associated with reduced alcohol problems for
      aboriginal university students. There was no association between Canadian
      acculturation and alcohol problems. Qualitative findings suggest aboriginal
      cultural practices helped students cope with problems in their daily lives and
      provided them with both personal and social rewards. CONCLUSIONS: This study
      found aboriginal enculturation was significantly associated with reduced alcohol
      problems among aboriginal university students. Results support the growth of
      programs and services that encourage aboriginal students to maintain their
      cultural identity within the university setting.

PMID- 22152643
TI  - The association of treatment of depressive episodes and work productivity.
AB  - OBJECTIVE: About one-third of the annual $51 billion cost of mental illnesses is
      related to productivity losses. However, few studies have examined the
      association of treatment and productivity. The purpose of our research is to
      examine the association of depression and its treatment and work productivity.
      METHODS: Our analyses used data from 2737 adults aged between 18 and 65 years who
      participated in a large-scale community survey of employed and recently employed
      people in Alberta. Using the World Health Organization's Health and Work
      Performance Questionnaire, a productivity variable was created to capture high
      productivity (above the 75th percentile). We used regression methods to examine
      the association of mental disorders and their treatment and productivity,
      controlling for demographic factors and job characteristics. RESULTS: In the
      sample, about 8.5% experienced a depressive episode in the past year. The
      regression results indicated that people who had a severe depressive episode were
      significantly less likely to be highly productive. Compared with people who had a
      moderate or severe depressive episode who did not have treatment, those who did
      have treatment were significantly more likely to be highly productive. However,
      about one-half of workers with a moderate or severe depressive episode did not
      receive treatment. CONCLUSIONS: Our results corroborate those in the literature
      that indicate mental disorders are significantly associated with decreased work
      productivity. In addition, these findings indicate that treatment for these
      disorders is significantly associated with productivity. Our results also
      highlight the low proportion of workers with a mental disorder who receive
      treatment.

PMID- 22152644
TI  - Effectively working on rehabilitation goals: 24-month outcome of a randomized
      controlled trial of the Boston psychiatric rehabilitation approach.
AB  - OBJECTIVE: To investigate the effect of the Boston Psychiatric Rehabilitation
      (PR) Approach on attainment of personal rehabilitation goals, social functioning,
      empowerment, needs for care, and quality of life in people with severe mental
      illness (SMI) in the Netherlands. METHOD: A 24-month, multicentre, randomized
      controlled trial was used to compare the results of PR to care as usual (CAU).
      Patients with SMI were randomly assigned by a central randomization centre to PR
      (n = 80) or CAU (n = 76). The primary outcome of goal attainment was assessed by
      independent raters blind to treatment allocation. Measures for secondary outcomes
      were change in work situation and independent living, the Personal Empowerment
      Scale, the Camberwell Assessment of Needs, and the World Health Organization
      Quality of Life assessment. Effects were tested at 12 and 24 months. Data were
      analyzed according to intention to treat. Covariates were psychiatric centre,
      psychopathology, number of care contacts, and educational level of the
      professionals involved. RESULTS: The rate of goal attainment was substantially
      higher in PR at 24 months (adjusted risk difference: 21%, 95% CI 4% to 38%;
      number needed to treat [NNT] = 5). The approach was also more effective in the
      area of societal participation (PR: 21% adjusted increase, CAU: 0% adjusted
      increase; NNT = 5) but not in the other secondary outcome measures. CONCLUSIONS:
      The results suggest that PR is effective in supporting patients with SMI to reach
      self-formulated rehabilitation goals and in enhancing societal participation,
      although no effects were found on the measures of functioning, need for care, and
      quality of life.

PMID- 22152645
TI  - Perception of teratogenic risk and the rated likelihood of pregnancy termination:
      association with maternal depression.
AB  - OBJECTIVE: Women are often exposed to various medications and medical conditions
      during pregnancy. Unrealistically high maternal teratogenic risk perception,
      related to these exposures, may lead to abrupt discontinuation of therapy and
      (or) termination of a wanted pregnancy. The association between maternal
      depression and the teratogenic risk perception has not been studied, nor were the
      actions resulting from this perception. Our objectives were to explore the
      association between maternal depression, teratogenic risk perception, and the
      rated likelihood to terminate pregnancy. Additionally, we evaluated possible
      benefits of counselling. METHODS: We administered the Edinburgh Postnatal
      Depression Scale (EPDS) to all women who attended the Motherisk Clinic between
      October 2007 and April 2010. A visual analogue scale was used to determine
      maternal risk perception in relation to the specific exposure, and the rated
      likelihood to terminate the pregnancy, before and after counselling. RESULTS: We
      analyzed data from 413 women. Maternal teratogenic risk perception and the rated
      likelihood to terminate the pregnancy were significantly lower following
      counselling. An EPDS score of 13 or more was significantly associated with a
      higher rated likelihood to terminate the pregnancy (P = 0.03). In a multivariable
      regression analysis, an EPDS score of 13 or more was found to be an independent
      predictor of a higher personal teratogenic risk perception (P = 0.03).
      CONCLUSIONS: Both maternal depression and exposure-directed counselling are
      associated with maternal risk perception and the rated likelihood to terminate
      pregnancy. Appropriate counselling may reduce fear of teratogenicity and the
      likelihood of pregnancy termination.

PMID- 22152646
TI  - High-dose supplemental selenite to male Syrian hamsters fed hypercholesterolaemic
      diets alters Ldlr, Abcg8 and Npc1l1 mRNA expression and lowers plasma cholesterol
      concentrations.
AB  - The aim of the present study was to elucidate possible cholesterol-lowering
      mechanism(s) of high-dose supplemental Se in the form of selenite, a known
      hypocholesterolaemic agent. Male Syrian hamsters (four groups, ten per group)
      were fed semi-purified diets for 4 weeks containing 0.1 % cholesterol and 15 %
      saturated fat with selenite corresponding to varying levels of Se: (1) Se 0.15
      parts per million (ppm), control diet; (2) Se 0.85 ppm; (3) Se 1.7 ppm; (4) Se
      3.4 ppm. Lipids were measured in the bile, faeces, liver and plasma. The mRNA
      expression of several known regulators of cholesterol homeostasis (ATP-binding
      cassette transporters g5 (Abcg5) and g8 (Abcg8), 7-hydroxylase, 3-hydroxy-3
      methylglutaryl-coenzyme A reductase, LDL receptor (LdLr) and Nieman-Pick C1-like
      1 protein (Npc1l1)) were measured in the liver and/or jejunum. Oxysterols
      including 24-(S)-hydroxycholesterol, 25-hydroxycholesterol and 27
      hydroxycholesterol (27-OHC) were measured in the liver. Significantly lower total
      plasma cholesterol concentrations were observed in hamsters consuming the low
      (0.85 ppm) and high (3.4 ppm) Se doses. The two highest doses of Se resulted in
      decreased plasma LDL-cholesterol concentrations and increased mRNA levels of
      hepatic Abcg8, Ldlr and jejunal Ldlr. Higher hepatic 27-OHC and TAG
      concentrations and lower levels of jejunal Npc1l1 mRNA expression were noted in
      the 1.7 and 3.4 ppm Se-treated hamsters. Overall, Se-induced tissue changes in
      mRNA expression including increased hepatic Abcg8 and Ldlr, increased jejunal
      Ldlr and decreased jejunal Npc1l1, provide further elucidation regarding the
      hypocholesterolaemic mechanisms of action of Se in the form of selenite.

PMID- 22152647
TI  - Long-term effect of gamma irradiation on the functional properties and
      cytocompatibility of multiblock co-polymer films.
AB  - The purpose of this work was to investigate the long-term effect of gamma
      irradiation treatment on the functional properties of PEG-PDLLA and PEG-PLGA
      films and to evaluate the cytocompatibility of sterilized samples. Chemical and
      thermal properties, and cytocompatibility of sterilized films were detected for
      samples at time zero and after storage at 5 +/- 3 degrees C for 60 days. An in
      vitro degradation study was carried out on polymer samples to examine the effect
      of sterilization on the degradation performances of co-polymer films. Incubated
      samples were characterized in terms of film surface structure (SEM), chemical
      (GPC) and thermal (DSC) properties. The study performed on films upon gamma
      sterilization showed no significant changes of the PEG-PDLLA and PEG-PLGA film
      structure, while GPC analysis highlighted that the effect of gamma irradiation
      was dependent on the Mw and composition of polymers. DSC traces suggested more
      pronounced gamma-ray effects on the PEG-PLGA multiblock co-polymer. During the
      stability study important changes in terms of structure surface, thermal
      properties and cytocompatibility were observed and investigated. Data collected
      during the in vitro degradation study emphasized the need to know and investigate
      the degradation performances and behaviour of polymer or polymer systems (as DDS,
      scaffolds and bandage) treated with gamma rays. 

PMID- 22152648
TI  - Dengue: a newly emerging viral infection in Andaman and Nicobar Islands, India.
AB  - Prior to 2009 dengue fever had not been reported in the Andaman and Nicobar
      archipelago. In 2009, a few patients with dengue fever-like illness were
      reported, some of whom tested positive for dengue antibodies. In 2010, 516
      suspected cases were reported, including some with dengue haemorrhagic fever
      (DHF) and dengue shock syndrome (DSS); 80 (15.5%) were positive for dengue
      antibodies. DENV RNA was detected in five patients and PCR-based typing showed
      that three of these belonged to serotype 1 and two to serotype 2. This was
      confirmed by sequence typing. Two clones of dengue virus, one belonging to
      serotype 1 and the other to serotype 2 appeared to be circulating in Andaman.
      Emergence of severe diseases such as DHF and DSS might be due to recent
      introduction of a more virulent strain or because of the enhancing effect of sub
      neutralizing levels of antibodies developed due to prior infections. There is a
      need to revise the vector-borne disease surveillance system in the islands.

PMID- 22152649
TI  - Change of energy expenditure from physical activity is the most powerful
      determinant of improved insulin sensitivity in overweight patients with coronary
      artery disease participating in an intensive lifestyle modification program.
AB  - The objective was to evaluate the determinants of change (Delta) in insulin
      sensitivity in overweight coronary artery disease male patients without diabetes
      after an intensive lifestyle intervention. All patients received nutritional
      counseling and performed 4 months of exercise training (ET) according to 1 of 2
      protocols: aerobic ET (65%-70% of peak aerobic capacity [VO(2)]) 25 to 40 minutes
      3 times a week (n = 30) or walking (50%-60% of peak VO(2)) 45 to 60 minutes at
      least 5 times a week (n = 30). Data from participants of both ET groups were
      pooled, and post-intensive lifestyle intervention results were compared with
      baseline data. The primary outcome was Delta insulin sensitivity (m-value)
      assessed by the criterion standard technique, the euglycemic-hyperinsulinemic
      clamp. Changes in weight, body mass index, total and percentage fat mass (by dual
      energy x-ray absorptiometry scan), waist circumference, total abdominal and
      visceral fat (by computed tomographic scan), high-sensitivity C-reactive protein,
      peak VO(2), daily energy intake, and physical activity energy expenditure (PAEE)
      (by doubly labeled water technique) were also assessed. Daily energy intake
      decreased by 335 kcal, and PAEE increased by 482 kcal/d (all P < .0001). The mean
      weight loss was 6.4 kg, and the mean improvement in m-value was 1.6 mg/kg fat
      free mass per minute. Univariate determinants of Delta m-value were low baseline
      PAEE, walking protocol, Delta weight, Delta body mass index, Delta total and
      percentage fat mass, Delta waist circumference, Delta total abdominal and
      visceral fat, and Delta PAEE (all P < .05). In multivariate analysis, the only
      significant determinant of Delta m-value was Delta PAEE (P < .02). In this
      analysis, the most powerful determinant of improved insulin sensitivity in
      overweight coronary artery disease patients is the change in PAEE.

PMID- 22152651
TI  - [Cross-cultural adaptation and validation of the Dizziness Handicap Inventory:
      Argentine version].
AB  - INTRODUCTION AND OBJECTIVES: The Dizziness Handicap Inventory is a useful tool
      for quantifying self-perceived handicap in patients with vertigo, dizziness or
      unsteadiness and its impact on daily living activities. The Dizziness Handicap
      Inventory identifies functional, physical and emotional disorders related to
      balance disturbance. Our objective was to cross-culturally adapt the Peninsular
      Spanish version of the Dizziness Handicap Inventory for use in Argentina and
      validate the adapted Argentinian version. METHODS: We included both healthy
      subjects and patients with vertigo, dizziness or unsteadiness, aged 18 to 85
      years, native Spanish-speaking Argentinians. We introduced linguistic and
      cultural modifications to the Peninsular Spanish version to obtain the
      Argentinian one. This version was given twice to 108 patients, 24 to 72 h apart.
      Internal consistency, test-retest reliability and construct validity were
      assessed using a visual analogue scale, the Romberg test, the tandem Romberg test
      and the tandem gait test. RESULTS: We found high internal consistency
      (alpha=0.87) and very high test-retest reliability for the total Dizziness
      Handicap Inventory score (intraclass correlation coefficient: 0.98) and its
      subscales. The total Dizziness Handicap Inventory and the functional subscale
      were found to correlate significantly with the Romberg and tandem Romberg tests.
      The emotional subscale showed a significant correlation with the Romberg test and
      the eyes-open tandem Romberg test (P<.05) CONCLUSIONS: The Argentinian version of
      the Dizziness Handicap Inventory proved to be a reliable and valid tool to
      quantify self-perceived handicap resulting from vertigo, dizziness or
      unsteadiness.

PMID- 22152652
TI  - [Tinnitus measurement with conventional audiometer versus high-frequency
      audiometer].
AB  - INTRODUCTION AND OBJECTIVES: Determinations of the psychoacoustic characteristics
      of tinnitus (frequency and intensity) are valid for diagnosis, treatment,
      monitoring and research purposes. The aim of this work is to compare the
      frequency of the tinnitus measured with a standard audiometer and a high
      frequency audiometer. METHODS: We used a conventional audiometer (frequency
      range: 125-12,000 Hz) and a high-frequency audiometer (frequency range: 125
      18,000 Hz) to measure the frequency and intensity of tinnitus in 47 patients with
      tinnitus as a continuous ringing. RESULTS: We found statistically-significant
      differences between the determination of the frequency of tinnitus made with
      conventional and high-frequency audiometers, as well as a correlation between
      high-frequency tinnitus and distress expressed by patients. CONCLUSIONS: 1) The
      frequency of tinnitus determined by high-frequency audiometer is greater than the
      frequency determined by conventional audiometer; 2) the higher the frequency of
      tinnitus, the more discomfort the patient manifests; and 3) there is no
      relationship between the intensity and discomfort caused by tinnitus.

PMID- 22152650
TI  - Effects of high-fructose corn syrup and sucrose on the pharmacokinetics of
      fructose and acute metabolic and hemodynamic responses in healthy subjects.
AB  - It is unclear whether high-fructose corn syrup (HFCS), which contains a higher
      amount of fructose and provides an immediate source of free fructose, induces
      greater systemic concentrations of fructose as compared with sucrose. It is also
      unclear whether exposure to higher levels of fructose leads to increased fructose
      induced adverse effects. The objective was to prospectively compare the effects
      of HFCS- vs sucrose-sweetened soft drinks on acute metabolic and hemodynamic
      effects. Forty men and women consumed 24 oz of HFCS- or sucrose-sweetened
      beverages in a randomized crossover design study. Blood and urine samples were
      collected over 6 hours. Blood pressure, heart rate, fructose, and a variety of
      other metabolic biomarkers were measured. Fructose area under the curve and
      maximum concentration, dose-normalized glucose area under the curve and maximum
      concentration, relative bioavailability of glucose, changes in postprandial
      concentrations of serum uric acid, and systolic blood pressure maximum levels
      were higher when HFCS-sweetened beverages were consumed as compared with sucrose
      sweetened beverages. Compared with sucrose, HFCS leads to greater fructose
      systemic exposure and significantly different acute metabolic effects.

PMID- 22152654
TI  - Editor's corner: the family is changing.

PMID- 22152653
TI  - [Sound therapy in sudden deafness].
AB  - INTRODUCTION AND GOALS: Idiopathic sudden sensorineural hearing loss is a hearing
      disorder of unknown cause. The spontaneous recovery rate ranges from 50 to 75% of
      the patients. Scientific experiments on animals support the present study in
      patients with sudden deafness treated with sounds. PATIENTS AND METHODS: During
      the period 2003-2009, patients with idiopathic sudden sensorineural hearing loss
      were administered steroids, piracetam and antioxidants, together with the
      addition of sounds by means of music and words. RESULTS: Comparing the results of
      patients treated with medication (n=65) and those treated with medication and
      sounds (n=67), it was observed that patients treated with medication and sounds
      had higher recovery. Within the group of patients treated with medication and
      sounds, 25 (37%) experienced complete recovery, 28 (42%) good recovery, 11 (16%)
      slight recovery and 3 (5%) poor or no recovery. CONCLUSION: The patients who
      recovered more than half of their audition accounted for 54% in the group treated
      with medication and for 79% in the group of patients receiving medication and
      sounds. Auditory recuperation showed no alterations, at least up to 12 months
      after therapy.

PMID- 22152655
TI  - The history of our field: reflections on the solid foundations on which we stand-
      the contributions of Griffith Edwards.

PMID- 22152656
TI  - Substance use disorders and homicide death in veterans.
AB  - OBJECTIVE: The present study examined the association between a diagnosis of an
      alcohol use disorder or a drug use disorder and death by homicide over the course
      of 6 years. METHOD: This was a cohort study that included all patients seen for
      medical treatment by the Veterans Health Administration during fiscal year (FY)
      2001. Treatment records were used to identify all patients with a diagnosis of a
      substance use disorder in FY01 (n = 3,942,932). The National Death Index data
      provided information on the timing and cause of death between FY02 and the end of
      2007. Analyses examined the association between substance use disorders and the
      time to homicide, after controlling for age and gender. RESULTS: Veterans Health
      Administration patients who were diagnosed with an alcohol use disorder were more
      likely to die by homicide than those without a substance use disorder (hazard
      ratio [HR] = 3.3, 95% CI [2.6,4.1]). This finding also was true for those with
      drug use disorders (HR = 4.3, 95% CI [3.4, 5.4]) and for those with both an
      alcohol use disorder and a drug use disorder (HR = 4.6, 95% CI [3.9, 5.4]),
      compared with those without a substance use disorder. CONCLUSIONS: In this
      observational study of veterans, a diagnosis of a substance use disorder was
      significantly associated with death by homicide. Alcohol and drug treatment
      programs may have an important role to play in reducing the burden of homicide as
      a public health problem.

PMID- 22152657
TI  - Case-control study in China of risk factors for suicide in men with alcohol use
      disorders.
AB  - OBJECTIVE: This secondary analysis of China's National Psychological Autopsy
      Study assesses the risk factors for suicide among men with alcohol use disorders
      (AUDs)--the second most common psychiatric diagnosis among suicide decedents in
      China. METHOD: Based on data collected from family members and close associates,
      the characteristics of 68 men with AUDs who died by suicide and 51 men with AUDs
      who died of other injuries at 23 geographically representative locations in China
      were compared using univariate and multivariate logistic regression models.
      Interactions between AUDs and other risk factors for suicide were explored using
      data from 448 male suicide decedents and 521 men who died from accidental
      injuries. RESULTS: After adjusting for covariates, risk factors for suicide among
      men with AUDs were history of previous suicide attempts (odds ratio [OR] = 46.72,
      95% CI [4.70, 464.89]), acute negative life events in the 2 days before death (OR
      = 18.92, 95% CI [3.32, 107.88]), and comorbid major depressive disorder (OR =
      14.65, 95% CI [2.93, 73.31]). These three factors accounted for 54.3% of the
      variance in outcome. There was a statistically significant interaction between
      AUDs and major depression; the association between major depression and suicide
      risk was weaker in men with AUDs than in men without AUDs. CONCLUSIONS: Among men
      with AUDs in China, prior suicidal behavior, acute life events, and major
      depression confer risk for suicide. However, the risk associated with depression
      in men with AUDs is somewhat less than the risk of suicide associated with
      depression in men without AUDs.

PMID- 22152658
TI  - Is the density of alcohol establishments related to nonviolent crime?
AB  - OBJECTIVE: We examined the associations between the density of alcohol
      establishments and five types of nonviolent crime across urban neighborhoods.
      METHOD: Data from the city of Minneapolis, MN, in 2009 were aggregated and
      analyzed at the neighborhood level. We examined the association between alcohol
      establishment density and five categories of nonviolent crime: vandalism,
      nuisance crime, public alcohol consumption, driving while intoxicated, and
      underage alcohol possession/consumption. A Bayesian approach was used for model
      estimation accounting for spatial auto-correlation and controlling for relevant
      neighborhood demographics. Models were estimated for total alcohol establishment
      density and then separately for off-premise establishments (e.g., liquor and
      convenience stores) and on-premise establishments (e.g., bars and restaurants).
      RESULTS: We found positive associations between density and each crime category.
      The association was strongest for public consumption and weakest for vandalism.
      We estimated that a 3.3%-10.9% increase across crime categories would result from
      a 20% increase in neighborhood establishment density. Similar results were seen
      for on- and off-premise establishments, although the strength of the associations
      was lower for off-premise density. CONCLUSIONS: Our results indicate that
      communities should consider the potential increase in nonviolent crime associated
      with an increase in the number of alcohol establishments within neighborhoods.

PMID- 22152659
TI  - Naturally occurring changes in women's drinking from high school to college and
      implications for sexual victimization.
AB  - OBJECTIVE: The current study examined the natural trajectories of alcohol use
      among women as they transitioned from high school to college, considering changes
      in drinking for students at initially different levels of drinking. We examined
      the hypothesis that the association between college drinking and sexual
      victimization would be stronger for women with less high school drinking
      experience. METHOD: Female, college-bound, high school seniors were recruited
      from the community at the time of graduation (N = 437). Alcohol consumption and
      sexual victimization were assessed at the time of high school graduation (Time 0
      [T0]) and at the end of the first (T1) and second (T2) semesters of college.
      RESULTS: Abstainers and light drinkers increased alcohol consumption from T0 to
      T1; however, consumption by those already engaging in heavy episodic drinking
      remained stable. Consumption did not increase for any group from T1 to T2. As
      expected, maximum consumption in college was strongly associated with
      experiencing incapacitated rape or other sexual victimization during the same
      semester; however, prior drinking experience did not moderate the relationship.
      CONCLUSIONS: Occasions of heavy drinking in college are a significant risk factor
      for sexual victimization for both experienced and inexperienced drinkers.
      Findings point toward universal prevention, ideally before college entry, as a
      strategy for reducing heavy episodic drinking and hence, college sexual
      victimization.

PMID- 22152660
TI  - Alcohol milestones, risk factors, and religion/spirituality in young adult women.
AB  - OBJECTIVE: The alcoholism research literature has long reported a significant,
      reliable, and inverse association between alcohol use disorders and
      religion/spirituality (R/S), and this is also evident in the period of highest
      risk--adolescence and young adulthood. In the treatment area, both clinical and
      mutual-help programs for alcohol use disorders often include a spiritual
      component, and outcome studies validate the efficacy of such programs. Even so,
      the alcoholism-R/S relationship is little understood. METHOD: The current study
      examined data from an existing sample of 4,002 female adolescents/young adults
      and their families. Data analyses examined five demographic, nine R/S, and eight
      risk-factor variables as predictors of five alcohol milestones: initial drink,
      first intoxication, regular use, heavy consumption, and alcohol dependence.
      RESULTS: Results affirmed the known association between alcoholism risk factors
      and alcohol use milestones and also found moderate to strong associations between
      most R/S variables and these risk factors and milestones. A multivariate model
      simultaneously examining both sets of variables found that specific risk factors
      and specific R/S variables remained significant predictors of alcohol use
      milestones after accounting for all other variables. Mediation and moderation
      tests did not find evidence that R/S accounted for or qualified the relationship
      between alcohol risk factors and alcohol milestones. CONCLUSIONS: This study
      confirmed the multidimensional role of R/S influences within the etiological
      network of alcoholism risk and protective factors in adolescents/young adults and
      found R/S dimensions to be independent and substantial influences on alcohol use
      disorders rather than mediators or moderators of other risks.

PMID- 22152661
TI  - Gender and extroversion as moderators of the association between Alcoholics
      Anonymous and sobriety.
AB  - OBJECTIVE: Although women make up one third of Alcoholics Anonymous (AA)
      membership, research on gender and AA has been limited. Findings in the
      literature are mixed, with few empirical investigations of factors that may
      moderate any gender differences found. AA is highly interpersonal, and research
      has found that women are more extroverted than men. The current study explores
      the impact of AA on sobriety, gender differences in the relationship between AA
      and sobriety, and whether extroversion can inform our understanding of gender
      differences. METHOD: A sample of 276 alcohol-dependent adults (180 men, 96 women)
      was recruited from four sites and followed prospectively for 2.5-3 years.
      Participants completed the Timeline Followback interview. AA membership was
      assessed by an item from the Alcoholics Anonymous Involvement scale. Multiple
      logistic regression analyses were conducted to determine whether gender,
      extroversion, AA membership, and their interaction would predict sobriety status
      at follow-up. RESULTS: AA membership significantly increased the odds of
      achieving a year of sobriety, and this relationship was stronger for women than
      men (odds ratio [OR] = 4.42, 95% CI [1.14, 17.18]). There were no main or
      interactive effects of extroversion on sobriety. CONCLUSIONS: A A was founded by
      men, and early in its history it was exclusively attended by men. Some have
      criticized AA for women because of its emphasis on "powerlessness." Despite its
      historical beginnings and such debate, this study joins others in finding
      evidence that women fare better in AA than do men. In this sample, extroversion
      did not moderate the association between gender and sobriety. Further research is
      needed on gender differences in AA and its explanatory factors.

PMID- 22152662
TI  - Increases in typical quantities consumed and alcohol-related problems during a
      decade of liberalizing alcohol policy.
AB  - OBJECTIVE: The aim of this study was to assess trends in drinking patterns and
      alcohol-related problems among age and gender groups in the context of a
      liberalized alcohol policy environment. METHOD: Eleven comparable general
      population alcohol surveys were conducted between 1990 and 2000 in Auckland, New
      Zealand, during which a substantial number of liberalizing alcohol policy changes
      occurred. Measurements included typical-occasion quantity and frequency of
      drinking in the last 12 months. Self-reported alcohol-related problems in the
      last 12 months were divided into two groups based on risk curve analysis:
      threshold problems (experienced only once a high level of consumption is reached)
      and nonthreshold problems (those exhibiting a dose-response relationship). Age
      groups were 14-19, 20-24, 25-39, and 40-65 years. RESULTS: Significant increases
      in typical-occasion quantity were found for young men and young women ages 14-19
      years and for women 20-24 and 40-65 years. The increase was most marked among
      those 14-19 years old. Only women ages 25-39 years increased how often they
      drank. The prevalence of threshold problems significantly increased among male
      drinkers ages 14-19 and 40-65 years. The proportion of 14- to 19-year-olds
      experiencing threshold problems was observed to be higher in each year compared
      with those 40-65 years old, and the 14- to 19-year-olds experienced a greater
      year-on-year increase. Increases in nonthreshold alcohol-related problems
      occurred for the youngest and oldest males and for most female age groups (14-19,
      25-39, and 40-65 years). The increase was most marked among those 14-19 years
      old. CONCLUSIONS: Increases in quantities consumed and alcohol-related problems
      were found predominantly among young people and women. The youngest age group,
      those 14-19 years old, experienced the most marked increases in quantity consumed
      and problems including, for males, the experience of more serious problems such
      as "had hands shake in the morning" (experienced only once a high level of
      consumption is reached).

PMID- 22152663
TI  - Intergenerational relations for drinking motives: invariant for same- and
      opposite-sex parent-child dyads?
AB  - OBJECTIVE: The purpose of this study was to investigate the similarity or
      dissimilarity of same-sex (e.g., mother-daughter) and opposite-sex (e.g., mother
      son) associations for drinking motives across four pairings of parent-young adult
      child dyads. METHOD: Three waves of data spanning approximately 10 years in early
      to late young adulthood were used in conjunction with mother and father data to
      examine same-and cross-sex associations for drinking motives. Multiple group
      structural equation modeling was used to statistically model and evaluate these
      parent-young adult associations. RESULTS: Findings indicated strong same-sex
      intergenerational transmission patterns for mother-daughter dyads relative to
      father-daughter dyads. The strength of relationships for father-son dyads was
      also stronger and significantly different than those for father-daughter dyads.
      There were no statistically significant differences between sex-specific
      intergenerational patterns for mother-son and father-son dyads or for mother
      daughter and mother-son dyads. Although there was some generality and some
      specificity in the sex-specific intergenerational transmission patterns of
      drinking motives, when statistically significant, the transmission pattern
      generalized across all three drinking motives (coping, social, and enhancement).
      CONCLUSIONS: Intergenerational factors contributing to alcohol phenotypes may not
      be limited to the modeling of alcohol use or the occurrence of alcohol disorders
      but may also include cognitive-motivational systems of affective regulation
      related to the use of alcohol. Future research would benefit by focusing on how
      biogenetic and socialization factors contribute to same- and opposite-sex
      intergenerational patterns and how to use this information to strengthen
      intervention programs.

PMID- 22152664
TI  - Investigating associations between perceived parental alcohol-related messages
      and college student drinking.
AB  - OBJECTIVE: A debate remains regarding whether parents should teach their children
      harm-reduction tips for using alcohol while in college or whether they should
      maintain a zero-tolerance policy. Which type of alcohol-related communication
      parents should endorse is not empirically clear. The current study made use of a
      longitudinal measurement-burst design to examine this issue. METHOD: The sample
      consisted of 585 second-year students from a large university in the northeastern
      United States. Participants completed a baseline survey and 14 daily web-based
      surveys. Students were assessed for perceptions of parental alcohol-related
      messages and their own alcohol use. Multilevel models were estimated using HLM
      6.04. RESULTS: The data indicate that zero-tolerance messages appeared most
      protective against alcohol use and consequences. Harm-reduction messages were
      most risky, even when compared with mixed messages or the absence of a message.
      CONCLUSIONS: Findings indicate that a zero-tolerance approach was associated with
      safer outcomes than other messages, even if students were already using alcohol.

PMID- 22152665
TI  - Wine consumption and 20-year mortality among late-life moderate drinkers.
AB  - OBJECTIVE: This study examined level of wine consumption and total mortality
      among 802 older adults ages 55-65 at baseline, controlling for key
      sociodemographic, behavioral, and health status factors. Despite a growing
      consensus that moderate alcohol consumption is associated with reduced total
      mortality, whether wine consumption provides an additional, unique protective
      effect is unresolved. METHOD: Participants were categorized in three subsamples:
      abstainers, high-wine-consumption moderate drinkers, and low-wine-consumption
      moderate drinkers. Alcohol consumption, sociodemographic factors, health
      behavior, and health problems were assessed at baseline; total mortality was
      indexed across an ensuing 20-year period. RESULTS: After adjusting for all
      covariates, both high-wine-consumption and low-wine-consumption moderate drinkers
      showed reduced mortality risks compared with abstainers. Further, compared with
      moderate drinkers for whom a high proportion of ethanol came from wine, those for
      whom a low proportion of ethanol came from wine were older, were more likely to
      be male, reported more health problems, were more likely to be tobacco smokers,
      scored lower on socioeconomic status, and (statistical trend) reported engaging
      in less physical activity. Controlling only for overall ethanol consumption,
      compared with moderate drinkers for whom a high proportion of ethanol came from
      wine, those for whom a low proportion of ethanol came from wine showed a
      substantially increased 20-year mortality risk of 85%. However, after controlling
      for all covariates, the initial mortality difference associated with wine
      consumption was no longer significant. CONCLUSIONS: Among older adults who are
      moderate drinkers, the apparent unique effects of wine on longevity may be
      explained by confounding factors correlated with wine consumption.

PMID- 22152666
TI  - Alcohol use and friendship dynamics: selection and socialization in early-,
      middle-, and late-adolescent peer networks.
AB  - OBJECTIVE: This study examined developmental trends of peer selection and
      socialization related to friends' alcohol use in early-, middle-, and late
      adolescent peer networks, with the primary goal of identifying when these
      mechanisms emerge, when these mechanisms exert their strongest effects, and when
      (or if) they decrease in importance. Gender and reciprocity are also tested as
      moderators of selection and socialization. METHOD: Cross-sequential study (three
      age cohorts assessed at three annual measurements) of 950 youth (53% male)
      initially attending classrooms in Grade 4 (n = 314; M = 10.1 years), Grade 7 (n =
      335; M = 13.1 years), and Grade 10 (n = 301; M = 16.2 years). RESULTS: Similarity
      between friends' drinking behaviors emerged in Grade 6, peaked in Grade 8, and
      decreased throughout late adolescence. Adolescents in all three age groups
      selected peers with similar drinking behaviors, with effects being more robust
      for early-adolescent males and for late-adolescent females. Peers' alcohol use
      emerged as a significant predictor of middle-adolescent alcohol use and remained
      a significant predictor of individual drinking behaviors throughout late
      adolescence. Socialization did not differ as a function of gender or reciprocity.
      CONCLUSIONS: Alcohol-related peer selection was relatively more important than
      socialization in early-adolescent friendship networks; both mechanisms
      contributed to explaining similarity between the drinking behaviors of friends in
      middle and late adolescence. Effects of peer socialization emerged in middle
      adolescence and remained throughout late adolescence.

PMID- 22152667
TI  - Dynamics of friendship networks and alcohol use in early and mid-adolescence.
AB  - OBJECTIVE: Similarity in alcohol consumption among adolescent friends could be
      caused by the influence of friends or by the selection of friends who consume
      similar levels of alcohol. This article aims to disentangle influence and
      selection processes while specifically examining changes over time in these
      processes and possible differences between reciprocal and nonreciprocal
      friendships. METHOD: The design was longitudinal with four observations (Time 1
      Time 4 [T1-T4]). Data consisted of a longitudinal sample of 1,204 Finnish
      adolescents in 10 junior high schools. The main measurements were adolescents'
      friendship networks and alcohol consumption. For three successive periods, T1-T2,
      T2-T3, and T3-T4, actor-based models for the co-evolution of networks and
      behavior were analyzed (Mage: T1 = 13.6 years, T2 = 14.6 years, T3 = 15.6 years,
      T4 = 16.1 years). RESULTS: Selection, as well as influence processes, played an
      important role in adolescent alcohol consumption. Influence was found during the
      first period (T1-T2), whereas support for selection was found during the last two
      periods (T2-T3 and T3-T4). The strength of influence and selection processes did
      not differ for reciprocal and nonreciprocal friendships. CONCLUSIONS: The impact
      of selection and influence processes changed over time such that influence was
      only present during early adolescence, whereas selection was present during mid
      adolescence. During early adolescence, youngsters would benefit from learning to
      resist social influence. Alcohol-consumption prevention programs targeting mid
      adolescence should consider peer selection processes. These findings stress the
      importance of considering changes over time in future practice and research.

PMID- 22152668
TI  - Drug resistance and substance use among male and female adolescents in
      alternative secondary schools in Guanajuato, Mexico.
AB  - OBJECTIVE: Research is limited on the strategies that Mexican adolescents use to
      resist use of alcohol, cigarettes, and other drugs. Cultural norms and gender
      socialization patterns concerning the acceptability of use of various substances
      by women and men influence Mexican youths in their responses to offers of
      substances. This study explored the drug-resistance strategies used by youth in
      the central Mexican state of Guanajuato, how their use predicted patterns of
      substance use, and how these associations differed by gender. METHOD: The
      analysis used cross-sectional survey data from 702 (60% male) students enrolled
      in eight alternative secondary education school sites in 2007. Participants
      reported the drug-resistance behaviors they used to deal with offers of alcohol,
      cigarettes, and marijuana. Past-12-month use of the four drug-resistance
      strategies employed most often by U.S. youth-refuse, explain, avoid, and leave
      (R.E.A.L.)-and any other strategies were measured. Composite measures of lifetime
      and recent use of alcohol, cigarettes, and marijuana were predicted in
      multivariate ordinary least squares regression analyses. Models were tested with
      and without controls for the frequency that respondents were offered substances
      and introduced gender interaction effects. RESULTS: Controlling for substance use
      offers, more frequent use of a wide repertoire of R.E.A.L. strategies predicted
      less consumption of alcohol and cigarettes, and using non-R.E.A.L. strategies
      predicted less marijuana consumption. All of these relationships were either
      stronger for males than for females or significant for males only. CONCLUSIONS:
      Gender differences exist in the impact of R.E.A.L. strategies on substance use
      among youth in Mexico. Despite a narrowing gender gap in substance use in Mexico,
      large exposure to and susceptibility of substance use remains. Developing
      effective prevention programs in Mexico based on teaching appropriate drug
      resistance strategies and enhancing communication skills could aid in reducing
      substance use among Mexican adolescents.

PMID- 22152669
TI  - Hispanic Americans Baseline Alcohol Survey (HABLAS): effects of container size
      adjustments on estimates of alcohol consumption across Hispanic national groups.
AB  - OBJECTIVE: This study was conducted to examine discrepancies in alcohol
      consumption estimates between a self-reported standard quantity-frequency measure
      and an adjusted version based on respondents' typically used container size.
      METHOD: Using a multistage cluster sample design, 5,224 Hispanic individuals 18
      years of age and older were selected from the household population in five
      metropolitan areas of the United States: Miami, New York, Philadelphia, Houston,
      and Los Angeles. The survey-weighted response rate was 76%. Personal interviews
      lasting an average of 1 hour were conducted in respondents' homes in either
      English or Spanish. RESULTS: The overall effect of container adjustment was to
      increase estimates of ethanol consumption by 68% for women (range across Hispanic
      groups: 17%-99%) and 30% for men (range: 14%-42%). With the exception of female
      Cuban American, Mexican American, and South/Central American beer drinkers and
      male Cuban American wine drinkers, all percentage differences between unadjusted
      and container-adjusted estimates were positive. Second, container adjustments
      produced the largest change for volume of distilled spirits, followed by wine and
      beer. Container size adjustments generally produced larger percentage increases
      in consumption estimates for the higher volume drinkers, especially the upper
      tertile of female drinkers. CONCLUSIONS: Self-reported alcohol consumption based
      on standard drinks underreports consumption when compared with reports based on
      the amount of alcohol poured into commonly used containers.

PMID- 22152670
TI  - Use of the screening suggested by the National Institute on Alcohol Abuse and
      Alcoholism and of a newly derived tool for the detection of unhealthy alcohol
      drinkers among surgical patients.
AB  - OBJECTIVE: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has
      developed a two-question tool for the detection of unhealthy drinking (NIAAA-2Q)
      that investigates excessive alcohol consumption per single occasion. NIAAA-2Q can
      be commuted into a four-question tool (NIAAA-4Q) by the addition of two questions
      aimed at investigating excessive weekly alcohol intake. NIAAA-2Q and NIAAA-4Q may
      prove useful in busy settings such as an anesthesiological environment. However,
      to date, no study has evaluated their efficacy in a surgical setting. The purpose
      of this study was to evaluate the accuracy of NIAAA-2Q and NIAAA-4Q in detecting
      unhealthy drinking among surgical patients using the more complex Alcohol Use
      Disorders Identification Test (AUDIT) comprising 10 questions as the criterion
      method. METHOD: NIAAA-4Q and AUDIT were administered to 200 surgical patients by
      three anesthetists. RESULTS: A total of 23.5%, 12.5%, and 28.5% surgical patients
      were unhealthy drinkers according to AUDIT, NIAAA-2Q, and NIAAA-4Q, respectively.
      NIAAA-2Q negative and positive predictive values were 0.78 and 0.36,
      respectively, and positive and negative likelihood ratios were 1.80 and 0.90,
      respectively. NIAAA-4Q negative and positive predictive values were 0.93 and
      0.65, respectively, and positive and negative likelihood ratios were 6.00 and
      0.24, respectively. CONCLUSIONS: NIAAA-4Q demonstrated a better satisfactory
      agreement than NIAAA-2Q with AUDIT in detecting unhealthy alcohol drinking among
      surgical patients. These results suggest that the detection of unhealthy alcohol
      drinking may be increased by the administration of questions aimed at assessing
      the weekly average of alcohol intake. The modest time required for NIAAA-4Q
      administration is a major advantage in clinical practice with respect to AUDIT.
      Further research will compare NIAAA-2Q and NIAAA-4Q with other brief alcohol
      screening tests.

PMID- 22152671
TI  - Implicit cognition and substance use: the role of controlled and automatic
      processes in children.
AB  - OBJECTIVE: Most cognitive models of substance abuse and dependence posit that
      controlled and automatic processes are central to substance use. Tests of these
      models rely on methods that are interpreted to measure one or the other of these
      processes. There has been growing interest in the use of implicit substance use
      tasks, which are posited to reflect automatic processes. Recent model
      advancements suggest that behavior is determined by multiple cognitive processes
      and that dual-process models may provide an overly simplistic account of the
      cognitive process involved in the assessment of implicit cognition. The goal of
      the current study was to apply the Quad Model to children's performance on
      implicit substance use tasks and consider associations with early substance use.
      METHOD: Children (N = 378; 52% girls) ranging from 10 to 12 years old completed
      alcohol and cigarette Single Category Implicit Association Tests (SC-IATs) and
      self-reports of substance use. RESULTS: Four distinct cognitive processes were
      found to influence SC-IAT performance, one of which reflected automatic
      activation, the process typically viewed as central to IAT performance.
      Differences across drinking status revealed weaker automatic activation of
      negative alcohol associations for those who had (vs. had not) initiated drinking,
      and a strong likelihood to overcome biased attitudes was supported for all
      children. The low prevalence of cigarette use in our young sample prohibited
      examination of the model across smoking status. CONCLUSIONS: Findings suggest
      that performance on implicit substance use tasks is not process pure. Quantifying
      and interpreting the multiple influencing processes are crucial for further
      development and evaluation of cognitive risk models of substance use.

PMID- 22152672
TI  - Sources of biased inference in alcohol and drug services research: an
      instrumental variable approach.
AB  - OBJECTIVE: This study examined the potential for biased inference due to
      endogeneity when using standard approaches for modeling the utilization of
      alcohol and drug treatment. METHOD: Results from standard regression analysis
      were compared with those that controlled for endogeneity using instrumental
      variables estimation. Comparable models predicted the likelihood of receiving
      alcohol treatment based on the widely used Aday and Andersen medical care-seeking
      model. Data were from the National Epidemiologic Survey on Alcohol and Related
      Conditions and included a representative sample of adults in households and group
      quarters throughout the contiguous United States. RESULTS: Findings suggested
      that standard approaches for modeling treatment utilization are prone to bias
      because of uncontrolled reverse causation and omitted variables. Compared with
      instrumental variables estimation, standard regression analyses produced
      downwardly biased estimates of the impact of alcohol problem severity on the
      likelihood of receiving care. CONCLUSIONS: Standard approaches for modeling
      service utilization are prone to underestimating the true effects of problem
      severity on service use. Biased inference could lead to inaccurate policy
      recommendations, for example, by suggesting that people with milder forms of
      substance use disorder are more likely to receive care than is actually the case.

PMID- 22152673
TI  - Computer Assessment of Simulated Patient Interviews (CASPI): psychometric
      properties of a web-based system for the assessment of motivational interviewing
      skills.
AB  - OBJECTIVE: Benefits of empirically supported interventions hinge on clinician
      skill, particularly for motivational interviewing (MI). Existing MI skill
      assessments are limited with respect to validity (e.g., self-report) and
      practicality (e.g., coding session tapes). To address these limitations, we
      developed and evaluated two versions of a web-based assessment of MI skills, the
      Computer Assessment of Simulated Patient Interviews (CASPI). METHOD: Ninety-six
      counselors from the community and 24 members of the Motivational Interviewing
      Network of Trainers (MINT) completed the CASPI (N = 120), in which they verbally
      responded via microphones to video clips comprising three 9-item vignettes. Three
      coders used an emergent coding scheme, which was compared with alternative MI
      skills measures. RESULTS: CASPI demonstrated excellent internal consistency when
      averaging across two or three vignettes (alpha's = .86-.89). Intraclass
      correlations were above .40 for most items. Confirmatory factor analyses
      supported a correlated three-factor model: MI-consistent, resistance-engendering,
      and global change talk orientation rating. Means and factor loadings were
      invariant across forms (i.e., the two alternative versions of CASPI), and factor
      loadings were invariant across subgroup (i.e., community counselor or MINT
      member). Test-retest reliability was good for MI-consistent and resistance
      engendering scores (r = .74 and .80, respectively) but low for change talk
      orientation (r = .29) unless coder was taken into account (r = .69). CASPI showed
      excellent construct and criterion-related validity. CONCLUSIONS: CASPI represents
      a promising method of assessing MI skills. Future studies are needed to establish
      its performance in real-world contexts.

PMID- 22152674
TI  - Parasites of vectors--Ixodiphagus hookeri and its Wolbachia symbionts in ticks in
      The Netherlands.
AB  - BACKGROUND: Ixodiphagus hookeri is a parasitic wasp of ixodid ticks around the
      world. It has been studied as a potential bio-control agent for several tick
      species. We suspected that the presence of Wolbachia infected I. hookeri eggs in
      ticks is responsible for incidental detection of Wolbachia DNA in tick samples.
      METHODS: The 28S rRNA and 16S rRNA genes of a specimen of I. hookeri was
      amplified and sequenced. PCR on part of the 28S rRNA gene was used to detect
      parasitic wasp DNA in 349 questing Ixodes ricinus ticks from various sampling
      sites. Furthermore, the wsp gene of Wolbachia was sequenced from the I. hookeri
      specimen and a subset of ticks was tested using this marker. RESULTS: Several
      sequences from tick specimens were identical to the Wolbachia sequence of the I.
      hookeri specimen. Ixodiphagus hookeri was detected in 9.5% of all tested ticks,
      varying between 4% and 26% depending on geographic location. Ten out of eleven
      sampling sites throughout the Netherlands were positive for I. hookeri. Eighty
      seven percent of I. hookeri-positive but only 1.6% of I. hookeri-negative ticks
      were Wolbachia positive. Detection of I. hookeri DNA was strongly associated with
      the detection of Wolbachia in ticks. CONCLUSION: This is the first reported case
      of I. hookeri in the Netherlands. Furthermore I. hookeri harbours Wolbachia
      species and is broadly distributed in the Netherlands. While detection of
      Wolbachia DNA in ticks might often be due to parasitism with this wasp, other
      sources of Wolbachia DNA in ticks might exist as well.

PMID- 22152676
TI  - Shared and unique components of human population structure and genome-wide
      signals of positive selection in South Asia.
AB  - South Asia harbors one of the highest levels genetic diversity in Eurasia, which
      could be interpreted as a result of its long-term large effective population size
      and of admixture during its complex demographic history. In contrast to Pakistani
      populations, populations of Indian origin have been underrepresented in previous
      genomic scans of positive selection and population structure. Here we report data
      for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups
      in India. Combining our results with other available genome-wide data, we show
      that Indian populations are characterized by two major ancestry components, one
      of which is spread at comparable frequency and haplotype diversity in populations
      of South and West Asia and the Caucasus. The second component is more restricted
      to South Asia and accounts for more than 50% of the ancestry in Indian
      populations. Haplotype diversity associated with these South Asian ancestry
      components is significantly higher than that of the components dominating the
      West Eurasian ancestry palette. Modeling of the observed haplotype diversities
      suggests that both Indian ancestry components are older than the purported Indo
      Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic
      distances among world regions, Indians share more ancestry signals with West than
      with East Eurasians. However, compared to Pakistani populations, a higher
      proportion of their genes show regionally specific signals of high haplotype
      homozygosity. Among such candidates of positive selection in India are MSTN and
      DOK5, both of which have potential implications in lipid metabolism and the
      etiology of type 2 diabetes.

PMID- 22152675
TI  - TMEM237 is mutated in individuals with a Joubert syndrome related disorder and
      expands the role of the TMEM family at the ciliary transition zone.
AB  - Joubert syndrome related disorders (JSRDs) have broad but variable phenotypic
      overlap with other ciliopathies. The molecular etiology of this overlap is
      unclear but probably arises from disrupting common functional module components
      within primary cilia. To identify additional module elements associated with
      JSRDs, we performed homozygosity mapping followed by next-generation sequencing
      (NGS) and uncovered mutations in TMEM237 (previously known as ALS2CR4). We show
      that loss of the mammalian TMEM237, which localizes to the ciliary transition
      zone (TZ), results in defective ciliogenesis and deregulation of Wnt signaling.
      Furthermore, disruption of Danio rerio (zebrafish) tmem237 expression produces
      gastrulation defects consistent with ciliary dysfunction, and Caenorhabditis
      elegans jbts-14 genetically interacts with nphp-4, encoding another TZ protein,
      to control basal body-TZ anchoring to the membrane and ciliogenesis. Both
      mammalian and C. elegans TMEM237/JBTS-14 require RPGRIP1L/MKS5 for proper TZ
      localization, and we demonstrate additional functional interactions between C.
      elegans JBTS-14 and MKS-2/TMEM216, MKSR-1/B9D1, and MKSR-2/B9D2. Collectively,
      our findings integrate TMEM237/JBTS-14 in a complex interaction network of TZ
      associated proteins and reveal a growing contribution of a TZ functional module
      to the spectrum of ciliopathy phenotypes.

PMID- 22152677
TI  - Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal
      dysplasia with joint laxity, leptodactylic type.
AB  - Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL), leptodactylic (lepto
      SEMDJL) or Hall type, is an autosomal-dominant skeletal dysplasia manifesting
      with short stature, joint laxity with dislocation(s), limb malalignment, and
      spinal deformity. Its causative gene mutation has not yet been discovered. We
      captured and sequenced the exomes of eight affected individuals in six unrelated
      kindreds (three individuals in a family and five simplex individuals). Five novel
      sequence variants in KIF22, which encodes a member of the kinesin-like protein
      family, were identified in seven individuals. Sanger sequencing of KIF22
      confirmed that c.443C>T (p.Pro148Ser) cosegregated with the phenotype in the
      affected individuals in the family; c.442C>T (p.Pro148Leu) or c.446G>A
      (p.Arg149Gln) was present in four of five simplex individuals, but was absent in
      unaffected individuals in their family and 505 normal cohorts. KIF22 mRNA was
      detected in human bone, cartilage, joint capsule, ligament, skin, and primary
      cultured chondrocytes. In silico analysis of KIF22 protein structure indicates
      that Pro148 and Arg149 are important in maintaining hydrogen bonds in the ATP
      binding and motor domains of KIF22. We conclude that these mutations in KIF22
      cause lepto-SEMDJL.

PMID- 22152678
TI  - Recurrent dominant mutations affecting two adjacent residues in the motor domain
      of the monomeric kinesin KIF22 result in skeletal dysplasia and joint laxity.
AB  - Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto
      SEMDJL, aka SEMDJL, Hall type), is an autosomal dominant skeletal disorder that,
      in spite of being relatively common among skeletal dysplasias, has eluded
      molecular elucidation so far. We used whole-exome sequencing of five unrelated
      individuals with lepto-SEMDJL to identify mutations in KIF22 as the cause of this
      skeletal condition. Missense mutations affecting one of two adjacent amino acids
      in the motor domain of KIF22 were present in 20 familial cases from eight
      families and in 12 other sporadic cases. The skeletal and connective tissue
      phenotype produced by these specific mutations point to functions of KIF22 beyond
      those previously ascribed functions involving chromosome segregation. Although we
      have found Kif22 to be strongly upregulated at the growth plate, the precise
      pathogenetic mechanisms remain to be elucidated.

PMID- 22152679
TI  - Homozygosity mapping and candidate prioritization identify mutations, missed by
      whole-exome sequencing, in SMOC2, causing major dental developmental defects.
AB  - Inherited dental malformations constitute a clinically and genetically
      heterogeneous group of disorders. Here, we report on a severe developmental
      dental defect that results in a dentin dysplasia phenotype with major
      microdontia, oligodontia, and shape abnormalities in a highly consanguineous
      family. Homozygosity mapping revealed a unique zone on 6q27-ter. The two affected
      children were found to carry a homozygous mutation in SMOC2. Knockdown of smoc2
      in zebrafish showed pharyngeal teeth that had abnormalities reminiscent of the
      human phenotype. Moreover, smoc2 depletion in zebrafish affected the expression
      of three major odontogenesis genes: dlx2, bmp2, and pitx2.

PMID- 22152680
TI  - Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective
      mitochondrial energy metabolism, and glycine elevation.
AB  - Lipoic acid is an essential prosthetic group of four mitochondrial enzymes
      involved in the oxidative decarboxylation of pyruvate, alpha-ketoglutarate, and
      branched chain amino acids and in the glycine cleavage. Lipoic acid is
      synthesized stepwise within mitochondria through a process that includes lipoic
      acid synthetase. We identified the homozygous mutation c.746G>A (p.Arg249His) in
      LIAS in an individual with neonatal-onset epilepsy, muscular hypotonia, lactic
      acidosis, and elevated glycine concentration in plasma and urine. Investigation
      of the mitochondrial energy metabolism showed reduced oxidation of pyruvate and
      decreased pyruvate dehydrogenase complex activity. A pronounced reduction of the
      prosthetic group lipoamide was found in lipoylated proteins.

PMID- 22152681
TI  - Dissecting the genetics of complex inheritance: linkage disequilibrium mapping
      provides insight into Crohn disease.
AB  - Family studies for Crohn disease (CD) report extensive linkage on chromosome 16q
      and pinpoint NOD2 as a possible causative locus. However, linkage is also
      observed in families that do not bear the most frequent NOD2 causative mutations,
      but no other signals on 16q have been found so far in published genome-wide
      association studies. Our aim is to identify this missing genetic contribution. We
      apply a powerful genetic mapping approach to the Wellcome Trust Case-Control
      Consortium and the National Institute of Diabetes and Digestive and Kidney
      Diseases genome-wide association data on CD. This method takes into account the
      underlying structure of linkage disequilibrium (LD) by using genetic distances
      from LD maps and provides a location for the causal agent. We find genetic
      heterogeneity within the NOD2 locus and also show an independent and unsuspected
      involvement of the neighboring gene, CYLD. We find associations with the IRF8
      region and the region containing CDH1 and CDH3, as well as substantial phenotypic
      and genetic heterogeneity for CD itself. The genes are known to be involved in
      inflammation and immune dysregulation. These findings provide insight into the
      genetics of CD and suggest promising directions for understanding disease
      heterogeneity. The application of this method thus paves the way for
      understanding complex inheritance in general, leading to the dissection of
      different pathways and ultimately, personalized treatment.

PMID- 22152682
TI  - Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in
      the pyruvate oxidation pathway.
AB  - Thiamine pyrophosphate (TPP) is an essential cofactor of the cytosolic
      transketolase and of three mitochondrial enzymes involved in the oxidative
      decarboxylation of either pyruvate, alpha-ketoglutarate or branched chain amino
      acids. Thiamine is taken up by specific transporters into the cell and converted
      to the active TPP by thiamine pyrophosphokinase (TPK) in the cytosol from where
      it can be transported into mitochondria. Here, we report five individuals from
      three families presenting with variable degrees of ataxia, psychomotor
      retardation, progressive dystonia, and lactic acidosis. Investigation of the
      mitochondrial energy metabolism showed reduced oxidation of pyruvate but normal
      pyruvate dehydrogenase complex activity in the presence of excess TPP. A reduced
      concentration of TPP was found in the muscle and blood. Mutation analysis of TPK1
      uncovered three missense, one splice-site, and one frameshift mutation resulting
      in decreased TPK protein levels.

PMID- 22152683
TI  - Disruption of teashirt zinc finger homeobox 1 is associated with congenital aural
      atresia in humans.
AB  - Congenital aural atresia (CAA) can occur as an isolated congenital malformation
      or in the context of a number of monogenic and chromosomal syndromes. CAA is
      frequently seen in individuals with an 18q deletion, which is characterized by
      intellectual disability, reduced white-matter myelination, foot deformities, and
      distinctive facial features. Previous work has indicated that a critical region
      for CAA is located in 18q22.3. We studied four individuals (from two families)
      with CAA and other features suggestive of an 18q deletion, and we detected
      overlapping microdeletions in 18q22.3 in both families. The minimal region of
      deletion overlap (72.9-73.4 Mb) contained only one known gene, TSHZ1, which was
      recently shown to be important for murine middle-ear development. Sequence
      analysis of the coding exons in TSHZ1 in a cohort of 11 individuals with
      isolated, nonsyndromic bilateral CAA revealed two mutations, c.723G>A (p.Trp241X)
      and c.946_947delinsA (p.Pro316ThrfsX16), and both mutations predicted a loss of
      function. Together, these results demonstrate that hemizygosity of TSHZ1 leads to
      congenital aural atresia as a result of haploinsufficiency.

PMID- 22152685
TI  - Struma ovarii presenting with Hashimoto's thyroiditis: a case report.
AB  - INTRODUCTION: We report the case of a patient diagnosed with a struma ovarii with
      lymphocytic thyroiditis of her ectopic thyroid tissue. We believe that this case
      presents an unusual variation of a struma ovarii and a rare presentation of
      subclinical hyperthyroidism. CASE PRESENTATION: A 17-year-old Caucasian female
      patient who had undergone an ovariectomy and been diagnosed with a struma ovarii
      was subsequently found to have persistent subclinical hyperthyroidism with a low
      radioiodine uptake. Abdominal magnetic resonance imaging and iodine-131 whole
      body scanning showed no residue or recurrence and a thyroid ultrasonography was
      normal. Laboratory and histopathological findings suggested Hashimoto's
      thyroiditis as the cause of the subclinical thyrotoxicosis, which had presumably
      started at the ectopic tissue. CONCLUSION: Struma ovarii is a rare cause of
      thyrotoxicosis, and can be difficult to diagnose in the presence of co-existing
      thyroid disorders. In patients with a struma ovarii who have not undergone
      thyroidectomy, there is no common consensus on management in terms of residue,
      recurrence or metastasis. Autoimmune thyroiditis must be kept in mind for a
      differential diagnosis.

PMID- 22152684
TI  - Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil
      cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil
      adhesion and impairs migration.
AB  - INTRODUCTION: In anti-neutrophil cytoplasmic autoantibody (ANCA)-associated
      vasculitides (AAV), persistent inflammation within the vessel wall suggests
      perturbed neutrophil trafficking leading to accumulation of activated neutrophils
      in the microvascular compartment. CXCR1 and CXCR2, being major chemokine
      receptors on neutrophils, are largely responsible for neutrophil recruitment. We
      speculate that down-regulated expression of CXCR1/2 retains neutrophils within
      the vessel wall and, consequently, leads to vessel damage. METHODS: Membrane
      expression of CXCR1/2 on neutrophils was assessed by flow cytometry. Serum levels
      of interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), angiopoietin 1
      and angiopoietin 2 from quiescent and active AAV patients and healthy controls
      (HC) were quantified by ELISA. Adhesion and transendothelial migration of
      isolated neutrophils were analyzed using adhesion assays and Transwell systems,
      respectively. RESULTS: Expression of CXCR1 and CXCR2 on neutrophils was
      significantly decreased in AAV patients compared to HC. Levels of IL-8, which, as
      TNFalpha, dose-dependently down-regulated CXCR1 and CXCR2 expression on
      neutrophils in vitro, were significantly increased in the serum of patients with
      active AAV and correlated negatively with CXCR1/CXCR2 expression on neutrophils,
      even in quiescent patients. Blocking CXCR1 and CXCR2 with repertaxin increased
      neutrophil adhesion and inhibited migration through a glomerular endothelial cell
      layer. CONCLUSIONS: Expression of CXCR1 and CXCR2 is decreased in AAV,
      potentially induced by circulating proinflammatory cytokines such as IL-8. Down
      regulation of these chemokine receptors could increase neutrophil adhesion and
      impair its migration through the glomerular endothelium, contributing to
      neutrophil accumulation and, in concert with ANCA, persistent inflammation within
      the vessel wall.

PMID- 22152686
TI  - Suspected transmission of norovirus in eight long-term care facilities attributed
      to staff working at multiple institutions.
AB  - This study reports on gastroenteritis outbreaks suspected of being norovirus
      infections in eight long-term care facilities. A descriptive epidemiological
      investigation was used to depict sources of infections and control measures.
      Outbreaks affected 299 (31%) of 954 residents and 95 (11%) of 843 staff. Attack
      rates were higher in residents (range 17-55%) than staff (range 3-35%). Person-to
      person spread was suspected. The case-hospitalization rate was 2.5%, and no death
      occurred. Eight staff members were employed at multiple affected facilities and
      may have introduced disease into three facilities. Thirty-two stool specimens
      were positive for norovirus by real-time reverse transcriptase-polymerase chain
      reaction or enzyme immunoassay. Sequenced specimens were closely related to GII.4
      New Orleans. A concurrent Clostridium difficile outbreak was also detected at one
      facility. Staff members who work at multiple facilities may transmit norovirus
      between them. Regulatory agencies should consider precluding ill staff from
      working in multiple facilities during outbreaks. Guidelines to control norovirus
      must be applied promptly and meticulously by facilities.

PMID- 22152687
TI  - Vetufebrus ovatus n. gen., n. sp. (Haemospororida: Plasmodiidae) vectored by a
      streblid bat fly (Diptera: Streblidae) in Dominican amber.
AB  - BACKGROUND: Both sexes of bat flies in the families Nycteribiidae and Streblidae
      (Diptera: Hippoboscoidea) reside in the hair or on the wing membranes of bats and
      feed on blood. Members of the Nycteribiidae transmit bat malaria globally however
      extant streblids have never been implemented as vectors of bat malaria. The
      present study shows that during the Tertiary, streblids also were vectors of bat
      malaria. RESULTS: A new haemospororidan, Vetufebrus ovatus, n. gen., n. sp.,
      (Haemospororida: Plasmodiidae) is described from two oocysts attached to the
      midgut wall and sporozoites in salivary glands and ducts of a fossil bat fly
      (Diptera: Streblidae) in Dominican amber. The new genus is characterized by ovoid
      oocysts, short, stubby sporozoites with rounded ends and its occurrence in a
      fossil streblid. This is the first haemosporidian reported from a streblid bat
      fly and shows that representatives of the Hippoboscoidea were vectoring bat
      malaria in the New World by the mid-Tertiary. CONCLUSIONS: This report is the
      first evidence of an extant or extinct streblid bat fly transmitting malaria.
      Discovering a mid-tertiary malarial parasite in a fossil streblid that closely
      resembles members of a malarial genus found in nycteribiid bat flies today shows
      how little we know about the vector associations of streblids. While no malaria
      parasites have been found in extant streblids, they probably occur and it is
      possible that streblids were the earliest lineage of flies that transmitted bat
      malaria to Chiroptera.

PMID- 22152688
TI  - [Effect of shRNA Survivin-mediated inhibition of proliferation in A549 cells].
AB  - BACKGROUND AND OBJECTIVE: Survivin is a member of the inhibitor of apoptosis
      family of proteins. The Survivin protein is highly expressed in most human
      tumors, but it is completely absent in terminally differentiated cells.
      Consequently, Survivin is an ideal target for cancer therapy because cancer cells
      are targeted and normal cells are left alone. The aim of this study is to
      construct a lentivirus-shRNA vector, and to disrupt the expression of Survivin in
      A549 cells. The effect of sh-RNA Survivin on A549 cells was analyzed. METHODS:
      Target DNA sequences of Survivin shRNA were designed to obtain recombinant
      plasmids. After the plasmids were transfected into 293T cells, the virus was
      collected. Hela cells were used to detect the virus titer. Survivin mRNA and
      protein expression in the infected A549 cells were detected via reverse
      transcription polymerase chain reaction and Western blot analysis. The
      proliferation of A549 cells were detected via 3-(4,5-dimethylthiazolyl)-2,5
      diphenyltetrazolium bromide and flow cytometry assays. RESULTS: The recombinants
      were successfully constructed, and Survivin expression was inhibited. The cells
      were blocked at the G2/M phase. CONCLUSIONS: Recombinant lentivirus with shRNA
      targeting Survivin was successfully constructed. The lentivirus can down-regulate
      Survivin expression in A549 cells as well as inhibit proliferation, and is hence
      a potential gene therapy for lung cancer.

PMID- 22152689
TI  - [Influence of anxiety and depression status of family members on the general
      psychological status of perioperative patients with lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Facing the double pressures caused by cancer and
      surgery, many patients will appear series psychological problems like nervous,
      fear, pessimism, anxiety and so on. The aim of this study is to explone the
      anxiety, depression status of family members, the general psychological status of
      perioperative patients with lung cancer and the influence of the former on the
      latter. METHODS: Total 97 patients and 97 patient family members from the
      thoracic department of the Second Xiangya Hospital of Central South University
      were enrolled as the study subjects. The general information, the anxiety and
      depression status of the family members, and the general psychological status of
      perioperative patients with lung cancer were investigated using self-made general
      information questionnaire, self-rating anxiety scale (SAS), self-rating
      depression scale (SDS) and symptom check-list 90 (SCL-90). RESULTS: The scores of
      seven factors, including total scores (153.28+/-41.98), somatization (1.78+/
      0.42), compulsion (1.96+/-0.52), depression (1.77+/-0.67), anxiety (1.82+/-0.56),
      hostility (1.68+/-0.87), panic (1.44+/-0.75) and psychosis (1.56+/-0.51) in SCL
      90 were remarkerbly higher than those in domestic norm (P<0.05). The standard
      score in SAS of the family members was positively correlated with the compulsion,
      anxiety and bigoted factors of SCL-90 in the patients (P<0.05). The depression
      severity of the family members was negatively correlated with the compulsion and
      psychosis factors of SCL-90 in the patients (P<0.05). CONCLUSIONS: Family members
      have different degrees of anxiety and depression, which have certain effects on
      the general psychological status of perioperative patients with lung cancer.

PMID- 22152690
TI  - [Effect of the XRCC1 and XRCC3 genetic polymorphisms on the efficacy of platinum
      based chemotherapy in patients with advanced non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: DNA repair gene polymorphisms can be used to predict
      the sensitivity of platinum-based chemotherapy. Thus, such polymorphisms are
      important for the individual treatment of non-small cell lung cancer (NSCLC). The
      aim of this study is to investigate the relationship between X-ray repair cross
      complementing protein 1 (XRCC1) and X-ray repair cross complementing protein 3
      (XRCC3) gene polymorphisms and the chemosensitivity of platinum-based
      chemotherapy in patients with advanced NSCLC. METHODS: Genomic DNA were extracted
      from the sera of a total of 130 patients with advanced NSCLC who received
      platinum-based chemotherapy. XRCC1 Arg194 Trp, Arg399 Gln, and XRCC3 Thr241 Met
      were genotyped using the polymerase chain reaction-restriction fragment length
      polymorphism method, and the relationship between XRCC1 and XRCC3 polymorphisms
      and chemotherapy sensitivity was analyzed. RESULTS: A total of 130 patients with
      advanced NSCLC received platinum-based chemotherapy, with an overall response
      rate of 33.8% after two chemotherapy cycles. The XRCC1 194 and 399 genetic
      polymorphisms, but not XRCC3 241, were found to be related to the
      chemosensitivity. The objective response rate of the patients with at least one
      XRCC1 194 Trp allele was 2.5 times higher than that of Arg/Arg genotype carriers
      (42.1% vs 22.2%, OR=2.545, 95%CI: 1.159-5.590, P=0.020). The objective response
      rate of the XRCC1 399 Arg/Arg genotype carriers was significantly higher than
      that of the patients with at least one Gln allele (45.5% vs 21.9%, OR=0.336,
      95%CI: 0.156-0.722, P=0.005). Combined effects between XRCC1 194 and XRCC1 399
      were observed. The objective response rate of the patients with at least one
      XRCC1 194 Trp allele and a 399 Arg/Arg genotype was significantly higher than
      that of patients with 194 Arg/Arg and 399 Arg/Gln genotypes (44.4% vs 18.8%,
      OR=3.467, 95%CI: 1.223-9.782, P=0.019). Moreover, XRCC1 and XRCC3 have a combined
      effect in predicting chemosensitivity. Patients with XRCC3 241 Thr/Met, 399
      Arg/Arg, and at least one XRCC1 194 Trp allele simultaneously showed an improved
      objective response rate. CONCLUSIONS: The combination of the XRCC1 and XRCC3
      polymorphisms may be associated with patient sensitivity to platinum-based
      chemotherapy in advanced NSCLC.

PMID- 22152691
TI  - [Expression of CD82/KAI1 and HIF-1alpha in non-small cell lung cancer and their
      relationship to vasculogenic mimicry].
AB  - BACKGROUND AND OBJECTIVE: Vasculogenic mimicry (VM), found in many high invasive
      ability tumors, is associated with tumor invasion and metastasis. Many genes
      exhibit abnormal levels of expression in these tumors. This study aims to find
      good markers for predicting the invasion and metastasis of non-small cell lung
      cancer (NSCLC). METHODS: VM and expression of CD82/KAI1 and HIF-1alpha were
      examined via immunohistochemistry and histochemistry of 160 NSCLC and 20 normal
      lung tissue specimens. RESULTS: In NSCLC, positive rates of 37.5%, 48.8%, and
      36.9% were obtained for CD82/KAI1, HIF-1alpha, and VM, respectively. In normal
      lung tissue, positive rates of 95.0%, 0, and 0 were obtained for CD82/KAI1, HIF
      1alpha, and VM, respectively. A significant difference was found between the
      NSCLC and normal lung groups (P<0.01). VM and the expression levels of CD82/KAI1
      and HIF-1alpha were significantly related to tumor differentiation, lymph node
      metastasis, clinical staging, and postoperative survival time (P<0.01 for all). A
      negative correlation was found between the expression levels of CD82/KAI1 and HIF
      1alpha; a similar relationship was observed between CD82/KAI1 and VM. A positive
      relationship between the expression of HIF-1alpha and VM was revealed; there was
      a significant relationship between microvessel density (MVD) and the expression
      of CD82/KAI1 or HIF-1alpha or VM. VM and overexpression of HIF-1alpha were
      related to poor prognosis: the survival rates were significantly lower in
      positive patients than in negative patients (both P<0.01). The survival rates of
      the CD82/KAI1-positive and CD82/KAI1-negative groups were significantly different
      (P<0.01). The five-year survival rate was significantly different between the
      group with MVD>=22 and the group with MVD<22 (P<0.01). pTNM stage, positive
      expressions of CD82/KAI1 and HIF-1alpha, and VM were independent prognostic
      factors of NSCLC (P<0.01). CONCLUSIONS: VM and the expressions of CD82/KAI1 and
      HIF-1alpha in NSCLC are related to differentiation, lymph node metastasis,
      clinical staging, and prognosis. The combined detection of CD82/KAI1, HIF-1alpha,
      and VM has an important role in predicting the progression and prognosis of
      NSCLC.

PMID- 22152692
TI  - [Multivariate survival analysis of patients with stage I NSCLC].
AB  - BACKGROUND AND OBJECTIVE: The effectiveness of adjuvant chemotherapy in providing
      survival advantage for stage I non-small cell lung cancer (NSCLC) patients,
      especially those with stage Ib NSCLC, remains to be determined. The seventh
      edition of the Tumor Node Metastasis (TNM) Classification of Malignant Tumors is
      due to be published in 2009. The aim of the current study is to validate the
      value of this classification in Chinese early-stage NSCLC. The benefits of
      adjuvant chemotherapy to patients with early-stage NSCLC were also assessed.
      METHODS: The new staging project was validated in 433 patients who underwent
      complete surgical resection for early-stage NSCLC at the Single Institution of
      Shanghai Chest Hospital from June 1998 to June 2010. This new parameter was
      combined with other well-established prognostic factors, and multivariate
      survival analysis were performed. Variables in the analysis included age, gender,
      history of smoking, pathologic type, type of resection (pneumonectomy, lobectomy,
      bilobectomy, and sleeve resection), tumor size (largest tumor dimension), T
      status, lymphovascular vessel invasion, and adjuvant chemotherapy. RESULTS: The
      three-year overall survival rates for females and males are 89.22% and 77.53%,
      respectively (P=0.001,8). Elder patients have worse prognoses: the survival rates
      for those aged >=70 and <70 are 70.64% and 85.85%, respectively (P=0.000,1). The
      three-year overall survival rates of patients whose tumors measured no larger
      than 2 cm in biggest diameter or larger than 2 cm but no larger than 3 cm are
      95.15% and 85.71%, respectively. For those with tumors larger than 3 cm but
      smaller than 5 cm or larger than 5 cm but smaller than 7 cm, the survival rates
      are 74.80% and 60.47%, respectively (P<0.000,1). Multivariate analysis reveals
      that age, gender, vascular vessel invasion, pathologic type, and visceral pleural
      involvement are significant predictive factors of the overall survival.
      CONCLUSIONS: The tumor size and pathologic type are significant independent
      prognostic factors in stage I NSCLC. The survival rates of patients with
      adenocarcinoma are higher than those of patients with other types of NSCLC.
      Female patients and those without a history of smoking have a better outcome.
      Results suggest that patients with the Ib stage of the disease can benefit from
      adjuvant chemotherapy.

PMID- 22152693
TI  - [Radioactive seed implantation for the treatment of mediastinal malignant tumors
      and lymph node metastases in 43 cases].
AB  - BACKGROUND AND OBJECTIVE: The locations of mediastinal malignant tumor lesions
      are deep and occult, and are close to the pericardium, trachea, or major vessels.
      Therefore, the possibility of surgical resection is slim, and cryoablation and
      thermal ablation are restricted. In current study, image and life quality data
      were compared before and after 125I seeding therapy to investigate its safety and
      clinical effects. METHODS: From July 2010 to July 2011, a 43-patient follow-up of
      pathologically confirmed cancers, including 21 cases of primary mediastinal
      squamous lung cancer, 9 cases of primary esophagus cancer, and 13 cases of lymph
      node metastases were completed. Among these, 18 cases presented with tracheal
      stenosis >50%, 9 cases had esophageal obstruction, and 9 cases had superior vena
      cava reflux disorder. Each lesion was implanted with 10 to 60 pieces of 125I
      particles, with an average of 30.79+/-14.23. CT data at 2, 4, 6, and 12 months
      after therapy were obtained to evaluate the local lesion outcome. The quality of
      life of the patients as well as survival data was also recorded. RESULTS: The
      overall success rate of the operation was 100%. The longest time of follow-up was
      12 months. At 6 months, 37 patients were alive, and the half-year survival rate
      was 85.0%. In terms of local lesions, 30 cases of PR and 7 cases of NC were
      found. The clinical effective rate was 81.08%, and the clinical beneficial rate
      was 100%. At 12 months after therapy, 31 patients were alive, and the one-year
      survival rate was 60.5%. In terms of local lesions, 16 cases of CR, 7 cases of
      PR, 2 cases of NC, and 6 cases of PD were found. The clinical effective rate was
      74.19%, and the clinical beneficial rate was 80.65%. The KPS score increased
      after the treatment (P=0.000). Three cases of pneumothorax presented after
      treatment, and no severe complications, such as vessel, trachea, recurrent
      laryngeal nerve, or pericardiocentesis injuries, were found. CONCLUSIONS:
      Radiation seed implantation in mediastinal malignant tumors is a relatively safe
      technique with high success rate, considerable efficacy, and clear clinical value
      in advanced cancer treatment.

PMID- 22152694
TI  - [Detecting overexpression level of HER2 gene in NSCLC by real-time quantitative
      PCR and the 2[-Delta Delta C(T)] method].
AB  - BACKGROUND AND OBJECTIVE: The evaluation of the expression level of the HER2 gene
      for the diagnosis and treatment of tumors is usually conducted using
      immunohistochemical techniques. The aim of the current study is to explore the
      feasibility of real-time quantitative PCR and the 2[-Delta Delta C(T)] method in
      detecting the level of HER2 gene overexpression in non-small cell lung cancer
      (NSCLC). METHODS: Real-time quantitative PCR and the 2[-Delta Delta C(T)] method
      were used to detect the level of HER2 gene overexpression in 212 lung cancer and
      matched non-tumor tissue specimens. RESULTS: The expression level of HER2 gene in
      lung cancer tissue was higher than that in the matched non-tumor tissue, with an
      overexpression rate of 34%. CONCLUSIONS: Real-time quantitative PCR and the 2[
      Delta Delta C(T)] method can be used to detect the level of HER2 gene
      overexpression in NSCLC.

PMID- 22152695
TI  - [Advances of medical treatment in advanced non-small cell lung cancer in 2011
      American Society of Clinical Oncology Annual Meeting].

PMID- 22152696
TI  - [Advances of treatment about elderly clinical stage I non-small cell lung
      cancer].
AB  - With the aging of the population, the proportion of elderly lung cancer is
      increasing. More than ten years, lobectomy with mediastinal lymph node dissection
      has been the standard surgery for stage I non-small cell lung cancer (NSCLC).
      However, recent studies found that sublobectomy could get the same long-term
      outcome with the lobectomy for elderly clinical stage I NSCLC and more normal
      lung tissue could be retained. It becomes controversial again about the standard
      surgery of stage I NSCLC at present. Elderly stage I NSCLC is a special group,
      who often can not tolerate thoracotomy because of the poor body function and some
      comorbidities, but the thoracoscopic surgery and the stereotactic radiotherapy
      technology (STRT) supply them more options. The treatment of eldly stage I NSCLC
      is developing towards to the individualization and diversification.

PMID- 22152697
TI  - [Researche advances on CIK cells and their clinical use in lung cancer].
AB  - As the leading cause of cancer-related death among human beings, lung cancer
      seriously threats peoples' health all over the world. Cytokine-induced killer
      cells (CIK) is a new kind of adaptive immune cells characterized by its dramatic
      proliferation ability and cytotoxicity, non-major histocompatibility antigens
      (MHC) restriction and low side effects, which draw an increasing attention in
      recent years. The review is to introduce the basic features and mechanism of CIK
      cells briefly and summarize the researches of CIK cells used in the clinical
      therapy for lung cancer. Finally, we discuss several problems that should be
      addressed before CIK cells are widely applied to clinical patients.

PMID- 22152698
TI  - [Advances of DNA damage repair and Cisplatin resistance mechanisms in lung
      cancer].
AB  - Lung cancer is the most common cause of death from cancer worldwide per year.
      Platinum-based combination chemotherapy is a main treatment of lung cancer.
      Cisplatin is adopted widely and used effectively in the first-line chemotherapy.
      Unfortunately, development of cisplatin resistance is a major obstacle to the
      success of lung caner. Cisplatin is a cell-cycle-non-specific cytotoxic drugs and
      its main target is DNA. Thus, defective DNA damage repair is one of the main
      mechanisms of cisplatin resistance. In this review, we will focus on the
      defective DNA damage repair in cisplatin resistance of lung cancer including
      nucleotide excision repair, DNA mismatch repair, DNA double-strand break repair
      and translesion synthesis.

PMID- 22152699
TI  - The influence of a weight-bearing platform on the mechanical behavior of two
      Ilizarov ring fixators: tensioned wires vs. half-pins.
AB  - BACKGROUND: A weight-bearing platform applied at the distal end of an Ilizarov
      external frame allows patients with hindfoot transfixations, foot deformities or
      plantar skin lesions to bear weight. This leads to an indirect loading of the
      fracture or osteotomy site. However, the effect on the fracture/osteotomy site's
      motion or compressive loads is unknown. The aim of this study was to analyze the
      mechanical effects of a weight-bearing platform on the traditional all-wire, four
      ring frame in comparison to a two-ring frame consisting of half-pins. METHODS:
      Two frame configurations, with either anatomically positioned wires or half-pins,
      were analyzed with and without a weight-bearing platform applied underneath the
      distal ring. Composite tibiae with a mid-diaphyseal osteotomy of 3.5 mm were used
      in all the experiments. An axial load was applied with the use of a universal
      test machine (UTS(r)). Interfragmentary movements, the relative movements of bone
      fragments and movements between rings were recorded using displacement
      transducers. Compressive loads at the osteotomy site were recorded with loading
      cells. RESULTS: Indirect loading with a weight-bearing platform altered the force
      transmission through the osteotomy. Indirect loading of the tibiae decreased the
      extent of the axial micro-motion by 50% under the applied weight load when
      compared to direct weight loading (p < 0.05). The half pin frame was 25% stiffer
      than the wire frame under both direct and indirect loading of the tibiae (p <
      0.05). Compressive loads under indirect loading were reduced by 67% in the wire
      frame and by 57% in the half-pin frames compared to direct loading of the bones
      (p < 0.05). While axial loading in the wire frames resulted in plain axial
      movements at the site of the osteotomy, it was coupled with translational
      movements and angular displacements in the half pin mountings. This effect was
      more apparent in the case of indirect loading. CONCLUSIONS: A weight-bearing
      platform has substantial influence on the biomechanical performance of an
      Ilizarov external fixator. Half-pins induce greater stiffness to the Ilizarov
      external fixator and allow the usage of only one ring per bone segment, but shear
      stresses at the osteotomy under axial loading should be considered. The results
      allow an estimation of the size and direction of interfragmentary movements based
      on the extent of weight bearing.

PMID- 22152701
TI  - Understanding caregivers' attitudes towards physical punishment of children:
      evidence from 34 low- and middle-income countries.
AB  - OBJECTIVES: This article presents findings on caregivers' attitudes towards
      physical punishment of children from 34 household surveys conducted in low- and
      middle-income countries in 2005 and 2006. The article analyzes the variability in
      attitudes by background characteristics of the respondents to examine whether
      various factors at the individual and family levels correlate with the
      caregivers' beliefs in the need for violent discipline. The article also examines
      to what extent attitudes influence behaviors and compares groups of respondents
      to see how attitudes relate to disciplinary practices across caregivers of
      different socio-economic backgrounds. METHODS: The analysis is based on
      nationally representative data from 33 MICS and 1 DHS surveys. Questions on child
      discipline were addressed to the mother (or primary caregiver) of one randomly
      selected child aged 2-14 years in each household. The questionnaire asked whether
      any member of the household had used various violent and non-violent disciplinary
      practices with that child during the past month. Additionally, the interviewers
      asked the respondent if she believed that, in order to bring up that child
      properly, physical punishment was necessary. The sample included 166,635
      mothers/primary caregivers. RESULTS: The analysis shows that, in most countries,
      the majority of mothers/primary caregivers did not think there was a need for
      physical punishment. Overall, characteristics such as household wealth and size,
      educational level and age, as well as place of residence were significantly
      associated with caregivers' attitudes. The analysis confirms that beliefs
      influence disciplinary practices to a large degree: in all the countries but two,
      children were significantly more likely to experience physical punishment if
      their mothers/primary caregivers thought such punishment was needed. However,
      large proportions of children were found to be subject to physical punishment
      even if their mothers/primary caregivers did not consider this method necessary.
      This discrepancy between attitudes and behaviors is observed, although to
      different extents, in all the countries and across groups of mothers/primary
      caregivers with different levels of education and wealth. CONCLUSIONS: The data
      presented in this article are among the few resources available to help develop a
      more global understanding of caregivers' motivation in using violent discipline
      across a multitude of low- and middle-income countries. As such, the analysis of
      these data provides important insights for the development of effective
      strategies that will promote positive parenting practices. However, further data
      collection and analysis are needed to fully understand the reasons why physical
      punishment is used - even when caregivers do not think such method is necessary -
      opening the door for an even sharper programmatic response to change the
      practice.

PMID- 22152700
TI  - Facial nerve outcomes in functional vestibular schwannoma surgery: less than
      total tumour excision significantly improves results.
AB  - OBJECTIVES: To determine the implications of a functional approach to vestibular
      schwannoma surgery, with facial nerve function prioritised higher than total
      tumour excision. STUDY DESIGN: A case-control study in a tertiary referral
      neurotology clinic. PATIENTS: A 'functional' surgical group treated after April
      2007 (n = 44, mean cerebellopontine angle dimension 27 mm), and an 'excisional'
      surgical group matched for tumour size, treated from 1997 to April 2007 (n =
      115). INTERVENTION: Change to more functional surgical approach. MAIN OUTCOMES
      MEASURED:  PRIMARY OUTCOME: facial nerve status. Secondary outcome: tumour
      recurrence in less-than-total tumour excision. RESULTS: Facial nerve
      preservation: 77 per cent House-Brackmann grade I-II in functional group at 12
      months, versus 57 per cent grade I-II in excisional group (p = 0.027). Tumour
      recurrence: 1 per cent in total excision group, 2 per cent in near-total group
      and 40 per cent in sub-total group. CONCLUSION: A functional approach to
      vestibular schwannoma surgery improves facial nerve preservation outcomes and
      reduces the requirement for facial nerve rehabilitative interventions. Tumour
      recurrence rates are low in near-totally excised lesions but significant if only
      sub-total excision is achieved.

PMID- 22152702
TI  - Fish consumption does not prevent increase in waist circumference in European
      women and men.
AB  - Fish consumption is the major dietary source of EPA and DHA, which according to
      rodent experiments may reduce body fat mass and prevent obesity. However, human
      studies have suggested that fish consumption has no appreciable association with
      body-weight gain. We investigated the associations between fish consumption and
      subsequent change in waist circumference. Sex, age and waist circumference at
      enrolment were considered as potential effect modifiers. Women and men (n 89 432)
      participating in the European Prospective Investigation into Cancer and Nutrition
      (EPIC) were followed for a median of 5.5 years. Mixed-effect linear regression
      was used to investigate the associations between fish consumption and subsequent
      change in waist circumference. Among all participants, the average annual change
      in waist circumference was - 0.01 cm/10 g higher total fish consumption per d (95
      % CI - 0.01, 0.00) and - 0.01 cm/10 g higher fatty fish consumption per d (95 %
      CI - 0.02, - 0.01), after adjustment for potential confounders. Lean fish
      consumption was not associated with change in waist circumference. Adjustment for
      potential over- or underestimation of fish consumption measurements did not
      systematically change the observed associations, but the 95 % CI became slightly
      wider. The results in subgroups from analyses stratified by sex, age or waist
      circumference at enrolment were not systematically different. In conclusion, the
      present study suggests that fish consumption does not prevent increase in waist
      circumference.

PMID- 22152704
TI  - This special issue on fish immunology contains 19 reviews that summarize the most
      recent findings of the last 5-10 years of research in fish immunology.
      Introduction.

PMID- 22152703
TI  - Purchases of ready-to-eat cereals vary across US household sociodemographic
      categories according to nutritional value and advertising targets.
AB  - OBJECTIVE: To describe ready-to-eat (RTE) cereal purchases in 2008 in the USA
      according to cereal nutritional quality and marketing strategy and household
      sociodemographic characteristics. DESIGN: Cross-sectional study of purchases in
      one year. Each type of cereal was assigned to one of four nutrition quality
      categories (based on Nutrient Profile Index, NPI) and one of four advertising
      categories based on television exposure and analysis of packaging (child
      targeted, family-targeted, adult-targeted and no television advertising). Medians
      and distributions of purchase indicators were calculated for the cereal
      categories and the distributions were compared across sociodemographic groups.
      SETTING: RTE cereals (n 249) with complete label and nutritional content.
      SUBJECTS: RTE cereal purchases according to household sociodemographic
      characteristics obtained from Nielsen Homescan, a nationally representative panel
      of households. RESULTS: Purchases of RTE cereals were highest in households with
      one or more child and lowest in African-American and Asian households, as well as
      those earning <$US 30 000 per annum. The lowest-quality products were purchased
      by four times as many households as the highest-quality cereals, but loyalty to
      these products was lower. Purchases of cereals by households with children and in
      African-American and Hispanic households increased as cereal nutritional quality
      declined. Compared with non-advertised products, advertised child-targeted
      cereals were purchased thirteen times more frequently; family-targeted brand
      purchases were ten times higher; and adult-targeted cereals were purchased four
      times more frequently. CONCLUSIONS: Our findings suggest that improving the
      nutritional quality of RTE cereals with advertising targeted to children could
      also lead to increased consumption of healthier products by young people.

PMID- 22152705
TI  - Outbreak of NDM-1-producing Enterobacteriaceae in northern Italy, July to August
      2011.
AB  - Between July 2011 and August 2011, the New Delhi metallo-beta-lactamase 1 (NDM-1)
      gene was detected in Klebsiella pneumoniae and Escherichia coli isolates obtained
      from six patients hospitalised in four healthcare facilities in northern Italy.
      The patient who had been hospitalised in New Delhi, India, from February to May
      2011 and subsequently in the Bologna area, Italy, from May to July 2011, may have
      been the source of the outbreak. Our findings suggest ongoing spread of this
      carbapenem-resistance gene in Italy and highlight the need for intensive
      surveillance.

PMID- 22152706
TI  - National outbreak of Salmonella Java phage type 3b variant 9 infection using
      parallel case-control and case-case study designs, United Kingdom, July to
      October 2010.
AB  - Between July and October 2010, a national outbreak comprising 136 cases of
      Salmonella Java phage type 3b variant 9 was identified by the Health Protection
      Agency. Most cases were female. Cases had a median age of 39.5 years and lived in
      London, the South East and East of England. Parallel case-control and case-case
      study designs were undertaken to test the generated hypotheses. The case-case
      study aimed to examine if the infection was associated with eating food items
      purchased from commercial catering settings, and the reference group comprised
      non-travel related cases of S. Enteritidis infected during the same time period
      as the cases. The case-control study was designed to examine if the infection was
      associated with specific food items purchased from commercial catering settings,
      and recruited case-nominated controls. However, in response to poor recruitment
      we adapted our methods to investigate food exposures in the same way. Results of
      epidemiological investigations are compatible with salad vegetables as the
      potential source, but no common suppliers of salad were identified and no
      organisms were isolated from environmental and food samples. Limitations in the
      case-control study highlight the potential value of using a combination of
      epidemiological methods to investigate outbreaks.

PMID- 22152707
TI  - Streptococcus pyogenes cluster in a care home in England April to June 2010.
AB  - Two fatal cases of Streptococcus pyogenes emm st22.6 bacteraemia occurred in a
      care home in England during April and June 2010, initiating a cluster
      investigation. The first case had left the home 13 days before the second case
      took up residence. We sought further cases and carriers. We swabbed throat and
      chronic skin lesions from residents and staff and examined these specimens for
      the presence of S. pyogenes. 61 specimens were taken from 18 of 19 residents and
      39 of 39 staff. All results from swabbing were culture negative. We observed
      infection control practices and the environment at the care home for
      deficiencies. Issues were identified relating to the correct use of personal
      protective equipment, hand hygiene, clinical waste and laundry. Infection control
      practices were improved and training given. Infection control practices and the
      environment at a care home should be examined as part of the investigation of a
      S. pyogenes cluster. Screening for carriage of S. pyogenes should be done before
      antibiotic chemoprophylaxis is issued to care home residents and staff.

PMID- 22152708
TI  - The European Commission publishes call for proposals under the 2012  Ideas  work
      programme of the 7th Framework Programme.

PMID- 22152709
TI  - European Food Safety Authority evaluates public health risk of Shiga toxin
      producing Escherichia coli (STEC) in seeds and sprouted seeds.

PMID- 22152712
TI  - Spontaneous reattachment of Descemet stripping automated endothelial keratoplasty
      lenticles.

PMID- 22152714
TI  - Hemorrhage with anticoagulants and antiplatelets in vitreoretinal surgery.

PMID- 22152716
TI  - Facial nerve injury: a complication of superficial temporal artery biopsy.

PMID- 22152718
TI  - Risk factors for development of choroidal detachment after scleral buckling
      procedure.

PMID- 22152719
TI  - Clinical significance of microbial growth on the surfaces of silicone tubes
      removed from dacryocystorhinostomy patients.

PMID- 22152722
TI  - Severe brain atrophy after long-term survival seen in siblings with familial
      amyotrophic lateral sclerosis and a mutation in the optineurin gene: a case
      series.
AB  - INTRODUCTION: Previous studies have shown widespread multisystem degeneration in
      patients with sporadic amyotrophic lateral sclerosis who develop a total locked
      in state and survive under mechanical ventilation for a prolonged period of time.
      However, the disease progressions reported in these studies were several years
      after disease onset. There have been no reports of long-term follow-up with brain
      imaging of patients with familial amyotrophic lateral sclerosis at an advanced
      stage of the disease. We report the cases of siblings with amyotrophic lateral
      sclerosis with homozygous deletions of the exon 5 mutation of the gene encoding
      optineurin, in whom brain computed tomography scans were followed up for more
      than 20 years. CASE PRESENTATION: The patients were a Japanese brother and
      sister. The elder sister was 33 years of age at the onset of disease, which began
      with muscle weakness of her left lower limb. Two years later she required
      mechanical ventilation. She became bedridden at the age of 34, and died at the
      age of 57. A computed tomography scan of her brain at the age of 36 revealed no
      abnormality. Atrophy of her brain gradually progressed. Ten years after the onset
      of mechanical ventilation, atrophy of her whole brain, including the cerebral
      cortex, brain stem and cerebellum, markedly progressed. Her younger brother was
      36 years of age at the onset of disease, which presented as muscle weakness of
      his left upper limb. One year later, he showed dysphagia and dysarthria, and
      tracheostomy ventilation was performed. He became bedridden at the age of 37 and
      died at the age of 55. There were no abnormal intracranial findings on brain
      computed tomography scans obtained at the age of 37 years. At the age of 48
      years, computed tomography scans showed marked brain atrophy with ventricular
      dilatation. Subsequently, atrophy of the whole brain rapidly progressed as in his
      elder sister. CONCLUSION: We conclude that a homozygous deletion-type mutation in
      the optineurin gene may be associated with widespread multisystem degeneration in
      amyotrophic lateral sclerosis.

PMID- 22152724
TI  - An Hcp100 gene fragment reveals Histoplasma capsulatum presence in lungs of
      Tadarida brasiliensis migratory bats.
AB  - Histoplasma capsulatum was sampled in lungs from 87 migratory Tadarida
      brasiliensis bats captured in Mexico (n=66) and Argentina (n=21). The fungus was
      screened by nested-PCR using a sensitive and specific Hcp100 gene fragment. This
      molecular marker was detected in 81.6% [95% confidence interval (CI) 73.4-89.7]
      of all bats, representing 71 amplified bat lung DNA samples. Data showed a T.
      brasiliensis infection rate of 78.8% (95% CI 68.9-88.7) in bats captured in
      Mexico and of 90.4% (95% CI 75.2-100) in those captured in Argentina. Similarity
      with the H. capsulatum sequence of a reference strain (G-217B) was observed in 71
      Hcp100 sequences, which supports the fungal findings. Based on the neighbour
      joining and maximum parsimony Hcp100 sequence analyses, a high level of
      similarity was found in most Mexican and all Argentinean bat lung samples.
      Despite the fact that 81.6% of the infections were molecularly evidenced, only
      three H. capsulatum isolates were cultured from all samples tested, suggesting a
      low fungal burden in lung tissues that did not favour fungal isolation. This
      study also highlighted the importance of using different tools for the
      understanding of histoplasmosis epidemiology, since it supports the presence of
      H. capsulatum in T. brasiliensis migratory bats from Mexico and Argentina, thus
      contributing new evidence to the knowledge of the environmental distribution of
      this fungus in the Americas.

PMID- 22152723
TI  - Sustained remission of symptoms and improved health-related quality of life in
      patients with cryopyrin-associated periodic syndrome treated with canakinumab:
      results of a double-blind placebo-controlled randomized withdrawal study.
AB  - INTRODUCTION: To assess the effect of canakinumab, a fully human anti-interleukin
      1beta antibody, on symptoms and health-related quality of life (HRQoL) in
      patients with cryopyrin-associated periodic syndrome (CAPS). METHODS: In this 48
      week, phase 3 study, patients with CAPS received canakinumab 150 mg
      subcutaneously at 8-week intervals. All patients (n = 35) received canakinumab
      during weeks 1 through 8; weeks 9 through 24 constituted a double-blind placebo
      controlled withdrawal phase, and weeks 24 through 48 constituted an open-label
      phase in which all patients received canakinumab. Patient and physician
      assessments of symptoms, levels of inflammatory markers, and HRQoL were
      performed. RESULTS: Rapid symptom remission was achieved, with 89% of patients
      having no or minimal disease activity on day 8. Responses were sustained in
      patients receiving 8-weekly canakinumab. Responses were lost during the placebo
      controlled phase in the placebo group and were regained on resuming canakinumab
      therapy in the open-label phase. Clinical responses were accompanied by decreases
      in serum levels of C-reactive protein, serum amyloid A protein, and interleukin
      6. HRQoL scores at baseline were considerably below those of the general
      population. Improvements in all 36-item Short-Form Health Survey (SF-36) domain
      scores were evident by day 8. Scores approached or exceeded those of the general
      U.S. population by week 8 and remained stable during canakinumab therapy.
      Improvements in bodily pain and role-physical were particularly marked,
      increasing by more than 25 points from baseline to week 8. Therapy was generally
      well tolerated. CONCLUSIONS: Canakinumab, 150 mg, 8-weekly, induced rapid and
      sustained remission of symptoms in patients with CAPS, accompanied by substantial
      improvements in HRQoL. TRIAL REGISTRATION: Clintrials.gov NCT00465985.

PMID- 22152725
TI  - Helmet noninvasive mechanical ventilation in patients with acute postoperative
      respiratory failure.
AB  - BACKGROUND: The physiological and clinical effects of noninvasive ventilation
      (NIV) on acute postoperative respiratory failure are relatively unknown. The aim
      of this study was to determine the prediction factors for failure in the use of
      NIV with a helmet in this context. METHODS: This was a prospective observational
      study. The use of NIV was assessed for a period of 2 years in a postoperative
      ICU. Demographic data were collected, as well as acute respiratory failure (ARF)
      and arterial gas readings. Hemodynamic changes were assessed using pulse contour
      cardiac output  technology, and the clinical development of subjects was
      recorded. All subjects who developed ARF were treated using NIV as their primary
      care, depending on whether the technique was successful or the subject required
      intubation. The risk factors that determined failure in the application  of NIV
      were subsequently determined. RESULTS: Of the 99 subjects presenting with
      postoperative ARF treated with NIV using a helmet, 74 did not require intubation
      (74.7%). Following a multivariate analysis using logistic regression, we
      determined that there are 3 independent risk factors for  the failure of NIV.
      Three factors were associated with respiratory failure: ARDS, pneumonia, and lack
      of improvement with NIV in 1 hour (increase in the P(aO(2))/F(IO(2))).
      CONCLUSIONS: NIV using a helmet could provide an effective alternative to
      conventional  ventilation in selected patients with postoperative ARF.

PMID- 22152727
TI  - Prescribing safety: the case of inappropriate medicines.

PMID- 22152728
TI  - Acute infective conjunctivitis in primary care: who needs antibiotics? An
      individual patient data meta-analysis.
AB  - BACKGROUND: Acute infective conjunctivitis is a common problem in primary care,
      traditionally managed with topical antibiotics. A number of clinical trials have
      questioned the benefit of topical antibiotics for patients with acute infective
      conjunctivitis. AIM: To determine the benefit of antibiotics for the treatment of
      acute infective conjunctivitis in primary care and which subgroups benefit most.
      DESIGN: An individual patient data meta-analysis. METHOD: Relevant trials were
      identified and individual patient data gathered for meta-analysis and subgroup
      analysis. RESULTS: Three eligible trials were identified. Individual patient data
      were available from all primary care trials and data were available for analysis
      in 622 patients. Eighty per cent (246/308) of patients who received antibiotics
      and 74% (233/314) of controls were cured at day 7. There was a significant
      benefit of antibiotics versus control for cure at seven days in all cases
      combined (risk difference 0.08, 95% confidence interval (CI) = 0.01 to 0.14).
      Subgroups that showed a significant benefit from antibiotics were patients with
      purulent discharge (risk difference 0.09, 95% CI = 0.01 to 0.17) and patients
      with mild severity of red eye (risk difference 0.10, 95% CI = 0.02 to 0.18),
      while the type of control used (placebo drops versus nothing) showed a
      statistically significant interaction (P=0.03). CONCLUSION: Acute conjunctivitis
      seen in primary care can be thought of as a self-limiting condition, with most
      patients getting better regardless of antibiotic therapy. Patients with purulent
      discharge or a mild severity of red eye may have a small benefit from
      antibiotics. Prescribing practices need to be updated, taking into account these
      results.

PMID- 22152729
TI  - Measuring blood pressure in primary care: identifying 'white coat syndrome' and
      blood pressure device comparison.

PMID- 22152730
TI  - Caring for migrant patients in the UK: how the Migrant Health Guide can help.

PMID- 22152731
TI  - Revised guidelines for cardiovascular risk management.

PMID- 22152732
TI  - The QOF, NICE, and depression.

PMID- 22152733
TI  - GPs at the Deep End and Mike Fitzpatrick.

PMID- 22152734
TI  - Influence of patient payment on antibiotic prescribing in Irish general practice:
      a cohort study.
AB  - BACKGROUND: Antibiotics are widely believed to be overused and misused.
      Approximately 80% of all prescriptions for antibiotics are written by GPs. There
      are many external factors that influence a GP's decision to prescribe, including
      patient pressure. Access to primary care services operates on a two-tier system
      in the Republic of Ireland: General Medical Service (GMS) card holders have free
      access to GPs and medications; and non-card holders (private patients) must pay a
      non-subsidised fee to visit their GP. AIM: To ascertain whether there was a
      difference in antibiotic prescribing practice between those who pay a fee for
      their GP consultation and those who attend free of charge. DESIGN AND SETTING:
      Cohort study in Irish general practice. METHOD: All GPs attending continuing
      medical education (CME) groups nationwide were invited to participate from
      October 2008 until April 2010. GPs gathered data on 100 consecutive consultations
      including diagnosis and patient characteristics. RESULTS: Data were collected
      from 171 GPs (distributed throughout Ireland), which resulted in 16 899
      consultations. Antibiotics were prescribed at 3407 (20.16%) consultations. Nearly
      half of the prescriptions were for GMS card holders (n = 1669; 48.99%) and 1526
      (44.79%) were for private patients; for 212 (6.22%) the payment status of the
      patient was unknown. Private patients were more likely to receive a prescription
      for antibiotics (odds ratio 1.23, 95% confidence interval = 1.14 to 1.33).
      CONCLUSION: These results demonstrate that a GP's decision to provide a
      prescription for antibiotics may be influenced by whether or not the patient pays
      for their consultation at the GP interface. Private patients are more likely than
      GMS card holders to receive a prescription for antibiotics.

PMID- 22152735
TI  - Correlation between prescribing quality and pharmaceutical costs in English
      primary care: national cross-sectional analysis.
AB  - BACKGROUND: Both pharmaceutical costs and quality-indicator performance vary
      substantially between general practices, but little is known about the
      relationship between prescribing costs and quality. AIM: To measure the
      association between prescribing quality and pharmaceutical costs among English
      general practices. DESIGN AND SETTING: Cross-sectional observational study using
      data from the Quality and Outcomes Framework and the Prescribing Analysis and
      Cost database from all 8409 general practices in England in 2005-2006. METHOD:
      Correlation between practice achievement of 26 prescribing quality indicators in
      eight prescribing areas and related pharmaceutical costs was examined. RESULTS:
      There was no significant association between the overall achievement of quality
      indicators and related pharmaceutical costs (P= 0.399). Mean achievement of
      quality indicators across all eight prescribing areas was 79.0% (standard
      deviation 4.4%). There were small positive correlations in five prescribing
      areas: influenza vaccination, beta blockers, angiotensin converting enzyme
      inhibitors, lipid lowering, and antiplatelet treatment (all P<0.001). There were
      small negative correlations in two prescribing areas: hypertension (P<0.001) and
      smoking cessation (P = 0.018). CONCLUSION: Correlations between prescribing
      quality and pharmaceutical costs were much smaller than expected; possible
      explanations for this include a substantial variation in rates of prescribing
      outside evidence-based protocols, and use of expensive pharmaceuticals instead of
      cheaper effective alternatives. There remains considerable scope for some
      practices to make pharmaceutical cost savings while improving quality
      performance. The ratio of quality scores to related pharmaceutical costs could be
      developed into a performance indicator.

PMID- 22152736
TI  - Trends in primary care antidepressant prescribing 1995-2007: a longitudinal
      population database analysis.
AB  - BACKGROUND: Antidepressant prescribing is increasing worldwide, prompting policy
      interventions and targets to halt the rise. AIM: To examine time trends in GP
      antidepressant prescribing using patient-level data. DESIGN AND SETTING:
      Longitudinal population database of all community pharmacy dispensed
      prescriptions for all 325,000 residents of the Tayside region of Scotland.
      METHOD: In each of 3 study years (1995/1996, 2000/2001 and 2006/2007), the volume
      of antidepressants prescribed was calculated, and numbers of patients prescribed
      antidepressants in each year, mean treatment duration, and mean dose per patient
      in that year examined using descriptive statistics. RESULTS: Total drug volume
      increased threefold between 1995/1996 and 2006/2007, largely driven by increases
      in selective serotonin reuptake inhibitor (SSRI) prescribing, and laterally also
      in 'other' antidepressant prescribing. Tricyclic prescribing is static, but low
      dose amitriptyline increasingly dominates this drug class. Increased drug volume
      was initially driven by increasing patient numbers (from 8.0% of the population
      prescribed at least once in 1995/1996 to 11.9% in 2000/2001) and increased
      treatment duration (from 170 days in the measurement year to 200). Latterly, drug
      volume increases are increasingly attributable to longer duration of treatment
      and higher mean daily dose. CONCLUSION: The large rise in antidepressant volumes
      is caused by a complex mixture of more patients being prescribed SSRI and 'other'
      antidepressants, the use of higher doses, and longer durations of treatment, with
      the balance changing overtime. Tricyclic prescribing is now largely low dose, and
      probably for conditions other than depression. Interventions to improve the
      quality of antidepressant prescribing need to be more subtle than blanket targets
      to reduce the total volume of antidepressants prescribed.

PMID- 22152738
TI  - Time to make a difference.

PMID- 22152740
TI  - Minimal interventions to decrease long-term use of benzodiazepines in primary
      care: a systematic review and meta-analysis.
AB  - BACKGROUND: Long-term use of benzodiazepines (BZDs) is common. Not only is such
      use ineffective, but it also has several risks in addition to dependence, and
      remains a significant problem among the older population. AIM: To systematically
      review randomised controlled trials that evaluate the effectiveness of minimal
      interventions to reduce the long-term use of BZDs in primary care. DESIGN AND
      SETTING: Systematic review and meta-analysis of randomised controlled trials in
      UK general practices. METHOD: Cochrane Central, MEDLINE, and Embase (1967-2010)
      were searched for trials of minimal interventions (such as a single letter or one
      consultation from a GP) for patients in primary care with long-term (>3 months)
      BZD use. Pooled risk differences were calculated with 95% confidence intervals.
      RESULTS: From 646 potentially relevant abstracts, three studies (615 patients)
      met all the inclusion criteria. The pooled risk ratio showed a significant
      reduction/cessation in BZD consumption in the minimal intervention groups
      compared to usual care (risk ratio [RR] = 2.04, 95% confidence interval [CI] =
      1.5 to 2.8, [corrected] P<0.001; RR = 2.4, 95% CI = 1.3 to 4.3, P = 0.008)
      respectively. Two studies also reported a significant proportional reduction in
      consumption of BZD from baseline to 6 months in intervention groups compared to
      the control group. The secondary outcome of general health status was measured in
      two studies; both showed a significant improvement in the intervention group.
      CONCLUSION: A brief intervention in the form of either a letter or a single
      consultation by GPs, for long-term users of BZD, is an effective and efficient
      strategy to decrease or stop their medication, without causing adverse
      consequences.

PMID- 22152741
TI  - Why Amy was right about rehab.

PMID- 22152742
TI  - Characteristics of patients who consult their GP on their birthdays.

PMID- 22152743
TI  - Generation Y.

PMID- 22152744
TI  - The NHS reforms: what they will mean for generalist and specialist clinicians.

PMID- 22152745
TI  - Managing self-limiting respiratory tract infections: a qualitative study of the
      usefulness of the delayed prescribing strategy.
AB  - BACKGROUND: Despite respiratory tract infections usually being viral and self
      limiting, most primary care consultations still result in an antibiotic
      prescription. The National Institute for Health and Clinical Excellence (NICE)
      introduced the 'delayed prescribing' (DP) strategy. It remains unknown how useful
      UK clinicians find this approach. AIM: To investigate how DP is used within UK
      primary care, and the benefits and challenges associated with this strategy.
      DESIGN AND SETTING: Qualitative interview and focus group study in UK scheduled
      and unscheduled care primary care settings. METHOD: Data were gathered through
      semi-structured interviews (n = 49) and six focus groups with GPs, trainee GPs,
      and nurse prescribers (NPs). An iterative analysis approach, using grounded
      theory principles, was used to generate themes from the dataset. RESULTS:
      Prescribers were familiar with DP but used it infrequently. DP was often used to
      manage diagnostic uncertainty, although NPs, trainee GPs, and GPs working in
      unscheduled care services preferred patients to reconsult under these
      circumstances. Prescribers used DP to avoid conflict, although some had found
      more effective strategies to achieve this. Prescribers were generally
      uncomfortable giving clinical responsibility to patients, and DP was perceived to
      communicate a conflicting message to patients about antibiotic efficacy.
      CONCLUSION: DP was not considered to be a helpful strategy for managing patients
      with self-limiting respiratory tract infections within primary care and the
      findings do not support the centrality of DP in NICE guidelines as a primary
      means of reducing antibiotic prescribing. Future training and guidelines should
      encourage alternative ways of communicating empathy, addressing patient beliefs,
      and encouraging self-management.

PMID- 22152746
TI  - Irreversible visual loss secondary to excessive topical steroid use in eczema.

PMID- 22152747
TI  - Tips for GP trainees working in ophthalmology.

PMID- 22152748
TI  - Thirty-minute compared to standardised office blood pressure measurement in
      general practice.
AB  - BACKGROUND: Although blood pressure measurement is one of the most frequently
      performed measurements in clinical practice, there are concerns about its
      reliability. Serial, automated oscillometric blood pressure measurement has the
      potential to reduce measurement bias and white-coat effect'. AIM: To study
      agreement of 30-minute office blood pressure measurement (OBPM) with standardised
      OBPM, and to compare repeatability. DESIGN AND SETTING: Method comparison study
      in two general practices in The Netherlands. METHOD: Thirty-minute and
      standardised OBPM was carried out with the same, validated device in 83 adult
      patients, and the procedure was repeated after 2 weeks. During 30-minute OBPM,
      blood pressure was measured automatically every 3 minutes, with the patient in a
      sitting position, alone in a quiet room. Agreement between 30-minute and
      standardised OBPM was assessed by Bland-Altman analysis. Repeatability of the
      blood pressure measurement methods after 2 weeks was expressed as the mean
      difference in combination with the standard deviation of difference (SDD).
      RESULTS: Mean 30-minute OBPM readings were 7.6/2.5 mmHg (95% confidence interval
      [CI] = 6.1 to 9.1/1.5 to 3.4 mmHg) lower than standardised OBPM readings. The
      mean difference and SDD between repeated 30-minute OBPMs (mean difference = 3/1
      mmHg, 95% CI = 1 to 5/0 to 2 mmHg; SDD 9.5/5.3 mmHg) were lower than those of
      standardised OBPMs (mean difference = 6/2 mmHg, 95% CI = 4 to 8/1 to 4 mmHg; SDD
      10.9/6.3 mmHg). CONCLUSION: Thirty-minute OBPM resulted in lower readings than
      standardised OBPM and had a better repeatability. These results suggest that 30
      minute OBPM better reflects the patient's true blood pressure than standardised
      OBPM does.

PMID- 22152749
TI  - Type and accuracy of sphygmomanometers in primary care: a cross-sectional
      observational study.
AB  - BACKGROUND: Previous studies identified worrying levels of sphygmomanometer
      inaccuracy and have not been repeated in the era of digital measurement of blood
      pressure. AIM: To establish the type and accuracy of sphygmomanometers in current
      use. DESIGN AND SETTING: Cross-sectional, observational study in 38 Oxfordshire
      primary care practices. METHOD: Sphygmomanometers were evaluated between 50 and
      250 mmHg, using Omron PA350 or Scandmed 950831-2 pressure meters. RESULTS: Six
      hundred and four sphygmomanometers were identified: 323 digital (53%), 192
      aneroid (32%), 79 mercury (13%), and 10 hybrid (2%) devices. Of these, 584 (97%)
      could be fully tested. Overall, 503/584 (86%) were within 3 mmHg of the
      reference, 77/584 (13%) had one or more error of 4-9 mmHg, and 4/584 (<1%) had
      one or more error of more than 10 mmHg. Mercury (71/75, 95%) and digital
      (272/308, 88%) devices were more likely to be within 3 mmHg of the reference
      standard than aneroid models (150/191, 78%) (Fisher's exact test P = 0.001).
      Donated aneroid devices from the pharmaceutical industry performed significantly
      worse: 10/23 (43%) within 3 mmHg of standard compared to 140/168 (83%) aneroid
      models from recognised manufacturers (Fisher's exact test P<0.001). No
      significant difference was found in performance between manufacturers within each
      device type, for either aneroid (Fisher's exact test P = 0.96) or digital
      (Fisher's exact test P = 0.7) devices. CONCLUSION: Digital sphygmomanometers have
      largely replaced mercury models in primary care and have equivalent accuracy.
      Aneroid devices have higher failure rates than other device types; this appears
      to be largely accounted for by models from indiscernible manufacturers. Given the
      availability of inexpensive and accurate digital models, GPs could consider
      replacing aneroid devices with digital equivalents, especially for home visiting.

PMID- 22152750
TI  - Stroke patients' perceptions of home blood pressure monitoring: a qualitative
      study.
AB  - BACKGROUND: Stroke is the leading cause of adult disability in the UK.
      Hypertension is the leading modifiable risk factor for stroke. There is
      increasing interest n home blood pressure monitors for self-monitoring, but no
      published research on the experiences of stroke patients who do self-monitor.
      AIM: To explore stroke patients' experiences of self-monitoring with nurse-led
      support. DESIGN AND SETTING: A qualitative study of 26 (66%) patients from the
      first 39 participants to complete the intervention arm of a community-based
      randomised controlled trial (RCT) of home blood pressure monitoring in 381
      patients recruited from hospital stroke clinics in south London. METHOD: Semi
      structured face-to-face interviews were conducted with 26 patients. Interviews
      were digitally recorded and transcribed, and a thematic analysis of the data was
      undertaken. RESULTS: Participants were highly motivated to avoid a further stroke
      and developed a strong focus on blood pressure control and attaining a 'good
      result'. Only a minority reported anxiety about their blood pressure.
      Participants gained a welcome sense of empowerment and control over managing
      their health; some felt confident and 'experimented' with their medication doses.
      Eight patients required physical help to self-monitor and there was uncertainty
      about where responsibility lay for such help. Patients who lived alone and were
      functionally impaired had the least positive experience. Active engagement with
      the home blood pressure monitoring process by GPs was variable. CONCLUSION:
      Patients in this study generally reported increased knowledge and empowerment
      about blood pressure control and avoiding further strokes. The technique is
      overall welcome, acceptable, and successful, even in patients with disabilities.
      Since home blood pressure monitoring can also lead to improved blood pressure
      control, this simple, pragmatic intervention might be more widely used.

PMID- 22152751
TI  - Lapatinib and trastuzumab in combination with an aromatase inhibitor for the
      first-line treatment of metastatic hormone receptor-positive breast cancer which
      over-expresses human epidermal growth factor 2 (HER2): a systematic review and
      economic analysis.
AB  - BACKGROUND: Breast cancer is the uncontrolled, abnormal growth of malignant
      breast tissue affecting predominantly women. Metastatic breast cancer (mBC) is an
      advanced stage of the disease when the disease has spread beyond the original
      organ. Hormone receptor status and human epidermal growth factor 2 (HER2) status
      are two predictive factors that are taken into consideration when estimating the
      prognosis of patients with breast cancer. OBJECTIVES: To review the clinical
      effectiveness and cost-effectiveness evidence base for lapatinib (LAP) in
      combination with an aromatase inhibitor (AI) and trastuzumab (TRA) in combination
      with an AI for the first-line treatment of patients who have hormone receptor
      positive (HR+)/human epidermal growth factor 2-positive (HER2+) mBC. DATA
      SOURCES: Relevant electronic databases and websites, including MEDLINE, EMBASE
      and the Cochrane Library, were searched until May 2010. Further data were derived
      from the manufacturers' submissions for LAP + AI and TRA + AI. REVIEW METHODS: A
      systematic review of the clinical effectiveness and cost-effectiveness of LAP +
      AI and TRA + AI was undertaken. As it was deemed inappropriate to compare LAP +
      AI with TRA + AI, two separate assessments of cost-effectiveness versus AIs alone
      were undertaken. RESULTS: Three trials were included in the systematic review
      [the patient populations of the efficacy and safety of lapatinib combined with
      letrozole (EGF30008) trial, the efficacy and safety of trastuzumab combined with
      anastrozole (TAnDEM) trial and the efficacy and safety of letrozole combined with
      trastuzumab (eLEcTRA) trial]. As a result of differences in the exclusion
      criteria and because one trial was halted prematurely, comparisons across trials
      were believed to be inappropriate and meta-analysis was not possible.
      Individually, however, the findings from the trials all suggest that LAP + AI or
      TRA + AI results in improved progression-free survival and/or time to progression
      when compared with AIs alone. The trials do not show a statistically significant
      benefit in terms of overall survival. Two separate economic analyses were
      conducted based on the completed trials; neither LAP + AI nor TRA + AI was found
      to be cost-effective when compared with AI monotherapy. LIMITATIONS: Because of
      differences in the EGF30008 and the TAnDEM trials, the Assessment Group believes
      the indirect comparisons analyses conducted by the manufacturers are
      inappropriate and, for the same reason, chooses not to compare LAP + AI with TRA
      + AI in an economic evaluation. CONCLUSIONS: LAP + AI and TRA + AI appear to be
      clinically more effective than AI monotherapy, but neither is cost-effective
      compared with AIs alone. It was not possible to compare LAP + AI with TRA + AI.
      Future research should include research into treating mBC in the HR+/HER2+
      population who are not TRA (or LAP) naive and into comparing the clinical
      effectiveness of AIs as monotherapy in patients with HER2+ and human epidermal
      growth factor 2-negative breast cancer. FUNDING: The National Institute for
      Health Research Technology Assessment programme.

PMID- 22152752
TI  - The Intelligent Ventilator (INVENT) project: the role of mathematical models in
      translating physiological knowledge into clinical practice.
AB  - This dissertation has addressed the broad hypothesis as to whether building
      mathematical models is useful as a tool for translating physiological knowledge
      into clinical practice. In doing so it describes work on the INtelligent
      VENTilator project (INVENT), the goal of which is to build, evaluate and
      integrate into clinical practice, a model-based decision support system for
      control of mechanical ventilation. The dissertation describes the mathematical
      models included in INVENT, i.e. a model of pulmonary gas exchange focusing on
      oxygen transport, and a model of the acid-base status of blood, interstitial
      fluid and tissues. These models have been validated, and applied in two other
      systems: ALPE, a system for measuring pulmonary gas exchange and ARTY, a system
      for arterialisation of the acid-base and oxygen status of peripheral venous
      blood. The major contributions of this work are as follows. A mathematical model
      has been developed which can describe pulmonary gas exchange more accurately that
      current clinical techniques. This model is parsimonious in that it can describe
      pulmonary gas exchange from measurements easily available in the clinic, along
      with a readily automatable variation in F(I)O(2). This technique and model have
      been developed into a research and commercial tool (ALPE), and evaluated both in
      the clinical setting and when compared to the reference multiple inert gas
      elimination technique (MIGET). Mathematical models have been developed of the
      acid- base chemistry of blood, interstitial fluid and tissues, with these models
      formulated using a mass-action mass-balance approach. The model of blood has been
      validated against literature data describing the addition and removal of CO(2),
      strong acid or base, and haemoglobin; and the effects of oxygenation or
      deoxygenation. The model has also been validated in new studies, and shown to
      simulate accurately and precisely the mixing of blood samples at different PCO(2)
      and PO(2) levels. This model of acid-base chemistry of blood has been applied in
      the ARTY system. ARTY has been shown to accurately and precisely calculate
      arterial values of acid-base and oxygen status in patients residing in the ICU,
      and in those with chronic lung disease. The INtelligent VENTilator (INVENT)
      system has been developed for optimization of mechanical ventilator settings
      using physiological models and utility/penalty functions, separating
      physiological knowledge from clinical preference. The models can be tuned to the
      individual patient via parameter estimation, providing patient specific advice.
      The INVENT team has shown prospectively that the system provides advice on
      F(I)O(2) which is as good as clinical practice, and retrospectively that the
      system provides reasonable suggestions of tidal volume, respiratory frequency and
      F(I)O(2). In general, this dissertation has illustrated a further example of the
      role of modeling in describing and understanding complex systems. The
      dissertation has shown that when dealing with complexity the goal of the model
      must be in focus if a correct balance is to be maintained between system
      complexity and model parameterization. The original goal of the INVENT team, i.e.
      to build, evaluate and integrate a DSS for control of mechanical ventilation has
      not as yet been completed. However, the broader hypothesis that building models
      generates new and interesting questions has been successfully demonstrated. The
      ALPE model and system has been applied in intensive care, post operative care and
      cardiology and is currently being evaluated in new clinical domains. ARTY has
      been shown to have potential benefit in eliminating the need for painful arterial
      punctures, and may also be useful as a screening tool. These systems illustrate
      the benefits of investing in models as a mechanism for translating physiological
      knowledge to clinical practice.

PMID- 22152755
TI  - Taking steps to control costs in the OR.
AB  - Hospitals continue to be challenged by rising expenses in an environment of
      moderate reimbursements. Health care costs have increasingly come under scrutiny
      and, with the advent of health care reform, will continue to be scrutinized.
      Perioperative nurses play a key role in evaluating product safety, effectiveness
      and efficiency, environmental concerns, and cost and how these factors affect
      patient care. Cost-saving opportunities that a hospital product evaluation
      committee can consider include choosing less expensive but equivalent supplies,
      comparing the expenses associated with disposable versus reusable products,
      limiting the use of custom supplies, determining ways to reduce linen use, and
      changing practices to eliminate products that are found to have little clinical
      value. Adopting effective product evaluation and purchasing practices can lead to
      reduced costs without affecting the quality of patient care.

PMID- 22152756
TI  - Selecting products safely.
AB  - With a focus on multiple stakeholders working together, AORN's "Recommended
      practices for product selection in perioperative practice settings" provides a
      source of information to help facilities choose safe and efficient perioperative
      products, including medical devices and other products used in the perioperative
      settings.

PMID- 22152757
TI  - Penis auto-amputation and chasm of the lower abdominal wall due to advanced
      penile carcinoma: a case report.
AB  - INTRODUCTION: Penile cancer is uncommon. When penile cancer is left untreated, at
      an advanced stage it can have tragic consequences for the patient. CASE
      PRESENTATION: Our case report does not concern a new manifestation of penile
      cancer, but an interesting presentation with clinical significance that
      emphasizes the need to diagnose and treat penile cancer early. It is an unusual
      case of a neglected penile cancer in a 57-year-old Greek man that led to auto
      amputation of the penis and a large chasm in the lower abdominal wall. The
      clinical staging was T4N3M0 and our patient was treated with a bilateral
      cutaneous ureterostomy, chemotherapy and radiotherapy. Our patient died 18 months
      after his first admission in our clinic. CONCLUSIONS: Emphasis must be placed on
      early diagnosis and treatment of penile cancer, so further development of the
      disease can be prevented.

PMID- 22152758
TI  - An unusual otoscopic finding associated with a type II first branchial cleft
      anomaly.
AB  - OBJECTIVE: We report an interesting case involving a child with a branchial cleft
      anomaly with two fistulous tracts, one of which was associated with an unusual
      otoscopic finding. CASE REPORT: A seven-year-old girl presented with an apparent
      type II first branchial cleft cyst after an acute infection. Parotidectomy and
      excision of the tract were performed, with subsequent development of pre
      auricular swelling three months later. Further surgery was performed to remove a
      second duplication anomaly of the external auditory canal. Otomicroscopy showed a
      fibrous band arising from the wall of the canal and attached to the tympanic
      membrane at the umbo. CONCLUSION: Otoscopic findings on physical examination can
      be important diagnostic clues in the early recognition of branchial cleft
      anomalies. The classification system proposed by Work may fail to describe some
      branchial cleft lesions.

PMID- 22152759
TI  - A long-term study assessing the factors influencing survival and morbidity in the
      surgical management of bronchiectasis.
AB  - BACKGROUND: Although the prevalence of bronchiectasis decreased significantly in
      developed countries, in less developed and in developing countries, it still
      represents a significant cause of morbidity and mortality. The aim of this
      retrospective study is to present our surgical experiences, the morbidity and
      mortality rates and outcome of surgical treatment for bronchiectasis. METHODS: We
      reviewed the medical records of 129 patients who underwent surgical resection for
      bronchiectasis between April 2002 and April 2010, at Van Training and Research
      Hospital, Thoracic Surgery Department. Variables of age, sex, symptoms, etiology,
      and surgical procedures, mortality, morbidity and the result of surgical therapy
      were analyzed retrospectively. RESULTS: Mean age was 21.8 year (the eldest was 67
      year, the youngest was 4 years-old). Male/female ratio was 1.86 and 75% of all
      patients were young population under the age of 40. Bilateral involvement was
      14.7%, left/right side ratio according to localization was 2.1/1. The most common
      reason for bronchiectasis was recurrent infection. Surgical indications were as
      follows: recurrent infection (54%), hemoptysis (35%), empyema (6%), and lung
      abscess (5%). There was no operative mortality. Complications occurred in 29
      patients and the morbidity rate was 22.4%. Complete resection was achieved in 110
      (85.2%) patients. Follow-up data were obtained for 123 (95%) of the patients. One
      patient died during follow-up. The mean follow-up of this patient was 9 months.
      Mean postoperative hospitalization time was 9.15 +/- 6.25 days. Significantly
      better results were obtained in patients who had undergone a complete resection.
      CONCLUSIONS: Surgical treatment of bronchiectasis can be performed with
      acceptable morbidity and mortality at any age. The involved bronchiectatic sites
      should be resected completely for the optimum control of symptoms.

PMID- 22152760
TI  - Household food insecurity and hunger among households in Sidama district,
      southern Ethiopia.
AB  - OBJECTIVE: To examine household food insecurity and hunger in Sidama Zone, one of
      the most populous zones in southern Ethiopia. DESIGN: Cross-sectional survey
      administered individually by trained interviewers. Food insecurity was calculated
      with both the Household Food Insecurity Access Scale (HFIAS) and the Household
      Hunger Scale (HHS), developed by the Food and Nutrition Technical Assistance
      Project. SETTING: Rural households from ten kebeles (the smallest administrative
      district) selected from two agro-climatic zones in Sidama, southern Ethiopia,
      from December 2010 to January 2011. SUBJECTS: Men and women respondents from 1094
      rural households were selected using multistage sampling techniques. RESULTS:
      Using the HFIAS, 17.7 % of households were food secure. The percentage of
      households that were mildly, moderately and severely food insecure was 6.8 %,
      27.7 % and 47.8 %, respectively. Using the HHS, 29.0 % and 5.6 % of households
      fell into the moderate and severe household hunger categories. Using multivariate
      statistical techniques, five variables were significant predictors of both food
      insecurity and hunger. These variables were migration of a household member, agro
      climatic zone, and younger age, less education and lower radio access for the
      woman. Being eligible for safety-net credit programmes also was a predictor of
      hunger, while limited animal ownership and household wealth as well as alcohol
      use by the household head added to the prediction of food insecurity.
      CONCLUSIONS: The study documented that food insecurity is a major concern of
      smallholder farming households in the study area. A substantial majority of the
      households were facing mild to severe food insecurity and hunger for an extended
      period of time.

PMID- 22152761
TI  - Ethnic identity and gender as moderators of the association between
      discrimination and academic adjustment among Mexican-origin adolescents.
AB  - Existing work has identified perceived discrimination as a risk factor that may
      contribute to the relatively poorer academic outcomes exhibited by Mexican-origin
      adolescents in the U.S. The current study examined the longitudinal associations
      among perceived discrimination and three indices of adolescent adjustment in the
      school setting (i.e., grade point average, teacher reports of externalizing,
      adolescents' deviant peer associations) among 178 Mexican-origin adolescents (53%
      female). Ethnic identity affirmation was examined as a protective factor expected
      to reduce the negative effects of discrimination on adolescents' adjustment, and
      gender was examined as a potential moderator of the associations of interest.
      Findings indicated that the deleterious effects of discrimination on adolescents'
      adjustment in school were particularly salient for Mexican-origin male
      adolescents. Importantly, ethnic identity affirmation emerged as a protective
      factor for Mexican-origin male adolescents by buffering the negative effects of
      discrimination on their externalizing behaviors in school.

PMID- 22152762
TI  - Does my patient really have acute respiratory distress syndrome (ARDS)?

PMID- 22152763
TI  - Pandemic 2009 influenza A(H1N1) virus infection coinciding with invasive
      pulmonary aspergillosis in neutropenic patients.
AB  - SIn patients receiving anti-neoplastic chemotherapy, the impact of influenza on
      the incidence of invasive pulmonary aspergillosis (IPA) remains unknown. We
      matched data of the Cologne Cohort of Neutropenic Patients (CoCoNut) with records
      from the Institute for Virology and compared the findings to historical data.
      During the pandemic, we diagnosed influenza A(H1N1) in five patients with
      malignancies and febrile neutropenia refractory to antibiotic therapy. Probable
      IPA was diagnosed in three of these patients on the grounds of typical computed
      tomography morphology and microbiological results. Three of five patients
      receiving remission-induction chemotherapy for acute myeloid leukaemia developed
      aspergillosis although receiving posaconazole prophylaxis. In the 3 years before
      the influenza pandemic, only 2/77 patients of this group developed infection.
      Infection with influenza A(H1N1) may increase the risk for invasive aspergillosis
      in neutropenic patients. Pulmonary aspergillosis is an important additional
      differential diagnosis in neutropenic influenza patients with pneumonia.

PMID- 22152764
TI  - [Measurement of health-related quality of life in coronary heart disease: a
      review].
AB  - This paper introduces the development and application of health-related quality
      of life (HRQOL) scales in research on coronary heart disease (CHD). Currently,
      the scales for CHD patients have been more systematically developed and widely
      used in foreign countries, while domestically in China, they are developed
      successfully but problematically; research in this field has started later and
      the scales introduced are limited and not suitable for the entire range of
      domestic CHD patients. Thus, this paper introduces 26 HRQOL scales in research on
      CHD, including five generic scales, ten disease-specific scales from abroad and
      eleven scales originating from China. With the deficiency of HRQOL scales,
      especially that in traditional Chinese medicine and specific scales, this paper
      analyzes and summarizes the problems existing in development of scales. The
      authors also provide solutions in order to help the development and application
      of scales in further studies.

PMID- 22152765
TI  - [Correlation between traditional Chinese medicine syndromes and omics: a
      literature review].
AB  - As the post-genome era is approaching, omics has become a hot topic in the
      research field of life sciences and is also widely used in traditional Chinese
      medicine (TCM) research. For discussing the correlation between syndromes and
      omics, the authors explored the application of genomics, proteomics and
      metabonomics in the study of syndrome classification from the macroscopic view,
      after a systematic and normative study of the literature. The authors drew the
      conclusion that research into the correlation between syndromes and omics has
      great clinical significance in terms of the scientific application and
      quantification of TCM treatment based on syndrome differentiation.

PMID- 22152766
TI  - [Studies on dynamic changes in traditional Chinese medicine syndrome patterns for
      stroke using data-driven and model-driven approaches: a review].
AB  - Many clinical studies showed that the traditional Chinese medicine (TCM)
      syndromes in stroke have been dynamically changing since the onset of the
      disease. The changing of TCM syndromes can be attributed to multiple correlative
      factors such as age, sex, area distribution, underlying diseases, and
      constitutional factor. Data-driven methods involving multivariate statistical
      methods and descriptive approach have been used to analyze the regularity of
      dynamically changed TCM syndromes of stroke. However, expressing non-linear
      relationship between symptom or correlative factors and syndrome patterns by data
      driven models is challenging. Model-driven methods involving artificial neural
      networks and Bayesian networks are new methods for studying the changes in TCM
      syndromes in patients with stroke. In this review, the authors summarized the
      studies of dynamically changed patterns of stroke syndromes based on data-driven
      methods and some clinical trials on TCM syndromes based on model-driven methods.
      Further studies are needed to improve the understanding of the dynamically
      changing regularity of TCM syndromes for stroke by using model-driven methods so
      as to develop appropriate and timely TCM treatments.

PMID- 22152767
TI  - [Exploring the effects of Chinese medicine in improving uterine endometrial blood
      flow for increasing the successful rate of in vitro fertilization and embryo
      transfer].
AB  - Endometrial blood flow is directly related to endometrial receptivity thereby
      affecting in vitro fertilization and embryo transfer (IVF-ET) outcomes. In recent
      years a growing number of studies have shown that traditional Chinese medicine
      (TCM) can play a role to improve endometrial blood flow and embryo transfer.
      Studies have confirmed that formulas based on reinforcing kidney and activating
      blood can promote the formation of uterine endometrial blood vessels by adjusting
      expressions of a variety of vessel growth factors, and regulating nitric oxide
      level for inhibition of vascular smooth muscle contraction of the uterus.
      Treatments based on differentiation of syndromes are key to the theory of TCM.
      Differentiation of syndromes should be combined with biomedical disease
      diagnosis. It is also necessary to further clarify other endometrial blood flow
      disorders using TCM diagnostic methods. In these cases, drugs for reinforcing
      kidney and activating blood are relevant, but other medicines for smoothing liver
      qi and nourishing blood, as well as tonifying the spleen and generating blood may
      also be effective. Future clinical studies should focus on the observation of
      different types of TCM syndromes and the research on compatibility ratio and dose
      dependent relationship of Chinese medicines. Acupuncture has been used during IVF
      ET for more than 10 years. Electro-acupuncture can control the expansion of the
      uterine arteries by inhibiting the sympathetic nerves. However, acupuncture has
      not been proved to regulate endometrial arteries. To sum up, TCM can be applied
      to improve endometrial blood flow so as to increase birth rates in IVF-ET. The
      combination of Chinese and Western medicines and acupuncture application will
      increase their combined effect, thereby obtaining greater clinical benefits.

PMID- 22152768
TI  - Estimation of sample size and testing power (Part 3).
AB  - This article introduces the definition and sample size estimation of three
      special tests (namely, non-inferiority test, equivalence test and superiority
      test) for qualitative data with the design of one factor with two levels having a
      binary response variable. Non-inferiority test refers to the research design of
      which the objective is to verify that the efficacy of the experimental drug is
      not clinically inferior to that of the positive control drug. Equivalence test
      refers to the research design of which the objective is to verify that the
      experimental drug and the control drug have clinically equivalent efficacy.
      Superiority test refers to the research design of which the objective is to
      verify that the efficacy of the experimental drug is clinically superior to that
      of the control drug. By specific examples, this article introduces formulas of
      sample size estimation for the three special tests, and their SAS realization in
      detail.

PMID- 22152770
TI  - Ryodoraku as a tool monitoring the effects of walking exercise.
AB  - OBJECTIVE: To investigate the possibility of using Ryodoraku as a tool to
      indicate sympathetic neuronal activity. METHODS: Twenty-two female college
      students were assigned to an treadmill exercise program (three times a week for
      six weeks), and another 25 were assigned as controls. Skin conductance levels of
      the subjects were measured at 24 Ryodoraku points on the wrists and the ankles,
      along with heart rate variability (HRV) analysis, during and after the treadmill
      exercise period. RESULTS: The six-week exercise training resulted in a
      significant elevation of the average electrical conductance, which returned to
      the pre-training level after three months of cessation of the exercise training.
      CONCLUSION: HRV data have shown no similar changes, suggesting that Ryodoraku is
      a useful tool in detecting subtle, non-cardiovascular physical responses.

PMID- 22152769
TI  - Bufei Yishen Granule combined with acupoint-sticking therapy in patients with
      stable chronic obstructive pulmonary disease: study protocol of a multicenter,
      randomized, double-blind, active-controlled trial.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a serious disease
      constituting a major threat to public health. Current popularity of traditional
      Chinese medicine (TCM) in treating COPD implies its potential advantage in
      improving symptoms, reducing the frequency of acute exacerbation and improving
      the patients' quality of life. This study is to evaluate the efficacy and safety
      of a comprehensive intervention, Bufei Yishen Granule combined with acupoint
      sticking therapy, in patients with stable COPD. METHODS AND DESIGN: A
      multicenter, double-blind, double-dummy and randomized controlled design will be
      adopted. A total of 244 cases meeting the inclusion criteria will be enrolled
      into this study with 122 cases in the trial group and 122 in the control group,
      respectively. Patients in the trial group will receive Bufei Yishen Granule
      combined with acupoint-sticking therapy and dummy sustained-release theophylline,
      while patients in the control group will receive sustained-release theophylline
      and dummy Bufei Yishen Granule combined with dummy acupoint-sticking therapy. The
      frequency and duration of acute exacerbation, lung function, clinical symptoms,
      six-minute walking distance, dyspnea grade and quality of life will be observed
      during a four-month treatment period and a further six-month follow-up.
      DISCUSSION: It is hypothesized that Bufei Yishen Granule combined with acupoint
      sticking therapy will have beneficial effects in reducing the frequency and
      duration of acute exacerbation, ameliorating the symptoms, and improving the
      quality of life of patients with stable COPD. The results of this study will
      provide evidence for developing a TCM-based regimen for patients with COPD. TRIAL
      REGISTRATION: ChiCTR-TRC-11001409.

PMID- 22152771
TI  - [A study of diagnostic criteria for traditional Chinese medicine syndromes in
      osteoporosis].
AB  - OBJECTIVE: To establish diagnostic criteria for common traditional Chinese
      medicine (TCM) syndromes in osteoporosis. METHODS: Based on the collection and
      analysis of related medical literature, clinical investigation, and expert
      discussion, a draft of preliminary diagnostic criteria for the basic syndromes of
      TCM in patients with osteoporosis was formulated. Then it was used in clinic for
      verification and revised repeatedly until a formal version of diagnostic criteria
      was satisfactorily achieved. RESULTS: The basic syndromes listed in the
      diagnostic criteria for patients with osteoporosis consisted of two parts:
      qualitative diagnosis and localization diagnosis. Results of qualitative
      diagnosis showed that the qualitative syndromes included damage of essence,
      deficiency of vital energy, deficiency of yin, deficiency of yang and blood
      stasis. The localization diagnosis showed that location of osteoporosis is bone
      and corresponds to the kidney, and also involves liver, lung, spleen (stomach)
      and heart. The diagnostic content has established the specific symptoms and the
      non-specific symptoms during various stages. Each of the above syndromes could be
      diagnosed according to a specific combination of its corresponding symptoms or
      signs. The clinical verification results showed that the total matching ratio of
      qualitative diagnosis was 80.56% between the diagnoses made according to the
      criteria and the diagnoses acquired from the experts' experience, and the total
      matching ratio of localization diagnosis was 85.56%. CONCLUSION: The TCM syndrome
      diagnostic criteria for osteoporosis is generally consistent with TCM clinical
      practice, worthy of further popularization and application in clinical practice.

PMID- 22152772
TI  - [Influence of brightness value of supranasal point and apex nasi on dominant
      wavelength and excitation purity in complexion inspection of healthy adults].
AB  - OBJECTIVE: In this study, to analyze the influence of the brightness value of the
      supranasal point and the apex nasi on their dominant wavelength and excitation
      purity according to the spectrocolorimetry data of the supranasal point and the
      apex nasi in healthy adults that were collected based on optical spectrum
      colorimetry. METHODS: A total of 516 healthy adults were taken as the research
      subjects. The brightness, dominant wavelength and excitation purity values of the
      supranasal point and the apex nasi during the complexion inspection of subjects
      were calculated. This was based on the visible reflection spectrum, and the
      linear correlation/regression analysis between the brightness Y value and the
      dominant wavelength or excitation purity value. RESULTS: There was no correlation
      between the brightness Y value and the dominant wavelength of the normal
      supranasal point and the apex nasi; however, there was negative correlation
      between the brightness Y value and the excitation purity of the normal supranasal
      point and apex nasi. CONCLUSION: During the complexion inspection, the brightness
      Y value would not influence the dominant wavelength value, indicating that
      whiteness and/or blackness would not influence the normal individual complexion.
      However, the brightness Y value would influence the excitation purity of the
      supranasal point and the apex nasi, and the degree of saturation should be
      referred to as the brightness. This research provides a basic reference for
      diagnosing facial complexion in traditional Chinese medicine.

PMID- 22152773
TI  - [Effects of Astragalus polysaccharide on proliferation and Akt phosphorylation of
      the basal-like breast cancer cell line].
AB  - OBJECTIVE: To investigate the effects of Astragalus polysaccharide (APS) on
      proliferation of basal-like breast cancer cell line MDA-MB-468 cells and Akt
      phosphorylation in MDA-MB-468 cells. METHODS: APS at different concentrations was
      used to culture MDA-MB-468 cells for different time periods, and then
      proliferation of MDA-MB-468 cells was assayed using methyl thiazolyl tetrazolium
      (MTT) assay to determine the time- and dose-dependent effects of APS. For
      observing the effects of APS on phosphor-Akt (p-Akt), in-cell Western blot method
      was used after 1, 2, 4 and 7 d of culture in APS to detect protein expressions of
      p-Akt (Thr308) and p-Akt (Ser473). Protein levels of the key targets in
      p53/murine double minute 2 (MDM2) signaling pathway, such as p53, MDM2 and
      phosphatase and tensin homolog deleted on chromosome ten (PTEN) were also
      detected. After PTEN gene was silenced by small interfering RNA (siRNA) in MDA-MB
      468 cells, expressions of p-Akt (Thr308 and Ser473) were assayed by the in-cell
      Western blot method after 2 d of APS treatment. RESULTS: APS at 1 and 0.5 mg/mL
      concentrations effectively inhibited the proliferation of MDA-MB-468 cells and
      was used in subsequent tests. Compared with the control group, APS decreased the
      protein expression of p-Akt (Thr308) in MDA-MB-468 cells after 1-, 2-, 4- and 7
      day culture, and also decreased the protein expression of p-Akt (Ser473) and up
      regulated the protein expression of MDM2 in MDA-MB-468 cells after 1- and 2-day
      culture. Expressions of p53 and PTEN were up-regulated after 7 d of APS culture.
      After silencing PTEN gene by siRNA, APS could not mediate Akt phosphorylation.
      CONCLUSION: APS can inhibit proliferation of basal-like breast cancer cell line
      MDA-MB-468, and down-regulate the expression of Akt phosphorylation. The
      antiproliferation mechanisms may be related to its effects of up-regulating the
      expressions of p53 and PTEN by regulating p53/MDM2 positive and negative feedback
      loops.

PMID- 22152774
TI  - [Effects of Chinese herbal medicine Xinfeng Capsule on expressions of platelet
      activating factor and interleukins 6 and 17 in peripheral blood of rats with
      adjuvant arthritis].
AB  - OBJECTIVE: To observe the levels of platelet-activating factor (PAF), interleukin
      6 (IL-6) and IL-17 in peripheral blood of rats with adjuvant arthritis (AA), and
      the effects of Xinfeng Capsule (XFC), a compound traditional Chinese herbal
      medicine. METHODS: A total of 40 male Sprague-Dawley rats were randomized into
      normal control group, model group, methotrexate (MTX) group, Tripterygium
      Wilfordii polycoride Tablet (TPT) group, and XFC group, respectively. AA was
      induced in rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant
      in the right hindlimb. Contents of PAF, IL-6 and IL-17 in peripheral blood were
      measured by enzyme-linked immunosorbent assay. Body weight of rats, paw swelling
      and arthritis index (AI) were also observed. RESULTS: Compared with the normal
      control group, the levels of PAF, IL-6 and IL-17 in peripheral blood, paw
      swelling and AI were significantly increased in the model group (P<0.01).
      Compared with the model group, levels of PAF, IL-6 and IL-17, paw swelling and AI
      of the three drug-treated groups were significantly decreased (P<0.01). The body
      weight of the XFC group was significantly higher than those of the MTX- and TPT
      treated groups. Compared with the MTX- and TPT-treated groups, level of PAF in
      the XFC group was significantly increased (P<0.05). The level of PAF in
      peripheral blood of the AA rats was positively correlated with IL-6 and IL-17
      levels in peripheral blood, paw swelling and AI (P<0.01). CONCLUSION: The
      expression of PAF increases in peripheral blood of rats with AA, and it
      correlates with IL-6, IL-17, paw swelling and AI. XFC can decrease the expression
      of PAF, restrain infection induced by the activation of platelets, decrease the
      levels of IL-6 and IL-17, and hence decrease the paw swelling of rats with AA.

PMID- 22152775
TI  - [Medicated serum prepared with Chinese herbal medicine Zhizhen Recipe down
      regulates activity of nuclear factor-kappaB and expression of P-glycoprotein in
      human colorectal cancer multidrug-resistant cell line HCT-8/VCR].
AB  - OBJECTIVE: To investigate the effects of medicated serum prepared with Chinese
      herbal medicine Zhizhen Recipe (ZZR) on activity of nuclear factor-kappaB (NF
      kappaB) and expression and function of P-glycoprotein (P-gp) in human colorectal
      cancer multidrug-resistant cell line HCT-8/VCR. METHODS: The multidrug resistance
      of HCT-8/VCR cells was detected by cell counting kit-8 method, and the
      experimental concentrations of ZZR-medicated serum were determined by the same
      way. HCT-8 and HCT-8/VCR cells were treated with ZZR-medicated serum of medium
      dose for 24 h. The activity of NF-kappaB was determined by enzyme-linked
      immunosorbent assay. The intracellular distribution of P-gp was detected by laser
      scanning confocal microscopy, and the mean fluorescence intensity of rhodamine
      123 was detected by flow cytometry. RESULTS: ZZR-medicated sera with volume
      fraction of 8%, 16% and 32% of medium dose were confirmed as the experimental
      sera. Compared with the untreated group, NF-kappaB activities of the ZZR
      medicated serum groups (ZZR-medicated serum with volume fraction of 8%, 16% and
      32% of medium dose) were obviously down-regulated (P<0.01), which had a negative
      correlation with the concentrations. After interfering HCT-8/VCR with ZZR
      medicated serum of different concentrations for 24 h, P-gp in HCT-8/VCR
      transmitted gradually from cell membrane to cytoplasm and nuclei. Nuclei became
      pyknotic and cracking. Compared with the untreated group, the mean fluorescence
      intensities of ZZR-medicated serum groups declined with concentration gradients
      (P<0.01). The efflux of intracellular rhodamine 123 decreased, the wave crest
      shifted to right, and the intracellular fluorescence intensity strengthened
      (P<0.01). CONCLUSION: ZZR-medicated sera of experimental concentrations down
      regulate activity of NF-kappaB and expression and function of P-gp in human
      colorectal cancer multidrug-resistant cell line HCT-8/VCR and the effect is
      related to the concentrations.

PMID- 22152776
TI  - [Immunoregulatory mechanisms of an optimal Chinese herbal monomer compound in
      mice with allergic rhinitis].
AB  - OBJECTIVE: To study the immunoregulatory effect of an optimal Chinese herbal
      monomer compound, which consists of three monomers, namely, icariin, baicalin and
      Astragalus saponin I, in a mouse model of allergic rhinitis. METHODS: A mouse
      model of allergic rhinitis was established by intraperitoneal injection of
      ovalbumin and aluminum hydroxide gel suspension. The splenic lymphocytes of the
      mice were separated, cultured in 96-well plates and divided into three groups:
      control group, concanavalin A group and compound group. Splenic lymphocyte
      proliferation was detected by cell counting kit-8 method at different time
      points. Cell cycle distribution was observed by flow cytometry (FCM) also at
      different time points. The changes of intracellular calcium concentration of
      splenic lymphocytes were measured by fluorescence microplate reader after the
      cells were incubated with fluorescence probe Fluo-3/AM. RESULTS: The Chinese
      herbal monomer compound could inhibit cell proliferation induced by concanavalin
      A (P<0.01). And the inhibition presented a time-effect relationship. With
      extending of the action time, the inhibition rate gradually increased and reached
      peak at the 48th hour. FCM test revealed the fact that concanavalin A could
      promote cells to enter into the mitosis by reducing the percentage of cells in
      G0/G1 phases while increasing the percentage of cells in S and G(2)/M phases.
      Compared with the concanavalin A, the compound could increase the percentage of
      cells in G(0)/G(1) phases and at the same time reduce the percentage of cells in
      S and G(2)/M phases at different time points, with the effect most significant at
      the 24th hour (P<0.05 or P<0.01). The results of the test taken by the
      fluorescence microplate reader revealed that the fluorescence value of the
      concanavalin A group increased with time in the previous 24 h while the compound
      could reduce this trend obviously, thus reduce the intracellular calcium
      concentration (P<0.01). CONCLUSION: The Chinese herbal monomer compound can
      inhibit the proliferation of cultured splenic lymphocytes of mice with allergic
      rhinitis. The effects of the compound of lowering intracellular calcium
      concentration and arresting cell cycle at G(0)/G(1) phases from entering into S
      and G(2)/M phases are responsible for its antiproliferation activity.

PMID- 22152777
TI  - [Effects of Chinese herbal medicine Yiqi Huayu formula on substance P expression
      in skin ulcers of rats with diabetes mellitus].
AB  - OBJECTIVE: To investigate the effects of Chinese herbs for replenishing qi (Yiqi)
      and dissolving stasis (Huayu) on substance P expression in granulation tissue of
      skin ulcers in rats with diabetes mellitus. METHODS: One hundred male Sprague
      Dawley rats with back full-thickness skin lesion were randomly divided into five
      groups: ulcer control group, diabetic ulcer group, Yiqi Huayu herb group, Yiqi
      herb group, and Huayu herb group. Except ulcer control group, the other rats were
      also injected streptozotocin to induce diabetes mellitus. Rats in each group were
      given normal saline or herbal drugs for 15 d and the wound healing rate of the
      rats was observed on days 8 and 15, respectively. After treatment, the expression
      of substance P in granulation tissues of the rats was tested with
      immunohistochemical method and the immunohistochemical index was calculated.
      RESULTS: On the 8th and 15th days after treatment, the wound healing rate of the
      ulcer control group was higher than that of the diabetic ulcer group (P<0.01);
      the wound healing rates of all the treated groups were higher than that of the
      diabetic ulcer group (P<0.05); the wound healing rate of the Yiqi Huayu herb
      group was higher than those of the Yiqi herb group and the Huayu herb group
      (P<0.05). Compared with the diabetic ulcer group, the expression of substance P
      of the ulcer control group was increased (P<0.05); the expressions of substance P
      of the Yiqi Huayu herb group and the Huayu herb group were higher than that of
      the diabetic ulcer group (P<0.05). CONCLUSION: Yiqi Huayu herbs can promote wound
      healing in rats with diabetes mellitus by up-regulating the expression of
      substance P.

PMID- 22152778
TI  - Effects of combined leaf extract of Vernonia amygdalina and Azadirachta indica on
      hepatic morphology and hepatotoxicity markers in streptozotocin-induced diabetic
      rats.
AB  - OBJECTIVES: In this work, we studied liver morphology, markers of hepatic
      oxidative stress and some liver enzymes in diabetic rats treated with the
      combined leaf extract (CLE) of Vernonia amygdalina (bitter leaf) and Azadirachta
      indica (neem). METHODS: Diabetes was induced in fasted male Wistar rats with
      intraperitoneal injection of streptozotocin (STZ). Oral CLE (500 mg/kg body
      weight) and metformin (150 mg/kg body weight) were administered to different
      groups of diabetic rats for eight weeks. Blood glucose and change in body weight
      were estimated weekly. All animals were sacrificed under anaesthesia after eight
      weeks. Hepatic sections were stained with periodic acid-Schiff. Liver samples
      were homogenized and assayed for contents of malondialdehyde (MDA) and
      glutathione peroxidase (GPx), while the plasma was assayed for contents of
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST). RESULTS:
      Metformin and CLE treatment produced normoglycaemia in the diabetic rats in the
      course of the treatment period. Significant increases in body weight were
      observed in the treatment groups compared with the diabetic control rats
      (P<0.05). In the control and treatment groups, light microscopic study showed
      intact hepatic histology. Plasma ALT and AST were not significantly different
      from the control values in the CLE-treated rats. In addition, from week four
      onwards, blood glucose concentrations in the CLE-treated rats were not different
      from the normal control (P>0.05). Besides, hepatic MDA (P<0.05) significantly
      decreased in the CLE-treated rats compared with the normal control. CONCLUSION:
      These findings suggest that CLE ameliorates hyperglycemia and hepatic oxidative
      stress when administered to diabetic rats as a chronic regimen, and there was no
      morphologic or biochemical evidence of liver damage at the dose tested.

PMID- 22152779
TI  - Seeds of Syzygium cumini (L.) Skeels: potential for islet regeneration in
      experimental diabetes.
AB  - OBJECTIVE: The present study deals with the islet-regenerative potential of
      purified fraction of Syzygium cumini (L.) Skeels seeds (SC2) in streptozotocin
      (STZ)-induced diabetic mice. METHODS: Diabetes was induced in Swiss mice by
      single intraperitoneal injection of STZ (120 mg/kg). The treatment group mice
      were treated by administering oral dose of isolated SC2 fraction of S.cumini (2
      g/L) for 21 d. Blood glucose level and body weight measurements were conducted
      regularly during the 21 d. On the 20th day of the experiment, oral glucose
      tolerance test was performed on overnight fasted mice. Experimental mice were
      sacrificed at the end of the treatment and tissues were separated. The liver
      glucose-6-phosphate-dehydrogenase (G6PD) activity and contents of hepatic and
      muscle glycogens were measured; levels of plasma insulin and C-peptide were also
      measured. RESULTS: SC2-treated mice showed sustained reversal in experimental
      diabetes as evidenced by restoration of normoglycemia, increases in G6PD and
      hepatic and muscle glycogens along with increases in plasma insulin and C-peptide
      levels. The occurrence of neo-islets in histological studies suggested
      regenerative property of SC2. These neo-islets were found to be producing insulin
      in in vivo STZ-induced diabetic mice. CONCLUSION: These findings substantiate the
      action of SC2 fraction isolated from S.cumini seeds in islet regeneration and
      insulin secretion. Such regenerative approaches, in combination with other
      therapeutic strategies may provide a better means for the control and management
      of diabetes in the future.

PMID- 22152780
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      Defense, Qi, Nutrient and Blood Pattern Identification/Syndrome Differentiation
      (Part 1).

PMID- 22152781
TI  - A soyabean diet does not modify the activity of brown adipose tissue but alters
      the rate of lipolysis in the retroperitoneal white adipose tissue of male rats
      recovering from early-life malnutrition.
AB  - Nutritional recovery with a soyabean diet decreases body and fat weights when
      compared with a casein diet. We investigated whether the reduced adiposity
      observed in rats recovering from early-life malnutrition with a soyabean diet
      results from alterations in lipid metabolism in white adipose tissue (WAT) and/or
      brown adipose tissue (BAT). Male rats from mothers fed either 17 or 6 % protein
      during pregnancy and lactation were maintained on 17 % casein (CC and LC groups),
      17 % soyabean (CS and LS groups) or 6 % casein (LL group) diets over 60 d. The
      rats maintained on a soyabean diet had similar relative food intakes, but lower
      body and retroperitoneal WAT weights and a reduced lipid content in the
      retroperitoneal WAT. The insulin levels were lower in the recovered rats and were
      elevated in those fed a soyabean diet. Serum T3 concentration and uncoupling
      protein 1 content in the BAT were decreased in the recovered rats. The
      thermogenic capacity of the BAT was not affected by the soyabean diet. The
      lipogenesis rate in the retroperitoneal WAT was similar in all of the groups
      except for the LL group, which had exacerbated lipogenesis. The enhancement of
      the lipolysis rate by isoproterenol was decreased in white adipocytes from the
      soyabean-recovered rats and was elevated in adipocytes from the soyabean-control
      rats. Thus, in animals maintained on a soyabean diet, the proportions of fat
      deposits are determined by the lipolysis rate, which differs depending on the
      previous nutritional status.

PMID- 22152782
TI  - In search of psychosis biomarkers in high-risk populations: is the mismatch
      negativity the one we've been waiting for?

PMID- 22152783
TI  - Neural bases of emotional experience versus perception in schizophrenia.

PMID- 22152784
TI  - Single brain metastasis: resection followed by whole-brain irradiation and a
      boost to the metastatic site compared to whole-brain irradiation plus
      radiosurgery.
AB  - OBJECTIVE: The most appropriate treatment for a single brain metastasis is still
      controversial. This matched-pair analysis compared whole-brain irradiation plus
      radiosurgery (WBI+RS) to neurosurgical resection followed by whole-brain
      irradiation and a boost to the metastatic site (NR+WBI+B). METHODS: The data of
      46 patients treated with WBI+RS were matched 1:1 to 46 patients treated with
      NR+WBI+B with respect to age, gender, Karnofsky performance score (KPS), tumor
      type, extracerebral metastases, and interval from first diagnosis of cancer to
      treatment of the metastasis, RPA class, and GPA score. Both groups were compared
      for local control of the treated metastasis, intracerebral control, and survival.
      RESULTS: The 1-year local control rates were 85% after WBI+RS and 78% after
      NR+WBI+B (p=0.35). The 1-year intracerebral control rates were 74% and 68%
      (p=0.33), respectively. The 1-year survival rates were 64% and 58% (p=0.70),
      respectively. A multivariate analysis was not performed for local and
      intracerebral control, because no factor achieved significance on univariate
      analyses for these endpoints. Improved survival was associated with KPS>70
      (p=0.032), absence of extracerebral metastases (p=0.003), RPA-class 1 (p=0.014),
      and GPA score of 3.0-4.0 (p=0.010). CONCLUSION: Treatment outcomes were not
      significantly different after WBI+RS or NR+WBI+B. Because WBI+RS is less
      invasive, it may be preferable for many patients with a single brain metastasis.

PMID- 22152785
TI  - Transient Kluver-Bucy syndrome caused by cerebral edema following aneurysmal
      subarachnoid hemorrhage.

PMID- 22152786
TI  - Anti-N-methyl D-aspartate-type glutamate receptor antibody-positive limbic
      encephalitis in a patient with multiple sclerosis.

PMID- 22152787
TI  - Intraoperative indocyanine green angiography for microsurgical treatment of a
      craniocervical dural arteriovenous fistula.

PMID- 22152789
TI  - Liquid chromatography-mass spectrometry based global metabolite profiling: a
      review.
AB  - Untargeted, global metabolite profiling (often described as metabonomics or
      metabolomics) represents an expanding research topic and is, potentially, a major
      pillar for systems biology studies. To obtain holistic metabolic profiles from
      complex samples, such as biological fluids or tissue extracts, requires powerful,
      high resolution and information-rich analytical methods and for this
      spectroscopic technologies are generally used. Mass spectrometry, coupled to
      liquid chromatography (LC-MS), is increasingly being used for such investigations
      as a result of the significant advances in both technologies over the past
      decade. Here we try to critically review the topic of LC-MS-based global
      metabolic profiling and describe and compare the results offered by different
      analytical strategies and technologies. This review highlights the current
      challenges, limitations and opportunities of the current methodology.

PMID- 22152788
TI  - Raman spectroscopy for forensic examination of beta-ketophenethylamine "legal
      highs": reference and seized samples of cathinone derivatives.
AB  - Raman spectra of a representative range of beta-ketophenethylamine (beta-KP), the
      rapidly growing family of cathinone-related "legal high" recreational drugs, have
      been recorded. These spectra showed characteristic changes that were associated
      with the pattern of substitution on the aromatic rings, for example, the
      compounds carrying substituents at the 4- position could be distinguished from
      3,4-methylenedioxy "ecstasy" derivatives. They also showed small but detectable
      changes with differences in substitution on the ethylamine substituent. These
      features allowed the beta-KPs present in seized casework samples to be
      identified. The seized samples typically contained only small amounts of bulking
      agents, which meant that the band intensities of these components within averaged
      data were very small. In contrast, grid sampling normally gave at least some
      spectra which had a higher than average proportion of the bulking agent(s), which
      allowed them to also be identified. This study therefore demonstrates that Raman
      spectroscopy can be used both to provide a rapid, non-destructive technique for
      identification of this class of drugs in seized samples and to detect minor
      constituents, giving a composition profile which can be used for drugs
      intelligence work.

PMID- 22152790
TI  - Nanogold-functionalized magnetic beads with redox activity for sensitive
      electrochemical immunoassay of thyroid-stimulating hormone.
AB  - A new electrochemical immunosensor for sensitive determination of thyroid
      stimulating hormone (TSH) was designed by using redox-active nanogold
      functionalized magnetic beads (GoldMag) as signal tags on the nanogold-graphene
      interface. To construct such GoldMag nanostructures, polyethyleneimine
      functionalized magnetic beads (PEI-MBs) were initially prepared by using a wet
      chemical method, and the electroactive thionine molecules and gold nanoparticles
      were then alternately immobilized on the surface of PEI-MBs by using an opposite
      charged adsorption technique and an in situ synthesis method, respectively. The
      synthesized GoldMag nanostructures were utilized as signal tags for the label of
      horseradish peroxidase-anti-TSH conjugates (HRP-anti-TSH). With a sandwich-type
      immunoassay format, the conjugated signal tags on the transducer were increased
      with the increasing TSH concentration in the sample, thus enhancing the signal of
      the electrochemical immunosensor due to the labeled HRP toward the catalytic
      reduction of H(2)O(2). Under optimal conditions, the current was proportional to
      the logarithm of TSH concentration ranging from 0.01 to 20 MUIU mL(-1) in pH 6.0
      HAc-NaAc containing 6 mM H(2)O(2). The detection limit (LOD) was 0.005 MUIU mL(
      1) TSH at 3s(B). The immunosensor displayed an acceptable reproducibility,
      stability and selectivity. In addition, the methodology was evaluated with human
      serum specimens, receiving good correlation with results from commercially
      available electrochemiluminescent analyzer.

PMID- 22152791
TI  - Electrochemical bisphenol A sensor based on N-doped graphene sheets.
AB  - Bisphenol A (BPA), which could disrupt endocrine system and cause cancer, has
      been considered as an endocrine disruptor. Therefore, it is very important and
      necessary to develop a sensitive and selective method for detection of BPA.
      Herein, nitrogen-doped graphene sheets (N-GS) and chitosan (CS) were used to
      prepare electrochemical BPA sensor. Compared with graphene, N-GS has favorable
      electron transfer ability and electrocatalytic property, which could enhance the
      response signal towards BPA. CS also exhibits excellent film forming ability and
      improves the electrochemical behavior of N-GS modified electrode. The sensor
      exhibits a sensitive response to BPA in the range of 1.0*10(-8)-1.3*10(-6) mol L(
      1) with a low detection limit of 5.0*10(-9) mol L(-1) under the optimal
      conditions. Finally, this proposed sensor was successfully employed to determine
      BPA in water samples with satisfactory results.

PMID- 22152792
TI  - Number of graphene layers exhibiting an influence on oxidation of DNA bases:
      analytical parameters.
AB  - This article investigates the analytical performance of double-, few- and multi
      layer graphene upon oxidation of adenine and guanine. We observed that the
      sensitivity of differential pulse voltammetric response of guanine and adenine is
      significantly higher at few-layer graphene surface than single-layer graphene. We
      use glassy carbon electrode as substrate coated with graphenes. Our findings
      shall have profound influence on construction of graphene based genosensors.

PMID- 22152793
TI  - Electrochemical detection of hydrazine using a highly sensitive nanoporous gold
      electrode.
AB  - A facile alloy-dealloy technique performed in aqueous media was employed to
      prepare a nanoporous gold (NPG) electrode that demonstrated extremely high
      sensitivity toward hydrazine oxidation. An Ag(~60)Au(~40) alloy was
      electrodeposited at a constant potential on sequentially Cr- and Au-deposited
      indium tin oxide (Au/Cr/ITO) from a bath that contained sulfuric acid, thiourea,
      HAuCl(4).3H(2)O, and AgNO(3). The dealloying step was performed in concentrated
      HNO(3), where Ag in the alloy was selectively oxidized to leave the NPG
      structure. The NPG electrode was employed to study the hydrazine oxidation in
      basic phosphate buffer solution (PBS), and the results were compared with those
      obtained using the gold nanoparticle (AuNP)-modified ITO (AuNP/ITO) electrode.
      The NPG electrode demonstrated an unusual surface-confined behavior, which
      probably resulted from the thin-layer characteristics of the nano-pores.
      Hydrazine was detected by hydrodynamic chronoamperometry (HCA) at +0.2V (vs.
      Ag/AgCl). The steady-state oxidative current exhibited a linear dependence on the
      hydrazine concentration in the concentration range of 5.00 nM-2.05 mM, and the
      detection limit was 4.37 nM (sigma=3). This detection limit is the lower than the
      detection limits reported in the current literature concerning the
      electrochemical detection of hydrazine. The NPG electrode indeed demonstrates
      greater stability after hydrazine detection than the AuNP/ITO electrode.

PMID- 22152794
TI  - A simple and an efficient strategy to synthesize multi-component nanocomposites
      for biosensor applications.
AB  - We demonstrate that core-shell multi-component nanocomposites can be grown in
      situ at room temperature by a novel one-step approach without adding any
      reductant and stabilizer. We have presented a one-step method for the synthesis
      of multi-component nanocomposites in water solution, the multi-component
      nanocomposites could be produced directly and quickly in an in situ wet-chemical
      reaction. Here, Au-polypyrrole (PPy)/Prussian blue (PB) nanocomposites have been
      synthesized successfully under the same circumstance. With the addition of
      pyrrole monomers into mixture solutions, the autopolymerization of pyrrole into
      PPy and AuCl(4)(-) was reduced to elemental Au instantaneously as well as
      simultaneously. At the same time, PB produced along with elemental Au serving as
      a catalyst. Furthermore, we investigated the performance of Au-PPy/PB
      nanocomposites as amperometric sensor toward the reduction of H(2)O(2), which
      displayed high sensitivity, fast response and good stability. The peak current of
      H(2)O(2) increased linearly with the concentration of H(2)O(2) in the range from
      2.5*10(-9) to 1.2*10(-6)M, and the low detection limit of 8.3*10(-10)M (S/N=3)
      was obtained. Therefore, this work provides a new pathway to design and fabricate
      novel multi-component nanocomposites, which have unique characteristics and hold
      great applications in the fields of sensors, electrocatalysis and others.

PMID- 22152795
TI  - Determination of aminoglycoside residues by liquid chromatography and tandem mass
      spectrometry in a variety of matrices.
AB  - A quantitative LC-MS/MS method was developed for the determination of 13 commonly
      used aminoglycoside antibiotics in meat (pork muscle, fish, and veal livers and
      kidneys). The proposed method is sufficiently sensitive and highly selective.
      Unlike other previously reported methods, it uses a simple clean-up procedure
      based on a strong cation-exchange solid-phase cartridge that permits high sample
      extract loading volumes. A unique elution regime based on a volatile buffer at
      intermediately high pH value in combination with an organic solvent provides
      quantitative elution of the various aminoglycosides. This methodology ensured
      that neither a breakthrough of weakly retained aminoglycosides (e.g.
      spectinomycin) nor the incomplete elution of strongly retained analytes (e.g. neo
      and gentamycin) is observed. The single-step clean-up is fast and produces clean
      extracts that minimize matrix-related signal suppression in the electrospray
      interface.

PMID- 22152796
TI  - H, C, N and S stable isotopes and mineral profiles to objectively guarantee the
      authenticity of grated hard cheeses.
AB  - In compliance with the European law (EC No. 510/2006), geographical indications
      and designations of origin for agricultural products and foodstuffs must be
      protected against mislabelling. This is particularly important for PDO hard
      cheeses, as Parmigiano Reggiano, that can cost up to the double of the no-PDO
      competitors. This paper presents two statistical models, based on isotopic and
      elemental composition, able to trace the origin of cheese also in grated and
      shredded forms, for which it is not possible to check the logo fire-marked on the
      rind. One model is able to predict the origin of seven types of European hard
      cheeses (in a validation step, 236 samples out of 240 are correctly recognised)
      and the other specifically to discriminate the PDO Parmigiano Reggiano cheese
      from 9 European and 2 extra-European imitators (260 out of 264 correct
      classifications). Both models are based on Random Forests. The most significant
      variables for cheese traceability common in both models are delta(13)C,
      delta(2)H, delta(15)N, delta(34)S and Sr, Cu, Mo, Re, Na, U, Bi, Ni, Fe, Mn, Ga,
      Se, and Li. These variables are linked not only to geography, but also to cow
      diet and cheese making processes.

PMID- 22152797
TI  - Analysis of multiplex endogenous estrogen metabolites in human urine using ultra
      fast liquid chromatography-tandem mass spectrometry: a case study for breast
      cancer.
AB  - A rapid, sensitive, specific and accurate analytical method of ultra-fast liquid
      chromatography combined with tandem mass spectrometry (UFLC-MS/MS) was
      established for simultaneous quantitative analysis of 16 distinct endogenous
      estrogens and their metabolites (EMs) in postmenopausal female urine. The
      quantitative method utilized a hydrolysis/extraction/derivatization step and a
      UFLC system to achieve separation in 16 min. The lower limit of quantitation for
      each estrogen metabolite was 2 pg mL(-1) with the percent recovery of a known
      added amount of estrogen at 93.2-109.3%. The intra-batch accuracy and precision
      for all analytes were 87.5-107.7% and 0.6-11.7%, respectively, while inter-batch
      accuracy and precision were 87.0-105.8% and 1.2-10.2%, respectively. Using this
      developed and validated method, the comprehensive metabolic profiling of 16 EMs
      in urine samples of 86 postmenopausal female breast cancer patients and 36
      healthy controls was investigated by systematic statistical analysis. As a
      result, the circulating levels of 6 EMs were found to be different by a
      comparison of patients and healthy controls. The parent estrogens, estrone (E1)
      and 17beta-estradiol (E2), as well as 2-hydroxyestradiol (2-OHE2) and 4
      hydroxyestradiol (4-OHE2) were produced in higher abundance, whereas 16alpha
      hydroxyestrone (16alpha-OHE1) and 2-methoxyestradiol (2-MeOE2) were decreased in
      the breast cancer group. 2-OHE2 and 4-OHE2 in particular showed significant
      elevation in patients, which are consistent with the carcinogenic mechanism
      hypothesis that catechol estrogens can react with DNA via quinones, resulting in
      mutations to induce breast cancer. Thus, 2,4-hydroxylation may be the dominant
      metabolic pathway for parent estrogens rather than 16alpha-hydroxylation. The
      lower level of 2-MeOE2 in the breast cancer group was believed to correlate with
      its protective effect against tumor formation. This study could provide valuable
      information on the association of the EM metabolic pathway with carcinogenesis as
      well as identify potential biomarkers for estrogen-induced breast cancer risk.

PMID- 22152798
TI  - Microchip capillary electrophoresis-electrospray ionization-mass spectrometry of
      intact proteins using uncoated Ormocomp microchips.
AB  - We present rapid (<5 min) and efficient intact protein analysis by mass
      spectrometry (MS) using fully microfabricated and monolithically integrated
      capillary electrophoresis-electrospray ionization (CE-ESI) microchips. The
      microchips are fabricated fully of commercial inorganic-organic hybrid material,
      Ormocomp, by UV-embossing and adhesive Ormocomp-Ormocomp bonding (CE
      microchannels). A sheath-flow ESI interface is monolithically integrated with the
      UV-embossed separation channels by cutting a rectangular emitter tip in the end
      with a dicing saw. As a result, electrospray was produced from the corner of chip
      with good reproducibility between parallel tips (stability within 3.8-9.2% RSD).
      Thanks to its inherent biocompatibility and stable (negative) surface charge,
      Ormocomp microchips enable efficient intact protein analysis with up to ~10(4)
      theoretical separation plates per meter without any chemical or physical surface
      modification before analysis. The same microchip setup is also feasible for rapid
      peptide sequencing and mass fingerprinting and shows excellent migration time
      repeatability from run to run for both peptides (5.6-5.9% RSD, n=4) and intact
      proteins (1.3-7.5% RSD, n=3). Thus, the Ormocomp microchips provide a versatile
      new tool for MS-based proteomics. Particularly, the feasibility of the Ormocomp
      chips for rapid analysis of intact proteins with such a simple setup is a
      valuable increment to the current technology.

PMID- 22152799
TI  - Improved detection of phosphopeptides by negative ion matrix-assisted laser
      desorption/ionization mass spectrometry using a proton sponge co-matrix.
AB  - Analysis of phosphopeptides is an important task in proteomic studies. Matrix
      assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a technique
      very commonly used for such a purpose. Analysis of phosphopeptides by MALDI-MS
      is, however, still a challenging task due to the low ionization efficiency of
      phosphopeptides. In this study, we reported that by using a proton sponge 1,8
      bis(dimethyl-amino)naphthalene (DMAN) as a co-matrix, detection of
      phosphopeptides by negative ion MALDI-MS could be greatly improved. Combination
      of DMAN with another matrix 6-aza-2-thiothymine (ATT) and additive diammonium
      hydrogen citrate (DHC) allowed much lower limit of detection, significantly
      reduced signal suppression effects and improved position-to-position
      reproducibility for detection of phosphopeptides by negative ion MALDI-MS.
      Potential applications of the matrix system in qualification of phosphopeptides
      and analysis of proteolytic digests of phosphorylated proteins were also
      demonstrated in this study.

PMID- 22152800
TI  - Preparation of a novel molecularly imprinted polymer by the sol-gel process for
      sensing creatinine.
AB  - A novel molecularly imprinted polymer (MIP) was prepared and used as an
      artificial receptor for creatinine (Cre). A sol-gel process was used to prepare
      the MIP. Tetraethoxysilane (TEOS) was employed as the crosslinker for the
      formation of a silica matrix for the MIP. Aluminum ion (Al(3+)) was chosen as the
      dopant to generate Lewis acid sites in the silica matrix for interactions with
      Cre. Through the sol-gel process, a polymeric matrix with memory sites for Cre
      was obtained, and this is mentioned here as the molecularly imprinted polymer for
      creatinine (MIP(Cre)). The imprinting efficiency of MIP(Cre) was evaluated by
      contrasting the adsorbed amount of Cre by MIP(Cre) with that by the corresponding
      non-imprinted polymer (NIP). Creatine (Cn), N-hydroxysuccinimide (NHS), and L
      tyrosine (L-tyr) were selected as interferences to study the selectivity of the
      MIP(Cre). The interference studies were also conducted using binary mixtures,
      such as Cre/Cn, Cre/NHS, and Cre/L-tyr. All these studies reveal that the
      MIP(Cre) possess a remarkable affinity for Cre. The crucial role of Al(3+) in
      this system is discussed in detail. Furthermore, the effects of concentrations of
      Al(3+) and TEOS on the adsorbed amount of Cre by MIP(Cre) were also investigated.

PMID- 22152801
TI  - A novel optical thrombin aptasensor based on magnetic nanoparticles and split
      DNAzyme.
AB  - In this paper, we report a novel and sensitive optical sensing protocol for
      thrombin detection based on magnetic nanoparticles (MNPs) and thrombin aptamer,
      employing split HRP-mimicking DNAzyme halves as its sensing element, which can
      catalyze the H(2)O(2)-mediated oxidation of the colorless ABTS into a blue-green
      product. A single nucleotide containing the recognition element and sensing
      element is utilized in our protocol. The specific recognition of thrombin and its
      aptamer leads to the structure deformation of the DNA strands and causes the
      split of the DNAzyme halves. Therefore, the decrease of absorption spectra can be
      recorded by the UV-visible Spectrophotometer. DNA-coated MNPs are utilized to
      separate the interferential materials from the analyst, thus making this assay
      can be applied in the detection of thrombin in complex samples, such as human
      plasma. This original, sensitive and cost-effective assay showed favorable
      recognition for thrombin. The absorbance signals with the concentration of
      thrombin over a range from 0.5 to 20 nM and the detection limit of thrombin was
      0.5 nM. The controlled experiments showed that thrombin signal was not interfered
      in the presence of other co-existence proteins.

PMID- 22152802
TI  - High-performance liquid chromatographic method to evaluate the hydrogen atom
      transfer during reaction between 1,1-diphenyl-2-picryl-hydrazyl radical and
      antioxidants.
AB  - 1,1-Diphenyl-2-picrylhydrazyl (DPPH.) is a stable nitrogen centred radical widely
      used to evaluate direct radical scavenging properties of various synthetic or
      natural antioxidants (AOs). The bleaching rate of DPPH. absorbance at 515nm is
      usually monitored for this purpose. In order to avoid the interference of complex
      coloured natural products used as antioxidant supplements or cosmetics, HPLC
      systems have been reported as alternative techniques to spectrophotometry. They
      also rely upon measurement of DPPH. quenching rate and none of them permits to
      identify and measure 1,1-diphenyl-2-picryl-hydrazine (DPPH-H), the reduced
      product of DPPH. resulting from hydrogen atom transfer (HAT), which is the main
      mechanism of the reaction between DPPH. and AOs. We presently report an HPLC
      method devoted to the simultaneous measurement of DPPH. and DPPH-H. Both were
      fully separated on a C18 column eluted with acetonitrile-10 mM ammonium citrate
      buffer pH 6.8 (70:30, v/v) and detected at 330 nm. Adsorption process of DPPH.
      onto materials of the HPLC system was pointed out. Consequently, the linearity
      range observed for DPPH. was restricted, thus a much lower limit of detection was
      obtained for DPPH-H than for DPPH. using standards (0.02 and 14 MUM,
      respectively). The method was applied to three commonly used AOs, i.e.
      Trolox((r)), ascorbic acid and GSH, and compared with spectrophotometry. Further
      application to complex matrices (cell culture media, vegetal extracts) and
      nanomaterials demonstrated (i) its usefulness because of higher selectivity than
      colorimetry, and (ii) its help to investigate the mechanisms occurring with the
      free radical.

PMID- 22152804
TI  - [The activation of TRIF-dependent signaling pathway in THP-1 cells induced by
      beta2 GPI/anti-beta2 GPI antibodies complex].
AB  - AIM: To observe whether the TIR-domain-containing adaptor inducing interferon
      beta (TRIF) is activated in THP-1 cells treated with beta2 GPI/anti-beta2 GPI
      complex and investigate the roles of TRIF-dependent signaling pathway of Toll
      like receptor 4 (TLR4) in antiphospholipid syndrome (APS). METHODS: The total RNA
      was extracted and the protein lysates were collected from THP-1 cells stimulated
      with beta2 GPI/anti-beta2 GPI complex. And the level of TRIF mRNA in THP-1 cells
      was detected by Real-time PCR (RT-PCR), TRIF protein expression was investigated
      by western blotting, respectively. Furthermore, whether TLR4 inhibitor, TAK-242,
      could interrupt the expression of TRIF as well as some inflammatory cytokines
      such as IL-6, IL-8 and TNF-alpha in THP-1 cells stimulated with beta2 GPI/anti
      beta2 GPI complex was also investigated. RESULTS: Both mRNA and protein levels of
      TRIF could be significantly increased in THP-1 cells with treatment of beta2
      GPI/anti-beta2 GPI complex (100 mg/L). The expression of TRIF was shown in a
      manner of time-dependence, with the maximal levels at 1 hour (mRNA) and 2 hour
      (protein) stimulation respectively. The beta2 GPI/anti-beta2 GPI complex-induced
      TRIF and inflammatory cytokines including IL-6, IL-8 and TNF-alpha expression in
      THP-1 cells could be inhibited by TAK-242 (5 MUmol/L). CONCLUSION: TRIF-dependent
      signaling pathway of Toll-like receptor 4 is involved in the activation of THP-1
      cells induced by beta2 GPI/anti-beta2GPI complex, suggesting that TRIF may play
      an important role in the pathogenesis of antiphospholipid syndrome.

PMID- 22152803
TI  - Guidelines for the treatment of acute ischaemic stroke.
AB  - INTRODUCTION: Update of Acute Ischaemic Stroke Treatment Guidelines of the
      Spanish Neurological Society based on a critical review of the literature.
      Recommendations are made based on levels of evidence from published data and
      studies. DEVELOPMENT: Organized systems of care should be implemented to ensure
      access to the optimal management of all acute stroke patients in stroke units.
      Standard of care should include treatment of blood pressure (should only be
      treated if values are over 185/105 mmHg), treatment of hyperglycaemia over 155
      mg/dl, and treatment of body temperature with antipyretic drugs if it rises above
      37.5  degrees C. Neurological and systemic complications must be prevented and
      promptly treated. Decompressive hemicraniectomy should be considered in cases of
      malignant cerebral oedema. Intravenous thrombolysis with rtPA should be
      administered within 4.5 hours from symptom onset, except when there are
      contraindications. Intra-arterial pharmacological thrombolysis can be considered
      within 6 hours, and mechanical thrombectomy within 8 hours from onset, for
      anterior circulation strokes, while a wider window of opportunity up to 12-24
      hours is feasible for posterior strokes. There is not enough evidence to
      recommend routine use of the so called neuroprotective drugs. Anticoagulation
      should be administered to patients with cerebral vein thrombosis. Rehabilitation
      should be started as early as possible. CONCLUSION: Treatment of acute ischaemic
      stroke includes management of patients in stroke units. Systemic thrombolysis
      should be considered within 4.5 hours from symptom onset. Intra-arterial
      approaches with a wider window of opportunity can be an option in certain cases.
      Protective and restorative therapies are being investigated.

PMID- 22152805
TI  - [Cloning and expression of human interleukin-32 and studies on its bioactivity].
AB  - AIM: To clone human interleukin-32(hIL-32) gene and express it in E.coli
      efficiently. METHODS: The gene of hIL-32 was amplified by RT-PCR from human
      peripheral blood mononuclear cells (PBMC) which stimulated with Con A for 60 h.
      The PCR product was inserted into the pMD18-T vector. The hIL-32 cDNA confirmed
      by sequencing was inserted into expression vector pET-30a(+) and expressed in
      E.coli BL21(DE3) strain. The hIL-32 protein expression was induced by IPTG and
      assayed by SDS-PAGE and coomassie blue stain. The recombination protein was
      identified by Western blot and its biological activity was analyzed. RESULTS: DNA
      sequencing confirmed that the cloned cDNA was identical to the published sequence
      of hIL-32 that the nucleotide sequence of this gene was 567 bp. The recombinant
      plasmid pET30a-hIL32 was transformed into E.coli BL21(DE3) strain for expression.
      An expected 28 kDa protein of hIL-32  was found mainly in the induced host
      strains by SDS-PAGE and coomassie blue stain. The 28 kDa protein was recognized
      by anti-IL-32 antibody in western blot. The purified recombination protein could
      induce the producing of IL-6 in the human PBMC. CONCLUSION: We have successfully
      cloned the gene and expressed the protein of hIL-32 and the expressed protein has
      specific bioactivity.

PMID- 22152806
TI  - [Construction of human CXCR3B gene transfected cell line,   identification and
      study of its biological function].
AB  - AIM: To construct recombinant human CXCR3B gene expression vector and obtain L929
      CXCR3B gene transfected cell line for stably expressing human CXCR3B. METHODS:
      Human CXCR3B gene of full length was amplified by PCR from the plasmid pMD19
      T/huCXCR3A. Then,   it was inserted into eukaryotic expression vector pIRES2-EGFP
      to construct recombinant vector pIRES2-EGFP/huCXCR3B. The recombinant vector was
      transfected into L929 cells with Lipofectamine(TM); 2000,  and cell clones stably
      expressing human CXCR3B molecule were screened by G418.We used FCM and RT-PCR to
      verify expression of CXCR3B from protein level and gene level. The ability of
      proliferation of L929-huCXCR3B under the circumstance of CXCR3B ligand called Mig
      was analyzed via MTT methods. RESULTS: We have constructed recombinant human
      CXCR3B gene expression vector and obtained L929-huCXCR3B gene transfected cell
      line which can stably express human CXCR3B molecule. The positive expression rate
      of CXCR3B on L929-huCXCR3B cells was 93&.  The  result of MTT assay showed  that
      the proliferation of L929-huCXCR3B cells were inhibited when the cells were
      cocultured with Mig after 24 h,  48 h and 72 h,  and the inhibition ratio were
      41.44&,  44.01& and 24.80& respectively. CONCLUSION: Construction of L929
      huCXCR3B cell line has laid a good foundation on research of the CXCR3B signal
      pathway and preparation of the CXCR3B monoclonal antibody.

PMID- 22152807
TI  - [The pathogenesis of CD4(+)T cells infiltrated into the spinal cord in rat SNL
      model].
AB  - AIM: To explore the infiltration pathogenesis of CD4(+);T cells following the
      spinal nerve ligation. METHODS: Healthy adult male SD rats were randomly divided
      into the spinal nerve ligation group (Tx),  sham operation group (S),  control
      group (C). the 50& mechanical paw withdrawal threshold ( 50&MWT ) was determined
      by up-down method;  CD4(+);T cells infiltration was assessed by FACS;  the mRNA
      levels of CCL2,  CCL5 and CXCL10 were quantitated by RT-qPCR;  serum cytokines
      were tested by ELISA kits. RESULTS: After 3 days since operation,  50&MWT of Tx
      group was significantly reduced (P<0.01) comparing with S group,  C group;  on
      day 14,  50&MWT was up to the minimum value;  whereas S group and C group were no
      difference (P>0.05). After 7 days since operation,  CD4(+);T cells infiltration
      into lumbar segments of the spinal cord in the Tx group increased significantly
      (P<0.01),  and the CCL2,  CCL5mRNA expression increased (P<0.05);  on day 14, 
      the CD4(+);T cells infiltration in Tx group was higher than S group,  C group; 
      but there was no statistical significance. On day 7 and 14 days,  serum levels of
      cytokines were no difference in the three groups. CONCLUSION: Following spinal
      nerve ligation,  high expression of chemokine promoted peripheral CD4(+);T cells
      to infiltrate into spinal cord;  and the infiltrated CD4(+);T cells maintained
      the neuropathic pain.

PMID- 22152808
TI  - [Detection for KIR gene with use of SYBR green I real-time PCR].
AB  - AIM: To develope a novel real-time PCR method for KIR genotyping. METHODS: KIR
      genotyping is performed using 16 real-time PCR reactions,  each containing two
      three KIR-specific primers,  a pair of internal positive control primers and a
      fluorescence dye,  SYBR Green I. By the analysis of the Tm and the characteristic
      of the melting curve of the amplified products,  we identified the presence or
      absence of 16 KIR genes. A variety of dilution folds were made to detect the
      sensitivity of this method. RESULTS: KIR genes were effectively genotyped by the
      analysis of the melting curve. This method can be used to detect KIR genes even
      from 0.1 ng of DNA.  The feasibility of this method was tested by genotyping 10
      DNA samples from Peripheral blood and 10 DNA samples from cervical cell.
      CONCLUSION: We developed a novel real-time PCR assay with SYBR Green I,  which is
      a simple,  rapid,  sensitive,  real-time and environmental method. It provides
      the possibility of the automated KIR genotyping.

PMID- 22152809
TI  - [Effects of fractalkine on the expression of inflammatory substances in LPS
      activated microglia cells].
AB  - AIM: To investigate the effect of fractalkine on the expression of the tumor
      necrosis factor-alpha(TNF-alpha), interleukin-1beta (IL-1beta), and nitric oxide
      (NO) in LPS-activated murine microglia cells line N9. METHODS: In vitro LPS
      activated microglia cells were treated for 24 h in the presence of fractalkine.
      The level of TNF-alpha and IL-1beta in the culture supernatants were measured by
      enzyme-linked immunosorbent assay (ELISA), The level of NO in the culture
      supernatants were quantitated by the NO test assay. RESULTS: The concentration of
      TNF-alpha, IL-1beta and NO in the culture supernatants evidently increased in LPS
      activated microglia cells groups and prominently decreased by the fractalkine co
      incubated. CONCLUSION: It is thus concluded that fractalkine has neuroprotective
      functions by inhibiting the expression of inflammatory factor in activated
      microglia cells.

PMID- 22152810
TI  - [Effects of Mycobacterium tuberculosis Hsp16.3 protein on the autophagy function
      of mice macrophages].
AB  - AIM: To investisate  the inhibition of Hsp-16.3 on the autophagosomes formation
      of macrophages. METHODS: Mouse  RAW264.7 macrophages   were   induced by
      rapamycin (50 ng/MUL) following infection with M.tuberculosis H37Rv strains, 
      thereafter,  co-incubated with Hsp16.3 protein (25 MUg/mL). The effects of
      Hsp16.3 protein on the autophagosomes formation was observed with   transmission
      electron microscope. The expression of autophagy-related genes (atg8) for
      macrophages was detected by Western blotting. RESULTS: It   was found that
      rapamycin-induced autophagy of macrophages infected with M.tuberculosis H37Rv
      enhanced localization of mycobacteria with autophagosomes. Hsp16.3 protein
      inhibits autophagosome formation and affects M.tuberculosis survival inside
      infected macrophages. Furthermore,  Hsp16.3 protein significantly increased
      M.tuberculosis colony forming units (CFU),  and decreased the expression of
      microtubule-associated protein light chain-3 (LC3) expression level  (P<0.05).
      CONCLUSION: The  results showed  that Hsp16.3 protein inhibits the formation of
      autophagosomes by regulating the expression  of LC3 protein.

PMID- 22152811
TI  - [Ethyl pyruvate inhibited HMGB1 expression induced by LPS in macrophages].
AB  - AIM: To elucidate the mechanism of ethyl pyruvate (EP) inhabit high mobility
      group protein B1 (HMGB1)expression and releasing in macrophage induced by
      lipopolysaccharide(LPS). METHODS: The murine macrophage-like cell line RAW264.7
      cultured in vitro divided into LPS group and LPS+EP group. The expression of
      HMGB1 mRNA in cultured cell was determined by RT-PCR. The cytoplasmic and nuclear
      HMGB1 levels were detected by Western blot. The contents of HMGB1  and TNF-alpha
      and IL-6 protein in cultured cells supernatant were detected by ELISA.
      Immunocytochemistry and confocal laser-scanning microscopy were used to confirm
      the relocation and distribution of intracellular HMGB1 protein in RAW264.7 cells.
      RESULTS: HMGB1 mRNA expression in the LPS+EP group was significantly lower than
      in LPS alone, at 24, 36 and 48 hours. In the LPS+EP stimulation group,  the
      cytoplasm stained weakly while the nuclear stain was stronger than that of the
      LPS group at the same time points. Both TNF-alpha  and  IL-6 levels in LPS+EP
      group were significantly lower than those in the LPS group at the same time
      points. EP also effectively prevented the release of HMGB1 protein. CONCLUSION:
      EP inhibits HMGB1 expression and release from LPS-stimulated macrophages.

PMID- 22152812
TI  - [Expression of RhoA in the lung tissue of acute lung injury rats and the
      influence of RhoA on the expression of IL-8 and IL-10].
AB  - AIM: To investigate the expression of RhoA in the lung tissue of acute lung
      injury (ALI) rats induced by oleic acid (OA) and explore the influence of RhoA on
      the level of IL-8 and  IL-10 in serum. Discussion RhoA and acute lung injury
      relationship. METHODS: Establish rat oleic acid acute lung injury model,  Wet/Dry
      weights (W/D) were detected. Pathological changes of the lung tissue were
      examined. The levels of IL-8 and IL-10 in serum were detected by ELISA and the
      expression of RhoA in homogenate of lung tissue was determined by PCR. RESULTS:
      W/D and ALI score in ALI group at 6,  12, 24 and 48 h were higher than those in
      control group (P<0.01) and intervention group at the same time point (P<0.05).
      The level of IL-10(ng/L) in serum in ALI group at  2,  6,  12, 24 and 48 h was
      remarkably higher than that in control group (P<0.01),  but was lower compared
      with intervention group at the same time point (P<0.01). The level of IL-8(pg/L)
      in serum at  2, 6, 12, 24 and 48 h in ALI group were higher than those in control
      group(P<0.01)  and intervention group at the same time point(P<0.01).Compared
      with that of control group,  the expression of RhoA in homogenate of lung tissue
      in ALI group at 2,  6, 12, 24 and 48 h was higher(P<0.01),  but there was no
      difference between ALI group and intervention group at the same time
      point(P>0.05). CONCLUSION: The expression of RhoA in lung tissue of ALI rats
      induced by OA is increased. RhoA expression increase that can cause lung damage
      degree increase in rats. RhoA can aggravate the pathology changes of ALI rats, 
      which might be related to up regulating expression of IL-8 and down regulating
      expression of IL-10 by RhoA.

PMID- 22152813
TI  - [Studies on the fibroblast proliferation and transdifferentiation for
      myofibroblast from skin lesion of the patients with systemic sclerosis repressed
      by H2 Relaxin].
AB  - AIM: The study was to explore the effects of the fibroblast transdifferentiation
      for myofibroblast (MFB) in the pathogenesis of systemic sclerosis (SSc) and to
      research the effect mechanism of H2 Relaxin (H2-RLX) against fibrosis in SSc.
      METHODS: The fibroblasts derived from the skin lesion of the SSc patients and
      normal skin tissue were respectively cultured in vitro and demonstrated. The MFB
      proportion in fibroblast was known by alpha-smooth muscle actin (alpha-SMA) in
      fibroblast culture detected with immunohistochemistry for qualitative study and
      ELISA for quantitative analysis. The influence on fibroblast proliferation and
      transdifferentiation for MFB was observed by adding H2-RLX. RESULTS: There were
      no apparent differences for cell morphology between the fibroblasts from SSc
      patients and controls. The means of positive alpha-SMA in SSc group were higher
      than those in controls (P<0.01). With culture time extended,  alpha-SMA levels of
      the two groups all increased gradually (P<0.01 all),  but there were higher alpha
      SMA levels in SSc group than those in controls separately at H24,  H48,  H72 in
      culture (P<0.05 all). Fibroblast proliferation and alpha-SMA levels were not
      influenced after adding 1 MUg/L of H2-RLX,  but 10 MUg/L and 100 MUg/L of it
      could completely inhibit the fibroblast proliferation and alpha-SMA levels
      (P<0.05 all),  with the strongest repressing effect after adding 100 MUg/L of it.
      CONCLUSION: There is a specific property of fibroblasts transdifferentiation for
      MFB strongly from the skin lesion of the SSc patients. H2-RLX could give play to
      the antifibrotic effects by repressing the fibroblast proliferation and
      transdifferentiation for MFB in SSc.

PMID- 22152814
TI  - [Comparision of intracellular localization and recycling route of mouse nepmucin
      and CD31 in endothelial cells].
AB  - AIM: To compare the localization and recycling between nepmucin and CD31
      molecules on transfected endothelial cells,  and attempted to clarify the
      recycling mechanisms of nepmucin in endothelial cells. METHODS: Recycling assay
      and internalization assay were employed to compare the localization and recycling
      pathway of nepmucin and CD31. The internalized and recycling nepmucin and CD31
      molecules on transfected endothelial cells were double or single stained with
      specific fluorchrome-labeled monoclonal antibodies against nepmucin (Alexa Fluor
      488-ZAQ5) and/or CD31 (Alexa Fluor 488-anti-CD31 or Alexa Fluor 594-anti-CD31), 
      then observed under confocal microscopy. RESULTS: Mouse nepmucin underwent
      intracellular recycling like CD31,  but which recycling rate was significantly
      lower. The CD31 and nepmucin molecules showed largely distinct localization in
      endothelial cells. CD31 was found mainly on the cell surface,  while nepmucin was
      found predominantly in the deep area of cytoplasm and partly on the cell
      membrane. CONCLUSION: The distribution of mouse nepmucin in endothelial cells are
      different from CD31. Nepmucin underwent intracellular recycling like CD31 but
      employed different mechanisms.

PMID- 22152815
TI  - [Construction and expression of dual promoter lentiviral vector containing TFR
      and VEGF genes].
AB  - AIM: To construct a dual promoter lentivira vector containing TFR and VEGF gene,
      and detect the expression of TFR and VEGF genes in MSCs of Chinese mini-swine.
      METHODS: The TFR and VEGF gene were amplified by polymerase chain reaction and
      cloned into pLenti-GFP-Neo after the CMV and SV40 promoter respectively, to
      generate the lentivira vector pLenti-TG-VEGF. The four-plasmids lentiviral vector
      system(pRsv-REV, pMDlg-pRRE, pMD2G and pLenti-TG-VEGF)were cotransfected into
      human embryonic kidney 293 T cells with Lipofectin 2000 reagent. The packaged
      virus was harvested 72 h later. MSCs were infected by lentivirus carrying TFR and
      VEGF genes. Western blotting was used to detect the expression of TFR and VEGF
      genes in the viral infected MSCs. RESULTS: Restriction endonuclease digestion
      analysis and DNA sequencing demonstrated that the dual promoter lentivirus vector
      containing TFR and VEGF genes were constructed successfully. MSCs could be
      successfully infected by the recombinant lentivirus. Expression of TFR and VEGF
      protein could be detected in the infected MSCs by Western blotting. CONCLUSION:
      The dual promoter lentiviral vector containing TFR and VEGF genes are constructed
      successfully which provides basis for future research on Cardiac molecular
      imaging of cell transplantation.

PMID- 22152816
TI  - [Change in the pattern of peripheral blood TCR V beta gene repertoire in
      occupational lead-exposed workers].
AB  - AIM: To investigate the distribution and clonality of TCR Vbeta subfamily in
      peripheral blood from workers exposed to lead,  in order to understand the change
      in T cell immunity of occupational lead-exposed workers. METHODS: The CDR3 of TCR
      Vbeta 24 subfamily genes was amplified in peripheral blood mononuclear cells
      (PBMC) from 6 lead-exposed workers and 6 healthy individuals using RT-PCR,  the
      positive PCR products were further subjected by genescan analysis to identify T
      cell clonality. RESULTS: All 24 TCR Vbeta subfamilies were detected in PBMC from
      6 healthy individuals which all have polyclonal patterns. Only 1-7 Vbeta
      subfamilies could be identified in lead-exposed workers. In detected TCR Vbeta
      subfamilies,  almost oligoclonal and biclonal patterns which mainly in Vbeta1 and
      Vbeta16. CONCLUSION: The restricted expression and clonal expansion of TCR Vbeta
      subfamily have been found in occupational lead-exposed workers,  it may have some
      relationship with lead toxicity damage to the immune function.

PMID- 22152817
TI  - [Mouse anti-human CXCR3 mAb preparation and its biological function].
AB  - AIM: Obtain hybridoma cell line with continuing expression of mouse anti-human
      CXCR3 mAb,  investigate expression characteristics of human CXCR3 and how CXCR3
      signal transduction function on L929-huCXCR3 and colon carcinoma cell lines
      transfer and growth. METHODS: Taking L929-huCXCR3 cell with high expression of
      human CXCR3 membrane molecule as immunogen to immunize BALB/c mouse,  we fused
      immunized mouse spleen cell with myeloma cell Sp2/0 of its same germ line,  then
      used L929-huCXCR3 as screening cell and empty vector transfected cell L929-mock
      as negative control. Obtained hybridoma cell line with continuing secretion of
      anti-human CXCR3 mAb through flow cytometry. We used Ig subclass type rapid
      qualitation indicator paper method and indirect immunofluorescence to identify
      obtained hybridoma cell line and mAb,  indirect immunofluorescence to analyze
      CXCR3 expression on tumor cell surface,  Transwell isolation cabin to assess
      effect on L929-huCXCR3 and colon carcinoma cell line Colo205,  HCT116 and HT29
      migration by mAb,  MTT method to analyze how mAb function on colon carcinoma cell
      line Colo205 proliferation. RESULTS: Obtained a hybridoma cell line with
      continuing secretion of mouse anti-human CXCR3 mAb,  named 9B5. According to
      rapid qualitation test paper analysis,  light chain of the mAb  was   chain and
      heavy chain is IgG1 subclass. Indirect immunofluorescence and flow cytometry
      results show that the mAb can recognize CXCR3 molecules on the surface of
      activated T lymphocyte and colon carcinoma cell line Colo205,  HCT116 and HT29
      cell. mAb 9B5 can inhibit oriented migration of L929-huCXCR3 cells,  colon
      carcinoma cell line Colo205, HCT116 and HT29 cell,  it can also inhibit Colo205
      growth promotion effect by IP-10. CONCLUSION: Successfully obtain a hybridoma
      cell line with continuing secretion of mouse anti-human CXCR3 mAb,  which has
      laid material foundation on investigation of CXCR3 expression characteristics and
      CXCR3 signal transduction function on tumor growth and migration. It is
      prospective to create a new way and a new drug for treatment of tumor metastasis.

PMID- 22152818
TI  - [Preparation of monoclonal antibody against Pfs25 protein and establishment of
      double antibody sandwich ELISA method].
AB  - AIM: To prepare the monoclonal antibody (mAb)against Pfs25 protein of Plasmodium
      falciparum, and establish the method of sandwich ELISA for detecting the Pfs25 
      protein. METHODS: Pfs25 protein the recombinant expressed by Pichia pastoris was
      purified. The purified Pfs25 protein as the antigen was used to immune the BALB/c
      mice,  The secreting specific mAb positive cell strains, which were prepared by
      hybridizing the Sp2/0 myeloma cell and the spleen cell from immunized mice, were
      detected by indirect ELISA method. The ascites of mAb were collected from
      immunization F1 mice, and their biological properties were identified by indirect
      ELISA. The anti-Pfs25 antibody was labeled by Horseradish Peroxidase (HRP),  the
      sandwich ELISA method to detect Pfs25 protein was established based on the anti
      Pfs25 mAb  4B7 and 1B4 as coating and enzyme antibody,  respectively. RESULTS:
      Three hybridoma cell lines secreting mAb against Pfs25 protein have been selected
      from the antibody positive hybridizing cells. The two of them have a better
      stability and specificity. The sandwich ELISA method detecting Pfs25 protein was
      established. Its detecte range was 0.07-1  mg/mL , and its sensitivity was 41.6
      ng/mL. CONCLUSION: The anti-Pfs25 mAb are  successfully prepared and the double
      antibody sandwich ELISA method detecting Pfs25 protein  is established. Our study
      lay a foundation of developing transmission-blocking malaria vaccine with Pfs25
      protein as antigen.

PMID- 22152819
TI  - [Biological activity of purificated swine XCL1 protein and preparation of its
      polyclonal antibody].
AB  - AIM: To obtain purificated his-XCL1 recombinant protein of porcine in vitro and
      prepare the associated polyclonal antibody; To study how the recombinant protein
      affects on lymphocytes proliferation. METHODS: Purify the recombinant protein
      using HiTrap(TM); Chelating HP chromatographic column;  Check the purified
      product using SDS-PAGE; Detect the expression of the recombinant protein using
      Western blot; Immunize the experimental animals with the purified fusion protein
      to prepare the serum containing the associated polyclonal antibody. The serum
      will then undergo double immnodiffusion test and indirect ELISA test to determine
      the polyclonal antibody titer. Then,  test the condition of lymphocytes
      proliferation by MTT. RESULTS: Single target strip could be seen under conducting
      the SDS-PAGE electrophoresis when the concentration of the binding buffer is 40
      mmol/L and the concentration of the elution buffer is 500 mmol/L;  Western blot
      test showed that the recombinant protein could be successfully expressed;  Double
      immunodiffusion test showed the antigen-antibody binding ratio to be 1:8,  and
      the titre of antibodies was 1:12 800 detected by indirect ELISA. The result of
      MTT showed that both the native XCL1 and the recombinant protein could stimulate
      lymphocytes proliferation,  and this stimulating effect could be effectively
      blocked by the polyclonal antibody we prepared. CONCLUSION: To conclude,  this
      recombinant protein has biological activity and this research can provide basic
      material for further investigation of the function of XCL1 in swine.

PMID- 22152820
TI  - [Imbalance of Th17/Treg cell ratio in peripheral blood of patients with nasal
      polyposis and its clinical significance].
AB  - AIM: To observe the distribution of Th17 cells and Foxp3(+);CD4(+);CD25(+);
      regulatory T cells in peripheral blood of patients with nasal polyposis(NP) and
      their correlation with clinical patients' condition,  and to explore the role of
      Th17/Treg cell ratio imbalance in pathogenesis of nasal polyposis and
      significance. METHODS: The frequencies of Th17 cells and Treg cells were
      determined in 46 patients with NP and 10 controls by flow cytometry. The 46
      patients were divided into two groups according to endoscopy score and CT score: 
      the 1 group (endoscopy score:  2-8 scores;  CT score:  3-10 scores,  n=23) and
      the 2 group (endoscopy score:  8-12 scores;  CT score:  10-19 scores,  n=23).
      RESULTS: Th17 cells were significantly higher in the blood of patients with NP
      compared with the control group (P<0.01),  and the percentage was higher in the 2
      group than the 1 group (P<0.05). The frequency of Treg cells was significantly
      decreased in patients with NP compared to the control group (P<0.01),  whereas
      the difference between two groups was not significant. The ratio of Th17/Treg
      cells was highest in the 2 group (P<0.01),  lower in the 1 group (P<0.01) and
      lowest in control subjects,  and the differences were also significant between
      two groups (P<0.05). Furthermore,  it was confirmed that the ratio of Th17/Treg
      positively correlated with endoscopy score and CT score (P<0.01). CONCLUSION: The
      imbalance of Th17/Treg cell ratio characterized by increased Th17 cells and
      decreased Treg cells exists in peripheral blood of NP patients and may play an
      important role in the onset and development of NP. The degree of Th17/Treg cell
      imbalance may associate with clinical presentation.

PMID- 22152821
TI  - An in-patient model for positive airway pressure desensitization: a report of 2
      pediatric cases.
AB  - Application of positive airway pressure is frequently indicated in pediatric
      patients with a diagnosis of obstructive sleep apnea. Adherence to equipment use
      is often less than optimal and can be more challenging when working with children
      with special needs. An in-patient protocol  was designed utilizing various
      techniques and strategies from the medical adherence literature and applied to 2
      cases. This protocol utilizes specialists from various disciplines, including
      respiratory therapists, psychologists, physicians, nurses, and child life
      therapists, as well as parental  involvement. This paper outlines this protocol
      using 2 case studies. Both patients successfully used their equipment for greater
      than 4 hours at night by the end of their hospital stay of 4 days and maintained
      or advanced these gains at follow-up. These 2 cases suggest that more research
      should  be conducted to further evaluate the effectiveness of similar programs.

PMID- 22152822
TI  - Spatio-temporal patterns of distribution of West Nile virus vectors in eastern
      Piedmont Region, Italy.
AB  - BACKGROUND: West Nile Virus (WNV) transmission in Italy was first reported in
      1998 as an equine outbreak near the swamps of Padule di Fucecchio, Tuscany. No
      other cases were identified during the following decade until 2008, when horse
      and human outbreaks were reported in Emilia Romagna, North Italy. Since then, WNV
      outbreaks have occurred annually, spreading from their initial northern foci
      throughout the country. Following the outbreak in 1998 the Italian public health
      authority defined a surveillance plan to detect WNV circulation in birds, horses
      and mosquitoes. By applying spatial statistical analysis (spatial point pattern
      analysis) and models (Bayesian GLMM models) to a longitudinal dataset on the
      abundance of the three putative WNV vectors [Ochlerotatus caspius (Pallas 1771),
      Culex pipiens (Linnaeus 1758) and Culex modestus (Ficalbi 1890)] in eastern
      Piedmont, we quantified their abundance and distribution in space and time and
      generated prediction maps outlining the areas with the highest vector
      productivity and potential for WNV introduction and amplification. RESULTS: The
      highest abundance and significant spatial clusters of Oc. caspius and Cx.
      modestus were in proximity to rice fields, and for Cx. pipiens, in proximity to
      highly populated urban areas. The GLMM model showed the importance of weather
      conditions and environmental factors in predicting mosquito abundance. Distance
      from the preferential breeding sites and elevation were negatively associated
      with the number of collected mosquitoes. The Normalized Difference Vegetation
      Index (NDVI) was positively correlated with mosquito abundance in rice fields
      (Oc. caspius and Cx. modestus). Based on the best models, we developed prediction
      maps for the year 2010 outlining the areas where high abundance of vectors could
      favour the introduction and amplification of WNV. CONCLUSIONS: Our findings
      provide useful information for surveillance activities aiming to identify
      locations where the potential for WNV introduction and local transmission are
      highest. Such information can be used by vector control offices to stratify
      control interventions in areas prone to the invasion of WNV and other mosquito
      transmitted pathogens.

PMID- 22152824
TI  - Commissioning maternity care: little room for manoeuvre?

PMID- 22152825
TI  - Funding for social care: the continuing conundrum.

PMID- 22152826
TI  - From cottage industry to post-industrial care? The King's Fund report on quality
      in general practice.

PMID- 22152827
TI  - Electronic health records: research into design and implementation.

PMID- 22152829
TI  - 'One for all' concerns regarding NICE antibiotic guidelines on suspected
      bacterial meningitis!

PMID- 22152830
TI  - Methadone keeps people alive.

PMID- 22152831
TI  - Ubi Scientia in the midst of the cosy cardigans of Caritas?

PMID- 22152832
TI  - Missed opportunities for diabetes prevention: post-pregnancy follow-up of women
      with gestational diabetes mellitus in England.
AB  - BACKGROUND: Women with gestational diabetes mellitus (GDM) should be followed-up
      to exclude ongoing diabetes and for prevention of type 2 diabetes. The National
      Institute for Health and Clinical Excellence (NICE) diabetes in pregnancy
      guideline recommends checking fasting plasma glucose (FPG) at 6 weeks postpartum
      (short term), and annually thereafter (long term). AIM: To examine the reported
      practice regarding GDM follow-up. DESIGN AND SETTING: Nationwide postal survey in
      England 2008-2009. METHOD: Questionnaires were distributed to a consultant
      diabetologist and obstetrician in all maternity units, and to a random sample of
      general practices (approximately 1 in 5). RESULTS: Response rates were: 60%
      (915/1532) GPs, 93% (342/368) specialists; 80% of GPs and 98% of specialists
      reported women with GDM had short-term follow-up. More GPs (55%) than specialists
      (13%) used a FPG test to exclude ongoing diabetes; 26% of GPs versus 89% of
      specialists thought the hospital was responsible for ordering the test. Twenty
      per cent of GPs had difficulty in discovering women had been diagnosed with GDM
      in secondary care. Seventy-three per cent of specialists recommended long-term
      follow-up; only 39% of GPs recalled women with GDM for this. A minority of GPs
      and specialists had joint follow-up protocols. CONCLUSION: Follow-up of GDM in
      England diverged from national guidance. Despite consensus that short-term follow
      up occurred, primary and secondary care doctors disagreed about the tests and
      responsibility for follow-up. There was lack of long-term follow-up. Agreement
      about the NICE guideline, its promotion and effective implementation by primary
      and secondary care, and the systematic recall of women with GDM for long-term
      follow-up is required.

PMID- 22152833
TI  - Screening for sickle cell and thalassaemia in primary care: a cost-effectiveness
      study.
AB  - BACKGROUND: Haemoglobinopathies, including sickle cell disease and thalassaemia
      (SCT), are inherited disorders of haemoglobin. Antenatal screening for SCT rarely
      occurs before 10 weeks of pregnancy. AIM: To explore the cost-effectiveness of
      offering SCT screening in a primary care setting, during the pregnancy
      confirmation visit. DESIGN AND SETTING: A model-based cost-effectiveness analysis
      of inner-city areas with a high proportion of residents from ethnic minority
      groups. METHOD: Comparison was made of three SCT screening approaches: 'primary
      care parallel' (primary care screening with test offered to mother and father
      together); 'primary care sequential (primary care screening with test offered to
      the mother and then the father only if the mother is a carrier); and 'midwife
      care' (sequential screening at the first midwife consultation). The model was
      populated with data from the SHIFT (Screening for Haemoglobinopathies In First
      Trimester) trial and other sources. RESULTS: Compared to midwife care, primary
      care sequential had a higher NHS cost of L34,000 per 10,000 pregnancies (95%
      confidence interval [CI] = L15,000 to L51,000) and an increase of 2623 women
      screened (95% CI: 1359 to 4495), giving a cost per additional woman screened by
      10 weeks of L13. Primary care parallel was dominated by primary care sequential,
      with both higher costs and fewer women screened. CONCLUSION: The policy judgement
      is whether an earlier opportunity for informed reproductive choice has a value of
      at least L13. Further work is required to understand the value attached to
      earlier informed reproductive choices.

PMID- 22152834
TI  - Time for a national undergraduate curriculum for primary care.

PMID- 22152836
TI  - The tortoise and the hare.

PMID- 22152835
TI  - Postnatal care: development of a psychometric multidimensional satisfaction
      questionnaire (the WOMBPNSQ) to assess women's views.
AB  - BACKGROUND: Postnatal care is the neglected area of pregnancy care, despite
      repeated calls to improve it. Changes would require assessment, which should
      include women's views. No suitable satisfaction questionnaire exists to enable
      this. AIM: To develop a multidimensional psychometric postnatal satisfaction self
      completion instrument. SETTING: Ten maternity services in south west England from
      2006-2009. METHOD: Sources for questions were literature review, fieldwork, and
      related published instruments. Principal components analysis with varimax
      rotation was used to develop the final WOMen's views of Birth Postnatal
      Satisfaction Questionnaire (WOMBPNSQ) version. Validity and internal reliability
      were assessed. Questionnaires were mailed 6-8 weeks postnatally (with one
      reminder). RESULTS: The WOMBPNSQ comprises 36 seven-point Likert questions (13
      dimensions including general satisfaction). Of 300 women, 166 (55.3%) replied; of
      these 155 (95.1 %) were white, 152 (93.8%) were married or cohabiting, 135
      (81.3%) gave birth in a consultant unit, 129 (78.6%) had a vaginal delivery; and
      100 (60.6%) were multiparous. The 12 specific dimensions were: support from
      professionals or partner, or social support; care from GP and health visitor;
      advice on contraception, feeding baby, the mother's health; continuity of care;
      duration of inpatient stay; home visiting; pain after birth. These have internal
      reliability (Cronbach's alpha varying from 0.624 to 0.902). Various demographic
      and clinical characteristics were significantly associated with specific
      dimensions. CONCLUSION: WOMBPNSQ could be used to assess existing or planned
      changes to maternity services or as a screening instrument, which would then
      enable in-depth qualitative assessment of areas of dissatisfaction. Its
      convergent validity and test-retest reliability are still to be assessed but are
      an improvement upon existing postnatal satisfaction questionnaires.

PMID- 22152837
TI  - Professional growth of trainees: applying teacher training models to the training
      of GPs.
AB  - Study of professional growth is useful for reflective purposes at any time during
      a career. The concept of known knowns and unknowns with a training twist can be
      used to summarise the overall stages of any trainee. At the start of vocational
      training the trainee does not know what they do not know, they have not yet
      recognised how much they have to learn. This happens in the second stage (that
      could be equated to survival) when they begin to understand the vast array of
      skills they must develop to make it look easy. With time and practice they will
      reach the point where they know what they have to do--not always getting it right
      but then who does? Finally, and it is particularly important that trainers
      recognise this, an individual will reach the point where everything is so
      automatic they are no longer aware of the intricacies of the skills they have
      acquired. This is where most trainers, both for teachers and GPs, find themselves
      and this can be frustrating for both trainee and trainer as they find they are
      unable to communicate effectively. A good trainer will spend time dissecting and
      'unlearning' their skills so they are able to teach their trainees successfully.
      Trainees, meanwhile, must realise that, one day, they will have their own unknown
      knowns, but they cannot expect it to happen overnight or without substantial
      effort. In moving forward from our training it is how we deal with repeated
      survival stages that determines if we can keep doing the job, it is how we deal
      with the plateau that determines if we will be any good at it--effective on-the
      job training leads to lifelong on-the-job learning.

PMID- 22152838
TI  - General practice and the Foundation Programme.

PMID- 22152840
TI  - Another message from America: nutz!

PMID- 22152842
TI  - Persistent pain: not a medically unexplained symptom.

PMID- 22152843
TI  - Patient feedback in revalidation: an exploratory study using the consultation
      satisfaction questionnaire.
AB  - BACKGROUND: Revalidation is the UK process for the review of doctors to ensure
      they are fit to practise. Revalidation will include patient feedback. AIM: To
      investigate the role of patient feedback on GPs' consultations in revalidation.
      DESIGN AND SETTING: Cross-sectional survey of patients consulting 171 GPs.
      METHOD: A total of 6433 patients aged 16 years or over completed the consultation
      satisfaction questionnaire (CSQ). Generalisability analysis was undertaken, scale
      scores calculated, and outliers identified using two and three standard
      deviations from the mean as control limits. Comments made by patients were
      categorised into positive, neutral, or negative. RESULTS: After averaging each
      scale for each doctor, mean scores (standard deviation), out of a possible score
      of 100, were: general satisfaction 78.1 (7.2); professional care 82.1 (6.1);
      relationship 71.2 (7.1); perceived time 65.7 (7.6). A D-study (which enables
      estimation of the reliability from 0-1 of the CSQ scores for different numbers of
      responders for each doctor), indicated that ratings by 19 patients would achieve
      a generalisability coefficient of 0.80 for the combined score. Fifteen GPs had
      one or more scale scores below two standard deviations of the mean. Comments were
      more often negative for GPs with scores below two standard deviations of the
      mean. CONCLUSION: Most patients of most GPs are satisfied with their experience
      of consultations, and ways to make patient feedback formative for these doctors
      is required. For a few GPs, most patients report some dissatisfaction. Patient
      feedback may identify doctors who need educational support and possibly
      remediation, but agreed questionnaire score thresholds are required, and
      agreement is needed on the weight to be attached to patient experience in
      comparison with other aspects of performance.

PMID- 22152844
TI  - Persistent pain: the need for a cooperative approach.

PMID- 22152845
TI  - Tips for GP trainees working in acute medicine.

PMID- 22152846
TI  - Motivation and satisfaction in GP training: a UK cross-sectional survey.
AB  - BACKGROUND: Recruitment to general practice has had periods of difficulty, but is
      currently going through a phase of relative popularity in the UK. AIM: To explore
      motivators for career choice and career satisfaction among UK GP trainees and
      newly qualified GPs. DESIGN AND SETTING: Cross-sectional web-based questionnaire
      of GP trainees and GPs within the first 5 years of qualification in the UK.
      METHOD: All 9557 UK GP trainees and 8013 GPs who were within the first 5 years of
      qualification were invited to participate by email. Further publicity was
      conducted via general practice publications and the internet. RESULTS: Overall,
      there were 2178 responses to the questionnaire (12.4% response rate, 61.5% women,
      61.8% trainees). Levels of satisfaction were high, with 83% of responders stating
      that they would choose to be a doctor again; of these, 95% would choose to be a
      GP again. The most frequently cited reason for choosing general practice was
      'compatibility with family life', which was chosen by 76.6% of women and 63.2% of
      men (P<0.001). Other reasons given were: 'challenging medically diverse
      discipline' (women 59.8%, men 61.8%, P = 0.350), 'the one-to-one care general
      practice offers' (women 40.0%, men 41.2%, P = 0.570), 'holistic approach' (women
      41.4%, men 30.1%, P<0.001), 'autonomy and independence' (women 18.0%, men 34.8%,
      P<0.001), 'communication' (women 20.6%, men 12.2%, P<0.001), 'negative
      experiences in hospital' (women 12.8%, men 9.8%, P= 0.036), and 'good salary'
      (women 7.8%, men 14.9%, P<0.001). CONCLUSION: The most important reason for both
      women and men choosing general practice as a career in the UK is its
      compatibility with family life. As such, changes to UK primary care that decrease
      family compatibility could negatively impact on recruitment.

PMID- 22152847
TI  - Opening the black box: the patient mix of GP trainees.
AB  - BACKGROUND: The variety of health problems (patient mix) that medical trainees
      encounter is presumed to be sufficient to master the required competencies. AIM:
      To describe the patient mix of GP trainees, to study differences in patient mix
      between first-year and third-year GP trainees, and to investigate differences in
      exposure to sex-specific diseases between male and female trainees. DESIGN AND
      SETTING: Prospective cohort study in Dutch primary care. METHOD: During a 6-month
      period, aggregated data about International Classification of Primary Care
      diagnosis codes, and data on the sex and age of all contacts were collected from
      the electronic patient record (EPR) system. RESULTS: Seventy-three trainees
      participated in this study. The mean coding percentage was 86% and the mean
      number of face-to-face consultations per trimester was 450.0 in the first year
      and 485.4 in the third year, indicating greater variance in the number of patient
      contacts among third-year trainees. Diseases seen most frequently were:
      musculoskeletal (mean per trimester = 89.2 in the first year/91.0 in the third
      year), respiratory (98.2/92.7) and skin diseases (89.5/96.0). Least often seen
      were diseases of the blood and blood-forming organs (5.3/7.2), male genital
      disorders (6.1/7.1), and social problems (4.3/4.2). The mean number of chronic
      diseases seen per trimester was 48.0 for first-year trainees and 62.4 for third
      year trainees. Female trainees saw an average of 39.8 female conditions per
      trimester--twice as many as male trainees (mean = 21.3). CONCLUSION: Considerable
      variation exists trainees in the number of patient contacts. Differences in
      patient mix between first- and third-year trainees seem at least partly related
      to year-specific learning objectives. The use of an EPR-derived educational
      instrument provides insight into the trainees' patient mix at both the group and
      the individual level. This offers opportunities for GP trainers, trainees, and
      curriculum designers to optimise learning when exposure may be low.

PMID- 22152848
TI  - Nurse case management and general practice: implications for GP consortia.
AB  - BACKGROUND: Case management is widely promoted as a means of ensuring continuity
      of care, improving patient outcomes, and achieving efficient management of
      resources. Community matrons have been introduced recently as specialists in the
      case management of patients with multiple complex problems. AIM: To understand
      how nurse case managers are seen by GPs and NHS managers. SETTING: (1) Telephone
      interviews with 41 community nurse managers recruited from 10 English strategic
      health authorities and two Welsh health boards; (2) face-to-face interviews with
      12 nurse case managers, 12 GPs and five NHS community service managers in three
      study sites with different population and practitioner characteristics. METHOD:
      Semi-structured individual interviews, by telephone or face to face. RESULTS:
      Attitudes among GPs to nurse case managers were shaped by perceptions of the
      quality of community nursing on the one hand and the perceived benefit of case
      management as a method of reducing hospital use on the other. The dominant mood
      was scepticism about the ability of nurse case managers to reduce hospital
      admissions. Community matrons were seen as staff who were imposed on local health
      services, sometimes to detrimental effect. CONCLUSION: The introduction of case
      management and community matrons may disrupt existing communities of practice and
      be perceived negatively, at least in areas where good working relationships
      between nurses and GPs have developed. Commissioners should be aware of the
      potential resistance to changes in skill mix and role in nursing services, and
      promote innovation in ways that minimise disruption to functional communities of
      practice.

PMID- 22152849
TI  - The Quality and Outcomes Framework and self-management dialogue in primary care
      consultations: a qualitative study.
AB  - BACKGROUND: Two key elements to improve the quality of care for people with long
      term conditions in primary care are improved clinical information systems to
      support delivery of evidence-based care, and enhanced self-management support.
      Although both elements are viewed as necessary, their interaction is not well
      understood. AIM: To explore the use of computer-based 'disease management'
      templates and their relevance to self-management dialogue within clinical
      encounters. DESIGN AND SETTING: Qualitative study of general practices located in
      three primary care trusts in the north of England. METHOD: A qualitative mixed
      methods study was conducted that included comparative analysis of (1)
      observations of general practice consultations (n = 86); and (2) interviews with
      health professionals in general practice (n = 17). RESULTS: The analysis
      suggested that use of the computer templates reinforced a checklist approach to
      consultations, which included professionals working through several self
      management topics framed as discrete behaviours. As a consequence, conversation
      tended to become focused on the maintenance of the professional-patient
      relationship at the expense of expansion in self-management dialogue. The
      computer templates also shaped how patient-initiated self-management dialogue was
      managed when it arose, with a shift towards discussion around medical agendas.
      CONCLUSION: In order to enhance the management of long-term conditions in primary
      care, the design and implementation of clinical information systems to improve
      evidence-based care need to take into account their potential impact on
      supporting self-management.

PMID- 22152850
TI  - Does a decision aid help physicians to detect chronic obstructive pulmonary
      disease?
AB  - BACKGROUND: Numerous decision aids have been developed recently, but the value
      they add above that of the initial clinical assessment is not well known. AIM: To
      quantify whether a formal decision aid for chronic obstructive pulmonary disease
      (COPD) adds diagnostic information, above the physician's clinical assessment.
      DESIGN AND SETTING: Subanalysis of a diagnostic study in Dutch primary care.
      METHOD: Sixty-five primary care physicians included 357 patients who attended for
      persistent cough and were not known to have COPD. The physicians estimated the
      probability of COPD after short history taking and physical examination. After
      this, the presence or absence of COPD was determined using results of extensive
      diagnostic work-up. The extent to which an 8-item decision aid for COPD, which
      included only symptoms and signs, added diagnostic value above the physician's
      estimation was quantified by the increase of the area under the receiver
      operating characteristic curve (ROC area), and the improvement in diagnostic risk
      classification across two classes: 'low probability of COPD' (<20%) and 'possible
      COPD' (>=20%). RESULTS: One hundred and four patients (29%) had COPD. Adding the
      decision aid to the clinical assessment increased the ROC area from 0.75 (95%
      confidence interval [CI] = 0.70 to 0.81) to 0.84 (95% CI = 0.80 to 0.89)
      (P<0.005), and improved the diagnostic risk classification of the patients, such
      that 35 fewer patients needed spirometry testing and eight fewer COPD cases were
      missed. CONCLUSION: A short decision aid for COPD added diagnostic value to the
      physician's clinical assessment.

PMID- 22152851
TI  - Ear wax removal interventions: a systematic review and economic evaluation.

PMID- 22152852
TI  - The 2011 EBCTCG polychemotherapy overview.

PMID- 22152853
TI  - Comparisons between different polychemotherapy regimens for early breast cancer:
      meta-analyses of long-term outcome among 100,000 women in 123 randomised trials.
AB  - BACKGROUND: Moderate differences in efficacy between adjuvant chemotherapy
      regimens for breast cancer are plausible, and could affect treatment choices. We
      sought any such differences. METHODS: We undertook individual-patient-data meta
      analyses of the randomised trials comparing: any taxane-plus-anthracycline-based
      regimen versus the same, or more, non-taxane chemotherapy (n=44,000); one
      anthracycline-based regimen versus another (n=7000) or versus cyclophosphamide,
      methotrexate, and fluorouracil (CMF; n=18,000); and polychemotherapy versus no
      chemotherapy (n=32,000). The scheduled dosages of these three drugs and of the
      anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard
      CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios
      (RRs) are reported. FINDINGS: In trials adding four separate cycles of a taxane
      to a fixed anthracycline-based control regimen, extending treatment duration,
      breast cancer mortality was reduced (RR 0.86, SE 0.04, two-sided significance
      [2p]=0.0005). In trials with four such extra cycles of a taxane counterbalanced
      in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane
      dosage, there was no significant difference (RR 0.94, SE 0.06, 2p=0.33). Trials
      with CMF-treated controls showed that standard 4AC and standard CMF were
      equivalent (RR 0.98, SE 0.05, 2p=0.67), but that anthracycline-based regimens
      with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF)
      were superior to standard CMF (RR 0.78, SE 0.06, 2p=0.0004). Trials versus no
      chemotherapy also suggested greater mortality reductions with CAF (RR 0.64, SE
      0.09, 2p<0.0001) than with standard 4AC (RR 0.78, SE 0.09, 2p=0.01) or standard
      CMF (RR 0.76, SE 0.05, 2p<0.0001). In all meta-analyses involving taxane-based or
      anthracycline-based regimens, proportional risk reductions were little affected
      by age, nodal status, tumour diameter or differentiation (moderate or poor; few
      were well differentiated), oestrogen receptor status, or tamoxifen use. Hence,
      largely independently of age (up to at least 70 years) or the tumour
      characteristics currently available to us for the patients selected to be in
      these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage
      anthracycline-based regimens (not requiring stem cells) reduced breast cancer
      mortality by, on average, about one-third. 10-year overall mortality differences
      paralleled breast cancer mortality differences, despite taxane, anthracycline,
      and other toxicities. INTERPRETATION: 10-year gains from a one-third breast
      cancer mortality reduction depend on absolute risks without chemotherapy (which,
      for oestrogen-receptor-positive disease, are the risks remaining with appropriate
      endocrine therapy). Low absolute risk implies low absolute benefit, but
      information was lacking about tumour gene expression markers or quantitative
      immunohistochemistry that might help to predict risk, chemosensitivity, or both.
      FUNDING: Cancer Research UK; British Heart Foundation; UK Medical Research
      Council.

PMID- 22152854
TI  - Wnt signaling and telomerase activation of hepatoblastoma: correlation with
      chemosensitivity and surgical resectability.
AB  - PURPOSE: Recently, it became apparent that telomerase directly modulated Wnt
      signaling as a cofactor in a beta-catenin transcriptional complex. In this study,
      we investigated Wnt/beta-catenin signaling and telomerase activation in
      hepatoblastoma (HBL). METHODS: Tumors derived from 56 HBL cases treated with the
      Japanese Study Group for Pediatric Liver Tumors (JPLT) Protocol-2 were analyzed
      for oncogenic mutations (missense mutations and interstitial deletions in the
      third exon) of the CTNNB1 gene-encoding beta-catenin and for the expression
      levels of telomerase reverse transcriptase (TERT). RESULTS: Oncogenic mutations
      of CTNNB1 were detected in 42 cases (75%). The expression levels of TERT were
      significantly higher in 14 cases without mutation (P < .05) and in 8 cases with
      metastasis (P < .01). Interestingly, Wnt/beta-catenin target genes were
      significantly activated in the tumors without mutations (P = .013). In cases with
      mutations, preoperative chemotherapy was more effective (P = .008), and complete
      resection rate was higher (P = .034). Consequently, 2 patients with mutations and
      4 patients without mutations died of disease (P = .013). High expression of TERT
      was detected in all tumors of these dead patients. CONCLUSIONS: Wnt/beta-catenin
      signaling in the HBLs without CTNNB1 mutations was activated by high expression
      of TERT. The clinical courses in HBLs without CTNNB1 mutations seemed to be
      unfavorable because of chemoresistance and low rates of resectability.

PMID- 22152855
TI  - Correlation between the number of segmental chromosome aberrations and the age at
      diagnosis of diploid neuroblastomas without MYCN amplification.
AB  - BACKGROUND: In neuroblastomas (NBs) without MYCN amplification, segmental
      chromosome aberrations SCAs such as 1p loss, 11q loss, and 17q gain have been
      suggested to be associated with the prognosis of the patients. We assessed the
      correlation between the number of SCAs and other biological factors in primary
      NBs samples. METHOD: The status of SCAs in 54 primary NBs samples was analyzed
      using the single-nucleotide polymorphism (SNP) array (Human CMV370-Duo; Illumina,
      San Diego, CA). The status of MYCN amplification was determined by an SNP array
      and the fluorescence in situ hybridization method. The DNA ploidy was determined
      by flow cytometry. RESULTS: Nine of 54 samples showed MYCN amplification. All 9
      samples with MYCN amplification and 20 of 45 samples without MYCN amplification
      showed diploidy/tetraploidy, and the other 25 samples without MYCN amplification
      showed aneuploidy. The most frequent SCAs were 17q gain (26/54; 48.1%) and 11q
      loss (16/54; 29.6%), followed by 1p loss (15/54; 27.8%). The number of SCAs in
      diploidy/tetraploidy NBs without MYCN amplification (7.00 +/- 4.67) was higher
      than that in NBs with MYCN amplification (4.78 +/- 2.82) and in aneuploid NBs
      (1.64 +/- 2.78) (P < .05). In diploid/tetraploid NBs without MYCN amplification,
      there was a significant difference between an age at diagnosis less than 12
      months (n = 7) and over 12 months (n = 13) (4.14 +/- 3.63 vs 8.54 +/- 4.54; P =
      .04). Moreover, the number of SCAs correlated with the age at diagnosis in
      diploid/tetraploid samples without MYCN amplification (r = 0.70, P = .0006). In
      NBs with MYCN amplification, the number of SCAs did not correlate with the age at
      diagnosis. CONCLUSION: The number of SCAs significantly increased in proportion
      to age at diagnosis in diploid/tetraploid NBs without MYCN amplification. The
      increase in the number of these SCAs may play an important role in the prognosis
      of patients without MYCN amplification over 12 months of age.

PMID- 22152856
TI  - Expression of Wilms tumor 1 gene in a variety of pediatric tumors.
AB  - BACKGROUND/PURPOSE: Wilms tumor 1 (WT1) gene is overexpressed in many types of
      neoplasms, thus suggesting that WT1 has oncogenic properties. Therefore, WT1 is a
      molecular target for cancer therapy. The objectives of this study were to
      evaluate the WT1 gene expression in various pediatric tumors and to elucidate
      that WT1 can be a target of cancer therapy in pediatric malignancies. PATIENTS
      AND METHODS: The expression of WT1 protein was examined in 60 cases of primary
      pediatric tumors. The levels of WT1 messenger RNA (mRNA) expression were examined
      by a quantitative real-time reverse transcriptase polymerase chain reaction
      analysis in frozen tissue samples from 56 cases with pediatric tumors. RESULTS:
      Immunohistochemical staining revealed that WT1 protein was widely detected in
      pediatric malignancies. The alveolar subtype of rhabdomyosarcoma showed more
      intensive staining than the embryonal subtype. The positive rate of the alveolar
      type was significantly higher than that of the embryonal type. The expression of
      WT1 mRNA in the tumor samples varied widely. However, no significant correlation
      was observed between WT1 mRNA expression and clinical factors. CONCLUSION: The
      WT1 expression was broadly detected in various pediatric neoplasms. These results
      indicate that WT1 may therefore be a potentially useful therapeutic target in
      most of pediatric malignancies.

PMID- 22152858
TI  - Interest in international surgical volunteerism: results of a survey of members
      of the American Pediatric Surgical Association.
AB  - PURPOSE: This study assesses interest in international volunteer work by members
      of the American Pediatric Surgical Association (APSA) and attempts to identify
      demographics, motivations, obstacles, and institutional issues of the
      respondents. METHODS: An online survey service was used to send a 25-question
      survey to all APSA members with email addresses in November 2009. An answer to
      all questions was not required. Written comments were encouraged. RESULTS: The
      survey was sent to 807 members of whom 316 responded, for a response rate of 39%.
      International work had been done previously by 48% of respondents, whereas 95%
      stated that they were interested or perhaps interested in doing so. Most (83%)
      were interested in operating with local surgeons to teach them how to perform
      procedures. Altruism was the chief motivation in 75% of respondents. Primary
      obstacles to doing international work were family obligations and lack of time,
      although 37% stated that a lack of information about volunteer opportunities was
      an issue. A significant number of respondents (48%) stated that their institution
      had no established international collaborations. CONCLUSION: This study suggests
      that there is interest in international volunteerism among many members of APSA.
      Understanding the issues surrounding surgical volunteerism may facilitate
      humanitarian involvement among pediatric surgeons.

PMID- 22152857
TI  - Critical infantile hepatic hemangioma: results of a nationwide survey by the
      Japanese Infantile Hepatic Hemangioma Study Group.
AB  - BACKGROUND: The current survey aimed to describe the clinical features of
      critical infantile hepatic hemangioma (IHH) and the implications of recent
      treatments. MATERIALS AND METHODS: A nationwide survey of critical IHH patients
      treated between 2005 and 2010 was performed in all 117 registered pediatric
      surgical hospitals in Japan. As a result, 19 patients were identified and
      reviewed using a statistical analysis. RESULTS: Abdominal distention (47.4%),
      high-output cardiac failure (47.4%), coagulopathy (42.1%), and respiratory
      distress (31.6%) were the major symptoms. Three patients died (1 of coagulopathy,
      1 of cardiac failure, and 1 of both). An accompanying portovenous shunt was also
      highlighted. Infantile hepatic hemangioma was totally insensitive to steroid
      treatment in 3 (23.1%) of the 13 patients, and 9 (47.4%) of the 19 patients
      required other treatments. Surgical resection and beta-blocker improved the
      hematologic data, whereas hepatic arterial ligation and embolization seemed to
      produce a limited effect. Among the dead patients, several hematologic parameters
      were significantly worse: the thrombocyte count (pretherapeutic: 73,000 vs
      300,000/mm(3), dead vs survivor, respectively [P < .03]; posttherapeutic: 66,000
      vs 388,700/mm(3) [P < .003]) and the prothrombin time (posttherapeutic, 35.0 vs
      12.1 seconds [P < .0001], dead vs survivor, respectively). CONCLUSION: For
      critical IHH cases with steroid-insensitive hematologic disorders, alternative
      treatments including beta-blocker therapy, surgery, and liver transplantation
      should be considered.

PMID- 22152860
TI  - Increase in fetal pulmonary artery diameters during late gestation is a predictor
      of outcome in congenital diaphragmatic hernia with liver herniation.
AB  - AIM: Liver herniation (LH) in congenital diaphragmatic hernia (CDH) may not be a
      reliable prognostic indicator. We measured pulmonary artery (PA) diameters in CDH
      + LH as an alternative. METHODS: Of 41 consecutive cases of prenatally diagnosed
      left-sided CDH treated from 2002 to 2010, 19 had CDH + LH and 22 had CDH - LH.
      Ultrasonography and magnetic resonance imaging were used to assess LH and
      echocardiography to measure PA diameters during the third trimester (fetal; 32-34
      weeks), at birth, and on day 2 of life. RESULTS: In CDH + LH survivors (9/19;
      47%), fetal right PA (RPA) diameters were significantly larger than in
      nonsurvivors (2.58 +/- 0.56 vs 1.82 +/- 0.35 mm; P < .01), but left PA (LPA)
      diameters were not (1.73 +/- 0.38 vs 1.59 +/- 0.22). In survivors, fetal RPA was
      greater than 2 mm in all but one case, and both PA diameters increased
      significantly by birth (RPA, 2.58 +/- 0.56 vs 3.52 +/- 0.54; LPA, 1.73 +/- 0.38
      vs 2.60 +/- 0.40; both P < .01). Final diameters at birth in survivors were at
      least 2.5 and 2.0 mm, respectively. In nonsurvivors, both PAs were significantly
      smaller (RPA, 3.52 +/- 0.54 vs 2.04 +/- 0.31; LPA, 2.60 +/- 0.40 vs 1.68 +/-
      0.18; P < .01), with no observed increase by birth. Survival in CDH - LH was 82%
      (18/22). CONCLUSION: PA diameter appears to be correlated with prognosis in
      infants with CDH + LH.

PMID- 22152859
TI  - Psychosocial and cognitive consequences of major neonatal surgery.
AB  - PURPOSE: To evaluate the long-term quality of life (QOL) of patients who had
      undergone major neonatal surgery, the psychosocial and cognitive consequences of
      neonatal surgical stress were assessed when the patients reached school age.
      MATERIALS AND METHODS: Seventy-two patients who had undergone major neonatal
      surgery were enrolled in this study. Their primary diseases were anorectal
      malformation (ARM) in 27 cases, esophageal atresia (EA) in 23, and congenital
      diaphragmatic hernia (CDH) in 22. Intelligence tests using Wechsler Intelligence
      Scale for Children III (WISC-III) or a developmental test and the Child Behavior
      Checklist were conducted through questionnaires and interviews with clinical
      psychologists. RESULTS: Mental retardation (MR) was apparent in 25% of EA, 20% of
      ARM, and 18% of CDH, significantly higher than the 2% to 3% commonly found in the
      general population. The clinical range (CR) of the Child Behavior Checklist was
      seen in 35% of EA, 59% of ARM, and 38% of CDH, which is also significantly higher
      than the 25% typically seen in the general population. No significant differences
      in MR and CR were seen among the primary diseases. The most important factors
      influencing MR and CR remain to be identified. CONCLUSIONS: To ensure true
      quality of life after neonatal surgical stress, pediatric surgeons must consider
      not only physical assessments but also cognitive, emotional, and psychosocial
      assessments.

PMID- 22152861
TI  - Defining risk for infectious complications on extracorporeal life support.
AB  - BACKGROUND/PURPOSE: Little is known about potentially modifiable risk factors
      associated with infectious complications (IC) acquired during extracorporeal life
      support (ECLS). PATIENTS AND METHODS: The Extracorporeal Life Support
      Organization registry was accessed, and data on patient demographics, run
      characteristics, infections, and outcomes were collected. Patients who developed
      IC while on ECLS were compared to those that did not. Regression analysis was
      performed. Results are expressed as odds ratios, with P < .05 considered
      significant. RESULTS: Infectious complications developed in 10.2% of 38,661
      patients and was associated with increased odds of death. Risk factors for IC
      included increasing age, diagnosis, more remote decade, complications, presence
      of multiple complications, and ECLS mode. The risk of IC increased with the
      number of complications (P < .001). Patients with positive cultures before ECLS
      also had increased odds of IC (OR 2.12, 95% CI 1.92-2.34, P < .001). Those with
      IC were more likely to have cultures grow aggressive organisms (non-lactose
      fermenting gram negative rods, methicillin resistant Staphylococcus aureus, and
      fungi). CONCLUSIONS: Strategies to reduce IC while on ECLS should be aimed at
      prevention of complications and treatment of pre-existing infections. Future
      studies should address whether broader spectrum antibiotic prophylaxis and/or
      empiric coverage for suspected sepsis is indicated in ECLS patients.

PMID- 22152862
TI  - Thoracoscopic segmentectomy for treatment of congenital lung malformations.
AB  - PURPOSE: Congenital lung malformations (CLM) predispose patients to recurrent
      respiratory tract infections and pose a rare risk of malignant transformation.
      Although pulmonary lobectomy is the most common treatment of a CLM, some advocate
      segmental resection as a lung preservation strategy. Our study evaluated lung
      preserving thoracoscopic segmentectomy as an alternative to lobectomy for CLM
      resection. METHODS: We conducted a retrospective review of patients who underwent
      thoracoscopic segmentectomy for CLM from 2007 to 2010. RESULTS: Fifteen patients
      underwent thoracoscopic segmentectomy for CLM. There were five postoperative
      complications: three asymptomatic pneumothoraces and a small air leak that
      resolved without intervention. One patient developed a bronchopulmonary fistula
      requiring thoracoscopic repair. At follow-up, all patients are asymptomatic. One
      patient has a small amount of residual disease on postoperative computed
      tomography (CT), and re-resection has been recommended. CONCLUSIONS:
      Thoracoscopic segmentectomy for CLM is a safe and effective means of lung
      parenchymal preservation. The approach spares larger airway anatomy and has a
      complication rate that is comparable with that of thoracoscopic lobectomy.
      Residual disease can often only be appreciated on postoperative CT scan and may
      require long-term follow-up or reoperation in rare cases. This lung preservation
      technique is best suited to smaller lesions.

PMID- 22152863
TI  - A novel measure for pectus excavatum: the correction index.
AB  - OBJECTIVE: The Haller Index (HI), the standard metric for the severity of pectus
      excavatum, is dependent on width and does not assess the depth of the defect.
      Therefore, we performed a diagnostic analysis to assess the ability of HI to
      separate patients with pectus excavatum from healthy controls compared to a novel
      index. METHODS: After institutional review board approval, computed tomography
      scans were evaluated from patients who have undergone pectus excavatum repair and
      controls. The correction index (CI) used the minimum distance between posterior
      sternum and anterior spine and the maximum distance between anterior spine most
      anterior portion of the chest. The difference between the two is divided by the
      latter (*100) to give the percentage of chest depth the defect represents.
      RESULTS: There were 220 controls and 252 patients with pectus. Mean HI was 2.35,
      and the mean CI was 0.92 for the controls. The mean HI was 4.06, and the mean CI
      was 31.75 in the patients with pectus. In the patients with pectus, HI
      demonstrated a 47.8% overlap with the controls, while there was no overlap for
      CI. CONCLUSIONS: The Haller index demonstrates 48% overlap between normal
      patients and those with pectus excavatum. However, the proposed correction index
      perfectly separates the normal and diseased populations.

PMID- 22152864
TI  - The outcome of conservative treatment for anastomotic leakage after surgical
      repair of esophageal atresia.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical outcome of
      conservative management of anastomotic leakage (AL) after surgical repair for
      esophageal atresia. METHODS: Data from 85 neonates with esophageal atresia who
      underwent surgical correction were retrospectively analyzed. Conservative
      treatment had been adopted for AL. The incidence and severity of postoperative AL
      as well as its effects were analyzed. RESULTS: Among the 85 neonates,
      postoperative AL occurred in 21 (25%) cases, with major leaks in 15 cases and
      minor leaks in 6. The stricture index of the 21 neonates with AL (0.615 +/-
      0.032) was significantly different (P = .008) from that of the 64 neonates
      without leakage (0.509 +/- 0.018). The overall incidence of gastroesophageal
      reflux (GER) was 36%. Esophageal dysmotility and clinically significant
      tracheomalacia were observed in 69 and 7 infants, respectively, of the 80
      surviving patients. The incidence of GER, dysmotility, and tracheomalacia in
      patients with or without AL was similar. The severity of GER in patients with
      different numbers of sessions of dilation was significantly different (P =
      .0015). CONCLUSIONS: Postoperative esophageal AL is effectively treatable by
      conservative methods in most neonates. The occurrence of AL may aggravate the
      severity of esophageal stricture but does not affect the incidence of GER,
      esophageal dysmotility, and tracheomalacia.

PMID- 22152865
TI  - Prenatal repair of myelomeningocele with aligned nanofibrous scaffolds-a pilot
      study in sheep.
AB  - BACKGROUND/PURPOSE: Spinal cord damage in myelomeningocele (MMC) results from
      abnormal cord development and subsequent local trauma. Prenatal surgery prevents
      additional neural injury. However, existing damage is not reversed. Biodegradable
      nanofibrous scaffolds (NSs) promote regeneration of neural tissues. They mimic
      the microtopography of the extracellular matrix and guide tissue formation and
      organization. The purpose of this pilot study was to evaluate the practicality
      and safety of using biodegradable NS as a regenerative device in prenatal MMC
      repair. METHODS: Two fetal lambs underwent a surgically induced MMC defect
      followed by open fetal repair using aligned biodegradable NS. Lambs were killed
      at day 138. Spinal cords were examined for inflammation or fibrosis and stained
      for spinal cord architecture, myelin, and neuron cell bodies. RESULTS: Prenatal
      repair with NS demonstrated technical feasibility. There was no evidence of a
      surrounding inflammatory response or foreign-body reaction to the scaffold.
      CONCLUSION: Biodegradable NS can be used surgically for the prenatal repair of
      MMC in a large animal model and does not appear to elicit an inflammatory or
      fibrotic reaction in fetal tissue. Further studies will determine their potential
      for neural cell infiltration, delivery of growth factors, drugs or stem cells,
      and functional recovery greater than standard repair.

PMID- 22152866
TI  - Synchronized expressions of hepatic stellate cells and their transactivation and
      liver regeneration during liver injury in an animal model of cholestasis.
AB  - BACKGROUND: There is much known about hepatic stellate cells (HSCs) during liver
      injury. However, some aspects remain unclear, such as the natural expression
      levels of HSCs during the days to weeks after liver injury. Does liver
      regeneration start the same time as the injury process? METHODS: Fifty-four male
      Wistar rats aged 7 to 8 weeks, weighing 200 to 320 g each were subjected to bile
      duct ligation (BDL). After surgery, they were killed at different times post-BDL.
      Collagen deposition was analyzed, and immunohistochemical staining of alpha
      smooth muscle actin (alpha-SMA), vimentin, matrix metalloproteinase-2 (MMP-2),
      tissue inhibitor matrix metalloproteinase-1, and proliferating cell nuclear
      antigen antibody (PCNA) was performed to evaluate HSCs and liver regeneration.
      RESULTS: The expression of alpha-SMA was seen as early as day 3 post-BDL, which
      started from peribiliary to perisinusoidal, and was seen throughout the whole
      liver sections on day 28 post-BDL. Similar expression patterns were seen in MMP-2
      staining. The PCNA expression was strongest around the perisinusoidal area. These
      expression patterns were not observed in the sham-operated rats. CONCLUSIONS: The
      activation of HSCs showed a synchronized fibrogenic process and liver
      regeneration from days to weeks after liver injury. Matrix degradation was thus
      found to increase in accordance with chronic liver injury, which thus led to an
      excessive collagen deposition.

PMID- 22152867
TI  - Outcome of modified portal vein anastomosis for recipients with portal vein
      thrombosis or stenosis before living donor liver transplantation.
AB  - BACKGROUND: Portal vein thrombosis (PVT) or stenosis (PVS) often requires
      challenging techniques for reconstruction in living donor liver transplantation
      (LDLT). MATERIALS AND METHODS: A total of 57 LDLTs were performed between October
      1996 and December 2010. There were 16 cases (28%) with PVT/PVS that underwent
      modified portal vein anastomosis (m-PVa). The m-PVa techniques were classified
      into 3 groups: patch graft (Type-1), interposition graft (Type-2), and using huge
      shunt vessels (Type-3). The reconstruction patterns were evaluated with regard to
      age, graft vessels, PV flow, and complication rate. RESULTS: The m-PVas were Type
      1 in 10 cases, Type-2 in 3 cases, and Type-3 in 3 cases. The vessel graft in Type
      1 was the inferior mesenteric vein (IMV) in 8 and the jugular vein in 2 cases,
      whereas the vessel graft in Type-2 was IMV in 2 and the saphenous vein in 1 case;
      in Type-3, the vessel grafts were renoportal, gonadal-portal, and coronary-portal
      anastomoses, respectively. The postoperative PV flow was sufficient in all types
      and slightly higher in Type-3. The postoperative complications occurred in 20% of
      the patients who underwent Type-1, in 33% who underwent Type-2, and in 0% who
      underwent Type-3. CONCLUSION: The m-PVa was effective to overcome the surgical
      difficulty during transplantation. Pretransplant planning for the selection of
      the type of reconstruction is important for recipients with PVT/PVS.

PMID- 22152868
TI  - Clinical characteristics of liver fibrosis in patients with choledochal cysts.
AB  - PURPOSE: The aim of the study was to identify the clinical characteristics and
      outcome of patients with liver fibrosis in choledochal cyst (CC). METHODS: Forty
      patients with CC who underwent liver biopsy were included. Liver fibrosis was
      classified as follows: grade 0, no fibrosis; grade 1, mild fibrosis localized in
      the portal area; grade 2, moderate fibrosis with occasional bridging; and grade
      3, severe fibrosis with diffuse bridging. RESULTS: Fourteen patients (35%) had
      liver fibrosis. Patients in the fibrosis group were significantly younger (1.2 vs
      2.7 years) and had higher total bilirubin (5.3 vs 2.6 mg/dL). Severity of liver
      fibrosis was inversely correlated with age (P = .044). Amylase and lipase in bile
      were significantly lower in the fibrosis group (amylase, 531 vs 15,000 U/L;
      lipase, 783 vs 23,100 U/L). Postoperative serum analysis demonstrated no
      differences between the two groups. Most patients in both groups had normal
      aspartate aminotransferase, alanine aminotransferase, total bilirubin, and gamma
      glutamyl transpeptidase regardless of severity of fibrosis. Postoperative biliary
      complication or cholangiocarcinoma was not found in the fibrosis group.
      CONCLUSIONS: Our data suggest that liver fibrosis is mainly influenced by
      obstructive cholangiopathy rather than refluxed pancreatic secretion. Prognosis
      of patients with CC and liver fibrosis was as good as that of patients without
      fibrosis.

PMID- 22152869
TI  - Bile duct duplication as a cause of distal bowel gas in neonatal duodenal
      obstruction.
AB  - PURPOSE: The aim of this study is to investigate the clinical characteristics of
      cases of duodenal atresia (DA) which present with bowel gas distal to a typical
      double-bubble sign through an anomalous bile duct conduit. METHODS: Medical
      records of 57 neonates with duodenal obstruction (atresia or stenosis),
      presenting with a double-bubble sign and treated at our institute from 1978 to
      2010, were retrospectively reviewed. RESULTS: Thirteen (23%) of 57 neonates
      presented with bowel gas distal to the double-bubble sign. Passage of gas through
      the duodenal stenosis may have occurred in 3 cases, whereas in 9 cases, gas may
      have bypassed the atresia through an anomalous bifurcated bile duct termination
      and through the pancreatic duct from the accessory to the main pancreatic duct in
      one case. A preoperative upper gastrointestinal series was performed in 9 cases,
      and an anomalous bifurcated bile duct conduit was demonstrated in 5 cases. Severe
      and prolonged cholestasis necessitating evaluation for biliary atresia was found
      in 2 patients with anomalous bile duct anatomy. CONCLUSIONS: Neonatal DA
      presenting with distal bowel gas via an anomalous bifurcated bile duct conduit is
      more common than initially thought and occurs more frequently than duodenal
      stenosis. These patients might be at risk for cholestasis, possibly owing to
      duodeno-biliary reflux through the ampulla.

PMID- 22152870
TI  - Visualization of enteric neural crest cell migration in SOX10 transgenic mouse
      gut using time-lapse fluorescence imaging.
AB  - BACKGROUND: Enteric neural crest cells (ENCCs) were labeled with VENUS, an
      enhanced green fluoroscein protein, to record their migration in genetically
      engineered transgenic (SOX10-VENUS) mice. MATERIALS AND METHODS: Pregnant SOX10
      VENUS mice were killed on day 12.5 of gestation. The colorectum was excised from
      each embryo (n = 20) and placed in tissue culture medium. Time-lapse images
      captured using fluorescence microscopy at 10-minute intervals for 3000 minutes
      were compiled into a video to display ENCC migration. RESULTS: At 0 minutes,
      VENUS(+) ENCC were observed to be clustered in the cecum and proximal colon
      (vagal ENCC), and similar cells were also seen in the rectum/sacrum (sacral
      ENCC). After 500 minutes, vagal VENUS(+) ENCC had migrated caudally from the
      proximal colon to the midcolon, reaching the distal colon after 800 minutes.
      Sacral VENUS(+) ENCC had migrated rostrally and transversely by 1250 minutes and
      had integrated with vagal ENCC by 2500 minutes. CONCLUSION: We recorded the
      actual rostral-to-caudal migration of vagal ENCC, caudal-to-rostral migration of
      sacral ENCC, and their integration in the developing mouse hindgut. Such direct
      evidence of ENCC migration may further elucidate understanding of ENCC
      development, thus providing insight into the histopathology of bowel dysmotility
      disorders.

PMID- 22152871
TI  - Long-term effects of transabdominal electrical stimulation in treating children
      with slow-transit constipation.
AB  - AIMS: Transcutaneous electrical stimulation (TES) was used to treat children with
      slow-transit constipation (STC) for 1 to 2 months in a randomized controlled
      trial during 2006 to 2008. We aimed to determine long-term outcomes,
      hypothesizing that TES produced sustained improvement. METHODS: Physiotherapists
      administered 1 to 2 months of TES to 39 children (20 minutes, 3 times a week).
      Fifteen continued to self-administer TES (30 minutes daily for more than 2
      months). Mean long-term follow-up of 30 of 39 patients was conducted using
      questionnaire review 3.5 years (range 1.9-4.7 years) later. Outcomes were
      evaluated by confidence intervals or paired t test. RESULTS: Seventy-three
      percent of patients perceived improvement, lasting more than 2 years in 33% and
      less than 6 months in 25% to 33%. Defecation frequency improved in 30%. Stools
      got wetter in 62% after stimulation and then drier again. Soiling improved in 75%
      and abdominal pain in 59%. Laxative use stopped in 52%, and 43% with
      appendicostomies stopped washouts. Soiling/Holschneider continence score improved
      in 81% (P = .0002). Timed sits switched to urge-initiated defecations in 80%
      patients. Eighty percent of relapsed patients elected to have home stimulation.
      CONCLUSION: TES holds promise for STC children. Improvement occurred in two
      thirds of children, lasting more than 2 years in one third, whereas symptoms
      recurred after 6 months in one third of children.

PMID- 22152872
TI  - Evaluation of defecative function 5 years or longer after laparoscopic-assisted
      pull-through for imperforate anus.
AB  - BACKGROUND: Laparoscopic anorectoplasty was introduced in 2000, but the procedure
      has not yet gained universal acceptance. Previous studies, including ours,
      reported satisfactory early postoperative outcome as compared with posterior
      sagittal anorectoplasty (PSARP), but mid- to long-term results are not available.
      Here, we aim to evaluate the mid- to long-term defecative function in these
      patients. MATERIALS AND METHODS: A retrospective study was carried out and
      included all patients who underwent laparoscopic-assisted anorectoplasty for high
      /intermediate-type imperforate anus between 2001 and 2005. Their degree of
      continence was graded according to the Krickenbeck classification and compared
      with historical controls treated with PSARP. The results were compared using
      chi(2) test, and P < .05 was considered statistically significant. RESULTS: There
      were 18 patients who underwent laparoscopic anorectoplasty (LAR) in the study
      period. They were compared with 20 historical PSARP patients. For defecation
      sensation, 16 of the 18 LAR patients were positive, whereas there were 16 of 20
      PSARP patients. Eight LAR patients were clean without any fecal soiling or
      incontinence (11/20 PSARP). Only 3 of 18 LAR had constipation as compared with 7
      of 20 PSARP. The need for rectal enema for evacuation was seen in 1 of 20 LAR
      patients and 2 of 20 PSARP patients (for all categories, P > .05). CONCLUSIONS:
      Mid- to long-term follow-up study revealed satisfactory defecative function for
      patients with high-/intermediate-type imperforate anus after LAR. The outcome is
      at least as good as PSARP. Longer term follow-up with larger sample size is
      necessary to demonstrate the benefits of LAR over PSARP.

PMID- 22152873
TI  - The transpubic approach for the correction of complex anorectal and urogenital
      malformations.
AB  - BACKGROUND: The transpubic approach has been used mainly to treat urethral
      injuries and prostate cancer. There are no reports describing this approach in
      anorectal malformations. METHODS: Forty-two patients who underwent a transpubic
      approach for their genitourinary/colorectal reconstruction were reviewed.
      Indications, complications, and follow-up were analyzed. A midline infraumbilical
      incision was used. The pubic cartilage was divided with needle cautery.
      Institutional review board approval was obtained (IRB# 2008-1317). RESULTS: The
      cases included complex malformations (16), covered exstrophy (15), long
      urogenital sinus with normal rectum (6), and reoperations in cloacas which had
      been left with persistent fistulae between vagina and urinary tract with normal
      rectum (5). Excellent exposure was achieved in all cases, allowing successful
      anatomical reconstruction. Functional results varied depending on the specific
      type of defect but were not expected to be good due to severe congenital or
      acquired anatomic defects. There were 3 complications related to the transpubic
      approach: pubic dehiscence, suspected osteomyelitis, and bleeding. CONCLUSION:
      The transpubic approach should be considered for the repair of complex anorectal
      and urogenital malformations, especially when adequate exposure cannot be
      achieved with an abdominal, perineal, or posterior sagittal approach. Another
      ideal indication is in patients with a normal rectum who were born with a complex
      urogenital sinus or underwent a failed attempted repair but were left with
      problems requiring reoperation in a scarred and fibrotic pelvis.

PMID- 22152874
TI  - Restoration of mechanically lengthened jejunum into intestinal continuity in
      rats.
AB  - PURPOSE: Prior studies demonstrated the feasibility of lengthening intestinal
      segments with mechanical force, but no previous studies have restored the
      lengthened segment back into intestinal continuity. METHODS: A 1-cm segment of
      isolated rat jejunum was lengthened using a Nitinol spring. After lengthening,
      this segment was restored into intestinal continuity via a transection of the
      intact small intestine. Rats were euthanized 2 weeks later to retrieve the
      restored intestinal segment for histologic and enzymatic analyses. RESULTS: The
      isolated jejunal segments were initially lengthened to 3.3 +/- 0.9 cm. After the
      lengthened segments were restored into intestinal continuity for 2 weeks, the
      final length of the restored segment was 1.9 +/- 0.7 cm. All rats continued to
      gain weight, and the intestine proximal to the restored jejunal segment remained
      normal 2 weeks later. The restored jejunal segment had an increase in crypt depth
      and no difference in villus height compared with normal jejunum. Sucrase activity
      in the restored segment was not different from that in normal jejunum.
      CONCLUSION: Mechanically lengthened jejunum can be restored into intestinal
      continuity and appears to have normal function. This further demonstrates the
      feasibility of mechanical enterogenesis as a potential therapy for short bowel
      syndrome.

PMID- 22152875
TI  - Primary anastomosis for meconium peritonitis: first choice of treatment.
AB  - PURPOSE: Newborn surgery for meconium peritonitis (MP) is sometimes very
      difficult owing to severe adhesions and bleeding. The aim of this study was to
      reveal the benefit of primary anastomosis (PA) for MP by comparing PA with
      multistep operations (MO). PATIENTS AND METHODS: We retrospectively reviewed 38
      patients with MP who underwent surgery in our institution from 1983 to 2009. From
      1983 to 2000, we essentially used MO. After 2001, we used PA with the exception
      of 1 patient. We performed MO on 20 patients (group A) and PA on 18 patients
      (group B). RESULTS: Mortality was 4 in 20 in group A and 1 in 18 in group B.
      Three patients in group A and 2 in group B required reoperation because of
      complications. After 2001, 14 of 16 patients underwent PA. Of the 2 patients for
      whom PA could not be performed, one was postresuscitation from cardiopulmonary
      arrest and the other was an extremely low-birth-weight infant. The only mortality
      among the patients who underwent PA occurred in a very low-birth-weight infant
      who died from intraoperative hepatic hemorrhage. CONCLUSION: PA can be performed
      for almost all patients with MP except for extremely low-birth-weight infants.

PMID- 22152876
TI  - Importance of evaluating for cow's milk allergy in pediatric surgical patients
      with functional bowel symptoms.
AB  - BACKGROUND: Cow's milk allergy (CMA) can cause functional bowel symptoms. This
      can lead to confusion and difficulty in managing pediatric surgical patients who
      also have CMA. We examined CMA's effect on the management of pediatric surgical
      patients in our institute. METHODS: With institutional review board approval, 14
      pediatric surgical patients with CMA were reviewed. Cow's milk allergy was
      diagnosed according to clinical findings and stimulation index (normal range
      <300%) of the lymphocyte stimulation test. RESULTS: The main symptoms were
      abdominal distension (n = 10), vomiting (n = 6), constipation (n = 2), and apnea
      (n = 1). Stimulation index median value was 731% (range, 341%-2132%). Patients
      were divided into 3 groups. In group 1 (n = 8), persistent postoperative bowel
      symptoms were initially considered related to surgical diseases. Following CMA
      diagnosis, CM elimination therapy improved symptoms. In group 2 (n = 4), CMA was
      diagnosed concurrently with surgical disease, and elimination therapy was
      continued postoperatively. In group 3 (n = 2), the pathogenesis of bowel symptoms
      was initially attributed to CMA and later diagnosed as Hirschsprung's disease.
      CONCLUSIONS: A high index of suspicion regarding the possibility of concurrent
      CMA may be necessary to manage bowel symptoms in pediatric surgical patients.

PMID- 22152877
TI  - The "all-in-one" appendectomy: quick, scarless, and less costly.
AB  - BACKGROUND: A technique for laparoscopic appendectomy (LAP APPY) that involves
      brief surgeon and operating room times, results in no appreciable scar, and
      requires few disposable supplies would be desirable. METHODS: During 2009, 508
      children underwent LAP APPY at our institution including 398 (78%) for acute, non
      perforated appendicitis. Our "all-in-one" operative procedure involves use of a
      single instrument through a side-arm viewing operative laparoscope which is
      inserted through a single, trans-umbilical port. Successful procedure completion
      rates and operative times ("cut-to-close") were determined. Our data for surgeon
      directed, disposable supply costs per procedure were collated by Child Health
      Corporation of America and compared with 2009 LAP APPY data (n = 5692) from 17
      other children's hospitals in the United States. RESULTS: We successfully
      completed 359 (90.2%) LAP APPY procedures using the all-in-one technique
      resulting in no appreciable scar. Additional ports were used in 9.8% and there
      were no conversions to open procedures. Median operative time for the all-in-one
      technique was 24 minutes (5-66 min). Our median surgeon-directed, disposable
      supply cost was the lowest in the study group and significantly less than the
      other 17 children's hospitals ($166 vs $748, P < .001). Median variation of
      supply costs among surgeons within each institution was $448 ($3-$870). Aggregate
      savings of nearly $1.3 million are predicted if all study surgeons were to reduce
      their disposable costs per procedure to the 25th percentile ($551). CONCLUSIONS:
      We conclude that the all-in-one laparoscopic appendectomy technique is quick,
      scarless, and less costly than conventional multi-port techniques. Wider
      application of the all-in-one technique seems indicated.

PMID- 22152878
TI  - Does age affect the outcomes and management of pediatric appendicitis?
AB  - PURPOSE: Although it is recognized that younger children have higher appendiceal
      perforation rates, little is known about the effect of age on postoperative
      morbidity. The purpose of this study was to determine whether age affects the
      outcome and management of pediatric appendicitis. METHODS: A retrospective review
      of all patients 14 years and younger who were treated for appendicitis over a 10
      year period was performed. Study outcomes included 30-day postoperative
      morbidity, use of laparoscopy, and length of hospitalization (LOH). Postoperative
      morbidity included rates of wound infection, postoperative abscess drainage, and
      readmission. Patients were categorized into 3 age groups: young (<=5 years),
      middle (6-9 years), and older (>=10 years). Data for univariate associations were
      analyzed using chi(2) and Wilcoxon rank sum tests and reported as medians with
      interquartile ranges (IQR). Study outcomes were also analyzed using multivariable
      regression. RESULTS: Overall, 5894 patients were identified. Median age was 10.3
      years (IQR 7.3-12.5), and 61% were boys. The perforation rate was highest for
      patients 5 years and younger (<=5 years, 51%; 6-9 years, 32%; >=10 years, 27%; P
      < .0001). Multivariable analysis demonstrated that although the need for
      postoperative abscess drainage was greatest in older children (10-14 years), the
      readmission rate and LOH was highest in the youngest children (<=5 years). Wound
      infection rates were similar across all age groups. CONCLUSIONS: Although older
      children had a higher risk of abscess drainage, younger children were more likely
      to have perforated appendicitis, be readmitted, and have longer LOH. Management
      of appendicitis differed according to age. Laparoscopic appendectomy was more
      frequently performed in older children, whereas the youngest children were more
      likely to be treated nonoperatively.

PMID- 22152879
TI  - Outcomes of perforated appendicitis in obese and nonobese children.
AB  - INTRODUCTION: Despite abundant data on the impact of obesity in adults, little
      data exist that examine the impact of obesity on surgical outcomes in children.
      Therefore, we analyzed the impact of obesity on children with perforated
      appendicitis. METHODS: We analyzed data from 3 prospective trials on perforated
      appendicitis between 2005 and 2009. Perforation was defined as a hole in the
      appendix or fecalith in the abdomen. There was no difference in abscess rate in
      the 6 arms of these trials. Body mass index (BMI) was calculated, and BMI
      percentile was identified according to sex and age. The obese group was defined
      as BMI greater than 95th percentile. Data were compared between nonobese and
      obese patients. RESULTS: There were 220 patients, of which 37 patients were
      obese. The obese group was older with no other differences in presentation. Mean
      length of stay was 7.9 days in the obese patients compared with 5.8 days for the
      nonobese (P < .001). Mean operative time was 55.2 minutes in obese patients
      compared with 43.6 for nonobese (P = .003). Abscess rate was 35% in obese
      patients compared with 15% for nonobese (P = .01). CONCLUSIONS: Obese children
      undergoing laparoscopic appendectomy for perforated appendicitis experience
      longer operative times and suffer worse outcomes.

PMID- 22152880
TI  - Transinguinal laparoscopic exploration for identification of contralateral
      inguinal hernias in pediatric patients.
AB  - BACKGROUND: The use of transinguinal laparoscopy for contralateral groin
      exploration during unilateral inguinal hernia repair has gained popularity.
      Controversy exists, however, regarding its use in older children. We report a
      large, single-surgeon series describing the safety and effectiveness of this
      procedure. METHODS: A retrospective review was completed of all cases of open
      inguinal hernia repair from 1997 to 2009 performed by the senior author. Patients
      were explored laparoscopically through the ipsilateral hernia sac to assess the
      contralateral groin. Exclusion criteria were an inadequate sac or preoperatively
      diagnosed bilateral inguinal hernia. RESULTS: A total of 649 children underwent
      open inguinal hernia repair. A preoperative diagnosis of bilateral hernia was
      made in 18% (n = 117), and of the 532 unilateral cases, an inadequate sac was
      present in 15% (n = 79). Transinguinal laparoscopic exploration was performed on
      the remaining 453 children. A hernia or contralateral patent processus vaginalis
      (CPPV) was found in 38% of children (n = 173). In children older than 8 years,
      32% demonstrated a hernia or CPPV on laparoscopic exploration. No complications
      occurred because of laparoscopy. CONCLUSION: Transinguinal laparoscopic
      exploration is safe and effective and should be routinely performed in pediatric
      patients of all ages because of the high prevalence of contralateral hernia and
      CPPV.

PMID- 22152881
TI  - Gubernaculum as icebreaker: do matrix metalloproteinases in rodent gubernaculum
      and inguinal fat pad permit testicular descent?
AB  - PURPOSE: Cryptorchidism is the most common male congenital abnormality. The
      rodent gubernaculum steers the testis from abdomen to scrotum postnatally by
      eversion and migration through the developing inguinal fat pad (IFP). We
      hypothesize that extracellular matrix remodeling in/around the gubernaculum is
      necessary for eversion and migration and is permitted by timed IFP maturation and
      aimed to examine regional development and matrix metalloproteinase (MMP) content.
      METHODS: Embryonic day 19 (E19) and postnatal days 0 and 2 (P0, P2) wild-type
      Sprague-Dawley rats (n = 10) were prepared for histologic examination (trichrome)
      and immunohistochemistry (membrane-type MMP-1 [MT1-MMP], MMP2) and analyzed using
      light/confocal microscopy. RESULTS: At E19, IFP contained fibroblasts and
      immature cells in an extensive collagenous extracellular matrix. Cells in the
      gubernaculum base were cytoplasmic-MT1-MMP-positive (inactive). At P0, the
      gubernaculum had everted, and adjacent cells were membranous-MT1-MMP-positive
      (active). At P2, the gubernaculum was migrating through the IFP, and adjacent
      cells were membranous-MT1-MMP-positive. Adipocyte maturation began cranially in
      the IFP and proceeded in a craniocaudal gradient until more uniformly mature at
      P2. CONCLUSION: The MT1-MMP-positive cells may remodel the gubernaculum for
      eversion and provide the collagenolysis necessary for migration, like an
      icebreaking ship, through the IFP, which matures to permit migration through
      collagen-rich tissue. Disruption of these processes may cause cryptorchidism.

PMID- 22152882
TI  - The effect of flutamide on expression of androgen and estrogen receptors in the
      gubernaculum and surrounding structures during testicular descent.
AB  - BACKGROUND/PURPOSE: Inguinoscrotal testicular descent is controlled by androgens
      between embryonic days E16-19, but androgen receptor (AR) and estrogen receptor
      (ER) locations are unknown. We aimed to find AR, ERalpha, and ERbeta in the
      gubernaculum and inguinal fat pad (IFP) in normal rats and after flutamide
      treatment. METHODS: Sprague-Dawley timed-mated rats were injected with flutamide
      (75 mg/kg body weight/5% ethanol + oil) on E16-19 or vehicle alone. Male fetuses
      or pups (5-10/group) were collected at E16; E19; and postnatal (P) days 0, 2, 4,
      8. Sections were prepared for hematoxylin and eosin or immunohistochemistry for
      AR, ERalpha, and ERbeta. Receptor labeling was quantitated as distinct nuclear
      labeling/100 MUm(2) in gubernaculum and IFP. RESULTS: There was minimal
      gubernacular AR-labeling until E19, dramatically increasing postnatally. By
      contrast, at E16-E19 there was significant IFP AR immunoreactivity suppressed by
      flutamide (P < .05). No ERalpha expression was observed, but ERbeta was expressed
      in both gubernaculum and IFP, maximally at E16, but unchanged by flutamide.
      CONCLUSIONS: During the androgen sensitivity window (E16-19), the gubernaculum
      contains ERbeta but minimal ERalpha or AR, while the IFP, which is supplied by
      the genitofemoral nerve, contains abundant AR that are flutamide-sensitive. These
      results suggest that the IFP could be the site of androgenic action controlling
      gubernacular development.

PMID- 22152883
TI  - Gone with the Wnt: the canonical Wnt signaling axis is present and androgen
      dependent in the rodent gubernaculum.
AB  - BACKGROUND/AIMS: How androgens control inguinoscrotal descent remains
      controversial but may include canonical Wnt signaling via the transcriptional co
      activator beta-catenin. The canonical Wnt pathway transcribes genes regulating
      mesenchymal cell migration, fate, extracellular matrix remodeling, and in
      addition Axin2, a feedback product that reliably identifies Wnt activation. The
      relationship between beta-catenin and androgen receptor warranted investigation
      into the involvement of the canonical Wnt pathway in testicular descent. METHODS:
      Gubernacula from male Sprague-Dawley control (n = 22) and flutamide-treated (n =
      18) rats at E17, E19, and D0 time-points were processed for immunohistochemistry.
      Sagittal sections stained for presence of androgen receptor, Axin2, and beta
      catenin were analyzed by fluorescent confocal microscopy. RESULTS: At E19, beta
      catenin was strongly expressed in the membrane of developing cremaster muscle
      cells and the cytoplasm of gubernacular core cells. Axin2 expression was
      ubiquitous in nuclei of gubernacular mesenchymal cells, representing canonical
      Wnt signaling. After androgen blockade, Axin2 was conspicuously absent in the
      fibroblasts of the gubernacular core while remaining unaffected elsewhere.
      Reduced staining of Axin2 in E17 and D0 gubernacula suggests that Wnt signaling
      coincides with androgen programming. CONCLUSION: Axin2 expression in the E19
      gubernaculum confirms canonical Wnt pathway activation. Its absence in the core
      of flutamide-treated gubernacula indicates Wnt down-regulation. As androgen is
      required for inguinoscrotal descent, downstream Wnt signaling may control initial
      gubernacular remodeling. Defects in this complex molecular process may play a
      role in cryptorchidism.

PMID- 22152884
TI  - Tubularized incised plate urethroplasty with dorsal inlay graft prevents
      meatal/neourethral stenosis: a single surgeon's experience.
AB  - BACKGROUND/PURPOSE: Snodgrass tubularized incised plate urethroplasty (SUP) is
      versatile and has good cosmesis. However, postoperative meatal/neourethral
      stenosis (M/N-S) is common enough for some surgeons to add a dorsal inlay graft
      (DIG) harvested from the inner prepuce and sutured to cover the longitudinal
      midline incision of the urethral plate. This is the first formal assessment of
      the effectiveness of DIG for preventing M/N-S. METHODS: We reviewed the medical
      records of 100 consecutive SUP cases performed by a single surgeon between 2003
      and 2010 comparing SUP + DIG (S + D group, n = 50) with SUP - DIG (S - D group, n
      = 50). Mean follow-up was 3.6 years. Data were analyzed statistically using the
      chi(2), 2-way ANOVA, and Mann-Whitney tests, with P < .05 considered significant.
      RESULTS: Severity of hypospadias and type of SUP were similar. Mean age at SUP
      was 3.3 years in S + D and 3.6 years in S-D (P = NS). There were 4 complications
      in the S + D group: urethrocutaneous fistula (n = 3) and neourethral stenosis
      without diverticulum (n = 1). There were 15 complications in the S-D group :
      meatal stenosis (n = 2), neourethral stenosis with or without diverticulum (n =
      6), urethrocutaneous fistula (n = 7) (P < .01). M/N-S was significantly less in
      the S + D group (1 vs 8; P < .05). CONCLUSIONS: We strongly recommend that DIG be
      performed routinely during SUP.

PMID- 22152886
TI  - Use of an omega-3 fatty acid-based emulsion in the treatment of parenteral
      nutrition-induced cholestasis in patients with microvillous inclusion disease.
AB  - Microvillous inclusion disease is a congenital intestinal epithelial cell
      disorder leading to lifelong intestinal failure. In this report, we discuss the
      use of a fish oil-based lipid emulsion in the treatment of 3 patients with
      microvillous inclusion disease who developed parenteral nutrition-associated
      liver disease.

PMID- 22152887
TI  - Synchronous ipsilateral Bochdalek and Morgagni diaphragmatic hernias: a case
      report.
AB  - The etiology of congenital diaphragmatic hernia (CDH) is unknown. Phenotypic
      patterns of CDH defects provide clues about normal diaphragm development and the
      pathophysiology of CDH. We report a case of a patient who was diagnosed with CDH
      postnatally and was found on imaging to have simultaneous Bochdalek and Morgagni
      hernias on the right side. During the operative repair of these defects, an
      additional left-sided Morgagni-type defect was also found. To the best of our
      knowledge, this form of CDH has not been previously reported.

PMID- 22152888
TI  - Pediatric clear cell sarcoma of the kidney with cavoatrial thrombus.
AB  - Clear cell sarcoma of the kidney (CCSK) is a rare renal tumor. Only 4 cases of
      CCSK with vascular thrombus have been reported, and 2 of these were pediatric
      cases. One of the children had an intraatrial thrombus as well. We describe a 3
      year-old boy who was diagnosed as having a Wilms tumor but did not respond to
      preresection chemotherapy. He underwent complete resection of the tumor under
      cardiopulmonary bypass. Histologic examination indicated that the tumor was a
      CCSK. The patient was then managed with appropriate chemotherapy and radiation
      therapy and is well 16 months after diagnosis.

PMID- 22152889
TI  - Trilogy of gastrointestinal atresias: a case report and review of the literature.
AB  - This is a case report of a child with a rare combination of pyloric and colonic
      atresias, imperforate anus, hypoganglionosis of the rectum and sigmoid colon,
      unilateral multicystic dysplastic kidney, bilateral sensorineural deafness,
      spondyloepimetaphyseal dysplasia, subglottic stenosis, growth failure, and limb
      anomalies.

PMID- 22152890
TI  - Survival in a 2-year-old boy with hemorrhage secondary to an aortoesophageal
      fistula.
AB  - Aortoesophageal fistula (AOF) in children with no history of cardiac disease or
      trauma is extremely rare, and survival is even rarer. We present a case of a 2
      year-old boy who presented with massive hematemesis secondary to a primary
      aortoesophageal fistula and was found at endoscopy to have a submucosal hematoma.
      He then suffered a cardiac arrest with further catastrophic bleeding only
      controlled by a Sengstaken-Blakemore tube. Subsequent cardiopulmonary bypass was
      instituted and allowed direct repair of the fistula. He was discharged home 4
      weeks later. The etiology of the fistula remains unknown.

PMID- 22152891
TI  - Paralysis of the rectus abdominis muscle after video-assisted thoracoscopic
      surgery for recurrent spontaneous pneumothorax.
AB  - Clinically apparent injury to an intercostal nerve associated with paralysis of
      the upper rectus abdominis is a rare complication of video-assisted thoracoscopic
      surgery (VATS), with no reports available in the pediatric literature. We present
      the case of a 16-year-old boy who underwent VATS blebectomy and pleurodesis
      followed by tube thoracostomy for recurrent spontaneous pneumothorax. Definitive
      reexpansion of the lung was achieved with no immediate complications, but the
      child complained of abnormal sensation and motor dysfunction of the left upper
      rectus at his first follow-up visit 2 weeks after the operation. Isolated
      muscular paralysis persisted at 2-month follow-up, although there was no
      associated activity limitation. Video-assisted thoracoscopic surgery is now a
      common practice and recognized as less morbid than open thoracotomy, but there
      exists scant literature regarding intercostal nerve injury and associated rectus
      abdominis paralysis. This report reviews the relevant published literature, with
      emphasis on the mechanism of nerve injury and avoidance of this complication.

PMID- 22152892
TI  - Surgery for hydrocele in children-an avoidable excess?
AB  - BACKGROUND: There is little consensus over the optimal timing of ligation of a
      patent processus vaginalis (PPV) in boys with hydrocele. We hypothesized that a
      proportion of procedures may be unnecessary because they are performed at an age
      before which the PPV may be expected to close spontaneously. Such excess may
      expose the child to unnecessary surgery and have significant cost implications.
      METHODS: A systematic literature review relating to timing of PPV ligation and a
      population-based study to define number of PPV ligations performed annually in
      England and age at surgery were conducted. RESULTS: Most hydroceles resolve
      before 2 years of age, but their natural history beyond this age is poorly
      documented. Current guidelines recommend PPV ligation at 2 years of age. An
      average of 2878 operations for hydrocele is performed per year in children in
      England. Commonest age at repair is 2 years. There are no randomized controlled
      trials comparing PPV ligation with an observational nonoperative approach.
      CONCLUSIONS: The natural history of hydrocele is poorly documented beyond the age
      of 2 years. There is no good evidence to support current practice. Delaying
      surgery may reduce the number of procedures necessary without increasing
      morbidity. A prospective study to investigate this is warranted.

PMID- 22152894
TI  - Mucosa-associated lymphatic tissue lymphoma of the lower lip in a child.
AB  - Mucosa-associated lymphatic tissue lymphoma of the lip in a child is a very rare
      clinical entity whose cause is poorly understood. We describe an 11-year-old boy
      who presented with a 5-month history of an asymptomatic nodule on the lower lip
      with the clinical appearance of a benign mucocele. After surgical excision of the
      lower lip lesion, lymphocyte phenotypic analysis and histologic examination of
      the specimen disclosed an extranodal marginal zone B-cell lymphoma of mucosa
      associated lymphatic tissue type of the buccal minor salivary glands. Mucosa
      associated lymphatic tissue lymphoma of the lip may clinically resemble a large
      mucocele. To prevent a delayed detection of lip mucosa-associated lymphatic
      tissue lymphoma, an incisional biopsy of large mucous cysts of the oral mucosa
      before marsupialization is recommended.

PMID- 22152893
TI  - Diagnostic imaging in cryptorchidism: utility, indications, and effectiveness.
AB  - BACKGROUND: Cryptorchidism (undescended testis) is the most common genitourinary
      anomaly in male infants. METHODS: We reviewed the available literature on the
      diagnostic performance of ultrasound, computed tomography, and magnetic resonance
      imaging (MRI) in localizing undescended testes. RESULTS: Ultrasound is the most
      heavily used imaging modality to evaluate undescended testes. Ultrasound has
      variable ability to detect palpable testes and has an estimated sensitivity and
      specificity of 45% and 78%, respectively, to accurately localize nonpalpable
      testes. Given the poor ability to localize nonpalpable testes, ultrasound has no
      role in the routine evaluation of boys with cryptorchidism. Magnetic resonance
      imaging has greater sensitivity and specificity but is expensive, not universally
      available, and often requires sedation for effective studies of pediatric
      patients. Diagnostic laparoscopy has nearly 100% sensitivity and specificity for
      localizing nonpalpable testes and allows for concurrent surgical correction.
      CONCLUSIONS: Although diagnostic imaging does not have a role in the routine
      evaluation of boys with cryptorchidism, there are clinical scenarios in which
      imaging is necessary. Children with ambiguous genitalia or hypospadias and
      undescended testes should have ultrasound evaluation to detect the presence of
      mullerian structures.

PMID- 22152895
TI  - Transumbilical endoscopic surgery for completely enclosing inguinal hernias in
      children.
AB  - BACKGROUND/PURPOSE: There has been great interest in natural orifice transluminal
      endoscopic surgery in recent years. We report another new approach for pediatric
      inguinal hernia repair: transumbilical endoscopic surgery (TUES). Compared with
      the natural orifice transluminal endoscopic surgery technique, TUES can obtain
      similar scarless results on the abdomen. METHODS: In our hospital, 2-trocar TUES
      was the standard procedure used to repair pediatric inguinal hernias. Through 2
      intraumbilical incisions, two 5-mm trocars were inserted into the abdomen under
      laparoscopic guidance. With the use of a needle-holding forceps, a round needle
      with 2-0 nonabsorbable suture material was introduced into the peritoneal cavity
      through the anterior abdominal wall near the internal inguinal ring. The orifice
      of the hernial sac was closed extraperitoneally with a purse-string suture around
      the internal inguinal ring, and intraperitoneal knot-tying was performed.
      RESULTS: A total of 76 inguinal repairs were performed in 64 children (age range,
      6 months to 9 years; median, 3.8 years; 44 boys, 20 girls). All operations were
      completed successfully by TUES, with the exception of one case of intraoperative
      bleeding because the inferior epigastric vein was punctured. The mean operating
      time was 20 minutes (range, 15-30 minutes). No postoperative bleeding, hydrocele,
      or scrotal edema in this group of patients was found, and there were no known
      cases of postoperative testicular atrophy or hypotrophy nor hernia recurrence on
      the symptomatic side. CONCLUSIONS: Our preliminary experience shows satisfactory
      outcomes with TUES for completely enclosing inguinal hernias in children. This
      technique appears to be safe, effective, and reliable. The cosmetic result is
      excellent.

PMID- 22152896
TI  - Single-site incision laparoscopic cholecystectomy in children: a single-center
      initial experience.
AB  - Laparoscopic cholecystectomy is the standard approach in most pediatric surgical
      centers. In an attempt to further minimize the surgical trauma and improve
      cosmetic outcome, new techniques with a single incision through the umbilicus
      have been proposed. There are still few reports concerning this technique in the
      pediatric population. We evaluated the feasibility of the single incision for
      laparoscopic cholecystectomy in children. We performed the operation in 10
      patients, with a mean age of 12 years, mean operating time of 122 minutes, and
      mean hospital stay of 2 days. No complications occurred, and no conversion to
      open surgery was needed. In 1 patient, an extra 5-mm port was necessary. The
      cosmetic results were very satisfactory. In our experience, despite its technical
      difficulty and initial learning curve, single-incision laparoscopic
      cholecystectomy in the pediatric population is a safe and feasible method.

PMID- 22152897
TI  - The bronchial blocker: why will it not come out?

PMID- 22152898
TI  - Teratoid Wilms' tumor: case report of a rare variant that can mimic aggressive
      biology during chemotherapy.
AB  - Teratoid Wilms' tumor is considered by some as a variant of Wilms' tumor
      containing at least 50% heterologous differentiated tissue. Fewer than 30 cases
      have been described. We report a 9-month-old boy with bilateral Wilms' tumors who
      did not respond to multiagent chemotherapy and underwent right nephrectomy that
      showed a teratoid Wilms' tumor. The patient continued to survive despite
      cessation of treatment. The overall predominance of differentiated stromal
      elements in this subtype of Wilms' tumor might explain the poor response to
      chemotherapy yet generally favorable outcome. Recognition of this subtype on
      biopsy might justify earlier surgical intervention that, for bilateral tumors,
      might allow for greater nephron sparing.

PMID- 22152899
TI  - Bi-caval dual lumen venovenous extracorporeal membrane oxygenation and high
      frequency percussive ventilatory support for postintubation tracheal injury and
      acute respiratory distress syndrome.
AB  - Bi-caval dual lumen venovenous extracorporeal membrane oxygenation (VV-ECMO) as a
      nonoperative approach to postintubation tracheal injury has not been described.
      We report the case of a 7-year-old boy who sustained a postintubation tracheal
      injury, developed acute respiratory distress syndrome from aspiration and viral
      pneumonitis, and was supported on bi-caval dual lumen VV-ECMO for 16 days until
      the trachea healed without surgical repair. Before ECMO decannulation, high
      frequency percussive ventilation using a volumetric diffusive respiration
      ventilator was used for lung recruitment and airway clearance without disruption
      of the healed trachea. The use of ECMO to allow for lower mean airway pressure
      during initial healing and high-frequency percussive ventilation for lung
      recruitment and secretion clearance is a promising strategy to allow nonoperative
      tracheal injury repair in critically ill patients with multiple comorbidities.

PMID- 22152900
TI  - Complete urogenital nonunion.
AB  - A 7.5-year-old boy was admitted to our department with left undescended testis.
      On surgical exploration, the vas deferens and epididymis were normal in
      appearance in its route to the scrotum, but no obvious testis or testis-like
      structure was identified. Exploration was extended to the abdominal cavity via
      the processus vaginalis, and the testis was found near the sigmoid colon without
      any connection to the vas deferens and epididymis. The testis was freed from
      surrounding structures preserving the testicular vasculature, and an orchidopexy
      was performed. In cases of nonpalpable testis with the vas deferens and
      epididymis reaching to the scrotum, an intra-abdominal testis owing to a nonunion
      phenomenon must be considered, and extended exploration should be performed.

PMID- 22152901
TI  - Pediatric synchronous bilateral ovarian torsion: a case report and review of the
      literature.
AB  - Ovarian torsion is a surgical emergency that can present with a variety of
      symptoms and hence is difficult to diagnose. We present the first case of a
      pediatric synchronous bilateral ovarian torsion in ovaries without pathology and
      review its presentation, diagnosis, treatment, outcome, and the associated
      literature.

PMID- 22152902
TI  - Colon atresia and frontal encephalocele: a rare association.
AB  - The association of colonic atresia with craniofacial anomalies has been well
      described and probably represents a malformative event that occurs in the early
      embryonal period. We present a case of an infant with colonic atresia and a
      frontal encephalocele and believe this to be a newly reported association. We
      review possible pathogenic mechanisms.

PMID- 22152903
TI  - Superior mesenteric artery syndrome: a rare cause of complete intestinal
      obstruction in neonates.
AB  - Superior mesenteric artery syndrome (SMAS) is an uncommon cause of high
      intestinal obstruction in neonates; it is owing to incomplete obstruction in the
      third part of the duodenum caused by compression between the SMA and abdominal
      aorta. In neonates, complete intestinal obstruction owing to SMAS has been very
      rarely reported in the literature .We present a 7-day-old previously healthy male
      infant with a short history of gastroenteritis and sepsis followed by progressive
      abdominal distension and persistent bilious vomiting that resulted in hypovolemic
      shock. The patient was aggressively resuscitated, and a gastrografin study showed
      a hugely distended stomach with an abrupt narrowing at the third part of the
      duodenum. Exploratory laparotomy unexpectedly revealed a high insertion of the
      duodenum at the ligament of Treitz, with upward displacement and SMA compression
      leading to duodenal obstruction. The ligament of Treitz was divided, and the
      duodenum, mobilized. The postoperative course was uneventful. Although extremely
      rare, SMAS should be considered as one of the differential diagnoses in newborns
      presenting with complete intestinal obstruction, especially if preceded by
      gastroenteritis or sepsis-like symptoms.

PMID- 22152904
TI  - Sigmoid perforation and bucket-handle tear of the mesocolon after bicycle
      handlebar injury: a case report and review of the literature.
AB  - We describe an unusual case of sigmoid colon perforation secondary to a bicycle
      handlebar injury. Because the patient presented 2 days after the initial injury,
      we suspected that the colon perforation was not the immediate result of the
      bicycle accident but, rather, was secondary to devascularization. At operation,
      we found a bucket-handle tear of the colonic mesentery, which was the patient's
      primary injury and cause of the perforated colon.

PMID- 22152905
TI  - Percutaneous management of bile-plug syndrome: a case report.
AB  - Bile-plug syndrome is defined as an obstruction of the common bile duct by bile
      sludge in full-term infants. It is a correctable cause of obstructive jaundice in
      infants and is generally treated surgically. Here, we present a case of a 5-month
      old infant with bile-plug syndrome, which was treated by percutaneous biliary
      interventions. To the best of our knowledge, percutaneous treatment of bile-plug
      syndrome is reported for the first time in an infant. This minimal invasive
      treatment modality may be a useful alternative to surgery in infants with bile
      plug syndrome.

PMID- 22152906
TI  - Metanephric stromal tumor: a challenging diagnostic entity in children.
AB  - A case with a renal mass diagnosed as metanephric stromal tumor is presented. A 6
      year-old boy presented with frequently recurring urinary tract infections. He had
      been followed up at different medical centers for the last 2 years with a 2 * 2
      cm simple cyst localized in the inferior pole of the left kidney. At our center,
      ultrasonography revealed a heterogeneous mass in the left kidney with a central
      cystic component. The patient underwent operation for left renal mass, and
      heminephrectomy was performed. The 5 * 4 * 2.5 cm left heminephrectomy specimen
      showed a partially cystic mass composed of bland spindle cells distributed
      haphazardly, entrapping tubules and glomeruli and producing fine collarettes
      around some tubules. The cysts were lined with a 1-layered flat or cuboidal
      epithelium. Histopathologically, the tumor was diagnosed as metanephric stromal
      tumor. Metanephric stromal tumor is a rare renal neoplasm of childhood that can
      present as a cystic mass, and the solid component can go radiologically
      undetected because of the blurring infiltrative margins. By presenting this rare
      entity, the authors suggest that this should be included in the differential
      diagnosis, thereby helping to avoid complications and unnecessary treatment.

PMID- 22152907
TI  - [Pathologic substrate of synucleinopathies. Introduction].

PMID- 22152908
TI  - [Role of genetics in the etiology of synucleinopathies].
AB  - The protein family known as synucleins is composed of alpha-, beta- and gamma
      synuclein. The most widely studied is the alpha-synuclein protein due to its
      participation in essential processes of the central nervous system. Neurotoxicity
      of this protein is related to the presence of multiplications (duplications and
      triplications) and point mutations in the gene sequence of the alpha-synuclein
      gene (SNCA), differential expression of its isoforms and variations in post
      transductional modifications. Neurotoxicity is also related to cytoplasmic
      inclusions known as Lewy bodies (LBs) and Lewy neurites (LNs), which are also
      present in alpha-synucleinopathies. In general, the beta-synuclein protein,
      codified by the SNCB gene, acts as a regulator of processes triggered by alpha
      synuclein and its function is altered by variations in the gene sequence, while
      gamma-synuclein, codified by the SNCG gene, seems to play a major role in certain
      tumoral processes.

PMID- 22152909
TI  - [Neuropsychological characteristics and diagnostic approach to Parkinsons disease
      dementia and Lewy body dementia].
AB  - When approaching the neurophysiological characteristics and diagnostic approach
      to Parkinson's disease dementia (PDD) and Lewy body dementia (LBD), the first
      idea that comes to mind is that both types of dementia fall within the group of
      subcortical dementias, with the practical implications that this observation
      entails. We should therefore leave our knowledge of Alzheimer's dementia and
      other cortical dementias to one side as, in most cases, these forms of dementia
      do not correspond clinically or diagnostically to subcortical dementias.
      Therefore, the clinical and therapeutic approach of PDD and LBD differs from that
      of cortical dementias in form, if not in essence.

PMID- 22152910
TI  - [Symptoms of Lewy body dementia and clinical course compared with Alzheimer's
      disease].
AB  - Lewy body dementia (LBD) is a neurodegenerative disease with well-defined
      symptoms and established clinical criteria, characterized by the presence of
      cortical and subcortical dementia, accompanied by some characteristic features
      such as Parkinsonism, visual hallucinations and fluctuations in alertness and
      attention, as well as hypersensitivity to neuroleptics. Compared with Alzheimer's
      disease, LBD seems to have a more rapid clinical course and greater mortality.
      The differences with Alzheimer's disease may be more apparent in the initial
      stages of the disease but tend to disappear with disease progression. Because of
      the greater presence of neuropsychiatric symptoms and the higher degree of
      dependency in LBD, there is greater caregiver overload and probably greater
      resource use.

PMID- 22152911
TI  - [Treatment of Lewy body dementia].
AB  - Lewy body dementia (LBD) is more frequent than previously considered and is
      characterized by the scarcity of therapeutic resources and the difficulty of
      treatment since many patients are hypersensitive to neuroleptics. Although
      further research is required in this field, standardization of the diagnostic
      criteria has improved the data obtained from research. Currently,
      anticholinesterase drugs have proven utility in LBD and there is increasing
      evidence that memantine can also be useful. Typical neuroleptics are dangerous in
      these patients and should never be used. Among atypical neuroleptics, quetiapine
      is the best option, although conclusive data are lacking.

PMID- 22152912
TI  - [Introduction. Alzheimer's disease before dementia].

PMID- 22152913
TI  - [The diagnostic approach to early Alzheimer's disease. What are we talking about?
      Conceptual considerations].
AB  - Progress in knowledge of the physiopathology of Alzheimer's disease over the last
      few decades has allowed much earlier diagnosis, even before the onset of clinical
      symptoms. Although the use of biomarkers is still far from being widespread and
      cannot be recommended outside research settings, their potential use has led to a
      review of the diagnostic criteria employed in the last few years. Among other
      criteria, asymptomatic and prodromal phases have been definitively incorporated
      into the spectrum of the disease and have been redefined. In future, the
      possibility of an earlier and more accurate diagnosis will allow the application
      of treatments acting in these phases, delaying progression to more advanced
      stages or even halting the disease before clinical manifestations develop.
      Currently, such treatments are still far from being a reality and interest in
      biomarkers centers on research since their detection could allow standardization
      of the samples used in clinical trials and exclusion of individuals showing signs
      of prodromal disease but who will never develop the disease.

PMID- 22152914
TI  - [Role of biomarkers in the early diagnosis of Alzheimer's disease].
AB  - Alheimer's disease is the most frequent cause of cognitive decline and behavioral
      abnormalities in adults. Diagnosis is currently made in the advanced phases. An
      an early diagnosis in the prodromal phase (or earlier if possible) is required
      for the prevention of this disease, its early management and the development of
      potential therapies that could alter its natural course. The syndromic concept of
      mild cognitive impairment (the presence of detectable and quantifiable
      deterioration in one of the cognitive domains but without affecting -or without
      substantially affecting- autonomic performance of instrumental function) and its
      variants has aided understanding of the predementia stages of Alheimer's disease,
      even though its etiology may involve multiple factors. The use of biomarkers such
      as determination of the proteins involved in the disease in cerebrospinal fluid
      (Abeta42-amyloid, total and phosphorylated tau) and measurement of the
      hippocampus and entorhinal cortex with magnetic resonance imaging and positron
      emission tomography (both glucose and amyloid measurements), alone or combined,
      could allow early and etiologic diagnosis. Patients with Alzheimer's disease show
      reduced Abeta42-amyloid levels and increased total and phosphorylated tau levels
      in cerebrospinal fluid.

PMID- 22152915
TI  - [Neuropsychology and early diagnosis].
AB  - The presence of histopathological lesions characteristic of Alzheimer's disease,
      senile plaques and neurofibrillar degeneration in the brains of cognitively
      normal individuals has been well documented in several longitudinal
      clinicopathological studies over the last two decades. Clinical and pathological
      epidemiological data suggest that Alzheimer's disease can begin to develop almost
      a decade before the first clinical manifestations appear. The present article
      reviews the studies investigating cognitive alterations before the disease
      manifests. All these studies reveal the presence of alterations in preclinical
      phases in cognitive functions other than memory, such as those related to
      attention, processing speed and verbal fluency. Assessment of memory with tools
      sensitive to hippocampal memory impairment is recommended. The best predictor is
      having each individual's baseline performance, which can then be used for
      comparison with subsequent performance. Once reduced performance is detected
      (even when within the "normal" range), affected persons should be referred to
      specific units able to diagnose the disease in the early stages.

PMID- 22152916
TI  - [Predementia Alzheimer's disease. Benefits of early diagnosis].
AB  - Given population aging and the rise in the number of persons with Alzheimer's
      disease, measures that aim not only to delay but also to prevent the development
      of this disease are increasingly required. Advances in the diagnosis of
      Alzheimer's disease support the need for a review of current clinical standards
      for mild cognitive impairment and provide new goals in the early treatment of
      this disease. The current diagnostic process should be refocussed toward the
      pathological substrate of this disease rather than symptoms in order to initiate
      therapeutic measures as soon as possible without waiting for clinical
      manifestations to appear. Such an approach is essential in patients with greater
      cognitive reserve, in whom the lesions are usually more severe at diagnosis and
      treatment is less effective. To identify disease-modifying therapies to delay the
      onset of the clinical symptoms of Alzheimer's disease in cognitively intact
      persons at high risk, biomarkers for this disease must be validated. A single
      biomarker is unlikely to provide the required diagnostic accuracy and therefore a
      multimodal approach, incorporating biochemical, neuropathological and anatomical
      and metabolic neuroimaging methods, should be employed. To optimize the results
      of drugs under investigation, a combination of biomarkers should be used to
      select appropriate participants in the earliest phases of the disease, and
      disease progression should be followed-up. Early diagnosis might clarify
      essential questions in the care of patients with Alzheimer's disease, such as the
      possibility of distinguishing among various subtypes, thus encouraging the
      development of optimal treatments for each. The ultimate goal is to develop
      disease-modifying treatments that could be initiated early, while patients are
      asymptomatic or only minimally symptomatic, to maintain their quality of life.

PMID- 22152917
TI  - [Ethical considerations in the presymptomatic diagnosis of Alzheimer's disease].
AB  - Research into the human genome has undoubtedly opened up a new perspective in
      medicine. The ability to identify the cause of specific diseases, especially
      neurodegenerative diseases, will definitively change the concepts of disease and
      treatment, while advances such as antibiotic therapy and anesthesia will be
      relegated to history. However, the arrival of genome medicine poses major
      bioethical challenges, many of which remain to be resolved. We review the
      applicability, results and consequences of predictions based on genetic tests for
      presymptomatic Alzheimer's disease, as well as the dilemmas and contradictions
      that are already arising as a result of the commercialization of predictive tests
      for public use with little or no medical supervision. Given that there is
      currently no effective treatment of Alzheimers disease, the greatest challenge
      and contradiction lies in managing the results of predictive tests. There are no
      indications for the performance of predictive genetic tests in late or sporadic
      Alzheimer's disease or for counselling of persons requesting these tests. The
      PICOGEN program provides a safe, effective, reliable and satisfactory option for
      persons requesting these tests who meet the inclusion criteria. Currently,
      caution should be the norm when considering the performance of predictive tests
      in presymptomatic dementia.

PMID- 22152918
TI  - A gestational low-protein diet represses p21(WAF1/Cip1) expression in the mammary
      gland of offspring rats through promoter histone modifications.
AB  - Maternal exposure to environmental agents throughout pregnancy may change certain
      metabolic processes during the offspring's mammary gland development and alter
      the epigenome. This may predispose the offspring to breast cancer later in life.
      The purpose of the present study was to examine the effect of maternal protein
      restriction on the regulation of cyclin-dependent kinase inhibitor 1 (p21) gene
      expression in the mammary gland of rat offspring. Timed-mated Sprague-Dawley rats
      were fed one of the two isoenergetic diets, control (C, 18 % casein) or low
      protein (LP, 9 % casein), during gestation. Compared with the C group, LP
      offspring showed a decrease of p21 in the mammary gland at both the mRNA and
      protein levels. Chromatin immunoprecipitation assay demonstrated that the down
      regulation of p21 transcription in LP offspring was associated with reduced
      acetylation of histone H3 and dimethylation of H3K4 within the p21 promoter
      region, but was not associated with acetylation of histone H4 or histone
      methylation. DNA methylation analysis using bisulphite sequencing did not detect
      differences in methylation at the p21 promoter between the offspring of the C and
      LP groups. We conclude that maternal protein restriction inhibits p21 gene
      expression in the mammary gland of offspring through histone modifications at the
      promoter region of the p21 gene.

PMID- 22152919
TI  - A membrane-free, continuously feeding, single chamber up-flow biocatalyzed
      electrolysis reactor for nitrobenzene reduction.
AB  - A new bioelectrochemical system (BES), a membrane-free, continuous feeding up
      flow biocatalyzed electrolysis reactor (UBER) was developed to reduce oxidative
      toxic chemicals to less- or non-toxic reduced form in cathode zone with oxidation
      of electron donor in anode zone. Influent was fed from the bottom of UBER and
      passed through cathode zone and then anode zone. External power source (0.5 V)
      was provided between anode and cathode to enhance electrochemical reactions.
      Granular graphite and carbon brush were used as cathode and anode, respectively.
      This system was tested for the reduction of nitrobenzene (NB) using acetate as
      electron donor and carbon source. The influent contained NB (50-200 mg L(-1)) and
      acetate (1000 mg L(-1)). NB was removed by up to 98% mainly in cathode zone. The
      anode potential maintained under -480 mV. The maximum NB removal rate was up to
      3.5 mol m(-3) TV d(-1) (TV=total empty volume) and the maximum aniline (AN)
      formation rate was 3.06 mol m(-3) TV d(-1). Additional energy required was less
      than 0.075 kWh mol(-1)NB. The molar ratio of NB removed vs acetate consumed
      varied from 4.3 +/- 0.4 to 2.3 +/- 0.1 mol mol(-1). Higher influent phosphate or
      acetate concentration helped NB removal rate. NB could be efficiently reduced to
      AN as the power supplied of 0.3 V.

PMID- 22152920
TI  - Irradiation effect on leaching behavior and form of heavy metals in fly ash of
      municipal solid waste incinerator.
AB  - Fly ash from a municipal solid waste incinerator (MSWI) is commonly classified as
      hazardous waste. High-energy electron beam irradiation systems have gained
      popularity recently as a clean and promising technology to remove environmental
      pollutants. Irradiation effects on leaching behavior and form of heavy metals in
      MSWI fly ash have not been investigated in any significant detail. An electron
      beam accelerator was used in this research. Electron beam irradiation on fly ash
      significantly increased the leaching potential of heavy metals from fly ash. The
      amount of absorbed dose and the metal species affected leaching behavior. When
      electron beam irradiation intensity increased gradually up to 210 kGy,
      concentration of Pb and Zn in the leachate increased linearly as absorbed dose
      increased, while that of Cu underwent no significant change. Concentration of Pb
      and Zn in the leachate increased up to 15.5% (10.7 mg/kg), and 35.6% (9.6 mg/kg)
      respectively. However, only 4.8% (0.3mg/kg) increase was observed in the case of
      Cu. The results imply that irradiation has significant effect on the leaching
      behavior of heavy metals in fly ash, and the effect is quite different among the
      metal species tested in this study. A commonly used sequential extraction
      analysis which can classify a metal species into five forms was conducted to
      examine any change in metal form in the irradiated fly ash. Notable change in
      metal form in fly ash was observed when fly ash was irradiated. Change in Pb form
      was much greater than that of Cu form. Change in metal form was related to
      leaching potential of the metals. Concentration of heavy metal in leachate was
      positively related to the exchangeable form which is the most mobile. It may be
      feasible to treat fly ash by electron beam irradiation for selective recovery of
      valuable metals or for pretreatment prior to conventional processes.

PMID- 22152921
TI  - DFT investigation of Ni(II) adsorption onto MA-DTPA/PVDF chelating membrane in
      the presence of coexistent cations and organic acids.
AB  - Melamine-diethylenetriaminepentaacetic acid/polyvinylidene fluoride (MA
      DTPA/PVDF) chelating membrane bearing polyaminecarboxylate groups was used to
      remove Ni(II) from nickel plating effluents. Adsorption experiments were
      conducted to study the adsorption of the membrane towards Ni(II) in Ni(II)
      Ca(II), Ni(II)-NH(4)(+), Ni(II)-Fe(III) binary systems, and Ni(II)-lactic acid,
      Ni(II)-succinic acid and Ni(II)-citric acid complex systems. For the ternary
      nickel plating processes, the effects of 3d transition metals including Fe(II),
      Co(II), Cu(II) and Zn(II) on Ni(II) adsorption were evaluated. The influences of
      the aforementioned coexistent cations and organic acids were elucidated by the
      continuum solvation model (COSMO)-corrected density functional theory (DFT)
      method. Geometries and complexation energies were analyzed for metal-MA-DTPA and
      Ni(II)-organic acid complexes. DFT results accord with the experimental data,
      indicating that DFT is helpful to evaluate the complexation between the membrane
      and metal cations. The coexistent Ca(II) tends to form more stable complex with
      MA-DTPA ligand than NH(4)(+) and Fe(III), and can interfere with the formation of
      Ni(II)-MA-DTPA complex. The complexing sequence of 3d metals with MA-DTPA ligand
      is Zn(II)<Co(II)<Ni(II)<Fe(II)<Cu(II). Therefore, both Fe(II) and Cu(II) have the
      considerable competition with Ni(II). The stabilities of Ni(II)-organic acid
      complexes follow the order of lactic acid<succinic acid<citric acid, but cannot
      be comparable to that of Ni(II)-MA-DTPA complex.

PMID- 22152922
TI  - An overview of biodiesel soil pollution: data based on cytotoxicity and
      genotoxicity assessments.
AB  - Biodiesel production has received considerable attention in the recent past as a
      nonpolluting fuel. However, this assertion has been based on its biodegradability
      and reduction in exhaust emissions. Assessments of water and soil biodiesel
      pollution are still limited. Spill simulation with biodiesel and their diesel
      blends in soils were carried out, aiming at analyzing their cytotoxic and
      genotoxic potentials. While the cytotoxicity observed may be related to diesel
      contaminants, the genotoxic and mutagenic effects can be ascribed to biodiesel
      pollutants. Thus, taking into account that our data stressed harmful effects on
      organisms exposed to biodiesel-polluted soils, the designation of this biofuel as
      an environmental-friendly fuel should be carefully reviewed to assure
      environmental quality.

PMID- 22152923
TI  - Intimal aortic sarcoma mimicking ruptured thoracoabdominal type IV aneurysm. A
      rare case report and review of the literature.
AB  - Primary intimal aortic sarcoma represents a very rare and highly lethal medical
      entity. Diagnosis is made either by embolic events caused by the tumor or by
      surrounding tissue symptoms such as pain. Herein we report an extremely rare case
      of a 51-year-old man previously operated for ascending aortic aneurysm, who
      presented with clinical and radiological findings suggestive of a ruptured
      thoracoabdominal type IV aneurysm. The patient underwent radical resection of the
      aorta and surrounding tissue with placement of a composite 4-branched graft. The
      diagnosis was made by frozen section and regular histopathologic examination of
      the specimen and the patient received adjuvant chemotherapy. Nine months after
      surgery the patient is still alive and has no signs of recurrence. We review the
      literature and discuss the option of postoperative chemotherapy.

PMID- 22152924
TI  - [Indicators in primary care: reality or desire. SESPAS report 2012].
AB  - The aim of this article is two-fold: firstly, to illustrate international
      experiences of assessing primary care performance by using examples of both cross
      country comparisons and national assessment efforts and, secondly, to describe
      the progress achieved to date in the articulation of the Spanish Primary Care
      Information System. The central role assigned to primary care in conceptual
      frameworks clashes with the severe limitations in the quality and availability of
      the data required to construct the indicators. The lack of systematic and
      standardized databases covering diagnosis, procedures and intermediate results in
      individual patients is endemic across countries. Filling this gap has become a
      priority in most countries, especially during the last decade. In Spain, the
      concept of the Primary Care Information System appeared in 2003 and the first
      data/results were published in 2006. Since then, distinct elements have been
      progressively incorporated with the involvement of the various autonomous regions
      in Spain. Currently, the system includes various aspects such as the population
      assigned, the available resources, a national catalogue of primary care centers,
      and activity. The next challenge in this work in progress is to build a database
      of clinical information.

PMID- 22152925
TI  - [Systematic review of studies assessing the cost of adverse drug reactions].
AB  - OBJECTIVE: Adverse drug reactions (ADRs) are an important healthcare problem. The
      objective of this study was to review published articles analyzing the cost of
      ADRs in any healthcare setting. METHOD: We conducted a search of articles
      published on the cost of ADRs in the bibliographic databases from 1970 to 2010.
      We identified 28 studies and selected 16 that included cases of ADR fitting the
      World Health Organization's definition of these events. The information on the
      characteristics of the study design, the types of costs analyzed and the reported
      results were reviewed. RESULTS: The design features and populations included in
      the studies were heterogeneous. Only two studies explicitly defined the
      perspective adopted. Only five studies compared cases of ADR with matched
      controls without ADRs. All studies analyzed direct healthcare costs, but none
      analyzed indirect or intangible costs. Fourteen publications analyzed the costs
      of length of hospital stay. The average (SD) percentage of ADRs was 3.04% (0.2)
      [median 2.4%, range 0.7% to 26.1%]. The median length of hospital stay in
      patients with ADRs was 8.8 days (range: 0.15 to 19.2 days). Accounting systems
      and monetary costs varied widely. CONCLUSION: Studies on the costs of ADRs are
      highly heterogeneous and have evaluated direct healthcare costs in hospitals.
      Their results indicate that ADRs generate substantial costs. More studies using
      appropriate methodology are needed on the costs of ADRs.

PMID- 22152926
TI  - Accuracy and reliability of self-reported weight and height in the Sister Study.
AB  - OBJECTIVE: To assess the accuracy and reliability of self-reported weight and
      height and identify the factors associated with reporting accuracy. DESIGN:
      Analysis of self-reported and measured weight and height from participants in the
      Sister Study (2003-2009), a nationwide cohort of 50 884 women aged 35-74 years in
      the USA with a sister with breast cancer. SETTING: Weight and height were
      reported via computer-assisted telephone interview (CATI) and self-administered
      questionnaires, and measured by examiners. SUBJECTS: Early enrolees in the Sister
      Study. There were 18 639 women available for the accuracy analyses and 13 316 for
      the reliability analyses. RESULTS: Using weighted kappa statistics, comparisons
      were made between CATI responses and examiner measures to assess accuracy and
      CATI and questionnaire responses to assess reliability. Polytomous logistic
      regression evaluated factors associated with over- or under-reporting. Compared
      with measured values, agreement was 96 % for reported height (+/-1 inch (+/-2.5
      cm); weighted kappa = 0.84) and 67 % for weight (+/-3 lb (+/-1.36 kg); weighted
      kappa = 0.92). Obese women (BMI >= 30 kg/m2) were more likely than normal-weight
      women to under-report weight by >=5 % and underweight women (BMI < 18.5 kg/m2)
      were more likely to over-report. Among normal-weight and overweight women (18.5
      kg/m2 <= BMI < 30 kg/m2), weight cycling and lifetime weight difference >=50 lb
      (>=22.68 kg) were associated with over-reporting. CONCLUSIONS: US women in the
      Sister Study were reasonably reliable and accurate in reporting weight and
      height. Women with normal-range BMI reported most accurately. Overweight and
      obese women and those with weight fluctuations were less accurate, but even among
      obese women, few under-reported their weight by >10 %.

PMID- 22152927
TI  - C(1) metabolism and CVD outcomes in older adults.
AB  - CVD is the most common cause of death in people over 65 years. This review
      considers the latest evidence for a potential protective effect of C(1) donors
      (folate and the metabolically related B-vitamins) in CVD. Such an effect may or
      may not be mediated via the role of these nutrients in maintaining plasma
      homocysteine concentrations within a desirable range. Despite predictions from
      epidemiological studies that lowering plasma homocysteine would reduce
      cardiovascular risk, several secondary prevention trials in at-risk patients
      published since 2004 have failed to demonstrate a benefit of homocysteine
      lowering therapy with B-vitamins on CVD events generally. All these trials were
      performed in CVD patients with advanced disease; thus current evidence suggests
      that intervention with high-dose folic acid is of no benefit in preventing
      another event, at least in the case of heart disease. The evidence at this time,
      however, is stronger for stroke, with meta-analyses of randomised trials showing
      that folic acid reduces the risk of stroke, particularly in people with no
      history of stroke. Genetic studies provide convincing evidence to support a
      causal relationship between sub-optimal B-vitamin status and CVD. People
      homozygous for the common C677T variant in the gene encoding the folate
      metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR), typically have
      a 14-21% higher risk of CVD. Apart from folate, riboflavin is required as a co
      factor for MTHFR. New evidence shows that riboflavin intervention results in
      marked lowering of blood pressure, specifically in patients with the MTHFR 677TT
      genotype. This novel gene-nutrient interaction may provide insights as to the
      mechanism that links C(1) metabolism with CVD outcomes.

PMID- 22152929
TI  - [From exercise physiology to medical decision].

PMID- 22152928
TI  - Seasonality of Clostridium difficile infections in Southern Germany.
AB  - Between 2000 and 2009, the total number of patients with Clostridium difficile
      infections increased considerably in Southeastern Germany. A clear seasonality
      was observed with a higher number of affected patients occurring in the winter
      months (January-March). Moxifloxacin and erythromycin-resistant C. difficile PCR
      ribotypes 001 (72%) and 027 (4.6%) were the most commonly isolated strains.

PMID- 22152930
TI  - [CT imaging of chronic interstitial lung diseases: from diagnosis to automated
      quantification].
AB  - Computed tomography is important for the diagnosis and follow-up of chronic
      diffuse interstitial lung diseases. Image quality has improved from each
      generation of scanner to the next and this continues to allow a better
      characterization of extent of pathology, or even the nature of the pathological
      process (potentially reversible inflammatory lesions compared to fibrotic
      lesions). The diagnostic imaging approach has evolved at the same time as
      technological developments. We initially thought in terms of the predominant
      lesions (nodular, alveolar consolidation, ground-glass opacity), and then moved
      to reasoning based on patterns, which are a combination of several elementary
      lesions (typically for the diagnosis of idiopathic pulmonary fibrosis). Nowadays,
      studies are focused on building models characterizing a specific disease and
      which combine several distinct patterns (typically for ground-glass opacity
      analysis). CT also allows a quantification of the extent of lung disease, which
      is linked to the prognosis of the disease and helps to monitor its progression.
      This quantification is usually based on visual criteria, the principles of which
      are summarized here. The development of automated quantification software could
      in the near future, be a support for the radiologist.

PMID- 22152931
TI  - [Anti-angiogenic factors in thoracic oncology: successes, failures and
      prospects].
AB  - Many growth factors involved in tumor angiogenesis are potential targets in
      thoracic oncology. This work is a review of the literature on the effectiveness
      of anti-angiogenic treatments in non-small cell lung cancer (NSCLC), small cell
      lung cancer (SCLC) and malignant pleural mesothelioma (MM). Thirty-four articles
      and 15 abstracts were identified. Currently, bevacizumab is the only drug that
      has demonstrated an impact on overall survival in first line treatment for stage
      IV non-squamous NSCLC, but VEGFR-TKI such as cediranib, aflibercept, vandetanib,
      pazopanib have shown encouraging results in phase II or III clinical trials. In
      extensive-disease SCLC and inoperable MM, bevacizumab is the most studied
      molecule, but again, clinical trials are still ongoing. Current data on potential
      predictors for efficacy are disappointing, but some biomarkers or radiological
      techniques might be useful for guiding the use of anti-angiogenic therapies in
      the future. In conclusion, bevacizumab is the most studied anti-angiogenic agent
      in thoracic oncology. It is the only approved drug with an indication in first
      line and maintenance treatment for stage IV non-squamous NSCLC. The indications
      for the use of VEGFR-TKI in clinical practice remain to be defined.

PMID- 22152932
TI  - [Follow-up of subjects occupationally exposed to asbestos, what are the
      objectives, the benefits, and the possible risks?].
AB  - The follow-up of workers occupationally exposed to asbestos has two possible
      beneficial effects: (1) individually, both medical by screening for diseases
      related to asbestos and social by notification of occupational disease and/or
      compensation from the indemnity funds for asbestos victims; (2) collectively, by
      the establishment of epidemiological surveillance (follow-up of cohorts) and
      evaluation of the impact of follow-up in terms of health benefits and
      compensation. The respiratory disorders related to asbestos are: cancer
      (malignant pleural mesothelioma and bronchial carcinoma), asbestos-related
      pulmonary fibrosis, and pleural disease (plaques, pleural fibrosis and benign
      pleurisy). In the light of the data currently available and the effectiveness of
      the tools used, medical and public health benefits of screening for mesothelioma
      have not been demonstrated. The early diagnosis of primary bronchial carcinoma
      can theoretically improve the prognosis of the subjects screened, particularly by
      identification of stage I disease on CT (pulmonary nodules). This is a common
      finding but there are a large number of false-positives. While we await the
      results of several international randomised trials, the benefits of a screening
      programme for bronchial carcinoma in the population at risk have not been
      demonstrated. There is no effective treatment for asbestosis but this is an
      independent risk factor for bronchial carcinoma and it is evidence of heavy
      asbestos exposure. Stopping smoking in subjects suffering from asbestosis will
      reduce the incidence of bronchial carcinoma. There is no effective treatment for
      asbestos-related benign pleural diseases but these are markers of exposure. The
      presence of pleural plaques has not been shown to be an aetiological factor for
      thoracic cancers. Post-occupational follow-up may involve risks to health,
      particularly repeated irradiation and invasive diagnostic procedures. It is also
      necessary to consider the psychological consequences inherent in all screening
      programmes. In conclusion, post-occupational follow-up might reduce the mortality
      of lung cancer by screening for localised disease and its incidence by a targeted
      anti-smoking programme. The theoretical benefits, that have not yet been
      demonstrated, have to be seen in perspective with the risks to physical and
      psychological health related to both screening and diagnostic procedures.

PMID- 22152933
TI  - [A simple view on lung cancer biology: the MET pathway].
AB  - MET is a cell membrane tyrosine kinase receptor for its ligand the hepatocyte
      growth factor (HGF), also called scatter factor (SF). MET conveys mitogenic,
      motogenic and proangiogenic signals, important during embryonic development and
      during the development of cancer. Activation of the HGF-MET pathway seems to be
      associated with a poor prognosis in lung cancer. Activation in lung cancer may be
      related to several molecular anomalies: ligand overexpression, receptor
      overexpression, genomic amplification or MET mutation. In MET amplified or
      mutated lung cancer, MET may be an important oncogene, as the tumor appears "MET
      addicted". In other lung cancers, MET may be implicated in tumour progression by
      tissue invasion and formation of metastases. MET amplification is also a
      mechanism known to be implicated in 20% of secondary resistance to EGFR
      inhibitors in patients presenting EGFR mutated lung cancer. Different strategies
      of MET inhibition in lung cancer are being studied, particularly in EGFR mutated
      lung cancer. In this review we discuss the structure of the MET receptor, the
      activated pathways, the main genomic anomalies in lung cancer and the development
      of MET inhibitors.

PMID- 22152934
TI  - [Diaphragm and skeletal muscle dysfunction in COPD].
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is often accompanied
      by skeletal muscle alterations, resulting in enhanced morbidity and mortality.
      STATE OF THE ART: Many studies have highlighted important structural and
      biochemical modifications in limb and respiratory muscles in COPD. Reviewing the
      similarities and differences between the two most studied muscles in COPD, the
      quadriceps and the diaphragm, may provide important clues about the mechanisms
      dictating muscle changes that occur in this disease. PERSPECTIVES: Though these
      two muscle groups share a common systemic environment, discrepancies are observed
      in their respective alterations. These phenotypic differences suggest that, in
      addition to systemic factors, the local microenvironment must participate in the
      reorganization seen in these two muscles in COPD. CONCLUSIONS: The current review
      introduces the alterations observed in the quadriceps and diaphragm in the
      context of COPD and suggests possible signaling pathways involved in the
      development of muscle dysfunction.

PMID- 22152935
TI  - [The optimal duration of anticoagulant treatment following pulmonary embolism].
AB  - The optimal course of oral anticoagulant therapy is determined according to the
      risk of recurrent venous thromboembolism after stopping therapy and the risk of
      anticoagulant-related bleeding. Clinical risk factors appear to be important in
      predicting the risk of recurrence whereas the influence of biochemical and
      morphological tests is uncertain. The risk of recurrent venous thromboembolism is
      low when the initial episode was provoked by a reversible major risk factor
      (surgery): 3 months of anticoagulation is sufficient. Conversely, the risk is
      high when venous thromboembolism was unprovoked or associated with persistent
      risk factor (cancer): 6 months or more prolonged anticoagulation is necessary.
      After this first estimation, the duration of anticoagulation may be modulated
      according to the presence or absence of certain additional risk factors (major
      thrombophilia, chronic pulmonary hypertension, massive pulmonary embolism): 6
      months if pulmonary embolism was provoked and 12 to 24 months if pulmonary
      embolism was unprovoked. If the risk of anticoagulant-related bleeding is high,
      the duration of anticoagulation should be shortened (3 months if pulmonary
      embolism was provoked and 3 to 6 months if it was unprovoked). Lastly, if
      pulmonary embolism occurred in association with cancer, anticoagulation should be
      conducted for 6 months or more if the cancer is active or treatment is on going.
      Despite an increasing knowledge of the risk factors for recurrent venous
      thromboembolism, a number of issues remain unresolved. Randomised trials
      comparing different durations of anticoagulation are needed.

PMID- 22152936
TI  - [Muscle activity and energy expenditure].
AB  - Most of increases in energy metabolism are induced by exercise. They are related
      with power and efficiency. In cycle ergometer exercise efficiency is positively
      correlated with exercise power and negatively correlated with pedaling rate. Ramp
      exercises are associated with an apparent increase in efficiency. Movements of
      daily life activity are too complex to make evaluation of power or efficiency
      possible. Energy expenditure assessment is based on direct measurement of the
      energy metabolism increase. The energy cost of movement or economy is calculated.
      Daily activity recording provides an assessment of the energy metabolism ability
      of patients. Muscle contractile activity is linked with ATP splitting. The
      pathways to resynthesize ATP include anaerobic glycogenolysis and the aerobic
      breakdown of substrates. Type I fibres have a higher oxidative capacity than type
      II fibres. Type II fibres demonstrate a higher glycolytic capacity, contract
      faster, and are more fatigable. Information relative to energy expenditure during
      daily life activity allows clinicians to better assess the clinical implications
      of the stress tests results.

PMID- 22152937
TI  - [Diagnosis and treatment of atypical mycobacterial infections of the respiratory
      tract].
AB  - INTRODUCTION: Non tuberculous mycobacteria (NTM), unlike tuberculous
      mycobacteria, are not strictly human pathogens. The diagnosis of infection and
      the choice of treatment remain difficult. BACKGROUND: Evidence of a NTM in a
      pulmonary sample is not synonymous with infection. The diagnosis depends on the
      association of clinical, radiological and microbiological factors. If a NTM is
      isolated from a respiratory sample, the probability of infection depends on the
      species. The main NTMs responsible for pulmonary infection in France are
      Mycobacterium avium intracellulare, Mycobacterium xenopi, Mycobacterium kansasi
      and Mycobacterium abscessus. Their management is difficult and poorly understood.
      Treatment is well established for M. avium intracellulare and M. kansasii, with
      combinations of clarithromycin-rifampicin-ethambutol and isoniazid-rifampicin
      ethambutol respectively. For M. xenopi, the optimal treatment is not known and a
      combination of clarithromycin-rifampicin-ethambutol, with moxifloxacin as an
      alternative, is currently recommended. In general, treatment is prolonged and
      often associated with problems of tolerance. VIEWPOINT AND CONCLUSION: The
      management of NTM infection, taking into account of the increase in patients "at
      risk", is an important issue. Further studies are needed to improve the criteria
      for infection and to find the optimal therapeutic combinations.

PMID- 22152938
TI  - [New diagnostic tests for tuberculosis in southern countries: from theory to
      practice in southern countries].
AB  - INTRODUCTION: Tuberculosis (TB) is responsible of 1.7 millions of deaths per year
      worldwide. In high burden countries sputum smear-microscopy diagnoses only half
      of the cases of pulmonary TB. It is unlikely that a new test will replace smear
      microscopy in peripheral services in the short term. BACKGROUND: Between 2007 and
      2009 WHO recommended the introduction of seven new tests or diagnostic approaches
      for high burden countries, for peripheral laboratories : 1) the optimisation of
      smear-microscopy using the revised smear-positive case definitions; 2)
      examination of two specimens instead of three; 3) examination of two specimens
      collected on the same day; 4) the use of light-emitting diode based fluorescence
      microscopy and for reference laboratories: 5) the use of liquid medium culture;
      6) the use of rapid antigenic identification tests; 7) the rapid detection of
      rifampicin resistance. VIEWPOINTS: The recent development of a fully automated
      nucleic acid amplification test for both TB detection and detection of rifampicin
      resistance will soon improve the diagnosis of TB in HIV infected patients outside
      reference laboratories in high burden countries. CONCLUSION: Despite the recent
      advances in TB diagnosis, there is need for more research to develop point of
      care tests that do not depend on sputum specimens, that are practicable at
      peripheral units and that are highly sensitive in HIV infected patients and
      children.

PMID- 22152939
TI  - [Asthmatic exacerbations: specific features in children].
AB  - Asthma concerns more than 10% of 10-year-old children. Despite the similarities
      between adult and childhood asthma, the pediatric population presents some
      specific characteristics, notably in relation to exacerbations. Asthma in the
      newborn infant is a specific entity, the definition of which has recently been
      officially recognized. In exacerbations, the most important trigger factors are
      respiratory virus infections, the strain having prognostic importance. The indoor
      and outdoor environments are risk factors, particularly high levels of
      atmospheric pollution. Nutrients seem to play a prognostic role through vitamin D
      or food allergy. Measurement of exhaled nitric oxide and examination of induced
      sputum may help in diagnosis and adjustment of treatment but these tools are not
      yet effective as predictive factors in asthma exacerbations. Prevention, early
      management and continued education of children and their families remain the best
      methods to improve asthma control.

PMID- 22152940
TI  - [Adult respiratory sequelae of premature birth].
AB  - INTRODUCTION: Between 5 and 7% of babies are born prematurely. In the paediatric
      age group, the respiratory morbidity of these patients is well known,
      particularly in cases of bronchopulmonary dysplasia (BPD). On the other hand,
      very few data are available concerning their adult respiratory status.
      BACKGROUND: There are currently three different groups of ex-premature babies:
      (1) those with no BPD who are usually not considered as respiratory high-risk
      adults but have not been well studied; (2) ex-premature babies with BPD who have
      an increased risk of asthma, respiratory infections, bronchial obstruction
      aggravated by smoking, and non-atopic bronchial hyperreactivity; this group has
      been well studied but not beyond 30 years of age; (3) the babies born very
      prematurely and affected with a new form of BPD due to neonatal intensive care at
      a very immature stage of pulmonary development, and for whom the future in adult
      life is unknown but worrying because of reduced lung volumes since birth.
      VIEWPOINTS AND CONCLUSIONS: The respiratory physician must be aware of these
      groups of adults who he may encounter and who may develop, sooner or later, a
      certain type of chronic obstructive pulmonary disease.

PMID- 22152941
TI  - [Treatment of distal airways involvement in COPD].
AB  - INTRODUCTION: The current pharmacological treatment of COPD provides only partial
      beneficial effects on symptoms, exercise tolerance, frequency of exacerbations
      and quality of life. This could be related to poor targeting of the distal
      airways by current treatments, yet these airways are particularly involved in
      airflow obstruction and its consequences such as hyperinflation. BACKGROUND: Many
      treatments used in COPD could have effects on distal airways, including
      bronchodilators, corticosteroids, mucolytics and antibiotics. However, these
      possible effects remain poorly understood. VIEWPOINTS: New treatments targeting
      more specifically the mechanisms of inflammation, oxidative stress and tissue
      remodeling that characterize COPD, could prove useful in its management, but most
      are still only in the early stages of their development. Advances could also come
      from improvements in inhalation devices, delivering more of the medication to the
      distal airways. CONCLUSIONS: Improvement in the management of COPD could come
      from progress in terms of both molecules and their mode of administration.

PMID- 22152942
TI  - Prospective randomized comparison of conventional instruments and the Harmonic
      Focus((r)) device in breast-conserving therapy for primary breast cancer.
AB  - BACKGROUND: In recent years, surgeons have utilized Harmonic instruments to
      perform breast cancer resection. Retrospective and prospective studies have
      demonstrated that the use of this surgical device for mastectomy and axillary
      dissection can reduce perioperative blood loss, seroma formation, and duration
      and total amount of drainage. No study has analyzed the feasibility of Harmonic
      instruments in breast-conserving surgery. We conducted a prospective, randomized
      clinical trial comparing Harmonic instrument and conventional surgery in the
      performance of breast-conserving surgery and axillary procedures to determine
      differences in surgical procedures, postoperative outcome, and complications.
      METHODS: One hundred and six patients with operable breast cancer who underwent
      breast-conserving surgery at a single institution between December 2009 and
      January 2011 were included in the analysis. Surgery was performed in 52 patients
      with the Harmonic Focus((r)) device and in 54 with scissors and electrocautery.
      This study focused on operative time, drainage volume, and postoperative outcome
      measures like blood loss, surgery related complications and patient-reported
      postoperative pain. RESULTS: We found a multivariable independent influence in
      axillary seroma formation and volume of breast drainage with HS. Evident
      difference in volume and duration of axillary and breast drainage, subjective and
      objective postoperative pain, reduction in serum hemoglobin, size and weight of
      resected breast tissue and length of hospital stay in favor of the Harmonic
      instrument could also be shown. DISCUSSION: The Harmonic instrument provides key
      benefits in surgical technique, postoperative outcome, and complication rates in
      breast cancer surgery.

PMID- 22152943
TI  - Objectively measured breast symmetry has no influence on quality of life in
      breast cancer patients.
AB  - AIMS: This study investigates how quality of life (QoL) of breast cancer patients
      is related to breast symmetry. METHODS: We objectively measured breast symmetry
      using the breast analyzing tool (BAT) in 101 patients after breast conserving
      surgery for breast cancer at different time points during follow up. We
      correlated the results with the quality of life measured at the same time using
      the breast image scale (BIS), the EORTC QLQ-BR23 scale and a not validated sexual
      score scale. Age, tumour size, tumour/breast relation and the use of oncoplastic
      surgery were also correlated with symmetry and quality of life scales. Using
      multivariate analyses, independent parameters for an improved quality of life
      were identified. RESULTS: Mean age was 56 (+/-11.6), and 75.2% of patients had T1
      or T2 tumours. Patient age (p = 0.03) and tumour size (p = 0.01) significantly
      influenced objectively measured breast symmetry. The cosmetic result was
      important for 53% of patients while 48% found it not important. Independent from
      this, neither overall quality of life nor breast self esteem was influenced by
      breast symmetry in our patients. CONCLUSIONS: After breast cancer surgery, breast
      symmetry is not a major factor for patients' quality of life and breast self
      esteem. Cosmetic result seems to be less important than oncologic outcome in
      patients with breast cancer.

PMID- 22152944
TI  - Re: role of robot-assisted laparoscopy in adjuvant surgery for locally advanced
      cervical cancer (EJSO 2010; 36(4):409-413) by Lambaudie E. et al.

PMID- 22152945
TI  - Regulation of BMP activity and range in Drosophila wing development.
AB  - Bone morphogenetic protein (BMP) signaling controls development and maintenance
      of many tissues. Genetic and quantitative approaches in Drosophila reveal that
      ligand isoforms show distinct function in wing development. Spatiotemporal
      control of BMP patterning depends on a network of extracellular proteins Pent,
      Ltl and Dally that regulate BMP signaling strength and morphogen range. BMP
      mediated feedback regulation of Pent, Ltl, and Dally expression provides a system
      where cells actively respond to, and modify, the extracellular morphogen
      landscape to form a gradient that exhibits remarkable properties, including
      proportional scaling of BMP patterning with tissue size and the modulation of
      uniform tissue growth. This system provides valuable insights into mechanisms
      that mitigate the influence of variability to regulate cell-cell interactions and
      maintain organ function.

PMID- 22152947
TI  - Biomaterials for the treatment of myocardial infarction: a 5-year update.
AB  - The first review on biomaterials for the treatment of myocardial infarction (MI)
      was written in 2006. In the last 5 years, the general approaches for biomaterial
      treatment of MI and subsequent left ventricular remodeling remain the same,
      namely, left ventricular restraints, epicardial patches, and injectable
      therapies. Nonetheless, there have been significant developments in this field,
      including advancement of biomaterial therapies to large animal pre-clinical
      studies and, more recently, to clinical trials. This review focuses on the
      progress made in the field of cardiac biomaterial treatments for MI over the last
      5 years.

PMID- 22152946
TI  - Putting structure into context: fitting of atomic models into electron
      microscopic and electron tomographic reconstructions.
AB  - A complete understanding of complex dynamic cellular processes such as cell
      migration or cell adhesion requires the integration of atomic level structural
      information into the larger cellular context. While direct atomic-level
      information at the cellular level remains inaccessible, electron microscopy,
      electron tomography and their associated computational image processing
      approaches have now matured to a point where sub-cellular structures can be
      imaged in three dimensions at the nanometer scale. Atomic-resolution information
      obtained by other means can be combined with this data to obtain three
      dimensional models of large macromolecular assemblies in their cellular context.
      This article summarizes some recent advances in this field.

PMID- 22152948
TI  - A point-of-care platelet function assay and C-reactive protein for prediction of
      major cardiovascular events after drug-eluting stent implantation.
AB  - OBJECTIVES: This study sought to investigate clinical utility of on-site platelet
      function test and C-reactive protein (CRP) in patients undergoing percutaneous
      coronary intervention (PCI). BACKGROUND: Data on long-term prognostic value of
      high on-treatment platelet reactivity (HTPR) on clopidogrel after PCI are
      limited. As a distinct biological pathway, CRP has been suggested to be
      associated with post-PCI atherothrombotic events. METHODS: We evaluated 2,849
      patients who received drug-eluting stents (DES) and had post-PCI VerifyNow P2Y12
      assays (Accumetrics, San Diego, California) performed. Among them, baseline CRP
      measurement was available in 2,546 patients. The primary endpoint was a composite
      of all-cause death, nonfatal myocardial infarction, stent thrombosis, and stroke.
      RESULTS: During follow-up (median, 2.2 years), the occurrence of the primary
      endpoint did not significantly differ among patients with and without HTPR (2.8%
      vs. 2.4% at 2 years; hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.88
      to 2.01; p = 0.18). By contrast, patients with elevated CRP levels were at
      significantly higher risk for the primary endpoint, as compared with those with
      nonelevated CRP levels (5.6% vs. 1.7% at 2 years; HR: 2.81, 95% CI:, 1.83 to
      4.31; p < 0.001). The VerifyNow test had no incremental usefulness to classify
      long-term risk. However, the incorporation of CRP into a model with conventional
      clinical and procedural risk factors significantly improved the C-statistic for
      the prediction of the primary endpoint (0.729 to 0.759; p = 0.03). CONCLUSIONS:
      We failed to identify that HTPR measured by VerifyNow P2Y12 assay was
      significantly associated with long-term atherothrombotic risks in patients
      receiving DES. However, elevated CRP levels were significantly associated with
      worse outcomes and had incremental predictive values over conventional risk
      factors.

PMID- 22152949
TI  - Personalized therapy following drug-eluting stenting using platelet function
      testing and C-reactive protein.

PMID- 22152950
TI  - Impact of body weight and extreme obesity on the presentation, treatment, and in
      hospital outcomes of 50,149 patients with ST-Segment elevation myocardial
      infarction results from the NCDR (National Cardiovascular Data Registry).
AB  - OBJECTIVES: The aim of this study was to assess the impact of extreme (class III)
      obesity (body mass index [BMI] >=40 kg/m(2)) on care and outcomes in patients
      with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Although its
      prevalence is increasing rapidly, little is known about the impact of extreme
      obesity on STEMI presentation, treatments, complication rates, and outcomes.
      METHODS: The relationship between BMI and baseline characteristics, treatment
      patterns, and risk-adjusted in-hospital outcomes was quantified for 50,149
      patients with STEMI from the National Cardiovascular Data Registry (NCDR) ACTION
      Registry-GWTG. RESULTS: The proportions of patients with STEMI by BMI category
      were as follows: underweight (BMI <18.5 kg/m(2)) 1.6%, normal weight (18.5
      kg/m(2) <=BMI <25 kg/m(2)) 23.5%, overweight (25 kg/m(2) <=BMI <30 kg/m(2))
      38.7%, class I obese (30 kg/m(2) <=BMI <35 kg/m(2)) 22.4%, class II obese (35
      kg/m(2) <=BMI <40 kg/m(2)) 8.7%, and class III obese 5.1%. Extreme obesity was
      associated with younger age at STEMI presentation (median age 55 years for class
      III obese vs. 66 years for normal weight); a higher prevalence of diabetes,
      hypertension, and dyslipidemia; a lower prevalence of smoking; and less extensive
      coronary artery disease and higher left ventricular ejection fraction. Process-of
      care measures were similar across BMI categories, including the extremely obese.
      Using class I obesity as the referent, risk-adjusted in-hospital mortality rates
      were significantly higher only for class III obese patients (adjusted odds ratio:
      1.64; 95% confidence interval: 1.32 to 2.03). CONCLUSIONS: Patients with extreme
      obesity present with STEMI at younger ages and have less extensive coronary
      artery disease, better left ventricular systolic function, and similar processes
      and quality of care. Despite these advantages, extreme obesity remains
      independently associated with higher in-hospital mortality.

PMID- 22152951
TI  - Impact of obesity on outcomes in myocardial infarction combating the "obesity
      paradox".

PMID- 22152952
TI  - High-sensitivity C-reactive protein is within normal levels at the very onset of
      first ST-segment elevation acute myocardial infarction in 41% of cases: a
      multiethnic case-control study.
AB  - OBJECTIVES: This study sought to assess the prevalence of normal levels of high
      sensitivity C-reactive protein (hsCRP) at the very onset of ST-segment elevation
      myocardial infarction (STEMI). BACKGROUND: Levels of hsCRP >=2 mg/l identify
      individuals who benefit from lipid lowering and possibly anti-inflammatory
      agents, but how many patients develop infarction in spite of hsCRP levels <2 mg/l
      and thus would be ineligible for these treatments? METHODS: We studied 887
      patients with unequivocally documented STEMI as the first manifestation of
      coronary disease and 887 matched control subjects from urban areas of Italy,
      Scotland, and China. Blood samples were obtained before reperfusion strategies <6
      h from symptoms onset in order to limit acute event-related increases. RESULTS:
      hsCRP values were similar in samples obtained <2 h, 2 to 4 h, and 4 to 6 h from
      symptoms onset in all ethnic groups, consistent with the delayed hsCRP elevation
      after myocardial necrosis and thus indicative of pre-infarction levels. Median
      hsCRP values were significantly higher in patients than in control subjects: 2.49
      (interquartile range [IQR]: 1.18 to 5.55) mg/l versus 1.32 (IQR: 0.58 to 3.10)
      mg/l (p < 0.0001), which is consistent with previous findings. However, 41% of
      patients had hsCRP levels <2 mg/l and conversely, 37% of control subjects had
      values >=2 mg/l. CONCLUSIONS: The measurement of hsCRP, with a 2 mg/l cutoff,
      would not have predicted 41% of unequivocally documented STEMIs in 3 ethnic
      groups without evidence of previous coronary disease, thus indicating both its
      limitations as an individual prognostic marker and as an indicator of a
      generalized inflammatory pathogenetic component of STEMI. New specific prognostic
      and therapeutic approaches should be found for such a large fraction of patients
      at risk.

PMID- 22152953
TI  - C-reactive protein and ST-segment elevation myocardial infarction discordance.

PMID- 22152954
TI  - Comparison of surgical, stent, and balloon angioplasty treatment of native
      coarctation of the aorta: an observational study by the CCISC (Congenital
      Cardiovascular Interventional Study Consortium).
AB  - OBJECTIVES: The purpose of this study was to compare the safety and efficacy of
      surgical, stent, and balloon angioplasty (BA) treatment of native coarctation
      acutely and at follow-up. BACKGROUND: Controversy surrounds the optimal treatment
      for native coarctation of the aorta. This is the first multicenter study
      evaluating acute and follow-up outcomes of these 3 treatment options in children
      weighing >10 kg. METHODS: This is a multicenter observational study. Baseline,
      acute, short-term (3 to 18 months), and intermediate (>18 months) follow-up
      hemodynamic, imaging data, and complications were recorded. RESULTS: Between June
      2002 and July 2009, 350 patients from 36 institutions were enrolled: 217
      underwent stent, 61 underwent BA, and 72 underwent surgery. All 3 arms showed
      significant improvement acutely and at follow-up in resting systolic blood
      pressure and upper to lower extremity systolic blood pressure gradient (ULG).
      Stent was superior to BA in achieving lower ULG acutely. Surgery and stent were
      superior to BA at short-term follow-up in achieving lower ULG. Stent patients had
      shorter hospitalization than surgical patients (2.4 vs. 6.4 days; p < 0.001) and
      fewer complications than surgical and BA patients (2.3%, 8.1%, and 9.8%; p <
      0.001). The BA patients were more likely to encounter aortic wall injury, both
      acutely and at follow-up (p < 0.001). CONCLUSIONS: Stent patients had
      significantly lower acute complications compared with surgery patients or BA
      patients, although they were more likely to require a planned reintervention. At
      short-term and intermediate follow-up, stent and surgical patients achieved
      superior hemodynamic and integrated aortic arch imaging outcomes compared with BA
      patients. Because of the nonrandomized nature of this study, these results should
      be interpreted with caution.

PMID- 22152955
TI  - Genetic susceptibility to coronary heart disease in type 2 diabetes: 3
      independent studies.
AB  - OBJECTIVES: The aim of this study was to evaluate whether coronary heart disease
      (CHD)-susceptibility loci identified by genome-wide association studies of the
      general population also contribute to CHD in type 2 diabetes. BACKGROUND: No
      study has examined the effects of these genetic variants on CHD in diabetic
      patients. METHODS: We genotyped 15 genetic markers of 12 loci in 3 studies of
      diabetic patients: the prospective Nurses' Health Study (309 CHD cases, and 544
      control subjects) and Health Professional Follow-up Study (345 CHD cases, and 451
      control subjects) and the cross-sectional Joslin Heart Study (422 CHD cases, and
      435 control subjects). RESULTS: Five single-nucleotide polymorphisms, rs4977574
      (CDKN2A/2B), rs12526453 (PHACTR1), rs646776 (CELSR2-PSRC1-SORT1), rs2259816
      (HNF1A), and rs11206510 (PCSK9) showed directionally consistent associations with
      CHD in the 3 studies, with combined odds ratios (ORs) ranging from 1.17 to 1.25
      (p = 0.03 to 0.0002). None of the other single-nucleotide polymorphisms reached
      significance in individual or combined analyses. A genetic risk score (GRS) was
      created by combining the risk alleles of the 5 significantly associated loci. The
      OR of CHD/GRS unit was 1.19 (95% confidence interval: 1.13 to 1.26; p < 0.0001).
      Individuals with GRS >=8 (19% of diabetic subjects) had almost a 2-fold increase
      in CHD risk (OR: 1.94, 95% confidence interval: 1.60 to 2.35) as compared with
      individuals with GRS <=5 (30% of diabetic subjects). Prediction of CHD was
      significantly improved (p < 0.001) when the GRS was added to a model including
      clinical predictors in the combined samples. CONCLUSIONS: Our results illustrate
      the consistency and differences in the determinants of genetic susceptibility to
      CHD in diabetic patients and the general populations.

PMID- 22152957
TI  - Beta3-adrenoceptor activation just says NO to myocardial reperfusion injury.

PMID- 22152956
TI  - Beta3-adrenoreceptor stimulation ameliorates myocardial ischemia-reperfusion
      injury via endothelial nitric oxide synthase and neuronal nitric oxide synthase
      activation.
AB  - OBJECTIVES: This paper examined whether nebivolol protects the heart via nitric
      oxide (NO) synthase and NO-dependent signaling in an in vivo model of acute
      myocardial infarction. BACKGROUND: Beta(3)-adrenergic receptor (AR) activation
      promotes endothelial nitric oxide synthase (eNOS) activity and NO
      bioavailability. We hypothesized that specific beta(3)-AR agonists would
      attenuate myocardial ischemia-reperfusion (MI/R) injury via eNOS activation and
      increased NO bioavailability. METHODS: Mice were subjected to 45 min of
      myocardial ischemia in vivo followed by 24 h of reperfusion (R). Nebivolol (500
      ng/kg), CL 316243 (1 MUg/kg), BRL-37344 (1 MUg/kg), or vehicle (VEH) was
      administered at the time of R. Myocardial area-at-risk (AAR) and infarct size
      (INF)/AAR was measured at 24 h of R. Cardiac tissue and plasma were collected to
      evaluate eNOS phosphorylation, neuronal nitric oxide synthase (nNOS), inducible
      nitric oxide synthase expression, and nitrite and nitrosothiol levels. RESULTS:
      Nebivolol (500 ng/kg) reduced INF/AAR by 37% (p < 0.001 vs. VEH) and serum
      troponin-I levels from 41 +/- 4 ng/ml to 25 +/- 4 ng/ml (p < 0.05 vs. VEH). CL
      316243 and BRL-37344 reduced INF by 39% and 42%, respectively (p < 0.001 vs.
      VEH). Nebivolol and CL 316243 increased eNOS phosphorylation at Ser-1177 (p <
      0.05 vs. VEH) and increased nitrite and total nitrosylated protein levels.
      Nebivolol and CL 316243 significantly increased myocardial nNOS expression.
      Nebivolol failed to reduce INF after MI/R in beta(3)-AR (-/-), eNOS(-/-), and in
      nNOS(-/-) mice. CONCLUSIONS: Our results indicate that beta(3)-AR agonists
      protect against MI/R injury. Furthermore, the cardioprotective effects of beta(3)
      AR agonists are mediated by rapid eNOS and nNOS activation and increased NO
      bioavailability.

PMID- 22152958
TI  - Interferon-alpha in cardiac Erdheim-Chester disease.

PMID- 22152959
TI  - Delayed cardiac tamponade after radiofrequency catheter ablation of atrial
      fibrillation: a worldwide report.

PMID- 22152960
TI  - Late gadolinium enhancement in left ventricular dysfunction after trastuzumab.

PMID- 22152961
TI  - Clinical risk stratification of chemotherapy-induced cardiac dysfunction.

PMID- 22152962
TI  - Early identification of left ventricular dysfunction induced by trastuzumab.

PMID- 22152964
TI  - Cardiovascular risk assessment of liver transplantation candidates.

PMID- 22152965
TI  - The role of platelet function testing and genotyping in the stented patient
      treated with clopidogrel.

PMID- 22152968
TI  - Automatically segmented DynaCT: enhanced imaging during transcatheter aortic
      valve implantation.

PMID- 22152969
TI  - Influence of diabetes mellitus on clinical outcomes following primary
      percutaneous coronary intervention in patients with ST-segment elevation
      myocardial infarction.
AB  - Patients with diabetes mellitus (DM) have a worse outcome after percutaneous
      coronary intervention (PCI) than nondiabetic patients. The purpose of this study
      was to compare rates of stent thrombosis, myocardial infarction (MI), target
      lesion revascularization (TLR), and death in diabetic and nondiabetic patients
      treated with primary PCI for ST-segment elevation MI (STEMI) in Western Denmark.
      From January 2002 through June 2005, 3,655 consecutive patients with STEMI
      treated with primary PCI and stent implantation (316 patients with DM, 8.6%;
      3,339 patients without DM, 91.4%) were recorded in the Western Denmark Heart
      Registry. All patients were followed for 3 years. Cox regression analysis was
      used to compute hazard ratios (HRs), controlling for potential confounding. Three
      year rates of definite stent thrombosis were 1.6% in the DM group and 1.5% in the
      non-DM group (adjusted HR 1.15, 95% confidence interval [CI] 0.50 to 2.67). The
      rate of MI was 12.3% in the DM group versus 5.6% in the non-DM group (adjusted HR
      2.56, 95% CI 1.81 to 3.61). Rates of TLR were 12.1% in the DM group and 8.7% in
      the non-DM group (adjusted HR 1.55, 95% CI 1.14 to 2.11). All-cause mortality was
      23.7% in patients with DM versus 12.7% in patients without DM (adjusted HR 2.03,
      95% CI 1.59 to 2.59). In conclusion, stent thrombosis rate was similar in
      patients with and without DM and STEMI treated with primary PCI, whereas the
      presence of DM increased the risk of MI, TLR, and death.

PMID- 22152970
TI  - Commonality between depression and heart failure.
AB  - Heart failure (HF) and depression are debilitating diseases with significant
      effects on functional status and real and perceived quality of life. Despite many
      advances in therapy for HF mortality remains high. Depression and HF have been
      recognized to coexist but this does not imply a causative relation. Depressed
      patients develop more symptoms, have worse compliance with medication regimens,
      are slower to return to work and social activities, and seem to have a poorer
      quality of life. In patients with known cardiac disease depression also predicts
      future events independent of disease severity and other risk factors such as
      smoking or diabetes mellitus. In conclusion, this review attempts to address the
      cause/effect relation, if any, between HF and depression and the role of
      treatment of depression in the setting of HF.

PMID- 22152971
TI  - Meta-analysis of prospective randomized controlled trials comparing intracoronary
      versus intravenous abciximab in patients with ST-elevation myocardial infarction
      undergoing primary percutaneous coronary intervention.
AB  - Abciximab is a glycoprotein IIb/IIIa receptor inhibitor that has been shown to
      improve outcomes in patients with ST-segment elevation myocardial infarction who
      undergo primary percutaneous coronary intervention (pPCI). An earlier study
      reported better efficacy with intracoronary (IC) compared to intravenous (IV)
      administration, but this finding has not been duplicated in other studies, thus
      leaving a great deal of uncertainty as to the most efficacious route of
      administration. To investigate if IC abciximab compared to IV administration
      decreases mortality and major adverse cardiac events in patients with ST-segment
      elevation myocardial infarction who undergo pPCI, a meta-analysis was performed
      consisting only of prospective randomized controlled trials. Subgroup analysis
      was performed to investigate the source of difference in efficacy between the 2
      strategies. A meta-analysis of 4 trials including 1,148 subjects revealed that IC
      abciximab significantly reduced mortality compared to IV administration (1.5% vs
      3.6%, odds ratio 0.44, 95% confidence interval 0.20 to 0.95, p = 0.04). Major
      adverse cardiac events were also reduced in a subgroup in which <30% of patients
      received aspiration thrombectomy (6.1% vs 16.2%, odds ratio 0.33, 95% confidence
      interval 0.18 to 0.61, p = 0.0004). In conclusion, the totality of the data
      available from relatively small but high-quality studies shows a significant
      mortality reduction associated using IC abciximab for pPCI compared to IV
      abciximab. IC abciximab in the setting of pPCI for ST-segment elevation
      myocardial infarction may be beneficial for patients with higher risk profiles.

PMID- 22152972
TI  - Comparison of left atrial volume parameters in detecting left ventricular
      diastolic dysfunction versus tissue Doppler recordings.
AB  - Because of diastolic coupling between the left atrium and left ventricle, we
      hypothesized that left atrial (LA) function mirrors the diastolic function of
      left ventricle. The aims of this study were to assess whether LA volume
      parameters can be good indexes of left ventricular diastolic dysfunction. Six
      hundred fifty-nine patients underwent cardiac catheterization and measurements of
      left ventricular filling pressure (LVFP). Echocardiographic examinations
      including tissue Doppler and LA volumes were also assessed. Ratio of early
      diastolic mitral inflow velocity to early diastolic mitral annular velocity and
      LVFP tended to increase after progression of diastolic dysfunction. The inverse
      phenomenon existed in LA ejection and LA distensibility. LA distensibility was
      superior to LA ejection fraction and early diastolic mitral inflow velocity/early
      diastolic mitral annular velocity for identifying LVFP >15 mm Hg (areas under
      receiver operating characteristic curve 0.868, 0.834, and 0.759, respectively)
      and for differentiating pseudonormal from normal diastolic filling (areas under
      receiver operating characteristic curve 0.962, 0.907, and 0.741, respectively).
      Multivariate logistic regression showed that LA ejection fraction and LA
      distensibility were associated significantly with the presence of
      pseudonormal/restrictive ventricular filling. In conclusion, LA volume parameters
      can identify LVFP >15 mm Hg and differentiate among patterns of ventricular
      diastolic dysfunction. For assessing diastolic function LA parameters offer
      better performance than even tissue Doppler.

PMID- 22152973
TI  - Comparison of clinical characteristics, treatments and outcomes of patients with
      ST-elevation acute myocardial infarction with versus without new or presumed new
      left bundle branch block (from NCDR(r)).
AB  - Guidelines recommend urgent reperfusion for patients with new left bundle branch
      block (LBBB), similar to patients with ST-segment elevation myocardial infarction
      (STEMI). However, there are limited contemporary data comparing these 2 groups of
      patients. Patients presenting with acute STEMI or presumed new LBBB (nLBBB)
      enrolled in the Acute Coronary Treatment and Intervention Outcomes Network
      (ACTION) Registry-Get With the Guidelines (GWTG) from January 2007 to March 2009
      were evaluated for clinical characteristics, treatment patterns, and outcomes.
      Logistic generalized estimating equation modeling was used to examine associated
      risk-adjusted mortality. Of 46,006 patients with either STEMI or nLBBB, 44,405
      (96.5%) had STEMI, and 1,601 (3.5%) had nLBBB. Overall, patients with nLBBB had
      more baseline co-morbidities compared to those with STEMI. Compared to patients
      with STEMI, those with nLBBB were less likely to receive acute reperfusion (93.9%
      vs 48.3% p <0.0001) and were less likely to have door-to-balloon times <=90
      minutes (76.8% vs 34.5%, p <0.0001). Mortality rates were higher for patients
      with nLBBB compared to those with STEMI (13.3% vs 5.6%, p <0.0001). After
      multivariate adjustment, nLBBB was not associated with an increased risk for in
      hospital mortality (odds ratio 0.91, 95% confidence interval 0.75 to 1.12, p =
      0.38). In conclusion, patients with nLBBB were clinically different from those
      with STEMI, with significantly more co-morbidities, and were less likely to
      receive emergent reperfusion therapy. Despite these differences, adjusted
      mortality rates were similar between patients with nLBBB and those with STEMI.

PMID- 22152974
TI  - Frequency and predictors of hyperkalemia in patients >=60 years of age with heart
      failure undergoing intense medical therapy.
AB  - Hyperkalemia is a concern in heart failure (HF), especially in older patients
      with co-morbidities. Previous studies addressing this issue have focused mainly
      on younger patients. This study was aimed at determining the frequency and
      predictors of hyperkalemia in older patients with HF undergoing intense medical
      therapy. Frequency and predictors of hyperkalemia were defined in patients (n =
      566) participating in the Trial of Intensified versus Standard Medical Therapy in
      Elderly Patients with Congestive Heart Failure, in which patients >=60 years of
      age were randomized to a standard versus an intensified N-terminal brain
      natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients
      (13.4%) had hyperkalemia (>=5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia
      (>=6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per
      mmol/L), baseline creatinine (OR 1.11 per 10 MUmol/L), gout (OR 2.56), New York
      Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher
      dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose
      changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg,
      OR 2.52; >25 mg, OR 3.24) were independent predictors for development of
      hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common
      in patients >=60 years of age with HF undergoing intense medical therapy. Risk is
      increased in patients treated with spironolactone, in addition to patient
      specific risk factors such as chronic kidney disease, higher serum potassium,
      advanced NYHA class, and gout. Careful surveillance of serum potassium and
      cautious use of spironolactone in patients at risk may help to decrease the
      incidence of potentially hazardous complications caused by hyperkalemia.

PMID- 22152975
TI  - Effect of anemia on short- and long-term outcome in patients hospitalized for
      acute coronary syndromes.
AB  - Anemia is common in hospitalized cardiac patients and is associated with adverse
      outcomes. The aim of this study was to identify the association of anemia with
      early and long-term outcomes in patients with acute coronary syndromes (ACSs).
      Included were 5,304 consecutive patients (73% men, 61 +/- 12 years of age)
      admitted to a coronary care unit from 1985 through 2008 for ACS. According to the
      World Health Organization, anemia was defined as serum hemoglobin levels <13 g/dl
      for men and <12 g/dl for women. Anemia was divided into tertiles to compare mild,
      moderate, and severe anemia to nonanemia. For trend analyses the study population
      was categorized in 3 groups: 1985 to 1990, 1991 to 2000, and 2001 to 2008.
      Outcome measurements were all-cause mortality at 30-days and 20 years. Anemia was
      present in 2,016 patients (38%), of whom 655 had mild anemia, 717 moderate
      anemia, and 646 severe anemia. Median follow-up duration was 10 years (range 2 to
      25). Compared to nonanemia, adjusted hazard ratios (HRs) for mortality at 30 days
      were 1.40 for moderate anemia (95% confidence interval [CI] 1.04 to 1.87) and
      1.67 for severe anemia (95% CI 1.25 to 2.24). At 20 years HRs were 1.13 for
      moderate anemia (95% CI 1.01 to 1.27) and 1.39 for severe anemia (95% CI 1.23 to
      1.56). In addition, survival during hospitalization improved over time. Compared
      to 1985 to 1990 adjusted HRs were 0.52 for 1991 to 2000 (95% CI 0.41 to 0.66) and
      0.36 for 2001 to 2008 (95% CI 0.25 to 0.51). In conclusion, presence and severity
      of anemia is an important predictor of higher in-hospital and long-term mortality
      after ACS. In addition, since the 1980s in-hospital outcome of patients with ACS
      and anemia has improved.

PMID- 22152976
TI  - Unprecedented furan-2-carbonyl C-glycosides and phenolic diglycosides from
      Scleropyrum pentandrum.
AB  - Five unprecedented furan-2-carbonyl C-glycosides, scleropentasides A-E, and two
      phenolic diglycosides, 4-hydroxy-3-methoxybenzyl 4-O-beta-D-xylopyranosyl-(1->6)
      beta-D-glucopyranoside and 2,6-dimethoxy-p-hydroquinone 1-O-beta-D-xylopyranosyl
      (1->6)-beta-d-glucopyranoside, were isolated from leaves and twigs of Scleropyrum
      pentandrum together with potalioside B, luteolin 6-C-beta-D-glucopyranoside
      (isoorientin), apigenin 8-C-beta-D-glucopyranoside (vitexin), apigenin 6,8-di-C
      beta-D-glucopyranoside (vicenin-2), apigenin 6-C-alpha-L-arabinopyranosyl-8-C
      beta-D-glucopyranoside (isoschaftoside), apigenin 6-C-beta-D-glucopyranosyl-8-C
      beta-D-xylopyranoside, adenosine and l-tryptophan. Structure elucidations of
      these compounds were based on analyses of chemical and spectroscopic data,
      including 1D and 2D NMR. In addition, the isolated compounds were evaluated for
      their radical scavenging activities using both DPPH and ORAC assays.

PMID- 22152977
TI  - Lyngbyaureidamides A and B, two anabaenopeptins from the cultured freshwater
      cyanobacterium Lyngbya sp. (SAG 36.91).
AB  - Two anabaenopeptin-type peptides, lyngbyaureidamides A and B, together with two
      previously reported peptides lyngbyazothrins C and D, were isolated from the
      cultured freshwater cyanobacterium Lyngbya sp. (SAG 36.91). Their structures were
      determined by spectroscopic and chemical methods. Lyngbyazothrins C and D were
      also able to inhibit the 20S proteasome with IC(50) values of 7.1 MUM and 19.2
      MUM, respectively, while lyngbyaureidamides A and B were not active at 50 MUM.

PMID- 22152978
TI  - Effects of exercise training on pulmonary mechanics and functional status in
      patients with prolonged mechanical ventilation.
AB  - BACKGROUND: The functional status and outcomes in patients with prolonged
      mechanical ventilation (PMV) are often limited by poor endurance and pulmonary
      mechanics, which result from the primary diseases or prolonged time bedridden. We
      evaluate the impact of exercise training on pulmonary  mechanics, physical
      functional status, and hospitalization outcomes in PMV patients. METHODS: Twenty
      seven subjects with PMV in our respiratory care center (RCC) were divided
      randomly into an exercise training group (n = 12) and a control group (n = 15).
      The exercise program  comprised 10 sessions of exercise training. The measurement
      of pulmonary mechanics and physical functional status (Functional Independence
      Measurement and Barthel index) were performed pre-study and post-study. The
      hospitalization outcomes included: days of mechanical ventilation,
      hospitalization  days, and weaning and mortality rates during RCC stay. RESULTS:
      The training group had significant improvement in tidal volume (143.6 mL vs 192.5
      mL, P = .02) and rapid shallow breathing index after training (162.2 vs 110.6, P
      = .009). No significant change was found in the control  group except respiratory
      rate. Both groups had significant improvement in functional status during the
      study. However, the training group had greater changes in FIM score than the
      control group (44.6 vs 34.2, P = .024). The training group also had shorter RCC
      stay and higher weaning  and survival rates than the control group, although no
      statistical difference was found. CONCLUSIONS: Subjects with PMV in our RCC
      demonstrated significant improvement in pulmonary mechanics and functional status
      after exercise training. The application of exercise training may be helpful  for
      PMV patients to improve hospitalization outcomes.

PMID- 22152979
TI  - [Guidelines for Alzheimer's disease: the position of the French Neurological
      Society].

PMID- 22152980
TI  - A novel technique for femoral canal occlusion during cement pressurization in
      proximal femoral arthroplasty.
AB  - We describe a novel technique for occluding the femoral canal distal to the
      isthmus during proximal femoral arthroplasty. Synthetic bone models were reamed
      and sectioned to simulate loss of the proximal femur. Two experimental conditions
      were used. The first used no restrictor to act as a control. The second used
      calcium sulphate pellets impacted in distal femoral canal. A 100 * 12 mm Limb
      Preservation System stem (DePuy, Leeds, UK) was used in all experiments. We
      recorded cement pressure, leakage of cement, and penetration of cement into the
      femoral condyles. The calcium sulphate pellets prevented cement leakage, enabled
      higher cementing pressures, and prevented penetration of the cement into the
      femoral condyles. We would recommend this technique in cases where loss of
      proximal femoral bone loss requires the use of a cemented proximal femoral
      replacement.

PMID- 22152981
TI  - Morbidity in aged Finns: a systematic review.
AB  - AIM: The aim was to carry out a systematic review of original studies about
      morbidity in the aged in Finland. METHODS: Publications with data on morbidity in
      the aged (>=65 years) in peer-reviewed scientific journals in Finnish and English
      were systematically searched for in literature databases, websites of National
      Institute of Health and Welfare (NIHW), National Public Health Institute (NPHI),
      and Stakes and reference lists of retrieved articles. Publications from 1990
      onwards were included. RESULTS: The search produced 39 publications about
      morbidity in the aged in Finland fulfilling the inclusion criteria. The most
      common disease categories in the aged were cardiovascular diseases (CVDs),
      musculoskeletal disorders (MSDs), hypertension, orthostatic hypotension (OH),
      insomnia, diabetes, articular diseases, diseases causing cognitive decline, and
      depression. The prevalence of many of these diseases increased with age.
      CONCLUSIONS: The morbidity increases with aging, and even the oldest-old are not
      exceptionally healthy. Because of the increasing number of aged people, the
      absolute use of health and social services by this population sector will most
      probably increase in Finland and other developed countries.

PMID- 22152982
TI  - Cochlear implant rehabilitation for patients with vestibular schwannoma: report
      of two cases.
AB  - OBJECTIVE AND IMPORTANCE: The objective of this paper is to highlight two main
      points. The primary aim is to demonstrate that cochlear implants can function in
      the presence of retrocochlear pathology, even after stereotactic radiosurgery
      (SRS), and hence to introduce this as a management option in selected patients
      with retrocochlear pathology, such as Neurofibromatosis type II (NFII) patients.
      A secondary aim is to act as a caveat that computed tomography (CT) scanning
      alone may not be sufficient imaging in subjects undergoing cochlear implantation
      (CI). CLINICAL PRESENTATION: In this paper we report two patients who underwent
      cochlear implant despite the presence of a vestibular schwannoma (VS) on the same
      side. The first case is a 59-year-old male, diagnosed with VS after 9 months of
      good hearing with a cochlear implant. The second case is 26-year-old female known
      case of NFII, received a cochlear implant after controlling the tumor growth with
      a SRS. CONCLUSION: We show the consequences of missing important pre-implant
      pathology prior to CI in one case. In both cases, we add to the literature
      showing that cochlear implants can work well in the presence of VS, even in the
      presence of previous SRS. This adds significantly to the management options
      available to NFII patients, and the results seem to be better than those expected
      for auditory brainstem implant (ABI), and with a much simpler and safer
      intervention.

PMID- 22152983
TI  - Affective symptoms and intra-individual variability in the short-term course of
      cognitive functioning in bipolar disorder.
AB  - BACKGROUND: Few studies have examined the short-term course of cognitive
      impairments in bipolar disorder (BD). Key questions are whether trajectories in
      symptoms covary with cognitive function and whether BD is associated with
      increased intra-individual variability in cognitive abilities. METHOD: Forty-two
      out-patients with BD and 49 normal comparison (NC) subjects were administered a
      battery of neuropsychological tests at baseline, 6, 12 and 26 weeks, along with
      concurrent ratings of depressive and manic symptom severity. Mixed-effects
      regressions were used to model relationships between time, diagnosis and symptom
      severity on composite cognitive performance. Within-person variance in cognitive
      functioning across time was calculated for each subject. RESULTS: BD patients had
      significantly worse performance in cognitive ability across time points, but both
      groups showed significant improvement in cognitive performance over repeated
      assessments (consistent with expected practice effects). BD was associated with
      significantly greater intra-individual variability in cognitive ability than NCs;
      within-person variation was negatively related to baseline cognitive ability in
      BD but not NC subjects. Changes in affective symptoms over time did not predict
      changes in cognitive ability. CONCLUSIONS: Moderate changes in affective symptoms
      did not covary with cognitive ability in BD. The finding of elevated intra
      individual variability in BD may reduce capacity to estimate trajectories of
      cognitive ability in observational and treatment studies.

PMID- 22152984
TI  - [Unusual gallstone ileus].

PMID- 22152985
TI  - Physicochemical profile of macrolides and their comparison with small molecules.
AB  - Macrolides are stereospecific macrolactones of high molecular weights. Herein,
      600 mostly semisynthetic macrolides are compared with 50,000 small non-macrolide
      synthetic molecules in terms of measured physicochemical properties in order to
      assess the drug-likeness and developability chances of macrolides. The pre
      selected set of diverse macrolides is comprised mostly of derivatives of
      clarithromycin and azithromycin cores. Lipophilicity (CHI logD), affinity for
      immobilized artificial membranes (CHI IAM), human serum albumin (HSA) and
      alpha(1)-acid glycoprotein (AGP) plasma protein bindings (PPB), DMSO
      precipitative solubility as well as artificial membrane permeability (AMP) have
      been determined by high-throughput screening methods. It has been found that
      macrolides and small molecules have similar lipophilicity profiles, though
      macrolides show weaker PPB and have better solubility than small discovery
      molecules. However, macrolides are poorly permeable and have high affinity for
      immobilized artificial membranes signifying their strong interaction with
      biological phospholipids. In order to retain the drug-like profile, the design of
      novel macrolide molecules should be focused on optimisation of macrolide cores,
      that is macrolactone moiety with sugars and other small substituents avoiding
      large substituents and flexible linkers such as in conjugate derivatives.

PMID- 22152986
TI  - N-Aryl-2-phenyl-2,3-dihydro-imidazo[1,2-b]pyrazole-1-carboxamides 7-substituted
      strongly inhibiting both fMLP-OMe- and IL-8-induced human neutrophil chemotaxis.
AB  - Anomalous activation of neutrophil recruitment is one of the causes of many
      inflammatory diseases. The chemoattractants N-formyl-methionyl-leucyl
      phenylalanine (fMLP), and interleukine 8 (IL8) play a pivotal role in neutrophil
      chemotaxis regulation in the latter and early stages, respectively, probably by
      two independent mechanisms. We reported here synthesis and biological evaluation
      of new N-aryl-2-phenyl-2,3-dihydro-imidazo[1,2-b]pyrazole-1-carboxamides 7
      substituted which were designed as possible multi-target antiinflammatory agents.
      Many of the title compounds showed a good inhibition, in the nano molar range, of
      human neutrophil chemotaxis selectively acting toward fMLP-OMe (methylester of
      fMLP) or IL8 stimulus; whereas, two compounds showed an interesting dual activity
      inhibiting both fMLP-OMe and IL8-induced chemotaxis at nano molar concentration.

PMID- 22152987
TI  - Aetiology of acute gastroenteritis in adults requiring hospitalization in The
      Netherlands.
AB  - SUMMARY Infectious gastroenteritis causes a considerable burden of disease
      worldwide. Effective control should be targeted at diseases with the highest
      burden and costs. Therefore, an accurate understanding of the relative importance
      of the different microorganisms is needed. The objective of this study was to
      determine the incidence and aetiology of gastroenteritis in adults requiring
      hospital admission in The Netherlands. Five hospitals enrolled patients admitted
      with gastroenteritis for about 1 year during the period May 2008 to November
      2009. Participants completed questionnaires and provided a faecal sample. The
      hospital completed a clinical questionnaire. In total, 44 adults hospitalized for
      gastroenteritis were included in the study. The cases had serious symptoms, with
      31% subsequently developing kidney failure. One or more pathogens were found in
      59% of cases. Overall, rotavirus (22%) was the most common infection. Co
      infections were observed relatively often (22%). This study emphasizes that
      rotavirus can also cause serious illness in adults.

PMID- 22152988
TI  - Carotenoid exposure of Caco-2 intestinal epithelial cells did not affect selected
      inflammatory markers but altered their proteomic response.
AB  - Carotenoid consumption has been linked to a number of beneficial health effects,
      including the reduction of chronic diseases such as cancer and cardiovascular
      complications. However, no data are available on their action on the intestinal
      epithelium, being exposed to the highest concentrations of carotenoids in the
      human body, and where they could act preventively on intestinal inflammatory
      diseases such as Crohn's disease and ulcerative colitis. The objective of the
      present study was to investigate whether lycopene and beta-carotene in micelles
      (M), at concentrations that could be reached via the diet (10-25 MUg/ml) could
      aid in the reduction of TNF-alpha plus IL-1beta-induced inflammation of Caco-2
      human epithelial cells. The impact on biomarkers of inflammation, including IL-8,
      NO and cyclo-oxygenase-2 (through PGE-2alpha), and the NF-kappaB and mitogen
      activated protein kinase (MAPK) pathways of intracellular signalling cascades
      were evaluated compared with controls (empty M). Furthermore, proteomic analyses
      were conducted from total cellular protein extracts. The results revealed that
      isolated carotenoids had no statistical significant anti-inflammatory effect on
      the biomarkers observed, or on the regulation of NF-kappaB and MAPK.
      Nevertheless, analyses of the proteome suggested that fifteen proteins were
      significantly (P < 0.05, expression ratio >1.3) differentially regulated
      following beta-carotene exposure, participating mostly in metabolic activities
      including antioxidant mechanisms, such as glutathione S-transferase A1. Only one
      protein was differentially regulated by lycopene (profilin-1). To our knowledge,
      this is the first attempt to investigate pathways involved in the action of
      carotenoids on the intestinal epithelium.

PMID- 22152989
TI  - Pushing the detection limits: the evanescent field in surface plasmon resonance
      and analyte-induced folding observation of long human telomeric repeats.
AB  - Conventional analysis of molecular interactions by surface plasmon resonance is
      achieved by the observation of optical density changes due to analyte binding to
      the ligand on the surface. Low molecular weight interaction partners are normally
      not detected. However, if a macromolecule such as DNA can extend beyond the
      evanescent field and analyte interaction results in a large-scale contraction,
      then the refractive index changes due to the increasing amount of macromolecules
      close to the surface. In our proof-of-principle experiment we could observe the
      direct folding of long, human telomeric repeats induced by the small analyte
      potassium using surface plasmon resonance spectroscopy. This work demonstrates
      the feasibility of new evanescent field-based biosensors that can specifically
      observe small molecule interactions.

PMID- 22152990
TI  - Development of a one-step immunochromatographic strip test using gold
      nanoparticles for the rapid detection of Salmonella typhi in human serum.
AB  - An immunochromatographic strip test using gold nanoparticles was developed for
      the rapid detection of Salmonella typhi (S. typhi) in human serum. The strip test
      based on the principle of sandwich immunoassay by the specific binding of
      antigens from S. typhi O901 and antibody of S. typhi O901 on a nitrocellulose
      membrane. Antibody-gold nanoparticle conjugate was used as the label and was
      coated onto a glass fiber membrane, which was used as a conjugate pad. To create
      a test and control zone, antibody of S. typhi O901 and an anti-IgG were dotted on
      the nitrocellulose membrane, respectively. Positive samples were displayed as red
      dots at the test and control zones of the nitrocellulose membrane, while negative
      samples resulted in a red dot only in the control zone. The limit of detection
      (LOD) was found to be 1.14*10(5) cfu mL(-1), which could be visually detected by
      the naked eye within 15 min. This strip test provided a lower detection limit and
      analysis time than a dot blot immunoassay (8.88*10(6) cfu mL(-1) for LOD and 110
      min for reaction time). In addition, our immunochromatographic strip test was
      employed to detect S. typhi in human serum effectively, with high accuracy. This
      strip test offers great promise for a rapid, simple and low-cost analysis of S.
      typhi.

PMID- 22152991
TI  - Ca2+ ion transport through channels formed by alpha-hemolysin analyzed using a
      microwell array on a Si substrate.
AB  - For the functional analysis of ion channel activity, an artificial lipid bilayer
      suspended over microwells was formed that ruptured giant unilamellar vesicles on
      a Si substrate. Ca(2+) ion indicators (fluo-4) were confined in the microwells by
      sealing the microwells with a lipid bilayer. An overhang formed at the microwells
      prevented the lipid membrane from falling into them and allowed the stable
      confinement of the fluorescent probes. The transport of Ca(2+) ions through the
      channels formed by alpha-hemolysin inserted in a lipid membrane was analyzed by
      employing the fluorescence intensity change of fluo-4 in the microwells. The
      microwell volume was very small (1-100 fl), so a highly sensitive monitor could
      be realized. The detection limit is several tens of ions/s/MUm(2), and this is
      much smaller than the ion current in a standard electrophysiological measurement.
      Smaller microwells will make it possible to mimic a local ion concentration
      change in the cells, although the signal to noise ratio must be further improved
      for the functional analysis of a single channel. We demonstrated that a microwell
      array with confined fluorescent probes sealed by a lipid bilayer could constitute
      a basic component of a highly sensitive biosensor array that works with
      functional membrane proteins. This array will allow us to realize high throughput
      and parallel testing devices.

PMID- 22152992
TI  - Sensitive detection of histamine using fluorescently labeled oxido-reductases.
AB  - A detection scheme is described by which the histamine contents of biological
      samples can be established. The scheme is based on the use of methylamine
      dehydrogenase (MADH) which converts primary amines into the corresponding
      aldehydes and ammonia. The generated reducing equivalents are subsequently
      transferred to the physiological partner of MADH, amicyanin, which thereby is
      converted from the oxidized blue-colored form into the reduced colorless form.
      The change in absorption is detected by monitoring the fluorescence of a
      covalently attached Cy5 dye label whose fluorescence is (partly) quenched by
      Forster resonance energy transfer (FRET) to the Cu-site of the amicyanin. The
      quenching efficiency and, thereby, the label fluorescence, depends on the
      oxidation state of the amicyanin. When adding histamine to the assay mixture the
      proportionality between the substrate concentration and the observed rate of the
      fluorescence increase has enabled this assay as a sensor method with high
      sensitivity. The MADH and amicyanin composition can be tuned so that the sensor
      can be adapted over a broad range of histamine concentrations (13 nM-225 MUM).
      The lowest concentration detected so far is 13 nM of histamine. The sensor
      retained its linearity up to 225 MUM with a coefficient of variation of 11% for
      10 measurements of 100nM histamine in a 100 MUL sample volume. The use of a label
      fluorescing around 660 nm helps circumventing the interference from background
      fluorescence in biological samples. The sensor has been tested to detect
      histamine in biological fluids such as fish extracts and blood serum.

PMID- 22152993
TI  - Dietary habits of partly breast-fed and completely weaned infants at 9 months of
      age.
AB  - OBJECTIVE: To test whether there are differences in diet diversity between
      children still being partly breast-fed at 9 months and those completely weaned at
      the same age. DESIGN: Cross-sectional study. SETTING: Cross-sectional study (SKOT
      cohort) in the area of Copenhagen, Denmark. SUBJECTS: Healthy term infants (n
      312) at 9 months of age (mean 9.1 (SD 0.3) months). RESULTS: The infants partly
      breast-fed (n 168) at 9 months had significantly lower body weight (P < 0.0001),
      were significantly shorter (P = 0.0022) and were introduced to complementary
      foods significantly later (P < 0.0001) than completely weaned infants (n 141) of
      similar age. Furthermore, they had lower intake of energy, both in absolute
      amount (P < 0.0001) and per kilogram of body weight (P = 0.049). Significantly
      lower intakes of most energy-yielding nutrients, in absolute amounts and as
      energy percentages, were seen for the partly breast-fed compared with the
      completely weaned infants. These differences appear to be caused primarily by
      differences in the type and amount of milk consumed, as the energy derived from
      sources other than milk was similar except for fatty spread and vegetables as a
      side dish. Only small differences were found for absolute intakes of foods
      between feeding groups, although fatty spread had significantly higher intake
      rates and consumption (P = 0.031) among partly breast-fed compared with
      completely weaned infants. CONCLUSIONS: At 9 months the infants partly breast-fed
      did not eat a less diversified diet compared with those completely weaned at the
      same age. Despite later introduction to complementary foods compared with the
      completely weaned, their intake of foods was similar and no delay in their
      progression towards the family foods was noted.

PMID- 22152994
TI  - Modulation of autoimmune demyelination by laquinimod via induction of brain
      derived neurotrophic factor.
AB  - Laquinimod is a promising, orally available compound that has been successfully
      evaluated in placebo-controlled phase II/III studies of relapsing-remitting
      multiple sclerosis (MS). Studies are ongoing to further define laquinimod's
      modulatory mechanisms. Analyses in the animal model of experimental autoimmune
      encephalomyelitis (EAE) demonstrate that laquinimod reduces infiltration of
      leukocytes into the central nervous system, induces a Th1 to Th2/3 shift, and
      suppresses Th17 responses. To evaluate the potential neuroprotective capacity of
      laquinimod via modulation of brain-derived neurotrophic factor (BDNF), we
      analyzed the expression of BDNF in blood samples from 203 MS patients treated
      with laquinimod. Furthermore, we investigated the effect of laquinimod in EAE
      using a conditional BDNF knockout strain lacking BDNF expression in myeloid cells
      and T cells (LLF mice). Treatment with laquinimod resulted in a significant and
      persistent increase in BDNF serum levels of MS patients when compared to baseline
      and placebo-treated patients. LLF mice treated with laquinimod display a more
      severe EAE disease course in comparison to wild-type mice. Furthermore,
      laquinimod-treated wild-type monocytes secreted an anti-inflammatory cytokine
      pattern in comparison to untreated wild-type monocytes and treated LLF monocytes.
      Adoptive transfer of laquinimod stimulated monocytes into mice with EAE
      ameliorated the disease course. Consistent with immunomodulatory properties,
      laquinimod skewed monocytes toward a regulatory phenotype and also acted via
      modulation of BDNF, which may contribute to neuroprotection in MS patients.

PMID- 22152995
TI  - The BTB/POZ zinc finger protein Broad-Z3 promotes dendritic outgrowth during
      metamorphic remodeling of the peripheral stretch receptor dbd.
AB  - BACKGROUND: Various members of the family of BTB/POZ zinc-finger transcription
      factors influence patterns of dendritic branching. One such member, Broad, is
      notable because its BrZ3 isoform is widely expressed in Drosophila in immature
      neurons around the time of arbor outgrowth. We used the metamorphic remodeling of
      an identified sensory neuron, the dorsal bipolar dendrite sensory neuron (dbd),
      to examine the effects of BrZ3 expression on the extent and pattern of dendrite
      growth during metamorphosis. RESULTS: Using live imaging of dbd in Drosophila
      pupae, we followed its normal development during metamorphosis and the effect of
      ectopic expression of BrZ3 on this development. After migration of its cell body,
      dbd extends a growth-cone that grows between two muscle bands followed by
      branching and turning back on itself to form a compact dendritic bundle. The
      ectopic expression of the BrZ3 isoform, using the GAL4/UAS system, caused dbd's
      dendritic tree to transform from its normal, compact, fasciculated form into a
      comb-like arbor that spread over on the body wall. Time-lapse analysis revealed
      that the expression of BrZ3 caused the premature extension of the primary
      dendrite onto immature myoblasts, ectopic growth past the muscle target region,
      and subsequent elaboration onto the epidermis. To control the timing of
      expression of BrZ3, we used a temperature-sensitive GAL80 mutant. When BrZ3
      expression was delayed until after the extension of the primary dendrite, then a
      normal arbor was formed. By contrast, when BrZ3 expression was confined to only
      the early outgrowth phase, then ectopic arbors were subsequently formed and
      maintained on the epidermis despite the subsequent absence of BrZ3. CONCLUSIONS:
      The adult arbor of dbd is a highly branched arbor whose branches self-fasciculate
      to form a compact dendritic bundle. The ectopic expression of BrZ3 in this cell
      causes a premature extension of its growth-cone, resulting in dendrites that
      extend beyond their normal muscle substrate and onto the epidermis, where they
      form a comb-shaped, ectopic arbor. Our quantitative data suggest that new ectopic
      arbor represents an 'unpacking' of the normally fasciculated arbor onto the
      epidermis. These data suggest that the nature of their local environment can
      change dendrite behavior from self-adhesion to self-avoidance.

PMID- 22152996
TI  - [Out-of-hospital assessment of elderly patients' preference for ICU care].
AB  - OBJECTIVE: To estimate the adequacy between elderly patients' preference for ICU
      care when treated for a life-threatening pathology, and the strategy proposed by
      the medical team on scene. STUDY DESIGN: Prospective, observational study.
      PATIENTS AND METHODS: All patients older than 80 treated out-of-hospital for a
      life threatening pathology were included, except in case of language barrier, or
      when patients were unable to answer and absence of next-of-kin. The results of
      the questionnaire on quality of life and patients' preference concerning ICU care
      were compared to the responses provided blindly by the medical team. RESULTS:
      Fifty-five patients were included. Quality of life as expressed by the patients
      was 7 (5-10) and by the physician 7 (6-8) (P=0.69). Thirty-six patients (65%)
      expressed the wish to be resuscitated, while ICU admission would have been
      proposed for 44 patients (80%) by the doctors (P=0.01). Among the 14 patients
      reluctant to ICU admission, 11 would have been proposed for ICU admission. In
      multivariate analysis, age (OR: 1.55 [1.04-2.32], P=0.03) and history of
      neurological pathology (OR: 11,91 [5.68->100], P=0.04) were associated with such
      an inadequacy. CONCLUSION: The inadequacy between elderly patients' preferences
      and doctors' opinion concerning ICU cares is frequent. The present results
      support a more systematic collection of patients' preferences when treated on
      scene for a life-threatening pathology.

PMID- 22152997
TI  - [A protocol for the cessation of sedation in brain-injured patients].
AB  - OBJECTIVES: The cessation of sedation in brain-injured patients may result in
      severe agitation and/or acute withdrawal syndrome related to the prolonged
      administration of large doses of benzodiazepines and/or opioids. The aim of the
      present study was to assess the clinical efficacy of a written protocol to
      withdraw sedation for these patients. STUDY DESIGN: Observational prospective
      study. PATIENTS AND METHODS: After approval by the Institutional Review Board, 40
      severely brain-injured patients were included. They had received continuous
      administration of midazolam and sufentanil or fentanyl for median 15 days. On
      cessation of midazolam infusion, patients were given clorazepate for 3 days. On
      cessation of opioid infusion and clorazepate, clinical data were collected for 48
      hours: heart rate, systolic blood pressure, respiratory rate, agitation, and
      pupil diameter. If an opioid withdrawal syndrome occurred, patients received a 48
      hour continuous infusion of buprenorphine. RESULTS: Of 40 patients, there were 10
      who did not require buprenorphine. An agitation occurred 5 hours (1-21) after
      cessation of opioid, associated with tachycardia, arterial hypertension, and
      tachypnea. After 6 hours buprenorphine treatment, these parameters were
      normalized. No patient needed the reintroduction of the initial sedation.
      CONCLUSION: The cessation of sedation in severely brain-injured patients can be
      successfully managed with the use of clorazepate, associated with buprenorphine
      in the presence of agitation.

PMID- 22152998
TI  - [Stability and compatibility of acetaminophen, ketoprofen and amoxicillin in a
      fail-safe intravenous administration set].
AB  - OBJECTIVES: Intravenous infusion takes an important place in the current therapy
      in hospitals and pharmaceutical firms keep improving their infusion medical
      devices, particularly with the development of an intravenous administration set
      with an automatic infusion stop. The aim of our study consists in an evaluation
      of the stability of acetaminophen, ketoprofen and amoxicillin during infusion and
      stasis of drugs for several hours in the dropper chamber and in the tube of this
      device. STUDY DESIGN: Analytical study. MATERIALS AND METHODS: Ten milligram per
      millilitre acetaminophen (acetaminophen 1 and acetaminophen 2), 1 mg/mL
      ketoprofen and 20 mg/mL amoxicillin were prepared and infused individually and
      successively with the intravenous administration set under ambient light and
      temperature. Collected samples of each drug during the infusion and after 24
      hours of stasis in the medical device were monitored by a visual inspection, pH
      and osmolality assessment and chromatographic analysis of each drug with a
      validated stability-indicating method. RESULTS: Repeated individual perfusions of
      10 mg/mL acetaminophen 1 or 1 mg/mL ketoprofen are possible through a fail-safe
      intravenous administration set, while repeated individual amoxicillin infusions
      are not because of the unstability of this drug. There is also no problem to
      infuse successively acetaminophen and ketoprofen through this medical device
      because these drugs are stable. However, we underlined an incompatibility between
      acetaminophen 2 and ketoprofen, which advises against the use of intravenous
      administration set for successive infusions of these two drugs. CONCLUSION:
      Despite the technical innovation of a fail-safe intravenous administration set,
      we have to stay aware of mixture consequences in intravenous infusion field.

PMID- 22152999
TI  - High-frequency oscillatory ventilation for rescue from refractory hypoxemia in a
      patient with transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury is a serious complication of blood
      transfusions. Herein is a report on a 32-year-old woman who developed diffuse
      pulmonary infiltrates and acute respiratory compromise after blood transfusion.
      Non-cardiogenic pulmonary edema was diagnosed based  on data calculated by the
      hemodynamic monitoring system, but severe hypoxemia persisted despite
      conventional pressure-control ventilation with 100% oxygen, low tidal volume, and
      high PEEP. The refractory hypoxemia was improved by high-frequency oscillatory
      ventilation. This experience suggests  that high-frequency oscillatory
      ventilation may be beneficial for patients with transfusion-related acute lung
      injury and severe refractory hypoxemia.

PMID- 22153000
TI  - Trends and risk factors for HIV infection among young pregnant women in rural
      India.
AB  - OBJECTIVES: To study the trends of the HIV epidemic and risk factors associated
      with HIV in a rural area of India. We utilized HIV prevalence among young
      pregnant women as an indicator of population trends in HIV infection. METHODS:
      This was an observational study of pregnant women aged less than 25 years who
      were counseled and tested for HIV infection in a rural hospital between August
      2007 and June 2011. Information on age, education, occupation, and community were
      collected prospectively from all of the women. RESULTS: The HIV prevalence in
      young pregnant women decreased from 1.22% in 2007 to 0.35% in 2011. Comparing the
      periods 2007-2009 and 2010-2011, a reduction in HIV prevalence was seen in all
      subgroups except in women from forward castes. Women whose job was not related to
      agriculture and women who had only completed primary education were more likely
      to be HIV-infected. CONCLUSIONS: These results indirectly indicate that the
      incidence of HIV infection is decreasing in this rural setting. However, an
      increase in the HIV prevalence in women from forward castes was observed. In
      rural areas, HIV testing of pregnant women who have only completed primary
      education or who are working in a field not related to agriculture should be
      encouraged, because of their higher risk of HIV infection.

PMID- 22153001
TI  - Randomized controlled study of fractional doses of inactivated poliovirus vaccine
      administered intradermally with a needle in the Philippines.
AB  - OBJECTIVE: Comparison of a fractional inactivated poliovirus vaccine (IPV) dose
      administered intradermally (ID) to a full dose administered intramuscularly (IM).
      METHODS: Healthy Filipino infants were randomized to receive IPV as either a
      fractional (1/5(th)) dose ID by needle injection or a full dose IM at 6, 10, and
      14 weeks and a booster at 15-18 months of age. Pre- and post-vaccination anti
      polio 1, 2, and 3 titers were estimated. Adverse events were monitored throughout
      the study. RESULTS: Following primary series vaccination, anti-polio 1, 2, and 3
      titers were >=8 (1/dil) in 99-100% of participants, and the ID route was non
      inferior to the IM route. Depending on the study group, antibody persistence was
      detected in 83-100% of participants, and the booster dose resulted in a strong
      anamnestic response in all groups. The incidence of adverse events in each group
      was similar, except for injection-site erythema (higher in the ID group).
      CONCLUSIONS: Primary series and booster vaccination of a fractional IPV dose
      administered by the ID route was highly immunogenic and well tolerated. These
      data confirm the medical validity of using fractional ID doses of IPV. The
      programmatic feasibility of implementing affordable mass vaccination programs
      based on this delivery mode has yet to be established.

PMID- 22153002
TI  - Postprandial hypertriglyceridemia predicts improvement in insulin resistance in
      obese patients after bariatric surgery.
AB  - BACKGROUND: Morbidly obese patients have associated diseases, such as diabetes,
      hypertension, hyperlipidemia, and cardiovascular disease. Bariatric surgery
      improves these obesity-related co-morbidities, including insulin resistance.
      Evidence has shown that patients with morbid obesity have postprandial
      hypertriglyceridemia (HTG) and that this type of HTG is related to the degree of
      insulin resistance. Also, bariatric surgery produces a dramatic reduction in
      triglyceride levels. However, it is unknown whether patients with postprandial
      HTG have a different clinical evolution after bariatric surgery. The setting of
      our study was a university hospital. METHODS: We studied 57 morbidly obese
      patients who had mild or severe postprandial HTG after fat overload (<30 mg/dL or
      >90 mg/dL increase in triglycerides, respectively). All the patients underwent
      bariatric surgery. After surgery, the anthropometric and biochemical variables
      and the Homeostasis Model Assessment of Insulin Resistance were measured for 1
      year at 0, 15, 30, 45, 90, 180, and 365 days after surgery. RESULTS: The patients
      with more severe postprandial HTG had a greater percentage of change in the
      Homeostasis Model Assessment of Insulin Resistance at 30, 90, and 180 days after
      surgery than the patients with less severe postprandial HTG. Multiple regression
      analysis showed that the postprandial triglyceride levels predict the variation
      in the Homeostasis Model Assessment of Insulin Resistance index, more so than did
      traditional variables, such as anthropometric, inflammatory, or hormonal data.
      CONCLUSION: The postprandial HTG level might be the best predictor of improved
      insulin resistance in morbidly obese patients after bariatric surgery.

PMID- 22153003
TI  - Port fixation during gastric banding: 4-year outcome using a synthetic mesh.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding surgery is one of the most
      popular procedures for patients with morbid obesity. Although it is one of the
      least invasive surgical treatments for obesity, the most common reasons for
      reoperation are complications arising from the subcutaneous reservoir (port) used
      to adjust the band. Mesh fixation of the port, in which the port is sutured to a
      piece of mesh and then placed without anchoring sutures onto the fascia is a
      method of securing the port. The purpose of the present study was to review the
      experience of a single surgeon (S.B.) with mesh fixation in >500 patients during
      a 4-year period and to assess the safety and efficacy of this technique in
      private practice in United States. METHODS: A total of 564 patients underwent
      laparoscopic gastric banding during a 4-year period from January 2007 to January
      2011. During these operations, the subcutaneous port was affixed to the fascia by
      suturing the port to a small piece of polypropylene mesh and then placing the
      port onto the fascia without any additional anchoring sutures or staples.
      RESULTS: Of 564 patients, only 2 required reoperation to reposition the
      subcutaneous port, for a .3% port flip rate. We also report the findings during
      elective reoperation for plastic surgery or revision surgery. CONCLUSION: Mesh
      fixation of the subcutaneous port is simple, inexpensive, and highly effective
      and has an extremely low complication rate.

PMID- 22153004
TI  - [The short-term prognosis for hospitalized acute myocardial infarction patients:
      the impact of complication by community-acquired pneumonia].
AB  - OBJECTIVE: To analyze the correlation between the complication by community
      acquired pneumonia (CAP) and the short-term prognosis in hospitalized acute
      myocardial infarction (AMI) patients. METHODS: Five thousand five hundred and
      twenty-four AMI patients hospitalized in the PLA General Hospital from January
      1993 to December 2009 were enrolled for clinical data, incidence of complications
      and 30-day mortality. The data from patients with and without CAP complications
      were compared. Multivariate logistic regression analysis was employed to assess
      the impact of CAP on the short-term prognosis of these patients. RESULTS: In all
      5 524 AMI patients studied, 477 cases of CAP was found (8.6%) . In comparison
      with those without CAP complication, these patients had higher age (74.3 +/- 6.5
      vs. 67.8 +/- 4.5).  The incidence of comorbidities [including old myocardial
      infarction (20.8% vs. 11.5%), hypertension (54.3% vs. 48.9%), diabetic mellitus
      (32.7% vs. 22.6%), cerebral-vascular disease (8.2% vs. 3.5%), chronic renal
      dysfunction (10.5% vs. 3.0%)], and complications [including arrhythmia (8.8% vs.
      4.6%), gastrointestinal bleeding (5.0% vs. 0.8%) and shock (8.6% vs. 3.1%)] were
      all significantly higher, and hyperlipidemia (18.9% vs. 30.6%) was significantly
      lower (P < 0.05 or P < 0.01)  in CAP complicated patients. The 30-day mortality
      was also significantly higher (32.1% vs. 9.7%, P < 0.01). Multivariate logistic
      regression analysis identified CAP and chronic renal dysfunction as an
      independent predictor of short-term mortality [odds ratio (OR) of CAP 3.693, 95%
      confidence interval (95%CI) 2.340 ~ 5.829, P < 0.01; OR of chronic renal
      dysfunction 12.608, 95%CI 4.448 ~ 35.739, P < 0.01]. CONCLUSIONS: The incidence
      of CAP complication was higher in AMI patients with higher age.CAP complicated
      patients were more likely to develop comorbidities/complications, and had higher
      short-term mortality. CAP was an independent risk factor of short-term mortality.

PMID- 22153005
TI  - [Coronary artery bypass grafting for elderly with unprotected left main coronary
      artery disease: a clinical analysis].
AB  - OBJECTIVE: To study the correlation between the clinical features and the
      prognosis in elderly patients with unprotected left main coronary artery disease
      (ULMCA) after coronary artery bypass grafting (CABG). METHODS: The clinical
      parameters and prognosis data from 176 patients received CABG for ULM were
      retrospectively analyzed for comparison of elderly (age>=65) and against non
      elderly (age < 65). RESULTS: The elderly patients were found to have
      significantly higher level of blood high density lipoprotein cholesterin (HDL-C,
      mmol/L: 28.36 +/- 17.20 vs. 13.68 +/- 7.78, P < 0.01), lower level of blood low
      density lipoprotein cholesterin (LDL-C, mmol/L: 1.21 +/- 0.77 vs. 2.48 +/- 1.27,
      P < 0.01) and higher level of coronary stenosis [(94.56 +/- 8.01)% vs. (87.96 +/-
      11.10)%, P < 0.01]. The incidence of multi-vessel disease (75.9% vs. 58.1%, P <
      0.05) and chronic total occlusion (55.4% vs. 29.0%, P < 0.05) were both
      significantly higher in the elderly. No significant difference was found between
      the two groups in major adverse cardiac and cerebral events (MACCE), cerebral
      infarction, myocardial infarction, cardiac mortality, and total mortality (16.9%
      vs 17.2%, 3.6% vs 3.2%, 3.6% vs 5.4%, 6.0% vs 9.7%, and 12.0% vs 8.6%, all P >
      0.05). CONCLUSION: In the elderly ULMCA patients the coronary lesions are more
      severe, but CABG is still a safe and efficient therapy for these patients.

PMID- 22153006
TI  - [Intensive insulin treatment protected the cardiac myocytes against apoptosis in
      severely scalded rats].
AB  - OBJECTIVE: To investigate the effect of intensive insulin treatment, in the
      protection of myocardiocytes against apoptosis in severely scalded rats and its
      underlying mechanism. METHODS: Eighteen Sprague-Dawley (SD) rats were randomly
      divided into three groups (6/each) to receive: sham surgery, burn damage (on the
      back of the animals, degreeIII, to 30% of total body surface area), and burn
      damage+intensive insulin treatment. Tissue samples were collected from the left
      ventricle 6 hours after infliction of the burn damage for the examination of
      myocardial cell apoptosis [by terminal-deoxynucleotidyl transferase mediated nick
      end labeling (TUNEL) staining] and the expression of apoptosis-related molecules
      caspase-3, Bax, and Bcl-2 (by immuno-histochemistry and Western blotting).
      RESULTS: In comparison with the animals in sham treated group, the myocardiocyte
      apoptosis rate in animals in burn damage only group increased significantly
      [(13.1 +/- 3.4)% vs. (0.6 +/- 0.4)%, P < 0.01]. The expression of caspase-3 and
      Bax both significantly increased while the level of Bcl-2 expression
      significantly decreased (immuno-histochemistry caspase-3: 13.72 +/- 4.13 vs. 1.36
      +/- 0.95, Bax: 29.64 +/- 5.42 vs. 2.24 +/- 1.04, Bcl-2: 3.39 +/- 1.52 vs. 8.01 +/
      2.56; Western blotting caspase-3: 5.72 +/- 2.13 vs. 1, Bax: 4.64 +/- 1.42 vs. 1,
      Bcl-2: 0.69 +/- 0.42 vs. 1, all P < 0.01). The animals received intensive insulin
      treatment showed significantly less myocardiocyte apoptosis [(6.7 +/- 1.8)% vs.
      (13.1 +/- 3.4)%, P < 0.01], significantly lower expression in caspase-3, Bax, and
      significantly higher level of Bcl-2 expression as compared to the animals in burn
      damage only group (immuno-histochemistry caspase-3: 8.88 +/- 3.36 vs. 13.72 +/-
      4.13, Bax: 14.43 +/- 3.69 vs. 29.64 +/- 5.42, Bcl-2: 8.61 +/- 3.72 vs. 3.39 +/-
      1.52; Western blotting caspase-3: 2.18 +/- 0.86 vs. 5.72 +/- 2.13, Bax: 2.87 +/-
      1.35 vs. 4.64 +/- 1.42, Bcl-2: 3.57 +/- 1.70 vs. 0.69 +/- 0.42, P < 0.05 or P <
      0.01). CONCLUSION: Intensive insulin therapy may protect myocardiocytes against
      apoptosis in severely burned animals through the regulation of the expression of
      apoptosis-related molecules caspase-3, Bax and Bcl-2.

PMID- 22153007
TI  - [Circulating microRNA-92a in patients with ST-segment elevation myocardial
      infarction].
AB  - OBJECTIVE: To examine the expression of circulating microRNA-92a (miR-92a) in
      patients with ST-segment elevation myocardial infarction (STEMI), and the impact
      of percutaneous coronary intervention (PCI) on such expression. METHODS: The
      level of circulating miR-92a was measured in three groups of patients: 58 STEMI
      patients received PCI, 24 STEMI patients received no PCI, and 116 patients with
      stable angina pectoris (SAP) without PCI. RESULTS: On the day next to admission,
      STEMI patients received no PCI were found to have higher level of circulating miR
      92a as compared to SAP patients without PCI (0.2869 +/- 0.8167 vs. -0.0555 +/-
      0.9855, F = 2.438, P = 0.121). Twenty-four hours after the PCI, the level of
      circulating miR-92a in STEMI patients received the procedure was lower than those
      without it (-0.0324 +/- 0.9563 vs. 0.2869 +/- 0.8167, F = 2.054, P = 0.156). The
      SAP patients (without PCI) had higher survival rate as compared to the STEMI
      patients without PCI (100.0% vs. 75.0% P = 0.001), and the survival rate in STEMI
      patients received PCI was higher than those without it (89.7% vs. 75.0%, P =
      0.088). CONCLUSIONS: In STEMI patients, the expression of circulating miR-92a is
      up-regulated. PCI therapy may suppress such up-regulation. Survival rate is
      higher in patients showing down-regulation of miR-92a. Our data suggest that miR
      92a might have potential for diagnosis and therapeutic application in the
      prevention and treatment of STEMI.

PMID- 22153008
TI  - [The limitation of MB isoenzyme of creatine kinase mass in assess myocardial
      injury with muscular disease].
AB  - OBJECTIVE: To examine the changes in serum MB isoenzyme of creatine kinase mass
      (CK-MB mass), cardiac troponin I (cTnI), and myoglobulin (Mb) in children with
      myocarditis and muscular disease in order to evaluate the significance of index
      CK-MB mass for the diagnosis of myocardium injury in these diseases. METHODS:
      Blood samples were collected from 40 children with myocarditis, 38 children with
      muscular diseases, and 10 healthy children, for the measurement of creatine
      kinase (CK), CK-MB activity, CK-MB mass, cTnI, and Mb. Myocarditis patients also
      received electrocardiogram and pulse Doppler electrocardiogram examination while
      muscular diseases patients were subjected to electro-myographic examination,
      inherit-metabolic diseases screening and related gene analysis. The data were
      analyzed for differences between groups, and differences between values before
      and after the treatment. RESULTS: In comparison with healthy controls [CK (U/L):
      95.0 +/- 27.0, CK-MB activity (U/L): 22.6 +/- 1.3, CK-MB mass (MUg/L): 2.4 +/-
      0.3, cTnI (MUg/L): 0.012 +/- 0.001], the patients with myocarditis had
      significantly (all P < 0.01) higher mean values in CK (1033.0 +/- 408.0), CK-MB
      activity (101.2 +/- 31.5), CK-MB mass (38.2 +/- 13.2) and cTnI (5.544 +/- 1.554)
      before the treatment. After 2 weeks of treatment these indexes returned to the
      level of controls, with cTnI responded the last (CK: 59.3 +/- 25.1, CK-MB
      activity: 24.6 +/- 13.2, CK-MB mass: 3.3 +/- 2.9, cTnI: 0.125 +/- 0.128). One
      week after treatment, the incidences of CK and CK-MB mass elevation were
      significantly lower than the values before the treatment [CK: 5.9% (1/17) vs.
      56.4% (22/39); CK-MB mass: 8.3% (1/12) vs. 61.1% (22/36), both P < 0.01], with
      the change in CK-MB mass appeared significantly earlier than cTnI [8.3% (1/12)
      vs. 73.7% (14/19), P < 0.05]. The patients with muscular disease also had
      significantly elevated mean value in CK (10193.0 +/- 1447.0), CK-MB activity
      (311.7 +/- 44.4), and CK-MB mass (229.2 +/- 47.9) in comparison with healthy
      controls before the treatment (all P < 0.01). But their cTnI (0.021 +/- 0.002)
      was not significantly different from the control at this time. Two weeks after
      treatment, the elevated indexes were still significantly higher than the control
      (CK: 5735.6 +/- 6187.8, CK-MB activity: 170.7 +/- 143.0, CK-MB mass: 207.4 +/-
      136.6), while the level of cTnI (0.230 +/- 0.150) remained at the level of the
      control group. The incidence of index elevation was not significantly different
      from the values before the treatment for all the indexes tested [CK: 85.7% (6/7)
      vs. 97.4% (37/38); CK-MB activity: 85.7% (6/7) vs. 97.4% (37/38); CK-MB mass:
      100.0% (2/2) vs. 94.1% (32/34); cTnI: 0(0/1) vs. 6.4% (2/31), all P > 0.05].
      CONCLUSIONS: In patients with myocarditis, CK-MB mass and cTnI both follow a
      consistent pattern of change: elevated in the acute stage of the disease but
      return to normal after recovery. In patients with muscular diseases, these 2
      indexes have different pattern of change. CK-MB mass is significantly higher than
      control even after the treatment, while cTnI value remain unchanged. Therefore,
      CK-MB mass has very limited value as an index for myocardial injury in these
      patients.

PMID- 22153009
TI  - [Tirofiban improved the prognosis of senior acute coronary syndrome patients
      received percutaneous coronary intervention].
AB  - OBJECTIVE: To examine if tirofiban may improve the prognosis in aged acute
      coronary syndrome (ACS) patients received percutaneous coronary intervention
      (PCI). METHODS: Three hundred and twenty-five ACS patients (age >= 60 years), all
      received drug-eluting stents implantation, were assigned into tirofiban group (n
      = 210) to receive tirofiban+aspirin and clopidogrel and control group (n = 115)
      to received aspirin and clopidogrel only. The incidence of thrombolysis in
      myocardial infarction (TIMI) grade 3 after PCI, in-stent thrombosis,
      slight/severe bleeding, platelet decrease, myocardial infarction (MI) and target
      vessel revascularization (TVR) within 30 days and 12 months after PCI and 30 days
      and 12 months mortality post PCI. RESULTS: In comparison with the control group,
      the tirofiban group had significantly higher TIMI grade 3 flow after PCI (99.05%
      vs. 94.78%, P < 0.05), lower in-stent thrombosis (0.47% vs. 2.61%, P < 0.05), as
      well as lower mortality, MI, and TVR in 30 days and 12 months after PCI (30 days:
      0, 0.47% and 0.47% vs. 2.61%, 3.48% and 2.61%; 12 months: 0, 0.47% and 0.47% vs.
      2.61%, 5.22% and 5.22%, P < 0.05 or P < 0.01). No significant difference was
      found (both P > 0.05) in slight bleeding (7.14% vs. 4.35%) and severe bleeding (0
      vs. 0) between tirofiban group and control group. A slight difference in
      thrombocytopenia was found between tirofiban group and control group (0.95% vs.
      0), but it failed to reach the level of statistical significance (P > 0.05).
      CONCLUSIONS: Tirofiban may improve the TIMI grade flow in senior ACS patients
      after PCI. It also decreases the incidence of in-stent thrombosis, mortality, MI,
      and TVR in 30 days and 12 months after PCI, without causing increase in severe
      bleeding and platelet penia. Therefore, it may improve the short/long-term
      prognosis for these patients.

PMID- 22153010
TI  - [L-arginine suppresses ischemia/reperfusion induced up-regulation of endothelin-1
      production in a rat model of acute myocardial injury].
AB  - OBJECTIVE: To examine the level of endothelin-1 (ET-1) in serum and its
      expression in myocardium tissue during the development of acute myocardial
      ischemia/reperfusion (I/R) injury in rat and the effects of L-arginine (L-Arg)
      administration on these indexes. METHODS: One hundred and ten Wistar rats were
      randomly divided into nine groups to receive: (1) sham surgery, (2)ischemia (I,
      by ligation of anterior descending coronary artery for 30 minutes), (3)
      I+reperfusion (R, by the removal of the ligature) for 0.5 hour, (4) I+R for 1
      hour, (5) I+R for 2 hours; group (6) ~ (9) also received I/R treatment as in
      group 2 ~ 5 respectively but with L-Arg pretreatment. Blood and myocardium tissue
      samples were collected by the end of the experiment for the analysis of: serum
      level of creatine kinase (CK), lactate dehydrogenase [LDH, by enzyme linked
      immunosorbent assay (ELISA)], ET-1 (radioimmunoassay), and the tissue content of
      ET-1 mRNA/peptide [by reverse-transcription polymerase chain-reaction (RT-PCR)
      and Western blotting]. RESULTS: In comparison with the sham treated control
      animals, the serum levels of CK, LDH, and ET-1 were all significantly higher in
      the groups treated with I/R (particularly those exposed to reperfusion). The
      myocardial tissue content of ET-1 mRNA/peptide were also significantly increased
      in I/R treated groups (particularly the I+R 2 hours group) as compared to control
      (ET-1 mRNA: 0.775 +/- 0.029 vs. 0.310 +/- 0.076; ET-1 peptide: 0.773 +/- 0.055
      vs. 0.340 +/- 0.099, both P < 0.05). The i.v. administration of L-Arg
      significantly suppressed the up-regulation of tissue content of ET-1 mRNA
      /peptide in I/R treated animals (ET-1 mRNA: 0.340 +/- 0.049 vs. 0.775 +/- 0.029;
      ET-1 peptide: 0.390 +/- 0.094 vs. 0.773 +/- 0.055, both P < 0.05). CONCLUSION: L
      Arg may be tested during certain stage of I/R injury as a therapeutic
      intervention for the suppression of ET-1 up-regulation.

PMID- 22153011
TI  - [The lung injury in postpartum and non-pregnant rabbits after resuscitation from
      hemorrhagic shock].
AB  - OBJECTIVE: To investigate the difference in the development of acute lung injury
      after hemorrhagic shock in postpartum and non-pregnant rabbits. METHODS:
      Hemorrhagic shock/resuscitation was produced on 9 pregnant New-Zealand rabbits
      postpartum (within 24 hours after giving birth) and 9 non-pregnant controls via
      carotid artery bleeding and perfusion (i.v.) of lactate Ringer solution for 3
      hours. The serum level of cytokine tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-10 (IL-10) in the animals were measured at different time points.
      Lung tissue were taken 3 hours after resuscitation for the determination of
      malondialdehyde (MDA),the activity of superoxide dismutase (SOD), myeloperoxidase
      (MPO), dry/wet weight (D/W), nuclear factor-KappaB (NF-KappaB), and mRNA content
      of intercellular adhesion molecule-1 (ICAM-1). RESULTS: Serum TNF-alpha (ng/L)
      and IL-10 (ng/L) in antepartum pregnant rabbits were not significantly different
      from non-pregnant rabbits (TNF-alpha: 87.6 +/- 6.8 vs. 83.2 +/- 5.3; IL-10: 44.9
      +/- 3.9 vs. 42.7 +/- 3.4, both P > 0.05). However, the serum TNF-alpha increased
      significantly after delivery (102.5 +/- 8.1 vs. 87.6 +/- 6.8, P < 0.05). TNF
      alpha and IL-10 increased 1 hour after shock in both postpartum and non-pregnant
      rabbits. The serum TNF-alpha in postpartum rabbits was significant higher than
      non-pregnant rabbits in each resuscitation period (1 hour: 230.0 +/- 14.9 vs.
      202.0 +/- 10.1, 2.5 hours: 290.0 +/- 18.6 vs. 236.0 +/- 14.4, 4 hours: 265.0 +/-
      15.9 vs. 217.0 +/- 12.8, all P < 0.05), meanwhile the serum IL-10 in postpartum
      animals was significantly lower than the non-pregnant controls(1 hour: 104.3 +/-
      6.9 vs. 135.0 +/- 7.8, 2.5 hours: 146.8 +/- 9.4 vs. 178.3 +/- 11.7, 4 hours:
      126.0 +/- 7.9 vs. 165.8 +/- 9.6, all P < 0.05). The value of MDA, MPO, D/W, NF
      KappaB activity and ICAM-1 mRNA content in lung tissue of postpartum rabbits were
      all significant higher than non-pregnant rabbits after resuscitation [MDA
      (nmol/mg): 52.6 +/- 5.9 vs. 39.4 +/- 4.7, MPO (U/mg): 4.62 +/- 0.85 vs. 3.26 +/-
      0.62, D/W: 0.186 +/- 0.025 vs. 0.143 +/- 0.016, NF-KappaB activity (A value):
      0.89 +/- 0.27 vs. 0.46 +/- 0.15, ICAM-1 mRNA: 4.6 +/- 1.2 vs. 2.5 +/- 0.7, all P
      < 0.05], but the activity of SOD (U/mg) was lower (47.8 +/- 6.7 vs. 63.5 +/- 8.2,
      P < 0.05) in the controls after resuscitation. CONCLUSIONS: Delivery causes
      significant increase in serum TNF-alpha in pregnant rabbits. Inflammatory lung
      injury is more severe in postpartum rabbits after resuscitation from hemorrhagic
      shock, and the increased serum level of inflammatory mediators may be part of the
      mechanism for such difference.

PMID- 22153012
TI  - [The impact of L-carnitine administration on the serum level of myocardium injury
      markers in patients with acute carbon monoxide poisoning].
AB  - OBJECTIVE: To examine the serum level of myocardial injury markers in patients
      with carbon monoxide (CO) poisoning, the correlation between these markers and
      the severity of the disease, and the therapeutic effects of L-carnitine
      administration. METHODS: 69 patients, chosen from 309 cases of acute carbon
      monoxide poisoning (ACOP) for abnormally high level of serum myocardial injury
      markers (myoglobin, Mb; MB isoenzyme of creatine kinase, CK-MB; cardiac troponin
      I, cTnI) at the time of admission, were randomly divided into control group (n =
      34) and observation group (n = 35). The patients in control group were given
      Xingnaojing (20 ml/d i.v. drip), and the observation group Xingnaojing (20
      ml/d)+L-carnitine (2 g/d i.v. drip), in addition to the conventional oxygen
      supply and symptom-focused therapy. The plasma concentration of carboxyhemoglobin
      (HbCO, as index for CO poisoning severity), Mb, CK-MB, and cTnI in these patients
      were further examined 24 hours, 72 hours and 1 week after the treatment, for
      difference between the two groups, and the correlation between the serum level of
      HbCO and the myocardial injury markers. RESULTS: At the time of admission, the
      incidence of abnormal findings in myocardial injury markers were 2.5% (5/204),
      46.8% (36/77) and 100.0% (28/28) in patients with mild (HbCO: 10% ~ 19%),
      moderate (20% ~ 39%) and severe (>=40%) CO poisoning, respectively. The incidence
      of abnormal findings in injury markers was significantly correlated to the HbCO
      concentration (x(2)=170.3549, P < 0.0001). Before the treatment, no significant
      difference was found in any of the indexes [HbCO: (31.1 +/- 17.6)%, (32.3 +/-
      16.9)%, Mb (MUg/L): 154.2 +/- 51.8, 165.4 +/- 48.6, CK-MB (MUg/L): 8.7 +/- 3.3,
      9.6 +/- 3.8), and cTnI (MUg/L): 2.7 +/- 1.2, 2.8 +/- 1.5, all P > 0.05] between
      the control and observation group. However, it was found in: Mb (24 hours: 74.0
      +/- 36.5 vs. 97.1 +/- 35.8, 72 hours: 40.1 +/- 6.8 vs. 69.0 +/- 11.2), cTnI (24
      hours: 1.9 +/- 0.5 vs. 2.3 +/- 0.7, 72 hours: 1.2 +/- 0.3 vs. 1.8 +/- 0.4) both
      24 hours and 72 hours after the treatment, and CK-MB, 24 hours after treatment
      (10.6 +/- 4.1 vs. 13.0 +/- 3.9) with the values in observation group
      significantly lower (P < 0.05 or P < 0.01); 1 week after the treatment, the
      concentration of all the injury markers returned to the normal levels with no
      significant difference between the two groups. Meanwhile, no significant
      difference was found between the two groups in HbCO concentration throughout the
      due-course of the therapy. CONCLUSIONS: The incidence of abnormal findings in
      serum myocardial injury markers was positively correlated with HbCO concentration
      after CO poisoning. L-carnitine may protect the myocardium and striated muscles
      against injury in patients with CO poisoning.

PMID- 22153013
TI  - [The effects of mild hypothermia on cardiac function and myocardial structure in
      a rabbits model of ventricular fibrillation after restoration of spontaneous
      circulation].
AB  - OBJECTIVE: To examine the impact of mild hypothermia on cardiac function,
      myocardial tissue integrity, and 48 hours mortality in a rabbits model of
      ventricular fibrillation after restoration of spontaneous circulation (ROSC).
      METHODS: The rabbits were randomly divided into four groups: normothermic post
      ROSC (NTPR, n = 10), mild hypothermia post ROSC (HTPR, n = 10), normothermic
      control (NTC, n = 8) and mild hypothermia control (HTC, n = 8). Ventricular
      fibrillation was induced by trans-epicardium electric-shook with alternating
      current in all the animals and ROSC was achieved through administration of
      adrenaline (i.v.) and artificial ventilation in group NTPR and HTPR. The body
      temperature of the animals was kept either at (39.0 +/- 0.5) centigrade (NTPR and
      NTC) or (33.5 +/- 0.5) centigrade (HTPR and HTC) for 4 hours after surgery for
      hemodynamic index data collection 0.5, 1, 2, 3 and 4 hours after surgery, 48
      hours later, the mortality in the animals was recorded, and myocardial tissue
      samples were collected from survived animals for morphological examination by
      light and electric microscopy and analysis of apoptosis by terminal
      deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. The
      content of ATP, ADP and AMP in the tissue samples was measured by high
      performance liquid chromatography (HPLC) for the calculation of energy charges
      (EC). RESULTS: (1)Hemodynamic indexes: as compared to the NTC group, HTC group
      exhibited significantly lower levels of heart rate (HR) and -dp/dt max in all the
      time points. No significant difference between the two groups in the levels of
      +dp/dt max and mean artery pressure (MAP) was found in all the time points but
      0.5 hour. There was no significant difference in the levels of left ventricular
      end-diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP),
      and femoral artery blood pressure between the two groups.(2) In comparison with
      NTPR group, HTPR group exhibited significantly (all P < 0.05) lower levels of HR
      (bpm) and -dp/dt max in all time points (ROSC 0.5, 1, 2, 3, 4 hours: HR 216.5 +/-
      33.3 vs. 292.9 +/- 38.4, 218.2 +/- 28.0 vs. 294.3 +/- 37.0, 227.5 +/- 25.4 vs.
      291.4 +/- 25.3, 232.4 +/- 27.4 vs. 278.1 +/- 30.8, 230.6 +/- 22.0 vs. 285.1 +/-
      38.2; -dp/dt max 1847.1 +/- 241.2 vs. 2383.3 +/- 470.9, 1860.7 +/- 167.8 vs.
      2154.6 +/- 319.5, 1822.3 +/- 389.7 vs. 2239.7 +/- 379.0, 1950.6 +/- 412.9 vs.
      2229.6 +/- 392.4, 1875.7 +/- 555.6 vs. 2396.7 +/- 420.1). There was no
      significant difference between the two groups in the levels of LVEDP, +dp/dt max,
      LVESP, and femoral artery blood pressure. (3)Optical and electron microscopy
      revealed myocardium injury in samples from animals underwent ROSC. However, in
      comparison with the NTPR group, samples from HTPR group exhibited less damage to
      the myocardium structure. (4) Apoptosis index (AI) of myocardium was
      significantly (P < 0.05) higher in NTPR group (42.02%) than in HTPR group
      (26.39%). (5) Tests of myocardial energy: ATP level (MUmol/g) in HTPR was
      significantly (P < 0.05) higher than NTPR (0.97 +/- 0.26 vs. 0.65 +/- 0.16). EC
      in NTPR was significant lower than it in two control groups [(0.33 +/- 0.13)% vs.
      (0.52 +/- 0.12)%, (0.55 +/- 0.06)%, both P < 0.05], whereas no such difference
      was found between HTPR [(0.41 +/- 0.12)%] and two control groups. (6) 48 hours
      survival rate in HTPR group was significantly higher (P = 0.043) as compared to
      NTPR group (100% vs. 60%). CONCLUSIONS: Myocardial dysfunction and myocardium
      tissue injury both develop in post-resuscitation rabbits with ventricular
      fibrillation. In these animals, reducing body temperature to the level of mild
      hypothermia after ROSC may improve the 48 hours survival rate, probably via
      mechanisms that suppress myocardial cell apoptosis. In our study, such
      intervention produced no obvious negative impact neither on the cardiac function
      nor hemodynamics.

PMID- 22153014
TI  - [Goal-directed renal replacement therapy for acute kidney injury after cardiac
      surgery].
AB  - OBJECTIVE: To compare the efficacy and safety of goal-directed renal replacement
      therapy(GDRRT) and daily high volume hemofiltration (dHVHF) in the treatment of
      acute kidney injury (AKI) after cardiac surgery. METHODS: Clinical data from 128
      patients received either GDRRT (n = 64) or dHVHF (n = 64) for AKI after cardiac
      surgery were analyzed retrospectively. parameters examined included: urea
      nitrogen, serum creatinine (SCr, before and after treatment), heart rate, mean
      artery pressure (MAp, recorded within 72 hours after the initiation of renal
      replacement therapy). The hospital mortality, day-28 mortality, renal function
      recovery rate, and the incidence of adverse events in the two groups were also
      compared. RESULTS: The hospital mortality was 43.75% for both GDRRT and dHVHF
      treated patients (group). The day-28 mortality in GDRRT group were slightly
      lower, but the difference was not significant (43.75% vs. 57.81%, P = 0.055).
      Also no significant difference was found between the two groups in hospital stay.
      The patients received dHVHF had longer intensive care unit (ICU) stay (hours) and
      duration of mechanical ventilation (days) as compared to the patients received
      GDRRT [356.5 (176.3, 554.6) vs. 238.3 (119.6, 440.9), P = 0.023; 8.0 (5.0, 16.0)
      vs. 6.0 (3.0, 13.5), P = 0.042]. The logistic regression analyses showed that
      complete renal function recovery rate in GDRRT group was significantly higher
      (39.1% vs. 18.8%, P < 0.01). The partial renal function recovery rate in GDRRT
      group was slightly lower but not statistically different from dHVHF group (3.1%
      vs. 9.4%, P > 0.05). In dHVHF group, the maximum SCr during the treatment, and
      the SCr before discharge were both significantly higher than GDRRT group
      (MUmol/L: SCr maximum 559.0 +/- 236.0 vs. 440.4 +/- 192.0, SCr before discharge
      381.4 +/- 267.0 vs. 271.2 +/- 164.4, both P < 0.01). No significant difference
      was found between the two groups in incidence of hypotension (35.9% vs. 37.5%)
      and MAP (mm Hg, 1 mm Hg=0.133 kPa, 82 +/- 13 vs. 81 +/- 15) 72 hours into the
      therapy (both P > 0.05). The incidence of tachycardia, and incidence of blood
      coagulation were both higher in dHVHF group (78.1% vs. 59.4%, 35.9% vs. 20.3%,
      both P < 0.05). However, the hospitalization expense (thousand yuan) was
      significantly higher for dHVHF group (15.00 +/- 2.80 vs. 9.85 +/- 3.00, P <
      0.01). CONCLUSION: For patients with post-cardiac surgery AKI, GDRRT and dHVHF
      are very similar in terms of short-term survival rate and safety. But GDRRT is
      superior for renal function recovery and cost saving.

PMID- 22153015
TI  - [The effects of joint administration of 6% hydroxyethyl starch 130/0.4 and high
      volume hemofiltration on patients with acute lung injury and acute kidney
      injury].
AB  - OBJECTIVE: To evaluate the effects of administration of 6% hydroxyethyl starch
      (6% HES 130/0.4, voluven) in combination with high volume hemofiltration (HVHF)
      in patients with ALI and AKI. METHODS: One hundred and eight patients with acute
      lung injury (ALI) and acute kidney injury (AKI) were enrolled from Department of
      Intensive Care Unit (ICU) of the provincial Hospital Affiliated to Shandong
      University between August 2006 and May 2011. The patients were randomly divided
      into two groups A (n = 68) and B (n = 40) to receive voluven (i.v., for volume
      resuscitation) and voluven+HVHF for 72 hours. The arterial blood lactate
      concentration (Lac), high sensitivity C-reactive protein (hs-CRP) serum
      concentration, pulmonary function index alveolar-arterial oxygen pressure
      difference [P(A-a)DO2] and oxygenation index (OI), as well as kidney function
      index serum cystatin C (Cyst C) and serum creatinine clearance rate (CCr) were
      measured at the time of admission and 72 hours after the treatment for
      statistical analysis. RESULTS: In comparison with group A, group B had
      significantly (all P < 0.01) lower mean value in the level of arterial Lac
      (mmol/L: 1.7 +/- 0.7 vs. 2.7 +/- 1.5), serum hs-CRP (mg/L: 35.8 +/- 18.8 vs. 99.5
      +/- 20.4), P(A-a)DO2 (mm Hg, 1 mm Hg=0.133 kPa: 115.5 +/- 23.1 vs. 155.4 +/-
      27.4), Cyst C (mg/L: 2.06 +/- 1.12 vs. 3.95 +/- 2.06) and significantly higher
      (both P < 0.01) mean value of OI (mm Hg: 295.2 +/- 38.8 vs. 239.5 +/- 32.7) and
      CCr (ml/min: 108.71 +/- 31.33 vs. 90.21 +/- 30.35) 72 hours after treatment. The
      mortality rate of group B was significantly lower than group A [10.00%(4/40) vs.
      29.41%(20/68), P < 0.05] 7 days after the admission. CONCLUSION: 6% HES 130/0.4
      in combination with HVHF could improve the lung and kidney function of the
      patients with ALI and AKI, prevent the development of multiple organ dysfunction
      syndrome (MODS), therefore improve the survival rate of these patients.

PMID- 22153016
TI  - [The sensitivity and accuracy of RIFLE and AKIN criteria for acute kidney injury
      diagnosis in intensive care unit patients].
AB  - OBJECTIVE: To evaluate the sensitivity/accuracy of 2 different acute kidney
      injury (AKI) diagnosis/classification criteria, the RIFLE (risk, injury, failure,
      loss of kidney function, end-stage kidney disease) and the acute kidney injury
      network (AKIN), for patients in intensive care unit (ICU). METHODS: Clinical data
      were collected from all adult patients admitted to the Department of Intensive
      Medicine in Guangdong General Hospital between October 2009 and July 2010, and
      AKI cases were identified/classified using RIFLE and AKIN criteria separately,
      for statistical evaluation of their diagnostic sensitivity, and accuracy in
      hospital mortality prediction. RESULTS: In all 524 patients evaluated, AKI were
      identified by RIFLE criteria in 95 of them, while by AKIN, 135. The AKI incidence
      by RIFLE (18.1%), and AKIN (25.8%) were significantly different (P < 0.05).
      Meanwhile, AKI incidence was found independent from the mortality, either by
      RIFLE or AKIN (both P < 0.001). In all patients, the area under the receiver
      operator characteristic curve (ROC curve), the index for hospital mortality
      prediction, was 0.7293 for RIFLE [with 95% confidence interval (95%CI) ranging
      from 0.6005 to 0.8581, P < 0.001], and for AKIN, 0.7777 (95%CI: 0.6664 - 0.8890,
      P < 0.001). No significant difference was found between the total hospital
      mortality by the two criteria (37.9% vs. 34.1%, P > 0.05). CONCLUSION: Although
      AKIN criteria has higher sensitivity in AKI diagnosis, it is not different from
      the RIFLE criteria in predicting hospital mortality in critically ill patients.

PMID- 22153017
TI  - Initial construction of a maladaptive personality trait model and inventory for
      DSM-5.
AB  - BACKGROUND: DSM-IV-TR suggests that clinicians should assess clinically relevant
      personality traits that do not necessarily constitute a formal personality
      disorder (PD), and should note these traits on Axis II, but DSM-IV-TR does not
      provide a trait model to guide the clinician. Our goal was to provide a
      provisional trait model and a preliminary corresponding assessment instrument, in
      our roles as members of the DSM-5 Personality and Personality Disorders Workgroup
      and workgroup advisors. METHOD: An initial list of specific traits and domains
      (broader groups of traits) was derived from DSM-5 literature reviews and
      workgroup deliberations, with a focus on capturing maladaptive personality
      characteristics deemed clinically salient, including those related to the
      criteria for DSM-IV-TR PDs. The model and instrument were then developed
      iteratively using data from community samples of treatment-seeking participants.
      The analytic approach relied on tools of modern psychometrics (e.g. item response
      theory models). RESULTS: A total of 25 reliably measured core elements of
      personality description emerged that, together, delineate five broad domains of
      maladaptive personality variation: negative affect, detachment, antagonism,
      disinhibition, and psychoticism. CONCLUSIONS: We developed a maladaptive
      personality trait model and corresponding instrument as a step on the path toward
      helping users of DSM-5 assess traits that may or may not constitute a formal PD.
      The inventory we developed is reprinted in its entirety in the Supplementary
      online material, with the goal of encouraging additional refinement and
      development by other investigators prior to the finalization of DSM-5. Continuing
      discussion should focus on various options for integrating personality traits
      into DSM-5.

PMID- 22153018
TI  - Urologic chronic pelvic pain.

PMID- 22153019
TI  - Photodynamic inactivation of viruses using upconversion nanoparticles.
AB  - Photodynamic therapy (PDT) is a promising treatment modality that utilizes light
      of an appropriate wavelength to excite photosensitive materials called
      photosensitizers, which upon excitation, generate reactive oxygen species (ROS)
      that are cytocidal and virucidal. However, problems such as hydrophobicity of
      photosensitizers and limited tissue penetration ability of the current light
      sources impeded its promotion as a mainstay in medical technology. Here, by using
      near-infrared (NIR)-to-visible upconversion nanoparticles (UCNs), we demonstrate
      UCN-based photodynamic inactivation as a potential antiviral strategy. These UCNs
      are nanotransducers which not only act as carriers of photosensitizers but also
      active participants in PDT by transducing NIR radiation to visible emissions
      appropriate for excitation of the attached photosensitizers. The UCNs effectively
      reduced the infectious virus titers in vitro with no clear pathogenicity in
      murine model and increased target specificity to virus-infected cells. Hence,
      this is a promising antiviral approach with feasible applications in the
      treatments of virus-associated infections, lesions and cancers.

PMID- 22153020
TI  - Inhibitive effects of quinestrol on male testes in Mongolian gerbils (Meriones
      unguiculatus).
AB  - The current study evaluated effects of quinestrol on oxidative stress and
      abnormal spermatogenesis for male Mongolian gerbils. Gerbils were randomly
      divided into multi-dose treated, single-dose treated, control groups. At 15 days
      after treatment antioxidant enzymes (SOD, GSH-Px) activities and T-AOC were
      decreased whereas the MDA concentration was significantly increased, testicular
      weight and seminiferous tubular areas decreased, germ cells were rarefied and
      showed irregular distribution in seminiferous tubules, apoptosis was pronounced
      among spermatocytes and spermatids, the number of dead and abnormal acrosomes of
      spermatozoa increased significantly in quinestrol treated groups. At 30 days
      following treatment the testicular histopathological changes were more severe,
      sperm quality and antioxidant capacity continued to decline, and multi-dose
      treatment produced more damage to gerbils testes compared with single-dose
      treatment. The physiological indicators were recovered by 60 days of treatment
      withdrawal. The results showed oxidative stress induced by quinestrol in relation
      to abnormal spermatogenesis.

PMID- 22153021
TI  - Assessment of mast cells degranulation in rainbow trout (Oncorhynchus mykiss
      Walbaum) by means of gray level and texture analysis (Gray Level Correlation
      Matrices).
AB  - Degranulation of intestinal mast cells in rainbow trout (Oncorhynchus mykiss
      Walbaum) was studied by means of image analysis technique. Two strips from the
      same intestinal segment from ten clinically healthy trout were sampled. One was
      immediately mounted in an organ bath, treated with compound 48/80 and then
      processed, as the remnant untreated strip, for light microscopy. Colour pictures
      taken from each section were converted in their gray levels RGB stacks equivalent
      and in 8 bits gray levels. Five granular cytoplasm areas of mast cells (MCs) for
      each section were analysed for the following parameters: mean gray values and
      Gray Level Correlation Matrices parameters. All RGB channels and the 8 bit gray
      levels transformed images showed higher mean gray level values after compound
      48/80 exposure (Anova, p<0.01). Only two channels (Red and Green) and the 8 bit
      gray levels transformed images of a unique texture parameter (contrast) appeared
      to be significantly higher after compound 48/80 exposure (Anova, p<0.05). Red
      channel and Blue channel means gray level values were able to discriminate
      between not degranulated and degranulated MCs. The described model represents a
      promising alternative in mast cell research.

PMID- 22153022
TI  - How randomized controlled trials (RCTs) can be misleading: introduction.

PMID- 22153023
TI  - Influence and critique of the EVAR 1 Trial.
AB  - This article summarizes a differing interpretation of the long-term results of
      the Endovascular Aneurysm Repair (EVAR) 1 Trial. The EVAR 1 Trialists'
      conclusions regarding the equivalence of long-term outcomes of endovascular
      aneurysm repair (EVAR) with those of open repair (OR) are misleading and not
      applicable to patients currently treated by EVAR. The reasons that the EVAR 1
      Trial is misleading and casts an unfairly negative light on the superiority of
      EVAR are as follows: (1) The convergence of all-cause mortality curves or the
      "catch-up" phenomenon; (2) old technology, inexperience, and outdated secondary
      treatment; (3) complications were not well-defined in EVAR 1 and are not
      applicable to current practice; and (4) the unfair cost comparison between EVAR
      and OR. The implication that OR is equivalent or superior to EVAR is, therefore,
      a misrepresentation. EVAR is a better treatment for infrarenal aortic aneurysms
      in anatomically suitable patients. We believe that current standards of practice
      should be altered accordingly, rather than preserving the nostrums that EVAR and
      OR are equivalent and that EVAR has more intrinsic disadvantages.

PMID- 22153024
TI  - Influence and critique of the PIVOTAL and the EVAR 2 Trials.
AB  - Management of a condition that has potentially life-threatening consequences may
      not lend itself effectively to the scrutiny of a randomized clinical trial when
      an observation or no treatment option is offered as part of the trial. This type
      of trial often experiences a significant rate of crossover of subjects from no
      treatment to treatment, and when results are analyzed on an intent-to-treat
      basis, they may fail to resolve the issue under study. These trials are
      frequently used as Level 1 medical evidence and the potential impact on clinical
      decision-making and reimbursement can be quite significant and long-lasting. The
      authors observed this phenomenon during participation in the Positive Impact of
      Endovascular Options for Treating Aneurysms Early (PIVOTAL) trial and have
      observed it in an analysis of the Endovascular Aneurysm Repair 2 (EVAR 2) trial.
      Possible solutions to mitigate the high crossover effect are offered for
      consideration. Some clinical conditions dealing with potentially life-threatening
      problems probably do not lend themselves to be studied in randomized prospective
      clinical trials containing an observation or no treatment arm.

PMID- 22153025
TI  - Influence and critique of CREST and ICSS Trials.
AB  - The principle findings of the Carotid Revascularization Endarterectomy Versus
      Stenting Trial and the International Carotid Stenting Study are reviewed and
      discussed. Flaws and possible weaknesses in both trials are highlighted. The
      possibility that some Carotid Revascularization Endarterectomy Versus Stenting
      Trial conclusions have been misinterpreted in ways not justified by the trial's
      data is considered. This possibility may have prompted one conclusion of a recent
      American Heart Association Guideline on the management of carotid artery disease
      to be misleading.

PMID- 22153026
TI  - Direct thrombin inhibitors for the treatment of venous thromboembolism: analysis
      of the Dabigatran versus Warfarin clinical trial.
AB  - Vitamin-K antagonists have played a dominant role in the long-term management of
      patients with venous thromboembolism, and large trials from the past decade
      reinforced warfarin's effectiveness as an intermediate-duration and extended
      duration anticoagulant. However, promising new oral direct thrombin inhibitors
      are proving to be at least as effective and as safe as the vitamin-K antagonists,
      without the associated hepatic toxicity that was seen with earlier orally
      administered direct thrombin inhibitors. This article reviews the recently
      published Dabigatran versus Warfarin in the Treatment of Acute Venous
      Thromboembolism clinical trial, and discusses the limitations and clinical
      applicability of the trial, especially in comparison with vitamin-K antagonists
      and the recently studied oral direct factor Xa inhibitors, rivaroxaban and
      apixaban.

PMID- 22153027
TI  - Influence and critique of the ASTRAL and CORAL Trials.
AB  - Optimal management of renal artery atherosclerotic occlusive disease has been
      widely debated and studied. Although the accepted invasive treatment has evolved
      into favoring balloon angioplasty and stenting, the indications for intervention
      or medical therapy have not been universally agreed upon. The Angioplasty and
      Stenting for Renal Artery Lesions (ASTRAL) trial was conducted to answer the
      question of whether medical therapy or angioplasty and stenting is the best
      treatment for hemodynamically significant renal artery stenosis. However, the
      ASTRAL trial's study design was faulty and therefore did not provide conclusive
      evidence to answer the question. The Cardiovascular Outcomes in Renal
      Atherosclerotic Lesions (CORAL) trial was designed to answer the same question as
      to which treatment (medical or angioplasty and stent) is best for renal artery
      stenosis, and its methodologies took into consideration the weaknesses of the
      ASTRAL trial. Results are soon to be released.

PMID- 22153028
TI  - Influence and critique of the INSTEAD Trial (TEVAR versus medical treatment for
      uncomplicated type B aortic dissection).
AB  - Endovascular stent-grafting represents a novel nonsurgical therapeutic concept
      for type B aortic dissection in both the acute and subacute/chronic settings with
      unknown impact on outcomes. In a prospective trial, 140 patients with clinically
      stable type B dissection were randomly subjected to elective stent-graft
      placement in addition to optimal medical therapy (n = 72) or to optimal medical
      therapy (n = 68) with surveillance (arterial pressure according to World Health
      Organization guidelines, <=120/80 mm Hg) and recurrent computed tomography
      imaging. Primary endpoint was 2-year all-cause mortality, while aorta-related
      mortality, progression of disease (with need for crossover to stent-graft or
      additional endovascular or open surgery), and aortic remodeling were secondary
      endpoints. There was no difference in all-cause mortality at 2 years, with
      cumulative survival of 95.6% +/- 2.5% with optimal medical therapy versus 88.9%
      +/- 3.7% with thoracic endovascular aortic repair (TEVAR) (P = .15). Considering,
      however, that only 40% of the expected events occurred within 2 years (based on
      registry data), the trial turned out to be underpowered for all-cause mortality.
      Moreover, aorta-related mortality was also not different (P = .44) within the
      first 2 years of follow-up, and risk for the combined endpoints of aorta-related
      death (rupture) and progression (including conversion or additional endovascular
      or open surgery) was similar (P = .65); three neurological adverse events
      occurred in the TEVAR group (one paraplegia, one stroke, and one transient
      paraparesis) versus one paraparesis with medical treatment. Finally, and as
      expected, aortic remodeling (with true lumen recovery and thoracic false lumen
      thrombosis) occurred in 91.3% with TEVAR, but only in 19.4%with medical treatment
      alone (P < .001), suggestive of continued remodeling with TEVAR and failure of
      medical treatment to induce remodeling and healing of dissection. In conclusion,
      the data in the INSTEAD (Investigation of Stentgrafts in Aortic Dissection) trial
      show that in the setting of clinically stable, so-called uncomplicated type B
      aortic dissection, elective stent-graft placement on top of optimized medical
      management fails to improve survival and adverse events within an observation
      period of 2 years, despite favorable aortic remodeling.

PMID- 22153029
TI  - Influence and critique of the JUPITER Trial (Statins v no statins for primary
      prevention of cardiovascular events in patients with normal lipids and elevated C
      reactive protein).
AB  - Perhaps no recent trial in primary prevention of cardiovascular disease has
      resulted in more controversy than the JUPITER (Justification for the Use of
      Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial,
      which was first published in 2008. The study evaluated a patient cohort
      previously considered to be "healthy," ie, men 50 years of age or older and women
      60 years of age or older, who did not have a history of cardiovascular disease
      and, at the initial screening visit, had a low-density lipoprotein cholesterol
      level of <130 mg/dL (3.4 mmol/L) and a high-sensitivity C-reactive protein level
      >=2.0 mg/L. The trial showed that rosuvastatin is a powerful statin that, at
      lower doses, can reduce low-density lipoprotein cholesterol to levels previously
      not seen with other agents. Concurrently, it can also reduce high-sensitivity C
      reactive protein to levels below what are considered normal, but that might be
      more physiologic. In the trial participants who achieved such lowering, major
      cardiovascular events, including venous thromboembolic events, were reduced even
      in the short term. Despite these results, many still question whether the trial
      results should influence high-sensitivity C-reactive protein testing or the
      prescription of statins for individuals at low risk for cardiovascular disease.

PMID- 22153030
TI  - Necrosis assessment in renal carcinoma.

PMID- 22153032
TI  - Estimation of sensitivity and specificity of five serological tests for the
      diagnosis of porcine brucellosis.
AB  - While serological tests are essential in surveillance and control programs of
      animal diseases, to date none of the common serological tests approved in the EU
      (complement fixation test or Rose-Bengal test) has been shown to be reliable in
      routine individual diagnosis of porcine brucellosis, and some more recent tests
      like ELISA have not been fully evaluated yet. In the absence of a gold standard,
      this study allowed the estimation of sensitivities and specificities of these
      tests with a Bayesian approach using Markov Chain Monte Carlo algorithms. The pig
      population that was tested included 6422 animals from Metropolitan France. Serum
      samples were collected from a large population of pigs, representative of
      European swine population and tested with five brucellosis serological tests:
      Rose-Bengal test (RBT), fluorescence polarization assay (FPA), indirect ELISA (I
      ELISA) and two competitive ELISAs (C-ELISA). The sensitivity and the specificity
      of each test were estimated. When doubtful results were excluded, the most
      sensitive and specific test was C-ELISA(2) (Se C-ELISA(2)=0.964, [0.907; 0.994],
      95% credibility interval (CrI); Sp C-ELISA(2)=0.996, [0.982; 1.0], 95% CrI). When
      doubtful results were considered as negative, C-ELISA(2) was still the most
      sensitive and specific test (Se C-ELISA(2)=0.960, [0.896; 0.994], 95% CrI and Sp
      C-ELISA(2)=0.994, [0.977; 0.999], 95% CrI). The same conclusions were reached
      when doubtful results were considered as positive (Se C-ELISA(2)=0.963, [0.904,
      0.994], 95% CrI and Sp C-ELISA(2)=0.996, [0.986; 1.0], 95% CrI).

PMID- 22153033
TI  - Completeness of reporting in abstracts from clinical trials of pre-harvest
      interventions against foodborne pathogens.
AB  - Abstracts are the most commonly read part of a journal article, and play an
      important role as summaries of the articles, and search and screening tools.
      However, research on abstracts in human biomedicine has shown that abstracts
      often do not report key methodological features and results. Little research has
      been done to examine reporting of such features in abstracts from papers
      detailing pre-harvest food safety trials. Thus, the objective of this study was
      to assess the quality of reporting of key factors in abstracts detailing trials
      of pre-harvest food safety interventions. A systematic search algorithm was used
      to identify all in vivo trials of pre-harvest interventions against foodborne
      pathogens in PubMed and CAB Direct published from 1999 to October 2009.
      References were screened for relevance, and 150 were randomly chosen for
      inclusion in the study. A checklist based on the CONSORT abstract extension and
      the REFLECT Statement was used to assess the reporting of methodological features
      and results. All screening and assessment was performed by two independent
      reviewers with disagreements resolved by consensus. The systematic search
      returned 3554 unique citations; 356 were found to be relevant and 150 were
      randomly selected for inclusion. The abstracts were from 51 different journals,
      and 13 out of 150 were structured. Of the 124 abstracts that reported whether the
      trial design was deliberate disease challenge or natural exposure, 113 were
      deliberate challenge and 11 natural exposure. 103 abstracts detailed studies
      involving poultry, 20 cattle and 15 swine. Most abstracts reported the production
      stage of the animals (135/150), a hypothesis or objective (123/150), and results
      for all treatment groups (136/150). However, few abstracts reported on how
      animals were grouped in housing (25/150), the location of the study (5/150), the
      primary outcome (2/126), level of treatment allocation (15/150), sample size
      (63/150) or whether study units were lost to follow up (4/150). Forty-eight
      (48/150) abstracts reported the name, mode of administration, dose and duration
      of the intervention(s), while 102 (102/150) reported at least one of these
      elements. Nine (9/150) abstracts specified that allocation of study units to
      treatments was randomized, and none of the abstracts reported whether blinding
      was used (0/150). These results reveal gaps in reporting of methodological
      features and results. Thus, improving reporting quality in abstracts should be a
      crucial goal to be pursued by authors, reviewers and journal editors.

PMID- 22153034
TI  - Drug discovery in the age of systems biology: the rise of computational
      approaches for data integration.
AB  - The increased availability of large-scale open-access resources on bioactivities
      of small molecules has a significant impact on pharmacology facilitated mainly by
      computational approaches that digest the vast amounts of data. We discuss here
      how computational data integration enables systemic views on a drug's action and
      allows to tackle complex problems such as the large-scale prediction of drug
      targets, drug repurposing, the molecular mechanisms, cellular responses or side
      effects. We particularly focus on computational methods that leverage various
      cell-based transcriptional, proteomic and phenotypic profiles of drug response in
      order to gain a systemic view of drug action at the molecular, cellular and whole
      organism scale.

PMID- 22153035
TI  - Detection of pathogens in water: from phylochips to qPCR to pyrosequencing.
AB  - Waterborne pathogens pose a significant threat to human health and a proper
      assessment of microbial water quality is important for decision making regarding
      water infrastructure and treatment investments and eventually to provide early
      warning of disease, particularly given increasing global disasters associated
      with severe public health risks. Microbial water quality monitoring has undergone
      tremendous transition in recent years, with novel molecular tools beginning to
      offer rapid, high-throughput, sensitive and specific detection of a wide spectrum
      of microbial pathogens that challenge traditional culture-based techniques. High
      density microarrays, quantitative real-time PCR (qPCR) and pyrosequencing which
      are considered to be breakthrough technologies borne out of the 'molecular
      revolution' are at present emerging rapidly as tools of pathogen detection and
      discovery. Future challenges lie in integrating these molecular tools with
      concentration techniques and bioinformatics platforms for unbiased guide of
      pathogen surveillance in water and developing standardized protocols.

PMID- 22153036
TI  - [Breast MRI in 2011].

PMID- 22153037
TI  - [Breast MRI: Artefacts and pitfalls].
AB  - Multiple artefacts and pitfalls may occur with breast MRI. Artefacts are
      secondary to the MR technique itself while pitfalls often are the result of human
      error. The most common artefacts include motion, pulsation, chemical shift and
      magnetic susceptibility. The most common pitfalls include improper contrast
      injection, poor patient positioning, improper placement of the ROI and improper
      characterization of physiological and iatrogenic contrast enhancement. The
      identification of these artefacts and pitfalls on breast MR images may reduce
      their impact or even eliminate them. The use of optimized protocols is necessary.
      It is important to explain to patients the sequence of the examination, ensure
      proper placement of the breasts in the coil and optimize the contrast injection.
      The ROI should always be placed over the most suspicious region of the lesion.
      Finally, it is recommended to perform the MRI during the second week of the
      menstrual cycle and to discontinue the use of HRT 2 months prior to scanning when
      possible.

PMID- 22153038
TI  - [Acute mesenteric ischemia: Value of cross-sectional imaging].
AB  - Acute mesenteric ischemia (AMI) is a life-threatening emergency with prognosis
      directly correlated with the delay in diagnosis and treatment. Clinical and
      laboratory findings are nonspecific and it is imperative to look for findings of
      AMI on CT and ultrasound examinations performed in patients with acute abdomen.
      Arterial and venous ischemia are different entities with different clinical and
      imaging features, treatment and prognosis. The main causes of AMI are arterial
      thromboembolic disease and low-flow state. Venous ischemia is less frequent. Due
      to its high reported sensitivity (90%), CT should be performed as a firstline
      imaging modality when AMI is suspected. CT and ultrasound imaging features of AMI
      include: bowel wall thickness and enhancement abnormalities, pneumatosis, portal
      venous gas, demonstration of intravascular thrombus, bowel dilatation and
      ascitis.

PMID- 22153039
TI  - [Ultrasound of the tarsal tunnel: Normal and pathological imaging features].
AB  - Tarsal tunnel syndrome is a condition that is caused by compression of the tibial
      nerve or its associated branches. Diagnosis is based on clinical findings but
      imaging is performed to exclude a cause of compression, identified in 60 to 80%
      of cases. Ultrasound is a useful examination because of its high spatial
      resolution and ability to rapidly perform an axial survey of the nerves. The
      ultrasound imaging features of the tarsal tunnel are described. The etiologies
      and different types are illustrated through a review of clinical cases.

PMID- 22153040
TI  - [Value of contrast-enhanced ultrasound in the evaluation of indeterminate renal
      cysts on CT].
AB  - PURPOSE: To demonstrate the value of contrast-enhanced ultrasound (CEUS) in the
      management of Bosniak type 2F and 3 renal cysts on CT. PATIENTS AND METHODS:
      Retrospective study of 14 patients with 15 Bosniak type 2F and 3 renal cysts on
      contrast enhanced CT. All patients underwent CEUS of the kidneys after injection
      of SonoVue((r)). Using predetermined criteria, the lesions were classified as
      benign, malignant or indeterminate. Patients either underwent surgery or follow
      up CT at one to three years. RESULTS: From the 15 indeterminate cysts on CT, 12
      were either benign (n=8) or malignant (n=4) on CEUS. From the eight cysts
      considered benign on CEUS, seven remained stable on follow-up CT after a minimum
      of one year interval and one was surgically resected and confirmed to be benign.
      All four cysts considered malignant on CEUS were surgically resected and three
      were confirmed to be malignant and one was confirmed to be benign. Three cysts
      were indeterminate: two lesions were surgically resected and one was benign while
      the other was malignant and one lesion was stable at one year follow-up CT.
      CONCLUSION: CEUS was able to characterize indeterminate lesions as benign or
      malignant in 80% of cases with 92% reliability. Twenty percent of cysts remained
      indeterminate on CEUS. CEUS is reliable as a complement to CT in the evaluation
      of Bosniak type 2F and 3 renal cysts.

PMID- 22153041
TI  - [Metachronous pancreatic metastases from renal cell carcinoma: Role of imaging in
      a review of 17 cases with surgical correlation].
AB  - PURPOSE: To describe the imaging features of pancreatic metastases from renal
      cell carcinoma. PATIENTS AND METHODS: Retrospective study of 17 patients with
      isolated metachronous pancreatic metastases from renal cell carcinoma with
      surgical and pathological correlation. RESULTS: The preoperative diagnosis was
      made on ultrasound in 13 cases. Contrast-enhanced CT showed intense tumor
      enhancement at the arterial phase, mostly homogeneous but sometimes
      heterogeneous. There were multiple lesions in six cases. Following complete
      surgical resection, survival was fairly good. CONCLUSION: Long-term follow-up
      with CT obtained in the arterial and portal venous phases is mandatory. The
      arterial phase acquisition is essential for the diagnosis of pancreatic
      metastases from renal cell carcinoma.

PMID- 22153042
TI  - [Patient dose during interventional neuroradiology procedures: Results from a
      multi-center study].
AB  - PURPOSE: The purpose of this multicenter study was to determine the doses
      received by patients during interventional neuroradiology procedures and to
      consider establishing reference standards. MATERIALS AND METHODS: A retrospective
      study of nine interventional neuroradiology departments was conducted. Seven
      diagnostic (cerebral and spinal angiography) and therapeutic (embolization and
      vertebroplasty) procedures were reviewed. For each procedure, three dosimetric
      parameters were recorded: dose-area product (DAP), fluoroscopy time, and number
      of images. RESULTS: Results showed interdepartment variations, up to four-fold
      for diagnostic procedures and seven-fold for therapeutic procedures. However,
      applying the 75th percentile method to the entire dataset, reference standards
      can be proposed for six types of procedures including diagnostic cerebral
      angiography (230 Gycm(2)), follow-up selective cerebral angiography (80 Gycm(2)),
      aneurysm embolization (350 Gycm(2)), AVM embolization (440 Gycm(2)). Reference
      standards are also proposed with regards to fluoroscopy time and number of
      images. CONCLUSION: Such standards are useful for clinicians to evaluate and
      improve their practices.

PMID- 22153043
TI  - [Artery of Percheron occlusion: Value of MRI. A review of six cases].
AB  - Blood supply to the human thalami is complex and multiple variants exist. The
      artery of Percheron is one of those variants and is characterized by a solitary
      arterial trunk that branches from one of the proximal segments of either
      posterior cerebral artery and supplies blood to the paramedian thalami. Its
      occlusion results in bilateral paramedian thalamic infarction sometimes extending
      to the midbrain. We report six cases of bithalamic infarction secondary to
      occlusion of the artery of Percheron. We will illustrate the complex clinical
      symptomatology and underscore the role of imaging, especially MRI, for diagnosis.

PMID- 22153044
TI  - [Comment about the article: "Periprocedural management of hemostasis risk in
      interventional radiology"].

PMID- 22153045
TI  - [Anomalous origin of left coronary artery from the pulmonary artery: Evaluation
      with 64-slice scanner].

PMID- 22153046
TI  - [Pulmonary torsion following esophagectomy: A rare but life-threatening
      complication].

PMID- 22153047
TI  - [Chronic recurrent multifocal osteomyelitis: A case report in adult].

PMID- 22153048
TI  - [Bickerstaff's brainstem encephalitis: Report of two cases].

PMID- 22153049
TI  - [Stress fracture of the fibula].

PMID- 22153050
TI  - Mitral valve repair with artificial chordae: a review of its history, technical
      details, long-term results, and pathology.
AB  - Mitral valve repair is considered the procedure of choice for correcting mitral
      regurgitation in myxomatous disease, providing long-term results that are
      superior to those with valve replacement. The use of artificial chordae to
      replace elongated or ruptured chordae responsible for mitral valve prolapse and
      severe mitral regurgitation has been the subject of extensive experimental work
      to define feasibility, reproducibility, and effectiveness of this procedure.
      Artificial chordae made of autologous or xenograft pericardium have been replaced
      by chordae made of expanded polytetrafluoroethylene (PTFE), a material with the
      unique property of becoming covered by host fibrosa and endothelium. The use of
      artificial chordae made of PTFE has been validated clinically over the past 2
      decades and has been an increasing component of the surgical armamentarium for
      mitral valve repair. This article reviews the history, details of the relevant
      surgical techniques, long-term results, and fate of artificial chordae in mitral
      reconstructive surgery.

PMID- 22153051
TI  - Evolution of mitral valve replacement in children: a 40-year experience.
AB  - BACKGROUND: This report reviews our 40-year experience with pediatric mitral
      valve replacement (MVR) with respect to mortality, valve-related morbidity, and
      reoperation risk factors. METHODS: From 1970 to 2010, 97 patients have undergone
      a total of 136 MVRs. Median age was 8 years (2 weeks to 18 years), 41 patients
      (42%) were less than 5 years, and 16 were infants (17%). Etiology was congenital
      in 65 patients (67%), rheumatic in 27 (28%), and endocarditis in 5 (5%).
      Regurgitation was the predominant lesion in 67 patients (69%), stenosis in 23
      (24%), and mixed in 7 (7%) patients. Mechanical valves (ball, n=11; or bileaflet
      disc, n=66) and xenografts (porcine, n=14; bovine, n=2) were used in 93 initial
      MVR patients. Since 2002, 5 children have undergone Ross MVR with a pulmonary
      autograft in 3 and an aortic homograft in 2. RESULTS: Hospital mortality was 6%
      (6 of 97). There were 23 late deaths and 5 patients have required cardiac
      transplantation. Thirty-five year actuarial survival was 71%. Age less than 2
      years, MVR prior to 1980, atrioventricular septal defect, univentricular heart,
      and additional left side obstructions were significant predictors of death. Mean
      follow-up was 12.8+/-10.1 years (range, 2 months to 38 years). Seventeen patients
      with mechanical valves experienced systemic emboli in 9 (10%), valve thrombosis
      in 5 (6%), and bleeding requiring transfusion in 3 (3%) patients. Thirty-two
      patients required reoperations (35%) from 3 months to 14 years (mean, 6.5+/-4.4
      years) after initial MVR. Actuarial freedom from reoperation at 35 years was 63%.
      Variables associated with mitral re-replacement were younger age, small weight,
      valve diameter less than 23 mm, MVR prior to 1980, and type of implanted valves
      (xenograft, single-leaflet disk, ball-caged, or human valves). CONCLUSIONS:
      Pediatric MVR can be performed with low initial mortality but should be reserved
      for medical and reconstruction failure because reoperation, valve-related
      complications, and late mortality are high. Bileaflet prostheses larger than 23
      mm have the lowest reoperation risk. Ross MVR may offer select patients a durable
      tissue valve without lifelong anticoagulation and its associated complications.

PMID- 22153052
TI  - Task-dependent spatial distribution of neural activation pattern in human rectus
      femoris muscle.
AB  - Compartmentalization of skeletal muscle by multiple motor nerve branches, named
      as neuromuscular compartment (NMC), has been demonstrated in animals as well as
      humans. While different functional roles among individual NMCs were reported in
      the animal studies, no studies have clarified the region-specific functional role
      within a muscle related with NMCs arrangement in human skeletal muscle. It was
      reported that the rectus femoris (RF) muscle is innervated by two nerve branches
      attached at proximal and distal parts of the muscle. The purpose of the present
      study is to clarify the possible region-specific functional role in the human RF
      muscle. Multi-channel surface electromyography (SEMG) were recorded from the RF
      muscle by using 128 electrodes during two different submaximal isometric
      contractions that the muscle contributes, i.e. isometric knee extension and hip
      flexion, at 20%, 40%, 60% and 80% of maximal voluntary contraction (MVC). Results
      indicated that the central locus activation for the amplitude map of SEMG during
      hip flexion located at more proximal region compared with that during knee
      extension. Significant higher normalized root mean square (RMS) values were
      observed at the proximal region during the hip flexion in comparison to those at
      middle and distal regions at 60% and 80% of MVC (p<0.05). In while, significant
      higher normalized RMS values were demonstrated at the distal region comparing
      with that at the proximal region at 80% of MVC (p<0.05). The results of the
      present study suggest possible region-specific functional role in the human RF
      muscle.

PMID- 22153053
TI  - Refined carbohydrate intake in relation to non-verbal intelligence among Tehrani
      schoolchildren.
AB  - OBJECTIVE: Nutrition has long been considered one of the most important
      environmental factors affecting human intelligence. Although carbohydrates are
      the most widely studied nutrient for their possible effects on cognition, limited
      data are available linking usual refined carbohydrate intake and intelligence.
      The present study was conducted to examine the relationship between long-term
      refined carbohydrate intake and non-verbal intelligence among schoolchildren.
      DESIGN: Cross-sectional study. SETTING: Tehran, Iran. SUBJECTS: In this cross
      sectional study, 245 students aged 6-7 years were selected from 129 elementary
      schools in two western regions of Tehran. Anthropometric measurements were
      carried out. Non-verbal intelligence and refined carbohydrate consumption were
      determined using Raven's Standard Progressive Matrices test and a modified sixty
      seven-item FFQ, respectively. Data about potential confounding variables were
      collected. Linear regression analysis was applied to examine the relationship
      between non-verbal intelligence scores and refined carbohydrate consumption.
      RESULTS: Individuals in top tertile of refined carbohydrate intake had lower mean
      non-verbal intelligence scores in the crude model (P < 0.038). This association
      remained significant after controlling for age, gender, birth date, birth order
      and breast-feeding pattern (P = 0.045). However, further adjustments for mother's
      age, mother's education, father's education, parental occupation and BMI made the
      association statistically non-significant. We found a significant inverse
      association between refined carbohydrate consumption and non-verbal intelligence
      scores in regression models (beta = -11.359, P < 0.001). This relationship
      remained significant in multivariate analysis after controlling for potential
      confounders (beta = -8.495, P = 0.038). CONCLUSIONS: The study provides evidence
      indicating an inverse relationship between refined carbohydrate consumption and
      non-verbal intelligence among Tehrani children aged 6-7 years. Prospective
      studies are needed to confirm our findings.

PMID- 22153054
TI  - The effects of simulation-based resuscitation training on nurses' self-efficacy
      and satisfaction.
AB  - BACKGROUND: Nurses are often the first responders in clinical emergencies that
      require effective training to ensure high-quality resuscitation and patient
      safety. The aim of the study was to evaluate the efficacy of simulation-based
      resuscitation training by assessing two different training modalities (computer
      based simulation versus mannequin-based simulation) with practicing nurses.
      METHOD: The study used a comparative study design with random assignment to two
      simulation-based training modalities. A total of 38 nurses participated in the
      study: 18 nurses with computer-based simulation, and 20 nurses with mannequin
      based simulation. Participants rated their self-efficacy and satisfaction after
      participating in a simulated scenario involving managing a cardiac arrest
      patient. RESULTS: On a 10-point scale, the participants' overall self-efficacy
      rating was 6.50 (SD=1.66), and satisfaction rating was 7.53 (SD=1.20) for both
      groups. There were no significant differences between the groups. The computer
      based simulation group had significant higher satisfaction ratings in 'Setting
      priorities for nursing intervention' and 'Implementing nursing skills as
      protocol' compared to the mannequin-based simulation group. Most nurses felt the
      simulation experience was useful for future performance in their workplace, but
      rated realism of simulation as unsatisfactory. CONCLUSION: The introduction of
      simulation-based resuscitation training as an active-learning format was
      positively embraced by nurses. Computer-based simulation might be beneficial for
      acquiring nursing skills and decision making skills in resuscitation. Further
      study is needed to verify the effects of simulation-based resuscitation training
      with more rigorous outcomes.

PMID- 22153055
TI  - Patients assessing students' assignments; making the patient experience real.
AB  - The care of patients with inflammatory bowel disease (IBD) frequently falls short
      of the highest standards. This is noted in several publications, including
      national standards, despite nursing students being taught the importance of
      listening to and understanding patients. Teaching staff at the University of
      Glasgow primarily responsible for teaching third year undergraduate nursing
      students undertook a radical rethink of the planning, delivery and assessment of
      lectures on IBD. The subject had previously been delivered in a modified lecture
      format. Although the topic could be included in the end-of-year exams, there was
      little evidence to show whether this traditional teaching method had any effect
      on students' clinical practice. In a novel approach to learning and assessment,
      students were invited to research and produce an information leaflet for newly
      diagnosed patients with IBD. The leaflets were then assessed and grades awarded
      by an expert panel of patients and carers. Such enquiry based learning (EBL)
      intended to demonstrate in practice, the key role patients can play in both
      undergraduate nurse education and in service planning and delivery in the
      National Health Service (NHS). The panel found the exercise both interesting and
      insightful, while the students reported being invigorated and felt the expert
      assessment meant they were forced to achieve a higher level of work.

PMID- 22153056
TI  - Knowledge, attitudes and beliefs about tobacco use after an educative
      intervention in health sciences' students.
AB  - PURPOSE: To examine the effectiveness of a tobacco control course on the
      improvement of knowledge, attitudes and beliefs about smoking among health
      sciences' students. METHODS: This was a quasi-experimental study of community
      intervention carried out during the years 2005-2008, at 2 university health
      science centres in northwest Spain. A total of 290 students on the intervention
      and 256 on the control campus took part in the study. The intervention consisted
      of a course on the prevention and control of tobacco use offered only on the
      intervention campus. Data were collected before the intervention and 6 months
      afterwards. RESULTS: After the course, significant differences between groups
      were observed in the improvement of knowledge, attitudes and perceived ability to
      act in tobacco control. CONCLUSIONS: The introduction of training concerning
      smoking through active methodologies had a positive impact on the knowledge,
      attitudes and beliefs about tobacco of students.

PMID- 22153057
TI  - User involvement in health and social care education: a concept analysis.
AB  - This paper presents an evaluative discussion of the literature, and findings from
      a concept analysis which explores user involvement in the context of health and
      social care higher education in the United Kingdom. User involvement is
      increasingly a requirement in higher education and the purpose of the concept
      analysis was to clarify and elucidate the meaning and nature of the concept.
      Walker and Avant's (2005) eight step framework for concept analysis was used to
      provide understanding of the underlying attributes and a model for critique and
      meaningful evaluation and research. A structured search and discussion of
      contemporary literature was undertaken. A model case is identified along with
      antecedents, critical attributes and consequences. The complexities of
      involvement are delineated with a recommendation for robust research that
      explores the benefits of involvement.

PMID- 22153059
TI  - Tree nut phytochemicals: composition, antioxidant capacity, bioactivity, impact
      factors. A systematic review of almonds, Brazils, cashews, hazelnuts, macadamias,
      pecans, pine nuts, pistachios and walnuts.
AB  - Tree nuts contain an array of phytochemicals including carotenoids, phenolic
      acids, phytosterols and polyphenolic compounds such as flavonoids,
      proanthocyanidins (PAC) and stilbenes, all of which are included in nutrient
      databases, as well as phytates, sphingolipids, alkylphenols and lignans, which
      are not. The phytochemical content of tree nuts can vary considerably by nut
      type, genotype, pre- and post-harvest conditions, as well as storage conditions.
      Genotype affects phenolic acids, flavonoids, stilbenes and phytosterols, but data
      are lacking for many other phytochemical classes. During the roasting process,
      tree nut isoflavones, flavanols and flavonols were found to be more resistant to
      heat than the anthocyanins, PAC and trans-resveratrol. The choice of solvents
      used for extracting polyphenols and phytosterols significantly affects their
      quantification, and studies validating these methods for tree nut phytochemicals
      are lacking. The phytochemicals found in tree nuts have been associated with
      antioxidant, anti-inflammatory, anti-proliferative, antiviral, chemopreventive
      and hypocholesterolaemic actions, all of which are known to affect the initiation
      and progression of several pathogenic processes. While tree nut phytochemicals
      are bioaccessible and bioavailable in humans, the number of intervention trials
      conducted to date is limited. The objectives of the present review are to
      summarise tree nut: (1) phytochemicals; (2) phytochemical content included in
      nutrient databases and current publications; (3) phytochemicals affected by pre-
      and post-harvest conditions and analytical methodology; and (4) bioactivity and
      health benefits in humans.

PMID- 22153058
TI  - Forensically informative nucleotide sequencing (FINS) for the authentication of
      Chinese medicinal materials.
AB  - Chinese medicinal materials may be authenticated by molecular identification. As
      a definitive approach to molecular identification of medicinal materials,
      forensically informative nucleotide sequencing (FINS) comprises four steps,
      namely (1) DNA extraction from biological samples, (2) selection and
      amplification of a specific DNA fragment, (3) determination of the sequence of
      the amplified DNA fragment and (4) cladistic analysis of the sample DNA sequence
      against a DNA database. Success of the FINS identification depends on the
      selection of DNA region and reference species. This article describes the
      techniques and applications of FINS for authenticating Chinese medicinal
      materials.

PMID- 22153060
TI  - The effect of dietary methionine and white tea on oxidative status of gilthead
      sea bream (Sparus aurata).
AB  - Free radicals are continuously generated during an organism's lifetime. In order
      to understand the involvement in the oxidative status of fish, methionine and
      white tea were assayed as antioxidant supplements in diets for gilthead sea bream
      (Sparus aurata). For the purpose of this study, four isonitrogenous and
      isolipidic diets were formulated to contain 45 % of protein and 18 % lipid and
      0.3 % methionine (Met diet), 2.9 % white tea dry leaves (Tea diet) and 2.9 % of
      white tea dry leaves + 0.3 % methionine (Tea + Met diet). An unsupplemented diet
      was used as the control. Key enzymatic antioxidant defences, superoxide dismutase
      (SOD) isoenzyme profile, total, reduced and oxidised glutathione and oxidative
      damage markers were determined. The results showed that dietary methionine
      supplementation increased liver SOD activity, while white tea induced higher
      hepatic catalase activity. Dietary white tea induced a notable increase in Mn-SOD
      isoenzyme. This is the first study to provide evidence that dietary tea inclusion
      in fish feeding could be an important source of Mn with metabolic repercussions
      on antioxidant mechanisms.

PMID- 22153061
TI  - [New developments in ultrasound imaging for chronic liver diseases: from anatomic
      imaging to structural and functional imaging].
AB  - Conventional US imaging is playing a key role for the diagnosis and the
      therapeutic management of chronic liver diseases. Nevertheless, conventional US
      imaging is facing many limitations: operator-dependency, subjective assessment,
      variable detectability of nodules depending on accessibility to the US beam and
      spontaneous contrast to surrounding normal parenchyma, limited characterization
      capabilities. Conventional US imaging is taking advantage of major technological
      improvements including contrast-enhanced US (CEUS), elastography and volume and
      fusion imaging techniques. CEUS allows real-time detection of contrast
      enhancement and improves identification of the hypervascular pattern, major
      diagnostic criteria of hepatocellular carcinoma. Its kinetics is different from
      those of benign lesions (regenerative nodules, hemangioma...). CEUS is an
      excellent technique for focal liver lesion characterization (lesion detected
      previously at either conventional US or any imaging modality) while its
      performance remains limited for HCC detection. US contrast agent tolerance is
      excellent is routine clinical practise with no contraindication related to liver
      or renal dysfunction. US elastography is a non invasive technique that allows
      detection and quantification of liver fibrosis and is extending its application
      toward characterization of focal liver diseases. Volumetric and fusion imaging
      should improve the therapeutic management of malignant liver lesions and
      particularly percutaneous guidance of thermo-ablation procedures.

PMID- 22153063
TI  - Interdisciplinary graduate education: a case study.

PMID- 22153062
TI  - [Inflammatory lesions of the face due to Trichophyton mentagrophytes].

PMID- 22153064
TI  - Virus hunters: catching bugs in the field.
AB  - Densely populated areas in rural China require constant vigilance and state-of
      the-art technology to stop new pandemics in their tracks. Hurdles are not only
      scientific in some parts of the developing world.

PMID- 22153065
TI  - Bridging innate and adaptive immunity.
AB  - The Nobel Prize in Physiology or Medicine for 2011 to Jules Hoffmann, Bruce
      Beutler, and the late Ralph Steinman recognizes accomplishments in understanding
      and unifying the two strands of immunology, the evolutionarily ancient innate
      immune response and modern adaptive immunity.

PMID- 22153066
TI  - Lock and key to transcription: sigma-DNA interaction.
AB  - How does RNA polymerase recognize a promoter in duplex DNA? How are the DNA
      strands pried apart to enable RNA synthesis? A crystal structure by Feklistov and
      Darst unexpectedly reveals that these two processes are interconnected.

PMID- 22153067
TI  - A partner evokes latent differences between Hox proteins.
AB  - Hox transcription factors bind highly related DNA sequences in vitro, yet they
      regulate different genes and play distinct roles in anterior-posterior patterning
      in animals. Slattery et al. report that a common cofactor, Exd, accentuates
      latent sequence specificities of all eight Hox proteins and directs binding to
      relevant sites across the genome.

PMID- 22153068
TI  - Tankyrase loses its grip on SH3BP2 in cherubism.
AB  - Cherubism, a case of bone remodeling gone haywire, is associated with mutations
      in the adaptor protein SH3BP2. Two papers in this issue of Cell (Guettler et al.
      and Levaot et al.) demonstrate that these mutations disrupt the interaction
      between SH3BP2 and Tankyrase and describe rules for substrate recognition by this
      poly(ADP-ribose) polymerase. Establishing such rules paves the way to identifying
      all Tankyrase-regulated pathways in cells.

PMID- 22153069
TI  - Samurai sword sets spindle size.
AB  - Although the parts list is nearly complete for many cellular structures,
      mechanisms that control their size remain poorly understood. Loughlin and
      colleagues now show that phosphorylation of a single residue of katanin, a
      microtubule-severing protein, largely accounts for the difference in spindle
      length between two closely related frogs.

PMID- 22153070
TI  - Weaving the web of ER tubules.
AB  - How is the characteristic shape of an organelle generated? Recent work has
      provided insight into how the tubular network of the endoplasmic reticulum (ER)
      is formed. The tubules themselves are shaped by the reticulons and DP1/Yop1p,
      whereas their fusion into a network is brought about by membrane-bound GTPases
      that include the atlastins, Sey1p, and RHD3.

PMID- 22153071
TI  - An HNF4alpha-miRNA inflammatory feedback circuit regulates hepatocellular
      oncogenesis.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) is essential for liver development
      and hepatocyte function. Here, we show that transient inhibition of HNF4alpha
      initiates hepatocellular transformation through a microRNA-inflammatory feedback
      loop circuit consisting of miR-124, IL6R, STAT3, miR-24, and miR-629. Moreover,
      we show that, once this circuit is activated, it maintains suppression of
      HNF4alpha and sustains oncogenesis. Systemic administration of miR-124, which
      modulates inflammatory signaling, prevents and suppresses hepatocellular
      carcinogenesis by inducing tumor-specific apoptosis without toxic side effects.
      As we also show that this HNF4alpha circuit is perturbed in human hepatocellular
      carcinomas, our data raise the possibility that manipulation of this microRNA
      feedback-inflammatory loop has therapeutic potential for treating liver cancer.

PMID- 22153072
TI  - Cofactor binding evokes latent differences in DNA binding specificity between Hox
      proteins.
AB  - Members of transcription factor families typically have similar DNA binding
      specificities yet execute unique functions in vivo. Transcription factors often
      bind DNA as multiprotein complexes, raising the possibility that complex
      formation might modify their DNA binding specificities. To test this hypothesis,
      we developed an experimental and computational platform, SELEX-seq, that can be
      used to determine the relative affinities to any DNA sequence for any
      transcription factor complex. Applying this method to all eight Drosophila Hox
      proteins, we show that they obtain novel recognition properties when they bind
      DNA with the dimeric cofactor Extradenticle-Homothorax (Exd). Exd-Hox
      specificities group into three main classes that obey Hox gene collinearity rules
      and DNA structure predictions suggest that anterior and posterior Hox proteins
      prefer DNA sequences with distinct minor groove topographies. Together, these
      data suggest that emergent DNA recognition properties revealed by interactions
      with cofactors contribute to transcription factor specificities in vivo.

PMID- 22153073
TI  - Polycomb-repressed genes have permissive enhancers that initiate reprogramming.
AB  - Key regulatory genes, suppressed by Polycomb and H3K27me3, become active during
      normal differentiation and induced reprogramming. Using the well-characterized
      enhancer/promoter pair of MYOD1 as a model, we have identified a critical role
      for enhancers in reprogramming. We observed an unexpected nucleosome-depleted
      region (NDR) at the H3K4me1-enriched enhancer at which transcriptional regulators
      initially bind, leading to subsequent changes in the chromatin at the cognate
      promoter. Exogenous Myod1 activates its own transcription by binding first at the
      enhancer, leading to an NDR and transcription-permissive chromatin at the
      associated MYOD1 promoter. Exogenous OCT4 also binds first to the permissive
      MYOD1 enhancer but has a different effect on the cognate promoter, where the
      monovalent H3K27me3 marks are converted to the bivalent state characteristic of
      stem cells. Genome-wide, a high percentage of Polycomb targets are associated
      with putative enhancers in permissive states, suggesting that they may provide a
      widespread avenue for the initiation of cell-fate reprogramming.

PMID- 22153074
TI  - Selective ribosome profiling reveals the cotranslational chaperone action of
      trigger factor in vivo.
AB  - As nascent polypeptides exit ribosomes, they are engaged by a series of
      processing, targeting, and folding factors. Here, we present a selective ribosome
      profiling strategy that enables global monitoring of when these factors engage
      polypeptides in the complex cellular environment. Studies of the Escherichia coli
      chaperone trigger factor (TF) reveal that, though TF can interact with many
      polypeptides, beta-barrel outer-membrane proteins are the most prominent
      substrates. Loss of TF leads to broad outer-membrane defects and premature,
      cotranslational protein translocation. Whereas in vitro studies suggested that TF
      is prebound to ribosomes waiting for polypeptides to emerge from the exit
      channel, we find that in vivo TF engages ribosomes only after ~100 amino acids
      are translated. Moreover, excess TF interferes with cotranslational removal of
      the N-terminal formyl methionine. Our studies support a triaging model in which
      proper protein biogenesis relies on the fine-tuned, sequential engagement of
      processing, targeting, and folding factors.

PMID- 22153075
TI  - The STARD9/Kif16a kinesin associates with mitotic microtubules and regulates
      spindle pole assembly.
AB  - During cell division, cells form the microtubule-based mitotic spindle, a highly
      specialized and dynamic structure that mediates proper chromosome transmission to
      daughter cells. Cancer cells can show perturbed mitotic spindles and an approach
      in cancer treatment has been to trigger cell killing by targeting microtubule
      dynamics or spindle assembly. To identify and characterize proteins necessary for
      spindle assembly, and potential antimitotic targets, we performed a proteomic and
      genetic analysis of 592 mitotic microtubule copurifying proteins (MMCPs).
      Screening for regulators that affect both mitosis and apoptosis, we report the
      identification and characterization of STARD9, a kinesin-3 family member, which
      localizes to centrosomes and stabilizes the pericentriolar material (PCM). STARD9
      depleted cells have fragmented PCM, form multipolar spindles, activate the
      spindle assembly checkpoint (SAC), arrest in mitosis, and undergo apoptosis.
      Interestingly, STARD9-depletion synergizes with the chemotherapeutic agent taxol
      to increase mitotic death, demonstrating that STARD9 is a mitotic kinesin and a
      potential antimitotic target.

PMID- 22153076
TI  - Loss of Tankyrase-mediated destruction of 3BP2 is the underlying pathogenic
      mechanism of cherubism.
AB  - Cherubism is an autosomal-dominant syndrome characterized by inflammatory
      destructive bony lesions resulting in symmetrical deformities of the facial
      bones. Cherubism is caused by mutations in Sh3bp2, the gene that encodes the
      adaptor protein 3BP2. Most identified mutations in 3BP2 lie within the peptide
      sequence RSPPDG. A mouse model of cherubism develops hyperactive bone-remodeling
      osteoclasts and systemic inflammation characterized by expansion of the
      myelomonocytic lineage. The mechanism by which cherubism mutations alter 3BP2
      function has remained obscure. Here we show that Tankyrase, a member of the
      poly(ADP-ribose)polymerase (PARP) family, regulates 3BP2 stability through ADP
      ribosylation and subsequent ubiquitylation by the E3-ubiquitin ligase RNF146 in
      osteoclasts. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein
      destruction, which results in its stabilization and subsequent hyperactivation of
      the SRC, SYK, and VAV signaling pathways.

PMID- 22153077
TI  - Structural basis and sequence rules for substrate recognition by Tankyrase
      explain the basis for cherubism disease.
AB  - The poly(ADP-ribose)polymerases Tankyrase 1/2 (TNKS/TNKS2) catalyze the covalent
      linkage of ADP-ribose polymer chains onto target proteins, regulating their
      ubiquitylation, stability, and function. Dysregulation of substrate recognition
      by Tankyrases underlies the human disease cherubism. Tankyrases recruit specific
      motifs (often called RxxPDG "hexapeptides") in their substrates via an N-terminal
      region of ankyrin repeats. These ankyrin repeats form five domains termed ankyrin
      repeat clusters (ARCs), each predicted to bind substrate. Here we report crystal
      structures of a representative ARC of TNKS2 bound to targeting peptides from six
      substrates. Using a solution-based peptide library screen, we derive a rule-based
      consensus for Tankyrase substrates common to four functionally conserved ARCs.
      This 8-residue consensus allows us to rationalize all known Tankyrase substrates
      and explains the basis for cherubism-causing mutations in the Tankyrase substrate
      3BP2. Structural and sequence information allows us to also predict and validate
      other Tankyrase targets, including Disc1, Striatin, Fat4, RAD54, BCR, and
      MERIT40.

PMID- 22153078
TI  - Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic
      cells.
AB  - Antigen (Ag) crosspresentation by dendritic cells (DCs) involves the presentation
      of internalized Ags on MHC class I molecules to initiate CD8+ T cell-mediated
      immunity in response to certain pathogens and tumor cells. Here, we identify the
      SNARE Sec22b as a specific regulator of Ag crosspresentation. Sec22b localizes to
      the ER-Golgi intermediate compartment (ERGIC) and pairs to the plasma membrane
      SNARE syntaxin 4, which is present in phagosomes (Phgs). Depletion of Sec22b
      inhibits the recruitment of ER-resident proteins to Phgs and to the vacuole
      containing the Toxoplasma gondii parasite. In Sec22b-deficient DCs,
      crosspresentation is compromised after Ag phagocytosis or endocytosis and after
      invasion by T. gondii. Sec22b silencing inhibited Ag export to the cytosol and
      increased phagosomal degradation by accelerating lysosomal recruitment. Our
      findings provide insight into an intracellular traffic pathway required for
      crosspresentation and show that Sec22b-dependent recruitment of ER proteins to
      Phgs critically influences phagosomal functions in DCs.

PMID- 22153079
TI  - Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic
      plasticity and memory storage.
AB  - The cytoplasmic polyadenylation element-binding protein 3 (CPEB3), a regulator of
      local protein synthesis, is the mouse homolog of ApCPEB, a functional prion
      protein in Aplysia. Here, we provide evidence that CPEB3 is activated by
      Neuralized1, an E3 ubiquitin ligase. In hippocampal cultures, CPEB3 activated by
      Neuralized1-mediated ubiquitination leads both to the growth of new dendritic
      spines and to an increase of the GluA1 and GluA2 subunits of AMPA receptors, two
      CPEB3 targets essential for synaptic plasticity. Conditional overexpression of
      Neuralized1 similarly increases GluA1 and GluA2 and the number of spines and
      functional synapses in the hippocampus and is reflected in enhanced hippocampal
      dependent memory and synaptic plasticity. By contrast, inhibition of Neuralized1
      reduces GluA1 and GluA2 levels and impairs hippocampal-dependent memory and
      synaptic plasticity. These results suggest a model whereby Neuralized1-dependent
      ubiquitination facilitates hippocampal plasticity and hippocampal-dependent
      memory storage by modulating the activity of CPEB3 and CPEB3-dependent protein
      synthesis and synapse formation.

PMID- 22153080
TI  - Suppression of PKR promotes network excitability and enhanced cognition by
      interferon-gamma-mediated disinhibition.
AB  - The double-stranded RNA-activated protein kinase (PKR) was originally identified
      as a sensor of virus infection, but its function in the brain remains unknown.
      Here, we report that the lack of PKR enhances learning and memory in several
      behavioral tasks while increasing network excitability. In addition, loss of PKR
      increases the late phase of long-lasting synaptic potentiation (L-LTP) in
      hippocampal slices. These effects are caused by an interferon-gamma (IFN-gamma)
      mediated selective reduction in GABAergic synaptic action. Together, our results
      reveal that PKR finely tunes the network activity that must be maintained while
      storing a given episode during learning. Because PKR activity is altered in
      several neurological disorders, this kinase presents a promising new target for
      the treatment of cognitive dysfunction. As a first step in this direction, we
      show that a selective PKR inhibitor replicates the Pkr(-/-) phenotype in WT mice,
      enhancing long-term memory storage and L-LTP.

PMID- 22153081
TI  - Katanin contributes to interspecies spindle length scaling in Xenopus.
AB  - Bipolar spindles must separate chromosomes by the appropriate distance during
      cell division, but mechanisms determining spindle length are poorly understood.
      Based on a 2D model of meiotic spindle assembly, we predicted that higher
      localized microtubule (MT) depolymerization rates could generate the shorter
      spindles observed in egg extracts of X. tropicalis compared to X. laevis. We
      found that katanin-dependent MT severing was increased in X. tropicalis, which,
      unlike X. laevis, lacks an inhibitory phosphorylation site in the katanin p60
      catalytic subunit. Katanin inhibition lengthened spindles in both species. In X.
      tropicalis, k-fiber MT bundles that connect to chromosomes at their kinetochores
      extended through spindle poles, disrupting them. In both X. tropicalis extracts
      and the spindle simulation, a balance between k-fiber number and MT
      depolymerization is required to maintain spindle morphology. Thus, mechanisms
      have evolved in different species to scale spindle size and coordinate regulation
      of multiple MT populations in order to generate a robust steady-state structure.

PMID- 22153082
TI  - Comprehensive genome-wide protein-DNA interactions detected at single-nucleotide
      resolution.
AB  - Chromatin immunoprecipitation (ChIP-chip and ChIP-seq) assays identify where
      proteins bind throughout a genome. However, DNA contamination and DNA
      fragmentation heterogeneity produce false positives (erroneous calls) and
      imprecision in mapping. Consequently, stringent data filtering produces false
      negatives (missed calls). Here we describe ChIP-exo, where an exonuclease trims
      ChIP DNA to a precise distance from the crosslinking site. Bound locations are
      detectable as peak pairs by deep sequencing. Contaminating DNA is degraded or
      fails to form complementary peak pairs. With the single bp accuracy provided by
      ChIP-exo, we show an unprecedented view into genome-wide binding of the yeast
      transcription factors Reb1, Gal4, Phd1, Rap1, and human CTCF. Each of these
      factors was chosen to address potential limitations of ChIP-exo. We found that
      binding sites become unambiguous and reveal diverse tendencies governing in vivo
      DNA-binding specificity that include sequence variants, functionally distinct
      motifs, motif clustering, secondary interactions, and combinatorial modules
      within a compound motif.

PMID- 22153084
TI  - Re: Appendectomy in pregnancy: evaluation of the risks of a negative
      appendectomy.

PMID- 22153083
TI  - SnapShot: retinoic acid signaling.

PMID- 22153085
TI  - Current management practice of breast borderline lesions--need for further
      research and guidelines.
AB  - BACKGROUND: Breast borderline lesions are usually diagnosed on needle biopsies of
      imaging abnormalities. The natural history of these lesions is unclear, and the
      literature is divided on appropriate management. It was hypothesized that
      management varies among surgeons and may be associated with surgeon and practice
      characteristics. METHODS: A survey of 477 members of the American Society of
      Breast Surgeons was completed. Results were analyzed according to various surgeon
      and practice characteristics. RESULTS: Most respondents recommended routine
      excision for atypical ductal and lobular hyperplasia. Excision of radial scars
      and papillomas was much more variable, with only 50% recommending routine
      excision. Results differed by surgical dedication to breast surgery and
      fellowship training. Management of atypical ductal or lobular hyperplasia found
      at the margin varied significantly. The lack of a routine tumor board, low breast
      case volume, and low percentage of breast cases were associated with routine
      excision in these cases. CONCLUSIONS: Breast borderline lesions pose a clinical
      dilemma, with practice varying greatly among surgeons.

PMID- 22153086
TI  - A 60-year literature review of stump appendicitis: the need for a critical view.
AB  - BACKGROUND: Stump appendicitis is an underreported and poorly defined condition.
      It is the development of obstruction and inflammation of the residual appendix
      after appendectomy. This is a review of the basic clinical, pathological, and
      surgical significance of stump appendicitis, and the "critical view" required for
      prevention. DATA SOURCES: PubMed MEDLINE search was performed using terms "stump
      appendicitis" and "retained appendix" to obtain reported cases of stump
      appendicitis. Sixty-one cases were identified. Each case was charted based on 14
      variables. Data were analyzed. CONCLUSIONS: Stump appendicitis warrants early
      detection. Patients can present with abdominal pain, nausea, and vomiting. A
      prior history of appendectomy can delay the diagnosis. A diagnosis can be made
      with an abdominal ultrasound or computed tomography scan. If treated early,
      laparoscopic or open completion appendectomy can be performed. If diagnosis is
      delayed and perforation is found, extensive resection is often required. A
      "critical view," as described in this article, is key for prevention.

PMID- 22153087
TI  - Preventing seroma formation after axillary dissection for breast cancer: a
      randomized clinical trial.
AB  - BACKGROUND: Seroma formation after axillary dissection remains the most common
      early sequel to breast cancer surgery. Different surgical approaches have been
      performed to reduce seroma collection. Therefore, we aimed to assess the outcome
      of patients operated on using an ultrasound scalpel according to a standardized
      operative technique before accepting it as a routine procedure. METHODS: A
      randomized controlled trial was designed to compare the outcome of patients
      undergoing breast surgery and axillary dissection using either standard scalpel
      blades, scissors, ligations, and electrocautery or the ultrasound scalpel only.
      Each arm of the trial consisted of 30 patients. RESULTS: A statistically
      significant benefit in terms of axillary and chest wall drainage volume, the
      number of axilla seromas, intraoperative bleeding, and hospitalization stay was
      recorded in the harmonic scalpel group. No significant differences were found
      between the 2 groups in terms of operative time. Finally, no postoperative
      hematoma, wound infections, and chest wall seroma were observed. CONCLUSIONS: The
      use of the harmonic scalpel was shown to reduce the magnitude of seromas in
      axilla and hospitalization stay. The harmonic scalpel can be used alone in
      axillary dissection with a safe and effective hemostasis. Our results must be
      confirmed by larger series.

PMID- 22153088
TI  - Response to: Do pregnant women have improved outcomes after traumatic brain
      injury.

PMID- 22153090
TI  - Single versus double femtosecond laser pass for incomplete laser in situ
      keratomileusis flap in contralateral eyes: visual and optical outcomes.
AB  - PURPOSE: To evaluate visual acuity, refractive outcomes, and anterior corneal
      higher-order aberrations (HOAs) after myopic laser in situ keratomileusis (LASIK)
      with uneventful single femtosecond laser pass versus double pass performed for
      intraoperative suction loss. SETTING: Private refractive surgery center,
      Valencia, Spain. DESIGN: Cohort study. METHODS: After the LASIK flap was created
      with a single pass of an Intralase femtosecond laser in 1 eye and a double pass
      in the fellow eye, the ablation was performed with a Visx S2 laser. At 12 months,
      the refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuities,
      and anterior corneal HOAs were measured with 4.0 mm and 6.0 mm pupils. RESULTS:
      The study enrolled 42 eyes (21 patients). Twelve months postoperatively, there
      were no statistically significant differences in any parameter studied including
      residual spherical equivalent (mean -0.05 diopter [D] +/- 0.25 [SD] single pass; 
      0.03 +/- 0.19 D double pass; P=.75), UDVA (mean 0.008 +/- 0.057 logMAR single
      pass; 0.011 +/- 0.046 logMAR double pass; P=.89), CDVA (mean -0.010 +/- 0.040
      logMAR single pass; -0.007 +/- 0.037 logMAR double pass; P=.74), or anterior
      corneal HOAs. No eye lost 1 line of CDVA. CONCLUSIONS: Visual acuity, refractive
      outcomes, and anterior corneal HOAs were comparable between eyes after uneventful
      femtosecond laser single pass or double pass after suction loss affecting the
      pupillary area. A new femtosecond laser pass performed immediately after
      incomplete flap due to intraoperative suction loss provided good visual and
      optical outcomes.

PMID- 22153091
TI  - Optical quality after myopic photorefractive keratectomy and laser in situ
      keratomileusis: comparison using a double-pass system.
AB  - PURPOSE: To use a double-pass system to compare the optical quality after
      photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) for
      mild to moderate myopia. SETTING: Universitat Politecnica de Catalunya, Terrassa,
      Barcelona Institute of Ocular Microsurgery, Barcelona, Spain. DESIGN: Comparative
      case series. METHODS: Optical quality was assessed with a clinical double-pass
      system preoperatively and 3 months after PRK or LASIK. The modulation transfer
      function (MTF), retinal image quality parameters (MTF cutoff frequency, Strehl
      ratio), and intraocular scattering (objective scatter index [OSI]) were
      calculated. RESULTS: This study evaluated 34 eyes that had PRK and 55 eyes that
      had LASIK. Both PRK and LASIK had a statistically significant impact on retinal
      image quality, although no significant differences between the techniques were
      observed. The MTF at 30 cycles per degree decreased by a factor of 1.50 in the
      PRK group and by a factor of 1.32 in the LASIK group. The MTF cutoff frequency
      decreased by a factor of 1.04 in the PRK group and by a factor of 1.06 in the
      LASIK group. The Strehl ratio decreased by a factor of 1.10 and 1.07,
      respectively. Photorefractive keratectomy and LASIK increased the objective
      scatter index by factors of 1.48 and 1.57, respectively. Significant correlations
      between the preoperative refraction and the OSI were found. CONCLUSIONS: Retinal
      image quality was similarly reduced with PRK and LASIK, with no significant
      differences between the 2 methods. Some PRK patients had a residual refractive
      error that might have been related to corneal-wound healing still present 3
      months postoperatively.

PMID- 22153092
TI  - Central vault after phakic intraocular lens implantation: correlation with
      anterior chamber depth, white-to-white distance, spherical equivalent, and
      patient age.
AB  - PURPOSE: To compare the central postoperative vault of a phakic intraocular lens
      (pIOL) to correct myopia, myopic astigmatism, and hyperopia and identify ocular
      and lens parameters that might predict the vault amount. SETTING: Fernandez-Vega
      Ophthalmological Institute, Oviedo, Spain. DESIGN: Cohort study. METHODS: Three
      months after implantation of Implantable Collamer Lens pIOLs to correct myopia,
      hyperopia, and myopic astigmatism, central vault was measured using optical
      coherence tomography. Patients were divided into groups according to the
      preoperative anterior chamber depth (ACD) to compare the effects of ACD, white-to
      white (WTW) distance, and lens diameter on postoperative pIOL vault. RESULTS:
      Hyperopic pIOLs had statistically significantly lower vault followed by myopic
      pIOLs and toric pIOLs, which had a higher mean value and narrower range (260 to
      860 MUm). Measured vaults had a positive correlation with preoperative ACD (r =
      .32, P<.001) and WTW (r = .29, P<.001) and a negative correlation with
      preoperative spherical equivalent (SE) (r = -0.21, P<.001) and patient age (r = 
      0.12, P=.025). Eyes with a vault of 250 MUm or less had a shallower ACD than eyes
      with a vault between 250 MUm and 750 MUm (mean difference -0.11 mm; P=.012) and
      those with a vault greater than 750 MUm (mean difference -0.25 mm; P<.001).
      CONCLUSIONS: Central vaulting was lower in hyperopic eyes. Current nomograms for
      pIOL diameter selection based on ACD and WTW might yield ideal vault and may have
      to be adjusted for older patients, shallower ACD, lower WTW, and lower SE.

PMID- 22153093
TI  - Refractive shift in pseudophakic eyes during the second decade of life.
AB  - PURPOSE: To evaluate the refractive shift in pseudophakic eyes of children after
      their 10th birthday. SETTING: Storm Eye Institute, Charleston, South Carolina,
      USA. DESIGN: Case series. METHODS: One eye of each patient with at least 2
      refractions at a minimum of a 1-year interval after the 10th birthday was
      analyzed. RESULTS: One hundred fourteen pseudophakic eyes (114 patients) were
      identified. The mean initial refraction was -0.65 diopter (D) +/- 2.27 (SD) and
      the mean final refraction, -1.78 +/- 2.82 D. The mean shift in refraction was 
      1.13 +/- 1.36 D; the mean shift in refraction per year was -0.30 +/- 0.38 D.
      Postoperative refraction could be predicted by regression analysis (P<.001).
      There was a myopic shift in refraction in 86.8% of eyes; 64.0% of eyes had up to
      a 0.50 D myopic shift per year. Age at the time of intraocular lens (IOL)
      implantation (before or after 10 years of age) did not influence the refractive
      shift in pseudophakic eyes of children after their 10th birthday. However, the
      refractive shift was significantly different between black patients and white
      patients (P=.006). In unilateral cases, 27 eyes had refraction data available for
      the fellow eye. The mean refractive shift per year was -0.19 D in the operated
      eye and -0.22 D in the fellow eye (P=.67). CONCLUSION: A myopic shift in
      refraction continued in children after 10 years of age, which has important
      implications for the use of multifocal IOLs in preteens and teenagers and for IOL
      power selection.

PMID- 22153094
TI  - Homeostatic response of intraocular pressure in the early period after sutureless
      phacoemulsification.
AB  - PURPOSE: To determine the homeostatic response of postoperative intraocular
      pressure (IOP) by analyzing postoperative IOP trends after sutureless
      phacoemulsification. SETTING: Asan Medical Center, Seoul, South Korea. DESIGN:
      Comparative case series. METHODS: Normotensive eyes were treated with sutureless
      phacoemulsification with in-the-bag posterior chamber IOL (PC IOL) implantation.
      The patients were randomly divided into 3 groups according to the intended
      immediate postoperative IOP as follows: Group 1, IOP less than 10 mm Hg; Group 2,
      IOP 10 to 21 mm Hg; Group 3, IOP over 21 mm Hg. The surgeon intentionally
      attempted supranormal, normal, or subnormal pressurization. The IOP was measured
      immediately after surgery and 2 hours, 4 hours, 1 day, 1 week, and 1 month
      postoperatively. RESULTS: Group 1 included 88 eyes (27.8%), Group 2 included 130
      eyes (41.2%), and Group 3 included 98 eyes (31.0%). The mean IOP immediately
      after surgery was 6.4 mm Hg +/- 2.0 (SD), 14.5 +/- 3.2 mm Hg, and 27.0 +/- 4.6 mm
      Hg, respectively, with significant differences between the 3 groups (P<.05).
      However, the IOP values were nearly normalized in the 3 groups 2 to 4 hours
      postoperatively. Twenty-eight eyes (8.9%) had an IOP lower than 5 mm Hg
      immediately after surgery in the absence of incision leakage. There were no
      postoperative complications related to hypotony. Thirty-one eyes (9.8%) had an
      IOP of at least 30 mm Hg immediately after surgery; the IOP normalized by 1 day
      postoperatively. CONCLUSION: In normal eyes that had uneventful sutureless
      phacoemulsification with in-the-bag PC IOL implantation, immediate postoperative
      high or low IOP did not affect the return to baseline levels.

PMID- 22153095
TI  - Lenticular meridional astigmatism secondary to iris mesectodermal leiomyoma.
AB  - A 61-year-old African American man presented with decreased vision of 2 months
      duration. Examination revealed a significant lenticular astigmatism and sectoral
      cataract as a result of an amelanotic iris lesion. Slitlamp optical coherence
      tomography (OCT) revealed angle crowding. An excisional biopsy was performed
      along with phacoemulsification in the right eye, with intraocular lens
      implantation for meridional lenticular astigmatism. Histopathology and
      histoimmunochemistry confirmed a diagnosis of uveal mesectodermal leiomyoma.
      Lenticular astigmatism may be a subtle sign of an anterior segment tumor.
      Anterior segment slitlamp OCT is an effective tool in diagnosing as well as
      monitoring small interval changes in these types of tumors.

PMID- 22153096
TI  - Brown discoloration of acrylic multifocal, monofocal, and blue light-filtering
      IOLs.

PMID- 22153097
TI  - Consultation section. Refractive surgical problem.

PMID- 22153106
TI  - Oval capsulorhexis and its advantages.

PMID- 22153107
TI  - Risk stratification and assessment in cataract surgery.

PMID- 22153110
TI  - Steroid depot injection versus postoperative steroid eyedrops to prevent
      inflammation and macular edema after cataract surgery.

PMID- 22153112
TI  - Prevention of post cataract-surgery cystoid macular edema with nepafenac.

PMID- 22153114
TI  - Assessing the value of simulator training on residency performance.

PMID- 22153116
TI  - Decade of Action for Road Safety 2011-2020.

PMID- 22153117
TI  - Comparative analysis of trends in paediatric trauma outcomes in New South Wales,
      Australia.
AB  - Paediatric trauma centres seek to optimise the care of injured children. Trends
      in state-wide paediatric care and outcomes have not been examined in detail in
      Australia. This study examines temporal trends in paediatric trauma outcomes and
      factors influencing survival and length of stay. A retrospective review was
      conducted using data from the NSW Trauma Registry during 2003-2008 for children
      aged 15 years and younger who were severely injured (injury severity score >15).
      To examine trauma outcomes descriptive statistics and multivariable logistic and
      linear regression were conducted. There were 1138 children severely injured. Two
      thirds were male. Road trauma and falls were the most common injury mechanisms
      and over one-third of incidents occurred in the home. Forty-eight percent of
      violence-related injuries were experienced by infants aged less than 1 year. For
      the majority of children definitive care was provided at a paediatric trauma
      centre, but less than one-third of children were taken directly to a paediatric
      trauma centre post-injury. Children who received definitive treatment at a
      paediatric trauma centre had between 3 and 6 times higher odds of having a
      survival advantage than if treated at an adult trauma centre. The number of
      severe injury presentations to the 14 major trauma centres in NSW remains
      constant. It is possible that injury prevention measures are having a limited
      effect on severe injury in NSW. This research provides stimulus for change in the
      provision and co-ordination in the delivery of trauma care for injured children.

PMID- 22153118
TI  - Human cardioviruses, meningitis, and sudden infant death syndrome in children.
AB  - Cardioviruses cause myocarditis and encephalomyelitis in rodents; human
      cardioviruses have not been ascribed to any disease. We screened 6,854
      cerebrospinal fluid and 10 myocardium specimens from children and adults. A
      genotype 2 cardiovirus was detected from a child who died of sudden infant death
      syndrome, and 2 untypeable cardioviruses were detected from 2 children with
      meningitis.

PMID- 22153119
TI  - Novel approaches to the control of helminth parasites of livestock. Foreword.

PMID- 22153120
TI  - Differential immune response between fundic and pyloric abomasal regions upon
      experimental ovine infection with Haemonchus contortus.
AB  - The effect of experimental haemonchosis on the number of tissue eosinophils,
      plasma cells and lymphocyte subpopulations was evaluated in the fundic abomasal
      region, the pyloric abomasal region and the abomasal lymph node of Blackbelly
      lambs, which are resistant to infection, and Columbia lambs, which are
      susceptible to infection. An increase in the number of tissue eosinophils and
      CD4+ and WC1(+)gammadelta T-cells was observed in the pyloric abomasal region of
      Blackbelly lambs and correlated with lower worm burden and greater resistance to
      infection. Increases in IgA+ plasma cells from the pyloric abomasal region were
      observed in both infected groups, but there was no difference between the groups.
      Therefore, increases in IgA+ plasma cells did not explain the resistance
      observed. Infection caused a significant increase in tissue eosinophils in the
      abomasal lymph node of Blackbelly lambs and a decrease in the number of CD4+ T
      cells in lambs of both breeds. CD8+ T-cells and IgG+ and IgM+ plasma cells were
      not associated with either infection or resistance. In this work, clear
      differences were observed in the numbers of CD4+ and WC1(+)gammadelta T-cells,
      tissue eosinophils and IgA+ plasma cells between the abomasal regions studied.
      These differences indicate that the immunological response is not homogenous in
      all abomasal mucosa and that evaluating the response from a single abomasal
      region may not be representative of the cellular response across the abomasum.

PMID- 22153121
TI  - Salivary IgA: a suitable measure of immunity to gastrointestinal nematodes in
      sheep.
AB  - Infection with gastrointestinal nematodes (GIN) is a major constraint on the
      productivity of grazing livestock. The development of selection methods to
      quickly and accurately identify animals capable of developing an effective
      natural immunity to infection would contribute to the development of sustainable
      worm control programs. A carbohydrate larval surface antigen (CarLA), present on
      the infective-stage larvae (L3) of all trichostrongylid nematodes, is a target
      antigen for host antibody (Ab). The levels of various Ab isotypes in serum and/or
      saliva of field-grazed lambs were assessed by ELISA, and Ab titres compared with
      parasite faecal egg counts (FECs) and a range of animal productivity parameters.
      Levels of anti-CarLA IgA in saliva proved to be the most heritable (h(2)=0.3),
      and had the closest genetic correlation with FEC (r=-0.5). Those animals
      identified as having 'high levels' of anti-CarLA IgA typically have 20-30% lower
      FEC than animals with low or undetectable titres. Furthermore, animals with 'high
      levels' of anti-CarLA IgA tend to have improved growth rates post-weaning, and
      have no tendency for increased breech-soiling. The assay performed well
      regardless of parasite genera present on pasture. The saliva assay has a number
      of key practical advantages over the use of FEC for selection purposes: animals
      can be identified without a requirement to withhold anthelmintic treatment;
      sampling is rapid and easy and there is a significantly reduced barrier to
      adoption within the farming community. Measurement of anti-CarLA IgA in saliva by
      ELISA offers a practical, rapid and easy method of selecting for natural immunity
      to GIN in sheep.

PMID- 22153122
TI  - The strawberry: composition, nutritional quality, and impact on human health.
AB  - Strawberries are a common and important fruit in the Mediterranean diet because
      of their high content of essential nutrients and beneficial phytochemicals, which
      seem to have relevant biological activity in human health. Among these
      phytochemicals, anthocyanin and ellagitannins are the major antioxidant
      compounds. Although individual phytochemical constituents of strawberries have
      been studied for their biological activities, human intervention studies using
      whole fruits are still lacking. Here, the nutritional contribution and
      phytochemical composition of the strawberry are reviewed, as is the role played
      by the maturity, genotype, and storage effects on this fruit. Specific attention
      is focused on fruit absorption, metabolism, and the possible beneficial
      biological activity on human health.

PMID- 22153123
TI  - Radiation-induced platelet-endothelial cell interactions are mediated by P
      selectin and P-selectin glycoprotein ligand-1 in the colonic microcirculation.
AB  - BACKGROUND: Antiplatelet reagents have been reported to protect against
      intestinal damage associated with abdominal radiotherapy, but the mechanisms
      behind radiation-induced platelet-endothelium interactions are not known. We
      sought to define the adhesive mechanisms that regulate radiotherapy-induced
      platelet-endothelial cell interactions in the colon. METHODS: All mice except the
      controls were exposed to abdominal radiation with a single dose of 20 Gray. Mice
      were pretreated with an isotype-matched control antibody or a monoclonal antibody
      directed against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1).
      Platelet and leukocyte rolling and adhesion in the colon were determined by use
      of inverted intravital fluorescence microscopy 16 hours after radiation.
      Radiation-induced intestinal leakage of fluorescein isothiocyanate-conjugated
      dextran was examined in separate experiments. RESULTS: Immunoneutralization of P
      selectin decreased radiation-provoked platelet rolling by 87% and adhesion by
      63%. Moreover, inhibition of PSGL-1 decreased platelet rolling and adhesion by
      77% and 83%, respectively, in animals exposed to radiation. Similarly, inhibition
      of P-selectin and PSGL-1 decreased radiation-induced leukocyte rolling and
      adhesion by more than 84% and 90%, respectively, in the colon. In contrast,
      inhibition of P-selectin or PSGL-1 had no impact on radiation-induced intestinal
      leakage. In addition, systemic depletion of platelets and leukocytes did not
      affect intestinal barrier dysfunction in radiated animals. CONCLUSION: This study
      demonstrates that radiation-provoked platelet and leukocyte accumulation are
      mediated in part by P-selectin and PSGL-1. Radiation-induced gut leakage,
      however, is independent of accumulation of platelets and leukocytes in the
      intestinal microvasculature.

PMID- 22153124
TI  - Clinical risk assessment rating and all-cause mortality in secondary mental
      healthcare: the South London and Maudsley NHS Foundation Trust Biomedical
      Research Centre (SLAM BRC) Case Register.
AB  - BACKGROUND: Mental disorders are widely recognized to be associated with
      increased risk of all-cause mortality. However, the extent to which highest-risk
      groups for mortality overlap with those viewed with highest concern by mental
      health services is less clear. The aim of the study was to investigate clinical
      risk assessment ratings for suicide, violence and self-neglect in relation to all
      cause mortality among people receiving secondary mental healthcare. METHOD: A
      total of 9234 subjects over the age of 15 years were identified from the South
      London and Maudsley Biomedical Research Centre Case Register who had received a
      second tier structured risk assessment in the course of their clinical care. A
      cohort analysis was carried out. Total scores for three risk assessment clusters
      (suicide, violence and self-neglect) were calculated and Cox regression models
      used to assess survival from first assessment. RESULTS: A total of 234 deaths had
      occurred over an average 9.4-month follow-up period. Mortality was relatively
      high for the cohort overall in relation to national norms [standardized mortality
      ratio 3.23, 95% confidence interval (CI) 2.83-3.67] but not in relation to other
      mental health service users with similar diagnoses. Only the score for the self
      neglect cluster predicted mortality [hazard ratio (HR) per unit increase 1.14,
      95% CI 1.04-1.24] with null findings for assessed risk of suicide or violence
      (HRs per unit increase 1.00 and 1.06 respectively). CONCLUSIONS: Level of
      clinician-appraised risk of self-neglect, but not of suicide or violence,
      predicted all-cause mortality among people receiving specific assessment of risk
      in a secondary mental health service.

PMID- 22153125
TI  - Primary surgery or neoadjuvant chemotherapy in ovarian cancer: what is the value
      of comparing apples with oranges?

PMID- 22153126
TI  - Advances in ovarian cancer disease control.

PMID- 22153127
TI  - The involvement of calcium carriers and of the vacuole in the glucose-induced
      calcium signaling and activation of the plasma membrane H(+)-ATPase in
      Saccharomyces cerevisiae cells.
AB  - Previous work from our laboratories demonstrated that the sugar-induced
      activation of plasma membrane H(+)-ATPase in Saccharomyces cerevisiae is
      dependent on calcium metabolism with the contribution of calcium influx from
      external medium. Our results demonstrate that a glucose-induced calcium (GIC)
      transporter, a new and still unidentified calcium carrier, sensitive to
      nifedipine and gadolinium and activated by glucose addition, seems to be
      partially involved in the glucose-induced activation of the plasma membrane H(+)
      ATPase. On the other hand, the importance of calcium carriers that can release
      calcium from internal stores was analyzed in glucose-induced calcium signaling
      and activation of plasma membrane H(+)-ATPase, in experimental conditions
      presenting very low external calcium concentrations. Therefore the aim was also
      to investigate how the vacuole, through the participation of both Ca(2+)-ATPase
      Pmc1 and the TRP homologue calcium channel Yvc1 (respectively, encoded by the
      genes PMC1 and YVC1) contributes to control the intracellular calcium
      availability and the plasma membrane H(+)-ATPase activation in response to
      glucose. In strains presenting a single deletion in YVC1 gene or a double
      deletion in YVC1 and PMC1 genes, both glucose-induced calcium signaling and
      activation of the H(+)-ATPase are nearly abolished. These results suggest that
      Yvc1 calcium channel is an important component of this signal transduction
      pathway activated in response to glucose addition. We also found that by a still
      undefined mechanism Yvc1 activation seems to correlate with the changes in the
      intracellular level of IP(3). Taken together, these data demonstrate that glucose
      addition to yeast cells exposed to low external calcium concentrations affects
      calcium uptake and the activity of the vacuolar calcium channel Yvc1,
      contributing to the occurrence of calcium signaling connected to plasma membrane
      H(+)-ATPase activation.

PMID- 22153128
TI  - Challenges for efficient health service delivery: experiences of dietitians
      completing their compulsory community service year in South Africa.
AB  - OBJECTIVE: To evaluate the successes and shortcomings of the community service
      programme implemented by the Department of Health (DOH) in South Africa by
      evaluating community service dietitians' experiences and challenges during the
      2009 community service year. DESIGN: The study employed both quantitative and
      qualitative research designs. A national survey was conducted using a
      questionnaire to illicit information on community service dietitians' working
      environments and the challenges they experienced. Furthermore individual
      interviews were conducted with a purposively selected subsample of community
      service dietitians to further explore issues that arose in the survey. SETTING:
      Data were collected from community service dietitians in the public health sector
      in South Africa. SUBJECTS: Dietitians completing their community service year in
      2009. RESULTS: Of the 168 community service dietitians placed in 2009, 134 (80 %)
      participated in the survey, while five community service dietitians in each
      province (n 45) were interviewed. Overall the community service dietitians were
      positive about the community service year and reported that it improved their
      confidence, skills and competencies. However, they experienced challenges related
      to the orientation programme, supervision/mentoring, resources available, patient
      referrals and communication. CONCLUSIONS: Despite the overall success of the
      community service year there are still challenges which the DOH needs to address
      in order to provide the best nutrition service possible for its patients.

PMID- 22153129
TI  - Oral health and bone mineral density in postmenopausal women.
AB  - OBJECTIVE: The objective of the study was to assess dental and periodontal status
      in relation to bone mineral density (BMD), and to study cytological changes in
      oral epithelium. METHODS: Thirty-seven postmenopausal women aged 50-70 were given
      a dental examination and a BMD assessment. RESULTS: There was a relationship
      between the femoral neck BMD and teeth state, a negative correlation between the
      lumbar BMD and the periodontal disease index (PDI) and between the radius BMD and
      the papillary bleeding index (PBI). PDI correlated positively with the number of
      superficial cells in the marginal gingiva smears. Correlation between PDI and
      parabasal cells and the number of teeth was negative. CONCLUSIONS: In observed
      postmenopausal women, there is a negative association between bone mineral
      density and teeth state and periodontal indices. Oral epithelium revealed
      atrophic changes resulting in low keratinization. The study suggests an
      association between decreasing in bone mineral density, alveolar bone loss and
      the numbers of various cell types in epithelial smears.

PMID- 22153131
TI  - Perioperative management of a parturient with hyponatraemia due to carbamazepine
      therapy.
AB  - We describe the perioperative management of an epileptic parturient who developed
      hyponatraemia due to carbamazepine therapy. Caesarean delivery was performed
      under combined spinal-epidural anaesthesia with a good outcome for both mother
      and neonate. The diagnostic and therapeutic approach, anaesthetic implications
      and maternal and neonatal risks for a patient with hyponatraemia complicating
      carbamazepine therapy are discussed.

PMID- 22153130
TI  - Effect of MU-opioid receptor A118G polymorphism on the ED50 of epidural
      sufentanil for labor analgesia.
AB  - BACKGROUND: A common polymorphism of the MU-opioid receptor gene (OPRM1,
      p.118A/G), which has been shown to effect the response to neuraxial opioids,
      occurs in 30% of Caucasian women. This double-blind up-down sequential allocation
      study was designed to examine the effect of p.118A/G on the ED50 of epidural
      sufentanil for labor analgesia. METHODS: Nulliparous women were recruited at 35
      weeks of gestation (n=77) and genotyped for p.118A/G. Those subsequently
      requesting epidural labor analgesia were enrolled. Each woman received epidural
      sufentanil diluted with 0.9% saline to a volume of 5 mL. The initial sufentanil
      dose was 21 MUg, with subsequent doses determined by the response of the previous
      patient (testing interval 1 MUg). Efficacy was accepted if the visual analogue
      score decreased to <10mm on a 100-mm scale within 30 min of drug administration.
      RESULTS: Twenty patients were excluded, leaving 57 women from whom data were
      analyzed: 33 in Group A (wild-type A118 homozygotes) and 24 in Group G
      (heterozygotes and homozygotes G118). The ED50 for epidural sufentanil was 25.2
      MUg in Group A (95% CI 23.2-26.4) and 20.2 MUg in Group G (95% CI 14.2-23.6)
      (P=0.03). The potency ratio for epidural sufentanil in Group G compared to Group
      A was 1.25 (95% CI 1.00-1.64). CONCLUSION: Women carrying the variant allele of
      p.118A/G of OPRM1 (G118) had a lower ED50 for epidural sufentanil given for early
      labor analgesia than women homozygous for the wild-type allele.

PMID- 22153132
TI  - Onset of labor epidural analgesia with ropivacaine and a varying dose of
      fentanyl: a randomized controlled trial.
AB  - BACKGROUND: This study was conducted to investigate the onset of labor epidural
      analgesia using 0.17% ropivacaine with a varying dose of fentanyl. We
      hypothesized that the onset of analgesia would be shortened in proportion to an
      increase in fentanyl dose. METHODS: Women requesting labor epidural analgesia
      were enrolled in this randomized controlled clinical trial. Each woman was
      randomly assigned to receive fentanyl 0, 50, 75, or 100 MUg with 0.17%
      ropivacaine 12 mL. The onset and duration of analgesia, the incidence of side
      effects and patient satisfaction were measured. RESULTS: Data from 102 women were
      analyzed. The onset of analgesia (mean +/- SD) was shortened with an increasing
      dose of fentanyl (14.3 +/- 5.4, 14.2 +/- 6.5, 12.1 +/- 5.1, and 8.7 +/- 3.8 min
      with fentanyl 0, 50, 75, or 100 MUg, respectively, P=0.001). The duration of
      analgesia was prolonged with an increasing dose of fentanyl (87.4 +/- 20.8, 112.3
      +/- 19.5, 140.8 +/- 18.8, and 143.6 +/- 18.6 min with fentanyl 0, 50, 75, or 100
      MUg, respectively, P<0.001). The incidence of pruritus increased with an
      increasing dose of fentanyl (P=0.027) but there were no differences for other
      maternal side effects. There was a significant difference in satisfaction score
      among groups (P=0.009). CONCLUSION: The addition of increasing doses of fentanyl
      to 0.17% ropivacaine contributed to shortened onset as well as prolonged duration
      of labor epidural analgesia and improved patient satisfaction.

PMID- 22153133
TI  - Transversus abdominis plane catheters for post-cesarean delivery analgesia: a
      series of five cases.
AB  - We present five cases of women who received ultrasound-guided transversus
      abdominis plane catheters for post-cesarean delivery analgesia. Pain relief was
      maintained with repeated boluses of local anesthetic combined with oral
      acetaminophen and ibuprofen unless contraindicated. We conclude that repeated
      dosing through transversus abdominis plane catheters may be offered to women as
      an alternative or adjuvant to intrathecal morphine. Larger studies to evaluate
      the safety and further refinements of this novel procedure are warranted.

PMID- 22153134
TI  - Impact of familiar and unfamiliar settings on cooking task assessments in frail
      older adults with poor and preserved executive functions.
AB  - BACKGROUND: Hospitalized frail older patients are usually assessed for their
      ability to perform some daily living activities in a clinical setting prior to
      discharge. However, assessments that take place in this unfamiliar environment
      might not be as representative of their functional performance as assessments at
      home. This may be related to a decline in some cognitive components, such as
      executive functions (EF), which enable one to cope with new environments. This
      study thus aims to compare cooking task performance in familiar and unfamiliar
      settings in a population of frail older adults with poor and preserved EF.
      METHODS: Thirty-seven frail older adults were assigned to one of two groups: poor
      EF or preserved EF. Participants performed two cooking tasks in familiar and
      unfamiliar settings, using a counterbalanced design. Their performance was
      assessed with a reliable tool based on observation of motor and process skills
      (Assessment of Motor and Process Skills). RESULTS: Thirty-three participants were
      retained for analysis. They demonstrated significantly better motor skills (F =
      5.536; p = 0.025) and process skills (F = 8.149; p = 0.008) in the familiar
      setting. The difference between settings was particularly marked for process
      skills in participants with poor EF (F = 16.920; p < 0.001). CONCLUSIONS: This
      study suggests that a home setting may be preferable for a more accurate
      assessment of cooking task performance in frail older adults, especially those
      with poor EF. These findings highlight the risk of underestimating frail older
      adults' performance when assessed in an unfamiliar setting (e.g. hospital), which
      could lead to inefficient allocation of home care services.

PMID- 22153135
TI  - Survey of directors of respiratory therapy departments regarding the future
      education and credentialing of respiratory care students and staff.
AB  - OBJECTIVE: Information and opinions were sought on the need for graduating and
      practicing respiratory therapists to obtain 66 competencies necessary for
      practice in 2015 and beyond, the required length of respiratory care programs,
      the educational needs of practicing therapists, current  and future workforce
      positions, and the appropriate credential needed by graduating therapists.
      METHODS: Survey responses from respiratory therapy department directors or
      managers are the basis of this report. After pilot testing and refining the
      questions, a self-administered, Internet based,  American Association for
      Respiratory Care (AARC) endorsed survey was used to gather information from 2,368
      individuals designated as respiratory therapy department directors or managers in
      the AARC membership list as of May 2010. RESULTS: A total of 663 valid survey
      responses (28.0%) were  received. On average, the vacancy rate of surveyed
      hospitals was only 0.81 full-time equivalents (FTEs). Responses by directors on
      66 competencies described in the second 2015 conference as needed by graduate and
      practicing respiratory therapists indicated 90% agreement on 37, between 50%  and
      90% agreement on 25, and < 50% agreement on 4 competencies. There was no
      consensus among directors on the academic preparation of new graduates, with 245
      (36.8%) indicating a preference for a baccalaureate or master's degree, 243
      (36.7%) indicating a preference for an associate degree,  and 176 (26.5%)
      indicating no preference. There were 270 (41.8%) respondents who indicated that a
      baccalaureate or master's degree in respiratory therapy should be required to
      qualify for a license to deliver respiratory care. The survey indicated that 523
      (81.2%) of directors are in favor  of the RRT credential being required to
      practice in 2015 and beyond. CONCLUSIONS: There was good agreement that graduate
      and practicing therapists should obtain the vast majority of the 66 competencies
      surveyed and that the entry level credential should be the RRT. Similar numbers
      of managers  favored an entry level baccalaureate degree as favored an associate
      degree.

PMID- 22153136
TI  - Celebrating 25 years.

PMID- 22153137
TI  - Hepatitis B vaccination for preterm infants.

PMID- 22153139
TI  - A survey of NAPNAP members' clinical and professional research priorities.
AB  - INTRODUCTION: The purpose of this methodological article is to describe the
      development, implementation, and analysis of the survey used to determine NAPNAP
      members' ranking of research priorities, to describe the top priorities ranked by
      participants, and to determine if priorities differed by area of practice
      (primary, acute, or specialty care) or participant age. METHOD: A cross-sectional
      descriptive design with an online survey was used. Completed by 324 NAPNAP
      members, the survey consisted of a demographic section and 90 statements in two
      domains: Clinical Priorities and Professional Role Priorities. RESULTS: Survey
      respondents strongly supported the top priorities with an average overall mean
      score of 4.0 or above on a 5-point Likert scale. Only three of the top 10
      clinical and professional priorities differed by area of practice. No clinical
      priorities and only three professional priorities differed by age. DISCUSSION:
      The survey results were used to develop the NAPNAP Research Agenda. Both the
      survey results and the agenda can provide guidance for the NAPNAP Board,
      committees and interests groups as they develop initiatives and programs.

PMID- 22153140
TI  - Care coordination in the spina bifida clinic setting: current practice and future
      directions.
AB  - INTRODUCTION: Although the potential benefits of care coordination are widely
      recognized, little is known about care coordination in the multidisciplinary
      spina bifida clinic setting. This study examined several aspects of care
      coordination in this environment. METHOD: We conducted semi-structured interviews
      with clinic staff (N = 43) and focus groups with caregivers (N = 38) at seven
      spina bifida clinics in the United States. RESULTS: Clinic staff described
      several primary goals of care coordination, including coordinating multiple
      services during one visit to ease the burden on families. Although the structure
      of care coordination varied across the clinics, several clinics had a dedicated
      care coordinator. Barriers and facilitators to care coordination included
      staffing issues, clinic day logistics, community resources, and family-related
      concerns. Despite challenges associated with care coordination processes, clinic
      staff and caregivers alike believed that care coordination is beneficial.
      DISCUSSION: Study findings suggest ways that care might be coordinated optimally
      in spina bifida clinics. A synthesis of these findings for clinics interested in
      implementing care coordination or improving the care coordination services they
      currently offer is provided.

PMID- 22153141
TI  - Factors that influence the likelihood of hiring a health care advocate for a
      chronically ill child.
AB  - INTRODUCTION: In response to the increasing complexity of the health care system,
      the field of health care advocacy has emerged. However, little is known about
      variables that may influence a person's likelihood of hiring a health care
      advocate (HCA) for their chronically ill child. METHODS: Severity (high or low)
      and probability of mortality (high or low) of a child's chronic illness and the
      child's age (1, 7, or 13 years) were manipulated using vignettes. The dependent
      variable was a composite score of the eight items used to measure the
      participants' likelihood of hiring an HCA. RESULTS: Participants (N = 1052) were
      more likely to hire an HCA for a child who was 1 year old than for a child who
      was 13 years old. Participants were more likely to hire an HCA for a child whose
      chronic illness was low rather than high in severity and whose chronic illness
      was high rather than low in probability of mortality. DISCUSSION: Use of an HCA
      may increase patient satisfaction, decrease medical errors, and enhance pediatric
      health outcomes.

PMID- 22153142
TI  - Shared medical appointments: facilitating care for children with asthma and their
      caregivers.
AB  - As important members of the health care team, patients and caregivers must be
      empowered to recognize their asthma status and to act accordingly. Education
      about asthma, complications, and successful management of asthma provide the best
      way to empower children and their caregivers. A Shared Medical Appointment (SMA)
      is a unique health care delivery approach that integrates disease management and
      patient education. The SMA described here is a 90-minute group appointment for
      four to nine patients who share a diagnosis of asthma, bronchospasm, or wheeze
      and their caregivers. The appointment includes a brief individual examination,
      health education delivered to the group, and the opportunity for interaction
      between group members. Because a supporting theoretic framework is not identified
      in the original design proposals for the SMA model or in the literature on its
      use, for the purposes of this project, Social Cognitive Theory is identified as
      the theoretical framework that best explains and reinforces the benefits of the
      SMA. The theoretic framework is important to direct the development and continued
      success of this treatment model. This project report describes the first nurse
      practitioner-led SMA as a tool for improving quality of care and service for
      children with asthma and their caregivers.

PMID- 22153143
TI  - Reducing stress in school-age girls through mindful yoga.
AB  - INTRODUCTION: School-age children report much stress in their daily lives, which
      may lead to psychological and physical problems. Mindfulness-based Stress
      Reduction is a program of awareness-based practices effective with adults. The
      purpose of this study was to investigate the efficacy of mindfulness training
      through yoga with school-age girls to reduce perceived stress, enhance coping
      abilities, self-esteem, and self-regulation, and explore the relationship between
      the dose of the intervention and outcomes. METHOD: Fourth- and fifth-grade girls
      were recruited from two public schools and randomly assigned to intervention and
      wait-list control groups. The intervention group met 1 hour a week for 8 weeks
      and completed 10 minutes of daily homework. RESULTS: Self-esteem and self
      regulation increased in both groups. The intervention group was more likely to
      report greater appraisal of stress (p < .01) and greater frequency of coping (p <
      .05). Homework accounted for 7% of the variance in reported stress. DISCUSSION:
      Consistent with reports of mindfulness training, greater awareness of the
      feelings associated with stress may enhance coping abilities. However, it is
      possible that the increasing awareness of stressors in itself increased stress,
      possibly as part of the process of developing mindfulness or related to
      cognitive, emotional, or social development. Mindfulness in children may differ
      from mindfulness in adults and warrants further investigation.

PMID- 22153144
TI  - Parents' dilemma: decisions concerning end-of-life care for their child.

PMID- 22153145
TI  - Acute and non-acute lower extremity pain in the pediatric population: part I.

PMID- 22153146
TI  - A description of nurse practitioner practice: results of a NAPNAP membership
      survey.

PMID- 22153147
TI  - Conducting school-based research: lessons learned from an after-school
      intervention study.
AB  - Although conducting research within schools poses challenges, the knowledge
      gained from studying children within the context of their lives and the
      availability of participants makes the school site a valuable site for research
      with children. The process of scheduling the research program, identifying an
      appropriate school site, recruiting and retaining participants, and knowing the
      optimal times and methods of contact is paramount to enhancing the success of a
      school based study.

PMID- 22153149
TI  - Adenosine improves post-procedural coronary flow but not clinical outcomes in
      patients with acute coronary syndrome: a meta-analysis of randomized trials.
AB  - AIMS: Adjunctive therapy with adenosine has been shown to improve coronary flow
      in patients with acute coronary syndromes (ACS); it is unclear, however, whether
      adenosine can effectively reduce adverse clinical events. The aim of our study
      was to perform a meta-analysis of all randomized controlled trials (RCTs)
      investigating angiographic and clinical outcomes in ACS patients undergoing PCI
      or thrombolysis and receiving adjunctive adenosine therapy vs. placebo. METHODS:
      Medline/CENTRAL/EMBASE and Google Scholar database were scanned. The meta
      analysis included ten RCTs (N=3821). All-cause mortality was chosen as primary
      endpoint. Secondary endpoints were re-infarction (MI), heart failure (HF)
      symptoms (NYHA class III/IV), no-reflow (defined as TIMI 0 flow) and >50% ST
      resolution. RESULTS: Adenosine compared to placebo was associated with a
      significant reduction of post-procedural no-reflow (OR [95% CI]=0.25 [0.08-0.73],
      p=0.01); however, at a median follow-up of 6 months, prior treatment with
      adenosine did not confer significant benefits in terms of reduction of mortality
      (OR(Fixed) [95% CI]=0.87 [0.69-1.09], p=0.23), as well as re-MI (p=0.80), HF
      symptoms (p=0.44) and ST-resolution (p=0.09). Separate analyses conducted in the
      subgroups of ST-elevation MI patients treated with either PCI or thrombolysis
      confirmed the findings found in the overall population. CONCLUSIONS: This meta
      analysis shows that adenosine adjunctive therapy does not improve survival nor
      reduce the rates of re-MI and HF symptoms in patients with ACS treated with PCI
      or thrombolysis. The beneficial effect on post-procedural coronary flow was not
      associated with consistent advantages on clinical outcomes.

PMID- 22153150
TI  - Hydrogen-rich saline prevents neointima formation after carotid balloon injury by
      suppressing ROS and the TNF-alpha/NF-kappaB pathway.
AB  - BACKGROUND: Reactive oxygen species (ROS) play a pivotal role in neointima
      hyperplasia after balloon injury. Molecular hydrogen has emerged as a novel
      antioxidant and has been proven effective in treating many diseases. OBJECTIVES:
      We aimed to determine the mechanism by which hydrogen affects neointima
      formation. METHODS: We assessed the influence of a hydrogen-rich saline solution
      (HRSS) by daily injection in rats. Rats were euthanized to evaluate the
      neointima. ROS, malondialdehyde (MDA) and superoxide dismutase (SOD) and reduced
      glutathione (GSH), were detected in the injured artery. Macrophage infiltration
      and the production of inflammatory factors (i.e., IL-6, TNF-alpha and NF-kappaB)
      were also observed. The in vitro effects of hydrogen on vascular smooth muscle
      cell (VSMC) proliferation were also measured. RESULTS: HRSS decreased the
      neointima area significantly. The neointima/media ratio was also reduced by HRSS.
      There was a decline in the number of PCNA-positive cells in the intima treated
      with HRSS. Meanwhile, HRSS ameliorated the ROS and MDA levels and increased SOD,
      reduced GSH levels in the injured carotid. In addition, the levels of
      inflammatory factors, such as IL-6, TNF-alpha and NF-kappaB p65, were attenuated
      by HRSS. In vitro studies also confirmed the anti-proliferative capability of the
      hydrogen solution and ROS generation in VSMCs induced by PDGF-BB. CONCLUSION:
      HRSS may have a protective role in the prevention of neointima hyperplasia and
      restenosis after angioplasty. HRSS may partially exert its role by neutralizing
      the local ROS and suppressing the TNF-alpha/NF-kappaB pathway.

PMID- 22153151
TI  - Temporal profile and prognostic value of Lp-PLA2 mass and activity in the acute
      stroke setting.
AB  - BACKGROUND: Lp-PLA2 is a novel biomarker in cardiovascular diseases due to its
      ability to predict first-ever and recurrent stroke. Little information is known
      regarding its influence on early outcome after stroke. OBJECTIVES: We aimed to
      investigate Lp-PLA2 in t-PA-treated stroke patients and to study its relationship
      with early outcome. METHODS: Lp-PLA2 mass and activity were measured in 135
      healthy controls and also in stroke patients treated with t-PA at baseline (n=99)
      and serially thereafter (n=34) by means of the PLAC test at an automated Olympus
      analyzer and by a colorimetric activity method (diaDexus). NIHSS scores and TCD
      recordings were also obtained serially. Outcome was defined according to early
      neurological status, the presence of arterial recanalization and functional
      outcome at third month. RESULTS: Lp-PLA2 mass was increased as compared to
      controls, whereas Lp-PLA2 activity was significantly decreased at baseline as
      compared with controls and with 1 and 24 h determinations. Lp-PLA2 mass and
      activity were not related with early (48 h) neurological status. Regarding
      recanalization, higher mass and activity were found among patients who did not
      achieve complete recanalization by the end of t-PA treatment (p=0.029 for mass,
      p=0.044 for activity). Lp-PLA2 mass and the existence of a proximal occlusion at
      baseline were the most powerful predictors for persistent occlusions (OR for
      proximal occlusion 6.8. p=0.036, OR for Lp-PLA2 mass 7.2 per standard deviation
      increase, p=0.008). CONCLUSIONS: Significant changes in Lp-PLA2 concentrations
      occur early after stroke onset. Lp-PLA2 mass may add relevant information
      regarding early arterial recanalization in intravenous t-PA-treated stroke
      patients.

PMID- 22153152
TI  - Relationship of serum fatty acid composition and desaturase activity to C
      reactive protein in Japanese men and women.
AB  - BACKGROUND: Although fatty acid composition in serum and desaturase activity,
      which alters serum fatty acid composition, has been associated with C-reactive
      protein (CRP) concentration in Western populations, no study has been carried out
      in non-Western populations. We examined the association of serum fatty acids and
      estimated desaturase activity with CRP concentrations in Japanese men and women.
      METHODS: Subjects were 489 Japanese municipal employees aged 21-67 years who
      participated in a survey at the time of a periodic health check-up. Serum high
      sensitivity CRP concentrations were measured using the latex agglutination
      nephelometry method. Fatty acid composition was measured in serum cholesteryl
      esters and desaturase activities by fatty acid product-to-precursor ratios.
      Relationships were assessed using multiple regression. RESULTS: Serum CRP
      concentration was positively associated with palmitic acid (P for trend=0.002)
      and inversely with alpha-linolenic acid (P for trend=0.01) in men, and positively
      with dihomo-gamma-linolenic acid (P for trend in men or women=0.01) and inversely
      with delta-5-desaturase (20:4n-6/20:3n-6) (P for trend in men and women=0.05 and
      0.002, respectively) in men and women. CONCLUSIONS: Low-grade inflammation may be
      associated with a serum fatty acid pattern of high palmitic acid or low alpha
      linolenic acid in men, and of high dihomo-gamma-linolenic acid or low delta-5
      desaturase in both sexes.

PMID- 22153153
TI  - Malignant small round blue cell tumor of the kidney without EWSR1 rearrangement:
      report of a case and review of the literature.

PMID- 22153154
TI  - [Perception and psychological impact of an abnormal Pap smear. Results of a
      comparative European survey].
AB  - OBJECTIVES: The availability of information on HPV and Pap tests has increased
      dramatically with the introduction of national HPV vaccination programs. But data
      on the effectiveness of this information is limited. However, our desire is to
      reduce patient anxiety and promote better delivery of information. PATIENTS AND
      METHODS: Therefore a questionnaire-based cohort study was conducted to
      investigate women's experience with the announcement of an abnormal Pap smear
      result, then the ensuing events, as well as their practitioner's management. This
      article focuses on the French experience, underpinned by comparative data with
      Spain and Portugal. RESULTS: It shows that, face with stress reactions and
      patient's anxiety, the level of information from the medical profession is still
      seen as inadequate, while the Internet as an information source has its
      limitations and dangers. The close entourage is most relied on, which supports
      the need for better public information. DISCUSSION AND CONCLUSION: Uniformity and
      standardization of information strategies is not yet on European time.

PMID- 22153155
TI  - Mechanical control of spheroid growth: distinct morphogenetic regimes.
AB  - We develop a model of transport and growth in epithelio-mesenchymal interactions.
      Analysis of the growth of an avascular solid spheroid inside a passive mesenchyme
      or gel shows that sustained volumetric growth requires four generic mechanisms:
      (1) growth factor, (2) protease, (3) control of cellularity, and (4) swelling.
      The model reveals a bifurcation delineating two distinct morphogenetic regimes:
      (A) steady growth, (B) growth arrested by capsule formation in the mesenchyme. In
      both morphogenetic regimes, growth velocity is constant unless and until a
      complete capsule forms. Comprehensive exploration of the large parameter space
      reveals that the bifurcation is determined by just two ratios representing the
      relative strengths of growth and proteolytic activity. Growth velocity is
      determined only by the ratio governing growth, independent of proteolytic
      activity. There is a continuum of interior versus surface growth, with fastest
      growth at the surface. The model provides a theoretical basis for explaining
      observations of growth arrest despite proteolysis of surrounding tissue, and
      gives a quantitative framework for the design and interpretation of experiments
      involving spheroids, and tissues which are locally equivalent to spheroids.

PMID- 22153157
TI  - Ectosomes.

PMID- 22153156
TI  - Dissociation of neuronal and psychophysical responses to local and global motion.
AB  - Most neurons in cortical area MT (V5) are strongly direction selective, and their
      activity is closely associated with the perception of visual motion. These
      neurons have large receptive fields built by combining inputs with smaller
      receptive fields that respond to local motion. Humans integrate motion over large
      areas and can perceive what has been referred to as global motion. The large size
      and direction selectivity of MT receptive fields suggests that MT neurons may
      represent global motion. We have explored this possibility by measuring responses
      to a stimulus in which the directions of simultaneously presented local and
      global motion are independently controlled. Surprisingly, MT responses depended
      only on the local motion and were unaffected by the global motion. Yet, under
      similar conditions, human observers perceive global motion and are impaired in
      discriminating local motion. Although local motion perception might depend on MT
      signals, global motion perception depends on mechanisms qualitatively different
      from those in MT. Motion perception therefore does not depend on a single
      cortical area but reflects the action and interaction of multiple brain systems.

PMID- 22153158
TI  - The optimism bias.

PMID- 22153159
TI  - The rubber hand illusion increases histamine reactivity in the real arm.

PMID- 22153160
TI  - Heightened neural reactivity to threat in child victims of family violence.

PMID- 22153161
TI  - Mitochondrial-ER tethering: the inheritance of a functional unit.
AB  - A new study uncovers a novel role for the endoplasmic reticulum in tethering
      mitochondria specifically at the tip of the growing bud in Saccharomyces
      cerevisiae. Mitochondrial anchoring to the bud tip requires the tethering factor
      Mmr1, and the link to the ER is coupled to the cell cycle through a
      phosphorylation-dependent mechanism.

PMID- 22153162
TI  - Comparative cognition: united we stand.
AB  - Humans engage in collaborative activities far more often than do members of any
      other species. Two recent studies explore why this is the case. Are humans
      uniquely motivated to work together?

PMID- 22153163
TI  - Adaptive radiations: there's something about finches.
AB  - A phylogenetic tree for the extant Hawaiian honeycreepers charts their
      diversification over the past 6 million years.

PMID- 22153164
TI  - Cortical circuits: finding balance in the brain.
AB  - Maintaining the right balance between excitation and inhibition is crucial to
      healthy brain function. A recent study has used optogenetics to show how quickly
      and effectively inhibition clamps down a novel burst of excitation in the
      neocortex.

PMID- 22153165
TI  - Cell differentiation: midbody remnants - junk or fate factors?
AB  - The midbody is an electron-dense structure that forms between two dividing
      daughter cells, and a midbody remnant is left after completion of cell
      separation. This structure has been regarded as a piece of cellular debris, but
      two recent papers suggest an unexpected function for the midbody remnant in
      promoting an undifferentiated cellular phenotype.

PMID- 22153166
TI  - Invertebrate neuroethology: food play and sex.
AB  - How do animals perceive their environment and make appropriate behavioral choices
      based on those perceptions? New data have uncovered a novel sensory pathway that
      promotes Drosophila male courtship behavior in response to food.

PMID- 22153167
TI  - Spatial representation: maps in a temporal void.
AB  - It has been suggested that the matrix-like firing structure of entorhinal grid
      cells is caused by interference between membrane oscillations at slightly
      different theta frequencies. A recent report suggests that grid signals can be
      generated in the absence of theta oscillations.

PMID- 22153168
TI  - Invertebrate evolution: bringing order to the molluscan chaos.
AB  - While the seven classes within the phylum Mollusca are clearly defined
      morphologically and molecularly, relationships between them have long been
      contentious. Two recent phylogenomic studies take an important step forward with
      intriguing implications for their evolution.

PMID- 22153169
TI  - Auditory perception: hearing the texture of sounds.
AB  - A recent study provides intriguing insights into how we recognize the sound of
      everyday objects from the statistical properties of the textures they produce.

PMID- 22153170
TI  - Prediabetes, CANRISK and screening in Canada.

PMID- 22153171
TI  - Nova Scotia Prediabetes Project: upstream screening and community intervention
      for prediabetes and undiagnosed type 2 diabetes.
AB  - INTRODUCTION: Identifying individuals in the prediabetic state may help
      delay/prevent disease progression to type 2 diabetes mellitus. We explored the
      feasibility of a household mailing approach for population-based screening of
      prediabetes and unidentified type 2 diabetes mellitus, developed standard
      protocol, and developed and implemented community-based lifestyle programs.
      METHODS: The 16-item Canadian Diabetes Risk Assessment Questionnaire (CANRISK)
      was mailed to every household in two rural Nova Scotia communities. In total 417
      participants aged 40 to 74 years with no prior diagnosis of diabetes self
      administered the CANRISK and completed a 2-hour oral glucose tolerance test
      (OGTT) at a local health care facility. Those with prediabetes were invited to
      participate in a Prediabetes Lifestyle Program. RESULTS: Glycemic status was
      identified as normal, prediabetes or diabetes for 84%, 13% and 3% of
      participants, respectively. Association between glycemic status and overall
      CANRISK risk score was statistically significant. Six CANRISK items were
      significantly associated with glycemic status: body mass index, waist
      circumference, history of hypertension and hyperglycemia, education and perceived
      health status. Participants and physicians gave positive feedback on the CANRISK
      screening process. CONCLUSION: The CANRISK holds promise as a population-based
      screening tool.

PMID- 22153172
TI  - Piloting the CANRISK tool in Vancouver Coastal Health.
AB  - INTRODUCTION: Vancouver Coastal Health Authority's Healthy Living Program
      implemented this pilot study to test and validate the Canadian Diabetes Risk
      Assessment Questionnaire (CANRISK) developed by the Public Health Agency of
      Canada as a screening tool for undiagnosed type 2 diabetes mellitus (DM) and
      prediabetes. Key objectives were to test the feasibility and acceptability of
      screening urban ethnic groups using the CANRISK, increase awareness of risk
      factors for DM and preDM and develop resources for lifestyle change. METHODS: The
      study recruited participants through community groups and churches,
      intraorganizational emails, primary care clinics and word of mouth. They
      completed the CANRISK and an oral glucose tolerance test (OGTT) either
      individually or as part of a group. Groups received a brief diabetes prevention
      information session. Documents to support lifestyle change were distributed to
      all participants. RESULTS: Participants (n = 556) were recruited among East
      Asian, Caucasian, South Asian and Latin American ethnic groups. Of these, 17% had
      OGTT results in the preDM range and 3% in the DM range. Over 90% of participants
      reported that the CANRISK wording was clear and that they had received useful
      information about lowering their diabetes risk. CONCLUSION: The benefit of using
      an OGTT was in identifying 11% of the sample of participants who had impaired
      glucose tolerance (IGT) and did not show abnormal fasting plasma glucose (FPG)
      results. All participants with abnormal laboratory results were provided with
      follow-up educational interventions in their own language.

PMID- 22153173
TI  - Validating the CANRISK prognostic model for assessing diabetes risk in Canada's
      multi-ethnic population.
AB  - INTRODUCTION: Despite high rates of undiagnosed diabetes and prediabetes,
      suitable risk assessment tools for estimating personal diabetes risk in Canada
      are currently lacking. METHODS: We conducted a cross-sectional screening study
      that evaluated the accuracy and discrimination of the new Canadian Diabetes Risk
      Assessment Questionnaire (CANRISK) for detecting diabetes and prediabetes
      (dysglycemia) in 6223 adults of various ethnicities. All participants had their
      glycemic status confirmed with the oral glucose tolerance test (OGTT). We
      developed electronic and paper-based CANRISK scores using logistic regression,
      and then validated them against reference standard blood tests using test-set
      methods. We used area under the curve (AUC) summary statistics from receiver
      operating characteristic (ROC) analyses to compare CANRISK with other alternative
      risk-scoring models in terms of their ability to discern true dysglycemia.
      RESULTS: The AUC for electronic and paper-based CANRISK scores were 0.75 (95% CI:
      0.73-0.78) and 0.75 (95% CI: 0.73-0.78) respectively, as compared with 0.66 (95%
      CI: 0.63-0.69) for the Finnish FINDRISC score and 0.69 (95% CI: 0.66-0.72) for a
      simple Obesity model that included age, BMI, waist circumference and sex.
      CONCLUSION: CANRISK is a statistically valid tool that may be suitable for
      assessing diabetes risk in Canada's multi-ethnic population. CANRISK was
      significantly more accurate than both the FINDRISC score and the simple Obesity
      model.

PMID- 22153174
TI  - 2008 Niday Perinatal Database quality audit: report of a quality assurance
      project.
AB  - INTRODUCTION: This quality assurance project was designed to determine the
      reliability, completeness and comprehensiveness of the data entered into Niday
      Perinatal Database. METHODS: Quality of the data was measured by comparing data
      re-abstracted from the patient record to the original data entered into the Niday
      Perinatal Database. A representative sample of hospitals in Ontario was selected
      and a random sample of 100 linked mother and newborn charts were audited for each
      site. A subset of 33 variables (representing 96 data fields) from the Niday
      dataset was chosen for re-abstraction. RESULTS: Of the data fields for which
      Cohen's kappa statistic or intraclass correlation coefficient (ICC) was
      calculated, 44% showed substantial or almost perfect agreement (beyond chance).
      However, about 17% showed less than 95% agreement and a kappa or ICC value of
      less than 60% indicating only slight, fair or moderate agreement (beyond chance).
      DISCUSSION: Recommendations to improve the quality of these data fields are
      presented.

PMID- 22153175
TI  - Identifying potentially eligible subjects for research: paper-based logs versus
      the hospital administrative database.
AB  - INTRODUCTION: The Canadian Perinatal Network (CPN) is a national database focused
      on threatened very pre-term birth. Women with one or more conditions most
      commonly associated with very pre-term birth are included if admitted to a
      participating tertiary perinatal unit at 22 weeks and 0 days to 28 weeks and 6
      days. METHODS: At BC Women's Hospital and Health Centre, we compared traditional
      paper-based ward logs and a search of the Canadian Institute for Health
      Information (CIHI) electronic database of inpatient discharges to identify
      patients. RESULTS: The study identified 244 women potentially eligible for
      inclusion in the CPN admitted between April and December 2007. Of the 155
      eligible women entered into the CPN database, each method identified a similar
      number of unique records (142 and 147) not ascertained by the other: 10 (6.4%) by
      CIHI search and 5 (3.2%) by ward log review. However, CIHI search achieved these
      results after reviewing fewer records (206 vs. 223) in less time (0.67 vs. 13.6
      hours for ward logs). CONCLUSION: Either method is appropriate for identification
      of potential research subjects using gestational age criteria. Although
      electronic methods are less time-consuming, they cannot be performed until after
      the patient is discharged and records and charts are reviewed. Each method's
      advantages and disadvantages will dictate use for a specific project.

PMID- 22153176
TI  - Research methods of the Youth Smoking Survey (YSS).
AB  - This paper describes the survey development, design and data collection protocol
      for the 2008/2009 Youth Smoking Survey (YSS) and the changes to the YSS survey
      and protocols across the 5 survey cycles (1994, 2002, 2004/2005, 2006/2007,
      2008/2009). Canada's Youth Smoking Survey is a nationally representative school
      based survey of students (grades 6 to 12 in 2008/2009) from randomly sampled
      public and private schools in the ten provinces. The main objective of the YSS is
      to provide benchmark data on national smoking prevalence rates for youth. Key
      features of the 2008/2009 YSS include consistent measures across survey cycles, a
      survey team of researchers and non-governmental organizations, a link to school
      and student level measures, provision of tailored feedback reports to schools and
      publicly available datasets.

PMID- 22153178
TI  - Management of mandibular fractures in children with a split acrylic splint: a
      case series.
AB  - Five children with mandibular fractures were treated with a split acrylic splint,
      which secured the fracture by wiring around the mandible. The occlusion was
      satisfactory, without infection or malocclusion. None required revision, and
      there was no deviation of the mandible, ankylosis, or disturbances of growth.

PMID- 22153179
TI  - Lingual necrosis secondary to mucormycosis.
AB  - Mucormycosis is a rare fungal infection with a high mortality that affects
      immunocompromised patients. This is an unusual case of necrosis of the tongue in
      a patient with pulmonary mucormycosis, diabetes mellitus, and aplastic anaemia.

PMID- 22153180
TI  - Three-dimensional fixation of fractures of the mandibular condyle with a
      resorbable three-dimensional osteosynthesis mesh.
AB  - We describe the use of a resorbable mesh fixed by ultrasound-activated pins, and
      report the satisfactory outcome in the first 5 patients treated.

PMID- 22153181
TI  - Cleft palate and bilateral congenital cataract: a familial observation: a new
      syndrome?
AB  - We report a family with a rare association of congenital bilateral cataract and
      cleft palate that has not to our knowledge been previously reported. The lineage
      has unveiled abnormalities over four generations affecting 21 people with
      congenital bilateral cataract, with or without cleft palate. The transmission
      seems autosomal dominant. Four brothers and sisters presented with this defect,
      and a fifth sister is healthy. The mother has facial dimorphism, congenital
      bilateral cataract, submucous cleft palate, clinodactyly, and scoliosis. The
      propositus' karyotype was normal. Array comparative genomic hybridisation (CGH)
      analysis showed an interstitial amplification in Xp21.1, found in the mother, in
      all the affected siblings but one, and in the healthy girl. Thisl association is
      not rare and has been reported in over 50 syndromes but rarely in familial
      observations. Based on the genetic-clinical discordance we wonder about the
      deleterious impact of the Xp21.1 amplification that might be a copy number
      polymorphism.

PMID- 22153182
TI  - Incidence and impact of previous orthodontic treatment in patients attending
      orthognathic combined clinics: a survey.
AB  - This prospective questionnaire-based study was designed to determine the
      incidence of patients attending orthognathic combined clinics who have previously
      had orthodontic treatment, and to assess the impact, if any, this has had on
      their proposed surgical treatment. Contemporaneous and historical data from
      consecutive patients at different stages of treatment who were attending clinics
      at two London hospitals during a three-month period were included. In total 22/56
      patients (39%) had previously had orthodontic treatment, and of those, it had had
      an undesirable effect on the current management of 10 (45%). The effects included
      a reduced range of dental movements available to orthodontists (8/23, 35%),
      undesirable extractions (5/23, 22%), and a prolonging of preoperative
      orthodontics (5/23, 22%). The median age at which previous orthodontic treatment
      had been started was 13.5 (range 11-26). Nearly a third of patients reported that
      they had not been advised by their referring practitioner that a combined
      orthodontic and surgical approach might be required. The study suggests that
      preliminary assessment should be improved. Patients should be informed about and
      prevented from undergoing orthodontic treatment that may limit future surgical
      management, otherwise they may have to face repeated and prolonged orthodontic
      treatment, unexpected operations, and potential limitations to the outcome of
      surgical treatment. This could be achieved through the training and education of
      all practitioners and the development of referral guidelines.

PMID- 22153183
TI  - Is a liver biopsy necessary? Investigation of a suspected hepatocellular
      carcinoma: a pictorial essay of hepatocellular carcinoma and the revised American
      Association for the Study of Liver Disease criteria.

PMID- 22153184
TI  - A systematic review-meta-analysis of primary research investigating the effect of
      selected alternative treatments on gastrointestinal nematodes in sheep under
      field conditions.
AB  - Selected alternative treatments for preventing or controlling gastrointestinal
      nematodes (GIN) in sheep under field conditions were evaluated using a systematic
      review-meta-analysis methodology. Forty-three publications reporting 51 studies
      (21 controlled studies (CS) and 30 challenge studies (ChS)) and 85 unique
      treatment comparisons were included in the review. The alternative treatment
      categories were nutraceuticals (28 studies), breeding for genetic resistance
      (12), nutritional manipulation (6), homeopathies (2), administration of copper
      oxide wire particles (2), and biological control (1). Random effect meta-analyses
      (MA) and meta-regression were performed with the natural logarithm of the
      difference in means (lnMD) between the control and treatment groups, for fecal
      egg counts per gram of wet feces (FEC), worm counts (WC) or fecal egg counts per
      gram of dry matter (FECDM) as the outcome. Treatment effect estimates (lnMD) were
      back-transformed to their count ratios (CR), a relative measure of effect for
      controlled versus treated groups, for presentation of results. Significant
      heterogeneity was observed for both CS and ChS that evaluated nutraceuticals,
      genetic resistance and nutrition treatments. MA of ChS that investigated
      nutraceuticals resulted in a significant overall CR of 1.62 (P<0.01) and 1.64
      (P<0.01) for FEC and FECDM, respectively and a marginal significant CR of 1.14
      (P=0.06) for WC, all favoring the treated groups. MA of CS and ChS that
      investigated genetic resistance resulted in a significant overall CR of 5.89 and
      15.42, respectively (P<0.01), again favoring treated groups. MA of CS that
      investigated homeopathies with FEC as an outcome were homogenous (I(2)=0.0%) and
      resulted in a non-significant pooled CR of 1.61. ChS investigating copper oxide
      wire particle treatments and WC as an outcome, were homogenous (I(2)=0.0%) and
      had a marginally significant pooled CR of 1.68 (P=0.06). Publication bias was
      observed for ChS with WC outcomes, indicating that small size studies reporting
      non-significant CR, were less likely to be published than similar studies that
      found a significant CR. In a meta-regression, randomization (6.2%) and study size
      (29.2%) were the main factors contributing to the total variation when the
      outcome was FEC, and none of the variables contributed to between study
      heterogeneity. When the outcome was WC, type of treatment was the only
      significant covariate, explaining 6% of the heterogeneity and 38.5% of the total
      variation. The methodological soundness and reporting of primary research in the
      selected studies were low. Our results indicate that from the studied alternative
      treatments, nutraceuticals and use of genetically resistant sheep might be more
      promising for control of GINs in sheep.

PMID- 22153186
TI  - Radio-frequency heating to inactivate Salmonella Typhimurium and Escherichia coli
      O157:H7 on black and red pepper spice.
AB  - The efficacy of radio-frequency (RF) heating to inactivate Salmonella Typhimurium
      and Escherichia coli O157:H7 on black and red pepper spice was investigated. A
      27.12 MHz RF heating system consisted of two parallel-plate electrodes was used,
      with the sample being placed between them. Black peppers (whole and ground) and
      red peppers (+ 16 mesh, -16 + 25 mesh, and -25 mesh) inoculated with S.
      Typhimurium and E. coli O157:H7 were treated with RF energy during 50s for black
      peppers and 40s for red peppers, and color change of samples was evaluated after
      treatment. RF heating for 50s resulted in 2.80 to 4.29 log CFU/g reductions of S.
      Typhimurium and E. coli O157:H7 in black peppers and RF heating of red peppers
      for 40s reduced pathogens by 3.38 log CFU/g to more than 5 log CFU/g (below the
      detection limit) without affecting the color quality change. The results suggest
      that RF heating has the potential for novel thermal process to control foodborne
      pathogens in spice.

PMID- 22153185
TI  - Absence of mutations in the activation loop and juxtamembrane domains of VEGFR-1
      and VEGFR-2 gene in chronic myelomonocytic leukemia (CMML).

PMID- 22153187
TI  - Self-deception's adaptive value: effects of positive thinking and the winner
      effect.
AB  - There is a puzzle about why self-deception, a process that obscures the truth, is
      so pervasive in human behavior given that tracking the truth seems important for
      our survival and reproduction. William von Hippel and Robert Trivers argue that,
      despite appearances, there is good reason to think that self-deception is an
      adaptation by arguing: (1) self-deception leads to a positive self-perception and
      (2) a positive self-perception increases an individual's fitness. D.S. Neil Van
      Leeuwen, however, gives persuasive arguments against both steps. In response, we
      will defend both propositions, thereby supporting the conclusion that self
      deception indeed has adaptive value. The first premise will be bolstered by a
      survey of the philosophical literature and empirical work on self-deception,
      whereas the second will be strengthened by empirical research on a behavioral
      phenomenon known as the winner effect.

PMID- 22153188
TI  - Health in Afghanistan: hope and future.

PMID- 22153189
TI  - Lessons from Lipitor and the broken blockbuster drug model.

PMID- 22153190
TI  - What constitutes full access to data in industry-funded trials?

PMID- 22153191
TI  - Postgraduate medical education in England: 100 years of solitude.

PMID- 22153193
TI  - Anand Grover: leading the defence of human rights.

PMID- 22153194
TI  - Dietary salt and cardiovascular disease.

PMID- 22153195
TI  - Dietary salt and cardiovascular disease.

PMID- 22153196
TI  - Dietary salt and cardiovascular disease.

PMID- 22153197
TI  - Sharing of research data.

PMID- 22153199
TI  - Sharing of research data.

PMID- 22153200
TI  - Access to data in industry-sponsored trials.

PMID- 22153201
TI  - Routine blood tests? Helping you live(r) longer!

PMID- 22153202
TI  - Post-stroke dementia: the contribution of thalamus and basal ganglia changes.
AB  - BACKGROUND: The neurobiological basis of increased risk of dementia in stroke
      patients is unclear, though there are several related pathological changes,
      including white matter hyperintensities (WMH), and medial temporal atrophy.
      Subcortical gray matter structures have also been implicated in dementia
      resulting from vascular pathology, particularly vascular dementia. This study
      aimed to investigate the contribution of changes in subcortical gray matter
      structures to post-stroke dementia (PSD). METHODS: T1- and T2-weighted images and
      T2-weighted fluid-attenuated inversion recovery (FLAIR) images were obtained on a
      3-Tesla magnetic resonance (MR) system, in four groups aged over 75 years: post
      stroke with dementia (PSD; 8), post-stroke no dementia (PSnoD; 33), Alzheimer's
      disease (AD; 26) and controls (30). Automated software was used to measure the
      volume of thalamus, putamen, caudate nucleus, and hippocampus as well as total
      WMH volume. The number of subcortical lacunes was also counted. RESULTS: The
      number of caudate lacunes was higher in the PSnoD group, compared with AD (p =
      0.029) and controls (p = 0.019). The putamen volume was smaller in the stroke and
      AD groups, when compared with controls. In the whole stroke group, putamen
      lacunes were correlated with impairment in memory (Rey test; rho = -0.365; p =
      0.031), while WMH and hippocampal volume both correlated with global dysfunction.
      CONCLUSION: Our findings implicate a variety of neurobiological substrates of
      dementia, such as small vessel disease and Alzheimer pathology, which develop
      after stroke in an old older population, with a contribution from subcortical
      brain structures.

PMID- 22153204
TI  - The effects of working height and manipulated weights on subjective strain, body
      posture and muscular activity of milking parlor operatives--laboratory study.
AB  - The incidence of work-related musculoskeletal disorders among milking parlor
      operatives has increased while milking parlors were getting bigger. At the same
      time parlor design was improved regarding the physical load as well as body
      postures. In contrast to former studies on workload in parlor milking this
      project was designed and performed as an experimental study in a laboratory
      setting including 6 female subjects. Motion analysis and psycho-physiological
      analysis (EMG, heart rate, subjective perceived strain index) were carried out.
      Intra-individual comparisons were made for the different settings using general
      linear models for repeated measurements. The effects of working height and weight
      of milking unit during parlor milking were investigated regarding the impact on
      muscular load and body posture. The results showed that the optimal working
      height for attaching the cluster is having the teats at shoulder level of the
      parlor operative. Another important workload reduction was achieved by reducing
      the weight of the milking cluster. The named discomfort, localized fatigue and
      the body posture analysis provide evidence that the changes in modern milking
      parlors due to mechanization still bear the risk of overburden for the worker.

PMID- 22153205
TI  - Kinetic optimisation of the reversed phase liquid chromatographic separation of
      rooibos tea (Aspalathus linearis) phenolics on conventional high performance
      liquid chromatographic instrumentation.
AB  - Rooibos tea, produced from the endemic South African shrub Aspalathus linearis,
      has various health-promoting benefits which are attributed to its phenolic
      composition. Generating reliable, quantitative data on these phenolic
      constituents is the first step towards documenting the protective effects
      associated with rooibos tea consumption. Reversed phase liquid chromatographic
      (RP-LC) methods currently employed in the quantitative analysis of rooibos are,
      however, hampered by limited resolution and/or excessive analysis times. In order
      to overcome these limitations, a systematic approach towards optimising the RP-LC
      separation of the 15 principal rooibos tea phenolics on a 1.8 MUm phase using
      conventional HPLC instrumentation was adopted. Kinetic plots were used to obtain
      the optimal configuration for the separation of the target analytes within
      reasonable analysis times. Simultaneous optimisation of temperature and gradient
      conditions provided complete separation of these rooibos phenolics on a 1.8 MUm
      C18 phase within 37 min. The optimised HPLC-DAD method was validated and
      successfully applied in the quantitative analysis of aqueous infusions of
      unfermented and fermented rooibos. Major phenolic constituents of fermented
      rooibos were found to be a phenylpropanoid phenylpyruvic acid glucoside (PPAG),
      the dihydrochalcone C-glycoside aspalathin, the flavones isoorientin and
      orientin, and a flavonol O-diglycoside tentatively identified as quercetin-3-O
      robinobioside. Content values for PPAG, ferulic acid and quercetin-3-O
      robinobioside in rooibos are reported here for the first time. Mass spectrometric
      (MS) and tandem MS detection were used to tentatively identify 13 additional
      phenolic compounds in rooibos infusions, including a new luteolin-6-C-pentoside-8
      C-hexoside and a novel C-8-hexosyl derivative of aspalathin reported here for the
      first time.

PMID- 22153206
TI  - Argentation chromatography for the separation of polycyclic aromatic compounds
      according to ring number.
AB  - Crude oils are the most complex mixtures known and every speciation method relies
      on a simplification of their complexity. Argentation chromatography is shown to
      be superior to traditional liquid chromatographic ways of separating aromatic
      compounds based on the number of aromatic carbon atoms. A silver(I)
      mercaptopropano silica gel allows an efficient group separation of polycyclic
      aromatic compounds to be achieved. The usefulness of this phase is demonstrated
      for SRM 1582 Wilmington crude oil and a diesel fuel. Furthermore, the phase can
      also be used for semi-preparative purposes to collect fractions for further
      analysis with high resolution mass spectrometry. Orbitrap mass spectra are
      obtained here for the polycyclic aromatic sulfur heterocycles and it is
      demonstrated that they can contain one to five naphtheno rings.

PMID- 22153207
TI  - [Decision basis for the choice of health care provider].

PMID- 22153208
TI  - [Antioxidants and male subfertility--a survey of a Cochrane review].
AB  - In a Cochrane review the authors suggest that treatment with antioxidant
      supplementation in subfertile men may improve the outcome of live birth and
      pregnancy rate for infertile couples undergoing assisted reproductive technology
      cycles. We disagree as publication bias cannot be excluded and most studies were
      designed to investigate the effects of antioxidant treatment on semen quality. In
      addition, the men were treated with many different combinations and doses of
      antioxidants and it is not possible to recommend infertile men on type and dose
      of antioxidant. Future studies should be large, randomized placebo-controlled
      trials.

PMID- 22153209
TI  - [Limited evidence of the effect of prophylactic pelvic floor training on genital
      prolapse].
AB  - A growing number of women are bothered by genital prolapse. The treatment of
      genital prolapse includes pelvic floor exercise in variable extent, but only few
      data are published. Variations in interventions, follow-up time, outcome etc.
      complicates a comparison. Because of the very limited material it is difficult to
      conclude if pelvic floor exercises have any effect on genital prolapse. There is
      need for studies concerning the clinical relevance and a cost-benefit analysis.

PMID- 22153210
TI  - [Aminopyridines for symptomatic treatment of multiple sclerosis].
AB  - 3,4-diaminopyridine (DAP) and 4-aminopyridine (AP) block potassium channels and
      can improve action potentials in demyelinated nerve fibres. We identified ten
      randomised placebo-controlled trials investigating AP/DAP as symptomatic
      treatment in multiple sclerosis. There is evidence that AP and DAP improve muscle
      strength in the lower extremities and that AP increases walking speed, and it
      might improve Expanded Disability Status Scale scores, spasticity and fatigue.
      There is a lack of evidence-based guidelines of treatment and studies
      investigating the effect on participation/activity and quality of life.

PMID- 22153211
TI  - [Iodine fortification of salt and thyroid disease in Denmark].
AB  - Until 2000 Denmark was iodine deficient with moderate deficiency in the western
      part and mild deficiency in the eastern part. The occurrence of goitre and
      autonomous hyperthyroidism was high, and pregnancy was associated with a
      reduction in thyroid function. After cautious mandatory iodization of household
      salt and salt used for bread production, the iodine intake in Denmark is now low
      normal. The DanThyr monitoring has shown a transient increase in hyperthyroidism
      followed by a decrease, and goitre is becoming less common. Hypothyroidism has
      become more common, and this has to be followed.

PMID- 22153212
TI  - [Acute phosphate nephropathy as a complication to bowel cleansing with oral
      sodium phosphate].
AB  - Acute phosphate nephropathy (APhN) has recently been identified as a reason for
      acute and subsequently chronic renal failure, following exposure to the oral
      sodium phosphate bowel purgatives. Renal biopsies show acute and chronic tubular
      injury with calcium phosphate deposits. A case of biopsy-proven APhN is
      described. The choice of bowel purgatives should be individualised with respect
      to the risk factors for development of APhN.

PMID- 22153213
TI  - [Acrodermatitis chronica atrophicans can be difficult to diagnose].
AB  - A healthy 29 year-old man developed over four years a slowly increasing swelling
      and violet discolouring of the third toe on his left foot. He was examined by
      several specialists and an amputation was recommended since the condition was
      unknown and aggravating. On suspicion of Borrelia infection the patient was
      prescribed penicillin treatment for 28 days with convincing effect. Serologic
      tests showed increased Borrelia titer. Biopsy showed chronic inflammation without
      any suspicion of malignity. Denmark is endemic for borreliosis and per year
      approximately 50 cases develop acrodermatitis chronic atrophicans.

PMID- 22153214
TI  - [Subphrenic Meckel's diverticulum as a differential diagnosis to Chilaiditi's
      syndrome].
AB  - Meckel's diverticulum (MD) occurs in 2-4% of the population and is the most
      common congenital abnormality of the gastrointestinal tract. A 67 year-old woman
      was admitted with acute abdomen. Abdominal X-ray showed pneumoperitoneum. During
      explorative laparoscopy a large perforated MD was found over the right hepatic
      lobe. CT-scans from an earlier admission revealed the MD but it was
      misinterpreted on that occasion. An MD in this place and in a person of this age
      is extremely rare. This case can primarily serve as differential diagnosis when
      CT-scans reveal mysterious subphrenic configurations.

PMID- 22153215
TI  - [Gallstone ileus of the colon].
AB  - Gallstone is a rare cause of large bowel obstruction. The condition is mainly
      reported in elderly women with considerable comorbidity and hence with high
      morbidity and mortality. We describe a case of a 75 year-old woman, with known
      gallbladder stone, presenting with symptoms of large bowel obstruction. Computed
      tomography of the abdomen confirmed a large gallstone obstructing the colon. The
      gallstone was subsequent removed by cololithotomi and the patient made a full
      recovery.

PMID- 22153216
TI  - Decision-making in the end-of-life phase of high-grade glioma patients.
AB  - BACKGROUND: During the disease course of high-grade glioma (HGG) patients, the
      goal of therapy eventually shifts from primarily life-prolongation to primarily
      sustaining the quality of life as good as possible. End-of-life care is aimed at
      prolongation of life with good quality, but inevitably also may require medical
      decisions for prevention and relief of suffering with a potential life shortening
      effect. Few data are available on this end-of-life decision (ELD) making process
      in HGG patients, with decreased consciousness, confusion or cognitive deficits
      preventing them to participate. In this study the ELD-making process in HGG
      patients is described. METHODS: Physicians and relatives of a cohort of 155
      deceased HGG patients were identified to fill in a questionnaire regarding the
      end-of-life conditions (patients' ELD preferences, patients' competence) and ELD
      making (forgoing treatment and the administration of drugs with a potential life
      shortening effect) for their patient or relative. Data were analysed with
      descriptive statistics. FINDINGS: Of 101 patients, physicians completed surveys
      including questions about ELDs (62% response rate). More than half of the
      patients relatively early became incompetent to make decisions due to delirium,
      cognitive deficits and/or decreasing consciousness. In 40% of patients the
      physician did not discuss ELD preferences with his/her patient. At least one ELD
      was made in 72% of patients, most often this comprised the withdrawal of
      dexamethasone. Palliative sedation was performed in 30% of patients and physician
      assisted death in 7%. INTERPRETATION: ELDs are common practises amongst HGG
      patients, although their preferences towards ELDs are frequently unknown to the
      physician. Because the majority of patients become incompetent towards death,
      participation in ELD-making is only possible with advanced care planning. Hence,
      timely discussion of ELD preferences is encouraged.

PMID- 22153217
TI  - Hepatectomy and resection of concomitant extrahepatic disease for colorectal
      liver metastases--a systematic review.
AB  - BACKGROUND: Recent data suggest that hepatectomy for patients with colorectal
      liver metastases (CLM) with concomitant extrahepatic disease (EHD) achieve
      encouraging survival result. The authors examine the clinical efficacy of this
      treatment approach through a systematic review of the published literature.
      METHODS: Electronic search of the MEDLINE and PubMed databases (January 2000 to
      January 2011) to identify studies reporting outcomes of hepatectomy for CLM with
      resection of EHD was undertaken. Two reviewers independently appraised each study
      using a predetermined protocol. Clinical efficacy was synthesised through a
      narrative review with full tabulation of results of all included studies.
      RESULTS: Twenty-two studies were examined. This comprised 1142 patients. The
      median disease-free survival was 12 (range, 4-22) months, median overall survival
      was 30 (range, 14-44) months and median 5-year survival rate was 19% (range, 0
      42%). Median 5-year survival of patients with R0 hepatectomy with resection of
      EHD was 25% (range, 19-36%). Survival based on site of EHD include lung; median
      survival (M/S) was 41 (range, 32-46) months, porto-caval lymph node; M/S was 25
      (range, 19-48) months, peritoneal metastases; M/S was 25 (range, 18-32) months.
      CONCLUSION: In the era of effective systemic therapies, surgical resection of CLM
      and concomitant EHD in carefully selected patients may achieve survival results
      superior to non-surgically treated patients. This treatment strategy may be
      considered appropriate especially when a R0 hepatectomy and complete resection of
      EHD may be achieved.

PMID- 22153218
TI  - Current and future aspects of nuclear molecular therapies: a model of
      theranostics.

PMID- 22153219
TI  - Potential inadequacy of automatic tube compensation to decrease inspiratory work
      load after at least 48 hours of endotracheal tube use in the clinical setting.
AB  - BACKGROUND: Endotracheal tubes (ETTs) impose a substantial respiratory work load
      on mechanically ventilated patients. Automatic tube compensation (ATC) should
      overcome this flow-dependent resistive work load; however, ETT resistance can be
      increased by tracheal secretions or ETT deformities.  Our bench study
      investigated whether ATC provides effective respiratory work load relief in used
      ETTs. METHODS: We enrolled 20 critically ill patients requiring mechanical
      ventilation for longer than 48 hours. After extubation, we collected the used
      ETTs and measured the pressure-time products  (PTPs) by using a bellows-in-a-box
      lung model that simulated spontaneous breathing, at a respiratory rate of 10
      breaths/min, inspiratory time of 1.0 s, and tidal volumes (V(T)) of 300 mL, 500
      mL, and 700 mL. The ventilator was set at ATC 100% with PEEP of 5 cm H(2)O and
      F(IO(2))  of 0.21. The flow and airway pressure at the proximal (P(aw)) and
      distal (P(tr)) ends of the ETT were recorded, and the PTP integrated from P(tr)
      analyzed. RESULTS: PTP values increased with V(T) during ATC. Even at 100% ATC
      the ventilator did not completely  compensate for the PTP imposed by the ETT. In
      used ETTs, peak flow and peak P(aw) were lower and PTP values were greater than
      in new ETTs. As V(T) increased, the percentage difference in the PTP values
      between the new and used ETTs increased. CONCLUSIONS: ATC does not necessarily 
      compensate for an ETT-imposed respiratory work load. ETT configuration changes
      and tracheal secretions can increase ETT resistance and decrease the ability of
      ATC to compensate for the increased respiratory work load.

PMID- 22153220
TI  - The impact of complex survey design on prevalence estimates of intakes of food
      groups in the Australian National Children's Nutrition and Physical Activity
      Survey.
AB  - OBJECTIVE: To assess the impact of the complex survey design used in the 2007
      Australian National Children's Nutrition and Physical Activity Survey (ANCNPAS07)
      on prevalence estimates for intakes of groups of foods in the population of
      children. DESIGN: The impacts on prevalence estimates were determined by
      calculating design effects for values for food group consumption. The
      implications of ignoring elements of the sample design including stratification,
      clustering and weighting are discussed. SETTING: The ANCNPAS07 used a complex
      sample design involving stratification, a high degree of clustering and
      estimation weights. SUBJECTS: Australian children aged 2-16 years. RESULTS:
      Design effects ranging from <1 to 5 were found for the values of mean consumption
      and proportion of the population consuming the food groups. When survey weights
      were ignored, prevalence estimates were also biased. CONCLUSIONS: Ignoring the
      complex survey design used in the ANCNPAS07 could result in underestimating the
      width of confidence intervals, higher mean square errors and biased estimators.
      The magnitude of these effects depends on both the parameter under consideration
      and the chosen estimator.

PMID- 22153221
TI  - Annulus tension of the prolapsed mitral valve corrected by edge-to-edge repair.
AB  - BACKGROUND: Mitral valve (MV) performance after edge-to-edge repair (ETER)
      without ring annuloplasty is suboptimal. ETER efficacy needs to be evaluated from
      annulus tension (AT) of a prolapsed MV corrected by ETER to understand annular
      dilatation. METHODS: Ten porcine MVs were harvested and mounted on a MV closure
      test rig. The MV annulus tissue rested on top of a saddle-shaped plastic ring on
      which the annulus could slide freely. The annulus was held by strings in the
      periphery during MV closure under a hydrostatic trans-mitral pressure. String
      tensions were measured and further divided by string spacing to obtain AT. The
      MVs were then prolapsed by shifting split papillary muscles to simulate mono
      leaflet prolapse due to elongation of chords, which insert into a single leaflet.
      Last, MV prolapse was corrected by ETER applied in the central leaflet region and
      AT was measured. RESULTS: AT in both anterior and posterior leaflet prolapse
      corrected by ETER was less than that of normal MVs. AT in the anterior leaflet
      prolapse corrected by ETER was less than that in the posterior leaflet prolapse
      corrected by ETER. CONCLUSION: ETER does not restore the normal AT and therefore
      leads potential of annular dilatation. The anterior leaflet prolapse has a
      greater potential of annular dilatation than the posterior leaflet prolapse after
      ETER. Annuloplasty is recommended to maintain long-term ETER efficacy.

PMID- 22153222
TI  - Effect of the fluid-structure interactions on low-density lipoprotein transport
      within a multi-layered arterial wall.
AB  - The effects of fluid-structure interactions (FSI) and pulsation on the transport
      of low-density lipoprotein (LDL) through an arterial wall are analyzed in this
      work. To this end, a comprehensive multi-layer model for both LDL transport as
      well as fluid-structure interaction (FSI) is introduced. The constructed model is
      analyzed and compared with the existing results in the limiting cases. Excellent
      agreement is found between the presented model and the existing results in the
      limiting cases. The presented model takes into account the complete multi-layered
      LDL transport while incorporating the FSI aspects to enable a comprehensive study
      of the deformation effect on the pertinent parameters of the transport processes
      within an artery. Since the flow inside an artery is time-dependent, the impact
      of pulsatile flow is also analyzed with and without FSI. A detailed analysis is
      presented to illustrate the consequence of different factors on the LDL transport
      in an artery.

PMID- 22153223
TI  - Evaluation of deformable image coregistration in adaptive dose painting by
      numbers for head-and-neck cancer.
AB  - PURPOSE: To assess the accuracy of contour deformation and feasibility of dose
      summation applying deformable image coregistration in adaptive dose painting by
      numbers (DPBN) for head and neck cancer. METHODS AND MATERIALS: Data of 12 head
      and-neck-cancer patients treated within a Phase I trial on adaptive (18)F-FDG
      positron emission tomography (PET)-guided DPBN were used. Each patient had two
      DPBN treatment plans: the initial plan was based on a pretreatment PET/CT scan;
      the second adapted plan was based on a PET/CT scan acquired after 8 fractions.
      The median prescription dose to the dose-painted volume was 30 Gy for both DPBN
      plans. To obtain deformed contours and dose distributions, pretreatment CT was
      deformed to per-treatment CT using deformable image coregistration. Deformed
      contours of regions of interest (ROI(def)) were visually inspected and, if
      necessary, adjusted (ROI(def_ad)) and both compared with manually redrawn ROIs
      (ROI(m)) using Jaccard (JI) and overlap indices (OI). Dose summation was done on
      the ROI(m), ROI(def_ad), or their unions with the ROI(def). RESULTS: Almost all
      deformed ROIs were adjusted. The largest adjustment was made in patients with
      substantially regressing tumors: ROI(def) = 11.8 +/- 10.9 cm(3) vs. ROI(def_ad) =
      5.9 +/- 7.8 cm(3) vs. ROI(m) = 7.7 +/- 7.2 cm(3) (p = 0.57). The swallowing
      structures were the most frequently adjusted ROIs with the lowest indices for the
      upper esophageal sphincter: JI = 0.3 (ROI(def)) and 0.4 (ROI(def_ad)); OI = 0.5
      (both ROIs). The mandible needed the least adjustment with the highest indices:
      JI = 0.8 (both ROIs), OI = 0.9 (ROI(def)), and 1.0 (ROI(def_ad)). Summed doses
      differed non-significantly. There was a trend of higher doses in the targets and
      lower doses in the spinal cord when doses were summed on unions. CONCLUSION:
      Visual inspection and adjustment were necessary for most ROIs. Fast automatic ROI
      propagation followed by user-driven adjustment appears to be more efficient than
      labor-intensive de novo drawing. Dose summation using deformable image
      coregistration was feasible. Biological uncertainties of dose summation
      strategies warrant further investigation.

PMID- 22153224
TI  - Efficacy and safety of peginterferon alfa-2b plus ribavirin for HCV-positive
      mixed cryoglobulinemia: a multicentre open-label study.
AB  - OBJECTIVES: The aim of the present study is to provide information on clinical
      outcome of the patients affected by HCV-positive mixed cryoglobulinemia (MC)
      treated with PEG-IFN and Ribavirin for 6 or 12 months according to the HCV
      genotype. METHODS: Eighty-six patients (42 women and 44 men) were enrolled in 8
      Italian centres. All the patients had MC in the active phase of the disease. The
      patients received Peginterferon alfa-2b 1.5 mcg/kg/once a week (QW) and daily
      oral Ribavirin (800/1,000/1,200) according to their body weight for 48 weeks for
      genotype 1 and 4 and for 24 weeks for genotypes 2 and 3. RESULTS: In the 44
      patients who underwent 12 months of therapy, 17 cases (39%) could be considered
      as 'non-responders' and 11 relapsed, therefore only 16 patients (36%) obtained a
      sustained virological response. In the 42 patients who underwent six months of
      therapy only 7 cases (17%) could be considered as 'non-responders' and 8
      relapsed, therefore 27 patients (64%) obtained a sustained virological response.
      Purpura score dropped in both group (p<5.79 x 10-17) and only 5 cases of the
      group A (11%) and 5 of the group B (12%) did not show any improvement.
      Arthralgias showed a similar behaviour. Many patients relapsed after the end of
      the treatment. CONCLUSIONS: This study documents a lower response rate than that
      observed in the clinical trials with HCV chronic hepatitis, but the presence of
      comorbidities and older age should be taken into consideration. Most patients
      (88.5%) showed a complete and persistent recovery from clinical symptoms.

PMID- 22153225
TI  - Predicting persistent alcohol problems: a prospective analysis from the Great
      Smoky Mountain Study.
AB  - BACKGROUND: Rates of alcohol disorders peak in late adolescence and decrease
      substantially into the mid-20s. Our aim was to identify risk factors that predict
      alcohol problems that persist into the mid-20s. METHOD: Data are from the
      prospective, population-based Great Smoky Mountains Study (GSMS; n=1420), which
      followed children through late adolescence and into young adulthood. Alcohol
      persisters were defined as subjects with an alcohol disorder (abuse or
      dependence) in late adolescence (ages 19 and 21 years) that continued to meet
      criteria for an alcohol disorder at the mid-20s assessment. RESULTS: The 3-month
      prevalence of having an alcohol disorder (abuse or dependence) decreased markedly
      from late adolescence into the mid-20s. A third of late adolescents with an
      alcohol disorder continued to meet criteria for an alcohol disorder in young
      adulthood (37 of 144 who met criteria in late adolescence). Risk factors for
      persister status included multiple alcohol abuse criteria during late adolescence
      but no alcohol dependence criteria. Risk factors for persister status also
      included associated features of alcohol dependence such as craving alcohol and
      drinking to unconsciousness. Persister status was also associated with
      depression, cannabis dependence and illicit substance use, but not with other
      psychiatric disorders. More than 90% of late adolescents with three or more of
      the risk factors identified met criteria for a young adult alcohol disorder.
      CONCLUSIONS: Symptoms of alcohol abuse, not dependence, best predict long-term
      persistence of alcohol problems. The set of risk factors identified may be a
      useful screen for selective and indicated prevention efforts.

PMID- 22153226
TI  - Preparation of nanocrystalline cellulose via ultrasound and its reinforcement
      capability for poly(vinyl alcohol) composites.
AB  - Rod-shaped nanocrystalline cellulose (NCC) was prepared from microcrystalline
      cellulose (MCC) using the purely physical method of high-intensity
      ultrasonication. Scanning electron microscopy, transmission electron microscopy,
      and X-ray diffraction was used for the characterization of the morphology and
      crystal structure of the material. The thermal properties were investigated using
      thermogravimetric analysis. The reinforcement capabilities of the obtained NCC
      were investigated by adding it to poly(vinyl alcohol) (PVA) via the solution
      casting method. The results revealed that the prepared NCC had a rod-shaped
      structure, with diameters between 10 and 20 nm and lengths between 50 and 250 nm.
      X-ray diffraction results indicated that the NCC had the cellulose I crystal
      structure similar to that of MCC. The crystallinity of the NCC decreased with
      increasing ultrasonication time. The ultrasonic effect was non-selective, which
      means it can remove amorphous cellulose and crystalline cellulose. Because of the
      nanoscale size and large number of free-end chains, the NCC degraded at a
      slightly lower temperature, which resulted in increased char residue (9.6-16.1%),
      compared with that of the MCC (6.2%). The storage modulus of the nanocomposite
      films were significantly improved compared with that of pure PVA films. The
      modulus of PVA with 8 wt.% NCC was 2.40* larger than that of pure PVA.

PMID- 22153227
TI  - Comparison of energy consumptions between ultrasonic, mechanical, and combined
      soil washing processes.
AB  - Vigorous physical effects including micro-jet and micro-streaming can be induced
      in heterogeneous systems by acoustic cavitation. This can be useful for the
      removal of pollutants from contaminated soil particles. In this study, the diesel
      removal efficiencies in ultrasonic, mechanical, and combined soil washing
      processes have been compared considering the electrical energy consumptions for
      these processes. The combined process showed synergistic effects for both removal
      efficiency and effective volume also has the advantage of a short operation time
      compared to the sequential processes. Thus the ultrasonic soil washing process
      with mechanical mixing is considered a promising technology for industrial use.

PMID- 22153228
TI  - Synergistic bactericidal effects and mechanisms of low intensity ultrasound and
      antibiotics against bacteria: a review.
AB  - Low intensity ultrasonic therapy is always an important research area of
      ultrasonic medicine. This review concentrates on low intensity ultrasound
      enhancing bactericidal action of antibiotics against bacteria in vitro and in
      vivo, including planktonic bacteria, bacterial biofilms, Chlamydia, and bacteria
      in implants. These literatures show that low intensity ultrasound alone is not
      effective in killing bacteria, while the combination of low intensity ultrasound
      and antibiotics is promising. Low intensity ultrasound facilitating antibiotic
      treatment is still in its infancy, and still requires a great deal of research in
      order to develop the technology on medical treatment scale.

PMID- 22153230
TI  - Neuroradiological findings and clinical features of fourth-ventricular
      meningioma: a study of 10 cases.
AB  - AIM: To present the neuroradiological and clinical findings of fourth-ventricular
      meningiomas to increase awareness of this entity. MATERIALS AND METHODS: The
      computed tomography (CT; n=5), magnetic resonance imaging (MRI; n=9) features and
      clinical presentations of 10 patients with pathologically documented fourth
      ventricular meningiomas were retrospectively analysed. RESULTS: All tumours
      appeared as well-demarcated masses in the fourth ventricle at CT and MRI. The
      tumour shape was round in eight cases (80%) and irregular in two cases (20%). The
      CT images of five cases showed predominantly isoattenuation in three cases and
      high attenuation in two cases, with a mean attenuation value of 52 HU. In
      addition, calcifications were seen in three cases. At MRI, nine masses were
      isointense (n=6) or hypointense (n=3) to grey matter on T1-weighted images and
      mildly hyperintense (n=4), isointense (n=3), hypointense (n=1), and of mixed
      signal intensity (n=1) on T2-weighted and fluid-attenuated inversion recovery
      (FLAIR) images. Signal voids were visible in two cases. Enhancement after
      injection of contrast material was marked homogeneous (n=5) or heterogeneous
      (n=5) on CT or T1-weighted images. Three tumours had mild peritumoural oedema.
      Three tumours were associated with obstructive hydrocephalus. The pathological
      subtype of the 10 meningiomas was fibromatous (n=5), atypical (n=2), and one each
      of transitional, psammomatous, and clear-cell type. CONCLUSION: Although fourth
      ventricular meningioma is quite rare, it should be considered in differential
      diagnosis of neoplasms within the fourth ventricle. The relatively typical
      radiological appearance, combined the age and sex of patients, can suggest the
      diagnosis of fourth-ventricular meningioma.

PMID- 22153231
TI  - Serum alpha-fetoprotein response can predict prognosis in hepatocellular
      carcinoma patients undergoing radiofrequency ablation therapy.
AB  - AIMS: To evaluate the clinical inference of serum alpha-fetoprotein (AFP)
      response in hepatocellular carcinoma (HCC) patients undergoing percutaneous
      radiofrequency ablation (RFA). MATERIALS AND METHODS: Three hundred and thirteen
      previously untreated HCC patients were enrolled in the study. The optimal AFP
      response was defined as >20% decrease from baseline after 1 month of RFA for
      those with a baseline AFP level of >=100 ng/ml. The impact of AFP response on
      prognosis was analysed and prognostic factors were assessed. RESULTS: After a
      median follow-up of 26.7 +/- 19.1 months, 49 patients died and 264 patients were
      alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with
      an initial AFP of <100 ng/ml and >=100 ng/ml, respectively (p = 0.003). In the 58
      patients with a baseline AFP of >=100 ng/ml and initial completed tumour necrosis
      after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal
      and non-optimal AFP responders, respectively (p = 0.001). By multivariate
      analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009),
      non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were
      independent risk factors predictive of poor overall survival. Besides, the
      cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal
      AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated
      platelet count <=10(5)/mm(3) (p = 0.048), tumour size >2 cm (p = 0.027), and non
      optimal AFP response (p < 0.001) were independent risk factors associated with
      tumour recurrence after RFA. CONCLUSIONS: Serum AFP response may be a useful
      marker for predicting prognosis in HCC patients undergoing RFA.

PMID- 22153232
TI  - Magnetic navigation in ultrasound-guided interventional radiology procedures.
AB  - AIM: To evaluate the usefulness of magnetic navigation in ultrasound (US)-guided
      interventional procedures. MATERIALS AND METHODS: Thirty-seven patients who were
      scheduled for US-guided interventional procedures (20 liver cancer ablation
      procedures and 17 other procedures) were included. Magnetic navigation with three
      dimensional (3D) computed tomography (CT), magnetic resonance imaging (MRI), 3D
      US, and position-marking magnetic navigation were used for guidance. The
      influence on clinical outcome was also evaluated. RESULTS: Magnetic navigation
      facilitated applicator placement in 15 of 20 ablation procedures for liver cancer
      in which multiple ablations were performed; enhanced guidance in two small liver
      cancers invisible on conventional US but visible at CT or MRI; and depicted the
      residual viable tumour after transcatheter arterial chemoembolization for liver
      cancer in one procedure. In four of 17 other interventional procedures, position
      marking magnetic navigation increased the visualization of the needle tip.
      Magnetic navigation was beneficial in 11 (55%) of 20 ablation procedures;
      increased confidence but did not change management in five (25%); added some
      information but did not change management in two (10%); and made no change in two
      (10%). In the other 17 interventional procedures, the corresponding numbers were
      1 (5.9%), 2 (11.7%), 7 (41.2%), and 7 (41.2%), respectively (p=0.002).
      CONCLUSION: Magnetic navigation in US-guided interventional procedure provides
      solutions in some difficult cases in which conventional US guidance is not
      suitable. It is especially useful in complicated interventional procedures such
      as ablation for liver cancer.

PMID- 22153233
TI  - Early signaling network in tobacco cells elicited with methyl jasmonate and
      cyclodextrins.
AB  - We analyze, for the first time, the early signal transduction pathways triggered
      by methyl jasmonate (MJ) and cyclodextrins (CDs) in tobacco (Nicotiana tabacum)
      cell cultures, paying particular attention to changes in cytosolic free Ca(2+)
      concentration ([Ca(2+)](cyt)), the production of hydrogen peroxide (H(2)O(2)) and
      nitric oxide (NO), and late events like the induction of capsidiol. Our data
      indicate that MJ and CDs trigger a [Ca(2+)](cyt) rise promoted by Ca(2+) influx
      through Ca(2+)-permeable channels. The joint presence of MJ and CDs provokes a
      first increase in [Ca(2+)](cyt) similar to that observed in MJ-treated cells,
      followed by a second peak similar to that found in the presence of CDs alone.
      Moreover, oxidative burst induced by MJ is more pronounced when tobacco cells are
      incubated with CDs alone or in combination with MJ. The presence of both
      elicitors provokes H(2)O(2) production similar to that found in CD-treated cells,
      and a sustained response similar to that found in MJ-treated cells. In all
      treatments, H(2)O(2) production is dependent on Ca(2+) influx and protein
      phosphorylation events. Similarly, the joint action of both elicitors provokes NO
      accumulation, although to a lesser extent that in MJ-treated cells because CDs
      alone do not trigger this accumulation. This NO production is dependent on Ca(2+)
      influx but independent of both H(2)O(2) production and staurosporine-sensitive
      phosphorylation events. Taken as a whole, these results suggest the existence of
      different intracellular signaling pathways for both elicitors. Likewise, CDs
      might act by regulating the signaling pathway triggered by MJ since, in the
      presence of both compounds, CDs neutralize the strong oxidative and nitrosative
      bursts triggered by MJ and therefore, they regulate both H(2)O(2) and NO levels.

PMID- 22153234
TI  - Phytochromes A and C cooperatively regulate early and transient gene expression
      after red-light irradiation in rice seedlings.
AB  - Phytochromes are red/far-red photoreceptors encoded by a small gene family in
      higher plants. Differences in phenotype among mutants suggest distinct functions
      among phytochrome subfamilies. We attempted to find distinct functions among
      phytochromes by oligo-microarray analysis of single, double, and triple mutants
      in rice. In most cases, gene expression was redundantly regulated by phytochromes
      A and B after irradiation by a red light pulse in etiolated rice shoots. However,
      we found that several genes were specifically regulated by phytochromes A and C.
      Most of them were expressed immediately after the red light pulse in a transient
      manner. They are stress-related genes that may be involved in resistance to light
      stress when etiolated seedlings are exposed to light. These genes were not
      expressed in green leaves after the red light pulse, suggesting that they have a
      function specific to etiolated seedlings.

PMID- 22153235
TI  - Silencing of flavanone-3-hydroxylase in apple (Malus * domestica Borkh.) leads to
      accumulation of flavanones, but not to reduced fire blight susceptibility.
AB  - Transgenic antisense flavanone-3-hydroxylase apple plants were produced to mimic
      the effect of the agrochemical prohexadione-Ca on apple leaves. This enzyme
      inhibitor for 2-oxoglutarate dependent dioxygenases is used as a growth retardant
      and for control of secondary fire blight of leaves. Like using the agent,
      silencing of flavanone-3-hydroxylase leads to an accumulation of flavanones in
      leaves, but in contrast not to the formation of 3-deoxyflavonoids. In
      prohexadione-Ca treated leaves the 3-deoxyflavonoid luteoforol is formed from
      accumulating flavanones, acting as an antimicrobial compound against the fire
      blight pathogen Erwinia amylovora. Seemingly, the silencing of just one of the 2
      oxoglutarate dependent dioxygenases (in apple also flavonol synthase and
      anthocyanidin synthase take part downstream in the pathway) does not provide a
      sufficiently high ratio of flavanones to dihydroflavonols. This seems to be
      needed to let the dihydroflavonol-4-reductase/flavanone-4-reductase enzyme reduce
      flavanones to luteoforol, and to let this be reduced by the leucoanthocyanidin-4
      reductase/3-deoxyleucoanthocyanidin-4-reductase, each acting with their
      respective weak secondary activities. Accordingly, also the intended inducible
      resistance to fire blight by prohexadione-Ca is not observed with the antisense
      flavanone-3-hydroxylase apple plants. On the other hand, for most transgenic
      lines with strong flavanone-4-reductase down-regulation, up-regulation of gene
      expression for the other flavonoid genes was found. This provides further
      evidence for the feedback regulation of flavonoid gene expression having been
      previously reported for the prohexadione-Ca inhibited apple plants.

PMID- 22153236
TI  - NADPH oxidase in plasma membrane is involved in stomatal closure induced by
      dehydroascorbate.
AB  - Stoma is surrounded by two guard cells, and regulates the contents of water and
      CO(2) in plant, its opening and closing was affected by various factors.
      Recently, dehydroascorbate was found to induce stomata closure and H(2)O(2)
      generation. However, the mechanism of H(2)O(2) production is not clear. DPI and
      imidazole inhibit the flavoprotein and the b(-type) cytochrome components of the
      NADPH oxidase complex. Application of DPI or imidazole with DHA together impaired
      stomatal closure and elevation of H(2)DCF-DA fluorescent intensity induced by DHA
      in guard cells. CoCl(2) and PD98059, as the blocker of calcium channel and the
      inhibitor of MAPKKK, both impaired stomatal closure induced by DHA. The results
      suggested that DHA-induced H(2)O(2) generation via activation of NADPH oxidase,
      and thus resulting in stomatal closure. Moreover, Ca(2+) channel and MAPK
      cascades were involved in stomatal closure induced by DHA.

PMID- 22153237
TI  - Arabidopsis long-chain acyl-CoA synthetase 1 (LACS1), LACS2, and LACS3 facilitate
      fatty acid uptake in yeast.
AB  - The plant cuticle is a lipid-based barrier on the aerial surfaces of plants that
      plays a variety of protective roles. The cuticle is comprised largely of long
      chain and very-long-chain fatty acids and their derivatives. In Arabidopsis, LONG
      CHAIN ACYL-COA SYNTHETASE1 (LACS1), LACS2, and LACS3 are known or suspected
      cuticle biosynthetic genes. Very-long-chain acyl-coenzyme A (CoA) synthetase
      activity has been demonstrated for LACS1 and LACS2, although the role for such an
      activity in cuticle biosynthesis is currently unclear. In yeast and mammalian
      systems, some very-long-chain acyl-CoA synthetases are also called fatty acid
      transport proteins (FATPs) due to a second function of mediating transmembrane
      movement of fatty acids. We sought to determine if LACS1-3 also have this dual
      functionality. A yeast fat1Delta mutant is deficient in both very-long-chain acyl
      CoA synthetase activity and exogenous fatty acid uptake. We demonstrate that
      heterologous expression of LACS1, 2, or 3 is able to complement both of these
      deficiencies. Furthermore, expression of each LACS enzyme in yeast resulted in
      uptake of the long-chain fatty acid analogue, C(1)-BODIPY-C(12). Only expression
      of LACS1 resulted in uptake of the very-long-chain fatty acid analogue, BODIPY
      C(16). These results demonstrate that LACS1, LACS2, and LACS3 have the dual
      functionality of yeast and mammalian FATP enzymes. These findings have
      implications in the transmembrane transport and intracellular trafficking of
      plant lipids destined for export to the cuticle.

PMID- 22153238
TI  - SA improvement of hyperhydricity reversion in Thymus daenensis shoots culture may
      be associated with polyamines changes.
AB  - In shoot cultures of Thymus daenensis, hyperhydricity syndrome promoted by
      benzyladenine (BA) is characterised by the development of chlorophyll-deficient
      shoots with a high water content and reduced growth that is less differentiated.
      By removing the BA from the culture medium, the hyperhydricity was reversed, and
      the reversion toward a normal growth in vitro was more efficient in shoots
      treated with 5 MUM of salicylic acid (SA), showing a significant increase in
      chlorophyll b after 4 weeks of culture. In the present study, the effect of
      salicylic acid on the reversion of shoot hyperhydricity was investigated at the
      level of the free, soluble and insoluble conjugated polyamine content. In T.
      daenensis micropropagated shoots, the level of polyamines was high, with a
      predominance of putrescine. BA, which triggered hyperhydricity, caused a
      reduction of the polyamine (PA) content by one-half due to a decrease in the
      putrescine content and insoluble conjugated PAs that were not detected in the
      hyperhydric shoots. In the reverted shoots, changes of the free polyamines,
      spermidine and, more notably, spermine, were shown. The spermine content doubled
      after 4 weeks of culture, and its amount was the same as that found in normal
      shoots, suggesting that free spermine could be particularly involved in the
      reversion of hyperhydricity. In the SA-reverted tissues, the PA pattern was
      marked with a transient increase of free putrescine, spermidine and spermine and
      an enhancement of soluble conjugated spermine. This transitory SA-dependent
      amplification of PAs was concomitant with a remarkable transient increase of
      H(2)O(2), suggesting that SA may be implicated in PA signalling pathways for
      tissue differentiation during the reversion of hyperhydricity in T. daenensis.

PMID- 22153239
TI  - Multiple compartmentalization of sodium conferred salt tolerance in Salicornia
      europaea.
AB  - Euhalophyte Salicornia europaea L., one of the most salt-tolerant plant species
      in the world, can tolerate more than 1000 mM NaCl. To study the salt tolerance
      mechanism of this plant, the effects of different NaCl concentrations on plant
      growth, as well as Na(+) accumulation and distribution at organ, tissue, and
      subcellular levels, were investigated. Optimal growth and an improved
      photosynthetic rate were observed with the plant treated with 200-400 mM NaCl.
      The Na(+) content in the shoots was considerably higher than that in the roots of
      S. europaea. The Na(+) in S. europaea cells may act as an effective osmotic
      adjuster to maintain cell turgor, promoting photosynthetic competence and plant
      growth. The results from the SEM-X-ray and TEM-X-ray microanalyses demonstrate
      that Na(+) was compartmentalized predominantly into the cell vacuoles of shoot
      endodermis tissues. Accordingly, the transcript amounts of SeNHX1, SeVHA-A, and
      SeVP1 increased significantly with increased NaCl concentration, suggesting their
      important roles in Na(+) sequestration into the vacuoles. Therefore, a multiple
      sodium compartmentalization mechanism is proposed to enhance further the salt
      tolerance of S. europaea.

PMID- 22153240
TI  - Sodium instead of potassium and chloride is an important macronutrient to improve
      leaf succulence and shoot development for halophyte Sesuvium portulacastrum.
AB  - Soil salinity is contributed largely by NaCl but some halophytes such as Sesuvium
      portulacastrum have evolved to adapt salinity environment and demonstrate optimal
      development under moderate salinity. To elucidate the detail mechanisms of the
      great salt tolerance and determine the respective contributions of Na(+), K(+)
      and Cl(-) on the development of S. portulacastrum, morphological and
      physiological analysis were performed using plants supplied with 200 mM of
      different ions including cations (Na(+), K(+), Li(+)) and anions (Cl(-), NO(3)(
      ), Ac(-)) respectively. The results revealed that the salt-treated plants
      accumulated large amounts of sodium in both leaf and stem. There was a greater
      shoot growth in presence of external Na(+) compared to K(+) and Cl(-). Na(+) was
      found more effective than K(+) and Cl(-) in cell expansion, leaf succulence, and
      shoot development. Flame emission and X-Ray microanalysis revealed the relative
      Na(+) content was much higher than K(+) and Cl(-) in both leaf and stem of well
      developed S. portulacastrum, leading to a higher Na(+)/K(+) ratio. The effects of
      different ions on the development of S. portulacastrum were listed as the
      following: Na(+) > NO(3)(-) > CK > Cl(-) > K(+) > Ac(-) > Li(+). These results
      demonstrated NaCl toxicity is attributable largely to the effect of Cl(-) but
      rarely to Na(+), and thus sodium is concluded as a more important macronutrient
      than potassium and chloride for improving leaf succulence and shoot development
      of halophyte S. portulacastrum.

PMID- 22153241
TI  - The Arabidopsis short-chain dehydrogenase/reductase 3, an abscisic acid deficient
      2 homolog, is involved in plant defense responses but not in ABA biosynthesis.
AB  - ABSCISIC ACID DEFICIENT2 (ABA2) encodes a short-chain dehydrogenase/reductase1
      (SDR1) that catalyzes the multi-step conversion of xanthoxin to abscisic aldehyde
      during abscisic acid (ABA) biosynthesis in Arabidopsis thaliana. In this study,
      AtSDR2 and AtSDR3, the two closest homologs to AtABA2, were investigated for
      their potential role in ABA biosynthesis. AtSDR2 showed undetectable
      transcription in plants grown under normal conditions or under stress. AtSDR3 and
      AtABA2 have different spatial and temporal expression patterns. Complementation
      testing demonstrated that the pABA2::SDR3 transgene failed to complement the aba2
      mutant phenotype, and that transgenic plants showed the same levels of ABA as the
      aba2 mutants. These data suggest that AtSDR3 confers no functional redundancy to
      AtABA2 in ABA biosynthesis. Interestingly, microarray data derived from
      Genevestigator suggested that AtSDR3 might have a function that is related to
      plant defense. Pseudomonas syringae pv. tomato (Pst) DC3000 infection and
      systemic acquired resistance (SAR) activator application further demonstrated
      that AtSDR3 plays an important role in plant defense responses at least partially
      through the regulation of AtPR-1 gene expression.

PMID- 22153242
TI  - Identification of hypoxic-responsive proteins in cucumber roots using a proteomic
      approach.
AB  - To elaborate the mechanisms of response of cucumber (Cucumis sativus L. cv.)
      seedlings to hypoxic stress, plants were grown under either normoxic conditions
      or hypoxic stress. As expected, plant biomass was significantly reduced under
      hypoxic stress. Proteomic profiles of cucumber roots were studied at 72 h after
      treatment; 316 and 425 protein spots were detected on polyacrylamide gels from
      normoxic and hypoxic-treated plants, respectively. Compared with normoxic-treated
      plants, protein abundance of 22 proteins was significantly upregulated while
      protein abundance of 12 proteins decreased in the hypoxic-treated plants. Twenty
      one of the proteins whose abundance was altered were identified by MALDI-TOF/TOF
      MS analysis, and categorized into classes corresponding to energy and metabolism
      proteins, transcription factor proteins, defense stress proteins, structural
      proteins and regulatory proteins. Under hypoxic stress, glycolysis was induced;
      energy was channeled to primary metabolism, while secondary pathways and nitrogen
      metabolism pathways were inhibited. Cucumber plants scavenged reactive oxygen
      species by antioxidase, and increased Acyl-[acyl-carrier-protein] desaturase
      which defend against reactive oxygen species damage to plant cell structure. This
      study provides insight that may facilitate a better understanding of the response
      mechanisms of cucumber plant to hypoxic stress.

PMID- 22153243
TI  - Influence of drought stress on the cellular ultrastructure and antioxidant system
      in leaves of drought-tolerant and drought-sensitive apple rootstocks.
AB  - We compared two apple rootstocks -Malus prunifolia and Malus hupehensis - that
      differ in their tolerance to this abiotic stress. The former is considered
      drought-tolerant, the latter, sensitive. We monitored changes in their leaf
      ultrastructure and responses by their antioxidant defense systems. Irrigation was
      withheld for 12 d from two-year-old potted plants. Compared with the control,
      this treatment led to considerable ultrastructural alterations in organelles.
      Plants of M. prunifolia maintained their structural cell integrity longer than
      did M. hupehensis. M. hupehensis was more vulnerable to drought than was M.
      prunifolia, resulting in larger increases in the levels of H(2)O(2), O(2)(-), and
      MDA from the former. Except for catalase (CAT) and monodehydroascorbate reductase
      (MDHAR), the activities of superoxide dismutase (SOD), peroxidase (POD),
      ascorbate peroxidase (APX), glutathione reductase (GR), and dehydroascorbate
      reductase (DHAR) analyzed here were enhanced to a greater extent in M. prunifolia
      than in M. hupehensis in response to drought. This was also true for levels of
      ascorbic acid (AsA) and glutathione (GSH). Under well-watered conditions, changes
      in lipid peroxidation and relevant antioxidant parameters were not significantly
      different between the two species throughout the experimental period. These
      results demonstrate that, in order to minimize oxidative damage, both the
      activities of antioxidant enzymes and antioxidant concentrations are increased in
      the leaves of M. prunifolia and M. hupehensis in response to water stress.
      Moreover, plants of M. prunifolia exhibit higher antioxidant capacity and a
      stronger protective mechanism, such that their cell structural integrity is
      better maintained during exposure to drought.

PMID- 22153244
TI  - Differential expression of salt overly sensitive pathway genes determines
      salinity stress tolerance in Brassica genotypes.
AB  - The objective of the present study was to examine the role of SOS pathway in
      salinity stress tolerance in Brassica spp. An experiment was conducted in pot
      culture with 4 Brassica genotypes, i.e., CS 52 and CS 54, Varuna and T 9
      subjected to two levels of salinity treatments along with a control, viz., 1.65
      (S(0)), 4.50 (S(1)) and 6.76 (S(2)) dS m(-1). Salinity treatment significantly
      decreased relative water content (RWC), membrane stability index (MSI) and
      chlorophyll (Chl) content in leaves and potassium (K) content in leaf, stem and
      root of all the genotypes. The decline in RWC, MSI, Chl and K content was
      significantly less in CS 52 and CS 54 as compared to Varuna and T 9. In contrast,
      the sodium (Na) content increased under salinity stress in all the plant parts in
      all the genotypes, however, the increase was less in CS 52 and CS 54, which also
      showed higher K/Na ratio, and thus more favourable cellular environment. Gene
      expression studies revealed the existence of a more efficient salt overly
      sensitive pathway composed of SOS1, SOS2, SOS3 and vacuolar Na(+)/H(+) antiporter
      in CS 52 and CS 54 compared to Varuna and T 9. Sequence analyses of partial cDNAs
      showed the conserved nature of these genes, and their intra and intergenic
      relatedness. It is thus concluded that existence of an efficient SOS pathway,
      resulting in higher K/Na ratio, could be one of the major factor determining
      salinity stress tolerance of Brassica juncea genotypes CS 52 and CS 54.

PMID- 22153245
TI  - Copper-induced synthesis of ascorbate, glutathione and phytochelatins in the
      marine alga Ulva compressa (Chlorophyta).
AB  - In order to analyze the synthesis of antioxidant and heavy metal-chelating
      compounds in response to copper stress, the marine alga Ulva compressa
      (Chlorophyta) was exposed to 10 MUM copper for 7 days and treated with inhibitors
      of ASC synthesis, lycorine, and GSH synthesis, buthionine sulfoximine (BSO). The
      levels of ascorbate, in its reduced (ASC) and oxidized (DHA) forms, glutathione,
      in its reduced (GSH) and oxidized (GSSG) forms, and phytochelatins (PCs) were
      determined as well as activities of enzymes involved in ASC synthesis, L
      galactose dehydrogenase (GDH) and L-galactono 1,4 lactone dehydrogenase (GLDH),
      and in GSH synthesis, gamma-glutamylcysteine synthase (gamma-GCS) and glutathione
      synthase (GS). The level of ASC rapidly decreased to reach a minimum at day 1
      that remained low until day 7, DHA decreased until day 1 but slowly increased up
      to day 7 and its accumulation was inhibited by lycorine. In addition, GSH level
      increased to reach a maximal level at day 5 and GSSG increased up to day 7 and
      their accumulation was inhibited by BSO. Activities of GDH and GLDH increased
      until day 7 and GLDH was inhibited by lycorine. Moreover, activities of gamma-GCS
      and GS increased until day 7 and gamma-GCS was inhibited by BSO. Furthermore,
      PC2, PC3 and PC4, increased until day 7 and their accumulation was inhibited by
      BSO. Thus, copper induced the synthesis of ascorbate, glutathione and PCs in U.
      compressa suggesting that these compounds are involved in copper tolerance.
      Interestingly, U. compressa is, until now, the only ulvophyte showing ASC, GSH
      and PCs synthesis in response to copper excess.

PMID- 22153246
TI  - Expression of LeNHX isoforms in response to salt stress in salt sensitive and
      salt tolerant tomato species.
AB  - In general, wild tomato species are more salt tolerant than cultivated species, a
      trait that is related to enhanced Na(+) accumulation in aerial parts in the wild
      species, but the molecular basis for these differences is not known. Plant NHX
      proteins have been suggested to be important for salt tolerance by promoting
      accumulation of Na(+) or K(+) inside vacuoles. Therefore, differences in
      expression or activity of NHX proteins in tomato could be at the basis of the
      enhanced salt tolerance in wild tomato species. To test this hypothesis, we
      studied the expression level of four NHX genes in the salt sensitive cultivated
      species Solanum lycopersicum L. cv. Volgogradskij and the salt tolerant wild
      species Solanum pimpinelifolium L in response to salt stress. First, we
      determined that in the absence of salt stress, the RNA abundance of LeNHX2, 3 and
      4 was comparable in both species, while more LeNHX1 RNA was detected in the
      tolerant species. LeNHX2 and LeNHX3 showed comparable expression levels and were
      present in all tissues, while LeNHX4 was expressed above all in stem and fruit
      tissues. Next, we confirmed that the wild species was more tolerant and
      accumulated more Na(+) in aerial parts of the plant. This correlated with the
      observation that salt stress induced especially the LeNHX3 and LeNHX4 isoforms in
      the tolerant species. These results support a role of NHX genes as determinants
      of salt tolerance in tomato, inducing enhanced Na(+) accumulation observed in the
      wild species when grown in the presence of NaCl.

PMID- 22153247
TI  - Selection of suitable inner reference genes for relative quantification
      expression of microRNA in wheat.
AB  - Quantitative real-time PCR (qRT-PCR) is currently the most accurate and widely
      applied method to detect differential genes expression, but choosing a suitable
      gene to be the internal control is a crucial factor for correct analysis of the
      results. MicroRNAs are fundamental regulatory genes of eukaryotic genomes, acting
      on several biological functions. Transcription accumulation of microRNAs has been
      studied using qRT-PCR, while no validated reference genes for microRNAs in wheat
      are available until now. In this study, nine previous reported housekeeping genes
      and ten wheat microRNAs were examined with regard to their use as normalizer and
      data was analyzed using geNorm and NormFind software. Expression stability of
      candidate inner reference genes was investigated in different conditions. After
      analysis of all the sample pools and samples after biotic and abiotic stress
      treatments, it was found that microRNAs had better expression stability than
      protein-coding genes, and mi167 and mi159 appeared to be the two most suitable
      reference genes in wheat. To confirm the stable expression of the putative
      reference genes in wheat, expression of mi171b of wheat was examined with inner
      reference genes mi167, mi159 and combination of mi157 and mi159 respectively. We
      provided evidence for that in order to get a more accurate result of gene
      expression, mi167 and mi159 should be used as inner reference gene for
      normalization together.

PMID- 22153248
TI  - Expressed sequence tag based identification and expression analysis of some cold
      inducible elements in seabuckthorn (Hippophae rhamnoides L.).
AB  - A cDNA library was constructed from the mature leaves of seabuckthorn (Hippophae
      rhamnoides). Expressed Sequence Tags (ESTs) were generated by single pass
      sequencing of 4500 cDNA clones. We submitted 3412 ESTs to dbEST of NCBI.
      Clustering of these ESTs yielded 1665 unigenes comprising of 345 contigs and 1320
      singletons. Out of 1665 unigenes, 1278 unigenes were annotated by similarity
      search while the remaining 387 unannotated unigenes were considered as organism
      specific. Gene Ontology (GO) analysis of the unigene dataset showed 691 unigenes
      related to biological processes, 727 to molecular functions and 588 to cellular
      component category. On the basis of similarity search and GO annotation, 43
      unigenes were found responsive to biotic and abiotic stresses. To validate this
      observation, 13 genes that are known to be associated with cold stress tolerance
      from previous studies in Arabidopsis and 3 novel transcripts were examined by
      Real time RT-PCR to understand the change in expression pattern under cold/freeze
      stress. In silico study of occurrence of microsatellites in these ESTs revealed
      the presence of 62 Simple Sequence Repeats (SSRs), some of which are being
      explored to assess genetic diversity among seabuckthorn collections. This is the
      first report of generation of transcriptome data providing information about
      genes involved in managing plant abiotic stress in seabuckthorn, a plant known
      for its enormous medicinal and ecological value.

PMID- 22153249
TI  - Selenium and spermine alleviate cadmium induced toxicity in the red seaweed
      Gracilaria dura by regulating antioxidants and DNA methylation.
AB  - The protective role of exogenously supplied selenium (Se) and polyamines (PAs)
      such as putrescine (Put) and spermine (Spm) in detoxifying the cadmium (Cd)
      induced toxicity was studied in the marine red alga Gracilaria dura in laboratory
      conditions. The Cd exposure (0.4 mM) impede the growth of alga while triggering
      the reactive oxygen species (ROS viz. O(2)(*-) and H(2)O(2)) generation,
      inhibition of antioxidant system, and enhancing the lipoxygenase (LOX) activity,
      malondialdehyde (MDA) level and demethylation of DNA. Additions of Se (50 MUM)
      and/or Spm (1 mM) to the culture medium in contrast to Put, efficiently
      ameliorated the Cd toxicity by decreasing the accumulation of ROS and MDA
      contents, while restoring or enhancing the level of enzymatic and nonenzymatic
      antioxidants and their redox ratio, phycobiliproteins and phytochelatins, over
      the controls. The isoforms of antioxidant enzymes namely superoxide dismutase (Mn
      SOD, ~150 kDa; Fe-SOD ~120 kDa), glutathione peroxidase (GSH-Px, ~120 and 140
      kDa), glutathione reductase (GR, ~110 kDa) regulated differentially to Se and/or
      Spm supplementation. Furthermore, it has also resulted in enhanced levels of
      endogenous PAs (specially free and bound insoluble Put and Spm) and n-6 PUFAs
      (C20-3, n-6 and C20-4, n-6). This is for the first time wherein Se and Spm were
      found to regulate the stabilization of DNA methylation by reducing the events of
      cytosine demethylation in a mechanism to alleviate the Cd stress in marine alga.
      The present findings reveal that both Se and Spm play a crucial role in
      controlling the Cd induced oxidative stress in G. dura.

PMID- 22153250
TI  - Pulsed magnetic field: a contemporary approach offers to enhance plant growth and
      yield of soybean.
AB  - The possible involvement of pulsed magnetic field (PMF) pretreatment in
      development and yield of soybean was investigated. Seeds were subjected to 20
      days with 1500 nT at 10.0 Hz of PMF for 5 h per day. PMF pretreatment increased
      the plant height, fresh and dry weight, and protein content with the changes of
      protein profile in 8 days old seedlings. In addition, activity of enzymes such as
      beta-amylase, acid phosphatase, polyphenol oxidase and catalase was enhanced
      while alpha-amylase, alkaline phosphatase, protease and nitrate reductase
      activities declined due to PMF exposure. However, a considerable increment of Fe,
      Cu, Mn, Zn, Mg, K and Na contents with reduced level of Ca was found in PMF
      treated seedlings. The number of leaves, pods, seeds and length of pods, and
      weight of seeds were also remarkably higher in PMF treatment in contrast to
      controls. The results suggest that pretreatment of PMF plays important roles in
      improvement of crop productivity of soybean through the enhancement of protein,
      mineral accumulation and enzyme activities which leads to increase the growth and
      yield.

PMID- 22153251
TI  - Differential expression of antioxidant enzymes and PR-proteins in compatible and
      incompatible interactions of cowpea (Vigna unguiculata) and the root-knot
      nematode Meloidogyne incognita.
AB  - This study aimed to evaluated the resistance and susceptibility of 10 cowpea
      cultivars to Meloidogyne incognita in field studies and to analyze the kinetics
      of the enzymes superoxide dismutase, catalase, peroxidase, chitinase, beta-1,3
      glucanases and cystein proteinase inhibitors in the root system of two
      contrasting cowpea cultivars after inoculation with M. incognita. The cultivars
      CE-31 and Frade Preto were highly resistant; CE-28, CE-01, CE-315, CE-237, were
      very resistant; CE-70 and CE-216 were moderately resistant, whereas Vita-3 and CE
      109 were slightly resistant. In the roots of the highly resistant cultivar CE-31
      the activity of the antioxidant enzyme superoxide dismutase increased and
      catalase decreased and those of the pathogenesis-related proteins chitinase, beta
      1,3-glucanase, peroxidase and cystein proteinase inhibitor increased in
      comparison with the root system of the slightly resistant CE-109, during the
      course of M. incognita infestation. Thus the changes in the activities of these
      enzymes might be related to the smaller final population of M. incognita in CE-31
      and may contribute to the high resistance of this cowpea cultivar against
      infection and colonization by this nematode species.

PMID- 22153252
TI  - Chemical composition of volatile oil from Artemisia ordosica and its allelopathic
      effects on desert soil microalgae, Palmellococcus miniatus.
AB  - Plants have been used to restore vegetation in desert region in Shapotou, where
      naturally biological soil crusts (BSCs) have formed after planting for several
      years. However, few works have been done on the allelopathic effects between the
      plants and soil microalgae in BSCs currently. In this study, we investigated the
      chemical compositions of volatile oil of Artemisia ordosica and its allelopathic
      effects on photosynthetic system II (PSII) and antioxidant system of
      Palmellococcus miniatus, a green algae isolated from BSCs. 37 components,
      consisted of 17 terpenoids, 14 alcohols, 2 esters, 2 ketones and other 2
      components were identified in the volatile oil from A. ordosica by GC-MS
      analysis. High concentration of volatile oil could significantly inhibit the
      growth and photosynthetic activity (Fv/Fm), and decreased the photosynthetic
      parameters by affecting photon absorption, electron transport and the reaction
      center of PSII of P. miniatus, and also cause the significant increase of
      superoxide dismutase (SOD; EC 1.15.1.) activity, peroxidase (POD; EC 1.11.1.7)
      activity, reactive oxygen evolution (ROS) and malondialdehyde (MDA) contents of
      P. miniatus through the combined effects of components in volatile oil. The
      results indicated that the emission of volatile oil of A. ordosica could inhibit
      the growth, photosynthesis of P. miniatus through the oxidative damage, and thus
      might negatively affect the development of BSCs.

PMID- 22153253
TI  - Responses of three different ecotypes of reed (Phragmites communis Trin.) to
      their natural habitats: leaf surface micro-morphology, anatomy, chloroplast
      ultrastructure and physio-chemical characteristics.
AB  - The adaptational characteristics due to long-term adaptation in the natural
      habitats of common reed (Phragmites communis Trin.) contrasted considerably among
      three different ecotypes: dune reed (DR), Gobi salt reed (GSR) and swamp reed
      (SR). The micromorphologies of leaf adaxial surfaces showed tapered setae and a
      non-smooth surface in DR, compound papillose structures with wax and hairs in
      GSR, but only papillose structures for the smooth surface of SR. Anatomical
      analysis showed that DR and GSR had higher bundle-sheath cell areas and a lower
      xylem/phloem ratio than SR. There were many sclerenchyma cells in vascular bundle
      of DR and GSR and crystal idioblasts in all ecotypes. Chloroplasts had ellipsoid
      shape in SR, but they were attached to the cell wall with oblong shape and
      contained many starch grains in DR and GSR. Higher concentrations of NO, H(2)O(2)
      and lipid peroxidation, higher ratio of carotenoids/chlorophyll and higher
      activities in T-AOC and SOD were found in DR and GSR. Na(+)/K(+)-ATPase and
      Ca(2+)/Mg(2+)-ATPase activities were greatest in GSR. All these data suggested
      that the greater relative stress tolerance of DR and GSR was due to a combination
      of morpho-anatomical adaptational characteristics and physio-chemical responses,
      and indicated the different mechanisms in their respective natural habitats.

PMID- 22153254
TI  - HrpZ harpins from different Pseudomonas syringae pathovars differ in molecular
      interactions and in induction of anion channel responses in Arabidopsis thaliana
      suspension cells.
AB  - HrpZ, a type three secretion system helper protein from the plant-pathogen
      Pseudomonas syringae, can be recognized by many plants as a defence elicitor.
      Responses of Arabidopsis thaliana suspension cells to different HrpZ variants
      were studied by electrophysiological methods and cell death assay. Purified HrpZ
      originating from a compatible pathogen P. syringae pv. tomato DC3000 (HrpZ(Pto))
      and incompatible P. syringae pv. phaseolicola (HrpZ(Pph)) both promoted
      Arabidopsis cell death. As an early response, both HrpZ variants induced an
      increase in time dependent K(+) outward rectifying current. In contrast, the
      effects of HrpZ proteins on anion currents were different: HrpZ(Pph) had no
      effect, and HrpZ(Pto) induced an anion current increase. This suggests that the
      observed responses of the K(+) channels and anion channels resulted from
      different and separable interactions and that the interaction implied in anion
      current modulation is host-specific. HrpZ(Pto) and HrpZ(Pph) also had a different
      sequence preference in phage display screen for peptide-binding. These peptides
      presumably represent a part of a putative target protein in the host, and HrpZ
      proteins of different P. syringae pathovars might have different binding
      specificities to match the allelic variation between plant species. Supporting
      the idea that the peptide-binding region of HrpZ is important for interactions
      with host cell components, we found that a mutation in that region changed the
      anion channel response of Arabidopsis cells.

PMID- 22153255
TI  - Acetic acid-induced programmed cell death and release of volatile organic
      compounds in Chlamydomonas reinhardtii.
AB  - Acetic acid widely spreads in atmosphere, aquatic ecosystems containing residues
      and anoxic soil. It can inhibit aquatic plant germination and growth, and even
      cause programmed cell death (PCD) of yeast. In the present study, biochemical and
      physiological responses of the model unicellular green algae Chlamydomonas
      reinhardtii were examined after acetic acid stress. H(2)O(2) burst was found in
      C. reinhardtii after acetic acid stress at pH 5.0 for 10 min. The photosynthetic
      pigments were degraded, gross photosynthesis and respiration were disappeared
      gradually, and DNA fragmentation was also detected. Those results indicated that
      C. reinhardtii cells underwent a PCD but not a necrotic, accidental cell death
      event. It was noticed that C. reinhardtii cells in PCD released abundant volatile
      organic compounds (VOCs) upon acetic acid stress. Therefore, we analyzed the VOCs
      and tested their effects on other normal cells. The treatment of C. reinhardtii
      cultures with VOCs reduced the cell density and increased antioxidant enzyme
      activity. Therefore, a function of VOCs as infochemicals involved in cell-to-cell
      communication at the conditions of applied stress is suggested.

PMID- 22153256
TI  - Reinitiation of anticoagulation after warfarin-associated intracranial hemorrhage
      and mortality risk: the Best Practice for Reinitiating Anticoagulation Therapy
      After Intracranial Bleeding (BRAIN) study.
AB  - BACKGROUND: While warfarin-related intracranial hemorrhage (ICH) occurs in 0.25%
      1.1% patients per year, little is known about the practice and outcomes of
      anticoagulant reinitiation. METHODS: We studied a cohort of consecutive patients
      with warfarin-related ICH (intracerebral or subarachnoid) admitted to 13 stroke
      centres in the Registry of the Canadian Stroke Network between July 2003 and
      March 2008. We examined patterns of warfarin reinitiation and variables
      associated with 30-day and 1-year outcomes. RESULTS: Among the 284 patients
      studied (mean age 74 +/- 12 years), warfarin was restarted in-hospital in 91
      patients (32%). Factors associated with restarting warfarin were lower stroke
      severity (adjusted odds ratio [aOR] 2.07, 95% confidence interval [CI]; 1.20
      3.57, P = 0.009) or presence of valve prosthesis (aOR 3.07, 95% CI; 1.29-7.27, P
      = 0.011). Mortality rates were not higher in those who restarted warfarin in
      hospital: 31.9% vs 54.4% (30-day, P < 0.001) and 48% vs 61% (1-year, P = 0.04),
      and bleeding was not increased. Multivariable predictors of mortality included
      initial international normalized ratio > 3.0 (aOR, 3.28 [30-day, P < 0.001] and
      3.32 [1-year, P = 0.003]), greater stroke severity (aOR, 6.04 [30-day] and 4.22
      [1-year]; both P < 0.001), and intraventricular hemorrhage (aOR, 2.19 [30-day; P
      = 0.03] and 2.04 [1-year; P = 0.04]). In selected patients who reinitiated
      warfarin, there was no increase in 30-day (aOR, 0.49; P = 0.03) or 1-year
      mortality (aOR, 0.79; P = 0.43). CONCLUSIONS: In selected patients at high
      thrombosis risk, reinitiation of warfarin after ICH did not confer increased
      mortality or bleeding events.

PMID- 22153257
TI  - WormKill to WormBoss--can we sell sustainable sheep worm control?
AB  - Despite the economic importance of nematodes for sheep enterprises, it is often
      difficult to convince producers to adopt best practice in worm control. In this
      paper we discuss key issues in effecting change by communicating worm control
      messages. The adoption of new strategies is affected by many factors including
      the relative advantage, complexity, compatibility and the ability to trial the
      proposed change. The visibility of the problem to be solved and proposed positive
      outcome are also important. Extension campaigns from the last 30 years, including
      "WormKill" and "CRACK", are used as examples, and future opportunities and tools,
      including the internet, for promoting best practice in sheep worm management are
      discussed.

PMID- 22153258
TI  - Detection of Toxoplasma gondii in free-range chickens in China based on
      circulating antigens and antibodies.
AB  - Toxoplasma gondii is widely distributed in humans and other animals including
      domestic poultry throughout the world, but the data on prevalence of T. gondii in
      free-ranged (FR) chickens in People's Republic of China (PRC) are limited. In the
      present study, the seroprevalence of T. gondii infection in FR chickens was
      investigated in 13 provinces/municipalities of China during the period from
      January to June 2010. A total of 1173 serum samples were collected and assayed
      for T. gondii circulating antigens (TCA) and antibodies (TCAb) using enzyme
      linked immunosorbent assay (ELISA) technique. Out of this number, 199 samples
      were TCA positive (16.97%), 226 samples were TCAb positive (19.27%), 69 samples
      were positive for both TCA and TCAb (5.88%), and the total seropositive rate was
      found in 356 of 1173 (30.36%). The results of the present survey indicated that
      infection with T. gondii in FR chickens is widely spread in China.

PMID- 22153259
TI  - Target-based and whole-worm screening approaches to anthelmintic discovery.
AB  - Experimental approaches for identifying new anthelmintics include target-based
      and whole-worm screening methods. The former involves basic research into
      characterising and validating new targets, mostly proteins, followed by
      identification of inhibitors or agonists through the use of target-based
      screening assays and/or in silico drug design. The latter experimental approach
      uses whole-worm assays to identify anthelmintic agents with unknown modes of
      action, or where the primary interest lies in whether analogues are able to kill
      (or disable) worms rather than in measuring their direct impact on their likely
      target. This paper focuses initially on the intestine and external layers of
      nematodes as potential drug targets. Specific anthelmintic agents targeting
      either tissue are discussed to illustrate the impact of disruption to these
      structures. In both cases, the activity of these agents against insects was
      known, and activity against nematodes was identified using whole worm screening
      assays. Recent literature identifying ecdysone signalling pathway receptors in
      nematodes is then used to provide an example of basic research into a specific
      target that may lead to the development of high-throughput target-based drug
      screening assays. Finally, the role of whole-worm screening approaches versus
      target-based screening is discussed briefly.

PMID- 22153260
TI  - The anti-protozoal activity of bronopol on the key life-stages of
      Ichthyophthirius multifiliis Fouquet, 1876 (Ciliophora).
AB  - PycezeTM (Novartis Animal Vaccines Ltd.) is licensed as a veterinary medicine to
      treat fungal infections in salmon, trout and their eggs. The active ingredient is
      bronopol, which due to its broad-spectrum activity has the potential to be an
      effective treatment against other important aquatic pathogens. In this study the
      efficacy of bronopol against Ichthyophthirius multifiliis was tested both in
      vitro and in vivo. In vitro trials demonstrated a 30 min exposure to 100 mg L(-1)
      bronopol killed 51.7% of the infective theronts. In vitro exposure of the
      protomonts to bronopol (0, 20, 50 and 100 mg L(-1)) for 30 min was observed to
      kill 0%, 76.2%, 97.2% and 100% respectively. Protomonts surviving treatment,
      demonstrated delayed development with the time taken from protomont until the
      release of theronts ranging from 28.3h for 0 mg L(-1) exposure, to 70 h for
      parasites in 20 and 50 mg L(-1) exposure groups. These concentrations also caused
      asymmetric cell division of the encysted tomonts. Exposure of encysted tomonts
      (min. 8 cell stage) to 100 mg L(-1) bronopol for 30 min, killed 50% within this
      period, with the remainder dying within the subsequent 42 h post exposure. Lower
      doses of bronopol were less effective in killing encysted tomonts than the higher
      doses (3.3% of parasites were killed in 20 mg L(-1); 10% in 50 mg L(-1)), but
      they still delayed theront release significantly (25.7 h for 0 mg L(-1) to 46.2h
      for parasites exposed to 20-50 mg L(-1)). Long, low dose (1 mg L(-1)) exposure to
      bronopol was also efficacious against theronts. Survival after 12h was 29% (c.f.
      100% in control parasites), and <1% after 24 h exposure (c.f. 74% in control
      parasites). Theronts surviving these exposures demonstrated reduced infection
      success compared to control theronts. The findings of this study demonstrate that
      bronopol (PycezeTM) affects the survival of all free-living stages of I.
      multifiliis (protomonts, tomont and theronts), thus suggesting that bronopol may
      serve a useful role in the control of I. multifiliis infections.

PMID- 22153261
TI  - Changes in hormonal profile, gonads and sperm quality of Argyrosomus regius
      (Pisces, Scianidae) during the first sexual differentiation and maturation.
AB  - In the present study, sexual gonadal differentiation and first sexual maturation
      of Meagre (Argyrosomus regius) was studied, based upon the annual changes in
      gonadosomatic index (GSI), gonadal histology, and the plasma steroid hormones,
      testosterone (T), 11-ketotestosterone (11-KT), and estradiol (E2). In addition,
      spermatozoa characteristics were evaluated by measuring sperm motility and
      morphology. Results demonstrated that Meagre completes sex differentiation at 10
      to 12 mo of age, and are group-synchronous spawners, which reach puberty at 2
      (mean length 26.8 +/- 0.7 cm, mean weight 920 +/- 75 g; N = 10) and 3 (mean
      length 35.8 +/- 0.8 cm, mean weight 1610 +/- 89 g; N = 10) years of age for males
      and females, respectively. In males, during the sex differentiation period, T
      levels were significantly higher with respect to those of 11-KT; this suggests
      that T has a key role in the early phases of the sex differentiation. During the
      spawning season an increase in plasma concentrations of all hormones was observed
      with 11-KT levels being significantly higher that those of T. In females, during
      the sex differentiation period, there was an increase in E2 plasma levels, while
      during the first spawning season, a significant increase of T and E2 levels were
      measured. Regarding sperm characteristics, the measured curvilinear velocity
      (VCL) and straight-linear velocity (VSL), resulted in the same order of magnitude
      with respect to those measured in other marine fish, while the average path
      velocity (VAP) was similar to that measured in the European Eel. The head of
      Meagre spermatozoa presents as oval shaped with a surface area of approximately
      3.66 MUm(2) and a perimeter of approximately 6.65 MUm. All these findings
      represent an important basis for further investigation on the reproductive
      biology of this specie and may assist the farmers to improve seed production in
      aquaculture.

PMID- 22153262
TI  - Study of the development of uteroplacental and fetal feline circulation by
      triplex Doppler.
AB  - The objective was to evaluate blood flow in fetal and maternal vessels by Triplex
      Doppler and its association with development of blood vessels during gestation in
      the domestic cat. Ten queens were examined weekly from 14 to 63 d after mating.
      Peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI)
      and pulsatility index (PI) of uteroplacental, aorta and umbilical fetal arteries
      and caudal vena cava of the fetus were evaluated. Throughout pregnancy, there was
      an increase in PSV and EDV in the aorta and umbilical arteries. In the caudal
      vena cava, there was an increase in PSV, whereas the EDV was constant, with a
      significant increase on Day 63. Peak systolic velocity and EDV of the
      uteroplacental artery reduced significantly on Day 63. Resistance index of the
      umbilical artery progressively decreased. In the aorta, this reduction was
      detected only on Day 42, with no defined pattern in the caudal vena cava and
      uteroplacental artery. Pulsatility index of the aorta varied. Although
      pulsatility increased in the caudal vena cava on Day 35 and remained elevated,
      pulsatility was significantly reduced in the umbilical artery by Day 63. The
      pulsatility index of the uteroplacental artery was constant (increased only on
      Day 63). Triplex Doppler evaluation could be a useful adjunct for prenatal care
      of pregnant queens, including assessment of vascular gestational development and
      prediction of gestational age.

PMID- 22153263
TI  - Effects of porcine granulocyte-macrophage colony-stimulating factor on porcine in
      vitro-fertilized embryos.
AB  - This study investigated the effects of porcine granulocyte-macrophage colony
      stimulating factor (pGM-CSF) on the developmental potential of porcine in vitro
      fertilized (IVF) embryos in chemically and semidefined (with BSA) medium. In
      experiment 1, zygotes were treated with different concentrations of pGM-CSF (0,
      2, 10, 100 ng/mL). The results indicated that 10 ng/mL pGM-CSF significantly (P <
      0.05) increased blastocyst development and total cell number (15.1% and 53.5,
      respectively) compared with the control (6.1%, and 38.8, respectively). Comparing
      blastocyst formation, early and expanded blastocyst formation was significantly
      higher in the 10 ng/mL-pGM-CSF group than in the control on Days 6 and 7 of the
      culture period. However, there was no significant difference in cleavage rate.
      Experiment 2 demonstrated that pGM-CSF influenced the percentage of blastocyst
      formation and total cell number when pGM-CSF was added during Days 4 to 7 (14.6%
      and 53.9, respectively) or Days 0 to 7 (15.2% and 54.0, respectively) compared
      with the control (7.8% and 43.1, respectively) and compared with Days 0 to 3
      (8.7% and 42.5, respectively). Similarly, early blastocyst formation rates were
      significantly higher at Days 4 to 7 than in the control, and expanded blastocyst
      formation was significantly higher at Days 4 to 7 or Days 0 to 7. No significant
      difference in cleavage rates appeared among the groups. In experiment 3, in the
      presence of BSA, pGM-CSF also increased the percentage of embryos that developed
      to the blastocyst stage and the total cell number (20.3% and 59.8, respectively)
      compared with the control (14.9% and 51.4, respectively), whereas there was no
      significant difference in cleavage rate. Experiment 4 found that the total cell
      number and the number of cells in the inner cell mass (ICM) were significantly
      increased compared with the control when zygotes were cultured in either porcine
      zygotic medium (PZM)-3 or PZM-4 supplemented with 10 ng/mL pGM-CSF. The number of
      trophectoderm (TE) cells was significantly higher in PZM-3 medium supplemented
      with pGM-CSF than in the control, and the number tended to increase (P = 0.058)
      in PZM-4 medium supplemented with pGM-CSF. The ratio of inner cell mass to
      trophectoderm cells was significantly higher in PZM-4 supplemented with 10 ng/mL
      pGM-CSF, but not in PZM-3. In experiment 5, it was found that the male pronuclear
      formation rate, monospermic penetration and sperm/oocyte were 95.4%, 37.2%, and
      2.4, respectively. Together, these results suggest that pGM-CSF may have a
      physiological role in promoting the development of porcine preimplantation
      embryos and regulating cell viability and that addition of pGM-CSF to IVC medium
      at Days 4 to 7 or 0 to 7 improves the developmental potential of porcine IVF
      embryos.

PMID- 22153264
TI  - The effect of chilling and cryoprotectants on hard coral (Echinopora spp.)
      oocytes during short-term low temperature preservation.
AB  - Understanding chilling sensitivity and chilling injury of coral oocytes, in the
      presence and absence of a cryoprotectant, is important in developing
      cryopreservation protocols, as well as for short-term storage and transport
      (e.g., for species conservation). The objective of this study was to investigate
      the chilling sensitivity of hard coral (Echinopora spp.) oocytes and the
      effectiveness of methanol (as a cryoprotectant) in protecting these oocytes
      during short-term, low temperature preservation. Oocytes were exposed to 0.5, 1,
      or 2 m methanol at 5, 0, or -5  degrees C for 1, 2, 4, 6, 8, 16, or 32 h, and
      their quality determined based on adenosine triphosphate (ATP) content. Methanol
      at 0.5 m was the most effective means to reduce chilling-induced reduction in ATP
      concentrations. Coral oocytes can be stored at room temperature for 4 h in
      filtered nature seawater with no detrimental effect on oocyte quality; however,
      in the present study, oocyte survival was extended for 8 h by addition of
      methanol in low concentrations (0.5 or 1 m) at low temperatures (5 and 0  degrees
      C). These findings should enhance conservation efforts and facilitate low
      temperature transport of endangered and threatened coral species.

PMID- 22153265
TI  - Stages and duration of the cycle of the seminiferous epithelium in oncilla
      (Leopardus tigrinus, Schreber, 1775).
AB  - Six adult Leopardus tigrinus (oncilla) were studied to characterize stages of the
      seminiferous epithelium cycle and its relative frequency and duration, as well as
      morphometric parameters of the testes. Testicular fragments were obtained
      (incisional biopsy), embedded (glycol methacrylate), and histologic sections
      examined with light microscopy. The cycle of the seminiferous epithelium was
      categorized into eight stages (based on the tubular morphology method). The
      duration of one seminiferous epithelium cycle was 9.19 d, and approximately 41.37
      d were required for development of sperm from spermatogonia. On average, diameter
      of the seminiferous tubules was 228.29 MUm, epithelium height was 78.86 MUm, and
      there were 16.99 m of testicular tubules per gram of testis. Body weight averaged
      2.589 kg, of which 0.06 and 0.04% were attributed to the testis and seminiferous
      tubules, respectively. In conclusion, there were eight distinct stages in the
      seminiferous epithelium, the length of the seminiferous epithelium cycle was
      close to that in domestic cats and cougars, and testicular and somatic indexes
      were similar to those of other carnivores of similar size.

PMID- 22153266
TI  - Temporal association of serum progesterone concentrations and vaginal cytology in
      walruses (Odobenus rosmarus).
AB  - Concentrations of serum estradiol-17beta and progesterone were monitored in six
      female walruses using an enzyme immunoassay. Progesterone concentrations
      increased from March to May in females aged 6 y or older, and subsequently
      declined (October). No significant elevation of estradiol-17beta concentration
      was detected before an elevation of progesterone concentration. Vaginal smears
      from four females were examined with Papanicolaou staining. In all females, most
      epithelial cells were basophilic intermediate-superficial cells; no color change
      from basophilic to eosinophilic of the cells was detected. Meanwhile, the
      percentage of anucleate cells in vaginal smears reached its highest value before
      the elevation of progesterone concentration, followed by an increase in the
      percentage of leukocytes. We inferred that the change in populations of anucleate
      cells and leukocytes in vaginal smears reflected ovarian status and CL formation
      in female walruses.

PMID- 22153267
TI  - Factors of a noninfectious nature affecting fertility after artificial
      insemination in lactating dairy cows. A review.
AB  - After 80 years of the commercial application of artificial insemination (AI) in
      the cow, the method still has numerous benefits over natural insemination
      including worldwide gene improvement. The efficiency of insemination depends,
      among many other factors, on the delivery of an appropriate number of normal
      spermatozoa to the appropriate reproductive tract site at the appropriate time of
      estrus. The metabolic clearance of steroid hormones and pregnancy associated
      glycoproteins and the negative effects of different types of stress related to
      high milk production makes the high-producing dairy cow a good animal model for
      addressing factors affecting fertility. Nevertheless, extensive studies have
      shown a positive link between high milk production in an individual cow and high
      fertility. When a cow becomes pregnant, the effect of pregnancy loss on its
      reproductive cycle is also a topic of interest. This paper reviews the factors of
      a noninfectious nature that affect the fertility of lactating dairy cows
      following AI. Special attention is paid to factors related to the cow and its
      environment and to estrus confirmation at insemination. Pregnancy maintenance
      during the late embryonic/early fetal period is discussed as a critical step.
      Finally, the use of Doppler ultrasonography is described as an available research
      tool for improving our current understanding of the health of the genital
      structures and conceptus.

PMID- 22153268
TI  - Impact of genomic selection of AI dairy sires on their likely utilization and
      methods to estimate fertility: a paradigm shift.
AB  - Breeding of dairy cattle is undergoing a paradigm shift to genomic selection of
      potential sires and dams. This undoubtedly will affect how bulls are managed in
      an artificial insemination (AI) center and impact methods to estimate their
      'fertility'. Our goal is to help decision-makers understand the contents of a
      straw of semen, current estimates of sire fertility, and how estimates might
      evolve in a genomic era. Sire fertility is estimated from outcome (pregnant or
      not) after 300 to > 2,000 inseminations and reported in units (U) as a sire's
      deviation from a population (> 500 bulls) average pregnancy rate (PR). Too often
      users do not recognize that imprecision of an estimate encompasses a 3-U range,
      or more. 'True fertility' of the sire whose semen is inseminated influences
      outcome far less than 'true fertility' of each female and a myriad of
      microenvironment and management factors. Further, AI centers discard substandard
      collections and intentionally adjust number of sperm per straw so that
      differences in pregnancy rates achieved by different sires are minimized! For >
      80% of Holstein bulls, estimated 'sire conception rates' are within a 5.4-U
      range. In the future, most sires will be 15 to 40 mo old and services will
      accumulate at > 1,000/mo. Estimated sire conception rates still will be a
      deviation from the population mean, but should be based on records for the most
      recent 6 or 12 mo, rather than 48 or 60 mo. Repeated 'snap shots' every 2 mo
      would allow AI centers to adjust number of sperm per AI straw from genomic-sires
      in a timely manner, to maintain high pregnancy rates, and to meet market demands
      with sires producing ~40% as many sperm as mature 'proven sires' of yesteryear.

PMID- 22153269
TI  - Abaxial tail implantation in the emu, Dromaius novaehollandiae: morphological
      characteristics and origin of a rare avian sperm defect.
AB  - Abaxial tail implantation is a defect occurring in the neck region of spermatozoa
      and is characterized by misalignment of the centriolar complex relative to the
      head base. This defect has been described in a number of mammalian species, but
      is rarely reported in birds. In this study, a detailed description of the defect
      in emu sperm is presented as well as morphological evidence of its origin in the
      testis. Despite their low incidence defective sperm could readily be identified
      using light (LM) and transmission electron microscopy (TEM). Affected sperm
      displayed obvious misalignment of the head and flagellum with many cells
      additionally showing unilateral swelling and caudal extension of the nuclear
      base. This material overlapped the anterior aspect of the centriolar complex.
      More subtle forms of the defect which were not resolved by LM were revealed by
      TEM. Abaxial sperm development could be identified in the testis during the early
      elongated spermatid stage of spermiogenesis. At this stage the centriolar complex
      was clearly misaligned with respect to the longitudinal axis of the condensing
      and elongating nucleus. The rare occurrence and low incidence of this defect in
      the emu would suggest that it has little effect on fertility.

PMID- 22153270
TI  - How type of parturition and health status influence hormonal and metabolic
      profiles in newborn foals.
AB  - Thyroid hormones, insulin growth factor I (IGF-I) and non-esterified fatty acids
      (NEFA) represent important hormonal and metabolic factors associated with
      perinatal growth and maturation. Their action could be influenced by the type of
      parturition and the health status of the foal and therefore the aim of this work
      is to evaluate their plasma concentrations in newborn foals during the first 2
      wks of life. Three groups of subjects were enrolled: 15 healthy foals born by
      spontaneous parturition, 24 healthy foals born by induced parturition and 26
      pathologic foals. From each of the healthy foals, blood was collected at 10, 20
      and 30 minutes, 3 and 12 hours from birth, daily from Day 1 to Day 7, and at Day
      10 and 14 of life. In pathologic foals samples were collected twice a day from
      the day of admission at the hospital until the day of discharge or death. Thyroid
      hormones (T3 and T4) and IGF-I were analyzed by radioimmunoassay and NEFA by
      enzymatic-colorimetric methods. In all the three groups a declining trend of T3
      and T4 plasma concentrations was detectable, with lower levels in the pathologic
      group compared to healthy foals. Spontaneous foals showed higher levels of T3 at
      7 d compared to induced foals, while T4 levels were higher in spontaneous vs.
      induced foals before 6 h of life, at three and seven days. IGF-I showed
      increasing plasma concentrations in all three considered groups. No differences
      were found between healthy and pathologic foals. NEFA in spontaneous and induced
      healthy foals showed a declining trend with higher levels during the first hours
      of life. Pathologic foals presented higher levels compared to spontaneous foals
      only at 24 h and 10 d. These data suggest that the type of foaling could
      influence the reference ranges for thyroid hormones. Moreover, pathologic foals
      showed some hormonal and metabolic differences related to their health status.
      Above all changes of thyroid hormones levels, early in postnatal life, could be a
      cause, and not only a consequence, of the diseased condition of these foals.

PMID- 22153271
TI  - The reproductive performance of Thoroughbred mares treated with intravaginal
      progesterone at the start of the breeding season.
AB  - The objective of this study was to investigate the effects of intravaginal
      progesterone on the reproductive performance of transitional Thoroughbred mares
      on commercial stud farms. Two hundred twenty-seven (227) non-lactating
      transitional Thoroughbred mares aged between 4 and 18 y (mean 9.4 +/- 3.2 y)
      located on three stud farms in the Waikato region of New Zealand were used in the
      study performed during four consecutive breeding seasons (2007-10). Mares were
      age-matched in pairs and either treated with an intravaginal progesterone
      releasing device (Cue-Mare, 1.72 g progesterone, 10% w/w) for up to 10 d
      (Treated; n = 126) or left untreated (Control; n = 101). In both groups, 1,667 iu
      of hCG was given IV when an ovarian follicle >=35 mm was detected (in conjunction
      with estrous behavior) and each mare was bred by natural service. Treated mares
      were served earlier in the breeding season (mean +/- SD interval to first service
      was 13.9 +/- 3.0 vs 26.7 +/- 13.2 d for Treated and Control groups, respectively;
      P < 0.001). In the Treated and Control groups, 95.2 and 42.6% of mares were
      served within the first 21 d of the season (P < 0.001). Treated mares conceived
      earlier in the breeding season (mean number of days to conception 37.5 +/- 14.2
      vs 50.8 +/- 21.3 d, P = 0.01). There was no difference between groups in the
      first service pregnancy rates (53.9 and 50.5% for Treated and Control mares, P =
      0.89). Treatment with an intravaginal device increased the number of mares
      conceiving by the end of the breeding season (91.3 vs 82.3% for Treated and
      Control groups, P = 0.04). Therefore, this treatment protocol appeared to offer a
      convenient, economical and reliable method for managing transitional mares on
      commercial Thoroughbred stud farms.

PMID- 22153272
TI  - Incorporation of ascorbic acid and alpha-tocopherol to the extender media to
      enhance antioxidant system of cryopreserved sea bass sperm.
AB  - Despite the overwhelming application of sperm cryopreservation in aquaculture and
      broodstock management, its detrimental effects on sperm quality must be taken
      into account. Imbalance of reactive oxygen species is considered one of the main
      triggers of cell damage after cryopreservation, because the spermatozoa
      antioxidant system is decimated during this process, mainly because the natural
      antioxidants present in seminal plasma diminish when sperm is diluted in
      extenders. It has been demonstrated that the addition of antioxidants to the
      extender improves the quality of thawed sperm. Thus, the aim of the present work
      was to evaluate the status of the antioxidant system in cryopreserved sea bass
      sperm, and the possibility of enhancing this system to reduce oxidation of the
      membrane compounds by extender supplementation with vitamins. To do this, sperm
      from European sea bass (Dicentrarchus labrax) was cryopreserved using an extender
      control (NAM), supplemented with 0.1 mm alpha-tocopherol or 0.1 mm ascorbic acid.
      Sperm motility (computer assisted sperm analysis (CASA) parameters), viability
      (SYBR Green/propidium iodide (PI)), lipid peroxidation (malondialdehyde (MDA)
      levels) and protein oxidation (DNPH levels) were analyzed, as well as the status
      of the sperm antioxidant system by determining glutathione peroxidase,
      glutathione reductase and superoxide dismutase (GPX, GSR and SOD) activity. The
      results demonstrated that extenders containing vitamins significantly increased
      sperm motility. Total motility, velocity and linearity increased from 31.2 +/-
      3.0 MUm/sec, 18.3 +/- 1.7 MUm/sec and 46.9 +/- 2.0% in extender containing 0.1 mm
      alpha-tocopherol or 30.6 +/- 3.9 MUm/sec, 19.5 +/- 1.6 MUm/sec and 47.9 +/- 2.2%
      in extender containing 1 mm ascorbic acid respect to the extender control (20.7
      +/- 3.3 MUm/sec, 13.8 +/- 1.7 MUm/sec and 37.3 +/- 4.1%). However, viability and
      levels of lipid peroxidation and protein oxidation were not affected by the
      presence of these antioxidants, suggesting that membrane impairment could be more
      associated to osmotic shock or membrane destabilization than oxidative damage.
      The increased activity of both GPX and GSR after cryopreservation showed that the
      antioxidant system of sea bass sperm must play an important role in preventing
      oxidation of the membrane compounds. In conclusion, the addition of alpha
      tocopherol and ascorbic acid to the extender media, together with the antioxidant
      system of the spermatozoa improved sea bass sperm motility, which is one of the
      impairment parameters most affected by cryopreservation.

PMID- 22153273
TI  - Vitrification of non-human primate immature testicular tissue allows maintenance
      of proliferating spermatogonial cells after xenografting to recipient mice.
AB  - This study demonstrates preservation of tissue integrity, maintenance of
      proliferating spermatogonia and Leydig cell functionality after vitrification and
      transplantation of non-human primate immature testicular tissue. The objective
      was to assess the potential of vitrification of non-human primate immature
      testicular tissue (ITT) in an in vivo xenotransplantation model. Testicular
      tissue was obtained from one immature rhesus monkey (Macaca mulatta) aged 4
      years. Collection and vitrification of testicular tissue, followed by short-term
      xenografting (3 wks) to nude mice were performed to evaluate and compare
      vitrified/warmed and fresh tissue. Fresh ungrafted tissue was used for control
      purposes. Cell density and seminiferous tubule (ST) integrity were assessed by
      light microscopy. Presence of spermatogonia (SG) (MAGE-A4), proliferation (Ki-67)
      and Leydig cell (LC) functionality (3beta-hydroxysteroid dehydrogenase; 3beta
      HSD) were evaluated by immunohistochemistry (IHC). Qualitative analysis revealed
      preservation of the histologic characteristics of SG and Sertoli cells (SCs), as
      well as cell-cell cohesion and cell adhesion to the basement membrane, in both
      vitrified and fresh grafted tissues. Survival of SG able to proliferate and
      functional LCs was confirmed by IHC in fresh and vitrified grafts. In conclusion,
      vitrification appears to be a promising approach, representing an alternative
      strategy to slow-freezing in the emerging field of ITT cryopreservation and
      cryobanking.

PMID- 22153274
TI  - Effects of gonadotropin-releasing hormone administration on the pituitary-gonadal
      axis in male and female dogs before and after gonadectomy.
AB  - GnRH-stimulation tests were performed in 14 female and 14 male client-owned dogs
      of several breeds, before and 4 to 5 mo after gonadectomy. The aim of the study
      was to obtain more insight into the pituitary-gonadal axis in intact and neutered
      dogs and to establish reference values. Basal plasma luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH) concentrations were increased significantly
      after gonadectomy in both bitches and male dogs. In both males and females ranges
      of the basal plasma FSH concentrations, before and after gonadectomy, did not
      overlap as opposed to the overlap in ranges of the basal plasma LH
      concentrations. Before gonadectomy basal plasma LH concentrations were lower and
      basal plasma FSH concentrations were higher in bitches than in male dogs. After
      gonadectomy these basal values did not differ significantly. GnRH administration
      before gonadectomy resulted in an increase in plasma LH and FSH concentrations in
      both genders. GnRH administration after gonadectomy produced an increase only in
      plasma LH concentrations in both genders, and a just significant increase in
      plasma FSH in castrated male dogs. GnRH administration before gonadectomy
      resulted in a significant increase in plasma testosterone concentration in both
      genders. In males ranges of basal and GnRH-stimulated plasma testosterone
      concentrations before and after gonadectomy did not overlap. Basal plasma
      estradiol concentrations were significantly higher in intact males than in
      castrated males and their ranges did not overlap. The basal estradiol
      concentrations in bitches before and after ovariectomy were not significantly
      different. At 120 min after GnRH administration, ranges of plasma estradiol
      concentration of intact and ovariectomized bitches no longer overlapped. In
      conclusion, basal plasma FSH concentration appears to be more reliable than basal
      plasma LH concentration for verification of neuter status in both male and female
      dogs. The basal plasma testosterone concentration appears to be reliable for
      verification of neuter status in male dogs. The plasma estradiol concentration at
      120 min after GnRH administration can be used to discriminate between bitches
      with and without functional ovarian tissue.

PMID- 22153275
TI  - Coculturing denuded oocytes during the in vitro maturation of bovine cumulus
      oocyte complexes exerts a synergistic effect on embryo development.
AB  - The present study examined the effect of coculturing cumulus oocyte complexes
      (COCs) and denuded oocytes (DOs) during in vitro maturation (IVM) on nuclear and
      cytoplasmic maturation, zona pellucida (ZP) hardening, the pattern of
      fertilization and glutathione peroxidase 1 (GPX1) gene expression in the oocyte.
      Furthermore, the rate of embryonic development and the quality of blastocysts
      were examined for both COCs and DOs. Three IVM conditions were studied: 1) the
      coculture of 12 COCs and 60 DOs, 2) COC control with 12 COCs, and 3) DO control
      with 60 DOs. The IVM was performed in a 120-MUl droplet of TCM199-based IVM
      medium. Following IVM, in vitro fertilization (IVF) and in vitro culture (IVC)
      were conducted separately for the COCs and DOs (DO coculture) from the IVM
      coculture group. Coculturing COCs and DOs increased the percentage of oocytes
      reaching the blastocyst stage and the total number of cells per blastocyst in
      both the COC coculture (44.4 +/- 8.6 vs 26.7 +/- 9.7%, P < 0.01, and 137.9 +/-
      24.9 vs 121.7 +/- 21.1, P < 0.05) and the DO coculture (20.5 +/- 5.0 vs 11.1 +/-
      2.5%, P < 0.01, and 121.9 +/- 27.5 vs 112.3 +/- 33.2, P < 0.05) compared to their
      respective control groups. The synergistic effects of coculturing were detected
      as increased nuclear and cytoplasmic maturation, the prevention of ZP hardening,
      increased monospermic fertilization and increased expression of GPX1 in the
      oocytes in response to endogenous oocyte-secreted factors. In conclusion,
      coculturing COCs and DOs may be an effective culture system for both intact COCs
      and immature DOs.

PMID- 22153276
TI  - Lanthanide doping-facilitated growth of ultrasmall monodisperse Ba2LaF7
      nanocrystals with excellent photoluminescence.
AB  - Lanthanide doping not only works as sensitizer and activator, but also plays an
      important role to facilitate the growth of nanocrystal and to control the size,
      shape, and property of nanocrystals. Here, reported was the synthesis of
      monodisperse Ba(2)LaF(7) nanocrystals with the size of sub-10nm through a
      solvothermal method. We found the dopants of Ho(3+), Er(3+), or Yb(3+)
      facilitated the growth of Ba(2)LaF(7) nanocrystals obviously to a certain size
      within a shorter reaction time. Similar phenomenon can also be observed in the
      synthesis of LaF(3) nanocrystals. We find that Ln(3+) (e.g., Ho(3+), Er(3+), or
      Yb(3+)) with smaller radius can reduce the nucleation energy and lead to
      heterogeneous nucleation, which favors the growth of Ba(2)LaF(7) nanocrystals
      obviously. In addition, intense upconversion emission can be observed from Ln(3+)
      doped Ba(2)LaF(7) nanocrystals under the 980 nm laser excitation, providing great
      potential application in biological imaging. Especially, Ba(2)LaF(7):Yb/Er (20/1
      mol%) nanocrystals present more intense upconversion emission than alpha
      NaYF(4):Yb/Er (20/1 mol%) nanocrystals under the same conditions.

PMID- 22153277
TI  - The influence of nanoparticle architecture on latex film formation and healing
      properties.
AB  - We present a study of chain interdiffusion in films formed by specially
      architectured PBMA nanoparticles by Forster Resonance Energy Transfer -FRET.
      Polymer nanoparticles contained linear chains with narrower molecular weight
      distributions than other previous reports, allowing a more detailed study.
      Apparent fractions of mixing and diffusion coefficients, determined from the
      quantum efficiency of energy transfer, were used to characterize the
      interdiffusion mechanism in the different films. The resistance of the films to
      dissolution by a good solvent was finally correlated with the interdiffusion
      results, in order to get information about film healing. We concluded that
      whenever interdiffusion occurs between nanoparticles containing linear chains and
      fully cross-linked nanoparticles, healing becomes more effective in spite of
      showing slower interdiffusion. We also observed that particles with longer chains
      are more effective for film healing. Finally, we concluded that interdiffusion
      occurs both ways across interfaces in blends formed by particles swollen with
      linear chains of different molecular weights.

PMID- 22153278
TI  - Surface characterization and liquid crystal alignment behavior of comb-like
      poly(oxyethylene)/poly(3-hexylthiophene) blend films.
AB  - The blend surfaces of poly[oxy(n-decylsulfonylmethyl)ethylene] (CH(3)-10SE) and
      poly (3-hexylthiophene) (P3HT) with different weight ratios were prepared by spin
      coating the polymer solution mixtures. In this study, their surface properties
      such as surface morphology, chemical composition, molecular structure, and
      wettability were systematically studied and correlated with liquid crystal (LC)
      alignment behaviors on the blend films. Therefore, we found that CH(3)-10SE part
      with a well-ordered side chain structure predominantly affects the both of
      wettability and LC alignment behavior of the blend films while there was no clear
      association between the wettability and the LC alignment behavior.

PMID- 22153279
TI  - Maternal sepsis during pregnancy or the postpartum period requiring intensive
      care admission.
AB  - BACKGROUND: Previous studies on severe maternal sepsis during pregnancy or the
      postpartum period are rare and have focused on septic abortion. Voluntary
      abortion was legalized in France in 1975. This study was conducted to reassess
      the characteristics of maternal sepsis that have been managed in a French
      intensive care unit. METHODS: A retrospective study of 66 women admitted to an
      intensive care unit for sepsis from 1977-2008 was performed. Data on sources of
      infection, microbial agents and maternal and fetal outcomes were collected. Data
      from 1977-1992 and 1993-2008 were compared. RESULTS: Over time, the rate of
      intensive care admission for maternal sepsis did not change (0.75 episodes per
      1000 deliveries in 1977-1992 versus 0.72/1000 in 1993-2008, P=1.0). The
      percentage of septic abortions decreased from 14% to 0%, whereas that of
      antepartum infections increased from 50% to 79% (P<0.01). The percentage of non
      bacterial infections increased from 0% to 19% (P=0.04), and the percentage of
      pelvic infections had a tendency to decrease from 54% to 27% (P=0.06). Pelvic
      infections were due to enterobacteriaceae (50%), gram-positive cocci (45%),
      and/or anaerobes (23%). Maternal and fetal mortality rates were 6% and 33%,
      respectively. CONCLUSIONS: Over time, our intensive care unit has seen fewer
      cases of septic abortion. However, maternal sepsis remained a cause of intensive
      care admission and both maternal and fetal death. The percentages of antepartum
      and non-bacterial infections have increased over time. A prospective multicentre
      study is required to confirm these results and to investigate questions such as
      the effect of maternal sepsis on long-term fetal outcome.

PMID- 22153280
TI  - A prospective controlled study of continuous spinal analgesia versus repeat
      epidural analgesia after accidental dural puncture in labour.
AB  - BACKGROUND: After accidental dural puncture in labour it is suggested that
      inserting an intrathecal catheter and converting to spinal analgesia reduces
      postdural puncture headache and epidural blood patch rates. This treatment has
      never been tested in a controlled manner. METHODS: Thirty-four hospitals were
      randomised to one of two protocols for managing accidental dural puncture during
      attempted labour epidural analgesia: repeating the epidural procedure or
      converting to spinal analgesia by inserting the epidural catheter intrathecally.
      Hospitals changed protocols at six-month intervals for two years. RESULTS: One
      hundred and fifteen women were recruited but 18 were excluded from initial
      analysis because of practical complications which had the potential to affect the
      incidence of headache and blood patch rates. Of the remaining 97 women, 47 were
      assigned to the repeat epidural group and 50 to the spinal analgesia group.
      Conversion to spinal analgesia did not reduce the incidence of postdural puncture
      headache (spinal 72% vs. epidural 62%, P=0.2) or blood patch (spinal 50% vs.
      epidural 55%, P=0.6). Binary logistic analysis revealed the relative risk of
      headache increased with 16-gauge vs. 18-gauge epidural needles (RR=2.21, 95% CI
      1.4-2.6, P=0.005); anaesthetist inexperience (RR=1.02 per year difference in
      experience, 95% CI 1.001-1.05, P=0.043), and spontaneous vaginal compared to
      caesarean delivery (RR=1.58, 95% CI 1.14-1.79, P=0.02). These same factors also
      increased the risk of a blood patch: 16-gauge vs. 18-gauge needles (RR=2.92, 95%
      CI 1.37-3.87, P=0.01), anaesthetist inexperience (RR=1.06 per year difference in
      experience, 95% CI 1.02-1.09, P=0.006), spontaneous vaginal versus caesarean
      delivery (RR=2.22, 95% CI 1.47-2.63, P=0.002). When all patients were included
      for analysis of complications, there was a significantly greater requirement for
      two or more additional attempts to establish neuraxial analgesia associated with
      repeating the epidural (41% vs. 12%, P=0.0004) and a 9% risk of second dural
      puncture. CONCLUSIONS: Converting to spinal analgesia after accidental dural
      puncture did not reduce the incidence of headache or blood patch, but was
      associated with easier establishment of neuraxial analgesia for labour. The most
      significant factor increasing headache and blood patch rates was the use of a 16
      gauge compared to an 18-gauge epidural needle.

PMID- 22153281
TI  - mtSSB may sequester UNG1 at mitochondrial ssDNA and delay uracil processing until
      the dsDNA conformation is restored.
AB  - Single-strand DNA binding proteins protect DNA from nucleolytic damage, prevent
      formation of secondary structures and prevent premature reannealing of DNA in DNA
      metabolic transactions. In eukaryotes, the nuclear single-strand DNA binding
      protein RPA is essential for chromosomal DNA replication and transcription and
      directly participates in several DNA repair processes by binding to and
      modulating the activity of repair factors. Much less is known about the
      involvement of the only mitochondrial single-strand binding protein mtSSB in the
      context of DNA repair. Here we demonstrate that mtSSB impedes excision of uracil
      and oxidative demethylation of 3meC in single-stranded DNA by UNG1 and ABH1,
      respectively, whereas excision by NEIL1 was partially inhibited. mtSSB also
      effectively inhibited nicking of single-stranded DNA by APE1 and ABH1 and
      partially inhibited the lyase activity of NEIL1. Finally we identified a putative
      surface motif in mtSSB that may recruit UNG1 to DNA-bound mtSSB. We suggest that
      the massive amount of mtSSB in mitochondria effectively prevents processing of
      uracil and other types of damaged bases to avoid introduction of nicks in single
      stranded mtDNA formed during replication. Local enrichment of UNG1 at DNA-bound
      mtSSB may furthermore facilitate rapid access to- and processing of the damage
      once the dsDNA conformation is restored. This could be of potential biological
      importance, since mitochondria have no or limited capacity for homologous
      recombination to process nicks at the replication fork.

PMID- 22153282
TI  - New trends in fast liquid chromatography for food and environmental analysis.
AB  - There is an increasing need for applications in food and environmental areas able
      to cope with a large number of analytes in very complex matrices. The new
      analytical procedures demand sensitivity, robustness and high resolution within
      an acceptable analysis time. The purpose of this review is to describe new trends
      based on fast liquid chromatography applied to the food and environmental
      analysis. It includes different column technologies, such as monolithic, sub-2
      MUm, porous shell, as well as different stationary phases such as reversed phase
      (C8 and C18), hydrophilic interaction liquid chromatography (HILIC) and
      fluorinated columns. Additionally, recent sample extraction and clean-up
      methodologies applied to reduce sample manipulation and total analysis time in
      food and environmental analysis--QuEChERS (Quick, Easy, Cheap, Effective, Rugged
      and Safe), on line solid phase extraction coupled to ultrahigh pressure liquid
      chromatography (on line SPE-UHPLC), turbulent flow chromatography (TFC) and
      molecularly imprinted polymers (MIPs), were also addressed. The advantages and
      drawbacks of these methodologies applied to the fast and sensitive analyses of
      food and environmental samples are going to be discussed.

PMID- 22153283
TI  - Determination of nicotine and N-nitrosamines in house dust by pressurized liquid
      extraction and comprehensive gas chromatography--nitrogen chemiluminiscence
      detection.
AB  - A novel, highly selective method for the determination of nicotine, N
      nitrosamines and tobacco-specific nitrosamines (TSNAs) in indoor dust samples is
      presented in this study. Samples were extracted by in-cell clean-up pressurized
      liquid extraction (PLE) that allows high extraction efficiency with moderate
      consumption of organic solvents. The extracts were analyzed by comprehensive gas
      chromatography and detected with a nitrogen chemiluminiscence detector (GC*GC
      NCD) that provided enhanced selectivity and sensitivity for organic nitrogen
      containing compounds. Method validation showed good linearity, repeatability and
      reproducibility (%RSD<8%). Recovery was higher than 80% for most target compounds
      and limits of detection lower than 16 ng g(-1). The method was used for the
      determination of the nitrosamine target compounds in house dust samples from both
      smoking and non-smoking households. All the analytes were found in the samples,
      nicotine being the most abundant compound in smokers' dust and one of the most
      abundant in non-smokers' dust. To our knowledge this is the first time that
      volatile N-nitrosamines and TSNAs have been determined in indoor dust samples.
      The results demonstrate the presence of these highly carcinogenic compounds in
      house dust, with inherent human exposure through inhalation and/or involuntary
      ingestion of house dust.

PMID- 22153284
TI  - Performance limits and kinetic optimization of parallel and serially connected
      multi-column systems spanning a wide range of efficiencies for liquid
      chromatography.
AB  - Using a set of experimentally determined liquid chromatography column performance
      data, it has been investigated how a range of efficiencies can best be covered
      when using a multi-column system. Two main variants are considered: a serially
      connected variant (realizing different column lengths by connecting a different
      number of column segments in series) and a parallel-connected variant (realizing
      different column lengths by simply switching between columns with a different
      length arranged in parallel). Both variants are compared for their ability to
      keep the average analysis time along a given range of efficiencies as close as
      possible to the intrinsic Knox & Saleem-speed limit. It was found that the serial
      connection mode offers a better compromise between average speed and amount of
      required silica (total required column length) than the parallel connection mode
      for all efficiency ranges running from 5000-10,000 plates up to 75,000-150,000
      plates. Considering an ultra-high performance liquid chromatography (UHPLC)
      operation at 1200 bar, the best possible serial connection system can get within
      about within 15-25% of the Knox & Saleem-speed limit, whereas a three-column
      parallel system can only get to within 40-50% of the speed limit, while needing
      50-100% more total column length. In absolute terms, the serially-connected
      system with individually optimized segment lengths should be able to cover a
      range of 5000-75,000 theoretical plates (dynamic range of 25) in an average
      analysis time of 14.3 min when using a 1200 bar instrument. At 400 bar, this
      would be 37.9 min, showing that the construction of wide-efficiency range systems
      would be one of the application areas where the advantages of UHPLC-conditions
      would be most fully realized.

PMID- 22153285
TI  - Chromatographic approaches for determination of low-molecular mass aldehydes in
      bio-oil.
AB  - HPLC-UV and GC/MS determination of aldehydes in bio-oil were evaluated. HPLC-UV
      preceded by derivatization with 2,4-dinitrophenylhydrazine allows separation and
      detection of bio-oil aldehydes, but the derivatization affected the bio-oil
      stability reducing their quantitative applicability. GC/MS determination of
      aldehydes was reached by derivatization with o-(2,3,4,5,6-pentafluorobenzyl)
      hydroxylamine hydrochloride. Two approaches for this reaction were evaluated. The
      first: "in solution derivatization and head space extraction" and the second: "on
      fiber derivatization SPME", the latter through an automatic procedure. Both
      sample treatments allows the quantification of most important aliphatic aldehydes
      in bio-oil, being the SPME approach more efficient. The aldehyde concentrations
      in bio-oil were ~2% formaldehyde, ~!0.1% acetaldehyde and ~0.05% propionaldehyde.

PMID- 22153286
TI  - Ultra-preconcentration and determination of thirteen organophosphorus pesticides
      in water samples using solid-phase extraction followed by dispersive liquid
      liquid microextraction and gas chromatography with flame photometric detection.
AB  - An ultra-preconcentration technique composed of solid-phase extraction (SPE) and
      dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography
      flame photometric detection (GC-FPD) was used for determination of thirteen
      organophosphorus pesticides (OPPs) including phorate, diazinon, disolfotane,
      methyl parathion, sumithion, chlorpyrifos, malathion, fenthion, profenphose,
      ethion, phosalone, azinphose-methyl and co-ral in aqueous samples. The analytes
      were collected from large volumes of aqueous solutions (100 mL) into 100 mg of a
      SPE C(18) sorbent. The effective variables of SPE including type and volume of
      elution solvent, volume and flow rate of sample solution, and salt concentration
      were investigated and optimized. Acetone was selected as eluent in SPE and
      disperser solvent in DLLME and chlorobenzene was used as extraction solvent.
      Under the optimal conditions, the enrichment factors were between 15,160 and
      21,000 and extraction recoveries were 75.8-105.0%. The linear range was 1-10,000
      ng L(-1) and limits of detection (LODs) were between 0.2 and 1.5 ng L(-1). The
      relative standard deviations (RSDs) for 50 ng L(-1) of OPPs in water with and
      without an internal standard, were in the range of 1.4-7.9% (n=5) and 4.0-11.6%,
      respectively. The relative recoveries of OPPs from well and farm water sat
      spiking levels of 25 and 250 ng L(-1) were 88-109%.

PMID- 22153287
TI  - Cigarette smoke exacerbates ventricular remodeling and dysfunction in the volume
      overloaded heart.
AB  - Cigarette smoking is an independent risk factor for heart disease and is linked
      to sudden cardiac death. In this study, we examined the effects of cigarette
      smoke (CS) on the volume overload stressed heart. Our hypothesis was that CS
      exacerbates volume overload (VO)-induced cardiac dysfunction by accelerating
      ventricular remodeling. VO stress was surgically induced in male Sprague-Dawley
      rats by abdominal aortocaval fistula (ACF). Rats, with and without ACF, were
      exposed to either room air or CS (6 cigarettes/day) for 6 weeks. Temporal
      echocardiogram measurements indicated that CS significantly increased VO-induced
      left ventricular dilatation, prevented compensatory wall thickening, and
      depressed fractional shortening. Morphological analysis of ventricular collagen
      revealed that CS blunted compensatory collagen expression (45% decrease versus
      ACF alone). CS exacerbated the VO-induced increase of MMP-9 and TIMP-1 expression
      in the heart. CS also blocked the compensatory increases of HIF-1alpha, VEGF, and
      TGF-beta in the VO-stressed heart. These data indicate that CS worsens VO
      remodeling by disrupting compensatory mechanisms, thereby promoting eccentric
      dilation and dysfunction.

PMID- 22153288
TI  - High prescription drug use and associated costs among Medicaid-eligible children
      with autism spectrum disorders identified by a population-based surveillance
      network.
AB  - PURPOSE: We assessed medication use and associated costs among 8- and 15-year-old
      children with autism spectrum disorders (ASD) identified by the South Carolina
      Autism and Developmental Disabilities Monitoring (SCADDM) Network. METHODS: All
      Medicaid-eligible SCADDM-identified children with ASD from surveillance years
      2006 and 2007 were included (n = 263). Children were classified as ASD cases when
      documented behaviors consistent with the DSM-IV-TR criteria for autistic
      disorder, Asperger disorder, or pervasive developmental disorder-not otherwise
      specified were present in health and education evaluation records. Medication and
      cost data were obtained by linking population-based and Medicaid data. RESULTS:
      All 263 SCADDM-identified children had Medicaid data available; 56% (n = 147) had
      a prescription of any type, 40% (n = 105) used psychotropic medication, and 20%
      (n = 52) used multiple psychotropic classes during the study period. Common
      combinations were (1) attention deficit hyperactivity disorder medications and an
      antihypertensive, antidepressant or antipsychotic; and (2) antidepressants and an
      antipsychotic. Multiple psychotropic classes were more common among older
      children. Both the overall distribution of the number of prescription claims and
      medication costs varied significantly by age. CONCLUSIONS: Results confirm that
      medication use in ASD, alone or in combination, is common, costly, and may
      increase with age.

PMID- 22153289
TI  - Who gets tattoos? Demographic and behavioral correlates of ever being tattooed in
      a representative sample of men and women.
AB  - PURPOSE: Despite recent increases in the popularity of tattooing, little is known
      about the prevalence and characteristics of adults who have ever been tattooed.
      We investigated demographic and behavioral correlates of ever getting tattooed in
      an adult population. METHODS: Computer-assisted telephone interviews were
      completed by a representative sample of 8656 men and women ages 16-64 years in
      Australia. RESULTS: A total of 14.5% of respondents had ever been tattooed, and
      2.4% of respondents had been tattooed in the year before the interview. Men were
      more likely than women to report a tattoo, but the highest rates of tattooing
      were found among women in their 20s (29.4%). Men and women ages 20-39 were most
      likely to have been tattooed, as were men with lower levels of education,
      tradesmen, and women with live-out partners. Tattooing was also associated with
      risk-taking behaviours, including smoking, greater numbers of lifetime sexual
      partners, cannabis use (women only) and ever having depression (men only).
      CONCLUSIONS: Tattooing has increased in popularity during the past decade. Yet
      tattoos still appear to be a marker for risk-taking behavior in adults.

PMID- 22153290
TI  - The one-stage autothermal thermophilic aerobic digestion for sewage sludge
      treatment: stabilization process and mechanism.
AB  - Batch experiment was carried out in a simulated thermophilic aerobic digester to
      investigate the digestion process of one-stage autothermal thermophilic aerobic
      digester and to explore the sludge stabilization mechanism. Volatile solids
      removal was 38.4% at 408 h and 45.0% at 552 h. Chemical oxidation demand, total
      nitrogen, and ammonia nitrogen in supernatant increased rapidly up to 168 h, and
      all of them fluctuated moderately after 360 h. Volatile fatty acid (VFA)
      accumulated rapidly up to 24 to 168 h, then declined sharply, reaching a low
      concentration after 312 h. Propionic, iso-valeric, and iso-butyric acids, in
      addition to acetic acids, were also the major components of VFA. As the
      biochemical metabolic process was inhibited under oxygen-deficiency condition,
      the digestion system can produce acetic, propionic, butyric acids and other VFA
      constituents to meet the demand for NAD(+) and maximize ATP generation. The ORP
      affected the VFA production and depletion as well as sulfate levels.

PMID- 22153291
TI  - Interaction of isothermal phase inversion and membrane formulation for pathogens
      detection in water.
AB  - The aim of this study was to explore the utilization of polymeric membrane for
      bio-sensing application in most efficient and rapid way. Customization of
      membrane formulation via phase separation study to modify its morphologies and
      properties enable the detection of different pathogens in a specific manner.
      Experimental findings (FESEM, through-pore distribution, porosity, capillary flow
      test and protein binding test) verified the predictions of faster capillary flow
      time and higher membrane's protein binding by the addition of cellulose acetate
      and nitrocellulose to the membrane casting dope, respectively. Throughout the
      phase separation study, the potential phase behavior was investigated, which was
      correlating various membrane structures to its performances for potential
      pathogens detection in water.

PMID- 22153292
TI  - Evaluation of a biologically-based filtration water reclamation plant for
      removing emerging contaminants: a pilot plant study.
AB  - The effect of hydraulic retention time (HRT), solar radiation and seasonality on
      the removal efficiency of 18 emerging contaminants has been studied in a
      biological filtration pilot plant based on Daphnia sp. The pilot plant consisted
      of a homogenization tank and two lines, A and B, each with four 1 m(3) tanks. One
      of these lines was directly exposed to sunlight whereas the other line was
      covered. Our results suggest that biodegradation and photodegradation are the
      most important removal pathways, whereas sorption makes a minor contribution. The
      removal efficiency ranged from no detectable removal to more than 90%. The
      kinetics of the degradation process was fit to a first order kinetic, with half
      lives from 0.6 to 42 days, depending on the particular compound. However, a
      scaling effect comes into play as the pilot plant was found to be more efficient
      than a similar full-scale polishing pond.

PMID- 22153293
TI  - Decolorization and biodegradation of azo dye, reactive blue 59 by aerobic
      granules.
AB  - The present study deals with development of aerobic granules from textile
      wastewater sludge and challenged with different concentration of reactive blue 59
      (RB59) to test their dye degradation potential. The granules efficiently degraded
      reactive blue 59 and also sustained higher dye loading of up to 5.0 g l(-1). The
      significant induction of enzymes azoreductase and cytochrome P-450 indicated
      their prominent role in the dye degradation while genotoxicity studies
      demonstrated that the biotransformed product of the dye as non-toxic. The
      microbial community of the textile dyes degrading aerobic sludge granules
      analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis
      (PCR-DGGE), revealed significantly diverse dye degrading microbial community
      belonging to alpha-, beta-, and gamma-proteobacteria.

PMID- 22153294
TI  - Estimating surface water concentrations of "down-the-drain" chemicals in China
      using a global model.
AB  - Predictions of surface water exposure to "down-the-drain" chemicals are presented
      which employ grid-based spatially-referenced data on average monthly runoff,
      population density, country-specific per capita domestic water and substance use
      rates and sewage treatment provision. Water and chemical load are routed through
      the landscape using flow directions derived from digital elevation data,
      accounting for in-stream chemical losses using simple first order kinetics.
      Although the spatial and temporal resolution of the model are relatively coarse,
      the model still has advantages over spatially inexplicit "unit-world" approaches,
      which apply arbitrary dilution factors, in terms of predicting the location of
      exposure hotspots and the statistical distribution of concentrations. The latter
      can be employed in probabilistic risk assessments. Here the model was applied to
      predict surface water exposure to "down-the-drain" chemicals in China for
      different levels of sewage treatment provision. Predicted spatial patterns of
      concentration were consistent with observed water quality classes for China.

PMID- 22153295
TI  - Metastatic esophageal adenocarcinoma of the great toe: a case report.
AB  - Owing to the rarity of metastatic disease to the bones of the foot, the
      guidelines for the proper care and workup of such conditions are inconsistent.
      The present case illustrates the evaluation of a patient with established
      esophageal adenocarcinoma that metastasized to involve the hallux, which had not
      been confirmed by previous imaging scans. The purpose of reporting the present
      case was to aid in establishing a protocol for a multidisciplinary approach to
      patient care and evaluating the entire body when performing metastatic disease
      treatment. As the present case has shown, evaluation of various abnormalities
      such as chronic paronychia could mask additional underlying conditions related to
      the patient's primary cancer.

PMID- 22153296
TI  - Subcutaneous rupture of the flexor hallucis longus tendon: a case report.
AB  - It is well known that rupture of the flexor hallucis longus tendon can be
      associated with open injuries and that closed rupture of the flexor hallucis
      longus tendon is rare. Tendon injuries of the foot can occur secondary to direct,
      indirect, or repetitive injury. Repetitive tendon injuries can cause tendinitis
      or stenosing tenosynovitis. Tendinitis is associated with internal tendon injury
      that can present with tendon thickening, mucinoid degeneration, nodule
      development, or in situ partial tears. Stenosing tenosynovitis is the development
      of tendon adhesions within the tendon sheath that interfere with tendon gliding,
      known as trigger toe. The flexor hallucis longus tendon is susceptible to injury
      along its entire course. A total of 35 cases of complete or partial closed
      ruptures of the flexor hallucis longus tendon have been reported. We present the
      case of complete subcutaneous rupture of the flexor hallucis longus tendon
      associated with trauma at the proximal phalangeal head.

PMID- 22153297
TI  - The impact of molecular manipulation in residue 114 of human immunodeficiency
      virus type-1 reverse transcriptase on dNTP substrate binding and viral
      replication.
AB  - Human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) has a
      unique tight binding to dNTP substrates. Structural modeling of Ala-114 of HIV-1
      RT suggests that longer side chains at this residue can reduce the space normally
      occupied by the sugar moiety of an incoming dNTP. Indeed, mutations at Ala-114
      decrease the ability of RT to synthesize DNA at low dNTP concentrations and
      reduce the dNTP-binding affinity (K(d)) of RT. However, the K(d) values of WT and
      A114C RT remained equivalent with an acyclic dNTP substrate. Finally, mutant A114
      RT HIV-1 vectors displayed a greatly reduced transduction in nondividing human
      lung fibroblasts (HLFs), while WT HIV-1 vector efficiently transduced both
      dividing and nondividing HLFs. Together these data support that the A114 residue
      of HIV-1 RT plays a key mechanistic role in the dNTP binding of HIV-1 RT and the
      unique viral infectivity of target cell types with low dNTP pools.

PMID- 22153299
TI  - Characterization of a monoclonal anti-capsid antibody that cross-reacts with
      three major primate lentivirus lineages.
AB  - Mouse monoclonal antibodies with varying specificities against the Gag capsid of
      simian and human immunodeficiency virus (SIV/HIV) were generated by immunizing
      mice with whole inactivated SIVagmTYO-1. Monoclonal antibody AG3.0 showed the
      broadest reactivity recognizing the Gag capsid protein (p24-27) and Gag
      precursors p38, p55, and p150 of HIV-1, HIV-2, SIVmac, and SIVagm. Using
      overlapping peptides, the AG3.0 epitope was mapped in capsid to a sequence
      (SPRTLNA) conserved among HIV-1, HIV-2, SIVrcm, SIVsm/mac, and SIVagm related
      viruses. Because of its broad cross-reactivity, AG3.0 was used to develop an
      antigen capture assay with a lower detection limit of 100 pg/ml HIV-1 Gag p24.
      Interestingly, AG3.0 was found to have a faster binding on/off rate for SIVagmVer
      and SIVmac Gag than for SIVagmSab Gag, possibly due to differences outside the
      SPRTLNA motif. In addition, the ribonucleic acid (RNA) coding for AG3.0 was
      sequenced to facilitate the development of humanized monoclonal antibodies.

PMID- 22153298
TI  - Conservation of the DENV-2 type-specific and DEN complex-reactive antigenic sites
      among DENV-2 genotypes.
AB  - The envelope (E) protein is composed of three domains (ED1, ED2 and ED3) with ED3
      targeted by the most potent neutralizing antibodies. DENV-2 strains can be
      divided into six genotypes. Comparison of ED3 of representative strains of the
      six genotypes revealed that there are nine variable residues that are specific to
      a given genotype. Recombinant ED3s (rED3s) of six different DENV-2 strains
      representing all nine variable residues were expressed, and their reactivity
      against a panel of two DENV-2 type-specific and three DENV complex-reactive
      monoclonal antibodies (mAbs) were compared. The differences in binding affinity
      to the rED3s representing different DENV-2 genotypes were relatively small, with
      the exception of type-specific-mAb 3H5 that showed up to 10-fold differences in
      binding between genotypes. Overall the binding differences did not lead to
      detectable differences in neutralization. Based on these results, DENV-2 ED3
      specific neutralizing antibodies will likely be effective against DENV-2 strains
      from all six genotypes.

PMID- 22153300
TI  - Mortality in first-contact psychosis patients in the U.K.: a cohort study.
AB  - BACKGROUND: The excess mortality following first-contact psychosis is well
      recognized. However, the causes of death in a complete incidence cohort and
      mortality patterns over time compared with the general population are unknown.
      METHOD: All 2723 patients who presented for the first time with psychosis in
      three defined catchment areas of the U.K. in London (1965-2004, n=2056),
      Nottingham (1997-1999, n=203) and Dumfries and Galloway (1979-1998, n=464) were
      traced after a mean of 11.5 years follow-up and death certificates were obtained.
      Data analysis was by indirect standardization. RESULTS: The overall standardized
      mortality ratio (SMR) for first-contact psychosis was 184 [95% confidence
      interval (CI) 167-202]. Most deaths (84.2%, 374/444) were from natural causes,
      although suicide had the highest SMR (1165, 95% CI 873-1524). Diseases of the
      respiratory system and infectious diseases had the highest SMR of the natural
      causes of death (232, 95% CI 183-291). The risk of death from diseases of the
      circulatory system was also elevated compared with the general population (SMR
      139, 95% CI 117-164) whereas there was no such difference for neoplasms (SMR 111,
      95% CI 86-141). There was strong evidence that the mortality gap compared with
      the general population for all causes of death (p<0.001) and all natural causes
      (p=0.01) increased over the four decades of the study. There was weak evidence
      that cardiovascular deaths may be increasing relative to the general population
      (p=0.07). CONCLUSIONS: People with first-contact psychosis have an overall
      mortality risk that is nearly double that of the general population. Most excess
      deaths are from natural causes. The widening of the mortality gap over the last
      four decades should be of concern to all clinicians involved in delivering
      healthcare.

PMID- 22153301
TI  - Chlamydophila psittaci subclinical infection in chronic polyarthritis.
AB  - OBJECTIVES: Recent evidence indicates that Chlamydophila psittaci (Cp) may
      establish chronic infections, which may promote autoimmunity and/or B cell
      lymphoproliferation. METHODS: The presence of a subclinical Cp infection was
      investigated in 293 patients with chronic inflammatory polyarthritis, including
      175 patients with rheumatoid factor (RF)-positive and/or anti-CCP-positive
      rheumatoid arthritis (RA) and 118 with seronegative polyarthritis (46 RF
      negative/anti-CCP-negative RA, 36 psoriatic arthritis and 36 undifferentiated
      spondyloarthritis). One hundred and eighty-five healthy controls were also
      investigated. The presence of Cp infection was assessed in peripheral blood
      mononuclear cells using several PCR protocols targeting different regions of the
      Cp genome (16S-23S spacer rRNA, OMP-A, and Gro-EL). The DNA of other Chlamydia
      species (C. Pneumoniae and C. Trachomatis) was also investigated. Amplicons were
      sequenced to confirm the specificity of PCR products. RESULTS: The presence of a
      subclinical chronic Cp infection was observed in a significantly higher
      percentage of patients with chronic polyarthritis (38/293; 13%) compared to
      healthy controls (1/185, 0.5%; OR=27.4, 95%CI:3.73-201.6, p<0.0001). Furthermore,
      the prevalence of Cp was higher in seronegative polyarthritis (23/118; 19.5%)
      than in seropositive RA patients (15/175; 7.4%; OR=2.58, 95%CI: 1.28-5.19,
      p=0.0078). The highest prevalence of Cp infection was found in RF/anti-CCP double
      negative RA patients (13/46, 28.3%), followed by patients with psoriatic
      arthritis (6/36; 16.7%). No differences in age, sex, disease duration and
      undergoing therapies were noticed between Cp-positive and Cp-negative patients;
      nor between seropositive and seronegative patients. CONCLUSIONS: Cp may be an
      infectious trigger possibly involved in the pathogenesis of a fraction of
      inflammatory polyarthritis, particularly in seronegative patients.

PMID- 22153302
TI  - Early cytotoxic and genotoxic effects of atrazine on Wistar rat liver: a
      morphological, immunohistochemical, biochemical, and molecular study.
AB  - Risk assessments suggest that intermediate and long-term exposure to triazine
      herbicides and its metabolites through water can cause severe damage to human
      health. The objective of this study was to investigate the possible effects of
      atrazine on Wistar rats submitted to subacute treatment. For this purpose, the
      activity of catalase and alanine aminotransferase was quantified, and the effect
      of the herbicide on cell membranes was examined based on the measurement of lipid
      peroxidation and consequent formation of malondialdehyde and on the mRNA
      expression of antioxidant enzymes (Mn-superoxide dismutase [SOD] and GSTM1) and
      connexins. In addition, we evaluated histopathological alterations in the liver,
      cellular expression of SOD and glutathione (GST), activation of heat shock
      proteins (HSPs) by immunohistochemistry, and the induction of apoptosis. The
      genotoxic potential of the herbicide was investigated by the micronucleus test in
      bone marrow smears. Adult male Wistar rats were treated with an aqueous solution
      of atrazine at a concentration of 400mg/kg/day, by gavage, for 14 consecutive
      days. Control groups were also included. The results showed an increase of
      catalase levels and maintenance of the expression of antioxidant enzymes (SOD and
      GST). In addition, lipid peroxidation, hepatic tissue degeneration, activation of
      HSP90, increased levels of connexin mRNA, and genotoxicity were observed. In
      conclusion, atrazine induced early hepatic oxidative stress that triggered
      defense mechanisms to maintain the morphophysiological integrity of the liver.
      Further studies are needed to better understand the effects of this herbicide on
      human health.

PMID- 22153303
TI  - NMR-based characterization of the acute metabolic effects of weathered crude and
      dispersed oil in spawning topsmelt and their embryos.
AB  - Oil spill responders require information on the relative toxicity of dispersed
      and un-dispersed oil in order to make informed decisions regarding the use of
      chemical dispersants during spill events. Toxicity of the water-accommodated
      fraction (WAF) and the chemically-enhanced WAF (CEWAF; via the dispersant Corexit
      9500) of weathered Prudhoe Bay crude oil was investigated using adult and
      embryonic topsmelt; topsmelt are an ecologically important atherinid in
      California bays and estuaries and an important indicator species. Following 96-h
      exposures, metabolite profiles were measured using 1D (1)H nuclear magnetic
      resonance (NMR) spectroscopy and compared via principal component analysis.
      Similar metabolic profiles were obtained between WAF- and CEWAF-exposed adults
      and embryos. Although metabolic changes, for the adults lacked significance,
      significant increasing and decreasing metabolic changes were observed for embryos
      directly exposed. Furthermore, no mortality was observed for embryos, exposed to
      WAF and normal development occurred, whereas CEWAF exposed embryos lead to
      mortality and cardiovascular abnormalities. Observed toxicological information,
      specifically for developing fish, can aide resource managers in the relative risk
      of treating oil spills with dispersant.

PMID- 22153304
TI  - Residue dynamics of pyraclostrobin in peanut and field soil by QuEChERS and LC
      MS/MS.
AB  - A modified QuEChERS-LC-MS/MS (acronym of quick, easy, cheap, effective, rugged
      and safe-liquid chromatography tandem mass spectrometry) method for the analysis
      of pyraclostrobin residue in peanut and soil was developed and validated.
      Pyraclostrobin residue dynamics and final residues in supervised field trials at
      Good Agricultural Practice (GAP) conditions in peanut and soil were studied. The
      limits of quantitation (LOQs) for pyraclostrobin in soil, plant, shell and peanut
      samples were 0.00057, 0.00026, 0.003 and 0.0037 mg kg(-1), respectively. At
      fortification levels of 0.005, 0.05 and 0.5 mg kg(-1) in all samples, it was
      shown that recoveries ranged from 80.3% to 109.4% with relative standard
      deviations of 1.1-8.2% (n=5). The dissipation experiments showed the half-lives
      (T(1/2)) of pyraclostrobin in soil and plants were 13.1-16.5 days and 10.3-11.2
      days, respectively. At pre-harvest intervals (PHI) of 14, 21 and 28 days,
      pyraclostrobin residue were 0.005-0.20 mg kg(-1) in soil, 0.006-0.27 mg kg(-1) in
      plants, below 0.053 mg kg(-1) in shells and not detectable in peanuts.

PMID- 22153305
TI  - The location of organotins within the erythrocyte membrane in relation to their
      toxicity.
AB  - The aim of the present study on organotin compounds, which are toxic to
      biological systems, was to determine the relationship between the compounds'
      toxicity and their location in the lipid bilayer of the biological membrane. It
      was assumed that the degree of disturbance caused within the lipid bilayer of the
      membrane, which in turn depends on the depth of incorporation, was an appropriate
      measure of toxicity. Previous results from our studies on the effect of organotin
      chlorides on membranes, made by using infrared radiation and hemolysis of
      erythrocytes, indicated that tributyltin (TBT) is the most active in terms of its
      interaction with the erythrocyte membrane. This compound causes the most severe
      hemolysis of erythrocytes and dehydration of membrane constituents. In order to
      connect the changes induced within the membrane structure with the compounds'
      location, we have investigated erythrocyte shape changes using both microscopic
      and fluorimetric methods. The microscopic results show that organotin compounds
      accumulate in the outer monolayer of the membrane. The fluorimetric studies
      indicate that all the compounds are present in the hydrophilic part of the outer
      lipid monolayer, and change the order parameter of the layer. However, only
      tributyltin, by being incorporated into the hydrophobic region of the monolayer,
      changes the fluidity in the alkyl chain region of the erythrocyte membrane.
      Furthermore, only TBT is present in both the hydrophilic and hydrophobic regions,
      as evidenced by the changed order parameter of the polar groups and fluorescence
      anisotropy of DPH probe in the hydrophobic region, these being connected with its
      high toxicity.

PMID- 22153306
TI  - Sensitivity, variability, and recovery of functional and structural endpoints of
      an aquatic community exposed to herbicides.
AB  - A mesocosm study with three photosystem-II inhibitors and an equipotent mixture
      was performed to address the value of functional and structural endpoints in
      evaluating the impact of herbicides on aquatic systems. The herbicides atrazine,
      diuron, and isoproturon were dosed in the ratio of their relative potencies as
      HC30 for the single substance treatments and as 1/3 HC30 for the mixture
      treatment to obtain comparable effect concentrations. To investigate the effects
      of the three herbicides and their mixture on photosynthesis of the whole system,
      the physical-chemical parameters pH, dissolved oxygen, and conductivity were
      monitored. To address effects on photosynthesis more specifically, the
      photosynthetic efficiency of phytoplankton and three submersed macrophytes
      (Elodea canadensis, Myriophyllum spicatum, and Potamogeton lucens) were
      investigated applying in vivo chlorophyll fluorescence as an indicator for their
      activity. As a structural endpoint, the species abundance and community structure
      of the phytoplankton community was determined. Effects were continuously
      monitored over a five week period of constant exposure, and during a 3 month post
      exposure period. The sensitivity, expressed as maximum effect during constant
      exposure, was higher for the structural parameters (total and single species
      abundances and PRC) than for the functional parameters. The mean coefficient of
      variation (CV) for the physical-chemical parameters was below 10%, for the
      photosynthesis measurement of the phytoplankton and macrophytes below 10 and 30%,
      respectively. Structural parameters, however, yielded higher variability with
      mean CVs for phytoplankton abundance data and single sensitive species reaching
      up to 96%. Effects on the phytoplankton photosynthesis measured via in vivo
      chlorophyll fluorescence were constant during the exposure period; whereas
      macrophytes recovered quickly from photosynthesis inhibition despite constant
      exposure. Effects on total system photosynthesis, determined via physical
      chemical parameters, lasted for a shorter period than for the phytoplankton
      photosynthesis demonstrating the importance of the macrophytes for total primary
      production. Thus, the evaluation of effects on communities in model ecosystems
      such as micro- and mesocosms should not be based on structural endpoints only due
      to their comparably high inherent variability. Instead, we recommend
      complementing the risk assessment with data obtained from sensitive functional
      endpoints addressing the specific mode of action of the respective compound for
      the most sensitive group of organisms to avoid over-estimation of the recovery
      potential of the aquatic system.

PMID- 22153307
TI  - Effects of indomethacin and propranolol on Chironomus riparius and Physella
      (Costatella) acuta.
AB  - New analytical methods are available for detecting novel xenobiotic compounds in
      freshwater systems. Pharmaceuticals are suspected of having effects on freshwater
      biota at very low concentrations, although the nature of these effects remains
      unclear. Previous data from the Llobregat River revealed a positive statistical
      relationship between the biomass of benthic macroinvertebrates and the presence
      of certain non-steroidal anti-inflammatory drugs (NSAIDs) and beta-blockers.
      Here, experiments were conducted with the midge Chironomus riparius and the
      freshwater snail Physella (Costatella) acuta in sediments and water,
      respectively. The sediments and water were treated with the pharmaceuticals
      propranolol and indomethacin, with the aims of assaying the effects of these
      compounds on the organisms and testing the statistical relationships observed in
      field. The variables measured were survival; C. riparius biomass; and the
      carbon/nitrogen ratio, lipid content and fertility of freshwater snails.
      Indomethacin in treated sediments induced an increase in C. riparius biomass,
      whereas propranolol inhibited growth, albeit at marginal statistical
      significance. By contrast, indomethacin in water had no effect on any of the
      parameters measured in P. acuta.

PMID- 22153308
TI  - [Rotational atherectomy in the drug-eluting stent era: a recent single-center
      experience].
AB  - INTRODUCTION: Percutaneous coronary intervention (PCI) of heavily calcified
      lesions is a challenge for the interventional cardiologist and is associated with
      a high rate of restenosis and target lesion revascularization (TLR). Adequate
      lesion preparation by rotational atherectomy followed by drug-eluting stent
      implantation has shown favorable results. OBJECTIVE: To report the recent
      experience of our center with rotational atherectomy (RA) of complex and heavily
      calcified coronary lesions. METHODS: We retrospectively analyzed consecutive
      patients who underwent PCI with RA in our center between January 2009 and
      December 2010. A total of 42 patients were included, 65% of whom had been
      previously refused for coronary artery bypass grafting due to unfavorable
      coronary anatomy or high surgical risk. RA was performed using the standard
      Boston Scientific Rotablator((r)) system. The procedure was performed ad-hoc in
      50% of patients and transradial access was used in 35%. Data were collected on
      immediate post-procedural events and major cardiac events during follow-up -
      cardiovascular death, myocardial infarction, TLR and recurrent angina. RESULTS:
      Of 1650 PCIs performed in a 23-month period from January 2009, 42 (2.5%) involved
      RA, a total of 42 patients (mean age 70.3+/-10.1 years, 67% male, 55% diabetic),
      three of whom had left main disease, six had three-vessel disease, 18 had two
      vessel disease and the other 15 had single-vessel disease. Of the lesions
      treated, 71% were >20 mm long and classified in 69% of cases as type C according
      to the ACC/AHA lesion classification, 4% being chronic total occlusions. The left
      anterior descending artery was treated in 56% of the procedures. The mean number
      of burrs used per lesion was 1.3 and a total of 69 stents were implanted, 81% of
      which were drug-eluting. During follow-up three patients had recurrent angina,
      one required TLR and two died due to a cardiovascular event. There was
      significant clinical improvement in 83% of patients. CONCLUSIONS: This study
      demonstrates that rotational atherectomy followed by stenting in heavily
      calcified lesions can nowadays be performed with high success rates and few
      complications, extending the possibility of coronary revascularization to a
      greater number of patients.

PMID- 22153309
TI  - [Rotational atherectomy in the drug-eluting stent era: the revival of a forgotten
      technique?].

PMID- 22153310
TI  - [Dyspnea in aortic stenosis: appearances can be deceptive].
AB  - Valvular aortic stenosis is the most common valvular disorder in Europe. Although
      recommended, stress exams are still underused in its evaluation. We report the
      case of a 60-year-old man who, following a routine electrocardiogram with
      abnormal ventricular repolarization, underwent stress testing, which was positive
      for myocardial ischemia, and an echocardiogram that revealed moderate aortic
      stenosis. Cardiac catheterization showed no angiographic coronary lesions and an
      intraventricular gradient of 45 mmHg. In view of the latter, stress
      echocardiography was performed, which documented an increase in the
      intraventricular gradient from 30 mmHg to 131 mmHg. Repeat stress
      echocardiography under treatment with bisoprolol showed an increase in test
      duration and a maximum intraventricular gradient at peak exercise of 36 mmHg.
      Stress exams may have an important role in the diagnostic and therapeutic
      management of patients with aortic stenosis.

PMID- 22153311
TI  - [A case of native valve infective endocarditis in an immunocompromised patient].
AB  - Infective endocarditis continues to be associated with high mortality, despite
      the medical and surgical therapeutic options available. Surgical intervention is
      indicated in cases of heart failure or uncontrolled infection and sometimes for
      the prevention of embolic phenomena. The authors present the case of a 56-year
      old male patient, with fibro-calcific mitral-aortic valve disease, splenectomized
      and with recently relapsed Hodgkin's lymphoma, who was admitted with infective
      endocarditis due to Streptococcus dysgalactiae. On the thirtieth day of directed
      antibiotic therapy, the mitral vegetation showed a significant increase in size
      and mobility. Surgery was considered at this point. However, given the patient's
      clinical stability and laboratory results, it was decided to adopt a conservative
      approach and to extend antibiotic therapy. The vegetation had regressed
      considerably seven days later. Given this atypical vegetation behavior, with
      slower than usual regression for the causative agent, the authors suggest that
      antibiotic therapy should be extended in patients with some degree of
      immunosuppression.

PMID- 22153312
TI  - [Mycotic aneurysm of the left ventricular free wall complicating aortic valve
      endocarditis].
AB  - We report the case of a 34-year-old man with aortic valve infective endocarditis
      caused by methicillin-resistant Staphylococcus aureus, complicated by an aortic
      annular abscess. A 23-mm St. Jude HP aortic mechanical prosthesis was implanted.
      The pre-discharge echocardiogram revealed a mycotic aneurysm of the basal
      posteroinferior wall, confirmed by cardiac magnetic resonance imaging, and it was
      decided to reintervene. The aneurysm was closed with a patch and the mitral valve
      had to be replaced. Although a small leak from the aneurysm patch persisted on
      the pre-discharge transthoracic echocardiogram, there was no trace of the
      aneurysm at nine-month re-evaluation. This case illustrates a rare complication
      of aortic valve endocarditis and shows the evolution of the mycotic aneurysm
      after closure via a transmitral approach.

PMID- 22153313
TI  - Use of an endoscopy face mask in patients with gastric distention undergoing
      noninvasive ventilation for acute respiratory failure: a comparative case study
      report.
AB  - We describe the use of an endoscopy face mask with a perforated membrane, which
      allows a nasogastric tube for continuous noninvasive ventilation in acute
      hypercapnic respiratory failure, in 2 patients who developed gastric distention.
      This interface was able to avoid most nonintentional  leaks through the mask, as
      compared with a conventional approach, improving ventilation efficiency. To our
      knowledge, this is the first case report of an endoscopy face mask used in
      noninvasive ventilation for this specific side effect.

PMID- 22153314
TI  - Effect of preoperative duration of stromal edema in bullous keratopathy on early
      visual acuity after endothelial keratoplasty.
AB  - PURPOSE: To clarify the relationship between visual acuity after Descemet
      stripping automated endothelial keratoplasty (DSAEK) and the preoperative
      duration of stromal edema. SETTING: Yamaguchi University Hospital, Yamaguchi,
      Japan. DESIGN: Comparative case series. METHODS: Patients who had DSAEK were
      divided into 2 groups based on whether the preoperative duration of stromal edema
      was less than 12 months (Group A) or more than 12 months (Group B). No patient
      had postoperative conditions that might have affected postoperative visual
      outcomes. Postoperatively, the corrected distance visual acuity (CDVA) was
      measured and the morphology of the anterior cornea evaluated by in vivo laser
      confocal microscopy. RESULTS: The postoperative CDVA in Group A ranged from 20/50
      to 20/16 at 3 months and from 20/66 to 20/16 at 6 months; the maximum CDVA was
      20/40 to 20/13. The postoperative CDVA in Group B ranged from 20/66 to 20/40 at 3
      months and 6 months; the maximum CDVA was 20/66 to 20/33. The structure of the
      anterior cornea was normal in patients in Group A but was abnormal with
      fibroblastic cells in the anterior stroma in patients in Group B. CONCLUSIONS:
      Patients with a preoperative duration of stromal edema of more than 12 months had
      pathologic changes in the corneal stroma that may have adversely affected visual
      acuity after DSAEK. Given that stromal edema, including that associated with
      bullous keratopathy, has been proposed to be a progressive condition, DSAEK may
      be most effective when performed early after the onset of edema, before the
      occurrence of pathologic changes in the stroma.

PMID- 22153315
TI  - Intraoperative performance and postoperative outcome comparison of longitudinal,
      torsional, and transversal phacoemulsification machines.
AB  - PURPOSE: To compare the intraoperative performance and postoperative outcomes of
      3 phacoemulsification machines that use different modes. SETTING: Kensington Eye
      Institute, Toronto, Ontario, Canada. DESIGN: Comparative case series. METHODS:
      This chart and video review comprised consecutive eligible patients who had
      phacoemulsification by the same surgeon using a Whitestar Signature Ellips-FX
      (transversal), Infiniti-Ozil-IP (torsional), or Stellaris (longitudinal) machine.
      RESULTS: The review included 98 patients. Baseline characteristics in the groups
      were similar; the mean nuclear sclerosis grade was 2.0 +/- 0.8. There were no
      significant intraoperative complications. The torsional machine averaged less
      phacoemulsification needle time (83 +/- 33 seconds) than the transversal (99 +/-
      40 seconds; P=.21) or longitudinal (110 +/- 45 seconds; P=.02) machines; the
      difference was accentuated in cases with high-grade nuclear sclerosis. The
      torsional machine had less chatter and better followability than the transversal
      or longitudinal machines (P<.001). The torsional and longitudinal machines had
      better anterior chamber stability than the transversal machine (P<.001).
      Postoperatively, the torsional machine yielded less central corneal edema than
      the transversal (P<.001) and longitudinal (P=.04) machines, corresponding to a
      smaller increase in mean corneal thickness (torsional 5%, transversal 10%,
      longitudinal 12%; P=.04). Also, the torsional machine had better 1-day
      postoperative visual acuities (P<.001). CONCLUSIONS: All 3 phacoemulsification
      machines were effective with no significant intraoperative complications. The
      torsional machine outperformed the transversal and longitudinal machines, with a
      lower mean needle time, less chatter, and improved followability. This
      corresponded to less corneal edema 1 day postoperatively and better visual
      acuity.

PMID- 22153316
TI  - The influence of chronic stress imposed on pregnant rats on the induced bone loss
      in their adult offspring.
AB  - BACKGROUND AND OBJECTIVE: Stress during pregnancy may alter offspring
      susceptibility to diseases during adulthood. In the present study, female Lewis
      rats were subjected to chronic stress during the gestational period, and the
      effect of this stress was evaluated histometrically on the progression of
      ligature-induced bone loss in their adult offspring. MATERIAL AND METHODS: After
      confirming pregnancy, half of the pregnant rats were randomly designated as
      control animals (no stress regimen was imposed), and the other half was submitted
      to a chronic stress model (immobilization at cold temperature) between the 7th
      and the 18th gestational day. After birth, 12 male rats delivered by stressed
      mothers - Group 1 (G1) - and 12 male rats delivered by non-stressed mothers -
      Group 2 (G2) - were selected. When birthed rats reached 250 g of body weight, a
      silk ligature was placed around their maxillary right second molar in order to
      induce bone loss. The non-ligated left side served as a control. Sixty days
      later, these animals were sacrificed by anaesthetic overdose. After routine
      laboratorial processing, images of the histological sections were digitized and
      submitted for histometric measurement using two parameters: histological
      attachment loss and bone loss. RESULTS: On the ligated side, G1 presented with
      greater histological attachment and bone loss than G2 (p<0.05). On the non
      ligated control side, neither of the groups presented with alterations in these
      parameters (p>0.05). CONCLUSION: The chronic stress regimen imposed on pregnant
      rats produced a greater progression of ligature-induced bone loss in their adult
      offspring.

PMID- 22153317
TI  - Salivary levels of antimicrobial peptides Hnp 1-3, Ll-37 and S100 in Behcet's
      disease.
AB  - BACKGROUND: Oral ulcer is the cardinal clinical sign and increased neutrophilic
      activity is a part of the pathogenesis in Behcet's disease (BD). Saliva, as a
      part of the innate immune response, contains antimicrobial peptides (AMPs) that
      are derived from both oral epithelial cells and neutrophils. The aim of this
      study was to investigate the associations between salivary levels of AMPs HNP 1
      3, LL-37 and S100 and disease course in patients with Behcet's disease (BD).
      METHODS: Fifty-three patients with BD and 44 healthy controls (HC) were included
      in the study. Disease severity score reflecting organ involvement was calculated.
      Salivary HNP 1-3, LL-37 and S100 levels were measured in unstimulated saliva
      samples by ELISA. RESULTS: Salivary HNP 1-3 and S100 levels in BD patients
      (2715.2 +/- 1333.4 MUg/ml and 430.6 +/- 203.9 ng/ml) were significantly higher
      compared to HC (1780.6 +/- 933.2 MUg/ml and 365.3 +/- 84.7 ng/ml) (p = 0.000 and
      p = 0.004, respectively). Although LL-37 levels were also higher in BD than HC
      (190.9 +/- 189.1 vs 143.1 +/- 128.9 ng/ml), no significant difference was
      observed (p = 0.53). Salivary HNP 1-3 and LL-37 levels were associated with the
      severity of BD (mild disease: 1975.1 +/- 1174.2 MUg/ml and 115.9 +/- 109.4 ng/ml
      vs severe disease: 2955.7 +/- 1305.6 MUg/ml and 215.3 +/- 203.8 ng/ml, p=0.020
      and p=0.031, respectively). Salivary LL-37 levels also correlated with the number
      of monthly oral ulcers (r = 0.5 p = 0.000). CONCLUSION: An increase in salivary
      HNP 1-3 and S100 levels might be associated with enhanced local and systemic
      innate responses in BD.

PMID- 22153318
TI  - The development of T cell-dominated inflammatory responses induced by sodium
      lauryl sulphate in mouse oral mucosa.
AB  - The effect of a single time exposure of SLS to the buccal mucosa of mice was
      compared to one application of the hapten OXA (oxazolone), evaluated by routine
      histology, immunohistochemistry and ELISA quantifications of cytokines. The SLS
      concentrations (2%, 4% and 8%) resulted in epithelial surface necrosis at 1-6 h,
      after 2-6 h accumulation of intra-epithelial neutrophils and at 24 h the main
      inflammatory cells were mononuclear. Increased concentrations of SLS gave more
      severe damage. CD4(+) T cells were found at 6 h and increased slightly up to 24 h
      and were most frequently seen at the lowest SLS dose. The CD8(+) T cells were
      kept at a low number during the whole 24 h observation period, but increased
      proportionally to the CD4(+) T cells. One application of 1% OXA did not raise the
      number of cells of either phenotype (2-24 h). Neither IL-2 nor IFN-gamma
      demonstrated increased levels during the week of observation at any concentration
      of SLS, contrary to one application of OXA which caused increased IL-2 levels
      both at the local application site and in the regional and distant lymph nodes.
      Regardless of SLS concentration, a minor increase in regional lymph node weight
      was observed 8-12 h after substance application, quickly to subside whilst one
      OXA application gave a maximal weight increase at 48-72 h. We conclude that oral
      mucosa irritant SLS reactions gave early surface necrosis and neutrophil
      infiltrations and later mononuclear cell infiltrations dominated by CD4(+) T
      cells. The cytokines IL-2 and IFN-gamma and lymphocyte proliferation in the
      regional lymph nodes was not observed after SLS application, contrary to hapten
      application.

PMID- 22153319
TI  - Morphological characterization of cardiac induced intracranial pressure (ICP)
      waves in patients with overdrainage of cerebrospinal fluid and negative ICP.
AB  - Symptomatic overdrainage of cerebrospinal fluid (CSF) can be seen in shunted
      hydrocephalus patients and in non-shunted patients with spontaneous intracranial
      hypotension (SIH). In these patients, intracranial pressure (ICP) monitoring
      often reveals negative static ICP, while it is less understood how the pulsatile
      ICP (cardiac induced ICP waves) is affected. This latter aspect is addressed in
      the present study. A set of 40 ICP recordings from paediatric and adult
      hydrocephalus patients were randomly selected. Each cardiac induced ICP wave was
      automatically identified and manually verified by the beginning and ending
      diastolic minimum pressures and the systolic maximum pressure. The ICP wave
      parameters (static pressure, amplitude, rise time, rise time coefficient,
      downward coefficient, wave duration, and area-under-curve) were then
      automatically computed. The material of 40 ICP recordings provided a total of
      3,192,166 cardiac induced ICP waves (1,292,522 in paediatric patients and
      1,899,644 in adult patients). No apparent changes in ICP wave parameters were
      seen when mean ICP became negative, except that the parameters amplitude, rise
      time coefficient, downward coefficient and area under curve somewhat increased
      when mean ICP was below -15 mmHg.

PMID- 22153320
TI  - LES of non-Newtonian physiological blood flow in a model of arterial stenosis.
AB  - Large Eddy Simulation (LES) is performed to study the physiological pulsatile
      transition-to-turbulent non-Newtonian blood flow through a 3D model of arterial
      stenosis by using five different blood viscosity models: (i) Power-law, (ii)
      Carreau, (iii) Quemada, (iv) Cross and (v) modified-Casson. The computational
      domain has been chosen is a simple channel with a biological type stenosis formed
      eccentrically on the top wall. The physiological pulsation is generated at the
      inlet of the model using the first four harmonic series of the physiological
      pressure pulse (Loudon and Tordesillas [1]). The effects of the various viscosity
      models are investigated in terms of the global maximum shear rate, post-stenotic
      re-circulation zone, mean shear stress, mean pressure, and turbulent kinetic
      energy. We find that the non-Newtonian viscosity models enlarge the length of the
      post-stenotic re-circulation region by moving the reattachment point of the shear
      layer separating from the upper wall further downstream. But the turbulent
      kinetic energy at the immediate post-lip of the stenosis drops due to the effects
      of the non-Newtonian viscosity. The importance of using LES in modelling the non
      Newtonian physiological pulsatile blood flow is also assessed for the different
      viscosity models in terms of the results of the dynamic subgrid-scale (SGS)
      stress Smagorinsky model constant, C(s), and the corresponding SGS normalised
      viscosity.

PMID- 22153321
TI  - Rigid versus flexible plate fixation for periprosthetic femoral fracture-computer
      modelling of a clinical case.
AB  - A variety of plate designs have been implemented for treatment of periprosthetic
      femoral fracture (PFF) fixation. Controversy, however, exists with regard to
      optimum fixation methods using these plates. A clinical case of a PFF fixation
      (Vancouver type C) was studied where a rigid locking plate fixation was compared
      with a more flexible non-locking approach. A parametric computational model was
      developed in order to understand the underlying biomechanics between these two
      fixations. The model was used to estimate the overall stiffness and fracture
      movement of the two implemented methods. Further, the differing aspects of plate
      design and application were incrementally changed in four different models. The
      clinical case showed that a rigid fixation using a 4.5 mm titanium locking plate
      with a short bridging length did not promote healing and ultimately failed. In
      contrast, a flexible fixation using 5.6 mm stainless steel non-locking plate with
      a larger bridging length promoted healing. The computational results highlighted
      that changing the bridging length made a more substantial difference to the
      stiffness and fracture movement than varying other parameters. Further the
      computational model predicted the failure zone on the locking plate. In summary,
      rigid fracture fixation in the case of PFF can suppress the fracture movement to
      a degree that prevents healing and may ultimately fail. The computational
      approach demonstrated the potential of this technique to compare the stiffness
      and fracture movement of different fixation constructs in order to determine the
      optimum fixation method for PFF.

PMID- 22153322
TI  - Wireless instrumentation system based on dry electrodes for acquiring EEG
      signals.
AB  - This paper presents a complete non-invasive Wireless acquisition system based on
      dry electrodes for electroencephalograms (WiDE-EEG) with emphasis in the
      electronic system design. The WiDE-EEG is composed by a 2.4 GHz radio-frequency
      (RF) transceiver, biopotential acquisition electronics and dry electrodes. The
      WiDE-EEG can acquire electroencephalogram (EEG) signals from 5 unipolar channels,
      with a resolution of 16 bits and minimum analog amplitude of 9.98 MUV(pp), at a
      sampling rate of 1000 samples/s/channel and sends them to a processing unit
      through RF in a 10 m range. The analog channels were optimized for EEG signals
      (with amplitudes in the range 70-100 MUV) and present the following
      characteristics: a signal gain of 66 dB and a common mode rejection ratio of 56.5
      dB. Each electrode is composed by 16 microtip structures that were fabricated
      through bulk micromachining of a <100>-type silicon substrate in a potassium
      hydroxide (KOH) solution. The microtips present solid angles of 54.7 degrees , a
      height of 100-200 MUm and 2 MUm spaced apart. The electrodes have a thin layer
      (obtained by sputtering) of iridium oxide (IrO) to guaranty their
      biocompatibility and improve the contact with the skin. These dry electrodes are
      in direct contact with the electrolyte fluids of the inner skin layers, and avoid
      the use of conductive gels. The complete WiDE-EEG occupies a volume of 9 cm*8.5
      cm*1 cm, which makes it suitable for true mobility of the subjects and at the
      same time allows high data transfer rates. Since the WiDE-EEG is battery-powered,
      it overcomes the need of galvanic isolation for ensuring patient safety observed
      on conventional EEG instrumentation systems. The WiDE-EEG presents a total power
      consumption of 107 mW, divided as follows: the acquisition system contributes
      with 10 mW per channel, whereas the commercial MICAz module contributes with 57
      mW (e.g., 24 mW from the microcontroller and 33 mW from the RF chip). The WiDE
      EEG also presents autonomy of about 25 h with two class AA 1.5 V batteries.

PMID- 22153323
TI  - Exploring perceptual processing of ASL and human actions: effects of inversion
      and repetition priming.
AB  - In this paper, we compare responses of deaf signers and hearing non-signers
      engaged in a categorization task of signs and non-linguistic human actions. We
      examine the time it takes to make such categorizations under conditions of 180
      degrees  stimulus inversion and as a function of repetition priming, in an effort
      to understand whether the processing of sign language forms draws upon special
      processing mechanisms or makes use of mechanisms used in recognition of non
      linguistic human actions. Our data show that deaf signers were much faster in the
      categorization of both linguistic and non-linguistic actions, and relative to
      hearing non-signers, show evidence that they were more sensitive to the
      configural properties of signs. Our study suggests that sign expertise may lead
      to modifications of a general-purpose human action recognition system rather than
      evoking a qualitatively different mode of processing, and supports the contention
      that signed languages make use of perceptual systems through which humans
      understand or parse human actions and gestures more generally.

PMID- 22153324
TI  - The ability of children to delay gratification in an exchange task.
AB  - The ability to wait for a reward is a necessary capacity for economic
      transactions. This study is an age-related investigation of children's ability to
      delay gratification in an exchange task requiring them to wait for a significant
      reward. We gave 252 children aged 2-4 a small piece of cookie, then offered them
      an opportunity to wait for a predetermined delay period before exchanging it for
      a larger one. In a first experiment, the children had to exchange the initial
      food item for rewards two, four or eight times larger. Results showed that
      children aged 3-4 years old sustained longer time lags for larger rewards than
      for smaller rewards. This effect was not found in 2-year-old subjects. In a
      second experiment, a reward 40 times larger than the initial piece was offered to
      determine the maximum waiting time that children could sustain. All age groups
      increased their performances. Older children were more successful at waiting, but
      some children as young as 2 years old were able to tolerate delays of up to 16
      min. Older children who chose to give up waiting earlier than their known
      capacity demonstrated anticipation skills which had not been seen in younger
      children, showing that they had anticipated an increase in the time lag, and that
      they had considered both time and reward value when making their decision.
      Despite the age effect, we did not establish any limits for delaying
      gratification in children. This study may have educational implications for
      dealing with behavioral misconduct, which is known to be related to impulsivity
      control in young children.

PMID- 22153325
TI  - Influence of veneer thickness on residual stress profile in veneering ceramic:
      measurement by hole-drilling.
AB  - OBJECTIVES: The veneering process of frameworks induces residual stresses and can
      initiate cracks when combined with functional stresses. The stress distribution
      within the veneering ceramic as a function of depth is a key factor influencing
      failure by chipping. This is a well-known problem with Yttria-tetragonal-zirconia
      polycrystal based fixed partial dentures. The objective of this study is to
      investigate the influence of veneer thickness on the stress profile in zirconia-
      and metal-based structures. METHODS: The hole-drilling method, often used for
      engineering measurements, was adapted for use with veneering ceramic. The stress
      profile was measured in bilayered disc samples of 20 mm diameter, with a 1 mm
      thick zirconia or metal framework. Different veneering ceramic thicknesses were
      performed: 1 mm, 1.5 mm, 2 mm, 2.5 mm and 3 mm. RESULTS: All samples exhibited
      the same type of stress vs. depth profile, starting with compressive at the
      ceramic surface, decreasing with depth up to 0.5-1.0 mm from the surface, and
      then becoming compressive again near the framework, except for the 1.5 mm
      veneered zirconia samples which exhibited interior tensile stresses. Stresses in
      the surface of metal samples were not influenced by veneer thickness. Variation
      of interior stresses at 1.2 mm from the surface in function of veneer thickness
      was inverted for metal and zirconia samples. SIGNIFICANCE: Veneer thickness
      influences in an opposite way the residual stress profile in metal- and in
      zirconia-based structures. A three-step approach and the hypothesis of the
      crystalline transformation are discussed to explain the less favorable residual
      stress development in zirconia samples.

PMID- 22153326
TI  - Novel dental composites reinforced with zirconia-silica ceramic nanofibers.
AB  - OBJECTIVE: To fabricate and characterize dental composites reinforced with
      various amounts of zirconia-silica (ZS) or zirconia-yttria-silica (ZYS) ceramic
      nanofibers. METHODS: Control composites (70 wt% glass particle filler, no
      nanofibers) and experimental composites (2.5, 5.0, and 7.5 wt% ZS or ZYS
      nanofibers replacing glass particle filler) were prepared by blending 29 wt%
      dental resin monomers, 70 wt% filler, and 1.0 wt% initiator, and polymerized by
      either heat or dental curing light. Flexural strength (FS), flexural modulus
      (FM), energy at break (EAB), and fracture toughness (FT) were tested after the
      specimens were stored in 37 degrees C deionized water for 24h, 3 months, or 6
      months. Degree of conversion (DC) of monomers in composites was measured using
      Fourier transformed near-infrared (FT-NIR) spectroscopy. Fractured surfaces were
      observed by field-emission scanning electron microscope (FE-SEM). The data were
      analyzed using ANOVA with Tukey's Honestly Significant Differences test used for
      post hoc analysis. RESULTS: Reinforcement of dental composites with ZS or ZYS
      nanofibers (2.5% or 5.0%) can significantly increase the FS, FM and EAB of dental
      composites over the control. Further increase the content of ZS nanofiber (7.5%),
      however, decreases these properties (although they are still higher than those of
      the control). Addition of nanofibers did not decrease the long-term mechanical
      properties of these composites. All ZS reinforced composites (containing 2.5%,
      5.0% and 7.5% ZS nanofibers) exhibit significantly higher fracture toughness than
      the control. The DC of the composites decreases with ZS nanofiber content.
      SIGNIFICANCE: Incorporation of ceramic nanofibers in dental composites can
      significantly improve their mechanical properties and fracture toughness and thus
      may extend their service life.

PMID- 22153327
TI  - Enabling children with Developmental Coordination Disorder to self-regulate
      through the use of Dynamic Performance Analysis: evidence from the CO-OP
      approach.
AB  - Anecdotal evidence suggests that Dynamic Performance Analysis (DPA) is learned by
      children with Developmental Coordination Disorder (DCD) during Cognitive
      Orientation to Occupational Performance (CO-OP) intervention. DPA is a tool used
      by therapists during the CO-OP approach to identify performance breakdowns and
      strategies for skill acquisition. This suggests that the self-regulation
      difficulties experienced by these children are amenable to intervention. The
      purpose of this proof of principle study was to determine: if school-aged
      children with DCD carry out DPAs, if DPA use was positively affected by
      intervention, and whether CO-OP had a larger effect on DPA use. Previously
      recorded videos of 13 children with DCD undergoing CO-OP, contemporary treatment
      or task-specific training were analyzed for evidence of DPA use. It was found
      that children in all three groups used simple DPAs before intervention; those
      receiving CO-OP intervention dramatically increased the number and quality of
      DPAs and could spontaneously apply it to the performance of another child. These
      findings indicate that, despite issues of self-regulation, children with DCD do
      self-monitor performance. More importantly, this ability can improve with CO-OP
      intervention as it guides the discovery of self-identified performance solutions,
      thereby enabling skill acquisition, generalization and transfer.

PMID- 22153328
TI  - [The role of informal care in individualized care plan delivery: a conditional
      choice for dependent people].
AB  - OBJECTIVES: To analyze the relationship between sociodemographic and health
      variables (including informal care) and the healthcare service delivery assigned
      in the individualized care plan. METHODS: An observational cross-sectional study
      was conducted in a representative sample of the dependent population in Cuenca
      (Spain) in February, 2009. Information was obtained on people with level II and
      III dependency. Four different logistic regression models were used to identify
      the factors associated with the care service delivery assigned in the
      individualized care plan. Independent variables consisted of age, gender, marital
      status, annual income, place of residence, health conditions, medical treatment,
      and perception of informal care. RESULTS: A total of 83.7% of the sample was
      assigned economic benefits and 15.3% were assigned services. Eighty percent of
      the sample received informal care in addition to dependency benefits. People who
      received informal care were 3239 times more likely to be assigned economic
      benefits than persons not receiving informal care. CONCLUSION: For the period
      analyzed (the first phase of the implementation of the Dependency Act), the
      variables associated with receiving economic benefits (versus services) were
      being married, having a high annual income, the place of residence (rural areas
      versus urban area), and receiving hygiene-dietary treatment and informal care.

PMID- 22153330
TI  - Simultaneous determination of catechin, epicatechin and epicatechin gallate in
      rat plasma by LC-ESI-MS/MS for pharmacokinetic studies after oral administration
      of Cynomorium songaricum extract.
AB  - A rapid and valid method was developed for simultaneous determination catechin,
      epicatechin and epicatechin gallate in rat plasmas using scopoletin (103 ng mL(
      1)) as an internal standard (IS). The separation was performed on Eclipse plus
      C18 column (100 mm * 4.6 mm, 1.8 MUm) at a flow rate of 0.3 mL min(-1), and
      acetonitrile-0.1% formic acid was used as mobile phase. The recoveries of three
      analytes and IS were more than 78.9%. The lower limits of quantitation (LLOQ) in
      rat plasma were 2.14, 2.38 and 2.08 ng mL(-1) respectively for catechin,
      epicatechin and epicatechin gallate. Intra-day and inter-day precisions were
      within 12%. The accuracies were more than 85%. After single oral administration
      of 15.25 g kg(-1) Cynomorium songaricum extract, C(max) of catechin, epicatechin
      and epicatechin gallate in rat plasma were respectively 86.69+/-38.65, 32.57+/
      15.00 and 36.93+/-12.62 ng mL(-1) while T(max) values were respectively 0.15+/
      0.09, 0.20+/-0.10 and 0.20+/-0.13 h. The results demonstrated that the present LC
      MS/MS method was sensitive enough for pharmacokinetic study of catichins
      following oral administration of C. songaricum extract.

PMID- 22153333
TI  - Non-ST-segment elevation acute coronary syndrome presenting with ST-segment
      elevation in aVR and dual antiplatelet therapy.

PMID- 22153331
TI  - Quality characteristics and fertilizing ability of ram sperm subpopulations
      separated by partition in an aqueous two-phase system.
AB  - Centrifugal countercurrent distribution (CCCD) in an aqueous two-phase system
      (TPS) is a resolute technique revealing sperm heterogeneity and for the
      estimation of the fertilizing potential of a given semen sample. However,
      separated sperm subpopulations have never been tested for their fertilizing
      ability yet. Here, we have compared sperm quality parameters and the fertilizing
      ability of sperm subpopulations separated by the CCCD process from ram semen
      samples maintained at 20 degrees C or cooled down to 5 degrees C. Total and
      progressive sperm motility was evaluated by computer-assisted analysis using a
      CASA system and membrane integrity was evaluated by flow cytometry by staining
      with CFDA/PI. The capacitation state, staining with chlortetracycline, and
      apoptosis-related markers, such as phosphatidylserine (PS) translocation detected
      with Annexin V, and DNA damage detected by the TUNEL assay, were determined by
      fluorescence microscopy. Additionally, the fertilizing ability of the
      fractionated subpopulations was comparative assessed by zona binding assay (ZBA).
      CCCD analysis revealed that the number of spermatozoa displaying membrane and DNA
      alterations was higher in samples chilled at 5 degrees C than at 20 degrees C,
      which can be reflected in the displacement to the left of the CCCD profiles. The
      spermatozoa located in the central and right chambers (more hydrophobic)
      presented higher values (P<0.01) of membrane integrity, lower PS translocation
      (P<0.05) and DNA damage (P<0.001) than those in the left part of the profile,
      where apoptotic markers were significantly increased and the proportion of viable
      non-capacitated sperm was reduced. We have developed a new protocol to recover
      spermatozoa from the CCCD fractions and we proved that these differences were
      related with the fertilizing ability determined by ZBA, because we found that the
      number of spermatozoa attached per oocyte was significantly higher for
      spermatozoa recovered from the central and right chambers, in both types of
      samples. This is the first time, to our knowledge that sperm recovered from a two
      phase partition procedure are used for fertilization assays. These results open
      up new possibilities for using specific subpopulations of sperm for artificial
      insemination or in vitro fertilization, not only regarding better sperm quality
      but also certain characteristics such as subpopulations enriched in spermatozoa
      bearing X or Y chromosome that we have already isolated or any other feature.

PMID- 22153332
TI  - Development and validation of a simple reversed-phase HPLC method for the
      determination of camptothecin in animal organs following administration in solid
      lipid nanoparticles.
AB  - A simple, sensitive and specific high-performance liquid chromatography (HPLC)
      assay for the quantification of camptothecin (CPT), a potent anticancer
      candidate, incorporated into solid lipid nanoparticles (SLN) in several rat
      organs (brain, heart, kidneys liver, lung, spleen) and serum was developed and
      validated. The sample pre-treatment involved organs homogenisation followed by
      CPT extraction. The samples were injected onto an analytical reversed-phase (RP)
      MediterraneaTM Sea18 column maintained at 30 degrees C. The chromatographic
      separation was achieved by gradient elution consisting of triethyamine buffer pH
      5.5 and acetonitrile at a flow rate of 1.2 mL/min in 16 min of run time and
      retention time of 9.8 min (lactone). Fluorescence detection was used at the
      excitation and emission of 360 and 440 nm, respectively. The calibration curves
      in the different organs, serum and in PB3 were linear (r(2)>0.9999) over CPT
      concentrations ranging from 1 to 200 ng/mL or 0.5 to 200 ng/mL (n=6),
      respectively. The method was shown to be specific, accurate (between 94.4+/-4.5%
      and 108.9+/-0.6%) and precise at the intra-day and inter-day levels as reflected
      by the coefficient of variation (CV<6.3%) at three different concentrations (10,
      50 and 100 ng/mL) in all matrices. Stability studies showed that CPT was stable
      in all matrices after 24h of incubation at room temperature (RT), after 24 h in
      the autosampler or after three freeze/thaw cycles. The mean recoveries of CPT in
      suspension, loaded into SLN and in a physical mixture with SLN at three
      concentrations of 10, 50 and 200 ng/mL were higher than 86.4%. The detection
      limit (DL) was <=0.2 ng/mL and the quantification limit (QL) was <=0.5 ng/mL. The
      method developed is reliable, precise and accurate and can be used in the
      determination of CPT amount in rat organ samples after i.v. administration of CPT
      in suspension, in physical mixture with SLN and incorporated in SLN.

PMID- 22153334
TI  - A user-friendly integrated monitor-adhesive patch for long-term ambulatory
      electrocardiogram monitoring.
AB  - BACKGROUND: Compliance to long-term ambulatory electrocardiogram monitoring is
      important for diagnosis in patients with cardiac arrhythmia. This requires a
      system with a minimal impact on daily activities. OBJECTIVE: The aim of this
      study was to investigate if a lightweight integrated adhesive monitor for long
      term use without unacceptable adverse effects is feasible. METHODS: The
      participants wore either a prototype lightweight monitor or a control system for
      a total of up to 30 days, changing patches once (investigational device) or twice
      (control) weekly. Comfort, skin irritation, and impact on quality of life were
      recorded. RESULTS: The new monitor can be worn by most participants for periods
      of at least 6 days. Skin irritation and comfort rating were comparable, and
      impact on the quality of life was low compared with the control. Patients
      considered the device comfortable. CONCLUSION: An integrated adhesive monitor
      that can be worn on the skin up to 7 days with minimal side effects is feasible.

PMID- 22153336
TI  - Modification of molecular sieves MCM-41 and SBA-15 with covalently grafted
      pyromellitimide and 1,4,5,8-naphthalenediimide.
AB  - This article describes the covalent grafting of pyromellitimide and 1,4,5,8
      naphthalenediimide, which are organic semiconductors with very interesting
      electro-optical properties, onto the walls of mesoporous molecular sieves. The
      mesoporous materials MCM-41 and SBA-15 were first treated with 3
      aminopropyltriethoxysilane, generating materials with a surface coverage of
      primary amino groups. These materials were further reacted with either
      pyromellitic dianhydride or 1,4,5,8-naphthalenetetracarboxylic dianhydride,
      generating surface-bound pyromellitimide or 1,4,5,8-naphthalenediimide,
      respectively. The success of the modification reactions was confirmed by
      elemental and thermogravimetric analyses, X-ray diffraction patterns and
      infrared, reflectance and fluorescence spectroscopies. The results indicated that
      the mesoporous structure of the new materials was preserved after the
      modification reactions and that the chromophores were included inside the
      mesoporous channels with stacked aromatic rings.

PMID- 22153335
TI  - Electrocardiographic, electrophysiologic, and anatomical features of ventricular
      tachycardia originating from noncoronary cusp.
AB  - In this article, we report 2 young patients (a 15-year-old adolescent girl and a
      25-year-old man) with drug-refractory palpitations. Admission electrocardiograms
      showed runs of ventricular tachycardia with left bundle-branch block morphology,
      left inferior axis, early precordial QRS transition, and positive QRS complex in
      lead I. In right ventricular mapping, the earliest activation site was found in
      the His bundle region. Aortic root mapping showed a very early fractionated
      ventricular signal with large atrial potential and no His potential in the
      noncoronary cusp region. Radiofrequency energy application in this region
      resulted in tachycardia termination within 5 to 10 seconds. During a 3- to 6
      month follow-up period, the patients remained asymptomatic, and the
      electrocardiogram showed no ventricular arrhythmias.

PMID- 22153337
TI  - Short range order at the amorphous TiO(2)-water interface probed by silicic acid
      adsorption and interfacial oligomerization: an ATR-IR and 29Si MAS-NMR study.
AB  - Adsorption and oligomerization of H(4)SiO(4) at the amorphous TiO(2)-aqueous
      interface were studied using in situ Attenuated Total Reflectance Infrared (ATR
      IR) and ex situ solid state (29)Si nuclear magnetic resonance (NMR). The ATR-IR
      spectra indicate that a monomeric silicate species is present at low silicate
      surface concentration (Gamma(Si)). Above a threshold Gamma(Si) linear silicate
      oligomers are formed and these oligomers dominate the surface at high Gamma(Si).
      Interestingly the ATR-IR spectra of H(4)SiO(4) on the TiO(2) surface are very
      similar to those previously observed on the poorly ordered iron oxide phase
      ferrihydrite. The (29)Si NMR spectrum of silicate on the TiO(2) surface shows the
      presence of Si in three states with chemical shifts corresponding to isolated
      monomers (Q(0)), the ends of linear oligomers (Q(1)) and the middle of linear
      oligomers (Q(2)). The ratio of the area of the Q(1) and Q(2) peaks was ~2:1 which
      is consistent with the proposed formation of linear silicate trimers by insertion
      of a solution H(4)SiO(4) between adjacent suitably orientated adsorbed silicate
      monomers. A structural interpretation indicates that the observed interfacial
      silicate oligomerization behavior is a general phenomenon whereby bidentate
      silicate monomers on oxide surfaces are disposed towards forming linear oligomers
      by condensation reactions involving their two terminal Si-OH groups. The high
      surface curvature of nanometer sized spheres inhibits the formation of
      interfacial silicates with a higher degree of polymerization.

PMID- 22153338
TI  - Synthesis and biological evaluation of novel derivatives of gambogic acid as anti
      hepatocellular carcinoma agents.
AB  - A series of novel derivatives of gambogic acid (GA) were synthesized and
      evaluated for their in vitro cytotoxicity against human hepatocellular carcinoma
      (HCC) cells. All derivatives showed better aqueous solubility than GA, and
      compounds 3a, 3e, and 3f displayed potent inhibition of HCC cell proliferation
      (IC(50): 0.045-0.59 MUM on Bel-7402 cells and 0.067-0.94 MUM on HepG2 cells)
      superior to GA and taxol. Additionally, the most potent compound 3e did not
      affect significantly the proliferation of non-tumor liver cells, suggesting that
      it might selectively inhibit HCC proliferation. Furthermore, 3e induced high
      frequency of Bel-7402 cell apoptosis. Our findings suggest that these novel GA
      derivatives may hold a great promise as therapeutic agents for the intervention
      of human HCC.

PMID- 22153339
TI  - Novel poly(ADP-ribose) polymerase-1 inhibitors.
AB  - Synthesis and activity of a series of 3-aroyl-derived analogs of novel
      pyrrolocarbazole 1 as poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are
      disclosed.

PMID- 22153340
TI  - Discovery of potent and selective matrix metalloprotease 12 inhibitors for the
      potential treatment of chronic obstructive pulmonary disease (COPD).
AB  - Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease
      associated with irreversible progressive airflow limitation. Matrix
      metalloproteinase-12 (MMP-12) has been characterized to be one of the major
      proteolytic enzymes to induce airway remodeling, destruction of elastin and the
      aberrant remodeling of damaged alveoli in COPD and asthma. The goal of this
      project is to develop and identify an orally potent and selective small molecule
      inhibitor of MMP-12 for treatment of COPD and asthma. Syntheses and structure
      activity relationship (SAR) studies of a series of dibenzofuran (DBF)
      sulfonamides as MMP-12 inhibitors are described. Potent inhibitors of MMP-12 with
      excellent selectivity against other MMPs were identified. Compound 26 (MMP118),
      which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling
      inflammation and lung inflammation mouse models, had been successfully advanced
      into Development Track status.

PMID- 22153341
TI  - Effect of a second nitroimidazole redox centre on the accumulation of a hypoxia
      marker: synthesis and in vitro evaluation of 99mTc-labeled bisnitroimidazole
      propylene amine oxime complexes.
AB  - Up to now, most of the hypoxia markers contain only one nitroimidazole redox
      centre, such as Oxo[[3,3,9,9-tetramethyl-1-(2-nitro-1H-imidazol-1-yl)-4,8
      diazaundecane-2,10-dione dioximato] (3-)-N,N',N",N"']-technetium ((99m)Tc-1,
      BMS181321). Introducing a second nitroimidazole redox centre may enhance the
      hypoxic accumulation of the markers. In the present work, four (99m)Tc-1
      (BMS181321, containing one 2-nitroimidazole) analogues, that is, (99m)Tc-2
      (containing two 2-nitroimidazoles), (99m)Tc-3 (containing one 4-nitroimidazole),
      (99m)Tc-4 (containing two 4-nitroimidazoles) and (99m)Tc-5 (containing both a 2
      nitroimidazole and a 4-nitroimidazole) were synthesized, and the hypoxic
      accumulation was evaluated in vitro using murine sarcoma S180 cells. (99m)Tc-3
      and (99m)Tc-4 displayed no significant anoxic/normoxic differentials, whereas
      (99m)Tc-1 (BMS181321), (99m)Tc-2 and (99m)Tc-5 showed high anoxic cellular
      uptakes. The anoxic uptake of (99m)Tc-2 reached up to 59.0+/-0.9% at 4h, which
      was 2.4 times as that of (99m)Tc-1. (99m)Tc-2 displayed high hypoxic
      accumulation, indicating that introducing a second nitroimidazole redox centre,
      that is, 2-nitroimidazole, affected the hypoxic accumulation. Consequently,
      (99m)Tc-2 may serve as a viable candidate for hypoxia marker. This finding may
      eventually lead to the development of compounds containing multi-redox centres as
      hypoxia markers.

PMID- 22153342
TI  - Synthesis and evaluation of 4-alkoxy-[1'-cyclobutyl-spiro(3,4-dihydrobenzopyran
      2,4'-piperidine)] analogues as histamine-3 receptor antagonists.
AB  - A novel class of 4-alkoxy-[1'-cyclobutyl-spiro(3,4-dihydrobenzopyran-2,4'
      piperidine)] analogues were designed and synthesized as H(3)R antagonists.
      Structure-activity relationship identified sulfone 27 with excellent H(3)R
      affinities in both humans and rats, and acceptable pharmacokinetic properties.
      Further, compound 28 achieved single digit nanomolar H(3)R affinities in both
      species with minimum hERG activity.

PMID- 22153343
TI  - Synthesis and biological evaluation of molecular probes based on the 9
      methylstreptimidone derivative DTCM-glutarimide.
AB  - Molecular probes based on 3-[(dodecylthiocarbonyl)methyl]glutarimide (DTCM
      glutarimide) were synthesized and assessed for inhibitory activity against LPS
      induced NO production. Among the probes examined, several derivatives exhibited
      potential for use in determining the target proteins of DTCM-glutarimide.

PMID- 22153344
TI  - Synthesis and in vitro and in vivo anticancer activity of novel phenylmethylene
      bis-isoxazolo[4,5-b]azepines.
AB  - A series of novel phenylmethylene bis-isoxazolo[4,5-b]azepine derivatives (10)
      have been synthesized from 3-methyl-4-nitro-5-styrylisoxazoles 6. The reaction of
      6 with 3,5-dimethyl-4-nitroisoxazole (7) in piperidine afforded the Michael type
      adducts 8, which on treatment with different substituted chalcones in the
      presence of piperidine gave the Michael adducts 9. Compounds 9 underwent
      reductive cyclization on treatment with SnCl(2)-MeOH to afford the title
      compounds 10. Structure of these compounds was established on the basis of IR,
      (1)H NMR, (13)C NMR and Mass spectral data. The title compounds 10a-j were
      evaluated for in vitro and in vivo anticancer activity. Compound 10j exhibited
      good anticancer activity as that of standard drug Cisplatin.

PMID- 22153345
TI  - Eudesmane-type sesquiterpene lactones inhibit multiple steps in the NF-kappaB
      signaling pathway induced by inflammatory cytokines.
AB  - Inflammatory cytokines, such as interleukin-1alpha (IL-1alpha) and tumor necrosis
      factor-alpha (TNF-alpha), induce the intracellular signaling pathway leading to
      the activation of nuclear factor kappaB (NF-kappaB). A series of eudesmane-type
      sesquiterpene lactones possessing an alpha-methylene gamma-lactone group and/or
      an alpha-bromo ketone group were synthesized and evaluated for their inhibitory
      effects on the NF-kappaB-dependent gene expression and signaling pathway. Our
      present study reveals that eudesmane-type alpha-methylene gamma-lactones and
      alpha-bromo ketones inhibit multiple steps in the NF-kappaB signaling pathway
      induced by IL-1alpha and TNF-alpha.

PMID- 22153347
TI  - Lead optimization of 2-(piperidin-3-yl)-1H-benzimidazoles: identification of 2
      morpholin- and 2-thiomorpholin-2-yl-1H-benzimidazoles as selective and CNS
      penetrating H1-antihistamines for insomnia.
AB  - The structure-activity relationships of 2-(piperidin-3-yl)-1H-benzimidazoles, 2
      morpholine and 2-thiomorpholin-2-yl-1H-benzimidazoles are described. In the lead
      optimization process, the pK(a) and/or logP of benzimidazole analogs were reduced
      either by attachment of polar substituents to the piperidine nitrogen or
      incorporation of heteroatoms into the piperidine heterocycle. Compounds 9a and 9b
      in the morpholine series and 10g in the thiomorpholine series demonstrated
      improved selectivity and CNS profiles compared to lead compound 2 and these are
      potential candidates for evaluation as sedative hypnotics.

PMID- 22153346
TI  - In vitro inhibition of translation initiation by N,N'-diarylureas--potential anti
      cancer agents.
AB  - Symmetrical N,N'-diarylureas: 1,3-bis(3,4-dichlorophenyl)-, 1,3-bis[4-chloro-3
      (trifluoromethyl)phenyl]- and 1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea, were
      identified as potent activators of the eIF2alpha kinase heme regulated inhibitor.
      They reduce the abundance of the eIF2.GTP.tRNA(i)(Met) ternary complex and
      inhibit cancer cell proliferation. An optimization process was undertaken to
      improve their solubility while preserving their biological activity. Non
      symmetrical hybrid ureas were generated by combining one of the hydrophobic
      phenyl moieties present in the symmetrical ureas with the polar 3-hydroxy-tolyl
      moiety. O-alkylation of the later added potentially solubilizing charge bearing
      groups. The new non-symmetrical N,N'-diarylureas were characterized by ternary
      complex reporter gene and cell proliferation assays, demonstrating good
      bioactivities. A representative sample of these compounds potently induced
      phosphorylation of eIF2alpha and expression of CHOP at the protein and mRNA
      levels. These inhibitors of translation initiation may become leads for the
      development of potent, non-toxic, and target specific anti-cancer agents.

PMID- 22153348
TI  - Sarcopenia in the elderly: diagnosis, physiopathology and treatment.
AB  - Sarcopenia, defined as a syndrome rather than as a pathology, is the loss of
      muscle mass and function associated with age. Sarcopenia is an enigma for
      medicine, and despite the numerous publications available in the literature and
      the number of papers currently being published, there is no agreement about its
      definition, and even less about its root causes. One salient aspect that proves
      the lack of consensus is the fact that different working groups are still
      debating about the right name for this syndrome (which is associated with the
      loss of muscle mass and strength in the elderly). In hospitalized patients,
      sarcopenia has been shown to raise the risk of complications such as infections,
      pressure ulcers, loss of autonomy, institutionalization and poor quality of life,
      as well as to increase mortality. The factors that contribute to the development
      of sarcopenia in the elderly are: the state of chronic inflammation, atrophy of
      motoneurons, reduced protein intake (secondary among others to the condition
      defined as geriatric anorexia), and immobility. There is ongoing debate about the
      causes of sarcopenia, but the aspect that generates most interest today is the
      quest to achieve repeatable and clinically useful diagnostic criteria for its
      diagnosis, prevention and treatment. The aim of this narrative review is to
      summarise the abundant information available in the literature and to draw useful
      conclusions.

PMID- 22153349
TI  - Association between depression and bone mineral density in community-dwelling
      older men and women in Korea.
AB  - OBJECTIVES: Previous research suggested a significant correlation between
      depression and osteoporosis, but little is known for the elderly Asian
      population. We investigated an association between depression and bone mineral
      density (BMD) in the Korean elderly. STUDY DESIGN: Cross-sectional data analysis
      of a community-based study, Kangwha Island, South Korea. MAIN OUTCOME MEASURES:
      BMD, measured at the os calcis using a quantitative ultrasound device, was
      expressed as stiffness index and T-score. Depressive symptoms were evaluated by
      the Korean version of Beck Depression Inventory (K-BDI). Depression was defined
      as a K-BDI score of 16 or higher. Participants also completed a questionnaire,
      including demographic factors, metabolic abnormalities, and health-related
      lifestyle factors. RESULTS: A total of 932 local residents (422 men and 510
      women) aged 60-80 years completed the questionnaires and baseline BMD evaluation.
      Men with depression had a significantly lower stiffness index compared to those
      without depression in an age-adjusted (77.2+/-5.2 vs. 86.0+/-1.5, p=0.002) and a
      multivariate-adjusted model (78.5+/-5.2 vs. 85. 9+/-1.5, p=0.007).
      Correspondingly, men with depression had an increased probability of having an
      osteoporosis (T-score<=-2.5) compared to those without depression; the age
      adjusted odds ratio was 2.86 (95% CI, 1.36-6.01) and the multivariate-adjusted
      odds ratio was 2.69 (95% CI, 1.26-5.76). However, no significant association was
      observed in older women. CONCLUSIONS: Depression was significantly associated
      with lower BMD in Korean older men, but not in women.

PMID- 22153350
TI  - Matrix metalloproteinase-28 deletion amplifies inflammatory and extracellular
      matrix responses to cardiac aging.
AB  - To determine if matrix metalloproteinase (MMP)-28 mediates cardiac aging, wild
      type (WT) and MMP-28-/- young (7 +/- 1 months, n = 9 each) and old (20 +/- 2
      months, n = 7 each) female mice were evaluated. MMP-28 expression in the left
      ventricle (LV) increased 42% in old WT mice compared to young controls (p <
      0.05). By Doppler echocardiography, LV function declined at 20 +/- 2 months of
      age for both groups. However, dobutamine stress responses were similar,
      indicating that cardiac reserve was maintained. Plasma proteomic profiling
      revealed that macrophage inflammatory protein (MIP)-1 alpha, MIP-1beta and MMP-9
      plasma levels did not change in WT old mice but were significantly elevated in
      MMP-28-/- old mice (all p < 0.05), suggestive of a higher inflammatory status
      when MMP-28 is deleted. RT2-PCR gene array and immunoblotting analyses
      demonstrated that MIP-1alpha and MMP-9 gene and protein levels in the LV were
      also higher in MMP-28-/- old mice (all p < 0.05). Macrophage numbers in the LV
      increased similarly in WT and MMP-28-/- old mice, compared to respective young
      controls (both p < 0.05). Collagen content was not different among the WT and MMP
      28-/- young and old mice. In conclusion, LV inflammation increases with age, and
      MMP-28 deletion further elevates inflammation and extracellular matrix responses,
      without altering macrophage numbers or collagen content.

PMID- 22153351
TI  - Bacterial plasmid partition machinery: a minimalist approach to survival.
AB  - The accurate segregation or partition of replicated DNA is essential for ensuring
      stable genome transmission. Partition of bacterial plasmids requires only three
      elements: a centromere-like DNA site and two proteins, a partition NTPase, and a
      centromere-binding protein (CBP). Because of this simplicity, partition systems
      have served as tractable model systems to study the fundamental molecular
      mechanisms required for DNA segregation at an atomic level. In the last few
      years, great progress has been made in this endeavor. Surprisingly, these studies
      have revealed that although the basic partition components are functionally
      conserved between three types of plasmid partition systems, these systems employ
      distinct mechanisms of DNA segregation. This review summarizes the molecular
      insights into plasmid segregation that have been achieved through these recent
      structural studies.

PMID- 22153352
TI  - Creation and implementation of an emergency general surgery registry modeled
      after the National Trauma Data Bank.
AB  - BACKGROUND: As emergency general surgery (EGS) evolves, an EGS patient-tracking
      database (EGS registry [EGSR]) similar to the National Trauma Data Bank (NTDB)
      will be essential to study outcomes and improve care. The goal of this study was
      to establish diagnostic ICD-9 codes to define EGS patients. The hypothesis was
      that creating standardized ICD-9-based inclusion criteria would facilitate
      patient identification for an EGSR and aid in its ongoing development. STUDY
      DESIGN: We conducted a retrospective review of EGS admissions over a 9-month
      period to define ICD-9 diagnostic codes of patients admitted to our EGS service.
      Subsequently, prospective data were collected into the EGSR by testing ICD-9
      based inclusion criteria over 1 month. Patient, hospital, and severity scoring
      variables, as well as quality assurance information, were identified. RESULTS: We
      identified 959 admissions to the EGS service over 9 months with 306 ICD-9
      diagnosis codes that define EGS patients; the prospective population of the EGSR
      confirmed feasibility of ICD-9-based inclusion criteria. The EGSR captures 107
      data points and 33 comorbidities per patient over 11 categories, akin to the 10
      NTDB categories. CONCLUSIONS: Following the model of the NTDB, we have
      successfully completed creation and initial implementation of an EGSR by using
      ICD-9-based inclusion criteria. Our comprehensive EGSR creates a prospective data
      collection modality to capture and define EGS patients. A uniform patient
      tracking EGSR, akin to the NTDB, will advance the science of acute care surgery,
      improve EGS patient outcomes, and facilitate multi-institutional collaboration.

PMID- 22153353
TI  - Fast removal of cyanobacterial toxin microcystin-LR by a low-cytotoxic microgel
      Fe(III) complex.
AB  - Eutrophication has become a serious environmental threat throughout the world. In
      particular, the presence of cyanobacteria toxins, especially microcystins (MCs),
      has become a severe problem. Inhibition of Microcystis growth in water resources
      is the most effective way to reduce MCs, but it is a long-term investment. In the
      present study, a microgel-Fe(III) complex was developed for the fast removal of
      MC-LR. The microgel-Fe(III) characteristics and the MC-LR removal dynamics in
      Milli-Q water and natural water were evaluated. The removal efficiency negatively
      correlated to the initial MC-LR concentration and pH value (2.0-11.5), but the
      kinetics was not significantly influenced. The presence of natural organic matter
      (NOM) in water slightly reduced MC-LR removal using microgel-Fe(III). In
      addition, microgel-Fe(III) removed 98.99% of MC-LR in 12 min, while for activated
      carbon, it took 15-24 h to reach equilibrium. Furthermore, methanol was found to
      regenerate the microgel-Fe(III) after MC-LR removal for at least five
      regeneration cycles. Finally, the microgel-Fe(III) material was made into a
      membrane so that MCs could be removed by filtration. Therefore, microgel-Fe(III)
      is an effective technology and has a great potential in removing MC-LR from
      drinking water resources.

PMID- 22153354
TI  - Fast atrazine photodegradation in water by pulsed light technology.
AB  - Pulsed light technology consists of a successive repetition of short duration
      (325MUs) and high power flashes emitted by xenon lamps. These flashlamps radiate
      a broadband emission light (approx. 200-1000 nm) with a considerable amount of
      light in the short-wave UV spectrum. In the present work, this technology was
      tested as a new tool for the degradation of the herbicide atrazine in water. To
      evaluate the presence and evolution with time of this herbicide, as well as the
      formation of derivatives, liquid chromatography-mass spectrometry (electrospray
      ionization) ion trap operating in positive mode was used. The degradation process
      followed first-order kinetics. Fluences about 1.8-2.3 J/cm(2) induced 50%
      reduction of atrazine concentration independently of its initial concentration in
      the range 1-1000 MUg/L. Remaining concentrations of atrazine, below the current
      legal limit for pesticides, were achieved in a short period of time. While
      atrazine was degraded, no chlorinated photoproducts were formed and ten
      dehalogenated derivatives were detected. The molecular structures for some of
      these derivatives could be suggested, being hydroxyatrazine the main photoproduct
      identified. The different formation profiles of photoproducts suggested that the
      degradation pathway may include several successive and competitive steps, with
      subsequent degradation processes taking part from the already formed degradation
      products. According to the degradation efficiency, the short treatment time and
      the lack of chloroderivatives, this new technology could be considered as an
      alternative for water treatment.

PMID- 22153355
TI  - Impact of advanced water conservation features and new copper pipe on rapid
      chloramine decay and microbial regrowth.
AB  - Taste and odor issues occurring in new buildings were attributed to rapid loss of
      chloramine residual, high levels of microbes in the potable water system, and
      high water age due to use of advanced water conservation devices. Laboratory
      experiments confirmed that chloramine could decay rapidly in the presence of new
      copper pipe, providing a possible explanation for the rapid disinfectant loss in
      the new buildings. Higher temperature and lower pH also accelerated the rate of
      chloramine decay in copper pipes. The reaction was slowed by the addition of
      phosphate inhibitor or aluminum, which presumably formed barriers between the
      pipe wall and the chloramine in the bulk water. Additional research is needed to
      better understand how to maintain high quality water in buildings while also
      conserving water.

PMID- 22153356
TI  - Modeling volatile organic sulfur compounds in mesophilic and thermophilic
      anaerobic digestion of methionine.
AB  - Processes involved in volatile organic sulfur compound (VOSC) generation and
      degradation in mesophilic and thermophilic digestion of methionine were
      identified, kinetically studied and a mathematical model was established. MM was
      found to be the only VOSC directly generated from methionine degradation. MM was
      methylated to form DMS and both MM and DMS were subsequently degraded to H2S.
      Mixed-second order kinetics were found to best fit the VOSC generation and
      conversion processes. The kinetic constants (average values) for MM generation
      and methylation and MM and DMS degradation were estimated to be 0.0032, 0.0047,
      0.027, and 0.013 l g(-1) h(-1) respectively at 35  degrees C and 0.0069, 0.0012,
      0.0083, 0.005 l g(-1) h(-1) respectively at 55  degrees C. More rapid MM release
      and slower VOSC decline at thermophilic temperature implied that VOSC could be
      more problematic at thermophilic temperatures as compared to mesophilic
      conditions.

PMID- 22153357
TI  - A novel algorithm combining support vector machine with the discrete wavelet
      transform for the prediction of protein subcellular localization.
AB  - Knowing the subcellular localization of proteins within the cell is an important
      step in elucidating its role in biological processes, its function and its
      potential as a drug target for disease diagnosis. As the number of complete
      genomes rapidly increases, accurate and efficient methods that automatically
      predict the subcellular localizations become more urgent. In the current paper,
      we developed a novel method that coupled the discrete wavelet transform with
      support vector machine based on the amino acid polarity to predict the
      subcellular localizations of prokaryotic and eukaryotic proteins. The results
      obtained by the jackknife test were quite promising, and indicated that the
      proposed method remarkably improved the prediction accuracy of subcellular
      locations, and could be as an effective and promising high-throughput method in
      the subcellular localization research.

PMID- 22153358
TI  - Corneal biomechanical properties and intraocular pressure measurement in Marfan
      patients.
AB  - PURPOSE: To compare the biomechanical properties of the cornea and intraocular
      pressure (IOP) between patients with Marfan syndrome and age-matched controls.
      SETTING: Departments of Ophthalmology and Genetics, Bakirkoy Maternity and
      Children Diseases Hospital, and Beyoglu Eye Education and Research Hospital,
      Istanbul, Turkey. DESIGN: Cross-sectional study. METHODS: This study comprised
      patients with Marfan syndrome (study group) and healthy individuals (control
      group). The study group was subdivided into patients with ectopia lentis and
      patients without ectopia lentis. In the right eye of each patient, the corneal
      hysteresis (CH), corneal resistance factor (CRF), Goldman-correlated IOP, and
      corneal-compensated IOP were recorded. RESULTS: Overall, the mean CH, CRF,
      Goldman-correlated IOP, and corneal-compensated IOP were not significantly
      different between the study group and the control group. The mean CH was 9.9 mm
      Hg +/- 1.2 (SD) in study eyes with ectopia lentis and 11.2 +/- 1.5 mm Hg in study
      eyes without ectopia lentis (P=.016); the mean CRF was 8.2 +/- 1.8 mm Hg and 11.3
      +/- 1.9 mm Hg, respectively (P<.001). The mean Goldman-correlated IOP was 11.7 +/
      2.7 mm Hg in study eyes with ectopia lentis and 16.2 +/- 4.3 in study eyes
      without ectopia lentis (P=.003); the mean corneal-compensated IOP was 13.5 +/-
      4.1 mm Hg and 15.6 +/- 3.8 mm Hg, respectively (P=.07). CONCLUSION: The CH, CRF,
      and Goldman-correlated IOP were significantly lower in the Marfan syndrome eyes
      with ectopia lentis than in the Marfan syndrome eyes without ectopia lentis.

PMID- 22153359
TI  - A multi-gene analysis of diversity of Bartonella detected in fleas from Algeria.
AB  - We report the molecular detection of several Bartonella species in 44 (21.5%) of
      204 fleas from Algeria collected from 26 rodents and 7 hedgehogs. Bartonella
      elizabethae and B. clarridgeiae were detected in the fleas collected on
      hedgehogs. Bartonella tribocorum and B. elizabethae were detected in fleas
      collected from rats and mice, and sequences similar to an unnamed Bartonella sp.
      detected in rodents from China were detected in rats as well as a genotype of
      Bartonella closely related to Bartonella rochalimae detected in fleas collected
      on brown rats (Rattus norvegicus).

PMID- 22153360
TI  - Bartonella and Rickettsia in arthropods from the Lao PDR and from Borneo,
      Malaysia.
AB  - Rickettsioses and bartonelloses are arthropod-borne diseases of mammals with
      widespread geographical distributions. Yet their occurrence in specific regions,
      their association with different vectors and hosts and the infection rate of
      arthropod-vectors with these agents remain poorly studied in South-east Asia. We
      conducted entomological field surveys in the Lao PDR (Laos) and Borneo, Malaysia
      by surveying fleas, ticks, and lice from domestic dogs and collected additional
      samples from domestic cows and pigs in Laos. Rickettsia felis was detected by
      real-time PCR with similar overall flea infection rate in Laos (76.6%, 69/90) and
      Borneo (74.4%, 268/360). Both of the encountered flea vectors Ctenocephalides
      orientis and Ctenocephalides felis felis were infected with R. felis. The degrees
      of similarity of partial gltA and ompA genes with recognized species indicate the
      rickettsia detected in two Boophilus spp. ticks collected from a cow in Laos may
      be a new species. Isolation and further characterization will be necessary to
      specify it as a new species. Bartonella clarridgeiae was detected in 3/90 (3.3%)
      and 2/360 (0.6%) of examined fleas from Laos and Borneo, respectively. Two fleas
      collected in Laos and one flea collected in Borneo were co-infected with both R.
      felis and B. clarridgeiae. Further investigations are needed in order to isolate
      these agents and to determine their epidemiology and aetiological role in unknown
      fever in patients from these areas.

PMID- 22153361
TI  - Effect of biological therapy on levels of atheroprotective antibodies against
      phosphorylcholine and apolipoproteins in rheumatoid arthritis - a one year study.
AB  - OBJECTIVES: To examine how treatment of rheumatoid arthritis (RA) with anti
      tumour necrosis factor alpha antagonists (anti-TNF) and B-cell targeting
      rituximab influences novel markers of atherosclerosis and inflammation, such as
      atheroprotective natural IgM antibodies against phosphorylcholine (anti-PC),
      oxidised low-density lipoprotein (oxLDL) and apolipoproteins. METHODS: In a
      prospective study 215 patients with RA were enrolled of whom 85.6% were
      seropositive, aged 57.9 +/- 12.4 years, with mean disease duration 8.5 (5-15)
      years. 162 patients were treated with anti-TNF and 53 with rituximab for one
      year. The patients were assessed and blood sampled at 0, 3, 6 and 12 months. IgM
      anti-PC and oxLDL were determined by ELISA and apolipoproteins by
      immunoturbidimetry. RESULTS: IgM anti-PC increased by 26% during anti-TNF
      treatment, p<0.001, while decreased by 14% on rituximab, p=0.023, after 12 months
      of treatment. Patients in remission after 12 months, DAS28<2.6, had higher
      baseline anti-PC levels compared with those not in remission in both anti-TNF,
      p=0.007, and rituximab-treated subjects, p=0.041. In both treatment groups,
      levels of oxLDL increased temporarily at three months but apoA1 improved
      throughout the study. This effect was inversely correlated with changes in
      disease activity. The apoB and apoB/apoA1-ratio remained stable throughout the
      whole study period. CONCLUSIONS: Anti-TNF treatment demonstrated a favourable
      long-term effect on anti-PC levels. Low levels of IgM anti-PC may identify immune
      deficient state and predict inferior therapy response. Biological therapies
      increased the level of the anti-atherogenic lipid apoA1. The impact of these
      effects on future CVD events deserves further studies.

PMID- 22153362
TI  - Sex and modulatory menstrual cycle effects on sleep related memory consolidation.
AB  - The benefit of sleep in general for memory consolidation is well known. The
      relevance of sleep characteristics and the influence of hormones are not well
      studied. We explored the effects of a nap on memory consolidation of motor
      (finger-tapping-task) and verbal (associated-word-pairs) tasks in following
      settings: A: young, healthy males and females during early-follicular phase
      (n=40) and B: females during mid-luteal and early-follicular phase in the
      menstrual cycle (n=15). We found a sex and in women a menstrual cycle effect on
      memory performance following a nap. Men performed significantly better after a
      nap and women did so only in the mid-luteal phase of their menstrual cycle. Only
      the men and the women in their mid-luteal phase experienced a significant
      increase in spindle activity after learning. Furthermore, in women estrogen
      correlated significantly with the offline change in declarative learning and
      progesterone with motor learning. The ratio of the 2nd and 4th digit, which has
      been associated to fetal sex hormones and cognitive sex differences,
      significantly predicted the average performance of the female subjects in the
      learning tasks. Our results demonstrate that sleep-related memory consolidation
      has a higher complexity and more influencing factors than previously assumed.
      There is a sex and menstrual cycle effect, which seems to be mediated by female
      hormones and sleep spindles. Further, contrary to previous reports, consolidation
      of a simple motor task can be induced by a 45 min NREM sleep nap, thus not
      dependent on REM sleep.

PMID- 22153363
TI  - Crashpilot underachieves due to acetylation at the nerve terminal.
AB  - Protein acetylation is mostly known for its role in chromatin remodeling. In this
      issue, Miskiewicz and colleagues reveal a novel function of acetylation at the
      nerve terminal, where it regulates T bars and the number of associated synaptic
      vesicles to ultimately control the efficacy of synaptic transmission.

PMID- 22153364
TI  - Illuminating synapse-specific homeostatic plasticity.
AB  - Homeostatic plasticity can globally scale the strength of all synapses on a
      neuron, but whether a similar bidirectional homeostatic scaling can also operate
      independently at individual synapses was unknown until now. Here, Man and
      colleagues demonstrate that single synapses show an input-specific homeostatic
      downregulation of synaptic efficacy in response to increased activity.

PMID- 22153365
TI  - Mechanisms of selective attention: response enhancement, noise reduction, and
      efficient pooling of sensory responses.
AB  - In this issue of Neuron, Pestilli and coworkers provide evidence that response
      gain and noise reduction are insufficient to account for attention-induced
      changes in perception. Instead, selection may critically depend on the biased
      pooling of sensory signals during decision making.

PMID- 22153366
TI  - Can cognitive training improve episodic memory?
AB  - Neuroscience-inspired approaches to train cognitive abilities are bringing about
      a paradigm shift in the way scientists view the treatment of memory dysfunction,
      but it can be challenging to prove whether such approaches have significant
      effects.

PMID- 22153367
TI  - Inferring mental states from neuroimaging data: from reverse inference to large
      scale decoding.
AB  - A common goal of neuroimaging research is to use imaging data to identify the
      mental processes that are engaged when a subject performs a mental task. The use
      of reasoning from activation to mental functions, known as "reverse inference,"
      has been previously criticized on the basis that it does not take into account
      how selectively the area is activated by the mental process in question. In this
      Perspective, I outline the critique of informal reverse inference and describe a
      number of new developments that provide the ability to more formally test the
      predictive power of neuroimaging data.

PMID- 22153368
TI  - Evolution of insect olfaction.
AB  - Neuroethology utilizes a wide range of multidisciplinary approaches to decipher
      neural correlates of natural behaviors associated with an animal's ecological
      niche. By placing emphasis on comparative analyses of adaptive and evolutionary
      trends across species, a neuroethological perspective is uniquely suited to
      uncovering general organizational and biological principles that shape the
      function and anatomy of the nervous system. In this review, we focus on the
      application of neuroethological principles in the study of insect olfaction and
      discuss how ecological environment and other selective pressures influence the
      development of insect olfactory neurobiology, not only informing our
      understanding of olfactory evolution but also providing broader insights into
      sensory processing.

PMID- 22153369
TI  - In search of a consensus model of the resting state of a voltage-sensing domain.
AB  - Voltage-sensing domains (VSDs) undergo conformational changes in response to the
      membrane potential and are the critical structural modules responsible for the
      activation of voltage-gated channels. Structural information about the key
      conformational states underlying voltage activation is currently incomplete.
      Through the use of experimentally determined residue-residue interactions as
      structural constraints, we determine and refine a model of the Kv channel VSD in
      the resting conformation. The resulting structural model is in broad agreement
      with results that originate from various labs using different techniques,
      indicating the emergence of a consensus for the structural basis of voltage
      sensing.

PMID- 22153371
TI  - Secreted semaphorins from degenerating larval ORN axons direct adult projection
      neuron dendrite targeting.
AB  - During assembly of the Drosophila olfactory circuit, projection neuron (PN)
      dendrites prepattern the developing antennal lobe before the arrival of axons
      from their presynaptic partners, the adult olfactory receptor neurons (ORNs). We
      previously found that levels of transmembrane Semaphorin-1a, which acts as a
      receptor, instruct PN dendrite targeting along the dorsolateral-ventromedial
      axis. Here we show that two secreted semaphorins, Sema-2a and Sema-2b, provide
      spatial cues for PN dendrite targeting. Sema-2a and Sema-2b proteins are
      distributed in gradients opposing the Sema-1a protein gradient, and Sema-1a binds
      to Sema-2a-expressing cells. In Sema-2a and Sema-2b double mutants, PN dendrites
      that normally target dorsolaterally in the antennal lobe mistarget
      ventromedially, phenocopying cell-autonomous Sema-1a removal from these PNs. Cell
      ablation, cell-specific knockdown, and rescue experiments indicate that secreted
      semaphorins from degenerating larval ORN axons direct dendrite targeting. Thus, a
      degenerating brain structure instructs the wiring of a developing circuit through
      the repulsive action of secreted semaphorins.

PMID- 22153370
TI  - Recombinase-driver rat lines: tools, techniques, and optogenetic application to
      dopamine-mediated reinforcement.
AB  - Currently there is no general approach for achieving specific optogenetic control
      of genetically defined cell types in rats, which provide a powerful experimental
      system for numerous established neurophysiological and behavioral paradigms. To
      overcome this challenge we have generated genetically restricted recombinase
      driver rat lines suitable for driving gene expression in specific cell types,
      expressing Cre recombinase under the control of large genomic regulatory regions
      (200-300 kb). Multiple tyrosine hydroxylase (Th)::Cre and choline
      acetyltransferase (Chat)::Cre lines were produced that exhibited specific opsin
      expression in targeted cell types. We additionally developed methods for
      utilizing optogenetic tools in freely moving rats and leveraged these
      technologies to clarify the causal relationship between dopamine (DA) neuron
      firing and positive reinforcement, observing that optical stimulation of DA
      neurons in the ventral tegmental area (VTA) of Th::Cre rats is sufficient to
      support vigorous intracranial self-stimulation (ICSS). These studies complement
      existing targeting approaches by extending the generalizability of optogenetics
      to traditionally non-genetically-tractable but vital animal models.

PMID- 22153372
TI  - p63 regulates olfactory stem cell self-renewal and differentiation.
AB  - The olfactory epithelium is a sensory neuroepithelium that supports adult
      neurogenesis and tissue regeneration following injury, making it an excellent
      model for investigating neural stem cell regulation in vivo. Previous studies
      have identified the horizontal basal cell (HBC) as the neural stem cell of the
      postnatal olfactory epithelium. However, the molecules and pathways regulating
      HBC self-renewal and differentiation are unknown. In the present study, we
      demonstrate that the transcription factor p63, a member of the p53 tumor
      suppressor gene family known to regulate stem cell dynamics in other epithelia,
      is highly enriched in HBCs. We show that p63 is required cell autonomously for
      olfactory stem cell renewal and further demonstrate that p63 functions to repress
      HBC differentiation. These results provide critical insight into the genetic
      regulation of the olfactory stem cell in vivo and more generally provide an
      entree toward understanding the coordination of stem cell self-renewal and
      differentiation.

PMID- 22153374
TI  - ELP3 controls active zone morphology by acetylating the ELKS family member
      Bruchpilot.
AB  - Elongator protein 3 (ELP3) acetylates histones in the nucleus but also plays a
      role in the cytoplasm. Here, we report that in Drosophila neurons, ELP3 is
      necessary and sufficient to acetylate the ELKS family member Bruchpilot, an
      integral component of the presynaptic density where neurotransmitters are
      released. We find that in elp3 mutants, presynaptic densities assemble normally,
      but they show morphological defects such that their cytoplasmic extensions cover
      a larger area, resulting in increased vesicle tethering as well as a more
      proficient neurotransmitter release. We propose a model where ELP3-dependent
      acetylation of Bruchpilot at synapses regulates the structure of individual
      presynaptic densities and neurotransmitter release efficiency.

PMID- 22153373
TI  - Glial-derived prodegenerative signaling in the Drosophila neuromuscular system.
AB  - We provide evidence for a prodegenerative, glial-derived signaling framework in
      the Drosophila neuromuscular system that includes caspase and mitochondria
      dependent signaling. We demonstrate that Drosophila TNF-alpha (eiger) is
      expressed in a subset of peripheral glia, and the TNF-alpha receptor (TNFR),
      Wengen, is expressed in motoneurons. NMJ degeneration caused by disruption of the
      spectrin/ankyrin skeleton is suppressed by an eiger mutation or by eiger
      knockdown within a subset of peripheral glia. Loss of wengen in motoneurons
      causes a similar suppression providing evidence for glial-derived prodegenerative
      TNF-alpha signaling. Neither JNK nor NFkappabeta is required for prodegenerative
      signaling. However, we provide evidence for the involvement of both an initiator
      and effector caspase, Dronc and Dcp-1, and mitochondrial-dependent signaling.
      Mutations that deplete the axon and nerve terminal of mitochondria suppress
      degeneration as do mutations in Drosophila Bcl-2 (debcl), a mitochondria
      associated protein, and Apaf-1 (dark), which links mitochondrial signaling with
      caspase activity in other systems.

PMID- 22153375
TI  - A critical role for GluN2B-containing NMDA receptors in cortical development and
      function.
AB  - The subunit composition of N-methyl D-aspartate receptors (NMDARs) is tightly
      regulated during cortical development. NMDARs are initially dominated by GluN2B
      (NR2B), whereas GluN2A (NR2A) incorporation increases after birth. The function
      of GluN2B-containing NMDARs during development, however, is incompletely
      understood. We generated a mouse in which we genetically replaced GluN2B with
      GluN2A (2B->2A). Although this manipulation restored NMDAR-mediated currents at
      glutamatergic synapses, it did not rescue GluN2B loss of function. Protein
      translation-dependent homeostatic synaptic plasticity is occluded in the absence
      of GluN2B, and AMPA receptor contribution is enriched at excitatory cortical
      synapses. Our experiments indicate that specificity of GluN2B-mediated signaling
      is due to its unique interaction with the protein effector alpha calcium
      calmodulin kinase II and the regulation of the mTOR pathway. Homozygous 2B->2A
      mice exhibited high rates of lethality, suppressed feeding, and depressed social
      exploratory behavior. These experiments indicate that GluN2B-containing NMDARs
      activate unique cellular processes that cannot be rescued by replacement with
      GluN2A.

PMID- 22153376
TI  - Homeostatic regulation of AMPA receptor trafficking and degradation by light
      controlled single-synaptic activation.
AB  - During homeostatic adjustment in response to alterations in neuronal activity,
      synaptic expression of AMPA receptors (AMPARs) is globally tuned up or down so
      that the neuronal activity is restored to a physiological range. Given that a
      central neuron receives multiple presynaptic inputs, whether and how AMPAR
      synaptic expression is homeostatically regulated at individual synapses remain
      unclear. In cultured hippocampal neurons we report that when activity of an
      individual presynaptic terminal is selectively elevated by light-controlled
      excitation, AMPAR abundance at the excited synapses is selectively downregulated
      in an NMDAR-dependent manner. The reduction in surface AMPARs is accompanied by
      enhanced receptor endocytosis and dependent on proteasomal activity. Synaptic
      activation also leads to a site-specific increase in the ubiquitin ligase Nedd4
      and polyubiquitination levels, consistent with AMPAR ubiquitination and
      degradation in the spine. These results indicate that AMPAR accumulation at
      individual synapses is subject to autonomous homeostatic regulation in response
      to synaptic activity.

PMID- 22153377
TI  - Parallel regulation of feedforward inhibition and excitation during whisker map
      plasticity.
AB  - Sensory experience drives robust plasticity of sensory maps in cerebral cortex,
      but the role of inhibitory circuits in this process is not fully understood. We
      show that classical deprivation-induced whisker map plasticity in layer 2/3
      (L2/3) of rat somatosensory (S1) cortex involves robust weakening of L4-L2/3
      feedforward inhibition. This weakening was caused by reduced L4 excitation onto
      L2/3 fast-spiking (FS) interneurons, which mediate sensitive feedforward
      inhibition and was partially offset by strengthening of unitary FS to L2/3
      pyramidal cell synapses. Weakening of feedforward inhibition paralleled the known
      weakening of feedforward excitation. As a result, mean excitation-inhibition
      balance and timing onto L2/3 pyramidal cells were preserved. Thus, reduced
      feedforward inhibition is a covert compensatory process that can maintain
      excitatory-inhibitory balance during classical deprivation-induced Hebbian map
      plasticity.

PMID- 22153378
TI  - Attentional enhancement via selection and pooling of early sensory responses in
      human visual cortex.
AB  - The computational processes by which attention improves behavioral performance
      were characterized by measuring visual cortical activity with functional magnetic
      resonance imaging as humans performed a contrast-discrimination task with focal
      and distributed attention. Focal attention yielded robust improvements in
      behavioral performance accompanied by increases in cortical responses.
      Quantitative analysis revealed that if performance were limited only by the
      sensitivity of the measured sensory signals, the improvements in behavioral
      performance would have corresponded to an unrealistically large reduction in
      response variability. Instead, behavioral performance was well characterized by a
      pooling and selection process for which the largest sensory responses, those most
      strongly modulated by attention, dominated the perceptual decision. This
      characterization predicts that high-contrast distracters that evoke large
      responses should negatively impact behavioral performance. We tested and
      confirmed this prediction. We conclude that attention enhanced behavioral
      performance predominantly by enabling efficient selection of the behaviorally
      relevant sensory signals.

PMID- 22153380
TI  - Modeling the spatial reach of the LFP.
AB  - The local field potential (LFP) reflects activity of many neurons in the vicinity
      of the recording electrode and is therefore useful for studying local network
      dynamics. Much of the nature of the LFP is, however, still unknown. There are,
      for instance, contradicting reports on the spatial extent of the region
      generating the LFP. Here, we use a detailed biophysical modeling approach to
      investigate the size of the contributing region by simulating the LFP from a
      large number of neurons around the electrode. We find that the size of the
      generating region depends on the neuron morphology, the synapse distribution, and
      the correlation in synaptic activity. For uncorrelated activity, the LFP
      represents cells in a small region (within a radius of a few hundred
      micrometers). If the LFP contributions from different cells are correlated, the
      size of the generating region is determined by the spatial extent of the
      correlated activity.

PMID- 22153379
TI  - How local is the local field potential?
AB  - Local field potentials (LFPs) are of growing importance in neurophysiological
      investigations. LFPs supplement action potential recordings by indexing activity
      relevant to EEG, magnetoencephalographic, and hemodynamic (fMRI) signals. Recent
      reports suggest that LFPs reflect activity within very small domains of several
      hundred micrometers. We examined this conclusion by comparing LFP, current source
      density (CSD), and multiunit activity (MUA) signals in macaque auditory cortex.
      Estimated by frequency tuning bandwidths, these signals' "listening areas" differ
      systematically with an order of MUA < CSD < LFP. Computational analyses confirm
      that observed LFPs receive local contributions. Direct measurements indicate
      passive spread of LFPs to sites more than a centimeter from their origins. These
      findings appear to be independent of the frequency content of the LFP. Our
      results challenge the idea that LFP recordings typically integrate over extremely
      circumscribed local domains. Rather, LFPs appear as a mixture of local potentials
      with "volume conducted" potentials from distant sites.

PMID- 22153381
TI  - Patterns of coordinated anatomical change in human cortical development: a
      longitudinal neuroimaging study of maturational coupling.
AB  - Understanding of human structural brain development has rapidly advanced in
      recent years, but remains fundamentally "localizational" in nature. Here, we use
      376 longitudinally acquired structural brain scans from 108 typically developing
      adolescents to conduct the first study of coordinated anatomical change within
      the developing cortex. Correlation in rates of anatomical change was regionally
      heterogeneous, with fronto-temporal association cortices showing the strongest
      and most widespread maturational coupling with other cortical areas, and lower
      order sensory cortices showing the least. Canonical cortical systems with rich
      structural and functional interconnectivity showed significantly elevated
      maturational coupling. Evidence for sexually dimorphic maturational coupling was
      found within a frontopolar-centered prefrontal system involved in complex
      decision-making. By providing the first link between cortical connectivity and
      the coordination of cortical development, we reveal a hitherto unseen property of
      healthy brain maturation, which may represent a target for neurodevelopmental
      disease processes, and a substrate for sexually dimorphic behavior in
      adolescence.

PMID- 22153383
TI  - Body fat percentage as a risk factor for atherosclerosis but not for inflammation
      for hemodialysis patients: differences between genders.
AB  - INTRODUCTION: Atherosclerosis (AS) and malnutrition are 2 major causes of
      morbidity and mortality in hemodialysis (HD) patients. A high body fat percentage
      (BFP) may be paradoxically associated with improved survival in chronic HD
      patients. We aimed to establish BFP profile of the HD patients by using
      bioimpedance analysis, body mass index (BMI), and waist/hip ratio (WHR) to find
      out their association with inflammation and AS. METHODS: In total, 125 HD
      patients (64 male, 51% mean age of 49.7 +/- 12.3 years) were included in the
      study. Malnutrition-inflammation score (MIS) has been used and supported with
      biochemical parameters: C-reactive protein, serum iron, total iron binding
      capacity, ferritin, complete blood count, serum albumin, total cholesterol, low-
      and high-density lipoproteins, and triglyceride. The patients were divided into 3
      groups according to their BFP that were defined by bioimpedance analysis. We also
      compared these groups according to BMI percentiles. Independent variables
      affecting BMI and MIS were identified by logistic regression analysis. RESULTS:
      AS was correlated with high BFP for our female HD patients, but not for the
      males. BFP, BMI, and WHR were significantly higher for females. Older age (P =
      .02), BMI (P < .01), WHR (P < .01), total leukocyte count (P = .02), serum iron
      (P < .01), and total iron-binding capacity (P = .02) were found significantly
      correlated with higher BFP for female HD patients, whereas only BMI (P < .01) and
      serum creatinine levels (P = .04) were significant for male patients. In logistic
      regression analysis, independent factors affecting cardiovascular disease (CVD)
      were gender, BFP, MIS, and lymphocyte/leukocyte ratio. Independent factors
      affecting MIS were gender, BFP, CVD, serum albumin level, and serum C-reactive
      protein. CONCLUSION: BFP and male gender may be contributing factors for CVD;
      however, female HD patients with high BFP had higher risk of CVD than male
      counterparts. Further studies are needed to evaluate the pathophysiology of this
      discrepancy between genders.

PMID- 22153384
TI  - A serial MRI study in a patient with progressive supranuclear palsy with
      cerebellar ataxia.

PMID- 22153385
TI  - The survival of E. coli O157:H7, S. Typhimurium and L. monocytogenes in black
      carrot (Daucus carota) juice.
AB  - In this study the survival and growth patterns of Escherichia coli O157:H7,
      Salmonella Typhimurium and Listeria monocytogenes in various concentrations of
      black carrot juice were investigated during incubation period at 4  degrees C and
      37  degrees C for 7 days. Several parameters, such as juice concentration (%),
      pH, incubation temperature ( degrees C) and time (days) were found effective on
      the survival of pathogens tested. Although L. monocytogenes has been found to be
      the less resistant microorganism to the variable conditions, there were only ca.
      1 and 2 log reductions in the number of the cells in the juice samples incubated
      at 4  degrees C for 2 and 7 days, respectively. Incubating at low temperature (4 
      degrees C) enhanced the survival of test microorganisms.

PMID- 22153382
TI  - Cognitive dysfunction and depression in adult kidney transplant recipients:
      baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT).
AB  - OBJECTIVE: Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk
      factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive
      impairment, and depression are all common in individuals with kidney disease,
      including kidney transplant recipients. Accordingly, we assessed the prevalence
      of cognitive impairment and depressive symptoms in transplant recipients and
      their association with kidney function, plasma total homocysteine, and B-vitamin
      concentrations. SETTING: Cross-sectional analysis of baseline data from the Folic
      Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) Ancillary
      Cognitive Trial (FACT), which included 183 participants in FAVORIT who underwent
      detailed neuropsychological assessment before the study intervention. RESULTS:
      The mean age was 54.0 +/- 9.5 years (range: 7 to 386 months). Men comprised 55.2%
      of the cohort, and the mean time between the current transplant and cognitive
      testing was 7.0 +/- 5.8 years. Twenty-four percent of participants reported
      neurological or psychiatric complaints, and 30% exhibited symptoms of mild to
      severe depression. Testing revealed evidence of significant and selective
      deficits in this population: 33% performed more than 1 standard deviation (SD)
      below normed means on a memory test, 58% fell lower than 1 SD below the norms on
      a test of attention and mental processing speed, and 33% to 42% fell lower than 1
      SD below the norms on several tests of executive function. Lower estimated
      glomerular filtration rate and lower folate were associated with poorer
      performance on tests of memory and executive function. CONCLUSIONS: These
      observations confirm previous reports of mood and cognitive impairments in adult
      kidney transplant recipients. Further research is needed to determine the benefit
      of B-vitamin supplementation and other interventions in this patient population.

PMID- 22153386
TI  - The assessment of drug calculation skills--time to rethink the whole process.

PMID- 22153387
TI  - High-flow oxygen therapy: pressure analysis in a pediatric airway model.
AB  - BACKGROUND: The mechanism of high-flow oxygen therapy and the pressures reached
      in the airway have not been defined. We hypothesized that the flow would generate
      a low continuous positive pressure, and that elevated flow rates in this model
      could produce moderate pressures. The objective  of this study was to analyze the
      pressure generated by a high-flow oxygen therapy system in an experimental model
      of the pediatric airway. METHODS: An experimental in vitro study was performed. A
      high-flow oxygen therapy system was connected to 3 types of interface (nasal
      cannulae, nasal mask,  and oronasal mask) and applied to 2 types of pediatric
      manikin (infant and neonatal). The pressures generated in the circuit, in the
      airway, and in the pharynx were measured at different flow rates (5, 10, 15, and
      20 L/min). The experiment was conducted with and without a leak (mouth sealed 
      and unsealed). Linear regression analyses were performed for each set of
      measurements. RESULTS: The pressures generated with the different interfaces were
      very similar. The maximum pressure recorded was 4 cm H(2)O with a flow of 20
      L/min via nasal cannulae or nasal mask. When the  mouth of the manikin was held
      open, the pressures reached in the airway and pharynxes were undetectable. Linear
      regression analyses showed a similar linear relationship between flow and
      pressures measured in the pharynx (pressure = -0.375 + 0.138 * flow) and in the
      airway (pressure  = -0.375 + 0.158 * flow) with the closed mouth condition.
      CONCLUSIONS: According to our hypothesis, high-flow oxygen therapy systems
      produced a low-level CPAP in an experimental pediatric model, even with the use
      of very high flow rates. Linear regression analyses showed similar  linear
      relationships between flow and pressures measured in the pharynx and in the
      airway. This finding suggests that, at least in part, the effects may be due to
      other mechanisms.

PMID- 22153389
TI  - Anesthetic neurotoxicity in babies.

PMID- 22153388
TI  - Atorvastatin reduces vascular endothelial growth factor (VEGF) expression in
      human non-small cell lung carcinomas (NSCLCs) via inhibition of reactive oxygen
      species (ROS) production.
AB  - The high metastatic potential of non-small cell lung cancers (NSCLCs) is closely
      correlated with the elevated expression of vascular endothelial growth factor
      (VEGF) and resultant tumor angiogenesis. However, no effective strategies against
      VEGF expression have been available in NSCLCs therapy. This study demonstrated
      that elevated reactive oxygen species (ROS) levels derived from both mitochondria
      and NADPH oxidase were required for VEGF expression in NSCLC cells. Atorvastatin
      administration could significantly inhibit VEGF expression both in vitro and in
      vivo via inhibition of ROS production. Atorvastatin inhibited ROS generation
      partly through suppression of Rac1/NADPH oxidase activity. Specifically,
      atorvastatin could upregulate the activity of glutathione peroxidase (GPx) and
      catalase, which are responsible for elimination of hydrogen peroxide (H(2)O(2))
      in the mitochondria and peroxisomes, respectively. Thus, inhibition of ROS
      production by concomitant suppression of Rac1/NADPH oxidase activity and
      upregulation of the activity of GPx and catalase contributes critically to
      atorvastatin-reduced VEGF expression in NSCLCs. Atorvastatin may be a potential
      alternative against VEGF expression and angiogenesis in NSCLCs therapy.

PMID- 22153390
TI  - Intermittent exotropia: when to observe and when to treat.

PMID- 22153391
TI  - An integrated data systems approach to amblyopia prevention.

PMID- 22153392
TI  - When will my child go blind? Prognosis versus uncertainty and fear-a conceptual
      analysis.

PMID- 22153393
TI  - Dose-effect relationship of medial rectus muscle advancement for consecutive
      exotropia.
AB  - PURPOSE: To evaluate the dose-effect relationship for medial rectus muscle
      advancement in patients with consecutive exotropia. METHODS: Pre- and
      postoperative deviations 1 day and 6 months after surgery were measured by linear
      strabismometric method. The change in deviation (difference between preoperative
      and postoperative deviation at 6 months) was correlated to the surgical dose
      (dose-effect relationship) and the preoperative distance deviation by multiple
      regression analysis. Multivariate regression analysis was performed with three
      and two independent variables (preoperative distance deviation, millimeters of
      advancement, intraoperative muscle stretch test), with change in deviation as a
      dependent variable. RESULTS: Twenty-four patients (mean age, 33 years; range, 18
      60 years) were included. The mean preoperative deviation was 32(?), the mean
      postoperative deviation was 0(?) at day 1, and 9(?) 6 months after surgery. The
      mean dose-effect relationship was 5(?)/mm at day 1 and 4(?)/mm 6 months after
      surgery. Mean exodrift 6 months after surgery was 9(?). The univariate model was
      statistically significant for each variable (P < 0.05). The multivariate model
      was statistically significant for preoperative distance deviation and millimeters
      of advancement (P < 0.05) but not for intraoperative muscle stretch test (P =
      0.1519). CONCLUSIONS: The dose-effect relationship at 6 months after advancement
      of the medial rectus muscle for consecutive exotropia could be a useful guide for
      planning surgical correction, even considering the expected exodrift.

PMID- 22153394
TI  - Postoperative outcomes of patients initially overcorrected for intermittent
      exotropia.
AB  - BACKGROUND: Esotropic overcorrection on postoperative day 1 after surgery for
      intermittent exotropia is generally thought to increase the likelihood of long
      term satisfactory alignment; however, it is unclear why some patients who are
      initially overcorrected demonstrate recurrent intermittent exotropia whereas
      others maintain esotropic to orthotropic alignment. METHODS: The records of all
      patients who underwent primary surgical correction of intermittent exotropia were
      reviewed; those with any degree of esotropia on postoperative day 1 were
      included. The status at the last visit was categorized as orthotropic to
      <8(Delta) exotropia or having recurrent exotropia >8(Delta), monofixational
      esotropia <10(Delta), or esotropia >10(Delta). RESULTS: A total of 63 patients
      met the inclusion criteria. The mean postoperative day 1 alignment was 6(Delta)
      +/- 3(Delta) esotropia at distance and 5(Delta) +/- 3(Delta) esotropia at near.
      At the last visit, 31 (49%) were orthotropic to <8(Delta) exotropia, 26 (41%) had
      recurrence of exotropia >8(Delta), and 6 (10%) had monofixational esotropia
      <10(Delta). There was no significant difference between outcome groups in onset
      age, age at surgery, stereopsis, deviation (preoperatively or on postoperative
      day 1), or follow-up length. Risk factor analysis revealed no association between
      exotropia type, surgical approach, or postoperative day 1 alignment and risk of
      recurrent intermittent exotropia or monofixational esotropia, although there was
      a trend toward recurrent intermittent exotropia in those least overcorrected.
      CONCLUSIONS: Recommended overcorrection on postoperative day 1 for intermittent
      exotropia can result in esotropia, intermittent exotropia, or orthotropia. The
      results of overcorrection for exotropia are variable and unpredictable. We were
      unable to determine associations with the recurrence of exotropia or secondary
      esotropia.

PMID- 22153395
TI  - Anchored versus conventional hang-back bilateral lateral rectus muscle recession
      for exotropia.
AB  - PURPOSE: To compare the results of conventional hang-back and anchored hang-back
      technique for bilateral lateral rectus muscle recessions in patients with
      exotropia. METHODS: In a prospective, randomized clinical study, 60 patients
      underwent lateral rectus muscle recession by either conventional hang-back or
      anchored hang-back technique. Patients were then followed for 6 months;
      postoperative deviation and complications were compared. Surgery was considered
      successful if the postoperative deviation was within 10(Delta) of orthophoria.
      RESULTS: The mean age of patients was 14.2 +/- 10.3 years (median, 12 years) in
      the conventional hang-back group and 11.5 +/- 9.3 years (median, 8 years) in
      anchored group (P = 0.85). The mean preoperative deviation at distance and near
      between the 2 groups was not statistically significant. The mean postoperative
      deviation was 8(Delta) +/- 9(Delta) at distance and 7(Delta) +/- 9(Delta) at near
      in the conventional group and 9(Delta) +/- 8(Delta) at distance and 8(Delta) +/-
      8(Delta) at near in the anchored group. (P = 0.48 for distance, P = 0.98 for
      near). After 6 months, 63% of the conventional group and 60% of the anchored
      group were within 10(Delta) of orthophoria. Complications such as globe
      perforation, A and V patterns, and vertical deviations did not occur in either
      group. There were no statistically significant differences in the success rates
      (P = 0.79) or complications between the 2 groups. CONCLUSIONS: The placement of
      additional posterior scleral sutures to "anchor" the insertion did not improve
      outcomes in lateral rectus muscle recession surgery.

PMID- 22153396
TI  - Prevalence and course of strabismus through age 6 years in participants of the
      Early Treatment for Retinopathy of Prematurity randomized trial.
AB  - PURPOSE: To present strabismus data for children who participated in the Early
      Treatment for Retinopathy of Prematurity (ETROP) randomized trial. METHODS: The
      prevalence of strabismus, categorized as present or absent, was tabulated for all
      children with history of high-risk prethreshold retinopathy of prematurity (ROP)
      who participated in the ETROP randomized trial and were examined at 9 months to 6
      years of age. Relationships among strabismus and demographic measures, eye
      characteristics, and neurodevelopmental factors were analyzed. RESULTS: Among the
      342 children evaluated at 6 years, the prevalence of strabismus was 42.2%. Even
      with favorable acuity scores in both eyes, the prevalence of strabismus was
      25.4%, and with favorable structural outcomes in both eyes the prevalence of
      strabismus was 34.2%. Of children categorized as visually impaired as the result
      of either ocular or cerebral causes, 80% were strabismic at the 6-year
      examination. Of 103 study participants who were strabismic at 9 months, 77
      (74.8%) remained so at 6 years. Most strabismus was constant at both the 9-month
      (62.7%) and the 6-year examination (72.3%). After multiple logistic regression
      analysis, risk factors for strabismus were abnormal fixation behavior in one or
      both eyes (P < 0.001), history of amblyopia (P < 0.003), unfavorable structural
      outcome in one or both eyes (P = 0.025), and history of anisometropia (P = 0.04).
      Strabismus surgery was performed for 53 children. By 6 years, the cumulative
      prevalence of strabismus was 59.4%. CONCLUSIONS: Most children with a history of
      high-risk prethreshold ROP develop strabismus at some time during the first 6
      years of life.

PMID- 22153397
TI  - The association of refractive error, strabismus, and amblyopia with congenital
      ptosis.
AB  - PURPOSE: To determine the frequency of amblyopia and its associations among
      children with congenital ptosis. METHODS: A retrospective chart review of 92
      active patients with congenital ptosis in the practices of 2 of the authors. The
      main outcome measures were relative eyelid ptosis severity, presence and type of
      strabismus, refractive error, and amblyopia. RESULTS: Amblyopia was identified in
      22 of 92 patients (23.9%), in almost every case occurring in the context of
      coexisting anisometropia or strabismus and affecting the eye with the more severe
      ptosis (P = 0.0001). Amblyopia was more likely to occur in cases with greater
      relative eyelid asymmetry and did not develop in children with symmetric ptosis.
      In several cases, anisometropia and amblyopia were not initially apparent but
      progressively developed during follow-up. CONCLUSIONS: Children with congenital
      ptosis are at risk of anisometropic and strabismic amblyopia, which may progress
      during early development. Patients should be examined at regular intervals to
      evaluate and treat these potential complications.

PMID- 22153398
TI  - Changes in binocular function in anisometropic nonstrabismic children with
      optical correction and occlusion therapy.
AB  - PURPOSE: To identify factors that influence binocular function in anisometropic,
      nonstrabismic children before and after optical correction and amblyopia therapy.
      METHODS: This was a prospective observational study of consecutive patients with
      nonstrabismic anisometropia. Visual acuity and responses to the 4(Delta) base-out
      prism test, the Worth 4-dot test, and the TNO test were recorded after spectacle
      correction and every 3 months for 1 year. Factors affecting visual acuity and
      binocular function were analyzed using univariate and multiple stepwise
      regression analysis. RESULTS: A total of 118 subjects were enrolled. At the end
      of the first year, the mean improvement in visual acuity was 2.6 +/- 2.3 lines.
      The percentage of patients showing a positive response to the 4(Delta) base-out
      prism test increased from 47% to 79%; fusion in the Worth 4-dot test, from 37% to
      66%; and measurable stereopsis on TNO testing, from 59% to 80%. Better initial
      visual acuity and better final visual acuity were associated with better
      binocular function. Interocular refractive error difference was a predictor of
      poor binocular function in multiple regression analysis if the difference in
      spherical error exceeded 4 D. Patients with amblyopia showed significantly worse
      binocular function compared to those with no amblyopia. CONCLUSIONS: Binocular
      function of anisometropic children can be improved with refractive correction and
      amblyopia therapy.

PMID- 22153399
TI  - Modification of Plusoptix referral criteria to enhance sensitivity and
      specificity during pediatric vision screening.
AB  - PURPOSE: To determine the impact of using several different proposed sets of
      referral criteria on the specificity and sensitivity of the plusoptiX S08
      photoscreener for detecting amblyopia risk factors. METHODS: During a 2-month
      period, 144 children ages 9 months to 14 years were screened at the Tennessee
      Lions Eye Center before receiving a comprehensive eye examination and cycloplegic
      refraction. Three previously published sets of referral criteria were used for
      screening, including the manufacturer's criteria and the criteria proposed by
      Arthur and colleagues, which are nearly identical to the gold standard
      examination failure thresholds proposed by the Vision Screening Committee of the
      American Association of Pediatric Ophthalmology and Strabismus (AAPOS).
      Modifications of these criteria also were evaluated. The screening results
      obtained by the plusoptiX S08 were compared with the results from the gold
      standard pediatric ophthalmologic examination, and the respective sensitivities
      and specificities of each set of referral criteria in detecting amblyopia risk
      factors identified by the AAPOS Vision Screening Committee were calculated.
      RESULTS: The manufacturer's criteria yielded high sensitivity (100%) but very low
      specificity (37%). The Arthur criteria, which used the values for the AAPOS
      defined amblyopia risk factors as referral criteria, maintained sensitivity (89%)
      and greatly improved specificity (76%). Two modifications of the Arthur criteria
      further increased specificity with minimal loss of sensitivity. CONCLUSIONS: The
      manufacturer's criteria have excellent sensitivity but low specificity,
      warranting modification; other criteria increase specificity with minimal effect
      on sensitivity.

PMID- 22153400
TI  - Epidemiological characteristics and visual outcome after open globe injuries in
      children.
AB  - PURPOSE: To determine demographic, etiologic, clinical characteristics, visual
      outcome, and the factors affecting visual prognosis in children with open globe
      injuries. METHODS: The medical records of 82 patients under the age of 16 years
      who presented with open globe injuries from January 1998 to January 2009 were
      retrospectively examined. Age, sex, involved eye, cause, place of injury, wound
      location, presenting visual acuity, clinical signs, and final visual acuity were
      noted. The injuries were classified by Ocular Trauma Classification Group
      Guidelines and Birmingham Eye Trauma Terminology. RESULTS: Most injuries occurred
      in boys (54/82). The mean age was 8.4 +/- 3.7 years. Most patients (37.8%) were
      in the 3- to 6-year age group. All patients had a minimum of 6 months' follow-up
      (mean, 23.9 +/- 23.2 months; range, 6-114). Pointed metallic objects were found
      to be the main causative agents. Injuries occurred most frequently in streets
      (36.3%), homes (18.7%), leisure areas (15.4%), and schools (7.7%). Factors
      adversely affecting visual prognosis were poor presenting visual acuity,
      posterior wound location, low ocular trauma score, retinal detachment, afferent
      pupillary defect, vitreous prolapse, uveal tissue prolapse, and hyphema.
      CONCLUSIONS: Open globe injuries in children occur most frequently in preschool
      boys. Prognosis is determined by presenting visual acuity, trauma score, and
      wound severity and location.

PMID- 22153401
TI  - Ocular and systemic findings in a survey of aniridia subjects.
AB  - PURPOSE: To determine the prevalence of ocular and systemic abnormalities in a
      group of subjects with aniridia. METHODS: Survey forms developed by Aniridia
      Foundation International were sent to all members prior to the 2010 AFI member
      conference. An additional form was provided for completion by physicians caring
      for patients. Forms were then collected from all members who attended the
      meeting. RESULTS: A total of 155 surveys were distributed, of which 83 (53%) were
      completed. The mean age was 25.4 +/- 18.4 years, with 65% sporadic and 35%
      familial cases, and 2.4% with WAGR (Wilms' tumor, aniridia, genitourinary
      anomalies, and mental retardation) syndrome. Ocular abnormalities included
      nystagmus (83%), cataract (71%), dry eye (53%), glaucoma (46%), keratopathy
      (45%), foveal hypoplasia (41%), strabismus (31%), and retinal disease (5%). The
      mean age at diagnosis of aniridia was 22.1 months (median, 1.5 months) and
      glaucoma was 13.6 years (median, 8.5 years). Of 38 subjects with aniridia and
      glaucoma, 76% were treated medically, and 58% had been treated surgically. In
      subjects with glaucoma, the mean number (+/- SD) of glaucoma medications was 1.8
      +/- 1.3, and number of surgical procedures was 1.7 +/- 2.0. Developmental delay
      was reported in 17%. The mean body mass index and the prevalence of obesity in
      subjects with aniridia was significantly greater (P = 0.003) than in siblings
      without aniridia. CONCLUSIONS: In this study, aniridia was associated with
      nystagmus and other motility problems, cataract, glaucoma, and keratopathy.
      Systemic abnormalities included increased average body mass index and obesity,
      which appeared to occur not only in WAGR syndrome but more broadly in aniridia.

PMID- 22153402
TI  - Feasibility and quality of nonmydriatic fundus photography in children.
AB  - PURPOSE: Ocular funduscopic examination is difficult in young children and is
      rarely attempted by nonophthalmologists. Our objective was to determine the
      feasibility of reliably obtaining high-quality nonmydriatic fundus photographs in
      children. METHODS: Nonmydriatic fundus photographs were obtained in both eyes of
      children seen in a pediatric ophthalmology clinic. Ease of fundus photography was
      recorded on a 10-point Likert scale (10 = very easy). Quality was graded from 1
      to 5 (1, inadequate for any diagnostic purpose; 2, unable to exclude all emergent
      findings; 3, only able to exclude emergent findings; 4, not ideal, but still able
      to exclude subtle findings; and 5, ideal quality). The primary outcome measure
      was image quality by age. RESULTS: A total of 878 photographs of 212 children
      (median age, 6 years; range, 1-18 years) were included. Photographs of at least
      one eye were obtained in 190 children (89.6%) and in both eyes in 181 (85.3%).
      Median rating for ease of photography was 7. Photographs of some clinical value
      (grade >=2) were obtained in 33% of children <3 years and 95% >=3 years. High
      quality photographs (grade 4 or 5) were obtained in both eyes in 7% of children
      <3 years, 57% of children >=3 to <7 years, 85% of children >=7 to <9 years, and
      65% of children >=9 years. The youngest patient with high-quality photographs in
      both eyes was 22 months. CONCLUSIONS: Nonmydriatic fundus photographs of adequate
      quality can be obtained in children over age 3 and in some children as young as
      22 months.

PMID- 22153403
TI  - Accuracy of retinopathy of prematurity image-based diagnosis by pediatric
      ophthalmology fellows: implications for training.
AB  - PURPOSE: To measure the accuracy of image-based retinopathy of prematurity (ROP)
      diagnosis by pediatric ophthalmology fellows. METHODS: This was a comparative
      case series of expert versus nonexpert clinicians in image-based ROP diagnosis.
      An atlas of 804 retinal images was captured from 248 eyes of 67 premature infants
      with a wide-angle camera (RetCam-II, Clarity Medical Systems, Pleasanton, CA).
      Images were uploaded to a study website from which an expert pediatric retinal
      specialist and five pediatric ophthalmology fellows independently provided a
      diagnosis (no ROP, mild ROP, type 2 ROP, or treatment-requiring ROP) for each
      eye. Two different retinal specialists experienced in ROP examination served as
      additional controls. Primary outcome measures were sensitivity and specificity of
      image-based ROP diagnosis by fellows compared to a reference standard of image
      based interpretation by the expert pediatric retinal specialist. Secondary
      outcome measure was intraphysician reliability. RESULTS: For detection of mild or
      worse ROP, the mean (range) sensitivity among the five fellows was 0.850 (0.670
      0.962) and specificity was 0.919 (0.832-0.964). For detection of type 2 or worse
      ROP by fellows, mean (range) sensitivity was 0.527 (0.356-0.709) and specificity
      was 0.938 (0.777-1.000). For detection of treatment-requiring ROP, mean (range)
      sensitivity was 0.515 (0.267-0.765) and specificity was 0.949 (0.805-1.00).
      CONCLUSIONS: Pediatric ophthalmology fellows in this study demonstrated high
      diagnostic specificity in image-based ROP diagnosis; however, sensitivity was
      lower, particularly for clinically significant disease.

PMID- 22153406
TI  - Augmented vertical rectus [corrected] transposition for the treatment of
      strabismus in Mobius syndrome.
AB  - Mobius syndrome is a rare congenital disorder characterized by bilateral facial
      nerve palsy and abducens nerve palsy. It is associated with a wide spectrum of
      systemic and ocular manifestations; esotropia is commonly the reason for
      ophthalmic referral. There are few published studies in the literature on
      strabismus surgery in Mobius syndrome. An augmented vertical rectus muscle
      transposition in which lateral fixation sutures are used on the transposed
      vertical rectus muscles (Foster augmentation) has been used to correct esotropia
      caused by severe sixth nerve palsy and type 1 Duane syndrome. We describe the
      surgical outcome after treating moderate- to large-angle esotropia in 3 patients
      with Mobius syndrome with the augmented vertical rectus muscle transposition.

PMID- 22153405
TI  - Isolated abducens nerve palsy secondary to Lemierre syndrome.
AB  - Lemierre syndrome is characterized by pharyngotonsillitis that is typically
      secondary to Fusobacterium necrophorum infection and causes adjacent septic
      thrombophlebitis and thrombosis with subsequent metastatic abscesses. A 3-year
      old boy presented with fever, tonsillar enlargement, and bilateral otomastoiditis
      with purulent discharge. Physical examination revealed abducens nerve palsy on
      the left side, with a compensatory left head turn. Otomastoid discharge culture
      was positive for anaerobic F. necrophorum. Magnetic resonance venography of the
      head and neck revealed thromboses in left internal jugular vein, left cavernous
      sinus, left superior ophthalmic vein, and left sigmoid sinus. The patient was
      treated with anticoagulation and a 10-week course of intravenous antibiotics,
      including ceftriaxone and metronidazole.

PMID- 22153404
TI  - Unilateral sporadic retinal dysplasia: results of histopathologic,
      immunohistochemical, chromosomal, genetic, and VEGF-A analyses.
AB  - PURPOSE: To describe new findings in a case of unilateral retinal dysplasia.
      METHODS: Histopathologic evaluation of an enucleated globe and analysis with
      immunohistochemical probes, karyotyping, and genetic analysis for the Norrie
      gene, and aqueous assay for vascular endothelial growth factor A (VEGF-A).
      RESULTS: Histopathological examination of the globe revealed retinal dysplasia
      with pseudorosette formation, abnormal or absent retinal nuclear lamination, a
      paucity of disorganized retinal microvasculature, retinal infoldings, advanced
      gliosis, persistent hyperplastic vitreous, exuberant neovascularization of the
      vitreous, and iris neovascularization (identical to the findings observed in
      bilateral Norrie disease). Immunohistochemistry disclosed GFAP-positive and GLUT
      1-positive gliosis and retinal and persistent hyperplastic vitreous microvessels
      that were CD34-positive and GLUT-1-negative. Ki-67-positive retinal cells were
      polarized toward the subretinal space and absent in the retinal invaginations and
      pseudorosettes. A normal karyotype was found, and DNA sequencing revealed no
      known mutation in the region of the Norrie gene (NDP) in sputum or retinal DNA.
      Aqueous obtained immediately after enucleation contained an exceptionally high
      concentration of VEGF-A (4.5 ng/mL). CONCLUSIONS: Despite the failure to find an
      abnormal NDP allele, other unexplored NDP regions, an undetected defect
      restricted to retinal tissues, or an autosomal mutation coupled with disrupted
      signaling pathways may be responsible for the condition. High aqueous VEGF-A
      suggests that this cytokine may play a role in pathogenesis in conjunction with
      other pathways.

PMID- 22153407
TI  - Congenital absence of the superior oblique tendon in Noonan-neurofibromatosis
      syndrome.
AB  - A 5-year-old girl with Noonan-neurofibromatosis syndrome was diagnosed with
      bilateral superior oblique palsy. At surgery, the right superior oblique tendon
      was absent, and further exploration revealed abnormal tissue inserting into
      Tenon's capsule. Orbital imaging was not performed. Congenital absence of the
      superior oblique tendon was diagnosed. Although Noonan syndrome is known to have
      many ocular manifestations, absence of the superior oblique tendon has not been
      previously reported.

PMID- 22153408
TI  - Positional ocular flutter and thickened optic nerves as sentinel signs of Krabbe
      disease.
AB  - A 5-month-old boy developed a large-amplitude, horizontal pendular flutterlike
      oscillation of the eyes, when placed in the supine position. Magnetic resonance
      imaging (MRI) 1 month earlier had shown isolated thickening of the optic nerves
      and chiasm without other central nervous system signal abnormalities. Repeat MRI
      at 51/2 months of age showed a constellation of central nervous system signal
      abnormalities suggestive of Krabbe disease. The diagnosis was confirmed with
      serum enzymatic and genetic testing. This case demonstrates that positional
      ocular flutter can be a presenting sign of Krabbe disease and reinforces the
      observation that isolated thickening of the anterior visual pathways can antedate
      other central nervous system abnormalities on MRI.

PMID- 22153409
TI  - Juvenile xanthogranulomatosis with bilateral and multifocal ocular lesions of the
      iris, cornealscleral limbus, and choroid.
AB  - A 14-month-old boy with juvenile xanthogranuloma skin lesions presented with
      increased intraocular pressure, hyphema, anterior uveitis, iris mass, and a
      subconjunctival limbal mass of the right eye. He subsequently developed a
      subretinal mass in the left eye. The anterior uveitis resolved after 2 periocular
      injections of triamcinolone in addition to the administration of topical
      prednisolone and oral prednisone and methotrexate. The subretinal mass in the
      left eye also resolved during the course of 1 year. He developed a cataract in
      the right eye and underwent lensectomy with anterior vitrectomy. This is the
      first published case in which methotrexate was used as an adjunctive treatment of
      juvenile xanthogranuloma in a child.

PMID- 22153410
TI  - Congenital intradiploic arachnoid cyst presenting as painless proptosis.
AB  - A 12-year-old girl presented with several years of progressive painless proptosis
      and orbital fullness. On imaging, she was found to have marked expansion and
      remodeling centered in the right greater wing of the sphenoid bone with an
      adjacent middle cranial fossa arachnoid cyst. A clinical diagnosis of
      intradiploic arachnoid cyst was made. This entity was benign, and other
      ophthalmic and neurologic signs or symptoms were absent. Our patient was observed
      without surgical intervention. To our knowledge, this is the first such case
      reported in a child. Although this cyst has been described in the occipital and
      frontal bones, this is the first description of occurrence in the sphenoid bone.

PMID- 22153411
TI  - Persistent pupillary membrane, strabismus, and optic nerve hypoplasia in Donnai
      Barrow syndrome.
AB  - We report a case of Donnai-Barrow syndrome in a 2-year-old boy who presented with
      exotropia and prominent eyes since birth. Ocular findings included high myopia,
      persistent pupillary membrane, and optic nerve hypoplasia. Facial manifestations
      included broad nasal bridge, hypertelorism, and downward-slanting of palpebral
      fissures. The patient had associated omphalocele, sensorineural hearing loss, and
      developmental delay. Magnetic resonance imaging revealed agenesis of the corpus
      callosum. To our knowledge, this is the first reported association of persistent
      pupillary membrane, strabismus, and optic nerve hypoplasia in a patient with
      Donnai-Barrow syndrome.

PMID- 22153412
TI  - Uveal melanoma in a 19-month-old child.
AB  - Uveal melanoma is extremely rare in children. Its clinical and histopathological
      features have been reported to be similar to those observed in adults. The tumor
      usually presents as a sessile or dome-shaped mass with secondary
      nonrhegmatogenous retinal detachment. We report a 19-month-old boy with a
      choroidal melanoma presenting as hemorrhagic retinal detachment and buphthalmos.
      The eye was enucleated, but the child subsequently died from systemic metastases.

PMID- 22153414
TI  - Seasonal variation in visceral fat and blood HbA1c in people with type 2
      diabetes.

PMID- 22153413
TI  - Widespread retinal hemorrhages after retinopathy of prematurity screening with
      scleral depression.
AB  - We report a case of extensive bilateral intraretinal hemorrhages in a premature
      infant with active retinopathy of prematurity (ROP) after an examination with
      scleral depression. In the only other previously reported case, the retinal
      hemorrhages were limited to the posterior pole of an eye with preexisting
      vitreous hemorrhage, and the child had a history of severe necrotizing
      enterocolitis that required surgery. Investigators have hypothesized that the
      combination of ocular manipulation, abrupt intraocular pressure change, and
      fragile immature retinal vasculature with poor autoregulation may contribute to
      the pathogenesis of retinal hemorrhages. Physicians performing ROP examinations
      should be aware of this possibility and judiciously use scleral depression;
      however, examination-induced retinal hemorrhages in children have never been
      reported in the absence of active ROP.

PMID- 22153415
TI  - Precipitating factors of diabetic ketoacidosis at a public hospital in a middle
      income country.
AB  - AIMS: To study precipitating factors of diabetic ketoacidosis (DKA) at a public
      hospital in a middle-income country. METHODS: Eighty patients with type 1
      diabetes who had an emergency hospitalization for DKA between January 2005 and
      March 2010 at a tertiary care teaching hospital in Southern Brazil were studied.
      Data were collected by reviewing medical records and telephone calls. Treatment
      non-adherence was defined as the precipitating factor if there was diet abuse or
      insulin therapy noncompliance without identifiable infection. RESULTS: The mean
      age of patients was 26+/-13 years. The majority (91.5%) of the patients had
      unsatisfactory metabolic control before the hospitalization. The most common DKA
      precipitating factor was treatment non-adherence: 39% of cases when all patients
      were evaluated and 49% when only patients with previous type 1 diabetes diagnosis
      were analyzed. Comparison between patients with DKA precipitated by treatment non
      adherence and by other causes showed that the former group had more episodes of
      previous DKA and more frequently reported insulin omission previous to DKA.
      CONCLUSIONS: Treatment noncompliance is the leading precipitating factor of DKA
      in Southern Brazil. Further efforts to reduce the occurrence of DKA should focus
      on patients with prior reports and evidence of treatment non-adherence.

PMID- 22153416
TI  - Screening and intervention of diabetes mellitus in patients with pulmonary
      tuberculosis in poverty zones in China: rationale and study design.
AB  - BACKGROUND: The merging epidemics of pulmonary tuberculosis (PTB) and diabetes
      mellitus (DM) have been raised concerns by many experts but no large scale
      screening and intervention have been launched yet, especially in low-income
      areas. The current study aims to understand the prevalence of DM in active PTB
      patients and evaluate the outcomes of diet and living habit intervention in
      poverty zones in China. METHODS/DESIGN: A cross-sectional investigation and
      intervention study will be carried out. At least 7000 active PTB patients will be
      recruited, together with 7000 nonTB persons from the same community. The project
      will be divided into two stages. The first stage is to train TB workers on DM
      screening and regular treatment. Screening and related investigation will be
      carried out afterwards. The second stage is focussed on intervention. A
      comprehensive strategy will be utilized to conduct health promotion among the
      patients, the health providers and the lay public. DISCUSSION: To our knowledge,
      this is the first and largest study which focuses on the prevalence of DM in PTB
      in China. We hypothesize that the current prevalence of DM in PTB in China will
      be understood and the results of our study will provide important evidence for
      preventing and controlling DM and PTB.

PMID- 22153417
TI  - The management of Type 2 diabetes: a survey of Australian general practitioners.
AB  - OBJECTIVE: To explore how clinical and demographic variables impact on the
      management of diabetes mellitus in general practice. DESIGN: A structured
      vignette survey was conducted in Australia. This included nine vignettes chosen
      at random from 128 developed around seven clinical variables. Respondents were
      asked to recommend a change in treatment and make specific recommendations. A
      random sample of general practitioners (GPs) were recruited. Two diabetologists
      involved in the development of national guidelines also participated. RESULTS:
      125 (13.8%) GPs participated. Statistical analyses were used to generate outcome
      measures. GPs recommended a change in treatment for most (81.1%) cases; were less
      likely to prescribe a statin (68.5% GPs vs. 76.3% diabetologists), less likely to
      treat hypertension (66.7% vs.89%) and less likely to refer for lifestyle
      modification (82.3% vs. 96.5%). Significant disagreement occurred around
      prescribing or changing oral hypoglycaemics. No GP characteristics showed
      significant impact. The proportion of GPs who agreed with diabetiologists on dose
      and choice of drugs was 35.7% for statins, 49.6% for antihypertensives and 39.6%
      for oral hypoglycaemics. CONCLUSIONS: There were significant differences between
      diabetologists and GPs on the management of diabetes. The survey suggests
      significant under-dosing by GPs. These findings warrant further investigation.

PMID- 22153418
TI  - Re: Prevalence of baseline chronic kidney disease in patients presenting with
      solid renal tumors.

PMID- 22153419
TI  - Re: Thermal ablation vs surgery for localized kidney cancer: a surveillance,
      epidemiology, and end results (seer) database analysis.

PMID- 22153420
TI  - Re: Outcomes of small renal mass needle core biopsy, nondiagnostic percutaneous
      biopsy, and the role of repeat biopsy.

PMID- 22153421
TI  - Re: The impact of previous ureteroscopic tumor ablation on oncologic outcomes
      after radical nephrouretectomy for upper urinary tract urothelial carcinoma.

PMID- 22153422
TI  - Re: Ureteral and multifocal tumours have worse prognosis than renal pelvic
      tumours in urothelial carcinoma of the upper urinary tract treated by
      nephroureterectomy.

PMID- 22153423
TI  - Re: BioGlue iceball stabilization to minimize the risk of hemorrhage during
      laparoscopic renal cryoablation.

PMID- 22153424
TI  - Re: Perioperative, oncologic, and functional outcomes of laparoscopic renal
      cryoablation and open partial nephrectomy: a matched pair analysis.

PMID- 22153425
TI  - Re: Smoking and prostate cancer survival and recurrence.

PMID- 22153426
TI  - Re: Association of clinical benign prostate hyperplasia with prostate cancer
      incidence and mortality revisited: a nationwide cohort study of 3,009,258 men.

PMID- 22153427
TI  - Re: A novel two-stage, transdisciplinary study identifies digoxin as a possible
      drug for prostate cancer treatment.

PMID- 22153428
TI  - Re: Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate
      cancer in men treated with dutasteride: lessons from the REDUCE study.

PMID- 22153429
TI  - Re: Significance of incidental focal uptake in prostate on 18-fluoro-2
      deoxyglucose positron emission tomography CT images.

PMID- 22153430
TI  - Re: A contemporary population-based assessment of the rate of lymph node
      dissection for penile carcinoma.

PMID- 22153431
TI  - Re: Public perceptions of the harms and benefits of testicular cancer education:
      a qualitative study.

PMID- 22153432
TI  - Re: Risk factors for fluoroquinolone-resistant Escherichia coli in adults with
      community-onset febrile urinary tract infection.

PMID- 22153434
TI  - Re: Morphological plasticity promotes resistance to phagocyte killing of
      uropathogenic Escherichia coli.

PMID- 22153436
TI  - Re: Reliability of superficial surgical site infections as a hospital quality
      measure.

PMID- 22153435
TI  - Re: Surgical site infection and analytic morphometric assessment of body
      composition in patients undergoing midline laparotomy.

PMID- 22153437
TI  - Re: Urodynamics, the supine empty bladder stress test, and incontinence severity.

PMID- 22153438
TI  - Re: Retropubic versus transobturator midurethral slings for stress incontinence.

PMID- 22153439
TI  - Re: Should an anti-incontinence procedure be routinely performed at the time of
      pelvic organ prolapse repair? an evidence-based review.

PMID- 22153440
TI  - Re: Are multichannel urodynamics required prior to surgery in a woman with stress
      urinary incontinence?

PMID- 22153441
TI  - Re: Translation of evidence into a self-management tool for use by women with
      urinary incontinence.

PMID- 22153442
TI  - Re: In-hospital use of continence AIDS and new-onset urinary incontinence in
      adults aged 70 and older.

PMID- 22153443
TI  - Re: Association of cancer with geriatric syndromes in older medicare
      beneficiaries.

PMID- 22153445
TI  - Re: Systematic review and meta-analysis: do clinical trials testing
      antimuscarinic agents for overactive bladder adequately measure central nervous
      system adverse events?

PMID- 22153444
TI  - Re: Risk factors for overactive bladder in the elderly population: a community
      based study with face-to-face interview.

PMID- 22153446
TI  - Re: The efficacy of additive tolterodine extended release for 1-year in older men
      with storage symptoms and clinical benign prostatic hyperplasia.

PMID- 22153447
TI  - Re: Transurethral ethanol ablation of the prostate for symptomatic benign
      prostatic hyperplasia: long-term follow-up.

PMID- 22153448
TI  - Re: Prostatic arterial embolization to treat benign prostatic hyperplasia.

PMID- 22153449
TI  - Re: A placebo-controlled study investigating the efficacy and safety of the
      phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of men with lower
      urinary tract symptoms associated with clinical benign prostatic hyperplasia.

PMID- 22153451
TI  - Re: Attitudes toward management of decreased sexual desire in premenopausal
      women: a national survey of nurse practitioners and physician assistants.

PMID- 22153452
TI  - Re: Recent and Lifelong sexual dysfunction in a female UK population sample:
      prevalence and risk factors.

PMID- 22153453
TI  - Re: Sexual function in female patients with obstructive sleep apnea.

PMID- 22153455
TI  - Re: Testosterone Deficiency is a Cause of Anaemia and Reduced Responsiveness to
      Erythropoiesis-Stimulating Agents in Men With Chronic Kidney Disease.

PMID- 22153454
TI  - Re: Testosterone gel replacement improves sexual function in depressed men taking
      serotonergic antidepressants: a randomized, placebo-controlled clinical trial.

PMID- 22153456
TI  - Re: Anti-infection dip suggestions for the coloplast titan inflatable penile
      prosthesis in the era of the infection retardant coated implant.

PMID- 22153457
TI  - Re: Early insertion of inflatable prosthesis for intractable ischemic priapism:
      our experience and review of the literature.

PMID- 22153458
TI  - Re: Regulation of male fertility by the opioid system.

PMID- 22153460
TI  - Re: Prenatal and adult exposures to smoking are associated with adverse effects
      on reproductive hormones, semen quality, final height and body mass index.

PMID- 22153461
TI  - Re: The relationship between anogenital distance, fatherhood, and fertility in
      adult men.

PMID- 22153462
TI  - Re: Are serum levels of vitamin d associated with semen quality? Results from a
      cross-sectional study in young healthy men.

PMID- 22153463
TI  - Re: Bone mineral density and testicular failure: evidence for a role of vitamin D
      25-hydroxylase in human testis.

PMID- 22153465
TI  - Re: An investigation of the potential effect of vacuoles in human sperm on DNA
      damage using A chromosome assay and the TUNEL assay.

PMID- 22153464
TI  - Re: Analysis of the outcome of intracytoplasmic sperm injection using fresh or
      frozen sperm.

PMID- 22153466
TI  - Re: Copy number variants in patients with severe oligozoospermia and sertoli-cell
      only syndrome.

PMID- 22153467
TI  - Re: Physical activity and semen quality among men attending an infertility
      clinic.

PMID- 22153468
TI  - Re: Satisfaction profiles in men using intracavernosal injection therapy.

PMID- 22153469
TI  - Re: Paternal body mass index is associated with decreased blastocyst development
      and reduced live birth rates following assisted reproductive technology.

PMID- 22153470
TI  - Re: Fifteen-year trend in the use of male reproductive surgery: analysis of the
      healthcare cost and utilization project data.

PMID- 22153471
TI  - Re: Solitary urethrocutaneous fistula managed by the PATIO repair.

PMID- 22153472
TI  - Re: Does androgen stimulation prior to hypospadias surgery increase the rate of
      healing complications? A preliminary report.

PMID- 22153473
TI  - Re: The microvessel density of the hypospadiac prepuce in children.

PMID- 22153474
TI  - Re: Outcome analysis of tubularized incised urethral plate using dorsal dartos
      flap for proximal penile hypospadias repair.

PMID- 22153475
TI  - Re: Risk factors for re-operation following tubularized incised plate
      urethroplasty: a comprehensive analysis.

PMID- 22153476
TI  - Re: TRPA1 receptor modulation attenuates bladder overactivity induced by spinal
      cord injury.

PMID- 22153477
TI  - Re: Testosterone replacement effectively inhibits the development of experimental
      autoimmune orchitis in rats: evidence for a direct role of testosterone on
      regulatory T cell expansion.

PMID- 22153478
TI  - Re: Hypoxia-inducible factor and mammalian target of rapamycin pathway markers in
      urothelial carcinoma of the bladder: possible therapeutic implications.

PMID- 22153483
TI  - High school dropouts: interactions between social context, self-perceptions,
      school engagement, and student dropout.
AB  - Research suggests that contextual, self-system, and school engagement variables
      influence dropping out from school. However, it is not clear how different types
      of contextual and self-system variables interact to affect students' engagement
      or contribute to decisions to dropout from high school. The self-system model of
      motivational development represents a promising theory for understanding this
      complex phenomenon. The self-system model acknowledges the interactive and
      iterative roles of social context, self-perceptions, school engagement, and
      academic achievement as antecedents to the decision to dropout of school. We
      analyzed data from the Education Longitudinal Study of 2002-2004 in the context
      of the self-system model, finding that perception of social context (teacher
      support and parent support) predicts students' self-perceptions (perception of
      control and identification with school), which in turn predict students' academic
      and behavioral engagement, and academic achievement. Further, students' academic
      and behavioral engagement and achievement in 10th grade were associated with
      decreased likelihood of dropping out of school in 12th grade.

PMID- 22153484
TI  - Spectroscopic study of the degradation of antibiotics and the generation of
      representative EfOM oxidation products in ozonated wastewater.
AB  - This study examined effects of ozonation on thirteen fluoroquinolone, macrolide
      and lincosamide antibiotics present in municipal wastewater. Transformations of
      effluent organic matter (EfOM) caused by ozonation were characterized using
      absorbance/fluorescence spectroscopy and high performance size exclusion
      chromatography (HPSEC). Concentrations of aldehydes and carboxylic acids
      generated via the oxidation of EfOM were also determined. The absorbance and
      fluorescence of ozonated wastewater decreased with increasing ozone dose or
      treatment time. HPSEC data showed that these phenomena corresponded to the
      oxidation of all EfOM fractions, with some preference towards the degradation of
      the EfOM molecules with high apparent molecular weight. The removal of
      antibiotics and production of aldehydes and carboxylic acids were strongly
      correlated with the changes in both EfOM absorbance and fluorescence.
      Applications of a model describing the concurrent degradation of trace level
      contaminants and relative changes of EfOM emission allowed achieving a good
      fitting between the experimental and modeled DeltaC/C(0) vs. DeltaA/A(0) and
      DeltaC/C(0) vs. DeltaF/F(0) data.

PMID- 22153485
TI  - A rapid method for screening of the Stockholm Convention POPs in small amounts of
      human plasma using SPE and HRGC/HRMS.
AB  - A rapid analytical screening method allowing simultaneous analysis of 23
      persistent organic pollutants (POPs) in human plasma was developed. Sample
      preparation based on solid-phase extraction (SPE) with additional clean-up using
      small multilayer silica gel columns. SPE was performed using a custom made
      polystyrene-divinylbenzene sorbent for the extraction of chlorinated and
      brominated POPs. Special efforts to reduce sample volume and improve speed and
      efficiency of the analytical procedure were made. Determination of 16
      polychlorinated biphenyls (PCBs), 5 organochlorine (OC) pesticides,
      octachlorinated dibenzo-p-dioxin (OCDD) and polybrominated diphenyl ether (BDE
      #47) in 0.5 mL human plasma was performed by using high resolution gas
      chromatography coupled to high resolution mass spectrometry (HRGC/HRMS). Recovery
      of POPs ranged between 46% and 110%, and reproducibility was below 25% relative
      standard deviation (RSD) for all target compounds, except for trans-nonachlor and
      OCDD, which were present only at low levels. Limits of detection (LOD) were for
      the PCBs between 0.8 and 117.7 pg mL(-1) plasma and for the OC pesticides between
      5.9 and 89.1 pg mL(-1) plasma. The LOD for OCDD and BDE #47 were 1.4 pg mL(-1)
      plasma, and 9.2 pg mL(-1) plasma, respectively. The presented method was
      successfully applied to 1016 human plasma samples from an epidemiological study
      on cardiovascular disease.

PMID- 22153486
TI  - Reduction of Cr(VI) by malic acid in aqueous Fe-rich soil suspensions.
AB  - Detoxification of Cr(VI) through reduction by organic reductants has been
      regarded as an effective way for remediation of Cr(VI)-polluted soils. However,
      such remediation strategy would be limited in practical applications due to the
      low Cr(VI) reduction rate. In this study, the catalytic effect of two Fe-rich
      soils (Ultisol and Oxisol) on Cr(VI) reduction by malic acid was evaluated. As
      the results shown, the two soils could obviously accelerate the reduction of
      Cr(VI) by malic acid at low pH conditions, while such catalytic effect was
      gradually suppressed as the increase in pH. After reaction for 48 h at pH 3.2,
      Oxalic acid was found in the supernatant of Ultisol, suggesting the oxidization
      of hydroxyl in malic acid to carboxyl and breakage of the bond between C(2) and
      C(3). It was also found that the catalytic reactivity of Ultisol was more
      significant than that of Oxisol, which could be partly attributed to the fact
      that the amount of Fe(II) released from the reductive dissolution of Ultisol by
      malic acid was larger than that of Oxisol. With addition of Al(III), the
      catalytic effect from Ultisol was inhibited across the pH range examined. On the
      contrary, the presence of Cu(II) would increase the catalytic effect of Ultisol,
      which was more pronounced with the increase in pH. This study proposed a
      potential way for elimination of the environmental risks posed by the Cr(VI)
      contamination by use of the natural soil surfaces to catalyze Cr(VI) reduction by
      the organic reductant such as malic acid, a kind of organic reductant originating
      from soil organic decomposition process or plant excretion.

PMID- 22153487
TI  - High cardiovascular morbidity and mortality in myofibrillar myopathies due to DES
      gene mutations: a 10-year longitudinal study.
AB  - To determine incidence and type of major cardiac adverse events in patients with
      mutated desmin (DES) gene, we retrospectively reviewed baseline medical
      information, and examined the long-term outcomes of 28 DES patients (17 men,
      baseline mean age=37.7+/-14.4 years [min=9, max=71]) from 19 families. Baseline
      studies revealed skeletal muscle involvement in 21 patients and cardiac
      abnormalities in all but one patient. Over a mean follow-up of 10.4+/-9.4 years
      [min=1, max=35], cardiac death occurred in three patients, death due to cardiac
      comorbidities in two, one or more major cardiac adverse events in 13 patients.
      Among the 19 patients with mild conduction defects at baseline, eight developed
      high-degree conduction blocks requiring permanent pacing. Cardiac involvement was
      neither correlated with the type of DES mutation nor with the severity of
      skeletal muscle involvement. Our study underscores that in DES patients in-depth
      cardiac investigations are needed to prevent cardiac conduction system disease.

PMID- 22153488
TI  - Massive transfusion protocols for patients with substantial hemorrhage.

PMID- 22153489
TI  - Facets of impulsivity in the relationship between antisocial personality and
      abstinence.
AB  - Most individuals who enter drug treatment programs are unable to maintain long
      term abstinence. This problem is especially relevant for those presenting with
      Antisocial Personality Disorder (ASPD). In examining potential mechanisms
      underlying the relationship between ASPD and abstinence, one factor that may be
      especially useful is the personality variable of impulsivity. Thus, the current
      study examined ASPD status in relation to longest abstinence attempt among 117
      substance use treatment-seeking individuals, considering the mediating role of
      five facets of impulsivity: urgency, perseverance, premeditation, control, and
      delay discounting. Results indicated that individuals with ASPD evidenced shorter
      previous abstinence attempts and lower levels of perseverance and control than
      those without ASPD. Further, lower levels of control were associated with shorter
      abstinence attempts. Finally, control mediated the relationship between ASPD and
      longest quit attempt. These results suggest the potential value of multiple
      facets of impulsivity in efforts to understand relapse and subsequent treatment
      development efforts.

PMID- 22153490
TI  - Face-to-face, pak-to-pak.
AB  - Biochemical and structural studies of p21-activated kinase 1 (Pak1) by Wang and
      colleagues in this issue of Structure reveal the structural basis for Pak1 trans
      autophosphorylation of the activation loop, a critical step in the activation of
      kinases.

PMID- 22153491
TI  - Progress at last.
AB  - Refinement of protein structures from a correct topology to atomically detailed
      resolution has proven remarkably difficult. Jian et al. (in this issue of
      Structure) illustrate a significant advance in this task by carefully
      incorporating into the refinement process many body interactions extracted from
      fragment statistics.

PMID- 22153492
TI  - Phosphorylation at the interface.
AB  - Proteomic studies have identified thousands of eukaryotic phosphorylation sites
      (phosphosites), but few are functionally characterized. Nishi et al., in this
      issue of Structure, characterize phosphosites at protein-protein interfaces and
      estimate the effect of their phosphorylation on interaction affinity, by
      combining proteomics data with protein structures.

PMID- 22153493
TI  - Creating order out of disorder: structural imprint of GAPDH on CP12.
AB  - The work presented by Matsumura et al. in this issue of Structure describes the
      structure of the ternary GAPDH-NAD-CP12 and the binary NAD-GAPDH complex in the
      cyanobacterium Synechococcus elongatus.

PMID- 22153494
TI  - Terpenoid synthases--from chemical ecology and forest fires to biofuels and
      bioproducts.
AB  - Terpenoids are a diverse group of natural products with a myriad functions in
      ecological interactions of living organisms. Terpenoid synthases provide a unique
      reservoir of enzymes for the metabolic engineering of advanced biofuels and high
      value bioproducts (McAndrew et al. in this issue of Structure).

PMID- 22153495
TI  - First crystal structures of Na+,K+-ATPase: new light on the oldest ion pump.
AB  - Na(+),K(+)-adenosine triphosphatase (NKA) is the first P-type ion translocating
      adenosine triphosphatase (ATPase) ever identified, and the significance of this
      class of proteins was highlighted by the 1997 Nobel Prize in Chemistry awarded to
      Jens C. Skou for the discovery in 1957. More than half a century passed between
      the initial identification and the publication of a high-resolution crystal
      structure of NKA. Although the new crystal structures provided many surprises and
      insights, structural biology on this system remains challenging, as NKA is a very
      difficult protein to crystallize. Here we explain the reasons behind the
      challenges, introduce a mechanism that governs the function, and summarize
      current knowledge of NKA structure in comparison with another member of the P
      type ATPase family, Ca(2+)-ATPase.

PMID- 22153496
TI  - Real space refinement of crystal structures with canonical distributions of
      electrons.
AB  - Recurring groups of atoms in molecules are surrounded by specific canonical
      distributions of electrons. Deviations from these distributions reveal
      unrealistic molecular geometries. Here, we show how canonical electron densities
      can be combined with classical electron densities derived from X-ray diffraction
      experiments to drive the real space refinement of crystal structures. The
      refinement process generally yields superior molecular models with reduced excess
      electron densities and improved stereochemistry without compromising the
      agreement between molecular models and experimental data.

PMID- 22153497
TI  - Automated prediction of protein association rate constants.
AB  - The association rate constants (k(a)) of proteins with other proteins or other
      macromolecular targets are a fundamental biophysical property. Observed rate
      constants span over ten orders of magnitude, from 1 to 10(10) M(-1)s(-1). Protein
      association can be rate limited either by the diffusional approach of the
      subunits to form a transient complex, with near-native separation and orientation
      but without short-range native interactions, or by the subsequent conformational
      rearrangement to form the native complex. Our transient-complex theory showed
      promise in predicting k(a) in the diffusion-limited regime. Here, we develop it
      into a web server called TransComp (http://pipe.sc.fsu.edu/transcomp/) and report
      on the server's accuracy and robustness based on applications to over 100 protein
      complexes. We expect this server to be a valuable tool for systems biology
      applications and for kinetic characterization of protein-protein and protein
      nucleic acid association in general.

PMID- 22153498
TI  - Structural insights into the autoactivation mechanism of p21-activated protein
      kinase.
AB  - p21-activated kinases (PAKs) play an important role in diverse cellular
      processes. Full activation of PAKs requires autophosphorylation of a critical
      threonine/serine located in the activation loop of the kinase domain. Here we
      report crystal structures of the phosphorylated and unphosphorylated PAK1 kinase
      domain. The phosphorylated PAK1 kinase domain has a conformation typical of all
      active protein kinases. Interestingly, the structure of the unphosphorylated PAK1
      kinase domain reveals an unusual dimeric arrangement expected in an authentic
      enzyme-substrate complex, in which the activation loop of the putative
      "substrate" is projected into the active site of the "enzyme." The enzyme is
      bound to AMP-PNP and has an active conformation, whereas the substrate is empty
      and adopts an inactive conformation. Thus, the structure of the asymmetric
      homodimer mimics a trans-autophosphorylation complex, and suggests that
      unphosphorylated PAK1 could dynamically adopt both the active and inactive
      conformations in solution.

PMID- 22153499
TI  - Extracellular complexes of the hematopoietic human and mouse CSF-1 receptor are
      driven by common assembly principles.
AB  - The hematopoietic colony stimulating factor-1 receptor (CSF-1R or FMS) is
      essential for the cellular repertoire of the mammalian immune system. Here, we
      report a structural and mechanistic consensus for the assembly of human and mouse
      CSF-1:CSF-1R complexes. The EM structure of the complete extracellular assembly
      of the human CSF-1:CSF-1R complex reveals how receptor dimerization by CSF-1
      invokes a ternary complex featuring extensive homotypic receptor contacts and
      striking structural plasticity at the extremities of the complex. Studies by
      small-angle X-ray scattering of unliganded hCSF-1R point to large domain
      rearrangements upon CSF-1 binding, and provide structural evidence for the
      relevance of receptor predimerization at the cell surface. Comparative structural
      and binding studies aiming to dissect the assembly principles of human and mouse
      CSF-1R complexes, including a quantification of the CSF-1/CSF-1R species cross
      reactivity, show that bivalent cytokine binding to receptor coupled to ensuing
      receptor-receptor interactions are common denominators in extracellular complex
      formation.

PMID- 22153500
TI  - Structure of hydrogenase maturation protein HypF with reaction intermediates
      shows two active sites.
AB  - [NiFe]-hydrogenases are multimeric proteins. The large subunit contains the
      NiFe(CN)(2)CO bimetallic active center and the small subunit contains Fe-S
      clusters. Biosynthesis and assembly of the NiFe(CN)(2)CO active center requires
      six Hyp accessory proteins. The synthesis of the CN(-) ligands is catalyzed by
      the combined actions of HypF and HypE using carbamoylphosphate as a substrate. We
      report the structure of Escherichia coli HypF(92-750) lacking the N-terminal
      acylphosphatase domain. HypF(92-750) comprises the novel Zn-finger domain, the
      nucleotide-binding YrdC-like domain, and the Kae1-like universal domain, also
      binding a nucleotide and a Zn(2+) ion. The two nucleotide-binding sites are
      sequestered in an internal cavity, facing each other and separated by ~14 A. The
      YrdC-like domain converts carbamoyl moiety to a carbamoyl adenylate intermediate,
      which is channeled to the Kae1-like domain. Mutations within either nucleotide
      binding site compromise hydrogenase maturation but do not affect the
      carbamoylphosphate phosphatase activity.

PMID- 22153501
TI  - Atomic-level protein structure refinement using fragment-guided molecular
      dynamics conformation sampling.
AB  - One of critical difficulties of molecular dynamics (MD) simulations in protein
      structure refinement is that the physics-based energy landscape lacks a middle
      range funnel to guide nonnative conformations toward near-native states. We
      propose to use the target model as a probe to identify fragmental analogs from
      PDB. The distance maps are then used to reshape the MD energy funnel. The
      protocol was tested on 181 benchmarking and 26 CASP targets. It was found that
      structure models of correct folds with TM-score >0.5 can be often pulled closer
      to native with higher GDT-HA score, but improvement for the models of incorrect
      folds (TM-score <0.5) are much less pronounced. These data indicate that template
      based fragmental distance maps essentially reshaped the MD energy landscape from
      golf-course-like to funnel-like ones in the successfully refined targets with a
      radius of TM-score ~0.5. These results demonstrate a new avenue to improve high
      resolution structures by combining knowledge-based template information with
      physics-based MD simulations.

PMID- 22153502
TI  - Galline Ex-FABP is an antibacterial siderocalin and a lysophosphatidic acid
      sensor functioning through dual ligand specificities.
AB  - Galline Ex-FABP was identified as another candidate antibacterial, catecholate
      siderophore binding lipocalin (siderocalin) based on structural parallels with
      the family archetype, mammalian Siderocalin. Binding assays show that Ex-FABP
      retains iron in a siderophore-dependent manner in both hypertrophic and
      dedifferentiated chondrocytes, where Ex-FABP expression is induced after
      treatment with proinflammatory agents, and specifically binds ferric complexes of
      enterobactin, parabactin, bacillibactin and, unexpectedly, monoglucosylated
      enterobactin, which does not bind to Siderocalin. Growth arrest assays
      functionally confirm the bacteriostatic effect of Ex-FABP in vitro under iron
      limiting conditions. The 1.8 A crystal structure of Ex-FABP explains the expanded
      specificity, but also surprisingly reveals an extended, multi-chambered cavity
      extending through the protein and encompassing two separate ligand specificities,
      one for bacterial siderophores (as in Siderocalin) at one end and one
      specifically binding copurified lysophosphatidic acid, a potent cell signaling
      molecule, at the other end, suggesting Ex-FABP employs dual functionalities to
      explain its diverse endogenous activities.

PMID- 22153503
TI  - Phosphorylation in protein-protein binding: effect on stability and function.
AB  - Posttranslational modifications offer a dynamic way to regulate protein activity,
      subcellular localization, and stability. Here we estimate the effect of
      phosphorylation on protein binding and function for different types of complexes
      from human proteome. We find that phosphorylation sites tend to be located on
      binding interfaces in heterooligomeric and weak transient homooligomeric
      complexes. Analysis of molecular mechanisms of phosphorylation shows that
      phosphorylation may modulate the strength of interactions directly on interfaces
      and that binding hotspots tend to be phosphorylated in heterooligomers. Although
      the majority of complexes do not show significant estimated stability differences
      upon phosphorylation or dephosphorylation, for about one-third of all complexes
      it causes relatively large changes in binding energy. We discuss the cases where
      phosphorylation mediates the complex formation and regulates the function. We
      show that phosphorylation sites are more likely to be evolutionary conserved than
      other interfacial residues.

PMID- 22153504
TI  - Crystallographic analysis of polypyrimidine tract-binding protein-Raver1
      interactions involved in regulation of alternative splicing.
AB  - The polypyrimidine tract-binding protein (PTB) is an important regulator of
      alternative splicing. PTB-regulated splicing of alpha-tropomyosin is enhanced by
      Raver1, a protein with four PTB-Raver1 interacting motifs (PRIs) that bind to the
      helical face of the second RNA recognition motif (RRM2) in PTB. We present the
      crystal structures of RRM2 in complex with PRI3 and PRI4 from Raver1, which-
      along with structure-based mutagenesis--reveal the molecular basis of their
      differential binding. High-affinity binding by Raver1 PRI3 involves shape-matched
      apolar contacts complemented by specific hydrogen bonds, a new variant of an
      established mode of peptide-RRM interaction. Our results refine the sequence of
      the PRI motif and place important structural constraints on functional models of
      PTB-Raver1 interactions. Our analysis indicates that the observed Raver1-PTB
      interaction is a general mode of binding that applies to Raver1 complexes with
      PTB paralogues such as nPTB and to complexes of Raver2 with PTB.

PMID- 22153505
TI  - Tandem SAM domain structure of human Caskin1: a presynaptic, self-assembling
      scaffold for CASK.
AB  - The synaptic scaffolding proteins CASK and Caskin1 are part of the fibrous mesh
      of proteins that organize the active zones of neural synapses. CASK binds to a
      region of Caskin1 called the CASK interaction domain (CID). Adjacent to the CID,
      Caskin1 contains two tandem sterile alpha motif (SAM) domains. Many SAM domains
      form polymers so they are good candidates for forming the fibrous structures seen
      in the active zone. We show here that the SAM domains of Caskin1 form a new type
      of SAM helical polymer. The Caskin1 polymer interface exhibits a remarkable
      segregation of charged residues, resulting in a high sensitivity to ionic
      strength in vitro. The Caskin1 polymers can be decorated with CASK proteins,
      illustrating how these proteins may work together to organize the cytomatrix in
      active zones.

PMID- 22153506
TI  - Structural and dynamic determinants of protein-peptide recognition.
AB  - Protein-peptide interactions play important roles in many cellular processes,
      including signal transduction, trafficking, and immune recognition. Protein
      conformational changes upon binding, an ill-defined peptide binding surface, and
      the large number of peptide degrees of freedom make the prediction of protein
      peptide interactions particularly challenging. To address these challenges, we
      perform rapid molecular dynamics simulations in order to examine the energetic
      and dynamic aspects of protein-peptide binding. We find that, in most cases, we
      recapitulate the native binding sites and native-like poses of protein-peptide
      complexes. Inclusion of electrostatic interactions in simulations significantly
      improves the prediction accuracy. Our results also highlight the importance of
      protein conformational flexibility, especially side-chain movement, which allows
      the peptide to optimize its conformation. Our findings not only demonstrate the
      importance of sufficient sampling of the protein and peptide conformations, but
      also reveal the possible effects of electrostatics and conformational flexibility
      on peptide recognition.

PMID- 22153507
TI  - Structure basis for the regulation of glyceraldehyde-3-phosphate dehydrogenase
      activity via the intrinsically disordered protein CP12.
AB  - The reversible formation of a glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      CP12-phosphoribulokinase (PRK) supramolecular complex, identified in oxygenic
      photosynthetic organisms, provides light-dependent Calvin cycle regulation in a
      coordinated manner. An intrinsically disordered protein (IDP) CP12 acts as a
      linker to sequentially bind GAPDH and PRK to downregulate both enzymes. Here, we
      report the crystal structures of the ternary GAPDH-CP12-NAD and binary GAPDH-NAD
      complexes from Synechococcus elongates. The GAPDH-CP12 complex structure reveals
      that the oxidized CP12 becomes partially structured upon GAPDH binding. The C
      terminus of CP12 is inserted into the active-site region of GAPDH, resulting in
      competitive inhibition of GAPDH. This study also provides insight into how the
      GAPDH-CP12 complex is dissociated by a high NADP(H)/NAD(H) ratio. An unexpected
      increase in negative charge potential that emerged upon CP12 binding highlights
      the biological function of CP12 in the sequential assembly of the supramolecular
      complex.

PMID- 22153508
TI  - The polydispersity of alphaB-crystallin is rationalized by an interconverting
      polyhedral architecture.
AB  - We report structural models for the most abundant oligomers populated by the
      polydisperse molecular chaperone alphaB-crystallin. Subunit connectivity is
      determined by using restraints obtained from nuclear magnetic resonance
      spectroscopy and mass spectrometry measurements, enabling the construction of
      various oligomeric models. These candidate structures are filtered according to
      their correspondence with ion-mobility spectrometry data and cross-validated by
      using electron microscopy. The ensuing best-fit structures reveal the polyhedral
      architecture of alphaB-crystallin oligomers, and provide a rationale for their
      polydispersity and facile interconversion.

PMID- 22153509
TI  - Structure analysis of the IL-5 ligand-receptor complex reveals a wrench-like
      architecture for IL-5Ralpha.
AB  - Interleukin-5 (IL-5) is the key mediator for the function of eosinophil
      granulocytes, whose deregulation is characteristic of hypereosinophilic diseases
      and presumably contributes to allergic asthma. IL-5 signaling involves two
      transmembrane receptors, IL-5Ralpha and the common beta chain, which upon
      formation of the ternary complex activate the JAK/STAT signaling cascade. To
      investigate the mechanism underlying ligand-receptor recognition, we determined
      the structure of IL-5 bound to the extracellular domain of IL-5Ralpha. IL-5 makes
      contact with all three fibronectin III-like domains of IL-5Ralpha, with the
      receptor architecture resembling a wrench. Mutagenesis data provide evidence that
      this wrench-like architecture is likely preformed. The structure demonstrates
      that for steric reasons, homodimeric IL-5 can bind only one receptor molecule,
      even though two equivalent receptor-binding sites exist. In regard to strong
      efforts being made to develop IL-5 antagonists for treating asthma and
      hypereosinophilic diseases, the advances in molecular understanding provided by
      this structure are of greatest value.

PMID- 22153510
TI  - Structure of a three-domain sesquiterpene synthase: a prospective target for
      advanced biofuels production.
AB  - The sesquiterpene bisabolene was recently identified as a biosynthetic precursor
      to bisabolane, an advanced biofuel with physicochemical properties similar to
      those of D2 diesel. High-titer microbial bisabolene production was achieved using
      Abies grandis alpha-bisabolene synthase (AgBIS). Here, we report the structure of
      AgBIS, a three-domain plant sesquiterpene synthase, crystallized in its apo form
      and bound to five different inhibitors. Structural and biochemical
      characterization of the AgBIS terpene synthase Class I active site leads us to
      propose a catalytic mechanism for the cyclization of farnesyl diphosphate into
      bisabolene via a bisabolyl cation intermediate. Further, we describe the
      nonfunctional AgBIS Class II active site whose high similarity to bifunctional
      diterpene synthases makes it an important link in understanding terpene synthase
      evolution. Practically, the AgBIS crystal structure is important in future
      protein engineering efforts to increase the microbial production of bisabolene.

PMID- 22153511
TI  - Structural conservation of the myoviridae phage tail sheath protein fold.
AB  - Bacteriophage phiKZ is a giant phage that infects Pseudomonas aeruginosa, a human
      pathogen. The phiKZ virion consists of a 1450 A diameter icosahedral head and a
      2000 A-long contractile tail. The structure of the whole virus was previously
      reported, showing that its tail organization in the extended state is similar to
      the well-studied Myovirus bacteriophage T4 tail. The crystal structure of a tail
      sheath protein fragment of phiKZ was determined to 2.4 A resolution. Furthermore,
      crystal structures of two prophage tail sheath proteins were determined to 1.9
      and 3.3 A resolution. Despite low sequence identity between these proteins, all
      of these structures have a similar fold. The crystal structure of the phiKZ tail
      sheath protein has been fitted into cryo-electron-microscopy reconstructions of
      the extended tail sheath and of a polysheath. The structural rearrangement of the
      phiKZ tail sheath contraction was found to be similar to that of phage T4.

PMID- 22153512
TI  - Probiotic yogurt consumption may improve gastrointestinal symptoms, productivity,
      and nutritional intake of people living with human immunodeficiency virus in
      Mwanza, Tanzania.
AB  - The gut-associated lymphoid tissue is a major site of human immunodeficiency
      virus (HIV) activity and significantly influences disease prognosis. Reducing
      immune activation due to gastroenteritis may thus help slow disease progression.
      Probiotic microorganisms have considerable immunomodulatory effects at the level
      of the gut-associated lymphoid tissue. A probiotic yogurt initiative was thus
      established in Mwanza, Tanzania, to improve gastrointestinal (GI) integrity and
      reduce the incidence and severity of opportunistic infections among people with
      HIV. The research objective was to retrospectively evaluate the effects of yogurt
      supplemented with Lactobacillus rhamnosus as an adjunct to the diet of people
      living with HIV on systemic and GI symptoms, daily routine activities, and
      nutritional intake. Eighty-five people with HIV consuming probiotic yogurt and 86
      controls were interviewed. Demographics and HIV disease stage were comparable
      between groups. Probiotic yogurt consumers reported an ability to work a median
      of 2 hours more daily (P = .01), experienced a lower fever incidence (P = .01),
      and were more likely to achieve daily nutrient requirements for vitamin A,
      several B complex vitamins, and calcium (P = .02). Antiretroviral users
      experienced less drug-induced stomach pain (P = .02) and a lower overall impact
      of GI symptoms on routine activities (P = .03). The results of this study need be
      further substantiated because of limits imposed by the observational,
      retrospective study design; however, results suggest that yogurt supplemented
      with L rhamnosus may effectively alleviate GI symptoms and improve productivity,
      nutritional intake, and tolerance to antiretroviral treatment among people with
      HIV in Mwanza.

PMID- 22153513
TI  - Short-term consumption of sucralose, a nonnutritive sweetener, is similar to
      water with regard to select markers of hunger signaling and short-term glucose
      homeostasis in women.
AB  - Nonnutritive sweeteners have been used to lower the energy density of foods with
      the intention of affecting weight loss or weight maintenance. However, some
      epidemiological and animal evidence indicates an association between weight gain
      or insulin resistance and artificial sweetener consumption. In the present study,
      we hypothesized that the nonnutritive sweetener sucralose, a trichlorinated
      sucrose molecule, would elicit responses similar to water but different from
      sucrose and sucrose combined with sucralose on subjective and hormonal
      indications of hunger and short-term glucose homeostasis. Eight female volunteers
      (body mass index, 22.16 +/- 1.71 kg/m(2); age, 21.75 +/- 2.25 years) consumed
      sucrose and/or sucralose in water in a factorial design. Blood samples were taken
      at fasting and 30 and 60 minutes after treatment followed by a standardized
      breakfast across treatments, and blood samples were taken 30, 60, 90, and 120
      minutes after breakfast. Plasma was analyzed for glucose, insulin, glucagon,
      triacylglycerols (TAG), and acylated ghrelin. Perceptions of hunger and other
      subjective measurements were assessed before each blood sample. No differences
      were detected in subjective responses, circulating triacylglycerol, or glucagon
      concentrations among treatments over time. Significant differences were observed
      in insulin, glucose, and acylated ghrelin concentrations over time only between
      sucrose-containing treatments and non-sucrose-containing treatments regardless of
      sucralose consumption. Therefore, sucralose may be a relatively inert
      nonnutritive sweetener with regard to hunger signaling and short-term glucose
      homeostasis.

PMID- 22153514
TI  - Fortification of flours with folic acid reduces homocysteine levels in Brazilian
      women.
AB  - Our hypothesis is that the fortification of flour with folic acid contributes to
      the reduction of plasma homocysteine (Hcy). We conducted a cross-sectional study
      covering 2 periods, before and after fortification (2002-2003 and 2008-2009,
      respectively), to assess the influence of the consumption of corn and wheat
      flours prefortification and postfortification with folic acid on Hcy levels and
      other biomarkers. In the total, 93 women (38 prefortification and 55
      postfortification) were included. Levels of lipids and glucose, total Hcy and
      serum folate, and cobalamin were determined using commercial kits by colorimetric
      method, competitive immunoassay, and chemiluminescence, respectively The
      participants' average age was 48.1 +/- 9.5 years for the prefortification group
      and 39.1 +/- 4.1 years for the postfortification group (P < .001) but adjusted
      statistical tests by age. Both groups presented obesity class 1. In the
      prefortification group, 71.1% (n = 27) of women had a dietary intake of folate,
      which was lower than the current recommended for adults (< 400 MUg/d), whereas in
      the postfortification group, only 16.4% (n = 9) of women had lower intakes than
      recommended. In the prefortification group, 42.1% (n = 16) of women had
      hyperhomocysteinemia (> 10 mmol/L) compared with only 9.1% (n = 5) in the
      postfortification group. Moreover, statistically significant differences were
      found between the 2 groups in total cholesterol, high-density lipoprotein,
      triglycerides, and dietary fiber. Our findings corroborate the hypothesis that
      fortification of wheat and corn flours with folic acid can possibly be associated
      with lower concentrations of plasma Hcy, providing probable greater
      cardiovascular protection in this group.

PMID- 22153515
TI  - Purple sweet potato anthocyanins attenuate hepatic lipid accumulation through
      activating adenosine monophosphate-activated protein kinase in human HepG2 cells
      and obese mice.
AB  - Purple sweet potato is a functional food rich in anthocyanins that possess
      disease-preventive properties. Anthocyanins are known to possess potent
      antidiabetic properties. However, the effect of the anthocyanin fraction (AF)
      from purple sweet potato on hepatic lipid metabolism remains unclear. Our
      hypothesis is that AF inhibits hepatic lipid accumulation through the activation
      of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways in
      vitro and in vivo. In this study, we evaluated body weight, liver histology, and
      hepatic lipid content in high-fat diet (HFD)-fed ICR mice treated with AF. In
      addition, we characterized the underlying mechanism of AF's effects in HepG2
      hepatocytes through Western blot analysis. Anthocyanin fraction (200 mg/kg per
      day) reduced weight gain and hepatic triglyceride accumulation and improved serum
      lipid parameters in mice fed an HFD for 4 weeks. Anthocyanin fraction
      significantly increased the phosphorylation of AMPK and acetyl-coenzyme A
      carboxylase (ACC) in the liver and HepG2 hepatocytes. In addition, AF down
      regulated the levels of sterol regulatory element-binding protein 1 and its
      target genes including ACC and fatty acid synthase (FAS). The specific AMPK
      inhibitor compound C attenuated the effects of AF on the expression of lipid
      metabolism-related proteins such as SREBP-1 and FAS in HepG2 hepatocytes. The
      beneficial effects of AF on HFD-induced hepatic lipid accumulation are thus
      mediated through AMPK signaling pathways, suggesting a potential target for the
      prevention of obesity.

PMID- 22153516
TI  - Prostaglandin E2 production in mice is reduced by consumption of range-fed
      sources of red meat.
AB  - Many view bison as a healthful alternative to other red meat sources, and as a
      way to decrease health risks, they associate it with meat consumption. Using mice
      as a model for immune function, we hypothesized that consumption of meat from
      range-fed bison would decrease prostaglandin (PG) E2 and alter prostacyclin
      (PGI2) release upon immune challenge when compared with mice fed meat from grain
      finished bison, range-fed beef, feedlot steers, free-ranging elk, or chicken
      breast. After 2 weeks on an experimental diet and inflammatory stimulation, mouse
      peritoneal macrophage was isolated and analyzed in 12 animals per diet.
      Peritoneal cell arachidonic acid increased in response to a chicken-based diet (P
      < .05), which was likely attributable to higher arachidonic acid intake. Release
      of PGE2 was lowest in mice consuming meat of range-fed beef, range-fed bison, and
      elk but was highest with meat of grain-finished beef and intermediate in mice fed
      chicken (P < .05). Mice fed elk meat had the greatest PGI2, whereas PGI2 was
      decreased in mice fed meat of either range bison, range beef, or chicken (P <
      .05) and intermediate in mice fed meat of steers or bison finished in a feedlot.
      We conclude that consumption of meats characteristic of range-fed ruminants or
      wild ungulates supports reduced PGE2 and greater PGI2 synthesis, indicating
      potentially greater immune health and lower blood clotting potential than meat
      from grain-finished cattle or bison in this model system.

PMID- 22153518
TI  - Soy protein supports cardiovascular health by downregulating
      hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding
      protein-2 and increasing antioxidant enzyme activity in rats with dextran sodium
      sulfate-induced mild systemic inflammation.
AB  - Animal and human studies have indicated that the presence of soy in the diet
      improves cardiovascular health. Inflammation plays a pivotal role in the
      progression of cardiovascular disease (CVD). However, little is known about how
      dextran sodium sulfate (DSS)-induced systemic inflammation impacts overall heart
      health and, correspondingly, how soy protein modulates risk of CVD development in
      DSS-induced systemic inflammation. We hypothesized that soy protein-fed rats
      would have a lower risk of CVD by beneficial alteration of gene expression
      involving lipid metabolism and antioxidant capacity in DSS-induced systemic
      inflammation. Forty Sprague-Dawley rats were divided into 4 groups: casein,
      casein + DSS, soy protein, and soy protein + DSS. After 26 days, inflammation was
      induced in one group from each diet by incorporating 3% DSS in drinking water for
      48 hours. Soy protein-fed rats had lower final body weights (P = .010),
      epididymal fat weights (P = .049), total cholesterol (P < .001), and low-density
      lipoprotein cholesterol (P < .001). In regard to gene expression, soy protein-fed
      rats had lower sterol regulatory element-binding protein-2 (P = .032) and
      hydroxymethylglutaryl-coenzyme A reductase (P = .028) levels and higher low
      density lipoprotein receptor levels (P = .036). Antioxidant enzyme activity of
      superoxide dismutase and catalase was higher among the soy protein groups (P =
      .037 and P = .002, respectively). These results suggest that soy protein
      positively influences cardiovascular health by regulating serum lipids through
      modified expression of sterol regulatory element-binding protein-2 and its
      downstream genes (ie, hydroxymethylglutaryl-coenzyme A reductase and low-density
      lipoprotein receptor) and by promoting the antioxidant enzyme activity of
      superoxide dismutase and catalase.

PMID- 22153517
TI  - Diet-induced obesity leads to decreased hepatic iron storage in mice.
AB  - An increased risk of iron deficiency has been reported in obese individuals. We
      investigated hepatic iron status and serum levels of both adipokines and
      inflammatory markers in obese mice to test the hypothesis that high-fat-diet
      (HFD)-induced obesity leads to reduced iron storage associated with inflammation.
      Four-week-old C57BL mice were fed a HFD containing 60% energy from fat for 16
      weeks and were compared with mice on a control diet with 10% energy from fat. The
      HFD group had significantly higher levels of leptin (43.7 ng/mL in control, n =
      16 vs 104.3 ng/mL in HFD, n = 17; P < .001) and significantly lower amounts of
      high-molecular-weight adiponectin (4.80 MUg/mL in control, n = 16 vs 3.67 MUg/mL
      in HFD, n = 18; P = .002) compared with the control group. Higher serum amyloid A
      levels in the HFD group (60.4 MUg/mL in control, n = 17 vs 117.9 MUg/mL in HFD, n
      = 18; P < .001) suggest inflammation in the HFD-induced obese animals. The HFD
      group had lower hepatic nonheme iron (3.12 MUg/mg protein in control, n = 17 vs
      0.869 MUg/mg protein in HFD, n = 16; P < .001). Expression of hepcidin messenger
      RNA (mRNA) was only 54% of the control levels in HFD mice (P = .016). However,
      the ratio of hepcidin mRNA expression to nonheme iron was 2.5-fold higher in the
      HFD compared with the control animals. Hepcidin is a homeostatic regulator of
      iron metabolism that restricts intestinal iron absorption and is also known as a
      mediator of inflammation. Increased serum amyloid A levels and a higher ratio of
      hepatic hepcidin mRNA expression to nonheme iron suggest that lower hepatic iron
      status in obese animals might be associated with inflammation.

PMID- 22153519
TI  - Menhaden oil administration to dogs treated with radiation for nasal tumors
      demonstrates lower levels of tissue eicosanoids.
AB  - Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or menhaden oil may
      reduce inflammatory eicosanoids (prostaglandin E2, thromboxane B2, leukotriene
      B4, and 11-dehydro thromboxane B2), matrix metalloproteinases (MMPs), and blood
      lactate in dogs with nasal carcinomas receiving radiation therapy. We
      hypothesized that menhaden oil would reduce inflammation from radiation damage
      and lower blood lactate levels in dogs with nasal carcinoma. In a randomized,
      double-blind, placebo-controlled clinical study, 12 dogs with malignant
      carcinomas of the nasal cavity were given dietary menhaden oil (DHA and EPA) or
      soybean oil (control) and then received radiation therapy. Megavoltage radiation
      was delivered in 18 fractions to a total dose of 56 Gy. Blood levels of DHA, EPA,
      insulin, glucose, lactic acid, and MMPs 2 and 9; resting energy expenditure; and
      inflammatory eicosanoids from nasal biopsies were measured throughout radiation
      therapy. Samples were obtained from each patient 1 week before the start of
      radiation therapy, at start of radiation, and 7, 18 (end of radiation therapy),
      and 42 days after radiation was initiated. Dogs that are fed with menhaden oil
      had significantly (P < .05) higher plasma concentration of DHA by 500% and EPA by
      200% and had significantly lower tissue inflammatory eicosanoids and decreased
      resting energy expenditure by 20% when compared with controls. Increased plasma
      DHA was significantly associated (P < .05) with decreased plasma lactic acid and
      MMPs. These data may suggest that dietary fish oil could reduce some detrimental
      inflammatory eicosanoids and metabolic consequences of radiation therapy.

PMID- 22153520
TI  - Silk protein hydrolysate increases glucose uptake through up-regulation of GLUT 4
      and reduces the expression of leptin in 3T3-L1 fibroblast.
AB  - The purpose of our research was to test the hypothesis that silk protein
      hydrolysate increases glucose uptake in cultured murine embryonic fibroblasts.
      Insulin sensitizing activity was observed in a cell-based glucose uptake assay
      using 3T3-L1 embryonic fibroblasts. The treatment of 1 mg/mL of silk peptide E5K6
      plus 0.2 nM insulin was associated with a significant increase in glucose uptake
      (124.0% +/- 2.5%) compared to treatment with 0.2 nM insulin alone. When the 3T3
      L1 cells were induced to differentiate into fibroblasts, fat droplets formed
      inside the cells. Silk peptide E5K6 reduced the formation of fat droplets at the
      1-mg/mL dosage (86.1% +/- 2.5%) when compared to the control (100.0% +/- 5.8%). A
      1 mg/mL dose of silk peptide E5K6 significantly increased GLUT 4 expression
      (131.5% +/- 4.0%). The treatment of 1 mg/mL of silk peptide E5K6 did not present
      any changes for adipogenic expressed genes, but leptin expression was
      significantly increased by silk peptide E5K6 supplementation (175.9% +/- 11.1%).
      From these results, silk peptide E5K6 increased glucose uptake via up-regulation
      of GLUT 4 and decreased fat accumulation via the up-regulation of leptin.

PMID- 22153521
TI  - Quantitative high-resolution transmission electron microscopy of single atoms.
AB  - Single atoms can be considered as the most basic objects for electron microscopy
      to test the microscope performance and basic concepts for modeling image
      contrast. In this work high-resolution transmission electron microscopy was
      applied to image single platinum, molybdenum, and titanium atoms in an aberration
      corrected transmission electron microscope. The atoms are deposited on a self
      assembled monolayer substrate that induces only negligible contrast. Single-atom
      contrast simulations were performed on the basis of Weickenmeier-Kohl and Doyle
      Turner form factors. Experimental and simulated image intensities are in
      quantitative agreement on an absolute intensity scale, which is provided by the
      vacuum image intensity. This demonstrates that direct testing of basic properties
      such as form factors becomes feasible.

PMID- 22153522
TI  - New drugs for thromboprophylaxis in atrial fibrillation.

PMID- 22153523
TI  - Developing strategies to improve the quality of life of patients with gluten
      intolerance in patients with and without coeliac disease.

PMID- 22153524
TI  - Non-dietary therapeutic clinical trials in coeliac disease.
AB  - Coeliac disease is a permanent immunological intolerance to gluten proteins in
      genetically predisposed individuals. The only management is life-long strict
      adherence to a gluten-free diet. Unfortunately, compliance with gluten-free diet
      is very difficult in practice due to the widespread presence of gluten in Western
      diets. For this reason, about 50% of coeliacs following a gluten-free diet
      continue to suffer from symptoms and present with autoantibodies and/or villous
      atrophy while on a gluten-free diet. It is therefore important to explore new
      therapies to improve the management of coeliac disease. To date, five
      experimental therapies have been tested in randomized and controlled clinical
      trials. Larazotide acetate reduces the para-cellular passage of gluten to the
      lamina propria by preventing the opening of intercellular tight junctions. The
      endopeptidases ALV003 and AN-PEP break down gluten to produce less or non-toxic
      peptide fragments. A therapeutic vaccine is being tested with the aim of
      developing gluten tolerance. Finally, infection with the nematode Necator
      americanus and treatment with the CCR9 antagonist Traficet-EN have also been
      reported. While substantial progress has been made in the last few years, it is
      important to remember that all these investigational therapies are in research
      stage and are generally being considered as "adjunctive" therapies to the gluten
      free diet and not as substitutes of the gluten-free diet at this point in time.

PMID- 22153525
TI  - Consumption of cocoa, tea and coffee and risk of cardiovascular disease.
AB  - Daily intake of an anti-thrombotic diet may offer a suitable and effective way of
      coronary artery disease (CAD) prevention. A diet rich in fruit, vegetables,
      complex carbohydrates, monounsaturated fat and fish, moderate alcohol consumption
      but poor in salt, saturated fat and simple sugars, plays an important role in
      protect against CAD. Chocolate, coffee and tea, unfairly not included in
      "traditional healthy food basket", have received much attention over the past few
      years, if for no other reason than they are consumed worldwide and are important
      dietary sources of polyphenols (flavonols and cathechins). Several in vitro and
      in vivo studies have tried to elucidate the role of these foods and a large
      amount of experimental studies clearly indicated a beneficial effect of
      polyphenols in influencing CAD. However, data from epidemiological studies are
      not conclusive. The blood pressure lowering effects and the anti-inflammatory
      activity of dark chocolate suggests its use as potential prophylactic and
      therapeutic agent, in particular considering that epidemiological studies suggest
      that dark chocolate is inversely associated with CAD. Although regular
      consumption of moderate quantities of coffee and (green) tea seems to be
      associated with a small protection against CAD, results from randomized clinical
      trials about their beneficial effects are less evident. As for other diffuse
      consumption habits, such as that of alcohol, moderation is the key word. In fact,
      both for coffee and chocolate, the optimal healthy effects on CAD have been
      observed to be associated with a moderate intake, while healthy outcomes vanish
      at heavy consumption.

PMID- 22153526
TI  - Urticaria and its subtypes: the role of second-generation antihistamines.
AB  - Urticaria is a heterogeneous group of debilitating skin disorders characterized
      by wheals, pruritus, and frequently angioedema. The various forms of urticaria
      are often chronic and can exact a toll on quality of life. New diagnostic
      criteria and management guidelines are available to assist primary care
      physicians in the identification and proper treatment of different subtypes of
      urticaria. Second-generation antihistamines are recommended as first-line therapy
      because of their high degree of efficacy and safety. It is important to note,
      however, that European indications for most agents in this class are limited to
      specific forms of urticaria. The exception is desloratadine, the only second
      generation antihistamine approved for the treatment of all urticaria subtypes in
      the European Union. Guidelines and best practice suggest that doses of
      antihistamines up to 4 times higher than those normally recommended for urticaria
      may benefit patients who do not respond to standard doses of antihistamines.
      Adjunctive therapy with leukotriene receptor antagonists may be advantageous in
      certain subgroups of patients who have suboptimal responses to antihistamine
      monotherapy. In all cases, physicians should work closely with patients to ensure
      proper adherence to prescribed regimens-a component that is often lacking but
      holds the key to successful outcomes.

PMID- 22153527
TI  - The autumn of acupuncture.

PMID- 22153528
TI  - Should a radiological diagnosis of hepatocellular carcinoma be routinely
      confirmed by a biopsy? Yes.
AB  - Hepatocellular carcinoma (HCC) represents approximately 85 to 90% of all primary
      liver cancers (PLC) and every year, more than 560,000 people are diagnosed as
      affected by this cancer. The identification of risk factors for HCC prompted the
      creation of screening and surveillance programs in patients affected by chronic
      liver diseases with the aim of detecting HCC nodules as soon as possible and
      provide effective and hopefully curative therapy A correct diagnosis is of
      paramount importance for the surveillance program as well as for the choice of
      the appropriate therapy. Both in the diagnosis of small HCC and in the choice of
      the therapy for locally advanced HCC the diagnosis must be certain. Improvements
      of the radiological imagine techniques have surely enhanced both early diagnosis
      and tumor staging, allowing a reasonably accurate diagnosis, but cannot provide
      the certainty that in clinical practice is essential for an adequate workout.
      Therefore, the histopatological definition of the tumor is imperative both for an
      appropriate therapy and for an accurate prognostic evaluation.

PMID- 22153529
TI  - Should a radiological diagnosis of hepatocellular carcinoma be routinely
      confirmed by a biopsy? No.
AB  - Modern multiphase diagnostic imaging allows diagnosis of hepatocellular carcinoma
      with high specificity in a large proportion of cases. Additional aspects of tumor
      biology also can be evaluated noninvasively through observation of tumor behavior
      (growth rate, satellites, vascular invasion) and other indicators of tumor
      biology (avid uptake of fluorodeoxyglucose, high circulating levels of tumor
      markers such as alphafetoprotein). Routinely requiring biopsy confirmation for
      diagnosis of HCC exposes many patients to unnecessary risk, may delay diagnosis,
      and in some cases leads to withholding of potentially beneficial treatment.
      Biopsy for assessment of tumor molecular markers is promising but remains
      investigational. When diagnosis of HCC is clinically evident by imaging criteria,
      tumor biopsy should not be required prior to initiating treatment.

PMID- 22153530
TI  - Risk of venous thromboembolism in first- and second-generation immigrants in
      Sweden.
AB  - BACKGROUND: There are ethnic differences in the incidence of venous
      thromboembolism. This is the first nationwide study to examine whether there is
      an association between country of birth in first-generation immigrants and first
      hospitalisation for venous thrombosis (VT) and pulmonary embolism (PE), and to
      study whether a similar association exists in second-generation immigrants.
      METHODS: The study is a nationwide follow-up study. The study subjects were first
      and second-generation immigrants residing in Sweden between January 1, 1964 and
      December 31, 2007. The reference population comprised first- and second
      generation Swedish-born individuals. Standardised incidence ratios (SIRs) for VT
      and PE, standardised with regard to age, geographic region of residence, time
      period, and socioeconomic status, were estimated by sex in first- and second
      generation immigrants. RESULTS: First-generation male and/or female immigrants
      from Greece, Italy, Spain, Finland, Baltic countries, Central Europe, Eastern
      Europe, Russia, Latin America, Turkey, Iran, and Iraq had a lower risk of VT
      and/or PE than Swedish-born individuals. The lower risk of VT and/or PE in some
      first-generation immigrant groups was not replicated in the second generation.
      However, in certain second-generation immigrant groups, the risk of VT/PE was
      similar to that in the corresponding parental groups. CONCLUSIONS: Country of
      birth affects the risk of VT and PE in several immigrant groups. Our study
      indicates that ethnicity-related inherited and acquired venous thromboembolism
      risk factors play a role in the aetiology of venous thromboembolism. Ethnic
      differences in thromboembolism risk even exist in Caucasian European populations,
      and may thus be important to consider in genetic studies.

PMID- 22153531
TI  - Modified clopidogrel loading dose according to platelet reactivity monitoring in
      patients carrying ABCB1 variant alleles in patients with clopidogrel resistance.
AB  - OBJECTIVES: The aim of the present study was to investigate the impact of a
      adjusted clopidogrel loading dose (LD) according to platelet reactivity index in
      carriers of ABCB1 mutant allele undergoing percutaneous coronary intervention
      (PCI). METHODS: All patients met the inclusion criteria were recruited in the
      present study. Platelet reactivity was measured using the vasodilator-stimulated
      phosphoprotein (VASP) index. High treatment platelet reactivity (HTPR) was
      determined by a cut-off value of >50%. The genetic polymorphism of ABCB1 was
      determined by allele-specific polymerase chain reaction (PCR). In patients
      carrying ABCB1 and HTPR after a first 300-mg LD of clopidogrel, dose adjustment
      was performed by using up to 3 additional 300-mg LDs to obtain a VASP index<50%.
      The rate of major adverse cardiovascular events (MACE) and major or minor
      bleeding in one month were recorded. RESULTS: 536 patients were included in the
      present study. One hundred seventy-two patients (32%) carried ABCB1 mutant allele
      (11 homozygotes [2%] and 161 heterozygotes [30%]). The VASP index in these
      patients was significantly higher than in homozygotic patients for the wild
      allele (65.5+/-13.8% vs. 47.6+/-21.8%; p<0.001). Of the 172 ABCB1 mutant allele
      carriers, 130 were considered to have HTPR. After a second clopidogrel LD, the
      VASP index was significantly decreased in these patients (66.9+/-12.8% vs.50.2+/
      18.3%; <0.001). Finally, dose adjustment according to platelet reactivity
      monitoring enabled 88% of ABCB1 mutant allele carriers and 91% of wild allele
      carriers exhibiting HTPR to reach a VASP index<50%. The rate of MACE and major or
      minor bleeding in one-month follow-up between the wild allele carriers and the
      mutant allele carriers didn't differentiate significantly. CONCLUSIONS: Increased
      and adjusted clopidogrel loading dose according to platelet reactivity monitoring
      attenuated clopidogrel resistance in carriers of ABCB1 mutant allele.

PMID- 22153532
TI  - Ascorbic acid prevents vascular dysfunction induced by oral glucose load in
      healthy subjects.
AB  - OBJECTIVES: To examine the effects of oral glucose load on forearm circulatory
      regulation before and after ascorbic acid administration in healthy subjects.
      DESIGN: Microcirculation study with laser Doppler was performed at the hand in
      basal conditions, after ischemia and after acetylcholine and nitroprusside;
      strain gauge plethysmography was performed at basal and after ischemia. The tests
      were repeated in the same sequence 2 hour after oral administration of glucose
      (75 g). The subjects were randomised for administration of ascorbic acid (1 g
      bid) or placebo (sodium bicarbonate 1 g bid) for 10 days. After that, the tests
      were repeated before and after a new oral glucose load. Blood pressure and heart
      rate were monitored. RESULTS: Macrocirculatory flux, pressure values and heart
      rate were unvaried throughout the study. The glucose load caused a reduction in
      the hyperemic peak flow with laser Doppler and plethysmography; it reduced flux
      recovery time and hyperemic curve area after ischemia; acetylcholine elicited a
      minor increase in flux with laser Doppler. The response to nitroprusside was
      unvaried after glucose load as compared to basal conditions. Treatment with
      ascorbic acid prevented the decrease in hyperemia after glucose, detected with
      laser Doppler and plethysmography. Ascorbic acid prevented the decreased response
      to acetylcholine after glucose, the response to nitroprusside was unaffected by
      ascorbic acid. Results after placebo were unvaried. CONCLUSIONS: Oral glucose
      load impairs endothelium dependent dilation and hyperaemia at microcirculation,
      probably via oxidative stress; ascorbic acid can prevent it.

PMID- 22153533
TI  - Serum hyaluronic acid and laminin as potential tumor markers for upper
      gastrointestinal cancers.
AB  - BACKGROUND: Early diagnosis of patients with upper gastrointestinal cancer is
      important because many cases are diagnosed in advanced stages and have poor
      prognosis. Several studies have reported increased serum levels of hyaluronic
      acid and laminin in various cancers and the correlation of the levels with poor
      prognosis. However, little data on the use of serum hyaluronic acid and laminin
      levels for early detection of esophageal and gastric cancers are available.
      METHODS: We assessed serum hyaluronic acid and laminin levels using enzyme-linked
      immunosorbent assay in 20 gastric cardia cancer, 23 gastric noncardia cancer and
      20 esophageal squamous cell carcinoma incident cases and 25 controls in the
      Golestan Province, northern Iran, a high risk area for upper gastrointestinal
      cancers. RESULTS: Mean serum hyaluronic acid and laminin concentrations in cancer
      cases were higher than in controls in crude analyses. Significant correlations
      were observed between hyaluronic acid levels and gastric noncardia cancer (Beta
      coefficient=0.390; P=0.01) and esophageal squamous cell carcinoma (Beta
      coefficient=0.332; P=0.05) and between laminin levels and gastric cardia cancer
      (Beta-coefficient=0.454; P=0.003) in multivariate models. For esophageal squamous
      cell carcinoma, gastric cardia cancer, and gastric noncardia cancer, area under
      ROC curve (AUC) of hyaluronic acid was 0.708, 0.694, and 0.770, and of laminin
      was 0.706, 0.828, and 0.671. CONCLUSIONS: Our study suggests that hyaluronic acid
      and laminin may be used to identify potentially high-risk groups of upper
      gastrointestinal cancers for further diagnostic work-ups, particularly in high
      incidence areas. Nevertheless, further studies with larger sample size and tumor
      staging information are warranted to clarify the clinical significance of
      hyaluronic acid and laminin in those cancers.

PMID- 22153535
TI  - How to save costs by reducing unnecessary testing: lean thinking in clinical
      practice.
AB  - BACKGROUND: The burden of health care expenditure on national budgets has
      increased dramatically over the past decade. A pilot study in our hospital
      demonstrated that many unnecessary diagnostic tests were performed routinely. The
      aim of this study was to reduce the costs of unnecessary diagnostic tests.
      METHODS: All diagnostic costs between 2006 and 2008 of the internal medicine
      department of the VU University Centre were evaluated. A target was set to reduce
      diagnostic expenditure by 7.5% in 2009 compared to 2008. A few interventions were
      introduced including introducing posters and pocket cards detailing the costs of
      diagnostic tests, six weekly feedback on diagnostics costs, mentorship of junior
      doctors, unbundling panel tests and increasing protocol adherence. Main outcome
      measures were the reduction in the total diagnostic costs and the total number of
      laboratory tests performed in the internal medicine department in 2009. RESULTS:
      In 2009, we achieved a 13% reduction in the total diagnostic costs compared to
      2008. The department of internal medicine spent 2.80 million euro and 2.45
      million euro on the diagnostic tests in 2008 and 2009 respectively and thereby
      saved 350.000 euro in 2009. The largest reduction was achieved by reducing the
      number of laboratory tests performed. CONCLUSION: Introduction of a few simple
      measures to improve awareness among the physicians led to a significant reduction
      in the diagnostic costs in the department of internal medicine. Extending these
      measures to the entire hospital and even entire country will in our opinion lead
      to significant reduction in the health care costs.

PMID- 22153534
TI  - The obesity gene and colorectal cancer risk: a population study in Northern
      Italy.
AB  - BACKGROUND: Representing the second cause of cancer-related death after lung
      cancer in men and breast cancer in women, colorectal cancer (CRC) is a major
      health problem in Italy. Obesity is reckoned to favor CRC; however, the
      underlying mechanisms are unclear. Recently, a single nucleotide polymorphism
      (SNP) in the fat mass and obesity associated (FTO) gene was found to be
      significantly associated with obesity. AIMS: To establish whether the FTO SNP
      rs9939609 may represent a risk factor for CRC and adenoma in the Italian
      population. PATIENTS AND METHODS: 1,037 subjects were enrolled in the study and
      divided in 3 groups: CRC (341 pts., M/F=197/144, mean age=65.17+/-11.16 years),
      colorectal adenoma (385 pts., M/F=247/138, mean age=62.49+/-13.01 years), healthy
      controls (311 pts., M/F=150/161, mean age=57.31+/-13.84 years). DNA was extracted
      from whole blood, and stored frozen for rs9939609 genotyping by real-time PCR.
      RESULTS: The frequency of the obesity-associated mutated A allele (AA+AT) on the
      FTO gene was 69.77% among controls, and 71.85% and 65.71% respectively among CRC
      and polyp patients. Compared to control subjects the AA+AT genotype had no
      significant effect on the risk for either CRC (OR=1.106; CI 95%=0.788-1.550;
      p=0.561) or colorectal adenomas (OR=0.830; CI 95%=0.602-1.144; p=0.255). We did
      not observe any association between the AA genotype and CRC/polyp localization
      and age at diagnosis. As measured in a patient subset, carriership of the risk
      alleles did not reflect in a significantly altered BMI. CONCLUSION: The obesity
      linked FTO variants do not play a significant role in modulating the colorectal
      cancer risk in the Italian population.

PMID- 22153536
TI  - Age- and gender-specific association between intraocular pressure and metabolic
      variables in a Taiwanese population.
AB  - BACKGROUND: To analyze the relationship between intraocular pressure, metabolic
      variables, and components of metabolic syndrome in different age and gender
      groups. METHODS: We examined 10,491 Taiwanese adults aged 21 to 79 years and
      categorized according to gender and age. All participants underwent examinations,
      including body mass index (BMI), waist circumference, blood pressure, intraocular
      pressure, and blood chemistry. Multiple linear regression analyses were performed
      to evaluate the relationships between intraocular pressure and these variables as
      well as to determine the relative influence of each component of metabolic
      syndrome. RESULTS: Intraocular pressure showed a significant reduction with aging
      in men but not in women. BMI had a positive association with intraocular pressure
      in young adults and middle-aged men. Systolic blood pressure was positively
      associated with intraocular pressure in most groups, whereas diastolic blood
      pressure was positively associated with intraocular pressure only in middle-aged
      and elderly men. Fasting blood sugar levels showed a significant association with
      high intraocular pressure in middle-aged and elderly adults. All participants
      with metabolic syndrome had higher intraocular pressure levels, and each
      component of metabolic syndrome had a distinct effect on the intraocular
      pressure, with blood pressure being the strongest predictor. CONCLUSION: Elevated
      intraocular pressure is associated with a number of metabolic variables, and each
      component of metabolic syndrome has a distinct impact on the intraocular pressure
      in individual age- and gender-specific groups. The present results may allow
      internal medicine specialists to manage metabolic risk factors while considering
      possible ocular involvement and potential treatment interactions.

PMID- 22153537
TI  - Traditional and novel cardiovascular risk factors in non-functioning adrenal
      adenomas.
AB  - BACKGROUND: The majority of the incidentally discovered adrenal masses are non
      functioning adrenal adenomas; however data regarding traditional and novel
      cardiovascular risk predictors in these subjects is lacking. The objective of our
      study was to investigate the levels of PAI-1, IL-6 and Apelin along with several
      traditional cardiovascular risk markers in subjects with non-functioning adrenal
      adenomas. METHODS: 38 subjects with non-functioning adrenal adenomas and 30, age,
      gender and BMI matched healthy controls were enrolled. Participants underwent
      hormonal evaluation including morning cortisol, adrenocorticotrophic hormone
      (ACTH), post dexamethasone suppression test (DST) cortisol,
      dehydroepiandrosterone sulfate (DHEAS) and urinary cortisol. Anthropometric and
      metabolic parameters, body composition, PAI-1, IL-6 and Apelin were measured.
      RESULTS: Subjects with non-functioning adrenal adenomas had significant
      elevations in systolic blood pressure, mean arterial pressure, waist
      circumference, uric acid, and post DST cortisol and had significantly reduced
      levels of DHEAS when compared to BMI matched controls. No significant difference
      was observed in terms of PAI-1, IL-6 and Apelin between groups. PAI-1 and IL-6
      were significantly correlated with mean arterial pressure, BMI, uric acid, total
      and LDL-cholesterol. Linear regression analysis showed that morning cortisol and
      Apelin levels independently predicted HOMA levels in subjects with adrenal
      adenomas. CONCLUSION: Subjects with non-functioning adrenal adenomas feature
      several cardiovascular risk factors even when compared to BMI matched
      individuals. Subtle cortisol autonomy in adrenal adenomas may be associated with
      those findings.

PMID- 22153538
TI  - Vitamin D status in primary hyperparathyroidism.
AB  - BACKGROUND: Hypovitaminosis D worsens the manifestations of primary
      hyperparathyroidism (PHPT). Only a few studies have assessed the status of
      vitamin D in PHPT. The objective of this study was to determine the prevalence of
      25(OH)D levels<50 nmol/L in PHPT in comparison to a population without PHPT.
      METHODS: Subjects with PHPT were identified from the computerized database of the
      Clalit Health Services in Israel and were included only if they had an available
      serum 25(OH)D test result in 2009 and were not taking vitamin D supplements in
      2008-2009 prior to the 25(OH)D test result. Subjects with renal failure were
      excluded (included n=1180). All other subjects with an available 25(OH)D value in
      2009 constituted the control group (n=184,479). RESULTS: Subjects with PHPT and
      25(OH)D<50 nmol/L had higher levels of serum PTH, alkaline phosphatase, and
      calcium levels compared to those with 25(OH)D levels>=50 nmol/L (P<0.02). The
      mean serum 25(OH)D level was 47.7+/-22.5 nmol/L compared to 52.1+/-24.5 nmol/L in
      the control group (P<0.001). 59.6% of subjects with PHPT had 25(OH)D levels<50
      nmol/L as compared to 49.5% in the control group (P<0.001). Logistic regression,
      controlling for gender, ethnicity, age, and seasonality, showed that PHPT
      independently predicted 25(OH)D levels<50 nmol/L; OR=1.61(95% CI, 1.43-1.82).
      CONCLUSIONS: Serum 25(OH)D levels<50 nmol/L are frequent in PHPT, are more common
      than in controls, and are associated with more severe bone disease based on
      higher serum PTH and bone turnover biomarkers.

PMID- 22153539
TI  - Serum transforming growth factor-beta levels in patients with vitamin D
      deficiency.
AB  - BACKGROUND: Transforming growth factor-beta 1 (TGF-beta1) contributes to tissue
      repair by promoting tissue fibrosis, and elevations have been reported in
      patients with bone marrow fibrosis. The aim of this study was to evaluate the
      relationship between TGF-beta1 levels and vitamin D deficiency. METHODS: All
      patients presenting to the outpatient Endocrinology and Metabolic Diseases clinic
      between June and September of 2008 were approached, and consenting patients who
      were deemed suitable candidates were enrolled. Hematological parameters were
      measured, along with serum levels of total and ionized calcium, phosphorus,
      parathyroid hormone, iron, folic acid vitamin B12 levels, 25 OH vitamin D3
      (25OHD(3)) and TGF-beta1. RESULTS: A total of 132 patients were included in the
      study. Patients were divided into 4 groups based on levels of 25OHD(3) [group 1
      (<5 ng/ml), 20 patients; group 2 (5-15 ng/ml), 38 patients; group 3 (16-30
      ng/ml); and group 4 (>30 ng/ml), 28 patients]. TGF-beta1 levels were higher in
      patients in group 1 compared to the other groups. Transforming growth factor-beta
      levels correlated negatively with vitamin D3 and positively with leukocyte count,
      platelet count, of MCV and MCH. Multiple regression analyses revealed TGF-beta1
      levels to be associated with 25OHD(3) as well as with platelet count.
      CONCLUSIONS: Results of this study are suggestive of the presence of a
      significant relationship between TGF-beta and vitamin D deficiency. Increased TGF
      beta1 and platelet count may be an early indicator of bone marrow fibrosis in
      patients with vitamin D deficiency.

PMID- 22153540
TI  - The burden of diabetes mellitus in elderly patients from an Asian tertiary
      hospital.
AB  - SUMMARY: Diabetes mellitus (DM) has been declared as a global public health
      threat to society. However, the burden of the disease in elderly Asian patients
      has not been described. The aim of the study is to assess the disease burden of
      DM and its associated adverse outcomes in elderly patients from an Asian hospital
      using the hospital inpatient database. METHODS: Retrospective study of hospital
      discharge database from 2004 to 2008 to identify patients aged 65 years and above
      with DM and its associated 'adverse outcomes' using International Statistical
      Classification of Diseases and Related Health Problems, 9th Revision, Australian
      Modification (ICD-9-AM) codes. RESULTS: Of 89,875 hospitalized patients aged 65
      years and above over the 5 years, 31,124 (34.6%) patients had DM, and the
      percentage of DM cases increased steadily from 34.3% to 35.6%. Prevalence of DM
      associated adverse outcomes was higher in DM patients than in non-DM patients
      (53.8% vs. 31.5%, p<0.001). For trends over time, the adverse outcomes decreased
      in both DM patients (58.1% to 53.6%) and non-DM patients (34.3% to 31.4%, all
      p<0.001). All disease-specific adverse outcomes except renal disease decreased
      over time both in DM and non-DM patients (all p<0.05). There were increased
      trends over time for renal disease in both DM patients (16.1% to 23.2%, p<0.001)
      and non-DM patients (6.7% to 10.4%, p<0.001). CONCLUSION: The burden of DM in
      this group of elderly patients is high. Elderly patients with DM experienced much
      higher rates of the adverse outcomes.

PMID- 22153541
TI  - Home treatment of patients with acute cholecystitis.
AB  - BACKGROUND: Patients with acute cholecystitis are treated in Hospital. The aim of
      the study was to analyze the security and efficacy of treating not-operated-on
      patients with acute cholecystitis in Hospital in the Home (HIH). METHODS:
      Prospective study from January 2010 to May 2011 including all patients diagnosed
      with acute cholecystitis, not operated on and without comorbidities admitted to
      HIH Unit from the Emergency Department Short Stay Unit and Observation Unit.
      Patients were treated with ertapenem for at least one week. Intravenous treatment
      was followed by oral therapy to complete 14 days of antibiotic treatment. Patient
      characteristics, clinical course, need for return to hospital during admission to
      HIH, and admission to hospital in the month after discharge from HIH are
      analyzed. RESULTS: 25 patients were included. Mean age was 59 years (34-82). Upon
      arrival to the Emergency Department, all patients suffered abdominal pain, 60%
      had fever, and 32% vomiting. 48% of patients had a leukocyte count over 13,000
      cells/MUl. All patients had cholelithiasis and a distended gallbladder. 56%
      showed thickening of the gallbladder wall. Fluid accumulation around the
      gallbladder was noted in 16% of the cases. Murphy's sign proved positive in 44%.
      All patients showed a favorable course. No patient required hospital readmission
      during stay in HIH or in the month after discharge. All patients expressed their
      satisfaction with treatment at home. CONCLUSIONS: Patients with acute
      cholecystitis and without comorbidities can be safely and effectively treated in
      HIH after a short monitoring period in hospital.

PMID- 22153542
TI  - Hepato-systemic gradient of carbon monoxide in cirrhosis.
AB  - BACKGROUND AND AIMS: Experimental data suggest that in liver cirrhosis splanchnic
      and systemic vasculature exhibit marked endothelial Carbon monoxide (CO)
      overproduction, while recent data demonstrated heme oxygenase (HO) hyperactivity
      in the liver of rats with cirrhosis. No data are so far available on CO levels in
      the hepatic veins of cirrhotic patients. We aimed at evaluating whether plasma CO
      levels differ between systemic (peripheral vein) and hepatic (hepatic vein)
      circulation in patients with viral cirrhosis with and without ascites. METHODS:
      We enrolled 31 consecutive non-smoking in- or outpatients with liver cirrhosis.
      We measured wedge (occluded, WHVP) and free hepatic venous pressures (FHVP) and
      hepatic-vein pressure gradient (HVPG) was the calculated. Plasma level of NO and
      plasma CO concentration were determined both in peripheral vein and in the
      hepatic vein in cirrhotics. RESULTS: In cirrhotic patients plasma CO levels were
      significantly higher in the hepatic vein (16.66+/-10.71 p.p.m.) than in the
      peripheral vein (11.71+/-7.00 p.p.m). Plasma NO levels were significantly higher
      in peripheral vein (97.02+/-21.11 MUmol/ml) than in the hepatic vein (60.76+/
      22.93 MUmol/ml). CONCLUSIONS: In patients with liver cirrhosis we documented a
      hepato-systemic CO gradient as inferred by the higher CO values in the hepatic
      vein than in the peripheral vein. In cirrhotic patients, CO and NO exhibit
      opposite behavior in the liver, while both molecules show increased values in the
      systemic circulation. It can be speculated that increased intra-hepatic CO levels
      might represent a counterbalancing response to reduced NO intra-hepatic levels in
      human liver cirrhosis.

PMID- 22153543
TI  - Sperm DNA damage in patients with chronic viral C hepatitis.
AB  - INTRODUCTION: The aim of this study was to evaluate the conventional and
      biofunctional parameters of sperm in young infertile patients with Hepatitis C
      (HCV) infection. METHODS: Forty HCV patients with primary infertility, aged 27 to
      42 years (mean 36.4 years) and twenty HCV patients with secondary infertility
      aged 28 to 45 years (mean 35.0+/-2.8 years), underwent hormonal and sperm
      analysis in addition to the determination of reactive oxygen species (ROS)
      concentrations in the sperm and flow-cytometric evaluation. The following
      biofunctional sperm parameters were evaluated by flow cytometry: DNA
      fragmentation, mitochondrial membrane potential, chromatin condensation, and the
      rate of early apoptosis. RESULTS: Overall, patients with HCV showed significantly
      worse median values of conventional and biofunctional sperm parameters than
      control subjects, including sperm density (31.7 vs. 80.4 million/ml), forward
      motility (9.4 vs. 25%), normal forms (15.4 vs. 24.8%), DNA fragmentation (6.6 vs.
      2.2%), low MMP (45.5 vs. 8%), an early apoptosis rate (5 vs. 2.7%), and abnormal
      chromatin (18.9 vs. 13.9%). Finally, HCV patients had significantly higher basal
      (250 vs. 75*10(3)/cpm) and stimulated (550 vs. 120*10(3)/cpm) ROS levels in semen
      compared to control subjects. None of the examined parameters (sperm, hormonal,
      biofunctional and assessment of oxidative status in the semen) was significantly
      different between HCV patients with primary and secondary infertilities.
      DISCUSSION: These results confirm that HCV infection has a negative impact on
      sperm parameters. The overlap of the results observed in the two groups of HCV
      patients supports the hypothesis that HCV infection may cause to alterations in
      sperm parameters.

PMID- 22153544
TI  - Arthritis in patients with systemic sclerosis.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a connective tissue diseases
      characterised by excessive thickening of the dermis in addition to affection of
      internal organs. Many patients experience musculoskeletal symptoms, but arthritis
      is still considered to be a rare manifestation. Therefore, we analysed a cohort
      of SSc patients in our department and related the findings to published data.
      METHODS: Clinical data on inpatients with SSc between February 2007 and February
      2008 were analysed retrospectively for the presence of clinically overt and
      documented arthritis. In addition, X-rays of these patients were reassessed. A
      systematic literature search using PubMed was performed to find studies on
      arthritis in SSc patients; suitable studies were included in a meta-analysis
      based on the random-effect-model. The search terms were scleroderma, systemic
      sclerosis, arthritis, inflammatory joint disease, hand involvement, foot
      involvement and musculoskeletal findings in various combinations. Original
      articles not written in English and articles which were not dealing with
      arthritis in SSc patients were excluded from the study. We included articles in
      which the examined cohorts corresponds to the ACR- or LeRoy criteria for SSc and
      arthritis was diagnosed based on clinical and/or radiological data. All
      manuscripts were read and reviewed by two independent investigators. RESULTS: In
      our cohort of 58 patients, 31% had signs of arthritis, 19% clinically and 26%
      radiologically. In a meta-analysis of 7 studies, a prevalence of 26% (95% CI
      [16.7, 36.1]) for radiologically detectable arthritis in SSc patients was
      observed. For clinical arthritis, the prevalence was calculated to be 23% (95% CI
      [14.9, 30.9]). Of interest, no difference in the occurrence of arthritis in
      diffuse and limited SSc was observed radiologically (OR=1.1, 95% CI [0.47, 2.57])
      or clinically (OR=1.11, 95% CI [0.6, 2.05]). CONCLUSION: Arthritis is frequent
      manifestation of SSc. Its role in joint dysfunction has to be established in
      further studies.

PMID- 22153545
TI  - Analysis of the components of Chinese medical professionalism.

PMID- 22153546
TI  - Homocysteine, C677T MTHFR polymorphism and vascular risk in a Spanish population
      sample.

PMID- 22153547
TI  - Outcome of antiviral therapy in Egyptian Hepatitis C Virus (HCV) genotype 4
      patients with advanced liver fibrosis.

PMID- 22153548
TI  - Polypathological patients and prognostic scores.

PMID- 22153549
TI  - Relationship of C-reactive protein with components of the metabolic syndrome in a
      Tunisian population.
AB  - BACKGROUND: C-reactive protein (CRP) is an independent risk factor of diabetes
      and cardiovascular disease and it is proposed as a component of metabolic
      syndrome (MS). This study was undertaken to investigate the relationship between
      CRP and various characteristics of the MS in a sample of the Tunisian population
      METHODS: One hundred and forty nine patients with MS and 152 controls, aged 35-70
      years were recruited. Waist circumference (WC), blood pressure, HDL-cholesterol
      (HDL-C), triglycerides (TG), glucose, insulin and CRP were measured. Insulin
      resistance was assessed by homeostasis model assessment of insulin resistance
      (HOMA-IR). MS was defined by NCEP-ATPIII report RESULTS: CRP levels were
      significantly higher in MS group (4.41+/-3.73 mg/L vs. 2.68+/-2.59 mg/L, p<0.001)
      compared to without MS group. For both sexes, CRP increased as the number of MS
      components increased (p=0.015 for men and p<0.001) after adjustment for age,
      smoking, alcohol intake and, for women, menopause. There were statistically
      significant positive correlations for log CRP with WC, log TG, and log HOMA-IR in
      both sexes adjusted for confounding factors listed above. A significant negative
      correlation was found between HDL-C and log CRP only in women. In both sexes, WC
      was identified, by multiple linear regression models, as significant independent
      predictor of CRP level variability. HDL-C showed also a significant contribution
      only in women CONCLUSIONS: The present study provides evidence that CRP levels
      are elevated in MS subjects. In addition, WC and HDL-C are significant predictors
      of the CRP elevation.

PMID- 22153550
TI  - Neurocognitive function in destination therapy patients receiving continuous-flow
      vs pulsatile-flow left ventricular assist device support.
AB  - BACKGROUND: The HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow left
      ventricular assist device (LVAD) improved survival in destination therapy (DT)
      patients during a randomized trial compared with pulsatile-flow LVADs. This study
      documented changes in cognitive performance in DT patients from that trial to
      determine if there were differences between continuous-flow and pulsatile-flow
      support. METHODS: Data were collected in a sub-study from 96 HeartMate II
      continuous-flow and 30 HeartMate XVE pulsatile-flow LVAD patients from 12 of the
      35 trial sites that followed the same serial neurocognitive (NC) testing protocol
      at 1, 3, 6, 12, and 24 months after LVAD implantation. Spatial perception,
      memory, language, executive functions, and processing speed were the domains
      assessed with 10 standard cognitive measures. Differences over time and between
      LVAD type were evaluated with linear mixed-effects modeling. RESULTS: From 1 to
      24 months after LVAD implantation, changes in NC functions were stable or showed
      improvement in all domains, and there were no differences between the continuous
      flow and pulsatile-flow groups. Data at 24 months were only available from
      patients with the continuous-flow LVAD due to the limited durability of the
      HeartMate XVE device. There was no decline in any NC domain over the time of LVAD
      support. Missing data not collected from patients who died could have resulted in
      a bias toward inflated study results. CONCLUSIONS: The NC performance of advanced
      heart failure patients supported with continuous-flow and pulsatile-flow LVADs
      shows stabilization or improvement during support for up to 24 months.

PMID- 22153551
TI  - A longitudinal study of the course of asymptomatic antibody-mediated rejection in
      heart transplantation.
AB  - BACKGROUND: Growing evidence suggests worse cardiac allograft vasculopathy and
      mortality in patients with asymptomatic antibody-mediated rejection (AMR). Debate
      continues about whether therapeutic intervention is warranted to avoid adverse
      outcomes. In this study we examine the course of individual episodes of untreated
      asymptomatic AMR on follow-up endomyocardial biopsy (EMB). METHODS: The U.T.A.H.
      Cardiac Transplant Program database was queried for transplant recipients between
      1985 and 2009 who survived beyond 1 year and had at least 1 episode of lone AMR
      with a follow-up EMB. All EMBs were screened for AMR by immunofluorescence and
      graded for severity. Data were analyzed based on time from transplant (early,
      <=12 months; late, >12 months). RESULTS: Nine hundred fifty-eight patients with a
      total of 15,448 biopsies qualified for the study. Average age at transplant was
      46.7 years; 13% of the patients were female. Within the first year post
      transplant, asymptomatic AMR was diagnosed in 13.6% of biopsies compared with
      5.2% beyond 1 year. AMR resolved in 65% (early) vs 75% (late) on follow-up EMB.
      More severe AMR was less likely to improve regardless of time from transplant.
      Furthermore, after an episode of AMR had resolved, the recurrence rate at 3, 6
      and 12 months was 44%, 50.1% and 56.2%, respectively. CONCLUSIONS: The incidence
      of AMR is higher in the first year post-transplant and the likelihood of
      resolution is less on follow-up EMB, especially when more severe. A small but
      significant number of cases became worse or did not change. These new findings
      may be helpful in planning future studies that test whether therapeutic
      interventions on asymptomatic AMR favorably impact outcomes.

PMID- 22153552
TI  - Lung preservation in experimental ischemia/reperfusion injury and lung
      transplantation: a comparison of natural and synthetic surfactants.
AB  - BACKGROUND: Surfactant inactivation results from ischemia/reperfusion injury and
      plays a major role in the pathogenesis of primary graft dysfunction after
      clinical lung transplantation. Thus, prophylactic administration of exogenous
      surfactant preparations before the onset of ischemia/reperfusion has proven to be
      effective in preserving pulmonary structure and function. Various natural and
      synthetic surfactant preparations exhibit differences regarding the biochemical
      composition and biophysical properties. METHODS: In this study we compared the
      efficacy of preservation of pulmonary structure and function of the natural
      surfactant preparations Curosurf and Survanta to that of a synthetic surfactant
      containing an analog of surfactant protein C (SPC-33) in a rat model of
      ischemia/reperfusion injury. The oxygenation capacity and peak inspiratory
      pressure during the reperfusion period were recorded. By applying design-based
      stereology at the light- and electron-microscopic level, pathologic alterations,
      including alveolar edema, injury of the blood-air barrier and the intra-alveolar
      as well as intracellular surfactant pools, were quantified. RESULTS: The best
      oxygenation and preservation of lung structure was achieved with Curosurf.
      Survanta treatment was associated with the most severe injury of the blood-air
      barrier, and SPC-33 demonstrated signs of microatelectasis. The intra-alveolar
      surfactant pool after Curosurf and SPC-33 was dominated by active surfactant
      subtypes, whereas Survanta was associated with the highest fraction of inactive
      surfactant. The intracellular surfactant pool did not show any differences
      between the treatment groups. CONCLUSIONS: Taken together, Curosurf achieved the
      best structural and functional lung preservation, whereas Survanta was inferior
      to both Curosurf and SPC-33.

PMID- 22153553
TI  - Ultrastructural changes in acute lung allograft rejection: novel insights from an
      animal study.
AB  - BACKGROUND: Acute rejection (AR) episodes after lung transplantation (Tx) are
      orchestrated by cells of the innate and adaptive immune system targeting the
      engrafted organ. The assessment and classification of pathologic changes of AR
      relies essentially on conventional histology. Herein we apply the technique of
      scanning electron microscopy (SEM) to identify and characterize ultrastructural
      changes of the pulmonary graft after lung Tx. METHODS: Orthotopic single-lung Tx
      was performed between BALB/c (donor) and C57BL/6 (recipient) mice. At Day 5 after
      Tx, lung allografts were recovered for SEM and for histologic analysis. RESULTS:
      Upon Tx, high numbers of leukocytes and thrombocytes were found, showing an
      activated surface pattern and a change of their cell body shape. These cells
      adhered and partly transmigrated through the endothelium of vessels. Larger
      vessels were more affected than smaller vessels and the endothelium was roughened
      in its surface texture throughout. As a phenomenon, airways were partly covered
      by activated dendritic cells. Numerous thrombocytes and macrophages accumulated
      on the endothelium of the cuff anastomosis region exposing this area to a
      particularly higher risk of thrombosis. CONCLUSIONS: SEM allows for detection of
      morphologic changes during pulmonary allograft rejection and adds important data
      to conventional histology when making the diagnosis of acute rejection.

PMID- 22153554
TI  - A high-intensity exercise program improves exercise capacity, self-perceived
      health, anxiety and depression in heart transplant recipients: a randomized,
      controlled trial.

PMID- 22153555
TI  - Increased lipofuscin on endomyocardial biopsy predicts greater cardiac
      improvement in adolescents and young adults.
AB  - BACKGROUND: The presence of interstitial fibrosis and lipofuscin in
      endomyocardial biopsies may indicate the chronicity of heart failure. Fibrosis is
      known to increase in the failing heart. Lipofuscin increases with age, but its
      relationship to heart function is unknown. This study investigated whether
      lipofuscin or fibrosis had predictive utility in indicating function or adverse
      event (death, transplant, assist device placement) at 1 year postbiopsy in
      adolescents and young adults. METHODS: A retrospective analysis was performed on
      nontransplant endomyocardial biopsies between 2000 and 2009 from individuals aged
      10-40 years. Clinical and demographic information including ejection fraction
      (EF), EF at 1 year, and adverse events were obtained as available. Lipofuscin and
      fibrosis were scored retrospectively in a blinded fashion for 201 biopsies.
      Linear regression and Cox proportional hazard models were used for multivariable
      analysis. RESULTS: Increasing lipofuscin strongly correlated with patient age
      (P<.0001). Higher lipofuscin levels were correlated with a better EF at 1 year
      (P=.02). This remained significant (P=.04) after adjusting for age. The degree of
      fibrosis did not associate with any clinical variable and had no predictive
      capabilities in this study. CONCLUSIONS: This is the first study to incorporate
      lipofuscin in predicting future heart function. We found that more lipofuscin
      correlates with better EFs at 1 year, suggesting that lipofuscin is a marker for
      improved cardiac compensation. This information can help clinicians devise
      treatment plans for individuals in this age group.

PMID- 22153556
TI  - The first cardiac transplant experience in a patient with mucopolysaccharidosis.
AB  - Hunter syndrome (MPSII) is a rare X-linked lysosomal storage disorder that can
      affect multiple systems but primarily affects the heart. We report the case of a
      previously asymptomatic 23-year-old patient who had an attenuated form of MPSII
      and presented with refractory heart failure that required a heart transplant. The
      diagnosis was confirmed by detection of an increase in urinary excretion of
      glycosaminoglycans, a deficiency in enzymatic activity, and molecular analysis. A
      myocardial biopsy revealed hypertrophic cardiomyocytes, mild fibrosis, and
      lysosomal storage in interstitial cells. Molecular analysis identified a novel
      mutation in the iduronate-2-sulfatase gene. Although the clinical outcome was not
      favorable, we believe that this approach may be valid in end-stage heart failure.

PMID- 22153557
TI  - Survival of TNF-alpha antagonists in rheumatoid arthritis: a long-term study.
AB  - OBJECTIVES: To investigate the efficacy, safety and survival of tumour necrosis
      factor (TNF) alpha antagonists in patients with rheumatoid arthritis (RA).
      METHODS: One hundred and fifty-one RA patients treated with TNF-alpha inhibitors
      during the time period 2000 to 2009 were studied. Kaplan-Meier statistic analysis
      was applied, in which discontinuation from anti-TNF-alpha therapy was used as the
      terminal event. RESULTS: Eighty-two patients received infliximab, 49 adalimumab
      and 20 etanercept: they were followed up over 7, 5 and 4 years, respectively.
      Anti-TNF-alpha therapy resulted in a rapid clinical improvement associated with a
      reduction in inflammatory markers in the first year of the treatment, which was
      sustained throughout the following years. Ninety (59.6%) patients were withdrawn
      during the observational period overall. The patients who discontinued
      infliximab, adalimumab and etanercept therapy were 55/82 (67.1%), 27/49 (55.1%)
      and 8/20 (40%) respectively. The main reasons for discontinuation were drug
      adverse events and inefficacy. According to Kaplan-Meier methods, the 'survival
      rate' of infliximab after the first year of treatment reached 82.9%, while after
      7 years the proportion was 32.9%. With regard to adalimumab, after the first year
      of treatment its 'survival rate' was 83.7% and after 5 years it reached 44.9%. As
      far as etanercept is concerned, after the first year of treatment, the 'survival
      rate' reached 70% and after 4 years it remained 60%. CONCLUSIONS: TNF-alpha
      antagonists constitute an effective therapeutic option for patients with RA
      refractory to disease-modifying anti-rheumatic drugs. They demonstrate an
      acceptable safety profile. Their survival rate is high in the first years of
      treatment, while after the fifth year it decreases considerably.

PMID- 22153558
TI  - A long duration of the prediagnostic symptomatic interval is not associated with
      an unfavourable prognosis in childhood medulloblastoma.
AB  - BACKGROUND: Due to the lacking specificity of symptoms making a correct diagnosis
      can be a challenge in children with medulloblastoma. This can lead to
      prediagnostic symptomatic intervals (PSIs) of several weeks to months. It is
      unknown whether the length of the PSI is associated with an inferior survival
      outcome in this population. METHODS: To study the association of PSI with disease
      stage at diagnosis, tumour control and survival in children with medulloblastoma,
      prospectively collected data on PSI, clinical, and biological features were
      analysed in 224 patients diagnosed at the age of 3-18 years and treated within
      the prospective randomised multicentre trial HIT'91. RESULTS: Patients with lower
      stage disease tended towards a longer median PSI than those with higher-stage
      disease (M0 stage, 2.0 months; M1 stage, 2.0 months; M2/M3 stage, 1 month; p =
      0.094. M0/1 stage versus M2/3 stage; p = 0.025). The patient group with the
      longest PSI had the best survival outcome (PSI >= 4.0 months: 10-year overall
      survival rate (OS), 71%; PSI < 4.0 months, 10-year OS, 61%; p = 0.056). Age at
      diagnosis was positively correlated with PSI (p = 0.027). No associations were
      found between PSI and sex histological subtype, presence of postoperative
      residual tumour, or c-myc and TrkC mRNA expression. CONCLUSION: Contrary to a
      common belief that a longer PSI may adversely affect prognosis, a longer PSI was
      associated with a trend towards lower metastatic stage and better survival
      probabilities. Nevertheless these findings do not obviate the importance of a
      timely diagnosis in paediatric patients with medulloblastoma.

PMID- 22153559
TI  - [End of a phase].

PMID- 22153560
TI  - [Summary of the information sheet for users. Wound care].

PMID- 22153561
TI  - [Summary of the information sheet for users. Bladder catheterization and
      prevention of urinary tract infections].

PMID- 22153563
TI  - The precautionary principle in blood safety: not quite the same as aiming for
      zero risk.

PMID- 22153564
TI  - [Adrenal endothelial cyst with a preoperative image suggesting malignancy].

PMID- 22153565
TI  - [Patient with diabetes and impaired hearing].

PMID- 22153566
TI  - Pre-exposure prophylaxis for HIV prevention: how to predict success.

PMID- 22153567
TI  - An observational non-interventional study of people with diabetes beginning or
      changed to insulin analogue therapy in non-Western countries: the A1chieve study.
AB  - AIM: The aim of A(1)chieve was to remedy the deficit of data on the efficacy and
      safety of insulin analogues in routine clinical care in less well-resourced/newly
      developed countries. METHODS: A non-interventional, 6-month, observational study
      of 66,726 people with type 2 diabetes, both insulin users and non-insulin users,
      started on insulin detemir, insulin aspart or biphasic insulin aspart in 28
      countries across four continents. RESULTS: Baseline HbA(1c) (+/-SD) was poor: 9.5
      +/- 1.8%. At 6 months, improvement was -2.1 +/- 1.7% in the entire cohort, and 
      2.2 +/- 1.7% and -1.8 +/- 1.7% for prior non-insulin users and insulin users. All
      three analogue therapies gave similar results, again independently of prior
      insulin use, but also from seven pre-specified country groupings. Overall,
      hypoglycaemia did not increase in those new to insulin, and fell in those
      switching insulins. There was no change in body weight (-0.1 +/- 3.7 kg), while
      lipid profile and systolic blood pressure (-6.3 +/- 17.1 mmHg) were improved.
      CONCLUSIONS: Beginning insulin analogue therapy in people with type 2 diabetes
      and poor blood glucose control is associated with marked improvements in diverse
      aspects of vascular risk factor profile without evidence of clinically
      significant safety or tolerability problems.

PMID- 22153568
TI  - Improvements in quality of life associated with insulin analogue therapies in
      people with type 2 diabetes: results from the A1chieve observational study.
AB  - AIMS: To determine the effects on quality of life after starting insulin with, or
      switching to, insulin analogue therapies in the 24-week, prospective, non
      interventional, observational A(1)chieve study conducted across four continents
      in people with type 2 diabetes. METHODS: Health-related quality of life (HRQoL)
      was assessed at baseline and at 24 weeks by the validated EQ-5D questionnaire
      (visual analogue score [VAS] and five dimensions) in 66,726 people who had
      started using basal insulin detemir, mealtime insulin aspart (with or without a
      basal insulin) or biphasic insulin aspart 30. RESULTS: For the overall cohort,
      reported HRQoL increased significantly by 13.8 points from 63.4 points at
      baseline to 77.2 points at 24 weeks (p<0.001) (scale 1-100, 100=best health
      imaginable). Beginning or changing insulin was associated with a significant
      increase in HRQoL score (+15.0 points and +11.1 points, respectively), resulting
      in a similar score at 24 weeks in the two populations (77.8 and 75.9 points).
      Reported HRQoL also increased statistically significantly in people administering
      any insulin analogue regimen and across all regions, although there were some
      marked regional differences in reported HRQoL at baseline. CONCLUSION: Compared
      with baseline scores, beginning insulin with, or switching to, insulin analogue
      therapies are associated with increased HRQoL.

PMID- 22153569
TI  - World Diabetes Congress 2011: turning policy into action after the UN High-Level
      Summit on NCDS.

PMID- 22153570
TI  - Comparison and validation of capacitive accelerometers for health care
      applications.
AB  - Fall detection, gait analysis and context recognition are examples of
      applications where capacitive accelerometers are widely used in health care. In
      most of the existing work, algorithms were developed for a specific platform and
      accelerometers were used without explicitly choosing a specific type. With this
      work we present an inexpensive and practical test setup for replicable and
      repeatable testing of accelerometers. In addition we use this setup to evaluate
      six of the most commonly available accelerometers today and list their outcomes
      for linearity, power consumption and correlation of the tested sensors. We also
      attempt to an answer to the question of whether applications and algorithms
      developed for one platform and one type of accelerometer can be easily
      transferred to another accelerometer.

PMID- 22153571
TI  - A hominid tooth from Bulgaria: the last pre-human hominid of continental Europe.
AB  - A hominid upper premolar was discovered in the Azmaka quarry, near Chirpan
      (Bulgaria). The associated fauna, especially the co-occurrence of Choerolophodon
      and Anancus among the proboscideans, and Cremohipparion matthewi and Hippotherium
      brachypus among the hipparions, constrains the age of the locality to the second
      half of the middle Turolian (ca. 7 Ma), making it the latest pre-human hominid of
      continental Europe and Asia Minor. The available morphological and metric data
      are more similar to those of Ouranopithecus from the Vallesian of Greece than to
      those of the early to middle Turolian hominids of Turkey and Georgia, but the
      time gap speaks against a direct phyletic link, and Turolian migration from the
      east cannot be rejected.

PMID- 22153572
TI  - Impact of body mass index on compliance and persistence to adjuvant breast cancer
      therapy.
AB  - Several authors found that the prognosis of overweight and obese breast cancer
      (BC) patients was lower than that of normal weight patients. We present the first
      study which evaluates the impact of body mass index (BMI) on compliance (i.e. to
      start a recommended therapy) and persistence to adjuvant BC therapy. An
      unselected cohort of 766 patients (<=75 years) diagnosed from 1997 to 2009 was
      analyzed in relevance to the four adjuvant therapy modalities: (A) radiation, (B)
      chemotherapy, (C) therapy with trastuzumab, and (D) endocrine therapy. With
      respect to compliance, multivariate analyses calculated Odds ratios (ORs) >1 for
      increased BMI in all four therapy modalities, i.e. increased BMI had a positive
      influence on compliance. The results were significant for radiotherapy
      (OR,2.37;95%CI,1.45-3.88;p < 0.001) and endocrine therapy (OR,1.92;95%CI,1.21
      3.04;p = 0.002) and showed a trend in chemotherapy (OR,1.42;95%CI,0.97-2.08;p =
      0.063). Analyzing persistence, increasing BMI had ORs <1 for chemotherapy and
      therapy with trastuzumab, both not reaching statistical significance. For
      endocrine therapy, increasing BMI was a significant predictor for persistence
      (OR,1.35;95%CI,1.08-1.80;p = 0.042). Failure of compliance and persistence to
      adjuvant therapy does not pose a contributing factor for the observed unfavorable
      prognosis in overweight/obese BC patients. In most therapy modes, patients with
      increasing BMI demonstrated a higher motivation and perseverance to the
      recommended treatment.

PMID- 22153573
TI  - SPECT/CT scans allow precise anatomical location of sentinel lymph nodes in
      breast cancer and redefine lymphatic drainage from the breast to the axilla.
AB  - BACKGROUND: Historical studies of lymphatic drainage of the breast have suggested
      that the lymphatic drainage of the breast was to lymph nodes lying in the antero
      pectoral group of nodes in the axilla just lateral to the pectoral muscles. The
      purpose of this study was to confirm this is not correct. METHODS: The hybrid
      imaging method of SPECT/CT allows the exact anatomical position of the sentinel
      lymph node (SLN) in the axilla to be documented during pre-operative
      lymphoscintigraphy (LS) in patients with breast cancer. We have done this in a
      series of 741 patients. The Level I axillary nodes were defined as anterior, mid
      or posterior. This was related to the anatomical location of the primary cancer
      in the breast. RESULTS: A SLN was found in the axilla in 97.8% of our patients.
      Just under 50% of SLNs located in the axilla were not in the anterior group and
      lay in the mid or posterior group of Level I axillary nodes. There was a SLN in a
      single node field in 460 patients (63%), two node fields in 261(36%), three node
      fields in 6 and four node fields in 1 patient. CONCLUSION: Axillary lymphatic
      drainage from the breast is not exclusively to the anterior (or antero-pectoral)
      group of Level I nodes. SYNOPSIS: SPECT/CT lymphoscintigraphy shows that the
      breast does not always drain to the anterior group of Level I lymph nodes in the
      axilla but may drain to the mid axilla and/or posterior group in about 50% of
      patients with breast cancer regardless of the location of the cancer in the
      breast. These data redefine lymph drainage from the breast to axillary lymph
      nodes.

PMID- 22153574
TI  - [French guidelines on the use of repetitive transcranial magnetic stimulation
      (rTMS): safety and therapeutic indications].
AB  - During the past decade, a large amount of work on transcranial magnetic
      stimulation (TMS) has been performed, including the development of new paradigms
      of stimulation, the integration of imaging data, and the coupling of TMS
      techniques with electroencephalography or neuroimaging. These accumulating data
      being difficult to synthesize, several French scientific societies commissioned a
      group of experts to conduct a comprehensive review of the literature on TMS. This
      text contains all the consensual findings of the expert group on the mechanisms
      of action, safety rules and indications of TMS, including repetitive TMS (rTMS).
      TMS sessions have been conducted in thousands of healthy subjects or patients
      with various neurological or psychiatric diseases, allowing a better assessment
      of risks associated with this technique. The number of reported side effects is
      extremely low, the most serious complication being the occurrence of seizures. In
      most reported seizures, the stimulation parameters did not follow the previously
      published recommendations (Wassermann, 1998) [430] and rTMS was associated to
      medication that could lower the seizure threshold. Recommendations on the safe
      use of TMS / rTMS were recently updated (Rossi et al., 2009) [348], establishing
      new limits for stimulation parameters and fixing the contraindications. The
      recommendations we propose regarding safety are largely based on this previous
      report with some modifications. By contrast, the issue of therapeutic indications
      of rTMS has never been addressed before, the present work being the first attempt
      of a synthesis and expert consensus on this topic. The use of TMS/rTMS is
      discussed in the context of chronic pain, movement disorders, stroke, epilepsy,
      tinnitus and psychiatric disorders. There is already a sufficient level of
      evidence of published data to retain a therapeutic indication of rTMS in clinical
      practice (grade A) in chronic neuropathic pain, major depressive episodes, and
      auditory hallucinations. The number of therapeutic indications of rTMS is
      expected to increase in coming years, in parallel with the optimisation of
      stimulation parameters.

PMID- 22153575
TI  - Are proinflammatory cytokines involved in an increased risk for depression by
      unhealthy diets?
AB  - Depression is a highly prevalent mental illness, which is associated with
      substantial functional impairment. Many factors, like especially genetic risk and
      stressful life events, are being discussed to be involved in the pathogenesis of
      the disease. There is also evidence that elevated levels of proinflammatory
      cytokines, which are frequently found in depressed individuals, could contribute
      to the development of the disease. Patients with metabolic syndrome also show a
      chronic low grade of inflammation. In addition, epidemiological studies suggest
      that an unhealthy dietary eating pattern, consisting of high amounts of refined
      grains and softdrinks, red and processed meat, fatty dairy products, and little
      amounts of vegetables, fruits and fish is associated with higher levels of major
      inflammatory cytokines, like Interleukin-6, and the acute phase C-reactive
      protein, even after controlling for body mass index. Furthermore, several recent
      studies suggest that an unhealthy diet quality is associated with an increased
      risk of depression. Therefore the connection between regular consumption of
      unhealthy foods, chronic inflammation, and increased risk for depression seems
      plausible.

PMID- 22153576
TI  - Renal cell carcinoma: resistance to therapy, role of apoptosis, and the
      prognostic and therapeutic target potential of TRAF proteins.
AB  - Renal cell carcinoma (RCC) is the commonest of the renal neoplasms. Although
      surgery and cryoablation are successful curative treatments for localized RCC,
      most patients are diagnosed with advanced or metastatic RCC, which has a poor
      prognosis. RCC are a heterogeneous set of cancers that have traditionally been
      classified and staged using cellular characteristics, size, local extension and
      distant metastases. Current staging systems provide good prognostic information,
      but it is very likely that the identification of new more accurate and predictive
      prognostic markers, not currently included in traditional staging systems, will
      improve the outcome for RCC patients. For this reason, increased knowledge of the
      underlying molecular characteristics of RCC development and progression is
      necessary. In most cancers, but especially RCC, deregulated control of apoptosis
      contributes to cancer growth by aberrantly extending cell viability and
      facilitating resistance to cancer therapies. Here we present the hypothesis that
      select members of the tumor necrosis factor (TNF) superfamily, the TNF receptor
      associated factors (TRAFs), have a role in RCC apoptosis and may have prognostic
      significance for RCC. Candidate biomarkers for RCC are few, and the TRAFs may be
      important inclusions in panels of biomarkers for RCC. TRAFs may also be potential
      molecular targets for new therapies, either through their ability to promote
      apoptosis in the cancers themselves, or through their ability to modulate the
      immune defence against cancer progression. Some support data are presented here
      for our hypothesis. However, these novel concepts need further careful analysis
      to allow clinicians and oncologists any assistance for earlier detection of RCC
      and for characterizing patients with RCC for individualised targeted therapy.

PMID- 22153577
TI  - A new three-dimensional model for emotions and monoamine neurotransmitters.
AB  - The monoamines serotonin, dopamine and noradrenaline have a great impact on mood,
      emotion and behavior. This article presents a new three-dimensional model for
      monoamine neurotransmitters and emotions. In the model, the monoamine systems are
      represented as orthogonal axes and the eight basic emotions, labeled according to
      Tomkins, are placed at each of the eight possible extreme values, represented as
      corners of a cube. The model may help in understanding human emotions,
      psychiatric illness and the effects of psychotropic drugs. However, further
      empirical studies are needed to establish its validity.

PMID- 22153578
TI  - Reduction in the incidence of ventilator-associated pneumonia: a
      multidisciplinary approach.
AB  - BACKGROUND: We report the process implemented in our institution by a task force
      focused on the reduction of ventilator-associated pneumonia (VAP). METHODS:
      Retrospective cohort study of all adults admitted to one of our 4 adult ICUs,
      intubated on invasive mechanical ventilation. We  implemented a ventilator bundle
      in April of 2007; we report the incidence of VAP in 2008, and, after adjustment
      in the process (oral care performed by respiratory therapists), the incidence in
      2009. The primary outcome was reduction of the microbiologically confirmed VAP
      rate over a 2 year  period. Other outcomes were duration of mechanical
      ventilation, antibiotic days, ICU and hospital stay, and mortality. RESULTS:
      During the study period, 2,588 patients received invasive mechanical ventilation
      in the adult ICUs. The VAP rate during 2008 was 4.3/1,000 ventilator days, and
      the  2009 rate was 1.2/1,000 ventilator days. The 2008 to 2009 VAP rate ratio was
      significantly greater than 1 (rate ratio 3.6, 95% CI 1.8-8.0, P < .001).
      Antibiotic days were less in 2009 versus 2008 (Hodges-Lehmann estimate of
      difference between 2008 and 2009, 1.0, 95% CI 0.0-1.0,  P = .002). The median
      stay in the ICU was unchanged, and in the hospital was decreased in 2009 (Hodges
      Lehmann estimate of difference between 2008 and 2009, 1.0, 95% CI 0.0-1.0, P <
      .001). The hospital mortality was 26.1%, and there was no difference between the
      2 years.  Adherence with the ventilator bundle was above 92% during the study
      period, but the oral care adherence improved from 33% to 97% after respiratory
      therapists assumed oral care. CONCLUSIONS: Reduction of the incidence of VAP
      occurred with an intervention that included respiratory therapists  doing oral
      care in patients receiving invasive mechanical ventilation. Oral care done by
      respiratory therapists may be associated with reduction of VAP.

PMID- 22153579
TI  - Looking forward for Cardiovascular Pathology.

PMID- 22153580
TI  - Empyema caused by Legionella pneumophila.

PMID- 22153581
TI  - Prognostic influence of loss of blood group A antigen expression in pathologic
      stage I non-small-cell lung cancer.
AB  - INTRODUCTION: In the scientific literature, contradictory results has been
      published on the prognostic value of the loss of expression of blood group
      antigen A (BAA) in lung cancer. The objective of our study was to analyze this
      fact in our surgical series. PATIENTS AND METHODS: In a multicenter study, 402
      non-small-cell lung cancer (NSCLC) patients were included. All were classified as
      stage-I according to the last 2009-TNM classification. We analyzed the prognostic
      influence of the loss of expression of BAA in the 209 patients expressing blood
      group A or AB. RESULTS: The 5-year cumulative survival was 73% for patients
      expressing BAA vs 53% for patients with loss of expression (P=.03). When patients
      were grouped into stages IA and IB, statistical significance was only observed in
      stage I-A (P=.038). When we analyzed the survival according to histologic type,
      those patients with adenocarcinoma and loss of expression of BAA had a lower
      survival rate that was statistically very significant (P=.003). The multivariate
      analysis showed that age, gender and expression of BAA were independent
      prognostic factors. CONCLUSIONS: The loss of expression of blood group antigen A
      has a negative prognostic impact in stage I NSCLC, especially in patients with
      adenocarcinoma.

PMID- 22153582
TI  - Stigma as a barrier to recovery from mental illness.
AB  - Advances in neuroscience, technology and research sophistication have greatly
      increased understanding of mental illnesses and improved the treatment of these
      disorders. However, there are also important psychosocial aspects of mental
      illness that play a significant role in recovery from these conditions. One set
      of these factors involves the prejudice and discrimination, often referred to as
      'stigma', faced by people when others learn that they have been diagnosed with,
      and/or treated for, a mental disorder.

PMID- 22153583
TI  - What is neuropsychoanalysis? Clinically relevant studies of the minded brain.

PMID- 22153584
TI  - [Kounis syndrome type I].

PMID- 22153585
TI  - [Cardiovascular disease based on gender: myths and evidence].

PMID- 22153586
TI  - Successful outcome of two pregnancies in patients with adult-onset Still's
      disease treated with IL-1 receptor antagonist (anakinra).
AB  - Adult onset Still's disease (AOSD) is an uncommon, systemic, inflammatory
      disorder of unknown etiology, characterised by spiking fevers, skin rash, and
      arthritis. Treatment consists of glucocorticosteroids and immunosuppressive
      drugs. Over the last few years it has become increasingly evident that treatment
      with the IL-1 receptor antagonist (IL-1RA) anakinra is highly effective even in
      patients with intractable disease. So far, there are scant data available on the
      effects of anakinra in pregnancy. We report two patients with AOSD who
      successfully gave birth while treated with anakinra during pregnancy.

PMID- 22153587
TI  - Poisoned social climate, collective responsibility, and the abuse at Abu Ghraib-
      Or, the establishment of "rule that is lack of rule".
AB  - The authors draw upon the experiences of one of the co-authors as an expert
      witness in sociology for mitigation at three of the courts-martial pertaining to
      the abuse at Abu Ghraib that were held at Ft. Hood, Texas in the year 2005 (for
      Javal Davis, Sabrina Harman, and Lynndie England). In addition, this paper is
      based upon the thousands of pages of affidavits, testimony, and U.S. Government
      reports concerning Abu Ghraib. These internal government reports, as well as the
      Levin-McCain report, point to collective responsibility and the responsibility of
      individuals high in the chain of command for establishing unlawful techniques. We
      review the shortcomings of a purely psychological approach for understanding the
      abuse, and turn to Durkheim's original understanding of anomie as a state of
      social derangement or rule by lack of rule to introduce the ideas of the social
      origins of and social responsibility for the abuse. We conclude with sociological
      suggestions for reforming some of the legal, medical, psychiatric, and other
      professional complicity in the abuse at Abu Ghraib.

PMID- 22153588
TI  - French lay people's views regarding the acceptability of involuntary
      hospitalization of patients suffering from psychiatric illness.
AB  - PURPOSE: To understand how lay people and health professionals in France judge
      the acceptability of hospitalizing a psychiatric patient against his will.
      METHODS: 123 lay people, 20 nurses, 5 psychologists, and 6 physicians judged the
      acceptability of involuntary hospitalization in each of 36 scenarios consisting
      of all combination of 4 factors: patient's adherence to treatment (agrees to take
      his medications or not); risk of suicide (none, immediate, multiple past
      attempts); risk of harming others (none, immediate, history of violence against
      others); attitude of patient's family (favorable to involuntary hospitalization
      or not). The judgment data were subjected to cluster analysis and subsequently to
      analysis of variance. RESULTS: 4 clusters were identified and labeled according
      to the factors that affected judgments: Never Favorable (7 participants, with
      mean acceptability judgment of 1.30 on a scale of 0-10); Threat to Others (35,
      with mean judgment of 8.68 when risk high, 2.94 when risk low), Threat to Others
      or Self and Adherence (88, with mean judgment of 6.89), and Always Favorable (24,
      with mean judgment of 8.41). CONCLUSIONS: 95% of participants agreed that
      involuntary hospitalization is acceptable under certain conditions, especially -
      in accordance with French law - when the patient presents a risk to others.

PMID- 22153589
TI  - Abnormal functional connectivity in children with attention-deficit/hyperactivity
      disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is typically
      characterized by symptoms of inattention and hyperactivity/impulsivity, but there
      is increased recognition of a motivation deficit too. This neuropathology may
      reflect dysfunction of both attention and reward-motivation networks. METHODS: To
      test this hypothesis, we compared the functional connectivity density between 247
      ADHD and 304 typically developing control children from a public magnetic
      resonance imaging database. We quantified short- and long-range functional
      connectivity density in the brain using an ultrafast data-driven approach.
      RESULTS: Children with ADHD had lower connectivity (short- and long-range) in
      regions of the dorsal attention (superior parietal cortex) and default-mode
      (precuneus) networks and in cerebellum and higher connectivity (short-range) in
      reward-motivation regions (ventral striatum and orbitofrontal cortex) than
      control subjects. In ADHD children, the orbitofrontal cortex (region involved in
      salience attribution) had higher connectivity with reward-motivation regions
      (striatum and anterior cingulate) and lower connectivity with superior parietal
      cortex (region involved in attention processing). CONCLUSIONS: The enhanced
      connectivity within reward-motivation regions and their decreased connectivity
      with regions from the default-mode and dorsal attention networks suggest impaired
      interactions between control and reward pathways in ADHD that might underlie
      attention and motivation deficits in ADHD.

PMID- 22153590
TI  - Nociceptin/orphanin FQ blockade of corticotropin-releasing factor-induced gamma
      aminobutyric acid release in central amygdala is enhanced after chronic ethanol
      exposure.
AB  - BACKGROUND: The central nucleus of the amygdala (CeA) mediates stress- and
      addiction-related processes. Corticotropin-releasing factor (CRF) and
      nociceptin/orphanin FQ (nociceptin) regulate ethanol intake and anxiety-like
      behavior. In the rat, CRF and ethanol significantly augment CeA gamma
      aminobutyric acid (GABA) release, whereas nociceptin diminishes it. METHODS:
      Using electrophysiologic techniques in an in vitro slice preparation, we
      investigated the interaction of nociceptin and CRF on evoked and spontaneous
      GABAergic transmission in CeA slices of naive and ethanol-dependent rats and the
      mechanistic role of protein kinase A. RESULTS: In neurons from naive animals,
      nociceptin dose-dependently diminished basal-evoked GABA(A) receptor-mediated
      inhibitory postsynaptic potentials (IPSPs) by decreasing GABA release and
      prevented, as well as reversed, CRF-induced augmentation of IPSPs, actions that
      required PKA signaling. In neurons from ethanol-dependent animals, nociceptin
      decreased basal GABAergic transmission and blocked the CRF-induced increase in
      GABA release to a greater extent than in naive controls. CONCLUSIONS: These data
      provide new evidence for an interaction between the nociceptin and CRF systems in
      the CeA. Nociceptin opposes CRF effects on CeA GABAergic transmission with
      sensitization of this effect in dependent animals. These properties of nociceptin
      may underlie its anti-alcohol and anxiolytic properties and identify the
      nociceptin receptor as a useful therapeutic target for alcoholism.

PMID- 22153591
TI  - Up-to-date concentrations of long-lived artificial radionuclides in the Tom and
      Ob rivers in the area influenced by discharges from Siberian chemical combine.
AB  - The Siberian Chemical Combine (SCC) is located in Seversk (formerly known as
      Tomsk-7) in the Tomsk Region of the Russian Federation. The main contribution of
      radionuclides in the SCC process water discharged into the Tom River was from the
      single-pass reactors, now removed from service (the last SCC reactor was shutdown
      on June 5, 2008). The data on the concentrations of (90)Sr, (137)Cs, (239,240)Pu
      and other artificial radionuclides in water, bottom sediments and flood-plain
      soils of the Tom and Ob rivers from Tomsk to the confluence of the rivers, are
      presented and discussed. The results of measurements carried out after shutdown
      of the last SCC single-pass reactor indicated no radiologically significant
      consequences of SCC activities for the studied water environment compartments.
      Contemporary activity concentrations of long-lived artificial radionuclides (3)H,
      (90)Sr, (137)Cs and (239,240)Pu in river water were below the intervention levels
      established by current regulations of the Russian Federation for these
      radionuclides. The results of (3)H analysis in water from the Tom and Samuska
      rivers demonstrated no inflow of contaminated formation water to surface water
      from the sites where liquid radioactive wastes of the SCC were injected below the
      surface. However, the density of flood-plain soil contamination by long-lived
      (137)Cs in the area influenced by SCC liquid discharges was higher than regional
      technogenic background. There were local flood-plain areas contaminated not only
      by (137)Cs, but also other gamma-emitters, such as (60)Co and (152)Eu.

PMID- 22153592
TI  - Vibrational spectroscopic and quantum chemical calculations of (E)-N
      Carbamimidoyl-4-((naphthalen-1-yl-methylene)amino)benzene sulfonamide.
AB  - FT-IR and FT-Raman spectra of (E)-N-Carbamimidoyl-4-((naphthalen-1-yl
      methylene)amino)benzene sulfonamide were recorded and analyzed. The vibrational
      wavenumbers were computing at various levels of theory. The data obtained from
      theoretical calculations are used to assign vibrational bands obtained
      experimentally. The results indicate that B3LYP method is able to provide
      satisfactory results for predicting vibrational frequencies and structural
      parameters. The calculated first hyperpolarizability is comparable with reported
      values of similar derivatives and is an attractive object for future studies of
      non-linear optics. The geometrical parameters of the title compound are in
      agreement with that of similar derivatives.

PMID- 22153593
TI  - Application of the multi-parameter SQM harmonic force field, and ESFF harmonic
      frequencies scaling procedures to the determination of the vibrational spectra of
      silicon- and sulfur(II)-containing compounds.
AB  - Multi-parameter scaling techniques, such as Scaled Quantum Mechanical (SQM) force
      field [J. Am. Chem. Soc. 105 (1983) 7037-7047; J. Phys. Chem. A 102 (1998) 1412
      1424] or Effective Scaling Frequency Factor (ESFF) [Chem. Phys. Lett. 446 (2007)
      191-198; J. Mol. Spectrosc. 264 (2010) 66-74] techniques, are very powerful in
      the theoretical prediction of the vibrational spectra of complex molecules. In
      the present work sets of transferable SQM and ESFF scaling factors (within the
      valence coordinates based schemes) that can be applied to silicon- and sulfur(II)
      containing compounds have been determined. A number of VDZ- and VTZ-quality basis
      sets were used in conjunction with the B3LYP density functional. Eight molecules
      typically used in the synthesis of silica-based materials were chosen, and
      theoretical modes were assigned to bands detected on their IR or Raman spectra.
      This set was augmented with a set of 10 auxiliary, sulfur(II)-containing
      molecules, for which only "pure" vibrations involving S-containing motifs were
      assigned. This led to the set of more than 600 individual vibrations. Five
      factors attributed to these motifs were optimized. Scaling factors attributed to
      the characteristic types of internal coordinates including the second-row atoms
      and chlorine, which are applicable to the present molecules were preset. Their
      values, optimized for Baker's training set of molecules [J. Phys. Chem. A 102
      (1998) 1412-1424] for all basis sets considered in this work, were also found,
      extending thus the applicability of the multi-parameter scaling methods. New
      scaling factors exhibit low statistical uncertainties. Reasonable agreement
      between experimental and SQM- or ESFF-scaled frequencies was obtained even for
      the 6-31G* basis set (RMS<12cm(-1)); extension of the basis set by adding
      polarization function on hydrogen atoms and/or diffuse functions provides
      significant improvement of the results, for which the RMS values are often (well)
      below 10 cm(-1). In addition, SQM scaling factors were found to occasionally
      exhibit large deviations from unity, which is to be contrasted with ESFF scaling
      factors.

PMID- 22153594
TI  - Molecular structure and vibrational spectroscopic studies of Chrysin using HF and
      Density Functional Theory.
AB  - In the present study, the molecular confirmation, vibrational and electronic
      transition analysis of 5,7-dihyroxyflavone (Chrysin) were investigated using
      experimental techniques (FT-IR, FT-Raman and UV) and quantum chemical
      calculations by HF and DFT/B3LYP method with 6-31G(d,p) as basis set. The FT-IR
      and FT-Raman spectra in solid phase were recorded in the region 4000-400cm(-1)
      and 3500-50cm(-1) respectively. The UV absorption spectra of the title compound
      dissolved in water, methanol and ethanol were recorded in the range of 200-400nm.
      The complete vibrational assignments were performed on the basis of total energy
      distribution (TED) of the vibrational modes, calculated with scaled quantum
      mechanic (SQM) method. By using TD-DFT calculation, electronic absorption spectra
      of the title compound have been predicted and a good agreement with experimental
      one is established. In addition, the molecular electrostatic potential (MEP),
      natural bond orbital (NBO) analysis have been investigated using theoretical
      calculations. The calculated HOMO and LUMO energies show that charge transfer
      occurs within the molecule.

PMID- 22153595
TI  - Light-emitting materials from cyclometalated heteroleptic iridium(III) complexes-
      A physicochemical study.
AB  - Phosphorescent studies of 2-arylimidazole heteroleptic cyclometalated
      iridium(III) complexes with picolinic acid as the ancillary ligand were made. The
      observed experimental data reveal that these complexes possess dominantly (3)MLCT
      and (3)pi-pi* excited states and the solvent shift of these complexes is
      interpreted by Reichardt-Dimroth and Marcus solvent functions. The results are
      consistent with prior assignments on the absorption band to a metal-to-ligand
      charge transfer excited state associated with chelating ligand. Emission kinetic
      studies exploited that the radiative transition (k(r)) increases with increasing
      lambda(em).

PMID- 22153596
TI  - A novel and efficient method for the immobilization of thermolysin using sodium
      chloride salting-in and consecutive microwave irradiation.
AB  - Sodium chloride salting-in and microwave irradiation were combined to drive
      thermolysin molecules into mesoporous support to obtain efficiently immobilized
      enzyme. When the concentration of sodium chloride was 3 M and microwave power was
      40 W, 93.2% of the enzyme was coupled to the support by 3 min, and the maximum
      specific activity of the immobilized enzyme was 17,925.1 U mg(-1). This was a 4.5
      fold increase in activity versus enzyme immobilized using conventional
      techniques, and a 1.6-fold increase versus free enzyme. Additionally, the thermal
      stability of the immobilized thermolysin was significantly improved. When
      incubated at 70 degrees C, there was no reduction in activity by 3.5h, whereas
      free thermolysin lost most of its activity by 3h. Immobilization also protected
      the thermolysin against organic solvent denaturation. The microwave-assisted
      immobilization technique, combined with sodium chloride salting-in, could be
      applied to other sparsely soluble enzymes immobilization because of its
      simplicity and high efficiency.

PMID- 22153597
TI  - Transformation of (+/-)-lavandulol and (+/-)-tetrahydrolavandulol by a fungal
      strain Rhizopus oryzae.
AB  - Biotransformation of an irregular monoterpene alcohol, (+/-)-lavandulol [(+/-)-5
      methyl-2-(1-methylethenyl)-4-hexen-1-ol] (I) and its tetrahydro derivative, (+/-)
      tetrahydrolavandulol [(+/-)-2-isopropyl-5-methylhexan-1-ol] (II) were studied
      using a soil isolated fungal strain Rhizopus oryzae. Five metabolites, 2-((3,3
      dimethyloxiran-2-yl)methyl)-3-methylbut-3-en-1-ol (Ia), 2-methyl-5-(prop-1-en-2
      yl)hex-2-ene-1,6-diol (Ib), 2-methyl-5-(prop-1-en-2-yl)hexane-1,6-diol (Ic), 2-(3
      methylbut-2-enyl)-3-methylenebutane-1,4-diol (Id), 5-methyl-2-(2-methyloxiran-2
      yl)hex-4-en-1-ol (Ie) have been isolated from the fermentation medium and
      characterized with lavandulol as a substrate. When tetrahydrolavandulol used as a
      substrate, two metabolites 2-isopropyl-5-methylhexane-1,5-diol (IIa) and 2
      isopentyl-3-methylbutane-1,3-diol (IIb) have been isolated from the fermentation
      medium. Biotransformation studies with R. oryzae clearly indicate that the
      organism initiates the transformation either by hydroxylation at allylic methyl
      groups or epoxidation of double bond. GC and GCMS analyses indicated that both
      (R)- and (S)-enantiomers of I and II have been transformed into corresponding
      hydroxylated or epoxy derivatives, when racemic I and II were used as substrates.

PMID- 22153598
TI  - Influence of sand layer depth on partial nitritation as pretreatment of
      anaerobically digested swine wastewater prior to anammox.
AB  - This work aimed to investigate the influence of sand layer depth on partial
      nitritation performance as a preparative step for anaerobic ammonium oxidation
      (anammox) process in treating anaerobically digested effluent of swine
      wastewater. A lab-scale biological sand filter system was constructed and partial
      nitritation was successfully maintained with nitrogen loading rate (NLR) of
      approximately 50 g NH(4)(+)-N m(-3) d(-1). An average NH(4)(+)-N removal
      efficiency of 61.34% and conversion efficiency of NH(4)(+)-N to NO(2)(-)-N of
      79.77% were achieved with a sand layer depth of 32 cm. An effluent with a
      NH(4)(+)-N concentration of 242.52 mg L(-1) and a NO(2)(-)-N concentration of
      306.39 mg L(-1) was achieved when the sand layer depth was 32 cm, giving a NO(2)(
      )-N/NH(4)(+)-N ratio close to 1.32, as required by anammox. Overall, using a
      biological sand filter system to treat anaerobically digested effluent of swine
      wastewater by partial nitritation pretreatment prior to anammox is feasible.

PMID- 22153599
TI  - Design and optimization of photo bioreactor for O2 regulation and control by
      system dynamics and computer simulation.
AB  - In this paper, a valid kinetic model of photo bioreactor (PBR) used for highly
      effective cultivation of blue algae, Spirulina platensis, was developed for fully
      describing the dynamic characteristics of O(2) concentration, then a closed-loop
      PBR with Linear-Quadratic Gaussian (LQG) servo controller was established and
      optimized via digital simulation and dynamic response optimization, and the
      effectiveness of the closed-loop PBR was further tested and accredited by real
      time simulation. The result showed that the closed-loop PBR could regulate and
      control the O(2) concentration in its gas phase according to the reference with
      desired dynamic response performance, hence microalgae with unique characteristic
      could be selected as a powerful tool for O(2) regulation and control whenever
      O(2) concentration in Bioregenerative Life Support System (BLSS) deviates from
      the nominal level in emergencies, and greatly enhance safety and reliability of
      BLSS on space and ground missions.

PMID- 22153601
TI  - Amebic colitis in Italy after Christmas.

PMID- 22153603
TI  - Experimental assessment of level pool routing in preliminary design of floodplain
      storage.
AB  - Among control structures in flood management, floodplain storage represents one
      of the most effective measures, since it holds part of flood volume in a
      delimited area thus reducing the peak discharge. Sizing of floodplain storage,
      both on-stream and off-stream, is complex and several methodologies for
      preliminary design are available in literature, almost all assuming level pool
      reservoir routing, i.e. the water level in the floodplain is horizontal during
      the storage filling. Few studies examine the accuracy of that assumption. The
      present paper work reports an extensive experimental investigation to assess the
      reliability of level pool routing in the design of on-stream floodplain storages.
      The good agreement between numerical and experimental values during the filling
      phase confirmed the reliability of the hypothesis in the preliminary sizing of on
      stream floodplain storage. In contrast, even significant differences can be shown
      during the floodplain draining, due to vegetation and bottom irregularities.

PMID- 22153602
TI  - A cross-market cost comparison of erlotinib versus pemetrexed for first-line
      maintenance treatment of patients with locally advanced or metastatic non-small
      cell lung cancer.
AB  - Erlotinib and pemetrexed were approved by the European Medicines Agency for first
      line maintenance treatment of patients with locally advanced or metastatic non
      small-cell lung cancer (NSCLC) to prolong overall survival after first-line
      therapy. An adjusted, matched, indirect comparison of erlotinib and pemetrexed
      suggested that survival benefits were not statistically significantly different
      between treatments. We conducted a cost-comparison analysis of erlotinib versus
      pemetrexed in first-line maintenance treatment of locally advanced or metastatic,
      non-squamous NSCLC in France, Germany, Italy and Spain, performed from the
      perspective of national health-care decision-makers or purchasers. The analysis
      was limited to direct costs and comprised drug-acquisition costs, administration
      costs and costs of treating adverse events (AEs). A one-way sensitivity analysis
      on administration, acquisition and AE costs was also performed. Total monthly per
      patient treatment costs for erlotinib in France, Germany, Italy and Spain were
      ?2140, ?2732, ?1518 and ?2048, respectively, and for pemetrexed ?3453, ?5534,
      ?2921 and ?3164, respectively. AE cost was greater for pemetrexed in all
      countries, as was administration cost. As an oral treatment, erlotinib is not
      associated with any administration costs, except in Germany, where the cost is
      lower than for pemetrexed. The sensitivity analysis showed acquisition costs to
      be the main driver of total monthly per-patient costs. Erlotinib appears to be a
      cost-saving treatment alternative to pemetrexed, producing comparable survival
      benefits, based on an indirect comparison, at a lower cost.

PMID- 22153604
TI  - Electromagnetic hypersensitivity: fact or fiction?
AB  - As the prevalence of wireless telecommunication escalates throughout the world,
      health professionals are faced with the challenge of patients who report symptoms
      they claim are connected with exposure to some frequencies of electromagnetic
      radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of
      hypersensitivity to EMR resulting from common exposures such as wireless systems
      and electrical devices in the home or workplace; others suggest that
      electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various
      organizations including the World Health Organization as well as some nation
      states are carefully exploring this clinical phenomenon in order to better
      explain the rising prevalence of non-specific, multi-system, often debilitating
      symptoms associated with non-ionizing EMR exposure. As well as an assortment of
      physiological complaints, patients diagnosed with EHS also report profound social
      and personal challenges, impairing their ability to function normally in society.
      This paper offers a review of the sparse literature on this perplexing condition
      and a discussion of the controversy surrounding the legitimacy of the EHS
      diagnosis. Recommendations are provided to assist health professionals in caring
      for individuals complaining of EHS.

PMID- 22153605
TI  - Black soiling of an architectural limestone during two-year term exposure to
      urban air in the city of Granada (S Spain).
AB  - A two-year term aging test was carried out on a building limestone under
      different urban conditions in the city of Granada (Southern Spain) to assess its
      Cultural Heritage sustainability. For this purpose stone tablets were placed
      vertically at four sites with contrasting local pollution micro-environments and
      exposure conditions (rain-sheltered and unsheltered). The back (rain-sheltered)
      and the front (rain-unsheltered) faces of the stone tablets were studied for each
      site. The soiling process (surface blackening) was monitored through lightness
      (DeltaL*) and chroma changes (DeltaC*). Additionally atmospheric particles
      deposited on the stone surfaces and on PM10 filters during the exposure time were
      studied through a multianalytical approach including scanning electron microscopy
      (SEM-EDX), transmission electron microscopy (TEM) and micro-Raman spectroscopy.
      The identified atmospheric particles (responsible for stone soiling) were mainly
      soot and soil dust particles; also fly ash and aged salt particles were found.
      The soiling process was related to surface texture, exposure conditions and
      proximity to dense traffic streets. On the front faces of all stones, black
      soiling and surface roughness promoted by differential erosion between micritic
      and sparitic calcite were noticed. Moreover, it was found that surface roughness
      enhanced a feedback process that triggers further black soiling. The calculated
      effective area coverage (EAC) by light absorbing dust ranged from 10.2 to 20.4%,
      exceeding by far the established value of 2% EAC (limit perceptible to the human
      eye). Soiling coefficients (SC) were estimated based on square-root and bounded
      exponential fittings. Estimated black carbon (BC) concentration resulted in
      relatively similar SC for all studied sites and thus predicts the soiling process
      better than using particulate matter (PM10) concentration.

PMID- 22153606
TI  - Temporal changes in elemental composition in decomposing filamentous algae
      (Cladophora glomerata and Pilayella littoralis) determined with PIXE and PIGE.
AB  - Particle-induced X-ray emission and particle-induced gamma-ray emission
      spectrometry were successfully applied in a study of the elemental composition of
      decomposing filamentous algae. Fresh brown (Pilayella littoralis) and green
      (Cladophora glomerata) algal materials were placed in cages at 4m depth in a
      water column of 8m in the Archipelago Sea, northern Baltic Sea. Every second week
      decaying algae were sampled from the cages to allow measurements of changes in
      the elemental compositions. In the study of the elemental losses the
      concentrations were compensated for the mass reduction. The results show that
      sulphur, chlorine and partly potassium were lost during decomposition of P.
      littoralis and C. glomerata. Most of the other elements studied were recovered in
      the remaining algal mass. Special attention was paid to sorption and desorption
      of elements, including metal binding capacity, in the decaying algal materials.
      The affinity order of different cations to the two algal species was established
      by calculation of conditional distribution coefficients, D'(M). For instance for
      P. littoralis the following series of binding strength (affinity) of cations were
      obtained: Al>Ti>Fe >> Mn>Ni, Cu>Ba, Cr, Zn>>Rb>K, Sr>Pb>>Ca>>Na>Mg. Notably is
      that the binding strength of strontium was more than 10 times higher for P.
      littoralis than for C. glomerata. Due to their high binding capacity and good
      affinity and selectivity for heavy metal ions these algae have great potential as
      biological sorbents. Large variations in elemental content during decomposition
      complicate the use of algae for environmental monitoring.

PMID- 22153607
TI  - A study on the atmospheric concentrations of primary and secondary air pollutants
      in the Athens basin performed by DOAS and DIAL measuring techniques.
AB  - In this work an analysis of continuous Differential Optical Absorption
      Spectroscopy (DOAS) measurements of primary and secondary air pollutants (SO(2),
      NO(2) and O(3)) in the Athens basin is performed combined with Differential
      Absorption Lidar (DIAL) vertical ozone measurements obtained inside the Planetary
      Boundary Layer (PBL) and the lower free troposphere. The measurements took place
      during the period May 2005-February 2007, at the National Technical University of
      Athens Campus (200 m above sea level (asl.), 37.96  degrees N, 23.78  degrees E).
      The SO(2) and NO(2) DOAS measurements showed maximum 1-hour mean values (around
      20 MUg/m(3) and 74 MUg/m(3), respectively) in winter and did not exceed the
      current European Union (EU) air quality standards (European Council Directive
      2008/50/EC), in contrast to ozone, which shows its maximum (around 128 MUg/m(3))
      in summer and frequently exceeds the EU standard for human health protection (120
      MUg/m(3)). If the measurements are classified according to the two most frequent
      flow-patterns of the air masses in the Athens basin (northern-southern
      circulation), it is observed that in general the atmospheric concentrations of
      all measured pollutants including ozone are higher when the southern circulation
      occurs, in comparison to the corresponding values under the northern circulation.
      The vertical ozone profiles obtained by DIAL were also higher under the southern
      circulation. During the summer months a mean difference (between the southern
      northern circulations) of the order of 15-20 MUg/m(3), maximized at the 0.9-1.1
      km and 1.7-1.8 km height, was observed within the PBL. It was also observed that
      the summer surface ozone levels remained relatively high (around 80-110 MUg/m(3))
      even during strong northerly winds, verifying the high levels of rural surface
      ozone in the surrounding area reported by previous studies.

PMID- 22153608
TI  - Coordinating developmental signaling: novel roles for the Hippo pathway.
AB  - Genetic and biochemical studies have defined the Hippo pathway as a central
      mediator of developmental and pathogenic signals. By directing intracellular
      signaling events, the Hippo pathway fine-tunes cell proliferation, cell death,
      and cell-fate decisions, and coordinates these cues to specify animal organ size.
      Recent studies have revealed that Hippo pathway-mediated processes are
      interconnected with those of other key signaling cascades, such as those mediated
      by TGF-beta and Wnt growth factors. Moreover, several reports have described a
      role for cell contact-mediated polarity proteins in Hippo pathway regulation.
      Emerging details suggest that crosstalk between these signals drives fundamental
      developmental processes, and deregulated intercellular communication influences
      disease progression, such as cancer. We review recent data with a focus on how
      the Hippo pathway integrates its activity with other signaling pathways.

PMID- 22153609
TI  - Assessment of clinicopathological characteristics and immunoexpression of COX-2
      and IL-10 in oral pyogenic granuloma.
AB  - OBJECTIVE: The aim was to investigate the relationship between patient clinical
      background, histological features, and immunoexpression of COX-2 and IL-10 in
      oral pyogenic granuloma (PG). DESIGN: Paraffin-embedded samples of oral PG (n=57)
      were prepared for histological and immunohistochemical assessment. Based on the
      histological features, the samples were categorised into lobular capillary
      hemangioma (LCH) and non-LCH subtypes. The epithelial lining, angiogenic index,
      inflammatory infiltrate density, and interstitial fibrosis, were assessed in
      haematoxylin-eosin stained sections. In addition, the marker expression
      estimation (stained cells/total cell number) was used to assess immunoreactivity
      for each sample. RESULTS: Although there were no significant differences between
      histological subtypes regarding demographic and clinical parameters, mean values
      of microvessel count and inflammatory infiltrate density were significantly
      greater in the non-LCH PG subtype. Also, whilst cellular immunolocalisation
      patterns of COX-2 and IL-10 were similar, mean values of expression estimation of
      each immunomarker were significantly higher in non-LCH PGs in comparison with LCH
      subtypes. Furthermore, significant variations for immunohistochemical parameters
      were evident regarding to angiogenic index and inflammatory infiltrate density,
      but not concerning demographic and clinical data. Finally, linear regression
      analysis showed a significant positive correlation between the expression
      estimation of the two immunomarkers. CONCLUSION: These findings suggest a role
      for COX-2 and IL-10 in the etiopathogenesis of oral PG and indicate that LCH and
      non-LCH histological subtypes represent different stages in the evolution of a
      single lesion with varying degrees of proliferative, angiogenic, and inflammatory
      activity.

PMID- 22153610
TI  - Places in the dental arch that show a greater variability in tooth number, shape
      and position--a prevalence study.
AB  - OBJECTIVE: The aim of this study was to assess the frequency of variations in
      tooth number, shape and position in the dental arch to determine if there are
      parts of the dental arch that show a higher prevalence of tooth variability.
      DESIGN: 198 randomly selected Caucasian subjects (93 females, 105 males) aged
      between 10.0 and 24.5 years (mean age 14.15, SD 2.34 years) were included. A
      total of 5544 teeth were examined and dental anomalies of tooth number, shape and
      position (oral teeth positions and teeth rotations greater than 45 degrees ) were
      recorded. RESULTS: 18.68 per cent of the subjects had one or more unerupted
      teeth. Aplasia as the cause of uneruption was found in 12.12 per cent of the
      subjects, statistically significantly more frequently in females than males
      (Fisher test, p < 0.05). Tooth shape anomalies were found in 6.57 per cent of the
      sample, more frequently in males than females (Fisher test, p < 0.05). Oral
      position of one or more teeth was found in 47.98 per cent of the sample, whilst
      rotations greater than 45 degrees  were found in 15.66 per cent, with no
      statistically significant differences between females and males. One or more of
      the observed dental anomalies were found in several tooth types, however all the
      observed dental anomalies were found only in second premolars and in upper
      lateral incisor. CONCLUSIONS: According to the results of this study, it seems
      that some places in the dental arch show a greater variability in terms of tooth
      number, shape and position. This could be a result of genetic and environmental
      influences during odontogenesis or a result of evolutionary trends.

PMID- 22153611
TI  - Effect of adding essential oils of coriander (Coriandrum sativum L.) and hyssop
      (Hyssopus officinalis L.) on the shelf life of ground beef.
AB  - This study examined the effect of adding essential oils of hyssop and coriander
      at the highest concentration (0.02% v/w) sensorially acceptable to a panel of
      assessors on the microbiological and biochemical characteristics of stored ground
      beef. Vacuum-packed meat was stored at 0.5+/-0.5 degrees C and 6+/-1 degrees C
      for 15days. The greatest beneficial effect of both additives was in inhibiting
      the development of undesirable sensory changes (extending acceptability by up to
      3days) and the growth of Enterobacteriaceae (by up to approximately 1-2 log
      cycles compared with the controls). The effect on lactic acid bacteria, total
      viable bacterial count and other groups of microorganisms investigated was minor
      (up to 1 log cycle) and similar for both oils. Neither did these additives
      significantly affect amino nitrogen levels, protease activity, the proportions of
      meat pigments, protein electropherograms and pH levels. This indicates the
      limited effect of these essential oils in the concentrations applied on
      preserving vacuum-packed minced beef.

PMID- 22153612
TI  - Analysis of antibiotic resistance patterns and detection of mecA gene in
      Staphylococcus aureus isolated from packaged hamburger.
AB  - Presence of Staphylococcus aureus, antibiotic resistance pattern and PCR
      detection of mecA gene in isolated strains were investigated in total of 256
      packaged hamburgers in Iran-Tehran. For this purpose we used standard disk
      diffusion method and sensitive and specific PCR technique, respectively. Results
      showed that 25% of samples were positive for S. aureus. Resistance to meticillin,
      erythromycin, penicillin G, cefazolin, ciprofloxasin, vacomycin and amoxiclave
      was determined 89%, 20.3%, 18.7%, 15.6%, 14%, 26.6% and 12.5%, respectively.
      According to the obtained results from PCR analysis of methicillin-resistant S.
      aureus (MRSA), mecA gene was present in 100% of the resistant isolates, 0% of
      intermediate-resistance isolates and 25% of susceptible isolates. The results
      obtained from PCR detection of mecA gene showed high correlation with standard
      disk diffusion test.

PMID- 22153613
TI  - Balanced autosomal translocation and double Robertsonian translocation in cases
      of primary amenorrhea in an Indian population.
AB  - OBJECTIVE: To assess the frequency of balanced autosomal translocations in
      patients with primary amenorrhea in an Indian population. METHODS: Cytogenetic
      analysis was carried out among women referred from all parts of India for primary
      amenorrhea between 2002 and 2010. Clinical history and laboratory findings were
      taken into consideration to determine the diagnosis. G-banding with trypsin
      Giemsa was performed to detect chromosome abnormalities. RESULTS: There were 15
      balanced autosomal translocations in 1100 patients. Two novel translocations were
      identified: 1 with mosaic pattern of X chromosome monosomy and male karyotype,
      together with balanced autosomal translocation of chromosomes 11 and 20 in both
      cell lines; and 1 with double Robertsonian translocation of chromosomes 14 and
      21. CONCLUSION: Autosomal genes have a crucial role in reproductive development.
      More candidate genes need to be recognized for appropriate genetic counseling and
      clinical management.

PMID- 22153614
TI  - Pelvic splenosis in an infertile patient.

PMID- 22153615
TI  - Muscle-derived stem cells and smooth muscle healing in a rat model of uterine
      injury.

PMID- 22153616
TI  - Lack of independent prognostic and predictive value of centromere 17 copy number
      changes in breast cancer patients with known HER2 and TOP2A status.
AB  - The clinical benefit of anthracyclines has been connected to HER2 status, TOP2A
      status and centromere 17 copy numbers (CEN-17). Data from a clinical trial
      randomizing patients to anthracyclines was used to assess whether the number of
      CEN-17 in breast cancers may predict incremental responsiveness to anthracyclines
      besides what is obtained when used relatively to TOP2A and HER2. As cut sections
      of paraffin-embedded tissue are prone to truncation of nuclei, strict definition
      of ploidy levels is lacking. We therefore used normal breast tissue to assist
      define ploidy levels in cut sections. Fluorescence in situ hybridization (FISH)
      with centromere 17 (CEN-17) and TOP2A was performed on 120 normal breast
      specimens. The diploid CEN-17 copy number was reduced from the expected two
      signals in whole nuclei to an average of 1.68 signals per nucleus in cut sections
      of normal breast. Ploidy levels determined in normal breast were applied to data
      on 767 patients with known HER2 and TOP2A status randomized to anthracyclines in
      the DBCG 89D trial. CEN-17 ploidy levels were in cut sections from the 767 breast
      cancer patients established as: Haploid: <=1.25 (10%), diploid: 1.26-2.09 (60%),
      triploid: 2.10-2.93 (21%), tetraploid: 2.94-3.77 (5%) or higher ploidy: >=3.78
      (4%). Amplification of HER2 and deletion of TOP2A were frequently observed in
      tumors with a high ploidy level. In univariate analyses increasing ploidy was
      associated with decreased disease-free survival (DFS) (P=0.0001) and overall
      survival (OS) (P<0.0001). However, in multivariate analysis CEN-17 was not
      established as an independent prognostic factor and was neither a statistically
      significant predictor of benefit from CEF (Cyclophosphamide/Epirubicin/5
      Fluorouracil) compared to CMF (Cyclophosphamide/Methotrexate/5-Fluorouracil)
      (P(Interaction) 0.39 for DFS and 0.67 for OS). In conclusion, CEN-17 levels do
      not independently from TOP2A/CEN-17 ratio identify breast cancer patients who
      achieve an incremental benefit from adjuvant anthracyclines.

PMID- 22153619
TI  - Intrapulmonary effects of setting parameters in portable intrapulmonary
      percussive ventilation devices.
AB  - BACKGROUND: Despite potential benefits of intrapulmonary percussive ventilation
      (IPV) in various respiratory diseases, the impact of setting parameters on the
      mechanical effects produced by IPV in the lungs is unknown. We hypothesized that
      changing the parameters on IPV would modulate  these effects. This in vitro study
      aimed at comparing the changes in intrapulmonary effects resulting from changes
      in parameters in 3 portable IPV devices (IMP2, Impulsator, and Pegaso). METHODS:
      Parameters were set in 72 combinations of frequency (90-250 cycles/min),
      inspiratory to  expiratory (I/E) time ratio (from 1/2 to 3/1), and pressure (10
      60 cm H(2)O). Four resulting effects were recorded on a test lung via a
      pneumotachometer: the expiratory to inspiratory flow ratio (E/I flow ratio), the
      PEEP, the ventilation, and the percussion. Percussion was  assessed by the end
      slope of the pressure curve. Analysis of variance was used for data analysis.
      RESULTS: E/I flow ratio increased with increasing I/E time ratio (P < .001). The
      Pegaso produced the lowest E/I flow ratio. PEEP raised 6 cm H(2)O in both IMP2
      and Impulsator,  and 17 cm H(2)O in the Pegaso with increasing frequency (P <
      .01), pressure, and I/E time ratio (P < .001). In all devices, ventilation
      increased with increasing pressure and decreasing frequency (P < .001).
      Percussion increased with increasing frequency  and decreasing I/E time ratio (P
      < .001), and with increasing pressure when I/E time ratio was 1/1 or less. The
      Pegaso provided the poorest percussion. CONCLUSIONS: This study suggests that
      changing the parameters considerably modulates the mechanical effects produced by
      portable  IPV devices in the lungs. Increasing frequency increased PEEP and
      percussion, but decreased ventilation. Increasing I/E time increased PEEP and E/I
      flow ratio, and decreased percussion. Finally, increasing pressure increased PEEP
      and ventilation. The Pegaso produced the highest PEEP, least  percussion, and
      smallest change in E/I flow ratio.

PMID- 22153617
TI  - CRABP-II methylation: a critical determinant of retinoic acid resistance of
      medulloblastoma cells.
AB  - Medulloblastoma cells exhibit varied responses to therapy by all-trans retinoic
      acid (RA). The underlying mechanism for such diverse effects however remains
      largely unclear. In this study, we attempted to elucidate the molecular basis of
      RA resistance through the study of RA signaling components in both RA-sensitive
      (Med-3) and RA-resistant (UW228-2 and UW228-3) medulloblastoma cells. The results
      revealed that RARalpha/beta/gamma and RXRalpha/beta/gamma were found in the three
      cell lines. Expression of CRABP-I and CRABP-II was seen in Med-3 cells, up
      regulated when treated with RA, but was absent in UW228-2 and UW228-3 cells
      regardless of RA treatment. Bisulfite sequencing revealed 8 methylated CG sites
      at the promoter region of CRABP-II in UW228-2 and UW228-3 but not in Med-3 cells.
      Demethylation by 5-aza-2'-deoxycytidine recovered CRABP-II expression. Upon
      restoration of CRABP-II expression, both UW228-2 and UW228-3 cells responded to
      RA treatment by forming neuronal-like differentiation, synaptophysin expression,
      beta-III tubulin upregulation, and apoptosis. Furthermore, CRABP-II specific
      siRNA reduced RA sensitivity in Med-3 cells. Tissue microarray-based
      immunohistochemical staining showed variable CRABP-II expression patterns among
      104 medulloblastoma cases, ranging from negative (42.3%), partly positive (14.4%)
      to positive (43.3%). CRABP-II expression was positively correlated with
      synaptophysin (rs = 0.317; p = 0.001) but not with CRABP-I expression (p > 0.05).
      In conclusion, aberrant methylation in CRABP-II reduces the expression of CRABP
      II that in turn confers RA resistance in medulloblastoma cells. Determination of
      CRABP-II expression or methylation status may enable a personalized RA therapy in
      patients with medulloblastomas and other types of cancers.

PMID- 22153620
TI  - Chemical enhancement of soil based footwear impressions on fabric.
AB  - This study investigates the enhancement of footwear impressions prepared with
      soils from different locations on a variety of fabric surfaces with different
      morphology. Preliminary experiments using seventeen techniques were carried out
      and the best responding reagents were evaluated further. Results indicated that
      the soils investigated (a cross-section of soils from Scotland) are more likely
      to respond to reagents that target iron ions rather than calcium, aluminium or
      phosphorus ions. Furthermore, the concentration of iron and soil pH did not
      appear to have an effect on the performance of the enhancement techniques. For
      the techniques tested, colour enhancement was observed on all light coloured
      substrates while enhancement on dark coloured fabrics, denim and leatherette was
      limited due to poor contrast with the background. Of the chemical enhancement
      reagents tested, 2,2'-dipyridil was a suitable replacement for the more common
      enhancement technique using potassium thiocyanate. The main advantages are the
      use of less toxic and flammable solvents and improved clarity and sharpness of
      the enhanced impression. The surface morphology of the fabrics did not have a
      significant effect on the enhancement ability of the reagents apart from a slight
      tendency for diffusion to occur on less porous fabrics such as polyester and
      nylon/lycra blends.

PMID- 22153618
TI  - Down-regulation of tumor suppressor MTUS1/ATIP is associated with enhanced
      proliferation, poor differentiation and poor prognosis in oral tongue squamous
      cell carcinoma.
AB  - Microtubule-associated tumor suppressor gene (MTUS1, also known as mitochondrial
      tumor suppressor) is a recently identified tumor suppressor gene that has been
      implicated in several cancer types. The expression of MTUS1 gene leads to 5 known
      transcript variants and codes for 5 isoforms of Angiotensin II AT2 receptor
      interacting protein (ATIP). In this study, we first confirmed that the down
      regulation of MTUS1/ATIP was a frequent event in oral tongue squamous cell
      carcinoma (OTSCC) and the premalignant lesion (leukoplakia). We further
      demonstrated that the down-regulation of MTUS1/ATIP was correlated with poor
      differentiation and enhanced proliferation (Ki67 proliferation index).
      Statistical analysis suggests that the down-regulation of MTUS1/ATIP was
      associated with reduced overall survival. Isoform specific quantitative RT-PCR
      assays revealed that ATIP1, ATIP3a and ATIP3b were the major isoforms of the
      MTUS1 gene products in oral tongue epithelial cells. Significant down-regulations
      were observed for all 3 ATIP isoforms in OTSCC as compared to matching normal
      tissues. In vitro functional study showed that the restoration of ATIP1
      expression led to G1 arrest, apoptosis and reduction of cell proliferation in
      OTSCC cell lines. These ATIP1-induced cellular changes were accompanied by
      reduced phosphorylation of ERK1/2 and up-regulation of p53. Taken together, these
      data suggest that MTUS1 plays major roles in the progression of OTSCC, and may
      serve as a biomarker or therapeutic target for patients with OTSCC.

PMID- 22153621
TI  - Age assessment by magnetic resonance imaging of the knee: a preliminary study.
AB  - The authors developed an original magnetic resonance imaging (MRI) staging system
      for epiphyseal fusion of growth plate maturation of the knee and evaluated its
      reliability and validity for age assessment of living individuals. A total of 290
      MRI scans of the knee were reviewed retrospectively in patients aged from 10 to
      30 years old (138 males, 152 females). Five original MRI stages were defined to
      assess the degree of maturation of the distal femoral and proximal tibial
      epiphyses. Intra-observer variability was excellent and inter-observer
      variability was good, demonstrating the reliability and the validity of this
      original MRI staging system. In both sexes, the changes of growth plates
      (proximal tibial or distal femoral) were associated with age (p<0.001). Our
      results agreed with classic data on skeletal maturation of the knee, with
      globally earlier maturation in females than in males, and also earlier maturation
      of the proximal tibial epiphysis than of the distal femoral epiphysis. MRI of the
      knee is an efficient non-invasive method of age assessment, without the
      disadvantage of X-ray exposure. Further studies with larger groups are needed to
      support our results.

PMID- 22153622
TI  - Determination of impurities in illicit methamphetamine samples seized in Iran.
AB  - In this study fifty samples of crystalline methamphetamine obtained from
      antinarcotics police of Iran seized during the year 2010 were analyzed. In order
      to determine the chemical characteristics of these samples, anion test, Gas
      Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass
      Spectrometry (LC-MS) were carried out on the samples. All of the samples
      containing methamphetamine tested positive for chloride anion. The range of
      methamphetamine hydrochloride content in these samples was 33-95%. One sample out
      of 50 contained no methamphetamine. The fact that 1,2-dimethyl-3-phenylaziridine
      was the most frequently found impurity in the analyzed samples, indicates that
      most of the methamphetamine samples seized in Iran have been synthesized from
      pseudoephedrine as starting material.

PMID- 22153623
TI  - Radiation-induced blood-brain barrier damages: an in vitro study.
AB  - A radiation-induced blood-brain barrier (BBB) breakdown has been supposed to
      explain the acute radiation syndrome and the delayed brain radiation injury, but
      it has been clearly demonstrated only at high doses. In a previous study (Diserbo
      et al., 2002), we showed that non-lethal total body irradiation produced an early
      transient increase in BBB permeability in rats but the underlying mechanisms of
      radiation-induced BBB breakdown remain unclear. In the present work, the effects
      of ionizing radiation were studied on an in vitro BBB model. Gamma irradiation
      induced an increase in [(14)C]-sucrose BBB permeability that can be detected 72 h
      after exposure at doses up to 4 Gy. This increase was more important 8 days after
      irradiation and could be limited by dexamethasone treatment. An increase in
      fluorescein and FITC-dextrans (4 kDa/70 kDa) permeability was also observed,
      which can be related to a substantial opening of endothelial cell tight-junctions
      but without massive modification of tight-junction protein (ZO-1, ZO-2, claudin
      5, occludin) immunolabeling even 8 days after 25 Gy exposure. Formation of actin
      stress fibers occurred in endothelial cells 8 days after 25 Gy exposure. A
      progressive decrease in cellular density associated with a simultaneous spreading
      of the endothelial cells was also observed after irradiation. Anti-gammaH2AX
      immunolabeling was used to investigate both DNA double-strand break induction and
      repair rates in endothelial cells. It revealed long-lasting DNA double-strand
      breaks after gamma irradiation. A better understanding and awareness of these
      phenomena are essential for designing appropriate pharmacotherapy in radiation
      therapy and treatment of accidental overexposure.

PMID- 22153624
TI  - alpha-Synuclein synaptic pathology and its implications in the development of
      novel therapeutic approaches to cure Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by a progressive loss of dopamine (DA)
      neurons of the nigrostriatal system and by the presence of Lewy bodies (LB),
      proteinaceous inclusions mainly composed of filamentous alpha-synuclein
      aggregates. Alpha-synuclein is a natively unfolded protein which plays a central
      role in the control of dopaminergic neuronal functions and which is thought to be
      critically implicated in PD pathophysiology. Indeed, besides the fact that alpha
      synuclein is the main protein component of LB, genetic studies showed that
      mutations and multiplications of the alpha-synuclein gene are responsible for the
      onset of familial forms of PD. A large body of evidence indicates that alpha
      synuclein pathology at dopaminergic synapses may underlie the onset of neuronal
      cell dysfunction and degeneration in the PD brain. Thus, since the available
      therapeutic approaches to cure this disease are still limited, we hypothesized
      that the analysis of the alpha-synuclein synaptic proteome/lipidome may represent
      a tool to identify novel potential therapeutic targets to cure this disorder. We
      thus performed a critical review of studies describing alpha-synuclein
      pathophysiology at synaptic sites in experimental models of PD and in this paper
      we outline the most relevant findings regarding the specific modulatory effects
      exerted by alpha-synuclein in the control of synaptic functions in physiological
      and pathological conditions. The conclusions of these studies allow to single out
      novel potential therapeutic targets among the alpha-synuclein synaptic partners.
      These targets may be considered for the development of new pharmacological and
      gene-based strategies to cure PD.

PMID- 22153625
TI  - Managing antiplatelet therapy during ophthalmic procedures: communication is the
      key.

PMID- 22153626
TI  - Genetic factors and AMD.

PMID- 22153627
TI  - Interprofessional collaboration on glaucoma care.

PMID- 22153628
TI  - Model of interprofessional collaboration in the care of patients with glaucoma
      and those suspected of having glaucoma.

PMID- 22153629
TI  - A model of interprofessional collaboration in glaucoma care.

PMID- 22153630
TI  - Taking on glaucoma care as an interprofessional team.

PMID- 22153631
TI  - Prognostic associations of insulin-like growth factor-1 receptor in primary uveal
      melanoma.
AB  - OBJECTIVE: To study the association between immunoreactivity for insulin-like
      growth factor-1 receptor (IGF-1R) in primary ciliary body and choroidal melanoma
      and metastatic death in a consecutive, population-based data set. DESIGN:
      Retrospective, consecutive, population-based cohort study. PARTICIPANTS: A total
      of 167 patients with choroidal and ciliary body melanoma, enucleated from 1972 to
      1981, with long-term survival data. METHODS: Specimens were immunostained by
      using the avidin-biotinylated peroxidase complex method and polyclonal antibodies
      to IGF-1R. The percentage of tumour area that was immunopositive was recorded.
      Survival was assessed by Cox multivariate regression analysis. RESULTS: The
      tumour area could be reliably measured from 129 (78%) of the 167 choroidal or
      ciliary body melanomas. More heavy pigmentation (p = 0.001), larger number of
      macrophages (p = 0.003) and higher microvascular density (p = 0.060) were
      associated with a higher percentage of tumour area that was immunopositive for
      IGF-1R, the reverse being true of extrascleral extension (p = 0.049). No
      significant association was observed with ciliary body extension, largest basal
      tumour diameter, cell type, mean diameter of the 10 largest nucleoli, and
      presence of extravascular matrix loops and networks (p = 0.61-0.96). The
      percentage of tumour area that was immunopositive for IGF-1R was not associated
      with survival. CONCLUSIONS: In our data set, immunoreactivity for IGF-IR did not
      independently predict metastasis from primary uveal melanoma. Partial loss of
      antigenicity can not be ruled out as a confounding factor because no frozen
      sections were available. Results of previous studies have likewise been variable,
      suggesting that immunohistochemical determination of IGF-1R from formalin-fixed,
      paraffin-embedded specimens is not practical as a routine test.

PMID- 22153632
TI  - When straight eyes won't move: phenotypic overlap of genetically distinct ocular
      motility disturbances.
AB  - OBJECTIVE: To describe the phenotypic similarity in a series of patients with
      genetically distinct ocular motility disturbances involving straight eyes and
      different ocular motor pathology. DESIGN: Retrospective case series.
      PARTICIPANTS: Clinical and genetic evaluation of 5 patients with straight eyes in
      the primary position and abnormalities of ocular motility. RESULTS: Patients with
      oculopharyngeal muscular dystrophy, congenital myasthenic syndrome, congenital
      fibrosis of the extraocular muscles type 3, Bosley-Salih-Alorainy syndrome, and
      horizontal gaze palsy and progressive scoliosis all had straight eyes in primary
      position and restricted ocular motility. History, ocular motility patterns,
      systemic features of individual syndromes, and genetic screening were important
      diagnostically. CONCLUSIONS: A number of congenital and genetic ocular motility
      syndromes may result in substantial phenotypic overlap, particularly when eyes
      are straight in primary position and nonophthalmologic features are not apparent
      or not observed. The range of disorders that may fall into this category is
      discussed.

PMID- 22153633
TI  - Predicting retinal tears in posterior vitreous detachment.
AB  - OBJECTIVE: The purpose of this study is to determine whether patients with acute
      posterior vitreous detachment (PVD) who develop delayed retinal tears within the
      first 6 weeks after initial presentation have predictive characteristics. DESIGN:
      Prospective cohort study. PARTICIPANTS: All patients presenting to the Hotel Dieu
      Hospital Emergency Eye Clinic between September 2008 and July 2009 diagnosed with
      acute PVD were offered enrollment. METHODS: At the initial visit, patients were
      given the previously validated Queen's University Posterior Vitreous Detachment
      Patient Diary to record their daily symptoms for 6 weeks. Two or 6 weeks later,
      patients were reexamined in detail, and their diaries were collected and
      analyzed. Exact logistic regression was used to establish characteristics
      predictive of delayed retinal tears. RESULTS: In our study population of 99
      patients, 2 developed delayed retinal tears. One had retinal hemorrhages and the
      other had a cloud-like floater at initial presentation. Vitreal or retinal
      hemorrhage, large number of floaters at initial presentation, and high floater
      frequency at initial presentation indicated a high risk of delayed retinal tear
      formation, yielding a median unbiased estimated odds ratio of 36.18 with p value
      0.009. No other presenting risk factors or symptomatology followed daily over the
      first 6 weeks after acute PVD were predictive of delayed retinal tear formation.
      CONCLUSIONS: PVD patients with retinal or vitreal hemorrhage, a significant
      number of floaters or a cloud like appearance to the floaters, or high floater
      frequency are at higher risk of developing delayed retinal tears.

PMID- 22153634
TI  - Recurrence of macular edema in retinal vein occlusions after treatment with
      intravitreal ranibizumab (Lucentis).
AB  - OBJECTIVE: To evaluate the recurrence of macular edema (ME) in a mixed group of
      patients with branch (BRVO) and central (CRVO) retinal vein occlusion after early
      onset treatment with intravitreal injections of ranibizumab. DESIGN:
      Nonrandomized, uncontrolled prospective clinical trial. PARTICIPANTS: Forty
      patients were enrolled in our study. Twenty-two patients had BRVO and 18 patients
      had CRVO. METHODS: All patients had a minimum follow-up of 12 months. All
      patients had fundus fluorescein angiography (FFA) and optical coherence
      tomography (OCT) at presentation. The time period between RVO occurrences and
      initial examination and treatment was <1 month. Every patient was treated with 2
      consecutive intravitreal injections of ranibizumab (0.5 mg) 1 month apart.
      Assessment was carried out on a monthly basis and injection was carried out if
      necessary, based on OCT findings. RESULTS: Recurrence of ME occurred in 13
      patients (13/22, 59%) in the BRVO group, whereas in the CRVO group occurred in
      all patients (18/18, 100%). Mean time interval of these recurrences from last
      injection was 2.4 months and 1.2 months for BRVO and CRVO groups, respectively.
      Mean period of ME reabsorption was 2.5 months for the BRVO group and 3.5 months
      for the CRVO group. CONCLUSIONS: Recurrent ME occurred in 77.5% of our patients.
      These recurrences occurred sooner, were more prominent and lasted longer in
      patients with CRVO.

PMID- 22153635
TI  - Macular structure on optical coherence tomography after lamellar macular hole
      surgery and its correlation with visual outcome.
AB  - OBJECTIVE: To report macular structure on optical coherence tomography (OCT)
      after lamellar macular hole surgery and its relationship with visual outcome.
      DESIGN: Retrospective interventional case series; private practice setting.
      PARTICIPANTS: Twelve patients diagnosed with a lamellar hole who had undergone
      vitrectomy and who had OCT scanning before and after surgery and at least 6
      months follow-up were included. METHODS: Surgery consisted of 25 g vitrectomy,
      peeling of epiretinal and internal limiting membrane, fluid/air/gas exchange, and
      2 weeks of face-down positioning. RESULTS: OCT showed an epiretinal membrane in
      all cases. After a mean follow-up of 16.7 months, VA improved by >=2 lines in
      nine patients and remained stable in three. There was a complete closure of the
      lamellar hole in ten patients; in four a retinal pseudocyst was found during the
      healing process, resolving spontaneously in two and persisting in the other two
      after 8 and 9 months, respectively. Two patients developed a full-thickness
      macular hole that closed successfully after surgical repair. All patients had a
      VA >= 20/32 at the end of follow-up. CONCLUSION: Epiretinal membranes appear to
      have a role in the pathogenesis of lamellar macular holes. Vitrectomy is a useful
      technique to obtain closure of the lamellar hole and visual improvement. The
      presence of a retinal pseudocyst is a common feature during the healing process
      and is compatible with a favorable visual outcome. A full-thickness macular hole
      is a severe and not uncommon complication of this procedure.

PMID- 22153636
TI  - Spectral domain optical coherence tomography findings in acute retinal pigment
      epitheliitis.
AB  - OBJECTIVE: To report spectral domain optical coherence tomography (SD-OCT)
      findings in 3 patients with acute retinal pigment epitheliitis (ARPE). DESIGN:
      Retrospective chart review. METHODS: Charts of three young patients with ARPE
      were reviewed. RESULTS: In acute stage, SD-OCT demonstrated abnormal
      hyperreflectivity involving the photoreceptor outer segment layer and
      hyporeflectivity involving the associated RPE layer in all cases. In chronic
      stage, SD-OCT showed decreased abnormal reflectivity. In one case with incomplete
      recovery of visual acuity, disruption of the photoreceptor inner and outer
      segment (IS/OS) junction was demonstrated in chronic phase. CONCLUSIONS: SD-OCT
      confirmed that the outer segments of foveal photoreceptors and the associated RPE
      layer were the primary affected sites with ARPE. Detection of integrity of the
      foveal IS/OS line in resolved ARPE could be helpful in prediction of visual
      prognosis.

PMID- 22153637
TI  - Slipped, severed, torn and lost extraocular muscles.
AB  - Slipped, severed, torn and lost extraocular muscles (EOM) are infrequently
      encountered in clinical practice but constitute significant complications of
      strabismus and other eye surgery and of orbital injuries. Knowledge of the
      clinical aspects of these various disease entities and their anatomical
      underpinnings are of utmost importance in providing effective recognition and
      treatment. These conditions share some common presenting signs, symptoms and
      clinical findings that are discussed in this review. The literature will be
      reviewed and management strategies will be presented.

PMID- 22153638
TI  - Error of calibration in ophthalmic calipers: a source of significant clinical
      errors.
AB  - OBJECTIVE: Length measuring instruments are frequently used in ophthalmic surgery
      practice. For all subspecialties, calipers need to be accurate. This study was
      carried out to identify errors of calibration in ophthalmic calipers as a
      potential source of significant clinical errors. DESIGN: This study is a
      descriptive research. METHODS: All Castroviejo calipers free of any visible
      damage and available to the ophthalmic surgeons in the operating room suites of
      our 2 affiliated hospitals were included. The caliper scale readings were
      compared to measurement markings on a standardized ruler at screening points of
      1, 5, 10, and 15 mm on the ruler. Any caliper with a discrepancy of 0.5 mm or
      more at any set of these screening points went on to having further analysis.
      RESULTS: Seventy-one calipers were examined, of which 30 (42%) showed at least 1
      caliper scale reading discrepancy of >=0.5 mm as compared to ruler measurements.
      Errors of at least 1 mm were found in 6 of 30 calipers (20%). The majority of
      calipers underestimated lengths 22/30 (73%), whereas 27% overestimated.
      CONCLUSIONS: With close to half of the calipers inducing a 0.5 mm or more error,
      and with 20% of these at least 1 mm, significant clinical consequences could
      ensue: for example, in follow up of glaucomatous corneas in children, in
      measurements for anterior chamber intraocular lens sizing, in certain refractive
      surgery techniques, pars-plana sclerotomies, and intravitreal injection sites, or
      in measuring amounts in strabismus to name a few. Errors in calibration of
      ophthalmic calipers must be acknowledged and avoided.

PMID- 22153639
TI  - In vitro comparison of the cytotoxic effects of clinically available ophthalmic
      solutions of fluoroquinolones on human keratocytes.
AB  - OBJECTIVE: To compare the cytotoxic effects of preserved versus unpreserved
      commercially available ophthalmic preparations of fluoroquinolones on human
      keratocytes in vitro. DESIGN: Experimental study. METHODS: Human keratocytes in
      vitro were incubated for 15 or 60 minutes with commercially available
      preparations containing different types of fluoroquinolones, with or without
      benzalkonium chloride. We examined the morphologic aspects of the cultures by an
      inverted-phase contrast microscope and the release of cytoplasmic enzyme lactate
      dehydrogenase into the medium immediately or 24 hours after exposure to drugs.
      RESULTS: Whereas preparations of ofloxacin, norfloxacin, and gatifloxacin, all
      containing benzalkonium chloride, and moxifloxacin, which is preservative-free,
      displayed various degrees of cytotoxicity in our model, the unpreserved monodose
      preparation of norfloxacin was virtually devoid of harmful effects under our
      experimental conditions. CONCLUSIONS: Our in vitro results indicated the
      cytotoxic role of preservatives in commercial preparations of fluoroquinolones
      and the relative nontoxicity of monodose unpreserved norfloxacin, even when
      keratocytes were incubated with this formulation for 6 hours.

PMID- 22153640
TI  - A meta-analysis of primary dacryocystorhinostomy with and without silicone
      intubation.
AB  - OBJECTIVE: To examine possible differences in success rates of primary
      dacryocystorhinostomy (DCR) with and without silicone intubation, and to find out
      whether the use of silicone tubes is beneficial. DESIGN: A literature search was
      conducted in the PubMed, EMBASE, and Cochrane Controlled Trials Register to
      identify potentially relevant controlled trials. METHODS: Language was restricted
      to English. The surgical techniques were categorized into external DCR (EX-DCR),
      endonasal laser-assisted DCR (LA-DCR), and nonlaser endoscopic endonasal DCR
      techniques (EN-DCR). The main outcome measure was success rates after DCR-with
      and DCR-without silicone intubation. The statistical analysis was carried out
      using a RevMan 5.0 software. RESULTS: Of 188 retrieved trials from the electronic
      database, 9 trials (5 randomized controlled trials and 4 cohort studies)
      involving 514 cases met our inclusion criteria. There was no statistically
      significant heterogeneity between the studies. The pooled risk ratio was 0.99,
      with a 95% confidence interval (0.91-1.08). There was no significant difference
      in the success rates between the DCR with and without silicone intubation (p =
      0.81). Sensitivity analysis and subgroups analyses suggested that the result was
      comparatively reliable. CONCLUSIONS: Based on this meta-analysis that included 5
      randomized controlled trials and 4 cohort studies, no benefit was found for
      silicone tube intubation in primary DCR. Further well-organized, prospective,
      randomized studies involving larger patient numbers are required.

PMID- 22153641
TI  - Clopidogrel therapy in ophthalmic procedures: a survey of subspecialty
      ophthalmologists and review of current guidelines.
AB  - OBJECTIVE: To assess the knowledge and practice of subspecialty ophthalmologists
      with respect to perioperative clopidogrel therapy in ophthalmic procedures.
      DESIGN: Mail survey composed of 5 questions. PARTICIPANTS: Fifteen subspecialty
      ophthalmologists (3 in each of the fields of surgical retina, anterior segment,
      oculoplastics, strabismus, and glaucoma) in 3 academic centers in Toronto,
      Ontario. METHODS: Study parcipants completed an anonymous mail survey consisting
      of multiple-choice and short-answer questions. We studied participants' knowledge
      about and clinical practices regarding the use of clopidogrel in the
      perioperative period of specified ophthalmic procedures. We evalutated perceived
      risks of halting clopidogrel indicated for both primary and secondary prevention
      of cardiovascular events, as well as clinical decisions regarding clopidogrel in
      the perioperative period of specified ophthalmic procedures. RESULTS: There was
      marked variability and relative lack of knowledge by subspecialty
      ophthalmologists in the management of clopidogrel in the perioperative period.
      Only 1 respondent identified coronary stent thrombosis or restenosis as a
      potential and life-threatening risk of halting clopidogrel therapy in these
      patients. CONCLUSIONS: In patients with coronary stents, the risks of halting
      clopidogrel therapy in the perioperative period are potentially life-threatening
      and include stent thrombosis and myocardial infarction. Ophthalmic surgeons
      should pay close attention to the indications for clopidogrel therapy in their
      patients and should enlist appropriate collaboration with their colleagues in
      cardiology to minimize risks to their patients.

PMID- 22153642
TI  - Evaluation of investigator bias in industry-funded clinical trials of
      latanoprost.
AB  - OBJECTIVE: To determine whether sponsorship of prostaglandin analogue (PGA)
      clinical trials results in investigator bias in outcomes when studying
      intraocular pressure (IOP). DESIGN: Retrospective, observational cohort study.
      METHODS: A PubMed search was performed for latanoprost or Xalatan, bimatoprost or
      Lumigan, and travoprost or Travatan, with limits to humans, clinical trials, and
      English language. Inclusion criteria included randomized controlled trials, open
      angle glaucoma, monotherapy with a PGA, baseline IOP >= 21 mm Hg, washout period,
      and minimum 1-month follow-up. Each article was reviewed by 2 independent
      reviewers. The results of IOP for each PGA were categorized as being sponsored by
      the parent company (the company manufacturing the PGA); by the competing company
      (the company manufacturing competing glaucoma therapy); or by a nonindustry
      source. The mean IOP and changes in IOP from baseline were compared among the 3
      categories of sponsorship. RESULTS: Only studies involving latanoprost were
      analyzed because of the low number of studies meeting the inclusion criteria for
      bimatoprost and travoprost. We found 29 and 13 studies that provided 1- and 3
      month data, respectively, for analysis. The mean baseline IOPs in the 3 groups
      (parent company, competing company, nonindustry) were not significantly different
      (p = 0.47). The mean IOP at 1 (p = 0.72) and 3 months (p = 0.59) and the change
      in IOP from baseline (p = 0.83 and 0.90, respectively) were not significantly
      different in the 3 groups. A random-effects metaregression controlling for the
      covariates of blinding, naivete to PGAs, and baseline IOP < 24 mm Hg or >= 24 mm
      Hg did not change the findings. CONCLUSION: There was no evidence of investigator
      bias in determining outcomes for IOP in these clinical trials of latanoprost.

PMID- 22153643
TI  - Bleb needling with subconjunctival injection of sodium hyaluronate 1.4%: 1-year
      outcomes.
AB  - OBJECTIVES: To assess the safety and efficacy of 5-fluorouracil (5-FU)-augmented
      bleb needling revision (BNR) with subconjunctival Healon GV (sodium hyaluronate
      1.4%) over a 12-month follow-up. DESIGN: Retrospective consecutive case series.
      PARTICIPANTS: We studied 54 patients who had undergone primary BNR with
      adjunctive 5-FU and routine subconjunctival Healon GV between 2004 and 2007.
      METHODS: BNR was performed using multiple puncturing motions through the bleb: a
      0.4 mL Healon GV injection between the bleb and conjunctiva; and a 5-FU (10 mg in
      0.4 mL) injection into the substance of Healon GV. Success was defined as
      follows: (1) complete success, indicating intraocular pressure (IOP) reduction >=
      20% and to <= 21 mm Hg but > 5 mm Hg without antiglaucoma medication; or (2)
      qualified success, indicating IOP reduction >= 20% and to <= 21 mm Hg but > 5 mm
      Hg with or without antiglaucoma medication. Patients requiring additional
      filtration surgery during the 12-month follow-up period were considered failures.
      RESULTS: Data collection was completed for 53 eyes of 46 patients. The IOP fell
      from a preoperative mean of 22.7 +/- 7.95 mm Hg to 16.3 +/- 4.34 mm Hg at 12
      months (p < 0.001). The complete success rate was 26.4%; the qualified success
      rate was 43.4%. Of the eyes studied, 28 (52.8%) achieved IOPs of <= 16 mm Hg at
      12 months. Complications occurred in 16 eyes (30%), and 3 required surgical
      intervention. CONCLUSIONS: Subconjunctival Healon GV in 5-FU-augmented bleb
      needling revision is a relatively safe and effective technique for reducing IOP
      in the short to medium term, and it involves few significant complications.

PMID- 22153644
TI  - Spectral-domain optical coherence tomography for early glaucoma assessment:
      analysis of macular ganglion cell complex versus peripapillary retinal nerve
      fiber layer.
AB  - OBJECTIVE: We sought to compare the glaucoma discrimination ability of macular
      inner retinal layer (MIRL) thickness with that of conventional peripapillary
      retinal nerve fiber layer (pRNFL) thickness as measured by spectral-domain
      optical coherence tomography (SD-OCT) in patients with early glaucoma. DESIGN:
      Cross-sectional study. PARTICIPANTS: We studied 67 patients with early glaucoma
      (visual field mean deviation index >=-6 dB), and 56 healthy subjects were
      prospectively enrolled. METHODS: All patients underwent MIRL thickness
      measurement (ganglion cell complex [GCC] scan) and pRNFL thickness measurement
      (3.45 mm scan) by SD-OCT. Whenever both eyes were eligible, one was randomly
      selected. Receiver operating characteristic curves and sensitivities at fixed
      specificities were generated for different parameters. The areas under the
      receiver operating characteristic curves (AUCs) of each parameter were compared.
      RESULTS: The average mean deviation for the glaucomatous eyes was -2.5 +/- 1.6
      dB. The AUCs for average (0.815); superior (0.807); and inferior (0.788) MIRL
      thicknesses were not significantly different (p >= 0.18). The AUCs for average
      (0.735); superior (0.728); and inferior (0.697) pRNFL thicknesses were also
      similar (p >= 0.15). Average MIRL thickness had a significantly larger AUC
      compared to average pRNFL thickness analysis (0.815 vs 0.735; p = 0.03).
      Sensitivities at 80% specificity for average MIRL and pRNFL thicknesses were
      66.7% (cutoff, 89.9 MUm) and 62.9% (cutoff, 111.8 MUm), respectively.
      CONCLUSIONS: The GCC scan showed a similar or even a slightly better ability to
      discriminate between healthy and early glaucomatous eyes compared to the pRNFL
      scan. Different from previous analyses considering total macular thickness, the
      GCC macular scan seems to be a useful tool for identification of early structural
      damage in patients with glaucoma.

PMID- 22153645
TI  - RE: Ocular treatment of diabetic macular edema in Canada: where are we going?

PMID- 22153646
TI  - Can genetic factors predict response to antivascular endothelial growth factor
      therapy in age-related macular degeneration?

PMID- 22153647
TI  - Choroidal metastasis from a mediastinal choriocarcinoma in a male.

PMID- 22153648
TI  - Acute orbital inflammatory syndrome following H1N1 immunization.

PMID- 22153649
TI  - Persistent eyelid swelling in a child caused by Cuterebra myiasis.

PMID- 22153650
TI  - Oblique illumination and trypan blue to enhance visualization through corneal
      scars in cataract surgery.

PMID- 22153651
TI  - Endogenous bacterial endophthalmitis after routine colonoscopy.

PMID- 22153653
TI  - Double fertilization on the move.
AB  - Double fertilization is a flowering plant mechanism whereby two immotile sperm
      cells fertilize two different female gametes. One of the two sperm cells
      fertilizes the egg cell to produce the embryo and the other fertilizes the
      central cell to produce the endosperm. Despite the biological and agricultural
      significance of double fertilization, the mechanism remains largely unknown owing
      to difficulties associated with the embedded structure of female gametes in the
      maternal tissue. However, molecular genetic approaches combined with novel live
      cell imaging techniques have begun to clarify the actual behavior of the sperm
      cells, which is different from that described by previous hypotheses. In this
      review article, we discuss the mechanism of double fertilization based on the
      dynamics of the two sperm cells in Arabidopsis.

PMID- 22153652
TI  - Common genetic variants in complement genes other than CFH, CD46 and the CFHRs
      are not associated with aHUS.
AB  - It is well established that common genetic variants in CFH, CD46 and the CFHRs
      are additional risk factors for the development of aHUS. To examine the
      hypothesis that common variants in other complement genes have a similar effect
      we genotyped 501 SNPs in 47 complement genes in 94 aHUS patients from Newcastle,
      126 aHUS patients from Paris, 374 UK controls and 165 French controls. We
      replicated the associations in CFH, CD46 and the CFHRs but found no association
      with any other complement gene. The strongest associations replicated in both
      cohorts were found for four SNPs within CD46 (p-value<10(-3)) and five SNPs
      within CFH (p-value<5*10(-3)). Significant replicable associations with single
      SNPs in CFHR2, CFHR4 and an intergenic SNP (CR1-CD46) were also found. Analysis
      of the Paris cohort showed that the association with CD46 SNPs was only present
      in those patients with complement mutations. Haplotype analysis showed at-risk
      and protective haplotypes in both CD46 and CFH. The CD46 haplotype was only
      disease-associated in those patients with mutations.

PMID- 22153654
TI  - Biomechanical optimisation of the length ratio of the two endosseous portions in
      distraction implants: a three-dimensional finite element analysis.
AB  - Insufficient alveolar height is one of the most common problems in oral
      implantation, and it may preclude placement of an implant or compromise the final
      aesthetic outcome of the restoration. To solve this problem, distraction implants
      (DIs) have been introduced because they can fulfill the functions of bony
      augmentation and implantation simultaneously and facilitate the operation,
      minimise the trauma, and shorten the duration of treatment. However, the high
      risk of complications such as device fracture from uneven distribution of stress
      or transport bone resorption from insufficient blood supply, has impeded their
      clinical use. As the cortical transport portion of the DI is more important for
      bearing occlusal force than the apical support portion, and the length of the
      transport portion is normally the height of the transport bone segment,
      lengthening the transport portion may help to obtain a rational distribution of
      stress and increase the blood supply to the transport bone. For those cases in
      which alveolar height is limited, the dimension of the DI must be minimised to be
      applicable, so it is important to find an optimised balance between the lengths
      of the transport and support portions for a better performance. We have made a
      finite element analysis to optimise the length ratio of transport:support
      portions. The effects of the length ratios on the stress distribution in the
      jawbones were evaluated. A ratio of 8:2 showed the minimum stress and most
      resistance to displacement. These results provide a valuable reference for
      further improvement of designs of DI and help to promote its clinical
      application.

PMID- 22153655
TI  - Current status of residency training of allergic-like adverse events to contrast
      media.
AB  - RATIONALE AND OBJECTIVES: Acute allergic-like adverse reactions to contrast media
      are rare but life-threatening events. Residents may complete training without
      ever managing such an event. Surveys have shown practicing radiologists to
      incorrectly dose and administer medications for treatment. Thus, contrast
      education may be deficient or inconsistent. The purpose of this study was to
      assess the current status of contrast reaction education in US radiology
      residency programs and the methods used to test residents' knowledge. MATERIALS
      AND METHODS: A 10-question anonymous survey on residency education methods and
      testing pertaining to allergic-like adverse events to contrast media was
      distributed through the Association of Program Directors in Radiology to program
      directors of US diagnostic radiology residency programs. The past 4 years of the
      American College of Radiology in-service examination were reviewed to assess the
      number of contrast reaction questions. RESULTS: Fifty-one programs responded to
      the Association of Program Directors in Radiology survey. Forty-nine percent of
      programs train with one lecture per year, 29.4% train with two lectures, and 16%
      train with three or more lectures. Only 44% include role-playing training during
      the lectures. Eighteen percent of programs are incorporating simulation training.
      Fewer than 50% of programs formally test residents' knowledge, and there were no
      questions on the 2007 to 2010 American College of Radiology in-service
      examinations. CONCLUSIONS: Resident education for contrast reaction management is
      primarily performed with annual lectures. Only 18% of programs are using
      simulation training, and <50% are testing residents' knowledge or skills. These
      findings suggest that education may need revision to incorporate simulation or
      other means of psychomotor learning.

PMID- 22153656
TI  - Value of magnetic resonance imaging for nodal staging in patients with head and
      neck squamous cell carcinoma: a meta-analysis.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of magnetic resonance imaging
      (MRI) in detecting lymph node metastases in patients with head and neck squamous
      cell carcinoma (HNSCC). METHODS: MEDLINE, EMBASE, the CBM disc databases, and
      other databases were searched for relevant original articles published between
      January 1990 and January 2011. Meta-analysis methods were used to pool
      sensitivity and specificity and to construct summary receiver-operating
      characteristic, and to calculate positive and negative likelihood ratios (LR+ and
      LR-). We also compared the performance of MRI with other diagnostic methods
      (positron emission tomography, computed tomography, and ultrasound) by analyzing
      studies that had also used these diagnostic methods on the same patients.
      RESULTS: Across 16 studies, there was no evidence of publication bias (P = .15).
      Sensitivity and specificity of MRI for cervical lymph node status in patients
      with HNSCC across all studies were 76% (95% CI: 70%-82%) and 86% (95% CI: 73%
      93%), respectively. Overall, Positive likelihood ratios was 5.47 (95% CI: 2.69
      11.11) and positive negative likelihood ratios was 0.28 (95% CI: 0.21-0.36),
      respectively. The comparison of MRI performance with that of other diagnostic
      tools (positron emission tomography, computed tomography, and ultrasound)
      suggested no major differences against any of these methods. The Subgroup by
      using diffusion-weighted imaging had higher pooled sensitivity (0.86, 95% CI 0.78
      0.92) than the subgroup without diffusion-weighted imaging. CONCLUSION: MRI has
      good diagnostic performance in the overall pretreatment evaluation of node
      staging with HNSCC. A limited number of small studies suggest DWI is superior to
      conventional imaging for nodal staging of HNSCC.

PMID- 22153657
TI  - Irreducible tibial pilon fracture caused by incarceration of the fibula in the
      tibial medullary canal.
AB  - Fractures can be irreducible for several reasons, including soft tissue or bone
      fragment interposition. We report an unusual fracture configuration of a
      comminuted tibial pilon fracture in which the distal fibular shaft fragment was
      occupying the medullary canal of the proximal tibial shaft fragment and
      inhibiting reduction and fixation. To the best of our knowledge, this has not
      been previously reported in a published study.

PMID- 22153658
TI  - Complete open dislocation of the navicular: a case report.
AB  - Complete dislocation of the navicular is rare, and open dislocation even more so.
      We report a case of a 85-year-old female patient who experienced complete open
      dislocation of navicular, successfully treated by open reduction and arthrodesis
      of the naviculocuneiform and calcaneocuboid joints. At 2 years after treatment,
      the patient was symptom free and had nearly normal foot function.

PMID- 22153659
TI  - Nonunion rate of first metatarsal-phalangeal joint arthrodesis with crossed
      titanium flexible intramedullary nails and a dorsal static staple with immediate
      weightbearing.
AB  - Myriad forms of fixation have been proposed for arthrodesis of the first
      metatarsal-phalangeal joint (MTPJ). Regardless of fixation type, nonunion of the
      arthrodesis site has been purported as a common complication. We performed a
      retrospective review of all patients undergoing arthrodesis of the first MTPJ
      with crossed flexible titanium intramedullary nails and a dorsal static staple
      followed by immediate protected weight bearing. The subjects were included if
      they had undergone the exact internal fixation technique described; surgery had
      been performed only by 1 of us; and they had not undergone bilateral surgery in
      the same setting. Also, the indication for surgery was required to be pathology
      of the first MTPJ other than rheumatoid arthritis. Weight bearing preoperative
      radiographs and weight bearing radiographs at least 6 weeks postoperatively were
      required. Also, the patients had to have initiated weight bearing on the
      operative foot immediately postoperatively in a protective shoe. Finally,
      documentation of any complications was required. A total of 83 patients (95 feet)
      met the inclusion criteria and were included. Of the 83 patients, 77 (92.7%) were
      female and 6 (7.3%) were male. Their mean age +/- standard deviation was 69.7 +/-
      16.7 years. Of the 95 feet, 55 (57.9%) were right and 40 (42.1%) were left feet.
      The indications included 61 (64.2%) with severe hallux valgus deformity, 24
      (25.3%) with hallux rigidus, and 10 (9.5%) with failed first MTPJ surgery.
      Complications related to technical error during insertion of the crossed titanium
      flexible intramedullary nails occurred in 16 feet (16.8%) but none led to
      nonunion or revision surgery. A total of 3 asymptomatic nonunions (3.2%)
      occurred, all in female patients with severe hallux valgus that did not require
      revision surgery. The incidence of nonunion after arthrodesis of the first MTPJ
      consisting of crossed flexible titanium intramedullary nails and a dorsal static
      staple for predominantly severe hallux valgus and hallux rigidus was lower than
      the historic mean for most other fixation techniques. However, methodologically
      sound prospective cohort studies are still needed that focus on the use of
      isolated arthrodesis of the first MTPJ for purely severe hallux valgus or hallux
      rigidus and a comparison of the technique we have presented with other modern
      osteosynthesis techniques.

PMID- 22153660
TI  - Results of accelerated postoperative rehabilitation using novel "suture frame"
      repair of Achilles tendon rupture.
AB  - The management of Achilles tendon rupture is a much-debated subject. In recent
      years, there has been much interest in early postoperative mobilization. We
      present the results of our Achilles tendon repair technique and accelerated
      rehabilitation program. The technique we propose uses the strength of a 1-loop
      polydioxanone "suture frame" to enable restoration of the tendon length,
      immediate positioning of the foot in a near-plantigrade position, and an
      accelerated rehabilitation program. We followed up 15 cases of Achilles tendon
      rupture treated with this technique. The initial follow-up was a review of case
      notes and a telephone questionnaire. All patients were subsequently invited for a
      clinical follow-up visit, and 11 patients (68.75%) attended. No cases of
      infection or repeat rupture occurred. The return to work (mean 5.6 weeks) and
      return to sport (mean 4.8 months) were relatively rapid. Regarding overall
      satisfaction on a scale of 0 to 10, the median was 9 (range 8 to 10). Of the 11
      patients who attended the clinical follow-up visit, the mean American Orthopaedic
      Foot and Ankle Surgery ankle-hindfoot score was 94.5 points (range 83 to 100).
      The Achilles rupture repair scores (including isokinetic muscle strength) were
      good or excellent in all but 1 patient, whose result was fair. Of the 11
      patients, 10 reported complete satisfaction with their outcome. Our technique
      with accelerated rehabilitation is safe and effective in the management of acute
      Achilles tendon rupture. It facilitates an early return to work and recreational
      sports, with excellent overall patient satisfaction.

PMID- 22153661
TI  - Subjective results after surgical treatment for displaced intra-articular
      calcaneal fractures.
AB  - We present a retrospective study investigating the results of the subjective
      assessment of displaced intra-articular calcaneal fractures in a selected cohort
      of 42 patients treated operatively, with a follow-up duration of at least 3
      years. The adjusted American Orthopaedic Foot and Ankle Society questionnaire,
      Foot Function Index, and visual analog scale were used to quantify the subjective
      evaluations. Our hypothesis was that good subjective results could be predicted
      and obtained in patients with specific characteristics if anatomic reduction of
      the fracture was achieved. The results of the study confirmed our hypothesis. A
      number of specific subgroup analyses were undertaken. The study confirmed that
      Bohler angle restoration and the quality of reduction of the subtalar joint facet
      are important prognostic factors related to the outcome. In contrast, gender and
      Sanders type had less influence at the intermediate-term follow-up results. The
      main weaknesses of the present study included its retrospective nature, the lack
      of a control group managed nonoperatively for comparison, and the small sample
      size. Moreover, the operating surgeon performed the radiographic measurement and
      categorized the quality of the surgical reconstruction.

PMID- 22153662
TI  - Discovery of AZD2932, a new Quinazoline Ether Inhibitor with high affinity for
      VEGFR-2 and PDGFR tyrosine kinases.
AB  - A new series of Quinazoline Ether Inhibitor which potently inhibits VEGFR-2 and
      PDGFR tyrosine kinases is described here. In vitro, pharmacokinetics and in vivo
      evaluations led to the selection of AZD2932.

PMID- 22153663
TI  - Ligand based design of novel histamine H4 receptor antagonists; fragment
      optimization and analysis of binding kinetics.
AB  - The histamine H(4) receptor is a G protein-coupled receptor that has attracted
      much interest for its role in inflammatory and immunomodulatory functions. In our
      search for new H(4)R ligands, a low affinity isoquinoline fragment was optimized
      to 7-(furan-2-yl)-4-(piperazin-1-yl)quinazolin-2-amine (VUF11489), as a new H(4)R
      antagonist. Analysis of its binding kinetics at the human H(4)R showed this
      compound to have a very different dissociative half-life in comparison with
      reference antagonist JNJ7777120.

PMID- 22153664
TI  - Significance of complement components C1q and C4 bound to circulating immune
      complexes in juvenile idiopathic arthritis: support for classical complement
      pathway activation.
AB  - OBJECTIVES: Immune complexes (ICs) from sera of juvenile idiopathic arthritis
      (JIA) patients show increased complement opsonisation; however, a definitive role
      for involvement of the classical or alternative pathway is not entirely clear. To
      delineate the role of these pathways, we measured activated complement products
      bound to circulating IC (CICs) in the sera of JIA patients. METHODS: Sera from
      100 JIA patients and 22 healthy children were collected. C1q, C4, C3, C3d, and
      membrane attack complex (MAC) bound to CICs were measured by enzyme-linked
      immunosorbent assay. Data was compared to IgM rheumatoid factor (RF), IgG anti
      cyclic citrullinated peptide (CCP) antibodies, C-reactive protein (CRP), and
      erythrocyte sedimentation rate (ESR) levels. RESULTS: Mean levels of C1q, C4, and
      MAC bound to CICs were significantly elevated in JIA patients compared to healthy
      children. C1q correlated significantly with C4 and MAC bound to CICs and C4 and
      MAC also demonstrated significant correlation. No significant differences were
      noted in complement components bound to CICs when evaluating IgM RF, anti-CCP
      antibody, and CRP positivity. A significant correlation was noted between MAC
      bound to CICs and ESR. C1q and MAC bound to CICs mean levels were significantly
      higher in patients with an elevated ESR compared to those with a normal ESR
      level. CONCLUSIONS: JIA patients have elevated levels of complement components
      bound to CICs, particularly from the classical pathway. Moreover, classical
      pathway components were associated with ESR, a marker of disease activity. MAC
      bound to CICs also correlated significantly with ESR, further supporting the
      notion of complement-mediated tissue injury that is triggered by IC-mediated
      classical pathway activation.

PMID- 22153665
TI  - The effect of a long-distance run on plantar pressure distribution during
      running.
AB  - The purpose of this study was to assess plantar pressure alterations after long
      distance running. Prior to and after a 20 km run, force distribution underneath
      the feet of 52 participants was registered using Footscan((r)) pressure plates
      while the participants ran shod at a constant self-selected pace. Peak force,
      mean force and impulse were registered underneath different zones of the foot. In
      addition, temporal data as total foot contact time, time of contact and end of
      contact were derived for these zones. Furthermore, a medio-lateral pressure
      distribution ratio was calculated in different phases of the roll-off. After the
      run, increases in the loading of the forefoot, midfoot and medial heel were noted
      and decreases in loading of the lateral toes. In the forefoot push off phase a
      more lateral pressure distribution was observed. The results of this study
      demonstrated plantar pressure deviations after long-distance running which could
      give additional information related to several running injuries.

PMID- 22153666
TI  - Age-related differences in kinetic measures of landing phase lateral stability
      during a balance-restoring forward step.
AB  - Lateral stability during stepping is critical to successful balance recovery, and
      has been previously studied from a kinematics perspective. However, relatively
      little is known about the kinetic aspects of lateral stability. The purpose of
      this paper is to investigate age-related changes in laterally directed landing
      phase ground and joint reactions during a balance-restoring step response. 12
      young and 13 older male adults were released from a static forward leaning
      position and were instructed to take a single step with the dominant leg.
      Laterally directed landing phase ground and ankle reactions, foot kinematics, and
      center of mass movement were compared across age groups. No age-related
      differences were observed in step width or center of mass behavior during step
      landing. Older adults, compared to young, demonstrated larger laterally directed
      landing phase ground and ankle reaction forces. The findings demonstrate an age
      related increase in kinetic, but not kinematic or stability measures, suggesting
      that older adults do not minimize strength when maintaining stability during a
      single step balance recovery maneuver.

PMID- 22153668
TI  - Male osteoporosis and glucocorticoid-induced osteoporosis 2nd National ODISSEE
      Meetings (Osteoporosis: DIagnosis and Surveillance of SEvErity). Foreword.

PMID- 22153667
TI  - Motor cortical functional geometry in cerebral palsy and its relationship to
      disability.
AB  - OBJECTIVE: To investigate motor cortical map patterns in children with diplegic
      and hemiplegic cerebral palsy (CP), and the relationships between motor cortical
      geometry and motor function in CP. METHODS: Transcranial magnetic stimulation
      (TMS) was used to map motor cortical representations of the first dorsal
      interosseus (FDI) and tibialis anterior (TA) muscles in 13 children with CP (age
      9-16 years, 6 males.) The Gross Motor Function Measure (GMFM) and Melbourne upper
      extremity function were used to quantify motor ability. RESULTS: In the
      hemiplegic participants (N = 7), the affected (right) FDI cortical representation
      was mapped on the ipsilateral (N = 4), contralateral (N = 2), or bilateral (N =
      1) cortex. Participants with diplegia (N = 6) showed either bilateral (N = 2) or
      contralateral (N = 4) cortical hand maps. The FDI and TA motor map center-of
      gravity mediolateral location ranged from 2-8 cm and 3-6 cm from the midline,
      respectively. Among diplegics, more lateral FDI representation locations were
      associated with lower Melbourne scores, i.e. worse hand motor function
      (Spearman's rho = -0.841, p = 0.036). CONCLUSIONS: Abnormalities in TMS-derived
      motor maps cut across the clinical classifications of hemiplegic and diplegic CP.
      The lateralization of the upper and lower extremity motor representation
      demonstrates reorganization after insults to the affected hemispheres of both
      diplegic and hemiplegic children. SIGNIFICANCE: The current study is a step
      towards defining the relationship between changes in motor maps and functional
      impairments in CP. These results suggest the need for further work to develop
      improved classification schemes that integrate clinical, radiologic, and
      neurophysiologic measures in CP.

PMID- 22153669
TI  - Male osteoporosis: do sex steroids really benefit bone health in men?

PMID- 22153670
TI  - Why and how should we investigate men for osteoporosis?

PMID- 22153671
TI  - Male osteoporosis: who should be treated and how?

PMID- 22153672
TI  - Management of male osteoporosis: lessons for clinical practice.

PMID- 22153673
TI  - Are glucocorticoids really deleterious to bone health?

PMID- 22153674
TI  - Glucocorticoid-induced osteoporosis: when and who should we treat?

PMID- 22153675
TI  - Selecting the optimal treatment for glucocorticoid-induced osteoporosis.

PMID- 22153676
TI  - Management of glucocorticoid-induced osteoporosis: lessons for clinical practice.

PMID- 22153677
TI  - Placenta-imprinted gene expression association of infant neurobehavior.
AB  - OBJECTIVE: To identify links between altered gene imprinting in the placenta and
      infant neurobehavioral profiles. STUDY DESIGN: Quantitative reverse-transcription
      polymerase chain reaction was used to examine the expression of 22 imprinted
      candidate genes in a series of 106 term human primary placenta tissues. The
      expression pattern uncovered was associated with Neonatal Intensive Care Unit
      Network Neurobehavioral Scales summary scores in the corresponding infants.
      Clustering of the expression data was used to define distinct classes of
      expression. RESULTS: Significant associations were identified between classes of
      expression and the Neonatal Intensive Care Unit Network Neurobehavioral Scales
      quality of movement (P = .02) and handling (P = .006) scores. Multivariate
      regression demonstrated an independent effect of imprinted gene expression
      profile on these neurobehavioral scores after controlling for confounders.
      CONCLUSION: These results suggest that alterations in imprinted gene expression
      in the placenta are associated with infant neurodevelopmental outcomes, and
      suggest a role for the placenta and genomic imprinting in the placenta beyond
      intrauterine growth regulation.

PMID- 22153678
TI  - Post-term birth is associated with greater risk of obesity in adolescent males.
AB  - OBJECTIVE: To test the hypothesise that post-term birth (>42 weeks gestation)
      adversely affects longitudinal growth and weight gain throughout childhood. STUDY
      DESIGN: A total of 525 children (including 17 boys and 20 girls born post-term)
      were followed from birth to age 16 years. Weight and height were recorded
      prospectively throughout childhood, and respective velocities from birth to end
      of puberty were calculated using a mathematical model. RESULTS: At birth, post
      term girls were slimmer than term girls (ponderal index, 27.7 +/- 2.6 kg/m(3) vs
      26.3 +/- 2.8 kg/m(3); P<.05). At age 16 years, post-term boys were 11.8 kg
      heavier than term subjects (body mass index [BMI], 25.4 +/- 5.5 kg/m(2) vs 21.7
      +/- 3.1 kg/m(2); P<.01). The rate of obesity was 29% in post-term boys and 7% in
      term boys (P<.01), and the combined rate of overweight and obesity was 47% in
      post-term boys and 13% in term boys (P<.01). Weight velocity, but not height
      velocity, was higher in post-term boys at age 1.5-7 years (P<.05) and again at
      age 11.5-16 years (P<.05). BMI was higher in post-term boys at age 3 years, with
      the difference increasing thereafter. BMI and growth were similar in post-term
      and term girls. CONCLUSION: In this post-term birth cohort, boys, but not girls,
      demonstrated accelerated weight gain during childhood, leading to greater risk of
      obesity in adolescence.

PMID- 22153680
TI  - Peripheral nerve blockade under general anesthesia--benefits not shown to
      outweigh risk.

PMID- 22153679
TI  - Prevalence of persistent prehypertension in adolescents.
AB  - OBJECTIVE: To measure the prevalence of persistent prehypertension in
      adolescents. STUDY DESIGN: We collected demographic and anthropometric data and 4
      oscillometric blood pressure (BP) measurements on 1020 students. The mean of the
      second, third, and fourth BP measurements determined each student's BP status per
      visit, with up to 3 total visits. Final BP status was classified as normal (BP
      <90th percentile and 120/80 mm Hg at the first visit), variable (BP >= 90th
      percentile or 120/80 mm Hg at the first visit and subsequently normal), abnormal
      (BP >= 90th percentile or 120/80 mm Hg at 3 visits but not hypertensive), or
      hypertensive (BP >= 95th percentile at 3 visits). The abnormal group included
      those with persistent prehypertension (BP >= 90th percentile or 120/80 mm Hg and
      <95th percentile on 3 visits). Statistical analysis allowed for comparison of
      groups and identification of characteristics associated with final BP
      classification. RESULTS: Of 1010 students analyzed, 71.1% were classified as
      normal, 15.0% as variable, 11.5% as abnormal, and 2.5% as hypertensive. The
      prevalence of persistent prehypertension was 4.0%. Obesity similarly affected the
      odds for variable BP (OR, 3.9; 95% CI, 2.5-6.0) and abnormal BP (OR, 3.4; 95% CI,
      2.0-5.9), and dramatically increased the odds for hypertension (OR, 38.4; 95% CI,
      9.4-156.6). CONCLUSION: Almost 30% of the students had at least one elevated BP
      measurement significantly influenced by obesity. Treating obesity may be
      essential to preventing prehypertension and/or hypertension.

PMID- 22153682
TI  - Review: Parent-offspring conflict and the control of placental function.
AB  - Evolutionary genetic arguments suggest that pregnancy is not a fully cooperative
      engagement between the mother and embryo. Trivers' concept of parent-offspring
      conflict indicates that the mother and embryo will disagree over the level of
      maternal investment in the pregnancy. Therefore, selection will favour mechanisms
      encoded by maternal genes that limit resource transfer to the embryo and
      mechanisms encoded by embryonic genes that enhance such transfer. These
      antagonistic selection pressures may have influenced the evolution of many
      aspects of placental regulation and function, including genomic imprinting and
      placental hormone production. However, the mother and embryo are not expected to
      disagree over aspects of placental function that benefit both parties; for
      example, regulation of haemostasis or resistance to infections etc. Therefore, an
      understanding of the complex regulation of placental function must consider the
      multiple selection pressures acting on this organ.

PMID- 22153683
TI  - Effects of iron deficiency anemia and its treatment with iron polymaltose complex
      in pregnant rats, their fetuses and placentas: oxidative stress markers and
      pregnancy outcome.
AB  - OBJECTIVE: Iron deficiency anemia (IDA) can severely impair the outcome of
      pregnancy. IDA has been shown to cause oxidative stress, which may be exacerbated
      by oral iron therapy. In this study, the effects of IDA and its treatment with
      iron polymaltose complex/folic acid (IPC/FA) were examined in anemic pregnant
      rats, their fetuses and placentas. STUDY DESIGN: Hematological variables and
      oxidative stress markers in the liver, heart and kidney were evaluated in non
      anemic, anemic and IPC/FA-treated pregnant rats and their fetuses. Markers for
      oxidative stress, inflammation and hypoxia were assessed in the placentas of all
      groups. RESULTS: IDA was shown to increase oxidative stress levels in all the
      studied organs and in placenta as well as hypoxia and inflammation in placenta.
      IPC/FA treatment corrected IDA measured by the hemoglobin level, serum iron level
      and transferrin saturation. The oxidative stress levels in all the studied organs
      and in placentas of the IPC/FA-treated group were comparable to those of the non
      anemic group. The number of fetuses and the neonatal and placental weight were
      lower in the anemic group compared to the non-anemic and IPC/FA-treated groups.
      CONCLUSIONS: The current study shows that IDA in pregnant rats impaired pregnancy
      outcome, increased the expression of hypoxia and inflammatory markers in the
      placenta, and increased oxidative stress in dams, fetuses and placentas.
      Treatment with oral IPC/FA corrected the IDA as well as reduced the levels of
      oxidative stress and inflammatory markers close to non-anemic control values in
      all the studied organs.

PMID- 22153684
TI  - Fibrinogen replacement therapy: a critical review of the literature.

PMID- 22153685
TI  - Trends in cord blood banking.
AB  - BACKGROUND: Umbilical cord blood (UCB) is a source of hematopoietic precursor
      cells for transplantation. The creation of UCB banks in 1992 led to the
      possibility of storing units of UCB for unrelated transplants. The distribution
      of cell contents in historical inventories is not homogenous and many units are
      not, therefore, suitable for adults. The aim of this study was to analyse our UCB
      bank inventory, evaluate the units released for transplantation and calculate the
      cost of the current process per unit of UCB stored. METHODS: Three study periods
      were defined. In the first period, from January 1996 to January 2006, the total
      nucleated cell (TNC) count acceptable for processing was 4-6*10(8) and a manual
      processing system was used. In the second period, from October 2006 to July 2010,
      processing was automated and the acceptable TNC count varied from 8-10*10(8). In
      the third period, from January 2009 to June 2010, an automated Sepax-BioArchive
      procedure was used and the accepted initial TNC count was >10*10(8). Within each
      period the units were categorised according to various ranges of cryopreserved
      TNC counts in the units: A, >16.2*10(8); B1, from 12.5-16.1*10(8); B2, from 5.2
      12.4*10(8); and C, <5.1*10(8). RESULTS: The third period is best representative
      of current practices, with homogenous TNC acceptance criteria and automated
      processing. In this period 15.7% of the units were category A and 25.5% were
      category B. Overall, the mean TNC count of units released for transplantation was
      14*10(8) (range, 4.6*10(8) to 36.5*10(8)). The cost of the processed UCB in 2009
      was 720.41 euros per unit. CONCLUSION: An UCB bank should store units of high
      quality, in terms of the TNC count of units issued for transplantation, have a
      training programme to optimise the selection of donors prior to delivery, use
      similar volume reduction systems and homogenous recovery indices, express its
      indicators in the same units, use validated analytical techniques, and bear in
      mind ethnic minorities.

PMID- 22153686
TI  - Low frequency of occult hepatitis B infection in anti-HBc seropositive blood
      donors: experience from a tertiary care centre in South India.

PMID- 22153687
TI  - Clinical significance of serum cytokine levels and thrombopoietic markers in
      childhood idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: Biological markers useful for defining children with newly diagnosed
      immune thrombocytopenic purpura (ITP) who are likely to develop the chronic form
      of the disease are partially lacking. The purpose of this study was to assess the
      clinical role of both immunological and thrombopoietic markers in children with
      ITP and correlate their levels with different disease stages. MATERIALS AND
      METHODS: We enrolled 28 children with ITP at the onset of their disease, who were
      followed-up for a whole year and divided according to whether their disease
      resolved within the 12 months (n=13) or became chronic (n=15), 11 subjects with
      chronic ITP off therapy for at least 1 month at the time of enrolment, and 30
      healthy matched controls. Serum levels of T helper type 1 and 2 and T regulatory
      associated cytokines, such as interferon gamma, tumour necrosis factor alpha,
      interleukin (IL) 2, IL6, IL10, and thrombopoietin were measured in all children
      using quantitative immunoenzymatic assays, while reticulated platelets were
      evaluated by flow cytometric analysis. RESULTS: Serum IL10 levels were
      significantly higher in patients with an acute evolution of ITP than in either
      healthy controls (p<0.001) or patients with chronic progression of ITP (p<0.05).
      Reticulated platelet count and thrombopoietin levels were significantly higher in
      ITP patients at the onset of their disease, whether with acute resolution or
      chronic progression, than in healthy subjects (p<0.01; p<0.001), but did not
      differ between the groups of patients. CONCLUSION: IL-10 seems to predict the
      clinical course of ITP, as it is significantly higher at the onset of disease in
      patients who obtain disease remission in less than 1 year.

PMID- 22153688
TI  - Effects of helicopter transport on red blood cell components.
AB  - BACKGROUND: There are no reported studies on whether a helicopter flight affects
      the quality and shelf-life of red blood cells stored in mannitol-adenine
      phosphate. MATERIALS AND METHODS: Seven days after donation, five aliquots of red
      blood cells from five donors were packed into an SS-BOX-110 container which can
      maintain the temperature inside the container between 2  degrees C and 6  degrees
      C with two frozen coolants. The temperature of an included dummy blood bag was
      monitored. After the box had been transported in a helicopter for 4 hours, the
      red blood cells were stored again and their quality evaluated at day 7 (just
      after the flight), 14, 21 and 42 after donation. Red blood cell quality was
      evaluated by measuring adenosine triphosphate, 2,3-diphosphoglycerate, and
      supernatant potassium, as well as haematocrit, intracellular pH, glucose,
      supernatant haemoglobin, and haemolysis rate at the various time points. RESULTS:
      During the experiment the recorded temperature remained between 2 and 6  degrees
      C. All data from the red blood cells that had undergone helicopter transportation
      were the same as those from a control group of red blood cell samples 7 (just
      after the flight), 14, 21, and 42 days after the donation. Only supernatant Hb
      and haemolysis rate 42 days after the donation were slightly increased in the
      helicopter-transported group of red blood cell samples. All other parameters at
      42 days after donation were the same in the two groups of red blood cells.
      DISCUSSION: These results suggest that red blood cells stored in mannitol-adenine
      phosphate are not significantly affected by helicopter transportation. The
      differences in haemolysis by the end of storage were small and probably not of
      clinical significance.

PMID- 22153689
TI  - Levels of factor VIII and factor IX in fresh-frozen plasma produced from whole
      blood stored at 4  degrees C overnight in Turkey.
AB  - BACKGROUND: The aim of this study was to assess whether the quantities of factor
      VIII and factor IX in fresh-frozen plasma produced from whole blood stored at 4 
      degrees C for 24 hours are adequate for their intended purpose. MATERIALS AND
      METHODS: Fresh-frozen plasma separated from whole blood after storage at 4 
      degrees C overnight (24 hours from donation) was compared with plasma prepared 8
      hours after donation using a standard method. The amounts of factor VIII and
      factor IX obtained with the two methods were compared. RESULTS: Compared to the
      levels of factor VIII and factor IX in plasma prepared within 8 hours of blood
      collection, the levels in plasma prepared after 24 hours of storage at 4  degrees
      C were 25% and 9% lower, respectively. Ninety percent of the factor VIII and 100%
      of the factor IX levels were above 0.5 IU/mL (standard haematology reference
      range) after 24 hours of storage. DISCUSSION: These data suggest that there is
      good retention of coagulation factor activity in plasma produced from whole blood
      stored at 4 oC for 24 hours and that such plasma would be an acceptable product
      for most patients requiring fresh-frozen plasma.

PMID- 22153690
TI  - Evaluation of haemoglobin, haematocrit, haemolysis, residual protein content and
      leucocytes in 345 red blood cell concentrates used for the treatment of patients
      with beta-thalassaemia.
AB  - BACKGROUND: The aim of this study was to evaluate the quality of red blood cell
      concentrates obtained from donated whole blood, selected for transfusion therapy
      of thalassaemic patients, by measuring the following parameters: haemoglobin,
      haematocrit, percentage haemolysis, residual leucocyte count and residual protein
      content. MATERIALS AND METHODS: Overall 345 red cell concentrates were evaluated,
      of which 205 had been filtered in-line pre-storage and washed and 140 were buffy
      coat-depleted and used within 2 days of collection. Of the buffy coat-depleted
      concentrates, 62 were leucodepleted and 78 washed and leucodepleted post-storage
      all within 2 days of collection. The off-line filters used for the leucodepletion
      were gamma-irradiated polyester with a pore size of 200 MUm. The washing
      procedure was automated (Haemonetics ACP 215, Braintree, MA, USA). The
      haematological parameters were evaluated by a blood cell counter (Coulter,
      Ramsey, IL, USA) and the white blood cell count by cytofluorimetry (FACScan).
      RESULTS: Ninety-five percent (194/205) of the red cell concentrates that had been
      filtered pre-storage and washed, 92% (57/62) of the red cell concentrates that
      had been leucodepleted post-storage and 94% (73/78) of the those subjected to
      both treatments had normal values of haemoglobin (>40 g/unit), haematocrit
      (between 50-70%), percentage haemolysis (<0.8/unit), white cell count (<1*10(6))
      and residual protein content (<0.5 g/L). Five percent (11/205) of the red cell
      concentrates that had been filtered pre-storage and washed, 8% (5/62) of those
      leucodepleted post-storage after 2 days and 6% (5/78) of those that underwent
      both procedures had a haemoglobin content <40 g/unit and a haematocrit <50%.
      CONCLUSIONS: The preparation procedures had been carried out satisfactorily;
      nevertheless, transfusion therapy with some "low dose" normal units could be less
      effective and might, therefore, result in greater transfusion requirements in
      patients receiving such units.

PMID- 22153691
TI  - Implementing non-invasive RHD genotyping on cell-free foetal DNA from maternal
      plasma: the Pavia experience.
AB  - BACKGROUND: The occurrence of cell-free foetal DNA in maternal circulation opens
      new possibilities in non-invasive antenatal diagnosis. Real-time polymerase chain
      reaction (PCR) analysis is an useful approach to foetal RhD blood group
      determination, thus being important in the prevention of haemolytic disease of
      foetus and new-born (HDFN). STUDY DESIGN AND METHODS: Using real-time PCR assays
      we typed 20 samples of plasma, provided in a blinded fashion, from the
      International Reference Laboratory, two plasma samples sent by the "2010 Workshop
      on Molecular Blood Group Genotyping"; seven samples from D-negative mothers at
      the 16th week of gestation provided by our Hospital as prospective validation
      cases, and two plasma samples received from the "1(st) Collaborative study
      establishing the sensitivity standard for non-invasive prenatal determination of
      foetal RHD genotype". To confirm the RHD typing of the seven prospective samples,
      PCR with sequence specific primers (PCR-SSP) was applied on genomic DNA from
      amniocytes (5 cases) and paternal peripheral blood (2 cases). RESULTS: The
      results for the 31 investigated samples showed 100% concordance. Our measurable
      benefits were: confidence with a new technology, awareness of having gained the
      European standard level and increased self-assurance regarding the introduction
      of this typing technique in prenatal diagnostics. DISCUSSION: These results
      demonstrate the feasibility and accuracy of our validation protocol. RHD typing
      on cell-free foetal DNA is a procedure which requires particular care and a great
      degree of expertise for diagnostic use. International collaborations are
      essential for monitoring the performance of laboratories in the absence of
      specific quality control programmes.

PMID- 22153692
TI  - Genomic characterisation of the Jk(a-b-) phenotype in Thai blood donors.
AB  - BACKGROUND: The Kidd (JK) blood group antigens are encoded by the JK gene. The
      rare Jk(a-b-) phenotype can be caused by homozygosity for a silent JK allele.
      Currently, JK(null) alleles have been identified among different populations;
      however, information on its presence among Thais is not available. MATERIALS AND
      METHODS: Screening for the Jk(a-b-) phenotype by the urea lysis test was
      performed in 25,340 blood samples from Thai blood donors. The Jk(a-b-) phenotypes
      were confirmed by an indirect antiglobulin test (IAT). Additionally, polymerase
      chain reaction amplification and sequence analysis of the JK gene were performed
      using previously described methods. RESULTS: Five samples were confirmed as
      having a Jk(a-b-) phenotype by a urea lysis test and IAT; four of these samples
      were investigated. Two samples of JK*02 alleles were homozygous for a g>a
      mutation at the 3' acceptor splice site of intron 5 of the JK gene, as in
      previous studies in Asians and Polynesians. Moreover, one sample of JK*02 alleles
      was homozygous for an 896G>A mutation at exon 9 (Gly299Glu), as in a previous
      study in Polynesians. Interestingly, missense dual mutations of JK*01 alleles
      from a female blood donor were identified. The first mutation was 956C>T
      (Thr319Met) in exon 10, as in a recent study in African-Americans. The second
      mutation was 130G>A (Glu44Lys) at exon 4, as in previous studies among
      Caucasians. CONCLUSION: There are various different molecular bases of the Jk(a-b
      ) phenotype. This is the first report of JK(null) alleles among Thais. The
      information presented in this study could be beneficial in planning genotyping
      strategies for blood donors and patients.

PMID- 22153693
TI  - Non-invasive foetal RHD genotyping in transfusion medicine.

PMID- 22153695
TI  - Editor in Chief's Report for Atherosclerosis for 2011.

PMID- 22153694
TI  - On the role of iron therapy for reducing allogeneic blood transfusion in
      orthopaedic surgery.

PMID- 22153696
TI  - Significant differential effects of omega-3 fatty acids and fenofibrate in
      patients with hypertriglyceridemia.
AB  - BACKGROUND: Omega-3 fatty acids and fenofibrate are both used to treat patients
      with hypertriglyceridemia. However, a head-to-head comparison of the lipoprotein
      and metabolic effects of these two medicines has not been published. METHODS:
      This was a randomized, single-blind, placebo-controlled, parallel study. Age,
      sex, and body mass index were matched among groups. All patients were recommended
      to maintain a low fat diet. Fifty patients in each group were given placebo,
      omega-3 fatty acids 2 g (most commonly used dosage in Korean patients), or
      fenofibrate 160 mg, respectively daily for 2 months. RESULTS: Omega-3 fatty acids
      therapy decreased triglycerides by 21% and triglycerides/HDL cholesterol and
      improved flow-mediated dilation (P<0.01), however, did not significantly change
      insulin, plasma adiponectin levels, and insulin sensitivity (determined by
      QUICKI) relative to baseline measurements. Fenofibrate therapy decreased total
      cholesterol, triglycerides by 29%, and triglycerides/HDL-cholesterol (all P<0.01)
      and improved flow-mediated dilation when compared with baseline. When compared
      with placebo and omega-3 fatty acids, fenofibrate therapy decreased non-HDL
      cholesterol (P<0.001) and triglycerides/HDL cholesterol (P=0.016) while
      increasing HDL cholesterol (P<0.001) and apolipoprotein AI (P=0.001). Of note,
      when compared with omega-3 fatty acids, fenofibrate therapy decreased fasting
      insulin (P=0.023) and increased plasma adiponectin (P=0.002) and insulin
      sensitivity (P=0.015). CONCLUSIONS: Omega-3 fatty acids and fenofibrate therapy
      promoted similar changes in triglycerides and endothelium-dependent dilation.
      However, fenofibrate therapy had substantially better effects on lipoprotein and
      metabolic profiles in patients with hypertriglyceridemia.

PMID- 22153697
TI  - Resveratrol increases the expression and activity of the low density lipoprotein
      receptor in hepatocytes by the proteolytic activation of the sterol regulatory
      element-binding proteins.
AB  - OBJECTIVE: The hepatocyte low density lipoprotein receptor (LDLR) plays a pivotal
      role in lipoprotein metabolism by lowering plasma LDL-cholesterol, a risk factor
      for atherosclerosis. The present study was conducted to investigate the effects
      of grape polyphenols on LDLR gene expression in human hepatocyte models. METHODS
      AND RESULTS: Among the 14 phenolic compounds in red wine, we found that a
      stilbene trans-resveratrol most strongly up-regulated LDLR gene expression in
      HepG2 cells. Trans-resveratrol increased the LDLR protein and uptake of
      fluorescent-labeled LDL. Moreover, it enhanced LDLR gene promoter activity
      through the proteolytic activation of the sterol regulatory element-binding
      protein-2 (SREBP-2) as well as SREBP-1. However, sterols completely abolished
      trans-resveratrol-induced SREBP activation and LDLR gene expression. Finally, AMP
      activated protein kinase (AMPK) knockdown analyses by siRNA revealed that AMPK
      activation was unnecessary for the effects of trans-resveratrol. CONCLUSIONS:
      Trans-resveratrol up-regulated hepatic LDLR expression via proteolytic activation
      of SREBPs. We concluded that trans-resveratrol exhibits the anti-atherogenic
      effect, at least in part, by increased hepatic LDLR expression and subsequent LDL
      uptake.

PMID- 22153698
TI  - Serum paraoxonase-3 concentration is associated with insulin sensitivity in
      peripheral artery disease and with inflammation in coronary artery disease.
AB  - OBJECTIVE: There are no data on the relationship between serum paraoxonase-3
      (PON3) concentration and atherosclerosis in humans. Our aim was to investigate
      possible associations, using recently developed methods, in patients with
      peripheral artery disease (PAD) or coronary artery disease (CAD). METHODS: We
      studied 118 PAD and 72 CAD patients and 175 healthy volunteers. Serum PON3 was
      determined by in-house ELISA using polyclonal antibodies generated against a
      synthetic peptide with a sequence specific to PON3. Polymorphisms of the PON3
      promoter were analysed by the Iplex Gold MassArrayTM method. RESULTS: There was a
      significant increase in serum PON3 concentration in both groups of patients with
      respect to the control group. In PAD patients, we observed significant positive
      correlations between PON3, insulin levels and HOMA index. These associations were
      not observed in CAD. There were significant positive associations between serum
      PON3 and beta-2-microglobulin, CCL2 and high-sensitivity C-reactive protein in
      CAD patients, but not in PAD. We did not find any significant differences in PON3
      gene promoter polymorphisms and their haplotypes between patients and controls,
      indicating that associations were not genetically determined. CONCLUSION: In both
      atherosclerotic phenotypes, serum PON3 concentration was increased, but this was
      associated with decreased insulin sensitivity in PAD and with inflammation in
      CAD.

PMID- 22153699
TI  - Variants within the nitric oxide synthase 1 gene are associated with stroke
      susceptibility.
AB  - OBJECTIVE: Animal studies have allowed important insights into the role of the
      nitric oxide synthase (NOS) enzymes in atherosclerosis and hypertension, as well
      as in stroke. In this study we tested the hypothesis that the NOS1 and NOS3
      genes, respectively encoding neuronal NOS (nNOS) and endothelial NOS (eNOS),
      influence stroke susceptibility and outcome after a stroke event. METHODS: We
      conducted a case-control association study in 551 ischemic stroke patients and
      530 controls to assess the role of NOS1 and NOS3 variants in stroke
      susceptibility. The same genes were tested for association with stroke outcome in
      a subset of 431 patients. RESULTS: Four NOS1 single nucleotide polymorphisms
      (SNPs) (rs2293050, rs2139733, rs7308402 and rs1483757) and four haplotypes were
      significantly associated with stroke susceptibility after adjusting for
      demographic, clinical and life-style risk factors, and correcting for multiple
      testing using the false discovery rate (FDR) method (SNPs:
      0.004<(uncorrected)P<0.007 and 0.036<FDR q<0.048; haplotypes:
      0.001<(uncorrected)P<0.010 and 0.018<FDR q<0.032). NOS1 variants were not
      associated with stroke outcome. We did not find any evidence for a role of the
      NOS3 gene in stroke susceptibility or outcome. CONCLUSION: Our results highlight
      NOS1 as a susceptibility factor for stroke, but do not corroborate previous NOS3
      association findings with stroke risk. nNOS is known to play a major role in
      atherosclerosis development and in blood flow regulation, and it is plausible
      that its influence in stroke may be mediated through these two main clinical risk
      factors.

PMID- 22153700
TI  - Deficiency of receptor-associated protein attenuates angiotensin II-induced
      atherosclerosis in hypercholesterolemic mice without influencing abdominal aortic
      aneurysms.
AB  - OBJECTIVE: Receptor-associated protein (RAP) was initially described as a
      regulator of low density lipoprotein receptor-related protein 1 (LRP1), but is
      now known to regulate many proteins. Since the direct effects of RAP on vascular
      pathologies have not been studied, this study determined whether RAP deficiency
      influenced angiotensin II (AngII)-induced atherosclerosis and abdominal aortic
      aneurysms (AAAs) in hypercholesterolemic mice. METHODS AND RESULTS: Male LDL
      receptor -/- mice that were either RAP +/+ or -/- were infused with AngII (500
      ng/kg/min) for 4 weeks while consuming a saturated fat-enriched diet. RAP
      deficiency had no effects on body weight or AngII-induced increases of systolic
      blood pressure. Despite increased plasma cholesterol concentrations, RAP
      deficiency reduced atherosclerotic lesion size in aortic arches, while having no
      effect on AngII-induced AAAs. RAP deficiency profoundly reduced LRP1 protein
      abundance in macrophages, but did not change its abundance in aortic smooth
      muscle cells. Also, RAP deficiency had no effects on mRNA abundance of LRP1 or
      lipoprotein lipase in macrophages. To determine whether RAP deficiency in
      leukocytes influenced AngII-induced atherosclerosis, irradiated male LDL receptor
      -/- mice were repopulated with bone marrow-derived cells from either RAP +/+ or 
      /- male mice. The chimeric mice were infused with AngII (500 ng/kg/min) for 4
      weeks while fed the saturated fat-enriched diet. RAP deficiency in bone marrow
      derived cells did not influence either plasma cholesterol concentrations or
      atherosclerotic lesion size. CONCLUSIONS: Whole body RAP deficiency attenuated
      atherosclerosis without influencing AAAs in hypercholesterolemic mice infused
      with AngII. The anti-atherogenic effect was not attributable to RAP deficiency in
      bone marrow-derived cells.

PMID- 22153701
TI  - Impact of a dedicated training program on the reproducibility of systolic
      dyssynchrony measures using tissue Doppler imaging.
AB  - BACKGROUND: The reproducibility of the measurement of mechanical dyssynchrony by
      echocardiography including Doppler tissue imaging has recently been questioned.
      The aim of this study was to ascertain the role of a dedicated training program
      to improve skills and the reproducibility of dyssynchrony assessment. METHODS: In
      70 patients with heart failure, color Doppler tissue images were acquired, and
      the time to peak systolic velocity of each segment and several dyssynchrony
      indices, including the standard deviation of time to peak systolic velocity, were
      measured by an expert to constitute a reference standard. The same images were
      then assessed by two beginners, who had only basic knowledge of dyssynchrony
      analysis after a 1-hour lecture, and two graduates, who had received a structured
      hands-on training program. Both sets of results were compared with the standard.
      RESULTS: For the standard deviation of time to peak systolic velocity, the linear
      correlations between the standard and beginner 1 (r = 0.643) and beginner 2 (r =
      0.532) were only modest (P < .001 for both). When referenced to the standard,
      interobserver variability was 18% for beginner 1 and 19% for beginner 2.
      Measurements with differences of >=10 msec were found in 24% and 22% of cases by
      beginners 1 and 2, respectively. In contrast, the assessments made by graduates 1
      and 2 were significantly improved. The correlation coefficients were 0.935 and
      0.929 (P < .001 for both), and interobserver variability values were 8% and 7%.
      The prevalence rates of measurements with differences >= 10 msec were 1.5% and
      3%, respectively. CONCLUSIONS: There is a learning curve for the measurement of
      systolic dyssynchrony using Doppler tissue imaging, but good reproducibility can
      be achieved by the use of a dedicated training program.

PMID- 22153702
TI  - Transient Hepatic Parenchymal Enhancement detected at dynamic imaging: a short
      instruction manual for the clinician.
AB  - Basic knowledge in the interpretation of hepatic imaging is essential for the
      clinical hepatologist. In recent years, the availability of dynamic imaging
      studies of the liver using computed tomography or magnetic resonance has led to
      appreciate the importance of early changes in arterial perfusion for the
      interpretation of hepatic lesions. Transient Hepatic Parenchymal Enhancement
      (THPE) is defined as a normal area of liver parenchyma that enhances after
      injection of contrast agent during the arterial phase of perfusion. Appearance of
      this sign is mostly associated with a reduction in portal perfusion or with
      inflammation, and appears in different morphologic patterns. THPE should not be
      considered a radiological artefact, and its interpretation is essential to avoid
      misclassification of hepatic lesions that may have clinical significance, such as
      hepatocellular carcinoma or hepatic metastases. In this short review we provide
      essential information on the causes, pathophysiology and morphology of THPE, and
      discuss the relevance of these findings in a clinical perspective.

PMID- 22153703
TI  - False positive galactomannan Platelia due to piperacillin-tazobactam.
AB  - INTRODUCTION: Invasive aspergillosis is a serious disease, the lethality of which
      is important among hematology patients. Early diagnosis is crucial for treatment
      options and the prognosis. Detection of the antigen galactomannan is the most
      frequently used microbiological tools. But galactomannan detection may be falsely
      positive, and this false positivity has been associated with piperacillin
      tazobactam treatment, the main antibiotic combination used in clinical
      hematology. OBJECTIVE: The purpose of our study, carried out from January 2009 to
      December 2010 at the Versailles hospital on in-patients with hematological
      disorders, was to evaluate the association between false galactomannan positivity
      and administration of piperacillin-tazobactam, and to study a possible
      variability of products issued by three manufacturers. PATIENTS AND METHOD: We
      noted that 207 patients were included (n=207), accounting for 69 false positive
      and 138 true negative results. The intrinsic galactomannan values in the study
      were sensitivity 100%, specificity 68%, positive and negative predictive values
      respectively 16%, 100%, and a likelihood positive and negative test at
      respectively 3.12, and 0. RESULTS: The statistical analysis did not determine any
      association between false positivity in galactomannan and piperacillin-tazobactam
      issued by two manufacturers (P=0.87 and P=0.94). But, there was a significant
      association between false galactomannan positivity and piperacillin-tazobactam
      issued by the third manufacturer (P=0.02). Four of the 25 batches issued by this
      manufacturer were tested and negative "in vitro" for galactomannan. DISCUSSION:
      This study results suggest that the association between false galactomannan
      positivity and piperacillin-tazobactam is not longer systematic, but can still
      prevail depending on the manufacturers. It also confirmed the positive
      contribution of testing piperacillin-tazobactam batches "in vitro" before using
      the antibiotic.

PMID- 22153704
TI  - [Multicenter study on lumbar puncture indication, clinical practice and
      feasibility].
AB  - INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers have been extensively studied
      as diagnostic markers for Alzheimer's disease (AD). However, results are variable
      probably due to lumbar puncture (LP) procedure, CSF collection and transport.
      This intercenter variability highlights the need for an efficient standardization
      of clinical and technical procedures. The aims of this study were firstly to
      compare the LP procedure and CSF transport process in all French Memory Centers
      and secondly to evaluate the incidence of LP side effects in 100 patients with
      cognitive disturbances. METHODS: LP practice and side effect prospective
      questionnaires were sent to all French Memory Centers in May 2010. Memory Centers
      were asked about their LP procedure. The prospective study over a three-week
      period has evaluated the LP feasibility and side effects. All data were collected
      until the end of July 2010. RESULTS: The answers of 18 out of 26 Memory Centers
      were collected. Although, these centers did not have the same LP procedure and
      CSF transport, the majority of them proceeded according to Innogenetics's advices
      concerning the use of polypropylene tubes and transport duration but not sample
      conditioning. Polypropylene tubes were different from one center to the other.
      CSF volume, pharmacological premedication and prevention of post-LP syndrome were
      variable in all responding centers. The prospective study carried out in 100
      patients revealed a very good LP acceptability (93/100 patients). LP feasibility
      was 97 % (90/93) and failed LP were consequently performed with success using
      radiological scopes. Three minor complications were observed. DISCUSSION AND
      CONCLUSION: All French Centers complied with Innogenetics' recommendations for
      pretechnical CSF procedures; however each Center put in place its own procedure
      that was different one center to the other. It will be very interesting to
      compare cut-off and result values for Abeta, tau and phosphorylated tau protein
      on threonine 181 between several centers that used their own procedures.
      Acceptability and safety were very good in our short but significant prospective
      study. These results confirm the data of Zetterberg et al., 2010.

PMID- 22153705
TI  - Contrast sensitivity evaluation in a population-based study in Shahroud, Iran.
AB  - PURPOSE: To determine the normal range of contrast sensitivity and its
      determinants through a population-based study in Shahroud, in northern Iran.
      DESIGN: Population-based cross-sectional study. PARTICIPANTS: Using random
      cluster sampling in Shahroud, 6311 people between 40 and 64 years of age were
      sampled; 5190 (82.24%) responded, and 965 participants were selected randomly for
      contrast sensitivity testing. METHODS: Participants underwent thorough eye
      examinations, including visual acuity and refraction tests, funduscopy, and slit
      lamp examination. MAIN OUTCOME MEASURES: Contrast sensitivity was tested with
      best correction using the CVS1000 grating charts (VectorVision, Inc., Greenville,
      OH), and results are reported here in log units. RESULTS: Overall, mean +/-
      standard deviation contrast sensitivity in spatial frequencies of 3, 6, 12, and
      18 cycles per degree was 1.62 +/- 0.19, 1.87 +/- 0.22, 1.53 +/- 0.28, and 1.09 +/
      0.30 log units, respectively. Contrast sensitivity worsened significantly with
      age and with lower levels of uncorrected visual acuity (P<0.001). Compared with
      men, contrast sensitivity was worse among women in spatial frequencies of 3 and
      6. Contrast sensitivity was significantly worse with myopia of more than 5.0
      diopters (P<0.001). There was an inverse correlation between the amount of
      astigmatism and contrast sensitivity in all spatial frequencies (P<0.001).
      Contrast sensitivity showed a significant variability among people with normal
      vision that increased at higher spatial frequencies. CONCLUSIONS: The present
      findings can be used as a reference guide for contrast sensitivity in a general
      population and for comparison in future studies. Contrast sensitivity declines
      with age, high myopia, and astigmatism. The wide range variability, even in the
      presence of normal visual acuity, should be considered when contrast sensitivity
      is tested.

PMID- 22153707
TI  - Randomized, controlled trial of a sustained delivery formulation of 5
      fluorouracil for the treatment of failing blebs.
AB  - PURPOSE: To determine the efficacy of a subconjunctival injection of hyaluronic
      acid (HA) with 5-fluorouracil (5FU) formulation as an adjunct in reviving bleb
      function by needling. DESIGN: Prospective, randomized, controlled trial.
      PARTICIPANTS: Fifty patients with previous trabeculectomy and scheduled by the
      managing physician for a needling intervention. METHODS: One eye of each patient
      was randomized to receive needling with HA-5FU mixture or needling with
      subconjunctival injection of 5FU solution alone. MAIN OUTCOME MEASURES: The
      primary outcome was the percentage of subjects with an intraocular pressure (IOP)
      <15 mmHg without any medications at 3 months. Secondary outcomes included the
      need for additional needling procedures and changes in bleb morphology. RESULTS:
      Forty-nine subjects (25 in the HA-5FU group and 24 in the 5FU group) completed 3
      months of follow-up. At baseline, there was no significant difference between the
      groups in terms of demographic features, subtype of glaucoma, vertical cup-to
      disc ratio, or visual field indices. The mean number of glaucoma medications at
      baseline was higher in the 5FU group (0.8+/-1.1 [mean +/- standard deviation] vs.
      0.2+/-0.6, P = 0.04). An IOP <15 mmHg without medications was reached in 48.0% of
      subjects in the HA-5FU group and in 33.3% of subjects in the 5FU group (P = 0.2).
      At 3 months, both groups demonstrated a significant decrease in IOP from baseline
      (HA-5FU: decrease of 5.9 mmHg [95% confidence interval, 3.4-8.4]; 5FU: decrease
      of 6.0 mmHg [95% confidence interval, 3.2-8.2]; P<0.001 for both). Intergroup
      comparisons for IOP change from baseline was not significant (P = 0.9). However,
      repeat needling was required more frequently in the 5FU group compared with the
      HA-5FU group (50.0% vs. 12.0%; P = 0.004). There were no significant differences
      in the number of reported adverse events, bleb vascularity, or morphology between
      the 2 groups. CONCLUSIONS: Subconjunctival injection of HA-5FU to revive bleb
      function after bleb needling is as effective as 5FU solution. Fewer repeat
      needlings were required after treatment with HA-5FU, suggesting that the use of a
      combined formulation of HA-5FU may improve the overall outcomes of bleb
      needlings.

PMID- 22153706
TI  - Validation of measurement scales in ocular graft-versus-host disease.
AB  - PURPOSE: To validate measurement scales for rating ocular chronic graft-versus
      host disease (GVHD) after allogeneic hematopoietic cell transplantation.
      Candidate scales were recommended for use in clinical trials by the National
      Institutes of Health (NIH) Chronic GVHD Consensus Conference or have been
      previously validated in dry eye syndromes. DESIGN: Prospective follow-up study.
      PARTICIPANTS: Between August 2007 and June 2010, the study enrolled 387 patients
      with chronic GVHD in a multicenter, prospective, observational cohort. METHODS:
      Using anchor-based methods, we compared clinician or patient-reported changes in
      eye symptoms (8-point scale) with calculated changes in 5 candidate scales: The
      NIH eye score, patient-reported global rating of eye symptoms, Lee eye subscale,
      Ocular Surface Disease Index, and Schirmer test. Change was examined for 333
      follow-up visits where both clinician and patient reported eye involvement at the
      previous visit. Linear mixed models were used to account for within-patient
      correlation. MAIN OUTCOME MEASURES: An 8-point scale of clinician or patient
      reported symptom change was used as an anchor to measure symptom changes at the
      follow-up visits. RESULTS: In serial evaluations, agreement regarding
      improvement, stability, or worsening between the clinician and patient was fair
      (weighted kappa = 0.34). Despite only fair agreement between evaluators, all
      scales except the Schirmer test correlated with both clinician-reported and
      patient-reported changes in ocular GVHD activity. Among all scales, changes in
      the NIH eye scores showed the greatest sensitivity to symptom change reported by
      clinicians or patients. CONCLUSIONS: Our results support the use of the NIH eye
      score as a sensitive measure of eye symptom changes in clinical trials assessing
      treatment of chronic GVHD.

PMID- 22153708
TI  - Facile synthesis of oxo-/thioxopyrimidines and tetrazoles C-C linked to sugars as
      novel non-toxic antioxidant acetylcholinesterase inhibitors.
AB  - Microwave-assisted synthesis of oxo-/thioxopyrimidines and tetrazoles linked to
      furanoses with D-xylo and D-ribo configuration, and to a D-galacto pyranose is
      reported and compared to conventional methods. Reaction of dialdofuranoses and
      dialdopyranoses with a beta-keto ester and urea or thiourea under microwave
      irradiation at 300 W gave in 10 min the target molecules containing the 2-oxo- or
      2-thioxo-pyrimidine ring in high yield. The tetrazole-derived compounds were
      obtained in two steps by reaction of the formyl group with hydroxylamine
      hydrochloride, copper sulfate, triethylamine and dicyclohexylcarbodiimide to give
      an intermediate nitrile, which was then treated with sodium azide. The use of
      microwave irradiation in the latter step also resulted in a considerably shorter
      reaction time (10 min) compared to hours under conventional heating to obtain a
      complete starting materials conversion. Acetylcholinesterase inhibition ranged
      from 20% to 80% for compounds concentration of 100 MUg/mL, demonstrating the
      potential of this family of compounds for the control of Alzheimer's disease
      symptoms. Most of the compounds showed antioxidant activity in the beta
      carotene/linoleic acid assay, some of them exhibiting IC(50) values in the same
      order of magnitude as those of gallic acid. The bioactive compounds did not show
      cytotoxic effects to human lymphocytes using the MTT method adapted for non
      adherent cells, nor genotoxicity determined by the short-term in vitro
      chromosomal aberration assay.

PMID- 22153709
TI  - A new approach for the determination of oligosaccharide structures.
AB  - A new method for the determination of oligosaccharide chains, known as the D60
      one-dimensional TOCSY method is introduced in this paper. The results show that
      the use of this method enables a more effective coherent long-range magnetic
      relay transfer compared with that of existing DIPSI-2 and MMDY methods. Further,
      the method is easy to use and is not sensitive to the error of the pulse width.
      Without complex z-filtering steps, the high-quality sub-spectrum of pure
      absorption can be quickly obtained, which facilitates sub-spectroscopy detection
      for the existence of weak spin-coupling sugar components in the saccharide ring.
      Glycosides are taken as examples to discuss the characteristics of this method
      and its application in the determination of oligosaccharides in spectrum peak
      height.

PMID- 22153710
TI  - The impact of metal sequestration on Staphylococcus aureus metabolism.
AB  - The Gram-positive pathogen Staphylococcus aureus poses a serious risk to public
      health due to its prevalence as a commensal organism, its ability to cause a
      multitude of diseases, and the increasing incidence of antibiotic resistant
      strains. S. aureus infects diverse niches within vertebrates despite being
      challenged by a robust immune response. The host-pathogen confrontation occurs in
      an environment nearly devoid of metals that are essential for bacterial
      proliferation. S. aureus is able to flourish in these conditions and often causes
      significant morbidity and mortality. This review highlights current themes
      pertaining to the process of host-mediated metal sequestration known as
      'nutritional immunity', S. aureus metal acquisition strategies, and how
      proliferating within a metal restricted environment impacts bacterial physiology.

PMID- 22153711
TI  - Model of interprofessional collaboration in the care of glaucoma patients and
      glaucoma suspects.

PMID- 22153713
TI  - Effect of temperature on the stability of various peptidases during peptide
      enriched soy sauce fermentation.
AB  - We previously developed a peptide-enriched soy sauce-like seasoning called
      Fermented Soybean Seasoning (FSS) with high-temperature fermentation, and we have
      reported the antihypertensive effects of FSS. Seryl-tyrosine (Ser-Tyr) and glycyl
      tyrosine (Gly-Tyr) were identified from FSS as active constituents in the
      antihypertensive effects. They were found to be particularly enriched in FSS;
      more so than in regular soy sauce. In the present study, we clarified one of the
      mechanisms underlying the accumulation of these bioactive peptides during high
      temperature soy sauce brewing. Crude enzyme extracts were prepared from model soy
      sauce mash (moromi) fermented at various temperatures. Leucine aminopeptidase-I,
      II, and seryl-tyrosine hydrolytic activity were found to decrease in the moromi
      incubated at the fermentation temperature of FSS whereas almost no decrease was
      observed in that of regular soy sauce. The concentrations of ACE inhibitory
      peptides, Ser-Tyr and Gly-Tyr, in the moromi incubated at high temperature were
      revealed to be higher than those at low temperature through quantitative LC-MS/MS
      analysis. These results suggested that the peptidases responsible for degrading
      low molecular weight bioactive peptides were inactivated during the high
      temperature fermentation, thus, these peptides would be likely to remain in the
      high temperature fermentation.

PMID- 22153714
TI  - Mechanical damage to Escherichia coli cells in a model of amino-acid crystal
      fermentation.
AB  - We investigated the mechanical damage to the Escherichia coli cell caused by
      polyvinyl chloride particles as a model of amino-acid crystal fermentation. Our
      results indicated that the glucose-consumption rate and the intracellular ATP
      concentration temporarily increased by the mechanical damage, and decreased after
      considerable damage had occurred on cell membrane.

PMID- 22153715
TI  - Effects of mixed feeder cells on the expansion of CD34+ cells.
AB  - Synergistic effects of mesenchymal stem cells (MSCs) isolated from bone marrow
      (BM), umbilical cord blood (UCB) and periosteum, and fibroblasts as mixed feeder
      cells (MFCs) on the expansion of hematopoietic progenitor cells (HPCs) were
      investigated in serum- and exogenous cytokine-free conditions. Enriched CD34(+)
      cells were cultured for 2weeks over the cell lines alone, individually, or
      selected combinations of them. When the cells were cultured over MFCs, the
      maximum increase in expansion of total nucleated cells and CD34(+)/CD38(-) cells
      was 157.3- and 128.6-fold, respectively. Furthermore, hematopoietic cytokine such
      as IL-6 and chemokines (e.g., IL-8, growth related oncogene (GRO), GRO-alpha,
      matrix metalloproteinase (MMP)-1, and MMP-3) were significantly increased in
      mixed feeder cells. Based on these results, MFCs can be more efficient for the ex
      vivo expansion of HPCs. These results strongly suggest that MFCs are more
      suitable for HPCs mass production.

PMID- 22153716
TI  - Orthotopic sigmoid vs. ileal neobladders in Japanese patients: a comparative
      assessment of complications, functional outcomes, and quality of life.
AB  - OBJECTIVES: To compare the clinical outcomes of sigmoid and ileal neobladders
      (NBs) created following radical cystectomy. MATERIALS AND METHODS: This study
      included 90 and 144 Japanese patients undergoing radical cystectomy and
      orthotopic NB reconstruction with a sigmoid and ileal segment, respectively.
      Postoperative clinical outcomes between the sigmoid and ileal NB groups (SNBG and
      INBG) were compared. RESULTS: In this series, 110 early and 51 late complications
      occurred in 71 and 41 patients, respectively; however, there was no significant
      difference in the incidence of complications between SNBG and INBG. At 1 year
      postoperatively, there were no significant differences in the proportion of
      spontaneous voiders and the continence status between these 2 groups; however,
      despite the lack of significant differences in the maximal flow rate and voided
      volume, the post-void residual in SNBG was significantly smaller than that in
      INBG. Voiding functional outcomes at 5 years postoperatively were also obtained
      from 28 and 49 in SNBG and INBG, respectively. Although there were no significant
      changes in the functional outcomes in SNBG, the proportion of spontaneous voiders
      and post-void residual in INBG at 5 years postoperatively were significantly
      poorer than those at 1 year postoperatively. Furthermore, the postoperative
      health-related quality of life assessed by a Short-Form 36 survey did not show
      any significant differences in all 8 scores between these 2 groups. CONCLUSIONS:
      Both types of NB reconstruction resulted in comparatively satisfactory outcomes;
      however, the voiding function, particularly that on long-term follow-up, in SNBG
      appeared to be more favorable than that in INBG.

PMID- 22153717
TI  - The influence of pigments on the slow crack growth in dental zirconia.
AB  - OBJECTIVES: Partially yttria stabilized zirconium oxide was introduced as core
      material for core-veneered full ceramic dental restorations, because of its
      biological inertness, high mechanical strength, and toughness. In order to
      improve the esthetical possibilities pigments in the core are introduced, that
      might influence the stabilization by yttrium. METHODS: Double torsion tests were
      performed to study the influence of the pigments in the core ceramics on its
      fracture toughness. RESULTS: A significant difference was observed in the stress
      intensity factor (K(10)) as well as in the R-curve behavior between the ceramic
      with and without pigment. SIGNIFICANCE: The lower stress intensity factor for the
      ceramic with pigment could affect the clinical performance of dental zirconia
      restorations with this material.

PMID- 22153718
TI  - Influence of zirconia framework thickness on residual stress profile in veneering
      ceramic: measurement by hole-drilling.
AB  - OBJECTIVES: Framework design is reported to influence chipping in zirconia-based
      restorations, which is an important cause of failure of such restorations.
      Residual stress profile in the veneering ceramic after the manufacturing process
      is an important predictive factor of the mechanical behavior of the material. The
      objective of this study is to investigate the influence of framework thickness on
      the stress profile measured in zirconia-based structures. METHODS: The stress
      profile was measured with the hole-drilling method in bilayered disc samples of
      20mm diameter with a 1.5 mm thick veneering ceramic layer. Six different
      framework thicknesses from 0.5 mm to 3 mm were studied. Two different cooling
      procedures were also investigated. RESULTS: Compressive stresses were observed in
      the surface, and tensile stresses in the depth of most of the samples. The slow
      cooling procedure was found to promote the development of interior tensile
      stresses, except for the sample with a 3mm thick framework. With the tempering
      procedure, samples with a 1.5 mm thick framework exhibited the most favorable
      stress profile, while thicker and thinner frameworks exhibited respectively in
      surface or interior tensile stresses. SIGNIFICANCE: The measurements performed
      highlight the importance of framework thickness, which determine the nature of
      stresses and can explain clinical failures encountered, especially with thin
      frameworks. The adequate ratio between veneering ceramic and zirconia is hard to
      define, restricting the range of indications of zirconia-based restorations until
      a better understanding of such a delicate veneering process is achieved.

PMID- 22153720
TI  - Corticosteroid effects on calcium signaling in limbic neurons.
AB  - Corticosteroid hormones, which are released in high amounts after stress, easily
      pass the blood-brain-barrier. In the brain they bind to intracellular receptors
      which act as transcriptional regulators. These receptors are highly expressed in
      neurons of the hippocampal formation and the amygdala, areas that play a role in
      (emotional) memory formation. Voltage gated Ca(2+) channels are among the most
      prominent targets of corticosteroid hormones. When the levels of corticosterone -
      the prevalent corticosteroid in rats and mice- are low, L-type Ca(2+) currents of
      CA1 hippocampal cells are small. However, when hormone levels rise e.g. after
      stress, the amplitude of L-type Ca(2+) currents will be slowly enhanced, through
      a process requiring DNA binding of glucocorticoid receptor homodimers. Kinetic
      properties and voltage dependency of the currents remain unchanged. Neurons in
      the basolateral amygdala respond in a comparable fashion, but Ca(2+) currents of
      neurons in the dentate gyrus are unaffected by corticosteroids. The stress
      induced increase in Ca(2+) influx has considerable functional consequences in
      health and disease. At the short term, i.e. 1-4h after stress, the enhanced
      Ca(2+) influx contributes to stronger firing frequency accommodation and a higher
      threshold for the induction of long-term potentiation. This helps to normalize
      neuronal activity after stress and presumably protects earlier encoded, stress
      related information. At the longer term, though, increased Ca(2+) load may impose
      a risk, increasing the vulnerability of limbic cells to additional challenges
      e.g. during epileptic or ischemic episodes.

PMID- 22153719
TI  - Targeting Src family kinases in anti-cancer therapies: turning promise into
      triumph.
AB  - Src is a non-receptor tyrosine kinase that is deregulated in many types of
      cancer. Decades of research have revealed the crucial role of Src in many aspects
      of tumor development, including proliferation, survival, adhesion, migration,
      invasion and, most importantly, metastasis, in multiple tumor types. Despite
      extensive preclinical evidence that warrants targeting Src as a promising
      therapeutic approach for cancer, Src inhibitor(s) showed only minimal therapeutic
      activity in various types of solid tumors when used as a single agent in recent
      early-phase clinical trials. In this review, we highlight the most recent
      advances from preclinical studies and clinical trials that shed light on
      potential clinical use of Src inhibitor-containing combinatorial regimens in
      overcoming resistance to current anticancer therapies and in preventing
      metastatic recurrence.

PMID- 22153721
TI  - Dual anterior and posterior mitral valve clefts evaluated by 3-dimensional
      echocardiography with robot-assisted surgical correction.

PMID- 22153723
TI  - Younger age and valve oversizing are predictors of structural valve deterioration
      after pulmonary valve replacement in patients with tetralogy of Fallot.
AB  - OBJECTIVE: We sought to identify predictors of structural valve deterioration
      after pulmonary valve replacement in patients with tetralogy of Fallot. METHODS:
      A retrospective review of 227 patients with tetralogy of Fallot who underwent
      stented bioprosthetic pulmonary valve replacement at Children's Hospital Boston
      between 1994 and 2009 was performed. Patient and valve characteristics were
      assessed as potential predictors of structural valve deterioration by using
      univariate and multivariable analysis. Freedom from pulmonary valve
      reintervention and structural valve deterioration were determined by using Kaplan
      Meier analysis. RESULTS: Two hundred twenty-nine pulmonary valve replacement
      operations were performed, with no early mortalities. Freedom from reintervention
      and structural valve deterioration were 94% (95% confidence interval, 87%-100%)
      and 74% (95% confidence interval, 63%-85%) at 5 years, respectively, and median
      time to reintervention was 6.4 years (range, 2-10.1 years). Younger age and
      higher indexed valve internal diameter were predictors of reduced time to
      structural valve deterioration. Among patients aged less than 20 years at the
      time of pulmonary valve replacement, indexed valve internal diameter was a
      significant predictor of increased risk of structural valve deterioration. Valve
      manufacturer was not a significant predictor of structural valve deterioration.
      CONCLUSIONS: Younger age at the time of pulmonary valve replacement and valve
      oversizing in patients less than 20 years of age at the time of pulmonary valve
      replacement were significant predictors of structural valve deterioration and
      could potentially affect the timing of pulmonary valve replacement and the extent
      of valve oversizing in small children. No statistically significant difference in
      valve performance was seen between bioprosthetic valve types at short-term follow
      up.

PMID- 22153724
TI  - Assessing health care planning--a framework-led comparison of Germany and New
      Zealand.
AB  - OBJECTIVES: With markets and competition dominating much of the debate on health
      care reform, health care planning has received little scholarly attention in
      recent years. Yet in many high-income countries, governments have continued to
      plan some elements of their health care systems. We use a new framework for
      analysing health care planning organised around the dimensions of 'vision',
      'governance' and 'intelligence' to assess the approach in two deliberately
      contrasting countries, Germany and New Zealand. METHODS: A review of the
      literature on health care planning in general and specifically in Germany and New
      Zealand, supported by key participant interviews. RESULTS: Planning in both
      countries largely reflects the different institutional arrangements of their
      wider health systems. Planning in Germany is fragmented, in part due to
      federalism and corporatism, with separate approaches in different health care
      sectors and regions. In contrast, New Zealand's NHS-style health system favours a
      more hierarchical, integrated approach, with clear lines of accountability, and
      central government capacity to define objectives and monitor developments. Both
      countries find it difficult to use planning to align demand for and supply of
      health care though New Zealand makes some use of population needs assessments to
      support this process while these are currently absent in Germany. CONCLUSIONS:
      While it remains challenging to compare health care systems that are
      institutionally very different, this new framework for analysing their approaches
      to planning draws attention to their advantages and disadvantages. It also
      generates an agenda for future research to improve our understanding of the role
      and effectiveness of different forms of planning versus, and in combination with,
      other policy tools to relating health care supply and demand.

PMID- 22153725
TI  - Assessment of silent microembolism by magnetic resonance imaging after
      cardioversion in atrial fibrillation.
AB  - INTRODUCTION AND OBJECTIVES: To study electrical cardioversion in patients with
      atrial fibrillation as a potential cause of acute ischemic brain lesions.
      METHODS: We performed prospective analysis of 62 consecutive patients (62 [10]
      years, 16 female). All of them were anticoagulated for at least 3 weeks with an
      international normalized ratio of 2.69 (0.66). In all cases a magnetic resonance
      imaging of the brain was performed before and 24h after the cardioversion,
      including diffusion-weighted sequences. A neurological exploration was also
      performed before and after the procedure, using the modified Ictus on the
      National Institute of Health Stroke Scale and the modified Rankin scale. Written
      informed consent was obtained in all cases. RESULTS: Of the 62 patients, 51 (85%)
      reverted to sinus rhythm. The neurological examination showed no changes after
      cardioversion. The pre-procedure magnetic resonance imaging showed microvascular
      disease in 35 (56%), including 2 patients with known cerebrovascular disease, and
      did not depict new clinically silent ischemic areas after cardioversion.
      CONCLUSIONS: After electrical cardioversion no acute ischemic lesions in the
      brain nor alteration in the neurological scales were found. Nevertheless, in 35
      patients (56%) with persistent atrial fibrillation, the magnetic resonance
      imaging showed clinically silent ischemic lesions.

PMID- 22153726
TI  - Lifestyle changes lower FABP4 plasma concentration in patients with
      cardiovascular risk.
AB  - INTRODUCTION AND OBJECTIVES: To analyze the impact of lifestyle changes on
      adipocyte fatty acid-binding protein (FABP4) plasma levels in patients with
      cardiovascular risk. METHODS: A 1-year prospective study enrolled 140 patients
      with cardiovascular risk but without previous cardiovascular disease to evaluate
      the impact of therapeutic lifestyle changes on cardiovascular risk, focusing on
      tobacco, nutrition education, and physical activity. RESULTS: The FABP4 variation
      was inversely associated to physical activity changes (MET.h/wk). FABP4
      significantly decreased in patients with increased physical activity, whereas it
      increased with physical activity reduction. These FABP4 changes were also
      associated with modifications in body mass index and insulin resistance
      parameters; however, the correlations between physical activity and FABP4
      remained after adjusting for these confounding variables. Changes in physical
      activity were the main predictors of FABP4 modifications. FABP4 reductions were
      directly associated with low-density lipoprotein-cholesterol and apolipoprotein B
      reductions. Neither tobacco cessation nor diet composition modified FABP4
      concentrations. CONCLUSIONS: Increasing aerobic physical activity can decrease
      FABP4 plasma levels, independently of weight reduction. If a causal role of FABP4
      in metabolic and vascular alterations could be established, our results would add
      new positive effects on metabolic and cardiovascular risk of both physical
      activity and avoiding obesity.

PMID- 22153727
TI  - Safety and efficacy of endothelial progenitor cell capture stent in ST-elevation
      acute myocardial infarction. GENIA Study.

PMID- 22153728
TI  - Characteristics associated with use of homeopathic drugs for psychiatric symptoms
      in the general population.
AB  - OBJECTIVE: To explore which patient characteristics are associated in
      naturalistic conditions with the lifetime use of homeopathic treatment for
      psychiatric symptoms. METHOD: Lifetime use of psychotropic treatment was explored
      in a sample of 36,785 persons, participating in the Mental Health Survey in the
      General Population. Characteristics associated with use of homeopathic
      treatments, associated or not with conventional psychotropic drugs, were explored
      using multivariate analyses. RESULTS: Use of homeopathic treatment for
      psychiatric symptoms was reported by 1.3% of persons. Younger age, female gender
      and high educational level were associated with use of homeopathy. Half of
      homeopathy users presented at least one Mini International Neuropsychiatric
      Interview (MINI) diagnosis, most frequently anxiety disorders. Their diagnostic
      profile was similar to that of persons reporting use of anxiolytics or hypnotics.
      Compared to persons with no lifetime use of psychotropic drugs, persons using
      homeopathy were more likely to present with a diagnosis of mood disorder or
      anxiety disorder. Compared to those using conventional psychotropic drugs, they
      presented less frequently with psychiatric disorders, with the exception of
      anxiety disorders. CONCLUSION: Homeopathic treatment for psychiatric symptoms
      appears to be used mainly to reduce anxiety symptoms in the general population.

PMID- 22153729
TI  - Socio-economic disadvantage and delusional-like experiences: a nationwide
      population-based study.
AB  - PURPOSE: Delusional-like experiences (DLE) have been associated with low income,
      suggesting that more broadly defined socio-economic disadvantage may be
      associated with these experiences. We had the opportunity to explore the
      association between DLE and both individual- and area-level measures of socio
      economic disadvantage. METHOD: Subjects were drawn from the Australian National
      Survey of Mental Health and Wellbeing 2007. The Composite International
      Diagnostic Interview was used to identify DLE, common psychiatric disorders, and
      physical disorders. Individual-level and area-level socio-economic disadvantage
      measures were available based on variables including income, educational
      attainment, employment status, and housing. We examined the relationship between
      the variables of interest using logistic regression, adjusting for potential
      confounding factors. RESULTS: Of the 8773 subjects, 8.4% (n=776) positively
      endorsed one or more DLE. DLE screen items were more likely to be endorsed by
      those who were (a) younger, (b) never married, or widowed, separated or divorced
      status, (c) migrants, or (d) living in rented houses. There were significant
      associations between socio-economic disadvantage and increased DLE endorsement,
      and this was found for both individual-level and area-level measures of socio
      economic disadvantage. In general, the associations remained significant after
      adjusting for a range of potential confounding factors and in planned sensitivity
      analyses. CONCLUSIONS: DLE are associated with socio-economic disadvantage in the
      general population. We speculate that the link between socio-economic
      disadvantage and DLE may be mediated by psychosocial stress and general
      psychological distress.

PMID- 22153730
TI  - Neurocognitive effectiveness of quetiapine, olanzapine, risperidone, and
      ziprasidone: a pragmatic, randomized trial.
AB  - PURPOSE: Cognitive effects of second generation antipsychotics (SGAs) are
      indicated in efficacy studies but the generalizability of the results may be
      limited by rigid designs and selected samples. The aim of this naturalistic,
      industry-independent study is to investigate whether differential neurocognitive
      effectiveness can be found among olanzapine, quetiapine, risperidone, and
      ziprasidone in a clinically relevant sample with psychosis. SUBJECTS AND METHODS:
      Adult patients acutely admitted to an emergency ward for psychosis were
      randomized to risperidone, olanzapine, quetiapine or ziprasidone and followed for
      up to 2 years. Participants were assessed repeatedly using the Positive and
      Negative Syndrome Scale and a repeatable neurocognitive test battery. RESULTS: A
      total of 226 patients were included and 171 patients underwent neurocognitive
      assessments. The sample had a global cognitive performance score at baseline
      about one standard deviation below that of the general population. The
      ziprasidone group had the fastest increase in global functioning which was
      significantly superior to that of the olanzapine group for the entire follow-up
      period. Before 90 days, the quetiapine group had the fastest increase which was
      statistically superior to the olanzapine group. DISCUSSION: Ziprasidone and
      quetiapine demonstrated superiority to olanzapine in increasing global
      neurocognitive performance in this naturalistic sample.

PMID- 22153731
TI  - The association between Internet addiction and psychiatric disorder: a review of
      the literature.
AB  - Internet addiction is a newly emergent disorder. It has been found to be
      associated with a variety of psychiatric disorders. Information about such
      coexisting psychiatric disorders is essential to understand the mechanism of
      Internet addiction. In this review, we have recruited articles mentioning
      coexisting psychiatric disorders of Internet addiction from the PubMed database
      as at November 3, 2009. We describe the updated results for such disorders of
      Internet addiction, which include substance use disorder, attention-deficit
      hyperactivity disorder, depression, hostility, and social anxiety disorder. We
      also provide discussion for possible mechanisms accounting for the coexistence of
      psychiatric disorders and Internet addiction. The review might suggest that
      combined psychiatric disorders mentioned above should be evaluated and treated to
      prevent their deteriorating effect on the prognosis of Internet addiction. On the
      other hand, Internet addiction should be paid more attention to when treating
      people with these coexisting psychiatric disorders of Internet addiction.
      Additionally, we also suggest future necessary research directions that could
      provide further important information for the understanding of this issue.

PMID- 22153732
TI  - Variation in the BDNF Val66Met polymorphism and response to cognitive-behavior
      therapy in obsessive-compulsive disorder.
AB  - BACKGROUND: Recent research suggests that the brain-derived neurotrophic factor
      (BDNF) may play a role in extinction learning. The goal of this study was to test
      whether variation in the BDNF Val66Met polymorphism is related to treatment
      response to exposure-based cognitive-behavior therapy (CBT), a form of extinction
      learning, in obsessive-compulsive disorder (OCD). METHODS: One hundred and six
      OCD patients from a specialized clinic, who underwent a standardized CBT
      treatment after partial or non-response to a 12-week pharmacological trial, were
      genotyped for the BDNF Val66Met and the relationship between genotype and
      treatment response was analyzed. RESULTS: Among 98 CBT completers, 36% of those
      carrying the BDNF Met allele were rated as CBT responders compared to 60% of
      nonMet allele carriers (P=0.027). When analyzing the different obsessive
      compulsive symptom dimensions, in patients with contamination/cleaning symptoms,
      the Met allele was associated with a significantly worse CBT response (P<0.0001)
      and a lower obsessions severity decrease from pre- to posttreatment (P=0.046).
      CONCLUSION: Genetic variation in BDNF may be associated with treatment response
      in exposure-based CBT in OCD, especially in those patients exhibiting
      contamination/cleaning symptoms.

PMID- 22153733
TI  - Simulations in obstetrics.

PMID- 22153734
TI  - Simulation in neonatal resuscitation.

PMID- 22153735
TI  - "Not little adults": pediatric considerations in medical simulation.

PMID- 22153736
TI  - Simulation training in surgery.

PMID- 22153737
TI  - Simulation for physician extenders.

PMID- 22153738
TI  - Innovative simulation training models.

PMID- 22153739
TI  - Fluorescence of Zn-Al-Eu ternary layered hydroxide response to phenylalanine.
AB  - We reported the fluorescence of a Zn-Al-Eu ternary layered double hydroxide (LDH)
      response to an amino acid (phenylalanine) for the first time. As shown in
      fluorescence, the red emissions attributed to (5)D(0)-(7)F(J) transitions (J=1,
      2, 3, 4) of Eu(3+) ions were quenched by the phenylalanine (Phe), and a strong
      blue emission at around 445 nm appeared. The fluorescent changes may be due to
      ligand-to-metal charges transfer, which was caused by the interaction between the
      Zn-Al-Eu LDH and Phe. This interaction was manifested by markedly different
      chemical shift positions of the Zn 3p(3/2), Al 2p, Eu 4d(3/2), O 1s, and C 1s
      peaks in the XPS spectra from those of the Zn-Al-Eu LDH and Zn-Al-Eu/Phe
      composite. Furthermore, the interaction between the LDH and Phe was supported by
      the results of X-ray diffraction (XRD) measurements, Fourier transform infrared
      (FT-IR) spectra, and thermogravimetric and differential thermogravimetric (TG
      DTG) analysis. The fluorescence of Zn-Al-Eu LDH response to Phe may be potential
      application in biological techniques.

PMID- 22153740
TI  - Molecular structure of 2-chloromethyl-1H-benzimidazole hydrochloride: single
      crystal, spectral, biological studies, and DFT calculations.
AB  - In the present work, structural studies on 2-chloromethyl-1H-benzimidazole
      hydrochloride have been performed extensively by X-ray crystallography, (1)H NMR,
      FT-IR, UV/vis, and elemental analysis. The title compound crystallizes in a
      monoclinic space group P2(1)/c with a=7.1982 (3) A, b=9.4513 (5) A, c=14.0485 (7)
      A and beta=102.440 (3) degrees  forming an infinite chain structure parallel to
      "b" axis through the intermolecular hydrogen bond. Optimized geometrical
      structure, harmonic vibrational frequencies, natural bonding orbital (NBO) and
      frontier molecular orbitals (FMO) were obtained by DFT/B3LYP method combined with
      6-31G(d) basis set. TD-DFT calculations help to assign the electronic
      transitions. The (1)H NMR chemical shifts were computed at the B3LYP/6
      311+G(2d,p) level of theory in different solvents by applying GIAO method using
      the polarizable continuum model (PCM). The title compound was screened for its
      antibacterial activity referring to Tetracycline as a standard antibacterial
      agent.

PMID- 22153741
TI  - FT-IR, FT-Raman, UV spectra and DFT calculations on monomeric and dimeric
      structure of 2-amino-5-bromobenzoic acid.
AB  - In this work, the molecular conformation, vibrational and electronic transition
      analysis of 2-amino-5-bromobenzoic acid (2A5BrBA) were presented for the ground
      state using experimental techniques (FT-IR, FT-Raman and UV) and density
      functional theory (DFT) employing B3LYP exchange correlation with the 6
      311++G(d,p) basis set. FT-IR and FT-Raman spectra were recorded in the regions of
      400-4000 cm(-1) and 50-4000 cm(-1), respectively. There are four conformers, C1,
      C2, C3 and C4 for this molecule. The geometrical parameters, energies and
      wavenumbers have been obtained for all four conformers. The computational results
      diagnose the most stable conformer of 2A5BrBA as the C1 form. The complete
      assignments of fundamental vibrations were performed on the basis of the total
      energy distribution (TED) of the vibrational modes, calculated with scaled
      quantum mechanics (SQM) method. Raman activities calculated by DFT method have
      been converted to the corresponding Raman intensities using Raman scattering
      theory. The UV spectra of investigated compound were recorded in the region of
      200-400 nm for ethanol and water solutions. The electronic properties were
      evaluated with help of time-dependent DFT (TD-DFT) theoretically and results were
      compared with experimental observations. The thermodynamic properties of the
      studied compound at different temperatures were calculated, revealing the
      correlations between standard heat capacity, standard entropy, standard enthalpy
      changes and temperatures. The observed and the calculated geometric parameters,
      vibrational wavenumbers and electronic transitions were compared with observed
      data and found to be in good agreement.

PMID- 22153742
TI  - Synthesis and structural characterization of ternary Cu (II) complexes of glycine
      with 2,2'-bipyridine and 2,2'-dipyridylamine. The DNA-binding studies and
      biological activity.
AB  - In this study two new complexes [Cu(bpy)(Gly)Cl].2H(2)O (1) and
      [Cu(dpa)(Gly)Cl].2H(2)O (2) (bpy=2,2'-bipyridine; dpa=2,2'-dipyridylamine,
      Gly=glycine) have been synthesized and characterized by elemental analysis, IR,
      TGA, UV-vis and magnetic susceptibility measurements. The binding properties of
      the complexes with CT-DNA were investigated by electronic absorption spectra. The
      intrinsic binding constants (K(b)) calculated from UV-vis absorption studies were
      1.84 * 10(3) M(-1) and 3.1 * 10(3) M(-1) for complexes 1 and 2 respectively.
      Thermal denaturation has been systematically studied by spectrophotometric method
      and the calculated DeltaT(m) was nearly 5  degrees C for each complex. All the
      results suggest that the interaction modes between the complexes and CT-DNA were
      electrostatic and/or groove binding. The redox behavior of the two complexes was
      investigated by cyclic voltammetry. Both complexes, in presence and absence of CT
      DNA show a quasi-reversible wave corresponding to Cu(II)/Cu(I) redox couple. The
      change in E(1/2), DeltaE and I(pc)/I(pa) ascertain the interaction of complexes 1
      and 2 with CT-DNA. Further insight into the binding of complexes with CT-DNA has
      been made by gel electrophoresis, where the binding of complexes is confirmed
      through decreasing the mobility and intensity of DNA bands. In addition, the
      antitumor activity of the complexes was tested on two cancer cell lines; the
      breast cancer (MCF7) and the human hepatocellular carcinoma (HEPG2), as well as
      one normal cell line; the human normal melanocytes (HFB4). The results showed
      that complex 1 was more potent antitumor agent than complex 2. The in-vitro
      antimicrobial activity of the two complexes was carried out using the disc
      diffusion method against different species of pathogenic bacteria and fungi. The
      activity data showed that complex 2 was more active in inhibiting the growth of
      the tested organisms.

PMID- 22153743
TI  - Substituent and solvent effects on intramolecular charge transfer of 5-arylidene
      2,4-thiazolidinediones.
AB  - The absorption spectra of twelve 5-arylidene-2,4-thiazolidinediones were recorded
      in twenty one solvents in the range from 300 to 600 nm. The effect of specific
      and non-specific solvent-solute interactions on the absorption maxima shifts were
      evaluated by using the Catalan solvent parameter set. Furthermore, the
      experimental findings were interpreted with the aid of ab initio MP2 and time
      dependent density functional (TD-DFT) methods. It was found that different
      substituents significantly change the extent of conjugation in the molecules and
      further affect their intramolecular charge transfer character.

PMID- 22153744
TI  - Nucleic acid interaction and antibacterial behaviours of a ternary palladium(II)
      complexes.
AB  - The bidentate ligands and Pd(II) complexes have been synthesized and
      characterized using elemental analysis (C, H, N), (1)H NMR, (13)C NMR, electronic
      spectra, FT-IR and FAB mass spectroscopy. The binding of palladium complexes with
      calf thymus DNA (CT DNA) has been explored using absorption titration, DNA
      melting temperature and viscosity measurements. The cleavage reaction on pUC19
      DNA has been monitored by agarose gel electrophoresis. The results suggest that
      complexes can bind to DNA by intercalative modes and exhibit nuclease activities
      in which supercoil form is converted to open circular form. The antibacterial
      activity of ligands and complexes has been performed against three Gram(-ve) and
      two Gram(+ve) microorganisms and the study indicates that all the complexes show
      better microbial inhibition activity than ligands and palladium salt.

PMID- 22153745
TI  - Role of contrast-enhanced ultrasound in decision support for diagnosis and
      treatment of hepatic artery thrombosis after liver transplantation.
AB  - OBJECTIVE: To assess role of contrast-enhanced ultrasound (CEUS) in decision
      support for diagnosis and treatment of hepatic artery thrombosis (HAT) after
      liver transplantation. MATERIALS AND METHODS: Between January 2005 and January
      2011, 605 patients underwent liver transplantation in our medical center. All the
      liver transplant recipients received Doppler ultrasound scanning and CEUS
      examination was performed in 45 patients with suspected HAT on Doppler
      ultrasound. Sensitivity, specificity, accuracy, positive predict value and
      negative predictive value of CEUS in diagnosing HAT were determined based on the
      results from angiography, surgery and clinical follow-up. RESULTS: Fourteen HATs,
      including one late HAT, were diagnosed by CEUS. Twelve HAT cases were confirmed
      by angiographic and/or surgical findings, while the late HAT and other 31
      patients with negative CEUS finding were confirmed by the clinical follow-up.
      There was a false positive HAT diagnosed by CEUS in which angiography revealed a
      patent hepatic artery. The sensitivity, specificity, accuracy, positive predict
      value and negative predictive value of CEUS in diagnosing HAT were 100%, 96.9%,
      97.8%, 92.9% and 100%, respectively. In our series of 605 liver transplants, the
      incidence and mortality of HAT was 2.2% (13/605) and 53.8% (7/13), respectively.
      CONCLUSIONS: Our study demonstrates the important role of CEUS in decision
      support for diagnosis and treatment of HAT after liver transplantation. When HAT
      is suspected by Doppler ultrasound, CEUS shall immediately be performed to
      elucidate its nature. A negative CEUS finding shall avoid invasive angiography.
      Such as, CEUS may alter the clinical workflow on HAT detection after liver
      transplantation.

PMID- 22153746
TI  - Dual energy spectral CT imaging of insulinoma-Value in preoperative diagnosis
      compared with conventional multi-detector CT.
AB  - OBJECTIVE: The aim of this study was to investigate the value of dual energy
      spectral CT (DEsCT) imaging in preoperative diagnosis of insulinomas in
      comparison with conventional multi-detector CT (MDCT). MATERIALS AND METHODS:
      Thirty-five patients were included in this study with 14 underwent the
      conventional dual-phase CT imaging (from March 2009 to January 2010) and 21
      underwent the dual-phase DEsCT imaging (from February 2010 to May 2011). CT
      images were interpreted prospectively by two radiologists in consensus before
      operation. All the patients had diagnosis confirmed pathologically. The accuracy
      of preoperative diagnosis of insulinomas between DEsCT imaging and conventional
      MDCT, and between different kinds of images of DEsCT was compared. RESULTS: There
      were 39 confirmed lesions among the 35 patients (23 and 16 tumors in the spectral
      CT group and MDCT group, respectively). MDCT detected 11 of 16 tumors. DEsCT
      imaging detected 20 of 23 tumors separately with the monochromatic image or the
      iodine density image, and 22 of 23 tumors with the combination of the two kinds
      of images. The sensitivity for the preoperative diagnosis of insulinoma was 95.7%
      with the combination of monochromatic and iodine density images in DEsCT imaging,
      statistically higher than that with the conventional MDCT (68.8%) (p=0.033).
      CONCLUSION: Dual energy spectral CT imaging has higher sensitivity in
      preoperative diagnosis of insulinomas compared with conventional MDCT. The
      combination of monochromatic image and iodine density image can improve the
      diagnostic sensitivity of insulinomas.

PMID- 22153747
TI  - T1rho and T2 mapping of the proximal tibiofibular joint in relation to aging and
      cartilage degeneration.
AB  - OBJECTIVE: To study the effects of aging and cartilage degeneration of the
      proximal tibiofibular- and femorotibial joint (PTFJ, FTJ) on the cartilage of the
      PTFJ using T(1)rho and T(2) mapping. MATERIALS AND METHODS: We performed sagittal
      T(1)rho and T(2) mapping of the PTFJ and FTJ on 55 subjects with knee disorders.
      We placed 3 regions of interest (ROIs) on images of the cartilage in the PTFJ,
      medial femoral condyle (MFC), and medial tibia plateau (MTP). Correlation
      analysis was performed for the T(1)rho and T(2) values of each ROI and the
      patient age and the osteoarthritic grade of the PTFJ and FTJ. RESULTS: The
      T(1)rho and T(2) values of the PTFJ were affected neither by aging nor the
      osteoarthritic grade of the FTJ. Values of the FTJ normalized to PTFJ values were
      correlated with the osteoarthritic grade of the FTJ in the MFC (r=0.851 and
      0.779, respectively) and the MTP (r=0.635 and 0.762, respectively). There was a
      significant difference in the T(1)rho but not the T(2) value of the PTFJ and MFC
      between normal and mildly osteoarthritic cartilage of each joint. CONCLUSION: We
      document that the T(1)rho and T(2) values of PTFJ cartilage were not affected by
      aging or cartilage degeneration in the FTJ. The T(1)rho value of the PTFJ may
      represent a useful internal standard reference for evaluating early degeneration
      of the FTJ.

PMID- 22153748
TI  - High dose artesunate in combination with mefloquine: pharmacovigilance in the
      Venezuelan Amazon.
AB  - Forty-six patients in a remote health post of Amazonas, Venezuela, accidentally
      received artesunate in a dose of 10 mg/kg/day combined with mefloquine. This
      corresponds to the upper limit of the therapeutic range recommended by the WHO (2
      10 mg/kg/day). Side effects were retrospectively investigated and a
      pharmacovigilance report was written. The main side effects were vomiting and
      diarrhea. Four patients developed complications with signs of dehydration. It is
      suggested to re-assess the therapeutic range of artesunate when given in
      combination with mefloquine and to establish a worldwide centralized antimalarial
      toxicity reporting system.

PMID- 22153749
TI  - Large eddy simulation of LDL surface concentration in a subject specific human
      aorta.
AB  - The development of atherosclerosis is correlated to the accumulation of lipids in
      the arterial wall, which, in turn, may be caused by the build-up of low-density
      lipoproteins (LDL) on the arterial surface. The goal of this study was to model
      blood flow within a subject specific human aorta, and to study how the LDL
      surface concentration changed during a cardiac cycle. With measured velocity
      profiles as boundary conditions, a scale-resolving technique (large eddy
      simulation, LES) was used to compute the pulsatile blood flow that was in the
      transitional regime. The relationship between wall shear stress (WSS) and LDL
      surface concentration was investigated, and it was found that the accumulation of
      LDL correlated well with WSS. In general, regions of low WSS corresponded to
      regions of increased LDL concentration and vice versa. The instantaneous LDL
      values changed significantly during a cardiac cycle; during systole the surface
      concentration was low due to increased convective fluid transport, while in
      diastole there was an increased accumulation of LDL on the surface. Therefore,
      the near-wall velocity was investigated at four representative locations, and it
      was concluded that in regions with disturbed flow the LDL concentration had
      significant temporal changes, indicating that LDL accumulation is sensitive to
      not only the WSS but also near-wall flow.

PMID- 22153750
TI  - Cardiovascular solid mechanics grows and remodels.

PMID- 22153751
TI  - The effects of short-term selenium stress on Polish and Finnish wheat seedlings
      EPR, enzymatic and fluorescence studies.
AB  - Biochemical analyses of antioxidant content were compared with measurements of
      fluorescence and electron paramagnetic resonance (EPR) to examine the alteration
      of radicals in wheat seedlings exposed to 2 days of selenium stress. Two
      genotypes of Polish and one of Finnish wheat, differing in their tolerance to
      long-term stress treatment, were cultured under hydroponic conditions to achieve
      the phase of 3-leave seedlings. Afterwards, selenium (sodium selenate, 100 MUM
      concentration) was added to the media. After Se-treatment, all varieties showed
      an increase in carbohydrates (soluble and starch), ascorbate and glutathione
      content in comparison to non-stressed plants. These changes were more visible in
      Finnish wheat. On the basis of lipid peroxidation measurements, Finnish wheat was
      recognized as the genotype more sensitive to short-term Se-stress than the Polish
      varieties. The antioxidant enzyme activities (superoxide dismutase, ascorbate
      peroxidase and glutathione reductase) increased in Polish genotypes, whereas they
      decreased in Finnish wheat plants cultured on Se media. The action of reactive
      oxygen species in short-term action of Se stress was confirmed by the reduction
      of PSII and PSI system activities (measured by fluorescence parameters and EPR,
      respectively). EPR studies showed changes in redox status (especially connected
      with Mn(II)/Mn(III), and semiquinone/quinone ratios) in wheat cell after Se
      treatment. The involvement of the carbohydrate molecules as electron traps in
      production of long-lived radicals is postulated.

PMID- 22153752
TI  - The changing nature of avian influenza A virus (H5N1).
AB  - Highly pathogenic avian influenza A virus subtype H5N1 has been endemic in some
      bird species since its emergence in 1996 and its ecology, genetics and antigenic
      properties have continued to evolve. This has allowed diverse virus strains to
      emerge in endemic areas with altered receptor specificity, including a new H5
      sublineage with enhanced binding affinity to the human-type receptor. The
      pandemic potential of H5N1 viruses is alarming and may be increasing. We review
      here the complex dynamics and changing nature of the H5N1 virus that may
      contribute to the emergence of pandemic strains.

PMID- 22153753
TI  - The pig: a model for human infectious diseases.
AB  - An animal model to study human infectious diseases should accurately reproduce
      the various aspects of disease. Domestic pigs (Sus scrofa domesticus) are closely
      related to humans in terms of anatomy, genetics and physiology, and represent an
      excellent animal model to study various microbial infectious diseases. Indeed,
      experiments in pigs are much more likely to be predictive of therapeutic
      treatments in humans than experiments in rodents. In this review, we highlight
      the numerous advantages of the pig model for infectious disease research and
      vaccine development and document a few examples of human microbial infectious
      diseases for which the use of pigs as animal models has contributed to the
      acquisition of new knowledge to improve both animal and human health.

PMID- 22153754
TI  - The significant immunological characteristics of peripheral blood neutrophil-to
      lymphocyte ratio and Fas ligand expression incidence in nephrectomized tumor in
      late recurrence from renal cell carcinoma.
AB  - OBJECTIVE: In order to characterize the significance of immune system function in
      patients with advanced renal cell carcinoma (RCC), we investigated the
      interactive relationships among the following parameters: metastatic
      characteristics, expression of Fas ligand (FasL) in nephrectomized specimens,
      immunological parameters, and patient's prognosis. MATERIALS AND METHODS: Thirty
      five patients with advanced RCC were stratified into 3 groups according to the
      characteristics of metastasis timing, at first presentation (mFP), within 5 years
      of nephrectomy (early-recurrence), after 5 years (late-recurrence). Immunological
      parameters [hemoglobin, lymphocyte count, neutrophil/lymphocyte ratio (NLR),
      serum albumin, Eastern Cooperative Oncology Group (ECOG) performance status (PS),
      and Charlson Comorbidity Index], FasL expression in RCC, and patient prognosis
      from occurrence of metastasis were compared among the groups. Thirty-five
      patients were also stratified into 2 groups according to FasL positivity and
      individual parameters. Patient's prognosis and the remaining immunological
      parameters were compared between groups. RESULTS: The NLRs of the late-recurrence
      group were significantly lower than those of the mFP (P = 0.0004) and early
      recurrence (P = 0.013) groups. The FasL mRNA positivity of the late-recurrence
      group was significantly lower than those of the mFP (P = 0.001) and early
      recurrence (P = 0.0277) groups. The prognosis of the late-recurrence group was
      significantly better than that of the early-recurrence group (P = 0.0255). NLRs
      were significantly lower in the FasL-negative group than in the -positive group
      (P = 0.0182). The cause-specific survival rates of the ECOG PS 0 group were
      significantly higher than that of the ECOG PS > 0 group (P < 0.0001).
      CONCLUSIONS: Our results suggest the associations of the prognosis in advanced
      RCC with peripheral blood NLR and FasL expression in nephrectomized tumor. The
      characteristics of lower values of NLR and FasL expression positivity in late
      recurrence compared with other metastatic timings suggest strong host immune
      activity, and may imply relatively long survival. On the other hand, elucidation
      of the patient's general condition obtained not only by chemical data but also by
      ECOG PS is crucial in the management of patients with advanced RCC.

PMID- 22153755
TI  - Consolidative surgery after targeted therapy for renal cell carcinoma.
AB  - Renal cell carcinoma is the most lethal of the common genitourinary neoplasms,
      with 30% to 40% of patients eventually dying from disease progression. Although
      the recent development of targeted therapies against kidney cancer has yielded
      substantially improved tumor response rates and progression-free survival, these
      agents are still not curative. The integration of systemic therapies with surgery
      still represents the best management for select patients with advanced disease.
      Specifically, consolidative surgery may play a vital role in the management of
      this challenging patient population. However, concerns remain regarding the
      potential for increased surgical morbidity complicating the integration of
      surgery after targeted therapy. Careful patient selection and specific
      precautions to increase surgical safety should be implemented. 

PMID- 22153757
TI  - Retinoid and lipid metabolism.

PMID- 22153756
TI  - The Personal Patient Profile-Prostate decision support for men with localized
      prostate cancer: a multi-center randomized trial.
AB  - OBJECTIVE: The purpose of this trial was to compare usual patient education plus
      the Internet-based Personal Patient Profile-Prostate, vs. usual education alone,
      on conflict associated with decision making, plus explore time-to-treatment, and
      treatment choice. METHODS: A randomized, multi-center clinical trial was
      conducted with measures at baseline, 1-, and 6 months. Men with newly diagnosed
      localized prostate cancer (CaP) who sought consultation at urology, radiation
      oncology, or multi-disciplinary clinics in 4 geographically-distinct American
      cities were recruited. Intervention group participants used the Personal Patient
      Profile-Prostate, a decision support system comprised of customized text and
      video coaching regarding potential outcomes, influential factors, and
      communication with care providers. The primary outcome, patient-reported
      decisional conflict, was evaluated over time using generalized estimating
      equations to fit generalized linear models. Additional outcomes, time-to
      treatment, treatment choice, and program acceptability/usefulness, were explored.
      RESULTS: A total of 494 eligible men were randomized (266 intervention; 228
      control). The intervention reduced adjusted decisional conflict over time
      compared with the control group, for the uncertainty score (estimate -3.61;
      (confidence interval, -7.01, 0.22), and values clarity (estimate -3.57;
      confidence interval (-5.85,-1.30). Borderline effect was seen for the total
      decisional conflict score (estimate -1.75; confidence interval (-3.61,0.11). Time
      to-treatment was comparable between groups, while undecided men in the
      intervention group chose brachytherapy more often than in the control group.
      Acceptability and usefulness were highly rated. CONCLUSION: The Personal Patient
      Profile-Prostate is the first intervention to significantly reduce decisional
      conflict in a multi-center trial of American men with newly diagnosed localized
      CaP. Our findings support efficacy of P3P for addressing decision uncertainty and
      facilitating patient selection of a CaP treatment that is consistent with the
      patient values and preferences.

PMID- 22153758
TI  - Sternoclavicular septic arthritis and empyema.

PMID- 22153759
TI  - Safety and efficacy of daptomycin for the treatment of hospitalized adult
      patients in Taiwan with severe staphylococcal infections.
AB  - BACKGROUND AND PURPOSE: The safety and efficacy of treating serious infections
      caused by Staphylococcus aureus with daptomycin in a Taiwanese population were
      studied. METHODS: A retrospective, multicenter study was performed in Taiwan
      between December 2007 and June 2009. This study included adult hospitalized
      patients who had received intravenous daptomycin therapy for infections caused by
      S aureus. All patients were followed until discharge from the hospital or death.
      RESULTS: A total of 52 patients (males, n=44; median age: 62 years) were
      evaluated. Infections included complicated skin and soft-tissue infections
      (n=14), catheter-related bacteremia (n=14), osteomyelitis and septic arthritis
      (n=12), endovascular infections and endocarditis (n=11), and urinary tract
      infections (n=1). Overall, 47 (90.4%) patients were successfully treated and
      their clinical symptoms were resolved. Adverse effects related to daptomycin were
      detected in nine patients, but none were required to discontinue daptomycin.
      CONCLUSION: The results support daptomycin as an effective and safe treatment for
      staphylococcal infections in Taiwanese populations.

PMID- 22153760
TI  - Leptospirosis with transient paraparesis and thrombocytopenia: a case report.
AB  - Leptospirosis is the most widespread zoonosis in the world. We present an unusual
      case of leptospirosis in a 44-year-old man with severe thrombocytopenia and
      transient paraparesis. The diagnosis of leptospirosis was confirmed by blood
      nested polymerase chain reaction, seroconversion of Leptospira IgM and the
      microscopic agglutination test. Nerve conduction studies were suggestive of early
      polyneuropathy involving the right peroneal nerve and bilateral sural nerves.
      Peripheral nerve palsy is a potential clinical feature of leptospirosis.

PMID- 22153762
TI  - Pneumonia due to pandemic (H1N1) 2009 influenza virus and Klebsiella pneumoniae
      capsular serotype K16 in a patient with nasopharyngeal cancer.
AB  - Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and group
      A Streptoccocus, but no Klebsiella pneumoniae were responsible for bacterial
      coinfections during the 2009 and previous influenza pandemics. We hereby report a
      case with concurrent bacteremic pneumonia due to an unusual capsular serotype K16
      K. pneumoniae and pandemic (H1N1) 2009 influenza in a patient with nasopharyngeal
      cancer. Such a coinfection has not previously been described.

PMID- 22153761
TI  - Successful treatment of septic shock and respiratory failure due to leptospirosis
      and scrub typhus coinfection with penicillin, levofloxacin, and activated protein
      C.
AB  - Leptospirosis and scrub typhus are common zoonoses and coinfection with both
      diseases has been reported sporadically, particularly in tropical and subtropical
      areas. A 53-year-old male presented with acute hypoxemic respiratory failure and
      septic shock due to leptospirosis and scrub typhus coinfection confirmed by
      serological assessments. Antibiotics, including intravenous penicillin and
      levofloxacin, were administered and human recombinant activated protein C was
      added because of a high risk of death due to septic shock with multiple organ
      failure. The patient's hemodynamics and hypoxemia substantially improved 4 days
      later and he had a complete recovery from the disease after 10 days of
      hospitalization. Coinfection of leptospirosis and scrub typhus may easily go
      unrecognized by physicians in febrile travelers or patients in the region where
      both diseases are endemic. In severe and critical cases of leptospirosis, scrub
      typhus, or coinfection with both, the use of APC in addition to appropriate
      antibiotic treatment and standard critical care might provide a greater chance
      for survival and a favorable outcome.

PMID- 22153763
TI  - Rapidly fatal community-acquired pneumonia due to Klebsiella pneumoniae
      complicated with acute myocarditis and accelerated idioventricular rhythm.
AB  - We describe a previously healthy 52-year-old man with rapidly fatal community
      acquired pneumonia caused by Klebsiella pneumoniae. The patient developed acute
      renal dysfunction, accelerated idioventricular rhythm (acute myocarditis), lactic
      acidosis and septic shock. He died within 15 hours after admission despite
      intravenous levofloxacin (750 mg daily) and aggressive medical treatment.

PMID- 22153764
TI  - Japanese viral encephalitis mimicking stroke with an initial manifestation of
      hemiplegia.
AB  - Japanese encephalitis (JE) is an endemic disease in Taiwan. After the program to
      vaccinate children against JE was implemented in 1968, the incidence of JE
      gradually started to decrease, but it is still an important infectious disease
      here. Neurological manifestations in JE vary highly during the initial stage of
      the disease. Focal neurological symptoms, such as hemiplegia, are rarely
      reported. A 46-year-old male with the initial presentation of abrupt hemiplegia
      and fever developed mental confusion after 1 day. No bacterial pathogen was
      isolated from the blood or cerebrospinal fluid (CSF). A diagnosis of JE was
      confirmed based on the presence of JE virus-specific immunoglobulin M in the CSF
      and serum samples. It is necessary to consider JE when a patient presents with
      abrupt hemiplegia with fever followed with mental confusion and seizure,
      especially if the patient comes from a JE-endemic area.

PMID- 22153765
TI  - Amino acid substitutions of quinolone resistance determining regions in GyrA and
      ParC associated with quinolone resistance in Acinetobacter baumannii and
      Acinetobacter genomic species 13TU.
AB  - BACKGROUND AND PURPOSE: Amino acid substitutions in GyrA and ParC are associated
      with resistance to quinolones in Acinetobacter baumannii (A baumannii), but this
      association is rarely elucidated in Acinetobacter genomic species (AGS) 13TU.
      This study aims to compare the association of amino acid substitutions in GyrA
      and ParC with quinolone resistance in A baumannii and AGS 13TU in Taiwan.
      METHODS: Eleven representative strains of A baumannii and 13 strains of AGS 13TU
      were selected from 402 bacteremic isolates. The sequences of quinolone resistance
      determining regions of gyrA and parC were determined. Minimal inhibitory
      concentrations (MICs) of nalidixic acid, ciprofloxacin, levofloxacin and
      moxifloxacin were determined by agar dilution method. RESULTS: Ser83Leu
      substitution in GyrA in A baumannii (one strain) was associated with resistance
      to all tested quinolones. This substitution plus a Ser80Leu or Ser80Tyr in ParC
      in A baumannii (four strains) and AGS 13TU (two strains) were associated with
      higher MICs of all quinolones. All but one quinolone MICs of A baumannii (one
      strain) and AGS 13TU (two strains) carrying a single substitution Ser56Asn in
      ParC remained in the susceptibility breakpoint. The Ser83Leu substitution in
      GyrA, even with additional Ser56Asn substitution in ParC, was associated with
      resistance to only nalidixic acid, but not other newer quinolones in AGS 13TU
      (two strains). CONCLUSION: A baumannii and AGS 13TU possessed similar quinolone
      resistance associated with amino acid substitutions in GyrA and ParC. Further
      study with more strains is needed to determine whether a single Ser83Leu
      substitution in GyrA was associated with a high level of quinolone MIC only in A
      baumannii, but not in AGS 13TU.

PMID- 22153766
TI  - Serum levels of dehydroepiandrosterone sulfate (DHEAS) in ocular toxoplasmosis.
AB  - There are no previous study about ocular toxoplasmosis and serum levels of
      dehydroepiandrosterone sulphated hormone (DHEAS). We use the chemoluminiscence
      automatized Immulite assay to determine the levels of DHEAS. Four groups were
      studied: (1) Individuals with chronic asymptomatic infection with a positive test
      for IgG anti-Toxoplasma and without ocular lesions (n = 16); (2) Chronic
      asymptomatic patients with retinal scars of retinochoroiditis by Toxoplasma (n =
      19); (3) Acute symptomatic patients with active retinochoroiditis by Toxoplasma
      (n = 26); (4) Individuals with negative assays for IgG anti-Toxoplasma (n = 21).
      Comparison of DHEAS levels between groups were adjusted by age and sex and non
      parametric Kruskall Wallis statistical tests were applied. No significant
      differences in serum levels of DHEAS were found between groups when age and sex
      were controlled. DHEAS levels were not significantly different in active ocular
      toxoplasmosis related to non active or non infected persons.

PMID- 22153767
TI  - [Biliary complications after liver transplant].
AB  - There have been biliary complications since the beginning of liver transplants,
      and is a topic of great interest due to its high incidence, as well as their
      influence on morbidity and mortality. The biliary fistula is currently uncommon
      and its management is straightforward. Anastomotic stenosis continues to have an
      incidence of 10-15%. Although the current treatment of choice is endoscopic
      retrograde cholangiopancreatography (ERCP), surgical treatment (hepatico
      jejunostomy) continues to have an important role. Non-anastomotic stenosis has an
      incidence of 5-10%, and is associated with ischaemic or immunological factors,
      and usually involves a re-transplant. Choledocholithiasis has an incidence of 5
      10%, with the treatment of choice being ERCP. However the treatment of biliary
      complications should be individualised. We must take into account, liver
      function, the general health status of the patient, and the availability and
      experience of the team in the different therapeutic options.

PMID- 22153768
TI  - Determinants of co-contraction during walking before and after arthroplasty for
      knee osteoarthritis.
AB  - BACKGROUND: Knee osteoarthritis patients co-contract in knee-related muscle pairs
      during walking. The determinants of this co-contraction remain insufficiently
      clear. METHODS: A heterogeneous group of 14 patients was measured before and one
      year after knee arthroplasty, and compared to 12 healthy peers and 15 young
      subjects, measured once. Participants walked on a treadmill at several imposed
      speeds. Bilateral activity of six muscles was registered electromyographically,
      and co-contraction time was calculated as percentage of stride cycle time. Local
      dynamic stability and variability of sagittal plane knee movements were
      determined. The surgeon's assessment of alignment was used. Pre-operatively,
      multivariate regressions on co-contraction time were used to identify
      determinants of co-contraction. Post-operatively it was assessed if predictor
      variables had changed in the same direction as co-contraction time. FINDINGS:
      Patients co-contracted longer than controls, but post-operatively, differences
      with the healthy peers were no longer significant. Varus alignment predicted co
      contraction time. No patient had post-operative varus alignment. The patients'
      unaffected legs were more unstable, and instability predicted co-contraction time
      in both legs. Post-operatively, stability normalised. Longer unaffected side co
      contraction time was associated with reduced affected side kinematic variability.
      Post-operatively, kinematic variability had further decreased. INTERPRETATIONS:
      Varus alignment and instability are determinants of co-contraction. The benefits
      of co-contraction in varus alignment require further study. Co-contraction
      probably increases local dynamic stability, which does not necessarily decrease
      the risk of falling. Unaffected side co-contraction contributed to decreasing
      affected side variability, but other mechanisms than co-contraction may also have
      played a role in decreasing variability.

PMID- 22153769
TI  - Influence of temporal pressure on anticipatory postural control of medio-lateral
      stability during rapid leg flexion.
AB  - During leg flexion from erect posture, postural stability along the medio-lateral
      direction is organized in advance during "anticipatory postural adjustments"
      (APAs). This study aimed to investigate the influence of temporal pressure on
      this anticipatory postural control of medio-lateral stability. Eight young
      healthy participants performed series of leg flexions (1) as soon as possible in
      response to an acoustic signal (reaction-time condition; condition with temporal
      pressure) and (2) in a self-initiated condition (no temporal pressure). Results
      showed that APAs duration was shorter in the reaction-time condition as compared
      to the self-initiated condition; this shortening was compensated by an increase
      in the medio-lateral center-of-pressure displacement so that the dynamic
      stability reached at foot-off, as measured by the "extrapolated center-of-mass",
      remained unchanged. It is concluded that when a complex task is performed under
      temporal pressure, the central nervous system is able to modulate the spatio
      temporal features of APAs in a way to both hasten the initiation of the voluntary
      movement and maintain optimal conditions of dynamic stability. In other words, it
      seems that the central nervous system does not "trade off optimal stability for
      speed of movement initiation under reaction-time condition", as it had been
      proposed in the literature.

PMID- 22153770
TI  - Cycling exercise with functional electrical stimulation improves postural control
      in stroke patients.
AB  - The aim of this study is to determine whether short term functional electrical
      stimulation (FES)-assisted cycling training can affect the postural control of
      stroke patients, and whether the application of FES can enhance the effect of
      cycling training. 20 stroke patients were randomly assigned to the FES-cycling
      group (FES-CG) or the cycling group (CG). Measurements were completed before and
      immediately after each 20 min training sessions. The measurements included a
      balance test (to quantify the postural control ability), a Hoffmann's
      reflex/motor response ratio (H/M ratio) test and a pendulum test (to quantify the
      muscle tone). In the balance test, some parameters in all directions exhibited
      significant intervention effects between the FES-CG group and the CG group. The
      H/M ratios (p=.014; .005, FES-CG and CG respectively) and relaxation index
      (p=.005; .047, FES-CG and CG respectively) revealed significant difference
      between FES-CG and CG group. The change ratios of directional control in the
      forward direction and H/M ratio revealed significant difference (p=.022; .015)
      between FES-CG and CG among subjects with higher muscle tone. The stroke
      subjects' postural control was improved while their muscle tone was reduced after
      the 20 min cycling training program both with and without FES. We conclude that
      cycling training, with or without FES may reduce spasticity in stroke patients.
      The application of FES in cycling exercise was shown to be more effective in
      stroke patients with higher muscle tone.

PMID- 22153771
TI  - Evaluating asymmetry in prosthetic gait with step-length asymmetry alone is
      flawed.
AB  - Prosthetic gait is often asymmetric in step length, but the direction of this
      asymmetry varies inconsistently across amputees. This situation is akin to that
      seen in stroke patients, where step-length asymmetry has been shown to be the
      additive result of asymmetries in trunk progression and asymmetries in forward
      foot placement relative to the trunk. The present study examined the validity of
      this notion in three trans-tibial and seven trans-femoral amputees wearing a
      unilateral prosthesis while walking over a walkway at a comfortable and slower
      than-comfortable speed. The latter manipulation was added to examine the
      expectation that the magnitude of the trunk-progression asymmetry - attributable
      to a weaker propulsion generating capacity on the prosthetic side - would be
      smaller when walking slower because of the diminished propulsion demands. Step
      length, forward foot placement relative to the trunk, and trunk progression of
      prosthetic and non-prosthetic steps, as well as asymmetries therein, were
      quantified. The direction of step-length and forward foot placement asymmetries
      varied inconsistently across (but consistently within) participants. As expected,
      step-length asymmetry depended on the combination of asymmetries in forward foot
      placement and trunk progression, with a smaller contribution of trunk-progression
      asymmetry at slow speed. These results extend our previous finding for hemiplegic
      patients that an analysis of gait asymmetry in terms of step length alone is
      flawed to prosthetic gait, implying that knowledge of asymmetries in trunk
      progression and forward foot placement relative to the trunk is required to help
      elucidate the contribution of underlying impairments (viz. propulsion generating
      capacity) and adopted compensations on prosthetic gait asymmetry.

PMID- 22153772
TI  - Protective effect of IgM against colonization of the respiratory tract by
      nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia.
AB  - BACKGROUND: Primary immunoglobulin deficiencies lead to recurrent bacterial
      infections of the respiratory tract and bronchiectasis, even with adequate
      immunoglobulin replacement therapy. It is not known whether patients able to
      secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to
      these infections as patients who lack IgM production (eg, those with
      panhypogammaglobulinemia [PHG]). OBJECTIVE: This study is aimed at identifying
      specific microbiological and clinical (infections) characteristics that
      distinguish immunoglobulin-substituted patients with PHG from patients with HIgM
      syndrome. METHODS: A cohort of patients with HIgM syndrome (n = 25) and a cohort
      of patients with PHG (n = 86) were monitored prospectively for 2 years while
      receiving similar polyvalent immunoglobulin replacement therapies. Regular
      bacterial analyses of nasal swabs and sputum were performed, and clinical events
      were recorded. In parallel, serum and saliva IgM antibody concentrations were
      measured. RESULTS: When compared with patients with PHG, patients with HIgM
      syndrome were found to have a significantly lower risk of nontypeable Haemophilus
      influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63).
      Moreover, patients with HIgM syndrome (including those unable to generate somatic
      hypermutations of immunoglobulin genes) displayed anti-nontypeable H influenzae
      IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a
      lower incidence of acute respiratory tract infections. CONCLUSIONS: IgM
      antibodies appear to be microbiologically and clinically protective and might
      thus attenuate the infectious consequences of a lack of production of other
      immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG
      replacement therapy might not fully compensate for IgM deficiency. It might thus
      be worth adapting long-term antimicrobial prophylactic regimens according to the
      underlying B-cell immunodeficiency phenotype.

PMID- 22153773
TI  - Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase
      deficient severe combined immune deficiency.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant skin tumor
      associated with a characteristic chromosomal translocation (t[17;22][q22;q13])
      resulting in the COL1A1-platelet-derived growth factor beta(PDGFB) fusion gene.
      This malignancy is rarely diagnosed in childhood. OBJECTIVE: We observed an
      unexpected high incidence of this DFSP in children affected with adenosine
      deaminase-deficient severe combined immunodeficiency (ADA-SCID) and set out to
      evaluate the association of these 2 clinical entities. METHODS: Twelve patients
      with ADA-SCID were evaluated with a complete dermatologic examination and skin
      biopsy when indicated. Conventional cytogenetic and molecular analyses
      (fluorescence in situ hybridization, RT-PCR, or both) were performed when
      possible. RESULTS: Eight patients were found to have DFSP. Six patients had
      multicentric involvement (4-15 lesions), primarily of the trunk and extremities.
      Most lesions presented as 2- to 15-mm, round atrophic plaques. Nodular lesions
      were present in 3 patients. In all cases CD34 expression was diffusely positive,
      and diagnosis was confirmed either by means of cytogenetic analysis, molecular
      testing, or both. The characteristic DFSP-associated translocation,
      t(17;22)(q22;q13), was identified in 6 patients; results of fluorescence in situ
      hybridization were positive for fusion of the COL1A1 and PDGFB loci in 7
      patients; and RT-PCR showed the COL1A1-PDGFB fusion transcript in 6 patients.
      CONCLUSIONS: We describe a previously unrecognized association between ADA-SCID
      and DFSP with unique features, such as multicentricity and occurrence in early
      age. We hypothesize that the t(17;22)(q22;q13) translocation that results in
      dermal overexpression of PDGFB and favors the development of fibrotic tumors
      might arise because of the known DNA repair defect in patients with ADA-SCID.
      Although the natural course of DFSP in the setting of ADA-SCID is unknown, this
      observation should prompt regular screening for DFSP in patients with ADA-SCID.

PMID- 22153774
TI  - Low diversity of the gut microbiota in infants with atopic eczema.
AB  - BACKGROUND: It is debated whether a low total diversity of the gut microbiota in
      early childhood is more important than an altered prevalence of particular
      bacterial species for the increasing incidence of allergic disease. The advent of
      powerful, cultivation-free molecular methods makes it possible to characterize
      the total microbiome down to the genus level in large cohorts. OBJECTIVE: We
      sought to assess microbial diversity and characterize the dominant bacteria in
      stool during the first year of life in relation to atopic eczema development.
      METHODS: Microbial diversity and composition were analyzed with barcoded 16S rDNA
      454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in
      20 infants with IgE-associated eczema and 20 infants without any allergic
      manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). RESULTS:
      Infants with IgE-associated eczema had a lower diversity of the total microbiota
      at 1 month (P = .004) and a lower diversity of the bacterial phylum Bacteroidetes
      and the genus Bacteroides at 1 month (P = .02 and P = .01) and the phylum
      Proteobacteria at 12 months of age (P = .02). The microbiota was less uniform at
      1 month than at 12 months of age, with a high interindividual variability. At 12
      months, when the microbiota had stabilized, Proteobacteria, comprising gram
      negative organisms, were more abundant in infants without allergic manifestation
      (Empirical Analysis of Digital Gene Expression in R [edgeR] test: P = .008, q =
      0.02). CONCLUSION: Low intestinal microbial diversity during the first month of
      life was associated with subsequent atopic eczema.

PMID- 22153775
TI  - Deletion of the long arm but not the 5q31 region of chromosome 5 in myeloid
      malignancies.

PMID- 22153777
TI  - Sleep duration and hypercholesterolaemia: Results from the National Health
      Interview Survey 2008.
AB  - BACKGROUND: Previous studies have shown an inconsistent association between sleep
      duration and hypercholesterolaemia. This study examined the association between
      sleep duration and hypercholesterolaemia in a nationally representative sample of
      US adults. METHODS: A cross-sectional study of 16,652 participants in the 2008
      National Health Interview Survey (aged ?18years, 52.5% women) was conducted.
      Sleep duration was categorized as ?5, 6, 7, 8, or ?9h. Hypercholesterolaemia
      (n=5578) was assessed by questionnaire. RESULTS: A significant gender difference
      was found in the association between sleep duration and hypercholesterolaemia (P
      interaction=0.003). Among women, sleep duration ?5h was positively associated
      with hypercholesterolaemia after adjusting for potential confounders and
      mediators including physical activity, psychological distress, body mass index,
      diabetes mellitus, and hypertension. Compared with a sleep duration of 7h
      (referent), the multivariate odds ratio (OR) of hypercholesterolaemia was 1.27
      (95% confidence interval [CI] 1.04-1.54) for sleep duration ?5h. In contrast,
      among men, sleep duration ?8h was inversely associated with
      hypercholesterolaemia. Compared with a sleep duration of 7h (referent), the
      multivariate OR of hypercholesterolaemia was 0.80 (95% CI 0.69-0.94) and 0.78
      (95% CI 0.60-1.00) for sleep durations of 8 and ?9h, respectively. In subgroup
      analyses, the positive association between sleep duration ?5h and
      hypercholesterolaemia in women, and the inverse association between sleep
      duration ?8h and hypercholesterolaemia in men, were more pronounced among those
      aged <60 years and race/ethnic groups other than non-Hispanic Whites. CONCLUSION:
      Sleep duration ?5h was positively associated with hypercholesterolaemia in women,
      whereas sleep duration ?8h was inversely associated with hypercholesterolaemia in
      men.

PMID- 22153778
TI  - A new classification for sleep analysis in critically ill patients.
AB  - BACKGROUND: Patients in intensive care units (ICUs) experience severe sleep
      alterations and conventional sleep scoring rules are difficult to use in these
      patients. In a previous study, we showed that abnormal sleep EEG and wake EEG
      patterns could predict the outcome of noninvasive ventilation in a group of
      patients treated for acute respiratory failure. Our aims were to assess the
      prevalence of these abnormal sleep/wake EEG patterns in a larger group and search
      for objective parameters to help their identification. METHODS: We reviewed sleep
      studies previously performed with full polysomnography during 17-h in conscious
      nonsedated ICU patients receiving invasive ventilation during weaning or
      noninvasive ventilation for acute respiratory failure. RESULTS: We included 57
      patients. Sleep scoring using conventional rules was not feasible in 16 (28%)
      patients due to the absence of stage-2 markers. Wake EEG in these 16 patients,
      although recognizable, showed abnormal features, including decreased reactivity
      to eye opening and slower peak EEG frequency compared to patients with normal
      sleep-wake EEGs. CONCLUSION: In almost one third of awake mechanically ventilated
      ICU patients, sleep cannot be classified with standard criteria. Two new states,
      atypical sleep and pathologic wakefulness, need to be added. We suggest rules for
      scoring these states. The origin and links with outcomes of these abnormal EEG
      patterns deserve investigation.

PMID- 22153779
TI  - The effect of zolpidem on sleep quality, stress status, and nondipping
      hypertension.
AB  - OBJECTIVE: Poor sleep quality and stress status have previously been shown to be
      closely associated with higher activation of the sympathetic nervous system and
      to be independent predictors of nondipping hypertension. This study aimed to
      evaluate the effects of the non-hypotensive sedative zolpidem on sleep quality,
      stress status, and nondipping hypertension. METHODS: A total of 103 nondippers
      were defined as poor or good sleepers by the Pittsburgh Sleep Quality Index. They
      were randomized to receive zolpidem or placebo treatment for 30 days. Stress
      status was assessed by the Perceived Stress Scale, and levels of epinephrine and
      norepinephrine were examined to investigate the underlying mechanisms. RESULTS:
      Poor sleepers treated with zolpidem for 30 days showed significant improvements
      in sleep quality and stress levels (P<0.01). More nondippers were converted to
      dippers in the group of poor sleepers treated with zolpidem (11 of 22 patients,
      50.0%) than in the placebo (2 of 23, 8.7%) (P<0.01). Epinephrine and
      norepinephrine levels were significantly reduced in poor sleepers treated with
      zolpidem (P<0.05). CONCLUSION: The results of this study suggest that zolpidem
      can improve sleep quality and stress status, and can convert nondippers with poor
      sleep quality into dippers. It may be an option for treating nondipping
      hypertensive patients with poor sleep quality.

PMID- 22153780
TI  - Prevalence and correlates of delayed sleep phase in high school students.
AB  - PURPOSE: To investigate prevalence and correlates of delayed sleep phase,
      characterized by problems falling asleep in the evening and rising at adequate
      times in the morning, in a large sample of Norwegian high school students.
      METHODS: A randomized sample of 1285 high school students (aged 16-19 years)
      participated in an internet based study answering questions about sleep habits,
      height, weight, smoking, alcohol use, school grades, and anxiety and depression
      symptoms. Delayed sleep phase was operationalized as difficulties falling asleep
      before 2 a.m. at least three nights per week together with much or very much
      difficulty waking up in the morning. RESULTS: The results show a prevalence of
      delayed sleep phase of 8.4%. In all, 68% of these students (5.7% of the total
      sample) also reported problems advancing their sleep period as well as one
      daytime consequence (oversleeping at least two days a week or experiencing
      much/very much sleepiness at school). Delayed sleep phase was associated with
      lower average school grades, smoking, alcohol usage, and elevated anxiety and
      depression scores. CONCLUSIONS: Delayed sleep phase appears to be common amongst
      Norwegian adolescents and is associated with negative outcomes such as lower
      average school grades, smoking, alcohol usage, and elevated anxiety and
      depression scores.

PMID- 22153781
TI  - The plight of nuns: hazards of nulliparity.

PMID- 22153782
TI  - [Listeria monocytogenes osteomyelitis].

PMID- 22153783
TI  - [The stroke care system in Terres de l'Ebre, Spain, after the implementation of
      the Stroke Code model: Ebrictus Study].
AB  - BACKGROUND AND OBJECTIVE: We aimed to know the characteristics of the urgent
      stroke assistance system, the Stroke Code (SC) model, 2 years after its
      implementation through testing the specific impact on several result indicators
      on individuals with a first stroke. PATIENTS AND METHOD: Prospective study of a
      cohort who suffered a first stroke episode, 15 to 89-year-old. Several clinical
      indicators were selected to evaluate results according to the SC and an analysis
      survival for Kaplan-Meier's curves was made as well as a bivariate analysis
      between dead and surviving patients. Data were collected by a community based
      registry. RESULTS: A total of 380 patients <=80-year-aged were enrolled and the
      SC was activated in 54.3% (CI95%: 49,0-59.3), 77% at the hospital. An 80% of the
      therapeutic window was wasted before arrival to hospital. In 13.9% (CI95%: 9,2
      19,8) thrombolysis was used. The immediate mortality was 9.9% (CI95%: 7.5-12.5).
      CONCLUSIONS: The implantation of the SC is a system that improved the welfare
      chain of stroke in the whole territory, but its activation in the area of primary
      care was low.

PMID- 22153784
TI  - A novel method of obtaining 3D images of detached retina.
AB  - We describe a new method of obtaining three-dimensional (3D) images of detached
      retina. Twelve-slice photos of the partial retina were obtained according to the
      twelve positions on a clock face. Twelve sections were then cut from these photos
      and joined together. Each sector was resized to match nearby sectors and the
      complete retinal picture was then created. A sphere mapping algorithm was used to
      map the two-dimensional (2D) picture to a sphere, which was then used to simulate
      the actual eyeball. Finally, a 3D image of the entire retina with a clearly
      visible detached section was created by the Visualization Toolkit (VTK).

PMID- 22153785
TI  - Performance of the frequency domain indices with respect to sleep staging.
AB  - OBJECTIVE: To compare computerized staging using spectral analyses of various
      electrophysiological signals with manual sleep staging. METHODS: Sleep recordings
      from 21 normal subjects were scored by an experienced rater and by a dichotomous
      algorithm. The performance of the spectral indices was assessed by the largest
      kappa value (LKV). RESULTS: Theta/beta power ratio of the electroencephalogram,
      high frequency power (8-58 Hz) of the electromyogram (PEMG), mean R-R interval,
      and total power (0-16 Hz) of the body acceleration (PACCE) had high (>0.5) LKVs
      when differentiating between waking and sleep. To differentiate sleep with (stage
      2 and slow wave sleep) and without (rapid eye movement and stage 1 sleep)
      spindles, sigma/beta power ratio had high LKVs. PEMG had a medium (>0.25) LKV to
      separate rapid eye movement from stage 1 sleep whereas delta/beta power ratio had
      a high LKV to separate stage 2 and slow wave sleep. CONCLUSION: The frequency
      components of electroencephalogram perform well in identifying sleep, sleep with
      spindles, and slow wave sleep. Electromyogram, heart rate, and body acceleration
      offer high agreement only when differentiating between wakefulness and sleep.
      SIGNIFICANCE: The human-machine agreement is acceptable with spectral parameters,
      but heart rate and body acceleration still cannot substitute for
      electroencephalogram.

PMID- 22153786
TI  - Imaging trait anxiety in high anxiety F344 rats: Focus on the dorsomedial
      prefrontal cortex.
AB  - Functional magnetic resonance imaging (fMRI) has become an important method in
      clinical psychiatry research whereas there are still only few comparable
      preclinical investigations. Herein, we report that fMRI in rats can provide key
      information regarding brain areas underlying anxiety behavior. Perfusion as
      surrogate for neuronal activity was measured by means of arterial spin labeling
      based fMRI in various brain areas of high anxiety F344 rats and control Sprague
      Dawley rats. In one of these areas, the dorsomedial prefrontal cortex (dmPFC), c
      Fos labeling was compared between these two strains with immunolabeling. The
      effects of a neurotoxic ibotenic acid lesion of the dmPFC in F344 rats were
      examined in a social approach-avoidance anxiety procedure and fMRI. Regional
      brain activity of high anxiety F344 rats was different in selective cortical and
      subcortical areas as compared to that of low anxiety Sprague-Dawley rats; the
      largest difference (i.e. hyperactivity) was measured in the dmPFC. Independently,
      c-Fos labeling confirmed that F344 rats show increased dmPFC activity. The
      functional role was confirmed by neurotoxic lesion of the dmPFC that reversed the
      high anxiety-like behavior and partially normalized the brain activity pattern of
      F344 rats. The current findings may have translational value as increased
      activity is reported in an equivalent cortical area in patients with social
      anxiety, suggesting that pharmacological or functional inhibition of activity in
      this brain area should be explored to alleviate social anxiety in patients.

PMID- 22153787
TI  - The efficacy of trimethoprim in wound healing of patients with epidermolysis
      bullosa: a feasibility trial.
AB  - BACKGROUND: There are no systemic therapies known to facilitate wound healing in
      patients with recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVES: We
      sought to assess the feasibility of a trial to examine the efficacy of
      trimethoprim (TMP) in healing chronic wounds in patients with RDEB and to examine
      the effect of TMP on lesion counts, quality of life, and emergence of antibiotic
      resistance. METHODS: We conducted a feasibility study using a prospective,
      randomized, double-blinded, placebo-controlled, crossover design. The study took
      place between October 2006 and September 2007 in the epidermolysis bullosa clinic
      at the Hospital for Sick Children in Toronto, Ontario, Canada. Liquid TMP or
      placebo was given orally or via gastrostomy tube in two divided doses for 2
      months; the main outcome measure was a decrease in surface area of selected
      chronic wounds. RESULTS: Ten subjects with RDEB were enrolled in the study; 7
      completed both study arms (4 male, 3 female). Age at enrollment was 14 +/- 5.4
      years. Although all patients showed improved wound healing on TMP, the crossover
      analysis, TMP versus placebo, approached but did not reach statistical
      significance (P = .08). While receiving TMP, 6 of 7 patients had more than 50%
      reduction in chronic wound surface area; while receiving placebo, 2 of 6 patients
      had more than 50% reduction in wound surface area (P = .03). Secondary outcome
      measures did not achieve statistical significance. LIMITATIONS: Small sample size
      is a limitation. CONCLUSIONS: This proof-of-concept study demonstrates the
      potential efficacy of TMP in improving wound healing in RDEB, and provides useful
      information for further prospective studies.

PMID- 22153788
TI  - Developmental potential of embryos from intracytoplasmic sperm injection cycles
      containing fragmented oocytes.
AB  - OBJECTIVE: To determine the incidence of fragmented oocytes in intracytoplasmic
      sperm injection (ICSI) cycles, describe the developmental potential of their
      sibling oocytes, and define clinical outcomes from affected cycles. DESIGN: Case
      control study. SETTING: Academic medical center. PATIENT(S): All ICSI cycles from
      January 2006 to December 2010 (n = 2,844) were reviewed for the presence of
      fragmented oocytes at cumulus stripping or fertilization check (n = 93). Sibling
      oocytes and corresponding embryos from index cycles were compared with matched
      control cycles without fragmented oocytes. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Cycle characteristics, embryo quality, and pregnancy rates per
      retrieval. RESULT(S): The incidence of ICSI cycles containing at least one
      fragmented oocyte was 3.3% (93/2,844). Twelve patients were represented more than
      once in these 93 index cycles. Only the first cycles (n = 81) were included, of
      which 28 contained fragmented oocytes at cumulus stripping, 48 at fertilization
      check, and five at both. Compared with matched controls, index cycles had fewer
      good-quality embryos available for transfer (18.8% vs. 32.1%) and significantly
      lower rates of implantation (20.3% vs. 32.7%), clinical pregnancy (33.3% vs.
      58.0%), and ongoing delivery (29.6% vs. 49.4%). The cumulative ongoing delivered
      rate was also significantly lower for index cycles (32.1% vs. 55.6%), with no
      difference in the percentage of cycles with cryopreserved embryos remaining at
      study conclusion (13.5% vs. 23.5%). CONCLUSION(S): Cohorts containing fragmented
      oocytes have decreased developmental potential. The biologic mechanisms
      underlying this occurrence merit further investigation, and patient counseling
      should reflect the possible decreased success rates associated with this aberrant
      developmental pattern.

PMID- 22153789
TI  - Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the
      Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in
      females, with a high prevalence. The etiology of this heterogeneous condition
      remains obscure, and its phenotype expression varies. Two widely cited previous
      ESHRE/ASRM sponsored PCOS consensus workshops focused on diagnosis (published in
      2004) and infertility management (published in 2008), respectively. The present
      third PCOS consensus report summarizes current knowledge and identifies knowledge
      gaps regarding various women's health aspects of PCOS. Relevant topics addressed
      all dealt with in a systematic fashion-include adolescence, hirsutism and acne,
      contraception, menstrual cycle abnormalities, quality of life, ethnicity,
      pregnancy complications, long-term metabolic and cardiovascular health, and
      finally cancer risk. Additional, comprehensive background information is provided
      separately in an extended online publication.

PMID- 22153790
TI  - Vulvo-cervico-vaginal manifestations and evaluation of Papanicolaou smears in
      pemphigus vulgaris and pemphigus foliaceus.
AB  - BACKGROUND: Vulvo-cervico-vaginal involvement has rarely been reported in
      pemphigus vulgaris (PV) and has not been reported in pemphigus foliaceus (PF).
      OBJECTIVES: We sought to evaluate genital lesions and Papanicolaou (Pap) smears
      in female patients with PV and PF. METHODS: This prospective study includes all
      consecutive cases of female patients with PV and PF seen from May 2009 to
      February 2010. Gynecologic examination was performed and Pap smears were
      collected for cytologic analysis from each patient. RESULTS: A total of 56
      patients were given a diagnosis of pemphigus (41 PV and 15 PF). Genital
      involvement was observed in 9 patients with PV (22%) and the vulva was the most
      common genital site of involvement. Of these 9 patients, 8 presented with active
      skin/mucous lesions. Four of 15 patients with PF had genital lesions and vulva
      was the exclusive site of involvement. Three of 4 patients with PF and genital
      involvement also showed active cutaneous lesions. Six of 56 patients (5 PV and 1
      PF) presented with atypical squamous cells of undetermined significance in Pap
      smear analysis. Upon further pathologic review, acantholytic cells were seen,
      confirming the diagnosis of pemphigus. LIMITATIONS: A small number of PF cases
      were studied. CONCLUSIONS: Vulvar lesions were the second most frequent site of
      mucous membrane PV. Herein we report the first case to our knowledge of
      symptomatic genital lesions in a patient with PF. Moreover, acantholytic cells in
      Pap smears were found in a patient with PF who was in complete remission off
      therapy with no clinical genital lesions and no circulating anti-desmoglein-1 and
      anti-desmoglein-3 autoantibodies. Gynecologic evaluation in patients with
      pemphigus, including a careful evaluation of Pap smears, should be recommended.

PMID- 22153791
TI  - Increased diagnosis of thin superficial spreading melanomas: A 20-year study.
AB  - BACKGROUND: Diagnostic practice by dermatopathologists evaluating pigmented
      lesions may have evolved over time. OBJECTIVES: We sought to investigate
      diagnostic drift among a group of dermatopathologists asked to re-evaluate cases
      initially diagnosed 20 years ago. METHODS: Twenty nine cases of dysplastic nevi
      with severe atypia and 11 cases of thin radial growth-phase melanoma from 1988
      through 1990 were retrieved from the pathology files of the Massachusetts General
      Hospital. All dermatopathologists who had rendered an original diagnosis for any
      of the 40 slides and the current faculty in the Massachusetts General Hospital
      Dermatopathology Unit were invited to evaluate the slide set in 2008 through
      2009. RESULTS: The mean number of melanoma diagnoses by the 9 study participants
      was 18, an increase from the original 11 melanoma diagnoses. A majority agreed
      with the original diagnosis of melanoma in all 11 cases. In contrast, a majority
      of current raters diagnosed melanoma in 4 of the 29 cases originally reported as
      dysplastic nevus with severe atypia. Interrater agreement over time was excellent
      (kappa 0.88) and fair (kappa 0.47) for cases originally diagnosed as melanoma and
      severely atypical dysplastic nevus, respectively. LIMITATIONS: The unbalanced
      composition of the slide set, lack of access to clinical or demographic
      information, access to only one diagnostic slide, and imposed dichotomous
      categorization of tumors were limitations. CONCLUSIONS: A selected cohort of
      dermatopathologists demonstrated a general trend toward the reclassification of
      prior nonmalignant diagnoses of severely atypical dysplastic nevi as malignant
      but did not tend to revise prior diagnoses of cutaneous melanoma as benign.

PMID- 22153792
TI  - The efficacy and safety of infliximab in patients with plaque psoriasis who had
      an inadequate response to etanercept: results of a prospective, multicenter, open
      label study.
AB  - BACKGROUND: In patients with psoriasis and inadequate response (IR) to tumor
      necrosis factor-alpha antagonist treatment, the incremental benefit of switching
      to another tumor necrosis factor-alpha antagonist is unknown. OBJECTIVE: We
      sought to evaluate the clinical response to an etanercept-to-infliximab switch in
      patients with psoriasis and IR to etanercept. METHODS: Adults with moderate-to
      severe plaque psoriasis and IR to etanercept (>= 4 months) were eligible for this
      open-label study (called PSUNRISE). Patients had a Physician Global Assessment
      (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or
      without concomitant oral systemic methotrexate or cyclosporine at baseline and
      during the study. Patients received intravenous infusions of infliximab 5 mg/kg
      at weeks 0, 2, 6, 14, and 22. PGA was used to evaluate efficacy at week 10
      (primary end point) and week 26 (durability). Safety was evaluated through the
      end of the study. RESULTS: Of 215 patients, only 10 received concomitant
      immunomodulators. At week 10, 65.4% of patients (138 of 211; 95% confidence
      interval 58.6%-71.8%) achieved a PGA score of clear (0) or minimal (1) (primary
      end point). This response was durable through week 26, at which time 61.3% (122
      of 199; 95% confidence interval 54.2%-68.1%) achieved a PGA score of clear (0) or
      minimal (1). There were no unexpected side effects or safety concerns.
      LIMITATIONS: This was an open-label, 26-week study; an incremental change of 1
      PGA point, even mild to minimal, was considered clinically significant, as most
      psoriasis practitioners seek to achieve minimal psoriasis or clear skin.
      CONCLUSION: After switching to infliximab, a substantial proportion of patients
      with psoriasis and IR to etanercept experienced rapid and durable improvement.

PMID- 22153793
TI  - Indoor tanning and risk of early-onset basal cell carcinoma.
AB  - BACKGROUND: Despite an increase in incidence of basal cell carcinoma (BCC) among
      young people and the ubiquity of indoor tanning in this population, few
      epidemiologic studies have investigated this exposure-disease relationship.
      OBJECTIVE: We sought to evaluate the association between indoor tanning and early
      onset BCC. METHODS: Patients with BCC (n = 376) and control subjects with minor
      benign skin conditions (n = 390) who were younger than 40 years of age were
      identified through Yale Dermatopathology. Participants provided information on
      ever indoor tanning, age of initiation, frequency, duration, burns while tanning,
      and type of tanning device during an in-person interview. We calculated odds
      ratios (OR) and 95% confidence intervals (CI) using multivariate logistic
      regression with never indoor tanners as the referent group. RESULTS: Ever indoor
      tanning was associated with a 69% increased risk of early-onset BCC (95% CI 1.15
      2.48). This association was stronger among females (OR 2.14, 95% CI 1.31-3.47),
      for multiple BCCs (OR 2.16, 95% CI 1.26-3.70), and for BCCs on the trunk and
      extremities (OR 2.81, 95% CI 1.57-5.02). Risk increased dose dependently with
      years using regular indoor tanning devices (P trend = .003), number of overall
      burns (P trend < .001), and burns to biopsy site (P trend < .001) from indoor
      tanning. Approximately one quarter (27%) of early-onset BCCs (or 43% among women)
      could be prevented if individuals never tanned indoors. LIMITATIONS: Potential
      recall bias of indoor tanning by patients and generalizability of the control
      population suggest replication in other studies is warranted. CONCLUSIONS: Indoor
      tanning was a strong risk factor for early-onset BCC, particularly among females.
      Indoor tanning should continue to be targeted by both policy-based and behavioral
      interventions, as the impact on BCC-associated morbidity may be substantial.

PMID- 22153795
TI  - A three-dimensional MRI study of variations in central sulcus location in 40
      normal subjects.
AB  - We used a computational strategy, in vivo morphometry, to evaluate structural
      magnetic resonance (MR) images to investigate individual variations in the
      location of the central sulcus (CS). To locate the CS we identified six key
      points on individual brain images obtained from 40 normal subjects and measured
      the distances between these points along the brain circumference. We also
      analyzed the difference between the actual location of the CS and the location
      predicted by conventional estimation methods. Individual variation exceeded 2.7
      cm for all measurements used to identify the location of the CS. The margin of
      error was approximately 2.7 cm even when the location of the CS was predicted by
      reported and commonly used methods. A "1 inch error" should be taken into
      consideration when the prediction relies solely on head circumference and surface
      measurements. Our results point to the importance of pre-surgical planning using
      individual brain images for each patient.

PMID- 22153794
TI  - Correlation of low SLC22A18 expression with poor prognosis in patients with
      glioma.
AB  - We investigated the expression of the putative tumor suppressor SLC22A18 to
      evaluate it as a prognostic marker in glioma patients. Immunohistochemical and
      Western blot analyses of clinical tissue samples obtained from 120 patients with
      glioma were performed. Low expression of SLC22A18 was observed in 71.7% of
      patients. Loss of SLC22A18 expression in glioma was significantly related to
      pathological grade (p = 0.003). High pathological grade (World Health
      Organization III-IV) was correlated with negative (low or absent) expression of
      SLC22A18, which was correlated with a significantly shorter overall patient
      survival than in those with positive (high) expression (p = 0.007). Multivariate
      Cox regression analysis indicated that SLC22A18 expression level is an
      independent survival prognostic factor for patients with glioma (p = 0.011).
      Western blotting analysis confirmed decreased expression of SLC22A18 in glioma
      tissues compared with adjacent brain tissues. This study suggests that SLC22A18
      functions as a tumor suppressor in glioma and represents a candidate biomarker
      for long-term survival in this disease.

PMID- 22153797
TI  - Patrikios syndrome in two patients with treatable flail-leg weakness.
AB  - Flail-leg syndrome or lower limb diplegia is a form of motor neuron disease
      characterized by a slower progression rate. The differential diagnosis with motor
      neuropathy is important. We present two patients with a previous diagnosis of
      amyotrophic lateral sclerosis (ALS)-flail-leg syndrome, in whom
      neurophysiological studies suggested proximal conduction block. Both patients
      responded to immunomodulatory therapy, which suggested an immunologically
      mediated, treatable flail-leg syndrome phenotype. We stress the importance of
      fasciculations in the diagnosis of ALS, and the study of nerve root conduction in
      the differential diagnosis.

PMID- 22153796
TI  - Thyroid stimulating hormone microadenoma as a rare cause of thyrotoxicosis
      amenable to surgical cure.
AB  - Hyperthyroidism due to a thyroid stimulating hormone (TSH) pituitary adenoma is
      rare. We report a 29-year-old woman with thyrotoxicosis and elevated serum
      3,5,3',5'-tetraiodothyronine and TSH levels that resolved after a transsphenoidal
      excision of the detected TSH pituitary adenoma. The diagnosis and management
      options in such patients are reviewed.

PMID- 22153798
TI  - Overexpression of the Notch3 receptor in non-functioning pituitary tumours.
AB  - Human non-functioning pituitary adenomas cause hypopituitarism or the compression
      of adjacent structures. At present, there is no available medical treatment for
      these tumours. The Notch3 pathway has an important role in the progression of non
      functioning pituitary adenomas. We found, using reverse transcriptase-polymerase
      chain reaction, that Notch3 mRNA was significantly upregulated in clinically non
      functioning pituitary adenomas, and, using Western blotting, that Notch3 protein
      was expressed at a higher level in non-functioning pituitary adenomas than in
      normal human pituitary tissue. In addition, using immunohistochemistry, we
      observed that Notch3 is highly expressed in the cytoplasm of adenoma cells
      compared to normal pituitary cells. These results suggest that the overexpression
      of Notch3 mRNA and protein by non-functioning pituitary adenomas may facilitate
      the growth of these tumours. Our results provide the first comprehensive analysis
      of Notch3 mRNA and protein overexpression in non-functioning pituitary tumours.
      This study provides new insights into the pathogenesis of human non-functioning
      pituitary adenomas and implicates the Notch3 pathway as a molecular therapeutic
      target for their treatment.

PMID- 22153799
TI  - A novel haemodynamic cerebral aneurysm model of rats with normal blood pressure.
AB  - Cerebral aneurysms of traditional animal models are usually too small to be
      imaged in vivo. A novel rat model induced by ligation of the unilateral common
      carotid artery and contralateral pterygopalatine and external carotid arteries
      was investigated. To evaluate the morphological changes of the cerebral arteries,
      synchrotron radiation angiography was utilised at 1 month, 2 months and 3 months
      after induction. Cerebral aneurysms and expansion of anterior cerebral arteries
      in these rats were identified when the animals were alive. This novel model is
      useful for cerebral aneurysm research.

PMID- 22153800
TI  - An overview of concussion in sport.
AB  - Concussion is a sudden-onset, transient alteration of consciousness due to a
      combination of functional and structural brain disturbances following a physical
      impact transmitted to the brain. It is a common, although likely underreported,
      condition encountered in a wide range of sports. In the Australian Football
      League, concussion is estimated to occur at a rate of approximately seven
      injuries per team per season. While many instances of concussion are clinically
      mild, there is emerging evidence that a player's full recovery from a concussive
      injury may be more delayed and the sequelae of repeated concussions more severe
      than previously thought. In this light, a more conservative and rigorous approach
      to managing players with concussive injuries may be warranted, with the guiding
      principle being the player's immediate and long-term welfare. The current paper
      reviews the sports concussion literature. The definition, epidemiology,
      aetiology, pathophysiology, structural pathology, clinical features, assessment
      and investigation, treatment principles, and short-term and potential long-term
      complications of concussion are discussed. Special considerations in paediatric
      sports concussion, and the return-to-play implications of immediate, evolving and
      repetitive brain injury are also considered, as are the emerging concept and
      possible implications of subconcussive injury.

PMID- 22153801
TI  - Intrarenal metabolomics reveals the association of local organic toxins with the
      progression of diabetic kidney disease.
AB  - The pathological development of diabetic kidney disease (DKD) might involve
      metabolic perturbations in kidney tissue. The present study was designed to
      detect the systematic alterations of renal cortex metabolites thereby exploring
      the related mechanisms of DKD development and fosinopril treatment. Based on
      combined gas chromatography/time-of-flight mass spectrometry (GC-TOF MS) and
      liquid chromatography/time-of-flight mass spectrometry (UPLC-TOF MS) data
      acquiring platform, we have performed a metabolomic analysis of perfused renal
      cortex samples from the diabetic rats induced by streptozocin and treated with or
      without fosinopril, a pharmacological inhibitor of angiotensin II converting
      enzyme (ACEI). We identified a number of abnormal metabolites in the diabetic
      kidney, including groups of amino acids, carbohydrates, polyols, lyso
      phospholipids, glucuronides and other unidentified metabolites. Of them, an
      increase in intrarenal organic toxins including uremic toxins, glucuronides and
      glucotocixity-associated metabolites are highly correlated with diabetic kidney
      injury including 24h urinary protein levels and tubulointerstitial injury index.
      Treatment with fosinopril significantly attenuated diabetic kidney injury, and
      simultaneously blocked the intrarenal accumulation of these organic toxins,
      especially hippurate and glucuronides. These results indicate that intrarenal
      accumulation of organic toxins may be significant for the development of DKD and
      the related mechanisms deserve to be further investigated.

PMID- 22153802
TI  - Self-body recognition depends on implicit and explicit self-esteem.
AB  - The present contribution bridges research on body image, self-esteem, and body
      recognition. Recent work in neuroscience indicates a superiority in the
      processing of self relative to others' body parts. The present contribution shows
      that this ability is not universal but it is qualified by individual differences
      in implicit and explicit self-esteem. In fact, two studies (n1 = 41 and n2 = 35)
      using two different paradigms in body recognition and direct and indirect
      measures of self-esteem reveal that this advantage in recognizing one's own body
      parts is associated with one's level of self-esteem. Moreover, it appears that
      measures of implicit and explicit self-esteem provide different contributions to
      self-body recognition abilities and that these contributions depend on how self
      body recognition is assessed. Implications of these results are discussed notably
      in the perspective of research on body image.

PMID- 22153803
TI  - Translating ideas into action: two new features initiated by Translational
      Research, as genomics enters the clinics.

PMID- 22153805
TI  - Does the fat cell have something to say to the platelet about keeping thrombosis
      in check in diabetes?

PMID- 22153804
TI  - Quality of life and psychosocial factors in African Americans with hypertensive
      chronic kidney disease.
AB  - Health-related quality of life (HRQOL) is poorly understood in patients with
      chronic kidney disease (CKD) prior to end-stage renal disease. The association
      between psychosocial measures and HRQOL has not been fully explored in CKD,
      especially in African Americans. We performed a cross-sectional analysis of HRQOL
      and its association with sociodemographic and psychosocial factors in African
      Americans with hypertensive CKD. There were 639 participants in the African
      American Study of Kidney Disease and Hypertension Cohort Study. The Short Form-36
      was used to measure HRQOL. The Diener Satisfaction with Life Scale measured life
      satisfaction, the Beck Depression Inventory-II assessed depression, the Coping
      Skills Inventory-Short Form measured coping, and the Interpersonal Support
      Evaluation List-16 was used to measure social support. The mean participant age
      was 60 years at enrollment, and men comprised 61% of participants. Forty-two
      percent reported a household income less than $15,000/year. Higher levels of
      social support, coping skills, and life satisfaction were associated with higher
      HRQOL, whereas unemployment and depression were associated with lower HRQOL (P <
      0.05). A significant positive association between higher estimated glomerular
      filtration rate (eGFR) was observed with the Physical Health Composite (PHC)
      score (P = 0.004) but not in the Mental Health Composite (MHC) score (P = 0.24).
      Unemployment was associated with lower HRQOL, and lower eGFR was associated with
      lower PHC. African Americans with hypertensive CKD with better social support and
      coping skills had higher HRQOL. This study demonstrates an association between
      CKD and low HRQOL, and it highlights the need for longitudinal studies to examine
      this association in the future.

PMID- 22153806
TI  - Spontaneous platelet aggregation evaluated by laser light scatter in patients
      with type 2 diabetes: effects of short-term improved glycemic control and
      adiponectin.
AB  - Spontaneous platelet aggregation (SPA) is enhanced in patients with type 2
      diabetes. Adiponectin may inhibit platelet aggregation. The aims of the current
      study were to identify factors associated with in vitro SPA measured by a laser
      light scattering method and to investigate the effects of short-term glycemic
      control and adiponectin on SPA. In study 1, we investigated platelet aggregation
      in 20 healthy control subjects and 82 patients with type 2 diabetes. In study 2,
      we evaluated the changes of SPA and serum high-molecular-weight (HMW) adiponectin
      after 2 weeks of improved glycemic control in 20 hospitalized diabetic patients.
      In study 3, using washed platelets from 10 healthy subjects, in vitro SPA was
      measured over 15 min in the absence or presence of recombinant adiponectin (20
      MUg/mL). Platelet aggregation was assessed with a laser light scatter
      aggregometer that measured the size of platelet aggregates. SPA was defined as
      formation of small aggregates under constant stirring in the absence of any
      agonists. The area under the curve was calculated for SPA and also for agonist
      induced small, medium, and large aggregates. SPA was increased in diabetic
      patients compared with control subjects. In diabetic patients, SPA was correlated
      positively with plasma fibrinogen, fasting plasma glucose, glycated albumin, and
      high-sensitivity C-reactive protein. A stepwise multivariate analysis showed that
      plasma fibrinogen was the strongest independent determinant of SPA in diabetic
      patients. In 20 diabetic patients, SPA decreased significantly after 2 weeks of
      glycemic control. A significant negative correlation was found between changes of
      SPA and those of HMW adiponectin during treatment. The in vitro study showed that
      adiponectin inhibited the spontaneous aggregation of washed platelets. In
      conclusion, hyperfibrinogenemia and hyperglycemia are associated independently
      with SPA in patients with type 2 diabetes. SPA is reduced after even short-term
      improvement of glycemic control and adiponectin also inhibits SPA directly.

PMID- 22153807
TI  - Serum level of soluble CD26/dipeptidyl peptidase-4 (DPP-4) predicts the response
      to sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes controlled
      inadequately by metformin and/or sulfonylurea.
AB  - Dipeptidyl peptidase 4 (DPP-4) inhibitors is a new class of antihyperglycemic
      agents that is now available for the treatment of type 2 diabetes. We
      investigated the relationship between the baseline serum level of soluble CD
      26/DPP-4 and the response to treatment with sitagliptin, a DPP-4 inhibitor, over
      24 weeks in patients who had type 2 diabetes inadequately controlled by metformin
      and/or sulfonylurea therapy. We studied 52 consecutive patients with type 2
      diabetes who had poor glycemic control despite treatment with metformin and/or
      sulfonylurea. All patients were given 50 mg/day of sitagliptin and were followed
      at monthly intervals for 24 weeks. Treatment with sitagliptin decreased
      significantly hemoglobin A1c (HbA1c) from 7.91 +/- 1.08% at baseline to 6.96 +/-
      1.18% at 8 weeks, 7.04 +/- 0.77% at 16 weeks, and 7.08 +/- 0.80% at 24 weeks. The
      baseline serum level of sCD26 was correlated positively with HbA1c at both 16
      weeks and 24 weeks. Furthermore, the serum sCD26 level at baseline was also
      correlated positively with the changes from baseline of HbA1c at 16 and 24 weeks
      (r = 0.318, P = 0.0296 and r = 0.516, P = 0.0003, respectively). In a
      multivariate logistic regression model that explained 56.1% (R(2) = 0.561) of the
      variation of the changes from baseline of HbA1c at 24 weeks, the baseline HbA1c
      (beta = -0.638, P < 0.001) and serum sCD26 (beta = 0.357, P = 0.041) were
      independent determinants of the change of HbA1c at 24 weeks. In conclusions, a
      higher serum level of sCD26 is associated with a worse response to sitagliptin in
      patients with type 2 diabetes controlled inadequately by metformin and/or
      sulfonylurea therapy.

PMID- 22153808
TI  - Local control of experimental malignant pancreatic tumors by treatment with a
      combination of chemotherapy and intratumoral 224radium-loaded wires releasing
      alpha-emitting atoms.
AB  - We developed (224)Ra-loaded wires that when inserted into solid tumors, release
      radioactive atoms that spread in the tumor and irradiate it effectively with
      alpha particles (diffusing alpha-emitters radiation therapy [DaRT]). In this
      study, we tested the ability of intratumoral (224)Ra-loaded wires to control the
      local growth of pancreatic tumors and the enhancement of this effect by
      chemotherapy. Pancreatic mouse tumors (Panc02) were treated with (224)Ra-loaded
      wire(s) with or without gemcitabine. The tumor size and survival were monitored,
      and autoradiography was performed to evaluate the spread of radioactive atoms
      inside the tumor. Mouse and human pancreatic cancer cells, irradiated in vitro by
      alpha particles with or without chemotherapy, were evaluated for cell growth
      inhibition. The insertion of (224)Ra-loaded wires into pancreatic tumors in
      combination with gemcitabine achieved significant local control and was superior
      to each treatment alone. A dosimetric analysis showed the spread of radioactive
      atoms in the tumor around the wires. Alpha particles combined with gemcitabine or
      5-FU killed mouse and human cells in vitro better than each treatment alone. DaRT
      in combination with gemcitabine was proven effective against pancreatic tumors in
      vivo and in vitro, and the process may be applicable as a palliative treatment
      for patients with pancreatic cancer.

PMID- 22153809
TI  - Association of hypoxia inducible factor-1alpha polymorphisms with susceptibility
      to non-small-cell lung cancer.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a key regulator of cellular
      response to hypoxia and has been suggested to play an important role in
      tumorigenesis and metastasis. The aim of this study was to investigate the role
      of HIF-1alpha-1772 C/T (P582S) and -1790 G/A (A588T) polymorphisms in the
      susceptibility to and severity of non-small-cell lung cancer (NSCLC). Using a
      case-control study design and polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) analysis, the allele frequencies and genotype
      distributions of each single nucleotide polymorphism in 285 NSCLC cases and 300
      gender-matched controls were compared. The distribution of the genotype
      frequencies of HIF-1alpha-1772 C/T and -1790 G/A were significantly different
      between the NSCLC and the controls. Logistic regression analysis revealed that
      higher odds ratios (ORs) for lung cancer were observed for individuals with HIF
      1alpha-1772 T/T genotype against CC/CT genotypes (an OR of 4.04, 95% confidence
      interval [CI] = 2.02-8.08, P = 0.0001), and HIF-1alpha-1790 A/A genotype against
      GG/GA genotypes (an OR of 4.42, 95% CI 2.22-8.78, P < 0.0001). There were no
      relationship between HIF-1alpha-1772 C/T or -1790 G/A allele distribution and
      disease severity of NSCLC (P > 0.05). However, those patients carrying a HIF
      1alpha-1772 T/T genotype or a HIF-1alpha-1790 A/A had a tendency toward inferior
      prognosis compared with other patients.

PMID- 22153810
TI  - Systemic administration of 3-bromopyruvate in treating disseminated aggressive
      lymphoma.
AB  - The Warburg hypothesis states that aggressive cancers obtain much of their
      adenosine triphosphate (ATP) by metabolizing glucose directly to lactic acid. As
      a result of its high tumor selectivity, 3-bromopyruvic acid (3-BrPA), a well
      known inhibitor of energy metabolism, has been proposed as a specific anticancer
      agent. We investigated the effect of 3-BrPA in a mouse model of aggressive
      metastatic lymphoma. Epstein-Barr-virus-infected human Raji lymphoma cells with
      lentivirally transfected green fluorescent protein and luciferase were incubated
      with RPMI/fetal bovine serum, and various concentrations of 3-BrPA were used to
      determine the LD50 in vitro. In total, 18 severely combined immunodeficient mice
      were injected with 1 million human Raji lymphoma cells via the tail vein. Using
      bioluminescent imaging, tumor growth was measured daily for 12 days to determine
      the tumor burden. At day 0 (start of treatment), the mice were randomized. Six
      mice received 10 mg/kg 3-BrPA i.p. daily for 7 days, 6 mice received 1 treatment
      at day 0, and 6 mice received the control buffer. Tumor growth was assessed daily
      from day 0 until day 7 using bioluminescent imaging. All data were normalized to
      acquisition time (luminescence/second; L/s). Body weight was measured daily to
      determine the toxicity of 3-BrPA. The LD50 for Raji lymphoma cells exposed to 3
      BrPA in vitro was 11 MUM with an extremely steep dose response curve. At day 0,
      tumor activity medians in the group with daily treatment was 2131 L/s (244
      12,725), with a 1-day dose of 3095 L/s (523-9650) and in the nontreated control
      group, 2997 L/s (1521-6911). In mice treated with a daily dose of 10 mg/kg 3-BrPa
      for 7 days, a significant reduction in tumor activity was found during the whole
      treatment period compared with the control mice (P = 0.0043 at day 7). In mice
      with a single treatment at day 0, growth delay was only evident at day 2 (P =
      0.0152 at day 2) but not for the rest of the observation period. The only
      manifestation of toxicity of the daily administration of 10 mg/kg 3-BrPA was a
      reduction in body weight. Body weight at day 0 was 17.22 g +/- 0.84 g in the
      treatment group and 17.58 g +/- 0.86 g in the control group. Body weight at day
      +6 was 15.02 g +/- 2.04 g in the treated group and 19.4 g +/- 0.63 g in the
      control group. 3-BrPA demonstrated a significant positive tumor response both in
      vitro and in vivo. This, to our knowledge, is the first report of the use of 3
      BrPA in a systemic tumor model. Based on these data, 3-BrPA holds promise for
      treatment of systemic metastatic cancers.

PMID- 22153811
TI  - Mitochondrial polymorphism 12361A>G is associated with nonalcoholic fatty liver
      disease.

PMID- 22153813
TI  - Comments regarding Vardoulis O, et al., Impact of aortic grafts on arterial
      pressure: a computational fluid dynamics study. Eur J Vasc Endovasc Surg
      2011;42:704-10.

PMID- 22153812
TI  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) preserves gut
      barrier function by blocking neutrophil-endothelial cell adhesion after
      hemorrhagic shock and resuscitation in mice.
AB  - BACKGROUND: We have shown that heparin-binding epidermal growth factor-like
      growth factor (HB-EGF) protects the intestines from injury in several different
      animal models, including hemorrhagic shock and resuscitation (HS/R). The current
      study was designed to explore the mechanisms underlying the anti-inflammatory
      role of HB-EGF in preservation of gut barrier function after injury. METHODS: In
      vivo, HS/R was induced in wild-type and neutropenic mice, with or without
      administration of HB-EGF, and intestinal permeability determined by use of the
      everted gut sac method. In vitro, cultured human umbilical vein endothelial cells
      (HUVECs) and freshly isolated human peripheral blood mononuclear cells (PMNs)
      were used to determine the effects of HB-EGF on HUVEC-PMN adhesion, reactive
      oxygen species production in PMN, adhesion molecule expression in HUVEC and PMN,
      and the signaling pathways involved. RESULTS: We found that administration of HB
      EGF to healthy mice led to preservation of gut barrier function after HS/R.
      Likewise, induction of neutropenia in mice also led to preservation of gut
      barrier function after HS/R. Administration of HB-EGF to neutropenic mice did not
      lead to further improvement in gut barrier function. In vitro studies showed that
      HB-EGF decreased neutrophil-endothelial cell (PMN-EC) adherence by down
      regulating adhesion molecule expression in EC via the phosphoinositide 3-kinase
      Akt pathway, and by inhibiting adhesion molecule surface mobilization and
      reactive oxygen species production in PMN. CONCLUSION: These results indicate
      that HB-EGF preserves gut barrier function by inhibiting PMN and EC activation,
      thereby blocking PMN-EC adherence after HS/R in mice, and support the future use
      of HB-EGF in disease states manifested by hypoperfusion injury.

PMID- 22153814
TI  - Molecularly imprinted polymer coated solid-phase microextraction fibers for
      determination of Sudan I-IV dyes in hot chili powder and poultry feed samples.
AB  - In this research, a novel strategy was developed to prepare molecularly imprinted
      polymer (MIP) coated solid-phase microextraction fibers on a large scale with
      Sudan I as template and stainless steel fibers as substrate. More than 20 fibers
      could be obtained in one glass tube, and the efficiency and coating repeatability
      were enhanced remarkably in contrast with the yield of only one fiber in our
      previous works. The obtained MIP-coated stainless steel fibers were characterized
      by homogeneous and highly cross-linked coating, good chemical and thermal
      stabilities, high extraction capacities, and specific selectivities to Sudan I-IV
      dyes. Based on the systemic optimization of extraction conditions, a simple and
      cost-effective method based on the coupling of MIP-coated SPME with high
      performance liquid chromatography was developed for the fast and selective
      determination of trace Sudan I-IV dyes in hot chili powder and poultry feed
      samples. The limits of detection of Sudan I-IV dyes were within 2.5-4.6 ng g(-1),
      and the spiked recoveries were in the range of 86.3-96.3% for hot chili powder
      sample and 84.6-97.4% for poultry feed sample.

PMID- 22153815
TI  - Microwave-assisted purge-and-trap extraction device coupled with gas
      chromatography and mass spectrometry for the determination of five predominant
      odors in sediment, fish tissues, and algal cells.
AB  - Off-flavors are among the most troublesome compounds in the environment
      worldwide. The lack of a viable theory for studying the sources, distribution,
      and effect of odors has necessitated the accurate measurement of odors from
      environmental compartments. A rapid and flexible microwave-assisted purge-and
      trap extraction device for simultaneously determining five predominant odors,
      namely, dimethyltrisulfide, 2-methylisoborneol, geosmin, beta-cyclocitral and
      beta-ionone, from the primary sources and sinks is demonstrated. This instrument
      facilitates the extraction and concentration of odors from quite different
      matrices simultaneously. This device is a solvent-free automated system that does
      not require cleaning and is timesaving. The calibration curves of the five odor
      compounds showed good linearity in the range of 1-500 ng/L, with correlation
      coefficients above 0.999 (levels=7) and with residuals ranging from approximately
      77% to 104%. The limits of detection (S/N=3) were below 0.15 ng/L in algae sample
      and 0.07 ng/g in sediment and fish tissue samples. The relative standard
      deviations were between 2.65% and 7.29% (n=6). Thus the proposed design is ready
      for rapid translation into a standard analytical tool and is useful for multiple
      applications in the analysis of off-flavors.

PMID- 22153816
TI  - Capillary size exclusion chromatography with picogram sensitivity for analysis of
      monoclonal antibodies purified from harvested cell culture fluid.
AB  - Size exclusion chromatography (SEC) is widely used in the characterization and
      quality control of therapeutic proteins to detect aggregates. Aggregation is a
      carefully monitored quality attribute from the earliest stages of clinical
      development owing to the possibility of eliciting an immunogenic response in the
      patient. During early stage molecule assessment for cell culture production,
      small-scale screening experiments are performed to permit rapid turn-around of
      results so as to not delay timelines. We report the development of a capillary
      SEC methodology for preliminary molecule assessment to support the evaluation of
      therapeutic candidates at an early stage of development. By making several key
      modifications to a commercially available liquid chromatography system, we
      demonstrate a platform process to perform capillary SEC with excellent precision,
      picogram sensitivity and good ruggedness. The limit of quantitation was
      determined to be approximately 15 pg; picogram sensitivity for SEC analysis of
      monoclonal antibodies had not been achieved prior to this work. In addition, we
      have developed a method to capture low levels of antibody (1 MUg/mL) from
      harvested cell culture fluid (HCCF) for capillary SEC analysis. Up to 40%
      recovery efficiency was achieved using this micro-recovery method on 3 mL HCCF
      samples. Using early stage cell culture transient transfection samples, which
      typically have much lower titers than stable cell line samples, we demonstrate a
      consistent method for analyzing aggregates in low protein concentration HCCF
      samples for molecule assessment and early stage candidate screening.

PMID- 22153817
TI  - Thinking beyond ourselves.

PMID- 22153818
TI  - Seeing well is the key to learning in a world of 3-D.

PMID- 22153819
TI  - Physiological causes of solar maculopathy. Letter.

PMID- 22153821
TI  - Demyelinating optic neuritis presenting as a clinically isolated syndrome.
AB  - BACKGROUND: Clinically isolated syndrome (CIS) describes a single, first
      occurrence attack caused by inflammation/demyelination in 1 or more locations in
      the central nervous system. The optic nerve is a frequent site affected by this
      neurologic event. As the name implies, CIS is an isolated condition but is often
      considered a precursor to multiple sclerosis (MS). When distinctive brain lesions
      detected by magnetic resonance imaging (MRI) accompany CIS, the person is
      considered at a high risk for MS. Treatment is aimed at delaying the onset of a
      second neurologic episode, reducing the accumulation of MRI-detected brain
      lesions and delaying the development of definite MS. CASE REPORT: This article
      describes a 40-year-old woman who experienced a sudden loss of vision in the
      right eye. Testing ultimately found a normal MRI, demyelination of the optic
      nerve, and progressive thinning of the retinal nerve fiber layer, leading to a
      diagnosis of CIS.

PMID- 22153822
TI  - Remote treatment of intermittent central suppression improves quality-of-life
      measures.
AB  - BACKGROUND: Intermittent central suppression (ICS) is a repetitive intermittent
      ("on-and-off") loss of central visual sensation without strabismus or amblyopia.
      These repetitive seconds-long suppressions have been suggested to create visual
      confusion and instability that would cause vision symptoms, contribute to reading
      complaints, and even impair reading. METHODS: Teacher-identified Job Corps
      students were diagnosed with ICS and then treated with 5-Hz electronic liquid
      crystal shutter alternate occlusion. RESULTS: Twenty-six young adult students
      (19.7+/-1.6 y) had their ICS treated over 5.9+/-3.7 months. Suppression periods
      decreased in length (P<0.0001) and "binocular" nonsuppressed periods increased in
      length (P<0.0001). Overall, College of Optometrists in Vision Development (COVD)
      quality-of-life (QOL) scores improved (P<0.0001), 16 reading behavior COVD QOL
      questions improved (P<0.0001), and individual QOL questions improved. Posttherapy
      reading scores (N=18) improved 3.7 (+/-2.6) years (P<0.0001). CONCLUSIONS:
      Treating ICS with electronic alternate occlusion reduced suppression periods,
      increased binocular periods, and improved symptoms as measured in the COVD QOL
      questionnaire. Positive changes also occurred in reading scores. These data
      suggest ICS should be considered a probable cause for symptoms of reading
      problems.

PMID- 22153824
TI  - Fibroblast growth factor 23 and CKD prognosis.

PMID- 22153823
TI  - Corneal collagen cross-linking: an introduction and literature review.
AB  - BACKGROUND: This literature review analyzes the scientific evidence available
      regarding corneal collagen cross-linking (CXL) as a treatment option for
      progressive keratectasia. METHODS: A literature search was performed using dates
      from 1990 to August 2010 regarding CXL Specific areas of focus for the literature
      review include safety and efficacy of the procedure as a stand-alone treatment or
      when used in conjunction with Intacs(r) corneal implants (Addition TechnologyTM)
      or photorefractive keratectomy (PRK). RESULTS: A total of 50 clinical trials and
      studies were identified, 20 of which met the inclusion criteria. Results of the
      included literature support the conclusion that CXL is a safe and efficacious
      treatment for progressive keratectasia. The results of CXL alone have shown
      stabilization or improvement in the maximum keratometry readings, best-corrected
      visual acuity, uncorrected visual acuity, and spherical and cylinder refractive
      measurements. CXL has been shown to enhance the effects of Intacs and has been
      proven successful when used in conjunction with PRK. CONCLUSION: CXL is an
      effective treatment for limiting the progression of keratectasia, thus reducing
      the need for penetrating keratoplasty. CXL has a similar side-effect profile and
      similar risk level as PRK.

PMID- 22153825
TI  - Continuous growth of remote intracerebral haematoma following angiographically
      successful endovascular embolisation of ruptured cerebral aneurysms.
AB  - We describe a poorly recognised and rare complication following the endovascular
      embolisation of ruptured cerebral aneurysms. Three patients with dense focal
      subarachnoid haemorrhage (SAH) developed continuous growth of remote
      intracerebral haematoma (ICH) following endovascular embolisation of a ruptured
      aneurysm. All endovascular procedures were conducted within less than 6 hours
      after the onset of SAH with systemic anticoagulation and were completed
      uneventfully; external ventricular drainage was subsequently inserted. Repeated
      CT scans revealed continuous growth of ICH remote from the aneurysm without
      aneurysmal rebleeding. The authors suggest that endovascular embolisation for a
      ruptured aneurysm under systemic anticoagulation within 6 hours after SAH onset
      may increase the risk of expanding haematomas, especially in patients with dense
      focal SAH.

PMID- 22153826
TI  - Human brain glioma stem cells are more invasive than their differentiated progeny
      cells in vitro.
AB  - Glioma, the most commonly occurring primary intracranial tumor, remains
      associated with a dismal outcome, despite the availability of multimodal
      therapies. Recently, however, the identification of brain glioma stem cells
      (BGSC) has opened up new avenues for research. BGSC are now accepted as the
      progenitor cells of gliomas and are thought to determine the biological features
      of the resulting tumors. Thus, the diffuse invasiveness of gliomas should also be
      theoretically driven by BGSC. However, little research effort has been directed
      at understanding the invasiveness of BGSC. In the present study, BGSC from eight
      surgical glioma specimens were cultured and identified. Using Matrigel invasion
      assays, the invasiveness of these cells was measured and compared with that of
      their respective differentiated progeny cells in vitro. For all eight clinical
      specimens, the BGSC were significantly more invasive than their differentiated
      progeny cells. These findings indicate a key role for BGSC in glioma infiltration
      and invasion. We also found that BGSC tended to aggregate and reform into new
      spheres after travelling into the Matrigel, preserving some of the morphological
      characteristics of the suspended cells. The invasiveness of the BGSC did not
      correlate with the pathological grade of glioma in the present study, so further
      investigations using larger sample sizes are needed to better understand the
      mechanisms underlying the invasiveness of BGSC.

PMID- 22153827
TI  - Hourly rounding in the emergency department: how to accelerate results.

PMID- 22153828
TI  - Diagnosis and treatment status of migraine: a clinic-based study in China.
AB  - OBJECTIVES: To investigate the prevalence and clinical characteristics of
      migraine, and to evaluate the current status of migraine diagnosis and treatment
      in neurological outpatients. METHODS: A face-to-face interview survey was
      conducted in the neurological clinic of a tertiary care hospital during a period
      of three months. A headache questionnaire for patients who consulted doctors with
      a chief complaint of headache was completed by a qualified and experienced
      physician in headache studies during the interview. Migraine diagnosis was made
      by physicians based on the criteria of the second edition of the International
      Classification of Headache Disorders. RESULTS: Of 9282 patients assessed, 19.5%
      (1806) complained of headache. The prevalence of migraine was
      23.8%(401/1683)among headache patients. The average age of migraineurs was 42.2+/
      13.1 years and 80.5% were female. Of all migraineurs, 68.6% had consulted a
      physician for headache in the previous one year, and only 13.5% had received a
      physician diagnosis of migraine. A total of 173 migraine patients (43.1%) had not
      taken any analgesic for acute treatment in the previous three months and only 11
      migraineurs (2.7%) had used preventative medications. Medication overuse was
      significantly more common in male than in female patients with migraine (P<0.01).
      CONCLUSIONS: Migraine is the most common headache disorder in the neurological
      clinic and it remains underrecognized and undertreated in China. Public health
      initiatives to improve diagnosis and treatment of migraine are needed.

PMID- 22153829
TI  - Characterization of the immunophenotype of the tumor budding and its prognostic
      implications in squamous cell carcinoma of the lung.
AB  - Tumor budding is morphologically defined as infiltration by small clusters of
      cancer cells. While the biological properties of budding cells in adenocarcinoma
      (decreased expression of adhesion molecules and of differentiation markers) have
      been elucidated, those of the cells in squamous cell carcinoma (SqCC) of the lung
      still remain to be clarified. We examined the clinicopathological data of 217
      patients with SqCC of the lung. Furthermore we evaluated the immunohistochemical
      properties of the budding cells. Tumor budding was observed in 83 (38.2%)
      patients. A statistically significant difference was observed in overall 5-year
      survival rates between the cases showing tumor budding and the cases not showing
      budding (45.6% vs. 64.0%, p<0.001). As compared with cancer cells forming solid
      nests, budding cells (BCs) exhibited reduced expression levels of the cellular
      adhesion molecules (E-cadherin; p=0.004, beta-catenin; p=0.002) and increased
      expression levels of laminin-5gamma2 (p=0.001). On the other hand, no significant
      differences in the staining scores for differentiation markers (p63 and
      podoplanin) were found between BCs and cancer cells forming nests. Multivariate
      analysis revealed that tumor budding was a significant independent prognostic
      factor in patients with SqCC of the lung (p=0.022). Tumor budding is an
      independent adverse prognostic factor in patients with SqCC of the lung. Although
      budding cells in SqCC exhibited reduced expression levels of the cellular
      adhesion molecules, the expression levels of specific differentiation markers
      were retained, suggesting that the budding mechanism in SqCC may differ, at least
      in part, from that in adenocarcinoma.

PMID- 22153830
TI  - Differences in metabolism between adeno- and squamous cell non-small cell lung
      carcinomas: spatial distribution and prognostic value of GLUT1 and MCT4.
AB  - BACKGROUND: Hypoxia leads to changes in tumor cell metabolism such as increased
      glycolysis. In this study, we examined the spatial distribution of the glycolysis
      and hypoxia related markers glucose transporter 1 (GLUT1) and monocarboxylate
      transporter 4 (MCT4) expression in relation to the vasculature in stage I, II and
      resectable stage IIIA NSCLC. Furthermore, associations of these markers with
      survival were investigated. METHODS: GLUT1 and MCT4 expression were determined in
      90 NSCLC fresh frozen biopsies using immunohistochemical techniques and a
      computerized image analysis system. Markers were analyzed for adenocarcinomas
      (n=41) and squamous cell carcinomas (n=34) separately. Eighty-four patients were
      retrospectively evaluated for relapse and survival. RESULTS: Squamous cell
      carcinomas demonstrated higher GLUT1 expression, relative to adenocarcinomas.
      Also, in squamous cell carcinomas, GLUT1 and MCT4 expression increased with
      increasing distance from the vasculature, whereas in adenocarcinomas upregulation
      of MCT4 was already found at closer distance from vessels. In adenocarcinomas,
      high GLUT1 expression correlated with a poor differentiation grade and positive
      lymph nodes at diagnosis. High GLUT1 plus high MCT4 expression was associated
      with a poor disease-specific survival in only adenocarcinomas (p=0.032).
      CONCLUSION: Analysis of GLUT1 and MCT4 expression on the histological level
      suggested a different metabolism for adenocarcinomas and squamous cell
      carcinomas. Likely, adenocarcinomas rely mainly on aerobic glycolysis for ATP
      production, whereas the behavior of squamous cell carcinomas is more
      physiologically, i.e. mitochondrial oxidation with anaerobic glycolysis under
      hypoxic conditions. High GLUT1 plus high MCT4 expression indicated an aggressive
      tumor behavior in adenocarcinomas. This subgroup of tumors may benefit from new
      treatment approaches, such as MCT4 inhibitors. Since this study has an
      exploratory character, our results warrant further investigation and need
      independent validation.

PMID- 22153831
TI  - Histologic subtypes, immunohistochemistry, FISH or molecular screening for the
      accurate diagnosis of ALK-rearrangement in lung cancer: a comprehensive study of
      Caucasian non-smokers.
AB  - EML4-ALK adenocarcinomas constitute a new molecular subgroup of lung tumours that
      respond very well to crizotinib, an ALK inhibitor. However, the diagnosis of ALK
      rearrangement in lung cancer is challenging. The aim of this study was to compare
      the diagnostic accuracy of five different methods in a series of 20 EGFR(wt/wt)
      lung adenocarcinomas from non- or light- smokers. Multiplex RT-PCR was considered
      as gold standard and identified four ALK-rearranged tumours among the 20 tested
      tumours. qRT-PCR got an interpretability rate of 100% and accurately typed all 20
      tumours. qRT-PCR from corresponding formalin-fixed paraffin-embedded (FFPE)
      specimens got an interpretability rate of 65%. Out of the four previously
      identified ALK-rearranged cases, three were interpretable and two were retrieved
      using FFPE qRT-PCR. ALK break-apart FISH got an interpretability rate of 60% and
      accurately typed all of the twelve remaining cases. Anti-ALK immunohistochemistry
      (IHC) accurately typed all twenty tumours using a cut-off value of strong
      staining of 100% tumour cells. The 16 non ALK-rearranged tumours got no/light
      staining in 13 cases, and a moderate staining of 80-100% tumour cells in 3 cases.
      We then analysed four solid signet-ring lung adenocarcinomas. FFPE qRT-PCR, FISH
      and immunohistochemistry were concordant in three cases, with positive and
      negative results in respectively one and two cases. The fourth case, which was
      positive by FISH and immunohistochemistry but negative by RT-PCR, was shown to
      have a non-EML4-ALK ALK-rearrangement. As various factors such as RNA quality,
      fixation quality and type of ALK rearrangement may impede ALK screening, we
      propose a combined FISH/molecular biology diagnostic algorithm in which anti-ALK
      immunohistochemistry is used as a pre-screening step.

PMID- 22153832
TI  - Carcinoembryonic antigen (CEA) as tumor marker in lung cancer.
AB  - The use of CEA as a prognostic and predictive marker in patients with lung cancer
      is widely debated. The aim of this review was to evaluate the results from
      studies made on this subject. Using the search words "CEA", "tumor markers in
      lung cancer", "prognostic significance", "diagnostic significance" and
      "predictive significance", a search was carried out on PubMed. Exclusion criteria
      was articles never published in English, articles before 1981 and articles
      evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles
      were found, and 34 were left after selecting those relevant for the present
      study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small
      Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients.
      Regarding SCLC no studies showed that serum level of CEA was a prognostic marker
      for overall survival (OS). The use of CEA serum level as a prognostic marker in
      NSCLC was investigated in 23 studies and the use of CEA plasma level in two. In
      18 (17 serum, 1 plasma) of these studies CEA was found to be a useful prognostic
      marker for either OS, recurrence after surgery or/and progression free survival
      (PFS) in NSCLC patients. Interestingly, an overweight of low stage (stage I-II)
      disease and adenocarcinoma (AC) patients were observed in this group. The
      remaining 7 studies (6 serum, 1 plasma) contained an overweight of patients with
      squamous carcinoma (SQ). One study found evidence for that a tumor marker index
      (TMI), based on preoperative CEA and CYFRA21-1 serum levels, is useful as a
      prognostic marker for OS in NSCLC. Six studies evaluated the use of CEA as a
      predictive marker for risk of recurrence and risk of death in NSCLC patients.
      Four of these studies found, that CEA was useful as a predictive marker for risk
      of recurrence and risk of death measured over time. No studies found CEA levels
      useful as a diagnostic marker for lung cancer. With regard to NSCLC the level of
      CEA measured in tumor tissue in NSCLC patients, were not of prognostic,
      diagnostic or predictive significance for OS or recurrence after treatment. In
      one study CEA level was measured in Pleural Lavage Fluid (PLF) it was here found
      to be useful as prognostic markers for overall survival (OS) after surgery. In
      conclusion serum level of CEA carries prognostic and predictive information of
      risk of recurrence and of death in NSCLC independent of treatment or study
      design. The observation that TMI index could be a potential prognostic marker for
      OS in NSCLC is interesting. Future studies may benefit from evaluating more than
      one marker at a time, which may possibly create a more precise index for
      prognosis and recurrence in lung cancer, than is possible by the use of single
      biomarkers.

PMID- 22153833
TI  - Exploring application of the Interpersonal-Psychological Theory of Suicidal
      Behaviour to self-injurious behaviour among women prisoners: Proposing a new
      model of understanding.
AB  - The current study examines the application of capacity, psychological distress,
      coping and personality to an understanding of self-injurious behaviour, with a
      specific focus on testing the Interpersonal-Psychological Theory of Suicidal
      Behaviour (IPTSB). One hundred and ninety women prisoners took part, completing a
      history questionnaire and measures of personality, coping styles and
      psychological distress. It was expected that self-injurious behaviour would be
      predicted by higher levels of emotional functioning difficulties, by an increased
      capacity to engage in such behaviours, by previous self-injurious behaviour,
      decreased levels of emotional stability and increased levels of emotional coping
      behaviour. Results supported the capacity component of the IPTSB, indicating that
      an increased history of self-injurious behaviour and of engagement in reckless
      behaviour were particular predictors. Increased psychological distress in some
      domains was also a predictor although the exact domain varied across the type of
      self-injurious engagement Increased levels of extraversion and decreased
      emotional coping predicted increased self-injurious engagement, although
      emotional coping only related to threats and cognition. The results point to the
      applicability of Interpersonal-Psychological Theory to understanding self
      injurious behaviour and the importance of developing a revised model. The paper
      presents this in the form of the Integrated Model of Self-Injurious Activity.

PMID- 22153834
TI  - Facial emotion recognition in Scottish prisoners.
AB  - BACKGROUND: Studies of antisocial populations have found that they show deficits
      in recognition of facial affect. Such deficits are also found in other
      populations with clinical conditions such as autism spectrum disorders,
      schizophrenia and obsessive compulsive disorder. AIMS: We aimed to investigate
      the hypothesis that facial affect recognition in the Scottish prison population
      would differ from matched controls. In addition, we aimed to investigate any
      relationship between facial affect recognition deficits and offence history.
      METHODS: A sample of serving convicted prisoners, drawn from a larger study, was
      assessed for ability to recognise facial affect. Other variables were also
      measured and a self-report offending history obtained. RESULTS: 127 prisoners
      were assessed in 11 prisons. Male prisoners were significantly worse than age,
      sex and IQ-matched controls at recognising negative facial emotions, specifically
      anger, fear, sadness and disgust. Within the sample of prisoners, deficits in
      fear recognition were associated with a history of previous prison sentences but
      not previous convictions. With respect to offending history, sex offenders were
      relatively better at recognising sadness and worse at recognising surprise than
      the other offenders. These relationships remain after controlling for IQ.
      CONCLUSIONS: Scottish convicted prisoners show deficits in recognising negative
      facial emotions in a pattern consistent with other antisocial populations. We
      also demonstrated a relationship between particular patterns of deficit and types
      of offending history not previously described.

PMID- 22153835
TI  - High PEGylation efficiency of pentaethylenehexamine-end poly(ethylene glycol)
      (mPEG-N6) for active-ester surface.
AB  - The chemical surface-modification of carboxylated polystyrene submicroparticles
      (sMPs) with alpha-methoxy-poly(ethylene glycol)-pentaethylenehexamine (mPEG-N6),
      which possesses multiple amino end-groups at one end, was explored with respect
      to modification efficiency. As a control, a PEG mono-aminated at one end (mPEG
      N1) was employed in parallel experiments. Dynamic light scattering (DLS),
      electrophoretic mobility (MU(e)), Fourier transform infra-red (FT-IR) absorption,
      and 3-(p-carboxybenzoyl)quinoline-2-caboxaldehyde (CBQCA) assays were carried
      out. From reported pK(a) values of the amino groups, about 25% of the amino
      groups were protonated at pH9.5 for pentaethylenehexamine (N6), in other words,
      1.5 amino groups were protonated and 4.5 amino groups were non-protonated on
      average for each mPEG-N6 molecule under the conditions. The multiple amino end
      groups of mPEG-N6 played two different roles in modifying the sMPs: the
      protonated part offered electrostatic attraction between mPEG-N6 and the
      negatively charged sMPs; the non-protonated part covalently reacted with the
      active ester groups on the sMP surface after EDC-activation treatments. During
      the PEG-modification process, the former attractive force increased the local
      mPEG-N6 concentration surrounding the sMPs, which facilitated covalent
      conjugation to the sMPs. In contrast, protonated mPEG-N1 (80% under the same
      conditions) tends to cover the negatively charged sMPs, which retards the
      reaction of non-protonated mPEG-N1. These collaborative actions within each mPEG
      N6 chain improved the PEG-modification efficiency, rending mPEG-N6 an ideal
      PEGylation agent relative to mPEG-N1.

PMID- 22153837
TI  - REM sleep could have no adaptive value.

PMID- 22153836
TI  - Attachment of bacteriophages MS2 and PhiX174 onto kaolinite and montmorillonite:
      extended-DLVO interactions.
AB  - This study aims to gain insights into the interaction of virus particles with
      clay colloids. Bacteriophages MS2 and PhiX174 were used as model viruses and
      kaolinite (KGa-1b) and montmorillonite (STx-1b) as model colloids. The
      experimental data obtained from batch experiments of MS2 and PhiX174 attachment
      onto KGa-1b and STx-1b suggested that virus attachment is adequately described by
      the Freundlich isotherm equation. Both MS2 and PhiX174 were attached in greater
      amounts onto KGa-1b than STx-1b with MS2 having greater affinity than PhiX174 for
      both clays. Furthermore, extended-DLVO interaction energy calculations explained
      that the attachment of viruses onto model clay colloids was primarily caused by
      hydrophobic interaction. The theoretical and experimental results of this study
      were found to be in good agreement with previous findings.

PMID- 22153838
TI  - Microheliella maris (Microhelida ord. n.), an ultrastructurally highly
      distinctive new axopodial protist species and genus, and the unity of phylum
      Heliozoa.
AB  - A new heliozoan, Microheliella maris, has sufficiently distinctive ultrastructure
      to merit a new order, Microhelida. Its 18S and 28S rRNA genes were sequenced
      earlier under the informal name 'marine microheliozoan'; we here sequenced its
      Hsp90 gene. A three-gene tree suggests that it is distantly related to
      centrohelids and others in chromist subkingdom Hacrobia; but it is too divergent
      to be placed accurately by few genes. Unlike centrohelids, its central spherical
      centrosome has two concentric granular shells and a dense core devoid of a
      trilaminar central disc. Microtubules radiate from the centrosomal shells. Unlike
      centrohelids, axopodia have only three microtubules, fixed basally by dense
      plasma membrane anchors, and bear terminal and lateral haptosome-like extrusomes.
      As in the heliomonad Heliomorpha, the centrosome is embedded in a nuclear cavity,
      and centrosomal microtubules traverse the nucleus inside cytoplasmic channels. A
      novel filogranular network interconnects mitochondria, ER, and plasma membrane.
      The microbody is attached to the nucleus and mitochondrion, which has vermicular
      tubular cristae. We group Microhelida and Heliomonadida, purged of dissimilar
      flagellates, as a new tubulicristate class Endohelea within phylum Heliozoa.
      Previously misassigned GenBank 18S rDNA sequences reveal Microhelida as diverse
      and ancient. We discuss principles underlying the biogenesis and diversity of
      axopodial patterns.

PMID- 22153839
TI  - Physical activity is independently associated with multiple measures of arterial
      stiffness in adolescents and young adults.
AB  - Physical activity (PA) is associated with decreased levels of arterial stiffness
      in adults, but the relationship between PA and multiple measures of arterial
      stiffness in adolescents and young adults is not clear. The objective of this
      study was to test the hypothesis that PA is an independent predictor of multiple
      measures of arterial stiffness in adolescents and young adults. A total of 548
      participants were enrolled in a study of the cardiovascular effects of obesity
      and type 2 diabetes mellitus (T2DM) (lean, 201; obese, 191; T2DM, 156).
      Anthropometrics, blood pressure, central and peripheral measures of arterial
      stiffness (pulse wave velocity, brachial distensibility, and augmentation index),
      blood (lipids and metabolic tests), and accelerometry data were collected.
      General linear modeling was performed to test for the independent relationship of
      PA on arterial stiffness. The mean age of the participants was 17.9 years
      (standard deviation, 3.5 years). After adjusting for other cardiovascular disease
      risk factors such as age, sex, body size, mean arterial pressure, and the
      presence of obesity or T2DM, PA was an independent predictor of augmentation
      index and brachial distensibility (P < .001). A greater effect of PA on pulse
      wave velocity was found in participants with T2DM (P = .009) compared with
      participants in the lean or obese groups. Physical activity is significantly and
      independently associated with multiple measures of arterial stiffness in
      adolescents and young adults. The role of PA in the prevention of cardiovascular
      disease target organ damage in youth, independent of energy balance, merits
      further exploration.

PMID- 22153840
TI  - Administration of hydrogen-saturated saline decreases plasma low-density
      lipoprotein cholesterol levels and improves high-density lipoprotein function in
      high-fat diet-fed hamsters.
AB  - Hydrogen (dihydrogen; H(2)) has an antiatherosclerotic effect in apolipoprotein
      (apo) E knockout mice. The goals of this study were to further characterize the
      effects of H(2) on the content, composition, and biological activities of plasma
      lipoproteins in golden hamsters. Plasma analysis by enzymatic method and fast
      protein liquid chromatography showed that 4-week intraperitoneal injection of
      hydrogen-saturated saline remarkably decreased plasma total cholesterol and low
      density lipoprotein (LDL) cholesterol levels in high-fat diet-fed hamsters.
      Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of
      apolipoproteins from ultracentrifugally isolated plasma lipoproteins revealed a
      marked decrease of apo B100 and apo B48 in LDL. A profound decrease of apo E
      level in very low-density lipoprotein was also observed. Besides, we determined
      the functional quality of high-density lipoprotein (HDL) particles isolated from
      H(2)-treated and control mice. H(2) significantly improved HDL functionality
      assessed in 2 independent ways, namely, (1) stimulation of cholesterol efflux
      from macrophage foam cells by measuring HDL-induced [(3)H]cholesterol efflux and
      (2) protection against LDL oxidation as a measure of Cu(2+)-induced
      thiobarbituric acid reactive substances formation. Administration of hydrogen
      saturated saline decreases plasma LDL cholesterol and apo B levels and improves
      hyperlipidemia-injured HDL functions, including the capacity of enhancing
      cellular cholesterol efflux and playing antioxidative properties, in high-fat
      diet-fed hamsters.

PMID- 22153841
TI  - Psychological morbidity and facial volume in HIV lipodystrophy: quantification of
      treatment outcome.
AB  - HIV lipoatrophy is a stigmatizing condition associated with significant
      psychological morbidity. The aim of this study was to evaluate change in facial
      volume and psychological morbidity following treatment with autologous fat,
      Sculptra and Bio-alcamid. METHODS: HIV LD patients were treated based on a
      clinical assessment in a prospective, observational study. 3-D images were
      obtained pre-operatively then at 2, 6 and 12 months post-operatively using the
      DI3D system. Volume changes were measured using DI3D software. The DAS-24 and
      HADS were used to assess psychological morbidity at similar time intervals.
      RESULTS: Forty-eight patients with HIV LD were treated: 16 patients had Bio
      alcamid, 20 patients received Sculptra and 12 patients underwent fat transfer.
      The mean injected volume of Bio-alcamid was 25.5 cc which was comparable to the
      measured volume change at follow-up. The mean injected volume of fat was 20.1 cc,
      which did not differ from the measured volumes at 2 months. There was a mean
      reduction in measured volume change to11.2 cc at 6 months and 10 cc at 12 months.
      For Sculptra, the mean volume change compared to baseline was 8.7 cc at 2 months,
      increasing to 12.6 cc at 6 months and 12.3 cc at 12 months. ANOVA tests
      demonstrated no difference in psychological outcomes between groups. There was a
      significant improvement in DAS-24 scores compared to baseline for all 3 groups.
      No correlation between change in facial volume and psychological measures was
      demonstrated. CONCLUSIONS: Change in 3-D measured facial volume for all 3 groups
      was seen. Treatment was associated with improved body image perception.

PMID- 22153842
TI  - The cubital tunnel syndrome caused by the two synovial cysts.
AB  - The cubital tunnel syndrome caused by several synovial cysts has been rarely
      reported. In our case, a 63-year-old man had sensorial and motor complaints at
      the ring and little fingers of the right hand. The claw deformity and the atrophy
      of the hypothenar and interosseous muscles in the right hand were discovered on
      physical examination. Froment's sign was positive. Electromyography showed
      prolonged distal latencies and slowed conduction for ulnar nerve. A small
      spherical cyst within the cubital tunnel and another spindle-shaped cyst at the
      distal to the cubital tunnel were found to compress and wrap the ulnar and its
      branches intra-operatively. Finally, the cysts were removed and the ulnar nerve
      was decompressed and performed its anterior transposition. Synovial cysts were
      confirmed by histopathological examination.

PMID- 22153843
TI  - Identification of a novel nidovirus associated with a neurological disease of the
      Australian brushtail possum (Trichosurus vulpecula).
AB  - A novel, fatal neurological disease of the Australian brushtail possum
      (Trichosurus vulpecula) was first identified in 1995 in a research facility and
      subsequently in free-living possums in New Zealand and termed wobbly possum
      disease (WPD). The results of previous transmission studies suggested that the
      aetiological agent of WPD is most likely a virus. However, the identity of the
      presumed viral agent had not been elucidated. In the current report, we describe
      identification of a novel virus from tissues of WPD-affected possums using a
      combination of next generation sequencing and traditional molecular methods. The
      proportion of possums positive for the novel virus by PCR was significantly
      higher (p<0.0001) among animals with WPD than clinically healthy possums,
      strongly suggesting an aetiological involvement of the virus in WPD. Analysis of
      the partial genomic sequence of the putative WPD virus indicated that it is a
      novel nidovirus, most closely related to the current members of the family
      Arteriviridae.

PMID- 22153844
TI  - Changes in the gene expression profile of Acetobacter aceti during growth on
      ethanol.
AB  - Acetobacter aceti NBRC 14818 shows a diauxic growth profile and temporarily
      accumulates acetate when grown in medium containing ethanol. However, the
      mechanisms underlying the metabolic switching between the incomplete oxidation of
      ethanol and overoxidation of acetate, and the control of stress resistance
      systems in A. aceti cells grown on ethanol are not fully understood. In this
      study, time-dependent transcriptome changes in cells during growth on ethanol
      were analyzed by DNA microarray. In A. aceti, ethanol is oxidized to acetate via
      acetaldehyde by sequential reactions of alcohol dehydrogenase (ADH) and aldehyde
      dehydrogenase (ALDH). We found that the genes encoding pyrroloquinoline quinone
      dependent ADH, membrane-bound ALDH, and two NAD(+)-ADHs were expressed
      constitutively in cells throughout the culture period. In contrast, the
      expression levels of genes encoding tricarboxylic acid (TCA) cycle enzymes were
      low during acetate accumulation until ethanol was consumed, but were
      significantly upregulated after the accumulated acetate was started to be
      consumed. This result suggests that changes in the carbon metabolic flow through
      the TCA cycle are important for the metabolic switching from acetate accumulation
      to the overoxidation of acetate. In addition, the genes for glyoxylate pathway
      enzymes were significantly upregulated soon after the cells began oxidizing
      ethanol, indicating that this pathway is important for the utilization of ethanol
      as a carbon source.

PMID- 22153845
TI  - Application of electrospray ionization ion trap/time-of-flight mass spectrometry
      for chemically-synthesized small RNAs.
AB  - In this study, we have demonstrated an accurate and rapid small RNA analytical
      method with both sequence determination and detailed modification analysis by
      electrospray ionization-ion trap/time-of-flight mass spectrometry (ESI-IT/TOFMS).
      To develop this ideal method, we have examined the performance of ESI-IT/TOFMS
      using various chemically-synthesized model sequences of modified or unmodified
      microRNAs (miRNAs). The deconvoluted mass of a 22-nucleotide (nt) miRNA was
      obtained from a multiply charged precursor ion (MS(1)). The ion exhibited high
      mass accuracy (< 7 ppm) and high mass resolution (a value of m/Deltam=10,000) and
      was therefore very useful in RNA composition assignment. The optimized MS(2)
      method using ion trap collision-induced dissociation, as well as automatic
      annotation analysis of product ions based on the accurate mass information,
      enabled the precise sequencing determination of intact miRNAs. Further, the
      detailed structural analysis of 3'-terminal modified nucleic acid in intact
      methylated miRNA was carried out using the MS(3) capability of the hybrid
      IT/TOFMS. The direct infusion method also provided a high throughput and good
      sensitivity because the analytical time and sample concentration needed in a
      series of experiments with reliable data were only 3 min and 100 nM,
      respectively. This study provides a novel approach for characterizing the intact
      chemically-synthesized small RNA without chemical and enzymatic digestions and
      would be widely applicable for the structural analysis of complicated modified
      small RNAs.

PMID- 22153846
TI  - A call for consideration of needlestick injury data in evaluating staffing
      effectiveness.

PMID- 22153847
TI  - Real-time polymerase chain reaction testing for Clostridium difficile reduces
      isolation time and improves patient management in a small community hospital.
AB  - BACKGROUND: The impact of a switch from a toxin A/B enzyme immunoassay (EIA) to a
      polymerase chain reaction (PCR) method for detection of toxigenic Clostridium
      difficile was assessed for C difficile infection (CDI) rates, patient isolation
      days, and CDI-related treatment. METHODS: A 6-month retrospective study was done
      on symptomatic patients tested by the toxin A/B EIA and PCR assays. Data on the
      number of C difficile tests ordered, patient isolation-days, and treatment with
      metronidazole or vancomycin were collected. CDI rates were reported as cases per
      10,000 patient-days, and differences between both groups were compared by chi(2)
      and Z-test analysis. RESULTS: The CDI incidence was 11.2 and 12.7/10,000 patient
      days in the EIA and PCR test periods, respectively (P = .36). Health care
      associated CDI decreased from 4.4 per 10,000 patient-days during EIA testing to
      0.9 per 10,000 patient-days during PCR testing (P = .02). A significant decrease
      in patient isolation-days (P < .00001), tests ordered (P = .002), and
      metronidazole treatment for patients with a negative C difficile test (P = .02)
      was observed with PCR testing. CONCLUSION: PCR testing is a viable option for
      small community hospitals, providing accurate and timely results for patient
      management and infection control. This can potentially lead to improved outcomes,
      increased patient satisfaction, and significant hospital cost savings.

PMID- 22153849
TI  - Blood glucose measurement for flap monitoring to salvage flaps from venous
      thrombosis.
AB  - Early detection and rapid re-exploration are important for flap salvage, and for
      this, a reliable monitoring method is required. The purpose of the current study
      was to evaluate blood glucose measurement (BGM) for flap monitoring and to
      establish a simple method that can be used widely to decrease the flap loss rate
      after tissue transplantation. We noted the BGM in 33 free or pedicled tissue
      transfers (57 BGM points) over time postoperatively. Skin punctures and blood
      glucose measurements were made using a Medisafe-finetouch needle and Medisafe
      Mini (Terumo, Japan), which are commonly used by diabetic patients. Partial
      necrosis of the vascular territory was found at 5 points (9%), and blood flow
      disorder due to a venous thrombus was found at 5 points (9%). The mean blood
      glucose level in the congestive flaps was significantly lower than that in
      healthy flaps. ROC curve analysis was used to determine a cutoff value for BGM of
      62 mg/dL, at which the sensitivity and specificity were 88% and 82%, respectively
      (p < 0.0001). In conclusion, BGM is an easy and accessible adjunct to flap
      monitoring, and the combination of BGM and previously established methods is
      likely to reduce postoperative complications caused by the development of a
      venous thrombus after free tissue transplantation.

PMID- 22153851
TI  - Co-delivery of antigen and a lipophilic anti-inflammatory drug to cells via a
      tailorable nanocarrier emulsion.
AB  - Nanotechnology promises new drug carriers that can be tailored to specific
      applications. Here we report a new approach to drug delivery based on tailorable
      nanocarrier emulsions (TNEs), motivated by a need to co-deliver a protein antigen
      and a lipophilic drug for specific inhibition of nuclear factor kappa B (NF
      kappaB) in antigen presenting cells (APCs). Co-delivery for NF-kappaB inhibition
      holds promise as a strategy for the treatment of rheumatoid arthritis. We used a
      highly surface-active peptide (SAP) to prepare a nanosized emulsion having
      defined surface properties predictable from the SAP sequence. Incorporating the
      lipophilic drug into the oil phase at the time of emulsion formation enabled its
      facile packaging. The SAP is depleted from bulk during emulsification, allowing
      simple subsequent addition of the drug-loaded oil-in-water emulsion to a solution
      of protein antigen. Decoration of emulsion surface with antigen was achieved via
      electrostatic deposition. In vitro data showed that the TNE prepared this way was
      internalized and well-tolerated by model APCs, and that good suppression of NF
      kappaB expression was achieved. This work reports a new type of nanotechnology
      based carrier, a TNE, which can potentially be tailored for co-delivery of
      multiple therapeutic components, and can be made using simple methods using only
      biocompatible materials.

PMID- 22153850
TI  - Low prevalence of Pneumocystis jirovecii lung colonization in Ugandan HIV
      infected patients hospitalized with non-Pneumocystis pneumonia.
AB  - Pneumocystis jirovecii is an important opportunistic infection in human
      immunodeficiency virus (HIV)-infected patients. In the developed world, P.
      jirovecii epidemiology is marked by frequent colonization in immunosuppressed
      patients, but data on the prevalence of colonization are very limited in sub
      Saharan Africa, where the majority of persons living with HIV reside. Our
      objective was to describe the epidemiology of P. jirovecii colonization among HIV
      positive patients in a cross-sectional, hospital-based study of patients admitted
      with suspected pneumonia in Kampala, Uganda. P. jirovecii was detectable in
      bronchoalveolar lavage fluid from 7 (6%) of 124 consecutive patients with non
      Pneumocystis pneumonia. Colonization was not associated with patient demographic
      or clinical information. This prevalence is substantially lower than in published
      studies in the developed world and suggests that there is a limited reservoir of
      organisms for clinical infections in this Ugandan population. These findings may
      partially explain the low incidence of Pneumocystis pneumonia in Uganda and other
      sub-Saharan African countries.

PMID- 22153852
TI  - Preparation and characterization of uniform drug particles: dehydrocholic acid.
AB  - Two methods for the preparation of uniform dispersions of dehydrocholic acid of
      different morphologies are described. In the first case, the drug was dissolved
      in acetone and then re-precipitated by adding a non-solvent (either water or an
      aqueous stabilizer solution), which yielded rod-like particles. In the second
      procedure, spheres, consisting of small elongated subunits, were obtained by
      acidification of basic aqueous solutions of the drug. The resulting particles
      were characterized in terms of their structure and surface charge
      characteristics.

PMID- 22153853
TI  - Thermally stable organically modified layered silicates based on alkyl
      imidazolium salts.
AB  - A series of imidazolium salts having various substituents and functional groups
      were synthesized and characterized by FTIR and NMR spectroscopy. Organic
      modification of natural and synthetic layered silicates involving montmorillonite
      (MMT), laponite (lap), and synthetic mica (mica) was carried out by ion-exchange
      reaction. The obtained organo-clays were characterized by FTIR and powder X-ray
      diffraction techniques. Results indicate that these organically modified clays
      have much higher thermal stabilities compared to their corresponding imidazolium
      halides. It was also observed from TGA analysis that thermal stability does not
      depend on the functional group present at the 3-position of the imidazolium
      salts. These studies strongly supports premise that the removal of halide is
      necessary to improve the thermal stability of the organo-clay produced.

PMID- 22153854
TI  - Effect of water-soluble polymers, polyethylene glycol and poly(vinylpyrrolidone),
      on the gelation of aqueous micellar solutions of Pluronic copolymer F127.
AB  - The micellization of F127 (E(98)P(67)E(98)) in dilute aqueous solutions of
      polyethylene glycol (PEG6000 and PEG35000) and poly(vinylpyrrolidone) (PVP K30
      and PVP K90) is studied. The average hydrodynamic radius (r(h,app)) obtained from
      the dynamic light scattering technique increased with increase in PEG
      concentration but decreased on addition of PVP, results which are consistent with
      interaction of the micelles with PEG and the formation of micelles clusters, but
      no such interaction occurs with PVP. Tube inversion was used to determine the
      onset of gelation. The critical concentration of F127 for gelation increased on
      addition of PEG and of PVP K30 but decreased on addition of PVP K90. Small-angle
      X-ray scattering (SAXS) was used to show that the 30 wt% F127 gel structure (fcc)
      was independent of polymer type and concentration, as was the d-spacing and so
      the micelle hard-sphere radius. The maximum elastic modulus (G(max)(')) of 30 wt%
      F127 decreased from its value for water alone as PEG was added, but was little
      changed by adding PVP. These results are consistent with the packed-micelles in
      the 30 wt% F127 gel being effectively isolated from the polymer solution on the
      microscale while, especially for the PEG, being mixed on the macroscale.

PMID- 22153855
TI  - Mitral and tricuspid valve repair and growth in unbalanced atrial ventricular
      canal defects.
AB  - OBJECTIVE: Congenital mitral and tricuspid valve abnormalities in unbalanced
      atrioventricular canal defects are complex. We designed procedures to both repair
      and induce growth of hypoplastic atrioventricular valves and ventricles to
      achieve 2-ventricle repairs. Midterm data were assessed for reliability of catch
      up growth, resulting quality of atrioventricular valves, and adequacy of 2
      ventricle repairs. METHODS: The 24 consecutive infants (14 female and 10 male)
      with unbalanced atrioventricular canal defects had significant hypoplasia of 1
      atrioventricular valve and/or ventricle (an echocardiography-derived z value of
      <=-3.0 standard errors of the mean below expected). Operative approaches included
      the following: (1) Staged repair was performed, with complete valve repair,
      partial closure of the atrial septal, and ventricular septal defects, and
      (usually) pulmonary artery banding. After adequate growth, repair was completed.
      A vestigial mitral valve (4-7 mm) in 3 patients led to partitioning the large
      tricuspid valve, creating a second mitral valve. (2) Repair with a shift in
      atrioventricular valve partitioning was performed to increase hypoplastic
      atrioventricular valve size. (3) Repair with snared atrial septal defects and
      ventricular septal defect was performed to allow intracardiac shunting. The
      hypoplastic atrioventricular valves and hypoplastic ventricles were reassessed on
      local follow-up (5-15 years). RESULTS: The initial z scores were -2.8 to -7.4 for
      hypoplastic atrioventricular valves and -1.0 to -7.5 for hypoplastic ventricles.
      Follow-up z scores were -0.6 to -2.7 for hypoplastic atrioventricular valves and 
      2.0 to +1.8 for hypoplastic ventricles. Another 11 patients were also judged to
      be within normal limits. Three reoperations were for mitral valve regurgitation,
      and 1 reoperation was for mitral valve replacement. One patient died of central
      nervous system bleed just before extracorporeal membrane oxygenation weaning, and
      2 patients died of late potassium overdose, for an 88% survival. Survivors are
      well with 2-ventricle repairs, and 15 of 19 patients are not taking cardiac
      medications. CONCLUSIONS: Increasing atrioventricular valve flow reliably induced
      growth. Valve repair and growth achieved a 2-ventricle repair in all patients.

PMID- 22153856
TI  - False appearance of bilateral pneumothorax in a patient with hypoplastic left
      lung.

PMID- 22153858
TI  - The universal bed model for patient care improves outcome and lowers cost in
      cardiac surgery.
AB  - OBJECTIVE: With the escalating demands to increase the efficiency and decrease
      the cost, innovations in postoperative cardiac surgical patient care are needed.
      The universal bed model is an innovative care delivery system that allows patient
      care to be managed in one setting from postoperation to discharge. We
      hypothesized that the universal bed model in the context of cardiac surgery would
      improve outcomes and efficacy. METHODS: A total of 610 consecutive patients were
      admitted to the universal bed unit and prospectively entered into the Society of
      Thoracic Surgeons National Cardiac Database. Intensive care unit level of care
      was determined by acuity and staffing needs. Telemetry was employed from
      admission to discharge, and multidisciplinary rounds were conducted twice daily.
      Postoperative outcomes were recorded during hospital stay, and comparisons were
      made with the Society of Thoracic Surgeons National Cardiac Database using
      identical variables over the same period of time. RESULTS: Decreased ventilation
      time, intensive care unit and hospital stay, and reduction in the incidence of
      atrial fibrillation and infectious complications yielded a financial benefit in
      the universal bed group compared with the traditional model of admission. Stroke
      rate and in-hospital mortality were the same compared with regional and national
      centers. Compared with regional centers, there was an average cost savings
      between $6200 and $9500 per patient depending on the operation. Patient care
      satisfaction by independent survey was in the 99th percentile. CONCLUSIONS: The
      universal bed patient care model allows for expedient and efficacious care as
      measured by decreased length of intensive care unit and hospital stay, improved
      postoperative outcomes, patient satisfaction, and cost savings.

PMID- 22153859
TI  - Coronary artery perfusion and myocardial performance after patent ductus
      arteriosus ligation.
AB  - OBJECTIVES: To study coronary artery (CA) perfusion and myocardial performance
      after patent ductus arteriosus (PDA) ligation. The postoperative course in
      premature infants undergoing surgical ligation of PDA is often complicated by
      cardiorespiratory instability secondary to impaired left ventricular performance.
      METHODS: Serial echocardiography was performed before and after (1, 8, and 24
      hours) PDA ligation to assess systolic (left ventricular output [LVO]) and
      diastolic (isovolumic relaxation time, E and A wave peak velocity) myocardial
      performance, and CA diastolic flow (CA velocity time integral and flow). The
      ratio of CA flow to LVO was calculated as a surrogate of coronary flow. RESULTS:
      A total of 20 infants (gestational age at birth, 26.3 +/- 0.7 weeks) requiring
      PDA ligation at a median of 28.5 days (range, 9-40) after birth and weight of 780
      g (range, 570-2840) were studied. A postoperative increase in the CA flow/LVO
      ratio was demonstrated. An early decrease in E and A wave peak velocity (P < .05)
      and increase in isovolumic relaxation time (P < .05) were demonstrated at 1 hour,
      before any clinical deterioration. A low baseline CA velocity time integral was
      associated with a low E/A ratio (r = 0.63, P = .01) at 1 hour and lower systolic
      blood pressure at 8 hours (r = 0.5, P = .05). The postoperative need for
      inotropes (n = 8) was associated with a low baseline CA velocity time integral at
      1 hour (r = 0.52, P < .05), low LVO at 1 and 8 hours (P < .05), and increased
      oxygen requirement at 24 hours (P < .05). CONCLUSIONS: PDA ligation is followed
      by altered CA perfusion. Perioperative evaluation of the CA perfusion can help
      identify neonates at risk of impaired myocardial performance, systolic
      hypotension, and the need for inotropes.

PMID- 22153860
TI  - Nanocoating with titanium reduces iC3b- and granulocyte-activating immune
      response against glutaraldehyde-fixed bovine pericardium: a new technique to
      improve biologic heart valve prosthesis durability?
AB  - OBJECTIVES: An IgG and granulocyte-activating immune response with secondary
      dystrophic calcification might be the reason glutaraldehyde (GA)-fixed xenograft
      valves fail, especially in young patients, who are more immunocompetent than the
      elderly. Titanium nanocoating on GA-fixed bovine pericardium was tested for its
      ability to prevent major immunoreactions. METHODS: The immune activity of
      platelets from GA-fixed bovine pericardium with different treatment procedures
      was evaluated using the blood from 5 human donors: group I (n = 5), GA fixed as
      the control; group 2 (n = 5), detoxified with 10% citric acid; group 3 (n = 5),
      10% citric acid, aldehyde-dehydrogenase, and a physical plasma treatment; and
      group 4 (n = 5), treated the same as group 3, but with an additional titanium
      coat 30 nm in thickness. Titanium deposition was visualized using scanning
      electron microscopy. IgG deposits (iC3b) were shown by immunostaining and
      documented as colored pixels (red). The pixels were evaluated electronically.
      Attracted granulocytes (polymorphonuclear leukocytes) were counted in front of
      the titanium-coated surface. RESULTS: IC3b deposits and polymorphonuclear
      leukocytes within control group 1 were defined as 100%; in group 2, iC3b was 149%
      +/- 34% and polymorphonuclear leukocytes were 89%, in group 3, IC3b was 102% +/-
      24% and polymorphonuclear leukocytes were 47%; and in group 4, IC3b had decreased
      to 38.49% +/- 21% (P < .05) and polymorphonuclear leukocyte activation had
      decreased to 6.3% (P <= .01). CONCLUSIONS: Titanium coating significantly reduced
      the iC3b and granulocyte activating immune response of GA-fixed pericardium.
      Therefore, it might prevent relevant immunorejection and increase the durability
      of GA-fixed bioprosthetic heart valves.

PMID- 22153861
TI  - A-1048400 is a novel, orally active, state-dependent neuronal calcium channel
      blocker that produces dose-dependent antinociception without altering hemodynamic
      function in rats.
AB  - Blockade of voltage-gated Ca2+ channels on sensory nerves attenuates
      neurotransmitter release and membrane hyperexcitability associated with chronic
      pain states. Identification of small molecule Ca2+ channel blockers that produce
      significant antinociception in the absence of deleterious hemodynamic effects has
      been challenging. In this report, two novel structurally related compounds, A
      686085 and A-1048400, were identified that potently block N-type (IC50=0.8 MUM
      and 1.4 MUM, respectively) and T-type (IC50=4.6 MUM and 1.2 MUM, respectively)
      Ca2+ channels in FLIPR based Ca2+ flux assays. A-686085 also potently blocked L
      type Ca2+ channels (EC50=0.6 MUM), however, A-1048400 was much less active in
      blocking this channel (EC50=28 MUM). Both compounds dose-dependently reversed
      tactile allodynia in a model of capsaicin-induced secondary hypersensitivity with
      similar potencies (EC50=300-365 ng/ml). However, A-686085 produced dose-related
      decreases in mean arterial pressure at antinociceptive plasma concentrations in
      the rat, while A-1048400 did not significantly alter hemodynamic function at
      supra-efficacious plasma concentrations. Electrophysiological studies
      demonstrated that A-1048400 blocks native N- and T-type Ca2+ currents in rat
      dorsal root ganglion neurons (IC50=3.0 MUM and 1.6 MUM, respectively) in a
      voltage-dependent fashion. In other experimental pain models, A-1048400 dose
      dependently attenuated nociceptive, neuropathic and inflammatory pain at doses
      that did not alter psychomotor or hemodynamic function. The identification of A
      1048400 provides further evidence that voltage-dependent inhibition of neuronal
      Ca2+ channels coupled with pharmacological selectivity vs. L-type Ca2+ channels
      can provide robust antinociception in the absence of deleterious effects on
      hemodynamic or psychomotor function.

PMID- 22153862
TI  - Canaries in a coalmine: Immigration and overweight among Mexican-origin children
      in the US and Mexico.
AB  - The prevalence of overweight is higher for Hispanic children of immigrants than
      children of natives. This does not fit the pattern of the epidemiological
      paradox, the widely supported finding that immigrants tend to be healthier than
      their U.S.-born peers, and it suggests that exposure to the U.S. increases
      immigrant children's risk of overweight. This study's primary contribution is to
      better assess how exposure to the U.S. environment affects childhood overweight
      among a homogamous ethnic group, Mexican-Americans. We do so by using an
      innovative binational study design to compare the weight of Mexican-American
      children of immigrants, Mexican-American children of natives, and Mexican
      children in Mexico with different propensities of having immigrant parents. Cross
      sectional data are derived from a pooled sample of 9982 6-19 year old children
      living in either Mexico or the United States in the early 2000s. Mexican-resident
      children with a very high propensity to have immigrant parents have significantly
      lower percentile BMIs and lower odds of overweight than Mexican children with
      lower propensities of emigration and U.S.-resident Mexican-American children.
      This suggests that selection into immigration streams does not account for the
      high prevalence of overweight among children of Mexican immigrants. Rather, U.S.
      exposure significantly raises children of Mexican immigrants' risk of being
      overweight. Moreover, second generation children have the highest percentile BMIs
      and greatest odds of overweight of all comparison groups, including children of
      natives. This suggests that they experience risks above and beyond the effects of
      exposure to American society.

PMID- 22153863
TI  - The role of TNF and Fas dependent signaling in animal models of inflammatory
      liver injury and liver cancer.
AB  - Tumor Necrosis Factor (TNF) alpha is a pleiotropic cytokine triggering either pro
      inflammatory effects via NF-kappaB related pathways or apoptosis through
      activation of caspase-8. The related death ligands Fas and TRAIL use homologous
      receptors and similar signaling cascades but predominantly induce apoptosis.
      Here, we summarize our experimental approaches to analyze the mechanisms and
      consequences of TNF and Fas signaling with the ultimate aim to define molecular
      targets for the treatment of inflammatory liver disease and liver cancer. By
      using conditional knockout technology in mice we genetically dissected the I
      kappa B kinase (IKK) complex consisting of IKK1/IKKalpha, IKK2/IKKbeta and
      IKKgamma/NEMO. We demonstrated that IKK2/IKKbeta, but not IKKgamma/NEMO might be
      a promising target for the prevention of liver injury after ischemia and
      reperfusion or treating steatohepatitis. Genetic inactivation of IKKgamma/NEMO
      defined a new animal model of spontaneous hepatitis and hepatocarcinogenesis
      involving constitutive activation of caspase-8 and basal apoptosis. We further
      show that caspase-8 is not only regulated by post-translational modifications as
      suggested earlier, but also by complex transcriptional regulation. Targeted
      stimulation of the caspase-8 promoter by interferons alpha and gamma, cytotoxic
      drugs or p53 can substantially sensitize hepatoma cells for apoptosis, whereas
      hepatocellular carcinoma frequently present an inactive caspase-8 gene promoter.
      In conclusion, our work demonstrates that therapeutic intervention in the TNF-NF
      kappaB-caspase-8 network is technically feasible and could be of potential
      benefit in inflammatory liver disease.

PMID- 22153864
TI  - Randomized trial of pterygium surgery with mitomycin C application using
      conjunctival autograft versus conjunctival-limbal autograft.
AB  - PURPOSE: To compare the outcomes of free conjunctival autograft (CAU) versus
      conjunctival-limbal autograft (CLAU) in the prevention of recurrence after
      pterygium surgery with adjunctive mitomycin C application in patients with
      primary or recurrent pterygia. DESIGN: Prospective, randomized study.
      PARTICIPANTS AND CONTROLS: Eighty-seven eyes of 86 patients with primary or
      recurrent nasal pterygia were included. METHODS: All eyes underwent pterygium
      excision followed by removal of subconjunctival fibrovascular tissue and
      application of 0.02% mitomycin C for 3 minutes. The eyes then were assigned
      randomly to receive either CAU (44 eyes) or CLAU (43 eyes). MAIN OUTCOME
      MEASURES: Rate of conjunctival or corneal recurrence of pterygium after surgery.
      RESULTS: A follow-up of at least 12 months (mean, 14 +/- 2.2 months) was achieved
      in 78 eyes of 78 patients, including 39 eyes in the CAU group (31 primary and 8
      recurrent pterygia) and 39 eyes in the CLAU group (33 primary and 6 recurrent
      pterygia). After surgery, no eye in the CLAU group developed pterygium
      recurrence; however, recurrence was seen in 2 eyes (5.1%) in the CAU group,
      including 1 of 31 patients (3.2%) with primary pterygia and 1 of 8 patients
      (12.5%) with recurrent pterygia. There was no statistically significant
      difference in recurrence rates between the 2 groups or in the primary and
      recurrent subgroups. In the CLAU group, a localized pannus formation at the donor
      site of the limbal graft was noted in 5 eyes (12.8%), with the appearance of
      pseudopterygium in 1 eye. CONCLUSIONS: There was no significant difference in
      recurrence rates of pterygium after surgery with mitomycin C application between
      the CAU and CLAU groups, more remarkably in primary cases. Limbal damage was seen
      in some eyes with CLAU.

PMID- 22153865
TI  - Electrostatic charge conversion processes in engineered tumor-identifying
      polypeptides for targeted chemotherapy.
AB  - One of the current challenges in cancer chemotherapy is the ultra-sensitive
      identification of in vivo tumors. Herein, we report a new class of tumor
      identifying polypeptides that can home in on in vivo tumors via an electrostatic
      charge conversion process occurring in the acidic milieu of a verity of tumors,
      which can be distinguished from receptor-interacting conventional tumor-homing
      peptides. We exploit the chemical coupling between polypeptides and therapeutic
      objects (drugs or particles) to carry out an antitumor study in nude mice, and
      find a significant increase in the efficiency of polypeptide-tagged objects in
      tumor uptake and inhibition, which is more significant than any known tumor
      homing peptide system thus far developed.

PMID- 22153866
TI  - The beneficial effects of deferred delivery on the efficiency of hydrogel therapy
      post myocardial infarction.
AB  - Biomaterials are increasingly being investigated as a means of reducing stress
      within the ventricular wall of infarcted hearts and thus attenuating pathological
      remodelling and loss of function. In this context, we have examined the influence
      of timing of delivery on the efficacy of a polyethylene glycol hydrogel
      polymerised with an enzymatically degradable peptide sequence. Delivery of the
      hydrogel immediately after infarct induction resulted in no observable
      improvements, but a delay of one week in delivery resulted in significant
      increases in scar thickness and fractional shortening, as well as reduction in
      end-systolic diameter against saline controls and immediately injected hydrogel
      at both 2 and 4 weeks post-infarction (p < 0.05). Hydrogels injected at one week
      were degraded significantly slower than those injected immediately and this may
      have played a role in the differing outcomes. The hydrogel assumed markedly
      different morphologies at the two time points having either a fibrillar or bulky
      appearance after injection immediately or one week post-infarction respectively.
      We argue that the different morphologies result from infarction induced changes
      in the cardiac structure and influence the degradability of the injectates. The
      results indicate that timing of delivery is important and that very early time
      points may not be beneficial.

PMID- 22153867
TI  - Suppression of tumor growth in H-ras12V liver cancer mice by delivery of
      programmed cell death protein 4 using galactosylated poly(ethylene glycol)
      chitosan-graft-spermine.
AB  - Non-viral gene delivery systems based on polyethyleneimine (PEI) are efficient
      due to their proton-sponge effect within endosomes, but they have poor physical
      characteristics such as slow dissociation, cytotoxicity, and non targeted gene
      delivery. To overcome many of the problems associated with PEI, we synthesized a
      galactosylated poly(ethylene glycol)-chitosan-graft-spermine (GPCS) copolymer
      with low cytotoxicity and optimal gene delivery to hepatocytes using an amide
      bond between galactosylated poly(ethylene glycol) and chitosan-graft-spermine.
      The GPCS copolymer formed complexes with plasmid DNA, and the GPCS/DNA complexes
      had well-formed spherical shapes. The GPCS/DNA complexes were nanoscale size with
      homogenous size distribution and a positive zeta potential by dynamic light
      scattering (DLS). The GPCS copolymer had lower cytotoxicity than that of PEI 25K
      in HepG2, HeLa, and A549 cell lines at various concentrations and showed good
      hepatocyte-targeting ability. Furthermore, GPCS/DNA complexes showed higher
      levels of GFP expression in the liver in model mice after intravenous injection
      than naked DNA and metoxy-poly(ethylene glycol)-chitosan-graft-spermine as
      controls without remarkable fibrosis, inflammation, lipidosis, or necrosis. In a
      tumor suppression study, an intravenous injection of the GPCS/Pdcd4 complexes
      significantly suppressed tumor growth, activated apoptosis, and suppressed
      proliferation and angiogenesis in liver tumor-bearing H-ras12V mice. Our results
      indicate that the GPCS copolymer has potential as a hepatocyte-targeting gene
      carrier.

PMID- 22153868
TI  - Mimicking the human smell sensing mechanism with an artificial nose platform.
AB  - Sensing smell is a highly complex biological process, and characterizing and
      mimicking the interaction between the olfactory receptor (OR) protein and its
      ligands is extremely challenging. Herein, we report a highly sensitive and
      selective human nose-like nanobioelectronic nose (nbe-nose), which responds to
      gaseous odorants sensitively and selectively, has a signal specificity pattern
      similar to that in the cellular signal transduction pathway, and maintains an
      antagonistic behavior similar to the human nose. The human olfaction mechanism
      was mimicked by using carboxylated polypyrrole nanotubes (CPNTs) functionalized
      with human OR protein. The nbe-nose was able to detect gaseous odorants at a
      concentration as low as 0.02 parts-per-trillion (ppt), which was comparable to a
      highly trained, human expert's nose. The nbe-nose can be used scientifically for
      smell mechanism studies. It can be also applied to various fields that rely on
      smell monitoring for industrial and public purposes.

PMID- 22153869
TI  - Quantitative control of targeting effect of anticancer drugs formulated by ligand
      conjugated nanoparticles of biodegradable copolymer blend.
AB  - There have been two strategies developed in the recent literature for
      quantitative control of the targeting effects for drug delivery by ligand
      conjugated nanoparticles of biodegradable copolymer blend such as PLGA/PLGA-PEG,
      i.e. the pre-conjugation strategy and the post-conjugation strategy, in which the
      ligand conjugation was made before and after the nanoparticle formulation
      respectively. This research developed another drug delivery system of the PLA
      TPGS/TPGS-COOH copolymer blend and further improved the post-conjugation strategy
      to precisely control the targeting effects by two ways: one is to adjust the PLA
      TPGS:TPGS-COOH copolymer blend ratio in the nanoparticle formulation process,
      which provides a way for coarse control, and another is to control the feeding
      concentration of the ligand in the herceptin conjugation process, which further
      provides a fine control. Herceptin conjugation was visualized by the FETEM with
      immumogold labeling and further quantified by the two techniques, i.e. the
      Bradford assay and the flow cytometry to confirm each other. The positive
      correlation between the surface density of the ligand and the cellular
      internalization as well as the cytotoxicity of the nanoparticle formulations was
      assessed, which demonstrated that the strategy developed in this research is
      simple and feasible, which can precisely control the targeting effects of the
      nanoparticles of biodegradable polymers as well as other nanocarriers such as
      micelles and liposomes.

PMID- 22153870
TI  - The influence of spheroid formation of human adipose-derived stem cells on
      chitosan films on stemness and differentiation capabilities.
AB  - Adipose-derived stem cells (ASCs) have valuable applications in regenerative
      medicine, but maintaining the stemness of ASCs during in vitro culture is still a
      challenging issue. In this study, human ASCs spontaneously formed three
      dimensional spheroids on chitosan films. Most ASCs within the spheroid were
      viable, and the cells produced more extracellular molecules, like laminin and
      fibronectin. Comparing to monolayer culture, ASC spheroids also exhibited
      enhanced cell survival in serum deprivation condition. Although cell
      proliferation was inhibited in spheroids, ASCs readily migrated out and
      proliferated upon transferring spheroids to another adherent growth surface.
      Moreover, spheroid-derived ASCs exhibited higher expansion efficiency and colony
      forming activity. Importantly, we demonstrated that spheroid formation of human
      ASCs on chitosan films induced significant upregulation of pluripotency marker
      genes (Sox-2, Oct-4 and Nanog). By culturing the ASC spheroids in proper
      induction media, we found that ASC differentiation capabilities were
      significantly enhanced after spheroid formation, including increased
      transdifferentiation efficiency into neuron and hepatocyte-like cells. In a nude
      mice model, we further showed a significantly higher cellular retention ratio of
      ASC spheroids after intramuscular injection of spheroids and dissociated ASCs.
      These results suggested that ASCs cultured as spheroids on chitosan films can
      increase their therapeutic potentials.

PMID- 22153871
TI  - Biological effects of alpha particle radiation exposure on human monocytic cells.
AB  - Radon ((222)Rn) gas produces decay progeny that emits high energy alpha (alpha)
      particles. Epidemiological studies have shown that exposure to (222)Rn is linked
      with elevated risk of developing lung cancer, however clear mechanisms leading to
      such effects have not been delineated. Cytokines play a critical role in
      inflammation and their dysregulated production often contributes to disease
      pathogenesis. In this study, Bio-plex multiplex technology was employed to
      investigate modulations of 27 pro-inflammatory cytokines following exposure of
      human monocytic cells to 1.5 Gy of alpha-particle radiation. Concurrently, DNA
      damage was assessed by examining the formation of phosphorylated H2A histone
      family X (gamma-H2AX) sites. Of the 27 cytokines assessed, 4 cytokines were shown
      to be statistically downregulated by ~2 fold relative to the untreated controls
      and included the interleukin (IL) family of proteins (IL-2, IL-15 and IL-17) and
      macrophage inflammatory protein 1 beta (MIP-1b). Interferon-inducible protein-12
      (IP-12), vascular endothelial growth factor and regulated on activation normal T
      cell expressed and secreted (RANTES) were shown to be high expressors and
      upregulated. Cells irradiated with alpha-particles ranging from 0.27 to 2.14 Gy
      showed statistically significant, dose-dependant increases in gamma-H2AX
      formation. These data suggest that alpha-particle radiation causes dysregulation
      in the production of a number of pro-inflammatory cytokines and results in
      significant DNA damage.

PMID- 22153872
TI  - Synthesis of novel 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic
      compounds and their evaluation for tuberculostatic activity.
AB  - A series of novel 3-cyclohexylpropanoic acid derivatives and 3
      cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds (1-8) have been
      synthesized and evaluated for tuberculostatic activity. Compounds 1a, 1c, 1e and
      1f bearing benzimidazole or benzimidazole-like systems showed the most potent
      tuberculostatic activity against Mycobacterium tuberculosis strains with MIC
      values ranging from 1.5 to 12.5MUg/mL. More importantly 1a (6-chloro-2-(2
      cyclohexylethyl)-4-nitro-1H-benzo[d]imidazole) and 1f (2-(2-cyclohexylethyl)-1H
      imidazo[4,5-b]phenazine) appeared selective for M. tuberculosis as compared with
      eukaryotic cells (human fibroblasts), and other antimicrobial strains. These
      compounds may thus represent a novel, selective class of antitubercular agents.
      Additionally compound 1a stimulated type I collagen output by fibroblasts, in
      vitro.

PMID- 22153873
TI  - Persipeptides A and B, two cyclic peptides from Streptomyces sp. UTMC 1154.
AB  - Two new N-methylated cyclopeptides, persipeptide A (1) and B (2), have been
      isolated from Streptomyces sp. UTMC1154. Their structures were established using
      1D and 2D NMR experiments. 2D TOCSY experiments were applied to identify the
      amino acid residues, while HMBC correlations were used to determine their
      sequence. According to Marfey's method, all amino acids had the l-configuration.
      The two cyclic peptides had the same ring size and amino acid composition, but
      differed in their sequence; they did not show activity against the tested
      bacteria, fungi and algae. Molecular identification experiments placed the strain
      in the genus Streptomyces closely related to Streptomyces coerulescens
      DSM40146(T) (99.45%) and Streptomyces varsoviensis DSM40346(T) (99.25%).

PMID- 22153874
TI  - Marine sponge Hymeniacidon sp. amphilectane metabolites potently inhibit rat
      brain microglia thromboxane B2 generation.
AB  - The effects of five Hymeniacidon sp. amphilectane metabolites (1-5) and two semi
      synthetic analogs (6 and 7) on thromboxane B(2) (TXB(2)) and superoxide anion
      (O(2)(-)) generation from Escherichia coli LPS-activated rat brain microglia were
      investigated. All Hymeniacidon sp. metabolites and analogs potently inhibited
      TXB(2) (IC(50)=0.20-4.69MUM) with low lactate dehydrogenase release and minimal
      mitochondrial dehydrogenase inhibition. While a lack of O(2)(-) inhibition would
      suggest that Hymeniacidon sp. metabolites and derivatives inhibit TXB(2)
      synthesis by a cyclooxygenase-dependent mechanism, their pharmacologic potency
      and limited in vitro cytotoxicity warrants further investigation to develop them
      as lead compounds to modulate enhanced TBX(2) release by activated microglia in
      neuroinflammatory disorders.

PMID- 22153875
TI  - Strategies for training in diagnostic upper endoscopy: a prospective, randomized
      trial.
AB  - BACKGROUND: Training simulators have been used for decades with success; however,
      a standardized educational strategy for diagnostic EGD is still lacking.
      OBJECTIVE: Development of a training strategy for diagnostic upper endoscopy.
      STUDY DESIGN: Prospective, randomized trial. SETTINGS: A total of 28 medical and
      surgical residents without endoscopic experience were enrolled. Basic skills
      evaluations were performed following a structured program involving theoretical
      lectures and a hands-on course in diagnostic EGD. Subsequently, stratified
      randomization to clinical plus simulator training (group 1, n = 10), clinical
      training only (group 2, n = 9), or simulator training only (group 3, n = 9) was
      performed. Ten sessions of simulator training were conducted for groups 1 and 3
      during the 4-month program. Group 2 underwent standard training in endoscopy
      without supplemental simulator training. The final evaluation was performed on
      the simulator and by observation of 3 clinical cases. Skills and procedural times
      were recorded by blinded and unblinded evaluators. MAIN OUTCOME MEASUREMENTS:
      Time to reach the duodenum, pylorus, or esophagus. RESULTS: All trainees
      demonstrated a significant reduction in procedure time during a simple manual
      skills test (P < .05) and significantly better skills scores (P = .006, P = .042
      and P = .017) in the simulator independent of the training strategy. Group 1
      showed shorter times to intubate the esophagus (61 +/- 26 seconds vs 85 +/- 30
      seconds and 95 +/- 36 seconds) and the pylorus (183 +/- 65 seconds vs 207 +/- 61
      seconds and 247 +/- 66 seconds) during the clinical evaluation. Blinded
      assessment of EGD skills showed significantly better results for group 1 compared
      with group 3. Blinded and unblinded evaluations were not statistically different.
      LIMITATIONS: Small sample size. CONCLUSIONS: Structured simulator training
      supplementing clinical training in upper endoscopy appears to be superior to
      clinical training alone. Simulator training alone does not seem to be sufficient
      to improve endoscopic skills.

PMID- 22153876
TI  - Eyelid myoclonia with absences occurring during the clinical course of
      cryptogenic myoclonic epilepsy of early childhood.
AB  - We describe a 15-year-old boy with learning difficulties and eyelid myoclonia
      with absences (EMA). Myoclonic jerks of the extremities and trunk occurred 9
      years before the onset of EMA, when the patient was 6. At that time, we diagnosed
      him with cryptogenic myoclonic epilepsy of early childhood, because he manifested
      mainly myoclonic jerks with generalized 3- to 6-Hz spike/polyspike-and-slow-wave
      complexes on EEG, normal neurological examination, good response to antiepileptic
      drugs, and no evidence of previous brain damage. This is an unusual case showing
      that myoclonic epilepsy of early childhood can evolve to EMA. Although the
      question of whether EMA is a seizure type or an epilepsy syndrome remains
      controversial, our case suggests that EMA is a seizure type during the clinical
      course of a particular kind of myoclonic epilepsy.

PMID- 22153877
TI  - Human and environmental biomonitoring of polychlorinated biphenyls and
      hexachlorobenzene in Saxony, Germany based on the German Environmental Specimen
      Bank.
AB  - The objective of the present study was to investigate the principle relationships
      between concentrations in human and environmental matrices of polychlorinated
      biphenyls (PCBs) and hexachlorobenzene (HCB) in short distance comparable areas
      within Saxony, Germany by employing the data of the German Environmental Specimen
      Banking (ESB). Examples supporting this idea were presented by selecting data on
      blood plasma collected from students in University of Halle and pine shoots, egg
      matter of city pigeons, earthworm, and roe deer liver. Similar pattern for PCB
      138 and PCB 180 was found for the human plasma and pine shoots samples during
      investigated years and the human data followed the corresponding environmental
      levels with some delay of approximately two years. However, PCB 153 that was the
      prevailing congener did not manifest this relationship. In addition, the
      correlation of the ratios of concentrations (human/environmental concentration)
      to some physicochemical constants such as molecular weight (MW), octanol-water
      partition coefficient (logK(ow)), Henry's law constant (K(H)), and sorption
      partition coefficient (logK(oc)) of HCB, PCB 138, PCB 153, and PCB 180 were
      studied. The resulted negative slopes with all constants in case of blood
      plasma/city pigeons egg matter pairs suggested that the accumulation of
      lipophilic compounds is more pronounced in pigeon eggs than in human blood.

PMID- 22153878
TI  - Increased serum levels of advanced oxidation protein products and glycation end
      products in subjects exposed to low-dose benzene.
AB  - Simple aromatic hydrocarbon benzene occurs naturally in crude oil and petroleum.
      Benzene has been internationally recognised as a haematotoxin and carcinogen. The
      involvement of oxidative stress is a major susceptibility factors for benzene
      hematotoxicity in humans. Advanced oxidation protein products (AOPPs) and
      advanced glycation end products (AGEs) are modified structures which can serve as
      markers of oxidative stress. The aim of this study is to assess modification of
      circulating AOPPs and AGEs, as early markers of oxidative stress, in subjects
      exposed to low dose of benzene. Furthermore the genetic polymorphism of
      glutathione-S-transferase (GST) may be related to health effects of benzene
      exposure, in fact both genotype T1 (GSTT1) and M1 (GSTM1) are involved in the
      detoxification of benzene oxide. The study was performed on 54 workers oil
      refinery employees. A group of 32 healthy age-matched subjects was included as
      controls. The AOPPs serum levels in oil refinery employees were higher in a
      statistically significant way than those measured in controls, but there were no
      significant changes in serum AGE levels between both groups. However, GST
      polymorphisms had not influence on serum levels of both biomarkers, so
      demonstrating that production of circulating AGEs and AOPPs in benzene parity
      exposed workers levels is not dependent by GST genotypes. We can conclude that,
      in this condition, AOPPs are more sensitive marker of low benzene exposure than
      AGEs.

PMID- 22153879
TI  - Genetic polymorphisms and surface expression of CTLA-4 and PD-1 on T cells of
      silica-exposed workers.
AB  - Exposure to silica dust has been examined as a possible risk factor for
      autoimmune diseases, including scleroderma, rheumatoid arthritis and systemic
      lupus erythematosus. Since CTLA-4 [CD152] and PD-1 [CD279] are important for the
      maintenance of peripheral tolerance by regulating T cell responsiveness, we
      evaluated the expression of these molecules on the surface of CD4 and CD8 T
      cells, as well as single nucleotide polymorphisms (SNP) in CTLA-4 and PDCD1
      genes, of 70 silica-exposed workers and 30 non-exposed, age-, ethnically- and sex
      matched controls. Expression of CTLA-4 was significantly (P<0.05) reduced in CD4
      T cells of exposed individuals [median=0.1% and interquartile range, IQR 0.0-0.1%
      (exposed), median=0.20%, IQR 0.0-0.4% (control)]. Also the expression of PD-1 was
      significantly (P<0.0001) reduced in both CD4 [median=0.9%, IQR 0.4-2.3%
      (exposed), median=5.7%, IQR 1.4-13.3% (control)] and CD8 T cells [median=0.9%,
      IQR 0.3-1.9% (exposed), median=5.0%, IQR 3.4-8.9% (control)]. The study of
      polymorphisms demonstrated a lower frequency of the A allele in the analysis of
      the PD1.3 SNP in the exposed group, which might be associated with the lower
      expression of PD-1 on the surface of CD4 T cells. Our findings provide evidence
      for the association of silica exposure and the maintenance of self-tolerance,
      i.e., the susceptibility to autoimmune disorders.

PMID- 22153881
TI  - Sex differences in disease severity among patients with systemic lupus
      erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE), a prototypical autoimmune
      disease, often results in comorbidities from exposure to medications as well as
      from chronic inflammation. Identification of gender-based differences in
      comorbidities and disease severity may assist health practitioners in providing
      optimum care for those living with SLE. OBJECTIVE: The purpose of this study,
      which utilized hospital discharge data collected during a 7-year period to garner
      a large SLE patient sample, was to determine the effect of gender on SLE
      comorbidities and disease severity. METHODS: Patients were hospitalized in the
      Dallas-Fort Worth metropolitan statistical area between 1999 and 2005 and had a
      diagnosis of SLE. The sample consisted of 14,829 patients with SLE, 10% of which
      were male. ANOVAs were conducted to test for differences between males and
      females for disease severity, age, length of stay in the hospital, total hospital
      charges, and number of autoimmune diseases. Disease severity was measured with
      the SLE comorbidity index, which weights 14 conditions in SLE. We identified the
      top 30 comorbidities as well as the odds of experiencing the secondary illnesses
      by gender. RESULTS: Male patients had significantly greater disease severity
      compared with female patients. Additionally, female patients had more autoimmune
      diagnoses compared with male patients. Male patients were more likely to have
      cardiovascular and renal comorbidities compared with female patients. Female
      patients had significantly greater odds of diagnoses of urinary tract infection,
      hypothyroidism, depression, esophageal reflux, asthma, and fibromyalgia.
      CONCLUSIONS: Although the prevalence of SLE among males is rare, male patients
      have the potential for greater disease severity and are more likely to suffer
      from cardiovascular and renal disease. Gender differences in disease severity
      should be further evaluated, but with the added recommendation to develop an
      index with conditions more indicative of active SLE.

PMID- 22153880
TI  - Evidence that the G protein-coupled membrane receptor GPR30 contributes to the
      cardiovascular actions of estrogen.
AB  - Although female protection from cardiovascular diseases declines with the fall in
      circulating sex hormones experienced during menopause, clinical trials in older
      women fail to demonstrate beneficial effects for hormone replacement therapy. The
      recent discovery of GPR30, a membrane-bound estrogen receptor that is
      structurally and functionally unique from the steroid receptors ERalpha and
      ERbeta, has unveiled additional signaling pathways by which estrogen may
      influence cardiovascular health. This review takes an organ-based approach to
      assess the expression and function of GPR30 in the cardiovascular system. We
      concluded that although the current literature does suggest a cardiovascular role
      for GPR30, additional exploration is necessary to fully elucidate the estrogenic
      actions mediated by this novel receptor.

PMID- 22153882
TI  - Women underrepresented on editorial boards of 60 major medical journals.
AB  - BACKGROUND: Although there has been a continuous increase in the number of women
      working in the field of medicine, women rarely reach the highest academic
      positions as full professors or editorial board members. OBJECTIVE: We aimed to
      determine the proportion of women on the editorial boards of top-ranked medical
      journals in different medical specialties. METHODS: We analyzed the gender of
      editorial board members of 60 top-ranked journals of 12 Thomson Reuters Web of
      Knowledge Journal Citation Reports categories. A total of 4175 editors were
      included in our analysis. RESULTS: Only 15.9% (10 of 63) editors-in-chief were
      female. In the 5 categories, critical care, anesthesiology, orthopedics,
      ophthalmology and radiology, nuclear medicine and medical imaging, currently not
      1 woman holds the position of editor-in-chief. Less than one fifth (17.5%, 719 of
      4112) of all editorial board members were women. There were significant
      differences among the evaluated categories, with the highest percentage of women
      in the category of medicine, general and internal and the lowest in the category
      critical care, followed by orthopedics. In every category, the proportion of
      women as editorial board members was substantially lower than that of men.
      CONCLUSIONS: Women are underrepresented on the editorial boards of major medical
      journals, although there is a great variability among the journals and categories
      analyzed. If more women are nominated to serve on editorial boards, they will be
      a visible sign of continuing progress and serve as important role models for
      young women contemplating a career in academic medicine.

PMID- 22153883
TI  - Ten-year change in the association between obesity and parity: results from the
      National FINRISK Population Study.
AB  - BACKGROUND: Overweight or weight development related to pregnancy has been
      associated with number of deliveries (ie, parity). OBJECTIVE: This study
      evaluates 10-year changes in associations between obesity and parity. METHODS:
      The data were from the National FINRISK Study on women 25-64 years of age. The
      study included a questionnaire and anthropometric measurements in 1997 (N = 4193)
      and 2007 (N = 3578). Women whose body mass index (BMI) was >= 30 kg/m2 were
      considered obese, and women whose waist circumference was >= 88 cm were
      considered viscerally obese. Women with no pregnancies were categorized as
      nulliparous, those with 1-2 deliveries as parous, and those with >= 3 deliveries
      as multiparous. Logistic regression models were used to estimate separately the
      odd ratios (ORs) and 95% CIs for BMI and waist circumference. Linear regression
      models were used to evaluate the main effect of parity on obesity and visceral
      obesity. RESULTS: Women with 1 or 2 children were less often obese (OR = 0.75;
      95% CI, 0.64-0.88) or viscerally obese (OR = 0.98; 95% CI, 0.85-1.14) than
      nulliparous or multiparous women. Multiparous women had more visceral obesity in
      2007 (OR = 1.36; 95% CI, 1.16-1.60) than other parity groups. Multiparous women
      had the highest BMI or waist circumference even after adjusting for age, study
      year, and education. The year 2007 was significantly associated with visceral
      obesity (OR = 2.07; 95% CI, 1.87-2.30) and obesity (OR = 1.13; 95% CI, 1.01-1.28)
      when compared with 1997. CONCLUSION: Parity is an important determinant of
      visceral obesity, which is more prevalent in younger age groups than a decade
      ago. Women with >= 3 deliveries were more often obese or viscerally obese than
      other women.

PMID- 22153884
TI  - Prometheus and the heaven scenario: progress and challenges in 21st century
      science.

PMID- 22153885
TI  - 2012 ACCF/AHA/ACR/SCAI/SIR/STS/SVM/SVN/SVS Key data elements and definitions for
      peripheral atherosclerotic vascular disease: a report of the American College of
      Cardiology Foundation/American Heart Association Task Force on Clinical Data
      Standards (Writing Committee to develop Clinical Data Standards for peripheral
      atherosclerotic vascular disease).

PMID- 22153886
TI  - Variation, precision and validity of 1-year survival estimates for lung, breast,
      colon and prostate cancer in South East England primary care trusts.
AB  - BACKGROUND: English cancer policy has encouraged primary care trusts (PCTs) to
      consider their 1-year cancer survival estimates. This study quantifies variation
      in these estimates across 39 PCTs in the London and South East Coast strategic
      health authorities, and explores their precision, possible confounding by age and
      bias due to death certificate only (DCO) registrations. STUDY DESIGN:
      Retrospective observational study. METHODS: One-year relative survival estimates
      and data on DCO registrations for patients diagnosed with lung, colorectal,
      breast and prostate cancers between 2002 and 2006 were extracted from the UK
      Cancer Information Service. Direct age standardization was performed with
      weightings derived from the standard cancer patient population for Europe.
      Pearson correlation coefficients between survival estimates and DCO proportions
      were calculated. RESULTS: Mean 1-year PCT survival estimates ranged from 6.9 to
      19.4 percentage points, and the precision of individual estimates ranged from +/
      0.9 to +/-6.5 percentage points (at 95% confidence level). Age standardization
      significantly changed the estimates of nine PCTs for breast cancer, five PCTs for
      lung cancer and three PCTs for colorectal cancer. None of the prostate cancer
      estimates were affected significantly. DCO proportions were positively associated
      with lung cancer survival and negatively associated with colorectal and breast
      cancer survival. CONCLUSIONS: PCT 1-year cancer survival estimates may be
      informative, but caveats relating to data quality and hence the validity of the
      estimates means that they require careful investigation before naive use, as
      random variation, confounding due to age and bias due to DCO registrations may be
      significant.

PMID- 22153887
TI  - Protein kinase mzeta is necessary for cocaine-induced synaptic potentiation in
      the ventral tegmental area.
AB  - BACKGROUND: Much progress has been made in our understanding of brain regions and
      specific receptors that are involved in the action of cocaine addiction. Although
      long-term modifications of mesolimbic reward circuit following cocaine exposure
      are responsible for cocaine-addicted behaviors, the underlying molecular
      mechanism at the cellular level is still obscure. Here, we investigated the
      possible participation of protein kinase Mzeta (PKMzeta) in synaptic potentiation
      following cocaine exposure. METHODS: Spontaneous and evoked synaptic activity of
      glutamate synapse in saline- and cocaine-treated rats were examined by preparing
      acute brain slices and performing whole-cell voltage-clamp recordings from
      individual dopamine neurons in the ventral tegmental area (VTA). We also assessed
      the role of PKMzeta on the behavioral responses by cocaine conditioned place
      preference. RESULTS: Chelerythrine, an inhibitor of PKMzeta, reversed the cocaine
      induced facilitation of spontaneous synaptic transmission in the VTA. PKMzeta
      inhibition by chelerythrine or myristoylated zeta inhibitory peptide
      significantly attenuated the cocaine exposure-induced enhancement of alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate
      receptor ratio. Myristoylated zeta inhibitory peptide had no effect on spike
      timing-dependent long-term potentiation in rats previously injected with saline
      but remarkably restored spike timing-dependent long-term potentiation in VTA
      dopamine neurons in slices prepared from rats that received single or multiple
      cocaine exposure. Western blot analyses showed that both single and five
      consecutive cocaine injections induced a significant increase in PKMzeta level.
      Furthermore, intracranial infusion of myristoylated zeta inhibitory peptide in
      the VTA disrupted cocaine conditioned place preference. CONCLUSIONS: Our results
      suggest that persistent activity of PKMzeta is a requisite for cocaine-induced
      enhancement of synaptic plasticity in the VTA and cocaine conditioned place
      preference.

PMID- 22153888
TI  - Cost and clinical implications of diabetes prevention in an Australian setting: a
      long-term modeling analysis.
AB  - AIMS/HYPOTHESIS: Metformin and intensive lifestyle changes (ILC) reduced the
      incidence of type 2 diabetes (T2D) versus standard care (control) in overweight
      or obese subjects with impaired glucose tolerance (IGT) in the Diabetes
      Prevention Program (DPP) trial and Diabetes Prevention Program Outcomes Study
      (DPPOS). We projected lifetime clinical and economic outcomes based on the
      results from the DPP+DPPOS, from a 3rd-party payer perspective in Australia.
      METHODS: A semi-Markov, 2nd-order Monte Carlo model was developed with four
      health states: "normal glucose regulation" (NGR); IGT; T2D and 'dead'. Outcomes
      were discounted at 5% annually. Univariate and probabilistic sensitivity analyses
      were performed. Incremental cost-effectiveness ratios (ICERs) were calculated.
      RESULTS: Cumulative incidence (standard deviation) of T2D was 89.7% (0.2), 83.8%
      (0.2) and 73.4% (0.3%) for control, metformin and ILC respectively. Lifetime
      incremental direct costs were $1217 (4411) per subject for metformin versus
      control, with cost savings of $289 (4296) for ILC versus control. ILC therefore
      dominated control, with improvements in clinical outcomes and overall cost
      savings. Incremental costs per QALY-gained for metformin versus control were
      $10,142. Probability of cost-effectiveness at willingness-to-pay threshold of
      $50,000 was 78% and 100% for metformin or ILC respectively. Results were most
      sensitive to probabilities of developing T2D and costs of implementing the
      interventions. CONCLUSIONS/INTERPRETATION: Substantial improvements in lifetime
      clinical outcomes could be expected in high risk subjects treated with metformin
      or ILC. Prevention of T2D in this group of subjects is good value for money, and
      may even lead to long term cost savings.

PMID- 22153889
TI  - Characterization of a homemade ionization chamber for radiotherapy beams.
AB  - A homemade cylindrical ionization chamber was studied for routine use in therapy
      beams of (60)Co and X-rays. Several characterization tests were performed:
      leakage current, saturation, ion collection efficiency, polarity effect,
      stability, stabilization time, chamber orientation and energy dependence. All
      results obtained were within international recommendations. Therefore the
      homemade ionization chamber presents usefulness for routine dosimetric procedures
      in radiotherapy beams.

PMID- 22153890
TI  - Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with
      locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere):
      a randomised multicentre, open-label, phase 2 trial.
AB  - BACKGROUND: Studies with pertuzumab, a novel anti-HER2 antibody, show improved
      efficacy when combined with the established HER2-directed antibody trastuzumab in
      breast cancer therapy. We investigated the combination of pertuzumab or
      trastuzumab, or both, with docetaxel and the combination of pertuzumab and
      trastuzumab without chemotherapy in the neoadjuvant setting. METHODS: In this
      multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive
      breast cancer were randomly assigned (1:1:1:1) centrally and stratified by
      operable, locally advanced, and inflammatory breast cancer, and by hormone
      receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg/kg
      loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m(2),
      escalating, if tolerated, to 100 mg/m(2) every 3 weeks; group A) or pertuzumab
      (loading dose 840 mg, followed by 420 mg every 3 weeks) and trastuzumab plus
      docetaxel (group B) or pertuzumab and trastuzumab (group C) or pertuzumab plus
      docetaxel (group D). The primary endpoint, examined in the intention-to-treat
      population, was pathological complete response in the breast. Neither patients
      nor investigators were masked to treatment. This study is registered with
      ClinicalTrials.gov, number NCT00545688. FINDINGS: Of 417 eligible patients, 107
      were randomly assigned to group A, 107 to group B, 107 to group C, and 96 to
      group D. Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a
      significantly improved pathological complete response rate (49 of 107 patients;
      45.8% [95% CI 36.1-55.7]) compared with those given trastuzumab plus docetaxel
      (group A; 31 of 107; 29.0% [20.6-38.5]; p=0.0141). 23 of 96 (24.0% [15.8-33.7])
      women given pertuzumab plus docetaxel (group D) had a pathological complete
      response, as did 18 of 107 (16.8% [10.3-25.3]) given pertuzumab and trastuzumab
      (group C). The most common adverse events of grade 3 or higher were neutropenia
      (61 of 107 women in group A, 48 of 107 in group B, one of 108 in group C, and 52
      of 94 in group D), febrile neutropenia (eight, nine, none, and seven,
      respectively), and leucopenia (13, five, none, and seven, respectively). The
      number of serious adverse events was similar in groups A, B, and D (15-20 serious
      adverse events per group in 10-17% of patients) but lower in group C (four
      serious adverse events in 4% of patients). INTERPRETATION: Patients given
      pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved
      pathological complete response rate compared with those given trastuzumab plus
      docetaxel, without substantial differences in tolerability. Pertuzumab and
      trastuzumab without chemotherapy eradicated tumours in a proportion of women and
      showed a favourable safety profile. These findings justify further exploration in
      adjuvant trials and support the neoadjuvant approach for accelerating drug
      assessment in early breast cancer. FUNDING: F Hoffmann-La Roche.

PMID- 22153891
TI  - Closing in on accurate risk prediction and disease management for patients with
      operable GIST.

PMID- 22153892
TI  - Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis
      of pooled population-based cohorts.
AB  - BACKGROUND: The risk of recurrence of gastrointestinal stromal tumour (GIST)
      after surgery needs to be estimated when considering adjuvant systemic therapy.
      We assessed prognostic factors of patients with operable GIST, to compare widely
      used risk-stratification schemes and to develop a new method for risk estimation.
      METHODS: Population-based cohorts of patients diagnosed with operable GIST, who
      were not given adjuvant therapy, were identified from the literature. Data from
      ten series and 2560 patients were pooled. Risk of tumour recurrence was
      stratified using the National Institute of Health (NIH) consensus criteria, the
      modified consensus criteria, and the Armed Forces Institute of Pathology (AFIP)
      criteria. Prognostic factors were examined using proportional hazards and non
      linear models. The results were validated in an independent centre-based cohort
      consisting of 920 patients with GIST. FINDINGS: Estimated 15-year recurrence-free
      survival (RFS) after surgery was 59.9% (95% CI 56.2-63.6); few recurrences
      occurred after the first 10 years of follow-up. Large tumour size, high mitosis
      count, non-gastric location, presence of rupture, and male sex were independent
      adverse prognostic factors. In receiver operating characteristics curve analysis
      of 10-year RFS, the NIH consensus criteria, modified consensus criteria, and AFIP
      criteria resulted in an area under the curve (AUC) of 0.79 (95% CI 0.76-0.81),
      0.78 (0.75-0.80), and 0.82 (0.80-0.85), respectively. The modified consensus
      criteria identified a single high-risk group. Since tumour size and mitosis count
      had a non-linear association with the risk of GIST recurrence, novel prognostic
      contour maps were generated using non-linear modelling of tumour size and mitosis
      count, and taking into account tumour site and rupture. The non-linear model
      accurately predicted the risk of recurrence (AUC 0.88, 0.86-0.90).
      INTERPRETATION: The risk-stratification schemes assessed identify patients who
      are likely to be cured by surgery alone. Although the modified NIH classification
      is the best criteria to identify a single high-risk group for consideration of
      adjuvant therapy, the prognostic contour maps resulting from non-linear modelling
      are appropriate for estimation of individualised outcomes. FUNDING: Academy of
      Finland, Cancer Society of Finland, Sigrid Juselius Foundation and Helsinki
      University Research Funds.

PMID- 22153893
TI  - [Techniques of anastomoses issue from vascular surgery and apply to maxillofacial
      microsurgery].
AB  - Vascular surgeons use an anastomosis technique that has proven its efficiency for
      a long time. This technique consists in an anastomosis with spatulated ended
      vessels designed with opposite obliquity. This anastomosis is closed by a
      continuous suture. Authors expose the results of this technique applied to
      microvascular surgery in facial reconstruction.

PMID- 22153894
TI  - [Vade mecum for a surgical humanitarian mission].
AB  - Humanitarian surgical missions provide cares in developing countries and in
      difficult conditions. Preparation of these missions is a mandatory step for both
      technical and human points of view. Before the departure, care must be taken to
      accomplish all the administrative (visa application, valid passport...) and the
      medical formalities (mandatory and recommended vaccinations). The aim of this
      article is to present a helpful vade mecum allowing any surgeon, especially the
      juniors, to prepare a humanitarian mission abroad.

PMID- 22153895
TI  - Endosymbionts in paramecium.
AB  - Paramecium species are extremely valuable organisms to enable experiments for the
      reestablishment of endosymbiosis. This is investigated in two different systems,
      the first with Paramecium caudatum and the endonuclear symbiotic bacterium
      Holospora species. Although most endosymbiotic bacteria cannot grow outside the
      host cell as a result of their reduced genome size, Holospora species can
      maintain their infectivity for a limited time. We found that an 89-kDa
      periplasmic protein has an important function for Holospora's invasion into the
      target nucleus, and that Holospora alters the host gene expression; the host
      thereby acquires resistance against various stresses. The second system is the
      symbiosis between P. bursaria and symbiotic Chlorella. Alga-free P. bursaria and
      the algae retain the ability to grow without a partner. Consequently,
      endosymbiosis between the aposymbiotic host cells and the symbiotic algae can be
      reestablished easily by mixing them. We now found four checkpoints for the
      reestablishment of the endosymbiosis between P. bursaria and the algae. The
      findings in the two systems provide excellent opportunities for us to elucidate
      not only infection processes but also to assess the associations leading to
      eukaryotic cell evolution. This paper summarizes recent progresses on
      reestablishment of the primary and the secondary endosymbiosis in Paramecium.

PMID- 22153896
TI  - Canine intestinal mast cell tumor with c-kit exon 8 mutation responsive to
      imatinib therapy.
AB  - A canine intestinal mast cell tumor with splenic metastasis was treated with
      imatinib. The intestinal and metastatic tumor masses markedly decreased following
      treatment although the clinical response was short lasting. A c-kit internal
      tandem duplication mutation, c.1250_1261dup, which causes an insertion of four
      amino acids in KIT, was identified in cDNA isolated from the tumor cells. The
      phosphorylation status of the mutant KIT and the effect of imatinib on its
      phosphorylation were examined using 293 cells transfected with c-kit carrying the
      c.1250_1261dup mutation. This mutation caused ligand-independent phosphorylation
      of KIT, which was suppressed by imatinib. Inhibition of constitutively activated
      mutant KIT with imatinib could underlie the tumor response in this dog.

PMID- 22153897
TI  - Dense fibrillar collagen matrices to analyse extracellular matrix receptor
      function.
AB  - AIM: The goal of this study was to understand whether dense fibrillar collagen
      matrices, with a hierarchical structure resembling native collagen matrices,
      could be useful to study collagen receptor function, in a more physiological
      context. The receptor analysed here was integrin alpha11beta1, already shown to
      be involved in cell attachment and migration on collagen-coated plastic, and also
      in contraction of loose fibrillar collagen hydrogels. MATERIALS AND METHODS:
      Collagen matrices prepared here corresponded to dense fibrillar hydrogels
      concentrated at 5mg/ml. The behaviour of alpha11beta1 deficient fibroblasts
      seeded on these concentrated matrices was assessed in terms of adhesion,
      morphology and migration, then compared to that observed on classical hydrogels
      at 1mg/ml, corresponding to loose collagen matrices. RESULTS: Short-term
      attachment assays showed disturbed interactions between alpha11beta1 deficient
      cells and collagen matrices in a concentration-dependent manner. Long-term assays
      revealed reduced cell spreading of alpha 11(-/-) cells on the dense collagen
      matrices, associated with a disturbed cytoskeleton network. Moreover, anoikis was
      observed when alpha 11(-/-) cells were seeded on 5mg/ml matrices, and not on
      looser 1mg/ml matrices. In scratch wound in vitro assays, carried out with cells
      on 5mg/ml fibrillar collagen matrices, alpha 11(-/-) cells migrated much better
      than their wild-type counterparts. In contrast, no significant difference was
      observed between wild and knock-out cells seeded on plastic. CONCLUSIONS: The
      present study demonstrates the validity of in vivo-like dense fibrillar collagen
      matrices to evaluate cell receptor functions more significantly than with 2D cell
      cultures or loose hydrogels.

PMID- 22153898
TI  - Functional characterization of the apple MhGAI1 gene through ectopic expression
      and grafting experiments in tomatoes.
AB  - DELLA proteins are essential components of GA signal transduction. MhGAI1 was
      isolated from the tea crabapple (Malus hupehensis Redh. var. pingyiensis), and it
      was found to encode a DELLA protein. Mhgai1 is a GA-insensitive allele that was
      artificially generated via a bridge-PCR approach. Ectopic expression of Mhgai1
      reduced plant stature, decreased spontaneous fruit-set-ratio and enhanced drought
      tolerance in transgenic tomatoes. In addition, we examined the long-distance
      movement of Mhgai1 mRNAs by grafting experiments and SqRT-PCR analysis. It was
      found that the wild-type scions accumulated Mhgai1 transcripts trafficked from
      the transgenic rootstocks and therefore exhibited dwarf phenotypes. Furthermore,
      transgenic tomato plants produced more soluble solids, sugars and organic acids
      compared to wild-type tomatoes, suggesting an involvement of GA signaling in the
      regulation of fruit quality. Despite noticeable accumulation in the leaves and
      stems of WT scions, Mhgai1 transcripts were undetectable in flowers and fruit.
      Therefore, fruit quality was less influenced by the grafting of WT scions onto
      transgenic rootstocks than they were by the ectopic expression of Mhgai1 in
      transgenic rootstocks. Taken together, MhGAI1, which functions as a repressor in
      the GA signaling pathway, and its GA-insensitive allele, Mhgai1, could turn out
      to be useful targets for the genetic improvement of dwarfing rootstocks in
      apples.

PMID- 22153899
TI  - Changes in practice task constraints shape decision-making behaviours of team
      games players.
AB  - OBJECTIVES: This study examined the effects of manipulating relative positioning
      between defenders (initial distance apart) on emergent decision-making and
      actions in a 1 vs. 2 rugby union performance sub-phase. DESIGN: Twelve
      experienced youth players performed 80 trials of a 1 (attacker) vs. 2 (defenders)
      practice task in which the starting distance between defenders was systematically
      decreased. METHODS: Movement displacement trajectories of participants were video
      recorded to obtain 2D positional data. The independent variable was the starting
      distance between defenders and dependent variables were: (i) performance outcome
      (try or tackle), (ii) mean speed of all players during performance, and (iii),
      time between the first crossover and the end of the trial. Repeated measures
      ANOVA was used to compare the effects of different starting distances on
      performance. RESULTS: Shorter starting distances between defenders were
      associated with a higher frequency of effective tackle outcomes, lower mean
      speeds of all participants, and a greater time period between the first crossover
      and the end of the trial. CONCLUSIONS: Decision-making behaviours emerged as a
      function of changes in participants' spatial location during performance. This
      observation supports the importance of manipulating key spatial-temporal
      variables in designing representative practice task constraints that induce
      functional player-environment interactions in team sports training.

PMID- 22153900
TI  - Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation
      in a Turkish family with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a genetically complex disorder for which the definite
      diagnosis is only accomplished postmortem. Mutations in 3 genes (APP, PSEN1, and
      PSEN2) are known to cause AD, but a large number of familial cases do not harbor
      mutations in these genes and several unidentified genes that contain disease
      causing mutations are thought to exist. We performed whole exome sequencing in a
      Turkish patient clinically diagnosed with Alzheimer's disease from a
      consanguineous family with a complex history of neurological and immunological
      disorders and identified a mutation in NOTCH3 (p.R1231C), previously described as
      causing cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL). Complete screening of NOTCH3 in a cohort of 95
      early onset AD cases and 95 controls did not reveal any additional pathogenic
      mutations. Although the complex history of disease in this family precluded us to
      establish segregation of the mutation found with disease, our results show that
      exome sequencing is a rapid, cost-effective and comprehensive tool to detect
      genetic mutations, allowing for the identification of unexpected genetic causes
      of clinical phenotypes. As etiological based therapeutics become more common,
      this method will be key in diagnosing and treating disease.

PMID- 22153901
TI  - [Hypocalcemia as a reversible cause of heart failure].
AB  - Calcium plays a key role in heart muscle contraction and relaxation. Hypocalcemic
      heart failure is a rare and potentially reversible disturbance, which reflects
      this intrinsic relationship. The authors present the case of a 35-year-old woman
      who developed acute heart failure during the early postoperative period following
      total thyroidectomy. The echocardiogram showed severe global left ventricular
      dysfunction. Laboratory tests showed severe hypocalcemia and new-onset
      hypoparathyroidism. Cardiac catheterization showed angiographically normal
      coronary arteries. After clinical, hemodynamic and metabolic stabilization, a
      repeat echocardiogram revealed recovery of left ventricular function.
      Subsequently, cardiac magnetic resonance imaging was performed, which also showed
      no alterations. The patient was discharged asymptomatic, medicated with calcium
      carbonate, calcitriol and levothyroxine. This case highlights the importance of
      considering hypocalcemia as a cause of reversible myocardial dysfunction.

PMID- 22153902
TI  - Almanac 2011: cardiac arrhythmias and pacing. The national society journals
      present selected research that has driven recent advances in clinical cardiology.

PMID- 22153903
TI  - [Incidental cardiac findings on cardiac CT with prognostic impact].

PMID- 22153904
TI  - Local excision of uterine adenomyomas: a report of 86 cases with follow-up
      analyses.
AB  - OBJECTIVE: To assess the outcomes of patients who underwent local excision of
      adenomyoma and to evaluate the effectiveness of the procedure. STUDY DESIGN:
      Prospective study of 86 women undergoing local excision of symptomatic uterine
      adenomyoma at laparotomy. Dysmenorrhea was assessed before and after operation by
      questionnaire, and the average duration of follow-up was 24 months. RESULT(S): At
      6-month follow-up, all 86 patients' dysmenorrhea grades were reduced by more than
      80%. With a mean follow-up of 24 (range 6-60) months, a total of 2 (2.3%)
      patients finally underwent hysterectomy, 1 (1.2%) received levonorgestrel
      releasing intrauterine device therapy, and three patients (11.3%) were
      subsequently given treatment with oral pain medication alone. The mean time
      interval between local excision and subsequent treatment was 34 months. Two
      (2.3%) patients became pregnant after the local excision: one (1.2%) at 2 months
      after the procedure and one (1.2%) at 3 years after the local excision procedure.
      CONCLUSION(S): Local excision of uterine adenomyoma remains a safe and effective
      minimally invasive treatment for women with symptomatic uterine adenomyoma. Local
      excision can effectively alleviate the dysmenorrhea of adenomyoma.

PMID- 22153905
TI  - Caesarean scar pregnancy: comparative efficacy and safety of treatment by uterine
      artery chemoembolization and systemic methotrexate injection.
AB  - OBJECTIVES: The aim of this study was to investigate the efficacy and safety of
      uterine artery embolization (UAE) combined with intra-arterial methotrexate (MTX)
      infusion for the treatment of caesarean scar pregnancy (CSP), compared with
      systemic MTX injection combined with uterine curettage. STUDY DESIGN: A
      retrospective cohort study. An analysis of CSP patients was performed using
      records from the Department of Obstetrics and Gynecology in Renji Hospital for
      the period between January 1, 2000 and December 30, 2010. Twenty-two patients
      received UAE combined with intra-arterial MTX infusion and in this group 16
      patients received uterine curettage after UAE, whereas 25 patients received
      intramuscular MTX injection and subsequent uterine curettage. The clinical
      information on these patients and clinical outcomes were reviewed. RESULTS: All
      patients in the UAE group were treated successfully and 2 patients in the non-UAE
      group had to undergo hysterectomy or uterine repair. No patients in the UAE group
      had recurrent vaginal bleeding of more than 100ml/day after treatment, while 8
      patients in the non-UAE group did, and this difference was significant. The blood
      loss during uterine curettage in the UAE group was much less than in non-UAE
      group. The serum beta-hCG level in the UAE group recovered more quickly than in
      the non-UAE group, and hospital stay was significantly shorter in the UAE group.
      CONCLUSIONS: UAE combined with intraarterial MTX infusion turned out to be an
      effective and safe treatment for CSP.

PMID- 22153906
TI  - Combined intraperitoneal instillation and port site infiltration of local
      anaesthetic (bupivacaine) for postoperative analgesia in women undergoing daycare
      diagnostic gynaecological laparoscopy.

PMID- 22153907
TI  - Predicting summer hypoxia in the northern Gulf of Mexico: redux.
AB  - We report on the evolution and accuracy of a model used to predict the mid-summer
      area of hypoxia (oxygen <=2 mg l(-1)) in the northern Gulf of Mexico, use it to
      test for impacts from the Deepwater Horizon oil spill (2010), and estimate the N
      loading that would meet a management goal. The prediction since 2000 were 100%+/
      6% (MU+/-1 SE) of the actual value. The predicted in 2010 was 99% of that actual
      value, suggesting that the net effect of the 2010 oil spill on the hypoxic zone
      size was negligible. A tropical storm, however, may have reduced the potential
      size of the hypoxic zone. Lowering the May nitrogen load to about 70,000 mton N
      nitrate+nitrite would bring the model's predicted hypoxic zone size down to the
      management goal of 5000 km(2) and restore hypoxic waters to normoxic conditions.

PMID- 22153908
TI  - Links between bacterial communities in marine sediments and trace metal
      geochemistry as measured by in situ DET/DGT approaches.
AB  - Our current view about the relationship between metals and bacteria in marine
      sediments might be biased because most studies only use ex situ approaches to
      quantify metals. The aim of the present research was to compare ex situ and in
      situ methods of metal measurement (DET and DGT--diffusive equilibration or
      diffusive gradients in thin-films) and relate the results with two commonly used
      microbiological variables (bacterial biomass and bacterial diversity as revealed
      by DGGE). No previous studies have used such in situ approaches in microbial
      ecology. For biomass and most of the investigated trace metals (Ag, Cd, Sn, Cr,
      Ni, Cu, Pb, and Al) no significant correlations were found. The exceptions were
      Fe, Mn, Co, and As which behave like micronutrients. For bacterial diversity, no
      relevant relationships were found. We conclude that in situ methods are more
      adapted tools for microbial ecologists but that ex situ approaches are still
      necessary.

PMID- 22153909
TI  - Virucidal efficacy of hydrogen peroxide vapour disinfection.
AB  - BACKGROUND: Viral contamination of surfaces is thought to be important in
      transmission. Chemical disinfection can be an effective means of intervention,
      but little is known about the virucidal efficacy of hydrogen peroxide vapour
      (HPV) against enteric and respiratory viruses. AIM: To measure the virucidal
      efficacy of HPV against respiratory and enteric viruses on materials representing
      those found in institutions and homes. METHODS: Poliovirus, human norovirus
      genogroup II.4 (GII.4), murine norovirus 1, rotavirus, adenovirus and influenza A
      (H1N1) virus dried on to stainless steel, framing panel and gauze carriers were
      exposed to HPV 127 ppm for 1h at room temperature in an isolator. Poliovirus was
      also exposed to HPV at different locations in a room. The virucidal effect was
      measured by comparing recoverable viral titres against unexposed controls.
      Polymerase chain reaction was used to evaluate the effect of HPV on viral genome
      reduction. FINDINGS: HPV disinfection resulted in complete inactivation of all
      viruses tested, characterized by >4 log(10) reduction in infectious particles for
      poliovirus, rotavirus, adenovirus and murine norovirus on stainless steel and
      framing panel carriers, and >2 log(10) reduction for influenza A virus on
      stainless steel and framing panel carriers, and for all viruses on gauze
      carriers. Complete inactivation of poliovirus was demonstrated at several
      locations in the room. Reductions in viral genomes were minimal on framing panel
      and gauze carriers but significant on stainless steel carriers; human norovirus
      GII.4 genome was most resistant to HPV treatment. CONCLUSION: HPV could be an
      effective virucidal against enteric and respiratory viruses contaminating in
      house environments.

PMID- 22153910
TI  - The spatial-numerical congruity effect in preschoolers.
AB  - Number-to-space mapping and its directionality are compelling topics in the study
      of numerical cognition. Usually, literacy and math education are thought to shape
      a left-to-right number line. We challenged this claim by analyzing performance of
      preliterate precounting preschoolers in a spatial-numerical task. In our
      experiment, children exhibited a spatial-numerical congruity (SNC) effect during
      a nonsymbolic numerosity comparison (quicker reaction times to smaller sets
      presented on the left side of the screen and to larger ones presented on the
      right side). These findings suggest that left-to-right number ordering may also
      have some sources that are independent of reading and math education. We argue
      that the current explanations of the spatial-numerical link need to be
      reconsidered.

PMID- 22153911
TI  - characters and clues: factors affecting children's extension of knowledge through
      integration of separate episodes.
AB  - Children build up knowledge about the world and also remember individual
      episodes. How individual episodes during which children learn new things become
      integrated with one another to form general knowledge is only beginning to be
      explored. Integration between separate episodes is called on in educational
      contexts and in everyday life as a major means of extending knowledge and
      organizing information. Bauer and San Souci (2010) provided an initial
      demonstration that 6-year-olds extend their knowledge by integrating between
      separate but related episodes; the episodes shared a high level of surface
      similarity. Experiments 1A and 1B of the current research were tests of
      integration under low and high levels of surface similarity, respectively. In
      Experiment 1A, when surface similarity of the episodes was low, 6-year-olds
      integrated between passages of text, yet their performance was not as robust as
      observed previously. In Experiment 1B, when surface similarity of the episodes
      was high, a replication of Bauer and San Souci's results was observed. In
      Experiment 2, we tested whether a "hint" to consult the information learned in
      the passages improved performance even when surface level similarity was low. The
      hint had a strong facilitating effect. Possible mechanisms of integration between
      separate yet related episodes are discussed.

PMID- 22153912
TI  - The early determination of circulating TRAIL levels does not predict the
      development of pre-eclampsia.

PMID- 22153913
TI  - Impact of genetic background on placental glycogen storage in mice.
AB  - 129 and C57BL/6 are two of the most widely used laboratory mouse strains. While
      it is well known that genetic modifiers between the two strains can directly
      influence embryonic and adult phenotypes, less is known regarding morphological
      differences in placental development. Here we identify differences in the
      junctional zone, glycogen storage and the maternal-fetal interface between these
      two strains and provide examples where these differences impact the phenotypic
      characterisation of placental mutations.

PMID- 22153914
TI  - Value and prognostic significance of mitotic rate in a retrospective series of
      pT1 cutaneous malignant melanoma patients.
AB  - INTRODUCTION: Patients affected by thin melanomas (<=1mm) generally have a good
      prognosis; however, some have a recurrence and eventually die of the disease. The
      seventh edition of the American Joint Committee on Cancer (AJCC) melanoma staging
      system, introduced mitotic rate (MR) as one of the primary criteria for staging
      thin melanoma. MATERIALS AND METHODS: In this study, we sought to determine the
      prognostic value of mitotic rate in a retrospective cohort of localized primary
      cutaneous melanoma patients. RESULTS: In total, 286 cases of pT1 primary
      malignant melanoma occurring in the period 2003-2008 were evaluated. Mitotic
      counts were re-assessed on standard sections of cases without mitosis and with at
      least 1 mitosis at diagnosis; 5-year follow-up and recurrence-free survival were
      available for all patients. Of the 56 radically treated pT1b melanoma patients, 4
      (7.1%) had recurrent disease. These data support the efficacy of the
      incorporation of mitogenicity into AJCC staging for localized cutaneous melanoma
      and indicate the difficulties in the accuracy and reproducibility of the mitotic
      count system.

PMID- 22153915
TI  - Similarity of SABRE field dependence in chemically different substrates.
AB  - The Non-Hydrogenative Parahydrogen-Induced Polarization (NH-PHIP) technique,
      which is referred to as Signal Amplification by Reversible Exchange (SABRE), has
      been reported to be applicable to various substrates and catalysts. For more
      detailed studies, pyridine was mainly examined in the past. Here, we examined
      several pyrazole derivatives towards their amenability to this method using
      Crabtree's Catalyst, which is the polarization transfer catalyst that is best
      documented. Additionally, the dependence of the signal enhancement on the field
      strength, at which the polarization step takes place, was examined for pyridine
      and four different pyrazoles. To achieve this, the polarization step was
      performed at numerous previously determined magnetic fields in the stray field of
      the NMR spectrometer. The substrate dependence of the field dependence proved to
      be relatively small for the different pyrazoles and a strong correlation to the
      field dependence for pyridine was observed. Reducing the number of spins in the
      catalyst by deuteration leads to increased enhancement. This indicates that more
      work has to be invested in order to be able to reproduce the SABRE field
      dependence by simulations.

PMID- 22153916
TI  - In patients with schizophrenia, symptoms improvement can be uncorrelated with
      quality of life improvement.
AB  - OBJECTIVES: Quality of life has been found to be associated with symptoms in
      patients with schizophrenia. Nevertheless, the mechanism that underlies this
      association is still unclear. The objective of this paper is to prospectively
      evaluate the quality of life of patients with schizophrenia in relation to the
      concurrent evolution of their symptoms, their expectations and their perceived
      position in life. METHODS: Participants included 306 outpatients with
      schizophrenia who were interviewed at baseline, 6 and 12 months, about their
      quality of life (Outcome revealed by Preference in Schizophrenia, OPS) and
      symptoms (Positive and Negative Syndrome Scale, PANSS). RESULTS: Quality of life
      relative to subject expectations remained stable over time. A decrease in
      symptoms was correlated to an increase in both expectations and perceived
      position in life but did not correlate to quality of life. CONCLUSION: The level
      of expectations seems to play a major role in the subjective assessment of
      quality of life in patients with schizophrenia. Symptom improvement is not
      necessarily associated with quality of life improvement relative to subject
      expectations. Caregivers should be aware of this result so as to deal with
      possible disappointments in patients receiving a new efficient treatment.

PMID- 22153917
TI  - Neuroprotective effects of osthole pretreatment against traumatic brain injury in
      rats.
AB  - Osthole, a coumarin compound isolated from the plant-derived herb Cnidium
      monnieri, has been the subject of considerable interest because of its broad
      spectrum of pharmacological properties. The aim of this study was to investigate
      the potential protective effects of osthole in adult rats in the setting of
      traumatic brain injury (TBI). We employed Feeney's weight-drop model to ascertain
      whether intraperitoneal administration of osthole (10mg/kg, 20mg/kg and 40 mg/kg)
      30 min before TBI could reduce the severity of neurological deficits, cerebral
      edema, and hippocampal neuron loss. The levels of malondialdehyde (MDA) and
      glutathione (GSH), the activity of superoxide dismutase (SOD), the expressions of
      Bcl-2, Bax, and active caspase-3, and the number of terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells were
      also measured to characterize the antioxidative and antiapoptotic properties. A
      significant reduction of neurological deficits, cerebral edema and hippocampal
      neuron loss was observed in the osthole pretreatment groups (20mg/kg and 40
      mg/kg, but not 10mg/kg) by 24h after TBI compared with the TBI group.
      Furthermore, pretreatment with osthole (40 mg/kg) significantly increased the
      activity of SOD, the level of GSH, and the ratio of Bcl-2/Bax, and also reduced
      the level of MDA, the expression of active caspase-3, and the number of apoptotic
      cells at 24h after TBI. In summary, these results suggested that osthole had a
      neuroprotective effect against TBI, and the protection may be associated with its
      antioxidative and antiapoptotic functions.

PMID- 22153918
TI  - Isolated trapezium subluxation in EMS provider with a novel reduction technique.
AB  - Hand injuries are a common complaint in the emergency department (ED).
      Oftentimes, these injuries occur in work settings. We report a case of a healthy
      EMS provider presenting to the ED with a left thumb injury that turned out to be
      an isolated trapezium subluxation.Using bedside fluoroscopy, the thumb
      carpometacarpal joint was isolated, injected, and subsequently reduced. The
      clinical course and management are discussed as well as a brief review of hand
      injuries.

PMID- 22153920
TI  - Suicide and history of childhood trauma among street youth.
AB  - BACKGROUND: Street youth represent a marginalized population marked by early
      mortality and elevated risk for suicide. It is not known to what extent childhood
      abuse and neglect predispose to suicide in this difficult-to-study population.
      This study is among the first to examine the relationship between childhood
      trauma and subsequent attempted suicide during adolescence and young adulthood
      among street youth. METHODS: From October 2005 to November 2007, data were
      collected for the At Risk Youth Study (ARYS), a cohort of 495 street-recruited
      youth aged 14-26 in Vancouver, Canada. Self-reported attempted suicide in the
      preceding six months was examined in relation to childhood abuse and neglect, as
      measured by the Childhood Trauma Questionnaire (CTQ), using logistic regression.
      RESULTS: Overall, 46 (9.3%) youth reported a suicide attempt during the preceding
      six months. Childhood physical and sexual abuse were highly prevalent, with 201
      (40.6%) and 131 (26.5%) of youth reporting history of each, respectively.
      Increasing CTQ score was related to risk for suicide attempt despite adjustment
      for confounders (adjusted odds ratio [AOR], 1.45 per standard deviation increase
      in score; 95% confidence interval [CI], 1.08-1.91). LIMITATIONS: Use of snowball
      sampling may not have produced a truly random sample, and reliance on self-report
      may have resulted in underreporting of risk behaviors among participants.
      Moreover, use of cross-sectional data limits the degree to which temporality can
      be concluded from the results of this study alone. CONCLUSIONS: There exists a
      strong and graded association between childhood trauma and subsequent attempted
      suicide among street youth, an otherwise 'hidden' population. There is a need for
      effective interventions that not only prevent maltreatment of children but also
      aid youth at increased risk for suicide given prior history of trauma.

PMID- 22153921
TI  - Temperature change dominates the suicidal seasonality in Taiwan: a time-series
      analysis.
AB  - OBJECTIVE: The arguments between bioclimatic and sociodemographic hypotheses for
      the suicidal seasonality continue. The present study aimed to examine the
      relationships between suicidal seasonality and the climate as well as the
      economic factors. METHODS: The monthly suicide death rates of the total, male and
      female populations in Taiwan during January 1991-December 2010 were obtained from
      the population-based database. Autoregressive integrated moving average
      (ARIMA)/seasonal ARIMA (SARIMA) was used to analyze suicidal seasonality, with
      monthly ambient temperature, temperature increase, rainfall, sunlight,
      unemployment and labor force participation rates as the independent inputs.
      RESULTS: The models revealed that monthly temperature increase was strongly
      positively associated with seasonality of suicide rates of all populations
      (beta=0.0184, P<0.001; beta=0.0234, P=0.001; beta=0.0145, P<0.001, respectively).
      Rainfall was significantly negatively associated with the total and male suicide
      rates (beta=-0.0001, P=0.012; beta=-0.0002, P=0.043, respectively), but not with
      female. Unemployment and labor force participation rates were not significantly
      related to their corresponding suicide rates. LIMITATIONS: Socio-demographic
      data, individual major events, and subgroups by suicide methods were not taken
      into account. CONCLUSIONS: The results indicate that, as far as suicidal
      seasonality is concerned, monthly temperature increase is the most influential
      factor, and climatic factors have more significant effect than the economic
      factors.

PMID- 22153922
TI  - The association between sunshine duration and paroxetine response time in
      patients with major depressive disorder.
AB  - INTRODUCTION: A recent study indicates that the serotonin transporter function
      varies with the duration of monthly sunshine. This finding may suggest that the
      efficacy of serotonin selective reuptake inhibitors (SSRIs) is associated with
      the duration of monthly sunshine, but information on this possible association is
      lacking. METHODS: Ninety-one Japanese subjects with depression completed a 6-week
      treatment with paroxetine. Clinical evaluation was performed using the Montgomery
      and Asberg Depression Rating Scale (MADRS) before treatment and after 1, 2, 4 and
      6 weeks of treatment. Data on the duration of monthly sunshine were obtained from
      the meteorological agency website. We divided the patients into four groups:
      nonresponders (NRs), later responders (LRs), early responders (ERs) and ultra
      early responders (UERs). RESULTS: The responses to paroxetine treatment of the
      group that began treatment in fall and winter and of the group that began
      treatment in spring and summer did not differ significantly. The effect of the
      duration of monthly sunshine on paroxetine response time did not differ
      significantly among the four groups, whereas the change in the duration of
      monthly sunshine had a significant effect on paroxetine response time.
      LIMITATIONS: Our sample of patients with MDD was small and only included the
      Hirosaki area. CONCLUSION: The change in the duration of monthly sunshine is
      associated with paroxetine response time.

PMID- 22153923
TI  - Intelligent quotient estimation of mental retarded people from different
      psychometric instruments using artificial neural networks.
AB  - OBJECTIVE: The estimation of a person's intelligence quotient (IQ) by means of
      psychometric tests is indispensable in the application of psychological
      assessment to several fields. When complex tests as the Wechsler scales, which
      are the most commonly used and universally recognized parameter for the diagnosis
      of degrees of retardation, are not applicable, it is necessary to use other
      psycho-diagnostic tools more suited for the subject's specific condition. But to
      ensure a homogeneous diagnosis it is necessary to reach a common metric, thus,
      the aim of our work is to build models able to estimate accurately and reliably
      the Wechsler IQ, starting from different psycho-diagnostic tools. METHODS AND
      MATERIALS: Four different psychometric tests (Leiter international performance
      scale; coloured progressive matrices test; the mental development scale; psycho
      educational profile), along with the Wechsler scale, were administered to a group
      of 40 mentally retarded subjects, with various pathologies, and control persons.
      The obtained database is used to evaluate Wechsler IQ estimation models starting
      from the scores obtained in the other tests. Five modelling methods, two
      statistical and three from machine learning, that belong to the family of
      artificial neural networks (ANNs) are employed to build the estimator. RESULTS:
      Several error metrics for estimated IQ and for retardation level classification
      are defined to compare the performance of the various models with univariate and
      multivariate analyses. Eight empirical studies show that, after ten-fold cross
      validation, best average estimation error is of 3.37 IQ points and mental
      retardation level classification error of 7.5%. Furthermore our experiments prove
      the superior performance of ANN methods over statistical regression ones, because
      in all cases considered ANN models show the lowest estimation error (from 0.12 to
      0.9 IQ points) and the lowest classification error (from 2.5% to 10%).
      CONCLUSIONS: Since the estimation performance is better than the confidence
      interval of Wechsler scales (five IQ points), we consider models built very
      accurate and reliable and they can be used into help clinical diagnosis.
      Therefore a computer software based on the results of our work is currently used
      in a clinical center and empirical trails confirm its validity. Furthermore
      positive results in our multivariate studies suggest new approaches for
      clinicians.

PMID- 22153924
TI  - It is time to move on.

PMID- 22153925
TI  - Identifying the best candidate for radical prostatectomy among patients with high
      risk prostate cancer.
AB  - BACKGROUND: The current role of radical prostatectomy (RP) in patients with high
      risk disease remains controversial. OBJECTIVE: To identify which high-risk
      prostate cancer (PCa) patients might have favorable pathologic outcomes when
      surgically treated. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 1366 patients
      with high-risk PCa (ie, at least one of the following risk factors: prostate
      specific antigen [PSA]>20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and
      pelvic lymph node dissection (PLND) at eight European centers between 1987 and
      2009. A favorable pathologic outcome was defined as specimen-confined (SC)
      disease-namely, pT2-pT3a, node negative PCa with negative surgical margins.
      INTERVENTION: All patients underwent radical retropubic prostatectomy and PLND.
      MEASUREMENTS: Univariable and multivariable logistic regression models tested the
      association between predictors and SC disease. A logistic regression coefficient
      based nomogram was developed and internally validated using 200 bootstrap
      resamples. The Kaplan-Meier method was used to depict biochemical recurrence
      (BCR) and cancer-specific survival (CSS) rates. RESULTS AND LIMITATIONS: Overall,
      505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie,
      age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent
      predictors of SC PCa at RP (all p<=0.04). Patients with SC disease had
      significantly higher 10-yr BCR-free survival and CSS rates than patients without
      SC disease at RP (66% vs 47% and 98 vs 88%, respectively; all p<0.001). A
      nomogram including PSA, age, clinical stage, and biopsy Gleason sum demonstrated
      72% accuracy in predicting SC PCa. This study is limited by its retrospective
      design and by the lack of an external validation of the nomogram. CONCLUSIONS:
      Roughly 40% of patients with high-risk PCa have SC disease at final pathology.
      These patients showed excellent long-term outcomes when surgically treated, thus
      representing the ideal candidates for RP as the primary treatment for PCa.
      Prediction of such patients is possible using a nomogram based on routinely
      available clinical parameters.

PMID- 22153926
TI  - Systematic review of methods for reporting combined outcomes after radical
      prostatectomy and proposal of a novel system: the survival, continence, and
      potency (SCP) classification.
AB  - CONTEXT: Although oncologic results remain the main outcome assessment for
      radical prostatectomy (RP), there is a need to include both urinary continence
      and potency recovery in the assessment of success for this procedure.
      Unfortunately, the widely used trifecta system does not weigh these outcomes
      differently. Moreover, the trifecta system-and even more so, the recently
      described pentafecta system-is only applicable in preoperatively continent and
      potent patients who receive bilateral nerve-sparing RP, and thus it is not an
      appropriate reporting tool for the majority of patients undergoing RP. OBJECTIVE:
      Perform a systematic review to evaluate critically the trifecta and pentafecta
      models and describe a novel system that can be used to report the most relevant
      intermediate- and long-term outcomes after RP. This system has increased
      generalizability by being applicable to all patients undergoing RP. EVIDENCE
      ACQUISITION: A literature search was performed in March 2011 using the Medline,
      Embase, and Web of Science databases. The Medline search included only a free
      text protocol using the terms radical prostatectomy, trifecta, and pentafecta
      across the Title and Abstract fields of the records. Subsequently, the following
      limits were used: humans, gender (male), and language (English). The searches of
      the Embase and Web of Science databases used the same free-text protocol and the
      same keywords, applying no limits. EVIDENCE SYNTHESIS: Eleven original articles
      reported trifecta outcomes, and only one original article used the pentafecta
      model. These systems were correctly applied in only 28-62% of treated patients. A
      mean of 57% (range: 20-83%) of patients achieved continence and potency without
      prostate-specific antigen failure after RP. All the original articles were
      surgical series (level 4 evidence). The new proposed system categorizes the three
      outcomes using the letter S for biochemical disease-free survival, the letter C
      for urinary continence, and the letter P for potency recovery. This SCP system
      can be applied to all patients who undergo RP and is thus analogous to the use of
      the TNM system for classifying disease stage. Moreover, the SCP system allows us
      to distinguish four different clinical scenarios: (1) oncologic and functional
      success, (2) oncologic success and functional failure, (3) oncologic failure and
      functional success, and (4) oncologic and functional failure. CONCLUSIONS: The
      proposed novel SCP system offers the opportunity to appropriately classify all
      patients who undergo RP according to the oncologic and functional outcomes of
      relevance to them on an individual basis. We contend that this system's greater
      generalizability may make it more useful than the currently used trifecta and
      pentafecta systems, though its validation remains to be performed.

PMID- 22153927
TI  - 180-W XPS GreenLight laser therapy for benign prostate hyperplasia: early safety,
      efficacy, and perioperative outcome after 201 procedures.
AB  - BACKGROUND: Photoselective vaporisation of the prostate has evolved from the
      GreenLight 80-W KTP powered laser to the latest 180-W XPS laser involving a MoXy
      fibre. OBJECTIVE: Evaluate the prevalence of perioperative complications and
      short-term outcome for the first time with the XPS laser in men with lower
      urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE). DESIGN,
      SETTING, AND PARTICIPANTS: Prospective data were collected from consecutive
      patients at seven centres worldwide during June 2010 and March 2011. Indication
      for surgery was based on the European Association of Urology and the American
      Urological Association guidelines. Patients receiving anticoagulants or those
      with retention were included and analysed separately. INTERVENTION: 180-W XPS
      GreenLight laser prostatectomy using the MoXy fibre. MEASUREMENTS: Standard
      parameters associated with transurethral prostate surgery and perioperative
      prevalence of surgery-associated problems or complications were documented.
      RESULTS AND LIMITATIONS: A total of 201 patients were included in the study. Mean
      follow-up was 5.8 mo (standard deviation [SD]: 2.8; range: 1-12 mo). A quarter of
      the patients had a prostate volume>=80 ml. For prostates between 51 and 60 ml, a
      mean of 300 kJ (SD: 112) of energy was applied (lasing time: 35.0 min; SD: 15).
      Statistically significant improvements were noted in all key parameters
      postoperatively. The prevalence of perioperative complications was low.
      Limitations of the study are short duration of follow-up and limited number of
      available patients for the functional follow-up. CONCLUSIONS: The 180-W
      GreenLight XPS laser is a new effective treatment option with a low prevalence of
      perioperative complications for patients suffering from LUTS due to BPE.

PMID- 22153928
TI  - Use of Carr-Purcell pulse sequence with low refocusing flip angle to measure T1
      and T2 in a single experiment.
AB  - The Carr-Purcell pulse sequence, with low refocusing flip angle, produces echoes
      midway between refocusing pulses that decay to a minimum value dependent on T(2).
      When the refocusing flip angle was pi/2 (CP(90)) and tau>T(2), the signal after
      the minimum value, increased to reach a steady-state free precession regime
      (SSFP), composed of a free induction decay signal after each pulse and an echo,
      before the next pulse. When tau<T(2), the signal increased from the minimum value
      to the steady-state regime with a time constant (T)=2T(1)T(2)/(T(1)+T(2))(,)
      identical to the time constant observed in the SSFP sequence, known as the
      continuous wave free precession (CWFP). The steady-state amplitude obtained with
      M(CP90)=M(0)T(2)/(T(1)+T(2)) was identical to CWFP. Therefore, this sequence was
      named CP-CWFP because it is a Carr-Purcell sequence that produces results similar
      to the CWFP. However, CP-CWFP is a better sequence for measuring the longitudinal
      and transverse relaxation times in single scan, when the sample exhibits
      T(1)~T(2). Therefore, this sequence can be a useful method in time domain NMR and
      can be widely used in the agriculture, food and petrochemical industries because
      those samples tend to have similar relaxation times in low magnetic fields.

PMID- 22153929
TI  - An expansion of the field modulus suitable for the description of strong field
      gradients in axisymmetric magnetic fields: application to single-sided magnet
      design, field mapping and STRAFI.
AB  - Mapping (or plotting) the magnetic field has a critical importance for the
      achievement of the homogeneous magnetic field necessary to standard MR
      experiments. A powerful tool for this purpose is the Spherical Harmonic Expansion
      (SHE), which provides a simple way to describe the spatial variations of a field
      in free space. Well-controlled non-zero spatial variations of the field are
      critical to MRI. The resolution of the image is directly related to the strength
      of the gradient used to encode space. As a result, it is desirable to have strong
      variations of the field. In that case, the SHE cannot be used as is, because the
      field modulus variations are affected by the variations of all components of the
      field. In this paper, we propose a method based on the SHE to characterize such
      variations, theoretically and experimentally, in the limit of an axisymmetric
      magnetic field. Practical applications of this method are proposed through the
      examples of single-sided magnet design and characterization, along with Stray
      Field Imaging (STRAFI).

PMID- 22153930
TI  - Interdependence of stromal and immune cells for lymph node function.
AB  - Lymph nodes are strategically located throughout the body to allow lymphocytes to
      efficiently encounter their cognate antigen and become activated. The structure
      of the lymph nodes is such that B and T lymphocytes each have their own
      microdomain. This structure is provided by lymph node stromal cells, which also
      provide the lymphocytes with a scaffold upon which to migrate. Here, we discuss
      how stromal cells differentiate from mesenchymal precursor cells in response to
      the interaction with lymphocytes, while these stromal cells in turn provide
      necessary survival factors for the lymphocytes. We propose that during immune
      reactions, the interactions of stromal and immune cells are similarly important
      for controlling the expanding lymphocyte pool.

PMID- 22153931
TI  - Boosting antibody responses by targeting antigens to dendritic cells.
AB  - Delivering antigens directly to dendritic cells (DCs) in situ, by injecting
      antigens coupled to antibodies specific for DC surface molecules, is a promising
      strategy for enhancing vaccine efficacy. Enhanced cytotoxic T cell responses are
      obtained if an adjuvant is co-administered to activate the DC. Such DC targeting
      is also effective at enhancing humoral immunity, via the generation of T
      follicular helper cells. Depending on the DC surface molecule targeted, antibody
      production can be enhanced even in the absence of adjuvants. In the case of
      Clec9A as the DC surface target, enhanced antibody production is a consequence of
      the DC-restricted expression of the target molecule. Few other cells absorb the
      antigen-antibody construct, therefore, it persists in the bloodstream, allowing
      sustained antigen presentation, even by non-activated DCs.

PMID- 22153933
TI  - [About marginal age lung donors].

PMID- 22153932
TI  - [Variability in renal dysfunction defining criteria and detection methods in
      intensive care units: are the international consensus criteria used for
      diagnosing renal dysfunction?].
AB  - OBJECTIVE: To evaluate variability in the detection and prevention of acute
      kidney injury (AKI) in the intensive care unit (ICU), and application of the
      international recommendations in this field (Acute Dialysis Quality Initiative
      [ADQI] and Acute Kidney Injury Network [AKIN]). DESIGN: A prospective,
      observational, multicenter study. SETTING: A total of 42 ICUs in 32 hospitals
      (78% in third level hospitals and 70.7% general units) recruited for a study on
      the prevalence of AKI (COFRADE). INTERVENTIONS: Survey. VARIABLES: Aspects
      related to AKI detection and prevention and renal replacement therapy protocols.
      RESULTS: The method used for estimating glomerular filtration rate was serum
      creatinine in 36.6%, creatinine clearance in 41.5% and equations in 22%; none
      reported using cystatin-C. Only 39.1% ICUs acknowledged the use of stratification
      systems (13 RIFLE and 3 AKIN). A total of 48.8% ICUs had no written protocols for
      AKI prevention, 31.7% reported using them only for contrast nephropathy, 7.3% for
      nephrotoxic drugs and 12.2% for both. In contrast, 63.4% participants had written
      protocols for renal replacement therapy, 70.7% had implemented a training
      program, and 53.7% had some method for adjusting doses of drugs when on renal
      replacement therapy. CONCLUSIONS: We observed important variability regarding
      diagnostic criteria and prevention of AKI in Spanish ICUs, the application of
      ADQI or AKIN recommendations still being low in our units. Renal replacement
      therapy seems to generate more concern among our intensivists than AKI
      management.

PMID- 22153935
TI  - Structural requirements for hybridization at the 5'-position are different in
      alpha-l-LNA as compared to beta-D-LNA.
AB  - The synthesis and biophysical evaluation of R and S-5'-Me-alpha-l-LNA nucleoside
      phosphoramidites and modified oligo-2'-deoxyribonucleotides is reported.
      Synthesis of the nucleoside phosphoramidites was accomplished in multi-gram
      quantities starting from diacetone glucose. The 5'-methyl group in the S
      configuration was introduced by reacting the sugar 5'-aldehyde with MeMgBr.
      Synthesis of the R-5'-Me isomer was accomplished from the S-5'-Me nucleoside by a
      late stage inversion using Mitsunobu conditions. Evaluation of the modified
      oligonucleotides in thermal denaturation experiments revealed that R-5'-Me-alpha
      l-LNA showed similar RNA affinity as alpha-l-LNA while the S-5'-Me analog was
      less stabilizing. This result is in contrast to the beta-d-series where the S-5'
      Me isomer showed LNA-like affinity for RNA while the R-5'-Me group completely
      reversed the stabilization effect on duplex thermostability.

PMID- 22153934
TI  - Efficient photodynamic therapy of cancer using chemotherapeutic porphyrin
      ruthenium metalla-cubes.
AB  - Two cationic octanuclear metalla-cubes [Ru(8)(eta(6)-C(6)H(5)Me)(8)(tpp
      H2)(2)(dhbq)(4)](8+) and [Ru(8)(eta(6)-p-iPrC(6)H(4)Me)(8)(tpp
      H2)(2)(dhbq)(4)](8+) were prepared and evaluated as dual photosensitizers and
      chemotherapeutics in cancer cells. In the dark, the complexes presented high
      cytotoxicity towards only melanoma and ovarian cancer cells. However, the
      complexes exhibited good phototoxicities toward all cancer cells (1MUM
      concentration, LD(50)=2-7J/cm(2)), thus suggesting a dual synergistic effect with
      good properties of both the arene ruthenium chemotherapeutics and the porphyrin
      photosensitizers.

PMID- 22153936
TI  - Structure-activity relationship studies of S1P agonists with a dihydronaphthalene
      scaffold.
AB  - Structure-activity relationship (SAR) of sphingosine-1-phosphate receptor
      agonists with a dihydronaphthalene scaffold was investigated. Compound 1 was
      modified to improve S1P(1) agonistic activity and in vivo peripheral lymphocyte
      lowering (PLL) activity without impairing selectivity over S1P(3) agonistic
      activity. A detailed SAR study of the terminal lipophilic part revealed that the
      introduction of substituents on the propylene linker and the terminal benzene
      ring influences in vitro and PLL activities. Compound 6n bearing a (S)-methyl
      group at the 2-position on the propylene linker and chlorine at the para-position
      on the terminal benzene ring showed potent hS1P(1) agonistic activity with
      excellent selectivity over hS1P(3) and in vivo PLL activity in mice.

PMID- 22153938
TI  - Physicochemical properties and inhibition effect on iron deficiency anemia of a
      novel polysaccharide-iron complex (LPPC).
AB  - Porphyran (P) was extracted from red algae Porphyra by boiling water. A novel
      polysaccharide-iron complex (LPPC) was prepared under the alkaline condition by
      adding a ferric chloride solution to the low molecular weight porphyran (LP)
      solution. Physicochemical properties and inhibition effect on iron deficiency
      anemia of this complex were studied. The content of iron(III) in the complex is
      21.57% determined with iodometry. The results indicate that LPPC was product
      required. The complex can increase red blood cell count (RBC), hemoglobin (Hb),
      Serum iron (SI), spleen index, spleen mass and mass of mice with iron deficiency
      anemia (IDA). Although the structure and deeper mechanisms on hemolytic anemia of
      LPPC should be further studied, LPPC is hoped to be developed as a late-model
      iron supplement which has a synergism on anemia.

PMID- 22153937
TI  - Novel brain penetrant benzofuropiperidine 5-HT6 receptor antagonists.
AB  - 7-Arylsulfonyl substituted benzofuropiperidine was discovered as a novel scaffold
      for 5HT(6) receptor antagonists. Optimization by substitution at C-1 position led
      to identification of selective, orally bioavailable, brain penetrant antagonists
      with reduced hERG liability. An advanced analog tested in rat social recognition
      model showed significant activity suggesting potential utility in the enhancement
      of short-term memory.

PMID- 22153939
TI  - Synthesis and antibacterial activity of a novel series of acylides active against
      community acquired respiratory pathogens.
AB  - A novel series of acylides 4 were designed to overcome antibacterial resistance
      and evaluated for in vitro and in vivo activity. This series of acylides was
      designed from clarithromycin by changing the substitution on the desosamine
      nitrogen, followed by conversion to 3-O-acyl and 11,12-carbamate. These compounds
      showed significantly potent antibacterial activity against not only Gram-positive
      pathogens, including macrolide-lincosamide-streptogramin B (MLS(B))-resistant and
      efflux-resistant strains, but also Gram-negative pathogens such as Haemophilus
      influenzae. These acylides also showed better activity against telithromycin
      resistant Streptococcus pneumoniae strains.

PMID- 22153940
TI  - Synthesis of [11C]uric acid, using [11C]phosgene, as a possible biomarker in PET
      imaging for diagnosis of gout.
AB  - The synthesis and in vivo evaluation of (11)C -labeled uric acid ([(11)C]1), a
      potential imaging agent for the diagnosis of urate-related life-style diseases,
      was performed using positron emission tomography (PET) image analysis. First, the
      synthesis of [(11)C]1 was achieved by reacting 5,6-diaminouracil (2) with (11)C
      labeled phosgene ([(11)C]COCl(2)). The radiochemical yield of [(11)C]1 was 37+/
      7% (decay-corrected based on [(11)C]COCl(2)) with specific radioactivities of 96
      152GBq/MUmol at the end of synthesis (n=6). The average time of radiosynthesis
      from the end of bombardment, including formulation, was about 30min with >98%
      radiochemical purity. Second, the synthetic approach to [(11)C]1 was optimized
      using 5,6-diaminouracil sulfate (3) with [(11)C]COCl(2) in the presence of 1,8
      bis(dimethylamino)naphthalene. [(11)C]1 was synthesized in 36+/-6% radiochemical
      yield, 89-142GBq/MUmol of specific radioactivities, and 98% radiochemical purity
      by this method (n=5). This allowed the synthesis of [(11)C]1 to be carried out
      repeatedly and the radiochemical yield, specific radioactivities, average time of
      synthesis, and radiochemical purity of [(11)C]1 were similar to those obtained
      using 2. PET studies in rats showed large differences in the accumulation of
      radioligand in the limbs under normal and hyperuricemic conditions. Thus, an
      efficient and convenient automated synthesis of [(11)C]1 has been developed, and
      preliminary PET evaluation of [(11)C]1 confirmed the increased accumulation of
      radioactivity in the limbs of a rat model of hyperuricemia.

PMID- 22153941
TI  - Lead optimisation of selective non-zinc binding inhibitors of MMP13. Part 2.
AB  - Directed screening has identified a novel series of non-zinc binding MMP13
      inhibitors that possess good levels of activity whilst demonstrating excellent
      selectivity over related MMPs. A lead optimisation campaign has delivered
      compounds with enhanced MMP13 potency, good selectivity and acceptable
      bioavailability profiles leading to a predicted twice-a-day dosing regimen in
      man.

PMID- 22153942
TI  - 5-HT2c receptor selectivity and structure-activity relationship of N-methyl-N-(1
      methylpiperidin-4-yl)benzenesulfonamide analogs.
AB  - Agonists of the 5-HT(2C) receptor have attracted much attention as therapeutic
      agents for the treatment of obesity. Subtype selectivity against other 5-HT(2)
      receptors is one of the most important prerequisites for reducing side effects.
      We present the synthesis of N-methyl-N-(1-methylpiperidin-4-yl)benzenesulfonamide
      analogs and their structure-activity relationship studies on 5-HT(2A) and 5
      HT(2C) receptors. Although the compounds showed nanomolar activity to the 5
      HT(2C) receptor, their selectivity against the 5-HT(2A) receptor was modest to
      low. Molecular modeling studies using homology modeling and docking simulation
      revealed that selectivity originated from subtype specific residues. The observed
      binding modes and receptor-ligand interactions provided us a clue for optimizing
      the selectivity against the 5-HT(2A) receptor.

PMID- 22153943
TI  - Contingency management in substance abuse treatment: a structured review of the
      evidence for its transportability.
AB  - AIMS: Extant literature on contingency management (CM) transportability, or its
      transition from academia to community practice, is reviewed. The Consolidated
      Framework for Implementation Research (CFIR; Damschroder et al., 2009) guides the
      examination of this material. METHODS: PsychInfo and Medline database searches
      identified 27 publications, with reviewed reference lists garnering 22 others.
      These 49 sources were examined according to CFIR domains of the intervention,
      outer setting, inner setting, clinicians, and implementation processes. RESULTS:
      Intervention characteristics were focal in 59% of the identified literature, with
      less frequent focus on clinicians (34%), inner setting (32%), implementation
      processes (18%), and outer setting (8%). As intervention characteristics,
      adaptability and trialability most facilitate transportability whereas non
      clinical origin, perceived inefficacy or disadvantages, and costs are
      impediments. Clinicians with a managerial focus and greater clinic tenure and CM
      experience are candidates to curry organizational readiness for implementation,
      and combat staff disinterest or philosophical objection. A clinic's technology
      comfort, staff continuity, and leadership advocacy are inner setting
      characteristics that prompt effective implementation. Implementation processes in
      successful demonstration projects include careful fiscal/logistical planning,
      role-specific staff engagement, practical adaptation in execution, and evaluation
      via fidelity-monitoring and cost-effectiveness analyses. Outer setting
      characteristics-like economic policies and inter-agency networking or competition
      are salient, often unrecognized influences. CONCLUSIONS: As most implementation
      constructs are still moving targets, CM transportability is in its infancy and
      warrants further scientific attention. More effective dissemination may
      necessitate that future research weight emphasis on external validity, and
      utilize models of implementation science.

PMID- 22153944
TI  - Diagnostic criteria for cannabis withdrawal syndrome.
AB  - OBJECTIVE: Cannabis withdrawal occurs in frequent users who quit, but there are
      no accepted diagnostic criteria for a cannabis withdrawal syndrome (CWS). This
      study evaluated diagnostic criteria for CWS proposed in DSM-V and two earlier
      proposals. METHOD: A convenience sample of 384 adult, non-treatment-seeking
      lifetime cannabis smokers provided retrospective self-report data on their "most
      difficult" quit attempt without formal treatment, which was used in this
      secondary analysis. Prevalence, time of onset, and peak intensity (5-point Likert
      scale) for 39 withdrawal symptoms (drawn from the literature) were assessed via
      computer-administered questionnaire. Subject groups were compared using chi
      square or ANOVA. Symptom clustering was evaluated with principal components
      analysis. RESULTS: 40.9% of subjects met the DSM-V criterion of >=3 symptoms from
      a list of 7. There were no associations with sex, race, or type of cannabis
      preparation used. There were significant positive associations between duration
      or frequency of cannabis use prior to the quit attempt and experiencing CWS.
      Subjects with CWS had a significantly shorter duration of abstinence. Alternative
      syndromal criteria (dropping physical symptoms from DSM-V list; requiring >=2 or
      >=4 symptoms from a list of 11) yielded a similar prevalence of CWS and similar
      associations with prior cannabis use and relapse. The PCA yielded 12 factors,
      including some symptom clusters not included in DSM-V. CONCLUSIONS: Findings
      support the concurrent and predictive validity of the proposed DSM-V CWS, but
      suggest that the list of withdrawal symptoms and number required for diagnosis
      warrant further evaluation.

PMID- 22153945
TI  - Total knee arthroplasty in a patient with hemophilic arthropathy and high-titer
      inhibitors: a cost analysis.
AB  - A patient with hemophilia A, who developed factor VIII inhibitors and initially
      had funding for his total knee arthroplasty declined, is discussed. A total of L1
      542 000 (US $2 474 603) was spent on medical treatment for recurrent hemarthroses
      over a 4-year period, while funding was sought. In comparison, the total cost for
      his knee arthroplasty was L542 858 (US $871 084) including perioperative
      recombinant clotting factors. Postoperatively, with 1-year follow-up, no further
      hemoarthroses have occurred; his analgesic requirement is significantly reduced;
      he has a much improved level of function; and treatment costs are significantly
      reduced, leading to a substantial overall saving. Our findings suggest that
      surgical treatment is beneficial and cost-effective for patients with hemophilia
      with inhibitors. Hospitals should not deny operative treatment based on cost
      alone.

PMID- 22153946
TI  - The optimal skin incision for minimally invasive total hip arthroplasty performed
      via the anterolateral approach.
AB  - Twelve total hip arthroplasty procedures were performed in fresh cadaveric
      specimens via the anterolateral approach using straight 9-cm incisions placed in
      2 different locations with respect to anatomical landmarks. During each
      procedure, the forces applied to the wound edges by each of the hip instruments
      and the pressures and strains generated along the wound edges were measured.
      Pressures ranging from 40 to 190 kPa were developed between the retractors and
      the wound edges during acetabular reaming and femoral rasping. The resulting
      strain along the wound edges averaged 28% during acetabular reaming and 34%
      during femoral broaching (P < .0001). Maximum strains were recorded at the ends
      of each incision and averaged 58% and 61%, respectively (P < .0001). These
      results were independent of the anatomical placement of the skin incision. In
      total hip arthroplasty, the mechanical trauma associated with the procedure is
      primarily determined by the surgical approach to the hip and the properties of
      the subcutaneous tissues, and not the anatomical location of the skin incision
      itself.

PMID- 22153947
TI  - Function and quality of life in patients with recurvatum deformity after primary
      total knee arthroplasty: a review of our joint registry.
AB  - The aim of this paper is to assess function and quality of life in patients with
      recurvatum at 2 years after primary total knee arthroplasty. This prospective
      study involves 2587 total knee arthroplasty from 2004 to 2008 with 2-year follow
      up. Patients' demographics, diagnosis, implants, range of motion, laxity, and
      knee and SF-36 scores were recorded. Recurvatum deformity of 0 degrees , 1
      degrees  to 5 degrees , 6 degrees  to 10 degrees , and more than 10 degrees  were
      classified as grades 0, 1, 2, and 3, respectively. Grade 1 had similar functional
      scores to grade 0 but significantly better SF1, SF4, SF5, and SF8 when compared
      with grades 2 and 3. Patients with mediolateral translation of more than 5 mm
      were more likely to have grades 2 and 3 recurvatum (P = .01), indicating global
      laxity. Postoperative recurvatum of more than 5 degrees  significantly impacts
      function and quality of life of patients.

PMID- 22153948
TI  - Third-generation ceramic-on-ceramic total hip arthroplasty in patients younger
      than 30 years with osteonecrosis of femoral head.
AB  - The purpose of this study was to evaluate the functional and radiographic results
      of patients younger than 30 years who underwent cementless third-generation
      ceramic-on-ceramic total hip arthroplasty for osteonecrosis of the femoral head.
      Forty-one patients (56 hips) with a minimum follow-up of 6 years were included.
      In all cases, third-generation ceramic-on-ceramic articulation was used. Average
      Harris Hip Scores improved from 52.9 preoperatively to 98.2, and Western Ontario
      and McMaster Universities Osteoarthritis Index score, from 95.2 to 25.2. Thirty
      nine patients returned to their normal occupations. No aseptic loosening or
      osteolysis was observed. Total hip arthroplasty performed using third-generation
      ceramic-on-ceramic bearings for osteonecrosis of femoral head was found to
      provide satisfactory clinical and radiologic results, especially in active, young
      patients.

PMID- 22153949
TI  - Anteversion of the acetabular component aligned with the transverse acetabular
      ligament in total hip arthroplasty.
AB  - In total hip arthroplasty (THA), accurately positioning the cup is crucial for
      achieving an adequate postoperative range of motion and stability. For 47 THA
      cases in which the inferomedial rim of the cup had been positioned parallel to
      the transverse acetabular ligament, we retrospectively performed the measurements
      of the radiographic cup anteversion angle relative to the anterior pelvic plane
      using 3-dimensional reconstruction computed tomography. The mean anteversion
      angle was 21.2 degrees , with no significant difference detected in mean cup
      anteversion between the dysplastic hip group (15 hips) and the control group (15
      hips). We suggest that the transverse acetabular ligament is a practical
      anatomical landmark for determining cup anteversion in THA for both dysplastic
      and nondysplastic hip cases.

PMID- 22153951
TI  - Sagittal flexion of the femoral component affects flexion gap and sizing in total
      knee arthroplasty.
AB  - The purpose of this study was to determine how much sagittal rotation of the
      femoral component affects the flexion gap and femoral component sizing using a
      computer-simulation technique. The study comprised 25 knees scheduled for total
      knee arthroplasty (TKA). The femoral component was positioned at -2 degrees , 0
      degrees , 2 degrees , 4 degrees , or 6 degrees  of flexion to the anterior
      femoral cortex, and the resected portion of the posterior medial femoral condyle
      was measured for 3 total knee systems. The amount of the resected bone of the
      posterior medial condyle decreased approximately 1 mm for every 2 degrees  of
      additional flexion in all TKA systems. Intentional sagittal flexion of the
      femoral component by several degrees during TKA can be a useful downsizing
      technique for the femoral component without excessively increasing the flexion
      gap.

PMID- 22153950
TI  - Proximal femoral allograft in revision hip surgery with severe femoral bone loss:
      a systematic review and meta-analysis.
AB  - This study provides an objective appraisal of available evidence regarding the
      outcome of proximal femoral allograft for reconstruction of massive proximal
      femoral bone loss. The primary outcomes were rates of success, structural
      failure, and infection. A systematic literature review identified 16 studies with
      a minimum 2-year follow-up. Estimated pooled effect analysis performed with
      heterogeneity quantified using I(2) and tau(2). The total cohort included 498
      patients with a mean follow-up of 8.1 years. The pooled success rate was 81%,
      pooled structural failure rate of 15%, and pooled infection rate of 8%.
      Significant heterogeneity was observed in structural failure rates (I(2) = 47.9,
      tau(2) = 0.29, P < .05). Proximal femoral allografts afford viable reconstruction
      for massive femoral bone loss when performed by experienced.

PMID- 22153952
TI  - Reduction of surface contamination and biofilms of Enterococcus sp. and
      Staphylococcus aureus using a citrus-based vapour.
AB  - BACKGROUND: Antibiotic-resistant organisms such as meticillin-resistant
      Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus sp. (VRE) are
      an ongoing problem in hospitals. Essential oil vapours (EOs) have been shown to
      reduce environmental bacterial contamination. AIMS: To assess the efficacy of
      Citri-VTM, a vaporized blend of citrus EOs (orange: bergamot, 1:1 v/v) (Belmay,
      Northampton, UK), at removing Enterococcus sp. and S. aureus from stainless steel
      surfaces; and to investigate its effect on the formation of bacterial biofilms.
      METHODS: A microplate assay was used to assess the effect of the citrus vapour on
      the formation of biofilms and their metabolic activity. Biofilm removal from
      stainless steel surfaces was measured by a colorimetric assay and by digital
      microscopy. FINDINGS: The citrus vapour reduced VRE and MRSA on stainless steel
      surfaces by 1.5-3log(10) after 24h exposure. Staphylococcal biofilms were reduced
      both during and after formation, whereas enterococcal biofilms were significantly
      reduced (P<=0.05) only after formation. Metabolic activity decreased by up to 72%
      in strains tested. Two-dimensional digital microscopy showed reductions in
      biofilm coverage of the stainless steel disc by as much as 99.5%. CONCLUSION:
      Citrus vapour has potential for application in the clinical environment, for
      instance as a secondary disinfectant to reduce surface contamination by VRE and
      MRSA.

PMID- 22153953
TI  - Nosocomial postneurosurgical Acinetobacter baumannii meningitis: a retrospective
      study of six cases admitted to Hamad General Hospital, Qatar.
AB  - This article reports six cases of nosocomial Acinetobacter baumannii meningitis
      in patients who had undergone neurosurgical procedures with placing of external
      ventricular drains. The mean time between surgery and onset of infection was 27
      days [standard deviation (SD) 14] Multi-drug resistance was observed in three
      cases (50%) and carbapenem resistance was noted in two cases (33%). All patients
      had received empirical antibiotics and these were appropriate in five cases
      (83%). The mean duration of antimicrobial treatment was 12.5 (SD 2.4) days. Two
      of the six patients (33%) died in hospital.

PMID- 22153954
TI  - Nutritional risk as predictor for healthcare-associated infection among
      hospitalized elderly patients in the acute care setting.
AB  - BACKGROUND: Poor nutritional status is associated with high rates of healthcare
      associated infections (HCAIs) among hospitalized elderly patients. Early
      recognition of patients at risk for HCAIs is important. The Geriatric Nutritional
      Risk Index (GNRI) is a screening tool able to predict nutrition-related
      complications. AIM: To examine the use of GNRI as a predictor of HCAIs in the
      acute care setting. METHODS: A total of 248 consecutive patients aged >65 years,
      admitted as emergencies to the medical ward of an acute care hospital, were
      enrolled. On admission, clinical and laboratory assessment, anthropometric
      measurements, performance status, and GNRI score estimation were performed. HCAIs
      were recorded during admission. FINDINGS: On admission, 53.8% of the patients
      were not at risk, 37.2% at low or medium risk and 8.9% at high risk for nutrition
      related complications, as stratified by using the GNRI. During hospitalization
      23.7% of the patients developed HCAIs. Patients with HCAIs had higher mortality
      (P < 0.001) and longer hospital stay (P < 0.001). In multivariate analysis, a
      performance status >1 [hazard ratio (HR): 2.08; 95% confidence interval (CI):
      1.07-4.02; P = 0.03] and diabetes (HR: 2.57; 95% CI: 1.37-4.84; P = 0.003) were
      associated with increased risk for HCAIs, whereas GNRI score (per unit increase)
      had a protective effect (HR: 0.97; 95% CI: 0.95-0.99; P = 0.01). Well-nourished
      patients (GNRI >98) were significantly more likely to remain free from HCAIs
      during hospitalization (P = 0.003). CONCLUSION: GNRI can accurately stratify
      hospitalized elderly patients according to risk for developing HCAIs.

PMID- 22153956
TI  - PWM-switching pattern-based diagnosis scheme for single and multiple open-switch
      damages in VSI-fed induction motor drives.
AB  - This paper deals with a fault detection technique for insulated-gate bipolar
      transistors (IGBTs) open-circuit faults in voltage source inverter (VSI)-fed
      induction motor drives. The novelty of this idea consists in analyzing the pulse
      width modulation (PWM) switching signals and the line-to-line voltage levels
      during the switching times, under both healthy and faulty operating conditions.
      The proposed method requires line-to-line voltage measurement, which provides
      information about switching states and is not affected by the load. The fault
      diagnosis scheme is achieved using simple hardware and can be included in the
      existing inverter system without any difficulty. In addition, it allows not only
      accurate single and multiple faults diagnosis but also minimization of the fault
      detection time to a maximum of one switching period (T(c)). Simulated and
      experimental results on a 3-kW squirrel-cage induction motor drive are displayed
      to validate the feasibility and the effectiveness of the proposed strategy.

PMID- 22153957
TI  - An electrokinetic/Fe0 permeable reactive barrier system for the treatment of
      nitrate-contaminated subsurface soils.
AB  - Effective nitrate removal by Fe(0) permeable reactive barriers (Fe(0) PRB) has
      been recognized as a challenging task because the iron corrosion product foamed
      on Fe(0) hinders effective electron transfer from Fe(0) to surface-bound nitrate.
      The objectives of this study were (i) to demonstrate the effectiveness of an
      electrokinetic/Fe(0) PRB system for remediating nitrate-contaminated low
      permeability soils using a bench-scale system and (ii) to deepen the
      understanding of the behavior and fate of nitrate in the system. Bench-scale
      laboratory experiments were designed to investigate the influence of the Fe(0)
      content in the permeable reactive barrier, the pH in the anode well, and the
      applied voltage on remediation efficiency. The experimental results showed that
      the major reaction product of nitrate reduction by Fe(0) was ammonium and that
      nitrate reduction efficiency was significantly influenced by the variables
      investigated in this study. Nitrate reduction efficiency was enhanced by either
      increasing the Fe(0) content in the Fe(0) reactive barrier or decreasing the
      initial anode pH. However, nitrate reduction efficiency was reduced by increasing
      the applied voltage from 10 V to 40 V due to the insufficient reaction time
      during nitrate migration through the Fe(0) PRB. For all experimental conditions,
      nearly all nitrate nitrogen was recovered in either anode or cathode wells as
      nitrate or ammonium within 100 h, demonstrating the effectiveness of the system
      for remediating nitrate-contaminated subsurface soils.

PMID- 22153958
TI  - Determining the mechanisms for aerobic granulation from mixed seed of floccular
      and crushed granules in activated sludge wastewater treatment.
AB  - Aerobic granulation is a novel and promising technology for wastewater treatment.
      However, long start-up periods required for the development of granules from
      floccular sludge, and the loss of biomass in this period leading to poor nutrient
      removal performance are key challenges. In a recent study the addition of crushed
      granules to a floccular sludge significantly reduced the start-up period, and
      also maintained the nutrient removal performance during granulation. In this
      study, we examined the mechanisms responsible for the fast granulation from a
      mixture of floccular and granular sludges. Fluorescent microbead particles (4 MUm
      diameter) were successfully applied to differentially label the surfaces of
      floccular and crushed granular aggregates. Labelled flocs and crushed granules
      were added to a laboratory scale wastewater treatment reactor, and the granule
      formation process was monitored using confocal laser scanning microscopy over an
      80 day period. Flocs were observed to attach to the surface of the seeding
      granules, resulting in reduced biomass washout during granulation. This mechanism
      not only reduces the granulation period, but also maintains the nutrient removal
      performance of the reactor. The results indicate that the granules acted as
      nuclei for floccular particle attachment, which accelerated granule formation.

PMID- 22153959
TI  - Runoff of pyrethroid insecticides from concrete surfaces following simulated and
      natural rainfalls.
AB  - Intensive residential use of insecticides has resulted in their ubiquitous
      presence as contaminants in urban surface streams. For pest eradication, urban
      hard surfaces such as concrete are often directly treated with pesticides, and
      wind/water can also carry pesticides onto hard surfaces from surrounding areas.
      This study expanded on previous bench-scale studies by considering pesticide
      runoff caused by irrigation under dry weather conditions and rain during the wet
      season, and evaluated the effects of pesticide residence time on concrete, single
      versus recurring precipitations, precipitation intensity, and concrete surface
      conditions, on pesticide transferability to runoff water. Runoff from concrete 1
      d after pesticide treatment contained high levels of bifenthrin (82 MUg/L) and
      permethrin (5143 MUg/L for cis and 5518 MUg/L for trans), indicating the
      importance of preventing water contact on concrete after pesticide treatments.
      Although the runoff transferability quickly decreased as the pesticide residence
      time on concrete increased, detectable residues were still found in runoff water
      after 3 months (89 d) exposure to hot and dry summer conditions. ANOVA analysis
      showed that precipitation intensities and concrete surface conditions (i.e., acid
      wash, silicone seal, stamping, and addition of microsilica) did not significantly
      affect the pesticide transferability to runoff. For concrete slabs subjected to
      natural rainfalls during the winter wet season, pesticide levels in the runoff
      decreased as the time interval between pesticide application and the rain event
      increased. However, bifenthrin and permethrin were still detected at 0.15-0.17
      and 0.75-1.15 MUg/L in the rain runoff after 7 months (221 d) from the initial
      treatment. In addition, pesticide concentrations showed no decrease between the
      two rainfall events, suggesting that concrete surfaces contaminated by pesticides
      may act as a reservoir for pesticide residues, leading to sustained urban runoff
      contamination.

PMID- 22153960
TI  - Synergetic effect between photocatalytic degradation and adsorption processes on
      the removal of phenolic compounds from olive mill wastewater.
AB  - The photocatalytic degradation of two phenolic compounds, p-coumaric acid and
      caffeic acid, was performed with a suspended mixture of TiO(2) and powdered
      activated carbon (PAC) (at pH=3.4 and 8). Adsorption, direct photolysis and
      photocatalytic degradation were studied under different pH and UV light sources
      (sunlight vs. 365nm UV lamps). The potential for reusing this catalyst mixture in
      sequential photocatalytic runs was examined as well. Quantum yields for the
      direct photolysis of caffeic acid under solar and artificial 365nm light were
      calculated (for the first time) as 0.005 and 0.011, respectively. A higher
      removal rate of contaminants by either adsorption or photocatalysis was obtained
      at a low pH (pH 4). Furthermore, the addition of PAC increased the removal
      efficiency of the phenolic compounds. Fast removal of the pollutants from the
      solution over three sequential runs was achieved only when both TiO(2) and PAC
      were present. This suggests that at medium phenolic concentrations, the presence
      of PAC as a co-sorbent reduces surface poisoning of the TiO(2) catalyst and hence
      improves photocatalysis degradation of phenolic pollutants. The adsorption
      equilibrium of caffeic acid or p-coumaric acid on TiO(2), PAC and the combined
      mixture of TiO(2) and PAC follows the Langmuir isotherm model. Experiments with
      PAC TiO(2) mixture and olive mill wastewater (anaerobically treated and diluted
      by a factor of 10) showed higher removal of polyphenols than of chemical oxygen
      demand (COD). 87% removal of total polyphenols, compared to 58% of COD, was
      achieved after 24h of exposure to 365nm irradiation (7.6W/m(2)) in the presence
      of a suspended mixture of TiO(2) and PAC, indicating "self-selectivity" of
      polyphenols.

PMID- 22153961
TI  - Exposure levels to brominated compounds in seawater swimming pools treated with
      chlorine.
AB  - Despite evidence of formation of brominated compounds in seawater swimming pools
      treated with chlorine, no data about exposure levels to these compounds have been
      reported. To address this issue, a survey has been carried out in four
      establishments (representing 8 pools) fed with seawater and devoted to relaxing
      and cure treatments (thalassotherapy centres located in Southeast of France).
      Carcinogenic and mutagenic brominated disinfection byproducts (trihalomethanes 
      THM- and halogenated acetic acids -HAA-) were quantified at varying levels,
      statistically related to organic loadings brought by bathers, and not from marine
      organic matter, and also linked to activities carried out in the pools (watergym
      vs swimming). Bromoform and dibromoacetic acid, the most abundant THM and HAA
      detected, were measured at levels up to 18-fold greater than the maximum
      contaminant levels of 60 and 80 MUg/L fixed by US.EPA in drinking waters. The
      correlations between these disinfection byproducts and other environmental
      factors such as nitrogen, pH, temperature, free residual chlorine, UV(254),
      chloride and bromide concentrations, and daily frequentation were examined.
      Because thalassotherapy and seawater swimming pools (hotels, cruise ships,...)
      are increasing in use around the world and because carcinogenic and mutagenic
      brominated byproducts may be produced in chlorinated seawater swimming pools,
      specific care should be taken to assure cleanliness of users (swimmers and
      patients taking the waters) and to increase water circulation through media
      filters to reduce levels of brominated byproducts.

PMID- 22153962
TI  - Salivary duct carcinoma: diagnostic clues, histology and treatment.
AB  - Salivary duct carcinoma is a very rare, highly-malignant epithelial tumour. We
      present a case of a 75-year-old man with a rapidly- growing salivary duct
      carcinoma in the parotid gland, of one month's evolution. Histopathologically,
      salivary duct carcinoma is characterised by its resemblance to ductal carcinoma
      of the breast. It usually develops aggressively with possibilities of early
      distant metastasis and local recurrence. The tumour is managed with total
      parotidectomy, ipsilateral neck dissection and adjunctive radiation. In advanced
      cases, we recommend treatment with anti-Her-2 monoclonal antibodies such as
      trastuzumab.

PMID- 22153963
TI  - [Cochleovestibular dysfunction in patients with diabetes mellitus, hypertension
      and dyslipidemia].
AB  - INTRODUCTION AND OBJECTIVE: Polygenic or multifactorial inheritance of chronic
      disorders (MICD) contribute to irreversible cochleovestibular impairment. Our aim
      was to determine the type and degree of cochleovestibular dysfunction (CVD) in
      patients with MICD. METHODS: Cross-sectional. We studied 385 patients with type 2
      diabetes mellitus, systemic arterial hypertension and dyslipidemia who were
      referred to Otorhinolaryngology Unit with hearing and vestibular symptoms. The
      auditory function was evaluated using conventional tonal audiometry and the
      vestibular function by electronystagmography. Duration of the disease and number
      of comorbidities, hearing thresholds at 125-8000 Hz pure tones, speech
      audiometry, oculomotor evaluation and thermal caloric tests were also analysed.
      RESULTS: A total of 66.7% (95% CI, 61.8-73.4) of patients had 1 comorbidity;
      27.7% (95% CI, 23.3-32.5) had 2 and 5.4% (95% CI, 3.4-8.2) had systemic arterial
      hypertension, diabetes mellitus and dyslipidemia. The mean age was 62 years (SD
      12.9) and 57.1% were women. The majority showed obesity, physical inactivity and
      smoking (77.4%; 95% CI, 72.8-81.4). Cochlear dysfunction was more common than CVD
      (98.9%; 95% CI, 97.3-99.7 versus 36.1%; 95%CI, 31.2-41.1; P=.001). However, the
      presence of CVD was significant in patients over 60 years (chi(2)(tend), P<=.001,
      odds ratio: 6.43) and with MICD >=11 years old (chi(2)(tend), P<=.001, odds
      ratio: 4.57). CONCLUSIONS: Cochlear dysfunction occurs in patients with MICD and
      the impact is greater than that of vestibular dysfunction. However, the age
      factor, duration and number of MICDs contribute to CVD. It is necessary to act on
      the MICDs and lifestyles to improve CVD.

PMID- 22153964
TI  - [The effect of anchor voices and visible speech in training in the GRABS scale of
      perceptual evaluation of dysphonia].
AB  - INTRODUCTION: Perceptual evaluation of voice quality remains a key standard for
      judgment of vocal impairment. The GRABS method has become a commonly-used scale
      for rating severity of dysphonia, but it has no published, standardised protocol
      to follow. Training is important for reaching good interrater agreement for its
      parameters; however, the references most often cited for the GRABS provide no
      guidelines for clinical administration, speech material or rating calibration.
      This study investigated the effect of anchors (standard reference voices) and
      visible speech (narrow band spectrogram) in training non-expert professionals in
      the GRABS method. MATERIAL & METHODS: Four inexperienced listeners evaluated 107
      recorded pathological voices using the GRABS scale in 2 separate sessions; at
      first, without a visible spectrogram and then, 6 months later, with anchors and a
      narrow band spectrogram as additional information. RESULTS: The results show that
      anchors and visible speech helped to improve the reliability of G, B, A and S
      parameters. Interrater agreement according to k statistics was significantly
      stronger with the addition of spectrographic information for rating breathiness
      and strain. DISCUSSION: This study found that non-expert listeners showed
      significant improvement after training with external anchors (standard reference
      voices) and a narrow band spectrogram.

PMID- 22153965
TI  - [Use of desmopressin in children with inherited platelet dysfunctions undergoing
      adenotonsillar procedures].
AB  - INTRODUCTION AND GOALS: Adenotonsillar surgery represents a major haemostatic
      challenge in paediatric patients with mild inherited platelet dysfunction. While
      there are recommendations for perioperative haemostatic management, there are no
      reports of the outcomes with the different recommendations in these children when
      undergoing adenotonsillectomy. Our objective was to evaluate the management of
      perioperative bleeding with desmopressin in children with mild platelet
      dysfunctions who underwent adenotonsillar surgery in our hospital. METHODS: We
      performed a retrospective study aimed at determining the perioperative bleeding
      and complication rate in children with mild inherited platelet dysfunction in
      whom desmopressin was used while undergoing adenotonsillar procedures. RESULTS:
      Between 2004 and 2010, 27 children with mild inherited platelet dysfunction
      underwent adenotonsillar procedures in our hospital and were treated with
      desmopressin. One patient developed perioperative bleeding (3.7%) and there was 1
      child (3.7%) who presented transitory hypotension as a side effect of
      desmopressin. CONCLUSIONS: The use of desmopressin allowed adequate perioperative
      bleeding prophylaxis management in children with mild inherited platelet
      dysfunction who underwent adenotonsillar procedures without presenting severe
      complications.

PMID- 22153966
TI  - Lipid management in high risk coronary patients: how effective are we at
      secondary intervention?
AB  - OBJECTIVE: To assess the proportion of patients who achieve and maintain target
      lipid levels during optimum long term follow up after coronary bypass surgery.
      METHODS: From a prospectively compiled database, we identified 440 patients
      followed for up to 13 years after CABG as part of a radial artery randomised
      controlled trial. All available lipid assays conducted during the follow-up
      period were collected from pathology databases. These were used to calculate the
      annualised mean lipid exposure for each patient. Based upon National Heart
      Foundation guidelines, we determined the proportion of patients whose mean lipid
      exposure attained target levels (total cholesterol <4.0 mmol/L, LDL-C <2.0
      mmol/L, HDL-C >1.0 mmol/L and triglycerides <1.5 mmol/L). This was compared with
      the proportion who had achieved these targets pre-operatively and on their most
      recent cholesterol measurement. RESULTS: 6077 lipid studies (total cholesterol,
      LDL, HDL and triglycerides) in total were obtained. In those who had baseline
      data available, target levels for total cholesterol, HDL-C, LDL-C and
      triglycerides were attained pre-operatively by 16%, 64%, 14% and 39% of patients
      respectively. Annualised mean lipid exposures during up to 13 years of follow up
      for all patients revealed somewhat improved but still suboptimal target
      attainment figures of 24%, 83%, 20% and 53%. The most recent review shows the
      greatest improvement at 47%, 68%, 43% and 62% respectively. Of 141 diabetic
      patients, target attainment was significantly higher for total cholesterol (31%;
      p=0.038) and LDL-C (28%; p=0.006) but lower for HDL-C (75%; p=0.002) and
      triglycerides (40%; p<0.001). CONCLUSION: Despite some improvements seen over
      careful follow up, only HDL-C targets appear attainable for the majority of CABG
      patients. Over half still do not achieve non-HDL national lipid targets.

PMID- 22153967
TI  - Inhibition of homologous recombination by the PCNA-interacting protein PARI.
AB  - Inappropriate homologous recombination (HR) causes genomic instability and
      cancer. In yeast, the UvrD family helicase Srs2 is recruited to sites of DNA
      replication by SUMO-modified PCNA, where it acts to restrict HR by disassembling
      toxic RAD51 nucleofilaments. How human cells control recombination at replication
      forks is unknown. Here, we report that the protein PARI, containing a UvrD-like
      helicase domain, is a PCNA-interacting partner required for preservation of
      genome stability in human and DT40 chicken cells. Using cell-based and
      biochemical assays, we show that PARI restricts unscheduled recombination by
      interfering with the formation of RAD51-DNA HR structures. Finally, we show that
      PARI knockdown suppresses the genomic instability of Fanconi Anemia/BRCA pathway
      deficient cells. Thus, we propose that PARI is a long sought-after factor that
      suppresses inappropriate recombination events at mammalian replication forks.

PMID- 22153968
TI  - A patient with a large pulmonary saddle embolus eluding both clinical gestalt and
      validated decision rules.
AB  - We report a patient with chest pain who was classified as having low risk for
      pulmonary embolism with clinical gestalt and accepted clinical decision rules. An
      inadvertently ordered D-dimer and abnormal result, however, led to the
      identification of a large saddle embolus. This case illustrates the fallibility
      of even well-validated decision aids and that an embolism missed by these tools
      is not necessarily low risk or indicative of a low clot burden.

PMID- 22153969
TI  - Respiratory failure and spontaneous hypoglycemia during noninvasive rewarming
      from 24.7 degrees C (76.5 degrees F) core body temperature after prolonged
      avalanche burial.
AB  - Clinical reports on management and rewarming complications after prolonged
      avalanche burial are not common. We present a case of an unreported combination
      of respiratory failure and unexpected spontaneous hypoglycemia during noninvasive
      rewarming from severe hypothermia. We collected anecdotal observations in a 42
      year-old, previously healthy, male backcountry skier admitted to the ICU at a
      tertiary care center after 2 hours 7 minutes of complete avalanche burial, who
      presented with a patent airway and a core body temperature of 25.0 degrees C
      (77.0 degrees F) on extrication. There was no decrease in core body temperature
      during transport (from 25.0 degrees C [77.0 degrees F] to 24.7 degrees C [76.5
      degrees F]). Atrial fibrillation occurred during active noninvasive external
      rewarming (to 37.0 degrees C [98.6 degrees F] during 5 hours), followed by
      pulmonary edema and respiratory failure (SaO(2) 73% and PaO(2)/FIO(2) 161 mm Hg),
      which resolved with endotracheal intubation and continuous positive end
      respiratory pressure. Moreover, a marked spontaneous glycemic imbalance (from
      22.2 to 1.4 mmol/L) was observed. Despite a possible favorable outcome,
      clinicians should be prepared to identify and treat severe respiratory problems
      and spontaneous hypoglycemia during noninvasive rewarming of severely hypothermic
      avalanche victims.

PMID- 22153970
TI  - Can intra-articular lidocaine supplant the need for procedural sedation for
      reduction of acute anterior shoulder dislocation?

PMID- 22153971
TI  - Performance in appropriate Rh testing and treatment with Rh immunoglobulin in the
      emergency department.
AB  - STUDY OBJECTIVE: The quality measure "Rh immunoglobulin administration for Rh
      negative women at risk for fetal blood exposure" was recently endorsed by the
      National Quality Forum. No published data have shown a related performance gap in
      US emergency departments (EDs). We determine performance in a US ED for
      appropriate Rh testing and treatment among pregnant ED patients at risk of fetal
      blood exposure. METHODS: This was a retrospective, observational study in an
      urban, academic ED with 97,000 annual visits. We performed record review of all
      pregnant ED patients aged 14 to 50 years and presenting between June 1, 2009, and
      June 1, 2010, to determine whether a sensitizing event or a potential sensitizing
      event occurred and whether Rh testing and treatment with Rh immunoglobulin were
      performed when indicated. Performance rates were calculated under 2 different
      assumptions for patients without Rh testing ordered in the ED but who had
      previous data in the electronic medical record: (1) unless explicitly documented
      by the treating physician, previous Rh data were considered as not having been
      checked; and (2) when available in the electronic medical record, Rh status was
      always considered as having been checked. Interrater reliability was assessed for
      whether a trauma represented a sensitizing event. RESULTS: Among 1,465 patients
      identified, 808 met inclusion criteria; 560 had a sensitizing event and 248 had a
      potential sensitizing event. Interrater reliability for determination of
      sensitizing event or potential sensitizing event in trauma was moderate
      (kappa=0.42). Performance rates for Rh testing among patients with sensitizing
      events, with potential sensitizing events, and overall were 73% (95% confidence
      interval [CI] 69% to 76%) (408/560), 36% (95% CI 31% to 43%) (90/248), and 62%
      (95% CI 58% to 65%) (498/808). Appropriate treatment for patients with a
      sensitizing event, with a potential sensitizing event, and overall was 56% (95%
      CI 39% to 71%) (19/34), 0% (95% CI 0% to 49%) (0/5), and 48% (95% CI 33% to 63%)
      (19/39). Assuming that physicians were aware of previous Rh results yielded
      performance rates of 96% (95% CI 93% to 97%) (535/560), 73% (95% CI 67% to 78%)
      (181/248), and 89% (95% CI 86% to 91%) (716/808) and treatment performance rates
      of 54% (95% CI 38% to 69%) (20/37), 0% (95% CI 0% to 30%) (0/11), and 42% (95% CI
      29% to 56%) (20/48). CONCLUSION: In this single-center study, among patients with
      a sensitizing event, performance was moderate for Rh testing and treatment with
      Rh immunoglobulin. Despite lack of consensus or uncertainties in certain measure
      definitions, in at least 1 US academic ED there appears to be an opportunity for
      further evaluation and performance improvement in this area.

PMID- 22153972
TI  - Pilot randomized, controlled trial of pramipexole to augment antipsychotic
      treatment.
AB  - The preferential dopamine D(3)-agonist pramipexole (4.25+/-0.38 mg/day) or
      placebo were added for up to 12 weeks to ongoing antipsychotic treatment for 24
      adult patients with DSM-IV schizophrenia or schizoaffective disorder. Pramipexole
      was generally well-tolerated (82% trial-completion), and yielded greater
      decreases in PANSS-total scores (drug/placebo=2.1; p=0.04), with similar
      decreases in PANSS positive and negative scores and 6.7-fold greater reduction of
      serum prolactin concentrations compared to placebo. There were no differences in
      ratings of mood, cognition or extrapyramidal symptoms, all of which were low at
      intake.

PMID- 22153973
TI  - Early gene mapping after deep brain stimulation in a rat model of tardive
      dyskinesia: comparison with transient local inactivation.
AB  - Deep brain stimulation (DBS) has been extensively used in Parkinson's disease and
      is also currently being investigated in tardive dyskinesia (TD), a movement
      disorder induced by chronic treatment with antipsychotic drugs such as
      haloperidol (HAL). In rodents, vacuous chewing movements (VCMs) following chronic
      HAL administration are suggested to model orofacial dyskinesias in TD. We show
      that 60 min of DBS (100 MUA, 90 MUs, 130 Hz) applied to the entopeduncular (EPN)
      or subthalamic (STN) nuclei significantly decreases HAL-induced VCMs. Using
      zif268 as a neural activity marker, we found that in HAL-treated animals EPN
      stimulation increased zif268 mRNA levels in the globus pallidus (+65%) and
      substantia nigra compacta (+62%) and reticulata (+76%), while decreasing levels
      in the motor cortex and throughout the thalamus. In contrast, after STN DBS
      zif268 levels in HAL-treated animals decreased in all basal ganglia structures,
      thalamus and motor cortex (range: 29% in the ventrolateral caudate-putamen to
      100% in the EPN). Local tissue inactivation by muscimol injections into the STN
      or EPN also reduced VCMs, but to a lesser degree than DBS. When applied to the
      EPN muscimol decreased zif268 levels in substantia nigra (-29%), whereas STN
      infusions did not result in significant zif268 changes in any brain area. These
      results confirm the effectiveness of DBS in reducing VCMs and suggest that tissue
      inactivation does not fully account for DBS effects in this preparation. The
      divergent effects of STN vs. EPN manipulations on HAL-induced zif268 changes
      suggest that similar behavioral outcomes of DBS in these two areas may involve
      different neuroanatomical mechanisms.

PMID- 22153974
TI  - Quantification of the GH/IGF-axis components: lessons from human studies.
AB  - Originally, the circulating bioactivity of IGF-I was estimated by bioassays
      measuring the ability of serum to stimulate uptake of labeled sulfate or
      thymidine in cultures of costal cartilage or by the ability of serum to stimulate
      the uptake of glucose in fat tissue cultures. However, because of their laborious
      and unspecific nature, the original bioassays were quickly abandoned with the
      development of the first RIA for IGF-I in 1977. Consequently, for the past three
      decades the endogenous IGF-I bioactivity has been almost exclusively estimated by
      the use of immunoassays. Beyond any doubt, the immunoassays have provided an
      extensive insight into IGF-I physiology and pathophysiology. However,
      immunoassays ignore the presence of the IGFBPs, which are important regulators of
      IGF-I action in vivo. In addition, immunoassays do not consider the presence of
      IGF-II, which also interacts with the IGF-I receptor (IGF-IR). This aroused our
      interest to reintroduce the bioassay; therefore, we established a cell-based
      kinase receptor activation (KIRA) assay based on cells transfected with the human
      IGF-IR. The output signal of the KIRA assay is IGF-IR phosphorylation, and, as
      such, it is highly specific. Further, because detection of phosphorylated IGF-IRs
      is based on modern immunoassay techniques, the overall performance of the assay
      is close to that of a traditional IGF-I immunoassay. The first part of this
      review comprises a short description of the bioassay, and a more in-depth
      presentation of the data that have been obtained so far. It will be demonstrated
      that the bioassay is indeed able to yield novel information on the IGF system,
      most likely because it is able to integrate the different components of the IGF
      system into one signal: IGF-IR activation. As IGF-I, circulating GH is bound to
      larger proteins, the far most important GH-binding protein (GHBP) is identical to
      the extracellular domain of the GH receptor (GHR). Because of its origin, GHBP
      binds GH with the same affinity as GHR and, consequently, GHBP may affect GH
      bioactivity as well as pharmacokinetics. To improve our knowledge on the complex
      interaction between GH and GHBP in vivo, we found it of interest to develop a
      method for determination of free GH. To this end, we developed an ultrafiltration
      assay that enabled isolation of free GH in undiluted serum during approached in
      vivo-like conditions. The last part of this review presents our current data on
      free GH and its interaction with GHBP.

PMID- 22153975
TI  - Fltp(T2AiCre): a new knock-in mouse line for conditional gene targeting in
      distinct mono- and multiciliated tissues.
AB  - We recently identified Flattop (Fltp; 1700009p17Rik) in a screen for potential
      Foxa2 target and novel mouse organizer genes. Besides its expression in the
      embryonic node, we found that Fltp is active in other monociliated tissues such
      as the sensory organs of the inner ear, duct and islets of the pancreas as well
      as in testis. Additionally, Fltp mRNA is expressed in multiciliated epithelial
      cells of the lung and of the choroid plexi in the brain. To genetically lineage
      trace these cells during development and injury as well as to conditionally
      inactivate genes in these tissues, we generated a Cre recombinase knock-in mouse
      line using the Fltp gene locus. By homologous recombination we have fused the
      Fltp open-reading frame to a tandem affinity purification (TAP) tag followed by
      an intervening viral T2A sequence for co-translational cleavage and an improved
      Cre recombinase (iCre). This strategy allows both the analysis of the tagged Fltp
      TAP-T2A protein and the usage of the iCre recombinase for conditional targeting
      approaches. Using the ROSA26 reporter mouse line we show that Fltp(T2AiCre) is
      first active in the monociliated cells of the node, notochord, floorplate and
      prechordal plate, consistent with the Fltp-TAP-T2A protein production in the node
      progenitor cells. Furthermore iCre recombinase activity is detected in
      multiciliated tissues such as choroid plexi of the brain and epithelial cells of
      the lung with the onset at E10.5 and E13.5, respectively. In the pancreas, beta
      galactosidase activity is seen in the monociliated cells of the pancreatic duct
      and islet of Langerhans. Intercrossing Fltp(T2AiCre) mice with the CAG-CAT-EGFP
      reporter mouse line further confirms iCre activity in multiciliated cells of the
      lung and brain on a cellular level. Thus, the Fltp(T2AiCre) line is a powerful
      tool to conditionally inactivate genes in distinct mono- and multiciliated
      tissues and to analyze the tagged Fltp protein in vivo.

PMID- 22153977
TI  - Immune profiling of Alzheimer patients.
AB  - Alzheimer's disease (AD) is characterized by extracellular senile plaques in the
      brain, containing amyloid-beta peptide (Abeta). We identify immunological
      differences between AD patients and age-matched controls greater than those
      related to age itself. The biggest differences were in the CD4+ rather than the
      CD8+ T cell compartment resulting in lower proportions of naive cells, more late
      differentiated cells and higher percentages of activated CD4+CD25+ T cells
      without a Treg phenotype in AD patients. Changes to CD4+ cells might be the
      result of chronic stimulation by Abeta present in the blood. These findings have
      implications for diagnosis and understanding the aetiology of the disease.

PMID- 22153976
TI  - Endogenous cytosolic Ca(2+) buffering is necessary for TRPM4 activity in cerebral
      artery smooth muscle cells.
AB  - The melastatin transient receptor potential (TRP) channel, TRPM4, is a critical
      regulator of smooth muscle membrane potential and arterial tone. Activation of
      the channel is Ca(2+)-dependent, but prolonged exposures to high global Ca(2+)
      causes rapid inactivation under conventional whole-cell patch clamp conditions.
      Using amphotericin B perforated whole cell patch clamp electrophysiology, which
      minimally disrupts cytosolic Ca(2+) dynamics, we recently showed that Ca(2+)
      released from 1,2,5-triphosphate receptors (IP(3)R) on the sarcoplasmic reticulum
      (SR) activates TRPM4 channels, producing sustained transient inward cation
      currents (TICCs). Thus, Ca(2+)-dependent inactivation of TRPM4 may not be
      inherent to the channel itself but rather is a result of the recording
      conditions. We hypothesized that under conventional whole-cell configurations,
      loss of intrinsic cytosolic Ca(2+) buffering following cell dialysis contributes
      to inactivation of TRPM4 channels. With the inclusion of the Ca(2+) buffers
      ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA, 10mM) or
      bis-ethane-N,N,N',N'-tetraacetic acid (BAPTA, 0.1mM) in the pipette solution, we
      mimic endogenous Ca(2+) buffering and record novel, sustained whole-cell TICC
      activity from freshly-isolated cerebral artery myocytes. Biophysical properties
      of TICCs recorded under perforated and whole-cell patch clamp were nearly
      identical. Furthermore, whole-cell TICC activity was reduced by the selective
      TRPM4 inhibitor, 9-phenanthrol, and by siRNA-mediated knockdown of TRPM4. When a
      higher concentration (10mM) of BAPTA was included in the pipette solution, TICC
      activity was disrupted, suggesting that TRPM4 channels on the plasma membrane and
      IP(3)R on the SR are closely opposed but not physically coupled, and that
      endogenous Ca(2+) buffer proteins play a critical role in maintaining TRPM4
      channel activity in native cerebral artery smooth muscle cells.

PMID- 22153978
TI  - Salivary cortisol and frailty syndrome in elderly residents of long-stay
      institutions: a cross-sectional study.
AB  - Analyze the relationship between frailty and cortisol in elderly residents of
      long-stay institutions. A cross-sectional study was conducted in the city of Joao
      Pessoa-PB-Brazil, on a sample of residents of long-stay institutions. Data were
      collected on frailty phenotype (weight loss, fatigue, slowness, weakness and low
      physical activity) and salivary cortisol (first measurement between 6 and 7a.m.;
      second measurement between 11 and 12a.m.; third measurement between 4 and 5p.m.).
      Statistical analysis applied Pearson's correlation test, Chi-square test, ANOVA
      and linear regression. The sample was composed of 69 elderly subjects, 37.7% men
      and 62.3% women, with a mean age of 77.5 (+/-7.8) years. The percentage of frail
      elderly was 45.8%. Frail aged subjects achieved higher cortisol values on the
      third measurement (p=0.04) and frailty load was significantly associated to the
      first measurement (r=0.25, p=0.04). Simple linear regression analysis showed a
      rate of determination (R(2)=0.05) between frailty load and the first cortisol
      measurement. Greater cortisol values in the morning and before bed among frail
      aged individuals suggest a positive correlation may exist between cortisol levels
      and frailty in elderly residents of long-stay institutions.

PMID- 22153979
TI  - Gender and the functional outcome of elderly ischemic stroke patients.
AB  - The purpose of this study was to investigate the effect of gender on the
      functional outcome after ischemic stroke. In a retrospective chart review we
      studied 919 survivors of ischemic stroke admitted for rehabilitation at a
      geriatric rehabilitation ward of a university affiliated hospital. Functional
      outcome of female and male patients was assessed by Functional Independence
      Measurement (FIM) at admission and discharge. Data were analyzed by t test, Chi
      square test and Linear Regression. A total number of 919 patients were admitted
      of whom 56% were males. A higher proportion of male patients reported ischemic
      heart disease (p<0.001), hypercholesterolemia (p=0.035), Parkinson's disease
      (p=0.044), and previous stroke (p<0.001). Males had also higher Mini-Mental State
      Examination (MMSE) scores (p<0.001). Total FIM at admission (62.54 +/- 25.98 and
      66.00 +/- 25.49; p=0.043), and total FIM at discharge (80.39 +/- 30.35 and 85.59
      +/- 29.08; p=0.008), motor FIM at admission (40.04 +/- 18.89 and 42.51 +/- 18.47;
      p=0.047) and motor FIM at discharge (56.41 +/- 23.04 and 60.44 +/- 21.84;
      p=0.007) were higher among male patients. However, a trend for a borderline
      statistical difference was observed for FIM gains upon discharge between men and
      women. A multiple linear regression analysis showed that total FIM at discharge
      was neither associated with male nor female gender (beta=-0.009; p=0.69). The
      findings suggest that the functional outcome of male survivors presenting for
      rehabilitation after acute ischemic stroke is slightly better. After adjusting
      for possible covariates, gender did not emerge as an independent predictor for
      higher FIM at discharge, suggesting that gender should not be held as adversely
      affecting rehabilitation of such patients.

PMID- 22153980
TI  - An evaluation of potential allelic association between the STRs vWA and D12S391:
      implications in criminal casework and applications to short pedigrees.
AB  - An evaluation was carried out to determine the effect on routine forensic
      calculations when incorporating STRs D12S391 and vWA. These loci are co-located
      on the same arm of chromosome 12. It has been suggested that allelic association
      could result in over-estimates of strength-of-evidence calculations. In the first
      place, we argue that is very unlikely that genotypes collected from typical
      cosmopolitan forensic databases can provide meaningful information about effects
      attributable to physical linkage. Since admixture is the most likely cause of
      allelic association in modern populations we specifically evaluate this effect.
      We use computer simulation as the preferred approach to generate populations with
      disequilibrium and observe the effect on match probability. Although we have
      specifically evaluated the linkage between D12S391 and vWA, the methods described
      in this paper can be extended and generalized to evaluate linkage effects between
      any pair of loci where the recombination rate is known. Many jurisdictions apply
      a subpopulation correction following the standard method of Balding and Nichols.
      Such corrections would appear to be more than adequate to compensate for any
      increase in match probability that we were able to create by this admixture.
      Linkage is likely to have an appreciable effect on relatedness calculations in
      short pedigrees in some but not all instances. We examined those circumstances
      where an effect is likely and give formulae for some common situations. The
      complexity of these calculations is a cause for concern in some laboratories. We
      discuss possible strategies that might be employed and plausible effects.

PMID- 22153981
TI  - The state of therapy for removal of alloantibody producing plasma cells in
      transplantation.
AB  - The current evidence clearly points towards donor specific alloantibody as a
      major cause of allograft loss. In order to mitigate allograft loss due to
      antibodies, treating the source of antibody production, the plasma cell is
      essential. Therapies that lack effect on the terminally differentiated (long
      lived) plasma cell, such as rituximab, intravenous immune globulin and,
      plasmapheresis were the therapies used prior to 2007. In studies, their ability
      to remove antibody was found to be incomplete and/or cost prohibitive. In 2007, a
      proteasome inhibitor, bortezomib, was used for the first time in transplant due
      to its ability to deplete plasma cells. Through multiple case reports it has
      demonstrated consistent success in DSA reduction and removal, with only a few
      reports of failure to date. This review discusses the plasma cell, the
      alloantibody, and the current data supporting proteasome inhibitor use in
      transplant.

PMID- 22153982
TI  - Structured sparse linear graph embedding.
AB  - Subspace learning is a core issue in pattern recognition and machine learning.
      Linear graph embedding (LGE) is a general framework for subspace learning. In
      this paper, we propose a structured sparse extension to LGE (SSLGE) by
      introducing a structured sparsity-inducing norm into LGE. Specifically, SSLGE
      casts the projection bases learning into a regression-type optimization problem,
      and then the structured sparsity regularization is applied to the regression
      coefficients. The regularization selects a subset of features and meanwhile
      encodes high-order information reflecting a priori structure information of the
      data. The SSLGE technique provides a unified framework for discovering structured
      sparse subspace. Computationally, by using a variational equality and the
      Procrustes transformation, SSLGE is efficiently solved with closed-form updates.
      Experimental results on face image show the effectiveness of the proposed method.

PMID- 22153983
TI  - Results of molecular docking as descriptors to predict human serum albumin
      binding affinity.
AB  - Pharmacokinetic properties of a compound are important in drug discovery and
      development. These properties are most often estimated from the structural
      properties of a compound with a structural-activity relationship (QSAR) approach.
      Rapid advances in molecular pharmacology have characterized a number of important
      proteins that shape the pharmacokinetic profile of a compound. Previous studies
      have shown that molecular docking, which is capable of analyzing compound-protein
      interactions, could be applied to make a categorical estimation of a
      pharmacokinetic property. The present study focused on the binding affinity of
      human serum albumin (HSA) as an example to show that docking descriptors might
      also be useful to estimate the exact value of a pharmacokinetic property. A
      previously reported dataset containing 94 compounds with logK(HSA) values was
      analyzed. A support vector regression model based on the docking descriptors was
      able to approximate the observed logK(HSA) in the training and validation dataset
      with an R(2)=0.79. This accuracy was comparable to known QSAR models based on
      compound descriptors. In this case study, it was shown that an account of protein
      flexibility is essential to calculate informative docking descriptors for use in
      the quantitative estimation of logK(HSA).

PMID- 22153984
TI  - The low attenuation area on dual-energy perfusion CT: correlation with the
      pulmonary function tests and quantitative CT measurements.
AB  - PURPOSE: To retrospectively investigate the distribution of the low attenuation
      area (LAA) on dual energy perfusion CT (DEpCT) in comparison with the results of
      pulmonary function tests (PFTs) and quantitative CT measurements. MATERIALS AND
      METHODS: Twenty-eight patients (15 male and 13 female; mean age: 62.21 years)
      underwent DEpCT and PFTs within a 1-month interval. The ranges of the LAA on
      DEpCT were classified into six groups with attenuation values of 0-3, 0-5, 0-8, 0
      10, 0-13 and 0-15 HU and the ratios of LAA in each group were compared with the
      percentage of forced expiratory volume in the 1st second (%FEV(1.0)),
      FEV(1.0)/forced vital capacity (FEV(1.0)/FVC) and the relative area of the lung
      with attenuation coefficients lower than -950 HU (RA(-950)). RESULTS: The LAAs on
      the DEpCT images were significantly correlated with the RA(-950), %FEV(1.0) and
      FEV(1.0)/FVC, and the regression analysis showed that the best values of LAA on
      DEpCT were 0-10 HU with RA(-950) (r=0.63), 0-8 HU with %FEV(1.0) (r=-0.52) and 0
      8HU with FEV(1.0)/FVC (r=-0.61) per patient. CONCLUSION: The iodine disturbance
      on DEpCT had a moderate correlation with the results of the PFTs and RA(-950),
      but further examination would be needed for evaluation of iodine distribution.

PMID- 22153985
TI  - Apoptosis, cell proliferation and vitellogenesis during the folliculogenesis and
      follicular growth in teleost fish.
AB  - Aiming to better understand folliculogenesis, this study evaluated cell death and
      proliferation of ovarian cells, besides cathepsin-D expression in Prochilodus
      argenteus captured in two sites of the Sao Francisco River downstream from the
      Tres Marias Dam, Brazil. In the site immediately following the Dam (S1), low
      levels of dissolved oxygen were registered in the rainy period. The water
      temperature was higher in the Sao Francisco River immediately after the
      confluence with the Abaete River (S2), regardless of the period. In S1, the
      ovaries showed smaller oocytes, high caspase-3 enzymatic activity and apoptosis,
      lower cells in proliferation and GSI, as well as a lesser quantity of cathepsin-D
      when compared to females captured from S2. Regarding relative frequency of
      ovarian structures, in the dry period, only oogonia and perinucleolar oocytes
      were found in fish ovaries from both sites. On the other hand, in the rainy
      period, the relative frequency of oogonia and perinucleolar oocytes decreased and
      the vitellogenic oocytes increased in S2. Postovulatory follicles were observed
      only in S2, whereas atretic follicles occurred at a higher frequency in S1. Our
      results showed that apoptosis, cell proliferation and cathepsina-D evaluation can
      be used as biomarkers of environmental impact.

PMID- 22153986
TI  - Management of endometrial polyps diagnosed before or during ICSI cycles.
AB  - This retrospective study aimed to shed light on the management options of
      endometrial polyps diagnosed before or during intracytoplasmic sperm injection
      (ICSI) treatment. The study included all fresh ICSI cycles performed in the
      Anatolia IVF Center between July 2005 and January 2009. Group 1 consisted of 47
      patients who were diagnosed with an endometrial polyp before their ICSI cycle.
      All patients diagnosed with an endometrial polyp by transvaginal ultrasonography
      before the ICSI cycle underwent hysteroscopic polyp resection. Group 1 was
      compared with 47 matched control patients without endometrial polyps who
      underwent standard ICSI cycles (group 2). Group 3 included 128 patients diagnosed
      with an endometrial polyp during stimulation in their ICSI cycles. Group 3 was
      compared with 128 matched control patients without endometrial polyps who
      underwent standard ICSI cycles (group 4). Patients diagnosed with an endometrial
      polyp before ICSI cycles were similar to their controls with regard to clinical
      pregnancy (29.8% versus 38.3%) and live-birth (25.5% versus 31.9%) rates per
      transfer, as were patients diagnosed with an endometrial polyp during ovarian
      stimulation (clinical pregnancy rates 45.3% versus 46.9%; live-birth rates 40.6%
      versus 39.8%). In conclusion, further studies are required to identify the most
      appropriate management of endometrial polyps.

PMID- 22153987
TI  - Density, calibre and ramification of muscle capillaries are altered in a mouse
      model of severe spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is traditionally described and characterised as a
      disease of the neuromuscular system. Recently, the vascular system has been
      implicated in SMA pathogenesis, but there are no reports on whether this impacts
      on skeletal muscle microvasculature. Using an established mouse model of severe
      SMA (Smn(-/-);SMN2(+/+)), we examined the capillary bed in three different
      skeletal muscles using quantitative imaging and western blotting in late
      symptomatic mice (P5). We found a dramatic (45%) decrease in the density of the
      capillary bed in all muscles examined compared to littermate controls at early
      and late symptomatic time points, and reduced expression of a key endothelial
      protein, PECAM-1. In addition, capillary calibre was increased by 50% in SMA mice
      while ramification of capillaries into muscle was reduced. Investigation of
      earlier developmental time points revealed identical changes at an early
      symptomatic time point (P3), but significantly, no difference at a pre
      symptomatic time point (P1). These changes are likely to have considerable impact
      on the ability of the muscle capillary bed to deliver oxygen and remove
      metabolites from muscle and may therefore contribute to pathogenesis in SMA.

PMID- 22153988
TI  - Correlation between muscle involvement, phenotype and D4Z4 fragment size in
      facioscapulohumeral muscular dystrophy.
AB  - This study aimed to evaluate muscle involvement pattern and correlate the lesions
      on muscle imaging with clinical features and D4Z4 fragment size in 24 patients
      with facioscapulohumeral muscular dystrophy (FSHD). The grading of the muscle
      image detected by computed tomography (CT) was based on a four-point semi
      quantitative visual scale. On muscle CT, the most affected muscle was trapezium,
      followed by hamstrings. CT image identified hamstrings involvement rather than
      shoulder-girdle in clinically asymptomatic subjects. CT image also showed that
      axial muscle was affected in one-third of patients which appeared even earlier
      than clinical manifestation. Strong correlations between CT findings, serum
      creatine kinase level and clinical severity scores were also found. Asymmetric
      involvement was more evident on CT image than it identified in manual muscle
      strength testing. Inverse correlation between CT grade and D4Z4 fragment size was
      clearly demonstrated. These findings suggest muscle CT will be helpful for the
      process of early intervention in FSHD, even in subjects in a preclinical status.

PMID- 22153989
TI  - Focal myositis--neurogenic phenomenon?
AB  - We report four cases of focal myositis. The patients, three men and one woman,
      had painful muscle hypertrophy, affecting four different sites. MRI confirmed the
      muscle enlargement and oedema. Electromyography revealed evidence of acute and
      chronic denervation in all four cases. Muscle biopsy was available in three and
      confirmed features suggestive of focal myositis. Based on our patient material,
      we suggest that chronic nerve irritation, such as compression, can lead to muscle
      hypertrophy which, when prolonged, provokes fibre necrosis and secondary
      inflammation. Our finding in four patients having hypertrophy involving four
      different sites, leads us further to suggest that this may be the common
      mechanism behind focal myositis.

PMID- 22153990
TI  - X-linked myotubular myopathy due to a complex rearrangement involving a
      duplication of MTM1 exon 10.
AB  - X-linked myotubular myopathy is a predominantly severe congenital myopathy with
      central nuclei on muscle biopsy due to mutations in the MTM1 gene encoding
      myotubularin. We report a boy with typical features of X-linked myotubular
      myopathy. Sequencing of the MTM1 gene did not reveal any causative mutations.
      Subsequent MLPA analysis identified a duplication of MTM1 exon 10 both in the
      patient and his mother. Additional quantitative fluorescent PCR and long-range
      PCR revealed an additional large deletion (2536bp) within intron 10, 143bp
      downstream of exon 10, and confirmed the duplication of exon 10. Our findings
      suggest that complex rearrangements have to be considered in typically affected
      males with X-linked myotubular myopathy.

PMID- 22153991
TI  - 5th Annual Dysferlin Conference 11-14 July 2011, Chicago, Illinois, USA.

PMID- 22153993
TI  - Transcription of pattern recognition receptors and abortive agents induced
      chemokines in the bovine pregnant uterus.
AB  - Pattern recognition receptors (PRRs) are important components of the innate
      immune system whose ligands are specific pathogen associated molecular patterns
      (PAMPs). Considering the scarcity of studies on transcription of PRRs in the
      pregnant uterus of cows, and its response to PAMPs and microorganisms that cause
      abortion in cattle, this study aimed to characterize the transcription of TLR1
      10, NOD1, NOD2 and MD2 in bovine uterus throughout gestation and to investigate
      the sensitivity of different uterine tissues at third trimester of pregnancy to
      purified TLR ligands or heat-killed Brucella abortus, Salmonella enterica
      serotype Dublin (S. Dublin), Listeria monocytogenes, and Aspergillus fumigatus,
      by assessing chemokine transcription. RNA extracted from endometrium, placentome
      and intercotiledonary region of cows at the first (n=6), second (n=6), and third
      (n=6) trimesters of pregnancy were subjected to real time RT-PCR. After
      stimulation of endometrium and intercotiledonary regions with purified TLR
      ligands or heat-killed microorganisms, gene transcription was assessed by real
      time RT-PCR. In the placentome, there was no significant variation in TLRs
      transcription throughout the three trimesters of pregnancy. In the endometrium,
      there was significant variation in TLR4 and TLR5 transcription during the three
      stages of gestation; i.e. TLR4 transcription was higher during the third
      trimester, whereas TLR5 transcription was higher during the last two trimesters.
      In the intercotiledonary region, there was significant variation in transcription
      of TLR1/6, TLR7, and TLR8, which were more strongly expressed during the first
      trimester of pregnancy. At the third trimester of gestation, significant
      transcription of CXCL6 and CXCL8 was detected mostly in endometrial tissues in
      response to purified TLR4 and TLR2 ligands. Transcription of these chemokines was
      induced in the endometrium and intercotiledonary region at the third trimester of
      pregnancy when stimulated with heat-killed B. abortus or S. Dublin. Therefore,
      this study demonstrates that some PRRs are expressed in the uterus during
      pregnancy, which coincides with its ability to respond to stimulation with TLRs
      ligands as well as heat-killed organisms known to cause abortion in cattle.

PMID- 22153994
TI  - Identification and validation of bioactive small molecule target through
      phenotypic screening.
AB  - For effective bioactive small molecule discovery and development into new
      therapeutic drug, a systematic screening and target protein identification is
      required. Different from the conventional screening system, herein phenotypic
      screening in combination with multi-omics-based target identification and
      validation (MOTIV) is introduced. First, phenotypic screening provides visual
      effect of bioactive small molecules in the cell or organism level. It is
      important to know the effect on the cell or organism level since small molecules
      affect not only a single target but the entire cellular mechanism within a cell
      or organism. Secondly, MOTIV provides systemic approach to discover the target
      protein of bioactive small molecule. With the chemical genomics and proteomics
      approach of target identification methods, various target protein candidates are
      identified. Then network analysis and validations of these candidates result in
      identifying the biologically relevant target protein and cellular mechanism.
      Overall, the combination of phenotypic screening and MOTIV will provide an
      effective approach to discover new bioactive small molecules and their target
      protein and mechanism identification.

PMID- 22153995
TI  - A case report of surgically treated drug resistant epilepsy associated with
      subependymal nodular heterotopia.
AB  - Subependymal nodular heterotopia (SNH) is a cortical development malformation
      that is commonly associated with medically resistant epilepsy. Cases of SNH are
      challenging to treat surgically because there are typically multiple nodules,
      which may be involved in epileptogenesis. Moreover, dual pathology may exist in
      these patients. Here, we present a case with unilateral subependymal heterotopic
      nodules associated with ipsilateral hippocampal atrophy. Invasive and non
      invasive work-ups revealed that the hippocampus was the actual ictal onset zone
      and that the SNH was not involved. An anterior temporal lobectomy was carried
      out, and postoperative seizure outcome was class Ia at the end of 2 years. The
      case demonstrates that SNH may not play a major role in patients with dual
      pathology. However, direct electroencephalography (EEG) recording from areas of
      SNH and other possible epileptogenic regions is indispensable in defining the
      ictal onset zone and avoiding poor surgical outcomes.

PMID- 22153996
TI  - Does resuscitation with albumin-containing solutions improve mortality in sepsis?

PMID- 22153997
TI  - Stress-induced cardiomyopathy caused by heat stroke.
AB  - Heat stroke is defined by central nervous system abnormalities and failure of
      proper maintenance of thermoregulation as a result of high core body temperature
      ensuing from exposure to high environmental temperatures or strenuous exercise.
      Common complications include acute respiratory distress syndrome, disseminated
      intravascular coagulation, acute renal injury, hepatic injury, and
      rhabdomyolysis. Myocardial injury may also occur during heat stroke, resulting in
      cardiac enzyme increase and ST-segment changes on the ECG. Such findings might
      behave as diagnostic pitfalls by mimicking the presentation of coronary artery
      occlusive myocardial infarction. A previous case report described a patient with
      heat stroke and ST-segment elevation, in which the definite cause of the ST
      segment elevation was unclear; however, acute myocardial infarction caused by
      coronary artery disease was ruled out according to the clinical signs, serial ECG
      changes, and serum level of cardiac biomarkers. Stress-induced cardiomyopathy
      (Takotsubo cardiomyopathy) was suspected, but it could not be confirmed because
      of the lack of coronary angiography. We herein report a case of heat stroke
      presenting with ST-segment elevation and cardiogenic shock. Coronary angiography
      was performed and coronary artery occlusive myocardial infarction was ruled out
      because of the presence of patent coronary arteries. Left ventriculography showed
      midventricular and apical hypokinesis, and stress-induced cardiomyopathy was then
      determined to be the appropriate diagnosis. Heat stroke causes increase of serum
      catecholamine levels, in which oversecretion and abnormal responses to
      catecholamines are a possible cause of stress-induced cardiomyopathy.
      Catecholamines may therefore be the key in linking heat stroke and stress-induced
      cardiomyopathy.

PMID- 22153998
TI  - Pharmacologic prophylaxis for acute mountain sickness: a systematic shortcut
      review.
AB  - STUDY OBJECTIVE: Multiple studies have explored pharmacologic interventions to
      prevent acute mountain sickness. A systematic review of this subject published in
      2000 found that both acetazolamide and dexamethasone were effective. Since 2000,
      a number of other agents have been reported to be beneficial. This EBEM review
      evaluates the most current evidence on this topic. METHODS: We searched MEDLINE,
      EMBASE, the Cochrane Central Register of Controlled Trials, SPORTDiscus,
      Emergency Medical Abstracts, and ClinicalTrials.gov from 2000 to July 2011. Only
      randomized placebo-controlled trials with an N greater than or equal to 50 and
      systematic reviews were reviewed. Standard criteria for assessing trial quality
      were independently assessed by 2 authors. RESULTS: Seven hundred eighty-six
      citations were retrieved, of which 105 were reviewed in their entirety. Eleven
      randomized controlled trials and 1 systematic review appeared to meet inclusion
      criteria; however, 4 randomized controlled trials were excluded for high risk of
      bias. The remaining 7 randomized controlled trials investigated antioxidants,
      magnesium, sumatriptan, gabapentin, acetazolamide, and Ginkgo biloba. No trials
      studying dexamethasone met our criteria. Acetazolamide was associated with a
      reduction in acute mountain sickness symptoms, with a number needed to treat
      ranging from 8 to 3 among 3 trials and at doses ranging from 250 to 750 mg daily.
      Sumatriptan showed benefit in 1 trial (number needed to treat=4), as did
      gabapentin (number needed to treat=6). Antioxidants, magnesium, and G biloba were
      not efficacious. Reported adverse events included somnolence with gabapentin and
      paresthesias with acetazolamide. The systematic review affirmed our results but
      did not capture trials studying antioxidants, magnesium, sumatriptan, or
      gabapentin. CONCLUSION: Acetazolamide is effective for the prevention of acute
      mountain sickness but may be associated with paresthesias. Sumatriptan and
      gabapentin are beneficial but require further study.

PMID- 22153999
TI  - Blood mercury levels among fish consumers residing in areas with high
      environmental burden.
AB  - Mercury is a ubiquitous, persistent toxicant found in the environment. In water,
      mercury bioaccumulates up the food chain and leads to high concentrations in
      fish. Consumption of contaminated fish is the major source of exposure to mercury
      in the US. The objective of this study was to enroll persons living in areas
      selected by the Environmental Protection Agency (EPA) to have high mercury
      concentrations and who consume at least 6o z of locally caught fish per week to
      determine the feasibility of monitoring future trends among a population
      identified as highly exposed. Blood samples were collected at time of interview
      and analyzed for mercury. Participants (n=287) were enrolled from North Carolina,
      Maryland, and South Dakota. Participants reported eating an average of five
      servings of fish per week. The overall geometric mean for total mercury was 0.75
      MUg L(-1), with North Carolina having the highest mean level (2.02 MUg L(-1)).
      Overall, 42% of the study population had levels greater than the US geometric
      mean 0.83 MUg L(-1). The number of servings of fish consumed was not found to be
      associated with blood mercury levels. We were able to identify some persons with
      elevated mercury concentrations living in areas identified by EPA; however,
      identifying and monitoring a highly exposed population over time would be
      challenging.

PMID- 22154000
TI  - Biosorption of thorium on the external shell surface of bivalve mollusks: the
      role of shell surface microtopography.
AB  - External shell surface (ESS) of bivalve mollusks is known to adsorb various
      metals dissolved in ambient water in high concentration. It is hypothesized here
      that the surface microtopography of the thin organic coating layer, periostracum,
      or calcareous shell (if periostracum was destroyed) plays a major role in the
      adsorption of actinides on ESS. Thorium (natural alpha-emitter) was used in short
      term biosorption experiment with shell fragments of five bivalve mollusks. After
      a 72 h exposure to Th (~6 kBq L(-1)), thorium concentration was measured on ESS
      using laser ablation inductively coupled plasma mass spectrometry; the
      distribution and density of alpha tracks were subsequently visualized by alpha
      track autoradiography. A trend in reduced Th concentrations on the ESS was
      observed depending upon the species tested: (group 1 ~4000 MUg g(-1)) Chlamys
      islandica (M.), Mercenaria mercenaria (L.), Dreissena polymorpha (P.)>(group 2
      ~1200 MUg g(-1)) Crassostrea virginica (G.)?(group 3 ~150 MUg g(-1)) Mytilus
      edulis L. The microtopography of ESS was characterized by scanning electron
      microscopy revealing the high porosity of the calcareous surface of C. islandica
      and M. mercenaria, lamellate surface of periostracum in D. polymorpha, uneven but
      a weakly porous surface of periostracum of C. virginica, and a nearly smooth
      surface of the periostracum of M. edulis. This work has demonstrated, for the
      first time, the presence of a strong correlation between concentration of
      adsorbed Th and ESS microtopography, and the role of the periostracum in this
      process is discussed.

PMID- 22154001
TI  - Challenges in assessing the toxic effects of polycyclic aromatic hydrocarbons to
      marine organisms: a case study on the acute toxicity of pyrene to the European
      seabass (Dicentrarchus labrax L.).
AB  - The acute toxicity (96 h) of pyrene (PY) to European seabass (Dicentrachus
      labrax) juveniles assessed in a semi-static bioassay (SSB) with medium renewal at
      each 12h, and in a static bioassay (SB) without medium renewal was compared in
      laboratorial conditions (water PY concentrations: 0.07-10 mg L(-1)). Main
      findings in the SSB that assessed mainly the toxicity of PY and its metabolites
      were: increased levels of bile PY metabolites in good agreement with the profile
      of lipid peroxidation levels (LPO) in exposed fish relating PY exposure and
      oxidative damage; increased levels of PY-type compounds in the brain indicating
      their ability to cross the blood-brain barrier; increased levels of these
      substances in liver and muscle which are edible tissues for humans thus raising
      concern on potential adverse effects on consumers of fish from PY contaminated
      areas; a significant inhibition of glutathione S-transferase activity suggesting
      its involvement in PY detoxication as toxicant scavenger; finally, an almost
      complete impairment of the swimming velocity at all the PY concentrations linking
      sub-individual to higher population level effects. In the SB, where the overall
      toxicity of PY, its metabolites and environmental degradation products was
      evaluated, 19% and 79% of PY decay in test media was found at 12 and 96 h,
      respectively. In general, the effects were similar to those of SSB but with
      significant effects being induced at higher PY concentrations indicating that the
      parental compound is more toxic than its environmental degradation products. The
      other main differences relatively to the SSB were: increased levels of PY-type
      substances in the liver suggesting more accumulation in this organ. Therefore,
      these findings highlight the need of carefully considering experimental design
      options when assessing the toxicity of readily degradable substances to marine
      fish, and stress the importance of taking into consideration the toxicity of
      environmental degradation products in addition to toxic effects of the parental
      substance and its metabolites for marine ecological risk assessment.

PMID- 22154002
TI  - Occurrence of uranium in Swiss drinking water.
AB  - The results of a nationwide survey of uranium in Swiss drinking water are
      reported. Elevated concentrations of uranium in groundwater are found mainly in
      the alpine regions and can be traced back to the geology of the bedrock. Water
      sources were systematically surveyed and analysed for the presence of Li, B, Si,
      Sc, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Cd, Sn, Sb, Ba, Tl, Pb and U and
      the results were analysed to determine if any correlation with uranium
      concentration was apparent. No correlation was found. The results are interpreted
      in relation to the current WHO guideline and those of other countries with a view
      to determining which areas would be affected if a maximum value were to be
      adopted and which areas require further investigation. Uranium content varied
      considerably, from below the limit of detection to almost 100 MUg L(-1). Of the
      5548 data samples, 98% are below the 2004 WHO provisional guideline value of 15
      MUg L(-1) and 99.7% below the revised (2011) value of 30 MUg L(-1).

PMID- 22154003
TI  - Assessment of molluscicidal activity of essential oils from five Azorean plants
      against Radix peregra (Muller, 1774).
AB  - The molluscicidal activity of essential oils from two endemic (Juniperus
      brevifolia; Laurus azorica) and three introduced (Hedychium gardnerianum;
      Pittosporum undulatum; Psidium cattleianum) Azorean plants against the snail
      Radix peregra was studied under laboratory conditions. Essential oils from leaves
      of H. gardnerianum, L. azorica and J.brevifolia presented promising molluscicidal
      activity on both adults and juveniles stages of R. peregra. The molluscicidal
      activity of these essential oils was found to be both time and concentration
      dependent. Lethal concentrations (LC(50)) varied between 15.4 (L. azorica) and
      44.6 ppm (H. gardnerianum) for juveniles and from 45.3 (H. gardnerianum) to 54.6
      ppm (J. brevifolia) for R. peregra adults. Ovicidal effect, calculated as
      percentage of egg hatching, at 100 ppm concentration, was observed in essential
      oils from P. undulatum flowers (4.2% of hatching) and leaves of H. gardnerianum
      (4.9%), L. azorica (7.4%) and J. brevifolia (17.7%). The present study is the
      first attempt to assess the molluscicidal potential of some Azorean plants
      essential oils against a Lymnaeidae snail. In fact, the H. gardnerianum, L.
      azorica and J. brevifolia can offer natural alternative tools for the control of
      R. peregra population, but more research is needed in order to determine the mode
      of action of these oils and determine the side effects on the ecosystem where
      this freshwater snail occurs.

PMID- 22154004
TI  - Partial dissolution of ACQ-treated wood in lithium chloride/N-methyl-2
      pyrrolidinone: separation of copper from potential lignocellulosic feedstocks.
AB  - A cellulose solvent system based on lithium chloride (LiCl) in N-methyl-2
      pyrrolidinone (NMP) was used to assess the merits of partial dissolutions of
      coarsely ground wood samples. Alkaline Copper Quaternary (ACQ)-treated pine wood
      was of particular interest for treatment given the potential to generate a copper
      rich stream apart from solid and/or liquid lignocellulosic feedstocks. Treatment
      with NMP alone gave yields of soluble materials that were higher than typical
      extractives contents thereby suggesting a limited degree of wood dissolution.
      Inclusion of LiCl, which disrupts hydrogen bonding, gave lower wood residue
      recoveries (i.e., higher dissolution) with higher LiCl concentration. Lower wood
      residue recoveries coincided with lower Klason lignin and hemicellulose-derived
      sugar contents in the wood residues. After treatment with 8% LiCl in NMP,
      subsequent filtration afforded 34% of the ACQ-treated sapwood as a wood residue
      retaining only 2% of the original copper. Pouring the filtrate over an excess of
      water resulted in the recovery of 30% of the solids and 50% of the copper
      together as a copper-enriched lignocellulosic precipitate. Results demonstrate a
      solvent system showing potential as a means to separate heavy metals from
      preservative-treated wood and to recover lignocellulosic feedstocks that may be
      suitable for use in a biorefinery.

PMID- 22154005
TI  - Coat colour and sex identification in horses from Iron Age Sweden.
AB  - Domestication of animals and plants marked a turning point in human prehistory.
      To date archaeology, archaeozoology and genetics have shed light on when and
      where all of our major livestock species were domesticated. Phenotypic changes
      associated with domestication have occurred in all farm animals. Coat colour is
      one of the traits that have been subjected to the strongest human selection
      throughout history. Here we use genotyping of coat colour SNPs in horses to
      investigate whether there were any regional differences or preferences for
      specific colours associated with specific cultural traditions in Iron Age Sweden.
      We do this by identifying the sex and coat colour of horses sacrificed at
      Skedemosse, Oland (Sweden) during the Iron Age, as well as in horses from two
      sites in Uppland, Ultuna and Valsgarde (dated to late Iron Age). We show that
      bay, black and chestnut colours were all common and two horses with tobiano
      spotting were found. We also show how the combination of sex identification with
      genotyping of just a few SNPs underlying the basic coat colours can be used to
      identify the minimum number of individuals at a site on a higher level than
      morphological methods alone. Although separated by 500 km and from significantly
      different archaeological contexts the horses at Skedemosse and Ultuna are quite
      homogenous when it comes to coat colour phenotypes, indicating that there were no
      clear geographical variation in coat colouration in Sweden during the late Iron
      Age and early Viking Age.

PMID- 22154006
TI  - Distinct polyfunctional CD4+ T cell responses to BCG, ESAT-6 and CFP-10 in
      tuberculous pleurisy.
AB  - Tuberculous pleurisy (TBP) is a frequent extrapulmonary manifestation
      characterized by the accumulation of inflammatory cells that can sometimes be
      spontaneously self-cured. To achieve a greater insight into T cells at a local
      site, we systematically characterized and compared the numbers of antigen
      specific T cells responding to BCG- or MTB-specific antigens. Our results showed
      that significantly higher levels of Th1 cytokines were produced by pleural fluid
      cells (PFCs) than PBMCs following stimulation with BCG or peptides from
      Mycobacterium tuberculosis (MTB)-specific antigens, ESAT-6 and CFP-10. The
      proportions of Th1 cells producing IL-2 alone or IL-2 and TNF-alpha were higher
      than those producing IFN-gamma alone, following stimulation with ESAT-6 or CFP-10
      peptides. The cells responding to BCG, ESAT-6 and CFP-10 displayed a CD45RA(
      )CCR7(-)CD62L(-)CD27(-) effector/effector memory phenotype. The percentages and
      median fluorescence intensity (MFI) of polyfunctional CD4(+) T cells were
      significantly higher following stimulation with peptides from ESAT-6 or CFP-10
      than BCG. Our results demonstrated that significantly higher levels of
      polyfunctional CD4(+) T cells for the epitopes of ESAT-6 or CFP-10 in PFCs may
      play an important role in the local control of tuberculosis (TB) infection.

PMID- 22154007
TI  - A defect in the synthesis of Interferon-gamma by the T cells of Complement-C5
      deficient mice leads to enhanced susceptibility for tuberculosis.
AB  - Interferon-gamma (IFNgamma) plays a major role during host defense against
      Mycobacterium tuberculosis (Mtb). T cells produce IFNgamma in response to IL-12
      and IL-18 secreted from Mtb infected macrophages. IFNgamma in turn, induces
      nitric oxide secretion in macrophages that kills Mtb. IFNgamma knockout mice are
      thus hyper-susceptible to tuberculosis. We reported earlier that Complement-C5
      deficient (C5(-/-)) congenic mice are more susceptible to tuberculosis and showed
      reduced IL-12 synthesis in their macrophages. Using C5(-/-) congenic mice that
      carry a deletion in the C5 gene and the wild type C5(+/+) mice, we demonstrate
      here that, the C5(-/-) derived CD3(+) T cells, have an additional defect in the
      synthesis of IFNgamma. C5(-/-) T cells produced lower levels of IFNgamma upon
      stimulation by antigen presenting cells (APCs) infected with Mtb or when
      stimulated directly with a combination of IL-12 and IL-18. The latter was in part
      due to a reduced phosphorylation of STAT4 following IL-12/IL-18 stimulation.
      Addition of C5a peptide to IL-12/IL-18 partially restored STAT4 phosphorylation
      and IFNgamma synthesis in C5(-/-) T cells indicating that IL-12/IL-18 mediated
      signaling within CD3(+) T cells involves C5a peptide. Finally, C5(-/-) T cells
      derived from M. bovis BCG or Mtb infected mice showed a reduced expression of T
      bet (T-box expressed in T cells) transcription factor, which correlated well with
      a reduced T cell secretion of IFNgamma. Since T-bet mediated IFNgamma synthesis
      facilitates Th1 expansion, C5(-/-) mouse derived T cells appear to have an
      intrinsic defect in the production of IFNgamma, which is related to C5 deficiency
      and this may explain their increased susceptibility to infection with Mtb and
      BCG.

PMID- 22154008
TI  - Microbial diversity and composition of the sediment in the drinking water
      reservoir Saidenbach (Saxonia, Germany).
AB  - Sediments contain a huge number and diversity of microorganisms that are
      important for the flux of material and are pivotal to all major biogeochemical
      cycles. Sediments of reservoirs are affected by a wide spectrum of allochthous
      and autochthonous influences providing versatile environments along the flow of
      water within the reservoir. Here we report on the microbial diversity in
      sediments of the mesotrophic drinking water reservoir Saidenbach, Germany,
      featuring a pronounced longitudinal gradient in sediment composition in the
      reservoir system. Three sampling sites were selected along the gradient, and the
      microbial communities in two sediment depths were characterized using catalysed
      reporter deposition fluorescence in situ hybridization (CARD-FISH) and a bar
      coded pyrosequencing approach. Multivariate statistic was used to reveal
      relationships between sequence diversity and the environmental conditions. The
      microbial communities were tremendously diverse with a Shannon index of diversity
      (H') ranging from 6.7 to 7.1. 18,986 sequences could be classified into 37 phyla
      including candidate divisions, but the full extent of genetic diversity was not
      captured. While CARD-FISH gave an overview about the community composition, more
      detailed information was gained by pyrosequencing. Bacteria were more abundant
      than Archaea. The dominating phylum in all samples was Proteobacteria, especially
      Betaproteobacteria and Deltaproteobacteria. Furthermore, sequences of
      Bacteroidetes, Verrucomicrobia, Acidobacteria, Chlorobi, Nitrospira,
      Spirochaetes, Gammaproteobacteria, Alphaproteobacteria, Chloroflexi, and
      Gemmatimonadetes were found. The site ammonium concentration, water content and
      organic matter content revealed to be strongest environmental predictors
      explaining the observed significant differences in the community composition
      between sampling sites.

PMID- 22154009
TI  - The effect of VEGF-immobilized nickel-free high-nitrogen stainless steel on
      viability and proliferation of vascular endothelial cells.
AB  - Using ester bonds, vascular endothelial growth factor-A (VEGF-A) was immobilized
      on the surface of a novel biometal, nickel-free high-nitrogen stainless steel
      (HNS). The biological activity of immobilized VEGF-A was investigated after the
      culture of human umbilical vein endothelial cells (HUVECs) on the substrate.
      Immobilization of VEGF-A onto the HNS surface was performed using trisuccinimidyl
      citrate (TSC) as a linker. Firstly, UV irradiation was employed to amplify
      hydroxyl groups on the HNS surface. Next, the HNS was dipped into TSC/dimethyl
      sulfoxide solution at room temperature. From the results of water contact angle
      measurement and X-ray photoelectron spectroscopy (XPS) analysis, TSC was found to
      be immobilized on the HNS surface via ester bonds. Quantitative analysis
      demonstrated that immobilized VEGF-A remained even after immersion in culture
      medium for 7 days; however, it was gradually deimmobilized by hydrolysis of the
      ester bonds at the TSC-metal interface. As a result, VEGF-A-immobilized HNS
      significantly contributed to the stimulation of HUVEC growth for the initial
      stage of culture, even though the gradual reduction in growth stimulation of
      HUVECs occurred by the sequential deimmobilization of VEGF-A, which was caused by
      the hydrolysis of the ester groups. Therefore, VEGF-A-immobilized HNS could be
      applied as a basic material for coronary stents.

PMID- 22154010
TI  - Green preparation of antibiotic nanoparticle complex as potential anti-biofilm
      therapeutics via self-assembly amphiphile-polyelectrolyte complexation with
      dextran sulfate.
AB  - Nanoscale antibiotic delivery has emerged as a promising therapeutic means to
      treat lung biofilm infection owed to its sputum penetrating ability. Due to the
      high antibiotic dosage requirement in anti-biofilm therapy, the most suitable
      formulation for this purpose is the antibiotic nanoparticles themselves, instead
      of the more extensively studied antibiotic-loaded nano-carriers, which often
      exhibit low drug loading. The present work details the preparation and
      characterization of antibiotic nanoparticle complex (or nanoplex) by self
      assembly amphiphile-polyelectrolyte complexation process. Ofloxacin (OFX) and
      levofloxacin (LEV) are used as the antibiotics with dextran sulfate (DXT) as the
      polyelectrolyte. The nanoplex possesses high drug loading (up to 80%) and
      size<400nm ideal for sputum penetration. Unlike existing methods to prepare drug
      nanoparticles, the present method is fast, energy-minimal, solvent-free, and
      highly efficient as manifested in nearly 100% of drug is transformed into
      nanoplex. The effects of drug-to-polyelectrolyte charge ratio, pH, drug, and salt
      concentrations on the nanoplex characteristics (i.e. size, stability, drug
      loading) are investigated from which the optimal preparation conditions have been
      identified. Higher complexation efficiency and stronger agglomeration tendency
      are observed for LEV nanoplex owed to its higher hydrophobicity. The antibiotics
      are completely released from the nanoplex in aqueous salt solution within 3h and
      their antimicrobial activity is preserved upon complexation. The nanoplex is
      readily transformed into amorphous dry powders that remain stable after one-month
      storage owed to the high glass transition temperature. The antibiotic nanoplexes
      are highly charged enabling their subsequent functionalization for targeted
      delivery and controlled drug release purposes.

PMID- 22154011
TI  - Entrapment of epirubicin in poly(butyl cyanoacrylate) colloidal nanospheres by
      nanoprecipitation: formulation development and in vitro studies on cancer cell
      lines.
AB  - This report describes the preparation of poly(butyl cyanoacrylate) nanospheres
      loaded with epirubicin by nanoprecipitation, their characterization and in vitro
      evaluation of the drug uptake and cytotoxicity on cancer cell lines. The
      epirubicin-loaded nanospheres were prepared by nanoprecipitation using
      presynthesized polymer and dextran 40 as a colloidal stabilizer at different pH
      and initial drug concentrations. The nanospheres were characterized for particle
      morphology, size distribution, zeta-potential and drug loading. Epirubicin-loaded
      particles with diameters around 350 nm were obtained. Drug loading depended on
      the pH and epirubicin concentration. Epirubicin was more cytotoxic when loaded in
      nanospheres. Drug release was studied by dialysis method. Cytotoxicity and drug
      uptake experiments were performed on HeLa and A549 cell lines. It was found that
      addition of polysorbate 80 could increase cytotoxicity. The cytotoxicity was
      found to correlate with the drug uptake by cells. The findings reported here
      demonstrate that epirubicin-loaded nanospheres of poly(butyl cyanoacrylate) can
      be successfully prepared by the nanoprecipitation approach as alternative to the
      well-known polymerization-based methods. It is found that the epirubicin-loaded
      nanospheres are more cytotoxic than the free drug to human carcinoma cell lines
      in vitro. The higher cytotoxicity of the obtained epirubicin formulations,
      compared with the free drug, is due to enhanced cellular internalization of
      epirubicin.

PMID- 22154012
TI  - Final incision size after implantation of a hydrophobic acrylic aspheric
      intraocular lens: new motorized injector versus standard manual injector.
AB  - PURPOSE: To assess the impact on incision size of IOL implantation using a new
      motorized intraocular lens (IOL) injector versus a standard manual injector.
      SETTING: Cataract Treatment Centre, Sunderland Eye Infirmary, Sunderland, United
      Kingdom. DESIGN: Comparative case series. METHODS: All patients received an
      Acrysof SN60WF IOL implanted using a D cartridge and an Autosert motorized
      injector at fast speed, an Autosert motorized injector at slow speed, or a manual
      Monarch injector. Each group had a range of preimplantation incision sizes (1.9
      mm, 2.0 mm, 2.1 mm, 2.2 mm, 2.3 mm). Incision gauges were used to measure the
      incision width before and immediately after IOL implantation. RESULTS: The study
      recruited 256 patients. All incisions that were 1.8 mm at the commencement of
      surgery increased in size by the end of irrigation/aspiration. The motorized
      injector used with a fast speed (4.4 mm/sec) caused significantly less incision
      enlargement than the manual injector for all preimplantation incision sizes
      tested (P<.02). For 4 of the 5 preimplantation incision size subgroups, the
      motorized injector used at slow speed (1.5 mm/sec) produced less incision stretch
      than the manual injector, although the difference did not reach statistical
      significance. CONCLUSION: The motorized injector was easy to use, and its use
      with an injection speed of 4.4 mm/sec caused significantly less incision
      enlargement than the manual injector during IOL implantation.

PMID- 22154013
TI  - Takotsubo cardiomyopathy related to compound electrolyte aberration and anemia in
      Crohn's disease.

PMID- 22154014
TI  - Dobutamine stress MRI in repaired tetralogy of Fallot with chronic pulmonary
      regurgitation: a comparison with healthy volunteers.
AB  - BACKGROUND: To compare the ventricular response to dobutamine stress between
      adult patients with chronic pulmonary regurgitation (PR) after repair of
      tetralogy of Fallot (r-TOF) and healthy volunteers using a staged dobutamine
      stress MR (DS-MR) protocol. METHODS: Eighteen r-TOF patients (median age 31.9
      years, range 16.2-60.1) with severe PR and 10 healthy controls (median age 40.6
      years, range 23.9-51.8) completed staged DS-MR (baseline, 10 and 20 MUg/kg/min)
      with ventricular volumetry and pulmonary flow quantification. Comparative
      analysis involved 3-way ANOVA, t-test, regression analysis, and coefficient of
      variance. RESULTS: All controls had significant increase of ejection fraction
      (EF) at each stress level for both ventricles (normal contractile reserve, all
      p<0.05). In r-TOF patients (RV-EDV 126 +/- 27 ml/m(2), RV-EF 55 +/- 7%, LV-EF 58
      +/- 6%, PR-fraction 43 +/- 15%), low-dose DS-MR at 10 MUg/kg/min demonstrated
      normal biventricular contractile reserve as seen in volunteers. On increase from
      10 to 20 MUg/kg/min a subgroup showed worsening ejection fraction (n=8, p<0.05),
      mainly due to lack of reduction or even increase of RV-ESV, while the remainder
      responded with further reduction of RV-ESV and RV-EDV (n=10, p<0.05) and a non
      significant trend to increased EF. This different response could not be predicted
      at baseline. CONCLUSIONS: In r-TOF patients with chronic PR, DS-MR at 10
      MUg/kg/min showed normal biventricular systolic response compared with controls.
      Increase to 20 MUg/kg/min provoked abnormal RV-ESV response in some r-TOF
      patients, suggesting presence of ventricular systolic dysfunction not evident at
      rest.

PMID- 22154015
TI  - Development of a fast ELISA for quantifying polio D-antigen in in-process
      samples.
AB  - A fast ELISA was developed and qualified for analysis of polio D-antigen. The
      original 20 h-protocol was optimized by minimizing the total incubation time to 1
      h, and by replacing the signal reagent 3,3',5,5'-tetramethylbenzidine by a
      chemiluminogenic signal reagent with a theoretical low intrinsic background and
      high dynamic range.

PMID- 22154016
TI  - Multiple cranial nerve dysfunction caused by neurosarcoidosis.
AB  - Neurosarcoidosis is a rare identity and occurs in only 5% to 15% of patients with
      sarcoidosis. It can manifest in many different ways, and therefore, diagnosis may
      be complicated. We report a case presented in a very unusual manner with
      involvement of 3 cranial nerves; anosmia (NI), facial palsy (NVII), and hearing
      loss (NVIII). When cranial nerve dysfunction occurs, it is very important to take
      neurosarcoidosis into consideration.

PMID- 22154017
TI  - Work environment discomfort and injury: an ergonomic survey study of the American
      Society of Pediatric Otolaryngology members.
AB  - BACKGROUND: Workplace-related musculoskeletal pain has been studied in various
      occupations, but it is rarely reported in the surgical literature. OBJECTIVE: The
      aim of this study was to examine work-related discomfort and injury among
      pediatric otolaryngologists and to assess their knowledge of workplace ergonomic
      principles. METHODS: We surveyed current North American members of the American
      Society of Pediatric Otolaryngology. Our main outcomes were whether the physician
      had ever experienced discomfort or physical symptoms that they attributed to
      their surgical practice. RESULTS: Response rate of 43.7% was attained, and 62.0%
      of respondents reported experiencing pain or discomfort that they attributed to
      their surgical practice. Women were significantly more likely to report
      experiencing pain or discomfort that they associated with their surgical practice
      (P = .033). There were no significant differences found among length of time in
      practice, academic vs community setting, or number of surgeries completed by the
      surgeon. Some of the surgeons (31.0%) were aware of ergonomic principles, and of
      those who were aware, 83.9% had implemented ergonomic principles into their
      surgical practice. CONCLUSION: Almost two thirds of surgeons who responded to the
      survey reported experiencing pain or discomfort that they attributed to their
      surgical practice. Only a minority of respondents were aware of ergonomic
      principles. These findings may confirm that most physicians believe that their
      physical health is affected by their operative environment. Increased knowledge
      of surgical ergonomics may lead to strategies that improve workplace health and
      safety.

PMID- 22154019
TI  - An objective comparison of leakage between commonly used earplugs.
AB  - OBJECTIVE: We sought to determine the efficacy of commonly used earplugs using an
      anatomically correct ear model. METHODS: The total volume and rate of water that
      leaked past the earplug and subsequent defect in the tympanic membrane over
      separately measured 30, 60, 120, and 180-second intervals were recorded.
      Scenarios tested included a control with no earplug, custom molded earplug
      (Precision Laboratories, Orlando, FL), Mack's plug (Warren, MI), Doc's plug
      (Santa Cruz, CA), and cotton balls coated with petroleum jelly. RESULTS: All
      plugs tested resulted in less leakage at all time points when compared with no
      plug (P < .05). At 30 seconds, the custom molded, Mack's and Doc's plugs all
      showed significantly less leakage when compared with the cotton ball coated with
      petroleum jelly (P < .05). At 60, 120, and 180 seconds, Mack's, Doc's, and the
      cotton plugs all showed significantly less leakage compared with the customized
      plug (P < .05). At 120 and 180 seconds, Mack's plugs had significant less leakage
      than the cotton plug (P < .05). Among the types of plugs, the molded variety
      (Mack's) showed the least volume and lowest leakage rate (f(4,45) = 94 [P <
      .001]). In addition, Doc's and cotton balls coated with petroleum jelly were more
      effective than the customized earplugs. CONCLUSIONS: If the clinician feels that
      middle ear and external canal water exposure should be minimized, then use of
      earplugs, particularly the moldable variety, merits further consideration.

PMID- 22154018
TI  - Imaging techniques in parathyroid surgery for primary hyperparathyroidism.
AB  - As more patients present with the incidental diagnosis of primary
      hyperparathyroidism due to biochemical screening, treatment guidelines have been
      developed for the treatment of hyperparathyroidism. Management of primary
      hyperparathyroidism has evolved in recent years, with considerable interest in
      minimally invasive approaches. Successful localization of the diseased gland(s)
      by nuclear imaging and anatomical studies, along with rapid intraoperative
      parathyroid hormone assay, has allowed for focused and minimally invasive
      surgical approaches. Patients in whom the localization studies have identified
      single-gland adenoma or unilateral disease are candidates for such focused
      approaches instead of the traditional approach of bilateral exploration. These
      imaging techniques have also been critical in the successful management of
      patients with persistent or recurrent disease.

PMID- 22154020
TI  - Superior laryngeal nerve syndrome and the evaluation of anterior neck pain.

PMID- 22154021
TI  - Sex chromosome aneuploidies among men with systemic lupus erythematosus.
AB  - About 90% of patients with systemic lupus erythematosus (SLE) are female. We
      hypothesize that the number of X chromosomes, not sex, is a determinate of risk
      of SLE. Number of X chromosomes was determined by single nucleotide typing and
      then confirmed by karyotype or fluorescent in situ hybridization in a large group
      of men with SLE. Presence of an sry gene was assessed by RT-PCR. We calculated
      96% confidence intervals using the Adjusted Wald method, and used Bayes' theorem
      to estimate the prevalence of SLE among 47,XXY and 46,XX men. Among 316 men with
      SLE, 7 had 47,XXY and 1 had 46,XX. The rate of Klinefelter's syndrome (47,XXY)
      was statistically different from that found in control men and from the known
      prevalence in the population. The 46,XX man had an sry gene, which encodes the
      testes determining factor, on an X chromosome as a result of an abnormal
      crossover during meiosis. In the case of 46,XX, 1 of 316 was statistically
      different from the known population prevalence of 1 in 20,000 live male births. A
      previously reported 46,XX man with SLE had a different molecular mechanism in
      which there were no common gene copy number abnormalities with our patient. Thus,
      men with SLE are enriched for conditions with additional X chromosomes.
      Especially since 46,XX men are generally normal males, except for infertility,
      these data suggest the number of X chromosomes, not phenotypic sex, is
      responsible for the sex-bias of SLE.

PMID- 22154022
TI  - Phase I trial of sodium salicylate in patients with myelodysplastic syndromes and
      acute myelogenous leukemia.
AB  - Sodium salicylate is an inexpensive, readily available anti-inflammatory agent
      which inhibits NF-kappaB in in vitro models. We examined whether it was possible
      to safely achieve and maintain salicylate levels known to inhibit NF-kappaB in
      vitro in 11 patients with MDS or AML taking sodium salicylate. Most patients
      achieved the target blood salicylate level (20-30mg/dL) with acceptable toxicity,
      including reversible grade 1/2 elevations of hepatic transaminases (n=4) and
      ototoxicity (n=4). One patient had grade 3/4 elevations in AST/ALT. This study
      suggests that sodium salicylate may be safely combined with conventional
      chemotherapy regimens which are not associated with significant ototoxicity or
      hepatotoxicity.

PMID- 22154023
TI  - Clinical experience of bendamustine treatment for non-Hodgkin lymphoma and
      chronic lymphocytic leukemia in Spain.
AB  - Bendamustine is a alkylating agent with a purine-like benzamidazole ring
      currently approved in Europe for indolent non-Hodgkin lymphoma (NHL), chronic
      lymphocytic leukemia (CLL) and multiple myeloma. Our aim was to analyze
      retrospectively the efficacy and toxicity of bendamustine in NHL and CLL in Spain
      in the bendamustine Compassionate Use Program. Patients with relapsed/refractory
      NHL or CLL were eligible. Any regimen containing bendamustine was eligible. 109
      patients were included from 22 institutions. Forty-nine patients had indolent
      NHL, 18 aggressive NHL and 42 CLL, being 44 patients (40%) refractory to previous
      treatment. 63% of patients had adverse events grade 3-4, mainly hematological.
      Overall response rate (ORR) was 66%, complete responses 30%. ORR observed in
      refractory patients was 45%. The median progression-free survival (PFS) was 13
      months. Outcome was influenced by histology, number of previous treatments,
      resistance to previous chemotherapy and type of response achieved with
      bendamustine. Alone or in combination, bendamustine shows a meaningful clinical
      antitumor activity in patients with relapsed or refractory NHL or CLL, with an
      acceptable toxicity profile.

PMID- 22154024
TI  - Continuous improvement versus innovation: the case for sipuleucel-T.

PMID- 22154025
TI  - Program needs and change orientation: implications for counselor turnover.
AB  - Although evidence suggests that turnover rates are higher in high-stress/high
      needs work environments, it is unclear whether agencies' attempts at improving
      practices influence individuals' decisions to stay at or leave a job. The purpose
      of this study was to examine whether program needs and change orientation
      influence individual decisions to quit. A sample of 206 counselors from 25
      outpatient substance abuse treatment programs completed the Survey of
      Organizational Functioning, rating the organization on program needs, leadership,
      and change. They also rated themselves on stress, burnout, and job satisfaction.
      Multilevel modeling indicated a significant interaction between program needs and
      change orientation, even after controlling for stress, burnout, job satisfaction,
      tenure, and selected program characteristics. When perceptions of program needs
      were high, counselors were more likely to stay if they felt that the organization
      was making progress toward change. These findings suggest that an orientation
      toward change can counteract negative effects of perceived need within the
      workplace.

PMID- 22154026
TI  - Tobacco use and psychiatric comorbidity among adolescents in substance abuse
      treatment.
AB  - Adolescents in substance abuse treatment have approximately four times higher
      rates of tobacco use compared with adolescents in the general population, yet
      many substance abuse treatment programs do not provide tobacco cessation
      interventions. This study examined change in tobacco use among 151 adolescents in
      state-funded substance abuse treatment from intake to 12-month follow-up in
      relation to psychiatric comorbidity and substance use. Most adolescents (67.5%)
      used tobacco at intake and follow-up. Having a diagnosis of a mood, anxiety, or
      behavioral disorder was significantly associated with change in tobacco use.
      Individuals with a psychiatric disorder were less likely to be nonusers of
      tobacco than to be individuals who continued tobacco use (adjusted odds ratio
      [OR] = 0.153, 95% confidence interval [CI] = 0.040-0.587, p < .01), and they were
      less likely to have initiated tobacco use at follow-up than individuals who
      continued tobacco use (adjusted OR = 0.320, 95% CI = 0.105-0.970, p < .05).
      Contrary to the hypothesis, alcohol use and drug use during the 12-month follow
      up was not significantly related to change in tobacco use. Adolescents in
      substance abuse treatment with comorbid psychiatric disorders may be particularly
      vulnerable to continuing tobacco use.

PMID- 22154027
TI  - Examination of the latent factor structure of the Alcohol Use Disorders
      Identification Test in two independent trauma patient groups using confirmatory
      factor analysis.
AB  - Recent research on the factor structure of the Alcohol Use Disorders
      Identification Test (AUDIT) provides support for two underlying factors:
      consumption and consequences. The current study sought to extend these findings
      to two independent and diverse trauma populations: traumatic injury patients and
      military veterans treated for posttraumatic stress disorder. The 2- and 3-factor
      solutions provided the best fit to the data, but there was a very high
      correlation between the second and third factors of the 3-factor solution.
      Parsimony suggests that the 2-factor solution is the preferred model. The 2
      factor model has implications for alcohol screening using the AUDIT and supports
      the goal of screening to identify those with hazardous drinking and alcohol use
      disorders. An algorithm is proposed to inform alcohol screening protocols in a
      range of health settings for trauma-exposed patient groups.

PMID- 22154028
TI  - Organizational consequences of staff turnover in outpatient substance abuse
      treatment programs.
AB  - The purpose of this study was to examine the impact of staff turnover on
      perceptions of organizational demands and support among staff who remained
      employed in substance abuse treatment programs. The sample consisted of 353
      clinical staff from 63 outpatient agencies. Two scales from the Survey of
      Organizational Functioning measured work environment demands (stress and
      inadequate staffing), and 3 measured supportive work relationships
      (communication, cohesion, and peer collaboration). Results from a series of
      multilevel models documented that counselors working in programs that had
      previously experienced high staff turnover perceived higher demands and lower
      support within their organization, even after controlling for other potentially
      burdensome factors such as budget, census, and individual measures of workload.
      Two individual-level variables, caseload and tenure, were important determinants
      of work environment demands but were not related to supportive work
      relationships. Findings suggest that staff turnover increases workplace demands,
      decreases perceptions of support, and underscores the need to reduce stress and
      minimize subsequent turnover among clinical staff.

PMID- 22154029
TI  - The impact of organizational stress and burnout on client engagement.
AB  - This article explores the impact of organizational attributes on client
      engagement within substance abuse treatment. Previous research has identified
      organizational features, including small size, accreditation, and workplace
      practices, that impact client engagement (K. M. Broome, P. M. Flynn, D. K.
      Knight, & D. D. Simpson, 2007). This study sought to explore how aspects of the
      work environment impact client engagement. The sample included 89 programs
      located in 9 states across the United States. Work environment measures included
      counselor perceptions of stress, burnout, and work satisfaction at each program,
      whereas engagement measures included client ratings of participation, counseling
      rapport, and treatment satisfaction. Using multiple regression, tests of
      moderation and mediation revealed that staff stress negatively predicted client
      participation in treatment. Burnout was related to stress but was not related to
      participation. Two additional organizational measures--workload and influence-
      moderated the positive relationship between staff stress and burnout.
      Implications for drug treatment programs are discussed.

PMID- 22154030
TI  - Innovation adoption as facilitated by a change-oriented workplace.
AB  - One of the unique contributions of this study is a glimpse into the process by
      which counselors decide to try new innovations in their clinical work. Data were
      collected from 421 counseling staff from 71 outpatient treatment programs in 4
      U.S. regions. Using hierarchical linear modeling, results reveal that the
      propensity to adopt workshop-based interventions is facilitated by two important
      mechanisms: (a) an innovative organization with creative leadership and (b)
      change-oriented staff attributes (i.e., seeking professional growth, efficacy,
      adaptability, and influence on others). Innovative leaders and a climate
      receptive to change also bolster the development of these change-oriented
      attributes. One implication of these findings is the cascading effect of leaders'
      support of innovative thinking and action resulting in employees strengthening
      their own adaptive skills and carrying this innovative thinking into individual
      adoption.

PMID- 22154031
TI  - Resources and training in outpatient substance abuse treatment facilities.
AB  - The exposure to new clinical interventions through formalized training and the
      utilization of strategies learned through training are two critical components of
      the program change process. This study considers the combined influence of actual
      program fiscal resources and counselors' perceptions of workplace resources on
      two mechanisms of training: exposure and utilization. Data were collected from
      323 counselors nested within 59 programs located in nine states. Multilevel
      analysis revealed that training exposure and training utilization represent two
      distinct constructs that are important at different stages in the Program Change
      Model. Training exposure is associated primarily with physical and financial
      resources, whereas utilization is associated with professional community and job
      burnout. These results suggest that financial resources are important in initial
      exposure to new interventions but that successful utilization of new techniques
      depends in part on the degree of burnout and collaboration experienced by
      counselors.

PMID- 22154032
TI  - Drug treatment program ownership, Medicaid acceptance, and service provision.
AB  - The Institute of Medicine noted that effective substance abuse treatment (SAT)
      programs integrate individual therapeutic approaches with transitional/ancillary
      services. In addition, research suggests that type of ownership impacts SAT
      services offered and that Medicaid plays a key role in SAT access. Data from the
      National Survey of Substance Abuse Treatment Services for the years 2000 and 2002
      2006 were used to examine relationships among SAT program Medicaid acceptance,
      program ownership, and transitional/ancillary service accessibility. Multivariate
      logistic regression models controlling for state- and program-level contextual
      factors were used to analyze the data. Nonprofit SAT programs were significantly
      more likely to offer transitional/ancillary services than for-profit programs.
      However, programs that accepted Medicaid, regardless of ownership, were
      significantly more likely to offer most transitional/ancillary services. The data
      suggest that Medicaid may play a significant role in offering key
      transitional/ancillary services related to successful treatment outcome,
      regardless of program ownership type.

PMID- 22154033
TI  - Treatment program operations and costs.
AB  - This study investigates how average costs for an episode of care in outpatient
      drug-free (ODF) treatment relate to clinical intensity (length of stay and weekly
      counseling hours) and program structure (e.g., size, staffing), controlling for
      prices paid and selected clientele measures. Based on cost assessments from a
      naturalistic sample of 67 programs located across the United States (using the
      Treatment Cost Analysis Tool), robust regression techniques showed that programs
      having 10% longer treatment stays had episode costs 7% higher; those having 10%
      more weekly counseling hours per client had 4% higher episode costs. Other
      important factors included wages, amount of counselors' time conducting sessions,
      and serving more clients referred from the criminal justice system. The study
      provides valuable information on treatment program features that relate to costs.
      Most importantly, cost differences associated with longer stays or more intensive
      counseling protocols appear modest and may be justified by improved client
      outcomes.

PMID- 22154034
TI  - A gender-specific approach to improving substance abuse treatment for women: The
      Healthy Steps to Freedom program.
AB  - Given that women increasingly report using drugs to lose weight, substance abuse
      treatment programs must include body image, weight, eating pathology, and health
      knowledge as core intervention targets. This study tested the efficacy of a
      supplemental health and body image curriculum designed for women in substance
      abuse treatment who report weight concerns called Healthy Steps to Freedom (HSF).
      Data from 124 adult women recruited from substance abuse treatment facilities in
      southern Nevada completed measures of drug use, body dissatisfaction, eating
      pathology, thin-ideal internalization, and health knowledge/behaviors before and
      after participation in the 12-week HSF program. Results revealed that thin-ideal
      internalization, body dissatisfaction, and eating disorder symptoms significantly
      decreased after HSF program participation, whereas health-related behaviors
      (e.g., increased healthy food consumption) and knowledge (e.g., understanding of
      basic nutrition, exercise) increased. These results suggest that the inclusion of
      the HSF program in substance abuse treatment improves weight-related issues in
      substance-abusing women.

PMID- 22154035
TI  - Factors associated with methadone treatment among injection drug users in
      Bangkok, Thailand.
AB  - Little is known about the characteristics of injection drug users (IDU) who take
      methadone treatment in Thailand. We examined prevalence and correlates of
      methadone treatment among a community-recruited sample of IDU in Bangkok,
      Thailand. Among 273 participants, 143 (52.4%) reported accessing methadone
      treatment within the previous 6 months. Older age (adjusted odds ratio [AOR] =
      1.90, 95% confidence interval [CI] = 1.10-3.30) and more than weekly midazolam
      injection (AOR = 1.85, 95% CI = 1.04-3.29) were positively associated, whereas
      alcohol use (AOR = 0.34, 95% CI = 0.18-0.63) and noninjection methamphetamine use
      (AOR = 0.49, 95% CI = 0.29-0.85) were negatively associated with methadone
      treatment. In subanalyses, 98.6% of IDU on methadone continued to inject drugs,
      and the most common reason for stopping methadone was becoming incarcerated
      (49%). Evidence-based addiction treatment in the form of methadone maintenance
      therapy, with attention paid to concomitant midazolam injection in this setting,
      should be implemented.

PMID- 22154036
TI  - Does the alcohol use disorders identification test-consumption identify the same
      patient population as the full 10-item alcohol use disorders identification test?
AB  - The aim of this study was to evaluate whether a computer-based 3-item version
      (Alcohol Use Disorders Identification Test-Consumption [AUDIT-C]) of the Alcohol
      Use Disorders Identification Test (AUDIT) identifies alcohol use disorder (AUD)
      in the same patients as the full 10-item version in 809 women and 747 men in an
      anesthesiology preoperative assessment clinic. According to cutoffs used ( AUDIT:
      5-8 points, AUDIT-C: 4-6 points), rate of disagreement (AUDIT-positive and AUDIT
      C-negative or vice versa) ranged between 4% and 31% (men) and between 4% and 19%
      (women). In male patients, 15% were positive for both the AUDIT (>=8 points) and
      the AUDIT-C (>=6 points), 7% were positive for AUDIT-C only, and 4% were positive
      for AUDIT only. In female patients, using cutoffs of 5 more points (AUDIT) and 4
      or more points (AUDIT-C), 16% were positive for both versions, 9% were positive
      for AUDIT-C only, and 2% were positive for AUDIT only. The AUDIT and AUDIT-C seem
      to identify AUD in differing patients.

PMID- 22154037
TI  - Community-based group intervention for tobacco cessation in rural Tamil Nadu,
      India: a cluster randomized trial.
AB  - The objective of this study was to determine the efficacy of community-based
      group intervention for tobacco cessation. We recruited 400 men (20-40 years)
      currently using any form of tobacco from 20 villages of the Indian State of Tamil
      Nadu and randomized them equally into intervention and control groups. A
      physician offered two sessions of health education 5 weeks apart along with self
      help material on tobacco cessation to the intervention group. The control group
      received only self-help material. The contents of the sessions included tobacco
      related health problems, benefits of quitting, and coping strategies for
      withdrawal symptoms. Follow-up data were available for 92%. Self-reported point
      prevalence abstinence of 12.5% in the intervention group was significantly higher
      than the 6.0% in the control group at 2 months. Community-based group
      intervention has the potential to increase the coverage of tobacco cessation
      services for men in rural Tamil Nadu.

PMID- 22154038
TI  - Community Reinforcement and Family Training: a pilot comparison of group and self
      directed delivery.
AB  - In a randomized clinical pilot study, 40 concerned significant others (CSOs) of
      treatment-refusing alcohol- and drug-using individuals were randomized to either
      Community Reinforcement and Family Training (CRAFT) conducted in a group format
      (Group CRAFT) or a Self-Directed CRAFT condition. Although results indicated no
      significant between-group difference in engaging treatment-refusing substance
      using individuals (referred to as identified patients or IPs) into treatment, the
      engagement rate in Group CRAFT was similar to rates previously reported with
      individual CRAFT. For the intent-to-treat analysis, 60% of Group CRAFT CSOs
      engaged their loved one into treatment, as compared with 40% in Self-Directed
      CRAFT. Of CSOs in the Group condition who received at least one session of group
      therapy, 71% engaged their IP into treatment. CSOs in both conditions reported
      improvements in family cohesion and conflict at the 3- and 6-month follow-up,
      replicating prior CRAFT findings.

PMID- 22154039
TI  - System-level effects of integrating a promising treatment into juvenile drug
      courts.
AB  - This study examined the system-level effects of implementing a promising
      treatment for adolescent substance abuse in juvenile drug courts (JDCs). Six JDCs
      were randomized to receive training in the experimental intervention (contingency
      management-family engagement [CM-FAM]) or to continue their usual services (US).
      Participants were 104 families served by the courts, 51 therapists, and 74 JDC
      stakeholders (e.g., judges, prosecutors, defense attorneys). Assessments included
      repeated measurements of CM-FAM implementation by therapists and therapist and
      stakeholder perceptions of incentive-based interventions and organizational
      characteristics. Results revealed greater use of CM and family engagement
      techniques among CM-FAM relative to US therapists. In addition, therapists and
      stakeholders in the CM-FAM condition reported more favorable attitudes toward the
      use of incentives and greater improvement on several domains of organizational
      functioning relative to US counterparts. Taken together, these findings suggest
      that JDC professionals are amenable to the adoption and implementation of a
      treatment model that holds promise for improving youth outcomes.

PMID- 22154040
TI  - Treatment staff turnover in organizations implementing evidence-based practices:
      turnover rates and their association with client outcomes.
AB  - High staff turnover has been described as a problem for the substance use
      disorder treatment field. This assertion is based primarily on the assumption
      that staff turnover adversely impacts treatment delivery and effectiveness. This
      assumption, however, has not been empirically tested. In this study, we computed
      annualized rates of turnover for treatment staff (N = 249) participating in an
      evidence-based practice implementation initiative and examined the association
      between organizational-level rates of staff turnover and client-level outcomes.
      Annualized rates of staff turnover were 31% for clinicians and 19% for clinical
      supervisors. In addition, multilevel analyses did not reveal the expected
      relationship between staff turnover and poorer client-level outcomes. Rather,
      organizational-level rates of staff turnover were found to have a significant
      positive association with two measures of treatment effectiveness: less
      involvement in illegal activity and lower social risk. Possible explanations for
      these findings are discussed.

PMID- 22154041
TI  - Repetitive cerebrospinal fluid flushing in a preterm newborn with
      posthaemorrhagic hydrocephalus. Technical note and review of literature.

PMID- 22154042
TI  - Occipital seizures manifesting as visual loss with post-ictal Anton's syndrome.

PMID- 22154043
TI  - Thrombotic thrombocytopenic purpura and its look-alikes: a single institution
      experience.
AB  - At presentation, variant or "look-alike" conditions can resemble TTP. We reviewed
      charts of 26 consecutive patients treated for presumed TTP. Of 15 classic TTP
      patients, 11 were tested for ADAMTS13; all showed severe deficiency, and
      inhibitor levels correlated with probability of relapse. The variant TMA group
      consisted of 8 patients who had active clinical disorders which overlapped with
      TTP. Variant TMA patients had higher creatinine and worse prognosis than classic
      TTP patients. "Look-alike" disorders included ITP with intravascular hemolysis
      following administration of WinRhoTM, and human granulocytic anaplasmosis. These
      conditions had not been previously described as TTP look-alikes.

PMID- 22154044
TI  - Acute autologous bone flap infection after cranioplasty for postinjury
      decompressive craniectomy.
AB  - BACKGROUND: Acute bone flap infection is a devastating complication after
      cranioplasty for postinjury decompressive craniectomy. We aim to identify the
      risk factors of autologous bone flap infection. METHODS: We enrolled 151 patients
      undergoing 153 cranioplasties in the 4-year retrospective study. Autologous bones
      stored at -75 degrees C were used in the cranioplasties. Acute bone flap
      infection was defined as the onset of infection <=14 days after cranioplasty. The
      epidemiological data of patients and details of the cranioplasty procedure were
      recorded. RESULTS: Acute bone flap infection was identified in five of the 153
      cranioplasties, accounting for 3.3% of all episodes. Three of the 5 infected
      patients and five of 143 uninfected patients presented with dysfunction of
      subgaleal drainage comparatively, which was significantly different (p=0.001).
      Statistical analysis of the cranioplasty procedures and subsequent results of the
      two patient groups revealed the following significant findings: the duration of
      operation (p=0.03) and the length of hospital stay after cranioplasty (p<0.001).
      CONCLUSIONS: Dysfunction of subgaleal drainage and long operative duration of
      cranioplasty are risk factors of acute autologous bone flap infection. Regarding
      the prolonged hospital stay in complicated patients, better surgical techniques
      should be implemented in order to eliminate the risks of infection.

PMID- 22154045
TI  - Late formation of heterotopic bone following an adductor origin avulsion injury.

PMID- 22154046
TI  - The increasing incidence of paediatric diaphyseal both-bone forearm fractures and
      their internal fixation during the last decade.
AB  - BACKGROUND: The incidence of children's forearm fractures is increasing
      worldwide. This is different from the declining trend observed in the overall
      injury rate, and the reason for the increase is not known. Diaphyseal forearm
      fractures comprise 3-6% of all paediatric fractures, and they offer a challenge
      to their treatment. The purpose of this study was to evaluate the incidence of
      diaphyseal both-bone forearm fractures in children during the last decade in
      Northern Finland. Another objective was to study the background factors,
      treatment, and re-displacement of these fractures. MATERIALS AND METHODS: All 168
      children (<16 years) admitted to our paediatric trauma centre due to diaphyseal
      both-bone forearm fractures during 2000-2009 were included. The type of injury,
      background factors, radiographics, treatments and re-dislocations were reviewed.
      The age-related incidence rates were evaluated. RESULTS: The incidence of
      diaphyseal both-bone forearm fractures increased 4.4-fold (95% CI 2.0-10.8;
      P<0.001) between 2000 (8.2/100000) and 2009 (35.9/100000). The increase in the
      incidence was accelerating (P<0.001) and the overall increase was 338%. The
      incidence of surgical treatment for diaphyseal fractures increased 4.2-fold (95%
      CI 1.9-10.4, P=0.001), which is in relation to increasing number of fractures.
      However, internal fixation increased from 13.3% in 2000-2001 to 52.7% in 2008
      2009 (P=0.015), as an alternative to conservative treatment. The re-displacement
      rate was high (29.9%) amongst the patients with conservative treatment compared
      to those who were invasively operated (1.4%) (P<0.001). The mean age of the
      patients increased by 2.4 years in the study period (P=0.019). Trampoline was the
      most important and still increasing reason for the fractures. At the beginning of
      the study, there were no trampoline-related fracture, but towards the end of the
      study 30-41% of the fractures were caused by a trampoline injury (P=0.004).
      CONCLUSIONS: There was an accelerating increase in the incidence of paediatric
      diaphyseal both-bone forearm fractures during the last decade. Trampoline was the
      most important and still increasing reason for these fractures. The mean age of
      the patients was increasing. Increasing proportion of diaphyseal both-bone
      forearm fractures was treated operatively. Re-displacement was unusual amongst
      operated cases.

PMID- 22154047
TI  - Intramedullary nailing versus submuscular plating in adolescent femoral fracture.
AB  - BACKGROUND: Femoral fractures in adolescents usually need operative treatment,
      but the optimal method is unclear. The purpose of this study is to compare
      intramedullary nailing (IN) and submuscular plating (SP) in adolescent femoral
      fractures. MATERIALS AND METHODS: We performed the prospective, comparison study
      of IN and SP in adolescent femoral shaft fractures at a mean age of 13.9 years
      (11-17.4). Twenty-two cases of IN and 23 cases of SP were followed for a minimum
      of 1 year. We compared radiological and clinical results, surgical parameters,
      and complications of two techniques. RESULTS: Bony union was achieved in all
      cases except one case of IN. Time to union was similar in both groups. None
      showed mal-union over 10 degrees  or limb length discrepancy over 1 cm. None of
      SP group and 2 in IN group experienced re-operation; one patient had deep
      infection with nonunion. The other patient sustained mal-rotation. Both patients
      healed after revision procedure. All patients showed excellent or satisfactory
      results of Flynn's criteria. The time to full-weight bearing was shorter in IN
      (IN: 57.3 days, SP: 89.2 days, p<0.05). In surgical parameters, operative time
      seemed shorter in IN (IN: 94.7 min, SP: 104 min, p=0.095), and fluoroscopy time
      was shorter in IN (IN: 58s, SP: 109s, p<0.05) than SP group. CONCLUSION: Although
      both IN and SP yield good results and minimal complication in adolescent femoral
      fractures, IN may be advantageous in less need of fluoroscopy, technical easiness
      in reduction and early weight bearing.

PMID- 22154048
TI  - Rotational bed therapy after blunt chest trauma: a nationwide online-survey on
      current concepts of care in Germany.
AB  - INTRODUCTION: Blunt chest injuries are amongst the most life threatening injuries
      in adult multiple trauma patients. Nevertheless, the treatment of these thoracic
      injuries has not been standardized yet. Previous publications have reported on
      the prevention and the treatment of respiratory complications by using continuous
      lateral rotational bed therapy (CLRT), but there is still a lack of information
      using this approach in the presence of pulmonary contusions. Therefore current
      literature indicates a variety of treatment protocols and its use is contended.
      METHODS: We submitted a 32-item online-questionnaire to 155 hospitals
      participating in the nationwide TraumaNetwork to assess current treatment
      concepts in multiple trauma patients suffering from blunt chest trauma including
      lung contusions with particular focus on the use of CLRT. Overall, 21 level I, 53
      level II and 81 level III trauma centres were contacted. The questionnaire was
      created using "interview 123 5.5.b.de ND6". RESULTS: The overall response rate
      was 35.5% (55/155) and responses were received from 10 level I (47.6%), 17 level
      II (32.1%) and 24 level III (29.6%) trauma centres. Thirty-five of the responders
      (63.6%) declared to be able to perform lateral rotational bed therapy. For level
      I and II trauma centres more than 80% were able to apply kinetic positioning in
      contrast to only 50% of level III trauma centres. Although 42.9% of the
      participants reported on the existence of standardized treatment protocols, 57.1%
      failed to report a standardized operating procedure for CLRT. The annual mean
      number of patients per centre treated via CLRT was 15 (0-130). Treatment
      modalities such as PEEP and the duration of CLRT also showed great variability.
      Against this background three out of four centres declared an urgent need for
      further clinical research in the field. CONCLUSIONS: Our data reflect the wide
      range of different CLRT treatment strategies performed for blunt pulmonary trauma
      involving lung contusions in German trauma centres. We conclude that a high
      quality randomized-controlled trial is warranted to critically assess the role of
      CLRT in multiple trauma patients with blunt chest trauma to provide a sound basis
      for future clinical guidelines.

PMID- 22154049
TI  - Microarray-based mutation detection of pediatric sporadic nonsyndromic hearing
      loss in China.
AB  - OBJECTIVE: To investigate the molecular etiologic causes of sporadic nonsyndromic
      hearing loss in Chinese children. METHODS: 179 sporadic nonsyndromic hearing loss
      children were subjected to microarray-based mutation detection for nine hot spot
      mutations in four of the most common deafness-related genes, including GJB2,
      SLC26A4, GJB3, and 12s rRNA. RESULTS: The incidence of positive genetic errors
      was 43.58% with the current set of target genes in sporadic nonsyndromic hearing
      loss children. Among them, 25.14% of cases had genetic defects in GJB2, 16.76% of
      cases had pathogenic mutations in SLC26A4, 1.12% of cases were caused by 12s rRNA
      mutations, and GJB3 mutation was detected in 0.56% of this group of patients.
      CONCLUSIONS: Our results demonstrated that genetic factors were important causes
      for sporadic nonsyndromic hearing loss in Chinese pediatric cases. Mutations of
      GJB2 and SLC26A4 are two major genetic causes, whereas mutations of GJB3 and 12s
      rRNA result in the development of hearing loss in a small percentage of sporadic
      nonsyndromic hearing loss cases. Microarray testing is a helpful and instrumental
      screening method in the diagnosis of genetic hearing loss.

PMID- 22154050
TI  - EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case
      report.
AB  - Soft tissue myoepithelial tumors, a recently defined entity, include benign and
      malignant lesions showing a considerable morphological and immunohistochemical
      heterogeneity. EWSR1 rearrangements are well recognized in this tumor type, and
      some of the partner genes have been identified. Herein we describe a soft tissue
      myoepithelioma arising in the pelvis with an EWSR1-ATF1 fusion, therefore
      extending the spectrum of partner genes of EWSR1. In addition, this case
      indicates that there are overlapping genetic features of myoepithelial tumors,
      clear cell sarcoma, angiomatoid fibrous histiocytoma, and hyalinizing clear-cell
      carcinoma of the salivary gland.

PMID- 22154051
TI  - Evaluation of the detection of melanin by the Fontana-Masson silver stain in
      tissue with a wide range of organisms including Cryptococcus.
AB  - It is not uncommon for surgical pathologists to encounter yeast and yeast-like
      organisms in tissue sections, and correct identification is imperative for
      guiding therapy. The Fontana-Masson silver stain for detecting melanin has been
      accepted as a relatively specific stain for diagnosing cryptococcosis in tissue
      based on few studies with limited numbers of organisms. This study was designed
      to test the value of the Fontana-Masson silver by investigating a large
      collection of tissues with infections that may mimic cryptococcosis. Cases of
      cryptococcosis and other infections that can morphologically mimic it were
      identified in the pathology archives of The Johns Hopkins Hospital and The Armed
      Forces Institute of Pathology. Overall, Fontana-Masson silver was positive in 25
      (56%) of 45 cases, including infections caused by Cryptococcus neoformans (9/9),
      Coccidioides immitis (7/7), Blastomyces dermatitidis (4/10), Paracoccidioides
      brasiliensis (2/2), Lacazia loboi (1/1), and Rhinosporidium seeberi (1/1). The
      percentage of organisms staining varied widely, from less than 1% to 100%.
      Fontana-Masson silver was negative in all infections caused by Histoplasma
      capsulatum (n = 10), Histoplasma duboisii (n = 1), Sporothrix schenckii (n = 1),
      and the alga genus Prototheca (n = 2). Fontana-Masson silver was 100% sensitive
      for cryptococcosis. The specificity was low, however, with 5 of 9 noncryptococcal
      species being positive in some cases. These results need to be confirmed and
      extended to other isolates and species but it is clear that many organisms in the
      morphological differential diagnosis of cryptococcosis can be Fontana-Masson
      silver stain positive. Accordingly, results of the Fontana-Masson silver stain,
      especially a positive, should be interpreted cautiously and only in the context
      of the organism's morphological features and host factors.

PMID- 22154052
TI  - MAPK7 and MAP2K4 as prognostic markers in osteosarcoma.
AB  - Osteosarcoma is a class of cancer originating from the bone, affecting mainly
      children and young adults. Cytogenetic studies showed the presence of
      rearrangements and recurrent gains in specific chromosomal regions, indicating
      the possible involvement of genes located in these regions during the
      pathogenesis of osteosarcoma. These studies investigated expression of 10 genes
      located in the chromosomal region involved in abnormalities in osteosarcoma,
      1p36, 17p, and chromosome 19. The purpose of this study was to investigate the
      expression profile of genes located in regions involved in chromosomal
      rearrangements in osteosarcoma. We used quantitative real-time polymerase chain
      reaction to investigate the expression of 10 genes located in 1p36.3 (MTHFR,
      ERRFI1, FGR, E2F2), 17p (MAPK7, MAP2K4), and chromosome 19 (BBC3, FOSB, JUND, and
      RRAS), in 70 samples taken from 30 patients (30 prechemotherapy, 30
      postchemotherapy, and 10 metastases specimens) and 10 healthy bones as a control
      sample. The most interesting results showed a strong association between the
      expression levels of MAPK7 and MAP2K4 genes and clinical parameters of
      osteosarcoma. Overexpression of these genes was significantly associated to a
      poor response to treatment (P = .0001 and P = .0049, respectively), tumor
      progression, and worse overall survival (P = .0052 and P = .0085, respectively),
      suggesting that MAPK7 and MAP2K4 could play an important role in osteosarcoma
      tumorigenesis. Thus, these genes could be good markers in assessing response to
      treatment and development of osteosarcoma.

PMID- 22154053
TI  - Erythroid proliferations in myeloid neoplasms.
AB  - Prominent erythroid proliferations (in which erythroid elements comprise >=50% of
      total bone marrow cells) can be seen in various hematopoietic stem cell
      neoplasms. The myeloproliferative neoplasm polycythemia vera exhibits effective,
      overexuberant erythropoiesis resulting in an increased red blood cell mass; in
      contrast, most other diseases characterized by erythroid predominance exhibit
      ineffective hemopoiesis. The latter include acute erythroid leukemia (erythroid
      myeloid and pure erythroid leukemia subtypes) as well as some cases of
      myelodysplastic syndromes, acute myeloid leukemia with myelodysplasia-related
      changes, and therapy-related myeloid neoplasms. Some nonneoplastic reactive
      conditions may also manifest a striking bone marrow erythroid predominance. In
      this article, we review the literature relevant to this group of diseases for a
      better understanding of their clinicopathologic features and surrounding
      controversies. We also examine the position of neoplastic erythroid
      proliferations in the current 2008 World Health Organization Classification of
      Myeloid Neoplasms and provide recommendations as to how to approach the
      differential diagnosis of this group of diseases.

PMID- 22154054
TI  - c-kit gene mutation and CD117 expression in human anorectal melanomas.
AB  - c-kit and BRAF mutations play an important role during the pathogenesis of
      melanoma. The subtypes of melanomas arising from different parts of the body have
      variable c-kit or BRAF mutation frequencies. Few studies in the literature have
      examined c-kit and BRAF mutation status in melanomas that occur in the anus and
      rectum. In this study, we analyzed 40 cases of anorectal melanoma for c-kit and
      BRAF mutations by DNA sequencing using paraffin-embedded tissues. c-kit Mutations
      were detected in exons 9, 11, 13, and 17. CD117 expression in tumor cells was
      analyzed by immunohistochemistry. Our study showed that a c-kit mutation was
      found in 7 of the 40 cases of anorectal melanoma. CD117 expression was detected
      in 16 of the 40 cases, and 3 of these 16 cases also had c-kit mutations.
      Mutations in BRAF were also identified in 2 patients. These results indicate that
      a subset of anorectal melanomas have activating c-kit mutations, which suggests
      that kinase inhibitors such as imatinib may be used to treat this subset of
      melanoma patients. In addition, our results show that c-kit mutations do not
      correlate with CD117 expression.

PMID- 22154055
TI  - Progression of morphological changes after transplantation of a liver with
      heterozygous alpha-1 antitrypsin deficiency.
AB  - Inadvertent transplantation of an alpha-1 antitrypsin-deficient liver into an
      adult man provided a unique opportunity to follow the natural history of
      morphological changes in serial liver biopsies. After doing well initially, the
      patient developed liver function test abnormalities 6 years posttransplant, but
      biopsies at that time and 2 years later revealed only chronic hepatitis with no
      specific features. It was only upon repeat biopsy 10 years posttransplant that
      characteristic cytoplasmic inclusions appeared. Genotypic and phenotypic testing
      of pretransplant and posttransplant specimens confirmed alpha-1 antitrypsin
      deficiency in the transplanted liver. Serologic tests for viral hepatitis and
      autoimmune disease were negative throughout the pretransplant and posttransplant
      period. The case suggests that patients with chronic hepatitis of unknown
      etiology should be tested for the possibility of alpha-1 antitrypsin deficiency
      and illustrates the prolonged course that may precede the development of typical
      cytoplasmic inclusions in the liver.

PMID- 22154056
TI  - Minimally invasive reduction technique in split depression type tibial pilon
      fractures.
AB  - Tibial pilon fractures usually result from high energy trauma and present as a
      challenge to the orthopedic surgeon. Accurate reduction of the joint with
      meticulous care for the surrounding soft tissues is mandatory. We present a case
      report in which an anterior cruciate ligament targeting device is used with a
      minimally invasive technique under arthroscopic and fluoroscopic guidance for
      Orthopaedic Trauma Association 43-B2.3 type pilon fracture treatment.

PMID- 22154057
TI  - Hindfoot plantarflexion: a radiographic aid to the diagnosis of achilles tendon
      rupture.
AB  - Although tendo Achilles (TA) rupture is a clinical diagnosis, radiographs are
      sometimes taken to exclude bony injury. In equivocal clinical examination
      findings, an ultrasound examination is often performed. We investigated whether
      any radiographic signs of TA rupture existed that could help diagnose TA rupture
      in equivocal cases. We examined the case notes of 25 consecutive patients who had
      undergone repair for complete TA rupture. Their lateral radiographs were reviewed
      and the following angles were measured: calcaneal pitch, lateral talocalcaneal,
      and tibiocalcaneal. These were compared with a control group of patients who had
      undergone radiographic examination for ankle injuries resulting in a diagnosis of
      ankle sprain. The results were compared using an unpaired Student's t test. The
      mean tibiocalcaneal angle of the patients with complete TA rupture was 87.0
      compared with 69.4 for the control group (p < .05). No significant difference was
      found with the other angles measured. The tibiocalcaneal angle can be a useful
      adjunct to the clinical examination in the diagnosis of TA rupture. It might also
      have a role in the evaluation of serial cast application after TA repair.

PMID- 22154058
TI  - Radiographic analysis of the Canale view for displaced talar neck fractures.
AB  - Fractures of the talar neck comprise almost 50% of fractures of the talus and may
      result in significant long-term morbidity. It is of paramount importance to
      ensure anatomic reduction of the fracture not only for fracture healing but also
      for minimizing future posttraumatic arthritic sequelae. In addition to
      conventional radiographs and computed tomography scans, the Canale view has
      proven to be beneficial, especially when evaluating for varus displacement. This
      study investigated whether the original method of performing the Canale view
      could be modified for improved evaluation for varus displacement. Simulated talar
      neck fractures were created in 6 cadaveric specimens. These were placed into
      varying amounts of varus displacement; the Canale view was performed with
      progressive degrees of eversion, from 0 degrees  to 25 degrees , resulting in 108
      total views. Blinded evaluation was performed, and a ranking system was used to
      determine the most beneficial degree(s) of eversion for evaluating varus
      malalignment. Multiple statistical analyses were performed. A significant
      difference was seen between the high and low range of values of eversion. A
      significantly lower ranking was achieved with 10 degrees  of eversion. As opposed
      to a single view taken at 15 degrees  of eversion, a range of angles may be most
      beneficial in evaluating varus displacement in talar neck fractures.

PMID- 22154059
TI  - Brodie's abscess of the cuboid in a pediatric male.
AB  - Brodie's abscess of the tarsal cuboid is a rare presentation of a common disease.
      In the present report, we describe the case of Brodie's abscess of the tarsal
      cuboid after a thorn prick in the foot of a 10-year-old boy. The patient was
      asymptomatic in the acute phase of the injury, and on presentation, no evidence
      was found of an open cutaneous wound. The foot radiographs showed a cavitary
      osteolytic lesion in the cuboid bone. Magnetic resonance imaging revealed a
      classic penumbra sign and an abscess in the plantar intrinsic musculature. The
      patient was treated with curettage and debridement combined with broad-spectrum
      antibiotics, which resulted in complete resolution of the symptoms by 6 weeks
      postoperatively. Although microbiologic analysis of the surgical specimen failed
      to reveal a causative microorganism, histopathologic inspection showed chronic
      inflammation, consistent with Brodie's abscess.

PMID- 22154060
TI  - Periprosthetic fracture after femoral intramedullary nail use in two cases of
      tibiotalocalcaneal arthrodesis.
AB  - Tibiotalocalcaneal arthrodesis using intramedullary nail fixation is a
      technically demanding procedure. Periprosthetic fracture in association with
      tibiotalocalcaneal arthrodesis is a rare occurrence, with relatively few
      instances reported. The present report describes 2 such instances that occurred
      after tibiotalocalcaneal arthrodesis using retrograde femoral intramedullary nail
      fixation. Studies have suggested that a longer nail might decrease the incidence
      of periprosthetic fracture. Other factors could also have an influence, including
      the proximal screw orientation and the presence of medical comorbidities, such as
      osteopenia.

PMID- 22154061
TI  - Digital ray transposition for correction of late-stage post toe-to-hand transfer
      forefoot deformity.
AB  - A patient with a painful, severe crossover third toe presented approximately 30
      years after a second toe-to-hand transfer. He was successfully treated with
      multiple digital ray transposition. This procedure can realign the lesser toe,
      close the toe web, and eliminate the need for lifelong use of a toe filler.

PMID- 22154062
TI  - Case of juxta-articular osteoid osteoma of calcaneus mimicking arthritis.
AB  - Juxta-articular osteoid osteoma is a rare disorder that is difficult to correctly
      diagnose at an early stage. We report a case of osteoid osteoma in the calcaneus
      that arose near to the talocalcaneal joint. An 18-year-old female presented with
      symptoms of joint swelling and effusion similar to those of monoarthritis.
      Conservative treatment proved ineffective in achieving pain relief, and she
      underwent surgery 6 months later. The lesion was diagnosed by histologic
      examination, and it resolved after resection of the tumor.

PMID- 22154063
TI  - First crenarchaeal chitinase found in Sulfolobus tokodaii.
AB  - This is the first description of a functional chitinase gene within the
      crenarchaeotes. Here we report of the heterologues expression of the ORF BAB65950
      from Sulfolobus tokodaii in E. coli. The resulting protein degraded chitin and
      was hence classified as chitinase (EC 3.2.4.14). The protein characterization
      revealed a specific activity of 75 mU/mg using colloidal chitin as substrate. The
      optimal activity of the enzyme was measured at pH 2.5 and 70 degrees C,
      respectively. A dimeric enzyme configuration is proposed. According to amino acid
      sequence similarities chitinases are attributed to the two glycoside hydrolase
      families 18 and 19. The derived amino acid sequence of the S. tokodaii gene
      differed from sequences of these two glycoside hydrolase families. However,
      within a phylogenetic tree of protein sequences, the crenarchaeal sequence of S.
      tokodaii clustered in close proximity to members of the glycoside hydrolase
      family 18.

PMID- 22154064
TI  - Case report: atypical presentation of jugular foramen mass.
AB  - INTRODUCTION: Jugular foramen lesions are often associated with pathology of
      adjacent structures due to either compression or direct invasion. Common
      presenting symptoms include pulsatile tinnitus, a neck mass, hearing loss, and
      cranial nerve palsies, leading to changes in taste, vocal cord paralysis,
      dysphagia, and sternocleidomastoid/trapezius weakness (A. Hakuba, K. Hashi, K.
      Fujitani, et al., Jugular foramen neurinomas. Surg Neurol 1979; 11:83-94). This
      patient was found to have a jugular foramen mass after presenting with the
      unusual constellation of visual changes and headache. CASE PRESENTATION: A
      jugular foramen mass in a young woman was discovered after presenting with visual
      changes and headache; the patient was found to have papilledema on initial
      examination. Otologic and head and neck examination were normal. Subsequent
      imaging demonstrated a mass at the right jugular foramen with compression of this
      structure; a contralateral transverse sinus stenosis was also seen. This latter
      abnormality (along with obstruction of the jugular foramen) impeded venous
      drainage leading to papilledema and visual changes. DISCUSSION: In a patient
      presenting with papilledema and severe headache with an associated jugular
      foramen mass, a multidisciplinary approach benefits the patient with input from
      interventional neuroradiology, neurosurgery, and neuro-ophthalmology. Venous
      outflow was compromised through the left stenotic transverse sinus, and the
      normal outflow on the right side through the jugular bulb was impeded by the
      tumor; obstructions of both led to symptomatic impeded venous outflow. This
      compromise in venous outflow led to an increase in superior sagittal sinus
      pressure, with subsequent increase in intracranial pressure and resultant
      papilledema. In an attempt to increase blood flow, an angioplasty was performed
      on the patient's affected transverse sinus. In addition, symptomatology
      consistent with pseudotumor cerebri prompted the use of acetazolamide for medical
      management. After both therapies, the patient's symptoms dramatically improved
      and were stable. The tumor has also remained stable, with no immediate need for
      surgical resection, stereotactic radiation, or consideration of an intraluminal
      transverse sinus stent placement or shunting. CONCLUSION: The unique presentation
      of a jugular foramen mass in a young woman leading to papilledema highlights the
      need for high clinical suspicion of potential etiologies necessary for diagnosis.
      Despite the benign nature of her disease process, an unusual constellation of
      anatomical factors lead to the need for acute intervention.

PMID- 22154065
TI  - Prophylactic valacyclovir in a patient with recurrent vestibular disturbances
      secondary to vestibular neuritis.
AB  - A 57-year-old woman with herpes labialis and previously diagnosed with vestibular
      neuritis experienced recurrences of vertigo and disequilibrium. Initially
      preceded by oral herpes outbreaks or upper respiratory infections, these
      recurrences became spontaneous and more frequent. Vestibular function
      demonstrated a 25% decrease in energy function in the right and the patient had
      left beating nystagmus on positional maneuver. Her reoccurrences of vestibular
      disturbances were followed up. Concurrently, she was prescribed daily
      valacyclovir (500 mg, 1 per day) given for the prevention of herpes labialis
      outbreaks by her primary care physician. Recurrences of disequilibrium stopped
      completely as well as oral herpes outbreaks.

PMID- 22154066
TI  - Quantitative diffusion-weighted magnetic resonance imaging as a powerful adjunct
      to fine needle aspiration cytology for assessment of thyroid nodules.
AB  - OBJECTIVES: The purpose of this study was to assess the value of the apparent
      diffusion coefficient (ADC) in the differential diagnosis between benign and
      malignant thyroid nodules, particularly those found to have indeterminate
      cytology with fine needle aspiration (FNA). METHODS: Thirty-eight patients with
      42 thyroid nodules underwent neck magnetic resonance imaging consisting of T1-,
      T2-, and diffusion-weighted imaging. The final diagnosis of all nodules was
      confirmed by surgery, revealing 23 with benign and 19 with malignant lesions.
      Preoperative FNA cytology was performed in 38 of 42 nodules, including 15 of
      indeterminate cytology. The mean ADC values in benign and malignant groups were
      compared. RESULTS: There was a significant difference between mean ADC values in
      benign and malignant nodules and between mean ADC in benign and malignant nodules
      of indeterminate cytology. A cutoff value for malignant nodules of 1.60 * 10(-3)
      mm(2)/s yielded sensitivity, specificity, and accuracy of 94.73%, 82.60%, and
      88.09%, respectively. CONCLUSION: The present study revealed that ADC
      measurements could potentially quantitatively differentiate between benign and
      malignant thyroid nodules, even those of indeterminate cytology. We propose that
      diffusion-weighted imaging evaluation should be used for the assessment of
      thyroid nodules in addition to FNA cytology.

PMID- 22154067
TI  - Unusual clinical presentation of a partial tibialis anterior rupture.
AB  - Subcutaneous rupture of the tibialis anterior tendon is rare. Diagnosis is
      usually clear. The essential clinical symptoms are progressively: footdrop gait,
      loss of ankle flexion strength, ankle foot pain and claw toes. But the occurrence
      of an asymptomatic time period between the injury and the onset of clinical signs
      can make the diagnosis more difficult. MRI is the gold standard examination for
      tendons injuries and associated bone and joints damages. Surgical exploration
      confirms MRI findings. It constitutes the treatment of choice for tibialis
      anterior tendon rupture. Surgical or functional techniques used have an impact on
      the design of the rehabilitation program, essential step in the care management
      of these injuries. It avoids postoperative tendon adhesions and their functional
      consequences. We report here a case of a man presenting with footdrop gait as the
      only clinical symptom.

PMID- 22154069
TI  - Ultrastructure and morphometry of the egg of Psorophora albigenu Lutz, 1908
      (Diptera: Culicidae).
AB  - Eggs of Psorophora albigenu were analyzed by light and scanning electron
      microscopy. Eggs were laid singly and were black and elliptical in outline. A
      length of approximately 586.4 +/- 10.83 MUm, a width of 172.3 +/- 8.09 MUm
      (n=30), and an egg index (length/width ratio) of 3.33 were observed. The anterior
      extremity tapered abruptly from a width of 64.9 MUm, while such tapering was more
      gradual at the posterior extremity from a width of 77.4 MUm. The ventral surface
      of the chorionic coating presented cells with tubular aspect containing tubercles
      in rows with a density of 9-16 tubercles per cell. These tubercles presented two
      different sizes, with the largest measuring 7.87 +/- 01.58 MUm and the smallest
      measuring 0.71 +/- 0.53 MUm (n=30) in longitudinal diameter. The micropyle
      orifice was very evident, with a diameter of 3.36 MUm. The morphometric
      characteristics of Ps. albigenu obtained in this study were distinct from those
      of other species of the Psorophora genus, including Psorophora varipes which has
      been considered for a long time to be synonymous with Ps. albigenu.

PMID- 22154068
TI  - Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia.
AB  - Deficits in cognitive control, a core disturbance of schizophrenia, appear to
      emerge from impaired prefrontal gamma oscillations. Cortical gamma oscillations
      require strong inhibitory inputs to pyramidal neurons from the parvalbumin basket
      cell (PVBC) class of GABAergic neurons. Recent findings indicate that
      schizophrenia is associated with multiple pre- and postsynaptic abnormalities in
      PVBCs, each of which weakens their inhibitory control of pyramidal cells. These
      findings suggest a new model of cortical dysfunction in schizophrenia in which
      PVBC inhibition is decreased to compensate for an upstream deficit in pyramidal
      cell excitation. This compensation is thought to rebalance cortical excitation
      and inhibition, but at a level insufficient to generate the gamma oscillation
      power required for high levels of cognitive control.

PMID- 22154072
TI  - The high risk HPV16 L2 minor capsid protein has multiple transport signals that
      mediate its nucleocytoplasmic traffic.
AB  - In this study we examined the transport signals contributing to HPV16 L2
      nucleocytoplasmic traffic using confocal microscopy analysis of enhanced green
      fluorescent protein-L2 (EGFP-L2) fusions expressed in HeLa cells. We confirmed
      that both nuclear localization signals (NLSs), the nNLS (1MRHKRSAKRTKR12) and
      cNLS (456RKRRKR461), previously characterized in vitro (Darshan et al., 2004),
      function independently in vivo. We discovered that a middle region rich in
      arginine residues (296SRRTGIRYSRIGNKQTLRTRS316) functions as a nuclear retention
      sequence (NRS), as mutagenesis of critical arginine residues within this NRS
      reduced the fraction of L2 in the nucleus despite the presence of both NLSs.
      Significantly, the infectivity of HPV16 pseudoviruses containing either RR297AA
      or RR297EE within the L2 NRS was strongly reduced both in HaCaT cells and in a
      murine challenge model. Experiments using Ratjadone A nuclear export inhibitor
      and mutation-localization analysis lead to the discovery of a leucine-rich
      nuclear export signal ((462)LPYFFSDVSL) mediating 16L2 nuclear export. These data
      indicate that HPV16 L2 nucleocytoplasmic traffic is dependent on multiple
      functional transport signals.

PMID- 22154073
TI  - First steps of bacteriophage SPP1 entry into Bacillus subtilis.
AB  - The mechanism of genome transfer from the virion to the host cytoplasm is
      critical to understand and control the beginning of viral infection. The initial
      steps of bacteriophage SPP1 infection of the Gram-positive bacterium Bacillus
      subtilis were monitored by following changes in permeability of the cytoplasmic
      membrane (CM). SPP1 leads to a distinctively faster CM depolarization than the
      one caused by podovirus phi29 or myovirus SP01 during B. subtilis infection.
      Depolarization requires interaction of SPP1 infective virion to its receptor
      protein YueB. The amplitude of depolarization depends on phage input and
      concentration of YueB at the cell surface. Sub-millimolar concentrations of
      Ca(2+) are necessary and sufficient for SPP1 reversible binding to the host
      envelope and thus to trigger depolarization while DNA delivery to the cytoplasm
      depends on millimolar concentrations of this divalent cation. A model describing
      the early events of bacteriophage SPP1 infection is presented.

PMID- 22154074
TI  - Smoking history as a predictive factor of treatment response in advanced non
      small-cell lung cancer: a systematic review.
AB  - Recent trials in patients with advanced non-small-cell lung cancer (NSCLC)
      suggest that nonsmokers may benefit more from epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitor (TKI) therapy than will smokers. The aim of this
      systematic review was to assess smoking history as a predictive factor for
      treatment outcomes in patients with NSCLC. Relevant published literature was
      identified through systematic searches of databases (MEDLINE, EMBASE, Cochrane
      Library), oncology and thoracic journals, and abstracts from major oncology
      conferences using prespecified criteria. Articles reporting treatment outcomes
      (overall survival [OS], progression-free survival [PFS], and/or response rate) in
      smoking history subgroups from randomized controlled trials of targeted therapy
      and/or chemotherapy were reviewed. Data from 30 trials (32 articles, 4 abstracts)
      were included. Of these, 23 trials tested first-line therapy. Treatment arms
      included EGFR TKIs (13 trials), EGFR monoclonal antibodies (2 trials), non-EGFR
      targeted treatments (9 trials), chemotherapy (27 trials), and placebo or best
      supportive care only (3 trials). Smoking history definitions and analyses of its
      effect on treatment outcomes varied widely. Only 11 trials reported testing for a
      treatment-by-smoking history interaction. The available evidence supports but
      does not confirm smoking history as a predictive factor for the response to TKIs,
      particularly in previously treated patients. The evidence does not support
      smoking history as a predictor of response to non-EGFR-targeted therapies or
      chemotherapy. Smoking history and its effect on treatment response are
      inadequately reported. More rigorous collection, analysis, and reporting may
      clarify whether smoking history is a predictor of treatment response in advanced
      NSCLC.

PMID- 22154075
TI  - Development and validation of a bioanalytical LC-MS method for the quantification
      of GHRP-6 in human plasma.
AB  - Growth hormone-releasing peptide 6 (GHRP-6, His-(DTrp)-Ala-Trp-(DPhe)-Lys-NH2,
      MW=872.44 Da) is a potent growth hormone secretagogue that exhibits a
      cytoprotective effect, maintaining tissue viability during acute
      ischemia/reperfusion episodes in different organs like small bowel, liver and
      kidneys. In the present work a quantitative method to analyze GHRP-6 in human
      plasma was developed and fully validated following FDA guidelines. The method
      uses an internal standard (IS) of GHRP-6 with 13C-labeled Alanine for
      quantification. Sample processing includes a precipitation step with cold acetone
      to remove the most abundant plasma proteins, recovering the GHRP-6 peptide with a
      high yield. Quantification was achieved by LC-MS in positive full scan mode in a
      Q-Tof mass spectrometer. The sensitivity of the method was evaluated,
      establishing the lower limit of quantification at 5 ng/mL and a range for the
      calibration curve from 5 ng/mL to 50 ng/mL. A dilution integrity test was
      performed to analyze samples at higher concentration of GHRP-6. The validation
      process involved five calibration curves and the analysis of quality control
      samples to determine accuracy and precision. The calibration curves showed R2
      higher than 0.988. The stability of the analyte and its internal standard (IS)
      was demonstrated in all conditions the samples would experience in a real time
      analyses. This method was applied to the quantification of GHRP-6 in plasma from
      nine healthy volunteers participating in a phase I clinical trial.

PMID- 22154076
TI  - Deconstructing p53 transcriptional networks in tumor suppression.
AB  - p53 is a pivotal tumor suppressor that induces apoptosis, cell-cycle arrest and
      senescence in response to stress signals. Although p53 transcriptional activation
      is important for these responses, the mechanisms underlying tumor suppression
      have been elusive. To date, no single or compound mouse knockout of specific p53
      target genes has recapitulated the dramatic tumor predisposition that
      characterizes p53-null mice. Recently, however, analysis of knock-in mice
      expressing p53 transactivation domain mutants has revealed a group of primarily
      novel direct p53 target genes that may mediate tumor suppression in vivo. We
      present here an overview of well-known p53 target genes and the tumor phenotypes
      of the cognate knockout mice, and address the recent identification of new p53
      transcriptional targets and how they enhance our understanding of p53
      transcriptional networks central for tumor suppression.

PMID- 22154077
TI  - Multiple degradation pathways regulate versatile CIP/KIP CDK inhibitors.
AB  - The mammalian CIP/KIP family of cyclin-dependent kinase (CDK) inhibitors (CKIs)
      comprises three proteins--p21(Cip1/WAF1), p27(Kip1), and p57(Kip2)--that bind and
      inhibit cyclin-CDK complexes, which are key regulators of the cell cycle. CIP/KIP
      CKIs have additional independent functions in regulating transcription, apoptosis
      and actin cytoskeletal dynamics. These divergent functions are performed in
      distinct cellular compartments and contribute to the seemingly contradictory
      observation that the CKIs can both suppress and promote cancer. Multiple
      ubiquitin ligases (E3s) direct the proteasome-mediated degradation of p21, p27
      and p57. This review analyzes recent data highlighting our current understanding
      of how distinct E3 pathways regulate subpopulations of the CKIs to control their
      diverse functions.

PMID- 22154078
TI  - Novel therapeutic targets for erectile dysfunction.
AB  - Erectile dysfunction (ED) is a neurovascular phenomenon modulated by hormonal,
      local biochemical, and biomechanical/structural factors of the penis. The success
      of the orally active phosphodiesterase inhibitors for the treatment of ED has
      boosted research activities into the physiology of the erectile mechanism.
      Peripheral intracellular signal transduction in the penis as well as central
      brain and spinal cord pathways controlling penile erection have been investigated
      and are now better understood. The results of this ongoing research have provided
      the basis for the development and introduction of several novel therapeutic
      modalities into the management of ED. Many novel pharmacotherapeutic approaches
      under development including the use of melanocortins and Rho-kinase inhibitors as
      well as the introduction of gene therapy and tissue engineering have demonstrated
      efficacy in animal as well as early human trials. This review describes the major
      new and evolving pharmacological advances in the field of oral pharmacotherapy
      for the treatment of male ED.

PMID- 22154079
TI  - Describing the within laboratory and between laboratory agreement of a serum
      ELISA in a national laboratory network.
AB  - Results from laboratory assays for detection of animal disease are often assessed
      for repeatability (agreement within laboratory) and reproducibility (agreement
      between laboratories). This work aimed to understand the strengths and
      limitations of available methods for describing these quantities. Five major
      veterinary laboratories in Australia volunteered to participate in a designed
      evaluation based on repeat testing of twenty bovine sera. Sampling was stratified
      so that ten of the sera were negative to the virus neutralisation test (VNT) for
      antibody to bovine herpes virus 1 (BHV-1) and the remaining ten sera were VNT
      positive. Each serum was divided into 50 replicates and each laboratory assayed
      one replicate of each serum on a weekly basis using a commercial ELISA for BHV-1.
      Laboratories were blinded to the identity of sera. The data on sample to positive
      control ratio (S/P) for these 1000 individual assays were collated, sources of
      variance analysed using a random effects model, and reliability coefficients
      (rho) obtained from the variance estimates as quantitative measures of within and
      between laboratory agreement. Coefficient of variation (CV) was calculated for
      combinations of sera and laboratory. CV was found to be higher for sera with the
      lowest mean S/P values (VNT -ve sera). For VNT -ve sera, agreement of S/P within
      laboratory was low to moderate (rho: 0.01-0.27) and the agreement between all
      labs was low (rho=0.02). Reliability coefficients for VNT +ve sera were very high
      for agreement within laboratories (rho: 0.63-0.92) and moderate for agreement
      between laboratories (rho=0.52). As well, simulation demonstrated that sero
      prevalence has a dramatic affect on the reliability coefficient if sampling were
      to be irrespective of VNT status. We conclude that there are some limitations
      with the available approaches for assessing agreement within and between
      laboratories. Although reliability coefficients have some drawbacks they are an
      attractive way of reducing reliance on subjective assessment of agreement.

PMID- 22154080
TI  - Long-term bladder function, fertility and sexual function in patients with
      posterior urethral valves treated in infancy.
AB  - OBJECTIVE: To address the issue of sexual function and fertility in PUV patients.
      PATIENTS AND METHODS: Of 47 patients (age > 18 years) treated for PUV in infancy
      28 were contactable. They were sent a standard questionnaire requesting details
      on voiding dysfunction symptoms, and experience of erection, orgasm and
      ejaculation. RESULTS: Of the 28, 16 (mean age 24 years) returned the
      questionnaire. Voiding frequency ranged from 3 to 10 times per day (mean = 5).
      Two patients had occasional mild diurnal incontinence but none had symptoms of
      overactivity. Three patients had a weak urinary stream. Renal function was normal
      in 9, 4 had a glomerular filtration rate <80 ml/min/1.73 m(2), and 3 had
      undergone renal transplant. Erections and orgasm were experienced by the 15
      patients who responded to these questions, with 4 reporting mild or medium
      erectile dysfunction and 1, on dialysis, reporting slow ejaculation. Post
      masturbation samples of semen and urine were collected from 6 patients. One had
      an alkaline pH, high percentage of immotile sperm and low sperm count. Another
      had a high concentration of abnormal forms, and seminal fluid was present in the
      urine of 3 patients. CONCLUSIONS: In long-term follow-up, 44% of PUV patients
      develop chronic renal failure or end-stage renal disease, but bladder dysfunction
      symptoms are infrequent. Sexual function is mostly normal. Total semen counts and
      motility are compatible with paternity in most patients.

PMID- 22154081
TI  - beta2 Agonists enhance the efficacy of simultaneous enzyme replacement therapy in
      murine Pompe disease.
AB  - Enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase
      (rhGAA) has improved clinical outcomes in patients with Pompe disease; however,
      the response of skeletal muscle and the central nervous system to ERT has been
      attenuated. The poor response of skeletal muscle to ERT has been attributed to
      the low abundance of the cation-independent mannose-6-phosphate receptor (CI
      MPR), which mediates receptor-mediated uptake of rhGAA. Hence the ability of
      adjunctive therapy with beta2-agonists to increase CI-MPR expression in skeletal
      muscle was evaluated during ERT in murine Pompe disease with regard to reversal
      of neuromuscular involvement. Mice with Pompe disease were treated with weekly
      rhGAA injections (20 mg/kg) and a selective beta2-agonist, either albuterol (30
      mg/l in drinking water) or low-dose clenbuterol (6 mg/l in drinking water).
      Biochemical correction was enhanced by beta2-agonist treatment in both muscle and
      the cerebellum, indicating that adjunctive therapy could enhance efficacy from
      ERT in Pompe disease with regard to neuromuscular involvement. Intriguingly,
      clenbuterol slightly reduced muscle glycogen content independent of CI-MPR
      expression, as demonstrated in CI-MPR knockout/GAA knockout mice that were
      otherwise resistant to ERT. Thus, adjunctive therapy with beta2 agonists might
      improve the efficacy of ERT in Pompe disease and possibly other lysosomal storage
      disorders through enhancing receptor-mediated uptake of recombinant lysosomal
      enzymes.

PMID- 22154082
TI  - Evaluation of factors predictive of the prognosis in Crimean-Congo hemorrhagic
      fever: new suggestions.
AB  - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is one of the viral
      hemorrhagic fevers caused by tick bites. Common symptoms of the infection are
      fatigue, high fever, headache, and myalgia. In some patients hemorrhage may
      accompany these symptoms and is a sign of a poor prognosis. Typical laboratory
      changes are thrombocytopenia, leukopenia, elevation of aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), and lactate
      dehydrogenase (LDH), and prolongation of prothrombin time (PT) and activated
      partial thromboplastin time (aPTT). Mortality rates vary between 3% and 30%. The
      aim of this study was to determine the factors affecting the prognosis of CCHF.
      METHODS: A total of 70 patients with a diagnosis of CCHF who were followed at our
      clinic between 2005 and 2008 were included in this study. As well as patient
      clinical history, biochemical parameters tested during the first 5 days and the
      prognosis were evaluated. Findings were compared between patients who died and
      those who recovered. Non-parametric statistical tests were used for the
      statistical analysis. RESULTS: When the laboratory parameters of patients who
      died and recovered were compared, PT, aPTT, international normalized ratio (INR),
      AST, LDH, fibrinogen, C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), D
      dimer, IgM, IgG, C3 and C4 levels, and platelet count were found to be positively
      related with fatality. On the other hand, there was no significant difference
      between groups regarding ALT, CPK, prealbumin, ceruloplasmin, protein C, protein
      S, and antithrombin III levels, and white blood cell counts. CONCLUSIONS: It is
      essential to determine the possibility of a fatal prognosis in CCHF patients
      using clinical history and biochemical parameters so that the necessary
      precautions can be taken.

PMID- 22154083
TI  - Vitamin K(3) and K(5) are inhibitors of tumor pyruvate kinase M2.
AB  - Pyruvate kinase M2 (PKM2) is a rate-limiting enzyme of aerobic glycolysis in
      cancer cells and plays important roles in cancer metabolism and growth. Here we
      show that vitamin K(3) and K(5) (VK(3) and VK(5)) are relatively specific PKM2
      inhibitors. VK(3) and VK(5) showed a significantly stronger potency to inhibit
      PKM2 than to inhibit PKM1 and PKL, 2 other isoforms of PK dominantly expressed in
      most adult tissues and liver. This study combined with previous reports supports
      that VK(3) and VK(5) have potential as adjuvant for cancer chemotherapy.

PMID- 22154084
TI  - The LIM domain protein, CRIP2, promotes apoptosis in esophageal squamous cell
      carcinoma.
AB  - The group 2 LIM domain protein, Cysteine-rich intestinal protein 2 (CRIP2) was
      found to play an important role in esophageal squamous cell carcinoma (ESCC)
      tumorigenesis. Subcellular fractionation studies show that CRIP2 is expressed in
      the nucleus. Real-time quantitative PCR shows CRIP2 expression is down-regulated
      in ESCC tissues and cell lines. Functional studies reveal that CRIP2 reduces
      colony formation, growth, and invasion abilities. Furthermore, over-expression of
      CRIP2 induces apoptosis through induction of active caspases 3 and 9 proteins. In
      conclusion, this study shows CRIP2 plays an important role in the development of
      ESCC.

PMID- 22154085
TI  - Cryptotanshinone suppresses androgen receptor-mediated growth in androgen
      dependent and castration resistant prostate cancer cells.
AB  - Androgen receptor (AR) is the major therapeutic target for the treatment of
      prostate cancer (PCa). Anti-androgens to reduce or prevent androgens binding to
      AR are widely used to suppress AR-mediated PCa growth; however, the androgen
      depletion therapy is only effective for a short period of time. Here we found a
      natural product/Chinese herbal medicine cryptotanshinone (CTS), with a structure
      similar to dihydrotestosterone (DHT), can effectively inhibit the DHT-induced AR
      transactivation and prostate cancer cell growth. Our results indicated that 0.5
      MUM CTS effectively suppresses the growth of AR-positive PCa cells, but has
      little effect on AR negative PC-3 cells and non-malignant prostate epithelial
      cells. Furthermore, our data indicated that CTS could modulate AR transactivation
      and suppress the DHT-mediated AR target genes (PSA, TMPRSS2, and TMEPA1)
      expression in both androgen responsive PCa LNCaP cells and castration resistant
      CWR22rv1 cells. Importantly, CTS selectively inhibits AR without repressing the
      activities of other nuclear receptors, including ERalpha, GR, and PR. The
      mechanistic studies indicate that CTS functions as an AR inhibitor to suppress
      androgen/AR-mediated cell growth and PSA expression by blocking AR dimerization
      and the AR-coregulator complex formation. Furthermore, we showed that CTS
      effectively inhibits CWR22Rv1 cell growth and expressions of AR target genes in
      the xenograft animal model. The previously un-described mechanisms of CTS may
      explain how CTS inhibits the growth of PCa cells and help us to establish new
      therapeutic concepts for the treatment of PCa.

PMID- 22154087
TI  - Influence of the enzyme phosphorylation state and the substrate on PKA enzyme
      dynamics.
AB  - cAMP-dependent protein kinase (PKA) is one of the simplest and best understood
      members of the protein kinase family. In a previous study, we have theoretically
      studied the complex between PKA and the heptapeptide substrate Kemptide by
      classical molecular dynamics. On the basis of the results obtained for Kemptide,
      the aim of the present work is to explore how the different conditions, such as
      phosphorylation state, substrate, and mutations of key residues affect the enzyme
      dynamics. We have built different models of the complex; particularly we have
      focused our attention on two crystallographic structures which main difference
      consists in their phosphorylation state. The first one has the residue Thr197
      modified into a phospho-threonine (pThr197); the second one, in addition to the
      same Thr197, has also the residue Ser338 modified into a phospho-serine
      (pSer338). In addition, we have analyzed the effect of the choice of the
      substrate by building a model of the PKA-SP20 Michaelis complex. Finally, we have
      theoretically studied the effect of the mutation of the highly conserved residue
      Asp166 that, experimentally, leads to a decrease of the reaction rate. The
      results of this study give insight into the dynamical states of the enzyme and
      their relationship with different elements of the model, which correspond to
      different natural or human guided situations of the active biological system.

PMID- 22154086
TI  - Characterization of two mouse models of metastatic pheochromocytoma using
      bioluminescence imaging.
AB  - Pheochromocytoma is the most common tumor of the adrenal medulla in adults. The
      lack of sensitive animal models of pheochromocytoma has hindered the study of
      this tumor and in vivo evaluation of antitumor agents. In this study we generated
      two sensitive luciferase models using bioluminescent pheochromocytoma cells: an
      experimental metastasis model to monitor tumor spreading and a subcutaneous model
      to monitor tumor growth and spontaneous metastasis. These models offer a platform
      for sensitive, non-invasive and real-time monitoring of pheochromocytoma primary
      growth and metastatic burden to follow the course of tumor progression and for
      testing relevant antitumor treatments in metastatic pheochromocytoma.

PMID- 22154088
TI  - Iberomaurusian funerary behaviour: evidence from Grotte des Pigeons, Taforalt,
      Morocco.
AB  - Grotte des Pigeons at Taforalt, north-east Morocco, is well known for a large
      assemblage of Iberomaurusian (Epipalaeolithic) skeletons, possibly representing
      the earliest and most extensively used prehistoric cemetery in North Africa. New
      archaeological excavations carried out in 2005 and 2006 revealed further human
      remains in a largely undisturbed burial area in an alcove at the back of the
      cave. This discovery provides the first opportunity to report on Iberomaurusian
      human mortuary activity at this site. Reported here are a closely spaced and
      inter-cutting series of four burials. These contained the remains of four adults,
      of which three were buried in a seated or slightly reclining position facing
      towards the cave entrance and one was buried in a highly flexed position on its
      left side. The distribution of articulated and disarticulated bones suggested
      intensive use of the area, with earlier burials disturbed or truncated by
      subsequent burials, and displaced skeletal elements deliberately or unwittingly
      incorporated into later depositions. Through this process, parts of a single
      skeleton were redistributed among several discrete graves and within the
      surrounding deposit. Some aspects of the Iberomaurusian funerary tradition that
      are evident from the human remains excavated in the 1950s are absent in the newly
      excavated adult burials, suggesting a possible elaboration of funerary activity
      over time.

PMID- 22154089
TI  - Effect of Hurricane Katrina on incidence of acute myocardial infarction in New
      Orleans three years after the storm.
AB  - To detect a long-term increase in the incidence of acute myocardial infarction
      (AMI) after Hurricane Katrina and to investigate the pertinent contributing
      factors, we conducted a single-center retrospective cohort observational study.
      The patients admitted with AMI to Tulane University Hospital in the 2 years
      before Katrina and the 3 years after the hospital reopened were identified from
      the hospital medical records. The pre- and post-Katrina groups were compared for
      prespecified demographic and clinical data. In the 3-year post-Katrina group, 418
      admissions (2.0%) for AMI occurred of a total census of 21,092 patients compared
      to 150 (0.7%) of a census of 21,079 in the 2-year pre-Katrina group (p <0.0001).
      The post-Katrina group had a greater prevalence of unemployment (p <0.0001), lack
      of medical insurance (p <0.001), smokers (p <0.01), medical noncompliance (p
      <0.0001), first-time hospitalizations (p <0.001), history of coronary artery
      disease (p <0.01), multiple vessel disease (p <0.05), and percutaneous coronary
      interventions (p <0.0001). The mean age of onset of AMI decreased from 62 years
      before Katrina to 59 years after Katrina (p <0.05), and a significantly greater
      percentage of patients were men (p <0.05). No significant differences were found
      between the two groups in terms of race, substance abuse, and a history of
      hypertension or diabetes mellitus. Our data suggest that chronic stress after
      natural disasters may significantly affect cardiovascular risk factors such as
      tobacco abuse and increase medical noncompliance. In conclusion, our data is
      consistent with a significant change in the overall health of the population and
      support the need for additional study into the health effects of chronic stress
      after natural disasters.

PMID- 22154091
TI  - Attention and consciousness: related yet different.
AB  - A recent perceptual imaging experiment uses a rare 2*2 design to dissociate
      selective visual attention from visual consciousness. Its conclusions support the
      hypothesis that visual consciousness does not arise from neurons in primary
      visual cortex and forces a reinterpretation of numerous prior studies.

PMID- 22154090
TI  - Relation between digital peripheral arterial tonometry and brachial artery
      ultrasound measures of vascular function in patients with coronary artery disease
      and in healthy volunteers.
AB  - Digital peripheral arterial tonometry (PAT) is an emerging, noninvasive method to
      assess vascular function. The physiology underlying this phenotype, however,
      remains unclear. Therefore, we evaluated the relation between digital PAT and
      established brachial artery ultrasound measures of vascular function under basal
      conditions and after reactive hyperemia. Using a cross-sectional study design,
      digital PAT and brachial artery ultrasonography with pulsed wave Doppler were
      simultaneously completed at baseline and after reactive hyperemia in both those
      with established coronary artery disease (n = 99) and healthy volunteers with low
      cardiovascular disease risk (n = 40). Under basal conditions, the digital pulse
      volume amplitude demonstrated a significant positive correlation with the
      brachial artery velocity-time integral that was independent of the arterial
      diameter, in both the healthy volunteer (r(s) = 0.64, p <0.001) and coronary
      artery disease (r(s) = 0.63, p <0.001) cohorts. Similar positive relations were
      observed with the baseline brachial artery blood flow velocity and blood flow. In
      contrast, no relation between the reactive hyperemia-evoked digital PAT ratio and
      either brachial artery flow-mediated dilation or shear stress was observed in
      either cohort (p = NS). In conclusion, these findings demonstrate that the
      digital PAT measures of vascular function more closely reflect basal blood flow
      in the brachial artery than reactive hyperemia-induced changes in the arterial
      diameter or flow velocity, and the presence of vascular disease does not modify
      the physiology underlying the digital PAT phenotype.

PMID- 22154092
TI  - Successful management of rocuronium-induced anaphylactic reactions with
      sugammadex: a case report.
AB  - Sugammadex, a new reversal agent for rocuronium, encapsulates the rocuronium
      molecule and results in rapid reversal of rocuronium-induced neuromuscular
      blockade. A case in which sugammadex was used to treat an anaphylactic reaction
      that occurred after rocuronium is presented. The binding/encapsulation of
      rocuronium by sugammadex may selectively eliminate the antigenic quaternary
      ammonium activity of circulating rocuronium, and prevent the propagation of
      rocuronium-induced anaphylaxis.

PMID- 22154093
TI  - Does anesthetic technique influence cancer?

PMID- 22154094
TI  - Help-seeking and coping with the psychosocial burden of chronic hepatitis C: a
      qualitative study of patient, hepatologist, and counsellor perspectives.
AB  - BACKGROUND: Chronic hepatitis C affects millions of people worldwide, may have
      significant physical consequences, and patients are also at increased risk of
      psychiatric morbidity. However, it is currently unknown how patients cope with,
      and seek help for the psychosocial issues which contribute to this psychiatric
      morbidity. OBJECTIVES: This study aimed to qualitatively explore the
      biopsychosocial burden of chronic hepatitis C, patients' subsequent coping and
      help-seeking, and the patient-health professional relationship from the different
      perspectives of patients, hepatologists, and counsellors. METHODS: Thirteen
      patients, five hepatologists, and two hepatitis C specific counsellors from South
      Australia participated in semi-structured interviews, which were audio-recorded,
      transcribed verbatim, and analysed thematically. RESULTS: All groups perceived
      chronic hepatitis C as a severe disease involving inextricably intertwined
      biological, psychological, and social impacts. Negative factors included the
      impact of diagnosis, stigmatisation, and often unwarranted fears regarding
      transmission and disease progression. The key positive influences reported across
      the groups involved information provision and access to informal and formal
      support. However, a number of barriers were noted to accessing this support,
      particularly stigmatisation. All respondents highlighted the importance of the
      patient-health professional relationship. This relationship was perceived to be
      enhanced by empathetic, compassionate professionals who provided comprehensive
      information in a sensitive and timely manner. Key negative influences on this
      relationship included discrimination or inappropriate treatment from mainstream
      health professionals, time constraints of doctors, patient non-attendance, and
      discordant views regarding treatment decisions. CONCLUSIONS: Reducing the
      psychosocial impact of chronic hepatitis C requires targeted information
      provision for patients, the general public, and mainstream health services. This
      may increase patient education, reduce the extent and impact of stigmatisation,
      remove barriers to help-seeking, and improve the patient-health professional
      relationship.

PMID- 22154095
TI  - Factors influencing self-management in chronic obstructive pulmonary disease: an
      integrative review.
AB  - BACKGROUND: Chronic obstructive pulmonary disease is a common, chronic and
      burdensome condition requiring the individual to engage in a range of self
      management strategies. The capacity to engage in self-management is dependent on
      a range of internal (e.g., personal) and external (e.g., health service) factors.
      OBJECTIVES: This paper seeks to define self-management, identify the determinants
      which influence the individual's ability to cope and adjust to living with
      chronic obstructive pulmonary disease in the community, and identify implications
      for clinical practice and research. DESIGN: Integrative review. DATA SOURCES:
      Medline, Embase, PubMed, CINAHL, Google Scholar. REVIEW METHODS: Integrative
      review using prospective research questions. Papers were included in the review
      if they were published in peer reviewed journals and written in English between
      2000 and 2010. Articles were accepted for inclusion if they discussed the
      determinants that influenced self-management of chronic obstructive pulmonary
      disease in the community. Confirmation of results and discussion themes was
      validated by specialists in chronic obstructive pulmonary disease and complex
      care. FINDINGS: Self-management is less well characterised in chronic obstructive
      pulmonary disease compared with other chronic conditions. Functional limitation
      and the need to balance disease management with everyday life are the two key
      elements that patients face in managing their condition. Provider
      characteristics, socioeconomic status and health literacy are sparsely discussed
      yet are known to influence chronic obstructive pulmonary disease self-management.
      CONCLUSIONS: Chronic obstructive pulmonary disease self-management must be a key
      focus internationally as the disease incidence increases. Collaborative care is
      required between patients and health providers in order facilitate patients in
      confident management of their condition.

PMID- 22154096
TI  - Monolayer and Brewster angle microscopy study of human serum albumin-dipalmitoyl
      phosphatidyl choline mixtures at the air-water interface.
AB  - The aim of this study is to deepen the understanding of the behavior of human
      serum albumin (HSA) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) mixed
      monolayers. For this purpose, different amounts of DPPC were spread at 25 degrees
      C on the water surface containing a monolayer of HSA. Surface film balance and
      Brewster angle microscopy techniques have been used to analyze the structural and
      energetic characteristics (structure, topography, thickness, miscibility and
      interactions) of these mixtures. HSA/DPPC mixed monolayers exhibit two phase
      transitions evidenced by two discontinuities in the corresponding pi-A isotherms
      and by two minimum values in the compressional modulus (C(s)(-1))-surface
      pressure (pi) curves. The plot of the molecular areas occupied by the mixed
      monolayers as function of the mass fraction of DPPC shows the absence of
      deviations from linearity, a typical behavior for ideal or inmiscible system.
      This result was confirmed from the values calculated for the free energy of
      excess (DeltaG(exc)), which are practically zero whatever the composition of the
      mixtures and the surface pressures at which DeltaG(exc) values were calculated.
      In addition, relative thickness values of HSA/DPPC mixed monolayers showed the
      existence of an exclusion surface pressure (pi(exc)), below which the monolayer
      is composed of a mixture of both components, while above pi(exc) the HSA
      molecules are squeezed out the interface, but not totally. In fact, although in
      this region DPPC domains predominate at the interface, the existence of protein
      molecules in a packing "loops" configuration can be observed in BAM images.
      Moreover, relative thickness measurements confirm this hypothesis.

PMID- 22154097
TI  - Sum frequency generation study on the structure of water in the vicinity of an
      amphoteric polymer brush.
AB  - A polyampholyte brush was prepared on the surface of a quartz prism by surface
      initiated reversible addition-fragmentation chain-transfer polymerization of
      methacrylic acid (MA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) at a
      monomer ratio of 1:1. The sum frequency generation method indicated that water
      molecules at the amphoteric polymer brush-water interfaces were not greatly
      oriented in comparison with those at the surfaces of bare quartz prisms, and
      negatively charged PolyMA and positively charged PolyDMAEMA brushes. The small
      perturbation effect of an amphoteric polymer brush on the structure of vicinal
      water was in accordance with the tendency of aqueous solution and thin films of
      amphoteric polymers observed by using Raman and infrared spectroscopies,
      respectively.

PMID- 22154098
TI  - Graphite grains studded with silver nanoparticles: description and application in
      promoting direct biocatalysis between heme protein and the resulting carbon paste
      electrode.
AB  - The impregnation of graphite grains with silver nanoparticles (AgNPs) is proposed
      for making a novel carbon paste electrode (CPE). The resulting material promotes
      direct electron transfer and direct biocatalysis of embedded heme protein. It is
      demonstrated that the impregnation of graphite grains with AgNPs of 16-25 nm,
      incorporated in a CPE, can promote measurable bio-electrochemical phenomena
      involving hemoglobin and myoglobin. Unlike other biosensors prepared with simple
      carbon, those based on carbon grains studded with AgNPs show well-defined and
      quasi-reversible voltammetric peak with heterogeneous electron transfer rate k(s)
      of approximately 0.037+/-0.007 and 0.013+/-0.005s(-1) for hemoglobin and
      myoglobin, respectively. The embedded proteins also retain their bio-catalytical
      activity for hydrogen peroxide and nitrite reduction with linear ranges of 0.5
      3000 MUM and 30-150 MUM, sensitivities of 73.6+/-0.6nA MUM(-1) and 5.72+/-0.11 nA
      MUM(-1), and detection limits close to 0.08 MUM and 5.80 MUM, for these two
      analytes respectively. These results support the viability of this preliminary
      approach for the development of advanced third-generation biosensors.

PMID- 22154099
TI  - Bio-plastic (P-3HB-co-3HV) from Bacillus circulans (MTCC 8167) and its
      biodegradation.
AB  - Polyhydroxyalkanoates (PHAs) are naturally occurring polyesters synthesized by
      bacteria for carbon and energy storage and it has commercial potential as
      bioplastic. The bacterial species Bacillus circulans MTCC 8167, isolated from
      crude oil contaminated soil, can efficiently produce medium chain length
      polyhydroxyalkanoates (P-3HB-co-3HV) from cheap carbon sources like dextrose. The
      molecular mass of P-3HB-co-3HV was reported as 5.1*10(4)Da with polydispersity
      index of 1.21 by gel permeation chromatography. In the present investigation
      different bacteria and fungi species were used for testing the biodegradability
      of the extracted polymer. The FTIR spectra of the biodegraded PHBV film showed a
      decrease in the peak from 1735 cm(-1) (untreated film) to 1675 cm(-1), and
      disappearance of a peak present in the control at 2922 cm(-1) indicating the
      breakdown of ester (>C=O) or O-R group and -C=H bond, respectively. From
      biodegradability testing, the tested microorganisms were found to have decisive
      contribution to the biodegradation of P-3HB-co-3HV polymer.

PMID- 22154100
TI  - Enhanced transdermal delivery of indomethacin using combination of PLGA
      nanoparticles and iontophoresis in vivo.
AB  - Nanoparticles effectively deliver therapeutic agent by penetrating into the rat
      skin in vivo. Indomethacin (IM) and coumarin-6 were loaded in PLGA nanoparticles
      with an average diameter of 100 nm. Indomethacin (IM) and coumarin-6 were chosen
      as a model drug and as a fluorescent marker, respectively. The surfaces of the
      nanoparticles were negatively charged. Permeability of IM-loaded PLGA
      nanoparticles through rat skin was studied in vivo. Higher amount of IM was
      delivered through skin when IM was loaded in nanoparticles than IM was free
      molecules. Also, iontophoresis was applied to enhance the permeability of
      nanoparticles. When iontophoresis was applied at 0.05 mA/cm(2), permeability of
      IM was much higher than that obtained by simple diffusion of nanoparticles
      through skin. The combination of charged nanoparticle system with iontophoresis
      is useful for effective transdermal systemic delivery of therapeutic agents.

PMID- 22154101
TI  - Compliance with standard precautions among gastrointestinal endoscopists and
      endoscopy nurses in Japan.

PMID- 22154102
TI  - [Guillain-Barre syndrome in a child with normal tendon reflexes].
AB  - We describe the case of a 10-year-old child with the acute motor axonal
      neuropathy (AMAN) form of Guillain-Barre syndrome (GBS) with preserved tendon
      reflexes, 6 days after a bout of gastroenteritis. The child quickly showed
      weakness of the distal muscles of his four limbs, with preserved tendon reflexes
      and a raised CSF protein concentration with no cells. Nerve conduction studies
      showing motor axonal degeneration confirmed the diagnosis of GBS in spite of
      preserved tendon reflexes. The serum was positive for IgG antibodies to
      gangliosides GM1 and GD1b. The child received intravenous immunoglobulins, which
      resulted in a favorable progression. This case proves that GBS with normal tendon
      reflexes exists. The other cases of SGB with preserved tendon reflexes already
      described in the literature were the AMANs form with antibodies to gangliosides
      in the serum and only adults were affected.

PMID- 22154103
TI  - Genetic variability in IL23R and risk of colorectal adenoma and colorectal
      cancer.
AB  - Inflammatory processes, including, specifically, the inflammatory conditions
      Crohn's disease (CD) and ulcerative colitis (UC) predispose to colorectal cancer.
      Interleukin-23 is involved in pro-inflammatory signaling; genetic variation in
      the interleukin-23 receptor (IL23R) has been consistently associated with CD and
      UC risk. In three case-control studies of colorectal adenoma (n=485 cases/578
      controls), colon cancer (n=1424 cases/1780 controls) and rectal cancer (n=583
      cases/775 controls), we investigated associations with 18 candidate and tagSNPs
      in IL23R. The three studies used an identical Illumina GoldenGate assay, allowing
      thorough investigation across stages and locations of colorectal neoplasia. We
      further explored associations with molecular cancer subtypes (MSI+, CIMP+,
      KRAS2mut, TP53mut). In this comprehensive study of genetic variability in IL23R
      across the spectrum of colorectal carcinogenesis, as well as within colon and
      rectal tumor molecular subtypes, we observed associations between SNPs in IL23R
      and risk of rectal cancer: the 88413 C>A (rs10889675) and 69450 C>A (rs7542081)
      polymorphisms were associated with decreased rectal cancer risk overall (p
      trend=0.04 and 0.05 respectively), and specifically with rectal tumors bearing a
      TP53 mutation (88413 CA/AA vs. CC OR: 0.66; 95% CI: 0.46-94; 69450 CA/AA vs. CC
      OR: 0.60; 95% CI: 0.37-0.98). However, none of associations remained
      statistically significant after correction for multiple testing. These data
      provide some evidence that genetic variability in IL23R may contribute to rectal
      cancer risk and should be evaluated in additional studies.

PMID- 22154104
TI  - Reconstruction of the X-ray tube spectrum from a scattering measurement.
AB  - An inverse technique has been designed to unfold the x-ray tube spectrum from the
      measurement of the photons scattered by a target interposed in the path of the
      beam. A special strategy is necessary to circumvent the ill-conditioning of the
      forward transport algebraic problem. The proposed method is based on the
      calculation of both, the forward and adjoint analytical solutions of the
      Boltzmann transport equation. After testing the method with numerical
      simulations, a simple prototype built at the Operational Unit of Health Physics
      of the University of Bologna was used to test the method experimentally. The
      reconstructed spectrum was validated by comparison with a straightforward
      measurement of the X-ray beam. The influence of the detector was corrected in
      both cases using standard unfolding techniques. The method is capable to
      accurately characterize the intensity distribution of an X-ray tube spectrum,
      even at low energies where other methods fail.

PMID- 22154105
TI  - Semi-automated potentiometric titration method for uranium characterization.
AB  - The manual version of the potentiometric titration method has been used for
      certification and characterization of uranium compounds. In order to reduce the
      analysis time and the influence of the analyst, a semi-automatic version of the
      method was developed in the Brazilian Nuclear Energy Commission. The method was
      applied with traceability assured by using a potassium dichromate primary
      standard. The combined standard uncertainty in determining the total
      concentration of uranium was around 0.01%, which is suitable for uranium
      characterization.

PMID- 22154106
TI  - Improvement of RNA-SIP by pyrosequencing to identify putative 4-n-nonylphenol
      degraders in activated sludge.
AB  - Nonylphenols (NP) have estrogenic potential because of their phenolic ring, but
      the organisms involved in the degradation of this alkylated phenol remain
      unidentified. Using 16S ribosomal RNA (rRNA)-based stable isotope probing (SIP)
      and a new method based on pyrosequencing, we identified the bacteria involved in
      the degradation of the aromatic ring of [U-ring-(13)C] 4-n-NP in aerobic sludge.
      The first order degradation rate of 4-n-NP was 5.5d(-1). Single strand
      conformation polymorphism of density-separated labeled and unlabeled 16S rRNA
      showed significant differences and enabled selection of four representative
      fractions for pyrosequencing. Nineteen phylotypes showed a significant enrichment
      in the heavy fraction in the labeled pulse. The relative abundances of these
      phylotypes were combined with the RNA concentration of each fraction to yield a
      simple model of the distribution of each phylotype across the gradient. This
      model was used to estimate the percentage of labeling for each phylotype. The
      sequences showing the highest labeling (11%) were closely related to Afipia sp.
      but represented only 2 % of the RNA in the heavy fraction of the labeled pulse.
      The sequences representing the largest proportion of the RNA in the heavy
      fraction were related to Propionibacterium acnes and Frateuria aurantia, which
      are known to possess enzymes for phenol degradation. The model shows that despite
      Afipia having the highest (13)C enrichment, other species encoding phenol
      degradation pathways are responsible for more (13)C incorporation. Last, we
      showed that some species represent 12% of the total RNA but contain only 1% (13)C
      above natural abundance.

PMID- 22154107
TI  - Perfluoroalkyl acids in urban stormwater runoff: influence of land use.
AB  - Perfluoroalkyl acids (PFAAs) are persistent organic pollutants in the environment
      and have been reported to have nonpoint sources. In this study, six PFAAs with
      different chain lengths were monitored in stormwater runoff from seven storm
      events (2009-2011) at various outfall locations corresponding to different
      watershed land uses. We found PFAA(s) in 100% of stormwater runoff samples.
      Monitoring results and statistical analysis show that PFAAs in stormwater runoff
      from residential areas mainly came from rainfall. On the other hand, non
      atmospheric sources at both industrial and commercial areas contributed PFAAs in
      stormwater runoff. The mass flux of PFAAs from stormwater runoff in the Twin
      Cities (Minneapolis and St. Paul, MN) metropolitan area is estimated to be about
      7.86 kg/year. In addition, for the first time, we monitored PFAAs on the
      particles/debris in stormwater runoff and found high-level PFOS on the
      particulate matter in runoff collected from both industrial and commercial areas;
      the levels were so high that the finding could not be explained by the solid
      water partitioning or adsorption. PFOS on the particulate matter is suspected to
      have originated from industrial/commercial products, entering the waste stream as
      PFOS containing particles.

PMID- 22154108
TI  - Effects of chromium on activated sludge and on the performance of wastewater
      treatment plants: A review.
AB  - Chromium is a heavy metal of commercial importance, thus significant amounts are
      released in wastewaters. Chromium in wastewaters and in the aquatic environment
      is primarily encountered in oxidation stages +3 (Cr((III))) and +6 (Cr((VI))).
      Recent publications suggest that Cr((VI)) compounds are more toxic than Cr((III))
      ones, while Cr((III)) has been identified as trace element, at least for complex
      organisms. With respect to chromium species mobility, Cr((VI)) can cross cellular
      membranes, which then may be oxidized to Cr((III)) and react with intracellular
      biomolecules. Clear conclusions cannot be derived about the critical chromium
      concentrations that affect activated sludge growth, as the latter is a function
      of a number of factors. Broadly, may be supported that activated sludge growth is
      stimulated at Cr((III)) concentrations up to 15 mg L(-1), above which is
      inhibited, with lethal doses lying above 160 mg Cr((III)) L(-1). On the other
      hand, literature data on Cr((VI)) effects on activated sludge are even more
      controversial. A number of reports support that Cr((VI)) is toxic to activated
      sludge at concentrations above 5 mg L(-1), while others report growth stimulation
      at concentrations up to 25 mg L(-1). However, all reports agree that Cr((VI)) is
      definitely an activated sludge growth inhibitor at higher concentrations, while
      80 mg Cr((VI)) L(-1) have been identified as lethal dose. A number of factors
      have been identified to influence chromium toxicity on activated sludge, such as,
      pH, biomass concentration, presence of organic substances or other heavy metals,
      acclimation process, exposure time, etc. Naturally, the presence of chromium
      species in wastewaters may affect the performance of wastewater treatment plants
      often causing malfunctions, particularly for industrial wastewaters containing
      relatively high chromium concentrations. The present work reviews in a critical
      way the published literature on chromium effects on activated sludge, and on the
      operation of wastewater treatment plants.

PMID- 22154109
TI  - Enhanced mitigation of para-chlorophenol using stratified activated carbon
      adsorption columns.
AB  - The adsorptive removal of toxic para-chlorophenol using activated carbon
      adsorption columns is a proven effective engineering process. This paper examined
      the possibility to stratify an adsorbent bed into layers, in order to enhance the
      adsorption process performance in terms of increased column service time and
      adsorbent bed saturation. Four different types of fixed-bed adsorption columns
      are used and compared under the same operating conditions, but with the variation
      of column geometry and activated carbon particle size stratification. The Type 3
      column - a cylindrical column with particle stratification packing, is found to
      be the most efficient choice, as the extent of column service time and adsorbent
      bed saturation are the largest. This could eventually decrease the frequency of
      adsorbent replacement/regeneration and hence reduce the operating cost of the
      fixed-bed adsorption process. The Homogeneous Surface Diffusion Model (HSDM) was
      applied successfully to describe the dynamic adsorption of para-chlorophenol onto
      Filtrasorb 400 (F400) activated carbon in different types of columns. The Redlich
      Peterson isotherm model equation, an experimentally derived external mass
      transfer correlation and a constant surface diffusivity are used in the HSDM. The
      optimised surface diffusivity of para-chlorophenol is found to be 1.20E-8
      cm(2)/s, which is in good agreement with other phenolics/F400 carbon diffusing
      systems in literature.

PMID- 22154110
TI  - Identification of ozonation by-products of 4- and 5-methyl-1H-benzotriazole
      during the treatment of surface water to drinking water.
AB  - During the treatment of surface water to drinking water, ozonation is often used
      for disinfection and to remove organic trace substances, whereby oxidation by
      products can be formed. Here we use the example of tolyltriazole to describe an
      approach for identifying relevant oxidation by-products in the laboratory and
      subsequently detecting them in an industrial-scale process. The identification
      process involves ozonation experiments with pure substances at laboratory level
      (concentration range mg L(-1)). The reaction solutions from different ozone
      contact times were analyzed by high performance liquid chromatography -
      quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) in full scan mode.
      Various approaches were used to detect the oxidation by-products: (i) target
      searches of postulated oxidation by-products, (ii) comparisons of chromatograms
      (e.g., UV/VIS) of the different samples, and (iii) color-coded abundance time
      courses (kinetic) of all detected compounds were illustrated in a kind of a heat
      map. MS/MS, H/D exchange, and derivatization experiments were used for structure
      elucidation for the detected by-product. Due to the low contaminant
      concentrations (ng L(-1)-range) of contaminants in the untreated water, the
      conversion of results from laboratory experiments to an industrial-scale required
      the use of HPLC-MS/MS with sample enrichment (e.g., solid phase extraction.) In
      cases where reference substances were not available or oxidation by-products
      without clear structures were detected, reaction solutions from laboratory
      experiments were used to optimize the analytical method to detect ng L(-1) in the
      samples of the industrial processes. We exemplarily demonstrated the
      effectiveness of the methodology with the industrial chemicals 4- and 5-methyl-1H
      benzotriazole (4- and 5-MBT) as an example. Moreover, not only did we identify
      several oxidation by-products in the laboratory experiments tentatively, but also
      detected three of the eleven reaction products in the outlet of the full-scale
      ozonation unit.

PMID- 22154111
TI  - Adsorption of perchlorate and other oxyanions onto magnetic permanently confined
      micelle arrays (Mag-PCMAs).
AB  - The removal of oxyanions found in drinking water sources -perchlorate, nitrate,
      phosphate, and sulfate- onto magnetic permanently confined micelle arrays (Mag
      PCMAs) was studied. We determined the removal efficiency in both competitive and
      non-competitive environments, as many of these anions are present in these
      sources. Mag-PCMA removed over 98% of the aqueous perchlorate anions across a
      concentration range of 60-500 MUg/L. Nitrate was absorbed 100% over a
      concentration range of 10-35 mg/L as nitrate. Removal of phosphate was 95.7% for
      0.2-2.45 mg/L as phosphate. Sulfate was 100% absorbed across a concentration
      range of 5-20 mg/L and an average 75.7% for 5-50 mg/L. The sorption isotherms
      followed a Freundlich relationship with K(f) values of 2.00, 2.05, 1.9, and 3.86
      mg/g for nitrate, perchlorate, phosphate, and sulfate respectively. Perchlorate
      and nitrate did not compete significantly for binding on Mag-PCMAs, with almost
      equal sorption, greater than 90%, for both anions in elevated concentrations.
      This is a distinguishing feature from ion exchange resins or activated carbon
      with cationic surfactants, where these anions have been shown to compete for
      sorption sites. At the concentrations studied, phosphate and sulfate also do not
      exhibit significant competition. Desorption for reuse was successful at pH 10.
      This reusable magnetic sorbent can thus be used to rapidly remove target anions
      such as perchlorate from water in the presence or absence of other oxyanions.

PMID- 22154112
TI  - Development of antifouling reverse osmosis membranes for water treatment: A
      review.
AB  - With the rapidly increasing demands on water resources, fresh water shortage has
      become an important issue affecting the economic and social development in many
      countries. As one of the main technologies for producing fresh water from saline
      water and other wastewater sources, reverse osmosis (RO) has been widely used so
      far. However, a major challenge facing widespread application of RO technology is
      membrane fouling, which results in reduced production capacity and increased
      operation costs. Therefore, many researches have been focused on enhancing the RO
      membrane resistance to fouling. This paper presents a review of developing
      antifouling RO membranes in recent years, including the selection of new starting
      monomers, improvement of interfacial polymerization process, surface modification
      of conventional RO membrane by physical and chemical methods as well as the
      hybrid organic/inorganic RO membrane. The review of research progress in this
      article may provide an insight for the development of antifouling RO membranes
      and extend the applications of RO technology in water treatment in the future.

PMID- 22154113
TI  - Overcoming molecular mechanisms of resistance to first-generation epidermal
      growth factor receptor tyrosine kinase inhibitors.
AB  - The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)
      gefitinib and erlotinib have provided substantial benefits to patients with
      advanced non-small cell lung cancer (NSCLC). However resistance to these agents
      has emerged as a significant clinical issue; most patients who initially respond
      to treatment eventually experience relapse. The mechanisms underlying gefitinib
      and erlotinib resistance are multifactorial and several have been described.
      Clearly there is a need for novel and more effective therapies that can overcome
      resistance to the currently available TKIs. Several agents are in clinical
      development, including irreversible EGFR TKIs, inhibitors of the MET pathway, and
      others. In this review we discuss the various underlying mechanisms of gefitinib
      and erlotinib resistance and highlight the agents currently in clinical
      development that may have potential for overcoming this resistance.

PMID- 22154114
TI  - Long-term evaluation of gait initiation in six Parkinson's disease patients with
      bilateral subthalamic stimulation.
AB  - Defined as the transient state between standing and walking, gait initiation is
      negatively affected in Parkinson's disease (PD), which often results in
      significant disability. Although deep brain stimulation (DBS) is the most common
      surgical procedure for PD, the long-term effects of DBS on gait initiation are
      not well studied. The present study evaluated the long-term effects of
      subthalamic nucleus (STN) DBS on the preparation phase of gait initiation using
      principal component (PC) analysis. Six patients with PD who had undergone STN DBS
      and 24 healthy control subjects were evaluated. PD subjects were assessed 11.3+/
      10.3 (P1) and 78.9+/-10.6 (P2) months after surgery. PD subjects were tested with
      STN DBS in two conditions: without medication and with medication. PC analysis
      was applied separately for the vertical, anterior-posterior and medial-lateral
      components of ground reaction force (GRF) recorded during gait initiation. Three
      PC scores were chosen by the scree test for each GRF component and all these PC
      scores were used for calculating a standard distance between healthy controls and
      PD subjects. The Friedman test showed a significant difference in standard
      distance among conditions (P=0.004), with the post-hoc test recognizing
      differences among P1 conditions and P2 medication-on condition. The eigenvector
      loading factors pointed to major differences between PD conditions surrounding
      the maximum amplitude of vertical and anterior-posterior GRF. For the studied
      sample, all distances increased in the follow-up evaluation (P2) with and without
      medications, indicating a worsening in gait initiation after seven years.

PMID- 22154115
TI  - The improvement of walking speed after cardiac rehabilitation is associated with
      the reduction in the metabolic cost of walking in older persons.
AB  - BACKGROUND: To walk a given distance older persons consume more metabolic energy
      than younger adults across all speeds. As physical activity interventions improve
      a variety of physical performance measures in older persons, including walking
      speed, in this study we hypothesized that the improvement of walking speed might
      be associated with the reduction of the metabolic cost of walking and we tested
      our hypothesis in a selected sample of older patients receiving cardiac
      rehabilitation. METHODS: In 120 patients (88 men and 32 women, mean age 74.1
      years+/-SD 5.0) we assessed energy expenditure during the 6-min Walk Test (6mWT)
      before and after the rehabilitation using a portable system for direct
      calorimetry. RESULTS: On the 6mWT performed after the rehabilitation patients
      significantly increased total energy expenditure (28.0 kcal+/-SD 8.3 vs. 25.7
      kcal+/-SD 7.6, p<0.001), the distance walked (398 m+/-SD 93 vs. 343 m+/-SD 95,
      p<0.001) and, consequently, walking speed (1.11 m/s+/-SD 0.26 vs. 0.95m/s+/-SD
      0.26, p<0.001) while the metabolic cost of walking, i.e. the amount of energy
      used to move a body mass of 1 kg for a distance of 1m, was significantly reduced
      (1.00 cal/kg/m+/-SD 0.19 vs. 1.11 cal/kg/m+/-SD 0.32, p<0.001). CONCLUSIONS: In
      older patients receiving cardiac rehabilitation the improvement of walking speed
      is associated with the improvement of walking economy. This might be a
      contributory factor to the favourable effects of physical activity interventions
      on physical performance measures.

PMID- 22154116
TI  - Routine cardiac evaluation in patients with early-stage breast cancer before
      adjuvant chemotherapy.
AB  - INTRODUCTION: This population-based study of women diagnosed with early-stage
      breast cancer aimed to (i) determine the current utilization pattern of
      multigated acquisition (MUGA) scans before adjuvant chemotherapy (AdjC)
      treatment, and (ii) examine the impact of MUGA scan results on AdjC decision
      making. METHODS: All women who underwent curative-intent surgery for stage I-III
      breast cancer between October 2005 and September 2006 in Nova Scotia, Canada,
      were identified through the provincial cancer registry. A retrospective chart
      review was performed to abstract all relevant clinical-pathologic variables,
      including baseline cardiac risk factors. The association between MUGA scan
      utilization and clinical-pathologic variables, as well as receipt and type of
      AdjC, was examined through univariate and multivariate analyses. RESULTS: The
      study included 593 women, of whom 238 (40%) received AdjC (94% anthracycline vs.
      6% nonanthracycline) and 198 (33%) underwent baseline MUGA scans. Of those
      received AdjC, 80% underwent MUGA scans. MUGA scan utilization was associated
      with AdjC treatment (yes vs. no; P < .0001), Her-2/neu status (positive vs.
      negative vs. not tested; P < .0001), and AdjC regimen (anthracycline vs.
      nonanthracycline; P < .0001). Abnormal MUGA results were observed in 5 (2.5%) of
      198; all were smokers, and 4 were >65 years of age. In the 1 patient <50 years
      old, subsequent echocardiograms indicated normal cardiac function. CONCLUSIONS:
      Routine baseline MUGA scans before AdjC were abnormal and changed the AdjC
      treatment decision in only 2.5% and 2.0% of patients, respectively. Routine MUGA
      scans before anthracycline-based AdjC without trastuzumab, however, did not
      influence AdjC decisions for younger patients <65 years of age without underlying
      cardiac risk factors.

PMID- 22154117
TI  - Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first
      line treatment of patients with metastatic breast cancer.
AB  - BACKGROUND: Capecitabine, a tumor-activated oral fluoropyrimidine, and albumin
      bound paclitaxel (ab-paclitaxel) have substantial single-agent activity in
      patients with metastatic breast cancer (MBC). Taxane and antimetabolite doublets
      have improved efficacy compared with single agents. This phase II open-label
      trial was designed to test the safety and efficacy of capecitabine and ab
      paclitaxel in previously untreated MBC. PATIENTS AND METHODS: Patients received
      capecitabine (825 mg/m(2) orally twice daily, approximately 12 hours apart, on
      days 1 to 15) and ab-paclitaxel (125 mg/m(2) intravenously on days 1 and 8 of
      each cycle with no premedication) every 3 weeks. The primary endpoint was overall
      objective response rate (ORR), with evaluation performed after every 2 cycles.
      Entry criteria included measurable MBC, human epidermal growth factor receptor 2
      (HER2) negativity, Eastern Cooperative Oncology Group (ECOG) performance status 0
      2, no previous chemotherapy for metastatic disease, and > 6 months since adjuvant
      fluoropyrimidine or paclitaxel treatment. RESULTS: Fifty patients received at
      least 1 dose of study drug, with 46 patients evaluable for efficacy evaluation.
      Three hundred seventy-four cycles of therapy were delivered. Eighty percent of
      patients completed 8 cycles. The ORR was 61% (complete response [CR], 4%; partial
      response [PR], 57%), and 7 patients had sustained (>= 24 weeks) stable disease
      for a clinical benefit rate of 76.1%. The median progression-free survival (PFS)
      was 10.6 months, and the median overall survival was 19.9 months. The most common
      adverse events (AEs) that were >= grade 3 were pain, hand-foot syndrome, and
      neutropenia. CONCLUSION: The combination of weekly ab-paclitaxel plus daily
      capecitabine orally at these doses and scheduling was well tolerated and showed
      substantial efficacy.

PMID- 22154118
TI  - Randomized phase II study of primary systemic chemotherapy and trastuzumab for
      operable HER2 positive breast cancer.
AB  - BACKGROUND: In primary systemic therapy in patients with human epidermal growth
      factor receptor 2 positive (HER2(+)) breast cancer, improvements in pathologic
      complete response (pCR) rate have been achieved by administering trastuzumab.
      PATIENTS AND METHODS: Patients with stage II or IIIA HER2(+) operable breast
      cancer were randomly assigned to receive four 3-weekly cycles of FEC (5
      fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2))
      followed by 4 cycles of 3-weekly trastuzumab (8 mg/kg week 1 and then 6 mg/kg)
      with either 12 weekly doses of paclitaxel 80 mg/m(2) (FEC-PH) or 4 cycles of 3
      weekly docetaxel 75 mg/m(2) (FEC-DH). RESULTS: Between March 2007 and June 2008,
      102 patients were enrolled. Forty-nine patients receiving FEC-PH and 47 receiving
      FEC-DH were assessable for efficacy and safety. Eighty-four patients completed
      treatment and underwent surgery. There was no significant difference in the pCR
      rate between the 2 groups (46.9% [95% CI, 33.7%-60.6%] with FEC-PH vs. 42.6% [95%
      CI, 29.5%-56.8%] with FEC-DH; P = .67). Analysis by hormone receptor (HR) status
      showed pCR rates of 54.2% (32/59) in HR(-) tumors and 29.7% (11/37) in HR(+)
      tumors (P = .02). Among HR(-) tumors, the pCR rates were 65.4% and 45.5% in
      patients treated with FEC-PH and FEC-DH, respectively (P = .13). CONCLUSIONS:
      There was no significant difference in pCR rate between FEC-PH and FEC-DH. Both
      regimens achieved higher pCR rates in HR(-) than HR(+) breast cancer, and there
      was a trend toward higher pCR in HR(-) tumors with FEC-PH compared with FEC-DH.
      Further investigation is warranted to explore the relationship between efficacy
      and HR status.

PMID- 22154119
TI  - [Validation of two software applications for detecting possible pharmacological
      interactions].

PMID- 22154120
TI  - Spent coffee-based activated carbon: specific surface features and their
      importance for H2S separation process.
AB  - Activated carbons were prepared from spent ground coffee. Zinc chloride was used
      as an activation agent. The obtained materials were used as a media for
      separation of hydrogen sulfide from air at ambient conditions. The materials were
      characterized using adsorption of nitrogen, elemental analysis, SEM, FTIR, and
      thermal analysis. Surface features of the carbons depend on the amount of an
      activation agent used. Even though the residual inorganic matter takes part in
      the H(2)S retention via salt formation, the porous surface of carbons governs the
      separation process. The chemical activation method chosen resulted in formation
      of large volume of pores with sizes between 10 and 30A, optimal for water and
      hydrogen sulfide adsorption. Even though the activation process can be
      optimized/changed, the presence of nitrogen in the precursor (caffeine) is a
      significant asset of that specific organic waste. Nitrogen functional groups play
      a catalytic role in hydrogen sulfide oxidation.

PMID- 22154121
TI  - Influence of inlet concentration and light intensity on the photocatalytic
      oxidation of nitrogen(II) oxide at the surface of Aeroxide(r) TiO2 P25.
AB  - Air pollution by nitrogen oxides represents a serious environmental problem in
      urban areas where numerous sources of these pollutants are concentrated. One
      approach to reduce the concentration of these air pollutants is the light-induced
      oxidation in the presence of molecular oxygen and a photocatalytically active
      building material, e.g., paints, roof tiles, or pavement stones. Herein, results
      of an investigation concerning the photocatalytic oxidation of nitrogen(II) oxide
      (NO) in the presence of molecular oxygen and UV(A) irradiated TiO(2) powder are
      presented. The standard operating procedure described in ISO 22197-1 which was
      developed to characterize the photocatalytic activity of air-cleaning products
      was successfully applied to determine the photocatalytic activity of a bare
      TiO(2) powder. The experimental data reveal that at the light intensity
      stipulated by the operation procedure the amount of NO removed from the gas phase
      by photocatalytic oxidation is strongly affected by small changes of this light
      intensity as well as of the NO concentration in the gas stream in the
      photoreactor. Therefore, these parameters have to be controlled very carefully.
      Based upon the experimental data obtained in this study a rate law for the
      photocatalytic NO oxidation inside the photoreactor is derived.

PMID- 22154122
TI  - Batch and continuous biodegradation of three model naphthenic acids in a
      circulating packed-bed bioreactor.
AB  - Generation of process waters contaminated by naphthenic acids is a serious
      environmental concern associated with processing of the oil sands. This together
      with the necessity for sustainable use of water highlights the need for
      development of effective technologies such as bioremediation for treatment of
      these contaminated waters. In this work, a circulating packed bed bioreactor and
      a culture developed in our laboratory were used to study batch and continuous
      biodegradation of trans-4-methyl-cyclohexane carboxylic acid (trans-4MCHCA), a
      mixture of cis- and trans-4-methyl-cyclohexane acetic acid (4-MCHAA), and mixture
      of these three naphthenic acids. Experimental results revealed that the
      biodegradability of the naphthenic acids was influenced by both carbon number and
      the spatial arrangement of the alkyl side branch. The maximum biodegradation rate
      of trans-4MCHCA observed during the continuous operation (209 mg/Lh at a
      residence time of 0.15 h) was significantly higher than those reported for CSTR
      and packed-bed bioreactors. The biodegradation rates of cis- and trans-4-MCHAA
      were much lower than trans-4MCHCA, with the maximum biodegradation rates
      determined for the two isomers being 4.2 and 7.8 mg/Lh, respectively (residence
      time: 3.3 h).

PMID- 22154123
TI  - A meta-analysis of the cross-cultural psychometric properties of the Social
      Phobia and Anxiety Inventory for Children (SPAI-C).
AB  - Several studies have found that the Social Phobia and Anxiety Inventory for
      Children (SPAI-C), an empirically derived self-report instrument to assess DSM-IV
      social phobia in childhood and adolescence, has good psychometric properties.
      While these findings were replicated across different cultures, the overall
      strength of the psychometric properties of the SPAI-C remains unknown. We
      assessed the validity of the SPAI-C by meta-analytic techniques across studies
      collected from PubMed, PsycInfo and Eric databases, conducted in different
      countries, among subjects of different age, and sex. A total of 21 articles were
      retained, predominantly from Europe and North America. We found that the
      psychometric properties based on Cronbach alpha, mean score differences between
      sexes, and construct validity, were robust for the SPAI-C scale. Girls scored
      significantly higher than boys, and geographical differences played a moderating
      effect on sex-related score differences. These results further support the SPAI-C
      as an instrument to identify Social Phobia in youth.

PMID- 22154125
TI  - Lymphangiogenesis in COPD: another link in the pathogenesis of the disease.
AB  - BACKGROUND: New lymphatic vessels are associated with tissue injury and repair.
      Recent studies have shown increased lymphatic follicles formation in the lungs of
      COPD patients. We hypothesized that lymphatic vascular remodeling could be part
      of COPD pathogenesis. AIM: To investigate the lymphangiogenetic process in COPD
      we measured the lymphatic microvessel density (LMVD), the lymphatic invasion
      (L.I), and their correlation with clinical and laboratory parameters. METHODS:
      Lung tissue from 20 COPD patients and 20 non-COPD smokers was
      immunohistochemically stained for D2-40 (lymphatic endothelial cell marker), and
      LYVE-1 (lymphatic endothelial hyaluronan receptor 1). Both groups had similar age
      and smoking history. RESULTS: D2-40 and LYVE-1 were expressed in all specimens.
      Lymphatic invasion was presented only in COPD specimens. Lymphatic microvessel
      density (LMVD) as revealed by D2-40 and LYVE-1 markers was statistically
      significantly higher in COPD patients when compared with non-COPD smokers. Both
      markers (D2-40, LYVE-1) were correlated with FEV1 (% pred) (R(2) = 0.415, R(2) =
      0.605, respectively). CONCLUSIONS: We report for the first time high lymphatic
      microvessel density and lymphatic invasion in COPD patients, related to the
      degree of airway obstruction. Our findings could provide novel insights in the
      pathogenesis of the disease.

PMID- 22154124
TI  - Centromeric chromatin and the pathway that drives its propagation.
AB  - The centromere is the locus that directs chromosomal inheritance at cell
      division. While centromeres in diverse eukaryotes are commonly found at sites of
      repetitive DNA, their location is epigenetically specified. The histone H3
      variant CENP-A is the prime candidate for epigenetically marking the centromere,
      and recent work has uncovered several additional proteins that play key roles in
      centromere assembly and maintenance. We describe advances in the identification
      and characterization of proteins that form the centromere, and focus on recent
      findings that have advanced our understanding of the assembly of functional
      centromeric chromatin. This article is part of a Special Issue entitled: Histone
      chaperones and chromatin assembly.

PMID- 22154126
TI  - A better response in exercise capacity after pulmonary rehabilitation in more
      severe COPD patients.
AB  - PURPOSE: Pulmonary rehabilitation (PR) has positive effects on exercise capacity
      in Chronic Obstructive Pulmonary Disease (COPD). However, not all COPD patients
      benefit from PR to the same extent. We investigated whether there is a patient
      profile, which is associated with the improvement in endurance exercise capacity.
      METHODS: In this observational study, we included 102 COPD patients who followed
      PR (age 60 +/- 10 (mean +/- SD) years, FEV(1)%predicted 44 +/- 16%, 54 men). Lung
      function, maximal incremental cycle testing (Wpeak, VO(2)peak, Deltalactate),
      quadriceps force and incremental and endurance shuttle walk test (ISWT/ESWT) were
      performed at the start of PR. The ESWT was repeated after 7 weeks of PR. RESULTS:
      Mean change in ESWT (DeltaESWT) was 100 +/- 154%. Four variables showed a
      statistically significant negative correlation with DeltaESWT: FEV(1)%pred. (rho
      = -0.20), Wpeak (rho = -0.24), Deltalactate (rho = -0.33) and incremental shuttle
      walk test (ISWT) (rho = -0.31). A cluster analysis identified two patient
      profiles: A profile with high DeltaESWT, TLC and RV and low FEV(1), VO(2)peak,
      quadriceps force, Deltalactate, HR(peak)%pred. and ISWT distance and a profile
      with low DeltaESWT, TLC and RV and high FEV(1), VO(2)peak, quadriceps force,
      Deltalactate, HR(peak)%pred. and ISWT distance. CONCLUSIONS: Single variables
      from lung function or exercise testing at baseline have limited predictive value
      for response to exercise training. However, patients with worse disease status
      (i.e. a combination of lower FEV(1), more hyperinflation, lower exercise capacity
      and worse quadriceps force) improve more in endurance exercise capacity.

PMID- 22154128
TI  - Prediction model for early percutaneous endoscopic gastrostomy (PEG) in head and
      neck cancer treatment.
AB  - Head and neck cancer patients are prone to nutritional problems, partly due to
      the location and size of the disease, due to significant comorbidity and also
      often therapeutic intervention. Excessive weight loss after surgery reduces
      further the patients' physical resistibility and increases the complication rate
      for adjuvant radiation and or chemotherapy. Possible effective interventions are
      dietary counseling, nutritional supplements or drug interventions. Aim of our
      research was to reveal reliable clinical predictive parameters, which calculate
      risks as the reduced nutritional state against the possible complications of PEG
      insertion and finally define an algorithm for pre-therapeutic PEG insertion to
      optimize the general treatment conditions by sufficient nutrition. We explored
      the data of 152 patients in a time period from 2005 to 2010 considering age,
      gender, body mass index, staging, size and localization of the tumor or need for
      a neck dissection. The decisive predictive parameters are: body mass index, size
      and localization of tumor, lymph node affection, resection of the root of the
      tongue or the oropharynx region and performance of a neck dissection. In this
      retrospective study we established a prediction model that allows a substantiated
      evaluation of post-therapeutic dysphagia considering relevant clinical features
      as well as the specific surgical therapy. From this assessment derives the
      indication of a safe pre-therapeutic application of a percutaneous endoscopic
      gastrostomy (PEG).

PMID- 22154127
TI  - Psychological functioning of caregivers for head and neck cancer patients.
AB  - Patients with head and neck squamous cell carcinoma (HNSCC) often require
      assistance from family caregivers during the treatment and post-treatment period.
      This review article sought to summarize current findings regarding the
      psychological health of HNSCC caregivers, including factors that may be
      associated with poorer psychological health. Online databases (PUBMED, MEDLINE
      and PSYCINFO) were searched for papers published in English through September
      2010 reporting on the psychological health of caregivers of HNSCC patients.
      Eleven papers were identified. Caregivers experience poorer psychological health,
      including higher levels of anxious symptoms, compared to patients and to the
      general population. Fear of patient cancer recurrence is evident among caregivers
      and is associated with poorer psychological health outcomes. The 6-month interval
      following diagnosis is a significant time of stress for caregivers. Greater
      perceived social support may yield positive benefits for the psychological health
      of caregivers. To date, there have been relatively few reports on the
      psychological health of caregivers of HNSCC patients. Well designed, prospective,
      longitudinal studies are needed to enhance our understanding of how caregiver
      psychological health may vary over the cancer trajectory and to identify
      strategies for improving caregiver outcomes.

PMID- 22154129
TI  - Accuracy of MRI in prediction of tumour thickness and nodal stage in oral
      squamous cell carcinoma.
AB  - We aim to compare radiological with histological tumour thickness (RTT with HTT)
      for oral squamous cell carcinoma (OSCC), and the ability of both to predict
      cervical metastasis. The MRI images and histopathology reports of 102 consecutive
      OSCC cases were compared and the relationship between RTT and HTT, calculated as
      a "shrinkage factor" by the gradient of the best fitting regression line. Most
      (69%) tumours appeared thicker on MRI than was revealed by histopathology.
      Shrinkage factor was 0.70 (interquartile range 0.63-0.77, correlation co
      efficient 0.63) for all cases, 0.87 (IQR 0.80-0.95, CC 0.88) for tongue and 0.65
      (IQR 0.49-0.82, CC 0.45) for floor of mouth sub-sites. RTT did not correlate well
      with the presence of nodal metastases in any sub-site, i.e. there was no
      clinically applicable cut-off value of RTT to determine the prescription of
      elective neck dissection. Although RTT has some predictable relationship with
      HTT, this varies between sub-sites with tongue the most accurately predicted
      shrinkage using axial MRI. It is not possible from either the MRI staging of neck
      or tumour thickness to safely determine the need for neck dissection in OSCC. It
      is necessary to re-evaluate the benefit of MRI as a staging investigation
      (particularly for early stage OSCC) and further explore the contribution of
      molecular biomarkers and ultrasound.

PMID- 22154130
TI  - Exploring the theory of planned behavior to explain sugar-sweetened beverage
      consumption.
AB  - OBJECTIVE: To describe sugar-sweetened beverage (SSB) consumption and to
      establish psychometric properties and utility of a Theory of Planned Behavior
      (TPB) instrument for SSB consumption. METHODS: This cross-sectional survey
      included 119 southwest Virginia participants. Most of the respondents were female
      (66%), white (89%), and had at least a high school education (79%), and their
      average age was 41.4 +/- 13.5 years. A validated beverage questionnaire was used
      to measure SSB. Eleven TPB constructs were assessed with a 56-item instrument.
      Analyses included descriptive statistics, 1-way ANOVA, Cronbach alpha, and
      multiple regression. RESULTS: Sugar-sweetened beverage intake averaged 457 +/-
      430 kcal/d. The TPB model provided a moderate explanation of SSB intake (R(2) =
      0.38; F = 13.10, P < .01). Behavioral intentions had the strongest relationships
      with SSB consumption, followed by attitudes, perceived behavioral control, and
      subjective norms. The 6 belief constructs did not predict significant variance in
      the models. CONCLUSIONS AND IMPLICATIONS: Future efforts to comprehensively
      develop and implement interventions guided by the TPB hold promise for reducing
      SSB intake.

PMID- 22154131
TI  - Family ties to health program: a randomized intervention to improve vegetable
      intake in children.
AB  - OBJECTIVE: Evaluate a home-based intervention targeted toward parents to improve
      vegetable intake in preschool-aged children. METHODS: Four-month feasibility
      study of home-based intervention consisting of 4 tailored newsletters and 2
      motivational phone calls compared to control; 4 children's books for the control
      group; and measured pre and post parent-reported physical and social home
      environment and child vegetable intake in 22 intervention and 21 control homes
      with a child 2-5 years old assessed with linear regression of group predicting
      home environment and diet characteristics post-intervention, adjusting for
      baseline (P < .05 significant). RESULTS: Intervention increased availability of
      vegetables (+1.5 +/- 2.5 vegetable types vs -0.3 +/- 2.7 vegetable types, P =
      .02), offering fruits and vegetables for snacks (+0.95 +/- 1.5 d/wk vs -0.05 +/-
      1.9 d/wk, P = .04), and self-efficacy (+2.4 +/- 4.1 vs -0.3 +/- 2.0, P = .02).
      CONCLUSIONS AND IMPLICATIONS: The data suggest potential for home-based
      interventions to alter parent behaviors such as feeding practices and the home
      physical environment, which may be steps toward increasing vegetable intake in
      children.

PMID- 22154132
TI  - The influence of cartoon character advertising on fruit and vegetable preferences
      of 9- to 11-year-old children.
AB  - OBJECTIVE: The aim of the present study is to determine the influence of cartoon
      characters in preferences of fruit and vegetables among children. METHODS: A 10
      item survey was used in this cross-sectional study to determine the factors that
      influence a child's likelihood of eating fruits and vegetables. Seven factors
      influencing consumption of fruits and vegetables were rank ordered by 218 third-
      and fourth-grade students. RESULTS: Results indicated that the child was more
      likely to eat fruits or vegetables if they tasted good, followed by whether they
      were nutritious. Presence of a cartoon character on the label ranked 6 of 7. Sex
      does not affect the rank order of factors that influence intake of fruits or
      vegetables. CONCLUSIONS AND IMPLICATIONS: Future interventions aimed at
      increasing consumption of fruits and vegetables should take into consideration
      such factors that influence intake.

PMID- 22154133
TI  - Ascorbic acid treatment, similarly to fluoxetine, reverses depressive-like
      behavior and brain oxidative damage induced by chronic unpredictable stress.
AB  - Reactive oxygen species (ROS) have been shown to play a role in the
      pathophysiology of depression. Taking into account that experimental chronic
      unpredictable stress (CUS) induces depressive-like behavior and that ascorbic
      acid has antidepressant-like effect in animals, the objective of this study was
      to investigate the influence of ascorbic acid on depressive-like behavior induced
      by CUS paradigm, serum corticosterone levels and markers of oxidative stress in
      cerebral cortex and hippocampus of mice. Animals were submitted to CUS procedure
      during 14 days. From the 8th to the 14th day mice received ascorbic acid (10
      mg/kg) or fluoxetine (10 mg/kg, conventional antidepressant, positive control)
      once a day by oral route. On 15th day behavioral and biochemical parameters were
      analyzed. CUS exposure caused a depressive-like behavior evidenced by the
      increased immobility time in the tail suspension test and decreased time in which
      mice spent grooming in the splash test. Depressive-like behavior induced by CUS
      was accompanied by a significant increased lipid peroxidation (cerebral cortex
      and hippocampus), decreased catalase (CAT) (cerebral cortex and hippocampus) and
      glutathione reductase (GR) (hippocampus) activities and reduced levels of
      glutathione (cerebral cortex). Repeated ascorbic acid or fluoxetine
      administration significantly reversed CUS-induced depressive-like behavior and
      oxidative damage. No alteration was observed in locomotor activity,
      corticosterone levels and glutathione peroxidase (GPx) activity. These findings
      indicate a rapid and robust effect of ascorbic acid in reversing behavioral and
      biochemical alterations induced by CUS in mice, suggesting that this vitamin may
      be an alternative approach for the management of depressive symptoms.

PMID- 22154134
TI  - Support for a novel five-factor model of posttraumatic stress symptoms in three
      independent samples of Iraq/Afghanistan veterans: a confirmatory factor analytic
      study.
AB  - BACKGROUND: A large body of confirmatory factor analytic studies of posttraumatic
      stress disorder (PTSD) symptoms has demonstrated the superiority of 4-factor
      dysphoria and emotional numbing models over the DSM-IV model. Recently, a novel 5
      factor model, which separates the DSM-IV hyperarousal symptom cluster into
      distinct dysphoric and anxious arousal clusters, has been identified. However,
      little research has evaluated the best-fitting representation of PTSD symptoms in
      veterans of the Iraq and Afghanistan wars. METHODS: Confirmatory factor analyses
      were used to examine the factor structure of the PTSD Checklist in three
      independent samples of Iraq/Afghanistan veterans, including two community samples
      and a treatment-seeking sample. RESULTS: In all three samples, a novel model with
      five correlated factors reflecting symptoms of re-experiencing, avoidance,
      emotional numbing, dysphoric arousal, and anxious arousal provided a
      significantly better representation of PTSD symptoms than the DSM-IV, dysphoria,
      and numbing models. This model also showed evidence of "excellent fit" in the
      community samples according to empirically-defined benchmarks. CONCLUSIONS: These
      findings suggest that PTSD symptomatology in both community and treatment-seeking
      Iraq/Afghanistan veterans may be best represented by a 5-factor model that
      separates the DSM-IV PTSD hyperarousal symptom cluster into distinct dysphoric
      arousal and anxious arousal clusters.

PMID- 22154135
TI  - Racial disparities in outcomes after appendectomy for acute appendicitis.
AB  - BACKGROUND: Although black patients with acute appendicitis have been shown to be
      less likely than whites to undergo laparoscopic appendectomy, it is unknown
      whether they suffer increased complications after surgical management of acute
      appendicitis. METHODS: A retrospective analysis of all patients undergoing
      appendectomy for acute appendicitis from 2005 through 2009, using the National
      Surgical Quality Improvement Program database, was conducted. Rates of serious
      and overall morbidity were compared between blacks and whites, with adjustment
      for preoperative risk factors, the severity of appendicitis, and surgical
      approach. RESULTS: Blacks were more likely than whites to suffer serious
      postoperative complications (4.8% vs 3.3%; adjusted odds ratio vs whites, 1.39;
      95% confidence interval, 1.16-1.67; P = .0002) or any complication (8.4% vs 6.0%;
      adjusted odds ratio vs whites, 1.31; 95% confidence interval, 1.14-1.50; P =
      .0007). CONCLUSIONS: Racial disparities in postoperative outcomes exist for even
      a procedure as ubiquitous as appendectomy. More research is needed to determine
      the underlying reasons for these disparities.

PMID- 22154136
TI  - Feasibility study of two-stage hepatectomy for bilobar liver metastases.
AB  - BACKGROUND: The aim of this study was to analyze the feasibility and early
      outcomes of 2-stage liver resection for bilobar metastases. METHODS: Data from 39
      consecutive patients undergoing 2-stage hepatectomy between 2004 and 2010 were
      prospectively collected. RESULTS: The median age was 59 years (range, 33-79
      years), and the ratio of men to women was 1.8:1. Metastases were colorectal
      carcinoma (n = 33), neuroendocrine tumors (n = 3), gastrointestinal stromal tumor
      (n = 1), ocular melanoma (n = 1), and salivary gland carcinoma (n = 1).
      Perioperative chemotherapy was given to 32 patients (82%). Twenty-nine patients
      (74%) underwent portal venous embolization. Radiofrequency ablation was used in 8
      patients (21%). Twenty-seven patients (69%) successfully completed clearance. For
      the 1st and 2nd stages, the median lengths of stay were 11 days (range, 6-53
      days) and 13 days (range, 6-44 days), and morbidity rates were 23% and 56%. Liver
      insufficiency occurred in 2 (5%) and 6 (22%) patients. Overall mortality was
      2.6%. For colorectal metastases, median survival in successes versus failures was
      24 versus 10 months (P = .03), and 3-year survival was 30% versus 0%.
      CONCLUSIONS: Two-stage hepatectomy is feasible, with 69% of patients achieving
      clearance with low mortality. Morbidity is significant, particularly transient
      hepatic insufficiency.

PMID- 22154137
TI  - Ciliary motility: the components and cytoplasmic preassembly mechanisms of the
      axonemal dyneins.
AB  - Motile cilia and flagella are organelles, which function in cell motility and in
      the transport of fluids over the surface of cells. Motility defects often result
      in a rare human disease, primary ciliary dyskinesia (PCD). Cell motility depends
      on axonemal dynein, a molecular motor that drives the beating of cilia and
      flagella. The dyneins are composed of multiple subunits, which are thought to be
      preassembled in the cytoplasm before they are transported into cilia and
      flagella. Axonemal dyneins have been extensively studied in Chlamydomonas. In
      addition, analyses of human PCDs over the past decade, together with studies in
      other model animals, have identified the conserved components required for dynein
      assembly. Recently also, the first cytoplasmic component of dynein assembly,
      kintoun (ktu), was elucidated through the analysis of a medaka mutant in
      combination with human genetics and cell biology and biochemical studies of
      Chlamydomonas. The components of dynein and the proteins involved in its
      cytoplasmic assembly process are discussed.

PMID- 22154138
TI  - Cilia and Hedgehog: when and how was their marriage solemnized?
AB  - Primary cilia are essential for Hedgehog (Hh) signaling in mammals, and this
      requirement appears to be conserved in other vertebrates as well. Here, I review
      recent work that has scrutinized the evolution of the link between the Hh pathway
      and cilia, discuss what we have learnt from these studies and speculate on how
      this fascinating problem can be further explored.

PMID- 22154139
TI  - [Other actors in the oocyte and follicular growth: the role of microRNAs in the
      cumulus-oocyte dialog].
AB  - The good folliculogenesis evolution is fundamental for the obtaining of a
      competent oocyte, able to lead to pregnancy, once fertilized. During the
      follicular development, the oocyte is in close contact with surrounding cumulus
      cells (CCs) to form a cumulus-oocyte complex. The bidirectional exchange between
      oocyte and contiguous CCs via gap junction communications and paracrine signaling
      is important for oocyte competence and CCs development. These reciprocal
      regulations are controlled by some key genes. Recently, it has been demonstrated
      that these genes are themselves regulated by short RNAs fragments (approximately
      22 nucleotides), called microRNAs. The identification and the quantification in
      the CCs of the microRNAs regulating these genes could promote the development of
      non invasive tests in order to assess the oocyte quality and its ability to
      provide embryo with a high implantation potential. This approach could be
      decisive in the embryo selection to transfer and could avoid the risk of multiple
      pregnancies by the replacement of a single embryo.

PMID- 22154140
TI  - [Clinical and ultrasonographic factors affecting successful medical treatment of
      early pregnancy failure].
AB  - OBJECTIVES: To assess clinical and echocardiographic factors impacting the
      effectiveness of misoprostol in early pregnancy failure. PATIENTS AND METHODS: An
      observational study was carried out within the gynaecological emergency service
      from 01/06/2000 to 15/05/2010. Patients had pregnancy failure in the first 12
      weeks at ultrasonic examination. The patient received 4 misoprostol tablets (800
      MUg) intravaginally with clinical and ultrasound examination 24 hours later. The
      treatment was considered effective if the endometrial thickness was lower than 15
      mm by ultrasound examination and absence of secondary endo-uterine aspiration. If
      the treatment was considered as a failure, an endo-uterine aspiration was carried
      out. Variables studied were clinical (patient age, date of the last menstrual
      period, gravidity, parity, history of miscarriage, endouterine aspiration,
      ectopic pregnancy, vaginal delivery, caesarean section) and ultrasound-based
      (presence or absence of an embryo, CRL, gestational sac diameter). RESULTS: Five
      hundred and one patients were included. The success rate was 336/501 (67.1%).
      After univariate analysis, the averages of parity (P=0.048) and caesarean section
      (P=0.002) were significantly higher in failure cases. The history of one or more
      caesarean section was a significant risk factor for failure (P=0.001). There was
      no significant difference for the other criteria. In multivariate analysis, the
      average number of caesarean sections (P=0.003) and the history of one or more
      caesarean section remained significant (P=0.002). DISCUSSION AND CONCLUSION: The
      ultrasound criteria and gestational age do not impact the effectiveness of
      misoprostol in the treatment of early pregnancy failure. The history of one or
      more caesarean section (s) significantly decreased the success rate. It has to be
      confirmed by other studies. This new data can be an aid to decision-making for
      the patient and the physician in case of early pregnancy failure.

PMID- 22154141
TI  - A contemporary evaluation of the acrasids (Acrasidae, Heterolobosea, Excavata).
AB  - Sorocarpic protists are organisms that individually aggregate and work together
      to form a fungus-like fruiting body (sorocarp). The amoeboid forms are often
      colloquially referred to as "cellular slime molds" or "acrasids". We argue the
      latter term should be used only to refer to members of Acrasidae in
      Heterolobosea. Here we study the diversity of two Acrasidae genera, Acrasis and
      the closely similar Pocheina, using a combination of morphological
      characteristics and small subunit rRNA gene sequences. A total of eight isolates
      of Acrasis and an example of Pocheina were examined. Acrasis/Pocheina form a well
      supported monophyletic group that is the highly supported sister to a clade
      containing Allovahlkampfia and several other amoebae. Four molecular lineages of
      Acrasis were resolved, each of which is characterized by a distinctive fruiting
      body morphology. Each lineage represents a species, two of which are novel,
      Acrasis kona n. sp. and Acrasis takarsan n. sp. An isolate identified as Pocheina
      rosea is nested within the clade containing isolates of the taxon Acrasis rosea,
      into which P. rosea is tentatively subsumed. One member of the tightly knit
      allovahlkampfid clade was induced to form a simple sorocarp, leading us to
      include this clade in Acrasidae.

PMID- 22154142
TI  - Acute toxicity of manganese in goldfish Carassius auratus is associated with
      oxidative stress and organ specific antioxidant responses.
AB  - Manganese is a relatively common, yet poorly studied element in freshwater
      ecosystems, where it can be significantly bioconcentrated. The knowledge about
      the mechanisms of Mn toxicity on fish health is still limited. The aim of the
      present study was to assess the potential induction of oxidative stress and the
      antioxidant response after a 96 h waterborne Mn-exposure (at 0.1 and 1mM) in
      gill, kidney, liver and brain of goldfish (Carassius auratus). Mn 1mM induced an
      increase of lipid hydroperoxides, superoxide dismutase (SOD) and glutathione
      peroxidase (GPx) activities in all tissues with the exception of SOD inhibition
      in the brain. Particular response of catalase (CAT) was indicated-its inhibition
      in the liver and kidney, but activation in the gill. Exposure to Mn 0.1mM
      provoked most prominent changes in the liver and did not change the indexes in
      brain. These results strongly suggest that Mn exposure caused a generalized
      oxidative stress in the fish and revealed an organ specific antioxidant response
      involving a differential modulation of the SOD, CAT and GPx activities.

PMID- 22154143
TI  - Biomarker gene response in male Medaka (Oryzias latipes) chronically exposed to
      silver nanoparticle.
AB  - The chronic toxicity test has been conducted for twenty-eight days to
      characterize the hepatic expression levels of eight stress-related genes after
      exposing Medaka to two doses of silver nitrate or a silver nanoparticle (Ag-NP)
      using real time RT-PCR analysis. This extends our previously published work to
      include three additional biomarkers and three later time points. In comparing
      with the control, the significant induction of MT and GST genes in livers of the
      fish exposed to 1 MUg/l Ag-NPs was observed at various time points during the
      test period. The Orla C3-1 (Medaka) gene was slightly induced only with 1 MUg/l
      Ag-NPs at 7-day exposure while the suppression of p53 and HSP70 was recorded in
      all exposures at the end of the test. The gene encoding transferrin was repressed
      at day 21 by both silver types and at every exposure dosage. These results
      revealed that the Ag-NPs increase metal detoxification, oxidative and
      inflammatory stress, and finally stimulate immune responses in Medaka. The
      conspicuous induction of choriogenin L and vitellogenin 1 in male fish exposed to
      Ag-NPs, especially at 7- and 21-day, compared with the exposures of AgNO(3) or
      control was the first attempt to examine estrogenic effects of Ag-NPs.

PMID- 22154144
TI  - Application of electrolysis for detoxification of an antineoplastic in urine.
AB  - Antineoplastics in excreta from patients have been considered to be one of the
      origins of cytotoxic, carcinogenic, teratogenic, and mutagenic contaminants in
      surface water. Recent studies have demonstrated that antineoplastics in clinical
      wastewater can be detoxified by electrolysis. In this study, to develop a method
      for the detoxification of antineoplastics in excreta, methotrexate solution in
      the presence of human urine was electrolyzed and evaluated. We found that urine
      inhibits detoxification by electrolysis; however, this inhibition decreased by
      diluting urine. In urine samples, the concentrations of active chlorine generated
      by anodic oxidation from 0.9% NaCl solution for inactivation of antineoplastics
      increased in dilution-dependent and time-dependent manner. These results indicate
      that electrolysis with platinum-based iridium oxide composite electrode is a
      possible method for the detoxification of a certain antineoplastic in urine.

PMID- 22154145
TI  - Effects of uranium on crayfish Procambarus clarkii mitochondria and antioxidants
      responses after chronic exposure: what have we learned?
AB  - We examined the impacts of Uranium (U) on mitochondria and on the response of
      antioxidants in the gills and the hepatopancreas of crayfish Procambarus clarkii
      after long-term exposure (30 and 60 days) to an environmentally relevant
      concentration (30 MUg U/L). The expression of mitochondrial genes (12s, atp6, and
      cox1), as well as the genes involved in oxidative stress responses (sod(Mn) and
      mt) were evaluated. The activities of antioxidant enzymes (SOD, CAT, GPX and GST)
      were also studied. U accumulation in organs induced changes in genes' expression.
      The evolution of these transcriptional responses and differences between gene
      expression levels at high and low doses of exposure were also discussed. This
      study demonstrated that, after long-term exposure, U caused a decrease in
      antioxidant activities and induced oxidative stress. A possible ROS-mediated U
      cytotoxic mechanism is proposed. Expression levels of the investigated genes can
      possibly be used as a tool to evaluate U toxicity and seem to be more sensitive
      than the enzymatic activities. However a multiple biomarker approach is
      recommended as the perturbed pathways and the mode of action of this pollutant
      are not completely understood.

PMID- 22154146
TI  - Acute toxicity and n-octanol/water partition coefficients of substituted
      thiophenols: determination and QSAR analysis.
AB  - The acute toxicity (-log EC(50)) to Photobacterium phosphoreum and the n
      octanol/water partition coefficient (log K(ow)) of 31 kinds of substituted
      thiophenols were determined at 298.15K. The -log EC(50) values of studied
      chemicals are between 4.26 and 5.89. Their log K(ow) values are between 1.34 and
      4.02. Comparative molecular field (CoMFA) and comparative molecular similarity
      index analysis (CoMSIA) models established were successful in predicting -log
      EC(50) and log K(ow) values of halogenated, methylic, amino and methoxy
      thiophenols. The size of molecule is the main factor influencing the properties.
      No correlation was found between the properties and their structural and
      thermodynamic descriptors from DFT calculation.

PMID- 22154147
TI  - Spontaneous resorption of sequestrated intervertebral disc herniation.
AB  - OBJECTIVE: The aim of this study is to describe six cases with spontaneous
      resorption of sequestrated intervertebral disc herniation observed using magnetic
      resonance imaging. In addition, the possible mechanisms, predictive factors of
      spontaneous disappearance of the sequestrated disc herniation, and the proper
      surgical timing were discussed and reviewed in literature. METHODS: All the
      studied cases experienced acute radicular pain due to sequestrated intervertebral
      disc herniation; they refused surgery and were treated conservatively, and they
      were followed up neurologically and radiologically in the outpatient clinic in
      regular visits. RESULTS: The studied cases included five cases with lumbar disc
      herniation (three at level L4-5 and two at level L5-S1) and one case with
      cervical disc herniation at level C5-6. All patients recovered from their
      radicular pain within 3 to 6 weeks, and it was correlated with resorption of
      their sequestrated intervertebral disc herniation as documented in their follow
      up magnetic resonance imaging at 4 to 9 months. CONCLUSIONS: We found that
      sequestrated disc herniation has potential for regression, which can be clearly
      demonstrated by magnetic resonance imaging, because of having higher water
      content, and therefore, may regress through both dehydration and inflammation
      mediated resorption. We suggest conservative treatment in the initial course of
      the sequestrated type of disc herniation for at least 2 months before
      recommending surgical intervention unless severe neurologic deterioration takes
      place.

PMID- 22154148
TI  - Subdural drainage versus subperiosteal drainage in burr-hole trepanation for
      symptomatic chronic subdural hematomas.
AB  - BACKGROUND: Symptomatic chronic subdural hematoma (scSDH) is one of the most
      frequent diseases in neurosurgical practice, and its incidence is increasing.
      However, treatment modalities are still controversial. OBJECT: The aim of this
      retrospective single-center study is to compare for the first time two surgical
      methods in the treatment of subdural hematoma that have been proven to be
      efficient in previous studies in a direct comparison. METHODS: We analyzed the
      data of 143 scSDHs in 113 patients undergoing surgery for subdural hematoma with
      placement of subperiosteal or subdural drainage after double burr-hole
      trepanation for hematoma evacuation. RESULTS: Overall, there were no
      statistically significant differences regarding general patient characteristics,
      preoperative and postoperative symptoms, postoperative hematoma remnant, rates of
      recurrences, mortality, complications, and outcome at discharge and at 3-month
      follow up between the groups. There was a close to significant tendency of lower
      mortality after placement of subperiosteal drainage system and a tendency towards
      lower rate of recurrent hematoma after placement of subdural drainage system.
      CONCLUSIONS: Our study shows for the first time a direct comparison of two mainly
      used surgical techniques in the treatment of scSDH. Both methods proved to be
      highly effective, and general patient data, complications, outcome and mortality
      of both groups are equal or superior compared with previously published series.
      Because there is a clear tendency to less mortality and fewer serious
      complications, treatment with double burr-hole trepanation, irrigation, and
      placement of subperiosteal drainage is our treatment of choice in patients with
      predictable high risk of complications.

PMID- 22154149
TI  - Management of supratentorial intracerebral hemorrhage-still a controversy?

PMID- 22154150
TI  - Outcome, reoperation, and complications in 99 consecutive children operated for
      tight or fatty filum.
AB  - OBJECTIVE: Recent studies have suggested that retethering in patients operated
      for a tight or fatty filum is higher than previously predicted. In this
      retrospective review, outcome, complications, and risk of reoperation for
      recurrent tethered cord syndrome (TCS) at our own institution were investigated.
      METHODS: The medical records of 100 consecutive children who underwent initial
      division of the filum terminale at Cincinnati Children's Hospital Medical Center
      (November 1995-May 2006) for a tight or fatty filum were reviewed. One patient
      was excluded due to previous spinal surgery at an outside institution. Presenting
      symptoms/signs, magnetic resonance imaging findings, complications, postoperative
      symptoms/signs, and need for reoperation were recorded. Mean follow-up for 97 of
      the 99 patients was 33 months; 80 were followed for 6 months or more and 68 were
      followed for 12 months or more. RESULTS: The most common presenting symptoms were
      bladder and/or bowel dysfunction, followed by gait abnormality, back pain, and
      spasticity. At last follow-up, 85 patients were improved or stable, whereas 12
      patients had at least one symptom or sign that had worsened. Five children
      required a second operation for recurrent TCS. Mean time to reoperation was 58
      months (range 22-73 months). Arachnoid adhesions accounted for the retethering in
      four of five patients. There were a total of 12 complications in 9 patients
      including 5 wound infections, 4 cerebrospinal fluid leaks, 1 pseudomeningocele, 1
      stitch abscess, and 1 transient headache. CONCLUSIONS: Division of a tight or
      fatty filum, in this consecutive series of pediatric patients, resulted in
      improved or stable neurological symptoms in 88% of patients. However, the
      complication and reoperation rate for recurrent TCS were not insignificant.
      Future studies aimed at reducing complications and retethering in this population
      may be warranted.

PMID- 22154151
TI  - A case for further investigating the use of controlled lumbar cerebrospinal fluid
      drainage for the control of intracranial pressure.
AB  - OBJECTIVE: Increased intracranial pressure (ICP) that is refractory to medical
      measures and ventriculostomy placement after severe traumatic brain injury or
      aneurysmal rupture is associated with high mortality. In some recent reports,
      authors have described the use of lumbar cerebrospinal fluid drainage in these
      patients. We report the results of a prospective study involving the use of
      lumbar drainage in 15 patients with elevated ICP that was refractory to medical
      management and ventriculostomy placement. METHODS: A prospective study was
      designed to enroll patients at Loma Linda University Medical Center. Ten patients
      with traumatic brain injury and five patients with ruptured aneurysms were
      enrolled. Medical management included maintaining serum Na >150 mEq/L, mild
      hyperventilation, deep sedation, and maintenance of normothermia. A lumbar drain
      was placed when ICP was >20 mm Hg for an average of 3 hours despite the
      optimization of the aforementioned parameters. RESULTS: After lumbar drain
      placement, ICP was reduced from a mean of 28.2 +/- 6.5 mm Hg to 10.1 +/- 7.1 mm
      Hg (P <0.001). Requirements for hyperosmolar therapy, sedatives, and paralytics
      were also significantly decreased (P < 0.05) after lumbar drain placement. One
      patient had unilateral papillary changes four hours after lumbar drain placement.
      The pupil returned to its normal state after decompressive craniectomy. There was
      no incidence of CSF infection. Three of the 15 patients died during the study
      period. CONCLUSIONS: This study shows the beneficial role of lumbar cerebrospinal
      fluid drainage as an effective and safe treatment modality for elevated ICP.

PMID- 22154152
TI  - Patients with recurrent ischaemic events from carotid artery disease have a large
      lipid core and low GSM.
AB  - OBJECTIVES: The aim of the current study was to determine whether computerised
      ultrasound plaque analysis could identify features predictive of an increased
      risk of early recurrent events after symptom onset. METHODS: Between August 2008
      and December 2010, 158 consecutive symptomatic patients undergoing carotid
      endarterectomy (CEA) had their plaques harvested at CEA and then independently
      scored for markers of histological plaque instability. Duplex ultrasound images
      recorded prior to CEA were independently assessed using the Iconsoft software.
      RESULTS: One hundred and fifty eight recently symptomatic patients underwent CEA
      with 118 (75%) undergoing their operation within 14 days of their most recent
      clinical event. Twenty (12.7%) suffered a recurrent cerebral ischaemic event
      following admission to the vascular unit and before undergoing CEA. Using
      multivariate stepwise analysis; lipid core (OR 4.00, 95% CI 1.07 to 14.83, P =
      0.042) and a low GSM (OR 6.21, 95% CI 1.86 to 20.4, P = 0.003) were independently
      associated with recurrent cerebrovascular events. CONCLUSION: Within a cohort of
      patients presenting with recent onset cerebral ischaemic events undergoing CEA,
      the plaques of patients with recurrent events following admission to hospital had
      evidence a large lipid core and a low GSM.

PMID- 22154153
TI  - Trastuzumab treatment in multiple lines: current data and future directions.
AB  - Trastuzumab improves response rate, time to progression, and overall survival
      when combined with first-line chemotherapy in patients with human epidermal
      growth factor receptor 2-positive (HER2-positive) metastatic breast cancer (MBC).
      However, the benefits of continuing trastuzumab beyond disease progression have
      not been clearly established. The literature was reviewed to obtain data on
      trastuzumab use beyond disease progression. In general, data from retrospective
      and observational studies suggest that there may be clinical benefit when
      trastuzumab is used beyond disease progression. These results are supported by
      prospective non-randomized studies. Response rates and survival outcomes have
      generally been superior in patients who have continued trastuzumab after disease
      progression compared with those who have not. Moreover, recent data from two
      prospective randomized phase III trials have shown that adding trastuzumab to the
      treatment regimen in patients with MBC who have progressed on trastuzumab-based
      therapy significantly prolongs progression-free survival. Emerging evidence from
      randomized controlled trials supports the potential clinical utility of
      continuing trastuzumab-based therapy beyond progression and supports the National
      Comprehensive Cancer Network recommendation to consider this treatment approach.
      Future treatment of HER2-positive MBC may involve trastuzumab being used in
      successive regimens in combination with other targeted therapies.

PMID- 22154155
TI  - Hyperaccumulation of zinc by Corydalis davidii in Zn-polluted soils.
AB  - A field survey was conducted to identify potential Zn accumulators from an
      artisanal Zn smelting area in southwest China's Guizhou Province. Hydroponic and
      soil culture experiments were performed to investigate the accumulation ability
      of Zn in Corydalis davidii. Zn concentrations in roots, stems and leaves of C.
      davidii in the smelting site were 1.1-3.5, 1.2-11.2, and 3.3-14 mg g(-)(1),
      respectively, whereas Zn concentrations in roots, stems and leaves of C. davidii
      in the contaminated site impacted by the Zn smelting were 1.0-2.4, 1.9-6.5, and
      3.0-1.1 mg g(-1), respectively. Zn concentrations in leaves and stems of C.
      davidii were observed at above 10 mg g(-1) that refers to the threshold of Zn
      hyperaccumulator. The concentration distribution of Zn in C. davidii was
      leaf>stem>root, and the Zn bioaccumulation factors of C. davidii were above 1. It
      is concluded that C. davidii has high tolerance to concentrate Zn stress, and
      that C. davidii is a newly discovered Zn-hyperaccumulator with high biomass in
      the aboveground parts. Based on the cultivation experiments, C. davidii could
      reduce Zn concentration by 26.6, 21.2, and 10.2 mg kg(-1)yr(-1) by
      phytoextraction from the smelting slag, Zn-contaminated soil, and background
      soil, respectively.

PMID- 22154156
TI  - Behaviour of pharmaceuticals in spiked lake sediments - effects and interactions
      with benthic invertebrates.
AB  - The behaviour and effects of atorvastatin (ATO), carbamazepine (CBZ), and 17alpha
      ethinylestradiol (EE2) were investigated in spiked lake sediments, at
      concentrations up to 56.5 mg kg(-1)dry weight (dw), with the benthic
      invertebrates Chironomus dilutus and Hyalella azteca. Desorption constants were
      calculated in the presence and absence of animals, using linear isotherms,
      yielding K(d) values of 28.2, 189.0 and 125.1 L kg(-1) (ATO), 73.7, 201.7 and
      263.2 L kg(-1) (CBZ), and 114.9, 114.2 and 519.2 L kg(-1) (EE2) for C. dilutus,
      H. azteca, and without animals, respectively. For ATO and CBZ, K(d) values were
      smaller in the presence of C. dilutus, indicating greater desorption to the
      overlying water from bioturbation, which is consistent with the predominantly
      benthic occurrence of C. dilutus compared to H. azteca. In contrast, due to its
      greater hydrophobicity, bioturbation did not significantly affect desorption of
      EE2. No significant toxicity was observed, indicating decreased bioavailability
      of the chemicals sorbed to sediments compared with water-only toxicity assays.

PMID- 22154154
TI  - Growing the growth cone: remodeling the cytoskeleton to promote axon
      regeneration.
AB  - Axon growth is driven by the movement of a growth cone, a specialized sensory
      motile structure located at the tip of a growing neurite. Although stalled
      retraction bulbs have long been recognized as hallmarks of regeneration failure,
      mechanisms that control the formation and migration of nerve endings are only
      beginning to be unraveled. Recent studies point to microtubules as key
      determinants for such processes, and emerging evidence suggests that regulators
      of actin and microtubule dynamics in the growth cone might serve as attractive
      targets for controlling both the speed and trajectory of regenerating axons. This
      review discusses the potential of and recent progress in direct modulation of the
      growth cone machinery as a novel strategy to promote axon regeneration in the
      nervous system after injury.

PMID- 22154157
TI  - Atmospheric pollution in an urban environment by tree bark biomonitoring - part
      II: Sr, Nd and Pb isotopic tracing.
AB  - The harmful effect of manmade particles on natural processes and human health is
      documented by a large number of studies showing a positive correlation between
      particulate matter (PM) concentration and health effects. Diminution of this
      health risk necessitates among others the precise knowledge of the particle
      sources, their physical and chemical properties and their dissemination in the
      environment. Pb isotope ratios have been successfully used during the past
      decades as tracers of anthropogenic Pb disseminated in the biosphere. Here we
      show that tree bark biomonitoring with lead (Pb), strontium (Sr) and neodymium
      (Nd) isotope ratios as tracers allow a thorough analysis of the impacts of
      industrial and other anthropogenic emissions on the urban environment. This is
      the first comprehensive multi-isotope tracer study of atmospheric pollution in an
      urban environment allowing to identify and to integrate the different plume paths
      of emissions in a digital map system. This innovative approach might become an
      important tool for environmental management and policy-making processes dealing
      especially with risks and surveillance of air quality in the urban environment.

PMID- 22154158
TI  - Occurrence of antibiotics in eight sewage treatment plants in Beijing, China.
AB  - The occurrence, removal efficiency and seasonal variation of 22 antibiotics,
      including eight fluoroquinolones, nine sulfonamides and five macrolides, were
      investigated in eight sewage treatment plants (STPs) in Beijing, China. A total
      of 14 antibiotics were detected in wastewater samples, with the maximum
      concentration being 3.1 MUg L(-1) in the influent samples and 1.2 MUg L(-1) in
      the effluent samples. The most frequently detected antibiotics were ofloxacin,
      norfloxacin, sulfadiazine, sulfamethoxazole, erythromycin and roxithromycin; of
      these, the concentration of ofloxacin was the highest in most of the influent and
      effluent samples. Eighteen antibiotics were detected in the sludge samples, with
      concentrations ranging from 1.0*10(-1) to 2.1*10(4) MUg kg(-1). The dominant
      antibiotics found in the sludge samples were the fluoroquinolones, with ofloxacin
      having the highest concentration in all the sludge samples. The antibiotics could
      not be removed completely by the STPs, and the mean removal efficiency ranged
      from -34 to 72%. Of all the antibiotics, the fluoroquinolones were removed
      comparatively more efficiently, probably due to their adsorption to sludge.
      Seasonal variation of the antibiotics in the sludge samples was also studied. The
      concentrations of antibiotics in winter were higher than in spring and autumn.
      Since the total levels of the fluoroquinolones detected in the influent samples
      were lower than the predicted no-effect concentration (PNEC) of 8.0 MUg L(-1),
      the residues of these antibiotics would be unlikely to have adverse effects on
      microorganisms involved in sewage treatment processes.

PMID- 22154159
TI  - A flow-through passive dosing system for continuously supplying aqueous solutions
      of hydrophobic chemicals to bioconcentration and aquatic toxicity tests.
AB  - A continuous supply of water with defined stable concentrations of hydrophobic
      chemicals is a requirement in a range of laboratory tests such as the OECD 305
      protocol for determining the bioconcentration factor in fish. Satisfying this
      requirement continues to be a challenge, particularly for hydrophobic chemicals.
      Here we present a novel solution based on equilibrium passive dosing. It employs
      a commercially available unit consisting of ~16000 polydimethylsiloxane (PDMS)
      tubes connected to two manifolds. The chemicals are loaded into the unit by
      repeatedly perfusing it with a methanol solution of the substances that is
      progressively diluted with water. Thereafter the unit is perfused with water and
      the chemicals partition from the unit into the water. The system was tested with
      nine chemicals with logK(OW) ranging from 4.1 to 6.3. The aqueous concentrations
      generated were shown to be largely independent of the water flow rate, and the
      unit to unit reproducibility was within a factor of ~2. In continuous flow
      experiments the aqueous concentrations of most of the study chemicals remained
      constant over 8d. A model was assembled that allows prediction of the operating
      characteristics of the system from the logK(OW) or PDMS/water partition
      coefficient of the chemical. The system is a simple, safe, predictable and
      flexible tool that generates stable aqueous concentrations of hydrophobic
      chemicals.

PMID- 22154160
TI  - Acute confusion in headache with neurologic deficits and cerebrospinal fluid
      lymphocytosis syndrome.
AB  - Abrupt headaches with focal neurologic deficits usually indicate medical
      emergencies that require advanced investigations and prompt treatment. The
      distinct syndrome of "headache with neurologic deficits and cerebrospinal fluid
      lymphocytosis" (HaNDL) is infrequent and considered a benign, self-limited
      disorder. We illustrated a 29-year-old man with HaNDL atypically presenting as
      episodic altered consciousness rather than sensorimotor prodromes. The diagnosis
      was made carefully by exclusion of other likely entities. It is important for
      clinical physicians to differentiate HaNDL from other potentially fatal.

PMID- 22154161
TI  - Much ado about nothing.
AB  - Thirty-year-old woman with history of AIDS and anxiety presented with
      palpitations. Although clinically euvolemic, she was aggressively fluid
      resuscitated in lieu of sinus tachycardia. She developed unilateral pulmonary
      edema on account of left decubitus positioning and volume resuscitation. Given
      her normal cardiac, renal, and liver status, she spontaneously cleared the extra
      fluid, and the pulmonary edema resolved. This case highlights the importance of
      recognizing transient unilateral pulmonary edema and need for early radiographs
      to document clearance and prevent unnecessary testing.

PMID- 22154162
TI  - Usefulness of chest ultrasonography in detecting pulmonary embolism in patient
      with chronic obstructive pulmonary disease and chronic renal failure: a case
      report.
AB  - We describe the case of a 75-year-old man affected by a chronic obstructive
      pulmonary disease and chronic renal failure admitted to our emergency department
      for dyspnea and interscapular stabbing pain. Chest radiography showed diffuse
      parenchymal consolidation in the lower right lung with bronchiectasis, but the
      treatment for infection disease did not improve the clinical conditions of the
      patient. According to Wells score indicating an intermediate risk for pulmonary
      embolism, we performed a chest ultrasonography that showed ultrasonographic
      patterns of thromboembolism. Because the presence of chronic renal failure
      limited the execution of a helical computed tomographic pulmonary angiography, a
      pulmonary scintigraphy was performed confirming the diagnosis of pulmonary
      embolism. Our case suggested that chest ultrasonography can be a valuable tool
      for early detection of pulmonary embolism and to establish immediately an
      appropriate therapy.

PMID- 22154163
TI  - The role of toxin A and toxin B in the virulence of Clostridium difficile.
AB  - During the past decade, there has been a striking increase in Clostridium
      difficile nosocomial infections worldwide predominantly due to the emergence of
      epidemic or hypervirulent isolates, leading to an increased research focus on
      this bacterium. Particular interest has surrounded the two large clostridial
      toxins encoded by most virulent isolates, known as toxin A and toxin B. Toxin A
      was thought to be the major virulence factor for many years; however, it is
      becoming increasingly evident that toxin B plays a much more important role than
      anticipated. It is clear that further experiments are required to accurately
      determine the relative roles of each toxin in disease, especially in more
      clinically relevant current epidemic isolates.

PMID- 22154164
TI  - MreB: pilot or passenger of cell wall synthesis?
AB  - The discovery that the bacterial cell shape determinant MreB is related to actin
      spurred new insights into bacterial morphogenesis and development. The
      trafficking and mechanical roles of the eukaryotic cytoskeleton were hypothesized
      to have a functional ancestor in MreB based on evidence implicating MreB as an
      organizer of cell wall synthesis. Genetic, biochemical and cytological studies
      implicate MreB as a coordinator of a large multi-protein peptidoglycan (PG)
      synthesizing holoenzyme. Recent advances in microscopy and new biochemical
      evidence, however, suggest that MreB may function differently than previously
      envisioned. This review summarizes our evolving knowledge of MreB and attempts to
      refine the generalized model of the proteins organizing PG synthesis in bacteria.
      This is generally thought to be conserved among eubacteria and the majority of
      the discussion will focus on studies from a few well-studied model organisms.

PMID- 22154165
TI  - Preoperative radiation therapy for upper rectal cancer T3,T4/Nx: selectivity
      essential.
AB  - This review explores the current available literature regarding the role of
      neoadjuvant therapy for upper locally advanced rectal cancers (>=10 cm-15 cm).
      Although there is a paucity of data evaluating the outcomes of preoperative
      chemoradiation for upper rectal cancers the authors suggest that T3N0 tumors will
      not likely benefit from radiation and that treatment of T4N0 should be
      individualized.

PMID- 22154166
TI  - Nonenzymatic continuous glucose monitoring in human whole blood using electrified
      nanoporous Pt.
AB  - This paper describes the first devised method for the nonenzymatic and
      electrochemical glucose monitoring in 100% human whole blood and serum. The
      nanoporous Pt electrode allows for the selective amplification of glucose
      oxidation in the presence of electroactive interfering species without the need
      for enzymatic reaction. The outer membrane was particularly optimized to allow
      glucose molecules to be electrochemically detected against the numerous
      constituents of human blood. The proposed sensor provided reproducible
      amperometric responses to glucose in human serum and whole blood. Its sensitivity
      was maintained for at least 7h under constantly electrified conditions, and
      continued to work properly after 30 days of storage in human whole blood and
      serum. Unlike the enzyme-based glucose sensors, it was found to be minimally
      affected by thermal fluctuation, so as to remain successful even after steam
      sterilization at high temperature (134  degrees C) and pressure (0.22 Mpa). The
      unprecedented long-term stability and sterilization compatibility observed herein
      suggest a promising alternative to conventional enzymatic glucose sensors for
      many analytical and clinical applications, particularly for continuous glucose
      monitoring devices designed to potentially lead to a closed-loop artificial
      pancreas by combining them with an insulin pump.

PMID- 22154167
TI  - Layer-by-layer self-assembly and electrochemistry: applications in biosensing and
      bioelectronics.
AB  - This paper provides an overview of different nanostructured architectures
      utilised in electrochemical devices and their application in biosensing and
      bioelectronics. Emphasis is placed on the fabrication of nanostructured films
      based on a layer-by-layer (LBL) films approach. We discuss the theory and the
      mechanism of charge transfer in polyelectrolyte multilayer films (PEM), as well
      as between biomolecules and redox centres, for the development of more sensitive
      and selective biosensors. Further, this paper presents an overview of topics
      involving the interaction between nanostructured materials, including metallic
      nanoparticles and carbon materials, and their effects on the preservation of the
      activity of biological molecules immobilised on electrode surfaces. This paper
      also presents examples of biological molecules utilised in film fabrication, such
      as DNA, several kinds of proteins, and oligonucleotides, and of the role of
      molecular interaction in biosensing performance. Towards the utilisation of LBL
      films, examples of several architectures and different electrochemical approaches
      demonstrate the potential of nanostructured LBL films for several applications
      that include the diagnosis and monitoring of diseases. Our main aim in this
      review is to survey what can assist researchers by presenting various approaches
      currently used in the field of bioelectrochemistry utilising supramolecular
      architectures based on an LBL approach for application in electrochemical
      biosensing.

PMID- 22154168
TI  - Multienzyme microbiosensor based on electropolymerized o-phenylenediamine for
      simultaneous in vitro determination of acetylcholine and choline.
AB  - The electrochemical biosensors based on poly(o-phenylenediamine) (PoPD) and
      acetylcholinesterase (AChE) and choline oxidase (ChO) enzymes were fabricated on
      carbon fibre (CF) substrate. The electropolymerized PoPD was used to reduce the
      interfering substances. The electrode assembly was completed by depositing
      functionalized carbon nano tubes (FCNTs) and Nafion (Naf). Amperometric detection
      of acetylcholine (ACh) and choline (Ch) were realized at an applied potential of
      +750 mV vs Ag/AgCl (saturated KCl). At pH 7.4, the final assembly, Naf-FCNTs/AChE
      ChO((10:1))/PoPD/CF(Elip), was observed to have high sensitivity towards Ch
      (6.3+/-0.3 MUA mM(-1)) and ACh (5.8+/-0.3 MUA mM(-1)), linear range for Ch
      (K(M)=0.52+/-0.03 mM) and ACh (K(M)=0.59+/-0.07 mM), and for Ch the highest
      ascorbic acid blocking capacity (97.2+/-2 1mM AA). It had a response time of <5s
      and with 0.045 MUM limit of detection. Studies on different ratio (ACh/Ch)
      revealed that 10:1, gave best overall response.

PMID- 22154169
TI  - Label-free detection of Staphylococcus aureus in skin using real-time
      potentiometric biosensors based on carbon nanotubes and aptamers.
AB  - In this paper we report the first biosensor that is able to detect Staphylococcus
      aureus in real-time. A network of single-walled carbon nanotubes (SWCNTs) acts as
      an ion-to-electron potentiometric transducer and anti-S. aureus aptamers are the
      recognition element. Carbon nanotubes were functionalized with aptamers using two
      different approaches: (1) non-covalent adsorption of drop-casted pyrenil-modified
      aptamers onto the external walls of the SWCNTs; and (2) covalent bond formation
      between amine-modified aptamers and carboxylic groups previously introduced by
      oxidation at the ends of the SWCNTs. Both of these approaches yielded functional
      biosensors but there were large differences in the minimum detectable bacteria
      concentration and sensitivity values. With covalent functionalization, the
      minimum concentration detected was 8*10(2)colony-forming units (CFU)/mL and the
      sensitivity was 0.36 mV/Decade. With the non-covalent approach, the sensitivity
      was higher (1.52 mV/Decade) but the minimum concentration detected was greatly
      affected (10(7) CFU/mL). In both cases, potential as a function of Decade of
      bacteria concentration was linear. Functional biosensors were used to test real
      samples from freshly excised pig skin, contaminated with the target
      microorganism, as a surrogate for human skin.

PMID- 22154170
TI  - Emphysematous pyelonephritis with complete duplication of the left urinary tract.
AB  - Emphysematous pyelonephritis (EPN) is a life-threatening bacterial infection and
      should be treated rapidly and carefully. We report a case of EPN with complete
      duplication of the left urinary tract. A 68-year-old woman was admitted to our
      hospital complaining of high-grade fever and left flank pain. An abdominal
      computed tomography scan showed gas was presented in the renal parenchyma, not
      only the pelvis and ureter. Based on these findings, a diagnosis of left EPN was
      made. A partial nephrectomy of the affected left upper pole moiety was performed
      and the patient underwent additional medical management. Other 83 cases of EPN
      from the Japanese literature were reviewed.

PMID- 22154171
TI  - The role of resection of pulmonary metastases from prostate cancer: a case report
      and literature review.
AB  - We report a case of a 53-year-old man who presented with two nodules in the lower
      lobe and one nodule in the upper lobe of the right lung almost 7 years after
      radical prostatectomy for pT3aN0M0, Gleason 4+5 disease, without evidence of
      osseous or lymphatic spread. Surgical resection of the lower lung nodules
      confirmed metastases, but prostate-specific antigen did not drop to undetectable
      levels. Isolated pulmonary metastases from prostate cancer are rare with only 33
      previously described cases in the English-language literature, 18 of which were
      solitary metastases. We review the principles of management, including
      metastasectomy and long-term prognosis.

PMID- 22154172
TI  - Synchronous metastatic seminoma and primary retroperitoneal ganglioneuroma: case
      report and literature review.
AB  - Testicular cancer is the most common malignancy in young men with seminomas
      comprising almost half of all germ cell tumours. Benign ganglioneuromas are rare
      tumours derived from the sympathetic nervous system. They usually occur in
      aldolescents and young adults and are predominantly located in the mediastinum
      and retroperitoneum. We report a case of a patient with synchronous metastatic
      testicular seminoma with retroperitoneal lymph node involvement and a benign
      retroperitoneal ganglioneuroma (RGN) which caused diagnostic and management
      challenges. The patient had a complete response following combination
      chemotherapy for his seminoma and subsequently underwent complete resection of
      his ganglioneuroma.

PMID- 22154173
TI  - Epididymal germinoma: Reality or myth?
AB  - Epididymal tumours are rare, but definite pathological entity. Most tumours are
      benign, however, malignant lesions have also been reported. The common benign
      tumours are either leiomyomas or adenomatoid tumours. Malignant pathologies
      include primary epididymal adenocarcinoma, liposarcoma, leiomyosarcoma, malignant
      fibrous histiocytoma, mesothelioma and lymphoma. We present a case of a 45-year
      old male referred urgently for suspected scrotal mass which on ultrasonography
      showed a lesion in the left epididymal head (possible granuloma).

PMID- 22154174
TI  - An unusual surgical success with a defective penile prosthesis.
AB  - A defective penile prosthesis is disconcerting for the surgeon performing an
      implantation in a patient with erectile dysfunction. We became aware of the
      defective Titan penile prosthesis just after insertion of the left cylinder,
      which had an abnormal rotation (180 degrees) due to abnormal rotated tubing,
      which occurred at the manufacturing plant. We successfully performed the
      implantation by cutting and re-connecting the tubing between the cylinder and
      pump with a spare connector. When the surgeon encounters a defective penile
      prosthesis with abnormal rotation of the cylinder due to abnormal rotated tubing
      in the operative field, disconnection and re-connection of the tubing using an
      extra connector are alternative cost-effective maneuvers.

PMID- 22154175
TI  - A simple technique for ureteral orifice dilatation in rigid ureterorenoscopy for
      distal ureteral stones.

PMID- 22154176
TI  - Leiomyosarcoma of the epididymis: 2 cases and review of the literature.
AB  - Paratesticular leiomyosarcomas are rare. We report two cases of leiomyosarcoma of
      the epididymis diagnosed and treated in a regional community hospital in Canada
      in 2009 and 2010. Both patients were males of ages 58 and 75, respectively. They
      presented with painless masses which, on ultrasonography, appeared to be solid
      masses demonstrating blood flow. Each patient underwent trans-scrotal resection
      of the affected epididymis. Pathological examination of trans-scrotal
      epididymectomy specimens confirmed the diagnosis of high-grade leiomyosarcoma.
      Leiomyosarcoma is an important differential diagnosis for paratesticular masses
      in the elderly male; the primary treatment is radical inguinal orchiectomy with
      high ligation of the spermatic cord.

PMID- 22154177
TI  - Simple nephrectomy in a young woman for recurrent pyelonephritis utilizing
      laparoendoscopic single-site surgery (LESS).
AB  - Minimally invasive surgery is rapidly evolving due to new technology and
      techniques designed to improve patient outcomes. We report a case of a young
      woman with an atrophic kidney secondary to reflux nephropathy, suffering from
      recurrent episodes of pyelonephritis. She was treated successfully using
      laparoendoscopic single-site surgery (LESS). We also present a review of the
      literature.

PMID- 22154178
TI  - Legionella pneumonia presenting with bilateral flank pain, hyponatraemia and
      acute renal failure.
AB  - Legionnaires' disease (LD) is an often overlooked but a possible cause of
      sporadic community acquired pneumonia. High fever, cough and gastrointestinal
      symptoms are non-specific symptoms. Hyponatremia is more common in LD than
      pneumonia linked with other causes. A definitive diagnosis is usually confirmed
      by culture, urinary antigen testing for Legionella species. Macolide or quinolone
      antibiotic is the treatment of choice. We describe a case of Legionella pneumonia
      presenting with high fever, bilateral flank pain and oliguria. It is important
      for clinicians to be aware of this diagnosis when managing patients with flank
      pain. The case highlights the problems in differentiating LD from renal colic and
      the importance of proper history, physical examination with laboratory tests for
      appropriate management.

PMID- 22154179
TI  - Transthoracic approach for liver tumors.
AB  - Abdominal approach is commonly used for resection of liver tumors. However, in
      rare cases, transthoracic approach may be a valuable option for management of
      lesions located in the hepatic dome or involving the cavo-hepatic junction for
      very selected patients. This approach can be an open procedure (thoracotomomy), a
      video-assisted minimally invasive technique (thoracoscopy), or a strictly
      percutaneously treatment (CT-guided radiofrequency ablation). This approach seems
      useful for high-risk patients, with previous major abdominal surgery, or awaiting
      for liver transplantation (bridge concept) with cranially located single lesions.
      A limited liver resection (tumorectomy or segmentectomy) can be performed, but
      this approach is also suitable for percutaneous ablation therapy (radiofrequency
      or cryotherapy), with an acceptable morbidity.

PMID- 22154180
TI  - Environmental injustices of children's exposure to air pollution from road
      transport within the model British multicultural city of Leicester: 2000-09.
AB  - The significant contribution of road-transport to air pollution within the urban
      arena is widely acknowledged, and traditionally explored in relation to health
      outcomes across a temporal scale. However, the structure of the urban environment
      is also of importance in dictating the existence of extremely variable traffic
      pollutant levels, which often tend to be linked with social disparities.
      Nevertheless 'Environmental Justice' studies have rarely tackled the adverse
      health implications of exposures from mobile sources (Chakraborty, 2009), or have
      applied statistical techniques that are appropriate for such spatial data
      (Gilbert and Chakraborty, 2011). This article addresses these gaps by spatially
      examining the distribution of respiratory hospitalisation incidents of children
      aged 0-15 years in relation to social circumstances and residential exposures of
      annual PM(10) road-transport emissions within Leicester during 2000-09.
      Continuing upon the theme of 'Environmental Justice', the research explores the
      intra-urban spatial distribution of those who produce and residentially
      experience the majority of road-transport emissions. The findings indicate
      significant global relationships to exist between children's hospitalisation
      rates and social-economic-status, ethnic minorities, and PM(10) road-transport
      emissions within Leicester. Local Indicators of Spatial Association (LISA) and
      Geographically Weighted Regression (GWR) identified important localised
      variations within the dataset, specifically relating to a double-burden of
      residentially experienced road-transport emissions and deprivation effecting
      inner city children's respiratory health. Furthermore, affluent intra-urban
      communities tended to contribute the highest levels of emission from private
      transport, while residentially experiencing relatively low exposure of transport
      emissions. This would suggest that environmental injustices prevail across the
      model British multicultural city of Leicester.

PMID- 22154181
TI  - Assessing and monitoring urban resilience using COPD in Porto.
AB  - BACKGROUND: COPD morbidity is a good example of how the urban form may interfere
      with a disease's severity. Then, it may play an important role as a stimulus to
      increase the acceptability of several policy actions that aim to upgrade urban
      resilience. Despite the multiple dimensions of wellbeing, health is surely a key
      variable attracting everyone's attention, which is thus more likely to be able to
      persuade people that actions that may at first seem undesirable are fundamental
      in improving urban sustainability and well-being. METHODS: After creating a short
      list of socio-economic and environmental factors relating to the onset and
      aggravation of COPD, daily admissions distributions were compared using both a
      non-weighted and a weighted multi-criteria hierarchical analysis procedure.
      RESULTS: Porto's COPD Social and Environmental Inequalities Index (SEII),
      calculated with a hierarchical analysis procedure, accurately illustrates a great
      relationship between COPD admissions and adverse urban form variables.
      CONCLUSION: COPD may be an important communication tool to stimulate the
      acceptability of some otherwise unpopular planning measures to improve urban
      resilience (sustainability and well-being).

PMID- 22154182
TI  - Environmental assay on the effect of poultry manure application on soil organisms
      in agroecosystems.
AB  - This paper reports the effects produced on the organisms of the soil (plants,
      invertebrates and microorganisms), after the application of two types of poultry
      manure (sawdust and straw bed) on an agricultural land. The test was made using a
      terrestrial microcosm, Multi-Species Soil System (MS3) developed in INIA. There
      was no difference in the germination for any of the three species of plants
      considered in the study. The biomass was increased in the wheat (Triticum
      aestivum) coming from ground treated with both kinds of poultry manure. Oilseed
      rape (Brasica rapa) was not affected and regarding vetch (Vicia sativa) only
      straw poultry manure showed significant difference. For length only Vicia sativa
      was affected showing a reduction when straw was exposed to poultry manure. When
      the effect on invertebrates was studied, we observed a reduction in the number of
      worms during the test, especially from the ground control (13.7%), higher than in
      the ground with sawdust poultry manure (6.7%), whereas in the ground with straw
      poultry manure, there was no reduction. The biomass was affected and at the end
      of the test it was observed that while the reduction of worms in the ground
      control was about 48%, the number of those that were in the ground with sawdust
      poultry manure or straw poultry manure decreased by 41% and 22% respectively.
      Finally, the effects on microorganisms showed that the enzymatic activities:
      dehydrogenase (DH) and phosphatase and basal respiration rate increased at the
      beginning of the test, and the differences were statistically significant
      compared with the values of the control group. During the test, all these
      parameters decreased (except DH activities) but they were always higher than in
      the ground control. This is why it is possible to deduce that the contribution of
      poultry manure caused an improvement in the conditions of fertilization and also
      for the soil.

PMID- 22154183
TI  - Impact of bacterial and fungal processes on 14C-hexadecane mineralisation in
      weathered hydrocarbon contaminated soil.
AB  - In this study, the impact of bacterial and fungal processes on (14)C-hexadecane
      mineralisation was investigated in weathered hydrocarbon contaminated soil. The
      extent of (14)C-hexadecane mineralisation varied depending on the bioremediation
      strategy employed. Under enhanced natural attenuation conditions, (14)C
      hexadecane mineralisation after 98 days was 8.5 +/- 3.7% compared to <1.2%
      without nitrogen and phosphorus additions. (14)C-hexadecane mineralisation was
      further enhanced through Tween 80 amendments (28.9 +/- 2.4%) which also promoted
      the growth of a Phanerochaete chyrsosporium fungal mat. Although fungal growth in
      weathered hydrocarbon contaminated soil could be promoted through supplementing
      additional carbon sources (Tween 80, sawdust, compost, pea straw), fungal (14)C
      hexadecane mineralisation was negligible when sodium azide was added to soil
      microcosms to inhibit bacterial activity. In contrast, when fungal activity was
      inhibited through nystatin additions, (14)C-hexadecane mineralisation ranged from
      6.5 +/- 0.2 to 35.8 +/- 3.8% after 98 days depending on the supplied amendment.
      Bacteria inhibition with sodium azide resulted in a reduction in bacterial
      diversity (33-37%) compared to microcosms supplemented with nystatin or
      microcosms without inhibitory supplements. However, alkB bacterial groups were
      undetected in sodium azide supplemented microcosms, highlighting the important
      role of this bacterial group in (14)C-hexadecane mineralisation.

PMID- 22154184
TI  - Halogenated organic contaminants and their correlations with circulating thyroid
      hormones in developing Arctic seabirds.
AB  - Thyroid hormones are essential for normal growth and development and disruption
      of thyroid homeostasis can be critical to young developing individuals. The aim
      of the present study was to assess plasma concentrations of halogenated organic
      contaminants (HOCs) in chicks of two seabird species and to investigate possible
      correlations of HOCs with circulating thyroid hormone (TH) concentrations. Plasma
      from black-legged kittiwake (Rissa tridactyla) and northern fulmar (Fulmarus
      glacialis) chicks were sampled in Kongsfjorden, Svalbard in 2006. The samples
      were analyzed for thyroid hormones and a wide range of HOCs (polychlorinated
      biphenyls (PCBs), hydroxylated (OH-) and methylsulphoned (MeSO-) PCB metabolites,
      organochlorine pesticides (OCPs), brominated flame retardants (BFRs), and
      perfluorinated compounds (PFCs)). Concentrations of HOCs were generally low in
      kittiwake and fulmar chicks compared to previous reports. HOC concentrations were
      five times higher in fulmar chicks compared to in kittiwake chicks. PFCs
      dominated the summed HOCs concentrations in both species (77% in kittiwakes and
      69% in fulmars). Positive associations between total thyroxin (TT4) and PFCs
      (PFHpS, PFOS, PFNA) were found in both species. Although correlations do not
      implicate causal relationships per se, the correlations are of concern as
      disruption of TH homeostasis may cause developmental effects in young birds.

PMID- 22154185
TI  - Particulate characteristics and emission rates during the injection of class B
      biosolids into an agricultural field.
AB  - A field study was conducted during the summer of 2009 to collect airborne
      particulate matter emitted during the agricultural activities. The activities
      surrounding the injection application of class B biosolids were targeted for the
      sampling. The sampling was carried out before (pre-application), during
      (application), and after (post-application) the application. This study
      characterized the particulate emissions deposited on the aerosols spectrometer.
      The effect of different biosolids related activities was significant on the mass
      concentration, the number concentration, and the size distribution. The mass
      concentration of fine (PM(2.5)) and ultrafine (PM(1.0)) was highest during the
      pre-application. The mass concentration of thoracic fraction (PM(2.5-10))
      increased significantly during the application. A bimodal size distribution was
      observed throughout the sampling. Nuclei mode formation was predominant during
      the pre-application and the post-application, whereas the accumulation mode was
      distinctive during the application. The number concentration of ultrafine
      particles was highest during the entire sampling period. The application of
      biosolids resulted into a higher number of coarse particle emission. It was also
      observed that the ultrafine and fine particles traveled longer downwind
      distances. The emission rates were determined for pre-application, application,
      and post-application activities.

PMID- 22154187
TI  - How to select the optimal therapy for early-stage prostate cancer.
AB  - Selecting the "optimal therapy" for the patient with localized prostate cancer
      may be one of the most challenging medical decisions facing the oncologist. Most
      patients will have a number of appropriate therapeutic options available to them.
      Before determining which therapy is most appropriate for a patient, a critical
      question which needs to be asked is whether any therapy is necessary, especially
      for those who present with early-stage, low-grade, low-volume disease.
      Furthermore, given the lack of randomized trials available to guide physicians
      regarding the superiority of one therapy over another, it is important to
      consider the different side-effect profiles relevant for each treatment modality.
      The potential toxicities of therapy impact quality-of-life outcomes and play an
      important role for most patients in their individual selection of a particular
      therapy. In addition, there are other important issues that need to be
      considered, which include the medical condition of the patient and emotional and
      psychological considerations, as well as family/peer viewpoints or perceived
      notions of a particular therapy. This review will discuss the relevant issues in
      the decision making and treatment selection for the patient.

PMID- 22154188
TI  - Functional imaging of non-motor signs in Parkinson's disease.
AB  - Non-motor signs encountered in Parkinson's disease consist in a heterogeneous
      group of manifestations including hyposmia, pain, fatigue, sleep disorders,
      neuropsychic disorders. Functional imaging techniques provide an invaluable
      method to understand their pathophysiology, allowing us to study the
      abnormalities of brain metabolism or perfusion associated with these
      manifestations or the underlying dysfunction of different neurotransmission
      systems. The present paper covers the recent advances provided by functional
      imaging in this area.

PMID- 22154189
TI  - Gender based differences in acute stroke care in Michigan hospitals.
AB  - BACKGROUND: We sought to examine whether gender-based differences in acute stroke
      care occur in both Joint Commission (JC) certified and noncertified hospitals.
      METHODS: 602 charts of patients with ischemic stroke were reviewed from five JC
      certified and five noncertified hospitals for gender differences in the
      prehospital factors, emergency department evaluation, in-hospital stroke care,
      discharge outcome and use of secondary prevention measures. RESULTS: More women
      arrived via ambulance (63.1% women vs. 53.9% men, p=0.025) while more men came by
      self-transportation (42.6% vs. 30%, p=0.0016). There was no difference by gender
      for evaluation for thrombolytics (89.4% men vs. 85.9% women) or intravenous t-PA
      administered (3.5% men vs. 2.5% women, p=0.82). More patients in JC certified
      centers were evaluated for thrombolysis than in noncertified centers. Delay in
      arrival was the commonest reason for not getting thrombolysis in both groups.
      More men than women had mild/resolving symptoms, had more interventional
      procedures, and better discharge outcome. More men were discharged on
      antithrombotics. Even after adjusting for age, gender differences were
      significant for arrival by ambulance, self transportation, mild/resolving
      symptoms, interventional procedures performed and marginally for good discharge
      outcome. CONCLUSION: There were significant gender differences in delivery of
      acute stroke care in Michigan hospitals even after adjustment for age
      differences. In spite of milder symptoms and less usage of emergency services,
      men received more aggressive stroke care with a tendency towards better discharge
      outcome. Going to a JC certified center was a better predictor of consideration
      for thrombolytics than gender.

PMID- 22154190
TI  - Antioxidant-enriched diet does not delay the progression of age-related hearing
      loss.
AB  - Oxidative stress has been linked to noise- and drug-induced as well as age
      related hearing loss. Antioxidants can attenuate the decline of cochlear
      structure and function after exposure to noise or drugs, but it is debated as to
      whether they can protect from age-related hearing loss. In a long-term
      longitudinal study, 10-month-old female CBA/J mice were placed on either a
      control or antioxidant-enriched diet and monitored through 24 months of age.
      Supplementation with vitamins A, C, and E, L-carnitine, and alpha-lipoic acid
      significantly increased the antioxidant capacity of inner ear tissues. However,
      by 24 months of age, the magnitude of hearing loss was equal between the two
      groups. Likewise, there were no significant differences in hair cell loss or
      degeneration of spiral ganglion cells. We conclude that dietary manipulations can
      alter cochlear antioxidant capacity but do not ameliorate age-related
      sensorineural hearing loss in the CBA/J mouse.

PMID- 22154191
TI  - Screening for VPS35 mutations in Parkinson's disease.
AB  - Recently 2 groups have independently identified a mutation in the gene 'vacuolar
      protein sorting 35 homolog' (VPS35 c.1858G>A; p.Asp620Asn) as a possible cause of
      autosomal dominant Parkinson's disease (PD). In order to assess the frequency of
      the reported mutation and to search for other possible disease-causing variants
      in this gene, we sequenced all 17 exons of VPS35 in 96 familial PD cases, and
      exon 15 (in which the reported mutation is found) in an additional 64 familial PD
      cases, 175 young-onset PD cases, and 262 sporadic, neuropathologically confirmed
      PD cases. We identified 1 individual with the p.Asp620Asn mutation and an
      autosomal dominant family history of PD. Subsequent follow-up of the family
      confirmed an affected sibling and cousin who also carried the same mutation. No
      other potentially disease-causing mutations were identified. We conclude that the
      VPS35 c.1858G>A mutation is an uncommon cause of familial Parkinson's disease in
      our population.

PMID- 22154192
TI  - Lipopolysaccharide mediated mast cells induce IL-10 producing regulatory T cells
      through the ICOSL/ICOS axis.
AB  - The mechanisms by which mast cells (MCs) regulate immune responses are still
      largely unknown. Here, we showed that MCs induced interleukin (IL)-10 producing T
      cells to regulate inflammatory responses. To gain insight into the molecules
      involved, we set up an in vitro system in which lipopolysaccharide (LPS)
      stimulated MCs and CD4(+) T cells were co-cultured. Induction of IL-10 producing
      regulatory T cells mainly relied on the inducible costimulator ligand
      (ICOSL)/ICOS axis. MCs stimulated with LPS for more than 6 weeks upregulated
      ICOSL expression, while icosl(-/-) BMMCs failed to induce IL-10 producing T
      cells. The LPS effect was mediated through NF-kappaB activation via the TLR4
      signaling pathway. Ex vivo analysis of bronchoalveolar lavage fluid from mice
      with LPS-mediated pneumonia revealed ICOSL(+) MCs and IL-10 producing T cell
      induction. Additionally, adaptive transfer of ICOSL(+) BMMCs attenuated LPS
      mediated inflammation in MC-deficient mice. This study provided new evidence for
      the regulatory role of MCs.

PMID- 22154194
TI  - Updated nomogram predicting lymph node invasion in patients with prostate cancer
      undergoing extended pelvic lymphadenectomy: optimizing a risk-adapted surgical
      approach.

PMID- 22154195
TI  - Uric acid level as a risk marker for metabolic syndrome: a Chinese cohort study.
AB  - OBJECTIVE: Despite some epidemiologic research demonstrating a positive
      relationship between serum uric acid (SUA) levels and the prevalence of metabolic
      syndrome (MetS), prospective data on SUA as a predictor of MetS incidence are
      limited. METHODS: The authors examined SUA as a risk marker for incident MetS in
      a prospective study of 3857 subjects who were free of MetS at baseline
      recruitment. Hyperuricemia was defined as SUA >=7.7 mg/dL for men and >=6.6 mg/dL
      for women. The MetS was defined according to a unified criteria set by several
      major organizations. RESULTS: During a mean follow-up of 5.41 years, 476
      participants developed MetS. A significantly stepwise increase in the incidence
      of MetS across tertiles of SUA was observed in the whole group (p for trend
      <0.001). Among women, this association was more robust than in men. After
      adjustment for age, variations of blood pressure, triglycerides, HDL-C, glucose,
      and waist circumference, females in the middle and upper tertiles of SUA had
      significantly higher risk of developing MetS when compared with subjects in the
      lowest tertile [adjusted-HR (95% CI) was 1.67 (1.12-2.49) and 3.18 (2.20-4.60),
      respectively; p for trend <0.001]. Overall, hyperuricemia was a significantly
      independent risk determinant for MetS in women, but it was a non-significant
      factor for MetS mediating waist circumference and serum triglycerides in men.
      CONCLUSION: SUA concentration is more closely associated with MetS in females
      than in males. Future investigations are needed to explore the underlying
      mechanisms involved in the sex-related association between SUA concentration and
      MetS risk.

PMID- 22154196
TI  - Antimicrobial susceptibility among gram-negative isolates collected from
      intensive care units in North America, Europe, the Asia-Pacific Rim, Latin
      America, the Middle East, and Africa between 2004 and 2009 as part of the
      Tigecycline Evaluation and Surveillance Trial.
AB  - BACKGROUND: The Tigecycline Evaluation and Surveillance Trial is an antimicrobial
      susceptibility surveillance program that collects gram-positive and gram-negative
      organisms globally. OBJECTIVE: This analysis reports on antimicrobial
      susceptibility among 23,918 gram-negative isolates collected from intensive care
      units globally between 2004 and 2009. METHODS: MICs and susceptibility were
      determined according to the guidelines of the Clinical and Laboratory Standards
      Institute (US Food and Drug Administration breakpoints were applied against
      tigecycline). RESULTS: Gram-negative isolates were collected from 6 geographical
      regions: North America, 8099 isolates; Europe, 9244; Asia-Pacific Rim, 1573;
      Latin America, 3996; the Middle East, 635; and Africa, 371. North America
      reported the lowest rates of extended-spectrum beta-lactamase (ESBL)-producing
      Klebsiella pneumoniae and Escherichia coli both overall (12.8% and 4.7%,
      respectively) and in each year of collection. High rates of ESBL production were
      reported among K pneumoniae from Latin America (45.5%) and Africa (54.9%) and for
      E coli from the Middle East (32.4%). Imipenem and tigecycline maintained >90%
      susceptibility against K pneumoniae, E coli, Klebsiella oxytoca, Enterobacter
      cloacae, and Serratia marcescens for all regions. Susceptibility to meropenem was
      >90% against all K oxytoca and S marcescens. Large regional variations in
      susceptibility among Acinetobacter baumannii were reported, with the largest
      variations reported for amikacin (75.2% in North America, 21.8% in the Middle
      East) and meropenem (60.4% in North America, 15.9% in Africa). MIC(90) values for
      tigecycline against A baumannii were low (1-2 mg/L) for all regions. Against P
      aeruginosa, susceptibility to amikacin (97.5% in North America, 67.5% in Latin
      America) and meropenem (79.1% in North America, 51.4% in Africa) had the largest
      variations. CONCLUSIONS: Antimicrobial resistance among gram-negative intensive
      care unit isolates was highly variable between geographic regions. The
      carbapenems were active in vitro against Enterobacteriaceae, A baumannii and P
      aeruginosa, and tigecycline continued to be active in vitro against members of
      the Enterobacteriaceae and A baumannii collected from intensive care units in
      North America, Europe, the Asia-Pacific Rim, Latin America, the Middle East, and
      Africa.

PMID- 22154197
TI  - Pharmacokinetics of betamethasone after single-dose intramuscular administration
      of betamethasone phosphate and betamethasone acetate to healthy subjects.
AB  - BACKGROUND: Betamethasone is used for its antiinflammatory and immunosuppressive
      effects in disorders of many organ systems. However, the pharmacokinetic
      properties of betamethasone in plasma after intramuscular injection of
      betamethasone sodium phosphate and betamethasone acetate dual-acting suspension
      need further investigation. OBJECTIVES: The main aim of this study was to
      determine the pharmacokinetic parameters of betamethasone, betamethasone acetate,
      and betamethasone phosphate after the administration of a single intramuscular
      dose of the dual-acting suspension to healthy human volunteers. METHODS: Two
      different studies were conducted in healthy males. Volunteers were judged healthy
      based on their medical history, physical examination, and laboratory test
      results. Before confinement, all volunteers were tested for freedom from alcohol
      and drugs of abuse. Following a 10-hour overnight fasting, a single dose of 1 mL
      of the dual-acting suspension containing 3 mg of betamethasone phosphate and 3 mg
      of betamethasone acetate was administered by intramuscular injection. Blood
      sampling covered 48 hours. The plasma samples obtained in the second study were
      stabilized to enable pharmacokinetic profiling of betamethasone esters. RESULTS:
      Twenty-four healthy males with mean (SD) age of 27 (6.62) years participated in
      each study. No incidences of serious adverse events were recorded during the
      studies. Six mild adverse events were reported in 2 subjects in the second study.
      One subject suffered from pain at the injection site and insomnia, and another
      subject complained of heartburn and drowsiness. Betamethasone phosphate appeared
      to be readily absorbed with a mean AUC(0-t) of 96.01 ng/h/mL and an AUC(0
      infinity) of 97.96 (23.38) ng/h/mL. Betamethasone peak plasma concentration
      reached a mean t(1/2) of 12.92 hours. Betamethasone acetate was not detected in
      the volunteers' plasma in either study (total of 2208 plasma samples).
      CONCLUSION: The observed pharmacokinetic parameters suggested that the acetate
      ester, and not the phosphate ester, of betamethasone acts as a prodrug or
      reservoir for betamethasone, conferring on it sustained- and extended-release
      characteristics.

PMID- 22154198
TI  - Long-term statin therapy in patients with systolic heart failure and normal
      cholesterol: effects on elevated serum markers of collagen turnover,
      inflammation, and B-type natriuretic peptide.
AB  - BACKGROUND: The role of statin therapy in heart failure (HF) is unclear. The
      amino-terminal propeptide of procollagen type III (PIIINP) predicts outcome in
      HF, and yet there are conflicting reports of statin therapy effects on PIIINP.
      OBJECTIVES: This study determined whether there was an increase in serum markers
      of inflammation, fibrosis (including PIIINP), and B-type natriuretic peptide
      (BNP) in patients with systolic HF and normal total cholesterol and determined
      the effects of long-term treatment with atorvastatin on these markers. METHODS:
      Fifty-six white patients with systolic HF and normal cholesterol levels (age 72
      [13] years; 68% male; body mass index 27.0 [7.3] kg/m(2); ejection fraction 35
      [13]%; 46% with history of smoking) were randomly allocated to atorvastatin
      treatment for 6 months, titrated to 40 mg/d (A group) or not (C group). Age-
      and/or sex-matched subjects without HF (N group) were also recruited. Biomarkers
      were measured at baseline (all groups) and 6 months (A and C groups). RESULTS:
      Serum markers of collagen turnover, inflammation, and BNP were significantly
      elevated in HF patients compared with normal participants (all P < 0.05). There
      were correlations between these markers in HF patients but not in normal
      subjects. Atorvastatin treatment for 6 months caused a significant reduction in
      the following biomarkers compared with baseline: BNP, from median (interquartile
      range) 268 (190-441) pg/mL to 185 (144-344) pg/mL; high-sensitivity C-reactive
      protein (hs-CRP), from 5.26 (1.95 -9.29) mg/L to 3.70 (2.34-6.81) mg/L; and
      PIIINP, from 4.65 (1.86) to 4.09 (1.25) pg/mL (all P < 0.05 baseline vs 6
      months). Between-group differences were significant for PIIINP only (P = 0.027).
      There was a positive interaction between atorvastatin effects and baseline hs-CRP
      and PIIINP (P < 0.01). CONCLUSIONS: Long-term statin therapy reduced PIIINP in
      this small, selected HF population with elevated baseline levels. Further
      evaluation of statin therapy in the management of HF patients with elevated
      PIIINP is warranted.

PMID- 22154199
TI  - Ulipristal acetate: review of the efficacy and safety of a newly approved agent
      for emergency contraception.
AB  - BACKGROUND: Emergency contraception (EC) is used to prevent unintended
      pregnancies. The current gold standard for oral EC is levonorgestrel (LNG)
      administered as a single 1.5-mg dose or in 2 doses of 0.75 mg separated by 12
      hours. LNG has shown to be effective up to 72 hours after coitus. Ulipristal
      acetate (UPA) is a selective progesterone receptor modulator approved for EC use
      in the United States in August 2010. UPA is administered as a one-time, 30-mg
      dose within 120 hours of intercourse. OBJECTIVE: The goal of this review was to
      provide a summary of the available literature on the use of UPA for EC. METHODS:
      PubMed, Cochrane Library, ClinicalTrials.gov, International Pharmaceutical
      Abstracts, EBSCO, and Iowa Drug Information Service were searched from February
      2011 through September 2011 to identify relevant articles. Search terms included
      ulipristal acetate, CDB-2914, VA 2914, and emergency contraception. RESULTS: In
      an open-label study, UPA was effective in preventing pregnancy in 1241 women who
      presented for EC up to 120 hours (5 days) after unprotected intercourse, with an
      observed pregnancy rate of 2.1% (95% CI, 1.4%-3.1%) versus 5.5% (ie, the expected
      pregnancy rate without EC). The efficacy of UPA did not decrease significantly (P
      = 0.44) over time, with pregnancy rates at intervals between >48 and 72 hours at
      2.3% (95% CI, 1.4%-3.8%), >72 and 96 hours at 2.1% (95% CI, 1.0%-4.1%), and >96
      and 120 hours at 1.3% (95% CI, 0.1%-4.8%). In a single-blind, comparative
      noninferiority study of 1696 women, UPA was at least as effective as LNG when
      used within 72 hours for EC, with 15 pregnancies in the UPA group and 22
      pregnancies in the LNG group (odds ratio = 0.68 [95% CI, 0.35-1.31]). In
      addition, UPA prevented significantly (P = 0.037) more pregnancies than LNG when
      used between 72 and 120 hours after unprotected intercourse, with 0 pregnancies
      in the UPA group and 3 pregnancies in the LNG group. In a meta-analysis, UPA
      prevented a greater percentage of pregnancies than LNG at intervals up to 24
      hours (0.9% UPA vs 2.5% LNG; P = 0.035), up to 72 hours (1.4% UPA vs 2.2% LNG; P
      = 0.046), and up to 120 hours (1.3% UPA vs 2.2% LNG; P = 0.025). The most
      commonly (>10%) reported adverse events included headache, nausea, and abdominal
      pain. In addition, UPA delayed onset of menstruation by a mean of 2.1 to 2.8
      days. CONCLUSIONS: Based on clinical trials, UPA seems to be a reasonably
      tolerable and effective method of EC when used within 120 hours of intercourse.
      UPA is at least as effective as LNG when used within the first 72 hours after
      unprotected intercourse. However, UPA may be more effective than LNG when used
      between 72 to 120 hours after unprotected intercourse, extending the window of
      opportunity for EC. UPA may provide a new option for women who require EC up to 5
      days after unprotected intercourse.

PMID- 22154200
TI  - Thirty-year follow-up of carnitine supplementation in two siblings with
      hypertrophic cardiomyopathy caused by primary systemic carnitine deficiency.

PMID- 22154201
TI  - Proteomic analysis of hemoglobin H-constant spring (Hb H-CS) erythroblasts.
AB  - Hemoglobin H disease (Hb H) arises through the loss or dysfunction of three of
      the four alpha globin genes through the co-inheritance of either gross gene
      deletions or an abnormal hemoglobin which causes a non-deletional loss of alpha
      globin expression. This study sought to investigate erythropoiesis in Hb H
      Constant Spring (Hb H-CS) disease, a common form of Hb H disease in Southeast
      Asia, caused by the inheritance of the Constant Spring variant hemoglobin
      together with deletion of two of the alpha globin genes. In comparison to normal
      erythroblasts, Hb H-CS erythroblasts showed reduced cell expansion although no
      difference in differentiation was observed. Proteomic analysis revealed the
      increased expression of both chaperone and chaperonin proteins as well as down
      regulation of proteins regulating apoptosis. Both chaperone and chaperonin
      mediated folding require ATP, and evidence of increase energy demand was seen in
      the form of increased expression of enzymes involved in purine biosynthesis and
      increased levels of reactive oxygen species. A significant increase in apoptosis
      was seen in Hb H-CS erythroblasts, and the results from the proteomic analysis
      suggest that this arises at least in part from the consequences of increased
      folding requirements in the Hb H-CS erythroblast.

PMID- 22154202
TI  - Clinical outcomes of 114 patients who underwent gamma-knife radiosurgery for
      medically refractory idiopathic trigeminal neuralgia.
AB  - The optimal radiation dose and target of Gamma-knife radiosurgery (GKRS) for
      medically refractory idiopathic trigeminal neuralgia (TN) are contentious. We
      investigated the effects and trigeminal nerve deficits of GKRS using two
      isocenters to treat a great length of the trigeminal nerve. Between January 2005
      and March 2010, 129 patients with idiopathic TN underwent GKRS at the West China
      Hospital of Sichuan University. A maximum central dose of 80-90 Gy was delivered
      to the trigeminal nerve root with two isocenters via a 4mm collimator helmet. One
      hundred and fourteen patients were followed-up periodically by telephone
      interview to determine the effects, trigeminal nerve deficits and time to the
      onset of pain relief. The mean follow-up duration was 29.6 months. One hundred
      and nine patients had complete or partial pain relief and the treatment failed in
      five patients. Nine patients experienced a recurrence after a mean time of 12.7
      months, following an initial interval of pain relief. There were no significant
      differences between patients with different grades of pain relief with respect to
      central doses. The mean time to the onset of pain relief was 3.6 weeks. The time
      to the onset of complete pain relief was significantly shorter than that for
      partial pain relief. Forty-nine patients reported mild-to-moderate facial
      numbness and one patient experienced paroxysmal temporalis muscle spasms two
      weeks after the treatment. GKRS treatment for medically refractory idiopathic TN
      with two isocenters resulted in an initial pain improvement in 95.6% of patients.
      The early response to the treatment might suggest a good outcome but, given the
      high incidence of nerve deficits, GKRS for TN with two isocenters is not
      recommended as a routine treatment protocol.

PMID- 22154203
TI  - Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma
      model.
AB  - CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, belotecan), a novel
      synthetic water-soluble camptothecin derivative, is known to have a significant
      anticancer effect in vitro on human glioma cell lines, including U87MG and
      U251MG. In the present study, we evaluated the in vivo antitumor effect of CKD
      602 in a mouse glioma model. Nude mice with established U87MG glioma were treated
      with a dose of CKD-602 of 0mg/kg (control group, injection with saline only;
      n=5), 40 mg/kg (group A) or 60 mg/kg (group B). Thereafter, the dose was repeated
      once every 4 days for a total of four doses. Tumor volume was measured
      histologically and apoptosis was detected using the terminal deoxynucleotide
      transferase dUTP nick end labeling (TUNEL) assay and immunofluorescence analysis
      with cleaved caspase-3. Mean tumor volume in each group was: control, 145.35
      mm(3); group A, 76.51 mm(3); group B, 73.99 mm(3)). Tumor volume was
      significantly smaller in both groups A and B compared with the control group
      (group A, p<0.01; group B, p<0.05). Apoptosis of tumor cells was evident to a
      greater extent in groups A and B relative to the control group, but there were no
      significant differences in tumor volume or apoptotic index between groups A and
      B. These results suggest that CKD-602 has a significant anticancer effect on
      glioma cells in vivo.

PMID- 22154204
TI  - Two patients with audiovestibular sarcoidosis.
AB  - We report two patients with biopsy-proven audiovestibular sarcoidosis who
      presented with hearing loss, vertigo and gait ataxia. Oto-neurological
      investigations confirmed the presence of sensorineural hearing loss, vestibular
      hypofunction and abnormal auditory brainstem responses. MRI scans of the brain
      revealed enhancement of the vestibulo-cochlear nerves. Both patients responded to
      high dose oral corticosteroid treatment, although one patient has required
      multiple trials of immunosuppressant drug therapy because of relapsing disease.

PMID- 22154205
TI  - Degradation of dichlorvos using hydrodynamic cavitation based treatment
      strategies.
AB  - The degradation of an aqueous solution of dichlorvos, a commonly used pesticide
      in India, has been systematically investigated using hydrodynamic cavitation
      reactor. All the experiments have been carried out using a 20 ppm solution of
      commercially available dichlorvos. The effect of important operating parameters
      such as inlet pressure (over a range 3-6 bar), temperature (31  degrees C, 36 
      degrees C and 39  degrees C) and pH (natural pH = 5.7 and acidic pH = 3) on the
      extent of degradation has been investigated initially. It has been observed that
      an optimum value of pressure gives maximum degradation whereas low temperature
      and pH of 3 are favorable. Intensification studies have been carried out using
      different additives such as hydrogen peroxide, carbon tetrachloride, and Fenton's
      reagent. Use of hydrogen peroxide and carbon tetrachloride resulted in the
      enhancement of the extent of degradation at optimized conditions but significant
      enhancement was obtained with the combined use of hydrodynamic cavitation and
      Fenton's chemistry. The maximum extent of degradation as obtained by using a
      combination of hydrodynamic cavitation and Fenton's chemistry was 91.5% in 1h of
      treatment time. The present work has conclusively established that hydrodynamic
      cavitation in combination with Fenton's chemistry can be effectively used for the
      degradation of dichlorvos.

PMID- 22154206
TI  - Transoral robotic surgery in head and neck cancer.
AB  - Robots have invaded industry and, more recently, the field of medicine. Following
      the development of various prototypes, Intuitive Surgical(r) has developed the Da
      Vinci surgical robot. This robot, designed for abdominal surgery, has been widely
      used in urology since 2000. The many advantages of this transoral robotic surgery
      (TORS) are described in this article. Its disadvantages are essentially its high
      cost and the absence of tactile feedback. The first feasibility studies in head
      and neck cancer, conducted in animals, dummies and cadavers, were performed in
      2005, followed by the first publications in patients in 2006. The first series
      including more than 20 patients treated by TORS demonstrated the feasibility for
      the following sites: oropharynx, supraglottic larynx and hypopharynx. However,
      these studies did not validate the oncological results of the TORS technique.
      TORS decreases the number of tracheotomies, and allows more rapid swallowing
      rehabilitation and a shorter length of hospital stay. Technical improvements are
      expected. Smaller, more ergonomic, new generation robots, therefore more adapted
      to the head and neck, will probably be available in the future.

PMID- 22154207
TI  - Acoustic phase shift: objective evidence for intralabyrinthine pressure
      disturbance in Meniere's disease provided by otoacoustic emissions.
AB  - OBJECTIVES: Still today, Meniere's disease (MD) can be definitively diagnosed
      only on post-mortem findings of endolymphatic hydrops. Otoacoustic emission (OAE)
      phase has been shown to be highly sensitive to intracranial pressure. Preliminary
      analysis of OAEs in MD patients indicated high sensitivity to slight variations
      in intracranial pressure. The principal objective of the present study was to
      confirm this specific sensitivity of OAEs in MD. PATIENTS AND METHODS: In a
      prospective study of 32 consecutive cases of acute MD seen in consultation or
      hospital, 20 patients (23 ears) underwent acoustic phase-shift test: i.e., seated
      vs. supine OAE phase centered around 1kHz, with results compared to controls.
      RESULTS: The acoustic phase-shift test was performed in 62.5% of acute patients
      (58.9% of affected ears). In the control group, the 95% confidence interval for
      phase shift was between -30 degrees  and +45 degrees . Phase shift was
      significantly elevated, beyond the normal interval, in 18 of the MD patients:
      range, -80 degrees  to +145 degrees . Sensitivity was 90%. Overall, in patients
      in whom transient evoked OAEs (TEOAEs) were present, positive predictive value
      was 100% and negative predictive value 92.3%. CONCLUSIONS: The acoustic phase
      shift test proved useful and powerful in demonstrating pressure imbalance in
      acute Meniere's disease.

PMID- 22154208
TI  - Non-invasive automated 3D thyroid lesion classification in ultrasound: a class of
      ThyroScanTM systems.
AB  - Ultrasound-based thyroid nodule characterization into benign and malignant types
      is limited by subjective interpretations. This paper presents a Computer Aided
      Diagnostic (CAD) technique that would present more objective and accurate
      classification and further would offer the physician a valuable second opinion.
      In this paradigm, we first extracted the features that quantify the local changes
      in the texture characteristics of the ultrasound off-line training images from
      both benign and malignant nodules. These features include: Fractal Dimension
      (FD), Local Binary Pattern (LBP), Fourier Spectrum Descriptor (FS), and Laws
      Texture Energy (LTE). The resulting feature vectors were used to build seven
      different classifiers: Support Vector Machine (SVM), Decision Tree (DT), Sugeno
      Fuzzy, Gaussian Mixture Model (GMM), K-Nearest Neighbor (KNN), Radial Basis
      Probabilistic Neural Network (RBPNN), and Naive Bayes Classifier (NBC).
      Subsequently, the feature vector-classifier combination that results in the
      maximum classification accuracy was used to predict the class of a new on-line
      test thyroid ultrasound image. Two data sets with 3D Contrast-Enhanced Ultrasound
      (CEUS) and 3D High Resolution Ultrasound (HRUS) images of 20 nodules (10 benign
      and 10 malignant) were used. Fine needle aspiration biopsy and histology results
      were used to confirm malignancy. Our results show that a combination of texture
      features coupled with SVM or Fuzzy classifiers resulted in 100% accuracy for the
      HRUS dataset, while GMM classifier resulted in 98.1% accuracy for the CEUS
      dataset. Finally, for each dataset, we have proposed a novel integrated index
      called Thyroid Malignancy Index (TMI) using the combination of FD, LBP, LTE
      texture features, to diagnose benign or malignant nodules. This index can help
      clinicians to make a more objective differentiation of benign/malignant thyroid
      lesions. We have compared and benchmarked the system with existing methods.

PMID- 22154209
TI  - Collaboration-based medical knowledge recommendation.
AB  - PURPOSE: Clinicians rely on a large amount of medical knowledge when performing
      clinical work. In clinical environment, clinical organizations must exploit
      effective methods of seeking and recommending appropriate medical knowledge in
      order to help clinicians perform their work. METHOD: Aiming at supporting medical
      knowledge search more accurately and realistically, this paper proposes a
      collaboration-based medical knowledge recommendation approach. In particular, the
      proposed approach generates clinician trust profile based on the measure of trust
      factors implicitly from clinicians' past rating behaviors on knowledge items. And
      then the generated clinician trust profile is incorporated into collaborative
      filtering techniques to improve the quality of medical knowledge recommendation,
      to solve the information-overload problem by suggesting knowledge items of
      interest to clinicians. RESULTS: Two case studies are conducted at Zhejiang
      Huzhou Central Hospital of China. One case study is about the drug recommendation
      hold in the endocrinology department of the hospital. The experimental dataset
      records 16 clinicians' drug prescribing tracks in six months. This case study
      shows a proof-of-concept of the proposed approach. The other case study addresses
      the problem of radiological computed tomography (CT)-scan report recommendation.
      In particular, 30 pieces of CT-scan examinational reports about cerebral
      hemorrhage patients are collected from electronic medical record systems of the
      hospital, and are evaluated and rated by 19 radiologists of the radiology
      department and 7 clinicians of the neurology department, respectively. This case
      study provides some confidence the proposed approach will scale up. CONCLUSION:
      The experimental results show that the proposed approach performs well in
      recommending medical knowledge items of interest to clinicians, which indicates
      that the proposed approach is feasible in clinical practice.

PMID- 22154210
TI  - Characterization and source apportionment of ambient air particulate matter
      (PM2.5) in Karachi.
AB  - Concentrations and source apportionment of PM(2.5) monitored at an urban
      residential site in Karachi Metropolitan, Pakistan have been reported in this
      paper. PM(2.5) aerosol samples were collected on alternative days (three times
      per week) for 24-hrs duration on Zefluor(TM) filter papers using Thermo-Electron
      Corporation Reference Ambient Air Sampler (RAAS). A total of 402 samples were
      collected from January 2006 to January 2008. According to results high PM(2.5)
      loads were observed in post monsoon months that is about 2 times than those
      observed in the summer and monsoon seasons in the yearlong measurements. The
      collected samples were analyzed using ICP-MS for trace metal concentration.
      Source apportionment was performed on PM samples using Positive Matrix
      Factorization (PMF) model. The results derived from PMF model indicated five (05)
      major contributors to PM(2.5) in Karachi which were: soil/road dust, industrial
      emissions, vehicular emissions, sea salt originated from Arabian Sea and
      secondary aerosols.

PMID- 22154211
TI  - A study of urban heat island and its association with particulate matter during
      winter months over Delhi.
AB  - Day and night time thermal mapping of Delhi has been done with MODIS satellite
      data for the months of November and December for years 2007, 2008, 2009 and 2010.
      The study reveals the formation of day time "cool island" over central parts of
      Delhi which are found to be cooler by a maximum of 4-6  degrees C than the
      surrounding rural areas. During the night time, however, the central parts of
      Delhi are found to be warmer by a maximum of 4-7  degrees C or even more than the
      surrounding rural areas thus confirming the formation of nocturnal urban heat
      island over Delhi. Measurements of solar spectral irradiance over Delhi reveal
      significantly lower values as compared to a rural site located south-west of
      Delhi, during the low wind conditions in the months of November and December.
      Analysis of average monthly temporal data of surface wind speed and particulate
      matter concentration over Delhi reveals a strong anti-correlation between wind
      speed and particulate matter concentration. High values of particulate matter
      during low wind conditions seem to favor the so called "cool island" over Delhi.
      Analysis of radiosonde data of 975 hPa and 850 hPa temperatures over Delhi during
      November and December from 1973 to 2010 reveals a warming trend at the 850 hPa
      level and an overall declining trend of ?T between 975 hPa temperatures and 850
      hPa temperatures, thus indicating a weakening of vertical thermal gradients over
      Delhi during these months. The study suggests that urban areas behave more like
      moderators of diurnal temperature variation in low wind conditions.

PMID- 22154212
TI  - Causes of toxicity to Hyalella azteca in a stormwater management facility
      receiving highway runoff and snowmelt. Part I: polycyclic aromatic hydrocarbons
      and metals.
AB  - The Terraview-Willowfield Stormwater Management Facility (TWSMF) receives inputs
      of multiple contaminants, including metals, polycyclic aromatic hydrocarbons
      (PAHs), road salt, and nutrients, via highway and residential runoff. Contaminant
      concentrations in runoff are seasonally dependent, and are typically high in
      early spring, coinciding with the snowmelt. In order to investigate the seasonal
      fluctuations of contaminant loading and related changes in toxicity to benthic
      invertebrates, overlying water and sediment samples were collected in the fall
      and spring, reflecting low and high contaminant loading, respectively, and four
      week sediment toxicity tests were conducted with Hyalella azteca. The effects of
      metals and PAHs are discussed here; the effects of salts, nutrients, and water
      quality are discussed in a companion paper. Survival and growth of Hyalella after
      exposure to fall samples were variable: survival was significantly reduced (64
      74% of controls) at three out of four sites, but there were no significant growth
      effects. More dramatic effects were observed after Hyalella were exposed to
      spring samples: survival was significantly reduced at the two sites furthest
      downstream (0-75% of controls), and growth was significantly lower in four out of
      five sites when comparing Hyalella exposed to site sediment with overlying site
      water versus site sediment with overlying control water. These seasonal changes
      in toxicity were not related to metals or PAHs: 1. levels of bioavailable metals
      were below those expected to cause toxicity, and 2. levels of PAHs in sediment
      were lowest at sites with the greatest toxicity and highest in water and sediment
      at sites with no toxicity. Although not associated with toxicity, some metals and
      PAHs exceeded probable and severe effect levels, and could be a cause for concern
      if contaminant bioavailability changes. Toxicity in the TWSMF appeared to be
      primarily associated with water-borne contaminants. The cause(s) of these effects
      are discussed in our companion manuscript.

PMID- 22154213
TI  - Influence of local factors in the relationship between mortality and heat waves:
      Castile-La Mancha (1975-2003).
AB  - INTRODUCTION: All the climate-change studies undertaken to date agree that one of
      the principal consequences of this phenomenon is the increase in heat waves,
      which, without exception, are linked to marked rises in mortality. The
      characteristics that modulate and determine the relationship between high
      temperatures and health must therefore be ascertained in the greatest possible
      detail, so that really effective prevention plans can be designed to address
      temperature extremes. METHODS: We examined the effect of heat waves on daily non
      accidental-cause mortality across all age groups in the Castile-La Mancha region
      (Spain) from 1975 to 2003. Quantitative analyses were performed using
      autoregressive integrated moving average (ARIMA) models, with other covariates,
      such as pressure trends, relative humidity, and duration and chronological number
      of heat waves. RESULTS: Mortality increased significantly with respect to the
      mean, when temperatures exceeded the designated provincial thresholds in Castile
      La Mancha. For each degree centigrade that temperatures exceeded these
      thresholds, the percentage increase in mortality amounted to increases of
      approximately 12% over the daily mean, albeit with clear provincial variations.
      The longest heat waves were associated with daily mortality, with those at the
      end of summer causing the lowest mortality. Meteorological situations most
      closely associated with increases in mortality were cyclonic conditions
      accompanied by low humidity. CONCLUSIONS: Spatio-temporal variability in the
      temperature-mortality relationship must be studied in order to enable really
      effective heat-wave prevention plans to be drawn up. The influence of variables,
      such as heat-wave duration or time of appearance, is important in the total
      increase in mortality during temperature extremes. Since parameters, such as
      humidity or pressure trends, can play very different roles in different
      geographical settings, they should be analysed separately from temperature.

PMID- 22154214
TI  - Causes of toxicity to Hyalella azteca in a stormwater management facility
      receiving highway runoff and snowmelt. Part II: salts, nutrients, and water
      quality.
AB  - The Terraview-Willowfield Stormwater Management Facility (TWSMF) features a
      tandem of stormwater management ponds, which receive inputs of multiple
      contaminants from highway and residential runoff. Previous research determined
      that benthic communities in the ponds were impacted by poor habitat quality, due
      to elevated sediment concentrations of metals and polycyclic aromatic
      hydrocarbons (PAHS), and salinity in the overlying water, but did not address
      seasonal changes, including those caused by the influx of contaminants with the
      snowmelt. In order to address this issue, water and sediment samples were
      collected from the TWSMF during the fall and spring, and four-week sediment
      toxicity tests were conducted with Hyalella azteca. The effects of metals and
      PAHs are discussed in a companion paper; the effects of road salt, nutrients, and
      water quality are discussed here. After exposure to fall samples, survival of
      Hyalella was reduced (64-74% of controls) at three out of four sites, but growth
      was not negatively affected. After exposure to spring samples, survival was 0-75%
      of controls at the two sites furthest downstream, and growth was significantly
      lower in four out of five sites when comparing Hyalella exposed to site water
      overlying site sediment versus control water overlying site sediment. Toxicity
      appeared to be related to chloride concentrations: little or no toxicity occurred
      in fall samples (200 mg Cl(-)/L), and significant effects on survival and growth
      occurred in spring samples above 1550 mg Cl(-)/L and 380 mg Cl(-)/L,
      respectively. Sodium chloride toxicity tests showed similar results: four-week
      LC50s and EC25s (growth) were 1200 and 420 mg Cl(-)/L, respectively. Although
      water quality and nutrients were associated with effects observed in the TWSMF,
      chloride from road salt was the primary cause of toxicity in this study. Chloride
      persists during much of the year at concentrations representing a significant
      threat to benthic communities in the TWSMF.

PMID- 22154215
TI  - Use of DGGE and COMPOCHIP for investigating bacterial communities of various
      vermicomposts produced from different wastes under dissimilar conditions.
AB  - This study describes the use of denaturing gradient gel electrophoresis (DGGE)
      and COMPOCHIP (i.e. a microarray targeting typical bacteria of stabilized organic
      materials and pathogenic bacteria) for investigating the bacterial communities of
      four different vermicomposts. These included a commercial vermicompost produced
      from cattle manure (CM) and three vermicomposts produced at pilot-scale by
      recycling: damaged tomato fruits (DT); olive-mill waste mixed with biosolids
      (OB); and winery wastes (WW). DGGE provided distinctive fingerprints of each
      vermicompost, which were statistically related to their particular chemical
      features. The comparison of the various vermicompost fingerprints showed that
      they contained bacterial communities with an average similarity coefficient of
      close to 80%. COMPOCHIP detected the presence of Sphingobacterium, Streptomyces,
      Alpha-Proteobacteria, Delta-Proteobacteria, and Firmicutes in all the
      vermicomposts. COMPOCHIP showed differences in the abundance of particular
      bacterial taxa among the vermicomposts, giving an idea about the usefulness of
      each vermicompost in the search for bacteria valuable to biotechnology. The joint
      use of DGGE and COMPOCHIP is a useful tool to compare vermicompost bacterial
      communities and to assess the potential of different vermicomposts as bioactive
      organic materials.

PMID- 22154216
TI  - TNF-alpha induced secretion of HMGB1 from non-immune canine mammary epithelial
      cells (MTH53A).
AB  - BACKGROUND: Mammary neoplasias are one of the most frequent and spontaneously
      occurring malignancies in dogs and humans. Due to the similar anatomy of the
      mammary gland in both species, the dog has become an important animal model for
      this cancer entity. In human breast carcinomas, the overexpression of a protein
      named high-mobility group box 1 (HMGB1) was reported. Cells of the immune system
      were described to release HMGB1 actively exerting cytokine function. Thereby it
      is involved in the immune system activation, tissue repair, and cell migration.
      Passive release of HMGB1 by necrotic cells at sites of tissue damage or in
      necrotic hypoxic regions of tumors induces cellular responses e.g. release of
      proinflammatory cytokines leading to elevated inflammatory response and neo
      vascularization of necrotic tumor areas. Herein we investigated if a time
      dependent stimulation with the separately applied proinflammatory cytokines TNF
      alpha and IFN-gamma can cause secretion of HMGB1 in a non-immune related HMGB1
      non-secreting epithelial canine mammary cell line (MTH53A) derived from non
      neoplastic tissue. METHODS: The canine cell line was transfected with recombinant
      HMGB1 bicistronic expression vectors and stimulated after transfection with the
      respective cytokine independently for 6, 24 and 48 h. HMGB1 protein detection was
      performed by Western blot analysis and quantified a by enzyme-linked
      immunosorbent assay. Live cell laser scanning multiphoton microscopy of MTH53A
      cells expressing a HMGB1-GFP fusion protein was performed in order to examine, if
      secretion of HMGB1 under cytokine stimulating conditions is also visible by
      fluorescence imaging. RESULTS: The observed HMGB1 release kinetics showed a
      clearly time-dependent manner with a peak release 24h after TNF-alpha
      stimulation, while stimulation with IFN-gamma had only small effects on the HMGB1
      release. Multiphoton HMGB1 live cell microscopy showed diffuse cell membrane
      structure changes 29 h after cytokine-stimulation but no clear secretion of HMGB1
      GFP after TNF-alpha stimulation was visible. CONCLUSION: Our results demonstrate
      that non-immune HMGB1-non-secreting cells of epithelial origin derived from
      mammary non-neoplastic tissue can be induced to release HMGB1 by single cytokine
      application. This indicates that tumor and surrounding tissue can be stimulated
      by tumor present inflammatory and necrotic cytokines to release HMGB1 acting as
      neo-vascularizing factor thus promoting tumor growth.

PMID- 22154217
TI  - Effects of overweight and obesity on walking characteristics in adolescents.
AB  - Child and adolescent obesity is growing at a staggering rate. Associated
      potential health risks have been acknowledged in the adult population, and
      similar concerns have been raised for children and adolescents. However,
      distinguishing locomotor characteristics related to obesity have yet to be
      clearly identified for adolescents. The aims of the study were to examine the
      effects of walking velocity and gender on spatio-temporal characteristics of gait
      between normal weight (NW) and overweight and obese (OWO) adolescents. In
      addition, we sought to identify characteristics of gait that are related to body
      mass index percentile (BMI%). Adolescent students in grades 7-10 (N=111) from a
      charter school participated in the study. All participants walked at two speeds
      (preferred, fast) over an instrumented walkway (120 Hz). Spatio-temporal
      characteristics of gait were extracted from four walkway passes and evaluated.
      Results identified significant (p<.05) differences in velocity, percent double
      support, percent swing phase, and stance width between groups. Only stance width
      was different (p<.05) between genders. Models to predict BMI% from kinematic
      walking parameters were of moderate strength (averaging 43.5% explained variance)
      and were generally stronger for females versus males. Percent double support was
      the primary predictor variable of BMI% across speed and gender. It is suggested
      that OWO adolescents may be challenged with control of movement of the center of
      mass during the support phase of walking.

PMID- 22154218
TI  - One failed clinical trial (of 5HT3 antagonists) does not invalidate the concept.

PMID- 22154219
TI  - Double spikes to single electrical stimulation correlates to spontaneous activity
      of nociceptors in painful neuropathy patients.
AB  - Multiple firing of C nociceptors upon a single electrical stimulus has been
      suggested to be a possible mechanism contributing to neuropathic pain. Because
      this phenomenon maybe based on a unidirectional conduction block, it might also
      be related to neuropathic changes without a direct link to pain. We investigated
      painful neuropathy patients using microneurography and analysed nociceptors for
      the occurrence of multiple spiking and spontaneous activity. In 11 of 105
      nociceptors, double spiking was found, with 1 fibre even showing triple spikes on
      electrical stimulation. The interval between the main action potential and the
      multiple spikes ranged from 13 to 100 ms. There was a significant association
      between spontaneous activity and multiple spiking in C nociceptors, with
      spontaneous activity being present in 9 of 11 fibres with multiple spiking, but
      only in 21 of 94 nociceptors without multiple spiking (P<.005, Fisher exact
      test). Among the 75 C nociceptors without spontaneous activity, only 2
      nociceptors showed multiple spiking. In 8 neuropathy patients without pain,
      double spiking was found only in 4 of 90 nociceptors. Multiple spiking of
      nociceptors coincides with spontaneous activity in nociceptors of painful
      neuropathy patients. We therefore conclude that rather than being a generic sign
      of neuropathy, multiple spiking is linked to axonal hyperexcitability and
      spontaneous activity of nociceptors. It is still unclear whether it also is
      mechanistically related to the clinical pain level.

PMID- 22154220
TI  - Recent advances in single-cell studies of gene regulation.
AB  - A mechanistic understanding of gene regulatory network dynamics requires
      quantitative single-cell data of multiple network components in response to well
      defined perturbations. Recent advances in the development of fluorescent
      biomarkers for proteins, detection of RNA and interactions, microfluidic
      technology, and high-resolution imaging have set the stage for a host of new
      studies that elucidate the important roles of stochasticity and cell-cell
      variability in response to external perturbations. In this review, we briefly
      describe methods for high-resolution visualization and the control of gene
      expression, along with application of these novel methods to recent studies
      involving gene networks.

PMID- 22154222
TI  - The effects of TNF-alpha blocking therapy on lipid levels in rheumatoid
      arthritis: a meta-analysis.

PMID- 22154221
TI  - Korean Observational Study Network for Arthritis (KORONA): establishment of a
      prospective multicenter cohort for rheumatoid arthritis in South Korea.
AB  - OBJECTIVES: The object of this study was to introduce the KORean Observational
      study Network for Arthritis (KORONA) registry with an emphasis on the design of
      the Korean rheumatoid arthritis (RA) national database, as well as to provide an
      overview of the RA patients who are currently registered in KORONA. METHODS: The
      KORONA was established in July 2009 by the Clinical Research Center for
      Rheumatoid Arthritis (CRCRA) in South Korea. KORONA is based on a prospective
      protocol and standard, defined data collection instruments. Demographic and
      clinical features, laboratory and radiologic data, health-related outcomes,
      treatment side effects, resource utilization, and health behaviors of the RA
      cohort patients are recorded in a database. RESULTS: A total of 23 institutions,
      which are about 38% of the rheumatologic departments at tertiary academic
      hospitals across South Korea, are part of KORONA. The quality control of data
      collection and management has been performed through annual monitoring and
      auditing, staff training, and providing standard operation protocol by the
      executive committee of CRCRA. As of 31 December 2010, 4721 patients with
      established RA were included in KORONA, because an annual survey had started to
      be performed in July 2010. CONCLUSIONS: KORONA is the first nationwide Korean RA
      specific cohort and it will provide valuable "real-world" information for Korean
      RA patients.

PMID- 22154223
TI  - Effect of anterior strut chordal transection on the force distribution on the
      marginal chordae of the mitral valve.
AB  - OBJECTIVES: Transection of the secondary chordae on the anterior leaflet of the
      mitral valve to relieve leaflet tethering and reduce regurgitation is an
      experimentally proven procedure to correct functional mitral regurgitation. In
      the present study, we sought to investigate whether transecting the secondary
      chordae would have an effect on the marginal chordal force on the same leaflet.
      METHODS: Adult porcine mitral valves (n = 8) were studied in a pulsatile heart
      simulator, in which the papillary muscle positions can be precisely positioned.
      Miniature transducers were inserted into the anterior marginal chordae to measure
      the chordal forces. Each valve was studied under baseline conditions, 3 different
      tethering conditions (apical, apical-lateral, and apical-lateral-posterior), and
      after chordal cutting in the 3 tethering conditions. The temporal changes and
      peak and average marginal chordal forces under each condition are reported.
      RESULTS: Apical tethering increased the marginal chordal force by an average of
      96% but remained unchanged after chordal cutting. With apical-lateral tethering,
      the marginal chordal force increased by 210% from baseline and increased further
      to 350% of baseline after chordal cutting. After apical-lateral-posterior
      tethering, the marginal chordal force increased to 335% of baseline before
      transection and by 548% after transection. CONCLUSIONS: The increase in the
      marginal chordal force after secondary chordal cutting depends on the location of
      the papillary muscles and the extent of leaflet tethering. Although chordal
      cutting might not alter the valve mechanics under minimal leaflet tethering, it
      significantly affects the mechanics when the leaflet tethering is more
      pronounced, which is typically seen in patients with functional mitral
      regurgitation.

PMID- 22154224
TI  - Ursodeoxycholic acid with vitamin E in patients with nonalcoholic
      steatohepatitis: long-term results.
AB  - BACKGROUND: The combination of ursodeoxycholic acid (UDCA) and vitamin E is a
      therapeutic option for nonalcoholic steatohepatitis (NASH) but randomized
      controlled studies have produced inconsistent results. The objective of this
      study was to report the long-term tolerability and efficacy of this combination
      in our ten-year single center experience. METHODS: The study group included 101
      adult patients with persistent elevation of serum aminotransferases (AST and ALT)
      and/or gamma glutamyl-transferase (GGT), in whom a histological diagnosis of NASH
      was made from January 1998 to January 2009, and who were treated with a
      combination of UDCA with vitamin E. RESULTS: Median body mass index (30 kg/m(2))
      remained unchanged during the study. UDCA and vitamin E were well tolerated (5%
      withdrawal for side effects). Mean serum AST, ALT and GGT levels (expressed as
      times of Upper Normal Limit) diminished significantly (1.39 +/- 0.74 to 0.78 +/-
      0.34 for AST, 1.72 +/- 0.92 to 0.91 +/- 0.69 for AST and 3.25 +/- 2.85 to 1.30 +/
      1.30 for GGT). AST, ALT and GGT reached normal range in 80%, 70% and 65% of the
      patients, respectively. From the ten patients who had a second liver biopsy
      during follow-up, NAS score improved in seven, and worsened in one. CONCLUSIONS:
      The combination of UDCA with vitamin E significantly improves liver function
      tests in long-term and is very well tolerated.

PMID- 22154225
TI  - Ro52 autoantibody-positive women's experience of being pregnant and giving birth
      to a child with congenital heart block.
AB  - OBJECTIVE: congenital heart block may develop in the fetus of women with Ro/SSA
      autoantibodies. The aim of this study was to investigate how women expecting a
      child with congenital heart block (CHB) experienced their pregnancy and post
      partum period. DESIGN, SETTING AND PARTICIPANTS: women giving birth to a child
      with CHB in Sweden during 2000-2009 were identified in a population-based manner
      and individually interviewed post-pregnancy using a semi-structured interview
      guide. The interviews (n=21) were audiotaped, transcribed verbatim and analysed
      by qualitative content analysis. FINDINGS: three categories emerged from the
      responses: learning, suspense and facing. Learning contained both learning about
      the child's heart block, but frequently also about autoantibody-positivity and a
      potential rheumatic diagnosis in the mother (16/21). The medical procedures and
      information differed considerably depending on the area of residence and who was
      encountered in the health-care system. In many cases, ignorance about this rare
      condition caused a delay in treatment and surveillance. Suspense described the
      women's struggle to cope with the feeling of guilt and that the child had a
      serious heart condition and might not survive the pregnancy. Facing included the
      post-partum period, leaving the hospital and adjusting to everyday life. The
      women had tended to put their pregnancies 'on hold', and some described that they
      needed prolonged time to bond with their newborn child. CONCLUSION: increased
      awareness and knowledge of CHB are needed to provide adequate care. Offering
      psychological support by a health-care professional to facilitate early bonding
      with the child should be considered. IMPLICATIONS FOR PRACTICE: there is a need
      for structured programs for surveillance of the pregnancies. Such programme
      should implement guidelines for the involved personnel in the chain of care and
      make relevant information accessible for the women and families.

PMID- 22154226
TI  - [Kounis syndrome].
AB  - Kounis syndrome was described in 1991 by Kounis and Zavras as the coincidental
      occurrence of acute coronary syndromes with allergic reactions (anaphylactic or
      anaphylactoid). Today, allergic angina and allergic myocardial infarction are
      referred to as Kounis syndrome, and the latter has been reported in association
      with a variety of drugs, insect stings, food, environmental exposures and medical
      conditions, among other factors. The incidence is not known, as most of the
      available information comes from case reports or small case series. In this
      article, the clinical aspects, diagnosis, pathogenesis, related conditions and
      therapeutic management of the syndrome are discussed.

PMID- 22154227
TI  - [Malignant neuroleptic syndrome and Clostridium difficile: causal association or
      mere coincidence?].

PMID- 22154228
TI  - Human papillomavirus deoxyribonucleic acid testing in developed countries.
AB  - Cervical cancer has been largely eliminated in developed countries with the
      implementation of cytology-based screening programmes that depend on a call
      recall system, followed by colposcopy and biopsy, treatment of precancerous
      lesions and follow up. With the discovery that persistent infection with high
      risk human papillomavirus types is necessary for the development of cervical
      cancer, several tests for human papillomavirus deoxyribonucleic acid have been
      developed that can identify women at risk. Human papillomavirus deoxyribonucleic
      acid testing is more sensitive and only slightly less specific than cytology for
      detecting cervical intraepithelial neoplasia. It is also more reproducible, with
      the potential for self-sampling. Human papillomavirus genotyping, messenger RNA
      analysis and other biomarkers can help to further stratify this group and
      diminish referrals to colposcopy. Initially, human papillomavirus testing was
      used as an adjunct to cytology for triage of borderline cases, but evidence has
      shown its superiority as a screening method and in the follow up of women treated
      for cervical intraepithelial neoplasia.

PMID- 22154229
TI  - Cardiac biomarkers in equine medicine.

PMID- 22154230
TI  - MultiBac: expanding the research toolbox for multiprotein complexes.
AB  - Protein complexes composed of many subunits carry out most essential processes in
      cells and, therefore, have become the focus of intense research. However,
      deciphering the structure and function of these multiprotein assemblies imposes
      the challenging task of producing them in sufficient quality and quantity. To
      overcome this bottleneck, powerful recombinant expression technologies are being
      developed. In this review, we describe the use of one of these technologies,
      MultiBac, a baculovirus expression vector system that is particularly tailored
      for the production of eukaryotic multiprotein complexes. Among other
      applications, MultiBac has been used to produce many important proteins and their
      complexes for their structural characterization, revealing fundamental cellular
      mechanisms.

PMID- 22154231
TI  - Intrinsic disorder: signaling via highly specific but short-lived association.
AB  - Association between signaling proteins and their cellular targets is generally
      thought to be highly specific (implicating a high association constant, K(a))
      and, at the same time, transient or short-lived (corresponding to a high
      dissociation rate constant, k(d)). However, a combination of high K(a) and high
      k(d) would lead to a high association rate constant (k(a) = K(a)k(d)), which
      poses a problem because there is a limit to which k(a) can be increased, set by
      the diffusional approach to form the complex. In this Opinion article, I propose
      that having the signaling protein disordered before binding to the target
      provides a way out of this quandary. The intrinsic disorder of the signaling
      protein would decrease K(a) without sacrificing the specificity of the complex,
      and thus would allow k(d) to be increased to a range appropriate for signaling.

PMID- 22154232
TI  - The importance of patient-centred imaging.

PMID- 22154233
TI  - An international environmental scan of quality indicators for cardiovascular
      care.
AB  - Quality indicators (QIs) are increasingly being used to measure and improve the
      quality of cardiac care. We conducted an international environmental scan to
      identify and critically appraise published QI development initiatives addressing
      cardiovascular disease (CVD). A review of the peer-reviewed and grey English
      language literature was conducted to identify published CVD QI development
      initiatives. The quality of identified studies was assessed using a modified
      version of the Appraisal of Guidelines for Research and Evaluation (AGREE) II QI
      tool-an instrument originally developed for the assessment of the quality of
      clinical practice guidelines. An initial literature search identified 2314
      potentially relevant abstracts of peer-reviewed articles. After a review of the
      abstracts, 120 full text articles were retrieved and reviewed. Of these, 20
      articles and 1 peer-reviewed monograph were selected for critical appraisal (n =
      21). Most of the initiatives were conducted in North America (76%) and were
      published after 2005 (62%). The majority (5 of 6) of the AGREE II QI domain
      scores were skewed toward higher values, including the median score for the
      'overall quality' rating (83.3%). Of the CVD categories addressed within the 21
      initiatives, heart failure was the most common (n = 10 QI indicator sets),
      followed by acute coronary syndromes (n = 8). Considerable variation was observed
      in the methods utilized and the degree of scientific rigour applied in the
      published international CVD QI development initiatives. Adoption of standardized
      methods could help improve the quality of QI development initiatives.

PMID- 22154234
TI  - Managing chronic myeloid leukemia: a coordinated team care perspective.
AB  - Treatment of chronic myeloid leukemia (CML) has seen dramatic progress in recent
      years with the development of tyrosine kinase inhibitors (TKIs). To take maximum
      advantage of therapy with TKIs, compliance and good understanding of monitoring
      response to therapy are essential. We established a team that included a
      hematologist, a physician assistant (PA), and a nurse who work closely with a
      social worker, a pharmacist, and a research coordinator to assist patients
      throughout their journey with CML. The patient and the referring community
      oncologist were incorporated into this team. This coordinated team care approach
      takes advantage of each member's specific skills to provide patients with
      education about CML, encourage patients' strong involvement in
      tracking/monitoring results/response to therapy, and support patients with issues
      that arise throughout the long course of the disease. A low rate of noncompliance
      with clinic visits (3%) was an indirect measure of the impact of this approach.
      The inclusion of the referring oncologist in the team extended the tracking of
      monitoring results to the community practice. We conclude that a coordinated team
      care approach is feasible in the management of patients with CML. This approach
      provided patients with education and a good understanding of response to therapy
      and improved relations with the health care team.

PMID- 22154235
TI  - Examining the influence of the Enforcing Underage Drinking Laws (EUDL) program on
      alcohol-related outcomes in five communities surrounding Air Force bases.
AB  - In 2006, the Office of Juvenile Justice and Delinquency Prevention (OJJDP)
      awarded discretionary grants to five communities as part of the Enforcing
      Underage Drinking Laws (EUDL) initiative to implement an environmental strategy
      approach to reduce drinking and associated misconducts among Air Force members.
      The evaluation design was a within-site, pre-test/post-test intervention
      comparison of baseline data to out-year data. Four of the five communities had
      significant decreases in one or more of the outcomes of interest from pre-test to
      post-test. Two communities (Great Falls, MT and Tucson, AZ) had a significant
      decline in the compliance check failure rate of local establishments that sell
      alcohol. One community (Great Falls, MT) had a significant decline in arrests for
      possession of alcohol by a minor. Four communities (Great Falls, MT; Tucson, AZ;
      Phoenix, AZ; Honolulu, HI) had a significant decline in DUI/DWI arrests. These
      findings build on results reported in an earlier article which provided evidence
      to suggest that the EUDL program had an influence on self-reported drinking
      behaviors in three of the five communities. These two articles, in combination,
      provide evidence to suggest for the first time that community-level programs
      using an environmental strategy approach can be successful in targeting military
      members.

PMID- 22154236
TI  - Daily marijuana use and suicidality: the unique impact of social anxiety.
AB  - Despite a clear relationship between marijuana use and suicidality, little is
      known about psychological vulnerability factors that may interact with marijuana
      use to increase suicidality among this high-risk group. The present study
      examined the moderational impact of social anxiety on the relationship between
      marijuana use status (current users vs abstainers) and suicidality among 343
      community adults. We also examined whether social anxiety moderated the relation
      between more frequent use (daily vs less frequent) among the 134 current
      marijuana users. Although social anxiety did not moderate the relation between
      use status and suicidality, it did moderate the relation between daily use status
      and suicidality after controlling for a wide range of relevant variables (e.g.,
      demographics, depression, negative affect, and other types of anxiety). The
      overall model accounted for 59% of the variance in suicidality such that daily
      marijuana users with elevated social anxiety reported the highest suicidality.
      Findings highlight the importance of considering social anxiety in efforts to
      understand and prevent suicidality among this high-risk population.

PMID- 22154238
TI  - Feature selection from nocturnal oximetry using genetic algorithms to assist in
      obstructive sleep apnoea diagnosis.
AB  - Nocturnal pulse oximetry (NPO) has demonstrated to be a powerful tool to help in
      obstructive sleep apnoea (OSA) detection. However, additional analysis is needed
      to use NPO alone as an alternative to nocturnal polysomnography (NPSG), which is
      the gold standard for a definitive diagnosis. In the present study, we
      exhaustively analysed a database of blood oxygen saturation (SpO(2)) recordings
      (80 OSA-negative and 160 OSA-positive) to obtain further knowledge on the
      usefulness of NPO. Population set was randomly divided into training and test
      sets. A feature extraction stage was carried out: 16 features (time and frequency
      statistics and spectral and nonlinear features) were computed. A genetic
      algorithm (GA) approach was applied in the feature selection stage. Our
      methodology achieved 87.5% accuracy (90.6% sensitivity and 81.3% specificity) in
      the test set using a logistic regression (LR) classifier with a reduced number of
      complementary features (3 time domain statistics, 1 frequency domain statistic, 1
      conventional spectral feature and 1 nonlinear feature) automatically selected by
      means of GAs. Our results improved diagnostic performance achieved with
      conventional oximetric indexes commonly used by physicians. We concluded that GAs
      could be an effective and robust tool to search for essential oximetric features
      that could enhance NPO in the context of OSA diagnosis.

PMID- 22154237
TI  - Evaluation of the anti-arenaviral activity of the subtilisin kexin isozyme-1/site
      1 protease inhibitor PF-429242.
AB  - The cellular protease subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is
      implicated in the proteolytic processing of the viral envelope glycoprotein
      precursor (GPC) of arenaviruses, a step strictly required for production of
      infectious progeny. The small molecule SKI-1/S1P inhibitor PF-429242 was shown to
      have anti-viral activity against Old World arenaviruses. Here we extended these
      studies and show that PF-429242 also inhibits GPC processing and productive
      infection of New World arenaviruses, making PF-429242 a broadly active anti
      arenaviral drug. In combination therapy, PF-429242 potentiated the anti-viral
      activity of ribavirin, indicating a synergism between the two drugs. A hallmark
      of arenaviruses is their ability to establish persistent infection in vitro and
      in vivo. Notably, PF-429242 was able to efficiently and rapidly clear persistent
      infection by arenaviruses. Interruption of drug treatment did not result in re
      emergence of infection, indicating that PF-429242 treatment leads to virus
      extinction.

PMID- 22154239
TI  - The fate of indigenous microbiota, starter cultures, Escherichia coli, Listeria
      innocua and Staphylococcus aureus in Danish raw milk and cheeses determined by
      pyrosequencing and quantitative real time (qRT)-PCR.
AB  - The purpose of this work was to study the bacterial communities in raw milk and
      in Danish raw milk cheeses using pyrosequencing of tagged amplicons of the V3 and
      V4 regions of the 16S rDNA and cDNA. Furthermore, the effects of acidification
      and ripening starter cultures, cooking temperatures and rate of acidification on
      survival of added Escherichia coli, Listeria innocua and Staphylococcus aureus in
      cheeses at different stages of ripening were studied by pyrosequencing and
      quantitative real time (qRT)-PCR. A high diversity of bacterial species was
      detected in raw milk. Lactococcus lactis, Streptococcus thermophilus,
      Lactobacillus casei and Lactobacillus rhamnosus were the main bacteria detected
      in raw milk and cheeses. Bacteria belonging to the genera Brevibacterium,
      Staphylococcus, Escherichia, Weissella, Leuconostoc, Pediococcus were also
      detected in both 16S rDNA and cDNA obtained from raw milk and cheeses. E. coli,
      which was added to milk used for production of some cheeses, was detected in both
      DNA and RNA extracted from cheeses at different stages of ripening showing the
      highest percentage of the total sequence reads at 7 days of ripening and
      decreased again in the later ripening stages. Growth of E. coli in cheeses
      appeared to be affected by the cooking temperature and the rate of acidification
      but not by the ripening starter cultures applied or the indigenous microbiota of
      raw milk. Growth of L. innocua and S. aureus added to milks was inhibited in all
      cheeses at different stages of ripening. The use of 16S rRNA gene pyrosequencing
      and qRT-PCR allows a deeper understanding of the behavior of indigenous
      microbiota, starter cultures and pathogenic bacteria in raw milk and cheeses.

PMID- 22154240
TI  - Clustering of venous thrombosis events at the start of tamoxifen therapy in
      breast cancer: a population-based experience.
AB  - INTRODUCTION: The epidemiology of tamoxifen and venous thromboembolism (VTE) is
      not well understood, and most data on tamoxifen toxicity are from adjuvant
      clinical trials. This study examined the relationship between the duration of
      tamoxifen use in female patients with breast cancer and the risk of VTE in a
      large population-based setting. MATERIALS AND METHODS: Retrospective electronic
      data extraction on tamoxifen utilization was undertaken among a cohort of 3572
      women with breast cancer seen at Marshfield Clinic between January 1, 1994 and
      June 31, 2009. Observational follow-up extended until February, 2010. RESULTS: On
      initial exposure to tamoxifen, women had a clustering of VTE events. Cox
      proportional hazards regression, adjusting for multiple clinically-important
      covariates including age, body mass index, cancer stage, and concurrent diabetes,
      demonstrated that as use of tamoxifen continued in those without earlier VTE
      events, risk of subsequent VTE gradually increased, albeit at a lower rate
      (hazard ratio per year of tamoxifen duration=1.225, P <0.0001). CONCLUSIONS: In
      our study population, initiating tamoxifen coincided with an initial clustering
      of VTE events, with risks due specifically to tamoxifen, increasing during
      continued exposure. Evidence suggested that the VTE clustering occurred in high
      risk individuals at initiation of tamoxifen therapy. Careful selection of
      patients for whom tamoxifen therapy is appropriate based on susceptibility to VTE
      is thus required prior to initiation of therapy.

PMID- 22154241
TI  - Lack of evidence for association between factor XIII-A Val34Leu polymorphism and
      ischemic stroke: a meta-analysis of 8,800 subjects.
AB  - INTRODUCTION: Epidemiological studies have evaluated the association between
      factor XIII-A (FXIII-A) Val34Leu polymorphism and risk of ischemic stroke, but
      the results remain inconclusive. This meta-analysis was therefore designed to
      clarify these controversies. METHODS: Systematic searches of electronic databases
      Embase, PubMed and Web of Science, as well as hand searching of the references of
      identified articles and the meeting abstracts were performed. Study selection,
      data abstraction and study quality evaluation (using the Newcastle-Ottawa Scale,
      NOS) were independently conducted in duplicate. Statistical analyses were
      performed using software Review Manager (Version 5.1.2) and Stata (Version 11.0).
      The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were
      performed. Fixed or random effects model was separately used depending on the
      heterogeneity between studies. Publication bias was tested by funnel plot,
      Egger's regression test and Begg's test. Sensitivity analysis was conducted by
      limiting the meta-analysis to the high quality studies (NOS score>=8). RESULTS: A
      total of 16 studies including 3,807 cases and 4,993 controls were combined
      showing no evidence of association between FXIII-A Val34Leu polymorphism and
      ischemic stroke (for Val/Leu vs. Val/Val : OR=0.95, 95%CI=0.77-1.16; for Leu/Leu
      vs. Val/Val: OR=0.90, 95%CI=0.73-1.11; for dominant model: OR=0.97, 95%CI=0.81
      1.17; for recessive model: OR=0.95, 95%CI=0.77-1.17). In the subgroup analyses by
      study design, ethnicity and specific subtypes (small-vessel occlusive ischemic
      stroke and large-artery atherosclerotic ischemic stroke ), there was lack of
      evidence for the association. CONCLUSIONS: This meta-analysis indicates that
      there is no evidence for association between factor XIII-A Val34Leu polymorphism
      and ischemic stroke.

PMID- 22154242
TI  - Influence of cytochrome 2C19 allelic variants on on-treatment platelet reactivity
      evaluated by five different platelet function tests.
AB  - BACKGROUND: The antiplatelet effect of clopidogrel has been linked to cytochrome
      P450 2C19 (CYP2C19) carrier status. The presence of loss of function and gain of
      function variants were found to have a gene-dose effect on clopidogrel
      metabolism. However, genotyping is only one aspect of predicting response to
      clopidogrel and several platelet function tests are available to measure platelet
      response. Patients and methods We studied the influence of CYP2C19 allelic
      variants on on-treatment platelet reactivity as assessed by light transmission
      aggregometry (LTA), the VerifyNow P2Y12 assay, the VASP assay, multiple electrode
      aggregometry (MEA), and the Impact-R in 288 patients after stenting for
      cardiovascular disease. Allelic variants of CYP2C19 were determined with the
      Infiniti(r) CYP450 2C19+ assay and categorized into four metabolizer states
      (ultrarapid, extensive, intermediate, poor). RESULTS: Platelet reactivity
      increased linearly from ultrarapid to poor metabolizers using the VerifyNow P2Y12
      assay (P = 0.04), the VASP assay (P = 0.02) and the Impact-R (P = 0.04). The
      proportion of patients with high on-treatment residual platelet reactivity (HRPR)
      identified by LTA, the VerifyNow P2Y12 assay and the VASP assay increased when
      the metabolizer status decreased, while no such relationship could be identified
      for results of MEA and Impact-R. The presence of loss of function variants
      (*2/*2, *2-8*/wt, *2/*17) was an independent predictor of HRPR in LTA and the
      VASP assay while it did not reach statistical significance in the VerifyNow P2Y12
      assay, MEA, and the Impact-R. CONCLUSION: Depending on the type of platelet
      function test differences in the association of on-treatment platelet reactivity
      with CYP2C19 carrier status are observed.

PMID- 22154243
TI  - The APC-PCI concentration as an early marker of activation of blood coagulation:
      a study of women on combined oral contraceptives.
AB  - BACKGROUND: The risk of venous tromboembolism (VTE) in women taking combined oral
      contraceptives (COCs) is attributed to changes in coagulation and fibrinolysis.
      The impact of the COCs may be greater in women with preexisting thrombophilic
      defects. Nevertheless most women who suffer from venous thrombosis do not have
      any of the well known hereditary or acquired risk factors. A simple and sensitive
      marker of"thrombogenicity" has not been identified. OBJECTIVES: To investigate
      the effects of two different monophasic combined oral contraceptives (COCs) on
      the plasma concentrations of activated protein C-inhibitor of protein C ( APC
      PCI) and on comparable hemostatic factors in fertile women. METHOD: Forty four
      healthy nulliparous women with regular menstrual periods were included and
      randomly assigned to start with a monophasic preparation containing 30MUg
      ethinylestradiol and 150MUg levonogestrel (LNG/EE) or a preparation containing
      30MUg ethinylestradiol and 150 ug desogestrel (DG/EE). After a wash out period of
      two months, treatment with the alternate preparation was initiated and continued
      for two more cycles. RESULTS: The plasma concentration of the APC-PCI complex and
      thrombin-antithrombin complex (TAT) increased during treatment with the two COCs.
      During DG/EE treatment the APC-PCI complex increased significantly more than
      during LNG/EE (p<0,01).The plasma concentration of D-dimer did not increase
      during OC treatment. CONCLUSION: The APC-PCI complex concentration, which serves
      as a marker for thrombin generation and indicates hypercoagulability, was
      increased during COC treatment compared to baseline. The method is a sufficiently
      sensitive marker to detect even small differences in the activation of
      coagulation.

PMID- 22154244
TI  - From candidate gene to genome-wide association studies in cardiovascular disease.
AB  - Continuous updating of the genotyping technology has led to improvement of
      genetic study design. The recent advances in technology coupled with the advances
      in our understanding of the molecular mechanisms have allowed a more
      comprehensive examination of the role of genetics, environment and their
      interaction in determining the individual risk of cardiovascular disease (CVD).
      Initial candidate gene studies identified a limited number of polymorphisms
      associated with disease, explaining only a minor part of trait variance.
      Furthermore, results were not often concordant, with meta-analyses not reaching
      the statistical power to confirm an association in many cases. The advent of the
      genome-wide design furnished an enormous quantity of information and decreased
      time of genotyping, while increased complexity of analyses and costs. Their
      results were more concordant, even when they suggested associations between CVD
      and polymorphisms distant from codifying regions or in genes involved in
      previously unsuspected pathways. Future results from genome-wide studies coupled
      with results from functional studies and investigation on gene-environment
      interactions will allow improvement of cardiovascular risk assessment and
      discovery of new targets for therapy and prevention. In this review, a brief
      history of cardiovascular genetics is reported, from candidate gene to genome
      wide association studies, that led to the identification of association between
      CVD and SNPs in the 9p21 region, firstly thought a gene desert without
      importance.

PMID- 22154245
TI  - Detection of a procoagulable state during controlled ovarian hyperstimulation for
      in vitro fertilization with global assays of haemostasis.
AB  - INTRODUCTION: Controlled ovarian hyperstimulation during in vitro fertilization
      (IVF) causes profound increments in serum estradiol which may influence
      haemostasis and the ovarian hyperstimulation syndrome. In the present study we
      investigated the effect of the standard IVF-stimulation protocol on coagulation
      and fibrinolysis as assessed by different global haemostatic assays. MATERIALS
      AND METHODS: Blood samples were drawn from 31 women during the down-regulation
      phase when estradiol secretion is inhibited, and before egg retrieval, i.e. when
      estradiol levels are at supraphysiological levels, in the following called high
      level stimulation phase. Haemostasis was assessed during both treatment phases
      with 1) the calibrated automated thrombogram which measures thrombin generation,
      2) overall haemostasis potential which measures fibrin formation and degradation
      and 3) fibrin gel permeability measurements which measures the quality of the
      fibrin network. RESULTS: Estradiol increased from <150pg/mL to 5889pg/mL (range
      1620-19500pg/mL). We found both increased thrombin generation as measured by the
      calibrated automated thrombogram (p<0.001) and an increase in overall haemostasis
      potential (p<0.001) from time of down-regulation to high level stimulation.
      CONCLUSIONS: The assays used indicated procoagulable changes in haemostasis
      during in vitro fertilization. Further studies should evaluate their potential in
      the prediction of thrombosis and hyperstimulation.

PMID- 22154246
TI  - The protein C pathway and sepsis.
AB  - After the discovery of the key components of the protein C (PC) pathway a
      beneficial effect on survival of the infusion of activated protein C (APC) in
      animal models of sepsis was demonstrated, leading to the development of
      recombinant human activated protein C (rh-APC) as a therapeutic agent. It soon
      became clear that rather than the anticoagulant and profibrinolytic activities of
      APC, its anti-inflammatory and cytoprotective properties played a major role in
      the treatment of patients with severe sepsis. Such properties affect the response
      to inflammation of endothelial cells and leukocytes and are exerted through
      binding of APC to at least five receptors with intracellular signaling. The main
      APC protective mechanism involves binding of the Gla-domain to the endothelial
      protein C receptor (EPCR) and cleavage of protease activated receptor 1 (PAR-1),
      eliciting suppression of proinflammatory cytokines synthesis and of intracellular
      proapoptotic pathways and activation of endothelial barrier properties. However,
      thrombin cleaves PAR-1 with much higher catalytic efficiency, followed by pro
      inflammatory, pro-apoptotic and barrier disruptive intracellular signaling, and
      it is unclear how APC can exert a protective activity through the cleavage of PAR
      1 when thrombin is also present in the same environment. Interestingly, in
      endothelial cell cultures, PAR-1 cleavage by thrombin results in anti
      inflammatory and barrier protective signaling provided occupation of EPCR by the
      PC gla-domain, raising the possibility that the beneficial effects of rh-APC
      might be recapitulated in vivo by administration of h-PC zymogen to patients with
      severe sepsis. Recent reports of h-PC infusion in animal models of sepsis support
      this hypothesis.

PMID- 22154247
TI  - Influence of inspiration level on bronchial lumen measurements with computed
      tomography.
AB  - BACKGROUND: Bronchial dimensions measured in CT images generally do not take
      inspiration level into consideration. However, some studies showed that the
      bronchial membrane is distensible with airway inflation. Therefore, re
      examination of the elasticity of bronchi is needed. PURPOSE: To assess the
      influence of respiration on bronchial lumen area (defined as distensibility) in
      different segmental bronchi and to explore the correlations between
      distensibility and both lung function and emphysema severity. MATERIAL AND
      METHODS: In 44 subjects with COPD related to alpha-1-antitrypsin deficiency
      (AATD), bronchial lumen area was measured in CT images, acquired at different
      inspiration levels. Measurements were done at matched locations in one apical and
      two basal segmental airways (RB1, RB10 and LB10). Airway distensibility was
      calculated as lumen area difference divided by lung volume difference. RESULTS:
      Bronchial lumen area in the lower lobes (RB10 and LB10) correlated positively
      with FEV(1)%predicted (p=0.027 for RB10; and p=0.037 for LB10, respectively).
      Lumen area is influenced by respiration (p=0.006, p=0.045, and, p=0.005 for RB1,
      RB10 and LB10, respectively). Airway distensibility was different between upper
      and lower bronchi (p<0.001), but it was not correlated with lung function.
      CONCLUSION: Lumen area of third generation bronchi is dependent on inspiration
      level and this distensibility is different between bronchi in the upper and lower
      lobes. Therefore, changes in lumen area over time should be studied whilst
      accounting for the lung volume changes, in order to estimate the progression of
      bronchial disease while excluding the effects of hyperinflation.

PMID- 22154248
TI  - On-line delay estimation for stable, unstable and integrating systems under step
      response.
AB  - A simple but effective on-line method to estimate the delay from step response,
      which can be used for stable, unstable and integrating systems, is proposed in
      this paper. The estimation and control are made simultaneously since the nominal
      delay is updated in closed-loop based on certain calculus on the output signal.
      Moreover, the approach is based on a Modified Smith Predictor and the delay
      estimation is implemented using a multi-model scheme with fixed models.
      Additionally, the convergence properties of the estimation algorithm and the
      stability analysis of the closed-loop are well-defined. Simulation examples show
      the effectiveness of the proposed method, where the delay estimation leads to an
      optimal and robust controller, tackling the uncertainty in the delay.

PMID- 22154250
TI  - Using seasonal-trend decomposition based on loess (STL) to explore temporal
      patterns of pneumonic lesions in finishing pigs slaughtered in England, 2005
      2011.
AB  - Enzootic pneumonia (EP) is responsible for considerable economic losses in pig
      production. This study analyses temporal variations of pneumonic lesions present
      in slaughtered finishing pigs utilising a novel analytical tool - STL
      decomposition. Using data collected over a 6-year period starting in July 2005,
      time-series analyses were conducted to identify trend and the presence of
      seasonal variations to support industry led measures to monitor and control this
      important respiratory disease. In England, the BPEX Pig Health Scheme monitors
      the occurrence of EP in slaughtered finished pigs by identifying its gross
      pathology, enzootic pneumonia-like (EP-like) lesions. For visual analytics, the
      monthly prevalence for EP-like lesions was modelled using STL, a seasonal-trend
      decomposition method based on locally-weighted regression. A binomial generalised
      linear mixed-effects model (GLMM), accounting for clustering at batch level, was
      used to test the significance of the trend and seasonality. A mean of 12,370 pigs
      was assessed per month across 12 pig abattoirs over the study period. A trend
      toward reduction in prevalence of EP-like lesions during the first 3 years of
      BPHS, followed by an increasing trend, was identified with STL. This feature was
      consistent with the presence of a statistically significant positive quadratic
      term ("U" shape) as identified using the GLMM inference model. November and
      December appeared in the STL explorations as higher seasonal peaks of the
      occurrence of EP-like lesions. These 2 months had a significantly higher risk of
      this disease (OR=1.38, 95% CI: 1.24-1.54 and OR=1.4, 95% CI: 1.25-1.58,
      respectively, with July taken as baseline). The results were reported back to the
      pig industry as part of the national monitoring investigations.

PMID- 22154249
TI  - Efficient surveillance of pig populations using oral fluids.
AB  - Currently virus surveillance in swine herds is constrained by the cost
      effectiveness and efficiency of sampling methods. The objective of this study was
      to assess the value of using oral fluids collected by barn personnel as a method
      of surveillance based on PCR testing. Approximately 12,150 pigs in 10 wean-to
      finish barns on 10 farms were monitored for the presence of porcine circovirus
      type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV),
      influenza A virus (IAV), and Torque teno virus genogroups 1 (TTV1) and 2 (TTV2)
      by sampling oral fluid specimens. Oral fluid samples were collected from 6 pens
      at each site starting at the time of pig placement (~3 weeks of age) and
      continuing thereafter at 2-week intervals for a period of 18 weeks. Data were
      analyzed both on a pen basis and barn basis. Overall, 508 (85%) samples were
      positive for PCV2, 73 (12%) for PRRSV, 46 (8%) for IAV, 483 (81%) for TTV2, and
      155 (26%) for TTV1 during the study period. The estimated arithmetic means of the
      quantitative PCR-positive oral fluids for PCV2, PRRSV, and IAV were 1*10(4.62),
      1*10(4.97), and 1*10(5.49)per ml. With a single exception, all barns were
      positive for PCV2 and TTV2 at every sampling point in the study. Virus detection
      varied among barns, particularly for IAV and PRRSV. The pen level, cumulative
      distribution of agent combinations between all 10 barns were statistically
      different. The most commonly observed patterns were PCV2+TTV2 (239 pen samples,
      40%), PCV2+TTV1+TTV2 (88 pen samples, 15%), and PCV2 alone (66 pen samples, 11%).
      This "proof-of-concept" project showed that a variety of viruses could be
      detected either intermittently or continuously in pig populations and
      demonstrated that barn herd virus status is highly variable, even among barns in
      the same production system. Oral fluid sampling is a promising approach for
      increasing the efficiency and cost effectiveness of virus surveillance in swine
      herds.

PMID- 22154251
TI  - [Orthostatic tremor inducing instability].
AB  - Orthostatic tremor (OT) is a neurological disease of unknown aetiology. It is
      defined by the presence of a 10-20 Hz tremor in the legs while standing still.
      Symptoms described are dizziness and instability that diminish if the patient
      sits down or leans on something; drinking small amounts of alcohol significantly
      reduces OT. Due to the dizziness and/or unsteadiness, these patients are usually
      referred to the neuro-otology department. We report 4 cases diagnosed with OT.
      The diagnosis of OT should be considered for patients with instability. The
      clinical history is a key factor to suspect this entity, and the diagnosis is
      given by the register of 10-20 Hz contractions on limb electromyography.
      Treatment for this disease consists of medical treatment; the first option is
      clonazepam.

PMID- 22154252
TI  - Effects of long duration, low dose bronopol exposure on the control of
      Ichthyophthirius multifiliis (Ciliophora), parasitising rainbow trout
      (Oncorhynchus mykiss Walbaum).
AB  - Ichthyophthirius multifiliis Fouquet, 1876 infections on intensively reared fish
      stocks can increase rapidly, which if left unmanaged, can result in the heavy
      loss of stock. The present study explores the efficacy of long duration, low dose
      (1, 2 and 5 mg L(-1)) treatments of bronopol (marketed as PycezeTM, Novartis
      Ltd.) in reducing the number of trophonts establishing on juvenile Oncorhynchus
      mykiss held under small scale culture conditions. The effect of bronopol on the
      colonisation success of infective theronts was also investigated by adding 2 mg
      L(-1) bronopol to the water prior and during the infection process. The number of
      parasites surviving on fish treated this way was compared to groups of fish that
      only received treatment after infection had occurred. The effect of bronopol on
      exiting trophonts throughout their external development to the point of theront
      release was also assessed through the delivery of 1 mg L(-1), 2 mg L(-1) and 5 mg
      L(-1) bronopol for up to 27 days consecutively (days 9-36 post-infection). The
      trial showed that a nominal dose of 2 mg L(-1) bronopol administered prior to
      infection significantly reduced the number of theronts surviving in the water
      column at the time of the initial challenge by 35-40% (P<0.05). Similarly, doses
      of 2 and 5 mg L(-1) bronopol administered as the first wave of mature I.
      multifiliis trophonts exited fish (i.e. day 11 onwards) to develop externally,
      reduced the number of trophonts establishing on fish as the second cycle of
      infection by 52-83%. Continuous application of 2 and 5 mg L(-1) bronopol
      throughout the second and third cycles of I. multifiliis infection gave further
      reductions of between 90 and 98%. The number of trophonts on the fish in the
      control tanks and those treated with 1 mg L(-1) and the 2 mg L(-1) dose at the
      time of initial infection, by comparison, were observed to increase with
      successive cycles of infection. From these small scale tank trials, this study
      demonstrates that the strategic, long duration, low dose delivery of drugs like
      bronopol can significantly reduce the number of trophonts establishing on fish
      suggesting the potential of this drug at managing I. multifiliis infections.

PMID- 22154253
TI  - Property of large conductance Ca(2+)-activated K+ channels from Fasciola hepatica
      incorporated into planar lipid bilayer.
AB  - Fasciola hepatica causes biliary epithelial hyperplasia and obstructive jaundice
      in humans and animals. Using a planar lipid bilayer technique, we further
      characterized the single channel property of large conductance K(+)-permeable
      channels that were previously identified from F. hepatica. The single channel
      conductance was 254.7+/-17.9 pS under a symmetrical 200/200 mM (cis/trans) KCl
      gradient. Open state probability (P(o)) varied from channel to channel at a given
      membrane potential and Ca(2+) concentration, but increased with voltage (-60 to
      +40 mV) and cis Ca(2+) (1-200 MUM). Under a near bi-ionic condition of 200 mM
      [K(+)](cis)/200 mM [Na(+)](trans), the permeability ratio of K(+) to Na(+) was
      5.0. Charybdotoxin (1 MUM) inhibited P(o), whereas tetraethylammonium reduced the
      conductance (K(D)=67.8mM). Taken together, the results show that the single
      channel properties of the large conductance K(+)-permeable channels in F.
      hepatica are similar to those of large conductance Ca(2+)-activated K(+) (BK)
      channels in general, but distinct from typical BK channels in the extent of
      voltage- and Ca(2+)-dependence, as well as permeability to Na(+). This study
      further reveals a variant BK channel in F. hepatica that could serve as a new
      drug target to treat fascioliasis.

PMID- 22154254
TI  - Molecular characterization of Hepatozoon spp. infection in endangered Indian wild
      felids and canids.
AB  - Hepatozoon species are parasites that infect a wide variety of domestic and wild
      animals. The objective of this study was to perform the molecular detection and
      characterization of Hepatozoon spp. in Asiatic lion, Indian tiger, Indian
      leopard, Indian wild dog, Indian domestic dog and cat based on partial 18S rRNA
      gene sequences from Hepatozoon spp. in the naturally infected animals. Hepatozoon
      spp. could be detected in blood samples of 5 out of 9 Asiatic lions, 2 out of 5
      Indian tigers, 2 out of 4 Indian leopards and 2 out of 2 Indian wild dogs and, 2
      out of 4 domestic cats and 2 out of 3 domestic dog samples by PCR. Sequencing of
      PCR amplicon and BLAST analysis of partial 18S rRNA gene sequences indicated that
      the Hepatozoon spp. in Asiatic lion, Bengal tiger, Indian leopard and domestic
      cat was Hepatozoon felis (98-99% similarity) and in the Indian wild and domestic
      dog the phylogenetic neighbour was Hepatozoon canis (97-100% similarity).
      Presence of H. felis and H. canis in both domestic and wild animals suggested
      that they are not host specific and the same parasite causes infection in
      domestic and wild felids and canids in India and from different parts of the
      world. To our knowledge, this is the first report on detection and molecular
      characterization of H. felis infection in Asiatic lions, Indian tigers, Indian
      leopards and H. canis in Indian wild dog. Hepatozoon spp. may be a potential
      pathogen and an opportunistic parasite in immuno-compromised animals and could
      thus represent a threat to endangered Indian wild felids and canids.

PMID- 22154255
TI  - Occurrence of Theileria and Babesia species in water buffalo (Bubalus babalis,
      Linnaeus, 1758) in the Hubei province, South China.
AB  - The presence and prevalence of tick-borne haemoparasites in water buffalo from
      the Hubei province, south China was investigated using the reverse line blot
      (RLB) hybridization assay and phylogenetic analysis of the parasite 18S rRNA
      gene. Theileria buffeli (19.1%) was the most frequently found species in all of
      the locations, followed by Babesia orientalis (8.9%), Babesia bovis (1.0%) and
      Babesia bigemina (0.7%). Only 12 (3.9%) of the samples had mixed infections.
      Eleven samples with single infections were selected for further characterization
      using 18S rRNA gene sequence analysis. Phylogenetic analysis showed that the
      eight T. buffeli 18S rRNA gene sequences obtained grouped into four clusters, of
      which three grouped with the known T. buffeli types B and D. The remaining five
      grouped separately from the previously describe T. buffeli types, constituting
      new T. buffeli types. The two B. bigemina 18S rRNA gene sequences obtained
      grouped closely with B. bigemina Kunming; this serves as the first report of B.
      bigemina in the Hubei province. The B. orientalis Daye 18S rRNA gene sequence
      obtained grouped closely with the previously reported B. orientalis Wuhan strain
      and with Babesia sp. Kashi 1 and Kashi 2.

PMID- 22154256
TI  - Manipulating small ruminant parasite epidemiology through the combination of
      nutritional strategies.
AB  - It is increasingly being recognized that non-chemical parasite control strategies
      may need to be combined to control more effectively gastrointestinal parasitism,
      result in resilient production systems and reduce reliance on anthelmintics.
      Here, we consider if and how metabolizable protein (MP) supplementation and anti
      parasitic plant secondary metabolites (PSM) may modulate parasite epidemiology
      through intervention in pasture contamination, development of infection on
      pasture and larval challenge as target processes. We then propose that combining
      two or more non-chemical parasite control strategies may have additive effects on
      host resistance, especially if the individual strategies target different drivers
      of parasite epidemiology, different processes in the parasite life cycle or
      different phases of acquired immunity to parasites. This epidemiological
      framework is used to review recent findings on combining maternal MP
      supplementation and grazing the PSM-rich bioactive forage chicory as an example
      of combining nutritional treatments to manipulate parasite epidemiology in a
      temperate production system. In the absence of available data for combined
      nutritional strategies in tropical production systems, we make predictions on the
      consequences of combining such strategies in these systems. We conclude that
      currently published studies on combining nutritional strategies under temperate
      conditions show potential to improve additively host resilience and reduce
      reliance on anthelmintics; however, effects on epidemiology have to date not
      shown the additive results hypothesized. The framework developed may assist
      further in evaluating combined (nutritional) strategies to manipulate parasite
      epidemiology.

PMID- 22154257
TI  - Novel approaches for the control of helminth parasites of livestock VI: summary
      of discussions and conclusions.
AB  - Gastrointestinal helminth parasites impact on livestock production systems
      throughout the world, and the use of anthelmintics to control this problem has
      lead to the inevitable development of populations of helminths resistant to these
      treatments. This, coupled with consumer desires for minimal chemical inputs into
      food and fibre production, has prompted research into non-chemical approaches to
      helminth control. Scientists of the "Novel Approaches to the Control of Helminth
      Parasites of Livestock" group met for the 6th time in August 2010 and this paper
      summarises that meeting. Six scientific sessions addressed current approaches and
      topics of interest through formal presentations and discussion of issues raised
      by the contributing authors. Close interaction between researchers and extension
      specialists during the meeting has contributed to enhanced prospects for field
      application of research outcomes in the future.

PMID- 22154258
TI  - Integrated parasite management: products for adoption by the Australian sheep
      industry.
AB  - The increasing cost of production loss caused by gastrointestinal nematodes (GIN)
      highlights the importance of good control programs. However, the endemic nature
      of anthelmintic resistance also reminds of the need for nonchemical options. Both
      chemical and nonchemical control options need to be integrated into regional
      parasite management programs (IPM) with the emphasis on component options
      determined by factors such as major GIN species, regional climate, property size
      and enterprise structure. The Integrated Parasite Management of Sheep project was
      established to develop and demonstrate regional parasite control programs, that
      integrated chemical and nonchemical options, for the main sheep-producing regions
      of Australia. The project included research about the ecology of the main endo
      and ecto-parasites of sheep and a national survey of parasite control practices
      by sheep producers. IPM approaches developed for two contrasting regions of
      Australia are discussed. Barriers for the adoption of IPM programs include
      perceived complexity associated with a multi-component approach, time
      requirements and difficulty. Facilitating the industry adoption of IPM programs
      is discussed with relevance to the use of small group extension and involvement
      of the commercial sector. Perceptions of complexity of IPM may be managed by
      facilitating adoption of components in a step-wise process such that learning
      outcomes accumulate over time. Extension efforts must address the needs of
      industry sectors other than sheep producers and explore user pay approaches. The
      success of these approaches will depend on the relation of the extra profit to
      producers, through adoption of IPM programs, with remuneration sufficient to
      attract a commercial service.

PMID- 22154259
TI  - Optimized photoluminescence of SrB2O4:Eu3+ red-emitting phosphor by charge
      compensation.
AB  - A novel red-emitting phosphor, SrB(2)O(4):Eu(3+), was synthesized by high
      temperature solid-state reaction and its photoluminescence properties were
      studied. The emission spectrum consists of four major emission bands. The
      emission peaks are located at 593, 612, 650 and 703nm, corresponding to the
      (5)D(0)->(7)F(1), (5)D(0)->(7)F(2), (5)D(0)->(7)F(3) and (5)D(0)->(7)F(4) typical
      transitions of Eu(3+), respectively. The effects of Eu(3+) doping content and
      charge compensators (Li(+), Na(+), K(+)) on photoluminescence of
      SrB(2)O(4):Eu(3+) phosphor were studied. The results show that the emission
      intensity can be affected by above factors and Na(+) is the optimal charge
      compensator for SrB(2)O(4):Eu(3+). The photoluminescence of NaSrB(2)O(4):Eu(3+)
      was compared with that of Y(2)O(2)S:Eu(3+). It implies that SrB(2)O(4):Eu(3+) is
      a good candidate as a red-emitting phosphor pumped by near-ultraviolet (NUV)
      InGaN chip for fabricating white light-emitting diodes (WLEDs).

PMID- 22154260
TI  - Quantum-chemical, spectroscopic and X-ray diffraction studies of (E)-2-[(2
      Bromophenyl)iminomethyl]-4-trifluoromethoxyphenol.
AB  - The Schiff base compound (E)-2-[(2-Bromophenyl)iminomethyl]-4
      trifluoromethoxyphenol has been synthesised and characterised by IR, UV-vis, and
      X-ray single-crystal determination. The molecular geometry from X-ray
      determination of the title compound in the ground state has been compared using
      the Hartree-Fock (HF) and density functional theory (DFT) with the 6-311++G(d,p)
      basis set. The calculated results show that the DFT and HF can well reproduce the
      structure of the title compound. Using the TD-DFT and TD-HF methods, electronic
      absorption spectra of the title compound have been predicted and good agreement
      with the TD-DFT method and the experimental determination was found. The
      predicted nonlinear optical properties of the title compound are much greater
      than those 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- 22154261
TI  - A study of the molecular structure and vibrational spectra of 1,3-dichloro-2
      propanol and 1,1,1-trichloro-2-methyl-2-propanol (chlorobutanol).
AB  - The conformational stability of 1,3-dichloro-2-propanol and 1,1,1-trichloro-2
      methyl-2-propanol (chlorobutanol) was investigated by the DFT-B3LYP/6-311+G**,
      MP2/6-311+G** and MP4(SDQ)/6-311+G** levels of theory. From the calculations
      chlorobutanol was predicted to exist in a non-planar gauche structure. The planar
      cis and trans structures of chlorobutanol were calculated to be about 3kcal/mol
      higher in energy than the gauche structure. From the calculations 1,3-dichloro-2
      propanol was predicted to exist in a Ggg1 and Ggg conformational mixture at
      ambient temperature. In the low energy structures of both alcohols the non-bonded
      Cl?H(O) distance was calculated to be of about 2.6-2.7A. The observation of a
      broad and very intense band at about 3400cm(-1) in the infrared spectra of the
      two alcohols supports the presence of strong intermolecular Cl?H(O) dipolar
      interactions in their condensed phases. The analysis of the Raman spectra of 1,3
      dichloro-2-propanol suggests the presence of a second high energy Ggg structure
      of the dichloride at room temperature. The vibrational frequencies of 1,3
      dichloro-2-propanol and chlorobutanol in their low energy structures were
      computed at the B3LYP level and tentative vibrational assignments were made for
      their normal modes on the basis of combined calculated and experimental data.

PMID- 22154262
TI  - Electronic absorption spectrum of monoamine tetraphenylporphyrin with the
      complexon of ethylenediaminetetraacetic acid as substitute.
AB  - In the framework of density functional theory the equilibrium geometry of the
      ground electronic state of monoamine tetraphenylporphyrin with the complexon of
      ethylenediaminetetraacetic acid was found using B3LYP functional and 6-31G(d,p)
      basis set. Electronic absorption spectrum of this molecule in ethanol solution
      was measured in the range of 300-600nm and interpreted using the PCM/TDDFT method
      (with the B3LYP, CAMB3LYP, M06-2X functionals) with 6-31G(d,p) and 6-31++G(d,p)
      basis sets. The observed and calculated line positions and intensities are well
      agreed.

PMID- 22154263
TI  - UV-excited red-emitting phosphor Eu3+-activated Ca9Y(PO4)7.
AB  - Red-emitting phosphor Ca(9)Y(PO(4))(7):Eu(3+) were fabricated by solid-state
      reactions at high temperature. X-ray diffraction analysis revealed that
      Ca(9)Y(PO(4))(7) doped with 3mol% of Eu(3+) (Ca(9)Y(0.97)(PO(4))(7):0.03Eu(3+))
      was pure orthorhombic phase. The photoluminescence study shows that the intensity
      of electric dipole transition ((5)D(0)->(7)F(2)) at 613nm dominates over that of
      magnetic dipole transition ((5)D(0)->(7)F(1)) at 594nm. The optimum concentration
      of Eu(3+) for the highest luminescence is found to be 3mol%. The PL excitation
      spectrum is composed of CT of Eu-O and excitation lines of Eu(3+) ions. The
      strongest excitation lines appeared at 392nm. The integral intensity of the
      emission spectrum of Ca(9)Y(0.97)(PO(4))(7):0.03Eu(3+) excited at 392nm is about
      twice as strong as that of Y(2)O(3):0.05Eu(3+) commercial red phosphor. The color
      coordinates, quantum yield and lifetime for Ca(9)Y(0.97)(PO(4))(7):0.03Eu(3+)
      were measured. All the spectrum features indicate that Ca(9)Y(PO(4))(7):Eu(3+)
      might be a promising phosphor for display devices or w-LEDs.

PMID- 22154264
TI  - Specific features of Tm3+ doped BiB3O6 glasses fluorescence spectra and their
      kinetics.
AB  - Synthesis and spectral fluorescent features of the thulium-doped BiB(3)O(6)
      glasses are presented. All spectra were recorded using a pulsed (pulse energy ca.
      1MUJ, pulse duration 10ns) 355nm third harmonic of 10kHz Nd:YAG laser as an
      excitation source. A laser beam was focused in a backscattering geometry onto
      about 1mm(2) spot on the surface of a sample. The Andor SR-303i spectrograph
      equipped with an Andor DH-501 intensified charge coupled device with spectral
      resolution up to 1nm was used as a spectra recorder. The time-resolution of this
      system can be as low as 5ns. The decay kinetics was derived from integrated time
      resolved spectra. Additionally the absorption and excitation spectra were
      measured. The main parameters of the Judd-Ofelt analysis were calculated and
      comparison of the obtained results with corresponding data for other materials
      was carried out.

PMID- 22154265
TI  - On the spectroscopic analyses of (E)-3-(dicyclopropyl methylene)-dihydro-4-[1
      (2,5 dimethylfuran-3-yl) ethylidene]furan-2,5-dione.
AB  - In this work, a combined experimental and theoretical study on molecular
      structure and vibrational frequencies of (E)-3-(dicyclopropyl methylene)-dihydro
      4-[1-(2,5 dimethylfuran-3-yl) ethylidene] furan-2,5-dione [DCPF] were reported.
      The FT-IR spectra of DCPF isomers are recorded in the solid phase. The
      equilibrium geometries, harmonic vibrational frequencies, thermo-chemical
      parameters, total dipole moment and HOMO-LUMO energies are calculated by density
      functional theory DFT/B3LYP utilizing 6-311G(d,p) basis set. Results showed that
      scaled frequencies are in good agreement with experimental values. The HOMOs and
      the LUMOs energies of DCPF isomers were 3.8 and 2.7eV for E and C
      isomers,respectively.

PMID- 22154266
TI  - The interaction between lanthanide (III) and N-terminal domain of Euplotes
      octocarinatus centrin.
AB  - Centrin, a member of calcium-binding proteins, is an essential component for
      microtubule-organizing center (MTOC). Lanthanide (Ln) ions can increase amounts,
      enhance stability and orderliness of microtubules which is an important component
      of cytoskeleton. To investigate the structural basis of the effect of Ln ions on
      orderliness of microtubules, we focused on the interactions between the isolated
      N-terminal domain of Euplotes centrin (N-EoCen) and Ln by some combined
      biophysical and biochemical methods. Our results suggest that Ln ions may bind to
      the canonical calcium binding sites on N-EoCen. Taking advantage of ligand
      competition, we first determined the metal-binding affinities of Nd(3+), Eu(3+),
      Gd(3+) and Tm(3+) with N-EoCen. Major changes of N-EoCen in secondary and
      tertiary structure are noted while Ln ions bind with N-EoCen through CD spectra
      and 2-p-toluidinylnaphthalene-6-sulfonate (TNS) fluorescence. N-EoCen exists in
      the form of monomer and dimer in the presence of Ln ions. These results can
      provide some insights into the structural basis of how Ln ions achieve biological
      effect in cell through the centrin protein.

PMID- 22154267
TI  - Spectrometry researches on interaction and sonodynamic damage of riboflavin (RF)
      to bovine serum albumin (BSA).
AB  - In this paper, the riboflavin (RF) was used to study the interaction and
      sonodynamic damage to bovine serum albumin (BSA) by fluorescence and UV-vis
      spectroscopy. The results showed that the RF could efficiently bind to BSA in
      aqueous solution. Under ultrasonic irradiation, the RF could obviously damage the
      BSA. In addition, synchronous fluorescence spectroscopy revealed that the RF
      showed more accessible to tryptophan (Trp) residues than to tyrosine (Tyr)
      residues. Also, it damaged Trp residues more seriously than Tyr residues under
      ultrasonic irradiation. At last, the generation of reactive oxygen species (ROS)
      in sonodynamic process was estimated by the method of Oxidation-Extraction
      Spectrometry (OES). And then, several radical scavengers were used to determine
      the kind of ROS. It was found that at least the singlet oxygen ((1)O(2)) and
      hydroxyl radicals (*OH) were generated.

PMID- 22154268
TI  - Molecular structural, IR and NMR spectroscopic studies on the four isomers of
      thiotriazinone by DFT and HF calculations.
AB  - One of the isomers of thiotriazinone, 6-hydroxy-2-methyl-3-thioxo-2H-1,2,4
      triazin-5-one, was characterized by single-crystal X-ray diffraction. The
      compound crystallizes in the monoclinic space group P2(1)/c with a=9.5837(19)A,
      b=5.7006(11)A, c=15.065(4)A, alpha=90 degrees , beta=128.540(19) degrees  and
      gamma=90 degrees . The molecular geometries and vibrational frequencies of the
      four isomers of thiotriazinone in the ground state have been calculated using the
      density functional theory (DFT) and Hartree-Fock (HF) methods with 6-311++G(d,p)
      basis set, and compared with the experimental data. Gauge-including atomic
      orbital (GIAO) (13)C and (1)H NMR chemical shift values were calculated by DFT/6
      311++G(2d,2p) and HF/6-311++G(2d,2p) methods, and compared with the experimental
      data. The calculated results show that the optimized geometries can well
      reproduce the crystal structural parameters. The theoretical IR spectra and (13)C
      and (1)H NMR chemical shift values also show good agreement with experimental
      data. In addition, frontier molecular orbitals (FMO) and molecular electrostatic
      potential (MEP) analysis of the four isomers were investigated using theoretical
      calculations.

PMID- 22154269
TI  - Surface Enhanced Raman Spectroscopy (SERS) and multivariate analysis as a
      screening tool for detecting Sudan I dye in culinary spices.
AB  - Raman spectroscopy combined with multivariate analysis was evaluated as a tool
      for detecting Sudan I dye in culinary spices. Three Raman modalities were
      studied: normal Raman, FT-Raman and SERS. The results show that SERS is the most
      appropriate modality capable of providing a proper Raman signal when a complex
      matrix is analyzed. To get rid of the spectral noise and background, Savitzky
      Golay smoothing with polynomial baseline correction and wavelet transform were
      applied. Finally, to check whether unadulterated samples can be differentiated
      from samples adulterated with Sudan I dye, an exploratory analysis such as
      principal component analysis (PCA) was applied to raw data and data processed
      with the two mentioned strategies. The results obtained by PCA show that Raman
      spectra need to be properly treated if useful information is to be obtained and
      both spectra treatments are appropriate for processing the Raman signal. The
      proposed methodology shows that SERS combined with appropriate spectra treatment
      can be used as a practical screening tool to distinguish samples suspicious to be
      adulterated with Sudan I dye.

PMID- 22154270
TI  - From genes to phenotypes - evaluation of two methods for the SNP analysis in
      archaeological remains: pyrosequencing and competitive allele specific PCR
      (KASPar).
AB  - The amplification length of the DNA fragments is one major limitation of most
      paleogenetic analyses. Routinely, only fragments below 200 bp can be amplified,
      significantly reducing the content of genetic information. Although overlapping
      PCR strategies and next generation sequencing techniques have strongly improved
      data mining recently, these methods are still expensive and time consuming. In
      contrast, SNP analyses are easy to handle, fast and cheap. In this study, we
      compare two methods of SNP detection as to efficiency, cost and reliability for
      their use in ancient DNA applications: pyrosequencing and competitive allele
      specific PCR (KASPar). Our sample set consisted of 16 horse bones from two
      Scythian graves (600-800 BC). In conclusion, both approaches produced reliable
      results for most allelic patterns. But an indel of 11 bp (ASIP) could not be
      detected in the KASPar approach and produced problems in the pyrosequencing
      method (70% success rate). In such cases, we recommend checking allelic
      distribution using a gel approach or capillary sequencing. Overall, in comparison
      with the traditional mode of ancient DNA investigations (PCR, cloning, capillary
      sequencing), both approaches are superior for SNP analyses especially of large
      sample sets.

PMID- 22154271
TI  - Prospective changes in body image dissatisfaction among adolescent bariatric
      patients: the importance of body size estimation.
AB  - BACKGROUND: Body image dissatisfaction (BID) is pervasive among patients
      presenting for bariatric surgery but improves significantly postoperatively.
      These findings have been determined primarily from studies of adults. The
      objective of the present study was to examine the changes in BID among
      adolescents with extreme obesity from baseline/preoperatively to 6 and 12 months
      after receiving bariatric surgery at a pediatric medical center using body size
      estimation. METHODS: BID was prospectively assessed among 16 adolescent bariatric
      patients (mean age 16.3 +/- 1.2 years, mean body mass index [BMI] 66.2 +/- 12.0,
      67% female) using a standard visual/perceptual measure (i.e., Stunkard Figure
      Rating Scale). Participants identified their current and ideal body size, with a
      discrepancy score (current minus ideal) indicating BID. The body size estimation
      ratings were compared with attitudinal (i.e., Impact of Weight on Quality Of Life
      Kids: Body Esteem and Self-Perception Profile for Adolescents: Physical
      Appearance) body image scores, BMI, and total weight-related quality of life.
      RESULTS: A significant reduction occurred in the current body size (from 7.9 to
      6.4, P <.001) from baseline to 6 months but not from 6 to 12 months. The current
      body size was related to BMI and percentage of excess weight loss but not
      attitudinal body image at each follow-up point. A smaller discrepancy (current
      minus ideal) was associated with greater total weight-related quality of life (r
      = -.68), with a trend toward significance for body esteem (r = -.65) at 12
      months. CONCLUSION: Adolescents undergoing bariatric surgery experience a
      significantly decreased BID within the first 12 months after surgery, with the
      most substantial change occurring from baseline to 6 months. The postoperative
      weight-related quality of life is more closely associated with the body size
      discrepancy than with the current body size.

PMID- 22154272
TI  - Increased levels of chemerin and its receptor, chemokine-like receptor-1, in
      obesity are related to inflammation: tumor necrosis factor-alpha stimulates mRNA
      levels of chemerin in visceral adipocytes from obese patients.
AB  - BACKGROUND: Chemerin is a novel adipokine that regulates adipocyte development
      and metabolic function and glucose metabolism. Our aim was to determine the
      effect of chemerin and its receptor, chemokine-like receptor-1, in obesity
      associated low-grade chronic inflammation, exploring its circulating and gene
      expression levels in obesity and the effect of weight loss and to analyze the
      effect of the stimulation with tumor necrosis factor-alpha in human visceral
      adipocytes at a University hospital. METHODS: We included 52 women (16 lean and
      36 obese) in the present study. The plasma concentrations of chemerin and the
      expression levels of chemerin and its receptor in visceral adipose tissue were
      analyzed. The chemerin concentrations were also measured before and after weight
      loss achieved by Roux-en-Y gastric bypass (n = 26). RESULTS: The circulating
      concentrations and visceral adipose tissue expression of chemerin were increased
      in obese patients (P < .01) and were associated with well-established markers of
      inflammation (P < .001). Gene expression levels of chemokine-like receptor-1
      followed the same trend and were upregulated (P < .05) in human obesity. Elevated
      chemerin levels in obese patients did not change after Roux-en-Y gastric bypass
      weight loss. Tumor necrosis factor-alpha treatment significantly enhanced (P <
      .05) the mRNA levels of chemerin in human visceral adipocytes, but the gene
      expression levels of chemokine-like receptor-1 were not affected. CONCLUSION: The
      increased levels of chemerin in obesity and its positive association with
      inflammation suggest a role for this chemoattractant protein in the changes that
      take place in visceral adipose tissue in the presence of energy surplus,
      establishing a link between inflammation and the greater risk of the development
      of metabolic disease.

PMID- 22154273
TI  - River loads of suspended solids, nitrogen, phosphorus and herbicides delivered to
      the Great Barrier Reef lagoon.
AB  - Degradation of coastal ecosystems in the Great Barrier Reef (GBR) lagoon,
      Australia, has been linked with increased land-based runoff of suspended solids,
      nutrients and pesticides since European settlement. This study estimated the
      increase in river loads for all 35 GBR basins, using the best available estimates
      of pre-European and current loads derived from catchment modelling and
      monitoring. The mean-annual load to the GBR lagoon for (i) total suspended solids
      has increased by 5.5 times to 17,000ktonnes/year, (ii) total nitrogen by 5.7
      times to 80,000tonnes/year, (iii) total phosphorus by 8.9 times to
      16,000tonnes/year, and (iv) PSII herbicides is 30,000kg/year. The increases in
      river loads differ across the 10 pollutants and 35 basins examined, reflecting
      differences in surface runoff, urbanisation, deforestation, agricultural
      practices, mining and retention by reservoirs. These estimates will facilitate
      target setting for water quality and desired ecosystem states, and enable
      prioritisation of critical sources for management.

PMID- 22154274
TI  - Radionuclide monitoring in molluscs inhabiting intertidal region near a nuclear
      installation, Gulf of Mannar, India.
AB  - Protection of non-human biota from ionizing contaminants, especially in the
      vicinity of nuclear installations is a very important aspect for nuclear
      engineers and ecologists. In this view, a baseline data on the activity
      concentration of (210)Po and (210)Pb were quantified in different tissues of
      molluscs inhabiting the intertidal region along the coast of Kudankulam. The
      activity concentration was noticed higher in the organs associated with digestion
      and metabolism. Filter feeding bivalve molluscs registered the maximum activity
      of (210)Po in their whole body compared to grazing gastropods. (210)Po:(210)Pb
      ratio was calculated to be greater than unity in most of the analysed tissues.
      The ecological sensitivity of molluscs to the radiation exposure and the safeness
      of the environment was analysed by calculating the external and internal dose
      rate. The hazard quotient for molluscs was lesser than the global bench mark dose
      rate of 10 MUGyh(-1).

PMID- 22154275
TI  - Long term monitoring of photosystem II herbicides--correlation with remotely
      sensed freshwater extent to monitor changes in the quality of water entering the
      Great Barrier Reef, Australia.
AB  - Photosystem II (PSII) herbicides are used in large quantities on agricultural
      lands adjoining the Great Barrier Reef (GBR). Routine monitoring at 14 sites in
      inshore waters of the GBR using passive sampling techniques detected diuron (32
      94% of sampling periods) at maximum concentrations of 1.7-430ng L(-1) in the
      relatively pristine Cape York Region to the Mackay Whitsunday Region,
      respectively. A PSII herbicide equivalent (PSII-HEq) index developed as an
      indicator for reporting was dominated by diuron (average contribution 89%) and
      typically increased during the wet season. The maximum PSII-HEq indicates the
      potential for photosynthetic inhibition of diatoms, seagrass and coral-symbionts.
      PSII herbicides were significantly positively correlated with remotely sensed
      coloured dissolved organic matter, a proxy for freshwater extent. Combining these
      methods provides for the first time the potential to cost-effectively monitor
      improvements in water quality entering the GBR with respect to exposure to PSII
      herbicides.

PMID- 22154276
TI  - Impacts of an uncontrolled phosphogypsum dumpsite on summer distribution of
      phytoplankton, copepods and ciliates in relation to abiotic variables along the
      near-shore of the southwestern Mediterranean coast.
AB  - In connection with the Taparura Project, studies of spatial distribution of the
      crustacean zooplankton community, nutrients, phytoplankton and ciliates were
      conducted in July 2007 at 45 stations spread over fifteen transects along the
      coast north of Sfax. The results showed that the N/P ratio was lower than the
      Redfield ratio, suggesting potential N limitation. Phytoplankton was
      characterised by the proliferation of several diatoms, while ciliates were
      largely dominated by spirotrichs. Copepods were the most abundant zooplankton
      present during the entire study period, comprising 61% of the total zooplankton
      community. Twelve copepod families were identified at every station, with a high
      percentage of Oithonidae (77% of copepods) dominated by Oithona nana. The
      abundance of this species was correlated with that of diatoms,
      Cocoolithophorideae and ciliated Colpodea, suggesting that O. nana may feed on a
      wide range of prey. Despite human pressure and industrial activities, the coastal
      waters north of Sfax showed a wide diversity of phytoplankton, ciliates and
      zooplankton.

PMID- 22154277
TI  - Tibial rotation during pivoting in anterior cruciate ligament reconstructed knees
      using a single bundle technique.
AB  - BACKGROUND: Anterior cruciate ligament reconstruction does not necessarily
      restore normal knee movement. Increased tibial rotation has previously been noted
      during pivoting activities and may be due to the orientation of the anterior
      cruciate ligament graft associated with traditional single bundle reconstruction
      techniques. Recent research has shown that it is possible to limit rotation
      during level walking using a single bundle anterior cruciate ligament
      reconstruction. This study evaluated rotational knee kinematics during a pivot
      task in a group of patients who had undergone anterior cruciate ligament
      reconstruction using a single bundle technique and compared the findings to a
      normal control group. METHODS: In 27 anterior cruciate ligament reconstruction
      and 25 control participants, internal-external rotation was measured during a
      descend stairs and pivot task in a gait laboratory. FINDINGS: Results showed that
      the anterior cruciate ligament reconstruction patients had less internal tibial
      rotation (for both range of rotation and maximum rotation) than the control
      participants (effect size=0.7). INTERPRETATION: These results suggest that it is
      possible to limit rotation after anterior cruciate ligament reconstruction using
      a single bundle technique, even during a pivoting movement that places a high
      rotational load at the knee joint. The positioning of the femoral tunnel in a
      more anatomical position may be responsible for the reduced tibial rotation.

PMID- 22154278
TI  - Oncogenic pathways, molecularly targeted therapies, and highlighted clinical
      trials in non-small-cell lung cancer (NSCLC).
AB  - Non-small-cell lung cancer (NSCLC) has recently been associated with interesting
      molecular characteristics that have important implications in carcinogenesis and
      response to targeted therapies. The unsatisfactory treatment outcomes in advanced
      NSCLC with respect to long-term survival rates may be improved through a better
      understanding of the molecular etiology of this disease. For instance, several
      molecular alterations have been defined as "driver mutations," such as mutations
      in epidermal growth factor receptor (EGFR), Kirsten-rous avian sarcoma (KRAS),
      and a chromosome 2p inversion producing an EML4-ALK fusion gene (echinoderm
      microtubule-associated protein-like 4 fused with the anaplastic lymphoma kinase).
      Other key signaling pathways such as RAS/RAF/MEK, PI3K/AKT/mTOR (mammalian target
      of rapamycin), mesenchymal-epithelial transition (MET) kinase, LKB1, and insulin
      like growth factor 1 (IGF-1) receptor (IGF-1R) have also been identified as novel
      targets for lung cancer treatment. In this review we focus on the molecular
      discoveries that have led to the clinical applications and trials of novel
      targeted agents, including the clinical trials that selectively studied patients
      who were predicted to achieve the greatest benefit based on the expression of
      correlative biomarkers.

PMID- 22154279
TI  - Anticipatory postural adjustments in individuals with multiple sclerosis.
AB  - Individuals with multiple sclerosis (MS) frequently exhibit difficulties in
      balance maintenance. It is known that anticipatory postural adjustments (APAs)
      play an important role in postural control. However, no information exists on how
      people living with MS utilize APAs for control of posture. A group of individuals
      with MS and a group of healthy control subjects performed rapid arm flexion and
      extension movements while standing on a force platform. Electromyographic (EMG)
      activity of six trunk and leg muscles and displacement of center of pressure
      (COP) were recorded and quantified within the time intervals typical of APAs.
      Individuals with MS demonstrated diminished ability to produce directional
      specific patterns of anticipatory EMGs as compared to control subjects. In
      addition, individuals with MS demonstrated smaller magnitudes of anticipatory
      muscle activation. This was associated with larger displacements of the COP
      during the balance restoration phase. These results suggest the importance of
      anticipatory postural control in maintenance of vertical posture in individuals
      with MS. The outcome of the study could be used while developing rehabilitation
      strategies focused on balance restoration in individuals with MS.

PMID- 22154280
TI  - [A prospective, observational severe sepsis/septic shock registry in a tertiary
      hospital in the province of Guipuzcoa (Spain)].
AB  - OBJECTIVE: To determine the epidemiological and clinical characteristics of the
      patients with severe sepsis/septic shock admitted to the ICU of Donostia Hospital
      (Guipuzcoa, Spain), analyzing the prognostic factors and comparing them with the
      existing data at national level. DESIGN: A prospective observational study was
      carried out during a consecutive 3-year period (1 Feb. 2008-31 Dec. 2010).
      SETTING: The ICU of Donostia Hospital, the only third level hospital in the
      province of Guipuzcoa, with a recruitment population of 700,000 inhabitants.
      RESULTS: In the course of the study period, 6,263 patients were admitted to our
      Department: 2,880 were non-coronary patients, and 511 suffered a severe sepsis or
      septic shock episode upon admission or during their stay in the ICU. Males
      predominated (66.5%), the mean age was 63 years, and the mean Acute Physiology
      And Chronic Health Evaluation II (APACHE II) score was 21. Most cases were
      medical (68%) and were admitted from hospital wards (53.5%). The most frequent
      origin was pneumonia (24%). The great majority of the cases (73%) corresponded to
      septic shock. Hemodynamic alterations were the most frequent disorders, followed
      by renal and respiratory impairment. Noradrenalin was used as vasoactive drug in
      all shock patients; over one-half required mechanical ventilation (MV), and one
      third required continuous venous-venous hemodiafiltration (CVVHDF). Interventions
      frequently used in the management of these patients comprised blood cultures or
      corticosteroid use, while other measures such as activated protein C were little
      used. The mortality rate in the ICU was 20.8%, with a mean stay in the Unit of 14
      days. The parameters associated to mortality in the multivariate analysis
      included the presence of hypoglycemia, respiratory dysfunction, the need for MV,
      lactic acid elevation and thrombocytopenia in the first 24 hours, together with
      an origin of sepsis either in the ICU or in the hospital. CONCLUSIONS: Severe
      sepsis is frequent in our unit, generating important morbidity and hospital stay,
      as well as high mortality. The epidemiological and clinical characteristics of
      our patients are similar to those described globally at national level.
      Considering our data in complying with the different treatment measures, it is
      clear that there is still room for improvement.

PMID- 22154281
TI  - [Relationship between the alveolar-arterial oxygen gradient and PaO2/FiO2
      introducing PEEP into the model].
AB  - OBJECTIVES: To determine whether the alveolar-arterial oxygen gradient (Grad[A
      a]O2) helps confirm the influence of PEEP on PaFi (PaO2/FiO2). DESIGN:
      Observational study; we used linear regression to perform a multivariate study to
      improve the PaFi formula by taking PEEP into account. SETTING: Tertiary hospital.
      PATIENTS: We included all patients who were admitted to the intensive care unit,
      regardless of pulmonary damage. VARIABLES: We recorded personal history, clinical
      judgment, intensive care data, severity scores on the first day and progression.
      Two calculated variables: PaFi and Grad(A-a)O2. RESULTS: A total of 956 patients
      were included: 63.9% men; median age 68 years. On the first day, 31.8% did not
      have mechanical ventilation (MV), 13.1% had non-invasive MV and 55.1% had
      invasive MV. PaFi values: 32.9% 0-200, 32.2% 201-300, and 34.8% >300. PEEP
      values: 0-5 69.8%, 6-10 27.5% and >10 2.6%. We observed a correlation (Pearson)
      between Grad(A-a)O2 and PaFi of -0.84 (p<0.001). On performing multiple
      regression (dependent variable: Grad[A-a]O2), the following variables were
      included in the model: PaFi, PEEP, APACHE IV and SOFA; coefficient of
      determination (R2) of 0.62 without PEEP and 0.72 with PEEP. We changed the PaFi
      formula, referring to it as PaFip (PaFi plus PEEP): Ln (PaFi/[PEEP+12]).
      Correlation index between PaFip and Grad(A-a)O2: -0.9 (p<0.001). We performed
      linear regression (dependent variable: Grad[A-a]O2) and used PaFip instead of
      PaFi. Only PaFi remained in the model, and was discretely complemented by APACHE
      IV; R2=0.8. CONCLUSIONS: By adding PEEP to the PaFi model (PaFip), we clearly
      improve the latter, as reflected by a better goodness of fit.

PMID- 22154282
TI  - Rapid spectroscopic velocity quantification using periodically oscillating
      gradients.
AB  - In this work two spectroscopic methods are described which allow rapid flow
      velocity quantification in the presence of a parabolic velocity distribution.
      This method requires only a single excitation and is based on flow encoding by
      periodically oscillating gradients. In the shown spin echo variant additional
      refocusing pulses correct for field inhomogeneities. A theoretical model is
      introduced, which describes the course of the derived spectra even in high flow
      region, where a significant part of the encoded spins leaves the sensitive area
      of the coil during data acquisition (outflow-effect). It was demonstrated that
      both methods can quantify flow velocities within the velocity range of 1mm/s up
      to 36 cm/s in the presence of a parabolic flow velocity distribution. The maximum
      velocity of the parabolic distribution is indicated in this method by a peak in
      the acquired spectrum from which the velocity could be quantified. Flow velocity
      quantification by periodically oscillating gradients seems a reasonable and fast
      alternative to established imaging techniques.

PMID- 22154283
TI  - Multisite EPR oximetry from multiple quadrature harmonics.
AB  - Multisite continuous wave (CW) electron paramagnetic resonance (EPR) oximetry
      using multiple quadrature field modulation harmonics is presented. First, a
      recently developed digital receiver is used to extract multiple harmonics of
      field modulated projection data. Second, a forward model is presented that
      relates the projection data to unknown parameters, including linewidth at each
      site. Third, a maximum likelihood estimator of unknown parameters is reported
      using an iterative algorithm capable of jointly processing multiple quadrature
      harmonics. The data modeling and processing are applicable for parametric
      lineshapes under nonsaturating conditions. Joint processing of multiple harmonics
      leads to 2-3-fold acceleration of EPR data acquisition. For demonstration in two
      spatial dimensions, both simulations and phantom studies on an L-band system are
      reported.

PMID- 22154284
TI  - Selecting analytical target pesticides in monitoring: Sensitivity analysis and
      scoring.
AB  - Measuring river water concentrations of all pesticides applied in a catchment
      area is a daunting task. This study aims to develop new score tables for
      selecting analytical target pesticides. Sensitivity analyses were conducted using
      a diffuse pollution hydrologic model to quantitatively evaluate the influence of
      pesticide properties (e.g., log K(OC), degradability [half-life]) on
      concentrations of rice-farming pesticides in river water. Using the results of
      the analyses, score tables were systematically designed for the pesticide
      properties such that the sum of the scores for a particular pesticide, designated
      as the contamination index, was proportional to the expected/predicted
      concentration of that pesticide in river water. The contamination indexes for
      pesticides applied in three river basins were calculated and compared with the
      corresponding observed pesticide concentrations. Correlations between
      contamination indexes and observed concentrations were fairly good. Pesticides
      were ranked according to the quotients obtained by dividing the pesticide
      concentrations predicted from the contamination indexes by the corresponding
      drinking-water quality guideline values, and pesticide candidates to be monitored
      were successfully selected on the basis of a threshold quotient.

PMID- 22154285
TI  - Characterization of humic acid reactivity modifications due to adsorption onto
      alpha-Al2O3.
AB  - Adsorption of purified Aldrich humic acid (PAHA) onto alpha-Al(2)O(3) is studied
      by batch experiments at different pH, ionic strength and coverage ratios R (mg of
      PAHA by m(2) of mineral surface). After equilibration, samples are centrifuged
      and the concentration of PAHA in the supernatants is measured. The amount of
      adsorbed PAHA per m(2) of mineral surface is decreasing with increasing pH. At
      constant pH value, the amount of adsorbed PAHA increases with initial PAHA
      concentration until a pH-dependent constant value is reached. UV/Visible specific
      parameters such as specific absorbance SUVA(254), ratio of absorbance values
      E(2)/E(3) and width of the electron-transfer absorbance band Delta(ET) are
      calculated for supernatant PAHA fractions of adsorption experiments at pH 6.8, to
      have an insight on the evolution of PAHA characteristics with varying coverage
      ratio. No modification is observed compared to original compound for R >= 20
      mg(PAHA)/g(alpha)(-)(A)12(O)3. Below this ratio, aromaticity decreases with
      initial PAHA concentration. Size-exclusion chromatography - organic carbon
      detection measurements on these supernatants also show a preferential adsorption
      of more aromatic and higher-sized fractions. Spectrophotometric titrations were
      done to estimate changes of reactivity of supernatants from adsorption
      experiments made at pH ~6.8 and different PAHA concentrations. Evolutions of
      UV/Visible spectra with varying pH were treated to obtain titration curves that
      are interpreted within the NICA-Donnan framework. Protonation parameters of non
      sorbed PAHA fractions are compared to those obtained for the PAHA before contact
      with the oxide. The amount of low proton-affinity type of sites and the value of
      their median affinity constant decrease after adsorption. From PAHA concentration
      in the supernatant and mass balance calculations, "titration curves" are
      experimentally proposed for the adsorbed fractions for the first time. These
      changes in reactivity to our opinion could explain the difficulty to model the
      behavior of ternary systems composed of pollutants/HS/mineral since additivity is
      not respected.

PMID- 22154286
TI  - Early changes in apparent diffusion coefficient from diffusion-weighted MR
      imaging during radiotherapy for prostate cancer.
AB  - PURPOSE: To investigate the feasibility of diffusion-weighted MRI (DWI) as an
      early and reproducible change indicator in patients receiving radiotherapy for
      prostate cancer (PC). METHODS AND MATERIALS: Eight consecutive patients with
      biopsy-proven PC underwent DWI at 3T. All patients who received external-beam
      radiotherapy had four serial MR scans, as follows: before therapy (PreTx); after
      1 week of therapy (PostT1); after 3 weeks of therapy (PostT2); and 1 month after
      the completion of therapy (PostT3). At each time, the apparent diffusion
      coefficient (ADC) was measured in tumors and normal tissues. For reproducibility
      of the ADC measurement, five patients also had two separate pretreatment DWI
      scans at an interval of <2 weeks. Serum prostate-specific antigen (PSA) levels
      were evaluated at the same time as MR scans. RESULTS: Thirteen tumors (peripheral
      zone = 10; transition zone = 3) were found. The mean ADC values for the tumors
      from PreTx to PostT3 were 0.86, 1.03, 1.15, and 1.26 * 10(-3) mm(2)/s in
      sequence, respectively. Compared with PreTx, PostT1 (p = 0.005), PostT2 (p =
      0.003), and PostT3 (p < 0.001) showed a significant increase in ADC values. The
      mean ADC values of the benign tissues from PreTx to PostT3 were 1.60, 1.58, 1.47,
      and 1.46 * 10(-3) mm(2)/s in sequence, respectively. Reproducibility of ADC
      measurements was confirmed with a mean difference in ADC of -0.04 in peripheral
      zone and -0.017 in transition zone between two separate pretreatment MR scans.
      The mean PSA levels from PreTx to PostT3 were 9.05, 9.18, 9.25, and 4.11 ng/mL in
      sequence, respectively. CONCLUSIONS: DWI, as a reproducible biomarker, has the
      potential to evaluate the early therapeutic changes of PC to radiotherapy.

PMID- 22154287
TI  - [Upgrading to biventricular pacing for dilated cardiomyopathy following right
      ventricular pacing in a young patient].
AB  - A 2-day-old male infant required a conventional VVI pacemaker for congenital
      atrioventricular block. Three years later, he developed progressive heart failure
      due to left ventricular (LV) dysfunction and mitral regurgitation despite
      optimized medical treatment, and a cardiac resynchronization therapy (CRT) device
      was implanted. This is the first Portuguese report of CRT in a pediatric patient.
      One-year echocardiographic follow-up showed that LV shortening fraction had
      improved and LV end-diastolic dimension and mitral regurgitation had decreased.
      New York Heart Association class had improved from III-IV to I at 1-year follow
      up.

PMID- 22154288
TI  - Percutaneous revascularization strategies in saphenous vein graft lesions: long
      term results.
AB  - AIMS: Although half of saphenous vein grafts (SVGs) present obstructive
      atherosclerotic disease 10 years after implantation, controversy remains
      concerning the ideal treatment. Our aim was to compare percutaneous
      revascularization (PCI) options in SVG lesions, according to intervention
      strategy and type of stent. METHODS: A retrospective single-center analysis
      selected 618 consecutive patients with previous bypass surgery who underwent PCI
      between 2003 and 2008. Clinical and angiographic parameters were analyzed
      according to intervention strategy - PCI in SVG vs. native vessel vs. combined
      approach - and type of stent implanted - drug-eluting (DES) vs. bare-metal (BMS)
      vs. both. A Cox regressive analysis of event-free survival was performed with
      regard to the primary outcomes of death, myocardial infarction (MI) and target
      vessel failure (TVF). RESULTS: During a mean follow-up of 796+/-548 days the
      rates of death, MI and TVF were 10.9%, 10.5% and 29.5%, respectively. With regard
      to intervention strategy (74.4% of PCI performed in native vessels, 17.2% in SVGs
      and 8.4% combined), no significant differences were seen between groups (death
      p=0.22, MI p=0.20, TVF p=0.80). The type of stents implanted (DES 83.2%, BMS
      10.2%, both 3.2%) also did not influence long-term prognosis (death p=0.09, MI
      p=0.11, TVF p=0.64). The implantation of DES had a favorable impact on survival
      (p<0.001) in the subgroup of patients treated in native vessels but not in SVG.
      CONCLUSIONS: Among patients with SVG lesions, long-term mortality, MI and TVF
      were not affected by intervention options, except for the favorable impact on
      survival of DES in patients treated in native vessels.

PMID- 22154289
TI  - Left ventricular outflow tract obstruction and Takotsubo syndrome.

PMID- 22154291
TI  - [Dual-time point images of the liver with (18)F-FDG PET/CT in suspected
      recurrence from colorectal cancer].
AB  - AIM: To analyze the potential improvement of (18)F-fluorodeoxyglucose (FDG)
      PET/CT using additional delayed images of the liver in operated colorectal
      cancer. MATERIAL AND METHODS: The study prospectively included 71 patients (22
      women, 49 men) with mean age of 65 +/- 11 years with clinical, analytic or
      radiological suspicion of current disease. A whole body PET/CT scan was performed
      at 60 min. (standard images) and after 2 hr (delayed images) post-injection of
      4.07 MBq/Kg of (18)F-FDG. Visual and quantitative SUV analysis of PET/CT findings
      was done. All findings were confirmed by histopathology and/or at least 6 months
      follow-up. RESULTS: Thirty-seven out of 71 patients were diagnosed of liver
      metastases (79 metastases). In 38/71 cases there was extra-hepatic disease in the
      form of local recurrence (10), abdominopelvic (3) or mediastinal (3) lymph nodes,
      bone (1) or lung metastases (16) and carcinomatosis (10). Sensitivity and
      specificity in the diagnosis of liver metastases in a patient-by-patient basis in
      standard (81% and 91%) and in delayed images (95% y 97%) was calculated. The
      number of lesions detected in delayed images was significantly higher (66/79)
      than in standard images (57/79). Sensitivity and specificity for PET/CT in the
      diagnosis of extra-hepatic disease was 84% and 70%, contributing to the detection
      of synchronous tumors in 5 patients. CONCLUSIONS: PET/CT may be useful in the
      diagnosis of extra-hepatic disease in suspected recurrence of colorectal cancer.
      Delayed images on PET/CT may increase the sensitivity to identify liver
      metastases.

PMID- 22154292
TI  - Heavy metal-free 19F NMR probes for quantitative measurements of glutathione
      reductase activity using silica nanoparticles as a signal quencher.
AB  - For the quantitative assessment of the glutathione reductase (GR) activity with a
      (19)F NMR spectroscopy, we developed the heavy metal-free probes based on silica
      nanoparticles modified with water-soluble perfluorinated dendrimers via the
      disulfide linkers. Before enzymatic reaction, the molecular rotation of the
      perfluorinated dendrimers is highly restricted, and the magnitude of (19)F NMR
      signals from the perfluorinated dendrimers can be suppressed. By the reductive
      cleavage of the disulfide linkers with the reduced glutathione-mediated enzymatic
      reaction of GR, perfluorinated dendrimers can be released from the surfaces of
      the nanoparticles. Consequently, the (19)F NMR signals of perfluorinated
      dendrimers were recovered. The enzymatic activity of GR was determined from the
      increase of the magnitude of (19)F NMR signals. Finally, to demonstrate the
      feasibility of the probe in the presence of miscellaneous molecules under bio
      mimetic conditions, the comparison study was executed with the cancer cell
      lysate. The value determined from our method showed a good agreement with that
      from the conventional method.

PMID- 22154293
TI  - Studies of anti-fibrillogenic activity of phthalocyanines of zirconium containing
      out-of-plane ligands.
AB  - Series of phthalocyanines of zirconium containing lysine, citric, nonanoic acid
      residues and dibenzolylmethane groups as out-of-plane ligands are firstly studied
      as inhibitors of fibrillogenesis using cyanine-based fluorescent inhibitory
      assay. It was shown that studied phthalocyanines at concentration of 20MUM
      inhibited aggregation reaction on 38.5-57.6% and inhibitory activity of
      phthalocyanines depended on the chemical nature of out-of-plane ligand. For the
      most active compound PcZrLys(2) (zirconium phthalocyanine containing lysine
      fragment) the efficient inhibitor concentration was estimated to be 37MUM. AFM
      studies have shown that in the presence of PcZrLys(2) the inhibition of fibrils
      formation and formation of spherical oligomeric aggregates took place. Due to the
      ability of phthalocyanines to decrease efficiently protein aggregation into the
      amyloid fibrils, modification of phthalocyanine molecules via out-of-plane
      substitutions was proposed as approach for design of anti-fibrillogenic agents
      with required properties.

PMID- 22154294
TI  - Layer-by-Layer coated tyrosinase: An efficient and selective synthesis of
      catechols.
AB  - Agaricus bisporous tyrosinase was immobilized on commercial available epoxy-resin
      Eupergit(r)C250L and then coated by the Layer-by-Layer method (LbL). The two
      novel heterogeneous biocatalysts were characterized for their morphology, pH and
      storage stability, kinetic properties (K(m), V(max), V(max)/K(m)) and
      reusability. These biocatalysts were used for the efficient and selective
      synthesis of bioactive catechols under mild and environmental friendly
      experimental conditions. Ascorbic acid was added in the reaction medium to
      inhibit the formation of ortho-quinones, thus avoiding the known enzyme suicide
      inactivation process. Catechols were obtained mostly in quantitative yields and
      conversion of substrate. Tyrosinase immobilized on Eupergit(r)C250L and coated by
      the LbL method showed better catalytic activities, higher pH and storage
      stability, and reusability with respect to immobilized uncoated tyrosinase. Since
      chemical procedures to synthesize catechols are often expensive and with high
      environmental impact, the use of immobilized tyrosinase represents an efficient
      alternative for the preparation of this family of bioactive compounds.

PMID- 22154295
TI  - Madelung's disease.

PMID- 22154296
TI  - Restless legs syndrome in Chinese elderly people of an urban suburb in Shanghai:
      a community-based survey.
AB  - OBJECTIVE: The aim of the study is to investigate the prevalence rate of restless
      legs syndrome (RLS) in elderly Chinese people over 50 years of age in an urban
      suburb of Shanghai by a community-based study. METHODS: A 3-step survey was
      adopted including two telephone-based interviews and one face-to-face interview.
      We used questions based on four diagnostic criteria for RLS to perform the first
      telephone interview. The second telephone interview was performed by a sleep
      specialist to rule out the 'mimics' and secondary RLS. The final face-to-face
      interview was performed in the clinic for confirmation and examination. RESULTS:
      There were 2609 inhabitants in the Wuli Bridge suburb of Shanghai who responded
      to the first telephone interview (men 68.55+/-10.13 years of age and women
      65.34+/-10.52 years of age, mean+/-SD). Eighteen people were finally diagnosed
      with RLS. In this sample, the overall prevalence rate of RLS was about 0.69% (95%
      confidence interval (CI): 0.41-1.09). CONCLUSION: Our study provided the first
      data about the prevalence rate of RLS in an urban suburb of Shanghai from
      mainland China, which is consistent with the low prevalence rate reported in
      other Asian countries.

PMID- 22154297
TI  - Albert Schweitzer: a patient with writer's cramp.
AB  - Albert Schweitzer (1875-1965) the world-famous philosopher, theologian, concert
      organist, musicologist, philanthropist and winner of the 1952 Nobel Peace Prize
      suffered throughout most of his life from severe and painful muscle cramps in his
      right upper extremity which were triggered exclusively by handwriting. They led
      to tonic finger flexion and wrist extension and produced slow and clumsy
      handwriting of a reduced character size. Other motor functions including
      Schweitzer's highly skilful and famous organ playing were not affected.
      Inheritance from his mother is likely. Schweitzer applied several coping
      strategies including a specific holding pattern for pens, usage of special pens,
      avoidance of handwriting and slowing of handwriting. With all these features
      Schweitzer presents as a classical case of action-specific dystonia in the form
      of a simple tonic writer's cramp. Interestingly, Schweitzer never received a
      medical diagnosis, although writer's cramp had already been identified and
      described as a medical condition. Impairment of his handwriting but not his organ
      playing may give insight into the multifactorial aetiology of writer's cramp.

PMID- 22154298
TI  - First neuropathological description of a patient with Parkinson's disease and
      LRRK2 p.N1437H mutation.
AB  - The c.4309A>C mutation in the LRRK2 gene (LRRK2 p.N1437H) has recently been
      reported as the seventh pathogenic LRRK2 mutation causing monogenic Parkinson's
      disease (PD). So far, only two families worldwide have been identified with this
      mutation. By screening DNA from seven brains of PD patients, we found one
      individual with seemingly sporadic PD and LRRK2 p.N1437H mutation. Clinically,
      the patient had levodopa-responsive PD with tremor, and developed severe motor
      fluctuations during a disease duration of 19 years. There was severe and painful
      ON-dystonia, and severe depression with suicidal thoughts during OFF. In the
      advanced stage, cognition was slow during motor OFF, but there was no noticeable
      cognitive decline. There were no signs of autonomic nervous system dysfunction.
      Bilateral deep brain stimulation of the subthalamic nucleus had unsatisfactory
      results on motor symptoms. The patient committed suicide. Neuropathological
      examination revealed marked cell loss and moderate alpha-synuclein positive Lewy
      body pathology in the brainstem. There was sparse Lewy pathology in the cortex. A
      striking finding was very pronounced ubiquitin-positive pathology in the
      brainstem, temporolimbic regions and neocortex. Ubiquitin positivity was most
      pronounced in the white matter, and was out of proportion to the comparatively
      weaker alpha-synuclein immunoreactivity. Immunostaining for tau was mildly
      positive, revealing non-specific changes, but staining for TDP-43 and FUS was
      entirely negative. The distribution and shape of ubiquitin-positive lesions in
      this patient differed from the few previously described patients with LRRK2
      mutations and ubiquitin pathology, and the ubiquitinated protein substrate
      remains undefined.

PMID- 22154299
TI  - Co-production of ethanol, biogas, protein fodder and natural fertilizer in
      organic farming--evaluation of a concept for a farm-scale biorefinery.
AB  - The addition of a biorefinery to an organic farm was investigated, where ethanol
      was produced from germinated rye grains and whey, and the effluent was separated
      into two streams: the protein-rich solid fraction, to be used as animal feed, and
      the liquid fraction, which can be co-digested with clover grass silage to produce
      biogas. A method for ethanol production from rye was applied by utilizing
      inherent amylase activity from germination of the seed. Biogas potential of
      ethanol fermentation effluent was measured through anaerobic digestion trials.
      The effluent from the trials was assumed to serve as natural fertilizer. A
      technoeconomic analysis was also performed; total capital investment was
      estimated to be approximately 4 M USD. Setting a methane selling price according
      to available incentives for "green electricity" (0.72 USD/m(3)) led to a minimum
      ethanol selling price of 1.89 USD/L (project lifetime 25 yr, at a discount rate
      10%).

PMID- 22154300
TI  - Critical cellulase and hemicellulase activities for hydrolysis of ionic liquid
      pretreated biomass.
AB  - Critical cellulase and hemicellulase activities are identified for hydrolysis of
      ionic liquid (IL) pretreated poplar and switchgrass; hemicellulase rich
      substrates with largely amorphous cellulose. Enzymes from Aspergillus nidulans
      were expressed and purified: an endoglucanase (EG) a cellobiohydrolase (CBH), an
      endoxylanase (EX) and an acetylxylan esterase (AXE). beta-Xylosidase (betaX) from
      Selenomonas ruminantium and a commercial beta-glucosidase (betaG) from Novozyme
      188 were admixed with the A. nidulans enzymes. Statistical analysis indicates
      that betaG and betaX activities are significant for both glucose and xylose
      yields for the two substrates. EG is a significant factor for glucan hydrolysis
      while EX is significant for xylan hydrolysis of the substrates. The CBH, which
      has activity on crystalline cellulose and negligible activity on amorphous
      cellulose, was not a significant factor in glucan hydrolysis. EX is significant
      in glucan hydrolysis for poplar. The addition of AXE significantly improves xylan
      hydrolysis for poplar but not switchgrass.

PMID- 22154301
TI  - MDR-1-overexpression in HT 29 colon cancer cells grown in SCID mice.
AB  - The multidrug-resistance 1 (MDR-1) P-glycoprotein (Pgp) is a transmembrane
      transporter system, which actively pumps cytotoxic drugs out of the cell. MDR-1
      acquired in vitro differs from MDR-1 acquired in vivo, but has important
      consequences on the cellular phenotype and metastatic behavior. Here we report
      that the human colonic cancer cell line HT29 (MDR-1 negative) is more malignant
      than its MDR-1 overexpressing variant (HT29 MDR-1 positive). HT29 MDR-1 negative
      cells produce undifferentiated signet ring carcinomas when implanted
      subcutaneously into SCID mice, while HT29 MDR-1 positive cells form tumors with
      tubular structures, but without signet ring cells. Immunohistochemical
      proliferation marker analysis revealed that the MDR-1 positive cells proliferate
      much more slowly than the MDR-1 negative cells. MDR-1 overexpression results in a
      less differentiated phenotype at the cellular level (absence of mucin producing
      cells) but in a more differentiated phenotype at the tissue level (tubule
      formation). In addition, lectin binding patterns including that of Helix pomatia
      agglutinin (HPA), an indicator of metastatic potential, differed between the two
      cell lines. HT29 MDR-1 positive cells had less HPA binding sites than HT29 MDR-1
      negative counterparts and metastasized less frequently in SCID mice. As slow
      proliferation, low degree of differentiation and multidrug-resistance is a
      hallmark of cancer stem cells and all were present in MDR-1 positive tumors, it
      is attractive to speculate that they represent a stem cell rich tumor. As shown
      by global gene expression analyses, genes involved, e.g. in cell adhesion,
      glycosylation and signal transduction, were deregulated in MDR-1 positive tumors
      compared to MDR-negative tumors. Overexpression of E-cadherin and
      carcinoembryonic antigen-related cell adhesion molecules 1 (CEACAM1) may provide
      clues to the mechanisms responsible for the reduced metastatic potential of MDR-1
      overexpressing tumors. Since drug treatment shifted the cells towards a less
      metastatic phenotype in this in vivo model, it seems conceivable to achieve this
      using drug treatment also in a clinical situation.

PMID- 22154303
TI  - Effect of hypothermia on coagulatory function and survival in Sprague-Dawley rats
      exposed to uncontrolled haemorrhagic shock.
AB  - BACKGROUND: Acute coagulopathy, hypothermia, and acidosis are the lethal triad of
      conditions manifested by major trauma patients. Recent animal studies have
      reported that hypothermia improves survival in animals subjected to controlled
      haemorrhagic shock. The objective of this study was to investigate the effect of
      hypothermia on coagulation in rats subjected to uncontrolled haemorrhagic shock.
      METHODS: Thirty-two male Sprague-Dawley rats were randomly divided into four
      groups: normothermia (control, group N), hypothermia (group H), hypothermic
      haemorrhagic shock (group HS), and normothermic haemorrhagic shock (group NS).
      Haemorrhagic shock was induced by splenic laceration. Capacity for coagulation
      was measured by rotation thromboelastometry (ROTEM((r))), and was measured at
      baseline as well as the end of the shock and resuscitation periods. Survival was
      observed for 48 h post-trauma. RESULTS: Baseline parameters were not different
      amongst the groups. Rats exposed to hypothermia alone did not differ in
      coagulation capacity compared to the control group. Clot formation time (CFT) and
      maximal clot firmness (MCF) in group HS decreased as the experiment progressed.
      Maximal clot firmness time (MCFt) in groups H and HS was significantly prolonged
      during shock and resuscitation compared with that in group NS. In group NS, MCF
      did not change significantly, but MCFt was reduced compared with baseline. Group
      HS had poor survival when compared with normovolaemic groups. CONCLUSION: Blood
      clotted less firmly in traumatic haemorrhagic shock, and hypothermia prolonged
      clotting. However, clot firmness maximised rapidly under normothermic
      haemorrhagic shock. Haemorrhage would continue for a longer time in hypothermic
      haemorrhagic shock. Survival of hypothermic shock was not significantly different
      compared to that of normothermic haemorrhagic shock.

PMID- 22154302
TI  - Long-term and within-day variability of working memory performance and EEG in
      individuals.
AB  - OBJECTIVE: Assess individual-subject long-term and within-day variability of a
      combined behavioral and EEG test of working memory. METHODS: EEGs were recorded
      from 16 adults performing n-back working memory tasks, with 10 tested in morning
      and afternoon sessions over several years. Participants were also tested after
      ingesting non-prescription medications or recreational substances. Performance
      and EEG measures were analyzed to derive an Overall score and three constituent
      sub-scores characterizing changes in performance, cortical activation, and
      alertness from each individual's baseline. Long-term and within-day variability
      were determined for each score; medication effects were assessed by reference to
      each individual's normal day-to-day variability. RESULTS: Over the several year
      period, the mean Overall score and sub-scores were approximately zero with
      standard deviations less than one. Overall scores were lower and their
      variability higher in afternoon relative to morning sessions. At the group level,
      alcohol, diphenhydramine and marijuana produced significant effects, but there
      were large individual differences. CONCLUSIONS: Objective working memory measures
      incorporating performance and EEG are stable over time and sensitive at the level
      of individual subjects to interventions that affect neurocognitive function.
      SIGNIFICANCE: With further research these measures may be suitable for use in
      individualized medical care by providing a sensitive assessment of incipient
      illness and response to treatment.

PMID- 22154304
TI  - Fractures of the neck of the fifth metacarpal bone. Medium-term results in 28
      cases treated by percutaneous transverse pinning.
AB  - The purpose of this study was to report the medium-term results in 28 patients
      affected by closed displaced fractures of the neck of the fifth metacarpal bone
      (boxer's fracture) with an associated severe swelling of the hand, who were
      treated with percutaneous transverse K-wire pinning, to verify the effectiveness
      of this surgical treatment. We opted for this treatment in all cases in which
      malrotation of the fifth finger and volar angulation of the metacarpal head
      greater than 30 degrees  were associated with a severe swelling of the hand. All
      the patients were reviewed clinically and radiologically at an average of 25
      months after surgery. At the final follow-up, no patient reported residual pain.
      All patients had full extension of the fifth finger, except two in whom we
      observed a limitation of the extension of the fifth metacarpophalangeal (MP)
      joint of about 10 degrees , without significant impairment of hand function. All
      patients had at least 90 degrees  flexion of the fifth MP joint and full range of
      motion of the interphalangeal (IP) joints. No patient had rotational deformity of
      the fifth finger with a deficit of grip strength. At the final follow-up, a
      residual palmar angulation of the head of the fifth metacarpal was found in three
      patients, with a mean of 7 degrees . The disabilities of the arm, shoulder and
      hand (DASH) scale had a mean value of 5, and all patients considered their result
      as good or excellent. We recommend percutaneous transverse pinning in all boxer's
      fractures in which operative treatment is indicated, especially in patients with
      severe soft-tissue swelling. The surgical procedure is easy to perform, and
      surgical results are generally good.

PMID- 22154305
TI  - Hexavalent chromium reduction by an actinobacterium Flexivirga alba ST13T in the
      family Dermacoccaceae.
AB  - An isolated strain Flexivirga alba ST13(T) was examined for the reducing activity
      of hexavalent chromium (Cr(VI)). Strain ST13(T) grew in the liquid medium
      containing 0.33 mM Cr(VI) under aerobic cultivation, even though growth was
      inhibited on agar minimal media containing 0.31 mM Cr(VI). The growth in the
      liquid medium containing Cr(VI) at 3 mM was severely inhibited, and the
      concentration of Cr(VI) decreased below the detection limit within 13 days. Most
      of the Cr(VI) was eliminated from the liquid medium in the log phase and the
      stationary phase. XANES analysis of the precipitate shows the presence of
      Cr(OH)(3), indicating the bacterial reduction of Cr(VI) to trivalent chromium
      (Cr(III)). The bacterial Cr(VI) reduction was more efficient in minimal medium
      supplemented with molasses than with glucose. These results strongly suggest that
      the isolate F. alba ST13(T) is a novel actinobacterium with Cr(VI) reducing
      activity that is stimulated by molasses.

PMID- 22154306
TI  - A biomechanical comparison of multidirectional nail and locking plate fixation in
      unstable olecranon fractures.
AB  - BACKGROUND: The main theoretic advantage of proximal olecranon fracture
      intramedullary fixation is decreased soft-tissue irritation and, potentially,
      less subsequent hardware removal. Despite this possible benefit, questions remain
      as to whether intramedullary devices are capable of controlling olecranon
      fractures to the same extent as locking plates. This study evaluates the ability
      of a novel multidirectional locking nail to stabilize comminuted fractures and
      directly compares its biomechanical performance with that of locking olecranon
      plates. MATERIALS AND METHODS: We implanted 8 stainless steel locking plates and
      stainless steel intramedullary nails to stabilize a simulated comminuted fracture
      in 16 fresh-frozen cadaveric elbows. Flexion-extension, varus-valgus, gap
      distance, and rotational 3-dimensional angular displacement analysis was
      conducted over a 60 degrees  motion arc (30 degrees  to 90 degrees ) to assess
      fragment motion through physiologic cyclic arcs of motion and failure loading.
      Displacements in all planes were compared. RESULTS: Both implants showed less
      than 1 degrees  of motion in all measured planes and allowed less than 1 mm of
      gapping through all loads tested until ultimate failure. All failures occurred by
      sudden, catastrophic means. The mean failure weight for the nail was 14.4 kg
      compared with 8.7 kg for the plate (P = .02). The nail survived 1102 cycles,
      whereas the plate survived 831 cycles (P = .06). CONCLUSION: In simulated
      comminuted olecranon fractures, the multidirectional locking intramedullary nails
      sustained significantly higher maximum loads than the locking plates. The two
      implants showed no significant differences in fragment control or number of
      cycles survived. Surgeons can expect the multidirectional locking nails to
      stabilize comminuted fractures at least as well as locking plates.

PMID- 22154307
TI  - A vascularized scapular graft for juvenile osteonecrosis of the humeral head.

PMID- 22154308
TI  - Surgical management of uncomplicated midshaft clavicle fractures: a comparison
      between titanium elastic nails and small reconstruction plates.
AB  - BACKGROUND: This study compared titanium elastic nail (TEN) fixation with plate
      fixation in patients with uncomplicated midshaft clavicle fractures. METHODS: The
      records of 57 patients with midshaft clavicular fractures that were operated on
      within 2 weeks after injury at Kaohsiung Veterans General Hospital, Kaohsiung
      City, Taiwan, were retrospectively analyzed. Each patient received either TENs (n
      = 25) or fixation with a 3.5-mm reconstruction plate (n = 32) depending on the
      preference of the operating surgeon. Operative parameters, postoperative pain and
      function scores, complications, and fracture union time were determined. RESULTS:
      There was no difference in the fracture pattern distribution between the 2
      groups, and all operations were performed without complications. Operation time,
      wound size, blood loss, length of hospitalization, and subjective time to pain
      relief were less for the TEN group than for the 3.5-mm reconstruction plate
      fixation group (P < .001 for all). Patients in the TEN group showed a greater
      range of shoulder motion and higher Constant scores than those in the plate
      fixation group up to 18 weeks after surgery (P < .001 for all). Fewer patients in
      the TEN group, 4 (16%), requested removal of the implant, as compared with 12
      (37.5%) in the plate group. CONCLUSION: Fixation of uncomplicated midshaft
      clavicle fractures with TENs provides adequate fixation and faster relief of pain
      and return to normal function of the affected shoulder than fixation with 3.5-mm
      reconstruction plates.

PMID- 22154309
TI  - Recovery of sensory disturbance after arthroscopic decompression of the
      suprascapular nerve.
AB  - BACKGROUND: The existence of sensory branches of the suprascapular nerve (SSN)
      has recently been reported, and sensory disturbance at the lateral and posterior
      aspect of the shoulder has been focused on as a symptom of SSN palsy. We have
      performed arthroscopic release of SSN at the suprascapular notch in patients with
      sensory disturbance since 2006. The purposes of this study were to introduce the
      arthroscopic surgical technique and investigate postoperative recovery of sensory
      disturbance. MATERIALS AND METHODS: The study included 11 men and 14 women (25
      shoulders), with an average age of 63.9 years (range, 41-77 years). Arthroscopic
      decompression of the SSN was performed using a suprascapular nerve (SN) portal as
      a landmark for approaching the suprascapular notch. Sensory disturbance of the
      shoulder was evaluated preoperatively and postoperatively. The average follow-up
      was 18.5 months (range, 12-30 months). RESULTS: The arthroscopic procedures were
      performed safely. The preoperative sensory disturbance fully recovered
      postoperatively in all shoulders. CONCLUSION: Arthroscopic release of the SSN is
      a useful procedure for SSN entrapment at the suprascapular notch. The sensory
      disturbance at the lateral and posterior aspect of the shoulder can be used as
      one of the criteria of diagnosing SSN palsy, especially in shoulders with massive
      rotator cuff tear, in which diagnosing and assessing the treatment results of
      associated SSN palsy is usually difficult.

PMID- 22154310
TI  - Periprosthetic infections after shoulder hemiarthroplasty.
AB  - BACKGROUND: To examine the rates and predictors of deep periprosthetic infections
      after shoulder hemiarthroplasty. METHODS: We used prospectively collected
      institutional registry data on all primary shoulder hemiarthroplasty patients
      from 1976-2008. We estimated survival free of deep periprosthetic infections
      using Kaplan-Meier survival curves. Using univariate Cox regression analyses, we
      examined the association of patient-related factors (age, sex, body mass index),
      comorbidity (Deyo-Charlson index), American Society of Anesthesiologists grade,
      underlying diagnosis, and implant fixation with the risk of infection. RESULTS: A
      total of 1,349 patients, with a mean age of 63 years (SD, 16 years), 63% of whom
      were women, underwent 1,431 primary shoulder hemiarthroplasties. Mean follow-up
      was 8 years (SD, 7 years). Fourteen deep periprosthetic infections occurred
      during the follow-up, confirmed by medical record review. The most common
      organisms were Staphylococcus aureus, coagulase-negative Staphylococcus, and
      Propionibacterium acnes, each accounting for 3 cases (21% each). The 5-, 10-, and
      20-year prosthetic infection-free rates were 98.9% (95% confidence interval [CI],
      98.3%-99.5%), 98.7% (95% CI, 98.1%-99.4%), and 98.7% (95% CI, 98.1%-99.4%),
      respectively. None of the factors evaluated were significantly associated with
      risk of prosthetic infection after primary shoulder hemiarthroplasty, except that
      an underlying diagnosis of trauma was associated with a significantly higher
      hazard ratio of 3.18 (95% CI, 1.06-9.56) for infection compared with all other
      diagnoses (P = .04). A higher body mass index showed a non-statistically
      significant trend toward an association with higher hazard (P = .13). CONCLUSION:
      The periprosthetic infection rate after shoulder hemiarthroplasty was low,
      estimated at 1.3% at 20-year follow-up. An underlying diagnosis of trauma was
      associated with a higher risk of periprosthetic infection. These patients should
      be observed closely for development of infection.

PMID- 22154311
TI  - Open debridement and radiocapitellar replacement in primary and post-traumatic
      arthritis of the elbow: a multicenter study.
AB  - BACKGROUND: Postmortem and clinical studies have shown an early and prevalent
      involvement of the radiohumeral joint in primary and secondary arthritis of the
      elbow. The lateral resurfacing elbow (LRE) prosthesis has recently been developed
      for the treatment of lateral elbow arthritis. However, few data have been
      published on LRE results. MATERIALS AND METHODS: A prospective multicenter study
      was designed to assess LRE preliminary results. There were 20 patients (average
      age, 55 years). Preoperative diagnosis were primary osteoarthritis in 11 and post
      traumatic osteoarthritis in 9. All patients underwent open debridement and LRE
      prosthesis. Patients were evaluated preoperatively and postoperatively with the
      Mayo Elbow Performance Score (MEPS), modified American Shoulder Elbow Surgeons (m
      ASES) elbow assessment, and the Quick Disabilities of the Arm, Shoulder and Hand
      (Quick-DASH). Mean follow-up was 22.6 months. RESULTS: At the last follow-up, the
      mean improvement of MEPS and m-ASES was 35 (P = .001) and 34 (P = .001)
      respectively; the average Quick DASH decreased by 29 (P = .001). Average range of
      motion was improved by 35 degrees  (P = .001). MEPI results were excellent in 12
      patients, good in 2, and fair and poor in 3 each. Mild overstuffing was observed
      in 5 patients, and an implant malpositioning in 3. The implant survival rate was
      100%. CONCLUSION: LRE showed promising results in this prospective investigation.
      Most patients had an uneventful postoperative course and have shown a painless
      elbow joint, with satisfactory functional recovery at short-term follow-up.
      Further studies with longer follow-up are warranted.

PMID- 22154312
TI  - Antibiotic-loaded bone cement reduces deep infection rates for primary reverse
      total shoulder arthroplasty: a retrospective, cohort study of 501 shoulders.
AB  - BACKGROUND: Deep infection after primary reverse total shoulder arthroplasty is a
      devastating event and has an increased incidence compared with anatomic total
      shoulder arthroplasty. Recent reports in the hip and knee arthroplasty literature
      suggest that antibiotic-loaded bone cement may lower infection rates for primary
      arthroplasties. We conducted a retrospective cohort study to evaluate the effect
      of antibiotic-loaded bone cement vs plain bone cement on the prevention of deep
      infection after primary reverse total shoulder arthroplasty. MATERIALS AND
      METHODS: Four surgeons from their respective facilities participated in the
      retrospective cohort data collection. From 1999 to 2008, 501 consecutive primary
      reverse total shoulder arthroplasties were performed. Patients with revision of
      failed previous arthroplasties were excluded, and patients with any other
      previous shoulder procedure were included. Two groups were examined in this
      retrospective cohort: In group 1 (265 shoulders), the cement used for humeral
      fixation did not have antibiotics; in group 2 (236 shoulders), antibiotic
      impregnated bone cement containing tobramycin, gentamycin, or
      vancomycin/tobramycin was used for fixation. RESULTS: At an average postoperative
      follow-up of 37 months, no deep infection had developed in the 236 shoulders in
      group 2, whereas a deep infection had developed in 8 of the 265 shoulders (3.0%)
      in group 1. This difference between the groups was significant (P < .001).
      CONCLUSIONS: Antibiotic-impregnated bone cement was effective in the prevention
      of postoperative deep infection after primary reverse total shoulder arthroplasty
      during short-term follow-up.

PMID- 22154313
TI  - Pattern and time phase of shoulder function and power recovery after arthroscopic
      rotator cuff repair.
AB  - BACKGROUND: It has been our observation that early during rehabilitation after
      rotator cuff repair, patients may take a step back before improving. The purpose
      of this study is to investigate the pattern and time phase of changes in Constant
      score and strength recovery after arthroscopic rotator cuff repair. MATERIALS AND
      METHODS: Forty-five patients undergoing arthroscopic rotator cuff repair were
      prospectively enrolled in this study. Patients underwent scoring preoperatively
      with the Constant score. All were followed up at 3 months and 6 months after
      surgery. The Constant score and strength at 3 months were compared with those at
      the 6-month mark. RESULTS: The mean Constant score improved from 46.4 points (SD,
      17.3) preoperatively to 51.8 points (SD, 13.5) 3 months postoperatively (P =
      .0777). At 6 months postoperatively, the mean Constant score was 69.0 points (SD,
      11.1), a significant increase from both the preoperative (P < .0001) and 3-month
      (P < .0001) results. The mean preoperative strength result of 4.5 kg (SD, 3.2)
      decreased significantly to 3.3 kg (SD, 1.8) at 3 months postoperatively (P =
      .0154) before improving to 5.8 kg (SD, 2.6) at 6 months postoperatively. The
      improvement in strength at 6 months was significant compared with both the
      preoperative (P = .0070) and 3-month (P < .0001) results. CONCLUSIONS: Although
      there is highly significant improvement in overall function (Constant score) and
      strength 6 months postoperatively, patients appear to take a step back before
      improving, in fact with a drop in strength at 3 months. This may cause concern in
      patients and may require assurance that time and effort with physiotherapy will
      improve function and symptoms.

PMID- 22154314
TI  - Renal function assessed using cystatin C and antiplatelet efficacy of clopidogrel
      assessed using the vasodilator-stimulated phosphoprotein index in patients having
      percutaneous coronary intervention.
AB  - Renal dysfunction is a strong independent predictor of stent thrombosis. The aim
      of the present study was to evaluate the strength and direction of the
      association between kidney function and clopidogrel efficacy. The study group
      consisted of consecutive patients (n = 275) who underwent stent implantation.
      Drug efficacy was measured using the vasodilator-stimulated phosphoprotein (VASP)
      index 20 +/- 4 hours after clopidogrel 600 mg. Nonresponse was defined as an VASP
      index >=50%. Renal function was determined using serum cystatin C. The upper
      reference levels are 1.12 mg/L for <=65 years of age and 1.21 mg/L for >65 years
      of age. Estimated glomerular filtration was calculated using cystatin C. The
      median value of cystatin C was 1.16 mg/L (twenty-fifth and seventy-fifth
      percentiles 0.96 and 1.43); 47.63% of the study population had cystatin C above
      reference levels and 33.1% of patients were nonresponders to clopidogrel. No
      correlation was found between clopidogrel efficacy assessed with the VASP index
      and kidney function assessed with cystatin C (Spearman r = -0.070, p = 0.248).
      Based on cystatin C the proportion of nonresponders to clopidogrel was 34.4%
      versus 31.9% (p = 0.702) in patients with impaired renal function compared to
      normal renal function, respectively. The proportion of clopidogrel nonresponders
      did not differ (p = 0.902) among groups with normal (28.8%), mildly impaired
      (34.8%), moderately impaired (32.9%), and severely impaired (34.8%) renal
      function. In conclusion, renal function assessed by cystatin C does not predict
      clopidogrel efficacy. Renal dysfunction is a complex entity and its significant
      relation to stent thrombosis cannot be explained simply by a decrease in
      clopidogrel efficacy.

PMID- 22154315
TI  - Comparison of benefit and mortality of implantable cardioverter-defibrillator
      therapy in patients aged >=75 years versus those <75 years.
AB  - Implantable cardioverter-defibrillator (ICD) therapy decreases arrhythmic and all
      cause mortality in patients at high risk of sudden death. However, its clinical
      benefit in elderly patients is uncertain. The aim of this study was to assess the
      long-term efficacy of ICD treatment in elderly patients and to identify markers
      of successful ICD therapy and risk factors of mortality. We performed
      multivariate analysis of a prospective long-term database from 2 tertiary care
      centers including 936 consecutive patients with an ICD. Predictors of ICD therapy
      and risk factors for mortality were assessed in patients >=75 years old at ICD
      implantation compared to younger patients. Mean follow-up time was 43 +/- 40
      months. Rates of ICD therapy were similar in the 2 age groups. No significant
      predictors of ICD therapy could be identified in older patients. Median estimated
      survival was 132 months in patients <75 years and 81 months in those >=75 years
      old (p = 0.006). Decreased ejection fraction (hazard ratio 1.62 per 10% decrease,
      p = 0.03) and impaired renal function (hazard ratio 1.57 per 10 ml/kg/m(2)
      decrease in estimated glomerular filtration rate, p = 0.02) were independent risk
      factors of mortality in patients >=75 years old. However, mortality of older
      patients was similar to that of the age-matched general population irrespective
      of delivery of ICD therapy. In conclusion, ICD therapy is effective for treatment
      of life-threatening arrhythmias in all age groups. However, prevention of sudden
      cardiac death may have limited impact on overall mortality in older patients.
      Despite a similar rate of appropriate ICD therapies, risk of death is increased
      1.6-fold in ICD recipients >=75 years old compared to younger patients. Patients
      with decreased ejection fraction and impaired renal function are at highest risk.

PMID- 22154316
TI  - Age modification of the association of lipoprotein, lipid, and lipoprotein ratio
      with carotid intima-media thickness (from the Multi-Ethnic Study of
      Atherosclerosis [MESA]).
AB  - Multiple studies have demonstrated an age-related attenuation in risk
      associations of lipoproteins and lipoprotein ratios with cardiovascular disease
      events. We recently reported a similar age-related attenuation in risk
      associations of lipoproteins and lipoprotein ratios with coronary artery calcium.
      We assessed risk associations of lipoproteins and lipoprotein ratios with carotid
      intima-media thickness (CIMT), which has not been reported previously. We
      performed multivariable linear regression using data from the Multi-Ethnic Study
      of Atherosclerosis (MESA). MESA participants were community-dwelling adults 45 to
      84 years of age without clinically apparent cardiovascular disease at baseline,
      and 4,961 met inclusion criteria for these analyses. In fully adjusted models,
      differences in CIMT were similar across the MESA age spectrum, with differences
      in internal CIMT per SD increase in low-density lipoprotein of 0.037 mm (95%
      confidence interval 0.018 to 0.055) for those 45 to 54 years old and 0.087 mm
      (95% confidence interval 0.027 to 0.146) for those 75 to 84 years old (p for
      interaction = 0.2). Similarly, the difference in internal CIMT per SD increase in
      the total/high-density lipoprotein cholesterol ratio was 0.029 mm (95% confidence
      interval 0.009 to 0.049) for those 45 to 54 years old and 0.101 mm (95%
      confidence interval 0.033, 0.169) for those 75 to 84 years old (p for interaction
      = 0.03). In general, risk associations of lipoproteins and lipoprotein ratios
      were associated with similar differences in CIMT across all age categories. In
      conclusion, abnormal lipoproteins and lipoprotein ratios in middle-aged and older
      patients are powerful risk factors for early atherosclerosis as manifested by an
      increased CIMT.

PMID- 22154317
TI  - Predicting costs among medicare beneficiaries with heart failure.
AB  - Disease management programs that target patients with the highest risk of
      subsequent costs may help payers and providers control health care costs, but
      identifying these patients prospectively is challenging. We hypothesized that
      medical history and clinical data from a heart failure registry could be used to
      prospectively identify patients with heart failure most likely to incur high
      costs. We linked Medicare inpatient claims to clinical registry data for patients
      with heart failure and calculated total Medicare costs during the year after the
      index heart failure hospitalization. We defined patients as having high costs if
      they were in the upper 5% (>$76,500) of the distribution. We used logistic
      regression models to identify patient and clinical characteristics associated
      with high costs. Costs for 40,317 patients in the study varied widely. Patients
      in the upper 5% of the cost distribution incurred mean costs of $117,193 +/-
      55,550 during 1 year of follow-up compared to $17,086 +/- 17,792 for the lower
      cost group. Demographic and clinical characteristics associated with high costs
      included younger age and black race; history of anemia, chronic obstructive
      pulmonary disease, ischemic heart disease, diabetes mellitus, or peripheral
      vascular disease; serum creatinine level; and systolic blood pressure at
      admission. Mean 1-year Medicare costs for patients whom the model predicted would
      exceed the high-cost threshold were >2 times the costs for patients below the
      threshold. In conclusion, a model based on variables from clinical registries can
      identify a group of patients with heart failure who on average will incur higher
      costs in the first year after hospitalization.

PMID- 22154318
TI  - Effect of changing heart rate during treatment of hypertension on incidence of
      heart failure.
AB  - An elevated heart rate (HR) at rest at baseline is associated with an increased
      risk of incident heart failure (HF) and with greater cardiovascular event rates
      in patients with chronic HF. However, despite the high attributable risk of
      hypertension for HF, whether the in-treatment HR predicts incident HF in patients
      with treated hypertension has not been evaluated. The HR was evaluated on annual
      electrocardiograms from 9,024 patients with hypertension without HF who were
      treated with losartan- or atenolol-based regimens. During a mean follow-up of 4.7
      +/- 1.1 years, HF developed in 285 patients (3.2%). On multivariate Cox analyses
      adjusted for randomized treatment, the baseline risk factors for HF, baseline and
      in-treatment blood pressure, QRS duration, and electrocardiographic left
      ventricular hypertrophy, a greater in-treatment HR predicted a 45% greater
      adjusted risk of new HF for every 10-beats/min increase in the HR (95% confidence
      interval [CI] 34% to 57%) or a 159% greater risk of HF in patients with the
      persistence or development of a HR of >=84 beats/min (95% CI 88% to 257%). In
      contrast, with adjustment for the same covariates, the baseline HR as a
      continuous variable was a significantly less powerful predictor of new HF (hazard
      ratio 1.15 per 10 beats/min, 95% CI 1.03 to 1.28) and a baseline HR of >=84
      beats/min did not predict new HF (hazard ratio 1.00, 95% CI 0.63 to 1.58). In
      conclusion, a greater in-treatment HR on the serial electrocardiograms predicts a
      greater risk of incident HF during antihypertensive treatment, independent of the
      covariates, in patients with hypertension with electrocardiographic left
      ventricular hypertrophy. These findings support serial HR assessment to improve
      the risk stratification of patients with hypertension.

PMID- 22154319
TI  - Parental intermittent claudication as risk factor for claudication in adults.
AB  - Little is known about the familial aggregation of intermittent claudication (IC).
      Our objective was to examine whether parental IC increased the risk of IC in
      adult offspring, independent of the established cardiovascular risk factors. We
      evaluated the Offspring Cohort Participants of the Framingham Heart Study who
      were >=30 years old, cardiovascular disease free, and had both parents enrolled
      in the Framingham Heart Study (n = 2,970 unique participants, 53% women). Pooled
      proportional hazards regression analysis was used to examine whether the 12-year
      risk of incident IC in offspring participants was associated with parental IC,
      adjusting for age, gender, diabetes, smoking, systolic blood pressure, total
      cholesterol, high-density lipoprotein cholesterol, and antihypertensive and lipid
      treatment. Of the 909 person-examinations in the parental IC history group and
      5,397 person-examinations in the no-parental IC history group, there were 101
      incident IC events (29 with parental IC history and 72 without a parental IC
      history) during follow-up. The age- and gender-adjusted 12-year cumulative
      incidence rate per 1,000 person-years was 5.08 (95% confidence interval [CI] 2.74
      to 7.33) and 2.34 (95% CI 1.46 to 3.19) in participants with and without a
      parental IC history. A parental history of IC significantly increased the risk of
      incident IC in the offspring (multivariable adjusted hazard ratio 1.81, 95% CI
      1.14 to 2.88). The hazard ratio was unchanged, with an adjustment for the
      occurrence of cardiovascular disease (hazard ratio 1.83, 95% CI 1.15 to 2.91). In
      conclusion, IC in parents increases the risk of IC in adult offspring,
      independent of the established risk factors. These data suggest a genetic
      component of peripheral artery disease and support future research into genetic
      causes.

PMID- 22154320
TI  - Prevalence of, and barriers to, preventive lifestyle behaviors in hypertension
      (from a national survey of Canadians with hypertension).
AB  - Patients with hypertension are advised to lower their blood pressure to <140/90
      mm Hg through sustained lifestyle modification and/or pharmacotherapy. To
      describe the use of lifestyle changes for blood pressure control and to identify
      the barriers to these behaviors, the data from 6,142 Canadians with hypertension
      who responded to the 2009 Survey on Living With Chronic Diseases in Canada were
      analyzed. Most Canadians with diagnosed hypertension reported limiting salt
      consumption (89%), having changed the types of food they eat (89%), engaging in
      physical activity (80%), trying to control or lose weight if overweight (77%),
      quitting smoking if currently smoking (78%), and reducing alcohol intake if
      currently drinking more than the recommended levels (57%) at least some of the
      time to control their blood pressure. Men, those aged 20 to 44 years, and those
      with lower educational attainment and lower income were, in general, less likely
      to report engaging in lifestyle behaviors for blood pressure control. A low
      desire, interest, or awareness were commonly reported barriers to salt
      restriction, changes in diet, weight loss, smoking cessation, and alcohol
      reduction. In contrast, the most common barrier to engaging in physical activity
      to regulate blood pressure was the self-reported challenge of managing a
      coexisting physical condition or time constraints. In conclusion, programs and
      interventions to improve the adherence to lifestyle changes to treat hypertension
      may need to consider the identified barriers to lifestyle behaviors in their
      design.

PMID- 22154321
TI  - The scimitar syndrome confirmed by 320-slice computerized tomography.
AB  - Scimitar syndrome is a relatively rare variety of congenital heart disease
      characterized by partial or complete anomalous pulmonary venous connection of the
      right lung into the inferior vena cava. There are virtually no reports of the use
      of 320-slice computed tomography in establishing the diagnosis. The investigators
      present a case of scimitar syndrome confirmed by 320-slice computed tomography.

PMID- 22154322
TI  - Hemodynamic progression and outcome of asymptomatic aortic stenosis in primary
      care.
AB  - The prognostic relevance of a rapid rate of hemodynamic progression of aortic
      stenosis (AS) has been predominantly investigated in tertiary centers. We
      reviewed the clinical and echocardiographic data from 153 asymptomatic patients
      with AS (age 77 +/- 9 years; 65% men), with normal left ventricular function and
      paired echocardiograms >=4 months apart (mean 2.9 +/- 2.1 years), evaluated in a
      nonreferral echocardiographic laboratory. The severity of AS was graded by the
      peak aortic velocity (Vmax) and progression was classified as slow or fast
      according to a cutoff value of 0.3 m/s increase annually. The end points were all
      cause mortality and a composite of all-cause mortality and aortic valve
      replacement (AVR). At baseline, 135 patients (88%) had mild-to-moderate and 18
      (12%) severe AS. Of the 153 patients, 49 (32%) showed fast progression (0.61 +/-
      0.32 m/s/yr) and 104 (68%) had slow progression (0.10 +/- 0.16 m/s/yr). Among the
      144 patients (94%) with clinical follow-up data, 40 died and 48 underwent AVR.
      The mortality rate was greater than that of the general population (p <0.001). On
      multivariate analysis, the independent predictors of mortality were the yearly
      change in Vmax (hazard ratio [HR] 13.352 per m/s increase, 95% confidence
      interval [CI] 5.136 to 34.713, p <0.001) and age (HR 1.122 per year, 95% CI
      1.0728 to 1.735, p <0.001). The predictors of the composite end point of death
      and AVR were the yearly change in Vmax (HR 12.307, 95% CI 6.024 to 25.140, p
      <0.001) and Vmax on the initial echocardiogram (HR 2.684, 95% CI 1.921 to 3.750,
      p <0.001). In conclusion, primary care patients with asymptomatic AS are usually
      elderly and frequently develop rapid hemodynamic progression, which independently
      predicts, not only AVR, but also overall mortality.

PMID- 22154323
TI  - Ursodeoxycholic acid improves insulin sensitivity and hepatic steatosis by
      inducing the excretion of hepatic lipids in high-fat diet-fed KK-Ay mice.
AB  - Type 2 diabetes mellitus is frequently accompanied by fatty liver/nonalcoholic
      fatty liver disease. Hence, accumulation of lipids in the liver is considered to
      be one of the risk factors for insulin resistance and metabolic syndrome.
      Ursodeoxycholic acid (UDCA) is widely used for the treatment of liver
      dysfunction. We investigated the therapeutic effects of UDCA on type 2 diabetes
      mellitus exacerbating hepatic steatosis and the underlying mechanisms of its
      action using KK-A(y) mice fed a high-fat diet. KK-A(y) mice were prefed a high
      fat diet; and 50, 150, and 450 mg/kg of UDCA was orally administered for 2 or 3
      weeks. Administration of UDCA decreased fasting hyperglycemia and
      hyperinsulinemia. Hyperinsulinemic-euglycemic clamp analyses showed that UDCA
      improved hepatic (but not peripheral) insulin resistance. Hepatic triglyceride
      and cholesterol contents were significantly reduced by treatment with UDCA,
      although the genes involved in the synthesis of fatty acids and cholesterol,
      including fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-coenzyme A
      reductase, were upregulated. Fecal levels of bile acids, neutral sterols, fatty
      acids, and phospholipids were significantly increased by UDCA treatment. The gene
      expression levels and protein phosphorylation levels of endoplasmic reticulum
      stress markers were not changed by UDCA treatment. These results indicate that
      UDCA ameliorates hyperglycemia and hyperinsulinemia by improving hepatic insulin
      resistance and steatosis in high-fat diet-fed KK-A(y) mice. Reduction of hepatic
      lipids might be due to their excretion in feces, followed by enhanced utilization
      of glucose for the synthesis of fatty acids and cholesterol. Ursodeoxycholic acid
      should be effective for the treatment of type 2 diabetes mellitus accompanying
      hepatic steatosis.

PMID- 22154324
TI  - Insulin resistance occurs in parallel with sensory neuropathy in streptozotocin
      induced diabetes in rats: differential response to early vs late insulin
      supplementation.
AB  - We investigated whether progressive sensory neuropathy was accompanied by changes
      in whole-body insulin sensitivity (WBIS) in rats made diabetic by streptozotocin
      (STZ). The effects of early and late insulin supplementation were also studied.
      The STZ-treated rats failed to gain weight and exhibited stable hyperglycemia and
      low plasma insulin levels with a decrease in nerve conduction velocity (NCV)
      measured in A and C fibers of the saphenous nerve. A decreased sensory
      neuropeptide (SNP) release such as that of substance P, somatostatin, and
      calcitonin gene-related peptide determined from organ fluid of tracheal
      preparations subjected to electrical field stimulation also occurred in diabetic
      animals. These features were accompanied by a decrease in WBIS measured by
      hyperinsulinemic-euglycemic glucose clamping and a decrease in insulin-stimulated
      glucose uptake in cardiac and gastrocnemius muscle. When insulin supplementation
      with slow-release implants (2 IU/d) was started 4 weeks after STZ injection,
      blood glucose level normalized. Both insulin sensitivity and sensory nerve
      function reflected in either NCV or SNP release completely recovered by the 12th
      post-STZ week. When the insulin implants were applied from the eighth post-STZ
      week, both WBIS and glucose uptake remained significantly decreased, with a
      seriously impaired NCV and SNP release with strong hyperglycemia. Late insulin
      supplementation, however, even by using double implantation from the 10th post
      STZ week, was unable to restore blood glucose, WBIS, NCV, and SNP release by the
      12th week. Insulin resistance occurs in parallel with sensory neuropathy in STZ
      diabetic rats. Both can be improved by early but not late insulin
      supplementation.

PMID- 22154325
TI  - Visceral fat accumulation is an indicator of adipose tissue macrophage
      infiltration in women.
AB  - We tested the hypothesis that visceral obesity is the best correlate of abdominal
      adipose tissue macrophage infiltration in women. Omental and subcutaneous fat
      samples were surgically obtained from 40 women (age, 47.0 +/- 4.0 years; body
      mass index, 28.4 +/- 5.8 kg/m(2)). CD68+ cells were identified using fluorescence
      immunohistochemistry. Expression of macrophage markers was measured by real-time
      reverse transcriptase polymerase chain reaction. Body composition and fat
      distribution were measured by dual-energy x-ray absorptiometry and computed
      tomography, respectively. Mean CD68+ cell percentage tended to be higher in
      subcutaneous (18.3%) compared with omental adipose tissue (15.5%, P = .07).
      Positive correlations were observed between CD68+ cell percentage as well as CD68
      messenger RNA expression in a given depot vs the other (P <= .01). Visceral
      adipose tissue area and omental adipocyte diameter were positively related to
      CD68+ cell percentage in omental fat (r = 0.52 and r = 0.35, P <= .05). Total and
      visceral adipose tissue areas as well as subcutaneous adipocyte diameter were
      significantly correlated with CD68+ cell percentage in subcutaneous adipose
      tissue (0.32 <= r <= 0.40, P <= .05). Adipose tissue areas and subcutaneous
      adipocyte diameter were also significantly associated with expression of commonly
      used macrophage markers including CD68 in the subcutaneous fat compartment (0.32
      <= r <= 0.57, P <= .05). Visceral adipose tissue area was the best correlate of
      CD68+ cell percentage in both omental and subcutaneous fat tissues, explaining,
      respectively, 20% and 12% of the variance in models also including subcutaneous
      adipose tissue area, adipocyte sizes, and total body fat mass. Visceral adipose
      tissue accumulation is the best correlate of macrophage infiltration in both the
      subcutaneous and omental fat compartments of lean to obese women.

PMID- 22154326
TI  - Dual pathways of p53 mediated glucolipotoxicity-induced apoptosis of rat
      cardiomyoblast cell: activation of p53 proapoptosis and inhibition of Nrf2-NQO1
      antiapoptosis.
AB  - Reactive oxygen species (ROS), driven by excessive levels of glucose and free
      fatty acids, appears to induce cell apoptosis. However, the underlying molecular
      mechanism of this process remains unclear in cardiac myocytes. We investigated
      the glucolipotoxicity effects of high glucose and palmitic acid (C16:0) on the
      rat cardiomyoblast cell line (H9c2) focusing on tumor suppressor p53. Cultured
      H9c2 rat cardiomyoblasts were exposed to palmitate and /or to an elevated glucose
      concentration for 18 hours. Only the glucolipotoxic condition of 30 mM glucose in
      combination with 250 MUM palmitate resulted in significant generation of ROS and
      upregulation of p53 which caused to an increased cleavage of caspase-3. On the
      other hand, the expression of NF-E2-related factor 2 (Nrf2) showed increased
      tendency while the expression of NAD(P)H: quinone oxidoreductase-1 (NQO1) was
      decreased. N-acetyl L cysteins and pifithrin-alpha, an inhibitor of p53 abrogated
      glucolipotoxicity-induced ROS generation and p53 expression. Chromatin
      immunoprecipitation analysis revealed that p53 interacted antioxidant responsive
      elements (ARE)-containing promoter of NQO1. Upregulated p53 counteracted the Nrf2
      induced transcription of ARE-containing promoter of NQO1 gene and leaded to
      decrease in NQO1 expression. We demonstrated that the elevated p53 mediated
      glucolipotoxicity-induced apoptosis of rat cardiomyoblast cell through dual
      pathways: stimulating pro-apoptosis signaling as well as suppressing anti
      apoptosis pathway of Nrf2-NQO1 signaling.

PMID- 22154327
TI  - Kidney disease in people with diabetes: the expanding epidemic.

PMID- 22154328
TI  - Prevalence of inadequate platelet inhibition by clopidogrel in patients receiving
      hemodialysis.

PMID- 22154329
TI  - Isolation of UmRrm75, a gene involved in dimorphism and virulence of Ustilago
      maydis.
AB  - Ustilago maydis displays dimorphic growth, alternating between a saprophytic
      haploid yeast form and a filamentous dikaryon, generated by mating of haploid
      cells and which is an obligate parasite. Induction of the dimorphic transition of
      haploid strains in vitro by change in ambient pH has been used to understand the
      mechanisms governing this differentiation process. In this study we used
      suppression subtractive hybridization to generate a cDNA library of U. maydis
      genes up-regulated in the filamentous form induced in vitro at acid pH.
      Expression analysis using quantitative RT-PCR showed that the induction of two
      unigenes identified in this library coincided with the establishment of
      filamentous growth in the acid pH medium. This expression pattern suggested that
      they were specifically associated to hyphal development rather than merely acid
      pH-induced genes. One of these genes, UmRrm75, encodes a protein containing three
      RNA recognition motifs and glycine-rich repeats and was selected for further
      study. The UmRrm75 gene contains 4 introns, and produces a splicing variant by a
      3'-alternative splicing site within the third exon. Mutants deleted for UmRrm75
      showed a slower growth rate than wild type strains in liquid and solid media, and
      their colonies showed a donut-like morphology on solid medium. Interestingly,
      although DeltaUmRrm75 strains were not affected in filamentous growth induced by
      acid pH and oleic acid, they exhibited reduced mating, post-mating filamentous
      growth and virulence. Our data suggest that UmRrm75 is probably involved in cell
      growth, morphogenesis, and pathogenicity in U. maydis.

PMID- 22154330
TI  - The antinociceptive activity of intrathecally administered amiloride and its
      interactions with morphine and clonidine in rats.
AB  - In this study, we aimed to evaluate the antinociceptive interaction between
      intrathecally administered amiloride and morphine or clonidine. Using rats
      chronically implanted with lumbar intrathecal catheters, we examined the ability
      of intrathecal amiloride, morphine, clonidine, and mixtures of amiloride-morphine
      and amiloride-clonidine to alter tail-flick latency. To characterize any
      interactions, isobolographic analysis was performed. The effects of pretreatment
      with intrathecally administered naloxone or yohimbine were tested. Intrathecal
      administration of amiloride (25-150 MUg), morphine (.25-10 MUg), or clonidine (.5
      10 MUg) alone produced significant dose-dependent antinociception in the tail
      flick test. The median effective dose (ED(50)) values for intrathecally
      administered amiloride, morphine, and clonidine were 120.5 MUg, 5.0 MUg, and 4.4
      MUg, respectively. Isobolographic analysis exhibited a synergistic interaction
      after coadministration of amiloride-morphine and amiloride-clonidine. Intrathecal
      pretreatment with naloxone (10 MUg) completely blocked the antinociceptive
      effects of morphine and the amiloride-morphine mixture. Intrathecal pretreatment
      with yohimbine (20 MUg) completely blocked the antinociceptive effect of
      clonidine and antagonized the effect of the amiloride-clonidine mixture. There
      was no motor dysfunction or significant change in blood pressure or heart rate
      after the intrathecal administration of amiloride, amiloride-morphine, and
      amiloride-clonidine. The synergistic effect observed after the coadministration
      of amiloride and morphine or clonidine suggests a functional interaction among
      calcium channels, MU-receptors and alpha(2)-receptors at the spinal cord level of
      the nociceptive processing system. PERSPECTIVE: Although intrathecal morphine and
      clonidine produces pronounced analgesia, antinociceptive doses of intrathecal
      morphine and clonidine produce several side effects, including hypotension,
      bradycardia, sedation, and tolerance. This article presents antinociceptive
      synergistic interaction between amiloride and morphine, amiloride, and clonidine
      on thermal nociceptive tests in the rat.

PMID- 22154331
TI  - Re: Noppers et al., Drug-induced liver injury following a reported course of
      ketamine treatment for chronic pain in CRPS type I patients. A report on 3 cases.
      Pain 2011;152:2173-8.

PMID- 22154333
TI  - Differential effects of experimental central sensitization on the time-course and
      magnitude of offset analgesia.
AB  - Pain perception is temporally altered during states of chronic pain and acute
      central sensitization; however, the mechanisms contributing to temporal
      processing of nociceptive information remain poorly understood. Offset analgesia
      is a phenomenon that reflects the presence of temporal contrast mechanisms for
      nociceptive information and can provide an end point to study temporal aspects of
      pain processing. In order to investigate whether offset analgesia is disrupted
      during sensitized states, 23 healthy volunteers provided real-time continuous
      visual analogue scale responses to noxious heat stimuli that evoke offset
      analgesia. Responses to these stimuli were evaluated during capsaicin-heat
      sensitization (45 degrees C stimulus, capsaicin cream 0.1%) and heat-only
      sensitization (40 degrees C stimulus, placebo cream). Capsaicin-heat
      sensitization produced significantly larger regions of secondary mechanical
      allodynia compared to heat-only sensitization. Although areas of mechanical
      allodynia were positively related to individual differences in heat pain
      sensitivity, this relationship was altered at later time points after capsaicin
      heat sensitization. Heat hyperalgesia was observed in the secondary region
      following both capsaicin-heat and heat-only sensitization. Increased latencies to
      maximal offset analgesia and prolonged aftersensations were observed only in the
      primary regions directly treated by capsaicin-heat or heat alone. However,
      contrary to the hypothesis that offset analgesia would be reduced following
      capsaicin-heat sensitization, the magnitude of offset analgesia remained
      remarkably intact after both capsaicin-heat and heat-only sensitization in zones
      of both primary and secondary mechanical allodynia. These data indicate that
      offset analgesia is a robust phenomenon and engages mechanisms that interact
      minimally with those supporting acute central sensitization.

PMID- 22154334
TI  - Clinical utility and prognostic value of galactomannan in neutropenic patients
      with invasive aspergillosis.
AB  - Invasive aspergillosis (IA) is a major cause of morbidity and mortality in
      profoundly neutropenic patients. Delayed diagnosis and therapy may lead to poor
      outcomes. AIMS: The objective of this study was to assess the performance
      characteristics of the galactomannan (GM) assay in serum and bronchoalveolar
      lavage specimens for the diagnosis of IA in neutropenic patients with
      hematological malignancies. We also evaluated the prognostic outcome. PATIENTS
      AND METHODS: A total of 1198 serum samples and 42 BAL from 235 neutropenic
      patients were tested with a GM elisa platelia test. We used Cox modeling of time
      to 6- and 12-week mortality for GM level at the time of diagnosis (GM0) and GM
      decay in the week following diagnosis in proven and probable IA patients with
      more than two GM values. RESULTS: There were three proven, 55 probable, and four
      possible cases of IA. The sensitivity and specificity of the GM test were 96.8%
      and 82.4% respectively. In BAL samples, sensitivity was 86% and the specificity
      93%. BAL GM was more sensitive than microscopy (22.2%) and BAL culture (38.9%).
      Among patients with proven/probable IA, serum and BAL GM were in agreement for
      92.8% of paired samples. The hazard ratio (HR) of GM0 and 1-week GM decay per
      unit increase in Aspergillus enzyme immunoassay (EIA) was 1.044 (95% CI, 0.738 to
      1.476) and 0.709 (95% CI, 0.236 to 2.130) respectively. CONCLUSION: We found good
      correlation between the GM0 and GM decay combination and outcome of IA patients.
      The GM is a useful tool for diagnosis and monitoring of IA.

PMID- 22154332
TI  - Sex similarities and differences in pain-related periaqueductal gray
      connectivity.
AB  - This study investigated sex similarities and differences in pain-related
      functional connectivity in 60 healthy subjects. We used functional magnetic
      resonance imaging and psychophysiological interaction analysis to investigate how
      exposure to low vs high experimental pain modulates the functional connectivity
      of the periaqueductal gray (PAG). We found no sex differences in pain thresholds,
      and in both men and women, the PAG was more functionally connected with the
      somatosensory cortex, the supplemental motor area, cerebellum, and thalamus
      during high pain, consistent with anatomic predictions. Twenty-six men displayed
      a pain-induced increase in PAG functional connectivity with the amygdala caudate
      and putamen that was not observed in women. In an extensive literature search, we
      found that female animals have been largely overlooked when the connections
      between the PAG and the amygdala have been described, and that women are
      systematically understudied with regard to endogenous pain inhibition. Our
      results emphasize the importance of including both male and female subjects when
      studying basic mechanisms of pain processing, and point toward a possible sex
      difference in endogenous pain inhibition.

PMID- 22154335
TI  - Asymptomatic carriage of Leishmania in family members of patients with visceral
      leishmaniasis in Central Tunisia.
AB  - INTRODUCTION: In Tunisia, asymptomatic carriage of Leishmania is poorly
      documented. OBJECTIVE: The aim of the present study was to estimate the frequency
      of asymptomatic infection among the family members of patients with patent
      visceral leishmaniasis by using the Western blotting kit based on 14 and 16kDa
      bands. MATERIAL AND METHODS: We tested 94 sera collected from 24 patients with
      patent visceral leishmaniasis and 70 from their families' members. RESULTS: The
      rate of seropositivity was 100% in the group of patients and 54.3% in the group
      of families' members. The analysis of the Western blotting patterns showed that
      the 33kDa, 24kDa and to a lesser extent the 22kDa band were very indicative of
      patent visceral leishmaniasis in contrast to asymptomatic infection where these
      bands were very rarely detected. CONCLUSION: The results reported herein showed
      the high frequency of asymptomatic carriers of Leishmania among the families'
      members of visceral leishmaniasis cases and the usefulness of the Western
      blotting as a screening technique and in distinguishing between patent visceral
      leishmaniasis and the asymptomatic carriage of Leishmania.

PMID- 22154336
TI  - Multicentric epithelioid hemangioendothelioma of bone. Report of a case with
      radiologic-pathologic correlation.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of uncertain
      biologic behavior. Most cases come out as a single lesion of the soft tissue but
      also may appear in the lung, liver, and other locations. Epithelioid
      hemangioendothelioma of bone is an extremely rare tumor and more prevalent in the
      second and third decades of life; its behavior is uncertain, it most commonly is
      unifocal, and it affects preferentially lower extremities. In this work, we
      present the clinical, radiologic, and pathologic findings of a 19-year-old man
      with a multicentric EHE of bone that involved 3 vertebrae and developed lung
      metastasis.

PMID- 22154337
TI  - Spindle epithelial tumor with thymus-like differentiation of the thyroid
      (SETTLE): Report of two cases (one associated with a parathyroid adenoma).
AB  - Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare
      tumor usually localized in the thyroid gland and perithyroid tissues. It is
      considered to arise from ectopic thymic tissue or branchial pouch remnants. It
      occurs more frequently in children and adolescents. We report 2 cases of spindle
      epithelial tumor with thymus-like differentiation localized in the thyroid gland,
      and 1 of them was associated with a parathyroid adenoma. We emphasize the need
      for a close and long-term follow-up in these patients.

PMID- 22154338
TI  - Gender, gender roles, and anxiety: perceived confirmability of self report,
      behavioral avoidance, and physiological reactivity.
AB  - Despite the well-documented gender effect in anxiety, less is known about
      contributing factors to women's greater risk for anxiety and fears. The present
      study examined the relationship between gender, gender role orientation (i.e.,
      expressivity/instrumentality) and fear of harmless insects (tarantula), using a
      multimodal approach of self-report measures, a Behavioral Approach Test (BAT),
      and physiological reactivity. Participants (144 college students; 67 women, 77
      men) completed a questionnaire packet and then were instructed to approach a
      tarantula. We were unable to replicate Pierce and Kirkpatrick's (1992) findings
      that men underreport anxiety. Consistent with the literature, women in the study
      experienced greater anxiety and avoidance compared to men. However, men and women
      did not differ on physiological reactivity during the first 2 min of the BAT. The
      concordance across avoidance, anxiety and heart rate reactivity differed by
      gender, suggesting that men and women have different experiences when faced with
      a fearful object. Furthermore, instrumentality (masculinity) was negatively
      related to anticipatory anxiety for women but not for men.

PMID- 22154339
TI  - Organotins in North Sea brown shrimp (Crangon crangon L.) after implementation of
      the TBT ban.
AB  - The organotin (OT) compounds tributyltin (TBT) and triphenyltin (TPhT) are potent
      biocides that have been used ubiquitously in antifouling paints and pesticides
      since the mid-1970s. These biocides are extremely toxic to marine life,
      particularly marine gastropod populations. The European Union therefore took
      measures to reduce the use of TBT-based antifouling paints on ships and
      ultimately banned these paints in 2003. Despite sufficient data on OT
      concentrations in marine gastropods, data are scarce for other species such as
      the North Sea brown shrimp (Crangon crangon), a dominant crustacean species in
      North Sea inshore benthic communities. The present study provides the first
      spatial overview of OT concentrations in North Sea brown shrimp. We have compared
      these data with historical concentrations in shrimp as well as with sediment
      concentrations. We have also addressed the effect on the shrimp stock and any
      human health risks associated with the OT concentrations found. TBT and TPhT in
      shrimp tail muscle ranged from 4 to 124 and from 1 to 24 MUg kg(-1) DW,
      respectively. High levels are accumulated in estuarine areas and are clearly
      related with sediment concentrations (biota-sediment accumulation factor ~10).
      Levels have decreased approximately 10-fold since the ban took effect, coinciding
      with a recovery of the shrimp stock after 30 years of gradual regression.
      Furthermore, the OT levels found in brown shrimp no longer present a human health
      risk.

PMID- 22154340
TI  - Nitrate reduction by green rusts modified with trace metals.
AB  - A kinetic study of nitrate reduction by green rust (GR), a group of layered
      Fe(II)-Fe(III) hydroxide solids, was performed using a batch reactor system. The
      reduction rate of nitrate by GRs was affected by the anion content in the
      interlayer of GRs. GR containing F(-) (GR-F) showed the fastest reduction rate
      while GR-SO(4) showed 9 times slower reaction rate than GR-F. The addition of 1mM
      Pt or Cu to GR that contained 85 mM Fe(II) improved the reduction kinetics of
      nitrate by up to 200 times. Pt was an effective activating agent for all GRs. The
      sequential step reaction model that we proposed appropriately simulated the
      experimental data. The fastest nitrate reduction by GR-F with Pt was achieved at
      pH 9 among 7.5 to 11. At that condition, 1mM nitrate transformed completely into
      ammonium within 23 min.

PMID- 22154341
TI  - VOC composition of current motor vehicle fuels and vapors, and collinearity
      analyses for receptor modeling.
AB  - The formulation of motor vehicle fuels can alter the magnitude and composition of
      evaporative and exhaust emissions occurring throughout the fuel cycle.
      Information regarding the volatile organic compound (VOC) composition of motor
      fuels other than gasoline is scarce, especially for bioethanol and biodiesel
      blends. This study examines the liquid and vapor (headspace) composition of four
      contemporary and commercially available fuels: gasoline (<10% ethanol), E85 (85%
      ethanol and 15% gasoline), ultra-low sulfur diesel (ULSD), and B20 (20% soy
      biodiesel and 80% ULSD). The composition of gasoline and E85 in both neat fuel
      and headspace vapor was dominated by aromatics and n-heptane. Despite its low
      gasoline content, E85 vapor contained higher concentrations of several VOCs than
      those in gasoline vapor, likely due to adjustments in its formulation.
      Temperature changes produced greater changes in the partial pressures of 17 VOCs
      in E85 than in gasoline, and large shifts in the VOC composition. B20 and ULSD
      were dominated by C(9) to C(16)n-alkanes and low levels of the aromatics, and the
      two fuels had similar headspace vapor composition and concentrations. While the
      headspace composition predicted using vapor-liquid equilibrium theory was closely
      correlated to measurements, E85 vapor concentrations were underpredicted. Based
      on variance decomposition analyses, gasoline and diesel fuels and their vapors
      VOC were distinct, but B20 and ULSD fuels and vapors were highly collinear. These
      results can be used to estimate fuel related emissions and exposures,
      particularly in receptor models that apportion emission sources, and the
      collinearity analysis suggests that gasoline- and diesel-related emissions can be
      distinguished.

PMID- 22154344
TI  - [Inequity in the use of health and social care services for disabled individuals
      in Spain].
AB  - OBJECTIVES: The objective of "equal access for equal need" is part of the policy
      agenda of most European countries. Several studies have provided evidence of
      equity in the use of healthcare services by the adult population in Spain.
      However, less attention has been paid to equity in access to health and social
      care services among the disabled population. In this study, we present an
      analysis of the distribution of unmet need for a set of economic, health and
      social care services by the disabled population in Spain. METHODS: Horizontal
      inequity in unmet need for various socioeconomic services was measured by using
      data from the EDAD2008 survey conducted in the disabled population in Spain and
      methods based on the Concentration Index. RESULTS: In Spain the distribution of
      unmet need among disabled individuals is not equitable. The greatest proportion
      of unmet needs is concentrated among individuals at the bottom of the income
      distribution. In addition, the level of horizontal inequity differs depending on
      the individual's gender and age, together with the specific service analyzed and
      the reasons giving rise to this unmet need. CONCLUSIONS: Socioeconomic status is
      important in access to health and social care services by the disabled. These
      results will allow policymakers to design policies aimed at reducing barriers to
      health and social care services among the disabled population in Spain.

PMID- 22154342
TI  - Detection of human erythrocytes influenced by iron deficiency anemia and
      thalassemia using atomic force microscopy.
AB  - PURPOSE: Iron deficiency anemia (IDA) and thalassemia (THAL) are two types of
      microcytic anemia, and both of these conditions disturb the morphology and
      function of erythrocytes at the molecular level. The ability to distinguish
      between thalassemic and iron deficiency anemia microcytosis has important
      clinical implications. The purpose of this study was to show that
      pathophysiological changes to erythrocytes could be detected at the nanometer
      scale, which is important for the early diagnosis of anemia and for
      distinguishing between IDA and THAL. METHODS: Blood samples were taken from six
      healthy volunteers and six patients with either iron deficiency anemia or
      thalassemia. Changes in the morphological of erythrocytes were studied at the
      nanometer level using atomic force microscopy (AFM). RESULTS: There were dramatic
      overall shape and surface membrane deformations of the erythrocytes associated
      with iron deficiency anemia and thalassemia compared to healthy erythrocytes.
      Healthy and pathological erythrocytes of iron deficiency anemia and thalassemia
      could be distinguished by the morphologic parameters of width, length, the ratio
      of length to width, valley, peak, valley-to-peak, standard deviations, and
      surface fluctuation. These AFM parameters of erythrocyte morphology differed
      greatly between iron deficiency anemia and thalassemia. CONCLUSION: AFM was found
      to be an extremely useful tool for detecting and distinguishing between iron
      deficiency anemia and thalassemia. Erythrocyte morphology is an important
      determinant for diagnosing and distinguishing IDA and THAL.

PMID- 22154345
TI  - [Influence of income, income inequalities and social capital on the health of
      persons aged 65 and over in Spain in 2007].
AB  - The aim of this study is to evaluate the influence of personal income [absolute
      income hypothesis (AIH)], income inequality and welfare [relative income
      hypothesis (RIH)], and social capital on the health of older people. Multi-level,
      cross-sectional logit models are calculated separately for women and men. The
      database employed was the Spanish Life Conditions Survey for 2007. The population
      consists of 6,259 persons aged over 65 years living in the 17 autonomous regions
      of Spain. The results confirm the AIH hypothesis: higher personal income is
      associated with better health. Education is also associated with better self
      perceived health. The RIH hypothesis is partially confirmed due to the
      association between the Gini coefficient, regional per capita welfare and self
      perceived health in older people, but only for women. Two different measures of
      social capital are used: the value of services of social capital and the
      percentage of people aged over 65 belonging to an association. Both factors are
      statistically associated with better self-perceived health in women. This study
      is the first to contrast the associations among income, income inequalities,
      social capital and the health of elders in Spain.

PMID- 22154346
TI  - [Estimation of the number of individuals entitled to dependency benefits and of
      the associated cost of care in Spain for 2007-2045].
AB  - OBJECTIVE: To provide estimates of the number of dependent individuals per grade
      and level for the period 2007-2045 and the cost associated with the care of these
      individuals for the System for Promoting the Autonomy and Care of Dependent
      Persons [Sistema para la Autonomia y Atencion a la Dependencia (SAAD)]. METHODS:
      Based on the Disabilities, Independence and Dependency Situations Survey (2008)
      and the scale for the assessment of grades and levels of dependency, we applied a
      two-stage estimation procedure to project the number of dependent individuals. In
      the first stage, we calculated the probability of a person being dependent and
      entitled to benefits by using a logit model. In the second stage, using an
      ordered logit model, we calculated the probability of distinct grades and levels
      of dependency in dependent persons entitled to benefits. Subsequently, we
      calculated expenditure projections based on average cost per point scale by grade
      and level of dependency. RESULTS: Our results suggest a higher incidence of
      situations of dependency in female beneficiaries than in male beneficiaries, with
      higher growth rates for almost all categories of grade and level between 2007 and
      2045. We estimated that in 2045 there will be 1,592,798 beneficiaries of the SAAD
      (596,332 men and 996,466 women). Moreover, between 2007 and 2045 the cost of care
      for dependent people will be multiplied by 2.64 for male beneficiaries and by
      2.89 for female beneficiaries, amounting to 41,926 million euros in 2045.
      CONCLUSIONS: The care of dependent persons is a major challenge for Spanish
      society both because of the number of persons that will require care and because
      of the greater economic cost involved. These findings should prompt a debate on
      how to fund services and benefits and how to ensure the sustainability of the
      system.

PMID- 22154347
TI  - The role of volleyball expertise in motor simulation.
AB  - We explored the impact of motor experience on the interaction between implicit
      motor simulation and language-processing. In an action familiarity judgment task,
      expert volleyball players, fans and novices were presented with semantically
      correct sentences describing possible and not possible motor actions, all as
      negative or positive contexts, e.g., "Don't shank!" or "Assist!". As processing
      negated action-phrases is known to reduce simulation states, exposure to negative
      or positive contexts was used here to test how simulation varies according to
      motor feasibility (possible, impossible) and experience (experts and fans). A
      significant group*stimulus*context interaction showed that athletes and fans,
      took longer to process negative than positive contexts for possible actions,
      compared to action-impossible sentences. In addition, experts were significantly
      faster and more accurate than fans and, in turn, they were both more accurate
      than novices. Thus, implicit motor simulation impacts on action-verb processing
      depending on (i) the domain-relevant expertise, (ii) the feasibility of the
      actions, and (iii) on whether scenes are presented in a negated context. These
      results suggest that the implicit triggering of motor representations is
      modulated by the context and it is tuned to people's motor repertoire, even when
      actions are described linguistically.

PMID- 22154348
TI  - A load on my mind: evidence that anhedonic depression is like multi-tasking.
AB  - Multi-tasking can increase susceptibility to distraction, affecting whether
      irrelevant objects capture attention. Similarly, people with depression often
      struggle to concentrate when performing cognitively demanding tasks. This
      parallel suggests that depression is like multi-tasking. To test this idea, we
      examined relations between self-reported levels of anhedonic depression (a
      dimension that reflects the unique aspects of depression not shared with anxiety
      or other forms of distress) and attention capture by salient items in a visual
      search task. Furthermore, we compared these relations to the effects of
      performing a concurrent auditory task on attention capture. Strikingly, both
      multi-tasking and elevated levels of anhedonic depression were associated with
      increased capture by uniquely colored items, but decreased capture by abruptly
      appearing items. At least with respect to attention capture and distraction,
      depression seems to be functionally comparable to juggling a second, unrelated
      cognitive task.

PMID- 22154349
TI  - 5-(2-amino-pyrimidin-4-yl)-1H-pyrrole and 2-(2-amino-pyrimidin-4-yl)-1,5,6,7
      tetrahydro-pyrrolo[3,2-c]pyridin-4-one derivatives as new classes of selective
      and orally available Polo-like kinase 1 inhibitors.
AB  - The discovery and characterization of two new chemical classes of potent and
      selective Polo-like kinase 1 (PLK1) inhibitors is reported. For the most
      interesting compounds, we discuss the biological activities, crystal structures
      and preliminary pharmacokinetic parameters. The more advanced compounds inhibit
      PLK1 in the enzymatic assay at the nM level and exhibit good activity in cell
      proliferation on A2780 cells. Furthermore, these compounds showed high levels of
      selectivity on a panel of unrelated kinases, as well as against PLK2 and PLK3
      isoforms. Additionally, the compounds show acceptable oral bioavailability in
      mice making these inhibitors suitable candidates for further in vivo activity
      studies.

PMID- 22154350
TI  - Discovery of bacterial NAD+-dependent DNA ligase inhibitors: improvements in
      clearance of adenosine series.
AB  - Optimization of clearance of adenosine inhibitors of bacterial NAD(+)-dependent
      DNA ligase is discussed. To reduce Cytochrome P-450-mediated metabolic clearance,
      many strategies were explored; however, most modifications resulted in compounds
      with reduced antibacterial activity and/or unchanged total clearance. The alkyl
      side chains of the 2-cycloalkoxyadenosines were fluorinated, and compounds with
      moderate antibacterial activity and favorable pharmacokinetic properties in rat
      and dog were identified.

PMID- 22154351
TI  - Synthesis and biological evaluation of substituted pyrazoles as blockers of
      divalent metal transporter 1 (DMT1).
AB  - Three distinct series of substituted pyrazole blockers of divalent metal
      transporter 1 (DMT1) were elaborated from the high-throughput screening
      pyrazolone hit 1. Preliminary hit-to-lead efforts revealed a preference for
      electron-withdrawing substituents in the 4-amido-5-hydroxypyrazole series 6a-l.
      In turn, this preference was more pronounced in a series of 4-aryl-5
      hydroxypyrazoles 8a-j. The representative analogs 6f and 12f were found to be
      efficacious in a rodent model of acute iron hyperabsorption. These three series
      represent promising starting points for lead optimization efforts aimed at the
      discovery of DMT1 blockers as iron overload therapeutics.

PMID- 22154352
TI  - A neurocomputational approach to obsessive-compulsive disorder.
AB  - A recent article shows that a change in a single parameter in a neural-network
      model of brain dynamics leads to repetitive behaviors that resist termination and
      towards which the network tends. These findings may have implications for
      obsessive-compulsive disorder and are consistent with evidence of glutamatergic
      hyperactivity in this disorder.

PMID- 22154353
TI  - Statistical properties of support vector machines with forgetting factor.
AB  - Introducing a forgetting factor allows a support vector machine to solve time
      varying problems adaptively. However, the exponential forgetting factor proposed
      in an earlier work does not ensure convergence of average generalization error
      even for a simple linearly separable problem. To guarantee convergence, we
      propose a factorial forgetting factor which decays factorially over time. We
      approximately derive the average generalization error of the factorial forgetting
      factor as well as that of the exponential forgetting factor using a simple one
      dimensional problem, and confirm our theory by computer simulations. Finally, we
      show that our theory can be extended to arbitrary types of forgetting factors for
      simple linearly separable cases.

PMID- 22154354
TI  - Asynchronous frameless event-based optical flow.
AB  - This paper introduces a process to compute optical flow using an asynchronous
      event-based retina at high speed and low computational load. A new generation of
      artificial vision sensors has now started to rely on biologically inspired
      designs for light acquisition. Biological retinas, and their artificial
      counterparts, are totally asynchronous and data driven and rely on a paradigm of
      light acquisition radically different from most of the currently used frame
      grabber technologies. This paper introduces a framework for processing visual
      data using asynchronous event-based acquisition, providing a method for the
      evaluation of optical flow. The paper shows that current limitations of optical
      flow computation can be overcome by using event-based visual acquisition, where
      high data sparseness and high temporal resolution permit the computation of
      optical flow with micro-second accuracy and at very low computational cost.

PMID- 22154355
TI  - Statins as a possible cause of inflammatory and necrotizing myopathies.
AB  - BACKGROUND: Hydroxy-methyl-glutaryl Co-A reductase (HMGCR) inhibitors or statins
      are a well recognized cause of a variety of skeletal myopathic effects which
      generally resolve on stopping the medication. Recent reports, however, suggest
      that statins are associated with a unique autoimmune myopathy wherein symptoms
      persist or even progress after statin discontinuation and require
      immunosuppressive therapy. We performed a systematic review to examine the
      association of statins with inflammatory (dermatomyositis/polymyositis) and
      necrotizing myopathies. METHODS: We searched PubMed, Ovid and Scopus for English
      language articles addressing statin associated inflammatory and necrotizing
      myopathies. Given the paucity of cases, we extended the search to include
      articles in all languages. RESULTS: The search yielded 14 articles reporting a
      possible association of statins with inflammatory myopathies describing 10 cases
      of polymyositis and 14 cases of dermatomyositis, and 4 articles reporting a
      possible association of statins with necrotizing myopathies describing 63 cases.
      One study identified a unique antibody directed against HMGCR in patients with
      necrotizing myopathy. Systemic immunosuppressive therapy was required in majority
      of these cases for resolution of symptoms. CONCLUSION: Statins have recently been
      associated with a variety of inflammatory myopathies including polymyositis,
      dermatomyositis, and a necrotizing myopathy. The association of statins with
      necrotizing myopathy is strengthened by the discovery that the serum of some of
      these patients contains an anti-HMGCR antibody. This suggests that statins can
      cause or unmask an immune mediated myopathy.

PMID- 22154356
TI  - Recurrent hypersomnia due to occult hepatic encephalopathy.

PMID- 22154357
TI  - Association of genetic polymorphism of glutathione S-transferase (GSTM1, GSTT1,
      GSTP1) with bladder cancer susceptibility.
AB  - The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify
      carcinogenic compounds by conjugating glutathione to facilitate their removal.
      Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for
      bladder cancer. Studies focusing on GSTs gene variants relationship with the risk
      of bladder cancer have produced conflicting and inconsistent results. We examine
      the association between genetic polymorphism of glutathione S-transferase P1,
      GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC).
      The study population consisted of 166 histologically confirmed male bladder TCC
      cases and 332 healthy male controls. Genotyping was done using the polymerase
      chain reaction restriction fragment length polymorphism (PCR-RFLP) method and
      also investigated combined gene interactions. The GSTP1 Val/Val genotype was
      significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64-6.34),
      whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82-2.62; P
      = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79-1.67; P = 0.74) did not
      reach statistical significance. There was a significant multiple interaction
      between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for
      interaction = 0.02). The risk associated with the concurrent presence of GSTM1
      positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34-5.54) and GSTT1
      positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54-4.72) was
      statistically significant. Patients carrying GSTP1 Val/Val genotype were at
      increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73-19.25) and
      muscle invasive (OR = 10.67, 95% CI: 6.34-21.75) bladder cancer. High risk for
      bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val
      or Val/Val (OR = 4.76, 95% CI: 2.68-18.72) and GSTM1 null/GSTT1 null/GSTP1
      Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76-14.72) genotype variant. This study
      suggests that the GSTP1 polymorphism and its combination with GSTM1, and GSTT1
      may be associated with bladder cancer susceptibility in the Iranian population.
      Further confirmation in large population-based studies is needed.

PMID- 22154358
TI  - Stress-activated kinase pathway alteration is a frequent event in bladder cancer.
AB  - OBJECTIVES: The stress-activated MAP kinases (SAPK) signaling pathways play a
      critical role in the cellular response to toxins and physical stress, mediate
      inflammation, and modulate carcinogenesis and tumor metastasis. The stress
      activated MAP kinases (MAPK) c-Jun N-terminal kinase (JNK) and p38 are activated
      upon phosphorylation by a widely expressed and conserved family of upstream MAP
      kinase kinases (MAP2K). Signaling mediated by p38 and JNK has well-established
      importance in cancer, yet the contribution of this pathway in urothelial bladder
      cancer is not understood. This study evaluated stress-activated MAP kinase
      pathway expression in cell lines derived from human urothelial carcinomas.
      MATERIALS AND METHODS: Total protein lysates from a panel of human urothelial
      bladder cancer cell lines (RT4, T24, UMUC-3, J82, 5637, 253J, and 253J-BV) were
      analyzed by immunoblotting for the JNK and p38 MAPKs, as well as MKK3, MKK4,
      MKK6, and MKK7. Quantitative real time PCR was utilized to determine mRNA
      expression levels of the MAP2Ks. Stress stimuli (sorbitol, hydrogen peroxide, and
      UV irradiation) were used to active p38, which was measured by phospho-antibody.
      RESULTS: Although protein levels were variable, all cell lines expressed p38 and
      JNK. On the other hand, with the exception of the well-differentiated cell line
      RT4, each cell line had a reduction or absence of expression of one or more
      MAP2K. 253J and 253J-BV exhibited no expression of MKK6, even when an excess of
      protein was queried. mRNA levels indicated that both transcriptional and post
      transcriptional mechanisms are involved in the regulation of MAP2Ks. Decreased
      MAP2K expression correlated with decreased ability to activate p38 in response to
      stress stimuli. CONCLUSIONS: Aberrant MAP2K protein expression indicates that
      altered cellular signal transduction mediated via JNK and p38 may be common in
      bladder cancer. Down-regulation of MAP2Ks likely occurs at both the
      transcriptional and post-transcriptional levels. Consistent with the known
      function of p38 and JNK in apoptosis, defects in normal pathway function caused
      by decreased expression of upstream MAP2Ks may provide a survival advantage to
      bladder cancer cells. Further investigations should focus on identifying a
      functional role for these pathways in bladder cancer development.

PMID- 22154359
TI  - Gender differences in factors associated with alcohol drinking: delay discounting
      and perception of others' drinking.
AB  - BACKGROUND: Excessive alcohol consumption in college students is associated with
      impulsivity and with overestimating levels of others' drinking; however, females'
      and males' drinking may be differently impacted by their overestimations. We
      examined whether moderate drinkers discount alcohol rewards differently from
      money rewards and whether their estimate of others' drinking is more closely
      associated with own-drinking for males than females. METHOD: College students
      completed two delay discounting tasks in which they chose between money rewards
      and between alcohol rewards, varying in amount and delay to receipt. Participants
      also completed questionnaires about their own and others' drinking. RESULTS: Area
      under the curve (AUC) relating delay to subjective value was smaller for alcohol
      than money rewards, implying steeper discounting of alcohol rewards. Regression
      analyses showed that females' number of drinks per sitting was related only to
      AUC for money, while males' drinks per sitting was related to their estimates of
      others' drinks. CONCLUSION: The relationship between alcohol consumption and
      discounting was replicated. This study also indicated that social norms play a
      larger role in determining males' drinking than females'.

PMID- 22154360
TI  - Intravenous or oral vinorelbine plus capecitabine as first-line treatment in HER2
      metastatic breast cancer: joint analysis of 2 consecutive prospective phase II
      trials.
AB  - BACKGROUND: The purpose of this study was to assess the activity and safety of
      the combination of vinorelbine (VNR) and capecitabine (CAP) as first-line
      treatment in HER2-negative (HER(-)) metastatic breast cancer (MBC). PATIENTS AND
      METHODS: Patients (42) enrolled in trial A received intravenous (i.v.) VNR 25
      mg/m2 on days 1 and 8 of a 21-day cycle combined with CAP 1000 mg/m2 twice daily
      for 14 consecutive days followed by 1 week of rest. Trial B (46 patients)
      followed trial A when the oral formulation of VNR became available at our
      institution. Patients received oral VNR (60 mg/m(2) on days 1-8) combined with
      the same CAP schedule as in trial A. RESULTS: The response rate (RR) in trial A
      was 73.2% (95% confidence interval [CI], 56.4-82.8), including 12.2% complete
      responses (CRs). Clinical benefit was achieved in 78% of patients (95% CI, 63.2
      87.9). In trial B, overall RR was 76% (95% CI, 62.0-86.0), with 13% CRs and
      clinical benefit of 80.4% (95% CI, 66.8-89.3). In trial A, median progression
      free survival (PFS) was 8.2 months (range, 6-14+ months) and median overall
      survival (OS) was 32.4 months (range, 17-36+ months). In trial B, median PFS and
      OS were 8.8 months (range, 8-21+ months) and 34.3 months (14-39+ months),
      respectively. Treatment-related toxicity was manageable. Quality of life
      assessment showed a statistically significant difference regarding body image (p
      = .001), sexual functioning (p = .02), and future perspectives (p = .03) in women
      receiving chemotherapy fully by the oral route. CONCLUSION: This joint analysis
      shows that both tested schedules can produce high objective RRs with encouraging
      PFS, manageable toxicity profile, and suggested benefit on some aspects of
      quality of life for the fully oral combination.

PMID- 22154361
TI  - Increased heparanase level and procoagulant activity in orthopedic surgery
      patients receiving prophylactic dose of enoxaparin.
AB  - BACKGROUND: Orthopedic hip and knee surgeries are followed by a hypercoagulable
      state. Heparanase is implicated in inflammation, coagulation activation and
      angiogenesis. Recently, heparanase was shown to directly interact with tissue
      factor (TF) and to enhance the generation of factor Xa (Nadir et al.,
      Haematologica, 2010). In addition, an assay assessing heparanase procoagulant
      activity has been lately developed (Nadir et al., Thromb Res, 2011). In the
      present study heparanase level and procoagulant activity in patients undergoing
      orthopedic surgery were assessed. METHODS: The study group included 50 orthopedic
      patients. 31 patients underwent hip surgery and 19 had knee operation. 15
      individuals suffered from traumatic hip fractures and 35 had osteoarthrosis of
      hip or knee joints. All patients received prophylactic dose of enoxaparin
      starting 6-8 hours post operation and lasting for 5 weeks. Plasma samples were
      drawn preoperatively and at 1 hour, 1 week and 1 month post operation. Samples
      were tested for heparanase levels by ELISA and TF/heparanase complex activity, TF
      activity, heparanase procoagulant activity, factor Xa and thrombin levels using
      chromogenic substrates. RESULTS: Heparanase levels were significantly higher 1
      hour and 1 week post operatively compared to preoperative levels (p<0.05,
      p<0.005, respectively). The most dramatic changes were observed in heparanase
      procoagulant activity reaching a 2 fold increase 1 week postoperatively and 1.7
      fold increase 1month after surgery (p<0.0001, p<0.0001, respectively). Levels of
      factor Xa and thrombin did not significantly change. CONCLUSIONS: Heparanase is
      involved in coagulation activation of orthopedic surgery patients. Heparanase
      procoagulant activity is highest 1 week postoperatively and remains high 1month
      after operation. Considering extending prophylactic anticoagulant therapy or
      evaluating heparanase procoagulant activity may potentially prevent late
      thrombotic events.

PMID- 22154362
TI  - Androgen receptor expression is usually maintained in initial surgically resected
      breast cancer metastases but is often lost in end-stage metastases found at
      autopsy.
AB  - Androgen receptor (AR) is expressed in approximately 70% of primary breast
      carcinomas (PBCs) and is a promising therapeutic target for metastatic breast
      carcinoma (MBC). Here, we examine AR expression in a population of initial
      surgically resected metastases and a separate cohort of end-stage metastases
      harvested at autopsy compared with their matched PBCs. Tissue microarrays of
      matched PBC and MBC were labeled by immunohistochemistry for AR, estrogen
      receptor (ER), progesterone receptor (PR), and Her2 and classified into the
      following previously described categories: luminal (ER/PR+/Her2-), triple
      negative (ER/PR/Her2-), Her2 (ER/PR-/Her2+), and luminal loss (ER/PR loss from
      primary to metastasis). In the cohort of surgically resected metastases (n = 16),
      AR was expressed in 12 of 16 PBC and maintained in 11 of 12 corresponding MBCs.
      Of these, 36% showed stronger AR labeling in the metastases and none showed a
      decrease. In the cohort of metastases harvested at autopsy (n = 16), AR was
      expressed in 11 of 16 primary carcinomas and maintained in only 5 of 11
      corresponding metastases. Of these, none showed increased AR and 80% showed
      decreased AR labeling. AR expression is overwhelmingly concordant between matched
      PBC and MBC at initial presentation. These findings validate AR as a therapeutic
      target in MBC and suggest that AR may need to be reevaluated in metastases even
      if the primary is negative. However, similar to ER/PR, AR expression is often
      decreased with a trend toward complete loss in end-stage metastases, suggesting a
      shift of AR expression between initial and end-stage metastases. This suggests an
      opportunity for targeted antiandrogen therapy at an earlier stage of disease
      progression.

PMID- 22154364
TI  - Advances in top-down and bottom-up surface nanofabrication: techniques,
      applications & future prospects.
AB  - This review highlights the most significant advances of the nanofabrication
      techniques reported over the past decade with a particular focus on the
      approaches tailored towards the fabrication of functional nano-devices. The
      review is divided into two sections: top-down and bottom-up nanofabrication.
      Under the classification of top-down, special attention is given to technical
      reports that demonstrate multi-directional patterning capabilities less than or
      equal to 100 nm. These include recent advances in lithographic techniques, such
      as optical, electron beam, soft, nanoimprint, scanning probe, and block copolymer
      lithography. Bottom-up nanofabrication techniques--such as, atomic layer
      deposition, sol-gel nanofabrication, molecular self-assembly, vapor-phase
      deposition and DNA-scaffolding for nanoelectronics--are also discussed.
      Specifically, we describe advances in the fabrication of functional
      nanocomposites and graphene using chemical and physical vapor deposition. Our aim
      is to provide a comprehensive platform for prominent nanofabrication tools and
      techniques in order to facilitate the development of new or hybrid
      nanofabrication techniques leading to novel and efficient functional
      nanostructured devices.

PMID- 22154363
TI  - EGFR, HER2, survivin, and loss of pSTAT3 characterize high-grade malignancy in
      salivary gland cancer with impact on prognosis.
AB  - Increased gene copy number (high polysomy or amplification) of EGFR and HER2 has
      evolved as a predictor for response to targeted therapy. STAT3 and the apoptosis
      inhibitor survivin represent distinct oncogenes in various human neoplasms. The
      purpose of this study was to evaluate protein and gene status of these biomarkers
      by immunohistochemistry and dual color fluorescence in situ hybridization on
      tissue microarrays of 286 salivary gland carcinomas in the context of clinical
      and histopathologic characteristics. Diverse tumor types showed overexpression
      and increased gene copy number of EGFR and HER2. Amplification of HER2 was found
      in 35.5% of salivary duct carcinomas. Protein overexpression was strongly
      associated with high gene copy number for both EGFR and HER2 (P < .001).
      Overexpression and increased gene copy number of EGFR and HER2 were correlated to
      high-grade malignancy (P < .001) and unfavorable prognosis (P < .001). Strong
      nuclear staining of survivin was found in 18.9% of tumors and was associated with
      high-grade malignancy (P < .001), overexpression, and high gene copy number of
      EGFR and HER2 (P <= .05) as well as unfavorable prognosis (P < .001).
      Overexpression of nuclear pSTAT3 was found in 28.3% of tumors and correlated with
      well tumor differentiation (P < .001) and favorable prognosis (P = .001). Loss or
      weak expression of pSTAT3 was inversely associated with overexpression of
      survivin (P < .001) as well as overexpression and high gene copy number of EGFR
      and HER2 (P < .05). Overall, overexpression and increased gene copy number of
      EGFR and HER2 characterize high-grade malignancy with unfavorable prognosis in
      salivary gland cancer. Nuclear survivin typifies aggressive tumors with worse
      prognosis, whereas nuclear pSTAT3 might play a role as a tumor suppressor in
      absence of EGFR, HER2, and survivin.

PMID- 22154365
TI  - A pilot study of anatomic double-bundle anterior cruciate ligament reconstruction
      with ligament remnant tissue preservation.
AB  - PURPOSE: The purpose of this pilot study was to evaluate the preliminary results
      of an anatomic double-bundle anterior cruciate ligament (ACL) reconstruction
      procedure with ligament remnant tissue preservation. METHODS: By use of the
      transtibial technique, 2 doubled semitendinosus tendons were grafted into 4
      tunnels created at the center of each bundle attachment, penetrating the ACL
      remnant tissue. In total, 44 patients (27 male and 17 female patients) with an
      isolated ACL injury underwent ACL reconstruction with this procedure. The mean
      age of the patients was 29 years (range, 17 to 58 years). Postoperative clinical
      evaluations were performed at 16.6 months on average (range, 12 to 23 months).
      Radiologic evaluations were also performed to evaluate the tunnel location in the
      femur and the tibia. RESULTS: The mean operation time was 86 minutes (range, 72
      to 96 minutes) in the cases with ACL reconstruction only. Postoperatively, the
      mean anterior laxity was 0.7 mm. The postoperative pivot-shift test was negative
      in 81.8% of the patients, whereas there were no patients evaluated as ++. No
      patients showed any extension or flexion deficit. There were no patients
      evaluated as "nearly abnormal" or "abnormal" according to the International Knee
      Documentation Committee evaluation. The tunnel angles of the 4 tunnels were
      identical to those reported in a previous study. CONCLUSIONS: The minimal 1-year
      clinical results of anatomic double-bundle ACL reconstruction with ligament
      remnant tissue preservation were comparable to previously reported results of
      anatomic double-bundle reconstruction without remnant tissue preservation. LEVEL
      OF EVIDENCE: Level IV, therapeutic case series.

PMID- 22154366
TI  - Tubular aggregates in skeletal muscle: just a special type of protein aggregates?
AB  - Tubular aggregates are inclusions, usually found in type II muscle fibers and in
      males, consisting of regular arrays of tubules derived from the sarcoplasmic
      reticulum. Tubular aggregates are associated with a wide variety of muscle
      disorders, including poorly defined "tubular aggregate myopathies" characterized
      by weakness and/or myalgia and/or cramps, and are also present in different mouse
      models, including normal aging muscles. The mechanism(s) responsible for inducing
      the formation of these structures have not been identified, because of the slow
      time course of their development in vivo, several months in mice. However,
      identical structures are formed in a few hours in rat muscles kept in vitro in
      hypoxic medium. Here I suggest that tubular aggregates result from reshaping of
      sarcoplasmic reticulum caused by misfolding and aggregation of membrane proteins
      and thus represent a special type of "protein aggregates" due to altered
      proteostasis.

PMID- 22154367
TI  - Effects of acupuncture and exercise on insulin sensitivity, adipose tissue
      characteristics, and markers of coagulation and fibrinolysis in women with
      polycystic ovary syndrome: secondary analyses of a randomized controlled trial.
AB  - OBJECTIVE: To investigate the possible effects of low-frequency
      electroacupuncture (EA) and physical exercise on markers of coagulation and
      fibrinolysis, insulin sensitivity, and adipose tissue characteristics in women
      with polycystic ovary syndrome (PCOS). DESIGN: Secondary analyses of a
      prospective, randomized controlled clinical trial. SETTING: Department of
      Physiology and Department of Obstetrics and Gynecology, University of Gothenburg.
      PATIENT(S): Eighty-four women with PCOS were randomized. INTERVENTION(S): Women
      with PCOS were randomized to 16 weeks of low-frequency EA (14 treatments),
      physical exercise (at least 3 times/wk), or no intervention. MAIN OUTCOME
      MEASURE(S): Anthropometrics, circulating coagulation and fibrinolytic markers,
      insulin sensitivity (euglycemic hyperinsulinemic clamp), hemodynamics, and
      adipose tissue morphology/function recorded at baseline, after 16 weeks of
      intervention, and after a 16-week follow-up. RESULT(S): In the low-frequency EA
      group, circulating plasminogen activator inhibitor 1 activity decreased by 21.8%
      after 16 weeks of intervention and by 31.1% at the 16-week follow-up and differed
      from the physical exercise and the no intervention groups. The EA group had
      decreases in circulating fibrinogen and tissue plasminogen activator (t-PA),
      sagittal diameter, and diastolic blood pressure after treatment, and fibrinogen
      remained lower at the 16-week follow-up. In the physical exercise group,
      lipoprotein lipase activity increased and diastolic blood pressure decreased
      after treatment, and both diastolic and systolic blood pressure were lower at
      follow-up. No other variables were affected. CONCLUSION(S): Low-frequency EA
      counteracted a possible prothrombotic state in women with PCOS, as reflected by a
      decrease in plasminogen activator inhibitor 1 activity. Despite within-group
      improvements, there were no between-group differences in anthropometric,
      metabolic, or hemodynamic variables after 16 weeks of EA or physical exercise at
      the dose/intensity studied.

PMID- 22154368
TI  - Agonist trigger: what is the best approach? Agonist trigger and low dose hCG.
AB  - Low-dose hCG supplementation after GnRH agonist trigger may normalize
      reproductive outcome while minimizing the occurrence of OHSS in high risk IVF
      patients.

PMID- 22154369
TI  - Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with
      abnormal chromatin packaging or poor in vitro fertilization embryogenesis.
AB  - OBJECTIVE: To evaluate genome-wide DNA methylation patterns in sperm from men
      with abnormal sperm chromatin packaging and patients displaying abnormal
      embryogenesis after IVF in the absence of known female factors. DESIGN: Case
      control study. SETTING: University andrology and research laboratory. PATIENT(S):
      Men with abnormally high and low protamine 1/protamine 2 ratio (n = 15); patients
      who have undergone IVF/intracytoplasmic sperm injection resulting in abnormal
      embryogenesis (n = 13); and normozoospermic, fertile controls (n = 15).
      INTERVENTION(S): Genome-wide sperm DNA methylation was measured using the
      Illumina Infinium HumanMethylation27 BeadChip assay. Follow-up targeted
      methylation analysis was performed using bisulfite pyrosequencing. MAIN OUTCOME
      MEASURE(S): Methylation levels at more than 27,000 CpGs genome-wide were compared
      between groups. RESULT(S): Of the 43 men analyzed, 40 displayed highly concordant
      methylation patterns; however, two men with abnormal protamine 1/protamine 2 and
      one abnormal embryogenesis patient displayed significantly altered methylation
      patterns across a large number of CpGs. Imprinted regions were more prone to
      deregulation than the genome at large. CONCLUSION(S): We have identified three
      individuals displaying broad disruption of sperm DNA methylation profiles.
      Although the sample set analyzed is relatively small, these results indicate that
      broad disruptions in sperm DNA methylation may be an important signature in some
      infertile men. Functional studies will be necessary to characterize the
      developmental consequences of such epigenetic disruption.

PMID- 22154370
TI  - Antitrophoblast antibodies are associated with recurrent miscarriages.
AB  - OBJECTIVE: To investigate whether antitrophoblast antibodies are associated with
      unexplained recurrent miscarriages, we used choriocarcinoma cells JEG-3, since
      these cells are negative for class I and II antigens, but they do express HLA-G,
      resembling an antigen expression of endovascular and interstitial trophoblasts.
      DESIGN: Case-control study. SETTING: Academic research center. PATIENT(S): One
      hundred ninety-four patients with two or more consecutive, idiopathic recurrent
      miscarriages (RM; <20 weeks of gestation) were compared with 110 controls with
      normal pregnancies and without pregnancy complications. INTERVENTION(S): Anti-JEG
      3 reactivities were measured by using flow cytometry and comparisons with two in
      house standards antibody samples of low and high reactivity. MAIN OUTCOME
      MEASURE(S): Anti-JEG-3 reactivities above the 95% confidence interval of controls
      were defined as positive. RESULT(S): Sera of RM patients reacted significantly
      stronger with JEG-3 cells than that of controls. In addition, RM patients
      significantly more often had positive anti-JEG-3 reactivities (17.5%) than
      controls 5%. This difference was markedly increased with a subgroup of 80 RM
      patients who had three or more miscarriages, as 27 of these women (34%) were anti
      JEG-3 positive. CONCLUSION(S): Antitrophoblast antibodies show significantly more
      mean channel shift reactivities, and positive reactivities are significantly more
      prevalent in RM patients as compared with controls. Such antibodies may be
      involved in mechanisms affecting pregnancies.

PMID- 22154372
TI  - Granuloma annulare as first clinical manifestation of diabetes mellitus in
      children: a case report.
AB  - Granuloma annulare has been widely described in adults in association with
      systemic diseases such as type 1 diabetes mellitus. However in childhood this
      relationship remains unclear. We report the case of an 8-year-old girl, with
      multiple granuloma annulare as first clinical manifestation of type one diabetes
      mellitus.

PMID- 22154371
TI  - Superoxide dismutase content in sperm correlates with motility recovery after
      thawing of cryopreserved human spermatozoa.
AB  - OBJECTIVE: To investigate the correlation between sperm superoxide dismutase
      (SOD) content and motility recovery after thawing of cryopreserved human sperm,
      based on the rationale that this antioxidant enzyme provides protection against
      reactive oxygen species-induced damage during cryopreservation. DESIGN:
      Prospective study. SETTING: Private infertility institute and university-based
      research laboratory. PATIENT(S): Forty-two consenting normozoospermic patients
      consulting for infertility. INTERVENTION(S): The SOD content was measured in
      sperm from unfractionated samples and in sperm recovered from the pellet fraction
      obtained after discontinuous density gradient centrifugation. MAIN OUTCOME
      MEASURE(S): Sperm motility was evaluated post-thaw in the two sets of samples and
      motility recovery was plotted against the sperm SOD content to determine their
      correlation. RESULT(S): There was a significant positive correlation between
      motility recovery after thawing and SOD content in sperm from the 90% gradient
      pellet containing highly purified mature sperm. There was also a significant
      negative correlation between motility after thawing and SOD content in the
      unfractionated sample. CONCLUSION(S): The positive correlation between post-thaw
      motility recovery and SOD content in mature spermatozoa provides a good predictor
      of post-thaw motility recovery after cryopreservation.

PMID- 22154373
TI  - A systematic review of the association of diabetic retinopathy and cognitive
      impairment in people with Type 2 diabetes.
AB  - A systematic review of studies reporting data on the relationship between
      diabetic eye disease and cognitive impairment in Type 2 diabetes was conducted.
      The increase in cognitive impairment has mirrored the global increase in
      diabetes. The aim of the systematic review was to determine the level of
      association between diabetic retinopathy and cognitive impairment. Item
      selection, data extraction and critical appraisal were undertaken using standard
      procedures and independently verified by two researchers. 3 out of 10 potentially
      relevant studies were included. All studies showed a level of association between
      diabetic retinopathy and cognitive impairment, suggesting a near threefold
      increased risk of cognitive impairment in patients with diabetic retinopathy
      compared to those without. An association of cognitive impairment and severity of
      diabetic retinopathy was found in males. Diabetic retinopathy was more strongly
      linked to impairment in the cognitive domains of verbal learning and recent
      memory. An increased risk of cognitive impairment in patients with diabetic
      retinopathy was found in the reviewed studies. However, the relationship of
      severity of diabetic retinopathy and cognitive impairment has not been
      established. Further studies with standardized measurements for cognitive
      impairment and diabetic retinopathy are required to delineate this relationship
      and the role of other factors in this relationship.

PMID- 22154374
TI  - Association analysis of -429T/C and -374T/A polymorphisms of receptor of advanced
      glycation end products (RAGE) gene in Malaysian with type 2 diabetic retinopathy.
AB  - Conflicting results have been reported in different populations on the
      association between two particular RAGE gene polymorphisms (-429T/C and -374T/A)
      and retinopathy in diabetic patients. Therefore this study was designed to assess
      the association between both gene polymorphisms with retinopathy in Malaysian
      diabetic patients. A total of 342 type 2 diabetic patients [171 without
      retinopathy (DNR) and 171 with retinopathy (DR)] and 235 healthy controls were
      included in this study. Genomic DNA was obtained from blood samples and the
      screening for the gene polymorphisms was done using polymerase chain reaction
      restriction fragment length polymorphism approach. Overall, the genotype
      distribution for both polymorphisms was not statistically different (p>0.05)
      among the control, DNR and DR groups. The -429C minor allele frequency of DR
      group (12.0%) was not significantly different (p>0.05) when compared to DNR group
      (16.1%) and healthy controls (11.3%). The -374A allele frequency also did not
      differ significantly between the control and DNR (p>0.05), control and DR
      (p>0.05) as well as DNR and DR groups (p>0.05). This is the first study report on
      RAGE gene polymorphism in Malaysian DR patients. In conclusion, -429T/C and 
      374T/A polymorphisms in the promoter region of RAGE gene were not associated with
      Malaysian type 2 DR patients.

PMID- 22154375
TI  - Three-month treatment with pioglitazone reduces circulating levels of S100A8/A9
      (MRP8/14) complex, a biomarker of inflammation, without changes in body mass
      index, in type 2 diabetics with abdominal obesity.
AB  - We measured circulating S100A8/A9 (MRP8/14) complex levels before and after 3
      month treatment with pioglitazone in type 2 diabetic patients. The results showed
      that pioglitazone reduced circulating S100A8/A9 complex levels, without changing
      body mass index, in type 2 diabetic patients with abdominal obesity.

PMID- 22154376
TI  - A globally applicable screening model for detecting individuals with undiagnosed
      diabetes.
AB  - AIMS: Current risk scores for undiagnosed diabetes are additive in structure. We
      sought to derive a globally applicable screening model based on established non
      invasive risk factors for diabetes but with a more flexible structure. METHODS:
      Data from the DETECT-2 study were used, including 102,058 participants from 38
      studies covering 8 geographical regions worldwide. A global screening model for
      undiagnosed diabetes was identified through tree-structured regression analysis.
      The performance of the global screening model was evaluated in each of the
      geographical regions by receiver operating characteristic (ROC) analysis.
      RESULTS: The global screening model included age, height, body mass index, waist
      circumference and systolic- and diastolic blood pressure. Area under the ROC
      curve ranged between 0.64 in North America and 0.76 in Australia and New Zealand.
      Overall, to identify 75% of the undiagnosed diabetes cases, 49% required further
      diagnostic testing. CONCLUSIONS: We identified a globally applicable screening
      model to detect individuals at high risk of undiagnosed diabetes. The model
      performed well in most geographical regions, is simple and requires no
      calculations. This global screening model may be particularly helpful in
      developing countries with no population based data with which to develop own
      screening models.

PMID- 22154377
TI  - Lipid profile of people with diabetes mellitus type 2 and periodontal disease.
AB  - The objective of this study was to evaluate improvement of lipids and periodontal
      disease in patients with type 2 Diabetes mellitus, by means of the relationship
      between blood levels of total cholesterol and its fractions, triglycerides and
      clinical periodontal parameters. Twenty patients, in age-range 18-70 years, were
      selected and divided into 2 groups: (1) conventional periodontal scaling and root
      planing+controlled mechanic; (2) conventional periodontal scaling and root
      planing+controlled mechanical+maintenance therapy. The analyses were performed on
      day 0, 180 and 720 days, including plaque index, gingival index, probing depth
      and clinical attachment level, and evaluation of total cholesterol and its
      fractions, and triglycerides. The 2 groups presented significant reduction in
      clinical periodontal parameters, however, probing depth did not diminish
      significantly only in Group 1. There was significant improvement in all blood
      parameters in both groups. It was concluded that after 720 days of the
      experiment, there were significant improvements in clinical and blood parameters,
      in general. The group that received maintenance therapy also showed a more
      expressive improvement in clinical periodontal parameters, in general, suggesting
      that this therapy is important and necessary in patients with type 2 Diabetes
      mellitus and periodontal disease.

PMID- 22154378
TI  - The Bozola flap in oral cavity reconstruction.
AB  - The buccinator musculomucosal flaps are actually considered the main
      reconstructive option for small-moderate defects of the oral mucosa. In this
      paper we present our experience with the posteriorly based buccinator
      musculomucosal flap. A retrospective review was performed of all patients who had
      had a Bozola flap reconstruction at the Operative Unit of Maxillo-Facial Surgery
      of Parma, Italy, between 2003 and 2010. The Bozola flap was used in 19 patients.
      In most cases they had defects of the palate (n=12). All flaps were harvested
      successfully and no major complications occurred. Minor complications were
      observed in two cases. At the end of the follow up all patients returned to a
      normal diet without alterations of speech and swallowing. We consider the Bozola
      flap the first choice for the reconstruction of defects involving the palate, the
      cheek and the postero-lateral tongue and floor of the mouth.

PMID- 22154379
TI  - Advanced glycation end products contribute to the immunogenicity of IFN-beta
      pharmaceuticals.

PMID- 22154380
TI  - Frequency of mold and pollen mixing in allergen immunotherapy prescriptions
      within a large health care system, 1990-2010.

PMID- 22154381
TI  - Complete remission in 3 of 3 anti-IL-6-treated patients with Schnitzler syndrome.

PMID- 22154382
TI  - IL-13 dampens human airway epithelial innate immunity through induction of IL-1
      receptor-associated kinase M.
AB  - BACKGROUND: Impaired airway mucosal immunity can contribute to increased
      respiratory tract infections in asthmatic patients, but the involved molecular
      mechanisms have not been fully clarified. Airway epithelial cells serve as the
      first line of respiratory mucosal defense to eliminate inhaled pathogens through
      various mechanisms, including Toll-like receptor (TLR) pathways. Our previous
      studies suggest that impaired TLR2 function in T(H)2 cytokine-exposed airways
      might decrease immune responses to pathogens and subsequently exacerbate allergic
      inflammation. IL-1 receptor-associated kinase M (IRAK-M) negatively regulates TLR
      signaling. However, IRAK-M expression in airway epithelium from asthmatic
      patients and its functions under a T(H)2 cytokine milieu remain unclear.
      OBJECTIVES: We sought to evaluate the role of IRAK-M in IL-13-inhibited TLR2
      signaling in human airway epithelial cells. METHODS: We examined IRAK-M protein
      expression in epithelia from asthmatic patients versus that in normal airway
      epithelia. Moreover, IRAK-M regulation and function in modulating innate immunity
      (eg, TLR2 signaling) were investigated in cultured human airway epithelial cells
      with or without IL-13 stimulation. RESULTS: IRAK-M protein levels were increased
      in asthmatic airway epithelium. Furthermore, in primary human airway epithelial
      cells, IL-13 consistently upregulated IRAK-M expression, largely through
      activation of phosphoinositide 3-kinase pathway. Specifically, phosphoinositide 3
      kinase activation led to c-Jun binding to human IRAK-M gene promoter and IRAK-M
      upregulation. Functionally, IL-13-induced IRAK-M suppressed airway epithelial
      TLR2 signaling activation (eg, TLR2 and human beta-defensin 2), partly through
      inhibiting activation of nuclear factor kappaB. CONCLUSIONS: Our data indicate
      that epithelial IRAK-M overexpression in T(H)2 cytokine-exposed airways inhibits
      TLR2 signaling, providing a novel mechanism for the increased susceptibility of
      infections in asthmatic patients.

PMID- 22154383
TI  - Home treatment of hereditary angioedema with icatibant administered by health
      care professionals.

PMID- 22154384
TI  - A double faced ionization chamber for quality control in diagnostic radiology
      beams.
AB  - The development of new radiation detectors of low cost but with adequate
      materials is a very important task for countries that have to import ionization
      chambers such as Brazil. A special double faced ionization chamber was developed
      for use in conventional diagnostic radiology beams and computed tomography energy
      ranges. The results show that this new chamber present applicability in
      conventional diagnostic radiology and computed tomography quality control
      programs.

PMID- 22154385
TI  - Effect of lower grain sized particles on natural radiation level of the Ponnaiyar
      River sediments.
AB  - River sediment depositions on the bottom of rivers most frequently consist of
      sand and gravel particles with different grain sizes, which make them
      particularly valuable for the building construction. Knowledge of radioactivity
      present in building material enables one to assess any possible radiological
      hazard to mankind by the use of such materials. The natural radionuclide ((238)U,
      (232)Th and (40)K) contents have been analyzed for the sediment samples of
      Ponnaiyar River with an aim of evaluating the radiation hazard nature. To know
      the radiological characteristics of the sediment, dose rate is calculated and are
      compared with recommended values. Mineral characteristics of the sediments have
      been analyzed through FTIR and XRD techniques. Extinction coefficient and
      Crystallinity index is calculated to know the relative distribution of major
      minerals and crystalline nature of quartz, respectively. Multivariate statistical
      analyses were carried to find the relationship between the radioactivity
      characteristics and minerals, the results obtained in the study suggest that the
      level of natural radioactivity of the present sediments mainly depends upon the
      amount of kaolinite (clay). Mineral characterization of various grain sized
      sediments show clay and magnetic minerals are rich in lower grain sized (<= 120
      MUm) samples. The level of radioactivity has also been measured for >120 MUm
      sediments and results show that both activity concentrations and dose rate are
      considerably lowered when compared with the respective values of the bulk
      samples. The removal of <= 120 MUm particles from the sediments of the river make
      it safer to use these materials for building construction.

PMID- 22154386
TI  - Trace element measurements in high purity synthetic Al2O3 via neutron activation.
AB  - We present results from our use of thermal and fast neutron activation for the
      determination of trace elements in Al2O3 fabricated via the heat exchanger method
      (HEMTM). This material has applications in microwave oscillators and gravity-wave
      detection. Typical concentrations obtained from these measurements show the
      presence of Cr (5 ppb+20%), Ti (300 ppb+/-9.7%), Mo (1500 ppb+/-15%) and Sc (3
      ppb+/-6.7%). Details of the experiments and interpretations are given.

PMID- 22154387
TI  - Gamma-ray fast-timing coincidence measurements from the 18O+18O fusion
      evaporation reaction using a mixed LaBr3-HPGe array.
AB  - We report on a gamma-ray coincidence analysis using a mixed array of hyperpure
      germanium and cerium-doped lanthanum tri-bromide (LaBr3:Ce) scintillation
      detectors to study nuclear electromagnetic transition rates in the pico-to
      nanosecond time regime in 33,34P and 33S following fusion-evaporation reactions
      between an 18O beam and an isotopically enriched 18O implanted tantalum target.
      Energies from decay gamma-rays associated with the reaction residues were
      measured in event-by-event coincidence mode, with the measured time difference
      information between the pairs of gamma-rays in each event also recorded using the
      ultra-fast coincidence timing technique. The experiment used the good full-energy
      peak resolution of the LaBr3:Ce detectors coupled with their excellent timing
      responses in order to determine the excited state lifetime associated with the
      lowest lying, cross-shell, Ipi=4- "intruder" state previously reported in the
      N=19 isotone 34P. The extracted lifetime is consistent with a mainly single
      particle M2 multipolarity associated with a f7/2->d5/2 single particle
      transition.

PMID- 22154388
TI  - An investigation of the thermoluminescence of Ge-doped SiO2 optical fibres for
      application in interface radiation dosimetry.
AB  - We investigate the ability of high spatial resolution (~120 MUm) Ge-doped SiO2 TL
      dosimeters to measure photoelectron dose enhancement resulting from the use of a
      moderate to high-Z target (an iodinated contrast media) irradiated by 90 kVp X
      rays. We imagine its application in a novel radiation synovectomy technique,
      modelled by a phantom containing a reservoir of I2 molecules at the interface of
      which the doped silica dosimeters are located. Measurements outside of the iodine
      photoelectron range are provided for using a stepped-design that allows insertion
      of the fibres within the phantom. Monte Carlo simulation (MCNPX) is used for
      verification. At the phantom medium I2-interface additional photoelectron
      generation is observed, ~60% above that in the absence of the I2, simulations
      providing agreement to within 3%. Percentage depth doses measured away from the
      iodine contrast medium reservoir are bounded by published PDDs at 80 kVp and 100
      kVp.

PMID- 22154389
TI  - Computational analysis of irradiation facilities at the JSI TRIGA reactor.
AB  - Characterization and optimization of irradiation facilities in a research reactor
      is important for optimal performance. Nowadays this is commonly done with
      advanced Monte Carlo neutron transport computer codes such as MCNP. However, the
      computational model in such calculations should be verified and validated with
      experiments. In the paper we describe the irradiation facilities at the JSI TRIGA
      reactor and demonstrate their computational characterization to support
      experimental campaigns by providing information on the characteristics of the
      irradiation facilities.

PMID- 22154390
TI  - Three-dimensional echocardiographic characterization of patients with left
      ventricular noncompaction.
AB  - BACKGROUND: Despite several efforts using two-dimensional echocardiography and
      cardiac magnetic resonance in the diagnosis of left ventricular noncompaction
      (LVNC), there are no universally accepted diagnostic criteria. The aim of this
      study was to describe the extent of noncompacted myocardium using a new three
      dimensional echocardiographic parameter. METHODS: Seventeen patients with
      diagnoses of LVNC on the basis of two-dimensional echocardiographic and clinical
      criteria, 26 Olympic rowing athletes, and 49 healthy volunteers underwent three
      dimensional echocardiography. By offline analysis, left ventricular volumes,
      mass, ejection fraction, and sphericity index were calculated. Trabeculated left
      ventricular volume (TLV) was calculated as the difference between left
      ventricular end-diastolic volume obtained including and excluding the trabeculae
      in the cavity contour. TLV was also normalized by left ventricular end-diastolic
      volume (TLV%). RESULTS: TLV and TLV% were significantly higher in patients with
      LVNC (33.7 +/- 10.9 mL and 24 +/- 7%) as opposed to controls (7.1 +/- 2.2 mL, P <
      .001, and 6 +/- 2%, P < .001, respectively) and athletes (8.0 +/- 3.0 mL, P <
      .001, and 5 +/- 2%, P < .001, respectively). In detail, on receiver operating
      characteristic curve analysis, optimal cutoff values of 15.8 mL for TLV and 12.8%
      for TLV% were determined for the identification of LVNC (area under the curve,
      1.00; P < .001). Mild positive correlations of TLV and TLV% were found with
      sphericity index (r = 0.294, P = .004, and r = 0.301, P = .004, respectively),
      and mild negative correlations were found with ejection fraction (r = -0.454, P <
      .001, and r = -0.217, P = .038, respectively). CONCLUSIONS: Because of high
      spatial resolution and accuracy in volumetric quantification, three-dimensional
      echocardiography allows accurate measurement of the extent of noncompacted
      myocardium and identification of patients with LVNC.

PMID- 22154391
TI  - Accuracy of matrix-array three-dimensional echocardiographic measurements of
      aortic root dilation and comparison with two-dimensional echocardiography in
      pediatric patients.
AB  - BACKGROUND: Cardiac magnetic resonance imaging has demonstrated that the aortic
      root may be dilated in a dimension that two-dimensional echocardiography (2DE) is
      not able to interrogate. In the standard parasternal long-axis view, only a
      portion of the aortic root in the anteroposterior (AP) dimension can be
      visualized, as opposed to three-dimensional (3D) echocardiography (3DE), which
      can capture the entire root in an infinite number of planes. The purposes of the
      present study were to compare measurements of dilated aortic roots between 3DE
      and 2DE and to evaluate interobserver variability on 3DE. METHODS: Thirty-one
      patients (median age, 13 years) with aortic root dilation were identified. Two
      dimensional echocardiographic images and full-volume electrocardiographically
      gated 3D echocardiographic (3DE) images were obtained. Two blinded observers
      measured six dimensions of the aortic root in the short-axis view: three in the
      AP dimension and three in the transverse dimensions. Two-dimensional
      echocardiographic measurements were made by a third blinded observer. The largest
      AP 3DE measurement was compared with two-dimensional echocardiographic
      measurements. Interobserver 3DE measurements were also compared. RESULTS: The
      median aortic root Z score was +2.63. Maximum 3DE measurement in any plane of the
      root size was significantly greater than on 2DE (P < .0001). The largest AP
      dimension by 3DE was significantly greater than on 2DE (P = .001). There was no
      significant interobserver variability for the largest dimension or those in the
      AP dimension, but a difference was found in the transverse dimension (P = .02).
      CONCLUSIONS: Three-dimensional echocardiography compares favorably with 2DE in
      the evaluation of aortic root dilation in patients with known histories of aortic
      root disease. Three-dimensional echocardiography found that the largest diameter
      measured was significantly larger than on 2DE. The interobserver variability of
      3DE is low, particularly in the AP dimension and in identifying the largest
      diameter. Three-dimensional echocardiography can be a useful technique in the
      periodic surveillance of patients with aortic root dilation.

PMID- 22154392
TI  - A novel porous mechanical framework for modelling the interaction between
      coronary perfusion and myocardial mechanics.
AB  - The strong coupling between the flow in coronary vessels and the mechanical
      deformation of the myocardial tissue is a central feature of cardiac physiology
      and must therefore be accounted for by models of coronary perfusion. Currently
      available geometrically explicit vascular models fail to capture this interaction
      satisfactorily, are numerically intractable for whole organ simulations, and are
      difficult to parameterise in human contexts. To address these issues, in this
      study, a finite element formulation of an incompressible, poroelastic model of
      myocardial perfusion is presented. Using high-resolution ex vivo imaging data of
      the coronary tree, the permeability tensors of the porous medium were mapped onto
      a mesh of the corresponding left ventricular geometry. The resultant tensor field
      characterises not only the distinct perfusion regions that are observed in
      experimental data, but also the wide range of vascular length scales present in
      the coronary tree, through a multi-compartment porous model. Finite deformation
      mechanics are solved using a macroscopic constitutive law that defines the
      coupling between the fluid and solid phases of the porous medium. Results are
      presented for the perfusion of the left ventricle under passive inflation that
      show wall-stiffening associated with perfusion, and that show the significance of
      a non-hierarchical multi-compartment model within a particular perfusion
      territory.

PMID- 22154393
TI  - Molecular phylogeny and morphological evolution of the Acantharia (Radiolaria).
AB  - Acantharia are ubiquitous and abundant rhizarian protists in the world ocean. The
      skeleton made of strontium sulphate and the fact that certain harbour microalgal
      endosymbionts make them key planktonic players for the ecology of marine
      ecosystems. Based on morphological criteria, the current taxonomy of Acantharia
      was established by W.T. Schewiakoff in 1926, since when no major revision has
      been undertaken. Here, we established the first comprehensive molecular phylogeny
      from single morphologically-identified acantharian cells, isolated from various
      oceans. Our phylogenetic analyses based on 78 18S rDNA and 107 partial 28S rDNA
      revealed the existence of 6 main clades, sub-divided into 13 sub-clades. The
      polyphyletic nature of acantharian families and genera demonstrates the need for
      revision of the current taxonomy. This molecular phylogeny, which highlights the
      taxonomic relevance of specific morphological criteria, such as the presence of a
      shell and the organisation of the central junction, provides a robust
      phylogenetic framework for future taxonomic emendation. Finally, mapping all the
      existing environmental sequences available to date from different marine
      ecosystems onto our reference phylogeny unveiled another 3 clades and improved
      the understanding of the biogeography and ecology of Acantharia.

PMID- 22154394
TI  - Identification of Paramecium bursaria syngens through molecular markers-
      comparative analysis of three loci in the nuclear and mitochondrial DNA.
AB  - This is the first attempt to resolve the phylogenetic relationship between
      different syngens of Paramecium bursaria and to investigate at a molecular level
      the intraspecific differentiation of strains originating from very distant
      geographical locations. Herein we introduce a new collection of five P. bursaria
      syngens maintained at St Petersburg State University, as the international
      collection of syngens was lost in the 1960s. To analyze the degree of speciation
      within Paramecium bursaria, we examined 26 strains belonging to five different
      syngens from distant and geographically isolated localities using rDNA (ITS1-5.8S
      ITS2-5'LSU) fragments, mitochondrial cytochrome c oxidase subunit I (COI), and H4
      gene fragments. It was shown that P. bursaria strains of the same syngens cluster
      together in all three inferred molecular phylogenies. The genetic diversity among
      the studied P. bursaria strains based on rDNA sequences was rather low. The COI
      divergence of Paramecium bursaria was also definitely lower than that observed in
      the Paramecium aurelia complex. The nucleotide sequences of the H4 gene analyzed
      in the present study indicate the extent of genetic differences between the
      syngens of Paramecium bursaria. Our study demonstrates the diagnostic value of
      molecular markers, which are important tools in the identification of Paramecium
      bursaria syngens.

PMID- 22154395
TI  - Development and psychometric testing of the Ascent to Competence Scale.
AB  - AIM: This paper reports the development and psychometric testing of the Ascent to
      Competence Scale, an instrument designed to measure nursing students' perceptions
      of the quality of their clinical placement experience. BACKGROUND: The key
      purpose of clinical placements is to facilitate students' learning and progress
      toward the attainment of competence. The attainment of competence requires
      personal commitment and active involvement of students; support and guidance of
      clinical and academic staff; and clinical environments that are welcoming and
      inclusive of students. METHOD: The items for the Ascent to Competence Scale were
      identified following a critical review of the literature. Content and face
      validity were established by an expert panel. During 2010 the instrument was
      tested with third year nursing students (n=88) from one Australian university.
      Exploratory factor analysis with promax oblique rotation was used to determine
      construct validity and Cronbach's coefficient alpha determined the scale's
      internal consistency reliability. RESULTS: The final scale demonstrated
      satisfactory internal consistency (alpha 0.98). Exploratory factor analysis
      yielded a three-component structure termed "Being welcomed"; "Belongingness" and
      "Learning and competence". Each subscale demonstrated high internal consistency:
      0.89; 0.96; and 0.95 respectively. CONCLUSION: The Ascent to Competence Scale
      provides a fresh perspective on clinical placements as it allows for the
      relationship between belongingness, learning and competence to be explored. The
      scale was reliable and valid for this cohort. Further research in different
      contexts would be valuable in extending upon this work. RELEVANCE TO CLINICAL
      PRACTICE: The Ascent to Competence Scale profiled in this paper will be of
      benefit to both educational and healthcare institutions. The use of a quantified
      yardstick, such as the Ascent to Competence Scale, is important in evaluating the
      efficacy of programs, placements and partnerships between higher education and
      health services.

PMID- 22154396
TI  - Use of norethindrone acetate alone for postoperative suppression of endometriosis
      symptoms.
AB  - STUDY OBJECTIVE: To evaluate the efficacy and tolerability of norethindrone
      acetate (NA) as single-agent hormonal therapy for suppression of endometriosis
      symptoms in adolescents and young adults. DESIGN: Retrospective study. SETTING:
      Two academic medical centers. PARTICIPANTS: A keyword search using the query 'NA'
      was applied to the electronic medical records of all women treated by one
      gynecologist (M.R.L.) from 1992 to 2010. IRB-approved chart review was then
      conducted on the index records. INTERVENTIONS: Continuous treatment with NA (5-15
      mg daily). MAIN OUTCOME MEASURES: Postoperative bleeding and pain scores; adverse
      effects. RESULTS: One hundred and ninety-four patients with surgically diagnosed
      endometriosis initiated NA postoperatively during the study period. Median
      patient age was 18.9 years. 92.2% of patients had stage 1 or 2 disease, and
      distribution was similar among those excluded. Median pain scores decreased from
      5 at NA initiation to 0 at follow-up (P = .0001) and bleeding scores from 2 to 0,
      respectively (P = .001) for all stages of endometriosis. Post-NA bleeding scores
      were improved regardless of prior hormonal regimen, and post-NA pain scores
      improved in all patients except for those previously prescribed GnRH-agonist plus
      add-back. Most patients (55.2%) did not report any side effects. The most common
      adverse effect was weight gain (16.1%), with a mean increase in BMI of 1.2 +/-
      1.6 kg/m(2) at 12 months. CONCLUSION: NA alone is a well-tolerated, effective
      option to manage pain and bleeding for all stages of endometriosis. Among those
      on prior hormonal therapy, symptoms improved after NA initiation.

PMID- 22154397
TI  - Is the six-minute walk test appropriate for detecting changes in
      cardiorespiratory fitness in healthy elderly men?
AB  - OBJECTIVES: The purpose of this study was to determine whether the six-minute
      walk test (6-MWT) can detect changes in cardiorespiratory fitness (CRF) induced
      by exercise training in healthy elderly men. DESIGN: Randomized and prospective
      controlled trial. METHODS: Thirty-two healthy untrained men, between 65 and 75
      years of age, were randomly assigned to one of three groups: control (C, n = 12),
      endurance training (E, n = 10), or concurrent training (ER, n = 10). Training
      groups underwent 24 weeks of exercise, 3 times a week. All participants were
      subjected to cardiopulmonary exercise testing and the 6-MWT, before and after the
      training period. RESULTS: At follow-up, the E and ER groups had significantly
      higher peak oxygen uptake (VO(2)peak) (15.0 +/- 9.1 and 12.6 +/- 10.4%,
      respectively) and 6-MWT distances (5.5 +/- 5.3 and 4.6 +/- 2.8%, respectively)
      compared to the C group. In pre-intervention (n = 32), the 6-MWT distance
      correlated positively with (VO(2)peak) (r = 0.51, p = 0.001) and VO(2) at
      anaerobic threshold (r = 0.39, p = 0.010). On the other hand, there was no
      significant correlation between the changes (after-before) in the 6-MWT distance
      and VO(2) peak (E and ER groups: r = 0.38, p = 0.097). CONCLUSIONS: The 6-MWT is
      not appropriate to evaluate changes in CRF in healthy elderly men who performed
      endurance and concurrent training for 24 weeks.

PMID- 22154398
TI  - The presence of mandibular third molars during sagittal split osteotomies does
      not increase the risk of complications.
AB  - PURPOSE: The purpose of this study was to investigate prospectively the effects
      of the presence or absence of third molars during sagittal split osteotomies
      (SSOs) on the frequency of unfavorable fractures, degree of entrapment and
      manipulation of the inferior alveolar nerve (IAN), and procedural time. MATERIALS
      AND METHODS: The investigators designed and implemented a prospective cohort
      study and enrolled a sample composed of patients who underwent SSOs to correct
      mandibular deformities. The primary predictor variable was the status of the
      mandibular third molar at the time of SSO, and it was divided into 2 levels,
      present at the time of SSO (group I) or absent at the time of SSO (group II). The
      primary outcome variable was unfavorable splits. The secondary outcome variables
      were the degree of entrapment/manipulation of the IAN and the procedural time.
      Appropriate bivariate and multivariate statistics were computed, and the level of
      statistical significance was set at P < .05. RESULTS: Six hundred seventy-seven
      SSOs were performed in 339 patients: group I consisted of 331 SSOs (mean age +/-
      SD: 19.6 +/- 7.4 yrs), and group II consisted of 346 SSOs (30.4 +/- 12.1 yrs).
      The overall rate of unfavorable fractures was 3.1% (21 of 677), with frequencies
      of 2.4% (8 of 331) in group I, compared with 3.8% (13 of 346) in group II (P =
      .3). The rate of IAN entrapment in the proximal segment was significantly lower
      in group I (37.2%) than in group II (46.5%; P = .01). The degree of entrapment
      was also significantly more severe for group II (P < .001). Third molars
      increased procedural time by 1.7 minutes (P < .001). CONCLUSIONS: The presence of
      third molars during SSOs is not associated with an increased frequency of
      unfavorable fractures. Concomitant third molar removal in SSOs also decreases
      proximal segment IAN entrapment but only slightly increases operating time.

PMID- 22154399
TI  - Giant dermatofibrosarcoma protuberans: a case report of a surgical reconstruction
      and patient rehabilitation challenge.

PMID- 22154400
TI  - Analysis of inflammatory infiltrate, perineural invasion, and risk score can
      indicate concurrent metastasis in squamous cell carcinoma of the tongue.
AB  - PURPOSE: In this retrospective study, the aim was to compare individual
      histopathologic parameters of malignancy between nonmetastatic and metastatic
      squamous cell carcinoma of the tongue. MATERIALS AND METHODS: Sixty-two cases of
      squamous cell carcinoma of the tongue were selected and examined according to the
      system established by Brandwein-Gensler et al (Am J Surg Pathol 29:167, 2005) and
      included the pattern of invasion (most to least favorable), lymphocytic
      infiltration, perineural invasion, risk score, keratinization, eosinophilia,
      perivascular invasion, and tumor thickness. RESULTS: The least favorable pattern
      had no association with nodal metastasis (P > .05). The scarcity or density of
      the lymphocytic infiltration, perineural invasion, and a risk score >= 3 were
      associated with nodal metastasis (P < .05). Keratinization, eosinophilia,
      perivascular invasion, and tumor thickness had no association with nodal
      metastasis (P > .05). A significant positive correlation was found between the
      pattern of invasion and perineural invasion and between the pattern of invasion
      and tumor thickness (P < .05). CONCLUSIONS: The scarcity or density of the
      lymphocytic infiltration, perineural invasion, and histopathologic risk score may
      be helpful as parameters of histologic malignancy for the evaluation of
      metastatic and nonmetastatic squamous cell carcinoma of the tongue.

PMID- 22154401
TI  - Aggrandizing power output from Shewanella oneidensis MR-1 microbial fuel cells
      using calcium chloride.
AB  - There are several interconnected metabolic pathways in bacteria essential for the
      conversion of carbon electron sources directly into electrical currents using
      microbial fuel cells (MFCs). This study establishes a direct exogenous method to
      increase power output from a Shewanella oneidensis MR-1 containing MFC by adding
      calcium chloride to the culture medium. The current output from each CaCl(2)
      concentration tested revealed that the addition of CaCl(2) to 1400 MUM increased
      the current density by >80% (0.95-1.76 MUA/cm(2)) using sodium lactate as the
      sole carbon source. Furthermore, polarization curves showed that the maximum
      power output could be increased from 157 to 330 MUW with the addition of 2080 MUM
      CaCl(2). Since the conductivity of the culture medium did not change after the
      addition of CaCl(2) (confirmed by EIS and bulk conductivity measurements), this
      increase in power was primarily biological and not based on ionic effects. Thus,
      controlling the concentration of CaCl(2) is a pathway to increase the efficiency
      and performance of S. oneidensis MR-1 MFCs.

PMID- 22154402
TI  - Electrochemical oxidation of purine and pyrimidine bases based on the boron-doped
      nanotubes modified electrode.
AB  - Based on the excellent physicochemical properties of boron-doped carbon nanotubes
      (BCNTs), the electrochemical analysis of four free DNA bases at the BCNTs
      modified glassy carbon (GC) electrode was investigated. Herein, the BCNTs/GC
      electrode exhibited remarkable electrocatalytic activity towards the oxidation of
      purine bases (guanine (G), adenine (A)). More significantly, the direct oxidation
      of pyrimidine bases (thymine (T), cytosine (C)) was realized. It may be due to
      that BCNTs have the advantages of high electron transfer kinetics, large surface
      area, prominent antifouling ability and electrode activity. On basis of this, a
      novel and simple strategy for the determination of G, A, T and C was proposed.
      The BCNTs/GC electrode showed high sensitivity, wide linear range and capability
      of detection for the electrochemical determination of G, A, T, and C. On the
      other hand, the electrochemical oxidation of quaternary mixture of G, A, T, and C
      at the BCNTs/GC electrode was investigated. It was obtained that the peak
      separation between G and A, A and T, T and C were large enough for their
      potential recognition in mixture without any separation or pretreatment. The
      BCNTs/GC electrode also displayed good stability, reproducibility and excellent
      anti-interferent ability. Therefore, it can be believed that the BCNTs/GC
      electrode would provide a potential application for the electrochemical detection
      of DNA in the field of genetic-disease diagnosis.

PMID- 22154403
TI  - Nano-magnetic primer based electrochemiluminescence-polymerase chain reaction
      (NMPE-PCR) assay.
AB  - Here we have developed a novel nano-magnetic primer based
      electrochemiluminescence-polymerase chain reaction (NMPE-PCR) strategy for
      detection of genome. The key idea of this method is integrating the two in situ
      processes: PCR on the surface of magnetic nanoparticles (MNPs) and magnetic beads
      based ECL readout platform, to avoid some laborious manual operations and achieve
      rapid yet sensitive detection. At first, the approach employs a pair of
      functional primers for amplification: one is tris-(2,2'-bipyridyl) ruthenium
      (TBR) labeled primer; the other one is nano-magnetic primer which is prepared by
      attaching the primer to the surfaces of MNPs. With the presence of DNA analyte
      and PCR mixture, the TBR labeled products are directly loaded and enriched on the
      surface of MNPs during PCR cycling. Then the MNPs-TBR complexes can be analyzed
      by a magnetic ECL platform without any post-modification or post-incubation.
      Finally, we used Listeria monocytogenes as the target to examine these desirable
      properties of this assay, reaching a detection limit of 500 fg/MUL for genome in
      1 h. The proposed study has provided the evidence as a proof-of-concept, thus
      having potential for development of automatic mode for detection of specific
      gene.

PMID- 22154404
TI  - Ultrasensitive and selective non-enzymatic glucose detection using copper
      nanowires.
AB  - In the pursuit of more economical electrocatalysts for non-enzymatic glucose
      sensors, one-dimensional Cu nanowires (Cu NWs) with uniform size distribution and
      a large aspect ratio (>200) were synthesized by a facile, scalable, wet-chemistry
      approach. The morphology, crystallinity, and surface property of the as-prepared
      Cu NWs were examined by SEM, XRD, and XPS, respectively. The electrochemical
      property of Cu NWs for glucose electrooxidation was thoroughly investigated by
      cyclic voltammetry. In the amperometric detection of glucose, the Cu NWs modified
      glassy carbon electrode exhibited an extraordinary limit of detection as low as
      35 nM and a wide dynamic range with excellent sensitivity of 420.3 MUA cm(-2) mM(
      1), which was more than 10,000 times higher than that of the control electrode
      without Cu NWs. The performance of the developed glucose sensor was also
      independent to oxygen concentration and free from chloride poisoning.
      Furthermore, the interference from uric acid, ascorbic acid, acetaminophen,
      fructose, and sucrose at the level of their physiological concentration were
      insignificant, indicating excellent selectivity. Finally, good accuracy and high
      precision for the quantification of glucose concentration in human serum samples
      implicate the applicability of Cu NWs in sensitive and selective non-enzymatic
      glucose detection.

PMID- 22154405
TI  - 17beta-estradiol prevents reduction of retinal phosphorylated 14-3-3 zeta protein
      levels following a neurotoxic insult.
AB  - Previous studies demonstrated the substantial protective role of 17beta-estradiol
      (E2) in several types of neuron, although its mechanism of action remains to be
      elucidated. In this study, we found that the levels of 14-3-3 zeta mRNA and
      phosphorylated and total 14-3-3 zeta proteins were significantly decreased in the
      rat retina after intravitreal injection of N-methyl-d-aspartate (NMDA). 17beta-E2
      implantation significantly inhibited NMDA-induced decreases in phosphorylated but
      not in total 14-3-3 zeta protein levels in the retina. There was a decrease in
      both phosphorylated and total 14-3-3 protein levels in RGC-5 cells, a retinal
      ganglion cell line, after glutamate and buthionine sulfoximine (BSO) exposure,
      and 17beta-E2 treatment significantly inhibited only the decrease in
      phosphorylated but not in total 14-3-3 zeta protein levels. The cell viability
      assay showed substantial cell death after glutamate and BSO exposure and that
      17beta-E2 treatment significantly protects against this cell death. 17beta-E2
      treatment also significantly increased the level of phosphorylated 14-3-3 protein
      in RGC-5 cells without other treatments. These results suggest that a decrease in
      14-3-3 zeta expression may be associated with retinal neurotoxicity induced by
      NMDA or the combination of glutamate and BSO. The regulation of 14-3-3 zeta
      phosphorylation is one possible mechanism of the protective effect of 17beta-E2
      in the retina.

PMID- 22154407
TI  - Role of dopamine D3 receptors in basal nociception regulation and in morphine
      induced tolerance and withdrawal.
AB  - Repeated administration of opioids such as morphine leads to the development of
      tolerance to their pain-relieving effects as well as to physical dependence.
      Although the association between the dopamine system and the molecular mechanisms
      of morphine-induced antinociceptive tolerance has been studied, the possible
      interaction between morphine-induced tolerance and D3 receptors has not been
      investigated. In the present study, male mice lacking the dopamine D3 receptor
      gene were used to investigate the function of D3 receptors in the development of
      morphine-induced tolerance and withdrawal. Compared with wild-type (WT) mice, the
      dopamine D3 receptor knockout (D3R KO) mice showed pronounced hypoalgesia. The
      D3R KO mice clearly developed lower morphine-induced tolerance and showed
      attenuated withdrawal signs compared with the WT mice. These results suggest that
      D3 receptors regulate basal nociception and are involved in the development of
      morphine-induced tolerance and withdrawal.

PMID- 22154406
TI  - Repetition learning of vibrotactile temporal sequences: an fMRI study in blind
      and sighted individuals.
AB  - The present fMRI study examined cortical activity to repeated vibrotactile
      sequences in 11 early blind and 11 sighted participants. All participants
      performed with >90% accuracy and showed practice induced improvement with faster
      reaction times in identifying matched and unmatched vibrotactile sequences. In
      blind only, occipital/temporal and parietal/somatosensory cortices showed
      practice induced reductions in positive BOLD amplitudes that possibly reflected
      repetition induced learning effects. The significant findings in occipital cortex
      of the blind indicated that perceptual processing of tactile inputs in visually
      deprived cortex is dynamic as response amplitudes changed with practice. Thus,
      stimulus processing became more efficient. It was hypothesized that the changes
      in occipital cortex of the blind reflected life-long skill in processing
      somatosensory inputs. Both groups showed activity reductions with practice in
      mid/posterior ventrolateral prefrontal cortex. These activity reductions
      suggested common stimulus-response learning associations for vibrotactile
      sequences in mid/posterior ventrolateral prefrontal cortex.

PMID- 22154408
TI  - Literature review and practical aspects on the management of oxaliplatin
      associated toxicity.
AB  - Colorectal cancer is currently a public health priority because it is the second
      leading cause of cancer deaths in Western countries. Combination regimes of
      oxaliplatin and infusional fluorouracil/leucovorin or capecitabine have emerged
      as important options in the palliative and adjuvant treatment of colorectal
      cancer. Although better tolerated than cisplatin, oxaliplatin displays a
      characteristic profile of adverse events whose recognition and management are
      essential for physicians who treat patients with colorectal cancer and other
      malignancies that benefit from the use of oxaliplatin. Peripheral neuropathy is
      probably the most frequent and clinically relevant adverse event associated with
      the use of oxaliplatin, and several measures have been proposed to mitigate this
      toxicity. Temporary interruption of oxaliplatin before limiting neurotoxicity
      develops during therapy is a potential approach to avoid the problem of
      oxaliplatin-associated neuropathy in patients with metastatic colorectal cancer.
      Calcium and magnesium infusions have no effect on chemotherapy efficacy and also
      constitute a useful approach in clinical practice. Finally, the incidence and
      severity of chronic peripheral neuropathy in patients treated with oxaliplatin
      may be reduced by the use of neuroprotective agents, for example, venlafaxine.
      Other adverse events, such as gastrointestinal and liver toxicity,
      thrombocytopenia, and hypersensitivity reactions, are also reviewed in this
      article, and suggestions are made for their management.

PMID- 22154409
TI  - Endoscopic treatment of paraesophageal abscess in eosinophilic esophagitis after
      chest trauma.

PMID- 22154410
TI  - Stent-in-stent technique for removal of a metal stent embedded in the colon wall
      by using a fully covered, self-expandable metal esophageal stent (with video).

PMID- 22154411
TI  - Endoscopic mucosal ablation: a new argon plasma coagulation/injection technique
      to assist complete resection of recurrent, fibrotic colon polyps (with video).
AB  - BACKGROUND: Incomplete piecemeal EMR of large, sessile/flat colon polyps results
      in polyp recurrence, with massive submucosal scarring making subsequent attempts
      at endoscopic resection problematic. OBJECTIVE: We report our experience with a
      new endoscopic mucosal ablation (EMA) technique that can be used to complement
      the eradication of recurrent fibrotic colon polyps. DESIGN: Single-center,
      retrospective case series. SETTING: Tertiary-care referral academic endoscopy
      unit. PATIENTS: This study involved consecutive patients referred for endoscopic
      excision of recurrent benign colon polyps with severe submucosal fibrosis (>30%
      of the entire lesion). INTERVENTION: Application of high-power argon plasma
      coagulation (APC), preceded by injection of a submucosal fluid cushion (normal
      saline/diluted adrenaline and/or sodium hyaluronate solution) to protect the
      muscle layer, was performed to augment further piecemeal EMR and polyp
      eradication. MAIN OUTCOME MEASUREMENTS: Technical safety and success,
      complication and recurrence rates. RESULTS: Fourteen patients (mean age 73 years;
      9 men, 5 women) with 15 recurrent colon adenomas (mean polyp size 30 mm, 9
      proximal/6 distal) were included. EMA with a mean APC power setting of 55 W was
      applied. Complete polyp eradication was achieved in 9 of 11 patients (82%) at
      first or second completed follow-up. One patient needed laparoscopic colectomy
      because of cancer, and 1 underwent transanal endoscopic microsurgery for benign
      massive recurrence. The other 3 patients with small, easily treatable recurrence
      (<=3 mm) were followed by 1-year-surveillance. No perforations and no
      postpolypectomy syndrome were reported. LIMITATIONS: Single-center, nonrandomized
      case series with short duration follow-up. CONCLUSION: EMA appears to be a safe
      and easily applicable technique to assist the complete eradication of recurrent
      fibrotic colon polyps.

PMID- 22154412
TI  - Validation of a novel method for assessing competency in polypectomy.
AB  - BACKGROUND: There is a gap in the formal assessment of technical skills in
      polypectomy that is now considered an integral part of colonoscopy. Polypectomy
      has been shown to reduce the incidence of colorectal cancer but does have
      associated complications. Polypectomy competency assessment should arguably be a
      part of the certification process for all endoscopists. A polypectomy competency
      assessment tool (Direct Observation of Polypectomy Skills [DOPyS]) has been
      developed and its reliability examined. This study examined the ability of the
      DOPyS to reliably distinguish between endoscopists with different levels of
      experience, ie, its construct validity. OBJECTIVE: To determine the construct
      validity of the DOPyS. DESIGN: Videos of 32 polypectomies (endoscopic view only)
      were collected from 2 expert (> 1000 colonoscopies) endoscopists (17 polyps) and
      6 intermediate-level (100-500 colonoscopies) endoscopists (15 polyps). The videos
      were edited to include only the entire polypectomy procedure, arranged in random
      order, and assessed blindly by 4 experienced endoscopists, only 2 of whom were
      familiar with polypectomy assessment by using the DOPyS before scoring. The
      differences in overall competency scores (range 1-4; competency, scores >= 3) for
      the expert and intermediate groups were compared by using the Fisher exact test.
      SETTING: Single center. RESULTS: The analysis suggested that both trained
      assessors familiar with the DOPyS could reliably distinguish between the expert
      and intermediate endoscopists (P = .049 and P < .001), with the expert group
      scoring higher than the intermediate one. For the assessors with no previous
      experience of the DOPyS, no such difference could be seen (P = .71 and P = .15).
      LIMITATIONS: Small sample and polyp size. CONCLUSIONS: The results of the
      analysis suggested that the DOPyS could reliably differentiate between
      polypectomies performed by endoscopists of different levels of experience, but
      only if the assessors were trained in the use of the assessment tool. Training is
      therefore required to use this tool reliably.

PMID- 22154413
TI  - Fistulization in the GI tract in acute pancreatitis.

PMID- 22154414
TI  - Cantaloupe melon-like stomach.

PMID- 22154415
TI  - Diagnostic and therapeutic peroral direct cholangioscopy in patients with altered
      GI anatomy (with videos).

PMID- 22154416
TI  - Endoscopic stenting is not as effective for palliation of colorectal obstruction
      in patients with advanced gastric cancer as emergency surgery.
AB  - BACKGROUND: Although self-expandable metal stent (SEMS) insertion has been shown
      to be an effective therapy for palliation of obstruction from colorectal
      malignancy, the clinical efficacy of SEMS insertion in the palliation of
      colorectal obstruction from an extracolonic malignancy (ECM) has not been
      extensively evaluated. OBJECTIVE: The aim of this study was to evaluate the
      clinical outcomes and complications of SEMSs compared with those of emergency
      surgery for relief of colorectal obstruction in patients with advanced gastric
      cancer (AGC). DESIGN: Retrospective study. PATIENTS: From January 2000 to
      December 2009, patients with AGC who were treated with SEMSs (N = 111) or
      emergency surgery (N = 69) for palliation of malignant colorectal obstruction
      were included. INTERVENTION: SEMS insertion or surgery. RESULTS: Although acute
      complications and stoma formations were lower in the SEMS group than in the
      surgery group, the clinical efficacy of SEMSs was inferior to emergency surgery
      (technical success, 73.9% vs 94.2%, P = .001; clinical success, 54.1% vs 75.4%, P
      = .005). SEMS-related complications occurred in 64.5%, including reobstruction
      (36.8%), stent migration (10.5%), perforation (13.2%), and bleeding (3.9%). The
      median duration of patency was not statistically different between the patients
      who underwent SEMS insertion and those who underwent emergency surgery (117 days
      vs 183 days, P = .105). Patients with fewer than 2 obstructive sites or less than
      2 years to obstructive symptom onset after diagnosis of AGC showed better
      clinical outcomes after endoscopic stenting. LIMITATIONS: Retrospective and
      single-center study. CONCLUSIONS: SEMS insertion seems to be less effective than
      emergency surgery for the palliation of colorectal obstruction in patients with
      AGC. Further study is necessary to define those patients with ECM who may benefit
      from SEMS insertion.

PMID- 22154418
TI  - Jaundice and abdominal pain in a patient with hemobilia secondary to a right
      hepatic artery subsegmental arteriovenous malformation.

PMID- 22154417
TI  - Blinded nonrandomized comparative study of gastric examination with a
      magnetically guided capsule endoscope and standard videoendoscope.
AB  - BACKGROUND: Passive video capsule endoscopy is the criterion standard for small
      bowel exploration but cannot be used for the large gastric cavity. We report the
      first blinded comparative clinical trial in humans comparing a magnetically
      guided capsule endoscope (MGCE) and a conventional high-definition gastroscope.
      OBJECTIVE: To assess the potential of gastric examination with a guided capsule.
      DESIGN: Blinded, nonrandomized comparative study. SETTING: Single endoscopy
      center. METHODS: The trial involved 61 patients included in a blinded capsule and
      gastroscopy comparative study. MGCE examination was performed 24 hours after
      patients had undergone gastroscopy. To remove food residue or mucus, patients
      drank 900 mL of water in 2 portions. Then to provide the air-water interface
      required by the guidance system, they drank 400 mL of water at 35 degrees C.
      RESULTS: Visualization of the gastric pylorus, antrum, body, fundus, and cardia
      was evaluated as complete in 88.5%, 86.9%, 93.4%, 85.2%, and 88.5% of patients,
      respectively. Of gastric lesions, 58.3% were detected by both gastroscopy and
      MGCE at immediate assessment and review of recorded data. Capsule examination
      missed 14 findings and gastroscopy missed 31 findings seen with MGCE. Overall
      diagnostic yield was similar for both modalities. LIMITATION: Pilot study.
      CONCLUSIONS: Diagnostic results were similar for the 2 methods. After some
      technical difficulties related to gastric expansion or presence of mucus had been
      overcome, this study opened a new field for noninvasive gastric examination in
      countries where high gastric cancer incidence demands a screening tool.

PMID- 22154419
TI  - Principles of training in GI endoscopy.

PMID- 22154420
TI  - Health workers at the core of the health system: framework and research issues.
AB  - This paper presents a framework for the health system with health workers at the
      core. We review existing health-system frameworks and the role they assign to
      health workers. Earlier frameworks either do not include health workers as a
      central feature of system functioning or treat them as one among several
      components of equal importance. As every function of the health system is either
      undertaken by or mediated through the health worker, we place the health worker
      at the center of the health system. Our framework is useful for structuring
      research on the health workforce and for identifying health-worker research
      issues. We describe six research issues on the health workforce: metrics to
      measure the capacity of a health system to deliver healthcare; the contribution
      of public- vs. private-sector health workers in meeting healthcare needs and
      demands; the appropriate size, composition and distribution of the health
      workforce; approaches to achieving health-worker requirements; the adoption and
      adaption of treatments by health workers; and the training of health workers for
      horizontally vs. vertically structured health systems.

PMID- 22154421
TI  - Interaction of 5-Fluorouracil and its derivatives with bovine serum albumin.
AB  - Fluorouracil (5-FU) and its derivatives are the most commonly used drugs to treat
      many types of cancer. Two dual functional agents, FUPAE and FUPAP, derived from 5
      Fluorouracil (5-FU) have shown radiosensitizing activity but unlike their
      components were not cytotoxic. This study was designed to examine the interaction
      of BSA with 5-Fluorouracil (5-FU) and two of its derivatives; FUPAE and FUPAP at
      physiological conditions, using a constant protein concentration and various drug
      contents. FTIR, UV-Vis spectroscopic methods as well as molecular modelling were
      used to determine the drugs binding mode, the binding constants and the effects
      of drug complexation on BSA stability and conformation. Structural analysis
      showed that 5-Fluorouracil, FUPAE and FUPAP bind BSA via polypeptide polar groups
      with overall binding constants of K(5-FU-BSA)=3.02(+/-0.09)*10(3), K(FUPAE
      BSA)=1.08(+/-0.04)*10(4), K(FUPAP-BSA)=1.21(+/-0.06)*10(4) M(-1). BSA
      conformation was altered by a major reduction of alpha-helix from 69% (free BSA)
      to 34% with 5-FU, 40% with FUPAE, 38% with FUPAP. These results suggest that
      serum albumins might act as carrier proteins for FUPAE and FUPAP in delivering
      them to target tissues.

PMID- 22154422
TI  - [Rebleeding from a vertebral artery dissection in a child: an inflammatory
      vasculopathy?].
AB  - We present a case of a rebleeding remote from a vertebral artery dissection
      associated with subarachnoid haemorrhage. A 7-year-old boy without any antecedent
      presented a traumatic dissection of the vertebral artery with subarachnoid
      haemorrhage. After a conservative treatment, the morphology of the vertebral
      artery became normal and the boy was asymptomatic. Four months later, a
      rebleeding occurred on the same vertebral artery, whose morphological review was
      normal. Mechanisms and cases of rebleeding in the literature are discussed. An
      inflammatory vasculopathy was suspected and discussed.

PMID- 22154423
TI  - [Chronic subdural hematoma infected by Campylobacter fetus: case report].
AB  - We report here a rare case of chronic subdural hematoma infected by Campylobacter
      fetus in a 86-year-old woman. She was admitted for confusion and disorientation
      in a context of high fever and diarrhoea. After two surgeries, the evolution was
      finally good with a combination of antibiotics (amoxicillin and clindamycin).
      Chronic subdural hematoma is a potential site for bacterial infection. Our case
      suggests that C. fetus infection should be suspected in elderly patients
      presenting with fever and enteritis. The frequency of such cases may be
      underestimated, due to the difficult diagnosis of C. fetus. It is also suspected
      that C. fetus could play a role in the recurrence of hematoma, because of its
      vessel tropism.

PMID- 22154424
TI  - Stratigraphic and technological evidence from the Middle Palaeolithic
      Chatelperronian-Aurignacian record at the Bordes-Fitte rockshelter (Roches
      d'Abilly site, Central France).
AB  - This paper presents a geoarchaeological study of Middle and Upper Palaeolithic
      (Chatelperronian, Aurignacian and Solutrean) occupations preserved at the Bordes
      Fitte rockshelter in Central France. The lithostratigraphic sequence is composed
      of near-surface sedimentary facies with vertical and lateral variations, in a
      context dominated by run-off and gravitational sedimentary processes. Field
      description and micromorphological analysis permit us to reconstruct several
      episodes of sediment slope-wash and endokarst dynamics, with hiatuses and
      erosional phases. The archaeostratigraphic succession includes Chatelperronian
      artefacts, inter-stratified between Middle Palaeolithic and Aurignacian
      occupations. Systematic refitting and spatial analysis reveal that the
      Chatelperronian point production and flake blanks retouched into denticulates,
      all recovered in the same stratigraphic unit, result from distinct and successive
      occupations and are not a 'transitional' Middle to Upper Palaeolithic assemblage.
      The ages obtained by (14)C place the Chatelperronian occupation in the 41-48 ka
      cal BP (calibrated thousands of years before present) interval and are consistent
      with the quartz optically stimulated luminescence age of 39 +/- 2 ka and feldspar
      infra-red stimulated luminescence age of 45 +/- 2 ka of the sediments. The Bordes
      Fitte rockshelter sequence represents an important contribution to the debate
      about the characterization and timing of the Chatelperronian, as well as its
      affinities to earlier and later industries.

PMID- 22154425
TI  - Monorchiids (Platyhelminthes: Digenea) of chaetodontid fishes (Perciformes):
      biogeographical patterns in the tropical Indo-West Pacific.
AB  - Species richness and biogeography of the monorchiid genus Hurleytrematoides was
      studied by the examination of 2834 individuals of 45 species of Chaetodontidae at
      six major sites in the tropical Indo-West Pacific: Heron Island, Lizard Island,
      Ningaloo (Western Australia), Palau, New Caledonia and Moorea (French Polynesia).
      In total, 18 species were distributed among six sites; descriptions are provided
      for eight new species: H. boucheti n. sp., H. combesi n. sp., H. deblocki n. sp.,
      H. dollfusi n. sp., H. euzeti n. sp., H. kulbickii n. sp., H. pasteuri n. sp.,
      and H. planesi n. sp. Overall richness ranged from zero to five Hurleytrematoides
      species per chaetodontid species. Seven Hurleytrematoides species were found at
      only one locality and eleven were found at multiple localities. Only one species,
      H. morandi, was found at all localities. Individual localities had between six
      (Moorea) and 10 (Heron Island) species; we attribute Moorea's depauperate
      parasite fauna to its isolation and distance from the Indo-Philippine centre of
      biological diversity. Using cluster analysis of 18 species of Hurleytrematoides
      and 45 species of chaetodontids sampled in the Indo-West Pacific, we show that
      the localities on the Great Barrier Reef (Heron Island and Lizard Island) and New
      Caledonia have the most similar chaetodontid and parasite fauna of any locality
      pairs. Cluster analysis results also show that the similarity of the chaetodontid
      assemblages at five of the six localities is relatively high and that Ningaloo
      has the most distinct fauna. Similarity values based on sharing of species of
      Hurleytrematoides are generally lower than those for their hosts; Moorea,
      Ningaloo and Palau all have low similarity to New Caledonia and Great Barrier
      Reef sites. We attribute these distinctions to the differential dispersal
      capability of the fish and their parasites. Chaetodontids have long-lived mobile
      pelagic larvae, the dispersal of which would be most affected by prominent
      biogeographical barriers, such as that between the Indian and Pacific Oceans. In
      contrast, monorchiids have no obvious dispersal stage, and vast distances have
      the capacity to act as effective barriers to dispersal. We conclude that the
      present distributions of species of Hurleytrematoides in the Indo-Pacific are
      driven by historical opportunity and capacity to disperse, and that some disjunct
      distributions are sculpted by stochasticity.

PMID- 22154426
TI  - Expression of NOS and VEGF in feline mammary tumours and their correlation with
      angiogenesis.
AB  - In order to define the role of nitric oxide (NO) in feline mammary tumours, the
      expression of endothelial or inducible nitric oxide synthase (e/iNOS) and
      vascular endothelial growth factor (VEGF), and their relationship with
      angiogenesis, was investigated in 23 feline mammary tumours (two hyperplastic, 19
      adenocarcinoma, one osteosarcoma and one squamous cell carcinoma) by
      immunohistochemistry. Tumour angiogenesis was assessed by CD31 immunostaining and
      was expressed as microvessel density (MVD). In general, iNOS immunoreactivity was
      localised in tumour cells and occasionally in stromal myofibroblasts, whereas
      eNOS and VEGF were localised in the cytoplasm of tumour epithelial cells and
      endothelium. In malignancy, expression of iNOS increased from well- to less
      differentiated phenotypes (Grades 1-3) and was significantly higher in G3 and G2
      when compared with G1 cases. However, increasing eNOS expression was limited only
      in hyperplastic lesions and showed no significant changes among the grades. In
      addition, expression of iNOS was positively correlated with VEGF and MVD in
      feline mammary tumours and both measures were significantly greater in less
      differentiated phenotypes (P<0.05). In conclusion, the expression of NOS isoforms
      in feline mammary tumours depended on tumour grade, and the positive correlations
      between iNOS and angiogenic markers suggests that iNOS synthesised by tumour
      cells promotes tumour growth. Thus, iNOS can be used as an important
      immunohistochemical marker to determine the degree of malignancy and prognosis of
      feline mammary carcinoma.

PMID- 22154427
TI  - Forearm bone mineral density measurement with different scanning positions: a
      study in right-handed Chinese using dual-energy X-ray absorptiometry.
AB  - The purpose of our study was to determine whether different scanning positions
      influence forearm bone mineral density (BMD) measurements and to evaluate the
      association between forearm BMDs in different scanning positions and those of
      other skeleton sites. The study population consisted of 30 right-handed healthy
      Chinese volunteers. BMD was measured with GE Lunar Prodigy at the left forearm in
      both sitting and supine positions, and at lumbar spine and the right femur. All
      subjects received repeated measurements in the same day (repositioning), and the
      average of repeated BMD results was used for analysis. The BMD precision errors
      of the nondominant forearm in the sitting and supine positions varied from 1.13%
      to 2.46%. There were no statistically significant differences between BMD
      precision errors for each region of interest (ROI) between sitting and supine
      positions (all the p values were greater than 0.05). When comparing BMDs on the
      same side in the sitting position with those in the supine position, there were
      significant differences at both the 1/3 radius level and in the total radius
      (p<0.05). The BMD values at these ROIs obtained in the supine position were lower
      than those in the routine sitting position. The BMDs of the ultradistal radius in
      the both 2 different scanning positions were significantly associated with lumbar
      spine and femoral neck BMD, respectively. The total radius BMD in the different
      positions was associated with the BMD of the femoral neck. A change in body
      scanning position from sitting to supine will significantly influence forearm BMD
      results.

PMID- 22154428
TI  - Establishment of age-specified bone mineral density reference range for Indian
      females using dual-energy X-ray absorptiometry.
AB  - We undertook this study to establish age-specified bone mineral density (BMD)
      reference range for Indian females using dual-energy X-ray absorptiometry. BMD at
      multiple skeletal sites was measured in 2034 healthy women aged 18--85yr. The
      effect of anthropometry and biochemical parameters on BMD was determined. Peak
      BMD was observed between 30 and 35yr at the hip, lumbar spine, and radius.
      Significant positive correlation of height and weight with BMD was observed at
      33% radius, femur neck, and lumbar spine, whereas significant negative
      correlation was seen between serum alkaline phosphatase (ALP) and serum
      parathyroid hormone levels with BMD at aforementioned sites. On multivariate
      regression analysis, age, weight, and serum ALP were the most consistent
      contributors to variance in the BMD. Compared with age-matched US females, BMD of
      lumbar spine was significantly lower for our subjects in all age groups.
      Prevalence of osteoporosis among women aged older than 50yr was significantly
      higher based on Caucasian T-scores as opposed to using peak BMD/standard
      deviation values from the population under review at lumbar spine but not at
      femoral neck.

PMID- 22154429
TI  - Which to use to evaluate change in BMD at follow-up: RMS-SD or RMS-%CV?
AB  - There is bias toward the use of root-mean-square standard deviation (RMS-SD) over
      root-mean-square coefficient of variation (RMS-%CV) to calculate a least
      significant change (LSC) value that is used to determine if change in bone
      mineral density (BMD) at follow-up is statistically significant. In part, this
      bias is based on the assumption that SD is relatively constant over a wide range
      of BMD as opposed to %CV, which is assumed to increase as BMD decreases. However,
      evidence to support these assumptions is scant. The purpose of this project was
      to determine the frequency of discrepancies in interpretation of follow-up data
      using an LSC based on RMS-SD (LSC-SD) vs RMS-%CV (LSC-%CV). A convenience sample
      of 100 patients returning for follow-up dual-energy X-ray absorptiometry scans
      was used to compare the frequency of change in BMD exceeding LSC-SD vs LSC-%CV.
      Results showed that agreement in exceeding (or not) both LSC-SD and LSC-%CV was
      94% for L1-L4 (lumbar spine), femoral neck, and total hip. Disagreements were
      characterized by BMD changes that usually marginally exceeded either LSC-SD or
      LSC-%CV but not the other, and they occurred at both high and low absolute BMD.
      We conclude that significant change in BMD typically exceeds both LSC-SD and LSC
      %CV. Thus, there seems to be no basis for the bias in favor of using LSC-SD as
      long as RMS-SD and RMS-%CV are calculated in the same manner. Furthermore, a
      criterion that both LSC-SD and LSC-%CV must be exceeded may help avoid
      overcalling marginal change as being significant, especially at high and low BMD.

PMID- 22154430
TI  - Importance of ethnic base standard references for the diagnosis of osteoporosis
      in Thai women.
AB  - Many studies demonstrated the importance of using ethnic-specific normal database
      in the diagnosis of osteoporosis (OP). Aims of this study were to assess
      diagnostic agreement, prevalence of OP, and diagnostic misclassification between
      Caucasian, Japanese, and Thai normal databases. The cross-sectional study of 3181
      Thai women who had bone mineral density (BMD) measurement between January 2008
      and December 2010 was performed. BMDs at lumbar spine (LS), femoral neck (FN),
      and total hip (TH) were derived to T-score by using Caucasian, Japanese, and Thai
      standard references. Kappa statistic was used to assess diagnostic agreement and
      misclassification. Diagnostic agreements between Caucasian and Thai reference
      databases were 0.39 for LS and 0.90 for FN. No statistical agreement was found in
      TH region (0.01, p value=0.264). Applying the Japanese reference, diagnostic
      agreements were 0.71 for LS, 0.76 for FN, and 0.94 for TH regions. Prevalence of
      OP in postmenopausal women was 64.1%, 37.7%, and 41.4% using Caucasian, Japanese,
      and Thai standard references. Percentage of misclassification was varied by
      menopausal status and reference database from 11.2% to 48.7%. When applying
      Japanese databases instead of Caucasian normal databases, overall diagnostic
      misclassification decreased from 35.1% to 16.1%. Choice of reference database has
      a significant effect on the diagnosis of low bone mass and OP. Japanese reference
      database has better diagnostic agreement with previously studied Thai reference
      database in 1999 than Caucasian reference database.

PMID- 22154431
TI  - Complicated osteoporosis in progeroid syndrome: treatment with teriparatide.
AB  - Human progeroid syndromes (PSs) include a group of genetic "premature aging"
      diseases that affect a variety of organ systems. Bone diseases are common
      sequelae of patients diagnosed with PSs. Teriparatide therapy is recommended for
      elderly men with low bone mineral density (BMD; T-score <-2.5) and at least 1
      fragility fracture who are unable to tolerate bisphosphonates. We describe a 20
      yr-old patient affected by PS and severe osteoporosis complicated with femoral
      fracture. The patient experienced a significant improvement in lumbar spine BMD
      after treatment with teriparatide.

PMID- 22154432
TI  - Bone metabolism in cholestatic children before and after living-related liver
      transplantation--a long-term prospective study.
AB  - Bone disorders are common in children with end-stage liver diseases, especially
      those associated with cholestasis. Abnormal hepatocyte function, disordered
      vitamin D metabolism and calcium-phosphorous homeostasis, malnutrition, and
      immunosuppressive treatment are potential risk factors of bone tissue pathology
      before and after transplantation. The aim of the study was to analyze the long
      term effect of successful living-related liver transplantation (LRLTx) on
      skeletal status and bone metabolism in cholestatic children. Eighteen cholestatic
      children (1.4+/-0.5yr old; 12 females [F]/6 males [M]) qualified for LRLTx were
      analyzed; 16 (5F/11M) of them participated in long-term observation (V4). Serum
      levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP),
      cross-linked telopeptide of type 1 collagen (CTx), insulin-like growth factor I
      (IGF-I), IGF-I binding protein 3 (IGFBP-3), parathyroid hormone (PTH), 25
      hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were
      assayed before (V0) and 6mo (V1), 12mo (V2), 18mo (V3), and 4.4yr (V4) after
      LRLTx. Total body bone mineral content (TBBMC) and total body bone mineral
      density (TBBMD) were measured by dual-energy X-ray absorptiometry (DXA) at the
      same pattern. Before LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 levels as well
      as TBBMC and TBBMD were decreased compared with age-matched control group. The
      mean serum levels of 25(OH)D and 1,25(OH)(2)D were within reference ranges from
      V0 to V4. After LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 as well as TBBMC and
      TBBMD reached the age-matched reference values. At V4, the level of P1NP
      decreased below and the PTH increased above the reference range that coincided
      with reduced Z-scores of both TBBMC (-1.11+/-1.24) and TBBMD (-1.00+/-1.19). P1NP
      and CTx, both measured at V3, correlated with IGF-I at V2 (R=0.86, p=0.014 and
      R=0.78, p=0.021, respectively) and PTH at V3 for P1NP and V1 for CTx (R=0.64,
      p=0.048 and R=0.54, p=0.038, respectively). The TBBMC changes between V0 and V4
      correlated with IGF-I (R=0.68, p=0.015) and 1,25(OH)(2)D (R=0.54, p=0.025), both
      assayed at V1. The change of TBBMC Z-scores between V0 and V4 correlated with
      P1NP at V1 (R=0.69, p=0.002). The TBBMD changes between V0 and V4 correlated with
      CTx at V1 (R=0.54, p=0.027) and P1NP change between V0 and V1 (R=0.51, p=0.038).
      In short-term observation, successful LRLTx led to bone metabolism normalization
      triggered by probable anabolic action of IGF-I and PTH and manifested by TBBMC
      and TBBMD increases. In long-term horizon, moderately impaired DXA assessed bone
      status coincided with disturbances in bone metabolism. Bone metabolism markers,
      especially P1NP and CTx, appeared to be good predictors of changes in bone status
      evaluated by DXA.

PMID- 22154433
TI  - Evaluation of bone mineral density in postmenopausal women in Kuwait.
AB  - Menopause is the major risk factor for the loss of bone mineral density (BMD) and
      bone mineral content (BMC) in women. In this study, we determined the prevalence
      of osteoporosis in postmenopausal women in Kuwait and compared it with that of
      other Middle East and west countries. Two thousand two hundred ninety-six
      postmenopausal women ranging in age from 40 to 87yr were included in the study
      and divided into 4 age groups by decade. We measured body weight, height, body
      mass index (BMI), BMD, and BMC. The mean age, height, and weight were 59.1+7.9yr,
      154.7+6.5cm, and 77.3+14.9kg, respectively. The mean BMI and BMC were
      32.4+6.6kg/m(2) and 0.9+0.14g/cm(2), respectively. The average T-scores for the
      hip and lumbar spine were -0.280+1.2 and -1.297+1.33, respectively. BMC
      significantly decreased with age from 0.95 to 0.81g/cm(2). Four hundred forty
      four (19.3%) were found to have osteoporosis. The incidence of osteoporosis
      significantly increased from 4.3% to 39.9% with age, which is lower than that
      reported for Saudi (40%) and Moroccan women (39.6%) and higher than that for
      US/European (31%) and Lebanese women (11%).

PMID- 22154434
TI  - Association of bone mineral density, parameters of bone turnover, and body
      composition in patients with chronic obstructive pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) often develop
      osteoporosis. Many hormones regulate bone metabolism and body composition, and
      some of them are affected in COPD patients vs controls. In 46 COPD patients, we
      measured hip neck, total hip, lumbar spine, and whole-body T-score with dual
      energy X-ray absorptiometry, parameters of body composition (body mass index
      [BMI], fat mass index [FMI], and fat-free mass index [FFMI]), and adiponectin,
      leptin, parathormone, osteocalcin, calcitonin, and insulin-like growth factor I
      (IGF-I) serum levels and correlated them with COPD stage. Our results suggest
      that total hip bone mineral density (BMD) is affected by FFMI and COPD stage;
      lumbar spine BMD is affected by FMI and COPD stage; and whole-body BMD is
      affected by BMI, COPD stage, and leptin. Adiponectin, parathormone, osteocalcin,
      calcitonin, and IGF-I levels were not significantly correlated to BMD at any of
      the measured sites. Our findings are in agreement with the current literature in
      that a decline in lung function is correlated to a decline in BMD.

PMID- 22154435
TI  - Estimation of stature from static and dynamic footprints.
AB  - The ability to estimate accurately from known parameters is a fundamental aspect
      of science and is evident as an emerging approach in the area of footprints and
      stature estimation within the field of forensic identification. There are
      numerous foot dimensions that have been measured in the literature to predict
      stature with varying degrees of confidence but few studies have tried to link the
      strength of estimation to anatomical landmarks. Such an approach is utilised in
      this study which estimates stature from the right footprints of sixty one adult
      male and female UK participants. Static and dynamic footprints were taken from
      each volunteer using the 'inkless paper system'. The prints were digitised and
      twelve length, width and angle measurements were chosen for the analysis. The
      highest correlations with stature were shown to be the heel to fourth toe print
      for the static group of footprints (r=0.786, p<0.01), and the heel to fifth toe
      print in the dynamic footprints (r=0.858, p<0.01). Collinearity statistics
      suggest the heel to fifth toe print length measurement is independent and not
      influenced by any other variables in the estimation of stature for the dynamic
      prints. Linear regression equations for this measurement presented the smallest
      standard error of estimate (SEE) and highest shared variance (R(2)) of all
      included variables (SEE 4.16, R(2) 0.74). Our study discusses a potential
      anatomical explanation as to why the lateral border of the foot and hence the
      impression it makes upon a hard surface, is a more stable indicator in the
      estimation of stature. The investigation recommends the use of Calc_A4 and
      Calc_A5 length measurements when estimating stature from footprint impressions.

PMID- 22154436
TI  - An assessment of early mandibular growth.
AB  - Quantification of skeletal data has been shown to be an effective and reliable
      method of demonstrating variation in human growth as well as for monitoring and
      interpreting growth. In South Africa as well as internationally, few researchers
      have assessed mandibular growth in late fetal period and early childhood and
      therefore standards for growth and age determination in these groups are limited.
      The purpose of this study was to evaluate growth in the mandible from the period
      of 31 gestational weeks to 36 months postnatal. A total of 74 mandibles were
      used. Dried mandibles were sourced from the Raymond A. Dart Collection
      (University of Witwatersrand), and cadaveric remains were obtained from the
      Universities of Pretoria and the Witwatersrand. The sample was divided into four
      groups; 31-40 gestational weeks (group 1), 0-11 months (group 2), 12-24 months
      (group 3), and 25-36 months (group 4). Twenty-one osteological landmarks were
      digitized using a MicroScribe G2. Ten standard measurements were created and
      included: the maximum length of mandible, mandibular body length and width,
      mandibular notch width and depth, mental foramen to inferior border of mandible,
      mandibular basilar widths bigonial and biantegonial, bigonial width of mental
      foramen and mental angle. Data were analyzed using PAST statistical software and
      Morphologika2 v2.5. Statistically significant differences were noted in the
      linear measurements for all group comparisons except between groups 3 and 4. The
      mandible morphologically changed from a round, smooth contour anteriorly to adopt
      a more sharp and narrow adult shape. A progressive increase in the depth and
      definition of the mandibular arch was also noted. In conclusion, the mandible
      initially grows to accommodate the developing tongue (up to 11 months),
      progressive dental eruption and mastication from 12 to 36 months. Mastication is
      associated with muscle mass development; this would necessitate an increase in
      the dimensions of the mandibular notch and associated muscle attachment sites.
      These findings might be valuable in the estimation of age in unidentified
      individuals and to monitor prenatal growth of the mandible for the early
      diagnosis of conditions associated with stunted mandibular growth.

PMID- 22154437
TI  - Midline facial soft tissue thickness database of Turkish population: MRI study.
AB  - Facial reconstruction is the approximation of an antemortem face from human
      skeletal remains. Since the nineteenth century, several methods have been
      developed for reconstruction of the face; all of them require the measurement of
      average tissue thicknesses at various points on the face. To our knowledge, there
      are no publications on soft tissue thickness in the Turkish population. In
      addition, there are few publications on the value of magnetic resonance imaging
      (MRI) in measuring soft tissue thickness for forensic sciences. The aim of this
      study was to create a reference database of facial tissue thickness in the
      Turkish population, and to present data illustrating the successful use of MRI
      for this purpose. The study included 161 patients (79 males and 82 females)
      between the ages of 18 and 78 who had undergone brain MRI in our radiology
      clinic, and showed no sign of maxillofacial pathology. Measurements were taken at
      9 points at the midline; glabella, nasion, end of nasals, mid-philtrum, upper lip
      margin, lower lip margin, chin-lip fold, mental eminence, and beneath chin
      points. The mean values for these points in the patient sample population were
      determined, and differences related to age, sex, and body mass index (BMI) were
      calculated. The values were then compared to the findings of the Manhein study.

PMID- 22154438
TI  - Cross-reactivities of various phenethylamine-type designer drugs to immunoassays
      for amphetamines, with special attention to the evaluation of the one-step urine
      drug test Instant-ViewTM, and the Emit(r) assays for use in drug enforcement.
AB  - Cross-reactivities of 76 kinds of phenethylamine-type designer drugs and related
      compounds to the urine drug tests Instant-View TM (IV) (the Methamphetamine (MA)
      test, the Amphetamine 300 test, and the MDMA test) have been investigated. An on
      site urine test kit consisting of these three IV tests has been evaluated for the
      on-site screening of MA users, and the kit has been found to have satisfactory
      specificity for drug enforcement purposes by separately detecting both MA and its
      metabolite amphetamine. The cross-reactivity profiles of Emit((r)) II Plus
      Amphetamines Assay, Emit((r)) II Plus Ecstasy assay, and Emit((r)) d.a.u.((r))
      Amphetamine Class assay have also been investigated and discussed.

PMID- 22154439
TI  - Zygomaticomaxillary suture shape analyzed with digital morphometrics: reassessing
      patterns of variation in American Indian and European populations.
AB  - Typological classification of human zygomaticomaxillary suture (ZMS) shape is
      often used in forensic assessment of ancestry, following earlier studies
      reporting higher frequencies of "angled" sutures among American Indians and
      higher frequencies of "curved" sutures among Caucasians. In this paper we present
      a new method of digital morphometrics to quantify and compare ZMS shape in 60
      American Indian and 60 European crania. Suture outlines were recorded as three
      dimensional (3D) contours on digital models of adult male and female crania
      created with a portable 3D laser scanner. Each contour was represented by about
      four hundred point coordinates, which were transformed via Fourier analysis into
      amplitude coefficients suitable for use in linear discriminant analysis.
      Discriminant functions were created that accurately predicted group membership
      for 83% of the crania in the sample, after leave-one-out cross-validation. The
      results were compared with traditional typological classifications based on
      visual evaluation of ZMS shape, and the contour-based method was found to be more
      effective than the typological approach. However, the distribution of ZMS types
      within the two sample groups did not conform to previously reported patterns.
      This discrepancy indicates that ZMS shape may reflect not only genetic factors,
      but also environmental factors such as diet and stress. In addition, some
      evidence for sexual dimorphism in the zygomaticomaxillary complex was observed.
      Based on these findings, we recommend caution when using ZMS shape analysis in
      forensic ancestry determination.

PMID- 22154440
TI  - [Drug vial labeling and medication errors in anaesthesia: do these features break
      up?].

PMID- 22154441
TI  - [Cricothyrotomy for airways management: current data and interest for combat
      casualty care].
AB  - OBJECTIVES: To detail current data in cricothyrotomy and imperatives of airway
      management in combat casualty care. METHODS: Review of the literature in Medline
      database over the past 40 years. RESULTS: Modern armed conflicts, including
      guerrilla and terrorism, have changed the approach of tactical combat casualty
      care. The first medical support must be as close as possible to the battlefield,
      reducing casualties thanks to a quick intervention. Because of a lack of
      physicians on the battlefield, the first operator is often a paramedical staff
      trained to simple lifesaving procedures. The orotracheal intubation remains the
      gold standard for airways management, but often impossible because of the
      environmental factors of the battlefield. Therefore, cricothyrotomy may become an
      interesting choice in this case and not only an alternative for orotracheal
      intubation like in civilian practice. It provides an easy and safe underglottis
      airways access by a laryngotomy between the cricoid and the thyroid cartilages.
      Performed by paramedical staff, it is a strictly protocolized delegated medical
      prescription. CONCLUSION: This review of literature and the analysis of
      commercial kits prompt us to suggest safe methods that can be performed on
      battlefield. Surgical methods and MiniTrach II kit (Portex) seem to be
      particularly suitable for battlefield situations. An airways management algorithm
      for combat casualty care is also proposed.

PMID- 22154442
TI  - [Peroperative anaphylactic shock in children: management and evaluation].
AB  - Anaphylactic shock is the most severe manifestation of hypersensitivity, whether
      of allergic origin or not. In the operating theatre, anaphylactic shock is rare
      in paediatric patients and latex allergy is still the major cause of allergy.
      Whatever the cause and mechanism of the reaction, its treatment should be started
      as early as possible: a high level of suspicion is thus necessary to establish a
      diagnosis as early as possible. Symptomatic treatment is well codified. The
      results of blood sampling at the time of the reaction and of allergic tests
      performed a few weeks later will enable a definitive diagnosis to be made and
      appropriate recommendations (medical alert card) to be given to the patients and
      its parents.

PMID- 22154443
TI  - An information campaign on aminoglycosides use during septic shock failed to
      improve the quality of care.
AB  - BACKGROUND: Septic shock remains a major cause of death in intensive care units
      (ICU) and an inappropriate antibiotic regimen worsens the prognosis. The aim of
      the study was to assess the impact of an information campaign on modalities of
      prescription of aminoglycosides in septic shock. STUDY DESIGN: A prospective
      observational study. METHODS: Consecutive septic shock patients admitted to the
      surgical ICU over a 2-year period were included. An information campaign allowed
      to differentiate between a pre- (P1) and a post- (P2) interventional period. The
      campaign clarified the rules and requirements for pharmacological monitoring of
      aminoglycosides. The main objective was to increase the rate of prescription of
      peak serum aminoglycoside following the first intravenous injection. RESULTS: One
      hundred and forty-eight patients (P1=76 and P2=72) were finally included into the
      study. Similar clinical characteristics were observed during both periods. The
      rate of prescription of peak serum aminoglycoside following the first injection
      was performed in 49% (P1) versus 65% (P2), P=0.09. The length of stay in ICU was
      16 days [extremes: 1-74] (P1) versus 17 days [extremes: 1-133] (P2) (P=0.84).
      Inhospital mortality was 28% (P1) versus 26% (P2), P=0.86. CONCLUSIONS: An
      information campaign describing the modalities of prescription of aminoglycosides
      in septic shock failed to improve medical practices and patient outcomes. A
      mobile team of antibiotics could be useful in daily practice.

PMID- 22154444
TI  - [Oesophago-gastro-duodenoscopy in a teenager and esophageal achalasia].
AB  - Oesophago-gastro-duodenoscopy for diagnostic is daily performed in adults and in
      children during sedation with propofol. This is administrated in France by
      anaesthesiologists. Pulmonary or cardiovascular complications are rare. We report
      a case of massive inhalation during an EGD with a teenager. The assessment has
      revealed an oesophageal achalasia, a condition rare in children and atypical
      development. This case highlights the importance of systematic screening for risk
      of a full stomach during the anaesthesia consultation, and the difficulty in
      evaluation in case of medical migrant patient.

PMID- 22154445
TI  - [Anaesthetic management of the Wolf-Hirschhorn syndrome: a report of two cases].

PMID- 22154446
TI  - [Ischaemic stroke secondary to viper envenomation in Morocco in the absence of
      adequate antivenom].
AB  - An ischaemic stroke is a rare complication of viper envenomation that is due to
      multifactorial pathophysiological mechanisms. The authors describe the case of a
      55-year-old patient bitten by the viper Cerastes cerastes. The patient was
      admitted to the intensive care unit with multiple organ failure, disseminated
      intravascular coagulopathy, rhabdomyolysis, anuria and elevated troponin level.
      The persistent disturbance of consciousness has motivated a brain scan which has
      revealed a bifocal ischemic stroke. The complex venom of the species C. cerastes
      may induce hypotension, tissue necrosis, acute renal failure, bleeding disorders
      or DIC. With the cessation of a non-indicated heparintherapy and haemodialysis,
      the patient recovered in a few weeks despite the initial infusion of an
      unsuitable antivenom due to the late identification of the reptile. The
      preventive treatment of the complications of this envenomation is based on the
      infusion of the polyvalent antivenom Favirept((r)).

PMID- 22154447
TI  - [Second wave of the French drug harmonisation programme to prevent medication
      errors: overall appreciation of healthcare professionals].
AB  - BACKGROUND: Medication errors are a significant cause of severe healthcare
      associated complications. In December 2006, the French Health Products Agency
      (Afssaps) has issued a protocol to harmonise labeling of injectable drugs vials.
      In 2007, a first change was launched for four drugs and was followed in 2008-2009
      by a second wave concerning 42 active drugs. METHODS: The present study describes
      how healthcare professionals have perceived this change and their overall
      appreciation of the drug harmonisation programme. A survey using an electronic
      questionnaire was distributed to medical and non-medical professionals in
      anaesthesia and intensive care and pharmacists in a representative sample of 200
      French hospitals. RESULTS: The harmonisation procedure was felt as being overall
      satisfactory by 53% of professionals who had responded but it was recognised that
      the new procedure is associated with improved readability and understanding of
      drug dosage. The use of colour coding was also well accepted by the personnel of
      clinical units. Respondents expressed significant criticisms regarding both the
      communication plan and the way the plan was implemented locally in hospitals. Old
      and new labeling coexisted in 66% of responding hospitals and many respondents
      described being aware of errors or near-misses that were considered related to
      the transition. For many important topics, pharmacists had views that were
      significantly different from clinicians. CONCLUSION: This national survey
      describing the perception of healthcare professionals regarding the new
      harmonisation procedure for injectable drugs highlighted some progress but also a
      number of deficiencies, notably regarding communication and implementation of the
      change in clinical units. This survey will be used by the French Health Products
      Agency to improve future steps of the long-lasting campaign against medication
      errors.

PMID- 22154448
TI  - [Epidural analgesia for surgical treatment of peritoneal carcinomatosis: a risky
      technique?].
AB  - BACKGROUND: To study the risks of haemodynamic instability, and the possible
      occurrence of spinal haematoma, meningitis and epidural abscess when epidural
      analgesia is performed for cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy (HIPEC). METHODS: We retrospectively analyzed the data of 35
      patients treated by HIPEC with oxaliplatin or cisplatin. An epidural catheter was
      inserted before induction of general anaesthesia. Postoperatively, a continuous
      epidural infusion of ropivacain, then a patient-controlled epidural analgesia
      were started. RESULTS: The epidural catheter was used peroperatively before HIPEC
      in 12 subjects (34%), and after HIPEC in 23 subjects (66%). The median dose of
      ropivacain given peroperatively in the epidural catheter was 40 mg (30-75).
      Norepinephrin was used in two subjects (6%) peroperatively (median infusion rate
      0.325 MUg/kg per minute [0.32-0.33]), and in four subjects (11%) in the
      postoperative 24 hours. No spinal haematoma, meningitis or epidural abscess were
      noted. Five subjects (14%) had a thrombopenia or a prothrombin time less than 60%
      before catheter removal. Two subjects (6%) had a leukopenia before catheter
      removal. No thrombopenia or blood coagulation disorders were recorded the day of
      catheter removal. CONCLUSION: In this series of 35 patients, the use of epidural
      analgesia for HIPEC does not seem to be associated with a worse risk of
      haemodynamic instability, spinal haematoma, meningitis or epidural abscess. HIPEC
      with platinum salt is not incompatible with the safety of epidural analgesia,
      with an optimized fluid management peroperatively and the following of
      perimedullary anesthesia practice guidelines.

PMID- 22154449
TI  - [Dissection of the descending aorta complicated by preeclampsia at 30 weeks of
      gestation: medical treatment and caesarean delivery].
AB  - The authors report the case of a dissection of the descending thoracic aorta in a
      woman in the third trimester of the pregnancy. After an initial medical therapy
      by a combination of three intravenous anti-hypertensive medications, a caesarean
      section was decided under general anaesthesia at 30 weeks of gestation as the
      result of the occurrence of a severe preeclampsia. The aetiology, diagnosis, and
      anaesthetic management are discussed.

PMID- 22154450
TI  - [What is new regarding anaesthetic monitoring in the operating room?].
AB  - This paper critically reviews the new devices that can be used on the operating
      room to monitor the oxygenation and the haemodynamics of the child undergoing
      general anaesthesia.

PMID- 22154451
TI  - [Rapid sequence induction in a patient with Steinert myotonic dystrophy: Interest
      of the association of high doses of rocuronium and sugammadex].
AB  - We report in this clinical case the successful use of a combination of rocuronium
      and sugammadex in a patient with Steinert myotonic dystrophy to perform a rapid
      sequence induction of anaesthesia. The patient had both contraindication to
      succinylcholine and a risk of prolonged neuromuscular blockade with non
      depolarizing neuromuscular blocking agents. The use of high dose rocuronium
      (1mg/kg) allowed a quick and easy orotracheal intubation but induced a prolonged
      neuromuscular block, reversed with success by sugammadex (8 mg/kg).

PMID- 22154452
TI  - [Pharmaco-economic aspects of perioperative pain management].
AB  - We present a reflection on pharmaco-economy of perioperative pain management. A
      real optimisation of expenses could be obtained if taking into consideration
      factors that augment and diminish costs of the process, due to the organisation
      of the process itself, due to optimisation of the information and decision's
      circuits. The cost of an analgesic is not significant when compared with the cost
      of entire process of pain management.

PMID- 22154453
TI  - [Factors associated with non-compliance to surgical antimicrobial prophylaxis
      guidelines during a prospective audit].
AB  - OBJECTIVES: To assess physician compliance with guidelines for surgical
      antimicrobial prophylaxis practices and to identify factors associated with non
      compliance. PATIENTS AND METHOD: In a prospective study of patients admitted for
      clean or clean contaminated surgery from February 1 to April 28, 2008, we
      assessed appropriateness of surgical antimicrobial prophylaxis indication
      (recommended and prescribed or not recommended and not prescribed) and
      administration (antimicrobial choice, dose, timing and duration). Overall
      compliance was achieved if all criteria of indication and administration were
      met. The overall non-compliance rate was estimated and was used as a dependent
      variable in a multivariate logistic regression analysis to identify factors
      associated with non-compliance. RESULTS: In a total of 481 practices evaluated,
      appropriateness of indication and administration of surgical prophylaxis were
      respectively 83% and 56%. The overall compliance rate to guidelines for surgical
      antimicrobial prophylaxis was 37%. In a multivariate regression analysis,
      prescription of antimicrobial prophylaxis by a surgeon (RR: 3.4; CI 95%: 1.6
      7.5), clean-contaminated surgery (RR: 2.2; CI 95%: 1.4-3.7), traumatology surgery
      (1.87; 1.1-3.3), digestive surgery (3.7; 1.8-7.5) and head or neck-related
      surgery (11.4; 2.3-56.3) were independent factors associated with non-compliance
      to guidelines for surgical antimicrobial prophylaxis. CONCLUSION: This study
      confirmed previous findings on the impact of the type of surgery and the wound
      class contamination on the overall compliance rate. Furthermore, non-compliance
      was related to surgeon prescriptions. The compliance should be improved by
      specific measures after professional feedback.

PMID- 22154454
TI  - [Intracerebral haemorrhage and postpartum cerebral angiopathy associated with the
      administration of sulprostone and norepinephrine].
AB  - We report the case of a 29-year-old female who had developed a postpartum
      cerebral angiopathy (PCA) complicated by an intracerebral haematoma and
      convulsions, after a postpartum haemorrhage with sulprostone and norepinephrine
      infusion. PCA is an under diagnosed neurovascular pathology, responsible of
      reversible and non-specific symptoms. However, it can be complicated by
      haemorrhagic or ischemic stroke with vital or functional risks. As PCA is favored
      by vasoactive treatments, their administration in peripartum period, when it is
      imperative, should be strictly controlled.

PMID- 22154455
TI  - [Anaesthetic management for caesarean delivery and acute myocardial infarction by
      spontaneous coronary dissection].
AB  - Myocardial infarction is rare during pregnancy and is associated with a high
      maternal and foetal mortality rate. We report the case of a 32-year-old woman at
      38 weeks gestation who developed a myocardial infarction with spontaneous
      coronary dissection treated with coronary angioplasty and who needed an emergency
      caesarean section. We discuss the anaesthetic management of urgent caesarean
      section in this context.

PMID- 22154456
TI  - [A new complication related to prolonged prone position: a masseter muscle
      haematoma].
AB  - We report a case of a 54-year-old man who underwent an prolonged spinal
      osteosynthesis complicated by a masseter muscle compressive ischaemia and
      haematoma in the early postoperative period. A special attention of the body
      compressive points in particular of the face, in association with an horseshoe's
      headstall, would have probably lead to avoid this complication in this risk
      factors patient.

PMID- 22154457
TI  - Electromembrane extraction using stabilized constant d.c. electric current--a
      simple tool for improvement of extraction performance.
AB  - This contribution presents an experimental approach for improvement of analytical
      performance of electromembrane extraction (EME), which is based on the use of
      stabilized constant d.c. electric current. Extractions were performed using a
      high voltage power supply, which provided stabilized constant d.c. current down
      to 1MUA and facilitated current-controlled transfer of ions of interest from a
      donor solution through a supported liquid membrane (SLM) into an acceptor
      solution. Repeatability of the extraction process has significantly improved for
      EME at constant electric current compared to EME at constant voltage. The
      improved repeatability of the extraction process was demonstrated on EME
      capillary electrophoresis (EME-CE) analyses of selected basic drugs and amino
      acids in standard solutions and in human urine and serum samples. RSD values of
      peak areas of the analytes for EME-CE analyses were about two-fold better for EME
      at constant electric current (2.8-8.9%) compared to EME at constant voltage (3.6
      17.8%). Other analytical parameters of the EME-CE methods, such as limits of
      detection, linear ranges and correlation coefficients were not statistically
      different for the two EME modes. Moreover, EME at constant electric current did
      not suffer from SLM instabilities frequently observed for EME at constant
      voltage.

PMID- 22154458
TI  - International conference on human biomonitoring, Berlin 2010.

PMID- 22154459
TI  - Development of national human biomonitoring programme in Slovenia.
AB  - In Slovenia patchy human biomonitoring (HBM) data have been collected over the
      past three decades, mainly in areas polluted with lead, mercury or
      polychlorinated biphenyls (PCBs). In 2007, the National Institute of Public
      Health (NIPH) prepared a proposal for the national HBM programme based on the
      initiatives and recommendations of the World Health Organisation, the
      International Programme on Chemical Safety and the European Environment and
      Health Action Plan 2004-2010. In the absence of national reference values we
      proposed an initial two year cross-sectional environmental epidemiological study
      aiming to establish national reference values for selected chemicals in blood of
      320 subjects; i.e. 40 males, and in blood and milk of 40 breastfeeding first time
      mothers, aged 20-35 years living in each of the four unpolluted areas, and
      fulfilling other specific inclusion and exclusion criteria. In the next two
      phases, inhabitants of other regions including heavily contaminated hot spots
      will be studied, thus involving in total 960 subjects in six years. We selected
      the following chemicals: benzene, cadmium, fluoride, lead, mercury,
      organochlorine pesticides, and a range of polybrominated dyphenyl ethers,
      polychlorinated dibenzo dioxins, polychlorinated dibenzo furans and PCB
      congeners. The selection criteria were based on national air and soil monitoring
      results, toxicological hazard of chemicals, their persistence and bioaccumulation
      potential, estimated size of exposed populations, analytical capacity, certain
      public concerns, and trends in other countries. In order to help the
      identification of exposure sources we also proposed the contents of a detailed
      questionnaire to be completed by the participants. The first results were
      expected in 2010, but are not yet available. We expect that the results will
      provide a base to determine the national reference values, exposure of adults to
      selected chemicals irrespective of exposure route and exposure of babies via
      maternal milk, to establish the geographical differences in exposure, to identify
      and evaluate the sources of exposure, to compare the data internationally, as
      well as generate data for risk assessment, risk reduction measures, and indicate
      the needs for further studies.

PMID- 22154460
TI  - Clinical review--breast adenoid cystic carcinoma.
AB  - OBJECTIVES: To review the published literature on the diagnosis and management of
      adenoid cystic carcinoma (ACC) of the breast. MATERIALS AND METHODS: Papers were
      identified by searching PubMed using the terms " adenoid cystic carcinoma " and "
      breast ". Additional papers were identified by reviewing references of relevant
      articles. RESULTS: ACC of the breast is a rare tumour comprising less than 0.1%
      of breast malignancies. Its cellular origin in the breast remains unclear. The
      histological characteristics of ACC in the breast are similar to those of ACC of
      the salivary glands. However the prognosis of ACC of the breast is better than
      that of other localizations with prolonged survival. Breast-conserving treatment
      including postoperative radiotherapy seems to be equivalent to mastectomy alone
      with respect to survival. The value of adjuvant systemic therapies is not
      established. Late relapses can occur, so long-term follow-up is mandatory for
      these patients. CONCLUSIONS: ACC of the breast has a favourable prognosis. An
      accurate diagnosis and appropriate treatment are therefore important.

PMID- 22154461
TI  - Anthropometric measures and fasting insulin levels in children before and after
      cure of Cushing syndrome.
AB  - BACKGROUND & AIMS: Children with Cushing syndrome present with growth delay and
      excess adiposity that tends to be generalized rather than centripetal. There are
      no prospective studies of this phenotype as it evolves before and after treatment
      in children. The aims of this study were to evaluate children prior to and one
      year after surgical cure compared to controls and to determine fasting insulin
      levels and their possible association with waist circumference and waist-height
      ratio, pre- and post-cure of Cushing syndrome. METHODS: 30 children with Cushing
      syndrome were evaluated prior to and one-year post-treatment and compared to 14
      age and body mass index-matched controls. RESULTS: Only triceps skin fold z-
      score showed a significant difference between patients with active Cushing
      syndrome and controls. A positive correlation between fasting insulin levels and
      waist circumference z- score was found for children with Cushing syndrome; this
      association persisted one-year following cure. CONCLUSIONS: Unlike adults
      affected with Cushing syndrome, upper arm muscle area of children with Cushing
      syndrome did not differ from obese children without Cushing syndrome. The
      persistence of a positive correlation between waist circumference and fasting
      insulin despite remission of Cushing syndrome suggests that children with a
      history of Cushing syndrome may have an increased risk for adverse long-term
      effects of increased abdominal fat mass.

PMID- 22154462
TI  - Pegylated interferon-alpha2b and ribavirin combination therapy induces
      Hashitoxicosis followed by type 1 diabetes mellitus.
AB  - The combination of pegylated interferon-alpha2b (PEG-IFNalpha) and ribavirin
      (RBV) is a standard treatment for chronic hepatitis C. The case of a patient with
      chronic hepatitis C who developed Hashitoxicosis followed by type 1 diabetes
      mellitus (T1DM) with PEG-IFNalpha plus RBV combination therapy, but not IFNalpha
      alone, is presented.

PMID- 22154463
TI  - Measuring health-related quality of life in diabetic peripheral neuropathy: a
      systematic review.
AB  - We undertook a systematic review of disease-specific measures of health-related
      quality of life (HRQL) in diabetic peripheral neuropathy (DPN) to appraise the
      scientific (psychometric) evidence and make recommendations about the best
      instrument(s) to use. DPN is a common complication of diabetes mellitus. A need
      to consider the broad impact of DPN, rather than just pain and the increasingly
      recognised need to assess patient-reported outcomes such as HRQL in evaluating
      healthcare has led to a demand for rigorous outcome measures. To identify
      appropriate disease-specific measures, we searched four databases: PubMed,
      Embase, PsycINFO and CINAHL Plus. Data were extracted from each article using a
      standard data extraction form and the psychometric properties of each HRQL
      measure were reviewed. We identified three DPN-specific measures of HRQL: PN-QOL
      97, Norfolk QOL-DN, NeuroQoL. All three measures satisfy at least one criterion
      for both reliability and validity, though all also have some disadvantages. Where
      there is no requirement for multi-language versions, the PN-QOL-97 is a useful
      instrument. Studies that involve multiple languages would need to use the shorter
      QOL-DN but would also need to incorporate complementary instruments to address
      the psychological and emotional impact of DPN.

PMID- 22154465
TI  - Neuromuscular manifestations of viscoelastic tissue degradation following high
      and low risk repetitive lumbar flexion.
AB  - Cumulative lumbar disorder is common in individuals engaged in long term
      performance of repetitive and static occupational/sports activities with the
      spine. The triggering source and of the disorder, the tissues involved in the
      failure and the biomechanical, neuromuscular, and biological processes active in
      the initiation and development of the disorder are not known. The hypothesis is
      forwarded that static and repetitive (cyclic) lumbar flexion-extension and the
      associated repeated stretch of the various viscoelastic tissues (ligaments,
      fascia, facet capsule, discs, etc.) causes micro-damage in their collagen fibers
      followed by an acute inflammation, triggering pain and reflexive muscle
      spasms/hyper-excitability. Continued exposure to activities, over time, converts
      the acute inflammation into a chronic one, viscoelastic tissues
      remodeling/degeneration, modified motor control strategy and permanent
      disability. Changes in lumbar stability are expected during the development of
      the disorder. A series of experimental data from in-vivo feline is reviewed and
      integrated with supporting evidence from the literature to gain a valuable
      insight into the multi-factorial development of the disorder. Prolonged cyclic
      lumbar flexion-extension at high loads, high velocities, many repetitions and
      short in between rest periods induced transient creep/laxity in the spine, muscle
      spasms and reduced stability followed, several hours later, by an acute
      inflammation/tissue degradation, muscular hyper-excitability and increased
      stability. The major findings assert that viscoelastic tissues sub-failure damage
      is the source and inflammation is the process which governs the mechanical and
      neuromuscular characteristic symptoms of the disorder. A comprehensive model of
      the disorder is presented. The experimental data validates the hypothesis as well
      as provide insights into the development of potential treatment and prevention of
      the disorder.

PMID- 22154464
TI  - IL-6 contributes to an immune tolerance checkpoint in post germinal center B
      cells.
AB  - The generation of a B cell repertoire involves producing and subsequently purging
      autoreactive B cells. Receptor editing, clonal deletion and anergy are key
      mechanisms of central B cell tolerance. Somatic mutation of antigen-activated B
      cells within the germinal center produces a second wave of autoreactivity; but
      the regulatory mechanisms that operate at this phase of B cell activation are
      poorly understood. We recently identified a post germinal center tolerance
      checkpoint, where receptor editing is re-induced to extinguish autoreactivity
      that is generated by somatic hypermutation. Re-induction of the recombinase genes
      RAG1 and RAG2 in antigen-activated B cells requires antigen to engage the B cell
      receptor and IL-7 to signal through the IL-7 receptor. We demonstrate that this
      process requires IL-6 to upregulate IL-7 receptor expression on post germinal
      center B cells. Diminishing IL-6 by blocking antibody or haplo-insufficiency
      leads to reduced expression of the IL-7 receptor and RAG and increased titers of
      anti-DNA antibodies following immunization with a peptide mimetope of DNA. The
      dependence on IL-6 to initiate receptor editing is B cell intrinsic.
      Interestingly, estradiol decreases IL-6 expression thereby increasing the anti
      DNA response. Our data reveal a novel regulatory cascade to control post germinal
      center B cell autoreactivity.

PMID- 22154466
TI  - Maternal exposure to 17-alpha-ethinylestradiol alters embryonic development of
      GnRH-1 neurons in mouse.
AB  - To evaluate the potentially disrupting effects of environmental estrogens on
      neuroendocrine networks controlling reproduction, we studied the impact of the
      pharmaceutical product 17-alpha-ethinylestradiol (EE2) on gonadotropin-releasing
      hormone (GnRH-1) neuron development in mouse embryo. Pregnant mice were treated
      per os with EE2 at 0.01, 0.1 or 1 MUg/kg/day, between embryonic days 10.5 (E10.5)
      and E13.5, a period during which GnRH-1 neurons are generated and start their
      intra-nasal migration. Embryos at E13.5 were examined and processed for GnRH-1
      immunohistochemistry. Immunopositive neurons were counted all along their
      migratory path. A short oral administration of environmentally relevant doses of
      EE2 to pregnant mice had a significant impact on whole embryo development,
      leading to a limited but significant growth retardation. The total number of GnRH
      1 neurons was statistically significantly increased in a dose-dependent manner.
      The repartition of GnRH-1 neurons along their migratory path was not affected by
      EE2 treatment. These results suggest an impact of environmental EE2
      concentrations on embryonic GnRH-1 development through a modulation of
      neurogenesis and/or apoptosis.

PMID- 22154468
TI  - Drought tolerance through biotechnology: improving translation from the
      laboratory to farmers' fields.
AB  - Water availability is a significant constraint to crop production, and increasing
      drought tolerance of crops is one step to gaining greater yield stability.
      Excellent progress has been made using models to identify pathways and genes that
      can be manipulated through biotechnology to improve drought tolerance. A current
      focus is on translation of results from models in controlled environments to
      crops in the field. Field testing to demonstrate improved yields under water
      limiting conditions is challenging and expensive. More extensive phenotyping of
      transgenic lines in the greenhouse may contribute to improved predictions about
      field performance. It is possible that multiple mechanisms of drought tolerance
      may be needed to provide benefit across the diversity of water stress
      environments relevant to economic yield.

PMID- 22154467
TI  - Characterizing microbial communities through space and time.
AB  - Until recently, the study of microbial diversity has mainly been limited to
      descriptive approaches, rather than predictive model-based analyses. The
      development of advanced analytical tools and decreasing cost of high-throughput
      multi-omics technologies has made the later approach more feasible. However,
      consensus is lacking as to which spatial and temporal scales best facilitate
      understanding of the role of microbial diversity in determining both public and
      environmental health. Here, we review the potential for combining these new
      technologies with both traditional and nascent spatio-temporal analysis methods.
      The fusion of proper spatio-temporal sampling, combined with modern multi-omics
      and computational tools, will provide insight into the tracking, development and
      manipulation of microbial communities.

PMID- 22154469
TI  - Optical trapping for analytical biotechnology.
AB  - We describe the exciting advances of using optical trapping in the field of
      analytical biotechnology. This technique has opened up opportunities to
      manipulate biological particles at the single cell or even at subcellular levels
      which has allowed an insight into the physical and chemical mechanisms of many
      biological processes. The ability of this technique to manipulate microparticles
      and measure pico-Newton forces has found several applications such as
      understanding the dynamics of biological macromolecules, cell-cell interactions
      and the micro-rheology of both cells and fluids. Furthermore we may probe and
      analyse the biological world when combining trapping with analytical techniques
      such as Raman spectroscopy and imaging.

PMID- 22154470
TI  - Next generation sequencing and bioinformatic bottlenecks: the current state of
      metagenomic data analysis.
AB  - The recent technological advances in next generation sequencing have brought the
      field closer to the goal of reconstructing all genomes within a community by
      presenting high throughput sequencing at much lower costs. While these next
      generation sequencing technologies have allowed a massive increase in available
      raw sequence data, there are a number of new informatics challenges and
      difficulties that must be addressed to improve the current state, and fulfill the
      promise of, metagenomics.

PMID- 22154471
TI  - Single cell genome sequencing.
AB  - Whole genome amplification and next-generation sequencing of single cells have
      become a powerful approach for studying uncultivated microorganisms that
      represent 90-99% of all environmental microbes. Single cell sequencing enables
      not only the identification of microbes but also linking of functions to species,
      a feat not achievable by metagenomic techniques. Moreover, it allows the analysis
      of low abundance species that may be missed in community-based analyses. It has
      also proved very useful in complementing metagenomics in the assembly and binning
      of single genomes. With the advent of drastically cheaper and higher throughput
      sequencing technologies, it is expected that single cell sequencing will become a
      standard tool in studying the genome and transcriptome of microbial communities.

PMID- 22154472
TI  - Cesare Lombroso: Methodological ambiguities and brilliant intuitions.
AB  - This paper on Cesare Lombroso aims to assess his contribution to the
      criminological sciences. Although much praised worldwide, Lombroso was also the
      target of scathing criticism and unmitigated condemnation. Examination of
      Lombroso's method of data collection and analysis reveals his weakness. Indeed,
      his approach was extremely naive, simplistic and uncritical, aimed at irrefutably
      demonstrating the hypotheses that he championed, without exercising the
      methodological caution that was already beginning to characterize scientific
      research in his day. However, we must acknowledge that his biological theories of
      crime are undergoing new developments as a result of the recent success of
      biological psychiatry. On the other hand we should recognize that his work was
      not limited to his biological central theory; rather, it covered a range of cues
      and concepts, for the most part ignored, that demonstrate his interest in the
      economic, cultural and social factors that impact on crime. For these reasons,
      Lombroso appears to have anticipated many modern conceptions regarding delinquent
      behavior and criminal justice, such as those of restorative justice, the so
      called "situational" theories of criminal behavior and white collar crime.

PMID- 22154473
TI  - Global change ecotoxicology: Identification of early life history bottlenecks in
      marine invertebrates, variable species responses and variable experimental
      approaches.
AB  - Climate change is a threat to marine biota because increased atmospheric CO2 is
      causing ocean warming, acidification, hypercapnia and decreased carbonate
      saturation. These stressors have toxic effects on invertebrate development. The
      persistence and success of populations requires all ontogenetic stages be
      completed successfully and, due to their sensitivity to environmental stressors,
      developmental stages may be a population bottleneck in a changing ocean. Global
      change ecotoxicology is being used to identify the marine invertebrate
      developmental stages vulnerable to climate change. This overview of research, and
      the methodologies used, shows that most studies focus on acidification, with few
      studies on ocean warming, despite a long history of research on developmental
      thermotolerance. The interactive effects of stressors are poorly studied.
      Experimental approaches differ among studies. Fertilization in many species
      exhibits a broad tolerance to warming and/or acidification, although different
      methodologies confound inter-study comparisons. Early development is susceptible
      to warming and most calcifying larvae are sensitive to acidification/increased
      pCO2. In multistressor studies moderate warming diminishes the negative impact of
      acidification on calcification in some species. Development of non-calcifying
      larvae appears resilient to near-future ocean change. Although differences in
      species sensitivities to ocean change stressors undoubtedly reflect different
      tolerance levels, inconsistent handling of gametes, embryos and larvae probably
      influences different research outcomes. Due to the integrative 'developmental
      domino effect', life history responses will be influenced by the ontogenetic
      stage at which experimental incubations are initiated. Exposure to climate change
      stressors from early development (fertilization where possible) in multistressor
      experiments is needed to identify ontogenetic sensitivities and this will be
      facilitated by more consistent methodologies.

PMID- 22154474
TI  - mRNP quality control goes regulatory.
AB  - The accuracy of eukaryotic gene expression relies on efficient quality control
      (QC). Most steps in the gene expression pathway en route from transcription to
      translation are error-prone and QC systems have evolved to utilise many of these
      biochemical processes as checkpoints to monitor the production or function of
      mRNA-protein particles (mRNPs). Mechanistically, such evaluation of mRNP fitness
      is based on competition between the opposing activities of mRNP biogenesis and/or
      function and mRNP turnover. In fact, quite subtle alteration of any parameter can
      tip the balance between mRNP persistence and degradation and, therefore, QC
      checkpoints also comprise perfect opportunities for controlling cellular levels
      of individual or even entire families of transcripts. From this perspective, QC
      and gene regulation represent two outcomes of the same molecular process.

PMID- 22154475
TI  - Direct and indirect consequences of meiotic recombination: implications for
      genome evolution.
AB  - There is considerable variation within eukaryotic genomes in the local rate of
      crossing over. Why is this and what effect does it have on genome evolution? On
      the genome scale, it is known that by shuffling alleles, recombination increases
      the efficacy of selection. By contrast, the extent to which differences in the
      recombination rate modulate the efficacy of selection between genomic regions is
      unclear. Recombination also has direct consequences on the origin and fate of
      mutations: biased gene conversion and other forms of meiotic drive promote the
      fixation of mutations in a similar way to selection, and recombination itself may
      be mutagenic. Consideration of both the direct and indirect effects of
      recombination is necessary to understand why its rate is so variable and for
      correct interpretation of patterns of genome evolution.

PMID- 22154476
TI  - Pregnancy rate of Nelore females inseminated with male-sexed semen.
AB  - Pregnancy rates of Nelore females inseminated with male-sexed semen and
      conventional semen from the same bulls were evaluated. The females included 433
      heifers (2 years old) and 230 non-suckling cows, totaling 663 animals. Average
      body condition score was 3.5 (1-5 scale). Estrus was induced with prostaglandin
      F2alpha. The total pregnancy rate of females inseminated with male-sexed semen of
      bulls A, B and C was 38.8% (131/338) less (P<0.0001) than the total pregnancy
      rate observed for females inseminated with conventional semen from the same bulls
      (57.9% [188/325]). Pregnancy rates of non-suckling cows inseminated with male
      sexed semen was 43.3% (49/113), which was similar (P>=0.05) to the values found
      for heifers inseminated with male-sexed semen from the same bulls (36.4%
      [82/225]). The pregnancy rate of females inseminated with male-sexed semen was
      less compared with females inseminated with conventional semen. In addition,
      there was no significant difference in the pregnancy rate of heifers versus non
      suckling cows.

PMID- 22154477
TI  - Evaluation of the qualitative and quantitative effectiveness of three media of
      centrifugation (Maxifreeze, Cushion Fluid Equine, and PureSperm 100) in
      preparation of fresh or frozen-thawed brown bear spermatozoa.
AB  - Centrifugation is a crucial procedure in sperm cryopreservation protocols of
      brown bear (Ursus arctos), because the semen must be processed to increase sperm
      concentration and/or clean urine-contaminated samples. The efficacy of three
      media for centrifugation (Maxifreeze [IMV technologies, L'Aigle, France], Cushion
      Fluid Equine (Minitube, Tiefenbach, Germany), and PureSperm [Nidacon, Gothenburg,
      Sweden]) on the quality of bear spermatozoa was evaluated. In experiment one, two
      cushioned media used for protecting against mechanical stress during
      centrifugation were analyzed. In experiment two, a density gradient based on
      PureSperm was assessed in relation to the maximum retrieval and the quality of
      fresh spermatozoa, and the freezability of the spermatozoa selected in this
      density gradient was studied in experiment three. Finally, the selection of
      frozen-thawed sperm using PureSperm was analyzed in experiment four. Our results
      indicate that the use of dense isotonic cushion solutions (Maxifreeze, Cushion
      Fluid Equine) in centrifugation did not improve the quality of recovered
      spermatozoa compared with standard centrifugation. However, a density gradient
      prepared with PureSperm improved the quality of spermatozoa in fresh semen and
      frozen-thawed semen, but the spermatozoa selected from the fresh sample with this
      density gradient did not show a better resistance to freezing with this density
      gradient in comparison with the control sample.

PMID- 22154478
TI  - Antibacterial activity of optically transparent nanocomposite films based on
      chitosan or its derivatives and silver nanoparticles.
AB  - Colloidal silver nanoparticles (NPs) were prepared using the citrate and
      borohydride reduction methods and were then investigated as fillers in three
      matrices: unmodified chitosan, water-soluble chitosan and a N-alkyl chitosan
      derivative. The nanocomposites were used to prepare cast thin films (9-19 MUm
      thickness) and characterized for their optical and antimicrobial properties. The
      optical properties of the materials were adjusted either by varying the Ag NPs
      content in the films (0.5-3.9% w/w) or by using samples of Ag NPs with distinct
      particle size distributions. The antibacterial activity towards both Gram
      positive (Staphylococcus aureus) and Gram-negative bacteria (Klebsiella
      pneumoniae and Escherichia coli) was investigated for the various composites. For
      the unmodified chitosan nanocomposites, the bactericidal effect depended on their
      Ag content while such an effect was always observed for water-soluble chitosan
      and N-alkyl chitosan based materials. This research provides a basis for the
      evaluation of chitosan/silver composites in applications requiring flexible films
      with tuned optical properties and antimicrobial activity.

PMID- 22154480
TI  - An approach for mapping the vulnerability of European Union soils to antibiotic
      contamination.
AB  - Release of antibiotics into the environment through the agricultural reuse of
      animal manure is considered a cause of chronic environmental exposure that often
      leads to adverse ecotoxicological effects, as well as to the introduction of
      antibiotic-resistant bacteria into the environment. The vulnerability of soil to
      antibiotic contamination plays a major role in determining the extent of the
      contamination and the likelihood of the emergence of antibiotic resistance and
      the appearance of ecotoxicological effects. It depends on soil characteristics,
      which vary across Europe, and antibiotic characteristics, which vary across drug
      classes. Understanding how soil vulnerability varies geographically for different
      veterinary medicinal products would be very useful for resource allocation among
      surveillance programmes. This paper performs risk analysis of the EU region for
      12 antimicrobials using a spatial assessment performed in four steps. First,
      antibiotic release was estimated based on livestock density. Then exposure was
      estimated based on antimicrobial soil contamination. Third, consequences were
      modelled based on soil uses. Finally, risk was estimated by combining release,
      exposure and consequences using spatial multicriteria decision analysis. A final
      risk value for soil vulnerability was calculated for each antibiotic studied and
      displayed in chloropletic maps (ArcGIS 9.3). Furthermore, the Getis-Ord Gi
      statistic was used to identify clusters of areas at high risk for antibiotic soil
      contamination. Enrofloxacin was the highest-risk antibiotic in the European
      Union, followed by tetracyclines, tylosin and sulfodiazine. The highest risk
      values were found in Belgium, Ireland, Netherlands, Switzerland, Denmark, Germany
      and the UK. The results suggest that this methodology can be used successfully
      for evaluating the contamination potential of antibiotics over large areas with
      limited input data. This work is a preliminary step towards prioritising the use
      of veterinary medicinal products (VMPs), orientating monitoring studies and
      antimicrobial surveillance programmes, and informing sustainable decision-making
      for interventions designed to mitigate the risk of VMPs.

PMID- 22154479
TI  - Cumulative stress and maternal prenatal corticotropin-releasing hormone in an
      urban U.S. cohort.
AB  - BACKGROUND: To date, there have been conflicting reports of the association of
      psychosocial stressors with prenatal corticotropin-releasing hormone (CRH)
      levels. METHODS: We examined whether racial discrimination, community violence,
      interpersonal violence (IPV), negative life events, considered independently, and
      as a composite measure of cumulative stress, were associated with prenatal CRH
      levels in the Asthma Coalition on Community, Environment, and Social Stress
      (ACCESS) project, a multiethnic pre-birth cohort in urban Boston. Blood was
      collected between 20 and 37 weeks gestation (Mean=28.1, SD=4.6 weeks gestation).
      During pregnancy, women were administered the Conflict Tactics Scale survey to
      assess IPV, the Crisis in Family Systems-Revised survey to assess negative life
      events, the My Exposure to Violence survey to assess community violence, and the
      Experiences of Discrimination survey. A cumulative stress measure was derived
      from these instruments to characterize exposure to high levels of multiple
      stressors. RESULTS: None of the individual stressors or cumulative stress was
      associated with CRH in combined analyses including Whites (n=20), Blacks (n=46),
      and Hispanics (n=110). In separate analyses of Blacks and Hispanics, racial
      discrimination, community violence, and cumulative stress were associated with
      CRH in Blacks, but were not associated with CRH in Hispanics. CONCLUSIONS: Though
      these results require replication, they suggest that the effects of stress on
      prenatal CRH levels may be mediated by factors that differ between racial/ethnic
      groups. Further studies in larger samples are warranted to clarify whether
      associations of chronic stressors and prenatal CRH levels differ by
      race/ethnicity and to better understand underlying mechanisms.

PMID- 22154481
TI  - Study of the regional air quality south of Mexico City (Morelos state).
AB  - Results from the first study of the regional air quality in Morelos state
      (located south of Mexico City) are presented. Criteria pollutants concentrations
      were measured at several sites within Morelos in February and March of 2007 and
      2009; meteorological data was also collected along the state for the same time
      periods; additionally, a coupled meteorology-chemistry model (Mesoscale Climate
      Chemistry Model, MCCM) was used to gain understanding on the atmospheric
      processes occurring in the region. In general, concentrations of almost all the
      monitored pollutants (O(3), NO(x), CO, SO(2), PM) remained below the Mexican air
      quality standards during the campaign; however, relatively high concentrations of
      ozone (8-hour average concentrations above the 60 ppb level several times during
      the campaigns, i.e. exceeding the World Health Organization and the European
      Union maximum levels) were observed even at sites with very low reported local
      emissions. In fact, there is evidence that a large percentage of Morelos
      vegetation was probably exposed to unhealthy ozone levels (estimated AOT40 levels
      above the 3 ppm h critical limit). The MCCM qualitatively reproduced ozone daily
      variations in the sites with an urban component; though it consistently
      overestimated the ozone concentration in all the sites in Morelos. This is
      probably because the lack of an updated and detailed emission inventory for the
      state. The main wind patterns in the region corresponded to the mountain-valley
      system (downslope flows at night and during the first hours of the day, and
      upslope flows in the afternoon). At times, Morelos was affected by emissions from
      surrounding states (Distrito Federal or Puebla). The results are indicative of an
      efficient transport of ozone and its precursors at a regional level. They also
      suggest that the state is divided in two atmospheric basins by the Sierras de
      Tepoztlan, Texcal and Monte Negro.

PMID- 22154482
TI  - A methodological approach to evaluate arsenic speciation and bioaccumulation in
      different plant species from two highly polluted mining areas.
AB  - Arsenic accumulation and speciation in different plant species growing in two
      polluted sites were examined, in addition to arsenic transfer from soils to
      plants. The studied areas were two abandoned mercury mines in Northern Spain, La
      Soterrana and Los Rueldos. Plants accumulated extremely high amounts of arsenic
      in their tissues. Accumulation rates depend on both the grade of pollution of the
      site and on the plant species itself. Total arsenic concentrations varied
      depending on the part of the plant, with roots accumulating the most arsenic in
      all the studied plants (up to 1400 mg . kg(-1)). A suitable extraction method for
      arsenic speciation in the studied samples was developed and optimized using 0.3M
      orthophosphoric acid as the extracting agent in a graphite block digestion system
      at 90  degrees C for 1h. Extraction efficiencies were above 80% and speciation
      was not altered, since recoveries of the spiked arsenic species (As(III), As(V),
      DMA (dimethylarsonic acid) and MMA (monomethylarsonic acid)) were between 94 and
      102%. Speciation studies were performed on the parts of each plant species by
      means of HPLC-ICP-MS with the results indicating no significant differences in
      the speciation between parts of the plants. As(V) was always the predominant
      species, although a non-negligible amount of As(III) was found for all samples.
      Little amounts of MMA and DMA occurred in certain samples. Arsenic uptake by
      plants depends on the plant available arsenic fraction in soils, here considered
      as the sum of water-soluble and phosphate-extractable fractions. Although soils
      from La Soterrana were less polluted, arsenic bioavailability was much higher
      than in Los Rueldos. Soil-to-plant transfer factors, based on total and available
      arsenic in soils, were evaluated for the studied plants. Dryopteris filix-mas and
      Calluna vulgaris (L.) Hull, from La Soterrana and Los Rueldos respectively, were
      the plants with the highest abilities to extract arsenic from their corresponding
      soils.

PMID- 22154483
TI  - 'The placement was probably the tipping point' - the narratives of recently
      discontinued students.
AB  - Much has been written on student attrition from healthcare programmes and we know
      that it is often multifactorial. However in order to reduce attrition we need to
      gain a greater understanding of how multiple factors impact upon and compound one
      another to prompt a student to decide to leave. The purpose of this study was to
      explore healthcare students' experiences of university and the circumstances that
      initiated their decision to leave their programme. Sixteen students that had
      recently left healthcare programmes within the North West of England were
      interviewed by telephone, using a narrative prompt to facilitate them to tell
      their stories. All the students gave detailed narrative accounts that described
      their learning experiences, growing dissatisfaction and subsequent attrition. In
      the majority dissatisfaction and difficulties around clinical placements acted as
      a tipping point that precipitated departure.

PMID- 22154485
TI  - Expression of TNKS1 is correlated with pathologic grade and Wnt/beta-catenin
      pathway in human astrocytomas.
AB  - Astrocytoma is the most common neoplasm of the central nervous system, and its
      malignancy is closely related to activation of the Wnt/beta-catenin pathway.
      Accumulated evidence shows that tankyrase (TNKS) is necessary for the Wnt/beta
      catenin pathway, stabilizing beta-catenin, and that TNKS1, a major member of the
      TNKS family, is involved in a wide range of human cancers. However, the
      expression of TNKS1 and the molecular relationship between TNKS1 and beta-catenin
      in human astrocytomas is largely unknown. In the present study, we investigated
      the expression of TNKS1 in human astrocytomas using reverse transcription
      polymerase chain reaction, Western blot and immunohistochemistry. The mRNA and
      protein expression levels of TNKS1 in astrocytomas were significantly higher
      compared with the normal brain tissues. Significant association between TNKS1
      upregulation and pathological grade of astrocytomas was also confirmed. In
      addition, beta-catenin immunostaining of the sampled tissues revealed a highly
      similar change to TNKS1. This study provides additional evidence for the
      involvement of TNKS1 gene and the Wnt/beta-catenin signaling pathway in the
      genesis and progression of astrocytoma. TNKS1 may have a key role in
      astrocytomas.

PMID- 22154484
TI  - SREBPs: metabolic integrators in physiology and metabolism.
AB  - Recent advances have significantly increased our understanding of how sterol
      regulatory element binding proteins (SREBPs) are regulated at the transcriptional
      and post-transcriptional levels in response to cellular signaling. The
      phosphatidyl inositol-3-kinase (PI3K) and SREBP pathways intersect at multiple
      points, and recent insights demonstrate the importance of tight regulation of the
      PI3K pathway for regulating SREBPs in the adaptation to fluctuating dietary
      calorie load in the mammalian liver. In addition, genetic and genome-wide
      approaches highlight new functions for SREBPs in connecting lipid metabolism with
      other cellular processes where lipid pathway flux affects physiologic or
      pathophysiologic adaptation, such as cancer, steatosis, and innate immunity. This
      review focuses on recent advances and new roles for mammalian SREBPs in
      physiology and metabolism.

PMID- 22154486
TI  - Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for
      mesial temporal lobe sclerosis.
AB  - Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy
      (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who
      have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were
      collected prospectively from patients with nMRI who underwent temporal lobe
      surgery for TLE characterized by unilateral ictal temporal lobe seizure onset
      based on a scalp video electroencephalogram or invasive subdural electrode
      recordings. A total of 86 patients were followed for at least 24 months after
      surgery. Outcome was evaluated using the Engel classification. Seizure control
      was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed
      significant improvement (CL-II) and 19% (16/86) were deemed surgical failures.
      Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5
      7 Hz) were the most significant predictors of postoperative seizure control.
      Although hypometabolism on positron emission tomography scan and significant
      memory disparity (>2.5/8) were not significant prognosticators independently,
      cumulatively they were predictors for favorable outcome.

PMID- 22154487
TI  - [Metabolic syndrome in patients with schizophrenia independently from atypical
      antipsychotics intake].
AB  - BACKGROUND: The association between schizophrenia and the metabolic syndrome is
      frequent and well studied in the literature. The risk of induction of this
      syndrome by atypical antipsychotic drugs in patients with schizophrenia is well
      known. The aim of this study is to evaluate the association between schizophrenia
      and the metabolic syndrome independently from the risk of induction of this
      syndrome by atypical antipsychotic drugs. METHODS: A search was done via MedLine
      for articles written in English or in French, published between 1988 (date of
      establishment of the first definition of the metabolic syndrome) and December
      2010, using the following terms: "metabolic syndrome", "dyslipidemia", "glucose
      intolerance" or "diabetes" in association with "schizophrenia" or "psychosis".
      RESULTS: Evidence on the existence of a relationship between severe mental
      disorders such as schizophrenia and the metabolic syndrome exist before the
      introduction of the first antipsychotic drug in 1952. Other than atypical
      antipsychotic drugs, psychotropic drugs such as antidepressants and mood
      stabilizers, which can be frequently given to patients with schizophrenia, are
      also incriminated in the induction of some of the components of the metabolic
      syndrome. Patients suffering from schizophrenia present a tendency toward having
      an abdominal obesity, an excess of circulating cortisol as a consequence of this
      central obesity and a hepatic insulin resistance. Their reaction to continuous
      stress hyper activates the hypothalamo-pituitary-adrenal axis. Some genetic
      features are common to both schizophrenia and metabolic syndrome. Finally, the
      lifestyle of patients with schizophrenia is full of risk factors that can
      aggravate the metabolic syndrome such as sedentarism, smoking habits, low socio
      economic status, low adherence to medical care etc. CONCLUSION: The relationship
      between schizophrenia and the metabolic syndrome seems to contain, in the current
      medical literature, more than the simple fact related to the intake of atypical
      antipsychotic drugs.

PMID- 22154488
TI  - Use of pedometers to identify less active children and time spent in moderate to
      vigorous physical activity in the school setting.
AB  - OBJECTIVES: To examine in the context of a school day whether a pedometer,
      compared to an accelerometer, was an effective tool to identify children with low
      physical activity levels. Additionally, to characterise within the school day,
      patterns of variation in level and timing of activity of the most active and
      least active children. DESIGN: Observational study to compare two methods
      (accelerometer and pedometer) of identifying less active children and intensity
      of activity. METHOD: During school hours, for three consecutive days, children
      (n=47, aged 8-11 years) in two classes wore an accelerometer and sealed
      pedometer. Accelerometers were programmed to record at 15s epochs and the number
      of pedometer steps taken were recorded at the end of each school day. Patterns of
      activity by total accelerometer counts, and with cutoffs applied, were examined
      against time and the number of steps taken. RESULTS: Based on the accelerometer
      (>1500 counts/min), the majority (68%) of children spent more than 60 min in
      moderate to vigorous physical activity (MVPA) during the school day. Overall,
      time spent in MVPA was three times greater during break times compared to
      classroom time, with no apparent differences by class/age or gender. Total
      accelerometer counts and pedometer steps were correlated (r=0.60). One minute of
      MVPA was equivalent to 45 (95% CI 20 to 70) pedometer steps. CONCLUSION: The
      pedometer, a practical, relatively inexpensive tool, is suitable for the
      identification of less active children and has some utility to assess the
      relative intensity of activities in the context of a school day.

PMID- 22154489
TI  - Differences in wrist mechanics during the golf swing based on golf handicap.
AB  - OBJECTIVES: Variation in swing mechanics between golfers of different skill
      levels has been previously reported. To investigate if differences in three
      dimensional wrist kinematics and the angle of golf club descent between low and
      high handicap golfers. DESIGN: A descriptive laboratory study was performed with
      twenty-eight male golfers divided into two groups, low handicap golfers (handicap
      = 0-5, n = 15) and high handicap golfers (handicap >= 10, n = 13). METHODS:
      Bilateral peak three-dimensional wrist mechanics, bilateral wrist mechanics at
      ball contact (BC), peak angle of descent from the end of the backswing to ball
      contact, and the angle of descent when the forearm was parallel to the ground
      (DEC-PAR) were determined using an 8 camera motion capture system. Independent t
      tests were completed for each study variable (alpha = 0.05). Pearson correlation
      coefficients were determined between golf handicap and each of the study
      variables. RESULTS: The peak lead arm radial deviation (5.7 degrees, p = 0.008),
      lead arm radial deviation at ball contact (7.1 degrees, p = 0.001), and DEC-PAR
      (15.8 degrees, p = 0.002) were significantly greater in the high handicap group.
      CONCLUSION: In comparison with golfers with a low handicap, golfers with a high
      handicap have increased radial deviation during the golf swing and at ball
      contact.

PMID- 22154490
TI  - Self-induced seizures presumably by peri-orbital somatosensory self-stimulation:
      a report of two cases.
AB  - Self-induced seizures by somatosensory stimulation are rare. We describe two
      epileptic patients with self-induced seizures presumably by peri-orbital
      somatosensory stimulation. Two infants with severely delayed psychomotor
      development and poor visual acuity after acute subdural hemorrhage in early
      infancy had been diagnosed as having West syndrome. They evolutionally became to
      show serial self-induced seizures preceded by rubbing eye with finger in one case
      and touching right eyebrow with the back of left hand in the other case. Video
      electroencephalography (EEG) monitoring was useful to confirm self-induced
      seizure by peri-orbital self-stimulation. In patients with serial seizures
      preceded by peculiar behaviors, we need to consider the possibility of self
      induced seizures, even if they have a history of West syndrome and severe
      psychomotor retardation.

PMID- 22154491
TI  - Preparation and properties of the aldohexofuranose pentaacetates.
AB  - The preparation of one isomer of each of the 16 enantiomeric pairs of the
      aldohexofuranose pentaacetates is described together with (1)H and (13)C NMR
      data. Eight of the isomers have been obtained crystalline. Equilibrium values for
      the anomeric pairs have been determined.

PMID- 22154492
TI  - A convenient synthesis of glucose monomycolate.
AB  - An efficient synthesis of glucose monomycolate, an important lipidic antigen from
      Mycobacterium tuberculosis is described.

PMID- 22154493
TI  - Convenient strategies for the synthesis of 1,4-phenylene spaced sugars.
AB  - Two synthetic strategies have been developed for the synthesis of spaced sugars
      with lipophilic 1,4-phenylene core. A building block combining the usefulness of
      Weinreb amide functionality and modified Julia olefination reaction has been
      explored towards this objective. This building block offers complete flexibility
      in attaching any desired sugar derivative across phenylene spacer via C-C bond
      formation. The other strategy uses carbohydrate based building blocks for the
      synthesis of symmetrical as well as unsymmetrical 1,4-phenylene spaced sugars.
      This is the first report for the synthesis of 1,4-phenylene spaced sugars via C-C
      bond formation.

PMID- 22154494
TI  - Efficient and selective conversion of sucrose to 5-hydroxymethylfurfural promoted
      by ammonium halides under mild conditions.
AB  - The highly efficient and selective production of 5-hydroxymethylfurfural (HMF)
      from sucrose has been achieved in the presence of metal chlorides and ammonium
      halides under mild conditions. Notably, an 87% yield of HMF from sucrose was
      obtained with a catalyst system composed of CrCl(3) and NH(4)Br at 100 degrees C
      for 1.0 h in N,N-dimethylacetamide (DMAc) solvent. The effect of the reaction
      temperature and time was investigated in detail, and a possible mechanism for
      this catalytic process has been proposed. In addition, NH(4)Br is an effective
      promoter in the conversion of glucose and fructose to HMF.

PMID- 22154495
TI  - Diffusion of small molecules in a chitosan/water gel determined by proton
      localized NMR spectroscopy.
AB  - Proton localized NMR spectroscopy (MRS) has been applied to study the diffusion
      of three small molecules, caffeine, theophylline and caprolactam, in chitosan
      gels with different concentration of water. This technique allows the non
      destructive monitorization of diffusant concentration as a function of time and
      location. Concentration profiles were compared with theoretical curves based on
      solutions of Fick's diffusion equation for the best fitting, with the appropriate
      boundary conditions. The measured concentration profiles show a good agreement
      with the Fickian law. Values of the diffusion coefficients D ranging from 6.1*10(
      6) to 3.4*10(-6)cm(2)s(-1) depending on chitosan concentration and type of
      diffusant molecule were determined. In addition, measurements of diffusion
      coefficients at equilibrium conditions with proton pulsed field gradient NMR
      methods supported the observed Fickian behavior and showed values of D in
      excellent agreement with those determined by proton MRS. All these facts
      demonstrate that proton MRS is an appropriate method for investigating diffusion
      process in complex systems, such as polymer gels.

PMID- 22154496
TI  - Batch and column study: sorption of perfluorinated surfactants from water and
      cosolvent systems by Amberlite XAD resins.
AB  - Amberlite XAD resins have been employed to a great extent as the sorbent for
      removing or concentrating organic compounds from different matrices. We present
      for the first time a systematic study on the sorption of perfluorochemical (PFC)
      surfactants, an emerging class of environmental contaminants, by XAD-7HP
      (moderately polar) and XAD-2 (nonpolar). The results show that XAD-7HP can
      strongly sorb PFCs at circumneutral pH; the isotherm-determined linear sorption
      coefficient can reach 10(6)L/kg. On the other hand, the sorption coefficient for
      XAD-2 was two orders of magnitude lower than that for XAD-7HP. PFC sorption on
      XAD-7HP increased with an increase of the perfluorocarbon chain length of PFC and
      a decrease of the solution pH, indicating the importance of hydrophobic and
      electrostatic effects. The sorption coefficient for XAD-7HP reduced markedly with
      increasing fraction of the organic cosolvent (methanol) in the water-cosolvent
      mixture; however, the trend could not be predicted by a log-linear cosolvency
      model. Furthermore, the statistical analysis of column test results showed that
      after regeneration XAD-7HP can be used at least eight times without significant
      loss of performance. Finally, the experimental results imply that XAD-7HP
      sorption of shorter-chained PFCs (<=5 perfluorinated carbons) from water can be
      thermodynamically favorable.

PMID- 22154497
TI  - Contact line extraction and length measurements in model sediments and
      sedimentary rocks.
AB  - The mechanisms that govern the transport of colloids in the unsaturated zone of
      soils are still poorly understood, because of the complexity of processes that
      occur at pore scale. These mechanisms are of specific interest in quantifying
      water quality with respect to pathogen transport (e.g. Escherichia coli,
      Cryptosporidium) between the source (e.g. farms) and human users. Besides
      straining in pore throats and constrictions of smaller or equivalent size, the
      colloids can be retained at the interfaces between air, water, and grains.
      Theories competing to explain this mechanism claim that retention can be caused
      by adhesion at the air-water-interface (AWI) between sediment grains or by
      straining at the air-water-solid (AWS) contact line. Currently, there are no
      established methods for the estimation of pathogen retention in unsaturated media
      because of the intricate influence of AWI and AWS on transport and retention.
      What is known is that the geometric configuration and connectivity of the aqueous
      phase is an important factor in unsaturated transport. In this work we develop a
      computational method based on level set functions to identify and quantify the
      AWS contact line (in general the non-wetting-wetting-solid contact line) in any
      porous material. This is the first comprehensive report on contact line
      measurement for fluid configurations from both level-set method based fluid
      displacement simulation and imaged experiments. The method is applicable to any
      type of porous system, as long as the detailed pore scale geometry is available.
      We calculated the contact line length in model sediments (packs of spheres) as
      well as in real porous media, whose geometry is taken from high-resolution images
      of glass bead packs and sedimentary rocks. We observed a strong dependence of
      contact line length on the geometry of the sediment grains and the arrangement of
      the air and water phases. These measurements can help determine the relative
      contribution of the AWS line to pathogen retention.

PMID- 22154498
TI  - A national survey of UK obstetric units: the challenges of isolation.

PMID- 22154499
TI  - 20 years later: a second look on DF's motor behaviour.
AB  - The so-called action vs. perception model represents one of the currently
      dominating models addressing visual processing in primates. One of the crucial
      cornerstones of the action vs. perception model of visual processing is the
      dissociation of impaired perception versus intact visuomotor control in
      neurological patients with visual form agnosia (VFA). In fact, virtually all
      evidence related to VFA supporting the model was reported from only one patient:
      patient D.F. Through the last two decades D.F. became as important as only very
      few other exemplar cases in the neurosciences. However, a large corpus of
      experiments with this individual used methods that were insufficient to reveal
      less obvious impairments on a single subject level. We reanalysed the data of
      D.F. and identified basic visuomotor impairments that had been overlooked so far.
      Our reanalysis underlines the fact that the widespread and popular presentation
      of strong dissociations between distinct visual systems seems to be exaggerated.

PMID- 22154500
TI  - 'Frankie the Frog': the total transformation of a river basin as 'totalitarian'
      technology (Spain, 1946-1961).
AB  - After the Spanish Civil War (1936-1939), Francisco Franco's emphasis on dam
      building became so intense that it is still today associated with his dictatorial
      rule. Rather than being purely a personal obsession, however, this intensive
      period of reservoir construction was the result of the influential political role
      played by engineers from the early years of the regime. During the years 1946
      1961 some of these engineers undertook the 'total transformation' of the Noguera
      Ribagorzana river basin in the Catalonian Pyrenees. But this explicitly
      'totalitarian' project encountered important limitations posed both by competing
      state agencies and by the basin's geology. Analysing the efforts of these
      engineers allows for new understandings of the Francoist regime and of the place
      of science, technology, and the landscape within it.

PMID- 22154501
TI  - IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and
      microRNA-dependent gene regulation; comparative placentation; trophoblast
      differentiation; stem cells.
AB  - Workshops are an important part of the IFPA annual meeting as they allow for
      discussion of specialised topics. At IFPA meeting 2011 there were twelve themed
      workshops, five of which are summarized in this report. These workshops related
      to various aspects of placental biology: 1) immunology; 2) epigenetics; 3)
      comparative placentation; 4) trophoblast differentiation; 5) stem cells.

PMID- 22154502
TI  - Adverse pulmonary reactions associated with the use of monoclonal antibodies in
      cancer patients.
AB  - BACKGROUND: The incidence and clinical characteristics of adverse pulmonary
      reactions resulting from anticancer monoclonal antibody (mAbs) therapy have not
      been well described. We determined the incidence and clinical characteristics of
      adverse pulmonary reactions in patients treated with anticancer chemotherapy
      including mAbs. METHODS: A retrospective cohort study was performed including
      patients who were treated with a chemotherapeutic regimen that included
      rituximab, trastuzumab, cetuximab, or bevacizumab at Seoul National University
      Hospital between January 1, 2004 and December 31, 2008. Rates of adverse
      pulmonary reactions classified as non-infectious and infectious complications
      were compared with those among patients treated with comparable regimens without
      mAbs. RESULTS: In total, 1078 patients were included (418 for rituximab, 329 for
      trastuzumab, 122 for cetuximab, 209 for bevacizumab). Adverse pulmonary reactions
      were identified in 36 patients (3.5%) and the incidence differed among agents:
      cetuximab (9%), rituximab (5.3%), trastuzumab (0.6%), bevacizumab (0.5%).
      Infectious pulmonary complications occurred in 28 patients, and eight patients
      experienced non-infectious pulmonary complications, most commonly interstitial
      lung disease (6 patients). In a multivariate analysis, low serum albumin level
      was associated with the development of pulmonary complications. The incidence of
      overall adverse pulmonary reactions did not differ between the mAbs users and the
      1012 patients treated with comparable regimens other than mAbs (3.5% vs. 2.8%,
      P=0.53). CONCLUSIONS: Infectious and non-infectious adverse pulmonary reactions
      occur in patients with cancer who are administered a regimen including mAbs.
      Clinicians should be alert for the possibility of pulmonary adverse reactions,
      particularly among patients with low serum albumin levels.

PMID- 22154503
TI  - Applications of thermoelectric modules on heat flow detection.
AB  - This paper presents quantitative analysis and practical scenarios of
      implementation of the thermoelectric module for heat flow detection. Mathematical
      models of the thermoelectric effects are derived to describe the heat flow
      from/to the detected media. It is observed that the amount of the heat flow
      through the thermoelectric module proportionally induces the conduction heat
      owing to the temperature difference between the hot side and the cold side of the
      thermoelectric module. In turn, the Seebeck effect takes place in the
      thermoelectric module where the temperature difference is converted to the
      electric voltage. Hence, the heat flow from/to the detected media can be observed
      from both the amount and the polarity of the voltage across the thermoelectric
      module. Two experiments are demonstrated for viability of the proposed technique
      by the measurements of the heat flux through the building wall and thermal
      radiation from the outdoor environment during daytime.

PMID- 22154504
TI  - Socioeconomic differences in alcohol and drug use among Ghanaian adolescents.
AB  - Socioeconomic differences in experimental alcohol use, drunkenness, marijuana use
      and other drug uses among adolescents in Ghana was investigated using multiple
      socioeconomic indicators. A school-based cross-sectional survey of a
      representative sample of 12-18-year-olds (N=1195, response rate=89.7%) was
      conducted in Ghana in 2008. Logistic regression analysis was applied to model the
      associations between substance use and socioeconomic status. Use of marijuana and
      drugs was associated with lower material affluence while experimental alcohol use
      was associated with higher material affluence. Living in non-nuclear family was
      predictive of other drug uses and drunkenness. Other drug uses were associated
      with lower paternal education and occupation while drunkenness was associated
      with lower paternal education. Individual anticipated future social position
      measured by plans after graduation was the strongest predictor of experimental
      alcohol use, drunkenness, marijuana and other drug uses. Interventions are need
      to prevent adolescence substance use especially among those in danger of
      discontinuing schooling and those in less affluence families.

PMID- 22154505
TI  - Alexithymia and alcohol consumption: the mediating effects of drinking motives.
AB  - The association between alexithymia and alcohol consumption has been well
      documented. However, little research has investigated the mechanisms behind the
      association. In the present study, the relationship between alexithymia, drinking
      motives and alcohol consumption was examined in a group of social (non-problem)
      drinkers. In a cross-sectional study, 862 participants completed the Toronto
      Alexithymia Scale, Drinking Motives Questionnaire, and provided alcohol
      consumption information. Regression analyses revealed that alexithymia predicts
      alcohol consumption. Formal mediation analyses demonstrated that this
      relationship was fully mediated by social, enhancement and coping drinking
      motives, and partially mediated by conformity. Drinking motives may represent one
      mechanism to explain the association between alexithymia and alcohol consumption.

PMID- 22154506
TI  - Gender differences in physical and mental health outcomes among an aging cohort
      of individuals with a history of heroin dependence.
AB  - BACKGROUND: This paper examines the health status and functioning of an aging
      cohort of individuals with a history of heroin dependence with a focus on gender
      differences. METHOD: Study subjects were originally sampled from methadone
      maintenance clinics in California in the 1970s and completed follow-up interviews
      in 2005-09. Out of the original study sample (N=914), 343 participants (44.3%
      female) were interviewed (70.6% of those not deceased). Bivariate analyses
      examined gender differences in participants' overall health status and physical
      and mental health problems. Scores on SF-36 scales were compared with general
      population norms by gender and age, as well as between participants in the study
      sample who did and did not report past-year drug use. RESULTS: Average age of the
      study sample was 58.3 (SD=4.9) years for males and 55.0 (SD=4.1) years for
      females. There were no significant gender differences in past-year drug use (38%
      of sample) or injection drug use (19%). Women reported significantly more chronic
      health problems and psychological distress compared with men, and overall poorer
      health and functioning compared with general population norms. Men under 65 had
      poorer physical health and social functioning compared with population norms. Men
      in the study sample reporting past-year substance use had poorer physical
      functioning, but less bodily pain, than non-users, whereas women with past-year
      substance use had poorer mental health than other women. CONCLUSION: Individuals
      with a history of heroin dependence have poorer health and functioning than their
      counterparts in the general population. At a younger age, women reported poorer
      overall health status and more chronic health and mental health problems than
      men. Study findings may inform interventions for this population, particularly
      related to gender-specific treatment needs.

PMID- 22154507
TI  - Social cognitive predictors of smoking cessation intentions among smoker
      employees: the roles of anticipated regret and social norms.
AB  - The present study assessed the effects of anticipated regret, social norms, and
      related social cognitions on smoking cessation intentions among indoor employees
      in a pro-smoking culture. Overall, 93 daily smokers completed anonymous
      structured questionnaires assessing attitudinal and health beliefs about tobacco
      use, social norms, quitting self-efficacy, and anticipated regret. Past quit
      attempts and tobacco dependence were also measured. Hierarchical linear
      regression and mediation analyses showed that attitudes toward quitting, self
      efficacy and anticipated regret significantly predicted cessation intentions,
      over and above past quit attempts and tobacco dependence. Unlike in previous
      studies, tobacco dependence, descriptive norms and smoke-free policies did not
      directly influence quit intentions in our sample of smokers. Anticipated regret
      mediated the effects of attitudes and social norms on cessation intentions.

PMID- 22154508
TI  - The polymorphic prelude to Bateson-Dobzhansky-Muller incompatibilities.
AB  - Speciation research has largely assumed that the genetic causes of reproductive
      isolation are the work of fixed, divergent alleles that interact to cause genetic
      problems in hybrids: Bateson-Dobzhansky-Muller incompatibilities. However, many
      recent studies demonstrate substantial heritable polymorphism within species for
      hybrid incompatibility, herein called variable reproductive isolation (VRI). In
      this review, I outline the causes and importance of this general phenomenon. I
      also identify the new challenges of quantifying the relative contributions to
      reproductive isolation of fixed alleles versus polymorphisms, and the change in
      these contributions over the course of speciation. Explicit integration of VRI
      into speciation theory will help to quantify the relative roles of genetic drift
      and selection in speciation, but this synthesis requires substantial new
      contributions from both theory and empirical studies.

PMID- 22154509
TI  - A sensitive period for language in the visual cortex: distinct patterns of
      plasticity in congenitally versus late blind adults.
AB  - Recent evidence suggests that blindness enables visual circuits to contribute to
      language processing. We examined whether this dramatic functional plasticity has
      a sensitive period. BOLD fMRI signal was measured in congenitally blind, late
      blind (blindness onset 9-years-old or later) and sighted participants while they
      performed a sentence comprehension task. In a control condition, participants
      listened to backwards speech and made match/non-match to sample judgments. In
      both congenitally and late blind participants BOLD signal increased in bilateral
      foveal-pericalcarine cortex during response preparation, irrespective of whether
      the stimulus was a sentence or backwards speech. However, left occipital areas
      (pericalcarine, extrastriate, fusiform and lateral) responded more to sentences
      than backwards speech only in congenitally blind people. We conclude that age of
      blindness onset constrains the non-visual functions of occipital cortex: while
      plasticity is present in both congenitally and late blind individuals,
      recruitment of visual circuits for language depends on blindness during
      childhood.

PMID- 22154510
TI  - An ex vivo biomechanical comparison of a novel vertebral compression fracture
      treatment system to kyphoplasty.
AB  - BACKGROUND: Vertebral compression fracture repair aims to relieve pain and
      improve function by restoring vertebral structure and biomechanics, but is still
      associated with risks arising from polymethylmethacrylate cement extravasation.
      The Kiva(r) Vertebral Compression Fracture Treatment System, a stacked coil
      implant made of polyetheretherketone and delivered over a guide-wire, is a novel
      device designed to provide height restoration and mechanical stabilization, while
      improving cement containment and minimizing disruption of cancellous bone. The
      objective of this study was to determine whether the Kiva system is as effective
      as balloon kyphoplasty at restoring mechanical properties in osteoporotic
      vertebral compression fractures. METHODS: Wedge fractures were created in the
      middle vertebra of fourteen osteoporotic three-vertebra spine segments and then
      repaired with either the Kiva or kyphoplasty procedure. Height, stiffness and
      displacement under compression of the spine segments were measured for four
      conditions: intact, fractured, augmented, and post-cyclic eccentric loading
      (50,000cycles, 200-500N, 30mm anterior lever arm). FINDINGS: No significant
      differences were seen between the two procedures for height restoration,
      stiffness at high or low loads, or displacement under compression. However, the
      Kiva System required an average of 66% less cement than kyphoplasty to achieve
      these outcomes (mean 2.6 (SD 0.4) mL v. mean 7.5 (SD 0.8) mL 0; P<0.01).
      Extravasations and excessive posterior cement flow were also significantly lower
      with Kiva (0/7 v. 4/7; P<.05). INTERPRETATION: Kiva exhibits similar
      biomechanical performance to balloon kyphoplasty, but may reduce the risk of
      extravasation through the containment mechanism of the implant design and by
      reducing cement volume.

PMID- 22154511
TI  - Role for Class I histone deacetylases in multidrug resistance.
AB  - Recent reports have showed that histone deacetylase (HDAC) inhibitor resulted in
      multidrug resistance (MDR) to other chemotherapeutic agents. However, the
      molecular mechanisms of Class I HDACs on MDR regulation are poorly understood. In
      this study, HDAC1 and HDAC2 acted as enhancers to intensify the
      chemosensitivities of anti-cancer drugs via reducing the expression levels of P
      gp, MRP1 and MRP2. Furthermore, the dissociation of HDAC1 and HDAC2 led to
      transcriptional regulation of P-gp expression via the recruitment of p300, PCAF
      and NF-Y to the P-gp promoter region, which subsequently increased the level of
      the active gene marker, hyperacetylated histone H3. In parallel, selective
      inhibition of HDAC1 and HDAC2 induced the recruitment of p300, PCAF, NF-Y via
      acetylation of Sp1. Thus, our findings showed HDAC1 and 2 regulated P-gp
      expression through dynamic changes in chromatin structure and transcription
      factor association within the promoter region.

PMID- 22154512
TI  - Transcriptional profiling identifies upregulated genes following induction of
      epithelial-mesenchymal transition in squamous carcinoma cells.
AB  - During the progression of head and neck squamous cell carcinoma (HNSCC), the
      induction of an epithelial-mesenchymal transition (EMT) program may play a
      critical role in the dissemination of cells from the primary tumor to distant
      metastatic foci. The process of EMT involves the activation of several important
      genes and pathways to help maintain survival and growth and evolve into highly
      invasive and metastatic variants. In this study, expression microarray analysis
      identified a set of 145 upregulated genes in EMT-like HNSCC cells. Some of the
      strongly upregulated transcripts include genes that are reportedly involved in
      invasion and metastasis, such as DOCK10, LOX, ROBO1 and SRGN. Importantly, the
      Tbx3 gene, a member of the T-box transcription factor, was strongly upregulated
      in SCC cells displaying an EMT-like phenotype compared to cells with an
      epitheloid, non-EMT behavior. Tbx3 was also found to be strongly upregulated at
      the protein and gene expression level in an experimental model of snail-induced
      EMT cells. In addition, siRNA-induced Tbx3 depletion modestly suppressed cell
      invasion while enhancing Tbx3-mediated resistance to anoikis. Our findings
      provide evidence that Tbx3 overexpression promotes SCC cell survival displaying
      an EMT phenotype. This set of newly identified genes that are modulated during
      EMT-like conversion may be important diagnostic biomarkers during the process of
      HNSCC progression.

PMID- 22154513
TI  - CpG-DNA suppresses poly(I:C)-induced TSLP production in human laryngeal arytenoid
      fibroblasts.
AB  - Thymic stromal lymphopoietin (TSLP) exerts a marked influence on the polarization
      of dendritic cells to drive T helper (Th) 2 cytokine production, and has been
      linked to allergic airway diseases. Although TSLP is produced by airway
      epithelium, TSLP production in laryngeal arytenoid fibroblasts remains largely
      unexplored. We examined the effect of Toll-like receptor (TLR) ligands and the
      cross-talk that occurs among different TLR ligands on TSLP production in
      arytenoid fibroblasts. Since mRNA of TLR 2, 3, 4, and 9 has been found to be
      expressed in arytenoid fibroblasts, we examined the effect on its production of
      TLR ligands. TSLP production by arytenoid fibroblasts was strongly induced in the
      presence of polyinosinic-polycytidylic acid (poly(I:C)), a ligand of TLR3. Its
      production was synergistically induced in the presence of IL-4, to a level more
      than 100 times higher than that observed in the absence of poly(I:C) or IL-4. We
      also revealed that B type DNA containing CpG motifs (CpG-DNA) coding for a TLR9
      ligand markedly suppressed both poly(I:C)-induced and poly(I:C)-plus-IL-4-induced
      TSLP production. B type CpG-DNA decreased the poly(I:C)-induced phosphorylation
      of c-Jun N-terminal kinase (JNK), and pre-incubation with SP600125 (inhibitor of
      JNK) reduced the poly(I:C)-induced TSLP-production. These results indicate that
      human arytenoid fibroblasts strongly induce TSLP production with stimulation by
      double-stranded RNA (dsRNA), which can be inhibited by CpG-DNA and participate in
      immune allergic responses.

PMID- 22154514
TI  - Serum levels of inflammation factors and cognitive performance in amnestic mild
      cognitive impairment: a Chinese clinical study.
AB  - Early diagnosis of Alzheimer's disease (AD) is important for initiating timely
      therapy to block or slow the rate of disease progression. This study was designed
      to investigate the potential of inflammation-related biomarkers in peripheral
      blood to accurately reflect AD onset and progression. Individuals (n=150) with
      amnestic mild cognitive impairment (aMCI) were divided into two subgroups (low-
      and high-risk) based on APOEepsilon4 allele carrier status, and administered a
      battery of neuropsychological tests and tested for serum levels of IL-6, IL-10,
      TNF-alpha, and IFN-gamma by using specific enzyme-linked immunosorbent assays.
      Results were compared with those from age-matched healthy controls (n=150). The
      levels of IL-6 were significantly higher in the aMCI group than in controls
      (P<0.01). When the aMCI group was stratified by APOEepsilon4 status, significant
      differences were found between the low- and high-risk groups and controls in the
      levels of IL-6 and IFN-gamma (P<0.01 and P=0.041, respectively). Moreover, the IL
      6 level in the low-risk aMCI group was higher than that in the high-risk aMCI
      group (P=0.028). A weak but significant negative correlation was found between IL
      6 and cognitive performance. Taken together, these findings indicate that IL-6,
      while not useful alone, has potential in combination with other biomarkers to
      support early diagnosis of aMCI due to its association with the progression of
      cognitive impairment.

PMID- 22154515
TI  - Cognitive-behavioral therapy for depression in patients with temporal lobe
      epilepsy: a pilot study.
AB  - Depression has a high prevalence among patients with temporal lobe epilepsy
      (TLE). A pilot study was carried out to evaluate group cognitive-behavioral
      therapy (CBT) as a treatment for depression in patients with TLE. Twenty-three
      outpatients with TLE and major depressive disorder, according to DSM-IV criteria,
      were enrolled and divided into two groups to receive 16 weekly sessions of CBT.
      The primary outcome measures were depression severity (assessed with the Beck
      Depression Inventory) and quality of life (measured with the Quality of Life in
      Epilepsy-31). Sixteen patients (70%) completed at least 80% of the sessions. From
      week 8, CBT had a significant positive effect on severity of depression that
      lasted until the end of treatment. A significant improvement in quality of life
      was also observed. CBT seems to be a useful intervention for treating depression
      and improving quality of life in patients with TLE.

PMID- 22154516
TI  - Evolutionary informatics: unifying knowledge about the diversity of life.
AB  - The accelerating growth of data and knowledge in evolutionary biology is
      indisputable. Despite this rapid progress, information remains scattered, poorly
      documented and in formats that impede discovery and integration. A grand
      challenge is the creation of a linked system of all evolutionary data,
      information and knowledge organized around Darwin's ever-growing Tree of Life.
      Such a system, accommodating topological disagreement where necessary, would
      consolidate taxon names, phenotypic and geographical distributional data across
      clades, and serve as an integrated community resource. The field of evolutionary
      informatics, reviewed here for the first time, has matured into a robust
      discipline that is developing the conceptual, infrastructure and community
      frameworks for meeting this grand challenge.

PMID- 22154517
TI  - RINGs hold the key to ubiquitin transfer.
AB  - Ubiquitylation, the covalent modification of proteins by the addition of
      ubiquitin, relies on a cascade of enzymes that culminates in an E3 ligase that
      promotes the transfer of ubiquitin from an E2 enzyme to the target protein. The
      most prevalent E3 ligases contain a type of zinc-finger domain called RING, and
      although an essential role for the RING domain in ubiquitin transfer is widely
      accepted, the molecular mechanism by which this is achieved remains uncertain. In
      this review, we highlight recent studies that have suggested that the RING domain
      modulates the stability of the E2-ubiquitin conjugate so that catalysis is
      promoted. We also review the role of RING dimerisation and emphasise the
      importance of studying RING domains in the context of the full-length protein.

PMID- 22154518
TI  - A microRNA guide for clinicians and basic scientists: background and experimental
      techniques.
AB  - MicroRNAs (miRNAs) are short non-coding RNA molecules that are approximately 22
      nucleotides in length. In the last 10 years, miRNA research and discovery has
      advanced at a rapid rate. This review provides a brief overview of the discovery
      and biology of miRNAs, and summarises some of the experimental techniques used
      for isolation, detection, target prediction, and regulation of miRNAs. We also
      outline experimental workflows for investigators new to the field, and discuss
      the diagnostic and therapeutic application of miRNAs.

PMID- 22154519
TI  - Pulmonary hypertension and isolated right heart failure complicating amiodarone
      induced hyperthyroidism.
AB  - Hyperthyroidism is a common side effect encountered in patients prescribed long
      term amiodarone therapy for cardiac arrhythmias. We previously studied 354
      patients prescribed amiodarone in whom the occurrence of hyperthyroidism was
      associated with major adverse cardiovascular events including heart failure,
      myocardial infarction, ventricular arrhythmias, stroke and even death [1]. We now
      present a case of amiodarone-induced hyperthyroidism complicated by isolated
      right heart failure and pulmonary hypertension that resolved with treatment of
      hyperthyroidism. Detailed quantitative echocardiography enables improved
      understanding of the haemodynamic mechanisms underlying the condition.

PMID- 22154521
TI  - Predicting the future: from implicit learning to consolidation.
AB  - Sequence learning can be differentiated according to phases (rapid and slower),
      modalities (perceptual and motor), and whether or not it is conscious (implicit
      and explicit). Implicit sequence learning occurs when information is acquired
      from an environment of complex stimuli without conscious access either to what
      was learned or to the fact that learning occurred. In everyday life, this
      learning mechanism is crucial for adapting to the environment and for predicting
      events unconsciously. Implicit sequence learning underlies not only motor, but
      also cognitive and social skills; it is therefore an important aspect of life
      from infancy to old age. Moreover, this kind of learning does not occur only
      during practice, in the so-called online periods, but also between practice
      periods, during the so-called offline periods. The process that occurs during the
      offline periods is referred to as consolidation, which denotes the stabilization
      of a memory trace after the initial acquisition; this can result in increased
      resistance to interference or even improvement in performance following an
      offline period. Understanding the multiple aspects and influencing factors of
      consolidation can help us to reveal the nature of memory and changes in brain
      plasticity. Our review focuses on how consolidation varies with factors such as
      awareness, the length of offline periods, the type of information to be learned,
      and the age of participants. We highlight that consolidation is not a single
      process; instead, there are multiple mechanisms in the offline period, which are
      differently influenced by these factors.

PMID- 22154520
TI  - The association between insulin-like growth factor-I and cardiac repolarization.
AB  - OBJECTIVE: Previous studies reported associations between insulin-like growth
      factor I (IGF-I) serum concentration and cardiac morbidity and mortality, but the
      association between IGF-I serum concentration and cardiac repolarization has not
      been investigated in a population-based study so far. Therefore, we analyzed the
      impact of IGF-I concentrations on QTc, QT and RR intervals in two population
      based studies, The Study of Health in Pomerania (SHIP) and the Rotterdam Study.
      DESIGN: 457 individuals from SHIP and 155 individuals from the Rotterdam Study
      older than 55 years and without cardiovascular diseases and a left ventricular
      hypertrophy were investigated. IGF-I was determined by automated two-site
      chemiluminescence immunoassays and electrocardiograms were recorded by an ACTA
      electrocardiograph at a sampling frequency of 500 Hz. The association of IGF-I
      with QTc, QT and RR intervals was investigated by multivariable linear regression
      analyses adjusted for age, gender, diabetes mellitus, myocardial infarction,
      hypertension, body mass index, serum potassium and calcium in both studies
      separately and in pooled analysis. RESULTS: There were no significant
      associations between log-transformed IGF-I and QTc interval in the single
      populations, whereas a significant inverse association was detectable in the
      pooled population (beta, -15.6; 95%-confidence interval, -25.7, -5.5). The QTc
      interval was significantly higher in the first tertile of IGF-I compared to the
      third tertile (beta, 5.4; 95%-confidence interval, 9.5-1.3) in the pooled
      analysis. CONCLUSION: The inverse association between IGF-I serum concentrations
      and QTc interval in our study is suggestive of a higher risk for cardiac
      arrhythmias and thus might provide additional evidence for increased
      cardiovascular mortality in subjects with low IGF-I secretion.

PMID- 22154522
TI  - [Mycobacterium massiliense bone infection].

PMID- 22154523
TI  - [Phenotypic detection of carbapenemase associated with extended-spectrum beta
      lactamase in Klebsiella pneumoniae].

PMID- 22154524
TI  - Evaluation of empirical antibiotherapy for acute community-acquired pneumonia
      prescribed in emergency departments.
AB  - OBJECTIVE: The authors assessed the management of community-acquired pneumonia
      (CAP) and empirical antibiotic prescription in a primary care center. METHOD: A
      retrospective study was made on medical charts of patients admitted to the
      emergency department for CAP. RESULTS: Seventy-six patients were included. Their
      mean age was 65years for a sex ratio of 1.81. Fever (83%) and cough (72%) were
      the most common symptoms. Chest X-ray was abnormal in 86%. The median CRP value
      was 138mg/L (58-235). The median Fine's score was 85.5 (60-127). Blood cultures
      were sterile for 82.5% of samples. Pneumococcal and legionella antigenuria were
      performed for 70% of patients, only one was positive for legionella.
      Antibiotherapy was prescribed to 18 patients before hospitalization. Amoxicillin
      clavulanic acid was the most frequently prescribed empirical treatment (48.5%),
      followed by ceftriaxone (15%). The therapeutic adequation index was calculated at
      a median of 1.7 by three investigators (0-3.7). Kendall's concordance coefficient
      for the three investigators was good at 0.86 (P<0.0001). Close to 39% of
      antibiotic prescription had a bad therapeutic adequation index more than three.
      DISCUSSION: Our clinical, radiological, and microbiological data was quite
      similar to reported data from teaching hospital series except for severity that
      seemed lower in primary care centers. The therapeutic adequation index is a
      useful tool to assess the adequacy of antibiotic prescription.

PMID- 22154525
TI  - Active chromatin and noncoding RNAs: an intimate relationship.
AB  - Eukaryotic genomes are packaged into chromatin, where diverse histone
      modifications can demarcate chromatin domains that facilitate or block gene
      expression. While silent chromatin has been associated with long noncoding RNAs
      (lncRNAs) for some time, new studies suggest that noncoding RNAs also modulate
      the active chromatin state. Divergent, antisense, and enhancer-like intergenic
      noncoding RNAs can either activate or repress gene expression by altering histone
      H3 lysine 4 methylation. An emerging class of enhancer-like lncRNAs may link
      chromosome structure to chromatin state and establish active chromatin domains.
      The confluence of several new technologies promises to rapidly expand this
      fascinating topic of investigation.

PMID- 22154526
TI  - An impressive case of complete traumatic maxillofacial degloving.
AB  - By definition, degloving is skin and subcutaneous tissue detachment, most often
      affecting the limbs and extremities and occasionally the scalp. Degloving
      generally stems from high-energy trauma, but can also be intentional, such as in
      the case of planned surgical access in the anterior region of the mandible in
      oral-maxillofacial surgery. This paper describes an extreme case of complete
      traumatic maxillofacial degloving that caused partial avulsion of the soft
      tissues and maxilla. This is an extremely rare condition that has not previously
      been described in the literature, as the patient survived despite the risk of
      imminent death. This case report addresses the decisions made regarding the
      prevention of necrosis and infection that guided the emergency care and
      subsequent elective steps.

PMID- 22154527
TI  - Focal epithelial hyperplasia (Heck's disease) in two Chinese females.
AB  - Focal epithelial hyperplasia, or Heck's disease, is a relatively rare virus
      induced benign disease. To the best of the authors' knowledge it has not been
      reported in an ethnic Chinese population. The authors report two cases of focal
      epithelial hyperplasia (FEH) in Chinese patients, which were clinically and
      histologically in accord with FEH. In particular, the lesions in one case were
      located on the gingival mucosa, which is rarely affected by FEH. DNA extracted
      from paraffin-embedded specimens from the two patients was tested for the
      presence of human papilloma virus followed by specific polymerase chain reaction
      testing for 16, 18, 13, and 32 subtypes in order to confirm the clinical
      diagnosis.

PMID- 22154528
TI  - Dendritic cells from X-linked hyper-IgM patients present impaired responses to
      Candida albicans and Paracoccidioides brasiliensis.
AB  - BACKGROUND: Patients with X-linked hyper-IgM syndrome (X-HIGM) due to CD40 ligand
      (CD40L) mutations are susceptible to fungal pathogens; however, the underlying
      susceptibility mechanisms remain poorly understood. OBJECTIVE: To determine
      whether monocyte-derived dendritic cells (DCs) from patients with X-HIGM exhibit
      normal responses to fungal pathogens. METHODS: DCs from patients and controls
      were evaluated for the expression of costimulatory (CD80 and CD86) and MHC class
      II molecules and for their ability to produce IL-12 and IL-10 in response to
      Candida albicans and Paracoccidioides brasiliensis. We also evaluated the ability
      of C albicans- and P brasiliensis-pulsed mature DCs to induce autologous T-cell
      proliferation, generation of T helper (T(H)) 17 cells, and production of IFN
      gamma, TGF-beta, IL-4, IL-5, and IL-17. RESULTS: Immature DCs from patients with
      X-HIGM showed reduced expression of CD80, CD86, and HLA-DR, which could be
      reversed by exogenous trimeric soluble CD40L. Most important, mature DCs from
      patients with X-HIGM differentiated by coculturing DCs with fungi secreted
      minimal amounts of IL-12 but substantial amounts of IL-10 compared with mature
      DCs from normal individuals. Coculture of mature DCs from X-HIGM patients with
      autologous T cells led to low IFN-gamma production, whereas IL-4 and IL-5
      production was increased. T-cell proliferation and IL-17 secretion were normal.
      Finally, in vitro incubation with soluble CD40L reversed the decreased IL-12
      production and the skewed T(H)2 pattern response. CONCLUSION: Absence of CD40L
      during monocyte/DC differentiation leads to functional DC abnormalities, which
      may contribute to the susceptibility to fungal infections in patients with X
      HIGM.

PMID- 22154529
TI  - Undernutrition, subsequent risk of mortality and civil war in Burundi.
AB  - The paper investigates the effect of child undernutrition on the risk of
      mortality in Burundi. Using anthropometric data from a longitudinal survey (1998
      2007) we find that undernourished children, measured by the height-for-age z
      scores (HAZ) in 1998 had a higher probability to die during subsequent years. In
      order to address the problem of omitted variables correlated with both
      nutritional status and the risk of mortality, we use the length of exposure to
      civil war prior to 1998 as a source of exogenous variation in a child's
      nutritional status. Children exposed to civil war in their area of residence have
      worse nutritional status. The results indicate that one year of exposure
      translates into a 0.15 decrease in the HAZ, resulting in a 10% increase in the
      probability to die. For boys, we find a 0.34 decrease in HAZ per year of
      exposure, resulting in 25% increase in the probability to die. For girls, the
      results are statistically not significant at the usual thresholds. We show the
      robustness of our results and we derive policy conclusion for a nutrition
      intervention in times of conflict.

PMID- 22154530
TI  - Estimation of sex from sternal measurements in a Western Australian population.
AB  - In Australia, particularly Western Australia, there is a relative paucity of
      contemporary population-specific morphometric standards for the estimation of sex
      from unknown skeletal remains. This is largely a historical artefact from
      lacking, or poorly documented, repositories of human skeletons available for
      study. However, medical scans, e.g. MSCT (multislice spiral computed tomography)
      are an ingenious and practical alternative source for contemporary data. To that
      end, this study is a comprehensive analysis of sternal sexual dimorphism in a
      sample of modern Western Australian (WA) individuals with a main purpose to
      develop a series of statistically robust standards for the estimation of sex. The
      sample comprises thoracic MSCT scans, with a mean of 0.9 millimeter (mm) slice
      thickness, on 187 non-pathological sterna. Following 3D volume rendering, 10
      anatomical landmarks were acquired using OsiriX((r)) (version 3.9) and a total of
      8 inter landmark linear measurements were calculated using Morph Db (an in-house
      developed database application). Measurements were analyzed using basic
      descriptive statistics and discriminant function analyses, with statistical
      analyses performed using SPSS 19.0. All measurements are sexually dimorphic and
      sex differences explain 9.8-47.4% of sample variance. The combined length of the
      manubrium and body, sternal body length, manubrium width, and corpus sterni width
      at first sternebra contribute significantly to sex discrimination and yield the
      smallest sex-biases. Cross-validated classification accuracies, i.e., univariate,
      stepwise and direct function, are 72.2-84.5%, with a sex bias of less than 5%. We
      conclude that the sternum is a reliable element for sex estimation among Western
      Australians.

PMID- 22154531
TI  - Improving intraperitoneal chemotherapeutic effect and preventing postsurgical
      adhesions simultaneously with biodegradable micelles.
AB  - The two major concerns after cytoreductive surgery of abdominal and pelvic
      malignancies are residual tumors and peritoneal adhesions, which are inevitable
      and have great impact on prognosis. Therefore, to improve the intraperitoneal
      chemotherapeutic effect and prevent postsurgical adhesions simultaneously after
      surgery, we developed a novel strategy that combines the controlled drug delivery
      system (CDDS) with an antiadhesion barrier. Biodegradable poly(ethylene glycol)
      poly(E-caprolactone)-poly(ethylene glycol) (PECE) copolymer formed micelles in
      water, which turned instantly into a nonflowing gel at body temperature as a
      result of micellar aggregation. Effectiveness of doxorubicin-loaded PECE micelles
      (Dox-M) in improving intraperitoneal chemotherapeutic effect and preventing
      adhesions was investigated. Subsequently, we established a novel mouse model for
      postsurgical residual tumors and peritoneal adhesions, in which Dox-M could
      improve intraperitoneal chemotherapeutic effect and prevent postsurgical
      peritoneal adhesions simultaneously. Thus, it is a promising strategy to combine
      the CDDS and barrier method to improve the intraperitoneal chemotherapeutic
      effect and prevent peritoneal adhesions simultaneously after surgery.

PMID- 22154532
TI  - Vitamin A deficiency aggravates iron deficiency by upregulating the expression of
      iron regulatory protein-2.
AB  - OBJECTIVE: The aim of this study was to investigate the mechanism between vitamin
      A deficiency and anemia. METHODS: In this study, we performed animal and in vitro
      experiments to investigate the effect of vitamin A deficiency on iron regulator
      protein-2 (IRP2). In animal experiments, four parallel groups of rats were fed a
      control diet, a diet completely deficient in vitamin A, a diet marginally
      deficiency in vitamin A, and a diet marginally deficient in iron and vitamin A,
      respectively, for 8 wk. In the in vitro experiments, the primary hepatocytes were
      acquired from the livers of vitamin A- and iron-depleted rats. Ferritin (Fn),
      transferrin receptor (TfR), and IRP2 mRNA were measured by semiquantitive reverse
      transcription polymerase chain reaction. RESULTS: As expected, a decrease in the
      serum retinol concentration and an imbalance of iron metabolism existed in the
      vitamin A-deficient rats. The IRP2 mRNA level of the rats in the test groups was
      approximately two times that of the control group, whereas the Fn mRNA level and
      the TfR mRNA level were downregulated and upregulated, respectively, by the
      vitamin A deficiency. In the in vitro experiments, all-trans-retinoic acid
      induced a decrease of the IRP2 mRNA level in hepatocytes, whereas the Fn, TfR,
      and IRP2 mRNA levels regulated by all-trans-retinoic acid were reversed by the
      vitamin A receptor blocker Ro41-5253. CONCLUSION: Taken together, our results
      indicate that vitamin A is involved in the regulation of IRP2, subsequently
      affecting iron metabolism gene expressions, such as Fn and TfR. Investigating the
      mechanistic connection between vitamin A and iron metabolism would be helpful to
      characterize the importance of this nutrient-nutrient interaction.

PMID- 22154533
TI  - Child proportional scaling: is 1/3=2/6=3/9=4/12?
AB  - The current experiments examined the role of scale factor in children's
      proportional reasoning. Experiment 1 used a choice task and Experiment 2 used a
      production task to examine the abilities of kindergartners through fourth-graders
      to match equivalent, visually depicted proportional relations. The findings of
      both experiments show that accuracy decreased as the scaling magnitude between
      the equivalent proportions increased. In addition, children's errors showed that
      the cost of scaling proportional relations is symmetrical for problems that
      involve scaling up and scaling down. These findings indicate that scaling has a
      cognitive cost that results in decreasing performance with increasing scaling
      magnitude. These scale factor effects are consistent with children's use of
      intuitive strategies to solve proportional reasoning problems that may be
      important in scaffolding more formal mathematical understanding of proportional
      relations.

PMID- 22154534
TI  - Speed discrimination in 6- and 10-month-old infants follows Weber's law.
AB  - The speed of a moving object is a critical variable that factors into actions
      such as crossing a street and catching a ball. However, it is not clear when the
      ability to discriminate between different speeds develops. Here, we investigated
      speed discrimination in 6- and 10-month-old infants using a habituation paradigm
      showing infants events of a ball rolling at different speeds. The 6-month-olds
      looked longer at novel speeds that differed by a 1:2 ratio than at the familiar
      ones but showed no difference in looking time to speeds that differed by a 2:3
      ratio. In contrast, the 10-month-olds succeeded at discriminating a 2:3 ratio.
      For both age groups, discrimination was modulated by the ratio between novel and
      familiar speeds, suggesting that speed discrimination is subject to Weber's law.
      These findings show striking parallels to previous results in infants'
      discrimination of duration, size, and number and suggest a shared system for
      processing different magnitudes.

PMID- 22154535
TI  - [Diffusion MRI in the study of hepatic lesions].
AB  - Diffusion weighted imaging (DWI) in magnetic resonance imaging (MRI) is currently
      an important tool for detecting and characterising hepatic lesions, as well as
      for monitoring and evaluating the response to the treatment of the tumour
      disease. The use of this technique is also being assessed for the study of
      diffuse liver disease. Among the additional advantages of DWI-MRI, is the absence
      of emission of ionising radiation and not having to use paramagnetic contrasts,
      which means it can be used in the study of patients with renal failure. Another
      advantage is the short duration of the diffusion sequence, which means that the
      examination time in abdominal MRI is scarcely increased. Therefore, it is
      important that the physician is aware of this diagnostic technique, since DWI is
      a sequence that should be routinely included in the liver MRI study protocol.

PMID- 22154536
TI  - Determination of farm workers' exposure to pesticides by hair analysis.
AB  - In the present work, a highly sensitive method based on solid phase
      microextraction and gas chromatography tandem (triple quadrupole) mass
      spectrometry was used to test hair samples for 50 pesticides including 39
      molecules from different chemical families currently used in agriculture and 11
      organochlorines. The population investigated was composed of 18 farm workers who
      provided hair samples repeatedly collected during the entire treatment period
      (from March to November 2009). Among the 62 hair samples that were collected, 33
      different target molecules were detected. The most frequently detected
      agricultural pesticides were Diflufenican and Pyrimethanil, two herbicides which
      were detected in 13 subjects. The concentration in volunteers' hair matched with
      agricultural activity and the highest concentration was observed for Cyprodinil
      (1161pg/mg), an anilinopyrimidine used as a fungicide. For organochlorines, p,p'
      DDE and gamma-HCH were the most frequently detected molecules as they were
      present in at least one of the hair samples provided by each of the 18
      volunteers. The highest concentrations detected for these chemicals reached
      21.0pg/mg for p,p'-DDE and 23.5pg/mg for gamma-HCH, but the highest concentration
      of organochlorine was observed for beta-endosulfan (105pg/mg). The results
      suggest that farm workers have a weak, though constant exposure to organochlorine
      pesticides, especially to p,p'-DDE and gamma-HCH, while exposure to currently
      used pesticides is strongly associated with occupation. Observations also suggest
      that spraying work would not necessarily be the only source of exposure to
      agricultural pesticides and that worker not directly involved in spraying can
      also be submitted to significant level of exposure.

PMID- 22154537
TI  - In-the-bag capsular tension ring and intraocular lens subluxation or dislocation:
      a series of 23 cases.
AB  - OBJECTIVE: To describe clinical and pathologic findings from cases of in-the-bag
      capsular tension ring (CTR) and intraocular lens (IOL) subluxation or
      dislocation. DESIGN: Retrospective case series with clinicopathologic
      correlation. PARTICIPANTS: Twenty-three explanted subluxated/dislocated capsular
      bags containing a CTR and an IOL explanted in Europe and submitted in fixative to
      the Berlin Eye Research Institute. METHODS: Standard gross and light microscopy
      of specimens, complete histopathologic analyses of selected specimens done at the
      University of Utah, as well as questionnaire sent to explanting surgeons, and
      patient chart review, when available. MAIN OUTCOME MEASURES: Lens design,
      material, and abnormalities, capsular bag anomalies, patient demographic data,
      surgical dates, and presence or absence of known risk factors. RESULTS: Patients
      were aged 76.31 +/- 8.24 years at explantation, which was performed 81.5 +/- 32.2
      months after implantation. The IOLs in these cases were 3-piece hydrophobic
      acrylic (N = 11), 1-piece hydrophobic acrylic (n = 6), 3-piece silicone (n = 4),
      or 1-piece hydrophilic acrylic (n = 2) designs; all CTRs were made of poly(methyl
      methacrylate). Available information on associated ocular conditions included
      pseudoexfoliation (n = 17), glaucoma (n = 4), vitrectomy/retina surgery (n = 3),
      and trauma (n = 1). Complete histopathologic assessment in 3 specimens showed
      signs consistent with pseudoexfoliation, without available history related to
      this condition in one of the cases. Moderate/severe degrees of Soemmering's ring
      formation and capsulorhexis phimosis were observed or reported in 13 and 11
      specimens, respectively. Fourteen eyes were implanted and explanted by the same
      surgeon, with an interval of 92.7 +/- 23.4 months between the procedures. His
      rate of explantation because of subluxation/dislocation was 0.76% of the CTRs
      implanted during the time considered. CONCLUSIONS: Explantation because of
      postoperative subluxation or dislocation of CTR-IOL-capsular bag complexes
      occurred approximately 6.8 years after implantation in this series, providing
      further evidence that a fine line exists between zonular insufficiency that can
      be stabilized with the CTR alone and that requiring further support. Analyses of
      large series may help to define common factors associated with this complication,
      as well as surgical planning and employment of various endocapsular support
      devices to enhance postoperative zonular stabilization.

PMID- 22154538
TI  - Ultra-high resolution optical coherence tomography for differentiation of ocular
      surface squamous neoplasia and pterygia.
AB  - OBJECTIVE: To assess the use of an ultra-high-resolution (UHR) optical coherence
      tomography (OCT) as an adjuvant diagnostic tool in distinguishing ocular surface
      squamous neoplasia (OSSN) and pterygia. DESIGN: Prospective case series.
      PARTICIPANTS: Thirty-four eyes of 34 patients with conjunctival lesions
      clinically suspicious for OSSN or pterygia. METHODS: All patients were
      photographed and then imaged with a custom-built UHR OCT device. Subsequently,
      each patient underwent excisional or incisional biopsy with histopathologic
      diagnosis. MAIN OUTCOME MEASURES: Comparison of preoperative UHR OCT images and
      the corresponding histopathologic specimen; comparison of epithelial thickness
      between the 2 groups as measured by UHR OCT. RESULTS: Preoperative UHR OCT images
      of OSSN demonstrated similarities to the histopathologic specimens. Both optical
      and pathologic specimens showed a thickened layer of epithelium, often with an
      abrupt transition from normal to neoplastic tissue. Likewise, preoperative UHR
      OCT images of patients with pterygia were well correlated with the
      histopathologic specimens. As opposed to OSSN, both UHR OCT and pathologic images
      of pterygia demonstrated a normal thin epithelium, with underlying thickening of
      the subepithelial mucosal layers. Differences in the measured epithelial
      thickness on UHR OCT between OSSN and pterygia were statistically significant,
      with an average epithelial thickness of 346 MUm (standard deviation [SD], 167) in
      OSSN patients and 101 MUm (SD, 22) in pterygium patients (P<0.001). By receiver
      operating characteristic curve, the sensitivity and specificity of UHR OCT for
      differentiating between OSSN and pterygia was found to be 94% and 100%,
      respectively, using a cutoff value of 142 MUm. CONCLUSIONS: Ultra-high-resolution
      OCT may show promise as a noninvasive diagnostic tool to evaluate ocular surface
      lesions. In addition to a statistically significant difference in epithelial
      thickness, a significant degree of morphologic correlation with the
      histopathologic results demonstrates its potential in evaluating ocular surface
      squamous neoplasia and pterygia.

PMID- 22154539
TI  - Hypertension and symptomatic hypokalemia in a patient with simultaneous
      unilateral stenoses of intrarenal arteries and mesangioproliferative
      glomerulonephritis.
AB  - We present the case of a young patient with hypertension and unprovoked
      symptomatic hypokalemia. His workup uncovered secondary aldosteronism, moderate
      proteinuria, and, quite unusually, concurrent chronic hepatitis B. Detailed
      investigations, including renal angiography, renal vein sampling, and kidney
      biopsy, showed unilateral renin hypersecretion due to intrarenal arterial
      stenoses and mesangioproliferative glomerulonephritis, presumed to be secondary
      to hepatitis B infection. Targeted pharmacotherapy reversed all clinical
      manifestations, normalizing blood pressure and serum potassium level and
      achieving full remission of proteinuria and loss of hepatitis B surface antigen
      (HBsAg) and hepatitis B e antigen (HBeAg), and a dramatic decrease in viral load.

PMID- 22154540
TI  - A family with hyponatremia and the nephrogenic syndrome of inappropriate
      antidiuresis.
AB  - Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked
      disorder caused by activating mutations in arginine vasopressin receptor 2
      (AVPR2), resulting in persistently concentrated urine. We report on a family
      affected by NSIAD with the known mutation R137C, an arginine to cysteine
      substitution at amino acid 137. The spectrum of symptoms varied markedly and
      ranged from infrequent voiding to incidentally noted hyponatremia to recurrent
      admissions with hyponatremic seizures. There was evidence for physiologic
      compensatory mechanisms: most affected members intuitively compensated for the
      concentrated urine by curtailing their fluid intake. Before the genetic
      diagnosis, these members had recognized each other by their infrequent voiding,
      which especially suited one patient, a London cab driver. Interestingly, after
      water deprivation, urine osmolality was significantly lower in patients compared
      with unaffected members, suggesting desensitization of the downstream signaling
      pathway with persistent AVPR2 activation. Urine osmolality was as low as 241
      mOsm/kg (241 mmol/kg) in patients, which could obfuscate the diagnosis. The
      development of symptoms of hyponatremia was strikingly different in the 2 male
      patients: one patient was asymptomatic with a plasma sodium level of 120 mEq/L
      (120 mmol/L), whereas another experienced seizures with similar values.
      Investigations of such genetically defined patients show clues for the
      understanding of human physiology and inform diagnosis and clinical management.

PMID- 22154541
TI  - Acetaminophen may mediate oxidative stress and neurotoxicity in autism.

PMID- 22154542
TI  - Drugs of the future for Peyronie's disease.
AB  - With the increasing awareness of Peyronie's disease (PD), the interest in new
      concept medications to treat the disorder is escalating. Profibrogenic factors
      such as transforming growth factor (TGF)-beta1, endothelin (ET-1), connective
      tissue growth factor (CTGF), angiotensin (Ang) II and platelet derived growth
      factor (PDGF), all appear to be involved in the pathogenesis of PD. beta
      Thymosins, pirfenidone, nitric oxide (NO) donors, phosphodiesterase (PDE)-5
      inhibitors, matrix metalloproteinases (MMPs)/anti-tissue inhibitor of
      metalloproteinases (TIMP)-1 reduce collagen synthesis, while decorin,
      follistatin, and Smad 7 exert antifibrotic effects; all have been proposed for
      the treatment of PD. Alternative and/or novel approaches for the treatment of PD
      are needed in part because of the recognized multifactorial etiology of this
      complex disorder. A comprehensive approach for translating available experimental
      information into clinically effective drug trials for the treatment of PD is
      needed. We propose a multi-faceted approach for drug development to generate
      novel drug products for the treatment of PD.

PMID- 22154543
TI  - Linear mapping of numbers onto space requires attention.
AB  - Mapping of number onto space is fundamental to mathematics and measurement.
      Previous research suggests that while typical adults with mathematical schooling
      map numbers veridically onto a linear scale, pre-school children and adults
      without formal mathematics training, as well as individuals with dyscalculia,
      show strong compressive, logarithmic-like non-linearities when mapping both
      symbolic and non-symbolic numbers onto the numberline. Here we show that the use
      of the linear scale is dependent on attentional resources. We asked typical
      adults to position clouds of dots on a numberline of various lengths. In
      agreement with previous research, they did so veridically under normal
      conditions, but when asked to perform a concurrent attentionally-demanding
      conjunction task, the mapping followed a compressive, non-linear function. We
      model the non-linearity both by the commonly assumed logarithmic transform, and
      also with a Bayesian model of central tendency. These results suggest that
      veridical representation numerosity requires attentional mechanisms.

PMID- 22154544
TI  - Understanding recovery from object substitution masking.
AB  - When we look at a scene, we are conscious of only a small fraction of the
      available visual information at any given point in time. This raises profound
      questions regarding how information is selected, when awareness occurs, and the
      nature of the mechanisms underlying these processes. One tool that may be used to
      probe these issues is object-substitution masking (OSM). In OSM, a sparse,
      temporally-trailing four dot mask can interfere with target perception, even
      though the target and mask have different contours and do not spatially overlap
      (Enns & Di Lollo, 1997). Here, we investigate the mechanisms underlying the
      recently discovered recovery from OSM observed with prolonged mask exposure
      (Goodhew, Visser, Lipp, & Dux, 2011). In three experiments, we demonstrate that
      recovery is unaffected by mask offset, and that prolonged physical exposure of
      the mask is not necessary for recovery. These findings confirm that recovery is
      not due to: (a) an offset transient impairing the visibility of other stimuli
      that are nearby in space and time, or (b) mask adaptation or temporal object
      individuation cues resulting from prolonged mask exposure. Instead, our results
      confirm recovery as a high-level visual-cognitive phenomenon, which is inherently
      tied to target-processing time. This reveals the prolonged iterative temporal
      dynamics of conscious object perception.

PMID- 22154545
TI  - Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8
      dependent and HR23B-independent.
AB  - INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy
      that is increasing in incidence. The caspase 8 inhibitor FLIP is an anti
      apoptotic protein over-expressed in several cancer types including MPM. The
      histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) is currently being
      evaluated in relapsed mesothelioma. We examined the roles of FLIP and caspase 8
      in regulating SAHA-induced apoptosis in MPM. METHODS: The mechanism of SAHA
      induced apoptosis was assessed in 7 MPM cell lines and in a multicellular
      spheroid model. SiRNA and overexpression approaches were used, and cell death was
      assessed by flow cytometry, Western blotting and clonogenic assays. RESULTS: RNAi
      mediated FLIP silencing resulted in caspase 8-dependent apoptosis in MPM cell
      line models. SAHA potently down-regulated FLIP protein expression in all 7 MPM
      cell lines and in a multicellular spheroid model of MPM. In 6/7 MPM cell lines,
      SAHA treatment resulted in significant levels of apoptosis induction. Moreover,
      this apoptosis was caspase 8-dependent in all six sensitive cell lines. SAHA
      induced apoptosis was also inhibited by stable FLIP overexpression. In contrast,
      down-regulation of HR23B, a candidate predictive biomarker for HDAC inhibitors,
      significantly inhibited SAHA-induced apoptosis in only 1/6 SAHA-sensitive MPM
      cell lines. Analysis of MPM patient samples demonstrated significant inter
      patient variations in FLIP and caspase 8 expressions. In addition, SAHA enhanced
      cisplatin-induced apoptosis in a FLIP-dependent manner. CONCLUSIONS: These
      results indicate that FLIP is a major target for SAHA in MPM and identifies FLIP,
      caspase 8 and associated signalling molecules as candidate biomarkers for SAHA in
      this disease.

PMID- 22154546
TI  - Induction of an anti-inflammatory human monocyte subtype is a unique property of
      glucocorticoids, but can be modified by IL-6 and IL-10.
AB  - Glucocorticoids (GC) are the most widely used immunosuppressive agents in
      clinical medicine. Recently we showed that GC enhance survival of human monocytes
      and induce a specific anti-inflammatory monocyte subtype which actively induces
      resolution of inflammation. We now investigated if cytokines IL-4, IL-6 and IL
      10, which, like GC, have mostly anti-inflammatory effects on macrophages, would
      have GC-like effects also on monocytes. Human monocytes were stimulated with
      either cytokine, GC or combination thereof, and resulting effects on apoptosis,
      adherence, migration, phagocytosis, ROS production and cell surface phenotype
      were determined. We found that IL-4, IL-6, and IL-10 had either less or different
      effects on various anti-inflammatory functions of monocytes compared to GC. As
      such, IL-4 and IL-6 alone did not delay apoptosis while IL-10 even enhanced it.
      However, IL-6 or IL-10 increased GC-mediated protection from apoptosis when
      applied together with GC. Thus, the potential of GC to induce anti-inflammatory
      human monocytes is unique and not mimicked by the investigated cytokines.
      However, IL-6 and IL-10 amplify GC-induced anti-inflammatory and pro-resolution
      mechanisms by enhancing survival of GC-induced monocytes and thus sustaining
      their function. This combined effect of GC and cytokines could be important for
      the physiological switch from amplification towards resolution phase of
      inflammation.

PMID- 22154547
TI  - [Factors associated with health-related quality of life in the institutionalised
      elderly: differences between men and women].
AB  - AIM: To examine the relationship between co-morbidity, functional capacity, mood
      and perception of social support, and the physical and mental dimensions of the
      Health-Related Quality of Life and assess the differences between
      institutionalised elderly men and women without severe cognitive impairment in
      Cuenca, Spain. METHODS: A cross sectional, descriptive and multicentre study was
      conducted in 16 nursing homes. A representative sample of 281 elderly patients
      was randomly selected. MEASURES: demographic, clinic variables and standardised
      tools: SF12 health questionnaire, Mini-Mental State Examination, Barthel Index,
      Geriatric Depression Scale and Medical Outcomes Study Social Support Survey. Data
      analysis was performed using multiple lineal regression models for physical and
      mental dimension of SF12, differentiated for gender. RESULTS: The sample included
      55% elderly women with an mean age of 82.6 years, and 45% men with a mean age of
      81.2 years. Comorbidity was higher in women (1.96), but in the linear regression
      this was not associated with the physical dimension of HRQOL. We found an
      association with disability (beta=313), depressive symptoms (beta=-.164) and
      perceived social support (beta=158). The worst HRQOL in women was found in the
      mental dimension associated with depressive symptoms (beta= -.422) and in the low
      perceived social support (beta=154). CONCLUSIONS: Biological and functional
      factors were only associated with the physical dimension, while depression was
      associated with both dimensions (physical and psychological). The differential
      factor that could explain the lower HRQOL in institutionalised women could be
      explained by a more negative experience of the disability and loss of social
      support.

PMID- 22154548
TI  - [Effectiveness of pre-operative education in reducing anxiety in surgical
      patients].
AB  - OBJECTIVE: To evaluate the effectiveness of a structured pre-operative interview
      conducted by operating room nurses in order to reduce the pre-operative anxiety
      of patients, and to determine the profile of patients who can benefit from it.
      MATERIAL AND METHODS: A randomised double-blind and prospective trial was
      conducted on a sample of 335 patients scheduled for surgery in two regional
      hospitals in the Basque Region of Spain, Alto Deba Hospital and Mendaro Hospital.
      We compared the alternative of using a structured briefing (test group) with the
      current situation without any formal intervention (control group). The
      effectiveness of the procedure was determined using the STAI state anxiety self
      assessment questionnaire. The Chi-squared statistic was used to assess the
      differences in factors and the Student t-test for comparison of means in the
      continuous variables. RESULTS: The impact of the intervention on measures of
      state anxiety and trait anxiety was found to be not statistically significant,
      although the mean state anxiety state was slightly lower in the intervention
      group (18.96) than in the controls (20.03). Women undergoing surgery in the
      specialty of gynaecology showed the higher state anxiety compared with other
      specialties. As regards trait anxiety a higher ASA level is associated with
      higher anxiety. Furthermore, the consumption of psychotropic drugs is also
      related to a higher level of trait anxiety. CONCLUSION: The preoperative visit
      can be helpful when patients are selected according to specific characteristics:
      by type of anaesthesia, gender, or type of surgery. There may also be beneficial
      effects when preoperative education is tailored according to patient's anxiety
      risk. The time immediately before surgery may not be the best time for conducting
      the visit, as this may make the patients more anxious.

PMID- 22154549
TI  - Highly effective removal of floxed Blasticidin S resistance cassettes from
      Dictyostelium discoideum mutants by extrachromosomal expression of Cre.
AB  - The inactivation of proteins in cells is inevitable to study their physiological
      role in various cellular processes. In contrast to strategies to alter the amount
      of active proteins in cells, only a gene knockout guarantees complete removal of
      the protein of interest. For Dictyostelium discoideum cells, the gene replacement
      construct typically consists of a Blasticidin S resistance (Bsr) cassette flanked
      by fragments of the target gene to allow insertion by homologous recombination.
      More advanced knockout constructs additionally carry loxP sites on both sides of
      the Bsr cassettes for subsequent removal of the selection marker by transient
      expression of Cre recombinase, thus allowing generation of multiple knockouts
      using just a single selection marker. However, due to its design, the available
      neomycin selection-based Cre expression plasmid occasionally tends to integrate
      into the genome and also yield only a moderate number of transfectants in liquid
      media. In some cases, for instance in SCAR-null cells, it was not possible to
      remove the Bsr cassette without stable integration of the Cre expression vector
      into the genome. To circumvent these difficulties we designed the
      extrachromosomal Cre-recombinase expression vector pTX-NLS-Cre. We verified the
      greatly improved efficacy of this novel Cre-loxP approach by removal of the Bsr
      cassette in five different cell lines including the SCAR-null mutant. As a
      consequence, this vector will be a highly valuable means for the rapid generation
      of single or multiple mutants remaining sensitive to the most reliable selection
      markers Blasticidin S and neomycin.

PMID- 22154550
TI  - Skeletal muscle-specific variant of nascent polypeptide associated complex alpha
      (skNAC): implications for a specific role in mammalian myoblast differentiation.
AB  - NAC (nascent polypeptide associated complex) is a heterodimer consisting of an
      alpha and a beta subunit. skNAC (skeletal and heart muscle-specific form of
      alphaNAC) is a variant of alphaNAC, which is induced in muscle differentiation
      and regeneration. We show here that skNAC expression is regulated by p38 MAPK,
      which plays a crucial role in myogenesis. Furthermore, inhibition of skNAC
      expression in myoblasts via specific siRNAs might lead to disturbed incorporation
      of myosin heavy chain (MyHC) into sarcomeres, however, it has no inhibitory
      effect on absolute MyHC protein levels. Taken together, our data suggest that
      skNAC regulates specific aspects of myogenesis.

PMID- 22154551
TI  - Effects of serum-free storage on morphology, phenotype, and viability of ex vivo
      cultured human conjunctival epithelium.
AB  - The use of amniotic membrane (AM) represents one of the major developments in
      ocular surface reconstruction. However, in a study on patients with primary
      pterygium, transplantation of AM with ex vivo expanded human conjunctival
      epithelial cells (HCjE) promoted earlier epithelialization than AM alone. We
      previously showed that cultured human limbal epithelial cells maintain their
      morphology, phenotype, and viability for one week when stored at 23 degrees C.
      The current study investigates the feasibility of storing HCjE in HEPES-MEM and
      Optisol-GS at 23 degrees C for 4 and 7 days, respectively. The five experimental
      groups were analyzed by light microscopy, immunohistochemistry, transmission
      electron microscopy, and a viability assay. The ultrastructural integrity of
      cultured HCjE was well preserved following 4 days of storage, however, 7 days of
      storage resulted in some loss of cell-cell contacts and epithelial detachment
      from the amniotic membrane. The number of microvilli in cultured HCjE not
      subjected to storage was 2.03+/-0.38 microvilli/MUm. In comparison, after 4 and 7
      days of HEPES-MEM storage this number was 1.69+/-0.54 microvilli/MUm; P=0.98 and
      0.89+/-1.0 microvilli/MUm; P=0.28, respectively. After Optisol-GS storage for 4
      and 7 days, the mean number of microvilli was 1.07+/-1.0 microvilli/MUm; P=0.47
      and 0.07+/-0.07 microvilli/MUm; P=0.03, respectively. The number of cell layers
      in cultured HCjE not subjected to storage was 4.4+/-0.3 cell layers, as opposed
      to 4.0+/-0.9 cell layers; P=0.89 after 4 days of HEPES-MEM storage and 2.8+/-0.6
      cell layers; P=0.01 after 7 days of storage in HEPES-MEM. The number of cell
      layers after 4 and 7 days of storage in Optisol-GS was 3.7+/-0.2 cell layers;
      P=0.46 and 3.4+/-0.4 cell layers; P=0.18, respectively. The expression of markers
      for undifferentiated cells (DeltaNp63alpha, ABCG2 and p63), proliferating cells
      (Ki67 and PCNA), goblet cells (Ck7 and MUC5AC), stratified squamous epithelial
      cells (Ck4), and apoptotic cells (caspase-3) in cultured HCjE appeared to be
      unchanged after 4 and 7 days of HEPES-MEM and Optisol-GS storage. The percentage
      of viable cells in cultured HCjE not subjected to storage (91.4%+/-3.2%) was
      sustained after 4 and 7 days of storage in HEPES-MEM (94.1%+/-4.5%; P=0.99 and
      85.1%+/-13.7%; P=0.87, respectively) as well as after 4 and 7 days of storage in
      Optisol-GS (87.7%+/-15.2%; P=0.97 and 79.8%+/-15.7%; P=0.48, respectively). We
      conclude that cultured HCjE may be stored for at least 4 days in serum-free
      conditions at 23 degrees C while maintaining the phenotype and viability. HEPES
      MEM appears to be comparable to Optisol-GS for serum-free storage with
      preservation of the ultrastructure for at least 4 days.

PMID- 22154552
TI  - Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury
      in guinea pig.
AB  - Molecular hydrogen (H(2)) is an efficient antioxidant that can selectively reduce
      hydroxyl radicals and inhibit oxidative stress-induced injuries. We investigated
      the protective effects and mechanism of hydrogen-rich saline in a glutamate
      induced retinal injury model. Retinal excitotoxicity was induced in healthy
      guinea pigs by injecting glutamate into the vitreous cavity. After 30 min,
      hydrogen-rich saline was injected into the vitreous cavity, the peritoneal cavity
      or both. Seven days later, the retinal stress response was evaluated by examining
      the stress biomarkers, inducible nitric-oxide synthase (iNOS) and glucose
      regulated protein 78 (GRP78). The impaired glutamate uptake was assessed by the
      expression of the excitatory amino acid transporter 1(EAAT-1). The retinal
      histopathological changes were investigated, focusing on the thicknesses of the
      entire retina and its inner layer, the number of cells in the retinal ganglion
      cell layer (GCL) and the ultrastructure of the retinal ganglion cells (RGCs) and
      glial cells. Compared with the glutamate-induced injury group, the hydrogen-rich
      saline treatment reduced the loss of cells in the GCL and thinning of the retina
      and attenuated cellular morphological damage. These improvements were greatest in
      animals that received H(2) injections into both the vitreous and the peritoneal
      cavities. The hydrogen-rich saline also inhibited the expression of glial
      fibrillary acidic protein (GFAP) in Muller cells, CD11b in microglia, and iNOS
      and GRP78 in glial cells. Moreover, the hydrogen-rich saline increased the
      expression of EAAT-1. In conclusion, the administration of hydrogen-rich saline
      through the intravitreal or/and intraperitoneal routes could reduce the retinal
      excitotoxic injury and promote retinal recovery. This result likely occurs by
      inhibiting the activation of glial cells, decreasing the production of the iNOS
      and GRP78 and promoting glutamate clearance.

PMID- 22154553
TI  - Pure bipolar electro-coagulation on functional cortex in the treatment of
      epilepsy involving eloquent areas.
AB  - PURPOSE: Although resection of an epileptogenic region remains the main procedure
      of epilepsy surgery, epileptogenic areas in functionally critical cortex cannot
      be approached in that manner. Bipolar electro-coagulation on functional cortex
      (BCFC) was developed to treat such refractory seizures without causing
      unacceptable neurological deficits. Here we report the outcome of this therapy.
      METHODS: Fifteen patients who underwent pure BCFC without resection between 2002
      and 2008 were retrospectively reviewed with regard to seizure outcome,
      postoperative complications, and predictive factors. KEY FINDINGS: Seven patients
      developed hemiparesis after the operation but fully recovered within 1-6 months.
      One patient developed mild dysphasia, which was resolved within 12 months. All
      neurological deficits were temporary in the sense that they ultimately did not
      result in a deficit that would be noticed during a standard clinical examination.
      There were no subdural hemorrhage and infection. Engel class I outcome was
      achieved in two (13.3%) patients; class II, in six (40%); class III, in three
      (20%); and class IV, in four (26.7%). SIGNIFICANCE: The BCFC technique is only a
      palliative surgery, and cannot be applied for all epilepsies, however, this
      therapy proved to be effective when the epileptogenic foci are located in
      unresectable cortex. BCFC is safe and easy to use.

PMID- 22154554
TI  - Unverricht-Lundborg disease: homozygosity for a new splicing mutation in the
      cystatin B gene.
AB  - Unverricht-Lundborg disease is the most common form of progressive myoclonic
      epilepsy (PME). It is due to cystatin B gene (CSTB) mutations. Several mutations
      in CSTB gene have been published, but few in homozygosity. We describe a patient
      with a new splicing alteration. Mutation Gln22Gln leads to abnormal splicing and
      partial inclusion of intronic sequence. This is one of the few cases of
      homozygosity for a non-classic mutation and adds to mutational heterogeneity of
      CSTB.

PMID- 22154555
TI  - The complexity of non face-to-face work with patients affected by metastatic
      breast cancer and their carers. The 'hidden consultations' of the clinical nurse
      specialist.
AB  - INTRODUCTION: Survival rates in breast cancer have risen in the last 30 years.
      Almost one third of those diagnosed will go onto developing metastatic breast
      cancer which is becoming a long term condition in cancer care. In 2006 429,000
      new cases of breast cancer were recorded across Europe. In recent years treatment
      for metastatic breast cancer in the UK has moved to the ambulatory setting
      meaning non face-to-face contact, for example through telephone consultation, has
      become a vital method of management. METHOD: A prospective study conducted over a
      1-month period at a London Trust. Data was collected by two clinical nurse
      specialists on incoming calls using Excel and a bespoke interrelational
      structured query database. These data were then mined using standard data mining
      techniques. RESULTS: The study collected 28 days of data. 229 patient and carer
      telephone contacts were recorded across the Trust. Most calls were from patients
      (62.5%). Incoming calls resulted in the delivery of 1282 interventions, a mean of
      six interventions per call (range 1-8) and clustered into four areas: meeting
      information needs (29%), symptom management (26%), psychological/social issues
      (33%) and other issues (12%). The incoming telephone work accounted for 63 h
      which represented 30% of the total working time of the clinical nurse specialist.
      Calls primarily originated from patients who were in the follow-up phase (43% of
      calls), a group usually thought to prefer self management.

PMID- 22154556
TI  - The secret languages of coevolved symbioses: insights from the Euprymna scolopes
      Vibrio fischeri symbiosis.
AB  - Recent research on a wide variety of systems has demonstrated that animals
      generally coevolve with their microbial symbionts. Although such relationships
      are most often established anew each generation, the partners associate with
      fidelity, i.e., they form exclusive alliances within the context of rich
      communities of non-symbiotic environmental microbes. The mechanisms by which this
      exclusivity is achieved and maintained remain largely unknown. Studies of the
      model symbiosis between the Hawaiian squid Euprymna scolopes and the marine
      luminous bacterium Vibrio fischeri provide evidence that the interplay between
      evolutionarily conserved features of the innate immune system, most notably
      MAMP/PRR interactions, and a specific feature of this association, i.e.,
      luminescence, are critical for development and maintenance of this association.
      As such, in this partnership and perhaps others, symbiotic exclusivity is
      mediated by the synergism between a general animal-microbe 'language' and a
      'secret language' that is decipherable only by the specific partners involved.

PMID- 22154557
TI  - Prediction of drug efficacy for cancer treatment based on comparative analysis of
      chemosensitivity and gene expression data.
AB  - The NCI60 database is the largest available collection of compounds with measured
      anti-cancer activity. The strengths and limitations for using the NCI60 database
      as a source of new anti-cancer agents are explored and discussed in relation to
      previous studies. We selected a sub-set of 2333 compounds with reliable
      experimental half maximum growth inhibitions (GI(50)) values for 30 cell lines
      from the NCI60 data set and evaluated their growth inhibitory effect
      (chemosensitivity) with respect to tissue of origin. This was done by identifying
      natural clusters in the chemosensitivity data set and in a data set of expression
      profiles of 1901 genes for the corresponding tumor cell lines. Five clusters were
      identified based on the gene expression data using self-organizing maps (SOM),
      comprising leukemia, melanoma, ovarian and prostate, basal breast, and luminal
      breast cancer cells, respectively. The strong difference in gene expression
      between basal and luminal breast cancer cells was reflected clearly in the
      chemosensitivity data. Although most compounds in the data set were of low
      potency, high efficacy compounds that showed specificity with respect to tissue
      of origin could be found. Furthermore, eight potential topoisomerase II
      inhibitors were identified using a structural similarity search. Finally, a set
      of genes with expression profiles that were significantly correlated with anti
      cancer drug activity was identified. Our study demonstrates that the combined
      data sets, which provide comprehensive information on drug activity and gene
      expression profiles of tumor cell lines studied, are useful for identifying
      potential new active compounds.

PMID- 22154558
TI  - Structure-based redesign of an edema toxin inhibitor.
AB  - Edema factor (EF) toxin of Bacillus anthracis (NIAID category A), and several
      other toxins from NIAID category B Biodefense target bacteria are adenylyl
      cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to
      3',5'-cyclic adenosine monophosphate (cAMP). We previously identified compound 1
      (3-[(9-oxo-9H-fluorene-1-carbonyl)-amino]-benzoic acid), that inhibits EF
      activity in cultured mammalian cells, and reduces diarrhea caused by
      enterotoxigenic Escherichia coli (ETEC) at an oral dosage of 15MUg/mouse. Here,
      molecular docking was used to predict improvements in potency and solubility of
      new derivatives of compound 1 in inhibiting edema toxin (ET)-catalyzed
      stimulation of cyclic AMP production in murine monocyte-macrophage cells (RAW
      264.7). Structure-activity relationship (SAR) analysis of the bioassay results
      for 22 compounds indicated positions important for activity. Several derivatives
      demonstrated superior pharmacological properties compared to our initial lead
      compound, and are promising candidates to treat anthrax infections and diarrheal
      diseases induced by toxin-producing bacteria.

PMID- 22154559
TI  - Design, synthesis and the effect of 1,2,3-triazole sialylmimetic
      neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase.
AB  - This work describes the synthesis of a series of sialylmimetic neoglycoconjugates
      represented by 1,4-disubstituted 1,2,3-triazole-sialic acid derivatives
      containing galactose modified at either C-1 or C-6 positions, glucose or gulose
      at C-3 position, and by the amino acid derivative 1,2,3-triazole fused threonine
      3-O-galactose as potential TcTS inhibitors and anti-trypanosomal agents. This
      series was obtained by Cu(I)-catalysed azide-alkyne cycloaddition reaction
      ('click chemistry') between the azido-functionalized sugars 1-N(3)-Gal
      (commercial), 6-N(3)-Gal, 3-N(3)-Glc and 3-N(3)-Gul with the corresponding alkyne
      based 2-propynyl-sialic acid, as well as by click chemistry reaction between the
      amino acid N(3)-ThrOBn with 3-O-propynyl-GalOMe. The 1,2,3-triazole linked sialic
      acid-6-O-galactose and the sialic acid-galactopyranoside showed high Trypanosoma
      cruzitrans-sialidase (TcTS) inhibitory activity at 1.0mM (approx. 90%), whilst
      only the former displayed relevant trypanocidal activity (IC(50) 260MUM). These
      results highlight the 1,2,3-triazole linked sialic acid-6-O-galactose as a
      prototype for further design of new neoglycoconjugates against Chagas' disease.

PMID- 22154560
TI  - Conjugation of a 3-(1H-phenanthro[9,10-d]imidazol-2-yl)-1H-indole intercalator to
      a triplex oligonucleotide and to a three-way junction.
AB  - A new intercalating nucleic acid monomer M comprising a 4-(1-indole)-butane-1,2
      diol moiety was synthesized via a classical alkylation reaction of indole-3
      carboxaldehyde followed by a condensation reaction with phenanthrene-9,10-dione
      in the presence of ammonium acetate to form a phenanthroimidazole moiety linked
      to the indole ring. Insertion of the new intercalator as a bulge into a Triplex
      Forming Oligonucleotide resulted in good thermal stability of the corresponding
      Hoogsteen-type triplexes. Molecular modeling supports the possible intercalating
      ability of M. Hybridisation properties of DNA/DNA and RNA/DNA three-way junctions
      (TWJ) with M in the branching point were also evaluated by their thermal
      stability at pH 7. DNA/DNA TWJ showed increase in thermal stability compared to
      wild type oligonucleotides whereas this was not the case for RNA/DNA TWJ.

PMID- 22154561
TI  - Directed evolution to re-adapt a co-evolved network within an enzyme.
AB  - We have previously used targeted active-site saturation mutagenesis to identify a
      number of transketolase single mutants that improved activity towards either
      glycolaldehyde (GA), or the non-natural substrate propionaldehyde (PA). Here, all
      attempts to recombine the singles into double mutants led to unexpected losses of
      specific activity towards both substrates. A typical trade-off occurred between
      soluble expression levels and specific activity for all single mutants, but many
      double mutants decreased both properties more severely suggesting a critical loss
      of protein stability or native folding. Statistical coupling analysis (SCA) of a
      large multiple sequence alignment revealed a network of nine co-evolved residues
      that affected all but one double mutant. Such networks maintain important
      functional properties such as activity, specificity, folding, stability, and
      solubility and may be rapidly disrupted by introducing one or more non-naturally
      occurring mutations. To identify variants of this network that would accept and
      improve upon our best D469 mutants for activity towards PA, we created a library
      of random single, double and triple mutants across seven of the co-evolved
      residues, combining our D469 variants with only naturally occurring mutations at
      the remaining sites. A triple mutant cluster at D469, E498 and R520 was found to
      behave synergistically for the specific activity towards PA. Protein expression
      was severely reduced by E498D and improved by R520Q, yet variants containing both
      mutations led to improved specific activity and enzyme expression, but with loss
      of solubility and the formation of inclusion bodies. D469S and R520Q combined
      synergistically to improve k(cat) 20-fold for PA, more than for any previous
      transketolase mutant. R520Q also doubled the specific activity of the previously
      identified D469T to create our most active transketolase mutant to date. Our
      results show that recombining active-site mutants obtained by saturation
      mutagenesis can rapidly destabilise critical networks of co-evolved residues,
      whereas beneficial single mutants can be retained and improved upon by randomly
      recombining them with natural variants at other positions in the network.

PMID- 22154562
TI  - Deglycosylation of cellulosomal enzyme enhances cellulosome assembly in
      Saccharomyces cerevisiae.
AB  - We have estimated the effects of hyper-mannosylation of dockerin-type cellulase
      on cellulosome assembly by using Saccharomyces cerevisiae and 44 protein
      glycosylation mutants, because the heterologous protein displayed on yeast is
      assumed to be modified by yeast-specific hyper-mannosylation. First, we
      constructed the yeast strain CtminiCipA, which displays a heterologous
      scaffolding protein (miniCipA from Clostridium thermocellum) on its cell surface,
      and glycosylation mutants secreting a dockerin-type cellulase (Cel8Aenz
      Cel48Sdoc: a fusion protein of the catalytic domain of C. thermocellum Cel8A and
      the dockerin domain of C. thermocellum Cel48S). Next, minicellulosomes were
      assembled by mixing the CtminiCipA strain and the dockerin-type cellulase
      secreted by each glycosylation mutant. By using an endoglucanase assay and flow
      cytometric analysis, we showed that some glycosylation mutants enhanced
      cellulosome assembly; in particular, disruption of glycosylation genes located in
      the endoplasmic reticulum showed intense enhancement. These findings suggest that
      inhibition of the core complex or precursor formation in protein glycosylation
      enhances cellulosome assembly, meaning that absence of glycosylation is more
      important for cellulosome assembly than reducing the size of the glycochain.

PMID- 22154563
TI  - Conjugation of genetically engineered protein phosphatases to magnetic particles
      for okadaic acid detection.
AB  - This work presents the functional characterisation of a protein phosphatase 2A
      (PP2A) catalytic subunit obtained by genetic engineering and its conjugation to
      magnetic particles (MPs) via metal coordination chemistry for the subsequent
      development of assays for diarrheic lipophilic marine toxins. Colorimetric assays
      with free enzyme have allowed the determination of the best enzyme activity
      stabiliser, which is glycerol at 10%. They have also demonstrated that the
      recombinant enzyme can be as sensitive towards okadaic acid (OA) (LOD=2.3MUg/L)
      and dinophysistoxin-1 (DTX-1) (LOD=15.2MUg/L) as a commercial PP2A and, moreover,
      it has a higher operational stability, which makes possible to perform the
      protein phosphatase inhibition assay (PPIA) with a lower enzyme amount. Once
      conjugated to MPs, the PP2A catalytic subunit still retains its enzyme activity
      and it can also be inhibited by OA (LOD=30.1MUg/L).

PMID- 22154564
TI  - Hyperosmotic pressure on HEK 293 cells during the growth phase, but not the
      production phase, improves adenovirus production.
AB  - Hyperosmotic stress has been widely explored as a means of improving specific
      antibody productivity in mammalian cell cultures. In contrast, a decrease in cell
      specific productivity of adenovirus production has been reported in several
      studies in which virus production in HEK 293 cell cultures was conducted under
      hyperosmotic conditions. However, production of viral vectors and, in particular,
      adenoviral vectors is the result of two consecutive phases: the growth phase and
      the virus production phase. In this study, the singular and combined effects of
      osmolality on the phases of cell growth and virus production were evaluated in
      culture media with osmolalities ranging from 250 to 410mOsm. A two-factor, five
      level full factorial design was used to investigate the effect of osmotic stress
      on cell physiology, as determined through the characterization of cell growth,
      cell metabolism, cell viability, cell cycle, cell RNA and total protein content,
      and total virus yield/cell-specific virus productivity. Overall, the results show
      that the growth of cells under hyperosmotic conditions induced favorable
      physiological states for viral production, and the specific virus productivity
      was improved by more than 11-fold when the medium's osmolality was increased from
      250 to 410mOsm during the cell growth phase. Both hypo- and hyperosmotic stresses
      in the virus production phase reduced virus productivity by as much as a factor
      of six. Optimal virus productivity was achieved by growing cells in media with an
      osmolality of 370mOsm or greater, followed by a virus production phase at an
      osmolality of 290mOsm. Compared to standard culture and production conditions in
      isotonic media, the shift from high to low osmolality between the two phases
      resulted in a two- to three-fold increase in virus yields. This hyperosmotic
      pressure effect on virus productivity was reproduced in five different commercial
      serum-free media.

PMID- 22154565
TI  - Unraveling navigational strategies in migratory insects.
AB  - Long-distance migration is a strategy some animals use to survive a seasonally
      changing environment. To reach favorable grounds, migratory animals have evolved
      sophisticated navigational mechanisms that rely on a map and compasses. In
      migratory insects, the existence of a map sense (sense of position) remains
      poorly understood, but recent work has provided new insights into the mechanisms
      some compasses use for maintaining a constant bearing during long-distance
      navigation. The best-studied directional strategy relies on a time-compensated
      sun compass, used by diurnal insects, for which neural circuits have begun to be
      delineated. Yet, a growing body of evidence suggests that migratory insects may
      also rely on other compasses that use night sky cues or the Earth's magnetic
      field. Those mechanisms are ripe for exploration.

PMID- 22154567
TI  - Is it valid to measure suicidal ideation by depression rating scales?
AB  - OBJECTIVE: To date, most researchers rely on suicidal items of scales primarily
      designed to measure depression severity to capture suicidal ideation (SI). This
      study aims at investigating how well the suicide item of the clinician rated
      Hamilton Scale for Depression (HAM-D) and principal factors derived from this
      scale correlate with SI scores derived from a well validated measure of SI: the
      Beck's scale for SI (SSI). METHOD: 281 suicide attempters consecutively
      hospitalized between 2007 and 2009 were assessed by using the SSI, the HAM-D and
      the self-report Beck Depression Inventory (BDI). Principal Component Analysis
      (PCA) was computed to extract main factors. Correlations between these factors,
      BDI's and HAM-D's suicide items and the SSI scores were then computed. RESULTS:
      Three components were derived from the PCA. Factor 2 showed a major loading for
      the HAM-D suicide item. Both the HAM-D suicide item and Factor 2 positively
      correlated with the SSI total score (both p<0.00001). Moreover, the BDI suicide
      item highly correlated with the Factor 2 (p<0.001) and the SSI total score
      (p<0.00001). Finally, the HAM-D suicide item correlated significantly with the
      number of suicide attempts (p=0.0001) and the age at the first attempt (p=0.002).
      LIMITATIONS: Our sample was heterogeneous and future studies should refine the
      taxonomy of the suicidal behavior in specific sub-populations. The study design
      was cross-sectional and replication in a prospective study is needed. CONCLUSION:
      These findings suggest that the use of a single suicide item or a dimensional
      factor derived from a depression scale might be a valid approach to assess the
      suicidal ideations. Moreover, the results suggest that clinician rated scales as
      well as self-report questionnaires are equally valid to do so.

PMID- 22154566
TI  - Associations between suicide attempts and elevated bedtime salivary cortisol
      levels in bipolar disorder.
AB  - BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been
      reported in bipolar disorder and also in suicidal behavior, but few studies have
      examined the relationship between suicidal behaviors and the HPA axis function in
      bipolar disorder, attending to and minimizing confounding factors. We compare HPA
      axis activity in bipolar individuals with and without suicidal behavior and
      unaffected healthy controls through measurement of salivary cortisol. METHOD:
      Salivary cortisol was collected for three consecutive days in 29 controls, 80
      bipolar individuals without a history of suicide and 56 bipolar individuals with
      a past history of suicide. Clinical factors that affect salivary cortisol were
      also examined. RESULTS: A past history of suicide was associated with a 7.4%
      higher bedtime salivary cortisol level in bipolar individuals. There was no
      statistical difference between non-suicidal bipolar individuals and controls in
      bedtime salivary cortisol and awakening salivary cortisol was not different
      between the three groups. LIMITATIONS: The measure of salivary cortisol was a
      home based collection by the study subjects and the retrospective clinical data
      was primarily based on their historical account. CONCLUSIONS: Bipolar individuals
      with a past history of suicidal behavior exhibit hyperactivity in the HPA axis.
      This biological marker remains significant regardless of demographic factors,
      mood state, severity and course of illness. This finding in bipolar disorder is
      consistent with the evidence for altered HPA axis functioning in suicide and mood
      disorders and is associated with a clinical subgroup of bipolar patients at
      elevated risk for suicide based on their history, and in need of further
      attention and study.

PMID- 22154568
TI  - Physico-chemical, textural and structural characteristics of sous-vide cooked
      pork cheeks as affected by vacuum, cooking temperature, and cooking time.
AB  - This paper describes the influence of different factors on sous-vide cooked pork.
      Pork cheeks were cooked at different combinations of temperature (60 degrees C or
      80 degrees C), time (5 or 12h) and vacuum (vacuum or air packaged). Weight losses
      were lower and moisture content higher in samples cooked for a shorter time
      (P=0.054) and at a lower temperature (P<0.001). Samples cooked at 60 degrees C
      showed more lightness (L*) and redness (a*) (P<0.001). Lipid oxidation showed an
      interaction between cooking time and temperature (P=0.007), with higher TBARs
      values for samples cooked for 12h at 60 degrees C and lower for those cooked for
      12h at 80 degrees C. Samples cooked at 80 degrees C for 12h showed lower (P<0.05)
      values for most textural parameters than all the other types of samples. Vacuum
      packaging showed no influence on any of the studied variables. For the treatments
      evaluated, cooking temperature*time combination seems to be more important than
      vacuum packaging in the textural and colour parameters of pork cheeks.

PMID- 22154569
TI  - Use of computed tomography to study raw ham properties and predict salt content
      and distribution during dry-cured ham production.
AB  - Varying salt content in hams of equal brand is a major challenge for Norwegian
      dry-cured ham producers. This study was thus undertaken to test existing computed
      tomography (CT) calibration models for salt on entire hams, regarding
      predictability of salt content at different processing times including final ham
      and to study salt distribution during processing of dry-cured ham. Twenty-six
      hams were scanned by computed tomography (CT) 11 times during dry-curing for this
      purpose. However, previously established calibration models had to be adjusted as
      they overestimated salt in dry samples. Prediction of ultimate salt content was
      more accurate approaching the end of the dry-curing process (RMSEP=0.351-0.595%
      salt). Inclusion of remaining weight loss improved the prediction accuracy in un
      dried samples by approximately 0.1% NaCl. The prediction errors were sufficiently
      low to be of practical interest.

PMID- 22154570
TI  - Implications of Zostera noltii recolonization on Hydrobia ulvae population
      structure success.
AB  - Over 1990-1998, the Mondego estuary, Portugal, experienced profound modifications
      due to eutrophication, culminating in the disappearance and replacement of
      Zostera noltii by opportunistic macroalgae in the inner most disturbed areas. A
      decade after restoration measures implementation, Z. noltii started to gradually
      recolonize the inner parts, following 20 years of absence. This work explores the
      factors underlying successful Z. noltii recolonization and its subsequent
      implications on a mud snail Hydrobia ulvae population. During the macroalgal
      bloom, highest values in H. ulvae abundance, biomass and production were
      recorded, strongly declining afterwards. Three recovery attempts characterized
      the post-restoration phase, with considerably increases in H. ulvae abundance,
      biomass and production since Z. noltii reappearance. The seagrass provided long
      term protection and abundant food resources for reproductive adults, contrarily
      to the ephemeral macroalgae. Through time, large size individuals increased,
      becoming the population more stable, structured and similar to the one inhabiting
      the "original"Z. noltii meadows.

PMID- 22154571
TI  - Elevated cortisol modulates Hsp70 and Hsp90 gene expression and protein in sea
      bass head kidney and isolated leukocytes.
AB  - In fish, interactions between Hsps and cortisol are involved in stress modulated
      physiological processes including innate immune responses. Cortisol exerts a role
      in the regulation of Hsps synthesis. Fish head kidney is a lymphomieloid and
      endocrine organ releasing cortisol, and it is the central organ for immune
      endocrine interactions. In sea bass, cortisol intraperitoneal injection and in
      vitro treatment of head kidney cells show that inducible Hsp70 and Hsp90 are
      modulated by this hormone. However, an inverse relationship between mRNA
      expression (real-time PCR) and Hsp70 and Hsp90 protein levels (densitometric band
      analysis) was found. Time-course assays indicate a cortisol-mediated regulation.
      Furthermore, Hsp70 gene modulation appears to be more susceptible to the cortisol
      action and the mRNA was transcribed within 3h post-injection. The restoration of
      the homeostatic conditions was observed at a week p.i., when plasma cortisol
      baseline was reached. Although fish manipulation and injection exerted stressing
      effects as indicated by serological parameters, differences between cortisol
      treated specimens compared to untreated or sham fish are statistically
      significant. Similar results were found by examining in vitro total cells and
      isolated leukocytes from head kidney cultured for 3h with increasing cortisol
      concentration. Finally, MTT test and DNA fragmentation experiments showed that
      the apoptotic effect expected in cortisol-treated cells could be counteracted by
      high Hsp70 intracellular levels.

PMID- 22154573
TI  - Hormones, life-history, and phenotypic variation: opportunities in evolutionary
      avian endocrinology.
AB  - Life-histories provide a powerful, conceptual framework for integration of
      endocrinology, evolutionary biology and ecology. This has been a commonly
      articulated statement but here I show, in the context of avian reproduction, that
      true integration of ultimate and proximate approaches has been slow. We have only
      a rudimentary understanding of the physiological and hormonal basis of phenotypic
      variation in (a) reproductive traits that contribute most to individual variation
      in lifetime fitness in birds (e.g. laying date, clutch size, parental effort) and
      (b) trade-offs that link these traits or that link reproduction to other life
      stages (e.g. migration, molt). I suggest that some reasons for this relative lack
      of progress include (a) an increasingly reductionist and centralist (upstream)
      focus which is more and more removed from ecological/evolutionary context, and
      from peripheral (downstream) mechanisms that actually determine how phenotypes
      work (b) a long-standing male-bias in experimental studies, even though the key
      reproductive traits which contribute most to variation in fitness are female
      specific traits (e.g. onset of vitellogenesis, egg size or number). Endocrine
      systems provide strong candidate mechanisms for regulation of phenotypic
      variation in single traits, and two endocrine concepts capture the essence of
      life-history trade-offs: (a) hormonal 'pleiotropy', when single hormones have
      both positive and negative effects on multiple physiological systems and (b)
      hormonal conflict between regulatory systems required for different but over
      lapping or linked life-history stages. I illustrate these ideas with examples of
      reproductive anemia, migration-reproduction overlap, and molt-breeding overlap,
      to highlight some of the tremendous opportunities that exist for comparative
      endocrinologists to contribute to mechanistic studies of avian reproduction in an
      evolutionary context.

PMID- 22154574
TI  - Stability of the miniplate osteosynthesis used for sagittal split osteotomy for
      closing an anterior open bite: an experimental study in mini-pigs.
AB  - Bilateral sagittal split osteotomy of the mandible with counterclockwise rotation
      of the occlusal plane alone has traditionally been considered the least stable
      treatment method. Two miniplates on each side of the osteotomy may resolve this
      problem. The authors compared early vertical and transverse stability of a simple
      mandibular advancement (group A), mandibular advancement with counterclockwise
      rotation (CCW) stabilized with one miniplate (group B), and two miniplates (group
      C) on mini-pig mandibles mounted on a custom-made loading unit. Two miniplates
      markedly increased the resistance to vertical bite forces. On a 100-N load, a
      median of dislocation of 0.53 mm, 0.46 mm, and 0.23 mm was achieved in groups A,
      B, and C, respectively. The difference was statistically significant between
      groups A and B in comparison with group C. The results of transverse displacement
      were not statistically significant. The use of two miniplates in larger shifts,
      as well as in CCW cases, increases stability in the vertical direction.

PMID- 22154572
TI  - Gonadotropin-induced changes in oviducal mRNA expression levels of sex steroid
      hormone receptors and activin-related signaling factors in the alligator.
AB  - Oviducts respond to hormonal cues from ovaries with tissue proliferation and
      differentiation in preparation of transporting and fostering gametes. These
      responses produce oviducal microenvironments conducive to reproductive success.
      Here, we investigated changes in circulating plasma sex steroid hormones
      concentrations and ovarian and oviducal mRNA expression to an in vivo
      gonadotropin (FSH) challenge in sexually immature, five-month-old alligators.
      Further, we investigated differences in these observed responses between
      alligators hatched from eggs collected at a heavily-polluted (Lake Apopka, FL)
      and minimally-polluted (Lake Woodruff, FL) site. In oviducts, we measured mRNA
      expression of estrogen, progesterone, and androgen receptors and also beta A and
      B subunits which homo- or heterodimerize to produce the transforming growth
      factor activin. In comparison, minimal inhibin alpha subunit mRNA expression
      suggests that these oviducts produce a primarily activin-dominated signaling
      milieu. Ovaries responded to a five-day FSH challenge with increased expression
      of steroidogenic enzyme mRNA which was concomitant with increased circulating sex
      steroid hormone concentrations. Oviducts in the FSH-challenged Lake Woodruff
      alligators increased mRNA expression of progesterone and androgen receptors,
      proliferating cell nuclear antigen, and the activin signaling antagonist
      follistatin. In contrast, Lake Apopka alligators displayed a diminished increase
      in ovarian CYP19A1 aromatase expression and no increase in oviducal AR
      expression, as compared to those observed in Lake Woodruff alligators. These
      results demonstrate that five-month-old female alligators display an endocrine
      responsive ovarian-oviducal axis and environmental pollution exposure may alter
      these physiological responses.

PMID- 22154575
TI  - Photographs of dental casts or digital models: rating dental arch relationships
      in bilateral cleft lip and palate.
AB  - Yardsticks have been developed to measure dental arch relations in cleft lip and
      palate (CLP) patients as diagnostic proxies for the underlying skeletal
      relationship. Travelling with plaster casts to compare results between CLP
      centres is inefficient so the aim of this study was to investigate the
      reliability of using digital models or photographs of dental casts instead of
      plaster casts for rating dental arch relationships in children with complete
      bilateral cleft lip and palate (CBCLP). Dental casts of children with CBCLP
      (n=20) were included. Plaster casts, digital models and photographs of the
      plaster casts were available for all the children at 6, 9, and 12 years of age.
      All three record formats were scored using the bilateral cleft lip and palate
      (BCLP) yardstick by four observers in random order. No significant differences
      were found for the BCLP yardstick scores among the three formats. The
      interobserver weighted kappa scores were between 0.672 and 0.934. Comparison
      between the formats per observer resulted in weighted kappa scores between 0.692
      and 0.885. It is concluded that digital models and photographs of dental casts
      can be used for rating dental arch relationships in patients with CBCLP. These
      formats are a reliable alternative for BCLP yardstick assessments on conventional
      plaster casts.

PMID- 22154576
TI  - The use of undifferentiated bone marrow stromal cells for sciatic nerve
      regeneration in rats.
AB  - In recent years, cell transplantation has become a focus of attention and
      reliable outcomes have been achieved in regeneration of the sciatic nerve. The
      effect of undifferentiated bone marrow stromal cells (BMSCs) on peripheral nerve
      regeneration was studied using a rat sciatic nerve regeneration model. A 10-mm
      sciatic nerve defect was bridged using an inside-out vein graft (IOVG) filled
      with undifferentiated BMSCs (2 * 10(7)cells/ml). In the control group, the vein
      was filled with phosphate buffer saline alone. The regenerated fibres were
      studied 4, 8 and 12 weeks after surgery. Assessment of nerve regeneration was
      based on functional (walking track analysis), histomorphometric and
      immunohistochemical (Schwann cell detection by S100 expression) criteria. The
      functional study confirmed significant recovery of regenerated axons in the
      IOVG/BMSC group (P<0.05). Quantitative morphometric analyses of regenerated
      fibres showed the number and diameter of myelinated fibres in the IOVG/BMSC group
      were significantly higher than in the control group (P<0.05). This demonstrates
      the potential for using undifferentiated BMSCs in peripheral nerve regeneration
      without the limitations of donor-site morbidity associated with isolation of
      Schwann cells. It also reduces costs because the interval between tissue
      collection and cell injection is reduced and the laboratory procedures are
      simpler compared to undifferentiated BMSCs.

PMID- 22154578
TI  - Comparative ethnobotany and in-the-field antibacterial testing of medicinal
      plants used by the Bulu and inland Kaulong of Papua New Guinea.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The island of New Britain in Papua New Guinea is
      an area of great floristic and cultural diversity that has received little
      attention from ethnobotanists. Here we present the results of a comparative
      medicinal ethnobotanical survey of the Bulu and inland Kaulong; two distinct
      people groups inhabiting lowland rainforest on different sides of the island. A
      high proportion of species are used in the treatment of bacterial infections and
      plants with antibacterial activity were identified in the field using a specially
      developed antibacterial assay kit. Follow up testing with human pathogens was
      used to evaluate active plant material in more detail. MATERIALS AND METHODS:
      Rapid appraisal techniques were used to survey both people groups with all data
      corroborated by three or more separate sources. Plants from both groups were
      tested in-the-field with a portable antibacterial test kit based on the agar
      diffusion assay, using a pressure cooker to sterilise glassware and media. Follow
      up laboratory based tests were carried out using standardised agar dilution
      protocols for drug resistant and drug sensitive strains of Staphylococcus aureus
      and Streptococcus pneumoniae. RESULTS: We find surprisingly little overlap in the
      plant species used by the two people groups with only 1 out of 70 species used
      for the same purpose. There is also a difference in emphasis in the conditions
      treated with 53% of Kaulong medicinal plants dedicated to treating tropical
      ulcers compared with only 8% of in the Bulu group. In-the-field testing
      identified Garcinia dulcis bark (a Kaulong tropical ulcer treatment) to have
      antibacterial activity and follow up tests against a drug resistant strain of
      Staphylococcus aureus (a pathogen implicated in tropical ulcer pathogenesis)
      revealed the crude bark extract to be potently active with an MIC of just 1
      mg/ml. CONCLUSIONS: The results demonstrate extreme differences in medicinal
      plant use between two people groups living a mere 100 km apart and suggests the
      two medicinal plant systems have developed in isolation from one another. In-the
      field antibacterial testing of plant extracts was found to be a valuable
      technique that enabled early identification of active plant material.

PMID- 22154579
TI  - [Unilateral exophthalmos and hypothyroidism].

PMID- 22154580
TI  - Risperidone modulates the cytokine and chemokine release of dendritic cells and
      induces TNF-alpha-directed cell apoptosis in neutrophils.
AB  - Antipsychotic drugs (APDs) that bind mainly to the dopamine D2 receptor or the
      type II 5-HT receptor have been used to ease the symptoms of schizophrenia.
      Several studies have reported that APDs can also regulate the immune response.
      Dendritic cells (DCs) are the major antigen-presenting cells in the immune
      system. DCs can release 5-HT and dopamine to modulate T-cell activation and
      differentiation. In this study, we use the monocyte-derived DCs to investigate
      the drug effects of typical APD (haloperidol) and atypical APD (risperidone) on
      DCs in vitro. Our studies revealed that only risperidone but not haloperidol
      affected the cytokine and chemokine production of mature DCs. Risperidone
      increased the production of IL-10 and MDC as well as the proinflammatory
      cytokines, such as IL-6, IL-8, and TNF-alpha, but decreased the production of IP
      10 and IL-12. Furthermore, the exposure of DCs to risperidone led to lower IFN
      gamma production by T-cells. The results suggested that risperidone can modulate
      the DCs' immune function by inhibiting the potent Th1 cytokines and increasing
      the potent Th2 cytokines. In addition, the production of TNF-alpha by risperidone
      treated mature DCs will induce the death of neutrophils.

PMID- 22154581
TI  - Scaling up of ethanol production from sugar molasses using yeast immobilized with
      alginate-based MCM-41 mesoporous zeolite composite carrier.
AB  - Microporous and mesoporous zeolites, including ZSM-5, H-beta, H-Y, and MCM-41,
      were modified with 3-aminopropyl-triethoxysilane (APTES), then inorganic fillers,
      such as abovementioned zeolites or mesoporous materials, (alpha-AlOOH or gamma
      Al(2)O(3)), were mixed with alginate embedded with yeast; and finally these
      carriers were cross-linked through the double oxirane. The alginate-based
      immobilized yeast with MCM-41 exhibited much shorter fermentation time and higher
      ethanol concentration than pure alginate and other composite carriers with the
      highest cell concentration of 4.8*10(9) cells/mL. The composite carrier maintains
      the highest ethanol productivity of 6.55 g/L/h for 60 days in continuous
      fermentation process, implying good operational durability for commercial
      applications. The reason for the higher bio-catalytical function of the
      immobilized yeast might lay in the uniformly yeast distribution in the bio
      reactor and high yeast cell concentration, which contributed by the improved
      transmission of fermentation media and combined effects of yeast adsorption by
      MCM-41 and embedment by alginate.

PMID- 22154582
TI  - Effect of culture conditions on the competitive interaction between lactate
      oxidizers and fermenters in a biological sulfate reduction system.
AB  - Kinetic constants (MU(max) and K(s)) describing the predominance of lactate
      oxidation and fermentation were determined in chemostat cultures. The kinetics of
      sulfate reduction and lactate utilization were determined from 0.5 to 5d
      residence times at feed sulfate concentrations of 1.0-10.0 g l(-1). The kinetics
      of lactate fermentation in the absence of sulfate were investigated at residence
      times of 0.5-5d. The lactate oxidizers (LO) were characterized by a MU(max) of
      0.2h(-1) and K(s) value of 0.6 g l(-1) compared with a MU(max) of 0.3h(-1) and
      K(s) of 3.3 g l(-1) for the lactate fermenters (LF). Using mathematical models,
      it was shown that LO competed more effectively for lactate at low lactate
      concentrations (<=5 g l(-1)) and high sulfide concentrations (0.5 g l(-1)).
      Lactate fermenters outcompeted the oxidizers under conditions of excess lactate
      (>5 g l(-1)) and low sulfide (0.014-0.088 g l(-1)).

PMID- 22154583
TI  - Methane production from anaerobic co-digestion of the separated solid fraction of
      pig manure with dried grass silage.
AB  - Anaerobic co-digestion of the solid fraction of separated pig manure (SPM) with
      dried grass silage (DGS) was evaluated in three identical continuously stirred
      tank reactors (CSTRs) at 35+/-1  degrees C. The feedstock contained 20% DGS in
      CSTR1, 30% DGS in CSTR2 and 40% DGS in CSTR3 on a volatile solids (VS) basis.
      Organic loading rates (OLR) of 1.0, 1.5, 2.0 and 3.0 kg VS/m(3)/d were studied
      and it was found that the OLR affected the digester performance more than the DGS
      proportion in the feedstock. Tripling the OLR increased volumetric methane yields
      by 88% and decreased specific methane yields by 38%. At the OLR of 3 kg
      VS/m(3)/d, post-methane production potentials of digestates ranged from 38% to
      41% of total methane production potentials of the feedstock. An energy yield
      estimation on a 654-sow pig unit showed that 268-371 MWh/a electricity and 383
      530 MWh/a heat would be generated.

PMID- 22154584
TI  - Microwave-assisted extraction of lignin from triticale straw: optimization and
      microwave effects.
AB  - Presently lignin is used as fuel but recent interests in biomaterials encourage
      the use of this polymer as a renewable feedstock in manufacturing. The present
      study was undertaken to explore the potential applicability of microwaves to
      isolate lignin from agricultural residues. A central composite design (CCD) was
      used to optimize the processing conditions for the microwave (MW)-assisted
      extraction of lignin from triticale straw. Maximal lignin yield (91%) was found
      when using 92% EtOH, 0.64 N H(2)SO(4), and 148  degrees C. The yield and chemical
      structure of MW-extracted lignin were compared to those of lignin extracted with
      conventional heating. Under similar conditions, MW irradiation led to higher
      lignin yields, lignins of lower sugar content, and lignins of smaller molecular
      weights. Except for these differences the lignins resulting from both types of
      heating exhibited comparable chemical structures. The present findings should
      provide a clean source of lignin for potential testing in manufacturing of
      biomaterials.

PMID- 22154585
TI  - Dilute sulfuric acid pretreatment of transgenic switchgrass for sugar production.
AB  - Conventional Alamo switchgrass and its transgenic counterparts with
      reduced/modified lignin were subjected to dilute sulfuric acid pretreatment for
      improved sugar production. At 150  degrees C, the effects of acid concentration
      (0.75%, 1%, 1.25%) and residence time (5, 10, 20, 30 min) on sugar productions in
      pretreatment and enzymatic hydrolysis were investigated, with the optimal
      pretreatment conditions determined for each switchgrass genotype based on total
      sugar yield and the amounts of sugar degradation products generated during the
      pretreatment. The results show that genetic engineering, although did not cause
      an appreciable lignin reduction, resulted in a substantial increase in the ratio
      of acid soluble lignin:acid insoluble lignin, which led to considerably increased
      sugar productions in both pretreatment and enzymatic hydrolysis. At an elevated
      threshold concentration of combined 5-hydroxyfuranmethal and furfural (2.0 g/L),
      the overall carbohydrate conversions of conventional switchgrass and its
      transgenic counterparts, 10/9-40 and 11/5-47, reached 75.9%, 82.6%, and 82.2%,
      respectively.

PMID- 22154586
TI  - The evaluation of various kinetic models for base-catalyzed ethanolysis of palm
      oil.
AB  - In this paper, the kinetics of palm oil ethanolysis with various models have been
      investigated in a temperature range of 25-55  degrees C. The highest yield was
      achieved when the conversion to ethyl ester was 97.5+/-0.5% in the stated
      temperature range, using ethanol:oil molar ratio of 12:1, and 1.0 wt.% sodium
      ethoxide. The level of conformity of the reaction with reversible second order,
      irreversible second order and first order kinetic models were evaluated by means
      of the R(2) values of the linear curves. The ethanolysis showed the best
      conformity with irreversible second order kinetic model with 92-98% level of
      confidence. The reaction rate constants were within 0.018-0.088 dm(3)/mol min and
      the activation energy of the reaction was 42.36 kJ/mol.

PMID- 22154588
TI  - Uterine artery embolization (UAE) for diffuse leiomyomatosis of the uterus:
      clinical and imaging results.
AB  - PURPOSE: The aim of the current study was to evaluate the efficacy of uterine
      artery embolization (UAE) in the management of diffuse uterine leiomyomatosis
      with mid-term follow-up. MATERIALS AND METHODS: All patients who underwent UAE
      between 2008 and 2010 for symptomatic fibroids were analyzed. Among 360 cases, a
      total of 7 patients with diffuse uterine leiomyomatosis diagnosed based on MRI
      were included in this retrospective study. Patient ages ranged from 29 to 38
      (mean 32.7) years. The median follow-up period was 16 (range; 6-31) months. The
      embolic agent was non-spherical polyvinyl alcohol particles. All patients
      underwent follow-up MRI at 3 months after UAE. Uterine volumes were calculated
      using MRI. Menorrhagia symptom changes were assessed at mid-term follow-up.
      RESULTS: There were no technical failures to catheterize the uterine artery and
      no adverse events requiring therapy after UAE. Contrast-enhanced MRI showed
      complete necrosis of the leiomyomatous nodules in 5 patients (71%) 3 months after
      embolization. Two patients (28%) showed mostly leiomyomatous nodules that were
      necrotized, some of which were still viable. All 7 patients with menorrhagia had
      improvement of symptoms at the mid-term follow-up. The initial mean uterine
      volume was 601.30 +/- 533.92 cm(3) and was decreased to a mean of 278.81 +/-
      202.70 cm(3) at 3 months follow-up, for a mean uterus volume reduction rate of
      50.1% (p<0.05). One patient became pregnant 5 months after UAE treatment.
      CONCLUSION: UAE was a highly effective treatment for diffuse uterine
      leiomyomatosis with mid-term durability and may be a valuable alternative to
      hysterectomy.

PMID- 22154589
TI  - Time-resolved phosphorous magnetization transfer of the human calf muscle at 3 T
      and 7 T: a feasibility study.
AB  - Phosphorous ((31)P) magnetization transfer (MT) experiments enable the non
      invasive investigation of human muscle metabolism in various physiological and
      pathological conditions. The purpose of our study was to investigate the
      feasibility of time-resolved MT, and to compare the results of MT experiments at
      3 T and 7 T. Six healthy volunteers were examined on a 3T and a 7 T MR scanner
      using the same setup and identical measurement protocols. In the calf muscle of
      all volunteers, four separate MT experiments (each ~10 min duration) were
      performed in one session. The forward rate constant of the ATP synthesis reaction
      (kATP) and creatine kinase reaction (kCK), as well as corresponding metabolic
      fluxes (FATP, FCK), were estimated. A comparison of these exchange parameters,
      apparent T1s, data quality, quantification precision, and reproducibility was
      performed. The data quality and reproducibility of the same MT experiments at 7 T
      was significantly higher (i.e., kATP 2.7 times higher and kCK 3.4 times higher)
      than at 3 T (p<0.05). The values for kATP (p=0.35) and kCK (p=0.09) at both field
      strengths were indistinguishable. Even a single MT experiment at 7 T provided
      better data quality than did a 4 times-longer MT experiment at 3T. The minimal
      time-resolution to reliably quantify both FATP and FCK at 7 T was ~6 min. Our
      results show that MT experiments at 7 T can be at least 4 times faster than 3 T
      MT experiments and still provide significantly better quantification. This
      enables time-resolved MT experiments for the observation of slow metabolic
      changes in the human calf muscle at 7 T.

PMID- 22154590
TI  - Transarterial embolization for the management of hemarthrosis of the knee.
AB  - BACKGROUND: The purpose of this retrospective study was to evaluate transarterial
      catheter embolization (TAE) for the management of hemarthrosis of the knee in 35
      patients treated at two different hospitals. METHODS: From June 1998 through
      January 2011, 35 patients (22 men and 13 women, mean age 57 years) underwent TAE
      for hemarthrosis of the knee using polyvinyl alcohol particles (PVA particles),
      multi-curled 0.018 in. microcoils or a combination of both. In one patient a
      detachable microcoil was used. Hemarthrosis developed after arthroscopy in 9,
      after trauma in 3, after arthroplasty in 18 and after sepsis in 2 patients. 2
      patients had severe gonarthrosis and in one patient hemarthrosis was due to
      Marfan's syndrome. Angiographies showed abnormal and increased vasculature in 23
      patients, one or more pseudoaneurysms in 8 and arterio-venous fistula in 2
      patients. One patient showed both, pseudoaneurysm and hypervascularization and
      another one pseudoaneurysm and arterio-venous fistula. RESULTS: Technical success
      was achieved in 100%. None of the patients developed procedure-related
      complications such as periarticular skin- or tissue necrosis, including a patient
      who underwent TAE of two different bleeding sources in two consecutive sessions.
      Clinical success was 93.4%. Two patients showed recurrent swelling of the knee,
      377 and 824 days after TAE respectively. However, only one of them required
      secondary TAE because of abnormal and increased vasculature. CONCLUSIONS: In our
      view, TAE is the treatment of choice for the management of hemarthrosis of the
      knee. It is an effective and minimally invasive technique with very low
      complication rates.

PMID- 22154591
TI  - Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent
      chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal
      carcinoma: a phase 3 multicentre randomised controlled trial.
AB  - BACKGROUND: The effect of the addition of adjuvant chemotherapy to concurrent
      chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear.
      We aimed to assess the contribution of adjuvant chemotherapy to concurrent
      chemoradiotherapy versus concurrent chemoradiotherapy alone. METHODS: We did an
      open-label phase 3 multicentre randomised controlled trial at seven institutions
      in China. Randomisation was by a computer-generated random number code. Patients
      were stratified by treatment centre and randomly assigned in blocks of four.
      Treatment allocation was not masked. We randomly assigned patients with non
      metastatic stage III or IV (except T3-4N0) nasopharyngeal carcinoma to receive
      concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent
      chemoradiotherapy alone. Patients in both groups received 40 mg/m(2) cisplatin
      weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as
      2.0-2.27 Gy per fraction with five daily fractions per week for 6-7 weeks to a
      total dose of 66 Gy or greater to the primary tumour and 60-66 Gy to the involved
      neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group
      subsequently received 80 mg/m(2) adjuvant cisplatin and 800 mg/m(2) per day
      fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was
      failure-free survival. We did efficacy analyses in our intention-to-treat
      population. Our trial is ongoing; in this report we present the 2 year survival
      results and acute toxic effects. This trial is registered with
      ClinicalTrials.gov, number NCT00677118. FINDINGS: 251 patients were assigned to
      the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the
      concurrent chemoradiotherapy alone group. After a median follow-up of 37.8 months
      (range 1.3-61.0), the estimated 2 year failure-free survival rate was 86% (95% CI
      81-90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and
      84% (78-88) in concurrent chemoradiotherapy only group (hazard ratio 0.74, 95% CI
      0.49-1.10; p=0.13). Stomatitis was the most commonly reported grade 3 or 4
      adverse event during both radiotherapy (76 of 249 patients in the concurrent
      chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the
      concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of
      205 patients treated with adjuvant chemotherapy). INTERPRETATION: Adjuvant
      cisplatin and fluorouracil chemotherapy did not significantly improve failure
      free survival after concurrent chemoradiotherapy in locoregionally advanced
      nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and
      late toxic effects, but such regimens should not, at present, be used outside
      well-designed clinical trials. FUNDING: Sun Yat-sen University Clinical Research
      5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical
      Programme of Ministry of Health PR China (No 2010-178), and Guangdong Province
      Universities and Colleges Pearl River Scholar Funded Scheme (2010).

PMID- 22154592
TI  - Impact of rotavirus vaccination on childhood gastroenteritis-related mortality
      and hospital discharges in Panama.
AB  - BACKGROUND: Rotavirus vaccination was introduced in Panama in March 2006. This
      study was carried out in order to describe the trends in gastroenteritis-related
      (GER) hospitalizations and mortality in children <5 years of age during the pre-
      and post-vaccination periods. METHODS: Data from the Expanded Program on
      Immunization (Ministry of Health) were used to calculate vaccine coverage. GER
      mortality and hospitalizations were obtained through database review of the
      Contraloria General de la Republica and hospital discharge databases of five
      sentinel hospitals, for the period 2000-2008. Mean rates of GER mortality and
      mean numbers of hospitalizations during the baseline pre-vaccination period (2000
      2005) were compared to those of 2007 and 2008. RESULTS: National coverage for the
      second rotavirus vaccine dose increased from 30% in 2006 to 62% in 2007 and 71%
      in 2008, varying from 62% in the West region to 77% in the Panama region.
      Overall, at 2-years post-vaccine introduction, the GER mortality rate in Panama
      had decreased by 50% (95% confidence interval (CI) 46-54). During 2000-2005, the
      GER mortality rate in children (<1 year) was 73/100 000, decreasing by 45% (95%
      CI 40-51) in 2008. In children aged 1-4 years, the GER mortality rate was
      20.3/100 000 (2000-2005), decreasing by 54% (95% CI 48-60) in 2008. The Panama
      region registered the highest mortality rate reduction (69%; 95% CI 58-81) for
      2008. During 2008, GER hospitalizations among children <5 years of age decreased
      by 30% (95% CI 21-37) from the mean number of hospitalizations during 2000-2005.
      CONCLUSIONS: A substantial reduction in GER mortality and hospitalizations was
      observed following the introduction of rotavirus vaccine in Panama.

PMID- 22154593
TI  - Microbiology and surgical indicators of necrotizing fasciitis in a tertiary
      hospital of southwest Taiwan.
AB  - BACKGROUND: Necrotizing fasciitis is a true surgical emergency. This study was
      undertaken to determine whether clinical indicators could be used to initiate
      early surgery, and to compare the characteristics observed on initial examination
      of necrotizing fasciitis in patients who died and those who survived. METHODS: We
      retrospectively reviewed the medical records of 143 patients with surgically
      confirmed necrotizing fasciitis of the extremities over a period of 3.5 years at
      a tertiary hospital of southwest Taiwan. Differences in mortality, patient
      characteristics, laboratory findings, and hospital course were compared between
      patients who died and those who survived, and between patients with Gram-positive
      infections and those with Gram-negative infections. RESULTS: A patient with a
      fungal infection died. Nine of the 58 patients in the Gram-positive group (15.5%)
      and 12 of the 60 cases in the Gram-negative group (20%) died. Hence a total of 22
      patients died, giving a mortality rate of 15.4%. Hypotension, lower counts of
      total and segmented leukocytes, higher counts of banded leukocytes, and lower
      levels of serum albumin were significantly associated with mortality.
      Monomicrobial infections had a stake of 70.6%, and Vibrio spp were the
      predominant causative agents (26.6%). CONCLUSIONS: Hypotensive shock, severe
      hypoalbuminemia, and increased counts of banded leukocytes can be considered the
      clinical and laboratory risk indicators to initiate early surgery and to predict
      mortality for all types of necrotizing fasciitis. The clinical characteristics of
      Gram-negative infections were more fulminant than those of Gram-positive
      infections.

PMID- 22154594
TI  - Antipsychotic treatment for schizophrenia in the maintenance phase: a systematic
      review of the guidelines and algorithms.
AB  - OBJECTIVE: Antipsychotic treatment strategy for the maintenance phase of
      schizophrenia has been inconsistent in the literature. The purpose of this
      systematic review is to overview recommendations in various guidelines and
      algorithms. METHODS: The guidelines and algorithms for schizophrenia that were
      published or updated in English after 2000 were searched, using Medline, PubMed,
      EMBASE, and PsycINFO with the following key words: guideline, algorithm,
      schizophrenia, and psychosis (last search: July 2011). The reference lists of the
      relevant reports were also examined. RESULTS: Fourteen guidelines and algorithms
      were identified; only five of them clearly defined terms about the maintenance
      phase and treatment. Ten of 11 guidelines and algorithms did not recommend
      discontinuation of antipsychotics within five years; six of them partially
      recommended antipsychotic discontinuation for patients with first-episode
      schizophrenia exclusive. All nine guidelines and algorithms that referred to
      intermittent or targeted antipsychotic strategy endorsed against this strategy.
      Although being a hot topic of controversy, dose reduction of antipsychotics or
      lower dose therapy in the maintenance phase compared to the acute dosage is not
      recommended on the whole concerning atypical antipsychotics, whereas dose
      reduction appears sometimes considered acceptable for typical antipsychotics.
      CONCLUSION: What constitutes maintenance phase and its treatment in schizophrenia
      has not yet been established in the literature. While discontinuation and
      intermittent or targeted strategies are not generally recommended, there is
      controversy regarding dose reduction or lower dose therapy, especially with
      regards to atypical antipsychotics. Further evidence is needed in order to derive
      treatment recommendations on antipsychotics in this critical treatment phase of
      schizophrenia.

PMID- 22154595
TI  - Comparative gene expression study of the chronic exposure to clozapine and
      haloperidol in rat frontal cortex.
AB  - Antipsychotic drugs (APDs) are effective in treating some of the positive and
      negative symptoms of schizophrenia. APDs take time to achieve a therapeutic
      effect which suggests that changes in gene expression are involved in their
      efficacy. We hypothesized that there would be altered expression of specific
      genes associated with the etiology or treatment of schizophrenia in frontal
      cortex of rats that received chronic treatment with a typical APD (haloperidol)
      vs. an atypical APD (clozapine). Rats were administered clozapine, haloperidol,
      or sterile saline intraperitoneally daily for 21days. Frontal cortices from
      clozapine-, haloperidol-, and saline-treated rats were dissected and subjected to
      microarray analysis. We observed a significant (1.5 fold, p<0.05) downregulation
      of 278 genes and upregulation of 73 genes in the clozapine-treated brains vs.
      controls and downregulation of 451 genes and upregulation of 115 genes in the
      haloperidol-treated brains vs. control. A total of 146 genes (130 downregulated
      and 16 upregulated) were significantly altered by both clozapine and haloperidol.
      These genes were classified by functional groups. qRT-PCR (quantitative real-time
      polymerase chain reaction) analysis verified the direction and magnitude of
      change for a group of nine genes significantly altered by clozapine and 11 genes
      significantly altered by haloperidol. Three genes verified by qRT-PCR were
      altered by both drugs: Bcl2-like 1 (Bcl2l1), catechol-O-methyltransferase (Comt),
      and opioid-binding protein/cell adhesion molecule-like (Opcml). Our results show
      that clozapine and haloperidol cause changes in levels of many important genes
      that may be involved in etiology and treatment of schizophrenia.

PMID- 22154596
TI  - Site-specific protein cleavage in vivo by an intein-derived protease.
AB  - Site-specific protein cleavage is a ubiquitous process in cellular protein
      metabolism, yet molecular tools to provide control of protein cleavage inside
      living cells remain scarce. Here, we show that the C-terminal intein fragment of
      the non-canonical Ssp (Synechocystis sp. PCC6803) DnaB S1 split-intein can be
      used as a site-specific protease for in vivo protein cleavage both in bacterial
      and eukaryotic cells. Mutagenesis data indicate a broad tolerance of the intein
      derived protease (IP) toward the amino acid upstream of the cleavage site.
      Furthermore, deletion studies reveal that the recognition sequence for the IP can
      be as short as ten amino acids. The structural features underlying the cleavage
      reaction preclude unintended proteolysis of endogenous proteins, thus ensuring
      that negative effects on cell viability are minimal.

PMID- 22154597
TI  - Disruption and stabilization of beta-cell actin microfilaments differently
      influence insulin secretion triggered by intracellular Ca2+ mobilization or store
      operated Ca2+ entry.
AB  - Latrunculin depolymerizes and jasplakinolide polymerizes beta-cell actin
      microfilaments. Both increase insulin secretion when Ca(2+) enters beta-cells
      during depolarization by glucose, sulfonylureas or potassium. Mouse islets were
      held hyperpolarized with diazoxide, and stimulated with acetylcholine to test the
      role of microfilaments in insulin secretion triggered by intracellular Ca(2+)
      mobilization and store-operated Ca(2+) entry (SOCE). Jasplakinolide slightly
      attenuated Ca(2+) mobilization and did not affect SOCE, but consistently
      inhibited the attending insulin secretion. Latrunculin did not affect Ca(2+)
      changes induced by acetylcholine, but consistently increased insulin secretion,
      its effect being larger in response to Ca(2+) entry than to Ca(2+) mobilization.
      Microfilaments have thus a distinct impact on exocytosis of insulin granules
      depending on the source of triggering Ca(2+).

PMID- 22154598
TI  - Recombinant Whirly1 translocates from transplastomic chloroplasts to the nucleus.
AB  - Whirly1 was shown to be dually located in chloroplasts and nucleus of the same
      cell. To investigate whether the protein translocates from chloroplasts to the
      nucleus, we inserted a construct encoding an HA-tagged Whirly1 into the plastid
      genome of tobacco. Although the tagged protein was synthesized in plastids, it
      was detected in nuclei. Dual location of the protein was confirmed by
      immunocytological analyses. These results indicate that the plastidial Whirly1 is
      translocated from the plastid to the nucleus where it affects expression of
      target genes such as PR1. Our results support a role of Whirly1 in plastid
      nucleus communication.

PMID- 22154599
TI  - A multicenter surveillance of antimicrobial resistance on Stenotrophomonas
      maltophilia in Taiwan.
AB  - BACKGROUND: Stenotrophomonas maltophilia has emerged as an important
      opportunistic pathogen in debilitated hosts. Clinical management of S.
      maltophilia is challenging due to its intrinsic resistance to a variety of
      antibiotics. This study investigated the trend and prevalence of antimicrobial
      resistance in S. maltophilia from a nationwide surveillance study in Taiwan.
      METHODS: S. maltophilia isolates were collected biennially between 1998 and 2008
      as part of the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program
      from medical centers and regional hospitals throughout Taiwan. Minimal inhibitory
      concentrations (MIC) were determined using the Clinical and Laboratory Standards
      Institute reference broth microdilution method. RESULTS: A total of 377 non
      duplicate S. maltophilia isolates were collected from 38 hospitals. The majority
      of the isolates were from the respiratory tract (256, 67.9%), followed by blood
      (48, 12.7%). Overall, 376 (99.7%) isolates were susceptible to minocycline, 362
      (96%) to tigecycline, 311 (82.5%) to trimethoprim/sulfamethoxazole (TMP-SMX), 300
      (79.6%) to levofloxacin, 92 (24.4%) to ceftazidime, and 70 (18.6%) to ticarcillin
      clavulanic acid. The MIC(50)/MIC(90) of minocycline, tigecycline, TMP-SMX,
      levofloxacin, ceftazidime, and ticarcillin-clavulanic acid, were <=0.5/1 MUg/mL,
      0.25/1 MUg/mL, <=0.25/8 MUg/mL, 1/4 MUg/mL, 32/128 MUg/mL, and 64/128 MUg/mL,
      respectively. A trend of increased non-susceptibility to levofloxacin (p=0.014)
      was observed over the 10-year study period. Compared to TMP-SMX-susceptible
      isolates, TMP-SMX-resistant isolates were less susceptible to levofloxacin (54.5%
      vs. 84.9%, p<0.001). CONCLUSION: In this 10-year study, minocycline and TMP-SMX
      remained the two antimicrobials with better in vitro activities against S.
      maltophilia than ceftazidime, levofloxacin, and ticarcillin-clavulanic acid. The
      activity of levofloxacin against S. maltophilia in Taiwan declined during the
      past 10 years.

PMID- 22154600
TI  - Porphyrin effect on the surface morphology of amphiphilic polymers as observed by
      atomic force microscopy.
AB  - Complexes of porphyrin photosensitizers (PPS) with triblock copolymers of
      ethylene- and propylene oxide - Pluronics((r)) - exhibit markedly increased
      activity in the generation of singlet oxygen in aqueous media, as compared to
      pure porphyrins. Pluronics are amphiphilic polymers with surfactant properties
      suitable for a number of medical applications. PPS-Pluronic systems are
      considered as promising agents for photodynamic therapy which implies generation
      of singlet oxygen in the water-based human tissue. Importantly, Pluronics are
      capable of solubilization of not only water-soluble, but also hydrophobic PPS
      providing their transfer into the aqueous phase. It has been shown earlier that
      specific interactions of PPS with Pluronics must play a primary role for the
      photocatalytic properties of PPS-Pluronic systems. In the process of
      solubilization of a hydrophobic porphyrin by a Pluronic, both components are
      dissolved in an organic solvent, which is then removed, and the dry film is re
      dissolved in water. Apparently, the initial binding between the porphyrin and the
      lipophilic part of the polymer takes place already at the stage of the film
      formation. We applied atomic force microscopy (AFM) to visualize structures
      formed by Pluronics upon their interactions with meso-tetraphenylporphyrin (TPP).
      We studied the surface structure of Pluronics((r)) F87, F108 and F127
      crystallized alone or together with TPP on silicon substrates from chloroform
      solutions. We found Pluronics to form similar dendritic structures independently
      of their molecular weight and degree of hydrophobicity. In the presence of TPP,
      though, we observed formation of distinct convex structures on top of the
      Pluronic dendrites. These structures appeared to consist of multiple flat layers
      placed on top of each other. Their sizes varied among the three Pluronics. We
      believe that TPP aggregates interact with the hydrophobic units of Pluronics
      causing the polymer chains to pack themselves in a distinct manner around those
      TPP-containing "cores". These interactions apparently direct formation of
      complexes between the porphyrin and the polymer upon their dissolution in water,
      thus resulting in the encapsulation of TPP aggregates inside a Pluronic micelle.
      A single mechanism for the TPP solubilization by Pluronics is consistent with the
      same catalytic activity of the three TPP-Pluronic systems observed in the
      photooxidation of tryptophan.

PMID- 22154601
TI  - Cotton shoot plays a major role in mediating senescence induced by potassium
      deficiency.
AB  - The objective of this study was to determine the roles of shoot and root in the
      regulation of premature leaf senescence induced by potassium (K) deficiency in
      cotton (Gossypium hirsutum L.). Two contrasting cultivars (CCRI41, more sensitive
      to K deficiency; and SCRC22, a less sensitive cultivar) were selected for self-
      and reciprocal-grafting, using standard grafting (one scion/one rootstock), Y
      grafting (two scions/one rootstock) and inverted Y grafting (one scion/two
      rootstocks) at the seedling stage. Standard grafting was studied in the field in
      2007 and 2008. There were no obvious differences in senescence between CCRI41 and
      SCRC22 scions while supplied with sufficient K. However, SCRC22 scions showed
      significantly greater K content, SPAD values (chlorophyll content), soluble
      protein content and net photosynthetic rates than CCRI41 scions while grown in K
      deficient solution or soil, regardless of rootstock cultivars, grafting types,
      growth stage and growth conditions. Also, SCRC22 scions had greater yield and
      less variation in boll weight either between upper- and lower sympodials, or
      between proximal and distal fruit positions from the main stem in the field under
      K deficiency, probably owing to reduced leaf senescence. Although the effect of
      rootstocks on leaf senescence under K deficiency was significant in some cases,
      the scion cultivars explained the highest percentage of variations within
      grafting treatments. The shoot-to-root feedback signal(s), rather than high shoot
      demand for K nutrition, was involved in the shoot regulation of premature
      senescence in cotton plants, achieved possibly by altering root K uptake.

PMID- 22154602
TI  - Extrapleural paravertebral CT guided fine needle biopsy of subcarinal lymph
      nodes.
AB  - PURPOSE: To report our experience in CT guided extrapleural paravertebral
      subcarinal lymph biopsy using a thin 25 gauge (25 G) thin needle without the need
      of injection of saline to widen the mediastinum. MATERIALS AND METHODS: Biopsy
      was performed using a 25 G needle which was advanced lateral to the vertebral
      body between the endothoracic fascia and the parietal pleura to gain access to
      subcarinal lymph nodes. One hundred and forty one patients were included in the
      study (74 females, 57 males). No artificial widening of the mediastinum using
      saline injection was required. The study was performed in the presence of a
      cytopathologist; sensitivity and specificity rates were calculated. Complications
      were documented for each case especially for pneumothorax and haemorrhage.
      RESULTS: Cytopathological diagnosis was reached in all cases. All re-aspirations
      were done in the same session to reach a primary diagnosis at the time of the
      biopsy. Imunophenotyping study was done in 94 cases to confirm the primary
      diagnosis and to classify the malignant lesions. No pneumothorax was encountered.
      Small haematomas were noted in 5 cases (3.5%). Cytopathology showed a sensitivity
      of 97.2% and specificity of 100%. By adding immunophenotyping a 100% sensitivity
      and specificity was achieved. CONCLUSION: Fine needle aspiration cytology (FNAC)
      using a 25 gauge needle for subcarinal lymph nodes via a percutaneous
      extrapleural paravertebral CT guided approach is a safe, minimally invasive, and
      tolerable procedure yielding a high sensitivity and specificity rates without the
      need of artificial widening.

PMID- 22154603
TI  - Tuberculosis versus lymphoma in the abdominal lymph nodes: a comparative study
      using contrast-enhanced MRI.
AB  - PURPOSE: The purpose of this study was to determine the differential
      characteristics on MRI between tuberculosis and lymphoma in abdominal lymph
      nodes. MATERIALS AND METHODS: We conducted a retrospective analysis for the
      counter, size, signal intensity, enhancement patterns, and anatomic distribution
      of lymph nodes in 57 consecutive patients with documented tuberculosis (28
      patients; 49.1%) and newly diagnosed, untreated lymphoma (29 patients; 50.9%).
      RESULTS: Twenty-four cases (85.7%) in the tuberculosis group were hyperintense on
      T2-weighted images and either hypointense or isointense on T1-weighted images
      with respect to the abdominal wall muscle. All cases in the lymphoma group were
      hyperintense on T2-weighted images and isointense on T1-weighted images with
      respect to the abdominal wall muscle. Concerning the main anatomic distribution
      of lymph nodes, the lymph nodes in the lower paraaortic region were more
      frequently involved in the lymphoma group (48.3%) than in tuberculosis (17.9%,
      p<0.05). Moreover, mesenteric lymph nodes were more often involved in
      tuberculosis (32.1%) than in lymphoma (6.9%, p<0.05). Tuberculous lymphadenopathy
      showed predominantly peripheral enhancement, frequently with a multilocular
      appearance; whereas lymphomatous adenopathy often demonstrated uniform
      homogeneous enhancement (all p<0.001). CONCLUSION: Contrast-enhanced MRI can be
      useful in differentiation between these two entities.

PMID- 22154604
TI  - Colon distension and scan protocol for CT-colonography: an overview.
AB  - This article reviews two important aspects of CT-colonography, namely colonic
      distension and scan parameters. Adequate distension should be obtained to
      visualize the complete colonic lumen and optimal scan parameters should be used
      to prevent unnecessary radiation burden. For optimal distension, automatic carbon
      dioxide insufflation should be performed, preferably via a thin, flexible
      catheter. Hyoscine butylbromide is - when available - the preferred spasmolytic
      agent because of the positive effect on insufflation and pain/burden and its low
      costs. Scans in two positions are required for adequate distension and high polyp
      sensitivity and decubitus position may be used as an alternative for patients
      unable to lie in prone position. The great intrinsic contrast between air or
      tagging and polyps allows the use of low radiation dose. Low-dose protocol
      without intravenous contrast should be used when extracolonic findings are deemed
      unimportant. In patients suspected for colorectal cancer, normal abdominal CT
      scan protocols and intravenous contrast should be used in supine position for the
      evaluation of extracolonic findings. Dose reduction can be obtained by lowering
      the tube current and/or voltage. Tube current modulation reduces the radiation
      dose (except in obese patients), and should be used when available. Iterative
      reconstructions is a promising dose reducing tool and dual-energy CT is currently
      evaluated for its applications in CT-colonography. This review also provides our
      institution's insufflation procedure and scan parameters. 

PMID- 22154605
TI  - CT perfusion measurements of head and neck carcinoma from single section with
      largest tumor dimensions or average of multiple sections: agreement between the
      two methods and effect on intra- and inter-observer agreement.
AB  - PURPOSE: To evaluate the agreement between quantitative CT perfusion measurements
      of head and neck squamous cell carcinoma (SCC) obtained from single section with
      maximal tumor dimension and from average values of multiple sections, and to
      compare intra- and inter-observer agreement of the two methods. METHODS:
      Perfusion was measured for 28 SCC cases using a region of interest (ROI) inserted
      in the single dynamic CT section showing maximal tumor dimension, then using
      average values of multiple ROIs inserted in all tumor-containing sections.
      Agreement between values of blood flow (BF), blood volume (BV), mean transit time
      (MTT) and permeability surface area product (PS) calculated by the two methods
      was assessed. Intra-observer agreement was assessed by comparing repeated
      calculations done by the same radiologist using both methods after 2 months
      blinding period. Perfusion measurements were done by another radiologist
      independently to assess inter-observer agreement of both methods. RESULTS: No
      significant differences were observed between the means of the 4 perfusion
      parameters calculated by both methods, all p values >0.05 The 95% limits of
      agreement between the two methods were (-33.9 to 43)ml/min/100g for BF, (-2.5 to
      2.8)ml/100g for BV, (-4.9 to 3.9)s for MTT and (-17.5 to 18.6)ml/min/100g for PS.
      Narrower limits of agreement were obtained using average of multiple sections
      than with single section denoting improved intra- and inter-observer agreement.
      CONCLUSION: Agreement between both methods is acceptable. Taking the average of
      multiple sections slightly improves intra- and inter-observer agreement.

PMID- 22154607
TI  - Malignant PEComa of the adrenal gland.
AB  - Perivascular epithelioid cell neoplasms, also known as PEComas, are unique
      mesenchymal tumors exhibiting perivascular epithelioid cell differentiation,
      characterized by a mixed myogenic and melanocytic phenotype. PEComas arising in
      visceral organs outside of the kidney, liver, and lung are rare, and often pose
      problems in diagnosis. Examples of this neoplasm originating in the adrenal gland
      are limited. The present report details the clinical and pathologic features of
      an unusual case of a pure epithelioid PEComa (epithelioid angiomyolipoma) of the
      adrenal gland exhibiting clinically malignant behavior in the form of pulmonary
      metastases, a feature not previously described in tumors of this site. The
      diagnosis was supported by immunohistochemical studies demonstrating expression
      of myoid and melanocytic antigens. The present case serves to emphasize the
      potential of PEComa for clinically aggressive behavior and the importance of
      distinguishing this tumor from other epithelioid neoplasms that are more commonly
      encountered in the adrenal gland.

PMID- 22154606
TI  - Nucleic acid recognition by tandem helical repeats.
AB  - Protein domains constructed from tandem alpha-helical repeats have until recently
      been primarily associated with protein scaffolds or RNA recognition. Recent
      crystal structures of human mitochondrial termination factor MTERF1 and Bacillus
      cereus alkylpurine DNA glycosylase AlkD bound to DNA revealed two new
      superhelical tandem repeat architectures capable of wrapping around the double
      helix in unique ways. Unlike DNA sequence recognition motifs that rely mainly on
      major groove read-out, MTERF and ALK motifs locate target sequences and aberrant
      nucleotides within DNA by resculpting the double-helix through extensive backbone
      contacts. Comparisons between MTERF and ALK repeats, together with recent
      advances in ssRNA recognition by Pumilio/FBF (PUF) domains, provide new insights
      into the fundamental principles of protein-nucleic acid recognition.

PMID- 22154608
TI  - Morphology, DNA ploidy and HPV in lung cancer and head and neck cancer.
AB  - Lung cancer and head and neck cancer have similar genotoxic risk factors. While
      the vast majority of lung cancers are caused by cigarette smoking alone, smoking
      together with heavy drinking are the major etiological agents of head and neck
      cancer. In addition, human papilloma virus (HPV) has been identified as an
      important causative factor of tonsillar carcinomas. In contrast, chromosomal
      instability and aneuploidy identifiable by DNA measurement are predominately
      associated with cancer progression. This selective review summarizes our studies
      that aimed to gain a better understanding of the biology and pathology of lung
      cancer and head and neck cancer. In particular, it was attempted (a) to develop a
      microscopy-based tumor classification system that provides insight into the
      genetics of cancer cells and in particular their DNA ploidy, (b) to apply this
      classification system to lung cancer and head and neck cancer and to correlate it
      with clinicopathological parameters and molecular biomarkers, and (c) to analyze
      molecular characteristics and in particular the presence of human papilloma virus
      in lung cancer and head and neck cancer. Therefore, we developed a core
      classification based on the semi-quantitative assessment of the size and type of
      tumor cell nuclei and mitoses. It was found that (1) nuclear and mitosis size
      correlated with the DNA content of the tumor cells, (2) tripolar mitoses were
      indicative of cancer with near-triploid DNA content, (3) morphological and DNA
      parameters indicating variability of the cancer genome were associated with poor
      prognosis of lung cancer patients, (4) HPV-positive head and neck squamous cell
      carcinomas were characterized by smaller tumor nuclei and reduced DNA amount
      compared to HPV-negative carcinomas, and (5) HPV is associated with lung cancer
      in certain geographical regions of the world.

PMID- 22154610
TI  - Coupling infectious diseases, human preventive behavior, and networks--a
      conceptual framework for epidemic modeling.
AB  - Human-disease interactions involve the transmission of infectious diseases among
      individuals and the practice of preventive behavior by individuals. Both
      infectious diseases and preventive behavior diffuse simultaneously through human
      networks and interact with one another, but few existing models have coupled them
      together. This article proposes a conceptual framework to fill this knowledge gap
      and illustrates the model establishment. The conceptual model consists of two
      networks and two diffusion processes. The two networks include: an infection
      network that transmits diseases and a communication network that channels inter
      personal influence regarding preventive behavior. Both networks are composed of
      same individuals but different types of interactions. This article further
      introduces modeling approaches to formulize such a framework, including the
      individual-based modeling approach, network theory, disease transmission models
      and behavioral models. An illustrative model was implemented to simulate a
      coupled-diffusion process during an influenza epidemic. The simulation outcomes
      suggest that the transmission probability of a disease and the structure of
      infection network have profound effects on the dynamics of coupled-diffusion. The
      results imply that current models may underestimate disease transmissibility
      parameters, because human preventive behavior has not been considered. This issue
      calls for a new interdisciplinary study that incorporates theories from
      epidemiology, social science, behavioral science, and health psychology.

PMID- 22154609
TI  - Feasibility and diagnostic accuracy of a low radiation exposure protocol for
      prospective ECG-triggering coronary MDCT angiography.
AB  - AIM: To compare the feasibility, accuracy, and effective radiation dose (ED) of
      multidetector computed tomography (MDCT) in the detection of coronary artery
      disease using a combined ED-saving strategy including prospective
      electrocardiogram (ECG) triggering with a short x-ray window and a body mass
      index (BMI)-adapted imaging protocol using adaptive statistical iterative
      reconstruction (ASIR; group 1), in comparison with a prospective ECG triggering
      strategy alone (group 2). MATERIALS AND METHODS: One hundred and seventy patients
      scheduled for invasive coronary angiography (ICA) were evaluated. Fourteen
      patients were not eligible for MDCT. The remaining 156 patients were randomized
      to group 1 (78 patients) and group 2 (78 patients). Eight and 11 patients in
      groups 1 and 2, respectively, were excluded after randomization because the
      patients' heart rates were >65 beats/min. MDCT images were assessed for
      feasibility, signal-to-noise ration (SNR), and contrast-to-noise ratio (CNR),
      accuracy in detection of coronary stenoses >50% versus ICA and for ED. RESULTS:
      The feasibility, SNR, CNR, accuracy in a segment-based and patient-based model
      were similar in both groups (97 versus 95%, 14.5 +/- 3.9 versus 14.2 +/- 4.1, 16
      +/- 4.6 versus 16.5 +/- 4.4, 95 versus 94% and 97 versus 99%, respectively). The
      ED in group 1 was 72% lower than in group 2 (2.1 +/- 1.2 versus 7.5 +/- 1.8 mSv,
      respectively; p<0.01). CONCLUSIONS: The use of a multi-parametric ED saving
      protocol results in a significant reduction in ED without a negative impact on
      accuracy.

PMID- 22154611
TI  - Health information seeking and use outside of the medical encounter: is it
      associated with race and ethnicity?
AB  - Increasing numbers of adults in the United States of America (USA) are seeking
      and using health information within their medical encounters. The theory of
      uncertainty management suggests that patients reduce health care uncertainty by
      increasing their understanding of disease etiology or treatment options,
      improving patient-doctor communication, and enhancing knowledge of disease self
      management through health information seeking. However, research shows racial and
      ethnic minorities are less likely than Whites to seek health information and use
      it in their physician visits. How racial and ethnic minorities use health
      information outside of their medical encounters is unknown. In this study we used
      data from the 2007 USA Health Tracking Household survey, a nationally
      representative survey of civilian, non-institutionalized Americans (n = 12,549).
      Using logistic regression we found African Americans were no different from
      Whites in seeking health information and using it when they talked with their
      doctors. Latinos were significantly less likely than Whites to seek health
      information and less likely to use it when they talked with their doctors. But,
      among those who sought health information, African Americans and Latinos were
      significantly more likely than Whites to use health information to change their
      approach to maintaining their health and better understand how to treat
      illnesses. Also, education significantly moderated the relationship between
      race/ethnicity and health information seeking. However, results were mixed for
      education as a moderator in the relationship between race/ethnicity and health
      information use. Future research should focus on interventions to improve how
      African Americans and Latinos interface with providers and ensure that health
      information sought and used outside of their medical encounters augments
      treatment protocols.

PMID- 22154612
TI  - Adaptation of hand movements to double-step targets and to distorted visual
      feedback: evidence for shared mechanisms.
AB  - Visuomotor adaptation of hand movements has been studied with two paradigms:
      double-step targets and distorted visual feedback. Here we investigate whether
      both procedures are based on a common adaptive mechanism. Subjects adapted either
      to double-step targets or to distorted feedback, each requiring a change of
      response angle by -15 degrees . The magnitude of adaptation was larger with
      rotated feedback but magnitude of aftereffects was comparable, suggesting that
      the difference was due to strategic effects rather than visuomotor recalibration.
      Most importantly, subjects who adapted to double-step targets and were then
      exposed to rotated feedback performed as well as subjects who had fully adapted
      to rotated feedback, i.e., there was nearly 100% transfer from double-steps to
      rotations; likewise, the transfer from rotations to double-steps was almost 100%.
      From this we conclude that both types of adaptation share a common mechanism for
      recalibration.

PMID- 22154613
TI  - Women with an avoidant attachment style show attenuated estradiol responses to
      emotionally intimate stimuli.
AB  - The current study examined neuroendocrine processes associated with emotional
      intimacy in humans. Despite the importance of this aspect of close relationships,
      emotional intimacy has received much less attention in neuroendocrine research
      compared to other aspects of close relationships. In this study, participants
      viewed movie clips depicting an emotionally intimate parent-child interaction or
      other, non-intimate themes, and we assessed whether depictions of emotional
      intimacy increased levels of estradiol, a steroid hormone associated with
      attachment and caregiving processes. We also examined whether estradiol responses
      were moderated by individual differences in attachment avoidance, or people's
      discomfort with closeness and intimacy. Our findings revealed that, among single
      participants, estradiol levels increased in response to the emotionally intimate
      clip, but this effect was not observed among currently partnered participants.
      Moreover, the effects of emotional intimacy were moderated by gender and
      attachment avoidance, such that highly avoidant women showed smaller increases in
      estradiol after watching the emotionally intimate clip. Women's avoidance was
      unrelated to estradiol responses in the non-intimate control conditions, however,
      suggesting that the effects of avoidance were specific to intimate contexts.
      Taken together, the current findings contribute to our understanding of the
      biological bases of attachment and caregiving processes. They also highlight the
      potential role of estradiol in avoidant individuals' regulation of closeness and
      intimacy.

PMID- 22154615
TI  - Adeno-associated virus-mediated osteoprotegerin gene transfer protects against
      joint destruction in a collagen-induced arthritis rat model.
AB  - OBJECTIVE: To evaluate the in vivo joint protection effect of recombinant adeno
      associated virus-mediated gene transfer of human osteoprotegerin (rAAV-hOPG).
      METHODS: Collagen-induced arthritis (CIA) rat model was established. CIA rats
      were randomly divided into three groups: CIA control group (PBS), rAAV-EGFP
      (enhanced green fluorescent protein) group and rAAV-hOPG (100 MUL/d) group, which
      received corresponding intra-articular injection treatment. The thickness of the
      palms and soles, arthritis index, radiological score, pathological score, bone
      damage factor and protein expression of inflammatory factors were measured and
      compared with normal control group rats. RESULTS: Positive fluorescence of frozen
      section confirmed that rAAV-hOPG was efficiently transduced into the synovial
      tissues of test rats. In rAAV-hOPG group compared with CIA control group, the
      radiological score was 30.18% lower (P<0.05); the expression of OPG protein was
      93.41% higher (P<0.05); the expression of matrix metalloproteinase-3 (MMP-3)
      protein was 35.38% lower (P<0.05); however, the expression of IL-1beta was not
      significant; the scores of pannus and inflammation in rAAV-hOPG group have no
      significant difference. CONCLUSION: These results suggest that adeno-associated
      virus-mediated transfer of human osteoprotegerin is effectively transducted into
      the synovial tissues of CIA model, and protects against articular cartilage and
      bone destruction, but has no obvious efficiency on inflammation. The results also
      demonstrate that gene transfer using rAAV-hOPG may be a feasible and effective
      therapeutic candidate to treat or prevent joint destruction in inflammatory
      arthritis.

PMID- 22154614
TI  - Idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm, and
      inflammatory pericarditis--retrospective analysis of 11 case histories.
AB  - Retroperitoneal fibrosis, inflammatory aortic aneurysm, and pericardial and
      mediastinal fibrosis are characterized by infiltration of immuno-inflammatory
      cells and deposition of thickened fibrous tissues. Several recent studies
      suggested that an immunoglobulin-G4 (IgG4)-related immunological mechanism may
      play a role in these diseases. By searching the clinical database of patients
      admitted to our department between 2000 and 2010, we summarized the clinical data
      of 11 patients who were diagnosed to have these disorders. The diagnoses were
      idiopathic retroperitoneal fibrosis (8 cases), mediastinal and/or pericardial
      fibrosis (4 cases), inflammatory abdominal aneurysm (2 cases), and inflammatory
      coronary periarteritis (1 case). Hypertension, diabetes, and dyslipidemia were
      found in 45%, 36%, and 55%, respectively, in these patients, and they were all
      either current or former smokers. Two patients with pericardial involvement
      showed a rushed clinical course, resulting in in-hospital death. Serum levels of
      IgG were elevated in 67%, and soluble interleukin-2 receptor was elevated in 75%,
      when measured. Immunohistochemical analysis showed marked infiltration of IgG4
      positive plasma cells in the pericardium in patients who died of constrictive
      pericarditis. Our data support the notion that immune-inflammatory mechanism,
      which might be IgG4-related sometimes, may play a role in idiopathic
      retroperitoneal fibrosis, inflammatory aortic aneurysm, and
      mediastinal/pericardial fibrosis, although clinical course may differ
      substantially.

PMID- 22154616
TI  - Oesophageal motility impairment in type I myotonic dystrophy: usefulness of high
      resolution manometry.

PMID- 22154618
TI  - Umbilical cord blood: lessons learned and lingering challenges after more than 20
      years of basic and clinical research.
AB  - During the last 23 years, cord blood research has played important roles both in
      experimental and clinical hematology. Cord blood-derived hematopoietic stem and
      progenitor cells have been shown to possess particular biological features and
      their study has been very important in our understanding of hematopoietic
      development. Today, >20,000 umbilical cord blood (UCB) transplants have been
      performed worldwide and ~460,000 UCB units are being stored in >47 UCB banks
      worldwide. Here a brief overview on some of the most relevant issues regarding
      cord blood research is presented.

PMID- 22154617
TI  - Effect of CYP1A1 MSPI polymorphism on the relationship between TP53 mutation and
      CDKN2A hypermethylation in non-small cell lung cancer.
AB  - BACKGROUND AND AIMS: The molecular mechanisms of lung cancer susceptibility have
      not been fully understood. Although it has been described that germline
      polymorphisms are associated with either mutation or methylation of genes, the
      link between gene polymorphisms and gene-gene interactions has not been
      investigated. Therefore, we conducted this study to determine whether
      CYP1A1/GSTM1 polymorphisms can affect the relationship between TP53 mutation and
      CDKN2A hypermethylation in lung cancer. METHODS: This study included 196 primary
      non-small cell lung cancer (NSCLC) patients. CYP1A1 MSPI and GSTM1 polymorphisms
      were characterized through PCR-RFLP on DNA isolated from peripheral lymphocytes.
      TP53 mutations of exons 5 through 9 and CDKN2A promoter hypermethylation in both
      cancer tissues and corresponding normal tissues were analyzed by direct
      sequencing and methylation-specific PCR (MSP) respectively. RESULTS: TP53
      mutation in the tumor was associated with squamous cell histology and CDKN2A
      methylation was associated with older age (>=60 years), heavy smoking (>30 pack
      years), squamous cell histology and advanced stage (stage II-IV). After adjusting
      for age, sex, smoking degree, histology type and TNM stage, the correlation
      between TP53 mutation and CDKN2A methylation was significant in patients with
      CYP1A1 risk genotype (p = 0.038), but not in those with CYP1A1 homogeneity wild
      genotype (p = 0.151). CONCLUSIONS: This may suggest that TP53 mutation and CDKN2A
      methylation specifically interact to promote lung tumorigenesis in subjects with
      CYP1A1 risk genotype but not in those with CYP1A1 wild-type homozygotes, implying
      different pathways for the development of lung carcinoma with respect to CYP1A1
      polymorphism.

PMID- 22154619
TI  - Autoimmunity and Turner's syndrome.
AB  - Turner Syndrome (TS) is a common genetic disorder, affecting female individuals,
      resulting from the partial or complete absence of one sex chromosome, and
      occurring in approximately 50 per 100,000 liveborn girls. TS is associated with
      reduced adult height and with gonadal dysgenesis, leading to insufficient
      circulating levels of female sex steroids and to infertility. Morbidity and
      mortality are increased in TS but average intellectual performance is within the
      normal range. TS is closely associated to the presence of autoantibodies and
      autoimmune diseases (AID), especially autoimmune thyroiditis and inflammatory
      bowel disease. Despite the fact that the strong association between TS and AID is
      well known and has been widely studied, the underlying immunopathogenic mechanism
      remains partially unexplained. Recent studies have displayed how TS patients do
      not show an excess of immunogenic risk markers. This is evocative for a higher
      responsibility of X-chromosome abnormalities in the development of AID, and
      particularly of X-genes involved in immune response. For instance, the long arm
      of the X chromosome hosts a MHC-locus, so the loss of that region may lead to a
      deficiency in immune regulation. Currently no firm guidelines for diagnosis
      exist. In conclusion, TS is a condition associated with a number of autoimmune
      manifestations. Individuals with TS need life-long medical attention. As a
      consequence of these findings, early diagnosis and regular screening for
      potential associated autoimmune conditions are essential in the medical follow-up
      of TS patients.

PMID- 22154620
TI  - Modern methods for delivery of drugs across the blood-brain barrier.
AB  - The blood-brain barrier (BBB) is a highly regulated and efficient barrier that
      provides a sanctuary to the brain. It is designed to regulate brain homeostasis
      and to permit selective transport of molecules that are essential for brain
      function. Unfortunately, drug transport to the brain is hampered by this almost
      impermeable, highly selective and well coordinated barrier. With progress in
      molecular biology, the BBB is better understood, particularly under different
      pathological conditions. This review will discuss the barrier issue from a
      biological and pathological perspective to provide a better insight to the
      challenges and opportunities associated with the BBB. Modern methods which can
      take advantage of these opportunities will be reviewed. Applications of
      nanotechnology in drug transport, receptor-mediated targeting and transport, and
      finally cell-mediated drug transport will also be covered in the review. The
      challenge of delivering an effective therapy to the brain is formidable;
      solutions will likely involve concerted multidisciplinary approaches that take
      into account BBB biology as well as the unique features associated with the
      pathological condition to be treated.

PMID- 22154621
TI  - Mono-methoxy-poly(3-hydroxybutyrate-co-4-hydroxybutyrate)-graft-hyper-branched
      polyethylenimine copolymers for siRNA delivery.
AB  - A class of non-viral siRNA vectors consisting of biodegradable
      poly(hydroxyalkanoates) (PHA) grafted onto branched poly(ethyleneimine) (bPEI, 25
      kDa) was synthesized and evaluated for siRNA delivery. The mPHA-g-bPEI copolymers
      were synthesized through Michael addition between acrylated mono-methoxy
      poly(hydroxyalkanoates) (mPHA-acrylated) and bPEI with various block length
      poly(hydroxyalkanoates) from 1300 to 2900 Da. Our research showed that mPHA-g
      bPEI copolymers could effectively bind siRNA, protect it from degradation by
      nucleases and efficiently release the complexed siRNA in the presence of low
      concentrations of polyanionic heparin. The particle size of mPHA-g-bPEI/siRNA
      complexes was <200 nm with zeta-potential between 33 and 43 mV. mPHA-g-bPEI
      copolymers displayed low cytotoxicity compared to unmodified bPEI and efficient
      cellular uptake of Cy3-siRNA in A549 cells by flow cytometry and confocal
      microscopy. siRNA delivery efficiency of the copolymers was assessed by siRNA
      against luciferase in cultured A549-Luc and MCF-7-Luc cells. Those mPHA-g-bPEI
      copolymers revealed a higher transfection efficiency and lower cytotoxicity than
      bPEI in two cell lines. Furthermore, a remarkable knockdown of luciferase
      expression of mPHA-g-bPEI (mAP2) complex (up to 85%) in vitro was found to be
      equivalent to that of commercially available transfection agent LipofectamineTM
      2000.

PMID- 22154622
TI  - The control of endothelial cell adhesion and migration by shear stress and matrix
      substrate anchorage.
AB  - Endothelial cells constitute the natural inner lining of blood vessels and
      possess anti-thrombogenic properties. This characteristic is frequently used by
      seeding endothelial cells on vascular prostheses. As the type of anchorage of
      adhesion ligands to materials surfaces is known to determine the mechanical
      balance of adherent cells, we investigated herein the behaviour of endothelial
      cells under physiological shear stress conditions. The adhesion ligand
      fibronectin was anchored to polymer surfaces of four physicochemical
      characteristics exhibiting covalent and non-covalent attachment as well as high
      and low hydrophobicity. The in situ analysis combined with cell tracking of shear
      stress-induced effects on cultured isolated cells and monolayers under venous
      (0.5 dyn/cm(2)) and arterial (12 dyn/cm(2)) shear stress over a time period of 24
      h revealed distinct differences in their morphological and migratory features.
      Most pronounced, unidirectional and bimodal migration patterns of endothelial
      cells in or against flow direction were found in dependence on the type of
      substrate-matrix anchorage. Combined by an immunofluorescent analysis of the
      actin cytoskeleton, cell-cell junctions, cell-matrix adhesions, and matrix
      reorganization these results revealed a distinct balance of laminar shear stress,
      cell-cell contacts and substrate-matrix anchorage in affecting endothelial cell
      fate under flow conditions. This analysis underlines the importance of materials
      surface parameters as well as primary and secondary adhesion ligand anchorage in
      the context of artificial blood vessels for future therapeutic devices.

PMID- 22154624
TI  - USPSTF and FDA: PSA and 5ARIs.

PMID- 22154625
TI  - L'USPSTF et la FDA: l'APS et les I5AR.

PMID- 22154623
TI  - Ribosomal and protein coding gene based multigene phylogeny on the family
      Streptomycetaceae.
AB  - The phylogenetic relationship among the three genera of the family
      Streptomycetaceae was examined using the small and large subunit ribosomal RNA
      genes, and the gyrB, rpoB, trpB, atpD and recA genes. The total stretches of the
      analyzed ribosomal genes were 4.2kb, and those of five protein coding genes were
      4.5 kb. The resultant phylogenetic trees confirmed that each genus formed an
      independent clade in the majority of cases. The G+C contents of rRNA genes were
      56.9-58.9 mol%, and those of protein coding genes were 65.4-72.4 mol%, the latter
      being closer to those of the genomic DNAs. The average nucleotide sequence
      identity between the organisms were 94.1-96.4% for rRNA genes and 85.7-90.6% for
      protein coding genes, thus indicating that protein coding genes can give higher
      resolution than rRNA genes. In addition, the protein coding gene trees were more
      stable than the rRNA gene trees, supported by higher bootstrap values and other
      treeing algorithms. Moreover, the genome data of six Streptomyces species
      indicated that many protein coding genes exhibited higher correlations with
      genome relatedness. The combined gene sequences were also shown to give a better
      resolution with higher stability than any single genes, though not necessarily
      more correlated with genome relatedness. It is evident from this study that the
      rRNA gene based phylogeny can be misleading, and also that protein coding genes
      have a number of advantages over the rRNA genes as the phylogenetic markers
      including a high correlation with the genome relatedness.

PMID- 22154626
TI  - PSA testing still essential.

PMID- 22154627
TI  - La mesure de l'APS demeure essentielle.

PMID- 22154628
TI  - Cooperative Group Cancer Clinical Trials: An NCIC Clinical Trials Group
      Perspective.

PMID- 22154629
TI  - Intrahepatic extension of renal cell carcinoma tumor thrombus causing Budd-Chiari
      syndrome.

PMID- 22154630
TI  - A multicentre single-blind randomized controlled trial comparing bipolar and
      monopolar transurethral resection of the prostate.
AB  - INTRODUCTION: Monopolar transurethral resection of the prostate (TURP) is the
      gold standard surgical therapy for men with lower urinary tract symptoms due to
      benign prostatic hyperplasia. Although generally considered safer, TURP
      experience is limited in Canada. METHODS: Forty-three patients from 5 Canadian
      centres were randomized to TURP with either bipolar or monopolar platforms.
      Patients underwent baseline determinations of American Urological Association
      (AUA) symptom score, peak urinary flow rate, post-void residual bladder volume
      and transrectal ultrasound prostate volume. Primary outcome measures were
      improvement in AUA symptom score, quality of life assessment and bother
      assessment. Secondary outcomes included procedural times, duration of
      catheterization, length of hospitalization, complications and the degree of
      thermal artifact in tissue specimens. Patients were followed for 6 months.
      RESULTS: Twenty-two patients were treated with bipolar and 21 with monopolar
      TURP. Preoperative demographics were not statistically different between groups.
      Postoperative data collection times were equivalent in AUA symptom, quality of
      life, bother and sexual function assessments. No differences were observed in the
      procedure time (60.7 min, bipolar vs. 47.4, monopolar) or the duration of
      urethral catheterization (1.5 days, bipolar vs. 1.1, monopolar). More patients in
      the bipolar group were discharged on the same day of surgery. There were no
      differences in the degree of tissue thermal artifact or complication rate.
      CONCLUSION: This trial suggests equivalent short-term outcomes for men undergoing
      monopolar or bipolar TURP.

PMID- 22154631
TI  - Monopolar vs. bipolar TURP: assessing their clinical advantages.

PMID- 22154632
TI  - Acute reversible kidney injury secondary to bilateral ureteric obstruction.
AB  - BACKGROUND: Acute reversible kidney injury (ARKI) secondary to bilateral ureteric
      obstruction (BUO) is a common urological problem. Our goals were to describe the
      etiology, management and outcomes of such patients identified between 2006 and
      2009 and to compare them with a similar historical study published in 1982.
      METHODS: Chart review was performed on 49 patients with AKRI secondary to BUO.
      ARKI was defined as >=33% decrease in serum creatinine after intervention. Those
      with malignant and benign causes of obstruction were identified and management
      and outcome data were collected. RESULTS: Of these 49 patients, 83% had BUO
      secondary to malignancy, 28% of these presenting for the first time. Prevalence
      of bladder cancer was increased (p = 0.04) and cervix trended lower (p = 0.07)
      compared with the earlier study; prostate cancer was unchanged (p = 0.51). The
      average survival was 239 days; 90% of patients died within a year after
      presenting with BUO from a malignant etiology. Compared with the 1982 group,
      there were trends towards a decrease in the frequency of retroperitoneal fibrosis
      (p = 0.08) and an increase in bilateral ureteric calculi (p = 0.16) in the benign
      group. CONCLUSIONS: Patients with ARKI secondary to BUO most likely have an
      underlying malignancy, with almost a third of them being diagnosed for the first
      time. Prevalence of bladder cancer increased while cervical cancer trended lower.
      The cause for the former is unclear; the latter may be due to aggressive
      screening. Prostate cancer remained unchanged despite the widespread
      implementation of prostate-specific antigen testing. Patients with an underlying
      malignancy do poorly and those with a newly diagnosed malignancy do worst. Those
      with ARKI secondary to benign causes did well.

PMID- 22154633
TI  - The association between tumour density and prostate cancer recurrence following
      radical prostatectomy.
AB  - PURPOSE: Tumour density (TD) may be an independent prognostic factor in men with
      prostate cancer. The purpose of this study was to evaluate the association
      between prostate cancer TD and recurrence following radical prostatectomy.
      MATERIALS AND METHODS: Between 1995 and 2007, 645 patients from The Ottawa
      Hospital or Memorial Sloan-Kettering Cancer Center who had cancer and prostate
      volumes measured from radical prostatectomy specimens. Tumour density was defined
      as the relative tumour to prostate volume (tumour volume/prostate volume) and
      recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/mL and
      rising, or postoperative use of radiation or hormonal therapy. Associations
      between TD and recurrence are adjusted for preoperative PSA, prostatectomy
      Gleason sum, tumour stage and margin status. RESULTS: Median follow-up was 40.8
      months. Tumour density was associated with preoperative PSA, Gleason sum, tumour
      stage and surgical margin status (all p < 0.0001). As a continuous variable, TD
      predicted recurrence-free survival (adjusted HR 1.34 per 10% increase in TD; p =
      0.04). As a categorical variable, the group of patients with a TD of >10% had a
      2.7 times greater hazard of recurrence compared to patients with a TD <5% (95%CI
      1.41, 5.19; p = 0.003). Despite the independent association between TD and
      recurrence, the clinical value of TD remains in question as the discriminative
      performance (area under the curve) of predictive models only improved from 0.865
      to 0.876. CONCLUSIONS: Prostate cancer TD is associated with known prognostic
      factors and is also independently predictive of recurrence following radical
      prostatectomy.

PMID- 22154634
TI  - The pursuit of the "perfect" biomarker in prostate cancer.

PMID- 22154635
TI  - A modified approach to patient's selection with improved clinical outcomes in
      sacral nerve modulation.
AB  - INTRODUCTION: Since the marketing of the percutaneous permanent tined leads
      (PPTL), many centres rely solely on these instead of the percutaneous nerve
      evaluation (PNE) as a screening tool. At our centre, we routinely perform PNE.
      Moreover, with our limited hospital resources, we have adopted a stricter
      definition of success in the patient selection process using an improvement of
      more than 60% as a cut-off point. This study presents our experience with sacral
      nerve stimulation using PPTL as an adjunct to PNE to improve the outcome of the
      screening method for patients suffering from refractory voiding dysfunction.
      METHODS: We reviewed the charts of 106 patients who underwent a PNE between 2001
      and 2008. The outcome of the procedures, the complication rates and its long-term
      effect were reviewed. RESULTS: Overall, 116 PNE were performed and it was
      successful in 54%. Forty-five out of the 62 patients with a successful PNE
      underwent the stage I procedure. Of these, 93% had a successful stage I and were
      later implanted with the implantable pulse generator (IPG). The remaining 12
      patients underwent the simultaneous implantation of the PPTL and IPG using the
      open procedure and it was successful in 10 of them. CONCLUSION: The PNE is a good
      adjunct to the staged procedure to select the appropriate candidates for sacral
      nerve stimulation, especially with limited resources.

PMID- 22154636
TI  - Helping patients with voiding dysfunction: What are our current options?

PMID- 22154637
TI  - Childhood sexual trauma in women with interstitial cystitis/bladder pain
      syndrome: a case control study.
AB  - BACKGROUND: The impact of early lifetime trauma on symptom severity and quality
      of life of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) has
      not been fully elucidated. We wanted to determine and compare the prevalence and
      impact of childhood traumatic events, with an emphasis on childhood sexual abuse,
      on patient symptoms, quality of life and other biopsychosocial parameters.
      METHODS: Subjects (female patients with IC/BPS and controls without IC/BPS)
      completed psychosocial phenotyping questionnaires, including a
      demographics/history form, and validated questionnaires focused on presenting
      symptoms (IC symptom indices, pain), psychosocial parameters (depression,
      anxiety, pain catastrophizing, sexual functioning, social support) and quality of
      life. Participants also completed the Childhood Traumatic Events Scale. RESULTS:
      Questionnaires were completed by 207 IC/BPS patients and 117 controls matched for
      age, partner status and education. It was found that before 17 years of age, the
      IC/BPS cases reported higher prevalence of "raped or molested" compared to
      controls (24.0% vs. 14.7%; p = 0.047). Within the IC/BPS group, cases reporting
      previous sexual abuse endorsed greater sensory pain, depression and poorer
      physical quality of life at the present time compared to IC cases without a
      sexual abuse history. In the controls only, those reporting previous sexual abuse
      endorsed more depression, anxiety, stress, social maladjustment poorer mental
      quality of life in the present time. When the analysis was corrected for
      potential multiple comparison error, none of the findings remained significant in
      either the IC/BPS or control groups. INTERPRETATION: Childhood traumatic events,
      in particular sexual abuse and extreme illness, are reported as more common in
      IC/BPS patients than controls. Early trauma, such as the occurrence of sexual
      abuse, is associated with some differences in patient adjustment (e.g., pain,
      quality of life, depression) but this impact appears to be, at most, very modest.

PMID- 22154638
TI  - Furthering the prostate cancer screening debate (prostate cancer specific
      mortality and associated risks).
AB  - Screening for prostate cancer remains a contentious issue. As with other cancer
      screening programs, a key feature of the debate is verification of cancer
      specific mortality reductions. Unfortunately the present evidence, two systematic
      reviews and six randomized controlled trials, have reported conflicting results.
      Furthermore, half of the studies are poor quality and the evidence is clouded by
      key weaknesses, including poor adherence to screening in the intervention arm or
      high rates of screening in the control arm. In high quality studies of prostate
      cancer screening (particularly prostate-specific antigen), in which actual
      compliance was anticipated in the study design, there is good evidence that
      prostate cancer mortality is reduced. The numbers needed to screen are at least
      as good as those of mammography for breast cancer and fecal occult blood testing
      for colorectal cancer. However, the risks associated with prostate cancer
      screening are considerable and must be weighed against the advantage of reduced
      cancer-specific mortality. Adverse events include 70% rate of false positives,
      important risks associated with prostate biopsy, and the serious consequences of
      prostate cancer treatment. The best evidence demonstrates prostate cancer
      screening will reduce prostate cancer mortality. It is time for the debate to
      move beyond this issue, and begin a well-informed discussion on the remaining
      complex issues associated with prostate cancer screening and appropriate
      management.

PMID- 22154639
TI  - HIFU: Definitely ready for prime time.

PMID- 22154640
TI  - HIFU ablation is not a proven standard treatment for localized prostate cancer.

PMID- 22154641
TI  - Correction.

PMID- 22154642
TI  - In memoriam.

PMID- 22154644
TI  - Extrahypophyseal expression of gonadotropin subunits in pejerrey Odontesthes
      bonariensis and effects of high water temperatures on their expression.
AB  - It has been traditionally accepted that the gonadotropins (GtHs), follicle
      stimulating hormone (FSH) and luteinizing hormone (LH), are synthesized and
      secreted only by the pituitary. However, the presence of theses hormones in
      extrapituitary tissues has been demonstrated in mammals, and more recently also
      in fish. In this study, we cloned the cDNAs and characterized the expression of
      FSH-beta, LH-beta, and glycoprotein hormone alpha (GPH-alpha) subunits from brain
      and gonads of male and female pejerrey Odontesthes bonariensis at different
      stages of gonadal maturation. In situ hybridization revealed that, in addition to
      their classical location in pituitary cells, the three GtH transcripts were also
      located in the gonads. FSH-beta and GPH-alpha subunits were found in the
      cytoplasm of oogonia, previtellogenic and vitellogenic oocytes in ovaries. LH
      beta expression was detected in previtellogenic and vitellogenic oocytes but not
      in oogonia. In males, the three subunits were expressed in spermatogonia and to a
      lesser extent in spermatocytes. Exposure of fish to high water temperatures that
      impair pejerrey reproduction also induced a decrease of extrahypophyseal
      expression of GtH subunits.

PMID- 22154645
TI  - The expression of insulin and insulin receptor mRNAs is regulated by nutritional
      state and glucose in rainbow trout (Oncorhynchus mykiss).
AB  - Many species of fish, including rainbow trout, possess multiple INS- and IR
      encoding mRNAs. In this study, rainbow trout (Oncorhynchus mykiss) were used as a
      model to study the regulation of INS (INS1, INS2) and IR (IR1, IR2, IR3, and IR4)
      mRNA expression by nutritional state and glucose. In the nutritional state study,
      fish were either fed continuously, fasted (4 or 6 weeks), or fasted 4 weeks, then
      refed for 2 weeks. Nutritional state regulated INS and IR mRNA expression in a
      subtype- and tissue-specific manner. A 4-week fast reduced INS1 expression in
      endocrine pancreas (Brockmann body) and of INS1 and INS2 in brain, whereas a 6
      week fast reduced the expression of both INS1 and INS2 in pancreas but only of
      INS1 in brain. Refeeding only restored INS2 levels in pancreas. In adipose
      tissue, by contrast, a 4-week fast increased INS1 expression, and a 6-week fast
      increased the expression of both INS1 and INS2. Nutritional state also modulated
      the pattern of IR mRNA expression. Fasting for 4 weeks resulted in no significant
      change in IR expression. Prolonged fasting (6 weeks) increased the expression of
      IR4 mRNA in the pancreas, adipose tissue, cardiac muscle, and gill; however,
      fasting decreased expression of IR3 mRNA in liver. Refeeding restored fasting
      associated increases in IR4 expression in pancreas, adipose tissue, cardiac
      muscle, and gill, but had no effect on the fasting-associated decrease in IR3
      expression in liver. Glucose differentially regulated the expression of INS and
      IR mRNAs in Brockmann bodies and liver pieces incubated in vitro, respectively.
      Low glucose (1 mM) reduced pancreatic expression of both INS1 and INS2 mRNAs
      compared to levels observed at 4 or 10 mM glucose. In the liver, IR1 and IR2 mRNA
      expression was insensitive to glucose concentration, whereas expression of IR3
      and IR4 was attenuated at 1 and 10 mM compared to 4 mM glucose. These findings
      indicate that the pattern of INS and IR expression in selected tissues is
      regulated by nutritional state and glucose.

PMID- 22154646
TI  - Four stanniocalcin genes in teleost fish: structure, phylogenetic analysis,
      tissue distribution and expression during hypercalcemic challenge.
AB  - Stanniocalcin (STC), first isolated from the corpuscles of Stannius (CS) of
      teleost fishes and a systemic regulator of mineral metabolism, is present in all
      vertebrates as two isoforms, STC1 and STC2, encoded by separate genes. Here we
      show that the genome of Tetraodon nigroviridis, and other teleosts, possess
      duplicate genes for each STC isoform, designated stc1-a and -b, and stc2-a and 
      b. Stc1-a was cloned from CS, stc2-a from muscle and the two novel cDNAs, stc1-b
      and stc2-b, from brain. However, stc2-b was isolated as a conjoined (read
      through) transcript with bod1 (bi-orientation defective 1, or FAM44B), and two
      additional alternative conjoined transcripts were also isolated. The predicted
      STC products shared the typical vertebrate 10 conserved cysteine residues and N
      linked glycosylation motifs, in addition to specific features. Gene structure was
      generally conserved with four exons and three introns with the exception of stc1
      a which gained an extra intron in exon three, originating one extra exon. Gene
      order and synteny is also maintained across vertebrates and the cpeb4 gene
      identified in the homologue region of the chordate Ciona was linked to vertebrate
      stc2 but not stc1. Immunohistochemistry in different species revealed that STC1-A
      was found only in CS and in a few cells in kidney. STC1-B had a restricted
      expression and was more prominent in the gills. STC2-A was detected in a variety
      of tissues, including pituitary, with most abundant immunoreaction in kidney
      cells and gill rakers and the CS was negative. Expression of stc1-a in CS of
      Tetraodon was 15-fold (p<0.05) up-regulated 2 h after transfer from 2.9 mM Ca(2+)
      to 10 mM Ca(2+) water and down-regulated after 12 hours to 11-fold lower than 2.9
      mM Ca(2+) fish (p<0.05). With the exception of stc1-a in CS, low expression
      levels and high individual variation were generally found for the expression of
      stc transcripts in kidney and gills, with no statistically significant changes in
      response to the hypercalcemic shock. In conclusion, both stc1 and stc2 genes are
      represented by paralogues in teleosts genomes and the analysis performed suggests
      that only stc1-a in the CS is involved in extracellular calcium regulation. The
      widespread distribution of stcs in fish tissues supports pleiotropic roles.

PMID- 22154647
TI  - Updating a near-infrared multivariate calibration model formed with lab-prepared
      pharmaceutical tablet types to new tablet types in full production.
AB  - Determining active pharmaceutical ingredient (API) tablet concentrations rapidly
      and efficiently is of great importance to the pharmaceutical industry in order to
      assure quality control. Using near-infrared (NIR) spectra measured on tablets in
      conjunction with multivariate calibration has been shown to meet these
      objectives. However, the calibration is typically developed under one set of
      conditions (primary conditions) and new tablets are produced under different
      measurement conditions (secondary conditions). Hence, the accuracy of
      multivariate calibration is limited due to differences between primary and
      secondary conditions such as tablet variances (composition, dosage, and
      production processes and precision), different instruments, and/or new
      environmental conditions. This study evaluates application of Tikhonov
      regularization (TR) to update NIR calibration models developed in a controlled
      primary laboratory setting to predict API tablet concentrations manufactured in
      full production where conditions and tablets are significantly different than in
      the laboratory. With just a few new tablets from full production, it is found
      that TR provides reduced prediction errors by as much as 64% in one situation
      compared to no model-updating. TR prediction errors are reduced by as much as 51%
      compared to local centering, another calibration maintenance method. The TR
      updated primary models are also found to predict as well as a full calibration
      model formed in the secondary conditions.

PMID- 22154648
TI  - Development of a simple detector response function generation program: the
      CEARDRFs code.
AB  - A simple Monte Carlo program named CEARDRFs has been developed to generate very
      accurate detector response functions (DRFs) for scintillation detectors. It
      utilizes relatively rigorous gamma-ray transport with simple electron transport,
      and accounts for two phenomena that have rarely been treated: scintillator non
      linearity and the variable flat continuum part of the DRF. It has been proven
      that these physics and treatments work well for 3*3" and 6*6" cylindrical NaI
      detector in CEAR's previous work. Now this approach has been expanded to cover
      more scintillation detectors with various common shapes and sizes. Benchmark
      experiments of 2*2" cylindrical BGO detector and 2*4*16" rectangular NaI detector
      have been carried out at CEAR with various radiactive sources. The simulation
      results of CEARDRFs have also been compared with MCNP5 calculations. The
      benchmark and comparison show that CEARDRFs can generate very accurate DRFs (more
      accurate than MCNP5) at a very fast speed (hundred times faster than MCNP5). The
      use of this program can significantly increase the accuracy of applications
      relying on detector spectroscopy like prompt gamma-ray neutron activation
      analysis, X-ray fluorescence analysis, oil well logging and homeland security.

PMID- 22154643
TI  - Rapid steroid hormone actions initiated at the cell surface and the receptors
      that mediate them with an emphasis on recent progress in fish models.
AB  - In addition to the classic genomic mechanism of steroid action mediated by
      activation of intracellular nuclear receptors, there is now extensive evidence
      that steroids also activate receptors on the cell surface to initiate rapid
      intracellular signaling and biological responses that are often nongenomic.
      Recent progress in our understanding of rapid, cell surface-initiated actions of
      estrogens, progestins, androgens and corticosteroids and the identities of the
      membrane receptors that act as their intermediaries is briefly reviewed with a
      special emphasis on studies in teleost fish. Two recently discovered novel
      proteins with seven-transmembrane domains, G protein-coupled receptor 30 (GPR30),
      and membrane progestin receptors (mPRs) have the ligand binding and signaling
      characteristics of estrogen and progestin membrane receptors, respectively, but
      their functional significance is disputed by some researchers. GPR30 is expressed
      on the cell surface of fish oocytes and mediates estrogen inhibition of oocyte
      maturation. mPRalpha is also expressed on the oocyte cell surface and is the
      intermediary in progestin induction of oocyte maturation in fish. Recent results
      suggest there is cross-talk between these two hormonal pathways and that there is
      reciprocal down-regulation of GPR30 and mPRalpha expression by estrogens and
      progestins at different phases of oocyte development to regulate the onset of
      oocyte maturation. There is also evidence in fish that mPRs are involved in
      progestin induction of sperm hypermotility and anti-apoptotic actions in ovarian
      follicle cells. Nonclassical androgen and corticosteroid actions have also been
      described in fish models but the membrane receptors mediating these actions have
      not been identified.

PMID- 22154649
TI  - X-ray fluorescence analysis of ancient and medieval brass artifacts from south
      Moravia.
AB  - This paper deals with an investigation of archeological finds using X-ray
      fluorescence analysis and microanalysis. The main aim of the investigation was to
      prove the production of brass in the South Moravian Region (part of the Czech
      Republic) in former times. The probable brass production technology is described.
      Various objects dating back to Antiquity and to the Middle Ages were investigated
      using two X-ray fluorescence systems, and the results of the analyses are
      discussed. The measurements showed, e.g., that fragments of Roman scale armor and
      a belt fitting dating back to Antiquity were made of brass. Brass was also
      identified on the surfaces of various ancient and medieval molds and melting
      pots.

PMID- 22154650
TI  - Local therapy is critical in localised pelvic rhabdomyosarcoma: experience of the
      International Society of Pediatric Oncology Malignant Mesenchymal Tumor (SIOP
      MMT) committee.
AB  - BACKGROUND: Localised pelvic rhabdomyosarcomas (pRMS) are rare tumours with a
      poorer prognosis than the majority of RMS. This study analysed patient outcome
      according to the type of local therapy delivered and the effect of disease
      related factors on prognosis. PATIENTS AND METHODS: 97 children with localised
      pRMS were enrolled in the SIOP-MMT84, 89 and 95 studies. After primary surgery or
      biopsy, all children received ifosfamide/actinomycin/vincristine-based
      chemotherapy. Radiotherapy and surgery were planned in patients failing to
      achieve complete remission. RESULTS: Median age at diagnosis was 52 months [5
      months-18 years]. IRS staging was I for five patients, II for 15 and III for 77.
      Patients had embryonal RMS (N = 41), alveolar RMS (N = 29), botryoid RMS (N = 3),
      or not otherwise specified RMS (N = 24). OUTCOME: 87 patients achieved local
      control (90%), 37 relapsed (43%), mainly locally (84%). With a median follow-up
      of more than 10 years [4-22 years], 5-year OS was 66% (95% CI: 56-75%) and EFS
      was 52% (95% CI: 42-61%). Among the 18 IRS-I/II patients treated without
      radiotherapy, 15 survived. Seven out of the 20 IRS-III patients treated without
      local therapy died. In multivariate analysis, IRS staging, age greater than 10
      years and lymph node involvement had a negative impact on OS. Perineal/perianal
      locations had a trend towards a worse prognosis. CONCLUSION: pRMS still have a
      relatively poor prognosis. Radiotherapy or brachytherapy is necessary for all IRS
      III patients including those with radiological complete remission after
      neoadjuvant chemotherapy with or without surgery. Radiotherapy may be withheld in
      IRS-I patients and children under 3 years with IRS-II pRMS.

PMID- 22154651
TI  - The phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235
      is effective in inhibiting regrowth of tumour cells after cytotoxic therapy.
AB  - PURPOSE: Regrowth of tumour cells between cycles of chemotherapy is a significant
      clinical problem. Treatment strategies where antiproliferative agents are used to
      inhibit tumour regrowth between chemotherapy cycles are attractive, but such
      strategies are difficult to test using conventional monolayer culture systems.
      METHODS: We used the in vitro tumour spheroid model to study regrowth of 3-D
      colon carcinoma tissue after cytotoxic therapy. Colon carcinoma cells with wild
      type or mutant phosphatidyl inositol 3-kinase catalytic subunit (PI3KCA) or KRAS
      alleles were allowed to form multicellular spheroids and the effects of different
      pharmacological compounds were studied after sectioning and staining for relevant
      markers of cell proliferation and apoptosis. RESULTS: Studies using colon cancer
      cells with gene disruptions suggested that the phosphoinositide 3-kinase (PI3K)
      mammalian target of rapamycin (mTOR) pathway was essential for proliferation in 3
      D culture. The dual PI3K-mTOR inhibitor NVP-BEZ235, currently in clinical trials,
      was found to inhibit phosphorylation of the mTOR target 4EBP1 in 3-D cultured
      cells. The ability of NVP-BEZ235 to inhibit tumour cell proliferation and to
      induce apoptosis was markedly more pronounced in 3-D cultures compared to
      monolayer cultures. It was subsequently found that NVP-BEZ235 was effective in
      inhibiting regrowth of 3-D cultured cells after treatment with two cytotoxic
      inhibitors of the ubiquitin-proteasome system (UPS), methyl-13-hydroxy-15
      oxokaurenoate (MHOK) and bortezomib (Velcade(r)). CONCLUSIONS: The dual PI3K-mTOR
      inhibitor NVP-BEZ235 was found to reduce cell proliferation and to induce
      apoptosis in 3-D cultured colon carcinoma cells, NVP-BEZ235 is a promising
      candidate for use in sequential treatment modalities together with cytotoxic
      drugs to reduce the cell mass of solid tumours.

PMID- 22154652
TI  - Pitfalls and limitations of a single-centre, retrospectively derived prognostic
      score for phase I oncology trial participants - reply to Fussenich et al.: a new,
      simple and objective prognostic score for phase I cancer patients.

PMID- 22154654
TI  - Intragastric nitration by dietary nitrite: implications for modulation of protein
      and lipid signaling.
AB  - Inorganic nitrite, derived from the reduction of nitrate in saliva, has recently
      emerged as a protagonist in nitric oxide ((*)NO) biology as it can be univalently
      reduced to (*)NO, in the healthy human stomach. Important physiological
      implications have been attributed to nitrite-derived (*)NO in the
      gastrointestinal tract, namely modulation of host defense, blood flow, mucus
      formation and motility. At acidic pH, nitrite generates different nitrogen oxides
      depending on the local microenvironment (redox status, gastric content, pH,
      inflammatory conditions), including (*)NO, nitrogen dioxide ((*)NO(2)),
      dinitrogen trioxide (N(2)O(3)), and peroxynitrite. Thus, the gastric environment
      is a significant source of nitrating and nitrosating agents, especially in
      individuals consuming a nitrate/nitrite-rich diet on a daily basis. Both, the
      gastric lumen and mucosa contain putative targets for nitration, not only
      proteins and lipids from ingested aliments but also endogenous proteins secreted
      by the oxyntic glands. The physiological and functional consequences of nitration
      of gastric mediators will impact on local processes including food digestion and
      ulcerogenesis. Additionally, gastric nitration products (such as nitrated lipids)
      may be absorbed and affect systemic pathways. Thus, dietary ingestion of nitrate
      will have direct consequences for endogenous protein nitration, as indicated by
      our preliminary data.

PMID- 22154655
TI  - Regarding Secker TJ, Herve R, Keevil CW. Adsorption of prion and tissue proteins
      to surgical stainless steel surfaces and the efficacy of decontamination
      following dry and wet storage conditions. J Hosp Infect 2011;78:251-255.

PMID- 22154656
TI  - Contacts with mental health services before suicide: a comparison of Indigenous
      with non-Indigenous Australians.
AB  - OBJECTIVE: Most people who die by suicide never seek help, particularly members
      of ethnic minorities. This study compared the prevalence of contacts with mental
      health services, types of services accessed and factors related to help-seeking
      behaviors by Indigenous and non-Indigenous Australians. METHOD: All suicides by
      Indigenous and non-Indigenous persons from Queensland, Australia, during the
      period 1994-2007 were analyzed using descriptive statistics and logistic
      regression models. RESULTS: Non-Indigenous suicide cases were almost two times
      more likely than Indigenous counterparts to have ever received help for mental
      health problems (43.3% vs. 23.8%). The most common source of help for Indigenous
      persons was inpatient care, while for non-Indigenous persons, it was general
      practitioners. Factors increasing the likelihood of service utilization by
      Indigenous persons were suicide attempt in last year, living in metropolitan area
      and not being married. Among non-Indigenous persons, these factors were recent
      communication of suicidal intent or suicide attempt, recent treatment for
      physical illness and problematic consumption of alcohol. CONCLUSIONS: Indigenous
      Australians die by suicide at a rate twice higher than the non-Indigenous
      population, yet they are significantly less likely to seek professional help for
      mental health concerns. Help-seeking behavior among Indigenous Australians at
      risk of suicide should be promoted thorough provision of culturally appropriate
      services.

PMID- 22154657
TI  - When patients do not hurt: silent acute abdomen in a patient with schizophrenia.
AB  - The phenomenon of pain insensitivity in schizophrenia and other psychotic
      disorders has been described since the early 20th century. Medical conditions
      often present atypically in the seriously mentally ill patient. Emergency
      physicians, primary care practitioners, surgeons and psychiatrists must maintain
      a high index of suspicion for acute abdomen in seriously mentally ill patients
      who may exhibit a diminished or absent perception of pain. The authors present a
      case of an atypical presentation of acute abdomen in a patient with
      schizophrenia.

PMID- 22154658
TI  - Psychosis associated with bromvalerylurea abuse in a patient with traumatic brain
      injury.

PMID- 22154659
TI  - Oral-paliperidone-induced tardive dyskinesia: a case report.
AB  - OBJECTIVES: Tardive dyskinesia (TD) is generally considered the most severe
      extrapyramidal sequelae of antipsychotic treatments. METHOD: Case report.
      RESULTS: We present a 20-year-old woman with previous treatment of risperidone 6
      7 mg daily for approximately 4 years. She developed TD 2 years later after
      switching to paliperidone 9 mg daily. To the best of our knowledge, she is the
      first case report of having direct paliperidone-induced TD. Immediate treatments
      including paliperidone dose reduction to 6 mg daily, clonazepam 1.5 mg daily and
      trihexyphenidyl 2 mg daily were performed for 1 month, and her symptoms were
      relieved eventually after switching to clozapine 75 mg daily. CONCLUSION:
      Although second-generation antipsychotics such as paliperidone are considered to
      have a lowered risk of developing TD, this case could bring awareness to
      clinicians of the possibility of TD with the use of any antipsychotics.

PMID- 22154660
TI  - An exemplar for evidence-based nursing practice using the Magnet((r)) model as
      the framework for change: oral feeding practice in the neonatal intensive care
      unit.
AB  - Implementation of research evidence into practice can be challenging in areas
      such as the neonatal intensive care unit (NICU), where the environment is complex
      and rapidly changing and caregiving goals have shifted from simply infant
      survival to supporting positive long-term neurodevelopmental outcomes. Clinical
      nurse specialists (CNS) are ideally positioned to use research to obtain new
      knowledge, innovations, and improvements in care as part of an interdisciplinary
      team. The authors describe the role of the CNS in changing NICU culture around
      feeding infants, an important and frequent nursing activity, with the Magnet((r))
      model as the framework for change.

PMID- 22154661
TI  - Temporal and spatial relations in sentential reasoning.
AB  - The mental model theory postulates that the meanings of assertions, and knowledge
      about their context can modulate the logical meaning of sentential connectives,
      such as "if" and "or". One known effect of modulation is to block the
      representation of possibilities to which a proposition refers. But, modulation
      should also add relational information, such as temporal order, to models of
      possibilities. Three experiments tested this prediction. Experiment 1 showed that
      individuals spontaneously matched the tense of their conclusions (in Portuguese)
      to embody implied, but unexpressed, temporal relations in conditional premises.
      Experiment 2 demonstrated the same phenomenon in inferences from disjunctions.
      Experiment 3 showed that the number of such implicit relations in inferences from
      conditionals affects both accuracy and the speed of reasoning. These results
      support the modulation hypothesis.

PMID- 22154662
TI  - Combination of two chromophores: synthesis and PDT application of porphyrin
      pentamethinium conjugate.
AB  - A general method for the synthesis of a novel porphyrin with pentamethine
      periphery substitution is described. The combination of two chromophoric systems,
      a porphyrin macrocycle and a polymethine moiety was achieved by transformation of
      tetrapyridyl porphyrin. The synthetic strategy included conversion of the
      tetrapyridyl porphyrin to its corresponding 2,4-dinitrophenylpyridinuim salt,
      which was subsequently converted to tetrakis(meso-pentamethinium salt) on the
      porphyrin core. This novel porphyrin exhibited PDT properties as manifested by
      the induction of apoptosis in the myeloid cell line HL-60 and the effective
      reduction of amelanotic melanoma in nude mice.

PMID- 22154663
TI  - Virtual ligand screening of alpha-glucosidase: Identification of a novel potent
      noncarbohydrate mimetic inhibitor.
AB  - 5-Thiazoleacetamide derivatives of AR122 and AR125 were screened as alpha
      glucosidase inhibitors by in silico high-throughput screening from commercial
      drug-like small compound libraries. Inhibition of alpha-glucosidase with AR122
      and AR125 is time dependent: with no preincubation, AR122 and AR125 are
      relatively moderate inhibitors, but interestingly, after a 120 min incubation,
      they were 50-fold more potent (AR122: IC(50)=2.47 MUM and AR125: IC(50)=27.1
      MUM). Plots of ln [residual alpha-glucosidase activity %] versus preincubation
      time show a pseudo-first order kinetics for both inhibitors. Through dialysis of
      enzyme-inhibitor complexes, no activity recovery was shown. These results suggest
      that AR122 and AR125 constitute a new class of noncarbohydrate mimetic inhibitor
      with an irreversible mechanism.

PMID- 22154664
TI  - Discovery of potent small molecule inhibitors of DYRK1A by structure-based
      virtual screening and bioassay.
AB  - In this study, six novel dual-specificity tyrosine phosphorylation regulated
      kinase 1A (DYRK1A) inhibitors with IC(50) values ranging from 1.51 to 88.13 MUM
      were successfully identified through virtual screening and in vitro plus cell
      based bioassay. Compound 5 with IC(50) value of 1.51 MUM is the most potent hit
      against DYRK1A in vitro, while compound 3 exhibited the most potent activity in
      cultured cells. The inhibition mechanism was explored by molecular docking
      approach. This study may provide a start point for further mechanism based study
      as well as discovery of drug candidate against Down syndrome (DS).

PMID- 22154665
TI  - New substituted C-19-andrographolide analogues with potent cytotoxic activities.
AB  - Andrographolide, the major diterpenoid lactone from Andrographis paniculata, is
      toxic against cancer cells. In the present study, we investigated the structure
      activity relationships (SARs) of 19 andrographolide analogues which were
      synthesized by modification at the three hydroxyl groups. A number of the
      andrographolide analogues showed much higher cytotoxic activities than that of
      the parent compound on cancer cells including P-388, KB, COL-2, MCF-7, LU-1 and
      ASK cells. SAR studies of the synthetic analogues indicated that the introduction
      of silyl ether or triphenylmethyl ether group into C-19 of the parent compound
      led to increase in toxicity against the cancer cells. The 19-O-triphenylmethyl
      ether analogue 18 showed higher cytotoxic activity than the potent anticancer
      drug ellipticine, and this analogue may serve as a potential structure lead for
      the development of new anticancer drugs.

PMID- 22154653
TI  - Role of reactive oxygen and nitrogen species in the vascular responses to
      inflammation.
AB  - Inflammation is a complex and potentially life-threatening condition that
      involves the participation of a variety of chemical mediators, signaling
      pathways, and cell types. The microcirculation, which is critical for the
      initiation and perpetuation of an inflammatory response, exhibits several
      characteristic functional and structural changes in response to inflammation.
      These include vasomotor dysfunction (impaired vessel dilation and constriction),
      the adhesion and transendothelial migration of leukocytes, endothelial barrier
      dysfunction (increased vascular permeability), blood vessel proliferation
      (angiogenesis), and enhanced thrombus formation. These diverse responses of the
      microvasculature largely reflect the endothelial cell dysfunction that
      accompanies inflammation and the central role of these cells in modulating
      processes as varied as blood flow regulation, angiogenesis, and thrombogenesis.
      The importance of endothelial cells in inflammation-induced vascular dysfunction
      is also predicated on the ability of these cells to produce and respond to
      reactive oxygen and nitrogen species. Inflammation seems to upset the balance
      between nitric oxide and superoxide within (and surrounding) endothelial cells,
      which is necessary for normal vessel function. This review is focused on defining
      the molecular targets in the vessel wall that interact with reactive oxygen
      species and nitric oxide to produce the characteristic functional and structural
      changes that occur in response to inflammation. This analysis of the literature
      is consistent with the view that reactive oxygen and nitrogen species contribute
      significantly to the diverse vascular responses in inflammation and supports
      efforts that are directed at targeting these highly reactive species to maintain
      normal vascular health in pathological conditions that are associated with acute
      or chronic inflammation.

PMID- 22154666
TI  - Electrophysiological impact of trazodone on the dopamine and norepinephrine
      systems in the rat brain.
AB  - Previous study has documented the long-term effects of the antidepressant
      trazodone on the serotonin (5-HT) system. The present work examined the impact of
      sustained trazodone on ventral tegmental area (VTA) dopamine (DA) and locus
      ceruleus (LC) norepinephrine (NE) neurons firing activity, and characterized its
      effects at 5-HT(2C), 5-HT(2A) receptors and alpha1- and alpha2-adrenoceptors.
      Electrophysiological recordings were carried out in anesthetized rats.
      Subcutaneously implanted minipumps delivered vehicle or trazodone (10 mg/kg/day)
      for 2 or 14 days. Administration of trazodone for 2 and 14 days did not alter the
      firing activity of DA neurons. Systemic injection of trazodone, however, reversed
      the inhibitory effect of the 5-HT(2C) receptor agonist Ro 60,0175 on the DA
      neuronal firing, suggesting an antagonistic action of trazodone at this receptor.
      Administration of trazodone for 2 days significantly enhanced the NE neurons
      firing. Despite a return of the NE neurons firing rate to the baseline following
      14-day trazodone, the percentage of neurons discharging in burst was increased by
      this regimen. Administration of trazodone for 14 days enhanced the tonic
      activation of postsynaptic alpha2-adrenoceptors, as indicated by the
      disinhibitory effect of the alpha2-adrenoceptor antagonist idazoxan on
      hippocampus pyramidal neurons firing. The inhibitory effect of acute trazodone on
      dorsal raphe (DR) 5-HT neurons firing was shown to be through the 5-HT(1A)
      receptor. Systemic injection of trazodone reversed the inhibitory action of 5
      HT(2A) agonist DOI on the NE neurons firing rate, indicating its antagonistic
      action at 5-HT(2A) receptors. The enhancement in alpha2-adrenergic transmission
      by trazodone, and its 5-HT(2A) and 5-HT(2C) receptor antagonism may contribute to
      its therapeutic action in major depression.

PMID- 22154667
TI  - A prospective cohort study of pelvic support changes among nulliparous,
      multiparous, and pre- and post-menopausal women.
AB  - OBJECTIVE(S): To evaluate whether vaginal delivery affects maternal pelvic
      support beyond the puerperium by comparing pelvic support changes between
      nulliparas and multiparas, and whether menopause predisposes women to develop
      prolapse that protrudes beyond the hymen by comparing its occurrence between pre-
      and post-menopausal subjects. STUDY DESIGN: Women who presented to our gynecology
      clinic for routine care and returned for follow-up after 36 +/- 3 months were
      evaluated for pelvic support changes using the Pelvic Organ Prolapse
      Quantification, which measured changes in 1-cm increments. Exclusion criteria
      were women who were seen in the urogynecology clinic or had hysterectomy, vaginal
      repair, continence procedure, childbirth during the study period, or radiation
      therapy. RESULTS: The proportion that experienced a 1-cm (21/101 vs. 27/164,
      p=0.374) and at least a 2-cm (5/101 vs. 9/164, p=0.849) descent of the leading
      edge of prolapse was similar between our 101 nulliparous and 164 multiparous
      subjects. At the initial examination, nine multiparas and one nullipara had
      prolapse outside the hymen (9/164 vs. 1/101, p=0.056). The proportion that
      developed pelvic support defect, which protruded beyond the hymen, was similar
      between the two groups (1/100 vs. 5/155, p=0.243). Eighty-five of our 265
      subjects were post-menopausal while 180 were pre-menopausal. The proportions that
      developed a 1-cm (18/85 vs. 30/180, p=0.374) and at least a 2-cm (7/85 vs. 7/180,
      p=0.140) descent of the leading edge of prolapse were similar between the two
      groups. Eight post-menopausal and two pre-menopausal women had prolapse outside
      the hymen at the initial examination (8/85 vs. 2/180, p=0.002). More post
      menopausal subjects developed support defect, which protruded beyond the hymen,
      than their pre-menopausal counterparts (5/77 vs. 1/178, p=0.010). Logistic
      regression showed that menopause (p=0.019) is an independent risk factor for
      developing prolapse which protruded outside the hymen, while parity (p=0.168) and
      interaction between menopause and parity (p=0.606) are not significantly
      associated with its occurrence. CONCLUSION(S): Vaginal birth has little effect on
      the pelvic support changes beyond the puerperium while menopause predisposes
      women to prolapse their pelvic organ outside the hymen.

PMID- 22154669
TI  - Inhibition of intraerythrocytic proteasome retards the generation of hemorphins.
AB  - Hemorphins are a set of hemoglobin-derived opioid peptides. The production
      mechanism of these structural overlap peptides remains unclear. Based on the
      sequences of hemorphins, it could be inferred that hemorphins are probably
      generated by cleavage of hemoglobin beta chain at sites favored by the
      chymotrypsin-like protease. 20S proteasome possesses the chymotrypsin-like
      activity and still persists in mature erythrocytes. This study attempts to
      clarify whether the intraerythrocytic proteasome involves in the formation of
      hemorphins. Hemorphins containing hemorphin-7 and V-hemorphin-7 are isolated by
      immunoprecipitation from culture supernatant of human erythrocytes. Bortezomib
      inhibits the chymotrypsin-like activity of intraerythrocytic proteasome and
      prevents the yield of hemorphins in a dose-dependent manner. The present study
      suggests that intraerythrocytic proteasome contributes to the generation of
      hemorphins.

PMID- 22154668
TI  - Comparison of saline infusion sonohysterography and hysteroscopy in diagnosis of
      premenopausal women with abnormal uterine bleeding.
AB  - OBJECTIVE: The aim of this study was to compare the diagnostic effectiveness of
      transvaginal sonography (TVS), saline infusion sonohysterography (SIS), and
      diagnostic hysteroscopy (HS), with the pathologic specimen as a gold standard
      diagnostic method, in detecting endometrial pathology in premenopausal women with
      abnormal uterine bleeding. STUDY DESIGN: This prospective cohort study was
      conducted at Zeynep Kamil Education and Training Hospital, Istanbul, Turkey, and
      included 89 premenopausal women. All participants were examined first by TVS,
      further investigated with SIS and HS, and finally dilatation and curettage was
      performed when needed. The results obtained from these three methods were
      compared with the pathologic diagnoses. The positive and negative likelihood
      ratios (LR+ and LR-) of TVS, SIS and HS were calculated by comparison with the
      final pathological diagnosis. In addition, area under the curve (AUC) values were
      also calculated. RESULTS: Polypoid lesion was the most common abnormal pathology.
      LR+ and LR- of TVS, SIS, and HS were 3.13 and 0.15, 9.83 and 0.07, 13.7 and 0.02
      respectively in detection of any abnormal pathology, and the AUCs of TVS, SIS,
      and HS were 0.804, 0.920, and 0.954 respectively. When the three procedures were
      compared with each other separately, HS had the best diagnostic accuracy, and the
      diagnostic accuracy of HS and SIS was superior to TVS (p(1)=0.000, p(2)=0.000).
      For the detection of polypoid lesions, HS was the most accurate diagnostic
      procedure (AUC=0.947), followed by SIS (AUC=0.894) and TVS (AUC=0.778).
      CONCLUSION: HS provides the most accurate diagnosis and allows treatment in the
      same session in premenopausal women with abnormal uterine bleeding.

PMID- 22154670
TI  - [Single pregnancy outcome after blastocyst transfer: comparison with cleavage
      stage embryo transfers].
AB  - OBJECTIVES: It has been clearly shown that transfer of fresh blastocysts was
      efficient in in vitro fertilization cycles. However, only few data have been
      published about pregnancy outcome and health of children born. This study
      including only single pregnancies compared pregnancy, delivery and neonatal
      outcomes after blastocyst transfers in comparison with early cleavage stage
      embryo transfers (Day 2). PATIENTS AND METHODS: A retrospective study has been
      performed at the hospital of Tours from January 2002 to June 2009. Considering
      only primiparous women with similar ages, the outcome of 1574 single pregnancies
      issued from blastocyst transfers (n=588) or early cleavage stage transfers
      (n=959) has been compared. Data have been collected from FIVNAT forms, filled in
      by voluntary couples. RESULTS: The rate of return of FIVNAT forms was 97.6%. The
      pregnancy and delivery outcomes, sex ratio, birth weight, health of newborns were
      similar between both groups. DISCUSSION AND CONCLUSION: Regarding pregnancy,
      obstetric and delivery outcomes after blastocyst transfers, the literature data
      remain poor, much debated, and mixing often single and multiple pregnancies. The
      results of this study seem reassuring but have to be confirmed by further
      studies.

PMID- 22154671
TI  - [Is the socioeconomic deprivation EPICES score useful in obstetrics?].
AB  - OBJECTIVES: To describe a validated and multifactorial deprivation score to study
      the relationship between socioeconomic deprivation and perinatal risks. PATIENTS
      AND METHODS: The index of deprivation EPICES (Evaluation of Precarity and
      Inequalities in Health Examination Centers) was used to characterize the
      deprivation status of 234 women in post-partum in comparison with perinatal
      morbidity. The cutoff value of 30.7 was the threshold to define deprivation.
      RESULTS: Two hundred and eight patients were included in this retrospective study
      from whom 48 (23%) had a score of deprivation higher than 30.7. Maternofetal
      morbidity was more severe in deprived patients. DISCUSSION AND CONCLUSION: The
      current results show that the EPICES score could be a useful obstetrical tool for
      the identification of deprived women during pregnancy.

PMID- 22154672
TI  - [Outcome of embryo vitrification compared to slow freezing process at early
      cleavage stages. Report of the first French birth].
AB  - OBJECTIVES: Since the end of 2010, France by "l'Agence de Biomedecine" has
      validated the embryo vitrification procedure as an improvement of the slow
      freezing method. We presented here data concerning biological and clinical
      outcomes from a prospective observational study where early cleavage stage good
      quality embryos were vitrified and warmed. We compared these results to those of
      a retrospective series where embryos were thawed after a slow freezing procedure
      (SF). We report also the first French live birth following embryo vitrification.
      PATIENTS AND METHODS: In all, 58 cycles of frozen-thawed embryo transfers (FET)
      following vitrification were prospectively included and compared with 189 FET
      from SF method. Primary end points were the (i) survival rate (SR) (% of embryos
      with >=50% post-thaw intact blastomeres), (ii) intact survival rate (ISR) (% of
      embryos with 100% post-thaw intact blastomeres) and (iii) survival blastomeres
      index (SBI) (% of post thaw intact blastomeres per survival embryo). Secondary
      end point was the clinical pregnancy rate (CPR) defined as the presence of an
      intra-uterine gestational sac with positive foetal heart beat. We report here the
      first French live birth following embryo vitrification. RESULTS: In all, 87 and
      412 embryos have been thawed following vitrification and SF, respectively. We
      observed a highly significant increase of SR, ISR et SBI respectively when
      thawing concerned vitrified embryos rather than those from SF method (98.3+/
      13.1% vs. 77.3+/-32.0%, P<10(-4); 88.2+/-28.3% vs. 47.7+/-41.4%, P<10(-4); 97.7+/
      6.1% vs. 87.3+/-14.4%, P<10(-4)). Furthermore, CPR were of 32.7% (19/58) and of
      18.5% (35/189) following FET performed after vitrification or SF and thawing
      (P=0.03), respectively. The live birth of two healthy girls occurred following a
      caesarean section after 38 weeks of amenorrhea the 8th of August 2011. DISCUSSION
      AND CONCLUSION: We experienced in our study that the post-thaw survival of
      vitrified embryos was significantly better than those of embryos resulting from
      SF. Then, a better CPR per thawed embryo cycle was observed following
      vitrification.

PMID- 22154673
TI  - Evolution of the bomolochiform superfamily complex (Copepoda: Cyclopoida): new
      insights from ssrDNA and morphology, and origin of Umazuracolids from polychaete
      infesting ancestors rejected.
AB  - Poecilostome cyclopoids are among the most morphologically diverse copepods,
      having established symbiotic relationships with teleosts, elasmobranchs and
      invertebrate hosts belonging to no fewer than 14 marine phyla. Many parasitic
      lineages display radically divergent body plans and on that basis have
      traditionally been placed at higher taxonomic rank than they deserve. The most
      recent example is the monotypic family Umazuracolidae, established for a derived
      fish parasite with bomolochiform affinities. Phylogenetic analysis of complete
      ssrDNA (18S) sequences of 44 species belonging to 21 families of cyclopoid
      copepods shows that there is no support for the familial distinctiveness of the
      Umazuracolidae. Both maximum parsimony tree reconstruction and Bayesian
      inference, operating under the GTR+I+Gamma model of nucleotide substitution,
      unambiguously placed Umazuracola elongatus in the Taeniacanthidae within the
      predominantly fish parasitic bomolochiform complex, refuting the original
      suggestion of a shared most recent common ancestry with polychaete symbionts. The
      phylogenies also revealed that the bomolochiform families and the Clausidiidae
      (and allies) form a monophyletic group, the clausidiiform complex, with high
      nodal support under both methods. Bayesian inference suggested a diphyletic
      origin of the "Poecilostomatoida" with the clausidiiform family-group holding a
      basal position while the traditional cyclopoid families form a monophyletic group
      in apposition to a second poecilostomatoid clade; however, maximum parsimony
      results were equivocal, depending on outgroup selection. Scrutiny of the
      morphological characters diagnosing the monotypic families Tegobomolochidae and
      Tuccidae demonstrated that they merely represent derived lineages within more
      inclusive taxa, the former being related to a group of nostril-inhabiting genera
      within the Bomolochidae, the latter forming the sistergroup of Taeniacanthodes
      within the Taeniacanthidae. The taeniacanthid genus Makrostrotos occupies a
      position at the base of the bomolochiform complex and is fixed as the type of a
      new family, Makrostrotidae. Although both morphological and molecular evidence
      hint that the Bomolochidae is nested within a paraphyletic Taeniacanthidae, the
      status quo of maintaining both families is favoured here pending additional
      molecular data. The bomolochiform complex, comprising the Bomolochidae,
      Taeniacanthidae, Telsidae and Makrostrotidae, is attributed superfamilial rank as
      the Bomolochoidea. A recent controversial phylogenetic analysis of the
      poecilostomatoid families is shown to be flawed, being based on a dataset
      containing imperfect or misleading information, and characters whose states were
      wrongly assessed.

PMID- 22154674
TI  - Detection of 10 medically important Candida species by seminested polymerase
      chain reaction.
AB  - A seminested PCR detecting ten medically important Candida species were achieved.
      Analytical sensitivity and specificity were not compromised.

PMID- 22154675
TI  - Antimicrobial resistance of Moraxella catarrhalis isolates in Taiwan.
AB  - BACKGROUND/PURPOSE: The prevalence of ampicillin-resistant Moraxella catarrhalis
      has been higher in Taiwan than in other countries, with reports of 97.7% in the
      1990s. The aims of this study were to assess resistance trends for M.
      catarrhalis, which causes respiratory tract infections, against several classes
      of oral antibiotics and to compare the minimum inhibitory concentration (MIC) of
      antimicrobial agents against M. catarrhalis isolates between 1993-1994 and 2001
      2004. METHODS: Clinical isolates of M. catarrhalis (n = 314) were collected from
      11 large medical centers in Taiwan between 2001 and 2004. beta-Lactamase
      production tests were performed. The MICs for 13 different oral antibiotics were
      calculated using the agar dilution method. Pulsed-field gel electrophoresis
      (PFGE) was performed for 18 randomly selected high-level ampicillin-resistant
      (BRO-1 beta-lactamase-positive, MIC >= 32 MUg/mL) isolates to investigate their
      genetic relatedness. RESULTS: The overall rate of beta-lactamase-producing
      isolates was 97.8% (307/314). All isolates were susceptible to amoxicillin +
      clavulanate, chloramphenicol, cefixime, ciprofloxacin, erythromycin,
      levofloxacin, moxifloxacin, and roxithromycin. The rate of resistance to cefaclor
      and cefuroxime was 8.3% and 1.3%, respectively, while no resistance was found in
      1993-1994. Resistance to trimethoprim-sulfamethoxazole (SXT) and tetracycline was
      18.5% and 19.8%, respectively. Comparison of 1993-1994 and 2001-2004 isolates
      revealed that the zone diameter for amoxicillin + clavulanate disks decreased
      from 43 mm in 1993-1994 to 32 mm in 2001-2004 (p < 0.001). However, MIC(50) (0.25
      MUg/mL in both 1993-1994 and 2001-2004) and MIC(90) (0.5 MUg/mL in both 1993-1994
      and 2001-2004) for amoxicillin + clavulanate did not differ between the study
      periods. The PFGE typing results demonstrate that at least two closely related
      BRO-1 clones are spreading in Taiwan. CONCLUSION: The rates of resistance to
      cefaclor, cefuroxime, tetracycline and SXT are now increasing in Taiwan.
      Molecular typing showed that at least two closely related BRO-1 clones are
      circulating. Although amoxicillin + clavulanate remains the antimicrobial therapy
      of choice for M. catarrhalis infections, continued surveillance of antimicrobial
      susceptibility and application of control measures against further transmission
      are required to inhibit the emergence of the resistant strains.

PMID- 22154676
TI  - Clinical characteristics and treatment outcomes of patients with tubo-ovarian
      abscess at a tertiary care hospital in Northern Taiwan.
AB  - BACKGROUND/PURPOSE: Controversy exists regarding the need for surgical
      intervention in patients with tubo-ovarian abscess (TOA). This study was aimed at
      investigating the clinical characteristics and treatment outcomes in patients
      with TOA at a tertiary care hospital in Taiwan. METHODS: The medical records of
      83 patients who presented at the hospital with TOA between January 1, 2006, and
      December 31, 2007, were retrospectively reviewed. Outcomes of patients who
      received medical treatment alone or underwent surgical intervention were analyzed
      using univariate and logistic regression analyses. RESULTS: Among the 83 patients
      with TOA, 13 patients (15.7%) underwent surgical intervention, and 70 patients
      (84.3%) received medical treatment alone. Significant variables related to
      surgical treatment in the univariate analysis were length of stay (short vs.
      long; t = -2.267, p = 0.026), department of admission (emergency room vs.
      outpatient department; chi(2) = 7.459, p = 0.006), number of live births
      (nulliparous vs. multiparous; chi(2) = 18.202, p = 0.001), and C-reactive protein
      (CRP) level (high vs. low; t = -2.250, p = 0.028). Logistic regression analysis
      performed to determine influential factors for surgical treatment showed that the
      operation odds ratio of three to four live births versus no live births was
      33.995 (p = 0.043) and that of two live births versus no live births was 13.598
      (p = 0.026). CONCLUSION: Patients with TOA who underwent surgery had a longer
      duration of hospitalization. Among the patients who underwent surgical
      intervention, those admitted to the emergency room had higher CRP levels and were
      more likely to be multiparous.

PMID- 22154677
TI  - Shewanella putrefaciens, a rare cause of splenic abscess.
AB  - Splenic abscess is uncommon and is still associated with significant morbidity
      and mortality. Gram-negative bacilli are the most commonly isolated organisms,
      followed by Gram-positive cocci. However, the predominant organisms found depend
      on the geographic location. Shewanella putrefaciens is a Gram-negative non
      fermentative oxidative bacillus found in the environment. Infection usually
      manifests with a number of clinical syndromes, most commonly as skin or soft
      tissue infections, typically in patients whose immune system is compromised.
      Intra-abdominal abscess is extremely rare. We report a case of a 22-year-old
      female who presented with S. putrefaciens splenic abscesses as the first
      manifestation of diabetes mellitus, which was successfully managed with a course
      of antibiotic therapy.

PMID- 22154678
TI  - Clonal spread of multidrug-resistant Acinetobacter baumannii in eastern Taiwan.
AB  - BACKGROUND AND PURPOSE: This study was conducted to investigate the molecular
      epidemiology and antimicrobial susceptibility of multidrug-resistant (MDR)
      Acinetobacter baumannii to three types of antibiotics. METHODS: One hundred and
      thirty-four specimens of MDR A baumannii were collected from three branches
      (Taipei, Dalin, and Hualien branches) of Buddhist Tzu Chi Hospital, which are
      located in northern, southern, and eastern Taiwan, during 2007. Genotyping was
      performed by pulsed-field gel electrophoresis. Antibiotic susceptibilities to
      colistin, rifampicin, and tigecycline were determined. The synergistic effects of
      rifampin and colistin were also evaluated. RESULTS: Antibiotic susceptibility
      testing showed that 10.4%, 47.8% and 45.5% of the MDR A baumannii isolates are
      resistant to colistin, rifampicin, and tigecycline, respectively. A majority of
      the rifampicin-resistant isolates (62.7%) were found in the Haulien branch,
      whereas 62.2% of tigecycline-resistant isolates were found in the Taipei branch.
      The combination of colistin and rifampicin had a synergistic effect on all of the
      isolates. Genotyping by pulsed-field gel electrophoresis identified 17, 23, and
      11 pulsotypes in the Taipei, Dalin, and Haulien branches, respectively.
      Furthermore, 74.5% of isolates in the Haulien branch were identified as one of
      three pulsotypes. Among 37 rifampicin-resistant and 22 tigecycline-resistant MDR
      A baumannii isolates found in the Haulien branch, 51.3% (19/37) and 50% (11/22)
      of the isolates belonged to the same clone, respectively. CONCLUSION: This study
      confirms the high prevalence of resistance to rifampicin and tigecycline in MDR A
      baumannii in the three hospitals that were studied, and the high proportion of
      identical strains that exist in eastern Taiwan.

PMID- 22154679
TI  - Association between polymorphism of methylenetetrahydrofolate reductase (MTHFR)
      C677T and risk of myocardial infarction: a meta-analysis for 8,140 cases and
      10,522 controls.
AB  - BACKGROUND AND AIMS: The methylenetetrahydrofolate reductase (MTHFR) gene C677T
      polymorphism has been reported to be associated with myocardial infarction (MI),
      but results from previous studies are conflicting. The present study aimed at
      investigating the association between this polymorphism and risk of MI using a
      meta-analysis on the published studies. METHODS: Medline, EBSCO, BIOSIS, and
      Cochrane Library were searched to identify eligible studies published in English
      before August, 2011. Data were extracted using standardized methods. The
      association was assessed by odds ratio (OR) with 95% confidence intervals (CI).
      Begg's test was used to measure publication bias. RESULTS: A total of 30 case
      control studies containing 8,140 MI cases and 10,522 controls were involved in
      this meta-analysis. Overall, significant association was found between MTHFR
      C677T polymorphism and risk of MI when all studies pooled with fixed-effects
      model for TT vs. CT (OR = 1.183, 95% CI: 1.076-1.300). In the subgroup analysis,
      the same association was found in overall Caucasians (OR = 1.139, 95% CI: 1.007
      1.288) and young/middle-aged (<50 years) Caucasians (OR = 1.275, 95% CI: 1.077
      1.509). No associations were detected between MTHFR C677T and the risk of MI in
      elderly male or female Caucasians, East Asians, South Asians, and African
      Americans. CONCLUSIONS: Meta-analysis results suggest that the MTHFR C677T
      polymorphism was associated with risk of MI in young/middle-aged Caucasians. The
      effect of the variants on the expression levels and the possible functional role
      of the variants in MI should be addressed in further studies.

PMID- 22154680
TI  - Association between MMP2-1306C/T polymorphism and digestive cancer risk: need for
      clarification of data in a recent meta-analysis.

PMID- 22154682
TI  - Early cataract formation due to galactokinase deficiency: impact of newborn
      screening.
AB  - BACKGROUND AND AIMS: Galactokinase (GALK) deficiency is an autosomal recessive
      disorder causing cataract formation that can be prevented or mitigated by early
      diagnosis and galactose-restricted diet. The aim of this retrospective study was
      to explore whether GALK-deficiency meets the criteria for neonatal mass screening
      programs. METHODS: From 2000 until 2010, the Screening Laboratory Hannover
      performed newborn screening in 1,950,927 infants from Germany for galactosemia by
      measuring galactose-1-phosphate-uridyl-transferase and total galactose
      concentration (free galactose plus galactose-1-phosphate), including automatic
      screening for GALK deficiency. RESULTS: Eleven cases were found with elevated
      galactose levels accompanied by normal transferase activity. Nine of 11 cases
      were informative; the diagnosis was established by demonstrating deficient
      activity of the GALK enzyme in erythrocytes. To our knowledge, screening did not
      produce any false negative results. All patients were treated with a galactose
      restricted diet from the neonatal period or infancy. Three of nine patients
      suffered from congenital cataracts or eventual development of cataracts, despite
      normal galactose concentrations in blood. CONCLUSIONS: Newborn screening for GALK
      deficiency prevents or at least mitigates cataract formation. As screening for
      GALK deficiency is technically simple, it seems to be reasonable to include this
      disorder in routine screening programs by simultaneous determination of
      transferase activity and quantification of galactose plus galactose-1-phosphate
      in dried blood spots.

PMID- 22154683
TI  - Immunomodulatory activities of chitin microparticles on Leishmania major-infected
      murine macrophages.
AB  - BACKGROUND: Chitin microparticles (CMPs) are found to be potent macrophage
      stimulators; however, their immunomodulatory effects on the parasite-infected
      macrophages have not yet been studied. To address this issue, we used a
      Leishmania major-infected murine macrophage model and characterized the
      regulatory effects of CMPs on the parasite-infected cells. METHODS: Mouse
      peritoneal macrophages were prepared and infected with L. major (MRHO/IR/1975/ER)
      standard strain. Following cell treatment with CMPs (500 MUg/mL) for 48 h,
      percent of infected macrophages was determined by Giemsa staining and compared
      with untreated cells. To find the potential mechanisms of the activity of CMPs,
      TNF-alpha and accumulated nitrite in the culture supernatants of the treated and
      untreated cells were also measured by ELISA and colorimetric Griess assays,
      respectively. RESULTS: According to the obtained results, chitin microparticles
      reduced the ex vivo parasite infectivity by ~12%. However, this inhibitory effect
      was not directly related to the increased biosynthesis and release of nitric
      oxide (NO) by macrophages. Instead, we observed a significant increase in the
      level of TNF-alpha secretion due to cell treatment with CMPs. Interestingly, this
      overexpression of TNF-alpha did not impair cell viability, suggesting the anti
      apoptotic effects of the CMPs. CONCLUSIONS: These findings show that chitin
      microparticles have immunomodulatory effects on L. major-infected macrophages and
      further provide motivations for future studies on their in vivo effects.

PMID- 22154684
TI  - Short echo time in vivo prostate 1H-MRSI.
AB  - Visualization of short echo time (TE) metabolites in prostate magnetic resonance
      spectroscopic imaging is difficult due to lipid contamination and pulse timing
      constraints. In this work, we present a modified pulse sequence to permit short
      echo time (TE=40ms) acquisitions with reduced lipid contamination for the
      detection of short TE metabolites. The modified pulse sequence employs the
      conformal voxel MRS (CV-MRS) technique, which automatically optimizes the
      placement of spatial saturation planes to adapt the excitation volume to the
      shape of the prostate, thus reducing lipid contamination in prostate magnetic
      resonance spectroscopic imaging (MRSI). Metabolites were measured and assessed
      using a modified version of LCModel for analysis of in vivo prostate spectra. We
      demonstrate the feasibility of acquiring high quality spectra at short TEs, and
      show the measurement of short TE metabolites, myo-inositol, scyllo-inositol,
      taurine and glutamine/glutamate for both single and multi-voxel acquisitions. In
      single voxels experiments, the reduction in TE resulted in 57% improvement in the
      signal-to-noise ratio (SNR). Additional 3D MRSI experiments comparing short
      (TE=40 ms), and long (TE=130 ms) TE acquisitions revealed a 35% improvement in
      the number of adequately fitted metabolite peaks (775 voxels over all subjects).
      This resulted in a 42 +/- 24% relative improvement in the number of voxels with
      detectable citrate that were well-fitted using LCmodel. In this study, we
      demonstrate that high quality prostate spectra can be obtained by reducing the TE
      to 40 ms to detect short T2 metabolites, while maintaining positive signal
      intensity of the spin-coupled citrate multiplet and managing lipid suppression.

PMID- 22154685
TI  - Preclinical evaluation of [11C]NE40, a type 2 cannabinoid receptor PET tracer.
AB  - INTRODUCTION: Up-regulation of the type 2 cannabinoid receptor (CB(2)R) has been
      reported in (neuro)inflammatory diseases. In this study, we report the
      preclinical evaluation of [(11)C]NE40 as positron emission tomography (PET)
      radioligand for visualization of the CB(2)R. METHODS: The selectivity of NE40 for
      CB(2)R and its toxicity and mutagenicity were determined. [(11)C]NE40 was
      evaluated by biodistribution and autoradiography studies in normal rats and a
      microPET study in normal mice, rats and a rhesus monkey. Specific in vivo binding
      of [(11)C]NE40 to human CB(2)R (hCB(2)R) was studied in a rat model with hCB(2)R
      overexpression. RESULTS: [(11)C]NE40 shows specific CB(2)R binding in the spleen
      and blood of normal rats and high brain uptake in rhesus monkey. [(11)C]NE40
      showed specific and reversible binding to hCB(2)R in vivo in a rat model with
      local hCB(2)R overexpression. CONCLUSIONS: [(11)C]NE40 shows favorable
      characteristics as radioligand for in vivo visualization of the CB(2)R and is a
      promising candidate for hCB(2)R PET imaging.

PMID- 22154686
TI  - Dosimetry of 99mTc-HMPAO in mesenchymal stem cells.

PMID- 22154687
TI  - Difficulties in dopamine transporter radioligand PET analysis: the example of LBT
      999 using [18F] and [11C] labelling: part II: Metabolism studies.
AB  - INTRODUCTION: LBT-999, (E)-N-(4-fluorobut-2-enyl)-2beta-carbomethoxy-3beta-(4'
      tolyl)nortropane, has been developed for PET imaging of the dopamine transporter.
      [(18)F]LBT-999 PET studies in baboons showed a lower brain uptake than [(11)C]LBT
      999 and a high bone uptake, suggesting the presence of interfering metabolites.
      Therefore, in vitro and in vivo metabolism of these radiotracers was
      investigated. METHODS: Rat and human liver microsomal incubations, baboon plasma
      and rat brain extracts were analyzed by radio-HPLC and LC-MS-MS. RESULTS: In
      vitro experiments demonstrated the formation by P450s of five polar metabolites.
      The main routes of LBT-999 metabolism proposed were N-dealkylation, tolyl
      hydroxylation and dealkylation plus tolyl-hydroxylation. In vivo in baboons,
      [(18)F]LBT-999 was rapidly converted into a [(18)F]hydroxylated metabolite likely
      oxidized in plasma into a [(18)F]carboxylic acid and into unlabeled N-dealkyl-LBT
      999. The latter was detected in baboon plasma and in rat brain by LC-MS-MS. The
      time course of unchanged [(18)F]LBT-999 decreased rapidly in plasma and was
      higher than that of [(11)C]LBT-999 due to the formation of unlabeled N-dealkyl
      LBT-999. In rats, striatum-to-cerebellum ratios of [(18)F]LBT-999,
      [(18)F]hydroxylated and [(18)F]acidic metabolite were 20, 4.2 and 1.65,
      respectively, suggesting a possible accumulation of the hydroxylated compound in
      the striatum. CONCLUSION: P450s catalyzed the formation of dealkylated and
      hydroxylated metabolites of LBT-999. In baboons, an extensive metabolism of
      [(18)F]LBT-999, with formation of unlabeled N-dealkyl-LBT-999,
      [(18)F]fluorobutenaldehyde (or its oxidation product) and [(18)F]hydroxy-LBT-999
      able to penetrate the brain, prevented an easy and accurate estimation of the
      input function of the radiotracer. CYP3A4 being the main P450 involved in the
      metabolism of LBT-999, a similar pathway may occur in humans and confound PET
      quantification.

PMID- 22154688
TI  - Review: The placenta and developmental programming: balancing fetal nutrient
      demands with maternal resource allocation.
AB  - The placenta evolved to support development of the fetus, and so potentially
      plays a key role in the aetiology of developmental programming through its impact
      on nutrient transfer. Placental transport efficiency depends on a variety of
      parameters, including surface area for exchange, thickness of the interhaemal
      membrane and density of transporter proteins inserted into the trophoblast
      membranes. Here, we review recent studies that tested whether adaptations of
      placental efficiency are induced in the mouse placenta when maternal nutrient
      supply and fetal demand are manipulated experimentally. Naturally small
      placentas, and those exposed to maternal undernutrition, displayed structural
      changes indicative of accelerated maturation at E16, with enlargement of the
      labyrinth exchange zone at the expense of the endocrine junctional zone. These
      changes were associated with increased transport of a non-metabolisable amino
      acid analogue per gram of placenta, and expression of genes encoding specific
      System A transporters. Up-regulation of transporters was also observed when a
      mismatch between placental size and fetal demand was generated through genetic
      manipulation of the Igf2/H19 axis. Conversely, overgrowth of the placenta induced
      by deletion of H19 resulted in reduced transport capacity and expression of
      transporter genes. We conclude that under conditions when the maternal nutrient
      supply or placental size may be limiting for normal fetal growth, the placenta
      adapts so as to increase its transport capacity. Hence, it ameliorates the
      effects of environmental cues that would otherwise lead to more extensive
      developmental programming. The P0 transcript of Igf2 appears to be a strong
      candidate as a mediator of these adaptations in the mouse.

PMID- 22154689
TI  - Ontogeny of growth-regulating genes in the placenta.
AB  - BACKGROUND: Placental nutrient flow is the primary determinant of fetal growth.
      This key function of the placenta depends on several growth-promoting or 
      suppressing imprinted genes including Insulin-like growth factor [IGF] axis
      genes, which regulate nutrient transfer across the placenta. However whether
      changes in the placental expression of these genes parallel increased fetal
      growth observed in the second and third trimester remains unknown. OBJECTIVE: The
      aim of our study was to determine the ontogeny of key IGF axis genes and other
      growth regulating imprinted genes in the placenta and to characterize patterns of
      placental gene expression associated with intrauterine growth restriction (IUGR).
      STUDY DESIGN: Real time RT-PCR analysis of 11 genes using specific probes were
      performed in the placental tissue collected at the time of delivery from 63
      subjects with live birth pregnancies from 24 to 40 weeks gestation between 2009 
      2010. RESULTS: We found that paternally expressed gene ZNF127 (p < 0.001) was
      upregulated whereas IGF1 (p = 0.001) and maternally expressed gene PHLDA2 (p =
      0.001) were downregulated with advancing gestational age. ROC analysis revealed a
      significant change in the expression of the above genes early in the third
      trimester. When compared to age-matched appropriate for gestational age (AGA)
      infants, expression of PHLDA2 (p = 0.03) IGF2R (p < 0.05) was upregulated in IUGR
      infants. Maternal age was also a significant predictor for IUGR (p = 0.05).
      CONCLUSION: We found increased placental expression of growth-promoting imprinted
      genes and decreased expression of growth-suppressive imprinted genes with
      advancing gestational age. These changes in placental gene expression could
      potentially explain accelerated fetal growth seen in the third trimester.
      Upregulation of maternally expressed imprinted genes in IUGR population supports
      the "parental conflict hypothesis".

PMID- 22154690
TI  - Cryopreservation of placental biopsies for mitochondrial respiratory analysis.
AB  - Mitochondrial function is required to support energetically-demanding processes
      in the placenta. As such, a compromise in mitochondrial function could severely
      impact fetal growth and development. Respirometry is a highly useful method for
      studying mitochondrial function, but is not possible in freeze-thawed
      mitochondria, which become uncoupled. We have developed a novel method that
      permits respiratory analysis of cryopreserved placental tissue. We studied
      mitochondrial function in 7 normal human placentas, analysing both fresh and
      cryopreserved samples. We found no impairments in respiration following
      cryopreservation in the delivery suite, with enhanced coupling, as indicated by
      higher respiratory control ratios, than in fresh placental samples transported to
      the laboratory on ice.

PMID- 22154691
TI  - IFPA Meeting 2011 workshop report I: Placenta: Predicting future health; roles of
      lipids in the growth and development of feto-placental unit; placental nutrient
      sensing; placental research to solve clinical problems--a translational approach.
AB  - Workshops are an important part of the IFPA annual meeting as they allow for
      discussion of specialized topics. At IFPA meeting 2011 there were twelve themed
      workshops, four of which are summarized in this report. These workshops related
      to both basic science and clinical research into placental growth and nutrient
      sensing and were divided into 1) placenta: predicting future health; 2) roles of
      lipids in the growth and development of feto-placental unit; 3) placental
      nutrient sensing; 4) placental research to solve clinical problems: a
      translational approach.

PMID- 22154692
TI  - Decreasing maternal nutrient intake during the final third of pregnancy in
      previously overnourished adolescent sheep: effects on maternal nutrient
      partitioning and feto-placental development.
AB  - When pregnant adolescent sheep are overnourished during pregnancy normal nutrient
      partitioning priorities to the gravid uterus are altered, leading to impaired
      placental development and fetal growth restriction. We hypothesized that
      decreasing dietary intake in overnourished dams during the final third of
      gestation may reverse this inappropriate nutrient partitioning in favor of the
      fetus. Adolescent ewes were offered control (C; n = 12) or high (H; n = 20)
      dietary intakes to induce normal vs. compromised placental development. Ten ewes
      receiving the H intake were switched to a low intake at d90 of gestation (HL).
      Between d90 to 130, HL dams lost weight and adiposity, and metabolic hormones and
      glucose at d130 were less than H and similar to C. In spite of these maternal
      changes, at d130 fetal bodyweight was equivalent in HL and H groups and ~20% less
      than in C. A greater degree of brain sparing was evident in HL fetuses and
      glucose and insulin concentrations were more perturbed than in H fetuses.
      Relative to C, placentome weight was reduced by 46 and 32% in H and HL and the
      fetal:placentome weight ratio was H > HL > C. Placental vascular morphology was
      largely unaffected by maternal diet during late gestation but mRNA expression of
      five angiogenic genes was up-regulated in the fetal cotyledon of HL pregnancies,
      commensurate with blood vessel remodeling. Nevertheless, overfeeding to promote
      maternal anabolic growth during adolescent pregnancy impairs feto-placental
      development that cannot be rescued by reducing maternal intake during the final
      third of gestation.

PMID- 22154694
TI  - Pulmonary mechanics during mechanical ventilation.
AB  - The use of mechanical ventilation has become widespread in the management of
      hypoxic respiratory failure. Investigations of pulmonary mechanics in this
      clinical scenario have demonstrated that there are significant differences in
      compliance, resistance and gas flow when compared with normal subjects. This
      paper will review the mechanisms by which pulmonary mechanics are assessed in
      mechanically ventilated patients and will review how the data can be used for
      investigative research purposes as well as to inform rational ventilator
      management.

PMID- 22154693
TI  - Persistence of the nasotrigeminal reflex after pontomedullary transection.
AB  - Most behaviors have numerous components based on reflexes, but the neural
      circuits driving most reflexes rarely are documented. The nasotrigeminal reflex
      induced by stimulating the nasal mucosa causes an apnea, a bradycardia, and
      variable changes in mean arterial blood pressure (MABP). In this study we tested
      the nasotrigeminal reflex after transecting the brainstem at the pontomedullary
      junction. The nasal mucosae of anesthetized rats were stimulated with ammonia
      vapors and their brainstems then were transected. Complete transections alone
      induced an increase in resting heart rate (HR; p<0.001) and MABP (p<0.001), but
      no significant change in ventilation. However, the responses to nasal stimulation
      after transection were similar to those seen prior to transection. HR still
      dropped significantly (p<0.001), duration of apnea remained the same, as did
      changes in MABP. Results from rats whose transection were incomplete are
      discussed. These data implicate that the neuronal circuitry driving the
      nasotrigeminal reflex, and indirectly the diving response, is intrinsic to the
      medulla and spinal cord.

PMID- 22154695
TI  - The effect of baseline metabolic rate on pulmonary O2 uptake kinetics during very
      heavy intensity exercise in boys and men.
AB  - This study tested the hypothesis that pulmonary VO2 kinetics would be slowed
      during 'work-to-work' exercise in adults but not in children. Eight boys (mean
      age=12.5 +/- 0.5 years) and nine men completed very heavy step transitions
      initiated from either 'unloaded' pedalling (U->VH) or unloaded-to-moderate
      cycling (i.e. U->M to M->VH). The phase II tau was significantly (p<0.05)
      lengthened in M->VH compared to U->M and U->VH in boys (30 +/- 5 vs. 19 +/- 5 vs.
      21 +/- 5 s) and men (49 +/- 14 vs. 30 +/- 5 vs. 34 +/- 8 s). In U->VH, a greater
      relative VO2 slow component temporally coincided with an increased linear iEMG
      slope in men compared boys (VO2 slow component: 16 +/- 3 vs. 11 +/- 4%; iEMG
      slope: 0.19 +/- 0.24 vs. -0.06 +/- 0.14%, p<0.05). These results suggest that an
      age-linked modulation of VO2 kinetics might be influenced by alterations in
      muscle fibre recruitment following the onset of exercise.

PMID- 22154696
TI  - Mapping in vivo signal transduction defects by phosphoproteomics.
AB  - Abnormal protein phosphorylation is implicated in a variety of diseases, but
      until recently the complexity of tissue material, technical limitations, and the
      substantial volume of required data processing did not allow large-scale
      phosphoproteomic analysis of patient material, despite tremendous progress in
      developing mass spectrometry technologies. Phosphoproteomic approaches were
      primarily developed using model systems such as transformed cell lines, but
      technological advances in proteomics now make it feasible to analyze thousands of
      phosphorylation sites in a quantitative manner in patient materials or complex
      animal and cellular model systems to identify signaling abnormalities. This
      review summarizes very recent phosphoproteomic studies on complex tissue
      material, including tissue samples in biobanks, to complement recent reviews that
      focus primarily on technical advances in instrumentation and methods. Several
      successful examples reviewed here suggest it is now possible to apply
      phosphoproteomic techniques to address more challenging medical questions such as
      mapping within patient samples signal transduction defects that are relevant for
      diagnosis and individualized treatment development.

PMID- 22154698
TI  - Rheumatoid arthritis, alveolar echinococcosis, and rituximab: a case report.

PMID- 22154700
TI  - Premature epiphyseal closure in an adolescent treated by retinoids for acne: an
      unusual cause of anterior knee pain.
AB  - Retinoids are effective and widely prescribed in the treatment of severe acne.
      However their use can be associated with numerous side effects. Some rare cases
      of premature epiphyseal closure were reported. We present the case of a sixteen
      year-old soccer player referred for progressive anterior pain in both knees,
      evoking a patellar problem. Careful pharmacological questioning revealed use of
      isotretinoin for several months. MRI findings showed an irregularity of the
      growth plate and an important metaphyso-epiphyseal oedema, more noticeable in the
      left knee. Retinoid-induced premature epiphyseal closure was diagnosed. The
      treatment was stopped, with a resolution of pain within two months. After
      recovery a persisting small sequelar thumbprint-like growth plate lesion was
      observed on the control MRI. Retinoids induce an invasion of the growth plate by
      osteoclasts and a decrease in proteoglycans synthesis. It seems that the knee is
      the most affected joint. This complication being rare, a radiological follow-up
      of the young patients treated by retinoids is not proposed.

PMID- 22154697
TI  - p21, an important mediator of quiescence during pituitary tumor formation, is
      dispensable for normal pituitary development during embryogenesis.
AB  - A delicate balance between proliferation and differentiation must be maintained
      in the developing pituitary to ensure the formation of the appropriate number of
      hormone producing cells. In the adult, proliferation is actively restrained to
      prevent tumor formation. The cyclin dependent kinase inhibitors (CDKIs) of the
      CIP/KIP family, p21, p27 and p57, mediate cell cycle inhibition. Although p21 is
      induced in the pituitary upon loss of Notch signaling or initiation of tumor
      formation to halt cell cycle progression, its role in normal pituitary
      organogenesis has not been explored. In wildtype pituitaries, expression of p21
      is limited to a subset of cells embryonically as well as during the postnatal
      proliferative phase. Mice lacking p21 do not have altered cell proliferation
      during early embryogenesis, but do show a slight delay in separation of
      proliferating progenitors from the oral ectoderm. By embryonic day 16.5, p21
      mutants have an alteration in the spatial distribution of proliferating pituitary
      progenitors, however there is no overall change in proliferation. At postnatal
      day 21, there appears to be no change in proliferation, as assessed by cells
      expressing Ki67 protein. However, p21 mutant pituitaries have significantly less
      mRNA of Myc and the cyclins Ccnb1, Ccnd1, Ccnd2 and Ccne1 than wildtype
      pituitaries. Interestingly, unlike the redundant role in cell cycle inhibition
      uncovered in p27/p57 double mutants, the pituitary of p21/p27 double mutants has
      a similar proliferation profile to p27 single mutants at the time points
      examined. Taken together, these studies demonstrate that unlike p27 or p57, p21
      does not play a major role in control of progenitor proliferation in the
      developing pituitary. However, p21 may be required to maintain normal levels of
      cell cycle components.

PMID- 22154701
TI  - Interferon-alpha as a treatment target in systemic lupus erythematosus.

PMID- 22154702
TI  - Singularities, odds ratios, and significance: California emergency department
      closures and Los Angeles.

PMID- 22154703
TI  - Is there a blood test that can rule out serious bacterial infection in children?

PMID- 22154704
TI  - Effects of risperidone treatment in adolescence on hippocampal neurogenesis,
      parvalbumin expression, and vascularization following prenatal immune activation
      in rats.
AB  - Maternal infection in pregnancy is an environmental risk factor for the
      development of schizophrenia and related disorders in the offspring, and this
      association is recapitulated in animal models using gestational infection or
      immune stimulation. We have recently shown that behavioral abnormalities and
      altered hippocampal morphology emerging in adult offspring of dams treated with
      the viral mimic polyriboinosinic-polyribocytidilic acid (poly I:C) are prevented
      by treatment with the atypical antipsychotic drug risperidone (RIS) in
      adolescence. Here we used a battery of cellular markers and Nissl stain to
      morphometrically analyze different hippocampal cell populations in the offspring
      of poly I:C and saline-treated mothers that received saline or RIS in
      adolescence, at different time points of postnatal development. We report that
      impaired neurogenesis, disturbed micro-vascularization and loss of parvalbumin
      expressing hippocampal interneurons, are found in the offspring of poly I:C
      treated dams. Most, but not all, of these neuropathological changes are not
      present in poly I:C offspring that had been treated with RIS. These effects may
      be part of the complex processes underlying the capacity of RIS treatment in
      adolescence to prevent structural and behavioral abnormalities deficits in the
      poly I:C offspring.

PMID- 22154705
TI  - Targeted gripping reduces shoulder muscle activity and variability.
AB  - The purpose of this study was to determine if the effect of visually targeted
      gripping on shoulder muscle activity was maintained with repeated exposures.
      Eleven healthy males had eight shoulder muscles monitored via surface
      electromyography while maintaining shoulder elevation at 90 degrees  in the
      scapular plane with and without a 30% grip force. Three non-gripping trials were
      followed by 15 gripping trials and another 3 non-gripping control trials.
      Gripping significantly decreased the activity of the anterior deltoid, trapezius,
      and latissimus dorsi over the exposure of 15 trials. Gripping also reduced
      variability in all muscles' activity. The changes in shoulder muscle activity are
      likely in response to forces being transferred through multi-articular muscles
      spanning from the forearm to the shoulder. Targeted gripping during shoulder
      elevation resulted in small but significant decreases in muscle activity and
      reduced variability which supports previous evidence for increased risk of upper
      extremity disorders in occupational settings.

PMID- 22154706
TI  - Humanistic and economic burden of generalized anxiety disorder in North America
      and Europe.
AB  - BACKGROUND: To review the humanistic and economic burden of generalized anxiety
      disorder (GAD). METHODS: MEDLINE, EMBASE and the Cochrane Library, limited to
      articles published in English, between 1987 and 2010, in North America, Europe
      and Australia. The key focus was humanistic or functional outcomes, cost of
      illness and economic outcomes. Ninety articles fitting criteria on (a) GAD study
      population, (b) United States, Europe or Australia, and (c) humanistic burden or
      economic burden were reviewed. Methods and findings were summarized by two
      researchers; inconsistencies were resolved by a third reviewer. RESULTS: GAD was
      associated with increased impairments in psychosocial functioning, role
      functioning, work productivity and health-related quality of life (HRQL). The
      HRQL impairments were comparable with those associated with depression or panic
      disorder. Patients with GAD and co-morbid depression reported significantly
      greater impairment in HRQL than did those with either disorder alone. GAD
      patients had significantly higher median medical costs than primary care patients
      without GAD (US $2375 versus $1448). The mean annual medical cost of GAD was
      $2138 higher than for other anxiety disorders (mean $6475). Finally, GAD was
      frequently under-recognized in primary care, and available studies reported that
      only 20% to 32% of patients were adequately treated. LIMITATIONS: The review was
      limited to pharmacologic treatments for GAD and to publications in English.
      CONCLUSIONS: GAD is associated with significant burden on patient functioning and
      well-being, leading to increased health care utilization and medical costs.
      Patients with GAD are often suboptimally treated, which adds to the HRQL burden
      of this disorder.

PMID- 22154707
TI  - Grief and physical health outcomes in U.S. soldiers returning from combat.
AB  - BACKGROUND: Few studies have measured the burden of physical health problems
      after Iraq/Afghanistan deployment, except in association with post-traumatic
      stress disorder (PTSD) or mild traumatic brain injury (mTBI). Grief, a correlate
      of health problems in the general population, has not been systematically
      examined. We aimed to identify the prevalence of post-deployment physical health
      problems and their association with difficulty coping with grief. METHODS:
      Infantry soldiers (n=1522) completed anonymous surveys using validated
      instruments six months following deployment in November-December 2008. Multiple
      logistic regression was used to assess the association of difficulty coping with
      grief and physical health. RESULTS: The most frequent physical health symptoms
      reported were: sleep problems (32.8%), musculoskeletal pain (32.7%), fatigue
      (32.3%), and back pain (28.1%). Difficulty coping with grief over the death of
      someone close affected 21.3%. There was a dose-response relationship between
      level of difficulty coping with grief and principal physical health outcomes
      (ps<.002). Controlling for demographics, combat experiences, injuries, PTSD,
      depression, and other factors, grief significantly and uniquely contributed to a
      high somatic symptom score (adjusted odds ratio (AOR)=3.6), poor general health
      (AOR=2.0), missed work (AOR=1.7), medical utilization (AOR=1.5), difficulty
      carrying a heavy load (AOR=1.7), and difficulty performing physical training
      (AOR=1.6; all 95% confidence intervals>1). LIMITATIONS: Data are cross-sectional
      and grief was measured with one item. CONCLUSIONS: Over 20% of soldiers reported
      difficulty coping with grief. This difficulty was significantly associated with
      physical health outcomes and occupational impairment. Clinicians should be aware
      of the unique role grief plays in post-deployment physical health when treating
      patients.

PMID- 22154708
TI  - Acquired lithium resistance revisited: discontinuation-induced refractoriness
      versus tolerance.
AB  - BACKGROUND: While some patients fail to respond to lithium from the outset,
      others are initially responsive and then develop treatment resistance. These
      acquired forms of lithium resistance have received relatively little clinical
      attention. METHODS: We review the literature on the two different forms of
      acquired treatment resistance lithium that occur following an initial good
      response to lithium-discontinuation-induced refractoriness and tolerance- and
      discuss the possible neurobiological mechanisms involved. RESULTS: Multiple
      investigators have reported cases of discontinuation-induced refractoriness,
      where following a good long-term response, patients discontinue lithium, suffer a
      major recurrence, and then do not again respond as well or at all to lithium once
      it is reinstituted at previously effective doses. The development of tolerance
      has similarly been multiply documented where lithium doses are consistently
      maintained, but after an extended period of excellent responsiveness, affective
      episodes of increasing severity, frequency, or duration begin to break through.
      These two forms of acquired treatment resistance appear to have different
      underlying neurobiological mechanisms and require differential treatment
      strategies. LIMITATIONS: Recognition of acquired forms of lithium resistance
      depends on careful case descriptions and longitudinal monitoring of patients who
      are usually treated naturalistically and not in controlled clinical trials.
      CONCLUSION: To the extent that these forms of acquired lithium resistance can be
      better recognized and their development slowed, prevented, or ameliorated, it
      could yield substantial clinical and public health benefits in avoiding the
      morbidity and mortality that can accompany lithium non-responsive bipolar
      disorder.

PMID- 22154710
TI  - Interaction of pregnancy and autoimmune rheumatic disease.
AB  - During pregnancy, the fetus represents a natural allograft that is not normally
      rejected. While the maternal immune system retains the ability to respond to
      foreign antigens, tolerance mechanisms are up-regulated to protect the fetus from
      immunologic attacks by the mother. The profound immunologic adaptations during
      and after pregnancy do influence maternal autoimmune rheumatic diseases in
      several ways. One is triggering the onset of a rheumatic disease in the post
      partum period, the other influencing disease activity of established rheumatic
      disease. The review will discuss the mechanisms of increased susceptibility of
      rheumatoid arthritis (RA) in the first year post partum with a specific emphasis
      on the role of fetal cells or antigens persisting in the maternal circulation (so
      called microchimerism). Furthermore, the different influences of pregnancy on
      established rheumatic diseases will be highlighted. A marked beneficial effect of
      pregnancy is observed on RA whereas several other rheumatic diseases as
      ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) show either no
      particular effect or an aggravation of symptoms during pregnancy. Differences
      emerging in regard to modulation of disease symptoms during pregnancy seem
      related to response to hormones, the type of cytokine profile and immune response
      prevailing as well as further downstream interactions of molecular pathways that
      are important in disease pathogenesis.

PMID- 22154709
TI  - Low prevalence of depressive disorder in ambulatory advanced cancer patients
      using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN 2.1).
AB  - Depressive disorder is assumed to be highly prevalent in advanced cancer
      patients, but the diagnosis of depressive disorder in patients with advanced
      cancer is difficult. The more robust the assessment instrument to diagnose
      depressive disorder is, the lower the reported prevalence of depressive disorder
      in advanced cancer patients. This study confirms a low prevalence of depressive
      disorder (3%) in 64 advanced cancer outpatients using a robust structured
      clinical assessment (SCAN 2.1). Furthermore, in this article we discuss possible
      implications of using predefined psychiatric labeling in the assessment of mood
      symptoms in advanced cancer patients.

PMID- 22154711
TI  - Ovarian failure and polycystic ovary syndrome.
AB  - The human ovary is commonly the target of an autoimmune attack leading to the
      ovarian dysfunction which can be manifested as premature ovarian failure (POF),
      polycystic ovary syndrome (PCOS), unexplained infertility as well as
      endometriosis. In case of POF, the evidence for an autoimmune etiology is based
      on the presence of lymphocytic oophoritis, autoantibodies to ovarian antigens and
      association with other autoimmune disorders, which was clearly documented in many
      studies. The search for antiovarian antibodies has been undertaken in numerous
      studies, especially in patients with POF, however their results are still
      conflicting particularly due to difference in laboratory methods as well as many
      ovarian components being potential antigens. On the other side the autoimmune
      etiology of PCOS is still debated and was documented in some cases. Association
      of PCOS with non-organ specific autoimmune disorders is controversial; however
      association with autoimmune thyroid disease was well demonstrated in some
      studies.

PMID- 22154713
TI  - A method for accurately designing flaps for use in reconstructive surgery of the
      oral and oropharyngeal region using surgical wire.

PMID- 22154712
TI  - Endpoint measures in the mdx mouse relevant for muscular dystrophy pre-clinical
      studies.
AB  - Loss of mobility influences the quality of life for patients with neuromuscular
      diseases. Common measures of mobility and chronic muscle damage are the six
      minute walk test and serum creatine kinase. Despite extensive pre-clinical
      studies of therapeutic approaches, characterization of these measures is
      incomplete. To address this, a six-minute ambulation assay, serum creatine
      kinase, and myoglobinuria were investigated for the mdx mouse, a dystrophinopathy
      mouse model commonly used in pre-clinical studies. mdx mice ambulated shorter
      distances than normal controls, a disparity accentuated after mild exercise. An
      asymmetric pathophysiology in mdx mice was unmasked with exercise, and peak
      measurements of serum creatine kinase and myoglobinuria were identified. Our data
      highlights the necessity to consider asymmetric pathology and timing of
      biomarkers when testing potential therapies for muscular dystrophy.

PMID- 22154714
TI  - The congenital cleft nipple and its surgical treatment.
AB  - Congenital variations of the shape and structure of the nipple lacks coverage in
      the medical literature. We present four cases of a specific and unique congenital
      nipple anomaly, the cleft nipple. Each woman had a normal contralateral breast
      and nipple-areola complex. Three of the four cases were corrected surgically with
      no complications experienced. Included in the discussion is a description of the
      techniques used in the corrective surgery and a review of the current literature
      on associated variations of normality.

PMID- 22154715
TI  - A simplified landmark for the facial nerve trunk in parotidectomy: the
      sternocleidomastoid origin.

PMID- 22154716
TI  - Facial paediatric desmoid fibromatosis: a case series, literature review and
      management algorithm.
AB  - Desmoid fibromatosis (also known as infantile or aggressive fibromatosis) is a
      rare soft tissue tumour that is occasionally seen in children. Although
      histologically benign, its growth pattern is highly aggressive often showing
      invasion of surrounding musculature and bone. Frequently found in cosmetically
      sensitive areas, complete excision can present a challenging problem. However,
      incomplete surgical excision is associated with high recurrence rates and
      although the disease responds to chemo and radiotherapy, both carry significant
      risks in young children. The management of four paediatric desmoid fibromatoses
      occurring in the midface is discussed. The recent and pertinent literature is
      comprehensively reviewed and an algorithm for the management of paediatric
      desmoid fibromatoses is proposed.

PMID- 22154717
TI  - Missing value imputation in DNA microarrays based on conjugate gradient method.
AB  - Analysis of gene expression profiles needs a complete matrix of gene array
      values; consequently, imputation methods have been suggested. In this paper, an
      algorithm that is based on conjugate gradient (CG) method is proposed to estimate
      missing values. k-nearest neighbors of the missed entry are first selected based
      on absolute values of their Pearson correlation coefficient. Then a subset of
      genes among the k-nearest neighbors is labeled as the best similar ones. CG
      algorithm with this subset as its input is then used to estimate the missing
      values. Our proposed CG based algorithm (CGimpute) is evaluated on different data
      sets. The results are compared with sequential local least squares (SLLSimpute),
      Bayesian principle component analysis (BPCAimpute), local least squares
      imputation (LLSimpute), iterated local least squares imputation (ILLSimpute) and
      adaptive k-nearest neighbors imputation (KNNKimpute) methods. The average of
      normalized root mean squares error (NRMSE) and relative NRMSE in different data
      sets with various missing rates shows CGimpute outperforms other methods.

PMID- 22154718
TI  - Acute myocardial infarction in women: is there a sex disparity between door-to
      balloon time and clinical outcomes?

PMID- 22154719
TI  - The fixation strength of scaphoid bone screws: an in vitro investigation using
      polyurethane foam.
AB  - PURPOSE: To compare the compression strength and pull-apart resistance of 5
      single-piece scaphoid bone compression screws (Acutrak, Asnis, Herbert, Herbert
      Whipple, and Little Grafter), with those of 2 dual-component screws (Kompressor
      and TwinFix). METHODS: Two blocks of polyurethane foam were compressed with a
      screw while held in a tension test machine, with the force measured at full
      insertion of the screw. The 2 blocks were then pulled apart, and the maximum
      resistive force was measured. RESULTS: The dual-component screws (Kompressor and
      TwinFix) gave greater compression force than the single-component screws, with
      the Kompressor screw giving statistically significantly greater compression than
      the TwinFix. The pull-apart resistance forces did not show such clear
      differences. CONCLUSIONS: The Kompressor screw achieves the greatest compressive
      forces and has one of the highest pull-apart forces. CLINICAL RELEVANCE: When
      compression and pull-apart resistance are considered, the Kompressor screw has
      advantages over other methods of scaphoid fixation.

PMID- 22154720
TI  - Chemotherapy extravasation injuries.

PMID- 22154721
TI  - Single versus double end-to-side nerve grafts in rats.
AB  - PURPOSE: Although the end-to-side nerve repair technique has been used
      clinically, it has not yet produced consistent motor and sensory recovery in
      patients. The aim of this study was to investigate whether end-to-side double
      nerve grafts display more axonal regeneration compared with a single nerve graft
      in a rat lower limb preparation. METHODS: The lower limbs of 96 Wister rats were
      used in experiments comparing single and double end-to-side nerve grafts. Left
      peroneal nerves were harvested and grafted between the right peroneal and tibial
      nerves. A single graft was attached end-to-side to the peroneal and tibial nerves
      through an epineural window (single graft group, n = 24). Two grafts were
      performed in the same manner in the double graft group (n = 24). The peroneal
      nerve was exposed in positive controls (n = 24) and no graft was performed in
      negative controls (n = 24). We recorded action potentials and moist weights of
      the left tibialis anterior muscle at each time point. Fluoro-Gold-labeled
      (Fluorochrome, Denver, CO) dorsal root ganglion neurons from L1 to L6 were
      counted using fluorescence microscopy and compared among the 4 groups. RESULTS:
      In both single and double groups, the amplitude and the tibialis anterior muscle
      weight increased significantly compared with negative controls but remained lower
      than those measured in positive controls. There was no significant difference
      between single and double groups. In Fluoro-Gold-labeled neurons, there was also
      no significant difference between single and double groups. CONCLUSIONS: The
      study showed that regeneration of motor and sensory nerve fibers was possible
      using 2 end-to-side nerve grafts. However, there was no significant difference
      between single and double grafts. This might suggest a therapeutic limitation of
      nerve transplants using 2 end-to-side nerve grafts. CLINICAL RELEVANCE: Double
      end-to-side repair attracts both motor and sensory axons, and this results in a
      medium degree of recovery of function; however, double end-to-side nerve grafting
      does not appear to offer any advantage over a single end-to-side graft.

PMID- 22154722
TI  - Pediatric forearm fractures: spotting and managing the bad actors.

PMID- 22154723
TI  - Reconstruction of an entire metacarpal and metacarpophalangeal joint using a
      fibular osteocutaneous free flap and silicone arthroplasty.
AB  - Radical resection of the entire ring finger metacarpal for a giant cell tumor
      resulted in a bony defect extending from the distal surface of the hamate to the
      proximal surface of the proximal phalanx. We reconstructed the metacarpal with a
      custom-contoured free fibular osteocutaneous flap and maintained motion at the
      new fibulophalangeal joint using a silicone arthroplasty. At 4.5 years
      postoperatively, the patient has shown no signs of recurrence of the giant cell
      tumor. The silicone arthroplasty has maintained 15 degrees  to 85 degrees  of
      motion at the new joint. Because of its similar shape to a metacarpal and because
      it allows faster bony healing compared with a nonvascularized fibular bone graft,
      a free vascularized fibular bone graft is an ideal candidate for reconstruction
      of extensive defects of the metacarpals, and placement of a silicone spacer in
      its distal medullary cavity can preserve motion at the new metacarpophalangeal
      joint.

PMID- 22154724
TI  - Favorable effects of alemtuzumab on allospecific regulatory T-cell generation.
AB  - We studied the effects of alemtuzumab on T-regulatory cells (Tregs) during
      alloactivation, first by differences in depletion of various naive versus
      alloactivated cell subsets in peripheral blood of healthy volunteers, then by
      adding serial concentrations to human leukocyte antigen (HLA)-DR-matched and 
      mismatched responding and stimulating cells in mixed lymphocyte reaction (MLR).
      Lymphoproliferation inhibition and the development of proliferating
      carboxyfluorescein succinimidyl ester (CFSE)-diluted CD4(+)CD25(high)CD127(
      )FOXP3(+) (phenotypic) Tregs by flow cytometry were measured. Also, the ability
      of alemtuzumab-treated versus nontreated MLR generated CD4(+)CD127(-) cells to
      allospecifically inhibit MLRs and recruit additional responding Tregs was tested.
      We found a more pronounced refractoriness of alloactivated versus naive
      CD4(+)CD25(high) cells to alemtuzumab induced lymphodepletion. Alemtuzumab dose
      dependently inhibited lymphoproliferation while amplifying percentages of MLR
      generated Tregs. This was somewhat augmented by human complement addition. CD127(
      )CD4(+) cells immunoselected after 7 days from alemtuzumab-treated MLRs
      allospecifically inhibited lymphoproliferation and recruited additional Tregs in
      fresh MLR-responding cells, similar to modulators derived from MLRs without drug
      addition (media). Addition of tacrolimus and sirolimus to alemtuzumab further
      inhibited MLR proliferation. However, Treg percentages were markedly higher with
      sirolimus. These results support the notion that alemtuzumab induces
      immunoregulation in naive T cells undergoing alloactivation absent
      presensitization, especially used in conjunction with maintenance SRL.

PMID- 22154725
TI  - HLA-A, -B, and -DRB1 allelic and haplotypic diversity in a sample of bone marrow
      volunteer donors from Rio Grande do Sul State, Brazil.
AB  - The HLA A, B, and DRB1 allele, phenotype, and haplotype frequencies were studied
      in a sample of 5,000 volunteer bone marrow donors registered at the Brazilian
      Volunteer Bone Marrow Donor Registry. The participants live in the state of Rio
      Grande do Sul and were classified according to ethnic group (4,428 Caucasians,
      324 mestizos [mixed race], and 248 blacks). Typing was performed using the
      polymerase chain reaction sequence-specific oligonucleotide method combined with
      Luminex technology. Twenty-one HLA-A, 33 HLA-B, and 13 HLA-DRB1 allele groups
      were identified. The most frequent allele groups for each locus were A*02, B*35,
      and DRB1*13. The most frequent haplotypes were A*01 B*08 DRB1*03 in Caucasians
      and mestizos and A*02 B*15 and DRB1*04 in blacks. The allele frequencies were
      compared with samples from different Brazilian regions. In most comparisons no
      significant differences were found. The most significant differences were
      observed in the comparison of the groups of our sample, indicating that human
      leukocyte antigen (HLA) is a good marker to distinguish among people from
      different ethnic groups. The data provide insight on the knowledge of HLA
      diversity in the population of Rio Grande do Sul and in the search for a better
      match for transplant.

PMID- 22154726
TI  - Use of baseline prostate-specific antigen measurements to personalize prostate
      cancer screening.

PMID- 22154727
TI  - A plea for long-term surveillance in bacillus Calmette-Guerin-treated non-muscle
      invasive bladder cancer.

PMID- 22154728
TI  - Comparison of open and minimally invasive partial nephrectomy for renal tumors 4
      7 centimeters.
AB  - BACKGROUND: Indications for partial nephrectomy (PN) in the treatment of renal
      cell carcinoma are evolving, particularly for larger, more complex tumors.
      OBJECTIVE: Compare single-institution outcomes for minimally invasive partial
      nephrectomy (MIPN) and open partial nephrectomy (OPN) for tumors>4-7 cm. DESIGN,
      SETTING, AND PARTICIPANTS: A total of 2290 patients underwent PN from 2002 to
      2010 at Memorial Sloan-Kettering Cancer Center; 280 had >4-7 cm renal cortical
      tumors. Of these 280 patients, 230 had pT1b, 48 had pT3a, and 2 had
      angiomyolipomas; 226 underwent OPN and 54 underwent MIPN (16 robot-assisted and
      37 laparoscopic procedures). Perioperative management was uniform on the clinical
      pathway. Perioperative data, clinicopathologic variables, complications within 30
      d, and oncologic outcomes were reviewed. MEASUREMENTS: Estimated glomerular
      filtration rate (eGFR) was calculated using the Chronic Kidney Disease
      Epidemiology Collaboration equation. Complications were reported from
      prospectively collected data based on a modified Clavien system. The Fisher exact
      and Mann-Whitney U tests were used for descriptive statistical analysis. Kaplan
      Meier methods were used to estimate survival. RESULTS AND LIMITATIONS: Median
      follow-up for OPN and MIPN was 29 and 13 mo, respectively. There were no
      statistically significant differences in age, gender, preoperative American
      Society of Anesthesiologists score, laterality, histologic subtype, tumor size,
      tumor stage, or margin status between procedures. Univariate analysis revealed
      significantly greater values in the OPN group for preoperative eGFR, renal artery
      clamp time, estimated blood loss, use of renal hypothermia, and length of stay.
      Differences in overall survival and recurrence-free survival were not
      statistically significant; however, short median follow-up times limit
      comparison. There was no significant difference in the number of complications
      grade>=3 (p=0.1) or urine leaks requiring intervention (p=0.7). Limitations
      include the retrospective nature of the study and the possibility of selection
      bias. CONCLUSIONS: OPN and MIPN procedures performed in patients with tumors>4-7
      cm offer acceptable and comparable results in terms of operative, functional, and
      convalescence measures, regardless of approach.

PMID- 22154730
TI  - Open radical retropubic prostatectomy using high anterior release of the levator
      fascia and constant haptic feedback in bilateral neurovascular bundle
      preservation plus early postoperative phosphodiesterase type 5 inhibition: a
      contemporary series.
AB  - BACKGROUND: Patients with newly diagnosed localized prostate cancer who choose
      surgery want cure and decent quality of life, namely, pad-free urinary control
      and, often, erectile function satisfactory for sexual intercourse. OBJECTIVE:
      Determine in a prospective study the positive surgical margin rate and functional
      outcomes for a consecutive series of patients undergoing open radical retropubic
      prostatectomy (ORRP) with bilateral neurovascular bundle preservation (BNVBP)
      performed by one experienced surgeon. DESIGN, SETTING, AND PARTICIPANTS: Of 197
      consecutive patients undergoing BNVBP during 2008, 123 were evaluable, allowing
      both immediate postoperative phosphodiesterase type 5 inhibition (PDE5i) and a
      third-party questionnaire with validated urinary and erectile function domains
      provided preoperatively and at 3, 6, and 12 mo postoperatively. INTERVENTION: Two
      interventions were used: (1) ORRP with *4.3 optical loupes and constant digital
      tactile monitoring during BNVBP preceded by high anterior release (HAR) of
      levator fascia and neurovascular bundles and (2) early postoperative PDE5i.
      MEASUREMENTS: Age; biopsy Gleason score; clinical stage; preoperative prostate
      specific antigen level; pathologic grade; stage; margin status; University of
      California, Los Angeles Prostate Cancer Index domain for urinary pad use and
      bother; and International Index of Erectile Function-5 (IIEF-5) were used.
      RESULTS AND LIMITATIONS: Surgical margins were positive in 1 of the 123 evaluable
      patients (1%). At 1 yr, 95% of patients were pad-free. Satisfactory erectile
      function was achieved by 109 patients (89%): 82 (67%) scored an IIEF-5 of 22-25,
      and 27 (22%) scored <22-25 with >=4 on either satisfaction or confidence
      questions or achieved "full" erection within the first year. Mean hospital stay
      was 1.3 d. Limitations were (1) observational, noncomparative, single-surgeon
      series and (2) in third-party methodology, failure to capture patient answers for
      all questionnaire intervals with resultant inability to address durability of
      functional results for all patients. CONCLUSIONS: ORRP using *4.3 optical loupe
      magnification, constant haptic feedback in BNVBP with HAR, and immediate
      postoperative PDE5i yielded satisfactory outcomes.

PMID- 22154731
TI  - Development and validation of a new adenosine-independent index of stenosis
      severity from coronary wave-intensity analysis: results of the ADVISE (ADenosine
      Vasodilator Independent Stenosis Evaluation) study.
AB  - OBJECTIVES: The purpose of this study was to develop an adenosine-independent,
      pressure-derived index of coronary stenosis severity. BACKGROUND: Assessment of
      stenosis severity with fractional flow reserve (FFR) requires that coronary
      resistance is stable and minimized. This is usually achieved by administration of
      pharmacological agents such as adenosine. In this 2-part study, we determine
      whether there is a time when resistance is naturally minimized at rest and assess
      the diagnostic efficiency, compared with FFR, of a new pressure-derived adenosine
      free index of stenosis severity over that time. METHODS: A total of 157 stenoses
      were assessed. In part 1 (39 stenoses), intracoronary pressure and flow velocity
      were measured distal to the stenosis; in part 2 (118 stenoses), intracoronary
      pressure alone was measured. Measurements were made at baseline and under
      pharmacologic vasodilation with adenosine. RESULTS: Wave-intensity analysis
      identified a wave-free period in which intracoronary resistance at rest is
      similar in variability and magnitude (coefficient of variation: 0.08 +/- 0.06 and
      284 +/- 147 mm Hg s/m) to those during FFR (coefficient of variation: 0.08 +/-
      0.06 and 302 +/- 315 mm Hg s/m; p = NS for both). The resting distal-to-proximal
      pressure ratio during this period, the instantaneous wave-free ratio (iFR),
      correlated closely with FFR (r = 0.9, p < 0.001) with excellent diagnostic
      efficiency (receiver-operating characteristic area under the curve of 93%, at FFR
      <0.8), specificity, sensitivity, negative and positive predictive values of 91%,
      85%, 85%, and 91%, respectively. CONCLUSIONS: Intracoronary resistance is
      naturally constant and minimized during the wave-free period. The instantaneous
      wave-free ratio calculated over this period produces a drug-free index of
      stenosis severity comparable to FFR. (Vasodilator Free Measure of Fractional Flow
      Reserve [ADVISE]; NCT01118481).

PMID- 22154732
TI  - A novel approach for enhancing metal ion separation using acoustic nebulisation.
AB  - A novel technique for anionic surfactant assisted separation and preconcentration
      of metal cations was developed using ultrasound induced nebulization at MHz
      frequency. The ions of copper, zinc, cadmium, and calcium were used as model
      analytes. Analysis of the aerosol using flame atomic absorption spectrometry
      showed enrichment factors for the metal ions studied between 5 and 8, when dilute
      solutions containing sodium dodecylsulfate and the metal ions were nebulized. The
      mechanism of metal ion enrichment was explained based on surfactant adsorption
      and the droplet model for aerosol droplets. It was demonstrated that further
      increase in the enrichment factor could be achieved by increasing the ultrasound
      frequency, thus producing smaller droplets.

PMID- 22154733
TI  - Oculoauriculovertebral spectrum with a full range of severe clinical
      manifestations--case report.
AB  - Oculoauriculovertebral spectrum (OAVS) is a rare congenital malformation
      consisting of epibulbar dermoids, lid colobomas, auricular deformities,
      hypoplasia of the soft and bony tissues of the face, associated oral deformities
      and vertebral anomalies. This report presents a child with a choroid of the right
      eye, coloboma of the upper eyelid, epibulbar dermoid of the left eye, mandibular
      hypoplasia, facial asymmetry, bilateral complete cleft lip and palate, hypoplasia
      of the left alar cartilage, appendage of the left nose, butterfly vertebral
      defects of Th-1, Th-2 and abnormality of rib XI. Widened sulci of frontal and
      parietal lobes, bilateral white matter density decrease and calcifications of
      falx cerebelli were noted. Axial hypotony and delayed psycho-motor development
      were apparent. This rare case presents a range of severe clinical manifestations
      of oculoauriculovertebral spectrum. Despite a normal cervical vertebral column,
      tracheostenosis was present. It caused difficulties in tracheal intubation,
      creating the need for a tracheostomy, and death after a failed attempt at
      decannulation. This case indicates that in patients with clinical manifestations
      including cerebral anomalies, a risk of respiratory insufficiency should be
      always taken under consideration, when planning surgery. 

PMID- 22154734
TI  - [Seasonal influenza vaccination in children and adolescents. Recommendations of
      the CAV-AEP for the campaign].
AB  - The Advisory Committee on Vaccines of the Spanish Association of Paediatrics
      establishes annual recommendations on influenza vaccination in childhood before
      the onset of influenza season. Routine influenza vaccination is particularly
      beneficial when the strategy is aimed at children older than 6 months of age with
      high-risk conditions and their home contacts. The recommendation of influenza
      vaccination in health workers with children is also emphasized.

PMID- 22154735
TI  - Adenovirus-based oral vaccine for rabbit hemorrhagic disease.
AB  - Vaccine antigens for rabbit hemorrhagic disease virus (RHDV) are currently
      derived from inactivated RHDV obtained from the livers of experimentally infected
      rabbits or from several recombinant immunogens. However, the application of these
      vaccine antigens has been restricted because of biosecurity and immunity
      characteristics. In the current study, a recombinant adenovirus expressing the
      RHDV capsid protein (VP60) was constructed and the expression of the recombinant
      protein was identified through western blot analysis using RHDV-positive rabbit
      sera. Eighteen rabbits were immunized by injection, direct oral instillation, or
      using bait. They were challenged with RHDV isolate three weeks after boost
      immunization. In all cases, the rabbits immunized with the recombinant adenovirus
      developed RHDV-specific antibodies and cell immune response. The rabbits injected
      with the recombinant adenovirus were completely protected against RHDV challenge.
      The adenovirus expression system may provide a strategy for the immunization of
      rabbits, particularly for the control of RHDV in wild rabbits.

PMID- 22154736
TI  - Veridical and false memory for scenic material in posttraumatic stress disorder.
AB  - The question whether memory aberrations in posttraumatic stress disorder (PTSD)
      also manifest as an increased production of false memories is important for both
      theoretical and practical reasons, but is yet unsolved. Therefore, for the
      present study we investigated veridical and false recognition in PTSD with a new
      scenic variant of the Deese-Roediger-McDermott (DRM) paradigm, which was
      administered to traumatized individuals with PTSD (n=32), traumatized individuals
      without PTSD (n=30), and non-traumatized controls (n=30). The PTSD group neither
      produced higher rates of false memories nor expressed more confidence in errors,
      but did show inferior memory sensitivity. Whereas depressive symptoms did not
      correlate with veridical nor false recognition, state dissociation was positively
      associated with false memories.

PMID- 22154738
TI  - The Yellow Brick Road: a values based curriculum model.
AB  - Within the United Kingdom, the Nursing and Midwifery Council (NMC) requires that
      nurses and midwives are of 'good character' at the point of registration. This
      paper sets out how good character has been conceptualised within one U.K. higher
      education institution and presents a model of "values based enquiry" which aims
      to develop the 'character' of students. The paper presents three qualities ("the
      heart", "the nerve" and "the brain") which represent 'good character' and which
      are believed to underpin values based Nursing or Midwifery practice. The
      development of these qualities is argued to be reliant upon helping students to
      develop intrinsic professional values of care and compassion. The role of these
      character qualities in nursing practice and education is outlined, as are the
      ways in which they have led to the development of a model for values based
      enquiry. This model represents a vision of the nature of professional education
      which may be shared by staff and students, whilst offering a model for learning
      and teaching based upon recognised educational principles. An argument is
      advanced that the adoption of a values based enquiry model may develop and
      nurture the habits of mind which are necessary for the development of 'good
      character'.

PMID- 22154739
TI  - Aminoguanidine normalizes ET-1-induced aortic contraction in type 2 diabetic
      Otsuka Long-Evans Tokushima Fatty (OLETF) rats by suppressing Jab1-mediated
      increase in ET(A)-receptor expression.
AB  - Circulating levels of endothelin (ET)-1 are increased in the diabetic state, as
      is endogenous ET(A)-receptor-mediated vasoconstriction. However, the responsible
      mechanisms remain unknown. We hypothesized that ET-1-induced vasoconstriction is
      augmented in type 2 diabetes with hyperglycemia through an increment in advanced
      glycation end-products (AGEs). So, we investigated whether treatment with
      aminoguanidine (AG), an inhibitor of AGEs, would normalize the ET-1-induced
      contraction induced by ET-1 in strips of thoracic aortas isolated from OLETF rats
      at the chronic stage of diabetes. In such aortas (vs. those from age-matched
      genetic control LETO rats): (1) the ET-1-induced contraction was enhanced, (2)
      the levels of HIF1alpha/ECE1/plasma ET-1 and plasma CML-AGEs were increased, (3)
      the ET-1-stimulated ERK phosphorylation mediated by ET(A)-R was increased, (4)
      the expression level of Jab1-modified ET(A)-R protein was reduced, and (5) the
      expression level of O-GlcNAcylated ET(A)-R protein was increased. Aortas isolated
      from such OLETF rats that had been treated with AG (50mg/kg/day for 10 weeks)
      exhibited reduced ET-1-induced contraction, suppressed ET-1-stimulated ERK
      phosphorylation accompanied by down-regulation of ET(A)-R, and increased
      modification of ET(A)-R by Jab1. Such AG-treated rats exhibited normalized plasma
      ET-1 and CML-AGE levels, and their aortas exhibited decreased HIF1alpha/ECE1
      expression. However, such AG treatment did not alter the elevated levels of
      plasma glucose or insulin, or systolic blood pressure seen in OLETF rats. These
      data from the OLETF model suggest that within the timescale studied here, AG
      normalizes ET-1-induced aortic contraction by suppressing ET(A)-R/ERK activities
      and/or by normalizing the imbalance between Jab1 and O-GlcNAc in type 2 diabetes.

PMID- 22154740
TI  - Thermodynamically based solvent design for enzymatic saccharide acylation with
      hydroxycinnamic acids in non-conventional media.
AB  - Enzyme-catalyzed synthesis has been widely studied with lipases (EC 3.1.1.3), but
      feruloyl esterases (FAEs; EC 3.1.1.73) may provide advantages such as higher
      substrate affinity and regioselectivity in the synthesis of hydroxycinnamate
      saccharide esters. These compounds are interesting because of their
      amphiphilicity and antioxidative potential. Synthetic reactions using mono- or
      disaccharides as one of the substrates may moreover direct new routes for biomass
      upgrading in the biorefinery. The paper reviews the available data for enzymatic
      hydroxycinnamate saccharide ester synthesis in organic solvent systems as well as
      other enzymatic hydroxycinnamate acylations in ionic liquid systems. The choice
      of solvent system is highly decisive for enzyme stability, selectivity, and
      reaction yields in these synthesis reactions. To increase the understanding of
      the reaction environment and to facilitate solvent screening as a crucial part of
      the reaction design, the review explores the use of activity coefficient models
      for describing these systems and - more importantly - the use of group
      contribution model UNIFAC and quantum chemistry based COSMO-RS for thermodynamic
      predictions and preliminary solvent screening. Surfactant-free microemulsions of
      a hydrocarbon, a polar alcohol, and water are interesting solvent systems because
      they accommodate different substrate and product solubilities and maintain enzyme
      stability. Ionic liquids may provide advantages as solvents in terms of increased
      substrate and product solubility, higher reactivity and selectivity, as well as
      tunable physicochemical properties, but their design should be carefully
      considered in relation to enzyme stability. The treatise shows that thermodynamic
      modeling tools for solvent design provide a new toolbox to design enzyme
      catalyzed synthetic reactions from biomass sources.

PMID- 22154741
TI  - Rapid near infrared spectroscopy for prediction of enzymatic hydrolysis of corn
      bran after various pretreatments.
AB  - Efficient generation of a fermentable hydrolysate is a primary requirement in the
      utilization of fibrous plant biomass as feedstocks in bioethanol processes. The
      first biomass conversion step usually involves a hydrothermal pretreatment before
      enzymatic hydrolysis. The purpose of the pretreatment step is to increase the
      responsivity of the substrate to enzymatic attack and the type of pretreatment
      affects the enzymatic conversion efficiency. Destarched corn bran is a fibrous,
      heteroxylan-rich side-stream from the starch industry which may be used as a
      feedstock for bioethanol production or as a source of xylose for other purposes.
      In the present study we demonstrate the use of diffuse reflectance near infrared
      spectroscopy (NIR) as a rapid and non-destructive analytical tool for evaluation
      of pretreatment effects on destarched corn bran. NIR was used to achieve
      classification between 43 differently pretreated corn bran samples using
      principal component analysis (PCA) and hierarchal clustering algorithms.
      Quantification of the enzymatically released monosaccharides by HPLC was used to
      design multivariate calibration models (biPLS) on the NIR spectra. The models
      could predict the enzymatic release of different levels of arabinose, xylose and
      glucose from all the differently pretreated destarched corn bran samples. The
      present study also demonstrates a generic, non-destructive solution to determine
      the enzymatic monosaccharide release from polymers in biomass side-streams,
      thereby potentially replacing the cumbersome HPLC analysis.

PMID- 22154742
TI  - Study of local structure and Li dynamics in Li(4+x)Ti(5)O(12) (0 <= x <= 5) using
      (6)Li and (7)Li NMR spectroscopy.
AB  - We studied the local structure and the Li ion dynamics in electrochemically and
      chemically prepared Li(4+x)Ti(5)O(12) with x = 0...5. We used magic-angle
      spinning (7)Li NMR on samples with different Li contents to investigate the sites
      that are occupied/emptied during Li insertion/removal. While the electrochemical
      measurements show a lithium insertion in two steps, 1D MAS NMR as a function of
      the lithium content shows that the overall spectral evolution observed during
      lithium insertion is inverted during lithium removal. Thereby the second
      insertion step is associated with an increased structural disorder. For samples
      with x = 0, 2, 3, and about 5, we performed temperature-dependent measurements of
      the (7)Li NMR relaxation rates T(1)(-1), T(2)(-1), and T(1rho)(-1) to study the
      dynamics of the Li ions. For the samples with x = 0, 2, and 3, activation
      energies of (0.45 +/- 0.1)eV were obtained. The highest mobility of the Li ions
      is observed for the samples with x = 2 and 3. Results from (6)Li and (7)Li 2D
      exchange MAS NMR spectroscopy on samples with x = 2 and 4 show that magnetization
      transfer for (7)Li below 323K is dominated by spin diffusion.

PMID- 22154743
TI  - A dimerized single-chain variable fragment system for the assessment of
      neutralizing activity of phage display-selected antibody fragments specific for
      cytomegalovirus.
AB  - Cytomegalovirus (CMV) causes severe sequelae in congenitally infected newborns
      and may cause life-threatening disease in immuno-deficient patients. Recent
      findings demonstrate the possibility to alleviate the disease by infusing
      intravenous immunoglobulin G (IgG) preparations, indicating that antibodies are
      an effective therapeutic option. Modern molecular methodologies, like phage
      display, allow for the development of specific antibodies targeting virtually any
      antigen, including those of CMV. However, such methodologies do not in general
      result in products that by themselves mediate biological activity. To facilitate
      a semi-high-throughput approach for functional screening in future efforts to
      develop efficacious antibodies against CMV, we have integrated two different
      approaches to circumvent potential bottlenecks in such efforts. Firstly, we
      explored an approach that permits easy transfer of antibody fragment encoding
      genes from commonly used phage display vectors into vectors for the production of
      divalent immunoglobulins. Secondly, we demonstrate that such proteins can be
      applied in a novel reporter-based neutralization assay to establish a proof-of
      concept workflow for the generation of neutralizing antibodies against CMV. We
      validated our approach by showing that divalent antibodies raised against the
      antigenic domain (AD)-2 region of gB effectively neutralized three different CMV
      strains (AD169, Towne and TB40/E), whereas two antibodies against the AD-1 region
      of gB displayed minor neutralizing capabilities. In conclusion, the methods
      investigated in this proof-of-concept study enables for a semi-high-throughput
      workflow in the screening and investigation of biological active antibodies.

PMID- 22154744
TI  - An integrated approach to remove Cr(VI) using immobilized Chlorella minutissima
      grown in nutrient rich sewage wastewater.
AB  - The potential of an integrated system for sewage wastewater treatment and
      biosorption of chromium(VI) was evaluated using immobilized Chlorella minutissima
      cells. Immobilized algal cells were grown in sewage wastewater in designed
      photobioreactor for 48 h and then subjected to removal of Cr(VI) from synthetic
      wastewater. The effect of pH, Cr(VI) concentration, biosorbent dose on Cr(VI)
      removal was investigated. C. minutissima showed a higher NH(4)(+)-N and PO(4)(3-)
      P removal efficiency (above 99% removal) than the NO(3)(2-)-N (58% removal) in 48
      h. Biosorption of Cr(VI) was found to be highly dependent on solution pH,
      biosorbent dose and initial Cr(VI) concentration. Maximum Cr(VI) uptake 57.33 mg
      Cr(VI)/g dry biosorbent/L of solution was observed at pH2 with 20% (w/v)
      biosorbent. Further more than 90% of total Cr adsorbed could be recovered using
      0.5 M NaOH as desorption medium.

PMID- 22154745
TI  - Bacterial cellulose production from cotton-based waste textiles: enzymatic
      saccharification enhanced by ionic liquid pretreatment.
AB  - Cotton-based waste textiles were explored as alternative feedstock for production
      of bacterial cellulose (BC) by Gluconacetobacter xylinus. The cellulosic fabrics
      were treated with the ionic liquid (IL) 1-allyl-3-methylimidazolium chloride
      ([AMIM]Cl). [AMIM]Cl caused 25% inactivation of cellulase activity at a
      concentration as low as of 0.02 g/mL and decreased BC production during
      fermentation when present in concentrations higher than 0.0005 g/mL. Therefore,
      removal of residual IL by washing with hot water was highly beneficial to
      enzymatic saccharification as well as BC production. IL-treated fabrics exhibited
      a 5-7-fold higher enzymatic hydrolysis rate and gave a seven times larger yield
      of fermentable sugars than untreated fabrics. BC from cotton cloth hydrolysate
      was obtained at an yield of 10.8 g/L which was 83% higher than that from the
      culture grown on glucose-based medium. The BC from G. xylinus grown on IL-treated
      fabric hydrolysate had a 79% higher tensile strength than BC from glucose-based
      culture medium which suggests that waste cotton pretreated with [AMIM]Cl has
      potential to serve as a high-quality carbon source for BC production.

PMID- 22154746
TI  - Experimental study on ash fusion characteristics of biomass.
AB  - In this study, ash fusion characteristics (AFC) of biomass red pine, corn straw,
      Bermuda grass and bamboo are investigated. Results of this study show that ash
      melting temperatures are higher when samples are ashed at 815  degrees C than at
      600  degrees C, but the differences are small. The ash deformation temperatures
      of pine and straw are over 1100  degrees C, but the ash deformation temperatures
      of Bermuda grass and bamboo are lower than the former biomass. Also, Bermuda
      grass and bamboo are prone to sintering phenomenon when burning. In the
      thermogravimetric experiment on ash, the heating process can be divided into
      three stages, namely water evaporation, oxidation of organic compounds and
      evaporation, and reaction of inorganic components. The ash of Bermuda grass and
      bamboo contains more unburned organic matters because of sintering, and higher
      calcium content in pine ash results in a more mass loss in the third stage. The
      ash fusion characteristics for co-combustion of biomass with coal are
      investigated. It is found that the ash melting temperature firstly decreases and
      then increases with the content of the corn straw increase, changing as "V"
      shape.

PMID- 22154747
TI  - Immobilization of magnetic modified Flavobacterium ATCC 27551 using magnetic
      field and evaluation of the enzyme stability of immobilized bacteria.
AB  - The magnetic modified Flavobacterium sp. was prepared by covalently binding
      carboxylate-modified magnetic nanoparticles, and also, ionic adsorption of
      magnetic Fe(3)O(4) nanoparticles on the cell surface. The magnetic modified
      bacteria were immobilized by both internal and external magnetic fields. The pH
      stability and inherent resistance of the enzyme activity of the immobilized
      bacteria under acidic and alkaline conditions were increased. Immobilization of
      the magnetic modified bacteria using an external magnetic field improved the
      enzyme thermal stability. The results revealed that immobilization of the
      magnetic modified bacteria by an external magnetic field keeps 50% of the enzyme
      activity after 23.4, 16.6 and 6 h of incubation at 55  degrees C for the
      covalently binding of magnetic nanoparticles, the ionic adsorption of magnetic
      nanoparticles and the free cells, respectively. The results demonstrated the
      negative effect of various magnetic beads on the enzyme thermal stability of
      immobilized magnetic modified bacteria using an internal magnetic field.

PMID- 22154748
TI  - Effect of composting on the mobility of arsenic, chromium and nickel contained in
      kitchen and garden waste.
AB  - The study was focused on evaluation of possible changes in As, Cr, and Ni
      mobility and fractionation during composting of kitchen and garden waste. Fresh
      bio-waste taken up seasonally was thoroughly mixed with woodchips in the wet
      weight portion of 3:1 and the mixture was put into batch-wise aerated fermenters
      under 3 air flow rates. An increased drop in exchangeable Cr and Ni was found in
      kitchen and garden waste after 12 weeks of composting, respectively. The
      exchangeable content of As decreased only during kitchen waste composting. The
      order of fractions in the final compost was as follows:
      residual>oxidizable>exchangeable>reducible. The proportion of Cr and Ni in
      exchangeable fraction decreased after composting more than 3- and 4-fold,
      respectively. Results proved that an intensive composting process is a suitable
      method for immobilization of Cr and Ni, and for decreasing total As contained in
      household bio-waste.

PMID- 22154749
TI  - Microbially-enhanced composting of wet olive husks.
AB  - The production of a compost from olive wet husks is described. The process is
      enhanced through the use of starters prepared with virgin husks enriched with
      selected microbial cultures. This approach, with respect to composting without
      the use of starters, allows to achieve faster start of the process (10 vs. 45
      days), deeper humification (humification rate 19.2 vs. 12.2), shorter maturation
      time (2 vs. 4-5 months) and better detoxification of the starting material.
      Furthermore, the compost produced can effectively substitute for turf as a
      cultivation substrate in horticulture at greenhouse level, with beneficial
      effects on nutraceutical traits of tomato fruits.

PMID- 22154750
TI  - Qualitative characterization of the protein fraction of exopolymeric substances
      (EPS) extracted with EDTA from sludge.
AB  - Exopolymeric substances (EPS) were extracted by EDTA from activated and anaerobic
      granular sludge. Due to the presence of EDTA in EPS extract, interferences were
      pointed out for the characterization of EPS by means of the colorimetric methods
      and fluorescence spectroscopy. Other methods have been investigated to
      characterize the EPS protein fraction. Size exclusion chromatography (SEC),
      performed at a fluorescence excitation-emission matrix of 221/360 nm (tryptophan
      protein-like substances) for detection, was suitable and allowed obtaining a
      fingerprint of the protein-like substance fractions and determining apparent
      molecular weight (MW). Polyacrylamide gel electrophoresis (PAGE) was performed
      under either native or denaturing conditions. Various staining applications after
      EPS migration are effective in obtaining a protein (silver staining) or
      glycoprotein (PAS staining) fingerprint or MW distribution. SEC and PAGE are both
      appropriate techniques for the qualitative characterization of protein fractions
      from EPS extracted by EDTA and moreover differentiate EPS according to sludge
      origin and type.

PMID- 22154751
TI  - Prism adaptation enhances activity of intact fronto-parietal areas in both
      hemispheres in neglect patients.
AB  - Unilateral spatial neglect involves a failure to report or orient to stimuli in
      the contralesional (left) space due to right brain damage, with severe handicap
      in everyday activities and poor rehabilitation outcome. Because behavioral
      studies suggest that prism adaptation may reduce spatial neglect, we investigated
      the neural mechanisms underlying prism effects on visuo-spatial processing in
      neglect patients. We used functional magnetic resonance imaging (fMRI) to examine
      the effect of (right-deviating) prisms on seven patients with left neglect, by
      comparing brain activity while they performed three different spatial tasks on
      the same visual stimuli (bisection, search, and memory), before and after a
      single prism-adaptation session. Following prism adaptation, fMRI data showed
      increased activation in bilateral parietal, frontal, and occipital cortex during
      bisection and visual search, but not during the memory task. These increases were
      associated with significant behavioral improvement in the same two tasks. Changes
      in neural activity and behavior were seen only after prism adaptation, but not
      attributable to mere task repetition. These results show for the first time the
      neural substrates underlying the therapeutic benefits of prism adaptation, and
      demonstrate that visuo-motor adaptation induced by prism exposure can restore
      activation in bilateral brain networks controlling spatial attention and
      awareness. This bilateral recruitment of fronto-parietal networks may counteract
      the pathological biases produced by unilateral right hemisphere damage,
      consistent with recent proposals that neglect may reflect lateralized deficits
      induced by bilateral hemispheric dysfunction.

PMID- 22154752
TI  - Cyclic deformation-induced injury and differentiation of rat alveolar epithelial
      type II cells.
AB  - The injury and differentiation of alveolar epithelial type II cells induced by
      alveolar epithelial deformation play important roles in the pathophysiology of
      ventilator-induced lung injury and repair of the lung injury, respectively. We
      developed an in vitro rat model to investigate the effects of deformation
      amplitude, peak deformation, and minimum deformation on the viability and
      differentiation of type II cells. Rat primary alveolar epithelial type II cells
      were exposed to a variety of equibiaxial cyclic stretch protocols, and
      deformation-induced cell survival and differentiation were analyzed. Cell death
      increased when deformation consisted of change in cell surface area (DeltaSA) of
      0-37%, 0-50%, 12-50%, 37-50% (P=0.001, P<0.001, P<0.001, and P=0.003,
      respectively). When DeltaSA was at 12-37% and 12-50%, mRNA transcription (P=0.034
      and P=0.036) and protein expressions (P=0.008 and P=0.001) of caveolin-1 (a
      marker for the type I phenotype) increased, in contrast to the decrease of their
      mRNA transcription of surfactant protein C (a marker for the type II phenotype)
      (P=0.011, 0.002). These results suggest that amplitude or minimum deformation >=
      37% DeltaSA is an important cause of cell death, and amplitude >= 25% DeltaSA
      promotes cell differentiation. Appropriate amplitude (25% DeltaSA) can not only
      avoid cell death but also promote cell differentiation.

PMID- 22154753
TI  - A gentle mechanical skin stimulation technique for inhibition of micturition
      contractions of the urinary bladder.
AB  - Effects of gentle skin stimulation of various segmental areas on the micturition
      contractions of the urinary bladder were examined in anesthetized male rats. The
      bladder was expanded by infusing saline via urethral cannula until the bladder
      produced rhythmic micturition contractions as a consequence of rhythmic burst
      discharges of vesical pelvic efferent nerves. Gentle stimulation was applied for
      1 min by slowly rolling on top of skin with an elastomer "roller". Rolling on the
      perineal area inhibited both micturition contractions and pelvic efferent
      discharges during and after stimulation. Stimulation of the hindlimb, abdomen and
      forelimb inhibited micturition contractions after stimulation ended, in this
      order of effectiveness. During stimulation of the perineal skin, the reflex
      increase in pelvic efferent discharges in response to bladder distension to a
      constant pressure was also inhibited up to 45% of its control response. The
      inhibition of the micturition contractions induced by perineal stimulation was
      abolished, to a large extent by the opioid receptor antagonist naloxone and
      completely by severing cutaneous nerves innervating the perineal skin. We
      recorded unitary afferent activity from cutaneous branches of the pudendal nerve
      and found that the fibers excited by stimulation were low-threshold
      mechanoreceptive Abeta, Adelta and C fibers. Discharge rates of afferent C fibers
      (7.9 Hz) were significantly higher than those of Abeta (2.2 Hz) and Adelta (2.9
      Hz) afferents. The results suggest that low frequency excitation of low threshold
      cutaneous mechanoreceptive myelinated and unmyelinated fibers inhibits a vesico
      pelvic parasympathetic reflex, mainly via release of opioids, leading to
      inhibition of micturition contraction.

PMID- 22154754
TI  - Male reproduction is affected by RNA interference of period and timeless in the
      desert locust Schistocerca gregaria.
AB  - In all living organisms, behavior, metabolism and physiology are under the
      regulation of a circadian clock. The molecular machinery of this clock has been
      conserved throughout the animal kingdom. Besides regulating the circadian timing
      of a variety of processes through a central oscillating mechanism in the brain,
      these circadian clock genes were found to have a function in peripheral tissues
      in different insects. Here, we provide evidence that the circadian clock genes
      period (per) and timeless (tim) have a role in the male locust reproduction. A
      knockdown of either of the two genes has no effect on male sexual maturation or
      behavior, but progeny output in their untreated female copulation partners is
      affected. Indeed, the fertilization rates of the eggs are lower for females with
      a per or tim RNAi copulation partner as compared to the eggs deposited by females
      that mated with a control male. As the sperm content of the seminal vesicles is
      higher in per or tim knockdown males, we suggest that this phenotype could be
      caused by a disturbance of the circadian regulated sperm transfer in the male
      reproductive organs, or an insufficient maturation of the sperm after release
      from the testes.

PMID- 22154755
TI  - Ecdysone receptor and ultraspiracle proteins are tyrosine phosphorylated during
      adult development of silkmoths.
AB  - 20-hydroxy ecdysone (20E) is essential to promote adult development in diapausing
      silkmoth pupae. Increases in protein tyrosine/serine-phosphorylations observed
      soon after 20E administration supported the initial hypothesis that activation of
      receptor tyrosine kinase-ras-MAPK pathway could be responsible for the growth
      promoting effects of 20E. This report pertains to the high levels of protein
      tyrosine phosphorylations (PTP) that occurred later during the growth to
      differentiation transition because of its novelty and relevance to 20E dependence
      of adult development. Further analyses demonstrated that both ecdysone receptor
      (EcR) and ultraspiracle (USP), the two dimerizing partners of the functional
      ecdysone receptor, are tyrosine phosphorylated coincidental with high PTP.
      Enhanced PTP during growth to differentiation transition and concomitant tyrosine
      phosphorylation of EcR and USP was shown to occur in another silkmoth species
      pointing to the necessity of similar protein tyrosine phosphorylation pathways
      for adult development. Properly timed increases in tissue protein tyrosine kinase
      (PTK) activity could explain the enhancement of PTP in the wing epidermis of both
      the silkmoths. Thymidine incorporation measurements showed that cessation of DNA
      synthesis preceded the increase in PTK activity thus emphasizing a role for PTP
      in aspects of tissue physiology related to differentiative events rather than
      cell proliferation. Phosphatase and tyrosine kinase inhibitors (Tyrphostins) had
      minimal effects on adult wing development in vivo. However, the escape of the
      adult from the pupal case was blocked by a tyrphostin indicating the importance
      of PTKs in eclosion.

PMID- 22154756
TI  - Hydrogen peroxide as a mediator of vasorelaxation evoked by N-oleoylethanolamine
      and anandamide in rat small mesenteric arteries.
AB  - Hydrogen peroxide (H(2)O(2)) has been shown to participate in endothelium-derived
      hyperpolarising factor (EDHF)-mediated mechanisms. Vasorelaxation to the
      endocannabinoid-like N-oleoylethanolamine (OEA) and anandamide has been shown to
      be endothelium-dependent. Therefore, the principal aim was to investigate whether
      H(2)O(2) plays a role in vasorelaxation to endocannabinoids in rat mesenteric
      arteries. We have also investigated the effects of catalase on endothelium
      dependent relaxations and vascular responses to H(2)O(2). First- (G1) and third-
      (G3) order branches of the superior mesenteric artery from male, Wistar rats were
      mounted in a wire myograph, contracted with methoxamine, and concentration
      response curves to anandamide, OEA carbachol or H(2)O(2), were constructed. The
      influence of nitric oxide production and H(2)O(2) breakdown on these responses
      were then investigated using L-NAME (300 MUM), and catalase (1000 Uml(-1))
      respectively. In G1 mesenteric arteries, vasorelaxations to carbachol and
      H(2)O(2) were inhibited by L-NAME, but not by catalase. Responses to both
      anandamide and OEA were also unaffected by catalase. In G3 mesenteric arteries,
      endothelium-dependent relaxations to carbachol were modestly affected by L-NAME,
      unaffected by catalase alone, but their combination greatly inhibited
      vasorelaxation. Similarly, catalase inhibited vasorelaxation to anandamide and
      OEA, and combined treatment with L-NAME further reduced this response. In G1
      mesenteric arteries, vasorelaxation to H(2)O(2) is predominantly mediated by
      nitric oxide. We conclude that in G3 arteries H(2)O(2) activity contributes
      towards EDHF-type responses and vasorelaxation to endocannabinoids, either
      directly or indirectly. Given the association between vascular pathophysiology
      and H(2)O(2), these findings may provide a mechanism whereby disease states may
      influence responses to endocannabinoid and related mediators.

PMID- 22154757
TI  - Possible GABAergic mechanism in the neuroprotective effect of gabapentin and
      lamotrigine against 3-nitropropionic acid induced neurotoxicity.
AB  - Huntington's disease is a progressive neurodegenerative disorder that gradually
      reduces memory, cognitive skills and normal movements of affected individuals.
      Systemic administration of 3-Nitropropionic acid induces selective striatal
      lesions in rodents and non-human primates. Therefore, the present study has been
      designed to elucidate the comparative mechanistic profile of gabapentin,
      lamotrigine and their interactions with GABAergic modulators against 3
      Nitropropionic acid induced neurotoxicity. Systemic 3-Nitropropionic acid (10
      mg/kg) administration for 14 days significantly reduced body weight, locomotor
      activity, grip strength, oxidative defense (LPO, nitrite, SOD and catalase) and
      impaired mitochondrial complex enzyme (I, II, IV and MTT assay) activities in the
      striatum. 3-Nitropropionic acid treatment also increased TNF-alpha level in the
      striatum. Gabapentin (50 and 100 mg/kg) and lamotrigine (10, 20 and 40 mg/kg)
      treatments significantly restored behavioural, oxidative defense and
      mitochondrial complex enzyme activities and proinflammatory markers (TNF-alpha)
      as compared to 3-Nitropropionic acid treated group. Systemic picrotoxin (1 mg/kg)
      pretreatment with sub effective dose of gabapentin (50 mg/kg) or lamotrigine
      (20mg/kg) significantly attenuated their protective effect. Further, GABA (50
      mg/kg) and/or muscimol (0.05 mg/kg) pretreatment with sub effective dose
      gabapentin (50 mg/kg) and lamotrigine (20 mg/kg) significantly potentiated their
      protective effects which were significant as compared to their effect alone. The
      results of the present study suggest that a GABAergic mechanism is involved in
      the protective effect of gabapentin and lamotrigine against 3-Nitropropionic acid
      induced neurotoxicity.

PMID- 22154758
TI  - Association of mean platelet volume with DSM-IV major depression in a large
      community-based population: the MELEN study.
AB  - The relationship between major depression and increased platelet activity has
      been previously stated by several studies. This study sought to test the
      relationship between mean platelet volume (MPV)--an indicator of platelet
      activity--and major depression, in an adult Turkish population sample.
      Respondents were 2286 participants interviewed in a regional survey. The
      diagnosis of current (one month) major depression was made according to the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. MPV was
      measured along with total cholesterol, triglycerides, HDL-cholesterol, LDL
      cholesterol, BMI, and waist circumference. Two hundred eighty-nine participants
      (12.5%) were diagnosed as having major depression. Patients with major depression
      were found to have increased MPV levels in comparison with participants without
      depression (p = 0.001). After excluding the subjects with risk factors capable of
      influencing platelet activity, MPV was still found to be elevated in patients
      with major depression compared with non-depressed individuals (p < 0.01). Linear
      regression analysis revealed a significant independent association of major
      depression with MPV levels (r = 0.123; p = 0.001). According to the findings of
      this study, increased MPV (or platelet activation) is associated with current
      (one month) diagnosis of major depression. Future research should investigate the
      effect of depression treatment on MPV.

PMID- 22154759
TI  - Effects of perfluorooctanoic acid (PFOA) on expression of peroxisome proliferator
      activated receptors (PPAR) and nuclear receptor-regulated genes in fetal and
      postnatal CD-1 mouse tissues.
AB  - PPARs regulate metabolism and can be activated by environmental contaminants such
      as perfluorooctanoic acid (PFOA). PFOA induces neonatal mortality, developmental
      delay, and growth deficits in mice. Studies in genetically altered mice showed
      that PPARalpha is required for PFOA-induced developmental toxicity. In this
      study, pregnant CD-1 mice were dosed orally from GD1 to 17 with water or 5mg
      PFOA/kg to examine PPARalpha, PPARbeta, and PPARgamma expression and profile the
      effects of PFOA on PPAR-regulated genes. Prenatal and postnatal liver, heart,
      adrenal, kidney, intestine, stomach, lung, spleen, and thymus were collected at
      various developmental ages. RNA and protein were examined using qPCR and Western
      blot analysis. PPAR expression varied with age in all tissues, and in liver
      PPARalpha and PPARgamma expression correlated with nutritional changes as the
      pups matured. As early as GD14, PFOA affected expression of genes involved in
      lipid and glucose homeostatic control. The metabolic disruption produced by PFOA
      may contribute to poor postnatal survival and persistent weight deficits of CD-1
      mouse neonates.

PMID- 22154760
TI  - Spatial memory deficits in a virtual reality eight-arm radial maze in
      schizophrenia.
AB  - Learning and memory impairments are present in schizophrenia (SZ) throughout the
      illness course and predict psychosocial function. Abnormalities in prefrontal and
      hippocampal function are thought to contribute to SZ deficits. The radial arm
      maze (RAM) is a test of spatial learning and memory in rodents that relies on
      intact prefrontal and hippocampal function. The goal of the present study was to
      investigate spatial learning in SZ using a virtual RAM. Thirty-three subjects
      with SZ and thirty-nine healthy controls (HC) performed ten trials of a virtual
      RAM task. Subjects attempted to learn to retrieve four rewards each located in
      separate arms. As expected, subjects with SZ used more time and traveled more
      distance to retrieve rewards, made more reference (RM) and working memory (WM)
      errors, and retrieved fewer rewards than HC. It is important to note that the SZ
      group did learn but did not reach the level of HC. Whereas RM errors decreased
      across trials in the SZ group, WM errors did not. There were no significant
      relationships between psychiatric symptom severity and maze performance. To our
      knowledge, use of a virtual 8-arm radial maze task in SZ to assess spatial
      learning is novel. Impaired virtual RAM performance in SZ is consistent with
      studies that examined RAM performance in animal models of SZ. Results provide
      further support for compromised prefrontal and hippocampal function underlying WM
      and RM deficits in SZ. The virtual RAM task could help bridge preclinical and
      clinical research for testing novel drug treatments of SZ.

PMID- 22154761
TI  - Falling-incident detection and throughput enhancement in a multi-camera video
      surveillance system.
AB  - For most elderly, unpredictable falling incidents may occur at the corner of
      stairs or a long corridor due to body frailty. If we delay to rescue a falling
      elder who is likely fainting, more serious consequent injury may occur.
      Traditional secure or video surveillance systems need caregivers to monitor a
      centralized screen continuously, or need an elder to wear sensors to detect
      falling incidents, which explicitly waste much human power or cause inconvenience
      for elders. In this paper, we propose an automatic falling-detection algorithm
      and implement this algorithm in a multi-camera video surveillance system. The
      algorithm uses each camera to fetch the images from the regions required to be
      monitored. It then uses a falling-pattern recognition algorithm to determine if a
      falling incident has occurred. If yes, system will send short messages to someone
      needs to be noticed. The algorithm has been implemented in a DSP-based hardware
      acceleration board for functionality proof. Simulation results show that the
      accuracy of falling detection can achieve at least 90% and the throughput of a
      four-camera surveillance system can be improved by about 2.1 times.

PMID- 22154762
TI  - Design and synthesis of novel beta-diketo derivatives as HIV-1 integrase
      inhibitors.
AB  - A series of novel beta-diketo derivatives which combined the virtues of 1,3
      diketo, 1,2,3-triazole and polyhydroxylated aromatics moieties, were designed and
      synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated their
      inhibition to the strand transfer process of HIV-1 integrase. The result
      indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition
      to HIV-1 integrase, but dihydroxylated aromatic derivatives and corresponding
      methoxy aromatic derivatives appear little inhibition to HIV-1 integrase.

PMID- 22154763
TI  - The quest for the perfect MDS scoring system.

PMID- 22154764
TI  - Arteriolar insulin resistance in a rat model of polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the vascular dysfunction caused by insulin resistance
      in polycystic ovary syndrome (PCOS) and the effectiveness of vitamin D in an
      animal model. DESIGN: Controlled experimental animal study. SETTING: Animal
      laboratory at a university research institute. ANIMAL(S): Thirty female Wistar
      rats. INTERVENTION(S): Rats were divided into groups at age 21-28 weeks. Twenty
      of them were subjected to dihydrotestosterone (DHT) treatment (83 MUg/d); ten of
      them also received parallel vitamin D treatment (120 ng/100 g/wk). Oral glucose
      tolerance tests with insulin level measurements were performed. Gracilis
      arterioles were tested for their contractility as well as their nitric oxide (NO)
      dependent and insulin-induced dilation using pressure arteriography. MAIN OUTCOME
      MEASURE(S): Several physiologic parameters, glucose metabolism, and pressure
      arteriography. RESULT(S): DHT treatment increased the passive diameter of
      resistance arterioles, lowered norepinephrine-induced contraction (30.1 +/- 4.7%
      vs. 8.7 +/- 3.6%) and reduced acetylcholine-induced (122.0 +/- 2.9% vs. 48.0 +/-
      1.4%) and insulin-induced (at 30 mU/mL: 21.7 +/- 5.3 vs. 9.8 +/- 5.6%) dilation.
      Vitamin D treatment restored insulin relaxation and norepinephrine-induced
      contractility; in contrast, it failed to alter NO-dependent relaxation.
      CONCLUSION(S): In DHT-treated rats, in addition to metabolically proven insulin
      resistance, decreased insulin-induced vasorelaxation was observed and was
      improved by vitamin D treatment without affecting NO-dependent relaxation. The
      reduction in insulin-induced dilation of arterioles is an important as yet
      undescribed pathway of vascular damage in PCOS and might explain the clinical
      effectiveness of vitamin D treatment.

PMID- 22154766
TI  - Androgens and antimullerian hormone in mothers with polycystic ovary syndrome and
      their newborns.
AB  - OBJECTIVE: To explore the possible effect of metformin on maternal and fetal
      androgens and antimullerian hormone (AMH) levels at birth and to study the
      predictors of maternal and fetal AMH levels. DESIGN: Substudy of a randomized
      controlled trial (the PregMet study). SETTING: University hospital. PATIENT(S):
      Women with polycystic ovary syndrome (PCOS) and their newborns (n = 132).
      INTERVENTION(S): Metformin, 2,000 mg/daily, or placebo from the first trimester
      until delivery. MAIN OUTCOME MEASURE(S): Androgens and AMH levels in maternal
      venous serum and in umbilical vein and artery serum. RESULT(S): Except for the
      increased free testosterone index (FTI) in the umbilical artery in boys,
      metformin did not influence maternal or fetal androgens, or AMH levels. The
      maternal body mass index (BMI) was a negative and FTI a strong positive predictor
      of maternal AMH levels. Maternal androgens and AMH levels did not correlate to
      fetal gender. In girls, gestational age, birth weight, or maternal androgens did
      not correlate to the AMH levels. In boys, birth weight was negatively correlated
      to the AMH levels. CONCLUSION(S): Except for FTI, which was higher in boys,
      metformin had no impact on maternal or fetal androgen levels or the level of AMH.
      Fetal AMH, as a surrogate marker for ovarian development, was unaffected by
      maternal androgens. Birth weight and gestational age had no impact on AMH levels
      in girls; in boys, AMH probably reflects the physiologic variations due to birth
      weight. CLINICAL TRIAL REGISTRATION NUMBER: NCT00159536 (www.clinicaltrials.gov).

PMID- 22154765
TI  - Endometriosis-associated nerve fibers, peritoneal fluid cytokine concentrations,
      and pain in endometriotic lesions from different locations.
AB  - OBJECTIVE: To assess the relationship between endometriotic lesions with
      associated nerve fibers with both pain and peritoneal fluid (PF) cytokine
      concentrations based on lesion location. DESIGN: An observational study. SETTING:
      University hospital. PATIENT(S): Premenopausal women undergoing laparoscopy.
      INTERVENTION(S): The pain experienced by patients was recorded before surgery and
      ectopic endometrial tissue excised and matching PF collected during laparoscopy.
      Immunohistochemistry was performed on endometriotic tissue sections to identify
      nerve fibers and PF cytokine concentrations determined. MAIN OUTCOME MEASURE(S):
      The pain experienced by women with endometriosis, the lesion locations, and the
      prevalence and proximity of nerve fibers to endometriotic lesions, as well as the
      PF concentrations of multiple cytokines. RESULT(S): Lesions from the rectovaginal
      septum were significantly more likely to be associated with a nerve fiber and
      report more menstrual pain than lesions from other regions. The PF glycodelin
      concentrations were also significantly higher in samples with an endometriotic
      associated nerve. In peritoneal endometriotic lesions significantly more
      menstrual pain was reported when endometriotic lesions were associated with nerve
      fibers, although no difference was observed between the cytokine concentrations.
      Ovarian endometriotic lesions were rarely associated with nerve fibers.
      CONCLUSION(S): The presence of endometriosis-associated nerve fibers appear to be
      related to both the pain experienced by women with endometriosis and the
      concentration of PF cytokines; however, this association varies with the lesion
      location.

PMID- 22154767
TI  - Effect of maternal height and weight on risk of preterm birth in singleton and
      twin births resulting from in vitro fertilization: a retrospective cohort study
      using the Society for Assisted Reproductive Technology Clinic Outcome Reporting
      System.
AB  - OBJECTIVE: To examine the effect of height, weight, and body mass index (BMI) on
      the risk of preterm birth of singleton and twin pregnancies conceived by vitro
      fertilization (IVF). DESIGN: Retrospective cohort study using 2006-2008 data from
      the Society for Reproductive Technology Clinic Outcome Reporting System (SART
      CORS). SETTING: SART-associated assisted reproductive technology programs.
      PATIENT(S): 56,556 singleton and 23,804 twin live births resulting from fresh
      nondonor IVF cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of
      very early preterm (VEPTB; <28 weeks), very preterm (VPTB; <32 weeks), and
      preterm birth (<37 weeks) births. RESULT(S): In both singleton and twin births,
      increased maternal height was associated with a decreased risk of preterm birth.
      Maternal overweight and obesity were associated with significantly increased risk
      of VEPTB and VPTB in twin pregnancies. For very obese women (BMI > 35 kg/m(2))
      twins were associated with a threefold increased risk of VEPTB (6.1% vs. 2.0%)
      and a twofold increased risk of VPTB (11.5% vs. 5.9%) compared with women of
      normal weight (BMI 18.4-24.9 kg/m(2)). CONCLUSION(S): Obesity and short stature
      significantly increase the risk of VEPTB and VPTB in twins conceived by IVF.

PMID- 22154768
TI  - The cost and disease burden of pneumonia in general practice in Australia.
AB  - It is important to have an understanding of the cost and disease burden of
      pneumonia in the community to help evaluate future prevention efforts. We
      examined general practitioner (GP) visits (and estimated the related costs) where
      pneumonia was managed from data collected in a continuous national survey, data
      period April 2006-March 2009. The majority of visits were standard length surgery
      consultations, with medication prescribed for 63%, imaging requested for 29%, and
      pathology for 10% of pneumonia problems managed. We estimated an average cost per
      GP visit of A$57.05 after adjusting for the number of problems managed. An annual
      average of 343,000 GP visits for pneumonia was estimated in Australia at cost of
      ~A$20 million per year.

PMID- 22154769
TI  - Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in
      healthy adults >=60 years of age.
AB  - BACKGROUND: Incidence and severity of herpes zoster (HZ) and postherpetic
      neuralgia increase with age, associated with age-related decrease in immunity to
      varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated
      substantial protection against HZ; this study examined impact of a second dose of
      ZV. METHODS: Randomized, double-blind, multicenter study with 210 subjects >=60
      years old compared immunity and safety profiles after one and two doses of ZV,
      separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV
      interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay and VZV
      glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse
      experiences (AEs) were recorded on a standardized Vaccination Report Card.
      RESULTS: No serious vaccine-related AEs occurred. VZV IFN-gamma ELISPOT geometric
      mean count (GMC) of spot-forming cells per 10(6) peripheral blood mononuclear
      cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2
      and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2,
      GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not
      change during the study. The peak ELISPOT response occurred ~2 weeks after each
      ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher
      than in the placebo group at 6 weeks after each dose. Correlation between the IFN
      gamma ELISPOT and gpELISA assays was poor. CONCLUSIONS: ZV was generally well
      tolerated and immunogenic in adults >=60 years old. A second dose of ZV was
      generally safe, but did not boost VZV-specific immunity beyond levels achieved
      postdose 1.

PMID- 22154770
TI  - Streptococcus pneumoniae pep27 mutant as a live vaccine for serotype-independent
      protection in mice.
AB  - Streptococcus pneumoniae (pneumococcus) is responsible for significant morbidity
      and mortality in worldwide. After introduction of current pneumococcal vaccines,
      a marked decrease in the incidence of pneumococcal disease was observed.
      Unfortunately, serotype shifts in carriage and disease, including capsular switch
      and presence of antimicrobial resistance, have been found. Here we report live
      attenuated vaccine strain which is avirulent and can protect from systemic and
      mucosal pneumococcal diseases. Pep27, an autolysis-inducing factor of S.
      pneumoniae is known to mediate LytA-dependent and -independent lysis and it was
      thus expected to effect virulence. The loss of Pep27 had a much larger than
      expected decrease in virulence and has made the Pep27 mutant strain sufficiently
      avirulent to be used as a live vaccine. The pep27 mutation unexpectedly had lower
      level of capsular polysaccharide than the wild type (type 2, D39) strain.
      Moreover, the pep27 mutant showed rapid clearance by 24 h post intranasal
      infection, and was not detected in lung and blood suggesting that mutant could
      not invade into the tissue. Even when 2*10(8)CFU were injected intravenously the
      mutant was not detected in the blood or brain after 4 h. Whereas 4 h after
      injection of 6*10(6) CFU of the wild type parent D39 strain, bacteremia was
      readily detected. Two dose intranasal immunizations with the live pep27 mutant in
      the absence of adjuvant elicited IgG antibody and serotype-independent protection
      against lethal intranasal challenge. Thus Pep27 was essential for virulence, and
      intranasal immunization with the pep27 mutant could provide protective immunity.

PMID- 22154771
TI  - Lactococcus lactis-based vaccines from laboratory bench to human use: an
      overview.
AB  - Developing effective vaccines is an important weapon in the battle against
      potential pathogens and their evolving antibiotic resistance trends. Several
      vaccine delivery vectors have been investigated among which the generally
      regarded as safe (GRAS) Lactococcus lactis has a distinguished position. In this
      review, different factors affecting the efficacy of L. lactis-based vaccines are
      discussed. In addition, the issues of biological containment and pharmaceutical
      quality assurance of L. lactis vaccines are highlighted. These issues are
      critical for the success of medical translation of L. lactis-based vaccines from
      research laboratories to clinical use by ensuring consistent manufacturing of
      safe and efficacious vaccines.

PMID- 22154772
TI  - Influenza vaccination among healthcare personnel after pandemic influenza H1N1.
AB  - The purpose of this study was to evaluate the coverage rates for influenza
      vaccination among health-care personnel (HCP), and if the reasons for accepting
      influenza vaccine by HCP and the frequency of vaccine-related adverse events
      (AEs) in 2010-2011 were different compared to 2009-2010. The AEs were detected by
      telephoning the worker one week after the vaccination. The coverage for seasonal
      vaccination in 2009-2010 was 31.0%, whereas that for 2009 pandemic influenza
      (H1NI) was 22.2% and 24.4% (p<0.05) in 2010-2011. The most frequent reason for
      being vaccinated during the three campaigns was to "protect my health". Over
      80.5% of the HCP reported 2009 pandemic influenza (H1N1) vaccine-related AEs
      compared to the 25.3% and 25.4% reporting seasonal vaccine-related AEs in 2009
      2010 and 2010-2011 respectively (p<0.05). None of the AEs were severe. Specific
      measures should be implemented in our country to recover and improve poor
      vaccination coverage.

PMID- 22154773
TI  - Introduction of human papillomavirus vaccination in Nordic countries.
AB  - INTRODUCTION: Cervical screening has helped decrease the incidence of cervical
      cancer, but the disease remains a burden for women. Human Papillomavirus (HPV)
      vaccination is now a promising tool for control of cervical cancer. Nordic
      countries (Denmark, Finland, Greenland, Iceland, Norway and Sweden) are
      relatively wealthy with predominantly publicly paid health care systems. The aim
      of this paper was to provide an update of the current status of introduction of
      HPV vaccine into the childhood vaccination programs in this region. METHODS: Data
      on cervical cancer, cervical screening programs, childhood immunization and HPV
      vaccination programs for Nordic countries were searched via PubMed and various
      organizations. We furthermore contacted selected experts for information.
      RESULTS: The incidence of cervical cancer is highest in Greenland (25 per
      100,000, age standardized, World Standard Population, ASW) and lowest in Finland
      (4 per 100,000 ASW) and rates in the other Nordic countries vary between 7 and 11
      per 100,000 ASW. Greenland and Denmark were first to introduce HPV vaccination,
      followed by Norway. Vaccination programs are underway in Sweden and Iceland,
      while Finland has just recently recommended introduction of vaccination. HPV
      vaccination has been intensively debated, in particular in Denmark and Norway.
      DISCUSSION: In Nordic countries with a moderate risk of cervical cancer and a
      publicly paid health care system, the introduction of HPV vaccination was a
      priority issue. Many players became active, from the general public to health
      professionals, special interest groups, and the vaccine manufacturers. These
      seemed to prioritize different health care needs and weighed differently the
      uncertainty about the long-term effects of the vaccine. CONCLUSION: HPV
      vaccination posed a pressure on public health authorities to consider the
      evidence for and against it, and on politicians to weigh the wish for cervical
      cancer protection against other pertinent health issues.

PMID- 22154774
TI  - Codon changed immobilization antigen (iAg), a potent DNA vaccine in fish against
      Cryptocaryon irritans infection.
AB  - The immobilization antigen (iAg) DNA sequence from Chiayi isolate of Cryptocaryon
      irritans was computationally reviewed to replace the stop codons with suitable
      amino acids and its GC content was intensified. The plasmid construct comprising
      the codon changed iAg (optiAg/optimized iAg) was successfully expressed in the
      bacterial strain BL21 and also in grouper fin cells (GF-1). Results of
      immobilization assay, ELISA and western blot of C. irritans theront and
      recombinant iAg by grouper antiserum against optiAg DNA indicated that the codon
      changed iAg retains the native conformation. The DNA vaccine construct pcDNA3.1
      optiAg was encapsulated in water-oil-water triple layer emulsions measuring 19
      MUm diameters and was used for the immunization experiment. In trial I
      experiment, grouper fish were immunized twice via intramuscular injection with
      the pcDNA3.1-optiAg and were challenged with C. irritans at 8-day post
      immunization (dpi), which resulted in 46% relative percent survival (RPS). In
      trial II, single immunization with pcDNA3.1-optiAg boosted with recombinant iAg
      protein, resulted in 40% RPS. The data from this study reveal that codon change
      in iAg not only accomplished the expression of iAg protein in both prokaryotic
      and eukaryotic cell systems, but also optiAg was proved as immunogenic due to the
      protection it confers to the immunized fish against C. irritans infection. Hence,
      it is concluded that iAg can be a potent DNA vaccine in fish against infection of
      the ciliated protozoan, C. irritans.

PMID- 22154775
TI  - Bitten by the "flying" tree snake, Chrysopelea paradisi.
AB  - BACKGROUND: The paradise tree snake, Chrysopelea paradisi, is a rear-fanged
      colubrid. Like other members of the genus Chrysopelea, it is able to glide
      through the air, and thus, is commonly known as a "flying snake." There are few
      documented effects of its bite on humans. CASE REPORT: A 16-year-old military
      college student presented to the Emergency Department (ED) of an urban teaching
      hospital 2 h after being bitten by C. paradisi. There were multiple bite marks
      and the patient reported moderate pain on the left index finger. There was no
      evidence of significant local or systemic envenomation. A transient prolonged
      coagulation profile and raised creatine kinase level were noted. CONCLUSION: The
      full effects of a bite from C. paradisi remain uncharacterized. This case
      featured only mild local effect. After the administration of first aid, non
      sedating analgesia, anti-tetanus toxoid injection, and broad-spectrum antibiotic
      coverage, a short stay in the ED observation ward with regular monitoring of
      vital signs and serial wound inspection are recommended. More effort is required
      to increase awareness of the prevention and management of snakebite with equal
      emphasis on conservation of wildlife and their natural habitat.

PMID- 22154777
TI  - An adenosine-independent index of stenosis severity from coronary wave-intensity
      analysis: a new paradigm in coronary physiology for the cath lab?

PMID- 22154778
TI  - Sulfur dioxide induced programmed cell death in Vicia guard cells.
AB  - Sulfur dioxide (SO(2)) induced nuclear condensation and nuclear fragmentation and
      rapid loss of guard cell viability in detached epidermis of Vicia leaves at
      concentrations of 1 mM and higher (3 h exposure). Caspase inhibitors Z-Asp-CH(2)
      DCB (0.1 mM) and TLCK (0.1 mM) markedly suppressed SO(2)-induced cell death. The
      typical nuclear morphological changes and the inhibition effects of caspase
      inhibitors suggest the activation of a programmed cell death (PCD) pathway. SO(2)
      induced cell death can be blocked by either antioxidants (0.1 mM AsA or 200 U/mL
      CAT) or Ca(2+) antagonists (0.1mM EGTA or LaCl(3)). AsA and CAT also blocked
      SO(2)-induced ROS production and [Ca(2+)](cyt) increase. However, EGTA and
      LaCl(3) can inhibit SO(2)-induced [Ca(2+)](cyt) increase, but cannot suppress
      SO(2)-induced ROS production. Our results indicate that high concentrations of
      SO(2) induce guard cell death via a PCD pathway through ROS mediating
      [Ca(2+)](cyt) elevation, which causes harmful effects to plants.

PMID- 22154776
TI  - Hemoglobin directs macrophage differentiation and prevents foam cell formation in
      human atherosclerotic plaques.
AB  - OBJECTIVES: The purpose of this study was to examine selective macrophage
      differentiation occurring in areas of intraplaque hemorrhage in human
      atherosclerosis. BACKGROUND: Macrophage subsets are recognized in
      atherosclerosis, but the stimulus for and importance of differentiation programs
      remain unknown. METHODS: We used freshly isolated human monocytes, a rabbit
      model, and human atherosclerotic plaques to analyze macrophage differentiation in
      response to hemorrhage. RESULTS: Macrophages characterized by high expression of
      both mannose and CD163 receptors preferentially exist in atherosclerotic lesions
      at sites of intraplaque hemorrhage. These hemoglobin (Hb)-stimulated macrophages,
      M(Hb), are devoid of neutral lipids typical of foam cells. In vivo modeling of
      hemorrhage in the rabbit model demonstrated that sponges exposed to red cells
      showed an increase in mannose receptor-positive macrophages only when these cells
      contained Hb. Cultured human monocytes exposed to Hb:haptoglobin complexes, but
      not interleukin-4, expressed the M(Hb) phenotype and were characterized by their
      resistance to cholesterol loading and up-regulation of ATP-binding cassette (ABC)
      transporters. M(Hb) demonstrated increased ferroportin expression, reduced
      intracellular iron, and reactive oxygen species (ROS). Degradation of ferroportin
      using hepcidin increased ROS and inhibited ABCA1 expression and cholesterol
      efflux to apolipoprotein A-I, suggesting reduced ROS triggers these effects.
      Knockdown of liver X receptor alpha (LXRalpha) inhibited ABC transporter
      expression in M(Hb) and macrophages differentiated in the antioxidant superoxide
      dismutase. Last, LXRalpha luciferase reporter activity was increased in M(Hb) and
      significantly reduced by overnight treatment with hepcidin. Collectively, these
      data suggest that reduced ROS triggers LXRalpha activation and macrophage reverse
      cholesterol transport. CONCLUSIONS: Hb is a stimulus for macrophage
      differentiation in human atherosclerotic plaques. A decrease in macrophage
      intracellular iron plays an important role in this nonfoam cell phenotype by
      reducing ROS, which drives transcription of ABC transporters through activation
      of LXRalpha. Reduction of macrophage intracellular iron may be a promising avenue
      to increase macrophage reverse cholesterol transport.

PMID- 22154779
TI  - Questioning the legitimacy of rigid bronchoscopy as a tool for establishing the
      diagnosis of a bronchial foreign body.
AB  - OBJECTIVES: Rigid bronchoscopy (RB) is the principal method used for the
      extraction of a tracheo-bronchial foreign body (FB), but its use as a diagnostic
      tool implies a certain rate of negative exams, exposing the child to the risk of
      procedure and anesthesia-related complications. Technological progress has
      improved the accuracy and availability of non-invasive modalities, such as CT
      scan and fluoroscopy. Our aim is to review our experience in the routine use of
      bronchoscopy for a suspected FB aspiration, and evaluate the adequacy of our
      current attitude in light of these alternatives. METHODS: We performed a
      retrospective review of cases where bronchoscopy was used in the management of a
      suspected airway FB, and analysis of the correlation between the clinical and
      radiological data and the bronchoscopy's results. In addition we reviewed the
      literature concerning the use of RB and alternative means of diagnosis such as CT
      scan, fluoroscopy and flexible bronchoscopy. RESULTS: Thirty-two patients
      underwent bronchoscopy to rule out a FB aspiration under general anesthesia. No
      FB was found in 8 cases (25%). Cough and a history of choking were the most
      sensitive parameters (sensitivity 100% and 80% respectively), but had a low
      specificity. Stridor was the most specific sign (88% specificity), but was not
      sensitive. Chest radiography had 25% sensitivity, and 62.5% specificity. Flexible
      bronchoscopy changed the management in 22% of cases, sparing RB. CONCLUSIONS:
      Basing the decision to perform RB solely on the clinical findings and chest
      radiography entails a 25% rate or more of negative exams. CT scan appears to be
      the most accurate non-invasive tool for ruling out the presence of a FB but its
      use cannot be systematic due to its complexity and the risks of exposure to
      radiation. Digital substraction fluoroscopy is a safe and simple mean to confirm
      the presence of air trapping generated by a bronchial obstruction, but it is not
      sensitive enough to definitively rule out a FB. We propose a stepwise approach
      using fluoroscopy or possibly flexible bronchoscopy under sedation, in order to
      reduce the number of negative RBs while restricting the use of the CT scan.

PMID- 22154780
TI  - Low extracellular pH stimulates the production of IL-1beta by human monocytes.
AB  - The development of acidic environments is a hallmark of inflammatory processes of
      different etiology. We have previously shown that transient exposure to acidic
      conditions, similar to those encountered in vivo, induces the activation of
      neutrophils and the phenotypic maturation of dendritic cells. We here report that
      extracellular acidosis (pH 6.5) selectively stimulates the production and the
      secretion of IL-1beta by human monocytes without affecting the production of TNF
      alpha, IL-6 and the expression of CD40, CD80, CD86, and HLA-DR. Stimulation of IL
      1beta production by pH 6.5-treated monocytes was shown to be dependent on caspase
      1 activity, and it was also observed using peripheral blood mononuclear cells
      instead of isolated monocytes. Contrasting with the results in monocytes, we
      found that pH 6.5 did not stimulate any production of IL-1beta by macrophages.
      Changes in intracellular pH seem to be involved in the stimulation of IL-1beta
      production. In fact, monocytes cultured at pH 6.5 undergo a fall in the values of
      intracellular pH while the inhibitor of the Na+/H+ exchanger, 5-(N-ethyl-N
      isopropyl)amiloride induced both, a decrease in the values of intracellular pH
      and the stimulation of IL-1beta production. Real time quantitative PCR assays
      indicated that monocytes cultured either at pH 6.5 or in the presence of 5-(N
      ethyl-N-isopropyl)amiloride expressed higher levels of pro-IL-1beta mRNA
      suggesting that low values of intracellular pH enhance the production of IL
      1beta, at least in part, by stimulating the synthesis of its precursor.

PMID- 22154781
TI  - Outbreak of adenovirus serotype 8 conjunctivitis in preterm infants in a neonatal
      intensive care unit.
AB  - BACKGROUND: Adenovirus keratoconjunctivitis outbreaks have rarely been reported
      in preterm infants. An outbreak of adenovirus conjunctivitis occurred between 15
      January and 25 February at a neonatal intensive care unit of a university
      hospital in Turkey. AIM: To describe the evolution, investigation and management
      of the outbreak. METHODS: Adenovirus type 8 was identified in 14 samples by
      polymerase chain reaction analysis. A case-control study was performed to
      determine the risk factors. FINDINGS: Fifteen preterm neonates, five healthcare
      workers (HCWs) and four parents suffered from conjunctivitis signs such as
      lacrimation, swelling and redness of the eye. A retinopathy of prematurity (ROP)
      examination was found to be the most important risk factor for adenovirus
      conjunctivitis (odds ratio: 17.5; 95% confidence interval: 1.9-163.0; P=0.012).
      The eyelid speculum (blepharostat) used during the ROP examination was not
      sterilized between each patient and was found to be the cause of contamination.
      CONCLUSION: The outbreak was controlled by measures such as barrier precautions,
      hand hygiene, sterilization of the blepharostat, suspending patient transfer to
      other units, and excluding infected HCWs for at least 15 days.

PMID- 22154782
TI  - Response to: Buehlmann et al. 'Effectiveness of a new decolonisation regimen for
      eradication of extended-spectrum beta-lactamase-producing Enterobacteriaceae'.

PMID- 22154784
TI  - What is repeated in ALS and FTLD.

PMID- 22154785
TI  - A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders
      of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum:
      a gene identification study.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar
      degeneration (FTLD) are extremes of a clinically, pathologically, and genetically
      overlapping disease spectrum. A locus on chromosome 9p21 has been associated with
      both disorders, and we aimed to identify the causal gene within this region.
      METHODS: We studied 305 patients with FTLD, 137 with ALS, and 23 with concomitant
      FTLD and ALS (FTLD-ALS) and 856 controls from Flanders (Belgium); patients were
      identified from a hospital-based cohort and were negative for mutations in known
      FTLD and ALS genes. We also examined the family of one patient with FTLD-ALS
      previously linked to 9p21 (family DR14). We analysed 130 kbp at 9p21 in
      association and segregation studies, genomic sequencing, repeat genotyping, and
      expression studies to identify the causal mutation. We compared genotype
      phenotype correlations between mutation carriers and non-carriers. FINDINGS: In
      the patient-control cohort, the single-nucleotide polymorphism rs28140707 within
      the 130 kbp region of 9p21 was associated with disease (odds ratio [OR] 2.6, 95%
      CI 1.5-4.7; p=0.001). A GGGGCC repeat expansion in C9orf72 completely co
      segregated with disease in family DR14. The association of rs28140707 with
      disease in the patient-control cohort was abolished when we excluded GGGGCC
      repeat expansion carriers. In patients with familial disease, six (86%) of seven
      with FTLD-ALS, seven (47%) of 15 with ALS, and 12 (16%) of 75 with FTLD had the
      repeat expansion. In patients without known familial disease, one (6%) of 16 with
      FTLD-ALS, six (5%) of 122 with ALS, and nine (4%) of 230 with FTLD had the repeat
      expansion. Mutation carriers primarily presented with classic ALS (10 of 11
      individuals) or behavioural variant FTLD (14 of 15 individuals). Mean age at
      onset of FTLD was 55.3 years (SD 8.4) in 21 mutation carriers and 63.2 years
      (9.6) in 284 non-carriers (p=0.001); mean age at onset of ALS was 54.5 years
      (9.9) in 13 carriers and 60.4 years (11.4) in 124 non-carriers. Postmortem
      neuropathological analysis of the brains of three mutation carriers with FTLD
      showed a notably low TDP-43 load. In brain at postmortem, C9orf72 expression was
      reduced by nearly 50% in two carriers compared with nine controls (p=0.034). In
      familial patients, 14% of FTLD-ALS, 50% of ALS, and 62% of FTLD was not accounted
      for by known disease genes. INTERPRETATION: We identified a pathogenic GGGGCC
      repeat expansion in C9orf72 on chromosome 9p21, as recently also reported in two
      other studies. The GGGGCC repeat expansion is highly penetrant, explaining all of
      the contribution of chromosome 9p21 to FTLD and ALS in the Flanders-Belgian
      cohort. Decreased expression of C9orf72 in brain suggests haploinsufficiency as
      an underlying disease mechanism. Unidentified genes probably also contribute to
      the FTLD-ALS disease spectrum. FUNDING: Full funding sources listed at end of
      paper (see Acknowledgments).

PMID- 22154786
TI  - Mitral valve reconstruction in Barlow disease: long-term echographic results and
      implications for surgical management.
AB  - OBJECTIVE: Owing to the complexity of the underlying lesions, Barlow disease
      remains a challenge for surgeons performing mitral valve repair. We aimed to
      assess whether our most recent results involving several surgeons were comparable
      with those of a previous experience in which mitral valve repair was performed by
      a more limited group of surgeons. METHODS: From September 2000 to January 2007,
      200 patients with Barlow disease (135 men and 65 women; mean age, 56 +/- 13
      years) were referred to our institution for surgical treatment of their mitral
      regurgitation. We retrospectively analysed the mitral lesions characteristics,
      the surgical techniques used, and clinical outcomes. Follow-up echocardiograms
      were biannually reviewed. RESULTS: Lesions comprised annular dilatation, excess
      tissue, and leaflet prolapse in all cases. The most frequent prolapsed segments
      were P2 (88.5%; n = 177) and A2 (55.5%; n = 111). Annular calcifications and
      restrictive valvular motion were associated in 20% (n = 40). Repair was feasible
      in 94.7% (n = 179/189) of non-redo interventions. Immediate postoperative
      echocardiography showed residual mitral regurgitation greater than 1+ in 6 cases;
      these patients were all reoperated on within the next months. Operative mortality
      was 1.5% (n = 3). Mean follow-up was 77.5 +/- 25.6 months. At 8 years
      postoperatively, overall survival was 88.6% +/- 3.1%, freedom from reintervention
      was 95.3% +/- 1.7%, and freedom from late recurrent moderate mitral regurgitation
      (>2+) was 90.2% +/- 3.1% CONCLUSIONS: Provided that the fundamental principles of
      mitral valve reconstruction are respected, the surgical techniques are highly
      reproducible with good long-term results, similar to those published during the
      pioneering phase of this surgery.

PMID- 22154787
TI  - Pulmonary root translocation in malposition of great arteries repair allows right
      ventricular outflow tract growth.
AB  - OBJECTIVE: Optimal surgical treatment of patients with transposition of the great
      arteries (TGA), ventricular septal defect (VSD), and pulmonary stenosis (PS)
      remains a matter of debate. This study evaluated the clinical outcome and right
      ventricle outflow tract performance in the long-term follow-up of patients
      subjected to pulmonary root translocation (PRT) as part of their surgical repair.
      METHODS: From April 1994 to December 2010, we operated on 44 consecutive patients
      (median age, 11 months). All had malposition of the great arteries as follows:
      TGA with VSD and PS (n = 33); double-outlet right ventricle with subpulmonary VSD
      (n = 7); double-outlet right ventricle with atrioventricular septal defect (n =
      1); and congenitally corrected TGA with VSD and PS (n = 3). The surgical
      technique consisted of PRT from the left ventricle to the right ventricle after
      construction of an intraventricular tunnel that diverted blood flow from the left
      ventricle to the aorta. RESULTS: The mean follow-up time was 72 +/- 52.1 months.
      There were 3 (6.8%) early deaths and 1 (2.3%) late death. Kaplan-Meier survival
      was 92.8% and reintervention-free survival was 82.9% at 12 years. Repeat
      echocardiographic data showed nonlinear growth of the pulmonary root and good
      performance of the valve at 10 years. Only 4 patients required reinterventions
      owing to right ventricular outflow tract problems. CONCLUSIONS: PRT is a good
      surgical alternative for treatment of patients with TGA complexes, VSD, and PS,
      with acceptable operative risk, high long-term survivals, and few
      reinterventions. Most patients had adequate pulmonary root growth and
      performance.

PMID- 22154788
TI  - Staged percutaneous coronary intervention and minimally invasive valve surgery:
      results of a hybrid approach to concomitant coronary and valvular disease.
AB  - BACKGROUND: We compared a hybrid approach combining staged percutaneous coronary
      intervention (PCI) and minimally invasive valve surgery with concurrent valve
      surgery plus bypass via a median sternotomy approach. METHODS: We retrospectively
      evaluated 65 consecutive patients with coronary disease and surgical valvular
      heart disease who underwent planned PCI followed within 60 days by minimally
      invasive valve surgery, and we compared them with 52 matched control patients who
      underwent conventional bypass grafting and valve surgery. RESULTS: There were no
      in-hospital deaths in the hybrid group, compared with 2 (3.8%) observed in the
      matched group (P = .11). Death, renal failure, or stroke occurred in 1 (1.5%) in
      the hybrid group versus 15 (28.8%) in the conventional group (P = .001). The
      median number of days between PCI and surgery was 24 (interquartile range, 2.5
      37). At surgery, 23 hybrid patients were receiving both aspirin and clopidogrel;,
      18, clopidogrel alone; 4, aspirin alone; and 22 stopped the antiplatelet agents 5
      days before the operation. Intensive care unit hours and total hospital length of
      stay, including PCI stay for the hybrid group, were less in the hybrid group (P =
      .001 for both comparisons). In the hybrid group, average blood use was 1.6 +/-
      1.6 U per patient versus 1.9 +/- 2.4 U per patient with conventional surgery (P =
      .35. There were no reoperations for postoperative bleeding in the hybrid group
      compared with 2 (3.8%) in the conventional group (P = .43). CONCLUSIONS: Staged
      PCI with minimally invasive valve surgery may offer an alternative to coronary
      bypass grafting with concurrent valve surgery and should be tested prospectively.

PMID- 22154789
TI  - Magnetic resonance imaging versus echocardiography to ascertain the regression of
      left ventricular hypertrophy after bioprosthetic aortic valve replacement:
      results of the REST study.
AB  - OBJECTIVES: To compare the decrease in left ventricular mass index (LVMI) by
      magnetic resonance imaging (MRI) versus transthoracic echocardiography (TTE)
      after aortic valve replacement (AVR) for severe aortic stenosis with Epic and
      Epic Supra stented porcine bioprostheses (St Jude Medical, Inc, St Paul, Minn).
      METHODS: This prospective multicenter study enrolled 149 patients who underwent
      AVR between January 2006 and February 2008. TTE and cardiac MRI measurements of
      LVMI were made at baseline and at 6 months of follow-up and were compared.
      Changes in mean pressure gradients were examined using TTE. RESULTS: TTE
      measurements of LVMI were 48% to 63% higher than the MRI measurements. A decrease
      in LVMI from 137 +/- 32 to 95 +/- 16 g/m(2) with the Epic and from 139 +/- 29 to
      104 +/- 28 g/m(2) with the Epic Supra valves (P < .0001 for both comparisons) was
      measured by TTE. Cardiac MRI revealed decreases in LVMI from 84 +/- 20 to 64 +/-
      12 g/m(2) and from 86 +/- 27 to 64 +/- 17 g/m(2) with the Epic and Epic Supra
      valves, respectively (P < .0001 for both comparisons). TTE revealed a significant
      regression of mean pressure gradients from 51.6 +/- 15.3 to 15.5 +/- 5.2 mm Hg
      with the Epic and from 46.7 +/- 19.4 to 17.9 +/- 12.8 mm Hg with the Epic supra
      (P < .0001 for both comparisons). CONCLUSIONS: A significant decrease in LVMI was
      measured after AVR with all sizes of both bioprosthetic models. Because of the
      overestimation of the decrease in LVMI by the Devereux formula, as well as the
      higher accuracy and reproducibility of cardiac MRI measurements, the latter
      should be preferred to TTE. An ultimate validation of this thesis could only be
      done comparing each of these modalities with pathologic examination.

PMID- 22154790
TI  - Effects of gender and ethnicity on outcomes after aortic valve replacement.
AB  - OBJECTIVE: To evaluate the clinical outcomes after aortic valve replacement or
      aortic valve replacement and coronary artery bypass grafting in a large
      contemporary population, and to determine if outcomes are associated with patient
      ethnicity and gender status. METHODS: Using the Massachusetts Cardiac Surgery
      Database, we identified 6809 adults aged 18 years or older who had undergone
      isolated aortic valve replacement or aortic valve replacement and coronary artery
      bypass grafting in all non-federal acute-care Massachusetts hospitals from 2002
      to 2008. Univariate and multivariate logistic regression analyses were used to
      identify differences in patient characteristics, major morbidity, and 30-day and
      1-year mortality between men (n=4043) and women (n=2766) and between whites
      (n=6481) and nonwhites (n=328). RESULTS: The unadjusted 30-day mortality rate was
      2.6% for the men and 3.1% for the women (P=.296) and 2.8% for whites and 3.7% for
      nonwhites (P=.342). In adjusted logistic regression models, the 30-day mortality
      was not different between the female and male patients (odds ratio, 0.88; 95%
      confidence interval, 0.26-3.02, P=.84) nor between the nonwhites and whites (odds
      ratio, 1.57; 95% confidence interval, 0.45-5.44; P=.48). The incidence of
      postoperative stroke was greater in women (3.0% women and 2.2% men, P=.031), and
      the incidence of postoperative myocardial infarction (10.9% women and 13.6% men;
      P=.001) and septicemia (1.2% women and 2.0% men; P=.009) was greater in men.
      CONCLUSIONS: Ethnicity and gender were not associated with greater 30-day and 1
      year mortality after aortic valve replacement or aortic valve replacement and
      coronary artery bypass grafting. Differences in postoperative outcomes were not
      observed between ethnic groups.

PMID- 22154791
TI  - Utility of endobronchial ultrasound-guided mediastinal lymph node biopsy in
      patients with non-small cell lung cancer.
AB  - OBJECTIVE: Invasive mediastinal biopsy is often necessary in the evaluation of
      non-small cell lung cancer (NSCLC), and mediastinoscopy has long been considered
      the reference standard. However, the emergence of endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) has resulted in controversy
      regarding it represents a suitable replacement for mediastinoscopy. We chose to
      determine the utility of EBUS-TBNA in evaluating the mediastinum in patients with
      NSCLC. METHODS: The present study was a retrospective review of a prospective
      database of consecutive patients with NSCLC who underwent EBUS-TBNA for
      mediastinal evaluation from 2009 to 2011. The sensitivity, specificity, negative
      predictive value, and accuracy of EBUS-TBNA are reported. Also reported are the
      size of the lymph nodes biopsied and the number of instances in which EBUS-TBNA
      obviated the need for cervical mediastinoscopy. RESULTS: A total of 73 patients
      had a total of 140 mediastinal stations biopsied using EBUS-TBNA. Of the 73
      patients, 30 had benign findings and underwent surgical resection, 1 of whom was
      found to have stage N2 disease. Of the remaining patients, 42 had a positive
      result and 1 had nondiagnostic biopsy findings for which malignancy was confirmed
      by mediastinoscopy. Mediastinoscopy would have changed the tumor stage and
      treatment planning in only 2 (2.7%) of the 73 patients. Overall, EBUS-TBNA had a
      sensitivity of 95%, a specificity of 100%, a negative predictive value of 94%,
      and an accuracy of 97%. CONCLUSIONS: EBUS-TBNA might be a feasible option for
      most patients with NSCLC for whom histologic assessment of the mediastinum is
      necessary. The rates of nondiagnostic and false-negative biopsy findings using
      EBUS-TBNA were low, small subcentimeter nodes could be routinely biopsied, and
      most patients with a radiographically positive mediastinum had their disease
      pathologically confirmed.

PMID- 22154793
TI  - Cardiac magnetic resonance imaging is more diagnostic than 2-dimensional
      echocardiography in determining the presence of bicuspid aortic valve.
AB  - OBJECTIVE: This study compares 2-dimensional, transthoracic echocardiography with
      cardiac magnetic resonance imaging in the preoperative identification of bicuspid
      aortic valve before aortic valve surgery. METHODS: Of 1203 patients who underwent
      an aortic valve operation, 218 had both preoperative transthoracic
      echocardiography and cardiac magnetic resonance imaging. Patients in the study
      group were aged 56 years and had an ejection fraction of 56%, 76% were male, and
      29% had associated coronary artery disease. The results of transthoracic
      echocardiography and cardiac magnetic resonance imaging were classified as
      bicuspid aortic valve, trileaflet aortic valve, or nondiagnostic. Of the 218
      patients, 123 (56%) had bicuspid aortic valve as determined at the time of
      surgery and 116 (53%) had an ascending aortic aneurysm. RESULTS: Of the 123
      patients with bicuspid aortic valve confirmed at surgery, by transthoracic
      echocardiography 76 (62%) were identified preoperatively with bicuspid aortic
      valve, 12 (10%) were misidentified with trileaflet aortic valve, and 35 (28%)
      were nondiagnostic for valve morphology. In the same patients with bicuspid
      aortic valve, by cardiac magnetic resonance imaging 115 (93%) were identified
      with bicuspid aortic valve, 5 (4%) were misidentified with trileaflet aortic
      valve, and 3 (2%) were nondiagnostic. The difference between transthoracic
      echocardiography and cardiac magnetic resonance imaging to determine the presence
      of bicuspid aortic valve was statistically significant (P<.001). In the entire
      cohort of patients, transthoracic echocardiography was diagnostic for valve
      morphology in 155 patients (71%) compared with cardiac magnetic resonance
      imaging, which was diagnostic in 212 patients (97%) (P<.001). CONCLUSIONS:
      Cardiac magnetic resonance imaging is more diagnostic than transthoracic
      echocardiography in determining the presence of bicuspid aortic valve. A
      significant factor is the rate of nondiagnostic transthoracic echocardiography
      for aortic valve morphology. Cardiac magnetic resonance imaging can be performed
      as a complementary test when transthoracic echocardiography is nondiagnostic for
      aortic valve morphology.

PMID- 22154794
TI  - Anomalous coronary arteries: depiction at dual-source computed tomographic
      coronary angiography.
AB  - OBJECTIVE: To retrospectively determine the imaging features of coronary artery
      anomalies depicted at dual-source computed tomographic coronary angiography (DSCT
      CA). METHODS: We reviewed the case histories of 12,145 patients with suspected
      coronary arterial disease who underwent DSCT-CA at our institution. Multiplanar
      reformation, maximum-intensity projection, and volume-rendered imaging were
      performed on an offline workstation. Each study was assessed retrospectively for
      the origin and course of the anomalous coronary artery by a minimum of 2
      cardiovascular radiologists; decisions were made in consensus. RESULTS: There
      were 124 (1.02%) patients with coronary anomalies. Fifty-one patients
      demonstrated an anomalous origin of the right coronary artery from the left sinus
      of Valsalva or the left main artery. An anomalous origin of a left circumflex
      artery from the right sinus of Valsalva or the right coronary artery was depicted
      in 17 patients. An anomalous origin of a left main artery from the right sinus of
      Valsalva was depicted in 1 patient. A single coronary artery was shown in 4
      patients, and congenital transposition of the great arteries was associated with
      this anomaly in 1 patient. In the remaining 50 patients, coronary artery fistulas
      were identified. Eight patients were referred after an equivocal conventional
      coronary angiogram. CONCLUSIONS: DSCT-CA is a reliable noninvasive tool that
      allows accurate delineation of coronary arterial anomalies in an appropriate
      clinical setting and provides detailed 3-dimensional anatomic information that
      may be difficult to obtain with invasive coronary angiography.

PMID- 22154796
TI  - Power loss and right ventricular efficiency in patients after tetralogy of Fallot
      repair with pulmonary insufficiency: clinical implications.
AB  - OBJECTIVES: To quantify right ventricular output power and efficiency and
      correlate these to ventricular function in patients with repaired tetralogy of
      Fallot. This might aid in determining the optimal timing for pulmonary valve
      replacement. METHODS: We reviewed the cardiac catheterization and magnetic
      resonance imaging data of 13 patients with tetralogy of Fallot (age, 22 +/- 17
      years). Using pressure and flow measurements in the main pulmonary artery,
      cardiac output and regurgitation fraction, right ventricular (RV) power output,
      loss, and efficiency were calculated. The RV function was evaluated using cardiac
      magnetic resonance imaging. RESULTS: The RV systolic power was 1.08 +/- 0.62 W,
      with 20.3% +/- 8.6% power loss owing to 41% +/- 14% pulmonary regurgitation
      (efficiency, 79.7% +/- 8.6%; 0.84 +/- 0.73 W), resulting in a net cardiac output
      of 4.24 +/- 1.82 L/min. Power loss correlated significantly with the indexed RV
      end-diastolic and end-systolic volume (R = 0.78, P = .002 and R = 0.69, P = .009,
      respectively). The normalized RV power output had a significant negative
      correlation with RV end-diastolic and end-systolic volumes (both R = -0.87, P =
      .002 and R = -0.68, P = .023, respectively). A rapid decrease occurred in the RV
      power capacity with an increasing RV volume, with the curve flattening out at an
      indexed RV end-diastolic and end-systolic volume threshold of 139 mL/m(2) and 75
      mL/m(2), respectively. CONCLUSIONS: Significant power loss is present in patients
      with repaired tetralogy of Fallot and pulmonary regurgitation. A rapid decrease
      in efficiency occurs with increasing RV volume, suggesting that pulmonary valve
      replacement should be done before the critical value of 139 mL/m(2) and 75
      mL/m(2) for the RV end-diastolic and end-systolic volume, respectively, to
      preserve RV function.

PMID- 22154797
TI  - Expanding the indications for septal myectomy in patients with hypertrophic
      cardiomyopathy: results of operation in patients with latent obstruction.
AB  - OBJECTIVE: Many patients with symptomatic hypertrophic cardiomyopathy have
      minimal left ventricular outflow tract gradients, and there is uncertainty
      whether their limitation is due to diastolic dysfunction or labile outflow tract
      obstruction. The purpose of this study was to characterize the clinical
      presentation and outcome of septal myectomy in patients with hypertrophic
      cardiomyopathy and latent obstruction. METHODS: Among 749 patients who underwent
      septal myectomy, 249 had latent obstruction with minimal (0-30 mm Hg) resting
      gradients preoperatively. All were symptomatic and had more severe left
      ventricular outflow tract obstruction provoked by Valsalva maneuver or amyl
      nitrite inhalation during Doppler echocardiography or by stimulation with
      isoproterenol during catheterization. Clinical characteristics, survival, and
      functional outcome of these patients were compared with those of 500 patients
      with more severe resting left ventricular outflow tract obstruction who underwent
      myectomy during the same period. RESULTS: Compared with those with severe
      obstruction, more patients with latent obstruction were male (63% vs 52%, P <
      .003), but ages were similar (53 +/- 14 years vs 52 +/- 15 years). Preoperative
      symptoms and functional limitation were similar in the 2 groups with 86% and 85%,
      respectively, having New York Heart Association class III or IV disability. Among
      patients with latent obstruction, mixed venous oxygen saturation was 61.6% +/-
      19.0% of predicted compared with 56.8% +/- 17.3% for those with severe resting
      obstruction (P < .008). Septal thickness was less in patients with latent
      obstruction (20 +/- 9 mm vs 22 +/- 15 mm, P < .001). Early mortality was 1% in
      each group, and survival at 5 and 10 years was 93% and 87%, respectively, for
      patients with latent obstruction compared with 93% and 74%, respectively, for
      patients with severe resting obstruction preoperatively (P = .34). Self-reported
      late functional status was similar; 3 to 5 years postoperatively, 81% of patients
      with latent obstruction preoperatively were in New York Heart Association class I
      or II compared with 77% of patients with severe resting obstruction. CONCLUSIONS:
      Patients with obstructive hypertrophic cardiomyopathy who have low resting
      gradients and latent obstruction may have limiting symptoms comparable to those
      of patients with more severe resting gradients. Septal myectomy should be offered
      to these patients because survival and symptom relief are excellent, suggesting
      that dynamic obstruction is the major hemodynamic problem rather than diastolic
      dysfunction.

PMID- 22154799
TI  - Expression profiling of more than 3500 proteins of MSS-type colorectal cancer by
      stable isotope labeling and mass spectrometry.
AB  - An efficient means of identifying protein biomarkers is essential to proper
      cancer management. A well-characterized proteome resource holds special promise
      for the discovery of novel biomarkers. However, quantification of the differences
      between physiological conditions together with deep down profiling has become
      increasingly challenging in proteomics. Here, we perform expression profiling of
      the colorectal cancer (CRC) proteome by stable isotope labeling and mass
      spectrometry. Quantitative analysis included performing mTRAQ and cICAT labeling
      in a pooled sample of three microsatellite stable (MSS) type CRC tissues and a
      pooled sample of their matched normal tissues. We identified and quantified a
      total of 3688 proteins. Among them, 1487 proteins were expressed differentially
      between normal and cancer tissues by higher than 2-fold; 1009 proteins showed
      increased expression in cancer tissue, whereas 478 proteins showed decreased
      expression. Bioinformatic analysis revealed that our data were largely consistent
      with known CRC relevant signaling pathways, such as the Wnt/beta-catenin,
      caveolar-mediated endocytosis, and RAN signaling pathways. Mitochondrial
      dysfunction, known as the Waburg hypothesis, was also confirmed. Therefore, our
      data showing alterations in the proteomic profile of CRC constitutes a useful
      resource that may provide insights into tumor progression with later goal of
      identifying biologically and clinically relevant marker proteins. This article is
      part of a Special Issue entitled: Proteomics: The clinical link.

PMID- 22154798
TI  - On-pump versus off-pump coronary artery bypass surgery in high-risk patients:
      operative results of a prospective randomized trial (on-off study).
AB  - OBJECTIVE: To analyze the risk reduction of cardiopulmonary bypass complications
      between on-pump and off-pump coronary artery bypass grafting in high-risk
      patients. METHODS: This multicenter, prospective, randomized, parallel trial
      enrolled patients for elective or urgent isolated coronary artery bypass grafting
      with an additive European System for Cardiac Operative Risk Evaluation of 6 or
      more. The patients in cardiogenic shock were excluded. The composite primary end
      point included operative mortality, myocardial infarction, stroke, renal failure,
      reoperation for bleeding and adult respiratory distress syndrome within 30 days
      after surgery. The total sample size was 693 patients, according to a scheduled
      interim analysis at 400 patients enrolled (alpha-spending = 0.029, Pocock
      method). RESULTS: A total of 411 patients were included in the interim analysis.
      Randomization assigned 203 patients to on-pump and 208 patients to off-pump
      treatment. Of the 411 patients, 24 crossed over; thus, 195 patients were actually
      treated on-pump and 216 off-pump. According to the intention to treat analysis,
      the rate of the composite primary end point was significantly lower (unadjusted P
      = .009, adjusted P = .010) in the off-pump group (5.8% vs 13.3%). The risk of
      experiencing the primary end point was significantly greater for the on-pump
      group (unadjusted odds ratio, 2.51; 95% confidence interval, 1.23-5.10; P = .011;
      adjusted odds ratio, 3.07; 95% confidence interval, 1.32-7.14; P = .009).
      CONCLUSIONS: Off-pump coronary artery bypass grafting reduces early mortality and
      morbidity in high-risk patients.

PMID- 22154800
TI  - The neurosteroids, allopregnanolone and progesterone, induce autophagy in
      cultured astrocytes.
AB  - Recent studies have suggested that neurosteroids such as pregnenolone,
      progesterone (PG) and their derivatives, have a role in activating autophagy in
      addition to diverse other functions. In our previous studies, we demonstrated
      that cellular free Zn(2+) is involved in oxidative stress-induced autophagy and
      autophagic cell death in astrocytes. In the present study, we examined the
      possibility that neurosteroids, allopregnanolone (Allo) and PG, also activate
      autophagy in cultured mouse astrocytes through modulation of intracellular
      Zn(2+). Exposure of astrocytes to 250 nM Allo or 500 nM PG caused cytosolic
      vacuoles to appear within a few hours of treatment onset. Live-cell confocal
      microscopy of astrocytes transfected with red fluorescent protein-conjugated LC3
      (RFP-LC3), a marker for autophagic vacuoles (AVs), as well as transmission
      electron microscopy, revealed that these vacuoles were AVs. In addition, Western
      blots showed increases in LC3-II levels. Interestingly, mTOR and Akt were
      concurrently activated, and their blockade further increased LC3-II levels and
      caused some cell death. These results indicate that co-activation of mTOR and Akt
      may act to limit neurosteroid-induced autophagy and thus inhibit autophagic cell
      death. As in other cases of autophagy, cellular Zn(2+) levels increased after
      treatment with neurosteroids. The neurosteroid-induced increase in LC3-II levels
      was inhibited by addition of the Zn(2+) chelator TPEN. Both the increase in LC3
      II levels and activation of Akt and mTOR by neurosteroids were all mediated by PG
      receptors, as the effects were blocked by the addition of RU-486, a PG receptor
      antagonist. Moreover, mutant huntingtin (mHtt) aggregates in GFP-mHttQ74
      transfected astrocytes were substantially reduced by neurosteroid treatment,
      indicating that neurosteroid-induced autophagy may be functional. Present results
      demonstrate that Allo and PG activate autophagy in astrocytes. Notably, unlike
      several other autophagy inducers that, in excess, may cause autophagic cell
      death, Allo and PG are relatively non-toxic, possibly because of concurrent Akt
      and mTOR activation. Thus, as natural endogenous brain substances, Allo and PG
      may have a potential as therapeutic agents in neurodegenerative conditions in
      which abnormal protein aggregates are involved.

PMID- 22154801
TI  - Therapeutic benefits of the group B3 vitamin nicotinamide in mice with lethal
      endotoxemia and polymicrobial sepsis.
AB  - Nicotinamide (NAM) is a group B3 vitamin involved in a wide range of biological
      processes. Recently, the anti-inflammatory properties of NAM have been revealed.
      In this study, we investigated the therapeutic effects of NAM in murine models of
      endotoxemia and sepsis. Endotoxemic liver injury was induced by intraperitoneal
      injection of lipopolysaccharide (LPS) into D-galactosamine (D-Gal)-sensitized
      mice. Lethal endotoxemia was induced by intraperitoneal administration of LPS at
      a dose of 20 mg/kg. Polymicrobial sepsis was induced by cecal ligation and
      puncture (CLP). In mice challenged with LPS/D-Gal, treatment with NAM
      significantly deceased serum aminotransferases level and alleviated hepatic
      lesions. NAM also reduced serum tumor necrosis factor-alpha level and attenuated
      apoptosis in liver, as assessed by terminal deoxynucleotidyl transferase-mediated
      nucleotide nick end labeling (TUNEL) staining and measurements of caspases
      activities. Survival analysis indicated that NAM reduced the mortality rate of
      LPS/D-Gal-challenged mice. In mice with lethal endotoxemia, NAM reduced serum
      level of pro-inflammatory cytokines and multiple organ damage as evidence by
      improved morphological lesion, reduced lung wet to dry ratio as well as decreased
      serum level of aminotransferase and blood urea nitrogen. In survival analysis,
      treatment with NAM increased the survival rate of mice with lethal endotoxemia or
      CLP-induced polymicrobial sepsis. Taken together, treatment with NAM might
      provide therapeutic benefits in sepsis, which attenuated inflammatory injury and
      improved the survival rate.

PMID- 22154802
TI  - Metabolic syndrome potentiates the cardiac action potential-prolonging action of
      drugs: a possible 'anti-proarrhythmic' role for amlodipine.
AB  - Type II diabetes was shown to prolong the QT interval on the ECG and to promote
      cardiac arrhythmias. This is not so clear for metabolic syndrome, a precursor
      state of type II diabetes. The objectives of the present study were to generate a
      guinea pig model of metabolic syndrome by long-term exposure to diabetogenic
      diets, and to evaluate the monophasic action potential duration (MAPD)-modulating
      effects of drugs in these animals. Male Hartley guinea pigs were fed with either
      the control, the High Fat High Sucrose (HFHS) or the High Fat High Fructose
      (HFHF) diet for 150 days. Evolution of weight, blood cholesterol, triglycerides,
      urea and glucose tolerance were regularly monitored. Histopathological evolution
      was also evaluated in target organs such as pancreas, heart, liver and kidneys.
      Ex vivo experiments using the Langendorff retroperfusion technique, isolated
      hearts from guinea pigs either fed with the control, the HFHS or the HFHF diet
      were exposed to dofetilide 20 nM (D), chromanol 293B 10 MUM (C) and amlodipine
      100 nM (A) in different drug combinations and monophasic action potential
      duration was measured at 90% repolarization (MAPD90). Our data show that it is
      possible to generate a guinea pig model of metabolic syndrome by chronic exposure
      to diabetogenic diets. Minor histopathological abnormalities were observed,
      mainly in the pancreas and the liver. Metabolic syndrome potentiates the MAPD
      prolonging actions of I(Kr)-blocking (dofetilide) and I(Ks)-blocking (chromanol
      293B) drugs, an effect that is reversible upon administration of the calcium
      channel blocker amlodipine.

PMID- 22154803
TI  - Structural characterization of the RNA chaperone Hfq from the nitrogen-fixing
      bacterium Herbaspirillum seropedicae SmR1.
AB  - The RNA chaperone Hfq is a homohexamer protein identified as an E. coli host
      factor involved in phage Qbeta replication and it is an important
      posttranscriptional regulator of several types of RNA, affecting a plethora of
      bacterial functions. Although twenty Hfq crystal structures have already been
      reported in the Protein Data Bank (PDB), new insights into these protein
      structures can still be discussed. In this work, the structure of Hfq from the
      beta-proteobacterium Herbaspirillum seropedicae, a diazotroph associated with
      economically important agricultural crops, was determined by X-ray
      crystallography and small-angle X-ray scattering (SAXS). Biochemical assays such
      as exclusion chromatography and RNA-binding by the electrophoretic shift assay
      (EMSA) confirmed that the purified protein is homogeneous and active. The crystal
      structure revealed a conserved Sm topology, composed of one N-terminal alpha
      helix followed by five twisted beta-strands, and a novel pi-pi stacking intra
      subunit interaction of two histidine residues, absent in other Hfq proteins.
      Moreover, the calculated ab initio envelope based on small-angle X-ray scattering
      (SAXS) data agreed with the Hfq crystal structure, suggesting that the protein
      has the same folding structure in solution.

PMID- 22154804
TI  - Sex differences on the judgment of line orientation task: a function of landmark
      presence and hormonal status.
AB  - It has been well-established that men outperform women on some spatial tasks. The
      tools commonly used to demonstrate this difference (e.g. The Mental Rotations
      Task) typically involve problems and solutions that are presented in a context
      devoid of referents. The study presented here assessed whether the addition of
      referents (or "landmarks") would attenuate the well-established sex difference on
      the judgment of line orientation task (JLOT). Three versions of the JLOT were
      presented in a within design. The first iteration contained the original JLOT
      (JLOT 1). JLOT 2 contained three "landmarks" or referents and JLOT 3 contained
      only one landmark. The sex difference on JLOT 1 was completely negated by the
      addition of three landmarks on JLOT 2 or the addition of one landmark on JLOT3.
      In addition, salivary testosterone was measured. In men, gains in performance on
      the JLOT due to the addition of landmarks were positively correlated with
      testosterone levels. This suggests that men with the highest testosterone levels
      benefited the most from the addition of landmarks. These data help to highlight
      different strategies used by men and women to solve spatial tasks.

PMID- 22154805
TI  - Motor and cognitive deficits in mice bred to have low or high blood pressure.
AB  - Deviations from normal blood pressure can lead to a number of physiological and
      behavioral complications. We tested the hypothesis that hyper- or hypotension is
      associated with significant differences in motor activity and coordination,
      anxiety levels, and spatial learning and memory in male and female mice. Compared
      to normotensive control mice, hypertensive mice were hyperactive and their
      performance was significantly worse on the rotarod (males only), cued learning
      (males only), spatial learning/re-learning, and spatial memory. Hypotensive mice
      of both genders swam more slowly and performed even worse than hypertensive mice
      on the rotarod, cued learning, spatial learning/re-learning, and spatial memory
      tasks. Across all phenotypes, females were generally more active than males in
      the open field and exhibited more anxiety-like behaviors in the elevated zero
      maze. Alterations in hemodynamics and/or neurovascular unit function may account
      for the observed behavioral changes in the hypo- and hypertensive mice.

PMID- 22154806
TI  - CECR2 is involved in spermatogenesis and forms a complex with SNF2H in the
      testis.
AB  - The regulation of nucleosome positioning and composition by ATP-dependent
      chromatin remodeling enzymes and their associated binding partners plays
      important biological roles in mammals. CECR2 is a binding partner to the ISWI
      (imitation switch) ATPase SNF2L/SMARCA1 and is involved in neural tube closure
      and inner ear development; however, its functions in adult tissues have not been
      examined. Here, we report that CECR2 contributes to spermatogenesis and forms a
      complex that includes the other ISWI ATPase SNF2H/SMARCA5 in the testis. Cecr2
      mutant males non-penetrant for neural tube defects sired smaller litters than
      wild-type males. Strikingly, while we found that Cecr2 mutants have normal
      seminiferous epithelium morphology, sperm count, motility, and morphology, the
      mutant spermatozoa were compromised in their ability to fertilize oocytes.
      Investigation of CECR2/ISWI complexes in the testis showed that SNF2H interacted
      with CECR2, and this interaction was also observed in embryonic stem cells,
      suggesting that CECR2 may interact with SNF2H or SNF2L depending on the cell
      type. Finally, we found that Cecr2 mutants exhibit misregulation of the homeobox
      transcription factor Dlx5 in the testis, suggesting that CECR2 complexes may
      regulate gene expression during spermatogenesis. Taken together, our results
      demonstrate a novel role of CECR2-containing complexes in spermatogenesis and
      show that CECR2 interacts predominantly with SNF2H instead of SNF2L in the
      testis.

PMID- 22154807
TI  - Dynamic cross-talk among remote binding sites: the molecular basis for unusual
      synergistic allostery.
AB  - Allosteric regulation of protein function is critical for metabolic control.
      Binding of allosteric effectors elicits a functional change in a remote ligand
      binding site on a protein by altering the equilibrium between different forms in
      the protein ensemble. 3-Deoxy-d-arabino-heptulosonate 7-phosphate synthase
      (DAH7PS) catalyzes the first step in the shikimate pathway, which is responsible
      for the biosynthesis of aromatic amino acids Trp, Phe, and Tyr. Feedback
      regulation by the aromatic amino acids is important for controlling the cellular
      levels of the aromatic amino acids, and many organisms have two or more DAH7PS
      isozymes that show differing sensitivities to aromatic compounds. Mycobacterium
      tuberculosis expresses a single DAH7PS that is insensitive to the presence of a
      single amino acid yet shows extraordinary synergistic inhibition by combinations
      of the pathway end products Trp and Phe. The Trp+Phe-bound structure for M.
      tuberculosis DAH7PS, showing two separate binding sites occupied by Trp and Phe
      for each monomer of the tetrameric protein, was obtained by cocrystallization.
      Comparison of this structure with the ligand-free M. tuberculosis DAH7PS
      demonstrates that there is no significant change in conformation upon ligand
      binding, suggesting that contributions from altered dynamic properties of the
      enzyme may account for the allosteric inhibition. Isothermal titration
      calorimetry experiments demonstrate that the inhibitor binding sites are in
      direct communication. Molecular dynamics simulations reveal different changes in
      dynamic fluctuations upon single ligand binding compared to dual ligand binding.
      These changes account for the cross-talk between inhibitor binding sites and the
      active site, simultaneously potentiating both dual ligand binding and diminution
      of catalytic function.

PMID- 22154808
TI  - Three RNA recognition motifs participate in RNA recognition and structural
      organization by the pro-apoptotic factor TIA-1.
AB  - T-cell intracellular antigen-1 (TIA-1) regulates developmental and stress
      responsive pathways through distinct activities at the levels of alternative pre
      mRNA splicing and mRNA translation. The TIA-1 polypeptide contains three RNA
      recognition motifs (RRMs). The central RRM2 and C-terminal RRM3 associate with
      cellular mRNAs. The N-terminal RRM1 enhances interactions of a C-terminal Q-rich
      domain of TIA-1 with the U1-C splicing factor, despite linear separation of the
      domains in the TIA-1 sequence. Given the expanded functional repertoire of the
      RRM family, it was unknown whether TIA-1 RRM1 contributes to RNA binding as well
      as documented protein interactions. To address this question, we used isothermal
      titration calorimetry and small-angle X-ray scattering to dissect the roles of
      the TIA-1 RRMs in RNA recognition. Notably, the fas RNA exhibited two binding
      sites with indistinguishable affinities for TIA-1. Analyses of TIA-1 variants
      established that RRM1 was dispensable for binding AU-rich fas sites, yet all
      three RRMs were required to bind a polyU RNA with high affinity. Small-angle X
      ray scattering analyses demonstrated a "V" shape for a TIA-1 construct comprising
      the three RRMs and revealed that its dimensions became more compact in the RNA
      bound state. The sequence-selective involvement of TIA-1 RRM1 in RNA recognition
      suggests a possible role for RNA sequences in regulating the distinct functions
      of TIA-1. Further implications for U1-C recruitment by the adjacent TIA-1 binding
      sites of the fas pre-mRNA and the bent TIA-1 shape, which organizes the N- and C
      termini on the same side of the protein, are discussed.

PMID- 22154809
TI  - Solution structure of the HIV-1 exon splicing silencer 3.
AB  - Alternative splicing of the human immunodeficiency virus type 1 (HIV-1) genomic
      RNA is necessary to produce the complete viral protein complement, and
      aberrations in the splicing pattern impair HIV-1 replication. Genome splicing in
      HIV-1 is tightly regulated by the dynamic assembly/disassembly of trans host
      factors with cis RNA control elements. The host protein, heterogeneous nuclear
      ribonucleoprotein (hnRNP) A1, regulates splicing at several highly conserved HIV
      1 3' splice sites by binding 5'-UAG-3' elements embedded within regions
      containing RNA structure. The physical determinants of hnRNP A1 splice site
      recognition remain poorly defined in HIV-1, thus precluding a detailed
      understanding of the molecular basis of the splicing pattern. Here, the three
      dimensional structure of the exon splicing silencer 3 (ESS3) from HIV-1 has been
      determined using NMR spectroscopy. ESS3 adopts a 27-nucleotide hairpin with a 10
      bp A-form stem that contains a pH-sensitive A(+)C wobble pair. The seven
      nucleotide hairpin loop contains the high-affinity hnRNP-A1-responsive 5'-UAGU-3'
      element and a proximal 5'-GAU-3' motif. The NMR structure shows that the
      heptaloop adopts a well-organized conformation stabilized primarily by base
      stacking interactions reminiscent of a U-turn. The apex of the loop is quasi
      symmetric with UA dinucleotide steps from the 5'-GAU-3' and 5'-UAGU-3' motifs
      stacking on opposite sides of the hairpin. As a step towards understanding the
      binding mechanism, we performed calorimetric and NMR titrations of several hnRNP
      A1 subdomains into ESS3. The data show that the UP1 domain forms a high-affinity
      (K(d)=37.8+/-1.1 nM) complex with ESS3 via site-specific interactions with the
      loop.

PMID- 22154810
TI  - Action of ANP on the nongenomic dose-dependent biphasic effect of aldosterone on
      NHE1 in proximal S3 segment.
AB  - The rapid (2 min) nongenomic effects of aldosterone (ALDO) and/or spironolactone
      (MR antagonist), RU 486 (GR antagonist), atrial natriuretic peptide (ANP) and
      dimethyl-BAPTA (BAPTA) on the intracellular pH recovery rate (pHirr) via NHE1
      (basolateral Na+/H+ exchanger isoform), after the acid load induced by NH4Cl, and
      on the cytosolic free calcium concentration ([Ca2+](i)) were investigated in the
      proximal S3 segment isolated from rats, by the probes BCECF-AM and FLUO-4-AM,
      respectively. The basal pHi was 7.15+/-0.008 and the basal pHirr was 0.195+/
      0.012 pH units/min (number of tubules/number of tubular areas=16/96). Our results
      confirmed the rapid biphasic effect of ALDO on NHE1: ALDO (10-12 M) increases the
      pHirr to approximately 59% of control value, and ALDO (10-6 M) decreases it to
      approximately 49%. Spironolactone did not change these effects, but RU 486
      inhibited the stimulatory effect and maintained the inhibitory effect. ANP (10-6
      M) or BAPTA (5*10-5 M) alone had no significant effect on NHE1 but prevented both
      effects of ALDO on this exchanger. The basal [Ca2+](i) was 104+/-3 nM (15), and
      ALDO (10-12 or 10-6 M) increased the basal [Ca2+](i) to approximately 50% or
      124%, respectively. RU 486, ANP and BAPTA decreased the [Ca2+](i) and inhibited
      the stimulatory effect of both doses of ALDO. The results suggest the involvement
      of GR on the nongenomic effects of ALDO and indicate a pHirr-regulating role for
      [Ca2+](i) that is mediated by NHE1, stimulated/impaired by ALDO, and affected by
      ANP or BAPTA with ALDO. The observed nongenomic hormonal interaction in the S3
      segment may represent a rapid and physiologically relevant regulatory mechanism
      in the intact animal under conditions of volume alterations.

PMID- 22154811
TI  - Sweeping as trick for chronic motor tics.

PMID- 22154812
TI  - Bioelectrochemistry of non-covalent immobilized alcohol dehydrogenase on oxidized
      diamond nanoparticles.
AB  - Diamond nanoparticles are considered a biocompatible material mainly due to their
      non-cytotoxicity and remarkable cellular uptake. Model proteins such as
      cytochrome c and lysozyme have been physically adsorbed onto diamond
      nanoparticles, proving it to be a suitable surface for high protein loading.
      Herein, we explore the non-covalent immobilization of the redox enzyme alcohol
      dehydrogenase (ADH) from Saccharomyces cerevisiae (E.C.1.1.1.1) onto oxidized
      diamond nanoparticles for bioelectrochemical applications. Diamond nanoparticles
      were first oxidized and physically characterized by X-ray diffraction (XRD), FT
      IR and TEM. Langmuir isotherms were constructed to investigate the ADH adsorption
      onto the diamond nanoparticles as a function of pH. It was found that a higher
      packing density is achieved at the isoelectric point of the enzyme. Moreover, the
      relative activity of the immobilized enzyme on diamond nanoparticles was
      addressed under optimum pH conditions able to retain up to 70% of its initial
      activity. Thereafter, an ethanol bioelectrochemical cell was constructed by
      employing the immobilized alcohol dehydrogenase onto diamond nanoparticles, this
      being able to provide a current increment of 72% when compared to the blank
      solution. The results of this investigation suggest that this technology may be
      useful for the construction of alcohol biosensors or biofuel cells in the near
      future.

PMID- 22154813
TI  - A brief assessment tool for body image in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) may adversely affect body image in multitude
      ways. Development and validation of a brief and valid SLE specific body image
      tool were undertaken. Eleven items were identified on interview of 21 SLE
      patients for the Body Image Lupus Scale (BILS v1.0). The tool was administered to
      70 SLE patients. Based on analysis, feedback, and refinement of items, the final
      iteration BILS v1.2 with five items was administered to 233 SLE patients along
      with validated body image measures (Situational Inventory of Body Image Dysphoria
      and Body Image Quality of Life Inventory) and health-related quality of life
      measures for a subsample. The BILS scores' had an internal consistency
      reliability of .94. It correlated with both the referent body image measures, and
      with health-related quality of life. It differentiated participants by health
      status and disease activity. Test-retest reliability estimates exceeded .90.
      These results support the psychometric properties of BILS.

PMID- 22154815
TI  - Novel tri-peptides with hypopigmenting activity.

PMID- 22154814
TI  - Nucleobindins: bioactive precursor proteins encoding putative endocrine factors?
AB  - The nucleobindins, nucleobindin 1 (NUCB1) and nucleobindin 2 (NUCB2), are
      homologous multidomain calcium and DNA binding proteins. NUCB1 is a well
      characterized Golgi protein found within the rat pituitary, liver and kidney with
      functions related to immunity, calcium homeostasis and G protein signaling. NUCB2
      is found both in the hypothalamus and brain stem centers, as well as peripherally
      in the digestive tract. Renewed interest in the nucleobindins has been sparked by
      the recent discovery of nesfatin-1, an endocrine factor post-translationally
      processed from the N-terminal of NUCB2. Nesfatin-1 has quickly established itself
      as a novel regulator of appetite, insulin secretion, energy homeostasis and
      reproduction with important consequences to the etiology of metabolic diseases
      including diabetes and obesity. The discovery of nesfatin-1 and it endocrine
      functions attracted more attention to the nucleobindins that are already known to
      have important intracellular functions. From the sequence information available,
      it is possible that nucelobindins itself or nesfatin-1 like peptides within the
      NUCB1 could also elicit nesfatin-1-like biological functions. The research on
      nesfatin-1 in last 5years further adds to the importance of nucleobindins as
      potential endocrine precursors. This review aims to summarize some of the most
      recent findings on the functional significance of NUCB1, NUCB2, as well as
      encoded proteins and highlights the questions that remain unanswered.

PMID- 22154816
TI  - The role of TRPV1 channel in aged human skin.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is a member of the nonselective
      cationic channel family. Activation of TRPV1 induces an influx of divalent and
      monovalent cations (i.e., Ca(2+), Na(+), and Mg(2+)) which are activated by
      capsaicin, heat, and acid. TRPV1 is known to be expressed in the epidermis, but
      little is known about the physiological significance and functional role of TRPV1
      in skin. Recent studies suggested that heat- and ultraviolet (UV)-induced matrix
      metalloproteinases-1 (MMP-1) expression may be partly mediated by TRPV1
      activation in human keratinocytes. Also, heat and UV increased expression of
      TRPV1 proteins in human skin in vivo. TRPV1 protein was expressed more in the sun
      protected (upper-inner arm) skin of the elderly than in young subjects. In
      addition, the photoaged (forearm) skin of the elderly showed increased TRPV1
      expression compared to sun-protected skin of the same individuals. The increased
      TRPV1 expression in the old skin implies that TRPV1 may be related to senile skin
      symptoms, such as senile pruritus and neurogenic inflammation. This review
      provides a summary of current researches on the role of TRPV1 channel in human
      skin, especially in aged skin.

PMID- 22154818
TI  - Protein kinase Cdelta negatively regulates Notch1-dependent transcription via a
      kinase-independent mechanism in vitro.
AB  - Protein kinase Cdelta (PKCdelta) plays a significant role in the regulation of
      growth, apoptosis, and differentiation in a diversity of cell types. We
      investigated the effect of PKCdelta on Notch1 intracellular domain (NICD)
      mediated transcription with Notch transcription reporter constructs. The results
      indicate that co-expression of PKCdelta down-regulated NICD-dependent
      transcription. Co-expression of a dominant negative PKCdelta (K376R) variant
      lacking kinase activity was also able to downregulate NICD-dependent
      transcription, suggesting that PKCdelta exerts its inhibitory effect via a kinase
      independent mechanism(s). Interestingly, expression of PKCdelta as well as K376R
      induced NICD up-regulation by inhibiting proteasome-mediated degradation of NICD,
      indicating that NICD protein quantity is not proportional to its transcriptional
      activity. When the subcellular distribution of NICD was investigated by both
      subcellular fractionation and immunocytochemistry, it was found that PKCdelta and
      K376R effectively impaired proper nuclear localization of NICD, possibly via a
      physical association between NICD and PKCdelta, which was confirmed by co
      immunoprecipitation experiments. Chromatin immunoprecipitation assays revealed
      that both PKCdelta and K376R inhibit the association of NICD with the promoter
      region of its target gene, Hes1. Furthermore, silencing of PKCdelta resulted in
      increased NICD nuclear localization and NICD transcriptional activity in MCF-7
      cells. PKCdelta silencing-induced increase in anti-apoptotic survivin could not
      rescue apoptosis induced by doxorubicin. The data herein indicate that PKCdelta
      can induce down-regulation of NICD transcriptional activity via a kinase
      independent inhibition of NICD nuclear targeting and dissociation of NICD from
      target gene promoters.

PMID- 22154817
TI  - Broad action of Hsp90 as a host chaperone required for viral replication.
AB  - Viruses are intracellular pathogens responsible for a vast number of human
      diseases. Due to their small genome size, viruses rely primarily on the
      biosynthetic apparatus of the host for their replication. Recent work has shown
      that the molecular chaperone Hsp90 is nearly universally required for viral
      protein homeostasis. As observed for many endogenous cellular proteins, numerous
      different viral proteins have been shown to require Hsp90 for their folding,
      assembly, and maturation. Importantly, the unique characteristics of viral
      replication cause viruses to be hypersensitive to Hsp90 inhibition, thus
      providing a novel therapeutic avenue for the development of broad-spectrum
      antiviral drugs. The major developments in this emerging field are hereby
      discussed. This article is part of a Special Issue entitled: Heat Shock Protein
      90 (HSP90).

PMID- 22154820
TI  - Chronic circadian disturbance by a shortened light-dark cycle increases
      mortality.
AB  - Chronic circadian disturbance, a condition of desynchronization between
      endogenous clock and environmental light-dark (LD) cycle, is known to cause
      adverse physiological changes including mortality. However, it is yet unclear
      whether these consequences result from disturbance of endogenous clock or
      condition of the LD cycle per se. To address this issue, we imposed 3 different
      periods of LD cycle (T) on wild type and functional clock-defective (Per1(-/
      )Per2(-/-)) mice. We found that the disturbed rhythms of locomotor activity and
      body temperature resulted from interaction of endogenous clock and T cycle and
      the chronic state of the disturbance suppressed the endogenous circadian rhythm.
      Interestingly, the endogenous clock and the T cycles affected body weight and
      food intake independently, while their interaction affected the life span
      resulting increased mortality of wild type mice in a shortened T cycle. These
      results strongly indicate the presence of both separate and combined effects of
      the endogenous clock and T cycle on different physiological variables implying
      that shift work scheduling can be an important influence on health parameters.

PMID- 22154819
TI  - Age-related severity of focal ischemia in female rats is associated with impaired
      astrocyte function.
AB  - In middle-aged female rats, focal ischemia leads to a larger cortical infarction
      as compared with younger females. To determine if stroke-induced cytotoxicity in
      middle-aged females was associated with impaired astrocyte function, astrocytes
      were harvested and cultured from the ischemic cortex of young and middle-aged
      female rats. Middle-aged astrocytes cleared significantly less glutamate from
      media as compared with young female astrocytes. Furthermore, astrocyte
      conditioned media from middle-aged female astrocytes induced greater migration of
      peripheral blood monocyte cells (PBMCs) and expressed higher levels of the
      chemoattractant macrophage inflammatory protein-1 (MIP-1). Middle-aged astrocytes
      also induced greater migration of neural progenitor cells (NPCs), however, their
      ability to promote neuronal differentiation of neural progenitor cells was
      similar to young astrocytes. In males, where cortical infarct volume is similar
      in young and middle-aged animals, no age-related impairment was observed in
      astrocyte function. These studies show that the aging astrocyte may directly
      contribute to infarct severity by inefficient glutamate clearance and enhanced
      cytokine production and suggest a cellular target for improved stroke therapy
      among older females.

PMID- 22154821
TI  - Exome sequencing reveals SPG11 mutations causing juvenile ALS.
AB  - We report here the description of a nonconsanguineous family with 2 affected
      individuals with a recessively inherited juvenile motor neuron disease. Exome
      sequencing of these 2 affected individuals led us to identify 2 compound
      heterozygous deletions leading to a frameshift and a premature stop codon in the
      SPG11 gene. One of these deletions, c.5199delA in exon 30, has not been
      previously reported. Interestingly, these deletions are associated with an
      intrafamilial phenotypic heterogeneity as one affected has atypical juvenile
      amyotrophic lateral sclerosis (ALS) and the other has classical hereditary
      spastic paraplegia with thin corpus callosum. Our findings confirm SPG11 as a
      genetic cause of juvenile amyotrophic lateral sclerosis and indicate that SPG11
      mutations could be associated with 2 different clinical phenotypes within the
      same family.

PMID- 22154822
TI  - Micellization of mixtures of amphiphilic drugs and cationic surfactants: a
      detailed study.
AB  - The micellization behaviors of two amphiphilic drugs ((amitriptyline
      hydrochloride (AMT) and imipramine hydrochloride (IMP)) in presence of cationic
      surfactants (conventional as well as gemini) have been investigated
      conductometrically at four mole fractions and four temperatures. The critical
      micelle concentration (cmc) values come out to be lower than cmc(id) values
      (cmc(id) is the cmc value at ideal mixing state) indicating attractive
      interactions between the two components in mixed micelles. Micellar mole
      fractions of surfactants (X(1) and X(1)(M)), calculated by Rubingh and Motomura
      models, are always greater than X(1)(id) (micellar mole fraction at ideal
      mixing). The rigid structure of drugs decreases their contribution in mixed
      micelles as compared to that predicted by X(1)(id) values. Although alpha(1)
      (mole fraction of surfactant) is higher for DTAB than that of 12-4-12, the
      contribution of 12-4-12 is almost equal to that of DTAB. The interaction
      parameter (beta) is negative at all temperatures and at all compositions
      indicating attractive interactions. Activity coefficients (f(1) and f(2)) are
      always less than unity suggesting nonideality in the systems. Thermodynamic
      parameters suggest dehydration of hydrophobic part of the drug at or above
      certain temperature which is different for the two drugs.

PMID- 22154823
TI  - Chronic ritodrine treatment induces refractoriness of glucose-lowering beta2
      adrenoceptor signal in female mice.
AB  - Adverse events in tocolytic therapy with beta2-adrenergic agents compromise
      cardiovascular and non-cardiovascular functions, including blood glucose
      regulation and liver function. Here, we have examined the effects of the beta2
      agonist ritodrine on glucose metabolism and liver injury in mice. Under fasting
      conditions, ritodrine significantly increased serum insulin levels and decreased
      glucose concentrations. This contrasts with the beta2 agonist-induced
      hyperglycemia observed in previous studies on humans and other animals. After 14
      days of ritodrine treatment, the mice showed a decrease in the total mass of
      epididymal fat pads, whereas their body weights increased significantly. Chronic
      ritodrine treatment attenuated the glucose-lowering effect observed during acute
      administration. Ritodrine also significantly increased serum levels of liver
      enzymes, which returned to control levels after 14 days of treatment. Thus,
      ritodrine responsiveness changes between acute and chronic treatment, indicating
      that close monitoring of blood glucose and serum liver enzymes is necessary in
      patients with reduced glucose tolerance. The findings reported here of glucose
      homeostasis in mice provide a unique opportunity to understand refractoriness of
      beta2-adrenoceptor signaling in response to beta2 agonists during the course of
      treatment.

PMID- 22154824
TI  - Chitosan induced hepato-nephrotoxicity in mice with special reference to gender
      effect in glycolytic enzymes activities.
AB  - Chitosan is an antilipidemic dietary supplement used as a diet aide. The present
      study investigated the effect of sex-toxicity relationship between male and
      female mice orally given two dose levels (150 and 300 mg/kg) for 35 days.
      Chitosan treatment caused significant elevation in transaminases (ALT, AST) and
      alkaline phosphatase (ALP) in liver and in serum urea and creatinine in dose
      dependent manner; no sex differences between-treated groups. Lipid profile
      parameters significantly decreased and significant increase in glycolytic enzymes
      activities in all treatment groups. Female mice treated with chitosan (300 mg/kg)
      had significant reduction in lipid profile parameters than the same dose of male
      group. Phosphofructokinase (PFK) and lactate dehydrogenase (LDH) activities
      significantly enhanced without sex differences, while glucose phosphate isomerase
      (GPI) and hexokinase (HK) significantly elevated in the higher dose of females
      than male. Histopathological study of liver and kidney tissues showed moderate to
      severe histopathological changes depend on the dose and gender difference. Image
      analysis resulted significant depletion in glycogen and protein contents
      especially in female more than male. These results indicated that female mice
      were more susceptible to the toxic effect of chitosan than males when
      administered with the higher dose for a long period.

PMID- 22154825
TI  - Toxicological evaluation of Gumiganghwaltang aqueous extract in Crl:CD (SD) rats:
      13 weeks oral gavage studies.
AB  - Gumiganghwaltang is a traditional oriental herbal medicine that has been commonly
      used to treat colds and inflammatory diseases. Aqueous extract of
      Gumiganghwaltang (GMGHT) was administrated daily by oral gavage to male and
      female rats for 13 weeks. A dose of 2000 mg/kg/day was selected as a maximum, and
      doses of 1000 and 500 mg/kg/day were determined as medium and low doses,
      respectively. No treatment-related clinical signs or mortality were observed in
      the treatment group. We observed no clear treatment-related effects with regard
      to body weight, food consumption, ophthalmology, hematology, or urinalysis data.
      The serum biochemistry values for sodium and chloride in the treated male and
      female groups (1000 mg/kg/day) were lower than in those treated with the vehicle
      control. However, these changes lacked dose dependence, and no abnormalities were
      found in corresponding pathological findings. Our results indicated that the no
      observed-adverse-effect-level (NOAEL) for GMGHT was determined to be a dietary
      dose of over 2000 mg/kg/day for both sexes under the present experimental
      conditions.

PMID- 22154826
TI  - The use of heavy nitrogen in quantitative proteomics experiments in plants.
AB  - In the growing field of plant systems biology, there is an undisputed need for
      methods allowing accurate quantitation of proteins and metabolites. As
      autotrophic organisms, plants can easily metabolize different nitrogen isotopes,
      resulting in proteins and metabolites with distinct molecular mass that can be
      separated on a mass spectrometer. In comparative quantitative experiments,
      treated and untreated samples are differentially labeled by nitrogen isotopes and
      jointly processed, thereby minimizing sample-to-sample variation. In recent
      years, heavy nitrogen labeling has become a widely used strategy in quantitative
      proteomics and novel approaches have been developed for metabolite
      identification. Here, we present an overview of currently used experimental
      strategies in heavy nitrogen labeling in plants and provide background on the
      history and function of this quantitation technique.

PMID- 22154827
TI  - Integrating information on substance use disorders into electronic health record
      systems.
AB  - For reasons of safety and effectiveness, many forces in health care, especially
      the Affordable Care Act of 2010, are pressing for improved identification and
      management of substance use disorders within mainstream health care. Thus,
      standard information about patient substance use will have to be collected and
      used by providers within electronic health record systems (EHRS). Although there
      are many important technical, legal, and patient confidentiality issues that must
      be dealt with to achieve integration, this article focuses upon efforts by the
      National Institute on Drug Abuse and other federal agencies to develop a common
      set of core questions to screen, diagnose, and initiate treatment for substance
      use disorders as part of national EHRS. This article discusses the background and
      rationale for these efforts and presents the work to date to identify the
      questions and to promote information sharing among health care providers.

PMID- 22154828
TI  - Introduction to the special issue on organizational dynamics within substance
      abuse treatment: a complex human activity system.
AB  - Substance abuse treatment programs represent complex human activity systems in
      which multiple actors, including clients, counselors, and managers, are nested.
      Furthermore, treatment programs are nested within the broader environmental
      context of resource allocation and regulatory enforcement. This special issue of
      the Journal of Substance Abuse Treatment presents 12 empirical papers that
      address organizational dynamics within specialty treatment programs. In this
      introduction to the special issue, the guest editors describe a conceptual
      framework of organizational dynamics, offer an overview of the articles within
      this issue, and discuss future prospects for research.

PMID- 22154829
TI  - Colovaginoplasty using the Yang-Monti modification.
AB  - OBJECTIVE: Bowel vaginoplasty is particularly difficult in patients who are
      extremely obese or those with an android pelvis. This report evaluates the use of
      the Yang-Monti principle as a viable alternative in the reconstruction of these
      patients. METHODS: Upon retrospective chart review of patients who underwent
      bowel replacement vaginoplasty between 1980 and 2008, 4/60 were identified who
      underwent the Yang-Monti modification. The neovagina was created with an 8-10-cm
      segment of descending colon which was detubularized and then retubularized using
      the Yang-Monti principle. This was sewn in place in the perineum. Outcome was
      evaluated by physical examination data and clinical information on postoperative
      sexual function. RESULTS: Three of the four patients had an XY karyotype and an
      android pelvis, and of these two were failures of previous ileovaginoplasties and
      one was a failed colovaginoplasty. The fourth was a case of primary mullerian
      failure (XX) in a morbidly obese individual. All four were discharged without
      complication following surgery. With a median follow-up of 6 years (range 4-9),
      none showed evidence of introital stenosis or required dilation. Two were engaged
      in vaginal intercourse at last consultation, and they reported vaginal length was
      adequate. No further procedures were required in any of the patients at the end
      of the follow-up period. CONCLUSION: The Yang-Monti modification, when used as an
      adjunct to colovaginoplasty, can be an effective reconstructive technique in this
      subset of patients. It allows for lengthening of the neovagina, without
      perpetuating tension on the vascular pedicle.

PMID- 22154830
TI  - Urethral atresia and anhydramnios at 18 weeks of gestation can result in normal
      development.
AB  - INTRODUCTION: Second-trimester anhydramnios is incompatible with survival unless
      amniotic fluid volume is restored. We describe the long-term outcome of a child
      with documented anhydramnios at 17 weeks. CASE REPORT: A 28-year-old gravida II
      had anhydramnios at 17 weeks. At 19 weeks, the bladder measured 12 cm, and
      karyotype was XY. At 21 weeks, a fistula between the bladder and the amniotic
      space developed. At 36 weeks, a 2800 g boy with prune belly phenotype was
      delivered. The urachus was patent and drained urine. There was a completely
      obstructing membrane below the veru montanum and a hypoplastic urethra distal to
      it. The right kidney had no function and the left had grade V reflux. A
      P.A.D.U.A. (progressive augmentation by dilatating the urethra anterior)
      procedure was performed and the urachal fistula closed. At 6 months of age
      abdominoplasty, bilateral orchidopexy, right nephrectomy and left to right
      transuretero-ureterostomy were performed. At age 30 months he was toilet trained,
      with creatinine 0.5 mg/dl and normal growth. At 10 years of age he continues to
      be continent, with serum creatinine 0.9 mg/dl. CONCLUSION: Resolution of
      anhydramnios at 21 weeks of gestation can result in normal pulmonary function and
      acceptable renal and bladder function in childhood. Efforts to develop effective
      methods of fetal bladder decompression should continue.

PMID- 22154831
TI  - A pharmacological investigation of the venom extract of the Australian box
      jellyfish, Chironex fleckeri, in cardiac and vascular tissues.
AB  - The pharmacology of Australian box jellyfish, Chironex fleckeri, unpurified
      (crude) nematocyst venom extract (CVE) was investigated in rat isolated cardiac
      and vascular tissues and in anaesthetised rats. In small mesenteric arteries CVE
      (0.01-30 MUg/ml) caused contractions (EC(50) 1.15+/-0.19 MUg/ml) that were
      unaffected by prazosin (0.1 MUM), bosentan (10 MUM), CGRP(8-37) (1 MUM) or
      tetrodotoxin (1 MUM). Box jellyfish antivenom (5-92.6 units/ml) caused rightward
      shifts of the CVE concentration-response curve with no change in the maximum. In
      the presence of l-NAME (100 MUM) the sensitivity and maximum response to CVE were
      increased, whilst MgSO(4) (6 mM) decreased both parameters. CVE (1-10 MUg/ml)
      caused inhibition of the contractile response to electrical sympathetic nerve
      stimulation. Left atrial responses to CVE (0.001-30 MUg/ml) were bi-phasic,
      composed of an initial positive inotropy followed by a marked negative inotropy
      and atrial standstill. CVE (0.3 MUg/ml) elicited a marked decrease in right
      atrial rate followed by atrial standstill at 3 MUg/ml. These responses were
      unaffected by 1 MUM of propranolol, atropine or CGRP(8-37). Antivenom (54 and 73
      units/ml) caused rightward shifts of the CVE concentration-response curve and
      prevented atrial standstill in left and right atria. The effects of CVE do not
      appear to involve autonomic nerves, post-synaptic alpha(1)- or beta(1)
      adrenoceptors, or muscarinic, endothelin or CGRP receptors, but may occur through
      direct effects on the cardiac and vascular muscle. Box jellyfish antivenom was
      effective in attenuating CVE-induced responses in isolated cardiac and vascular
      tissues.

PMID- 22154832
TI  - Ovarian steroids increase glutamatergic related gene expression in serotonin
      neurons of macaques.
AB  - Dendritic spines are the elementary structural units of neuronal plasticity and
      their proliferation and stabilization involve components of glutamate
      neurotransmission. In a model of hormone replacement therapy (HT), we sought the
      effect of estradiol (E) and progesterone (P) on gene expression related to
      glutamate neurotransmission in a laser captured preparation enriched for
      serotonin neurons from rhesus macaques. Microarray analysis was conducted (n=2
      animals/treatment) and then confirmed for pivotal genes with qRT-PCR on
      additional laser captured material (n=3 animals/treatment). Ovariectomized rhesus
      macaques were treated with either placebo, E or E+P via Silastic implants for
      1month prior to euthanasia. The midbrain was obtained, sectioned and
      immunostained for TPH. TPH-positive neurons were laser captured using an Arcturus
      Laser Dissection Microscope (Pixel II). RNA from laser captured serotonin neurons
      (n=2 animals/treatment) was hybridized to Rhesus Affymetrix GeneChips for
      screening purposes. There was a 2-fold or greater change in the expression of 28
      probe sets related to glutamate processes in E and E+P treated animals.
      Quantitative (q) RT-PCR was conducted for 11 genes with a custom Taqman PCR array
      containing monkey specific primers and analyzed with ANOVA followed by
      Bonferroni's test. The log of the relative expression values indicated that in
      general, the responses to E and E+P were similar. Comparison of the relative
      expression or log relative expression in Ovx-controls to combined E and E+P
      treated groups with t-tests showed a significant increase in AMPA1 (GRIA1), AMPA2
      (GRIA2), AMPA4 (GRIA4), NMDA2a (GRIN2A), metabotrophic glutamate receptor (GRM1),
      glutamine synthetase (GLUL), glutamate dehydrogenase (GLUD), glutamate cysteine
      ligase modifier subunit (GCLM), the glutamate transporter 2 (SLC1A2) and the
      glutamate transporter 3 (SLC1A3) with steroid treatment. There was no effect of
      steroid treatment on gene expression of the glutamate cysteine ligase catalytic
      subunit (GCLC). These data suggest that ovarian steroids target gene expression
      of ionotrophic and metabotrophic glutamate receptors in serotonin neurons. These
      receptors are present on dendritic spines and are necessary for spine maturation.
      The mRNAs coding for glutamate-related enzymes and transporters are likely
      derived from astrocytes or glutamate-containing terminals. Their induction by
      ovarian steroids indicates a complex upregulation of multiple components in the
      glutamate cycle and antioxidation, in addition to spine proliferation.

PMID- 22154833
TI  - Synthesis and in vitro antimycobacterial activity of compounds derived from (R)-
      and (S)-2-amino-1-butanol - The crucial role of the configuration.
AB  - The synthesis of 47 structurally diverse compounds incorporating the (R)-2-amino
      1-butanol motif has been realized. Ten of these compounds were found to exhibit
      in vitro specific activity against Mycobacterium tuberculosis H37Rv in a MIC
      range of 0.65 MUM-14.03 MUM. Five of the most active compounds 11, 22, 23, 31 and
      42 (5.7-11.1 fold more active than ethambutol) can be outlined with very low
      cytotoxicity towards human embryonal kidney non-tumour cells (SI ranging from
      91.2 to 375.4). For the purpose of comparison the (S)-enantiomers of these most
      active compounds have been synthesized and evaluated towards M. tuberculosis
      H(37)Rv showing no activity even at 20-32 fold higher concentrations.

PMID- 22154834
TI  - Structure-activity relationship of salicylic acid derivatives on inhibition of
      TNF-alpha dependent NFkappaB activity: Implication on anti-inflammatory effect of
      N-(5-chlorosalicyloyl)phenethylamine against experimental colitis.
AB  - To develop a more potent NFkappaB inhibitor from salicylic acid which is known to
      inhibit activity of NFkappaB, a transcription factor regulating genes involved in
      immunity, inflammation and tumorigenesis, derivatives of salicylic acid (SA)
      where the 5 position, carboxyl or hydroxyl group was modified were treated in
      HCT116 cells transfected with an NFkappaB dependent luciferase gene and LPS
      stimulated RAW264.7 cells. Amidation of the carboxylic group or substitution of
      chlorine at the 5 position increased the ability of SA to suppress the expression
      of NFkappaB dependent luciferase and inducible nitric oxide synthase, a product
      of an NFkappaB target gene. Moreover, simultaneous amidation and chlorination of
      SA (5-chlorosalicylamide; 5-CSAM) conferred an additive NFkappaB inhibitory
      activity on SA. To further enhance the inhibitory activity, N-modification was
      imposed on 5-CSAM. N-(5-chlorosalicyloyl)phenethylamine (5-CSPA), N-(5
      chlorosalicyloyl)3-phenylpropylamine (5-CSPPA) and N-(5-chlorosalicyloyl)4
      hydroxyphenylethylamine (5-CSHPA) showed greater potencies for inhibiting
      NFkappaB activity than other derivatives. Their IC(50)s' in the luciferase assay
      measured 15MUM (5-CSPA), 17MUM (5-CSPPA) and 91MUM (5-CSHPA). Rectal
      administration of 5-CSPA ameliorated TNBS-induced rat colitis, which was more
      effective than a conventional drug, 5-aminosalicylic acid. These data may provide
      useful information for development of a therapeutic agent for treatment of
      diseases where NFkappaB plays a critical role in the pathogenic progresses.

PMID- 22154835
TI  - Synthesis, antimicrobial, anticancer evaluation and QSAR studies of 6-methyl-4-[1
      (2-substituted-phenylamino-acetyl)-1H-indol-3-yl]-2-oxo/thioxo-1,2,3,4
      tetrahydropyrimidine-5-carboxylic acid ethyl esters.
AB  - A series of 6-methyl-4-[1-(2-substituted-phenylamino-acetyl)-1H-indol-3-yl]-2
      oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl esters (1-16)
      were synthesized and evaluated in vitro for their antimicrobial and anticancer
      potential. 6-Methyl-4-{1-[2-(4-nitro-phenylamino)-acetyl]-1H-indol-3-yl}-2-thioxo
      1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester (15, pMIC(ec) = 2.50
      MUM/mL) was found to be almost equipotent to the standard drug, norfloxacin
      (pMIC(ec) = 2.61 MUM/mL) against Escherichia coli and emerged as most potent
      antimicrobial agent (pMIC(am) = 1.84 MUM/mL). 4-{1-[2-(2-Chloro-4-nitro
      phenylamino)-acetyl]-1H-indol-3-yl}-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5
      carboxylic acid ethyl ester (4, IC(50) = 5 MUg/mL) was more potent than the
      standard drug 5-fluorouracil (IC(50) = 6 MUg/mL) against HCT-116 a colon cancer
      cell line, and emerged as the most potent anticancer agent. The QSAR studies
      demonstrated the importance of topological parameter, Balaban index (J) followed
      by lipophillic parameter, log P in describing the antimicrobial activity of the
      synthesized compounds.

PMID- 22154836
TI  - Plant sterols and host plant suitability for generalist and specialist
      caterpillars.
AB  - Insects, unlike plants and vertebrates, lack the ability to biosynthesize
      sterols. Cholesterol is typically the most common sterol found in plant-feeding
      insects, but it is rarely found in plants above trace levels, so plant-feeding
      insects must produce the cholesterol they need by metabolizing the sterols found
      in the plants they eat. Plant-feeding insects are, however, often limited in
      terms of which sterols can be converted to cholesterol. In the current study we
      used a transgenic tobacco plant line that displays high levels of atypical plant
      steroids, specifically stanols and ketone-steroids, to explore how novel steroid
      structural features affect performance in three economically important
      caterpillars (Heliothis virescens, Spodoptera exigua, and Manduca sexta). For
      each species we measured pupation success, larval development, pupal mass, pupal
      development, and eclosion success. For the two generalists species (H. virescens
      and S. exigua) we also measured egg production and egg viability. We then used
      these eggs to replicate the experiment, so that we could examine the effect of
      parental steroid dietary history on survival, growth and reproduction of 2nd
      generation individuals. Significant negative effects of novel steroids on larval
      and pupal performance were observed for each caterpillar in the first generation,
      although these were often subtle, and were not consistent between the three
      species. In the second generation, larval survival estimated by 'pupation
      number/plant' on the tobacco plants with novel steroids was significantly
      reduced, while eclosion success was significantly lower for H. virescens. With
      respect to adult reproduction (i.e. egg production and egg viability) there were
      no observed differences in the first generation, but novel steroids significantly
      negatively impacted reproduction in the second generation. The findings from this
      study, when integrated into a simple population growth model, demonstrate the
      potential in using plants with modified steroids as a novel approach to manage
      populations of economically important caterpillar species.

PMID- 22154837
TI  - ESAT-6 induced COX-2 expression involves coordinated interplay between PI3K and
      MAPK signaling.
AB  - Macrophages, as sentinels of robust host immunity, are key regulators of innate
      immune responses against invading mycobacteria; however, pathogenic mycobacteria
      survive in the infected host by subverting host innate immunity. Infection
      dependent expression of early secreted antigenic target protein 6 (ESAT-6) by
      Mycobacterium tuberculosis is strongly correlated with subversion of innate
      immune responses against invading mycobacteria. As a part of multifaceted
      immunity to mycobacterial infection, induced expression of cyclooxygenase-2 (COX
      2) may act as an important influencing factor towards effective host immunity. In
      the current investigation, we demonstrate that ESAT-6 triggers COX-2 expression
      both in vitro and in vivo in a TLR2 dependent manner. Signaling perturbation data
      suggest that signaling dynamics of PI3K and p38 and JNK1/2 MAPK assume critical
      importance in ESAT-6 triggered expression of COX-2 in macrophages. Interestingly,
      ESAT-6 triggered PI3K-MAPK signaling axis holds the capacity to regulate
      coordinated activation of NF-kappaB and AP-1. Overall, current investigation
      provides mechanistic insights into ESAT-6 induced COX-2 expression and unravels
      TLR2 mediated interplay of PI3K and MAPK signaling axis as a rate-determining
      step during intricate host immune responses. These findings would serve as a
      paradigm to understand pathogenesis of mycobacterial infection and clearly pave a
      way towards development of novel therapeutics.

PMID- 22154838
TI  - k-Neighborhood decentralization: a comprehensive solution to index the UMLS for
      large scale knowledge discovery.
AB  - The Unified Medical Language System (UMLS) is the largest thesaurus in the
      biomedical informatics domain. Previous works have shown that knowledge
      constructs comprised of transitively-associated UMLS concepts are effective for
      discovering potentially novel biomedical hypotheses. However, the extremely large
      size of the UMLS becomes a major challenge for these applications. To address
      this problem, we designed a k-neighborhood Decentralization Labeling Scheme
      (kDLS) for the UMLS, and the corresponding method to effectively evaluate the
      kDLS indexing results. kDLS provides a comprehensive solution for indexing the
      UMLS for very efficient large scale knowledge discovery. We demonstrated that it
      is highly effective to use kDLS paths to prioritize disease-gene relations across
      the whole genome, with extremely high fold-enrichment values. To our knowledge,
      this is the first indexing scheme capable of supporting efficient large scale
      knowledge discovery on the UMLS as a whole. Our expectation is that kDLS will
      become a vital engine for retrieving information and generating hypotheses from
      the UMLS for future medical informatics applications.

PMID- 22154840
TI  - Longitudinal effects of fat and lean mass on bone accrual in infants.
AB  - There are conflicting reports on the influence of lean and fat mass on bone
      accrual during childhood. No infant's studies have been reported that describe
      the influence of changes in body composition with changes in bone accrual during
      the first year of life. The objective of this research was to test the hypothesis
      that greater gains in lean mass will have a positive effect on bone mineral
      content (BMC) accrual, while greater gains in fat mass will have a negative
      effect on BMC accrual in infants. Longitudinal data from 3 previous infant
      studies were used. Linear mixed models, adjusting for age, sex, dietary calcium,
      and length were used to investigate longitudinal and cross-sectional associations
      between total body BMC and lean and fat mass in the individual studies and in a
      combined analysis. In both individual and combined analyses, we found that lean
      and fat mass were positively associated with whole body BMC accrual (all,
      P<0.001). The cross-sectional association of BMC and dietary calcium was negative
      in one study (P<0.05). No differences in BMC change between sexes were observed
      in three studies. Our results showed positive cross-sectional and longitudinal
      associations between total body BMC and lean mass in infants. In contradiction to
      our hypothesis for fat mass, we found a positive cross-sectional and longitudinal
      association between total body BMC and fat mass in infants.

PMID- 22154839
TI  - Physical activity, body mass index and bone mineral density-associations in a
      prospective population-based cohort of women and men: the Canadian Multicentre
      Osteoporosis Study (CaMos).
AB  - BACKGROUND: Physical activity (PA) is an important modifiable risk factor for
      both bone mineral density (BMD) and body mass index (BMI). However, BMI is itself
      strongly predictive of BMD. Our aim was to determine the association between PA
      and BMD, with consideration of BMI as a potential mediating factor. METHODS: The
      Canadian Multicentre Osteoporosis Study (CaMos) is a population-based prospective
      cohort study of Canadian women and men. PA was determined from interviewer
      administered questionnaires at baseline and Year 5 and summarized as daily energy
      expenditure in total metabolic equivalents of the task multiplied by minutes/day
      (MET*m/d). Height, weight, and total hip and lumbar spine BMD were measured at
      baseline and Year 5. General linear models assessed relationships between PA and
      BMD, both cross-sectionally (baseline PA with baseline BMD) and longitudinally
      (average PA and change in PA with change in BMD). BMI was considered as a
      mediating factor. Potential confounders included age, center, education, caffeine
      intake, alcohol exposure, smoking history, history of weight-cycling, age at
      menarche, past use of oral contraceptives, history of >3 months missed
      menstruation, menopausal status, and antiresorptive use, as relevant. RESULTS:
      The study included 2855 men and 6442 women. PA was inversely associated with BMI
      at baseline, and an increase in PA between baseline and Year 5 was associated
      with a decrease in BMI, with 0.41 (95% CI: 0.22, 0.60) kg/m(2) loss per 1000
      MET*m/d increase (in men) and 0.40 (95% CI: 0.23, 0.57) kg/m(2) loss per 1000
      MET*m/d increase (in women). BMI was strongly associated with BMD, both cross
      sectionally and longitudinally. However, increased PA was associated with a small
      increase in total hip BMD, 0.004 (95% CI: 0.000-0.008) g/cm(2) per 1000 MET*m/d
      (in men) and 0.003 (95% CI: 0.000-0.007) g/cm(2) per 1000 MET*m/d (in women).
      Average PA was associated with an increase in lumbar spine BMD in women, but not
      in men; it was not associated with change in total hip BMD in either sex.
      CONCLUSION: Increased PA is associated with an increase in BMD and a concomitant
      decrease in BMI. These findings suggest that population-level interventions to
      increase PA would favorably impact bone and other health outcomes.

PMID- 22154841
TI  - Bone turnover markers in peripheral blood and marrow plasma reflect trabecular
      bone loss but not endocortical expansion in aging mice.
AB  - We examined age-related changes in biochemical markers and regulators of
      osteoblast and osteoclast activity in C57BL/6 mice to assess their utility in
      explaining age-related changes in bone. Several recently discovered regulators of
      osteoclasts and osteoblasts were also measured to assess concordance between
      their systemic levels versus their levels in marrow plasma, to which bone cells
      are directly exposed. MicroCT of 6-, 12-, and 24-month-old mice indicated an
      early age-related loss of trabecular bone volume and surface, followed by
      endocortical bone loss and periosteal expansion. Trabecular bone loss temporally
      correlated with reductions in biomarkers of bone formation and resorption in both
      peripheral blood and bone marrow. Endocortical bone loss and periosteal bone gain
      were not reflected in these protein biomarkers, but were well correlated with
      increased expression of osteocalcin, rank, tracp5b, and cathepsinK in RNA
      extracted from cortical bone. While age-related changes in bone turnover markers
      remained concordant in blood versus marrow, aging led to divergent changes in
      blood versus marrow for the bone cell regulators RANKL, OPG, sclerostin, DKK1,
      and serotonin. Bone expression of runx2 and osterix increased progressively with
      aging and was associated with an increase in the number of osteoprogenitors and
      osteoclast precursors. In summary, levels of biochemical markers of bone turnover
      in blood and bone marrow plasma were predictive of an age-related loss of
      trabecular surfaces in adult C57BL/6 mice, but did not predict gains in cortical
      surfaces resulting from cortical expansion. Unlike these turnover markers, a
      panel of bone cell regulatory proteins exhibited divergent age-related changes in
      marrow versus peripheral blood, suggesting that their circulating levels may not
      reflect local levels to which osteoclasts and osteoblasts are directly exposed.

PMID- 22154842
TI  - Can immune-related genotypes illuminate the immunopathogenesis of cytomegalovirus
      disease in human immunodeficiency virus-infected patients?
AB  - Most human immunodeficiency virus (HIV) patients are seropositive for
      cytomegalovirus (CMV) but a smaller proportion experience end-organ disease. This
      observation may reflect variations in genes affecting inflammatory and natural
      killer cell responses. DNA samples were collected from 240 HIV-infected patients
      followed at the University Hospitals/Case Medical Center (Cleveland, OH) between
      1993 and 2008. Seventy-eight patients (African Americans = 41, Caucasians = 37)
      experienced CMV disease. Genotypes were determined using allele-specific
      fluorescent probes or multiplex polymerase chain reaction sequence-specific
      primers. IL12B3'UTR*(1) and SLC11A1 D543N*(1,2) were associated with CMV disease
      in African American patients (p = 0.04 and p = 0.02, respectively). IL10
      1082*(1,2) and LILRB1 I142T*(1) were associated with CMV disease in Caucasians (p
      = 0.02 and p = 0.07, respectively). DARC T-46C*(1) and CD14 C-159T*(2) were
      associated with low nadir CD4(+) T cell counts in African American patients (p =
      0.002 and p = 0.01, respectively). Caucasian patients carrying TNFA-308*2, TNFA
      1031*(2), IL2-330*(1), CCL2-2518*(2), or LILRB1 I142T*(1) had significantly lower
      nadir CD4(+) T cells in a bootstrapped multivariable model (p = 0.006-0.02). In
      general, polymorphisms associated with CMV disease and CD4(+) T cell counts were
      distinct in Caucasian and African American patients in the United States. The
      LILRB1 I142T polymorphism was associated with both CMV disease and low nadir
      CD4(+) T cell counts in Caucasians, but the clearest determinant of low nadir
      CD4(+) T cell count in African American patients was DARC T-46C.

PMID- 22154843
TI  - A systematic review of the influence on alcohol use of community level
      availability and marketing of alcohol.
AB  - PURPOSE: Exposure to a high number of alcohol outlets and adverts within a
      community may lead to higher alcohol use by local residents. The aim of this
      systematic review was to explore evidence on the influence on alcohol use of
      community level availability and marketing of alcohol. RESULTS: 26 studies met
      the eligibility criteria. While the findings were not conclusive, there was some
      indication that higher outlet density and greater exposure to advertising in a
      local community may be associated with an increase in alcohol use, particularly
      among adolescents. CONCLUSIONS: This review disentangled the existing evidence on
      the overall relationships between availability, marketing and alcohol use at a
      community level. Further studies are required to better understand the influence
      of these factors on alcohol use.

PMID- 22154844
TI  - Knock-down of endothelial connexins impairs angiogenesis.
AB  - Connexins (Cx) are suggested to play important roles in growth and
      differentiation. Aim of our study was to investigate the role of endothelial Cx
      in the angiogenic process. Several parameters of angiogenesis were assessed in 18
      h Matrigel in vitro angiogenesis assays with human umbilical vein endothelial
      cells (HUVEC). Prior to culture on Matrigel cells were treated with nicotine or
      the gap junction inhibitor palmitoleic acid (PA), or siRNA-knock-down of either
      Cx37, Cx40 or Cx43 was performed. Changes in Cx expression and their effects on
      gap-junctional communication were investigated using immunofluorescence
      microscopy, Western blot and Lucifer Yellow dye transfer. Knock-down of each Cx
      isoform significantly reduced the amount of specific Cx protein in HUVEC. Cx
      knock-down as well as treatment with PA impaired intercellular communication via
      gap junctions and diminished significantly the number of capillary branches.
      Knock-down of Cx43 and Cx40 or treatment with PA reduced complexity pattern in
      the angiogenesis assay. Nicotine significantly reduced expression of Cx43 and
      Cx37 as well as average length of capillary branches, number of branches and
      pattern in the Matrigel assay. We can conclude that connexins are involved in
      angiogenesis, in particular in branch formation. This can partly explain the
      changes in angiogenesis seen under nicotine treatment.

PMID- 22154846
TI  - The apparent hysteresis in hormone-agonist relationships.
AB  - It has been noted in multiple studies that the calcium-PTH axis, among others, is
      subject to an apparent hysteresis. We sought to explain a major component of the
      observed phenomenon by constructing a simple mathematical model of a hormone and
      secretagogue system with concentration dependent secretion and containing two
      delays. We constructed profiles of the hormone-agonist axis in this model via
      four types of protocols, three of which emulating experiments from the
      literature, and observed a delay- and load-dependent hysteresis that is an
      expected mathematical artifact of the system described. In particular, the delay
      associated with correction allows for over-secretion of the hormone influencing
      the corrective mechanism; thus rate dependence is an artifact of the corrective
      mechanism, not a sensitivity of the gland to the magnitude of change. From these
      observations, the detected hysteresis is due to delays inherent in the systems
      being studied, not in the secretory mechanism.

PMID- 22154845
TI  - Anti-ischemic effects of multivalent dendrimeric A3 adenosine receptor agonists
      in cultured cardiomyocytes and in the isolated rat heart.
AB  - Adenosine released during myocardial ischemia mediates cardioprotective
      preconditioning. Multivalent drugs covalently bound to nanocarriers may differ
      greatly in chemical and biological properties from the corresponding monomeric
      agents. Here, we conjugated chemically functionalized nucleosides to
      poly(amidoamine) (PAMAM) dendrimeric polymers and investigated their effects in
      rat primary cardiac cell cultures and in the isolated heart. Three conjugates of
      A3 adenosine receptor (AR) agonists, chain-functionalized at the C2 or N6
      position, were cardioprotective, with greater potency than monomeric agonist Cl
      IB-MECA. Multivalent amide-linked MRS5216 was selective for A1 and A3ARs, and
      triazole-linked MRS5246 and MRS5539 (optionally containing fluorescent label)
      were A3AR-selective. The conjugates protected ischemic rat cardiomyocytes, an
      effect blocked by an A3AR antagonist MRS1523, and isolated hearts with
      significantly improved infarct size, rate of pressure product, and rate of
      contraction and relaxation. Thus, strategically derivatized nucleosides tethered
      to biocompatible polymeric carriers display enhanced cardioprotective potency via
      activation of A3AR on the cardiomyocyte surface.

PMID- 22154847
TI  - Lung histopathological findings in fatal pandemic influenza A (H1N1).
AB  - OBJECTIVE: To describe the lung pathological changes in influenza A (H1N1) viral
      pneumonia. We studied morphological changes, nitro-oxidative stress and the
      presence of viral proteins in lung tissue. METHODS AND PATIENTS: Light microscopy
      was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1)
      viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine,
      inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for
      analysis under confocal microscopy) was also studied in lung tissue specimens.
      RESULTS: Age ranged from 15 to 50 years. Three patients were women, and 5 had
      preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5
      cases (as evidenced by hyaline membrane formation, alveolo-capillary wall
      thickening and PMN infiltrates), and interstitial fibrosis in one case. In the
      fluorescence studies there were signs of oxygen radical generation, increased
      NOS2 protein and protein nitration in lung tissue samples, regardless of the
      duration of ICU admission. Viral NP was found in lung tissue samples from three
      patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by
      confocal immunofluorescence microscopy. CONCLUSIONS: Lung tissue from patients
      with pandemic influenza A (H1N1) viral pneumonia shows histological findings
      consistent with DAD. Prolonged nitro-oxidative stress is present despite
      antiviral treatment. Viral proteins may remain in lung tissue for prolonged
      periods of time, lodged in macrophages and type I pneumocytes.

PMID- 22154848
TI  - Is motor cortex excitability associated with personality factors? A replication
      study.
AB  - In a previous study an association has been reported between motor cortex
      excitability, as measured by paired-pulse transcranial magnetic stimulation (TMS)
      and neuroticism of the NEO personality inventory; this correlation was carried by
      the men. The aim of the present study was to replicate these findings in a larger
      sample and with additional measures of motor cortex excitability. Eighty-nine
      healthy volunteers filled in the NEO-FFI and underwent several measures of motor
      cortex excitability (resting and active motor thresholds, double-pulse TMS with
      interstimulus intervals of 1-20ms, and cortical silent period). We did not find
      any systematic significant correlations of personality factors with motor cortex
      excitability. Dividing the samples by sex or controlling for confounders such as
      age, sex and education level by partial correlations did not reveal any
      significant associations either. Reasons for the failure of replication may
      include differences in sample characteristics, personality measures, and TMS
      methodology. However, synopsis of literature indicates that association of
      personality and motor cortex excitability might be mediated rather by state than
      by trait factors.

PMID- 22154849
TI  - A microscopic description and ultrastructural characterisation of Dientamoeba
      fragilis: an emerging cause of human enteric disease.
AB  - Dientamoeba fragilis is a pathogenic trichomonad found in the gastrointestinal
      tract of humans and is implicated as a cause of diarrhoea. Despite its discovery
      over a century ago, there has been no recent thorough description of this
      parasite by microscopy. Scanning electron microscopy, transmission electron
      microscopy, confocal and light microscopy were therefore used to characterise D.
      fragilis populations growing in xenic culture. Two different populations - smooth
      and ruffled cells - were identifiable by scanning electron microscopy. No
      flagella, pelta structures, undulating membrane or pseudocyst-like forms were
      present. The organelles in D. fragilis were analysed by transmission electron
      microscopy; like Trichomonas and Histomonas, D. fragilis contains hydrogenosomes
      that presumably represent the site of anaerobic respiration. The nuclear
      morphology of D. fragilis trophozoites grown in vitro and trophozoites from
      clinical isolates were also compared by confocal microscopy and light microscopy.
      The majority of cells grown in culture were mononucleate while most cells in
      permanent stained faecal smears were binucleate. The two nuclei of D. fragilis
      are morphologically indistinguishable and contain equivalent amounts of DNA as
      determined by DAPI staining. The approximate cell and nuclear volume of four
      isolates of D. fragilis were measured and shown to be comparable to other
      trichomonads. In addition, the discovery of a virus-like particle is reported, to
      our knowledge for the first time in D. fragilis. This study therefore provides
      extensive and novel details of the ultrastructure of a neglected protozoan
      parasite that is an emerging cause of human disease.

PMID- 22154851
TI  - Fine-scale genetic analysis of Daphnia host populations infected by two virulent
      parasites - strong fluctuations in clonal structure at small temporal and spatial
      scales.
AB  - Numerous theoretical studies suggest that parasites impose a strong selection
      pressure on their host, driving genetic changes within host populations. Yet
      evidence of this process in the wild is scarce. In the present study we surveyed,
      using high resolution microsatellite markers, the genetic structure of cyclically
      parthenogenetic Daphnia hosts within two different Daphnia communities belonging
      to the Daphnia longispina hybrid complex. One community, consisting of a single
      host species, was infected with the protozoan parasite Caullerya mesnili. The
      second community consisted of two parental Daphnia spp. and their hybrids, and
      was infected with the yeast parasite Metschnikowia. Significant differences in
      the clonal composition between random and infected sub-samples of Daphnia were
      detected on several occasions within both communities, indicating that host
      genotypes differ in resistance to both parasites. In addition, one parental
      species in the multi-taxon community was consistently under-infected, compared
      with the other taxa. Overall, our field data confirm that infection patterns are
      strongly affected by host genetic composition in various Daphnia-microparasite
      systems. Thus, parasite-driven selection operates in natural Daphnia populations
      and microparasites influence the clonal structure of host populations.

PMID- 22154852
TI  - Citreorosein, a naturally occurring anthraquinone derivative isolated from
      Polygoni cuspidati radix, attenuates cyclooxygenase-2-dependent prostaglandin D2
      generation by blocking Akt and JNK pathways in mouse bone marrow-derived mast
      cells.
AB  - In this study, we examined the effects of citreorosein (CIT), an anthraquinone
      component of Polygoni cuspidati radix (P. cuspidati, Polygonaceae), on
      cyclooxygenase (COX)-2 dependent prostaglandin (PG)D2 generation in mast cells,
      central effector cells of allergy and other inflammatory diseases. CIT strongly
      inhibited COX-2-dependent PGD2 generation in a concentration-dependent manner in
      mouse bone marrow-derived mast cells (BMMCs) stimulated with stem cell factor
      (SCF)/IL-10/LPS. In an effort to identify the mechanisms underlying the
      inhibition of COX-2-dependent PGD2 generation by CIT, we examined the effects of
      this compound on MAP kinases, Akt and NF-kappaB signaling pathways, which are
      essential for COX-2 induction. CIT inhibited nuclear translocation of the nuclear
      factor (NF)-kappaB p65 subunit and its cognate DNA-binding activity, which
      correlated with its inhibitory effects on the phosphorylation of Akt and IKK and
      subsequent phosphorylation and degradation of IkappaB. Furthermore, CIT
      significantly attenuated the DNA binding of activator protein (AP)-1 that
      regulates COX-2 expression through the reduction of the phosphorylation of c-Jun.
      Moreover, inhibition of PGD2 generation by CIT was accompanied by a decrease in
      phosphorylation of cytosolic phospholipase A2alpha. Taken together, the present
      study suggests that CIT represents a potential therapeutic approach for the
      treatment of inflammatory diseases.

PMID- 22154850
TI  - Toxoplasma and Plasmodium protein kinases: roles in invasion and host cell
      remodelling.
AB  - Some apicomplexan parasites have evolved distinct protein kinase families to
      modulate host cell structure and function. Toxoplasma gondii rhoptry protein
      kinases and pseudokinases are involved in virulence and modulation of host cell
      signalling. The proteome of Plasmodium falciparum contains a family of putative
      kinases called FIKKs, some of which are exported to the host red blood cell and
      might play a role in erythrocyte remodelling. In this review we will discuss
      kinases known to be critical for host cell invasion, intracellular growth and
      egress, focusing on (i) calcium-dependent protein kinases and (ii) the secreted
      kinases that are unique to Toxoplasma (rhoptry protein kinases and pseudokinases)
      and Plasmodium (FIKKs).

PMID- 22154853
TI  - Interaction between gamma-radiation and dietary folate starvation metabolically
      reprograms global hepatic histone H3 methylation at lysine 4 and lysine 27
      residues.
AB  - The objective of the present study was to investigate the regulatory control of
      histone H3 methylation at lysine 4 (H3K4) and lysine 27 (H3K27) residues in
      response to the effect of folate deficiency and gamma (gamma)-radiation. Male
      Swiss mice maintained on folate sufficient diet (FSD) and folate free diet (FFD)
      based on AIN-93M formula, were subjected to 2-4 Gy total body gamma-irradiation.
      There was a significant decrease in liver folate levels with concomitant
      depletion of S-adenosylmethionine (SAM) reserves. Folate deficiency and gamma
      radiation together induced H3K4 histone methyltransferase (H3K4HMTase) and
      suppressed H3K27 histone methyltransferase (H3K27HMTase) activities in a dose and
      time dependent manner. Our studies suggested radiation induced metabolic
      reprogramming of H3K4/H3K27 methylation patterns in FFD animals. We showed that
      radiation toxicity diverted one-carbon (C1) flux in FFD fed animals towards H3K4
      methylation. Present work on methylation pattern of histone lysine residues gains
      particular importance as methylation of H3K4 residues is associated with
      euchromatin while methylated H3K27 residues promote gene silencing. In
      conclusion, our study suggests that maintenance of genomic histone methylation
      under gamma-radiation stress might be a very dynamic, progressive process that
      could be modulated by dietary folate deficiency leading to formation of
      epigenetically reprogrammed cells.

PMID- 22154854
TI  - Nutritional composition and antioxidant activity of four tomato (Lycopersicon
      esculentum L.) farmer' varieties in Northeastern Portugal homegardens.
AB  - The nutritional and antioxidant composition of four tomato Portuguese farmer'
      varieties widely cultivated in homegardens was determined. The analysed
      components included macronutrients, individual profiles of sugars and fatty acids
      by chromatographic techniques, hydrophilic antioxidants such as vitamin C,
      phenolics, flavonols and anthocyanins, and lipophilic antioxidants such as
      tocopherols, beta-carotene and lycopene. Furthermore, the antioxidant activity
      was evaluated through DPPH scavenging activity, reducing power, beta-carotene
      bleaching inhibition and TBARS formation inhibition. One of the four varieties,
      which is locally known as round tomato or potato tomato, proved to be the most
      powerful in antioxidant activity (EC50 values<=1.63 mg/ml), phenolic compounds
      (phenolics 31.23 mg ClAE/g extract, flavonols 6.36 mg QE/g extract and
      anthocyanins 3.45 mg ME/g extract) and carotenoids (beta-carotene 0.51 mg/100 g
      and lycopene 9.49 mg/100 g), while the so-called yellow tomato variety revealed
      interesting nutritional composition, including higher fructose (3.42 g/100 g),
      glucose (3.18 g/100 g), alpha-linolenic acid (15.53%) and total tocopherols (1.44
      mg/100 g) levels. Overall, these farmer' varieties of garden tomato cultivated in
      the Northeastern Portuguese region could contribute as sources of important
      antioxidants related to the prevention of chronic diseases associated to
      oxidative stress, such as cancer and coronary artery disease.

PMID- 22154855
TI  - Continuous infusion of piperacillin/tazobactam in ventilator-associated
      pneumonia: a pilot study on efficacy and costs.
AB  - Ventilator-associated pneumonia (VAP) occurs in nearly one-third of mechanically
      ventilated patients in the Intensive Care Unit. Piperacillin/tazobactam (TZP) is
      currently recommended in the empirical treatment of VAP, but intermittent dosing
      may result in inadequate serum concentrations. The efficacy and costs of
      continuous infusion (CI) of TZP, using therapeutic drug monitoring for real-time
      dose adjustment, was assessed in a prospective pilot study of 16 patients with
      VAP. TZP was given as a loading dose of 2.0/0.25 g followed by a CI of 10.0/1.25g
      daily. Rapid antimicrobial susceptibility testing was used to determine the
      minimum inhibitory concentration (MIC) of the pathogens. TZP concentrations were
      determined by high-pressure liquid chromatography before and at 1, 6, 12, 24, 48,
      72 and 96 h after the onset of administration. Dosages were adjusted to maintain
      piperacillin concentrations four-fold above the MIC (T>4 * MIC) of the pathogen,
      with a maximum dose of 16.0/2.0 g. The cost of the total TZP administered was
      compared with the cost of a standard TZP regimen (16.0/2.0 g) if given over the
      same period of time. The median MIC for TZP was 1 MUg/mL (range 0.025-32 MUg/mL).
      TZP concentrations were adequate for 71% of pathogens on the first day of
      therapy. Clinical cure was achieved in 9/10 patients who had adequate drug
      concentrations and in 3/6 patients with insufficient levels. The daily dose of
      TZP received by CI was 37.5% less than that of a standard regimen, which
      corresponds to a saving of ?15 on daily therapy costs compared with the standard
      regimen. In conclusion, CI of TZP achieved optimal drug concentrations in most
      patients with VAP, with a favourable impact on costs. Adequate drug
      concentrations were achieved for MIC <= 4 MUg/mL, but higher dosages should be
      considered for the treatment of pathogens with low susceptibility thresholds.

PMID- 22154856
TI  - Efficacies of colistin and tigecycline in mice with experimental pneumonia due to
      NDM-1-producing strains of Klebsiella pneumoniae and Escherichia coli.
AB  - New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Enterobacteriaceae have
      emerged as a global threat. The aim of this study was to assess the efficacies of
      colistin and tigecycline in an experimental model of pneumonia caused by NDM-1
      producing Escherichia coli and Klebsiella pneumoniae. The susceptibilities of K.
      pneumoniae NDM, E. coli NDM and K. pneumoniae ATCC 29665 were determined using
      the broth microdilution technique. The pharmacokinetics of colistin and
      tigecycline in an experimental model of pneumonia were performed using
      immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or
      tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial
      concentrations were recorded. The strains were susceptible to colistin and
      tigecycline. The ratio of area under the concentration-time curve/minimum
      inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and
      that for tigecycline was 18.5 (K. pneumoniae NDM) and 37 (K. pneumoniae ATCC
      29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations
      of K. pneumoniae NDM and K. pneumoniae ATCC 29665 by 1.16 log colony-forming
      units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not
      significant). Tigecycline reduced K. pneumoniae NDM and K. pneumoniae ATCC 29665
      load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline
      decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g
      (P<0.05), respectively, compared with controls, and was more active than colistin
      (P<0.05). In conclusion, these results suggest that colistin is inappropriate for
      treating pneumonia due to NDM-1-producing K. pneumoniae and its efficacy was
      suboptimal against NDM-1-producing E. coli. A high tigecycline dose was
      efficacious for treating experimental pneumonia due to NDM-1-producing E. coli
      and K. pneumoniae.

PMID- 22154857
TI  - Poly(amidoamine) dendronized hollow fiber membranes: synthesis, characterization,
      and preliminary applications as drug delivery devices.
AB  - Poly(amidoamine) (PAMAM) dendrons were prepared from hollow fiber membranes (HFM)
      consisting of bromomethylated poly(2,6-dimethyl-1,4-phenylene oxide) (BPPO) in a
      stepwise manner. The prepared HFM were characterized by Fourier transform
      infrared spectroscopy, elemental analysis, and scanning electron microscopy. The
      drug loading efficiency and release behavior of the PAMAM dendronized HFM were
      evaluated using sodium salicylate, sodium methotrexate, and Congo red as model
      drugs. The results suggest that PAMAM dendronized HFM can be effectively loaded
      with a variety of drugs and prolong the release of these drugs. The drug loading
      and release characteristics of the HFM depend on the generation of PAMAM dendrons
      grafted on the membranes. The prepared PAMAM dendronized BPPO HFM are promising
      scaffolds in drug delivery and tissue engineering.

PMID- 22154858
TI  - Hydrazone self-crosslinking of multiphase elastin-like block copolymer networks.
AB  - Biosynthetic strategies for the production of recombinant elastin-like protein
      (ELP) triblock copolymers have resulted in elastomeric protein hydrogels, formed
      through rapid physical crosslinking upon warming of concentrated solutions.
      However, the strength of physically crosslinked networks can be limited, and
      options for non-toxic chemical crosslinking of these networks are not optimal. In
      this report, we modify two recombinant elastin-like proteins with aldehyde and
      hydrazide functionalities. When combined, these modified recombinant proteins
      self-crosslink through hydrazone bonding without requiring initiators or
      producing by-products. Crosslinked materials are evaluated for water content and
      swelling upon hydration, and subject to tensile and compressive mechanical tests.
      Hydrazone crosslinking is a viable method for increasing the mechanical strength
      of elastin-like protein polymers, in a manner that is likely to lend itself to
      the biocompatible in situ formation of chemically and physically crosslinked ELP
      hydrogels.

PMID- 22154859
TI  - Cell death in HeLa mediated by thermoplastic polyurethane with co-immobilized IFN
      gamma plus TNF-alpha.
AB  - In order to prohibit the toxicity of free IFN-gamma plus TNF-alpha in treating
      human cervical cancer HeLa cells, two kinds of thermoplastic polyurethane
      (polyester/polyether) biomaterials with co-immobilized IFN-gamma plus TNF-alpha
      on the surfaces are prepared. The programmed cell death of HeLa induced by these
      biomaterials is investigated. The surface modification of these biomaterials with
      co-immobilized IFN-gamma plus TNF-alpha is performed by the photo-immobilization
      method, and the surface structures are characterized by various techniques. The
      cell morphology, cell mortality, cell cycle arrest, and functional status of
      caspases, upon the treatment by these biomaterials, are characterized. The
      results show that the as-prepared biomaterials have high inhibition activity
      against the growth of HeLa cells. The HeLa cells mediated by the two kinds of
      biomaterials are mainly arrested in the G(1) phase, while those cells mediated
      directly by free IFN-gamma plus TNF-alpha are mainly arrested in the S phase. It
      is suggested that the programmed cell death mechanism induced by these two kinds
      of biomaterials is both caspase-dependent and caspase-independent. Our data
      provide the knowledge of microscopic surface structures and cell biology basis
      for synthesizing the thermoplastic polyurethane biomaterials with co-immobilized
      IFN-gamma plus TNF-alpha, which are promising for novel therapeutics (e.g. drug
      cup) design for cervical cancer patients.

PMID- 22154860
TI  - Effect of cleaning and sterilization on titanium implant surface properties and
      cellular response.
AB  - Titanium (Ti) has been widely used as an implant material due to the excellent
      biocompatibility and corrosion resistance of its oxide surface. Biomaterials must
      be sterile before implantation, but the effects of sterilization on their surface
      properties have been less well studied. The effects of cleaning and sterilization
      on surface characteristics were bio-determined using contaminated and pure Ti
      substrata first manufactured to present two different surface structures:
      pretreated titanium (PT, Ra=0.4 MUm) (i.e. surfaces that were not modified by
      sandblasting and/or acid etching); (SLA, Ra=3.4 MUm). Previously cultured cells
      and associated extracellular matrix were removed from all bio-contaminated
      specimens by cleaning in a sonicator bath with a sequential acetone-isopropanol
      ethanol-distilled water protocol. Cleaned specimens were sterilized with
      autoclave, gamma irradiation, oxygen plasma, or ultraviolet light. X-ray
      photoelectron spectroscopy (XPS), contact angle measurements, profilometry, and
      scanning electron microscopy were used to examine surface chemical components,
      hydrophilicity, roughness, and morphology, respectively. Small organic molecules
      present on contaminated Ti surfaces were removed with cleaning. XPS analysis
      confirmed that surface chemistry was altered by both cleaning and sterilization.
      Cleaning and sterilization affected hydrophobicity and roughness. These modified
      surface properties affected osteogenic differentiation of human MG63 osteoblast
      like cells. Specifically, autoclaved SLA surfaces lost the characteristic
      increase in osteoblast differentiation seen on starting SLA surfaces, which was
      correlated with altered surface wettability and roughness. These data indicated
      that recleaned and resterilized Ti implant surfaces cannot be considered the same
      as the first surfaces in terms of surface properties and cell responses.
      Therefore, the reuse of Ti implants after resterilization may not result in the
      same tissue responses as found with never-before-implanted specimens.

PMID- 22154861
TI  - Nanofiber topography and sustained biochemical signaling enhance human
      mesenchymal stem cell neural commitment.
AB  - Stem cells hold great promise in enhancing nerve regeneration. In particular,
      human mesenchymal stem cells (MSC) represent a clinically viable cell source due
      in part to their abundance and accessibility. Unfortunately, current methods to
      direct the fate of stem cells remains largely limited to biochemical-based
      approaches on two-dimensional substrates with restricted efficacies. Here we have
      evaluated a scaffold-based approach to directing stem cell differentiation. We
      demonstrate the combined effects of nanofiber topography and controlled drug
      release on enhancing MSC neural commitment. By encapsulating up to 0.3 wt.%
      retinoic acid (RA) within aligned poly(epsilon-caprolactone) (PCL) nanofibers
      (average diameter ~270 nm, AF750), sustained released of RA was obtained for at
      least 14 days (~60% released). Compared with tissue culture polystyrene (TCPS),
      the nanofiber topography arising from plain PCL nanofibers significantly up
      regulated the expressions of neural markers, Tuj-1, MAP2, GalC and RIP at the
      mRNA and protein levels. Combined with sustained drug availability, more
      significant changes in cell morphology and enhancement of neural marker
      expression were observed. In particular, scaffold-based controlled delivery of RA
      enhanced MAP2 and RIP expression compared with bolus delivery despite lower
      amounts of drug (>8 times lower). The generally higher expression of the mature
      neuronal marker MAP2 compared with glial markers at the mRNA and protein levels
      suggested an enhanced potential of MSC neuronal differentiation. In addition,
      positive staining for synaptophysin was detected only in cells cultured on
      aligned scaffolds in the presence of RA. Taken together, the results highlight
      the advantage of the scaffold-based approach in enhancing the potential of MSC
      neuronal differentiation and demonstrated the importance of the drug delivery
      approach in directing cell fate. Such biomimicking drug-encapsulating scaffolds
      may permit subsequent direct cell transplantation and provide guidance cues to
      control the fate of endogenously recruited stem cells.

PMID- 22154862
TI  - Real time assessment of surface interactions with a titanium passivation layer by
      surface plasmon resonance.
AB  - Due to the high corrosion resistance and strength to density ratio titanium is
      widely used in industry, and also in a gamut of medical applications. Here we
      report for the first time on our development of a titanium passivation layer
      sensor that makes use of surface plasmon resonance (SPR). The deposited titanium
      metal layer on the sensor was passivated in air, similarly to titanium medical
      devices. Our "Ti-SPR sensor" enables analysis of biomolecule interactions with
      the passivated surface of titanium in real time. As a proof of concept, corrosion
      of a titanium passivation layer exposed to acid was monitored in real time. The
      Ti-SPR sensor can also accurately measure the time-dependence of protein
      adsorption onto the titanium passivation layer at sub-nanogram per square
      millimeter accuracy. Besides such SPR analyses, SPR imaging (SPRI) enables real
      time assessment of chemical surface processes that occur simultaneously at
      "multiple independent spots" on the Ti-SPR sensor, such as acid corrosion or
      adhesion of cells. Our Ti-SPR sensor will therefore be very useful to study
      titanium corrosion phenomena and biomolecular titanium-surface interactions with
      application in a broad range of industrial and biomedical fields.

PMID- 22154863
TI  - Silicon-stabilized alpha-tricalcium phosphate and its use in a calcium phosphate
      cement: characterization and cell response.
AB  - alpha-Tricalcium phosphate (alpha-TCP) is widely used as a reactant in calcium
      phosphate cements. This work aims at doping alpha-TCP with silicon with a twofold
      objective. On the one hand, to study the effect of Si addition on the stability
      and reactivity of this polymorph. On the other, to develop Si-doped cements and
      to evaluate the effect of Si on their in vitro cell response. For this purpose a
      calcium-deficient hydroxyapatite was sintered at 1250 degrees C with different
      amounts of silicon oxide. The high temperature polymorph alpha-TCP was stabilized
      by the presence of silicon, which inhibited reversion of the beta->alpha
      transformation, whereas in the Si-free sample alpha-TCP completely reverted to
      the beta-polymorph. However, the beta-alpha transformation temperature was not
      affected by the presence of Si. Si-alpha-TCP and its Si-free counterpart were
      used as reactants for a calcium phosphate cement. While Si-alpha-TCP showed
      faster hydrolysis to calcium-deficient hydroxyapatite, upon complete reaction the
      crystalline phases, morphology and mechanical properties of both cements were
      similar. An in vitro cell culture study, in which osteoblast-like cells were
      exposed to the ions released by both materials, showed a delay in cell
      proliferation in both cases and stimulation of cell differentiation, more marked
      for the Si-containing cement. These results can be attributed to strong
      modification of the ionic concentrations in the culture medium by both materials.
      Ca-depletion from the medium was observed for both cements, whereas continuous Si
      release was detected for the Si-containing cement.

PMID- 22154865
TI  - Engineering hydrophobin DewA to generate surfaces that enhance adhesion of human
      but not bacterial cells.
AB  - Hydrophobins are fungal proteins with the ability to form immunologically inert
      membranes of high stability, properties that makes them attractive candidates for
      orthopaedic implant coatings. Cell adhesion on the surface of such implants is
      necessary for better integration with the neighbouring tissue; however,
      hydrophobin surfaces do not mediate cell adhesion. The aim of this project was
      therefore to investigate whether the class I hydrophobin DewA from Aspergillus
      nidulans can be functionalized for use on orthopaedic implant surfaces. DewA
      variants bearing either one RGD sequence or the laminin globular domain LG3
      binding motif were engineered. The surfaces of both variants showed significantly
      increased adhesion of mesenchymal stem cells (MSCs), osteoblasts, fibroblasts and
      chondrocytes; in contrast, the insertion of binding motifs RGD and LG3 in DewA
      did not increase Staphylococcus aureus adhesion to the hydrophobin surfaces.
      Proliferation of MSCs and their osteogenic, chondrogenic and adipogenic
      differentiation potential were not affected on these surfaces. The engineered
      surfaces therefore enhanced MSC adhesion without interfering with their
      functionality or leading to increased risk of bacterial infection.

PMID- 22154864
TI  - Mineral coatings modulate beta-TCP stability and enable growth factor binding and
      release.
AB  - beta-Tricalcium phosphate (beta-TCP) is an attractive ceramic for bone tissue
      repair because of its similar composition to bone mineral and its
      osteoconductivity. However, compared with other ceramics beta-TCP has a rapid and
      uncontrolled rate of degradation. In the current study beta-TCP granules were
      mineral coated with the aim of influencing the dissolution rate of beta-TCP, and
      also to use the coating as a carrier for controlled release of the growth factors
      recombinant human vascular endothelial growth factor (rhVEGF), modular VEGF
      peptide (mVEGF), and modular bone morphogenetic protein 2 peptide (mBMP2). The
      biomineral coatings were formed by heterogeneous nucleation in aqueous solution
      using simulated body fluid solutions with varying concentrations of bicarbonate
      (HCO(3)). Our results demonstrate that we could coat beta-TCP granules with
      mineral layers possessing different dissolution properties. The presence of a
      biomineral coating delays the dissolution rate of the beta-TCP granules. As the
      carbonate (CO(3)(2-)) content in the coating was increased the dissolution rate
      of the coated beta-TCP also increased, but remained slower than the dissolution
      of uncoated beta-TCP. In addition, we showed sustained release of multiple growth
      factors, with release kinetics that were controllable by varying the identity of
      the growth factor or the CO(3)(2-) content in the mineral coating. Released
      rhVEGF induced human umbilical vein endothelial cell (HUVEC) proliferation, and
      mVEGF enhanced migration of mouse embryonic endothelial cells in a scratch wound
      healing assay, indicating that each released growth factor was biologically
      active.

PMID- 22154866
TI  - Implementation of complementary interventions in the Netherlands: experiences of
      pioneers.
AB  - OBJECTIVE: Although many Dutch patients desire integration of complementary
      interventions in conventional healthcare, implementation is in its infancy in the
      Netherlands. The objective of this study was to describe the implementation
      process of complementary interventions in Dutch healthcare organizations.
      METHODS: Data in this qualitative study were collected in two steps: by
      questionnaires and by interviews. In five organizations the project leader and a
      professional who provides the interventions participated in the study. RESULTS:
      Main facilitators for implementation are: enthusiasm and support of colleagues;
      appreciation of patients; effectiveness of the interventions; positive
      publications in media; possibility to link the project to objectives of the
      organization; and accessibility of the interventions. Main barriers for
      implementation are: ignorance and skepticism of professionals; lack of research;
      lack of budget; lack of integration of the interventions in daily practice.
      Participants developed strategies to overcome barriers and to exploit
      facilitators. CONCLUSION: Professionals play a leading role in the implementation
      of complementary interventions in Dutch healthcare organizations. They use
      several methods to deal with facilitators and barriers. PRACTICE IMPLICATIONS:
      Organizations and professionals that aim to implement complementary interventions
      in their service may learn from experiences of pioneer organizations.

PMID- 22154867
TI  - Effectiveness of a web-based, individually tailored decision aid for depression
      or acute low back pain: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a web-based, individually tailored
      decision aid (Patient Dialogue) on depression or acute low back pain for insurees
      of a German sickness fund. METHODS: Patient Dialogue (PD) was compared to the non
      tailored Static Patient Information (SPI) in an online randomized controlled
      trial (RCT). The primary outcome was decisional conflict; secondary outcomes
      included knowledge, preparation for decision-making, preference for
      participation, involvement in decision-making, decision regret, and adherence.
      RESULTS: Out of 2480 randomized participants, 657 (26.5%) provided analyzable
      data immediately after using the system. Three months later, data from 131 (5.3%)
      participants could be included in the analysis. The PD group reported a
      significantly lower overall decisional conflict than the SPI group (38.7 vs.
      45.1; p=0.028 via multiple imputation estimator). The largest standardized effect
      (Cohen's d 0.56) resulted from the preparation for decision-making (PD 59.4 vs.
      SPI 46.8; p<0.001). CONCLUSION: PD may be an effective tool to reduce decisional
      conflict and prepare participants for treatment decision-making. However, the
      large dropout rate needs to be taken into account. PRACTICE IMPLICATIONS: This
      study shows how a health insurance fund can support shared decision-making and
      how a decision aid can be evaluated in a RCT under routine care conditions.

PMID- 22154868
TI  - Evidence and consensus based GKJR guidelines for the treatment of juvenile
      idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in
      children and adolescents. Immunomodulatory drugs are used frequently in its
      treatment. Using the nominal group technique (NGT) and Delphi method, we created
      a multidisciplinary, evidence- and consensus-based treatment guideline for JIA
      based on a systematic literature analysis and three consensus conferences.
      Conferences were headed by a professional moderator and were attended by
      representatives who had been nominated by their scientific societies or
      organizations. 15 statements regarding drug therapy, symptomatic and surgical
      management were generated. It is recommended that initially JIA is treated with
      NSAID followed by local glucocorticoids and/or methotrexate if unresponsive.
      Complementing literature evidence with long-standing experience of caregivers
      allows creating guidelines that may potentially improve the quality of care for
      children and adolescents with JIA.

PMID- 22154869
TI  - Fate and biological effects of silver, titanium dioxide, and C60 (fullerene)
      nanomaterials during simulated wastewater treatment processes.
AB  - As engineered nanomaterials (NMs) become used in industry and commerce their
      loading to sewage will increase. In this research, sequencing batch reactors
      (SBRs) were operated with hydraulic (HRT) and sludge (SRT) retention times
      representative of full-scale biological WWTPs for several weeks. Under
      environmentally relevant NM loadings and biomass concentrations, NMs had
      negligible effects on ability of the wastewater bacteria to biodegrade organic
      material, as measured by chemical oxygen demand (COD). Carboxy-terminated polymer
      coated silver nanoparticles (fn-Ag) were removed less effectively (88% removal)
      than hydroxylated fullerenes (fullerols; >90% removal), nano TiO(2) (>95%
      removal) or aqueous fullerenes (nC(60); >95% removal). Experiments conducted over
      4 months with daily loadings of nC(60) showed that nC(60) removal from solution
      depends on the biomass concentration. Under conditions representative of most
      suspended growth biological WWTPs (e.g., activated sludge), most of the NMs will
      accumulate in biosolids rather than in liquid effluent discharged to surface
      waters. Significant fractions of fn-Ag were associated with colloidal material
      which suggests that efficient particle separation processes (sedimentation or
      filtration) could further improve removal of NM from effluent.

PMID- 22154870
TI  - Nanofiltration and nanostructured membranes--should they be considered
      nanotechnology or not?
AB  - Nanofiltration is frequently associated with nanotechnology - obviously because
      of its name. However, the term "nano" in nanofiltration refers - according to the
      definition of the International Union of Pure and Applied Chemistry (IUPAC) - to
      the size of the particles rejected and not to a nanostructure as defined by the
      International Organisation of Standardisation (ISO) in the membrane. Evidently,
      the approach to standardisation of materials differs significantly between
      membrane technology and nanotechnology which leads to considerable confusion and
      inconsistent use of the terminology. There are membranes that can be
      unambiguously attributed to both membrane technology and nanotechnology such as
      those that are functionalized with nanoparticles, while the classification of
      hitherto considered to be conventional membranes as nanostructured material is
      questionable. A driving force behind the efforts to define nanomaterials is not
      least the urgent need for the regulation of the use of nanomaterials. Since risk
      estimation is the basis for nanotechnology legislation, the risk associated with
      nanomaterials should also be reflected in the underlying standards and
      definitions. This paper discusses the impacts of the recent attempts to define
      nanomaterials on membrane terminology in the light of risk estimations and the
      need for regulation.

PMID- 22154871
TI  - Biomineralization based remediation of As(III) contaminated soil by Sporosarcina
      ginsengisoli.
AB  - Arsenic is a highly toxic metalloid and has posed high risk to the environment.
      As(III) is highly mobile in soil and leached easily into groundwater. The current
      remediation techniques are not sufficient to immobilize this toxic element. In
      the present study, an As(III) tolerant bacterium Sporosarcina ginsengisoli CR5
      was isolated from As contaminated soil of Urumqi, China. We investigated the role
      of microbial calcite precipitated by this bacterium to remediate soil
      contaminated with As(III). The bacterium was able to grow at high As(III)
      concentration of 50mM. In order to obtain arsenic distribution pattern, five
      stage soil sequential extraction was carried out. Arsenic mobility was found to
      significantly decrease in the exchangeable fraction of soil and subsequently the
      arsenic concentration was markedly increased in carbonated fraction after
      bioremediation. Microbially induced calcite precipitation (MICP) process in
      bioremediation was further confirmed by ATR-FTIR and XRD analyses. XRD spectra
      showed presence of various biomineralization products such as calcite,
      gwihabaite, aragonite and vaterite in bioremediated soil samples. The results
      from this study have implications that MICP based bioremediation by S.
      ginsengisoli is a viable, environmental friendly technology for remediation of
      the arsenic contaminated sites.

PMID- 22154872
TI  - Investigation of strontium sorption onto Kula volcanics using Central Composite
      Design.
AB  - In performance assessment studies, the uptake of the radioactive elements by rock
      formations play an important role in retarding their aqueous phase migration.
      Sorption studies of radionuclides have been conducted to obtain data on the
      distribution coefficient (K(d)) that is as an input parameter in the performance
      assessment of the geological disposal of radioactive wastes. In this work,
      sorption experiments were studied in a batch sorption system using Sr(NO(3))(2)
      solution on non-treated and HCl-treated Kula volcanics. The distribution
      coefficient (K(d)) values of Sr(2+) derived from batch experiments were used to
      evaluate the migration behavior of Sr(2+). Central Composite Design was used in
      the experiments. Sr sorption was studied as a function of pH, temperature,
      initial concentration of adsorbate and contact time. The results show that the
      K(d) values are higher at pH 7-9 which is the pH range of the natural waters. The
      kinetic data conformed better to the pseudo-second-order equation. Thermodynamic
      parameters DeltaH degrees , DeltaS degrees  and DeltaG degrees  were estimated
      and these parameters show that adsorption is endothermic. The correlation
      coefficients indicate that the Langmuir model fits better for the strontium
      sorption onto non-treated and HCl-treated Kula volcanics with monolayer
      capacities as 2.04 and 1.72 mg/g, respectively.

PMID- 22154873
TI  - Predictive information processing in the brain: errors and response monitoring.
AB  - The monitoring of one's own actions is essential for adjusting behavior. In
      particular, response errors are important events that require behavioral
      adjustments. Correct and incorrect responses, as well as feedback to responses,
      are followed by brain activity originating mainly in the anterior cingulate,
      which can be measured with fMRI and event-related potential (ERP) techniques.
      After each response a small negativity (Nc or CRN) is elicited in the ERP, which
      is strongly enhanced in incorrect trials (Ne or ERN). Following feedback stimuli
      that signal a negative outcome of an action, a similar negativity, the feedback
      related negativity (FRN) is elicited. Recently it has been shown that these
      neurophysiological correlates of response monitoring and evaluation can be
      classified even on the single-trial level in the EEG and thus could be utilized
      not only to distinguish between correct and erroneous actions, but also can be
      used online for a wide range of applications such as prediction of clinical
      outcomes or brain computer interfaces.

PMID- 22154874
TI  - A pilot project in distance education: nurse practitioner students' experience of
      personal video capture technology as an assessment method of clinical skills.
AB  - This paper reports on a pilot project aimed at exploring postgraduate distance
      students' experiences using personal video capture technology to complete
      competency assessments in physical examination. A pre-intervention survey
      gathered demographic data from nurse practitioner students (n=31) and measured
      their information communication technology fluency. Subsequently, thirteen (13)
      students were allocated a hand held video camera to use in their clinical
      setting. Those participating in the trial completed a post-intervention survey
      and further data were gathered using semi-structured interviews. Data were
      analysed by descriptive statistics and deductive content analysis, and the
      Unified Theory of Acceptance and Use of Technology (Venkatesh et al., 2003) were
      used to guide the project. Uptake of the intervention was high (93%) as students
      recognised the potential benefit. Students were video recorded while performing
      physical examinations. They described high level of stress and some anxiety,
      which decreased rapidly while assessment was underway. Barriers experienced were
      in the areas of facilitating conditions (technical character e.g. upload of
      files) and social influence (e.g. local ethical approval). Students valued the
      opportunity to reflect on their recorded performance with their clinical mentors
      and by themselves. This project highlights the demands and difficulties of
      introducing technology to support work-based learning.

PMID- 22154875
TI  - Expression and purification of non-N-glycosylated porcine interleukin 3 in yeast
      Pichia pastoris.
AB  - Yeast Pichia pastoris has been widely utilized to express heterologous
      recombinant proteins. P. pastoris expressed recombinant porcine interleukin 3
      (IL3) has been used for porcine stem cell mobilization in allo-hematopoietic cell
      transplantation models and pig-to-primate xeno-hematopoietic cell transplantation
      models in our lab for many years. Since the yeast glycosylation mechanism is not
      exactly the same as those of other mammalian cells, P. pastoris expressed high
      mannose glycoprotein porcine IL3 has been shown to result in a decreased serum
      half-life. Previously this was avoided by separation of the non-glycosylated
      porcine IL3 from the mixture of expressed glycosylated and non-glycosylated
      porcine IL3. However, this process was very inefficient and lead to a poor yield
      following purification. To overcome this problem, we engineered a non-N
      glycosylated version of porcine IL3 by replacing the four potential N
      glycosylation sites with four alanines. The codon-optimized non-N-glycosylated
      porcine IL3 gene was synthesized and expressed in P. pastoris. The expressed non
      N-glycosylated porcine IL3 was captured using Ni-Sepharose 6 fast flow resin and
      further purified using strong anion exchange resin Poros 50 HQ. In vivo
      mobilization studies performed in our research facility demonstrated that the non
      N-glycosylated porcine IL3 still keeps the original stem cell mobilization
      function.

PMID- 22154876
TI  - Tumor invasion margin on the Riemannian space of brain fibers.
AB  - Glioma is one of the most challenging types of brain tumors to treat or control
      locally. One of the main problems is to determine which areas of the apparently
      normal brain contain glioma cells, as gliomas are known to infiltrate several
      centimeters beyond the clinically apparent lesion that is visualized on standard
      Computed Tomography scans (CT) or Magnetic Resonance Images (MRIs). To ensure
      that radiation treatment encompasses the whole tumor, including the cancerous
      cells not revealed by MRI, doctors treat the volume of brain that extends 2cm out
      from the margin of the visible tumor. This approach does not consider varying
      tumor-growth dynamics in different brain tissues, thus it may result in killing
      some healthy cells while leaving cancerous cells alive in the other areas. These
      cells may cause recurrence of the tumor later in time, which limits the
      effectiveness of the therapy. Knowing that glioma cells preferentially spread
      along nerve fibers, we propose the use of a geodesic distance on the Riemannian
      manifold of brain diffusion tensors to replace the Euclidean distance used in the
      clinical practice and to correctly identify the tumor invasion margin. This
      mathematical model results in a first-order Partial Differential Equation (PDE)
      that can be numerically solved in a stable and consistent way. To compute the
      geodesic distance, we use actual Diffusion Weighted Imaging (DWI) data from 11
      patients with glioma and compare our predicted infiltration distance map with
      actual grwoth in follow-up MRI scans. Results show improvement in predicting the
      invasion margin when using the geodesic distance as opposed to the 2cm
      conventional Euclidean distance.

PMID- 22154877
TI  - Optimisation of multiple W/O/W nanoemulsions for dermal delivery of aciclovir.
AB  - In the present study multiple W/O/W nanoemulsions were optimised for the dermal
      application of the antiviral drug aciclovir. The phase inversion temperature
      method was employed to prepare the formulations without the input of high
      pressure. During formulation design the ethoxylated surfactants were varied and
      if possible partly replaced by natural sugar surfactants. Multiple nanoemulsions
      with mean droplet sizes around 100 nm and polydispersity indices below 0.1 were
      prepared. At room temperature, they exhibited excellent physicochemical stability
      over an observation period of 6 months. Furthermore, cryo electron microscopy
      gave an insight into the microstructure of the multiple nanoemulsions. Moreover,
      the formulations' interaction with skin was analysed by ATR-FTIR. In Franz-type
      diffusion cell and tape stripping experiments aciclovir showed satisfying skin
      permeation from the novel nanoemulsions.

PMID- 22154878
TI  - Parasites and pathogens of the endosymbiotic pea crab (Pinnotheres pisum) from
      blue mussels (Mytilus edulis) in England.
AB  - A histopathological survey of the commensal pea crab (Pinnotheres pisum) from the
      mantle cavities of blue mussels (Mytilus edulis) has been conducted. A total of
      266 pea crabs from eight sites around the English coastline were examined. Of
      these, 82 were negative for any visible infections by histology. The remaining
      pea crabs were infected with an intranuclear bacilliform virus designated as P.
      pisum bacilliform virus (PpBV) in the hepatopancreatic epithelial cells,
      peritrichous ciliates on the gills, an intracytoplasmic microsporidian infection
      of the hepatopancreatocytes, a myophilic microsporidian infection, the gregarine
      Cephaloidophora fossor in the hepatopancreas, the entoniscid isopod Pinnotherion
      vermiforme, a low level nematode infection and an acanthocephalan cystacanth.
      Host reactions to infections were generally subdued. Results are discussed in
      relation to the endocommensal habitat of the pea crabs.

PMID- 22154879
TI  - Anopheles gambiae resistance to pyrethroid-treated nets in cotton versus rice
      areas in Mali.
AB  - The rise and spread of Anopheles gambiae s.l. (the major malaria vector sub
      Saharan Africa) resistance to pyrethroids is of great concern owing to the
      predominant role of pyrethroid-treated nets in the WHO global strategy for
      malaria control. Use of pyrethroids for agricultural purposes may exert a strong
      selection pressure, favouring the emergence of insecticide resistance. The
      objective of this study was to evaluate the efficacy of alpha-cypermethrin
      treated nets in settings where insecticides are used against pests. This was
      assessed in two ways, i.e. under laboratory conditions using the WHO standard
      cones test technique and in experimental huts, on Anopheles gambiae s.l.
      collected in two Malian rural sites, Koumantou characterised by cotton crops and
      high insecticide use and Selingue, a rice field area with low insecticide use.
      According to the WHO standard cones test technique, there was no difference
      between mosquitoes collected in the two sites; KD50 time was less than 3 min and
      the KD95 time below 30 min. Nevertheless, in the experimental huts with alpha
      cypermethrin treated bed nets, the mosquito mortality rate was significantly
      lower in Koumantou (102/361, 28.2%) than in Selingue (122/233, 52.3%) (RR: 0.65,
      95%CI: 0.56-0.76) (p<0.001). In addition, in Koumantou the percentage of unfed
      mosquitoes found in the veranda was much lower in the huts with untreated (26.0%,
      33/127) than in those with treated nets (92.2%, 118/128) (p<0.01) while in
      Selingue there was no difference between huts with treated and untreated bed
      nets. Alpha-cypermethrin treated bed nets had a significant effect on mortality
      and repelling behaviour of Anopheles gambiae s.l. though in Koumantou treated bed
      nets were less efficacious, possibly due to the intense use of pesticide for
      agriculture.

PMID- 22154880
TI  - Evidence for freedom from swine influenza in a remote area of Northern Vietnam.
AB  - Swine influenza is responsible for one of the most prevalent disease affecting
      the swine industry worldwide. Epidemiological surveys rarely focus on remote
      areas, because traditional farming systems characterized by locally consumed
      production and low pig densities are considered as having little influence on the
      emergence, re-emergence, persistence or spread of swine influenza viruses. In
      addition, routine disease investigations in remote areas are often neglected due
      to logistic and economical constraints. A bank of swine sera collected in 2005 in
      the ethnic minorities households of Ha Giang province (Northern Vietnam) located
      adjacent to the Chinese border was analyzed to estimate the seroprevalence of
      swine influenza (SI) and to identify potential risk factors for infection. The
      results suggest that this specific agro-ecological system is free from SI and is
      not favourable to SI spread either through pig-to-pig transmission, or through
      poultry-to-pig transmission.

PMID- 22154881
TI  - Distribution of phlebotomine sand flies (Diptera: Psychodidae) in Andorra: first
      finding of P. perniciosus and wide distribution of P. ariasi.
AB  - During July 2007 sand fly captures were carried out in Andorra using sticky
      castor oil traps set in sand fly resting places for four consecutive nights. The
      sampling stations were located between 800 and 2400 m above sea level. The
      specimens captured belong to two species of the genus Phlebotomus subgenus
      Larroussius, Phlebotomus ariasi and Phlebotomus perniciosus. The results shed new
      light on the wide geographical and altitudinal distribution of P. ariasi in
      Andorra, where it was located between 800 and 2200 m a.s.l. The study also
      identified P. perniciosus in Andorra for the first time, with captures below 1000
      m a.s.l. The finding of these species, both proven vectors of human and canine
      leishmaniasis in the bordering areas of France and Spain, is considered in terms
      of a possible emergence of leishmaniasis in Andorra, as has occurred in other
      parts of Europe.

PMID- 22154882
TI  - Colostrum from cattle immunized with a vaccine based on iron regulated proteins
      of Mannheimia haemolytica confers partial protection.
AB  - Passive protection afforded by colostrum from cattle vaccinated prepartum with an
      inactivated combination vaccine against viral pathogens and Mannheimia
      haemolytica (M. haemolytica) was evaluated against an experimental M. haemolytica
      challenge. Newborn calves were either fed colostrum from vaccinated dams or
      control colostrum. At approximately 3 weeks of age 24 calves were experimentally
      infected with M. haemolytica. Animals of both groups displayed clinical signs of
      respiratory disease and lung damage. The survival rate was considerably higher in
      calves which received colostrum from vaccinated cows. Colonies consistent with M.
      haemolytica were recovered in large numbers from all animals, but the geometric
      mean recovery was more than ten-times lower in the vaccinate colostrum fed
      animals. It can be concluded that maternal antibodies partly protected the calves
      against a severe M. haemolytica challenge.

PMID- 22154883
TI  - Value of PET scan in patients with retroperitoneal sarcoma treated with
      preoperative radiotherapy.
AB  - PURPOSE: Preoperative radiotherapy provides advantages in the management of
      retroperitoneal sarcoma (RPS). We describe our experience treating a cohort who
      underwent pre- and post-radiotherapy functional imaging with FDG-PET scan.
      METHODS AND MATERIALS: Consecutive patients presenting between January 1999 and
      December 2009 with a diagnosis of either primary or recurrent RPS were identified
      from the hospital patient record database using ICD codes, and cross-referenced
      with the completed radiotherapy course database. Those patients suitable for
      preoperative radiotherapy and surgery who underwent both pre- and post
      radiotherapy FDG-PET were included. Exclusions included presence of metastatic
      disease, age under 18 years and/or paediatric histology, and treatment with
      palliative intent. RESULTS: Eleven patients were included, of whom six were male.
      Median age was 63 years (range, 38-78 years). The majority of patients had Stage
      T2b, high-grade disease. Ten patients were treated at initial presentation and
      one at first local recurrence. A malignant diagnosis was confirmed in all
      patients who underwent CT-guided core biopsy; a diagnosis of sarcoma was reached
      in 91%. Sensitivity of FDG-PET imaging was 100%. Metabolic partial or complete
      response did not correlate with change in tumour size, nor pathological response
      assessment. Pulmonary and hepatic metastatic disease was detected in one patient
      on post-treatment imaging. All patients in the cohort completed preoperative
      radiotherapy. There was no grade 3 or 4 toxicity. Sixty-four percent proceeded to
      radical resection. Complete macroscopic excision was achieved in all cases. There
      was no perioperative mortality. CONCLUSION: Combined therapy with preoperative
      radiotherapy and surgery has acceptable levels of toxicity. CT-guided core biopsy
      is an accurate means of confirming a diagnosis of RPS prior to definitive
      treatment. Utility of PET scan in the management of RPS is evolving and further
      investigation is warranted.

PMID- 22154884
TI  - The impact of operative approach for oesophageal cancer on outcome: the
      transhiatal approach may influence circumferential margin involvement.
AB  - AIM: Surgery for oesophageal cancer remains the only means of cure for invasive
      tumours. It is claimed that the surgical approach for these cancers impacts on
      morbidity and may influence the ability to achieve tumour clearance and therefore
      survival, however there is no conclusive evidence to support one approach over
      another. This study aims to determine the impact of operative approach on tumour
      margin involvement and survival. METHODS: Data were extracted from the Scottish
      Audit of Gastric and Oesophageal Cancer (SAGOC), a prospective population-based
      audit of all oesophageal and gastric cancers in Scotland between 1997 and 1999
      with a minimum of five-year follow up. Analysis focused on the three commonest
      approaches (Ivor Lewis n = 140, transhiatal n = 68, left thoraco-laparotomy n =
      142) for oesophageal cancer. RESULTS: Operative approach had no significant
      impact on post-operative morbidity, mortality, overall margin involvement and
      survival. Transhiatal approach resulted in significantly more circumferential
      margin involvement (p = 0.019), and the presence of circumferential margin
      involvement significantly reduced five-year survival (median survival 13 months)
      compared to no margin involvement (median survival 25 months, p = 0.001).
      CONCLUSION: Surgical approach for oesophageal cancer had no significant effect on
      morbidity, post-operative mortality and five-year survival. Non-selective use of
      the transhiatal approach is associated with a significantly greater
      circumferential margin involvement, with positive circumferential margin
      impacting adversely on 5-year survival.

PMID- 22154885
TI  - Phase II trial of preoperative S-1 plus cisplatin followed by surgery for
      initially unresectable locally advanced gastric cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy and feasibility of
      preoperative chemotherapy with S-1 plus cisplatin in patients with initially
      unresectable locally advanced gastric cancer. METHODS: We enrolled patients with
      initially unresectable locally advanced gastric cancer because of severe lymph
      node metastases or invasion of adjacent structures. Preoperative chemotherapy
      consisted of S-1 at 80 mg/m(2) divided in two daily doses for 21 days and
      cisplatin at 60 mg/m(2) intravenously on day 8, repeated every 35 days. If a
      tumor decreased in size, patients received 1 or 2 more courses. Surgery involved
      radical resection with D2 lymphadenectomy. RESULTS: Between December 2000 and
      December 2007, 27 patients were enrolled on the study. No CR was obtained, but PR
      was seen in 17 cases, and the response rate was 63.0%. Thirteen patients (48.1%)
      had R0 resections. There were no treatment related deaths. The median overall
      survival time (MST) and the 3-year overall survival (OS) of all patients were
      31.4 months and 31.0%, respectively. Among the 13 patients who underwent curative
      resection, the median disease-free survival (DFS) and the 3-year DFS were 17.4
      months and 23.1%, respectively. The MST and the 3-year OS were 50.1 months and
      53.8%, respectively. The most common site of initial recurrence after the R0
      resection was the para-aortic lymph nodes. CONCLUSIONS: Preoperative S-1 plus
      cisplatin can be safely delivered to patients undergoing radical gastrectomy.
      This regimen is promising as neoadjuvant chemotherapy for resectable gastric
      cancer. For initially unresectable locally advanced gastric cancer, new trials
      using more effective regimens along with extended lymph node dissection are
      necessary.

PMID- 22154886
TI  - The distinctiveness of prolonged grief and posttraumatic stress disorder in
      adults bereaved by the attacks of September 11th.
AB  - BACKGROUND: Prolonged Grief Disorder (PGD) is a new diagnosis proposed for
      inclusion in the DSM-V. Although some studies have shown the distinctiveness of
      PGD and posttraumatic stress disorder (PTSD), this relationship has yet to be
      tested within a context of sudden, violent loss. METHOD: We conducted an
      exploratory factor analysis (EFA) using self-report data collected from a sample
      of 587 bereaved adults who lost friends and relatives in the attacks of September
      11th. Participants completed a 9-item PGD screening measure and the 17-item PTSD
      Checklist. RESULTS: A five factor solution representing two distinct constructs
      emerged from our analysis. Although two PGD items loaded onto factors containing
      PTSD symptoms, these items assessed non-specific symptomatology (i.e.,
      generalized negative affect). Thus, overall, our results support the
      distinctiveness of PGD and PTSD within a context of sudden, violent loss.
      LIMITATIONS: Data were collected using self-report. The representativeness of our
      sample is uncertain. CONCLUSIONS: These findings provide a stringent test of
      construct validity and suggest that PGD warrants inclusion in the diagnostic
      nosology. Adding PGD to the DSM-V will help clinicians better assess and treat
      psychopathology resulting from grief.

PMID- 22154887
TI  - Temperament and personality in bipolar II disorder.
AB  - BACKGROUND: There is limited research examining temperament and personality in
      bipolar II disorder. We sought to determine any over-represented temperament and
      personality features in bipolar II disorder compared to other affective groups.
      METHOD: Scores on a self-report measure of temperament and personality were
      examined in a sample of 443 participants diagnosed with unipolar, bipolar I and
      bipolar II disorder. RESULTS: After controlling for age, gender, age of
      depression onset and current depression severity, those with bipolar II disorder
      were characterized by higher irritability, anxious worrying, self-criticism and
      interpersonal sensitivity scores, and with lower social avoidance scores compared
      to unipolar participants. No differences were found between bipolar sub-types on
      any temperament and personality sub-scales. Limitations included the lack of a
      control group, a relatively small sample of bipolar I participants, and with the
      cross-sectional design disallowing conclusions regarding premorbid personality
      traits as opposed to illness 'scarring' effects. CONCLUSIONS: Further research
      should seek to clarify whether certain temperament and personality styles are
      over-represented in bipolar II disorder. Any over-represented characteristics may
      assist with diagnostic differentiation from phenomenologically similar conditions
      and lead to more appropriate clinical management.

PMID- 22154888
TI  - Deciphering the molecular genetic basis of NPC through functional approaches.
AB  - The identification of cancer genes in sporadic cancers has been recognized as a
      major challenge in the field. It is clear that deletion mapping, genomic
      sequencing, comparative genomic hybridization, or global gene expression
      profiling alone would not have easily identified candidate tumor suppressor genes
      (TSGs) from the huge array of lost regions or genes observed in nasopharyngeal
      carcinoma (NPC). In addition, the epigenetically silenced genes would not have
      been recognized by the mapping of deleted regions. In this review, we describe
      how functional approaches using monochromosome transfer may be used to circumvent
      the above problems and identify TSGs in NPC. A few examples of selected NPC TSGs
      and their functional roles are reviewed. They regulate a variety of gene
      functions including cell growth and proliferation, adhesion, migration, invasion,
      epithelial-mesenchymal transition, metastasis, and angiogenesis. These studies
      show the advantages of using functional approaches for identification of TSGs.

PMID- 22154889
TI  - Physical activity and nutrition among immigrant and refugee women: a community
      based participatory research approach.
AB  - BACKGROUND: Immigrant and refugee populations arrive to the U.S. healthier than
      the general population, but the longer they reside, the more they approximate the
      cardiovascular risk profiles of the country. Among women, these declines are
      partly mediated by less physical activity and lower dietary quality upon
      immigration. Given the complex forces that influence these behaviors, a community
      based participatory research (CBPR) approach is appropriate. Therefore, a
      socioculturally responsive physical activity and nutrition program was created
      with and for immigrant and refugee women in Rochester, Minnesota, through a CBPR
      approach. METHODS: Focus groups informed program content and revealed principles
      for designing the sessions. A 6-week program with two, 90-minute classes per week
      was conducted among 45 women (Hispanic, Somali, Cambodian, and non-immigrant
      African American). Average attendance was 22.5 women per class; 34 women
      completed the evaluation. RESULTS: Evaluation revealed high acceptability
      (average overall score of 4.85 out of 5 on the Physical Activity Class
      Satisfaction Questionnaire). After the intervention, participants were more
      likely to exercise regularly (p <= .001). They reported higher health-related
      quality of life (p <= .001) and self-efficacy for diet (p = .36) and exercise (p
      = .10). Likewise, there were trends for weight loss (87 vs 83.4 kg; p = .65),
      decreased waist circumference (99.6 vs 95.5 cm; p = .35), and lower blood
      pressure (125/80 vs 122/76 mm/Hg; p = .27). CONCLUSION: A CBPR approach to design
      and implement a socioculturally responsive fitness program was highly acceptable
      to immigrant and refugee women and demonstrated promising outcomes. Further
      testing of physical activity and nutrition interventions that arise organically
      from target communities are needed.

PMID- 22154890
TI  - A mystery caller evaluation of Medicaid staff responses about state coverage of
      abortion care.
AB  - OBJECTIVES: The Hyde Amendment prohibits federal Medicaid funding for abortion
      except when a woman is seeking an abortion for a pregnancy that is the result of
      rape or incest, or that threatens her life. We investigated how Medicaid staff in
      17 states responded to inquiries about coverage for abortion in the few
      circumstances that qualify for federal Medicaid funding. METHODS: Using a mystery
      caller approach, we surveyed Medicaid staff about the availability of abortion
      coverage, the process for obtaining coverage, and the associated costs for an
      abortion in circumstances of rape and life endangerment in five states where
      Medicaid coverage should be available to cover most abortions and in 12 states
      with restrictions on the circumstances under which Medicaid funding can be used
      for abortion. FINDINGS: We were able to complete 82% of surveys. Medicaid staff
      definitively provided information about the availability of coverage that was
      consistent with state policies in 64% of surveys. However, 52% of staff reported
      that coverage could be difficult to obtain and that rigorous documentation of the
      circumstances of the abortion was required. Information about copays for abortion
      was given in 78% of surveys. We subjectively rated the caller's experience with
      Medicaid staff as excellent during 32% of the surveys, adequate in 61% of
      surveys, and poor in 7% of surveys. CONCLUSION: Medicaid staff provided
      inconsistent information that was often discouraging of women seeking abortion
      coverage, suggesting that women may have difficulties obtaining accurate
      information about Medicaid coverage of abortion, which may deter access to care.

PMID- 22154892
TI  - Combining cellular automata and Lattice Boltzmann method to model multiscale
      avascular tumor growth coupled with nutrient diffusion and immune competition.
AB  - In the last decades the Lattice Boltzmann method (LB) has been successfully used
      to simulate a variety of processes. The LB model describes the microscopic
      processes occurring at the cellular level and the macroscopic processes occurring
      at the continuum level with a unique function, the probability distribution
      function. Recently, it has been tried to couple deterministic approaches with
      probabilistic cellular automata (probabilistic CA) methods with the aim to model
      temporal evolution of tumor growths and three dimensional spatial evolution,
      obtaining hybrid methodologies. Despite the good results attained by CA-PDE
      methods, there is one important issue which has not been completely solved: the
      intrinsic stochastic nature of the interactions at the interface between cellular
      (microscopic) and continuum (macroscopic) level. CA methods are able to cope with
      the stochastic phenomena because of their probabilistic nature, while PDE methods
      are fully deterministic. Even if the coupling is mathematically correct, there
      could be important statistical effects that could be missed by the PDE approach.
      For such a reason, to be able to develop and manage a model that takes into
      account all these three level of complexity (cellular, molecular and continuum),
      we believe that PDE should be replaced with a statistic and stochastic model
      based on the numerical discretization of the Boltzmann equation: The Lattice
      Boltzmann (LB) method. In this work we introduce a new hybrid method to simulate
      tumor growth and immune system, by applying Cellular Automata Lattice Boltzmann
      (CA-LB) approach.

PMID- 22154891
TI  - Structure-based design, synthesis and biological evaluation of N-pyrazole, N'
      thiazole urea inhibitors of MAP kinase p38alpha.
AB  - In this paper, we present the structure-based design, synthesis and biological
      activity of N-pyrazole, N'-thiazole-ureas as potent inhibitors of p38alpha
      mitogen-activated protein kinase (p38alpha MAPK). Guided by complex crystal
      structures, we employed the initially identified N-aryl, N'-thiazole urea
      scaffold and introduced key structural elements that allowed the formation of
      novel hydrogen bonding interactions within the allosteric site of p38alpha,
      resulting in potent type III inhibitors. [4-(3-tert-Butyl-5-{[(1,3-thiazol-2
      ylamino)carbonyl]amino}-1H-pyrazol-1-yl)-phenyl]acetic acid 18c was found to be
      the most potent compound within this series and inhibited p38alpha activity with
      an IC(50) of 135 +/- 21 nM. Its closest analog, ethyl [4-(3-tert-butyl-5-{[(1,3
      thiazol-2-ylamino)carbonyl]amino}-1H-pyrazol-1-yl)phenyl]acetate 18b, effectively
      inhibited p38alpha mediated phosphorylation of the mitogen activated protein
      kinase activated protein kinase 2 (MK2) in HeLa cells.

PMID- 22154893
TI  - Suppression of cardiac allograft vasculopathy in mice by inhibition of CC-motif
      chemokine receptor 5.
AB  - Cardiac allograft vasculopathy (CAV) is the leading cause of late morbidity and
      mortality in heart-transplant patients. Increasing evidences support the
      important role of chemokines and their receptors in transplant immunology.
      Chemokine-chemokine receptor interaction and subsequent recruitment of T
      lymphocytes to the graft are early events in the development of chronic rejection
      of transplanted hearts. In this study, we first inhibited CC-motif chemokine
      receptor 5 (CCR5) expression by using lentiviral-mediated gene transfer of an
      anti-CCR5 siRNA, which introduced through CD34(+) hematopoietic stem/progenitor
      cell transplantation. Stably marked lymphocytes expressing siRNA and consistent
      downregulation of CCR5 expression were detected. Our results showed that survival
      was significantly prolonged in CCR5 knock-down mice and donor hearts from siRNA
      treated mice developed markedly less CAV. Infiltration of CD4(+) and CD8(+) T
      lymphocytes into transplanted hearts was also markedly decreased. These findings
      suggest that CCR5 plays an important role in CAV development and inhibition of
      this chemokine could improve long-term survival after cardiac transplantation.

PMID- 22154894
TI  - [Cervical paraganglioma mimicking a thyroid nodule with recurrent nerve
      involvement].

PMID- 22154895
TI  - [Lupus, Graves' disease, and vasculitis: a case report].

PMID- 22154896
TI  - Understanding the central pharmacokinetics of spheroidal oral drug absorption
      system (SODAS) dexmethylphenidate: a positron emission tomography study of
      dopamine transporter receptor occupancy measured with C-11 altropane.
AB  - OBJECTIVE: Pediatric studies of the long-acting formulation (spheroidal oral drug
      absorption system [SODAS]) of the isomer dexmethylphenidate have shown a dose
      dependent efficacy through 12 hours. However, there are no studies of central
      nervous system (CNS) dopamine transporter occupancies. METHOD: Eighteen healthy
      volunteers underwent positron emission tomography (PET) imaging with C-11
      altropane before and after administration of oral doses of SODAS
      dexmethylphenidate. Each group of 6 subjects received 1 of 3 doses (20 mg, 30 mg,
      40 mg) before PET imaging at 1, 8, 10, 12 (20 mg and 30 mg), or 1, 8, 10, and 14
      (40 mg) hours after dosing. Transporter occupancy was calculated by standard
      methods. The study was conducted from January 2007 through December 2007.
      RESULTS: For all doses, plasma dexmethylphenidate levels and CNS dopamine
      transporter occupancies were greatest at 8 hours and decreased over time at 10,
      12, and 14 hours. Plasma dexmethylphenidate levels were correlated to dose (P <
      .003). Mean plasma levels were >= 6 ng/mL to at least 8 hours with 20 mg (5.7
      ng/mL), 10 hours with 30 mg, and 12 hours (extrapolated) with 40 mg. Dopamine
      transporter occupancies in the right caudate were 47% at 8 hours with 20 mg, 42%
      at hour 10 with 30 mg, and 46% (extrapolated) at hour 12 with 40 mg. Dopamine
      transporter occupancy was significantly correlated with plasma concentration of
      dexmethylphenidate (P < .001). CONCLUSIONS: These results confirm the study
      hypothesis that central dopamine transporter occupancy parallels peripheral
      pharmacokinetic findings in orally administered long-acting dexmethylphenidate in
      later hours after administration. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00593138.

PMID- 22154897
TI  - Emotional numbing in posttraumatic stress disorder: a functional magnetic
      resonance imaging study.
AB  - OBJECTIVE: To explore the functional neural correlates of emotional numbing
      symptoms in individuals with posttraumatic stress disorder (PTSD). METHOD: The
      study was conducted between September 2006 and June 2008 at the University of
      Western Ontario. Women with (n = 14) and without (n = 16) PTSD (based on DSM-IV
      criteria) completed a standardized emotional imagery task while undergoing
      functional magnetic resonance imaging, in addition to an assessment for emotional
      numbing symptoms. The study design was correlational, with primary outcome
      measures being blood oxygenation level-dependent (BOLD) response to emotional
      imagery task and self-reported severity of emotional numbing symptoms. Women
      without PTSD were not trauma exposed. RESULTS: In women with PTSD, emotional
      numbing symptoms predicted less positive affect in response to positive-valence
      scripts (P < .05) and less BOLD response within the dorsomedial prefrontal cortex
      during imagery of positive and negative scripts that were explicitly socially
      relevant (P < .001). In contrast, in women without PTSD, emotional numbing
      symptoms, while unrelated to subjective emotional responses, predicted greater
      response within the ventromedial prefrontal cortex during positive and negative
      scripts, in addition to scripts that elicited fear anxiety by nonsocial means
      (all P values < .001). The findings could not be attributed to dysphoria.
      CONCLUSIONS: These findings are consistent with previous research regarding
      emotional numbing and emotional awareness. Less response within the medial
      prefrontal cortex during emotional imagery in individuals with high emotional
      numbing may indicate deficient conscious and reflective emotional processing.
      Further study is required to elucidate associations between state and trait
      emotional numbing and the neural correlates of psychological treatments specific
      to emotional numbing.

PMID- 22154898
TI  - How informative are open-label studies for youth with bipolar disorder? A meta
      analysis comparing open-label versus randomized, placebo-controlled clinical
      trials.
AB  - OBJECTIVE: To examine the informativeness of open-label trials toward predicting
      results in subsequent randomized, placebo-controlled clinical trials of
      psychopharmacologic treatments for pediatric bipolar disorder. DATA SOURCES: We
      searched journal articles through PubMed at the National Library of Medicine
      using bipolar disorder, mania, pharmacotherapy, treatment and clinical trial as
      keywords. This search was supplemented with scientific presentations at national
      and international scientific meetings and submitted manuscripts from our group.
      STUDY SELECTION: Selection criteria included (1) enrollment of children diagnosed
      with DSM-IV bipolar disorder; (2) prospective assessment of at least 3 weeks; (3)
      monotherapy of a pharmacologic treatment for bipolar disorder; (4) use of a
      randomized placebo-controlled design or an open-label design for the same
      therapeutic compound; and (5) repeated use of the Young Mania Rating Scale (YMRS)
      as an outcome. DATA EXTRACTION: The following information and data were extracted
      from 14 studies: study design, name of medication, class of medication, dose of
      medication, sample size, age, sex, trial length, and YMRS mean and standard
      deviation baseline and follow-up scores. RESULTS: For both study designs, the
      pooled effect size was statistically significant (open-label studies, z = 8.88, P
      < .001; randomized placebo-controlled studies, z = 13.75, P < .001), indicating a
      reduction in the YMRS from baseline to endpoint in both study designs. In a meta
      analysis regression, study design was not a significant predictor of mean change
      in the YMRS. CONCLUSIONS: We found similarities in the treatment effects between
      open-label and randomized placebo-controlled studies in youth with bipolar
      disorder indicating that open-label studies are useful predictors of the
      potential safety and efficacy of a given compound in the treatment of pediatric
      bipolar disorder.

PMID- 22154899
TI  - Web-based assessment of depression in patients treated in clinical practice:
      reliability, validity, and patient acceptance.
AB  - OBJECTIVE: Calls for the use of standardized assessments in clinical practice
      have been increasing. A Web-based administration of outcome assessments offers
      several potential advantages over paper-and-pencil assessments, such as patient
      convenience, reduced missing data, reduced costs, automatic scoring, and
      generation of large databases. The present study from the Rhode Island Methods to
      Improve Diagnostic Assessments and Services (MIDAS) project evaluated the
      acceptability, reliability, and validity of a Web-based administration of a
      depression scale in patients receiving ongoing care for depression. METHOD: From
      June 2009 to July 2010, fifty-three depressed outpatients completed a Web-based
      and a paper version of the Clinically Useful Depression Outcome Scale (CUDOS).
      The vast majority of patients met DSM-IV criteria for either major depressive
      disorder (n = 36) or bipolar disorder (n = 9). Patients were also asked to
      complete a brief 6-question survey of the acceptability of the 2 modes of scale
      administration. At the time of the visit, the patients' psychiatrist completed
      the Montgomery-Asberg Depression Rating Scale (MADRS) and rated patients on the
      Clinical Global Impressions-Severity of Illness (CGI-S) scale and Global
      Assessment of Functioning (GAF). RESULTS: The correlation between the Web
      administered and paper versions of the CUDOS was high (P < .001). The mean scores
      were similar on the paper and Internet administrations. The internal consistency
      of the paper and Internet administrations of the CUDOS was high (both values,
      Cronbach alpha = .93), and all item-scale correlations for the paper and Internet
      versions were significant (median for paper administration = 0.76; median for
      Internet administration = 0.74). The paper and Internet versions of the CUDOS
      were equally correlated with clinicians' ratings on the MADRS, CGI-S, and GAF
      (all P values < .001). Patients reported high levels of satisfaction with
      Internet administration and preferred this method of monitoring outcome to paper
      administration in the office (all P values < .001). CONCLUSIONS: The results of
      this first study of the use of a Web-based system of monitoring outcome in
      routine clinical practice supported the reliability and validity of Internet
      administration of a depression scale, and patients clearly preferred Internet
      administration to completion of a paper-and-pencil questionnaire in the office.

PMID- 22154900
TI  - Trauma at the hands of another: longitudinal study of differences in the
      posttraumatic stress disorder symptom profile following interpersonal compared
      with noninterpersonal trauma.
AB  - OBJECTIVE: Survivors of traumatic events of an interpersonal nature typically
      have higher rates of posttraumatic stress disorder (PTSD) than survivors of
      noninterpersonal traumatic events. Little is known about potential differences in
      the nature or trajectory of PTSD symptoms in survivors of these different types
      of traumatic events. The current study aimed to identify the specific symptom
      profile of survivors of interpersonal and noninterpersonal trauma, and to examine
      changes in differences in the symptom profile over time. METHOD: The study
      examined PTSD symptom data from 715 traumatic injury survivors admitted to the
      hospital between April 2004 and February 2006, who were assessed 3, 12, and 24
      months after injury using the Clinician-Administered PTSD Scale (primary outcome
      measure). Multivariate analyses of variance were used to investigate differences
      in PTSD symptom profile over time between interpersonal and noninterpersonal
      trauma. RESULTS: Multivariate analyses of variance revealed significant
      differences between the 2 groups in overall severity of PTSD symptoms at each of
      the 3 time points: 3 months, F(17,696) = 5.86, P < .001; 12 months, F(17,696) =
      3.62, P < .001; 24 months, F(17,696) = 3.09, P < .001. Survivors of interpersonal
      trauma demonstrated significantly (P < .01) higher scores on 14 PTSD symptoms at
      3 months after injury but on only 6 symptoms by 24 months. Symptoms on which
      differences persisted were the PTSD unique symptoms more associated with fear and
      threat. CONCLUSIONS: Interpersonal trauma results in more severe PTSD symptoms in
      the early aftermath of trauma. Over the course of time, the distinctive
      persisting symptoms following interpersonal trauma involve fear-based symptoms,
      which suggest fear conditioning may be instrumental in persistent interpersonal
      PTSD.

PMID- 22154901
TI  - Mortality of neuroleptic malignant syndrome induced by typical and atypical
      antipsychotic drugs: a propensity-matched analysis from the Japanese Diagnosis
      Procedure Combination database.
AB  - OBJECTIVE: Neuroleptic malignant syndrome induced by atypical antipsychotics
      presents atypical clinical manifestations with fewer symptoms compared with
      neuroleptic malignant syndrome induced by typical antipsychotics. However, any
      differences in prognosis between these 2 types of drug-induced neuroleptic
      malignant syndrome remain unknown. We examined neuroleptic malignant syndrome
      related mortality in patients treated with typical or atypical antipsychotics by
      using a national administrative claims database. METHOD: Data of patients with a
      diagnosis of neuroleptic malignant syndrome between July and December in each of
      the 5 years from 2004 to 2008 were extracted from the Japanese Diagnosis
      Procedure Combination database. Data included patient background, use of
      antipsychotics, and in-hospital mortality. Propensity score matching was
      performed to formulate a balanced 1:1 matched study and to compare in-hospital
      mortality between neuroleptic malignant syndrome patients taking typical
      antipsychotics and those taking atypical antipsychotics. RESULTS: We identified
      423 neuroleptic malignant syndrome patients treated with typical antipsychotics
      and 215 neuroleptic malignant syndrome patients treated with atypical
      antipsychotics. Matching based on propensity scores produced 210 patients in each
      drug group. In-hospital mortality was substantially lower in the atypical
      antipsychotic group compared with the typical antipsychotic group, but the
      difference was not significant (3.3% vs 7.6%; OR = 0.44; 95% CI, 0.17-1.11; P =
      .084). CONCLUSIONS: The results show that neuroleptic malignant syndrome remains
      a life threatening disease among patients receiving antipsychotics. A tendency
      for lower mortality in the atypical antipsychotic group may reflect differences
      in the pathophysiology. However, to clarify whether there is a difference in
      neuroleptic malignant syndrome-related mortality with the 2 types of
      antipsychotics, further studies with larger samples are needed.

PMID- 22154902
TI  - Alpha-lipoic acid attenuates methionine choline deficient diet-induced
      steatohepatitis in C57BL/6 mice.
AB  - AIMS: Non-alcoholic steatohepatitis (NASH) is a liver disease that causes fat
      accumulation, inflammation and fibrosis. Increased oxidative stress contributes
      to hepatic inflammation and fibrosis by upregulation of Cytochrome P450 2E1
      (CYP2E1), endoplasmic reticulum (ER) stress and mitogen-activated protein kinase
      (MAPK) activity. This study examined whether alpha-lipoic acid (ALA), a naturally
      occurring thiol antioxidant, prevents steatohepatitis through the inhibition of
      several pathways involved in hepatic inflammation and fibrosis. MAIN METHODS:
      C57BL/6 mice were fed an MCD diet with or without ALA for 4weeks. Liver sections
      from mice on control or MCD diets with or without ALA were stained with
      hematoxylin-eosin, oil red O, and anti-4-HNE antibody. The effects of ALA on
      methionine-choline deficient MCD-diet induced plasma AST and ALT as well as
      tissue TBARS were measured. The effects of ALA on CYP2E1 expression, ER stress,
      MAPK levels, and NF-kappaB activity in MCD diet-fed mice liver were measured by
      northern and western blot analysis. KEY FINDINGS: Dietary supplementation with
      ALA reduced MCD diet-induced hepatic lipid accumulation, hepatic inflammation,
      TBARS, 4-HNE, and plasma ALT and AST levels. These effects were associated with a
      reduced expression of CYP2E1 and reduced ER stress and MAPK and NF-kappaB
      activity. SIGNIFICANCE: Taken together, the results of the present study indicate
      that ALA attenuates steatohepatitis through inhibition of several pathways, and
      provide the possibility that ALA can be used to prevent the development and
      progression of non-alcoholic fatty liver disease in patients who have strong risk
      factors for NASH.

PMID- 22154903
TI  - Comparative study of the cardioprotective effects of local and remote
      preconditioning in ischemia/reperfusion injury.
AB  - AIMS: Though the cardioprotective effects of local or remote preconditioning have
      been estimated, it is still unclear which of them is more reliable and provides
      more cardioprotection. The present investigation was directed to compare, in one
      study, the cardioprotective effects of different cycles of local or remote
      preconditioning in ischemia/reperfusion (I/R)-induced electrophysiological,
      biochemical and histological changes in rats. MAIN METHODS: Rats were randomly
      assigned into 10 groups. Groups 1 and 2 were normal and I/R groups, respectively.
      Other groups were subjected to 1, 2, 3, 4 cycles of local or remote
      preconditioning before myocardial I/R (40 min/10 min). Heart rate and ventricular
      arrhythmias were recorded during I/R progress. At the end of reperfusion, plasma
      creatine kinase-MB (CK-MB) activity and total nitrate/nitrite (NO(x)) were
      determined. In addition, lactate, adenine nucleotides, thiobarbituric acid
      reactive substances (TBARS), reduced glutathione (GSH) and myeloperoxidase (MPO)
      activity were estimated in the heart left ventricle. Histological examination was
      also performed to visualize the protective cellular effects of the effective
      cycle of local or remote preconditioning. KEY FINDINGS: In general, local
      preconditioning was more effective than remote preconditioning in reducing
      ventricular arrhythmias, CK-MB release, lactate accumulation and elevated MPO
      activity as well as preserving adenine nucleotides. Concerning the most effective
      group in each therapy, 3 cycles of local preconditioning provided more
      cardioprotection than that of remote preconditioning in the histological
      examination. SIGNIFICANCE: Despite being invasive, local preconditioning provided
      more effective cardioprotection than remote preconditioning in ameliorating the
      overall electrophysiological, biochemical and histological changes.

PMID- 22154904
TI  - Higher serum bone alkaline phosphatase as a predictor of mortality in male
      hemodialysis patients.
AB  - AIMS: Higher serum alkaline phosphatase predicts lower mortality in chronic
      kidney disease and hemodialysis patients without liver dysfunction because it
      reflects high bone turnover. The purpose of our study was to compare the
      significance of serum bone alkaline phosphatase (BAP) with that of other bone
      markers in prediction of all-cause mortality(ACM) in male hemodialysis patients.
      MAIN METHODS: The study was performed for 5 years. Serum BAP, intact osteocalcin
      (iOC), beta-CrossLaps (CTX), and intact parathyroid hormone (iPTH) were measured
      in 196 male hemodialysis patients without radiographic fracture. Their day-to-day
      variation during 5 consecutive days and diurnal variation were determined in 13
      healthy males. KEY FINDINGS: The patients were divided into higher and lower
      groups based on serum levels of bone markers(mean+/-SD: iPTH 218.6+/-214.5 pg/ml,
      BAP 23.6+/-12.2 U/L, iOC 42.8+/-45.2 ng/ml, CTX 1.71+/-1.23 nmol/L BCE). In
      Kaplan-Meier analysis, the higher BAP group had significantly higher ACM than the
      lower BAP group (P=0.013), whereas mortality did not differ between the higher
      and lower groups in other markers. Cox regression hazard analysis identified
      higher log BAP as a significant independent predictor [hazard ratio(HR)
      8.32(95%CI:1.18-58.98)] for ACM after adjustment for various factors including
      pre-existing cardiovasucular disease, presence of DM. The significant association
      of mortality with serum BAP alone, in contrast with other markers including CTX
      [HR0.64 (95%CI:0.16-2.47)], iOC [HR0.97(95%CI:0.36-2.64)], iPTH
      [HR0.84(95%CI:0.44-1.60)], it may be due to the narrower day-to-day variation and
      the absence of diurnal variation in serum BAP compared to other markers.
      SIGNIFICANCE: Higher serum BAP may be a predictor of ACM in male hemodialysis
      patients.

PMID- 22154905
TI  - An anxiolytic-like effect of hyperbaric oxygen in the mouse light/dark
      exploration test.
AB  - AIMS: We studied whether hyperbaric oxygen (HBO(2)) treatment, which is known to
      increase production of nitric oxide (NO) in the brain, might also produce an NO
      dependent anxiolytic-like behavioral response. MAIN METHODS: Male NIH Swiss mice
      (20-25g) were subjected to a 60-min HBO(2) treatment at different absolute
      atmospheres, and anxiety was assessed using the light/dark exploration test at
      different time intervals following the cessation of HBO(2) treatment. To
      ascertain the underlying mechanism of action, other groups of mice were
      pretreated with the NO synthase inhibitor N(G)-monomethyl-l-arginine acetate, the
      NO scavenger 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1
      oxy-3-oxide (carboxy-PTIO), the soluble guanylyl cyclase-inhibitor 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or the benzodiazepine antagonist
      flumazenil to determine their influence on the HBO(2)-induced anxiolytic-like
      effect. KEY FINDINGS: A 60-min HBO(2) treatment at 3.0 absolute atmospheres
      increased the time spent by mice in the light compartment that lasted up to 90
      min following the end of HBO(2) treatment. This anxiolytic effect of HBO(2) was
      significantly reduced by pretreatment with L-NMMA, carboxy-PTIO, ODQ and
      flumazenil. SIGNIFICANCE: Based on these findings, we conclude that a 60-min
      HBO(2) treatment is capable of inducing an anxiolytic effect that possibly
      involves NO, cyclic GMP and the benzodiazepine binding site.

PMID- 22154906
TI  - Effects of globin digest and its active ingredient Trp-Thr-Gln-Arg on
      galactosamine/lipopolysaccharide-induced liver injury in ICR mice.
AB  - AIMS: We investigated the effects of globin digest (GD) and its active ingredient
      Trp-Thr-Gln-Arg (WTQR) on galactosamine/lipopolysaccharide (GalN/LPS)-induced
      liver injury in imprinting control region (ICR) mice. MAIN METHODS: The effects
      of WTQR and GD on the liver injury were examined by measuring the survival rate,
      serum aminotransferase activities, hepatic components, antioxidant enzyme
      activities, histopathological analysis, serum levels and hepatic gene expression
      of tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2
      (MIP-2), and nitric oxide (NO) or inducible nitric oxide synthase (iNOS), and
      nuclear factor-kappa B (NF-kappaB) p65 content in GalN/LPS-treated ICR mice.
      RAW264 mouse macrophages were used to confirm the anti-inflammatory effects of
      WTQR and GD on the macrophages. KEY FINDINGS: WTQR and GD increased the survival
      rate, suppressed the serum aminotransferase activities, serum levels and hepatic
      gene expression of TNF-alpha, MIP-2, and NO or iNOS, and nuclear NF-kappaB p65
      content in GalN/LPS-treated mice; decreased the oxidized glutathione content,
      increased the superoxide dismutase activity, and decreased the histopathological
      grade values of the hepatocyte necrosis and lobular inflammation in GalN/LPS
      injured liver; and suppressed the release levels and gene expression of TNF
      alpha, MIP-2, and NO or iNOS, and nuclear NF-kappaB p65 content in LPS-stimulated
      RAW264 macrophages. WTQR and GD may improve the antioxidant defense system and
      inflammatory status in GalN/LPS-injured liver. SIGNIFICANCE: These findings
      indicate that WTQR and GD have hepatoprotective effects on GalN/LPS-induced liver
      injury in ICR mice.

PMID- 22154907
TI  - Cardioprotection requires flipping the 'posttranslational modification' switch.
AB  - Minimizing damage during reperfusion of the heart following an ischemic event is
      an important part of the recovery process, as is preventing future recurrences;
      however, restoring blood perfusion to the heart following ischemia can lead to
      apoptosis, necrosis, and finally, diminished cardiac function. Exercise reduces
      risk of heart disease and has been shown to improve the recovery of the heart
      following ischemia and reperfusion. Brief intermittent ischemic events
      administered prior to or following a myocardial infarction have also been
      demonstrated to reduce the infarct size and improve cardiac function, thereby
      providing cardioprotection. Many signaling transduction pathways are known to
      regulate cardioprotection, including but not limited to calcium regulation,
      antioxidant scavenging, and kinase activation. Although posttranslational
      modifications (PTM) such as phosphorylation, O-GlcNAcylation, methylation, and
      acetylation are essential regulators of these pathways, their contributions are
      often overlooked in the literature. This review will examine how PTMS are
      important regulators of cardioprotection and demonstrate why they should be
      targeted when developing future therapies for the minimization of damage caused
      by cardiac ischemia and reperfusion.

PMID- 22154908
TI  - Decreased expression of small-conductance Ca2+-activated K+ channels SK1 and SK2
      in human chronic atrial fibrillation.
AB  - AIMS: Small-conductance Ca2+-activated K+ (SK) channels are recognized as new ion
      channel candidates in atrial fibrillation (AF), with pivotal implications as
      novel drug targets due to their atrial-selective distribution in humans. The
      purpose of this study was to investigate whether SK channels and the Ca2+
      activated K+ current (IK,Ca) are involved in electrical remodeling of human
      chronic AF (cAF) and whether they display the differential distribution between
      the right (RA) and left atria (LA). MAIN METHODS: The right (RAA) and left atrial
      appendage (LAA) myocytes were obtained from 29 sinus rhythm (SR) and 22 cAF
      patients. The IK,Ca and action potential (AP) were recorded using the patch-clamp
      technique. Three SK channel subtypes (SK1-3) expressions were assayed by western
      blot and real-time quantitative PCR analysis. KEY FINDINGS: The IK,Ca was
      decreased and its role in AP repolarization was attenuated in cAF, concomitant
      with a significant decrease in protein and mRNA levels of SK1 and SK2. In either
      SR or cAF, there was no difference in the IK,Ca density and protein and mRNA
      expression levels of SK1-3 between RAA and LAA myocytes. SIGNIFICANCE: Our
      results demonstrated that SK1 and SK2 are involved in electrical remodeling of
      cAF. SK1-3 and IK,Ca do not display the inter-atrial differential distribution in
      SR or cAF. These findings provide a new insight into mechanisms of electrical
      remodeling of human cAF.

PMID- 22154909
TI  - Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down
      regulation of CD38.
AB  - AIMS: Sleep apnea syndrome (SAS) is characterized by recurrent episodes of oxygen
      desaturation during sleep, the development of daytime sleepiness, and
      deterioration in the quality of life. Accumulating evidence suggests the
      association of intermittent hypoxia (IH), a hallmark of SAS, and type 2 diabetes
      independently on body mass index and waist circumference. In addition to insulin
      resistance, the progression to type 2 diabetes is dependent on the impairment of
      glucose-induced insulin secretion (GIS) from pancreatic beta-cells. However, the
      direct effects of IH on GIS are elusive. MAIN METHODS: HIT-T15 hamster beta-cells
      and isolated rat islets were exposed to 64 cycles/24 h of IH (5 min hypoxia/10
      min normoxia) or normoxia for 24 h. Changes of GIS and gene expression in IH
      treated beta-cells were analyzed by ELISA and real-time RT-PCR, respectively. KEY
      FINDINGS: After IH treatment, GIS both from IH-treated HIT-T15 cells and isolated
      rat islets were significantly attenuated. The level of insulin mRNA was unchanged
      by IH. The mRNA levels of glucose transporter 2 (Glut2), glucokinase (GK),
      sulfonylurea receptor1 (SUR1), and L-type Ca2+channel1.2 (Cav1.2) in IH-treated
      islets were similar to those in normoxia-treated islets. In contrast, the mRNA
      level of CD38 in IH-treated islets was significantly lower than that in normoxia
      treated islets. The reporter gene assay revealed that the transcription of CD38
      was attenuated by IH, and the transfection of CD38 expression vector recovered
      the attenuation of GIS by IH. SIGNIFICANCE: These results indicate that IH stress
      directly attenuates GIS from beta-cells via the down-regulation of CD38.

PMID- 22154910
TI  - The synthesis, structure, optical and photocatalytic properties of silica-coated
      cadmium sulfide nanocomposites of different shapes.
AB  - The CdS nanostructure undergoes photochemical dissolution, and hence, the
      photocatalytic activity deteriorates with light irradiation time. A thin layer of
      silica coating over CdS surface may prevent the photocorrosion and coalescence of
      quantum size CdS particles. Hence, we synthesized SiO(2)@CdS nanocomposites of
      different shapes and characterized them by XRD, HRTEM, EDX, SAED, BET surface
      area measurement and absorption and emission study. The dispersion of spherical
      CdS (Cd-2.62 at% and S-2.33 at%) nanoparticles of cubic crystal structure into
      thick amorphous SiO(2) (43.79 at%) matrix is demonstrated here. The fabrication
      of core (CdS)-shell (SiO(2)) structure (SiO(2)@CdS) consisting of CdS nanorod (Cd
      19.79 at% and S-22.90 at%) core (length ~126 nm and width ~6 nm) having
      characteristic lattice fringes of hexagonal crystals and thin SiO(2) (12.81 at%)
      shell (thickness=1-1.4 nm) is successfully achieved for the first time. The
      surface area (21.2m(2)/g) of CdS nanorod (aspect ratio=21) is found to increase
      (42.3m(2)/g) after SiO(2) coating. The photoluminescence of CdS nanosphere (485
      nm) and nanorod (501 nm) is highly quenched after SiO(2) layer formation. The
      superior photocatalytic activity of SiO(2)@CdS composites for the benzaldehyde
      oxidation under UV irradiation has been displayed.

PMID- 22154911
TI  - Cyclodextrin induced switch between heterolytic and homolytic dediazoniation
      mechanisms.
AB  - We have investigated the kinetics and mechanism of dediazoniation of 4
      nitrobenzenediazonium (4NBD) tetrafluoroborate in the presence of alpha
      cyclodextrin, alpha-CD, and gamma-cyclodextrin, gamma-CD, under acidic (HCl,
      pH=2) conditions by employing a combination of spectrometric and chromatographic
      techniques. In the absence of CDs, dediazoniation follows first-order kinetics,
      with t(1/2)=22,000 s at T=60  degrees C, but addition of small amounts of either
      alpha-CD or gamma-CD leads to more rapid but not first-order kinetics with
      t(1/2)~400 s when [alpha-CD]=20 [4NBD] or [gamma-CD]=15 [4NBD]. Analyses of
      reaction mixtures by HPLC indicate that three main dediazoniation products are
      formed depending on the particular experimental conditions. These are 4
      nitrophenol, ArOH, nitrobenzene, ArH, and 4-nitrochlorobenzene, ArCl. In the
      absence of CDs, the main dediazoniation product is the substitution product ArOH,
      but on increasing the concentration of CD, the reduction product ArH becomes
      predominant at the expense of ArOH, indicating that a switch between the
      heterolytic and homolytic reaction mechanisms take place under acidic conditions,
      where little significant ionization of the OH groups of the CDs takes place
      (pK(a)~12). Addition of the surfactant sodium dodecylsulfate, SDS, blocks the CD
      cavity inhibiting 4NBD dediazoniation and decreasing the yields of ArH with a
      concomitant increase in that of ArOH, suggesting that 4NBD ions form an inclusion
      complex prior to reacting with the OH groups of the CDs. This O-coupling reaction
      leads to the formation of a highly unstable Z-diazo ether adduct that cannot
      isomerize to the much more stable E-isomer because of the geometric restrictions
      imposed by the CD cavity, splitting homolitically.

PMID- 22154912
TI  - Use of X-ray absorption near edge structure (XANES) to identify physisorption and
      chemisorption of phosphate onto ferrihydrite-modified diatomite.
AB  - This paper presents a novel technique integrating bulk-sensitive and surface
      sensitive XANES methods to distinguish between physisorption and chemisorption
      for phosphate adsorption onto ferrihydrite-modified diatomite (FHMD). XANES P K
      edge, L-edge, and Fe M-edge spectra were obtained for reference samples
      (K(2)HPO(4) and FePO(4).2H(2)O) and test samples (phosphate adsorbed onto FHMD
      (FHMD-Ps) and Si-containing ferrihydrite (FHYD-Ps)). A resolvable pre-edge peak
      in the P K-edge spectra of FHMD-Ps and FHYD-Ps provided direct evidence for the
      formation of P-O-Fe(III) coordination and the occurrence of chemisorption. The
      resemblance between the P L-edge spectra of K(2)HPO(4) and FHMD-Ps and the marked
      difference between the spectra of FHMD-Ps and FePO(4).2H(2)O indicated the intact
      existence of the adsorbate and the adsorbent. The similarity between Fe M-edge
      spectra of FHMD and FHMD-Ps and the difference between the spectra of FHMD-Ps and
      FePO(4).2H(2)O confirmed the findings from P L-edge analyses. Therefore,
      chemisorption and physisorption coexisted during phosphate adsorption onto FHMD.
      Phosphate chemisorption occurred in the deeper zone of FHMD (from 50 nm to 5
      MUm); whereas physisorption occurred in the zone of FHMD shallower than 50 nm
      since the probing depth of XANES P K-edge method is 5 MUm and that of P L-edge
      and Fe M-edge methods is 50 nm.

PMID- 22154913
TI  - Surface properties of amino-functionalized poly(epsilon-caprolactone) membranes
      and the improvement of human mesenchymal stem cell behavior.
AB  - In this study, a series of membranes with different amino group densities were
      prepared to investigate the surface properties of the novel poly(gamma-amino
      epsilon-caprolactone-co-epsilon-caprolactone) (NPCL) copolymer synthesized by our
      laboratory. Meanwhile, the human mesenchymal stem cells' (hMSCs) behavior on
      those membranes was examined. The molecular characteristics of the NPCL
      copolymers were characterized by nuclear magnetic resonance (NMR), size exclusion
      chromatography (SEC), and differential scanning calorimetry (DSC). Surface
      properties of membranes were characterized by water contact angle analysis, X-ray
      photoelectron spectroscopy analysis (XPS), and atomic force microscopy (AFM). It
      was found that the incorporation of amino groups to the poly(epsilon
      caprolactone) (PCL) backbone resulted in an augmented wettability, a decreased
      crystallinity, and also an increased surface roughness on the NPCL membranes. In
      vitro cell experiments showed a significant enhancement in hMSCs' adhesion,
      proliferation, and osteogenic differentiation on NPCL membranes compared with
      virgin PCL membrane, and demonstrated that surface properties of membrane played
      an important role in tailoring cell behavior.

PMID- 22154914
TI  - Vanadium oxide intercalated with polyelectrolytes: novel layered hybrids with
      anion exchange properties.
AB  - Novel anion exchange hybrid materials were developed by the insertion of
      poly(diallymethylammonium chloride) (PDDACl) and poly(allylamine hydrochloride)
      (PAHCl) polyelectrolytes into V(2)O(5) interlayer spaces using hydrothermal
      treatment and were used to host an anionic cyanine dye. A systematic study of the
      hybrid material synthesis by direct in situ reaction of PDDACl and PAHCl
      polycations with V(2)O(5) powders showed that the interlayer space of V(2)O(5)
      expands from 0.44 nm to 1.40 nm and 1.80 nm upon intercalation of PDDACl and
      PAHCl polyelectrolytes, respectively. X-ray photoelectron spectroscopy and DR UV
      Vis-NIR spectroscopy revealed that some V(5+) sites were reduced to V(4+) during
      the intercalation of the polyelectrolytes, these acted as both charge balancing
      entities for the negative oxide sheets and carriers for exchange sites located in
      the V(2)O(5) interlayer space. The interlayer separation is consistent with the
      existence of coiled conformation of the polycations. The hybrid materials
      produced [PDDACl](0.24)[PDDA](0.29)V(2)O(5) and [PAHCl](0.28)[PAH](0.47)V(2)O(5),
      exhibited approximately 45.0% and 37.0% of chloride ions still available for
      anionic exchange, respectively. These materials were used to encapsulate a
      cyanine anionic dye. The presence of the dye was evidenced in the
      [PDDACl](0.24)[PDDA](0.29)V(2)O(5) by significant fluorescence, with emission
      peak centered at 617 nm.

PMID- 22154915
TI  - Toxicological assessment of tridecafluorohexylethyl methacrylate (6:2 FTMAC).
AB  - The toxicity of tridecafluorohexylethyl methacrylate (6:2 FTMAC), an acrylic
      monomer used in producing polymeric substances, was evaluated. 6:2 FTMAC has low
      acute oral and dermal toxicity (LD50>5000 mg/kg), was not a skin or eye irritant,
      and did not demonstrate skin sensitization potential in a local lymph node assay
      (LLNA). 6:2 FTMAC was not mutagenic in the bacterial reverse mutation (Ames) test
      or in the mouse lymphoma assay. 6:2 FTMAC induced structural aberrations in human
      peripheral blood lymphocytes in vitro in the absence of metabolic activation but
      not in the presence of S9 metabolic activation. No numerical aberrations were
      detected under any testing condition. Also, no increase occurred in structural or
      numerical chromosomal aberrations in an in vivo mouse micronucleus assay in 6:2
      FTMAC treated animals compared to controls. 6:2 FTMAC was administered at 0, 100,
      500 and 1000 mg/kg/day via gavage to male and female SD rats for 14 days. No test
      substance-related effects on mortality, clinical signs, body weights, nutritional
      parameters, or clinical pathology were observed at any dose. Test substance
      related increases in liver weights in males and females at all dose levels and
      thyroid and kidney weights in 500 and 1000 mg/kg/day males were noted. While
      there was no histopathological correlate for thyroid and kidney weight changes,
      minimal hypertrophy was noted in liver in males and females at 1000 mg/kg/day
      group. The changes noted in teeth (altered mineralization; retention of
      basophilic material) and femur (increased mineralization) in all treated groups
      were not associated with clinical signs or microscopic changes and were likely
      related to free fluoride formed from 6:2 FTMAC metabolism. Plasma (3-4-fold) and
      urine (30-50-fold) fluoride was higher in treated groups versus controls.
      Therefore, the changes noted in organ weights, teeth, femur, plasma or urine were
      not considered adverse. In the repeated dose toxicity study, the no-observed
      adverse-effect-level (NOAEL) was 1000 mg/kg/day. Based on mean measured
      concentrations, the 96-h LC50 in fathead minnow was >14.5 mg/L and the 72-h EC50
      in Pseudokirchneriella subcapitata was >24.6 mg/L, while the 48-h EC50 in Daphnia
      magna, based on nominal concentrations, was >120 mg/L. Overall, 6:2 FTMAC is
      considered to have low toxicity potential based on these studies.

PMID- 22154917
TI  - Glucagon-like peptide-1 inhibits insulinotropic effects of oxyntomodulin and
      glucagon in cattle.
AB  - Oxyntomodulin (OXM), glucagon, and glucagon-like peptide-1 (GLP-1), peptide
      hormones derived from the glucagon gene, play an important role in glucose
      homeostasis. The insulinotropic action of these three homologous peptides has
      been well documented in monogastric animals. However, information on the
      relationships among these peptides in insulin-releasing action, specifically in
      ruminants, is still insufficient. In this regard, we carried out two experiments
      in cattle. In experiment 1, effects of glucagon and GLP-1 on plasma insulin and
      glucose were investigated in 10-mo-old Holstein steers (347 +/- 8 kg, n = 8)
      under normoglycemic conditions. Peptides were administered intravenously at dose
      rates of 0.12, 0.25, 0.50, and 1.25 nmol/kg body weight (BW). In experiment 2,
      the relationships among OXM, glucagon, and GLP-1 in the insulinotropic and
      glucoregulatory actions were elucidated in 3-mo-old Holstein steers (94 +/- 2 kg,
      n = 8) using agonist-antagonist strategy. In agonist strategy, these three
      peptides were administered alone or coadministered at dose rates of 10 MUg of
      OXM/kg BW, 4 MUg of glucagon/kg BW, and 2 MUg of GLP-1/kg BW. In antagonist
      strategy, 2 MUg of each peptide was administered alone or in combination with 10
      MUg of [des His1, des Phe6, Glu9] glucagon amide (a glucagon receptor antagonist)
      or exendin-4 (5-39) amide (a GLP-1 receptor antagonist). Our results showed that
      OXM, glucagon, and GLP-1 had insulinotropic actions in ruminants under
      normoglycemic conditions. Our results also showed that the insulin-releasing
      effects of OXM and glucagon were mediated through both GLP-1 receptors (GLP-1R)
      and glucagon receptors. These insulinotropic effects of OXM and glucagon through
      GLP-1R were inhibited by GLP-1. Our findings expand the relationships among OXM,
      glucagon, and GLP-1 in the insulinotropic and glucoregulatory actions.

PMID- 22154916
TI  - The inhibitory effect of manganese on acetylcholinesterase activity enhances
      oxidative stress and neuroinflammation in the rat brain.
AB  - BACKGROUND: Manganese (Mn) is a naturally occurring element and an essential
      nutrient for humans and animals. However, exposure to high levels of Mn may cause
      neurotoxic effects. The pathological mechanisms associated with Mn neurotoxicity
      are poorly understood, but several reports have established it is mediated, at
      least in part, by oxidative stress. OBJECTIVES: The present study was undertaken
      to test the hypothesis that a decrease in acetylcholinesterase (AChE) activity
      mediates Mn-induced neurotoxicity. METHODS: Groups of 6 rats received 4 or 8
      intraperitoneal (i.p.) injections of 25mg MnCl(2)/kg/day, every 48 h. Twenty-four
      hours after the last injection, brain AChE activity and the levels of F(2)
      isoprostanes (F(2)-IsoPs) and F(4)-neuroprostanes (F(4)-NPs) (biomarkers of
      oxidative stress), as well as prostaglandin E(2) (PGE(2)) (biomarker of
      neuroinflammation) were analyzed. RESULTS: The results showed that after either 4
      or 8 Mn doses, brain AChE activity was significantly decreased (p<0.05), to 60 +/
      16% and 55 +/- 13% of control levels, respectively. Both treated groups
      exhibited clear signs of neurobehavioral toxicity, characterized by a significant
      (p<0.001) decrease in ambulation and rearings in open-field. Furthermore, Mn
      treatment caused a significant increase (p<0.05) in brain F(2)-IsoPs and PGE(2)
      levels, but only after 8 doses. In rats treated with 4 Mn doses, a significant
      increase (p<0.05) in brain F(4)-NPs levels was found. To evaluate cellular
      responses to oxidative stress, we assessed brain nuclear factor-erythroid 2 p45
      related factor 2 (Nrf2) and Mn-superoxide dismutase (Mn-SOD, SOD2) protein
      expression levels. A significant increase in Mn-SOD protein expression (p<0.05)
      and a trend towards increased Nrf2 protein expression was noted in rat brains
      after 4 Mn doses vs. the control group, but the expression of these proteins was
      decreased after 8 Mn doses. Taken together, these results suggest that the
      inhibitory effect of Mn on AChE activity promotes increased levels of neuronal
      oxidative stress and neuroinflammatory biomarkers.

PMID- 22154919
TI  - Impact of pain on the course of depressive and anxiety disorders.
AB  - The combination of pain and depression or anxiety is commonly seen in clinical
      practice. Little is known about the influence of pain on psychopathology over
      time, as previous studies have been mainly cross-sectional. The objectives of
      this study are to determine the impact of pain on the course of depressive and/or
      anxiety disorders, and investigate to what extent the association between pain
      and course of these mental disorders is mediated by psychiatric characteristics.
      Data from the Netherlands Study of Depression and Anxiety (NESDA), collected
      between 2004 and 2009, were used. A total of 1209 participants with a depressive
      and/or anxiety disorder at baseline were followed up for 2 years. Baseline pain
      was assessed by location, duration, use of pain medication, and severity (based
      on Chronic Pain Grade). Course of depressive and anxiety disorders was assessed
      by Composite International Diagnostic Interview (CIDI) and Life Chart Interview.
      A higher number of pain locations (OR=1.10; P=.008), joint pain (OR=1.64;
      P<.001), >= 90 days of pain (OR=1.40; P=.009), daily use of pain medication
      (OR=1.57; P=.047), and a higher Chronic Pain Grade score (OR=1.27; P<.001) were
      associated with worse course of depressive and anxiety disorders. These
      associations were largely mediated by baseline severity of the mental disorder.
      However, joint pain remained associated with a worse course independent of
      baseline psychiatric characteristics. This study shows that patients with pain
      are more prone to a chronic course of depressive and anxiety disorders. More
      attention to pain seems to be necessary when diagnosing and treating these
      disorders. Future research should focus on treatment modalities for this co
      occurrence, with joint pain in particular.

PMID- 22154920
TI  - Unmyelinated and myelinated skin nerve damage in Guillain-Barre syndrome:
      correlation with pain and recovery.
AB  - We performed a prospective study in 32 patients with Guillain-Barre syndrome
      (GBS) or its variants to correlate intraepidermal nerve fiber density (IENFD) at
      the distal leg and lumbar region with pain, autonomic dysfunction, and outcome.
      In the acute phase, IENFD was reduced in 60% and 61.9% of patients at the distal
      leg and lumbar region, respectively. In the acute phase, 43.7% of patients
      complained of neuropathic pain. Their IENFD at the distal leg was significantly
      lower than in patients without pain (P<.001) and correlated with pain intensity
      (r(s)=-0.51; P=.003). Intriguingly, also patients with the pure motor variant of
      GBS and pain had low IENFD. At 6-month follow-up, only 3 patients complained of
      persisting neuropathic pain, whereas 3 patients reported late-onset pain
      symptoms. IENFD in the acute phase did not predict presence or intensity of pain
      at 6-month follow-up. IENFD in the acute phase did not correlate with clinical
      dysautonomia or GBS severity at nadir. However, it correlated with poorer GBS
      disability score at 6 months (P=.04), GBS score at nadir (P=.03), and clinically
      probable dysautonomia (P=.004). At 6-month follow-up, median IENFD remained
      significantly low both at the distal leg (P=.024) and lumbar region (P=.005).
      Double and triple staining confocal microscope studies showed diffuse damage of
      myelinated dermal nerves along with axonal degeneration, and mononuclear cell
      infiltration. Unmyelinated and myelinated skin nerves are diffusely affected in
      GBS and its variants, including the pure motor form. IENFD declines early,
      remains low over time, correlates with pain severity in the acute phase, and may
      predict long-term disability.

PMID- 22154918
TI  - Plasma components affect accuracy of circulating cancer-related microRNA
      quantitation.
AB  - Circulating microRNAs (miRNAs) have emerged as candidate biomarkers of various
      diseases and conditions including malignancy and pregnancy. This approach
      requires sensitive and accurate quantitation of miRNA concentrations in body
      fluids. Herein we report that enzyme-based miRNA quantitation, which is currently
      the mainstream approach for identifying differences in miRNA abundance among
      samples, is skewed by endogenous serum factors that co-purify with miRNAs and
      anticoagulant agents used during collection. Of importance, different miRNAs were
      affected to varying extent among patient samples. By developing measures to
      overcome these interfering activities, we increased the accuracy, and improved
      the sensitivity of miRNA detection up to 30-fold. Overall, the present study
      outlines key factors that prevent accurate miRNA quantitation in body fluids and
      provides approaches that enable faithful quantitation of miRNA abundance in body
      fluids.

PMID- 22154921
TI  - Sensory signs in complex regional pain syndrome and peripheral nerve injury.
AB  - This study determined patterns of sensory signs in complex regional pain syndrome
      (CRPS) type I and II and peripheral nerve injury (PNI). Patients with upper-limb
      CRPS-I (n=298), CRPS-II (n=46), and PNI (n=72) were examined with quantitative
      sensory testing according to the protocol of the German Research Network on
      Neuropathic Pain. The majority of patients (66%-69%) exhibited a combination of
      sensory loss and gain. Patients with CRPS-I had more sensory gain (heat and
      pressure pain) and less sensory loss than patients with PNI (thermal and
      mechanical detection, hypoalgesia to heat or pinprick). CRPS-II patients shared
      features of CRPS-I and PNI. CRPS-I and CRPS-II had almost identical somatosensory
      profiles, with the exception of a stronger loss of mechanical detection in CRPS
      II. In CRPS-I and -II, cold hyperalgesia/allodynia (28%-31%) and dynamic
      mechanical allodynia (24%-28%) were less frequent than heat or pressure
      hyperalgesia (36%-44%, 67%-73%), and mechanical hypoesthesia (31%-55%) was more
      frequent than thermal hypoesthesia (30%-44%). About 82% of PNI patients had at
      least one type of sensory gain. QST demonstrates more sensory loss in CRPS-I than
      hitherto considered, suggesting either minimal nerve injury or central
      inhibition. Sensory profiles suggest that CRPS-I and CRPS-II may represent one
      disease continuum. However, in contrast to recent suggestions, small fiber
      deficits were less frequent than large fiber deficits. Sensory gain is highly
      prevalent in PNI, indicating a better similarity of animal models to human
      patients than previously thought. These sensory profiles should help prioritize
      approaches for translation between animal and human research.

PMID- 22154922
TI  - Emerging role of microglial kinin B1 receptor in diabetic pain neuropathy.
AB  - Nowadays diabetes mellitus has reached epidemic level and is considered as the
      primary cause of foot amputation and pain neuropathy. The classical theories
      explaining the development of diabetic pain neuropathy include the imbalance of
      neuronal biochemical pathways (Polyol pathway, Na(+)/K(+) ATPase pump, AGE, ROS)
      and microangiopathy which promote nerve fibers depolarization, sensitization,
      ectopic discharges, demyelization and ultimately neuronal death. However, the
      current pharmacotherapy targeting those pathways brings variable, not always
      satisfactory and temporal relief in patients experiencing diabetic pain
      neuropathy. Interestingly, recent research in animal models yielded compelling
      evidence that glial cells, mainly microglia, play a critical role in the
      mediation of diabetic pain facilitation mechanisms. Preventing microglia
      activation could therefore be considered as a potential therapeutic target. The
      lack of specific agents inhibiting microglia activity remains, however, a major
      obstacle for further treatment in diabetic patients. An alternative and new
      strategy would be the targeting of key mediators involved in microglia
      activation, migration and the subsequent release of pro-inflammatory substances
      contributing to neuronal hyperexitability. The present review summarizes recent
      evidence that the kinin B1 receptor (B1R) may represent such a target of
      potential value for new medicines in the treatment of chronic pain. A few
      selective B1R antagonists have been fully characterized in animal models although
      small molecules orally active are urgently needed for targeting human B1R on CNS
      microglia. Thus far, the pharmacological blockade of kinin B1R in various animal
      paradigms or its genetic deletion in B1R knock-out mice failed to cause unwanted
      side effects, making this approach feasible. This is consistent with the highly
      inducible feature of this atypical G-protein coupled receptor whose expression
      can be seen as the alarming signature of immune and inflammatory diseases,
      notably diabetes mellitus.

PMID- 22154923
TI  - Down-regulation of beta-carotene hydroxylase increases beta-carotene and total
      carotenoids enhancing salt stress tolerance in transgenic cultured cells of
      sweetpotato.
AB  - Sweetpotato (Ipomoea batatas Lam.) is an important industrial crop and source of
      food that contains useful components, including antioxidants such as carotenoids.
      beta-Carotene hydroxylase (CHY-beta) is a key regulatory enzyme in the beta-beta
      branch of carotenoid biosynthesis and it catalyzes hydroxylation into both beta
      carotene to beta-cryptoxanthin and beta-cryptoxanthin to zeaxanthin. To increase
      the beta-carotene content of sweetpotato through the inhibition of further
      hydroxylation of beta-carotene, the effects of silencing CHY-beta in the
      carotenoid biosynthetic pathway were evaluated. A partial cDNA encoding CHY-beta
      was cloned from the storage roots of orange-fleshed sweetpotato (cv. Shinhwangmi)
      to generate an RNA interference-IbCHY-beta construct. This construct was
      introduced into cultured cells of white-fleshed sweetpotato (cv. Yulmi). Reverse
      transcription-polymerase chain reaction analysis confirmed the successful
      suppression of IbCHY-beta gene expression in transgenic cultured cells. The
      expression level of phytoene synthase and lycopene beta-cyclase increased,
      whereas the expression of other genes showed no detectable change. Down
      regulation of IbCHY-beta gene expression changed the composition and levels of
      carotenoids between non-transgenic (NT) and transgenic cells. In transgenic line
      #7, the total carotenoid content reached a maximum of 117 MUg/g dry weight, of
      which beta-carotene measured 34.43 MUg/g dry weight. In addition, IbCHY-beta
      silenced calli showed elevated beta-cryptoxanthin and zeaxanthin contents as well
      as high transcript level P450 gene. The 2,2-diphenyl-1-picrylhydrazyl radical
      scavenging activity (DPPH) in transgenic cells was more than twice that in NT
      cells. RNA-IbCHY-beta calli increased abscisic acid (ABA) content, which was
      accompanied by enhanced tolerance to salt stress. In addition, the production of
      reactive oxygen species measured by 3,3'-diaminobenzidine (DAB) staining was
      significantly decreased in transgenic cultured cells under salt stress. Taken
      together, the present results indicate that down-regulation of IbCHY-beta
      increased beta-carotene contents and total carotenoids in transgenic plant cells
      and enhanced their antioxidant capacity.

PMID- 22154924
TI  - [The surrogate for inpatients].
AB  - The French legal framework of the surrogate has been defined by a law passed in
      2002 concerning the patients' rights, in response to the absence of prior rights
      of the incompetent patient. The surrogate is designated only by a competent major
      patient. In the case of competent patient, the surrogate may support the patient
      throughout the course of care, including during the hospitalizations or
      consultations. In the case of incompetent patient, the surrogate must be involved
      in the decision-making process. A poor designation and a lack of the surrogate's
      involvement emerge from different French studies since 2002, especially in the
      end-of-life decisions, despite a specific law passed in 2005, which reinforced
      the surrogate's role in this context. The evolution of the patients' rights, in
      France as in most of the industrialized countries, should lead to specific
      actions to improve the surrogate's involvement, in the respect of the ethical
      principles of autonomy, beneficence and non-maleficence.

PMID- 22154925
TI  - [Individualized treatment of hepatitis C virus infection].
AB  - The current treatment of chronic hepatitis C since several years, the association
      of pegylated interferon and ribavirine, allows to obtain a virological
      eradication in around 55% of patients, including 45% of those infected with the
      genotype 1. The cure, defined by an undetectable viremia 24 weeks after the
      discontinuation of treatment, is associated to an improvement of the prognosis of
      the patients with a decrease of mortality and morbidity. If the virologic
      recovery allows fibrosis regression, including cirrhosis reversal, why not to
      treat every HCV-infected patient? Because first therapy is not mandatory in all
      the patients (minim liver disease, co-morbidities which may be contraindications
      to therapy), second adverse events are frequent and may be severe, third costs
      are high (the antiviral treatment but also hematological growth factors...) and
      finally the treated patients do not recover constantly. This has resulted in
      personalized therapies based on the severity of the disease, the early viral
      kinetics, pharmacologic monitoring, genetic and immunological factors. In
      addition to these factors of personalization, the development of new anti-viral C
      molecules, the protease inhibitors (boceprevir or telaprevir which are about to
      be approved in combination with pegylated interferon and ribavirine) will allow
      to achieve a sustained virologic response in around 75% of cases.

PMID- 22154926
TI  - [An inguinal dirofilariosis mimicking a groin hernia].

PMID- 22154927
TI  - [IgG4 related disease].
AB  - IgG4 related disease (IgG4 RD) was first reported as autoimmune pancreatitis then
      it was established as a systemic disorder characterised by high blood level of
      IgG4 and fibrosis with rich plasmocytes IgG4+ in almost all organs. IgG4 RD is
      very sensitive to corticosteroid therapy. IgG4 RD has a high prevalence in
      eastern countries. Numerous articles on this topic are published and new
      diagnostic criteria are regularly established. The autoimmune or allergic
      mechanism of IgG4 RD is still a matter of debate. Interestingly, IgG4 subclass of
      antibody has anti-inflammatory features. IgG4 RD is not yet very well
      characterised in western countries. Whether IgG4 is involved in IgG4 RD,
      pathophysiology is to be defined. IgG4 RD spontaneously regresses in some cases
      so indications of treatment are not already well clear.

PMID- 22154928
TI  - [Letter on the article: "Snus"].

PMID- 22154929
TI  - [Gastroparesis: pathophysiology and management].
AB  - The prevalence of gastroparesis is increasing. Diabetes mellitus and sequelae of
      oesogastric surgery are the two main causes of gastroparesis. In some patients,
      gastroparesis seems a postinfectious disease after its sudden onset after a viral
      infection. In about one third of the patients, gastroparesis is considered as
      idiopathic. In diabetic patients, gastroparesis impairs glycaemic control. Due to
      the low positive predictive value of symptoms, a gastric emptying study is often
      necessary to confirm a suspected diagnosis of gastroparesis. The symptomatic
      efficacy of erythromycin is higher than that of other prokinetics. This efficacy
      is higher when erythromycin is given intravenously. Hyperglycaemia impairs this
      symptomatic effect. Due to a tachyphylaxis phenomenon, the clinical effect of
      erythromycin decreases with the duration of treatment. In refractory gastroperis,
      either duodenal or jejunal enteral feeding, or high-frequency gastric electrical
      stimulation are possible therapeutic options while endoscopic alternatives
      (intrapyloric botulinum injection or pyloric balloon dilation) give
      unsatisfactory results.

PMID- 22154931
TI  - Local drug delivery strategies for cancer treatment: gels, nanoparticles,
      polymeric films, rods, and wafers.
AB  - Polymer-based drug delivery depots have been investigated over the last several
      decades as a means to improve upon the lack of tumor targeting and severe
      systemic morbidities associated with intravenous chemotherapy treatments. These
      localized therapies exist in a variety of form factors designed to facilitate the
      delivery of drug directly to the site of disease in a controlled manner, sparing
      off-target tissue toxicities. Many of these depots are biodegradable and designed
      to maintain therapeutic concentrations of drug at the tumor site for a prolonged
      period of time. Thus a single implantation procedure is required, sometimes
      coincident with tumor excision surgery, and thereby biodegrading following
      complete release of the loaded active agent. Even though localized polymer depot
      delivery systems have been investigated, a surprisingly small subset of these
      technologies has demonstrated potentially curative preclinical results for cancer
      applications, and fewer have progressed toward commercialization. The aims of
      this article are to review the most well-studied and efficacious local polymer
      delivery systems from the last two decades, to examine the rationale for
      utilizing drug-eluting polymer implants in cancer patients, and to identify the
      patient cohorts that could most benefit from localized therapy. Finally, a
      discussion of the physiological barriers to localized therapy (i.e. drug
      penetration, transport), technical hurdles, and future outlook of the field is
      presented.

PMID- 22154930
TI  - Influence of cAMP and protein kinase A on neurite length from spiral ganglion
      neurons.
AB  - Regrowth of peripheral spiral ganglion neuron (SGN) fibers is a primary objective
      in efforts to improve cochlear implant outcomes and to potentially reinnervate
      regenerated hair cells. Cyclic adenosine monophosphate (cAMP) regulates neurite
      growth and guidance via activation of protein kinase A (PKA) and Exchange Protein
      directly Activated by Cylic AMP (Epac). Here we explored the effects of cAMP
      signaling on SGN neurite length in vitro. We find that the cAMP analog, cpt-cAMP,
      exerts a biphasic effect on neurite length; increasing length at lower
      concentrations and reducing length at higher concentrations. This biphasic
      response occurs in cultures plated on laminin, fibronectin, or tenascin C
      suggesting that it is not substrate dependent. cpt-cAMP also reduces SGN neurite
      branching. The Epac-specific agonist, 8-pCPT-2'-O-Me-cAMP, does not alter SGN
      neurite length. Constitutively active PKA isoforms strongly inhibit SGN neurite
      length similar to higher levels of cAMP. Chronic membrane depolarization
      activates PKA in SGNs and also inhibits SGN neurite length. However, inhibition
      of PKA fails to rescue neurite length in depolarized cultures implying that
      activation of PKA is not necessary for the inhibition of SGN neurite length by
      chronic depolarization. Expression of constitutively active phosphatidylinositol
      3-kinase, but not c-Jun N-terminal kinase, isoforms partially rescues SGN neurite
      length in the presence of activated PKA. Taken together, these results suggest
      that activation of cAMP/PKA represents a potential strategy to enhance SGN fiber
      elongation following deafness; however such therapies will likely require careful
      titration so as to promote rather than inhibit nerve fiber regeneration.

PMID- 22154932
TI  - Quantitative structure-property relationship modeling of remote liposome loading
      of drugs.
AB  - Remote loading of liposomes by trans-membrane gradients is used to achieve
      therapeutically efficacious intra-liposome concentrations of drugs. We have
      developed Quantitative Structure Property Relationship (QSPR) models of remote
      liposome loading for a data set including 60 drugs studied in 366 loading
      experiments internally or elsewhere. Both experimental conditions and computed
      chemical descriptors were employed as independent variables to predict the
      initial drug/lipid ratio (D/L) required to achieve high loading efficiency. Both
      binary (to distinguish high vs. low initial D/L) and continuous (to predict real
      D/L values) models were generated using advanced machine learning approaches and
      5-fold external validation. The external prediction accuracy for binary models
      was as high as 91-96%; for continuous models the mean coefficient R(2) for
      regression between predicted versus observed values was 0.76-0.79. We conclude
      that QSPR models can be used to identify candidate drugs expected to have high
      remote loading capacity while simultaneously optimizing the design of formulation
      experiments.

PMID- 22154933
TI  - An injectable depot system for sustained intraperitoneal chemotherapy of ovarian
      cancer results in favorable drug distribution at the whole body, peritoneal and
      intratumoral levels.
AB  - The current study characterizes the impact of docetaxel (DTX) distribution on
      efficacy following sustained intraperitoneal (IP) chemotherapy in murine models
      of ovarian cancer. A polymer-lipid biodegradable depot (PoLigel) was used to
      deliver DTX in a sustained manner over 21-days following IP administration.
      Distribution and efficacy studies were carried out in SCID mice bearing SKOV3 IP
      solid tumors or C57BL/6 mice with ID8 IP ascites fluid. In addition, a
      subcutaneous (SC) SKOV3 model was used to determine whether systemic drug levels
      that result from IP administration of the PoLigel influence antitumor efficacy.
      Immunostained IP and SC SKOV3 tumor sections were used to study cell death,
      intratumoral drug distribution and tumor penetration. Sustained concentrations of
      DTX were observed in plasma, tissue, tumor and ascites over the entire study
      period. Drug accumulation was several fold greater in tumors and ascites when
      compared to plasma levels. Sustained chemotherapy resulted in significant
      reduction in tumor burden and ascites volume. IP tumors showed greater cell death
      compared to the SC tumors as seen by higher TUNEL and caspase-3 expression. At
      the intratumoral level, DTX distributed more towards the core of IP tumors
      compared to the SC tumors. Tumor penetration of drug from nearest blood vessel
      was 1.5 fold greater in the IP tumors than the SC tumors. Overall, favorable drug
      distribution at the whole-body, peritoneal and intratumoral levels in combination
      with local and systemic sustained drug exposure contribute to the high efficacy
      observed. These results encourage the clinical use of IP sustained chemotherapy
      for ovarian cancer.

PMID- 22154934
TI  - Refeeding hypophosphataemia in malnutrition patients: prevention and treatment.

PMID- 22154935
TI  - Chop (Ddit3) is essential for D469del-COMP retention and cell death in
      chondrocytes in an inducible transgenic mouse model of pseudoachondroplasia.
AB  - Cartilage oligomeric matrix protein (COMP), a secreted glycoprotein synthesized
      by chondrocytes, regulates proliferation and type II collagen assembly. Mutations
      in the COMP gene cause pseudoachondroplasia and multiple epiphyseal dysplasia.
      Previously, we have shown that expression of D469del-COMP in transgenic mice
      causes intracellular retention of D469del-COMP, thereby recapitulating
      pseudoachondroplasia chondrocyte pathology. This inducible transgenic D469del
      COMP mouse is the only in vivo model to replicate the critical cellular and
      clinical features of pseudoachondroplasia. Here, we report developmental studies
      of D469del-COMP-induced chondrocyte pathology from the prenatal period to
      adolescence. D469del-COMP retention was limited prenatally and did not negatively
      affect the growth plate until 3 weeks after birth. Results of immunostaining,
      transcriptome analysis, and qRT-PCR suggest a molecular model in which D469del
      COMP triggers apoptosis during the first postnatal week. By 3 weeks (when most
      chondrocytes are retaining D469del-COMP), inflammation, oxidative stress, and DNA
      damage contribute to chondrocyte cell death by necroptosis. Importantly, by
      crossing the D469del-COMP mouse onto a Chop null background (Ddit3 null), thereby
      eliminating Chop, the unfolded protein response was disrupted, thus alleviating
      both D469del-COMP intracellular retention and premature chondrocyte cell death.
      Chop therefore plays a significant role in processes that mediate D469del-COMP
      retention. Taken together, these results suggest that there may be an optimal
      window before the induction of significant D469del-COMP retention during which
      endoplasmic reticulum stress could be targeted.

PMID- 22154936
TI  - D469del-COMP retention in chondrocytes stimulates caspase-independent
      necroptosis.
AB  - Mutations in the cartilage oligomeric matrix protein gene (COMP) cause
      pseudoachondroplasia (PSACH). This dysplasia results from the intracellular
      retention of mutant COMP protein and premature death of growth-plate
      chondrocytes. Toward better understanding of these underlying mechanisms, we
      examined D469del-COMP activation of the unfolded protein response and cell death
      pathways in rat chondrosarcoma cells. Using an inducible expression system, we
      examined the effects of D469del-COMP retention after 4 days of mRNA expression
      and then 5 days without inducing agent. Retention of D469del-COMP stimulated Chop
      (Ddit3) and Gadd34 (Ppp1r15a) and triggered reactivation of protein translation
      that exacerbated intracellular retention. High levels of Nox4 and endoplasmic
      reticulum receptor stress-inducible Ero1beta generated reactive oxygen species,
      causing oxidative stress. Increased expression of Gadd genes and presence of
      gammaH2AX indicated that DNA damage was occurring. The presence of cleaved
      apoptosis inducing factor (tAIF) and the absence of activated caspases indicated
      that retention of D469del-COMP triggers cell death in chondrocytes by
      necroptosis, a caspase-independent programmed necrosis. Loss of growth-plate
      chondrocytes by necroptosis was also found in our pseudoachondroplasia mouse
      model. These results suggest a model in which D469del-COMP expression induces
      persistent endoplasmic reticulum stress, oxidative stress, and DNA damage, thus
      priming chondrocytes for necroptosis. We define for the first time the precise
      mechanisms underlying D469del-COMP pathology in pseudoachondroplasia and suggest
      that oxidative stress and AIF may be promising therapeutic targets.

PMID- 22154937
TI  - Human DNA polymerase eta is pre-aligned for dNTP binding and catalysis.
AB  - Pre-steady-state kinetic studies on Y-family DNA polymerase eta (Poleta) have
      suggested that the polymerase undergoes a rate-limiting conformational change
      step before the phosphoryl transfer of the incoming nucleotide to the primer
      terminus. However, the nature of this rate-limiting conformational change step
      has been unclear, due in part to the lack of structural information on the Poleta
      binary complex. We present here for the first time a crystal structure of human
      Poleta (hPoleta) in binary complex with its DNA substrate. We show that the
      hPoleta domains move only slightly on dNTP binding and that the polymerase by and
      large is pre-aligned for dNTP binding and catalysis. We also show that there is
      no major reorientation of the DNA from a nonproductive to a productive
      configuration and that the active site is devoid of metals in the absence of
      dNTP. Together, these observations lead us to suggest that the rate-limiting
      conformational change step in the Poleta replication cycle likely corresponds to
      a rate-limiting entry of catalytic metals in the active site.

PMID- 22154938
TI  - A reverse binding motif that contributes to specific protease inhibition by
      antibodies.
AB  - The type II transmembrane serine protease family consists of 18 closely related
      serine proteases that are implicated in multiple functions. To identify
      selective, inhibitory antibodies against one particular type II transmembrane
      serine protease, matriptase [MT-SP1 (membrane-type serine protease 1)], a phage
      display library was created with a natural repertoire of Fabs [fragment antigen
      binding (Fab)] from human naive B cells. Fab A11 was identified with a 720 pM
      inhibition constant and high specificity for matriptase over other trypsin-fold
      serine proteases. A Trichoderma reesei system expressed A11 with a yield of ~200
      mg/L. The crystal structure of A11 in complex with matriptase has been determined
      and compared to the crystal structure of another antibody inhibitor (S4) in
      complex with matriptase. Previously discovered from a synthetic single-chain
      variable fragment library, S4 is also a highly selective and potent matriptase
      inhibitor. The crystal structures of the A11/matriptase and S4/matriptase
      complexes were solved to 2.1 A and 1.5 A, respectively. Although these
      antibodies, discovered from separate libraries, interact differently with the
      protease surface loops for their specificity, the structures reveal a similar
      novel mechanism of protease inhibition. Through the insertion of the H3 variable
      loop in a reverse orientation at the substrate-binding pocket, these antibodies
      bury a large surface area for potent inhibition and avoid proteolytic
      inactivation. This discovery highlights the critical role that the antibody
      scaffold plays in positioning loops to bind and inhibit protease function in a
      highly selective manner. Additionally, Fab A11 is a fully human antibody that
      specifically inhibits matriptase over other closely related proteases, suggesting
      that this approach could be useful for clinical applications.

PMID- 22154939
TI  - Inhibition of Pseudomonas aeruginosa virulence: characterization of the AprA-AprI
      interface and species selectivity.
AB  - Pseudomonas aeruginosa secretes the virulence factor alkaline protease (AprA) to
      enhance its survival. AprA cleaves one of the key microbial recognition
      molecules, monomeric flagellin, and thereby diminishes Toll-like receptor 5
      activation. In addition, AprA degrades host proteins such as complement proteins
      and cytokines. P. aeruginosa encodes a highly potent inhibitor of alkaline
      protease (AprI) that is solely located in the periplasm where it is presumed to
      protect periplasmic proteins against secreted AprA. We set out to study the
      enzyme-inhibitor interactions in more detail in order to provide a basis for
      future drug development. Structural and mutational studies reveal that the
      conserved N-terminal residues of AprI occupy the protease active site and are
      essential for inhibitory activity. We constructed peptides mimicking the N
      terminus of AprI; however, these were incapable of inhibiting AprA-mediated
      flagellin cleavage. Furthermore, we expressed and purified AprI of P. aeruginosa
      and the homologous (37% sequence identity) AprI of Pseudomonas syringae, which
      remarkably show species specificity for their cognate protease. Exchange of the
      first five N-terminal residues between AprI of P. syringae and P. aeruginosa did
      not affect the observed specificity, whereas exchange of only six residues
      located at the AprI surface that contacts the protease did abolish specificity.
      These findings are elementary steps toward the design of molecules derived from
      the natural inhibitor of the virulence factor AprA and their use in therapeutic
      applications in Pseudomonas and other Gram-negative infections.

PMID- 22154940
TI  - Industrial biotechnology - past, present and future.

PMID- 22154941
TI  - Potential impact and cost-effectiveness of multi-biofortified rice in China.
AB  - Biofortification, that is, improving the micronutrient content of staple foods
      through crop breeding, could be a pro-poor, pro-rural, agriculture-based
      intervention to reduce the health burden of micronutrient malnutrition. While the
      potential cost-effectiveness of crops biofortified with single micronutrients was
      shown in previous research, poor people often suffer from multiple micronutrient
      deficiencies, which should be accounted for in biofortification initiatives. This
      study is the first to estimate the potential health benefits and cost
      effectiveness of multi-biofortification. Rice with enhanced provitamin A, zinc,
      iron and folate concentrations is used as a concrete example. The research is
      conducted for China, the largest rice producer in the world, where micronutrient
      malnutrition remains a major public health problem. Using the DALY (disability
      adjusted life year) framework, the current annual health burden of the four
      micronutrient deficiencies in China is estimated at 10.6 million DALYs.
      Introducing multi-biofortified rice could lower this burden by up to 46%. Given
      the large positive health impact and low recurrent costs of multi
      biofortification, this intervention could be very cost effective: under
      optimistic assumptions, the cost per DALY saved would be around US$ 2; it would
      stay below US$ 10 even under pessimistic assumptions.

PMID- 22154942
TI  - Mandibular distraction in the setting of chromosome 4q deletion.
AB  - Deletions of the long arm of chromosome 4 (4q) are rare, with an estimated
      incidence of roughly 1 in 10,000 live births. Patients present with a
      constellation of findings, including cardiac malformations, micrognathia in the
      setting of Pierre Robin sequence, microcephaly, genitourinary anomalies, short
      stature, anomalies of the small fingers of the hand, moderate or severe learning
      disability, and/or severe psychomotor retardation(2-4) The dysmorphic features
      include hypertelorism, a broad nasal bridge, with a short nose and anteverted
      nares, a long philtrum, a thin upper lip, and micrognathia. The cardiopulmonary
      complications, including asphyxia and apnea contribute significantly to morbidity
      and mortality. The authors describe a patient with 4q deletion syndrome and
      respiratory difficulty, secondary to Robin sequence. They report the successful
      use of distraction osteogenesis to address the associated micrognathia and tongue
      displacement and avoid long-term tracheostomy.

PMID- 22154943
TI  - Biased excitable networks: how cells direct motion in response to gradients.
AB  - The actin cytoskeleton in motile cells has many of the hallmarks of an excitable
      medium, including the presence of propagating waves. This excitable behavior can
      account for the spontaneous migration of cells. A number of reports have
      suggested that the chemoattractant-mediated signaling can bias excitability, thus
      providing a means by which cell motility can be directed. In this review, we
      discuss some of these observations and theories proposed to explain them. We also
      suggest a mechanism for cell polarity that can be incorporated into the existing
      framework.

PMID- 22154945
TI  - Female genital tract immunity: distinct immunological challenges for vaccine
      development.
AB  - The population explosion and unintended pregnancies, sexually transmitted
      diseases including human immunodeficiency virus, and cervical cancer, are major
      challenges to health worldwide. Their prevention might be achieved through
      vaccination-based approaches to activate specific immunity against pathogen- or
      fertility-associated antigens in the female genital tract (FGT). This article
      aims to review methodologies for enhancing adaptive immunity in the FGT to
      maximize the response to vaccination. Most components of the adaptive and innate
      mucosal immune system are present in the FGT and several features are common with
      the nasopharynx/bronchial and gastrointestinal tracts. In contrast to other
      mucosal sites, the FGT has minimal local lymphoid tissue. Other sites primarily
      produce IgA and IgM while in the FGT, especially the vaginocervix, IgG is the
      predominant immunoglobulin secreted. In rodents, data exist to substantiate a
      common mucosal immune system interconnecting the nasal/bronchial,
      gastrointestinal, and female genital tracts. The intranasal route seems the most
      efficacious to induce an immunity in the FGT especially when combined with a
      systemic or parenteral route. In humans, for induction of secretory IgA and IgG
      antibodies in the FGT, immunization by the nasal or the vaginal route is
      effective. In vaginal immunization, a strong and consistent antibody response is
      best achieved following vaccination during the follicular phase of the menstrual
      cycle. Antibodies administered systemically percolate into the FGT and can
      provide immunoprotection against target molecules or cells. Thus, as well as
      active immunization using selected routes, the passive immunization approach may
      provide a viable alternative to vaccinology for future development.

PMID- 22154944
TI  - Structural organization of the kinetochore-microtubule interface.
AB  - Successful mitosis depends on the stable, yet regulated attachment of chromosomes
      to spindle microtubules. The kinetochore, a large macromolecular structure
      assembled at sites of centromeric heterochromatin, is responsible for generating
      and regulating these essential attachments. Over the last several years,
      concerted experimental efforts have brought the structural view of the
      kinetochore-microtubule interface more clearly into focus. Here, we review
      important recent advancements and discuss several unresolved questions regarding
      how kinetochores dynamically bridge mitotic chromosomes to spindle microtubules.

PMID- 22154946
TI  - Feedforward non-Michaelis-Menten mechanism for CO(2) uptake by Rubisco:
      contribution of carbonic anhydrases and photorespiration to optimization of
      photosynthetic carbon assimilation.
AB  - Rubisco, the most abundant protein serving as the primary engine generating
      organic biomass on Earth, is characterized by a low catalytic constant (in higher
      plants approx. 3s(-1)) and low specificity for CO(2) leading to photorespiration.
      We analyze here why this enzyme evolved as the main carbon fixation engine. The
      high concentration of Rubisco exceeding the concentration of its substrate CO(2)
      by 2-3 orders of magnitude makes application of Michaelis-Menten kinetics invalid
      and requires alternative kinetic approaches to describe photosynthetic CO(2)
      assimilation. Efficient operation of Rubisco is supported by a strong flux of
      CO(2) to the chloroplast stroma provided by fast equilibration of bicarbonate and
      CO(2) and forwarding the latter to Rubisco reaction centers. The main part of
      this feedforward mechanism is a thylakoidal carbonic anhydrase associated with
      photosystem II and pumping CO(2) from the thylakoid lumen in coordination with
      the rate of electron transport, water splitting and proton gradient across the
      thylakoid membrane. This steady flux of CO(2) limits photosynthesis at saturating
      CO(2) concentrations. At low ambient CO(2) and correspondingly limited capacity
      of the bicarbonate pool in the stroma, its depletion at the sites of Rubisco is
      relieved by utilizing O(2) instead of CO(2), i.e. by photorespiration, a process
      which supplies CO(2) back to Rubisco and buffers the redox state and energy level
      in the chloroplast. Thus, the regulation of Rubisco function aims to keep steady
      non-equilibrium levels of CO(2), NADPH/NADP and ATP/ADP in the chloroplast stroma
      and to optimize the condition of homeostatic photosynthetic flux of matter and
      energy.

PMID- 22154947
TI  - Selective attention to fearful faces during pregnancy.
AB  - BACKGROUND: There is some evidence that pregnancy may be associated with
      cognitive affective changes, including increased ability to encode emotional
      faces signaling threat and increased anxiety. Nevertheless, findings to date are
      inconsistent, and there are few data on correlations with endocrine and hormonal
      measures. The aim of this study was to investigate danger sensitivity, as
      measured by selective attention to fearful and angry faces during pregnancy, and
      to correlate findings with distress and anxiety levels, glucocorticoid (cortisol)
      and gonadal hormones (estrogen, progesterone and testosterone). METHODS:
      Selective attention to fearful, angry and happy faces was assessed in pregnant
      women (n=44) and non-pregnant controls (n=25) using a modified version of an
      emotional Stroop task. General distress was assessed using the K-10, and state
      and trait anxiety using the Spielberger State-Trait Inventory. Levels of
      cortisol, estrogen, progesterone and testosterone were determined at trimester 2
      and 3. Analyses of variance, regression and correlational analyses were used to
      investigate associations between variables. RESULTS: Pregnant women showed
      altered attentional responses to fearful faces, in comparison to controls. When
      analyzed according to different levels of distress (K-10>20 or K-10<=20),
      distressed pregnant women had significantly increased selective attention to
      fearful faces compared to distressed non-pregnant controls. Attention to fear was
      significantly associated with increased levels of estrogen and progesterone at
      trimester 2, and decreased levels of cortisol at trimester 3 of pregnancy.
      CONCLUSION: Heightened sensitivity to danger cues during pregnancy is consistent
      with a perspective that emphasizes the importance of parental precaution and the
      adaptive significance of responding to potentially hazardous stimuli during this
      period. Such changes may be particularly apparent in distressed women, and may be
      mediated by changes in glucocorticoid and gonadal hormone systems during
      pregnancy.

PMID- 22154948
TI  - Severe acute autoimmune hepatitis after natalizumab treatment.

PMID- 22154949
TI  - Colon capsule endoscopy may represent an effective tool for colorectal cancer
      screening: a single-centre series.

PMID- 22154950
TI  - Inverse correlation between plasma oxysterol and LDL-cholesterol levels in
      hepatitis C virus-infected patients.
AB  - BACKGROUND: Hepatitis C virus infection is characterised by enhanced oxidative
      stress, which can be measured quantitatively by plasma oxysterol concentration.
      These molecules may affect lipid metabolism through the activation of Liver X
      Receptors. Hepatitis C virus exploits host lipid metabolism to facilitate its
      replication and diffusion. In our study we aimed to evaluate and highlight the
      potential pathogenetic role of oxysterols, 7-ketocholesterol and 7-beta
      hydroxycholesterol, in hepatitis C virus-related lipid dysmetabolism. METHODS:
      The study was performed in 42 patients with chronic hepatitis C (93% genotype 1b)
      and 38 non-alcoholic fatty liver disease patients. Plasma oxysterols 7
      ketocholesterol and 7-beta-hydroxycholesterol were determined by isotope dilution
      gas chromatography/mass spectrometry. RESULTS: Gas chromatography/mass
      spectrometry revealed higher 7-ketocholesterol (71.2 +/- 77.3 vs 30.4 +/- 14.5;
      p<0.005) and 7-beta-hydroxycholesterol (23.7 +/- 20.6 vs 11.5 +/- 4.9; p<0.001)
      plasma levels in hepatitis C virus patients. Furthermore, multivariate regression
      analysis highlighted an inverse independent correlation between high oxysterol
      levels and low low-density lipoprotein cholesterol (p=0.01 for 7-beta
      hydroxycholesterol; p=0.02 for 7-ketocholesterol) in the hepatitis C virus group;
      in contrast, the non-alcoholic fatty liver disease group showed a direct
      correlation between oxysterol levels and low-density lipoprotein-cholesterol
      (p<0.001 for 7-beta-hydroxycholesterol; p=0.002 for 7-ketocholesterol).
      CONCLUSION: These different correlations reveal profound differences in lipid
      dysmetabolism between chronic hepatitis C and non-alcoholic fatty liver disease
      patients.

PMID- 22154951
TI  - Specific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of
      MCPH1 revealed by complex structure.
AB  - MCPH1 is especially important for linking chromatin remodeling to DNA damage
      response. It contains three BRCT (BRCA1-carboxyl terminal) domains. The N
      terminal region directly binds with chromatin remodeling complex SWI-SNF, and the
      C-terminal BRCT2-BRCT3 domains (tandem BRCT domains) are involved in cellular DNA
      damage response. The MCPH1 gene associates with evolution of brain size, and its
      variation can cause primary microcephaly. In this study we solve the crystal
      structures of MCPH1 natural variant (A761) C-terminal tandem BRCT domains alone
      as well as in complex with gammaH2AX tail. Compared with other structures of
      tandem BRCT domains, the most significant differences lie in phosphopeptide
      binding pocket. Additionally, fluorescence polarization assays demonstrate that
      MCPH1 tandem BRCT domains show a binding selectivity on pSer +3 and prefer to
      bind phosphopeptide with free COOH-terminus. Taken together, our research
      provides new structural insights into BRCT-phosphopeptide recognition mechanism.

PMID- 22154952
TI  - Nurse educators and professional ethics--ethical principles and their
      implementation from nurse educators' perspectives.
AB  - This study describes nurse educators' knowledge of the ethical principles of
      professional codes of ethics and educators' assessment of the implementation of
      principles of fairness and human respect. Data for this study was collected from
      nurse educators in Finland. The data was analyzed by SPSS (15.0) for Windows. A
      total of 342 nurse educators participated. The response rate was 46%. Nurse
      educators knew well the ethical principles of professional codes governing their
      work. Older and more experienced educators knew the principles better than
      younger and less experienced. According to the educators the principle of
      fairness was implemented the best whereas fair treatment of nurse educators and
      respect for educators' opinions in the society were implemented the weakest.
      Educators who knew the principles well assessed themselves to act in a fairer way
      and to respect other persons' opinions in a better way than educators who knew
      these principles less well. They also felt themselves to be better treated than
      educators having less knowledge of the principles. These findings can be utilized
      to develop nurse educators' ethics education. Further research should focus on
      students', colleagues' and superiors' assessments of nurse educators' ethical
      knowledge base to gain comparative data on the phenomenon.

PMID- 22154953
TI  - Mental health behaviours among undergraduate nursing students: issues for
      consideration.
AB  - It is clear that many university students across all disciplines (including
      nursing) experience a diverse range of intrapersonal and interpersonal
      difficulties. Some students are exposed to circumstances and expectations that
      may place them at risk for mental health or substance use disorders or exacerbate
      pre-existing problems. Research shows increasing rates of diagnosable mental
      health conditions such as substance use disorders, depression, personality
      disorders, and behavioural challenges that present themselves while students are
      undertaking their university education. It is therefore important that nurse
      educators are able to identify student problems in both academic and clinical
      settings, so that symptoms, signs and inexplicable behaviours are not ignored,
      and steps towards referral and early intervention are taken. In this paper, we
      discuss rates of mental health problems and substance use among undergraduate
      nursing students, problems in the teaching-learning and clinical settings which
      nurse educators are likely to witness, and the consequences of unacknowledged
      psychiatric difficulties and problematic behaviours.

PMID- 22154954
TI  - Olfaction in dragonflies: electrophysiological evidence.
AB  - The problem of olfaction in Paleoptera (Odonata, Ephemeroptera) cannot be
      considered fully elucidated until now. These insects have been traditionally
      considered anosmic, because their brain lacks glomerular antennal lobes,
      typically involved in Neoptera odor perception. In order to understand if the
      presumed coeloconic olfactory receptors described on the antennal flagellum of
      adult Odonata are really functioning, we performed an electrophysiological
      investigation with electroantennogram (EAG) and single cell recordings (SCR),
      using Libellula depressa L. (Odonata, Libellulidae) as a model species. Odors
      representing different chemical classes such as (Z)-3-hexenyl acetate (acetate
      ester), (E)-2-hexenal, octanal (aldehydes), (Z)-3-hexen-1-ol (alcohol), propionic
      acid, butyric acid (carboxylic acids), and 1,4-diaminobutane (amine) were tested.
      Most of the tested chemicals elicited depolarizing EAG responses in both male and
      female antennae; SCR show unambiguously for the first time the presence of
      olfactory neurons in the antennae of L. depressa and strongly support the
      olfactory function of the coeloconic sensilla located on the antennal flagellum
      of this species. Electrophysiological activity may not necessarily indicate
      behavioral activity, and the biological role of olfactory responses in Odonata
      must be determined in behavioral bioassays. This study represents a starting
      point for further behavioral, electrophysiological, neuroanatomical and molecular
      investigation on Odonata olfaction, a research field particularly interesting
      owing to the basal position of Paleoptera, also for tracing evolutionary trends
      in insect olfaction.

PMID- 22154955
TI  - Natriuresis and diuretic hormone synergism in R. prolixus upper Malpighian
      tubules is inhibited by the anti-diuretic hormone, RhoprCAPA-alpha2.
AB  - Insects contain an array of hormones that coordinate the actions of the excretory
      system to achieve osmotic and ionic balance. In the hematophagous insect,
      Rhodnius prolixus, two diuretic hormones have been identified, serotonin (5HT)
      and a corticotropin releasing factor-related peptide (RhoprDH), and both lead to
      an increase in fluid secretion by Malpighian tubules (MTs). However, only 5HT
      activates reabsorption by the lower MTs to recover K(+) and Cl(-). An anti
      diuretic hormone (RhoprCAPA-alpha2) is believed to coordinate the cessation of
      the rapid diuresis following blood meal engorgement. However, the role of
      RhoprCAPA-alpha2 on fluid secretion by MTs stimulated by RhoprDH was previously
      unknown. Here we demonstrate that, unlike the inhibitory effect on 5HT-stimulated
      secretion by MTs, RhoprCAPA-alpha2 does not inhibit secretion stimulated by
      RhoprDH although it does abolish the synergism that occurs between the two
      diuretic hormones. In addition, we show that the natriuresis elicited by either
      diuretic hormone is reduced by RhoprCAPA-alpha2. Using electrophysiological
      tools, we investigate the possible mechanism by which this complex regulatory
      pathway is achieved. Analysis of the pH of secreted fluid as well as the
      triphasic response in transepithelial potential in MTs treated with diuretic
      hormones, suggests that RhoprCAPA-alpha2 does not inhibit the V-type H(+) ATPase.
      Taken together, these results indicate that RhoprCAPA-alpha2 functions to reduce
      the rapid diuresis following blood feeding, and in addition, it inhibits the
      natriuresis associated with diuretic hormone stimulated MTs. This may reflect an
      important regulatory mechanism related to the slow diuresis that occurs as the
      K(+)-rich blood cells are digested.

PMID- 22154956
TI  - Corpus callosum alterations in very preterm infants: perinatal correlates and 2
      year neurodevelopmental outcomes.
AB  - The aim of this study was to relate altered corpus callosum (CC) integrity in 106
      very preterm (VPT) infants (<30 weeks' gestational age or <1250 g birth weight)
      at term equivalent to perinatal predictors and neurodevelopmental outcomes at two
      years. T1 and diffusion magnetic resonance images were obtained. The CC was
      traced, and divided into six sub-regions for cross-sectional area and shape
      analyses. Fractional anisotropy, mean, axial and radial diffusivity were sampled
      within the CC, and probabilistic tractography was performed. Perinatal predictors
      were explored. The Bayley Scales of Infant Development (BSID-II) was administered
      at two years. Intraventricular hemorrhage was associated with a smaller genu and
      altered diffusion values within the anterior and posterior CC of VPT infants.
      White matter injury was associated with widespread alterations to callosal
      diffusion values, especially posteriorly, and radial diffusivity was particularly
      elevated, indicating altered myelination. Reduced CC tract volume related to
      lower gestational age, particularly posteriorly. Reduced posterior callosal skew
      was associated with postnatal corticosteroid exposure. This more circular CC was
      associated with delayed cognitive development. Higher diffusivity, particularly
      in splenium tracts, was associated with impaired motor development. This study
      elucidates perinatal predictors and adverse neurodevelopmental outcomes
      associated with altered callosal integrity in VPT infants.

PMID- 22154957
TI  - Disrupted modular brain dynamics reflect cognitive dysfunction in Alzheimer's
      disease.
AB  - The relation between pathology and cognitive dysfunction in dementia is still
      poorly understood, although disturbed communication between different brain
      regions is almost certainly involved. In this study we combine magneto
      encephalography (MEG) and network analysis to investigate the role of functional
      sub-networks (modules) in the brain with regard to cognitive failure in
      Alzheimer's disease. Whole-head resting-state (MEG) was performed in 18 Alzheimer
      patients (age 67 +/- 9, 6 females, MMSE 23 +/- 5) and 18 healthy controls (age 66
      +/- 9, 11 females, MMSE 29 +/- 1). We constructed functional brain networks based
      on interregional synchronization measurements, and performed graph theoretical
      analysis with a focus on modular organization. The overall modular strength and
      the number of modules changed significantly in Alzheimer patients. The parietal
      cortex was the most highly connected network area, but showed the strongest
      intramodular losses. Nonetheless, weakening of intermodular connectivity was even
      more outspoken, and more strongly related to cognitive impairment. The results of
      this study demonstrate that particularly the loss of communication between
      different functional brain regions reflects cognitive decline in Alzheimer's
      disease. These findings imply the relevance of regarding dementia as a functional
      network disorder.

PMID- 22154959
TI  - Children's reasoning about spatial relational similarity: the effect of alignment
      and relational complexity.
AB  - We investigated 4- and 5-year-old children's mapping strategies in a spatial
      task. Children were required to find a picture in an array of three identical
      cups after observing another picture being hidden in another array of three cups.
      The arrays were either aligned one behind the other in two rows or placed side by
      side forming one line. Moreover, children were rewarded for two different mapping
      strategies. Half of the children needed to choose a cup that held the same
      relative position as the rewarded cup in the other array; they needed to map left
      left, middle-middle, and right-right cups together (aligned mapping), which
      required encoding and mapping of two relations (e.g., the cup left of the middle
      cup and left of the right cup). The other half needed to map together the cups
      that held the same relation to the table's spatial features-the cups at the
      edges, the middle cups, and the cups in the middle of the table (landmark
      mapping)-which required encoding and mapping of one relation (e.g., the cup at
      the table's edge). Results showed that children's success was constellation
      dependent; performance was higher when the arrays were aligned one behind the
      other in two rows than when they were placed side by side. Furthermore, children
      showed a preference for landmark mapping over aligned mapping.

PMID- 22154958
TI  - Neuropeptide Y and extracellular signal-regulated kinase mediate injury-induced
      neuroregeneration in mouse olfactory epithelium.
AB  - In the olfactory epithelium (OE), injury induces ATP release, and subsequent
      activation of P2 purinergic receptors by ATP promotes neuroregeneration by
      increasing basal progenitor cell proliferation. The molecular mechanisms
      underlying ATP-induced increases in OE neuroregeneration have not been
      established. In the present study, the roles of neuroproliferative factors
      neuropeptide Y (NPY) and fibroblast growth factor 2 (FGF2), and p44/42
      extracellular signal-regulated kinase (ERK) on ATP-mediated increases of
      neuroregeneration in the OE were investigated. ATP increased basal progenitor
      cell proliferation in the OE via activation of P2 purinergic receptors in vitro
      and in vivo as monitored by incorporation of 5'-ethynyl-2'-deoxyuridine, a
      thymidine analog, into DNA, and proliferating cell nuclear antigen (PCNA) protein
      levels. ATP induced p44/42 ERK activation in globose basal cells (GBCs) but not
      horizontal basal cells (HBCs). ATP differentially regulated p44/42 ERK over time
      in the OE both in vitro and in vivo with transient inhibition (5-15 min) followed
      by activation (30 min-1 h) of p44/42 ERK. In addition, ATP indirectly activated
      p44/42 ERK in the OE via ATP-induced NPY release and subsequent activation of NPY
      Y1 receptors in the basal cells. There were no synergistic effects of ATP and NPY
      or FGF2 on OE neuroregeneration. These data clearly have implications for the
      pharmacological modulation of neuroregeneration in the olfactory epithelium.

PMID- 22154960
TI  - Real-time image-based rigid registration of three-dimensional ultrasound.
AB  - Registration of three-dimensional ultrasound (3DUS) volumes is necessary in
      several applications, such as when stitching volumes to expand the field of view
      or when stabilizing a temporal sequence of volumes to cancel out motion of the
      probe or anatomy. Current systems that register 3DUS volumes either use external
      tracking systems (electromagnetic or optical), which add expense and impose
      limitations on acquisitions, or are image-based methods that operate offline and
      are incapable of providing immediate feedback to clinicians. This paper presents
      a real-time image-based algorithm for rigid registration of 3DUS volumes designed
      for acquisitions in which small probe displacements occur between frames.
      Described is a method for feature detection and descriptor formation that takes
      into account the characteristics of 3DUS imaging. Volumes are registered by
      determining a correspondence between these features. A global set of features is
      maintained and integrated into the registration, which limits the accumulation of
      registration error. The system operates in real-time (i.e. volumes are registered
      as fast or faster than they are acquired) by using an accelerated framework on a
      graphics processing unit. The algorithm's parameter selection and performance is
      analyzed and validated in studies which use both water tank and clinical images.
      The resulting registration accuracy is comparable to similar feature-based
      registration methods, but in contrast to these methods, can register 3DUS volumes
      in real-time.

PMID- 22154961
TI  - Feature-based interpolation of diffusion tensor fields and application to human
      cardiac DT-MRI.
AB  - Diffusion tensor interpolation is an important issue in the application of
      diffusion tensor magnetic resonance imaging (DT-MRI) to the human heart, all the
      more as the points representing the myocardium of the heart are often sparse. We
      propose a feature-based interpolation framework for the tensor fields from
      cardiac DT-MRI, by taking into account inherent relationships between tensor
      components. In this framework, the interpolation consists in representing a
      diffusion tensor in terms of two tensor features, eigenvalues and orientation,
      interpolating the Euler angles or the quaternion relative to tensor orientation
      and the logarithmically transformed eigenvalues, and reconstructing the tensor to
      be interpolated from the interpolated eigenvalues and tensor orientations. The
      results obtained with the aid of both synthetic and real cardiac DT-MRI data
      demonstrate that the feature-based schemes based on Euler angles or quaternions
      not only maintain the advantages of Log-Euclidean and Riemannian interpolation as
      for preserving the tensor's symmetric positive-definiteness and the monotonic
      determinant variation, but also preserve, at the same time, the monotonicity of
      fractional anisotropy (FA) and mean diffusivity (MD) values, which is not the
      case with Euclidean, Cholesky and Log-Euclidean methods. As a result, both
      interpolation schemes remove the phenomenon of FA collapse, and consequently
      avoid introducing artificial fiber crossing, with the difference that the
      quaternion is independent of coordinate system while Euler angles have the
      property of being more suitable for sophisticated interpolations.

PMID- 22154962
TI  - Distinct roles of the 'shared pain' and 'theory of mind' networks in processing
      others' emotional suffering.
AB  - The brain mechanisms involved in processing another's physical pain have been
      extensively studied in recent years. The link between understanding others'
      physical pain and emotional suffering is less well understood. Using whole brain
      analysis and two separate functional localizers, we characterized the neural
      response profiles of narrative scenarios involving physical pain (PP), and
      scenarios involving emotional pain (EP) with functional magnetic resonance
      imaging (fMRI). Whole brain analyses revealed that PP narratives activated the
      Shared Pain network, and that the brain regions responsible for processing EP
      overlapped substantially with brain regions involved in Theory of Mind. Region of
      interest (ROI) analysis provided a finer-grained view. Some regions responded to
      stories involving physical states, regardless of painful content (secondary
      sensory regions), some selectively responded to both emotionally and physically
      painful events (bilateral anterior thalamus and anterior middle cingulate
      cortex), one brain region responded selectively to physical pain (left insula),
      and one brain region responded selectively to emotional pain (dorsomedial
      prefrontal cortex). These results replicated in two groups of participants given
      different explicit tasks. Together, these results clarify the distinct roles of
      multiple brain regions in responding to others who are in physical or emotional
      pain.

PMID- 22154963
TI  - Biliary papillomatosis in three Caucasian patients in a Western centre.
AB  - INTRODUCTION: Biliary papillomatosis (BP) is a rare condition with a strong
      potential for malignant transformation and cases from Western centres are
      sparse.(1) We discuss the presentation, investigation and management of this
      condition in three Caucasian patients and present a review of the existing
      literature on BP. PATIENTS AND METHODS: The case notes of three Caucasian
      patients with BP who presented to our tertiary referral centre were reviewed.
      Their case histories, investigations and managements are presented. A search of
      MEDLINE, PubMed and Cochrane databases was performed to review relevant
      literature around BP. DISCUSSION: BP is a rare condition characterised by
      multiple papillary adenomas involving the biliary tree which lead to recurrent
      attacks of cholangitis. It is a low-grade neoplasm with high malignant potential
      and should be regarded as a pre-malignant lesion.

PMID- 22154964
TI  - Muscle FBPase binds to cardiomyocyte mitochondria under glycogen synthase kinase
      3 inhibition or elevation of cellular Ca2+ level.
AB  - A growing body of research suggests that fructose 1,6-bisphosphatase (FBPase)
      might be involved in regulation of cell mortality/survival. However, the precise
      role of FBPase in the process remains unknown. Here, we show for the first time
      that in HL-1 cardiomyocytes, inhibition of glycogen synthase kinase-3 results in
      translocation of FBPase to mitochondria. In vitro experiments demonstrate that
      FBPase reduces the rate of calcium-induced mitochondrial swelling, affects ATP
      synthesis and interacts with mitochondrial proteins involved in regulation of
      volume and energy homeostasis. We suggest that FBPase might be engaged in a
      regulation of cell survival by influencing mitochondrial function.

PMID- 22154965
TI  - Antinociceptive and anti-inflammatory potential of extract and isolated compounds
      from the leaves of Salvia officinalis in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia officinalis L. has been used as a
      traditional herbal medicine for gastric disturbances and inflammatory processes.
      This study investigated the toxicological, antinociceptive and anti-inflammatory
      effects of the hydroalcoholic extract (HE) from leaves of Salvia officinalis and
      its isolated compounds in mice. MATERIALS AND METHODS: Mice were treated with HE
      before the induction of nociceptive response by chemical agents (acetic-acid,
      formalin, glutamate, capsaicin and cinnamaldehyde). Total leukocytes and plasma
      extravasation induced by acetic acid and paw oedema induced by glutamate,
      capsaicin and cinnamaldehyde were also measured. The antinociceptive effect of
      carnosol and ursolic acid/oleanolic acid were evaluated on formalin and
      cinnamaldehyde models. RESULTS: In the acute toxicity test the value of estimated
      LD50 for HE was 44.7579 g/kg. Oral administration of HE (10, 30 and 100 mg/kg)
      inhibited the number of writhings, total leukocytes and plasma extravasation
      induced by acetic acid. In the formalin test, HE reduced both neurogenic and
      inflammatory phases, effect that was affected by naloxone. The glutamate-,
      capsaicin- and cinnamaldehyde-induced nociception and paw oedema were reduced by
      HE at doses that did not affect the locomotor activity of mice in the open field
      test. Carnosol (10mg/kg) and ursolic acid/oleanolic acid (30 mg/kg) inhibited the
      inflammatory phase of formalin and the nociception and mechanical allodynia
      induced by cinnamaldehyde. CONCLUSIONS: These results demonstrate that HE
      presents significant anti-inflammatory and also antinociceptive effects on
      chemical behavioral models of nociception that involves an opioid mechanism. In
      addition, carnosol and ursolic acid/oleanolic acid contained in this plant
      appears to contribute for the antinociceptive property of the extract, possibly
      through a modulatory influence on TRPA1-receptors. However, further studies
      regarding the precise site and the mechanism of action of HE and carnosol and
      ursolic acid/oleanolic acid merited exploring further.

PMID- 22154966
TI  - Pharmacological, genotoxic and phytochemical properties of selected South African
      medicinal plants used in treating stomach-related ailments.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The evaluated medicinal plants are used in South
      African traditional medicine in treating stomach-related ailments. AIMS OF THE
      STUDY: The study aimed at evaluating the pharmacological, genotoxic and
      phytochemical properties of the seven selected medicinal plants used for treating
      stomach-related ailments. MATERIALS AND METHODS: Ethyl acetate (EtOAc), ethanol
      (EtOH) 70% and water extracts of the selected plant parts were evaluated for
      their antimicrobial and anthelmintic activities using microdilution assays. Gram
      positive bacteria (Enterococcus faecalis and Staphylococcus aureus), Gram
      negative bacterium (Escherichia coli) and Candida albicans were used for
      antimicrobial assays. Caenorhabditis elegans was used for the anthelmintic assay.
      Plant extracts were also assayed for their cyclooxygenase-inhibitory activity
      against cyclooxygenase-1 and -2 enzymes. The Ames test was used to evaluate the
      genotoxicity of the plant extracts. A spectrophotometric method was used to
      determine the total phenolics, gallotannins, flavonoids and saponins. RESULTS:
      Twelve extracts exhibited minimum inhibitory concentration (MIC) <1 mg/mL against
      the bacterial test strains, and five extracts exhibited MIC <1 mg/mL against
      Candida albicans. The EtOAc extract of Tetradenia riparia had the best minimum
      lethal concentration (MLC) value (0.004 mg/mL) against Caenorhabditis elegans.
      All the EtOAc extracts exhibited percentage inhibition in the range of 50.7-94.7%
      against COX-1 and -2 enzymes at 250 MUg/mL. All the plant extracts were non
      mutagenic towards Salmonella typhimurium tester strains TA98, TA100 and TA1537
      without metabolic activation. Phytochemical analysis revealed relatively high
      amounts of total phenolics, gallotannins and flavonoids in the evaluated plant
      extracts. CONCLUSIONS: The general pharmacological activities exhibited by some
      of the plant extracts in this study support the traditional uses of the selected
      plants in treating stomach-related ailments. The Ames test showed that all the
      plant extracts were non-mutagenic but cytotoxicity tests are needed to ascertain
      the safety for long-term consumption.

PMID- 22154967
TI  - Panax notoginsenoside produces neuroprotective effects in rat model of acute
      spinal cord ischemia-reperfusion injury.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Acute spinal cord ischemia-reperfusion injury
      (SCII) is associated with pathological changes, including inflammation, edema,
      and neuronal apoptosis. Panax notoginsenoside (PNS), an important traditional
      Chinese medicine, has shown a variety of beneficial effects, including
      homeostasis maintenance, anti-myocardial ischemia activities, and neuroprotective
      functions. However, whether it can produce neuroprotective effects in SCII and
      the underlying mechanisms remain largely elusive. AIM OF THE STUDY: In the
      present study, we investigated the effects of PNS on neurological and
      histopathological changes after SCII as well as the underlying mechanisms.
      MATERIALS AND METHODS: Sixty-four adult rats were randomly assigned into one of
      the four groups: the sham group, the ischemic group, the PNS group, and the
      Methylprednisolone group. A rat model of SCII was adopted from a commonly used
      protocol that was initially proposed by Zivin. Neurological function was
      evaluated with the Basso, Beattie and Bresnahan (BBB) locomotor rating scale.
      Histopathological changes were examined with hematoxylin and eosin staining as
      well as Nissl staining. Immunohistochemistry and Western blot were conducted to
      compare the changes in tumor necrosis factor-alpha, interleukin-1beta,
      interleukin-10, aquaporin-4 (AQP-4), member 6 of the TNF receptor superfamily
      (Fas), and Fas ligand (FasL) in the spinal cord. Finally, neuronal apoptosis was
      measured by electron microscopy. RESULTS: The BBB scores of the PNS-treated
      injured animals were significantly increased. The gross histopathological
      examination showed restored neuronal morphology and increased number of neurons
      after the PNS treatment. The PNS treatment decreased SCII-induced up-regulation
      of cytokine levels. In addition, PNS suppressed the increased expression of AQP-4
      after SCII, suggesting an anti-edema effect. Finally, PNS treatment inhibited
      injury-induced apoptosis and reduced the expression levels of apoptosis-related
      proteins, Fas and FasL, confirming its anti-apoptosis effects against SCII.
      CONCLUSION: The current findings suggest that PNS produces robust neuroprotective
      effects in spinal cord ischemia-reperfusion injury, and this role may be mediated
      by its anti-inflammation, anti-edema, and anti-apoptosis actions.

PMID- 22154968
TI  - An inconvenient truth: global worming and anthelmintic resistance.
AB  - Over the past 10-15 years, we have witnessed a rapid increase in both the
      prevalence and magnitude of anthelmintic resistance, and this increase appears to
      be a worldwide phenomenon. Reports of anthelmintic resistance to multiple drugs
      in individual parasite species, and in multiple parasite species across virtually
      all livestock hosts, are increasingly common. In addition, since the introduction
      of ivermectin in 1981, no novel anthelmintic classes were developed and
      introduced for use in livestock until recently with the launch of monepantel in
      New Zealand. Thus, livestock producers are often left with few options for
      effective treatment against many important parasite species. While new
      anthelmintic classes with novel mechanisms of action could potentially solve this
      problem, new drugs are extremely expensive to develop, and can be expected to be
      more expensive than older drugs. Thus, it seems clear that the "Global Worming"
      approach that has taken hold over the past 40-50 years must change, and livestock
      producers must develop a new vision for parasite control and sustainability of
      production. Furthermore, parasitologists must improve methods for study design
      and data analysis that are used for diagnosing anthelmintic resistance,
      especially for the fecal egg count reduction test (FECRT). Currently, standards
      for diagnosis of anthelmintic resistance using FECRT exist only for sheep. Lack
      of standards in horses and cattle and arbitrarily defined cutoffs for defining
      resistance, combined with inadequate analysis of the data, mean that errors in
      assigning resistance status are common. Similarly, the lack of standards makes it
      difficult to compare data among different studies. This problem needs to be
      addressed, because as new drugs are introduced now and in the future, the lack of
      alternative treatments will make early and accurate diagnosis of anthelmintic
      resistance increasingly important.

PMID- 22154969
TI  - Use of Artemisia annua as a natural coccidiostat in free-range broilers and its
      effects on infection dynamics and performance.
AB  - This work investigated the preventive effect of Artemisia annua L. dried leaves
      supplied as a botanical coccidiostat to two broiler genotypes reared in a Danish
      free-range system in a factorial experiment (two genotypes and +/- supplement of
      dried A. annua leaves). The genotypes White Bresse L40, a pure slow-growing line,
      and Kosmos 8 Ross, a hybrid genotype with medium growing characteristics, were
      used. Broilers were raised indoor until 29-days-old and kept free of parasites.
      Twelve groups of 30 randomly selected broilers were placed in the range forming
      three replicates for each treatment combination. The paddocks were cultivated
      with a mix of grass and clover. A separate group of broilers was naturally
      infected with Eimeria spp. oocysts and five animals nominated as "seeders" were
      introduced to the above mentioned 12 groups, 10 days after its formation, with
      each group consisting of 35 animals per plot. This infection strategy was meant
      to imitate the transmission pathway observed at farm level. Ten individual birds
      from each of the 12 groups, in total 120 animals of mixed sex, were monitored
      twice weekly for 30 days for oocysts excretion. PCR of pooled faecal samples,
      oocyst morphology and localization upon necropsy were used to identify the
      Eimeria species involved in the infection. In general, broilers from both
      genotypes in the range coped well with a coccidia infection caused by Eimeria
      acervulina and Eimeria maxima as no clinical symptoms, or deaths, were reported
      during the experiment. In general, broilers supplemented with A. annua dried
      leaves showed a significantly (p<0.05) reduced number of excreted oocysts during
      the infection with no interaction to genotype. Females generally had a
      significantly higher shedding of oocysts than males (p<0.05). The overall body
      weight gain and the daily weight gain when infection was subdued showed a three
      way interaction among genotype, sex and treatment - accounted mainly for the fact
      that Kosmos females responded positively to the Artemisia treatment while Kosmos
      males responded negatively, and only minor differences were found between sexes
      for the White Bresse genotype. In conclusion, supply of A. annua dried leaves as
      a botanical coccidiostat significantly reduced oocyst output in free ranged
      broilers and thus may form part of a strategy to prevent commercial losses.

PMID- 22154970
TI  - Assessment of three methods for multilocus fragment typing of Cryptosporidium
      parvum from domestic ruminants in north west Spain.
AB  - The performance of three different methods, capillary electrophoresis (CE), high
      resolution slab-gel electrophoresis and sequencing, for PCR fragment size
      analysis of two Cryptosporidium parvum microsatellite regions, ML1 and ML2, was
      investigated by analysing 27 isolates from calves and 14 from lambs. To assess
      genetic variability of this protozoan in domestic ruminants in north west Spain,
      results were combined with sequence analysis of the 60 kDa glycoprotein (GP60)
      gene creating a multilocus type and analysed by farm and host species. CE showed
      greater overall typability (T), discriminatory power and ease of use than slab
      gel electrophoresis and sequencing which were both affected by PCR stutter,
      especially at ML2. CE fragment sizes were consistently 4 bp longer compared to
      sequencing which is considered the gold standard for allele sizing but which gave
      the lowest typability; CE sizes were therefore adjusted. Only three alleles were
      identified at the ML1 locus (ML1-238, ML1-229 and ML1-226). The ML2 locus was
      more polymorphic and eight alleles were found (ML2-235, ML2-233, ML2-231, ML2
      229, ML2-227, ML2-225, ML2-201 and ML2-176). Adjusted ML1 and ML2 CE fragment
      sizes were combined with GP60 subtype for 37 of the 41 C. parvum isolates which
      were typable at all three loci (T=0.90): nine multilocus types (MLTs) were
      identified. The discriminatory power of the 3-locus typing method was 0.83.
      Greater genetic variability was observed in calf isolates (7 MLTs) than in those
      from lambs (4 MLTs) although more calf isolates were studied. The most common MLT
      in cattle was MLT1 (ML1-238, ML2-231, GP60 subtype IIaA15G2R1), while MLT3 (ML1
      238, ML2-227, GP60 IIaA16G3R1) was predominant in lambs. Our findings demonstrate
      that high discrimination can be achieved by means of multilocus typing. CE
      appears to be an economic and rapid option for performing microsatellite fragment
      size analysis offering good typability, discrimination and ease of use but may
      require calibration to sequenced standards.

PMID- 22154971
TI  - Preserving new anthelmintics: a simple method for estimating faecal egg count
      reduction test (FECRT) confidence limits when efficacy and/or nematode
      aggregation is high.
AB  - As it has been 30 years since a new anthelmintic class was released, it is
      appropriate to review management practices aimed at slowing the development of
      anthelmintic resistance to all drug classes. Recommendations to delay
      anthelmintic resistance, provide refugia and the use of a simulation model were
      reviewed to find optimum treatment strategies that maintain nematode control.
      Simulated Australian conditions indicated that a common successful low-risk
      treatment program was a rapid rotation between a "triple-combination" product
      (benzimidazole+levamisole+abamectin) and a new high-efficacy drug (monepantel).
      Where Haemonchus contortus was a threat, moxidectin was required at critical
      times because of its persistent activity against this parasite. Leaving up to 4%
      of adult sheep untreated provided sufficient "refugia" for non-selected worms to
      reduce the risk of selecting for anthelmintic resistance without compromising
      nematode control. For a new anthelmintic, efficacy estimated by faecal egg count
      reduction (FECR) is likely to be at or close to 100%, however using current
      methods the 95% confidence limits (CL) for 100% are incorrectly determined as
      100%. The fewer eggs counted pre-treatment, the more likely an estimate of 100%
      will occur, particularly if the true efficacy is >90%. A novel way to determine
      the lower-CL (LCL) for 100% efficacy is to reframe FECR as a binomial proportion,
      i.e. define: n and x as the total number of eggs counted (rather than eggs per
      gram of faeces) for all pre-treatment and post-treatment animals, respectively; p
      the proportion of resistant eggs is p = x/n and percent efficacy is 100 *(1-p)
      (assuming equal treatment group sizes and detection levels, pre- and post
      treatment). The LCL is approximated from the cumulative inverse beta distribution
      by: 95%LCL=100 *(1-(BETAINV(0.975, x+1, n-x+1))). This method is simpler than the
      current method, independent of the number of animals tested, and demonstrates
      that for 100% efficacy at least 37 eggs (not eggs per gram) need to be counted
      pre-treatment before the LCL can exceed 90%. When nematode aggregation is high,
      this method can be usefully applied to efficacy estimates lower than 100%, and in
      this case the 95% upper-CL (UCL) can be estimated by: 95% UCL = 100
      *(1((BETAINV(0.025, x+1, n-x+1))), with the LCL approximated as described above.
      A simulation study to estimate the precision and accuracy of this method found
      that the more conservative 99%CL was optimum; in this case 0.975 and 0.025 are
      replaced by 0.995 and 0.005 to estimate the LCL and UCL, respectively.

PMID- 22154972
TI  - Gene expression in rabbit appendices infected with Eimeria coecicola.
AB  - Eimeria coecicola causes intestinal coccidiosis in rabbits and, thereby, enormous
      economic losses in rabbit farms. Here, we investigate the final target site of E.
      coecicola, the appendix of rabbits, at the level of gene expression. Rabbits,
      orally infected with E. coecicola, begin to shed parasitic oocysts with their
      feces on day 5 p.i., and approximately 1.1 million oocysts are maximally shedded
      on day 7 p.i. At maximal shedding, the appendix has increased in size by about 2
      3-folds and reveals increased hemorrhage which is associated with increases in
      nitrite/nitrate, malondialdehyde and catalase activity and a decrease in
      glutathione. Agilent 2-color oligo whole rabbit genome microarray, in combination
      with quantitative real-time PCR, detects 45 and 36 genes whose expression is more
      than 2-fold up- and down-regulated, respectively, by E. coecicola infection on
      day 7 p.i. The most dramatic increase by approximately 50-fold reveals the mRNA
      of the pro- and anti-inflammatory pleiotropic cytokine interleukin 6 (IL-6),
      whereas the largest decrease by approximately 13-fold is detected for mRNAs
      encoding for DBP, SULT3A1, CRP and glutathione-S transferase. Also, there are up-
      and down-regulations in the expression of genes encoding diverse regions of
      antibodies. Our data suggest that IL-6 plays a central role in the infection of
      the appendix of rabbits by E. coecicola, presumably involved in both pathological
      injuries, host defences and healing processes.

PMID- 22154973
TI  - Self-esteem fluctuations and cardiac vagal control in everyday life.
AB  - It has been proposed that self-esteem buffers threat-responding. The same effect
      is ascribed to the vagus nerve, which is a primary nerve of the parasympathetic
      nervous system. Consequently, it has been suggested that self-esteem and cardiac
      vagal tone are interconnected on a trait, as well as on a state, level. In this
      study, we examined the relationship of vagal cardiac control and self-esteem
      fluctuations across a single day using ecological momentary assessment. Eighty
      four participants were recruited, and self-esteem, negative affect, and vagal
      tone were recorded throughout a 22-hour period. Men provided higher self-esteem
      ratings than women, but the negative relationship between self-esteem and
      negative affect was stronger in women. Moreover, controlling for potential
      confounds (e.g., age, BMI, depressive symptoms, smoking status, regular physical
      activity), we observed that for men, self-esteem was significantly positively
      associated with cardiac vagal tone, whereas for women it was not. These findings
      suggest that the relationship between self-esteem and vagal innervation of the
      heart during daily life is sex-specific and might involve different central
      autonomic pathways for men and women, respectively.

PMID- 22154974
TI  - Loss to follow up from isoniazid preventive therapy among adults attending HIV
      voluntary counseling and testing sites in Uganda.
AB  - Among HIV-infected adults attending non-governmental organization voluntary
      counseling and testing (VCT) sites in Uganda that provide a nine-month course of
      isoniazid preventive treatment (IPT), we report on loss to follow-up (LTFU) and
      its associated risk factors. The design was a retrospective cohort study of
      program data spanning a three year period (2006-2008). A total of 586 IPT
      patients were enrolled of whom 335 (57.1%) were females with a mean age of 34
      years. Of those starting IPT, 341 (58.1%) were lost to follow-up, 197 (33.6%)
      completed IPT, 29 (4.9%) were discontinued and 19 (3.2%) died. The return rates
      at one, three, five and seven months were 78.0% (457), 62.1% (364), 52.9% (310)
      and 33.6% (197) respectively. Being less than 30 years of age, widowed,
      separated, or divorced were found to be associated with a higher risk of loss to
      follow-up. Sudden improvement in retention on IPT was observed between the years
      2006 and 2007, although causes of the improvement are poorly understood hence the
      need for more research. At non-governmental VCT sites in Uganda, six out of ten
      individuals enrolled on IPT are lost to follow-up and efforts to reduce this
      attrition including systems strengthening might play a critical role in the
      success of IPT programs.

PMID- 22154975
TI  - Successful propagation of Alkhumra (misnamed as Alkhurma) virus in C6/36 mosquito
      cells.
AB  - Epidemiological data suggest that Alkhumra (misnamed as Alkhurma) virus (ALKV) is
      transmitted from livestock animals to humans by direct contact with animals or by
      the mosquito bites, but not by ticks. To assess the ability of the virus to
      replicate in mosquito cells, serum and plasma of seven acutely febrile patients
      with clinically suspected ALKV infection reported in Najran, Saudi Arabia in 2009
      were inoculated onto Aedes albopictus mosquito cells (C6/36) and directly
      examined with ALKV-RNA-specific real time RT-PCR as well as indirect
      immunfluorescence assay (IFA) using ALKV-specific polyclonal antibodies. The
      isolated virus was titrated in the mammalian rhesus monkey kidney cells (LLC
      MK2). Five of the seven specimens were RT-PCR- and culture-positive demonstrating
      cytopathic effects in the form of cell rounding and aggregation appearing on day
      3 post inoculation with syncytia eventually appearing on day 8 post inoculation.
      Identification of ALKV-RNA in the cell culture was confirmed with RT-PCR and IFA.
      The virus titre was 3.2*10(6) tissue culture infective dose 50 (TCID(50)) per mL.
      Three more viral passages were successfully made in the C6/36 cells. This is the
      first description of propagation of ALKV in mosquito cells.

PMID- 22154976
TI  - Lymphatic filariasis in western Ethiopia with special emphasis on prevalence of
      Wuchereria bancrofti antigenaemia in and around onchocerciasis endemic areas.
AB  - Lymphatic filariasis is known to be endemic in Gambella Region, western Ethiopia,
      but the full extent of its endemicity in other regions is unknown. A national
      mapping program for Ethiopia was initiated in 2008. This report summarizes
      initial data on the prevalence of Wuchereria bancrofti antigenaemia based on
      surveys carried out in a sampled population of 11685 individuals living in 125
      villages (112 districts) of western Ethiopia. The overall prevalence rate was
      3.7%, but high geographical clustering and variation in prevalence (ranging from
      0% to more than 50%) was found. The prevalence of hydrocele (in males) and
      lymphoedema of limbs was 0.8% and 3.6% respectively. Significantly higher
      (chi(2)=49.6; P<0.01) prevalence of antigenaemia was noted in known
      onchocerciasis endemic districts (4.7%) compared to non-onchocerciasis endemic
      districts (2.3%). Thirty-four of the 112 districts, with a population of 1547685
      in 2007, were found to be endemic. Of these, the numbers of districts with
      prevalence rates of >20%, 10-20% and 5-9% were nine, 14 and 20 respectively.
      Twenty-nine of these 34 endemic districts were found in three regions: Gambella
      Region (seven districts), Beneshangul-Gumuz Region (13 districts), and Southern
      Nations, Nationalities and Peoples' Region (SNNPR) (nine districts). The other
      five were from Amhara (two districts) and Oromia (three districts) regions. A
      tentative distribution map has been drawn to facilitate the launching of the
      Ethiopia LF elimination program.

PMID- 22154977
TI  - Entamoeba histolytica: cloning, expression and evaluation of the efficacy of a
      recombinant amebiasis cysteine proteinase gene (ACP1) antigen in minipig.
AB  - The amebiasis cysteine proteinase gene (ACP1) encoding an antigen from Entamoeba
      histolytica, as well as the recombinant ACP1, obtained by cloning and expression
      of the ACP1 gene in heterologous host Escherichia coli BL-21 (DE3), were used to
      evaluate their ability to induce immune protective responses in minipig against
      challenge infection in a minipig -E. histolytica model. There was a 64.52%
      reduction (P<0.001) in the group of recovery of challenged E. histolytica
      compared with that in the control group. Specific anti-ACP1 antibodies from
      immune protected minipig had significantly higher levels of immunoglobulin G
      (IgG) (P<0.001). Our data indicate recombinant ACP1 may be a potential target as
      a vaccine antigen.

PMID- 22154978
TI  - Comparative virulence of three Trypanosoma evansi isolates from water buffaloes
      in the Philippines.
AB  - The virulence of three Trypanosoma evansi isolates in Luzon, Visayas and Mindanao
      water buffaloes was compared determining the mortality rate, parasitemia level,
      clinical signs, and lesions on mice. A total of 51 inbred Balb/c mice (5-6 weeks
      old) were used and divided into two sets. Set A had three groups corresponding to
      three trypanosomes isolates (Luzon, Visayas, and Mindanao) with seven mice each
      whose parasitemia level, clinical signs, and lesions were noted at necropsy. Set
      B had three groups corresponding to the three isolates with ten mice each whose
      mortality was monitored. Each infected mouse was inoculated with 0.2 ml of T.
      evansi intraperitoneally and blood was examined under high power magnification.
      Their parasitemia level was determined using "Rapid Matching Method". Dead mice
      were subjected to necropsy and the lungs, liver, spleen, brain and heart were
      subjected to histopathological processing. Results showed that the mortality rate
      was highest at Day 3 for the Visayas isolates (70%), while at Day 5 for Luzon
      (90%) and Mindanao (70%) isolates. The parasitemia level of Visayas isolates
      (1*10(8.7)) reached the earliest peak at Day 4 while Luzon isolates (1*10(9)) at
      Day 6 and Mindanao isolates (1*10(8.7)) at Day 8. Statistical analysis using
      Least significant difference (LSD) revealed significant difference among
      treatment means at Days 2 and 4. All of the affected mice showed rough hair coat,
      decreased body weight, and decreased packed cell volume. The most obvious gross
      lesions observed were pale liver with petechiations and pale muscles.
      Histopathological examination revealed depletion of the red pulp and
      extramedullary hematopoiesis in the spleen. Congestion, intralesional
      trypanosomes in blood vessel and extramedullary hematopoiesis were observed in
      the liver. In the lungs non-specific lesions observed were pulmonary edema,
      congestion and hemosiderosis.

PMID- 22154979
TI  - Estimating chemical emissions from home and personal care products in China.
AB  - China's economy has grown significantly and concomitantly so has the demand for
      home and personal care (HPC) products. The detection of chemicals used in HPC
      products is increasing in profile as China strives to improve its environmental
      management. China is developing robust exposure models for use in regulatory risk
      based assessments of chemicals, including those chemicals used in HPC products.
      Accurate estimates of chemical emissions play an important role within this. A
      methodology is presented to derive spatially refined emissions from demographic
      and economic indicators with large variations in emissions calculated, showing
      product usage being higher in East and South China. The less affordable a
      product, the greater the influence per capita Gross Domestic Product has on the
      product distribution. Lastly, more spatially resolved input data highlights
      greater variation of product use. Linking product sales data with population
      density increased the observed variability in absolute usage distribution of HPC
      products at the county > province > regional > country scale.

PMID- 22154980
TI  - Improvement of metabolic parameters and vascular function by metformin in obese
      non-diabetic rats.
AB  - AIMS: Metformin is an insulin sensitizing agent with beneficial effects in
      diabetic patients on glycemic levels and in the cardiovascular system. We
      examined whether the metabolic changes and the vascular dysfunction in monosodium
      glutamate-induced obese non-diabetic (MSG) rats might be improved by metformin.
      MAIN METHODS: 16 week-old MSG rats were treated with metformin for 15 days and
      compared with age-matched untreated MSG and non-obese non-diabetic rats
      (control). Blood pressure, insulin sensitivity, vascular reactivity and
      prostanoid release in the perfused mesenteric arteriolar bed as well as nitric
      oxide production and reactive oxygen species generation in isolated mesenteric
      arteries were analyzed. KEY FINDINGS: 18-week-old MSG rats displayed higher Lee
      index, fat accumulation, dyslipidemia, insulin resistance and hyperinsulinemia.
      Metformin treatment improved these alterations. The norepinephrine-induced
      response, increased in the mesenteric arteriolar bed from MSG rats, was corrected
      by metformin. Indomethacin corrected the enhanced contractile response in MSG
      rats but did not affect metformin effects. The sensitivity to acetylcholine,
      reduced in MSG rats, was also corrected by metformin. Indomethacin corrected the
      reduced sensitivity to acetylcholine in MSG rats but did not affect metformin
      effects. The sensitivity to sodium nitroprusside was increased in preparations
      from metformin-treated rats. Metformin treatment restored both the reduced
      PGI2/TXA2 ratio and the increased reactive oxygen species generation in
      preparations from MSG rats. SIGNIFICANCE: Metformin improved the vascular
      function in MSG rats through reduction in reactive oxygen species generation,
      modulation of membrane hyperpolarization, correction of the unbalanced
      prostanoids release and increase in the sensitivity of the smooth muscle to
      nitric oxide.

PMID- 22154981
TI  - Effects of andrographolide and 14-deoxy-11,12-didehydroandrographolide on
      cultured primary astrocytes and PC12 cells.
AB  - AIMS: To test the effects of andrographolide (AP1) and 14-deoxy-11,12
      didehydroandrographolide (AP2) on pheochromocytoma cell line 12 (PC12) cells in
      an astrocyte-rich environment. MAIN METHODS: The abilities of AP1 and AP2 to
      reduce the secretion of pro-inflammatory cytokines Interleukin (IL)-1, IL-6, and
      Tumor necrosis factor (TNF)-alpha from stimulated astrocytes were tested. In
      addition, the abilities of AP1 and AP2 to reduce oxidative stress in astrocytes
      were tested using an oxidative-sensitive fluorescent dye. The reduction of
      chondroitin sulfate proteoglycan (CSPG) in stimulated astrocytes was tested using
      the dot blot method. Reduction of H(2)O(2)-induced death was tested in PC12
      cells. Astrocyte-conditioned medium (ACM) and TNF-alpha-stimulated astrocyte
      conditioned medium (SACM) were used to assess the effects of AP2 on PC12 cells
      treated with H(2)O(2). KEY FINDINGS: AP1 and AP2 reduced pro-inflammatory
      cytokines, reactive oxygen species (ROS), and CSPG in TNF-alpha stimulated
      astrocytes. AP1 protected H(2)O(2)-treated PC12 cells cultured in ACM. Co
      incubation of PC12 cells in H(2)O(2), and ACM collected from AP1 treated
      astrocytes did not prevent cell death. SIGNIFICANCE: AP1 and AP2 effectively
      ameliorated astrocytic pro-inflammatory reactions and prevented PC12 cell death
      with different efficacies. These compounds may be candidates for treatment of
      spinal-cord injury and neurodegeneration.

PMID- 22154982
TI  - Comparative proteomics profiling of a gentamicin-attenuated Leishmania infantum
      cell line identifies key changes in parasite thiol-redox metabolism.
AB  - We have previously described an attenuated line of Leishmania infantum (H-line),
      selected by culturing promastigotes in vitro in the presence of gentamicin. To
      elucidate the molecular basis for this attenuation, we undertook a comparative
      proteomic analysis using multiplex 2-dimensional (2D) difference gel
      electrophoresis. Eighteen proteins that showed significant and reproducible
      changes in expression were identified. Many of these were components of the thiol
      redox control system in Leishmania and this observation, validated by Western
      blot, prompted us to investigate the sensitivity of the attenuated line to
      oxidative stress. The attenuated line was found to be significantly more
      susceptible to hydrogen peroxide, a change which may explain the loss of
      virulence. In a direct assay of trypanothione-dependent peroxidase activity,
      hydrogen peroxide metabolism in the H-line was significantly lower than in wild
      type. Furthermore, trypanothione reductase activity was significantly lower in
      the H-line, suggesting that gentamicin selection may result in pleiotropic
      affects on thiol metabolism in Leishmania. A putative RNA-binding protein was
      very strongly up-regulated in the attenuated line, suggesting a possible target
      for gentamicin in Leishmania.

PMID- 22154983
TI  - Hexapeptide library as a universal tool for sample preparation in protein
      glycosylation analysis.
AB  - Recent analytical advancements allow for large-scale glycomics and glycan
      biomarker research with N-glycans released from complex protein mixtures of e.g.
      plasma with a wide range of protein concentrations. Protein enrichment techniques
      to obtain samples with a better representation of low-abundance proteins are
      hardy applied. In this study, hexapeptide ligands previously described for
      enrichment of low-abundance proteins in proteomics are evaluated for glycan
      analysis. A repeatable on-bead glycan release strategy was developed, and glycans
      were analyzed using capillary sieving electrophoresis on a DNA analyzer. Binding
      of proteins to the hexapeptide library occurred via the protein backbone. At
      neutral pH no discrimination between protein glycoforms was observed.
      Interestingly, glycan profiles of plasma with and without hexapeptide library
      enrichment revealed very similar patterns, despite the vast changes in protein
      concentrations in the samples. The most significant differences in glycosylation
      profiles were ascribed to a reduction in immunoglobulin-derived glycans. These
      results suggest that specific and sensitive biomarkers will be hard to access on
      the full plasma level using protein enrichment in combination with glycan
      analysis. Instead, fractionation techniques or profiling strategies on the
      glycopeptide level after enrichment are proposed for in-depth glycoproteomics
      research.

PMID- 22154984
TI  - Evaluation of bisphenol A glucuronidation according to UGT1A1*28 polymorphism by
      a new LC-MS/MS assay.
AB  - The endocrine disruptor bisphenol A (BPA) is a frequently used chemical in the
      manufacture of consumer products. In humans, BPA is extensively metabolized to
      BPA glucuronide (BPAG) by different UDP-glucuronosyltransferase (UGT) isoforms.
      The study has been performed with the intention to improve the accuracy of
      published physiologically based pharmacokinetic models and to improve regulatory
      risk assessments of BPA. In order to gain insight into intestine, kidney, liver,
      and lung glucuronidation of BPA, human microsomes of all tested organs were used.
      BPAG formation followed Michaelis-Menten kinetics in the intestine and kidney,
      but followed substrate inhibition kinetics in the liver. Human lung microsomes
      did not show glucuronidation activity towards BPA. While the liver intrinsic
      clearance was very high (857 mL min(-1)kg body weight(-1)), the tissue intrinsic
      clearances for the kidney and intestine were less than 1% of liver intrinsic
      clearance. Since BPA is a UGT1A1 substrate, we postulated that the common
      UGT1A1*28 polymorphism influences BPA glucuronidation, and consequently, BPA
      detoxification. Hepatic tissue intrinsic clearances for UGT1A1*1/*1,
      UGT1A1*1/*28, and UGT1A1*28/*28 microsomes were 1113, 1075, and 284 mL min(-1)kg
      body weight(-1), respectively. Prior to microsomal experiments, the bioproduction
      of BPAG and stable isotope-labeled BPAG (BPAG(d16)) was performed for the purpose
      of the reliable and accurate quantification of BPAG. In addition, a sensitive LC
      MS/MS analytical method for the simultaneous determination of BPA and BPAG based
      on two stable isotope-labeled internal standards was developed and validated. In
      conclusion, our in vitro results show that the liver is the main site of BPA
      glucuronidation (K(m) 8.9 MUM, V(max) 8.5 nmol min(-1) mg(-1)) and BPA metabolism
      may be significantly influenced by a person's genotype (K(m) 10.0-13.1 MUM,
      V(max) 3.4-16.2 nmol min(-1) mg(-1)). This discovery may be an important fact for
      the currently on-going worldwide BPA risk assessments and for the improvement of
      physiologically based pharmacokinetic models.

PMID- 22154985
TI  - The metabolism of steroids, toxins and drugs by 11beta-hydroxysteroid
      dehydrogenase 1.
AB  - 11beta-Hydroxysteroid dehydrogenase isoform 1 (11beta-HSD1) is a member of the
      alcohol short-chain family enzyme, and catalyzes the interconversion between
      active glucocorticoid cortisol (in human) and inactive cortisone. The redox ratio
      of NADP+/NADPH determines its direction with NADPH favoring its reductase
      activity and NADP+ favoring its oxidase activity. In many tissues such as the
      liver and lung, 11beta-HSD1 behaves primarily as a reductase because of the
      intracellular enzyme coupling with hexose-6-phosphate dehydrogenase, which uses
      the NADP+ as cofactor to supply NADPH driving 11beta-HSD1 to function as a
      reductase. 11beta-HSD1 catalyzes the metabolism of 7- or 11-keto steroids as well
      as many toxins and drugs. Some steroids, drugs and toxins are metabolically
      activated. The present review discusses the steroid, drug and toxin metabolism by
      11beta-HSD1.

PMID- 22154986
TI  - Cigarette smoke induces p-benzoquinone-albumin adduct in blood serum:
      Implications on structure and ligand binding properties.
AB  - Earlier we had reported that irrespective of the source cigarette smoke (CS)
      contains substantial amounts of p-benzosemiquinone, which is readily converted to
      p-benzoquinone (p-BQ) by disproportionation and oxidation by transition metal
      containing proteins. Here we show that after CS-exposure, p-BQ-protein adducts
      are formed in the lungs as well as serum albumin of guinea pigs. We also show
      that serum of human smokers contains p-BQ-albumin adduct. It is known that human
      serum albumin (HSA) plays a very important role in binding and transport of a
      variety of ligands, including fatty acids and drugs. We show in vitro that p-BQ
      forms covalent adducts with free amino groups of all twenty amino acids as well
      as E-amino groups of lysine residues of HSA in a concentration dependent manner.
      When HSA is incubated with p-BQ in the molar ratio of 1:1, the number of p-BQ
      incorporated is 1. At the molar ratio of 1:60, the number of p-BQ incorporated is
      40. The formation of HSA-p-BQ adduct has been demonstrated by absorption
      spectroscopy, MALDI-MS and MALDI-TOF-TOF-MS analyses. Upon complexation with p
      BQ, the secondary structure and conformation of HSA are altered, as evidenced by
      steady state and time-resolved fluorescence, circular dichroism, 8-anilino-1
      napthalenesulfonic acid binding and differential scanning calorimetry. Alteration
      of the structure and conformation of HSA results in impairment of its ligand
      binding properties with respect to myristic acid, quercitin and paracetamol. This
      might be one of the reasons why transport and distribution of lipids and drugs
      are impaired in smokers.

PMID- 22154987
TI  - Comparison of aerobic exercise, diet or both on lipids and lipoproteins in
      adults: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Given that previous studies have reached conflicting conclusions
      regarding the effects of diet (D), aerobic exercise (E) or both (DE) on blood
      lipid and lipoprotein concentrations in adults, the meta-analytic approach was
      used to address this issue. DATA SOURCES: Nine electronic databases, cross
      referencing, and expert review. STUDY SELECTION: Randomized controlled trials >=
      4 weeks that included a D, E, DE and control (C) group in adults >= 18 years of
      age and in which data for one or more of the following were available: total
      cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), triglycerides (TG). DATA EXTRACTION: Dual data
      extraction by the first two authors. STATISTICAL ANALYSIS: Random-effects models
      as well as mixed-effects models for between-group differences. RESULTS: Seven
      hundred and eighty-eight men and women from 6 studies were included. Non
      overlapping 95% confidence intervals were observed for D and DE with respect to
      lowering TC, LDL-C and TG while reductions in E were limited to TG. No
      significant changes in HDL-C were observed. When compared to E, reductions in TC
      and LDL-C were greater for D and DE (p < 0.05 for all). CONCLUSIONS: Diet,
      especially DE, are superior to E for improving selected lipids and lipoproteins
      in adults.

PMID- 22154988
TI  - Ferulic acid is nephrodamaging while gallic acid is renal protective in long term
      treatment of chronic kidney disease.
AB  - BACKGROUNDS & AIMS: The long term therapeutic effect of ferulic acid (FA) and
      gallic acid (GA) in treatment of chronic kidney disease (CKD) has been lacking.
      METHODS: Doxorubicin (DR, Adriamycin)-induced CKD rat model was established for
      this study. RESULTS: DR significantly reduced levels of serum albumin, GOT, GPT,
      RBC, TNF-alpha, and urinary creatinine and elevated serum cholesterol, TG, BUN,
      creatinine, uric acid, WBC, platelet count, and IL-6. In DRCKD rats, FA and GA
      significantly increased kidney weight and glomerular volume. FA reduced
      glomerular filtration rate but GA did not. FA enhanced more collagen deposition
      than GA in renal cortex and glomeruli. Both FA and GA showed crucial
      hyperlipidemic activity. The inhibitory effects of FA and GA on MMP-2 were very
      comparable. GA suppressed MMP-2 more effectively than FA in DRCKD rats. Both FA
      and GA induced SOD elevation and MDA elimination. In DRCKD rats, Western blot
      analysis indicated that FA further up-regulated CD34, alpha-SMA, tissue pDGFR, p
      PDGFR, and TGF-beta; and down-regulated p-PI3K, and p-Akt. Since both PDGF-BB and
      TGF-beta are considered to induce kidney prefibrosis stage, GA was proved to be
      more beneficial in this regard. CONCLUSIONS: GA tends to protect the CKD while FA
      is not recommended for the long term CKD therapy.

PMID- 22154990
TI  - Through with the looking glass: escape responses to implicit mirror exposure.
AB  - Based on the assumption that confrontation with one's physical reflection can be
      aversive, we explored the appeal of possible "escape routes" when incidentally
      exposed to one's mirror image. Compared to their no-exposure peers, individuals
      who felt less chronically "trapped" in their bodies showed increased interest in
      flow experiences and decreased interest in experiences involving low-level
      thinking or a subjective sense of meaning when exposed to their reflection.
      Mirror exposure also increased overall interest in "pure consciousness events,"
      wherein the transcendence of space and time figures centrally. The aversive
      effects of even implicit confrontation with one's reflection therefore seem more
      diverse than anticipated based on existing frameworks such as Objective Self
      Awareness theory, so additional theoretical development seems warranted.

PMID- 22154991
TI  - Clinical manifestations of a cluster of rotavirus infection in young infants
      hospitalized in neonatal care units.
AB  - PURPOSE: To define the clinical manifestations of rotavirus (RV) infection in
      neonates and young infants hospitalized in neonatal care units, which are rarely
      reported. MATERIALS AND METHODS: From October 2008 to September 2010, a total of
      153 stool specimens positive for RV were detected from 100 neonates and young
      infants hospitalized in neonatal care units of our hospital. Four infants had two
      episodes of RV infection. Demographics and clinical presentations of these
      infants were collected and analyzed. The infants were further classified as
      having hospital-acquired (HA) or community-acquired (CA) RV infection. RESULTS:
      Of the 104 episodes from 100 patients, 76 (73%) were classified as HA. Fifty-six
      infants were male. The mean age of onset was 2 days. The most common
      presentations were loose stool passages (52.9%), abdominal distension (51.9%),
      blood or mucus in stool (42.3%), and unstable vital signs (32.7%). Watery
      character in stool passage was identified in 13.5% of the infants and vomiting in
      21.2%. A picture suggestive of necrotizing enterocolitis (NEC) was identified in
      22 episodes (21.1%), and 12 of these were stage II or above. The average number
      of hospitalization days from the onset of HA-RV infection was 23 days. Compared
      with those in the CA group, the infants in the HA group had a significantly
      higher rate of blood or mucus in stools (52.6% vs. 14.3%, p < 0.01) and unstable
      vital signs (39.5% vs. 14.3%, p = 0.02), but a lower rate of watery diarrhea
      (9.2% vs. 28.6%, p = 0.04) and fever (13.8% vs. 42.9%, p < 0.01). Overall, there
      were five deaths, but all of these infants had major diseases. CONCLUSION:
      Bloody, mucoid stools and unstable vital signs, instead of fever with watery
      diarrhea, are commonly seen in neonates and young infants with RV infection. A
      substantial proportion of these infants may present as NEC. Once introduced, RV
      appears to become a troublesome problem of HA infections in neonatal care
      settings.

PMID- 22154989
TI  - Role of the pre- and post-natal environment in developmental programming of
      health and productivity.
AB  - The concept that developmental insults (for example, poor pre- or postnatal
      nutrition) can have long-term consequences on health and well-being of the
      offspring has been termed developmental programming. In livestock, developmental
      programming affects production traits, including growth, body composition, and
      reproduction. Although low birth weight was used as a proxy for compromised fetal
      development in the initial epidemiological studies, based on controlled studies
      using livestock and other animal models in the last two decades we now know that
      developmental programming can occur independently of any effects on birth weight.
      Studies in humans, rodents, and livestock also have confirmed the critical role
      of the placenta in developmental programming. In addition, the central role of
      epigenetic regulation in developmental programming has been confirmed. Lastly,
      relatively simple therapeutic/management strategies designed to 'rescue'
      placental development and function are being developed to minimize the effects of
      developmental programming on health and productivity of humans, livestock, and
      other mammals.

PMID- 22154992
TI  - Corynebacterium striatum bacteremia associated with central venous catheter
      infection.
AB  - Corynebacterium striatum (C striatum) has been considered a contaminant of blood
      culture in past decades. Here we report the case of a patient with acute
      deterioration of chronic renal failure. She received hemodialysis and died from C
      striatum bacteremia. By using a randomly amplified polymorphic DNA (RAPD) method,
      we found that an association existed between C striatum from the bloodstream and
      that from the central venous catheter. We suggest that C striatum could be a
      pathogen of bloodstream infection in patients with such a catheter in place.

PMID- 22154993
TI  - A review of immunomodulators in the Indian traditional health care system.
AB  - Some of the medicinal plants valued in Ayurvedic Rasayana for their therapeutic
      potential have been scientifically investigated with promising results. A number
      of plant-based principles have been isolated with potential immunomodulatory
      activity that can explain and justify their use in traditional medicine in the
      past and can form the basis for further research in the future as well. The aim
      of this review is to highlight results of research done on immunomodulators of
      plant origin. The selection of papers was made using the most relevant databases
      for the biomedical sciences on the basis of their ethnopharmacological use. Many
      plants and some phytoconstituents responsible for immunomodulation have been
      explained. The review also discusses biological screening methods for various
      plant drugs that focus on revealing the mechanism involved in immunomodulation.
      This work shall hopefully encourage researchers to undertake further work on
      medicinal plants with potential immunomodulatory activity.

PMID- 22154994
TI  - Outcomes and characteristics of ertapenem-nonsusceptible Klebsiella pneumoniae
      bacteremia at a university hospital in Northern Taiwan: a matched case-control
      study.
AB  - BACKGROUND AND PURPOSE: Carbapenem-resistant Klebsiella pneumoniae is an emerging
      problem worldwide. The object of this study was to investigate the risk factors,
      characteristics and outcomes of ertapenem-nonsusceptible K pneumoniae (ENSKp)
      bacteremia. METHODS: We conducted a 1:2 ratio matched case-control study. The
      controls were randomly selected among patients with ertapenem-susceptible K
      pneumoniae (ESKp) bacteremia and were matched with ENSKp cases for bacteremia.
      RESULTS: Seventy-five patients were included in this study (25 cases and 50
      controls). Bivariate analysis showed that prior exposure to either beta
      Lactam/beta-Lactam-lactamase inhibitors (p = 0.008) or 4(th) generation
      cephalosporins (p < 0.001), chronic obstructive pulmonary disease (COPD) (p =
      0.001), acute renal failure (p = 0.021), chronic kidney disease without dialysis
      (p = 0.021), recent hospital stay (p = 0.016), intensive care unit stay (p =
      0.002), mechanical ventilation (p = 0.003), central venous catheter placement (p
      = 0.016), Foley indwelling (p = 0.022), polymicrobial bacteremia (p = 0.003) and
      higher Pittsburgh bacteremia score (p < 0.001) were associated with ENSKp
      bacteremia. The multivariate analysis showed that prior exposure to 4(th)
      generation cephalosporins (odds ratio [OR], 28.05; 95% confidence interval [CI],
      2.92-269.85; p = 0.004), COPD (OR, 21.38; 95% CI, 2.95-154.92; p = 0.002) and
      higher Pittsburgh bacteremia score (OR, 1.35; 95% CI, 1.10-1.66; p = 0.004) were
      independent factors for ENSKp bacteremia. ENSKp bacteremia had a higher 14-day
      mortality rate than ESKp bacteremia (44.0% vs. 22.0%; p = 0.049). The overall in
      hospital mortality rates for these two groups were 60.0% and 40.0% respectively
      (p = 0.102). CONCLUSION: ENSKp bacteremia had a poor outcome and the risk factors
      were prior exposure of 4(th) generation cephalosporins, COPD and higher
      Pittsburgh bacteremia score. Antibiotic stewardship may be the solution for the
      preventive strategy.

PMID- 22154995
TI  - Protein enrichment, cellulase production and in vitro digestion improvement of
      pangolagrass with solid state fermentation.
AB  - BACKGROUND AND PURPOSE: Pangolagrass, Digitaria decumbens Stent, is a major grass
      for cow feeding, and may be a good substrate for protein enrichment. To improve
      the quality of pangolagrass for animal feeding, cellulolytic microbes were
      isolated from various sources and cultivated with solid state fermentation to
      enhance the protein content, cellulase production and in vitro digestion. The
      microbes, culture conditions and culture media were studied. METHODS:
      Cellulolytic microbes were isolated from pangolagrass and its extracts, and
      composts. Pangolagrass supplemented with nitrogen and minerals was used to
      cultivate the cellulolytic microbes with solid state fermentation. The optimal
      conditions for protein enrichment and cellulase activity were pangolagrass
      substrate at initial moisture 65-70%, initial pH 6.0-8.0, supplementation with
      2.5% (NH(4))(2)SO(4), 2.5% KH(2)PO(4) and K(2)HPO(4) mixture (2:1, w/w) and 0.3%
      MgSO(4).7H(2)O and cultivated at 30(o)C for 6 days. RESULTS: The protein content
      of fermented pangolagrass increased from 5.97-6.28% to 7.09-16.96% and the in
      vitro digestion improved from 4.11-4.38% to 6.08-19.89% with the inoculation of
      cellulolytic microbes by solid state fermentation. Each 1 g of dried substrate
      yielded Avicelase 0.93-3.76 U, carboxymethylcellulase 1.39-4.98 U and beta
      glucosidase 1.20-6.01 U. The isolate Myceliophthora lutea CL3 was the strain
      found to be the best at improving the quality of pangolagrass for animal feeding
      with solid state fermentation. CONCLUSION: Solid state fermentation of
      pangolagrass inoculated with appropriate microbes is a feasible process to enrich
      protein content, increase in vitro digestibility and improve the quality for
      animal feeding.

PMID- 22154996
TI  - Lemierre syndrome complicating multiple brain abscesses caused by extended
      spectrum beta-lactamase-producing Klebsiella pneumoniae cured by fosfomycin and
      meropenem combination therapy.
AB  - A woman aged 56 years of age had a community-acquired left neck abscess and
      internal jugular vein thrombosis with septicemia due to extended-spectrum beta
      lactamase (ESBL)-producing Klebsiella pneumoniae. Even though she was treated
      with intravenous meropenem, the bacteremia persisted. She was complicated with
      multiple brain abscesses, seizure, and leucopenia. After a combination of
      intravenous fosfomycin and meropenem, her clinical condition became stable.
      Combination treatment was continued for 2 months and she recovered. In individual
      cases of Lemierre syndrome with brain abscess caused by ESBL-producing
      Enterobacteriaceae, fosfomycin combination therapy may be the alternative choice.

PMID- 22154997
TI  - Seroprevalence of enterovirus 71 and no evidence of crossprotection of
      enterovirus 71 antibody against the other enteroviruses in kindergarten children
      in Taipei city.
AB  - BACKGROUND/PURPOSE: Enterovirus 71 (EV71) infection may cause severe neurological
      and cardiopulmonary complications, especially in preschool children. This study
      is to investigate the seroprevalence and seroconversion of EV71, and the
      crossprotection of EV71 antibody against other enteroviruses among
      kindergarteners. METHODS: Overall 228 children in a public kindergarten were
      enrolled during two academic years, 2006 and 2007, in Taipei, Taiwan and we
      measured their EV71 neutralizing antibody. When the participants had herpangina;
      hand, foot and mouth disease (HFMD); febrile illness or respiratory symptoms,
      throat swabs were sampled and processed for viral culture and enterovirus real
      time reverse transcriptase polymerase chain reaction (RT-PCR). Questionnaires,
      completed by the participants' guardians, surveyed the history of allergy and
      annual incidence of symptoms related to enterovirus infection. RESULTS:
      Seropositive rates of EV71 were 20% (32/163) in 2006 and 6% (4/65) in 2007. The
      rate of EV71 seropositivity increased with age (p < 0.01) in 2006 but it did not
      differ between genders (p = 0.14). No seroconversion was observed from 2006 to
      2007. Herpangina occurred in 64% of children with EV71 seropositivity and 48% of
      those without EV71 antibodies (p = 0.12). Non-71 enterovirus infection, confirmed
      by viral study, occurred in 53% (19/36) of the EV71-seropositive children and in
      53% (102/192) of EV71-seronegative children (p = 0.89). No participants had EV71
      infection during the study period. CONCLUSION: EV71 did not frequently circulate
      in Taipei City from September 2006 to June 2008. Presence of EV71 neutralizing
      antibody was not associated with lower incidence of enterovirus infection caused
      by non-71 serotypes.

PMID- 22154998
TI  - Successful treatment of Aerococcus viridans endocarditis in a patient allergic to
      penicillin.
AB  - Aerococcus viridans is a rare human pathogen that occasionally causes
      endocarditis. Most of the reported cases of endocarditis have been treated with
      penicillin. Here we describe a patient who was allergic to penicillin and was
      successfully treated with cefotaxime.

PMID- 22154999
TI  - The first homolog of pacifastin-related precursor in the swimming crab (Portunus
      trituberculatus): characterization and potential role in immune response to
      bacteria and fungi.
AB  - Among all the serine proteinase inhibitor families (SPIs), the pacifastin-related
      inhibitor is seldom isolated. A pacifastin-related SPI named as PtPLC was
      identified from the swimming crab Portunus trituberculatus in this study. The
      full-length of PtPLC was cloned from haemocytes cDNA library by the combination
      of homology cloning and rapid amplification of cDNA ends (RACE). The PtPLC
      contained an open reading frame (ORF) of 1098 bp encoding a putative pacifastin
      related precursor of 365 amino acids, a 5'-untranslated region (UTR) of 33 bp,
      and a 3'-UTR of 524 bp. The estimated molecular weight of mature PtPLC was 40.51
      kDa and its isoelectric point was 5.04. Eight PLD domains in PtPLC shared a
      common characteristic of conserved array of six cysteine residues (Cys-Xaa(9-12)
      Cys-Asn-Xaa-Cys-Xaa- Cys-Xaa(2-3)-Gly-Xaa(3-4)-Cys-Thr-Xaa(3)-Cys). The mRNA
      expression of PtPLC transcripts was highly detected in haemocytes, gill,
      hepatopancreas and stomach. The temporal expression levels of PtPLC transcripts
      in haemocytes showed different expression patterns after challenged by Gram
      negative bacteria Vibrio alginolyticus, Gram-positive bacteria Micrococcus luteus
      and fungus Pichia pastoris. There were two peaks in the mRNA expression profile
      after M. luteus stimulation. And after V. alginolyticus and P. pastoris
      stimulation, there were three peaks in the mRNA expression profiles. These
      findings suggest that PtPLC is involved in the antibacterial defense mechanism of
      P. tritubercualtus.

PMID- 22155000
TI  - A soluble epoxide hydrolase inhibitor--8-HUDE increases pulmonary
      vasoconstriction through inhibition of K(ATP) channels.
AB  - Epoxyeicosatrienoic acids (EETs), cytochrome P450-derived metabolites of
      arachidonic acid, are endogenously produced epoxides that act as substrates for
      the soluble epoxide hydrolase (sEH). Recent studies indicate that EETs increase
      the tension of rat pulmonary arteries (PAs), and inhibition of sEH augments
      hypoxic pulmonary vasoconstriction. However, the mechanisms underlying the
      proconstrictive effects of sEH inhibitors in pulmonary artery smooth muscle cells
      (PASMCs) are unclear. In the present study, we used a sEH inhibitor, 12-(3
      hexylureido) dodec-8-enoic acid (8-HUDE), to examine the ionic mechanisms
      underlying the constriction of PAs. 8-HUDE increased the tension of rat PAs to
      145% baseline in a manner which was effectively eliminated by 10 MUmol/L
      glibenclamide, an inhibitor of ATP-sensitive K(+) (K(ATP)) channels. Whole cell
      currents of HEK cells transfected with Kir6.1 or SUR2B were activated by K(ATP)
      channel opener pinacidil, inhibited by K(ATP) channel inhibitor glibenclamide or
      inhibited by 8-HUDE in a concentration-dependent manner with an IC50 value of 40
      uM. In addition, 8-HUDE inhibited the expression of Kir6.1 and SUR2B at both mRNA
      and protein level in rat PASMCs. These observations suggest that 8-HUDE exerts
      acute effects on K(ATP) channel activity as well as subacute effects through
      decreased channel expression, and these effects are, at least in part, via the
      Kir6.1/SUR2B channel.

PMID- 22155001
TI  - Long-term omalizumab treatment in severe allergic asthma: the South-Eastern
      Mediterranean "real-life" experience.
AB  - BACKGROUND: Omalizumab is a recombinant humanized anti-IgE monoclonal antibody
      indicated as an add-on treatment for severe allergic asthma, inadequately
      controlled despite high dose of inhaled corticosteroids (ICS) and long-acting b2
      agonists. OBJECTIVES: Medical registries were used to evaluate the 4 months, 1
      and 4 years effectiveness of omalizumab treatment, in a non-interventional,
      observational "real-life" study. METHODS: Sixty patients with severe persistent
      allergic asthma from 5 South-Eastern Mediterranean centres from Crete and Cyprus
      were evaluated. Effectiveness outcomes included spirometry, severe asthma
      exacerbations rate, level of asthma control (ACT), and additional asthma
      medication (inhaled steroids). RESULTS: Outcome variables improved after 4 months
      and sustained after 1 and 4 years treatment with Omalizumab. FEV1 improved
      statistically significant at all time points versus baseline [DeltaFEV1 (% pred.)
      = +21 p = 0.008 at 4 months, DeltaFEV1 (% pred.) = +24.5 p < 0.0001 at 4 years
      after treatment]. Similarly, FVC increased statistically significant versus
      baseline [DeltaFVC (% pred.) = +20 p = 0.002 at 4 months, DeltaFVC (% pred.) =
      +22.6 p = 0.0002 at 4 years]. The level of asthma control as evaluated by ACT was
      significantly improved after treatment (+12% p = 0.001 at 4 months, +24% p <
      0.0001 at 4 years). Omalizumab treatment reduced significantly asthma
      exacerbations rate (-65% p = 0.0002 at 1 year, and -70% p < 0.0001 at 4 years).
      The use of inhaled steroids decreased statistically significant after 4 months (p
      = 0.017), 1 year (p = 0.029) and 4 years (p = 0.014) of omalizumab treatment.
      CONCLUSIONS: This long-term "real-life" study demonstrated significant
      improvement in lung function and other clinical outcomes after omalizumab
      treatment, evident at 4 months, and sustained after 1 and 4 years suggesting its
      efficacy in severe allergic asthma, in the "real-life" practice.

PMID- 22155002
TI  - Impaired myelination of the human hippocampal formation in Down syndrome.
AB  - Myelination is considered as one of the last steps of neuronal development and is
      essential to the physiologically matured function of afferent and efferent
      pathways. In the present study, myelin formation was examined in the human fetal,
      postnatal and adult hippocampal formation in Down syndrome and in age-matched
      controls with immunohistochemistry detecting a protein component of the myelin
      sheath, the myelin basic protein synthesized by oligodendroglial cells.
      Myelination is mainly a postnatal event in the hippocampal formation of both
      healthy controls and in patients with Down syndrome. In patients with Down
      syndrome the sequence of myelination of the hippocampal formation followed a
      similar developmental pattern to that in controls. However, myelin formation was
      generally delayed in Down syndrome compared to age-matched controls. In addition,
      in the hilus of the dentate gyrus a decreased density of myelinated axons was
      detected from the start of myelination until adulthood. The majority of local
      axons (mossy fibers) are not myelinated in the hilar region and myelinated fibers
      arriving in the hilus come mainly from the subcortical septal nuclei. Since
      intact septo-hippocampal connections are necessary for memory formation, we
      hypothesize that decreased myelination in the hilus may contribute to the mental
      retardation of Down syndrome patients.

PMID- 22155003
TI  - The molecular basis for inhibition of sulindac and its metabolites towards human
      aldose reductase.
AB  - Sulindac (SLD) exhibits both the highest inhibitory activity towards human aldose
      reductase (AR) among popular non-steroidal anti-inflammatory drugs and clear
      beneficial clinical effects on Type 2 diabetes. However, the molecular basis for
      these properties is unclear. Here, we report that SLD and its pharmacologically
      active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective
      as un-competitive inhibitors of AR in vitro. Crystallographic analysis reveals
      that pi-pi stacking favored by the distinct scaffold of SLDs is pivotal to their
      high AR inhibitory activities. These results also suggest that SLD sulfone could
      be a potent lead compound for AR inhibition in vivo.

PMID- 22155004
TI  - D-Lactate dehydrogenase as a marker gene allows positive selection of transgenic
      plants.
AB  - D-Lactate negatively affects Arabidopsis thaliana seedling development in a
      concentration-dependent manner. At media D-lactate concentrations greater than 5
      10mM the development of wild-type plants is arrested shortly after germination
      whereas plants overexpressing the endogenous D-lactate dehydrogenase (D-LDH)
      detoxify D-lactate to pyruvate and survive. When the transgenic plants are
      further transferred to normal growth conditions they develop indistinguishably
      from the wild type. Thus, D-LDH was successfully established as a new marker in
      A. thaliana allowing selecting transgenic plants shortly after germination. The
      selection on D-lactate containing media adds a new optional marker system, which
      is especially useful if the simultaneous selection of multiple constructs is
      desired.

PMID- 22155006
TI  - Reduced cardiac CapZ protein protects hearts against acute ischemia-reperfusion
      injury and enhances preconditioning.
AB  - The Z-disc protein CapZ has historically been classified as a structural element,
      anchoring sarcomeric actin. Our previous work expanded its role to include signal
      transduction, as CapZ transgenic myofilaments are less sensitive to protein
      kinase C (PKC). Myocardial PKC has paradoxical effects, mediating both
      preconditioning and ischemia-reperfusion (IR) injury. Our objective was to
      determine how decreased CapZ affects IR injury and cardiac preconditioning. Mouse
      hearts were subjected to 20 min global ischemia and 60 min reperfusion. Some
      hearts were preconditioned with intermittent IR (IPC). Left ventricular function
      was assessed and myocardial tissue collected post-IR for molecular analysis and
      tissue staining. Post-ischemic function was significantly better and infarct size
      smaller in CapZ transgenic hearts, as compared to wildtype. IPC decreased IR
      damage in both wildtype and CapZ transgenic hearts, although CapZ transgenic
      hearts performed significantly better than wildtype. Immunoblotting revealed
      increased myofilament-associated PKC-alpha and -epsilon following IR in wildtype
      hearts, but no change in PKC-delta or -zeta. By contrast, post-IR myofilament
      associated PKC-alpha was significantly higher in CapZ transgenic mice but the
      rise in PKC-epsilon was attenuated. Both PKC-delta and PKC-zeta decreased in CapZ
      transgenic myofilaments following IR. IPC increased myofilament-associated PKC
      alpha and -epsilon, while decreasing PKC-delta in wildtype hearts. Preconditioned
      CapZ IPC hearts showed attenuated increases in myofilament PKC-alpha and 
      epsilon, but also a significant decrease in myofilament PKC-delta and -zeta.
      These data demonstrate significant differences in post-IR myofilament PKC in
      untreated and preconditioned CapZ transgenic mice. CapZ reduction did not
      dramatically affect post-IR myofilament function, nor did preconditioning. These
      results demonstrate that CapZ deficiency decreases IR injury, while providing
      enhanced cardioprotection with IPC. The cardioprotected phenotype of CapZ
      transgenic mice is associated with an altered translocation of PKC-isoforms to
      cardiac myofilaments.

PMID- 22155007
TI  - No evidence for behavioral responses to circularly polarized light in four scarab
      beetle species with circularly polarizing exocuticle.
AB  - The strongest known circular polarization of biotic origin is the left-circularly
      polarized (LCP) light reflected from the metallic shiny exocuticle of certain
      beetles of the family Scarabaeidae. This phenomenon has been discovered by
      Michelson in 1911. Although since 1955 it has been known that the human eye
      perceives a visual illusion when stimulated by circularly polarized (CP) light,
      it was discovered only recently that a stomatopod shrimp is able to perceive
      circular polarization. It is pertinent to suppose that scarab beetles reflecting
      LCP light in an optical environment (vegetation) being deficient in CP signals
      may also perceive circular polarization and use it to find each other
      (mate/conspecifics) as until now it has been believed. We tested this hypothesis
      in six choice experiments with several hundred individuals of four scarab
      species: Anomala dubia, Anomala vitis (Coleoptera, Scarabaeidae, Rutelinae), and
      Cetonia aurata, Potosia cuprea (Coleoptera, Scarabaeidae, Cetoniinae), all
      possessing left-circularly polarizing exocuticle. From the results of our
      experiments we conclude that the studied four scarab species are not attracted to
      CP light when feeding or looking for mate or conspecifics. We demonstrated that
      the light reflected by host plants of the investigated scarabs is circularly
      unpolarized. Our results finally solve a puzzle raised over one hundred years
      ago, when Michaelson discovered that scarab beetles reflect circularly polarized
      light.

PMID- 22155005
TI  - Enhanced desumoylation in murine hearts by overexpressed SENP2 leads to
      congenital heart defects and cardiac dysfunction.
AB  - Sumoylation is a posttranslational modification implicated in a variety of
      cellular activities, and its role in a number of human pathogeneses such as cleft
      lip/palate has been well documented. However, the importance of the SUMO
      conjugation pathway in cardiac development and functional disorders is newly
      emerging. We previously reported that knockout of SUMO-1 in mice led to
      congenital heart diseases (CHDs). To further investigate the effects of
      imbalanced SUMO conjugation on heart development and function and its underlying
      mechanisms, we generated transgenic (Tg) mice with cardiac-specific expression of
      SENP2, a SUMO-specific protease that deconjugates sumoylated proteins, to
      evaluate the impact of desumoylation on heart development and function.
      Overexpression of SENP2 resulted in premature death of mice with CHDs-atrial
      septal defects (ASDs) and/or ventricular septal defects (VSDs).
      Immunobiochemistry revealed diminished cardiomyocyte proliferation in SENP2-Tg
      mouse hearts compared with that in wild type (WT) hearts. Surviving SENP2-Tg mice
      showed growth retardation, and developed cardiomyopathy with impaired cardiac
      function with aging. Cardiac-specific overexpression of the SUMO-1 transgene
      reduced the incidence of cardiac structural phenotypes in the sumoylation
      defective mice. Moreover, cardiac overexpression of SENP2 in the mice with Nkx2.5
      haploinsufficiency promoted embryonic lethality and severity of CHDs, indicating
      the functional interaction between SENP2 and Nkx2.5 in vivo. Our findings
      indicate the indispensability of a balanced SUMO pathway for proper cardiac
      development and function. This article is part of a Special Issue entitled 'Post
      translational Modification SI'.

PMID- 22155008
TI  - Neurological and stress related effects of shifting obese rats from a palatable
      diet to chow and lean rats from chow to a palatable diet.
AB  - Rats exposed to an energy rich, cafeteria diet overeat and become obese. The
      present experiment examined the neural and behavioural effects of shifting obese
      rats from this diet to chow and lean rats from chow to the cafeteria diet. Two
      groups of male Sprague Dawley rats (n=24) were fed either highly palatable
      cafeteria diet or regular chow (30% vs. 12% energy as fat) for 16 weeks. Half of
      each group (n=12) was then switched to the opposing diet while the remainder
      continued on their original diet. The effects of diet switch on the response to
      restraint stress were assessed and rats were euthanised nine days after diet
      reversal. After 16 weeks of cafeteria diet, rats were 27% heavier than controls.
      Rats switched from chow to cafeteria diet (Ch-Caf) became hyperphagic and had
      increased dopamine D1, D2 and tyrosine hydroxylase mRNA expression in the ventral
      tegmental area (VTA) compared to rats switched from cafeteria to chow (Caf-Ch).
      Caf-Ch rats were hypophagic with significant reductions in white (16%) and brown
      (32%) adipose tissue mass, plasma leptin (34%) and fasting glucose (22%) compared
      to rats remaining on the cafeteria diet (Caf-Caf). Caf-Caf rats had an elevated
      plasma corticosterone response to restraint stress compared to Ch-Caf rats
      indicating that acute but not chronic consumption of palatable cafeteria diet may
      protect against stress. Caf-Ch rats had increased corticotropin releasing hormone
      mRNA expression in the dorsal hypothalamus compared to Ch-Ch rats implying that
      removal of the palatable diet activated the HPA axis. The results were discussed
      in terms of the links between palatability of diet, obesity and stress.

PMID- 22155009
TI  - Network structures and their relevance to the policy cycle: a case study of The
      National Male Health Policy of Australia.
AB  - While focussing on influential actors within a policy network may provide insight
      into the shaping of policy, it fails to elucidate how the network itself may
      moderate the behaviours of actors when participating in the policy process.
      Applying Skok's (1995) structural-functional framework, this study explores
      whether network analysis provides an alternative analytical approach to explain
      how the broader structural features of the network may influence actors
      participating in different functional phases of the policy cycle. To illustrate
      the rationale for a network analysis approach to policy analysis, we introduce
      the 2010 Australian National Male Health Policy, as an illustrative case of a
      network of competing interests within the broader health policy domain. An
      analysis of the associated men's health network and the network structures that
      exist for different relational purposes identified a weak (low density) network,
      which lacked a hierarchical structure, and where levels of reciprocity between
      actors was low. Network characteristics changed depending on the relationship
      type between actors, highlighting the dynamic nature of networks and reflecting
      the different imperatives of the policy process. An understanding of network
      structures gained from the network analysis approach described in this study
      potentially provides policy-makers, and stakeholders, with an alternative tool to
      stakeholder analysis when considering engagement with the policy process.

PMID- 22155010
TI  - Effect of Coriolus versicolor supplemented diet on innate immune response and
      disease resistance in kelp grouper Epinephelus bruneus against Listonella
      anguillarum.
AB  - The effect of Coriolus versicolor extract supplemented diets on innate immune
      response and disease resistance in kelp grouper, Epinephelus bruneus against
      Listonella anguillarum, is reported. Kelp grouper were divided into four groups
      of 25 each and fed with C. versicolor enriched diets at 0% (control), 0.01%,
      0.1%, and 1.0% level. After 30 days of feeding, all fish were injected
      interaperitoneally (i.p.) with 50 MUl of L. anguillarum (4.7 * 10(7) CFU) to
      investigate the immune parameters at weeks 1, 2, and 4. The reactive oxygen
      species and reactive nitrogen species production were significantly enhanced in
      fish fed with 0.1% and 1.0% supplementation diets from weeks 1-4 when compared to
      the non enriched diet fed and infected control. The phagocytic activity
      significantly increased with 0.1% and 1.0% diets on weeks 2 and 4. The leucocyte
      myeloperoxidase content, lysozyme activity, and total protein level significantly
      increased when fed with 0.1% and 1.0% supplementation diets from weeks 1-4. The
      cumulative mortality was 35% and 45% in 1.0% and 0.1% enriched diet fed groups
      whereas it was 55% and 80% in 0.01% and 0% groups respectively. The present
      results suggest that diets enriched with C. versicolor at 0.1% or 1.0% level
      positively enhance the innate immune system and affords protection from L.
      anguillarum.

PMID- 22155011
TI  - Induction of anti-viral genes during acute infection with Viral hemorrhagic
      septicemia virus (VHSV) genogroup IVa in Pacific herring (Clupea pallasii).
AB  - Infection with the aquatic rhabdovirus Viral hemorrhagic septicemia virus (VHSV)
      genogroup IVa results in high mortality in Pacific herring (Clupea pallasii) and
      is hypothesized to be a potential limiting factor for herring recovery. To
      investigate anti-viral immunity in the Pacific herring, four immune response
      genes were identified: the myxovirus resistance (Clpa-Mx), a major
      histocompatibility complex IB (named Clpa-UAA.001), the inducible
      immunoproteosome subunit 9 (Clpa-PSMB9) and the neutrophil chemotactic factor
      (Clpa-LECT2). Reverse transcriptase quantitative PCR (RT-qPCR) assays were
      developed based on these gene sequences to investigate the host immune response
      to acute VHSV infection following both injection and immersion challenge. Virus
      levels were measured by both plaque assay and RT-qPCR and peaked at day 6 during
      the 10-day exposure period for both groups of fish. The interferon stimulated
      genes (Clpa-Mx, -UAA.001, and -PSMB9) were significantly up-regulated in response
      to VHSV infection at both 6 and 10 days post-infection in both spleen and fin.
      Results from this study indicate that Pacific herring mount a robust, early
      antiviral response in both fin and spleen tissues. The immunological tools
      developed in this study will be useful for future studies to investigate
      antiviral immunity in Pacific herring.

PMID- 22155012
TI  - A reliable technique for securing grafts in paediatric hand burns.

PMID- 22155013
TI  - Three novel single-nucleotide polymorphisms of complement component 4 gene (C4A)
      in Chinese Holstein cattle and their associations with milk performance traits
      and CH50.
AB  - Complement component 4 (C4A) is a candidate gene that reflects complement
      activity. The primary role of this gene in the classical and lectin-activation
      pathways is to provide protection against bacterial pathogens. In the current
      study, the bovine complement C4A gene was screened for polymorphisms, and the
      associations of these polymorphisms with the hemolytic activity of the classical
      pathway (CH50), C4 serum levels, and milk performance traits were examined. Three
      novel single-nucleotide polymorphisms (rs 132741478: g.2994 A>G, rs 134006517:
      g.3508 A>G, and rs 137485678: g.3649 G>C) were detected by DNA sequencing and PCR
      RFLP in 1182 Chinese Holstein cows. The rs 132741478: g.2994 A>G mutation in exon
      10 led to methionine and valine exchange at position 362, whereas rs 134006517:
      g.3508 A>G and rs 137485678: g.3649 G>C were synonymous substitutions. The
      statistical analyses revealed that cows with rs 132741478: g.2994 A>G-AG and rs
      137485678: g.3649 G>C-CC have significantly lower somatic cell scores (SCS,
      P<0.01). Homozygote cows with GAC haplotypes have the lowest SCS, whereas AAG/AAC
      cows have the highest. The serum concentration of C4 by ELISA and the hemolytic
      and antibacterial activity of CH50 were also evaluated in the current study. The
      results confirmed that rs 132741478: g.2994 A>G in the coding sequence of the
      beta-chain of the bovine C4A gene is related to mastitis resistance. This
      polymorphism may be very important in marker-assisted selections in dairy cattle
      breeding programs.

PMID- 22155014
TI  - Neurocognitive endophenotypes of impulsivity and compulsivity: towards
      dimensional psychiatry.
AB  - A key criticism of the main diagnostic tool in psychiatry, the Diagnostic and
      Statistical Manual of Mental Health Disorders (DSM-IV), is that it lacks a
      biological footing. In this article, we argue for a biological approach to
      psychiatry based on 'neurocognitive endophenotypes', whereby changes in
      behavioural or cognitive processes are associated with discrete deficits in
      defined neural systems. We focus on the constructs of impulsivity and
      compulsivity as key examples of the approach and discuss their possible cross
      diagnostic significance, applying them to co-morbidities and commonalities across
      a range of disorders (attention-deficit/hyperactivity disorder, substance
      dependence, obsessive-compulsive disorder and eating disorders). We argue that
      this approach has important implications for the future classification of
      psychiatric disorders, genetics and therapeutics.

PMID- 22155016
TI  - Autoantibodies in patients with chronic hepatitis C virus infection: pitfalls for
      the diagnosis of rheumatic diseases.
AB  - Hepatitis C virus infection (HCV) is one of the best mimes in medicine. About 40
      70% of patients suffering from this disorder develop at least one extra-hepatic
      disorder that can have a rheumatic nature (arthralgias, arthritis, vasculitis and
      sicca syndrome) and must be differentiated from the primitive rheumatic diseases.
      In addition, HCV infection can also alter the laboratory tests. Several
      alterations of first line laboratory tests can be usually found in both chronic
      HCV infection and chronic inflammatory rheumatic disorders. In the present review
      we analyze the interference of HCV in tests more specifically used in
      rheumatology: rheumatoid factor and other autoantibodies (ANA, anti-ENA, ANCA,
      anti-DNA, antiphospholipid, anti-CCP). In patients suffering from HCV infection,
      the diagnosis of connective tissue diseases (CTD) or rheumatoid arthritis (RA)
      should be made only when the detected symptoms or laboratory data are not
      inducible by HCV, otherwise only a diagnosis of "possible CTD" or "possible RA"
      should be considered.

PMID- 22155017
TI  - Agricultural biotechnology and smallholder farmers in developing countries.
AB  - Agricultural biotechnology holds much potential to contribute towards crop
      productivity gains and crop improvement for smallholder farmers in developing
      countries. Over 14 million smallholder farmers are already benefiting from
      biotech crops such as cotton and maize in China, India and other Asian, African
      and Central/South American countries. Molecular breeding can accelerate crop
      improvement timescales and enable greater use of diversity of gene sources.
      Little impact has been realized to date with fruits and vegetables because of
      development timescales for molecular breeding and development and regulatory
      costs and political considerations facing biotech crops in many countries.
      Constraints to the development and adoption of technology-based solutions to
      reduce yield gaps need to be overcome. Full integration with broader commercial
      considerations such as farmer access to seed distribution systems that facilitate
      dissemination of improved varieties and functioning markets for produce are
      critical for the benefits of agricultural biotechnology to be fully realized by
      smallholders. Public-private partnerships offer opportunities to catalyze new
      approaches and investment while accelerating integrated research and development
      and commercial supply chain-based solutions.

PMID- 22155015
TI  - Genes, tolerance and systemic autoimmunity.
AB  - The characterization of functional CD8(+) inhibitory or regulatory T cells and
      their gene regulation remains a critical challenge in the field of tolerance and
      autoimmunity. Investigating the genes induced in regulatory cells and the
      regulatory networks and pathways that underlie mechanisms of immune resistance
      and prevent apoptosis in the CD8(+) T cell compartment are crucial to
      understanding tolerance mechanisms in systemic autoimmunity. Little is currently
      known about the genetic control that governs the ability of CD8(+) Ti or
      regulatory cells to suppress anti-DNA Ab production in B cells. Silencing genes
      with siRNA or shRNA and overexpression of genes with lentiviral cDNA transduction
      are established approaches to identifying and understanding the function of
      candidate genes in tolerance and immunity. Elucidation of interactions between
      genes and proteins, and their synergistic effects in establishing cell-cell cross
      talk, including receptor modulation/antagonism, are essential for delineating the
      roles of these cells. In this review, we will examine recent reports which
      describe the modulation of cells from lupus prone mice or lupus patients to
      confer anti-inflammatory and protective gene expression and novel associated
      phenotypes. We will highlight recent findings on the role of selected genes
      induced by peptide tolerance in CD8(+) Ti.

PMID- 22155018
TI  - Solvent tolerance in Gram-negative bacteria.
AB  - Bacteria have been found in all niches explored on Earth, their ubiquity derives
      from their enormous metabolic diversity and their capacity to adapt to changes in
      the environment. Some bacterial strains are able to thrive in the presence of
      high concentrations of toxic organic chemicals, such as aromatic compounds,
      aliphatic alcohols and solvents. The extrusion of these toxic compounds from the
      cell to the external medium represents the most relevant aspect in the solvent
      tolerance of bacteria, however, solvent tolerance is a multifactorial process
      that involves a wide range of genetic and physiological changes to overcome
      solvent damage. These additional elements include reduced membrane
      permeabilization, implementation of a stress response programme, and in some
      cases degradation of the toxic compound. We discuss the recent advances in our
      understanding of the mechanisms involved in solvent tolerance.

PMID- 22155019
TI  - Quantitative second-harmonic generation microscopy for imaging porcine cortical
      bone: comparison to SEM and its potential to investigate age-related changes.
AB  - We propose the use of second-harmonic generation (SHG) microscopy for imaging
      collagen fibers in porcine femoral cortical bone. The technique is compared with
      scanning electron microscopy (SEM). SHG microscopy is shown to have excellent
      potential for bone imaging primarily due its intrinsic specificity to collagen
      fibers, which results in high contrast images without the need for specimen
      staining. Furthermore, this technique's ability to quantitatively assess collagen
      fiber organization is evaluated through an exploratory examination of bone
      structure as a function of age, from very young to mature bone. In particular,
      four different age groups: 1 month, 3.5 months, 6 months, and 30 months, were
      studied. Specifically, we employ the recently developed Fourier transform-second
      harmonic generation (FT-SHG) imaging technique for the quantification of the
      structural changes, and observe that as the bone develops, there is an overall
      reduction in porosity, the number of osteons increases, and the collagen fibers
      become comparatively more organized. It is also observed that the variations in
      structure across the whole cross-section of the bone increase with age. The
      results of this work show that quantitative SHG microscopy can serve as a
      valuable tool for evaluating the structural organization of collagen fibers in ex
      vivo bone studies.

PMID- 22155020
TI  - [Professional practices evaluation programme regarding patients operated of a hip
      fracture].

PMID- 22155022
TI  - Formation of membrane-defined compartments by tick-borne encephalitis virus
      contributes to the early delay in interferon signaling.
AB  - Interferons are key mediators of the innate antiviral response of the cell
      against viral infections. Viruses on the other hand have evolved various
      strategies to delay innate immunity in order to establish a productive infection.
      In this work we analyzed the pathway of interferon induction by the tick-borne
      encephalitis virus. We initially observed a consistent delay of interferon
      induction following virus replication. RIG-I, but not MDA5, and nuclear
      translocation of IRF3 were eventually required for interferon activation pointing
      to a defect in pattern recognition receptor's signaling. However, viral proteins
      could not directly inhibit the pathway suggesting an indirect mechanism. We found
      that dsRNA replication intermediates and replicated viral RNA localized to
      membrane-defined perinuclear compartments that resisted RNAse treatment. Thus,
      initial escape from innate immunity involved the formation of replication
      vesicles that may function as a barrier to pattern recognition receptors.

PMID- 22155023
TI  - Solid-state NMR analysis of steroidal conformation of 17alpha- and 17beta
      estradiol in the absence and presence of lipid environment.
AB  - Solid-state {(1)H}(13)C cross-polarization/magic angle spinning (CP/MAS) NMR
      spectroscopy has been applied to 17beta-estradiol (E2) and 17alpha-estradiol
      (E2alpha), to analyze the steroidal ring conformations of the two isomers in the
      absence and presence of lipids at the atomic level. In the absence of lipid, the
      high-resolution (13)C NMR signals of E2 in a powdered form show only singlet
      patterns, suggesting a single ring conformation. In contrast, the (13)C signals
      of E2alpha reveal multiplet patterns with splittings of 20-300Hz, implying
      multiple ring conformations. In the presence of a mimic of the lipid environment,
      made by mixing 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2
      diheptanoyl-sn-glycero-3-phosphocholine (DHPC) in a molar ratio 3:1, E2 and
      E2alpha revealed multiplet patterns different from those seen in the absence of
      lipids, indicating that the two isomers adopt multiple conformations in the lipid
      environment. In this work, on the basis of chemical shift isotropy and anisotropy
      analysis, we demonstrated that E2 and E2alpha prefer to adopt multiple steroidal
      ring conformations in the presence of a lipid environment, distinct from that
      observed in solution phase and powdered form.

PMID- 22155025
TI  - If you build a rare disease registry, will they enroll and will they use it?
      Methods and data from the National Registry of Myotonic Dystrophy (DM) and
      Facioscapulohumeral Muscular Dystrophy (FSHD).
AB  - INTRODUCTION: Registries are becoming increasingly important for rare diseases as
      experimental therapies develop. This report describes the methodology behind the
      National Registry of Myotonic Dystrophy (DM) and Facioscapulohumeral Muscular
      Dystrophy (FSHD) Patients and Family Members to facilitate the development of
      other rare disease registries. We also highlight data about the pathophysiology
      and select burdens of DM and FSHD reported at baseline and longitudinally.
      METHODS: The Registry consists of de-identified, patient reported information
      collected at baseline and annually and information from review of medical
      records. Investigators can use the Registry to analyze de-identified data and to
      facilitate recruitment into clinical studies. RESULTS: To date, the Registry has
      enrolled 1611 members, facilitated 24 studies, and collected data annually for up
      to 8 years. Genetic test results were obtained in 56.2% of enrollees.
      Approximately one-third of members used assistive devices and another one-third
      reported psychological problems at baseline. Wheelchair use was reported for both
      short and long distances by 7.0% of DM and 18.1% of FSHD members. Approximately
      60% of members reported their employment was affected by their disease.
      CONCLUSIONS: Strengths of the Registry include large sample sizes, stringent
      review of clinical and molecular data, annually updated information, and regular
      interactions between patients and investigators. Registry data provide new
      insights into the burdens of DM and FSHD, such as, psychological problems and
      reduced employment. Opportunities abound for investigators to utilize Registry
      resources to assess the impact of these and other burdens on health care costs,
      progression of symptoms, and quality of life.

PMID- 22155026
TI  - Structural modelling and dynamics of proteins for insights into drug
      interactions.
AB  - Proteins are the workhorses of biomolecules and their function is affected by
      their structure and their structural rearrangements during ligand entry, ligand
      binding and protein-protein interactions. Hence, the knowledge of protein
      structure and, importantly, the dynamic behaviour of the structure are critical
      for understanding how the protein performs its function. The predictions of the
      structure and the dynamic behaviour can be performed by combinations of structure
      modelling and molecular dynamics simulations. The simulations also need to be
      sensitive to the constraints of the environment in which the protein resides.
      Standard computational methods now exist in this field to support the
      experimental effort of solving protein structures. This review presents a
      comprehensive overview of the basis of the calculations and the well-established
      computational methods used to generate and understand protein structure and
      function and the study of their dynamic behaviour with the reference to lung
      related targets.

PMID- 22155024
TI  - Clinical trial implementation and recruitment: lessons learned from the early
      closure of a randomized clinical trial.
AB  - BACKGROUND: The NHLBI-sponsored Sickle Cell Disease Clinical Research Network
      (SCDCRN) conducted a multi-center, acute intervention randomized clinical trial
      of two methods of Patient Controlled Analgesia for acute pain. This trial was
      terminated early due to low enrollment. We analyzed the perceived barriers and
      recruitment difficulties as reported by the coordinators and principal
      investigators. METHODS: Participating sites completed a missed eligibility log of
      subjects admitted in pain crisis throughout the study and a survey at the end of
      the trial. The survey covered site-specific factors, policies, and procedures in
      study implementation, recruitment strategies, and eligibility factors. The New
      England Research Institutes (NERI) collected de-identified surveys from 31
      respondents at 29 of 31 participating sites. RESULTS: From December 2009 to June
      2010, 1116 patient encounters for SCD and pain occurred at participating
      institutions: 38 subjects were enrolled (14 pediatric and 24 adults) and 34
      completed the trial, below the projected 278 subjects. Fourteen sites enrolled
      subjects and seventeen did not. Recruitment barriers included insufficient staff,
      subject ineligibility or in too much pain to consent, competing protocols, and
      concerns regarding pain control. Recruitment methods were referrals from urgent
      care, SCD clinics and in house databases. No use of media or outside physicians
      was reported. CONCLUSION: We identified multiple barriers to patient accrual
      including short duration of enrollment period, protocol design, complex dosing
      schedule, requirement for staff availability during week-end and after hours,
      multiple departments' involvement, protocol acceptance, eligibility criteria,
      competing protocols, and limited staff. Each of these areas should be targeted
      for intervention in order to plan and conduct successful future clinical trials.

PMID- 22155027
TI  - Test-retest variability underlying fMRI measurements.
AB  - INTRODUCTION: A high test-retest reliability is of pivotal importance for many
      disciplines in fMRI research. To assess the current limits of fMRI reliability,
      we estimated the variability in true underlying Blood Oxygen Level Dependent
      (BOLD) activation, with which we mean the variability that would be found in the
      theoretical case when we could obtain an unlimited number of scans in each
      measurement. METHODS: In this test-retest study, subjects were scanned twice with
      one week apart, while performing a visual and a motor inhibition task. We
      addressed the nature of the variability in the underlying BOLD signal, by
      separating for each brain area and each subject the between-session differences
      in the spatial pattern of BOLD activation, and the global (whole brain) changes
      in the amplitude of the spatial pattern of BOLD activation. RESULTS: We found
      evidence for changes in the true underlying spatial pattern of BOLD activation
      for both tasks across the two sessions. The sizes of these changes in pattern
      activation were approximately 16% of the total activation within the pattern,
      irrespective of brain area and task. After spatial smoothing, this variability
      was greatly reduced, which suggests it takes place at a small spatial scale. The
      mean between-session differences in the amplitude of activation across the whole
      brain were 13.8% for the visual task and 23.4% for the motor inhibition task.
      CONCLUSIONS: Between-session changes in the true underlying spatial pattern of
      BOLD activation are always present, but occur at a scale that is consistent with
      partial voluming effects or spatial distortions. We found no evidence that the
      reliability of the spatial pattern of activation differs systematically between
      brain areas. Consequently, between-session changes in the amplitude of activation
      are probably due to global effects. The observed variability in amplitude across
      sessions warrants caution when interpreting fMRI estimates of height of brain
      activation. A Matlab implementation of the used algorithm is available for
      download at www.ni-utrecht.nl/downloads/ura.

PMID- 22155028
TI  - Genetic influences on thinning of the cerebral cortex during development.
AB  - During development from childhood to adulthood the human brain undergoes
      considerable thinning of the cerebral cortex. Whether developmental cortical
      thinning is influenced by genes and if independent genetic factors influence
      different parts of the cortex is not known. Magnetic resonance brain imaging was
      done in twins at age 9 (N = 190) and again at age 12 (N = 125; 113 repeated
      measures) to assess genetic influences on changes in cortical thinning. We find
      considerable thinning of the cortex between over this three year interval (on
      average 0.05 mm; 1.5%), particularly in the frontal poles, and orbitofrontal,
      paracentral, and occipital cortices. Cortical thinning was highly heritable at
      age 9 and age 12, and the degree of genetic influence differed for the various
      areas of the brain. One genetic factor affected left inferior frontal (Broca's
      area), and left parietal (Wernicke's area) thinning; a second factor influenced
      left anterior paracentral (sensory-motor) thinning. Two factors influenced
      cortical thinning in the frontal poles: one of decreasing influence over time,
      and another independent genetic factor emerging at age 12 in left and right
      frontal poles. Thus, thinning of the cerebral cortex is heritable in children
      between the ages 9 and 12. Furthermore, different genetic factors are responsible
      for variation in cortical thickness at ages 9 and 12, with independent genetic
      factors acting on cortical thickness across time and between various brain areas
      during childhood brain development.

PMID- 22155029
TI  - Model selection and gobbledygook: response to Lohmann et al.
AB  - Lohmann et al. (this issue) make three unremarkable observations about model
      selection and use them to critique dynamic causal modelling-a Bayesian model
      selection procedure based on causal models of dynamical systems (Marreiros et
      al., 2010). In this response, we unpack their misconceptions and try to answer
      their questions.

PMID- 22155030
TI  - Anxiolytic-like effect of pregabalin on unconditioned fear in the rat: an
      autoradiographic brain perfusion mapping and functional connectivity study.
AB  - Clinical and preclinical evidence suggests anxiolytic-like efficacy of pregabalin
      (PGB, Lyrica). However, its mechanism of action remains under investigation. The
      current study applied [(14)C]-iodoantipyrine cerebral blood flow (CBF) mapping to
      examine the effect of PGB on neural substrates underlying unconditioned fear in a
      rat model of footshock-induced fear. Regional CBF (rCBF) was analyzed by
      statistical parametric mapping. Functional connectivity and graph theoretical
      analysis were used to investigate how footshock and PGB affect brain activation
      at the network level. Pregabalin significantly attenuated footshock-induced
      ultrasonic vocalization, but showed no significant effect on freezing behavior.
      Footshock compared to no-shock controls elicited significant increases in rCBF in
      limbic/paralimbic regions implicated in the processing of unconditioned fear and
      ultrasonic vocalization, including the amygdala, hypothalamus, lateral septum,
      dorsal periaqueductal gray, the anterior insular (aINS) and medial prefrontal
      cortex (mPFC). The activation pattern was similar in vehicle- and PGB-treated
      subjects, with PGB significantly attenuating activation in the amygdala,
      hypothalamus, and aINS. The vehicle/no-shock group showed strong, positive intra
      structural correlations within the cortex, hypothalamus, amygdala, thalamus, and
      brainstem. The cortex was negatively correlated with the hypothalamus and
      brainstem. Footshock reduced the total number of significant correlations, but
      induced greater intra-cortical connectivity of the aINS and mPFC, and new
      positive correlations between the hypothalamus and amygdala. In no-shock
      controls, PGB significantly reduced the positive intra-structural correlations
      within the cortex and amygdala, as well as the negative cortico-subcortical
      correlations. Following footshocks, PGB disrupted both the network recruitment of
      aINS and mPFC, and the positive hypothalamic-amygdaloid correlations. Our
      findings suggest that PGB may exert anxiolytic effect by attenuating cortico
      cortical and cortico-subcortical communication and inhibiting network recruitment
      of the aINS, mPFC, amygdala, and hypothalamus following a fear-inducing stimulus.
      Functional brain mapping in rodents may provide new endpoints for preclinical
      evaluation of anxiolytic drug candidates with potentially improved translational
      power compared to behavioral measurements alone.

PMID- 22155031
TI  - Somatosensory activation of two fingers can be discriminated with ultrahigh
      density diffuse optical tomography.
AB  - Topographic non-invasive near infrared spectroscopy (NIRS) has become a well
      established tool for functional brain imaging. Applying up to 100 optodes over
      the head of a subject, allows achieving a spatial resolution in the centimeter
      range. This resolution is poor compared to other functional imaging tools.
      However, recently it was shown that diffuse optical tomography (DOT) as an
      extension of NIRS based on high-density (HD) probe arrays and supplemented by an
      advanced image reconstruction procedure allows describing activation patterns
      with a spatial resolution in the millimeter range. Building on these findings, we
      hypothesize that HD-DOT may render very focal activations accessible which would
      be missed by the traditionally used sparse arrays. We examined activation
      patterns in the primary somatosensory cortex, since its somatotopic organization
      is very fine-grained. We performed a vibrotactile stimulation study of the first
      and fifth finger in eight human subjects, using a 900-channel continuous-wave DOT
      imaging system for achieving a higher resolution than conventional topographic
      NIRS. To compare the results to a well-established high-resolution imaging
      technique, the same paradigm was investigated in the same subjects by means of
      functional magnetic resonance imaging (fMRI). In this work, we tested the
      advantage of ultrahigh-density probe arrays and show that highly focal
      activations would be missed by classical next-nearest neighbor NIRS approach, but
      also by DOT, when using a sparse probe array. Distinct activation patterns for
      both fingers correlated well with the expected neuroanatomy in five of eight
      subjects. Additionally we show that activation for different fingers is projected
      to different tissue depths in the DOT image. Comparison to the fMRI data yielded
      similar activation foci in seven out of ten finger representations in these five
      subjects when comparing the lateral localization of DOT and fMRI results.

PMID- 22155032
TI  - Characterization of [11C]RO5013853, a novel PET tracer for the glycine
      transporter type 1 (GlyT1) in humans.
AB  - We characterize a novel radioligand for the glycine transporter type 1 (GlyT1),
      [(11)C]RO5013853, in humans. Ten healthy male volunteers, 23-60 years of age,
      were enrolled in this PET study; seven subjects participated in the evaluation of
      test-retest reliability and three subjects in whole body dosimetry. Subjects were
      administered intravenous bolus injections of approximately 1100 MBq (30 mCi)
      [(11)C]RO5013853 with a high specific activity of about 481 GBq (13 Ci)/MUmol.
      Standard compartmental model analysis with arterial plasma input function, and an
      alternative noninvasive analysis method which was evaluated and validated by
      occupancy studies in both baboons and humans, were performed. Mean parameter
      estimates of the volumes of distribution (VT) obtained by a 2-tissue 5-parameter
      model were higher in the cerebellum, pons, and thalamus (1.99 to 2.59 mL/mL), and
      lower in the putamen, caudate, and cortical areas (0.86 to 1.13 mL/mL), with
      estimates showing less than 10% difference between test and retest scans. Tracer
      retention was effectively blocked by the specific glycine reuptake inhibitor
      (GRI), bitopertin (RG1678). [(11)C]RO5013853 was safe and well tolerated. Human
      dosimetry studies showed that the effective dose was approximately 0.0033
      mSv/MBq, with the liver receiving the highest absorbed dose. In conclusion,
      quantitative dynamic PET of the human brain after intravenous injection of
      [(11)C]RO5013853 attains reliable measurements of GlyT1 binding in accordance
      with the expected transporter distribution in the human brain. [(11)C]RO5013853
      is a radioligand suitable for further clinical PET studies. Full characterization
      of a novel radiotracer for GlyT1 in humans is provided. The tracer has
      subsequently been used to assess receptor occupancy in healthy volunteers and to
      estimate occupancy at doses associated with best efficacy in a clinical trial
      with schizophrenic patients with predominantly negative symptoms.

PMID- 22155033
TI  - Unconscious translation during incidental foreign language processing.
AB  - It is generally accepted that word processing in bilinguals is language
      nonselective. However, this has mostly been shown in contexts involving
      deliberate processing focusing on a particular aspect of linguistic information
      (e.g., lexicality, semantic category, relatedness). It is therefore unknown to
      what extent non-target language access is only apparent in overt language
      processing contexts. Here, we examined the effect of involuntary word processing
      in bilingual individuals performing a nonverbal judgment task on shapes. Chinese
      English bilinguals had to differentiate between circles and squares by pressing
      buttons while ignoring intervening English words. In the critical trials, the to
      be-ignored words concealed a sound repetition with the words "circle" or "square"
      when translated into Chinese. In these trials, we found increased N200 event
      related potential amplitudes, reflecting inhibition in this condition as compared
      to the control condition, in which the intervening words were totally unrelated
      to the shapes. Since no lateralised readiness potential effect was found in this
      comparison, access to Chinese translations must have been quickly inhibited,
      consistent with the fact that we observed no behavioural effects of the hidden
      manipulation. These results suggest fast and unconscious language nonselective
      access even when no language task is being performed.

PMID- 22155034
TI  - Bone morphogenetic protein-3b (BMP-3b) inhibits osteoblast differentiation via
      Smad2/3 pathway by counteracting Smad1/5/8 signaling.
AB  - Despite the involvement of BMP-3b (also called GDF-10) in osteogenesis,
      embryogenesis and adipogenesis, the functional receptors and intracellular
      signaling of BMP-3b have yet to be elucidated. In the present study, we
      investigated the cellular mechanism of BMP-3b in osteoblast differentiation using
      mouse myoblastic C2C12 cells. BMP-3b stimulated activin/TGF-beta-responsive
      promoter activities. The stimulatory actions of BMP-3b on activin/TGF-beta
      responsive activities were suppressed by co-treatment with BMP-2. BMP-responsive
      promoter activities stimulated by BMP-2 were significantly inhibited by treatment
      with BMP-3b. BMP-3b suppressed the expression of osteoblastic markers including
      Runx2, osteocalcin and type-1 collagen induced by BMP-2, -4, -6 and -7. BMP-2
      induced Smad1/5/8 phosphorylation and mRNA levels of the BMP target gene Id-1
      were suppressed by co-treatment with BMP-3b, although BMP-3b failed to activate
      Smad1/5/8 signaling. Of interest, the BMP-3b suppression of BMP-2-induced Id-1
      expression was not observed in cells overexpressing Smad4 molecules. On the other
      hand, BMP-3b directly activated Smad2/3 phosphorylation and activin/TGF-beta
      target gene PAI-1 mRNA expression, while BMP-2 suppressed BMP-3b-induced Smad2/3
      signal activation. BMP-2 inhibition of BMP-3b-induced PAI-1 expression was also
      reversed by overexpression of Smad4. Analysis using inhibitors for BMP-Smad1/5/8
      pathways revealed that these BMP-3b effects were mediated via receptors other
      than ALK-2, -3 and -6. Furthermore, results of inhibitory studies using
      extracellular domains for BMP receptor constructs showed that the activity of BMP
      3b was functionally facilitated by a combination of ALK-4 and ActRIIA.
      Collectively, BMP-3b plays an inhibitory role in the process of osteoblast
      differentiation, in which BMP-3b and BMP-2 are mutually antagonistic possibly by
      competing with the availability of Smad4.

PMID- 22155035
TI  - Effect of rearing water temperature on protandrous sex inversion in cultured
      Asian Seabass (Lates calcarifer).
AB  - Asian Seabass, Lates calcarifer (Bloch, 1790), is a protandrous species cultured
      for Aquaculture. The cultured Asian Seabass in Australia exhibits precocious sex
      inversion before 2years of age. This phenomenon highly affects on maintaining a
      proper broodstock in a hatchery. The effect of temperature on sex inversion
      inducement in Asian Seabass was thus investigated at five different temperature
      regimes experienced in Australia. Asian Seabass (14months) grown in fresh water
      under natural temperature in a commercial farm in Queensland were transported to
      the research facility at James Cook University, Australia and held in fresh water
      at 28 degrees C until acclimatized to the experimental conditions. Fish were
      acclimated to the experimental conditions (30ppt salinity) over the first and
      final week (22 degrees C, 25 degrees C, 28 degrees C, 31 degrees C and 34 degrees
      C) of one month acclimatizing period. Fish were fed daily with a commercial
      pellet (50% protein, 18MJkg(-1)) to satiety. Blood, brain and gonad collected
      before transfer to the experimental temperature regime in the final week of
      acclimatization and at the end of the experiment were analysed. Plasma sex
      steroids level and aromatase activity of brain and gonad were also measured.
      There was an increase in plasma estradiol levels with increasing temperature from
      25 degrees C while no significant difference was observed among all treatment
      temperatures except at 25 degrees C. However, fish held at 22 degrees C showed
      higher estradiol level than at 25 degrees C and 28 degrees C. Significantly
      higher (p<0.05) plasma testosterone levels were detected in fish held at 31
      degrees C and 34 degrees C while a reducing trend was observed towards lower
      temperature regimes. Fish held at 22 degrees C had significantly lower plasma
      testosterone than all others as well those sampled at the beginning. The plasma
      11-ketoTestosterone was at non-detectable levels in all experimental temperatures
      as shown at the beginning. The average aromatase activity in brain was highest at
      28 degrees C among all temperatures, but no significant differences (p>0.05)
      observed. The Average aromatase activity in gonad was highest at 31 degrees C
      followed by at 34 degrees C and 28 degrees C. No or very low level of gonad
      aromatase activity recorded in fish sacrificed prior to treatment. The aromatase
      activity was greater in brain than in gonad suggesting that the aromatase
      produced in the brain yet to transfer to the gonad or brain is the first place to
      response for culture environmental temperature. It is concluded that plasma sex
      steroids levels and aromatase activity in Asian Seabass have positive response to
      increasing temperature in culture facilities.

PMID- 22155036
TI  - Comparative analysis of the UDP-glycosyltransferase multigene family in insects.
AB  - UDP-glycosyltransferases (UGT) catalyze the conjugation of a range of diverse
      small lipophilic compounds with sugars to produce glycosides, playing an
      important role in the detoxification of xenobiotics and in the regulation of
      endobiotics in insects. Recent progress in genome sequencing has enabled an
      assessment of the extent of the UGT multigene family in insects. Here we report
      over 310 putative UGT genes identified from genomic databases of eight different
      insect species together with a transcript database from the lepidopteran
      Helicoverpa armigera. Phylogenetic analysis of the insect UGTs showed Order
      specific gene diversification and inter-species conservation of this multigene
      family. Only one family (UGT50) is found in all insect species surveyed (except
      the pea aphid) and may be homologous to mammalian UGT8. Three families (UGT31,
      UGT32, and UGT305) related to Lepidopteran UGTs are unique to baculoviruses. A
      lepidopteran sub-tree constructed with 40 H. armigera UGTs and 44 Bombyx mori
      UGTs revealed that lineage-specific expansions of some families in both species
      appear to be driven by diversification in the N-terminal substrate binding
      domain, increasing the range of compounds that could be detoxified or regulated
      by glycosylation. By comparison of the deduced protein sequences, several
      important domains were predicted, including the N-terminal signal peptide, UGT
      signature motif, and C-terminal transmembrane domain. Furthermore, several
      conserved residues putatively involved in sugar donor binding and catalytic
      mechanism were also identified by comparison with human UGTs. Many UGTs were
      expressed in fat body, midgut, and Malpighian tubules, consistent with functions
      in detoxification, and some were expressed in antennae, suggesting a role in
      pheromone deactivation. Transcript variants derived from alternative splicing,
      exon skipping, or intron retention produced additional UGT diversity. These
      findings from this comparative study of two lepidopteran UGTs as well as other
      insects reveal a diversity comparable to this gene family in vertebrates, plants
      and fungi and show the magnitude of the task ahead, to determine biochemical
      function and physiological relevance of each UGT enzyme.

PMID- 22155037
TI  - Effect of proanthocyanidin incorporation into dental adhesive resin on resin
      dentine bond strength.
AB  - OBJECTIVES: This study evaluated the effect of proanthocyanidin (PA)
      incorporation into experimental dental adhesives on resin-dentine bond strength.
      METHODS: Four experimental hydrophilic adhesives containing different PA
      concentrations were prepared by combining 50wt% resin comonomer mixtures with
      50wt% ethanol. Proanthocyanidin was added to the ethanol-solvated resin to yield
      three adhesives with PA concentrations of 1.0, 2.0 and 3.0wt%, respectively. A PA
      free adhesive served as the control. Flat dentine surfaces from 40 extracted
      third molars were etched with 32% phosphoric acid. The specimens were randomly
      assigned to one of the four adhesive groups. Two layers of one of the four
      experimental adhesives were applied to the etched dentine and light-cured for
      20s. Composite build-ups were performed using Filtek Z250 (3M ESPE). After
      storage in distilled water at 37 degrees C for 24h, twenty-four bonded teeth were
      sectioned into 0.9 mm*0.9 mm beams and stressed to failure under tension for bond
      strength testing. Bond strength data were evaluated by one-way ANOVA and Tukey's
      test (alpha=0.05). Interfacial nanoleakage was examined in the remaining teeth
      using a field-emission scanning electron microscope and analysed using the Chi
      square test (alpha=0.05). RESULTS: No significant difference in bond strength was
      found amongst PA-free, 1% and 2% PA adhesives. However, incorporation of 3% PA
      into the adhesive significantly lowered bond strength as demonstrated by a
      greater number of adhesive failures and more extensive nanoleakage along the
      bonded interface. CONCLUSION: Incorporation of 2% proanthocyanidin into dental
      adhesives has no adverse effect on dentine bond strength. CLINICAL SIGNIFICANCE:
      The addition of proanthocyanidin to an experimental adhesive has no adverse
      effect on the immediate resin-dentine bond strength when the concentration of
      proanthocyanidin in the adhesive is less than or equal to 2%.

PMID- 22155038
TI  - Dexmedetomidine directly inhibits vascular ATP-sensitive potassium channels.
AB  - AIMS: Dexmedetomidine is reported to have an effect on peripheral
      vasoconstriction; however, the exact mechanisms underlying this process are
      unclear. In this study, we hypothesized that dexmedetomidine-induced inhibition
      of vascular ATP-sensitive K(+) (K(ATP)) channels may be associated with this
      vasoconstriction. To test this hypothesis, we investigated the effects of
      dexmedetomidine on vascular K(ATP)-channel activity at the single-channel level.
      MAIN METHODS: We used cell-attached and inside-out patch-clamp configurations to
      examine the effects of dexmedetomidine on the activities of native rat vascular
      K(ATP) channels, recombinant K(ATP) channels with different combinations of
      various inwardly rectifying potassium channels (Kir6.0 family: Kir6.1, 6.2) and
      sulfonylurea receptor subunits (SUR1, 2A, 2B), and SUR-deficient channels derived
      from a truncated isoform of Kir6.2 subunit, namely, Kir6.2DeltaC36 channels. KEY
      FINDINGS: Dexmedetomidine was observed to inhibit the native rat vascular K(ATP)
      channels in both cell-attached and inside-out configurations. This drug also
      inhibited the activity of all types of recombinant SUR/Kir6.0 K(ATP) channels as
      well as Kir6.2DeltaC36 channels with equivalent potency. SIGNIFICANCE: These
      results indicate that dexmedetomidine directly inhibits K(ATP) channels through
      the Kir6.0 subunit.

PMID- 22155039
TI  - Estimation of functional connectivity in fMRI data using stability selection
      based sparse partial correlation with elastic net penalty.
AB  - Characterizing interactions between multiple brain regions is important for
      understanding brain function. Functional connectivity measures based on partial
      correlation provide an estimate of the linear conditional dependence between
      brain regions after removing the linear influence of other regions. Estimation of
      partial correlations is, however, difficult when the number of regions is large,
      as is now increasingly the case with a growing number of large-scale brain
      connectivity studies. To address this problem, we develop novel methods for
      estimating sparse partial correlations between multiple regions in fMRI data
      using elastic net penalty (SPC-EN), which combines L1- and L2-norm regularization
      We show that L1-norm regularization in SPC-EN provides sparse interpretable
      solutions while L2-norm regularization improves the sensitivity of the method
      when the number of possible connections between regions is larger than the number
      of time points, and when pair-wise correlations between brain regions are high.
      An issue with regularization-based methods is choosing the regularization
      parameters which in turn determine the selection of connections between brain
      regions. To address this problem, we deploy novel stability selection methods to
      infer significant connections between brain regions. We also compare the
      performance of SPC-EN with existing methods which use only L1-norm regularization
      (SPC-L1) on simulated and experimental datasets. Detailed simulations show that
      the performance of SPC-EN, measured in terms of sensitivity and accuracy is
      superior to SPC-L1, especially at higher rates of feature prevalence. Application
      of our methods to resting-state fMRI data obtained from 22 healthy adults shows
      that SPC-EN reveals a modular architecture characterized by strong inter
      hemispheric links, distinct ventral and dorsal stream pathways, and a major hub
      in the posterior medial cortex - features that were missed by conventional
      methods. Taken together, our findings suggest that SPC-EN provides a powerful
      tool for characterizing connectivity involving a large number of correlated
      regions that span the entire brain.

PMID- 22155040
TI  - Single trial discrimination of individual finger movements on one hand: a
      combined MEG and EEG study.
AB  - It is crucial to understand what brain signals can be decoded from single trials
      with different recording techniques for the development of Brain-Machine
      Interfaces. A specific challenge for non-invasive recording methods are
      activations confined to small spatial areas on the cortex such as the finger
      representation of one hand. Here we study the information content of single trial
      brain activity in non-invasive MEG and EEG recordings elicited by finger
      movements of one hand. We investigate the feasibility of decoding which of four
      fingers of one hand performed a slight button press. With MEG we demonstrate
      reliable discrimination of single button presses performed with the thumb, the
      index, the middle or the little finger (average over all subjects and fingers
      57%, best subject 70%, empirical guessing level: 25.1%). EEG decoding performance
      was less robust (average over all subjects and fingers 43%, best subject 54%,
      empirical guessing level 25.1%). Spatiotemporal patterns of amplitude variations
      in the time series provided best information for discriminating finger movements.
      Non-phase-locked changes of mu and beta oscillations were less predictive.
      Movement related high gamma oscillations were observed in average induced
      oscillation amplitudes in the MEG but did not provide sufficient information
      about the finger's identity in single trials. Importantly, pre-movement neuronal
      activity provided information about the preparation of the movement of a specific
      finger. Our study demonstrates the potential of non-invasive MEG to provide
      informative features for individual finger control in a Brain-Machine Interface
      neuroprosthesis.

PMID- 22155041
TI  - Functional organization of the left inferior precentral sulcus: dissociating the
      inferior frontal eye field and the inferior frontal junction.
AB  - Two eye fields have been described in the human lateral frontal cortex: the
      frontal eye field (FEF) and the inferior frontal eye field (iFEF). The FEF has
      been extensively studied and has been found to lie at the ventral part of the
      superior precentral sulcus. Much less research, however, has focused on the iFEF.
      Recently, it was suggested that the iFEF is located at the dorsal part of the
      inferior precentral sulcus. A similar location was proposed for the inferior
      frontal junction area (IFJ), an area thought to be involved in cognitive control
      processes. The present study used fMRI to clarify the topographical and
      functional relationship of the iFEF and the IFJ in the left hemispheres of
      individual participants. The results show that both the iFEF and the IFJ are
      indeed located at the dorsal part of the inferior precentral sulcus.
      Nevertheless, the activations were spatially dissociable in every individual
      examined. The IFJ was located more towards the depth of the inferior precentral
      sulcus, close to the junction with the inferior frontal sulcus, whereas the iFEF
      assumed a more lateral, posterior and superior position. Furthermore, the results
      provided evidence for a functional double dissociation: the iFEF was activated
      only in a comparison of saccades vs. button presses, but not in a comparison of
      incongruent vs. congruent Stroop conditions, while the opposite pattern was found
      at the IFJ. These results provide evidence for a spatial and functional
      dissociation of two directly adjacent areas in the left posterior frontal lobe.

PMID- 22155042
TI  - Serotonin-1A receptors in major depression quantified using PET: controversies,
      confounds, and recommendations.
AB  - The serotonin-1A (5-HT(1A)) receptor is of particular interest in human positron
      emission tomography (PET) studies of major depressive disorder (MDD). Of the
      eight studies investigating this issue in the brains of patients with MDD, four
      reported decreased 5-HT(1A) receptor density, two reported no change, and two
      reported increased 5-HT(1A) receptor density. While clinical heterogeneity may
      have contributed to these differing results, methodological factors by themselves
      could also explain the discrepancies. This review highlights several of these
      factors, including the use of the cerebellum as a reference region and the
      imprecision of measuring the concentration of parent radioligand in arterial
      plasma, the method otherwise considered to be the 'gold standard'. Other
      potential confounds also exist that could restrict or unexpectedly affect the
      interpretation of results. For example, the radioligand may be a substrate for an
      efflux transporter - like P-gp - at the blood-brain barrier; furthermore, the
      binding of the radioligand to the receptor in various stages of cellular
      trafficking is unknown. Efflux transport and cellular trafficking may also be
      differentially expressed in patients compared to healthy subjects. We believe
      that, taken together, the existing disparate findings do not reliably answer the
      question of whether 5-HT(1A) receptors are altered in MDD or in subgroups of
      patients with MDD. In addition, useful meta-analysis is precluded because only
      one of the imaging centers acquired all the data necessary to address these
      methodological concerns. We recommend that in the future, individual centers
      acquire more thorough data capable of addressing methodological concerns, and
      that multiple centers collaborate to meaningfully pool their data for meta
      analysis.

PMID- 22155043
TI  - A spatiotemporal dynamic distributed solution to the MEG inverse problem.
AB  - MEG/EEG are non-invasive imaging techniques that record brain activity with high
      temporal resolution. However, estimation of brain source currents from surface
      recordings requires solving an ill-conditioned inverse problem. Converging lines
      of evidence in neuroscience, from neuronal network models to resting-state
      imaging and neurophysiology, suggest that cortical activation is a distributed
      spatiotemporal dynamic process, supported by both local and long-distance
      neuroanatomic connections. Because spatiotemporal dynamics of this kind are
      central to brain physiology, inverse solutions could be improved by incorporating
      models of these dynamics. In this article, we present a model for cortical
      activity based on nearest-neighbor autoregression that incorporates local
      spatiotemporal interactions between distributed sources in a manner consistent
      with neurophysiology and neuroanatomy. We develop a dynamic maximum a posteriori
      expectation-maximization (dMAP-EM) source localization algorithm for estimation
      of cortical sources and model parameters based on the Kalman Filter, the Fixed
      Interval Smoother, and the EM algorithms. We apply the dMAP-EM algorithm to
      simulated experiments as well as to human experimental data. Furthermore, we
      derive expressions to relate our dynamic estimation formulas to those of standard
      static models, and show how dynamic methods optimally assimilate past and future
      data. Our results establish the feasibility of spatiotemporal dynamic estimation
      in large-scale distributed source spaces with several thousand source locations
      and hundreds of sensors, with resulting inverse solutions that provide
      substantial performance improvements over static methods.

PMID- 22155044
TI  - Pattern analysis of EEG responses to speech and voice: influence of feature
      grouping.
AB  - Pattern recognition algorithms are becoming increasingly used in functional
      neuroimaging. These algorithms exploit information contained in temporal,
      spatial, or spatio-temporal patterns of independent variables (features) to
      detect subtle but reliable differences between brain responses to external
      stimuli or internal brain states. When applied to the analysis of
      electroencephalography (EEG) or magnetoencephalography (MEG) data, a choice needs
      to be made on how the input features to the algorithm are obtained from the
      signal amplitudes measured at the various channels. In this article, we consider
      six types of pattern analyses deriving from the combination of three types of
      feature selection in the temporal domain (predefined windows, shifting window,
      whole trial) with two approaches to handle the channel dimension (channel wise,
      multi-channel). We combined these different types of analyses with a Gaussian
      Naive Bayes classifier and analyzed a multi-subject EEG data set from a study
      aimed at understanding the task dependence of the cortical mechanisms for
      encoding speaker's identity and speech content (vowels) from short speech
      utterances (Bonte, Valente, & Formisano, 2009). Outcomes of the analyses showed
      that different grouping of available features helps highlighting complementary
      (i.e. temporal, topographic) aspects of information content in the data. A
      shifting window/multi-channel approach proved especially valuable in tracing both
      the early build up of neural information reflecting speaker or vowel identity and
      the late and task-dependent maintenance of relevant information reflecting the
      performance of a working memory task. Because it exploits the high temporal
      resolution of EEG (and MEG), such a shifting window approach with sequential
      multi-channel classifications seems the most appropriate choice for tracing the
      temporal profile of neural information processing.

PMID- 22155045
TI  - Individualized localization and cortical surface-based registration of
      intracranial electrodes.
AB  - In addition to its widespread clinical use, the intracranial electroencephalogram
      (iEEG) is increasingly being employed as a tool to map the neural correlates of
      normal cognitive function as well as for developing neuroprosthetics. Despite
      recent advances, and unlike other established brain-mapping modalities (e.g.
      functional MRI, magneto- and electroencephalography), registering the iEEG with
      respect to neuroanatomy in individuals-and coregistering functional results
      across subjects-remains a significant challenge. Here we describe a method which
      coregisters high-resolution preoperative MRI with postoperative computerized
      tomography (CT) for the purpose of individualized functional mapping of both
      normal and pathological (e.g., interictal discharges and seizures) brain
      activity. Our method accurately (within 3mm, on average) localizes electrodes
      with respect to an individual's neuroanatomy. Furthermore, we outline a
      principled procedure for either volumetric or surface-based group analyses. We
      demonstrate our method in five patients with medically-intractable epilepsy
      undergoing invasive monitoring of the seizure focus prior to its surgical
      removal. The straight-forward application of this procedure to all types of
      intracranial electrodes, robustness to deformations in both skull and brain, and
      the ability to compare electrode locations across groups of patients makes this
      procedure an important tool for basic scientists as well as clinicians.

PMID- 22155046
TI  - Automated delineation of white matter fiber tracts with a multiple region-of
      interest approach.
AB  - White matter fiber bundles of the brain can be delineated by tractography
      utilizing multiple regions-of-interest (MROI) defined by anatomical landmarks.
      These MROI can be used to specify regions in which to seed, select, or reject
      tractography fibers. Manual identification of anatomical MROI enables the
      delineation of white matter fiber bundles, but requires considerable training to
      develop expertise, considerable time to carry out and suffers from unwanted inter
      and intra-rater variability. In a study of 20 healthy volunteers, we compared
      three methodologies for automated delineation of the white matter fiber bundles.
      Using these methodologies, fiber bundle MROI for each volunteer were
      automatically generated. We assessed three strategies for inferring the automatic
      MROI utilizing nonrigid alignment of reference images and projection of template
      MROI. We assessed the bundle delineation error associated with alignment
      utilizing T1-weighted MRI, fractional anisotropy images, and full tensor images.
      We confirmed the smallest delineation error was achieved using the full tensor
      images. We then assessed three projection strategies for automatic determination
      of MROI in each volunteer. Quantitative comparisons were made using the root-mean
      squared error observed between streamline density images constructed from fiber
      bundles identified automatically and by manually drawn MROI in the same subjects.
      We demonstrate that a multiple template consensus label fusion algorithm
      generated fiber bundles most consistent with the manual reference standard.

PMID- 22155047
TI  - Phase synchronization of foot dynamics in quiet standing.
AB  - This study was set-up to investigate the effect of mechanical constraints arising
      from different postural stances on the AP and ML pattern of the time evolutionary
      properties of phase synchronization of the foot dynamics, together with their
      relation to the dynamics of COP(NET). The results showed that postural stance
      differentially influenced the phase synchronization (number and duration of the
      epochs) between the individual feet COPs and of each foot to the COP(NET). The
      side-by-side stance had longer phase synchronization duration in the anterior
      posterior (AP) direction and shorter duration in the medial-lateral (ML)
      direction than the staggered and tandem postures. In the staggered and tandem
      postures, the relative phase between the rear foot COP and the COP(NET) had
      longer phase synchronization than the relative phase between the COPs of the two
      feet and that between the front foot COP and the COP(NET). The time evolutionary
      properties of the feet coupling dynamics revealed patterns of "stable" but
      "flexible" control of the postural system as a function of the asymmetrical foot
      loading in the stance.

PMID- 22155048
TI  - Co-administration of apocynin with lipoic acid enhances neuroprotection in a rat
      model of ischemia/reperfusion.
AB  - Apocynin is a well-known NADPH-oxidase inhibitor currently being investigated for
      its potential therapeutic use in patients with cardiovascular disease, such as
      occlusive stroke. However, the use of apocynin as a potential neuroprotective
      agent has come under criticism due to a narrow experimental therapeutic dose
      range and possible pro-oxidant effects at high doses. Lipoic acid is a powerful
      antioxidant due to its ability to scavenge free radicals at very low doses and
      has been demonstrated to enhance the therapeutic value of several other classes
      of drugs. Therefore, the present study was designed to determine if co
      administration of previously determined non-neuroprotective doses of lipoic acid
      and apocynin in combination could enhance their neuroprotective ability thus
      extending the therapeutic dose range. We tested the hypothesis in a rat model of
      stroke and reperfusion injury. The middle cerebral artery (MCA) in male Sprague
      Dawley rats was occluded for 30 min followed by 5.5h of reperfusion. Pre
      treatment with several doses of apocynin (0.05, 0.1 and 1.0 mg/kg) in combination
      with a single dose of lipoic acid (0.005 mg/kg) resulted in a dose-dependent
      reduction in infarct volume up to ~50%. These results demonstrate that a non
      effective dose of lipoic acid can enhance the neuroprotective ability of apocynin
      at doses which were previously demonstrated to be non-neuroprotective. Co
      administration of apocynin with lipoic acid may overcome the criticisms of the
      use of apocynin as a neuroprotectant and provide an effective therapy in the
      prevention of cell death following stroke.

PMID- 22155049
TI  - C19, a C-terminal peptide of chemokine-like factor 1, protects the brain against
      focal brain ischemia in rats.
AB  - There has been accumulating evidence that chemokines play an important role in
      cerebral ischemia. Chemokines-like factor 1 (CKLF1), as a novel C-C chemokine, is
      upregulated in cerebral ischemia. In this study we examined the protective effect
      of C19, a C-terminal peptide of chemokine-like factor 1, in an animal model of
      cerebral ischemia. Adult rats were anesthetized with chloral hydrate. C19 was
      given intracerebroventricularly immediately after 60 min middle cerebral artery
      occlusion. Animals were examined for their neurological function, infarct size
      and water content at 24h after reperfusion. The result showed that C19 (0.1, 1,
      10 or 50 MUg) significantly improved neurological function, decreased infarct
      size and water content in a dose-dependent manner. In contrast, application of
      C19 (50 MUg) showed no effect in normal rats. Taken together, our data suggest
      that C19 is protective against ischemic brain injury, and may be an ideal peptide
      drug for the treatment of cerebral ischemia.

PMID- 22155050
TI  - Dissociable contributions of motor-execution and action-observation to
      intermanual transfer.
AB  - We examined the suggestion that some of the processes subserving learning through
      action-observation and motor-execution are different because sensory motor
      reafference is not available while the limb is at rest in the former condition.
      We confirmed the action-observation and motor-execution groups learned equally
      the absolute time and relative time constraints associated with a movement
      sequence timing task. However, data from mirror (same motor commands as those in
      practice) and non-mirror (same visual spatial coordinates as those in practice)
      intermanual transfer tests showed a clear dissociation in performance following
      these forms of practice. While positive transfer was exhibited by both groups in
      the non-mirror condition, there was a significant decrement in relative time
      performance in the mirror condition only after action-observation. These findings
      confirm that some of the processes underpinning these forms of motor learning are
      not somatotopic. Indeed, while motor and visual representations are developed
      during motor-execution, the absence of sensorimotor reafference during action
      observation enables relative time to be represented in visual spatial coordinates
      only. These behavioural effects for intermanual transfer are discussed with
      reference to activity in supplementary motor area.

PMID- 22155051
TI  - The molecular basis of retinal ganglion cell death in glaucoma.
AB  - Glaucoma is a group of diseases characterized by progressive optic nerve
      degeneration that results in visual field loss and irreversible blindness. A
      crucial element in the pathophysiology of all forms of glaucoma is the death of
      retinal ganglion cells (RGCs), a population of CNS neurons with their soma in the
      inner retina and axons in the optic nerve. Strategies that delay or halt RGC loss
      have been recognized as potentially beneficial to preserve vision in glaucoma;
      however, the success of these approaches depends on an in-depth understanding of
      the mechanisms that lead to RGC dysfunction and death. In recent years, there has
      been an exponential increase in valuable information regarding the molecular
      basis of RGC death stemming from animal models of acute and chronic optic nerve
      injury as well as experimental glaucoma. The emerging landscape is complex and
      points at a variety of molecular signals - acting alone or in cooperation - to
      promote RGC death. These include: axonal transport failure, neurotrophic factor
      deprivation, toxic pro-neurotrophins, activation of intrinsic and extrinsic
      apoptotic signals, mitochondrial dysfunction, excitotoxic damage, oxidative
      stress, misbehaving reactive glia and loss of synaptic connectivity.
      Collectively, this body of work has considerably updated and expanded our view of
      how RGCs might die in glaucoma and has revealed novel, potential targets for
      neuroprotection.

PMID- 22155052
TI  - Activity measurement of protein kinase and protein phosphatase by microchip
      phosphate-affinity electrophoresis.
AB  - We previously proposed microchip-based phosphate-affinity electrophoresis (MUPAE)
      and demonstrated its application to activity measurement of a tyrosine kinase, c
      Src. In this study, we extended the MUPAE application to a serine/threonine
      kinase, protein kinase A (PKA), and to a tyrosine phosphatase, leukocyte antigen
      related protein tyrosine phosphatase (LAR PTPase). For standard peptide samples,
      we obtained linear calibration plots, and the limits of detection were 1.2% (PKA)
      and 1.5% (LAR PTPase) product peptides in the total peptides. The MUPAE was also
      proven to be effective for unpurified enzyme reaction products.

PMID- 22155053
TI  - Horizontal carryover of proteins on one-dimensional polyacrylamide gels may
      jeopardize gel-enhanced liquid chromatography mass spectrometry proteomic
      interpretations.
AB  - Mass spectrometric identification of gel-separated proteins is a cornerstone of
      many proteomic efforts. Often the protein compositions of two neighboring lanes
      (typically representing the experiment and control) are compared assuming that
      proteins are separated only in a vertical dimension and do not spread
      horizontally. However, we noticed that horizontal protein spreading commonly
      occurs on one-dimensional polyacrylamide gels and might lead to a misleading
      judgment regarding the presence or absence of particular proteins even in the
      distantly spaced lanes. Therefore, we suggest that experimental and control
      samples should always be loaded on separate gels.

PMID- 22155054
TI  - Rare target enrichment for ultrasensitive PCR detection using cot-rehybridization
      and duplex-specific nuclease.
AB  - Nucleic acid detection by polymerase chain reaction (PCR) is invaluable for the
      detection of dilute and rare sequences, including pathogens and infrequent
      species in complex clinical and environmental backgrounds. The presence of excess
      complex background nucleic acid can reduce sensitivity and specificity. This is
      because mispriming can cause failure of the amplification reaction. Here we
      describe a new approach to ultrasensitive PCR detection, using enrichment of rare
      target nucleic acid from abundant background by combining the classic technique
      of cot-rehybridization to convert the abundant background to double-stranded
      form, with the use of a newly described, highly processive duplex-specific crab
      nuclease. We show that trace sequences in a vast excess of background DNA can be
      undetectable by PCR, independent of the amount of the mixture added to the PCR,
      and that these sequences can be made detectable by background suppression using
      this method.

PMID- 22155055
TI  - Detection of Edwardsiella tarda by fluorometric or biosensor methods using a
      peptide ligand.
AB  - In this study, we identified a peptide ligand for Edwardsiella tarda from a phage
      peptide library and tested two approaches for sensitive detection of the bacteria
      with the peptide labeled with fluorescein or biotin. At first, the fluorescent
      peptide was proved to be advantageous in the fluorescence polarization (FP) assay
      because sensitivity of the assay is maximized when a fluorophore is linked to a
      small molecule. The FP assay using the fluorescent peptide enabled detection of
      E. tarda in a range from 5.2*10(3) to 2.1*10(5) cells. Second, we devised a new
      assay method using a quartz crystal microbalance (QCM) biosensor connected to a
      filter module. When a mixture of E. tarda and the biotinylated peptide was
      injected into the filter module, the E. tarda-peptide complex was separated from
      the unbound peptide by a filter and detected with a streptavidin-coated QCM
      sensor chip. On injection of samples containing the biotinylated peptide and E.
      tarda, concentration-dependent frequency change was observed in a range from
      8*10(2) to 8*10(6) cells. The two approaches are expected to facilitate
      development of assay methods using other bacteria-binding peptides.

PMID- 22155056
TI  - Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated
      inhibition of transforming growth factor-beta/Smad signaling.
AB  - Sulforaphane (SFN) is a dietary isothiocyanate that exerts chemopreventive
      effects via NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase
      II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1
      (NQO1). This work was undertaken to evaluate the effects of SFN on hepatic
      fibrosis and profibrotic transforming growth factor (TGF)-beta/Smad signaling,
      which are closely associated with oxidative stress. SFN suppressed TGF-beta
      enhanced expression of alpha-smooth muscle actin (alpha-SMA), a marker of hepatic
      stellate cell (HSC) activation, and profibrogenic genes such as type I collagen,
      fibronectin, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and
      plasminogen activator inhibitor (PAI)-1 in hTERT, an immortalized human HSC line.
      SFN inhibited TGF-beta-stimulated activity of a PAI-1 promoter construct and
      (CAGA)(9) MLP-Luc, an artificial Smad3/4-specific reporter, in addition to
      reducing phosphorylation and nuclear translocation of Smad3. Nrf2 overexpression
      was sufficient to inhibit the TGF-beta/Smad signaling and PAI-1 expression.
      Conversely, knockdown of Nrf2, but not inhibition of HO-1 or NQO1 activity,
      significantly abolished the inhibitory effect of SFN on (CAGA)(9) MLP-Luc
      activity. However, inhibition of NQO1 activity reversed repression of TGF-beta
      stimulated expression of type I collagen by SFN, suggesting the involvement of
      antioxidant activity of SFN in the suppression of Smad-independent fibrogenic
      gene expression. Finally, SFN treatment attenuated the development and
      progression of early stage hepatic fibrosis induced by bile duct ligation in
      mice, accompanied by reduced expression of type I collagen and alpha-SMA.
      Collectively, these results show that SFN elicits an antifibrotic effect on
      hepatic fibrosis through Nrf2-mediated inhibition of the TGF-beta/Smad signaling
      and subsequent suppression of HSC activation and fibrogenic gene expression.

PMID- 22155057
TI  - Fragmentation of a linoleate-derived gamma-hydroperoxy-alpha,beta-unsaturated
      epoxide to gamma-hydroxy- and gamma-oxo-alkenals involves a unique pseudo
      symmetrical diepoxycarbinyl radical.
AB  - Many of the pathological effects of lipid peroxidation are mediated by aldehydes
      generated through fragmentation of lipid peroxides. Among these aldehydes, the
      gamma-hydroxy- and gamma-oxo-alpha,beta-alkenals, e.g., 4-hydroxy-2-nonenal (HNE)
      and 4-oxo-2-nonenal (ONE), are especially prone to modifying proteins and DNA
      through covalent adduction. In addition the "mirror image" gamma-hydroxy- and
      gamma-oxo-alpha,beta-alkenal phospholipids can serve as high-affinity ligands for
      biological receptors triggering pathology. Therefore, the mechanisms by which
      these aldehydes are generated in vivo are under intense scrutiny. We now report
      observations supporting the intermediacy of a unique pseudo-symmetrical
      diepoxycarbinyl radical that accounts for the coproduction of HNE, ONE, and their
      mirror image analogues 9-hydroxy-12-oxo-10(E)-dodecenoic acid and 9-keto-12-oxo
      10-dodecenoic acid upon fragmentation of 13-hydroperoxy-cis-9,10-epoxyoctadeca-11
      enoic acid.

PMID- 22155058
TI  - Biochemical and biological characterization of Escherichia coli STb His12 to Asn
      variant.
AB  - We identified a variant of Escherichia coli STb toxin by PCR amplification of
      clinical isolates obtained from diseased pigs. The variant differed by only one
      amino acid at position 12 from His to Asn. This change was observed in 23 of the
      100 randomly selected enterotoxigenic E. coli (ETEC) isolates tested. There was a
      positive correlation between the presence of the STa enterotoxin and the STb
      variant. As the variant represented a high percentage of the ETEC strains tested,
      we were interested in determining if the single amino acid change results in
      altered biological characteristics of the toxin. Circular dichroism analysis
      revealed that the secondary structure of the variant was similar to wildtype and
      that their thermal stabilities were similar. Surface plasmon resonance showed
      that the variant and the wildtype toxins possessed similar binding affinities for
      sulfatide but the variant exhibited a reduced binding capacity. A flow cytometry
      based internalization assay showed that the variant toxin is more internalized
      into epithelial intestinal cells than the wildtype strain. However, this
      difference was minor. Overall, our results indicate that while wildtype STb and
      the variant share similar structural properties, modest differences exist in
      their internalization.

PMID- 22155059
TI  - Comment on "Can muscle coordination be precisely studied by surface
      electromyography?".

PMID- 22155060
TI  - Evaluation of electromyography normalisation methods for the back squat.
AB  - The aim of the study was to evaluate maximal isometric (dynamometer based {MVC
      NORM} and isometric squat {MIS-NORM}) and sub-maximal EMG normalisation methods
      (60%-NORM, 70%-NORM, 80%-NORM) for dynamic back squat exercise (DSQ-EX). The
      absolute reliability (limits of agreement {LOA}, coefficient of variation {CV%}),
      relative reliability (intra-class correlation coefficient {ICC}) and sensitivity
      of each method was assessed. Ten resistance-trained males attended four sessions.
      Session one assessed maximum back squat strength (three repetition maximum
      {3RM}). In the remaining three sessions Vastus lateralis (VL) and Bicep femoris
      (BF) EMG were measured whilst participants completed normalisation tasks and DSQ
      EX sets at 65%, 75%, 85% and 95% of 3RM. MIS-NORM produced lower intra
      participant CV% compared to MVC-NORM. 80%-NORM produced lower intra-participant
      CV% than other sub-maximal methods for VL and BF during eccentric and concentric
      phases. 80%-NORM also produced narrower 95% LOA results than all other
      normalisation methods. The MIS-NORM method displayed higher ICC values for both
      muscles during eccentric and concentric phases. The 60%-NORM and 70%-NORM methods
      were the most sensitive for VL and BF during eccentric and concentric phases.
      Only normalisation methods for the concentric action of the VL enhanced
      sensitivity compared to unnormalised EMG. Overall, dynamic normalisation methods
      demonstrated better absolute reliability and sensitivity for reporting VL and BF
      EMG within the current study compared to maximal isometric methods.

PMID- 22155061
TI  - Phlebotominae fauna in a recent deforested area with American tegumentary
      leishmaniasis transmission (Puerto Iguazu, Misiones, Argentina): seasonal
      distribution in domestic and peridomestic environments.
AB  - Phlebotominae sand flies have been involved as vectors of Leishmania. In
      Argentina, Nyssomyia neivai and Nyssomyia whitmani are involved as the main
      vectors of American Tegumentary Leishmaniasis (ATL). In the northeastern border
      of the country, an outbreak of ATL during 2004-2005 was associated with
      deforestation and subsequent settlement of farmers close to the edge of the
      forest. The aim of this work was to study the community composition of sand flies
      along time in farms located near primary and secondary forest in two
      environments: houses and pigsties. The association of abundance with temperature
      and precipitation was also evaluated for the most prevalent species. A total of
      23,659 Phlebotominae belonging to the genera Nyssomyia, Migonemyia, Pintomyia,
      Evandromyia, Micropygomyia, Sciopemyia, Dampfomyia, Psathyromyia and Brumptomyia
      were captured. Ny. whitmani, which was the most abundant species, and Migonemyia
      migonei, which was the second most abundant species, were present throughout the
      year. Both species were positively associated with temperature, mostly up to 31
      47 days, and with precipitation at 31 days before the sampling day. The abundance
      was higher in pigsties than in houses, but the time pattern was positively
      associated between both environments. These results confirm that Ny. whitmani is
      the dominant species in the study area and its presence throughout the year
      indicates a potential long period of ATL transmission. The presence of Mg.
      migonei as the second species in abundance is relevant, because it has been
      described as a secondary vector of the parasites of ATL and a putative vector of
      the agent of American Visceral Leishmaniasis. We discuss the role of the pigsty
      as the environment that attract more sandflies, taking into account the number of
      sand flies captured there, the distance from the home, and the association of
      sand fly abundance with each of the two environments.

PMID- 22155062
TI  - Metalloregulation of Gram-positive pathogen physiology.
AB  - Owing to the unique redox potential of transition metals, many of these elements
      serve important roles as cofactors in numerous enzymes. However, the reactive
      nature of metal becomes an intracellular threat when these ions are present in
      excess. Therefore, all organisms require mechanisms for sensing small
      fluctuations in metal levels to maintain a controlled balance of uptake, efflux,
      and sequestration. The ability to sense metal ion concentration is especially
      important for the survival of pathogenic bacteria because host organisms can both
      restrict access to essential metals from invading pathogens and utilize the
      innate toxicity of certain metals for bacterial killing. Host-induced metal ion
      fluctuations must be rapidly sensed by pathogenic bacteria so that they can
      activate metal transport systems, alter their physiology to accommodate
      differences in metal concentrations, and regulate the expression of virulence
      factors.

PMID- 22155063
TI  - Comparison of weekly versus every 3 weeks paclitaxel in the treatment of advanced
      solid tumors: a meta-analysis.
AB  - BACKGROUND: Paclitaxel is commonly given as a 3-h infusion every 3 weeks for a
      variety of malignancies. Several randomized clinical trials comparing weekly
      paclitaxel with Q3-week (Q3W) have produced mixed results in terms of efficacy
      and toxicity creating controversy about the ideal dose and schedule. METHODS: A
      literature search using PubMed, Cochrane Library, and Proceedings of the American
      Society of Clinical oncology from 1995 to 2011 was performed. We included all
      published and registered RTCs for advanced solid tumors which compared weekly
      paclitaxel with Q3W. Primary dependent variables--grade 3, 4 neutropenia rates
      and grade 3 sensory neuropathy rates--were analyzed for all cancer types.
      Secondary dependent variables--hazard ratios for survival and response rates-
      were analyzed for each cancer type. Moderators of cancer types, ethnicity, and
      paclitaxel dose ratio were analyzed for primary dependent variables. RESULTS: Ten
      trials were included. The summary effects of the meta-analysis revealed less
      grade 3, 4 neutropenia (odds ratio: 0.49, p=0.0023) and a trend towards less
      grade 3 sensory neuropathy (odds ratio: 0.54, p=0.092) with weekly paclitaxel
      compared with Q3W. Moderator analysis by meta-regression revealed that paclitaxel
      dose ratios have a significantly positive correlation with rates of G3/4
      neutropenia and sensory neuropathy. In the five NSCLC (non small cell lung
      cancer) trials, the summary effect revealed a better response rate with weekly
      paclitaxel (odds ratio: 1.24, p=0.042). CONCLUSION: Weekly paclitaxel has a
      favorable toxicity profile compared to the current standard of Q3W paclitaxel.

PMID- 22155064
TI  - The effects of low arched feet on lower limb gait kinematics in children.
AB  - BACKGROUND: The effects of foot posture on the dynamic function of the lower limb
      during gait remains relatively unknown. OBJECTIVES: The purpose of this study was
      to investigate lower limb kinematics between the normal and low arched foot
      during the gait cycle, particularly in the transverse plane. METHOD: Twenty-four
      children, twelve with normal and twelve with low arched feet, aged 11-12 years
      underwent a lower limb three dimensional gait analysis. Temporo-spatial
      parameters and patterns and ranges of motion of kinematic data were examined for
      the pelvis, hip, knee and ankle throughout the gait cycle. RESULTS: Overall,
      there were very few differences found in the kinematics of the lower limbs
      between the normal and low arched group. Increased external hip rotation (6-7
      degrees ) in the low arched group was the only bilateral significant difference
      (p<0.05) between the two foot groups. No significant differences existed in any
      temporo-spatial parameters between the two groups. CONCLUSIONS: The increased
      external hip rotation and greater external foot progression angle in the low
      arched foot highlights the need to examine gait comprehensively to establish
      cause or effect of these differences observed and hence determine appropriate
      treatment.

PMID- 22155065
TI  - Open porous microscaffolds for cellular and tissue engineering by lipid
      templating.
AB  - Porous microspheres fabricated from biodegradable polymers have great potential
      as microscaffolds in tissue engineering applications, especially for novel
      strategies such as microtissue fabrication in vitro and microtissue assembly in
      vivo. Fabrication techniques for microparticulate scaffolds with surface and bulk
      pore sizes relevant for effective cell intrusion, however, are scarce. This study
      presents two techniques for the fabrication of open porous microscaffolds from
      poly(lactide-co-glycolide) in which lipid templating is used for pore formation
      and combined with either dispersion spraying or a double emulsion technique to
      determine the size and shape of the particulate structures generated. Both
      techniques yield microscaffolds with an average size of between 500 and 800 MUm,
      high bulk porosities and open surface pores larger than 50 MUm in diameter.
      Microscaffold morphology was investigated microscopically, particle size
      distribution was determined and porosity was quantified by intrusion
      measurements. Particle size and morphology was controlled by the processing
      parameters and the content and type of lipid porogen. Efficient extraction of the
      lipid template was shown by thermal analysis. Microscaffold cytocompatibility and
      in vitro cell culture performance was evaluated with L929 fibroblasts and rat
      adipose-derived stromal cells (ADSC), respectively. Extracts of different
      formulations were cytocompatible. Rat ADSC proliferated on the microscaffolds and
      were differentiated along the adipogenic lineage.

PMID- 22155066
TI  - A peptide-modified chitosan-collagen hydrogel for cardiac cell culture and
      delivery.
AB  - Myocardial infarction (MI) results in the death of cardiomyocytes (CM) followed
      by scar formation and pathological remodeling of the heart. We propose that
      chitosan conjugated with the angiopoietin-1 derived peptide, QHREDGS, and mixed
      with collagen I forms a thermoresponsive hydrogel better suited for the survival
      and maturation of transplanted cardiomyocytes in vitro compared to collagen and
      chitosan-collagen hydrogels alone. Conjugation of QHREDGS peptide to chitosan
      does not interfere with the gelation, structure or mechanical properties of the
      hydrogel blends. The storage modulus of 2.5 mg ml(-1) 1:1 mass:mass (m:m)
      chitosan-collagen was measured to be 54.9 +/- 9.1 Pa, and the loss modulus 6.1+/
      0.9 Pa. The dose-response of the QHREDGS peptide was assessed and it was found
      that CMs encapsulated in High-peptide gel (651 +/- 8 nmol peptide ml-gel(-1))
      showed improved morphology, viability and metabolic activity in comparison to the
      Low-peptide (100 +/- 30 nmol peptide ml-gel(-1)) and Control (No Peptide) groups.
      Construct (CMs in hydrogel) functional properties were not significantly
      different between the groups; however, the success rate of obtaining a beating
      construct was improved in the hydrogel with the High amount of QHREDGS peptide
      immobilized compared to the Low and Control groups. Subcutaneous injection of
      hydrogel (Control, Low and High) with CMs in the back of Lewis rats illustrated
      its ability to localize at the site of injection and retain cells, with CM
      contractile apparati identified after seven days. The hydrogel was also able to
      successfully localize at the site of injection in a mouse MI model.

PMID- 22155067
TI  - Restriction enzyme-free construction of random gene mutagenesis libraries in
      Escherichia coli.
AB  - Directed evolution relies on both random and site-directed mutagenesis of
      individual genes and regulatory elements to create variants with altered activity
      profiles for engineering applications. Central to these experiments is the
      construction of large libraries of related variants. However, a number of
      technical hurdles continue to limit routine construction of random mutagenesis
      libraries in Escherichia coli, in particular, inefficiencies during digestion and
      ligation steps. Here, we report a restriction enzyme-free approach to library
      generation using megaprimers termed MegAnneal. Target DNA is first exponentially
      amplified using error-prone polymerase chain reaction (PCR) and then linearly
      amplified with a single 3' primer to generate long, randomly mutated, single
      stranded megaprimers. These are annealed to single-stranded dUTP-containing
      template plasmid and extended with T7 polymerase to create a complementary
      strand, and the resulting termini are ligated with T4 DNA ligase. Using this
      approach, we are able to reliably generate libraries of approximately 107 colony
      forming units (cfu)/MUg DNA/transformation in a single day. We have created
      MegAnneal libraries based on three different single-chain antibodies and
      identified variants with enhanced expression and ligand-binding affinity. The key
      advantages of this approach include facile amplification, restriction enzyme-free
      library generation, and a significantly reduced risk of mutations outside the
      targeted region and wild-type contamination as compared with current methods.

PMID- 22155068
TI  - Digestion of restriction enzyme for the detection of single-base mismatch in DNA.
AB  - DNA hybridization and enzymatic digestion for the detection of mutation was
      investigated on the gold nanoparticles-calf thymus DNA (AuNPs-ctDNA) modified
      glassy carbon electrode (GCE). The thiol modified probe oligonucleotides (SH
      ssDNA) were assembled on the surface of AuNPs-ctDNA modified GCE. The
      electrochemical response of the electrode was measured by differential pulse
      voltammetry and cyclic voltammetry. Methylene blue (MB) was used as the
      electroactive indicator. AuNPs were then dispersed effectively on the GCE surface
      in the presence of ct-DNA. When hybridization occurred, a decrease in the signal
      of MB current was observed. The modified electrode was used for the detection of
      mutations during the enzymatic digestion reaction in DNA. During this reaction,
      an increase in the signal of MB current was observed. So, the modified SH-ssDNA
      had a higher electrochemical response on the AuNPs-ctDNA/GCE because of the
      strong affinity of MB for guanine residues in it. The electrochemical detection
      of restriction enzyme digestion can provide a simple and practical method for
      observing single-base mismatches that can help in distinguishing mismatch
      sequences of DNA from the complementary ones.

PMID- 22155069
TI  - Synthesis of NaYF(4):Yb/Er/Gd up-conversion luminescent nanoparticles and
      luminescence resonance energy transfer-based protein detection.
AB  - High-quality NaYF4:Yb/Er/Gd up-conversion nanoparticles (UCNPs) were first
      synthesized by a solvothermal method using rare earth stearate, sodium fluoride,
      ethanol, water, and oleic acid as precursors. Doped Gd3+ ions can promote the
      transition of NaYF4 from cubic to hexagonal phase, shorten the reaction time, and
      reduce the reaction temperature without reducing the luminescence intensity of
      NaYF4:Yb/Er UCNPs. X-ray diffraction, infrared spectroscopy, transmission
      electron microscopy, and luminescence spectroscopy were applied to characterize
      the UCNPs. The nanoparticles exhibited small size and excellent green up
      conversion photoluminescence, making them suitable for biological applications.
      After the surfaces of NaYF4:Yb/Er/Gd UCNPs were modified with amino groups
      through the Stober method, they could be brought close enough to the analytically
      important protein called R-phycoerythrin (R-PE) bearing multiple carboxyl groups
      so that energy transfer could occur. A luminescence resonance energy transfer
      (LRET) system was developed using NaYF4:Yb/Er/Gd UCNPs as an energy donor and R
      PE as an energy acceptor. As a result, a detection limit of R-PE of 0.5 MUg/ml
      was achieved by the LRET system with a relative standard deviation of 2.0%.
      Although this approach was first used successfully to detect R-PE, it can also be
      extended to the detection of other biological molecules.

PMID- 22155070
TI  - Severe gastro-intestinal angiodysplasia in context of Heyde's syndrome durably
      cured after aortic valve replacement.

PMID- 22155071
TI  - [Indolent deep ulcer: Buruli ulcer].

PMID- 22155072
TI  - Electronic health technology for the assessment of physical activity and eating
      habits in children and adolescents with overweight and obesity IDA.
AB  - OBJECTIVE: It was the goal of the trial to study the impact of electronic
      healthcare technology into treatment. METHODS: One hundred and twenty-four
      children/adolescents (females 56%, age 13.5+/-2.8 years, height 1.64+/-0.13 m,
      weight 85.4+/-23.0 kg, body-mass index (BMI) 31.3+/-5.2 kg/m(2), BMI-standard
      deviation score (SDS) 2.50+/-0.5) were included. To assess physical activity and
      eating habits, a mobile motion sensor integrated into a mobile phone with digital
      camera was used. RESULTS: The children/adolescents had a significant weight
      reduction of 7.1+/-3.0 kg. BMI/BMI-SDS decreased (p<0.01). Intensity (14.1+/-6.4
      activity units) and duration of physical activity (290.4+/-92.6 min/day) were
      assessed with sensors. Time walking: median 45.5 (range, 2.5-206.5), running 8.0
      (range, 0-39.5), cycling 27.7 (range, 0-72.5), car driving 23.7 (range, 0-83.0)
      min/day. Comparing self-reported physical activity (walking 292.9 (range, 9.6
      496.1), running 84.8 (range, 8.4-130.2) min/day) with assessment with sensors
      there were significant differences (p<0.01). Duration of physical activity
      documented by children/adolescents was higher than the assessment with motion
      sensors (walking 292.9 vs 45.5 min, p<0.01, running 84.8 vs 8.0 min, p<0.01).
      Sensor derived energy intake was higher than recommended (469.14+/-88.75 kcal vs
      489.03+/-108.25 kcal, p=0.09). Performing multivariate analysis the following
      parameters showed associations with weight reduction (R-square=0.75): body weight
      (beta=-0.95, p<0.01), C-reactive protein (CRP, beta=0.15, p=0.07), physical
      activity, time spent in activities measured with sensors (beta=-0.18, p=0.04),
      stress management (beta=0.16, p=0.06), body fat mass at onset of the trial
      (beta=0.45, p<0.01) and body shape (beta=-0.25, p=0.01). CONCLUSION: The
      innovative mobile movement detection system is highly accepted by children and
      adolescents. The system is able to augment existing weight reduction and
      stabilization strategies.

PMID- 22155073
TI  - Monotonous consumption of fibre-enriched bread at breakfast increases satiety and
      influences subsequent food intake.
AB  - This study aimed to observe the influence of the monotonous consumption of two
      types of fibre-enriched bread at breakfast on hedonic liking for the bread,
      subsequent hunger and energy intake. Two groups of unrestrained normal weight
      participants were given either white sandwich bread (WS) or multigrain sandwich
      bread (MG) at breakfast (the sensory properties of the WS were more similar to
      the usual bread eaten by the participants than those of the MG). In each group,
      two 15-day cross-over conditions were set up. During the experimental condition
      the usual breakfast of each participant was replaced by an isocaloric portion of
      plain bread (WS or MG). During the control condition, participants consumed only
      10 g of the corresponding bread and completed their breakfast with other foods
      they wanted. The results showed that bread appreciation did not change over
      exposure even in the experimental condition. Hunger was lower in the experimental
      condition than in the control condition. The consumption of WS decreased energy
      intake while the consumption of MG did not in the experimental condition compared
      to the corresponding control one. In conclusion, a monotonous breakfast composed
      solely of a fibre-enriched bread may decrease subsequent hunger and, when similar
      to a familiar bread, food intake.

PMID- 22155074
TI  - Patient acceptable symptom state and OMERACT-OARSI set of responder criteria in
      joint replacement. Identification of cut-off values.
AB  - OBJECTIVE: To identify new cut-off values beyond which patients can be considered
      as satisfied or as responders through patient acceptable symptom state (PASS) and
      OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society
      International) set of responder criteria in total joint replacement. METHODS:
      Secondary analysis of a 1-year prospective multicenter study of 861 patients, 510
      with total knee replacement (TKR) and 351 with total hip prosthesis (THR). Pain
      and function data were collected by the reverse scoring option of the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC). PASS values were
      identified with the 25th centile estimation using an anchoring question about
      satisfaction with actual symptoms. OMERACT-OARSI set of responder criteria was
      based on a combination of absolute and relative change of pain, function and
      global patient's assessment. Receiver operating characteristic (ROC) analysis was
      used as a complementary approach. RESULTS: The values for PASS were about 80 and
      69 for pain and function in THR, while these values were 80 and 68 when using
      OMERACT-OARSI criteria. Regarding TKR, PASS values were about 75 and 67 in pain
      and function with both criteria. ROC values were slightly lower in all cases.
      PASS and OMERACT-OARSI values varied moderately across tertiles of baseline
      severity. CONCLUSION: With the provided data we can establish when a patient can
      be considered as satisfied/responder in joint replacement. The scores achieved at
      1 year were very similar according to both criteria.

PMID- 22155075
TI  - Inference of S-system models of genetic networks by solving one-dimensional
      function optimization problems.
AB  - Voit and Almeida have proposed the decoupling approach as a method for inferring
      the S-system models of genetic networks. The decoupling approach defines the
      inference of a genetic network as a problem requiring the solutions of sets of
      algebraic equations. The computation can be accomplished in a very short time, as
      the approach estimates S-system parameters without solving any of the
      differential equations. Yet the defined algebraic equations are non-linear, which
      sometimes prevents us from finding reasonable S-system parameters. In this study,
      we propose a new technique to overcome this drawback of the decoupling approach.
      This technique transforms the problem of solving each set of algebraic equations
      into a one-dimensional function optimization problem. The computation can still
      be accomplished in a relatively short time, as the problem is transformed by
      solving a linear programming problem. We confirm the effectiveness of the
      proposed approach through numerical experiments.

PMID- 22155076
TI  - Preoperative incisor inclination in patients with Class III dentofacial
      deformities treated with orthognathic surgery.
AB  - Our aim was to evaluate cephalometrically the preoperative inclination of the
      incisors in a group of 50 patients with Class III dentofacial deformities whose
      immediate preoperative lateral cephalometric radiographs were analysed after they
      had been treated by maxillary advancement. The radiographs were hand-traced by
      the same operator who made the cephalometric analysis. Mean values for each
      measurement were compared with the normal values using Student's t-test (p<0.05).
      Results showed significantly increased inclination of the upper incisors, with a
      mean U1-NA angle of 27.58 degrees  and a mean U1-PP angle of 116 degrees . The
      lower incisors were also inclined lingually, with a mean L1-NB angle of 22.53
      degrees  and a mean IMPA of 83.13 degrees . Thirty-five of the patients had
      labial inclination of the upper, and 28 lingual inclination of the lower,
      incisors. Mean inclinations of upper and lower incisors differed from the normal
      values, and the inclination of the lower incisors was more likely to be
      decompensated than that of the upper incisors.

PMID- 22155077
TI  - Iron mobilization from transferrin by therapeutic iron chelating agents.
AB  - BACKGROUND: The bacteriostatic activity of the transferrin family has been known
      since the early 1960's. The possession of high affinity iron(III)-binding sites
      and the existence of a specific membrane-bound receptor, have led to the present
      understanding of serum transferrin acting as the major iron transporter between
      cells in vertebrate systems. Iron chelators can interact with transferrin, either
      by directly donating iron or by removing iron from the protein; both interactions
      have relevance for haematology. SCOPE OF REVIEW: Urea polyacrylamide gels and
      HPLC methods have been developed for the resolution and quantification of the
      four major forms of transferrin, diferric-transferrin, C-mono Fe-transferrin, N
      mono Fe-transferrin and apo transferrin. MAJOR CONCLUSIONS: Negatively charged
      ligands with pFe values >20 remove iron from transferrin, preferably from the N
      lobe iron-binding site. Some siderophores are capable of removing iron from
      transferrin. 3-Hydroxypyridin-4-ones, lacking a negative charge are able to
      remove iron from transferrin with a strong preference for the C- lobe iron
      binding site. The donation of iron to apo transferrin by hydroxypyridinone
      iron(III) complexes has relevance to the treatment of clinical anaemias, because
      the hydroxypyridinones can also mobilize iron from the reticuloendothelial system
      and so facilitate the redistribution of iron from macrophages to reticulocytes.
      GENERAL SIGNIFICANCE: Hydroxypyridinones have excellent potential for
      facilitating the redistribution of iron and this has relevance to the treatment
      of many disease types, including neurodegeneration and clinical anaemias. This
      article is part of a Special Issue entitled Transferrins: Molecular mechanisms of
      iron transport and disorders.

PMID- 22155078
TI  - Analysis of the active-site mechanism of tyrosyl-DNA phosphodiesterase I: a
      member of the phospholipase D superfamily.
AB  - Tyrosyl-DNA phosphodiesterase I (Tdp1) is a member of the phospholipase D
      superfamily that hydrolyzes 3'-phospho-DNA adducts via two conserved catalytic
      histidines-one acting as the lead nucleophile and the second acting as a general
      acid/base. Substitution of the second histidine specifically to arginine
      contributes to the neurodegenerative disease spinocerebellar ataxia with axonal
      neuropathy (SCAN1). We investigated the catalytic role of this histidine in the
      yeast protein (His432) using a combination of X-ray crystallography,
      biochemistry, yeast genetics, and theoretical chemistry. The structures of wild
      type Tdp1 and His432Arg both show a phosphorylated form of the nucleophilic
      histidine that is not observed in the structure of His432Asn. The
      phosphohistidine is stabilized in the His432Arg structure by the guanidinium
      group that also restricts the access of nucleophilic water molecule to the Tdp1
      DNA intermediate. Biochemical analyses confirm that His432Arg forms an observable
      and unique Tdp1-DNA adduct during catalysis. Substitution of His432 by Lys does
      not affect catalytic activity or yeast phenotype, but substitutions with Asn,
      Gln, Leu, Ala, Ser, and Thr all result in severely compromised enzymes and DNA
      topoisomerase I-camptothecin dependent lethality. Surprisingly, His432Asn did not
      show a stable covalent Tdp1-DNA intermediate that suggests another catalytic
      defect. Theoretical calculations revealed that the defect resides in the
      nucleophilic histidine and that the pK(a) of this histidine is crucially
      dependent on the second histidine and on the incoming phosphate of the substrate.
      This represents a unique example of substrate-activated catalysis that applies to
      the entire phospholipase D superfamily.

PMID- 22155079
TI  - Effects of pathogenic proline mutations on myosin assembly.
AB  - Laing distal myopathy (MPD1) is a genetically dominant myopathy characterized by
      early and selective weakness of the distal muscles. Mutations in the MYH7 gene
      encoding for the beta-myosin heavy chain are the underlying genetic cause of
      MPD1. However, their pathogenic mechanisms are currently unknown. Here, we
      measure the biological effects of the R1500P and L1706P MPD1 mutations in
      different cellular systems. We show that, while the two mutations inhibit myosin
      self-assembly in non-muscle cells, they do not prevent incorporation of the
      mutant myosin into sarcomeres. Nevertheless, we find that the L1706P mutation
      affects proper antiparallel myosin association by accumulating in the bare zone
      of the sarcomere. Furthermore, bimolecular fluorescence complementation assay
      shows that the alpha-helix containing the R1500P mutation folds into homodimeric
      (mutant/mutant) and heterodimeric [mutant/wild type (WT)] myosin molecules that
      are competent for sarcomere incorporation. Both mutations also form aggregates
      consisting of cytoplasmic vacuoles surrounding paracrystalline arrays and
      amorphous rod-like inclusions that sequester WT myosin. Myosin aggregates were
      also detected in transgenic nematodes expressing the R1500P mutation. By showing
      that the two MPD1 mutations can have dominant effects on distinct components of
      the contractile apparatus, our data provide the first insights into the
      pathogenesis of the disease.

PMID- 22155081
TI  - The receptor-CheW binding interface in bacterial chemotaxis.
AB  - The basic structural unit of the signaling complex in bacterial chemotaxis
      consists of the chemotaxis kinase CheA, the coupling protein CheW, and
      chemoreceptors. These complexes play an important role in regulating the kinase
      activity of CheA and in turn controlling the rotational bias of the flagellar
      motor. Although individual three-dimensional structures of CheA, CheW, and
      chemoreceptors have been determined, the interaction between chemoreceptor and
      CheW is still unclear. We used nuclear magnetic resonance to characterize the
      interaction modes of chemoreceptor and CheW from Thermotoga maritima. We find
      that chemoreceptor binding surface is located near the highly conserved tip
      region of the N-terminal helix of the receptor, whereas the binding interface of
      CheW is placed between the beta-strand 8 of domain 1 and the beta-strands 1 and 3
      of domain 2. The receptor-CheW complex shares a similar binding interface to that
      found in the "trimer-of-dimers" oligomer interface seen in the crystal structure
      of cytoplasmic domains of chemoreceptors from Escherichia coli. Based on the
      association constants inferred from fast exchange chemical shifts associated with
      receptor-CheW titrations, we estimate that CheW binds about four times tighter to
      its first binding site of the receptor dimer than to its second binding site.
      This apparent anticooperativity in binding may reflect the close proximity of the
      two CheW binding surfaces near the receptor tip or further, complicating the
      events at this highly conserved region of the receptor. This work describes the
      first direct observation of the interaction between chemoreceptor and CheW.

PMID- 22155082
TI  - The educational hand and head: novel teaching tools in the design and execution
      of local flaps.

PMID- 22155080
TI  - Unwinding initiation by the viral RNA helicase NPH-II.
AB  - Viral RNA helicases of the NS3/NPH-II group unwind RNA duplexes by processive,
      directional translocation on one of the duplex strands. The translocation is
      preceded by a poorly understood unwinding initiation phase. For NPH-II from
      vaccinia virus, unwinding initiation is rate limiting for the overall unwinding
      reaction. To develop a mechanistic understanding of the unwinding initiation, we
      studied kinetic and thermodynamic aspects of this reaction phase for NPH-II in
      vitro, using biochemical and single molecule fluorescence approaches. Our data
      show that NPH-II functions as a monomer and that different stages of the ATP
      hydrolysis cycle dictate distinct binding preferences of NPH-II for duplex versus
      single-stranded RNA. We further find that the NPH-II-RNA complex does not adopt a
      single conformation but rather at least two distinct conformations in each of the
      analyzed stages of ATP hydrolysis. These conformations interconvert with rate
      constants that depend on the stage of the ATP hydrolysis cycle. Our data
      establish a basic mechanistic framework for unwinding initiation by NPH-II and
      suggest that the various stages of the ATP hydrolysis cycle do not induce single,
      stage-specific conformations in the NPH-II-RNA complex but primarily control
      transitions between multiple states.

PMID- 22155083
TI  - RE: Jalali et al. The UK plastic surgery trainee.

PMID- 22155084
TI  - Re: Dermoscopy - time for plastic surgeons to embrace a new diagnostic tool?

PMID- 22155085
TI  - Vacuum-assisted closure should not replace conventional therapy in the treatment
      of sternal wounds.

PMID- 22155086
TI  - The effect of adenotonsillectomy on serum insulin like growth factors and the
      adenoid/nasopharynx ratio in pediatric patients: a blind, prospective clinical
      study.
AB  - OBJECTIVES: Obstructive adenoid and tonsillar hyperplasia may present with
      retardation of growth. An adenoid-nasopharynx (A/N) ratio determined by means of
      lateral cephalometric radiographs has long been used as a diagnostic tool in the
      assessment of adenoid size. This study was designed to investigate the effect of
      adenotonsillectomy on insulin-like growth factor-I (IGF-I) and insulin-like
      growth factor binding protein-3 (IGFBP-3) levels and correlation between A/N
      ratio and IGF-I and IGFBP-3 levels. METHODS: Patients (n=48) that had been
      operated on our clinic with a diagnosis of adenotonsillar hypertrophy between
      July 2009 and January 2010 were included in the study. The routine ear-nose and
      throat examination was done in all patients. Blood samples were taken, and
      lateral cephalometric radiographs were obtained preoperatively and repeated at 6
      9 months (mean 7.2 +/- 1.0 mo) following tonsillectomy and adenoidectomy. The
      chemiluminescent enzyme-linked immunosorbent method was used to IGF-I and IGFBP-3
      levels. Each cephalometric radiograph was evaluated by a blinded radiologist. The
      A/N ratio was calculated using the Fujioka method. RESULTS: When the preoperative
      and postoperative results were compared, a statistically significant increase in
      serum IGF-I and IGFBP-3 and a decreased A/N ratio were found. However, although
      correlation between the Delta(preoperative-postoperative difference) IGFBP-3 and
      DeltaA/N ratio was 40%, it was not statistically significant. Additionally, no
      statistically significant correlation between the DeltaIGF-I and DeltaA/N ratio
      was found. CONCLUSIONS: The results of the present study indicate that
      adenotonsillectomy could result in the relief of nasopharyngeal obstruction and
      have a positive effect on growth in children by decreasing the A/N ratio and
      increasing IGF-I and IGFBP-3. There was no correlation between the DeltaA/N ratio
      and DeltaIGF-I and DeltaIGFBP-3 levels.

PMID- 22155087
TI  - Oligomerization paths of the nucleoprotein of influenza A virus.
AB  - The influenza viruses contain a segmented, negative strand RNA genome. Each RNA
      segment is covered by multiple copies of the nucleoprotein (NP) and is associated
      with the polymerase complex into ribonucleoprotein (RNP) particles. Despite its
      importance in the virus life cycle, the interactions between the NP and the
      genome are not well understood. Here, we studied the assembly process of NP-RNA
      oligomers and analyzed how the oligomeric/monomeric status of RNA-free NP affects
      RNA binding and oligomerization. Recombinant wild-type NP purified in low salt
      concentrations and a derived mutant engineered for oligomerization deficiency
      (R416A) were mainly monomeric in RNA-free solutions as shown by biochemical and
      electron microscopy techniques. NP monomer formed with RNA a fast 1/1 complex
      characterized by surface plasmon resonance. In a subsequent and slow process that
      depended on the RNA length, oligomerization of NP was mediated by RNA binding. In
      contrast, preparations of wild-type NP purified in high salt concentrations as
      well as mutant Y148A engineered for deficiency in nucleic acid binding were
      partly or totally oligomeric in RNA-free solutions. These trimer/tetramer NP
      oligomers bind directly as oligomers to RNA with a higher affinity than that of
      the monomers. Both oligomerization routes we characterized could be exploited by
      cellular or viral factors to modulate or control viral RNA encapsidation by NP.

PMID- 22155088
TI  - Identification of an active dimeric intermediate populated during the unfolding
      process of the cambialistic superoxide dismutase from Streptococcus mutans.
AB  - Superoxide dismutases are enzymes that protect biological systems against
      oxidative damage caused by superoxide radicals. In this paper, a detailed
      characterization is presented on the stability of SmSOD, the dimeric cambialistic
      superoxide dismutase from the dental pathogenic microorganism Streptococcus
      mutans, towards temperature and guanidine hydrochloride. Thermal and chemical
      denaturations were investigated by means of circular dichroism, fourth-derivative
      UV spectroscopy and fluorescence measurements. Data indicate that SmSOD is
      endowed with a significant thermostability and that both its thermal and
      guanidine hydrochloride-induced unfolding processes occur through a three-state
      model, characterized by a catalytically active dimeric intermediate species. To
      our knowledge, SmSOD is the smallest known dimeric protein that populates a well
      structured active dimeric rather than a monomeric intermediate during unfolding
      processes.

PMID- 22155089
TI  - Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles
      through an oxidative stress pathway.
AB  - Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to
      inhibit growth of mouse antral follicles, however, little is known about the
      mechanisms by which DEHP does so. Oxidative stress has been linked to follicle
      growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues.
      Thus, we hypothesized that DEHP causes oxidative stress and that this leads to
      inhibition of the growth of antral follicles. To test this hypothesis, antral
      follicles isolated from CD-1 mice (age 31-35days) were cultured with vehicle
      control (dimethylsulfoxide [DMSO]) or DEHP (1-100MUg/ml)+/-N-acetyl cysteine
      (NAC, an antioxidant at 0.25-1mM). During culture, follicles were measured daily.
      At the end of culture, follicles were collected and processed for in vitro
      reactive oxygen species (ROS) assays to measure the presence of free radicals or
      for measurement of the expression and activity of various key antioxidant
      enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and
      catalase (CAT). The results indicate that DEHP inhibits the growth of follicles
      compared to DMSO control and that NAC (0.25-1mM) blocks the ability of DEHP to
      inhibit follicle growth. Furthermore, DEHP (10MUg/ml) significantly increases ROS
      levels and reduces the expression and activity of SOD1 compared to DMSO controls,
      whereas NAC (0.5mM) rescues the effects of DEHP on ROS levels and SOD1. However,
      the expression and activity of GPX and CAT were not affected by DEHP treatment.
      Collectively, these data suggest that DEHP inhibits follicle growth by inducing
      production of ROS and by decreasing the expression and activity of SOD1.

PMID- 22155090
TI  - A pharmacologically-based array to identify targets of cyclosporine A-induced
      toxicity in cultured renal proximal tubule cells.
AB  - Mechanisms of cyclosporine A (CsA)-induced nephrotoxicity were generally thought
      to be hemodynamic in origin; however, there is now accumulating evidence of a
      direct tubular effect. Although genomic and proteomic experiments by our group
      and others provided overall information on genes and proteins up- or down
      regulated by CsA in proximal tubule cells (PTC), a comprehensive view of events
      occurring after CsA exposure remains to be described. For this purpose, we
      applied a pharmacologic approach based on the use of known activities of a large
      panel of potentially protective compounds and evaluated their efficacy in
      preventing CsA toxicity in cultured mouse PTC. Our results show that compounds
      that blocked protein synthesis and apoptosis, together with the CK2 inhibitor
      DMAT and the PI3K inhibitor apigenin, were the most efficient in preventing CsA
      toxicity. We also identified GSK3, MMPs and PKC pathways as potential targets to
      prevent CsA damage. Additionally, heparinase-I and MAPK inhibitors afforded
      partial but significant protection. Interestingly, antioxidants and calcium
      metabolism-related compounds were unable to ameliorate CsA-induced cytotoxicity.
      Subsequent experiments allowed us to clarify the hierarchical relationship of
      targeted pathways after CsA treatment, with ER stress identified as an early
      effector of CsA toxicity, which leads to ROS generation, phenotypical changes and
      cell death. In summary, this work presents a novel experimental approach to
      characterizing cellular responses to cytotoxics while pointing to new targets to
      prevent CsA-induced toxicity in proximal tubule cells.

PMID- 22155091
TI  - Differentially expressed gene profile in the 6-hydroxy-dopamine-induced cell
      culture model of Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by
      progressive loss of dopaminergic (DA) neurons of the substantia nigra pars
      compacta with unknown aetiology. 6-Hydroxydopamine (6-OHDA) treatment of neuronal
      cells is an established in vivo model for mimicking the effect of oxidative
      stress found in PD brains. We examined the effects of 6-OHDA treatment on human
      neuroblastoma cells (SH-SY5Y) and primary mesencephalic cultures. Using a reverse
      arbitrarily primed polymerase chain reaction (RAP-PCR) approach we generated
      reproducible genetic fingerprints of differential expression levels in cell
      cultures treated with 6-OHDA. Of the resulting sequences, 23 showed considerable
      homology to known human coding sequences. The results of the RAP-PCR were
      validated by reverse transcription PCR, real-time PCR and, for selected genes, by
      Western blot analysis and immunofluorescence. In four cases, [tomoregulin-1
      (TMEFF-1), collapsin response mediator protein 1 (CRMP-1), neurexin-1, and
      phosphoribosylaminoimidazole synthetase (GART)], a down-regulation of mRNA and
      protein levels was detected. Further studies will be necessary on the
      physiological role of the identified proteins and their impact on pathways
      leading to neurodegeneration in PD.

PMID- 22155092
TI  - In vitro seasonal variations of LH, FSH and prolactin secretion of the male rat
      are dependent on the maternal pineal gland.
AB  - The maternal pineal gland is involved in the seasonal rhythms entrainment. We
      evaluate the effect of maternal pinealectomy (PIN-X), also melatonin replacement
      (PIN-X+MEL) during pregnancy on "in vitro" gonadotropins and prolactin seasonal
      variations. Male offspring from control, PIN-X and PIN-X+MEL mother Wistar rats
      were studied at 31 and 60 days of age. In vitro LH release from controls was
      season-dependent during prepubertal and pubertal periods showing reduced values
      in winter. The mother pineal gland seems to be important in the entrainment of
      seasonal variations of in vitro pituitary LH release, since altered secretion
      showing very high values was observed in summer. Melatonin treatment to PIN-X
      mothers partially restored the LH response. The effect of pinealectomy upon LH
      secretion disappears at the pubertal phase. A different pattern was observed for
      FSH release, without seasonal variations at 31 or at 60 days of age in control
      offspring, but pinealectomy to mothers or melatonin treatment resulted in
      seasonal variations. Seasonal influence was also observed in the prolactin
      pituitary release of controls. PIN-X mother offspring showed delayed seasonal
      variations at 31 and 60 days of age. The effect of maternal melatonin treatment
      during pregnancy was observed up to 60 days of age.

PMID- 22155093
TI  - The neural processing of fearful faces without attention and consciousness: an
      event-related potential study.
AB  - To investigate whether the non-conscious processing of fearful faces exist in
      unattended condition, event-related potentials (ERPs) were recorded in a facial
      expression detection task. Participants were asked to discriminate the facial
      expressions (fearful or neutral) at the attended location. Unattended faces were
      associated with a response that was either congruent or in conflict with the
      response to the attended face. ERP results showed that the trials with response
      conflict between attended and unattended faces enhanced the amplitude of the P3
      component when the neutral face was presented at attended location and the
      fearful face was presented at the unattended location. Our findings imply that
      the non-conscious fearful faces can be processed in the unattended condition.

PMID- 22155094
TI  - Gender differences in the IL6 -174G>C and ESR2 1730G>A polymorphisms and the risk
      of Parkinson's disease.
AB  - The -174G>C (rs1800795) single nucleotide polymorphism (SNP) in the promoter of
      the interleukin-6 (IL6) gene and the 1730G>A (rs4986938) SNP in the estrogen
      receptor beta (ESR2) may influence the risk of Parkinson's disease (PD). We
      investigated these SNPs in 380 unrelated US Caucasian PD cases and 522 controls,
      including 452 individuals of Ashkenazi Jewish (AJ) origin (260 PD, 192 controls).
      The G allele of the -174G>C SNP was more common in AJ PD cases (p=0.033) as well
      as in Non-Jewish (NJ) men with PD (p=0.022). The GG genotype increased the risk
      of PD by over two fold in NJ men (OR=2.11, 95%CI: 1.14-3.89, p=0.017), and
      approached significance in the total AJ group with PD (OR=1.42, 95%CI: 0.97-2.06,
      p=0.067). The A allele of the ESR2 1730G>A SNP was associated with a decreased
      risk for PD in AJ women, and in this group, having the AA genotype decreased the
      risk of PD by half (OR=0.45, 95%CI: 0.22-0.92, p=0.029). Our data supports a role
      for the IL6 -174G>C G allele in AJ individuals overall. In NJ Caucasians, this
      role appears to be gender mediated. In both groups, the effect is independent
      from ESR2 1730G>A. A separate association for the ESR2 1730G>A SNP was found
      exclusively in women of AJ descent. Other polymorphisms in tight linkage
      disequilibrium with the SNP differentially influencing expression, ethnic
      differences in allele distribution, and gender differences in genetic load
      related to PD, may underlie our findings. Larger studies in diverse populations,
      including analysis of surrounding regions are recommended.

PMID- 22155095
TI  - Flupirtine inhibits calcitonin-gene related peptide release from rat brainstem in
      vitro.
AB  - We have previously shown that the nonopioid analgesic flupirtine possesses
      analgesic activity in the orofacial formalin test in vivo in the rat. However,
      this paradigm does not allow to distinguish between central and peripheral site
      of action of the drug. In this study we used a recently characterized in vitro
      model, consisting in acute rat brainstem explants, to investigate whether
      flupirtine analgesia may be, at least in part, attributed to interference with
      neurotransmission between the first and the second order neurons of the
      trigeminal system, occurring within the brainstem. We used acute rat brainstem
      explants; CGRP released into the incubation medium was taken as a marker of CGRP
      release from central terminals of trigeminal ganglion afferent neurons within the
      brainstem. CGRP levels were measured by radioimmunoassay under basal conditions
      or in the presence of flupirtine, alone or with putative antagonist XE-991. We
      found that flupirtine inhibits in a concentration-dependent manner both basal and
      capsaicin-stimulated CGRP release from rat brainstem. This effect is mimicked by
      the flupirtine analogue retigabine, and is counteracted by the Kv7 blocker XE
      991. These findings provide in vitro evidence that the analgesic activity of
      flupirtine may be related to interference with pain neurotransmission at the
      brainstem level. Pharmacological data suggests that such effect is related to
      opening of Kv7 channels on first-order neuronal nerve ending, and the subsequent
      inhibition of neurotransmitter release, since the effect is mimicked by the Kv7
      opener retigabine and is counteracted by the Kv7 blocker XE-991.

PMID- 22155096
TI  - Microinjection of sanguinarine into the ventrolateral orbital cortex inhibits Mkp
      1 and exerts an antidepressant-like effect in rats.
AB  - We investigated the antidepressant effects of bilateral intra-the ventrolateral
      orbital cortex (VLO) administration of sanguinarine (SA), a selective mitogen
      activated protein kinase phosphatase-1 (Mkp-1) inhibitor, in rats that had been
      subjected to a forced swimming test (FST) which is a classic animal model of
      depression. The expression of Mkp-1 and activation of ERK (ratio of phosphor-ERK
      to ERK) were also examined by immunoblotting. A single bilateral intra-VLO
      infusion of SA (2.5, 5 or 10 MUg/0.5 MUl per side) significantly reduced
      immobility time in the FST in dose-dependent fashion, as compared to vehicle
      treated controls. A similar antidepressant effect was also observed in rats
      systemically administered fluoxetine, a classic antidepressant. The effects
      observed in the FST could not be attributed to non-specific increases in activity
      as neither microinjection of SA into the VLO nor fluoxetine treatment altered the
      behavior of the rats during the locomotion test. In addition, a decrease in the
      expression of Mkp-1 and a correlative increase in ERK activation were involved in
      the antidepressant effects of the bilateral SA administration into the VLO. The
      results indicated that Mkp-1 within the VLO is involved in the process of
      depression and may be a potential target for therapeutic action of antidepressant
      treatment.

PMID- 22155097
TI  - The bile steroid chenodeoxycholate is a potent antagonist at NMDA and GABA(A)
      receptors.
AB  - The bile steroids (BS) cholic acid and chenodeoxycholic acid are produced in
      hepatocytes and in the brain. Nothing is known about neuronal actions of BS.
      Deficiency in a 27-hydroxylase enzyme coincides with reduced production of
      chenodeoxycholic acid (CDCA) and a relative increase in cholic acid in an
      inherited lipid storage disease, cerebrotendinous xanthomatosis, characterized by
      neurological dysfunctions, which can be treated by dietary CDCA. We have examined
      the modulation of hypothalamic network activity by nine common BS. Cholate and
      CDCA significantly reduced the firing of hypothalamic neurons and synchronized
      network activity with CDCA being nearly 10 times more potent. The synthetic BS
      dehydrocholate synchronized the activity without affecting the firing rate.
      Gabazine, a GABA(A) receptor antagonist, occluded synchronization by BS. Whole
      cell patch clamp recordings revealed a block of NMDA- and GABA(A)-receptors by
      BS. Potencies of nine common BS differed between NMDA and GABA(A) receptors,
      however in both cases they correlated with BS affinities for albumin but not with
      their lipophilicity, supporting a direct action at ligand gated ion channels.
      GABAergic synaptic currents displayed a faster decay under BS. Our data provide
      new insight into extrahepatic functions of BS revealing their neuroactive
      potential.

PMID- 22155098
TI  - Enriched odor exposure decrease tau phosphorylation in the rat hippocampus and
      cortex.
AB  - Abnormally hyperphosphorylated microtubule-associated protein tau is the main
      component of the neurofibrillary tangles (NFT), a hallmark pathological feature
      of Alzheimer's disease (AD). A lot of studies suggested that there is highly
      neurobiological correlation between olfactory dysfunction and AD-like pathology,
      but the effect of the odor stimulation on tau phosphorylation remains unknown.
      Here, we examined the effect of short-term and long-term enriched odor exposure
      on the alterations of tau phosphorylation at multiple sites in the rat brains. We
      found that short-term odor enrichment did not affect the phosphorylation of tau,
      while long-term odor enrichment dramatically reduce the phosphorylation level of
      tau at Ser198/199/202, Thr231, Ser396, and Ser404 sites both in the hippocampus
      and cortex. These data suggest that long-term odor exposure prevent tau
      phosphorylation and may be a new therapeutic strategy of AD.

PMID- 22155099
TI  - Berberine ameliorates COX-2 expression in rat small intestinal mucosa partially
      through PPARgamma pathway during acute endotoxemia.
AB  - Berberine hydrochloride (BBR), a plant alkaloid, has been used to treat
      intestinal inflammation or infection for years. Cyclooxygenase-2 (COX-2) is pro
      inflammatory mediator and involved in the induction of gut inflammation. The
      expression of COX-2 in small bowel mucosa was determined and the mechanism by
      which BBR modulated COX-2 expression was explored in a rat model of endotoxemia
      induced by lipopolysaccharide (LPS). The results showed that without LPS
      stimulation COX-2 was constitutively expressed at low levels in control rats. LPS
      challenge rapidly induced COX-2 gene transcription resulting in high levels of
      inducible COX-2 expression in endotoxemic rats. BBR pre- and post-treatment had
      no marked effect on constitutive COX-2 expression but inhibited inducible COX-2
      overexpression. LPS challenge increased the expression and phosphorylation of
      peroxisome proliferator-activated receptor gamma (PPARgamma), p38 and activating
      transcription factor 2 and 3 (ATF2, ATF3), but the effects of LPS were inhibited
      by BBR treatment. GW9662 did not influence constitutive COX-2 expression but
      enhanced inducible COX-2 overproduction. Besides, GW9662 abolished the inhibitory
      effect of BBR on inducible COX-2, p38, ATF2, 3 expression and phosphorylation.
      Collectively, these results indicated that BBR gavage could attenuate the
      overexpression of inducible COX-2, not constitutive COX-2, in ileal mucosa during
      acute endotoxemia in part via activation of PPARgamma pathway, which negatively
      interfered with p38/ATFs cascade.

PMID- 22155100
TI  - Ex vivo induced regulatory T cells regulate inflammatory response of Kupffer
      cells by TGF-beta and attenuate liver ischemia reperfusion injury.
AB  - In the presence of TGF-beta, CD4+CD62L+T cells can be induced to CD4+CD25+FoxP3+
      regulatory T cells (iTregs). In our previous work, we have shown that adoptive
      transfer of iTregs promoted liver recovery from ischemia reperfusion injury
      (IRI). In this study, we examined the molecular mechanism underlying the liver
      IRI attenuation by iTregs in a mouse partial hepatic IRI model. We found that the
      population of hepatic Tregs decreased significantly at 24 h after reperfusion.
      Adoptive transfer of iTregs before IRI markedly increased the numbers of hepatic
      Tregs and attenuated liver IRI as indicated by reduced serum aminotransferases
      and proinflammatory cytokines, such as interleukin-1 beta (IL-1beta) and tumor
      necrosis factor alpha (TNF-alpha). Ex vivo study indicated that iTregs suppressed
      IL-1beta and TNF-alpha expression, promoted transcription of interleukin-10 (IL
      10), and elevated phosphorylation of SMAD3 in Kupffer cells (KCs). Furthermore,
      inhibition of TGF-beta signaling by anti-TGF-beta abolished the effects on KCs.
      Treatment with TGF-beta suppressed matrix metalloprotease (MMP9) production in
      KCs and protected liver from IRI. In conclusion, our results suggest that iTregs
      play a critical role in hepatic IRI by regulating pro-inflammatory and anti
      inflammatory function of KCs through TGF-beta.

PMID- 22155101
TI  - Fluticasone propionate and Salmeterol combination induces SOCS-3 expression in
      airway epithelial cells.
AB  - Fluticasone propionate (FP) and Salmeterol (SAL) are commonly used in combination
      therapy for patients with Chronic obstructive pulmonary disease (COPD). Clinical
      studies show that FP/SAL used in combination therapy was found to inhibit airway
      inflammation in COPD patients. However, the mechanisms associated with FP/SAL
      induced anti-inflammatory effects were not clear. We have evaluated the effect of
      FP/SAL and tobacco smoke (TS) on SOCS-3 and interleukine-6 expression in
      bronchial airway epithelial cells (BAEpCs). Human BAEpCs were exposed to TS and
      subsequently treated with FP or SAL alone or in combinations in the presence and
      absence of mitogen activated protein kinase (MAPK) inhibitors for either
      Erk1/Erk2, or p38 or PI3 kinase. In BAEpCs, TS induced IL-6 expression via
      ERK1/ERK2 MAPK pathway and FP/SAL inhibited TS mediated IL-6 expression. TS down
      regulated the SOCS-3 expression via activation of Erk1/Erk2, and p38 MAPK
      signaling. When TS exposed BAEpCs were treated with FP/SAL SOCS-3 expression was
      restored. FP/SAL combinations induced significantly higher expression of SOCS-3
      in BAEpCs when compared to individual drug. Pretreatment with Ly294002 a PI3 MAPK
      inhibitor significantly attenuated FP/SAL induced SOCS-3 expression in BAEpCs.
      Furthermore, FP/SAL blunted TS induced phosphorylation of Erk1/Erk2 and p38 MAPK
      in BAEpCs. Our study suggests that TS inhibits SOCS-3, combination of FP/SAL has
      a profound synergistic effect on SOCS-3 induction in BAEpCs and it is dependent
      on PI3 kinase signaling pathway. SOCS-3 may represent a potential biomarker for
      understanding the efficacy and a novel anti-inflammatory mechanism of FP/SAL
      combination therapy in the treatment of COPD.

PMID- 22155102
TI  - Anti-inflammatory and antioxidative effects of mucilage of Trigonella foenum
      graecum (Fenugreek) on adjuvant induced arthritic rats.
AB  - The aim of this study was to investigate anti-inflammatory and antioxidant
      effects of mucilage from fenugreek in adjuvant induced arthritis in rats.
      Arthritis was induced by intradermal injection of complete Freund's adjuvant into
      the right hind paw produce inflammation of the joint. The activities of
      inflammatory enzymes like cyclooxygenase, lipoxygenase and myeloperoxidase, and
      levels of nitrite and C-reactive protein were observed. Also oxidative stress was
      measured by analyzing the activity of catalase, superoxide dismutase, glutathione
      peroxidase and the levels of glutathione and vitamin C and lipid peroxidation.
      The blood parameters like ESR, total WBC, RBC and hemoglobin content was checked.
      Fenugreek mucilage exhibited maximum percentage of edema inhibition at a dose of
      75 mg/kg on 21st day of adjuvant arthritis. The effect was higher than that of
      standard drug indomethacin. The activities of cyclooxygenase-2 and
      myeloperoxidase and concentration of thiobarbituric acid reactive substance
      (TBARS) were decreased and the activities of antioxidant enzymes, vitamins C and
      reduced glutathione level were increased on treatment with fenugreek mucilage.
      The increment in ESR and total WBC, reduction in RBC count and hemoglobin and
      aberrant changes to the C-reactive protein (CRP) levels observed in the arthritic
      animals were also found to be significantly restored in fenugreek mucilage
      treated rats. Histopathology of paw tissue showed decreased edema formation and
      cellular infiltration on supplementation with fenugreek mucilage. Thus the
      results demonstrated the potential beneficiary effect of fenugreek mucilage on
      adjuvant induced arthritis in rats.

PMID- 22155103
TI  - Saucerneol F, a new lignan, inhibits iNOS expression via MAPKs, NF-kappaB and AP
      1 inactivation in LPS-induced RAW264.7 cells.
AB  - Saucerneol F (SF), a new tetrahydrofuran-type sesquilignan isolated from Saururus
      chinensis, dose-dependently inhibited nitric oxide (NO) production, with
      concomitant reduction of inducible nitric oxide synthase (iNOS) protein and mRNA
      expression in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7
      cells. To elucidate the molecular mechanism underlying the inhibition of iNOS
      expression by SF, we assessed the effects of SF on nuclear factor-kappaB (NF
      kappaB) DNA-binding activity, NF-kappaB-dependent reporter gene activity,
      inhibitory factor-kappaB (IkappaB) phosphorylation and degradation, and p65
      nuclear translocation. Treatment with SF decreased the luciferase activities of
      NF-kappaB reporter promoters in a dose-dependent manner and translocation of NF
      kappaB p65. In addition, pretreatment of SF reduced LPS-stimulated activation of
      mitogen-activated protein kinases (MAPKs) including extracellular signal
      regulated kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun NH(2)-terminal kinase (JNK).
      Furthermore, SF attenuated the luciferase activities of AP-1 reporter promoters
      and the DNA-binding capacity of AP-1. Taken together, the present results
      indicate that SF attenuates NO production and iNOS expression by blocking LPS
      induced activation of NF-kappaB, MAPKs, and AP-1, suggesting that SF is
      potentially applicable as an anti-inflammatory drug.

PMID- 22155104
TI  - Integrative genome-wide expression and promoter DNA methylation profiling
      identifies a potential novel panel of ovarian cancer epigenetic biomarkers.
AB  - To identify epigenetic-based biomarkers for diagnosis of ovarian cancer we
      performed MeDIP-Chip in A2780 and CaOV3 ovarian cancer cell lines. Validation by
      Sequenom massARRAY methylation analysis confirmed a panel of six gene promoters
      (ARMCX1, ICAM4, LOC134466, PEG3, PYCARD & SGNE1) where hypermethylation
      discriminated 27 serous ovarian cancer clinical samples versus 12 normal ovarian
      surface epithelial cells (OSE) (ROC of 0.98). Notably, CpG sites across the
      transcription start site of a potential long-intergenic non-coding RNA (lincRNA)
      gene (LOC134466), was shown to be hypermethylated in 81% of serous EOC and could
      differentiate tumours from OSE (p<0.05). We propose that this potential biomarker
      panel holds great promise as a diagnostic test for high-grade (Type II) serous
      ovarian cancer.

PMID- 22155105
TI  - B-DIM impairs radiation-induced survival pathways independently of androgen
      receptor expression and augments radiation efficacy in prostate cancer.
AB  - Increased consumption of cruciferous vegetables is associated with decreased risk
      in prostate cancer (PCa). The active compound in cruciferous vegetables appears
      to be the self dimerized product [3,3'-diindolylmethane (DIM)] of indole-3
      carbinol (I3C). Nutritional grade B-DIM (absorption-enhanced) has proven safe in
      a Phase I trial in PCa. We investigated the anti-cancer activity of B-DIM as a
      new biological approach to improve the effects of radiotherapy for hormone
      refractory prostate cancer cells, which were either positive or negative for
      androgen receptor (AR) expression. B-DIM inhibited cell growth in a dose
      dependent manner in both PC-3 (AR-) and C4-2B (AR+) cell lines. B-DIM was
      effective at increasing radiation-induced cell killing in both cell lines,
      independently of AR expression. B-DIM inhibited NF-kappaB and HIF-1alpha DNA
      activities and blocked radiation-induced activation of these transcription
      factors in both PC-3 and C4-2B cells. In C4-2B (AR+) cells, AR expression and
      nuclear localization were significantly increased by radiation. However, B-DIM
      abrogated the radiation-induced AR increased expression and trafficking to the
      nucleus, which was consistent with decreased PSA secretion. In vivo, treatment of
      PC-3 prostate tumors in nude mice with B-DIM and radiation resulted in
      significant primary tumor growth inhibition and control of metastasis to para
      aortic lymph nodes. These studies demonstrate that B-DIM augments radiation
      induced cell killing and tumor growth inhibition. B-DIM impairs critical survival
      signaling pathways activated by radiation, leading to enhanced cell killing.
      These novel observations suggest that B-DIM could be used as a safe compound to
      enhance the efficacy of radiotherapy for castrate-resistant PCa.

PMID- 22155107
TI  - Nitrate and ammonium uptake by natural stream sediment microbial communities in
      response to nutrient enrichment.
AB  - Anthropogenic activities have increased nitrogen concentration in many
      ecosystems. Because microbes have higher metabolic rates relative to larger
      organisms, microbial activity may influence nitrogen movement and degradation
      significantly in ecosystems. Thus, the ability for microorganisms to adapt to
      increasing nitrogen concentrations is essential to ecosystem sustainability. We
      measured sediment microbial community nitrogen assimilation after sustained
      nitrogen enrichments using in vitro and isotopic techniques. Mixed-microbial
      communities were exposed to-enriched concentrations of NO(3)-N (1 mg l(-1)) and
      NH(4)-N (30 MUg l(-1)) for four weeks. Each week, filtered water samples were
      collected from each mesocosm and sediment was removed to quantify rates of
      nitrogen assimilation by the sediment microbial community. During the fourth
      week, isotopic tracers (15)NO(3) and (15)NH(4) were added to mesocosms to
      directly measure nitrogen incorporation into microbial cells as organic (15)N.
      Initial microbial responses to nitrogen enrichment were distinctly different from
      the sustained microbial community responses. NH(4)-N uptake was initially
      stimulated with NH(4)-N enrichments but increased uptake rates were not sustained
      over time. Sustained responses to changing nitrogen availability equilibrated
      within 1-3 weeks (depending on nitrogen form), indicating that even though
      microbial communities can respond to increased availability, potential for
      increased assimilation is limited.

PMID- 22155106
TI  - Lactobacillus fermentum CECT 5716 is safe and well tolerated in infants of 1-6
      months of age: a randomized controlled trial.
AB  - The objective of the study was to evaluate the safety and tolerance of an infant
      formula supplemented with Lactobacillus fermentum CECT5716, a probiotic strain
      isolated from breast milk, in infants of 1-6 months of age. A randomized double
      blinded controlled study including healthy infants was conducted. One month aged
      infants received a prebiotic infant formula supplemented with L. fermentum
      (experimental group) or the same formula without the probiotic strain (control
      group) for 5 months. The primary outcome of the study was average daily weight
      gain between baseline and 4 months of age. Secondary outcomes were other
      anthropometric data (length and head circumference), formula consumption, and
      tolerance. Incidence of infections was also recorded by pediatricians. No
      significant differences in weight gain were observed between both groups, neither
      at 4 months of age (29.0+/-7.8 vs 28.9+/-5.7g/day) nor at 6 months (25.1+/-6.1 vs
      24.7+/-5.2g/day). There were no statistically significant differences in the
      consumption of the formulae or symptoms related to the tolerance of the formula.
      The incidence rate of gastrointestinal infections in infants of the control group
      was 3 times higher than in the probiotic group (p=0.018). Therefore, consumption
      of a prebiotic infant formula enriched with the human milk probiotic strain L.
      fermentum CECT5716 from 1 to 6 months of life is well tolerated and safe.
      Furthermore, the consumption of this formula may improve the health of the
      infants by reducing the incidence of gastrointestinal infections.

PMID- 22155108
TI  - A novel population of cells expressing both hematopoietic and mesenchymal markers
      is present in the normal adult bone marrow and is augmented in a murine model of
      marrow fibrosis.
AB  - Bone marrow (BM) fibrosis is a feature of severe hyperparathyroidism. Consistent
      with this observation, mice expressing constitutively active parathyroid hormone
      (PTH)/PTH-related peptide receptors (PPR) in osteoblasts (PPR*Tg) display BM
      fibrosis. To obtain insight into the nature of BM fibrosis in such a model, a
      double-mutant mouse expressing constitutively active PPR and green fluorescent
      protein (GFP) under the control of the type I collagen promoter (PPR*Tg/GFP) was
      generated. Confocal microscopy and flow cytometry revealed the presence of a cell
      population expressing GFP (GFP(+)) that was also positive for the hematopoietic
      marker CD45 in the BM of both PPR*Tg/GFP and control animals. This cell
      population was expanded in PPR*Tg/GFP. The existence of cells expressing both
      type I collagen and CD45 in the adult BM was confirmed by IHC and fluorescence
      activated cell sorting. An analysis of total RNA extracted from sorted
      GFP(+)CD45(+) cells showed that these cells produced type I collagen and PTH/PTH
      related peptide receptor and receptor activator for NF-kappaB mRNAs, further
      supporting their features of being both mesenchymal and hematopoietic lineages.
      Similar cells, known as fibrocytes, are also present in pathological fibroses.
      Our findings, thus, indicate that the BM is a permissive microenvironment for the
      differentiation of fibrocyte-like cells and raise the possibility that these
      cells could contribute to the pathogenesis of BM fibrosis.

PMID- 22155109
TI  - Probiotic bacteria induce maturation of intestinal claudin 3 expression and
      barrier function.
AB  - An immature intestinal epithelial barrier may predispose infants and children to
      many intestinal inflammatory diseases, such as infectious enteritis, inflammatory
      bowel disease, and necrotizing enterocolitis. Understanding the factors that
      regulate gut barrier maturation may yield insight into strategies to prevent
      these intestinal diseases. The claudin family of tight junction proteins plays an
      important role in regulating epithelial paracellular permeability. Previous
      reports demonstrate that rodent intestinal barrier function matures during the
      first 3 weeks of life. We show that murine paracellular permeability markedly
      decreases during postnatal maturation, with the most significant change occurring
      between 2 and 3 weeks. Here we report for the first time that commensal bacterial
      colonization induces intestinal barrier function maturation by promoting claudin
      3 expression. Neonatal mice raised on antibiotics or lacking the toll-like
      receptor adaptor protein MyD88 exhibit impaired barrier function and decreased
      claudin 3 expression. Furthermore, enteral administration of either live or heat
      killed preparations of the probiotic Lactobacillus rhamnosus GG accelerates
      intestinal barrier maturation and induces claudin 3 expression. However, live
      Lactobacillus rhamnosus GG increases mortality. Taken together, these results
      support a vital role for intestinal flora in the maturation of intestinal barrier
      function. Probiotics may prevent intestinal inflammatory diseases by regulating
      intestinal tight junction protein expression and barrier function. The use of
      heat-killed probiotics may provide therapeutic benefit while minimizing adverse
      effects.

PMID- 22155110
TI  - The influence of skeletal muscle on the regulation of liver:body mass and liver
      regeneration.
AB  - The relationship between liver and body mass is exemplified by the precision with
      which the liver:body mass ratio is restored after partial hepatic resection.
      Nevertheless, the compartments, against which liver mass is so exquisitely
      regulated, currently remain undefined. In the studies reported here, we
      investigated the role of skeletal muscle mass in the regulation of liver:body
      mass ratio and liver regeneration via the analysis of myostatin-null mice, in
      which skeletal muscle is hypertrophied. The results showed that liver mass is
      comparable and liver:body mass significantly diminished in the null animals
      compared to age-, sex-, and strain-matched controls. In association with these
      findings, basal hepatic Akt signaling is decreased, and the expression of the
      target genes of the constitutive androstane receptor and the integrin-linked
      kinase are dysregulated in the myostatin-null mice. In addition, the baseline
      expression levels of the regulators of the G1-S phase cell cycle progression in
      liver are suppressed in the null mice. The initiation of liver regeneration is
      not impaired in the null animals, although it progresses toward the lower
      liver:body mass set point. The data show that skeletal muscle is not the body
      component against which liver mass is positively regulated, and thus they
      demonstrate a previously unrecognized systemic compartmental specificity for the
      regulation of liver:body mass ratio.

PMID- 22155111
TI  - Gsdma3 mutation causes bulge stem cell depletion and alopecia mediated by skin
      inflammation.
AB  - Primary cicatricial alopecias (PCAs) are a group of permanent hair loss
      disorders, of which the pathogenesis is still poorly understood. The alopecia and
      excoriation (AE) mouse strain is a dominant mutant generated from ethyl
      nitrosourea mutagenesis. AE mice exhibit a progressive alopecia phenotype similar
      to that seen in PCAs, resulting from a point mutation in the gasdermin A3 gene.
      Mutant mice begin to show alopecia on the head from postnatal day 22 and
      experience complete hair loss by the age of 6 months, along with hyperkeratosis
      and catagen delay. The results of a histological examination showed that bulge
      stem cells in AE skin are gradually depleted, as indicated by decreased keratin
      15 and CD34 expression, and reduced bromodeoxyuridine label-retaining cells in
      the AE bulge. In addition, AE mice display an inflammatory condition in the skin
      from postnatal day 7, including elevated tumor necrosis factor-alpha and monocyte
      chemotactic protein-1 mRNA levels and significantly increased macrophages and
      dendritic cell number. Immune privilege in the bulge was also compromised in AE
      skin. Consistently, after treatment with the immunosuppressive agent,
      cyclosporine A, immune privilege collapse, stem cell destruction, and alopecia
      phenotype of AE mice were all rescued. Collectively, our data demonstrate that
      immune-mediated destruction of bulge stem cells plays a crucial role in the
      pathogenesis of alopecia in AE mice, and this strain might be an interesting
      model for PCAs, especially for lichen planopilaris.

PMID- 22155113
TI  - Effects of long distance transportation and CO2 stunning on critical blood values
      in pigs.
AB  - The aim of the study was to evaluate the effect of two stressful stimuli, long
      transportation and 80% CO(2) stunning on metabolic-physiological variables,
      hemodynamic and gas exchange in slaughter pigs imported from the U.S. to Mexico
      City with a journey time of 27 h, with 8 h of lairage at the abattoir. A total of
      589 pigs from three genders were monitored. Overall results show that both
      stimuli caused metabolic and physiological disturbance. Gilts were more efficient
      in controlling glycemia after a long transport journey (24h), than castrated
      males (P<0.05), whose glucose was increased above the 30 mg/dL basal level.
      Females on arrival had 23mg/dL more lactate compared to basal levels (P<0.05).
      Stunning caused more physiological effects compared to transportation. Regarding
      the gender factor, females and entire males were more susceptible to transport
      stress and stunning compared to the castrated pigs, and entire males showed more
      complications restoring the gas exchange compared to females and barrows.

PMID- 22155112
TI  - The endocannabinoid system and plant-derived cannabinoids in diabetes and
      diabetic complications.
AB  - Oxidative stress and inflammation play critical roles in the development of
      diabetes and its complications. Recent studies provided compelling evidence that
      the newly discovered lipid signaling system (ie, the endocannabinoid system) may
      significantly influence reactive oxygen species production, inflammation, and
      subsequent tissue injury, in addition to its well-known metabolic effects and
      functions. The modulation of the activity of this system holds tremendous
      therapeutic potential in a wide range of diseases, ranging from cancer, pain,
      neurodegenerative, and cardiovascular diseases to obesity and metabolic syndrome,
      diabetes, and diabetic complications. This review focuses on the role of the
      endocannabinoid system in primary diabetes and its effects on various diabetic
      complications, such as diabetic cardiovascular dysfunction, nephropathy,
      retinopathy, and neuropathy, particularly highlighting the mechanisms beyond the
      metabolic consequences of the activation of the endocannabinoid system. The
      therapeutic potential of targeting the endocannabinoid system and certain plant
      derived cannabinoids, such as cannabidiol and Delta9-tetrahydrocannabivarin,
      which are devoid of psychotropic effects and possess potent anti-inflammatory
      and/or antioxidant properties, in diabetes and diabetic complications is also
      discussed.

PMID- 22155114
TI  - Natural variation in the molecular stress network correlates with a behavioural
      syndrome.
AB  - In several species, individuals from the same population behave differently from
      each other. A functional link between variation in personality traits and the
      stress response has been suggested by studies in artificial selection lines in
      fish, birds and mammals. The aim of this study was to test whether the expression
      of genes involved in the stress response co-varies with personality traits in a
      natural population. Four personality traits, excreted cortisol level and brain
      expression of six candidate genes (CRF, CRF-R2, POMC1, GR1, GR2, MR) were
      measured in non-stressed wild-caught threespine sticklebacks (Gasterosteus
      aculeatus). We found correlations between variation in personality traits and
      variation in the expression of genes involved in the stress response.
      Aggressiveness was negatively correlated with cortisol levels. Boldness and
      aggressiveness formed a behavioural syndrome and were both positively correlated
      with brain expression of glucocorticoid receptors (GR1 and GR2). Boldness and
      exploration were positively correlated with expression of POMC1 but not with each
      other. Our results are compatible with a model that suggests that the
      aggressiveness-boldness behavioural syndrome could be the consequence of a
      physiological pleiotropic effect of glucocorticoid receptors, which are involved
      in the stress response and behaviour variation.

PMID- 22155115
TI  - Ser-796 of beta-galactosidase (Escherichia coli) plays a key role in maintaining
      a balance between the opened and closed conformations of the catalytically
      important active site loop.
AB  - A loop (residues 794-803) at the active site of beta-galactosidase (Escherichia
      coli) opens and closes during catalysis. The alpha and beta carbons of Ser-796
      form a hydrophobic connection to Phe-601 when the loop is closed while a
      connection via two H-bonds with the Ser hydroxyl occurs with the loop open. beta
      Galactosidases with substitutions for Ser-796 were investigated. Replacement by
      Ala strongly stabilizes the closed conformation because of greater hydrophobicity
      and loss of H-bonding ability while replacement with Thr stabilizes the open form
      through hydrophobic interactions with its methyl group. Upon substitution with
      Asp much of the defined loop structure is lost. The different open-closed
      equilibria cause differences in the stabilities of the enzyme.substrate and
      enzyme.transition state complexes and of the covalent intermediate that affect
      the activation thermodynamics. With Ala, large changes of both the
      galactosylation (k(2)) and degalactosylation (k(3)) rates occur. With Thr and
      Asp, the k(2) and k(3) were not changed as much but large DeltaH(?) and
      TDeltaS(?) changes showed that the substitutions caused mechanistic changes.
      Overall, the hydrophobic and H-bonding properties of Ser-796 result in
      interactions strong enough to stabilize the open or closed conformations of the
      loop but weak enough to allow loop movement during the reaction.

PMID- 22155116
TI  - Racial and ethnic disparities in the use of intravenous recombinant tissue
      plasminogen activator and outcomes for acute ischemic stroke.
AB  - Racial and ethnic disparities in acute stroke care in the United States have been
      previously reported. This study investigated possible racial and ethnic
      disparities in the administration and outcome of recombinant tissue plasminogen
      activator (rtPA) therapy for acute ischemic stroke in whites, blacks, Hispanics,
      and Asian/Pacific Islanders. Using the National Inpatient Sample for 2001-2008,
      we selected patients with a primary diagnosis of acute ischemic stroke who
      received treatment with rtPA. Patient data were stratified by race (white, black,
      Hispanic, and Asian/Pacific Islander). We analyzed the association of patient
      race on rtPA utilization rate, in-hospital morbidity (ie, discharge to long-term
      facility), intracranial hemorrhage (ICH) rate, and in-hospital mortality. We
      performed a multivariate logistic regression analysis to determine independent
      predictors of poor outcomes. White patients had a higher rate of tPA utilization
      than black and Hispanic patients (2.3% vs 1.8% and 2.0%, respectively; P < .0001
      for both groups). There was no difference in the rate of tPA utilization between
      whites and Asian/Pacific Islanders (2.3% vs 2.2% P = .07). Multivariate analysis
      of morbidity, mortality, and ICH rates found that Asian/Pacific Islanders had
      significantly higher rates of mortality (odds ratio, 1.22, 95% confidence
      interval, 1.03-1.44; P = .02) and ICH (odds ratio, 2.01; 95% confidence interval,
      1.91-2.11; P < .0001) compared with whites. rtPA utilization was greater in white
      and Asian/Pacific Islander patients than in black and Hispanic patients.
      Asian/Pacific Islander race was associated with increased risk of ICH and
      mortality after rtPA administration.

PMID- 22155117
TI  - Emergent angioplasty and stent placement recanalization without thrombolysis in
      acute middle cerebral artery occlusions.
AB  - A significant proportion of patients with infarcts from large-vessel lesions have
      shown a poor response to systemic thrombolysis. Stents have been used to
      recanalize occluded or severely stenosed intracranial arteries in patients with
      acute stroke. This study evaluated the feasibility, efficacy, and safety of
      intracranial artery recanalization for acute middle cerebral artery (MCA)
      occlusion using emergent angioplasty and stent placement without thrombolysis.
      All patients from a retrospectively collected database who met the inclusion
      criteria and were treated with an intracranial stent for acute MCA occlusion were
      included. Treatment comprised angioplasty and stenting without interventional
      thrombolytic therapy. Recanalization was assessed by angiography immediately
      after stent placement based on the Thrombolysis in Myocardial Infarction (TIMI)
      score. Complications related to the procedure and outcomes were assessed.
      Neurologic status was evaluated before and after treatment. Eleven patients were
      treated with emergent angioplasty and stent placement. Partial or complete
      recanalization (TIMI 2 and 3) was achieved in 11 patients (100%) assessed by
      digital subtraction angiography immediately after MCA stenting. One patient died
      due to reocclusion of MCA 2 days after the procedure. Among the survivors, 7
      patients (70%) had a good outcome (modified Rankin Scale score, 0-2) and 3
      patients (30%) had a moderate outcome (modified Rankin Scale score, 3). Follow-up
      computed tomography angiography or magnetic resonance angiography revealed mild
      restenosis in 2 of the 10 patients. This preliminary experience demonstrates the
      technical feasibility and high rate of recanalization with emergent angioplasty
      and stenting without thrombolysis in patients with acute MCA occlusion.

PMID- 22155118
TI  - Biomarker responses and genotoxicity in the mud snail (Bullacta exarata) as
      indicators of coastal contamination.
AB  - In the present study different biomarker responses and genotoxicity were
      determined in wild mud snails (Bullacta exarata) collected from 3 sampling sites
      in Bohai Bay in northeastern China, which is a region that is under considerable
      anthropogenic influence. Significant spatial variability of superoxide dismutase
      (SOD) and metallothionein (MT)-like proteins were recorded, while glutathione
      transferase (GST), catalase (CAT), and vitellin-like proteins (Vn's) were not
      observed. Furthermore, genomic DNA that was amplified with 4 fluorescence-labeled
      primer pairs showed variable genetic distances among the 3 wild mud snail
      populations found in Bohai Bay, which may be correlated with differences in the
      types of environmental genotoxicants, such as heavy metals and polycyclic
      aromatic hydrocarbons. This multi-biomarker approach provided an improved
      understanding of the potential toxicological impact of contaminated sediments on
      benthic organisms.

PMID- 22155119
TI  - Organotin levels in Nazare canyon (west Iberian Margin, NE Atlantic) and adjacent
      coastal area.
AB  - Organotin compounds (OTs) are ubiquitous in the marine environment and high
      concentrations (MUg g(-1) range) in sediments from different coastal areas around
      the world have been reported. However, few reports have described the OTs
      contamination status in the offshore and deep sea environment. This work
      investigated organotin levels in Nazare canyon for the first time. Levels of
      monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT), diphenyltin (DPT),
      triphenyltin (TPT), dioctyltin (DOT) and trioctyltin (TOT) were quantified in
      sediment samples from the upper flanks of the canyon and from the adjacent
      coastal area. TBT levels detected in the canyon flanks are about two to three
      orders of magnitude lower than those found in the coastal area. Nevertheless,
      when quantifiable, TBT levels in the canyon samples were higher than the
      Environmental Assessment Criteria set for TBT in sediments by the OSPAR
      Commission indicating that at those locations negative ecological impacts are
      likely to occur.

PMID- 22155120
TI  - Improved water quality in response to pollution control measures at Masan Bay,
      Korea.
AB  - The total pollution load management system (TPLMS) was first applied in 2007 to
      the highly developed Masan Bay watershed, Korea. To evaluate the effect of TPLMS
      on water quality improvement, we analyzed the water qualities in rivers and bay
      during 2005-2010, targeting chemical oxygen demand (COD), suspended sediment
      (SS), total nitrogen (TN), and total phosphorus (TP) loads. Land-based pollutant
      loading all decreased during this period, with a significant reduction in COD and
      SS loads (p<0.01). The COD reduction in seawater, following the TPLMS
      implementation, was also significant (p<0.01). Time-lagged responses in COD and
      Chl-a supported an estimated seawater residence time of ~1 month. Land-based
      nutrient loads were also significantly reduced for TN (p<0.01) and TP (p<0.05),
      however, significant reductions were not observed in the bay, indicating
      potential alternative nutrient inputs from non-point sources into the bay system.

PMID- 22155121
TI  - Recommendations for reporting treatment of aortic graft infections.
AB  - The purpose of these recommendations is to provide a standard format for
      reporting treatment results and standardised epidemiologic data after aortic
      vascular graft infection to improve the comparison of clinical outcomes between
      different therapeutic approaches and different study populations. Analytical
      reporting standards for patients' characteristics, type and extent of the
      disease, type of treatment and study design are described. Adherence to these
      recommendations will improve clinical relevance, quality and comparability of
      future studies dealing with aortic vascular graft infections.

PMID- 22155122
TI  - Response to Tonsaker et al.

PMID- 22155123
TI  - Cytogenetic and microtubule array effects of the zineb-containing commercial
      fungicide formulation Azzurro((r)) on meristematic root cells of Allium cepa L.
AB  - Zineb [ethylene bis(dithiocarbamate) zinc] is a widely employed foliar fungicide
      for agricultural and industrial applications. Allium cepa L. is a reliable model
      for the assessment of xenobiotic genotoxicity and cytotoxicity. We evaluated the
      effects of the zineb-containing commercial formulation Azzurro((r)) (70% zineb)
      in cell cycle stages of the meristem root cells of A. cepa. The mitotic index
      (MI), chromosomal aberrations at anaphase/telophase (CAs), micronuclei (MN), and
      abnormalities in immunodetected microtubule structures, e.g., preprophasic band
      (PPB), mitotic spindle (MS), and phragmoplast (Phrag), were used as end-points.
      Azzurro((r)) (1 and 10MUg/ml) induced a significant increase in the frequency of
      CAs (P<0.05), and the higher concentration inhibited the MI (P<0.05) compared to
      control values. The frequency of MN did not differ from control values at any
      concentration. Treatment with 1MUg/ml Azzurro((r)) induced a significant increase
      in the frequency of abnormal PPB (P<0.01), MS (P<0.001), and Phrag (P<0.01) and,
      at 10MUg/ml, enhancements in the frequencies of abnormal MS (P<0.05) and Phrag
      (P<0.05) were seen. A tubulin immunodetection assay showed that exposure to
      Azzurro((r)) interferes with normal assembly of microtubule structures during
      mitosis.

PMID- 22155124
TI  - Assessment of the in vivo genotoxicity of isomers of dinitrotoluene using the
      alkaline Comet and peripheral blood micronucleus assays.
AB  - Dinitrotoluene (DNT) is a nitroaromatic explosive that exists as six isomers; two
      major isomers (2,4- and 2,6-DNT) and four minor isomers (2,3-, 2,5-, 3,4-, and
      3,5-DNT). DNT has been found in soil, surface water, and groundwater near
      ammunition production plants. The major isomers of DNT are classified as "likely
      to cause cancer in humans."In vitro studies have provided conflicting data
      regarding the genotoxicity of the minor isomers. Studies indicate that metabolism
      in the gut and liver are necessary to convert DNT to genotoxic compounds. As
      such, in the present study the genotoxicity of isomers of DNT was assessed using
      two in vivo genotoxicity assays. The Comet assay was used to detect DNA damage in
      liver cells from male Sprague-Dawley rats following oral exposure (14-day) to
      individual isomers of DNT. The micronucleus assay was conducted using flow
      cytometric analysis to detect chromosomal damage in peripheral blood. Treatment
      with 2,3-, 3,4-, 2,4-, 2,5- and 3,5-DNT did not induce DNA damage in liver cells
      or increase the frequency of micronucleated reticulocytes (MN-RET) in peripheral
      blood at the doses tested. Treatment with 2,6-DNT induced DNA damage in liver
      tissue at all doses tested, but did not increase the frequency of micronucleated
      reticulocytes (MN-RET) in peripheral blood. Thus, 2,4-DNT and the minor isomers
      were not genotoxic under these test conditions, while 2,6-DNT was genotoxic in
      the target tissue, the liver. These results support previous research which
      indicated that the hepatocarcinogenicity of technical grade DNT (TG-DNT) could be
      attributed to the 2,6-DNT isomer.

PMID- 22155125
TI  - Tissue-specific mutagenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine as the basis
      for urothelial carcinogenesis.
AB  - Bladder cancer is one of the few cancers that have been linked to carcinogens in
      the environment and tobacco smoke. Of the carcinogens tested in mouse chemical
      carcinogenesis models, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is one that
      reproducibly causes high-grade, invasive cancers in the urinary bladder, but not
      in any other tissues. However, the basis for such a high-level tissue-specificity
      has not been explored. Using mutagenesis in lacI (Big BlueTM) mice, we show here
      that BBN is a potent mutagen and it causes high-level of mutagenesis specifically
      in the epithelial cells (urothelial) of the urinary bladder. After a 2-6-week
      treatment of 0.05% BBN in the drinking water, mutagenesis in urothelial cells of
      male and female mice was about two orders of magnitude greater than the
      spontaneous mutation background. In contrast, mutagenesis in smooth muscle cells
      of the urinary bladder was about five times lower than in urothelial tissue. No
      appreciable increase in mutagenesis was observed in kidney, ureter, liver or
      forestomach. In lacI (Big BlueTM) rats, BBN mutagenesis was also elevated in
      urothelial cells, albeit not nearly as profoundly as in mice. This provides a
      potential explanation as to why rats are less prone than mice to the formation of
      aggressive form of bladder cancer induced by BBN. Our results suggest that the
      propensity to BBN-triggered mutagenesis of urothelial cells underlies its
      heightened susceptibility to this carcinogen and that mutagenesis induced by BBN
      represents a novel model for initiation of bladder carcinogenesis.

PMID- 22155126
TI  - Proteome analysis of Acetobacter pasteurianus during acetic acid fermentation.
AB  - Acetic acid bacteria (AAB) are Gram-negative, strictly aerobic microorganisms
      that show a unique resistance to ethanol (EtOH) and acetic acid (AcH). Members of
      the Acetobacter and Gluconacetobacter genera are capable of transforming EtOH
      into AcH via the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)
      enzymes and are used for the industrial production of vinegar. Several mechanisms
      have been proposed to explain how AAB resist high concentrations of AcH, such as
      the assimilation of acetate through the tricarboxylic acid (TCA) cycle, the
      export of acetate by various transporters and modifications of the outer
      membrane. However, except for a few acetate-specific proteins, little is known
      about the global proteome responses to AcH. In this study, we used 2D-DIGE to
      compare the proteome of Acetobacter pasteurianus LMG 1262(T) when growing in
      glucose or ethanol and in the presence of acetic acid. Interesting protein spots
      were selected using the ANOVA p-value of 0.05 as threshold and 1.5-fold as the
      minimal level of differential expression, and a total of 53 proteins were
      successfully identified. Additionally, the size of AAB was reduced by
      approximately 30% in length as a consequence of the acidity. A modification in
      the membrane polysaccharides was also revealed by PATAg specific staining.

PMID- 22155127
TI  - Development of a Protein Standard Absolute Quantification (PSAQTM) assay for the
      quantification of Staphylococcus aureus enterotoxin A in serum.
AB  - Enterotoxin A (SEA) is a staphylococcal virulence factor which is suspected to
      worsen septic shock prognosis. However, the presence of SEA in the blood of
      sepsis patients has never been demonstrated. We have developed a mass
      spectrometry-based assay for the targeted and absolute quantification of SEA in
      serum. To enhance sensitivity and specificity, we combined an immunoaffinity
      based sample preparation with mass spectrometry analysis in the selected reaction
      monitoring (SRM) mode. Absolute quantification of SEA was performed using the
      PSAQTM method (Protein Standard Absolute Quantification), which uses a full
      length isotope-labeled SEA as internal standard. The lower limit of detection
      (LLOD) and lower limit of quantification (LLOQ) were estimated at 352pg/mL and
      1057pg/mL, respectively. SEA recovery after immunocapture was determined to be
      7.8+/-1.4%. Therefore, we assumed that less than 1femtomole of each SEA
      proteotypic peptide was injected on the liquid chromatography column before SRM
      analysis. From a 6-point titration experiment, quantification accuracy was
      determined to be 77% and precision at LLOQ was lower than 5%. With this sensitive
      PSAQ-SRM assay, we expect to contribute to decipher the pathophysiological role
      of SEA in severe sepsis. This article is part of a Special Issue entitled:
      Proteomics: The clinical link.

PMID- 22155128
TI  - Extreme diversity of scorpion venom peptides and proteins revealed by
      transcriptomic analysis: implication for proteome evolution of scorpion venom
      arsenal.
AB  - Venom is an important genetic development crucial to the survival of scorpions
      for over 400 million years. We studied the evolution of the scorpion venom
      arsenal by means of comparative transcriptome analysis of venom glands and
      phylogenetic analysis of shared types of venom peptides and proteins between
      buthids and euscorpiids. Fifteen types of venom peptides and proteins were
      sequenced during the venom gland transcriptome analyses of two Buthidae species
      (Lychas mucronatus and Isometrus maculatus) and one Euscorpiidae species
      (Scorpiops margerisonae). Great diversity has been observed in translated amino
      acid sequences of these transcripts for venom peptides and proteins. Seven types
      of venom peptides and proteins were shared between buthids and euscorpiids.
      Molecular phylogenetic analysis revealed that at least five of the seven common
      types of venom peptides and proteins were likely recruited into the scorpion
      venom proteome before the lineage split between Buthidae and Euscorpiidae with
      their corresponding genes undergoing individual or multiple gene duplication
      events. These are alpha-KTxs, betaKSPNs (beta-KTxs and scorpines), anionic
      peptides, La1-like peptides, and SPSVs (serine proteases from scorpion venom).
      Multiple types of venom peptides and proteins were demonstrated to be
      continuously recruited into the venom proteome during the evolution process of
      individual scorpion lineages. Our results provide an insight into the recruitment
      pattern of the scorpion venom arsenal for the first time.

PMID- 22155129
TI  - Macrophage-capping protein as a tissue biomarker for prediction of response to
      gemcitabine treatment and prognosis in cholangiocarcinoma.
AB  - Cholangiocarcinoma is one of the deadliest malignancies worldwide. Recent studies
      reported that treatment with gemcitabine was effective in prolonging survival.
      However, as the treatment only benefited a limited subset of patients, selection
      of patients before treatment is required. To discover biomarkers predictive of
      the response to gemcitabine treatment in cholangiocarcinoma, we examined the
      proteome of three types of material resource; ten cell lines, nine xenografts and
      nine surgically resected primary tumors from patients who exhibited different
      response to gemcitabine treatment. Two-dimensional difference gel electrophoresis
      generated quantitative protein expression profiles including 3571 protein spots.
      We detected 172 protein spots with significant correlation with response to
      gemcitabine treatment. All proteins corresponding to these 172 protein spots were
      identified by mass spectrometry. We found that the macrophage-capping protein
      (CapG) was associated with response to gemcitabin treatment in all three types of
      material source. Immunohistochemical validation in an additional set of 196
      cholangiocarcinoma cases revealed that CapG expression was associated with
      lymphatic invasion status and overall survival. Multivariate analysis showed that
      CapG protein expression was an independent prognostic factor for overall
      survival. In conclusion, CapG was identified as a novel candidate biomarker to
      predict response to gemcitabine treatment and survival in cholangiocarcinoma.

PMID- 22155130
TI  - Cohesin and chromatin organisation.
AB  - Cohesin defines the topology of chromosomes in mitosis and meiosis by holding
      sister chromatids together; more recently a role for cohesin in chromatin
      organisation and gene expression in interphase has emerged.

PMID- 22155131
TI  - Effect of new antimicrobial agents on the ecological balance of human microflora.
AB  - The human normal microflora is relatively stable at each ecological habitat under
      normal circumstances and acts as a barrier against colonization by potentially
      pathogenic microorganisms and against overgrowth of already present opportunistic
      microorganisms. Administration of antimicrobial agents causes disturbances in the
      ecological balance between the host and the normal microflora. The risk of
      emergence and spread of resistant strains between patients and dissemination of
      resistant determinants between microorganisms is reduced if colonization
      resistance is not disturbed by antimicrobial agents. In this article, the
      potential ecological effects of administration of new antimicrobial agents on the
      intestinal and oropharyngeal microflora are summarized. The review is based on
      clinical studies published during the past 10 years.

PMID- 22155132
TI  - Gene susceptibility to oxidative damage: from single nucleotide polymorphisms to
      function.
AB  - Oxidative damage to DNA can cause mutations, and mutations can lead to cancer.
      DNA repair of oxidative damage should therefore play a pivotal role in defending
      humans against cancer. This is exemplified by the increased risk of colorectal
      cancer of patients with germ-line mutations of the oxidative damage DNA
      glycosylase MUTYH. In contrast to germ-line mutations in DNA repair genes, which
      cause a strong deficiency in DNA repair activity in all cell types, the role of
      single nucleotide polymorphisms (SNPs) in sporadic cancer is unclear also because
      deficiencies in DNA repair, if any, are expected to be much milder. Further
      slowing down progress are the paucity of accurate and reproducible functional
      assays and poor epidemiological design of many studies. This review will focus on
      the most common and widely studied SNPs of oxidative DNA damage repair proteins
      trying to bridge the information available on biochemical and structural features
      of the repair proteins with the functional effects of these variants and their
      potential impact on the pathogenesis of disease.

PMID- 22155133
TI  - Modelling acidosis and the cell cycle in multicellular tumour spheroids.
AB  - A partial differential equation model is developed to understand the effect that
      nutrient and acidosis have on the distribution of proliferating and quiescent
      cells and dead cell material (necrotic and apoptotic) within a multicellular
      tumour spheroid. The rates of cell quiescence and necrosis depend upon the local
      nutrient and acid concentrations and quiescent cells are assumed to consume less
      nutrient and produce less acid than proliferating cells. Analysis of the
      differences in nutrient consumption and acid production by quiescent and
      proliferating cells shows low nutrient levels do not necessarily lead to
      increased acid concentration via anaerobic metabolism. Rather, it is the balance
      between proliferating and quiescent cells within the tumour which is important;
      decreased nutrient levels lead to more quiescent cells, which produce less acid
      than proliferating cells. We examine this effect via a sensitivity analysis which
      also includes a quantification of the effect that nutrient and acid
      concentrations have on the rates of cell quiescence and necrosis.

PMID- 22155134
TI  - The influence of assortativity on the robustness of signal-integration logic in
      gene regulatory networks.
AB  - Gene regulatory networks (GRNs) drive the cellular processes that sustain life.
      To do so reliably, GRNs must be robust to perturbations, such as gene deletion
      and the addition or removal of regulatory interactions. GRNs must also be robust
      to genetic changes in regulatory regions that define the logic of signal
      integration, as these changes can affect how specific combinations of regulatory
      signals are mapped to particular gene expression states. Previous theoretical
      analyses have demonstrated that the robustness of a GRN is influenced by its
      underlying topological properties, such as degree distribution and modularity.
      Another important topological property is assortativity, which measures the
      propensity with which nodes of similar connectivity are connected to one another.
      How assortativity influences the robustness of the signal-integration logic of
      GRNs remains an open question. Here, we use computational models of GRNs to
      investigate this relationship. We separately consider each of the three dynamical
      regimes of this model for a variety of degree distributions. We find that in the
      chaotic regime, robustness exhibits a pronounced increase as assortativity
      becomes more positive, while in the critical and ordered regimes, robustness is
      generally less sensitive to changes in assortativity. We attribute the increased
      robustness to a decrease in the duration of the gene expression pattern, which is
      caused by a reduction in the average size of a GRN's in-components. This study
      provides the first direct evidence that assortativity influences the robustness
      of the signal-integration logic of computational models of GRNs, illuminates a
      mechanistic explanation for this influence, and furthers our understanding of the
      relationship between topology and robustness in complex biological systems.

PMID- 22155135
TI  - Evolution of ape and human mating systems.
AB  - Humans (Homo sapiens) generally form multiple-male-multiple-female groups that
      include multiple family units. This social structure is maintained because
      dominant males do not monopolize females and, thus, allow subordinate males to
      mate, and human females are not generally promiscuous. Although apes show great
      variation in mating systems, the human-type mating system is unique among
      primates. The mating systems of apes and humans have evolved in response to their
      adaptation to different ecological conditions. We created and analyzed a
      mathematical model to investigate the conditions for each type of mating system
      to evolve. We focused on the mating strategy of alpha males and the mating and
      grouping strategies of females. We defined the human-type mating system as one
      with multiple-male-multiple-female groups in which alpha males do not monopolize
      females and females are not promiscuous. We demonstrated that the human-type
      mating system could evolve when a large group is advantageous and the cost of
      female promiscuity is great. Moreover, the human- and Pan-type mating systems can
      be bistable. Our results shed light on the origin of the human family.

PMID- 22155136
TI  - Pandemic influenza vaccination: lessons learned from Latin America and the
      Caribbean.
AB  - In April 2009, the World Health Organization (WHO) reported the emergence of a
      new influenza (H1N1) virus which led to the first pandemic declaration of the
      21st century. Most countries in Latin America and the Caribbean (LAC) had a
      national preparedness plan in place at this time; however, the vaccination
      component of such plans was largely undeveloped. Nevertheless, countries were
      able to capitalize on the infrastructure of their immunization programs and
      widespread experience utilizing the seasonal influenza vaccine to prepare
      rapidly, developing H1N1 vaccination plans targeting individuals with chronic
      disease, pregnant women and health care workers, among others. In LAC vaccine was
      acquired through three mechanisms: the Pan American Health Organization's
      Revolving Fund, direct manufacturer purchase, and WHO donations. Vaccine access
      was not equitable both in quantity of vaccine available and timeless of vaccine
      availability. As of December 2010, an estimated 145 million doses had been
      administered in LAC. Despite high regional coverage, there were large variations
      in coverage at the national level; pregnant women had the lowest coverage,
      despite their high risk for morbidity and mortality. The number of severe adverse
      events reported in LAC was similar to those expected with the seasonal influenza
      vaccine. Risk communication was one of the key challenges countries faced, mainly
      due to concerns and misinformation spread regarding vaccine safety. Countries and
      the international community need to learn from the experiences gained during H1N1
      vaccination in order to be better prepared for the next pandemic.

PMID- 22155137
TI  - Neuromuscular activity of Bothrops alcatraz snake venom in chick biventer
      cervicis preparations.
AB  - Venom (10-100 MUg/ml) from Bothrops alcatraz, a pitviper from the Alcatrazes
      Archipelago off the coast of southeastern Brazil, caused progressive,
      irreversible neuromuscular blockade in chick isolated biventer cervicis
      preparations. The venom also inhibited contractures to exogenous ACh (110 MUM)
      and KCl (20 mM), caused myofiber damage and increased creatine kinase release.
      Commercial bothropic antivenom raised against mainland Bothrops species
      neutralized the neuromuscular activity, depending on the venom concentration.

PMID- 22155138
TI  - Role of glutamate in coupling between bilaterally paired circadian clocks in
      Bulla gouldiana.
AB  - A group of electrically coupled basal retinal neurons (BRN) in the eye of the
      marine snail Bulla gouldiana generate a circadian rhythm in the frequency of
      compound action potentials (CAPs). CAPs are conducted to the contralateral retina
      via the optic nerves and the cerebral commissures to synchronize the rhythms of
      both eyes. CAPs can induce an excitatory postsynaptic potential (EPSP) in the
      contralateral BRNs that can lead to action potential generation. The pathway and
      mechanism of this bilateral coupling signal have not been elucidated, but the
      evidence suggests monosynaptic connections between the populations of pacemaker
      cells in both retinae. The study was designed to further characterize the
      coupling signal and investigate the role of glutamate as a neurotransmitter in
      this pathway. We found evidence supporting our hypothesis that glutamate,
      previously identified in BRNs by an immunocytological study, is involved in
      bilateral coupling. First, a combination of extracellular and intracellular
      electrophysiological recordings revealed that both electrically and optically
      evoked CAPs generate excitatory synaptic potentials and action potentials in
      contralateral BRNs. Application of glutamate also led to increased neuronal
      activity of individual BRNs both in the intact retina as well when isolated in
      cell culture. Lastly, glutamate-induced inward currents were characterized in
      cultured BRNs using perforated-patch recordings. The reversal potential was close
      to 0 mV, and the currents were sensitive to N-methyl-d-aspartic acid (NMDA) and
      non-NMDA antagonists. NMDA and AMPA, as well as aspartate, also induced distinct
      inward currents in BRNs. We conclude that glutamate can be used by BRNs as a
      transmitter to influence electrical activity in the contralateral pacemaker
      population. We propose that glutamate is required for synchronizing of the
      bilaterally paired retinal clocks producing a unified circadian timing signal.

PMID- 22155139
TI  - NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric
      Hematopoietic Cell Transplantation: health-related quality of life, functional,
      and neurocognitive outcomes.
AB  - The purpose of this manuscript is to summarize issues relevant to health-related
      quality of life (HRQL), physical function, and neurocognitive function for
      survivors of pediatric hematopoietic stem cell transplantation (HCT). The
      physiologic and psychological demands of HCT and its sequelae have the potential
      to substantially alter HRQL. When compared with research on adult HCT recipients,
      research in pediatric HRQL following HCT has lagged considerably. Initially, this
      lag was because of limited validated questionnaires, small numbers of affected
      patients, and a general lack of salience for the topic relative to traditional
      endpoints, such as transplant-related toxicity and potential mortality. The
      percentage of childhood HCT survivors with physical disability ranges from 7% to
      17% in studies where the outcome was based on clinician or self-report measures,
      to over 40% in studies where the outcome was based on a directly measured
      physical performance task. Direct and comprehensive measures of physical
      performance may help further clarify the proportion of individuals who have
      subclinical problems amenable to intervention before apparent functional loss
      becomes a problem. There is a need to include longer term survivors in such an
      assessment. In terms of neurocognitive function, the majority of reports
      demonstrate relatively good function in survivors. However, it is clear that
      little or no data on outcomes beyond 5 years posttransplant have been obtained,
      and clinicians working with this population remain concerned regarding the
      cognitive functions of these survivors. Research focused on these domains should
      attempt to better understand the prevalence of the problem using child self
      report and direct measurements of function, standardize measurement methods, and
      tools across trials, obtain longer term evaluations and begin to consider
      interventional trials.

PMID- 22155141
TI  - Successful remission rates and survival after lymphodepleting chemotherapy and
      donor lymphocyte infusion for relapsed hematologic malignancies postallogeneic
      hematopoietic cell transplantation.
AB  - Few therapeutic strategies exist for hematologic malignancies relapsing post
      allogeneic hematopoietic cell transplantation. We present outcomes on 35 patients
      with nonchronic myelogenous leukemia (CML) hematologic malignancies, the majority
      having acute myelogenous leukemia (AML) or myelodysplastic
      syndromes/myeloproliferative disorders (MDS/MPD) (n = 22) receiving
      lymphodepleting chemotherapy followed by donor lymphocyte infusion (DLI) at 2 T
      cell dose levels (0.5 and 1.0 * 10(8) CD3/kg). Forty-nine percent of patients
      achieved complete remission (CR), with a median duration of remission of 6 months
      (range: 2-71+). CR rates were similar between the 2 groups. The incidence of
      acute graft-versus-host disease (aGVHD) of any grade was 49%. We saw a higher
      incidence of grade II-IV aGVHD, with a rate of 66% using the higher-dose DLI
      (grade III, 33% and grade 4, 20%) versus only 25% (10% grade III-IV) with the
      lower-dose DLI (P = .06). Overall survival at 1 and 2 years was 30% (95%
      confidence interval [CI], 16%-45%) and 19% (95% CI, 8%-34%); however, for those
      achieving CR, 1- and 2-year survival was improved at 44% (95% CI, 20%-66%) and
      28% (95% CI, 8%-52%) (P = .03), respectively. These results demonstrate that DLI
      after lymphodepleting chemotherapy for relapsed hematologic malignancies results
      in frequent CRs. The lower DLI dose regimen improved the tolerability of this
      therapeutic approach, with modest rates of severe aGVHD.

PMID- 22155140
TI  - Soluble tumor necrosis factor receptor: enbrel (etanercept) for subacute
      pulmonary dysfunction following allogeneic stem cell transplantation.
AB  - Subacute lung disease, manifested as either obstructive (OLD) or restrictive
      (RLD) lung dysfunction, is a common complication following allogeneic stem cell
      transplantation. In each case, therapeutic options are limited, morbidity remains
      high, and long-term survival is poor. Between 2001 and 2008, 34 patients with
      noninfectious, obstructive (25) or RLD restrictive lung dysfunction (nine)
      received etanercept (Enbrel(r), Amgen Inc.) 0.4 mg/kg/dose, subcutaneously, twice
      weekly, for 4 (group A) or 12 weeks (group B). Corticosteroids (if present at
      study entry) were kept constant for the initial 4 weeks of therapy and then
      tapered as tolerated. Thirty-one of 34 (91%) subjects were evaluable for
      response, and 10 (32%) met primary response criteria. There was no difference in
      response based on the duration of treatment (29% group A versus 35% group B; P =
      .99), the presence of RLD or OLD (33% versus 32%; P = .73), or the severity of
      pulmonary disease at study onset. Estimated 5-year overall survival rates
      following therapy were 61% (95% confidence interval, 46%-80%) for all subjects
      and 90% (95% confidence level, 73%-100%) for the 10 who met the primary response
      criteria. Five-year survival estimates for subjects treated with RLD was 44%,
      compared with 67% for those treated for OLD (P = .19). Etanercept was well
      tolerated, with no bacteremia or viremia observed. Pathogens were noted on
      posttherapy bronchoalveolar lavage in two cases. These data support the
      development of expanded clinical trials to study etanercept as a therapeutic
      agent for subacute lung injury after allogeneic stem cell transplantation.

PMID- 22155142
TI  - Trichostatin A and sirtinol suppressed survivin expression through AMPK and
      p38MAPK in HT29 colon cancer cells.
AB  - BACKGROUND: Elevated levels of survivin and histone deacetylases (HDACs) are
      often found over-expressed in human cancers, including colorectal cancer, and
      have been implicated in tumorigenesis. HDAC inhibition induces growth arrest and
      cell death in various transformed cell; however, the mechanisms by which this
      reduces cell viability in colorectal cancer cells remain unexplained. METHODS: We
      explored the actions of two HDAC inhibitors, trichostatin A (TSA) and sirtinol,
      in HT29 colon cancer cells. RESULTS: TSA and sirtinol induced apoptosis and
      inhibited cell proliferation in HT29 cells. These results are associated with the
      modulation of survivin. Survivin promoter luciferase activity and Sp1, a
      transcription factor that contributes to survivin expression, were suppressed in
      cells exposed to TSA or sirtinol. TSA and sirtinol also activated p38 mitogen
      activated protein kinase (p38MAPK) and AMP-activated protein kinase (AMPK).
      Inhibitors of p38MAPK or AMPK signaling abrogated TSA and sirtinol's effects of
      decreasing cell viability. Survivin promoter luciferase activity in the presence
      of TSA or sirtinol was restored by AMPK dominant negative mutant or p38MAPK
      inhibitor. Furthermore, Sp1 binding to the survivin promoter region decreased
      while p63 binding to the promoter region increased after TSA or sirtinol
      exposure. CONCLUSIONS: We report a p38MAPK- and AMPK-mediated downregulation of
      survivin, and its functional correlation with decreased colon cancer cell
      viability in the presence of HDAC inhibitor. p63 and Sp1 may also contribute to
      TSA and sirtinol actions. GENERAL SIGNIFICANCE: This study delineates, in part,
      the underlying mechanisms of TSA and sirtinol in decreasing survivin expression
      and subsequent colon cancer cell viability.

PMID- 22155143
TI  - Large enhancement of skeletal muscle cell glucose uptake and suppression of
      hepatocyte glucose-6-phosphatase activity by weak uncouplers of oxidative
      phosphorylation.
AB  - BACKGROUND: Perturbation of energy homeostasis in skeletal muscle and liver
      resulting from a transient inhibition of mitochondrial energy transduction can
      produce effects of relevance for the control of hyperglycemia through activation
      of the AMP-activated protein kinase, as exemplified by the antidiabetic drug
      metformin. The present study focuses on uncoupling of oxidative phosphorylation
      rather than its inhibition as a trigger for such effects. METHODS: The reference
      weak uncoupler 2,4-dinitrophenol, fourteen naturally-occurring phenolic compounds
      identified as uncouplers in isolated rat liver mitochondria, and fourteen related
      compounds with little or no uncoupling activity were tested for enhancement of
      glucose uptake in differentiated C2C12 skeletal muscle cells following 18 h of
      treatment at 25-100 MUM. A subset of compounds were tested for suppression of
      glucose-6-phosphatase (G6Pase) activity in H4IIE hepatocytes following 16 h at
      12.5-25 MUM. Metformin (400 MUM) was used as a standard in both assays. RESULTS:
      Dinitrophenol and nine of eleven compounds that induced 50% or more uncoupling at
      100 MUM in isolated mitochondria enhanced basal glucose uptake by 53 to 269%; the
      effect of the 4'-hydroxychalcone butein was more than 6-fold that of metformin;
      negative control compounds increased uptake by no more than 25%. Dinitrophenol
      and four 4'-hydroxychalconoids also suppressed hepatocyte G6Pase as well as, or
      more effectively than metformin, whereas the unsubstituted parent compound
      chalcone, devoid of uncoupling activity, had no effect. CONCLUSIONS: Activities
      key to glycemic control can be induced by a wide range of weak uncouplers,
      including compounds free of difficult-to-metabolize groups typically associated
      with uncouplers. GENERAL SIGNIFICANCE: Uncoupling represents a valid and possibly
      more efficient alternative to inhibition for triggering cytoprotective effects of
      therapeutic relevance to insulin resistance in both muscle and liver.
      Identification of actives of natural origin and the insights into their structure
      activity relationship reported herein may lead to alternatives to metformin.

PMID- 22155144
TI  - The efficacy of intranasal live attenuated influenza vaccine in children 2
      through 17 years of age: a meta-analysis of 8 randomized controlled studies.
AB  - BACKGROUND: Nine randomized controlled clinical trials, including approximately
      26,000 children aged 6 months to 17 years, have evaluated the efficacy of live
      attenuated influenza vaccine (LAIV) against culture-confirmed influenza illness
      compared with placebo or trivalent inactivated influenza vaccine (TIV). The
      objective of the current analysis was to integrate available LAIV efficacy data
      in children aged 2-17 years, the group for whom LAIV is approved for use.
      METHODS: A meta-analysis was conducted using all available randomized controlled
      trials and a fixed-effects model. Cases caused by drifted influenza B were
      analyzed as originally classified and with all antigenic variants classified as
      dissimilar. RESULTS: Five placebo-controlled trials (4 were 2-season trials) and
      3 single-season TIV-controlled trials were analyzed. Compared with placebo, year
      1 efficacy of 2 doses of LAIV was 83% (95% CI: 78, 87) against antigenically
      similar strains; efficacy was 87% (95% CI: 78, 93), 86% (95% CI: 79, 91), and 76%
      (95% CI: 63, 84) for A/H1N1, A/H3N2, and B, respectively. Classifying B variants
      as dissimilar, efficacy against all similar strains was 87% (95% CI: 83, 91) and
      93% (95% CI: 83, 97) against similar B strains. Year 2 efficacy was 87% (95% CI:
      82, 91) against similar strains. Compared with TIV, LAIV recipients experienced
      44% (95% CI: 28, 56) and 48% (95% CI: 38, 57) fewer cases of influenza illness
      caused by similar strains and all strains, respectively. LAIV efficacy estimates
      for children from Europe, the United States, and Middle East were robust and were
      similar to or higher than those for the overall population. CONCLUSIONS: In
      children aged 2-17 years, LAIV demonstrated high efficacy after 2 doses in year 1
      and revaccination in year 2, and greater efficacy compared with TIV. This meta
      analysis provides precise estimates of LAIV efficacy among the approved pediatric
      age group.

PMID- 22155145
TI  - To TST or not to TST: is tuberculin skin testing necessary before BCG
      immunisation in children?
AB  - Bacille Calmette-Guerin (BCG) vaccine is one of the most commonly administered
      vaccines worldwide. In countries with high tuberculosis (TB) prevalence, it is
      generally given shortly after birth. In a number of low TB prevalence countries,
      BCG is used as a travel vaccine, typically given to children outside the neonatal
      period prior to visiting regions where TB is common. In this setting, it is
      recommended that latent TB infection (LTBI) resulting from prior exposure to
      Mycobacterium tuberculosis is excluded by a tuberculin skin test (TST) before BCG
      immunisation. This is to avoid the risk of an accelerated local reaction that is
      more common in individuals who have LTBI. In addition, BCG immunisation in
      individuals with LTBI is unnecessary, as it does not provide protection against
      progression to active TB disease. We review and discuss current international
      guidelines and recommendations on the need to screen children for LTBI prior to
      BCG immunisation. Guidelines vary significantly regarding age-related cut-offs
      and additional selection criteria. This variation primarily reflects the lack of
      evidence on which to base recommendations. We suggest an alternative strategy
      using a risk assessment questionnaire to identify children who should have a TST
      before BCG immunisation. This targeted approach will reduce the number of
      children unnecessarily screened, whilst allowing the identification of those with
      LTBI, who need further evaluation and treatment.

PMID- 22155146
TI  - Identification of a novel U2HR mutation c.14C>T in a Chinese patient with Marie
      Unna hereditary hypotrichosis.
AB  - Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of non
      syndromic hereditary alopecia. Recently, loss-of-function mutations of an
      inhibitory upstream open reading frame (ORF) in the human hairless gene (HR),
      named U2HR, have been identified in some patients with MUHH. We investigated a
      sporadic Chinese patient with MUHH and identified a novel mutation in U2HR,
      c.14C>T (p.T5M), which extends the mutation spectrum of U2HR mutations.

PMID- 22155147
TI  - Influence of erythrocyte oxygenation and intravascular ATP on resting and
      exercising skeletal muscle blood flow in humans with mitochondrial myopathy.
AB  - Oxygen (O2) extraction is impaired in exercising skeletal muscle of humans with
      mutations of mitochondrial DNA (mtDNA), but the muscle hemodynamic response to
      exercise has never been directly investigated. This study sought to examine the
      extent to which human skeletal muscle perfusion can increase without reductions
      in blood oxygenation and to determine whether erythrocyte O2 off-loading and
      related ATP vascular mechanisms are impaired in humans with mutations of mtDNA.
      Leg vascular hemodynamic, oxygenation and ATP were investigated in ten patients
      with mtDNA mutations and ten matched healthy control subjects: 1) at rest during
      normoxia, hypoxia, hyperoxia and intra-femoral artery ATP infusion, and 2) during
      passive and dynamic one-legged knee-extensor exercises. At rest, blood flow
      (LBF), femoral arterial and venous blood oxygenation and plasma ATP were similar
      in the two groups. During dynamic exercise, LBF and vascular conductance
      increased 9-10 fold in the patients despite erythrocyte oxygenation and leg O2
      extraction remained unchanged (p<0.01). In the patients, workload-adjusted LBF
      was 28% to 62% higher during submaximal- and maximal exercises and was associated
      with augmented plasma ATP. The appropriate hemodynamic adjustments during severe
      hypoxia and ATP infusion suggest that erythrocyte O2 off-loading and related ATP
      vascular mechanisms are intact in patients with mtDNA mutations. Furthermore,
      greater increase in plasma ATP and LBF at a given metabolic demand in the
      patients, in concert with unchanged oxyhemoglobin, suggest that erythrocyte O2
      off-loading is not obligatory for the exercise-induced increase in blood flow and
      intravascular ATP concentration.

PMID- 22155148
TI  - Speciation of trace elements in human serum by micro anion exchange
      chromatography coupled with inductively coupled plasma mass spectrometry.
AB  - Speciation analysis of essential trace elements in human serum provides important
      information on nutritional status and homeostatic mechanisms regulating transport
      processes, acute phase reactions, and protection against oxidative damage. Anion
      exchange high-performance liquid chromatography (HPLC) combined with inductively
      coupled plasma mass spectrometry (ICP-MS) has proved to be a useful tool in
      speciation. Here we describe a fast method that can be applied to carry out the
      speciation of Fe, Cu, Zn, and Se in as little as 1 microl [corrected] of serum.
      The method employs monolithic anion exchange micro columns installed on a tandem
      HPLC system coupled on-line with an ICP-MS detector. The chromatographic
      separation is similar to those reported previously but with considerable gain in
      terms of time and sample requirement. Reproducibility is acceptable for most
      species. Using our method, we were able to find species-specific differences
      between different commercially available trace element reference materials.
      Because the method chosen to collect blood might interfere with speciation, the
      proposed methodology was used to compare heparinized plasma,
      ethylenediaminetetraacetic acid (EDTA) plasma, and serum from adult healthy
      volunteers. As expected, EDTA strongly affects speciation analysis (especially
      for Fe and Zn), whereas changes due to the use of lithium-heparin (Li-He) as
      anticoagulant appear to be minimized.

PMID- 22155149
TI  - Low copy number DNA profiling from isolated sperm using the aureka(r)
      micromanipulation system.
AB  - A new cell isolation technique linked to the aureka(r) micromanipulation system
      (aureka(r)) was used to pick sperm from mixed samples containing sperm and
      epithelial cells. Both cell types were stained using the HY-LITERTM high
      resolution, fluorescent staining kit. To isolate a single sperm of interest under
      a fluorescent microscope, a specific microsphere picking technique was used. This
      sensitive and reliable cell identification and isolation technique enables low
      copy-number (LCN) DNA profiling, as few as 20 sperm are sufficient for obtaining
      a full short tandem repeat (STR) profile without any allelic drop out. The
      presented protocol covers the whole workflow, from sample staining and cell pick
      up to STR analysis.

PMID- 22155150
TI  - Autophagy enhanced phagocytosis of apoptotic cells by oridonin-treated human
      histocytic lymphoma U937 cells.
AB  - Macrophages rapidly engulf and remove apoptotic cells to limit the release of
      noxious cellular contents and to restrict autoimmune disease or inflammation.
      Recent developments reveal an important role in autophagy for clearance of
      apoptotic corpses. However, the relationship between autophagy and phagocytosis
      remains unclear. In this study we found that low doses of oridonin, an active
      diterpenoid, enhanced phagocytosis of apoptotic cells by human macrophage-like
      U937 cells, meanwhile it also induced autophagy in these U937 cells. Moreover,
      inhibition of extracellular signal-related kinase (ERK), nuclear factor-kappaB
      (NF-kappaB) and caspase-1 significantly suppressed oridonin-induced phagocytosis
      and autophagy. In addition, oridonin increased the protein levels of p-ERK, NF
      kappaB, caspase-1 and pro IL-1beta. Autophagic inhibitor 3-methyladenine (3-MA)
      decreased phagocytosis and the expression of ERK whereas increased the expression
      of NF-kappaB- and caspase-1-mediated IL-1beta release. Beclin-1 (known as
      autophagic regulator) loss also led to the similar results. Pretreatment with
      autophagic agonist rapamycin caused opposite results. Autophagy-associated
      proteins, Beclin-1, LC3 and Atg4B, involved in this phagocytosis process. These
      results demonstrated that autophagy enhanced oridonin-induced phagocytosis
      through feedback regulation of ERK, NF-kappaB- and caspase-1-mediated IL-1beta
      release.

PMID- 22155151
TI  - Vitamin D, the placenta and pregnancy.
AB  - Impaired vitamin D status is common to many populations around the world.
      However, data suggest that this is a particular problem for specific groups such
      as pregnant women. This has raised important questions concerning the
      physiological and clinical impact of low vitamin D levels during pregnancy, with
      implications for classical skeletal functions of vitamin D, as well as its
      diverse non-classical actions. The current review will discuss this with specific
      emphasis on the classical calciotropic effects of vitamin D as well as the less
      well established immunological functions of vitamin D that may influence
      pregnancy outcome. The review also describes the pathways that are required for
      metabolism and function of vitamin D, and the various clinical complications that
      have been linked to impaired vitamin D status during pregnancy.

PMID- 22155152
TI  - An antibiotic selection marker for schistosome transgenesis.
AB  - Drug selection is widely used in transgene studies of microbial pathogens,
      mammalian cell and plant cell lines. Drug selection of transgenic schistosomes
      would be desirable to provide a means to enrich for populations of transgenic
      worms. We adapted murine leukaemia retrovirus vectors - widely used in human gene
      therapy research - to transduce schistosomes, leading to integration of
      transgenes into the genome of the blood fluke. A dose-response kill curve and
      lethal G418 (geneticin) concentrations were established: 125-1,000MUg/ml G418
      were progressively more toxic for schistosomules of Schistosoma mansoni with
      toxicity increasing with antibiotic concentration and with duration of exposure.
      By day 6 of exposure to ?500MUg/ml, significantly fewer worms survived compared
      with non-exposed controls and by day 8, significantly fewer worms survived than
      controls at ?250MUg/ml G418. When schistosomules were transduced with murine
      leukaemia retrovirus encoding the neomycin resistance (neoR) transgene and
      cultured in media containing G418, the neoR transgene rescued transgenic
      schistosomules from the antibiotic; by day 4 in 1,000MUg/ml and by day 8 in
      500MUg/ml G418, significantly more transgenic worms survived the toxic effects of
      the antibiotic. More copies of neoR were detected per nanogram of genomic DNA
      from populations of transgenic schistosomes cultured in G418 than from transgenic
      schistosomes cultured without G418. This trend was G418 dose-dependent,
      demonstrating enrichment of transgenic worms from among the schistosomules
      exposed to virions. Furthermore, higher expression of neoR was detected in
      transgenic schistosomes cultured in the presence of G418 than in transgenic worms
      cultured without antibiotic. The availability of antibiotic selection can be
      expected to enhance progress with functional genomics research on the helminth
      parasites responsible for major neglected tropical diseases.

PMID- 22155154
TI  - Effects of decorin and biglycan on human airway smooth muscle cell adhesion.
AB  - Growth on a decorin matrix results in decreased human airway smooth muscle cell
      (HASMC) number, by decreasing proliferation and increasing apoptosis. We
      questioned whether these effects were related to abnormal extracellular matrix
      (ECM)-cell adhesion. HASMCs were seeded on decorin, biglycan, collagen type I or
      plastic. Actin organization and focal adhesion formation were assessed by
      staining for filamentous (F) and globular (G) actin, and vinculin, respectively.
      Gene expression for focal adhesion proteins, ECM molecules and HASMC receptors
      was measured. Protein levels for fibronectin, alpha(2), alpha(5), alpha(v) and
      beta(3) integrin subunits and, focal adhesion kinase (FAK) were assessed. F-actin
      filaments were prominent in cells seeded on collagen I and plastic, less apparent
      in cells cultured on biglycan and faint in cells on decorin. Vinculin clustering
      was decreased in cells seeded on decorin and biglycan, as was vinculin gene
      expression. Compared to cells on plastic, cells on decorin had an increase in
      fibronectin gene expression. Seeding on decorin caused an increase in alpha(2)
      integrin subunit and platelet-derived growth factor receptor A gene expression.
      There was also an increase in alpha(2) and alpha(v) integrin subunit protein.
      Finally, FAK protein levels in cells seeded on decorin or biglycan were decreased
      compared to cells seeded on plastic or collagen I. Cells grown on proteoglycan
      matrices demonstrate evidence of abnormalities during many of the key processes
      involved in normal cell adhesion. Upregulation of cell surface receptor proteins,
      such as alpha(2) integrin subunit, may represent a compensatory mechanism to
      overcome poor adhesion induced by growth on these matrices.

PMID- 22155153
TI  - Hyaluronan and versican in the control of human T-lymphocyte adhesion and
      migration.
AB  - The ability of lymphocytes to migrate freely through connective tissues is vital
      to efficient immune function. How the extracellular matrix (ECM) may affect T
      cell adhesion and migration is not well understood. We have examined the adhesion
      and migration of activated human T-lymphocytes on ECM made by fibroblast-like
      synoviocytes and lung fibroblasts. These cells were minimally interactive until
      treated with a viral mimetic, Poly I:C. This treatment promoted myofibroblast
      formation and engendered a higher-order structured ECM, rich in versican and
      hyaluronan, to which T-cells avidly adhered in a hyaluronidase-sensitive manner.
      This Poly I:C-induced matrix impeded T-cell spreading and migration on and
      through synoviocyte monolayers, while hyaluronidase treatment or adding versican
      antibody during matrix formation reversed the effect on T-cell migration.
      Hyaluronidase also reversed the spread myofibroblast morphology. These data
      suggest that the viscous hyaluronan- and versican-rich matrix binds and
      constrains T-lymphocytes. Using purified matrix components and solid state
      matrices of defined composition, we uncovered a role for versican in modulating
      hyaluronan-T-cell interactions. Versican prevented T-cell binding to soluble
      hyaluronan, as well as the amoeboid shape change on hyaluronan-coated dishes and
      T-cell penetration of collagen gels. Together, these data suggest that hyaluronan
      and versican play a role in T-cell trafficking and function in inflamed tissues.

PMID- 22155155
TI  - Transcript expression levels of full-length alpha-synuclein and its three
      alternatively spliced variants in Parkinson's disease brain regions and in a
      transgenic mouse model of alpha-synuclein overexpression.
AB  - Alternative splicing is a complex post-transcriptional process that can be
      regulated by cis-acting elements located within genomic non-coding regions.
      Recent studies have identified that polymorphic variations in non-coding regions
      of the alpha-synuclein gene (SNCA) locus are associated with an increased risk
      for developing Parkinson's disease (PD). The underlying mechanism(s) for this
      susceptibility may involve changes in alpha-synuclein mRNA expression and
      alternative splicing. As a first step towards understanding the biology of alpha
      synuclein splice variants in PD, we characterized the levels of the full-length
      SNCA-140 mRNA transcript and SNCA-126, -112, and -98 alternatively spliced
      variants in different neuronal regions from PD patients or transgenic mice
      overexpressing human alpha-synuclein (ASO). In human post-mortem tissue, alpha
      synuclein spliced transcripts were expressed in a region-specific manner in the
      cortex, substantia nigra, and cerebellum. We observed increased nigral SNCA-140
      and SNCA-126 transcript levels in PD patients when compared to neurologically
      unaffected cases. Human alpha-synuclein splicing changes were also found to occur
      in a region-specific manner in ASO mice. Here, SNCA-126, -112, and -98 transcript
      levels did not increase proportionally with SNCA-140 levels, or parallel the
      region-specific mouse transcript ratios seen in wild-type (WT) littermates. While
      most transcripts were elevated in ASO mice when compared to WT mice, the most
      prominent increase was found in the ventral midbrain of 15-month-old ASO mice.
      These results demonstrate region-specific human alpha-synuclein transcript level
      abnormalities in PD patients and in a transgenic mouse model of alpha
      synucleinopathy. This study is relevant to understanding the normal, adaptive, or
      pathological role(s) of alpha-synuclein splice variants.

PMID- 22155156
TI  - PTEN regulates retinal interneuron morphogenesis and synaptic layer formation.
AB  - The lipid phosphatase PTEN is a critical negative regulator of extracellular
      signal-induced PI3K activities, yet the roles of PTEN in the neural retina remain
      poorly understood. Here, we investigate the function of PTEN during retinal
      development. Deletion of Pten at the onset of neurogenesis in retinal progenitors
      results in the reduction of retinal ganglion cells and rod photoreceptors, but
      increased Muller glial genesis. In addition, PTEN deficiency leads to elevated
      phosphorylation of Akt, especially in the developing inner plexiform layer, where
      high levels of PTEN are normally expressed. In Pten mutant retinas, various
      subtypes of amacrine cells show severe dendritic overgrowth, causing specific
      expansion of the inner plexiform layer. However, the outer plexiform layer
      remains relatively undisturbed in the Pten deficient retina. Physiological
      analysis detects reduced rod function and augmented oscillatory potentials
      originating from amacrine cells in Pten mutants. Furthermore, deleting Pten or
      elevating Akt activity in individual amacrine cells is sufficient to disrupt
      dendritic arborization, indicating that Pten activity is required cell
      autonomously to control neuronal morphology. Moreover, inhibiting endogenous Akt
      activity attenuates inner plexiform layer formation in vitro. Together, these
      findings demonstrate that suppression of PI3K/Akt signaling by PTEN is crucial
      for proper neuronal differentiation and normal retinal network formation.

PMID- 22155158
TI  - How should veterinary surgeons adapt to achieve animal welfare?

PMID- 22155157
TI  - Enhanced charge-independent mitochondrial free Ca(2+) and attenuated ADP-induced
      NADH oxidation by isoflurane: Implications for cardioprotection.
AB  - Modulation of mitochondrial free Ca(2+) ([Ca(2+)](m)) is implicated as one of the
      possible upstream factors that initiates anesthetic-mediated cardioprotection
      against ischemia-reperfusion (IR) injury. To unravel possible mechanisms by which
      volatile anesthetics modulate [Ca(2+)](m) and mitochondrial bioenergetics, with
      implications for cardioprotection, experiments were conducted to
      spectrofluorometrically measure concentration-dependent effects of isoflurane
      (0.5, 1, 1.5, 2mM) on the magnitudes and time-courses of [Ca(2+)](m) and
      mitochondrial redox state (NADH), membrane potential (DeltaPsi(m)), respiration,
      and matrix volume. Isolated mitochondria from rat hearts were energized with 10mM
      Na(+)- or K(+)-pyruvate/malate (NaPM or KPM) or Na(+)-succinate (NaSuc) followed
      by additions of isoflurane, 0.5mM CaCl(2) (~200nM free Ca(2+) with 1mM EGTA
      buffer), and 250MUM ADP. Isoflurane stepwise: (a) increased [Ca(2+)](m) in state
      2 with NaPM, but not with KPM substrate, despite an isoflurane-induced slight
      fall in DeltaPsi(m) and a mild matrix expansion, and (b) decreased NADH
      oxidation, respiration, DeltaPsi(m), and matrix volume in state 3, while
      prolonging the duration of state 3 NADH oxidation, respiration, DeltaPsi(m), and
      matrix contraction with PM substrates. These findings suggest that isoflurane's
      effects are mediated in part at the mitochondrial level: (1) to enhance the net
      rate of state 2 Ca(2+) uptake by inhibiting the Na(+)/Ca(2+) exchanger (NCE),
      independent of changes in DeltaPsi(m) and matrix volume, and (2) to decrease the
      rates of state 3 electron transfer and ADP phosphorylation by inhibiting complex
      I. These direct effects of isoflurane to increase [Ca(2+)](m), while depressing
      NCE activity and oxidative phosphorylation, could underlie the mechanisms by
      which isoflurane provides cardioprotection against IR injury at the mitochondrial
      level.

PMID- 22155159
TI  - Weather factor impacts on commuting to work by bicycle.
AB  - OBJECTIVE: Quantify the impact of weather conditions on individual decisions to
      commute to work by bicycle among a diverse panel of adults who commute >=2 miles
      each way. METHOD: Working adults (n=163) in a northern U.S. state reported
      transportation mode for four seven-day periods in 2009-2010 that maximized
      seasonal weather variations. Personal characteristics, trip to work distances,
      and commuting mode data were linked to location- and time-specific weather data
      and daylight hours. Analyses focused on effect of weather conditions on reports
      of commuting by bicycle. RESULTS: Participants were diverse in age, gender and
      bicycle use, but were relatively well-educated; they traveled to work by bicycle
      on 34.5% of the logged commuting days. Modeling indicated that the likelihood of
      bicycle commuting increased in the absence of rain (odds ratio=1.91; 95%
      confidence interval 1.42, 2.57) and with higher temperatures (1.03; 1.02, 1.04),
      and decreased with snow (0.90; 0.84, 0.98) and wind (0.95; 0.92, 0.97).
      Independent effects also were found for bicycle commuting distance, gender, and
      age, but not for daylight hours. CONCLUSION: Precipitation, temperature, wind and
      snow conditions had significant and substantial independent effects on the odds
      of travel to work by bicycle among a diverse panel of adult bicycle commuters.

PMID- 22155160
TI  - Combined impact of five lifestyle factors and subsequent risk of cancer: the
      Japan Public Health Center Study.
AB  - OBJECTIVE: To evaluate whether 5 combined healthy lifestyle factors (not smoking,
      moderate drinking, eating minimum salt-preserved foods, being physically active,
      and having appropriate body mass index) are associated with reduced risk of
      cancer. METHODS: Participants were enrolled in the Japan Public Health Center
      Study and responded to the 5-year follow-up questionnaire covering lifestyle
      factors in 1995-1999 at ages 45-74 years. During follow up through December 31,
      2006, 3451 and 2125 cases of cancer were newly identified in men and women,
      respectively. For men and women, a factor-dependent risk reduction was observed
      for healthy lifestyles and cancer development. Compared to 0-1 healthy lifestyle
      factors, the adjusted RRs and 95% CIs for adherence to 2, 3, 4, and 5 healthy
      factors were 0.86 (0.78-0.95), 0.72 (0.65-0.80), 0.61 (0.54-0.69), and 0.57 (0.45
      0.72), respectively, for men (P for trend<0.0001) and 0.86 (0.53-1.40), 0.73
      (0.46-1.16), 0.68 (0.42-1.08), and 0.63 (0.39-1.01), respectively, for women (P
      for trend=0.0003). Risk was reduced 14% and 9% by each one healthy lifestyle for
      men and women, respectively. Risk reduction was more pronounced among elderly
      women. CONCLUSION: These combined lifestyle factors have a considerable impact on
      preventing cancer.

PMID- 22155161
TI  - Activation of hexosamine pathway impairs nitric oxide (NO)-dependent arteriolar
      dilations by increased protein O-GlcNAcylation.
AB  - We hypothesized that under high glucose conditions, activation of the hexosamine
      pathway leads to impaired nitric oxide (NO)-dependent arteriolar dilation.
      Skeletal muscle arterioles (diameter: ~160MUm) isolated from male Wistar rats
      were exposed to normal glucose (NG, 5.5mmol/L) or high glucose concentrations
      (HG, 30mmol/L, for 2h) and agonist-induced diameter changes were measured with
      videomicroscopy. Western blots were performed to identify the vascular levels of
      protein O-linked-N-acetyl-glucosamine (O-GlcNAc) and phosphorylated endothelial
      NO synthase (eNOS). In arterioles exposed to HG, dilations to histamine were
      abolished compared to those exposed to NG (max: -6+/-6% and 69+/-9%,
      respectively), while acetylcholine-induced responses were not affected.
      Inhibition of NO synthesis with N(G)-nitro-l-arginine methyl ester (L-NAME)
      reduced histamine-induced dilations in NG arterioles, but it had no effect on
      microvessels exposed to HG. Dilations to the NO donor, sodium nitroprusside and
      constrictions to norepinephrine and serotonin were similar in the two groups. In
      the presence of the inhibitor of hexosamine pathway, azaserine, histamine-induced
      dilations were significantly augmented in arterioles exposed to HG (max: 67+/
      2%). Moreover, exposure of vessels to glucosamine (5mmol/L, for 2h) resulted in
      reduced histamine-induced arteriolar dilations (max: 26+/-3%). The level of
      protein O-GlcNAcylation was increased, whereas the P-eNOS (Ser-1177) was
      decreased in HG exposed vessels. These findings indicate that a high
      concentration of glucose may lead to glucosamine formation, which impairs
      histamine-induced, NO-mediated arteriolar dilations. We propose that interfering
      with the hexosamine pathway may prevent microvascular complications in diabetes.

PMID- 22155162
TI  - Ethanol induces vascular relaxation via redox-sensitive and nitric oxide
      dependent pathways.
AB  - We investigated the role of reactive oxygen species (ROS) and nitric oxide (NO)
      in ethanol-induced relaxation. Vascular reactivity experiments showed that
      ethanol (0.03-200 mmol/L) induced relaxation in endothelium-intact and denuded
      rat aortic rings isolated from male Wistar rats. Pre-incubation of intact or
      denuded rings with l-NAME (non selective NOS inhibitor, 100 MUmol/L), 7
      nitroindazole (selective nNOS inhibitor, 100 MUmol/L), ODQ (selective inhibitor
      of guanylyl cyclase enzyme, 1 MUmol/L), glibenclamide (selective blocker of ATP
      sensitive K(+) channels, 3 MUmol/L) and 4-aminopyridine (selective blocker of
      voltage-dependent K(+) channels, 4-AP, 1 mmol/L) reduced ethanol-induced
      relaxation. Similarly, tiron (superoxide anion (O(2)(-)) scavenger, 1 mmol/L) and
      catalase (hydrogen peroxide (H(2)O(2)) scavenger, 300 U/mL) reduced ethanol
      induced relaxation to a similar extent in both endothelium-intact and denuded
      rings. Finally, prodifen (non-selective cytochrome P450 enzymes inhibitor, 10
      MUmol/L) and 4-methylpyrazole (selective alcohol dehydrogenase inhibitor, 10
      MUmol/L) reduced ethanol-induced relaxation. In cultured aortic vascular smooth
      muscle cells (VSMCs), ethanol stimulated generation of NO, which was
      significantly inhibited by l-NAME. In endothelial cells, flow cytometry studies
      showed that ethanol increased cytosolic Ca(2+) concentration ([Ca(2+)]c), O(2)(-)
      and cytosolic NO concentration ([NO]c). Tiron inhibited ethanol-induced increase
      in [Ca(2+)]c and [NO]c. The major new finding of this work is that ethanol
      induces relaxation via redox-sensitive and NO-cGMP-dependent pathways through
      direct effects on ROS production and NO signaling. These findings identify
      putative molecular mechanisms whereby ethanol, at pharmacological concentrations,
      influences vascular reactivity.

PMID- 22155163
TI  - Sulforaphane suppresses vascular adhesion molecule-1 expression in TNF-alpha
      stimulated mouse vascular smooth muscle cells: involvement of the MAPK, NF-kappaB
      and AP-1 signaling pathways.
AB  - Atherosclerosis is a long-term inflammatory disease of the arterial wall.
      Increased expression of the cell adhesion molecules such as intercellular
      adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) is
      associated with increased proliferation of vascular smooth muscle cells (VSMCs),
      leading to increased neointima or atherosclerotic lesion formation. Therefore,
      the functional inhibition of adhesion molecules could be a critical therapeutic
      target of inflammatory disease. In the present study, we investigate the effect
      of sulforaphane on the expression of VCAM-1 induced by TNF-alpha in cultured
      mouse vascular smooth muscle cell lines. Pretreatment of VSMCs for 2h with
      sulforaphane (1-5MUg/ml) dose-dependently inhibited TNF-alpha-induced adhesion of
      THP-1 monocytic cells and protein expression of VCAM-1. Sulforaphane also
      suppressed TNF-alpha-induced production of intracellular reactive oxygen species
      (ROS) and activation of p38, ERK and JNK. Furthermore, sulforaphane inhibited NK
      kappaB and AP-1 activation induced by TNF-alpha. Sulforaphane inhibited TNF-alpha
      induced IotakappaBeta kinase activation, subsequent degradation of
      IotakappaBetaalpha and nuclear translocation of p65 NF-kappaB and decreased c-Jun
      and c-Fos protein level. This study suggests that sulforaphane inhibits the
      adhesive capacity of VSMC and downregulates the TNF-alpha-mediated induction of
      VCAM-1 in VSMC by inhibiting the MAPK, NF-kappaB and AP-1 signaling pathways and
      intracellular ROS production. Thus, sulforaphane may have beneficial effects to
      suppress inflammation within the atherosclerotic lesion.

PMID- 22155164
TI  - Arachidonic acid inhibits Na+-K+-ATPase via cytochrome P-450, lipoxygenase and
      protein kinase C-dependent pathways in sheep pulmonary artery.
AB  - The purpose of the study was to examine whether arachidonic acid inhibits
      vascular Na(+)-K(+)-ATPase in pulmonary vasculature and if so, what are the
      mechanisms involved. Functional Na(+)-K(+)-ATPase activity was studied in terms
      of K(+)-induced relaxation in sheep pulmonary arterial rings contracted with K(+)
      free solution and 5-HT. Arachidonic acid (10-100 MUM) caused concentration
      dependent inhibition of KCl-induced relaxations and also increased basal arterial
      tone. Cytochrome P-450 inhibitor, 17-octadecynoic acid (17-ODYA) completely
      reversed the arachidonic acid (30 MUM)-induced inhibition of KCl relaxation.
      Further, in the presence of HET0016, a selective blocker of 20
      hydroxyeicosatetraenoic acid (20-HETE), arachidonic acid-induced inhibition of
      KCl relaxation was not evident. Accordingly, 20-HETE, a cytochrome P-450
      metabolite of arachidonic acid, also significantly attenuated KCl-induced
      relaxations. Norhydihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor,
      however, partially restored the relaxation to K(+), impaired in the presence of
      arachidonic acid (30 MUM). On the other hand, cyclooxygenase inhibitor
      indomethacin failed to reverse the inhibitory effect of arachidonic acid on KCl
      induced relaxation. Staurosporin, a protein kinase C inhibitor, completely
      reversed the inhibitory effect of arachidonic acid and 20-HETE on K(+)-induced
      relaxation. In conclusion, the results suggest that 20-HETE, a cytochrome P-450
      metabolite of arachidonic acid has a predominant role in the inhibition of
      functional Na(+)-K(+)-ATPase activity in the sheep pulmonary artery, while the
      lipooxygenase pathway has a secondary role. It is also evident that protein
      kinase C is involved in the inhibition of Na(+)-K(+)-ATPase by arachidonic
      acid/20-HETE in sheep pulmonary artery.

PMID- 22155165
TI  - Identification of the galactitol dehydrogenase, LadB, that is part of the oxido
      reductive D-galactose catabolic pathway in Aspergillus niger.
AB  - For the catabolism of D-galactose three different metabolic pathways have been
      described in filamentous fungi. Apart from the Leloir pathway and the oxidative
      pathway, there is an alternative oxido-reductive pathway. This oxido-reductive
      pathway has similarities to the metabolic pathway of L-arabinose, and in
      Trichoderma reesei (Hypocrea jecorina) and Aspergillus nidulans the same enzyme
      is employed for the oxidation of L-arabitol and galactitol. Here we show evidence
      that in Aspergillus niger L-arabitol dehydrogenase (LadA) is not involved in the
      D-galactose metabolism; instead another dehydrogenase encoding gene, ladB, is
      induced in response to D-galactose and galactitol and functions as a galactitol
      dehydrogenase. Deletion of ladB in A. niger results in growth arrest on
      galactitol and significantly slower growth on D-galactose supplemented with a
      small amount of D-xylose. D-galactose alone cannot be utilised by A. niger and
      the addition of D-xylose stimulates growth on D-galactose via transcriptional
      activation of the D-xylose-inducible reductase gene, xyrA. XyrA catalyses the
      first step of the D-galactose oxido-reductive pathway, the reduction to
      galactitol, which in turn seems to be an inducer of the downstream genes such as
      LadB. The deletion of xyrA results in reduced growth on D-galactose. The ladB
      gene was expressed in the heterologous host Saccharomyces cerevisiae and the
      tagged and purified enzyme characterised. LadB and LadA have similar in vitro
      activity with galactitol. It was confirmed that the reaction product of the LadB
      reaction from galactitol is L-xylo-3-hexulose as in the case of the T. reesei
      Lad1.

PMID- 22155166
TI  - Neuraxial anesthesia and timing of heparin administration in patients undergoing
      surgery for congenital heart disease using cardiopulmonary bypass.
AB  - OBJECTIVE: The goal of this review was to add to the existing literature
      documenting the safety of performing neuraxial techniques in patients who are
      subsequently fully heparinized, with particular emphasis on the timing of heparin
      administration. This will help improve risk estimation and possibly lead to a
      more widespread use of neuraxial anesthesia in patients undergoing cardiac
      surgery. DESIGN: Retrospective chart review. SETTING: Single tertiary-care
      university hospital. PARTICIPANTS: All patients undergoing surgery for congenital
      heart diseases during a 5-year period. INTERVENTIONS: The medical records of all
      patients undergoing surgery for congenital heart diseases during a 5-year period
      were reviewed for any complications related to the use of neuraxial anesthesia.
      Furthermore, the interval from neuraxial anesthesia to heparinization for
      cardiopulmonary bypass was examined. RESULTS: In total, 714 patients were
      identified who had neuraxial anesthesia administered before full heparinization
      for cardiopulmonary bypass. No cases of symptomatic spinal or epidural hematomas
      occurred. Further analysis showed that the interval from neuraxial anesthesia to
      full heparinization was <1 hour in 466 patients. CONCLUSIONS: No complications
      related to neuraxial anesthesia were found in a series of 714 patients undergoing
      surgery for congenital heart disease using cardiopulmonary bypass, including 466
      patients in whom the interval from neuraxial anesthesia to full heparinization
      was <1 hour.

PMID- 22155167
TI  - Intracardiac clots masked by extracorporeal membrane oxygenation venous cannula.

PMID- 22155168
TI  - Possible anaphylaxis due to recombinant factor VIIa administration during
      thoracic aortic surgery.

PMID- 22155169
TI  - Intraoperative detection of aortic dissection after off-pump coronary artery
      bypass grafting.

PMID- 22155170
TI  - Transesophageal echocardiographic examination in the diagnosis of bowel ischemia
      due to thoracic aorta thrombosis.

PMID- 22155171
TI  - High risk of benzo[alpha]pyrene-induced lung cancer in E160D FEN1 mutant mice.
AB  - Flap endonuclease 1 (FEN1), a member of the Rad2 nuclease family, possesses 5'
      flap endonuclease (FEN), 5' exonuclease (EXO), and gap-endonuclease (GEN)
      activities. The multiple, structure-specific nuclease activities of FEN1 allow it
      to process different intermediate DNA structures during DNA replication and
      repair. We previously identified a group of FEN1 mutations and single nucleotide
      polymorphisms that impair FEN1's EXO and GEN activities in human cancer patients.
      We also established a mouse model carrying the E160D FEN1 mutation, which mimics
      the mutations seen in humans. FEN1 mutant mice developed spontaneous lung cancer
      at high frequency at their late life stages. An important unanswered question is
      whether individuals carrying such FEN1 mutation are more susceptible to tobacco
      smoke and have an earlier onset of lung cancer. Here, we report our study on
      E160D mutant mice exposed to benzo[alpha]pyrene (B[alpha]P), a major DNA damaging
      compound found in tobacco smoke. We demonstrate that FEN1 employs its GEN
      activity to cleave DNA bubble substrates with BP-induced lesions, but the E160D
      FEN1 mutation abolishes such activity. As a consequence, Mouse cells carrying the
      E160D mutation display defects in the repair of B[alpha]P adducts and accumulate
      DNA double-stranded breaks and chromosomal aberrations upon treatments with
      B[alpha]P. Furthermore, more E160D mice than WT mice have an early onset of
      B[alpha]P-induced lung adenocarcinoma. All together, our current study suggests
      that individuals carrying the GEN-deficient FEN1 mutations have high risk to
      develop lung cancer upon exposure to B[alpha]P-containing agents such as tobacco
      smoke.

PMID- 22155172
TI  - Rifaximin-extended intestinal release induces remission in patients with
      moderately active Crohn's disease.
AB  - BACKGROUND & AIMS: Bacteria might be involved in the development and persistence
      of inflammation in patients with Crohn's disease (CD), and antibiotics could be
      used in therapy. We performed a clinical phase 2 trial to determine whether a
      gastroresistant formulation of rifaximin (extended intestinal release [EIR])
      induced remission in patients with moderately active CD. METHODS: We performed a
      multicenter, randomized, double-blind trial of the efficacy and safety of 400,
      800, and 1200 mg rifaximin-EIR, given twice daily to 402 patients with moderately
      active CD for 12 weeks. Data from patients given rifaximin-EIR were compared with
      those from individuals given placebo, and collected during a 12-week follow-up
      period. The primary end point was remission (Crohn's Disease Activity Index <150)
      at the end of the treatment period. RESULTS: At the end of the 12-week treatment
      period, 62% of patients who received the 800-mg dosage of rifaximin-EIR (61 of
      98) were in remission, compared with 43% of patients who received placebo (43 of
      101) (P = .005). A difference was maintained throughout the 12-week follow-up
      period (45% [40 of 89] vs 29% [28 of 98]; P = .02). Remission was achieved by 54%
      (56 of 104) and 47% (47 of 99) of the patients given the 400-mg and 1200-mg
      dosages of rifaximin-EIR, respectively; these rates did not differ from those of
      placebo. Patients given the 400-mg and 800-mg dosages of rifaximin-EIR had low
      rates of withdrawal from the study because of adverse events; rates were
      significantly higher among patients given the 1200-mg dosage (16% [16 of 99]).
      CONCLUSIONS: Administration of 800 mg rifaximin-EIR twice daily for 12 weeks
      induced remission with few adverse events in patients with moderately active CD.

PMID- 22155173
TI  - Glucocorticoid-induced tumor necrosis factor receptor family-related protein
      regulates CD4(+)T cell-mediated colitis in mice.
AB  - BACKGROUND & AIMS: The glucocorticoid-induced tumor necrosis factor receptor
      family-related protein (GITR; also called TNFRSF18 or CD357) regulates the T cell
      mediated immune response and is present on surfaces of regulatory T (Treg) cells
      and activated CD4(+) T cells. We investigated the roles of GITR in the
      development of colitis in mice. METHODS: Chronic enterocolitis was induced by the
      transfer of wild-type or GITR(-/-) CD4(+) T cells to GITR(-/-) * Rag(-/-) or Rag(
      /-) mice. We determined the severity of colitis by using the disease activity
      index; measured levels of inflammatory cytokines, T cells, and dendritic cells;
      and performed histologic analysis of colon samples. RESULTS: Transfer of
      nonfractionated CD4(+) cells from wild-type or GITR(-/-) donors induced colitis
      in GITR(-/-) * Rag(-/-) but not in Rag(-/-) mice. Among mice with transfer
      induced colitis, the percentage of Treg and T-helper (Th) 17 cells was reduced
      but that of Th1 cells increased. Treg cells failed to prevent colitis in GITR(-/
      ) * Rag(-/-) recipients; this was not the result of aberrant function of GITR(-/
      ) Treg or T effector cells but resulted from an imbalance between the numbers of
      tolerogenic CD103(+) and PDCA1(+) plasmacytoid dendritic cells in GITR(-/-) mice.
      This imbalance impaired Treg cell development and expanded the Th1 population in
      GITR(-/-) * Rag(-/-) mice following transfer of nonfractionated CD4(+) cells.
      CONCLUSIONS: GITR is not required on the surface of Treg and T effector cells to
      induce colitis in mice; interactions between GITR and its ligand are not required
      for induction of colitis. GITR instead appears to control dendritic cell and
      monocyte development; in its absence, mice develop aggravated chronic
      enterocolitis via an imbalance of colitogenic Th1 cells and Treg cells.

PMID- 22155175
TI  - Structural features and bioavailability of four flavonoids and their implications
      for lifespan-extending and antioxidant actions in C. elegans.
AB  - Various studies have demonstrated longevity effects of flavonoids, a major sub
      group of plant polyphenolic compounds, in Caenorhabditis elegans. To better
      understand their structure-activity relationship in vivo we have used a
      comparative approach by exposing C. elegans to the structurally related
      flavonoids myricetin, quercetin, kaempferol and naringenin, and assessed their
      impact on lifespan and on putative modes of action. The bioavailability of the
      tested flavonoids was demonstrated by high-performance liquid chromatography with
      diode-array detection (HPLC/DAD) and a 2-aminoethyl diphenyl borate-based in vivo
      approach. While all flavonols increased lifespan in wild-type, only myricetin
      elongated the mev-1(kn1) lifespan, suggesting that the flavonols antioxidant
      action alone is not sufficient for longevity. Structural prerequisites of high
      antioxidant action in vitro were also essential to reduce the reactive oxygen
      species (ROS) load in vivo in C. elegans and were tested in isolated mouse muscle
      mitochondria. Since the insulin/IGF-like signaling (IIS) cascade is a key
      regulator of lifespan, all compounds were tested for the ability to cause nuclear
      translocation of the FOXO transcription factor DAF-16 and changes in target gene
      expression. An increased DAF-16 translocation and sod-3 promoter activity were
      observed with all flavonoids but was independent of their ROS scavenging
      capability and their effects on lifespan.

PMID- 22155177
TI  - Increased white matter integrity in the corpus callosum in subjects with high
      genetic loading for schizophrenia.
AB  - OBJECTIVE: White matter abnormalities in the corpus callosum (CC) of
      schizophrenia have been reported to predate the illness onset. This study aimed
      to investigate the effect of genetic predisposition on the white matter integrity
      of the CC, in subjects at genetically high risk for schizophrenia (GHR) and
      schizophrenia patients. METHOD: Fractional anisotropy (FA) of the mid-sagittal CC
      in 22 young GHR, 15 schizophrenia, and 26 control subjects were examined. GHR
      subjects were defined as non-prodromal individuals who had more than two
      relatives with schizophrenia within third-degree relatives, one of whom must be a
      first-degree relative. RESULTS: ANCOVA with age and gender as covariates revealed
      overall difference of FA in the genu and splenium among the three groups. Post
      hoc analysis found significantly increased FA in the genu of GHR subjects
      compared to controls (corrected p<0.01), whereas schizophrenia patients showed
      significantly decreased FA in the splenium. CONCLUSION: The white matter change
      of the CC in young GHR subjects was the opposite of that in schizophrenia. To
      consider previous reports on FA decrease in the CC in schizophrenia and the
      impaired frontal functioning in GHR group, the increased FA may be an indicator
      of compensatory alteration in white matter integrity in young GHR people.

PMID- 22155176
TI  - Systems genetics of the nuclear factor-kappaB signal transduction network. I.
      Detection of several quantitative trait loci potentially relevant to aging.
AB  - A theory of aging holds that senescence is caused by a dysregulated nuclear
      factor kappa B (NF-kappaB) signal transduction network (STN). We adopted a
      systems genetics approach in our study of the NF-kappaB STN. Ingenuity Pathways
      Analysis (IPA) was used to identify gene/gene product interactions between NF
      kappaB and the genes in our transcriptional profiling array. Principal components
      factor analysis (PCFA) was performed on a sub-network of 19 genes, including two
      initiators of the toll-like receptor (TLR) pathway, myeloid differentiation
      primary response gene (88) (MyD88) and TIR (Toll/interleukin-1 receptor)-domain
      containing adapter-inducing interferon-beta (TRIF). TLR pathways are either MyD88
      dependent or TRIF-dependent. Therefore, we also performed PCFA on a subset
      excluding the MyD88 transcript, and on another subset excluding two TRIF
      transcripts. Using linkage analysis we found that each set gave rise to at least
      one factor with a logarithm of the odds (LOD) score greater than 3, two on
      chromosome 15 at 15q12 and 15q22.2, and another two on chromosome 17 at 17p13.3
      and 17q25.3. We also found several suggestive signals (2<LOD score<3) at 1q32.1,
      1q41, 2q34, 3q23, and 7p15.3. We are currently examining potential associations
      with single nucleotide polymorphisms within the 1-LOD intervals of our linkage
      signals.

PMID- 22155178
TI  - Structural basis of transcription by bacterial and eukaryotic RNA polymerases.
AB  - DNA-dependent RNA polymerase (RNAP) is responsible for cellular gene
      transcription. Although crystallographic studies on prokaryotic and eukaryotic
      RNAPs have elucidated the basic RNAP architectures, the structural details of
      many essential events during transcription initiation, elongation, and
      termination are still largely unknown. Recent crystallographic studies on a
      bacterial RNAP and yeast RNAP II have revealed different RNAP structural states
      from that of the normal transcribing complex, as well as the basis of
      transcription factor functions, advancing our understanding of transcription.
      These studies have highlighted unexpected similarities in many fundamental
      aspects of transcription mechanisms between the bacterial and eukaryotic
      transcription machineries. Remarkable differences also exist between the
      bacterial and eukaryotic transcription systems, suggesting directions for future
      studies.

PMID- 22155180
TI  - The two faces of Janus: functional interactions and protein aggregation.
AB  - Protein aggregation constitutes a constant threat for the living cell as is
      demonstrated by the several pathologies in which the mechanisms to prevent it
      fail. It is therefore a question of increasing importance to understand in detail
      the defence strategies. Here we discuss how molecular interactions can represent
      a general strategy to prevent aggregation. This view generalizes the more
      specific paradigm that suggests a competition between folding and aggregation,
      and allows to include both intrinsically unfolded proteins and proteins that
      aggregate also under native conditions. We analyze the factors that influence the
      balance between the two competing pathways and suggest new perspectives to
      increase our understanding of misfolding pathologies.

PMID- 22155179
TI  - Structural analyses clarify the complex control of mistranslation by tRNA
      synthetases.
AB  - Proteins are precisely assembled with amino acids by matching the anticodons of
      charged transfer RNAs to nucleotide triplets in mRNA sequences. Accurate
      translation depends on the specific coupling of cognate amino acids and tRNAs - a
      step carried out by aminoacyl-tRNA synthetases (aaRSs) and that generates the
      genetic code. Owing to their intrinsic similarity, aaRSs developed highly
      differentiated structures to discriminate between amino acids at the active site
      for aminoacylation. Because this discrimination is not sufficient to prevent
      toxic mistranslation, aaRSs developed separate structures to further refine
      recognition by proofreading. From comprehensive structural studies on aaRSs, many
      of the molecular details have been elucidated for the recognition of cognate
      amino acids and for the misactivation and editing of noncognate amino acids, Here
      we review recent advances in the structural description of the binding,
      activation and editing of amino acids, which collectively reveal many aspects of
      the fine-tuned systems that resulted in a robust and universal genetic code.

PMID- 22155181
TI  - The role of the frontal eye fields in the oculomotor inhibition of reflexive
      saccades: evidence from lesion patients.
AB  - The current study investigated the role of the frontal eye fields (FEF) in the
      suppression of an unwanted eye movement ('oculomotor inhibition'). Oculomotor
      inhibition has generally been investigated using the antisaccade task, in which
      an eye movement to a task-relevant onset must be inhibited. Various lines of
      research have suggested that successful inhibition in the antisaccade task relies
      heavily on the FEF. Here, we tested whether the FEF are also involved in the
      oculomotor inhibition of reflexive saccades. To this end, we used the oculomotor
      capture task in which the to-be-inhibited element is task-irrelevant. Performance
      of four patients with lesions to the FEF was measured on both the antisaccade and
      oculomotor capture task. In both tasks, the majority of the patients made more
      erroneous eye movements to contralesional elements than to ipsilesional elements.
      One patient showed no deficits in the antisaccade task, which could be explained
      by the developmental origin of his lesion. While we confirm the role of the FEF
      in the inhibition of task-relevant elements, the current study also reveals that
      the FEF play a crucial role in the oculomotor inhibition of task-irrelevant
      elements.

PMID- 22155182
TI  - Amitriptyline modulates calcium currents and intracellular calcium concentration
      in mouse trigeminal ganglion neurons.
AB  - Migraine is increasingly recognized as a channelopathy, and abnormalities of
      voltage-activated ionic channels could represent the molecular basis for the
      altered neuronal functioning. The high-voltage-activated (HVA) Ca(2+) channels in
      the trigeminovascular system play a role in the pathophysiology of migraine. In
      the present study, effects of amitriptyline (AMT), a commonly used migraine
      prophylactic drug, on the HVA calcium currents (I(Ca)) were examined in mouse
      trigeminal ganglion neurons using whole-cell patch clamp technique. AMT produced
      concentration- and use-dependent inhibition of HVA I(Ca). Bath application of GO
      6983 (a selective protein kinase C inhibitor) or H89 (a protein kinase A
      inhibitor) did not reduce the AMT-induced inhibition of HVA I(Ca). A similar
      inhibition was observed when calcium imaging was used to directly monitor the
      effects of AMT on KCl-induced increments of intracellular Ca(2+) concentration
      ([Ca(2+)](i)). By blocking HVA Ca(2+) channels and Ca(2+) entry into cells, AMT
      could prevent the release of neurotransmitters and help restore the neuronal
      threshold for excitation. Our findings suggest interesting therapeutic mechanisms
      for AMT in migraine prevention.

PMID- 22155183
TI  - Higher predicted vitamin D status is associated with reduced risk of Crohn's
      disease.
AB  - BACKGROUND & AIMS: Vitamin D influences innate immunity, which is believed to be
      involved in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC).
      However, data examining vitamin D status in relation to risk of CD and UC are
      lacking. METHODS: We conducted a prospective cohort study of 72,719 women (age,
      40-73 y) enrolled in the Nurses' Health Study. In 1986, women completed an
      assessment of diet and lifestyle, from which a 25-hydroxy vitamin D [25(OH)D]
      prediction score was developed and validated against directly measured levels of
      plasma 25(OH)D. Through 2008, we confirmed reported diagnoses of incident CD or
      UC through medical record review. We used Cox proportional hazards modeling to
      examine the hazard ratio (HR) for incident CD or UC after adjusting for potential
      confounders. RESULTS: During 1,492,811 person-years of follow-up evaluation, we
      documented 122 incident cases of CD and 123 cases of UC. The median predicted
      25(OH)D level was 22.3 ng/mL in the lowest and 32.2 ng/mL in the highest
      quartiles. Compared with the lowest quartile, the multivariate-adjusted HR
      associated with the highest quartile of vitamin D was 0.54 (95% confidence
      interval [CI], 0.30-.99) for CD (P(trend) = .02) and 0.65 (95% CI, 0.34-1.25) for
      UC (P(trend) = .17). Compared with women with a predicted 25(OH)D level less than
      20 ng/mL, the multivariate-adjusted HR was 0.38 (95% CI, 0.15-0.97) for CD and
      0.57 (95% CI, 0.19-1.70) for UC for women with a predicted 25(OH)D level greater
      than 30 ng/mL. There was a significant inverse association between dietary and
      supplemental vitamin D and UC, and a nonsignificant reduction in CD risk.
      CONCLUSIONS: Higher predicted plasma levels of 25(OH)D significantly reduce the
      risk for incident CD and nonsignificantly reduce the risk for UC in women.

PMID- 22155184
TI  - beta-catenin inhibits promyelocytic leukemia protein tumor suppressor function in
      colorectal cancer cells.
AB  - BACKGROUND & AIMS: Loss of promyelocytic leukemia protein (PML) nuclear body (NB)
      formation has been reported in colorectal and other solid tumors. However,
      genetic alteration of PML is rarely observed in these tumors; the exact
      mechanisms that mediate loss of PML function are not known. METHODS: We
      previously used a comprehensive shotgun mass spectrometry approach to identify
      PML as 1 of 70 proteins that coimmunoprecipitate with anti-T-cell factor 4 in DLD
      1 and HCT116 colorectal cancer cell lines; we investigated the effects of altered
      beta-catenin expression on PML function in these cells. RESULTS: beta-catenin
      specifically interacted with the product of PML transcript variant IV (PML-IV)
      through the armadillo repeat domain of beta-catenin. Overexpression of beta
      catenin in colorectal cancer cells disrupted the subcellular compartmentalization
      of PML-IV, whereas knockdown of beta-catenin restored formation of PML-NB.
      Modification of PML by the small ubiquitin-related modifier (SUMO) is required
      for proper assembly of PML-NB. beta-catenin inhibited Ran-binding protein 2
      mediated SUMOylation of PML-IV. CONCLUSIONS: beta-catenin interacts with PML
      isoform IV and disrupts PML-IV function and PML-NB formation by inhibiting Ran
      binding protein 2-mediated SUMO modification of PML-IV. These findings indicate
      the involvement of a posttranslational mechanism in disruption of PML-NB
      organization in cancer cells and provide more information about the oncogenic
      functions of beta-catenin.

PMID- 22155185
TI  - Recalcitrant pruritic urticarial papules and plaques of pregnancy with a
      prolonged course after delivery.

PMID- 22155186
TI  - DNA topoisomerase IIalpha inhibitory and anti-HIV-1 flavones from leaves and
      twigs of Gardenia carinata.
AB  - Four new flavones, 5,2'-dihydroxy-7,3',4',5'-tetramethoxyflavone (1), 5,2',5'
      trihydroxy-7,3',4'-trimethoxyflavone (2), 5,7,2',5'-tetrahydroxy-6,3',4'
      trimethoxyflavone (3) and 5,2',5'-trihydroxy-6,7,3',4'-tetramethoxyflavone (4),
      along with the known 5,3'-dihydroxy-6,7,4',5'-tetramethoxyflavone (5), 5,7,3',5'
      tetrahydroxy-6,4'-dimethoxyflavone (6), syringaldehyde, vanillic acid and
      scopoletin were isolated from the leaves and twigs of Gardenia carinata
      (Rubiaceae). Their structures were determined by spectroscopic methods. Flavone 2
      exhibited cytotoxic activity against P-388 and MCF-7 cell lines, while 3, 5 and 6
      were active only in P-388 cell line. All active compounds were found to inhibit
      DNA topoisomerase IIalpha activity, which may be responsible for the observed
      cytotoxicity. Flavones 1-3, 5 and 6 also exhibited anti-HIV-1 activity in the
      anti-syncytium assay using (?Tat/rev)MC99 virus and 1A2 cell line system; 2 was
      most potent. Only flavones 1 and 6 showed considerably activity against HIV-1
      reverse transcriptase.

PMID- 22155187
TI  - A natural theaflavins preparation inhibits HIV-1 infection by targeting the entry
      step: potential applications for preventing HIV-1 infection.
AB  - Theaflavins are the major components of tea polyphenols in brewed black tea. We
      previously reported that theaflavin derivatives, such as TF3, inhibited HIV-1
      entry by targeting gp41. However, it is difficult to purify the individual
      theaflavins and the purified compounds are highly unstable. To develop
      theaflavins as affordable anti-HIV-1 microbide for preventing HIV sexual
      transmission, we intended to use an economic natural preparation containing 90%
      of theaflavins (TFmix). Its antiviral activity against HIV-1 strains was
      evaluated in vitro using p24 production and luciferase assays. The mechanism by
      which TFmix inhibits HIV-1 infection was investigated using time-of-addition,
      cell-cell fusion and biophysical assays. The data suggested TFmix exhibited
      potent anti-HIV-1 activity on lab-adapted and primary HIV-1 strains with IC(50)
      less than 1.20 MUM. It also effectively inhibited infection by T-20 resistant HIV
      1 strains. The mechanism studies suggest that TFmix mainly inhibit the HIV-1
      entry by targeting gp41 since it is effective in inhibiting gp41 six-helix bundle
      (6-HB) formation and HIV-1 envelope protein-mediated cell-cell fusion. TFmix
      could also inhibit HIV-1 reverse transcriptase (RT) activity, but the IC(50) is
      about 8-fold higher than that for inhibiting gp41 6-HB formation, suggesting RT
      is not a major target for TFmix. In conclusion, TFmix is an economic natural
      product preparation containing high content of theaflavins with potent anti-HIV-1
      activity by targeting the viral entry step through the disruption of gp41 6-HB
      core structure. It has a potential to be developed as a safe and affordable
      topical microbicide for preventing sexual transmission of HIV.

PMID- 22155188
TI  - Potent antiviral flavone glycosides from Ficus benjamina leaves.
AB  - Crude ethanol extracts from Ficus benjamina leaves strongly inhibit Herpes
      Simplex Virus 1 and 2 (HSV-1/2) as well as Varicella Zoster Virus (VZV) cell
      infection in vitro. Bioassay-guided fractionation of the crude extract
      demonstrated that the most efficient inhibition of HSV-1 and HSV-2 was obtained
      with the flavonoid fraction. The present study was aimed to further isolate,
      purify and identify substances with potent antiviral activity from the flavonoid
      fraction of F. benjamina extracts. Flavonoids were collected from the leaf
      ethanol extracts through repeated purification procedure and HPLC analysis. The
      antiviral activity of each substance was then evaluated in cell culture. Three
      known flavone glycosides, (1) quercetin 3-O-rutinoside, (2) kaempferol 3-O
      rutinoside and (3) kaempferol 3-O-robinobioside, showing highest antiviral
      efficiency were selected and their structure was determined by spectroscopic
      analyses including NMR and mass spectrometry (MS). These three flavones were
      highly effective against HSV-1 reaching a selectivity index (SI) of 266, 100 and
      666 for compound 1, 2 and 3, respectively, while the SI of their aglycons,
      quercetin and kaempferol amounted only in 7.1 and 3.2, respectively. Kaempferol 3
      O-robinobioside showed similar SI to that of acyclovir (ACV), the standard anti
      HSV drug. Although highly effective against HSV-1 and HSV-2, these flavone
      glycosides did not show any significant activity against VZV.

PMID- 22155189
TI  - Four new neolignans from the leaves of Tripterygium wilfordii.
AB  - Four new neolignans, wilfordiols A-D (1-4), together with five known compounds (5
      9), were isolated from an aqueous extract of the dried leaves of Tripterygium
      wilfordii. Their structures were determined by spectroscopic methods, including
      1D and 2D NMR, HRESIMS, and CD experiments. The anti-inflammation activities of
      compounds 1-9 were evaluated by the inhibitory effect on NO production, in vitro.

PMID- 22155191
TI  - Modeling chondrocyte patterns by elliptical cluster processes.
AB  - Superficial zone chondrocytes (CHs) of human joints are spatially organized in
      distinct horizontal patterns. Among other factors, the type of spatial CH
      organization within a given articular surface depends on whether the cartilage
      has been derived from an intact joint or the joint is affected by osteoarthritis
      (OA). Furthermore, specific variations of the type of spatial organization are
      associated with particular states of OA. This association may prove relevant for
      early disease recognition based on a quantitative structural characterization of
      CH patterns. Therefore, we present a point process model describing the distinct
      morphology of CH patterns within the articular surface of intact human cartilage.
      This reference model for intact CH organization can be seen as a first step
      towards a model-based statistical diagnostic tool. Model parameters are fitted to
      fluorescence microscopy data by a novel statistical methodology utilizing tools
      from cluster and principal component analysis. This way, the complex morphology
      of surface CH patters is represented by a relatively small number of model
      parameters. We validate the point process model by comparing biologically
      relevant structural characteristics between the fitted model and data derived
      from photomicrographs of the human articular surface using techniques from
      spatial statistics.

PMID- 22155190
TI  - Isolation, electron microscopy and 3D reconstruction of invertebrate muscle
      myofilaments.
AB  - Understanding the molecular mechanism of muscle contraction and its regulation
      has been greatly influenced and aided by studies of myofilament structure in
      invertebrate muscles. Invertebrates are easily obtained and cover a broad
      spectrum of species and functional specializations. The thick (myosin-containing)
      filaments from some invertebrates are especially stable and simple in structure
      and thus much more amenable to structural analysis than those of vertebrates.
      Comparative studies of invertebrate filaments by electron microscopy and image
      processing have provided important generalizations of muscle molecular structure
      and function. This article reviews methods for preparing thick and thin filaments
      from invertebrate muscle, for imaging filaments by electron microscopy, and for
      determining their three dimensional structure by image processing. It also
      highlights some of the key insights into filament function that have come from
      these studies.

PMID- 22155192
TI  - The genetic association of DUSP6 with bipolar disorder and its effect on ERK
      activity.
AB  - The dual-specificity phosphatase 6 (DUSP6) gene resides at chromosome location
      12q22-23, which is one of the candidate loci for susceptibility to bipolar
      disorder and which encodes a phosphatase selective for extracellular signal
      regulated kinase (ERK). Previously, we reported a positive association between
      the functional Leu114Val polymorphism (rs2279574) in DUSP6 and bipolar disorder.
      Given that the association between DUSP6 and the reported down-regulation of
      DUSP6 transcript in bipolar postmortem brains were sex-dimorphic, showing
      significance in women but not men, we performed two independent analyses in
      homogenous samples of male and female Korean patients with bipolar disorder or
      schizophrenia using samples enlarged from our previous report. Among the examined
      DUSP6 SNPs, five (rs769700, rs704076, rs770087, rs808820, and rs2279574) showed
      positive allelic associations, with the frequency of minor alleles (C, T, G, G,
      and G) in each SNP significantly increased in women with BD. Consequently, the "C
      T-G-G-G" haplotype was significantly over-represented (P=0.016; OR=3.242),
      whereas the "T-G-T-A-T" haplotype was significantly under-represented (P=0.014;
      OR=0.697). We found no significant associations with DUSP6 SNPs in men with
      bipolar disorder or schizophrenia. We also investigated the functions of the
      functional SNPs' positive associations and found that Leu114Val (rs2279574; T/G)
      and Ser144Ala (rs770087; T/G) mutations in DUSP6 proteins reduced lithium-induced
      ERK1/2 phosphorylation in vitro, implicating the dominant active functions. Thus,
      DUSP6 may not only play important roles in the pathogenesis of bipolar disorder,
      particularly in women, but also affect the therapeutic response to lithium
      through modulating lithium's effects on intracellular signaling.

PMID- 22155193
TI  - Optimization of a whole blood intracellular cytokine assay for measuring innate
      cell responses to mycobacteria.
AB  - Innate cells are essential for host defense against invading pathogens, and the
      induction and direction of adaptive immune responses to infection. We developed
      and optimized a flow cytometric assay that allows measurement of intracellular
      cytokine expression by monocytes, dendritic cells (DC) and granulocytes, as well
      as cellular uptake of green-fluorescent protein (GFP)-expressing mycobacteria, in
      very small volumes of peripheral blood. We show that innate cell stimulation
      resulted in increased granularity of monocytes and mDC and decreased granulocyte
      granularity that precluded flow cytometric discernment of granulocytes from
      monocytes and myeloid DC by forward and side scatter gating. Anti-CD66a/c/e
      antibody staining allowed reliable identification and exclusion of granulocytes
      for subsequent delineation of monocytes and myeloid DC. Intracellular cytokine
      expression by granulocytes, monocytes and mDC was remarkably sensitive to the
      dose of mycobacterial inoculum. Moreover, activation of monocytes and mDC with
      live BCG reduced expression levels of CD14 and CD11c, respectively, necessitating
      optimization of staining conditions to reliably measure these lineage markers.
      Finally, we characterized expression of IL-12/23p40, TNF-alpha, IL-6, and IL-10,
      by GFP(+) and GFP(-) monocytes and mDC from 25 healthy adults. This assay may be
      applied to the study of innate cell responses to any GFP-expressing pathogen, and
      can be performed on blood volumes as low as 200 MUL per condition, making the
      assay particularly suitable for pediatric studies.

PMID- 22155194
TI  - Arg 901 in the AE1 C-terminal tail is involved in conformational change but not
      in substrate binding.
AB  - In our previous paper, we demonstrated that Arg 901 in the C-terminal tail of
      human AE1 (band 3, anion exchanger 1) had a functional role in conformational
      change during anion exchange. To further examine how Arg 901 is involved in
      conformational change, we expressed various Arg 901 mutants and alanine mutants
      of the C-terminal tail (from Leu 886 to Val 911) on the plasma membrane of
      Saccharomyces cerevisiae and evaluated the kinetic parameters of sulfate ion
      transport. As a result, Vmax decreased as the hydrophobicities of the 901st and
      peripheral hydrophilic residues increased, indicating that the hydrophobicity of
      the C-terminal residue is involved in the conformational change. We also found
      the alkali and protease resistance of the C-terminal region after Arg 901
      modification with hydroxyphenylglyoxal (HPG) or phenylglyoxal (PG), a hydrophobic
      reagent. These results suggested that the increased hydrophobicity of the C
      terminal region around Arg 901 leads to inefficient conformational change by the
      newly produced hydrophobic interaction.

PMID- 22155195
TI  - Analysis of fMRI time series with mutual information.
AB  - Neuroimaging plays a fundamental role in the study of human cognitive
      neuroscience. Functional magnetic resonance imaging (fMRI), based on the Blood
      Oxygenation Level Dependent signal, is currently considered as a standard
      technique for a system level understanding of the human brain. The problem of
      identifying regionally specific effects in neuroimaging data is usually solved by
      applying Statistical Parametric Mapping (SPM). Here, a mutual information (MI)
      criterion is used to identify regionally specific effects produced by a task. In
      particular, two MI estimators are presented for its use in fMRI data. The first
      one uses a Parzen probability density estimation, and the second one is based on
      a K Nearest Neighbours (KNN) estimation. Additionally, a statistical measure has
      been introduced to automatically detect the voxels which are relevant to the fMRI
      task. Experiments demonstrate the advantages of MI estimators over SPM maps;
      firstly, providing more significant differences between relevant and irrelevant
      voxels; secondly, presenting more focalized activation; and, thirdly, detecting
      small areas related to the task. These findings, and the improved performance of
      KNN MI estimator in multisubject and multistimuli studies, make the proposed
      methods a good alternative to SPM.

PMID- 22155196
TI  - The X chromosome and the sex ratio of autoimmunity.
AB  - The number of human conditions that are currently considered to be autoimmune
      diseases (AID) has been steadily growing over the past decades and it is now
      estimated that over 10 million people are affected in the United States. One of
      the major shared features among AID is the predominance in the female sex which
      in some cases changes with the age at disease diagnosis. Numerous hypotheses have
      been formulated based on intuitive scientific backgrounds to justify this sex
      imbalance, i.e. sex hormones and reproductive factors, fetal microchimerism,
      other sex-related environmental factors, a skewing of the X-chromosome
      inactivation patterns, and major defects in sex chromosomes. Nevertheless, none
      of these hypotheses has thus far gathered enough convincing evidence and in most
      cases data are conflicting, as well illustrated by the reports on fetal
      microchimerism in systemic sclerosis or primary biliary cirrhosis. The present
      article will critically discuss the main hypotheses (loss of mosaicism,
      reactivation, and haploinsufficiency) that have been proposed based on findings
      in female patients with specific AID along with two additional mechanisms (X
      chromosome vulnerability and X-linked polyamine genes) that have been observed in
      AID models. Further, recent data have significantly shifted the paradigm of X
      chromosome inactivation by demonstrating that a large number of genes can
      variably escape silencing on one or both chromosomes. As a result we may
      hypothesize that more than one mechanism may contribute to the female
      susceptibility to tolerance breakdown while the possibility that unknown factors
      may indeed protect men from AID should not be overlooked.

PMID- 22155197
TI  - Pregnancy and vasculitis: a systematic review of the literature.
AB  - Primary systemic vasculitis are uncommon diseases that may affect young women in
      their childbearing age. To date, patients affected with primary systemic
      vasculitis are often diagnosed and treated earlier than in the past, due to
      improvement in diagnostic skills and a larger availability of effective drugs.
      The progressive achievement of a longer life expectancy and a better quality of
      life have progressively led to an increased number of pregnancies observed during
      the course of such diseases. Here, we review 567 pregnancies among patients with
      primary systemic vasculitis, in order to define the relationship between
      pregnancy and these conditions and to suggest guidelines for their management.
      However, data on pregnancy outcomes are limited and knowledge about their
      gestational risk is mostly provided by single case reports or at best by
      retrospective studies which may result in intrinsic observational bias;
      unfortunately, long term prospective studies are still lacking. Analysis of the
      data highlighted a reciprocal influence between disease course and gestational
      outcome, although no definite effects can be outlined. Indeed, either improvement
      or worsening of the different vasculitis can occur, probably due to diverse
      genetic, clinical and immunological background of the patients. Since disease
      course may vary over time, careful management of systemic vasculitis during
      gestation is required. Furthermore, organ failure or damage must be carefully
      considered, since it can lead to adverse obstetrical and fetal outcomes.

PMID- 22155198
TI  - Estrogen metabolism and autoimmunity.
AB  - Epidemiological and experimental immunological evidence suggest that estrogens
      enhance the humoral immune response, and at the same time, seem to play important
      roles in pathophysiology of autoimmune rheumatic diseases. Estrogens in human
      subjects are generally considered as enhancers of cell proliferation (anti
      apoptotic), however, rather than through their serum levels (that may exert
      opposite dose-related effects), they play important roles through their
      peripheral metabolites especially in autoimmune rheumatic diseases. Several
      investigations strongly support an accelerated aromatase-mediated peripheral
      metabolic conversion of upstream androgen precursors to estrogen metabolites in
      peripheral tissues affected by immune/inflammatory reactions, both, in male and
      female patients. In RA synovial tissue, biological effects of these metabolites
      as a consequence of altered peripheral sex hormone synthesis (intracrine, e.g.,
      at the level of macrophages and fibroblasts) mainly results in stimulation of
      cell proliferation and cytokine production (i.e. TNF). It was shown that RA
      synovial cells mainly produce the cell proproliferative 16alpha-hydroxyestrone
      which, in addition to 16alpha-hydroxy-17beta-estradiol, is the downstream
      estrogen metabolite that interferes with monocyte proliferation. Therefore, a
      preponderance of 16alpha-hydroxylated estrogens is an unfavorable sign, at least,
      in synovial inflammation and possibly related synovial tissue hyperplasia.
      Interestingly, urinary concentration and total urinary loss of 2-hydroxyestrogens
      was found 10 times higher in healthy subjects compared to RA or SLE patients
      irrespective of prior prednisolone treatment or sex. The intracrine synthesis of
      active estrogen metabolites at the level of cells involved in the immune response
      (e.g. macrophages and fibroblasts) represents a common pathway that characterizes
      a similar final immune reactivity in both male and female patients.

PMID- 22155199
TI  - Pregnancy issues in scleroderma.
AB  - Systemic sclerosis is a systemic, inflammatory, autoimmune disease affecting the
      skin and viscera, manifesting pathologically with microvascular lesions,
      perivascular infiltration by mononuclear cells and increased deposition of
      extracellular collagen. The rarity of the disease as well as its propensity to
      appear in the early 1940s, explain the low frequency of concurrent scleroderma
      and pregnancy. However, the marked female excess, as well as the trend for
      increasing maternal age due to social change and assisted reproductive
      technologies, renders heightened significance to issues of fertility, pregnancy
      course and pregnancy outcomes. In the past, scleroderma patients were thought to
      be at high risk for poor fetal and maternal outcome, but more current
      retrospective studies show that despite an increased frequency of prematurity and
      small for gestational age infants, overall maternal and neonatal survival is
      good. Hence, at present, with close monitoring and appropriate therapy most
      scleroderma patients can sustain a successful pregnancy. Therapy with
      hydroxychloroquine and low dose steroids as well as judicious use of intravenous
      immunoglobulins is permitted. Renal crisis remains the most dreaded complication
      of a scleroderma pregnancy and necessitates prompt institution of ACE inhibitor
      therapy despite its potential teratogenicity. In order minimize the risk for
      renal crisis, pregnancies should be avoided in rapidly progressive diffuse
      disease as such patients are at a greater risk for developing serious
      cardiopulmonary and renal problems early in the disease. This review shall focus
      on the bi-directional effects of scleroderma on fertility and pregnancy as well
      as on the management of pregnancy and delivery in the scleroderma patient.

PMID- 22155200
TI  - Immunology and the menstrual cycle.
AB  - Sex and gender differences in disease prevalence, pathogenesis and modulation
      have been frequently reported. The menstrual cycle represents the opportunity to
      study the physiological effect of hormonal fluctuations in vivo on the immune
      function and chronic disease modulation. Reports on the effect of the cycle on
      immune cell numbers and activity fluctuations are scarce, but recent publications
      demonstrate an increasing interest in the subject. The menstrual cycle might
      affect immune cell numbers and modulate their activity throughout the 4-week
      cycle, as demonstrated in the case of regulatory T cells. The implications of
      these fluctuations are particularly relevant in the field of chronic diseases
      affecting women of reproductive age. In fact, baseline inflammation and immune
      cell activation in association with other mechanisms, such as regulation of
      receptor expression, modulation of muscular contraction and behavioral aspects
      might explain the menstrual-associated fluctuations described in chronic and
      acute diseases. In the following review the current knowledge about the
      modulatory effects of the menstrual cycle on both immune cells and systemic
      diseases, such as autoimmune diseases, asthma, diabetes, cardiac arrhythmia and
      schizophrenia, is reported. Most of these diseases display worsening of symptoms
      premenstrually or during menses due to physiologic effects on the target tissue
      mediated by progesterone and estrogen fluctuations and, thus, display
      paradigmatic changes potentially relevant to numerous other conditions.

PMID- 22155201
TI  - The influence of sex and gender on the immune response.
AB  - The immune system and its orchestrated response are affected by a multitude of
      endogenous and exogenous factors, modulators and challenges. One of the most
      frequent differences described in the immune response is its vigor and activity
      in females compared to males, leading to the consequent increase in autoimmune
      conditions seen in the female population as well as differences in the immune
      response to pathogens and viruses. The following review summarizes our present
      knowledge on sex differences in the immune response, detailing the hormonal and
      genetic effects that have been proposed as explanatory mechanisms. Sexual
      hormones, mostly estrogen but also progesterone and testosterone, affect immune
      cells quantitatively and qualitatively. Relevant research has focused on the
      impact of hormones on cytokine production by the different effector cells, as
      well as impact on immunoglobulin production by B lymphocytes and activity of
      granulocytes and NK cells. The biological aspects are complemented by research
      data on the possible modulatory role of the X chromosome. In addition to
      biological differences, the frequently neglected role of gender as an
      immunomodulator is introduced and explored. Gender affects all areas of human
      life and consequently affects the different steps of an immune response. Exposure
      to various types of antigens, access to health promotion programs and health
      care, as well as prioritization of health needs and household resource allocation
      all affect the different response of females and males to immunologic challenges.

PMID- 22155202
TI  - Sociological differences between women and men: implications for autoimmunity.
AB  - There are an enormous number of incorrect stereotypes that characterize the
      differences between women and men. Indeed, nearly all of these stereotypes are
      based on cultural inaccuracies and faulty data without consideration of biology
      and the distinct sociological differences between genders. Sociological
      differences are those that relate to the development, structure, interaction and
      behavior of organized groups of human beings, or societies, and their values and
      beliefs. Gender is a social construct referring "to the culturally and
      historically based differences in the roles, attitudes and behaviors of men and
      women" ([1], p.1) as shaped by norms and stereotypes. Sex, on the other hand,
      serves to classify living things according to their reproductive organs and
      functions assigned by chromosomal complement (according to the US Institute of
      Medicine) and the physical and biological characteristics arising from these
      organs and functions. The two terms are generally viewed as dichotomous; however,
      they are closely intertwined in as yet hardly understood ways, and it is
      frequently difficult to distinguish between them since gendered life experiences
      can have profound effects on body structure and function [2]. In this review, we
      will examine to what extent gender roles and stereotypes shape the daily lives of
      women in their roles as students, employees, wives, and mothers and their health.
      These data have implications for the etiology of autoimmunity and also for
      differences in the natural history of disease.

PMID- 22155203
TI  - Prolactin and autoimmunity.
AB  - Sex hormones, especially estrogen and prolactin (PRL), have an important role in
      modulating the immune response. PRL is secreted from the pituitary gland as well
      as other organs and cells particularly lymphocytes. PRL has an immune stimulatory
      effect and promotes autoimmunity. PRL interferes specifically with B cell
      tolerance induction, enhances proliferative response to antigens and mitogens and
      increases the production of immune globulins, cytokines and autoantibodies.
      Hyperprolactinemia (HPRL) in women present with clinical manifestations of
      galactorrhea, primary or secondary amenorrhea, delayed menarche or a change in
      the menses either in the amount or in the regularity. Furthermore in the last 2
      decades multi-organ and organ specific autoimmune diseases like systemic lupus
      erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS),
      Hashimoto's thyroiditis (HT), multiple sclerosis (MS), psoriasis, hepatitis C
      patients, Behcet's disease, peripartum cardiomyopathy (PPCM) and active celiac
      disease were discussed to be associated with HPRL. There is data showing
      correlation between PRL level and diseases activity in few diseases. Genetic
      factors may have a role in humans as in animal models. The PRL isoforms based on
      the differences in the amino acid sequence and size of the cytoplasmic domain
      have an important effect on the bioactivity on prolactin receptors (PRL-Rs).

PMID- 22155204
TI  - Human CD19(+)CD25(high) B regulatory cells suppress proliferation of CD4(+) T
      cells and enhance Foxp3 and CTLA-4 expression in T-regulatory cells.
AB  - Studies in both animal models and humans have shown a subset of B cells behaving
      as immuno-regulatory cells, being a source of inhibitory cytokines such as IL-10
      and TGF-beta. Our aims were to establish the presence of human B regulatory
      (Breg) cells and to assess their ability to suppress proliferation of CD4(+) T
      cells and to mediate T regulatory (Treg) cells' properties. For this purpose,
      human Breg, CD4(+) T and Treg cells were purified using magnetic microbeads. CFSE
      labeled CD4(+) T cells were stimulated and cultured alone or with Breg cells.
      Their proliferative response was determined 72 hours later based on the CFSE
      staining. In parallel, Treg cells were cultured alone or with Breg cells in
      different conditions for 24 hours, and then stained and analyzed for Foxp3 and
      CTLA-4 expression. We found that, the co-culture of Breg cells (defined as
      CD25(high) CD27(high) CD86(high) CD1d(high) IL-10(high) TGF-beta(high)) with
      autologous stimulated CD4(+) T cells decreased significantly (in a dose-dependent
      way) the proliferative capacity of CD4(+) T cells. Furthermore, Foxp3 and CTLA-4
      expression in Treg cells were enhanced by non-stimulated and further by ODN-CD40L
      stimulated Breg cells. The regulatory function of Breg cells on Treg cells was
      mainly dependent on a direct contact between Breg and Treg cells, but was also
      TGF-beta but not IL-10 dependent. In conclusion, human Breg cells decrease the
      proliferation of CD4(+) T cells and also enhance the expression of Foxp3 and CTLA
      4 in Treg cells by cell-to-cell contact.

PMID- 22155205
TI  - Polyvalent mechanical bacterial lysate for the prevention of recurrent
      respiratory infections: a meta-analysis.
AB  - BACKGROUND: Respiratory tract infections are common and remain a major source of
      morbidity, mortality and economic cost worldwide, despite advances in modern
      medicine. One treatment approach is to non-specifically increase the immune
      response or augment innate defense mechanisms through the use of bacterial
      lysates. Polyvalent Mechanical Bacterial Lysate (PMBL) is a bacterial lysate made
      from a wide range of pathogenic bacteria, including all of the most commonly
      occurring pathogens of the upper and lower respiratory tract obtained by
      mechanical lysis. AIM: To test the available evidence that PMBL is able to
      prevent respiratory tract infections. METHODS: A number of studies investigating
      randomized comparisons of PMBL (active) with placebo or no treatment (control)
      were selected for analysis. The primary outcome measure was the prevention of
      exacerbations or acute respiratory tract infection. The results were expressed as
      relative risk (RR) and the number of patients needed to treat for one to benefit
      (NNTB). RESULTS: Data from 2557 patients from 15 randomized clinical trials
      (RCTs) was investigated. PMBL induced a significant reduction of infections vs
      placebo (RR -0.513; 95% CI; -0.722 - -0.303; p = 0.00). The NNTB was 1.15. The RR
      was always in favor of PMBL (in recurrent respiratory infections other than COPD,
      chronic bronchitis and tuberculosis, RR -0.502; 95% CI -0.824 - -0.181; in
      children RR -2.204; 95% CI -3.260 - -1.147; in COPD or chronic bronchitis, RR 
      0.404; 95% CI -0.864-0.057; in tuberculosis, RR -0.502; 95% CI -0.890 - -0.114).
      CONCLUSIONS: The results of the present meta-analysis suggest that PBML is
      effective in both in children and in adults in preventing respiratory tract
      infections. Our current meta-analysis shows that there is a trend with PBML
      toward clinically significant results in patients with COPD but it did not quite
      achieve statistical significance due to the small number of COPD studies.

PMID- 22155206
TI  - Structure-activity relationships for allosteric NMDA receptor inhibitors based on
      2-naphthoic acid.
AB  - Over-activation of N-methyl-d-aspartate (NMDA) receptors is critically involved
      in many neurological conditions, thus there has been considerable interest in
      developing NMDA receptor antagonists. We have recently identified a series of
      naphthoic and phenanthroic acid compounds that allosterically modulate NMDA
      receptors through a novel mechanism of action. In the present study, we have
      determined the structure-activity relationships of 18 naphthoic acid derivatives
      for the ability to inhibit the four GluN1/GluN2(A-D) NMDA receptor subtypes. 2
      Naphthoic acid has low activity at GluN2A-containing receptors and yet lower
      activity at other NMDA receptors. 3-Amino addition, and especially 3-hydroxy
      addition, to 2-naphthoic acid increased inhibitory activity at GluN1/GluN2C and
      GluN1/GluN2D receptors. Further halogen and phenyl substitutions to 2-hydroxy-3
      naphthoic acid leads to several relatively potent inhibitors, the most potent of
      which is UBP618 (1-bromo-2-hydroxy-6-phenylnaphthalene-3-carboxylic acid) with an
      IC(50) ~ 2 MUM at each of the NMDA receptor subtypes. While UBP618 is non
      selective, elimination of the hydroxyl group in UBP618, as in UBP628 and UBP608,
      leads to an increase in GluN1/GluN2A selectivity. Of the compounds evaluated,
      specifically those with a 6-phenyl substitution were less able to fully inhibit
      GluN1/GluN2A, GluN1/GluN2B and GluN1/GluN2C responses (maximal % inhibition of 60
      90%). Such antagonists may potentially have reduced adverse effects by not
      excessively blocking NMDA receptor signaling. Together, these studies reveal
      discrete structure-activity relationships for the allosteric antagonism of NMDA
      receptors that may facilitate the development of NMDA receptor modulator agents
      for a variety of neuropsychiatric and neurological conditions.

PMID- 22155207
TI  - Bimodal effects of fluoxetine on cerebral nitrergic neurogenic vasodilation in
      porcine large cerebral arteries.
AB  - Fluoxetine-induced relaxation of the smooth muscle of small cerebral arteries is
      thought beneficial in treating mental disorders. The present study was designed
      to examine effect of fluoxetine on neurogenic nitrergic vasodilation in large
      cerebral arteries, using in vitro tissue myography, techniques of
      electrophysiology, calcium imaging and biochemistry. In isolated porcine
      endothelium-denuded basilar arteries in the presence of U-46619-induced active
      muscle tone, fluoxetine in low concentration (<0.03 MUM) significantly enhanced
      nicotine- and choline-induced relaxations. The vasorelaxation, however, was
      blocked by higher concentration of fluoxetine (>0.3 MUM) with maximum inhibition
      at 3 MUM. At this concentration, fluoxetine did not affect the basal tone or
      vasorelaxations induced by transmural nerve stimulation, sodium nitroprusside, or
      isoproterenol. Furthermore, fluoxetine exclusively blocked nicotine-induced
      inward currents and calcium influx in cultured neurons of rat superior cervical
      ganglion and Xenopus oocytes expressing human alpha7-, alpha3beta2-, or
      alpha4beta2-nicotinic acetylcholine receptors (nAChRs). In addition, fluoxetine
      at 0.03 MUM and 3 MUM significantly enhanced and blocked, respectively, nicotine
      induced norepinephrine (NE) release from cerebral perivascular sympathetic
      nerves. These results indicate that fluoxetine via axo-axonal interaction
      mechanism exhibits bimodal effects on nAChR-mediated neurogenic nitrergic
      dilation of basilar arteries. Fluoxetine in high concentrations decreases while
      in low concentrations it increases neurogenic vasodilation. These results from in
      vitro experimentation suggest that optimal concentrations of fluoxetine which
      increase or minimally affect neurogenic vasodilation indicative of regional
      cerebral blood flow may be important consideration in treating mental disorders.

PMID- 22155208
TI  - The noradrenaline transporter as site of action for the anti-Parkinson drug
      amantadine.
AB  - Amantadine is an established antiparkinsonian drug with a still unclear molecular
      site of action. In vivo studies on rodents, in vitro studies on tissue of rodents
      as well as binding studies on post mortem human tissue implicate monoamine
      transporters and NMDA receptors. In order to re-examine its action at human
      variants of these proteins on intact cells we established cells stably expressing
      the human NR1/2A NMDA-receptor, noradrenaline transporter (NAT) or dopamine
      transporter (DAT) and tested the activity of amantadine in patch-clamp, uptake,
      release, and cytotoxicity experiments. Amantadine was less potent in blockade of
      NMDA-induced inward currents than in blockade of noradrenaline uptake and in
      induction of inward currents in NAT expressing cells. It was 30 times more potent
      in blocking uptake in NAT- than in DAT cells. Amantadine induced NAT-mediated
      release at concentrations of 10-100 MUM in superfusion experiments and blocked
      NAT-mediated cytotoxicity of the parkinsonism inducing neurotoxin 1-methyl-4
      phenyl-pyridinium (MPP(+)) at concentrations of 30-300 MUM, whereas 300-1000 MUM
      amantadine was necessary to block NMDA-receptor mediated cytotoxicity. Similar to
      amphetamine, amantadine was inactive at alpha(2A)-adrenergic receptors and
      induced reverse noradrenaline transport by NAT albeit with smaller effect size.
      Thus, amantadine acted as "amphetamine-like releaser" with selectivity for the
      noradrenergic system. These findings and differences with memantine, which had
      been reported as less efficient antiparkinsonian drug than amantadine but in our
      hands was significantly more potent at the NMDA-receptor, suggest contributions
      from a noradrenergic mechanism in the antiparkinsonian action of amantadine.

PMID- 22155209
TI  - Assessing tungsten transport in the vadose zone: from dissolution studies to soil
      columns.
AB  - This study investigates the dissolution, sorption, leachability, and plant uptake
      of tungsten and alloying metals from canister round munitions in the presence of
      model, well characterized soils. The source of tungsten was canister round
      munitions, composed mainly of tungsten (95%) with iron and nickel making up the
      remaining fraction. Three soils were chosen for the lysimeter studies while four
      model soils were selected for the adsorption studies. Lysimeter soils were
      representatives of the typical range of soils across the continental USA; muck
      peat, clay-loamy and sandy-quartzose soil. Adsorption equilibrium data on the
      four model soils were modeled with Langmuir and linear isotherms and the model
      parameters were obtained. The adsorption affinity of soils for tungsten follows
      the order: Pahokee peat>kaolinite>montmorillonite>illite. A canister round
      munition dissolution study was also performed. After 24 d, the measured dissolved
      concentrations were: 61.97, 3.56, 15.83 mg L(-1) for tungsten, iron and nickel,
      respectively. Lysimeter transport studies show muck peat and sandy quartzose
      soils having higher tungsten concentration, up to 150 mg kg(-1) in the upper
      layers of the lysimeters and a sharp decline with depth suggesting strong
      retardation processes along the soil profile. The concentrations of tungsten,
      iron and nickel in soil lysimeter effluents were very low in terms of posing any
      environmental concern; although no regulatory limits have been established for
      tungsten in natural waters. The substantial uptake of tungsten and nickel by
      ryegrass after 120 d of exposure to soils containing canister round munition
      suggests the possibility of tungsten and nickel entering the food chain.

PMID- 22155210
TI  - Red antenna states of Photosystem I trimers from Arthrospira platensis revealed
      by single-molecule spectroscopy.
AB  - Single-molecule fluorescence spectroscopy at 1.4K was used to investigate the
      spectral properties of red (long-wavelength) chlorophylls in trimeric Photosystem
      I (PSI) complexes from the cyanobacterium Arthrospira platensis. Three distinct
      red antenna states could be identified in the fluorescence spectra of single PSI
      trimers from A. platensis in the presence of oxidized P700. Two of them are
      responsible for broad emission bands centered at 726 and 760nm. These bands are
      similar to those found in bulk fluorescence spectra measured at cryogenic
      temperatures. The broad fluorescence bands at ?726 and ?760nm belong to
      individual emitters that are broadened by strong electron-phonon coupling giving
      rise to a large Stokes-shift of about 20nm and rapid spectral diffusion. An
      almost perpendicular orientation of the transition dipole moments of F726 and
      F760 has to be assumed because direct excitation energy transfer does not occur
      between F726 and F760. For the first time a third red state assigned to the pool
      absorbing around 708nm could be detected by its zero-phonon lines. The center of
      the zero-phonon line distribution is found at ?714nm. The spectral properties of
      the three red antenna states show a high similarity to the red antenna states
      found in trimeric PSI of Thermosynechoccocus elongatus. Based on these findings a
      similar organization of the red antenna states in PSI of these two cyanobacteria
      is discussed.

PMID- 22155211
TI  - Connexins in wound healing; perspectives in diabetic patients.
AB  - Skin lesions are common events and we have evolved to rapidly heal them in order
      to maintain homeostasis and prevent infection and sepsis. Most acute wounds heal
      without issue, but as we get older our bodies become compromised by poor blood
      circulation and conditions such as diabetes, leading to slower healing. This can
      result in stalled or hard-to-heal chronic wounds. Currently about 2% of the
      Western population develop a chronic wound and this figure will rise as the
      population ages and diabetes becomes more prevalent [1]. Patient morbidity and
      quality of life are profoundly altered by chronic wounds [2]. Unfortunately a
      significant proportion of these chronic wounds fail to respond to conventional
      treatment and can result in amputation of the lower limb. Life quality and
      expectancy following amputation is severely reduced. These hard to heal wounds
      also represent a growing economic burden on Western society with published
      estimates of costs to healthcare services in the region of $25B annually [3].
      There exists a growing need for specific and effective therapeutic agents to
      improve healing in these wounds. In recent years the gap junction protein Cx43
      has been shown to play a pivotal role early on in the acute wound healing process
      at a number of different levels [4-7]. Conversely, abnormal expression of Cx43 in
      wound edge keratinocytes was shown to underlie the poor rate of healing in
      diabetic rats, and targeting its expression with an antisense gel restored normal
      healing rates [8]. The presence of Cx43 in the wound edge keratinocytes of human
      chronic wounds has also been reported [9]. Abnormal Cx43 biology may underlie the
      poor healing of human chronic wounds and be amenable therapeutic intervention
      [7]. This article is part of a Special Issue entitled: The Communicating
      junctions, composition, structure and characteristics.

PMID- 22155212
TI  - Channel-independent influence of connexin 43 on cell migration.
AB  - In this review we focus on the role of connexins, especially of Cx43, as
      modulators of migration - a fundamental process in embryogenesis and in
      physiologic functions of the adult organism. This impact of connexins is partly
      mediated by their function as intercellular channels but an increasing number of
      studies support the view that at least part of the effects are truly independent
      of the channel function. The channel-independent function comprises extrinsic
      guidance of migrating cells due to connexin mediated cell adhesion as well as
      intracellular processes. Cx43 has been shown to exert effects on migration by
      interfering with receptor signalling, cytoskeletal remodelling and tubulin
      dynamics. These effects are mainly dependent on the presence of the carboxyl tail
      of Cx43. The molecular basis of this channel-independent connexin function is
      still not yet fully understood but early results open an exciting view towards
      new functions of connexins in the cell. This article is part of a Special Issue
      entitled: The Communicating junctions, composition, structure and
      characteristics.

PMID- 22155213
TI  - The positive halochromism of phenolate dyes in hydroxylic solutions of
      tetraalkylammonium cations.
AB  - By contrast with the negative halochromic behaviour shown by phenolate betaines
      in the presence of alkaline and alkaline-earth cations, the addition of
      tetraalkylammonium salts to hydroxylic solutions of these dyes generate
      bathochromic shifts of their charge-transfer band. This positive halochromic
      behaviour by organic cations was examined systematically and its origin
      rationalized by nonspecific changes of the medium permittivity, and by specific
      dye-cation interactions in solution.

PMID- 22155214
TI  - Immobilization of tyrosinase on chitosan-clay composite beads.
AB  - Tyrosinase was immobilized on glutaraldehyde crosslinked chitosan-clay composite
      beads and used for phenol removal. Immobilization yield, loading efficiency and
      activity of tyrosinase immobilized beads were found as 67%, 25% and 1400 U/g
      beads respectively. Optimum pH of the free and immobilized enzyme was found as pH
      7.0. Optimum temperature of the free and immobilized enzyme was determined as 25
      30  degrees C and 25  degrees C respectively. The kinetic parameters of free and
      immobilized tyrosinase were calculated using l-catechol as a substrate and K(m)
      value for free and immobilized tyrosinase were found as 0.93 mM and 1.7 mM
      respectively. After seven times of repeated tests, each over 150 min, the
      efficiency of phenol removal using same immobilized tyrosinase beads were
      decreased to 43%.

PMID- 22155215
TI  - Practical synthesis and characterization of mannose-modified chitosan.
AB  - A new and practical laboratory approach to synthesize mannose modified chitosan
      (Man-chitosan) was developed via reductive amination reaction. Chitosan and
      mannose were used as raw materials. The reaction condition was mild and
      controllable. The overall yield was 47-52%. Each reaction products and Man
      chitosan were characterized by (1)H NMR, ESI-MS, FT-IR and TGA spectrum. FT-IR
      and (1)H NMR results showed that mannose conjugated to chitosan via an alkane
      chain bridge (CH(2)CH(2)). The degree of substitution was calculated by element
      analysis. TGA results indicated that mannose grafted to chitosan slightly
      decreased the thermal stability of chitosan in some extent. MTT assay indicated
      that Man-chitosan was low cytotoxicity against HepG-2 and SMMC-7721 cells.

PMID- 22155216
TI  - Peptide screening to knockdown Bcl-2's anti-apoptotic activity: implications in
      cancer treatment.
AB  - Bcl-2 (B cell lymphoma-2) is an anti-apoptotic member of Bcl-2 family and its
      overexpression causes development of several types of cancer. The BH3 domain of
      pro-apoptotic and BH3-only proteins is capable of binding to Bcl-2 protein to
      induce apoptosis. This binding is the basis for the development of novel
      anticancer drug which would likely antagonize Bcl-2 overexpression. In this study
      we have identified BH3 domain of Bax (Bax BH3) as potentially the best Bcl-2
      antagonist by performing docking of BH3 peptides (peptides representing BH3
      domain of pro-apoptotic and BH3-only proteins) into the Bcl-2 hydrophobic groove
      formed by BH3, BH1 and BH2 domains (also referred as BH3 cleft). To predict the
      best small antagonist for Bcl-2, three groups of small peptides (pentapeptide,
      tetrapeptide and tripeptide) were designed and screened against Bcl-2 which
      revealed the structural importance of a set of residues playing a vital role in
      interaction with Bcl-2. The docking and scoring function identified KRIG and KRI
      as specific peptides among the screened small peptides responsible for Bcl-2
      neutralization and would induce apoptosis. The applied pharmacokinetic and
      pharmacological filters to all small peptides signify that only IGD has drug-like
      properties and displayed good oral bioavailability. However, the obtained binding
      affinity of IGD to Bcl-2 was diminutive. Hence deprotonation, amidation,
      acetylation, benzoylation, benzylation, and addition of phenyl, deoxyglucose and
      glucose fragments were performed to increase the binding affinity and to prevent
      its rapid degradation. Benzoylated IGD tripeptide (IGD(bzo)) was observed to have
      increased binding affinity than IGD with acceptable pharmacokinetic filters. In
      addition, stability of Bcl-2/IGD(bzo) complex was validated by Molecular Dynamics
      (MD) simulations revealing improved binding energy, salt bridges and strong
      interaction energies. This study suggests a new molecule that inhibits Bcl-2
      associated cancer/tumor regression.

PMID- 22155219
TI  - Comparison of ultrasound and X-ray in determining the position of umbilical
      venous catheters.
AB  - OBJECTIVE: Thoraco-abdominal X-ray (TAX) is the most frequent used method to
      determine the route and tip position (TP) of umbilical venous catheters (UVCs).
      The aim of this study was to compare ability of TAX and ultrasonography (US) to
      determine UVC route and TP. PATIENTS AND METHODS: All neonates requiring UVC or
      admitted to our Paediatric and Neonatal Intensive Care with UVC were included in
      this prospective study. Catheter position was controlled by TAX and interpreted
      by the physician in charge of the patient. US examinations were performed by a
      paediatric radiologist blinded to TAX result. The UVC route (central or not
      central) and TP determined by each method were compared to the "actual UVC route
      and TP", as determined by senior paediatric radiologist and neonatologist
      referents joint interpretation of TAX and US results. RESULTS: Sixty-one UVCs
      were assessed in 60 neonates of mean gestational age of 34.7+/-4.2 weeks. To
      determine catheter route, sensitivity and specificity were respectively 96.4% and
      93.9% for US and 92.8% and 78.8% for TAX. To determine catheter tip position,
      sensitivity and specificity were respectively 93.3% and 95.6% for US and 66.7%
      and 63.0% for TAX (p<0.001). Failure of TAX to define UVC tip position increased
      with birth weight (p<0.005). CONCLUSION: TAX and US are reliable in determining
      UVC route (central or not) but US examination is superior to TAX in determining
      UVC TP.

PMID- 22155218
TI  - The effects of exercise on the neuronal response to food cues.
AB  - Increased physical activity is associated with successful long-term weight loss
      maintenance due to mechanisms likely more complex than simply increased energy
      expenditure. The impact of physical activity on the central regulation of food
      intake may be an important mechanism of this effect. The objective of this study
      was to examine the effects of exercise training and acute exercise on the
      neuronal response to food cues as well as eating behaviors. fMRI was performed in
      the fasted state at baseline and again after a 6 month progressive exercise
      intervention (supervised, 5 days/wk) both with and without an acute exercise bout
      in 12 overweight/obese (5 women, 7 men; BMI 33 +/- 4 kg/m(2)) healthy adults.
      fMRI data were acquired while subjects were presented with visual stimuli of
      foods of high hedonic value as compared to neutral control objects.
      Questionnaires on eating behaviors, ratings of appeal and desire for foods, and
      ratings of appetite (hunger, satiety, prospective intake) using visual analog
      scales were also performed at baseline and again after the 6-month exercise
      intervention. While only a trend was observed for a reduction in body weight (102
      +/- 5 to 99 +/- 6 kg, p=0.09), a significant reduction in fat mass was observed
      (36.4 +/- 2.8 to 33.7 +/- 3.2 kg, p=0.04), although as expected changes in fat
      mass were variable (-10.0 to +3.7 kg). Chronic exercise was associated with a
      reduction in the neuronal response to food, primarily in the posterior attention
      network and insula. A significant positive correlation between the change in
      fat/body mass and the change in insula response to food cues with chronic
      exercise was observed. An acute exercise bout attenuated the effects of chronic
      exercise. The exercise intervention, however, did not impact any of the measures
      of appetitive behavior. In summary, despite no effects on behavioral measures of
      appetite, chronic exercise training was associated with attenuation in the
      response to visual food cues in brain regions known to be important in food
      intake regulation. The insula, in particular, appears to play an important role
      in the potential exercise-induced weight loss and weight loss maintenance.

PMID- 22155220
TI  - Mechanisms of the beneficial effect of NHE1 inhibitor in traumatic hemorrhage:
      inhibition of inflammatory pathways.
AB  - This study evaluated the effects of sodium-hydrogen exchanger (NHE1) inhibition
      on enhancing fluid resuscitation outcomes in traumatic hemorrhagic shock, and
      examined the mechanisms related to NHE1 inhibitor-induced protection and recovery
      from hemorrhagic shock. Traumatic hemorrhage was modeled in anesthetized pigs by
      producing tibia fractures followed by hemorrhage of 25 ml/kg for 20 min, and then
      a 4mm hepatic arterial tear with surgical repair after 20 min. Animals then
      underwent low volume fluid resuscitation with either hextend (n=6) or 3mg/kg
      BIIB513 (NHE1 inhibitor)+hextend (n=6). The experiment was terminated 6h after
      the beginning of resuscitation. In association with traumatic hemorrhagic shock,
      there was a decrease in cardiac index, stimulation of the inflammatory response,
      myocardial, liver and kidney injury. The administration of the NHE1 inhibitor at
      the time of resuscitation attenuated shock-resuscitation-induced myocardial
      hypercontracture and resulted in a significant increase in stroke volume index,
      compared to vehicle-treated controls. NHE1 inhibition also reduced the
      inflammatory response, and lessened myocardial, liver and kidney injury. In
      addition, NHE1 inhibition reduced NF-kappaB activation and iNOS expression, and
      attenuated of ERK1/2 phosphorylation. Results from the present study indicate
      that NHE1 inhibition prevents multiple organ injury by attenuating shock
      resuscitation-induced myocardial hypercontracture and by inhibiting NF-kappaB
      activation and neutrophil infiltration, reducing iNOS expression and ERK1/2
      phosphorylation, thereby, reducing systemic inflammation and thus multi-organ
      injury.

PMID- 22155221
TI  - Inhibitory effects of aurentiacin from Syzygium samarangense on
      lipopolysaccharide-induced inflammatory response in mouse macrophages.
AB  - Aurentiacin is a chalcone isolated from Syzygium samarangense. In the present
      study, we examined the anti-inflammatory effects of aurentiacin in
      lipopolysaccharide (LPS)-stimulated mouse macrophages. Aurentiacin significantly
      inhibited LPS-induced nitric oxide (NO) production in RAW264.7 cells
      concomitantly with the suppression of inducible nitric oxide synthase (iNOS)
      expression. Aurentiacin also reduced the mRNA levels of pro-inflammatory
      cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL
      6). Electrophoretic mobility shift assays (EMSAs) and reporter gene assays
      indicated that DNA binding and transcriptional activities of nuclear factor
      kappaB (NF-kappaB)/p65 were decreased by aurentiacin in LPS-stimulated RAW264.7
      cells. Moreover, results from chromatin immunoprecipitation (ChIP) assays over
      the promoter region of the iNOS gene were in agreement with the EMSA results.
      Pretreatment with aurentiacin prevented the nuclear translocation of p65 by
      blocking the phosphorylation of I-kappaB kinase (IKK). Aurentiacin also
      attenuated the phosphorylation (Ser536) and acetylation (Lys310) of p65 and
      phosphorylation of MAPKs. In an inflammatory animal model, the intraperitoneal
      (i.p.) injection of aurentiacin suppressed the release of pro-inflammatory
      cytokines. Moreover, the level of iNOS protein ex vivo was decreased by
      aurentiacin similar to the result in vitro. Taken together, these results suggest
      that aurentiacin shows anti-inflammatory activity related to the inhibition of NF
      kappaB activation.

PMID- 22155217
TI  - The immunological contribution of NF-kappaB within the tumor microenvironment: a
      potential protective role of zinc as an anti-tumor agent.
AB  - Over decades, cancer treatment has been mainly focused on targeting cancer cells
      and not much attention to host tumor microenvironment. Recent advances suggest
      that the tumor microenvironment requires in-depth investigation for understanding
      the interactions between tumor cell biology and immunobiology in order to
      optimize therapeutic approaches. Tumor microenvironment consists of cancer cells
      and tumor associated reactive fibroblasts, infiltrating non-cancer cells,
      secreted soluble factors or molecules, and non-cellular support materials. Tumor
      associated host immune cells such as Th(1), Th(2), Th17, regulatory cells,
      dendritic cells, macrophages, and myeloid-derived suppressor cells are major
      components of the tumor microenvironment. Accumulating evidence suggests that
      these tumor associated immune cells may play important roles in cancer
      development and progression. However, the exact functions of these cells in the
      tumor microenvironment are poorly understood. In the tumor microenvironment, NF
      kappaB plays an important role in cancer development and progression because this
      is a major transcription factor which regulates immune functions within the tumor
      microenvironment. In this review, we will focus our discussion on the
      immunological contribution of NF-kappaB in tumor associated host immune cells
      within the tumor microenvironment. We will also discuss the potential protective
      role of zinc, a well-known immune response mediator, in the regulation of these
      immune cells and cancer cells in the tumor microenvironment especially because
      zinc could be useful for conditioning the tumor microenvironment toward
      innovative cancer therapy.

PMID- 22155222
TI  - Thermolabile antifreeze protein produced in Escherichia coli for structural
      analysis.
AB  - The only hyperactive antifreeze protein (AFP) found to date in fishes is an
      extreme variant of the 3-kDa, alpha-helical, alanine-rich type I AFP, which is
      referred to here as type Ih. Purification of the 33-kDa homodimeric AFP Ih from a
      natural source was hampered by its low levels in fish plasma; by the need to
      remove the more abundant smaller isoforms; and by its extreme thermolability.
      Moreover, ice affinity as a purification tool was spoiled by the tendency of fish
      IgM antibodies to bind to ice in the presence of AFPs. In order to produce enough
      protein for crystallography we expressed AFP Ih as a recombinant protein in the
      Arctic Express(r) strain of Escherichia coli at 12  degrees C, just below the
      thermal denaturation temperature of 16-18  degrees C. His-tags were not useful
      because they compromised the activity and yield of AFP Ih. But in the absence of
      fish antibodies we were able to recover 10-mg quantities of the antifreeze
      protein using two cycles of ice affinity purification followed by anion-exchange
      chromatography to remove contaminating chaperones. The purified recombinant AFP
      Ih yielded diffraction-quality crystals with an extremely asymmetrical unit cell.
      By transferring the genes of the chaperones into a methionine auxotroph we were
      able to grow this host at low temperatures and produce sufficient
      selenomethionine-labeled AFP Ih for crystallography.

PMID- 22155223
TI  - Amino acid-anticodon binding specificity: rationale for a new class of
      therapeutic agent.
AB  - In this article a new class of anticancer and antiviral drugs is discussed. These
      new drugs consist of small di- and tri-peptides, designed to bind to single
      stranded (ss) regions that are crucial for the expression of genes such as the c
      myc oncogene in cancers and start sites (and other ss regions) of viral
      pathogenic genes. The components (i.e. the amino acids and the sequences they
      form) of these peptides could be dictated by the specific binding of amino acids
      to their ss anticodons in tRNA. Cancer cell viability depends on the continued
      overexpression of the c-myc oncogene, and thus this gene is a target of
      opportunity for anticancer agents. Sharply reducing the overexpression of c-myc
      leads to the death of cancer cells. To achieve this end the following rationale
      is suggested: crucial regions of the c-myc promoters (to which activating
      proteins must bind for expression to occur) are single stranded and thus strongly
      resemble the anticodon loop of tRNA. It was found that amino acids chemically
      bind to their cognate tRNA anticodons. Regarding the ss regions of c-myc as a
      series of adjacent 'anticodons', di- and tri-peptides are proposed to be aligned
      to their cognate 'anticodons' in the proper order. For example, if the ss region
      of a promoter is hypothetically TTT-GGG-CCC, the tripeptide Lys-Pro-Gly could be
      expected to bind to it and deny access of the promoter to all activating
      proteins, thereby blocking c-myc expression and all the cancers dependent on such
      overexpression. Similarly, it is reported that in the initial phase of gene
      expression the start sites of the genes are single stranded (before and after and
      spanning the start site). Thus, invoking the amino acid cognate anticodon binding
      specificity (ACABS) principle as described above, a series of small peptides are
      suggested that could span the start sites of pathogenic viral genes (e.g. the
      oris region of herpes simplex virus (HSV)) to deny access of the gene to the
      transcription elements. This would inactivate the toxic effect of the virus and
      thereby constitute a promising approach to antiviral therapy, where the start
      sites (or other ss regions of pathogenic genes) have been sequenced. The ACABS
      principle (for peptide-nucleic-acid interaction) enables us to focus on probable
      effective small peptides rather than having to screen a large number of randomly
      chosen small peptides to find probable anticancer and antiviral therapeutic
      agents.

PMID- 22155224
TI  - A network-based approach to quantifying the impact of biologically active
      substances.

PMID- 22155225
TI  - Target validation.

PMID- 22155226
TI  - Dysphagia after anterior cervical spine surgery: incidence and risk factors.
AB  - OBJECTIVE: To evaluate risk factors for the development of dysphagia after
      anterior cervical surgery. METHODS: The records of 249 patients who underwent
      anterior cervical surgery were reviewed. The presence and severity of dysphagia
      were assessed with the Dysphagia Disability Index 6 weeks and 3, 6, and 12 months
      after surgery. Age; sex; ethnicity; cigarette smoking; previous cervical
      surgeries; reoperation for same pathology; type of procedure, incision, and
      instrumentation; number and levels involved; side of procedure, length of
      surgery; and use of postoperative bracing were analyzed. RESULTS: During the
      first 6 months after surgery, 27 (10.8%) patients developed dysphagia. From these
      patients the presence of dysphagia at 6 weeks and at 3 and 6 months was 88.8%,
      29.6%, and 7.4%, respectively. By 12 months, dysphagia had resolved in all cases.
      The mean age of patients with dysphagia was 55 years (SD 12.98) and 50 years (SD
      12.07) in patients without dysphagia (P = 0.05). Dysphagic patients had an
      average of 2.2 (SD 1.15) levels operated compared with 1.84 (SD 0.950) in
      nondysphagic patients (P = 0.05). Patients who developed dysphagia were most
      often treated at C4-5 (67%) and C5-6 (81%: P < 0.001). Although mean operative
      time was slightly longer in patients with dysphagia (186 minutes) compared with
      those without (169 minutes), the difference was not significant. CONCLUSIONS: In
      our patients, the incidence of dysphagia was low, and it had completely resolved
      at 12 months in all cases. Risk factors for dysphagia were multilevel procedures,
      involvement of C4-5 and C5-6, and age.

PMID- 22155227
TI  - The developmental neurotoxicity of organophosphorus insecticides: a direct role
      for the oxon metabolites.
AB  - Several extensively used organophosphorus ester (OP) insecticides are
      phosphorothionates. The oxon metabolites of phosphorothionates have long been
      known to be responsible for the acute cholinergic neurotoxicity associated with
      OP poisoning. In addition, there is now sufficient evidence to suggest that the
      oxon metabolites may also be directly responsible for the particular
      neurotoxicity that phosphorothionate insecticides, and especially chlorpyrifos
      (CP) and diazinon (DZ), are known to inflict on the developing organism. In vitro
      data reveal that the oxons, which are present at increased levels in the
      developing brain, have the ability to directly disrupt, at toxicologically
      relevant doses, separately a number of neurodevelopmental processes, including
      those of neuronal proliferation, neuronal differentiation, gliogenesis and
      apoptosis. In most cases, the effects of the oxons are very potent. Inhibition of
      neuronal and glial cell differentiation by the oxons in particular is up to 1000
      times stronger than that caused by their parent phosphorothionates. The
      neurodevelopmental toxicity of the oxons is not related to the inhibition of the
      enzymatic activity of acetylcholinesterase (AChE), but may be due to direct oxon
      interference with the morphogenic activity that AChE normally shows during
      neurodevelopment. Other possible direct targets of the oxons include
      neurodevelopmentally important cell signaling molecules and cytoskeletal proteins
      which have been found to be affected by the oxons and to which covalent binding
      of the oxons has been recently shown. Future studies should aim at confirming the
      developmental neurotoxic capacity of the oxons under in vivo conditions and they
      must also be extended to include OP parent insecticides with a P=O moiety.

PMID- 22155228
TI  - Regulation of adiponectin secretion by soy isoflavones has implication for
      endocrine function of the testis.
AB  - Testicular Leydig cells are the predominant source of the male sex steroid
      hormone testosterone (T), which is required to maintain male fertility. There is
      now growing evidence that environmental stressors, including chemicals present in
      food, air and water, may affect energy balance. A relationship between energy
      balance and reproductive capacity has been proposed for a long time. In the
      present study, developmental exposures of male rats to soy isoflavones in the
      maternal diet from gestational day 12 to day 21 post-partum enhanced adiponectin
      expression in adipose tissue and increased serum adiponectin concentrations in
      adulthood. However, exposure to soy isoflavones caused a decrease in T production
      and expression of adiponectin and its receptor (adipoR2) in Leydig cells. In
      separate experiments, incubation of Leydig cells with recombinant adiponectin in
      the absence of isoflavones caused a decrease in T biosynthesis associated with
      diminished expression of the cholesterol transporter steroidogenic acute
      regulatory protein (StAR). Thus, chemical-induced alterations in serum
      adiponectin concentrations have implication for steroid hormone secretion. The
      results also imply that changes in adipose tissue metabolism occasioned by
      exposure to dietary estrogens, and perhaps other estrogenic agents, possibly
      contribute to deficiencies in reproductive capacity attributed to these
      compounds.

PMID- 22155229
TI  - The role of Roquin overexpression in the modulation of signaling during in vitro
      and ex vivo T-cell activation.
AB  - The T-cell receptor (TCR) engages with an antigen and initiates a signaling
      cascade that leads to the activation of transcription factors. Roquin, a protein
      encoded by the RC3H1 gene and characterized as an immune regulator, was recently
      identified as a novel RING-type ubiquitin ligase family member, but the
      mechanisms by which Roquin regulates T-cell responses are unclear. We used the EL
      4 murine lymphoma cell line to elucidate the role of Roquin in vitro. Roquin
      overexpressing EL-4 cells became hyper-responsive after anti-CD3/CD28 stimulation
      in vitro and were a major source of the cytokines IL-2 and TNF-alpha. Upon
      activation, these cells showed particularly enhanced production of IL-2 and TNF
      alpha. To clarify the important role played by Roquin in T-cell responses ex
      vivo, we generated T-cell-specific Roquin transgenic (Tg) mice. Roquin-Tg CD4(+)
      T-cells showed enhanced production of IL-2 and TNF-alpha in response to TCR
      stimulation with anti-CD28 co-stimulation. Further studies are necessary to
      investigate the role of Roquin in the regulation of primary T-cell activation,
      survival, and differentiation.

PMID- 22155230
TI  - Osteopontin is critical to determine symptom severity of influenza through the
      regulation of NK cell population.
AB  - Osteopontin (OPN) is involved in exacerbating various inflammatory diseases. A
      severe pulmonary inflammation is frequently found in lethal influenza A virus
      (IAV) infection. However, the function of OPN against the infection was poorly
      understood. Here, we demonstrate an importance of OPN on immune response and
      disease severity after IAV infection. We found that the expression level of OPN
      was increased in mice infected with IAV. The OPN knockout (KO) mice exhibited a
      severe pathological phenotype and the survival rate decreased after the lethal
      IAV infection, compared to the wild type mice, while the survival rate increased
      in OPN transgenic (Tg) mice. The population of natural killer (NK) cells
      significantly decreased in OPN KO mice at day 5 after the infection, whereas, it
      increased in OPN Tg mice. These results suggest that OPN plays an important role
      in host defense against IAV infection through the regulation of NK cell
      population.

PMID- 22155231
TI  - The Brucella TIR-like protein TcpB interacts with the death domain of MyD88.
AB  - The pathogen Brucella melitensis secretes a Toll/interleukin-1 receptor (TIR)
      domain containing protein that abrogates host innate immune responses. In this
      study, we have characterized the biochemical interactions of Brucella TIR-like
      protein TcpB with host innate immune adaptor proteins. Using protein-fragment
      complementation assays based on Gaussia luciferase and green fluorescent protein,
      we find that TcpB interacts directly with MyD88 and that this interaction is
      significantly stronger than the interaction of TcpB with TIRAP, the only other
      adaptor protein that detectably interacts with TcpB. Surprisingly, the TcpB-MyD88
      interaction depends on the death domain (DD) of MyD88, and TcpB does not interact
      with the isolated TIR domain of MyD88. TcpB disrupts MyD88(DD)-MyD88(DD),
      MyD88(DD)-MyD88(TIR) and MyD88(DD)-MyD88 interactions but not MyD88-MyD88 or
      MyD88(TIR)-MyD88(TIR) interactions. Structural models consistent with these
      results suggest how TcpB might inhibit TLR signaling by targeting MyD88 via a DD
      TIR domain interface.

PMID- 22155232
TI  - c-Jun N-terminal kinase 2 phosphorylates endothelial nitric oxide synthase at
      serine 116 and regulates nitric oxide production.
AB  - The c-Jun N-terminal kinases (JNKs) belonging to the mitogen-activated protein
      kinase (MAPK) superfamily play important roles in foam-cell formation,
      hypercholesterolemia-mediated endothelial dysfunction, and the development of
      obesity. Although decreased nitric oxide (NO) production via decreased
      phosphorylation of endothelial NO synthase at serine 1179 (eNOS-Ser(1179)) was
      reported to be partly involved in JNK2-derived endothelial dysfunction, JNK2
      seems likely to be indirectly involved in this signaling pathway. Here, using
      bovine aortic endothelial cells, we examined whether JNK2 directly phosphorylated
      eNOS-Ser(116), a putative substrate site for the MAPK superfamily, and this
      phosphorylation resulted in decreased NO release. JNK inhibitor SP60012 increased
      NO release in a time- and dose-dependent manner, which was accompanied by
      increased eNOS-Ser(116) phosphorylation. Purified JNK2 directly phosphorylated
      eNOS-Ser(116)in vitro. Ectopic expression of dominant negative JNK2 repressed
      eNOS-Ser(116) phosphorylation and increased NO production. Coimmunoprecipitation
      and confocal microscopy studies revealed a colocalization of eNOS and JNK2.
      However, all these observed effects were not manifested when JNK1 probes were
      used. Overall, this study indicates that JNK2 is a physiological kinase
      responsible for eNOS-Ser(116) phosphorylation and regulates NO production.

PMID- 22155233
TI  - Influence of drying on the secondary structure of intrinsically disordered and
      globular proteins.
AB  - Circular dichroism (CD) spectroscopy of five Arabidopsis late embryogenesis
      abundant (LEA) proteins constituting the plant specific families LEA_5 and LEA_6
      showed that they are intrinsically disordered in solution and partially fold
      during drying. Structural predictions were comparable to these results for
      hydrated LEA_6, but not for LEA_5 proteins. FTIR spectroscopy showed that
      verbascose, but not sucrose, strongly affected the structure of the dry proteins.
      The four investigated globular proteins were only mildly affected by drying in
      the absence, but strongly in the presence of sugars. These data highlight the
      larger structural flexibility of disordered compared to globular proteins and the
      impact of sugars on the structure of both disordered and globular proteins during
      drying.

PMID- 22155234
TI  - Autophagy regulates inflammation in adipocytes.
AB  - Autophagy is an essential process for both the maintenance and the survival of
      cells, with homeostatic low levels of autophagy being critical for intracellular
      organelles and proteins. In insulin resistant adipocytes, various
      dysfunctional/damaged molecules, organelles, proteins, and end-products
      accumulate. However, the role of autophagy (in particular, whether autophagy is
      activated or not) is poorly understood. In this study we found that in adipose
      tissue of insulin resistant mice and hypertrophic 3T3-L1 adipocytes autophagy was
      suppressed. Also in hypertrophic adipocytes, autophagy-related gene expression,
      such as LAMP1, LAMP2, and Atg5 was reduced, whereas gene expression in the
      inflammatory-related genes, such as MCP-1, IL-6, and IL-1beta was increased. To
      find out whether suppressed autophagy was linked to inflammation we used the
      autophagy inhibitor, 3-methyladenine, to inhibit autophagy. Our results suggest
      that such inhibition leads to an increase in inflammatory gene expression and
      causes endoplasmic reticulum (ER) stress (which can be attenuated by treatment
      with the ER stress inhibitor, Tauroursodeoxycholic Acid). Conversely, the levels
      of inflammatory gene expression were reduced by the activation of autophagy or by
      the inhibition of ER stress. The results indicate that the suppression of
      autophagy increases inflammatory responses via ER stress, and also defines a
      novel role of autophagy as an important regulator of adipocyte inflammation in
      systemic insulin resistance.

PMID- 22155235
TI  - Cellular localization of dopamine receptors in the gastric mucosa of rats.
AB  - Dopamine (DA) plays a critical role in the protection of gastric mucosa and is
      mediated through corresponding receptors. However, the details of the expression
      of DA receptors (D1-D5) in the gastric mucosa are lacking. The present study
      investigated the expression and cellular localization of DA receptors in rat
      gastric mucosa by means of real-time PCR and immunofluorescent techniques. The
      results indicated that the mRNA expressions of all five subtypes of DA receptors
      were found in the gastric mucosa, among which the D2 level was the highest. The
      immunopositive cells of D1-D3 and D5 were primarily localized to the basilar
      gland of the epithelial layer in gastric corpus, but D4 immunoreactivity (IR) was
      only observed in the enteric nerve plexus. The D1, D2, and D5 IR were found in
      pepsin C-IR cells except D3. No IR of any DA receptor was detected in the
      H(+)/K(+)-ATPase- or mucin 6-IR cells. In conclusion, for the first time, this
      study demonstrates the predominant distribution of DA receptors in the chief
      cells, not the parietal and mucous neck cells, in rat gastric mucosa, thus
      suggesting that DA may not directly regulate the function of parietal cells or
      mucous neck cells, but it may modulate the function of chief cells through the
      D1, D2, and D5 receptors.

PMID- 22155236
TI  - Theaflavin attenuates ischemia-reperfusion injury in a mouse fatty liver model.
AB  - The incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing,
      and there is a shortage of liver donors, which has led to the acceptance of
      steatotic livers for transplantation. However, steatotic livers are known to
      experience more severe acute ischemia-reperfusion (I/R) injury than normal livers
      upon transplantation. In the present study, we investigated the role of
      theaflavin, a polyphenol substance extracted from black tea, in attenuating acute
      I/R injury in a fatty liver model. We induced I/R in normal and steatotic livers
      treated with or without theaflavin. We also separated primary hepatocytes from
      the normal and steatotic livers, and applied RAW264.7 cells, a mouse macrophage
      cell line, that was pretreated with theaflavin. We observed that liver steatosis,
      oxidative stress, inflammation and hepatocyte apoptosis were increased in the
      steatotic liver compared to the normal liver, however, these changes were
      significantly decreased by theaflavin treatment. In addition, theaflavin
      significantly diminished the ROS production of steatotic hepatocytes and TNF
      alpha production by LPS-stimulated RAW264.7 cells. We concluded that theaflavin
      has protective effects against I/R injury in fatty livers by anti-oxidant, anti
      inflammatory, and anti-apoptotic mechanisms.

PMID- 22155237
TI  - The human phospholamban Arg14-deletion mutant localizes to plasma membrane and
      interacts with the Na/K-ATPase.
AB  - Depressed Ca-handling in cardiomyocytes is frequently attributed to impaired
      sarcoplasmic reticulum (SR) function in human and experimental heart failure.
      Phospholamban (PLN) is a key regulator of SR and cardiac function, and PLN
      mutations in humans have been associated with dilated cardiomyopathy (DCM). We
      previously reported the deletion of the highly conserved amino acid residue
      arginine 14 (nucleic acids 39, 40 and 41) in DCM patients. This basic amino acid
      is important in maintaining the upstream consensus sequence for PKA
      phosphorylation of Ser 16 in PLN. To assess the function of this mutant PLN, we
      introduced the PLN-R14Del in cardiac myocytes of the PLN null mouse. Transgenic
      lines expressing mutant PLN-R14Del at similar protein levels to wild types
      exhibited no inhibition of the initial rates of oxalate-facilitated SR Ca uptake
      compared to PLN-knockouts (PLN-KO). The contractile parameters and Ca-kinetics
      also remained highly stimulated in PLN-R14Del cardiomyocytes, similar to PLN-KO,
      and isoproterenol did not further stimulate these hyper-contractile basal
      parameters. Consistent with the lack of inhibition on SR Ca-transport and
      contractility, confocal microscopy indicated that the PLN-R14Del failed to co
      localize with SERCA2a. Moreover, PLN-R14Del did not co-immunoprecipitate with
      SERCA2a (as did WT-PLN), but rather co-immunoprecipitated with the sarcolemmal
      Na/K-ATPase (NKA) and stimulated NKA activity. In addition, studies in HEK cells
      indicated significant fluorescence resonance energy transfer between PLN-R14Del
      YFP and NKAalpha1-CFP, but not with the NKA regulator phospholemman. Despite the
      enhanced cardiac function in PLN-R14Del hearts (as in PLN-knockouts), there was
      cardiac hypertrophy (unlike PLN-KO) coupled with activation of Akt and the MAPK
      pathways. Thus, human PLN-R14Del is misrouted to the sarcolemma, in the absence
      of endogenous PLN, and alters NKA activity, leading to cardiac remodeling.

PMID- 22155238
TI  - Soluble epoxide hydrolase inhibition improves myocardial perfusion and function
      in experimental heart failure.
AB  - The study addressed the hypothesis that soluble epoxide hydrolase (sEH)
      inhibition, which increases cardiovascular protective epoxyeicosatrienoic acids
      (EETs), exerts beneficial effects in an established chronic heart failure (CHF)
      model. In CHF rats, left ventricular (LV) function, perfusion and remodeling were
      assessed using MRI and invasive hemodynamics after 42-day (starting 8 days after
      coronary ligation) and delayed 3-day (starting 47 days after coronary ligation)
      treatments with the sEH inhibitor AUDA (twice 0.25 mg/day). Delayed 3-day and 42
      day AUDA increased plasma EETs demonstrating the effective inhibition of sEH.
      Delayed 3-day and 42-day AUDA enhanced cardiac output without change in arterial
      pressure, thus reducing total peripheral resistance. Both treatment periods
      increased the slope of the LV end-systolic pressure-volume relation, but only 42
      day AUDA decreased LV end-diastolic pressure, relaxation constant Tau and the
      slope of the LV end-diastolic pressure-volume relation, associated with a reduced
      LV diastolic volume and collagen density. Delayed 3-day and, to a larger extent,
      42-day AUDA increased LV perfusion associated with a decreased LV hypoxia
      inducible factor-1alpha. Both treatment periods decreased reactive oxygen species
      level and increased reduced-oxidized glutathione ratio. Finally, MSPPOH, an
      inhibitor of the EET-synthesizing enzyme cytochrome epoxygenases, abolished the
      beneficial effects of 3-day AUDA on LV function and perfusion. Augmentation of
      EET availability by pharmacological inhibition of sEH increases LV diastolic and
      systolic functions in established CHF. This notably results from short-term
      processes, i.e. increased LV perfusion, reduced LV oxidative stress and
      peripheral vasodilatation, but also from long-term effects, i.e. reduced LV
      remodeling.

PMID- 22155239
TI  - Structural basis of anthrax edema factor neutralization by a neutralizing
      antibody.
AB  - Fine epitope mapping of EF13D, a highly potent neutralizing monoclonal antibody
      specific for the anthrax edema factor (EF), was accomplished through random
      mutagenesis and yeast surface display. A yeast-displayed library of single point
      mutants of an EF domain III (DIII), comprising amino acids 624-800, was
      constructed by random mutagenesis and screened for reduced binding to EF13D. With
      this method, residues Leu 667, Ser 668, Arg 671, and Arg 672 were identified as
      key residues important for EF13D binding. They form a contiguous patch on a
      solvent-exposed surface at one end of the four-helix bundle of DIII.
      Computational protein-protein docking experiments between anEF13D model and a
      crystal structure of EF indicate that the EF13D heavy chain complementarity
      determining region 3 (HCDR3) is deeply buried within a hydrophobic cleft between
      two helices of DIII and interacts directly with residues Leu 667, Ser 668, Arg
      671 and Arg 672, providing an explanation for the high binding affinity. In
      addition, they show that the HCDR3 binding site overlaps with the binding site of
      the N-terminal lobe of calmodulin (CaM), an EF enzymatic activator, consistent
      with a previous finding showing direct competition with CaM that results in
      neutralization of EF. Identifying the neutralization epitope of EF13D on EF
      improves our understanding of the neutralization mechanism and has implications
      for vaccine development.

PMID- 22155240
TI  - Phenylenediamine derivatives induce GDF-15/MIC-1 and inhibit adipocyte
      differentiation of mouse 3T3-L1 cells.
AB  - Phenylenediamine derivatives can function as a hydrogen donor and reportedly
      exert various biological actions including cytoprotective effects against
      oxidative stress, possibly by acting as an antioxidant. Previous studies showed
      that feeding of such compounds to mice reduced their body weight, but the precise
      mechanism remains unknown at present. Here, we found that these compounds
      inhibited the in vitro differentiation of mouse preadipocytes, 3T3-L1 cells, into
      adipocytes, suggesting that, at least in part, reduced generation of adipocytes
      might contribute to the observed weight loss in mice. Next, we performed array
      analysis and found that the expression of GDF-15/MIC-1, which is a TGFbeta
      superfamily cytokine, and Trib 3, an intracellular downstream effector of the
      cytokines, was up-regulated by these derivatives. Thus, we identified the
      compounds as inducers of GDF-15/MIC-1 and suggest that such induction may have
      led to inhibition of adipocyte differentiation, which could account for the
      weight-loss effect of these compounds.

PMID- 22155241
TI  - Diverse biological activities of the vascular non-inflammatory molecules - the
      Vanin pantetheinases.
AB  - The Vanin genes are a family that encode pantetheinases involved in recycling
      Coenzyme A, catalysing the breakdown of intermediate pantetheine to vitamin B5
      for reuse in CoA biosynthesis. The role of pantetheinase in this most fundamental
      of cellular processes, was substantially characterised by the 1970s. The next 20
      years saw little further interest in pantetheinase until various genetic studies
      implicated the Vanin locus in a range of normal and disease phenotypes, and a
      consequent interest in the other product of pantetheinase activity, cysteamine.
      This report seeks to bring together the early biochemical studies with recent
      biological data implicating cysteamine as a regulator of the oxidative state of a
      cell. Numerous studies now report a role for Vanin in inflammation, oxidative
      stress, cell migration and numerous diseases including cardiovascular disease.

PMID- 22155242
TI  - G-protein-coupled receptor GPR21 knockout mice display improved glucose tolerance
      and increased insulin response.
AB  - GPR21 is an orphan G-protein-coupled receptor. We found that mice deficient for
      the GPR21 gene were resistant to diet-induced obesity. Knockout mice were leaner
      than their wildtype counterpart, despite that no difference was observed in food
      intake. No differences were observed in the respiratory exchange rate and
      thermogenesis. However, knockout mice were more active than wildtype littermates,
      and this level of activity may be an underlying reason for the difference in
      energy balance. Mutant mice were more sensitive to insulin than their wildtype
      control and showed an improved glucose tolerance. Several inflammatory markers
      MCP-1, CRP and IP-10 were decreased in mutant animals, suggesting that GPR21 may
      also mediate its effect through anti-inflammatory mechanisms. We found that GPR21
      is widely expressed in all tissues, with the highest levels found in the brain
      and in the spleen. Overall, these findings suggest that GPR21 may play an
      important role in regulating body weight and glucose metabolism.

PMID- 22155243
TI  - Decreased expression of endoplasmic reticulum chaperone GRP78 in liver of
      diabetic mice.
AB  - To identify molecular targets associated with the development of diabetes, we
      analyzed the hepatic proteome of obese diabetic db/db mice using electrophoresis
      on a high-resolution two-dimensional gel combined with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. By comparison between non
      diabetic db/+ and diabetic db/db mice, six proteins and one protein were
      significantly decreased and increased in the diabetic mice, respectively. Among
      these proteins, two of the decreased proteins are involved in endoplasmic
      reticulum (ER) stress-related unfolded protein response, GRP78 and protein
      disulfide isomerase A3, and it was revealed that the decreased GRP78 expression
      in the liver of diabetic db/db mice is due to the reduction of GRP78 protein
      synthesis rather than RNA transcription. In addition, we found that the treatment
      of human hepatocyte HepG2 cells with oleic acid decreased the expression of
      GRP78, and attenuated the activation of AKT by insulin stimulation. These results
      suggest that decreased GRP78 expression may induce resistance to insulin by
      inhibiting the AKT activation, and plays an important role in the development of
      type 2 diabetes.

PMID- 22155244
TI  - Oxygen tension regulates the osteogenic, chondrogenic and endochondral phenotype
      of bone marrow derived mesenchymal stem cells.
AB  - The local oxygen tension is a key regulator of the fate of mesenchymal stem cells
      (MSCs). The objective of this study was to investigate the effect of a low oxygen
      tension during expansion and differentiation on the proliferation kinetics as
      well as the subsequent osteogenic and chondrogenic potential of MSCs. We first
      hypothesised that expansion in a low oxygen tension (5% pO(2)) would improve both
      the subsequent osteogenic and chondrogenic potential of MSCs compared to
      expansion in a normoxic environment (20% pO(2)). Furthermore, we hypothesised
      that chondrogenic differentiation in a low oxygen environment would suppress
      hypertrophy of MSCs cultured in both pellets and hydrogels used in tissue
      engineering strategies. MSCs expanded at 5% pO(2) proliferated faster forming
      larger colonies, resulting in higher cell yields. Expansion at 5% pO(2) also
      enhanced subsequent osteogenesis of MSCs, whereas differentiation at 5% pO(2) was
      found to be a more potent promoter of chondrogenesis than expansion at 5% pO(2).
      Greater collagen accumulation, and more intense staining for collagen types I and
      X, was observed in pellets maintained at 20% pO(2) compared to 5% pO(2). Both
      pellets and hydrogels stained more intensely for type II collagen when undergoing
      chondrogenesis in a low oxygen environment. Differentiation at 5% pO(2) also
      appeared to inhibit hypertrophy in both pellets and hydrogels, as demonstrated by
      reduced collagen type X and Alizarin Red staining and alkaline phosphatase
      activity. This study demonstrates that the local oxygen environment can be
      manipulated in vitro to either stabilise a chondrogenic phenotype for use in
      cartilage repair therapies or to promote hypertrophy of cartilaginous grafts for
      endochondral bone repair strategies.

PMID- 22155245
TI  - Silencing of cancer-germline genes in human preimplantation embryos: evidence for
      active de novo DNA methylation in stem cells.
AB  - Several human germline-specific genes rely principally on DNA methylation for
      repression in somatic tissues. Many of these genes, including MAGEA1, were
      qualified as cancer-germline (CG), as they become activated in tumors, where
      losses of DNA methylation are common. The developmental stage at which CG genes
      acquire DNA methylation marks is unknown. Here, we show that in human
      preimplantation embryos, transcription of CG genes increases up to the morula
      stage, and then decreases dramatically in blastocysts, suggesting that CG gene
      silencing occurs in blastocyst stem cells. Consistently, transfection studies
      with MAGEA1 constructs in embryonal carcinoma (EC) cells, which represent a
      malignant surrogate of blastocyst-derived stem cells, revealed active repression
      and marked de novo methylation of MAGEA1 transgenes in these cells. Active
      repression of the endogenous MAGEA1 gene in human EC cells was evidenced by its
      rapid re-silencing following prior induction with a DNA methylation inhibitor.
      Moreover, de novo DNA methyltransferases DNMT3A and DNMT3B appeared to contribute
      to the silencing of MAGEA1 and other CG genes in EC cells. Altogether our data
      indicate that CG genes like MAGEA1 are programmed for repression in the
      blastocyst, and suggest that de novo DNA methylation is a key event in this
      process.

PMID- 22155246
TI  - Mutagenesis by imprecise excision of the piggyBac transposon in Drosophila
      melanogaster.
AB  - Mutagenesis by transposon-mediated imprecise excision is the most extensively
      used technique for mutagenesis in Drosophila. Although P-element is the most
      widely used transposon in Drosophila to generate deletion mutants, it is limited
      by the insertion coldspots in the genome where P-elements are rarely found. The
      piggyBac transposon was developed as an alternative mutagenic vector for
      mutagenesis of non-P-element targeted genes in Drosophila because the piggyBac
      transposon can more randomly integrate into the genome. Previous studies
      suggested that the piggyBac transposon always excises precisely from the
      insertion site without initiating a deletion or leaving behind an additional
      footprint. This unique characteristic of the piggyBac transposon facilitates
      reversible gene-transfer in several studies, such as the generation of induced
      pluripotent stem (iPS) cells from fibroblasts. However, it also raised a
      potential limitation of its utility in generating deletion mutants in Drosophila.
      In this study, we report multiple imprecise excisions of the piggyBac transposon
      at the sepiapterin reductase (SR) locus in Drosophila. Through imprecise excision
      of the piggyBac transposon inserted in the 5'-UTR of the SR gene, we generated a
      hypomorphic mutant allele of the SR gene which showed markedly decreased levels
      of SR expression. Our finding suggests that it is possible to generate deletion
      mutants by piggyBac transposon-mediated imprecise excision in Drosophila.
      However, it also suggests a limitation of piggyBac transposon-mediated reversible
      gene transfer for the generation of induced pluripotent stem (iPS) cells.

PMID- 22155247
TI  - Calcium signalling in adult endothelial outgrowth cells.
AB  - Endothelial outgrowth cells (EOCs) derived from blood mononuclear cells can
      differentiate to an endothelial-like phenotype. There are deficits in
      understanding of the biology of these cells, particularly detailed
      characterisation of their Ca(2+) signalling mechanisms. In the current study, it
      was found that human EOCs express two forms of ryanodine receptor (RyR1 and RyR2)
      Ca(2+) release channel in their endoplasmic reticulum. Individual EOCs display
      heterogeneous Ca(2+) responses to physiologically relevant regulators fibrinogen
      and collagen. Some EOCs showed distinctive, multiphasic Ca(2+) responses to
      fibrinogen consisting of rapid decreases, transient increases then a gradual
      return to the resting levels. Transient elevations in Ca(2+) required both L-type
      voltage gated calcium channels and RyRs. Decreases in Ca(2+) stimulated by
      fibrinogen depended on plasma membrane Ca(2+) ATPase pumps, but did not require
      thapsigargin-sensitive Ca(2+) ATPases. These results indicate that EOCs possess
      sophisticated Ca(2+) signalling mechanisms, capable of generating distinct Ca(2+)
      waveforms in response to different physiologically relevant cues.

PMID- 22155248
TI  - Sulfated, low molecular weight lignins inhibit a select group of heparin-binding
      serine proteases.
AB  - Sulfated low molecular weight lignins (LMWLs), designed as oligomeric mimetics of
      low molecular weight heparins (LMWHs), have been found to bind in exosite II of
      thrombin. To assess whether sulfated LMWLs recognize other heparin-binding
      proteins, we studied their effect on serine proteases of the coagulation,
      inflammatory and digestive systems. Using chromogenic substrate hydrolysis assay,
      sulfated LMWLs were found to potently inhibit coagulation factor XIa and human
      leukocyte elastase, moderately inhibit cathepsin G and not inhibit coagulation
      factors VIIa, IXa, and XIIa, plasma kallikrein, activated protein C, trypsin, and
      chymotrypsin. Competition studies show that UFH competes with sulfated LMWLs for
      binding to factors Xa and XIa. These results further advance the concept of
      sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based
      on their novel scaffold.

PMID- 22155249
TI  - The MgtR regulatory peptide negatively controls expression of the MgtA Mg2+
      transporter in Salmonella enterica serovar Typhimurium.
AB  - MgtR is a 30 amino acid peptide that is encoded from the mgtCBR operon. This
      peptide has recently been demonstrated to interact with the MgtC virulence
      protein and lead to MgtC degradation. In the present study, we reveal that the
      MgtA Mg(2+) transporter is another protein under the direct control of the MgtR
      peptide. Salmonella expresses the MgtA transporter only in Mg(2+) depleted
      conditions. We determined that the MgtR peptide limits levels of the MgtA protein
      at low Mg(2+) concentrations. MgtA expression increased in a Salmonella strain
      lacking MgtR but decreased in a strain overexpressing MgtR. Moreover, we found
      that the MgtR peptide is necessary for the MgtA protein to be induced at the
      normal timing upon Mg(2+) starvation. The MgtR peptide did not affect
      transcription of the mgtA gene but specifically bound to the MgtA transporter in
      vivo, resembling the features of MgtR-regulated MgtC expression. MgtR-mediated
      regulation of MgtA expression was biologically significant because the lack of
      MgtR enhanced Salmonella growth in low Mg(2+).

PMID- 22155250
TI  - Functional analysis of alpha1,3/4-fucosyltransferase VI in human hepatocellular
      carcinoma cells.
AB  - The alpha1,3/4-fucosyltransferases (FUT) subfamily are key enzymes in cell
      surface antigen synthesis during various biological processes. A novel role of
      FUTs in tumorigenesis has been discovered recently, however, the underlying
      mechanism remains largely unknown. Here, we characterized FUT6, a member of
      alpha1,3/4-FUT subfamily, in human hepatocellular carcinoma (HCC). In HCC
      tissues, the expression levels of FUT6 and its catalytic product SLe(x) were
      significantly up-regulated. Overexpression of FUT6 in HCC cells enhanced S-phase
      cell population, promoted cell growth and colony formation ability. Moreover,
      subcutaneously injection of FUT6-overexpressing cells in nude mice promoted cell
      growth in vivo. In addition, elevating FUT6 expression markedly induced
      intracellular Akt phosphorylation, and suppressed the expression of the cyclin
      dependent kinases inhibitor p21. Bath application of the PI3K inhibitor blocked
      FUT6-induced Akt phosphorylation, p21 suppression and cell proliferation. Our
      results suggest that FUT6 plays an important role in HCC growth by regulating the
      PI3K/Akt signaling pathway.

PMID- 22155251
TI  - A mechanism of action for small heat shock proteins.
AB  - Molecular dynamics simulations of a fitted multimeric structure of Mycobacterium
      tuberculosis alpha-crystallin (Mtb Acr) identify solvent exclusion from the
      beta(4)-beta(8) hydrophobic groove as a critical factor driving subunit assembly.
      Dehydration is also implicated as a determinant factor governing the chaperone
      activity of the dimer upon its dissociation from the oligomer. Two exposed
      hydrogen bonds, responsible for stabilizing the beta(8)-beta(9) fold are
      identified as key mechanistic elements in this process. Based on the
      overproduction of the chemokine CXCL16, observed after macrophage exposure to Mtb
      Acr, the proteases ADAM10 and ADAM17 are mooted as possible targets of this
      chaperone activity.

PMID- 22155252
TI  - A natural small molecule voacangine inhibits angiogenesis both in vitro and in
      vivo.
AB  - Angiogenesis, the formation of new blood vessels from pre-existing ones, plays a
      critical role in normal and pathological phenotypes, including solid tumor growth
      and metastasis. Accordingly, the development of new anti-angiogenic agents is
      considered an efficient strategy for the treatment of cancer and other human
      diseases linked with angiogenesis. We have identified voacangine, isolated from
      Voacanga africana, as a novel anti-angiogenic agent. Voacangine inhibits the
      proliferation of HUVECs at an IC(50) of 18 MUM with no cytotoxic effects.
      Voacangine significantly suppressed in vitro angiogenesis, such as VEGF-induced
      tube formation and chemoinvasion. Moreover, the compound inhibits in vivo
      angiogenesis in the chorioallantoic membrane at non-toxic doses. In addition,
      voacangine decreased the expression levels of hypoxia inducible factor-1alpha and
      its target gene, VEGF, in a dose-dependent manner. Taken together, these results
      suggest that the naturally occurring compound, voacangine, is a novel anti
      angiogenic compound.

PMID- 22155253
TI  - The expression and function of vascular endothelial growth factor in retinal
      pigment epithelial (RPE) cells is regulated by 4-hydroxynonenal (HNE) and
      glutathione S-transferaseA4-4.
AB  - It is well established that 4-hydroxynonenal (HNE) plays a major role in
      oxidative stress-induced signaling and the toxicity of oxidants. Surprisingly our
      recent studies also demonstrate that low levels of HNE generated during oxidative
      stress promote cell survival mechanisms and proliferation. Since the expression
      and secretion of VEGF is known to be affected by Oxidative stress, during present
      studies, we have examined dose dependent effect of HNE on VEGF expression and
      secretion in a model of retinal pigment epithelial (RPE) cells in culture.
      Results of these studies showed that while inclusion of 0.1 MUM HNE in the medium
      caused increased secretion of VEGF, its secretion and expression was
      significantly suppressed in the presence of >5 MUM HNE in the media. These
      concentration dependent hormetic effects of HNE on VEGF secretion could be
      blocked by the over expression of GSTA4-4 indicating that these effects were
      specifically attributed to HNE and regulated by GSTA4-4. VEGF secreted into the
      media showed angiogenic properties as indicated by increased migration and tube
      formation of HUVEC in matrigel when grown in media from RPE cells treated with 1
      MUM HNE. The corresponding media from GSTA4-4 over expressing RPE cells had no
      effect on migration and tube formation of HUVEC in matrigel. These results are
      consistent with earlier studies showing that at low concentrations, HNE promotes
      proliferative mechanisms and suggest that HNE induces VEGF secretion from RPE
      cells that acts in a paracrine fashion to induce angiogenic signaling mechanism
      in the endothelial cells. These findings may suggest a role of HNE and GSTA4-4 in
      oxidative stress induced proliferative retinopathies.

PMID- 22155254
TI  - Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by
      targeting c-myc.
AB  - Widespread functions of the c-myc pathway play a crucial role in renal cell
      carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto
      oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The
      levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were
      measured after transfecting the cells with let-7a mimics or a negative control.
      The change in c-myc protein level was confirmed by Western blot. The anti
      neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for
      proliferation analysis and cell flow cytometry for cell cycle analysis. The
      changes of downstream targets of c-myc were measured using reverse transcription
      quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that
      let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and
      c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1
      (CCND1) and the miR17-92 cluster, which is accompanied by proliferation
      inhibition and cell cycle arrest.

PMID- 22155255
TI  - CT-scan is a valuable tool to detect mandibular involvement in oral cancer
      patients.
AB  - In patients with oral squamous cell carcinomas (OSSC) it is desirable to avoid
      unnecessary bone resection without neglecting the overall surgical treatment goal
      of tumor-free margins. Whereas computed tomography (CT) is most commonly used to
      detect mandibular invasion, there are conflicting reports regarding the accuracy
      of CT. Therefore, the aim of this study was to reinvestigate the accuracy of CT
      in predicting mandibular involvement by OSSC. One hundred and seven patients with
      OSSC who received a mandibulectomy were included. Before treatment all patients
      underwent a contrast-enhanced multi-detector CT. Axial 3 or 1.25 mm thick images
      were reconstructed for evaluation in overlapping technique and displayed in a
      bone (1400/400 HU) and a soft tissue window (350/50 HU). CT scans were examined
      by three investigators and compared with the histological findings. The
      radiological examination showed a high interrater reliability (Cronbachs alpha
      0.982). Comparing the radiological findings with the histological results the CT
      showed 8 false-positive results and 8 false-negative patients. The quality
      criteria for detecting bone involvement of OSSC by CT were calculated as follows:
      sensitivity 82.6%; specificity 86.9%; positive predictive value 82.6%; negative
      predictive value 86.9%. However, in all false-positive patients a sagittal bone
      defect of 15.1mm could be found presumably caused by pressure of the tumor, but
      no histologically detectable bone infiltration. Modern CT (1-2 mm sections) is a
      valuable tool for surgical treatment planning. If bone invasion is detected, a
      mandibulectomy seems always reasonable. In radiologically negative cases
      histological assessment is necessary to detect mandibular involvement.

PMID- 22155256
TI  - Influence of irradiation and oncologic surgery on head and neck microsurgical
      reconstructions.
AB  - Despite the refinement of microsurgical techniques, microsurgical free flap
      transfer in patients with a history of previous radiotherapy, neck dissection or
      free flaps remains a challenge in oncologic reconstructive surgery. Previous
      studies on the prognostic factors for postoperative complications have been
      largely retrospective and shown conflicting results. Our aim was to design a
      prospective study to identify negative outcome predictors of free flap surgery in
      previously treated oral cancer patients. Prospective study including all patients
      who required microsurgical free flap transfer for reconstruction of the oral
      cavity between July of 2007 and June of 2010 with subset analysis of those cases
      in whom previous surgical or nonsurgical oncological treatment for head and neck
      cancer had been carried out. A total of 360 free flaps were performed in 358
      patients, of whom 61 had previous neck dissection and 58 had undergone radiation
      therapy. Operation time was significantly found to be longer in irradiated
      patients. The need for microsurgical revision, postoperative wound infection and
      free flap loss were significantly associated with the ASA score and a previous
      neck dissection. Wound infection was seen significantly more often after
      radiotherapy. Previous neck dissections and radiotherapy as well as the ASA score
      are significant negative predictors for success in free flap transfer. For
      patients with prior oncologic treatments in their medical history, we recommend
      detailed preoperative assessment of the vascular status and an intensified
      postoperative care to reduce complication rates to improve outcome in oncologic
      reconstructive surgery.

PMID- 22155257
TI  - The role of endocytosis on the uptake kinetics of luciferin-conjugated cell
      penetrating peptides.
AB  - Cell-penetrating peptides (CPPs) are short cationic/amphipathic peptides that can
      be used to deliver a variety of cargos into cells. However, it is still debated
      which routes CPPs employ to gain access to intracellular compartments. To assess
      this, most previously conducted studies have relied on information which is
      gained by using fluorescently labeled CPPs. More relevant information whether the
      internalized conjugates are biologically available has been gathered using end
      point assays with biological readouts. Uptake kinetic studies have shed even more
      light on the matter because the arbitrary choice of end-point might have profound
      effect how the results could be interpreted. To elucidate uptake mechanisms of
      CPPs, here we have used a bioluminescence based assay to measure cytosolic
      delivery kinetics of luciferin-CPP conjugates in the presence of endocytosis
      inhibitors. The results suggest that these conjugates are delivered into cytosol
      mainly via macropinocytosis; clathrin-mediated endocytosis and caveolae/lipid
      raft dependent endocytosis are involved in a smaller extent. Furthermore, we
      demonstrate how the involved endocytic routes and internalization kinetic
      profiles can depend on conjugate concentration in case of certain peptides, but
      not in case of others. The employed internalization route, however, likely
      dictates the intracellular fate and subsequent trafficking of internalized
      ligands, therefore emphasizing the importance of our novel findings for delivery
      vector development.

PMID- 22155258
TI  - Changes in membrane lipid composition cause alterations in epithelial cell-cell
      adhesion structures in renal papillary collecting duct cells.
AB  - In epithelial tissues, adherens junctions (AJ) mediate cell-cell adhesion by
      using proteins called E-cadherins, which span the plasma membrane, contact E
      cadherin on other cells and connect with the actin cytoskeleton inside the cell.
      Although AJ protein complexes are inserted in detergent-resistant membrane
      microdomains, the influence of membrane lipid composition in the preservation of
      AJ structures has not been extensively addressed. In the present work, we studied
      the contribution of membrane lipids to the preservation of renal epithelial cell
      cell adhesion structures. We biochemically characterized the lipid composition of
      membranes containing AJ complexes. By using lipid membrane-affecting agents, we
      found that such agents induced the formation of new AJ protein-containing domains
      of different lipid composition. By using both biochemical approaches and
      fluorescence microscopy we demonstrated that the membrane phospholipid
      composition plays an essential role in the in vivo maintenance of AJ structures
      involved in cell-cell adhesion structures in renal papillary collecting duct
      cells.

PMID- 22155259
TI  - What happens to personal identity when semantic knowledge degrades? A study of
      the self and autobiographical memory in semantic dementia.
AB  - While the self has been extensively explored in amnesic patients with severe
      episodic but not semantic memory disturbance, little is known about the self in
      semantic dementia (SD), which generally features the reverse pattern of
      impairment. In the present study, we investigated the structural (self
      representations) and functional (consciousness) dimensions of the self in a group
      of eight SD patients in the early to moderate stages of the disease. We used two
      original tasks designed to probe both structural characteristics, namely the
      strength and the certainty of self-concept and the episodic/semantic nature of
      self-representations, and functional characteristics, namely autonoetic/noetic
      level of consciousness, self-evaluation and self-projection into the past,
      present and future. Results for the structural self showed impairment on the
      semantic aspects of the self-representations, except for those related to the
      present. Moreover, SD patients were affected regardless of the episodic or
      semantic nature of self-representations into the future. As regards the
      functional self, self-projection and level of consciousness were only impaired
      for the future. This study confirms the persistence of a feeling of identity in
      SD over time for the past and present selves. However, it also highlights the
      loss of the future self in SD patients. These results are discussed in relation
      to models of long-term memory and future thinking focusing on the interplay of
      episodic and semantic memory and mental time travel.

PMID- 22155261
TI  - Nomogram for predicting 5-year disease-specific mortality after primary surgery
      for epithelial ovarian cancer.
AB  - OBJECTIVE: To develop a nomogram based on established prognostic factors to
      predict the probability of 5-year disease-specific mortality after primary
      surgery for patients with all stages of epithelial ovarian cancer (EOC) and
      compare the predictive accuracy with the currently used International Federation
      of Gynecology and Obstetrics (FIGO) staging system. METHODS: Using a
      prospectively kept database, we identified all patients with EOC who had their
      primary surgery at our institution between January 1996 and December 2004.
      Disease-specific mortality was estimated using the Kaplan-Meier method. Twenty
      eight clinical and pathologic factors were analyzed. Significant factors on
      univariate analysis were included in the Cox proportional hazards regression
      model, which identified factors utilized in the nomogram. The concordance index
      (CI) was used as an accuracy measure, with bootstrapping to correct for
      optimistic bias. Calibration plots were constructed. RESULTS: A total of 478
      patients with EOC were included. The most predictive nomogram was constructed
      using seven variables: age, FIGO stage, residual disease status, preoperative
      albumin level, histology, family history suggestive of hereditary breast/ovarian
      cancer (HBOC) syndrome, and American Society of Anesthesiologists (ASA) status.
      This nomogram was internally validated using bootstrapping and shown to have
      excellent calibration with a bootstrap-corrected CI of 0.714. The CI for FIGO
      staging alone was significantly less at 0.62 (P=0.002). CONCLUSION: We have
      developed an all-stage nomogram to predict 5-year disease-specific mortality
      after primary surgery for epithelial ovarian cancer. This tool is more accurate
      than FIGO staging and should be useful for patient counseling, clinical trial
      eligibility, postoperative management, and follow-up.

PMID- 22155260
TI  - The impact of novel retinoids in combination with platinum chemotherapy on
      ovarian cancer stem cells.
AB  - OBJECTIVE: Retinoids are important modulators of cell growth, differentiation,
      and proliferation. 9cUAB30, 9cUAB124, and 9cUAB130 are three novel retinoid
      compounds that show cytotoxic effects in other malignancies. We evaluated these
      novel retinoids in combination with chemotherapy against ovarian cancer stem
      cells (CSCs) in vitro and in an ex vivo model. METHODS: A2780 cells were plated
      in 96-well plates and treated with retinoid, carboplatin, or combination therapy.
      Cell viability was evaluated using ATPLite assay. The A2780 cell line was also
      analyzed for CSCs by evaluating ALDH activity using flow cytometry. A2780 cells
      treated ex vivo with retinoids and chemotherapy were injected into the flank of
      athymic nude mice in order to evaluate subsequent tumor initiating capacity.
      RESULTS: A2780 cells were sensitive to treatment with retinoids and carboplatin.
      The best treatment resulted from the combination of retinoid 9cUAB130 and
      carboplatin. Untreated A2780 cells demonstrated ALDH activity in 3.3% of the cell
      population. Carboplatin treatment enriched ALDH activity to 27.3%, while
      9cUAB130+/-carboplatin maintained the ALDH positive levels similar to untreated
      controls (2.3% and 6.7%, respectively). Similar results were found in tumorsphere
      forming conditions. Flank injections of ex vivo treated A2780 cells resulted in
      4/4 mice developing tumors at 40 days in the untreated group, while 0/4 tumors
      developed in the 9cUAB130 and carboplatin treated group. CONCLUSION: Combination
      treatment with carboplatin and retinoids reduced cell-viability, reduced CSC
      marker expression, and inhibited tumorigenicity, making it a more effective
      treatment when compared with carboplatin alone.

PMID- 22155262
TI  - A phase I study with an expanded cohort to assess the feasibility of intravenous
      paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in
      patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma:
      a Gynecologic Oncology Group study.
AB  - OBJECTIVE: To define the maximum tolerated dose (MTD) and assess the feasibility
      of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP
      paclitaxel in women with newly diagnosed Stages II-IV ovarian, fallopian tube, or
      primary peritoneal carcinoma. METHODS: Patients received escalating doses of
      paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60 mg/m(2) on day 8.
      A standard 3+3 design was used in the escalation phase. A two-stage group
      sequential design with 20 patients at the MTD was used in the feasibility phase.
      Patient-reported neurotoxicity was assessed pre and post treatment. RESULTS:
      Patients were treated with paclitaxel 175 mg/m(2) IV and carboplatin IP from AUC
      5-7 on day 1 and paclitaxel 60 mg/m(2) IP on day 8. The MTD was estimated at
      carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the
      first 4 cycles, seven (35%) of twenty evaluable patients had dose-limiting
      toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic
      fever (3), >2 week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3
      infection (1). De-escalation to paclitaxel 135 mg/m(2) IV was given to improve
      the safety. After six evaluable patients completed 4 cycles without a DLT,
      bevacizumab was added and six evaluable patients completed 4 cycles with one DLT
      (grade 3 hyponatremia). CONCLUSIONS: Paclitaxel at 175 mg/m(2) IV, carboplatin
      AUC 6 IP day 1 and paclitaxel 60 mg/m(2) IP day 8 yield 18-56% patients with
      DLTs. The tolerability of the regimen in combination with bevacizumab was
      indicated in a small cohort.

PMID- 22155263
TI  - Cellular localization and kinetic properties of Na(V)1.9-, Na(V)1.8-, and
      Na(V)1.7-like channel subtypes in Helix pomatia.
AB  - This article concerns the kinetics, selectivity, and distribution of the
      Na(V)1.9, Na(V)1.8, and Na(V)1.7 channel subtypes in the CNS of the snail, Helix
      pomatia. Within the snail brain, Na(V)1.9- and Na(V)1.8-like channel subtypes are
      widely expressed, with particularly high levels in the pedal, cerebral, and
      buccal ganglia. The suboesophageal ganglion contains equal amounts of neurons
      labeled with Na(V)1.9, 1.8, and 1.7 antibodies. Our data show that different
      types of ion channels are localized to discrete neurons and regions of the
      neuronal membrane affecting by this way the physiology of synaptic transmission
      or nerve conduction. Based on the voltage dependence and kinetics, the non- or
      slowly inactivating currents were observed in identified and nonidentified
      neurons of the snail CNS attributed to separate Na-channel subtypes. These
      observations provide the first evidence for the presence of the composite Na
      current in snail neurons. The significance of Na(V)1.9 channels in gastropod
      neurons is assigned to regulating the subthreshold membrane depolarization. First
      time, we have demonstrated that in addition to the Na(V)1.2-like channels most of
      the neurons contain Na(V)1.8- or 1.7-like channels carrying the composite inward
      sodium current. In this way, neurons containing different sets of channels
      differently are regulated, which allows further dynamic modulation of neuronal
      activity. The neuronal soma membrane revealed low ion selectivity of the Na
      channels with slow kinetics, which is a general property of gastropod molluscs.
      In addition, the relative similarity of the biophysical properties of voltage
      gated currents between vertebrates and invertebrates may reflect a structural
      similarity existing between Na-channel subtypes pointing to a common evolutionary
      origin.

PMID- 22155264
TI  - Distribution and function of polycystin-2 in mouse retinal ganglion cells.
AB  - The polycystin family of transient receptor potential (TRP) channels form Ca(2+)
      regulated cation channels with distinct subcellullar localizations and functions.
      As part of heteromultimeric channels and multi-protein complexes, polycystins
      control intracellular Ca(2+) signals and more generally the translation of
      extracellular signals and stimuli to intracellular responses. Polycystin-2
      channels have been cloned from retina, but their distribution and function in
      retinal ganglion cells (RGCs) have not yet been established. In the present
      study, we determined cellular and subcellular localization as well as functional
      properties of polycystin-2 channels in RGCs. Polycystin-2 expression and
      distribution in RGCs was assessed by immunohistochemistry on vertical cryostat
      section of mouse retina as well as primary cultured mouse RGCs, using
      fluorescence microscopy. Biophysical and pharmacological properties of polycystin
      2 channels isolated from primary cultured RGCs were determined using planar lipid
      bilayer electrophysiology. We detected polycystin-2 immunoreactivity both in the
      ganglion cell layer as well as in primary cultured RGCs. Subcellular analysis
      revealed strong cytosolic localization pattern of polycystin-2. Polycystin-2
      channel current was Ca(2+) activated, had a maximum slope conductance of 114 pS,
      and could be blocked in a dose-dependent manner by increasing concentrations of
      Mg(2+). The cytosolic localization of polycystin-2 in RGCs is in accordance with
      its function as intracellular Ca(2+) release channel. We conclude that polycystin
      2 forms functional channels in RGCs, of which biophysical and pharmacological
      properties are similar to polycystin-2 channels reported for other tissues and
      organisms. Our data suggest a potential role for polycystin-2 in RGC Ca(2+)
      signaling.

PMID- 22155266
TI  - Chronic caffeine consumption prevents cognitive decline from young to middle age
      in rats, and is associated with increased length, branching, and spine density of
      basal dendrites in CA1 hippocampal neurons.
AB  - Chronic caffeine consumption has been inversely associated with the risk of
      developing dementia and Alzheimer's disease. Here we assessed whether chronic
      caffeine treatment prevents the behavioral and cognitive decline that male Wistar
      rats experience from young (~3 months) to middle age (~10 months). When animals
      were young they were evaluated at weekly intervals in three tests: motor activity
      habituation in the open field (30-min sessions at the same time on consecutive
      days), continuous spontaneous alternation in the Y-maze (8 min), and elevated
      plus-maze (5 min). Afterward, rats from the same litter were randomly assigned
      either to a caffeine-treated group (n=13) or a control group (n=11), which
      received only tap water. Caffeine treatment (5 mg/kg/day) began when animals were
      ~4 months old, and lasted for 6 months. Behavioral tests were repeated from day
      14 to day 28 after caffeine withdrawal, a time period that is far in excess for
      the full excretion of a caffeine dose in this species. Thirty days after caffeine
      discontinuation brains were processed for Golgi-Cox staining. Compared with
      controls, we found that middle-aged rats that had chronically consumed low doses
      of caffeine (1) maintained their locomotor habituation during the second
      consecutive day exposure to the open field (an index of non-associative
      learning), (2) maintained their exploratory drive to complete the conventional
      minimum of nine arm visits required to calculate the alternation performance in
      the Y-maze in a greater proportion, (3) maintained their alternation percentage
      above chance level (an index of working memory), and (4) did not increase the
      anxiety indexes assessed by measuring the time spent in the open arms of the
      elevated plus maze. In addition, morphometric analysis of hippocampal neurons
      revealed that dendritic branching (90-140 MUm from the soma), length of 4th and
      5th order branches, total dendritic length, and spine density in distal dendritic
      branches were greater in the basal but not the apical dendrites of CA1 pyramidal
      neurons from rats chronically treated with caffeine, in comparison with their age
      and littermate-matched controls. Altogether, the present findings strengthen the
      epidemiological observations suggesting that prolonged caffeine intake prevents
      the cognitive decline associated with aging, and open the possibility that this
      process could be mediated by promoting the growth of dendrites and spines in
      neurons of the adult mammalian brain.

PMID- 22155265
TI  - Dim nighttime illumination alters photoperiodic responses of hamsters through the
      intergeniculate leaflet and other photic pathways.
AB  - In mammals, light entrains the central pacemaker within the suprachiasmatic
      nucleus (SCN) through both a direct neuronal projection from the retina and an
      indirect projection from the intergeniculate leaflet (IGL) of the thalamus.
      Although light comparable in intensity to moonlight is minimally effective at
      resetting the phase of the circadian clock, dimly lit and completely dark nights
      are nevertheless perceived differentially by the circadian system, even when
      nighttime illumination is below putative thresholds for phase resetting. Under a
      variety of experimental paradigms, dim nighttime illumination exerts effects that
      may be characterized as enhancing the plasticity of circadian entrainment. For
      example, relative to completely dark nights, dimly lit nights accelerate
      development of photoperiodic responses of Siberian hamsters transferred from
      summer to winter day lengths. Here we assess the neural pathways underlying this
      response by testing whether IGL lesions eliminate the effects of dim nighttime
      illumination under short day lengths. Consistent with previous work, dimly lit
      nights facilitated the expansion of activity duration under short day lengths.
      Ablation of the IGL, moreover, did not influence photoperiodic responses in
      animals held under completely dark nights. However, among animals that were
      provided dimly lit nights, IGL lesions prevented the short-day typical expansion
      of activity duration as well as the seasonally appropriate gonadal regression and
      reduction in body weight. Thus, the present data indicate that the IGL plays a
      central role in mediating the facilitative effects of dim nighttime illumination
      under short day lengths, but in the absence of the IGL, dim light at night
      influences photoperiodic responses through residual photic pathways.

PMID- 22155268
TI  - Assessment of the health impact of GM plant diets in long-term and
      multigenerational animal feeding trials: a literature review.
AB  - The aim of this systematic review was to collect data concerning the effects of
      diets containing GM maize, potato, soybean, rice, or triticale on animal health.
      We examined 12 long-term studies (of more than 90 days, up to 2 years in
      duration) and 12 multigenerational studies (from 2 to 5 generations). We
      referenced the 90-day studies on GM feed for which long-term or multigenerational
      study data were available. Many parameters have been examined using biochemical
      analyses, histological examination of specific organs, hematology and the
      detection of transgenic DNA. The statistical findings and methods have been
      considered from each study. Results from all the 24 studies do not suggest any
      health hazards and, in general, there were no statistically significant
      differences within parameters observed. However, some small differences were
      observed, though these fell within the normal variation range of the considered
      parameter and thus had no biological or toxicological significance. If required,
      a 90-day feeding study performed in rodents, according to the OECD Test
      Guideline, is generally considered sufficient in order to evaluate the health
      effects of GM feed. The studies reviewed present evidence to show that GM plants
      are nutritionally equivalent to their non-GM counterparts and can be safely used
      in food and feed.

PMID- 22155267
TI  - Novel stereoselective synthesis and chromatographic evaluation of E
      guggulsterone.
AB  - A new stereoselective synthesis of E-guggulsterone is described starting from
      androsten-3,17-dione. Protection of the ring A enonic system, followed by
      regioselective Wittig reaction and C-16 oxidation, affords E-guggulsterone in
      good yields and high stereoselectivity, making this approach easily accessible
      and scalable. Moreover, an original normal-phase HPLC method enabling the fast
      quantitation of the guggulsterone isomeric purity, combined with the suitability
      for sampling procedures, is detailed. The relying upon the cellulose-based
      Chiralpak IB column and the chloroform as the "non-standard" component of the
      eluent mixture, allows to get profitably high chromatographic performances.

PMID- 22155269
TI  - Occurrence of zearalenone, an oestrogenic mycotoxin, in Catalonia (Spain) and
      exposure assessment.
AB  - The objectives of this study were to assess the occurrence of zearalenone (ZEA)
      in food in Catalonia (Spain); to assess the consumption of the main food items
      contaminated with ZEA; and finally, to estimate the dietary exposure of the
      Catalonian population to the mycotoxin. Therefore 1187 samples were collected
      from the Catalonian market and pooled to obtain 485 analytical samples
      (composites) of the commodities most susceptible to ZEA contamination and
      commonly consumed in the region. Extraction and clean-up was performed using
      immunoaffinity columns and ZEA was detected and quantified by high performance
      liquid chromatography (HPLC) and fluorescence detection. A specific food
      frequency questionnaire (FFQ) was administered to 1264 individuals by trained
      interviewers to estimate the consumption of the relevant foods. The results
      showed that the occurrence of ZEA in food marketed in Catalonia was infrequent.
      Sliced bread, corn snacks and sweet corn were the commodities where it was most
      often present. In considering the contamination levels and food consumption
      estimates, the dietary intake of ZEA by the Catalonian population was estimated
      to be considerably lower than the temporary tolerable daily intake (TDI) of 200
      ng ZEA kg(-1) bw day(-1).

PMID- 22155270
TI  - Major furocoumarins in grapefruit juice II: phototoxicity, photogenotoxicity, and
      inhibitory potency vs. cytochrome P450 3A4 activity.
AB  - Furocoumarins are phototoxic and photogenotoxic natural constituents occurring in
      a broad variety of plants used in cosmetics, food, and drugs. Grapefruit juice is
      considered as a major dietary source of furocoumarins although very few is known
      about the phototoxic properties of furocoumarins in grapefruit. Here we analyzed
      the phototoxicity and photogenotoxicity of the three major furocoumarins
      previously found in commercial and freshly prepared grapefruit juices, i.e.
      bergaptol, bergamottin, and 6',7'-dihydroxy bergamottin (DHB). We found that DHB
      was much less toxic than the reference furocoumarin 5-methoxypsoralen (5-MOP) in
      V79 cells irradiated with UVA light, while bergamottin and bergaptol were not
      phototoxic. The photomutagenic potency, tested in the V79 HPRT mutagenicity
      assay, was found to be in the rank order 5-MOP>>DHB>bergamottin while bergaptol
      was not photomutagenic. In the V79 micronucleus assay, DHB was about 1/7 as
      potent as 5-MOP whereas bergaptol and bergamottin were inactive. In a cytochrome
      P450 3A4 inhibition assay in human liver microsomes, IC50 values of 1.2 MUM
      (DHB), 4.5 MUM (bergamottin), and 77.5 MUM (bergaptol) were found suggesting that
      all three furocoumarins contribute to the CYP3A4-inhibitory effect of grapefruit
      juice. These findings demonstrate that the sum of furocoumarins overestimates the
      phototoxic properties of grapefruit juice.

PMID- 22155271
TI  - Bioimpact of EGFR antagonists on the pilosebaceous follicles.
AB  - Cancer patients under targeted chemotherapy to the epidermal growth factor
      receptor (EGFR) frequently suffer from unusual skin adverse events. In the past,
      these changes were globally qualified as a rash. Our aim was to assess
      objectively by non invasive bioinstrumentation some early structural and
      functional skin changes associated with EGFR inhibitor treatment. A series of 27
      cancer patients aged 58-66 years were assessed using two ultraviolet light
      emitting CCD cameras, Visioscan((r)) and Visiopor((r)). Assessments were
      performed on the foreheads at inclusion and therefore at weekly intervals for 2
      months at most. No topical treatment was applied during the assessment period.
      The Visioscan((r)) camera revealed specular light reflectance at the site of
      follicular plugging. The interfollicular stratum corneum showed occasional focal
      hyperkeratosis. These features increased in severity with the EGFR inhibitor
      treatment, indicating follicular involvement as an early adverse event of the
      therapy. The follicular fluorescence revealed by the Visiopor((r)) camera
      remained unchanged over the treatment period. The present findings suggest an
      EGFR inhibitor-induced kerosis (follicular hyperkeratosis) possibly responsible
      for acneiform reactions.

PMID- 22155272
TI  - Bcl-XL, but not Bcl-2, can protect human B-lymphoma cell lines from parthenolide
      induced apoptosis.
AB  - In this report, we investigated the effects of the natural product parthenolide
      on human B-lymphoma cell lines. We show that parthenolide inhibited NF-kappaB
      transcription factor c-Rel (REL). In addition, the sensitivity of several human B
      lymphoma cell lines to parthenolide-induced apoptosis inversely correlated with
      their levels of anti-apoptosis protein Bcl-X(L). Furthermore, ectopic expression
      of Bcl-X(L) (but not Bcl-2) in two B-lymphoma cell lines decreased their
      sensitivity to parthenolide-induced apoptosis. Finally, over-expression of a
      transforming mutant of REL, which increased expression of endogenous Bcl-X(L),
      decreased the sensitivity of BJAB B-lymphoma cells to parthenolide-induced
      apoptosis. These results demonstrate that the NF-kappaB target gene products Bcl
      X(L) and Bcl-2 can play different roles in protecting B-lymphoma cells from
      chemical-induced apoptosis.

PMID- 22155274
TI  - Memory encoding and aging: a neurocognitive perspective.
AB  - This review article surveys the evidence for age-related changes in memory from
      cognitive and neuroimaging studies. It is probable that the observed declines in
      episodic memory with increasing age are a consequence of impairments in both
      acquisition (encoding) and retrieval - possibly for similar reasons - but the
      present review focuses on the former set of processes. An additional emphasis is
      on a processing approach to understanding age-related encoding deficiencies; we
      suggest that many problems stem from a decline in the ability to self-initiate
      deeper semantic processing operations. The article briefly discusses the role of
      declining sensory and perceptual abilities, but focuses primarily on the nature
      of processing resources, their consequences for memory acquisition, and on age
      related changes in cognition and neural functioning. We also survey the evidence
      for neuroplasticity in the older brain, and how compensatory activities at
      behavioral and neural levels can reduce age-related problems. Finally, we review
      recent studies of brain and cognitive training procedures. Age-related memory
      problems are real, but there are also grounds for optimism.

PMID- 22155273
TI  - Tuning shifts of the auditory system by corticocortical and corticofugal
      projections and conditioning.
AB  - The central auditory system consists of the lemniscal and nonlemniscal systems.
      The thalamic lemniscal and nonlemniscal auditory nuclei are different from each
      other in response properties and neural connectivities. The cortical auditory
      areas receiving the projections from these thalamic nuclei interact with each
      other through corticocortical projections and project down to the subcortical
      auditory nuclei. This corticofugal (descending) system forms multiple feedback
      loops with the ascending system. The corticocortical and corticofugal projections
      modulate auditory signal processing and play an essential role in the plasticity
      of the auditory system. Focal electric stimulation - comparable to repetitive
      tonal stimulation - of the lemniscal system evokes three major types of changes
      in the physiological properties, such as the tuning to specific values of
      acoustic parameters of cortical and subcortical auditory neurons through
      different combinations of facilitation and inhibition. For such changes, a
      neuromodulator, acetylcholine, plays an essential role. Electric stimulation of
      the nonlemniscal system evokes changes in the lemniscal system that is different
      from those evoked by the lemniscal stimulation. Auditory signals ascending from
      the lemniscal and nonlemniscal thalamic nuclei to the cortical auditory areas
      appear to be selected or adjusted by a "differential" gating mechanism.
      Conditioning for associative learning and pseudo-conditioning for nonassociative
      learning respectively elicit tone-specific and nonspecific plastic changes. The
      lemniscal, corticofugal and cholinergic systems are involved in eliciting the
      former, but not the latter. The current article reviews the recent progress in
      the research of corticocortical and corticofugal modulations of the auditory
      system and its plasticity elicited by conditioning and pseudo-conditioning.

PMID- 22155275
TI  - Redox, mutagenic and structural studies of the glutaredoxin/arsenate reductase
      couple from the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The arsenate reductase from the cyanobacterium Synechocystis sp. PCC 6803 has
      been characterized in terms of the redox properties of its cysteine residues and
      their role in the reaction catalyzed by the enzyme. Of the five cysteines present
      in the enzyme, two (Cys13 and Cys35) have been shown not to be required for
      catalysis, while Cys8, Cys80 and Cys82 have been shown to be essential. The as
      isolated enzyme contains a single disulfide, formed between Cys80 and Cys82, with
      an oxidation-reduction midpoint potential (E(m)) value of -165mV at pH 7.0. It
      has been shown that Cys15 is the only one of the four cysteines present in
      Synechocystis sp. PCC 6803 glutaredoxin A required for its ability to serve as an
      electron donor to arsenate reductase, while the other three cysteines (Cys18,
      Cys36 and Cys70) play no role. Glutaredoxin A has been shown to contain a single
      redox-active disulfide/dithiol couple, with a two-electron, E(m) value of -220mV
      at pH 7.0. One cysteine in this disulfide/dithiol couple has been shown to
      undergo glutathionylation. An X-ray crystal structure, at 1.8A resolution, has
      been obtained for glutaredoxin A. The probable orientations of arsenate reductase
      disulfide bonds present in the resting enzyme and in a likely reaction
      intermediate of the enzyme have been examined by in silico modeling, as has the
      surface environment of arsenate reductase in the vicinity of Cys8, the likely
      site for the initial reaction between arsenate and the enzyme.

PMID- 22155276
TI  - Relationship between stability and flexibility in the most flexible region of
      Photinus pyralis luciferase.
AB  - Firefly luciferase is a protein with a large N-terminal and a small C-terminal
      domain. B-factor analysis shows that its C-terminal is much more flexible than
      its N-terminal. Studies on hyperthermophile proteins have been shown that the
      increased thermal stability of hyperthermophile proteins is due to their enhanced
      conformational rigidity and the relationship between flexibility, stability and
      function in most of proteins is on debate. Two mutations (D474K and D476N) in the
      most flexible region of firefly luciferase were designed. Thermostability
      analysis shows that D476N mutation doesn't have any significant effect but D474K
      mutation destabilized protein. On the other hand, flexibility analysis using
      dynamic quenching and limited proteolysis demonstrates that D474K mutation became
      much more flexible than wild type although D476N doesn't have any significant
      difference. Intrinsic and ANS fluorescence studies demonstrate that D476N
      mutation is brought about by structural changes without significant effect on
      thermostability and flexibility. Molecular modeling reveals that disruption of a
      salt bridge between D(474) and K(445) accompanying with some H-bond deletion may
      be involved in destabilization of D474K mutant.

PMID- 22155277
TI  - Sources of high PM2.5 concentrations in Milan, Northern Italy: molecular marker
      data and CMB modelling.
AB  - In Milan (MI), the largest city in Northern Italy, the annually average PM2.5
      concentration is above 25 MUg m(-3), the value that the EU established as a
      target for 2010, and the upper limit from 2015 onwards (2008/30/CE). Over a three
      year period (2006-2009) PM concentrations and chemical compositions were measured
      in an urban site (MI), a rural site (OB) and a remote site (ASC) in Northern
      Italy. Chemical characterization (EC/OC, inorganic ions, elements, C20-C32 n
      alkanes, C2-C5 mono and dicarboxylic acids, levoglucosan and PAHs) was carried
      out on PM2.5 samples from the three sites, and PM10 from MI. Molecular markers
      were used in Chemical Mass Balance (CMB) modelling to estimate the contributions
      of primary sources to OC, and then PM mass from each source was reconstructed in
      MI, OB and ASC for different seasons. Estimates of the traffic (TR) source
      contribution to PM2.5 mass ranged from 4.1 (+/- 2.0) MUg m(-3) during the summer,
      to 13.3 (+/- 6.7) MUg m(-3) during the winter in MI. TR was the main primary
      source for PM2.5 concentrations in MI (17-24%). Its contribution was lower at the
      OB site (7-9%) and at the remote ASC site (3-4%). TR is a local source, while
      biomass burning (BB) is a diffuse regional source in Northern Italy: during fall
      and winter, BB was 25-30% and 27-31% of PM2.5 at MI and OB respectively. Other
      primary sources accounted for a small amount of the PM2.5, i.e. natural gas
      combustion (0-1%), plant debris (0-4%), road dust (RD=0-4%; but 15% at ASC during
      winter and 10% of PM10 at MI during summer) and sea salt (0-1%). Secondary
      inorganic+organic aerosol constituted the major part of the PM2.5 mass during
      spring and summer (50-65%) at the three sites.

PMID- 22155278
TI  - Isolation and characterization of cDNAs encoding Ars2 and Pasha homologues, two
      components of the RNA interference pathway in Litopenaeus vannamei.
AB  - The RNA interference (RNAi) is an evolutionarily conserved protective mechanism
      in eukaryotes against parasitic foreign nucleic acids. Previous studies
      demonstrated that the RNAi mechanism is important for shrimp antiviral immunity.
      Here, we report the identification and functional analysis of two key components
      of the shrimp RNAi activity: Litopenaeus vannamei arsenite resistance gene 2
      (LvArs2) and partner of drosha (LvPasha). The full-length cDNA of LvArs2 was 3470
      bp, including a 5' untranslated region (UTR) of 167 bp, a 3' UTR of 639 bp, and
      an open reading frame (ORF) of 2664 bp that encoded 887 amino acid residues with
      an estimated molecular mass of 102.5 kDa. The full-length cDNA of LvPasha was
      2654 bp, including a 5' UTR of 99 bp, a 3' UTR of 560 bp, and an ORF of 1995 bp
      that encoded 664 amino acid residues with an estimated molecular mass of 74.2
      kDa. Co-immunoprecipitation demonstrated that LvArs2 interacted with L. vannamei
      Dicer2 (LvDcr2) and LvPasha in Drosophila Schneider 2 (S2) cells, suggesting that
      LvArs2 may be involved in regulation of the miRNA/siRNA pathways in L.vannamei.
      Subcellular localization assays demonstrated both LvArs2 and LvPasha proteins
      mainly presented in the nucleus. After Poly(C-G) stimulation, the expression of
      LvArs2 was suppressed and expression of LvPasha was enhanced in shrimp gills.
      These results suggest that LvArs2 and LvPasha may participate in the defense
      against RNA viruses in crustacea.

PMID- 22155279
TI  - Molecular cloning and comprehensive characterization of cathepsin D in the Miiuy
      croaker Miichthys miiuy.

PMID- 22155280
TI  - A novel putative lipoprotein receptor (CasLpR) in the hemocytes of the blue crab,
      Callinectes sapidus: cloning and up-regulated expression after the injection of
      LPS and LTA.
AB  - The full-length cDNA encoding a putative lipoprotein receptor (CasLpR) was
      isolated from the hemocytes of Callinectes sapidus using 5' and 3' RACEs. The
      open reading frame for CasLpR contains a precursor of putative CasLpR consisting
      of 1710 amino acid residues including 22 amino acid residues of the signal
      peptide (22 amino acids). Mature CasLpR (1688 amino acids with 5.6% of
      phosphorylation sites) has multiple, putative functional domains: five low
      density lipoprotein receptor domains in the N-terminus, and a G-protein-coupled
      receptor proteolysis site domain and a 7 transmembrane receptor (secretin family)
      domain in the C-terminus. To date, there are no proteins with a similar domain
      structure in the GenBank. The expression pattern of CasLpR was exclusive in
      hemocytes among all tested tissues obtained from a juvenile female at intermolt
      stage: brain, eyestalk ganglia, pericardial organs, and thoracic ganglia complex
      (nervous system); hepatopancreas (digestive system); heart, artery and hemocytes
      (circulatory system); gill and antennal gland (excretory system), hypodermis; and
      Y-organ (endocrine organ). There was no CasLpR expression in the ovary of an
      adult female. A putative function of CasLpR was examined after challenges of
      lipopolysaccharides (LPS) and lipoteichoic acid (LTA) in vivo using qRT-PCR
      assays. Animals at 24 h after injection of LPS or LTA up-regulated the expression
      of CasLpR in hemocytes by ~3.5 and 1.4 folds, respectively, compared to the
      controls that received saline injection. LPS challenge also caused the greatest
      increment (~55 folds) of heat shock protein 90 (Hsp90) expression in these
      samples. These data indicate that putative CasLpR and CasHsp90 may be involved in
      the defense system or the stress response of C. sapidus.

PMID- 22155281
TI  - Do hummingbirds have a sweet-tooth? Gustatory sugar thresholds and sugar
      selection in the broad-billed hummingbird Cynanthus latirostris.
AB  - Nectar is a solution of mainly three sugars: sucrose, glucose and fructose.
      Studies have demonstrated that pollinators have preferences according to the
      sugar composition presented in their diet, and these preferences may be caused by
      sugar assimilation capacities. However, sugar flavor could also play an important
      role for sugar preferences of nectar-feeding animals. We evaluated the sugar
      gustatory thresholds of the broad-billed hummingbird Cynanthus latirostris for
      sucrose, glucose, fructose and a 1:1 mixture of glucose-fructose. We presented
      eight C. latirostris to paired feeders containing either a sugar solution or pure
      water. Additionally, we conducted sugar preference tests at three different
      concentrations (146, 730 and 1022mmolL(-1)), to relate sugar preferences with
      sugar gustatory thresholds. C. latirostris had different gustatory thresholds for
      the three different sugars tested. At low sugar concentrations (146mmolL(-1)),
      sugar selection followed the gustatory thresholds. Hummingbird sugar preference
      patterns can be affected by different mechanisms, both pre- and post-ingestive.
      At low concentrations gustatory thresholds may play an important role to
      determine sugar selection. However, at intermediate and high concentrations,
      sugar assimilation rates, and velocity of food processing generated by osmotic
      constraints, can be the mechanisms that explain the sugar selection of these
      animals.

PMID- 22155282
TI  - Increased brain metabolism after acute administration of the synthetic
      cannabinoid HU210: a small animal PET imaging study with 18F-FDG.
AB  - Cannabis use has been shown to alter brain metabolism in both rat models and
      humans although the observations between both species are conflicting. In the
      present study, we examined the short term effects of a single-dose injection of
      the synthetic cannabinoid agonist HU210 on glucose metabolism in the rat brain
      using small animal (18)F-2-fluoro-deoxyglucose (FDG) Positron Emission Tomography
      (PET) 15 min (Day 1) and 24h (Day 2) post-injection of the agonist in the same
      animal. Young adult male Wistar rats received an intra-peritoneal injection of
      HU210 (100 MUg/kg, n=7) or vehicle (n=5) on Day 1. Approximately 1mCi of (18)F
      FDG was injected intravenously into each animal at 15 min (Day 1) and 24h (Day 2)
      post-injection of HU210. A 5-min Computer Tomography (CT) scan followed by a 20
      min PET scan was performed 40 min after each (18)F-FDG injection. Standardised
      Uptake Values (SUVs) were calculated for 10 brain regions of interest (ROIs).
      Global increased SUVs in the whole brain, hence global brain metabolism, were
      observed following HU210 treatment on Day 1 compared to the controls (21%,
      P<0.0001), but not in individual brain regions. On Day 2, however, no
      statistically significant differences were observed between the treated and
      control groups. At the 24h time point (Day 2), SUVs in the HU210 treated group
      returned to control levels (21-30% decrease compared to Day 1), in all ROIs
      investigated (P<0.0001). In the control group, SUVs did not differ between the
      two acquisition days in all brain regions. The present results suggest that high
      dose HU210 increases brain glucose metabolism in the rat brain shortly after
      administration, in line with normalised human in vivo studies, an effect that was
      no longer apparent 24 h later.

PMID- 22155283
TI  - Agmatine in the brain: an emerging "human" perspective.

PMID- 22155284
TI  - Auditory processing in autism spectrum disorder: a review.
AB  - For individuals with autism spectrum disorder or 'ASD' the ability to accurately
      process and interpret auditory information is often difficult. Here we review
      behavioural, neurophysiological and imaging literature pertaining to this field
      with the aim of providing a comprehensive account of auditory processing in ASD,
      and thus an effective tool to aid further research. Literature was sourced from
      peer-reviewed journals published over the last two decades which best represent
      research conducted in these areas. Findings show substantial evidence for
      atypical processing of auditory information in ASD at behavioural and neural
      levels. Abnormalities are diverse, ranging from atypical perception of various
      low-level perceptual features (i.e. pitch, loudness) to processing of more
      complex auditory information such as prosody. Trends across studies suggest
      auditory processing impairments in ASD are most likely to present during
      processing of complex auditory information and are more severe for speech than
      for non-speech stimuli. The interpretation of these findings with respect to
      various cognitive accounts of ASD is discussed and suggestions offered for
      further research.

PMID- 22155285
TI  - Dynamics of arachidonic acid mobilization by inflammatory cells.
AB  - The development of mass spectrometry-based techniques is opening new insights
      into the understanding of arachidonic acid (AA) metabolism. AA incorporation,
      remodeling and release are collectively controlled by acyltransferases,
      phospholipases and transacylases that exquisitely regulate the distribution of AA
      between the different glycerophospholipid species and its mobilization during
      cellular stimulation. Traditionally, studies involving phospholipid AA metabolism
      were conducted by using radioactive precursors and scintillation counting from
      thin layer chromatography separations that provided only information about lipid
      classes. Today, the input of lipidomic approaches offers the possibility of
      characterizing and quantifying specific molecular species with great accuracy and
      within a biological context associated to protein and/or gene expression in a
      temporal frame. This review summarizes recent results applying mass spectrometry
      based lipidomic approaches to the identification of AA-containing
      glycerophospholipids, phospholipid AA remodeling and synthesis of oxygenated
      metabolites.

PMID- 22155286
TI  - "Performance qualification of a new hypromellose capsule. Part I. Comparative
      evaluation of physical, mechanical and processability quality attributes of Vcaps
      Plus, Quali-V and gelatin capsules and Part II. Disintegration and dissolution
      comparison between two types of hypromellose capsules" by M. Sherry Ku et al.

PMID- 22155287
TI  - Stabilization of tetanus toxoid formulation containing aluminium hydroxide
      adjuvant against agitation.
AB  - The aggregation of tetanus toxoid leads to reduced bioavailability of the vaccine
      and failure of immunization programmes in many parts of the globe. One of the
      main reasons for denaturation and aggregation of tetanus toxoid formulations is
      agitation of the protein during transport. We have identified that agitation
      leads to collapse of the gel matrix of aluminium hydroxide which is used as an
      adjuvant in these preparations. This results in desorption of the toxoid from the
      matrix, which then loses its antigenicity due to agitation-induced denaturation
      of the protein. We show that incorporation of some compatible osmolytes like
      sorbitol, glucose and arginine, but not trehalose, is able to protect the
      adjuvant matrix from degradation, and retain the integrity of the vaccine
      preparation in terms of its antigenicity.

PMID- 22155288
TI  - Correlation of the amino-acid sequence and the 3D structure of the functional
      domain of EmaA from Aggregatibacter actinomycetemcomitans.
AB  - Adhesion to collagen is an important virulence determinant for the periodontal
      pathogen Aggregatibacter actinomycetemcomitans. Binding to collagen is mediated
      by the extracellular-matrix protein adhesin-A (EmaA). EmaA is a homotrimeric
      autotransporter protein that forms flexible antenna-like appendages on the
      bacterium surface. An ellipsoidal structure at the distal end of the appendage,
      composed of three subdomains, contains the functional domain of the molecule. A
      correlation between amino-acid sequence and subdomain structure (SI and SII) was
      proposed based on an analysis of the volume/molecular weight ratio. EmaA from
      three mutant strains (deletions of amino-acids 70-206 and 70-386 and a
      substitution mutation G162S) has been studied by electron microscopy to test this
      hypothesis. 3D structures were analyzed using single-axis tilt tomography of
      negatively stained preparations of bacteria combined with subvolume averaging.
      Additionally, a large number of 2D images of the apical domain of the adhesins
      from the mutants were extracted from micrographs of the bacterial surface,
      aligned and classified. The combined data showed that amino-acids 70-206 localize
      to subdomain SI and 70-386 comprise subdomains SI and SII. Moreover, we showed
      that the substitution mutation G162S, which abolishes collagen binding activity,
      does not affect the overall structural integrity of the functional domain.
      However, the structure of subdomain SI in this mutant is slightly altered with
      respect to the wild-type strain. These data also have allowed us to interpret the
      architectural features of each subdomain of EmaA in more detail and to correlate
      the 3D structure of the functional domain of EmaA with the amino-acid sequence.

PMID- 22155289
TI  - Automatic alignment and reconstruction of images for soft X-ray tomography.
AB  - Soft X-ray tomography (SXT) is a powerful imaging technique that generates
      quantitative, 3D images of the structural organization of whole cells in a near
      native state. SXT is also a high-throughput imaging technique. At the National
      Center for X-ray Tomography (NCXT), specimen preparation and image collection for
      tomographic reconstruction of a whole cell require only minutes. Aligning and
      reconstructing the data, however, take significantly longer. Here we describe a
      new component of the high throughput computational pipeline used for processing
      data at the NCXT. We have developed a new method for automatic alignment of
      projection images that does not require fiducial markers or manual interaction
      with the software. This method has been optimized for SXT data sets, which
      routinely involve full rotation of the specimen. This software gives users of the
      NCXT SXT instrument a new capability - virtually real-time initial 3D results
      during an imaging experiment, which can later be further refined. The new code,
      Automatic Reconstruction 3D (AREC3D), is also fast, reliable, and robust. The
      fundamental architecture of the code is also adaptable to high performance GPU
      processing, which enables significant improvements in speed and fidelity.

PMID- 22155290
TI  - Crystal structures of salicylate 1,2-dioxygenase-substrates adducts: A step
      towards the comprehension of the structural basis for substrate selection in
      class III ring cleaving dioxygenases.
AB  - The crystallographic structures of the adducts of salicylate 1,2-dioxygenase
      (SDO) with substrates salicylate, gentisate and 1-hydroxy-2-naphthoate, obtained
      under anaerobic conditions, have been solved and analyzed. This ring fission
      dioxygenase from the naphthalenesulfonate-degrading bacterium Pseudaminobacter
      salicylatoxidans BN12, is a homo-tetrameric class III ring-cleaving dioxygenase
      containing a catalytic Fe(II) ion coordinated by three histidine residues. SDO is
      markedly different from the known gentisate 1,2-dioxygenases or 1-hydroxy-2
      naphthoate dioxygenases, belonging to the same class, because of its unique
      ability to oxidatively cleave salicylate, gentisate and 1-hydroxy-2-naphthoate.
      The crystal structures of the anaerobic complexes of the SDO reveal the mode of
      binding of the substrates into the active site and unveil the residues which are
      important for the correct positioning of the substrate molecules. Upon binding of
      the substrates the active site of SDO undergoes a series of conformational
      changes: in particular Arg127, His162, and Arg83 move to make hydrogen bond
      interactions with the carboxyl group of the substrate molecules. Unpredicted
      concerted displacements upon substrate binding are observed for the loops
      composed of residues 40-43, 75-85, and 192-198 where several aminoacidic
      residues, such as Leu42, Arg79, Arg83, and Asp194, contribute to the closing of
      the active site together with the amino-terminal tail (residues 2-15).
      Differences in substrate specificity are controlled by several residues located
      in the upper part of the substrate binding cavity like Met46, Ala85, Trp104, and
      Phe189, although we cannot exclude that the kinetic differences observed could
      also be generated by concerted conformational changes resulting from amino-acid
      mutations far from the active site.

PMID- 22155291
TI  - Towards an atlas of mammalian cell ultrastructure by cryo soft X-ray tomography.
AB  - We provide a catalog of 3D cryo soft X-ray tomography (cryo-SXT) images obtained
      from ~6 to 12MUm thick mouse adenocarcinoma cells. Included are multiple
      representative images of nuclei, nucleoli, nuclear membrane, nuclear membrane
      channels, mitochondria, lysosomes, endoplasmic reticulum, filaments and plasma
      membrane, plus three structures not previously described by cryo-SXT, namely
      Golgi, microvilli and nuclear-membrane blebs. Sections from the 3D cryo-SXT
      tomograms for all the preceding structures closely resemble those seen by thin
      section transmission electron microscopy (TEM). Some structures such as nuclear
      membrane channels and nuclear-membrane blebs are more easily detected by cryo-SXT
      than TEM most likely due to their better contrast and cellular preservation in
      cryo-SXT combined with the ability to rapidly locate these structures within a
      full 3D image. We identify and discuss two current limitations in cryo-SXT:
      variability in image quality and difficulties in detecting weaker contrast
      structures such as chromatin and various nuclear bodies. Progress on these points
      is likely to come from the solution of several technical problems in image
      acquisition, plus the implementation of advanced cryo soft X-ray microscopy
      approaches such as phase contrast or optical sectioning.

PMID- 22155292
TI  - Bone marrow-derived cells do not engraft into skeletal muscle microvasculature
      but promote angiogenesis after acute injury.
AB  - The skeletal muscle is supported by a vast network of microvessels with the
      capacity to regenerate in response to injury. However, the dynamics of
      microvascular repair and the origin of reconstituted endothelial cells in the
      skeletal muscle are poorly understood. A growing body of literature exists to
      indicate bone marrow (BM)-derived cells engraft into regenerating vascular
      endothelium and muscle macrovasculature. Therefore, we investigated the extent of
      BM contribution to skeletal muscle microvasculature after acute injury. Because
      reporters and markers commonly used to trace donor BM cells are not endothelial
      specific but are also expressed by leukocytes, we generated novel BM chimeras
      utilizing Tie2-green fluorescent protein BM cells transplanted into CD31 and
      Caveolin-1 knockout recipients. In turn, we surveyed BM vascular contribution,
      not just by the presence of green fluorescent protein, but also CD31 and Caveolin
      1, respectively. After stable BM reconstitution, chimera limb muscles were
      cardiotoxin (CTX) injured and examined 21 days post-injury for the presence of
      green fluorescent protein, CD31, and Caveolin-1. Acute muscle injury by CTX is
      characterized by initial microvasculature death followed by rapid endothelial
      regeneration within 14 days post-damage. Histological analysis of injured and
      uninjured contralateral limb muscles revealed a complete absence of BM
      engraftment in the muscle vasculature of wild-type and CD31/Caveolin-1 knockout
      chimeras. In contrast, F4/80(+) cells isolated from CTX-injured muscle, expressed
      endothelial-related markers and promoted angiogenesis in vitro. Therefore,
      despite the absence of BM engraftment to regenerated skeletal muscle
      microvasculature, macrophages recruited after injury promote angiogenesis and, in
      turn, vascular regeneration.

PMID- 22155293
TI  - Estimation of the rate and effect of new beneficial mutations in asexual
      populations.
AB  - The rate and effect of available beneficial mutations are key parameters in
      determining how a population adapts to a new environment. However, these
      parameters are poorly known, in large part because of the difficulty of designing
      and interpreting experiments to examine the rare and intrinsically stochastic
      process of mutation occurrence. We present a new approach to estimate the rate
      and selective advantage of beneficial mutations that underlie the adaptation of
      asexual populations. We base our approach on the analysis of experiments that
      track the effect of newly arising beneficial mutations on the dynamics of a
      neutral marker in evolving bacterial populations and develop efficient estimators
      of mutation rate and selective advantage. Using extensive simulations, we
      evaluate the accuracy of our estimators and conclude that they are quite robust
      to the use of relatively low experimental replication. To validate the
      predictions of our model, we compare theoretical and experimentally determined
      estimates of the selective advantage of the first beneficial mutation to fix in a
      series of ten replicate populations. We find that our theoretical predictions are
      not significantly different from experimentally determined selection
      coefficients. Application of our method to suitably designed experiments will
      allow estimation of how population evolvability depends on demographic and
      initial fitness parameters.

PMID- 22155294
TI  - Protein kinase domain of CTR1 from Arabidopsis thaliana promotes ethylene
      receptor cross talk.
AB  - Ethylene controls many aspects of plant growth and development. Signaling by the
      gaseous phytohormone is initiated by disulfide-linked membrane-bound receptors,
      and the formation of heteromeric receptor clusters contributes to the broad range
      of ethylene responsiveness. In Arabidopsis thaliana, the TCS-like ethylene
      receptors interact with the cytosolic serine/threonine kinase constitutive triple
      response 1 (CTR1), a proposed mitogen-activated protein kinase kinase kinase. In
      the absence of the hormone, the receptor and therefore CTR1 are active. Hence,
      ethylene acts as an inverse agonist of its signaling pathway. The three
      dimensional structures of the active, triphosphorylated and the unphosphorylated,
      inactive kinase domain of CTR1 in complex with staurosporine illustrate the
      conformational rearrangements that form the basis of activity regulation.
      Additionally, in analytical ultracentrifugation experiments, active kinase
      domains form back-to-back dimers, while inactive and activation loop variants are
      monomers. Together with a front-to-front activation interface, the active protein
      kinase dimers thereby engage in interactions that promote CTR1-mediated cross
      talk between ethylene receptor clusters. This model provides a structural
      foundation for the observed high sensitivity of plants to ethylene.

PMID- 22155295
TI  - Drug resistance in cancer. Editorial.

PMID- 22155296
TI  - Electroacupuncture inhibits phosphorylation of spinal phosphatidylinositol 3
      kinase/Akt in a carrageenan-induced inflammatory rat model.
AB  - We investigated the changes of pain-related spinal signaling pathway after
      electroacupuncture (EA) stimulation in a carrageenan-induced rat model. EA
      stimulation (2Hz, 1mA) was needle-delivered for 30 min at acupoints corresponding
      to Zusanli and Sanyinjiao 3 h after carrageenan injection. Thermal and mechanical
      sensitivity of the hindpaw induced by carrageenan was strongly inhibited by EA
      stimulation. Phosphorylation of extracellular signal-regulated kinase,
      phosphatidylinositol 3-kinase (PI3K), Akt, and cAMP response element-binding
      protein (CREB) were examined in the L4-5 segments of the spinal cord by Western
      blot analysis 4h and 5h after carrageenan injection. Phosphorylation of Akt and
      especially PI3K were significantly induced by carrageenan-induction, but these
      expressions were markedly inhibited by EA stimulation. CREB phosphorylation
      showed a similar, but insignificant, pattern as like PI3k/Akt.
      Immunohistochemical analyses confirmed that phosphorylation of PI3K and Akt
      showed a similar pattern as Western blotting and were observed in most neurons
      and a few astrocytes. EA and PI3K inhibitor synergistically inhibited carrageenan
      induced hyperalgesia. These results reveal that both neuronal PI3K and Akt may
      play an important role in EA-induced antinociception via inactivation in an
      inflammatory pain model.

PMID- 22155297
TI  - Antioxidant properties of natural polyphenols and their therapeutic potentials
      for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and most
      common cause of dementia. However, there is no known way to halt or cure the
      neurodegenerative disease. Oxidative stress is a cardinal hallmark of the disease
      and has been considered as therapeutic target for AD treatment. Several factors
      may contribute to oxidative stress in AD brains. First, mitochondrion is a key
      player that produces reactive oxygen species (ROS). Mitochondrial dysfunction
      found in AD patients may exaggerate generation of ROS and oxidative stress.
      Second, amyloid-beta peptide generates ROS in the presence of metal ions such as
      Fe(2+) and Cu(2+). Third, activated glial cells in AD brains may produce
      excessive amount of superoxide and nitric oxide through NADPH oxidase and
      inducible nitric oxide synthase, respectively. Increased ROS can cause damage to
      protein, lipid and nucleic acids. Numerous studies demonstrated that natural
      polyphenolic compounds protect against various neurotoxic insults in vitro and in
      vivo AD models. In these studies, dietary polyphenolic compounds exhibit
      neuroprotective effects through scavenging free radicals and increasing
      antioxidant capacity. Furthermore, they could facilitate the endogenous
      antioxidant system by stimulating transcription. Some epidemiological and
      clinical studies highlighted their therapeutic potential for AD treatment. In
      this review, we will briefly discuss causes of oxidative stress in AD brains, and
      describe antioxidant neuroprotective effects and therapeutic potential for AD of
      selected natural polyphenolic compounds.

PMID- 22155298
TI  - Angioedema: patients experience and treatment relief.
AB  - Angioedema is defined as a swelling of the skin, mucosa and submucosa of the
      respiratory tract. It may also impair the intestinal epithelium and other mucous
      membranes. It can be potentially life-threatening if the upper respiratory tract
      is involved. In these cases emergency treatment is often required in particular
      if the pharynx and larynx are swollen. Beside the well-known etiologies of
      allergic angioedema, many forms of nonallergic angioedema are known and in the
      majority of these forms increased plasma and tissue concentrations of bradykinin
      play a critical role.

PMID- 22155299
TI  - Rationale for plasma exchange turns to innate immunity.

PMID- 22155300
TI  - NCAM2/OCAM/RNCAM: cell adhesion molecule with a role in neuronal
      compartmentalization.
AB  - Neural cell adhesion molecules 2 (NCAM2/OCAM/RNCAM), is a paralog of NCAM1. The
      protein exists in a transmembrane and a lipid-anchored isoform, and has an
      ectodomain consisting of five immunoglobulin modules and two fibronectin type 3
      homology modules. Structural models of the NCAM2 ectodomain reveal that it
      facilitates cell adhesion through reciprocal interactions between the membrane
      distal immunoglobulin modules. There are no known heterophilic NCAM2 binding
      partners, and NCAM2 is not glycosylated with polysialic acid, a posttranslational
      modification known to be a major modulator of NCAM1-mediated processes. This
      suggests that NCAM2 has a function or mode of action distinctly different from
      that of NCAM1. NCAM2 is primarily expressed in the brain, where it is believed to
      stimulate neurite outgrowth and to facilitate dendritic and axonal
      compartmentalization.

PMID- 22155301
TI  - Angiotensin signalling in pulmonary fibrosis.
AB  - A large body of evidence demonstrates that angiotensin II and angiotensin
      receptors are required for the pathogenesis of experimental lung fibrosis.
      Angiotensin has a number of profibrotic effects on lung parenchymal cells that
      include the induction of growth factors for mesenchymal cells, extracellular
      matrix molecules, cytokines and increased motility of lung fibroblasts.
      Angiotensin is also proapoptotic for lung epithelial cells, and is synthesized by
      a local system (i.e., entirely within the lung tissue) after lung injury by a
      variety of agents of both xenobiotic and endogenous origins. Recent evidence
      shows that the counterregulatory molecule angiotensin 1-7, the product of the
      enzyme ACE-2, inhibits epithelial cell apoptosis and thus acts as an antifibrotic
      epithelial survival factor. This manuscript reviews the evidence supporting a
      role for angiotensin in lung fibrogenesis and discusses the signalling mechanisms
      underlying its action on lung parenchymal cells important in the pathogenesis of
      pulmonary fibrosis.

PMID- 22155302
TI  - Withanone binds to mortalin and abrogates mortalin-p53 complex: computational and
      experimental evidence.
AB  - Mortalin binds to p53 tumor suppressor protein and sequesters it in the
      cytoplasm. This results in an inhibition of the transcriptional activation and
      control of centrosome duplication functions of p53, thus contributing to human
      carcinogenesis. Abrogation of mortalin-p53 interaction and reactivation of p53
      function could be a valid proposition for cancer therapy. In the present study,
      we first investigated in silico the interaction of withanone, a withanolide with
      anticancer activity, with mortalin. We found that withanone could bind to
      mortalin in a region, earlier predicted critical for binding to p53. Cationic
      rhodacyanine dye, MKT-077 has also shown to bind the same region and kill cancer
      cells selectively. We report the molecular dynamic simulations revealing the
      thermodynamic and structural stability of the withanone-mortalin complexes. We
      also demonstrate the experimental evidence of abrogation of mortalin-p53 complex
      by withanone resulting in nuclear translocation and functional reactivation of
      p53 in human cancer cells. The present study establishes a molecular interaction
      basis that could be used for screening and development of anticancer drugs with
      low toxicity to normal cells. Accurate knowledge of the 3D structure of mortalin
      would further enhance the potential of such analyses to understand the molecular
      basis of mortalin biology and mortalin based cancer therapy.

PMID- 22155303
TI  - Functional and structural characterization of a new serine protease with thrombin
      like activity TLBan from Bothrops andianus (Andean Lancehead) snake venom.
AB  - A new serine protease with thrombin-like activity (TLBan) from Bothrops andianus
      (Andean Lancehead) was isolated in two chromatographic steps in LC molecular
      exclusion and reverse phase-HPLC. TLBan is a glycoprotein that contains both N
      linked carbohydrates and sialic acid in its structure, with Mr ~29 kDa under
      reducing conditions and non-reducing ~25 kDa conditions and confirmed by MALDI
      TOF mass spectrometry (25,835.65 Da) and exhibited high specificity for BArhoNA,
      Michaelis-Menten behavior with Km 5.4 * 10(-1) M and the V(max) 7.9 * 10(-1)
      nmoles rho-NA/L/min for this substrate and high stability when was analyzed at
      different temperatures (25 to 60  degrees C), pHs (4.0 to 8.0), was inhibited by
      soybean trypsin inhibitor, EDTA and phenylmethylsulfonyl fluoride (PMSF). The
      total amino acid sequence was obtained through sequencing of selected tryptic
      peptides and by inference obtained using SwissProt database http://br.expasy.org/
      with the search restricted to serine proteases from Crotalinae snakes and show
      high amino acid sequence identity with other serine proteases from snake venom.
      TLBan showed the presence of His(44), Asp(91) residues and Ser was deduced (187)
      position, in the corresponding positions to the catalytic triad established in
      the serine proteases and Ser(187) are inhibited by phenylmethylsulfonyl fluoride
      (PMSF). In this work, we investigated the ability of TLBan to degrade fibrinogen
      and we observed that it is able to cause alpha- and beta-chain cleavage.
      Enzymatic activities as well as the platelet aggregation were strongly inhibited
      when were incubated with PMSF, a specific inhibitor of serine protease. TLBan
      showed a potential medical-scientific interest to understand the
      pathophysiological mechanism of the snake venom action and identification of new
      blood coagulation cascade acting enzymes of natural sources.

PMID- 22155304
TI  - Low molecular weight compounds from Zoanthus sociatus impair insulin secretion
      via Ca(+2) influx blockade and cause glucose intolerance in vivo.
AB  - Cnidarians comprise a taxon with a high biodiversity of cytolitic, neurotoxic and
      cardiotoxic compounds, which have not been studied on insulin release. We tested
      the effect of a crude extract of Zoanthus sociatus (Ellis, 1767) and the low
      molecular weight fraction of this extract on insulin secretion in isolated rat
      beta-cells and also in a glucose tolerance test in vivo. We observed that the
      extract inhibited insulin release by reducing the amount secreted by individual
      beta-cells and also by silencing a fraction of the secreting population. This
      effect coincided with a diminished rise of intracellular Ca(+2) in response to
      high glucose and high K+ -induced depolarization. Moreover intraperitoneal
      administration of the low molecular weight fraction produced glucose intolerance
      in adult rats. The active fraction exhibited molecular weights similar to the
      neurotoxins described in the phylum. Our results broaden the toxic effects of
      cnidarian venoms and show evidence of potential modulators of voltage-gated
      Ca(+2) channels in this group.

PMID- 22155305
TI  - JZTX-XIII, a Kv channel gating modifier toxin from Chinese tarantula Chilobrachys
      jingzhao.
AB  - Jingzhaotoxin-XIII (JZTX-XIII), a 35 residue polypeptide, with the ability to
      inhibit voltage-dependent potassium channels in the shab (Kv2) and shal (Kv4)
      subfamilies, was purified from the venom of the Chinese tarantula Chilobrachys
      jingzhao. Electrophysiological recordings carried out in Xenopus laevis oocytes
      showed that JZTX-XIII acted as gating modifier of voltage-dependent K+ channels
      which inhibited the Kv2.1 channel and Kv4.1 channel, with the IC50 value of 0.47
      MUM and 1.17 MUM, respectively. JZTX-XIII shares high sequence similarity with
      gating modifier toxins inhibiting a wide variety of ion channels including Nav1.5
      subtype, but it showed no Nav1.5 channel activity. Structure-function analysis
      indicates that the acidic residues of Glu10 and Glu17 in JZTX-XIII might be
      responsible for the loss of the Nav1.5 channel inhibitory potency for JZTX-XIII.

PMID- 22155306
TI  - WITHDRAWN: Adenoviral gene delivery can convert adult human fibroblasts to
      neurons.
AB  - This article has been withdrawn at the request of the authors. 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- 22155307
TI  - Heme oxygenase-1 mediates protective effects on inflammatory, catabolic and
      senescence responses induced by interleukin-1beta in osteoarthritic osteoblasts.
AB  - Osteoarthritis (OA) is a chronic degenerative joint disease showing altered bone
      metabolism. Osteoblasts contribute to the regulation of cartilage metabolism and
      bone remodeling. We have shown previously that induction of heme oxygenase-1 (HO
      1) protects OA cartilage against inflammatory and degradative responses. In this
      study, we investigated the effects of HO-1 induction on OA osteoblast metabolism.
      HO-1 was induced with cobalt protoporphyrin IX (CoPP) and by transduction with LV
      HO-1. In osteoblasts stimulated with interleukin (IL)-1beta, CoPP enhanced
      mineralization, the expression of a number of markers of osteoblast
      differentiation such as Runx2, bone morphogenetic protein-2, osteocalcin, and
      collagen 1A1 and 1A2, as well as the ratio osteoprotegerin/receptor activator of
      nuclear factor-kappaB ligand. HO-1 induction significantly reduced the expression
      of matrix metalloproteinase (MMP)-1, MMP-2 and MMP-3, and the production of pro
      inflammatory cytokines such as tumor necrosis factor-alpha and IL-6 whereas IL-10
      levels increased. HO-1 also exerted inhibitory effects on prostaglandin (PG)E(2)
      production which could be dependent on cyclooxygenase-2 and microsomal PGE
      synthase-1 down-regulation. The activity of senescence-associated beta
      galactosidase and the expression of the senescence marker caveolin-1 were
      significantly decreased after HO-1 induction. The inhibition of nuclear factor
      kappaB activation induced by IL-1beta in OA osteoblasts may contribute to some HO
      1 effects. Our results have shown that HO-1 decreases the production of relevant
      inflammatory and catabolic mediators that participate in OA pathophysiology thus
      eliciting protective effects in OA osteoblasts.

PMID- 22155308
TI  - Inactivation of a class A and a class C beta-lactamase by 6beta
      (hydroxymethyl)penicillanic acid sulfone.
AB  - beta-Lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) contribute
      significantly to the longevity of the beta-lactam antibiotics used to treat
      serious infections. In the quest to design more potent compounds and to
      understand the mechanism of action of known inhibitors, 6beta
      (hydroxymethyl)penicillanic acid sulfone (6beta-HM-sulfone) was tested against
      isolates expressing the class A TEM-1 beta-lactamase and a clinically important
      variant of the AmpC cephalosporinase of Pseudomonas aeruginosa, PDC-3. The
      addition of the 6beta-HM-sulfone inhibitor to ampicillin was highly effective.
      6beta-HM-sulfone inhibited TEM-1 with an IC(50) of 12 +/- 2 nM and PDC-3 with an
      IC(50) of 180 +/- 36 nM, and displayed lower partition ratios than commercial
      inhibitors, with partition ratios (k(cat)/k(inact)) equal to 174 for TEM-1 and 4
      for PDC-3. Measured for 20 h, 6beta-HM-sulfone demonstrated rapid, first-order
      inactivation kinetics with the extent of inactivation being related to the
      concentration of inhibitor for both TEM-1 and PDC-3. Using mass spectrometry to
      gain insight into the intermediates of inactivation of this inhibitor, 6beta-HM
      sulfone was found to form a major adduct of +247 +/- 5 Da with TEM-1 and +245 +/-
      5 Da with PDC-3, suggesting that the covalently bound, hydrolytically stabilized
      acyl-enzyme has lost a molecule of water (HOH). Minor adducts of +88 +/- 5 Da
      with TEM-1 and +85 +/- 5 Da with PDC-3 revealed that fragmentation of the
      covalent adduct can result but appeared to occur slowly with both enzymes. 6beta
      HM-sulfone is an effective and versatile beta-lactamase inhibitor of
      representative class A and C enzymes.

PMID- 22155309
TI  - Ozone induces synthesis of systemic prostacyclin by cyclooxygenase-2 dependent
      mechanism in vivo.
AB  - Under certain pathological conditions, e.g., infectious or neoplastic diseases,
      application of ozone exerts therapeutic effects. However, pharmacological
      mechanisms are not understood. Since an interaction with the arachidonic acid
      metabolism is suggested we investigated the effect of intraperitoneal
      insufflation of ozone on prostanoid system in vivo. Upon ozone application (4
      mg/kg) to rats we observed an approximate 3-fold increase in excretion rate of 6
      keto-prostaglandin (PG) F1alpha and of 2,3-dinor-6-keto-PG F1alpha, the
      measurable stable products of prostacyclin. In plasma and vessel tissue 6-keto-PG
      F1alpha concentration was also significantly increased. In contrast, excretion
      rates for PGE2 and thromboxane (TX) B2 did not change. F2-isoprostanes, regarded
      as endogenous indicators of oxidative stress, were also unaffected by ozone
      application. Oxygen insufflation used as control was without any effect on
      prostanoid levels. Ozone caused increase in 6-keto-PG F1alpha by arterial but not
      by venous vessel tissues with peak activity 6-9h following insufflation. The
      increase in PGI2 synthesis was dependent on cyclooxygenase (COX)-2 activity,
      demonstrated by its sensitivity towards COX-2 inhibition, and by enhanced COX-2
      mRNA and protein expression in vessels. Ozone exerted no rise in excretion rate
      of prostacyclin metabolites in COX-2(-/-) but in COX-1(-/-) mice. Enzymatic
      activity and mRNA expression of vascular PGI2 synthase (PGIS) was unaffected by
      ozone treatment. In summary our study shows for the first time that ozone
      insufflation causes enhanced expression of COX-2 in the vessel system leading to
      exclusive elevation of systemic PGI2 levels. We assume that PGI2 stimulation may
      contribute to the beneficial effects of ozone treatment.

PMID- 22155310
TI  - Euphol prevents experimental autoimmune encephalomyelitis in mice: evidence for
      the underlying mechanisms.
AB  - Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune
      inflammatory disease of the central nervous system (CNS), the existing therapy of
      which is only partially effective and is associated with undesirable side
      effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of
      pharmacological properties and is considered to have anti-inflammatory action.
      However there are no reports about the effects and mechanisms of euphol in
      experimental autoimmune encephalomyelitis (EAE), an established model of MS. Here
      we report the effects and the underlying mechanisms of action of euphol in EAE.
      Euphol (1-10mg/kg) was administered orally at different time-points of EAE.
      Immunological and inflammatory responses were evaluated by real-time PCR, Western
      blot and flow cytometry assays. We provide evidence that euphol significantly
      attenuates neurological signs of EAE. These beneficial effects of euphol seem to
      be associated with the down-regulation of mRNA and protein expression of some pro
      inflammatory mediators such as TNF-alpha, inducible nitric oxide synthase (iNOS)
      and cyclooxygenase-2 (COX-2) in the CNS. Furthermore, in vitro, euphol
      consistently inhibited the T cell-mediated immune response including the
      production of T(H)1 and T(H)17 cytokines in spleen cells of untreated EAE
      animals. Likewise, oral euphol treatment inhibited the infiltration of T(H)17
      myelin-specific cells into the CNS through the adhesion molecule, lymphocyte
      function-associated antigen 1 (LFA-1). Our findings reveal that oral
      administration of euphol consistently reduces and limits the severity and
      development of EAE. Therefore, euphol might represent a potential molecule of
      interest for the treatment of MS and other T(H)17 cell-mediated inflammatory
      diseases.

PMID- 22155311
TI  - Basal cell carcinoma which developed on the surface of recurrent parotid
      pleomorphic adenoma: coincidence or causality?

PMID- 22155312
TI  - Diversity analysis of methanogens in rumen of Bubalus bubalis by 16S riboprinting
      and sequence analysis.
AB  - The molecular diversity of rumen methanogens was investigated by 16S rDNA gene
      library prepared from the rumen contents obtained from Murrah buffaloes in India.
      Genomic DNA was isolated from adult male fistulated buffaloes and PCR conditions
      were set up using specific primers. Amplified product was cloned into a suitable
      vector, and the positive clones were selected assuming based on blue-white
      screening and sequenced. Positive clones were reamplified and the resulting PCR
      products were further subjected to Amplified Ribosomal DNA Restriction Analysis
      (ARDRA) by using HaeIII enzyme. A total of 108 clones were examined, and the
      analysis revealed 16 phylotypes. Out of sixteen phylotypes, nine phylotypes
      belong to the uncultured group of methanogens, and the rest of seven phylotypes
      belong to the order Methanomicrobiales, Methanococcales and Methanobacteriales.
      Out of the 108 rDNA clones, 66 clones which constitute 61.1% of the total clone
      representing 9 phylotypes, show less than 97% sequence similarity with any of the
      cultured strain of methanogens. The second largest group of clones (24 clones)
      represented by four phylotypes show a sequence similarity ranging from 91% to 99%
      with Methanomicrobium mobile strain of methanogens. The third group of 16S rDNA
      clones clustered along with M. burtonii strain of methanogens. This group
      consists of 6 clones and constitutes about 5.5% of the total clones and
      represented by only single phylotype. Fourth and fifth clusters of 16S rDNA
      clones consist of 5 and 7 clones respectively, and these were matched with
      Methanobrevibacter gottschalkii and Methanobrevibacter rumanatium strain of
      methanogens and constitute about 4.6% and 6.4% of the total clones.

PMID- 22155313
TI  - Carbon nanotubes provoke inflammation by inducing the pro-inflammatory genes IL
      1beta and IL-6.
AB  - Carbon nanotubes (CNTs) are largely produced and widely used because of their
      novel features, and the annual yield is expected to increase dramatically in the
      near future. Meanwhile, adverse health influences from exposure to CNTs are
      widely concerned, partially due to their asbestoid characteristics. In the
      current study, to assess the inflammatory responses and related mechanisms, we
      established a mouse model of chronic exposure to CNTs using intraperitoneal
      injection of single-walled carbon nanotubes (SWNTs) and multi-walled carbon
      nanotubes (MWNTs). Our results demonstrated the fibre-like pathogenic behaviors
      of CNTs, reflected by increased total protein content in the lavageate from
      peritoneal cavities and increased serum levels of inflammatory cytokines, IL
      1beta and IL-6. The pro-inflammatory effects of CNTs were further validated with
      exposure to in vitro cultured monocyte-macrophage cells, J774A.1, as SWNTs and
      MWNTs significantly increased the expression levels of pro-inflammatory genes IL
      1beta and IL-6. Collectively, our data demonstrate that SWNTs and MWNTs provoke
      considerable inflammation presumably due to their fibre-like shape, and further
      confirm the length- and size-related structure-activity relationship for CNTs in
      stimulating inflammatory responses.

PMID- 22155314
TI  - Analysis of the formation of flower shapes in wild species and cultivars of tree
      peony using the MADS-box subfamily gene.
AB  - Tree peony (Paeonia suffricotisa) cultivars have a unique character compared with
      wild species; the stamen petalody results in increased whorls of petals and
      generates different flower forms, which are one of the most important traits for
      cultivar classification. In order to investigate how petaloid stamens are formed,
      we obtained the coding sequence (666 bp) and genomic DNA sequence of the PsTM6
      genes (belongs to B subfamily of MADS-box gene family) from 23 tree peony
      samples, Five introns and six exons consisted of the genomic DNA sequence. The
      analysis of cis-acting regulatory elements in the third and fourth intron
      indicated that they were highly conserved in all samples. Partial putative amino
      acids were analyzed and the results suggested that functional differentiation of
      PsTM6 paralogs apparently affected stamen petalody and flower shape formation due
      to due to amino acid substitution caused by differences in polarity and
      electronic charge. Sliding window analysis indicated that the different regions
      of PsTM6 were subjected to different selection forces, especially in the K
      domain. This is the first attempt to investigate genetic control of the stamen
      petalody based on the PsTM6 sequence. This will provide a basis for understanding
      the evolution of PsTM6 and its the function of in determining stamen morphology
      of tree peony.

PMID- 22155315
TI  - Isolation of single, intact chromosomes from single, selected ovarian cancer
      cells for in situ hybridization and sequencing.
AB  - The first step towards effective therapy of cancer is to reveal molecular
      profiles of all cell clones propelling tumor growth. The specific aim of this
      project was to develop a technology helping us to isolate patient's single,
      living cells based upon their cancer-specific, cell surface biomarkers, to reveal
      their molecular profiles, and to isolate, from these selected cells, intact
      chromosomes for in situ hybridization (FISH) and for next generation sequencing
      (NGS). We attained this aim, while probing the cells from the ovarian cancer
      patients. Ovarian cancer is the most deadly of all gynecological cancers. In most
      of the patients with the advanced stages of this cancer, the gene for epidermal
      growth factors receptor (EGFR) is mutated, as the deletion variant III, resulting
      in the truncated transcripts and products. From these patients, we collected
      cells from peritoneal fluid, blood, lymph, and biopsies. We genetically
      engineered fluorescent and superparamagnetic single chain variable fragments
      (scFvs) targeting EGFRwt and EGFRvIII. Using these scFvs, we isolated single,
      living ovarian cancer cells and analyzed their transcripts and products. We
      further genetically engineered scFv targeting dsDNA. Using these scFvs, we
      isolated the entire single, intact chromosomes from the selected, single ovarian
      cancer cells for NGS and for liquid phase FISH. This novel work-flow opens new
      routes not only for molecular profiling of the entire spectrum of cancer cell
      clones in the diagnosed patient, one cell clone at a time, but also for
      manufacturing targeted contrast for in vivo imaging and for designing and guiding
      targeted delivery of therapeutic genes in cancer therapy.

PMID- 22155316
TI  - Adiponectin gene polymorphisms (T45G and G276T), adiponectin levels and risk for
      metabolic diseases in an Arab population.
AB  - In this study we examined the association of adiponectin gene variants with
      circulating adiponectin, and known metabolic diseases in 298 healthy controls and
      297 Saudi subjects with type 2 diabetes mellitus (T2DM). Anthropometric and
      biochemical parameters were measured by standard procedures. Genotyping of T45G
      and G276T single nucleotide polymorphisms of adiponectin gene was carried out by
      PCR-RFLP analysis. No significant differences in the genotype distribution of
      T45G and G276T polymorphism were found between control and diabetic subjects.
      Neither SNP conferred an association with T2DM, obesity, hypertension or
      dyslipidemia. Despite a marked decrease in patients as opposed to controls,
      adiponectin levels were not different according to genotypes of T45G and G276T
      polymorphisms in control and patients. Thus, neither adiponectin SNPs
      independently conferred increased T2DM risk nor in other metabolic conditions
      considered such as obesity, hypertension or dyslipidemia. These findings support
      the existence of population based differences in the association of adiponectin
      gene variants with metabolic phenotypes and emphasize the importance of studying
      multiple polymorphisms, sufficient enough to identify the adiponectin gene as a
      genetic marker for several non-chronic communicable diseases.

PMID- 22155317
TI  - Antisense oligonucleotide corrects splice abnormality in hereditary myopathy with
      lactic acidosis.
AB  - Hereditary myopathy with lactic acidosis (HML) (OMIM #255125) presents in
      childhood with exercise intolerance and muscle pain on trivial exercise, lactic
      acidosis, dyspnoea, palpitations, and rhabdomyolysis which can be fatal. The
      disease is recessively inherited and caused by a deep intronic, single base
      transition in the iron-sulfur cluster scaffold, ISCU gene that causes retention
      of a pseudoexon and introduction of a premature termination codon. IscU protein
      deficiency causes secondary defects in several iron-sulfur dependant proteins,
      including enzymes involved in aerobic energy metabolism. We have shown in a
      previous study that the splice abnormality affects skeletal muscle more than
      other tissues, leading to the purely muscular phenotype. Antisense
      oligonucleotides (AOs) have been able to redirect mRNA splicing in a number of
      disease models, and show promise in clinical studies. We designed 2'O-methyl
      phosphorothioate AOs targeting either splice site of the detrimental HML
      pseudoexon. The acceptor site AO effectively redirected splicing towards the
      normal state in cultured muscle fibroblasts, whilst the donor site AO promoted
      pseudoexon inclusion in both patient and control cells. Our results show that AO
      therapy seems feasible in HML, but care must be taken to avoid adverse splicing
      effects.

PMID- 22155318
TI  - Fas ligand expression and mediated activation of an apoptosis program in bovine
      follicular granulosa cells.
AB  - Fas ligand (FasL) is a cytokine that may be expressed as a transmembrane ligand
      at the cell surface, and induces apoptosis by binding to the Fas. Ovarian
      follicular atresia and luteolysis are thought to occur by apoptosis. To reveal
      the intracellular signal transduction molecules involved in the process of
      follicular development in the bovine ovary, FasL gene without the stop codon was
      amplified and directly cloned into pAcGFP-N1. The resultant recombinant plasmid
      pAcGFP-bFasL was then transfected into bovine follicular granulosa cells. The
      transcription and translation of FasL were detected by RT-PCR and Western blot
      analysis. The methyl-tetrazolium (MTT) assay, Hoechst33342 staining, and DNA
      Ladder method were performed to determine the growth inhibition and apoptosis of
      the cells. The real-time quantitative PCR assay was performed to measure the
      expression of FasL in vivo in granulosa cells collected from diverse stage of
      dominant and atretic follicles. The results showed that the FasL fusion gene was
      successfully expressed in granulosa cells as evidenced by the detection of a 847
      bp fragment corresponding to the FasL mRNA by RT-PCR and a 59 kDa band
      corresponding to the FasL fusion protein by Western blot. Granulosa cell
      viability decreased significantly at 72 h after transfection, and the apoptosis
      rate of the cells transfected with pAcGFP-FasL was significantly higher than that
      of the control group. Cells in the FasL transfection group showed ladder patterns
      characteristic of apoptosis, and the nuclei were shrunken and densely
      hyperchromatic or fragmented. In addition, FasL was highly expressed in granulosa
      cells of atretic follicle than dominant follicle in vivo. We found that FasL is
      capable of inhibiting the proliferation of bovine follicular granulosa cells and
      inducing cell apoptosis in vitro and in vivo when over-expressed. This study will
      aid in further understanding the mechanism of regulation of FasL on bovine oocyte
      formation and development.

PMID- 22155319
TI  - Fetal exposure to propoxur and abnormal child neurodevelopment at 2 years of age.
AB  - OBJECTIVE: Our aim was to determine the effects of fetal exposure to propoxur and
      pyrethroids, on child neurodevelopment at 2 years of age. PATIENTS AND METHODS:
      Mothers were prospectively recruited during mid-pregnancy in Bulacan, Philippines
      where multiple pesticides including propoxur, cyfluthrin, chlorpyrifos,
      cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin
      are used. To detect prenatal exposure to these pesticides, maternal hair and
      blood, infant's hair, cord blood, and meconium were analyzed for the pesticides
      by gas chromatography/mass spectrometry. Infants were examined at 2 years of age
      with 95.1% follow up rate and their neurodevelopment outcome was assessed by the
      Griffiths mental developmental scale (N=754). RESULTS: Meconium analysis was the
      most sensitive method to detect fetal exposure to pesticides and exposure was
      highest for propoxur (21.3%) and the grouped pyrethroids (2.5% - bioallethrin,
      transfluthrin, cyfluthrin and cypermethrin). Path analysis modeling was performed
      to determine the effects of fetal exposure to propoxur and pyrethroids on the
      child's neurodevelopment at 24 months of age while controlling for confounders.
      Only singletons and those with complete data for the path analysis were included
      (N=696). Using a path analysis model, there was a significant negative (beta=
      0.14, p<0.001) relationship between prenatal pesticide exposure to propoxur and
      motor development at 2 years of age after controlling for confounders, e.g.,
      infant gender, socioeconomic status, maternal intelligence, home stimulation
      (HOME), postnatal exposure to propoxur and blood lead level at 2 years of age.
      CONCLUSION: At 2 years of age, prenatal exposure to propoxur was associated with
      poorer motor development in children.

PMID- 22155320
TI  - Kaempferol protects against doxorubicin-induced cardiotoxicity in vivo and in
      vitro.
AB  - The long-term clinical usefulness of doxorubicin (DOX), an anthracycline with
      potent antitumor activity, is limited by DOX-induced cardiotoxicity. Kaempferol,
      one of the most common dietary flavonoids, is known to have anti-apoptotic, anti
      oxidative, and anti-inflammatory properties. The current study aimed to
      investigate the possible protective effect of kaempferol against DOX-induced
      cardiotoxicity and the underlying mechanisms. Rats were intraperitoneally (i.p.)
      treated with DOX (3 mg/kg) every other day for a cumulative dose of 9 mg/kg.
      After 28 days, DOX caused retarded body and heart growth, oxidative stress,
      apoptotic damage, mitochondrial dysfunction, and Bcl-2 expression disturbance. In
      contrast, kaempferol pretreatment (10 mg/kg i.p. before DOX administration)
      attenuated the DOX-induced apoptotic damage in heart tissues. In vitro studies
      also indicated that kaempferol may have used the mitochondrion-dependent pathway
      to counteract the DOX-induced cardiotoxicity. This counteraction was achieved by
      inhibiting p53 expression and its binding to the promoter region of the Bax
      proapoptotic gene, but not to the Bcl-2 antiapoptotic gene. Kaempferol also
      effectively suppressed DOX-induced extracellular signal-regulated kinase (ERK)
      1/2 activation, but had no effect on p38 and JNK. Therefore, kaempferol protected
      against DOX-induced cardiotoxicity, at least, partially, by inhibiting the
      activation of p53-mediated, mitochondrion-dependent apoptotic signaling, and by
      being involved in an ERK-dependent mitogen-activated protein kinase pathway.
      These findings elucidated the potential of kaempferol as a promising reagent for
      treating DOX-induced cardiotoxicity, and may have implications in the long-term
      clinical usefulness of DOX.

PMID- 22155321
TI  - Microbubbles during pulmonary vein radiofrequency ablation.

PMID- 22155322
TI  - Using omega-3 fatty acids to treat persistent atrial fibrillation: time to fish
      or cut bait?

PMID- 22155323
TI  - Immune responses and protection in catla (Catla catla) vaccinated against
      epizootic ulcerative syndrome.
AB  - Three different antigenic preparations from the epizootic ulcerative syndrome
      (EUS) pathogen Aphanomyces invadans were evaluated as vaccine candidate in catla
      (Catla catla). Anti-catla enzyme immunoconjugate was prepared after isolating
      catla immunoglobulin and raising hyperimmune sera against it, in rabbit. Three
      antigens namely, fungal extract (FE), fungal extract mixed with Freund's
      incomplete adjuvant (FIA) in a 1:1 (v/v) ratio (FE + A) and extra cellular
      product (ECP) were prepared and three groups of catla were vaccinated
      intramuscularly with all these antigens (200 MUg/fish). Different cellular and
      humoral immune responses were measured for the entire vaccinated and control
      group on 0th, 5th, 15th and 25th day post vaccination. Thirty days after the
      vaccination, the fish were challenged with an A. invadans zoospore dose of 1 *
      10(5) ml(-1) and mortality and relative percent of survival (RPS) were recorded.
      Study of cellular immunological parameters including antigen-specific leukocyte
      proliferation, antigen-specific nitric oxide production and superoxide anion
      production showed significantly higher (p < 0.05) values, in general, on 5th and
      15th day post vaccination than the 0th day. Among all the antigenic groups, FE +
      A showed most significant response compared to the other groups. Among the
      humoral immune responses, lysozyme activity showed almost similar trend like
      cellular parameters. Anti-Aphanomyces antibody production was measured by enzyme
      linked immunosorbent assay (ELISA) and it was increased with increasing days of
      vaccination in all the vaccinated groups with the highest observed on 25th day.
      Among the antigens, FE + A showed the highest antibody production following
      vaccination. The result of the homologous pathogen challenge study showed
      reduction in mortality in all the vaccinated groups. However, this reduction was
      not statistically significant (p > 0.05). Increased immune responses and
      protection have important implications with regard to the control of EUS by
      vaccination.

PMID- 22155324
TI  - Steady-state evoked potentials as an index of multisensory temporal binding.
AB  - Temporal congruency promotes perceptual binding of multisensory inputs. Here, we
      used EEG frequency-tagging to track cortical activities elicited by auditory and
      visual inputs separately, in the form of steady-state evoked potentials (SS-EPs).
      We tested whether SS-EPs could reveal a dynamic coupling of cortical activities
      related to the binding of auditory and visual inputs conveying synchronous vs.
      non-synchronous temporal periodicities, or beats. The temporally congruent
      audiovisual condition elicited markedly enhanced auditory and visual SS-EPs, as
      compared to the incongruent condition. Furthermore, an increased inter-trial
      phase coherence of both SS-EPs was observed in that condition. Taken together,
      these observations indicate that temporal congruency enhances the processing of
      multisensory inputs at sensory-specific stages of cortical processing, possibly
      through a dynamic binding by synchrony of the elicited activities and/or improved
      dynamic attending. Moreover, we show that EEG frequency-tagging with SS-EPs
      constitutes an effective tool to explore the neural dynamics of multisensory
      integration in the human brain.

PMID- 22155326
TI  - Chronometry of word and picture identification: common and modality-specific
      effects.
AB  - Based on a previous fMRI connectivity analysis, we previously proposed that long
      distance connections between left inferior frontal sulcus and left
      occipitotemporal sulcus mediate access to visual short-term memory both for
      written words and pictures enhancing conscious perception and successful encoding
      in an amodal manner. Using a 64-channel event-related potential electrode system
      in 19 young cognitively intact volunteers, we determined the chronometry of
      common and input-modality specific effects of word and picture identification and
      subsequent memory retrieval. Stimulus durations were calibrated per subject,
      modality and run so as to reach a 50% positive identification report. The
      earliest main effect of a positive identification report occurred between 180 and
      200 ms, was common for both input-modalities, had a positive polarity and was
      located at around CPz. This effect was followed between 270 and 450 ms by
      additional common positive-polarity effects at centrofrontal electrode sites and
      by common negative effects at P7/P8, TP7/TP8 and T8. Each of the later effects
      was closely associated not only with identification but also with subsequent
      memory retrieval. The earliest input-modality specific effect of conscious
      identification that we detected occurred from 280 till 440 ms at P8. Our findings
      are in line with a model where the initial stages of perceptual identification
      and visual short-term memory access rely on long-distance connections that are
      shared between written words and pictures.

PMID- 22155325
TI  - Myelin water imaging reflects clinical variability in multiple sclerosis.
AB  - Whilst MRI is routinely used for the assessment and diagnosis of multiple
      sclerosis, there is poor correspondence between clinical disability in primary
      progressive multiple sclerosis (PPMS) patients and conventional MRI markers of
      disease activity (e.g., number of enhancing lesions). As PPMS patients show
      diffuse and global myelin loss, the aim of this study was to evaluate the
      efficacy of whole-brain myelin water fraction (MWF) imaging in PPMS.
      Specifically, we sought to use full-brain analysis techniques to: 1) determine
      the reproducibility of MWF estimates in PPMS brain; 2) compare MWF values in PPMS
      brain to healthy controls; and 3) establish the relationship between MWF and
      clinical disability, regionally and globally throughout the brain. Seventeen PPMS
      patients and seventeen age-matched controls were imaged using a whole-brain multi
      component relaxation imaging technique to measure MWF. Analysis of MWF reduction
      was performed on three spatial levels: 1) histogram; 2) white matter skeleton;
      and 3) voxel-wise at the single-subject level. From histogram analysis, PPMS
      patients had significantly reduced global normal appearing white matter MWF (6%,
      p=0.04) compared to controls. Focal lesions showed lower MWF values than white
      matter in controls (61%, p<0.001) and patients (59%, p<0.001). Along the white
      matter skeleton, MWF was diffusely reduced throughout the PPMS brain, with
      significant correlations between reduced MWF and increased clinical disability
      (more severe symptoms), as measured by the Expanded Disability Status Scale,
      within the corpus callosum and frontal, temporal, parietal and occipital white
      matter. Correlations with the more specific mental and sensory functional system
      scores were localized to clinically eloquent locations: reduced MWF was
      significantly associated with increased mental scores in anterior regions (i.e.,
      frontal lobes and genu of the corpus callosum), and increased sensory scores in
      more posterior regions closer to the sensory cortex. Individual patient MWF maps
      were also compared to a normative population atlas, which highlighted areas of
      statistical difference between the individual patient and the population mean. A
      significant correlation was found between the volume of significantly reduced MWF
      and clinical disability (p=0.008, R=0.58). Our results show that clinical
      disability is reflected in particular regions of cerebral white matter that are
      consistent between subjects, and illustrates a method to examine tissue
      alteration throughout the brain of individual patients. These results strongly
      support the use of MWF imaging to evaluate disease activity in PPMS.

PMID- 22155327
TI  - Negative BOLD signal changes in ipsilateral primary somatosensory cortex are
      associated with perfusion decreases and behavioral evidence for functional
      inhibition.
AB  - We used functional magnetic resonance imaging (fMRI) and positron emission
      tomography (PET) to study the negative blood oxygenation level dependent (BOLD)
      signal and its underlying blood flow changes in healthy human subjects. This was
      combined with psychophysiological measurements to test that the negative BOLD
      signal is associated with functional inhibition. Electrical stimulation of the
      median nerve at 7 Hz evoked robust negative BOLD signals in the primary
      somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals
      in contralateral SI. The negative BOLD signal in ipsilateral SI was accompanied
      by commensurate decreases in relative regional cerebral blood flow (rCBF).
      Conjunction analysis of the fMRI and PET data revealed a region in the
      ipsilateral postcentral gyrus showing overlap of negative BOLD signals and
      relative rCBF decreases. The current perception threshold (CPT) at the
      ipsilateral finger during concomitant stimulation of the contralateral median
      nerve increased significantly, suggesting augmented functional inhibition. Since
      the CPT in the ipsilateral hallux did not significantly change in response to
      median nerve stimulation, it is more likely that the CPT-increase for the finger
      is due to functional inhibition (Kastrup et al., 2008) than to changes in
      selective attention. In conclusion, our data provide evidence that stimulus
      induced reductions in relative rCBF may underlie the negative BOLD signal, which
      in turn may reflect increments in functional inhibition.

PMID- 22155330
TI  - Correction of gradient echo images for first and second order macroscopic signal
      dephasing using phase derivative mapping.
AB  - Gradient echo techniques are often hampered by signal dephasing due to
      macroscopic phase perturbations because of system imperfections (shimming) or
      object induced perturbations of the magnetic field (hemorrhagic lesions,
      calcified tissue, air-tissue interfaces). Many techniques have been proposed to
      reduce the effects of macroscopic phase variations. Among these techniques are
      tuned pulse sequences, fitting techniques and reconstruction algorithms. These
      methods, however, suffer from one or more of the following drawbacks: they
      require longer acquisition times, require additional acquisitions, compensate
      only locally, can only be applied to multi-gradient echo data or may result in
      inaccurate results. In this work a generally applicable post-processing technique
      is presented to evaluate and compensate signal alterations invoked by first and
      second order macroscopic phase incoherences. In this technique, the derivatives
      of the signal phase are determined by applying the Fourier derivative theorem on
      the complex data. As a result, the phase derivatives are obtained without phase
      unwrapping and without compromising the resolution. The method is validated for
      single and multi-echo acquisitions by experiments on a co-axial cylinder phantom
      with known macroscopic field disturbances. The potential of the method is
      demonstrated on a multi-gradient echo acquisition on the head of a human
      volunteer. In general a first order correction is shown to be sufficient, however
      higher order correction is found to be beneficial near sharp transitions of the
      magnetic field.

PMID- 22155328
TI  - From novel to familiar: tuning the brain for metaphors.
AB  - Metaphors are fundamental to creative thought and expression. Newly coined
      metaphors regularly infiltrate our collective vocabulary and gradually become
      familiar, but it is unclear how this shift from novel to conventionalized meaning
      happens in the brain. We investigated the neural career of metaphors in a
      functional magnetic resonance imaging study using extensively normed new
      metaphors and simulated the ordinary, gradual experience of metaphor
      conventionalization by manipulating participants' exposure to these metaphors.
      Results showed that the conventionalization of novel metaphors specifically tunes
      activity within bilateral inferior prefrontal cortex, left posterior middle
      temporal gyrus, and right postero-lateral occipital cortex. These results support
      theoretical accounts attributing a role for the right hemisphere in processing
      novel, low salience figurative meanings, but also show that conventionalization
      of metaphoric meaning is a bilaterally-mediated process. Metaphor
      conventionalization entails a decreased neural load within semantic networks
      rather than a hemispheric or regional shift across brain areas.

PMID- 22155329
TI  - A general analysis of calibrated BOLD methodology for measuring CMRO2 responses:
      comparison of a new approach with existing methods.
AB  - The amplitude of the BOLD response to a stimulus is not only determined by
      changes in cerebral blood flow (CBF) and oxygen metabolism (CMRO(2)), but also by
      baseline physiological parameters such as haematocrit, oxygen extraction fraction
      (OEF) and blood volume. The calibrated BOLD approach aims to account for this
      physiological variation by performing an additional calibration scan. This
      calibration typically consists of a hypercapnia or hyperoxia respiratory
      challenge, although we propose that a measurement of the reversible transverse
      relaxation rate, R(2)', might also be used. A detailed model of the BOLD effect
      was used to simulate each of the calibration experiments, as well as the
      activation experiment, whilst varying a number of physiological parameters
      associated with the baseline state and response to activation. The effectiveness
      of the different calibration methods was considered by testing whether the BOLD
      response to activation scaled by the calibration parameter combined with the
      measured CBF provides sufficient information to reliably distinguish different
      levels of CMRO(2) response despite underlying physiological variability. In
      addition the effect of inaccuracies in the underlying assumptions of each
      technique were tested, e.g. isometabolism during hypercapnia. The three primary
      findings of the study were: 1) The new calibration method based on R(2)' worked
      reasonably well, although not as well as the ideal hypercapnia method; 2) The
      hyperoxia calibration method was significantly worse because baseline haematocrit
      and OEF must be assumed, and these physiological parameters have a significant
      effect on the measurements; and 3) the venous blood volume change with activation
      is an important confounding variable for all of the methods, with the hypercapnia
      method being the most robust when this is uncertain.

PMID- 22155331
TI  - The neural correlates of gist-based true and false recognition.
AB  - When information is thematically related to previously studied information, gist
      based processes contribute to false recognition. Using functional MRI, we
      examined the neural correlates of gist-based recognition as a function of
      increasing numbers of studied exemplars. Sixteen participants incidentally
      encoded small, medium, and large sets of pictures, and we compared the neural
      response at recognition using parametric modulation analyses. For hits, regions
      in middle occipital, middle temporal, and posterior parietal cortex linearly
      modulated their activity according to the number of related encoded items. For
      false alarms, visual, parietal, and hippocampal regions were modulated as a
      function of the encoded set size. The present results are consistent with prior
      work in that the neural regions supporting veridical memory also contribute to
      false memory for related information. The results also reveal that these regions
      respond to the degree of relatedness among similar items, and implicate
      perceptual and constructive processes in gist-based false memory.

PMID- 22155332
TI  - Creation of a blood-compatible surface: a novel strategy for suppressing blood
      activation and coagulation using a nitroxide radical-containing polymer with
      reactive oxygen species scavenging activity.
AB  - Various polymeric materials have been used in medical devices, including blood
      contacting artificial organs. Contact between blood and foreign materials causes
      blood cell activation and adhesion, followed by blood coagulation. Concurrently,
      the activated blood cells release inflammatory cytokines together with reactive
      oxygen species (ROS). We have hypothesized that the suppression of ROS generation
      plays a crucial role in blood activation and coagulation. To confirm this
      hypothesis, surface-coated polymers containing nitroxide radical compounds
      (nitroxide radical-containing polymers (NRP)) were designed and developed. The
      NRP was composed of a hydrophobic poly(chloromethylstyrene) (PCMS) chain to which
      2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) moieties were conjugated via
      condensation reaction of the chloromethyl groups in PCMS with the sodium
      alcoholate group of 4-hydroxy-TEMPO. Blood compatibility was investigated by
      placing NRP-coated beads in contact with rat whole blood. The amount of ROS
      generated on PCMS-coated beads used as a control increased significantly with
      time, while NRP-coated beads suppressed ROS generation. It is interesting to note
      that the suppression of inflammatory cytokine generation by NRP-coated beads was
      shown to be significantly higher than that by PCMS-coated beads. Both platelet
      and leukocyte adhesion to the beads were suppressed with increasing TEMPO
      incorporation in the polymer. These results confirm that the suppression of ROS
      by NRP prevents inflammatory cytokine generation, which in turn results in the
      suppression of blood activation and coagulation on the beads.

PMID- 22155333
TI  - A new use for an old method: the Woelcke myelin stain for counting degenerating
      neurons in the brain of mice following status epilepticus.
AB  - The Woelcke method is classically used for myelin staining. Degenerating neurons
      can be revealed histologically by hemalun and phloxin (H&P) where they appear
      "eosinophilic". In the first 24 h following soman-induced status epilepticus, we
      observed that the Woelcke method also revealed condensed, dark blue/black cells
      (W+ cells) in the gray matter of brain regions known to be sites of seizure
      related brain damage, marked by the presence of eosinophilic cells. In the
      present study, using adjacent brain sections alternately stained with either the
      Woelcke or the H&P method, we show that eosinophilic cells and W+ cells are the
      same degenerating cells. Moreover, we show that semi-automated quantitative
      evaluation of W+ cells through computerized image analysis is considerably easier
      and faster than that of eosinophilic cells. It is therefore concluded that the
      Woelcke technique could be very useful, especially for quantifying acute brain
      cell damage following status epilepticus.

PMID- 22155334
TI  - Querying temporal clinical databases on granular trends.
AB  - This paper focuses on the identification of temporal trends involving different
      granularities in clinical databases, where data are temporal in nature: for
      example, while follow-up visit data are usually stored at the granularity of
      working days, queries on these data could require to consider trends either at
      the granularity of months ("find patients who had an increase of systolic blood
      pressure within a single month") or at the granularity of weeks ("find patients
      who had steady states of diastolic blood pressure for more than 3 weeks").
      Representing and reasoning properly on temporal clinical data at different
      granularities are important both to guarantee the efficacy and the quality of
      care processes and to detect emergency situations. Temporal sequences of data
      acquired during a care process provide a significant source of information not
      only to search for a particular value or an event at a specific time, but also to
      detect some clinically-relevant patterns for temporal data. We propose a general
      framework for the description and management of temporal trends by considering
      specific temporal features with respect to the chosen time granularity. Temporal
      aspects of data are considered within temporal relational databases, first
      formally by using a temporal extension of the relational calculus, and then by
      showing how to map these relational expressions to plain SQL queries. Throughout
      the paper we consider the clinical domain of hemodialysis, where several
      parameters are periodically sampled during every session.

PMID- 22155335
TI  - BOAT: automatic alignment of biomedical ontologies using term informativeness and
      candidate selection.
AB  - The biomedical sciences is one of the few domains where ontologies are widely
      being developed to facilitate information retrieval and knowledge sharing, but
      there still remains the problem that applications using different ontologies
      cannot share knowledge without explicit references between overlapping concepts.
      Ontology alignment is the task of identifying such equivalence relations between
      concepts across ontologies. Its application to the biomedical domain should
      address two open issues: (1) determining the equivalence of concept-pairs which
      have overlapping terms in their names, and (2) the high run-time required to
      align large ontologies which are typical in the biomedical domain. To address
      them, we present a novel approach, named the Biomedical Ontologies Alignment
      Technique (BOAT), which is state-of-the-art in terms of F-measure, precision and
      speed. A key feature of BOAT is that it considers the informativeness of each
      component word in the concept labels, which has significant impact on biomedical
      ontologies, resulting in a 12.2% increase in F-measure. Another important feature
      of BOAT is that it selects for comparison only concept pairs that show high
      likelihoods of equivalence, based on the similarity of their annotations. BOAT's
      F-measure of 0.88 for the alignment of the mouse and human anatomy ontologies is
      on par with that of another state-of-the-art matcher, AgreementMaker, while
      taking a shorter time.

PMID- 22155336
TI  - Possible net harms of breast cancer screening: updated modelling of Forrest
      report.
AB  - OBJECTIVE: To assess the claim in a Cochrane review that mammographic breast
      cancer screening could be doing more harm than good by updating the analysis in
      the Forrest report, which led to screening in the United Kingdom. DESIGN:
      Development of a life table model, which replicated Forrest's results before
      updating and extending them with data from relevant systematic reviews, trials,
      and other models based on purposive literature searches. PARTICIPANTS: Women aged
      50 and over invited for breast cancer screening. MAIN OUTCOME MEASURES: Quality
      adjusted life years (QALYs), combining life years gained from screening with
      losses of quality of life from false positive diagnoses and surgery. RESULTS:
      Inclusion of the effects of harms reduced the updated estimate of net cumulative
      QALYs gained after 20 years from 3301 to 1536 or by more than half. The best
      estimates from the Cochrane review generated negative QALYs for the first seven
      years of screening, 70 QALYs after 10 years, and 834 QALYs after 20 years.
      Sensitivity analysis showed these results were robust to a range of assumptions,
      particularly up to 10 years. It also indicated the importance of the level and
      duration of harms from surgery. CONCLUSIONS: This analysis supports the claim
      that the introduction of breast cancer screening might have caused net harm for
      up to 10 years after the start of screening.

PMID- 22155337
TI  - Contribution of complex stapes motion to cochlea activation.
AB  - Classic theories of hearing have considered only a translational component
      (piston-like component) of the stapes motion as being the effective stimulus for
      cochlear activation and thus the sensation of hearing. Our previous study (Huber
      et al., 2008) qualitatively showed that rotational components around the long and
      short axes of the footplate (rocking-like components) lead to cochlear activation
      as well. In this study, the contribution of the piston-like and rocking-like
      components of the stapes motion to cochlea activation was quantitatively
      investigated with measurements in live guinea pigs and a related mathematical
      description. The isolated stapes in anesthetized guinea pigs was stimulated by a
      three-axis piezoelectric actuator, and 3-D motions of the stapes and compound
      action potential (CAP) of the cochlea were measured simultaneously. The measured
      values were used to fit a hypothesis of the CAP as a linear combination of the
      logarithms of the piston-like and rocking-like components. Both the piston-like
      and rocking-like components activate cochlear responses when they exceed certain
      thresholds. These thresholds as well as the relation between CAP and intensity of
      the motion component were different for piston-like and rocking-like components.
      The threshold was found to be higher and the sensitivity lower for the rocking
      like component than the corresponding values for the piston-like component. The
      influence of the rocking-like component was secondary in cases of piston-dominant
      motions of the stapes although it may become significant for low amplitudes of
      the piston-like component.

PMID- 22155338
TI  - Re: Socioeconomic status and subclinical atherosclerosis in older adults.

PMID- 22155339
TI  - A comparison of cell-collecting methods for the Comet assay in urinary bladders
      of rats.
AB  - Conducting the single-cell gel electrophoresis (Comet) assay in the urinary
      bladders of rodents is technically problematic because the bladder is small and
      thin, which makes it difficult to collect its mucosal cells by scraping. We
      performed the Comet assay using a simple mincing method in which tissues are
      minced with scissors. We then compared data obtained with this method with data
      obtained using the scraping method. Sprague-Dawley rats of both sexes were orally
      given twice the known carcinogens N-methyl-N-nitrosourea (MNU), ethyl
      methanesulfonate (EMS), or o-anisidine (OA). Three hours after the second
      administration, the bladder of each rat was divided into two parts and each part
      was processed by either the mincing or the scraping method. Both mincing and
      scraping methods detected DNA damage in MNU-, EMS-, but not OA-treated rats, and
      thus the mincing method had a sufficient capability to detect DNA damaging
      agents. The morphological analysis of the prepared cell suspensions revealed that
      more than 80% of the cells collected by the mincing method were from the
      epithelium. Because the mincing method requires only one-half of a bladder, the
      other half remains intact and can be used for histopathological examination. We
      conclude that the mincing method is easier and more appropriate for the Comet
      assay in urinary bladder tissue than the scraping method.

PMID- 22155340
TI  - Therapeutic strategies in multiple sclerosis.

PMID- 22155341
TI  - Comparison of acid and enzymatic methods for inulin dosage: analytical
      performances and impact on glomerular filtration rate evaluation.
AB  - Among issues susceptible to hamper a reliable measurement of inulin clearance,
      those regarding the dosage of inulin are largely neglected. We have compared the
      analytical performances of 2 commonly used methods of inulin dosage (one "acid"
      and one "enzymatic" method) and studied their potential impact on the glomerular
      filtration rate (GFR) value given by inulin clearance. Repeatability, uncertainty
      and the beta-expectation limits were evaluated from pre-determined serum and
      urine pools of inulin. Agreement between the two methods was analyzed from 99
      inulin clearances performed in renal transplant patients. Impact of the method of
      dosage on GFR evaluation was simulated according to the respective beta
      expectations limits of each method. Overall, intra-assay coefficient of
      variability and relative bias were inferior to 5% and 10% for both methods.
      Contrary to the acid method, analytical performance of the enzymatic method was
      not influenced by the presence of glucose. The relative difference in GFR values
      obtained with the two methods in transplant patients was -0.4 +/- 10%.
      Simulations suggested that changes in inulin concentration attributable to
      analytical error could modify the value of GFR from -12% to +28%. In conclusion,
      while analytical performances are globally acceptable for both methods, they are
      not strictly equivalent. The impact on the determination of GFR, albeit limited,
      is not negligible and adds to other sources of inaccuracy. International
      standardization for the dosage of inulin is necessary.

PMID- 22155342
TI  - Chimerism detection by short tandem repeat analysis when donor and recipient
      genotypes are not known.
AB  - BACKGROUNDS: The analysis of chimerism after bone marrow transplantation by STR
      PCR is frequently carried out with commercial kits designed for forensic purposes
      and including too many non informative STR. Furthermore, in routine clinical
      practice it is not uncommon to lack the pre-transplant genotype of the recipient
      or the donor, thus making it difficult to identify both components in the post
      transplant genotype. The objective of this paper is to overcome these drawbacks
      by analyzing the informativity of STR markers from a perspective which can be
      applied whether the pretransplant genotypes are available or not, and selecting a
      minimum STR panel that allows an effective direct detection of chimerism.
      METHODS: DNA extraction, STR-PCR and fragment analysis of 15 STR in 90 donor
      recipient pairs, 60 of which were part of the discovery set and 30 in a
      validation set. Loci were considered as informative when there were 3 or 4
      different alleles in the combined genotypes of the recipient and the donor.
      RESULTS: The informativity varied between 41.6 and 76.6. The 4 most informative
      loci were D2S1338, D21S11, D18S51 and FGA. We could select a minimum set of 8
      markers (D2S1338, D21S11, D18S51, FGA, VWA, D19S433, TH01 and D3S1358) that
      provided at least 3 informative loci in 95% of cases. CONCLUSION: This minimum
      STR panel may be an efficient way to detect and quantitate donor-recipient
      chimerism after transplantation.

PMID- 22155343
TI  - A comprehensive survey of maternal plasma miRNAs expression profiles using high
      throughput sequencing.
AB  - OBJECTIVE: Recently, microRNAs (miRNAs) had been shown as potential important
      regulators in pregnancy. Circulating miRNAs are considered as potentially useful
      non-invasive biomarkers for the diagnosis of pregnancy-related disease and
      congenital disorders, but maternal peripheral blood miRNAs expression profile in
      pregnancy remains less investigated. We thus set out to investigate maternal
      plasma miRNAs expression profile using genome-wide sequencing. METHODS: Maternal
      plasma miRNA expression profiles of different pregnancy stages were detected by
      SOLiD sequencing. We observed the expression level of the most abundant miRNAs in
      maternal plasma during pregnancy process. We examined functional relationships of
      targets of pregnancy-relative miRNAs by enrichment analyzing of signaling
      pathways. RESULTS: 147 miRNAs were sequenced from maternal plasma in this study,
      among them, 90 types of miRNAs were found in all of the samples, while 136 miRNAs
      in the first trimester gestation, 108 in second trimester gestation, and 99
      miRNAs in the third trimester gestation, respectively. The varieties and the
      expression level of maternal plasma miRNAs were changing during pregnancy. The
      expression level of miRNA cluster members was changing with the same trend during
      pregnancy. The function and functional relationship analysis of target genes of
      pregnancy-relative miRNAs showed that genetic disorder, immunological disease,
      cell signaling, cancer, and cell cycle were the enriched pathways. CONCLUSIONS:
      Maternal plasma miRNA expression profiles are dynamically changing during
      pregnancy. The results of function analysis suggested that miRNAs may play an
      important role in regulating pregnancy process, which can help us understand the
      refine regulation mechanism in pregnancy. Moreover, the results of this present
      study may be the basis for a further study to find useful prenatal diagnosis
      biomarkers.

PMID- 22155344
TI  - Correlation between enzyme immunoassay and indirect immunofluorescence test for
      high titer of anti-ribosomal-P antibodies.

PMID- 22155345
TI  - Identification of a novel mutation in the ANGPTL3 gene in two families diagnosed
      of familial hypobetalipoproteinemia without APOB mutation.
AB  - BACKGROUND: Familial hypobetalipoproteinemia (FHBL), characterized by extremely
      low levels of plasma apolipoprotein (apo) B and cholesterol associated with low
      density lipoproteins (LDLc), is considered to be an autosomal co-dominant
      disorder of heterogeneous origin. The main genetic disorder associated with FHBL
      consists of mutations in the APOB gene, while other less frequent forms are
      associated with mutations in NPC1L1, PCSK9, a still unidentified gene in 3p21.1
      22 and, more recently, in ANGPTL3. METHODS: We scanned for ANGPTL3 mutations in 4
      unrelated Spanish families with FHBL criteria but negative for mutations in APOB.
      The entire coding region and intron-exon boundaries of the ANGPTL3 gene were
      amplified and sequenced. RESULTS: Two probands were positive for the same
      frameshift mutation, a deletion of 5 bp in codon 121 in ANGPTL3, which produces a
      truncated protein of 122 residues. This mutation in homozygosis was associated in
      both families with combined hypolipidemia, characterized by low plasma apoB, low
      total, LDL and HDL cholesterol and low triglycerides. CONCLUSION: We confirm the
      existence of a new phenotype of FHBL, denominated familial combined
      hypolipidemia, which consist of a biochemical phenotype of low LDLc, low apoB,
      low TG and, unlike APOB mutations, low HDL cholesterol, due to a loss-of-function
      mutation in ANGPTL3.

PMID- 22155346
TI  - Opposite effects of arsenic trioxide on the Nrf2 pathway in oral squamous cell
      carcinoma in vitro and in vivo.
AB  - Nuclear factor erythroid derived 2 like 2 (Nrf2) is a critical transcriptional
      factor in mediating cellular defense mechanisms against oxidative stress or
      electrophiles. Arsenic has been reported to induce malignant transformation of
      human cells through Nrf2-dependent signaling pathway. However, arsenic is also a
      promising cancer therapeutic drug for solid tumors, including oral squamous cell
      carcinoma (OSCC). It is still unclear how Nrf2 may mediate cellular response of
      OSCC cells when treated with arsenic. In order to fully understand the impact of
      arsenic on Nrf2 signaling in human OSCC, we examined expression of Nrf2 and Nrf2
      regulated genes in arsenic trioxide (ATO)-treated OSCC cells in vitro and in ATO
      treated OSCC xenografts. ATO had anti-cancer effects on both cultured OSCC cells
      and OSCC xenografts by inhibiting cell growth, suppressing angiogenesis and
      inducing apoptosis. ATO activated a silent Nrf2 pathway in cultured OSCC cells as
      shown by induction of Nrf2 and Nrf2-regulated genes, NAD(P)H:quinone
      oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), in a dose-dependent manner.
      On the contrary, Nrf2 pathway became active in OSCC xenograft tumors, and ATO
      treatment down-regulated expression of Nrf2 and Nrf2-regulated genes. Our study
      clearly demonstrated opposite effects of ATO on Nrf2 pathway in OSCC cells in
      vitro and in vivo.

PMID- 22155347
TI  - New insights into the roles of ATM and DNA-PKcs in the cellular response to
      oxidative stress.
AB  - Reactive oxygen species (ROS) are induced by a variety of endogenous and
      exogenous sources. At pathologically high levels, ROS cause damage to biological
      molecules, including DNA. The damage sustained by DNA likely plays a key role in
      the pathogenesis of aging and carcinogenesis. Extensive research has established
      in detail the mechanism of cellular response to oxidative stress. Attention is
      now focused on identifying the molecular contributions of the key DNA damage
      response kinases ataxia telangiectasia mutated (ATM), DNA-dependent protein
      kinase catalytic subunit (DNA-PKcs), and ATM- and Rad3-related (ATR) in the
      oxidative stress response. In this review, we will provide an update of the
      current evidence regarding the involvement of these related DNA damage response
      kinases in oxidative DNA lesion repair and signaling responses. The growing
      understanding of the involvement of ATM, DNA-PKcs, and ATR in the oxidative
      stress response will offer new possibilities for the treatment of ROS-related
      diseases.

PMID- 22155348
TI  - Chrysin protects against cisplatin-induced colon. toxicity via amelioration of
      oxidative stress and apoptosis: probable role of p38MAPK and p53.
AB  - Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against
      numerous forms of cancer but it has pronounced adverse effects viz.,
      nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked
      toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone),
      a natural flavone commonly found in many plants possesses multiple biological
      activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In
      the present study, we investigated the protective effect of chrysin against CDDP
      induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity
      and damage includes oxidative stress, activation of p38MAPK and p53, and colonic
      epithelial cell apoptosis via upregulating the expression of Bak and cleaved
      caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive
      days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a
      single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg
      body weight and animals were euthanized after 24 h of cisplatin injection.
      Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity,
      glutathione depletion, decrease in antioxidant (catalase, glutathione reductase,
      glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II
      detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities.
      Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK
      and p53, and apoptotic tissue damage which were induced by CDDP. Histological
      findings further supported the protective effects of chrysin against CDDP-induced
      colonic damage. The results of the present study suggest that the protective
      effect of chrysin against CDDP-induced colon toxicity was related with
      attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic
      tissue damage.

PMID- 22155349
TI  - Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia
      following 7 and 90days of exposure to hexavalent chromium in drinking water.
AB  - Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium
      dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further
      elucidate key events underlying tumor formation, a 90-day drinking water study
      was conducted in B6C3F1 mice. Differential gene expression was examined in
      duodenal and jejunal epithelial samples following 7 or 90days of exposure to 0,
      0.3, 4, 14, 60, 170 or 520mg/L SDD in drinking water. Genome-wide microarray
      analyses identified 6562 duodenal and 4448 jejunal unique differentially
      expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the
      duodenum and jejunum at day 91. Comparative analysis identified significant
      overlap in duodenal and jejunal differential gene expression. Automated dose
      response modeling identified >80% of the differentially expressed genes exhibited
      sigmoidal dose-response curves with EC(50) values ranging from 10 to 100mg/L SDD.
      Only 16 genes satisfying the dose-dependent differential expression criteria had
      EC(50) values <10mg/L SDD, 3 of which were regulated by Nrf2, suggesting
      oxidative stress in response to SDD at low concentrations. Analyses of
      differentially expressed genes identified over-represented functions associated
      with oxidative stress, cell cycle, lipid metabolism, and immune responses
      consistent with the reported effects on redox status and histopathology at
      corresponding SDD drinking water concentrations. Collectively, these data are
      consistent with a mode of action involving oxidative stress and cytotoxicity as
      early key events. This suggests that the tumorigenic effects of chronic Cr(VI)
      oral exposure likely require chronic tissue damage and compensatory epithelial
      cell proliferation.

PMID- 22155350
TI  - Identification of dual mTORC1 and mTORC2 inhibitors in melanoma cells:
      prodigiosin vs. obatoclax.
AB  - The PI3K/AKT/mTOR signaling pathway regulates cell proliferation, survival and
      angiogenesis. The mammalian target of rapamycin (mTOR) is a protein kinase
      ubiquitously expressed within cells that regulates cell growth and survival by
      integrating nutrient and hormonal signals. mTOR exists in two complexes, mTORC1
      and mTORC2. Hyperactivation of the mTOR protein has been linked to development of
      cancer, raising mTOR as an attractive target for cancer therapy. Prodigiosin (PG)
      and obatoclax (OBX), two members of the prodiginines family, are small molecules
      with anticancer properties which are currently under clinical trials. In the
      present paper, we demonstrate that mTOR is a molecular target of both
      prodiginines in melanoma, a highly drug-resistant cancer model. The inhibition of
      mTORC1 and mTORC2 complexes by PG or OBX resulted in a loss of AKT
      phosphorylation at S473, preventing its full activation, with no significant
      effect on T308. The strongest activity inhibition (89%) was induced by PG on
      mTORC2. Binding assays using Surface Plasmon Resonance (SPR) provide kinetic and
      affinity data of the interaction of these small molecules with mTOR. In addition,
      in silico modeling produced a detailed atomic description of the binding modes.
      These results provide new data to understand the mechanism of action of these
      molecules, and provide new structural data that will allow the development of
      more specific mTOR inhibitors for cancer treatment.

PMID- 22155351
TI  - Spatial network structure and metapopulation persistence.
AB  - We explore the relationship between network structure and dynamics by relating
      the topology of spatial networks with its underlying metapopulation abundance.
      Metapopulation abundance is largely affected by the architecture of the spatial
      network, although this effect depends on demographic parameters here represented
      by the extinction-to-colonization ratio (e/c). Thus, for moderate to large e/c
      values, regional abundance grows with the heterogeneity of the network, with
      uniform or random networks having the lowest regional abundances, and scale-free
      networks having the largest abundance. However, the ranking is reversed for low
      extinction probabilities, with heterogeneous networks showing the lowest relative
      abundance. We further explore the mechanisms underlying such results by relating
      a node's incidence (average number of time steps the node is occupied) with its
      degree, and with the average degree of the nodes it interacts with. These results
      demonstrate the importance of spatial network structure to understanding
      metapopulation abundance, and serve to determine under what circumstances
      information on network structure should be complemented with information on the
      species life-history traits to understand persistence in heterogeneous
      environments.

PMID- 22155352
TI  - A simple and sensitive method for lipoprotein and lipids profiles analysis of
      individual micro-liter scale serum samples.
AB  - A simple and sensitive method to determine lipoprotein and lipids profiles in
      micro-liter scale individual serum sample is not presently available. Traditional
      lipoprotein separation techniques either by ultra-centrifugation or by liquid
      chromatography methods have their disadvantages in both lipoprotein separation
      and lipids component quantification. In this study we used small volume needing
      size-exclusion fast protein liquid chromatography to separate different
      lipoprotein subclasses in 50MUL serum. And lipids contents, such as cholesterol,
      cholesterol ester and triacylglycerol, were measured by using two different
      fluorescence-based lipid detection methods. With this method, very low density
      lipoprotein, low density lipoprotein and high density lipoprotein could be easily
      separated, and follow-up lipid detection was completed by simple kinds of
      reactions. Serum lipoprotein and lipids profiling from C57BL/6 mice (n=5) and
      human (n=5) were analyzed. The elution profiles of five individuals were highly
      reproducible, and there were lipoprotein and lipids distribution variations
      between C57BL/6 mice and human beings. In conclusion, this method which combined
      small volume needing size-exclusion fast protein liquid chromatography and
      fluorescence-based lipids measurement, provided a simple, efficient, integrity
      and reproducible procedure for determining serum lipoprotein and lipids profiles
      in micro-liter scale levels. It becomes possible that determination of
      lipoprotein profiles and gaining information of lipids in different lipoproteins
      can be accomplished simultaneously.

PMID- 22155353
TI  - Immunostimulatory effects of gold nanorod and silica-coated gold nanorod on RAW
      264.7 mouse macrophages.
AB  - In this study, we have investigated immunostimulatory effects of gold nanorod
      (Au) and silica-coated gold nanorod (SiAu) concerned with inflammatory mediators
      such as calcium (Ca), hydrogen peroxide, nitric oxide (NO), various cytokines,
      prostaglandin E2 (PGE2), transcription factors, and immune response gene in RAW
      264.7 mouse macrophages. Both Au and SiAu significantly increased the release of
      Ca, hydrogen peroxide, NO, IL-1alpha, IL-1beta, IL-6, IL-10, IP-10, MCP-1, MCP-3,
      TNF-alpha, RANTES, G-CSF, GM-CSF, LIF, MIP-2, VEGF, and PGE2 with enhancing
      expression of STAT1, STAT3, c-Fos, and COX-2 mRNA in RAW 264.7 cells. The results
      suggest that Au and SiAu have immunostimulatory properties to strengthen immune
      reactions via calcium-transcription factors pathway in macrophage.

PMID- 22155354
TI  - Multidrug resistance protein (MRP) 4 attenuates benzo[a]pyrene-mediated DNA
      adduct formation in human bronchoalveolar H358 cells.
AB  - Multi-drug resistance protein (MRP) 4, an ATP-binding cassette (ABC) transporter,
      has broad substrate specificity. It facilitates the transport of bile salt
      conjugates, conjugated steroids, nucleoside analogs, eicosanoids, and
      cardiovascular drugs. Recent studies in liver carcinoma cells and hepatocytes
      showed that MRP4 expression is regulated by the aryl hydrocarbon receptor (AhR)
      and nuclear factor E2-related factor 2 (Nrf2). The AhR has particular importance
      in the lung and is most commonly associated with the up-regulation of cytochrome
      P-450 (CYP)-mediated metabolism of benzo[a]pyrene (B[a]P) to reactive
      intermediates. Treatment of H358, human bronchoalveolar, cells with 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) or (-)-benzo[a]pyrene-7,8-dihydro-7,8-diol
      (B[a]P-7,8-dihydrodiol), the proximate carcinogen of B[a]P, revealed that MRP4
      expression was increased compared to control. This suggested that MRP4 expression
      might contribute to the paradoxical decrease in (+)-7,8-dihydroxy-9,10-epoxy
      7,8,9,10-tetrahydrobenzo[a]pyrene-2'-deoxyguanosine ((+)-anti-trans-B[a]PDE-dGuo)
      DNA-adducts observed in TCDD-treated H358 cells. We have now found that decreased
      MRP4 expression induced by a short hairpin RNA (shRNA), or chemical inhibition
      with probenecid, increased (+)-anti-trans-B[a]PDE-dGuo formation in cells treated
      with (-)-B[a]P-7,8-dihydrodiol, but not the ultimate carcinogen (+)-anti-trans
      B[a]PDE. Thus, up-regulation of MRP4 increased cellular efflux of (-)-B[a]P-7,8
      dihydrodiol, which attenuated DNA-adduct formation. This is the first report
      identifying a specific MRP efflux transporter that decreases DNA damage arising
      from an environmental carcinogen.

PMID- 22155355
TI  - Simultaneous determination of nicotine and PAH metabolites in human hair
      specimen: a potential methodology to assess tobacco smoke contribution in PAH
      exposure.
AB  - The present methodology was developed to simultaneously assess chronic exposure
      to PAHs and to tobacco from the analysis of one hair specimen per examined
      individual. The method is a two step extraction of twelve mono-hydroxy-PAHs and
      of nicotine, and their separate analysis by optimized methods using gas
      chromatography-negative chemical ionization-mass spectrometry. After method
      validation and assessment of the hair decontamination procedure, 105 hair
      specimens from smokers and non-smokers were analyzed. All the hair samples tested
      positive for nicotine. Median concentration was 10.7ng/mg for smokers and
      0.5ng/mg for non-smokers. 70% of the samples tested positive for OH-PAHs. The
      most common one was 2-naphthol (61%) and its concentration was significantly
      higher in smokers than in non-smokers (median: 111 vs 70pmol/g, p=0.006). 2-OH
      benzo(c)phenanthrene and 6-OH-chrysene were only detected once in a non-smoker's
      hair. The concentration of the sum of all PAH-metabolites ranged from 24 to
      67190pmol/g (median: 118pmol/g). Only six samples tested positive for more than
      two different metabolites. The simultaneous detection of nicotine and OH-PAHs in
      hair is possible and provides reliable results. This represents a useful tool for
      the accurate biomonitoring of chronic exposure to PAH and correct identification
      of the sources of exposure.

PMID- 22155356
TI  - Urinary metabolites as biomarkers of human exposure to atrazine: atrazine
      mercapturate in agricultural workers.
AB  - Human exposure to atrazine and other triazine herbicides results in urinary
      excretion of traces of parent compounds and of their metabolites formed by N
      dealkylation or conjugation with mercapturic acid. In contrast to N-dealkylated
      metabolites, which are not compound-specific, the measurement of atrazine
      mercapturate and unchanged atrazine provides an unambiguous confirmation of
      exposure to this herbicide. The aim of this study was to investigate the levels
      of these two compounds in a group of agricultural workers who may be considered
      representative for typical behaviour and procedures during the atrazine
      application in Croatia. The spot urine samples were collected at the beginning
      (samples A) and at the end (samples B) of a working day and 12h after exposure
      has ended (samples C). Atrazine and atrazine mercapturate were extracted from
      acidified urine samples (pH 2) with ethyl acetate and the extracts were analysed
      using high performance liquid chromatography-tandem mass spectrometry with a
      turbo ion spray (electrospray) ionization interface. The detection limits based
      on treatment of 2ml urine samples were 0.2ngml(-1) for both analytes. Atrazine
      was not detected in any of 27 analysed urine samples but traces of atrazine
      mercapturate were measured in about a third of pre-exposure and in all post
      exposure urine samples in mass concentrations ranging from 0.3 to 10.4ngml(-1)
      (0.3 to 8.0MUgg(-1) of creatinine). The metabolite concentrations in B and C
      group of post-exposure samples were not significantly different. The urinary
      atrazine mercapturate post-exposure concentrations were comparable to those
      reported for U.S. farmers engaged in a single field application of atrazine.

PMID- 22155357
TI  - CYP2S1 is negatively regulated by corticosteroids in human cell lines.
AB  - Cytochrome P450s are monooxygenase proteins involved in the metabolism of both
      exogenous and endogenous compounds. CYP2S1 can metabolize eicosanoids in the
      absence of both NADPH and NADPH cytochrome P450 reductase, and can also activate
      the anticancer agent 1 AQ4N [1,4-bis{[2-(dimethylamino-N-oxide)ethyl]amino}-5,8
      dihydroxy anthracene-9,10-dione]. CYP2S1 is mainly expressed in extrahepatic
      tissues such as the trachea, lung, stomach, small intestine, spleen, skin,
      breast, kidney and placenta. Furthermore, increased expression of CYP2S1 occurs
      in several tumors of epithelial origin, making the characterization of CYP2S1
      regulation relevant to the treatment of disease. We report that the synthetic
      glucocorticoid receptor ligand dexamethasone (DEX) represses CYP2S1 expression.
      The ED(50) is between 1 nM and 3 nM and maximal repression is reached by 48 h.
      Other corticosteroids are also effective at repressing CYP2S1. We show that
      repression by DEX is mediated by the glucocorticoid receptor and requires histone
      deacetylase activity.

PMID- 22155358
TI  - Functional bias of positively selected genes in Streptococcus genomes.
AB  - Rates of nonsynonymous substitution (dN) significantly higher than rates of
      synonymous substitution (dS) have been used as evidence of positive selection for
      the fixation of advantageous point mutations. It has been suggested that positive
      selection contributes to the evolution of virulence factors and certain
      functional categories in bacterial pathogens. The genus Streptococcus contains a
      number of important human and agricultural pathogens. Here we assessed positive
      selection across 13 Streptococcus species, and their relationship with virulence
      factors and functional categories. We found that known virulence genes were
      subject to positive selection pressure as much as other genes. After false
      discovery rate correction for multiple comparisons, no functional categories were
      significantly over- or under-represented in positively selected genes relative to
      other genes. Our results suggest that within the genus Streptococcus positive
      selection based on dN/dS ratios is not distributed with bias across biological
      functions.

PMID- 22155359
TI  - The internal transcribed spacer of ribosomal RNA genes in plant trypanosomes
      (Phytomonas spp.) resolves 10 groups.
AB  - The distinction between plant trypanosomatids and opportunistic monoxenous insect
      trypanosomatids has not been demarcated clearly due to the mass placement of all
      trypanosomatids isolated from plants into the arbitrary genus Phytomonas spp. The
      advent of molecular markers has been useful in distinguishing plant
      trypanosomatids from the rest of the Trypanosomatidae family. Here we have
      examined the internal transcribed spacer (ITS) region of the ribosomal RNA (rRNA)
      locus for classification purposes. This region contains two distinct ITSs flanked
      by the small subunit and large subunit of ribosomal RNA genes and separated by
      the 5.8S ribosomal RNA gene. Sequences within the 5.8S ribosomal RNA gene and in
      the ITS sequences can serve as specific markers for several of the Phytomonas
      groups. Microsatellite sequences were identified in Phytomonas spp. in both ITS
      regions. Several classes of microsatellites were seen, with inter-isolate
      variation that has potential for future use. Maximum Likelihood analysis of the
      ITS sequences of 20 Phytomonas isolates representing the eight defined groups and
      a few unclassified isolates revealed a total of 10 distinct subgroups within our
      collection, of which two are new. The ITS region, which includes the 5.8S
      sequence, is a robust marker for the subdivisions within the genus Phytomonas
      spp.

PMID- 22155360
TI  - A phylogeny of the northern temperate leafy liverwort genus Scapania
      (Scapaniaceae, Jungermanniales).
AB  - Scapania is a northern temperate genus with a few disjunctions in the south.
      Despite receiving considerable attention, the supraspecific classification of
      this genus remains unsatisfactorily solved. We use three molecular markers
      (nrITS, cpDNA trnL-F region, atpB-rbcL spacer) and 175 accessions belonging to 50
      species (plus eight outgroup taxa) to estimate the phylogeny and to test current
      classification systems. Our data support the classification of Scapania into six
      rather than three subgenera, rearrangements within numerous sections, and
      inclusion of Macrodiplophyllum microdontum. Scapania species with a plicate
      perianth form three early diverging lineages; the most speciose subgenus,
      Scapania s.str., represents a derived clade. Most morphological species concepts
      are supported by the molecular topologies but classification of sect. Curtae
      requires further study. Southern lineages are nested in northern hemispheric
      clades. Palearctic-Nearctic distribution ranges are supported for several
      species.

PMID- 22155361
TI  - Comparative psychology and the grand challenge of drug discovery in psychiatry
      and neurodegeneration.
AB  - Drug discovery for brain disorders is undergoing a period of upheaval. Faced with
      an empty drug pipeline and numerous failures of potential new drugs in clinical
      trials, many large pharmaceutical companies have been shrinking or even closing
      down their research divisions that focus on central nervous system (CNS)
      disorders. In this paper, we argue that many of the difficulties facing CNS drug
      discovery stem from a lack of robustness in pre-clinical (i.e., non-human animal)
      testing. There are two main sources for this lack of robustness. First, there is
      the lack of replicability of many results from the pre-clinical stage, which we
      argue is driven by a combination of publication bias and inappropriate selection
      of statistical and experimental designs. Second, there is the frequent failure to
      translate results in non-human animals to parallel results in humans in the
      clinic. This limitation can only be overcome by developing new behavioral tests
      for non-human animals that have predictive, construct, and etiological validity.
      Here, we present these translational difficulties as a "grand challenge" to
      researchers from comparative cognition, who are well positioned to provide new
      methods for testing behavior and cognition in non-human animals. These new
      experimental protocols will need to be both statistically robust and target
      behavioral and cognitive processes that allow for better connection with human
      CNS disorders. Our hope is that this downturn in industrial research may
      represent an opportunity to develop new protocols that will re-kindle the search
      for more effective and safer drugs for CNS disorders.

PMID- 22155362
TI  - Comparative cognition: function and mechanism in lab and field. A tribute to the
      contributions of Alex Kacelnik.

PMID- 22155363
TI  - Modeling the emergence of HIV-1 drug resistance resulting from antiretroviral
      therapy: insights from theoretical and numerical studies.
AB  - The use of antiretroviral therapy has proven to be remarkably effective in
      controlling the progression of human immunodeficiency virus (HIV) infection and
      prolonging patient's survival. Therapy however may fail and therefore these
      benefits can be compromised by the emergence of HIV strains that are resistant to
      the therapy. In view of these facts, the question of finding the reason for which
      drug-resistant strains emerge during therapy has become a worldwide problem of
      great interest. This paper presents a deterministic HIV-1 model to examine the
      mechanisms underlying the emergence of drug-resistance during therapy. The aim of
      this study is to determine whether, and how fast, antiretroviral therapy may
      determine the emergence of drug resistance by calculating the basic reproductive
      numbers. The existence, feasibility and local stability of the equilibriums are
      also analyzed. By performing numerical simulations we show that Hopf bifurcation
      may occur. The model suggests that the individuals with drug-resistant infection
      may play an important role in the epidemic of HIV.

PMID- 22155364
TI  - Peptidomimetic escape mechanisms arise via genetic diversity in the ligand
      binding site of the hepatitis C virus NS3/4A serine protease.
AB  - BACKGROUND & AIMS: It is a challenge to develop direct-acting antiviral agents
      that target the nonstructural protein 3/4A protease of hepatitis C virus because
      resistant variants develop. Ketoamide compounds, designed to mimic the natural
      protease substrate, have been developed as inhibitors. However, clinical trials
      have revealed rapid selection of resistant mutants, most of which are considered
      to be pre-existing variants. METHODS: We identified residues near the ketoamide
      binding site in x-ray structures of the genotype 1a protease, co-crystallized
      with boceprevir or a telaprevir-like ligand, and then identified variants at
      these positions in 219 genotype-1 sequences from a public database. We used side
      chain modeling to assess the potential effects of these variants on the
      interaction between ketoamide and the protease, and compared these results with
      the phenotypic effects on ketoamide resistance, RNA replication capacity, and
      infectious virus yields in a cell culture model of infection. RESULTS: Thirteen
      natural binding-site variants with potential for ketoamide resistance were
      identified at 10 residues in the protease, near the ketoamide binding site.
      Rotamer analysis of amino acid side-chain conformations indicated that 2 variants
      (R155K and D168G) could affect binding of telaprevir more than boceprevir.
      Measurements of antiviral susceptibility in cell-culture studies were consistent
      with this observation. Four variants (ie, Q41H, I132V, R155K, and D168G) caused
      low-to-moderate levels of ketoamide resistance; 3 of these were highly fit (Q41H,
      I132V, and R155K). CONCLUSIONS: Using a comprehensive sequence and structure
      based analysis, we showed how natural variation in the hepatitis C virus protease
      nonstructural protein 3/4A sequences might affect susceptibility to first
      generation direct-acting antiviral agents. These findings increase our
      understanding of the molecular basis of ketoamide resistance among naturally
      existing viral variants.

PMID- 22155365
TI  - Autophagy protects cells from HCV-induced defects in lipid metabolism.
AB  - BACKGROUND & AIMS: Autophagy is a lysosome-mediated catabolic process that
      mediates degradation and recycling of all major components of eukaryotic cells.
      Different stresses, including viral and bacterial infection, induce autophagy,
      which can promote cell survival by removing the stress inducer or by attenuating
      its dangerous effects. High levels of autophagy occur during infection of cells
      with hepatitis C virus (HCV), but the clinical relevance of this process is not
      clear. METHODS: Levels of autophagy were analyzed in liver biopsy samples from 22
      patients with HCV infection using microtubule-associated protein-1 light chain 3
      immunoblotting; associations with histological and metabolic parameters were
      evaluated by Pearson correlation analysis. We investigated the role of HCV
      induced autophagy in lipid degradation in cells infected with the virus or
      replicons, and analyzed autophagosome contents by confocal microscopy and by
      measuring lipid levels after inhibition of autophagy by Beclin 1 knockdown or
      lysosome inhibitors. RESULTS: In liver biopsy samples from patients with HCV,
      there was an inverse correlation between microvesicular steatosis and level of
      autophagy (r = -0.617; P = .002). HCV selectively induced autophagy of lipids in
      virus-infected and replicon cells. In each system, autophagosomes frequently
      colocalized with lipid deposits, mainly formed by unesterified cholesterol.
      Inhibition of the autophagic process in these cells significantly increased the
      induction of cholesterol accumulation by HCV. CONCLUSIONS: Autophagy counteracts
      the alterations in lipid metabolism induced by HCV. Disruption of the autophagic
      process might contribute to development of steatosis in patients with HCV.

PMID- 22155366
TI  - Inhibition of Cdc25A suppresses hepato-renal cystogenesis in rodent models of
      polycystic kidney and liver disease.
AB  - BACKGROUND & AIMS: In polycystic kidney disease and polycystic liver disease
      (PLD), the normally nonproliferative hepato-renal epithelia acquire a
      proliferative, cystic phenotype that is linked to overexpression of cell division
      cycle 25 (Cdc25)A phosphatase and cell-cycle deregulation. We investigated the
      effects of Cdc25A inhibition in mice and rats via genetic and pharmacologic
      approaches. METHODS: Cdc25A(+/-) mice (which have reduced levels of Cdc25A) were
      cross-bred with polycystic kidney and hepatic disease 1 (Pkhd1(del2/del2)) mice
      (which have increased levels of Cdc25A and develop hepatic cysts). Cdc25A
      expression was analyzed in livers of control and polycystic kidney (PCK) rats,
      control and polycystic kidney 2 (Pkd2(ws25/-)) mice, healthy individuals, and
      patients with PLD. We examined effects of pharmacologic inhibition of Cdc25A with
      vitamin K3 (VK3) on the cell cycle, proliferation, and cyst expansion in vitro;
      hepato-renal cystogenesis in PCK rats and Pkd2(ws25/-)mice; and expression of
      Cdc25A and the cell-cycle proteins regulated by Cdc25A. We also examined the
      effects of the Cdc25A inhibitor PM-20 on hepato-renal cystogenesis in Pkd2(ws25/
      ) mice. RESULTS: Liver weights and hepatic and fibrotic areas were decreased by
      32%-52% in Cdc25A(+/-):Pkhd1(del2/del2) mice, compared with Pkhd1(del2/del2)
      mice. VK3 altered the cell cycle and reduced proliferation of cultured
      cholangiocytes by 32%-83% and decreased growth of cultured cysts by 23%-67%. In
      PCK rats and Pkd2(ws25/-) mice, VK3 reduced liver and kidney weights and hepato
      renal cystic and fibrotic areas by 18%-34%. PM-20 decreased hepato-renal
      cystogenesis in Pkd2(ws25/-) mice by 15%. CONCLUSIONS: Cdc25A inhibitors block
      cell-cycle progression and proliferation, reduce liver and kidney weights and
      cyst growth in animal models of polycystic kidney disease and PLD, and might be
      developed as therapeutics for these diseases.

PMID- 22155367
TI  - Disruption of Klf4 in villin-positive gastric progenitor cells promotes formation
      and progression of tumors of the antrum in mice.
AB  - BACKGROUND & AIMS: Kruppel-like factor 4 (Klf4) is a putative gastric tumor
      suppressor gene. Rare, villin-positive progenitor cells in the gastric antrum
      have multilineage potential. We investigated the function of Klf4 in these cells
      and in gastric carcinogenesis. METHODS: We created mice with disruption of Klf4
      in villin-positive antral mucosa cells (Villin-Cre(+);Klf4(fl/fl) mice). Villin
      Cre(+);Klf4(fl/fl) and control mice were given drinking water with or without 240
      ppm N-methyl-N-nitrosourea at 5 weeks of age and thereafter on alternating weeks
      for a total of 10 weeks. Gastric mucosa samples were collected at 35, 50, or 80
      weeks of age from mice that were and were not given N-methyl-N-nitrosourea, and
      analyzed by histopathologic and molecular analyses. Findings were compared with
      those from human gastric tumor specimens. RESULTS: Preneoplasia formed
      progressively in the antrum in 35- to 80-week-old Villin-Cre(+);Klf4(fl/fl) mice.
      Gastric tumors developed in 29% of 80-week-old Villin-Cre(+);Klf4(fl/fl) mice,
      which were located exclusively in the lesser curvature of the antrum. N-methyl-N
      nitrosourea accelerated tumor formation, and tumors developed significantly more
      frequently in Villin-Cre(+);Klf4(fl/fl) mice than in control mice, at 35 and 50
      weeks of age. Mouse and human gastric tumors had reduced expression of Kruppel
      like factor 4 and increased expression of FoxM1 compared with healthy gastric
      tissue. Expression of Kruppel-like factor 4 suppressed transcription of FoxM1.
      CONCLUSIONS: Inactivation of Klf4 in villin-positive gastric progenitor cells
      induces transformation of the gastric mucosa and tumorigenesis in the antrum in
      mice. Villin-Cre(+);Klf4(fl/fl) have greater susceptibility to chemical-induced
      gastric carcinogenesis and increased rates of gastric tumor progression than
      control mice.

PMID- 22155368
TI  - CLMP is required for intestinal development, and loss-of-function mutations cause
      congenital short-bowel syndrome.
AB  - BACKGROUND & AIMS: Short-bowel syndrome usually results from surgical resection
      of the small intestine for diseases such as intestinal atresias, volvulus, and
      necrotizing enterocolitis. Patients with congenital short-bowel syndrome (CSBS)
      are born with a substantial shortening of the small intestine, to a mean length
      of 50 cm, compared with a normal length at birth of 190-280 cm. They also are
      born with intestinal malrotation. Because CSBS occurs in many consanguineous
      families, it is considered to be an autosomal-recessive disorder. We aimed to
      identify and characterize the genetic factor causing CSBS. METHODS: We performed
      homozygosity mapping using 610,000 K single-nucleotide polymorphism arrays to
      analyze the genomes of 5 patients with CSBS. After identifying a gene causing the
      disease, we determined its expression pattern in human embryos. We also
      overexpressed forms of the gene product that were and were not associated with
      CSBS in Chinese Hamster Ovary and T84 cells and generated a zebrafish model of
      the disease. RESULTS: We identified loss-of-function mutations in Coxsackie- and
      adenovirus receptor-like membrane protein (CLMP) in CSBS patients. CLMP is a
      tight-junction-associated protein that is expressed in the intestine of human
      embryos throughout development. Mutations in CLMP prevented its normal
      localization to the cell membrane. Knock-down experiments in zebrafish resulted
      in general developmental defects, including shortening of the intestine and the
      absence of goblet cells. Because goblet cells are characteristic for the
      midintestine in zebrafish, which resembles the small intestine in human beings,
      the zebrafish model mimics CSBS. CONCLUSIONS: Loss-of-function mutations in CLMP
      cause CSBS in human beings, likely by interfering with tight-junction formation,
      which disrupts intestinal development. Furthermore, we developed a zebrafish
      model of CSBS.

PMID- 22155369
TI  - Fecal transplantation, through colonoscopy, is effective therapy for recurrent
      Clostridium difficile infection.
AB  - BACKGROUND & AIMS: Treatment of recurrent Clostridium difficile infection (CDI)
      with antibiotics leads to recurrences in up to 50% of patients. We investigated
      the efficacy of fecal transplantation in treatment of recurrent CDI. METHODS: We
      reviewed records from 70 patients with recurrent CDI who had undergone fecal
      transplantation. Fecal transplantation was performed at colonoscopy by infusing
      fresh donor feces into cecum. Before transplantation, the patients had whole
      bowel lavage with polyethylene glycol solution. Clinical failure was defined as
      persistent or recurrent symptoms and signs, and a need for new therapy. RESULTS:
      During the first 12 weeks after fecal transplantation, symptoms resolved in all
      patients who did not have strain 027 C difficile infections. Of 36 patients with
      027 C difficile infection, 32 (89%) had a favorable response; all 4 nonresponders
      had a pre-existing serious condition, caused by a long-lasting diarrheal disease
      or comorbidity and subsequently died of colitis. During the first year after
      transplantation, 4 patients with an initial favorable response had a relapse
      after receiving antibiotics for unrelated causes; 2 were treated successfully
      with another fecal transplantation and 2 with antibiotics for CDI. Ten patients
      died of unrelated illnesses within 1 year after transplantation. No immediate
      complications of fecal transplantation were observed. CONCLUSIONS: Fecal
      transplantation through colonoscopy seems to be an effective treatment for
      recurrent CDI and also for recurrent CDI caused by the virulent C difficile 027
      strain.

PMID- 22155370
TI  - Glutamine induces nuclear degradation of the NF-kappaB p65 subunit in Caco-2/TC7
      cells.
AB  - In the intestine, NF-kappaB is the main transcription factor involved in the anti
      inflammatory effect of glutamine and we previously demonstrated that glutamine
      via its conversion to glutamate diminished the p65 protein content in Caco-2/TC7
      cell nuclei without affecting the stimulating effect of IL-1beta on NF-kappaB
      [21]. However, the molecular mechanism by which glutamine acts is not
      established. We therefore tried to identify such a mechanism. Our results
      demonstrate that glutamine decreased the intracellular NF-kappaB through the
      nuclear ubiquitin-proteasome pathway requiring therefore the nuclear
      translocation of the factor. Indeed, time-course study revealed that glutamine
      induced an increase in the nuclear p65 content within the first 15 min of
      culture, the p65 nuclear and cytosolic content decreasing gradually thereafter to
      reach 50 % of the control value after 60 min. This translocation was initiated by
      the phosphorylation of IkappaBalpha by the IKKbeta subunit inducing its
      degradation and the p65 translocation. In parallel, glutamine activated the
      IKKalpha subunit which in turn phosphorylates p65 at Ser 536 which was
      responsible for p65 degradation by the nuclear proteasome. We also demonstrate
      that p38 MAPK lies between glutamine and the NF-kappaB pathway. In conclusion,
      this study identified for the first time the signaling pathway by which glutamine
      may protect against inflammatory conditions.

PMID- 22155371
TI  - Impaired redox signaling and mitochondrial uncoupling contributes vascular
      inflammation and cardiac dysfunction in type 1 diabetes: Protective role of
      arjunolic acid.
AB  - Vascular inflammation and cardiac dysfunction are the leading causes of mortality
      and morbidity among the diabetic patients. Type 1 diabetic mellitus (T1DM) is
      associated with increased cardiovascular complications at an early stage of the
      disease. The purpose of the present study was to explore whether arjunolic acid
      (AA) plays any protective role against cardiovascular complications in T1DM and
      if so, what molecular pathways it utilizes for the mechanism of its protective
      action. Streptozotocin (STZ) was used to induce T1DM in experimental rats.
      Alteration in plasma lipid profile and release of membrane bound enzymes like LDH
      (lactate dehydrogenase) and CK (creatine kinase) established the association of
      hyperlipidemia and cell membrane disintegration with hyperglycemia. Hyperglycemia
      altered the levels of oxidative stress related biomarkers, decreased the
      intracellular NAD and ATP concentrations. Hyperglycemia-induced enhanced levels
      of VEGF, ICAM-1, MCP-1 and IL-6 in the plasma of STZ treated animals indicate
      vascular inflammation in T1DM. Histological studies and FACS analysis revealed
      that hyperglycemia caused cell death mostly via the apoptotic pathway.
      Investigating molecular mechanism, we observed NF-kappaB and MAPKs (p38 and
      ERK1/2) activations, mitochondrial membrane depolarization, cytochrome C release,
      caspase 3 activation and PARP cleavage in apoptotic cell death in the diabetic
      cardiac tissue. Treatment with AA (20 mg/kg body weight) reduced hyperglycemia,
      membrane disintegration, oxidative stress, vascular inflammation and prevented
      the activation of oxidative stress induced signaling cascades leading to cell
      death. Results suggest that AA possesses the potential to be a beneficial
      therapeutic agent in diabetes and its associated cardiac complications.

PMID- 22155372
TI  - A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs
      inward rectification of Kir2.1 currents.
AB  - AIMS: Short-QT syndrome (SQTS) is a recently recognized disorder associated with
      atrial fibrillation (AF) and sudden death due to ventricular arrhythmias.
      Mutations in several ion channel genes have been linked to SQTS; however, the
      mechanism remains unclear. This study describes a novel heterozygous gain-of
      function mutation in the inward rectifier potassium channel gene, KCNJ2,
      identified in SQTS. METHODS AND RESULTS: We studied an 8-year-old girl with a
      markedly short-QT interval (QT = 172 ms, QTc = 194 ms) who suffered from
      paroxysmal AF. Mutational analysis identified a novel heterozygous KCNJ2
      mutation, M301K. Functional assays displayed no Kir2.1 currents when M301K
      channels were expressed alone. However, co-expression of wild-type (WT) with
      M301K resulted in larger outward currents than the WT at more than -30 mV. These
      results suggest a gain-of-function type modulation due to decreased inward
      rectification. Furthermore, we analysed the functional significance of the amino
      acid charge at M301 (neutral) by changing the residue. As with M301K, in M301R
      (positive), the homozygous channels were non-functional, whereas the heterozygous
      channels demonstrated decreased inward rectification. Meanwhile, the currents
      recorded in M301A (neutral) showed normal inward rectification under both homo-
      and heterozygous conditions. Heterozygous overexpression of WT and M301K in
      neonatal rat ventricular myocytes exhibited markedly shorter action potential
      durations than the WT alone. CONCLUSION: In this study, we identified a novel
      KCNJ2 gain-of-function mutation, M301K, associated with SQTS. Functional assays
      revealed no functional currents in the homozygous channels, whereas impaired
      inward rectification demonstrated under the heterozygous condition resulted in
      larger outward currents, which is a novel mechanism predisposing SQTS.

PMID- 22155373
TI  - Resolution of idiopathic recurrent pericarditis in a psoriatic arthritis patient
      treated with etanercept.

PMID- 22155374
TI  - Effects of normal aging on event-related potentials and oscillatory brain
      activity during a haptic repetition priming task.
AB  - This study reports neural repetition effects in young and older adults while
      performing a haptic repetition priming task consisting in the detection of the
      bilateral symmetry of familiar objects. To examine changes in event-related
      potentials (ERPs) and induced brain oscillations of object repetition priming
      with aging, we recorded EEGs of healthy groups of young (n=14; mean age=29.93
      years) and older adults (n=15; mean age=66.4). Both groups exhibited similar
      behavioral haptic priming across repetitions, although young adults responded
      faster than the older group. Young and older adults showed ERP repetition
      enhancement at the 500-900 ms time window. In contrast, only the young
      participants showed ERP repetition suppression at the 1200-1500 ms segment. The
      results from the induced oscillations showed more positive amplitudes in young
      than in older adults at theta, alpha and beta frequencies (4-30 Hz). In addition,
      we found amplitude modulation related to stimulus repetition in the upper alpha
      and low beta sub-bands only in young adults (1250-1750 ms).The results suggest
      that although behavioral priming is spared with age, normal aging affects ERPs
      and oscillatory responses when performing an incidental priming symmetry
      detection task with haptically explored objects.

PMID- 22155375
TI  - Age-related adaptations of brain function during a memory task are also present
      at rest.
AB  - Several studies have demonstrated age-related regional differences in the
      magnitude of the BOLD signal using task-based fMRI. It has been suggested that
      functional changes reflect either compensatory or de-differentiation mechanisms,
      both of which assume response to a specific stimulus. Here, we have tested
      whether ageing affects both task-based and resting brain function, and the extent
      to which functional changes are mediated by reductions in grey matter (GM)
      volume. Two groups, of 22 healthy younger and 22 older volunteers, underwent an
      imaging protocol involving structural and functional MRI, both during a memory
      task and at rest. The two groups had similar socio-demographical characteristics
      and cognitive performance. Image analysis revealed both structural and functional
      differences. Increased BOLD signal in older relative to younger volunteers was
      mainly observed in the frontal lobes, both during the task and at rest.
      Functional changes in the frontal lobes were largely located in brain regions
      spared from GM loss, and adding GM covariates to the fMRI analysis did not
      significantly alter the group differences. Our results are consistent with the
      suggestion that, during normal ageing, the brain responds to neuronal loss by
      fine-tuning connections between spared neurons. Longitudinal studies will be
      necessary to fully test this hypothesis.

PMID- 22155377
TI  - Automatic hippocampal segmentation in temporal lobe epilepsy: impact of
      developmental abnormalities.
AB  - In drug-resistant temporal lobe epilepsy (TLE), detecting hippocampal atrophy on
      MRI is important as it allows defining the surgical target. The performance of
      automatic segmentation in TLE has so far been considered unsatisfactory. In
      addition to atrophy, about 40% of patients present with developmental
      abnormalities (referred to as malrotation) characterized by atypical morphologies
      of the hippocampus and collateral sulcus. Our purpose was to evaluate the impact
      of malrotation and atrophy on the performance of three state-of-the-art automated
      algorithms. We segmented the hippocampus in 66 patients and 35 sex- and age
      matched healthy subjects using a region-growing algorithm constrained by
      anatomical priors (SACHA), a freely available atlas-based software (FreeSurfer)
      and a multi-atlas approach (ANIMAL-multi). To quantify malrotation, we generated
      3D models from manual hippocampal labels and automatically extracted collateral
      sulci. The accuracy of automated techniques was evaluated relative to manual
      labeling using the Dice similarity index and surface-based shape mapping, for
      which we computed vertex-wise displacement vectors between automated and manual
      segmentations. We then correlated segmentation accuracy with malrotation features
      and atrophy. ANIMAL-multi demonstrated similar accuracy in patients and healthy
      controls (p > 0.1), whereas SACHA and FreeSurfer were less accurate in patients
      (p < 0.05). Surface-based analysis of contour accuracy revealed that SACHA over
      estimated the lateral border of malrotated hippocampi (r = 0.61; p < 0.0001), but
      performed well in the presence of atrophy (|r |< 0.34; p > 0.2). Conversely,
      FreeSurfer and ANIMAL-multi were affected by both malrotation (FreeSurfer: r =
      0.57; p = 0.02, ANIMAL-multi: r = 0.50; p = 0.05) and atrophy (FreeSurfer: r =
      0.78, p < 0.0001, ANIMAL-multi: r = 0.61; p < 0.0001). Compared to manual
      volumetry, automated procedures underestimated the magnitude of atrophy (Cohen's
      d: manual: 1.68; ANIMAL-multi: 1.11; SACHA: 1.10; FreeSurfer: 0.90, p < 0.0001).
      In addition, they tended to lateralize the seizure focus less accurately in the
      presence of malrotation (manual: 64%; ANIMAL-multi: 55%, p = 0.4; SACHA: 50%, p =
      0.1; FreeSurfer: 41%, p = 0.05). Hippocampal developmental anomalies and atrophy
      had a negative impact on the segmentation performance of three state-of-the-art
      automated methods. These shape variants should be taken into account when
      designing segmentation algorithms.

PMID- 22155376
TI  - fMRI-DTI modeling via landmark distance atlases for prediction and detection of
      fiber tracts.
AB  - The overall goal of this research is the design of statistical atlas models that
      can be created from normal subjects, but may generalize to be applicable to
      abnormal brains. We present a new style of joint modeling of fMRI, DTI, and
      structural MRI. Motivated by the fact that a white matter tract and related
      cortical areas are likely to displace together in the presence of a mass lesion
      (brain tumor), in this work we propose a rotation and translation invariant model
      that represents the spatial relationship between fiber tracts and anatomic and
      functional landmarks. This landmark distance model provides a new basis for
      representation of fiber tracts and can be used for detection and prediction of
      fiber tracts based on landmarks. Our results indicate that the measured model is
      consistent across normal subjects, and thus suitable for atlas building. Our
      experiments demonstrate that the model is robust to displacement and missing
      data, and can be successfully applied to a small group of patients with mass
      lesions.

PMID- 22155378
TI  - Patterns of hemodynamic low-frequency oscillations in the brain are modulated by
      the nature of free thought during rest.
AB  - During conscious rest, the mind switches into a state of wandering. Although this
      rich inner experience occupies a large portion of the time spent awake, how it
      relates to brain activity has not been well explored. Here, we report the results
      of a behavioral and functional magnetic resonance imaging (fMRI) study of the
      continuous resting state in 307 healthy participants. The analysis focused on the
      relationship between the nature of inner experience and the temporal correlations
      computed between the low-frequency blood oxygen level-dependent (BOLD)
      fluctuations (0.01-0.1 Hz) of five large-scale modules. The subjects' self
      reported time spontaneously spent on visual mental imagery and/or inner language
      was used as the behavioral variable. Decreased temporal correlations between
      modules were revealed when subjects reported more time spent thinking in mental
      images and inner language. These changes segregated the three modules supporting
      inner-oriented activities from those associated with sensory-related and
      externally guided activities. Among the brain areas associated with inner
      oriented processing, the module including the lateral parietal and frontal
      regions (commonly described as being engaged in the manipulation and maintenance
      of internal information) was implicated in the majority of these effects. The
      preponderance of segregation appears to be the signature of the spontaneous
      sequence of thoughts during rest that are not constrained by logic, causality, or
      even a rigorous temporal organization. In other words, though goal-directed tasks
      have been demonstrated to rely on specific regional integration, mind wandering
      can be characterized by widespread modular segregation. Overall, the present
      study provides evidence that modulation of spontaneous low-frequency fluctuations
      in the brain is at least partially explained by spontaneous conscious cognition
      while at rest.

PMID- 22155379
TI  - Time course of ERP generators to syllables in infants: a source localization
      study using age-appropriate brain templates.
AB  - Event-related potentials (ERPs) have become an important tool in the quest to
      understand how infants process perceptual information. Identification of the
      activation loci of the ERP generators is a technique that provides an opportunity
      to explore the neural substrates that underlie auditory processing. Nevertheless,
      as infant brain templates from healthy, non-clinical samples have not been
      available, the majority of source localization studies in infants have used non
      realistic head models, or brain templates derived from older children or adults.
      Given the dramatic structural changes seen across infancy, all of which
      profoundly affect the electrical fields measured with EEG, it is important to use
      individual MRIs or age-appropriate brain templates and parameters to explore the
      localization and time course of auditory ERP sources. In this study 6-month-old
      infants were presented with a passive oddball paradigm using consonant-vowel (CV)
      syllables that differed in voice onset time. Dense-array EEG/ERPs were collected
      while the infants were awake and alert. In addition, MRIs were acquired during
      natural non-sedated sleep for a subset of the sample. Discrete dipole and
      distributed source models were mapped onto individual and averaged infant MRIs.
      The CV syllables elicited a positive deflection at about 200 ms followed by a
      negative deflection that peaked around 400 ms. The source models generated placed
      the dipoles at temporal areas close to auditory cortex for both positive and
      negative responses. Notably, an additional dipole for the positive peak was
      localized at the frontal area, at the anterior cingulate cortex (ACC) level. ACC
      activation has been reported in adults, but has not, to date, been reported in
      infants during processing of speech-related signals. The frontal ACC activation
      was earlier but smaller in amplitude than the left and right auditory temporal
      activations. These results demonstrate that in infancy the ERP generators to CV
      syllables are localized in cortical areas similar to that reported in adults, but
      exhibit a notably different temporal course. Specifically, ACC activation in
      infants significantly precedes auditory temporal activation, whereas in adults
      ACC activation follows that of temporal cortex. We suggest that these timing
      differences could be related to current maturational changes, to the ongoing
      construction of language-specific phonetic maps, and/or to more sensitive
      attentional switching as a response to speech signals in infancy.

PMID- 22155380
TI  - A preliminary report of a disposable electrical non-fiberoptic endoscope in
      thoracoscopic surgery.
AB  - PURPOSE: Conventional thoracoscopic surgery requires a camera connected to optic
      fibers and rigid rod lens to ensure the provision of adequate light and quality
      of real-time images in the operative field. However, the camera, the connected
      optic fibers and rigid rod lens are not disposable due to cost, which is a
      concern as regards potential contamination of patients. To decrease such
      contamination, we designed a disposable device of extremely low cost which we
      tested in thoracoscopic surgery in animals. DESCRIPTION: A complementary metal
      oxide-semiconductor is used for obtaining real-time image at a refresh rate of 30
      frames per second. A circumferential light was added by a light emitting diode.
      We connected wires to a universal serial bus adapter, with which the device can
      negotiate with a computer so as to control signal retrieval and adjustment of the
      light as well as focus. The device was designed to be as compact as possible. The
      contour resembled a conventional thoracoscope, but with no optic fibers and rigid
      rod lens included. EVALUATION: We used the devices to perform routine
      thoracoscopic surgical procedures, including wedge resection of the lung,
      lobectomy, esophagectomy, pericardiotomy and pleural biopsy in two 40-kg pigs
      under general anesthesia. The operating techniques were not altered while using
      this device. CONCLUSION: This disposable, electrical non-fiberoptic endoscope has
      the potential to be easily and safely used in routine thoracoscopic surgery at a
      minimal cost. Further clinical evaluation will be required to demonstrate the
      utility in human patients.

PMID- 22155381
TI  - External validation of Lintula score in Turkish acute appendicitis patients.
AB  - PURPOSE: The aim of this study was to evaluate the predictive accuracy of Lintula
      score in Turkish appendicitis patients. MATERIALS AND METHODS: Data from a total
      of 156 patients operated with the diagnosis of acute appendicitis were collected
      retrospectively. The Lintula score was constructed from nine variables (gender,
      intensity of pain, relocation of pain, pain in the right lower abdominal
      quadrant, vomiting, body temperature, guarding, bowel sounds and rebound
      tenderness) with independent diagnostic value in 156 patients. Lintula score was
      calculated for all patients. Pathological results of the resected specimen were
      determined and the diagnostic performance of the Lintula score was compared.
      RESULTS: Hoshmer-Lemeshow and ROC curve analysis was performed and area under the
      curve was 0.922. Predictive accuracy of Lintula score among Turkish appendicitis
      patients was statistically significant. CONCLUSION: Lintula score seems to be
      useful method to diagnose acute appendicitis among Turkish patients and may
      reduce the rate of negative appendectomy.

PMID- 22155382
TI  - Visualization of macroscopic cerebral vessel anatomy--a new and reliable
      technique in mice.
AB  - Visualizing rodent cerebral vasculature is an important tool in experimental
      stroke research. Intravascular perfusion with colored latex has been the method
      of choice until recently. However, latex perfusion has some technical limitations
      which compromise its reproducibility. We therefore describe a simple and
      reproducible method to visualize cerebral vessels in mice. A mixture of two
      commercially available carbon black inks is injected into the thoracic aorta
      resulting in efficient filling and high contrast visualization of cerebral
      vessels. Feasibility of this technique has been validated by identifying
      anastomotic points between anterior and middle cerebral arteries. Furthermore,
      perfusion with combined carbon inks allows visualization of significantly smaller
      vessel diameters at a higher vessel density in comparison to perfusion with
      diluted/undiluted latex. Thus, perfusion with combined carbon inks offers a
      simple, cost-effective and reproducible technique in order to visualize cerebral
      vasculature.

PMID- 22155383
TI  - A spatio-temporal filtering approach to denoising of single-trial ERP in rapid
      image triage.
AB  - Conventional search for images containing points of interest (POI) in large
      volume imagery is costly and sometimes even infeasible. The rapid image triage
      (RIT) system which is a human cognition guided computer vision technique is
      potentially a promising solution to the problem. In the RIT procedure, images are
      sequentially presented to a subject at a high speed. At the instant of observing
      a POI image, unique POI event-related potentials (ERP) characterized by P300 will
      be elicited and measured on the scalp. With accurate single-trial detection of
      such unique ERP, RIT can differentiate POI images from non-POI images. However,
      like other brain-computer interface systems relying on single-trial detection,
      RIT suffers from the low signal-to-noise ratio (SNR) of the single-trial ERP.
      This paper presents a spatio-temporal filtering approach tailored for the
      denoising of single-trial ERP for RIT. The proposed approach is essentially a non
      uniformly delayed spatial Gaussian filter that attempts to suppress the non-event
      related background electroencephalogram (EEG) and other noises without
      significantly attenuating the useful ERP signals. The efficacy of the proposed
      approach is illustrated by both simulation tests and real RIT experiments. In
      particular, the real RIT experiments on 20 subjects show a statistically
      significant and meaningful average decrease of 9.8% in RIT classification error
      rate, compared to that without the proposed approach.

PMID- 22155384
TI  - Insect-machine interface: a carbon nanotube-enhanced flexible neural probe.
AB  - We developed microfabricated flexible neural probes (FNPs) to provide a bi
      directional electrical link to the moth Manduca sexta. These FNPs can deliver
      electrical stimuli to, and capture neural activity from, the insect's central
      nervous system. They are comprised of two layers of polyimide with gold
      sandwiched in between in a split-ring geometry that incorporates the bi
      cylindrical anatomical structure of the insect's ventral nerve cord. The FNPs
      provide consistent left and right abdominal stimulation both across animals and
      within an individual animal. The features of the stimulation (direction,
      threshold charge) are aligned with anatomical features of the moth. We also have
      used these FNPs to record neuronal activity in the ventral nerve cord of the
      moth. Finally, by integrating carbon nanotube (CNT)-Au nanocomposites into the
      FNPs we have reduced the interfacial impedance between the probe and the neural
      tissue, thus reducing the magnitude of stimulation voltage. This in turn allows
      use of the FNPs with a wireless stimulator, enabling stimulation and flight
      biasing of freely flying moths. Together, these FNPs present a potent new
      platform for manipulating and measuring the neural circuitry of insects, and for
      other nerves in humans and other animals with similar dimensions as the ventral
      nerve cord of the moth.

PMID- 22155385
TI  - Metabotropic glutamate receptor 1 (mGluR1): antibody specificity and receptor
      expression in cultured primary neurons.
AB  - The availability of high quality, well-characterized antibodies for molecular and
      cellular neuroscience studies is important. However, not all available antibodies
      are rigorously evaluated, nor are limitations of particular antibodies often
      reported. We have examined a panel of currently available mGluR1 antibodies and
      have identified which ones are selective for use by western blots and
      immunocytochemistry. We have also specifically determined whether the antibodies
      cross-react to recognize mGluR5, by examining (1) tissue from both mGluR1 and
      mGluR5 knock-out mice and (2) primary cortical cultures, in which mGluR5 is
      widely expressed but mGluR1 is not. Together, these data provide a baseline
      characterization of antibodies that can and cannot be reliably used in these
      types of studies, and will hopefully facilitate and positively impact the
      research efforts of others studying mGluR1.

PMID- 22155386
TI  - A non-human primate model of bipedal locomotion under restrained condition
      allowing gait studies and single unit brain recordings.
AB  - For decades, several animal models of locomotion have allowed a better
      understanding of the basic physiological mechanisms of gait. However, unlike most
      of the mammals, the Order Primates is characterized by fundamental changes in
      locomotor behaviour. In particular, some primates use a specific pattern of
      locomotion and are able to naturally walk bipedally due possibly to a specific
      supra-spinal control of locomotion. These features must be taken into account
      when one considers to study the intrinsic properties of human gait. Thus, an
      experimental model of bipedal locomotion allowing precise and reproducible
      analysis of gait in non-human primate is still lacking. This study describes a
      non-human primate model of bipedal locomotion under restrained condition. We
      undertook a kinematic and biomechanic study in three Macaca fascicularis trained
      to walk bipedally on a treadmill. One of the primate was evaluated in complete
      head fixation. Gait visual analysis and electromyographic recordings provided
      pertinent description of the gait pattern. Step frequencies, step lengths, cycle
      and stance phase durations were correlated with Froude number (dimensionless
      velocity), whereas swing phase durations remained non-correlated. Gait patterns
      observed in our model were similar to those obtained in freely bipedal Macaca
      fuscata and to a lesser extend to Humans. Gait pattern was not modified by head
      fixation thereby allowing us to perform precise and repetitive micro electrode
      recordings of deep cerebral structures. Thus, the present model could provide a
      pertinent pre-clinical tool to study gait parameters and their neuronal control
      but also could be helpful to validate new therapeutics interventions.

PMID- 22155387
TI  - Green leaf divinyl ether synthase: gene detection, molecular cloning and
      identification of a unique CYP74B subfamily member.
AB  - Enzymes of the CYP74 family (P450 superfamily) play a key role in the plant
      lipoxygenase signalling cascade. Recently we detected a pathogen inducible
      divinyl ether synthase (DES) in flax leaves [Chechetkin, Blufard, Hamberg,
      Grechkin, 2008]. This prompted us to examine the CYP74 genes in the flax leaf
      transcriptome. Since the flax genome is not sequenced, we used the PCR approach
      with degenerate primers related to the conserved domains of selected CYP74 genes;
      this revealed several CYP74 transcripts in flax leaves. One transcript belongs to
      the previously described allene oxide synthase (LuAOS, CYP74A, GenBank ID:
      U00428.1). Another one contains the ORF (1473 bp) of an unknown CYP74B16 gene.
      Three more nearly identical sequences, including one expressed pseudogene, were
      also identified. The recombinant CYP74B16 protein expressed in Escherichia coli
      had 491 amino acid residues and MW of 56 kDa. The preferred substrate of this
      enzyme is the 13-hydroperoxide of alpha-linolenic acid, and the reaction product
      was identified by mass spectrometry, NMR and UV spectroscopy as the divinyl ether
      (9Z,11E)-12-[(1'Z,3'Z)-hexadienyloxy]-9,11-dodecadienoic acid, (omega5Z)
      etherolenic acid. All previously known CYP74B subfamily enzymes are hydroperoxide
      lyases. The novel flax enzyme CYP74B16 (LuDES) is an unprecedented DES member of
      the CYP74B subfamily.

PMID- 22155388
TI  - Extract of Salvia miltiorrhiza (Danshen) induces Nrf2-mediated heme oxygenase-1
      expression as a cytoprotective action in RAW 264.7 macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Danshen (Salvia miltiorrhiza) is widely used in
      traditional herbal medicines for relief of a variety of symptoms related to
      complications arising from vascular diseases such as hypertension, diabetes, and
      atherosclerosis. Induction of heme oxygenase-1 (HO-1) expression protects against
      oxidative stress-induced cell damage, which plays an important role in
      cytoprotection in a variety of pathological models. MATERIALS AND METHODS: In the
      present study, we investigated the effect of Danshen on the up-regulation of HO
      1, an inducible and cytoprotective enzyme in RAW 264.7 macrophages. Molecular
      mechanisms underlying the effects, especially protective effects, was elucidated
      by analyzing the activation of transcription factors and their upstream
      signalling, and by evaluating the inhibitory effect of HO-1 on ROS production.
      RESULTS: Danshen induced HO-1 mRNA expression and protein production, and nuclear
      translocation of NF-E2-related factor 2 in RAW 264.7 macrophages. Pharmacological
      inhibitors of PI3K/Akt and MEK1 attenuated HO-1 induction in Danshen-stimulated
      RAW 264.7 macrophages. Furthermore, Danshen pretreatment reduced intracellular
      production of reactive oxygen species after stimulation with hydrogen peroxide;
      this effect was reversed by the HO-1 inhibitor ZnPP. CONCLUSION: Danshen induced
      HO-1 expression through PI3K/Akt-MEK1-Nrf2 pathway and reduced intracellular
      production of reactive oxygen species via induction of HO-1 expression. The
      results support a role of HO-1 in the cytoprotective effect of Danshen.

PMID- 22155389
TI  - Evaluation of the immunomodulatory properties in mice and in vitro anti
      inflammatory activity of cycloartane type saponins from Astragalus species.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus roots are used to treat leukemia and
      for their wound healing properties in Southeast Anatolia-Turkey. MATERIALS AND
      METHODS: In vivo studies to investigate the effects of two Astragalus saponins
      were carried out on the immune response cytokines by using six to eight weeks old
      male Swiss albino mice. The production of IL-1beta, TGF-1beta, TNF-alpha, IL-2,
      IL-4 and IFN-gamma cytokines was determined by ELISA. The spleen and lymph nodes,
      isolated from the mice subjects, were analyzed to realize induction of the
      surface antigen productions for IL-2Ralpha (CD25) and CD69. In addition, their
      effects on the targets of inflammation such as NF kappaB, iNOS and NAG-1 were
      investigated in cell-based assays. RESULTS: The results suggested that AST VII
      and Mac B had positive effect on Th1 cytokine release (IL-2 and IFN-gamma), and
      suppression on Th2 cytokine production (IL-4). The immunohistochemical results
      exhibited induction of both IL-Ralpha (CD25) and CD69 surface receptors
      justifying the Th1 cytokine release. The compounds did not affect NF-kappaB or
      NAG-1 activity but iNOS activity was inhibited by Mac B with an IC(50) of 156
      MUg/ml. CONCLUSIONS: The results show that Ast VII and Mac B create powerful
      immunoregulatory effects without the stimulation of inflammatory cytokines in
      mice, and have no significant effect on the inflammatory cellular targets in
      vitro.

PMID- 22155390
TI  - Antiosteoporotic activity of Davallia formosana.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] In Taiwanese folk medicine, Davallia
      formosana is used to treat bone diseases, including osteoporosis. AIM: This study
      evaluated the anti-osteoporotic effect of ethanolic extract derived from Davallia
      formosana (DFE). MATERIALS AND METHODS: In this in vitro study, we investigated
      the inhibitory action of DFE on RANKL-stimulated osteoclastogenesis. The in vivo
      effects of DFE on bone metabolism were evaluated using ovariectomized (OVX) rats
      orally administered DFE (200, 500 mg/kg), alendronate (2.5 mg/kg, three times a
      week) or its vehicle for 12 weeks. RESULTS: This in vitro study demonstrated that
      DFE inhibited osteoclast differentiation, and also isolated the active component,
      (-)-epicatechin 3-O-beta-D-allopyranoside (ECAP). DFE did not affect the body or
      vaginal weight in OVX rats. The bone mineral density and bone calcium content in
      OVX rats were lower in the control group showing that DFE was able to prevent
      significant bone loss. In addition, the three point bending test and the
      microcomputer tomography scanning showed that DFE treatment enhanced bone
      strength and inhibited the deterioration of trabecular microarchitecture. In the
      biochemical assay, DFE decreased urinary deoxypyridinoline and calcium
      concentrations, but did not inhibit serum alkaline phosphatase activities,
      indicating that it ameliorated bone loss via inhibition of bone reabsorption.
      CONCLUSIONS: These results suggest that DFE may represent a useful remedy for the
      treatment of bone reabsorption diseases such as osteoporosis. In addition, ECAP
      could be used as a marker compound to control the quality of DFE.

PMID- 22155391
TI  - Anxiolytic-like effects of acute and chronic treatment with Achillea millefolium
      L. extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Achillea millefolium L. (Asteraceae), known as
      yarrow ("mil folhas"), has been used as folk medicine for gastrointestinal
      disorders, inflammation, anxiety, and insomnia. AIM: To evaluate the potential
      anxiolytic-like effect of hydroalcoholic extract of Achillea millefolium L. in
      animal models. METHODS: The present study evaluated the effects of the
      hydroalcoholic extract from the aerial parts of Achillea millefolium L. in mice
      subjected to the elevated plus-maze, marble-burying, and open-field tests.
      Additionally, the GABA(A)/benzodiazepine (BDZ) mediation of the effects of
      Achillea millefolium was evaluated by pretreatment with the noncompetitive
      GABA(A) receptor antagonist picrotoxin and the BDZ antagonist flumazenil and by
      [(3)H]-flunitrazepam binding to the BDZ site on the GABA(A) receptor. RESULTS:
      Achillea millefolium exerted anxiolytic-like effects in the elevated plus-maze
      and marble-burying test after acute and chronic (25 days) administration at doses
      that did not alter locomotor activity. This behavioral profile was similar to
      diazepam. The effects of Achillea millefolium in the elevated plus-maze were not
      altered by picrotoxin pretreatment but were partially blocked by flumazenil.
      Furthermore, Achillea millefolium did not induce any changes in [(3)H]
      flunitrazepam binding. CONCLUSION: The results indicate that the orally
      administered hydroalcoholic extract of Achillea millefolium L. exerted anxiolytic
      like effects that likely were not mediated by GABA(A)/BDZ neurotransmission and
      did not present tolerance after short-term, repeated administration.

PMID- 22155392
TI  - Hematopoietic and myeloprotective activities of an acidic Angelica sinensis
      polysaccharide on human CD34+ stem cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (AS) is a Chinese herbal
      medicine traditionally used in prescriptions for replenishing blood and treating
      abnormal menstruation and other women's diseases. AIM OF THE STUDY: This study
      aimed to separate and identify the major hematopoietic fraction from Angelica
      sinensis polysaccharides (ASPS), and to investigate the myeloprotective activity
      of the major bioactive fraction of ASPS as a possible supporting agent for cancer
      treatments. MATERIALS AND METHODS: The ASPS was fractionated with DEAE-Sepharose
      CL-6B column to obtain four fractions (F1, F2, F3 and F4). Each fraction was
      cultured with human peripheral blood mononuclear cells (MNCs) to collect
      conditioned medium (CM). The hematopoietic ability of various MNC-CM was then
      evaluated by the colony-forming assay on CD34(+) cells collected by the MACS
      method from human umbilical cord blood (UCB). In myeloprotective experiment,
      Adriblastina was used to act as the myelosuppressive agent. The monosaccharide
      composition of ASPS was analyzed by high-performance anion-exchange
      chromatography-pulse amperometric detector. RESULTS: The F2 fraction, which was
      found to have the highest hematopoietic activity, stimulated the human peripheral
      blood MNCs to secret GM-CSF and IL-3. F2 could also protect the hematopoietic
      function of CD34(+) cells from Adriblastina. F2 occupies 19% of ASPS and contains
      0.53% protein. The monosaccharide composition of F2 was arabinose (51.82%),
      fructose (1.65%), galactose (29.96%), glucose (4.78%) and galacturonic acid
      (14.80%), with molecular weight 2.5-295 kDa. CONCLUSIONS: The bioactive fraction
      identified and fractionated from ASPS may be used as a health-promoting agent for
      anemia patients and cancer patients under chemoradiation treatment.

PMID- 22155393
TI  - Appraisal on the wound healing and anti-inflammatory activities of the essential
      oils obtained from the cones and needles of Pinus species by in vivo and in vitro
      experimental models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: According to ethnobotanical data, Pinus species
      have been used against rheumatic pain and for wound healing in Turkish folk
      medicine. Essential oils from the cones and needles of five different Pinus
      species (Pinus brutia Ten., Pinus halepensis Mill., Pinus nigra Arn., Pinus pinea
      L. and Pinus sylvestris L.) were evaluated for their in vivo wound healing and
      anti-inflammatory activities. MATERIALS AND METHODS: In vivo wound healing
      activity of the ointments prepared from essential oils was evaluated by linear
      incision and circular excision experimental wound models subsequently
      histopathological analysis and hydroxyproline content. Furthermore, the essential
      oils were screened for anti-hyaluronidase activity. Additionally anti
      inflammatory activity was assessed by using the method of Whittle, which is based
      on the inhibition of acetic acid-induced increase in capillary permeability.
      RESULTS: The essential oils obtained from the cones of Pinus pinea and Pinus
      halepensis demonstrated the highest effects on the wound healing activity models.
      On the other hand, the rest of the essential oils did not show any significant
      wound healing and anti-inflammatory activities. CONCLUSION: The experimental
      study revealed that essential oils obtained from the cones of Pinus pinea and
      Pinus halepensis display remarkable wound healing activity.

PMID- 22155394
TI  - Modulation of LPS-stimulated neuroinflammation in BV-2 microglia by Gastrodia
      elata: 4-hydroxybenzyl alcohol is the bioactive candidate.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (Orchidaceae, GE) a
      traditional plant in Oriental countries is known for its enormous benefits to
      treat headaches, dizziness, vertigo and convulsive illnesses. In the present
      study, the ethnopharmacological role of GE in neuroinflammation mediated by
      activated microglia and the mechanisms underlying were reported. MATERIALS AND
      METHODS: BV-2 microglia activated by lipopolysaccharide (LPS) was employed and
      the effects of GE on corresponding neuroinflammatory parameters were assessed.
      RESULTS: GE extract inhibited LPS-stimulated production of inflammatory cytokines
      and down regulated the c-Jun NH(2)-Terminal Kinase (JNK) and nuclear factor-kappa
      B (NF-kappaB) signaling pathways, which are known to be involved in
      neuroinflammation. Further, inhibition of NO and iNOS by 4-hydroxybenzyl alcohol
      (4-HBA), one of the active constituent of GE in LPS-stimulated BV-2 cells suggest
      that 4-HBA might be the bioactive candidate. CONCLUSION: GE extract and its
      active constituent 4-HBA could be further exploited to mitigate microglial
      activation and may be developed as a new therapeutic remedy in treating various
      neuroinflammatory diseases.

PMID- 22155395
TI  - The ability of an ethanol extract of Cinnamomum cassia to inhibit Src and spleen
      tyrosine kinase activity contributes to its anti-inflammatory action.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Blume (Aceraceae) has been
      traditionally used to treat various inflammatory diseases such as gastritis.
      However, the anti-inflammatory mechanism of Cinnamomum cassia has not been fully
      elucidated. This study examined the anti-inflammatory mechanism of 95% ethanol
      extract (Cc-EE) of Cinnamomum cassia. MATERIALS AND METHODS: The effect of Cc-EE
      on the production of inflammatory mediators in RAW264.7 cells and peritoneal
      macrophages was investigated. Molecular mechanisms underlying the effects,
      especially inhibitory effects, was elucidated by analyzing the activation of
      transcription factors and their upstream signaling, and by evaluating the kinase
      activity of target enzymes. RESULTS: Cc-EE of Cinnamomum cassia diminished the
      production of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and
      prostaglandin (PG)E(2), in lipopolysaccharide (LPS)-activated RAW264.7 cells and
      peritoneal macrophages in a dose-dependent manner. Cc-EE also blocked mRNA
      expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-alpha
      by suppressing the activation of nuclear factor (NF)-kappaB, and simultaneously
      inhibited its upstream inflammatory signaling cascades, including spleen tyrosine
      kinase (Syk) and Src. Consistent with these findings, the extract directly
      blocked the kinase activities of Src and Syk. CONCLUSION: Cc-EE exerts strong
      anti-inflammatory activity by suppressing Src/Syk-mediated NF-kappaB activation,
      which contributes to its major ethno-pharmacological role as an anti-gastritis
      remedy. Future work will be focused on determining whether the extract can be
      further developed as an anti-inflammatory drug.

PMID- 22155396
TI  - Mutagenicity, antimutagenicity and cytotoxicity evaluation of South African
      Podocarpus species.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Four species of Podocarpus are used in
      traditional medicine both in human and animal healthcare in South Africa. In
      vitro pharmacological screening of leaf and stem extracts of these species
      exhibited potent antimicrobial, anti-inflammatory, anti-tyrosinase, anthelmintic,
      acetylcholinesterase inhibitory and antioxidant activities. AIM OF THE STUDY: To
      investigate the mutagenicity, antimutagenicity and cytotoxicity effects of leaf
      and stem extract of South African Podocarpus species. MATERIAL AND METHODS: The
      mutagenicity and cytotoxic effects of extracts from four species of Podocarpus
      were tested using the Salmonella/microsome assay with and without metabolic
      activation, based on the plate-incorporation method and neutral red uptake (NRU)
      assay respectively. Five Salmonella typhimurium tester strains; TA98, TA100,
      TA102, TA1535 and TA1537 were used for mutagenicity testing. The relative
      cytotoxicity of the extracts was assessed by determining their NI(50) values (50%
      inhibition of NRU). RESULTS: The extracts did not show any mutagenic effects
      against all the tester strains with or without metabolic activation. All extracts
      demonstrated a strong antimutagenic effect on the mutations induced by 4NQO,
      decreasing its mutagenic effect in a dose-dependent manner. Strong cytotoxic
      effects were exhibited by petroleum ether extracts as compared to 80% ethanol
      extracts. When HepG2 cells were in contact with plant extracts in an increasing
      concentration, slopes of NRU decreased (highest-lowest %) following a
      concentration-dependent pattern. For 80% ethanol extracts, the most toxic extract
      in terms of percentage viability was leaves of Podocarpus falcatus whereby at 0.2
      mg/ml, the viability of the cells was 38.9%. Stem extract of Podocarpus
      latifolius was the most toxic among PE extracts, giving a percentage viability of
      46.4 at 0.1 mg/ml. CONCLUSION: Absence of mutagenicity does not indicate lack of
      toxicity, as was observed from these extracts. These findings will help in
      assessing the safety measures to be considered in the use of these species and
      also the need to determine the cytotoxic potential of these species against
      various forms of human cancer cells.

PMID- 22155397
TI  - Isolation of active constituents from cherry laurel (Laurocerasus officinalis
      Roem.) leaves through bioassay-guided procedures.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The fresh leaves of Laurocerasus officinalis
      Roem. (Rosaceae) are externally used against pain and feverish symptoms in
      Turkish folk medicine. AIM OF THE STUDY: Effects of the extracts, fractions and
      isolated compounds from the leaves of L. officinalis were investigated using in
      vivo models of inflammation and pain in mice. METHODS: The crude ethanolic
      extract from the leaves of plant was sequentially fractionated into five
      subextracts; explicitly, n-hexane, chloroform, ethyl acetate (EtOAc), n-butanol,
      and remaining water extracts. Further studies were carried out on the most active
      EtOAc subextract was further subjected to fractionation through column
      chromatography. For the anti-inflammatory activity, carrageenan-induced hind paw
      edema and acetic acid-induced increase in capillary permeability models, and for
      the antinociceptive activity p-benzoquinone-induced writhing test in mice were
      employed. RESULTS: Ethanolic extract of the leaves was shown to possess
      significant inhibitory activity in the assay methods without inducing any gastric
      damage. Through bioassay-guided fractionation and isolation procedures three
      phenolic compounds, 2-O-beta-D-glucopyranosyl-2-hydroxyphenyl-acetic acid (1),
      kaempferol-3-O-beta-D-xylopyranosyl-(1->2)-O-beta-D-glucopyranoside (2) and (+)
      catechin (3) were isolated from the active fraction and their structures were
      elucidated by spectral techniques (1D and 2D NMR, ESIMS). CONCLUSION: The
      experimental data verified that Laurocerasus officinalis leaves displayed
      remarkable anti-inflammatory and antinociceptive activity.

PMID- 22155398
TI  - Advantages of the lognormal approach to determining reference change values for N
      terminal propeptide B-type natriuretic peptide.
AB  - BACKGROUND: Serial measurement of NT-proBNP is performed routinely in the
      monitoring and assessment of the effectiveness of therapy in patients being
      treated for chronic heart failure (CHF). Intra-individual changes in NT-proBNP
      levels over time are compared typically to a reference change value (RCV)
      determined using either a standard [i.e., nested analysis of variance (nANOVA)]
      or a lognormal approach. The RCV defines the minimum percent change in serial
      analyte values that exceeds the percent change expected due to biological
      variation alone. Currently, there is no consensus on which approach (nANOVA or
      lognormal) to determining RCV is better. AIMS: Based on these considerations, we
      aimed to illustrate the impact of data transformation on the calculation of the
      biological variation of NT-proBNP and discuss the utility of logarithmic
      transformation in monitoring patients with heart failure. METHODS: 15 healthy
      subjects were enrolled after informed consent; 5 blood specimens were collected
      twice a week. Nested ANOVA from replicate analyses was applied to obtain
      components of biological variation, on the raw data and after data
      transformation. RESULTS: NT-proBNP distribution being highly skewed required data
      transformation. Natural log transformation yielded normalization. An example
      demonstrates that for untransformed values the RCV was overestimated for low
      concentrations of NT-proBNP and underestimated for higher concentrations.
      CONCLUSIONS: Log-transformed data are often used in the establishment of
      reference intervals for evaluating laboratory tests results in clinical practice,
      especially when the reference interval data are not Gaussian distributed. As log
      normal approach is the best approach to determining RCV values we encourage its
      use assessing the clinical utility of NT-proBNP serial testing. We propose that
      the log-normal approach becomes the standard approach to determining RCV and
      replaces the use of nANOVA.

PMID- 22155399
TI  - Characterization of [3H]Lu AE60157 ([3H]8-(4-methylpiperazin-1-yl)-3
      phenylsulfonylquinoline) binding to 5-hydroxytryptamine6 (5-HT6) receptors in
      vivo.
AB  - The serotonin6 (5-HT(6)) receptor has received attention for its proposed role in
      cognitive impairments associated with schizophrenia and Alzheimer's disease. This
      has lead to a search for selective 5-HT(6) receptor ligands useful for in vivo
      imaging in animals and humans. The novel 5-HT(6) receptor antagonist Lu AE60157
      (8-(4-methylpiperazin-1-yl)-3-phenylsulfonylquinoline) displays high affinity for
      the human (h) 5-HT(6) receptor (K(d) 0.2nM), and broad profiling in 60 additional
      binding and enzyme assays showed that Lu AE60157 displays 16-fold selectivity to
      the h5-HT(2A) receptor (K(i) 3.2nM) and >100-fold selectivity to all other
      evaluated targets. Lu AE60157 was labeled with tritium in the N-methyl group and
      evaluated as a radioligand in vitro as well as in vivo in rats and mice.
      Autoradiography experiments showed that [(3)H]Lu AE60157 bound preferentially to
      rat brain regions with expected high 5-HT(6) receptor density. Furthermore,
      [(3)H]Lu AE60157 showed good brain penetration after systemic administration and
      high (about 75%) specific in vivo binding to the striatal 5-HT(6) receptor in
      rats. The striatal binding of [(3)H]Lu AE60157 was fully displaced by selective 5
      HT(6) receptor antagonists (SB-742457; Lu AE58054) and antipsychotics known to
      inhibit the binding of 5-HT(6) receptors in vitro (clozapine; olanzapine;
      sertindole), but was not displaced by antipsychotics lacking high 5-HT(6)
      receptor affinities (risperidone; haloperidol; quetiapine). No specific binding
      to mouse brain tissue in vivo could be obtained. In conclusion, [(3)H]Lu AE60157
      is suitable for measuring in vivo occupancies of 5-HT(6) receptor ligands in rat
      brain regions in which 5-HT(2A) receptors do not interfere.

PMID- 22155400
TI  - Antivirus and immune enhancement activities of sulfated polysaccharide from
      Angelica sinensis.
AB  - This study is to synthesize sulfated Angelica polysaccharides (APSs) and
      investigate the activity of one of the sulfated derivatives APS-1 on murine
      leukemia virus in vivo. Six sulfated derivatives with degree of sulfation ranging
      from 0.68 to 1.91 were obtained. And the virus replication was inhibited by APS-1
      at the dose of 10 and 30 mg/kg (26% and 30% inhibition respectively).
      Furthermore, both the percentage of CD4(+) cells and CD4(+)/CD8(+) ratio in
      peripheral blood cells were significantly enhanced by APS-1 at 3-30 mg/kg. In
      addition, the reduced thymus/body weight index by murine leukemia virus infection
      was increased by ASP-1 in a dose dependent manner. These results suggest that APS
      1 could not only inhibit virus replication, but also improve the immune function.
      APS-1 may be a potential new and better antiviral drug.

PMID- 22155401
TI  - Concentration selective hydration and phase states of hydroxyethyl cellulose
      (HEC) in aqueous solutions.
AB  - Solution behaviour of hydroxyethyl cellulose (HEC) is reported in the polymer
      concentration range spanning over two decades (c=0.002-5% (w/v)). The results
      conclude the following: (i) dilute solution regime prevailed for c<0.2% (w/v),
      flexible HEC fibres of typical length ~ 1 MUm and persistence length ~ 10 nm were
      found here, (ii) for 0.2<c<1% (w/v), a semidilute phase comprising soluble
      aggregates of hydrated HEC fibrils were observed with the material exhibiting
      viscoelastic behaviour and (iii) when 1<c<5% (w/v) the solution behaved with melt
      like attributes with substantial embedded heterogeneity; viscous to elastic
      transition was observed in this region. Raman spectral, and DSC data indicated
      distinctive hydration of HEC fibres in the aforesaid concentration regimes. Cole
      Cole plots revealed phase homogeneity and miscibility was limited to
      concentrations less than ~2% (w/v). For higher polymer concentrations, strong
      fibre-fibre interactions prevailed and samples became heterogeneous.

PMID- 22155402
TI  - Laccase-mediated system pretreatment to enhance the effect of hydrogen peroxide
      bleaching of cotton fabric.
AB  - This study evaluates the bleaching efficiency of the hydrogen peroxide bleaching
      process combined with laccase-mediated system pretreatment (LMS-HPBP) in the
      treatment of scoured cotton fabric. By changing the factors of laccase-mediated
      system pretreatment and the hydrogen peroxide bleaching process and examining the
      subsequent whiteness value and retained tensile strength of the samples, we find
      three LMS-HPBP processes that are more environment friendly than the conventional
      hydrogen peroxide bleaching process (CHPBP): (i) bleaching with lower dosage of
      hydrogen peroxide; (ii) bleaching at reduced temperature; (iii) bleaching for
      shortened duration. Whiteness, retained tensile strength and K/S values of cotton
      fabric samples treated by i-iii processes were similar to or higher than those by
      CHPBP. X-ray diffraction (XRD) analysis also demonstrated that the three
      processes rendered fabric of both lower crystallinity and bigger crystallite size
      than those by CHPBP. In addition, the "green" short-flow process was developed to
      treat cotton fabric and the results obtained shows this method is feasible as a
      new energy-saving process.

PMID- 22155403
TI  - Adsorption of Hg2+, Cu2+ and Zn2+ ions from aqueous solution using formaldehyde
      cross-linked modified chitosan-thioglyceraldehyde Schiff's base.
AB  - A chitosan-thioglyceraldehyde Schiff's base cross-linked magnetic resin (CSTG)
      was prepared and characterized using various instrumental methods. Then, the
      prepared resin was used for comparative studies on the removal of toxic metal
      ions like: Hg(2+), Cu(2+) and Zn(2+) from aqueous solutions. The effects of the
      initial pH value of the solution, contact time, the initial metal ion
      concentration and temperature on the adsorption capacity of the composite were
      investigated. The kinetics data were analyzed by pseudo-first order and pseudo
      second order equations. The adsorption kinetics was well described by the pseudo
      second order equation, and the adsorption isotherms were better fitted by the
      Langmuir equation. The maximum theoretical adsorption capacities of the CSTG
      resin for Hg(2+), Cu(2+) and Zn(2+) were found to be 98+/-2, 76+/-1 and 52+/-1 mg
      g(-1), respectively. The negative values of Gibbs free energy of adsorption
      (DeltaG(ads degrees ) indicated the spontaneity of the adsorption of all metal
      ions on the novel resin.

PMID- 22155405
TI  - Genetic variations of prostate stem cell antigen (PSCA) contribute to the risk of
      gastric cancer for Eastern Asians: a meta-analysis based on 16792 individuals.
AB  - The associations between polymorphisms of prostate stem cell antigen (PSCA
      rs2294008C>T and -rs2976392G>A) and gastric cancer (GC) risk for Eastern Asians
      have been commonly studied, but the results were conflicting. The aim of the
      present study was to further assess the associations by the method of meta
      analysis. The databases of Medline, Embase and CNKI (up to May 25th, 2011) were
      retrieved to identify eligible case-control studies. Odds ratio (OR) and 95%
      confidence interval (95%CI) were used to present the strength of the
      associations. In total, eight case-control studies in seven articles with 16792
      individuals (9738 cases of GC and 7054 controls) were included in this meta
      analysis. Through quantitative analyses, we found that T allele of rs2294008C>T
      and A allele of rs2976392G>A were significantly associated with increased GC risk
      [rs2294008C>T: OR (95%CI)=1.31 (1.22-1.42), P(z-test)<0.001,
      P(heterogeneity)=0.166 for TT vs. C carriers; rs2976392G>A: OR (95%CI)=1.36(1.24
      1.50), P(z-test)=0.015, P(heterogeneity)=0.111 for AA vs. G carriers]. The
      results of subgroup analyses (according to histopathology, countries and sources
      of controls) indicated that T allele of rs2294008C>T and A allele rs2976392G>A
      were associated with increased risk of both intestinal- and diffuse-type GC, and
      associated with increased risk of GC for Chinese, Japanese, Koreans, PCC and
      HCC/PHCC. Furthermore, T allele of rs2294008C>T was also associated with
      increased risk of cardia and non-cardia GC, and associated with increased risk of
      GC for males and females. Besides those, this meta-analysis also indicated that
      the interactions between T allele of rs2294008C>T and A allele of rs2976392G>A
      was associated with increased risk of GC (A-T vs. G-T: OR=1.16, 95%CI=1.06-1.27,
      P(z-test)=0.001, P(heterogeneity)=0.835). Although modest limitations and
      potential bias cannot be eliminated, this meta-analysis suggests that PSCA 
      rs2294008C>T and -rs2976392G>A are potential factors of GC development for
      Eastern Asians, and future work may incorporate these findings and evaluate these
      variants as potential markers for screening and early diagnosis of GC.

PMID- 22155404
TI  - Depletion of endogenous noradrenaline does not prevent spinal cord plasticity
      following peripheral nerve injury.
AB  - The present study examined the role of endogenous noradrenaline on glial and
      neuronal plasticity in the spinal cord in rats after peripheral nerve injury. An
      intrathecal injection of dopamine-beta-hydroxylase antibody conjugated to saporin
      (DbetaH-saporin) completely depleted noradrenergic axons in the spinal cord and
      also reduced noradrenergic neurons in the locus coeruleus (A6) and A5
      noradrenergic nucleus in the brainstem and noradrenergic axons in the
      paraventricular nucleus of the hypothalamus. DbetaH-saporin treatment itself did
      not alter mechanical withdrawal threshold, but enhanced mechanical
      hypersensitivity and intrathecal clonidine analgesia after L5-L6 spinal nerve
      ligation. In the spinal dorsal horn of spinal nerve ligation rats, DbetaH-saporin
      treatment increased choline acetyltransferase immunoreactivity as well as
      immunoreactivity in microglia of ionized calcium binding adaptor molecule 1[IBA1]
      and in astrocytes of glial fibrillary acidic protein, and brain-derived nerve
      growth factor content. DbetaH-saporin treatment did not, however, alter the
      fractional release of acetylcholine from terminals by dexmedetomidine after nerve
      injury. These results suggest that endogenous tone of noradrenergic fibers is not
      necessary for the plasticity of alpha2-adrenoceptor analgesia and glial
      activation after nerve injury, but might play an inhibitory role on glial
      activation. PERSPECTIVE: This study demonstrates that endogenous noradrenaline
      modulates plasticity of glia and cholinergic neurons in the spinal cord after
      peripheral nerve injury and hence influences the pathophysiology of spinal cord
      changes associated with neuropathic pain.

PMID- 22155406
TI  - Distribution of ventilation in pregnant Shetland ponies measured by Electrical
      Impedance Tomography.
AB  - The regional distribution of ventilation in conscious standing pregnant Shetland
      pony mares was investigated by Electrical Impedance Tomography (EIT). Six ponies
      were repeatedly examined a minimum of four weeks prior to (antepartum, AP) until
      three weeks after parturition (postpartum, PP). From the cross-sectional
      ventilation image the ventral to dorsal (V/D), left to right (L/R) ventilation
      distribution ratio and the relative ventilation in four horizontal regions of
      interest (ROI) placed symmetrically in the chest was analyzed. Antepartum V/D was
      0.74 +/- 0.09 on day -28 +/- 3 (AP28) and decreased to 0.68 +/- 0.10 on day -3 +/
      2 (AP3). Postpartum V/D increased significantly (p<0.05) to 0.96 +/- 0.08 on day
      7 +/- 2 (PP7). The L/R ventilation distribution remains unaffected. Ventilation
      in the most ventral ROI was significantly lower on days AP28 and AP3 compared to
      PP7. These results suggest that in Shetland ponies late pregnancy compromises the
      ventilation in ventral (dependent) lung regions. We demonstrated the feasibility
      of a repeated EIT measurement in standing conscious ponies.

PMID- 22155407
TI  - Functional roles of Notch signaling in the cnidarian Nematostella vectensis.
AB  - Notch signaling is among the oldest of known Metazoan signaling pathways and is
      used in a multitude of developmental contexts to effect cellular differentiation,
      specification and the maintenance of stem cell state. Here we report the
      isolation and expression of the canonical Notch signaling pathway in the early
      branching metazoan Nematostella vectensis (Anthozoa, Cnidaria) during embryonic
      and larval development. We have used pharmacological treatment, morpholino
      knockdown, and dominant negative misexpression experiments to demonstrate that
      Notch signaling acts to mediate cnidogenesis, the development of cnidarian
      specific neural effecter cells. Notch signaling often results in the
      transcriptional activation of NvHes genes, a conserved family of bHLH
      transcription factors. A loss of Notch signaling through use of pharmacological
      inhibition or knock-down of the Notch effecter gene Suppressor of Hairless Su(H)
      similarly results in a loss of cnidocyte cell fate. We also provide evidence that
      Notch signaling is responsible for certain aspects of neurogenesis in developing
      N. vectensis planula in which disruption of Notch cleavage via the
      pharmacological agent DAPT results in increased expression of neural marker genes
      in vivo. This data suggests that Notch signaling acting on components of the
      developing nervous system is an ancient role of this pathway. The shared
      requirement of Notch signaling for the development of both cnidocytes and neurons
      further supports the hypothesis that cnidocytes and neurons share common origins
      as multifunctional sensory-effecter cells.

PMID- 22155408
TI  - Androgen regulated HN1 leads proteosomal degradation of androgen receptor (AR)
      and negatively influences AR mediated transactivation in prostate cells.
AB  - We recently reported that hematological and neurological expressed 1 (HN1) is a
      ubiquitously expressed, EGF-regulated gene. Expression of HN1 in prostate cell
      lines down-regulates PI3K-dependent Akt activation. Here, we investigate whether
      HN1 is regulated by androgens through the putative androgen response elements
      (AREs) found in its promoter. Knockdown of HN1 expression by siRNA silencing
      leads to an increase in Akt((S473)) phosphorylation, resulting in the
      translocation of androgen receptor (AR) to the nucleus; these effects can be
      abrogated by the non-specific Akt inhibitor LY294002 but not by the ERK inhibitor
      PD98059. Furthermore, HN1 overexpression correlates with an increase in
      ubiquitination-mediated degradation (a consequence of the decrease in S213/210
      phosphorylation of AR), ultimately resulting in the down-regulation of AR
      mediated expression of the KLK3, KLK4, NKX3.1 and STAMP2 genes. We also found
      that HN1 overexpression suppresses colony formation as well as R1881-mediated
      growth in LNCaP cells, while it has the opposite effect (increasing colony
      formation but not proliferation) in PC-3 and DU145 cells. Therefore, we suggest
      that HN1 maintains a balance between the androgen-regulated nuclear translocation
      of AR and steady-state Akt phosphorylation, predominantly in the absence of
      androgens. If so, the balance between cell growth and EGF- and AR-signaling must
      be tightly regulated by HN1. This work has important implications for prostate
      cancer research, as AR, EGFR and HN1 are known to be highly expressed in prostate
      adenocarcinomas.

PMID- 22155409
TI  - Effect of gamma-cyclodextrin on the in vitro skin permeation of a steroidal drug
      from nanoemulsions: impact of experimental setup.
AB  - Numerous reports on the enhancement effect of cyclodextrins (CDs) on the skin
      permeation of dermally applied drugs exist, the majority of which is based on in
      vitro diffusion cell studies. The specific experimental setup of such studies may
      skew the obtained results, which is rarely discussed in the context of CD
      studies. Thus, the aim of this work was to conduct a systematic in vitro
      investigation of the permeation enhancement potential of gamma-CD on a steroidal
      drug from a nanoemulsion. The role of critical diffusion cell parameters such as
      the dose of application, occlusive conditions, the nature of the receptor medium
      and the skin thickness were investigated. The results showed that significantly
      enhanced skin permeation rates of fludrocortisone acetate were indeed caused by
      1% (w/w) of gamma-CD at both finite and infinite dose conditions. At 0.5% (w/w)
      of gamma-CD, significant enhancement was only achieved at infinite dose
      application. Additional in vitro tape stripping experiments confirmed these
      tendencies, but the observed effects did not reach statistical significance. It
      may be concluded that the full permeation enhancement potential of the CD as
      observed in the Franz-cell setup can only be realised at infinite dose conditions
      while preserving the formulation structure.

PMID- 22155411
TI  - Design of a pediatric oral formulation with a low proportion of
      hydrochlorothiazide.
AB  - It is a normal pediatric practice in community and hospital pharmacies to prepare
      a new drug formulation when no commercial forms of it are available. Any dose or
      stability control is usually done for these types of compounding formulations due
      to the effort which means to develop these types of tests in pharmacies. We have
      studied five different hydrochlorothiazide oral formulations prepared with
      traditional compounding techniques in pharmacies to treat heart failure and
      edemas in babies. A Standard Operating Procedure (SOP) was done for every
      suspension. After the strictly monitoring of the SOP, every suspension was
      subjected to quality control tests (pH, particle size, viscosity, dose content
      and stability). There is only one studied formulation that guarantees the correct
      dose administering and stability after 3 weeks stored at 5  degrees C and light
      protected. Both, the percentage of wetting agent and the viscosity of the
      suspensor vehicle in this formulation make the correct dose administering
      possible after the formulation is shaken.

PMID- 22155410
TI  - Functionalized (poly(E-caprolactone))2-poly(ethylene glycol) nanoparticles with
      grafting nicotinic acid as drug carriers.
AB  - Nicotinic acid was grafted on (poly(E-caprolactone))(2)-poly(ethylene glycol)
      copolymers that were used for the preparation of nanoparticles with the
      objectives to monitor particle size and to optimize the drug loading capacity as
      well as the release profile of the particles. Increasing amounts of grafting
      nicotinic acid increased the particle size as a result of an enhanced
      hydrophobicity of the copolymer. Ibuprofen and indomethacin with two different
      molecular characteristics were selected as model drugs to be bound to the
      nanoparticles. The presence of grafting nicotinic acid enhanced the loading
      capacity for both drugs compared to the nanoparticles without nicotinic acid.
      However, no correlation between amount of grafting nicotinic acid and loading
      capacity was observed. The release characteristic of both drugs was fitted to the
      Higuchi model indicating Fickian diffusion. The release characteristic of
      indomethacin mainly depended on the crystalline property of the copolymer whereas
      that of ibuprofen was additionally influenced by the hydrogen bonding between
      drug and grafted copolymer.

PMID- 22155412
TI  - Lipomer of doxorubicin hydrochloride for enhanced oral bioavailability.
AB  - The present study discusses design of doxorubicin hydrochloride (Dox) loaded
      lipid based nanocarrier (LIPOMER) for oral delivery. High entrapment (>90 %) and
      high loading (38.11 +/- 0.37 %w/w) of hydrophilic Dox in lipid nanocarrier of
      polyglyceryl-6-distearate was achieved using poly(methyl vinyl ether-co-maleic
      anhydride) (Gantrez AN 119) and a modified nanoprecipitation method. Dox-LIPOMER
      revealed nanosize (314 +/- 16.80 nm) and negative zeta potential (-25.00 +/- 2.41
      mV). Dox-LIPOMER exhibits sustained release in vitro and was influenced by ionic
      strength of dissolution medium. DSC and XRD studies suggested amorphous nature of
      Dox in LIPOMER. TEM revealed spherical morphology of Dox-LIPOMER. Dox-LIPOMER was
      stable up to 12 months at 25  degrees C/60 % RH. A 384 % enhancement in oral
      bioavailability compared to Dox solution was observed following Dox-LIPOMER
      administration at 10 mg/kg body weight. Superoxide dismutase (SOD), catalase
      (CAT) and malondialdehyde (MDA) assay data of heart and kidney tissues of rats
      treated with Dox-LIPOMER were comparable with untreated rats. Dox-LIPOMER
      represents a potential safe drug delivery system for oral administration.

PMID- 22155413
TI  - A quality by design (QbD) case study on liposomes containing hydrophilic API: II.
      Screening of critical variables, and establishment of design space at laboratory
      scale.
AB  - Two statistical designs were used in this case study as part of an investigation
      into the feasibility and the advantages of applying QbD concepts to liposome
      based complex parenteral controlled release systems containing a hydrophilic
      active pharmaceutical ingredient (API). The anti-viral drug tenofovir was used as
      a model compound. First design (Plackett-Burman) was used to screen eight high
      risk variables obtained from risk analysis and assess their impact on liposome
      characteristics (drug encapsulation efficiency, particle size, and physical
      stability). It was discovered that out of eight high-risk variables only lipid
      and drug concentration had significant effects on the drug encapsulation
      efficiency. This allowed the use of a central composite design (CCD) (with more
      predictive capability) to fully elucidate the relationship between lipid
      concentration, drug concentration and encapsulation efficiency. On comparing the
      CCD model generated response surface with additional data points, the accuracy
      and robustness of the model was confirmed. Using this developed model, the design
      space for tenofovir liposomes preparation has been established in a laboratory
      setting, within which the preparation variability is minimized. With regard to
      sample storage stability, it was shown that at 4 degrees C the prepared tenofovir
      liposomes, dispersed in aqueous phase, achieved stability for at least 2 years.
      These principles can be applied to liposomes containing other hydrophilic APIs,
      and can provide time and cost saving to industrial formulation scientists, and
      result in a more robust liposome preparation process.

PMID- 22155414
TI  - Physicochemical properties and skin permeation of Span 60/Tween 60 niosomes of
      ellagic acid.
AB  - Ellagic acid (EA) is a potent antioxidant phytochemical substance which has
      limitation to use due to its poor biopharmaceutical properties, low solubility
      and low permeability. The aim of the present study was to develop niosomal
      formulations obtained from the mixture of Span 60 and Tween 60 that could
      encapsulate EA for dermal delivery. The EA-loaded niosomes were prepared with
      1:0, 2:1, 1:1, 0:1 Span 60 and Tween 60, using polyethylene glycol 400 (PEG 400),
      propylene glycol (PG) or methanol (MeOH) as a solubilizer. The influence of
      formulations on vesicle size, entrapment efficiency and stability of EA-loaded
      niosomes was investigated. It was found that all ratios of surfactants could
      produce EA-loaded niosomes when using 15% (v/v) PG, 15% (v/v) PEG 400 or 20%
      (v/v) MeOH. The niosomes were spherical multilamellar vesicles showing the
      localization of EA in the vesicles. The vesicle sizes of the niosomes after
      extrusion were 124-752 nm with PI less than 0.4. The percentages of entrapment
      efficiency (% E.E.) of all EA-loaded niosomes varied between 1.35% and 26.75%
      while PEG 400 niosomes gave the highest % E.E. The most stable and highest
      entrapped formulation was 2:1 Span 60 and Tween 60 niosomes. Additionally, the in
      vitro skin permeation revealed that penetration of EA from the niosomes depended
      on vesicle size, the amount of EA entrapped and the added solubilizers which
      could act as a permeation enhancer. From skin distribution study, the EA-loaded
      niosomes showed more efficiency in the delivery of EA through human epidermis and
      dermis than EA solution. The results indicated that the Span 60 and Tween 60
      niosomes may be a potential carrier for dermal delivery of EA.

PMID- 22155415
TI  - Do uterine risk factors or lymph node metastasis more significantly affect
      recurrence in patients with endometrioid adenocarcinoma?
AB  - OBJECTIVES: Controversy continues over the importance of lymph node (LN) status
      in treating and predicting recurrence in endometrial cancer. Several predictive
      models are available which use uterine factors to stratify risk groups. Our
      objective was to determine how LN status affects recurrence and survival compared
      to uterine factors alone. METHODS: A retrospective review was performed of
      patients undergoing complete surgical staging for clinical stage 1 endometrioid
      adenocarcinoma of the uterus. Patients were assessed based on PORTEC 1 high
      intermediate risk (H-IR) criteria (2 factors : age>60, grade 3, >50% DOI), GOG-99
      H-IR criteria (age >70+1 factor, age 50-70+2 factors, any age +3 factors: grade 2
      or 3, LVSI, >50% DOI), and PORTEC 2 criteria. Rates of nodal involvement,
      recurrence rates, PFS, and OS were compared. RESULTS: We identified 352 clinical
      stage I patients with positive LN in 24% (87). 175 patients met PORTEC 1
      eligibility and 66 met H-IR criteria. Rates of LN positivity were similar among
      groups (18.4% vs 19.7%, p=0.83) but recurrence rates were dissimilar (7.4% vs
      27.3%, p=0.0004). Only 93 met PORTEC 2 criteria for treatment with no association
      between LN status, recurrence, and eligibility. 188 patients met H-IR eligibility
      criteria for GOG-99 with LN positive and recurrence rates higher in the H-IR
      group compared to GOG-99 eligible (34.6% vs 16.3%, p=0.0004, 28.3% vs. 10.6%,
      p=0.0002). CONCLUSIONS: Patients with H-IR disease based on uterine
      characteristics alone have substantial risk of nodal involvement. Knowledge of LN
      status may better define risk, prognosis, and postoperative treatment.

PMID- 22155416
TI  - Trends in treatment of advanced epithelial ovarian cancer in the Medicare
      population.

PMID- 22155417
TI  - Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by
      comparison to the established marker CA125.
AB  - OBJECTIVE: Evaluate and compare the effectiveness of CA125, HE4, Mesothelin and
      MMP7 marker levels to monitor ovarian cancer patients after surgery and
      chemotherapy. Evaluate the lead time of a rise of marker levels before
      recurrence. METHODS: The study consists of 23 patients with advanced stage
      ovarian/fallopian tube cancer. Blood was drawn after front line surgery and
      chemotherapy treatment and at 3 month intervals thereafter. One patient had
      chemoresistant disease, two patients remained in remission and 20 patients had
      recurring disease and were used for marker evaluation. RESULTS: In five patients
      HE4 was the only marker to elevate before recurrence with a lead time of up to
      41/2 months including one patient who did not have a CA125 response at all. In a
      further two patients, HE4 increased before CA125 did. In four of these seven
      patients, HE4 levels were consistently at or above threshold during remission
      when both CA125 and imaging results were negative. MMP7 elevated before
      recurrence in one patient who was negative for the other markers. Mesothelin
      elevated in two patients who were also positive for CA125 and HE4. CONCLUSIONS:
      HE4 can predict ovarian cancer recurrence earlier than CA125 and it can be
      elevated in patients that do not express CA125 at sufficient levels to make a
      clinical decision. MMP7 and Mesothelin have lower potential as markers for
      ovarian cancer recurrence to complement CA125. A failure of HE4 levels to
      normalize at completion of standard therapy may indicate a poor prognosis.

PMID- 22155418
TI  - ACR Appropriateness Criteria(r) role of adjuvant therapy in the management of
      early stage cervical cancer.
AB  - OBJECTIVE: The use of adjuvant treatment(s) following initial hysterectomy and
      retroperitoneal nodal harvesting of patients with clinical stage I and II
      cervical carcinoma is (are) presently based on the pathological assessment of
      surgical specimens. This report sought to delineate further the clinical
      application of potential therapeutic interventions and associated follow-up
      investigations of this patient cohort. METHODS: The American College of Radiology
      (ACR) Appropriateness Criteria are evidence-based guidelines for specific
      clinical conditions that are reviewed every two years by a multidisciplinary
      expert panel. The guideline development and review include an extensive analysis
      of current medical literature from peer reviewed journal and the application of a
      well-established consensus methodology (modified Delphi) to rate appropriateness
      of imaging and treatment procedures by the panel. In those instances where
      evidence is lacking or not definitive, expert opinion may be used to recommend
      imaging or treatment. RESULTS: From this process, 5 unique clinical variants were
      developed. These scenarios pertained to options of adjuvant radiation therapy and
      chemotherapy, methods of delivery of radiotherapy to optimize target volume
      coverage while simultaneously minimizing radiation exposure of adjacent healthy
      organs, and recommendations for patient follow-up care. Group members reached
      consensus of topic ratings in descending order of importance. A risk assessment
      breakdown was established to highlight the most likely indications for adjuvant
      treatment(s). CONCLUSION: This assembly by the ACR of physicians involved in the
      management of patients with early stage cervical cancer was able to describe
      appropriateness criteria to aid other practitioners in selecting reasonable
      implementation of postoperative therapies and subsequent surveillance studies.
      These guidelines await further validation and refinement by both current and
      future prospectively randomized clinical studies regarding this patient
      population.

PMID- 22155420
TI  - Pulsed acoustic cellular expression as a protective therapy against I/R injury in
      a cremaster muscle flap model.
AB  - BACKGROUND: Tissue ischemia and reperfusion (I/R) affects blood flow restoration
      and oxygen delivery to the damaged tissues contributing to tissue morbidity and
      microcirculatory compromise. Pulsed acoustic cellular expression (PACE)
      technology is known to support tissue neovascularization. The aim of this study
      was to test PACE conditioning mechanism of action on microcirculatory
      hemodynamics in ischemia-reperfusion injury model. METHODS: 34 rat cremaster
      muscle flaps were monitored under intravital microscopy system in 4 experimental
      groups: 1) non-ischemic controls (n=10), 2) 5h ischemia without conditioning
      (n=8), 3) pre-ischemic (5h) PACE conditioning (n=8), 4) post-ischemic (5h) PACE
      conditioning (n=8). Standard microcirculatory hemodynamics of RBC velocity,
      vessel diameters and functional capillary perfusion were recorded for 2h after
      I/R. Immunohistochemistry assessed expression of proangiogenic factors: VEGF and
      vWF, whereas real-time PCR assessed proangiogenic (VEGF, eNOS) and
      proinflammatory factors (iNOS; chemokines: CCL2, CXCL5 and chemokine receptor
      CCR2). RESULTS: Pre-ischemic PACE conditioning (group 3) resulted in increased
      RBC velocity of second (A-2) and third order arterioles (A-3) and venule (V-1) by
      40%, 15% and 24% respectively comparing to ischemic group without conditioning
      (p<0.05). Post-ischemic PACE conditioning (group 4) revealed: 1) increase in RBC
      velocity in second (A-2) and third order arterioles (A-3) by 65% and 31%
      respectively comparing to ischemia without conditioning (group 2), 2) 33%
      increase in first order arterioles diameter (A-1) (p<0.05) compared to ischemic
      controls, 3) 21% increase in number of functional capillaries compared to
      ischemia without conditioning (group 2) (P<0.05). Immunostaining assays showed
      that PACE postconditioning up-regulated proangiogenic factors vWF and VEGF
      protein expression. This correlated with increased gene expression of VEGF (up to
      180%). In contrast, gene expression of proinflammatory factors (iNOS, CCL2,
      CXCL5) decreased compared to ischemic controls. Pre-ischemic PACE conditioning
      decreased gene expression of proinflammatory chemokines (CCL2 and CXCL5),
      compared to ischemic controls without conditioning. CONCLUSIONS: As expected 5h
      ischemia resulted in deterioration of microcirculatory hemodynamics confirmed by
      decreased vessels diameters and RBC velocities. This was alleviated by pre- and
      post-ischemic PACE conditioning which improved functional capillary density and
      stimulated angiogenesis as confirmed by up-regulated VEGF expression.
      Furthermore, post-ischemic PACE conditioning correlated with decreased expression
      of early proinflammatory factors (iNOS, CCL2, CXCL5). Both types of PACE
      conditioning ameliorated deleterious effect of ischemia-reperfusion injury on
      microcirculatory hemodynamics of muscle flaps.

PMID- 22155421
TI  - Effects of cell-free layer formation on NO/O2 bioavailability in small
      arterioles.
AB  - We developed a new time-dependent computational model for coupled NO/O(2)
      transport in small arterioles that incorporates potential physiological responses
      (temporal changes in NO scavenging rate and O(2) partial pressure in blood lumen
      and NO production rate in endothelium) to the temporal cell-free layer width
      variations. Two relations between wall shear stress (WSS) and NO production rate
      based on the linear and sigmoidal functions were considered in this simulation
      study. The cell-free layer data used for the simulation were acquired from
      arteriolar flows (D=48.3 +/- 1.9 MUm) in the rat cremaster muscles under normal
      flow conditions (WSS=3.4-5.6 Pa). For both cases of linear and sigmoidal
      relations, temporal layer width variations were found to be capable of
      significantly enhancing NO bioavailability and this effect was more pronounced in
      the latter (P<0.0005) than the former (P<0.005). In contrast, O(2)
      bioavailability in the arteriolar wall was not considerably altered by the
      temporal layer width variations, irrespective of the relation. Prominent
      enhancement (P<0.005) of soluble guanylyl cyclase (sGC) activation in the smooth
      muscle by the temporal layer width variations were predicted for both relations.
      The extent of sGC activation was generally lower (P<0.01) in the case of the
      sigmoidal relation than that of the linear relation, suggesting a lesser tendency
      for arterioles to dilate with the former.

PMID- 22155419
TI  - Formation of P450 . P450 complexes and their effect on P450 function.
AB  - Cytochromes P450 (P450) are membrane-bound enzymes that catalyze the
      monooxygenation of a diverse array of xenobiotic and endogenous compounds. The
      P450s responsible for foreign compound metabolism generally are localized in the
      endoplasmic reticulum of the liver, lung and small intestine. P450 enzymes do not
      act alone but require an interaction with other electron transfer proteins such
      as NADPH-cytochrome P450 reductase (CPR) and cytochrome b(5). Because P450s are
      localized in the endoplasmic reticulum with these and other ER-resident proteins,
      there is a potential for protein-protein interactions to influence P450 function.
      There has been increasing evidence that P450 enzymes form complexes in the ER,
      with compelling support that formation of P450 . P450 complexes can significantly
      influence their function. Our goal is to review the research supporting the
      formation of P450 . P450 complexes, their specificity, and how drug metabolism
      may be affected. This review describes the potential mechanisms by which P450s
      may interact, and provides evidence to support each of the possible mechanisms.
      Additionally, evidence for the formation of both heteromeric and homomeric P450
      complexes are reviewed. Finally, direct physical evidence for P450 complex
      formation in solution and in membranes is summarized, and questions directing the
      future research of functional P450 interactions are discussed with respect to
      their potential impact on drug metabolism.

PMID- 22155422
TI  - Phylogenetic relationships in Myrceugenia (Myrtaceae) based on plastid and
      nuclear DNA sequences.
AB  - Myrceugenia is a genus endemic to South America with a disjunct distribution: 12
      species occurring mainly in central Chile and approximately 25 in southeastern
      Brazil. Relationships are reconstructed within Myrceugenia from four plastid
      markers (partial trnK-matK, rpl32-trnL, trnQ-5'rps16 and rpl16) and two ribosomal
      nuclear regions (ETS and ITS) using maximum parsimony and Bayesian analyses.
      Relationships inferred previously from morphological data are not completely
      consistent with those from molecular data. All molecular analyses support the
      hypothesis that Myrceugenia is monophyletic, except for M. fernadeziana that
      falls outside the genus. Chilean species and Brazilian species form two separate
      lineages. Chilean species form three early diverging clades, whereas Brazilian
      species are a strongly supported monophyletic group in a terminal position. Least
      average evolutionary divergence, low resolution, short branches, and high species
      diversity found in the Brazilian clade suggest rapid radiation. Geographical
      distributions and phylogenetic reconstructions suggest that extant Myrceugenia
      species arose in northern Chile followed by colonization southward and finally to
      the Juan Fernandez Islands and southeastern Brazil.

PMID- 22155423
TI  - Exploring diversity in cryptorhynchine weevils (Coleoptera) using distance-,
      character- and tree-based species delineation.
AB  - Species boundaries are studied in a group of beetles, the western Palaearctic
      Cryptorhynchinae. We test for congruence of 'traditionally' identified
      morphospecies with species inferred through parsimony networks, distance-based
      clustering and the ultrametric tree-based generalized mixed yule-coalescent
      (GMYC) approach. For that purpose, we sequenced two variable fragments of
      mitochondrial DNA (CO1 and 16S) for a total of 791 specimens in 217 species of
      Cryptorhynchinae. Parsimony networks, morphology-calibrated distance clusters and
      the different tree-based species inferences all achieved low congruence with
      morphospecies, at best 60%. Although the degree of match with morphospecies was
      often similar for the different approaches, the composition of clusters partially
      varied. A barcoding gap was absent in morphospecies-oriented distances as well as
      for GMYC species clusters. This demonstrates that not only erroneous taxonomic
      assignments, incomplete lineage sorting, hybridization, or insufficient sampling
      can compromise distance-based identification, but also differences in speciation
      rates and uneven tree structure. The initially low match between morphospecies
      and the different molecular species delineation methods in this case study shows
      the necessity of combining the output of various methods in an integrative
      approach. Thereby we obtain an idea about the reliability of the different
      results and signals, which enables us to fine-tune sampling, delineation
      technique and data collection, and to identify species that require taxonomic
      revision.

PMID- 22155424
TI  - Low environmental levels of fluoxetine induce spawning and changes in endogenous
      estradiol levels in the zebra mussel Dreissena polymorpha.
AB  - The pharmaceutical fluoxetine, a selective serotonin reuptake inhibitor (SSRI),
      is often detected in municipal wastewater treatment plant effluents and surface
      waters within the ng/l range. There is, however, insufficient research evaluating
      potential hazards of fluoxetine in aquatic organisms at environmentally relevant
      concentrations. Taking into account that several SSRIs (fluoxetine, fluvoxamine)
      act as spawning inducers in bivalves, this study aimed at investigating the
      effects of fluoxetine exposure in the zebra mussel (Dreissena polymorpha) by
      assessing its potential to induce spawning at environmentally relevant
      concentrations (20 and 200 ng/l), as well as alterations of endogenous levels of
      testosterone and estradiol. Histological analyses of female and male gonads
      showed a concentration dependent decrease of oocyte and spermatozoan density,
      with a reduction in the number of oocytes per follicle of 40-70%, and
      spermatozoan density of 21-25%, relative to controls, following exposure to 20
      and 200 ng/l of fluoxetine for 6 days, respectively. There was also a significant
      increase (1.5-fold) in the endogenous level of esterified estradiol in organisms
      exposed to 200 ng/l fluoxetine. Overall, the study shows that exposure to low
      levels of fluoxetine may effectively induce gamete liberation in the zebra mussel
      as well as alter endogenous levels of estradiol, and evidences the need of
      further investigating the potential of fluoxetine to alter the endocrine system
      of molluscs at environmentally relevant concentrations.

PMID- 22155425
TI  - Persistent effects on adult swim performance and energetics in zebrafish
      developmentally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) remains a potent and persistent
      toxicant in aquatic environments, causing lethal developmental deformities in
      fish. However, few studies have examined sublethal or persistent effects of
      developmental TCDD exposure and none have examined its effects on swimming
      capabilities in sub-adult fish. The objective of the current study was to examine
      whether effects of TCDD exposure during the critical period of cardiovascular
      development (2-4 days post fertilization) on swim performance, triglyceride
      stores and cardiovascular deformities would persist until adulthood in zebrafish.
      Zebrafish larvae were exposed between 48 and 96 h post fertilization to 1, 0.1,
      0.01 ng/L TCDD or DMSO control (0.005%), then raised in clean water for 90 days.
      Despite having equal survivability, no significant increase in gross deformities
      and no change in cytochrome P450 1A (CYP1A) activity was observed, while critical
      swimming speed and dorsal aorta diameter were significantly decreased in TCDD
      exposed fish at 90 days. Furthermore, whole body triglycerides were significantly
      elevated in TCDD-exposed fish both before and after swim testing. Therefore
      sublethal TCDD exposure during zebrafish development caused a persistent decrease
      in swim endurance. The cause of this persistent decrease in swim endurance is not
      known, but may be related to behavioral adaptations limiting swimming
      capabilities, failure to mobilize triglyceride stores, vascular deformities
      limiting blood flow to the periphery, or a combination of these factors.

PMID- 22155426
TI  - Immune responses and ultrastructural changes of hemocytes in freshwater crab
      Sinopotamon henanense exposed to elevated cadmium.
AB  - Cadmium (Cd) is one of the most toxic heavy metals that can impact immunological
      parameters in aquatic animals. To investigate the immunotoxicity and
      ultrastructural changes of hemocytes, specimens of Sinopotamon henanense were
      exposed to different concentrations of cadmium and the differences in immunologic
      parameters between Cd exposure groups and control groups were investigated. Total
      hemocyte count (THC) in Cd-exposure groups were decreased significantly when
      compared with the control groups, especially in the groups treated with higher Cd
      concentrations and longer exposure time, while no significant differences were
      observed in the proportions of the three types of hemocytes. Phenoloxidase (PO)
      activities were significantly higher in Cd-exposure groups than the control
      groups. Superoxide dismutase (SOD) activities gradually increased in 7.25 and
      14.5 mg L-1 Cd groups, but in other higher Cd groups, they showed first increase
      and following decrease with the exposure time prolonged. Acid phosphatase (ACP)
      activities were induced at 48 h, and then decreased, while alkaline phosphatase
      (AKP) activities increased gradually until 96 h. Electron microscopic results
      showed that nucleus, mitochondria and rough endoplasm recutulum (rER) of three
      types of hemocytes were sensitive to acute Cd toxicity. In Cd-exposed groups,
      chromatin condensation, nucleus deformation and nucleus envelope rupture were
      noted. Additionally, mitochondrial dilation and rER degranulation were observed
      in Cd-treated crabs. These results suggested that immune response and organelles
      of hemocyte of S. henanense were impacted by Cd exposure, and the changes of
      these immunologic parameters reflect changes in crab immune response capability
      consequent to Cd exposure.

PMID- 22155427
TI  - Disruption of endocrine function in in vitro H295R cell-based and in in vivo
      assay in zebrafish by 2,4-dichlorophenol.
AB  - Chlorophenols in the aquatic environment have been of concern due to their
      potential effects on human and wildlife. In the present study, the endocrine
      disrupting effects of 2,4-dichlorophenol (2,4-DCP) were investigated in vitro and
      in vivo. In the in vitro assay, H295R human adrenocortical carcinoma cells were
      used to determine the potential effects of 2,4-DCP on steroidogenesis. Exposure
      to 0, 0.1, 0.3 or 1.0 mg 2,4-DCP/L resulted in less production of 17beta
      estradiol (E2) and alterations in transcript expressions of genes involved in
      steroidogenesis, including cytochrome P450 (CYP11A, CYP17, CYP19), 3betaHSD,
      17betaHSD and StAR. In the in vivo study, effects of 0, 0.03, 0.1 or 0.3 mg 2,4
      DCP/L on concentrations of steroid hormones in plasma of adult zebrafish (Danio
      rerio) were measured and expression of mRNA of selected genes in hypothalamic
      pituitary-gonadal (HPG) axis and liver were determined. Exposure of zebrafish to
      2,4-DCP resulted in lesser concentrations of E2 accompanied by down-regulation of
      CYP19A mRNA in the females. In males, exposure to 2,4-DCP resulted in greater
      concentrations of testosterone (T) and E2 along with greater mRNA expression of
      CYP17 and CYP19A. The mRNA expression of prostaglandin synthase (Ptgs2) gene,
      which regulates ovulation, was down-regulated in females, but up-regulated in
      males. The hepatic estrogenic receptor (ERalpha and ERbeta) and vitellogenin
      (VTG1 and VTG3) mRNAs were up-regulated in both females and males. The average
      number of eggs spawned was significantly less upon exposure to 2,4-DCP. Exposure
      of adult zebrafish to 2,4-DCP resulted in lesser rates of hatching of eggs. The
      results demonstrated that 2,4-DCP modulates transcription of steroidogenetic
      genes in both H295R cells and in the zebrafish HPG-axis and disrupts
      steroidogenesis, which in turn, can cause adverse effects on reproduction in
      fish.

PMID- 22155428
TI  - A novel DNAseq program for enhanced analysis of Illumina GAII data: a case study
      on antibody complementarity-determining regions.
AB  - High-throughput DNA sequencing technologies are increasingly becoming powerful
      systems for the comprehensive analysis of variations in whole genomes or various
      DNA libraries. As they are capable of producing massive collections of short
      sequences with varying lengths, a major challenge is how to turn these reads into
      biologically meaningful information. The first stage is to assemble the short
      reads into longer sequences through an in silico process. However, currently
      available software/programs allow only the assembly of abundant sequences, which
      apparently results in the loss of highly variable (or rare) sequences or creates
      artefact assemblies. In this paper, we describe a novel program (DNAseq) that is
      capable of assembling highly variable sequences and displaying them directly for
      phylogenetic analysis. In addition, this program is Microsoft Windows-based and
      runs by a normal PC with 700MB RAM for a general use. We have applied it to
      analyse a human naive single-chain antibody (scFv) library, comprehensively
      revealing the diversity of antibody variable complementarity-determining regions
      (CDRs) and their families. Although only a scFv library was exemplified here, we
      envisage that this program could be applicable to other genome libraries.

PMID- 22155429
TI  - Isolation of monobodies that bind specifically to the SH3 domain of the Fyn
      tyrosine protein kinase.
AB  - Fyn is a nonreceptor protein tyrosine kinase that belongs to a highly conserved
      kinase family, Src family kinases. Fyn plays an important role in inflammatory
      processes and neuronal functions. To generate a synthetic affinity reagent that
      can be used to probe Fyn, a phage-display library of fibronectin type III
      monobodies was affinity selected with the Src Homology 3 (SH3) domain of Fyn and
      three binders were isolated. One of the three binders, G9, is specific in binding
      to the SH3 domain of Fyn, but not to the other members of the Src family (i.e.
      Blk, Fgr, Hck, Lck, Lyn, Src and Yes), even though they share 51-81% amino acid
      identity. The other two bind principally to the Fyn SH3 domain, with some cross
      reactivity to the Yes SH3 domain. The G9 binder has a dissociation constant of
      166+/-6nM, as measured by isothermal titration calorimetry, and binds only to the
      Fyn SH3 domain out of 150 human SH3 domains examined in an array. Interestingly,
      although the G9 monobody lacks proline in its randomized BC and FG loops, it
      binds at the same site on the SH3 domain as proline-rich ligands, as revealed by
      competition assays. The G9 monobody, identified in this study, may be used as a
      highly selective probe for detecting and purifying cellular Fyn kinase.

PMID- 22155430
TI  - Development of a Plexor real-time PCR assay for the detection of porcine
      circovirus type 2.
AB  - A novel, real-time PCR system for the detection of porcine circovirus type 2
      (PCV2) was developed. The system employed Plexor technology and detected 10(8)
      10(1) copies per reaction of PCV2 DNA within a recombinant plasmid. The
      examination of clinical material showed consistent diagnostic sensitivity when
      samples contained more than 10(3) viral copies per reaction. Specificity of
      Plexor real-time PCR was confirmed using the porcine viruses PCV1, PRRSV, CSFV,
      TTSuV1 and TTSuV2 employing the melting curve analysis of PCR products. The low
      values of coefficient of variation in the intra- (1.74%) and inter-assay (2.41%)
      analysis suggested that the assay was a highly reproducible. The Plexor real-time
      PCR was compared with three other real-time PCR systems (SYBR Green, TaqMan, LUX)
      with conclusion that it can be used as a method of choice for the detection and
      quantitation of PCV2.

PMID- 22155431
TI  - Osteoarthritis-like changes in the heterozygous sedc mouse associated with the
      HtrA1-Ddr2-Mmp-13 degradative pathway: a new model of osteoarthritis.
AB  - OBJECTIVE: To test the hypothesis that the spondyloepiphyseal dysplasia congenita
      (sedc) heterozygous (sedc/+) mouse, a COL2A1 mutant, is a model for the study of
      osteoarthritis (OA) in the absence of dwarfism and to investigate the presence of
      HtrA1, Ddr2, and Mmp-13 and their possible involvement in a universal mechanism
      leading to OA. DESIGN: Whole mount skeletons of adult animals were analyzed to
      determine whether sedc/+ mice exhibit dwarfism. To characterize progression of
      osteoarthritic degeneration over time, knee and temporomandibular joints from
      sedc/+ and wild-type mice were analyzed histologically, and severity of articular
      cartilage degradation was graded using the Osteoarthritis Research Society
      International (OARSI) scoring system. Immunohistochemistry was used to detect
      changes in expression of HtrA1, Ddr2, and Mmp-13 in articular cartilage of knees.
      RESULTS: As previously reported, the sedc/+ skeleton morphology was
      indistinguishable from wild type, and skeletal measurements revealed no
      significant differences. The sedc/+ mouse did, however, show significantly higher
      OARSI scores in knee (9, 12 and 18 months) and temporomandibular joints at all
      ages examined. Histological staining showed regions of proteoglycan degradation
      as early as 2 months in both temporomandibular and knee joints of the mutant.
      Cartilage fissuring and erosion were observed to begin between 2 and 6 months in
      temporomandibular joints and 9 months in knee joints from sedc/+ mice.
      Immunohistochemistry of mutant knee articular cartilage showed increased
      expression of HtrA1, Ddr2, and Mmp-13 compared to wild type, which upregulation
      preceded fibrillation and fissuring of the articular surfaces. CONCLUSIONS: With
      regard to skeletal morphology, the sedc/+ mouse appears phenotypically normal but
      develops premature OA as hypothesized. We conclude that the sedc/+ mouse is a
      useful model for the study of OA in individuals with overtly normal skeletal
      structure and a predisposition for articular cartilage degeneration.

PMID- 22155432
TI  - Putting proteins in their place: palmitoylation in Huntington disease and other
      neuropsychiatric diseases.
AB  - Post-translational modification of proteins by the lipid palmitate is critical
      for protein localization and function. Palmitoylation is regulated by the
      opposing enzymes palmitoyl acyltransferases (PATs) and acyl protein
      thioesterases, which add and remove palmitate from proteins, respectively.
      Palmitoylation is particularly important for a number of processes including
      neuronal development and synaptic activity in the central nervous system.
      Dysregulated palmitoylation contributes to neuropsychiatric disease. In total six
      PATs (HIP14, HIP14L, ZDHHC8, ZDHHC9, ZDHHC12, and ZDHHC15) and one thioesterase
      (PPT1) have been implicated in Huntington disease (HD), Alzheimer disease,
      schizophrenia, mental retardation, and infantile and adult onset forms of
      neuronal ceroid lipofuscinosis. Currently there is no genetic link between PATs
      and Alzheimer disease pathogenesis but palmitoylation of amyloid precursor
      protein-processing enzyme, gamma-secretase, influences beta-amyloid generation.
      Several lines of evidence point to a role for palmitoylation by HIP14 in the
      pathogenesis of HD; HIP14 is dysfunctional in the presence of the HD mutation and
      Hip14-deficient mice develop features of HD. Wildtype huntingtin (the protein
      mutated in HD) enhances the PAT activity of HIP14 and mutant HTT interacts less
      with HIP14. Therefore, it may be that loss of the positive modulation of HIP14
      activity due to reduced interaction with huntingtin is important in the disease
      mechanism. Preliminary evidence suggests a closely related PAT to HIP14, HIP14L,
      may also play a role in the pathogenesis of HD. In order to design rational
      therapeutic approaches to restore palmitoylation in neuropsychiatric disease, it
      will be critical to better understand the relationships between PATs and
      thioesterases with their regulators and substrates.

PMID- 22155433
TI  - Development of quantitative enzymatic method and its validation for the assay of
      glucose in human serum.
AB  - OBJECTIVE: To develop a simple, rapid, sensitive and affordable assay method for
      the determination of glucose in blood samples using a novel approach. DESIGN AND
      METHODS: A spectrophotometric method for glucose quantification in human serum
      samples based on self-coupling of activated 2,5-dimethoxyaniline (DMA) in the
      presence of peroxidase (POD)/glucose oxidase (GOD) and H(2)O(2) is described.
      H(2)O(2) generated in situ by catalytic reaction between GOD and glucose,
      activates DMA in the presence of POD to form a green-colored product, which has a
      strong absorption at lambda(max)=740 nm at room temperature (30 degrees C) in a
      100 mmol/L acetate/acetic acid buffer of pH 4.2. RESULTS: The linearity ranges
      for the quantification of glucose by rate and one-time detection method are 0.017
      0.740 and 0.017-0.478 mmol/L, respectively. Within-day and day-to-day precision
      were 0.98-1.4% (n=10) and 1.33-2.89% (n=15), respectively. Glucose recoveries
      ranged from 96.6 to 102%, indicating minimal interference by commonly present
      interferants in serum samples. Accuracy results were between 90 and 102%. The
      detection and quantification limits of glucose were 2.376 and 7.923 MUmol/L,
      respectively. The proposed method has good correlation coefficient of 0.999 with
      the enzymatic kit method. CONCLUSIONS: This is a rapid and convenient method to
      determine serum glucose using simple spectrophotometer with excellent recovery
      and minimal interference by interferants in serum samples with low detection
      limit. Therefore, this method can be considered for adoption by the clinical
      diagnostic laboratories.

PMID- 22155434
TI  - An unusual case of abdominal arterial thrombosis in a young woman using
      desmopressin.
AB  - We report an unusual case of severe abdominal arterial thrombosis in a young
      woman using oral desmopressin. Only a few cases with cerebrovascular accidents
      and coronary syndromes have been described so far, which could be attributed to
      intravenous administration of desmopressin. Because extensive diagnostic and
      laboratory investigations for (un)common coagulation disorders could not identify
      an alternative explanation associated with arterial thrombosis, we hypothesise
      that desmopressin in an oral dose of at least 200 ug once daily must have been
      sufficient to cause this dramatic vascular complication. Supportive of our
      hypothesis, we found remarkably high levels of factor VIII activity, Von
      Willebrand factor (vWF) antigen and vWF ristocetin cofactor activity (268%, 740%,
      590% respectively). To the best of the authors' knowledge, this is the first
      report suggesting a relationship between oral desmopressin use and life
      threatening abdominal arterial thrombosis.

PMID- 22155436
TI  - Childhood obesity can be prevented, says Cochrane.

PMID- 22155435
TI  - Effect of beta blockade on natriuretic peptides and copeptin in elderly patients
      with heart failure and preserved or reduced ejection fraction: results from the
      CIBIS-ELD trial.
AB  - BACKGROUND: We sought to investigate the effect of beta-blocker (BB) up-titration
      on serum levels of NT-proBNP and copeptin in patients with heart failure (HF)
      with reduced (HFREF) or preserved ejection fraction (HFPEF). METHODS: Serial
      measurements of NT-proBNP and copeptin were obtained after initiation of BB up
      titration in 219 elderly patients with HFREF or HFPEF. RESULTS: After initial
      increasing trend of NT-proBNP at 6 weeks in HFREF patients, there was a
      subsequent decrease at 12 weeks of BB treatment up-titration (p=0.003), while no
      difference was found compared to baseline levels. In contrast to NT-proBNP, there
      was a continuous decreasing trend of copeptin in HFREF patients (at 12 weeks:
      p=0.026). In HFPEF patients, NT-proBNP significantly decreased (p=0.043) compared
      to copeptin after 12 weeks of BB up-titration. CONCLUSIONS: After 12 weeks of BB
      optimization copeptin might reflect successful up-titration faster than NT-proBNP
      in HFREF, while the opposite was found in patients with HFPEF.

PMID- 22155437
TI  - Child health is under threat from NHS reforms, says report.

PMID- 22155438
TI  - Intrauterine exposure to thiopurines.

PMID- 22155440
TI  - GABA(A) and dopamine receptors in the nucleus accumbens shell differentially
      influence performance of a water-reinforced progressive ratio task.
AB  - Several authors have shown that injections of the GABA(A) agonist muscimol into
      the medial shell region of the nucleus accumbens (AcbSh) result in large
      increases in food, but not water, intake. In previous studies we demonstrated
      that intra-AcbSh injections of either muscimol or of the indirect dopamine
      agonist amphetamine increase response output on a food-reinforced progressive
      ratio schedule. In the current experiment we extended these observations by
      examining the effects of muscimol and amphetamine injections on the performance
      of a water-reinforced progressive ratio task in mildly deprived animals. We found
      that muscimol did not affect the number of responses made in the water-reinforced
      task, even though a marked increase in responding was observed after amphetamine.
      Muscimol did, however, significantly increase food intake in the same animals.
      The results suggest that the enhancing effects of intra-AcbSh muscimol differ
      from those of amphetamine in that they are selective for food-reinforced
      behaviors.

PMID- 22155441
TI  - The effect of the Asp175Asn and Glu180Gly TPM1 mutations on actin-myosin
      interaction during the ATPase cycle.
AB  - Hypertrophic cardiomyopathy (HCM), characterized by cardiac hypertrophy and
      contractile dysfunction, is a major cause of heart failure. HCM can result from
      mutations in the gene encoding cardiac alpha-tropomyosin (TM). To understand how
      the HCM-causing Asp175Asn and Glu180Gly mutations in alpha-tropomyosin affect on
      actin-myosin interaction during the ATPase cycle, we labeled the SH1 helix of
      myosin subfragment-1 and the actin subdomain-1 with the fluorescent probe N
      iodoacetyl-N'-(5-sulfo-1-naphtylo)ethylenediamine. These proteins were
      incorporated into ghost muscle fibers and their conformational states were
      monitored during the ATPase cycle by measuring polarized fluorescence. For the
      first time, the effect of these alpha-tropomyosins on the mobility and rotation
      of subdomain-1 of actin and the SH1 helix of myosin subfragment-1 during the ATP
      hydrolysis cycle have been demonstrated directly by polarized fluorimetry. Wild
      type alpha-tropomyosin increases the amplitude of the SH1 helix and subdomain-1
      movements during the ATPase cycle, indicating the enhancement of the efficiency
      of the work of cross-bridges. Both mutant TMs increase the proportion of the
      strong-binding sub-states, with the effect of the Glu180Gly mutation being
      greater than that of Asp175Asn. It is suggested that the alteration in the
      concerted conformational changes of actomyosin is likely to provide the
      structural basis for the altered cardiac muscle contraction.

PMID- 22155442
TI  - Impaired hippocampal glucoregulation in the cannabinoid CB1 receptor knockout
      mice as revealed by an optimized in vitro experimental approach.
AB  - Several techniques exist to study the rate of glucose uptake and metabolism in
      the brain but most of them are not sufficiently robust to permit extensive
      pharmacological analysis. Here we optimized an in vitro measurement of the
      simultaneous accumulation of the metabolizable and non-metabolizable (3)H and
      (14)C d-glucose analogues; permitting convenient large-scale studies on glucose
      uptake and metabolism in brain slices. Next, we performed an extensive
      pharmacological characterization on the putative glucoregulator role of the
      endocannabinoid system in the hippocampal slices of the rat, and the wild-type
      and the CB(1) cannabinoid receptor (CB(1)R) knockout mice. We observed that (3)H
      3-O-methylglucose is a poor substrate to measure glucose uptake in the
      hippocampus. (3)H-2-deoxyglucose is a better substrate but its uptake is still
      lower than that of (14)C-U-d-glucose, from which the slices constantly metabolize
      and dissipate (14)C atoms. Thus, uptake and the metabolism values are not to be
      used as standalones but as differences between a control and a treatment. The
      CB(1)R knockout mice exhibited ~10% less glucose uptake and glucose carbon atom
      dissipation in comparison with the wild-type mice. This may represent congenital
      defects as acute treatments of the rat and mouse slices with cannabinoid
      agonists, antagonists and inhibitors of endocannabinoid uptake/metabolism failed
      to induce robust changes in either the uptake or the metabolism of glucose. In
      summary, we report here an optimized technique ideal to complement other
      metabolic approaches of high spatiotemporal resolution. This technique allowed us
      concluding that CB(1)Rs are at least indirectly involved in hippocampal
      glucoregulation.

PMID- 22155443
TI  - A novel device for the study of somatosensory information processing.
AB  - Current methods for applying multi-site vibratory stimuli to the skin typically
      involve the use of multiple, individual vibrotactile stimulators. Limitations of
      such an arrangement include difficulty with both positioning the stimuli as well
      as ensuring that stimuli are delivered in a synchronized and deliberate manner.
      Previously, we reported a two-site tactile stimulator that was developed in order
      to solve these problems (Tannan et al., 2007a). Due to both the success of that
      novel stimulator and the limitations that were inherent in that device, we
      designed and fabricated a four-site stimulator that provides a number of
      advantages over the previous version. First, the device can stimulate four
      independent skin sites and is primarily designed for stimulating the digit tips.
      Second, the positioning of the probe tips has been re-designed to provide better
      ergonomic hand placement. Third, the device is much more portable than the
      previously reported stimulator. Fourth, the stimulator head has a much smaller
      footprint on the table or surface where it resides. To demonstrate the capacity
      of the device for delivering tactile stimulation at four independent sites, a
      finger agnosia protocol, in the presence and absence of conditioning stimuli, was
      conducted on seventeen healthy control subjects. The study demonstrated that with
      increasing amplitudes of vibrotactile conditioning stimuli concurrent with the
      agnosia test, inaccuracies of digit identification increased, particularly at
      digits D3 and D4. The results are consistent with prior studies that implicated
      synchronization of adjacent and near-adjacent cortical ensembles with
      conditioning stimuli in impacting TOJ performance (Tommerdahl et al., 2007a,b).

PMID- 22155444
TI  - Scleral mechanics: comparing whole globe inflation and uniaxial testing.
AB  - The purpose of this study was to assess fundamental differences between the
      mechanics of the posterior sclera in paired eyes using uniaxial and whole globe
      inflation testing, with an emphasis on the relationship between testing
      conditions and observed tissue behavior. Twenty porcine eyes, consisting of
      matched pairs from 10 pigs, were used in this study. Within pairs, one eye was
      tested with 10 cycles of globe pressurization to 150 mmHg (~10* normal IOP) while
      biaxial strains were tracked via an optical system at the posterior sclera. An
      excised posterior strip from the second eye was subjected to traditional uniaxial
      testing in which mechanical hysteresis was recorded from 10 cycles to a peak
      stress of 0.13 MPa (roughly equivalent to the circumferential wall stress
      produced by an IOP of 150 mmHg under the thin-walled pressure vessel assumption).
      For approximately equivalent loads, peak strains were more than twice as high in
      uniaxial tests than in inflation tests. Different trends in the load-deformation
      plots were seen between the tests, including an extended "toe" region in the
      uniaxial test, a generally steeper curve in the inflation tests, and reduced
      variability in the inflation tests. The unique opportunity of being able to
      mechanically load a whole globe under near physiologic conditions alongside a
      standard uniaxially tested specimen reveals the effects of testing artifacts
      relevant to most uniaxially tested soft tissues. Whole globe inflation offers
      testing conditions that significantly alter load-deformation behavior relative to
      uniaxial testing; consequently, laboratory studies of interventions or conditions
      that alter scleral mechanics may greatly benefit from these findings.

PMID- 22155445
TI  - Possible role of dopamine D1-like and D2-like receptors in behavioural activation
      and evaluation of response efficacy in the forced swimming test.
AB  - Based on the different effects of the dopamine D1-like and D2-like receptor
      antagonists SCH 23390 and raclopride on the measures of licking microstructure in
      rats ingesting a sucrose solution, we suggested that the behavioural activation
      of reward-associated responses depends on dopamine D1-like receptor stimulation,
      and its level is updated, or "reboosted", on the basis of a dopamine D2-like
      receptor-mediated evaluation process. The aim of this study was to test this
      hypothesis on the forced swimming test response. The effects of the dopamine D1
      like and D2-like receptor antagonists SCH 23390 (0.01-0.04 mg/kg) and raclopride
      (0.025-0.25 mg/kg) administered before a 15-min exposure to forced swimming, and
      the response to a second session performed 24 h later, were examined. SCH 23390
      dose-dependently reduced climbing scores in the first session and increased them
      in the second session, but the within-session decline of this measure was similar
      to that observed in the control group in both sessions. Raclopride-treated
      subjects showed a slightly reduced level of climbing scores at the beginning of
      the first session, but persisted in emitting this costly behavioural response up
      to the end of the session, while no effects were observed in the second session.
      These results, along with our results examining licking for sucrose, are
      consistent with the hypothesis that behavioural activation and response effort
      allocation are directly mediated by dopamine D1-like receptor stimulation, but
      the level of this activation is updated, or "reboosted", on the basis of a
      dopamine D2-like receptor-mediated mechanism of response efficacy evaluation.

PMID- 22155446
TI  - A novel hydrogel electrolyte extender for rapid application of EEG sensors and
      extended recordings.
AB  - OBJECTIVE: Dense-array EEG recordings are now commonplace in research and gaining
      acceptance in clinical settings. Application of many sensors with traditional
      electrolytes is time consuming. Saline electrolytes can be used to minimize
      application time but recording duration is limited due to evaporation. In the
      present study, we evaluate a NIPAm (N-isopropyl acrylamide:acrylic acid) base
      electrolyte extender for use with saline electrolytes. METHODS: Sensor-scalp
      impedances and EEG data quality acquired with the electrolyte extender are
      compared with those obtained for saline and an EEG electrolyte commonly used in
      clinical exams (Elefix). RESULTS: The results show that when used in conjunction
      with saline, electrode-scalp impedances and data across the EEG spectrum are
      comparable with those obtained using Elefix EEG paste. CONCLUSIONS: When used in
      conjunction with saline, the electrolyte extender permits rapid application of
      dense-sensor arrays and stable, high-quality EEG data to be obtained for at least
      4.5 h. SIGNIFICANCE: This is an enabling technology that will make benefits of
      dense-array EEG recordings practical for clinical applications.

PMID- 22155447
TI  - Isolation of Robinsoniella peoriensis from the feces of premature neonates.
AB  - Robinsoniella peoriensis is a recently described anaerobic, spore-forming, Gram
      positive bacillus originally recovered from swine-manure and clinical human
      samples. In this study, R. peoriensis was isolated from the feces of one set of
      twin premature neonates. It suggests that this anaerobic bacillus may be a
      commensal bacterium of human gut.

PMID- 22155448
TI  - Comparison of different video laryngoscopes for emergency intubation in a
      standardized airway manikin with immobilized cervical spine by experienced
      anaesthetists. A randomized, controlled crossover trial.
AB  - BACKGROUND: The aim of the present study was to evaluate whether different video
      laryngoscopes (VLs) facilitate endotracheal intubation (ETI) faster or more
      secure than conventional laryngoscopy in a manikin with immobilized cervical
      spine. METHODS: After local ethics board approval, a standard airway manikin with
      cervical spine immobilization by means of a standard stiff collar was placed on a
      trauma stretcher. We compared times until glottic view, ETI, cuff block and first
      ventilation were achieved, and verified the endotracheal tube position, when
      using Macintosh laryngoscope, Glidescope Ranger, Storz C-MAC, Ambu Pentax AWS,
      Airtraq, and McGrath Series5 VLs in randomized order. Wilcoxon signed-rank test
      and McNemar's test were used for statistical analysis; p<0.05 was considered as
      significant. RESULTS: Twenty-three anaesthetists (mean age 32.1+/-4.9 years, mean
      experience in anaesthesia of 6.9+/-4.8 years) routinely involved in the
      management of multitrauma patients participated. The primary study end point,
      time to first effective ventilation, was achieved fastest when using Macintosh
      laryngoscope (21.0+/-7.6s) and was significantly slower with all other devices
      (Airtraq 33.2+/-23.9 s, p=0.002; Pentax AirwayScope 32.4+/-14.9 s, p=0.001; Storz
      C-MAC 34.1+/-23.9 s, p<0.001; McGrath Series5 101.7+/-108.3 s, p<0.001;
      Glidescope Ranger 46.3+/-59.1 s, p=0.001). Overall success rates were highest
      when using Macintosh, Airtraq and Storz C-MAC devices (100%), and were lower in
      Ambu Pentax AWS and Glidescope Ranger (87%, p=0.5) and in McGrath Series5 device
      (72.2%, p=0.063). CONCLUSION: When used by experienced anaesthesiologists, video
      laryngoscopes did not facilitate endotracheal intubation in this model with an
      immobilized cervical spine in a faster or more secure way than conventional
      laryngoscopy. However, data was gathered in a standardized model and further
      studies in real trauma patients are desirable to verify our findings.

PMID- 22155449
TI  - Out-of-hospital extracorporeal life support--when is it appropriate?

PMID- 22155450
TI  - Galectin-1 and galectin-3 expression profiles in classically and alternatively
      activated human macrophages.
AB  - BACKGROUND: Galectins have been identified as modulators of many
      monocyte/macrophage functions. In the response to a wide range of environmental
      cues macrophages may exhibit different biochemical and biological
      characteristics, but two main subtypes, classically (M1) and alternatively (M2)
      activated macrophages have been recognized. To contribute to elucidation of role
      and regulation of galectin-1 and galectin-3 in differently activated macrophages
      we explored their expression profiles in these cells. METHODS: Human monocytes
      obtained from blood donors were differentiated into classically (M1) and
      alternatively (M2a/M2c) activated macrophages. Gene and protein expression levels
      of intra- and extracellular galectins were investigated by qRT-PCR, Western-blot,
      flow cytometry, and ELISA while cytokine and surface receptor expression
      profiling was performed by flow cytometry. RESULTS: Differentiation/polarization
      of human monocytes into classically (M1) and alternatively (M2a/M2c) activated
      macrophages was followed by profound changes of galectin-3 expression and its
      proteolytic cleavage. Expression and secretion of Gal-3 was tightly regulated and
      significantly differed among classically (M1) and alternatively (M2a/M2c)
      activated macrophages, while the differences of galectin-1 expression profiles
      were not as pronounced. Human monocytes exhibited high amount of free galectin-3
      receptors, while on both types of activated macrophages were fully saturated.
      CONCLUSIONS: Galectin-3 is more distinctive descriptor of macrophages
      differentiation/activation than galectin-1. Its specific expression and secretion
      pattern in M1 vs. M2a/M2c macrophages contributes to better understanding of its
      role and regulation in these cells. GENERAL SIGNIFICANCE: Recognition of distinct
      galectin-1 and galectin-3 expression profiles in differently activated
      macrophages provides a new insight on biological characteristics of these cells
      and sheds a new light of galectin-3 as a modulator of individual macrophage
      subset. This article is part of a Special Issue entitled Glycoproteomics.

PMID- 22155451
TI  - The proteoglycan syndecan 4 regulates transient receptor potential canonical 6
      channels via RhoA/Rho-associated protein kinase signaling.
AB  - OBJECTIVE: Syndecan 4 (Sdc4) modulates signal transduction and regulates activity
      of protein channels. Sdc4 is essential for the regulation of cellular
      permeability. We hypothesized that Sdc4 may regulate transient receptor potential
      canonical 6 (TRPC6) channels, a determinant of glomerular permeability, in a
      RhoA/Rho-associated protein kinase-dependent manner. METHODS AND RESULTS: Sdc4
      knockout (Sdc4(-/-)) mice showed increased glomerular filtration rate and
      ameliorated albuminuria under baseline conditions and after bovine serum albumin
      overload (each P<0.05). Using reverse transcription-polymerase chain reaction and
      immunoblotting, Sdc4(-/-) mice showed reduced TRPC6 mRNA by 79% and TRPC6 protein
      by 82% (each P<0.05). Sdc4(-/-) mice showed an increased RhoA activity by 87% and
      increased phosphorylation of ezrin in glomeruli by 48% (each P<0.05). Sdc4
      knockdown in cultured podocytes reduced TRPC6 gene expression and reduced the
      association of TRPC6 with plasma membrane and TRPC6-mediated calcium influx and
      currents. Sdc4 knockdown inactivated negative regulatory protein Rho GTPase
      activating protein by 33%, accompanied by a 41% increase in RhoA activity and
      increased phosphorylation of ezrin (P<0.05). Conversely, overexpression of Sdc4
      reduced RhoA activity and increased TRPC6 protein and TRPC6-mediated calcium
      influx and currents. CONCLUSIONS: Our results establish a previously unknown
      function of Sdc4 for regulation of TRPC6 channels and support the role of Sdc4
      for the regulation of glomerular permeability.

PMID- 22155452
TI  - Apolipoprotein B secretion is regulated by hepatic triglyceride, and not insulin,
      in a model of increased hepatic insulin signaling.
AB  - OBJECTIVE: States of insulin resistance, hyperinsulinemia, and hepatic steatosis
      are associated with increased secretion of triglycerides (TG) and apolipoprotein
      B (apoB), even though insulin targets apoB for degradation. We used hepatic
      specific "phosphatase and tensin homologue deleted on chromosome 10" (Pten)
      knockout (hPten-ko) mice, with increased hepatic insulin signaling, to determine
      the relative roles of insulin signaling and hepatic TG in regulating apoB
      secretion. METHODS AND RESULTS: TG and apoB secretion was elevated in hPten-ko
      mice. When hepatic TG was reduced by inhibition of diacylglycerol acyltransferase
      1/diacylglycerol acyltransferase 2 or sterol regulatory element-binding protein
      1c, both TG secretion and apoB secretion fell without changes in hepatic insulin
      signaling. Acute reconstitution of hPten reduced hepatic TG content, and both TG
      and apoB secretion fell within 4 days despite decreased hepatic insulin
      signaling. Acute depletion of hepatic Pten by adenoviral introduction of Cre into
      Pten floxed mice caused steatosis within 4 days, and secretion of both TG and
      apoB increased despite increased hepatic insulin signaling. Even when steatosis
      after acute Pten depletion was prevented by pretreatment with SREBP-1c antisense
      oligonucleotides, apoB secretion was not reduced after 4 days. Ex vivo results
      were in primary hepatocytes were similar. CONCLUSIONS: Either hepatic TG is the
      dominant regulator of apoB secretion or any inhibitory effects of hepatic insulin
      signaling on apoB secretion is very short-lived.

PMID- 22155453
TI  - Platelet glycoprotein VI dimerization, an active process inducing receptor
      competence, is an indicator of platelet reactivity.
AB  - OBJECTIVE: The immune receptor homologue glycoprotein VI (GPVI)/FcR receptor
      gamma chain complex is primarily responsible for platelet activation by collagen.
      There is growing evidence that optimal binding of GPVI to collagen depends on the
      assembly of GPVI dimers. The valence of GPVI on resting platelets needs to be
      clearly established because platelet avidity for collagen would be greater if
      GPVI is constitutively expressed as a dimer than as a monomer. METHODS AND
      RESULTS: Using a monoclonal antibody (9E18) that preferentially binds to GPVI
      dimers, we found that GPVI was maintained in a monomeric form on human resting
      platelets under the control of intraplatelet cAMP concentration. Activation by
      soluble agonists or von Willebrand factor induced a shift toward GPVI
      dimerization related to increased platelet adhesion to collagen. A correlation
      between platelet binding of 9E18 and P-selectin exposure was observed in patients
      experiencing coronary artery disease, and antagonists of the ADP receptor P2Y12
      limited ADP-induced GPVI dimerization. CONCLUSION: The rapid assembly of highly
      competent dimers of GPVI at sites of vascular lesion represents an important step
      in the sequence of events leading to platelet activation by collagen. GPVI dimers
      could represent a new marker to analyze platelet reactivity.

PMID- 22155454
TI  - Resolution of mitochondrial oxidative stress rescues coronary collateral growth
      in Zucker obese fatty rats.
AB  - OBJECTIVE: We have previously found abrogated ischemia-induced coronary
      collateral growth in Zucker obese fatty (ZOF) rats compared with Zucker lean
      (ZLN) rats. Because ZOF rats have structural abnormalities in their mitochondria
      suggesting dysfunction and also show increased production of O(2), we
      hypothesized that mitochondrial dysfunction caused by oxidative stress impairs
      coronary collateral growth in ZOF. METHODS AND RESULTS: Increased levels of
      reactive oxygen species were observed in aortic endothelium and smooth muscle
      cells in ZOF rats compared with ZLN rats. Reactive oxygen species levels were
      decreased by the mitochondria-targeted antioxidants MitoQuinone (MQ) and
      MitoTempol (MT) as assessed by MitoSox Red and dihydroethidine staining. Lipid
      peroxides (a marker of oxidized lipids) were increased in ZOF by ~47% compared
      with ZLN rats. The elevation in oxidative stress was accompanied by increased
      antioxidant enzymes, except glutathione peroxidase-1, and by increased uncoupling
      protein-2 in ZOF versus ZLN rats. In addition, elevated respiration rates were
      also observed in the obese compared with lean rats. Administration of MQ
      significantly normalized the metabolic profiles and reduced lipid peroxides in
      ZOF rats to the same level observed in lean rats. The protective effect of MQ
      also suppressed the induction of uncoupling protein-2 in the obese rats.
      Resolution of mitochondrial oxidative stress by MQ or MT restored coronary
      collateral growth to the same magnitude observed in ZLN rats in response to
      repetitive ischemia. CONCLUSIONS: We conclude that mitochondrial oxidative stress
      and dysfunction play a key role in disrupting coronary collateral growth in
      obesity and the metabolic syndrome, and elimination of the mitochondrial
      oxidative stress with MQ or MT rescues collateral growth.

PMID- 22155456
TI  - Genetic variation in ABCG1 and risk of myocardial infarction and ischemic heart
      disease.
AB  - OBJECTIVE: ATP binding cassette transporter G1 (ABCG1) facilitates cholesterol
      efflux from macrophages to mature high-density lipoprotein particles. Whether
      genetic variation in ABCG1 affects risk of atherosclerosis in humans remains to
      be determined. METHODS AND RESULTS: We resequenced the core promoter and coding
      regions of ABCG1 in 380 individuals from the general population. Next, we
      genotyped 10 237 individuals from the Copenhagen City Heart Study for the
      identified variants and determined the effect on lipid and lipoprotein levels and
      on risk of myocardial infarction (MI) and ischemic heart disease (IHD). g.
      376C>T, g.-311T>A, and Ser630Leu predicted risk of MI in the Copenhagen City
      Heart Study, with hazard ratios of 2.2 (95% confidence interval: 1.2-4.3), 1.7
      (1.0-2.9), and 7.5 (1.9-30), respectively. These results were confirmed for g.
      376C>T in a case-control study comprising 4983 independently ascertained IHD
      cases and 7489 controls. Expression levels of ABCG1 mRNA were decreased by
      approximately 40% in g.-376C>T heterozygotes versus noncarriers (probability
      values: 0.005-0.009). Finally, in vitro specificity protein 1 (Sp1) bound
      specifically to a putative Sp1 binding site at position -382 to -373 in the ABCG1
      promoter, and the presence of the -376 T allele reduced binding and
      transactivation of the promoter by Sp1. CONCLUSIONS: This is the first report of
      a functional variant in ABCG1 that associates with increased risk of MI and IHD
      in the general population.

PMID- 22155455
TI  - Urokinase-type plasminogen activator downregulates paraoxonase 1 expression in
      hepatocytes by stimulating peroxisome proliferator-activated receptor-gamma
      nuclear export.
AB  - OBJECTIVE: The atherosclerotic lesion is characterized by lipid peroxide
      accumulation. Paraoxonase 1 (PON1) reduces atherosclerotic lesion oxidative
      stress, whereas urokinase-type plasminogen activator (uPA) increases oxidative
      stress in atherosclerotic lesions and contributes to the progression and
      complications of atherosclerosis. We hypothesized that uPA may promote oxidative
      stress in the arterial wall via modulation of PON1 activity. Because the liver is
      the main site for PON1 production, in the present study, we tested whether uPA
      influences PON1 expression in hepatocytes. METHODS AND RESULTS: HuH7 hepatocytes
      were incubated in culture with increasing concentrations of uPA. uPA decreased
      PON1 gene expression and activity in a dose-dependent manner and accordingly
      suppressed PON1 secretion from hepatocytes. This effect required uPA/uPA receptor
      interaction. uPA downregulated PON1 gene expression via inactivation of
      peroxisome proliferator-activated receptor-gamma (PPARgamma) activity, and this
      effect was dependent on uPA-mediated mitogen-activated protein kinase kinase
      activation. Mechanistic studies showed that uPA enhanced mitogen-activated
      protein kinase kinase-PPARgamma interaction, resulting in PPARgamma nuclear
      export to the cytosol. CONCLUSIONS: This study provides the first evidence that
      uPA interferes with PPARgamma transcriptional activity in hepatocytes, resulting
      in downregulation of PON1 expression and its secretion to the medium. This may
      explain, at least in part, the prooxidative effect of uPA in the vascular wall.

PMID- 22155457
TI  - Preventive effects of exenatide on endothelial dysfunction induced by ischemia
      reperfusion injury via KATP channels.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether exenatide
      administration can prevent impairment in endothelium-dependent vasodilatation
      induced by ischemia-reperfusion (IR) injury and whether this effect is mediated
      by K(ATP) channel opening. METHODS AND RESULTS: In a double-blind, placebo
      controlled, crossover design, 20 volunteers were randomly assigned to 2 groups:
      subcutaneous exenatide (10 MUg) or placebo administration. At 30 minutes after
      the study drug administration, endothelium-dependent flow-mediated dilatation
      (FMD) of the radial artery was measured before and after IR (15 minutes of
      ischemia at the level of the brachial artery followed by 15 minutes of
      reperfusion) injury. Seven days later, both groups were crossed over and received
      the other treatment (ie, placebo or exenatide) and underwent the same protocol.
      Pre-IR radial artery diameter, FMD, and baseline radial artery diameter after IR
      injury were similar between 2 groups (P=no significant difference). After placebo
      administration, IR significantly blunted FMD (before IR: 12.0+/-6.23%; after IR:
      4.6+/-3.57%, P=0.02). Exenatide prevented this impairment (FMD before IR: 15.0+/
      7.14%; FMD after IR: 15.0+/-5.96%, P=no significant difference; P<0.001 compared
      with placebo). In a separate protocol, this protective effect was completely
      abolished by pretreatment with glibenclamide (glyburide, 5 mg), a blocker of
      K(ATP) channels (n=7; FMD before IR: 12.0+/-2.2%; after IR: 3.2+/-2.1%, P<0.001).
      CONCLUSIONS: The present study demonstrates that subcutaneous exenatide protects
      IR-induced endothelial dysfunction through opening of K(ATP) channels in human IR
      injury model.

PMID- 22155458
TI  - A review of the principles of radiological assessment of skeletal dysplasias.
AB  - There are more than 450 well-characterized skeletal dysplasias classified
      primarily on the basis of clinical, radiographic, and molecular criteria. In the
      latest 2010 revision of the Nosology and Classification of Genetic Skeletal
      Disorders, an increase from 372 to 456 disorders had occurred in the four years
      since the classification was last revisited in 2007. These entities in total
      represent about 5% of children with birth defects. An accurate diagnosis of a
      skeletal dysplasia is still based on detailed evaluation of clinical and
      radiographic [as well as chondro-osseous] findings. Regardless of the specific
      diagnosis, skeletal dysplasias in general share clinical and radiological
      findings helping us to group them in several ways. This review aims to outline
      the diagnostic approach to disproportionate short stature with special emphasis
      on radiological findings.

PMID- 22155459
TI  - Vitamin D deficiency in children and adolescents with type 1 diabetes.
AB  - OBJECTIVE: To investigate the frequency and effects of vitamin D deficiency in
      children with type 1 diabetes (T1D) in a region which is known to have a high
      rate of vitamin D deficiency among adolescents. METHODS: In this prospective
      cross-sectional study, 120 children and adolescents with T1D (55 girls and 65
      boys) aged 3-20 years were evaluated. Serum 25-hydroxyvitamin D [25(OH)D],
      parathormone (PTH), and alkaline phosphatase (ALP) levels were measured.
      Hemoglobin A1c levels and daily insulin requirement were also evaluated.
      Classification of vitamin D status was made according to the American Academy of
      Pediatrics (AAP)/LWEPS's recommendations. The patients were divided into 2 groups
      according to their vitamin D status and also according to the season of the year
      in which 25(OH)D sampling was done. RESULTS: Serum 25(OH)D levels revealed
      vitamin D deficiency or insufficiency in 38% of the patients. Higher PTH levels
      were found in the patient group whose mean 25(OH)D level was < 20 ng/mL as
      compared to the group whose mean 25(OH)D level was > 20 ng/mL (p < 0.05). Only
      11% of patients had secondary hyperparathyroidism. The 25(OH)D levels of patients
      whose serum samples were taken in summer and spring months were significantly
      different (p < 0.05). There were no significant correlations between 25(OH)D
      level and daily insulin dose. CONCLUSION: Although we could not show a
      significant association between vitamin D deficiency and metabolic parameters,
      the frequency of vitamin D deficiency in T1D children is substantial. Vitamin D
      status should be assessed also in patients who do not have signs of rickets.

PMID- 22155460
TI  - Weight and height percentiles for 0-84- month-old children in Kayseri--a central
      Anatolian city in Turkey.
AB  - OBJECTIVE: The aim of this study was to present weight and height percentiles for
      Turkish children aged 0-84 months residing in Kayseri, Turkey and to compare
      these findings with national references and international standards. METHODS: We
      used the data from the Anthropometry of Turkish Children aged 0-6 years (ATCA-06)
      study. This cross-sectional study conducted in Kayseri/Turkey between September
      2009 and May 2010 included 2963 children (1491 girls, 1472 boys) aged 0-84
      months. The centile curves were constructed using the LMS method. RESULTS: The
      3rd, 5th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, 95th, and 97th percentiles
      and the LMS values for boys and girls were constructed. The 50th percentiles for
      weight and height of the children were compared with world health organization
      (WHO) standards and national data. Height and weight values in Kayseri children
      were lower than WHO standards and Istanbul references in the first year of life.
      At ages 1 to 4, weight values in both genders and height in boys were slightly
      higher than the national and international standards. Starting at age 4 years,
      the weight percentiles of Kayseri children were strikingly higher compared to the
      national and international standards and the boys were also taller. CONCLUSIONS:
      This study provides cross-sectional data for weight and height percentiles of
      Turkish children aged 0-84 months residing in Kayseri. These data reflect the
      growth status of healthy Kayseri children and also indicate that these children
      may be more prone to obesity than the Istanbul children. Since the above
      mentioned data illustrate the current growth status of this population, we
      believe that they will serve as a basis for monitoring future trends.

PMID- 22155461
TI  - Clinical course of Hashimoto's thyroiditis and effects of levothyroxine therapy
      on the clinical course of the disease in children and adolescents.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical course of
      Hashimoto's thyroiditis (HT) in children and adolescents and the effects of
      levothyroxine therapy on the clinical course and laboratory findings. METHODS:
      The clinical and laboratory data of 101 patients with HT at presentation and
      during a three-year follow-up period were retrospectively evaluated using patient
      records. RESULTS: The mean age of the patients at the time of diagnosis was 12.3
      +/- 2.90 years and female/male ratio was 5.7/1. The complaint at the time of
      hospital presentation was goiter in 57.8% of the patients. At baseline, 36.7% of
      the patients were euthyroid, whereas 32.7% had subclinical hypothyroidism, 16.6 %
      of subjects were evaluated as hypothyroid. Twelve of the 28 patients who were
      initially euthyroid and not receiving therapy developed subclinical or overt
      hypothyroidism during the first 18 months of the follow-up period and were
      started on thyroid medication. At presentation, the mean anti-thyroglobulin (anti
      Tg) and anti-thyroperoxidase antibody levels were 450 +/- 725 IU/mL and 392 +/-
      428 IU/mL, respectively and at the end of the follow-up period, a significant
      decrease was observed in the anti-Tg levels of patients receiving levothyroxine
      from the beginning. CONCLUSIONS: Thyroid functions of the patients with HT should
      be monitored periodically for hypothyroidism. Levothyroxine therapy may
      positively affect the clinical course of the disease and the antibody titers.

PMID- 22155462
TI  - No relationship between vitamin D status and insulin resistance in a group of
      high school students.
AB  - OBJECTIVE: To investigate the effects of vitamin D deficiency on both insulin
      resistance and risk of metabolic syndrome in children. METHODS: The study group
      consisted of 301 children and adolescents with a mean age of 14.2 +/- 1.8 years.
      Serum 25-hydroxyvitamin D [25(OH)D] levels and insulin resistance indices were
      evaluated. According to serum 25(OH)D levels, the subjects were classified in 3
      groups. Those with levels <= 10 ng/mL were labeled as the vitamin D deficient
      group (group A), those with levels of 10-20 ng/mL as the vitamin D insufficient
      group (group B) and those with >= 20 ng/mL as having normal vitamin D levels
      (group C). Metabolic syndrome was defined according to the International Diabetes
      Federation consensus. The participants with and without metabolic syndrome were
      compared in terms of 25(OH)D levels. RESULTS: Mean 25(OH)D level of the total
      group was 18.2 +/- 9.3 (2.8-72.0) ng/mL. Distribution of individuals according to
      their vitamin D levels showed that 11.6% were in group A, 53.5% in group B, and
      34.9% in group C. The proportions of boys and girls in these categories were
      22.9% and 77.1% in group A, 36.6% and 63.4% in group B, 54.3% and 45.7% in group
      C, respectively. There were no significant differences in 25(OH)D levels in the
      individuals with and without impaired fasting glucose or impaired glucose
      tolerance. No relationship was observed between insulin resistance/sensitivity
      indices and vitamin D status (p > 0.05). Metabolic syndrome was diagnosed in
      12.3% (n = 37) of the children. There was also no difference in mean 25(OH)D
      levels between individuals who had and those who did not have the metabolic
      syndrome. CONCLUSION: In our study, no correlations were found between insulin
      measurements during oral glucose tolerance test and vitamin D deficiency.
      Nonetheless, more extended studies including vitamin D supplementation and
      evaluating insulin sensitivity via clamp technique are needed to further
      elucidate this relationship.

PMID- 22155463
TI  - Metabolic control in children and adolescents with insulin-dependent diabetes
      mellitus at King Abdul-Aziz University Hospital.
AB  - OBJECTIVE: Preventing long-term diabetic complications requires good metabolic
      control, especially in type 1 diabetes mellitus (T1DM). We describe the metabolic
      control of T1DM and the factors affecting it among children and adolescents
      attending the Pediatric Clinic at King Abdul-Aziz University Hospital. METHODS: A
      retrospective cross-sectional study was conducted on T1DM children and
      adolescents who had attended the Pediatric Clinic at King Abdul-Aziz University
      Hospital from 2006 to 2010. Both clinical and laboratory data were reviewed for
      the enrolled cases. The mean age of the patients was 12.5 +/- 4.1 years. Ages
      ranged from 1 to 18 years (n = 484: male = 213, female = 271). 38.6% of the
      patients were pre-pubertal and 61.4%-- pubertal. The patients were categorized
      into 3 age groups as 1-6 years (10.3%), 7-12 years (33.5%) and 13-18 years
      (56.2%). RESULTS: The overall mean HbA1c was 9.4 +/- 2.4% and the duration of
      patient follow-up was 26 +/- 17 months. 10.3% of the patients were on
      conventional insulin regimens and 89.7%--on intensive insulin therapy. 31.4% had
      satisfactory HbA1c according to the American Diabetes Association guidelines. The
      duration of T1DM was 2.9 +/- 1.4 years. The patients with diabetes duration <= 2
      years (45%) had a mean HbA1c of 8.7 +/- 1.8% and those with diabetes duration > 2
      years (55%) had a mean HbA1c value of 9.8 +/- 2.3% (p < 0.001). CONCLUSIONS: The
      metabolic control of T1DM children in our cohort was less satisfactory than in
      other studies. We recommend the promotion of physical exercise and family
      educational programs to improve the metabolic control of T1DM pediatric patients
      in our population.

PMID- 22155464
TI  - Congenital hypothyroidism with neurological and respiratory alterations: a case
      detected using a variable diagnostic threshold for TSH.
AB  - We report a case of congenital hypothyroidism (CH) with neurological and
      respiratory alterations due to a heterozygotic c.374-1G > A mutation of
      TITF1/NKX2-1. The hypothyroidism was detected using a neonatal screening protocol
      in which the thyroid stimulating hormone (TSH) threshold is re-set each day on
      the basis of within-day variability and between-day variation. In this case, the
      threshold on the day of the initial analysis was 8.2 mIU/L, and the measured TSH
      level in heel-prick blood was 8.3 mIU/L.

PMID- 22155465
TI  - Resolution of autoimmune oophoritis after thymectomy in a myasthenia gravis
      patient.
AB  - Myasthenia gravis (MG) is an autoimmune disorder characterized by autoantibodies
      against acetylcholine receptors. MG is generally an isolated disorder but may
      occur concomitantly with other autoimmune diseases. We describe an eighteen-year
      old girl with MG who was admitted to our clinic with secondary amenorrhea and
      diagnosed as autoimmune oophoritis. Since her myasthenic symptoms did not resolve
      with anticholinesterase therapy, thymectomy was performed. After thymectomy, her
      menses have been regular without any hormonal replacement therapy. To our
      knowledge, this is the first report on a patient with autoimmune ovarian
      insufficiency and MG in whom premature ovarian insufficiency resolved after
      thymectomy, without hormonal therapy.

PMID- 22155466
TI  - Follow-up during early infancy of newborns diagnosed with subcutaneous fat
      necrosis.
AB  - Subcutaneous fat necrosis of the newborn (ScFN) is an uncommon condition caused
      by generalized and/or local tissue hypoperfusion. The skin lesions of ScFN tend
      to improve spontaneously. However, ScFN may also lead to complications which
      cause serious problems. The severity of the etiologic factors contributing to the
      development of the disease determines the severity of complications. Therefore,
      these patients should be closely monitored for complications, especially for
      hypercalcemia which may be life-threatening. The severity and duration of
      hypercalcemia are associated with the extensity of skin lesions. We present a
      newborn who developed ScFN as a result of systemic hypotension. The ScFN resolved
      after the first few weeks of life, but the patient developed mild hypercalcemia
      during the 4-month follow-up period. The infant was breast-fed during follow-up,
      and vitamin D prophylaxis was not initiated. The hypercalcemia resolved within
      four months without any complications. We would like to draw attention to the
      need to monitor serum calcium levels in these infants and to refrain from
      initiating vitamin D prophylaxis in the first months of life.

PMID- 22155467
TI  - Does pseudohypoaldosteronism mask the diagnosis of congenital adrenal
      hyperplasia?
AB  - Hyponatremia and hyperpotassemia occurring in the first few weeks of life
      primarily indicate aldosterone deficiency due to salt-losing congenital adrenal
      hyperplasia (SL-CAH), while mineralocorticoid deficiency and insensitivity are
      the main causes of hyponatremia and hyperpotassemia in older infants. Some
      patients who present with vomiting and poor sucking, who have hyponatremia and
      hyperpotassemia and are initially diagnosed as CAH, during follow-up, are found
      to suffer from pseudohypoaldosteronism (PHA). This situation has been reported
      several times before. The cases described here represent the opposite situation:
      they presented with hyponatremia and hyperpotassemia, thus PHA was considered as
      aldosterone levels were very high, but subsequent investigation and genetic
      analysis led to the diagnosis of SL-CAH.

PMID- 22155468
TI  - Tuberculous meningitis associated with diabetic ketoacidosis.
AB  - Diabetic ketoacidosis (DKA) is a life-threatening acute complication of type 1
      diabetes mellitus. Infections are the leading cause of DKA, but trauma,
      myocardial infarction, or surgery may also precipitate this condition. In
      patients with DKA, although cerebral edema is the most common cause of
      neurological symptoms, other possibilities such as meningitis or encephalitis
      should also be considered. Herein, we present the case of an 8-year-old girl with
      DKA and tuberculous meningitis.

PMID- 22155469
TI  - Investigation of local primary structure effects on peroxynitrite-mediated
      tyrosine nitration using targeted mass spectrometry.
AB  - Protein-tyrosine nitration (PTN) is a posttranslational modification resulting
      from cellular nitrosative stress that has been implicated in a wide variety of
      disease states. Determination of factors that influence selectivity of PTN
      remains a major challenge due to several issues including low biological levels
      of PTN, proximity of target sites on a single analyte, and analytical limitations
      for site-specific quantification of the nitration modification. We report a
      systematic approach that addresses relevant contributing factors to PTN with
      particular focus on determining the effect of changing proximal amino acid side
      chain structure on tyrosine nitration yield. A trend was observed in which
      nitration yield tends to be greater when the tyrosine residue is surrounded by
      basic and/or uncharged polar residues compared to nitration levels observed when
      hydrophobic and acidic residues are proximal to the tyrosine residue. Moreover,
      an electric dipole effect was observed where a higher degree of charge asymmetry
      surrounding the tyrosine residue correlates with an increased tyrosine nitration
      yield in certain cases. The reported data are expected to facilitate site
      specific prediction and validation of PTN, especially in cases of potential
      target residues that share a similar solvent exposure environment and contain
      elements of known higher-order structure.

PMID- 22155470
TI  - Comparative proteomic analysis of seedling leaves of different salt tolerant
      soybean genotypes.
AB  - Salinity is one of the major environmental constraints limiting yield of crop
      plants in many semi-arid and arid regions around the world. To understand
      responses in soybean seedling to salt stress at proteomic level, the extracted
      proteins from seedling leaves of salt-sensitive genotype Jackson and salt
      tolerant genotype Lee 68 under 150 mM NaCl stress for 1, 12, 72 and 144 h,
      respectively, were analyzed by 2-DE. Approximately 800 protein spots were
      detected on 2-DE gels. Among them, 91 were found to be differently expressed,
      with 78 being successfully identified by MALDI-TOF-TOF. The identified proteins
      were involved in 14 metabolic pathways and cellular processes. Based on most of
      the 78 salt-responsive proteins, a salt stress-responsive protein network was
      proposed. This network consisted of several functional components, including
      balancing between ROS production and scavenging, accelerated proteolysis and
      reduced biosynthesis of proteins, impaired photosynthesis, abundant energy supply
      and enhanced biosynthesis of ethylene. Salt-tolerant genotype Lee 68 possessed
      the ability of higher ROS scavenging, more abundant energy supply and ethylene
      production, and stronger photosynthesis than salt-sensitive genotype Jackson
      under salt stress, which may be the major reasons why it is more salt-tolerant
      than Jackson.

PMID- 22155471
TI  - Knowledge of ethnoveterinary medicine in the Province of Granada, Andalusia,
      Spain.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper constitutes an important contribution
      to the knowledge of biological resources used in ethnoveterinary practices (EVPs)
      in southern Europe, a territory with a clear lack of information on the subject.
      AIM OF THE STUDY: To catalogue, analyze, and disseminate the knowledge of plant
      and animal use in ethnoveterinary practices in the province of Granada. Data have
      been analyzed to highlight the similarities between ethnoveterinary practices and
      human ethnopharmacology for the same study area. METHODOLOGY: Information was
      gathered through open and semi-structured interviews with local people, mainly
      elderly shepherds and farmers, in the western part of the province. The primary
      data have been supplemented with information on EVPs from previous ethnobotanical
      works for the province. Data were gathered using the same field methods. RESULTS:
      A total of 88 ethnoveterinary uses are documented for the treatment of 24 animal
      conditions. Of these, 82 uses involve 60 different plant species. Over three
      quarters of these plants are also used for some human conditions in the same
      study area. Moreover, 6 animal species were catalogued for 6 other
      ethnoveterinary uses; four of these species were also used for similar conditions
      in humans. Ritual and health-prevention practices are also discussed.
      CONCLUSIONS: EVPs in southern Spain involve a high number of species and
      conditions and are strongly linked to folk tradition (i.e. how local people
      understand certain conditions and their treatment, sometimes in a ritual manner).
      Unfortunately, some evidence of their slow disappearance has been found.

PMID- 22155472
TI  - Effect of Opuntia streptacantha Lem. on alpha-glucosidase activity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In Mexico, Opuntia streptacantha is used as part
      of a traditional medicine in the treatment of diabetes mellitus. Several studies
      have reported an anti-hyperglycemic effect from the plant, but none have focused
      on finding a mechanism of action to explain these results. This paper focuses on
      one of the most recurrent hypotheses for the effect of O. streptacantha: the
      mechanism of action is the hydrolysis of disaccharides, either by enzymatically
      inhibiting the alpha glucosidase inhibitors (AGIs) or mechanically acting as a
      barrier. MATERIALS AND METHODS: To test our hypothesis, three different
      experiments were performed. A maltose tolerance test was carried out using the
      total extract (TE) and the juice of the plant. Six different extracts were tested
      in a free-enzyme assay, four of which were aqueous extracts varying according to
      the procedure of removing the insoluble particles in an attempt to reduce the
      loss of the water-soluble compounds. The main component of the total extract, a
      derivative of (4-hydroxy)-phenyl acetic acid, was also tested. For both the
      maltose tolerance test and the free-enzyme assay, acarbose was used as a control
      drug. Finally, an everted small intestine assay was also performed. RESULTS AND
      CONCLUSIONS: The maltose tolerance test confirmed that an anti-hyperglycemic
      effect occurs at doses of 100 mg/kg TE and 4 mL/kg juice. No inhibition on AGIs
      was observed in the free-enzyme assay, and neither a mechanic nor enzymatic
      effect on disaccharide hydrolysis was observed in the everted intestine assay.
      CONCLUSIONS: The anti-hyperglycemic effect of O. streptacantha was confirmed, and
      the results presented here contribute to the understanding that this effect is
      not due to the action on alpha-glucosidases or related to the intestinal
      hydrolysis of disaccharides.

PMID- 22155473
TI  - Relaxant effects of Artemisia ludoviciana on isolated rat smooth muscle tissues.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ludoviciana spp. mexicana (Willd. Ex.)
      Spring D.D. Keck (Asteraceae), known as "estafiate" is employed for the treatment
      of diarrhea, dysentery, parasites, abdominal pain, vomiting, stomach ache, and
      also as antispasmodic agent. The aim of the present study was to evaluate the
      relaxant effect of hexanic (HEAl), dichloromethanic (DEAl) and methanolic (MEAl)
      extracts on isolated trachea, ileum and aorta rat rings, and to establish the
      tracheo-relaxant mode of action of DEAl. MATERIALS AND METHODS: All extracts were
      investigated based on their capacity of to inhibit the rat ileum spontaneous
      contraction, to relax contraction induced by noradrenaline (0.1 MUM) on
      endothelium-intact and endothelium-denuded thoracic aorta rat rings, and also to
      inhibit contraction provoked by carbachol (1 MUM) on rat trachea. RESULTS:
      Organic extracts had no spasmolytic action on ileum strips compared to positive
      control (papaverine, p<0.05). On the other hand, all extracts induced a
      significant concentration- and partial endothelium-dependent vasorelaxant
      activity. Extracts also showed significant relaxant effect on pre-contracted
      tracheal tissue in a concentration-dependent manner. In last two experiments,
      DEAl was the most potent and efficient extract; however, it was less potent than
      papaverine and theophylline, used as positive controls (p<0.05). In tracheal
      preparation, DEAl shifted to the right, in a parallel manner, the concentration
      response curves induced by carbachol (p<0.05). Also, DEAl induced a significant
      relaxant effect on the contraction produced by potassium chloride (KCl, 80 mM).
      Pre-incubation with 1-H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one (ODQ, 10 MUM),
      indomethacin (10 MUM), N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 MUM),
      glibenclamide (10 MUM) and 2-aminopyridine (2-AP, 100 MUM) did not modify the
      DEAl-relaxant curves. CONCLUSIONS: Functional experiments suggest that the most
      active extract, DEAl, induced its relaxant effect by possible muscarinic
      receptors antagonism and calcium channel blockade in tracheal rings. On the other
      hand, significant vasorelaxant activity showed by DEAl is partially endothelium
      dependent. Finally, spasmolytic activity induced by the extracts in the rat ileum
      was not significant, which suggests that the antidiarrheic effect of the plant is
      related to antimicrobial and antiparasitic properties previously described.

PMID- 22155474
TI  - Delayed reactive cries demonstrate emotional and physiological dysregulation in
      newborns of depressed mothers.
AB  - The purpose of the present study was to examine newborns' behavioral and
      physiological reactions to the cry of another infant (labeled a reactive cry).
      101 newborns of depressed (N=40) and non-depressed (N=61) mothers were assessed
      on the Brazelton Neonatal Behavioral Assessment Scale (NBAS, Brazelton and
      Nugent, 1995) and 89 of those infants also participated in an auditory task.
      Cardiovascular activity (heart period, parasympathetic tone, and recovery to
      basal activity) was obtained from a sub-sample of these infants (n=37). Vocal
      distress and regulatory behaviors were examined when newborns listened to another
      infant's cry and to a simulated sound (the control condition). ANOVAs indicated
      that newborns of depressed mothers showed lower basal parasympathetic tone. In
      addition, newborns of depressed mothers responded with less vocal distress to the
      cry sounds of another infant, and were delayed in physiological regulation
      following this sound. These findings suggest that newborns of depressed mothers
      show altered, possibly dysregulated, behavioral and physiological patterns during
      socio-emotional situations in comparison to newborns of non-depressed mothers.

PMID- 22155475
TI  - Inadequate inhibition of redundant auditory inputs in Alzheimer's disease: an MEG
      study.
AB  - This study aimed to characterize the cortical deficits in processing auditory
      inputs in patients with Alzheimer's disease (AD). The magnetic counterparts of
      P50 (M50) and mismatch negativity (MMNm) during a passive oddball paradigm were
      analyzed with equivalent current dipole modeling. The results showed larger
      cortical activation of standard-evoked M50 in AD patients compared to young and
      elderly controls. In contrast, smaller amplitudes and longer peak latencies were
      found in the MMNm of the elderly and AD patients compared with young adults. The
      MMNm latency was longer in AD patients than in elderly controls. A Spearman
      correlation test showed an inverse correlation between the cortical strengths of
      M50 and MMNm in the right hemisphere. In conclusion, age-related changes in the
      M50 and MMNm components, which may reflect deficits in central auditory
      processing, are discussed, along with the possibility that increased M50
      responses are related to decreased inhibition of redundant inputs in mild AD.

PMID- 22155476
TI  - Neurokinin-1 receptor deletion modulates behavioural and neurochemical
      alterations in an animal model of depression.
AB  - The substance P/NK1 receptor system plays an important role in the regulation of
      stress and emotional responding and as such had been implicated in the
      pathophysiology of anxiety and depression. The present study investigated whether
      alterations in the substance P/NK1 receptor system in brain areas which regulate
      emotional responding accompany the depressive behavioural phenotype observed in
      the olfactory bulbectomised (OB) mouse. The effect of NK1 receptor deletion on
      behavioural responding and monoamine levels in discrete brain regions of the OB
      model, were also examined. Substance P levels in the frontal cortex and NK1
      receptor expression in the amygdala and hippocampus were enhanced following
      olfactory bulbectomy. Although NK1 receptor knockout (NK1-/-) mice did not
      exhibit altered behavioural responding in the open field test, noradrenaline
      levels were enhanced in the frontal cortex, amygdala and hippocampus, as were
      serotonin levels in the frontal cortex. Locomotor activity and exploratory
      behaviour were enhanced in wild type OB mice, indicative of a depressive-like
      phenotype, an effect attenuated in NK1-/- mice. Bulbectomy induced a decrease in
      noradrenaline and 5-HIAA in the frontal cortex and an increase in serotonin in
      the amygdala, effects attenuated in OB NK1-/- mice. The present studies indicate
      that alterations in substance P/NK1 receptor system underlie, at least in part,
      the behavioural and monoaminergic changes in this animal model of depression.

PMID- 22155477
TI  - Dopaminergic modulation of the updating of stimulus-response episodes in
      Parkinson's disease.
AB  - Increasing evidence suggests that the control of retrieval of episodic feature
      bindings is modulated by the striatal dopaminergic pathway. The present study
      investigated whether this may reflect a contribution from the ventral or the
      dorsal part of the striatum. Along the lines of the overdose hypothesis in
      Parkinson's disease (PD), functions known to rely on the dorsal striatum are
      enhanced with dopaminergic medication, while operations relying on the ventral
      circuitry are impaired. We found that partial mismatches between present and
      previous stimulus-response relations are, compared to control participants,
      abnormally low OFF DA medication and normalized ON DA medication. The results
      suggest that the dorsal striatum, but not (or not so much) the ventral striatum,
      is driving the flexible control of retrieval of stimulus-response episodes.

PMID- 22155478
TI  - The role of medial prefrontal cortex in theory of mind: a deep rTMS study.
AB  - Neuroimaging studies suggest that the medial prefrontal cortex (mPFC) plays a
      central role in cognitive theory of mind (ToM). This can be assessed more
      definitively, however, using repetitive transcranial magnetic stimulation (rTMS).
      Sixteen healthy participants (10 females, 6 males) completed tasks assessing
      cognitive and affective ToM following low-frequency deep rTMS to bilateral mPFC
      in active-stimulation and placebo-stimulation sessions. There was no effect of
      deep rTMS on either cognitive or affective ToM performance. When examining self
      reported empathy, however, there was evidence for a double dissociation: deep
      rTMS disrupted affective ToM performance for those with high self-reported
      empathy, but improved affective ToM performance for those with low self-reported
      empathy. mPFC appears to play a role in affective ToM processing, but the present
      study suggest that stimulation outcomes are dependent on baseline empathic
      abilities.

PMID- 22155479
TI  - Incident obesity and cardiovascular risk factors between young adulthood and
      middle age by religious involvement: the Coronary Artery Risk Development in
      Young Adults (CARDIA) study.
AB  - BACKGROUND: Religious involvement has been associated with improved health
      outcomes but greater obesity in older adults. No longitudinal study of young
      adults has examined the prospective association of religious involvement with
      incident cardiovascular risk factors (RFs) and subclinical disease (subCVD).
      METHODS: We included 2433 participants of the CARDIA study, aged 20 to 32 in 1987
      when religiosity was assessed, who were followed for 18 years. Multivariable
      adjusted regression models were fitted to assess prospective associations of
      frequency of religious participation at baseline with incidence of RFs and
      prevalence of subCVD after 18 years' follow up. RESULTS: The high frequency of
      religious participation was associated with a significantly greater incidence of
      obesity in unadjusted models (RR 1.57, 95% CI 1.14-1.73) and demographic-adjusted
      models (RR 1.34, 95% CI 1.09-1.65) but not after additional adjustment for
      baseline RFs (RR 1.17, 95% CI .97-1.41). When religious participation was treated
      dichotomously, any religious participation, compared with none, was associated
      with significantly lower subCVD. CONCLUSIONS: Frequent religious participants are
      more likely to become obese between young adulthood and middle age; this
      association is confounded by demographic and other factors. Nonetheless, young
      adults with frequent participation may represent an opportunity for obesity
      prevention.

PMID- 22155480
TI  - Trehalose transporter from African chironomid larvae improves desiccation
      tolerance of Chinese hamster ovary cells.
AB  - Dry preservation has been explored as an energy-efficient alternative to
      cryopreservation, but the high sensitivity of mammalian cells to desiccation
      stress has been one of the major hurdles in storing cells in the desiccated
      state. An important strategy to reduce desiccation sensitivity involves use of
      the disaccharide trehalose. Trehalose is known to improve desiccation tolerance
      in mammalian cells when present on both sides of the cell membrane. Because
      trehalose is membrane impermeant the development of desiccation strategies
      involving this promising sugar is hindered. We explored the potential of using a
      high-capacity trehalose transporter (TRET1) from the African chironomid
      Polypedilum vanderplanki[21] to introduce trehalose into the cytoplasm of
      mammalian cells and thereby increase desiccation tolerance. When Chinese hamster
      ovary cells (CHO) were stably transfected with TRET1 (CHO-TRET1 cells) and
      incubated with 0.4M trehalose for 4h at 37 degrees C, a sevenfold increase in
      trehalose uptake was observed compared to the wild-type CHO cells. Following
      trehalose loading, desiccation tolerance was investigated by evaporative drying
      of cells at 14% relative humidity. After desiccation to 2.60g of water per gram
      dry weight, a 170% increase in viability and a 400% increase in growth (after
      7days) was observed for CHO-TRET1 relative to control CHO cells. Our results
      demonstrate the beneficial effect of intracellular trehalose for imparting
      tolerance to partial desiccation.

PMID- 22155481
TI  - Dissecting DBS Dynamics through quantitative behavioral assessments and
      statistical modeling: a commentary on Cooper et al. 2011.

PMID- 22155482
TI  - Chemokines influence the migration and fate of neural precursor cells from the
      young adult and middle-aged rat subventricular zone.
AB  - We have previously demonstrated a role for the chemokines MCP-1, MIP-1alpha and
      GRO-alpha in directing subventricular zone (SVZ)-derived neural precursor cell
      migration towards the site of cell death in the adult rodent brain. However the
      influence of chemokines such as MCP-1, MIP-1alpha and GRO-alpha on the
      differentiation of adult neural precursor cells has not previously been
      investigated. Further, as the majority of neurological disorders and injuries
      occur during ageing, it is important to investigate the effect of chemokines on
      adult neural precursor cell cultures obtained from the ageing brain. This study
      therefore examined the effect of MCP-1, MIP-1alpha and GRO-alpha on SVZ-derived
      neural precursor cell differentiation in vitro, and assessed whether precursor
      cells from the middle-aged rat brain (13 months old) follow the same migratory
      and differential profile as neural precursor cells obtained from the young adult
      rat brain (2 months old). We observed that each of the chemokines examined
      generated differing effects in regards to neuronal or glial differentiation.
      Further, both MIP-1alpha and GRO-alpha increased total cell number, suggesting an
      effect on precursor cell proliferation and/or survival. In agreement with
      cultures obtained from young adult brains, SVZ-derived neural precursor cells
      cultured from the middle-aged brain exhibited chemotactic migration in response
      to a concentration gradient. These results indicate that the chemokines MCP-1,
      MIP-1alpha and GRO-alpha can influence both the migration and fate choice of SVZ
      derived neural precursor cells, as well as promoting cell viability. While a
      response to each of these chemokines is maintained in the middle-aged brain, a
      distinct age-related alteration in differential fate can be identified.

PMID- 22155484
TI  - Amniotic mesenchymal stem cells have robust angiogenic properties and are
      effective in treating hindlimb ischaemia.
AB  - AIMS: In this study, we aimed to evaluate whether human amniotic mesenchymal stem
      cells (AMMs) have angio-vasculogenic properties and to determine their
      therapeutic effects on experimental ischaemia. Although AMMs are a promising
      source of stem cells, their angio-vasculogenic properties are not fully
      understood. METHODS AND RESULTS: We have characterized AMMs by quantitative real
      time polymerase chain reaction, Matrigel tube formation assays, and various in
      vitro endothelial differentiation assays. AMMs expressed significantly higher
      levels of representative proangiogenic genes, vascular endothelial growth factor
      A, angiopoietin-1, hepatocyte growth factor, and fibroblast growth factor-2 (FGF
      2) than adipose-derived mesenchymal stem cells. In addition, the anti-apoptotic
      factor Akt-1 was highly expressed in the AMMs. Cells were directly transplanted
      into the ischaemic hindlimbs of mice to evaluate their angio-vasculogenic and
      therapeutic effects. They spontaneously differentiate into vascular-like
      structures and exhibit endothelial-specific genes and proteins. In an in vivo
      study on hindlimb ischaemia, implantation of AMMS augmented blood perfusion and
      capillary density, indicating AMM-augmented neovascularization. The engraftment
      rate of AMMs was high, and the transplanted AMMs showed vasulogenic potential.
      CONCLUSION: AMMs are not only markedly angiogenic but also vasculogenic, thus
      ameliorating hindlimb ischaemia. Our data suggest that AMMs have considerable
      therapeutic effects on ischaemic hindlimb through high angiogenic and engraftment
      abilities.

PMID- 22155483
TI  - Blood serum miRNA: non-invasive biomarkers for Alzheimer's disease.
AB  - There is an urgent need to identify non-invasive biomarkers for the detection of
      sporadic Alzheimer's disease (AD). We previously studied microRNAs (miRNAs) in AD
      autopsy brain samples and reported a connection between miR-137, -181c, -9, 
      29a/b and AD, through the regulation of ceramides. In this study, the potential
      role of these miRNAs as diagnostic markers for AD was investigated. We identified
      that these miRNAs were down-regulated in the blood serum of probable AD patients.
      The levels of these miRNAs were also reduced in the serum of AD risk factor
      models. Although the ability of these miRNAs to conclusively diagnose for AD is
      currently unknown, our findings suggest a potential use for circulating miRNAs,
      along with other markers, as non-invasive and relatively inexpensive biomarkers
      for the early diagnosis of AD, however, with further research and validation.

PMID- 22155485
TI  - Use of 13 disease registries in 5 countries demonstrates the potential to use
      outcome data to improve health care's value.
AB  - As health care systems worldwide struggle with rising costs, a consensus is
      emerging to refocus reform efforts on value, as determined by the evaluation of
      patient outcomes relative to costs. One method of using outcome data to improve
      health care value is the disease registry. An international study of thirteen
      registries in five countries (Australia, Denmark, Sweden, the United Kingdom, and
      the United States) suggests that by making outcome data transparent to both
      practitioners and the public, well-managed registries enable medical
      professionals to engage in continuous learning and to identify and share best
      clinical practices. The apparent result: improved health outcomes, often at lower
      cost. For example, we calculate that if the United States had a registry for hip
      replacement surgery comparable to one in Sweden that enabled reductions in the
      rates at which these surgeries are performed a second time to replace or repair
      hip prostheses, the United States would avoid $2 billion of an expected $24
      billion in total costs for these surgeries in 2015.

PMID- 22155486
TI  - Uliginosin B, a phloroglucinol derivative from Hypericum polyanthemum: a
      promising new molecular pattern for the development of antidepressant drugs.
AB  - In this study we have demonstrated that cyclohexane extract of Hypericum
      polyanthemum (POL) and its main phloroglucinol derivative uliginosin B (ULI)
      present antidepressant-like activity in rodent forced swimming test (FST). The
      involvement of monoaminergic neurotransmission on the antidepressant-like
      activity of ULI was evaluated in vivo and in vitro. POL 90 mg/kg (p.o.) and ULI
      10 mg/kg (p.o.) reduced the immobility time in the mice FST without altering
      locomotion activity in the open-field test. The combination of sub-effective
      doses of POL (45 mg/kg, p.o.) and ULI (5 mg/kg, p.o.) with sub-effective doses of
      imipramine (10 mg/kg, p.o.), bupropion (3 mg/kg, p.o.) and fluoxetine (15 mg/kg,
      p.o.) induced a significant reduction on immobility time in FST. The pretreatment
      with SCH 23390 (15 MUg/kg, s.c., dopamine D1 receptor antagonist), sulpiride (50
      mg/kg, i.p., dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., alpha1
      adrenoceptor antagonist), yohimbine (1mg/kg, i.p., alpha2-adrenoceptor
      antagonist) and pCPA (100 mg/kg/day, i.p., p-chlorophenilalanine methyl ester,
      inhibitor of serotonin synthesis, for four consecutive days) before ULI
      administration (10 mg/kg, p.o.) significantly prevented the anti-immobility
      effect in FST. ULI was able to inhibit synaptosomal uptake of dopamine (IC50 = 90
      +/- 38 nM), serotonin (IC50 = 252 +/- 13 nM) and noradrenaline (280 +/- 48 nM),
      but it did not bind to any of the monoamine transporters. These data firstly
      demonstrated the antidepressant-like effect of POL and ULI, which depends on the
      activation of the monoaminergic neurotransmission in a different manner from the
      most antidepressants.

PMID- 22155487
TI  - Deletion of the Lsamp gene lowers sensitivity to stressful environmental
      manipulations in mice.
AB  - The Lsamp gene gives rise to limbic system-associated membrane protein (LAMP),
      which is expressed on the surface of somata and proximal dendrites of neurons.
      Lsamp-deficient mice have been shown to be slightly hyperactive in novel
      environments and less anxious, and they display alterations in swimming speed,
      fear reaction, fear conditioning and social behaviour. In human studies, links
      between the LSAMP gene and several psychiatric disorders have been found and
      LSAMP has been established as a tumour suppressor gene. To study the impact of
      environmental manipulations on the phenotype, we exposed male Lsamp-deficient
      mice to environmental enrichment (EE), a technique that has often been shown to
      abolish phenotypic deviations in knockout mice, and to social isolation, a
      stressful manipulation, after which all the mice were tested in a behavioural
      battery. EE abolished differences between the genotypes in body weight and
      anogenital sniffing, a behaviour related to aggressiveness, and amplified the
      anxiolytic-like phenotype of Lsamp-deficient mice both in the plus maze and
      motility box. Isolation abolished differences between the genotypes in body
      weight and anxiety and amplified the differences in swimming speed and anogenital
      sniffing. EE and isolation failed to modify the results as compared to standard
      housing in whisker trimming, locomotor activity, marble burying and
      corticosterone levels. In conclusion, Lsamp-deficient mice were less sensitive to
      isolation stress than their wild-type littermates. Lack of LAMP protein seemingly
      leads to a deterioration in the ability to adapt to novel stressful environments
      and stimuli.

PMID- 22155488
TI  - On the edge: pharmacological evidence for anxiety-related behavior in zebrafish
      larvae.
AB  - Zebrafish larvae are ideally suited for high-throughput analyses of vertebrate
      behavior. The larvae can be examined in multiwell plates and display a range of
      behaviors during early development. Previous studies have shown that zebrafish
      larvae display a preference for the edge of the well and several lines of
      evidence suggest this edge preference (thigmotaxis) may be a measure of anxiety.
      In the present study, we further examined the relation between edge preference
      and anxiety by imaging zebrafish larvae exposed to three psychoactive drugs
      diazepam (Valium), fluoxetine (Prozac), and caffeine. The edge preference was
      first examined in a five-fish assay, with and without visual stimuli. Diazepam, a
      benzodiazepine that binds to GABA receptors, reduced the larval edge preference,
      with or without visual stimuli. In contrast, fluoxetine, a selective serotonin
      reuptake inhibitor, did not affect the edge preference. Caffeine increased the
      preference for the edge in response to visual stimuli. Similar effects were
      observed in a two-fish assay; diazepam-exposed larvae showed a reduced edge
      preference and caffeine exposed larvae showed an increased edge preference. These
      results suggest that the edge preference in zebrafish larvae is a measure of
      anxiety and further illustrate that the pharmaceuticals used in the study have
      different mechanisms of action. Although there are substantial differences
      between zebrafish and human brains, our results indicate that the signals that
      regulate anxiety are similar on a molecular level. We propose that high
      throughput assays in zebrafish may be used to uncover genetic or environmental
      factors that cause anxiety disorders and may contribute to the development of
      novel strategies to prevent or treat such disorders.

PMID- 22155489
TI  - The effects of working memory resource depletion and training on sensorimotor
      adaptation.
AB  - We have recently demonstrated that visuospatial working memory performance
      predicts the rate of motor skill learning, particularly during the early phase of
      visuomotor adaptation. Here, we follow up these correlational findings with
      direct manipulations of working memory resources to determine the impact on
      visuomotor adaptation, a form of motor learning. We conducted two separate
      experiments. In the first one, we used a resource depletion strategy to
      investigate whether the rate of early visuomotor adaptation would be negatively
      affected by fatigue of spatial working memory resources. In the second study, we
      employed a dual n-back task training paradigm that has been shown to result in
      transfer effects [1] over five weeks to determine whether training-related
      improvements would boost the rate of early visuomotor adaptation. The depletion
      of spatial working memory resources negatively affected the rate of early
      visuomotor adaptation. However, enhancing working memory capacity via training
      did not lead to improved rates of visuomotor adaptation, suggesting that working
      memory capacity may not be the factor limiting maximal rate of visuomotor
      adaptation in young adults. These findings are discussed from a resource
      limitation/capacity framework with respect to current views of motor learning.

PMID- 22155490
TI  - 'Post-lunch' sleepiness during prolonged, monotonous driving - effects of meal
      size.
AB  - The 'post-lunch' dip is a bi-circadian phenomenon, largely unrelated to lunch,
      and worsened by a disturbed prior night's sleep. Despite anecdotal claims of
      adverse effects of larger lunches on afternoon driving ability, there is little
      actual driving data to support this belief. Although there have been various (non
      driving) laboratory studies assessing meal size and micronutrient effects on
      psychological performance tests, findings are mixed. Moreover, most have not
      utilised heightened afternoon sleepiness after a shortened night's sleep, and few
      tested beyond 20 min. Using a real car interactive simulator having full size
      screen projection, we compared the effects on a 2h monotonous afternoon drive, of
      two very similar, palatable lunches ('light': 305 cal vs 'heavy': 922 cal [having
      3* fat and 2* carbohydrate contents]), given double blind in a repeated measures
      counterbalanced design, to 12 young male drivers whose prior night's sleep had
      been restricted to 5h. Sleepiness-related lane drifting ('incidents'), subjective
      sleepiness and EEG (4-11 Hz power - indicative of sleepiness) were logged
      throughout. The heavy lunch caused significant increases to both incidents and
      EEG power, and a trend for greater subjective sleepiness. All three indices
      showed a significant worsening of sleepiness over the drive under both lunch
      conditions. Whilst there were no significant condition*time interactions, there
      was no difference between lunches for at least the first 30 min of the drive
      when, thereafter, the differences appeared. Ours was a realistic driving study,
      utilising typical lunches, following an unexceptional level of prior sleep loss,
      and where a heavy lunch exacerbated inherent sleepiness, to further impair
      monotonous driving.

PMID- 22155491
TI  - Neonatal maternal separation in male rats increases intestinal permeability and
      affects behavior after chronic social stress.
AB  - Prolonged maternal separation in rats has several effects on health and behavior.
      Here we investigated how maternal separation might interact with social stress in
      adulthood on behavior and gastrointenstinal permeability. The effects of either
      daily 180 min long term pup-dam separation (LMS) during the stress hyporesponsive
      period or daily 10 min brief maternal separation (BMS) on behavior,
      corticosterone and intestinal permeability were investigated, compared to a non
      handling (NH) condition in male offspring. The animals from each separation
      condition were then randomly assigned to adult stress and control conditions,
      where the stress condition was exposure to 14 days of social instability (CSI).
      Sucrose preference, elevated plus maze behavior and corticosterone were measured.
      Colitis was experimentally induced by dextran sulfate sodium for 7 days, followed
      by measurement of intestinal permeability using the (51)CrEDTA method.
      Granulocyte marker protein was measured in feces and colons were examined
      histologically for inflammation. Prior to the social stress, the LMS offspring
      showed elevated corticosterone levels, lower elevated plus maze activity and less
      fluid consumption. After social stress, corticosterone levels were suppressed in
      LMS animals and again they showed less fluid consumption. LMS animals had
      significantly higher intestinal permeability, but only when also exposed to the
      social stress in adulthood. The current results support a two-hit model, whereby
      early life events interact with adult life events in altering animals'
      vulnerability.

PMID- 22155492
TI  - The intricate link between glucocorticoids and endocannabinoids at stress
      relevant synapses in the hypothalamus.
AB  - The relationship between glucocorticoids and endocannabinoids at hypothalamic
      synapses in the presence of stress is particularly complex. Under conditions of
      acute stress, glucocorticoids trigger the synthesis of endocannabinoids, which
      through activation of type I cannabinoid receptors (CB1Rs), inhibit stress
      relevant neurons in the paraventricular nucleus of the hypothalamus (PVN).
      Through this signaling mechanism, endocannabinoids constrain the activity of the
      hypothalamic-pituitary-adrenal axis. However, following chronic or repeated
      stress, the ability of endocannabinoids to modulate synaptic activity is
      compromised because of a functional down-regulation in CB1Rs. Here we examine
      recent findings that highlight important aspects of endocannabinoid signaling in
      response to stress in the PVN and the dorsomedial hypothalamus (DMH), two
      hypothalamic nuclei that play integral roles in regulating the neuroendocrine and
      autonomic responses to stress.

PMID- 22155493
TI  - Cell type-specific localization of optineurin in the striatal neurons of mice:
      implications for neuronal vulnerability in Huntington's disease.
AB  - Striatal neuropathology of Huntington's disease (HD) involves primary and
      progressive degeneration of the medium-sized projection neurons, with relative
      sparing of the local circuit interneurons. The mechanism for such a patterned
      cell loss in the HD striatum continues to remain unclear. Optineurin (OPTN) is
      one of the proteins interacting with huntingtin and plays a protective role in
      several neurodegenerative disorders. To determine the cellular localization
      pattern of OPTN in the mouse striatum, we employed a highly sensitive
      immunohistochemistry with the tyramide signal amplification system. In this
      study, we show that OPTN appeared as a cytoplasmic protein within the subsets of
      the striatal neurons. Of particular interest was that OPTN was abundantly
      expressed in the interneurons, whereas low levels of OPTN were observed in the
      medium projection neurons. This cell type-specific distribution of OPTN in the
      striatum is strikingly complementary to the pattern of neuronal loss typically
      observed in the striatum of patients with HD. We suggest that OPTN abundance is
      an important cellular factor in considering the cell type-specific vulnerability
      of striatal neurons in HD.

PMID- 22155494
TI  - Cytotoxic T lymphocyte antigen 4 immunogloblin promotes neuronal differentiation
      in the grafts of embryonic stem cell-derived neural precursor cells.
AB  - For safe and efficient transplantation of embryonic stem cells (ESCs), it is
      important to reduce inflammatory and immune response by the host brain. Full
      activation of T cells in response to donor antigen requires the delivery of two
      separate but complimentary signals not only via T cell receptor following
      recognition of antigen, but also via antigen-nonspecific ligation of the
      costimulatory receptor-ligand pairs such as CD28:CD80/86. Cytotoxic T lymphocyte
      antigen 4 (CTLA4), structurally related to CD28, delivers an inhibitory signal
      after ligation to CD80/86, resulting in the termination of T cell immune
      responses. To investigate the role of this pathway in the survival and
      differentiation of neural progenitor cells (NPCs) from mouse ESCs, we
      transplanted the NPCs into mouse brains with or without CTLA4 immunogloblin
      (CTLA4-Ig). Immunohistochemical studies revealed that accumulation of
      inflammatory/immune cells in and around the graft was reduced by CTLA4-Ig. In
      contrast, the percentage of neurons in the graft was increased. These results
      suggest that CTLA4-Ig may promote neuronal differentiation during the treatment
      of neurological diseases with cell replacement therapy.

PMID- 22155495
TI  - Activation of the brainstem precedes and outlasts the K-complex in humans.
AB  - A K-complex (KC) in the electroencephalographs (EEGs) indicates a moderate depth
      of slow-wave sleep (SWS) in humans and animals. The cortical activities are
      upregulated during the periods between the KCs ("up state"), and it is proposed
      that temporarily stored memories during wakeful periods will be consolidated
      during these periods. Although the underlying mechanism for KCs is proposed to be
      in the cortex itself, the involvement of the brainstem has not been explored.
      Here we investigate the excitability changes of the brainstem preceding, during,
      and after KCs in humans. We simultaneously recorded brainstem auditory evoked
      potentials (BAEPs) with EEGs, and sequentially analyzed BAEPs around the KCs. The
      results showed a transient activation of the ventral brainstem preceding the KC
      and a sustained activation of the dorsal brainstem outlasting the KC. Thus, it is
      suggested that KCs are triggered by the activation of the brainstem and that the
      "up state" is maintained by the sustained activation of the brainstem.

PMID- 22155496
TI  - How do we continue to attract the best candidates to the surgical profession?

PMID- 22155497
TI  - Non-histone lysine acetylated proteins in heart failure.
AB  - Both histone-acetylations and histone deacetylases have been shown to play a key
      role in cardiac remodeling. Recently, it has become abundantly clear that many
      non-histone proteins are modified by post-translational lysine acetylations and
      that these acetylations regulate protein activity, conformation, and binding. In
      the present study, non-histone acetylated proteins associated with heart failure
      were identified. Global screening for lysine acetylated proteins was performed
      using 2-dimensional gel electrophoresis coupled with immunoblotting with a
      primary monoclonal anti-acetyl-lysine antibody. Lysine acetylated proteins were
      compared in two rodent models of hypertensive heart failure, the Dahl salt
      sensitive (SS) and spontaneously hypertensive heart failure prone (SHHF) rats
      with those in corresponding controls, i.e., the Dahl salt-resistant (SR) and W
      (W) rat strains, respectively. Forty-one and 66 acetylated proteins were detected
      in SS and SHHF failing hearts, respectively, but either not detected or detected
      with less abundance in corresponding control hearts. Twelve of these acetylated
      proteins were common to both models of heart failure. These were identified using
      matrix-assisted laser desorption/ionization time of flight (MALDI-TOF/TOF) mass
      spectrometry followed by Mascot Analysis and included mitochondrial enzymes: ATP
      synthase, long-chain acyl-CoA dehydrogenase, creatine kinase, malate
      dehydrogenase, and pyruvate dehydrogenase. The abundance of NAD-dependent
      deacetylase sirtuin-3 (Sirt3), a mitochondrial deacetylase was reduced in SS and
      SHHF failing hearts. This is the first description of non-histone protein
      acetylations associated with heart failure and raises the prospect that
      acetylations of mitochondrial proteins linked to reduced Sirt3 mediate, in part,
      metabolic changes in heart failure.

PMID- 22155498
TI  - Prenatal alcohol exposure alters the course and severity of adjuvant-induced
      arthritis in female rats.
AB  - Prenatal alcohol exposure (PAE) has adverse effects on the development of
      numerous physiological systems, including the hypothalamic-pituitary-adrenal
      (HPA) axis and the immune system. HPA hyper-responsiveness and impairments in
      immune competence have been demonstrated. The present study investigated immune
      function in PAE females utilizing an adjuvant-induced arthritis (AA) model,
      widely used as a model of human rheumatoid arthritis. Given the effects of PAE on
      HPA and immune function, and the known interaction between HPA and immune systems
      in arthritis, we hypothesized that PAE females would have heightened autoimmune
      responses, resulting in increased severity of arthritis, compared to controls,
      and that altered HPA activity might play a role in the immune system changes
      observed. The data demonstrate, for the first time, an adverse effect of PAE on
      the course and severity of AA in adulthood, indicating an important long-term
      alteration in functional immune status. Although overall, across prenatal
      treatments, adjuvant-injected animals gained less weight, and exhibited decreased
      thymus and increased adrenal weights, and increased basal levels of
      corticosterone and adrenocorticotropin, PAE females had a more prolonged course
      of disease and greater severity of inflammation compared to controls. In
      addition, PAE females exhibited blunted lymphocyte proliferative responses to
      concanavalin A and a greater increase in basal ACTH levels compared to controls
      during the induction phase, before any clinical signs of disease were apparent.
      These data suggest that prenatal alcohol exposure has both direct and indirect
      effects on inflammatory processes, altering both immune and HPA function, and
      likely, the normal interactions between these systems.

PMID- 22155499
TI  - Age related changes in microglial phenotype vary between CNS regions: grey versus
      white matter differences.
AB  - Subtle regional differences in microglial phenotype exist in the adult mouse
      brain. We investigated whether these differences were amplified during ageing and
      following systemic challenge with lipopolysaccharide (LPS). We studied microglial
      morphology and phenotype in young (4mo) and aged (21mo) C57/BL6 mice using
      immunohistochemistry and quantified the expression levels of surface molecules on
      microglia in white and grey matter along the rostral-caudal neuraxis. We detected
      significant regional, age dependent differences in microglial phenotypes, with
      the microglia of white matter and caudal areas of the CNS exhibiting greater
      upregulation of CD11b, CD68, CD11c, F4/80 and FcgammaRI than grey matter and
      rostral CNS areas. Upregulation of CD11c with age was restricted to the white
      matter, as was the appearance of multinucleated giant cells. Systemic LPS caused
      a subtle upregulation of FcgammaRI after 24 h, but the other markers examined
      were not affected. Burrowing behaviour and static rod assays were used to assess
      hippocampal and cerebellar integrity. Aged mice exhibited exaggerated and
      prolonged burrowing deficits following systemic LPS injection, while in the
      absence of an inflammatory challenge aged mice performed significantly worse than
      young mice in the static rod test. Taken together, these findings show that the
      effects of age on microglial phenotype and functional integrity vary
      significantly between CNS compartments, as do, albeit to a lesser extent, the
      effects of systemic LPS.

PMID- 22155500
TI  - Inflammation and reactivation of latent herpesviruses in older adults.
AB  - Inflammation increases with age and is associated with many chronic diseases that
      are prevalent among older adults. Persistent pathogens such as latent
      herpesviruses and chronic bacterial infections can act as a source of
      inflammation. Herpesviruses, including Epstein-Barr virus (EBV) and
      cytomegalovirus (CMV), establish latent infections following primary infection
      and reactivate when the cellular immune system is compromised. EBV and CMV
      replication can induce proinflammatory cytokine production and thus could
      influence systemic inflammation. The present study addressed relationships among
      EBV and CMV antibody titers, and levels of C-reactive protein (CRP) and
      interleukin-6 (IL-6) in a sample of 222 community dwelling older adults
      (mean(age)=64.1+/-14.1 years). Participants were divided into two groups based on
      whether they were EBV seropositive and CMV seronegative (EBV+CMV-), or EBV and
      CMV seropositive (EBV+CMV+). Among individuals who were EBV+CMV-, EBV antibody
      titers were not associated with either CRP or IL-6 levels. However, among those
      who were EBV+CMV+, higher EBV antibody titers were related to elevated levels of
      CRP and IL-6 in those individuals with higher CMV antibody titers; there was no
      relationship between EBV antibody titers and CRP or IL-6 levels in those
      participants with lower CMV antibody titers. These data suggest that the
      combination of latent EBV and CMV reactivation (indexed by antibody titers) may
      boost CRP and IL-6 production. Thus, reactivation of multiple herpesviruses may
      drive inflammation and could contribute to poorer health among older adults.

PMID- 22155501
TI  - Highly variable pharmacokinetics of once-daily intravenous busulfan when combined
      with fludarabine in pediatric patients: phase I clinical study for determination
      of optimal once-daily busulfan dose using pharmacokinetic modeling.
AB  - Busulfan has a narrow therapeutic range, and in children, pharmacokinetic
      variability has been found to be high even after the use of intravenous (i.v.)
      busulfan. Recently, a reduced toxicity myeloablative regimen showed promising
      results, but the data of busulfan pharmacokinetics in hematopoietic stem cell
      transplantation (HSCT) using a targeted busulfan/fludarabine regimen in children
      has not yet been reported. We performed therapeutic drug monitoring (TDM) after
      once-daily i.v. busulfan combined with fludarabine and analyzed the outcomes.
      Busulfan (i.v.) was administered once daily for 4 consecutive days. The daily
      target area under the curve (AUC) was 18,125-20,000 MUg*h/L/day (4415-4872
      MUmol*min/L/day), which was reduced to 18,000-19,000 MUg*h/L/day (4384-4628
      MUmol*min/L/day) after a high incidence of toxicity was observed. A total of 24
      patients were enrolled. After infusion of busulfan on the first day, patients
      showed AUC that ranged from 12,079 to 31,660 MUg*h/L (2942 to 7712 MUmol*min/L)
      (median 16,824 MUg*h/L, percent coefficient of variation (%CV) = 26.5%), with
      clearance of 1.74-6.94 mL/min/kg (median 4.03 mL/min/kg). We performed daily TDM
      in 20 patients, and during the daily TDM, the actual AUC ranged from 73% to 146%
      of the target AUC, showing high intraindividual variability. The %CV of busulfan
      clearance of each individual ranged from 7.7% to 38.7%. The total dose of
      busulfan administered for 4 days ranged from 287.3 mg/m(2) to 689.3 mg/m(2).
      Graft failure occurred in 3 patients with total AUC less than 74,000 MUg*h/L
      (18,026 MUmol*min/L), and 2 patients with relatively high total AUC experienced
      veno-occlusive disease. Busulfan pharmacokinetics showed high inter- and
      intraindividual variability in HSCT using a targeted busulfan/fludarabine
      regimen, which indicates the need for intensive monitoring and dose adjustment to
      improve the outcome of HSCT. Currently, we are performing a newly designed phase
      II study to decrease regimen-related toxicities and reduce graft failure by
      setting an optimal target AUC based on this study.

PMID- 22155503
TI  - My AML cytogenetics classification scheme is better than yours.

PMID- 22155504
TI  - Important drug interactions in hematopoietic stem cell transplantation: what
      every physician should know.
AB  - Morbidity is increased in patients undergoing hematopoietic stem cell
      transplantation when drug-drug interactions lead to unexpected outcomes. These
      interactions occur as a result of exposure to complicated medical regimens with
      drugs with narrow therapeutic windows and high toxicity profiles. In this report,
      we review the available evidence and possible mechanisms of the most clinically
      relevant drug interactions, including those involving inhibitors and inducers of
      the P450 isoenzyme system. We identify key interactions that should be familiar
      to any physician caring for patients after hematopoietic stem cell
      transplantation. We discuss drug metabolism in children and in the elderly and
      examine how age-related differences in metabolism make complicate drug regimens
      in these populations. A better understanding of these interactions and the
      responsible mechanisms will promote efficient delivery of the safest medical
      regimens to patients undergoing hematopoietic stem cell transplantation.

PMID- 22155502
TI  - Natural killer cell differentiation from hematopoietic stem cells: a comparative
      analysis of heparin- and stromal cell-supported methods.
AB  - Natural killer (NK) cells differentiated from hematopoietic stem cells (HSCs) may
      have significant clinical benefits over NK cells from adult donors, including the
      ability to choose alloreactive donors and potentially more robust in vivo
      expansion. Stromal-based methods have been used to study the differentiation of
      NK cells from HSCs. Stroma and cytokines support NK cell differentiation, but may
      face considerable regulatory hurdles. A recently reported clinical-grade, heparin
      based method could serve as an alternative. How the stromal-based and heparin
      based approaches compare in terms of NK cell generating efficiency or function is
      unknown. We show that compared with heparin-based cultures, stroma significantly
      increases the yield of HSC-derived NK cells by differentiating less-committed
      progenitors into the NK lineage. NK cells generated by both approaches were
      similar for most NK-activating and -inhibiting receptors. Although both
      approaches resulted in a phenotype consistent with CD56(bright) stage IV NK
      cells, heparin-based cultures favored the development of CD56(+)CD16(+) cells,
      whereas stroma produced more NK cell immunoglobulin-like receptor-expressing NK
      cells, both of which are markers of terminal maturation. At day 21, stromal-based
      cultures demonstrated significantly more IL-22 production, and both methods
      yielded similar amounts of IFN-gamma production and cytotoxicity by day 35. These
      findings suggest that heparin-based cultures are an effective replacement for
      stroma and may facilitate clinical trials testing HSC-derived NK cells.

PMID- 22155505
TI  - T cell-depleted partial matched unrelated donor transplant for advanced myeloid
      malignancy: KIR ligand mismatch and outcome.
AB  - To evaluate the applicability of high-dose conditioning, CD34 selection, and
      enhanced natural killer (NK) cell alloreactivity reported as promising after
      haploidentical transplantation, we tested the same strategy for patients with
      advanced/high-risk myeloid leukemia lacking either related or well-matched
      unrelated donors (URD). In a prospective multicenter clinical trial using
      pretransplantation conditioning of thiotepa (5 mg/kg/day * 2), fludarabine (40
      mg/mg/M(2)/day * 5), and total body radiation (800 cGy) plus thymoglobulin (2.5
      mg/kg/day * 2), as well as a CD34 selected filgrastim stimulated peripheral blood
      graft from a partial matched URD, we treated 24 patients. The patients (median
      age 40 [range: 22-61]) were mismatched at 1-3 of 10 HLA loci with their donors;
      all were mismatched at HLA-C. Thirty-seven percent were ethnic or racial
      minorities. Twenty-one of 24 engrafted promptly with 1 primary graft failure and
      2 early deaths. The cumulative incidence of grade II-IV acute graft-versus-host
      disease (aGVHD) (34%, 95% confidence interval [CI], 14-54%), chronic GVHD (20%,
      95% CI, 2%-38%), and relapse (26%, 95% CI, 8%-84%) were unaffected by KIR ligand
      donor:recipient mismatch (n = 5) versus KIR ligand match (n = 19). Only 3 (12%)
      had grade III-IV GVHD. Nonrelapse occurred in 17% (95% CI, 30%-31%) by 100 days
      and in 35% (95% CI, 15%-55%) by 1 year. Two-year survival and leukemia-free
      survival were each 40% (95% CI, 21%-59%) and was similar in KIR ligand matched or
      mismatched patients. Infections, mostly in the first 2 months, were frequent, and
      were the cause of death in 5 patients (35% of deaths). T cell recovery and NK
      cell proliferation and functional maturation were not altered by KIR ligand match
      or mismatch status. For these high-risk patients, this high intensity regimen and
      T depleted approach yielded satisfactory outcomes, but logistical difficulties in
      arranging URD grafts for patients with high-risk, unstable leukemia limited
      accrual. Improvements in peritransplantation disease control and additional
      measures to augment the allogeneic graft-versus-leukemia effect are still
      required.

PMID- 22155506
TI  - Alternate donor hematopoietic cell transplantation (HCT) in non-Hodgkin lymphoma
      using lower intensity conditioning: a report from the CIBMTR.
AB  - We analyzed the outcomes of 248 (61% male) adult recipients of HLA-matched
      unrelated and HLA-mismatched related donor hematopoietic cell transplantation
      (HCT) for non-Hodgkin lymphoma (NHL) after reduced or lower intensity
      conditioning (RIC), reported to the Center for International Blood and Marrow
      Transplant Research (CIBMTR) from 1997 to 2004. Median age was 52 (range: 18-72
      years); 31% had a Karnofsky performance score <90. Follicular NHL (43%) was the
      major histology. Incidence of grades II-IV acute graft-versus-host disease
      (aGVHD) was 43% at 100 days; and chronic GVHD (cGVHD) was 44% at 3 years.
      Treatment-related mortality (TRM) at 100 days was 24%. Three-year overall
      survival (OS) and progression-free survival (PFS) were 41% and 32%, respectively.
      In multivariate analysis, use of antithymocyte globulin (ATG) and HLA mismatch
      were associated with increased TRM. High-grade histology, ATG use, and
      chemotherapy resistance were associated with lower PFS. Older age, shorter
      interval from diagnosis to HCT, non-total body irridiation (TBI) conditioning
      regimens, ex vivo T cell depletion, and HLA-mismatched unrelated donors were
      associated with mortality. GVHD did not influence relapse or PFS. Older age,
      aggressive histology, and chemotherapy resistance correlated with poorer
      survival. For selected patients with NHL, lack of an available sibling donor
      should not be a barrier to allogeneic HCT.

PMID- 22155507
TI  - Tandem autologous-allogeneic nonmyeloablative sibling transplantation in relapsed
      follicular lymphoma leads to impressive progression-free survival with minimal
      toxicity.
AB  - Autologous stem cell transplantation (ASCT) prolongs survival in patients with
      relapsed follicular lymphoma. ASCT is usually not curative, however.
      Myeloablative allogeneic transplantation has produced long-term survival at a
      cost of significant transplantation-related mortality (TRM), whereas reduced
      intensity transplantation entails less TRM but has a higher relapse rate. We thus
      initiated a protocol consisting of ASCT followed by nonmyeloablative allogeneic
      transplantation (NMT) for relapsed follicular lymphoma to mimic myeloablative
      allogeneic transplantation without the associated toxicity. The NMT was non-T
      cell-depleted, and all donors were HLA-identical siblings. We report results in
      27 patients with a median age of 49 years (range, 34-65 years). Five patients
      demonstrated histological progression toward an aggressive lymphoma. The patients
      had received a median of 3 lines of previous therapy. Disease status before ASCT
      included 8 patients in complete remission, 14 in partial remission, and 5
      refractory. Five patients developed grade II-IV acute graft-versus-host disease,
      and 20 patients developed chronic graft-versus-host disease requiring systemic
      therapy. With a median follow-up of 39 months after NMT, overall survival and
      progression-free survival were 96% at 3 years. We conclude that the combined ASCT
      NMT strategy appears to be safe, with excellent progression-free survival even in
      refractory and transformed cases. This novel approach warrants further
      investigation in larger prospective studies.

PMID- 22155508
TI  - Ucma is not necessary for normal development of the mouse skeleton.
AB  - Ucma (Upper zone of growth plate and Cartilage Matrix Associated protein) is a
      highly conserved tyrosine-sulphated secreted protein of Mw 17 kDa, which is
      expressed by juvenile chondrocytes. To evaluate the physiological function of
      this novel cartilage protein, we generated a Ucma-deficient mouse strain by
      introducing a lacZ/neoR-cassette into the first exon of the Ucma gene. This
      mutation results in the complete loss of Ucma mRNA and protein expression.
      Surprisingly, however, although previous in vitro studies implied a role for Ucma
      in calcification and ossification, these processes were not affected in Ucma
      deficient mice during normal development. Likewise, cartilage development was
      normal. While in previous works Ucma was mainly detected in the cartilage of
      embryonic and young mice, we detected Ucma expression also in the adult cartilage
      of the ribs using the lacZ cassette under the control of the Ucma promoter.
      Moreover, Ucma protein was specifically detected in adult growth plate cartilage
      by immunohistochemistry. Considering that skeletal development in Ucma-deficient
      mice is not significantly impaired, protein expression in adult cartilage
      indicates that Ucma might be involved in skeletal homeostasis and in the
      mechanical properties of the skeleton during challenging conditions such as
      ageing or disease.

PMID- 22155509
TI  - Molecular characterisation of the Hyp deletion and an improved assay for its
      detection.
AB  - The Hyp mouse is a commonly used model for the study of the phosphate wasting
      disease X-linked hypophosphataemia. The defect in this mouse line is a deletion
      that includes exons 16 to 22 of Phex, although the exact extent of this X
      chromosome deletion remains unknown. This complicates genotyping which increases
      costs, time and difficulty of working with this important model. We aimed to
      determine the molecular breakpoints of this deletion in order develop a robust
      assay for its detection. We designed short mapping PCRs around the Phex locus to
      refine the putative breakpoint locations, then used gap PCR to amplify a product
      containing the breakpoint junction. DNA sequencing showed the deleted region was
      approximately 297 kb, significantly larger than previous reports, but did not
      contain any genes other than Phex. DNA sequence analysis revealed that this
      deletion may be the result of microhomology-mediated end joining. Finally, we
      designed a multiplex PCR assay for genotyping Hyp colonies and validated it using
      a panel of Hyp colony mice. This study provides confirmation of the Hyp phenotype
      as a single gene defect, a potential mechanism for its formation and an improved
      method for genotyping that will make working with this strain significantly
      easier.

PMID- 22155510
TI  - Botulinum toxin in masticatory muscles: short- and long-term effects on muscle,
      bone, and craniofacial function in adult rabbits.
AB  - Paralysis of the masticatory muscles using botulinum toxin (BTX) is a common
      treatment for cosmetic reduction of the masseters as well as for conditions
      involving muscle spasm and pain. The effects of this treatment on mastication
      have not been evaluated, and claims that the treatment unloads the jaw joint and
      mandible have not been validated. If BTX treatment does decrease mandibular
      loading, osteopenia might ensue as an adverse result. Rabbits received a single
      dose of BTX or saline into one randomly chosen masseter muscle and were followed
      for 4 or 12 weeks. Masticatory muscle activity was assessed weekly, and incisor
      bite force elicited by stimulation of each masseter was measured periodically. At
      the endpoint, strain gages were installed on the neck of the mandibular condyle
      and on the molar area of the mandible for in vivo bone strain recording during
      mastication and muscle stimulation. After termination, muscles were weighed and
      mandibular segments were scanned with micro CT. BTX paralysis of one masseter did
      not alter chewing side or rate, in part because of compensation by the medial
      pterygoid muscle. Masseter-induced bite force was dramatically decreased.
      Analysis of bone strain data suggested that at 4 weeks, the mandibular condyle of
      the BTX-injected side was underloaded, as were both sides of the molar area. Bone
      quantity and quality were severely decreased specifically at these underloaded
      locations, especially the injection-side condylar head. At 12 weeks, most
      functional parameters were near their pre-injection levels, but the injected
      masseter still exhibited atrophy and percent bone area was still low in the
      condylar head. In conclusion, although the performance of mastication was only
      minimally harmed by BTX paralysis of the masseter, the resulting underloading was
      sufficient to cause notable and persistent bone loss, particularly at the
      temporomandibular joint.

PMID- 22155512
TI  - Human nutrigenomics of gene regulation by dietary fatty acids.
AB  - Nutrigenomics employs high-throughput genomics technologies to unravel how
      nutrients modulate gene and protein expression and ultimately influence cellular
      and organism metabolism. The most often-applied genomics technique so far is
      transcriptomics, which allows quantifying genome-wide changes in gene expression
      of thousands of genes at the same time in one sample. The performance of gene
      expression quantification requires sufficient high-quality homogenous cellular
      material, therefore research in healthy volunteers is restricted to biopsies from
      easy accessible tissues such as subcutaneous adipose tissue, skeletal muscle and
      intestinal biopsies or even more easily accessible cells such as peripheral blood
      mononuclear cells from blood. There is now significant evidence that fatty acids,
      in particular unsaturated fatty acids, exert many of their effects through
      modulation of gene transcription by regulating the activity of numerous
      transcription factors, including nuclear receptors such as peroxisome
      proliferator activated receptors, liver X receptor and sterol regulatory binding
      proteins. This review evaluates the human nutrigenomics studies performed on
      dietary fat since the initiation of nutrigenomics research around 10 years ago.
      Although the number of studies is still limited, all studies clearly suggest that
      changes in dietary fatty acids intake and composition can have a significant
      impact on cellular adaptive response capacity by gene transcription changes in
      humans. This adds important knowledge to our understanding of the strong effects
      that various fatty acids can have on numerous metabolic and inflammatory
      pathways, signaling routes and homeostatic control in the cell and ultimately on
      whole body health. It is important to use and integrate nutrigenomics in all
      future nutrition studies to build up the necessary framework for evidence-based
      nutrition in near future.

PMID- 22155511
TI  - TGF-beta regulates sclerostin expression via the ECR5 enhancer.
AB  - Wnt signaling is critical for skeletal development and homeostasis. Sclerostin
      (Sost) has emerged as a potent inhibitor of Wnt signaling and, thereby, bone
      formation. Thus, strategies to reduce sclerostin expression may be used to treat
      osteoporosis or non-union fractures. Transforming growth factor-beta (TGF-beta)
      elicits various effects upon the skeleton both in vitro and in vivo depending on
      the duration and timing of administration. In vitro and in vivo studies
      demonstrate that TGF-beta increases osteoprogenitor differentiation but decreases
      matrix mineralization of committed osteoblasts. Because sclerostin decreases
      matrix mineralization, this study aimed to examine whether TGF-beta achieves such
      inhibitory effects via transcriptional modulation of Sost. Using the UMR106.01
      mature osteoblast cell line, we demonstrated that TGF-betaTGF-beta(1)-beta(2)
      beta(3) and Activin A increase Sost transcript expression. Pharmacologic
      inhibition of Alk4/5/7 in vitro and in vivo decreased endogenous Sost expression,
      and siRNA against Alk4 and Alk5 demonstrated their requirement for endogenous
      Sost expression. TGF-beta(1) targeted the Sost bone enhancer ECR5 and did not
      affect the transcriptional activity of the endogenous Sost promoter. These
      results indicate that TGF-beta(1) controls Sost transcription in mature
      osteoblasts, suggesting that sclerostin may mediate the inhibitory effect of TGF
      beta upon osteoblast differentiation.

PMID- 22155513
TI  - Genetic and antigenic characterization of small ruminant lentiviruses circulating
      in Poland.
AB  - Small ruminant lentivirus (SRLV) infections are widespread in Poland, but the
      genetic features of sheep viruses are still lacking and limited to partial gag
      sequences for goat viruses. In this study, segments from the gag and env genes of
      Polish SRLV strains screened by heteroduplex mobility assay were subjected to
      genetic analyses. Subtype A1 was found in both sheep and goats, while subtypes B1
      and B2 were found in goats and sheep, respectively. In addition, two novel
      subtypes (named A12 and A13) were found in sheep. Their close phylogenetic
      relatedness with SRLV strains previously isolated from Polish goats indicated
      that these new subtypes are predominant and circulate in both species. The
      antigenic relationships of subtypes A12 and A13 with other SRLV subtypes were
      tested in an ELISA assay based on recombinant antigens carrying the
      immunodominant domains of structural proteins (MA, CA and SU). Antigenic cross
      reactivity in the Gag epitopes was evident among genotype A subtypes and, to a
      lower extent, between genotypes A and B. In contrast, a subtype-specific
      immunoresponse was detected in the SU epitopes. These results emphasize the broad
      genetic and antigenic diversity of SRLV strains circulating in Europe and
      confirmed the need to consider all viral genotypes to choose the antigens in
      serological tests in order to avoid misdiagnosis in control and eradication
      programs.

PMID- 22155514
TI  - [Nobel prize in medicine, 2011].

PMID- 22155515
TI  - [Digestive system endoscopy in the elderly and in patients with severe
      comorbidities].
AB  - Besides the technical equipment, the endoscopic team's theoretical and practical
      skills, the success of endoscopic intervention is influenced by the patient's
      general condition. Advanced age, severe co-morbidities may increase the risk,
      especially in case of operative endoscopy. The decision is more complicated when
      alarm symptoms urge the examination. The endoscopic examination of digestive
      system, biliary track and pancreas in advanced age can safely be performed as
      alternatives of surgical intervention. It is important to know the exact stage of
      cardiovascular and pulmonary diseases, besides, in case of stroke the patient's
      cooperation is very important. In everyday practice the most common problems are
      the endoscopic examination of the patient in oral anticoagulant and/or
      thrombocyte aggregation inhibition therapy and the question of suspending,
      modifying or restarting the therapy. Examining the patients with implanted
      electronic device as well as antibiotic prophylaxis in expanding range of
      indications are special issues. The gastroenterologist makes the decision based
      on the knowledge of the endoscopic intervention, the patient's risk
      classification, the indications, the contradictions and the alternative
      diagnostic possibilities. This review attempts to give an overview with some
      practical aspects.

PMID- 22155516
TI  - [Role of R classification in the interdisciplinary oncology].
AB  - The R classification describes the tumor status after therapy. Many clinicians
      and pathologists use the definition in a misunderstood or wrong way, and
      sometimes, despite many recommendations this definition is not used in the daily
      routine, at all. The R status means not only the tumorous infiltration of the
      surgical margins but also includes the lymph node status and the metastases. It
      represents the whole tumorous process giving the most reliable prognostic marker.
      It is important for colleagues working in the same therapeutic group that the R
      status defined by pathologists has to mean the same consequences. This article
      shows how the R classification can be used in the daily routine and how someone
      can solve the misunderstandings in different R categories.

PMID- 22155517
TI  - [Role of patient safety in the official approval of new surgical techniques and
      devices].
AB  - Health technological industry brings every year thousands of new devices to the
      market worldwide. However, there is a large gap between the process of device
      approval and the control after release. Although, drugs can be used in health
      care only if they underwent randomized placebo controlled trials there are only a
      few devices that had similar studies. Surgery is a dangerous part of medicine and
      new technologies can represent hazard for patient safety.

PMID- 22155518
TI  - [Congenital disorders. Hydrocephalus].

PMID- 22155519
TI  - [Congenital disorders. Microcephaly].

PMID- 22155520
TI  - [Congenital disorders. Holoprosencephalia].

PMID- 22155521
TI  - [Remembering Arpad Nemeth (1941-1993)].

PMID- 22155523
TI  - Chronic cough in a tsunami-affected town.

PMID- 22155524
TI  - Next-generation sequencing technologies for gene expression profiling in plants.
AB  - Next-generation sequencing (NGS) provides a better approach to gene expression
      profiling with several advantages. The power of NGS along with novel molecular
      techniques and computational tools allow the researchers to perform the gene
      expression profiling to reveal transcriptional complexity of an organism and
      answering several biological questions. Although many studies for gene expression
      profiling related to various aspects have been performed in animal systems
      revealing unprecedented levels of complexity of transcriptomes, their use is
      still limited in plant biology. This review describes the use of NGS technologies
      with respect to gene expression profiling, bioinformatics challenges associated
      with data analysis and advances made so far in the plant biology research. We
      anticipate many more studies in recent future, which will surely advance our
      understanding of the complexity of plant genomes.

PMID- 22155525
TI  - Select microRNAs are essential for early development in the sea urchin.
AB  - microRNAs (miRNAs) are small noncoding RNAs that mediate post-transcriptional
      gene regulation and have emerged as essential regulators of many developmental
      events. The transcriptional network during early embryogenesis of the purple sea
      urchin, Strongylocentrotus purpuratus, is well described and can serve as an
      excellent model to test functional contributions of miRNAs in embryogenesis. We
      examined the loss of function phenotypes of major components of the miRNA
      biogenesis pathway. Inhibition of de novo synthesis of Drosha and Dicer in the
      embryo led to consistent developmental defects, a failure to gastrulate, and
      embryonic lethality, including changes in the steady state levels of
      transcription factors and signaling molecules involved in germ layer
      specification. We annotated and profiled small RNA expression from the ovary and
      several early embryonic stages by deep sequencing followed by computational
      analysis. miRNAs as well as a large population of putative piRNAs (piwi
      interacting RNAs) had dynamic accumulation profiles through early development.
      Defects in morphogenesis caused by loss of Drosha could be rescued with four
      miRNAs. Taken together our results indicate that post-transcriptional gene
      regulation directed by miRNAs is functionally important for early embryogenesis
      and is an integral part of the early embryonic gene regulatory network in S.
      purpuratus.

PMID- 22155526
TI  - A heat shock protein and Wnt signaling crosstalk during axial patterning and stem
      cell proliferation.
AB  - Both Wnt signaling and heat shock proteins play important roles in development
      and disease. As such, they have been widely, though separately, studied. Here we
      show a link between a heat shock protein and Wnt signaling in a member of the
      basal phylum, Cnidaria. A heat shock at late gastrulation in the clonal marine
      hydrozoan, Hydractinia, interferes with axis development, specifically inhibiting
      head development, while aboral structures remain unaffected. The heat treatment
      upregulated Hsc71, a constitutive Hsp70 related gene, followed by a transient
      upregulation, and long-term downregulation, of Wnt signaling components.
      Downregulating Hsc71 by RNAi in heat-shocked animals rescued these defects,
      resulting in normal head development. Transgenic animals, ectopically expressing
      Hsc71, had similar developmental abnormalities as heat-shocked animals in terms
      of both morphology and Wnt3 expression. We also found that Hsc71 is upregulated
      in response to ectopic Wnt activation, but only in the context of stem cell
      proliferation and not in head development. Hsc71's normal expression is
      consistent with a conserved role in mitosis and apoptosis inhibition. Our results
      demonstrate a hitherto unknown crosstalk between heat shock proteins and Wnt/beta
      catenin signaling. This link likely has important implications in understanding
      normal development, congenital defects and cancer biology.

PMID- 22155527
TI  - Indian hedgehog requires additional effectors besides Runx2 to induce osteoblast
      differentiation.
AB  - Indian hedgehog (Ihh) is indispensable for osteoblast differentiation during
      embryonic development of the endochondral skeleton. In the absence of Ihh, cells
      of the osteoblast lineage fail to activate the expression of Runx2, a
      transcription factor integral to osteoblast differentiation. However, it is
      hitherto unclear whether the lack of Runx2 expression is solely responsible for
      the failure of osteoblast formation in Ihh-null embryos. Here, by creating a
      mouse allele that expresses Runx2 in a Cre-dependent manner, we show that force
      expression of Runx2 in the skeletogenic cells restores bone formation in the
      Runx2-null, but not in the Ihh-null embryo. Thus, the mechanism through which Ihh
      induces osteoblast differentiation requires other effectors in addition to Runx2.

PMID- 22155528
TI  - beta band oscillations engagement in human alertness process.
AB  - We previously showed that neuronal activity in beta frequency might serve as a
      carrier for attentional arousal within the visual system of cat. In the present
      study, we adopted the animal paradigm for anticipatory attention to study
      alertness-related changes of beta activity in human subjects. The results
      indicated that increased alertness, manifested by faster responses to target
      visual stimuli, is accompanied by higher EEG activation in beta band.

PMID- 22155529
TI  - Synthesis and antiproliferative activity of some steroidal lactone compounds.
AB  - Using cholesterol as starting material, some steroidal lactone compounds with the
      structures of 3-substituted-6-oxo-7-oxa-B-homo-cholestane or 3-substituted-7-oxo
      6-oxa-B-homo-cholestane were synthesized by oxidation, reduction, Baeyer-Villiger
      reaction and condensation reaction. The cytotoxicity of these compounds against
      MGC 7901 (human gastric carcinoma), HeLa (human cervical carcinoma) and SMMC 7404
      (human liver carcinoma) cells was investigated. Our results showed that the
      synthesized compounds displayed a distinct cytotoxicity against these cancer
      cells. In particular, compounds 8 and 9 have similar cytotoxic capability as
      cisplatin does. The information obtained from the studies may be useful for the
      design of novel chemotherapeutic drugs.

PMID- 22155530
TI  - Dehydroepiandrosterone inhibits the activation and dysfunction of endothelial
      cells induced by high glucose concentration.
AB  - Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against
      diabetes; however, its mechanisms of action are unknown. Here, we focus on the
      effect of DHEA on the activation of endothelial cells induced by a high
      concentration of glucose. Adhesion on U937 cells, expression of adhesion
      molecules, production of ROS and NO, expression of eNOS, and translocation of NF
      kappaB were evaluated in human umbilical vein endothelial cells (HUVEC) treated
      with high concentrations of glucose, DHEA, or both. High concentrations of
      glucose (>20mM) induced an increase in adhesion, an increment in mainly E
      selectin and PECAM-1 expression, as well as in ROS and NO production, eNOS
      expression, translocation of NF-kappaB, and degradation of its inhibitor IkappaB
      alpha. DHEA abolished adhesion and the increase of E-selectin, ICAM-1, VCAM-1,
      and PECAM-1 induced by glucose. In addition, DHEA completely blocked oxidative
      stress and decreased translocation of NF-kappaB and the degradation of IkappaB
      alpha induced by glucose. These results suggest that DHEA protects against the
      activation of endothelial cells induced by high concentrations of glucose,
      indicating that DHEA could be useful in the treatment of hyperglycemia and
      diabetes.

PMID- 22155531
TI  - Intervening on spontaneous physical activity to prevent weight regain in older
      adults: design of a randomized, clinical trial.
AB  - There is a need to identify evidenced-based obesity treatments that are effective
      in maintaining lost weight. Weight loss results in reductions in energy
      expenditure, including spontaneous physical activity (SPA) which is defined as
      energy expenditure resulting primarily from unstructured mobility-related
      activities that occur during daily life. To date, there is little research,
      especially randomized, controlled trials, testing strategies that can be adopted
      and sustained to prevent declines in SPA that occur with weight loss. Self
      monitoring is a successful behavioral strategy to facilitate behavior change, so
      a provocative question is whether monitoring SPA-related energy expenditure would
      override these reductions in SPA, and slow weight regain. This study is a
      randomized trial in older, obese men and women designed to test the hypothesis
      that adding a self-regulatory intervention (SRI), focused around self-monitoring
      of SPA, to a weight loss intervention will result in less weight and fat mass
      regain following weight loss than a comparable intervention that lacks this self
      regulatory behavioral strategy. Participants (n=72) are randomized to a 5-month
      weight loss intervention with or without the addition of a behavioral component
      that includes an innovative approach to promoting increased SPA. Both groups then
      transition to self-selected diet and exercise behavior for a 5-month follow-up.
      Throughout the 10-month period, the SRI group is provided with an intervention
      designed to promote a SPA level that is equal to or greater than each
      individual's baseline SPA level, allowing us to isolate the effects of the SPA
      self-regulatory intervention component on weight and fat mass regain.

PMID- 22155532
TI  - Bone mineral density changes after physical training and calcium intake in
      students with attention deficit and hyper activity disorders.
AB  - In this study we investigate the effects of weight bearing exercise and calcium
      intake on bone mineral density (BMD) of students with attention deficit and hyper
      activity (ADHD) disorder. For this reason 54 male students with ADHD (age 8-12
      years old) were assigned to four groups with no differences in age, BMD, calcium
      intake, and physical activity: exercise groups with or without calcium
      supplementation (Ex+Ca+ and Ex+Ca-) and non-exercise groups with or without
      calcium supplementation (Ex-Ca+ and Ex-Ca-). The intervention involved 50 min of
      weight bearing exercise performed 3 sessions a week and/or the addition of
      dietary calcium rich food using enriched cow milk with vitamin D containing 250
      mg calcium per serving, over 9 months. Paired-samples t-test, one way ANOVA
      analysis, and Tukey tests were used to determine the main and combined effects of
      training and calcium on BMD. All groups showed greater femoral neck BMD after 9
      months. The increase in femoral neck BMD was significantly different between all
      groups (p < 0.05). Ex+Ca+ group has greater increase in BMD than other groups.
      Apparently, the effect of training was greater than calcium intake (p < 0.05).
      These results help to provide more evidence for public health organizations to
      deal with both exercise and nutrition issues in children with ADHD disorder for
      the achievement of peak BMD.

PMID- 22155533
TI  - Strengths and weaknesses in executive functioning in children with intellectual
      disability.
AB  - Children with intellectual disability (ID) were given a comprehensive range of
      executive functioning measures, which systematically varied in terms of verbal
      and non-verbal demands. Their performance was compared to the performance of
      groups matched on mental age (MA) and chronological age (CA), respectively.
      Twenty-two children were included in each group. Children with ID performed on
      par with the MA group on switching, verbal executive-loaded working memory and
      most fluency tasks, but below the MA group on inhibition, planning, and non
      verbal executive-loaded working memory. Children with ID performed below CA
      comparisons on all the executive tasks. We suggest that children with ID have a
      specific profile of executive functioning, with MA appropriate abilities to
      generate new exemplars (fluency) and to switch attention between tasks, but
      difficulties with respect to inhibiting pre-potent responses, planning, and non
      verbal executive-loaded working memory The development of different types of
      executive functioning skills may, to different degrees, be related to mental age
      and experience.

PMID- 22155534
TI  - Effects of exercise on physical fitness in children with intellectual disability.
AB  - This paper presents the results of the study which examined the effects of
      carefully designed physical exercise programs on the development of physical
      fitness in children with ID. The study sample consisted of 42 children with ID
      and 45 typically developing children. All the participants were assessed using
      Eurofit Test Battery. The results were analyzed in terms of participation in the
      exercise program and level of intellectual functioning. While ID children scored
      significantly lower on fitness tests when compared with typically developing
      children, the study revealed an association between degree of ID and physical
      fitness.

PMID- 22155535
TI  - The risk of metabolic syndrome among institutionalized adults with intellectual
      disabilities.
AB  - People with metabolic syndrome (MS) are at increased risk of coronary heart
      disease and other health problems, such as diabetes and stroke. However, there is
      little previous information on the prevalence and determinants of MS among people
      with intellectual disabilities (IDs). The present study aimed to examine the
      prevalence of MS risk factors among institutionalized adults with IDs. We
      analyzed the annual health check data of 164 institutionalized adults with IDs
      whose age was >/= 20 years in 2009. The measure of MS in the study was the
      presence of three or more of the following five components: central obesity,
      elevated blood pressure (BP), elevated fasting glucose (FG), elevated
      triglycerides (TG), and reduced high-density lipoprotein (HDL-C). The prevalence
      of MS was 11.6% in the study participants (8% in males and 17.2% in females),
      which is lower than that in the general population of Taiwan. In the logistic
      regression analysis of the occurrence of MS, we found that gender, TG and HDL-C
      were variables that could significantly predict MS after controlling for other
      potential factors. Adults with IDs who were female (OR = 38.354, 95% CI = 1.985
      741.029) and who had higher TG levels (OR = 1.043, 95% CI = 1.008-1.079) and
      reduced HDL-C levels (OR = 0.696, 95% CI = 0.549-0.883) had a statistically
      higher risk of MS. This study was one of the first to provide information on the
      prevalence of MS and its risk factors among institutionalized adults with IDs. We
      suggest that further study should focus on the specifics of MS, such as
      incidence, age-specific risk factors and further prevention or treatment in
      people with ID.

PMID- 22155536
TI  - Using an Extended Dynamic Drag-and-Drop Assistive Program to assist people with
      multiple disabilities and minimal motor control to improve computer Drag-and-Drop
      ability through a mouse wheel.
AB  - Software technology is adopted by the current research to improve the Drag-and
      Drop abilities of two people with multiple disabilities and minimal motor
      control. This goal was realized through a Dynamic Drag-and-Drop Assistive Program
      (DDnDAP) in which the complex dragging process is replaced by simply poking the
      mouse wheel and clicking. However, DDnDAP has one limitation--users cannot freely
      define their desired destinations because the program only allows for the
      dragging of targets to fixed destinations. This study evaluated whether two
      children with developmental disabilities and minimal motor control would be able
      to improve their DnD performance through an Extended Dynamic Drag-and-Drop
      Assistive Program (EDDnDAP), which improves on the aforementioned limitation of
      DDnDAP. A multiple probe design across participants was used in this study to
      assess the effects of using EDDnDAP in enhancing participants' DnD abilities.
      Participants typically received three 20-min EDDnDAP training sessions per week,
      for a period of about 6-7 weeks. Both participants significantly improved their
      DnD efficiency with the help of EDDnDAP, and both remained highly successful
      through the maintenance phase. The implications of these findings are discussed.

PMID- 22155537
TI  - The Questions About Behavioral Function (QABF): current status as a method of
      functional assessment.
AB  - Functional assessment has now entered the mainstream for evaluation and to aid in
      the treatment of challenging behaviors, while experimental functional analysis
      was at the forefront of this movement, this particular methodology has proven to
      be impractical, and thus has limited utility in real world settings. As a result
      of these factors standardized test have become a popular alternative for making a
      functional assessment. The most extensively studied of these scales to date is
      the Questions About Behavioral Function (QABF). This paper reviews the available
      research on this scale, its current status, and future directions.

PMID- 22155538
TI  - Auditory processing and speech perception in children with specific language
      impairment: relations with oral language and literacy skills.
AB  - This longitudinal study investigated temporal auditory processing (frequency
      modulation and between-channel gap detection) and speech perception (speech-in
      noise and categorical perception) in three groups of 6 years 3 months to 6 years
      8 months-old children attending grade 1: (1) children with specific language
      impairment (SLI) and literacy delay (n = 8), (2) children with SLI and normal
      literacy (n = 10) and (3) typically developing children (n = 14). Moreover, the
      relations between these auditory processing and speech perception skills and oral
      language and literacy skills in grade 1 and grade 3 were analyzed. The SLI group
      with literacy delay scored significantly lower than both other groups on speech
      perception, but not on temporal auditory processing. Both normal reading groups
      did not differ in terms of speech perception or auditory processing. Speech
      perception was significantly related to reading and spelling in grades 1 and 3
      and had a unique predictive contribution to reading growth in grade 3, even after
      controlling reading level, phonological ability, auditory processing and oral
      language skills in grade 1. These findings indicated that speech perception also
      had a unique direct impact upon reading development and not only through its
      relation with phonological awareness. Moreover, speech perception seemed to be
      more associated with the development of literacy skills and less with oral
      language ability.

PMID- 22155539
TI  - Advances in human proteomics at high scale with the SOMAscan proteomics platform.
AB  - In 1997, while still working at NeXstar Pharmaceuticals, several of us made a
      proteomic bet. We thought then, and continue to think, that proteomics offers a
      chance to identify disease-specific biomarkers and improve healthcare. However,
      interrogating proteins turned out to be a much harder problem than interrogating
      nucleic acids. Consequently, the 'omics' revolution has been fueled largely by
      genomics. High-scale proteomics promises to transform medicine with personalized
      diagnostics, prevention, and treatment. We have now reached into the human
      proteome to quantify more than 1000 proteins in any human matrix - serum, plasma,
      CSF, BAL, and also tissue extracts - with our new SOMAmer-based proteomics
      platform. The surprising and pleasant news is that we have made unbiased protein
      biomarker discovery a routine and fast exercise. The downstream implications of
      the platform are substantial.

PMID- 22155540
TI  - Comparative biochemical and functional properties of two leucine aminopeptidases
      of Clonorchis sinensis.
AB  - Leucine aminopeptidases (LAP; EC 3.4.11.1) are a group of metalloexopeptidases,
      which catalyze the sequential removal of leucine amino acids from the N-termini
      of the polypeptides or proteins. In this study, we identified two novel genes
      that encode LAPs of Clonorchis sinensis (CsLAP1 and CsLAP2) and characterized
      their biochemical and functional properties. Multiple sequence alignment of the
      deduced amino acid sequences of CsLAP1 and CsLAP2 with those of other organisms
      revealed that typical metal-binding coordinating and active site residues for
      LAPs were well conserved in CsLAP1 and CsLAP2. Recombinant CsLAP1 and CsLAP2
      showed similar biochemical properties such as pH optima at pH 8.0 and stability
      at neutral pHs. Both enzymes were specifically inhibited by bestatin and showed
      preferential substrate specificity for Leu-MCA. However, the enzymes differed in
      that they required different metal ions for maximum activity. Expressions of
      CsLAP1 and CsLAP2 were detected throughout the various developmental stages of C.
      sinensis, and their transcription levels increased gradually in accordance with
      the maturation of the parasite. Both enzymes were identified in soluble worm
      extract of C. sinensis, but not in excretory and secretory products.
      Immunolocalization studies showed that both enzymes were co-localized to the
      intestinal epithelial cells and gastrodermis of the parasite. These results
      collectively suggest that CsLAP1 and CsLAP2 are synthesized in the intestinal
      epithelial and gastrodermal cells of C. sinensis and may be involved in the final
      digestion of peptides that hydrolyzed within intestinal lumen followed by
      absorbed into gastrodermal cells of the parasite.

PMID- 22155541
TI  - Attaching the phage display-selected GLA peptide to liposomes: factors
      influencing target binding.
AB  - In our previous study, phage display selections were performed by in situ
      perfusion of a random peptide library through a mouse brain. This yielded two
      peptides (GLA and GYR) that showed significant binding to human brain endothelial
      cells (hCMEC/D3) when displayed on phage particles, but not to human umbilical
      vein endothelial cells (HUVECs). In the present study, these peptides were
      produced synthetically and coupled to liposomes to investigate the capacity of
      the peptides to act as ligands for targeting to hCMEC/D3 cells. Flow cytometry
      studies showed that these peptides when coupled to liposomes showed weak binding
      to the target brain endothelial cells. We hypothesized that the weak endothelial
      cell binding of the selected peptides when coupled to liposomes as compared to
      the binding of the peptides displayed on phage particles may be ascribed to:
      change of vehicle shape, change of peptide density, or change of peptide
      conformation. Peptide density on the liposomes influenced binding of the
      liposomes to the cells, however, this effect was minor. To study the influence of
      the peptide conformation, the GLA peptide was recombinantly produced fused to the
      N1-N2 domains of the phage p3 minor coat protein (p3-GLA) to mimic its
      conformation when displayed on phage particles. Binding of liposomes modified
      with either the GLA peptide or the p3-GLA protein to hCMEC/D3 cells was studied,
      and the p3-GLA-liposomes showed a higher binding to the cells compared to the GLA
      liposomes. The experiments demonstrate that bringing the GLA peptide into the
      original phage protein environment restores and improves the peptide binding
      capacity and suggest that the GLA peptide, with some modifications, may be used
      as a brain-targeting ligand in the future.

PMID- 22155542
TI  - Sucrose and fetal bovine serum maintain stability and activity of the budded
      baculovirus during dehydration.
AB  - Budded baculovirus has become an important vector for gene delivery, vaccine
      development, protein expression in insect and mammalian cells, and many other
      emerging applications. For high-throughput applications or for long-term storage
      and long-distance shipping, it would be useful if the infectivity and
      transduction abilities of baculovirus could be maintained at room temperature
      under dehydrated condition. The aim of this study was to design an optimized
      formula that preserves the activity of baculovirus stocks during prolonged
      periods of dehydration at various storage temperatures. The results showed that
      baculovirus without any supplement rapidly lost its transduction ability after
      dehydration. However, of many anti-oxidants, sugars, buffering agents and
      humectants tested, we found that a supplement consisting of a mixture of sucrose
      and fetal bovine serum optimally stabilized dehydrated baculovirus. This formula
      was able to maintain the dehydrated baculovirus at ~80% transduction efficiency
      after one week storage at 25 degrees C and up to 70% three weeks post
      dehydration. Thus, an optimized new formula is developed for the preservation of
      baculovirus in a dried form that can be stored for long periods at ambient
      temperatures while retaining its functional activity.

PMID- 22155543
TI  - Repeated injections of PEGylated liposomal topotecan induces accelerated blood
      clearance phenomenon in rats.
AB  - The "accelerated blood clearance (ABC) phenomenon" of PEGylated liposomes
      following multiple injections has been reported recently. This immunogenicity
      poses a problem for research into liposomes and hinders their clinical
      application. However, since doxorubicin liposomes and mitoxantrone liposomes have
      been reported to fail to induce the ABC phenomenon, some people believe that
      cytotoxic drugs loaded liposomes will not produce this ABC phenomenon under
      multiple-dosing regimens. Nevertheless, in the present study, we report that a
      first injection of the PEGylated liposomal topotecan (a cell cycle-specific drug
      for the S phase) still produced a strong ABC phenomenon. Likewise, when the first
      dose of "empty" PEGylated liposomes or topotecan liposomes was increased, the ABC
      phenomenon of the subsequent dose was accordingly attenuated. Unlike doxorubicin
      and mitoxantrone, the blood clearance rate of topotecan was dramatically rapid,
      and the hepatic and splenic accumulations of topotecan liposomes were anomalous
      because of the ABC phenomenon. These findings may present new challenges to the
      clinical application of formulations of cytotoxic drugs loaded liposomes that
      require repeated administrations.

PMID- 22155544
TI  - Paclitaxel in tyrosine-derived nanospheres as a potential anti-cancer agent: in
      vivo evaluation of toxicity and efficacy in comparison with paclitaxel in
      Cremophor.
AB  - Paclitaxel (PTX) has gained widespread clinical use yet its administration is
      associated with significant toxicity. In the present study, the toxicity and anti
      tumor efficacy of tyrosine-derived nanospheres (NSP) for the delivery of PTX was
      compared to a clinical formulation of PTX in PBS-diluted Cremophor(r) EL (PTX
      CrEL-D). Maximum tolerated dose was determined using a concentration series of
      PTX in NSP and CrEL-D, with toxicity assessed by measuring changes in body
      weight. Healthy mice administered PTX-NSP continued to gain weight normally while
      treatment with PTX-CrEL-D resulted in significant weight loss that failed to
      recover following treatment. Even at the dose of 50mg/kg, PTX-NSP showed better
      tolerance than 25mg/kg of PTX-CrEL-D. Xenograft studies of breast cancer revealed
      that the anti-tumor efficacy of PTX-NSP was equal to that of PTX-CrEL-D in tumors
      originating from both MDA-MB-435 and ZR-75-1 cancer lines. Larger volume of
      distribution and longer half-life were measured for PTX-NSP administration
      compared to those reported in the literature for a CrEL formulation. This trend
      suggests the potential for improved therapeutic index of PTX when administered
      via NSP. The findings reported here confirm that the NSP formulation is an
      efficient method for PTX administration with significant increase in maximum
      tolerated dose, offering possible clinical implications in the treatment of
      breast tumors.

PMID- 22155545
TI  - Relationships between the islets blood flow, nitric oxide, insulin, and cytosolic
      calcium in rat pancreatic islets: effects of DPP-IV inhibitor vildagliptin.
AB  - The aim of the present study was to evaluate the relationships between the islets
      blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic
      islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. For
      measuring pancreatic and islets blood a non-radioactive microsphere technique was
      used. Vehicle pre-treatment of glucose administered diabetic rats had decrease
      pancreatic and islets blood flow as compared with glucose administered normal
      rats. Blood glucose concentrations were not affected after vildagliptin
      administration in either diabetic or normal rats (10 min after glucose
      administration). Vildagliptin had no effects on baseline pancreatic or islets
      blood flow in glucose administered normal rats. Administration of vildagliptin
      increased both pancreatic and islets blood flow as compared with vehicle treated
      diabetic rats. Furthermore, diabetic rats showed significant increase in NO and
      decrease in insulin secretions and vice versa in normal rats. Vildagliptin pre
      treatment to both normal and diabetic rats had shown mild decrease in NO, but
      significantly increased insulin secretions. In addition, vildagliptin itself is
      able to mobilize intracellular Ca(2+) in pancreatic islets both in absence and
      presence of glucose. From the present study, we conclude following points (A)
      administration of vildagliptin augmented the blood flow seen in islets of
      diabetic rats, (B) islets insulin secretions are independent of islets blood flow
      and NO, (C) vildagliptin inhibited excessive NO production in diabetic rats that
      prevents the damage to beta-cells due to excessive production of peroxynitrite
      (ONOO(-)) ions and protects from cytokine-induced suppression of insulin release.

PMID- 22155546
TI  - Treatment schedule-dependent effect of 5-fluorouracil and platinum derivatives in
      colorectal cancer cells.
AB  - AIM: Combination chemotherapy for treating cancer often is superior in clinical
      efficacy to monotherapy. The aim of this study was to investigate the schedule
      dependent effect of 5-fluorouracil (5-FU) and platinum derivatives (cisplatin or
      oxaliplatin) in colorectal cancer (CRC) cell lines, and to explore factors
      affecting it. METHODS: Two human CRC-derived cell lines, DLD-1 and HCT116, were
      used. Three treatment schedules were tested, and growth inhibitory effects were
      evaluated with a WST-1 assay. Combined effects were assessed with isobolograms
      and a combination index. Cellular accumulation and DNA-binding of platinum were
      measured with inductively coupled plasma mass spectrometry. RESULTS: Exposure to
      5-FU followed by cisplatin produced synergistic effects in DLD-1 cells, and the
      amount of platinum bound to DNA was substantially increased as compared with that
      for other schedules. 5-FU and oxaliplatin also tended to be synergistic when 5-FU
      was given first, but no significant change in the cellular kinetics of platinum
      was observed. On the other hand, in HCT116 cells, the combined effects of 5-FU
      and platinum derivatives were comparable among the three schedules. CONCLUSION:
      Exposure to 5-FU followed by cisplatin had a synergistic effect in DLD-1 cells,
      suggesting that the amount of platinum bound to DNA contributes to this result.
      Also, the effect was dependent on the type of platinum derivative and cell.

PMID- 22155547
TI  - A semi-mechanistic gastric emptying pharmacokinetic model for (13)C-octanoic
      acid: an evaluation using simulation.
AB  - The aim of this paper is to assess the performance of a new mechanistic model for
      analysing (13)C-octanoic acid breath test data using simulation studies. The
      (13)C-octanoic acid breath test is widely used for indirect assessment of the
      rate of gastric emptying and it is yet to achieve universal acceptance due to
      inconsistencies when the results are compared with simultaneous and direct
      measurements using scintigraphy. The new semi-mechanistic model has five separate
      compartments; stomach, intestine, central and peripheral body and breath
      compartments. Stomach and breath profiles were simulated for 50 individuals under
      four conditions: variability on all parameters; no variability on the rate
      constant of gastric emptying and the rate constant of absorption; variability on
      the rate constant of gastric emptying and the rate constant of absorption only;
      and no variability on all parameters. A mono-exponential model was fitted to the
      stomach profile and the new semi-mechanistic model and three other widely used
      methods were fitted to the breath profiles. The gastric emptying half times from
      stomach profiles correlate better (R(2)=1,1,1,1 for the four conditions) with the
      half emptying times from the semi-mechanistic model compared with half emptying
      times from the modified exponential model (R(2)=0.72,0.53,0.88,1), Ghoos method
      (R(2)=0.72,0.54,0.88,1) and Wagner-Nelson method (R(2)=0.79,0.68,0.89,1) for the
      four simulation studies. The semi-mechanistic model is very effective for the
      assessment of GE using the (13)C-octanoic acid breath test and could be applied
      in the development of drugs that influence GE.

PMID- 22155548
TI  - Perspectives of zebrafish models of epilepsy: what, how and where next?
AB  - Epilepsy is a complex brain disorder with multiple underlying causes and poorly
      understood pathogenetic mechanisms. Animal models have been indispensable tools
      in experimental epilepsy research. Zebrafish (Danio rerio) are rapidly emerging
      as a promising model organism to study various brain disorders. Seizure-like
      behavioral and neurophysiological responses can be evoked in larval and adult
      zebrafish by various pharmacological and genetic manipulations, collectively
      emphasizing the growing utility of this model for studying epilepsy. Here, we
      discuss recent developments in using zebrafish models to study the seizure-like
      behavior involved in epilepsy, outlining current challenges and strategies for
      further translational research in this field.

PMID- 22155549
TI  - Characterization of a cellular retinol-binding protein from lamprey, Lethenteron
      japonicum.
AB  - Lampreys are ancestral representatives of vertebrates known as jawless fish. The
      Japanese lamprey, Lethenteron japonicum, is a parasitic member of the lampreys
      known to store large amounts of vitamin A within its body. How this storage is
      achieved, however, is wholly unknown. Within the body, the absorption, transfer
      and metabolism of vitamin A are regulated by a family of proteins called retinoid
      binding proteins. Here we have cloned a cDNA for cellular retinol-binding protein
      (CRBP) from the Japanese lamprey, and phylogenetic analysis suggests that lamprey
      CRBP is an ancestor of both CRBP I and II. The lamprey CRBP protein was expressed
      in bacteria and purified. Binding of the lamprey CRBP to retinol (Kd of 13.2 nM)
      was identified by fluorimetric titration. However, results obtained with the
      protein fluorescence quenching technique indicated that lamprey CRBP does not
      bind to retinal. Northern blot analysis showed that lamprey CRBP mRNA was
      ubiquitously expressed, although expression was most abundant in the intestine.
      Together, these results suggest that lamprey CRBP has an important role in
      absorbing vitamin A from the blood of host animals.

PMID- 22155550
TI  - Purification, characterization and cDNA cloning of a trypsin from the
      hepatopancreas of snakehead (Channa argus).
AB  - A trypsin was purified from the hepatopancreas of snakehead (Channa argus) by
      ammonium sulfate fractionation and a series of column chromatographies including
      DEAE-Sepharose, Sephacryl S-200 HR and Hi-Trap Capto-Q. The molecular mass of the
      purified trypsin was about 22 kDa, as estimated by SDS-PAGE. The optimum pH and
      temperature of the purified trypsin were 9.0 and 40 degrees C, respectively. The
      trypsin was stable in the pH range of 7.5-9.5 and below 45 degrees C. The
      enzymatic activity was strongly inhibited by serine proteinase inhibitors, such
      as MBTI, Pefabloc SC, PMSF, LBTI and benzamidine. Peptide mass fingerprinting
      (PMF) of the purified protein obtained 2 peptide fragments with 25 amino acid
      residues and were 100% identical to the trypsinogen from pufferfish (Takifugu
      rubripes). The activation energy (Ea) of this enzyme was 24.65 kJ.M(-1). Apparent
      K(m) was 1.02 MUM and k(cat) was 148 S(-1) for fluorogenic substrate Boc-Phe-Ser
      Arg-MCA. A trypsinogen gene encoding 247 amino acid residues was further cloned
      on the basis of the sequence obtained from PMF and the conserved site peptide of
      trypsinogen together with 5'-RACE and 3'-RACE. The deduced amino acid sequence
      contains a signal peptide of 15 residues and an activation peptide of 9 amino
      acid residues with a mature protein of 223 residues. The catalytic triad His-64,
      Asp-107, Ser-201 and 12 Cys residues which may form 6 disulfide bonds were
      conserved. Compared with the PMF data, only 2 amino acid residues difference were
      identified, suggesting the cloned trypsinogen is quite possibly the precursor of
      the purified trypsin.

PMID- 22155551
TI  - Isolation, affinity purification and biochemical characterization of a lysosomal
      cathepsin D from the deuterostome Asterias rubens.
AB  - Cathepsin D (EC 3.4.23.5) is one of the lysosomal enzymes responsible for
      proteolytic degradation in cells. By virtue of its mannose 6-phosphate residues,
      shortly after its synthesis, it is recognized by the receptors in the trans-Golgi
      network that mediate its transport to the lysosomes. The mammalian enzyme has
      been extensively characterized and several forms of cathepsin have also been
      identified. Cathepsins have also been isolated from other vertebrates and
      invertebrates and recent studies suggest that the lysosomal sorting machinery is
      evolutionarily conserved from fish to mammals. We recently characterized the
      putative mannose 6-phosphate receptors from the invertebrate starfish (Asterias
      rubens). In the present study we affinity purified the cathepsin D from this
      animal and biochemically characterized the same. Purified enzyme migrated as a
      single band on SDS-PAGE corresponding to a molecular mass of 45 kDa. The protein
      bound specifically to Con A-Sepharose gel and is glycosylated. The deglycosylated
      enzyme showed a molecular mass of ~40 kDa. Furthermore, an antibody raised for
      the purified enzyme in a rabbit recognizes the crude, the purified enzyme as well
      as the deglycosylated product in a western blot experiment. The enzyme in the
      extracts of different tissues can also be quantified by ELISA. We have further
      evaluated the binding of purified starfish cathepsin D with its receptor, MPR 300
      (mannose 6-phosphate receptor) by immunoprecipitation. Cross-linking experiments
      using purified cathepsin D and MPR 300 revealed a cross-linked product that
      migrated with a higher molecular mass (345 kDa) compared to the enzyme (45 kDa).
      Furthermore the specificity of this interaction was also tested in a ligand blot
      experiment.

PMID- 22155552
TI  - Nucleotide allosteric regulation of the glutamate dehydrogenases of Teladorsagia
      circumcincta and Haemonchus contortus.
AB  - The expression of glutamate dehydrogenase (GDH; EC 1.4.1.3) in L3 of the nematode
      Haemonchus contortus was confirmed by detecting GDH mRNA, contrary to earlier
      reports. The enzyme was active in both L3 and adult H. contortus homogenates
      either with NAD(+)/H or NADP(+)/H as co-factor. Although it was a dual co-factor
      GDH, activity was greater with NAD(+)/H than with NADP(+)/H. The rate of the
      aminating reaction (glutamate formation) was approximately three times higher
      than for the deaminating reaction (glutamate utilisation). GDH provides a pathway
      for ammonia assimilation, although the affinity for ammonia was low. Allosteric
      regulation by GTP, ATP and ADP of L3 and adult H. contortus and Teladorsagia
      circumcincta (Nematoda) GDH depended on the concentration of the regulators and
      the direction of the reaction. The effects of each nucleotide were qualitatively
      similar on the mammalian and parasite GDH, although the nematode enzymes were
      more responsive to activation by ADP and ATP and less inhibited by GTP under
      optimum assay condition. GTP inhibited deamination and low concentrations of ADP
      and ATP stimulated weakly. In the reverse direction, GTP was strongly inhibitory
      and ADP and ATP activated the enzyme.

PMID- 22155553
TI  - Alkane-modified short polyethyleneimine for siRNA delivery.
AB  - RNA interference (RNAi) is a highly specific gene-silencing mechanism triggered
      by small interfering RNA (siRNA). Effective intracellular delivery requires the
      development of potent siRNA carriers. Here, we describe the synthesis and
      screening of a series of siRNA delivery materials. Short polyethyleneimine (PEI,
      Mw 600) was selected as a cationic backbone to which lipid tails were conjugated
      at various levels of saturation. In solution these polymer-lipid hybrids self
      assemble to form nanoparticles capable of complexing siRNA. The complexes silence
      genes specifically and with low cytotoxicity. The efficiency of gene knockdown
      increased as the number of lipid tails conjugated to the PEI backbone increased.
      This is explained by reducing the binding affinity between the siRNA strands to
      the complex, thereby enabling siRNA release after cellular internalization. These
      results highlight the importance of complexation strength when designing siRNA
      delivery materials.

PMID- 22155554
TI  - Clinical impact of serum proteins on drug delivery.
AB  - Among serum proteins albumin and transferrin have attracted the most interest as
      drug carriers in the past two decades. Prior to that, their potential use was
      overshadowed by the advent of monoclonal antibodies that was initiated by
      Milstein and Koehler in 1975. Meanwhile intensive pursuit of exploiting
      transferrin, but above all albumin as an exogenous or endogenous carrier protein
      for treating various diseases, primarily cancer, rheumatoid arthritis, diabetes
      and hepatitis has resulted in several marketed products and numerous clinical
      trials. While the use of transferrin has clinically been primarily restricted to
      immunotoxins, albumin-based drug delivery systems ranging from albumin drug
      nanoparticles, albumin fusion protein, prodrugs and peptide derivatives that bind
      covalently to albumin as well as physically binding antibody fragments and
      therapeutically active peptides are in advanced clinical trials or approved
      products. For treating diabetes, Levemir and Victoza that are myristic acid
      derivatives of human insulin or glucagon-like peptide 1 (GLP-1) act as long
      acting peptides by binding to the fatty acid binding sites on circulating albumin
      to control glucose levels. Levemir from Novo Nordisk has already developed into a
      blockbuster since its market approval in 2004. Abraxane, an albumin paclitaxel
      nanoparticle as a water-soluble galenic formulation avoiding the use of
      cremophor/ethanol, transports paclitaxel through passive targeting as an albumin
      paclitaxel complex to the tumor site and is superior to conventional Taxol
      against metastatic breast cancer. INNO-206, an albumin-binding doxorubicin
      prodrug that also accumulates in solid tumors due to the enhanced permeability
      and retention (EPR) effect but releases the parent drug through acid cleavage,
      either intra- or extracellularly, is entering phase II studies against sarcoma.
      An expanding field is the use of albumin-binding antibody moieties which do not
      contain the fragment crystallizable (Fc) portion of, conventional immunoglobulin
      G (IgG) but are comprised of monovalent or bivalent light and/or heavy chains and
      incorporate an additional albumin-binding peptide or antibody domain. The most
      advanced antibody of this kind is ATN-103 (Ozoralizumab), a trivalent albumin
      binding nanobody that neutralizes the pro-inflammatory tumor necrosis factor
      alpha (TNF-alpha) as a causative agent for exacerbating rheumatoid arthritis. ATN
      103 is currently in multi-center phase II trials against this debilitating
      disease. In summary, because albumin as the most abundant circulating protein
      cannot only be used to improve the pharmacokinetic profile of therapeutically
      relevant peptides and the targeting moiety of antibodies but also for peptide
      based targeting as well as low-molecular weight drugs to inflamed or malignant
      tissue, it is anticipated that R&D efforts of academia and the pharmaceutical
      industry in this field of drug delivery will prosper.

PMID- 22155555
TI  - Development of self-immolative dendrimers for drug delivery and sensing.
AB  - Traditional dendrimers possess unique cascade-branched structural properties that
      allow for multivalent modifications with drug cargos, targeting/delivery agents
      and imaging tools. In addition to multivalency, the dendrimer's macromolecular
      size also brings about the enhanced permeability and retention (EPR) effect,
      which makes it an attracting agent for drug delivery and biosensing. Similar to
      other macromolecules, therapeutic application of dendrimers in the human body
      faces practical challenges such as target specificity and toxicity. The latter
      represents a substantial issue due to the dendrimer's unnatural chemical
      structure and relatively large size, which prohibit its in vivo degradation and
      excretion from the body. To date, a class of self-immolative dendrimers has been
      developed to overcome these obstacles, which takes advantage of its unique
      structural backbone to allow for cascade decompositions upon a simple triggering
      event. The specific drug release can be achieved through a careful design of the
      trigger, and as a result of the fragmentation, the generated small molecules are
      either biodegradable or easily excreted from the body. Though still at a
      preliminary stage, the development of this novel approach represents an important
      direction in nanoparticle-mediated drug delivery and sensor design, thereby
      opening up an insightful frontier of dendrimer based applications.

PMID- 22155556
TI  - Determinants of serum alpha-fetoprotein levels in hepatitis C-infected patients.
AB  - BACKGROUND & AIMS: Little information is available about what factors determine
      serum levels of alpha fetoprotein (AFP) (eg, demographic, virologic, or clinical
      features) among individuals who do not develop hepatocellular carcinoma (HCC).
      This information might improve AFP-based algorithms for HCC detection. METHODS:
      We examined data from patients in the national Veterans' Affairs Hepatitis C
      Virus (HCV) Clinical Case Registry who received at least 1 AFP test (258,275 AFP
      tests in 76,357 patients; 1.9% developed HCC). We constructed hierarchical
      multivariate models of AFP levels. Potential predictors of AFP values included
      patients' sex, race, cirrhosis status, Model for End-Stage Liver Disease (MELD)
      score, HCV genotype, level of alanine aminotransferase (ALT) within 30 days
      before the AFP test, time to diagnosis of HCC, and time elapsed from the HCV
      index date. RESULTS: Significant determinants for increased levels of AFP
      included presence of cirrhosis, higher MELD scores, and increased levels of ALT.
      AFP levels were also affected by the interaction between ALT levels and the
      presence and time to development of HCC. Among patients who did not have HCC, the
      AFP level increased with the level of ALT; the AFP values in the presence of ALT
      37-56 U/L, ALT 57-92 U/L, or ALT >92 U/L were 16%, 35%, and 68% higher,
      respectively, than AFP values at ALT 0-36 U/L. However, patients who developed
      HCC within 30 days of receiving the AFP test had a lower rate of increase in AFP
      with each higher category of ALT level, with increases of 31%, 39%, and 37% for
      the same respective ALT categories. CONCLUSIONS: In patients with chronic HCV
      infection, AFP and ALT values correlate; however, among patients with HCC, levels
      of AFP increase disproportionately to or unaccompanied by increases in levels of
      ALT. The prognostic and diagnostic value of AFP levels might be increased by
      adjusting for ALT values.

PMID- 22155557
TI  - Increased rate of spontaneous bacterial peritonitis among cirrhotic patients
      receiving pharmacologic acid suppression.
AB  - BACKGROUND & AIMS: Patients with cirrhosis frequently receive proton pump
      inhibitor (PPI) or H2-receptor antagonist therapies. We investigated whether acid
      suppressive therapy is associated with spontaneous bacterial peritonitis (SBP) in
      cirrhotic patients with ascites. METHODS: We compared data from 65 hospitalized
      cirrhotic patients with paracentesis-proven SBP, collected from 2006 to 2009,
      with those of 65 contemporaneous, hospitalized cirrhotic patients without SBP
      (controls). We evaluated PPI use and analyzed the effects of covariates. RESULTS:
      Patients with SBP had a significantly higher incidence of recent (past 7 days)
      PPI use (71%) than controls (42%). Of patients with SBP, 68% had no documented
      indication for PPI therapy. Based on multivariable logistic regression analysis,
      subjects who had not taken PPIs in the past 90 days were almost 70% less likely
      to develop SBP than those who had taken PPIs in the previous 7 days. Subjects who
      took PPIs within 8 to 90 days before hospitalization were 79% less likely to
      develop SBP than those who took PPIs within 7 days before hospitalization. There
      was no significant difference between patients who received no PPI therapy in the
      previous 90 days versus those who had taken PPIs in the previous 8 to 90 days (P
      = .58). Hyponatremia was associated significantly with SBP. There were no
      significant differences in length of hospital stay or 30-day survival for the SBP
      and control groups. CONCLUSIONS: Pharmacologic acid suppression is associated
      with SBP in patients with advanced cirrhosis. Prospective studies are needed to
      determine the mechanism of this association and to determine whether reduced use
      of PPIs and H2-receptor antagonists reduce the incidence of SBP.

PMID- 22155558
TI  - Impact of the 2008-2009 economic recession on screening colonoscopy utilization
      among the insured.
AB  - BACKGROUND & AIMS: Economic factors might affect the use of recommended
      preventative services. We sought to determine whether the recent severe economic
      recession was associated with diminished screening colonoscopy rates among an
      insured population and to assess the relationship between out-of-pocket (OOP)
      costs and screening colonoscopy use. METHODS: Administrative data from 106 health
      plans (IMS LifeLink Health Plan Claims Database) were analyzed to determine
      monthly rates of screening colonoscopies performed on beneficiaries ages 50 to 64
      years between January 2005 and November 2007 (prerecession), as well as from
      December 2007 through June 2009 (recession). Segmented regression models were
      used to evaluate changes in screening colonoscopy rates, as well as the
      relationship between screening and OOP costs before and during the recession.
      RESULTS: Compared with prerecession trends, during the recession screening
      colonoscopy rates decreased by 68.9 colonoscopies/1 million individuals per month
      (95% confidence interval, -84.6 to -53.1; P < .001). Application of study
      estimates to the entire US population indicated that during the recession,
      commercially insured patients aged 50 to 64 years underwent approximately 500,000
      fewer screening colonoscopies. Compared with those with low OOP costs, those with
      high OOP procedure costs had lower rates of screening before and during the
      recession, and had a greater reduction in screening rates during the recession (P
      = .035). CONCLUSIONS: During the recession of December 2007 to June 2009, insured
      individuals reduced their use of screening colonoscopy compared with the 2 years
      before the recession began. OOP costs were related inversely to screening use,
      especially during the recession. Policies to reduce cost sharing could increase
      adherence to recommended preventive services such as colonoscopy examinations.

PMID- 22155559
TI  - Awareness of surveillance recommendations among patients with colorectal
      adenomas.
AB  - BACKGROUND & AIMS: The efficacy of colorectal cancer screening programs depends
      on the rate of attendance at surveillance colonoscopy examinations. Increasing
      patients' awareness about the importance of surveillance might improve
      attendance, but it is not clear how much they know about their follow-up
      recommendations. We assessed the awareness of patients with adenomas about their
      surveillance recommendations. METHODS: Ten endoscopy departments provided access
      to their colonoscopy database for quality assurance; 2 datasets were obtained. We
      analyzed data from 4000 colonoscopies (400 per department) performed on patients
      with adenomas. All the patients were mailed a survey to determine how much
      information they had about their colonoscopy results and their follow-up
      recommendations. Data from 549 patients were included in the analysis. We also
      assessed surveillance attendance among 500 patients (50 per department) who had
      adenomas removed. RESULTS: Of the patients analyzed, 85% recalled retrieval of
      polyps during their colonoscopy, and 85% recalled whether they needed
      surveillance or not. The indication for surveillance was recalled by 69% of
      patients (range between departments, 55%-83%; P < .01). Factors that were
      associated with awareness of recommendations were younger age (odds ratio [OR],
      1.06; 95% confidence interval [CI], 1.06-1.09), treatment by a gastroenterologist
      (OR, 5.53; 95% CI, 3.28-9.32), and presence of 3 or more adenomas (OR, 2.97; 95%
      CI, 1.29-6.85). Attendance among patients with adenomas varied among departments,
      from 60% to 89% (P < .01), and was not associated with awareness of patients
      about their recommendations per department (P = .59). CONCLUSIONS: Not enough
      patients (only 85%) who receive colonoscopies are aware of their results or
      surveillance recommendations. Although awareness of findings and recommendations
      did not correlate with follow-up attendance, patients should be better informed
      about findings and their need for surveillance.

PMID- 22155560
TI  - Reduced cortical thickness of brain areas involved in pain processing in patients
      with chronic pancreatitis.
AB  - BACKGROUND & AIMS: Patients with painful chronic pancreatitis (CP) might have
      abnormal brain function. We assessed cortical thickness in brain areas involved
      in visceral pain processing. METHODS: We analyzed brain morphologies of 19
      patients with painful CP and compared them with 15 healthy individuals (controls)
      by using a 3T magnetic resonance scanner. By using an automated method with
      surface-based cortical segmentation, we assessed cortical thickness of the
      primary (SI) and secondary (SII) somatosensory cortex; prefrontal cortex (PFC);
      frontal cortex (FC); anterior (ACC), mid (MCC), and posterior (PCC) cingulate
      cortex; and insula. The occipital middle sulcus was used as a control area. The
      pain score was determined on the basis of the average daily amount of pain during
      1 week. RESULTS: Compared with controls, patients with CP had reduced overall
      cortical thickness (P = .0012), without effects of modification for diabetes,
      alcoholic etiologies, or opioid treatment (all P values >.05). In patients with
      CP, the cortical thickness was decreased in SII (P = .002, compared with
      controls), PFC (P = .046), FC (P = .0003), MCC (P = .001), and insula (P = .002).
      There were no differences in cortical thickness between CP patients and controls
      in the control area (P = .20), SI (P = .06), ACC (P = .95), or PCC (P = .42).
      Cortical thickness in the affected areas correlated with pain score (r = 0.47, P
      = .003). CONCLUSIONS: In patients with CP, brain areas involved in pain
      processing have reduced cortical thickness. As a result of long-term, ongoing
      pain input to the neuromatrix, cortical thickness might serve as a measure for
      overall pain system dysfunction, as observed in other diseases characterized by
      chronic pain.

PMID- 22155561
TI  - Maintenance of heartburn relief after step-down from twice-daily proton pump
      inhibitor to once-daily dexlansoprazole modified release.
AB  - BACKGROUND & AIMS: Many patients with gastroesophageal reflux disease (GERD) take
      a proton pump inhibitor (PPI) twice daily to control symptoms. Once-daily
      dexlansoprazole modified release (MR) has a dual-delayed release formulation,
      making it attractive for step-down management of patients whose symptoms are well
      controlled on twice-daily PPIs. We investigated whether step-down to once-daily
      dexlansoprazole controls heartburn in patients with GERD who were receiving twice
      daily PPI therapy. METHODS: Patients 18 years and older taking a twice-daily PPI
      for symptom control were enrolled (n = 178) in a single-blind, multicenter study;
      163 patients completed the study and 142 patients met criteria for the efficacy
      analysis. During the 6-week screening and treatment periods, patients recorded
      the presence of heartburn symptoms twice daily in electronic diaries. Patients'
      heartburn was considered well controlled if they had an average of 1 symptom or
      fewer per week during the last 4 weeks of screening and treatment. After
      screening, qualified patients were switched to masked dexlansoprazole MR 30 mg
      and placebo for 6 weeks. The primary efficacy end point was the proportion of
      patients whose heartburn remained well controlled after step-down. GERD-related
      symptoms and quality of life (QOL) also were evaluated using the Patient
      Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM)
      and the PAGI-QOL questionnaires, respectively. RESULTS: After step-down to once
      daily dexlansoprazole MR 30 mg, heartburn remained well controlled in 88% of
      patients (125 of 142). These patients were able to maintain their GERD-related
      symptom severity and QOL, indicated by marginal changes in the PAGI-SYM and PAGI
      QOL total and subscale scores, respectively. CONCLUSIONS: Most patients with GERD
      who take twice-daily PPI to control heartburn are able to successfully step down
      to once-daily dexlansoprazole 30 mg.

PMID- 22155562
TI  - Similar outcomes of surgical and medical treatment of intra-abdominal abscesses
      in patients with Crohn's disease.
AB  - BACKGROUND & AIMS: It is not clear whether medical therapy, surgery, or both is
      the best approach for patients with Crohn's disease who develop an intra
      abdominal abscess. METHODS: We evaluated data from patients with Crohn's disease
      who were diagnosed with a radiologically confirmed abdominal abscess (enhancing
      fluid collection, >= 1 cm) from 1999 to 2006 (n = 95; median age, 42.0 y; 50.5%
      female). Medical/nonsurgical methods (percutaneous aspiration +/- drain
      placement) were used for 55 patients (mean abscess size, 6.9 +/- 3.2 cm), and 40
      patients underwent surgical interventions (laparotomy +/- bowel resection; mean
      abscess size, 7.5 +/- 3.7 cm). We investigated risk factors for abscess
      recurrence. RESULTS: The median length of hospitalization was 15.5 days for
      patients who underwent surgery and 5.0 days for patients who did not (P < .001).
      The 5-year cumulative probability of abscess recurrence was 31.2% among patients
      who did not undergo surgery and 20.3% among those who did (P = .25). Histories of
      perianal or active ileal disease predicted abscess recurrence. Initiation of
      pharmacologic therapy after drainage reduced the risk for abscess recurrence (P <
      .001). Anti-tumor necrosis factor therapy, compared with no therapy, reduced the
      risk of abscess recurrence (P = .001) in all patients, whereas immunosuppressive
      monotherapy, compared with no therapy, had a trend toward significant risk
      reduction (P = .06). CONCLUSIONS: Among patients with Crohn's disease who have
      intra-abdominal abscesses, nonsurgical and primary surgical management strategies
      result in similar rates of abscess recurrence and complications. Initiation of
      anti-tumor necrosis factor and/or immunosuppressive therapy when abscesses
      resolve might protect against intra-abdominal penetrating disease.

PMID- 22155563
TI  - Global enhancement of nuclear localization-dependent nuclear transport in
      transformed cells.
AB  - Fundamental to eukaryotic cell function, nucleocytoplasmic transport can be
      regulated at many levels, including through modulation of the importin/exportin
      (Imp/Exp) nuclear transport machinery itself. Although Imps/Exps are
      overexpressed in a number of transformed cell lines and patient tumor tissues,
      the efficiency of nucleocytoplasmic transport in transformed cell types compared
      with nontransformed cells has not been investigated. Here we use quantitative
      live cell imaging of 3 isogenic nontransformed/transformed cell pairs to show
      that nuclear accumulation of nuclear localization signal (NLS)-containing
      proteins, but not their NLS-mutated derivatives, is increased up to 7-fold in
      MCF10CA1h human epithelial breast carcinoma cells and in simian virus 40 (SV40)
      transformed fibroblasts of human and monkey origin, compared with their
      nontransformed counterparts. The basis for this appears to be a significantly
      faster rate of nuclear import in transformed cell types, as revealed by analysis
      using fluorescence recovery after photobleaching for the human MCF10A/MCF10CA1h
      cell pair. Nuclear accumulation of NLS/nuclear export signal-containing
      (shuttling) proteins was also enhanced in transformed cell types, experiments
      using the nuclear export inhibitor leptomycin B demonstrating that efficient Exp
      1-mediated nuclear export was not impaired in transformed compared with
      nontransformed cells. Enhanced nuclear import and export efficiencies were found
      to correlate with 2- to 4-fold higher expression of specific Imps/Exps in
      transformed cells, as indicated by quantitative Western blot analysis, with
      ectopic expression of Imps able to enhance NLS nuclear accumulation levels up to
      5-fold in nontransformed MCF10A cells. The findings indicate that transformed
      cells possess altered nuclear transport properties, most likely due to the
      overexpression of Imps/Exps. The findings have important implications for the
      development of tumor-specific drug nanocarriers in anticancer therapy.

PMID- 22155564
TI  - Normal role of the low-molecular-weight neurofilament protein in mitochondrial
      dynamics and disruption in Charcot-Marie-Tooth disease.
AB  - Intermediate filaments serve important structural roles, but other cellular
      functions are increasingly recognized. This study demonstrated normal function of
      the low-molecular-weight neurofilament protein (NFL) in mitochondrial dynamics
      and disruption in Charcot-Marie-Tooth disease (CMT) due to mutations in the Nefl
      gene. In motor neurons of spinal cord cultured from Nefl-knockout mice,
      mitochondrial length and the rate of fusion were decreased concomitant with
      increased motility. These parameters were normalized after expression of NFL(wt)
      on the Nefl(-/-) background, but not by overexpression of the profusion protein,
      mitofusin 2 (MFN2). The effects of CMT-causing NFL mutants bore similarities to
      and differences from Nefl knockout. In the early phase of toxicity before
      disruption of the neurofilament network, NFL(Q333P) and NFL(P8R) integrated into
      neurofilaments and had effects on mitochondria similar to those with Nefl
      knockout. The reduction of fusion rate by NFL(Q333P) was partly due to
      interference with the function of the profusion protein MFN2, which is mutated in
      CMT2A, functionally linking these forms of CMT. In the later phase of toxicity,
      mitochondria essentially stopped moving in neurons expressing NFL mutants,
      probably a consequence of cytoskeletal disruption. Overall, the data point to
      important functions of neurofilaments in mitochondrial dynamics as well as
      primary involvement in CMT2E/1F.

PMID- 22155565
TI  - Epithelial progesterone receptor exhibits pleiotropic roles in uterine
      development and function.
AB  - The ovarian steroid progesterone, acting through the progesterone receptor (PR),
      coordinates endometrial epithelial-stromal cell communication, which is critical
      for its development and function. PR expression in these cellular compartments is
      under tight temporal and endocrine control. Although ex vivo studies demonstrated
      the importance of stromal PR expression, they failed to show a role for
      epithelial PR in uterine function. Here, the in vivo role of PR in the uterine
      epithelium is defined using floxed PR (PR(f/f)) mice crossed to Wnt7a-Cre mice.
      Progesterone was unable to stimulate the expression of its epithelial target
      genes, including Ihh, in the Wnt7a-Cre(+)PR(f/-) mice. Analysis was conducted on
      Ihh to determine whether PR directly regulates epithelial gene transcription.
      ChIP-on-chip analysis identified PR binding sites in the 5'-flanking region of
      Ihh. Cotransfection of the proximal Ihh promoter with PR demonstrated that PR
      directly regulates Ihh transcription. Female Wnt7a-Cre(+)PR(f/-) mice are
      infertile due to defects in embryo attachment, stromal cell decidualization, and
      the inability to cease estrogen-induced epithelial cell proliferation. Finally,
      progesterone was unable to inhibit neonatal endometrial glandular development in
      Wnt7a-Cre(+)PR(f/-) mice. Thus, epithelial PR is necessary for the regulation of
      progesterone epithelial target gene expression, as well as uterine function and
      development.

PMID- 22155566
TI  - Aldosterone and mineralocorticoid receptors: a personal reflection.
AB  - Since the isolation and characterization of aldosterone in 1953, subsequent
      developments in the field can be neatly considered over three time spans, each of
      two decades. In the first aldosterone itself was the primary focus; from 1973,
      for two decades the mineralocorticoid receptor (MR) was the front runner; since
      1993 the focus has been on both, with aldosterone being discovered by
      cardiologists, and distinguished within their panoply of neurohumoral factors.

PMID- 22155567
TI  - Seasonal effect of GnIH on gonadotrope functions in the pituitary of goldfish.
AB  - Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin release in birds and
      mammals. To investigate its role in teleosts, we examined the effects of
      synthetic goldfish (g)GnIH on pituitary LH-beta and FSH-beta subunit, and gGnIH
      receptor (gGnIH-R) mRNA levels and LH secretion in goldfish. Intraperitoneal
      injections of gGnIH increased pituitary LH-beta and FSH-beta mRNA levels at early
      to late gonadal recrudescence, but reduced serum LH and pituitary gGnIH-R mRNA
      levels, respectively, at early to mid-recrudescence and later stages of
      recrudescence. Static incubation with gGnIH elevated LH secretion from dispersed
      pituitary cell cultures from prespawning fish, but not at other recrudescent
      stages; suppressed LH-beta mRNA levels at early recrudescence and prespawning but
      elevated LH-beta at mid-recrudescence; and consistently attenuated FSH-beta mRNA
      in a dose-specific manner. Results indicate that in goldfish, regulation of LH
      secretion and gonadotropin subunit mRNA levels are dissociated in the presence of
      gGnIH and dependent on maturational status and administration route.

PMID- 22155568
TI  - Luteinizing hormone (LH) regulates production of androstenedione and progesterone
      via control of histone acetylation of StAR and CYP17 promoters in ovarian theca
      cells.
AB  - Although luteinizing hormone (LH) affects androstenedione (A4) and progesterone
      (P4) production in theca cells, it is still unknown how LH influences molecular
      mechanism of A4 and P4 production. To examine the relationship between LH and
      transcription factors involved in A4 and P4 production, ovarian theca cells were
      cultured in the presence or absence of high concentrations of LH for 24 h (pre
      treatment with high concentration of LH) and then cultured in the presence or
      absence of low concentration of LH for 48 h. Low LH enhanced production of A4 and
      P4, and expressions of CYP17 and StAR mRNA in theca cells without pre-treatment
      with high LH. In addition, low LH stimulated the expression of SF-1 protein in
      nuclear fractions from theca cells with or without pre-treatment with high LH.
      The binding of SF-1 to the CYP17 and StAR promoter regions increased in theca
      cells treated with low LH. Although GATA-4 and GATA-6 are both found in the
      nuclear fraction but not in the cytosol of theca cells, low LH enhanced the
      binding of GATA-6, but not of GATA-4, to the CYP17 promoter region without pre
      treatment with high LH. Acetylation histone H3 in StAR and CYP17 promoter regions
      were changed by different LH-dosage. Overall, we showed that LH regulates the
      production of A4 and P4 by affecting the nuclear localization and switching of
      transcription factors in theca cells and that target transcription factors
      involved in steroid production in theca cells are changed by different LH
      concentration.

PMID- 22155569
TI  - Histone H2B ubiquitin ligases RNF20 and RNF40 in androgen signaling and prostate
      cancer cell growth.
AB  - Since data-mining from the Oncomine database revealed that expression of histone
      H2B K120 monoubiquitin (H2Bub1) ligase RNF20 is decreased in metastatic prostate
      cancer, we elucidated the effect of RNF20 and its homolog RNF40 on androgen
      receptor (AR)-dependent transcription and prostate cancer cell growth. Both RNF20
      and RNF40 were able to functionally and physically interact with the AR and
      modulate its transcriptional activity in intact cells. Chromatin
      immunoprecipitation analyses showed that the androgen induction of FKBP51 and PSA
      in LNCaP prostate cancer cells is accompanied with a dynamic increase in the
      H2Bub1 within the transcribed regions of these loci. Interestingly, depletion of
      RNF20 or RNF40 strongly retarded the growth of LNCaP cells, which was however
      unlikely to be due to altered androgen signaling, but due to decreased expression
      of several cell cycle promoters. Collectively, our results suggest that RNF20 and
      RNF40, either via ubiquitylation of H2B or other targets, are coupled to the
      proliferation of prostate cancer cells.

PMID- 22155570
TI  - Diatomaceous earth and oil enhance effectiveness of Metarhizium anisopliae
      against Triatoma infestans.
AB  - Entomopathogenic fungi, especially Metarhizium anisopliae, have potential for
      integrated control of peridomestic triatomine bugs. However, the high
      susceptibility of these vectors to fungal infection at elevated ambient
      humidities decreases in the comparatively dry conditions that often prevail in
      their microhabitats. A formulation adapted to this target pest that induces high
      and quick mortality can help to overcome these drawbacks. In the present study
      diatomaceous earth, which is used against pests of stored grains or as an
      additive to mycoinsecticides, delayed but did not reduce in vitro germination of
      M. anisopliae s.l. IP 46 conidia after >24h agitation without affecting
      viability, and did not hamper the survival of Triatoma infestans nymphs exposed
      to treated surfaces. The settling behavior of nymphs on a treated surface in
      choice tests depended on the concentration of diatomaceous earth and ambient
      light level. Conidia formulated with diatomaceous earth and a vegetable oil
      synergized the insecticidal effect of the fungus in nymphs, and quickly killed
      all treated insects, even at 75% relative humidity (LT(90) 8.3 days) where
      unformulated conidia caused only 25% mortality after a 25 days exposure. The
      improved performance of a combined oil and desiccant dust formulation of this
      Metarhizium isolate raises the likelihood for its successful mycoinsecticidal use
      for triatomine control and, apparently, against other domestic insect pests.

PMID- 22155571
TI  - Improvement of the green fluorescent protein reporter system in Leishmania spp.
      for the in vitro and in vivo screening of antileishmanial drugs.
AB  - Development of new therapeutic approaches for leishmaniasis treatment requires
      new high throughput screening methodologies for the antileishmanial activity of
      the new compounds both in vitro and in vivo. Reporter genes as the GFP have
      become one of the most promissory and widely used tools for drug screening in
      several models, since it offers live imaging, high sensibility, specificity and
      flexibility; additionally, the use of GFP as a reporter gene in screening assays
      eliminates all the drawbacks presented in conventional assays and also those
      technical problems found using other reporter genes. The utility of the GFP as a
      reporter gene in drug screening assays with Leishmania parasites depends on the
      homogeneity and stability of the GFP transfected strains. Stable expression of
      the GFP in the Old World Leishmania species has been demonstrated using
      integration vectors; however, no reports exist yet about the success of this
      methodology in the New World species. Here we report the generation of New World
      Leishmania strains expressing the GFP protein from an integration vector, which
      replaces one copy of the 18S RNA in the chromosome with the GFP coding sequence
      by homologous recombination. We also prove that the expression of the integrated
      GFP is stable and homogeneous in the transfected parasites after months in
      culture without selective pressure or during its use in hamster infection assays.
      The fluorescent strains are useful for in vitro, ex vivo and in vivo drug
      screening assays since no considerable variations in virulence or infectivity
      where seen attributable to the genetic manipulation during both in vitro and in
      vivo infection experiments. The platform described here for drug testing assays
      based on the use of stable fluorescent Leishmania strains coupled to flow
      cytometry and fluorescent microscopy is more sensitive, more specific and faster
      than conventional assays used normally for the evaluation of compounds with
      potential antileishmanial activity.

PMID- 22155572
TI  - Delving into foot mechanics and related problems.
AB  - Foot problems are common in elders, stemming from age-related podiatric
      mechanical problems or disease-induced pathology. Common mechanical problems
      include hammertoe, arthritis, bunions, and metatarsalgia. Disease-induced
      conditions include onychomycosis, athlete's foot, plantar warts, gout, and
      diabetes. Treatment is case-specific and often involves multiple interventions,
      including lifestyle changes. Prevention and treatment strategies are presented.
      Patient education on proper foot care is effective.When patients are unable to
      reach or see their feet, staff assumes responsibility for foot care.

PMID- 22155573
TI  - Entrepreneurs: leading the way to pharmacy's future.
AB  - Entrepreneurship has always been central to the practice of pharmacy. Whether
      opening a new retail store, setting up a unique clinic practice, or researching a
      novel therapy, pharmacists are continually looking forward and following their
      visions of how pharmacy can be part of a new direction in health care. In 2011,
      the American Society of Consultant Pharmacists (ASCP) Foundation--itself the
      product of entrepreneurship--awarded grants to three entrepreneurs who are
      seeking to establish a fee-for-service component of their senior care pharmacy
      practices in the community. The grant recipients, while differing in their
      approaches, share the common goal of providing safe, effective, and cost
      justified medication therapy and education to ambulatory older adults.

PMID- 22155574
TI  - Use of potentially inappropriate medications in an ambulatory Medicare
      population.
AB  - OBJECTIVE: To determine the prevalence of potentially inappropriate medication
      (PIM) use by applying the Beers criteria in an ambulatory population of Medicare
      beneficiaries, and to identify the most common PIMs/PIM classes taken by this
      population. DESIGN: Cross-sectional, observational study. SETTING: Nine community
      outreach events throughout central and northern California. PATIENTS: 295
      ambulatory Medicare beneficiaries (65 to 98 years of age). INTERVENTIONS:
      Pharmacy students, under the supervision of licensed pharmacists, assisted
      beneficiaries with Medicare Part D plan enrollment and medication review,
      including identification of PIMs. MAIN OUTCOME MEASURES: Number of PIMs taken by
      beneficiaries and the most frequent PIMs/PIM classes. RESULTS: 54 (18.3%)
      beneficiaries were taking at least one PIM. The most common PIMs taken by the
      study group were alprazolam, clonidine, and estrogen. The two most common classes
      of such medications were benzodiazepines and antiarrhythmics. CONCLUSION: Many
      older adults continue to receive medications that should be avoided because of
      limited effectiveness and/or potential for harm. Prescribers and pharmacists must
      be diligent in ensuring that medications given to older adults are necessary and
      appropriate. Outreach events targeting seniors provide an ideal forum to identify
      and address such issues.

PMID- 22155575
TI  - Risperidone for post-traumatic combat nightmares: a report of four cases.
AB  - OBJECTIVE: To report the response to low-dose risperidone in individuals with
      combat-related post-traumatic stress disorder (PTSD) combat nightmares. DESIGN:
      Case series. SETTING: Veterans Affairs Medical Center Mental Health Clinic and
      collaborative VA-U.S. Army Fort Bragg Warrior Transition Telepsychiatry Clinic.
      PRACTICE DESCRIPTION: Veterans at the VA; soldiers that have severe medical and
      mental health problems in the Warrior Transition Telepsychiatry Clinic. MAIN
      OUTCOME MEASURE(S): No response: no change in frequency and/or severity of
      nightmares; partial response: decrease in frequency and/or severity of
      nightmares; full response: total cessation of recall of nightmares. RESULTS: The
      four individuals included one active duty soldier and three veterans, ranging
      from 40 to 76 years of age. All served in the infantry, each in a different
      combat theater. Two participants had a reduction in the frequency and severity of
      nightmares at risperidone 1 mg at night. One veteran with blood alcohol levels
      greater than 300 mg/mL had a partial response with risperidone 3 mg at night.
      Without active substance abuse, the four individuals had a total cessation of
      nightmares the first night at a risperidone dose of 2 mg at night. The total
      cessation of nightmares with risperidone continued despite changes in concurrent
      antidepressants, anxiolytics, and hypnotics. No medication side effects were
      reported. CONCLUSION: The use of low-dose risperidone (1-3 mg) at night can
      reduce the severity and frequency or stop the recall of PTSD combat nightmares in
      some veterans and active duty soldiers. Risperidone may be an effective
      medication for combat nightmares of PTSD and merits additional exploration.

PMID- 22155576
TI  - C-reactive protein: the evolution of a laboratory test.

PMID- 22155577
TI  - Development of an indirect ELISA method for the parallel measurement of IgG and
      IgM antibodies against Crimean-Congo haemorrhagic fever (CCHF) virus using
      recombinant nucleoprotein as antigen.
AB  - Recombinant nucleoprotein from Crimean-Congo Haemorrhagic Fever (CCHF) virus was
      successfully derived from a baculovirus expression system and purified for use in
      a novel enzyme-linked immunosorbent assay (ELISA) diagnostic test. Comparable
      tests were used for detection of IgG and IgM antibodies, thus allowing efficient
      detection of both antibodies in parallel. The major benefits of the assay also
      included removing any requirement for polyclonal sera, thus eliminating variation
      in preparations and allowing standardisation between laboratories. The assay was
      successfully tested using a panel of positive sera supplied from samples
      identified as being positive in Turkey, Tajikistan and Kosovo and shown to be
      sensitive and specific. It is envisaged that this simple diagnostic ELISA for
      CCHF virus infection which removes the reliance on polyclonal antibody
      preparations, will be accessible to a wider range of laboratories enabling them
      to carry out routine diagnosis. This will improve the efficiency of diagnosis and
      subsequent management of infected patients.

PMID- 22155578
TI  - A quantitative comet infection assay for influenza virus.
AB  - The virus comet assay is a cell-based virulence assay used to evaluate an
      antiviral drug or antibody against a target virus. The comet assay differs from
      the plaque assay in allowing spontaneous flows in 6-well plates to spread virus.
      When implemented quantitatively the comet assay has been shown to have an order
      of-magnitude greater sensitivity to antivirals than the plaque assay. In this
      study, a quantitative comet assay for influenza virus is demonstrated, and is
      shown to have a 13-fold increase in sensitivity to ribavirin. AX4 cells (MDCK
      cells with increased surface concentration of alpha2-6 sialic acid, the influenza
      virus receptor) have reduced the comet size variability relative to MDCK cells,
      making them a better host cell for use in this assay. Because of enhanced
      antiviral sensitivity in flow-based assays, less drug is required, which could
      lead to lower reagent costs, reduced cytotoxicity, and fewer false-negative drug
      screen results. The comet assay also serves as a readout of flow conditions in
      the well. Observations from comets formed at varying humidity levels indicate a
      role for evaporation in the mechanism of spontaneous fluid flow in wells.

PMID- 22155579
TI  - Detection of enterovirus 71 using reverse transcription loop-mediated isothermal
      amplification (RT-LAMP).
AB  - Reverse transcription loop-mediated isothermal amplification (RT-LAMP), which is
      a visual assay for nucleic acids, is performed in a single step using one tube at
      65  degrees C for 1.5 h. In this study, RT-LAMP was established as a method for
      the detection of enterovirus 71 (EV71). The detection limit of the assay was
      approximately 10 copies, and no cross-reactivity was noted with Coxsackievirus
      A16, echovirus, human rotavirus (HRV) or norovirus. This assay, which offers
      greater sensitivity at a lower cost compared with the conventional reverse
      transcription polymerase chain reaction (RT-PCR), was validated using 252
      clinical specimens that had been confirmed by laboratory diagnosis using RT-PCR.
      Both methods produced the same results with 52 positive samples. The RT-LAMP
      based assay does not require specialised equipment, and therefore, it can be
      performed conveniently during an outbreak or under field conditions. In brief,
      the RT-LAMP-based assay provided a simple, rapid and efficient method for the
      detection of EV71 nucleic acid under field conditions.

PMID- 22155580
TI  - Addition of exogenous polypeptides on the mammalian reovirus outer capsid using
      reverse genetics.
AB  - Addition of exogenous peptide sequences on viral capsids is a powerful approach
      to study the process of viral infection or to retarget viruses toward defined
      cell types. Until recently, it was not possible to manipulate the genome of
      mammalian reovirus and this was an obstacle to the addition of exogenous sequence
      tags onto the capsid of a replicating virus. This obstacle has now been overcome
      by the availability of the plasmid-based reverse genetics system. In the present
      study, reverse genetics was used to introduce different exogenous peptides, up to
      40 amino acids long, at the carboxyl-terminal end of the sigma1 outer capsid
      protein. The tagged viruses obtained were infectious, produce plaques of similar
      size, and could be easily propagated at high titers. However, attempts to
      introduce a 750 nucleotides-long sequence failed, even when it was added after
      the stop codon, suggesting a possible size limitation at the nucleic acid level.

PMID- 22155581
TI  - Effect of vitamin C depletion on UVR-B induced cataract in SMP30/GNL knockout
      mice.
AB  - We investigated whether decreased vitamin C (VC) in a mouse model increases lens
      opacity (cataract) induced by in vivo exposure to ultraviolet radiation type B
      (UVR-B). Senescence marker protein-30 (SMP30) knockout (KO) mice, which cannot
      synthesize VC due to genetic disruption of the gluconolactonase (GNL) gene, were
      divided into 2 groups: VC sufficient (VC (+)) and VC deficient (VC (-)). Starting
      at 1 month of age, these groups had free access to water containing 0.0375 and
      1.5 g/L of VC, respectively. SMP30 KO VC (-), SMP30 KO VC (+), and wild-type (WT)
      mice, all 14 weeks of age, were unilaterally exposed in vivo to UVR-B (200
      mW/cm(2)) for 100 s twice a week for 3 weeks (total: 1200 mJ/cm(2)). At 48 h
      after the last UVR-B exposure, cataract morphology was documented, and the ratio
      of cataract induction was quantified as the cataract area ratio (opacity
      area/anterior capsule). UVR-B exposure induced cataract mainly at anterior sub
      capsular in SMP30 KO VC (-), SMP30 KO VC (+), and WT mice. In SMP30 KO VC (-)
      lenses the opacities were more extensive than in SMP30 KO VC (+) or WT lenses
      (cataract area ratios: 59.3% +/- 10% vs. 32.2% +/- 11.7% or 29.0% +/- 9.0%; P <
      0.01). In conclusion, VC depletion may increase the susceptibility to develop UVR
      B induced cataracts in mice unable to endogenously produce VC.

PMID- 22155582
TI  - Composition and proteolytic processing of corneal deposits associated with
      mutations in the TGFBI gene.
AB  - Different types of granular corneal dystrophy (GCD) and lattice corneal dystrophy
      (LCD) are associated with mutations in the transforming growth factor beta
      induced gene (TGFBI). These dystrophies are characterized by the formation of non
      amyloid granular deposits (GCDs) and amyloid (LCD type 1 and its variants) in the
      cornea. Typical corneal non-amyloid deposits from GCD type 2 (R124H), amyloid
      from a variant of LCD type 1 (V624M) and disease-free tissue controls were
      procured by laser capture microdissection and analyzed by tandem mass
      spectrometry. Label-free quantitative comparisons of deposits and controls
      suggested that the non-amyloid sample (R124H) specifically accumulated
      transforming growth factor beta induced protein (TGFBIp/keratoepithelin/betaig
      h3), serum amyloid P-component, clusterin, type III collagen, keratin 3, and
      histone H3-like protein. The amyloid (V624M) similarly accumulated serum amyloid
      P-component and clusterin but also a C-terminal fragment of TGFBIp containing
      residues Y571-R588 derived from the fourth fasciclin-1 domain (FAS1-4),
      apolipoprotein E and apolipoprotein A-IV. Significantly, analyses of the amyloid
      sample also revealed the presence of the serine protease Htr (High-temperature
      requirement) A1 and a number of proteolytic cleavage sites in the FAS1-4 domain
      of TGFBIp. These cleavage sites were consistent with the ligand binding and
      proteolytic activity of HtrA1 suggesting that it plays a role in the proteolytic
      processing of the amyloidogenic FAS1-4 domain. Taken together, the data suggest
      that the amyloidogenic-prone region of the fourth FAS1 domain of TGFBIp
      encompasses the Y571-R588 peptide and that HtrA1 is involved in the proteolytic
      processing of TGFBIp-derived amyloid in vivo.

PMID- 22155584
TI  - A right-sided aortic arch and aberrant left subclavian artery with proximal
      segment hypoplasia.
AB  - The right-sided thoracic aortic arch is a rare congenital malformation occurring
      during embryologic development. A majority of the cases present with two anatomic
      variations, one of which is an aberrant left subclavian artery (LSA) originating
      off the distal descending aortic arch. This aberrant LSA courses across and
      compresses thoracic structures on its way to the left thoracic outlet. While this
      aberrant vessel causes mostly benign symptoms, patients may first present with
      rupture of a thoracic aneurysm. This thoracic aneurysm is commonly known as
      Kommerell's diverticulum. This paper presents a case of an aberrant LSA
      originating off Kommerell's diverticulum with a proximal long-segment hypoplasia,
      a very rare anatomic variation.

PMID- 22155583
TI  - Rapidly expanding genetic diversity and host range of the Circoviridae viral
      family and other Rep encoding small circular ssDNA genomes.
AB  - The genomes of numerous circoviruses and distantly related circular ssDNA viruses
      encoding a rolling circle replication initiator protein (Rep) have been
      characterized from the tissues of mammals, fish, insects, plants (geminivirus and
      nanovirus), in human and animal feces, in an algae cell, and in diverse
      environmental samples. We review the genome organization, phylogenetic
      relationships and initial prevalence studies of cycloviruses, a proposed new
      genus in the Circoviridae family. Viral fossil rep sequences were also recently
      identified integrated on the chromosomes of mammals, frogs, lancelets,
      crustaceans, mites, gastropods, roundworms, placozoans, hydrozoans, protozoans,
      land plants, fungi, algae, and phytoplasma bacterias and their plasmids,
      reflecting the very wide past host range of rep bearing viruses. An ancient
      origin for viruses with Rep-encoding small circular ssDNA genomes, predating the
      diversification of eukaryotes, is discussed. The cellular hosts and pathogenicity
      of many recently described rep-containing circular ssDNA genomes remain to be
      determined. Future studies of the virome of single cell and multi-cellular
      eukaryotes are likely to further extend the known diversity and host-range of
      small rep-containing circular ssDNA viral genomes.

PMID- 22155585
TI  - Detection of human G10 rotavirus strains with similarity to bovine and bovine
      like equine strains from untypable samples.
AB  - G10 rotaviruses, which are usually found in cattle, have also been reported in
      neonatal infections in recent years. During the rotavirus surveillances of
      children less than 4years of age between 2003 and 2006 in Kolkata, eastern India,
      60 out of 1153 samples could not be typed. All 60 samples gave usual
      electropherotype pattern in polyacrylamide gel. Thirty-one out of these 60 G and
      P untypable rotavirus strains were successfully characterized during the study.
      Among 31 samples, G9P[4] (n=8), G12P[8] (n=8), G1P[8] (n=6), G10P[4] (n=6), and
      G2P[4] (n=3) genotypes were identified. In this study we report genetic analysis
      of the six G10 strains, which revealed close relations with Turkish (E29TR)
      bovine strains, as well as with bovine-like-equine strain (Erv2) from India.
      SimPlot of the VP7 gene segment suggested possible recombination event between
      the bovine and the bovine-like-equine rotaviruses in these human rotavirus
      infections.

PMID- 22155586
TI  - An integrative functional genomics approach for discovering biomarkers in
      schizophrenia.
AB  - Schizophrenia (SZ) is a complex disorder resulting from both genetic and
      environmental causes with a lifetime prevalence world-wide of 1%; however, there
      are no specific, sensitive and validated biomarkers for SZ. A general unifying
      hypothesis has been put forward that disease-associated single nucleotide
      polymorphisms (SNPs) from genome-wide association study (GWAS) are more likely to
      be associated with gene expression quantitative trait loci (eQTL). We will
      describe this hypothesis and review primary methodology with refinements for
      testing this paradigmatic approach in SZ. We will describe biomarker studies of
      SZ and testing enrichment of SNPs that are associated both with eQTLs and
      existing GWAS of SZ. SZ-associated SNPs that overlap with eQTLs can be placed
      into gene-gene expression, protein-protein and protein-DNA interaction networks.
      Further, those networks can be tested by reducing/silencing the gene expression
      levels of critical nodes. We present pilot data to support these methods of
      investigation such as the use of eQTLs to annotate GWASs of SZ, which could be
      applied to the field of biomarker discovery. Those networks that have association
      with SNP markers, especially cis-regulated expression, might lead to a more clear
      understanding of important candidate genes that predispose to disease and alter
      expression. This method has general application to many complex disorders.

PMID- 22155588
TI  - The joint allele frequency spectrum of multiple populations: a coalescent theory
      approach.
AB  - The allele frequency spectrum is a series of statistics that describe genetic
      polymorphism, and is commonly used for inferring population genetic parameters
      and detecting natural selection. Population genetic theory on the allele
      frequency spectrum for a single population has been well studied using both
      coalescent theory and diffusion equations. Recently, the theory was extended to
      the joint allele frequency spectrum (JAFS) for three populations using diffusion
      equations and was shown to be very useful in inferring human demographic history.
      In this paper, I show that the JAFS can be analytically derived with coalescent
      theory for a basic model of two isolated populations and then extended to
      multiple populations and various complex scenarios, such as those involving
      population growth and bottleneck, migration, and positive selection. Simulation
      study is used to demonstrate the accuracy and applicability of the theoretical
      model. The coalescent theory-based approach for the JAFS can characterize the
      demographic history with comprehensive statistical models as the diffusion
      approach does, and in addition gains several novel advantages: the computational
      complexity of calculating the JAFS with coalescent theory is reduced, and thus it
      is feasible to analytically obtain the JAFS for multiple populations; the
      hitchhiking effect can be efficiently modeled in coalescent theory, enabling the
      development of methodologies for detecting selection via multi-population
      polymorphism data. As an alternative to the diffusion approximation approach, the
      coalescent theory for the JAFS also provides a foundation for population genetic
      inference with the advent of large-scale genomic polymorphism data.

PMID- 22155587
TI  - Diagnosis of osteoarthritis: imaging.
AB  - Osteoarthritis (OA) is a chronic, debilitating joint disease characterized by
      degenerative changes to the bones, cartilage, menisci, ligaments, and synovial
      tissue. Imaging modalities such as radiography, magnetic resonance imaging (MRI),
      optical coherence tomography (OCT), and ultrasound (US) permit visualization of
      these structures and can evaluate disease onset and progression. Radiography is
      primarily useful for the assessment of bony structures, while OCT is used for
      evaluation of articular cartilage and US for ligaments and the synovium. MRI
      permits visualization of all intraarticular structures and pathologies, though US
      or OCT may be preferential in some circumstances. As OA is a disease of the whole
      joint, a combination of imaging techniques may be necessary in order to gain the
      most comprehensive picture of the disease state. This article is part of a
      Special Issue entitled "Osteoarthritis".

PMID- 22155589
TI  - A systematic review of the literature for evidence on health facility committees
      in low- and middle-income countries.
AB  - Community participation in health (CPH) has been advocated as a health-improving
      strategy for many decades. However, CPH comes in many different forms, one of
      which is the use of health facility committees (HFCs) on which there is community
      representation. This paper presents the findings of a systematic literature
      review of: (a) the evidence of HFCs' effectiveness, and (b) the factors that
      influence the performance and effectiveness of HFCs. Four electronic databases
      and the websites of eight key organizations were searched. Out of 341 potentially
      relevant publications, only four provided reasonable evidence of the
      effectiveness of HFCs. A further 37 papers were selected and used to draw out
      data on the factors that influence the functioning of HFCs. A conceptual model
      was developed to describe the key factors. It consists of, firstly, the features
      of the HFC, community and facility, and their interactions; secondly, process
      factors relating to the way HFCs are established and supported; and finally, a
      set of contextual factors. The review found some evidence that HFCs can be
      effective in terms of improving the quality and coverage of health care, as well
      as impacting on health outcomes. However, the external validity of these studies
      is inevitably limited. Given the different potential roles/functions of HFCs and
      the complex and multiple set of factors influencing their functioning, there is
      no 'one size fits all' approach to CPH via HFCs, nor to the evaluation of HFCs.
      However, there are plenty of experiences and lessons in the literature which
      decision makers and managers can use to optimize HFCs.

PMID- 22155590
TI  - How to do (or not to do) ... Tracking data on development assistance for health.
AB  - Development assistance for health (DAH) has increased substantially in recent
      years and is seen as important to the improvement of health and health systems in
      developing countries. As a result, there has been increasing interest in tracking
      and understanding these resource flows from the global health community. A number
      of datasets, each with its own strengths and weaknesses, are available to track
      DAH. In this article we review the available datasets on DAH and summarize the
      strengths and weaknesses of each of these datasets to help researchers make the
      best choice of which to use to inform their analysis. Finally, we also provide
      recommendations about how each of these datasets could be improved.

PMID- 22155591
TI  - In vivo characterisation of a novel water-soluble Cyclosporine A prodrug for the
      treatment of dry eye disease.
AB  - Cyclosporine A (CsA) has been demonstrated to be effective for the treatment of a
      variety of ophthalmological conditions, including ocular surface disorders such
      as the dry eye disease (DED). Since CsA is characterised by its low water
      solubility, the development of a topical ophthalmic formulation represents an
      interesting pharmaceutical question. In the present study, two different
      strategies to address this challenge were studied and compared: (i) a water
      soluble CsA prodrug formulated within an aqueous solution and (ii) a CsA oil-in
      water emulsion (Restasis, Allergan Inc., Irvine, CA). First, the prodrug
      formulation was shown to have an excellent ocular tolerance as well as no
      influence on the basal tear production; maintaining the ocular surface properties
      remained unchanged. Then, in order to allow in vivo investigations, a specific
      analytical method based on ultra high pressure liquid chromatography coupled with
      triple quadrupole mass spectrometer (UHPLC-MS/MS) was developed and optimised to
      quantify CsA in ocular tissues and fluids. The CsA ocular kinetics in lachrymal
      fluid for both formulations were found to be similar between 15 min and 48 h. The
      CsA ocular distribution study evidenced the ability of the prodrug formulation to
      penetrate into the eye, achieving therapeutically active CsA levels in tissues of
      both the anterior and posterior segments. In addition, the detailed analysis of
      the in vivo data using a bicompartmental model pointed out a higher
      bioavailability and lower elimination rate for CsA when it is generated from the
      prodrug than after direct application as an emulsion. The interesting in vivo
      properties displayed by the prodrug solution make it a safe and suitable option
      for the treatment of DED.

PMID- 22155592
TI  - Chemical analysis of Penstemon campanulatus (Cav.) Willd.--antimicrobial
      activities.
AB  - A new iridoid glucoside named 10-isovaleroyl-dihydropenstemide (1), along with
      nine known compounds was isolated from the aerial part of Penstemon campanulatus
      (Cav.) Willd. The known compounds include three iridoid glucosides, one
      phenylpropanoid glucoside, one monoterpene glucoside, one monoterpene lactone and
      three flavonoids. Their structures were elucidated on the basis of spectral
      evidence. Additionally four phenolic acids as well as a fatty acid were
      determined through GC-MS analysis. All isolated compounds and the crude extracts
      were assayed for their antimicrobial activities against six Gram positive and
      negative bacteria, as well as against three human pathogenic fungi.

PMID- 22155593
TI  - The potential health effects of Melicoccus bijugatus Jacq. fruits: phytochemical,
      chemotaxonomic and ethnobotanical investigations.
AB  - Most natural product research is market-driven and thus many plant species are
      overlooked for their health value due to lack of financial incentives. This may
      explain the limited information available about the health effects of the edible
      fruit species Melicoccus bijugatus, a member of the Sapindaceae family that grows
      mostly in the Caribbean and in parts of South America. However, recent
      phytochemical studies of these fruits have shed some light on their biological
      effects. In this review the health effects of M. bijugatus fruit pulp and seeds
      are assessed in relation to phytochemical and ethnobotanical studies, as well as
      chemotaxonomic information and medicinal uses of other Sapindaceae species. The
      chemistry of M. bijugatus fruits was found to be different than the other
      Sapindaceae fruits, although some of the medicinal uses were similar. Specific
      phenolics or sugars in M. bijugatus fruits may contribute to their therapeutic
      uses, especially for gastrointestinal problems, and to some extent toxicological
      effects. This review focuses our understanding about the specific biological
      effects of M. bijugatus fruits, which may be useful for predicting other
      medicinal uses, potential drug or food interactions and may benefit people where
      the fruits are prevalent and healthcare resources are scarce.

PMID- 22155594
TI  - Bioactive polar compounds from stem bark of Magnolia officinalis.
AB  - Two new phenylethanoid glycosides magnoloside D (1) and E (2), together with nine
      known compounds, were isolated from the polar part of methanol extract of the
      stem bark of Magnolia officinalis. The structures of the new compounds were
      established on the basis of spectral analysis. Anti-spasmodic activity of four
      major constituents (3, 4, 9 and 11) was tested in isolated colon of rat,
      compounds 3, 4, and 9 showed inhibition against acetylcholine, with the effect
      similar to that of magnolol and honokiol. At the same time, antioxidant activity
      of the isolated compounds was investigated using a DPPH and an ORAC assay. All of
      the compounds, except compound 8 showed potent antioxidant capacity in the ORAC
      assay, while compounds 1-5 and 11 exhibited potent antioxidant activity in the
      DPPH assay.

PMID- 22155595
TI  - Molecular response of Musca domestica L. to Mintostachys verticillata essential
      oil, (4R)+-pulegone and menthone.
AB  - Intense applications of synthetic insecticides for the control of adult Musca
      domestica have led to the insects developing resistance to most of them. In
      consequence, there is interest in new active ingredients as alternatives to
      conventional insecticides. Essential oils (EO) are potential tools for
      controlling M. domestica because of their effectiveness and their minimal
      environmental effects. In a fumigant assay, M. domestica adults treated with
      Minthostachys verticillata EO [LC(50)=0.5 mg/dm(3); majority components by SPME
      GC: (4R)(+)-pulegone (67.5%), menthone (22.3%) and (4R)(+)-limonene (3.8%)], died
      within 15 min or less. The terpenes absorbed by the flies and their metabolites,
      analyzed using SPME fiber, were (4R)(+)-limonene (LC(50)=6.2 mg/dm(3)), menthone
      (LC(50)=1.9 mg/dm(3)), (4R)(+)-pulegone (LC(50)=1.7 mg/dm(3)) and a new
      component, menthofuran (LC(50)=0.3 mg/dm(3)), in a relative proportion of 12.4,
      6.5, 35.9 and 44.2% respectively. Menthofuran was formed by oxidation of either
      (4R)(+)-pulegone or menthone mediated by cytochrome P450, as demonstrated by a
      fumigation assay on flies previously treated with piperonyl butoxide, a P450
      inhibitor, which showed a decrease in toxicity of the EO, (4R)(+)-pulegone and of
      menthone, supporting the participation of the P450 oxidizing system in the
      formation of menthofuran. The enzymatic reaction of isolated fly microsomes with
      the EO or the (4R)(+)-pulegone produced menthofuran in both cases. Contrary to
      expectations, the insect detoxification system contributed to enhance the
      toxicity of the M. verticillata EO. Consequently, resistant strains
      overexpressing P450 genes will be more susceptible to either M. verticillata EO
      or (4R)(+)-pulegone and menthone.

PMID- 22155596
TI  - Bioassay-guided isolation of vasorelaxant compounds from Ziziphora clinopodioides
      Lam. (Lamiaceae).
AB  - Ziziphora clinopodioides Lam. (Lamiaceae) is traditionally used in Uighur's
      medicine for the treatment of hypertension. Our study determined and evaluated
      the bioactive compounds by performing an activity-guided fractionation of a
      hydroalcoholic extract of the whole plant, using an in vitro model of rat
      isolated thoracic aortic rings. Seven compounds were identified as active
      principles: acacetin, apigenin, chrysin, thymonin, acetovanillone, 4
      hydroxyacetophenone and ethyl 4-coumarate. Apigenin, chrysin and ethyl 4
      coumarate were found to be the most effective. Our results provide the first
      evidence that the vasodilation induced by Z. clinopodioides Lam. is mediated, at
      least in part, by phenolic components.

PMID- 22155597
TI  - A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined
      modulation of Na(v)1.5 and K(v)4.3 channel currents.
AB  - BACKGROUND: Cardiac sodium channel beta-subunit mutations have been associated
      with several inherited cardiac arrhythmia syndromes. OBJECTIVE: To identify and
      characterize variations in SCN1Bb associated with Brugada syndrome (BrS) and
      sudden infant death syndrome (SIDS). METHODS: All known exons and intron borders
      of the BrS-susceptibility genes were amplified and sequenced in both directions.
      Wild type (WT) and mutant genes were expressed in TSA201 cells and studied using
      co-immunoprecipitation and whole-cell patch-clamp techniques. RESULTS: Patient 1
      was a 44-year-old man with an ajmaline-induced type 1 ST-segment elevation in V1
      and V2 supporting the diagnosis of BrS. Patient 2 was a 62-year-old woman
      displaying a coved-type BrS electrocardiogram who developed cardiac arrest during
      fever. Patient 3 was a 4-month-old female SIDS case. A R214Q variant was detected
      in exon 3A of SCN1Bb (Na(v)1B) in all three probands, but not in any other gene
      previously associated with BrS or SIDS. R214Q was identified in 4 of 807
      ethnically-matched healthy controls (0.50%). Co-expression of SCN5A/WT +
      SCN1Bb/R214Q resulted in peak sodium channel current (I(Na)) 56.5% smaller
      compared to SCN5A/WT + SCN1Bb/WT (n = 11-12, P<0.05). Co-expression of KCND3/WT +
      SCN1Bb/R214Q induced a Kv4.3 current (transient outward potassium current, I(to))
      70.6% greater compared with KCND3/WT + SCN1Bb/WT (n = 10-11, P<0.01). Co
      immunoprecipitation indicated structural association between Na(v)beta1B and
      Na(v)1.5 and K(v)4.3. CONCLUSION: Our results suggest that R214Q variation in
      SCN1Bb is a functional polymorphism that may serve as a modifier of the substrate
      responsible for BrS or SIDS phenotypes via a combined loss of function of sodium
      channel current and gain of function of transient outward potassium current.

PMID- 22155598
TI  - SCN1Bb R214Q found in 3 patients: 1 with Brugada syndrome and 2 with lone atrial
      fibrillation.
AB  - BACKGROUND: SCN1Bb encodes the beta-subunit of the sodium channel. A mutation in
      SCN1Bb R214Q has recently been shown both to increase the Kv4.3 current and to
      decrease the sodium current. The variant was suggested to increase the
      susceptibility to Brugada syndrome (BrS). OBJECTIVE: To sequence a population of
      BrS and early-onset lone atrial fibrillation (AF) patients for the R214Q mutation
      in the SCN1Bb gene. METHODS: The coding sequence and splice junctions of SCN1Bb
      were bidirectionally sequenced by using Big Dye chemistry in 192 early-onset lone
      AF patients and 22 BrS patients. RESULTS: Three probands carrying the R214Q
      variant were identified. No mutations were identified in genes previously
      associated with BrS or AF in these patients. Case 1 also had the onset of
      persistent lone AF at the age of 39 years. Case 2 was a lone AF case with onset
      at the age of 39 years and paroxysmal lone AF. Case 3 was a BrS patient with a
      type 1 electrocardiogram and onset of disease at the age of 54 years. Both lone
      AF patients had electrocardiograms that raised the suspicion of BrS, but
      intravenous flecainide testing was, in both cases, negative. R214Q was not
      present in the control group (n = 216) and has not previously been reported in
      conjunction to AF. CONCLUSION: Three patients of 192 young lone AF and 22 BrS
      patients carried the nonsynonymous R214Q mutations in SCN1Bb, thereby indicating
      that this variant increases the susceptibility to both BrS and AF.

PMID- 22155599
TI  - Novel cationic liposomes provide highly efficient delivery of DNA and RNA into
      dendritic cell progenitors and their immature offsets.
AB  - Here we report on the application of cationic liposomes formed by new cationic
      lipids and the lipid-helper DOPE (dioleoylphosphatidylethanolamine) for the
      transfection of plasmid DNA and mRNA into dendritic cells (DCs) progenitors and
      immature DCs of bone-marrow origin in vitro and the use of these DCs to induce
      the suppression of B16 melanoma metastases in vivo. The cationic lipids contain
      one (X2, S1, S2 and S3) or two (2X3) cholesterol residues or long-chain
      hydrocarbon substituent (2D3) linked with spermine. Data show that liposomes 2X3
      DOPE, 2D3-DOPE, X2-DOPE and S2-DOPE display high transfection efficiency in
      respect to DNA (30-47% of DC progenitors and up to 57% of immature DC were
      transfected) and RNA (up to 57% of cells were transfected). The studied lipids
      exhibited an efficiency of DNA and RNA delivery in DCs several times higher in
      comparison with Lipofectamine 2000. Observed ex vivo the higher transfection
      efficiencies of DCs with mRNAs encoding of a set of tumor-associated antigens
      provided by cationic liposomes 2X3-DOPE and 2X2-DOPE corresponded to a 3-5 fold
      suppression of metastasis number in a model of murine B16 melanoma in vivo. The
      injection into mice of these pulsed DCs resulted in a slight pro-inflammatory
      response which was balanced by the positive effect of the antitumor cytokine
      production induced by the DCs. The obtained data show that the novel spermine
      based polycationic lipids can be applied in the preparation of antitumor DC-based
      vaccine.

PMID- 22155600
TI  - Guest editorial: visionary genomics.

PMID- 22155602
TI  - Role of CYP2E1 genotypes in susceptibility to colorectal cancer in the Kashmiri
      population.
AB  - Cytochrome P450 2E1 (CYP2E1) is a key enzyme involved in the metabolic activation
      of procarcinogens such as N-nitrosoamines and low-molecular-weight organic
      compounds. The main aim of this study was to determine whether CYP450 2E1
      polymorphisms are associated with the risk of colorectal cancer (CRC). We
      investigated the genotype distribution of the CYP2E1 gene RsaI and a 96-base pair
      (bp) insertion in 86 CRC cases in comparison with 160 healthy subjects. We found
      the frequency of the CYP2E1 RsaI genotype to be 53.5 per cent (46/86) for c1/c1,
      17.4 per cent (15/86) for c1/c2 and 29.1 per cent (25/86) for c2/c2, and the
      CYP2E1 98-bp insertion frequencies to be 63.9 per cent (55/86) for non-insertion
      (i/i), 22.1 per cent (19/86) for heterozygous insertion (i/I) and 36.0 per cent
      (12/86) for homozygous insertion (I/I) among CRC cases. We also found the CYP2E1
      RsaI c2/c2 and CYP2E1 98-bp heterozygous i/I genotypes to be significantly
      associated with an increased risk of CRC (p = 0.01). We suggest that CYP2E1
      polymorphisms are involved in the susceptibility to developing CRC in the ethnic
      Kashmiri population.

PMID- 22155604
TI  - The role of ALDH2 and ADH1B polymorphism in alcohol consumption and stroke in Han
      Chinese.
AB  - The genes encoding the enzymes for metabolising alcohol dehydrogenase 1B (ADH1B)
      and aldehyde dehydrogenase 2 (ALDH2) - exhibit genetic polymorphism and ethnic
      variations. Although the ALDH2*2 variant allele has been widely accepted as
      protecting against the development of alcoholism in Asians, the association of
      the ADH1B*2 variant allele with drinking behaviour remains inconclusive. The goal
      of this study was to determine whether the polymorphic ADH1B and ALDH2 genes are
      associated with stroke in male Han Chinese with high alcohol consumption. Sixty
      five stroke patients with a history of heavy drinking (HDS) and 83 stroke
      patients without such a history (NHDS) were recruited for analysis of the ADH1B
      and ALDH2 genotypes from the stroke registry in the Tri-Service General Hospital,
      Taipei, Taiwan, between January 2000 and December 2001. The allelotypes of ADH1B
      and ALDH2 were determined using the polymerase chain reaction-restriction
      fragment length polymorphism method. The HDS patients (3 per cent) showed a
      significantly lower ALDH2*2 allele frequency than NHDS patients (27 per cent) (p
      < 0.001). After controlling for age, patients with HDS were associated with a
      significantly higher occurrence of cigarette smoking (p < 0.01) and liver
      dysfunction (p < 0.01). Multiple logistic regression analyses revealed that the
      ALDH2*2 variant allele was an independent variable exhibiting strong protection
      (odds ratio 0.072; 95 per cent confidence interval 0.02-0.26) against HDS after
      adjustment for hypertension, diabetes mellitus, smoking status and liver
      dysfunction. By contrast, allelic variations in ADH1B exerted no significant
      effect on HDS. The present study indicated that, unlike ALDH2*2, ADH1B*2 appears
      not to be a significant negative risk factor for high alcohol consumption in male
      Han Chinese with stroke.

PMID- 22155603
TI  - Systems biology-based analysis implicates a novel role for vitamin D metabolism
      in the pathogenesis of age-related macular degeneration.
AB  - Vitamin D has been shown to have anti-angiogenic properties and to play a
      protective role in several types of cancer, including breast, prostate and
      cutaneous melanoma. Similarly, vitamin D levels have been shown to be protective
      for risk of a number of conditions, including cardiovascular disease and chronic
      kidney disease, as well as numerous autoimmune disorders such as multiple
      sclerosis, inflammatory bowel diseases and type 1 diabetes mellitus. A study
      performed by Parekh et al. was the first to suggest a role for vitamin D in age
      related macular degeneration (AMD) and showed a correlation between reduced serum
      vitamin D levels and risk for early AMD. Based on this study and the protective
      role of vitamin D in diseases with similar pathophysiology to AMD, we examined
      the role of vitamin D in a family-based cohort of 481 sibling pairs. Using
      extremely phenotypically discordant sibling pairs, initially we evaluated the
      association of neovascular AMD and vitamin D/sunlight-related epidemiological
      factors. After controlling for established AMD risk factors, including
      polymorphisms of the genes encoding complement factor H (CFH) and age-related
      maculopathy susceptibility 2/HtrA serine peptidase (ARMS2/HTRA1), and smoking
      history, we found that ultraviolet irradiance was protective for the development
      of neovascular AMD (p = 0.001). Although evaluation of serum vitamin D levels (25
      hydroxyvitamin D [25(OH)D]) was higher in unaffected individuals than in their
      affected siblings, this finding did not reach statistical significance. Based on
      the relationship between ultraviolet irradiance and vitamin D production, we
      employed a candidate gene approach for evaluating common variation in key vitamin
      D pathway genes (the genes encoding the vitamin D receptor [VDR]; cytochrome
      P450, family 27, subfamily B, polypeptide 1 [CYP27B1]; cytochrome P450, family
      24, subfamily A, polypeptide 1 [CYP24A1]; and CYP27A1) in this same family-based
      cohort. Initial findings were then validated and replicated in the extended
      family cohort, an unrelated case-control cohort from central Greece and a
      prospective nested case-control population from the Nurse's Health Study and
      Health Professionals Follow-Up Studies, which included patients with all subtypes
      of AMD for a total of 2,528 individuals. Single point variants in CYP24A1 (the
      gene encoding the catabolising enzyme of the vitamin D pathway) were demonstrated
      to influence AMD risk after controlling for smoking history, sex and age in all
      populations, both separately and, more importantly, in a meta-analysis. This is
      the first report demonstrating a genetic association between vitamin D metabolism
      and AMD risk. These findings were also supplemented with expression data from
      human donor eyes and human retinal cell lines. These data not only extend
      previous biological studies in the AMD field, but further emphasise common
      antecedents between several disorders with an inflammatory/immunogenic component
      such as cardiovascular disease, cancer and AMD.

PMID- 22155606
TI  - Neurofibromatosis type 1-associated tumours: their somatic mutational spectrum
      and pathogenesis.
AB  - Somatic gene mutations constitute key events in the malignant transformation of
      human cells. Somatic mutation can either actively speed up the growth of tumour
      cells or relax the growth constraints normally imposed upon them, thereby
      conferring a selective (proliferative) advantage at the cellular level.
      Neurofibromatosis type-1 (NF1) affects 1/3,000-4,000 individuals worldwide and is
      caused by the inactivation of the NF1 tumour suppressor gene, which encodes the
      protein neurofibromin. Consistent with Knudson's two-hit hypothesis, NF1 patients
      harbouring a heterozygous germline NF1 mutation develop neurofibromas upon
      somatic mutation of the second, wild-type, NF1 allele. While the identification
      of somatic mutations in NF1 patients has always been problematic on account of
      the extensive cellular heterogeneity manifested by neurofibromas, the
      classification of NF1 somatic mutations is a prerequisite for understanding the
      complex molecular mechanisms underlying NF1 tumorigenesis. Here, the known
      somatic mutational spectrum for the NF1 gene in a range of NF1-associated
      neoplasms - including peripheral nerve sheath tumours (neurofibromas), malignant
      peripheral nerve sheath tumours, gastrointestinal stromal tumours, gastric
      carcinoid, juvenile myelomonocytic leukaemia, glomus tumours, astrocytomas and
      phaeochromocytomas - have been collated and analysed.

PMID- 22155607
TI  - Update of the human secretoglobin (SCGB) gene superfamily and an example of
      'evolutionary bloom' of androgen-binding protein genes within the mouse Scgb gene
      superfamily.
AB  - The secretoglobins (SCGBs) comprise a family of small, secreted proteins found in
      animals exclusively of mammalian lineage. There are 11 human SCGB genes and five
      pseudogenes. Interestingly, mice have 68 Scgb genes, four of which are highly
      orthologous to human SCGB genes; the remainder represent an 'evolutionary bloom'
      and make up a large gene family represented by only six counterparts in humans.
      SCGBs are found in high concentrations in many mammalian secretions, including
      fluids of the lung, lacrimal gland, salivary gland, prostate and uterus. Whereas
      the biological activities of most individual SCGBs have not been fully
      characterised, what already has been discovered suggests that this family has an
      important role in the modulation of inflammation, tissue repair and
      tumorigenesis. In mice, the large Scgb1b and Scgb2b gene families encode the
      androgen-binding proteins, which have been shown to play a role in mate
      selection. Although much has been learned about SCGBs in recent years, clearly
      more research remains to be done to allow a better understanding of the roles of
      these proteins in human health and disease. Such information is predicted to
      reveal valuable novel drug targets for the treatment of inflammation, as well as
      designing biomarkers that might identify tissue damage or cancer.

PMID- 22155608
TI  - Overview of biological database mapping services for interoperation between
      different 'omics' datasets.
AB  - Many primary biological databases are dedicated to providing annotation for a
      specific type of biological molecule such as a clone, transcript, gene or
      protein, but often with limited cross-references. Therefore, enhanced mapping is
      required between these databases to facilitate the correlation of independent
      experimental datasets. For example, molecular biology experiments conducted on
      samples (DNA, mRNA or protein) often yield more than one type of 'omics' dataset
      as an object for analysis (eg a sample can have a genomics as well as proteomics
      expression dataset available for analysis). Thus, in order to map the two
      datasets, the identifier type from one dataset is required to be linked to
      another dataset, so preventing loss of critical information in downstream
      analysis. This identifier mapping can be performed using identifier converter
      software relevant to the query and target identifier databases. This review
      presents the publicly available web-based biological database identifier
      converters, with comparison of their usage, input and output formats, and the
      types of available query and target database identifier types.

PMID- 22155609
TI  - In-silico human genomics with GeneCards.
AB  - Since 1998, the bioinformatics, systems biology, genomics and medical communities
      have enjoyed a synergistic relationship with the GeneCards database of human
      genes (http://www.genecards.org). This human gene compendium was created to help
      to introduce order into the increasing chaos of information flow. As a
      consequence of viewing details and deep links related to specific genes, users
      have often requested enhanced capabilities, such that, over time, GeneCards has
      blossomed into a suite of tools (including GeneDecks, GeneALaCart, GeneLoc,
      GeneNote and GeneAnnot) for a variety of analyses of both single human genes and
      sets thereof. In this paper, we focus on inhouse and external research activities
      which have been enabled, enhanced, complemented and, in some cases, motivated by
      GeneCards. In turn, such interactions have often inspired and propelled
      improvements in GeneCards. We describe here the evolution and architecture of
      this project, including examples of synergistic applications in diverse areas
      such as synthetic lethality in cancer, the annotation of genetic variations in
      disease, omics integration in a systems biology approach to kidney disease, and
      bioinformatics tools.

PMID- 22155610
TI  - Inversion of contrast polarity abolishes spontaneous preferences for face-like
      stimuli in newborn chicks.
AB  - A spontaneous preference for face-like stimuli has been demonstrated in domestic
      chicks, similar to that shown by human newborns, suggesting evolutionary
      continuity across species. Inversion of contrast polarity of face-like stimuli
      abolishes face preferences in human newborns. Here we investigated the effects of
      contrast polarity inversion and brain lateralization in chicks' preferences for
      faces. In Experiment 1 face-naive chicks were tested with a negative face
      obtained from a stimulus that elicited preferential approach in previous
      research. As in human newborns, reversal of contrast polarity abolished face
      preferences. Experiments 2, 3 and 5 investigated the effect of adding a pupil
      like dot within the inner features of the negative and of positive stimuli (a
      manipulation that re-established face-preference in human newborns). Chicks
      reacted to this by avoiding the face stimulus. In Experiments 4 and 6 we found
      that the preference expressed by chicks having only their left eye (right
      hemisphere) in use changed according to contrast polarity, whereas it remained
      unaffected in chicks having their right eye in use. Thus, in domestic chicks, as
      in human beings, a stimulus is perceived as face-like only if it presents the
      correct luminance pattern expected for a face under natural top-lit illumination
      and the right hemisphere seems to play a crucial role in this kind of social
      orienting responses.

PMID- 22155611
TI  - Oxytocin directly administered into the nucleus accumbens core or subthalamic
      nucleus attenuates methamphetamine-induced conditioned place preference.
AB  - Accumulating evidence indicates that the neuropeptide oxytocin (OXY) may modulate
      reward-related behavioural responses to methamphetamine (METH) administration.
      Limited research has examined the effect of OXY on METH-induced conditioned place
      preference (CPP) and little is known about the neural mechanisms involved. A Fos
      immunohistochemistry study recently demonstrated that peripheral OXY
      administration reduced METH-induced Fos expression within the nucleus accumbens
      (NAc) core and subthalamic nucleus (STh) in rats. The current study aimed to (i)
      investigate the effect of systemically administered OXY on METH-induced CPP, (ii)
      determine the effectiveness of a single-trial CPP procedure with METH, in order
      to (iii) evaluate whether pretreatment with OXY injected directly into the NAc
      core or the STh attenuates METH-induced CPP. Results showed that male Sprague
      Dawley rats learned to associate unique compartmental cues with METH (1 mg/kg,
      i.p.) such that they spent more time in the METH-paired compartment and less time
      in the saline-paired compartment. Pretreatment with systemic OXY (0.6 mg, i.p.),
      or OXY (0.6 ng, i.c.) microinjected into the NAc core or the STh prior to METH
      administration attenuated the formation of a CPP to METH. This provides further
      evidence that OXY acts within either the NAc core or the STh to reduce the
      rewarding effects of METH administration.

PMID- 22155605
TI  - Human genetics and genomics a decade after the release of the draft sequence of
      the human genome.
AB  - Substantial progress has been made in human genetics and genomics research over
      the past ten years since the publication of the draft sequence of the human
      genome in 2001. Findings emanating directly from the Human Genome Project,
      together with those from follow-on studies, have had an enormous impact on our
      understanding of the architecture and function of the human genome. Major
      developments have been made in cataloguing genetic variation, the International
      HapMap Project, and with respect to advances in genotyping technologies. These
      developments are vital for the emergence of genome-wide association studies in
      the investigation of complex diseases and traits. In parallel, the advent of high
      throughput sequencing technologies has ushered in the 'personal genome
      sequencing' era for both normal and cancer genomes, and made possible large-scale
      genome sequencing studies such as the 1000 Genomes Project and the International
      Cancer Genome Consortium. The high-throughput sequencing and sequence-capture
      technologies are also providing new opportunities to study Mendelian disorders
      through exome sequencing and whole-genome sequencing. This paper reviews these
      major developments in human genetics and genomics over the past decade.

PMID- 22155612
TI  - Possible interaction between opioidergic and cholinergic systems of CA1 in
      cholestasis-induced amnesia in mice.
AB  - Bile duct ligation (BDL) induces primary biliary cirrhosis characterized by
      cholestasis, impaired liver function and cognition including impairment of memory
      formation and anxiety-like behaviors. Endogenous opioid and acetylcholine levels
      are elevated in animal model of cholestasis. In addition, there is no data about
      the effects of interaction opioidergic and cholinergic systems of dorsal
      hippocampus (CA1) on amnesia-induced by cholestasis. Male mice weighing 25-35 g
      were used in this study. Cholestasis was induced by the ligation of the common
      bile duct. One-trial step-down and hole-board paradigms were used for the
      assessment of memory retrieval and anxiety-like behaviors respectively. All drugs
      injected intra-CA1. The data showed that cholestasis (24 days after BDL)
      decreased memory retrieval. Sole intra-CA1 injection of higher dose of
      mecamylamine (0.125, 0.25, 0.5 and 1 MUg/mice) and scopolamine (0.125, 0.25, 0.5
      1 and 2 MUg/mice) but not all doses of naloxone (0.0125, 0.025 and 0.05 MUg/mice)
      decreased memory retrieval in the sham operated BDL. The ineffective doses of
      naloxone (0.025 and 0.05 MUg/mice), mecamylamine (0.5 MUg/mice) and scopolamine
      (0.5 MUg/mice) restored cholestasis-induced amnesia 24 days after BDL. Further,
      all cross co-administration ineffective doses of naloxone (0.0125 MUg/mice),
      mecamylamine (0.125 MUg/mice) and scopolamine (0.125 MUg/mice) reversed
      cholestasis-induced amnesia. All doses of the drugs have no effect on exploratory
      behaviors. The data strongly revealed that synergistic effect between opioidergic
      and cholinergic systems of CA1 on the modulation of cholestasis-induced amnesia.

PMID- 22155614
TI  - Pathway engineering via quorum sensing and sRNA riboregulators-interconnected
      networks and controllers.
AB  - The advent of genetic engineering has elevated our level of comprehension of
      cellular processes and functions. A natural progression of these findings is
      determining not only how these processes function within individual cells but
      also within a community. Bacterial cells monitor the conditions and
      microorganisms in their vicinity by producing, releasing and sensing chemical
      signaling molecules. When a specific cell-density threshold is reached, a quorum
      is perceived, gene expression profiles are altered and the community orchestrates
      activities that are more effective en masse. This communication mechanism, in the
      language of autoinducers (AI), is referred to as quorum sensing (QS). It has
      become increasingly evident that while scientists attempt to decipher the
      intricacies of cellular communication and quorum sensing networks, we must remain
      conscious of the broader context of how a cell may identify itself in the
      environment and how this also impacts QS. Importantly, these phenomena span time
      and length scales by several orders in magnitude. Though the revelation of small
      RNAs, as both sensing and regulatory elements participating in the quorum sensing
      cascade, has connected new pieces of the puzzle, it has also added a new tier of
      uncertainty. The complexity of quorum sensing networks makes resolution of its
      diverse mechanisms difficult. The ability to design simpler networks with
      defined, more predictable or even "modular" elements will help elucidate these
      actions. Because it embraces innovative concepts of biological design
      accommodating the many length and time scales at play, synthetic biology serves
      as one of the most promising platforms for describing QS phenomena as well as
      enabling novel implementation strategies for biotechnological application.

PMID- 22155615
TI  - Adult naked mole-rat brain retains the NMDA receptor subunit GluN2D associated
      with hypoxia tolerance in neonatal mammals.
AB  - Adult naked mole-rats show a number of systemic adaptations to a crowded
      underground habitat that is low in oxygen and high in carbon dioxide. Remarkably,
      brain slice tissue from adult naked mole-rats also is extremely tolerant to
      oxygen deprivation as indicated by maintenance of synaptic transmission under
      hypoxic conditions as well as by a delayed neuronal depolarization during anoxia.
      These characteristics resemble hypoxia tolerance in brain slices from neonates in
      a variety of mammal species. An important component of neonatal tolerance to
      hypoxia involves the subunit composition of NMDA receptors. Neonates have a high
      proportion of NMDA receptors with GluN2D subunits which are protective because
      they retard calcium entry into neurons during hypoxic episodes. Therefore, we
      hypothesized that adult naked mole-rats retain a protective, neonatal-like, NMDA
      receptor subunit profile. We used immunoblotting to assess age-related changes in
      NMDA receptor subunits in naked mole-rats and mice. The results show that adult
      naked mole-rat brain retains a much greater proportion of the hypoxia-protective
      GluN2D subunit compared to adult mice. However, age-related changes in other
      subunits (GluN2A and GluN2B) from the neonatal period to adulthood were
      comparable in mice and naked mole-rats. Hence, adult naked mole-rat brain only
      retains the neonatal NMDA receptor subunit that is associated with hypoxia
      tolerance.

PMID- 22155616
TI  - Effects of ZD7288 on firing pattern of thermosensitive neurons isolated from
      hypothalamus.
AB  - The role of the hyperpolarization-activated current (Ih) mediated by HCN channels
      in temperature sensing by the hypothalamus was addressed. In warm-sensitive
      neurons (WSNs), exposure to ZD7288, an inhibitor of Ih mediated by
      hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, decreased
      their action potential amplitudes and frequencies significantly. By contrast,
      ZD7288 had little or no effect on temperature-insensitive neurons (TINs).
      Exposure of WSNs to ZD7288 led to a significant increase in the duration of the
      inter-spike interval and a reduction of Ih irreversibly. These results suggest
      that ZD7288 have the contrasting effects on the firing patterns of WSNs versus
      TINs, which implies HCN channels play a central role in temperature sensing by
      hypothalamic neurons.

PMID- 22155617
TI  - Sexual dimorphism in endothelin-1 induced mechanical hyperalgesia in the rat.
AB  - While the onset of mechanical hyperalgesia induced by endothelin-1 was delayed in
      female rats, compared to males, the duration was much longer. Given that the
      repeated test stimulus used to assess nociceptive threshold enhances
      hyperalgesia, a phenomenon we have referred to as stimulus-induced enhancement of
      hyperalgesia, we also evaluated for sexual dimorphism in the impact of repeated
      application of the mechanical test stimulus on endothelin-1 hyperalgesia. In male
      and female rats, endothelin-1 induced hyperalgesia is already maximal at 30 min.
      At this time stimulus-induced enhancement of hyperalgesia, which is observed only
      in male rats, persisted for 3-4h. In contrast, in females, it develops only after
      a very long (15 day) delay, and is still present, without attenuation, at 45
      days. Ovariectomy eliminated these differences between male and female rats.
      These findings suggest marked, ovarian-dependent sexual dimorphism in endothelin
      1 induced mechanical hyperalgesia and its enhancement by repeated mechanical
      stimulation.

PMID- 22155618
TI  - Adult CNP::EGFP transgenic mouse shows pronounced hypomyelination and an
      increased vulnerability to cuprizone-induced demyelination.
AB  - CNP::EGFP transgenic mice, genetically engineered to express the enhanced green
      fluorescent protein (EGFP) under the control of the 2-3-cyclic nucleotide 3
      phosphodiesterase (CNPase) promoter in oligodendroglial and Schwann cells,
      constitute a very important and widely used tool for the study of oligodendrocyte
      (OLG) development and function in young mice. Our results showed that CNP::EGFP
      mice were significantly more susceptible to CPZ-induced demyelination, as
      evaluated by MBP immunostaining, oligodendroglial progenitor cell (OPC)
      recruitment and astroglial, microglial and nestin response. This enhanced
      vulnerability was a consequence of their hypomyelination. CNP::EGFP control mice
      also displayed a significant decrease in corpus callosum (CC) thickness and MBP
      immunoreactivity. Morphometric analysis further showed a significant decrease in
      the frequency of myelinated axons, myelin turns (lamellae) and g-ratio carried
      out in the optic nerve (ON) and CC of CNP::EGFP, as compared to WT mice.
      Moreover, our results showed a decrease in the number of axons of small caliber,
      concomitantly with an increase in the number of axons of bigger size with more
      and enlarged mitochondria, which suggests a high energy demand. These findings
      and those displaying that MBP+ cells and NF200 staining in the CNP::EGFP cortex
      were more sparsely distributed provide evidence of axonal loss, which was
      supported by a decreased number of NeuN+ cells in the CA3 fields of the
      hippocampus. Transgenic mice also showed an increase in microglial and astroglial
      activation, accompanied by enhanced lipid peroxidation and recruitment of
      morphologically altered OPC. Finally, CNPase protein levels proved to be lower
      than MBP in the CC, which might indicate an altered pattern in myelin proteins
      with a CNPase deficiency. Behavioral analysis of adult CNP::EGFP transgenic mice
      supported our results, as it revealed a decrease in locomotion, exploratory
      activity and motor impairment, as compared to their WT littermates. Our data
      highlight the relevance of confronting results obtained in adult CNP::EGFP mice
      with those observed in WT mice. According to our findings, CNP::EGFP
      hypomyelination might be triggered by the cellular stress induced by the high
      level of EGFP expression in mature OLG. Adult CNP::EGFP mice could be considered
      a useful tool to evaluate future therapies for demyelinating diseases such as
      multiple sclerosis (MS), since these animals present chronic demyelination with
      axonal degeneration, a characteristic of such pathologies.

PMID- 22155619
TI  - Multi-drug resistant gram negative bacilli causing early neonatal sepsis in
      India.
AB  - OBJECTIVE: To study the organisms causing early and late onset neonatal sepsis,
      with special reference to multi-drug resistant gram negative bacilli, at two
      neonatal units (one urban, one rural) in India. METHODS: Prospective surveillance
      study. RESULTS: There were 159 episodes of sepsis (81 urban and 77 rural)
      affecting 158 babies. Gram negative bacilli caused 117 infections (68%) and
      predominated at both centres in both early and late sepsis. Klebsiella pneumoniae
      was the commonest organism, causing 61 infections (38.3%). In early sepsis (0-2
      days), non-fermenting gram negative bacilli caused 42.1% of infections at the
      urban centre; there were no cases of early Group B Streptococcus sepsis. Late
      onset sepsis was mainly caused by gram negative bacilli at both centres. Multi
      drug resistance of over 80% of early-onset gram negative organisms to ampicillin,
      third generation cephalosporins and gentamicin indicates that these multi
      resistant organisms are almost certainly circulating widely in the community. The
      overall mortality from early sepsis was 27.3% (9 of 33) and from late sepsis was
      26.2% (33 of 126). Gram negative bacilli caused all deaths from early sepsis and
      87.5% of deaths from late sepsis. CONCLUSION: This study shows that multi-drug
      resistant gram negative bacilli are a major cause of early and late neonatal
      sepsis in India and are almost certainly widespread in the community.

PMID- 22155620
TI  - Understanding genetic risk for substance use and addiction: a guide for non
      geneticists.
AB  - There is considerable enthusiasm for the potential of genetics research for
      prevention and treatment of addiction and other mental disorders. As a result,
      clinicians are increasingly exposed to issues of genetics that are fairly
      complex, and for which they may not have been adequately prepared by their
      training. Studies suggest that the heritability of substance use disorders is
      approximately 0.5. Others report that family members of affected individuals
      experience a 4- to 8-fold increased risk of disorder themselves. Statements that
      addiction is "50% genetic" in origin may be taken by some to imply one's chances
      of developing the disorder, or that a lack of a positive family history confers
      immunity. In fact, such conclusions are inaccurate, their implications
      unwarranted given the true meaning of heritability. Through a review of basic
      concepts in genetic epidemiology, we attempt to demystify these estimates of risk
      and situate them within the broader context of addiction. Methods of inferring
      population genetic variance and individual familial risk are examined, with a
      focus on their practical application and limitations. An accurate
      conceptualization of addiction necessitates an approach that transcends specific
      disciplines, making a basic awareness of the perspectives of disparate
      specialties key to furthering progress in the field.

PMID- 22155621
TI  - Leptospirosis prevalence in Chinese populations in the last two decades.
AB  - Leptospirosis is a common zoonotic disease in China. From 1991 to 2010, its
      average annual incidence was 0.70 cases per 100,000 population. During these two
      decades, three major outbreaks of leptospirosis occurred due to flooding and
      heavy rainfall. Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai
      is the predominant leptospire responsible for at least 60% of Chinese cases, and
      Apodemus agrarius serves as the major animal host. Based on the differences in
      predominant leptospiral serovars, epidemic features and incidence, there are
      three leptospirosis-prevalent regions in China. However, the incidence has
      significantly decreased in the last ten years.

PMID- 22155622
TI  - A regulatory instead of an IL-17 T response predominates in Helicobacter pylori
      associated gastritis in children.
AB  - Th17 cells seem to have an important role in the efficacy of vaccines against
      Helicobacter pylori. Because children are a target group for human vaccination
      and Th17/T(reg) cells have intrinsically linked and antagonic commitments, we
      compared the gastric levels of Th17- and T(reg)-associated cytokines of children
      and adults. IL-6, IL-10 and TGF-beta1 levels and Foxp3(+) cell numbers were
      higher, but IL-1beta, IL-17A and IL-23 were lower in infected children than in
      infected adults. In conclusion T(reg) instead of Th17 cell response to H. pylori
      infection predominates in children.

PMID- 22155623
TI  - Gene expression following low dose inhalational Francisella tularensis (SchuS4)
      exposure in Balb/c mice and the potential role of the epithelium and cell
      adhesion.
AB  - Interactions between Francisella tularensis and the host are slowly being
      elucidated. Microarray technology was used to further characterise the response
      of Balb/c mice after inhalation of the virulent F. tularensis, SchuS4. The
      validated array data revealed changes in expression of 476 genes across a 96 h
      time course following infection (p <= 0.05). These data confirm down-regulation
      of the toll-like receptor pathway (TLR3, 4, 5, 7 and 8), and the induction of IFN
      gamma inducible genes (T-cell specific GTPase, beta2 microglobulin and
      interleukin 21). The overall response appears to be two staged with an initial up
      regulation of genes involved in apoptosis, TNFalpha production and antigen
      presentation. This is followed by a large alteration of expression at 96 h as the
      host succumbs to infection. A key regulatory time-point has been identified at 24
      h post challenge, where several transcriptional events may predicate the
      progression of infection; these include transcriptional regulators of
      inflammation and proteolytic pathways. Pathway analysis indicates a novel role
      for cell-cell adhesion and extracellular matrix modulation in infection.
      Transcripts representing cellular junctions, focal adhesion and adherens
      junctions changed following infection. Additionally, aspects of extracellular
      matrix remodelling have been confirmed at the protein level, suggesting an
      important role of the respiratory epithelium in host response to F. tularensis
      warranting further study.

PMID- 22155624
TI  - Magnetization distribution of magnetic vortex of amorphous FeSiB investigated by
      electron holography and computer simulation.
AB  - The three-dimensional spin structure of the magnetic vortex of FeSiB, an
      amorphous soft magnetic material, was investigated by holography observation and
      computer simulation. Magnetization distribution in the neighborhood of the vortex
      center was estimated from the phase distribution obtained by holography
      observation. To confirm this magnetization distribution, sample-tilting
      experiments were performed: when the sample was tilted with respect to the
      electron beam direction, the phase-image center was found to shift along the
      tilting axis. Finite-element computer simulation was carried out to estimate the
      amount of shifts of the phase-image center in the sample tilting from the
      experimental magnetization distributions in the no sample-tilting conditions. We
      found that the simulated shifts of the phase-image center were in good agreement
      with those in the sample-tilting experiment, thus confirming the magnetization
      distribution near the vortex center obtained by holography observation.

PMID- 22155625
TI  - Inhibitory effects of C4a on chemoattractant and secretagogue functions of the
      other anaphylatoxins via Gi protein-adenylyl cyclase inhibition pathway in mast
      cells.
AB  - A recombinant complement anaphylatoxin, C4a, inhibited chemotaxis, respiratory
      burst and histamine release in mast cell-like HMC-1 cells that were treated with
      recombinant C5a anaphylatoxin. C4a also inhibited histamine release from HMC-1
      cells that were induced by recombinant C3a. The inhibition of C5a- and C3a
      induced leukocyte reactions by C4a was recapitulated in peripheral blood CD133(+)
      cell-derived differentiated mast cells. In HMC-1 cells, C4a inhibited cytoplasmic
      Ca(2+) influx, an event that precedes anaphylatoxin-induced chemotactic and
      secretary responses. A conditioned medium of HMC-1 cells after shortly treated
      with C4a also inhibited the anaphylatoxin-induced Ca(2+) influx even after
      removal of C4a, indicating that the effect of C4a is to liberate an autocrine
      inhibitor from the mast cells. The inhibitor secretion by C4a was prevented with
      pertussis toxin or with a phosphodiesterase inhibitor. Conversely, an adenylyl
      cyclase inhibitor reproduced the effect of C4a. C4a decreased the intracellular
      cyclic AMP concentration of HMC-1 cells, indicating that C4a elicited the Gi
      protein-adenylyl cyclase inhibition pathway. Neither C4a nor the conditioned
      medium, however, inhibited Ca(2+) influx and respiratory burst in C5a- or C3a
      stimulated peripheral neutrophils, suggesting that these cells lack this
      inhibitory system. Additionally, in HMC-1 cells, C4a did not inhibit Ca(2+)
      independent, Leu72Gln-C5a-stimulated chemotactic response. In agreement with this
      finding, C4a treatment inhibited ERK1/2 phosphorylation in HMC-1 cells stimulated
      with other anaphylatoxins but did not inhibit p38MAPK phosphorylation in cells
      stimulated with Leu72Gln-C5a. Taken together, these findings suggest that the
      autocrine inhibitory effect elicited by C4a is attributed to interruption of
      Ca(2+)-dependent intracellular signaling pathway.

PMID- 22155626
TI  - Allergen induced Th17 response in the peripheral blood mononuclear cells (PBMCs)
      of patients with nasal polyposis.
AB  - BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of the nasal
      cavity and sinuses. Th17 cells have been considered to play roles in allergic
      airway diseases and various chronic inflammatory disorders. AIM OF THE STUDY:
      This study aimed to investigate the population and function of peripheral Th17
      cells in response to house dust mite extracts (HDM) allergen in NP patients, and
      evaluate the possible correlation between Th17 cells and atopy, to explore the
      role of atopy in the pathogenesis of NP. METHODS: Peripheral blood mononuclear
      cells (PBMCs) obtained from atopic NP patients, non-atopic NP patients, and
      controls were stimulated by phytohemagglutinin (PHA) or HDM plus PHA. The
      resulting frequency of Th17 cells was detected by flow cytometry and the
      expression of RORc was measured by real-time PCR. Then the concentrations of IL
      17A, INF-gamma, IL-4 and IL-5 in the supernatants were assayed by specific
      ELISAs. RESULTS: The population and function of Th17 cells in allergen stimulated
      PBMCs were significantly higher in atopic NP patients. In addition, in atopic
      group, HDM+PHA stimulation induced significant increase of Th17 population and IL
      17A production versus those in PHA stimulated ones. However, the frequency of
      Th17 cells was not correlated with Th1, Th2 cytokine productions. CONCLUSION:
      Th17 immunity is involved in the systemic immune responses to allergen in atopic
      NP and atopy may aggravate NP by stimulating the increase of Th17 population and
      IL-17A production. The mechanism of Th17 cells response to allergen may be
      regulated differently from the regulation of Th1 and Th2 immunity in NP.

PMID- 22155627
TI  - Dendrosomal curcumin significantly suppresses cancer cell proliferation in vitro
      and in vivo.
AB  - Curcumin, the main compound of spice turmeric, is one of the natural products
      that has been shown to possess effective anti-cancer properties. However, the
      absorption efficacy of curcumin is too low to make dramatic results in therapy.
      Therefore, we based the main aim of this study on improving the bioavailability
      of curcumin taking advantage of dendrosome nanoparticles; and subsequently
      evaluating in vitro and in vivo anti-tumor properties of dendrosomal curcumin. In
      vitro studies were carried out utilizing A431 and WEHI-164 cell lines and mouse
      embryonic normal fibroblasts. Our data revealed that dendrosomal curcumin not
      only exhibits a much higher bioavailability than void curcumin (P<0.05) but also
      inhibits the proliferation of cancer cells (P<0.01) in a time- and dose-dependent
      manner that could be ascribed to the induction of apoptosis. However, dendrosome
      did not indicate any toxic effect on different types of cell lines. For in vivo
      studies, BALB/c tumor-bearing mice were treated with dendrosomal curcumin, void
      curcumin, dendrosome and PBS. The results indicated that dendrosomal curcumin
      reduces significantly the tumor size in comparison with void curcumin and control
      samples (P<0.05). Furthermore, in animals treated with dendrosomal curcumin a
      longer survival was observed (P<0.01). We also found that the mice treated with
      dendrosomal curcumin, showed a significant increase in splenocyte proliferation
      and IFN-gamma production as well as a significant decrease in IL-4 production.
      This can be a proof of anti-tumor immunity caused by dendrosomal curcumin. The
      findings demonstrate that dendrosomal curcumin offers a great potential to be a
      promising anti-cancer therapeutic agent.

PMID- 22155628
TI  - Inflammation profile of four early onset Crohn patients.
AB  - Crohn disease (CD) is a multifactorial disorder affecting mainly young adults.
      Sometimes, however, it can present in the first year of life (Early onset Crohn
      disease (EOCD)) showing an unpredictable course and can often be more severe than
      at older ages. Some cases have been associated to an underlying primary
      immunodeficiency such as IL10R deficiency. We studied the functional response to
      IL-10 and the genotype of IL-10 receptor in four patients with early onset crohn
      like colitis. We found an IL10R variant, which may be associated with a decreased
      response to the cytokine in one patient. Further studies to determine its
      pathogenic effect should be performed. In addition IL-10 mediated inhibition of
      LPS-induced TNFalpha expression was measured in patient's monocytes.

PMID- 22155629
TI  - eHealth literacy among college students: a systematic review with implications
      for eHealth education.
AB  - BACKGROUND: eHealth literacy refers to the ability of individuals to seek, find,
      understand, and appraise health information from electronic resources and apply
      such knowledge to addressing or solving a health problem. While the current
      generation of college students has access to a multitude of health information on
      the Internet, access alone does not ensure that students are skilled at
      conducting Internet searches for health information. Ensuring that college
      students have the knowledge and skills necessary to conduct advanced eHealth
      searches is an important responsibility particularly for the medical education
      community. It is unclear if college students, especially those in the medical and
      health professions, need customized eHealth literacy training for finding,
      interpreting, and evaluating health- and medical-related information available on
      the Internet. OBJECTIVE: The objective of our review was to summarize and
      critically evaluate the evidence from existing research on eHealth literacy
      levels among college students between the ages of 17 and 26 years attending
      various 4-year colleges and universities located around the world. METHODS: We
      conducted a systematic literature review on numerous scholarly databases using
      various combinations of relevant search terms and Boolean operators. The records
      were screened and assessed for inclusion in the review based on preestablished
      criteria. Findings from each study that met inclusion criteria were synthesized
      and summarized into emergent themes. RESULTS: In the final review we analyzed 6
      peer-reviewed articles and 1 doctoral dissertation that satisfied the inclusion
      criteria. The number of participants in each reviewed study varied widely (from
      34 to 5030). The representativeness of the results from smaller studies is
      questionable. All studies measured knowledge and/or behaviors related to college
      student ability to locate, use, and evaluate eHealth information. These studies
      indicated that many college students lack eHealth literacy skills, suggesting
      that there is significant room for improvement in college students' ability to
      obtain and evaluate eHealth information. CONCLUSION: Although college students
      are highly connected to, and feel comfortable with, using the Internet to find
      health information, their eHealth literacy skills are generally sub par. College
      students, especially in the health and medical professions, would be well served
      to receive more customized college-level instruction that improves general
      eHealth literacy.

PMID- 22155630
TI  - Immunogenicity and safety of inactivated monovalent 2009 H1N1 influenza A vaccine
      in immunocompromised children and young adults.
AB  - BACKGROUND: Influenza vaccination is recommended for immunocompromised patients.
      METHODS: Children (6 months to 21 years) with cancer, HIV infection, or sickle
      cell disease (SCD) received 1 or 2 doses of pandemic 2009 H1N1 monovalent
      influenza vaccine (H1N1 MIV). Safety and tolerability, hemagglutination
      inhibition (HI) and microneutralization (MN) antibody titers were measured
      against 2009 H1N1 influenza A virus after each dose. Seroprotection (SP) and
      seroconversion (SC) rates were determined. RESULTS: 103 participants were
      enrolled and 99 were evaluable (39 with HIV, 37 with cancer and 23 with SCD).
      Mean age (+/-SD) was 7.9 (+/-5.4) years for cancer participants, 18.0 (+/-3.5)
      for HIV, and 13.3 (+/-4.2) for SCD. 54% were males; 65% black; and 96% had
      received seasonal influenza vaccine. HIV-infected participants had a median CD4
      count of 625 cells/mm(3) (range, 140-1260). 46% had an undetectable HIV viral
      load and 41% were perinatally infected. No participant had vaccine-related
      serious adverse events. None developed influenza A proven illness during the 6
      months after the vaccine. Local injection reactions were reported in 29% and
      systemic reactions in 42% after the first dose of vaccine. SC and SP were
      achieved after the last dose in 48% and 52%, respectively, of participants with
      leukemia or lymphoma, 50% and 75% of participants with solid tumors, 63% and 92%
      of HIV-infected participants, and 74% and 100% of participants with SCD.
      CONCLUSION: H1N1 MIV was safe and well tolerated. H1N1 MIV resulted in an
      adequate immune response in children with SCD. It was only modestly immunogenic
      in cancer or HIV participants.

PMID- 22155631
TI  - Vascular functioning and the water balance of ripening kiwifruit (Actinidia
      chinensis) berries.
AB  - Indirect evidence suggests that water supply to fleshy fruits during the final
      stages of development occurs through the phloem, with the xylem providing little
      water, or acting as a pathway for water loss back to the plant. This inference
      was tested by examining the water balance and vascular functioning of ripening
      kiwifruit berries (Actinidia chinensis var. chinensis 'Hort16A') exhibiting a pre
      harvest 'shrivel' disorder in California, and normal development in New Zealand.
      Dye labelling and mass balance experiments indicated that the xylem and phloem
      were both functional and contributed approximately equally to the fruit water
      supply during this stage of development. The modelled fruit water balance was
      dominated by transpiration, with net water loss under high vapour pressure
      deficit (D(a)) conditions in California, but a net gain under cooler New Zealand
      conditions. Direct measurement of pedicel sap flow under controlled conditions
      confirmed inward flows in both the phloem and xylem under conditions of both low
      and high D(a). Phloem flows were required for growth, with gradual recovery after
      a step increase in D(a). Xylem flows alone were unable to support growth, but did
      supply transpiration and were responsive to D(a)-induced pressure fluctuations.
      The results suggest that the shrivel disorder was a consequence of a high fruit
      transpiration rate, and that the perception of complete loss or reversal of
      inward xylem flows in ripening fruits should be re-examined.

PMID- 22155633
TI  - Inhibiting effect of alpha(s1)-casein on Abeta(1-40) fibrillogenesis.
AB  - BACKGROUND: alpha(s1)-Casein is one of the four types of caseins, the largest
      protein component of bovine milk. The lack of a compact folded conformation and
      the capability to form micelles suggest a relationship of alpha(s1)-casein with
      the class of the intrinsically disordered (or natively unfolded) proteins. These
      proteins are known to exert a stabilizing activity on biomolecules through
      specific interaction with hydrophobic surfaces. In the present work we focused on
      the effect of alpha(s1)-casein on the fibrillogenesis of 1-40 beta-amyloid
      peptide, involved in Alzheimer's disease. METHODS: The aggregation kinetics of
      beta-peptide in presence and absence of alpha(s1)-casein was followed under shear
      at 37 degrees C by recording the Thioflavine fluorescence, usually taken as an
      indicator of fibers formation. Measurements of Static and Dynamic Light
      Scattering, Circular Dichroism, and AFM imaging were done to reveal the details
      of alpha(s1)-casein-Abeta(1-40) interaction. RESULTS AND DISCUSSIONS: alpha(s1)
      Casein addition sizably increases the lag-time of the nucleation phase and slows
      down the entire fibrillization process. alpha(s1)-Casein sequesters the amyloid
      peptide on its surface thus exerting a chaperone-like activity by means a
      colloidal inhibition mechanism. GENERAL SIGNIFICANCE: Insights on the working
      mechanism of natural chaperones in preventing or controlling the amyloid
      aggregation.

PMID- 22155632
TI  - Arabidopsis thaliana DOF6 negatively affects germination in non-after-ripened
      seeds and interacts with TCP14.
AB  - Seed dormancy prevents seeds from germinating under environmental conditions
      unfavourable for plant growth and development and constitutes an evolutionary
      advantage. Dry storage, also known as after-ripening, gradually decreases seed
      dormancy by mechanisms not well understood. An Arabidopsis thaliana DOF
      transcription factor gene (DOF6) affecting seed germination has been
      characterized. The transcript levels of this gene accumulate in dry seeds and
      decay gradually during after-ripening and also upon seed imbibition. While
      constitutive over-expression of DOF6 produced aberrant growth and sterility in
      the plant, its over-expression induced upon seed imbibition triggered delayed
      germination, abscisic acid (ABA)-hypersensitive phenotypes and increased
      expression of the ABA biosynthetic gene ABA1 and ABA-related stress genes. Wild
      type germination and gene expression were gradually restored during seed after
      ripening, despite of DOF6-induced over-expression. DOF6 was found to interact in
      a yeast two-hybrid system and in planta with TCP14, a previously described
      positive regulator of seed germination. The expression of ABA1 and ABA-related
      stress genes was also enhanced in tcp14 knock-out mutants. Taken together, these
      results indicate that DOF6 negatively affects seed germination and opposes TCP14
      function in the regulation of a specific set of ABA-related genes.

PMID- 22155634
TI  - Influence of the pathogenic mutations T188K/R/A on the structural stability and
      misfolding of human prion protein: insight from molecular dynamics simulations.
AB  - BACKGROUND: Prion diseases are associated with a conformational switch for PrP
      from PrP(C) to PrP(Sc). Many genetic mutations are linked with prion diseases,
      such as mutations T188K/R/A with fCJD. SCOPE OF REVIEW: MD simulations for the WT
      PrP and its mutants were performed to explore the underlying dynamic effects of
      T188 mutations on human PrP. Although the globular domains are fairly conserved,
      the three mutations have diverse effects on the dynamics properties of PrP,
      including the shift of H1, the elongation of native beta-sheet and the conversion
      of S2-H2 loop to a 3(10) helix. MAJOR CONCLUSIONS: Our present study indicates
      that the three mutants for PrP may undergo different pathogenic mechanisms and
      the realistic atomistic simulations can provide insights into the effects of
      disease-associated mutations on PrP dynamics and stability, which can enhance our
      understanding of how mutations induce the conversion from PrP(C) to PrP(Sc).
      General significance Our present study helps to understand the effects of
      T188K/R/A mutations on human PrP: despite the three pathogenic mutations almost
      do not alter the native structure of PrP, but perturb its stability. This
      instability may further modulate the oligomerization pathways and determine the
      features of the PrP(Sc) assemblies.

PMID- 22155635
TI  - 20-hydroxyecdysone and juvenile hormone analog prevent precocious metamorphosis
      in recessive trimolter mutants of Bombyx mori.
AB  - The trimolter mutants of Bombyx mori have four instead of five larval instars of
      normal tetramolters. Here, we show that the tetramolter was induced in the
      recessive trimolter European No.7 mutant (rt-E7) by application of either the
      juvenile hormone analog (JHA) or 20-hydroxyecdysone (20E). However, treatments
      with JHA or 20E did not change the number of larval instars of the dominant
      trimolter Si Chuan mutant (DT-SC). Kruppel-homolog 1 (Kr-h1) is an early JH
      response gene that mediates the anti-metamorphic action of JH. In the wing disc
      of tetramolter B. mori, Kr-h1 RNAs decreased shortly after ecdysis to the fifth
      instar, while pupal specifier gene, Broad Complex Z1 (BR-Z1) RNAs slightly
      increased and coincided with the onset of metamorphic competence of wing discs.
      Analysis of the developmental profile of Kr-h1 in the wing disc of rt-E7 showed
      that its transcript slightly increased from 12 to 24 h and gradually decreased
      between 24 and 72 h in the fourth (last) larval instar, while Kr-h1 mRNA
      decreased rapidly between 12 and 72 h in DT-SC. In addition, the expression of BR
      Z1 in DT-SC during the early fourth (last) larval instar is relatively higher
      than that in rt-E7. These results indicated that the occurrence of pupal
      commitment of the wing disc in DT-SC was much earlier than that in rt-E7. In the
      early fourth larval instar of rt-E7, feeding on 20E or treatments with exogenous
      JHA caused up-regulation of Kr-h1, suppressed premature induction of BR-Z1, and
      then induced an additional larval instar. By contrast, in DT-SC mutant, since
      pupal commitment immediately occurred after third ecdysis, precocious
      metamorphosis was not successfully rescued. The results suggest that Kr-h1 and BR
      Z1 involved in the prevention of precocious metamorphosis in recessive trimolter
      mutants by application of 20E and JHA. The result indicated that Kr-h1 and BR-Z1
      expression reflected larval-pupal transition of the recessive trimolter of B.
      mori.

PMID- 22155638
TI  - Characterisation and expression analysis of B-cell activating factor (BAFF) in
      spiny dogfish (Squalus acanthias): cartilaginous fish BAFF has a unique extra
      exon that may impact receptor binding.
AB  - B-cell activating factor (BAFF), also known as tumour necrosis factor (TNF)
      ligand superfamily member 13B, is an important immune regulator with critical
      roles in B-cell survival, proliferation, differentiation and immunoglobulin
      secretion. A BAFF gene has been cloned from spiny dogfish (Squalus acanthias) and
      its expression studied. The dogfish BAFF encodes for an anchored type-II
      transmembrane protein of 288 aa with a putative furin protease cleavage site and
      TNF family signature as seen in BAFFs from other species. The identity of dogfish
      BAFF has also been confirmed by conserved cysteine residues, and phylogenetic
      tree analysis. The dogfish BAFF gene has an extra exon not seen in teleost fish,
      birds and mammals that encodes for 29 aa and may impact on receptor binding. The
      dogfish BAFF is highly expressed in immune tissues, such as spleen, and is up
      regulated by PWM in peripheral blood leucocytes, suggesting a potentially
      important role in the immune system.

PMID- 22155637
TI  - Peyer's patch dendritic cells sample antigens by extending dendrites through M
      cell-specific transcellular pores.
AB  - BACKGROUND & AIMS: Peyer's patches (PPs) of the small intestine are antigen
      sampling and inductive sites that help establish mucosal immunity. Luminal
      antigens are transported from the mucosal surface of PPs to the subepithelial
      dome (SED), through the specialized epithelial M cells of the follicle-associated
      epithelium. Among the SED resident dendritic cells (DCs), which are situated
      ideally for taking up these antigens, some express high levels of lysozyme
      (LysoDC) and have strong phagocytic activity. We investigated the mechanisms by
      which LysoDCs capture luminal antigens in vivo. METHODS: We performed 2-photon
      microscopy on explants of PPs from mice in which the enhanced green fluorescent
      protein gene was inserted into the lysozyme M locus (lys-EGFP mice), allowing
      fluorescence detection of LysoDC. RESULTS: LysoDC extended dendrites through M
      cell-specific transcellular pores to the gut lumen. The M-cell adhesion molecules
      junctional adhesion molecule-A and epithelial cell adhesion molecule were
      recruited to sites of transcellular migration. Transcellular dendrites scanned
      the M-cell apical surface and the gut luminal content; they were able to take
      pathogenic bacteria and inert particles in the lumen before retracting back to
      the SED. CONCLUSIONS: We describe an antigen sampling mechanism that occurs in
      PPs and involves cooperation between M cells of the follicle-associated
      epithelium and DCs of the subepithelial dome. This process might be developed to
      target vaccines to the mucosa.

PMID- 22155636
TI  - Dysregulation of Wnt/beta-catenin signaling in gastrointestinal cancers.
AB  - Aberrant Wnt/beta-catenin signaling is widely implicated in numerous
      malignancies, including cancers of the gastrointestinal tract. Dysregulation of
      signaling is traditionally attributed to mutations in Axin, adenomatous polyposis
      coli, and beta-catenin that lead to constitutive hyperactivation of the pathway.
      However, Wnt/beta-catenin signaling is also modulated through various other
      mechanisms in cancer, including cross talk with other altered signaling pathways.
      A more complex view of Wnt/beta-catenin signaling and its role in
      gastrointestinal cancers is now emerging as divergent phenotypic outcomes are
      found to be dictated by temporospatial context and relative levels of pathway
      activation. This review summarizes the dysregulation of Wnt/beta-catenin
      signaling in colorectal carcinoma, hepatocellular carcinoma, and pancreatic
      ductal adenocarcinoma, with particular emphasis on the latter two. We conclude by
      addressing some of the major challenges faced in attempting to target the pathway
      in the clinic.

PMID- 22155639
TI  - Acetylation-dependent regulation of mitochondrial ALDH2 activation by SIRT3
      mediates acute ethanol-induced eNOS activation.
AB  - Moderate alcohol consumption has beneficial effects on endothelial nitric-oxide
      synthase (eNOS) activation, which can engender an array of anti-atherogenic
      actions. Here we show that in human aortic endothelial cells (HAECs), rapid
      activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) mediates ethanol
      induced eNOS activation by preventing reactive oxygen species (ROS) accumulation.
      Furthermore, activation of ALDH2 by ethanol is due to its hyperacetylation by
      SIRT3 inactivation. These data suggest that ethanol-induced eNOS activation in
      HAECs may be dependent on ALDH2 hyperacetylation by SIRT3 inactivation.

PMID- 22155640
TI  - The yeast metacaspase is implicated in oxidative stress response in frataxin
      deficient cells.
AB  - Friedreich ataxia is the most common recessive neurodegenerative disease and is
      caused by reduced expression of mitochondrial frataxin. Frataxin depletion causes
      impairment in iron-sulfur cluster and heme biosynthesis, disruption of iron
      homeostasis and hypersensitivity to oxidants. Currently no pharmacological
      treatment blocks disease progression, although antioxidant therapies proved to
      benefit patients. We show that sensitivity of yeast frataxin-deficient cells to
      hydrogen peroxide is partially mediated by the metacaspase. Metacaspase deletion
      in frataxin-deficient cells results in recovery of antioxidant capacity and heme
      synthesis. In addition, our results suggest that metacaspase is associated with
      mitochondrial respiration, intracellular redox control and genomic stability.

PMID- 22155641
TI  - Hive plots--rational approach to visualizing networks.
AB  - Networks are typically visualized with force-based or spectral layouts. These
      algorithms lack reproducibility and perceptual uniformity because they do not use
      a node coordinate system. The layouts can be difficult to interpret and are
      unsuitable for assessing differences in networks. To address these issues, we
      introduce hive plots (http://www.hiveplot.com) for generating informative,
      quantitative and comparable network layouts. Hive plots depict network structure
      transparently, are simple to understand and can be easily tuned to identify
      patterns of interest. The method is computationally straightforward, scales well
      and is amenable to a plugin for existing tools.

PMID- 22155642
TI  - Transmembrane domains interactions within the membrane milieu: principles,
      advances and challenges.
AB  - Protein-protein interactions within the membrane are involved in many vital
      cellular processes. Consequently, deficient oligomerization is associated with
      known diseases. The interactions can be partially or fully mediated by
      transmembrane domains (TMD). However, in contrast to soluble regions, our
      knowledge of the factors that control oligomerization and recognition between the
      membrane-embedded domains is very limited. Due to the unique chemical and
      physical properties of the membrane environment, rules that apply to interactions
      between soluble segments are not necessarily valid within the membrane. This
      review summarizes our knowledge on the sequences mediating TMD-TMD interactions
      which include conserved motifs such as the GxxxG, QxxS, glycine and leucine
      zippers, and others. The review discusses the specific role of polar, charged and
      aromatic amino acids in the interface of the interacting TMD helices. Strategies
      to determine the strength, dynamics and specificities of these interactions by
      experimental (ToxR, TOXCAT, GALLEX and FRET) or various computational approaches
      (molecular dynamic simulation and bioinformatics) are summarized. Importantly,
      the contribution of the membrane environment to the TMD-TMD interaction is also
      presented. Studies utilizing exogenously added TMD peptides have been shown to
      influence in vivo the dimerization of intact membrane proteins involved in
      various diseases. The chirality independent TMD-TMD interactions allows for the
      design of novel short d- and l-amino acids containing TMD peptides with advanced
      properties. Overall these studies shed light on the role of specific amino acids
      in mediating the assembly of the TMDs within the membrane environment and their
      contribution to protein function. This article is part of a Special Issue
      entitled: Protein Folding in Membranes.

PMID- 22155643
TI  - Interaction of alpha-synuclein with vesicles that mimic mitochondrial membranes.
AB  - alpha-Synuclein, an intrinsically-disordered protein associated with Parkinson's
      disease, interacts with mitochondria, but the details of this interaction are
      unknown. We probed the interaction of alpha-synuclein and its A30P variant with
      lipid vesicles by using fluorescence anisotropy and (19)F nuclear magnetic
      resonance. Both proteins interact strongly with large unilamellar vesicles whose
      composition is similar to that of the inner mitochondrial membrane, which
      contains cardiolipin. However, the proteins have no affinity for vesicles
      mimicking the outer mitochondrial membrane, which lacks cardiolipin. The (19)F
      data show that the interaction involves alpha-synuclein's N-terminal region.
      These data indicate that the middle of the N-terminal region, which contains the
      KAKEGVVAAAE repeats, is involved in binding, probably via electrostatic
      interactions between the lysines and cardiolipin. We also found that the strength
      of alpha-synuclein binding depends on the nature of the cardiolipin acyl side
      chains. Eliminating one double bond increases affinity, while complete saturation
      dramatically decreases affinity. Increasing the temperature increases the binding
      of wild-type, but not the A30P variant. The data are interpreted in terms of the
      properties of the protein, cardiolipin demixing within the vesicles upon binding
      of alpha-synuclein, and packing density. The results advance our understanding of
      alpha-synuclein's interaction with mitochondrial membranes.

PMID- 22155644
TI  - Regulation of plasma membrane Ca(2+)-ATPase activity by acetylated tubulin:
      influence of the lipid environment.
AB  - We demonstrated previously that acetylated tubulin inhibits plasma membrane
      Ca(2+)-ATPase (PMCA) activity in plasma membrane vesicles (PMVs) of rat brain
      through a reversible interaction. Dissociation of the PMCA/tubulin complex leads
      to restoration of ATPase activity. We now report that, when the enzyme is
      reconstituted in phosphatidylcholine vesicles containing acidic or neutral
      lipids, tubulin not only loses its inhibitory effect but is also capable of
      activating PMCA. This alteration of the PMCA-inhibitory effect of tubulin was
      dependent on concentrations of both lipids and tubulin. Tubulin (300MUg/ml) in
      combination with acidic lipids at concentrations >10%, increased PMCA activity up
      to 27-fold. The neutral lipid diacylglycerol (DAG), in combination with 50MUg/ml
      tubulin, increased PMCA activity >12-fold, whereas tubulin alone at high
      concentration (>=300MUg/ml) produced only 80% increase. When DAG was generated in
      situ by phospholipase C incubation of PMVs pre-treated with exogenous tubulin,
      the inhibitory effect of tubulin on PMCA activity (ATP hydrolysis, and Ca(2+)
      transport within vesicles) was reversed. These findings indicate that PMCA is
      activated independently of surrounding lipid composition at low tubulin
      concentrations (<50MUg/ml), whereas PMCA is activated mainly by reconstitution in
      acidic lipids at high tubulin concentrations. Regulation of PMCA activity by
      tubulin is thus dependent on both membrane lipid composition and tubulin
      concentration.

PMID- 22155645
TI  - Cardiovascular risk in androgen suppression: underappreciated, under-researched
      and unresolved.

PMID- 22155646
TI  - What makes a good drug target?
AB  - Novel therapeutics in areas with a high unmet medical need are based on
      innovative drug targets. Although 'biologicals' have enlarged the space of
      druggable molecules, the number of appropriate drug targets is still limited.
      Discovering and assessing the potential therapeutic benefit of a drug target is
      based not only on experimental, mechanistic and pharmacological studies but also
      on a theoretical molecular druggability assessment, an early evaluation of
      potential side effects and considerations regarding opportunities for
      commercialization. This article defines key properties of a good drug target from
      the perspective of a pharmaceutical company.

PMID- 22155647
TI  - An outbreak of schistosomiasis in travellers returning from endemic areas: the
      importance of rigorous tracing in peer groups exposed to risk of infection.
AB  - BACKGROUND: Each year, schools across Scotland send their students on exchange
      programmes to Malawi. Between 2005 and 2009, 22.8% of Scotland's new cases of
      schistosomiasis were from freshwater exposure in Malawi, with 41.5% diagnosed in
      15-24 year olds. In January 2011, a 17-year-old male presented to our urology
      department with visible haematuria following freshwater exposure during a school
      trip to Malawi. He was subsequently diagnosed with urinary schistosomiasis.
      METHODS: The potential involvement of other individuals from the trip prompted
      further public health enquiry. The school, public health department and education
      authorities were notified promptly and all individuals potentially exposed to
      Schistosoma haematobium were invited for screening. RESULTS: All 21 participants
      of the exchange programme underwent serological screening. Thirteen tested
      positive for Schistosoma infection. Only two individuals displayed symptoms of
      schistosomiasis; the other 11 were asymptomatic. CONCLUSIONS: Infection rates,
      even following a limited exposure to S. haematobium, are high. The majority of
      seropositive cases may never have symptoms. Therefore, a history of foreign
      travel to endemic schistosomiasis areas should be sought from any young person
      presenting with visible heamaturia and appropriate tests instigated. Schools
      should adopt policies forbidding activities involving freshwater exposure in
      Malawi. Effective public health measures must be set in place to trace and treat
      any other possible cases of exposure.

PMID- 22155648
TI  - Production of recombinant Rhizopus oryzae lipase by the yeast Yarrowia lipolytica
      results in increased enzymatic thermostability.
AB  - The gene encoding Rhizopus oryzae lipase (ROL) was expressed in the non
      conventional yeast Yarrowia lipolytica under the control of the strong inducible
      XPR2 gene promoter. The effects of three different preprosequence variants were
      examined: a preprosequence of the Y. lipolytica alkaline extracellular protease
      (AEP) encoded by XPR2, the native preprosequence of ROL, and a hybrid variant of
      the presequence of AEP and the prosequence of ROL. Lipase production was highest
      (7.6 U/mL) with the hybrid prepropeptide. The recombinant protein was purified by
      ion-exchange chromatography. The ROL included 28 amino acids of the C-terminal
      region of the prosequence, indicating that proteolytic cleavage occurred below
      the KR site through the activity of the Kex2-like endoprotease. The optimum
      temperature for recombinant lipase activity was between 30 and 40  degrees C, and
      the optimum pH was 7.5. The enzyme was shown not to be glycosylated. Furthermore,
      recombinant ROL exhibited greater thermostability than previously reported, with
      the enzyme retaining 64% of its hydrolytic activity after 30 min of incubation at
      55  degrees C.

PMID- 22155649
TI  - Determinants of engagement in face-to-face and online patient support groups.
AB  - BACKGROUND: Although peer-to-peer contact might empower patients in various ways,
      studies show that only a few patients actually engage in support groups.
      OBJECTIVE: The objective of our study was to explore factors that facilitate or
      impede engagement in face-to-face and online peer support, using the theory of
      planned behavior (TPB). METHODS: A questionnaire was completed by 679 patients
      being treated for arthritis, breast cancer, or fibromyalgia at two Dutch regional
      hospitals. RESULTS: Our results showed that only a minority of the patients
      engaged in organized forms of peer support. In total 10% (65/679) of the
      respondents had engaged in face-to-face meetings for patients in the past year.
      Only 4% (30/679) of the respondents had contact with peers via the Internet in
      the past year. Patients were more positive about face-to-face peer support than
      about online peer support (P < .001). In accordance with the TPB, having a more
      positive attitude (P < .01) and feeling more supported by people in the social
      environment (P < .001) increased the intention to participate in both kinds of
      peer support. In addition, perceived behavioral control (P = .01) influenced the
      intention to participate in online peer support. Nevertheless, the intention to
      engage in face-to-face and online peer support was only modestly predicted by the
      TPB variables (R(2) = .33 for face-to-face contact and R(2) = .26 for online
      contact). CONCLUSION: Although Health 2.0 Internet technology has significantly
      increased opportunities for having contact with fellow patients, only a minority
      seem to be interested in organized forms of peer contact (either online or face
      to-face). Patients seem somewhat more positive about face-to-face contact than
      about online contact.

PMID- 22155651
TI  - Cholinergic and GABAergic receptor functional deficit in the hippocampus of
      insulin-induced hypoglycemic and streptozotocin-induced diabetic rats.
AB  - Neurotransmitter receptor functional regulation plays an important role in
      controlling the excitability and responsiveness of hippocampal neurons.
      Deregulation of its function is associated with seizure generation, motor
      deficits, and memory impairment. In the present study we investigated the changes
      in hippocampal cholinergic and GABA receptor binding and gene expression in
      insulin-induced hypoglycemic and streptozotocin-induced diabetic rats. Expression
      of cholinergic enzymes; acetylcholine esterase (AChE) and choline
      acetyltransferase (ChAT) upregulated and downregulated, respectively, in diabetic
      group, which was further exacerbated by hypoglycemia. Total muscarinic receptor,
      muscarinic M1, and GABA maximal binding (B(max)) significantly decreased in
      hypoglycemic and diabetic rats. In hypoglycemic group, the B(max) showed further
      decline compared with diabetes. Muscarinic M3 receptor B(max) and gene expression
      upregulated in hypoglycemic and diabetic group. Alpha7 nicotinic acetylcholine
      receptor (alpha7 nAChR) expression significantly downregulated in hypoglycemic
      and diabetic rats. Gene expression of glutamate decarboxylase (GAD), GABAAalpha1,
      and GABAB in hypoglycemic and diabetic rats downregulated, with more significant
      decrease in hypoglycemic group. Present findings show altered cholinergic,
      muscarinic, nicotinic receptor expression and thereby function. Decreased GABA
      receptor expression is associated with decline in GABAergic neurotransmission.
      Thus cholinergic receptor dysfunction and decreased GABAergic neuroprotective
      inhibitory function in the hippocampus of hypoglycemic and diabetic rats account
      for the increased vulnerability of hippocampus predisposing to neuronal damage,
      which is suggested to contribute to cognitive impairment and memory deficit
      reported in hypoglycemia and diabetes. Also, recurrent hypoglycemia in diabetes
      exacerbates the hippocampal dysfunction induced by diabetes, which has clinical
      significance in diabetes therapy.

PMID- 22155652
TI  - The new P2Y-like receptor G protein-coupled receptor 17 mediates acute neuronal
      injury and late microgliosis after focal cerebral ischemia in rats.
AB  - G protein-coupled receptor 17 (GPR17), the new P2Y-like receptor, is
      phylogenetically related to the P2Y and cysteinyl leukotriene receptors, and
      responds to both uracil nucleotides and cysteinyl leukotrienes. GPR17 has been
      proposed to be a damage sensor in ischemic stroke; however, its role in brain
      inflammation needs further detailed investigation. Here, we extended previous
      studies on the spatiotemporal profiles of GPR17 expression and localization, and
      their implications for brain injury after focal cerebral ischemia. We found that
      in the ischemic core, GPR17 mRNA and protein levels were upregulated at both 12
      24 h and 7-14 days, but in the boundary zone the levels increased 7-14 days after
      reperfusion. The spatiotemporal pattern of GPR17 expression well matched the
      acute and late (subacute/chronic) responses in the ischemic brain. According to
      previous findings, in the acute phase, after ischemia (24 h), upregulated GPR17
      was localized in injured neurons in the ischemic core and in a few microglia in
      the ischemic core and boundary zone. In the late phase (14 days), it was
      localized in microglia, especially in activated (ED1-positive) microglia in the
      ischemic core, but weakly in most microglia in the boundary zone. No GPR17 was
      detectable in astrocytes. GPR17 knockdown by a small interfering RNA attenuated
      the neurological dysfunction, infarction, and neuron loss at 24 h, and brain
      atrophy, neuron loss, and microglial activation at 14 days after reperfusion.
      Thus, GPR17 might mediate acute neuronal injury and late microgliosis after focal
      cerebral ischemia.

PMID- 22155653
TI  - Increased cholecystokinin labeling in the hippocampus of a mouse model of
      epilepsy maps to spines and glutamatergic terminals.
AB  - The neuropeptide cholecystokinin (CCK) is abundant in the CNS and is expressed in
      a subset of inhibitory interneurons, particularly in their axon terminals. The
      expression profile of CCK undergoes numerous changes in several models of
      temporal lobe epilepsy. Previous studies in the pilocarpine model of epilepsy
      have shown that CCK immunohistochemical labeling is substantially reduced in
      several regions of the hippocampal formation, consistent with decreased CCK
      expression as well as selective neuronal degeneration. However, in a mouse
      pilocarpine model of recurrent seizures, increases in CCK-labeling also occur and
      are especially striking in the hippocampal dendritic layers of strata oriens and
      radiatum. Characterizing these changes and determining the cellular basis of the
      increased labeling were the major goals of the current study. One possibility was
      that the enhanced CCK labeling could be associated with an increase in GABAergic
      terminals within these regions. However, in contrast to the marked increase in
      CCK-labeled structures, labeling of GABAergic axon terminals was decreased in the
      dendritic layers. Likewise, cannabinoid receptor 1-labeled axon terminals, many
      of which are CCK-containing GABAergic terminals, were also decreased. These
      findings suggested that the enhanced CCK labeling was not due to an increase in
      GABAergic axon terminals. The subcellular localization of CCK immunoreactivity
      was then examined using electron microscopy, and the identities of the structures
      that formed synaptic contacts were determined. In pilocarpine-treated mice, CCK
      was observed in dendritic spines and these were proportionally increased relative
      to controls, whereas the proportion of CCK-labeled terminals forming symmetric
      synapses was decreased. In addition, CCK-positive axon terminals forming
      asymmetric synapses were readily observed in these mice. Double labeling with
      vesicular glutamate transporter 1 and CCK revealed colocalization in numerous
      terminals forming asymmetric synapses, confirming the glutamatergic identity of
      these terminals. These data raise the possibility that expression of CCK is
      increased in hippocampal pyramidal cells in mice with recurrent, spontaneous
      seizures.

PMID- 22155654
TI  - Differential ascending projections of temporomandibular joint-responsive
      brainstem neurons to periaqueductal gray and posterior thalamus of male and
      female rats.
AB  - Several craniofacial pain conditions, including temporomandibular joint disorders
      (TMJDs), are more prevalent in women than men. The basis for sex differences in
      deep craniofacial pain is not known. The present study compared the magnitude of
      ascending projections from temporomandibular joint (TMJ)-responsive neurons in
      trigeminal brainstem with the ventrolateral periaqueductal gray (vlPAG) or
      posterior nucleus of the thalamus (Po) in males and female rats. Fluorogold (FG)
      was injected into vlPAG or Po, and TMJ-responsive neurons were identified by Fos
      like immunoreactivity (Fos-LI) after mustard oil injection. TMJ-evoked Fos-LI was
      similar in males and females; however, significant differences in cell counts
      were seen for FG single-labeled and Fos/FG double-labeled neurons in trigeminal
      brainstem. After vlPAG injections, the number of FG-labeled neurons in trigeminal
      subnucleus interpolaris (Vi), ventral interpolaris/caudalis transition (vl
      Vi/Vc), and dorsal paratrigeminal region (dPa5) was greater in females than
      males. The percentage of Fos/FG double-labeled neurons in vl-Vi/Vc and dPa5 after
      vlPAG injection also was greater in females than males. In contrast, after Po
      injections, males displayed a greater number of FG-labeled neurons in superficial
      laminae (Lam I/II) of trigeminal subnucleus caudalis (Vc) and upper cervical
      spinal cord (C(1-2)) and deeper laminae (Lam III/V) at C(1-2) than females. The
      percentage of Fos/FG double-labeled neurons in Lam I/II of Vc after Po injection
      also was greater in males than females. These data revealed significant sex
      differences in ascending projections from TMJ-responsive neurons in trigeminal
      brainstem. Such differences may influence the ability of males and females to
      recruit autonomic reflexes and endogenous pain control circuits relevant for TMJ
      nociception.

PMID- 22155655
TI  - Spatial memory is improved by aerobic and resistance exercise through divergent
      molecular mechanisms.
AB  - A growing body of scientific evidence indicates that exercise has a positive
      impact on human health, including neurological health. Aerobic exercise, which is
      supposed to enhance cardiovascular functions and metabolism, also induces
      neurotrophic factors that affect hippocampal neurons, thereby improving spatial
      learning and memory. Alternatively, little is known about the effect of
      resistance exercise on hippocampus-dependent memory, although this type of
      exercise is increasingly recommended to improve muscle strength and bone density
      and to prevent age-related disabilities. Therefore, we evaluated the effects of
      resistance training on spatial memory and the signaling pathways of brain-derived
      neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), comparing
      these effects with those of aerobic exercise. Adult male Wistar rats underwent 8
      weeks of aerobic training on a treadmill (AERO group) or resistance training on a
      vertical ladder (RES group). Control and sham groups were also included. After
      the training period, both AERO and RES groups showed improved learning and
      spatial memory in a similar manner. However, both groups presented distinct
      signaling pathways. Although the AERO group showed increased level of IGF-1,
      BDNF, TrkB, and beta-CaMKII (calcium/calmodulin-dependent kinase II) in the
      hippocampus, the RES group showed an induction of peripheral and hippocampal IGF
      1 with concomitant activation of receptor for IGF-1 (IGF-1R) and AKT in the
      hippocampus. These distinct pathways culminated in an increase of synapsin 1 and
      synaptophysin expression in both groups. These findings demonstrated that both
      aerobic and resistance exercise can employ divergent molecular mechanisms but
      achieve similar results on learning and spatial memory.

PMID- 22155656
TI  - Sphingosine kinase 1 knockdown reduces insulin synthesis and secretion in a rat
      insulinoma cell line.
AB  - To evaluate the role of sphingosine kinase 1 (SphK1) in insulin secretion, we
      used stable transfection to knock down the expression of the Sphk1 gene in the
      rat insulinoma INS-1 832/13 cell line. Cell lines with lowered Sphk1 mRNA
      expression and SphK1 enzyme activity (SK11 and SK14) exhibited lowered glucose-
      and 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) plus glutamine
      stimulated insulin release and low insulin content associated with decreases in
      the mRNA of the insulin 1 gene. Overexpression of the rat or human Sphk1 cDNA
      restored insulin secretion and total insulin content in the SK11 cell line, but
      not in the SK14 cell line. The Sphk1 cDNA-transfected SK14 cell line expressed
      significantly less SphK1 activity than the Sphk1 cDNA-transfected SK11 cells
      suggesting that the shRNA targeting SK14 was more effective in silencing the
      exogenous rat Sphk1 mRNA. The results indicate that SphK1 activity is important
      for insulin synthesis and secretion.

PMID- 22155657
TI  - Uptake and disposition of 1,1-difluoroethane (HFC-152a) in humans.
AB  - The aim of this study was to determine the toxicokinetics of inhaled 1,1
      difluoroethane (HFC-152a) in humans. Healthy volunteers were exposed to 0, 200 or
      1000 ppm 1,1-difluoroethane for 2h at light exercise in an exposure chamber.
      Capillary blood, urine and exhaled air were sampled up to 22 h post-exposure and
      analyzed for 1,1-difluoroethane. Fluoride and other potential metabolites were
      analyzed in urine. Symptoms of irritation and central nervous system effects were
      rated and inflammatory markers were analyzed in blood. Within a few minutes of
      exposure to 200 and 1000 ppm, 1,1-difluoroethane increased rapidly in blood and
      reached average levels of 7.4 and 34.3 MUM, respectively. The post-exposure
      decreases in blood were fast and parallel to those in exhaled air. The observed
      time courses in blood and breath agreed well with those obtained with the PBPK
      model. The PBPK simulations indicate a net uptake during exposure to 1000 ppm of
      6.6 mmol (6.7%) which corresponds to the amount exhaled post-exposure. About 20
      MUmol excess fluoride (0.013% of inhaled 1,1-difluoroethane on a molar basis) was
      excreted in urine after exposure to 1000 ppm, compared to control. No fluorine
      containing metabolites were detected in urine. Symptom ratings and changes in
      inflammatory markers revealed no exposure-related effects.

PMID- 22155658
TI  - Induction of apoptosis and cell cycle arrest by Bis (2-ethylhexyl) phthalate
      produced by marine Bacillus pumilus MB 40.
AB  - Marine microorganisms represent a potential source for the production of
      biomedically useful compounds active against inflammation, cancer, diabetes, etc.
      Marine Bacillus pumilus MB 40 (GenBank accession no. HQ705771) isolated from deep
      sea water column (1000m depth) near Andaman and Nicobar islands produced a
      bioactive lead, Bis (2-ethylhexyl) phthalate (BEHP) with a molecular formula of
      C(6)H(4)(CO(2)C(8)H(17))(2) and a molecular ion at m/z 391 (M(+)). Anti
      proliferative effect of the isolated compound was examined by MTT assay in human
      erythroleukemic K562 cells and the IC(50) of BEHP was found to be 21MUM. BEHP was
      able to induce apoptosis involving caspases pathway, besides regulating
      mitochondrial enzymes. Further, western blot analysis revealed the activation of
      caspases family proteins viz., caspase 8, caspase-9 and caspase-3. An increase in
      the expression of Bax mRNA concomitant with a decrease in mRNA of Bcl-2 in BEHP
      treated K562 cells was also observed. AO/EB staining of BEHP treated K562 cells
      further confirmed the progression of apoptosis as evidenced by morphological
      changes including nuclear condensation, cell shrinkage, and formation of
      apoptotic bodies. Treatment of K562 cells with BEHP induced the progressive
      accumulation of fragmented DNA in a time dependent manner. This pattern appeared
      as a typical laddering distribution of DNA fragmentation due to intranucleosomal
      cleavage associated with apoptosis. Based on flow cytometric analysis it has
      become evident that the compound was also effective in arresting the cell cycle
      at a sub G0/G1 phase.

PMID- 22155659
TI  - High rate of Staphylococcus aureus oropharyngeal colonization in children.

PMID- 22155660
TI  - The dynamic allocation of attention to emotion: simultaneous and independent
      evidence from the late positive potential and steady state visual evoked
      potentials.
AB  - Emotional stimuli capture and hold attention without explicit instruction. The
      late positive potential (LPP) component of the event related potential can be
      used to track motivated attention toward emotional stimuli, and is larger for
      emotional compared to neutral pictures. In the frequency domain, the steady state
      visual evoked potential (ssVEP) has also been used to track attention to stimuli
      flickering at a particular frequency. Like the LPP, the ssVEP is also larger for
      emotional compared to neutral pictures. Prior work suggests that both the LPP and
      ssVEP are sensitive to "top-down" manipulations of attention, however the LPP and
      ssVEP have not previously been examined using the same attentional manipulation
      in the same participants. In the present study, LPP and ssVEP amplitudes were
      simultaneously elicited by unpleasant and neutral pictures. Partway through
      picture presentation, participants' attention was directed toward an arousing or
      non-arousing region of unpleasant pictures. In line with prior work, the LPP was
      reduced when attention was directed toward non-arousing compared to arousing
      regions of unpleasant pictures; similar results were observed for the ssVEP.
      Thus, both electrocortical measures index affective salience and are sensitive to
      directed (here: spatial) attention. Variation in the LPP and ssVEP was unrelated,
      suggesting that these measures are not redundant with each other and may capture
      different neurophysiological aspects of affective stimulus processing and
      attention.

PMID- 22155661
TI  - Ugandan AIDS care workers realign strategies as Global Fund cuts grants.

PMID- 22155662
TI  - Commission will tell doctors they can raise concerns about practice even if they
      have signed secrecy agreements.

PMID- 22155663
TI  - Health secretary unveils 60 new performance indicators.

PMID- 22155664
TI  - TB incidence in UK decreases for first time in two decades.

PMID- 22155665
TI  - Productivity in NHS has been seriously neglected, meeting hears.

PMID- 22155666
TI  - Research into neglected diseases falls for first time since 2007.

PMID- 22155668
TI  - Dynamics and 3D organization of secretory organelles of Toxoplasma gondii.
AB  - Micronemes, rhoptries and dense granules are secretory organelles of Toxoplasma
      gondii crucial for host cell invasion and formation of the parasitophorous
      vacuole (PV). We examined whether their relative volumes change during the
      intracellular cycle. Stereological analysis of random ultrathin sections taken at
      5min of interaction, 7 and 24h post-infection demonstrated that the relative
      volume of each type of organelle decreases just after the respective peak of
      secretion. Micronemes are radially arranged below the polar ring, while rhoptries
      converge to but only a few reach the inside of the conoid. In contrast to the
      apical and polarized organelles, dense granules were found scattered throughout
      the cytoplasm, with no preferential location in the parasite cell body. Extensive
      observation of random sections indicated that each organelle probably secretes in
      a different region. Micronemes secrete just below the posterior ring and probably
      require that the conoid is extruded. The rhoptries passing through the conoid
      secrete at a porosome-like point at the most apical region. Dense granules
      secrete laterally, probably at fenestrations in the inner membrane complex.
      Immunocytochemistry showed that there are no subpopulations of rhoptries or dense
      granules, as a single organelle can contain more than one kind of its specific
      proteins. The vacuolar-like profiles observed at the apical portion of parasites
      just after invasion were confirmed to be empty rhoptries, as they were positively
      labeled for rhoptry proteins. These findings contribute for a better
      understanding of the essential behavior of secretory organelles.

PMID- 22155667
TI  - Evolutionary bidirectional expansion for the tracing of alpha helices in cryo
      electron microscopy reconstructions.
AB  - Cryo-electron microscopy (cryo-EM) enables the imaging of macromolecular
      complexes in near-native environments at resolutions that often permit the
      visualization of secondary structure elements. For example, alpha helices
      frequently show consistent patterns in volumetric maps, exhibiting rod-like
      structures of high density. Here, we introduce VolTrac (Volume Tracer) - a novel
      technique for the annotation of alpha-helical density in cryo-EM data sets.
      VolTrac combines a genetic algorithm and a bidirectional expansion with a tabu
      search strategy to trace helical regions. Our method takes advantage of the
      stochastic search by using a genetic algorithm to identify optimal placements for
      a short cylindrical template, avoiding exploration of already characterized tabu
      regions. These placements are then utilized as starting positions for the
      adaptive bidirectional expansion that characterizes the curvature and length of
      the helical region. The method reliably predicted helices with seven or more
      residues in experimental and simulated maps at intermediate (4-10A) resolution.
      The observed success rates, ranging from 70.6% to 100%, depended on the map
      resolution and validation parameters. For successful predictions, the helical
      axes were located within 2A from known helical axes of atomic structures.

PMID- 22155669
TI  - Molecular insights into substrate specificity and thermal stability of a
      bacterial GH5-CBM27 endo-1,4-beta-D-mannanase.
AB  - The breakdown of beta-1,4-mannoside linkages in a variety of mannan-containing
      polysaccharides is of great importance in industrial processes such as kraft pulp
      delignification, food processing and production of second-generation biofuels,
      which puts a premium on studies regarding the prospection and engineering of beta
      mannanases. In this work, a two-domain beta-mannanase from Thermotoga petrophila
      that encompasses a GH5 catalytic domain with a C-terminal CBM27 accessory domain,
      was functionally and structurally characterized. Kinetic and thermal denaturation
      experiments showed that the CBM27 domain provided thermo-protection to the
      catalytic domain, while no contribution on enzymatic activity was observed. The
      structure of the catalytic domain determined by SIRAS revealed a canonical
      (alpha/beta)(8)-barrel scaffold surrounded by loops and short helices that form
      the catalytic interface. Several structurally related ligand molecules
      interacting with TpMan were solved at high-resolution and resulted in a wide
      range representation of the subsites forming the active-site cleft with residues
      W134, E198, R200, E235, H283 and W284 directly involved in glucose binding.

PMID- 22155671
TI  - Changes in histone H4 acetylation during in vivo versus in vitro maturation of
      equine oocytes.
AB  - Epigenetic modifications are established during gametogenesis and preimplantation
      embryonic development. Any disturbance of the normal natural environment during
      these critical phases could cause alterations of the epigenetic signature.
      Histone acetylation is an important epigenetic modification involved in the
      regulation of chromatin organization and gene expression. The present study was
      aimed to determine whether the proper establishment of post-translational histone
      H4 acetylation at lysine 8 (AcH4K8), 12 (AcH4K12) and 16 (AcH4K16) of equine
      oocytes is adversely affected during in vitro maturation (IVM) when compared with
      in vivo matured oocytes collected from naturally cycling mares not undergoing
      ovarian hyperstimulation. The acetylation patterns were investigated by means of
      indirect immunofluorescence staining with specific antibodies directed against
      the acetylated lysine residues. Our results indicate that the acetylation state
      of H4 is dependent on the chromatin configuration in immature germinal vesicle
      (GV) stage oocytes and it changes in a residue-specific manner along with the
      increase of chromatin condensation. In particular, the levels of AcH4K8 and
      AcH4K12 increased significantly, while AcH4K16 decreased significantly from the
      fibrillar to the condensed state of chromatin configuration within the GV.
      Moreover, during meiosis, K8 and K12 were substantially deacetylated without any
      differences between in vivo and in vitro conditions, while K16 displayed a strong
      acetylation in oocytes matured in vivo, and in contrast, it was markedly
      deacetylated following IVM. Although the functional meaning of residue-specific
      acetylation during oocyte differentiation and meiotic resumption needs further
      investigation, our results support the hypothesis that IVM conditions can
      adversely affect oocyte ability to regulate the epigenetic reprogramming,
      critical for successful meiosis and subsequent embryonic development.

PMID- 22155670
TI  - The plastid outer envelope protein OEP16 affects metabolic fluxes during ABA
      controlled seed development and germination.
AB  - Previously, the OEP16.1 channel pore in the outer envelope membrane of mature pea
      (Pisum sativum) chloroplasts in vitro has been characterized to be selective for
      amino acids. Isolation of OEP16.2, a second OEP16 isoform from pea, in the
      current study allowed membrane localization and gene expression of OEP16 to be
      followed throughout seed development and germination of Arabidopsis thaliana and
      P. sativum. Thereby it can be shown on the transcript and protein level that the
      isoforms OEP16.1 and OEP16.2 in both plant species are alternating: whereas
      OEP16.1 is prominent in early embryo development and first leaves of the growing
      plantlet, OEP16.2 dominates in late seed development stages, which are associated
      with dormancy and desiccation, as well as early germination events. Further,
      OEP16.2 expression in seeds is under control of the phytohormone abscisic acid
      (ABA), leading to an ABA-hypersensitive phenotype of germinating oep16 knockout
      mutants. In consequence, the loss of OEP16 causes metabolic imbalance, in
      particular that of amino acids during seed development and early germination. It
      is thus concluded that in vivo OEP16 most probably functions in shuttling amino
      acids across the outer envelope of seed plastids.

PMID- 22155672
TI  - Anti-leishmanial activity of the bisnaphthalimidopropyl derivatives.
AB  - Bisnaphthalimidopropyl (BNIP) derivatives were recently identified as inhibitors
      of the Leishmania Silent Information Regulator 2 (SIR2) NAD(+)-dependent
      deacetylase. In this report we have for the first time, determined the potential
      of these compounds to treat visceral leishmaniasis using BALB/c mice chronically
      infected with Leishmania infantum as a model. These experiments led to the
      identification of BNIPdiaminooctane (BNIPDaoct) as an effective compound able to
      induce significant reduction of the parasite load in the spleen and in the liver.
      Indeed, at a dose of 1mg/kg, BNIPDaoct was more effective to treat leishmaniasis
      in a short course treatment (3 or 6 drug administrations) than the standard
      amphotericin B. Moreover, no indications of hematological toxicity were detected
      as evaluated by the hemoglobin, hematocrit, white and red blood cell counts,
      hence making BNIPDaoct a potential therapeutic agent against leishmaniasis.

PMID- 22155673
TI  - Evaluation of a Web-based intervention to promote hand hygiene: exploratory
      randomized controlled trial.
AB  - BACKGROUND: Hand-washing is regarded as a potentially important behavior for
      preventing transmission of respiratory infection, particularly during a pandemic.
      OBJECTIVE: The objective of our study was to evaluate whether a Web-based
      intervention can encourage more frequent hand-washing in the home, and to examine
      potential mediators and moderators of outcomes, as a necessary first step before
      testing effects of the intervention on infection rates in the PRIMIT trial
      (PRimary care trial of a website based Infection control intervention to Modify
      Influenza-like illness and respiratory infection Transmission). METHODS: In a
      parallel-group pragmatic exploratory trial design, 517 nonblinded adults
      recruited through primary care were automatically randomly assigned to a fully
      automated intervention comprising 4 sessions of tailored motivational messages
      and self-regulation support (n = 324) or to a no-intervention control group (n =
      179; ratio 2:1). Hand-washing frequency and theory of planned behavior cognitions
      relating to hand-washing were assessed by online questionnaires at baseline (in
      only half of the control participants, to permit evaluation of effects of
      baseline assessment on effect sizes), at 4 weeks (postintervention; all
      participants), and at 12 weeks. RESULTS: Hand-washing rates in the intervention
      group were higher at 4 weeks than in the control group (mean 4.40, n = 285 and
      mean 4.04, n = 157, respectively; P < .001, Cohen d = 0.42) and remained higher
      at 12 weeks (mean 4.45, n = 282 and mean 4.12, n = 154, respectively; P < .001,
      Cohen d = 0.34). Hand-washing intentions and positive attitudes toward hand
      washing increased more from baseline to 4 weeks in the intervention group than in
      the control group. Mediation analyses revealed positive indirect effects of the
      intervention on change in hand-washing via intentions (coefficient = .15, 95%
      confidence interval [CI], .08-.26) and attitudes (coefficient = 0.16, 95% CI, .09
      .26). Moderator analyses confirmed that the intervention was similarly effective
      for men and women, those of higher and lower socioeconomic status, and those with
      higher and lower levels of perceived risk. CONCLUSIONS: This study provides
      promising evidence that Web-based interventions could potentially provide an
      effective method of promoting hand hygiene in the home. Data were collected
      during the 2010 influenza pandemic, when participants in both groups had already
      been exposed to extensive publicity about the need for hand hygiene, suggesting
      that our intervention could add to existing public health campaigns. However,
      further research is required to determine the effects of the intervention on
      actual infection rates. TRIAL: International Standard Randomized Controlled Trial
      Number (ISRCTN): 75058295; http://www.controlled-trials.com/ISRCTN75058295
      (Archived by WebCite at http://www.webcitation.org/62KSbkNmm).

PMID- 22155674
TI  - Status of cellular immunity lacks prognostic significance in vulvar squamous
      carcinoma.
AB  - OBJECTIVE: It is generally recognized that the immune system has an important
      role in regulating cancer development. Evidence indicating a prognostic role of
      the immune system in vulvar carcinoma is scarce. This study investigated the
      presence and prognostic significance of several aspects of the immune system in
      vulvar squamous carcinoma. METHODS: The number of intratumoral CD8(+) and
      Foxp3(+) T-lymphocytes, next to HLA class I (HLA-A, HLA-B/C and beta(2)-m) and
      indoleamine 2,3-dioxygenase (IDO) expression was determined by
      immunohistochemistry in a consecutively selected cohort of 286 vulvar squamous
      carcinoma patients, all treated in the University Medical Center Groningen, the
      Netherlands. Associations between immunohistochemistry expression and the
      influence on survival were determined. RESULTS: The number of tumor-infiltrating
      CD8(+) T-lymphocytes was significantly lower in tumors with loss of HLA-A
      (p=0.004), HLA-B/C (p=0.024) or beta(2)-m (p=0.025) expression compared with
      tumors with expression of HLA class I. No association was found between the
      number of intratumoral CD8(+) T-lymphocytes and Foxp3(+) T-lymphocytes, HLA class
      I and IDO expression and survival of vulvar squamous carcinoma patients.
      CONCLUSION: Our results indicate that the immune system does not seem to have a
      major influence on prognosis of patients with vulvar squamous carcinoma.

PMID- 22155675
TI  - Carcinosarcoma of the ovary: a review of the literature.
AB  - OBJECTIVE: Carcinosarcoma of the ovary is a rare tumor with a grim prognosis.
      This article critically reviews the literature pertinent to the pathology,
      pathogenesis, diagnosis, management, and outcome of patients with ovarian
      carcinosarcoma (OCS). METHODS: MEDLINE was searched for all research articles
      published in English between January 1, 1981 and August 30, 2011 which reported
      on patients diagnosed with carcinosarcoma of the ovary. Given the rarity of this
      tumor, studies were not limited by design or number of reported patients.
      RESULTS: Patients with OCS generally present with advanced stage disease, and
      symptoms similar to those of patients with epithelial ovarian cancer (EOC).
      Retrospective studies have shown that cytoreductive surgery improves outcomes in
      patients with OCS. Similarly, platinum-based chemotherapy appears to be active in
      the treatment of OCS. CONCLUSIONS: Ovarian carcinosarcomas are rare and
      aggressive tumors, associated with a poor prognosis. The mainstay of treatment
      remains cytoreductive surgical effort for metastatic disease followed by platinum
      based chemotherapy. The role of targeted therapies may be promising in the
      treatment of OCS.

PMID- 22155676
TI  - A systematic review evaluating the relationship between progression free survival
      and post progression survival in advanced ovarian cancer.
AB  - OBJECTIVE: Although overall survival is the ultimate goal of cancer therapy, many
      clinical and health economic decisions are taken when only progression free
      survival (PFS) data are available. This study evaluates the relationship between
      PFS and post progression survival (i.e. the time between disease progression and
      death) to estimate how many months a new drug for ovarian cancer might add to
      overall survival if the number of months the drug added to PFS (relative to a
      standard drug) was already known. METHODS: A literature search was conducted over
      Medline for randomised controlled trials published between January 1990 and July
      2010 that evaluated the effect of a drug treatment in comparison to alternative
      drug treatment in patients with either advanced stage primary or recurrent
      ovarian cancer. A systematic review of progression free and post progression
      survival (PPS) was performed. The relationship between PFS and PPS was evaluated
      by a graphical method and standard statistical tests. RESULTS: Thirty-seven
      trials involving 15,850 patients met the inclusion criteria. The review found
      that increases in median PFS generally lead to little change in post-progression
      survival. Percentage gains in PFS are generally associated with no percentage
      gains or with very slight percentage gains or losses in post-progression survival
      CONCLUSION: If the effect of a new drug treatment for ovarian cancer is to extend
      median PFS by x months, then it is reasonable to estimate that the treatment will
      also extend median overall survival by x months. This information will be useful
      for individual and collective decision making.

PMID- 22155677
TI  - Pattern analysis of regional spread and therapeutic lymph node dissection in
      cervical cancer based on ontogenetic anatomy.
AB  - OBJECTIVE: In cervical cancer lymph node dissection is applied for regional tumor
      staging. Up to now, the use of (chemo)radiation in the nodal positive patient has
      prevented the exact pattern analysis of regional tumor spread and the evaluation
      of the therapeutic role of lymph node dissection. New surgical techniques founded
      on ontogenetic instead of functional anatomy for the treatment of cervical cancer
      dispensing with adjuvant radiotherapy offer the possibility to accurately
      determine the topography of regional lymph node metastases which is the
      prerequisite for optimized diagnostic and therapeutic lymph node dissection.
      METHODS: Patients with cervical cancer FIGO stages IB-IIB were treated with total
      mesometrial resection (TMMR) and lymph node dissection after exposing the
      ontogenetic visceroparietal compartments of the female pelvis. Resected lymph
      nodes were allocated to regions topographically defined by the embryonic
      development of the iliac, lumbar and mesenteric lymph systems prior to
      histopathological assessment. RESULTS: 71 of 305 treated patients had lymph node
      metastases. Topographic distribution of these metastases at primary surgery and
      analysis of pelvic failures showed a spatial pattern related to the ontogenesis
      of the abdominopelvic lymphatic system. Five-year locoregional tumor control
      probability was 96% (95% CI: 94-98) for the whole group and 87% (95% CI: 77-97)
      for nodal positive patients. CONCLUSIONS: The pattern of regional spread in
      cervical cancer can be comprehended and predicted from ontogenetic lymphatic
      compartments. In patients with early cervical cancer lymph node dissection based
      on ontogenetic anatomy achieves high regional tumor control without adjuvant
      radiation.

PMID- 22155678
TI  - Association of number of positive nodes and cervical stroma invasion with outcome
      of advanced endometrial cancer treated with chemotherapy or whole abdominal
      irradiation: a Gynecologic Oncology Group study.
AB  - OBJECTIVE: To determine whether the number of positive pelvic nodes (PPN),
      cervical stromal involvement (CSI), and/or lymphovascular space involvement
      (LVSI) were prognostic factors among women with advanced endometrial carcinoma
      treated with adriamycin plus cisplatin (AP) or whole abdominal irradiation (WAI).
      METHODS: Data were abstracted from records of patients treated with adjuvant WAI
      or AP in a GOG randomized trial. Cox proportional hazards models were used to
      estimate the association of CSI and PPN with differences in PFS and OS while
      adjusting for treatment and previously studied factors. RESULTS: WAI was randomly
      allocated to 202 and AP to 194 eligible patients. CSI (n=93 total) was associated
      with a 44% increase in risk of progression and a 33% increase in risk of death.
      There was a trend for increasing number PPN being associated with a 7% per
      positive node increase in risk of progression/death. For CSI, the estimated
      unadjusted treatment hazard ratios (HRs) were: PFS 0.85 (0.53, 1.38); OS 0.81
      (0.50, 1.33). For metastatic disease limited to a single PPN (n=25), the
      unadjusted HRs were: PFS 0.96 (0.34, 2.74); OS 0.73 (0.24, 2.18). The test of
      homogeneity of treatment effect (ie., AP vs WAI) across subgroups (CSI, number of
      positive pelvic nodes) was not statistically significant for either endpoint,
      thus supporting the superiority of chemotherapy as reported in the original
      manuscript. CONCLUSIONS: The presence of CSI and increasing number of PPN were
      associated with poor prognosis. On average, patients with CSI experienced
      improved PFS and OS when treated with AP relative to WAI.

PMID- 22155679
TI  - Causal structure learning over time: observations and interventions.
AB  - Seven studies examined how people learn causal relationships in scenarios when
      the variables are temporally dependent - the states of variables are stable over
      time. When people intervene on X, and Y subsequently changes state compared to
      before the intervention, people infer that X influences Y. This strategy allows
      people to learn causal structures quickly and reliably when variables are
      temporally stable (Experiments 1 and 2). People use this strategy even when the
      cover story suggests that the trials are independent (Experiment 3). When
      observing variables over time, people believe that when a cause changes state,
      its effects likely change state, but an effect may change state due to an
      exogenous influence in which case its observed cause may not change state at the
      same time. People used this strategy to learn the direction of causal relations
      and a wide variety of causal structures (Experiments 4-6). Finally, considering
      exogenous influences responsible for the observed changes facilitates learning
      causal directionality (Experiment 7). Temporal reasoning may be the norm rather
      than the exception for causal learning and may reflect the way most events are
      experienced naturalistically.

PMID- 22155680
TI  - Time- and state-dependent effects of methanethiosulfonate ethylammonium (MTSEA)
      exposure differ between heart and skeletal muscle voltage-gated Na(+) channels.
AB  - The substituted-cysteine scanning method (SCAM) is used to study conformational
      changes in proteins. Experiments using SCAM involve site-directed mutagenesis to
      replace native amino acids with cysteine and subsequent exposure to a
      methanethiosulfonate (MTS) reagent such as methanethiosulfonate ethylammonium
      (MTSEA). These reagents react with substituted-cysteines and can provide
      functional information about relative positions of amino acids within a protein.
      In the human heart voltage-gated Na(+) channel hNav1.5 there is a native cysteine
      at position C373 that reacts rapidly with MTS reagents resulting in a large
      reduction in whole-cell Na(+) current (I(Na)). Therefore, in order to use SCAM in
      studies in this isoform, this native cysteine is mutated to a non-reactive
      residue, e.g., tyrosine. This mutant, hNav1.5-C373Y, is resistant to the MTS
      mediated decrease in I(Na). Here we show that this resistance is time- and state
      dependent. With relatively short exposure times to MTSEA (<4min), there is little
      effect on I(Na). However, with longer exposures (4-8min), there is a large
      decrease in I(Na), but this effect is only found when hNav1.5-C373Y is
      inactivated (fast or slow) - MTSEA has little effect in the closed state.
      Additionally, this long-term, state-dependent effect is not seen in human
      skeletal muscle Na(+) channel isoform hNav1.4, which has a native tyrosine at the
      homologous site C407. We conclude that differences in molecular determinants of
      inactivation between hNav1.4 and hNav1.5 underlie the difference in response to
      MTSEA exposure.

PMID- 22155681
TI  - Plant VDAC: facts and speculations.
AB  - The voltage-dependent anion-selective channel (VDAC) is the most abundant protein
      in the mitochondrial outer membrane and the major transport pathway for a large
      variety of compounds ranging from ions to large polymeric molecules such as DNA
      and tRNA. Plant VDACs feature a secondary structure content and
      electrophysiological properties akin to those of VDACs from other organisms. They
      however undergo a specific regulation. The general importance of VDAC in plant
      physiology has only recently emerged. Besides their role in metabolite transport,
      plant VDACs are also involved in the programmed cell death triggered in response
      to biotic and abiotic stresses. Moreover, their colocalization in non
      mitochondrial membranes suggests a diversity of function. This review summarizes
      our current understanding of the structure and function of plant VDACs. This
      article is part of a Special Issue entitled: VDAC structure, function, and
      regulation of mitochondrial metabolism.

PMID- 22155682
TI  - Structural and biophysical characterization of an antimicrobial peptide chimera
      comprised of lactoferricin and lactoferrampin.
AB  - Lactoferricin and lactoferrampin are two antimicrobial peptides found in the N
      terminal lobe of bovine lactoferrin with broad spectrum antimicrobial activity
      against a range of Gram-positive and Gram-negative bacteria as well as Candida
      albicans. A heterodimer comprised of lactoferrampin joined to a fragment of
      lactoferricin was recently reported in which these two peptides were joined at
      their C-termini through the two amino groups of a single Lys residue (Bolscher et
      al., 2009, Biochimie 91(1):123-132). This hybrid peptide, termed LFchimera, has
      significantly higher antimicrobial activity compared to the individual peptides
      or an equimolar mixture of the two. In this work, the underlying mechanism behind
      the increased antibacterial activity of LFchimera was investigated. Differential
      scanning calorimetry studies demonstrated that all the peptides influenced the
      thermotropic phase behaviour of anionic phospholipid suspensions. Calcein leakage
      and vesicle fusion experiments with anionic liposomes revealed that LFchimera had
      enhanced membrane perturbing properties compared to the individual peptides.
      Peptide structures were evaluated using circular dichroism and NMR spectroscopy
      to gain insight into the structural features of LFchimera that contribute to the
      increased antimicrobial activity. The NMR solution structure, determined in a
      miscible co-solvent mixture of chloroform, methanol and water, revealed that the
      Lys linkage increased the helical content in LFchimera compared to the individual
      peptides, but it did not fix the relative orientations of lactoferricin and
      lactoferrampin with respect to each other. The structure of LFchimera provides
      insight into the conformation of this peptide in a membranous environment and
      improves our understanding of its antimicrobial mechanism of action.

PMID- 22155683
TI  - Structure, dynamics, and hydration of POPC/POPS bilayers suspended in NaCl, KCl,
      and CsCl solutions.
AB  - Effects of alkali metal chlorides on the properties of mixed negatively charged
      lipid bilayers are experimentally measured and numerically simulated. Addition of
      20mol% of negatively charged phosphatidylserine to zwitterionic
      phosphatidylcholine strengthens adsorption of monovalent cations revealing their
      specificity, in the following order: Cs(+)<K(+)<Na(+). Time-resolved fluorescence
      solvent relaxation shows significant decrease both in mobility and hydration of
      the lipid carbonyls probed by Laurdan upon addition of the cations. The
      experimental findings are supported by molecular dynamics simulations, which show
      deep penetration of the cations down to the glycerol level of the lipid bilayer
      where they pair with oxygen atoms of carbonyl groups (with pairing with sn-2
      carbonyl being about twice stronger than pairing with the sn-1 one). Moreover,
      the cations bridge neighboring lipids forming clusters of up to 4 lipid
      molecules, which decreases the area per lipid, thickens the membrane, causes
      rising of lipid headgroups, and hinders lipid dynamics. All these effects follow
      the same Hofmeister ordering as the cationic adsorption to the bilayer.

PMID- 22155684
TI  - Effects of an antimalarial quinazoline derivative on human erythrocytes and on
      cell membrane molecular models.
AB  - Plasmodium, the parasite which causes malaria in humans multiplies in the liver
      and then infects circulating erythrocytes. Thus, the role of the erythrocyte cell
      membrane in antimalarial drug activity and resistance has key importance. The
      effects of the antiplasmodial N(6)-(4-methoxybenzyl)quinazoline-2,4,6-triamine
      (M4), and its inclusion complex (M4/HPbetaCD) with 2-hydroxypropyl-beta
      cyclodextrin (HPbetaCD) on human erythrocytes and on cell membrane molecular
      models are herein reported. This work evidences that M4/HPbetaCD interacts with
      red cells as follows: a) in scanning electron microscopy (SEM) studies on human
      erythrocytes induced shape changes at a 10MUM concentration; b) in isolated
      unsealed human erythrocyte membranes (IUM) a concentration as low as 1MUM induced
      sharp DPH fluorescence anisotropy decrease whereas increasing concentrations
      produced a monotonically decrease of DPH fluorescence lifetime at 37 degrees C;
      c) X-ray diffraction studies showed that 200MUM induced a complete structural
      perturbation of dimyristoylphosphatidylcholine (DMPC) bilayers whereas no
      significant effects were detected in dimyristoylphosphatidylethanolamine (DMPE)
      bilayers, classes of lipids present in the outer and inner monolayers of the
      human erythrocyte membrane, respectively; d) fluorescence spectroscopy data
      showed that increasing concentrations of the complex interacted with the deep
      hydrophobic core of DMPC large unilamellar vesicles (LUV) at 18 degrees C. All
      these experiments are consistent with the insertion of M4/HPbetaCD in the outer
      monolayer of the human erythrocyte membrane; thus, it can be considered a
      promising and novel antimalarial agent.

PMID- 22155685
TI  - NMR structure and dynamics of a designed water-soluble transmembrane domain of
      nicotinic acetylcholine receptor.
AB  - The nicotinic acetylcholine receptor (nAChR) is an important therapeutic target
      for a wide range of pathophysiological conditions, for which rational drug
      designs often require receptor structures at atomic resolution. Recent proof-of
      concept studies demonstrated a water-solubilization approach to structure
      determination of membrane proteins by NMR (Slovic et al., PNAS, 101: 1828-1833,
      2004; Ma et al., PNAS, 105: 16537-42, 2008). We report here the computational
      design and experimental characterization of WSA, a water-soluble protein with
      ~83% sequence identity to the transmembrane (TM) domain of the nAChR alpha1
      subunit. Although the design was based on a low-resolution structural template,
      the resulting high-resolution NMR structure agrees remarkably well with the
      recent crystal structure of the TM domains of the bacterial Gloeobacter violaceus
      pentameric ligand-gated ion channel (GLIC), demonstrating the robustness and
      general applicability of the approach. NMR T(2) dispersion measurements showed
      that the TM2 domain of the designed protein was dynamic, undergoing
      conformational exchange on the NMR timescale. Photoaffinity labeling with
      isoflurane and propofol photolabels identified a common binding site in the
      immediate proximity of the anesthetic binding site found in the crystal structure
      of the anesthetic-GLIC complex. Our results illustrate the usefulness of high
      resolution NMR analyses of water-solubilized channel proteins for the discovery
      of potential drug binding sites.

PMID- 22155686
TI  - Allopregnanolone prevents memory impairment: effect on mRNA expression and
      enzymatic activity of hippocampal 3-alpha hydroxysteroid oxide-reductase.
AB  - In this work we investigated how the neurosteroid allopregnanolone can modulate
      learning and memory processes. For this purpose, we used ovariectomized (OVX)
      rats subcutaneously injected with oestradiol benzoate (E) alone or E and
      progesterone (P). Then, rats were injected in dorsal hippocampus with
      allopregnanolone or vehicle. Animals were tested in inhibitory avoidance task (IA
      task). After behavioural test hippocampal mRNA expression and enzymatic activity
      of 3alpha-HOR, the enzyme responsible of allopregnanolone synthesis, were
      analysed. In IA task OVX-EP rats spent less time on platform, compared to those
      OVX or OVX-E. Regression analyses revealed that there was a significant negative
      relationship between E-P infusion and performance in this task. Pre-training
      allopregnanolone administration to OVX-EP rats increased the time spent on the
      platform. Interestingly, when enzymatic activity of 3alpha-HOR was tested, OVX-EP
      rats showed a significant decrease in the enzymatic activity, compared with OVX
      and OVX-E rats. In addition, OVX-EP group showed a significant increase in the
      enzymatic activity after intrahippocampal infusion of allopregnanolone. On the
      other hand, when mRNA expression of 3alpha-HOR was analysed no differences were
      observed when the hippocampal allopregnanolone injection was done. These results
      suggest that E and P have amnesic effects on female rats, being reversed by
      allopregnanolone through its modulation on hippocampal 3alpha-HOR activity.

PMID- 22155687
TI  - An endogenous dopaminergic tone acting on dopamine D3 receptors may be involved
      in diurnal changes of tuberoinfundibular dopaminergic neuron activity and
      prolactin secretion in estrogen-primed ovariectomized rats.
AB  - The diurnal rhythm of tuberoinfundibular dopaminergic (TIDA) neuron activity,
      i.e., high in the morning and low in the afternoon, is prerequisite for the
      afternoon prolactin (PRL) surge in proestrous and estrogen-primed ovariectomized
      (OVX) female rats. Whether dopamine acts via D(3) receptors in regulating the
      rhythmic TIDA neuron activity and PRL secretion in estrogen-primed OVX (OVX+E(2))
      rats is the focus of this study. Intracerebroventricular (icv) injection of a
      D(3) receptor agonist, PD128907 (0.1-10 MUg/3 MUl), in the morning significantly
      reduced the basal activity of TIDA neurons and increased plasma PRL level. The
      effects of PD128907 were reversed by co-administration of U99194A, a D(3)
      receptor antagonist, but not by raclopride, a D(2) receptor antagonist. To
      determine whether endogenous dopamine acts on D(3) receptors involved in the
      diurnal changes of the activities, we used both U99194A, a D(3) receptor
      antagonist, and an antisense oligodeoxynucleotide (ODN) against D(3) receptor
      mRNA in the study. U99194A (0.1 MUg/3 MUl, icv) given at 1200 h significantly
      reversed the lowered TIDA neuron activity and the afternoon PRL surge at 1500 h.
      Moreover, OVX+E(2) rats pretreated with the antisense ODN (10 MUg/3 MUl, icv) for
      2 days had the same effects as the D(3) receptor antagonist on TIDA neuron
      activity and the PRL surge. The same treatment with sense ODN had no effect. In
      conclusion, an endogenous DA tone may act on D(3) receptors to inhibit TIDA
      neuron activity and in turn stimulate the PRL surge in the afternoon of OVX+E(2)
      rats.

PMID- 22155688
TI  - A genome sequence resource for the aye-aye (Daubentonia madagascariensis), a
      nocturnal lemur from Madagascar.
AB  - We present a high-coverage draft genome assembly of the aye-aye (Daubentonia
      madagascariensis), a highly unusual nocturnal primate from Madagascar. Our
      assembly totals ~3.0 billion bp (3.0 Gb), roughly the size of the human genome,
      comprised of ~2.6 million scaffolds (N50 scaffold size = 13,597 bp) based on
      short paired-end sequencing reads. We compared the aye-aye genome sequence data
      with four other published primate genomes (human, chimpanzee, orangutan, and
      rhesus macaque) as well as with the mouse and dog genomes as nonprimate
      outgroups. Unexpectedly, we observed strong evidence for a relatively slow
      substitution rate in the aye-aye lineage compared with these and other primates.
      In fact, the aye-aye branch length is estimated to be ~10% shorter than that of
      the human lineage, which is known for its low substitution rate. This finding may
      be explained, in part, by the protracted aye-aye life-history pattern, including
      late weaning and age of first reproduction relative to other lemurs.
      Additionally, the availability of this draft lemur genome sequence allowed us to
      polarize nucleotide and protein sequence changes to the ancestral primate lineage
      a critical period in primate evolution, for which the relevant fossil record is
      sparse. Finally, we identified 293,800 high-confidence single nucleotide
      polymorphisms in the donor individual for our aye-aye genome sequence, a captive
      born individual from two wild-born parents. The resulting heterozygosity estimate
      of 0.051% is the lowest of any primate studied to date, which is understandable
      considering the aye-aye's extensive home-range size and relatively low population
      densities. Yet this level of genetic diversity also suggests that conservation
      efforts benefiting this unusual species should be prioritized, especially in the
      face of the accelerating degradation and fragmentation of Madagascar's forests.

PMID- 22155690
TI  - Age-related deterioration in trabecular bone mechanical properties at material
      level: nanoindentation study of the femoral neck in women by using AFM.
AB  - Despite general belief that the mechanical properties of bone material contribute
      to whole bone strength, it is still obscure what the age effects are on
      mechanical behavior of the bone material, particularly in the case of the femoral
      neck trabeculae. In this study, atomic force microscopy was used for imaging and
      measuring the size of mineral grains, as well as nano-scale mechanical
      characterization (nanoindentation) of the bone mineralized matrix of trabeculae,
      with the aim to explore the age effects on bone elasticity and give new insight
      into age-related bone fragility. The bone samples in this study comprised
      trabecular bone specimens of the femoral neck region, collected from eight
      skeletal healthy women (five young adults: 27-38yrs., three elderly: 83-94yrs.)
      at autopsy. Bone trabeculae in the elderly displayed a higher modulus and
      nanohardness, signifying a decreased amount of energy that can be accommodated by
      the bone tissue during loading. Regression analysis revealed that nearly 65% of
      variability in the bone matrix elastic modulus can be statistically explained by
      the changes in size of the matrix mineral grains. This study revealed that the
      bone trabeculae of elderly women express less elastic behavior at the material
      level, which makes them more vulnerable to unusual impact loads originating from
      a fall. The observed age-related structural and mechanical alteration at the bone
      material level adds new evidence for understanding why hip fractures are more
      frequent in elderly women.

PMID- 22155689
TI  - Mitochondrial genome sequences of Nematocera (lower Diptera): evidence of
      rearrangement following a complete genome duplication in a winter crane fly.
AB  - The complete mitochondrial DNA sequences of eight representatives of lower
      Diptera, suborder Nematocera, along with nearly complete sequences from two other
      species, are presented. These taxa represent eight families not previously
      represented by complete mitochondrial DNA sequences. Most of the sequences retain
      the ancestral dipteran mitochondrial gene arrangement, while one sequence, that
      of the midge Arachnocampa flava (family Keroplatidae), has an inversion of the
      trnE gene. The most unusual result is the extensive rearrangement of the
      mitochondrial genome of a winter crane fly, Paracladura trichoptera (family
      Trichocera). The pattern of rearrangement indicates that the mechanism of
      rearrangement involved a tandem duplication of the entire mitochondrial genome,
      followed by random and nonrandom loss of one copy of each gene. Another winter
      crane fly retains the ancestral diperan gene arrangement. A preliminary
      mitochondrial phylogeny of the Diptera is also presented.

PMID- 22155691
TI  - Efficacy of ASP2151, a helicase-primase inhibitor, against thymidine kinase
      deficient herpes simplex virus type 2 infection in vitro and in vivo.
AB  - ASP2151 was developed as a novel inhibitor of herpes simplex virus (HSV) and
      varicella-zoster virus helicase-primase. The anti-HSV activity of ASP2151 toward
      a clinical HSV isolate with acyclovir (ACV)-resistant/thymidine kinase (TK)
      deficiency was characterized in vitro and in vivo using a plaque reduction assay
      and the ear pinna infection in mice. The IC(50) ranged from 0.018 to 0.024
      MUg/ml, indicating the susceptibility of TK-deficient HSV-2 was similar to that
      of wild-type HSV-2 strains. Anti-HSV activity of ASP2151 in vivo was evaluated in
      mice infected with wild-type HSV-2 and TK-deficient HSV-2. ASP2151 significantly
      reduced the copy numbers of wild-type HSV-2 and TK-deficient HSV-2 at the
      inoculation ear pinna, while valacyclovir significantly reduced the copy number
      of wild type HSV-2 but not that of TK-deficient HSV-2 in the inoculated ear
      pinna. Thus, ASP 2151 showed therapeutic efficacy in mice infected with both wild
      type and TK-deficient HSV-2. In conclusion, ASP2151 is a promising novel herpes
      helicase-primase inhibitor that indicates the feasibility of ASP2151 for clinical
      application for the treatment of HSV infections, including ACV-resistant/TK
      deficient HSV infection.

PMID- 22155692
TI  - Extrusion of electroformed giant unilamellar vesicles through track-etched
      membranes.
AB  - Unilamellar vesicle populations having a narrow size distribution and mean radius
      below 100 nm are preferred for drug delivery applications. In the present work,
      1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was used to prepare giant
      unilamellar vesicles (GUVs) by electroformation and multilamellar vesicles (MLVs)
      by thin film hydration. Our experiments show that in contrast to MLVs, a single
      pass extrusion of GUVs through track-etched polycarbonate membranes at moderate
      pressure differences is sufficient to produce small liposomes having low
      polydispersity index. Moreover, we observe that the drug encapsulating potential
      of extruded liposomes obtained from GUVs is significantly higher compared to
      liposomes prepared by extrusion of MLVs. Furthermore, our experiments carried out
      for varying membrane pore diameters and extrusion pressures suggest that the size
      of extruded liposomes is a function of the velocity of GUV suspensions in the
      membrane pore.

PMID- 22155693
TI  - Gene expression profiling in the skin of zebrafish infected with Citrobacter
      freundii.
AB  - Skin is considered the largest immunologically active organ, but its molecular
      mechanism remains unclear in fish. Here, Affymetrix Zebrafish GeneChip was used
      to assess gene expression in the skin of zebrafish (Danio rerio) infected with
      the bacterium Citrobacter freundii. The results showed that 229 genes were
      differentially expressed, of which 196 genes were upregulated and 33 genes were
      downregulated. Gene Ontology and KEGG pathway analyses indicated 88 genes
      significantly associated with skin immunity involved in complement activation and
      acute phase response, defense and immune response, response to stress and
      stimulus, antigen processing and presentation, cell adhesion and migration,
      platelet activation and coagulation factors, regulation of autophagy and
      apoptosis. When compared with transcriptional profiles of previously reported
      carp (Cyprinus carpio) skin, a similar innate immunity (e.g., interferon, lectin,
      heat shock proteins, complements), and several different acute phase proteins
      (transferrin, ceruloplasmin, vitellogenin and alpha-1-microglobulin, etc.) were
      detected in zebrafish skin. The validity of the microarray results was verified
      by quantitative real-time PCR analysis of nine representative genes. This is
      first report that skin play important roles in innate immune responses to
      bacterial infection, which contribute to understanding the defense mechanisms of
      the skin in fish.

PMID- 22155694
TI  - WikiBuild: a new online collaboration process for multistakeholder tool
      development and consensus building.
AB  - BACKGROUND: Production of media such as patient education tools requires methods
      that can integrate multiple stakeholder perspectives. Existing consensus
      techniques are poorly suited to design of visual media, can be expensive and
      logistically demanding, and are subject to caveats arising from group dynamics
      such as participant hierarchies. OBJECTIVE: Our objective was to develop a method
      that enables multistakeholder tool building while averting these difficulties.
      METHODS: We developed a wiki-inspired method and tested this through the
      collaborative design of an asthma action plan (AAP). In the development stage, we
      developed the Web-based tool by (1) establishing AAP content and format options,
      (2) building a Web-based application capable of representing each content and
      format permutation, (3) testing this tool among stakeholders, and (4) revising
      this tool based on stakeholder feedback. In the wiki stage, groups of
      participants used the revised tool in three separate 1-week "wiki" periods during
      which each group collaboratively authored an AAP by making multiple online
      selections. RESULTS: In the development stage, we recruited 16 participants (9/16
      male) (4 pulmonologists, 4 primary care physicians, 3 certified asthma educators,
      and 5 patients) for system testing. The mean System Usability Scale (SUS) score
      for the tool used in testing was 72.2 (SD 10.2). In the wiki stage, we recruited
      41 participants (15/41 male) (9 pulmonologists, 6 primary care physicians, 5
      certified asthma educators, and 21 patients) from diverse locations. The mean SUS
      score for the revised tool was 75.9 (SD 19.6). Users made 872, 466, and 599
      successful changes to the AAP in weeks 1, 2, and 3, respectively. The site was
      used actively for a mean of 32.0 hours per week, of which 3.1 hours per week
      (9.7%) constituted synchronous multiuser use (2-4 users at the same time).
      Participants averaged 23 (SD 33) minutes of login time and made 7.7 (SD 15)
      changes to the AAP per day. Among participants, 28/35 (80%) were satisfied with
      the final AAP, and only 3/34 (9%) perceived interstakeholder group hierarchies.
      CONCLUSION: Use of a wiki-inspired method allowed for effective collaborative
      design of content and format aspects of an AAP while minimizing logistical
      requirements, maximizing geographical representation, and mitigating hierarchical
      group dynamics. Our method faced unique software and hardware challenges, and
      raises certain questions regarding its effect on group functioning. Potential
      uses of our method are broad, and further studies are required.

PMID- 22155695
TI  - Treatment of life-threatening emergencies in the workplace: need for
      collaboration between emergency and occupational health services?

PMID- 22155696
TI  - The potential role of allocation preference, perceived control group inferiority
      and delays to percutaneous coronary reperfusion on patient, consent provider and
      recruiting clinician views of a prehospital induced hypothermia trial.

PMID- 22155698
TI  - Cardiovascular and microvascular responses to mild hypothermia in an ovine model.
AB  - AIMS: Hypothermia is used for brain protection after resuscitation from cardiac
      arrest and other forms of brain injury, but its impact on systemic and tissue
      perfusion has not been well defined. The aim of this study was to evaluate the
      cardiovascular and microvascular responses to mild therapeutic hypothermia (MTH)
      in an ovine model. METHODS: Seven anaesthetised, mechanically ventilated,
      invasively monitored sheep were cooled from a baseline temperature of 39-40
      degrees C to 34 degrees C using cold intravenous fluids, ice packs and transnasal
      cooling. After 6h of MTH, sheep were progressively re-warmed to baseline
      temperature. Positive fluid balance was maintained during the entire study period
      to avoid hypovolemia. In addition to standard haemodynamic assessment, the
      sublingual microcirculation was evaluated using sidestream dark-field (SDF)
      videomicroscopy. RESULTS: MTH was associated with significant decreases in
      cardiac index and left (LVSWI) and right (RVSWI) ventricular stroke work indexes.
      There was a downward shift in the relationship between LVSWI and pulmonary artery
      occlusion pressure during MTH, indicating myocardial depression. During MTH,
      mixed venous oxygen saturation increased, in association with reduced oxygen
      consumption, but blood lactate concentrations increased significantly. There was
      a significant decrease in the proportion and density of small perfused vessels.
      All variables returned to baseline levels during the re-warming phase.
      CONCLUSION: In this large animal model, MTH was associated with decreased
      ventricular function, oxygen extraction and microvascular flow compared to
      normothermia. These changes were associated with increased blood lactate levels.
      These observations suggest that MTH may impair tissue oxygen delivery through
      maldistribution of capillary flow.

PMID- 22155699
TI  - Acute kidney injury after cardiac arrest.
AB  - AIM: Cardiac arrest (CA) in humans causes warm renal ischemia-reperfusion injury,
      similar to animal models of ischemic acute kidney injury (AKI). We aimed to
      investigate the incidence and risk associations of AKI after CA, with or without
      post-resuscitation cardiogenic shock (PRCS). METHODS: We examined the renal
      outcomes of adult patients admitted to the intensive care unit (ICU), who
      survived for more than 48 h following successful resuscitation after CA. RESULTS:
      Of 105 patients (median age 65 years; 69% male), 58 (55.2%) had PRCS and were on
      vasoactive drugs beyond 24h; and 9 (8.6%) (all of whom had PRCS) received renal
      replacement therapy. Only 3 (6.4%) of 47 patients without PRCS had RIFLE-'I'/'F'
      AKI, compared to 30 (51.7%) of 58 patients with PRCS (p<0.001). Median peak serum
      creatinine in the non-PRCS group was 102 MUmol/L (interquartile range 85-115),
      compared to 155 MUmol/L (interquartile range 112-267) (p<0.001) in the PRCS
      group. On multivariate analysis, cumulative noradrenaline dose during the first
      24h in ICU, PRCS, and pre-CA renin-angiotensin-aldosterone-system blockade were
      independently associated with RIFLE-'I'/'F' AKI; while higher serum lactate 12h
      after CA, baseline creatinine, and PRCS were independently associated with
      greater rise in creatinine from pre-CA levels. Estimated time without spontaneous
      circulation, total adrenaline dose and initial cardiac rhythm during CA, had no
      independent associations with renal outcomes. CONCLUSIONS: In the absence of
      PRCS, CA in isolation is uncommonly associated with significant AKI. The human
      kidney may be more resistant to warm ischemia-reperfusion injury than previously
      thought.

PMID- 22155700
TI  - Early- versus late-initiation of therapeutic hypothermia after cardiac arrest:
      preliminary observations from the experience of 17 Italian intensive care units.
AB  - OBJECTIVES: Mild therapeutic hypothermia (TH) has been shown to improve
      neurologic outcome in patients experiencing cardiac arrest after return of
      spontaneous circulation (ROSC). The best timing to initiate TH is currently not
      known. The aim of this study by the ICE (Italian Cooling Experience) group was to
      investigate the relationship between the timing of initiation of therapeutic
      hypothermia (TH) and both patient survival and neurologic outcome. METHODS: In
      this observational prospective clinical study we collected data on cardiac arrest
      patients admitted, after ROSC, to any of the 17 participating Italian intensive
      care units. Patients were managed according to routine clinical practice,
      including, in a group of patients, therapeutic hypothermia. Patients who
      underwent TH were classified, arbitrarily, into an early-initiation group (TH
      started <2 h since cardiac arrest) and a late-initiation group (TH started >2 h
      since cardiac arrest). RESULTS: Intensive care unit (ICU) mortality was 47.4% for
      the early-initiation group and 23.8% for the late-initiation group (P=0.01). Six
      month mortality was 60.8% for the early-initiation group and 40.5% for the late
      initiation group (P=0.04). Cerebral performance category (CPC, a measure of neuro
      cognitive outcome) at ICU discharge was 1 [1-2] for the early-initiation group
      and 1 [1-3] for the late-initiation group (P=0.57). At 6 months, CPC was 1 [1-1]
      for the early-initiation group and 1 [1-2] for the late-initiation group.
      DISCUSSION: Despite similar neurologic outcomes at every time point, mortality
      was significantly higher when therapeutic hypothermia was started within 2h of
      cardiac arrest than when it was started later. Due to the lack of possibility to
      control several putative confounding factors, such results should be considered
      as preliminary observations warranting further research.

PMID- 22155701
TI  - Emergency airway management in Japan: Interim analysis of a multi-center
      prospective observational study.
AB  - OBJECTIVES: Emergency medicine is increasingly recognized as a medical specialty
      in Japan. However, comprehensive studies evaluating emergency airway management
      practice are lacking. We describe emergency department (ED) airway management
      using a large multi-center registry. METHODS: We formed the Japanese Emergency
      Airway Network, a consortium of 10 academic and community medical centers in
      Japan, and prospectively collected data on ED intubations from April 2010 to
      February 2011. All patients undergoing emergency intubation were eligible for
      inclusion. Data were entered in real time by the intubator using a standardized
      data form. Variables included patient's age, sex, weight, indication for
      intubation, methods of intubation, drugs, level of training and specialty of the
      intubator, number of attempts, success or failure, and adverse events. We present
      descriptive data as proportions with 95% confidence intervals. RESULTS: We
      recorded 1486 intubations (compliance rate 99%). Intubation was ultimately
      successful in 99.7%. The initial method of intubation varied substantially among
      the hospitals, including rapid sequence intubation (0-79%), sedation without
      paralysis (4-88%), paralysis without sedation (0-18%), and oral without
      medication (12-67%), in non-cardiac arrest encounters. Success rates in first and
      <=3 attempts ranged from 40 to 83% and from 74 to 100%, respectively. The overall
      adverse event rate was 11%, without significant difference by the method used.
      CONCLUSIONS: In this multi-center study characterizing ED airway management
      across Japan, we observed a high overall success rate but a high degree of
      variation among hospitals in the methods of intubation and success rates.

PMID- 22155702
TI  - A risk score for predicting mortality in patients with asymptomatic mild to
      moderate aortic stenosis.
AB  - BACKGROUND: Prognostic information for asymptomatic patients with aortic stenosis
      (AS) from prospective studies is scarce and there is no risk score available to
      assess mortality. OBJECTIVES: To develop an easily calculable score, from which
      clinicians could stratify patients into high and lower risk of mortality, using
      data from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. METHOD:
      A search for significant prognostic factors (p<0.01) among SEAS patients was made
      by a combined judgemental and statistical elimination procedure to derive a set
      of three factors (age, gender and smoking) that were forced into the model, and
      four additional factors captured by the data: left-ventricular mass index,
      bilirubin, heart rate and natural logarithm of C reactive protein. Calibration
      was done by comparing observed with calculated number of deaths by tenths of
      calculated risk using coefficients from the simvastatin + ezetimibe group on
      placebo group patients. RESULTS: Discrimination was good with ROC area of 0.76
      for all patients. Estimated probabilities of death were categorised into thirds.
      An optimised split point of estimated 5-year risk was about 15% (close to the
      upper 14% tertile split point), with risk 4 times as high in the upper compared
      to the two lower thirds. The SEAS score performed better than another established
      high risk score developed for other purposes. CONCLUSION: A new seven factor
      model for risk stratification of patients with mild to moderate asymptomatic AS
      identified a high risk group for total mortality with good discrimination
      properties. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT 00092677.

PMID- 22155703
TI  - Have lasers finally found their niche in interventional cardiology?

PMID- 22155704
TI  - Prognostic value of soluble ST2 in an unselected cohort of patients admitted to
      an intensive care unit - The Linz Intensive Care Unit (LICU) study.
AB  - BACKGROUND: Soluble ST2 (sST2) has emerged as a prognostic biomarker in patients
      with heart disease. We tested the hypothesis that sST2 is an independent
      predictor of mortality in patients admitted to an intensive care unit (ICU).
      METHODS: We performed measurements of sST2 plasma concentrations in 530
      consecutive patients admitted to a medical ICU of a tertiary care hospital during
      a study period of one year. The patients recruited during the first six months
      were used for the derivation cohort (n=274) and the patients recruited during the
      second six months were used for the validation cohort (n=256). The endpoint was
      defined as 90-day all-cause mortality. RESULTS: In the derivation cohort, sST2
      was higher among decedents (n=56; median, 146 U/mL) than survivors (n=218; median
      42 U/mL, p<0.001). In multivariate Cox proportional-hazard regression analysis
      (offering age, sex, BMI, APACHE II score, SAPS II, CRP, IL-6, PCT, creatinine,
      total cholesterol, albumin, hs-cTnT, BNP and sST2 as independent variables), sST2
      was a significant predictor of mortality (risk ratio 1.48, 95% CI 1.15-1.90;
      p=0.002 per 1 SD increase in log transformed values). In this statistical model,
      only sST2 and SAPS II contributed independently to mortality prediction. We
      further observed an additive effect of an sST2 plasma concentration of >84 U/mL
      and an increased SAPS II for mortality prediction. The findings from the
      derivation cohort were confirmed in the independent validation cohort. In those
      patients with a length of stay of >48 h at the ICU (n=225), sST2 obtained two
      days after baseline measurement had a better capability than baseline sST2 to
      predict mortality. CONCLUSIONS: In an unselected cohort of patients admitted to
      the ICU, sST2 was an independent predictor of 90-day all-cause mortality and
      added prognostic information to the SAPS II.

PMID- 22155705
TI  - Identification of a Delta6 fatty acid elongase gene for arachidonic acid
      biosynthesis localized to the endoplasmic reticulum in the green microalga
      Myrmecia incisa Reisigl.
AB  - Myrmecia incisa Reisigl H4301 is a green coccoid freshwater microalga that is
      rich in arachidonic acid (20:4n-6, ArA) especially grown under a nitrogen
      starvation stress. A fatty acid elongase gene, MiFAE, was cloned based on a
      selected expressed sequence tag (EST) from a M. incisa cDNA library. To examine
      the function, the MiFAE gene was heterologously expressed in Saccharomyces
      cerevisiae. The fatty acid profile of the transgenic yeast was analyzed by gas
      chromatography-mass spectrometry (GC-MS), and the results illustrated that the
      enzyme encoded by MiFAE was able to elongate gamma-linolenic acid (18:3n-6, GLA)
      and stearidonic acid (18:4n-3, SDA) to di-homo-gamma-linolenic acid (20:3n-6,
      DGLA) and eicosatetraenoic acid (20:4n-3, ETA), respectively, suggesting that the
      cloned MiFAE gene seemed to encode a Delta6 fatty acid elongase. Expression of a
      MiFAE-GFP fusion encoded by a pYES2 vector showed that this Delta6 fatty acid
      elongase localized to the endoplasmic reticulum (ER) of yeast for fatty acid
      elongation. Quantitative real-time PCR results showed that the relative
      transcription level of MiFAE in M. incisa grown under a nitrogen starvation
      stress was increased, but it rapidly declined under conditions of nitrogen
      replenishment. GC-MS analysis revealed that the contents of DGLA, a direct
      product catalyzed by Delta6 fatty acid elongase, and ArA, the terminal product of
      fatty acid biosynthesis in this microalga, increased and decreased accompanying
      the shift from nitrogen starvation to replenishment, although there was a 40h lag
      time for ArA increment. The correlation between the up-regulated and down
      regulated transcription of MiFAE and ArA content in response to a nitrogen
      starvation/replenishment shift showed that nitrogen could regulate the
      transcription of the MiFAE gene and that this gene is critical and responsible
      for the biosynthesis and accumulation of ArA in the cytoplasm of M. incisa.

PMID- 22155706
TI  - The impact of gold nanoparticles on hTERT gene expression leading to termination
      of malignant tumor.
AB  - Cancer nanotechnology is a fascinating field with broad applications in the fight
      against cancer which includes molecular imaging, molecular diagnosis, and
      targeted therapy. One of the emerging field of nanotechnology is applying of
      cancer therapy to specifically target therapeutic agents to tumor cells while
      sparing healthy tissues from harm. Among the many nanomaterials being developed
      in nanomedicine application, gold nano particles have found promising application
      in treatment of cancer because of its unique properties. In this study, we have
      proposed a hypothetical approach to terminate solid tumors using anticancerous
      nanotherapeutic via gold nano particles. These gold nano particles target the
      promoter region of hTERT by stabilizing the G-quadruplex structure and block the
      transcription of 5'-UTR region of hTERT gene.

PMID- 22155707
TI  - Bio-informatics based analysis of genes implicated in alcohol mediated liver
      injury.
AB  - Alcohol induced liver injury has been studied extensively. Using literature
      search and bioinformatics tools, the present study characterizes the genes
      involved in alcohol induced liver injury. The cellular and metabolic processes in
      which genes involved in alcohol induced liver injury are implicated are also
      discussed. The genes related to alcohol induced liver injury are also involved in
      affecting certain molecular functions and metabolism of drugs, besides being
      associated with diseases. In conclusion, the changes in regulation of genes
      implicated in alcohol induced liver injury apart from causing alcohol mediated
      hepatic dysfunction may affect other vital processes in the body.

PMID- 22155708
TI  - The organization of a large transcriptional unit (Fyn) into structural DNA loops
      is cell-type specific and independent of transcription.
AB  - In the interphase nucleus of metazoan cells the DNA is organized in supercoiled
      loops anchored to a nuclear matrix (NM). The DNA is anchored by non-coding
      sequences known as MARs, in situ operationally classified in structural
      constitutive and transient-functional. We have previously shown that the
      organization of the multi-gene rat-albumin family locus into structural DNA loops
      is remarkably different between primary hepatocytes, where such genes are
      expressed, and naive B lymphocytes, where such genes are not expressed. These
      results together with previous observations from other authors suggested that the
      local organization into structural DNA loops might determine the potential for a
      gene to be expressed or not. Thus in the present work we determined the
      organization of the Fyn locus, a single large transcriptional unit, into
      structural DNA loops in both primary rat hepatocytes and B lymphocytes. Our
      results indicate that the organization of the Fyn locus in structural DNA loops
      is cell type-specific and yet the gene is expressed in both cell types,
      supporting the notion that in vivo the organization of DNA into structural loops
      is primarily determined by factors independent of transcription but also that
      transcription adapts to work upon radically different structural DNA loop
      organizations.

PMID- 22155709
TI  - Differential expression of oxidored nitro domain containing protein 1 (NOR1), in
      mouse tissues and in normal and cancerous human tissues.
AB  - Oxidored nitro domain containing protein 1 (NOR1) is usually restrictively
      expressed in the brain and testis. Detection of altered NOR1 expression could
      help us to identify its functions in cell growth, differentiation, metabolism, or
      even carcinogenesis. In this study, NOR1 homologues were identified in multiple
      species through GenBank search. NOR1 is a novel protein conserved in multiple
      species. Mouse NOR1 shared high homology with human NOR1. Furthermore, NOR1
      expression was analyzed in mouse tissues by using RT-PCR, Western blot, and
      immunohistochemistry. The data showed that NOR1 is broadly expressed in neurons
      of mouse brain and the expression profile changes during postnatal development of
      the mouse brain. Moreover, in non-nervous tissues, strong immunostaining for NOR1
      protein was observed in the testis, epididymis and trachea. In addition,
      expression of human NOR1 protein in different normal and cancerous human tissues
      was analyzed via search of the human RNA and protein databases; the data showed
      that although most malignant cells weakly stained or were negative for NOR1
      expression, the liver cancer cells displayed moderate to strong expression of
      NOR1. These data suggested that NOR1 might serve as a cancer/testis/brain antigen
      in cells, and that altered NOR1 expression in liver cancer may help us to
      elucidate the functions of NOR1 protein in liver carcinogenesis.

PMID- 22155711
TI  - Multifractal analysis of HIV-1 genomes.
AB  - Pathogens like HIV-1, which evolve into many closely related variants displaying
      differential infectivity and evolutionary dynamics in a short time scale, require
      fast and accurate classification. Conventional whole genome sequence alignment
      based methods are computationally expensive and involve complex analysis.
      Alignment-free methodologies are increasingly being used to effectively
      differentiate genomic variations between viral species. Multifractal analysis,
      which explores the self-similar nature of genomes, is an alignment-free
      methodology that has been applied to study such variations. However, whether
      multifractal analysis can quantify variations between closely related genomes,
      such as the HIV-1 subtypes, is an open question. Here we address the above by
      implementing the multifractal analysis on four retroviral genomes (HIV-1, HIV-2,
      SIVcpz, and HTLV-1), and demonstrate that individual multifractal properties can
      differentiate between different retrovirus types easily. However, the individual
      multifractal measures do not resolve within-group variations for different known
      subtypes of HIV-1 M group. We show here that these known subtypes can instead be
      classified correctly using a combination of the crucial multifractal measures.
      This method is simple and computationally fast in comparison to the conventional
      alignment-based methods for whole genome phylogenetic analysis.

PMID- 22155710
TI  - INCB38579, a novel and potent histamine H4 receptor small molecule antagonist
      with anti-inflammatory pain and anti-pruritic functions.
AB  - The histamine H4 receptor mediates several histamine-induced cellular functions
      of leukocytes, including cell migration and cytokine production. Recent studies
      suggest that histamine signaling through the histamine H4 receptor can also have
      anti-pruritic and anti-nociceptive functions. 1-(7-(2-amino-6-(4-methylpiperazin
      1-yl) pyrimidin-4-yl)-3, 4-dihdroisoquinolin-2(1H)-yl)-2-cyclopentylethanone
      (INCB38579) is a novel small molecule antagonist of the human and rodent
      histamine H4 receptors with at least 80-fold selectivity over the human histamine
      H1, H2 and H3 receptors, and has good pharmacokinetic properties in rats and
      mice. The compound is potent in inhibiting histamine binding to and signaling
      through the recombinant human, mouse and rat histamine H4 receptors and blocks
      the histamine-induced migration of human and mouse dendritic cells, as well as
      the cell shape change and migration of human eosinophils. INCB38579 and histamine
      may have separate but overlapping binding sites on the human histamine H4
      receptor. This novel inhibitor is efficacious when evaluated in two previously
      established in vivo models for histamine H4 receptor activity (histamine-induced
      itch in mice and carrageenan-induced acute inflammatory pain in rats). When
      examined in formalin-induced pain models, INCB38579 significantly reduces the
      sustained inflammatory pain experienced by rats and mice. A good correlation
      between the protein binding adjusted potency from in vitro studies and its
      analgesic effect in vivo was observed. These results suggest that INCB38579 can
      serve as a useful tool for pharmacologic characterization of the histamine H4
      receptor and further support the hypothesis that targeting the histamine H4
      receptor may provide new therapeutic agents for various chronic inflammatory
      diseases, including inflammatory pain.

PMID- 22155712
TI  - Speciation in an avian complex endemic to the mountains of Middle America
      (Ergaticus, Aves: Parulidae).
AB  - The implementation of the phylogeographic approach for the study of biodiversity
      is critical in poorly sampled regions like the montane systems of Middle America,
      as complex evolutionary histories often result in the presence of independent
      lineages not properly considered by traditional taxonomy. Herein we sequenced
      2370 bp of mtDNA (ND2, cyt b and ATPase) from 81 individuals of Ergaticus, a
      complex of birds endemic to the montane forests of Middle America. Although
      current taxonomy recognizes two species, the results reveal considerable genetic
      structure with the presence of four mtDNA lineages. Two of these lineages within
      Ergaticus ruber evidence the need of a revaluation of the species limits for this
      taxon. The general phylogeographic pattern can be explained as a consequence of
      relative isolation of the populations in different mountain ranges separated by
      low elevation barriers. Most population groups did not show signals of
      demographic expansion with the exception of the one corresponding to clade 1. The
      divergence time estimates point to the Pleistocene as an important time period
      for the diversification of this complex.

PMID- 22155713
TI  - Internal consistency as a method to assess the quality of dating estimates using
      multiple markers.
AB  - Multiple tools are available to infer time in phylogentic reconstructions and
      multiple markers/genes are generally used to obtain more solid reconstructions,
      opening to the issue of which marker performs better in dating. Following the
      observation that multiple markers, applied to the same group of taxa or even to
      the same topology, generally produce different time estimates, we suggest two new
      estimators: DD(jk) to quantify the discordance between two ultrametric dated
      trees with identical topology and ID(j) to quantify the discordance of one tree
      with respect to a study-set of trees in terms of their date estimates.
      Furthermore we suggest a procedure based on a stepwise exclusion algorithm to
      rank trees from the most to the least consistent with the study-set of trees
      based on their time estimates. We name the quality of a tree of having time
      estimates that agree with the majority of other trees as 'internal consistency'.
      We applied this procedure to assess the internal consistency of trees
      individually obtained from 14 mitochondrial markers in 5 insect orders and to
      test whether one or more markers repeatedly produce dates that are more
      consistent. Three genes (nad4, nad5 and cytb) repeatedly perform better than
      others, one (cox2) worse. We suggest this method could be applied in evaluating
      the performance of different markers preliminary to a dating analysis.

PMID- 22155714
TI  - Autotaxin protects microglial cells against oxidative stress.
AB  - Oxidative stress occurs when antioxidant defenses are overwhelmed by oxygen
      reactive species and can lead to cellular damage, as seen in several
      neurodegenerative disorders. Microglia are specialized cells in the central
      nervous system that act as the first and main form of active immune defense in
      the response to pathological events. Autotaxin (ATX) plays an important role in
      the modulation of critical cellular functions, through its enzymatic production
      of lysophosphatidic acid (LPA). In this study, we investigated the potential role
      of ATX in the response of microglial cells to oxidative stress. We show that
      treatment of a microglial BV2 cell line with hydrogen peroxide (H(2)O(2))
      stimulates ATX expression and LPA production. Stable overexpression of ATX
      inhibits microglial activation (CD11b expression) and protects against H(2)O(2)
      treatment-induced cellular damage. This protective effect of ATX was partially
      reduced in the presence of the LPA-receptor antagonist Ki16425. ATX
      overexpression was also associated with a reduction in intracellular ROS
      formation, carbonylated protein accumulation, proteasomal activity, and catalase
      expression. Our results suggest that up-regulation of ATX expression in microglia
      could be a mechanism for protection against oxidative stress, thereby reducing
      inflammation in the nervous system.

PMID- 22155717
TI  - An application of scanning electron microscopy combined with roentgen
      microanalysis (SEM-EDS) in canine urolithiasis.
AB  - Urolithiasis is a common diagnostic and therapeutic problem in small-animal
      veterinary practice. The traditional diagnostic approach usually consists of
      clinical, radiological and ultrasonographic examination of the patient. The main
      diagnostic material is still urine sediment, ignoring the fact that presence of
      crystalluria is not always of pathological significance. In order to establish
      the most effective therapeutic and preventative strategies, especially in the
      case of multicomponent stone, it is crucial to define the exact elemental
      composition of the given stone including crystallization nidus chemical contents.
      In the course of the research, the usefulness of scanning electron microscopy
      combined with X-ray-dispersive spectrometry in analysis of canine mixed and
      compound stones was investigated. The obtained results indicated that the tested
      method allows one to trace the dynamics of the crystallization process, including
      crystallization nucleus detection, and concurrently and quantitatively assess the
      elemental composition of the given urinary concrement. Moreover, the conducted
      research showed epidemiological data of urolithiasis occurrence in a population
      of dogs coming from the southern part of Poland.

PMID- 22155718
TI  - Cytochemical and electron probe X-ray microanalysis studies on the distribution
      change of intracellular calcium in columella cells of soybean roots under
      simulated microgravity.
AB  - The columella cells of soybean roots grown under gravity and simulated
      microgravity induced by a clinostat were examined using potassium pyroantimonate
      (PA) and quantitative X-ray microanalysis of cryosections to determine the role
      of Ca in the regulation of the gravitropic response. Amyloplasts in the columella
      cells were localized exclusively at the bottom under gravity, but diffusely
      distributed in the cytoplasmic matrix under simulated microgravity, thus
      supporting the statolith theory. In the columella cells, PA precipitates
      containing Ca were diffusely distributed in the cytoplasmic matrix under gravity.
      Under simulated microgravity, however, they decreased in number and size in the
      cytoplasmic matrix, whereas increased only in number in the vacuole, indicating
      that Ca moved from the cytoplasmic matrix into the vacuole. The vacuole of
      columella cells contained mostly electron-dense granular structures localized
      along the inner surface of tonoplasts, which closely resembled the tannin vacuole
      reported in Mimosa pulvinar motor cells. Under simulated microgravity, their
      configuration changed dramatically from a granular shape to a flat plate. The
      quantitative X-ray microanalysis of cryosections showed that the vacuolar
      electron-dense structures contained a large amount of Ca. Under simulated
      microgravity, the concentration of Ca increased conspicuously in these vacuolar
      electron-dense structures, concomitantly with a marked decrease of K in the
      vacuoles and an increase of K in the cell walls. These results suggest that the
      release of Ca(2+) from, and uptake by, the vacuolar electron-dense structures is
      closely related to the signal transmission in the gravitropic response and that
      Ca movement occurs opposite to that of K.

PMID- 22155720
TI  - Hsp90 structure and function studied by NMR spectroscopy.
AB  - The molecular chaperone Hsp90 plays a crucial role in folding and maturation of
      regulatory proteins. Key aspects of Hsp90's molecular mechanism and its adenosine
      5'-triphosphate (ATP)-controlled active cycle remain elusive. In particular the
      role of conformational changes during the ATPase cycle and the molecular basis of
      the interactions with substrate proteins are poorly understood. The dynamic
      nature of the Hsp90 machine designates nuclear magnetic resonance (NMR)
      spectroscopy as an attractive method to unravel both the chaperoning mechanism
      and interaction with partner proteins. NMR is particularly suitable to provide a
      dynamic picture of protein-protein interactions at atomic resolution. Hsp90 is
      rather a challenging protein for NMR studies, due to its high molecular weight
      and its structural flexibility. The recent technologic advances allowed
      overcoming many of the traditional obstacles. Here, we describe the different
      approaches that allowed the investigation of Hsp90 using state-of-the-art NMR
      methods and the results that were obtained. NMR spectroscopy contributed to
      understanding Hsp90's interaction with the co-chaperones p23, Aha1 and Cdc37. A
      particular exciting prospect of NMR, however, is the analysis of Hsp90
      interaction with substrate proteins. Here, the ability of this method to
      contribute to the structural characterization of not fully folded proteins
      becomes crucial. Especially the interaction of Hsp90 with one of its natural
      clients, the tumour suppressor p53, has been intensively studied by NMR
      spectroscopy. This article is part of a Special Issue entitled: Heat Shock
      Protein 90 (HSP90).

PMID- 22155719
TI  - Chaperoning steroidal physiology: lessons from mouse genetic models of Hsp90 and
      its cochaperones.
AB  - The molecular chaperone Hsp90 is abundant, ubiquitous, and catholic to biological
      processes in eukaryotes, controlling phosphorylation cascades, protein stability
      and turnover, client localization and trafficking, and ligand-receptor
      interactions. Not surprisingly, Hsp90 does not accomplish these activities alone.
      Instead, an ever-growing number of cochaperones have been identified, leading to
      an explosion of reports on their molecular and cellular effects on Hsp90
      chaperoning of client substrates. Notable among these clients are many members of
      the steroid receptor family, such as glucocorticoid, androgen, estrogen and
      progesterone receptors. Cochaperones typically associated with the mature,
      hormone-competent states of these receptors include p23, the FK506-binding
      protein 52 (FKBP52), FKBP51, protein phosphatase 5 (PP5) and cyclophilin 40
      (Cyp40). The ultimate relevance of these cochaperones to steroid receptor action
      depends on their physiological effects. In recent years, the first mouse genetic
      models of these cochaperones have been developed. This work will review the
      complex and intriguing phenotypes so far obtained in genetically-altered mice and
      compare them to the known molecular and cellular impacts of cochaperones on
      steroid receptors. This article is part of a Special Issue entitled: Heat Shock
      Protein 90 (HSP90).

PMID- 22155721
TI  - Methodological issues in Internet-mediated research: a randomized comparison of
      internet versus mailed questionnaires.
AB  - BACKGROUND: The majority of Internet-mediated studies use measures developed as
      paper-and-pencil measures or face-to-face-delivered material. Previous research
      suggests that the equivalence between online and offline measures must be
      demonstrated rather than assumed. OBJECTIVE: The objective of this study was to
      explore the equivalence 4 measures completed in an online or offline setting.
      METHODS: A sample (n = 1969) were randomly assigned to complete 4 popular scales
      (the SF-12v2, the Hospital Anxiety and Depression Scale (HADS), the Fatigue
      Symptom Inventory, and a single-item fatigue measure) either online or by mail
      survey (pencil and paper). The response rate was 52.51% (n = 1034) and comparable
      between the online and offline groups. RESULTS: Significant differences were
      noted in fatigue levels between the online and offline group (P = .01) as
      measured by the Fatigue Symptom Inventory, with the online sample demonstrating
      higher levels of fatigue. Equivalency was noted for the SF-12v2, the Hospital
      Anxiety and Depression Scale, and the single-item fatigue measure. Internal
      consistency was high except for the SF-12v2. The SF-12v2 may not be an ideal
      measure to use for remote administration. CONCLUSIONS: Equivalency of the
      Hospital Anxiety and Depression Scale (HADS) and the Physical Component Score and
      Mental Component Score of the SF-12v2 for online and offline data were
      demonstrated. Equivalency was not demonstrated for the Fatigue Symptom Inventory.
      Explanations for the difference in fatigue score between the online and offline
      samples are unclear. Research that seeks to match samples and control for
      extraneous online and offline variables is called for, along with exploration of
      factors that may mediate the completion of questionnaires or alter the
      respondents' relationship with the same, to enhance progress in this area.

PMID- 22155722
TI  - Fak depletion in both hematopoietic and nonhematopoietic niche cells leads to
      hematopoietic stem cell expansion.
AB  - Hematopoietic stem cells (HSCs) reside in complex bone marrow microenvironments,
      where niche-induced signals regulate hematopoiesis. Focal adhesion kinase (Fak)
      is a nonreceptor protein tyrosine kinase that plays an essential role in many
      cell types, where its activation controls adhesion, motility, and survival. Fak
      expression is relatively increased in HSCs compared to progenitors and mature
      blood cells. Therefore, we explored its role in HSC homeostasis. We have used the
      Mx1-Cre-inducible conditional knockout mouse model to investigate the effects of
      Fak deletion in bone marrow compartments. The total number as well as the
      fraction of cycling Lin(-)Sca-1(+)c-kit(+) (LSK) cells is increased in Fak(-/-)
      mice compared to controls, while hematopoietic progenitors and mature blood cells
      are unaffected. Bone marrow cells from Fak(-/-) mice exhibit enhanced, long-term
      (i.e., 20-week duration) engraftment in competitive transplantation assays.
      Intrinsic Fak function was assessed in serial transplantation assays, which
      showed that HSCs (Lin(-)Sca-1(+)c-kit(+)CD34(-)Flk-2(-) cells) sorted from Fak(-/
      ) mice have similar self-renewal and engraftment ability on a per-cell basis as
      wild-type HSCs. When Fak deletion is induced after engraftment of Fak(fl/fl)Mx1
      Cre(+) bone marrow cells into wild-type recipient mice, the number of LSKs is
      unchanged. In conclusion, Fak inactivation does not intrinsically regulate HSC
      behavior and is not essential for steady-state hematopoiesis. However, widespread
      Fak inactivation in the hematopoietic system induces an increased and activated
      HSC pool size, potentially as a result of altered reciprocal interactions between
      HSCs and their microenvironment.

PMID- 22155724
TI  - Abortion does not increase mental health problems in women, shows review.

PMID- 22155723
TI  - Hematopoietic stem cell expansion facilitates multilineage engraftment in a
      nonhuman primate cord blood transplantation model.
AB  - The use of umbilical cord blood for allogeneic transplantation has increased
      dramatically over the past years. However, the limited number of cells available
      in a single cord blood unit remains a serious obstacle. Here, we wished to
      establish a nonhuman primate cord blood transplantation model that would allow us
      to test various hematopoietic stem cell expansion and gene therapy strategies. We
      implemented HOXB4-mediated expansion based on our previous experience with HOXB4
      in autologous cells. Cord blood units were divided into two equal parts; half of
      the cells were transduced with a yellow fluorescent protein control vector and
      cryopreserved, and half were transduced with a HOXB4GFP vector, expanded, and
      cryopreserved. Both fractions of cells were transplanted into Macaca nemestrina
      subjects. We found that neutrophil recovery occurred within 19 days in all
      animals, and both neutrophil and platelet recovery were substantially accelerated
      compared to human single unit cord blood transplants. In addition, HOXB4
      transduced and expanded cells resulted in superior engraftment of all
      hematopoietic lineages in all animals over nonexpanded controls. In conclusion,
      we have successfully established a nonhuman primate cord blood transplantation
      model and demonstrated that HOXB4 stimulates expansion and engraftment of
      repopulating cells. The availability of such a model has significant implications
      for developing and testing strategies to improve clinical cord blood
      transplantation, as it will allow comparison of different stem cell expansion
      methodologies within a single animal. Furthermore, it can be used in long-term
      follow-up studies to determine how specific expansion techniques affect
      engraftment of various hematopoietic lineages.

PMID- 22155725
TI  - German health system makes 3.9bn euro surplus in first three quarters of 2011.

PMID- 22155726
TI  - Drug industry is considering more use of differential pricing, conference hears.

PMID- 22155727
TI  - Generation of reactive oxygen species (ROS) is a key factor for stimulation of
      macrophage proliferation by ceramide 1-phosphate.
AB  - We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for
      fibroblasts and macrophages. However, the mechanisms involved in this action were
      only partially described. Here, we demonstrate that C1P stimulates reactive
      oxygen species (ROS) formation in primary bone marrow-derived macrophages, and
      that ROS are required for the mitogenic effect of C1P. ROS production was
      dependent upon prior activation of NADPH oxidase by C1P, which was determined by
      measuring phosphorylation of the p40phox subunit and translocation of p47phox
      from the cytosol to the plasma membrane. In addition, C1P activated cytosolic
      calcium-dependent phospholipase A(2) and protein kinase C-alpha, and NADPH
      oxidase activation was blocked by selective inhibitors of these enzymes. These
      inhibitors, and inhibitors of ROS production, blocked the mitogenic effect of
      C1P. By using BHNB-C1P (a photolabile caged-C1P analog), we demonstrate that all
      of these C1P actions are caused by intracellular C1P. It can be concluded that
      the enzyme responsible for C1P-stimulated ROS generation in bone marrow-derived
      macrophages is NADPH oxidase, and that this enzyme is downstream of PKC-alpha and
      cPLA(2)-alpha in this pathway.

PMID- 22155728
TI  - Phasic contractions of isolated human myometrium are associated with Rho-kinase
      (ROCK)-dependent phosphorylation of myosin phosphatase-targeting subunit (MYPT1).
AB  - Force generation in smooth muscle is driven by phosphorylation of myosin light
      chains (MYL), which is regulated by the equilibrium between the activities of
      myosin light chain kinase (MYLK) and myosin phosphatase (MYLP). MYLK is activated
      by Ca(2+)-calmodulin whereas MYLP is inhibited by phosphorylation of its myosin
      binding subunit (MYPT1) by Ca(2+)-independent mechanisms, leading to generation
      of increased MYL phosphorylation and force for a given intracellular Ca(2+)
      concentration, a phenomenon known as 'calcium-sensitization'. The regulation of
      MYPT1 phosphorylation in human myometrium, which shows increasing phasic
      contractility at the onset of labour, has yet to be fully investigated. Here, we
      explore phosphorylation of MYPT1 at Thr696 and Thr853, alongside phosphorylation
      of MYL, in fresh human myometrial tissue and cultured myometrial cells. We report
      that pMYPT1 (Thr853) levels are dependent on the activity of Rho-associated
      kinase (ROCK), determined using the ROCK inhibitor g-H-1152 and siRNA-mediated
      knockdown of ROCK1/2, and are highly correlated to ppMYL (Thr18/Ser19) levels.
      Pharmacological inhibition of ROCK was associated with a decrease in oxytocin
      (OXT)-stimulated contractility of myometrial strips in vitro. Moreover, we have
      measured pMYPT1 and pMYL levels between and during spontaneous and OXT-stimulated
      phasic contractions by rapidly freezing contracting muscle, and demonstrate for
      the first time functional coupling between increases in pMYPT1 (Thr853), ppMYL
      (Thr18/Ser19) and phasic contractility that is ROCK-dependent. The combined
      approach of measuring contractility and phosphorylation has demonstrated that the
      phosphorylation of MYPT1 (Thr853) changes dynamically with each contraction and
      has elucidated a defined role for ROCK in regulating myometrial contractility
      through MYLP, providing new insights into uterine physiology which will stimulate
      further research into treatments for preterm labour.

PMID- 22155729
TI  - Embryo collection induces transient activation of XBP1 arm of the ER stress
      response while embryo vitrification does not.
AB  - Embryo cryopreservation has become a standard procedure in the practice of
      assisted reproduction. While routinely performed in IVF labs, the effects of
      embryo vitrification on the molecular mechanisms governing preimplantation
      development remain largely unknown. The endoplasmic reticulum stress (ER stress)
      response is an evolutionary conserved mechanism that cells employ to manage ER
      stress. ER stress can be defined as an imbalance between protein synthesis and
      secretion within the ER. The primary focus of this study was to investigate
      whether standard embryo manipulations, including embryo collection, culture and
      vitrification, result in activation of the ER stress pathway in vitro and to
      determine whether the embryo utilizes the unfolded protein response as an
      adaptive response. Our results indicate that the major ER stress pathway
      constituents are present at all stages of preimplantation development and that
      the activation of ER stress pathways can be induced at the 8-cell, morula and
      blastocyst stages. Additionally, we have demonstrated that the IRE1alpha arm of
      the ER Stress pathway is activated in freshly collected embryos but
      contrastingly, this ER Stress arm is not activated following embryo
      vitrification. It is important to understand the possible stresses that Assisted
      Reproductive Technologies place on the embryo and the mechanisms the embryo
      employs to adapt to these stresses. This study indicates that among the adaptive
      pathways available, cultured mammalian embryos can employ the ER stress pathway.
      Assisted reproduction techniques should be aware that their activities may induce
      the ER stress pathway in their patients' early embryos.

PMID- 22155730
TI  - Extensive right pulmonary artery dissection in a young patient with chronic
      pulmonary hypertension.

PMID- 22155731
TI  - Synovial fluid CD34- CD44+ CD90+ mesenchymal stem cell levels are associated with
      the severity of primary knee osteoarthritis.
AB  - To the best of our knowledge, no reports have directly compared synovial fluid
      (SF)- and synovial membrane (SM)-derived mesenchymal stem cells (MSCs) from
      primary knee osteoarthritis patients in terms of MSC proportion, either
      immediately after isolation or during culture. Any possible correlation between
      SM- and SF-MSC purity and osteoarthritis severity, also remains unclear. We
      therefore assessed quantitative and phenotypic differences in MSCs isolated from
      SF and SM. We also evaluated the correlation between sample MSC purity, and
      disease severity, in patients with osteoarthritis. The main result of the current
      study was that the mean SF-MSC proportion at passage 0 was negatively correlated
      with Kellgren-Lawrence (KL) grade (r = -0.565, P = 0.002). In addition, KL grade
      was a only significant independent negative predictor of SF-MSC proportion at
      passage 0 (beta = -0.356, P = 0.039). Conclusively, the proportion of SF-MSCs in
      fresh samples, evaluated at the single cell level, was inversely correlated with
      osteoarthritis severity.

PMID- 22155732
TI  - Phylogenetic analysis of mitochondrial outer membrane beta-barrel channels.
AB  - Transport of molecules across mitochondrial outer membrane is pivotal for a
      proper function of mitochondria. The transport pathways across the membrane are
      formed by ion channels that participate in metabolite exchange between
      mitochondria and cytoplasm (voltage-dependent anion-selective channel, VDAC) as
      well as in import of proteins encoded by nuclear genes (Tom40 and Sam50/Tob55).
      VDAC, Tom40, and Sam50/Tob55 are present in all eukaryotic organisms, encoded in
      the nuclear genome, and have beta-barrel topology. We have compiled data sets of
      these protein sequences and studied their phylogenetic relationships with a
      special focus on the position of Amoebozoa. Additionally, we identified these
      protein-coding genes in Acanthamoeba castellanii and Dictyostelium discoideum to
      complement our data set and verify the phylogenetic position of these model
      organisms. Our analysis show that mitochondrial beta-barrel channels from
      Archaeplastida (plants) and Opisthokonta (animals and fungi) experienced many
      duplication events that resulted in multiple paralogous isoforms and form well
      defined monophyletic clades that match the current model of eukaryotic evolution.
      However, in representatives of Amoebozoa, Chromalveolata, and Excavata (former
      Protista), they do not form clearly distinguishable clades, although they locate
      basally to the plant and algae branches. In most cases, they do not posses
      paralogs and their sequences appear to have evolved quickly or degenerated.
      Consequently, the obtained phylogenies of mitochondrial outer membrane beta
      channels do not entirely reflect the recent eukaryotic classification system
      involving the six supergroups: Chromalveolata, Excavata, Archaeplastida,
      Rhizaria, Amoebozoa, and Opisthokonta.

PMID- 22155734
TI  - Model-free free energy for voltage-gated channels.

PMID- 22155733
TI  - Changes in gene expression associated with reproductive maturation in wild female
      baboons.
AB  - Changes in gene expression during development play an important role in shaping
      morphological and behavioral differences, including between humans and nonhuman
      primates. Although many of the most striking developmental changes occur during
      early development, reproductive maturation represents another critical window in
      primate life history. However, this process is difficult to study at the
      molecular level in natural primate populations. Here, we took advantage of
      ovarian samples made available through an unusual episode of human-wildlife
      conflict to identify genes that are important in this process. Specifically, we
      used RNA sequencing (RNA-Seq) to compare genome-wide gene expression patterns in
      the ovarian tissue of juvenile and adult female baboons from Amboseli National
      Park, Kenya. We combined this information with prior evidence of selection
      occurring on two primate lineages (human and chimpanzee). We found that in cases
      in which genes were both differentially expressed over the course of ovarian
      maturation and also linked to lineage-specific selection this selective signature
      was much more likely to occur in regulatory regions than in coding regions. These
      results suggest that adaptive change in the development of the primate ovary may
      be largely driven at the mechanistic level by selection on gene regulation,
      potentially in relationship to the physiology or timing of female reproductive
      maturation.

PMID- 22155735
TI  - An extracellular domain of the accessory beta1 subunit is required for modulating
      BK channel voltage sensor and gate.
AB  - A family of tissue-specific auxiliary beta subunits modulates large conductance
      voltage- and calcium-activated potassium (BK) channel gating properties to suit
      their diverse functions. Paradoxically, beta subunits both promote BK channel
      activation through a stabilization of voltage sensor activation and reduce BK
      channel openings through an increased energetic barrier of the closed-to-open
      transition. The molecular determinants underlying beta subunit function,
      including the dual gating effects, remain unknown. In this study, we report the
      first identification of a beta1 functional domain consisting of Y74, S104, Y105,
      and I106 residues located in the extracellular loop of beta1. These amino acids
      reside within two regions of highest conservation among related beta1, beta2, and
      beta4 subunits. Analysis in the context of the Horrigan-Aldrich gating model
      revealed that this domain functions to both promote voltage sensor activation and
      also reduce intrinsic gating. Free energy calculations suggest that the dual
      effects of the beta1 Y74 and S104-I106 domains can be largely accounted for by a
      relative destabilization of channels in open states that have few voltage sensors
      activated. These results suggest a unique and novel mechanism for beta subunit
      modulation of voltage-gated potassium channels wherein interactions between
      extracellular beta subunit residues with the external portions of the gate and
      voltage sensor regulate channel opening.

PMID- 22155736
TI  - Estimating the voltage-dependent free energy change of ion channels using the
      median voltage for activation.
AB  - Voltage-gated ion channels are crucial for electrical activity and chemical
      signaling in a variety of cell types. Structure-activity studies involving
      electrophysiological characterization of mutants are widely used and allow us to
      quickly realize the energetic effects of a mutation by measuring macroscopic
      currents and fitting the observed voltage dependence of conductance to a
      Boltzmann equation. However, such an approach is somewhat limiting, principally
      because of the inherent assumption that the channel activation is a two-state
      process. In this analysis, we show that the area delineated by the gating charge
      displacement curve and its ordinate axis is related to the free energy of
      activation of a voltage-gated ion channel. We derive a parameter, the median
      voltage of charge transfer (V(m)), which is proportional to this area, and prove
      that the chemical component of free energy change of a system can be obtained
      from the knowledge of V(m) and the maximum number of charges transferred. Our
      method is not constrained by the number or connectivity of intermediate states
      and is applicable to instances in which the observed responses show a multiphasic
      behavior. We consider various models of ion channel gating with voltage-dependent
      steps, latent charge movement, inactivation, etc. and discuss the applicability
      of this approach in each case. Notably, our method estimates a net free energy
      change of approximately -14 kcal/mol associated with the full-scale activation of
      the Shaker potassium channel, in contrast to -2 to -3 kcal/mol estimated from a
      single Boltzmann fit. Our estimate of the net free energy change in the system is
      consistent with those derived from detailed kinetic models (Zagotta et al. 1994.
      J. Gen. Physiol. doi:10.1085/jgp.103.2.321). The median voltage method can
      reliably quantify the magnitude of free energy change associated with activation
      of a voltage-dependent system from macroscopic equilibrium measurements. This
      will be particularly useful in scanning mutagenesis experiments.

PMID- 22155737
TI  - Aberrant expression of the transcriptional factor Twist1 promotes invasiveness in
      ALK-positive anaplastic large cell lymphoma.
AB  - The transcriptional factor Twist1 has been shown to play a key role in regulating
      epithelial mesenchymal transition, invasiveness and migratory properties in solid
      tumors. We found that Twist1 is aberrantly expressed in ALK-positive anaplastic
      large cell lymphoma (ALK+ALCL), a type of T-cell lymphoid malignancy. Using RT
      PCR and Western blots, Twist1 was detectable in all 3 ALK+ALCL cell lines
      examined but absent in normal T-cells. By immunohistochemistry, Twist1 was
      detectable in all 10 cases of ALK+ALCL examined; benign lymphoid tissues were
      consistently negative. Twist1 expression in ALK+ALCL cells can be attributed to
      the NPM-ALK/STAT3 signaling axis, the key oncogenic driving force in this tumor
      type. Twist1 is biologically important in ALK+ALCL cells, as Twist1 knockdown
      resulted in a significant decrease in their invasiveness in an in-vitro assay.
      Further investigation revealed that this increase in invasiveness is linked to
      the activation of AKT and down-regulation of p66Shc, two signaling proteins known
      to be involved in NPM-ALK-mediated oncogenesis. Lastly, knockdown of Twist1
      sensitizes ALK+ALCL cells to the growth inhibitory effect of PF-2341066
      (Crizotinib(r)), an ALK inhibitor being used in clinical trials. In conclusion,
      Twist1 expression, owing to the abnormal NPM-ALK/STAT3 signaling, contributes to
      its invasiveness and decreased sensitivity to PF-2341066 in ALK+ALCL.

PMID- 22155738
TI  - A holistic framework to improve the uptake and impact of eHealth technologies.
AB  - BACKGROUND: Many eHealth technologies are not successful in realizing sustainable
      innovations in health care practices. One of the reasons for this is that the
      current development of eHealth technology often disregards the interdependencies
      between technology, human characteristics, and the socioeconomic environment,
      resulting in technology that has a low impact in health care practices. To
      overcome the hurdles with eHealth design and implementation, a new, holistic
      approach to the development of eHealth technologies is needed, one that takes
      into account the complexity of health care and the rituals and habits of patients
      and other stakeholders. OBJECTIVE: The aim of this viewpoint paper is to improve
      the uptake and impact of eHealth technologies by advocating a holistic approach
      toward their development and eventual integration in the health sector. METHODS:
      To identify the potential and limitations of current eHealth frameworks (1999
      2009), we carried out a literature search in the following electronic databases:
      PubMed, ScienceDirect, Web of Knowledge, PiCarta, and Google Scholar. Of the 60
      papers that were identified, 44 were selected for full review. We excluded those
      papers that did not describe hands-on guidelines or quality criteria for the
      design, implementation, and evaluation of eHealth technologies (28 papers). From
      the results retrieved, we identified 16 eHealth frameworks that matched the
      inclusion criteria. The outcomes were used to posit strategies and principles for
      a holistic approach toward the development of eHealth technologies; these
      principles underpin our holistic eHealth framework. RESULTS: A total of 16
      frameworks qualified for a final analysis, based on their theoretical backgrounds
      and visions on eHealth, and the strategies and conditions for the research and
      development of eHealth technologies. Despite their potential, the relationship
      between the visions on eHealth, proposed strategies, and research methods is
      obscure, perhaps due to a rather conceptual approach that focuses on the
      rationale behind the frameworks rather than on practical guidelines. In addition,
      the Web 2.0 technologies that call for a more stakeholder-driven approach are
      beyond the scope of current frameworks. To overcome these limitations, we
      composed a holistic framework based on a participatory development approach,
      persuasive design techniques, and business modeling. CONCLUSIONS: To demonstrate
      the impact of eHealth technologies more effectively, a fresh way of thinking is
      required about how technology can be used to innovate health care. It also
      requires new concepts and instruments to develop and implement technologies in
      practice. The proposed framework serves as an evidence-based roadmap.

PMID- 22155739
TI  - Sequence diversity in haloalkane dehalogenases, as revealed by PCR using family
      specific primers.
AB  - Haloalkane dehalogenases (HLDs) are hydrolytic enzymes that cleave carbon-halogen
      bonds in various halogenated compounds. Interest initially grew in HLDs as
      biocatalysts for bioremediation and later for biotransformation applications;
      each specific HLD within the HLD family has its own substrate specificity,
      enantioselectivity and product inhibition characteristics. We developed
      degenerate oligonucleotide primers for HLD-encoding genes and used these to PCR
      amplify large hld gene fragments using genomic DNA from the microbial community
      of a chlorinated-solvent-contaminated aquifer as a template. An analysis of small
      subunit ribosomal RNA genes revealed a high complexity in the eubacterial
      population, dominated by alpha-, beta- and gamma-Proteobacteria, and
      Acidobacteria. Using HLD-family-specific primers, we also retrieved transcribed
      hld homologues from the microbial consortium of this contaminated site. The DNA
      derived hld sequences were phylogenetically broadly distributed over both HLD
      subclasses I and II. Most hld sequences of the environmental RNA data set
      clustered in three groups within both HLD subclasses, indicating that a
      considerable proportion of the microbial consortium carrying hld genes was
      actively involved in haloalkane dehalogenation. The small sequence variation in
      hld genes and transcripts within each HLD cluster inferred the presence of a
      substantial pool of highly related HLD genes. The sequence variability appeared
      to be unevenly distributed over the HLD genes, however, with no apparent
      preference for a particular protein segment or domain.

PMID- 22155740
TI  - Parthenolide, an inhibitor of the nuclear factor-kappaB pathway, ameliorates
      dextran sulfate sodium-induced colitis in mice.
AB  - BACKGROUND: Activation of nuclear factor-kappa B (NF-kappaB), which controls
      transcription of various pro-inflammatory cytokine genes, has been shown to play
      a critical role in the pathogenesis of ulcerative colitis (UC). Parthenolide, a
      sesquiterpene lactone compound isolated from extracts of the herb Feverfew
      (Tanacetum parthenium), has been demonstrated to be a potent inhibitor of NF
      kappaB activation. This study was designed to investigate the effects of
      parthenolide on an experimental murine colitis model. MATERIALS AND METHODS:
      Experimental colitis was induced by dextran sulfate sodium (DSS), and mice were
      divided into 3 groups: normal control, DSS+saline, and DSS+parthenolide. The
      disease activity index (DAI) and histological score were observed. The tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels were measured by
      enzyme-linked immunosorbent assay. Phospho-IkappaBalpha, IkappaBalpha and phospho
      NF-kappaB p65 expression were assessed by western blot analysis. Myeloperoxidase
      (MPO) activity was determined by using MPO assay kit. RESULTS: Administration of
      parthenolide significantly reduced the severity of DSS-induced colitis as
      assessed by DAI and histological score, and resulted in downregulation of MPO
      activity and phospho-NF-kappaB p65 expression by the blockade of phosphorylation
      and subsequent degradation of IkappaB protein, strikingly reduced the production
      of TNF-alpha and IL-1beta. CONCLUSION: Parthenolide exerts beneficial effects in
      experimental colitis and may therefore provide a useful therapeutic approach for
      the treatment of UC.

PMID- 22155741
TI  - Lycorine inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in
      RAW264.7 cells through suppressing P38 and STATs activation and increases the
      survival rate of mice after LPS challenge.
AB  - As a natural alkaloid extracted from Amaryllidaceae, lycorine shows various
      biological effects on tumor cells. Here we show that lycorine dose-dependently
      inhibited the LPS-induced up-regulation of nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) protein level in RAW264.7 cells. Besides, it also
      inhibited NO, PGE(2), TNF-alpha and IL-6 release from LPS-treated RAW264.7 cells.
      RT-PCR experiments showed that lycorine suppressed LPS-induced iNOS but not COX-2
      gene expression. Moreover, lycorine decreased LPS-induced mortality in mice.
      Mechanistically, LPS-induced activation of P38 and STATs pathways was suppressed
      significantly by lycorine. In addition, lycorine did not interfere with the
      phosphorylation of ERK1/2, JNK1/2 and NF-kappaB pathways. In conclusion, lycorine
      inhibits LPS-induced production of pro-inflammatory mediators and increases the
      survival rate of mice after LPS challenge, suggesting that lycorine could play an
      anti-inflammatory role in response to LPS.

PMID- 22155743
TI  - The MPTP neurotoxic lesion model of Parkinson's disease activates the
      apolipoprotein E cascade in the mouse brain.
AB  - Apolipoprotein E (apoE) is recognized as a key actor in brain remodeling. It has
      been shown to increase after peripheral and central injury, to modulate
      reparative capacity in neurodegenerative conditions like Alzheimer's disease (AD)
      and to be associated with a number of other neurodegenerative diseases. This
      particular function of apoE has been postulated to underlie the robust
      association with risk and age at onset of AD. ApoE associations studies with
      Parkinson's disease (PD), the second most prevalent neurodegenerative disease,
      have generated contradictory results but associations with age at onset and
      dementia in PD stand out. We investigate here whether apoE is involved in
      response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
      degeneration that models PD-like deafferentation of the striatum in the mouse and
      participates in compensatory reinnervation mechanisms. We examined the
      modifications in gene expression and protein levels of apoE and its key
      receptors, the low density lipoprotein receptor (LDLR) and the LDLR-related
      protein (LRP), as well as the reactive astrocyte marker glial fibrillary acidic
      protein (GFAP) in different brain structures throughout the degenerative and
      reactive regenerative period. In the striatum, upregulations of GFAP, apoE and
      LRP mRNAs at 1 day post-treatment were associated with marked decreases in
      dopamine (DA) levels, loss in tyrosine hydroxylase protein content, as well as to
      a compensatory increase in dopaminergic metabolism. Subsequent return to near
      control levels coincided with indications of reinnervation in the striatum: all
      consistent with a role of apoE during the degenerative process and regenerative
      period. We also found that this cascade was activated in the hippocampus and more
      so than in the striatum, with a particular contribution of LDLR expression. The
      hippocampal activation did not correlate with substantial neurochemical
      reductions but appears to reflect local subtle alteration of DA metabolism and
      the regulation of plasticity-related event in this structure. This study provides
      first evidence of an activation of the apoE/apoE receptors cascade in a mouse
      model of PD, specifically in the MPTP-induced deafferentation of the striatum.
      Results are also quite consistent with the postulated role of apoE in brain
      repair but, raise the issue of possible lesion- and region-specific alterations
      in gene expression.

PMID- 22155744
TI  - A novel imidazopyridine analogue as a phosphatidylinositol 3-kinase inhibitor
      against human breast cancer.
AB  - Potentiation of anti-breast cancer activity of an imidazopyridine-based PI3Kalpha
      inhibitor, HS-104, was investigated in human breast cancer cells. HS-104 shows
      strong inhibitory activity against recombinant PI3Kalpha isoform and the PI3K
      signaling pathway, resulting in anti-proliferative activity in breast cancer
      cells. It also induced cell cycle arrest at the G(2)/M phase as well as
      apoptosis. Furthermore, oral administration of HS-104 significantly inhibited the
      growth of tumor in SkBr3 mouse xenograft models. Therefore, HS-104 could be
      considered as a potential candidate for the treatment of human breast cancer.

PMID- 22155745
TI  - Survivin isoform Delta Ex3 regulates tumor spheroid formation.
AB  - Survivin is an important member of the Inhibitor of Apoptosis Proteins (IAPs)
      family and has essential roles in apoptosis and cell cycle progression. This gene
      is commonly upregulated in human cancer and provides an exciting diagnostic and
      therapeutic target. Survivin is expressed as several isoforms that are generated
      by alternative splicing, and some of these present antagonistic activities.
      Currently, information regarding the regulation of these isoforms is lacking. In
      this study, we sought to analyze survivin Delta Ex3 expression in a three
      dimensional model of avascular tumors and its overexpression effects in processes
      such as proliferation, clonogenicity and apoptosis. We found a positive
      correlation between spheroid growth and survivin Delta Ex3 expression during the
      exponential phase. We demonstrated that this isoform not only decreased apoptosis
      but also inhibited tumor spheroid formation by decreasing proliferation and
      clonogenic survival. These results point toward a dual and antagonistic effect of
      this spliced survivin isoform in cancer development.

PMID- 22155746
TI  - WikiBuild: a new application to support patient and health care professional
      involvement in the development of patient support tools.
AB  - Active patient and public involvement as partners in their own health care and in
      the development of health services is key to achieving a health care system that
      is responsive to patients' needs and values. It promotes better use of the health
      care system, and improves health outcomes, quality of life and patient
      satisfaction. By involving patients and health care professionals as partners in
      the creation and updating of patient health support tools, wikis--highly
      accessible, interactive vehicles of communication--have the potential to empower
      users to implement these support tools in daily life. Acknowledging the potential
      of wikis, and recognizing that they capitalize on the free and open access to
      information, scientists, opinion leaders and patient advocates have suggested
      that wikis could help decision-making constituencies improve the delivery of
      health care. They might also decrease its cost and improve access to knowledge
      within developing countries. However, little is known about the efficacy of wikis
      in helping to attain these goals. There is also a need to know more about the
      intention of patients and health care workers to use wikis, in what circumstances
      and what factors will influence their use of wikis. In this issue of the Journal
      of Medical Internet Research, Gupta et al describe how they developed and tested
      a new wiki-inspired application to improve asthma care. The researchers involved
      patients with asthma, primary care physicians, pulmonologists and certified
      asthma educators in the construction of an asthma action plan. Their paper-
      entitled "WikiBuild: a new online collaboration process for multistakeholder tool
      development and consensus building"--is the first description of a wiki-inspired
      technology built to involve patients and health care professionals in the
      development of a patient support tool. This innovative study has made important
      contributions toward how wikis could be generalized to involve multiple
      stakeholders in the development of other knowledge translation tools such as
      clinical practice guidelines or decision aids. More specifically, Gupta et al
      have uncovered potential action mechanisms toward increasing usage of these tools
      by patients and health care professionals. These are decreasing hierarchical
      influences, increasing usability and adapting a tool to local context. More
      research is now needed to determine if the use of the resulting wiki-developed
      plan will actually be higher than a plan developed using other methods.
      Furthermore, there is also a need to assess the intention of participants to
      continue using wiki-based processes on an ongoing basis. It is in this dynamic
      and continuous retroaction loop that the support tool users--both patients and
      health care professionals--can adapt and improve the product after its real-life
      shortcomings are revealed and as new evidence becomes available. As such, a wiki
      would be more than a simple patient support development tool, but could also
      become a dynamic and interactive repository and delivery tool that would
      facilitate ongoing and sustainable patient and professional engagement.

PMID- 22155747
TI  - Soybean agglutinin coated PLA particles entrapping candidate vaccines induces
      enhanced primary and sustained secondary antibody response from single point
      immunization.
AB  - Polylactide (PLA) polymer particles entrapping diphtheria toxoid (DT) or tetanus
      toxoid (TT) were formulated with surface coatings of soybean agglutinin to have
      dendritic cells (DCs) targeting ability through c-type lectin receptors (CLR). It
      was observed that soybean agglutinin coating resulted in more association of
      polymer particles with DCs. Immunization with soybean agglutinin coated polymer
      particles entrapping DT or TT elicited antibody response better than the plain
      particles entrapping antigens. Both for TT and DT, single point immunization of
      soybean agglutinin coated polymer particles along with alum resulted in very high
      antibody titers; much higher than that observed while immunizing with alum
      adsorbed antigens or admixture of particle entrapped antigens and alum. More
      interestingly, single point immunization with soybean agglutinin coated polymer
      particles also elicited very high secondary antibody response which sustained for
      more than six weeks in mice. Interactions of different polymeric microparticles
      formulations with DCs correlated with antibody response. Improved primary and
      sustained secondary antibody response from single point immunization of antigen
      entrapped soybean agglutinin coated particles was attributed to the N-linked
      glycan mediated targeting of polymer particles to DCs.

PMID- 22155748
TI  - A p.R369G POLG2 mutation associated with adPEO and multiple mtDNA deletions
      causes decreased affinity between polymerase gamma subunits.
AB  - Human mitochondrial DNA (mtDNA) polymerase gamma (pol gamma) is the sole enzyme
      required to replicate and maintain the integrity of the mitochondrial genome. It
      comprises two subunits, a catalytic p140 subunit and a smaller p55 accessory
      subunit encoded by the POLG2 gene. We describe the molecular characterization of
      a potential dominant POLG2 mutation (p.R369G) in a patient with adPEO and
      multiple mtDNA deletions. Biochemical studies of the recombinant mutant p55
      protein showed a reduced affinity to the pol gamma p140 subunit, leading to
      impaired processivity of the holoenzyme complex but did not show sensitivity to N
      ethylmalaimide (NEM) inhibition, inferring a novel disease mechanism.

PMID- 22155749
TI  - Establishing a national register of occupational doses based on the IAEA
      regulatory authority information system (RAIS).
AB  - IAEA Safety Standards require countries to establish and maintain registers of
      occupational doses. This paper demonstrates a possibility of the use of the
      regulatory authority information system (RAIS) for this purpose. A two-level
      classification scheme for work activities, based on UNSCEAR categorisation, is
      adopted. The implementation approach presented in this paper covers all types of
      occupational exposure to artificial as well as to natural sources of ionising
      radiation. Although the presented model is general, it can be adjusted to
      specific national needs by simply changing certain settings or making use of the
      extensive RAIS customisation capabilities.

PMID- 22155750
TI  - Assessment of doses and risk due to natural radionuclides in edible biota of
      Domiasiat, Meghalaya.
AB  - A radiation dose assessment exercise was carried out for the edible biota Solanum
      nigrum, Carica papaya, Raphnus sativum and Phaseolus domesticus due to naturally
      available radionuclides (40)K, (238)U and (232)Th in the Domiasiat area in
      Meghalaya, India. The concentration of radionuclides in biota and corresponding
      soil was measured by the NaI(Tl) detector having a minimum detection limit
      (efficiency, 32.4%) and machine counting time of 3000 s. The obtained transfer
      factor for (40)K was 0.3061, 0.7163, 0.1988 and 0.1279, for (232)Th 0.0003, 2.22E
      05, 2.71E-05 and 3.45E-05 and for (238)U 1.46E-05, 9.73E-05, 1.46E-05 and 3.11E
      05 (ratio) in each biota, respectively. The detailed physiological and
      morphological study of the biota was carried out. The point source dose
      distribution (source<->target) hypothesis was applied for the radiation absorbed
      fraction. The generated data were modelled using FASSET and obtained un-weighted
      total dose was 1.78E-04, 6.84E-03, 8.46E-03 and 1.73E-04 MUGy h(-1),
      respectively, finally compared with the IAEA and UNSCEAR data set for screening
      level dose risk assessment.

PMID- 22155751
TI  - On measurements and models.

PMID- 22155752
TI  - Proton and iron ion observations from a solid-state microdosimeter.
AB  - The tissue equivalent proportional counter (TEPC) that utilises a gas cavity has
      been the standard to obtain microdosimetric observations. An alternative is the
      solid-state microdosimeter that replaces the gas with a solid-state detector with
      microscopic sensitive volumes. Here, we describe the development of two versions
      of a personal solid-state microdosimeter for space exploration applications and
      give test results for iron and proton beams with comparisons to TEPC measurements
      and Geant4 radiation transport code simulations. In addition, we describe and
      provide test results of an optical technique to carry out an end-to-end system
      test and calibration of a silicon solid-state microdosimeter. This technique
      eliminates the need for an ionising radiation source with its attendant issues on
      use and transportation and provides an advantage over the TEPC.

PMID- 22155753
TI  - Comparison of computed tomography dose reporting software.
AB  - Computed tomography (CT) dose reporting software facilitates the estimation of
      doses to patients undergoing CT examinations. In this study, comparison of three
      software packages, i.e. CT-Expo (version 1.5, Medizinische Hochschule, Hannover,
      Germany), ImPACT CT Patients Dosimetry Calculator (version 0.99*, Imaging
      Performance Assessment on Computed Tomography, www.impactscan.org) and WinDose
      (version 2.1a, Wellhofer Dosimetry, Schwarzenbruck, Germany), has been made in
      terms of their calculation algorithm and the results of calculated doses.
      Estimations were performed for head, chest, abdominal and pelvic examinations
      based on the protocols recommended by European guidelines using single-slice CT
      (SSCT) (Siemens Somatom Plus 4, Erlangen, Germany) and multi-slice CT (MSCT)
      (Siemens Sensation 16, Erlangen, Germany) for software-based female and male
      phantoms. The results showed that there are some differences in final dose
      reporting provided by these software packages. There are deviations of effective
      doses produced by these software packages. Percentages of coefficient of variance
      range from 3.3 to 23.4 % in SSCT and from 10.6 to 43.8 % in MSCT. It is important
      that researchers state the name of the software that is used to estimate the
      various CT dose quantities. Users must also understand the equivalent
      terminologies between the information obtained from the CT console and the
      software packages in order to use the software correctly.

PMID- 22155754
TI  - Capsule endoscopy is not as accurate as esophagogastroduodenoscopy in screening
      cirrhotic patients for varices.
AB  - BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) is the standard technique for
      screening cirrhotic patients for high-risk varices and other significant upper
      gastrointestinal lesions (HRVLs). We investigated whether esophageal capsule
      endoscopy (ECE) is as convenient and accurate as EGD for the detection of HRVLs.
      METHODS: We analyzed data from 65 cirrhotic patients without prior upper
      gastrointestinal bleeding who were examined for varices and HRVLs by ECE and EGD
      (both procedures were performed on the same day). EGD was performed by 2
      physicians (75% of patients were unsedated) who used standard grading for
      esophageal and gastric varices, portal hypertensive gastropathy, and HRVLs. Coded
      capsule tracings were read by 2 investigators, blinded to the EGD findings, using
      standard grading. RESULTS: The median procedure time for EGD (with or without
      biopsy collection) was 3 minutes, compared with 20 minutes for ECE. The overall
      accuracy for diagnosis of esophageal varices was 63.2% +/- 5.9%; for detection of
      esophageal varices red marks was 68.8% +/- 5.4%; and for diagnosis of other HRVLs
      was 51.5% +/- 4.2%. The interobserver agreement in the diagnosis of esophageal
      varices was 90.8%; in the detection of esophageal varices red marks was 86.2%;
      and in the diagnosis of other HRVLs was 7.3%. CONCLUSIONS: ECE is not as accurate
      as EGD in the diagnosis of esophageal varices and red markings or in grading
      esophageal varices. Moreover, ECE had poor accuracy in grading portal
      hypertensive gastropathy and detecting ulcers, gastric varices, and other
      significant upper gastrointestinal lesions. It took significantly longer to
      perform ECE and interpret the results than for EGD. These findings do not support
      ECE as a preferred tool for screening esophageal varices and HRVLs.

PMID- 22155756
TI  - Adenocarcinoma complicating ulcerative colitis presenting as multiple pseudopolyp
      like lesions.

PMID- 22155755
TI  - Induction and maintenance therapy with infliximab for children with moderate to
      severe ulcerative colitis.
AB  - BACKGROUND & AIMS: We evaluated the efficacy and safety of infliximab for
      inducing and maintaining benefit in children with moderately to severely active
      ulcerative colitis (UC). METHODS: Patients (6-17 years old) who had active UC
      (Mayo scores of 6-12; endoscopic subscores >= 2) and had not responded to or
      tolerated conventional treatment were given 5 mg/kg infliximab at weeks 0, 2, and
      6. The primary end point was response at week 8 (decreases in Mayo scores >= 30%
      and >= 3 points and decreases in rectal bleeding subscores of >= 1 or an absolute
      subscore of <= 1). At week 8, only responders were randomly assigned to groups
      given infliximab every 8 or 12 weeks (q8w or q12w) and followed through week 54.
      Maintenance end points included pediatric UC activity index scores <10 points,
      defined as remission. RESULTS: At week 8, infliximab induced a response in 73.3%
      of patients (44 of 60) (95% confidence interval, 62.1%-84.5%; a positive result
      was defined by 95% confidence interval lower limit >40%). Among responders, twice
      as many were in remission at week 54 after q8w (8 of 21, 38.1%) than q12w (4 of
      22, 18.2%; P = .146) therapy. Assuming the q8w remission rate for responders, the
      overall remission rate at week 54 would be 28.6%. Serious adverse events and
      infusion reactions occurred in similar proportions in the q8w and q12w groups. No
      deaths, malignancies, opportunistic infections, tuberculosis, or delayed
      hypersensitivity reactions were reported. CONCLUSIONS: Infliximab was safe and
      effective, inducing a response at week 8 in 73.3% of pediatric patients with
      moderate to severely active UC who did not respond to conventional therapy. The
      overall remission rate at week 54 for all enrolled patients was 28.6%, assuming
      the more effective q8w remission rate.

PMID- 22155757
TI  - Taxonomy of the family Halobacteriaceae: a paradigm for changing concepts in
      prokaryote systematics.
AB  - The halophilic Archaea of the family Halobacteriaceae (36 genera with 129 species
      with standing in nomenclature as of November 2011) provide an excellent example
      of how changing concepts on prokaryote taxonomy and the development of new
      methods have influenced the way in which the taxonomy of a single group of
      prokaryotes is treated. This review gives an overview of the taxonomy of the
      family Halobacteriaceae, showing the impact that methods of phenotypic
      characterization, numerical taxonomy, chemotaxonomy and especially polar lipid
      analysis, 16S rRNA gene sequence comparisons, multilocus type analysis and
      comparative genomics have had on their classification.

PMID- 22155758
TI  - Microbulbifer taiwanensis sp. nov., isolated from coastal soil.
AB  - A Gram-negative, non-spore-forming rod (CC-LN1-12(T)) was isolated from coastal
      soil samples of Lutao Island (Green Island), Taiwan, and its taxonomic position
      was studied. 16S rRNA gene sequence analysis showed that isolate CC-LN1-12(T) was
      grouped into the Microbulbifer cluster, with the highest similarities to
      Microbulbifer okinawensis ABABA23(T) (97.9 %), Microbulbifer maritimus TF-17(T)
      (97.7 %) and Microbulbifer donghaiensis CN85(T) (97.7 %), similarities to all
      other species of the genus Microbulbifer were lower than 96.8 %. The polyamine
      pattern contained the major compounds spermidine and cadaverine. The fatty acid
      profile, comprising the major fatty acids iso-C(15 : 0), iso-C(17 : 1)omega9c,
      C(18 : 1)omega7c and iso-C(11 : 0) 3-OH as the major hydroxylated fatty acid,
      supported the affiliation of strain CC-LN1-12(T) to the genus Microbulbifer. DNA
      DNA hybridizations between strain CC-LN1-12(T) and Microbulbifer okinawensis
      ABABA23(T), M. donghaiensis CN85(T) and M. maritimus JCM 12187(T) resulted in
      relatedness values of 21.5 % (14.3 %, reciprocal analysis), 35.9 % (48.5 %,
      reciprocal analysis) and 48.1 % (52.1 %, reciprocal analysis), respectively. From
      these data, as well as from physiological and biochemical tests, strain CC-LN1
      12(T) could be clearly differentiated from the most closely related species of
      the genus Microbulbifer. It is concluded that strain CC-LN1-12(T) represents a
      novel species, for which the name Microbulbifer taiwanensis sp. nov. is proposed.
      The type strain is CC-LN1-12(T) ( = LMG 26125(T) = CCM 7856(T)).

PMID- 22155759
TI  - Oceanitalea nanhaiensis gen. nov., sp. nov., an actinobacterium isolated from
      seawater.
AB  - A Gram-positive, motile, short-rod-shaped bacterium, designated strain
      JLT1488(T), was isolated from the South China Sea and investigated in a taxonomic
      study using a polyphasic approach. The peptidoglycan type determined for strain
      JLT1488(T) was A4alpha with lysine as the diagnostic cell-wall diamino acid and
      an interpeptide bridge of L-Lys-L-Glu. The polar lipids consisted of
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol,
      phosphatidylinositol mannosides, an unknown glycolipid and an unknown
      phospholipid. The only detected menaquinone was MK-8(H(4)), and the major fatty
      acids were summed feature 8 (C(18 : 1)omega7c/C(18 : 1)omega6c) , C(16 : 0) and
      summed feature 3 (C(16 : 1)omega7c/C(16 : 1)omega6c); significant amounts of C(12
      : 0) 3-OH, C(10 : 0) and C(19 : 0) cyclo omega8c were also present. The G+C
      content of the genomic DNA was 62.3 mol%. Comparison of the 16S rRNA gene
      sequence of strain JLT1488(T) with those of related type strains demonstrated
      that it represented a novel lineage within the family Bogoriellaceae, suborder
      Micrococcineae, being closely related to species of the genera Georgenia,
      Bogoriella and Cellulomonas (94.6-96.8 % sequence similarity). These results
      demonstrate that strain JLT1488(T) is a member of a new genus, for which the name
      Oceanitalea nanhaiensis gen. nov., sp. nov. is proposed. The type strain of the
      type species is JLT1488(T) ( = JCM 17755(T) = CGMCC 1.10826(T)).

PMID- 22155760
TI  - Reclassification of Bacillus beijingensis Qiu et al. 2009 and Bacillus ginsengi
      Qiu et al. 2009 as Bhargavaea beijingensis comb. nov. and Bhargavaea ginsengi
      comb. nov. and emended description of the genus Bhargavaea.
AB  - We have carried out a polyphasic taxonomic characterization of Bacillus
      beijingensis DSM 19037(T) and Bacillus ginsengi DSM 19038(T), which are closely
      related phylogenetically to Bhargavaea cecembensis LMG 24411(T). All three
      strains are Gram-stain-positive, non-motile, moderately halotolerant and non
      spore-forming. 16S rRNA gene sequence analyses showed that the strains
      constituted a coherent cluster, with sequence similarities between 99.7 and 98.7
      %. The percentage similarity on the basis of amino acid sequences deduced from
      partial gyrB gene nucleotide sequences of these three type strains was 96.1-92.7
      %. Phylogenetic trees based on the 16S rRNA gene and GyrB amino acid sequences,
      obtained by using three different algorithms, were consistent and showed that
      these three species constituted a deeply rooted cluster separated from the clades
      represented by the genera Bacillus, Planococcus, Planomicrobium, Sporosarcina,
      Lysinibacillus, Viridibacillus, Kurthia and Geobacillus, supporting their
      placement in the genus Bhargavaea. All three type strains have menaquinone MK-8
      as the major respiratory quinone and showed similar fatty acid profiles. The main
      polar lipids present in the three type strains were diphosphatidylglycerol and
      phosphatidylglycerol, and the three strains showed peptidoglycan type A4alpha
      with L-lysine as the diagnostic diamino acid. The DNA G+C contents of Bacillus
      beijingensis DSM 19037(T), Bacillus ginsengi DSM 19038(T) and Bhargavaea
      cecembensis LMG 24411(T) were 53.1, 50.2 and 53.7 mol%, respectively. The level
      of DNA-DNA hybridization among the three strains was 57-39 %, indicating that
      they are members of different species of the genus Bhargavaea. The phenotypic
      data are consistent with the placement of these three species in a single genus
      and support their differentiation at the species level. On the basis of these
      data, we have emended the description of the genus Bhargavaea and propose the
      reclassification of Bacillus beijingensis and Bacillus ginsengi to the genus
      Bhargavaea, as Bhargavaea beijingensis comb. nov. (type strain ge10(T)  = DSM
      19037(T)  = CGMCC 1.6762(T)) and Bhargavaea ginsengi comb. nov. (type strain
      ge14(T)  = DSM 19038(T)  = CGMCC 1.6763(T)).

PMID- 22155761
TI  - Multilocus sequence analysis of Bosea species and description of Bosea lupini sp.
      nov., Bosea lathyri sp. nov. and Bosea robiniae sp. nov., isolated from legumes.
AB  - Gram-negative, rod-shaped bacteria were isolated from root nodules of Lupinus
      polyphyllus, Lathyrus latifolius and Robinia pseudoacacia. Based on the 16S rRNA
      gene phylogeny, they were closely related to Bosea species (100-97 % similarity),
      belonging to the class Alphaproteobacteria, family Bradyrhizobiaceae. The closest
      relatives of LMG 26383(T), LMG 26379(T) and LMG 26381(T) were respectively the
      type strains of Bosea thiooxidans (99.6 %), B. eneae (98.3 %) and B.
      minatitlanensis (99.0 %). Chemotaxonomic data, including major fatty acid
      profiles, supported the assignment of our strains to the genus Bosea. Analysis of
      the concatenated sequences of five housekeeping genes (atpD, dnaK, gyrB, recA and
      rpoB) and the results of DNA-DNA hybridizations and physiological and biochemical
      tests allowed genotypic and phenotypic differentiation of our strains from each
      other and from the five Bosea species with validly published names. No nodA or
      nodC genes could be amplified, while nifH PCR gave non-specific products. On the
      basis of genotypic and phenotypic data, three novel species, Bosea lupini sp.
      nov. (type strain LMG 26383(T)  = CCUG 61248(T)  = R-45681(T)), Bosea lathyri sp.
      nov. (type strain LMG 26379(T)  = CCUG 61247(T)  = R-46060(T)) and Bosea robiniae
      sp. nov. (type strain LMG 26381(T)  = CCUG 61249(T)  = R-46070(T)), are proposed.

PMID- 22155762
TI  - Aquamicrobium ahrensii sp. nov. and Aquamicrobium segne sp. nov., isolated from
      experimental biofilters.
AB  - Two groups of Gram-negative, aerobic bacterial strains previously isolated from
      experimental biofilters were investigated to determine their taxonomic position.
      Based on their 16S rRNA gene sequences, these isolates formed two distinct groups
      within the genus Aquamicrobium. The gene sequence similarities of the new
      isolates to the type strains of Aquamicrobium species were below 98.3 %. The
      presence of ubiquinone-10, C(18 : 1) cis 11 as the predominant fatty acid and a
      polar lipid pattern with phosphatidylglycerol, phosphatidylcholine,
      diphosphatidylglycerol and phosphatidylethanolamine was in accordance with the
      characteristics of this genus. The results of DNA-DNA hybridization, biochemical
      tests and chemotaxonomic properties allowed genotypic and phenotypic
      differentiation of the strains from all recognized species of the genus
      Aquamicrobium. Therefore, the isolates were assigned to two novel species of this
      genus for which the names Aquamicrobium ahrensii sp. nov. (type strain 905/1(T) =
      DSM 19730(T) = CCUG 55251(T)) and Aquamicrobium segne sp. nov. (type strain
      1006/1(T) = DSM 19714(T) = CCUG 55250(T)) are proposed. An emended description of
      the genus Aquamicrobium is also presented.

PMID- 22155763
TI  - Suitability of differently formulated dry powder Newcastle disease vaccines for
      mass vaccination of poultry.
AB  - Dry powders containing a live-attenuated Newcastle disease vaccine (LZ58 strain)
      and intended for mass vaccination of poultry were prepared by spray drying using
      mannitol in combination with trehalose or inositol, polyvinylpyrrolidone (PVP)
      and/or bovine serum albumin (BSA) as stabilizers. These powders were evaluated
      for vaccine stabilizing capacity during production and storage (at 6  degrees C
      and 25  degrees C), moisture content, hygroscopicity and dry powder
      dispersibility. A mixture design, varying the ratio of mannitol, inositol and
      BSA, was used to select the stabilizer combination which resulted in the desired
      powder properties (i.e. good vaccine stability during production and storage, low
      moisture content and hygroscopicity and good dry dispersibility). Inositol
      containing powders had the same vaccine stabilizing capacity as trehalose
      powders, but were less hygroscopic. Incorporation of BSA enhanced the vaccine
      stability in the powders compared to PVP-containing formulations. However,
      increasing the BSA concentration increased the hygroscopicity and reduced the dry
      dispersibility of the powder. No valid mathematical model could be calculated for
      vaccine stability during production or storage, but the individual experiments
      indicated that a formulation combining mannitol, inositol and BSA in a ratio of
      73.3:13.3:13.3 (wt/wt) resulted in the lowest vaccine titre loss during
      production (1.6-2.0 log(10) 50% egg infectious dose (EID(50)) and storage at 6 
      degrees C (max. 0.8 log(10) EID(50) after 6 months) in combination with a low
      moisture content (1.1-1.4%), low hygroscopicity (1.9-2.1% water uptake at 60%
      relative humidity) and good dry dispersibility properties.

PMID- 22155764
TI  - Assessment of enzymatic prodrug stability in human, dog and simulated intestinal
      fluids.
AB  - The aim of this study was to determine the stability of three ester prodrugs,
      chloramphenicol succinate, enalapril and candesartan cilexetil, in human proximal
      small intestinal fluid (HIF), dog proximal small intestinal fluids (DIF) and
      simulated intestinal fluid (FaSSIF), with the addition of pancreatin. The total
      protein content in the proximal jejunal fluids was determined in HIF and DIF,
      respectively. Candesartan cilexetil was significantly degraded in HIF (initial
      t(1/2(0-5 min))=5.4 +/- 0.5 min) and in DIF (initial t(1/2(0-5 min))=5.7 +/- 0.1
      min), while chloramphenicol succinate and enalapril were stable in both media.
      The degradation of candesartan cilexetil was shown to be mediated by enzymes
      following Michaelis-Menten enzyme kinetics and was inhibited by addition of
      esterase inhibitors. The enzymatic capacity reflected by V(max) was 4-fold higher
      in DIF than in HIF and correlated to its 2-fold higher protein concentration. The
      degradation of candesartan cilexetil in the FaSSIF-pancreatin solution was slower
      (t(1/2)=207 +/- 34 min) than the degradation in both HIF and DIF. Changing the pH
      to the enzyme optima or increasing the amount of pancreatin, increased the
      degradation rate of candesartan cilexetil, but not in the magnitude as in HIF. As
      a result, two in vitro models, based on in vivo intestinal fluids, were developed
      using candesartan cilexetil as a model drug. The DIF seems to be a reasonably
      good model for HIF, although the degradation capacity seems to be somewhat
      higher, possibly due to the higher enzyme concentration in DIF. Future
      investigations will develop novel enzymatic based in vitro models for rapid
      assessment and biopharmaceutical screening tools for prodrugs.

PMID- 22155765
TI  - Development of a fluorescent microsphere immunoassay for detection of antibodies
      against porcine reproductive and respiratory syndrome virus using oral fluid
      samples as an alternative to serum-based assays.
AB  - For effective disease surveillance, rapid and sensitive assays are needed to
      detect antibodies developed in response to porcine reproductive and respiratory
      syndrome virus (PRRSV) infection. In this study, we developed a multiplexed
      fluorescent microsphere immunoassay (FMIA) for detection of PRRSV-specific
      antibodies in oral fluid and serum samples. Recombinant nucleocapsid protein (N)
      and nonstructural protein 7 (nsp7) from both PRRSV genotypes (type I and type II)
      were used as antigens and covalently coupled to Luminex fluorescent microspheres.
      Based on an evaluation of 488 oral fluid samples with known serostatus, the oral
      fluid-based FMIAs achieved >92% sensitivity and 91% specificity. For serum
      samples (n = 1,639), the FMIAs reached >98% sensitivity and 95% specificity. The
      assay was further employed to investigate the kinetics of the antibody response
      in infected pigs. In oral fluid, the N protein was more sensitive for the
      detection of early infection (7 and 14 days postinfection), but nsp7 detected a
      higher level and longer duration of antibody response (28 days postinfection). In
      serum, the antibodies specific to nsp7 and N proteins were detected as early as 7
      days postinfection, and the responses lasted more than 202 days. This study
      provides a framework from which a more robust assay could be developed to profile
      the immune response to multiple PRRSV antigens in a single test. The development
      of oral fluid-based diagnostic tests will change the way we survey diseases in
      swine herds and improve our ability to cheaply and efficiently track PRRSV
      infections in both populations and individual animals.

PMID- 22155766
TI  - Characterization of an immunodominant antigenic epitope from Trypanosoma cruzi as
      a biomarker of chronic Chagas' disease pathology.
AB  - Nowadays, the techniques available for chronic Chagas' disease diagnosis are very
      sensitive; however, they do not allow discrimination of the patient's clinical
      stages of the disease. The present paper describes that three out of the five
      different repeats contained in the Trypanosoma cruzi TcCA-2 membrane protein
      (3972-FGQAAAGDKPPP, 6303-FGQAAAGDKPAP, and 3973-FGQAAAGDKPSL) are recognized with
      high sensitivity (>90%) by sera from chronic Chagas' disease patients and that
      they are not recognized by sera from patients in the acute phase of the disease.
      A total of 133 serum samples from chagasic patients and 50 serum samples from
      healthy donors were tested. In addition, sera from 15 patients with different
      autoimmune diseases, 43 serum samples from patients suffering an infectious
      disease other than Chagas' disease, and 38 serum samples from patients with
      nonchagasic cardiac disorders were also included in this study. The residue 3973
      peptide shows a specificity of >98%, as it is not recognized by individuals with
      autoimmune and inflammatory processes or by patients with a nonchagasic
      cardiomyopathy. Remarkably, the levels of antibody against the 3973 epitope
      detected by the sera from Chagas' disease patients in the symptomatic chronic
      phase, involving cardiac or digestive alterations, are higher than those detected
      by the sera from Chagas' disease patients in the indeterminate phase of the
      disease. It is suggested that the diagnostic technique described could also be
      used to indicate the degree of pathology. The amino acids F, Q, and DKP located
      in the peptide at positions 1, 3, and 8 to 10, respectively, are essential to
      conform to the immunodominant antigenic epitope.

PMID- 22155767
TI  - Identification of immunogenic and virulence-associated Campylobacter jejuni
      proteins.
AB  - With the aim of identifying proteins important for host interaction and
      virulence, we have screened an expression library of NCTC 11168 Campylobacter
      jejuni genes for highly immunogenic proteins. A commercial C. jejuni open reading
      frame (ORF) library consisting of more than 1,600 genes was transformed into the
      Escherichia coli expression strain BL21(DE3), resulting in 2,304 clones. This
      library was subsequently screened for immunogenic proteins using antibodies
      raised in rabbit against a clinical isolate of C. jejuni; this resulted in 52
      highly reactive clones representing 25 different genes after sequencing. Selected
      candidate genes were inactivated in C. jejuni NCTC 11168, and the virulence was
      examined using INT 407 epithelial cell line and motility, biofilm,
      autoagglutination, and serum resistance assays. These investigations revealed C.
      jejuni antigen 0034c (Cj0034c) to be a novel virulence factor and support the
      usefulness of the method. Further, several antigens were tested as vaccine
      candidates in two mouse models, in which Cj0034c, Cj0404, and Cj0525c resulted in
      a reduction of invasion in spleen and liver after challenge.

PMID- 22155768
TI  - Immunogenicity of the quadrivalent human papillomavirus (type 6/11/16/18) vaccine
      in males 16 to 26 years old.
AB  - Human papillomavirus (HPV) infection can lead to significant disease in males,
      including anogenital warts, intraepithelial neoplasias, and several types of oral
      and anogenital cancers. The quadrivalent HPV (type 6/11/16/18) L1 virus-like
      particle (VLP) vaccine (qHPV vaccine; Gardasil) has recently been demonstrated to
      prevent persistent infection and associated disease related to vaccine HPV types
      in males. We report the overall immunogenicity results from a trial of the
      quadrivalent HPV vaccine in males. Overall, 3,463 heterosexual men and 602 men
      who had sex with men were enrolled into a randomized, placebo-controlled, double
      blind safety, immunogenicity, and efficacy study. Serum samples were collected
      prior to vaccination at day 1 and at months 7, 24, and 36 postvaccination.
      Immunogenicity was evaluated with a multiplex, competitive Luminex immunoassay.
      Almost all subjects (97.4 to 99.2%) seroconverted for vaccine HPV types by month
      7. At month 36, 88.9%, 94.0%, 97.9%, and 57.0% of subjects were still
      seropositive for HPV-6, -11, -16, and -18, respectively. For all vaccine HPV
      types, black subjects had significantly higher antibody titers at month 7 than
      did both Caucasian and Asian subjects. An anamnestic antibody response was seen
      in men seropositive before vaccination. The vaccine was highly immunogenic in
      males 16 to 23 years of age; responses were comparable to those observed in
      women. Furthermore, the immune responses were consistent with the established
      efficacy of the vaccine in the prevention of incident and persistent HPV
      infection, anogenital warts, and anal intraepithelial neoplasia.

PMID- 22155769
TI  - Use of pre-S protein-containing hepatitis B virus surface antigens and a powerful
      adjuvant to develop an immune therapy for chronic hepatitis B virus infection.
AB  - A hepatitis B virus (HBV) vaccine has been developed using a new adjuvant and HBV
      surface antigens produced from a CHO cell line. The purified HBV surface antigens
      are composed of L protein, M protein, and S protein in a mixture of 20- and 40-nm
      diameter particles and filamentous forms. This HBV surface antigen, formulated
      with L-pampo, a proprietary adjuvant, induced 10 times more antibody than the
      same antigen with alum and was capable of inducing strong immune responses in
      three different HBV transgenic mice. In spite of the presence of a large amount
      of HBV antigen in the blood, no antibody against HBV surface antigen was normally
      detected in these transgenic mice. After immunization, the HBV antigen was also
      cleared from the blood.

PMID- 22155770
TI  - Effect of electrocardiographic lead placement on localization of outflow tract
      tachycardias.
AB  - BACKGROUND: The origin of outflow tract ventricular tachycardia (OTVT) can be
      predicted from a surface electrocardiogram: indexes of R-wave amplitudes in leads
      V(1) and V(2) are used to differentiate a right origin from a left origin, while
      the axis of lead I differentiates an anterior origin from a posterior origin.
      Incorrect electrode placement is clinically common and may alter predictability
      of OTVTs. OBJECTIVE: To explore the influence of vertical deviation in leads V(1)
      and V(2) and arm lead position on the QRS morphology of OTVTs. METHODS: Vertical
      deviation of leads V(1) and V(2) was studied in 18 patients with OTVTs.
      Ventricular premature depolarization beats were recorded in the standard
      position, superior position, and inferior position. The effect of arm lead
      position was studied in a separate cohort of 16 patients: ventricular premature
      depolarizations were recorded with limb leads positioned over the shoulders and
      over the chest. The origin of tachycardia was determined by using activation
      mapping and confirmed by successful ablation. RESULTS: Superior displacement of
      leads V(1) and V(2) reduced the R-wave amplitude and led to a decreased R/S ratio
      (0.11 +/- 0.09 vs 0.17 +/- 0.1; P <.01), while inferior displacement of leads
      V(1) and V(2) resulted in an increased R-wave amplitude and led to an increased
      R/S ratio (0.46 +/- 0.35 vs 0.17 +/- 0.1; P <.01). Anterior displacement of the
      arm leads from shoulders to chest resulted in the reduction in the R-wave
      amplitude in lead I (0.25 +/- 0.30 mV vs 0.04 +/- 0.43 mV; P <.05). CONCLUSIONS:
      Small changes in electrocardiographic electrode placement markedly alter the QRS
      morphology of OTVTs and thus alter the predictability of OTVT origin. These
      deviations are well within the range of clinical application and have the
      potential to misdirect ablation procedures.

PMID- 22155771
TI  - Surface-localized spermidine protects the Pseudomonas aeruginosa outer membrane
      from antibiotic treatment and oxidative stress.
AB  - Extracellular DNA acts as a cation chelator and induces the expression of
      antibiotic resistance genes regulated by Mg(2+) levels. Here we report the
      characterization of novel DNA-induced genes in Pseudomonas aeruginosa that are
      annotated as homologs of the spermidine synthesis genes speD (PA4773) and speE
      (PA4774). The addition of sublethal concentrations of DNA and membrane-damaging
      antibiotics induced expression of the genes PA4773 to PA4775, as shown using
      transcriptional lux fusions and quantitative RT-PCR. Exogenous polyamine addition
      prevented DNA- and peptide-mediated gene induction. Mutation of PA4774 resulted
      in an increased outer membrane (OM) susceptibility phenotype upon polymyxin B,
      CP10A, and gentamicin treatment. When the membrane-localized fluorescent probe
      C(11)-BODIPY(581/591) was used as an indicator of peroxidation of membrane
      lipids, the PA4774::lux mutant demonstrated an increased susceptibility to
      oxidative membrane damage from H(2)O(2) treatment. Addition of exogenous
      polyamines protected the membranes of the PA4774::lux mutant from polymyxin B and
      H(2)O(2) treatment. Polyamines from the outer surface were isolated and shown to
      contain putrescine and spermidine by using high-performance liquid chromatography
      and mass spectrometry. The PA4774::lux mutant did not produce spermidine on the
      cell surface, but genetic complementation restored surface spermidine production
      as well as the antibiotic and oxidative stress resistance phenotypes of the
      membrane. We have identified new functions for spermidine on the cell surface and
      propose that polyamines are produced under Mg(2+)-limiting conditions as an
      organic polycation to bind lipopolysaccharide (LPS) and to stabilize and protect
      the outer membrane against antibiotic and oxidative damage.

PMID- 22155772
TI  - Isolation and characterization of the Prochlorococcus carboxysome reveal the
      presence of the novel shell protein CsoS1D.
AB  - Cyanobacteria, including members of the genus Prochlorococcus, contain
      icosahedral protein microcompartments known as carboxysomes that encapsulate
      multiple copies of the CO(2)-fixing enzyme ribulose 1,5-bisphosphate
      carboxylase/oxygenase (RubisCO) in a thin protein shell that enhances the
      catalytic performance of the enzyme in part through the action of a shell
      associated carbonic anhydrase. However, the exact mechanism by which
      compartmentation provides a catalytic advantage to the enzyme is not known.
      Complicating the study of cyanobacterial carboxysomes has been the inability to
      obtain homogeneous carboxysome preparations. This study describes the first
      successful purification and characterization of carboxysomes from the marine
      cyanobacterium Prochlorococcus marinus MED4. Because the isolated P. marinus MED4
      carboxysomes were free from contaminating membrane proteins, their protein
      complement could be assessed. In addition to the expected shell proteins, the
      CsoS1D protein that is not encoded by the canonical cso gene clusters of alpha
      cyanobacteria was found to be a low-abundance shell component. This finding and
      supporting comparative genomic evidence have important implications for
      carboxysome composition, structure, and function. Our study indicates that
      carboxysome composition is probably more complex than was previously assumed
      based on the gene complements of the classical cso gene clusters.

PMID- 22155773
TI  - A single-domain FlgJ contributes to flagellar hook and filament formation in the
      Lyme disease spirochete Borrelia burgdorferi.
AB  - FlgJ plays a very important role in flagellar assembly. In the enteric bacteria,
      flgJ null mutants fail to produce the flagellar rods, hooks, and filaments but
      still assemble the integral membrane-supramembrane (MS) rings. These mutants are
      nonmotile. The FlgJ proteins consist of two functional domains. The N-terminal
      rod-capping domain acts as a scaffold for rod assembly, and the C-terminal domain
      acts as a peptidoglycan (PG) hydrolase (PGase), which allows the elongating
      flagellar rod to penetrate through the PG layer. However, the FlgJ homologs in
      several bacterial phyla (including spirochetes) often lack the PGase domain. The
      function of these single-domain FlgJ proteins remains elusive. Herein, a single
      domain FlgJ homolog (FlgJ(Bb)) was studied in the Lyme disease spirochete
      Borrelia burgdorferi. Cryo-electron tomography analysis revealed that the
      flgJ(Bb) mutant still assembled intact flagellar basal bodies but had fewer and
      disoriented flagellar hooks and filaments. Consistently, Western blots showed
      that the levels of flagellar hook (FlgE) and filament (FlaB) proteins were
      substantially decreased in the flgJ(Bb) mutant. Further studies disclosed that
      the decreases of FlgE and FlaB in the mutant occurred at the posttranscriptional
      level. Microscopic observation and swarm plate assay showed that the motility of
      the flgJ(Bb) mutant was partially deficient. The altered phenotypes were
      completely restored when the mutant was complemented. Collectively, these results
      indicate that FlgJ(Bb) is involved in the assembly of the flagellar hook and
      filament but not the flagellar rod in B. burgdorferi. The observed phenotype is
      different from that of flgJ mutants in the enteric bacteria.

PMID- 22155774
TI  - EspD is critical for the virulence-mediating ESX-1 secretion system in
      Mycobacterium tuberculosis.
AB  - ESAT-6 system 1 (ESX-1)-mediated secretion in Mycobacterium tuberculosis is
      dependent on proteins encoded by the cotranscribed espA-espC-espD gene cluster.
      While the roles of EspA and EspC with respect to the ESX-1 secretion system have
      been actively investigated, the function of EspD remains unknown. We show that
      EspD is secreted by M. tuberculosis, but unlike EspA and EsxA, its export does
      not exclusively require the ESX-1 system. Evidence for stabilization of cellular
      levels of EspA and EspC by EspD is presented, and depletion of EspD results in
      loss of EsxA secretion. Site-directed mutagenesis of EspD reveals that its role
      in the maintenance of cellular levels of EspA in M. tuberculosis is distinct from
      its facilitation of EsxA secretion. The same mutagenesis experiments have also
      shown that secretion of EspD is not required for the secretion of EsxA. Our
      findings highlight a critical and complex role for EspD in modulating the ESX-1
      secretion system in M. tuberculosis.

PMID- 22155775
TI  - Genes involved in immunity to and secretion of aureocin A53, an atypical class II
      bacteriocin produced by Staphylococcus aureus A53.
AB  - Aureocin A53 is an antimicrobial peptide produced by Staphylococcus aureus A53.
      The genetic determinants involved in aureocin A53 production and immunity to its
      action are organized in at least four transcriptional units encoded by the 10.4
      kb plasmid pRJ9. One transcriptional unit carries only the bacteriocin structural
      gene, aucA. No immunity gene is found downstream of aucA, as part of the same
      transcriptional unit. Further downstream of aucA is found an operon which
      contains the three genes aucEFG, whose products seem to associate to form a
      dedicated ABC transporter. When aucEFG were expressed in RN4220, an aureocin A53
      sensitive S. aureus strain, this strain became partially resistant to the
      bacteriocin. A gene disruption mutant in aucE was defective in aureocin A53
      externalization and more sensitive to aureocin A53 than the wild-type strain,
      showing that aucEFG are involved in immunity to aureocin A53 by active extrusion
      of the bacteriocin. Full resistance to aureocin A53 was exhibited by
      transformants carrying, besides aucEFG, the operon formed by two genes, aucIB and
      aucIA, located between aucA and aucEFG and carried in the opposite strand. AucIA
      and AucIB share similarities with hypothetical proteins not found in the gene
      clusters of other bacteriocins. A gene disruption mutant in orf8, located
      upstream of aucA and whose product exhibits about 50% similarity to a number of
      hypothetical membrane proteins found in many Gram-positive bacteria, was strongly
      affected in aureocin A53 externalization but resistant to aureocin A53,
      suggesting that Orf8 is also involved in aureocin A53 secretion.

PMID- 22155776
TI  - The translocation domain in trimeric autotransporter adhesins is necessary and
      sufficient for trimerization and autotransportation.
AB  - Trimeric autotransporter adhesins (TAAs) comprise one of the secretion pathways
      of the type V secretion system. The mechanism of their translocation across the
      outer membrane remains unclear, but it most probably occurs by the formation of a
      hairpin inside the beta-barrel translocation unit, leading to transportation of
      the passenger domain from the C terminus to the N terminus through the lumen of
      the beta-barrel. We further investigated the phenomenon of autotransportation and
      the rules that govern it. We showed by coexpressing different Escherichia coli
      immunoglobulin-binding (Eib) proteins that highly similar TAAs could form
      stochastically mixed structures (heterotrimers). We further investigated this
      phenomenon by coexpressing two more distantly related TAAs, EibA and YadA. These,
      however, did not form heterotrimers; indeed, coexpression was lethal to the
      cells, leading to elimination of one or another of the genes. However,
      substituting in either protein the barrel of the other one so that the barrels
      were identical led to formation of heterotrimers as for Eibs. Our work shows that
      trimerization of the beta-barrel, but not the passenger domain, is necessary and
      sufficient for TAA secretion while the passenger domain is not.

PMID- 22155778
TI  - Mutation of the sensor kinase chvG in Rhizobium leguminosarum negatively impacts
      cellular metabolism, outer membrane stability, and symbiosis.
AB  - Two-component signal transduction systems (TCS) are a main strategy used by
      bacteria to sense and adapt to changes in their environment. In the legume
      symbiont Rhizobium leguminosarum biovar viciae VF39, mutation of chvG, a
      histidine kinase, caused a number of pleiotropic phenotypes. ChvG mutants are
      unable to grow on proline, glutamate, histidine, or arginine as the sole carbon
      source. The chvG mutant secreted smaller amounts of acidic and neutral surface
      polysaccharides and accumulated abnormally large amounts of poly-beta
      hydroxybutyrate. Mutation of chvG caused symbiotic defects on peas, lentils, and
      vetch; nodules formed by the chvG mutant were small and white and contained only
      a few cells that had failed to differentiate into bacteroids. Mutation of chvG
      also destabilized the outer membrane of R. leguminosarum, resulting in increased
      sensitivity to membrane stressors. Constitutive expression of ropB, the outer
      membrane protein-encoding gene, restored membrane stability and rescued the
      sensitivity phenotypes described above. Similar phenotypes have been described
      for mutations in other ChvG-regulated genes encoding a conserved operon of
      unknown function and in the fabXL genes required for synthesis of the lipid A
      very-long-chain fatty acid, suggesting that ChvG is a key component of the
      envelope stress response in Rhizobium leguminosarum. Collectively, the results of
      this study demonstrate the important and unique role the ChvG/ChvI TCS plays in
      the physiology, metabolism, and symbiotic competency of R. leguminosarum.

PMID- 22155777
TI  - BpaB and EbfC DNA-binding proteins regulate production of the Lyme disease
      spirochete's infection-associated Erp surface proteins.
AB  - Vector-borne pathogens regulate their protein expression profiles, producing
      factors during host infection that differ from those produced during vector
      colonization. The Lyme disease agent, Borrelia burgdorferi, produces Erp surface
      proteins throughout mammalian infection and represses their synthesis during
      colonization of vector ticks. Known functions of Erp proteins include binding of
      host laminin, plasmin(ogen), and regulators of complement activation. A DNA
      region immediately 5' of erp operons, the erp operator, is required for
      transcriptional regulation. The B. burgdorferi BpaB and EbfC proteins exhibit
      high in vitro affinities for erp operator DNA. In the present studies, chromatin
      immunoprecipitation (ChIP) demonstrated that both proteins bind erp operator DNA
      in vivo. Additionally, a combination of in vivo and in vitro methods demonstrated
      that BpaB functions as a repressor of erp transcription, while EbfC functions as
      an antirepressor.

PMID- 22155779
TI  - The iron-binding protein Dps2 confers peroxide stress resistance on Bacillus
      anthracis.
AB  - Iron is an essential nutrient that is implicated in most cellular oxidation
      reactions. However, iron is a highly reactive element that, if not appropriately
      chaperoned, can react with endogenously and exogenously generated oxidants such
      as hydrogen peroxide to generate highly toxic hydroxyl radicals. Dps proteins
      (DNA-binding proteins from starved cells) form a distinct class (the
      miniferritins) of iron-binding proteins within the ferritin superfamily. Bacillus
      anthracis encodes two Dps-like proteins, Dps1 and Dps2, the latter being one of
      the main iron-containing proteins in the cytoplasm. In this study, the function
      of Dps2 was characterized in vivo. A B. anthracis Deltadps2 mutant was
      constructed by double-crossover mutagenesis. The growth of the Deltadps2 mutant
      was unaffected by excess iron or iron-limiting conditions, indicating that the
      primary role of Dps2 is not that of iron sequestration and storage. However, the
      Deltadps2 mutant was highly sensitive to H(2)O(2), and pretreatment of the cells
      with the iron chelator deferoxamine mesylate (DFM) significantly reduced its
      sensitivity to H(2)O(2) stress. In addition, the transcription of dps2 was
      upregulated by H(2)O(2) treatment and derepressed in a perR mutant, indicating
      that dps2 is a member of the regulon controlled by the PerR regulator. This
      indicates that the main role of Dps2 is to protect cells from peroxide stress by
      inhibiting the iron-catalyzed production of OH.

PMID- 22155780
TI  - Involvement of T6 pili in biofilm formation by serotype M6 Streptococcus
      pyogenes.
AB  - The group A streptococcus (GAS) Streptococcus pyogenes is known to cause self
      limiting purulent infections in humans. The role of GAS pili in host cell
      adhesion and biofilm formation is likely fundamental in early colonization. Pilus
      genes are found in the FCT (fibronectin-binding protein, collagen-binding
      protein, and trypsin-resistant antigen) genomic region, which has been classified
      into nine subtypes based on the diversity of gene content and nucleotide
      sequence. Several epidemiological studies have indicated that FCT type 1 strains,
      including serotype M6, produce large amounts of monospecies biofilm in vitro. We
      examined the direct involvement of pili in biofilm formation by serotype M6
      clinical isolates. In the majority of tested strains, deletion of the tee6 gene
      encoding pilus shaft protein T6 compromised the ability to form biofilm on an
      abiotic surface. Deletion of the fctX and srtB genes, which encode pilus
      ancillary protein and class C pilus-associated sortase, respectively, also
      decreased biofilm formation by a representative strain. Unexpectedly, these
      mutant strains showed increased bacterial aggregation compared with that of the
      wild-type strain. When the entire FCT type 1 pilus region was ectopically
      expressed in serotype M1 strain SF370, biofilm formation was promoted and
      autoaggregation was inhibited. These findings indicate that assembled FCT type 1
      pili contribute to biofilm formation and also function as attenuators of
      bacterial aggregation. Taken together, our results show the potential role of FCT
      type 1 pili in the pathogenesis of GAS infections.

PMID- 22155781
TI  - Anti TNF-alpha in refractory Takayasu's arteritis: cases series and review of the
      literature.
AB  - Takayasu arteritis (TA) is a rare large vessels vasculitis. Conventional therapy
      consists of glucocorticoids which may be associated with other immunosuppressive
      drugs. However, some patients fail to achieve remission with conventional
      treatment. The use of anti-tumor necrosis factor-alpha (TNF-alpha) in patients
      with difficult to treat TA could be useful. We report here the main
      characteristics, treatment and outcome of 84 patients (5 personal cases and 79
      patients from the literature) with refractory Takayasu arteritis treated with
      anti TNF-alpha. The mean age was 28.5years [median 26.0years, range 7-61years],
      with 74/83 (89%) of female. All patients, except one, were inadequately
      controlled with other immunosuppressive regimens before anti TNF-alpha therapy.
      First line of anti-TNF-alpha included infliximab (IFX) in 81% (68/84) and
      etanercept (ETA) in 19% (16/84). Most patients received IFX at 5mg/kg associated
      to methotrexate or azathioprine. Thirty one out of 84 (37%) patients achieved a
      complete remission, and 45 (53.5%) were partial responders. There were 8 (9.5%)
      non responders at all. Twenty seven out of 84 (32%) patients needed to increase
      the dose of anti TNF-alpha because of uncontrolled disease and 15 (18%) needed to
      change of anti TNF-alpha. Glucocorticoids have been tapered in 41/79 (52%) [from
      20mg (13.1-60) to 2.5mg (0-10) daily, at baseline and after anti-TNF,
      respectively, p<0.0001] and discontinued in 31/77 (40%). After a median follow-up
      of 10months [range 3-82], 17 (20%) side effects were recorded leading to
      discontinuation of anti TNF-alpha in 8 cases. They included mainly infections,
      and hypersensitivity reactions. In conclusion, anti-TNF-alpha are an efficient
      therapy in refractory TA patients although side effects are observed in 20% of
      cases. Further studies are warranted to assess the long term efficacy and safety
      of anti-TNF in TA and to better define if they should be prescribed earlier in
      the course of TA.

PMID- 22155782
TI  - Transient receptor potential vanilloid-1 (TRPV1) is a mediator of lung toxicity
      for coal fly ash particulate material.
AB  - Environmental particulate matter (PM) pollutants adversely affect human health,
      but the molecular basis is poorly understood. The ion channel transient receptor
      potential vanilloid-1 (TRPV1) has been implicated as a sensor for environmental
      PM and a mediator of adverse events in the respiratory tract. The objectives of
      this study were to determine whether TRPV1 can distinguish chemically and
      physically unique PM that represents important sources of air pollution; to
      elucidate the molecular basis of TRPV1 activation by PM; and to ascertain the
      contributions of TRPV1 to human lung cell and mouse lung tissue responses exposed
      to an insoluble PM agonist, coal fly ash (CFA1). The major findings of this study
      are that TRPV1 is activated by some, but not all of the prototype PM materials
      evaluated, with rank-ordered responses of CFA1 > diesel exhaust PM > crystalline
      silica; TRP melastatin-8 is also robustly activated by CFA1, whereas other TRP
      channels expressed by airway sensory neurons and lung epithelial cells that may
      also be activated by CFA1, including TRPs ankyrin 1 (A1), canonical 4alpha
      (C4alpha), M2, V2, V3, and V4, were either slightly (TRPA1) or not activated by
      CFA1; activation of TRPV1 by CFA1 occurs via cell surface interactions between
      the solid components of CFA1 and specific amino acid residues of TRPV1 that are
      localized in the putative pore-loop region; and activation of TRPV1 by CFA1 is
      not exclusive in mouse lungs but represents a pathway by which CFA1 affects the
      expression of selected genes in lung epithelial cells and airway tissue.

PMID- 22155783
TI  - Protein kinase C regulation of 12-lipoxygenase-mediated human platelet
      activation.
AB  - Platelet activation is important in the regulation of hemostasis and thrombosis.
      Uncontrolled activation of platelets may lead to arterial thrombosis, which is a
      major cause of myocardial infarction and stroke. After activation, metabolism of
      arachidonic acid (AA) by 12-lipoxygenase (12-LOX) may play a significant role in
      regulating the degree and stability of platelet activation because inhibition of
      12-LOX significantly attenuates platelet aggregation in response to various
      agonists. Protein kinase C (PKC) activation is also known to be an important
      regulator of platelet activity. Using a newly developed selective inhibitor for
      12-LOX and a pan-PKC inhibitor, we investigated the role of PKC in 12-LOX
      mediated regulation of agonist signaling in the platelet. To determine the role
      of PKC within the 12-LOX pathway, a number of biochemical endpoints were
      measured, including platelet aggregation, calcium mobilization, and integrin
      activation. Inhibition of 12-LOX or PKC resulted in inhibition of dense granule
      secretion and attenuation of both aggregation and alphaIIbbeta(3) activation.
      However, activation of PKC downstream of 12-LOX inhibition rescued agonist
      induced aggregation and integrin activation. Furthermore, inhibition of 12-LOX
      had no effect on PKC-mediated aggregation, indicating that 12-LOX is upstream of
      PKC. These studies support an essential role for PKC downstream of 12-LOX
      activation in human platelets and suggest 12-LOX as a possible target for
      antiplatelet therapy.

PMID- 22155784
TI  - Factors in client-clinician interaction that influence hearing aid adoption.
AB  - The influence of client-clinician interactions has not been emphasized in hearing
      health care, despite the extensive evidence of the impact of the provider-patient
      interaction on health outcomes. The purpose of this study was to identify factors
      in the client-clinician interaction that may influence hearing aid adoption.
      Thirteen adults who had received a hearing aid recommendation within the previous
      3 months and 10 audiologists participated in a study to generate, sort, and rate
      the importance of factors in client-clinician interaction that may influence the
      hearing aid purchase decision. A concept mapping approach was used to define
      meaningful clusters of factors. Quantitative analysis and qualitative
      interpretation of the statements resulted in eight concepts. The concepts in
      order of their importance are (a) Ensuring client comfort, (b) Understanding and
      meeting client needs, (c) Client-centered traits and actions, (d) Acknowledging
      client as an individual, (e) Imposing undue pressure and discomfort, (f)
      Conveying device information by clinician, (g) Supporting choices and shared
      decision making, and (h) Factors in client readiness. Two overarching themes of
      client-centered interaction and client empowerment were identified. Results
      highlight the influence of the client-clinician interaction in hearing aid
      adoption and suggest the possibility of improving hearing aid adoption by
      empowering clients through a client-centered interaction.

PMID- 22155786
TI  - Neuronal growth cone retraction relies on proneurotrophin receptor signaling
      through Rac.
AB  - Growth of axons and dendrites is a dynamic process that involves guidance
      molecules, adhesion proteins, and neurotrophic factors. Although neurite
      extension is stimulated by the neurotrophin nerve growth factor (NGF), we found
      that the precursor of NGF, proNGF, induced acute collapse of growth cones of
      cultured hippocampal neurons. This retraction was initiated by an interaction
      between the p75 neurotrophin receptor (p75NTR) and the sortilin family member
      SorCS2 (sortilin-related VPS10 domain-containing receptor 2). Binding of proNGF
      to the p75NTR-SorCS2 complex induced growth cone retraction by initiating the
      dissociation of the guanine nucleotide exchange factor Trio from the p75NTR
      SorCS2 complex, resulting in decreased Rac activity and, consequently, growth
      cone collapse. The actin-bundling protein fascin was also inactivated,
      contributing to the destabilization and collapse of actin filaments. These
      results identify a bifunctional signaling mechanism by which proNGF regulates
      actin dynamics to acutely modulate neuronal morphology.

PMID- 22155787
TI  - The SH2 domain-containing proteins in 21 species establish the provenance and
      scope of phosphotyrosine signaling in eukaryotes.
AB  - The Src homology 2 (SH2) domains are participants in metazoan signal
      transduction, acting as primary mediators for regulated protein-protein
      interactions with tyrosine-phosphorylated substrates. Here, we describe the
      origin and evolution of SH2 domain proteins by means of sequence analysis from 21
      eukaryotic organisms from the basal unicellular eukaryotes, where SH2 domains
      first appeared, through the multicellular animals and increasingly complex
      metazoans. On the basis of our results, SH2 domains and phosphotyrosine signaling
      emerged in the early Unikonta, and the numbers of SH2 domains expanded in the
      choanoflagellate and metazoan lineages with the development of tyrosine kinases,
      leading to rapid elaboration of phosphotyrosine signaling in early multicellular
      animals. Our results also indicated that SH2 domains coevolved and the number of
      the domains expanded alongside protein tyrosine kinases and tyrosine
      phosphatases, thereby coupling phosphotyrosine signaling to downstream signaling
      networks. Gene duplication combined with domain gain or loss produced novel SH2
      containing proteins that function within phosphotyrosine signaling, which likely
      have contributed to diversity and complexity in metazoans. We found that intra-
      and intermolecular interactions within and between SH2 domain proteins increased
      in prevalence along with organismal complexity and may function to generate more
      highly connected and robust phosphotyrosine signaling networks.

PMID- 22155789
TI  - PDLIM2 inhibits T helper 17 cell development and granulomatous inflammation
      through degradation of STAT3.
AB  - Granuloma formation is an important host defense mechanism against intracellular
      bacteria; however, uncontrolled granulomatous inflammation is pathologic. T
      helper 17 (TH17) cells are thought to have a pathogenic role in autoimmune and
      inflammatory diseases, including in granulomas. Here, we report that the PDZ-LIM
      domain protein PDLIM2 inhibited TH17 cell development and granulomatous responses
      by acting as a nuclear ubiquitin E3 ligase that targeted signal transducer and
      activator of transcription 3 (STAT3), a transcription factor critical for the
      commitment of naive CD4+ T cells to the TH17 lineage. PDLIM2 promoted the
      polyubiquitination and proteasomal degradation of STAT3, thereby disrupting STAT3
      mediated gene activation. Deficiency in PDLIM2 resulted in the accumulation of
      STAT3 in the nucleus, enhanced the extent of TH17 cell differentiation, and
      exacerbated granuloma formation. This study delineates an essential role for
      PDLIM2 in inhibiting TH17 cell-mediated inflammatory responses by suppressing
      STAT3 signaling and provides a potential therapeutic target for the treatment of
      autoimmune diseases.

PMID- 22155790
TI  - Reality of the NHS budget squeeze.

PMID- 22155788
TI  - Protein kinase C eta is required for T cell activation and homeostatic
      proliferation.
AB  - Protein kinase C eta (PKCeta) is abundant in T cells and is recruited to the
      immunological synapse that is formed between a T cell and an antigen-presenting
      cell; however, its function in T cells is unknown. We showed that PKCeta was
      required for the activation of mature CD8+ T cells through the T cell receptor.
      Compared with wild-type T cells, PKCeta-/- T cells showed poor proliferation in
      response to antigen stimulation, a trait shared with T cells deficient in
      PKCtheta, which is the most abundant PKC isoform in T cells and was thought to be
      the only PKC isoform with a specific role in T cell activation. In contrast, only
      PKCeta-deficient T cells showed defective homeostatic proliferation, which
      requires self-antigen recognition. PKCeta was dispensable for thymocyte
      development; however, thymocytes from mice doubly deficient in PKCeta and
      PKCtheta exhibited poor development, indicating some redundancy between the PKC
      isoforms. Deficiency in PKCeta or PKCtheta had opposing effects on the relative
      numbers of CD4+ and CD8+ T cells. PKCeta-/- mice had a higher ratio of CD4+ to
      CD8+ T cells compared to that of wild-type mice, whereas PKCtheta-/- mice had a
      lower ratio. Mice deficient in both isoforms exhibited normal cell ratios.
      Together, these data suggest that PKCeta shares some redundant roles with
      PKCtheta in T cell biology and also performs nonredundant functions that are
      required for T cell homeostasis and activation.

PMID- 22155791
TI  - More "responsible" science reporting is needed, Leveson inquiry hears.

PMID- 22155792
TI  - US health secretary overrules FDA's decision to increase access to emergency
      contraceptive.

PMID- 22155793
TI  - Government will invest in research and innovation to stimulate UK economy.

PMID- 22155794
TI  - Novel protective lead shield and pulse fluoroscopy can reduce radiation exposure
      during the ERCP procedure.
AB  - BACKGROUND/AIMS: ERCP-related procedures involve radiation exposure of patients
      and medical staff. We developed a novel protective lead shield which is attached
      around the fluoroscopy generator. Here we examine levels of radiation exposure to
      patients, endoscopists and assistants, and evaluate the usefulness of the newly
      designed protective shield. METHODOLOGY: Four-hundred and seventy-one ERCP
      procedures were performed from April 2006 to April 2007. At first, we compared
      the radiation dose of consecutive fluoroscopy conditions with pulse fluoroscopy
      of 15 per second and then the radiation dose with and without the protective
      shield. Next, we measured the radiation exposure of endoscopists and assistants
      in the clinical setting monitored by digital dosimeter during ERCP procedure.
      RESULTS: The radiation dose was the most at the 45 degrees  direction. Using
      pulse fluoroscopy of 15 per second the radiation dose of patients and
      endoscopists decreased by about half. Using both pulse fluoroscopy of 15 per
      second and the protective shield, the radiation dose at the endoscopist's
      position was reduced up to 97%. The total fluoroscopy time was 5851 minutes in
      the 471 ERCP cases. Using pulse 15 and the protective lead shield, the radiation
      exposure dose of one endoscopist and two assistants were 2430.8, 2673.9 and
      1375.0uSv, respectively. CONCLUSIONS: Novel protective lead shield in combination
      with pulse fluoroscopy can significantly reduce the radiation exposure leading to
      avoid unnecessary radiation exposure to patients and medical staff.

PMID- 22155795
TI  - Mucinous tumors of the ovary: diagnostic challenges at frozen section and
      clinical implications.
AB  - OBJECTIVE: Frozen section (FS) diagnosis of mucinous tumors of the ovary can be
      quite difficult due to the size of these tumors, heterogeneity and potential risk
      of metastasis from gastrointestinal (GI) neoplasms. Given the paucity of data on
      this subject, our objective was to determine the reliability of FS diagnosis in
      ovarian mucinous tumors. METHODS: A retrospective review of 73 consecutive
      ovarian mucinous tumors submitted for frozen section (FS) evaluation between
      January 2004 and November 2009 was conducted. FS and final pathology results, in
      addition to patient characteristics, were collected. Univariate analysis was
      performed evaluating predictors of FS reliability. RESULTS: The average tumor
      size was 19.7cm (0.8-50cm). The FS and final pathology diagnosis were concordant
      in 66% (48/73) of the cases. Of the 25 (34%) discordant cases, 8 (11%) were
      downgraded and 17 cases (23%) were upgraded. Of the 44 tumors interpreted as LMP
      on FS, 14 (32%) were malignant at final diagnosis (26% ovarian, 7% GI) and 8
      (18%) were benign. Of the 23 benign tumors on FS, 13% were upgraded to either LMP
      or malignant at final diagnosis. Tumors with a malignant diagnosis on FS were
      100% concordant with final diagnosis. Univariate analysis did not reveal any
      correlation with the FS diagnosis and patient age, tumor size or presence of
      bilateral disease. CONCLUSIONS: Our study showed a 34% rate of discordance
      between FS and final diagnosis. Given that 5 cases (7%) were of GI origin,
      intraoperative assessment of the appendix should be performed in all mucinous
      ovarian tumors.

PMID- 22155796
TI  - Karyometry in atypical endometrial hyperplasia: a Gynecologic Oncology Group
      study.
AB  - OBJECTIVES: Treatment for atypical endometrial hyperplasia (AEH) is based on
      pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. This
      study's objective is to derive an objective characterization of nuclei from cases
      diagnosed as AEH or superficially invasive endometrial cancer (SIEC). METHODS:
      Cases from GOG study 167A were classified by a central pathology committee as AEH
      (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were
      recorded. Features of the nuclear chromatin pattern were computed. Classification
      rules were derived by discriminant analysis. RESULTS: Nuclei from cases of AEH
      and SIEC occupy the same range on a progression curve for endometrial lesions.
      Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic
      characteristics and premalignant/neoplastic characteristics. The principal
      difference between AEH and SIEC is the percentage of premalignant/neoplastic
      nuclei. When this percentage approaches 50-60% superficial invasion is likely.
      SIEC may develop already from lesions at the low end of the progression curve.
      CONCLUSIONS: AEH comprises cases which may constitute a low risk group involving
      <40% of AEH cases. These cases hold a percentage of <20% of nuclei of a
      preneoplastic phenotype. AEH cases from the central and high end of progression
      have >40% of nuclei of preneoplastic phenotype. Nuclei of the preneoplastic
      phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where
      this percentage exceeds 60%. The percentage of nuclei of the preneoplastic
      phenotype in AEH esions might serve as criterion for assessment of risk for the
      development of invasive disease.

PMID- 22155797
TI  - A study of symptoms described by ovarian cancer survivors.
AB  - OBJECTIVE: A cross-sectional, observational study to evaluate physical and
      psychological symptoms experienced by patients following completion of treatment
      for ovarian cancer and compared to symptoms documented in their hospital notes.
      METHODS: Women attending follow-up clinic at Hammersmith Hospital having
      undergone treatment for primary or relapsed ovarian cancer were asked to complete
      two validated questionnaires (EORTC QLQ-C30 and QLQ-OV28) and a "wellbeing
      thermometer". Results were assessed and stratified by patient age, tumour stage,
      relapse status, type of chemotherapy received and treatment-free interval.
      Symptoms reported in questionnaires were compared to those documented in
      patients' hospital notes. RESULTS: Of 116 women approached, 100 (86%)
      participated in this study and had received chemotherapy for ovarian cancer
      between 2003 and 2010. The most frequently described and severe symptoms reported
      in the questionnaires were emotional symptoms, negative feelings about treatment
      or prognosis, fatigue and pain. Dyspareunia, cognitive impairment and peripheral
      neuropathy were also frequently described. Symptom severity was independent of
      variables such as disease stage, type of chemotherapy received and relapse
      status. The "wellbeing thermometer" scores closely correlated with pain, fatigue,
      weakness, gastrointestinal symptoms and attitude to disease or treatment
      (p<0.001). There was a marked discordance between questionnaire-reported symptoms
      and those recorded in hospital notes. CONCLUSIONS: The majority of women surveyed
      experienced persistent psychological and physical symptoms following ovarian
      cancer treatment; in particular: psychological concerns, sexual inactivity and
      fatigue, all potentially reversible with appropriate interventions. Our results
      highlight the extent of symptoms described by ovarian cancer survivors and the
      need for them to be adequately acknowledged and addressed.

PMID- 22155798
TI  - Estimation of sedimentation rate in the Middle and South Adriatic Sea using
      137Cs.
AB  - (137)Cs activity concentrations were studied in the sediment profiles collected
      at five locations in the Middle and South Adriatic. In the sediment profiles
      collected from the South Adriatic Pit, the deepest part of the Adriatic Sea, two
      (137)Cs peaks were identified. The peak in the deeper layer was attributed to the
      period of intensive atmospheric nuclear weapon tests (early 1960s), and the other
      to the Chernobyl nuclear accident (1986). Those peaks could be used to estimate
      sedimentation rates by relating them to the respective time periods. Grain-size
      analysis showed no changes in vertical distribution through the depth of the
      sediment profile, and these results indicate uniform sedimentation, as is
      expected in deeper marine environments. It was not possible to identify
      respective peaks on more shallow locations due to disturbance of the seabed
      either by trawlers (locations PalagruZa and Jabuka) or by river sediment
      (location Albania). The highest sedimentation rates were found in Albania (~4 mm
      y(-1)) and Jabuka (3.1 mm y(-1)). For PalagruZa, the sedimentation rate was
      estimated to be 1.8 mm y(-1), similar to the South Adriatic Pit where the
      sedimentation rate was estimated to be 1.8+/-0.5 mm y(-1). Low sedimentation
      rates found for the Middle and South Adriatic Sea are consistent with previously
      reported results for the rest of the Mediterranean.

PMID- 22155799
TI  - An assessment of the radiological scenario around uranium mines in Singhbhum East
      district, Jharkhand, India.
AB  - The present work deals with the prevalent radiological scenario around uranium
      mining sites in the Singhbhum East district of Jharkhand state, India. The
      concentration of naturally occurring radioactive materials (NORMs) was estimated
      from 27 soil samples collected around three regions in the study area, namely
      Bagjata, Turamdih and Jaduguda. The mean activity concentrations of (238)U in
      Bagjata, Turamdih and Jaduguda regions were found to be 128.6, 95.7 and 49.2 Bq
      kg(-1), respectively. Similarly for (232)Th and (40)K the activity concentrations
      were found to be 57.3, 78.4, 68.9 and 530, 425 and 615 Bq kg(-1) in the Bagjata,
      Turamdih and Jaduguda regions, respectively, which are comparable with other
      reported values worldwide, except for some high values. The calculated gamma dose
      rate, obtained from the concentrations of (238)U, (232)Th and (40)K in the
      samples, was compared with the observed dose rate in air. A good correlation
      (0.96) was observed between the calculated and the observed gamma dose rate. The
      annual outdoor effective dose rate was estimated and the values falls between
      0.04-0.3, 0.07-0.3 and 0.07-.14 mSv y(-1) with mean values of 0.14, 0.12 and 0.11
      mSv y(-1) for the Bagjata, Turamdih and Jaduguda regions, respectively. The
      terrestrial dose rates in all the three regions are comparable with other
      reported values worldwide, except for a few high values in Greece, Rio Grande Do
      Norte (Brazil) and Kalpakkam (India).

PMID- 22155801
TI  - Total knee arthroplasty with NexGen legacy posterior stabilized.
AB  - Total knee arthroplasty (TKA) has been primarily devised for pain free range of
      movement near physiological demands and even take part in sports and leisure
      interests along with day to day activities. Therefore we conducted an assessment
      on the performance of our patients after 5 years of followup.  Total of 94
      patients ranging from an age group of 38 to 75 years with pathologies of
      osteoarthritis, rheumatoid arthritis and post traumatic arthritis were subjected
      to implantation in our institution and included in this restrospective study. All
      patients were implanted with NexGen Legacy Posterior Stabilisied (LPS) system. 
      The results have been drawn on the basis of the clinical performance and
      radiographic analysis with a follow up of upto 5 years. Knee society score
      increase from Preoperatively 60 to postoperatively 85, Knee functional score
      increase from preoperatively 55 to postoperatively 100. No cases of patella clunk
      syndrome or patella dislocation were observed in our patients.  The final
      clinical results of operative treatment with Nexgen LPS system after 5 years of
      follow-up of patients corresponding to daily approved International scoring
      system. All of this indicates the advantages of this system comparing to its
      other daily analogues.

PMID- 22155800
TI  - [Modern aspects of surgical treatment with gastroesophageal  reflux desease: our
      experience and literature review].
AB  - It is presented our experience and review of literature of pathogenesis,
      symptomatology, diagnostics and surgical treatment of gastroesophageal reflux
      desease (GERD). A cohort of 104 patients (67 males and 37 females, median age -
      42.5) who underwent "open" A. Chernousov modified Nissen fundoplication was
      evaluated for an follow-up period more than 10 years. In 23 cases with
      concomitant duodenal ulcer and gastric hypersecretion selective proximal vagotomy
      additionally was performed, 3 of them also underwent cholecistectomy and in 1
      case - splenectomy because of spleen lymphoma. There were no mortality or major
      perioperative complication (1 case of iatrogenic splenectomy) in our series. Only
      9 patients have transient episodes of mild dysphagia. Postoperative endoscopy an
      X-Ray revealed a good swallow and functional status of esophagus and stomach. The
      good and excellent results were achieved in more 90% of cases. No
      reinterventional surgery was needed.

PMID- 22155802
TI  - Combined development of thyroid gland and reproductive system benign diseases.
AB  - The aim of the study is to establish the role of endocrine disturbances in
      development of malignant tumors in patients with thyroid gland and reproductive
      system pathology.   We studied 207 patients with synchronic and metachronic
      development of thyroid gland and reproductive system benign tumors. The patients'
      average age was 35-58 years.   According to study the following aspects were
      determined: clinical and hormonal aspect of thyroid gland and reproductive system
      benign tumor disease coincidence, analyses of thyroid gland and reproductive
      system pre-cancer disease pathogenesis, neuroendocrine relations-like increased
      thyrotrophic hormone secretion causes strengthening of prolactin secretion, which
      depresses luteinizing hormone release and increases production of follicular
      stimulating hormone.   It has been proved that fibromyomas absolute
      hyperestrogenemia which develops during hypersecretion of follicular stimulating
      hormone (FSH) plays a role in etiology of uterine Gonadoliberin hypersecretion,
      especially follicular stimulating hormone FSH and corpus luteum deficiency is
      very important in development of ovarian pre-cancer and cancer diseases.

PMID- 22155803
TI  - Endovascular treatment of patients with chronic cerebrospinal venous
      insufficiency and multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system (CNS) by an unknown pathogenesis. MR venography and postmortem
      studies have demonstrated a topographic correspondence between multiple sclerosis
      (MS) plaques and the cerebral venous system pathology. In recent observational
      studies performed on patients from distinctive gene pools, the prevalence of
      chronic cerebrospinal venous insufficiency (CCSVI) in MS ranged from 56% to 100%.
      Endovascular treatment (percutaneous transluminal angioplasty (PTA) with or
      without stenting) of CCSVI was reported to be feasible with a minor complication
      rate. In 4 patients with different forms of multiple sclerosis venography was
      performed that revealed stenosis of the proximal region of the jugular vein
      (right or left). Percutaneous transluminal balloon angioplasty (PTA) was
      performed in all patients. There were no complications and mean stenosis was
      reduced after PTA from 59.75% to 36.75%. Follow-up included clinical observations
      and magnetic resonance imaging (MRI). In all the cases we observed positive
      remission of the disease, the first ever documented case of MRI index
      improvement. PTA seems to be an effective treatment for patients with CCVI and
      multiple sclerosis, However, randomized studies are warranted to establish the
      efficacy of this new treatment for MS.

PMID- 22155804
TI  - [Ultrasound in complex of radiological studies in diagnosis of ankle joint medial
      aspect pathologies].
AB  - The aim of the research is to study sonosemiotics of ankle joint pathology by
      means of ultrasound in order to optimize the diagnostic process and improve the
      treatment. 130 patients (age ranges from 5 to 70 years) underwent the
      radiological study of ankle joint medial aspect. Pathology types: degenerative
      dystrophic diseases - 39 (30%), inflammatory pathology - 21 (16.2%), traumatic
      injuries - 20 (15.2%), vascular pathologies - 26 (20%), neurogenic problems -7
      (5.4%), soft tissue neoplasms - 5 (3.8%), congenital anomalies - 7 (5.4%) and
      vertebral pathology - 5 (4.0%). The diagnostic studies include: a) Ultrasound,
      performed on digital ultrasound system using high frequency (7.5-12.0 MHz) linear
      probe with Doppler capability (all patients); b) X-Ray filming in antero
      posterior and lateral projections (6 patients- 4.5%); c) MRI - T1 and T2 weighted
      images in saggital and transverse planes 10 patients (10.0%) and d) CT - 2
      patients (1.5%); To 2 (1.5%) patient biopsy has been performed. This study showed
      that ultrasound was successful in ankle joint medial aspect pathology diagnosis
      in 108 cases (84.0%); It was ineffective in osseous pathology definition. In
      final diagnosis of impingment syndrom MRI was required in 4 (3.6%) cases. It is
      concluded that ultrasound should be used as a Gold Standard in diagnosis of
      localized pain and swelling in the ankle joint.

PMID- 22155805
TI  - [Assessment of psoriatic nail lesions therapy by means of nail psoriasis severity
      index].
AB  - The problem of psoriatic nail lesions is known for a long time. According to
      various authors, psoriatic onychodystrophy has been diagnosed in 15-78% of
      patients with psoriasis. At the same time, we know that the treatment of
      psoriatic nail lesions is not always successful.   The aim of the study was to
      evaluate the therapeutic efficacy of the drug onypso in the complex treatment of
      patients with psoriasis by means of NAPSI index.  We observed 39 patients with
      psoriasis (20 men and 19 women at the age of 19 to 65 years with disease duration
      of 1 year to 25 years). The distribution of clinical manifestations of psoriatic
      onychodystrophy was as follow: thimble symptom -150 plates, subungual
      hyperkeratosis lesion type - 90 plates, onycholysis lesion type was observed in
      50 plates.   As a systemic treatment we used the cytostatic agent methotrexate -
      parenteral administration of 25 mg (once a week). In duration of total treatment
      course the patient received 90 -120 mg. Local treatment was provided by means of
      varnish onypso (once a day for 6 months).   The survey revealed that at 7 weeks
      of treatment there was a 25 % reduction of initial value of NAPSI index, at the
      end of 14 weeks of therapy the above mentioned index was reduced for 50 % and at
      the 24 weeks for 75% respectively. It should be noted, that resolution of the
      cutaneous pathology was much faster than improvement of the structure of affected
      nail plates. Thus, drug onypso proposed for the specific treatment of nail
      lesions used in the complex therapy of patients with psoriasis is simple in use,
      accessible, compliant and highly effective.  As a conclusion, we can say that
      NAPSI method, used to determine the extent of lesions and the effectiveness of
      the therapy, can objectively evaluate the dynamics of clinical pathology of the
      nails and adequacy of used treatment.

PMID- 22155806
TI  - Fasting insulin and HOMA-index changes in patients treated with valproic acid.
AB  - Our study was carried out to ascertain the role of valproic acid for inducing
      metabolic disorders like hyperinsulinemia, insulin resistance and metabolic
      syndrome.   Seventy-nine subjects were enrolled into the study. They were divided
      in 3 groups: 26 patients with epilepsy on VPA monotherapy and 28 patients with
      epilepsy on CBZ monotherapy and 25 healthy controls. Blood samples for fasting
      insulin, glucose, C-peptide, TG and HDL were collected. We compared insulin, C
      peptide, C-peptide/insulin ratio, HOMA-IR, BMI, central obesity and metabolic
      syndrome in patients treated with VPA, patients treated with CBZ and in healthy
      controls.   VPA treatment was associated with insulin resistance (30.8%) in
      opposite to CBZ treatment (7.1%). Metabolic syndrome existed in 34,6%, 14,3% and
      12% among VPA, CBZ and control groups, respectively. There was no difference in C
      peptide/insulin ratio between study groups. Interestingly lean VPA treated
      patients showed high frequency of insulin resistance and metabolic syndrome
      compared to lean CBZ treated patients and controls. Therefore we suppose that
      obesity should not be an obligatory factor for VPA induced metabolic
      disturbances.   VPA treatment is associated with insulin resistance and metabolic
      syndrome. This metabolic disorders were not connected with diminished hepatic
      insulin extraction. Although VPA treated patients showed central obesity
      predominance, we suggest that VPA can induce such metabolic and endocrine changes
      without obesity.

PMID- 22155807
TI  - [Evaluation of endoscopic changes in pationts with sarcoidosis of respiratory
      organs].
AB  - The aim of the study was to reveal endoscopic changes of a bronchial tree in
      patients with sarcoidosis of respiratory organs with apply endobronchial
      microsurgical biopsy interventions.  Under our supervision there were 57 patients
      with various forms intrathoracic sarcoidosis.   The character of endobronchial
      displays of disease and changes of mucous bronchial tubes are depicted.

PMID- 22155808
TI  - [Physiological basics of sport activity of professional football players].
AB  - Maintenance of motor activity by autonomic nervous system is adjusted, mainly, by
      congenital reflexes. But alongside with inborn reactions to muscular work at
      formation of motor skill the specific vegetative components are formed to the
      given kind of sport activity.  The aim of our research was revealing those
      physiological features which are characteristic for an organism of the high
      skilled sportsmen, with large experience of training and competitive activity. 
      At tested football players have been measured some parameters of external
      respiration and cardiovascular system.  In our investigation it is shown, that
      programming of the same productivity of work and the same effect are achieved by
      unequal vegetative support and a different combination of separate components of
      the general vegetative reaction. Definition and a due estimation of these
      intermediate parameters in conditions of rest and at physical loading enables
      objective judgement about a functional condition of the sportsman, about weak
      parts in system of maintenance of a homeostasis of an organism and directions of
      accomplish the functioning of the basic effectors.

PMID- 22155809
TI  - [Development of medical tourism in Georgia. Problems and prospectiv (review)].
AB  - Medical tourism is the movement of patients through a global network of health
      services. Medical tourists seek affordable healthcare on a timely basis in a
      variety of destination nations. The expansion of global medical services has
      sparked immense economic growth in developing nations and has created a new
      market for advertising access to care. Beyond offering a unique untapped market
      of services, medical tourism has invited a host of liability, malpractice and
      ethical concerns. The explosion of off-shore "mini-surgical" vacations will
      surely incite global unification and increased access, quality and affordability
      of care.   Medical tourism is a dynamic subset of global health care that
      incorporates a variety of services, procedures and venues of care. Health
      insurance coverage, the impact on domestic and global markets, and the use of
      international standards of care will be examined in combination with quality,
      access and cost parameters. The global nature of medical tourism invites a
      variety of legal and ethical issues and calls for an organizational body to
      monitor this new phenomenon. Finally, the future implications of the
      globalization of health services and systems will be discussed.

PMID- 22155810
TI  - [Neutropenia in children].
AB  - Neutropenia in children is defined as decrease in absolute number of neutrophils
      to 1x 10(9)/l. This condition is common, its course is mild and usually
      transient, though persistent, severe, chronic forms also encounter in clinical
      practice. In such cases the prognosis is not always favorable. Causes of
      neutropenia could not always be identified. In the most cases it is caused by
      infection (bacterial, viral, etc), consumption of drugs, nutrient deficiency and
      others. There are also hereditary and congenital forms. Neutropenia in childhood
      is mostly met during the first 24 months of life and has specific clinical
      manifestations; therefore it is challenging to make a diagnosis. The presented
      work describes findings of observation over three pediatric patients, in whom
      persistent, severe neutropenia was manifested up to one year of age. Based on
      case history, clinical and para-clinical data analysis and catamnestic
      observation benign chronic neutropenia was diagnosed in two cases and primary
      autoimmune neutropenia - in one. The observation is in progress.

PMID- 22155811
TI  - [Role of the adipose derived adult stem cell in cartilage regeneration, features
      and brief history (review)].
AB  - Regeneration of the cartilage is one of the difficult and uncertain solved
      problems of reconstructive surgery. Lot of successfully experiments was done
      about regeneration of cartilage defects with ADAS cells. Use of stem cells
      promise new decisons in this direction at the near future. Little information
      about ADAS cells and their use in regeneration of cartilage defects was revealed.

PMID- 22155812
TI  - [Chronic psychogenic stress as a factor of formation depressive behavior in
      rats].
AB  - The problem of adequate animal model of depression still remains. In our
      experiments depression-like condition on white rats were reached by the chronic
      stressors of psychogenic nature. Stress was carried out in a modified shuttle
      chamber of active avoidance. At the very beginning of the study (the first stage
      of stress) an animal was forced to develop a reaction of active avoidance on
      metronome beats (2 Hz), later, after its fixation, the same reaction was
      developed on tone (500 Hz). Then simultaneous testing of two developed reactions
      of active avoidance was performed (the second stage of stress). The simultaneous
      testing of active avoidance in rats is a difficult task and on the first day of
      the experiment the number of the right answers doesn't exceed 5-30 % that is
      stable and does not reach the criteria (80-100%) on the antidepressant
      fluoxetine. At the second stage of stress, increased motor activity, duration and
      number of vertical supports, inter-signal transitions in rats, which is even more
      increased on the background of antidepressant flueksetine. At this stage, in the
      "open field - OF" test statistically significantly reduced motor and research
      activity (number of crossed squares) and latency of motor activity. Reduced
      mobility of the animals in tests of "forced swim - FST" and "tail suspension test
      - TST" was not statistically significant. After the long-term application of
      stressors (35-48 days, III stage of stress) animals showed decreased motor
      activity in the "OF" test, decreased mobility in "FST" and "TST", changes being
      statistically valid. All behavioral changes indicating depression-like condition
      in animals were normalized after per os administration of antidepressant
      Fluoxetine at doses of 40 mg/kg. For those that were in a two-week "rest"
      (eliminating stressors within 14 days) and did not receive pharmacological
      preparations, improvements were not observed.

PMID- 22155813
TI  - Biological active compounds from Georgian Galanthus shaoricus.
AB  - Amaryllidaceae alkaloids exhibit antitumour, antiviral and anticholinergic
      activities. Some of them have been used in the treatment of myasthenia gravis,
      myopathy and diseases of the nervous system. In this study, the characterization
      of these compounds from Amaryllidaceae plants along with some biological
      activities and some regulations to conserve the native flora will be reviewed. 
      Plants materials: Galanthus shaoricus Kem.-Nath., were collected in 2007-2008
      during the flowering period in Georgia. The preparation of extracts and fractions
      were obtained using methanolic maceration. Crude alkaloidal extracts were
      typically purified by liquid-liquid partitioning of their basic forms in
      chloroform. Lycorine, galantamine and tazettine has been found as one of the
      major alkaloid from Amaryllidaceae plants.   Galanthus shaoricus have shown good
      antimalarial and cytotoxic activity in a dose-dependent manner. Methanolic
      extracts from bulbs demonstrated significant growth inhibition on human Hela and
      HCT-116 cells lines with IC50 (MUg/mL) 16.3+/-1.8; 22.1+/-2.9 (aerial parts) and
      12.8+/-1.7; 16.5+/-1.9 (Bulbs), respectively.   Concerning the Amaryllidaceae
      alkaloids, lycorine with IC50 (MUM) 0.8+/-0.5 and 2.6+/-0.2, haemantaimene
      (IC50=1.1+/-0.7 and 2.7+/-0.8 MUM), hamaine (IC50=3.4+/-1.0 and 6.2 +/-1.4 MUM),
      homolycorine (IC50=1.4+/-0.9 and 3.3+/-1.0 MUM), hipeastrine (IC50=2.8+/-1.0 and
      7.5+/-1.8 MUM) were found to be responsible for the cytotoxic activity on HCT-116
      and Hela cell lines, respectively.

PMID- 22155814
TI  - Antioxidant polyphenols from Populus alba growing in Georgia.
AB  - The aim of the study was to evaluate natural antioxidant properties of Populus
      alba. The antioxidant effects in plants are mainly due to the presence of
      phenolic compounds such as flavonoids, phenolic acids, tannins and phenolic
      diterpenes. Oxidative damage is implicated in most diseases processes. In vitro
      studies are able to demonstrate for flavonols and flavones a considerable
      antioxidative activity, mainly based on scavenging of oxygen radicals. The
      antioxidative potential of different fractions (respective organic fractions of n
      hexane, chloroform and ethyl acetate) of 70% methanol extract of Populus alba was
      evaluated using free radical-scavenging activity on DPPH (1,1-diphenyl-2
      picrylhydrazyl ) assays. The methanol extract showed significant (p<0.05)
      activities in all antioxidant assays and contained a high level of total phenolic
      content. It was observed that the level of hydrophilic phenolic content was
      higher than that of hydrophobics. Among those organic solvent fractions, ethyl
      acetate fraction exhibited significant activities due to the highest level of
      total phenolic content and their IC50 values were 0.18+/-0.02 mg/mL, 0.26+/
      0.03mg/mL and 0.28+/-0.02 mg/mL in DPPH, respectively. These activities were
      superior to those of a commercial natural antioxidants tested. The chloroform and
      hexan fractions also exhibited significant (p<0.05) free radical-scavenging
      activity, attributed to the high amount of hydrophilic phenolics.

PMID- 22155815
TI  - Pharmacokinetics and pharmacodynamics of TMC207 and its N-desmethyl metabolite in
      a murine model of tuberculosis.
AB  - TMC207 is a first-in-class diarylquinoline with a new mode of action against
      mycobacteria targeting the ATP synthase. It is metabolized to an active
      derivative, N-desmethyl TMC207, and both compounds are eliminated with long
      terminal half-lives (50 to 60 h in mice) reflecting slow release from tissues
      such as lung and spleen. In vitro, TMC207 is 5-fold more potent against
      Mycobacterium tuberculosis than N-desmethyl TMC207, and the effects of the two
      compounds are additive. The pharmacokinetic and pharmacodynamic (PK-PD) response
      was investigated in the murine model of tuberculosis (TB) infection following
      oral administration of different doses of TMC207 or N-desmethyl TMC207 at 5 days
      per week for 4 weeks starting the day after intravenous infection with M.
      tuberculosis and following administration of different doses of TMC207 at various
      dosing frequencies for 6 weeks starting 2 weeks after infection. Upon
      administration of N-desmethyl TMC207, maximum plasma concentration (C(max)), area
      under the plasma concentration-time curve from time zero to 168 h postdose
      (AUC(168h)), and minimum plasma concentration (C(min)) were approximately dose
      proportional between 8 and 64 mg/kg, and the lung CFU counts were strongly
      correlated with these pharmacokinetic parameters using an inhibitory sigmoid
      maximum effect (E(max)) model. Administration of the highest dose (64 mg/kg)
      produced a 4.0-log(10) reduction of the bacillary load at an average exposure
      (average concentration [C(avg)] or AUC(168h) divided by 168) of 2.7 MUg/ml. Upon
      administration of the highest dose of TMC207 (50 mg/kg) 5 days per week for 4
      weeks, the total reduction of the bacillary load was 4.7 log(10). TMC207 was
      estimated to contribute to a 1.8-log(10) reduction and its corresponding exposure
      (C(avg)) was 0.5 MUg/ml. Optimal bactericidal activity with N-desmethyl TMC207
      was reached at a high exposure compared to that achieved in humans, suggesting a
      minor contribution of the metabolite to the overall bactericidal activity in TB
      infected patients treated with TMC207. Following administration of TMC207 at a
      total weekly dose of 15, 30, or 60 mg/kg fractionated for either 5 days per week,
      twice weekly, or once weekly, the bactericidal activity was correlated to the
      total weekly dose and was not influenced by the frequency of administration.
      Exposures (AUC(168h)) to TMC207 and N-desmethyl TMC207 mirrored this dose
      response, indicating that the bactericidal activity of TMC207 is concentration
      dependent and that AUC is the main PK-PD driver on which dose optimization should
      be based for dosing frequencies up to once weekly. The PK-PD profile supports
      intermittent administration of TMC207, in agreement with its slow release from
      tissues.

PMID- 22155816
TI  - Identification, characterization, and recombinant expression of epidermicin NI01,
      a novel unmodified bacteriocin produced by Staphylococcus epidermidis that
      displays potent activity against Staphylococci.
AB  - We describe the discovery, purification, characterization, and expression of an
      antimicrobial peptide, epidermicin NI01, which is an unmodified bacteriocin
      produced by Staphylococcus epidermidis strain 224. It is a highly cationic,
      hydrophobic, plasmid-encoded peptide that exhibits potent antimicrobial activity
      toward a wide range of pathogenic Gram-positive bacteria including methicillin
      resistant Staphylococcus aureus (MRSA), enterococci, and biofilm-forming S.
      epidermidis strains. Purification of the peptide was achieved using a combination
      of hydrophobic interaction, cation exchange, and high-performance liquid
      chromatography (HPLC). Matrix-assisted laser desorption ionization-time of flight
      (MALDI-TOF) analysis yielded a molecular mass of 6,074 Da, and partial sequence
      data of the peptide were elucidated using a combination of tandem mass
      spectrometry (MS/MS) and de novo sequencing. The draft genome sequence of the
      producing strain was obtained using 454 pyrosequencing technology, thus enabling
      the identification of the structural gene using the de novo peptide sequence data
      previously obtained. Epidermicin NI01 contains 51 residues with four tryptophan
      and nine lysine residues, and the sequence showed approximately 50% identity to
      peptides lacticin Z, lacticin Q, and aureocin A53, all of which belong to a new
      family of unmodified type II-like bacteriocins. The peptide is active in the
      nanomolar range against S. epidermidis, MRSA isolates, and vancomycin-resistant
      enterococci. Other unique features displayed by epidermicin include a high degree
      of protease stability and the ability to retain antimicrobial activity over a pH
      range of 2 to 10, and exposure to the peptide does not result in development of
      resistance in susceptible isolates. In this study we also show the structural
      gene alone can be cloned into Escherichia coli strain BL21(DE3), and expression
      yields active peptide.

PMID- 22155817
TI  - Ethambutol pharmacokinetic variability is linked to body mass in overweight,
      obese, and extremely obese people.
AB  - We conducted a prospective study of 18 adult volunteers (male-to-female ratio of
      1) whose body mass index fell into categories of <25, 25 to 40, or >40 kg/m(2),
      who received a single oral dose of 1,600 mg ethambutol. Only individuals with
      normal renal function were recruited. The minimum body mass (M) was 45.6 kg, the
      median was 90.8 kg, and the maximum weight was 160.4 kg. Ethambutol
      pharmacokinetics were best described by a two-compartment model. Inclusion of
      weight as a covariate dramatically improved the model, with a relative likelihood
      approaching infinity. The typical clearance was 42.6 liters/h. Ethambutol
      systemic clearance was proportional to (M/45.6)(3/4) and thus obeyed fractal
      geometry-based laws. This means that the area under the concentration-time curve
      (AUC) actually decreased for obese patients compared to that for leaner patients,
      reducing chances of concentration-dependent toxicity. On the other hand, such
      reduced AUCs could lead to therapy failure. Thus, new and individualized
      ethambutol dosing regimens need to be designed for obese and extremely obese
      patients.

PMID- 22155818
TI  - Characterization of nasal and blood culture isolates of methicillin-resistant
      Staphylococcus aureus from patients in United States Hospitals.
AB  - A total of 299 nares and 194 blood isolates of methicillin-resistant
      Staphylococcus aureus (MRSA), each recovered from a unique patient, were
      collected from 23 U.S. hospitals from May 2009 to March 2010. All isolates
      underwent spa and staphylococcal cassette chromosome mec element (SCCmec) typing
      and antimicrobial susceptibility testing; a subset of 84 isolates was typed by
      pulsed-field gel electrophoresis (PFGE) using SmaI. Seventy-six spa types were
      observed among the isolates. Overall, for nasal isolates, spa type t002-SCCmec
      type II (USA100) was the most common strain type (37% of isolates), while among
      blood isolates, spa type t008-SCCmec type IV (USA300) was the most common (39%).
      However, the proportion of all USA100 and USA300 isolates varied by United States
      census region. Nasal isolates were more resistant to tobramycin and clindamycin
      than blood isolates (55.9% and 48.8% of isolates versus 36.6% and 39.7%,
      respectively; for both, P < 0.05). The USA300 isolates were largely resistant to
      fluoroquinolones. High-level mupirocin resistance was low among all spa types
      (<5%). SCCmec types III and VIII, which are rare in the United States, were
      observed along with several unusual PFGE types, including CMRSA9, EMRSA15, and
      the PFGE profile associated with sequence type 239 (ST239) isolates. Typing data
      from this convenience sample suggest that in U.S. hospitalized patients, USA100
      isolates of multiple spa types, while still common in the nares, have been
      replaced by USA300 isolates as the predominant MRSA strain type in positive blood
      cultures.

PMID- 22155819
TI  - Agreement assessment of tigecycline susceptibilities determined by the disk
      diffusion and broth microdilution methods among commonly encountered resistant
      bacterial isolates: results from the Tigecycline In Vitro Surveillance in Taiwan
      (TIST) study, 2008 to 2010.
AB  - The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006,
      is a nationwide surveillance program designed to longitudinally monitor the in
      vitro activity of tigecycline against commonly encountered drug-resistant
      bacteria. This study compared the in vitro activity of tigecycline against 3,014
      isolates of clinically important drug-resistant bacteria using the standard broth
      microdilution and disk diffusion methods. Species studied included methicillin
      resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant
      Enterococcus faecium (VRE; n = 191), extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n =
      736), and Acinetobacter baumannii (n = 726) that had been collected from patients
      treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone
      diameters were interpreted according to the currently recommended U.S. Food and
      Drug Administration (FDA) criteria and the European Committee on Antimicrobial
      Susceptibility Testing (EUCAST) criteria. The MIC(90) values of tigecycline
      against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A.
      baumannii were 0.5, 0.125, 0.5, 2, and 8 MUg/ml, respectively. The total error
      rates between the two methods using the FDA criteria were high: 38.4% for ESBL
      producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria,
      the total error rate was also high (54.6%) for A. baumannii isolates. The total
      error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing
      E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and
      A. baumannii against tigecycline, the broth microdilution method should be used
      because of the poor correlation of results between these two methods.

PMID- 22155820
TI  - Safe and sustained vaginal delivery of pyrimidinedione HIV-1 inhibitors from
      polyurethane intravaginal rings.
AB  - The potent antiretroviral pyrimidinediones IQP-0528 (PYD1) and IQP-0532 (PYD2)
      were formulated in polyurethane intravaginal rings (IVRs) as prophylactic drug
      delivery systems to prevent the sexual transmission of HIV-1. To aid in the
      selection of a pyrimidinedione candidate and the optimal loading of the drug in
      the IVR delivery system, four pyrimidinedione IVR formulations (PYD1 at 0.5 wt%
      [PYD1(0.5 wt%)], PYD1(1 wt%), PYD2(4 wt%), and PYD2(14 wt%)) were evaluated in
      pigtail macaques over 28 days for safety and pyrimidinedione vaginal
      biodistribution. Kinetic analysis of vaginal proinflammatory cytokines, native
      microflora, and drug levels suggested that all formulations were safe, but only
      the high-loaded PYD2(14 wt%) IVR demonstrated consistently high pyrimidinedione
      vaginal fluid and tissue levels over the 28-day study. This formulation delivered
      drug in excess of 10 MUg/ml to vaginal fluid and 1 MUg/g to vaginal tissue, a
      level over 1,000 times the in vitro 50% effective concentration. The in vitro
      release of PYD1 and PYD2 under nonsink conditions correlated well with in vivo
      release, both in amount and in kinetic profile, and therefore may serve as a more
      biologically relevant means of evaluating release in vitro than typically
      employed sink conditions. Lastly, the pyrimidinediones in the IVR formulation
      were chemically stable after 90 days of storage at elevated temperature, and the
      potent nanomolar-level antiviral activity of both molecules was retained after in
      vitro release. Altogether, these results point to the successful IVR formulation
      and vaginal biodistribution of the pyrimidinediones and demonstrate the
      usefulness of the pigtail macaque model in evaluating and screening
      antiretroviral IVR formulations prior to preclinical and clinical evaluation.

PMID- 22155821
TI  - Impact of spores on the comparative efficacies of five antibiotics for treatment
      of Bacillus anthracis in an in vitro hollow fiber pharmacodynamic model.
AB  - Bacillus anthracis, the bacterium that causes anthrax, is an agent of
      bioterrorism. The most effective antimicrobial therapy for B. anthracis
      infections is unknown. An in vitro pharmacodynamic model of B. anthracis was used
      to compare the efficacies of simulated clinically prescribed regimens of
      moxifloxacin, linezolid, and meropenem with the "gold standards," doxycycline and
      ciprofloxacin. Treatment outcomes for isogenic spore-forming and non-spore
      forming strains of B. anthracis were compared. Against spore-forming B.
      anthracis, ciprofloxacin, moxifloxacin, linezolid, and meropenem reduced the B.
      anthracis population by 4 log(10) CFU/ml over 10 days. Doxycycline reduced the
      population of this B. anthracis strain by 5 log(10) CFU/ml (analysis of variance
      [ANOVA] P = 0.01 versus other drugs). Against an isogenic non-spore-forming
      strain, meropenem killed the vegetative B. anthracis the fastest, followed by
      moxifloxacin and ciprofloxacin and then doxycycline. Linezolid offered the lowest
      bacterial kill rate. Heat shock studies using the spore-producing B. anthracis
      strain showed that with moxifloxacin, ciprofloxacin, and meropenem therapies the
      total population was mostly spores, while the population was primarily vegetative
      bacteria with linezolid and doxycycline therapies. Spores have a profound impact
      on the rate and extent of killing of B. anthracis. Against spore-forming B.
      anthracis, the five antibiotics killed the total (spore and vegetative) bacterial
      population at similar rates (within 1 log(10) CFU/ml of each other). However,
      bactericidal antibiotics killed vegetative B. anthracis faster than
      bacteriostatic drugs. Since only vegetative-phase B. anthracis produces the
      toxins that may kill the infected host, the rate and mechanism of killing of an
      antibiotic may determine its overall in vivo efficacy. Further studies are needed
      to examine this important observation.

PMID- 22155822
TI  - Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results
      of the Istanbul study.
AB  - No data on whether brucellar meningitis or meningoencephalitis can be treated
      with oral antibiotics or whether an intravenous extended-spectrum cephalosporin,
      namely, ceftriaxone, which does not accumulate in phagocytes, should be added to
      the regimen exist in the literature. The aim of a study conducted in Istanbul,
      Turkey, was to compare the efficacy and tolerability of ceftriaxone-based
      antibiotic treatment regimens with those of an oral treatment protocol in
      patients with these conditions. This retrospective study enrolled 215 adult
      patients in 28 health care institutions from four different countries. The first
      protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second
      protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and
      doxycycline. In the third protocol (P3), the patients started with P1 and
      transferred to P2 when ceftriaxone was stopped. The treatment period was shorter
      with the regimens which included ceftriaxone (4.40 +/- 2.47 months in P1, 6.52 +/
      4.15 months in P2, and 5.18 +/- 2.27 months in P3) (P = 0.002). In seven
      patients, therapy was modified due to antibiotic side effects. When these cases
      were excluded, therapeutic failure did not differ significantly between
      ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42,
      9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be
      better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite
      negative outcome (CNO; relapse plus therapeutic failure) was considered.
      Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n =
      3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens
      are more successful and require shorter therapy than the oral treatment protocol.

PMID- 22155823
TI  - Mechanism of interaction of human mitochondrial DNA polymerase gamma with the
      novel nucleoside reverse transcriptase inhibitor 4'-ethynyl-2-fluoro-2'
      deoxyadenosine indicates a low potential for host toxicity.
AB  - The potent antiretroviral 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a
      promising experimental agent for treating HIV infection. Pre-steady-state
      kinetics were used to characterize the interaction of EFdA-triphosphate (EFdA-TP)
      with human mitochondrial DNA polymerase gamma (Pol gamma) to assess the potential
      for toxicity. Pol gamma incorporated EFdA-TP 4,300-fold less efficiently than
      dATP, with an excision rate similar to ddATP. This strongly indicates EFdA is a
      poor Pol gamma substrate, suggesting minimal Pol gamma-mediated toxicity,
      although this should be examined under clinical settings.

PMID- 22155824
TI  - High prevalence of isolates with reduced glycopeptide susceptibility in
      persistent or recurrent bloodstream infections due to methicillin-resistant
      Staphylococcus aureus.
AB  - Reduced susceptibility to glycopeptides in methicillin-resistant Staphylococcus
      aureus (MRSA) clinical isolates is considered a risk factor for failure of
      glycopeptide therapy. We compared the prevalences of MRSA isolates with reduced
      glycopeptide susceptibility in patients with versus without persistent or
      recurrent MRSA bloodstream infections. A retrospective cohort study at the
      University Hospital of Geneva identified 27 patients with persistent or recurrent
      clonally related MRSA bacteremic episodes over an 8-year period, which included
      208 consecutive nosocomial MRSA bacteremic episodes. Vancomycin and teicoplanin
      MICs were determined by a modified macrodilution assay allowing improved
      detection of glycopeptide-intermediate MRSA isolates (GISA), characterized by
      elevated teicoplanin or/and vancomycin MICs (>= 4 MUg/ml). For 16 patients (59%),
      their pretherapy and/or posttherapy MRSA isolates showed elevated teicoplanin
      MICs, among which 10 (37%) concomitantly displayed elevated vancomycin MICs. In
      contrast, 11 other patients (41%) were persistently or recurrently infected with
      non-GISA isolates. In comparison, only 39 (22%) of 181 single isolates from
      patients with no microbiological evidence of persistent or recurrent infections
      showed elevated teicoplanin MICs, among which 14 (8%) concomitantly displayed
      elevated vancomycin MICs. Clinical, microbiological, and pharmacokinetic
      variables for patients persistently or recurrently infected with GISA or non-GISA
      isolates were similar. Bacteremic patients with a poor response to glycopeptide
      therapy had a 2.8-fold- and 4.8-fold-higher rates of MRSA isolates displaying
      elevated teicoplanin and vancomycin MICs, respectively, than patients with single
      isolates (P < 0.0001). Detection of elevated teicoplanin MICs may help to predict
      a poor response to glycopeptide therapy in MRSA bacteremic patients.

PMID- 22155825
TI  - Evolution of an incompatibility group IncA/C plasmid harboring blaCMY-16 and
      qnrA6 genes and its transfer through three clones of Providencia stuartii during
      a two-year outbreak in a Tunisian burn unit.
AB  - During a 2-year period in 2005 and 2006, 64 multidrug-resistant Providencia
      stuartii isolates, including 58 strains from 58 patients and 6 strains obtained
      from the same tracheal aspirator, were collected in a burn unit of a Tunisian
      hospital. They divided into four antibiotypes (ATB1 to ATB4) and three SmaI
      pulsotypes (PsA to PsC), including 49 strains belonging to clone PsA (48 of ATB1
      and 1 of ATB4), 11 strains to clone PsB (7 of ATB2 and 4 of ATB3), and 4 strains
      to clone PsC (ATB3). All strains, except for the PsA/ATB4 isolate, were highly
      resistant to broad-spectrum cephalosporins due to the production of the plasmid
      mediated CMY-16 beta-lactamase. In addition, the 15 strains of ATB2 and ATB3
      exhibited decreased quinolone susceptibility associated with QnrA6. Most strains
      (ATB1 and ATB3) were gentamicin resistant, related to an AAC(6')-Ib' enzyme. All
      these genes were located on a conjugative plasmid belonging to the
      incompatibility group IncA/C(2) of 195, 175, or 100 kb. Despite differences in
      size and in number of resistance determinants, they derived from the same
      plasmid, as demonstrated by similar profiles in plasmid restriction analysis and
      strictly homologous sequences of repAIncA/C(2), unusual antibiotic resistance
      genes (e.g., aphA-6), and their genetic environments. Further investigation
      suggested that deletions, acquisition of the ISCR1 insertion sequence, and
      integron cassette mobility accounted for these variations. Thus, this outbreak
      was due to both the spread of three clonal strains and the dissemination of a
      single IncA/C(2) plasmid which underwent a remarkable evolution during the
      epidemic period.

PMID- 22155826
TI  - Resuscitation-promoting factors are required for beta-lactam tolerance and the
      permeability barrier in Mycobacterium tuberculosis.
AB  - Mycobacterial resuscitation-promoting factors (RPFs) have been of great interest
      since the discovery that they promote the growth of nonculturable Mycobacterium
      tuberculosis cells. Yet, their precise role in mycobacterial survival and
      infection has remained elusive. We performed a chemical screen to identify
      molecules that show preferential killing of a Mycobacterium tuberculosis mutant
      lacking RPFs over wild-type bacilli and found that the mutant has enhanced
      sensitivity to the beta-lactam class of antibiotics. By monitoring beta-lactam
      diffusion across the mycobacterial outer membrane, we found that the RPFs are
      required to maintain the outer membrane integrity, as their deletion results in
      an increase in outer membrane permeability.

PMID- 22155827
TI  - Oseltamivir inhibits H7 influenza virus replication in mice inoculated by the
      ocular route.
AB  - The majority of human infections associated with H7 influenza viruses have
      resulted in ocular and not respiratory disease. While oseltamivir has been
      prescribed to individuals presenting with conjunctivitis following H7 virus
      exposure, it is unknown if oseltamivir inhibits virus replication in ocular
      tissue. We demonstrate that H7 viruses possess sensitivity to neuraminidase
      inhibitors and that administration of oseltamivir before ocular virus challenge
      in mice inhibits H7N7 and H7N3 virus replication in ocular and respiratory
      tissues.

PMID- 22155828
TI  - A novel carbon monoxide-releasing molecule fully protects mice from severe
      malaria.
AB  - Severe forms of malaria infection, such as cerebral malaria (CM) and acute lung
      injury (ALI), are mainly caused by the apicomplexan parasite Plasmodium
      falciparum. Primary therapy with quinine or artemisinin derivatives is generally
      effective in controlling P. falciparum parasitemia, but mortality from CM and
      other forms of severe malaria remains unacceptably high. Herein, we report the
      design and synthesis of a novel carbon monoxide-releasing molecule (CO-RM;
      ALF492) that fully protects mice against experimental CM (ECM) and ALI. ALF492
      enables controlled CO delivery in vivo without affecting oxygen transport by
      hemoglobin, the major limitation in CO inhalation therapy. The protective effect
      is CO dependent and induces the expression of heme oxygenase-1, which contributes
      to the observed protection. Importantly, when used in combination with the
      antimalarial drug artesunate, ALF492 is an effective adjunctive and adjuvant
      treatment for ECM, conferring protection after the onset of severe disease. This
      study paves the way for the potential use of CO-RMs, such as ALF492, as
      adjunctive/adjuvant treatment in severe forms of malaria infection.

PMID- 22155829
TI  - Identification of a Cryptococcus neoformans cytochrome P450 lanosterol 14alpha
      demethylase (Erg11) residue critical for differential susceptibility between
      fluconazole/voriconazole and itraconazole/posaconazole.
AB  - Cryptococcus neoformans strains resistant to azoles due to mutations causing
      alterations in the ERG11 gene, encoding lanosterol 14alpha-demethylase, have
      rarely been reported. In this study, we have characterized a C. neoformans
      serotype A strain that is resistant to high concentrations of fluconazole (FLC).
      This strain, which was isolated from an FLC-treated patient, contained five
      missense mutations in the ERG11 gene compared to the sequence of reference strain
      H99. Molecular manipulations of the ERG11 gene coupled with susceptibility to
      triazole revealed that a single missense mutation resulting in the replacement of
      tyrosine by phenylalanine at amino acid 145 was sufficient to cause the high FLC
      resistance of the strain. Importantly, this newly identified point mutation in
      the ERG11 gene of C. neoformans afforded resistance to voriconazole (VRC) but
      increased susceptibility to itraconazole (ITC) and posaconazole (PSC), which are
      structurally similar to each other but distinct from FLC/VRC. The in vitro
      susceptibility/resistance of the strains with or without the missense mutation
      was reflected in the therapeutic efficacy of FLC versus ITC in the animals
      infected with the strains. This study shows the importance of the Y145F
      alteration of Erg11 in C. neoformans for manifestation of differential
      susceptibility toward different triazoles. It underscores the necessity of in
      vitro susceptibility testing for each FLC-resistant C. neoformans clinical
      isolate against different groups of azoles in order to assist patient management.

PMID- 22155830
TI  - High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France:
      novel penA mosaic allele in a successful international clone causes treatment
      failure.
AB  - Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the
      expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the
      last remaining options for first-line gonorrhea treatment, was isolated in Japan.
      Here, we confirm and characterize a second strain (F89) with high-level cefixime
      and ceftriaxone resistance which was isolated in France and most likely caused a
      treatment failure with cefixime. F89 was examined using six species-confirmatory
      tests, antibiograms (33 antimicrobials), porB sequencing, N. gonorrhoeae
      multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and
      sequencing of known gonococcal resistance determinants (penA, mtrR, penB, ponA,
      and pilQ). F89 was assigned to MLST sequence type 1901 (ST1901) and NG-MAST
      ST1407, which is a successful gonococcal clone that has spread globally. F89 has
      high-level resistance to cefixime (MIC = 4 MUg/ml) and ceftriaxone (MIC = 1 to 2
      MUg/ml) and resistance to most other antimicrobials examined. A novel penA mosaic
      allele (penA-CI), which was penA-XXXIV with an additional A501P alteration in
      penicillin-binding protein 2, was the primary determinant for high-level ESC
      resistance, as determined by transformation into a set of recipient strains. N.
      gonorrhoeae appears to be emerging as a superbug, and in certain circumstances
      and settings, gonorrhea may become untreatable. Investigations of the biological
      fitness and enhanced understanding and monitoring of the ESC-resistant clones and
      their international transmission are required. Enhanced disease control
      activities, antimicrobial resistance control and surveillance worldwide, and
      public health response plans for global (and national) perspectives are also
      crucial. Nevertheless, new treatment strategies and/or drugs and, ideally, a
      vaccine are essential to develop for efficacious gonorrhea management.

PMID- 22155831
TI  - Contrasting effects of physical wear on elution of two antibiotics from
      orthopedic cement.
AB  - The use of antibiotics as a supplement to bone cement for the purposes of
      providing a local release of antibiotics is common practice in arthroplasty
      surgery and the kinetics of elution of the antibiotics in such systems have been
      investigated previously. However, in these previous studies no account was taken
      of the potential effects that wear may have on the elution kinetics of the
      antibiotic. Here, we have modified an existing wear testing rig to allow the
      simultaneous study of the elution kinetics of bone cement samples containing
      antibiotics being subjected to immersion only and immersion and conjoint wear.
      The results show contrasting effects with two commonly used antibiotics. Bone
      cement containing daptomycin showed no substantial change in antibiotic elution
      due to wear, while cement containing gentamicin (the most commonly used
      antibiotic in this application) in contrast demonstrated a substantial reduction
      in the rate of antibiotic elution when wear was applied. Scanning electron
      microscopy revealed a possible explanation for these diverse results, due to wear
      induced "sealing" of the surface in conjunction with the crystal morphology of
      the antibiotic.

PMID- 22155832
TI  - Prospective multicenter study of the impact of carbapenem resistance on mortality
      in Pseudomonas aeruginosa bloodstream infections.
AB  - The impact of antimicrobial resistance on clinical outcomes is the subject of
      ongoing investigations, although uncertainty remains about its contribution to
      mortality. We investigated the impact of carbapenem resistance on mortality in
      Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching
      hospitals) observational study of patients with monomicrobial bacteremia followed
      up for 30 days after the onset of bacteremia. The adjusted influence of
      carbapenem resistance on mortality was studied by using Cox regression analysis.
      Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa
      (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa
      (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was
      2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8).
      The regression demonstrated a time-dependent effect of carbapenem resistance on
      mortality as well as a significant interaction with the Charlson index: the
      deleterious effect of carbapenem resistance on mortality decreased with higher
      Charlson index scores. The impact of resistance on mortality was statistically
      significant only from the fifth day after the onset of the bacteremia, reaching
      its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day
      30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at
      day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between
      carbapenem resistance and mortality in patients with P. aeruginosa bacteremia.
      Although resistance was associated with a higher risk of mortality, the study
      suggested that this deleterious effect may not be as great during the first days
      of the bacteremia or in the presence of comorbidities.

PMID- 22155833
TI  - Antibacterial activity of sphingoid bases and fatty acids against Gram-positive
      and Gram-negative bacteria.
AB  - There is growing evidence that the role of lipids in innate immunity is more
      important than previously realized. How lipids interact with bacteria to achieve
      a level of protection, however, is still poorly understood. To begin to address
      the mechanisms of antibacterial activity, we determined MICs and minimum
      bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity-
      the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and
      the fatty acids sapienic acid and lauric acid--against four Gram-negative
      bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these
      values showed differences among lipid treatments (P < 0.0001) for each bacterial
      species except Serratia marcescens and Pseudomonas aeruginosa. D-sphingosine (MBC
      range, 0.3 to 19.6 MUg/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 MUg/ml),
      and phytosphingosine (MBC range, 3.3 to 62.5 MUg/ml) were active against all
      bacteria except S. marcescens and P. aeruginosa (MBC > 500 MUg/ml). Sapienic acid
      (MBC range, 31.3 to 375.0 MUg/ml) was active against Streptococcus sanguinis,
      Streptococcus mitis, and Fusobacterium nucleatum but not active against
      Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa,
      Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium
      (MBC > 500 MUg/ml). Lauric acid (MBC range, 6.8 to 375.0 MUg/ml) was active
      against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500
      MUg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took
      as long as 24 h for others. Hence, sphingoid bases and fatty acids have different
      antibacterial activities and may have potential for prophylactic or therapeutic
      intervention in infection.

PMID- 22155834
TI  - Frequentist and Bayesian pharmacometric-based approaches to facilitate critically
      needed new antibiotic development: overcoming lies, damn lies, and statistics.
AB  - Antimicrobial drug development has greatly diminished due to regulatory
      uncertainty about the magnitude of the antibiotic treatment effect. Herein we
      evaluate the utility of pharmacometric-based analyses for determining the
      magnitude of the treatment effect. Frequentist and Bayesian pharmacometric-based
      logistic regression analyses were conducted by using data from a phase 3 clinical
      trial of tigecycline-treated patients with hospital-acquired pneumonia (HAP) to
      evaluate relationships between the probability of microbiological or clinical
      success and the free-drug area under the concentration-time curve from time zero
      to 24 h (AUC(0-24))/MIC ratio. By using both the frequentist and Bayesian
      approaches, the magnitude of the treatment effect was determined using three
      different methods based on the probability of success at free-drug AUC(0-24)/MIC
      ratios of 0.01 and 25. Differences in point estimates of the treatment effect for
      microbiological response (method 1) were larger using the frequentist approach
      than using the Bayesian approach (Bayesian estimate, 0.395; frequentist estimate,
      0.637). However, the Bayesian credible intervals were tighter than the
      frequentist confidence intervals, demonstrating increased certainty with the
      former approach. The treatment effect determined by taking the difference in the
      probabilities of success between the upper limit of a 95% interval for the
      minimal exposure and the lower limit of a 95% interval at the maximal exposure
      (method 2) was greater for the Bayesian analysis (Bayesian estimate, 0.074;
      frequentist estimate, 0.004). After utilizing bootstrapping to determine the
      lower 95% bounds for the treatment effect (method 3), treatment effect estimates
      were still higher for the Bayesian analysis (Bayesian estimate, 0.301;
      frequentist estimate, 0.166). These results demonstrate the utility of
      frequentist and Bayesian pharmacometric-based analyses for the determination of
      the treatment effect using contemporary trial endpoints. Additionally, as
      demonstrated by using pharmacokinetic-pharmacodynamic data, the magnitude of the
      treatment effect for patients with HAP is large.

PMID- 22155835
TI  - Pharmacodynamics of TD-1792, a novel glycopeptide-cephalosporin heterodimer
      antibiotic used against Gram-positive bacteria, in a neutropenic murine thigh
      model.
AB  - TD-1792 is a novel glycopeptide-cephalosporin heterodimer investigational
      antibiotic that displays potent bactericidal effects against clinically relevant
      Gram-positive organisms in vitro. The present studies evaluated the in vivo
      pharmacokinetics (PK) and pharmacodynamics (PD) of TD-1792 in the neutropenic
      murine thigh infection animal model. TD-1792, dosed subcutaneously (SC), produced
      dose-dependent reduction in the thigh bacterial burden of several organisms,
      including methicillin-susceptible and -resistant strains of Staphylococcus aureus
      and Staphylococcus epidermidis (MSSA, MRSA, MSSE, MRSE, respectively), penicillin
      susceptible strains of Streptococcus pneumoniae (PSSP), Streptococcus pyogenes,
      and vancomycin-intermediate-susceptible Staphylococcus aureus (VISA). In single
      dose efficacy studies, the 1-log(10) CFU kill effective dose (ED(1-log kill))
      estimates for TD-1792 ranged from 0.049 to 2.55 mg/kg of body weight administered
      SC, and the bacterial burden was reduced by up to 3 log(10) CFU/g from
      pretreatment values. Against S. aureus ATCC 33591 (MRSA), the total 24-h log(10)
      stasis dose (ED(stasis)) and ED(1-logkill) doses for TD-1792 were 0.53 and 1.11
      mg/kg/24 h, respectively, compared to 23.4 and 54.6 mg/kg/24 h for vancomycin,
      indicating that TD-1762 is 44- to 49-fold more potent than vancomycin. PK-PD
      analysis of data from single-dose and dose-fractionation studies for MRSA (ATCC
      33591) demonstrated that the total-drug 24-h area under the concentration-time
      curve-to-MIC ratio (AUC/MIC ratio) was the best predictor of efficacy (r(2) =
      0.826) compared to total-drug maximum plasma concentration of drug-to-MIC ratio
      (Cmax/MIC ratio; r(2) = 0.715) and percent time that the total-drug plasma drug
      concentration remains above the MIC (%Time>MIC; r(2) = 0.749). The magnitudes of
      the total-drug AUC/MIC ratios associated with net bacterial stasis, a 1-log(10)
      CFU reduction from baseline and near maximal effect, were 21.1, 37.2, and 51.8,
      respectively. PK-PD targets based on such data represent useful inputs for
      analyses to support dose selection decisions for clinical studies of patients.

PMID- 22155836
TI  - Molecular identification of extended-spectrum-beta-lactamase genes from
      Enterobacteriaceae isolated from healthy human carriers in Switzerland.
AB  - In this study, fecal samples from 586 healthy humans were investigated to
      determine the occurrence of extended-spectrum-beta-lactamase (ESBL)-producing
      Enterobacteriaceae in Swiss people. A total of 5.8% of the human fecal samples
      yielded ESBL producers, and all of the 34 isolated strains were Escherichia coli.
      PCR analysis revealed that 14 strains produced CTX-M-15, 10 produced CTX-M-1, 7
      strains produced CTX-M-14, and 2 strains produced CTX-M-2 ESBLs. One strain
      produced SHV-12 ESBL. Of the 34 isolates, 15 produced additional TEM-1 broad
      spectrum beta-lactamases. By serotyping, a high degree of diversity among the
      strains was found.

PMID- 22155837
TI  - Pharmacodynamic analysis of a serine protease inhibitor, MK-4519, against
      hepatitis C virus using a novel in vitro pharmacodynamic system.
AB  - The development of new antiviral compounds active against hepatitis C virus (HCV)
      has surged in recent years. In order for these new compounds to be efficacious in
      humans, optimal dosage regimens for each compound must be elucidated. We have
      developed a novel in vitro pharmacokinetic/pharmacodynamic system, the BelloCell
      system, to identify optimal dosage regimens for anti-HCV compounds. In these
      experiments, genotype 1b HCV replicon-bearing cells (2209-23 cells) were
      inoculated onto carrier flakes in BelloCell bottles and treated with MK-4519, a
      serine protease inhibitor. Our dose-ranging studies illustrated that MK-4519
      inhibited replicon replication in a dose-dependent manner, yielding a 50%
      effective concentration (EC(50)) of 1.8 nM. Dose-fractionation studies showed
      that shorter dosing intervals resulted in greater replicon suppression,
      indicating that the time that the concentration is greater than the EC(50) is the
      pharmacodynamic parameter for MK-4519 linked with inhibition of replicon
      replication. Mutations associated with resistance to serine protease inhibitors
      were detected in replicons harvested from all treatment arms. These data suggest
      that MK-4519 is highly active against genotype 1b HCV, but monotherapy is not
      sufficient to prevent the amplification of resistant replicons. In summary, our
      findings show that the BelloCell system is a useful and clinically relevant tool
      for predicting optimal dosage regimens for anti-HCV compounds.

PMID- 22155838
TI  - Novel potent metallocenes against liver stage malaria.
AB  - Novel conjugates of the antimalarial drug primaquine (compound 1) with ferrocene,
      named primacenes, have been synthesized and screened for their activities against
      blood stage and liver stage malaria in vitro and host-vector transmission in
      vivo. Both transmission-blocking and blood-schizontocidal activities of the
      parent drug were conserved only in primacenes bearing a basic aliphatic amine
      group. Liver stage activity did not require this structural feature, and all
      metallocenes tested were comparable to or better than primaquine in this regard.
      Remarkably, the replacement of primaquine's aliphatic chain by hexylferrocene, as
      in compound 7, led to a ~45-fold-higher level activity against liver stage
      parasitemia than that of primaquine.

PMID- 22155839
TI  - Decrease of antibiotic consumption in children with upper respiratory tract
      infections after implementation of an intervention program in Cyprus.
AB  - To assess the impact of intervention on antibiotic misuse in children, parents'
      and pediatricians' knowledge, attitudes, and practices (KAP) concerning
      antibiotic use were evaluated pre- and postintervention in Larnaca (Cyprus) and
      Limassol (Cyprus). Concurrently, pediatricians documented upper respiratory tract
      infection (URTI) visits and pharmacists provided antibiotic consumption data.
      Intervention was implemented for parents and pediatricians residing in Larnaca.
      The consumption/URTI incidence index was significantly reduced in Larnaca but not
      in Limassol. Parental responses to a KAP questionnaire remained unchanged;
      therefore, antibiotic consumption reduction is attributable to pediatricians'
      education.

PMID- 22155840
TI  - Interactions of antidepressants and ethanol on spontaneous locomotor activity and
      rotarod performance in NMRI and C57BL/6 mice.
AB  - In order to find appropriate doses for studying antidepressant-ethanol
      interaction in two mouse strains, spontaneous locomotor activity and rotarod
      performance were first studied in NMRI mice after amitriptyline 3-30 mg/kg,
      mianserin 3-30 mg/kg, nomifensine 1- 10 mg/kg, citalopram 3-100 mg/kg, and
      ethanol 1-3 g/kg intraperitoneally. Ethanol increased significantly locomotor
      activity at 1 g/kg and impaired rotarod performance at 2 and 3 g/kg.
      Amitriptyline and mianserin decreased dose-dependently locomotor activity at
      doses >= 10 mg/kg. Nomifensine and citalopram increased locomotor activity at 10
      mg/kg and citalopram 100 mg/kg decreased it. Rotarod performance was affected
      only by amitriptyline 10 and 30 mg/kg and citalopram 100 mg/kg, which impaired
      performance. Interaction studies with the two strains using amitriptyline,
      mianserin, nomifensine and citalopram 10 mg/kg and ethanol 1 g/kg showed that
      C57BL/6 mice were less sensitive than NMRI mice to the stimu lating effects of
      ethanol and more sensitive to impairment of rotarod performance by amitrip tyline
      and mianserin. C57BL/6 mice had a significantly poorer baseline performance on
      rotarod, and the citalopram plus ethanol combination impaired their performance
      severely, although drugs alone did not impair this test. The results suggest that
      decreased locomotor activity as a measure of antidepressant-induced sedation does
      not parallel with impaired performance on rotarod and that significant strain
      differences can be seen in psy chopharmacological tests and responses to drugs in
      mice.

PMID- 22155841
TI  - The scopolamine model of dementia: determination of central cholinomimetic
      effects of physostigmine on cognition and biochemical markers in man.
AB  - Administration of the muscarinic antagonist scopolamine has been proposed as a
      pharmacological model for Alzheimer's disease. We have attempted to characterize
      the cognitive deficits produced by the administration of scopolamine (0.2 and 0.4
      mg intra muscularly) to normal volunteers. We have also demonstrated reversal of
      these deficits by the cholinesterase inhibitor physostigmine (1.2 mg
      intramuscularly). Physostigmine also elevated subjects' plasma ACTH levels, a
      marker of central cholinergic activity. In the cognitive study, we found that
      scopolamine impaired subjects' performance on verbal learning, spatial learning
      and choice reaction time. These changes were associated with subjective sedation
      as measured by analogue rating scales. Physostigmine attenuated the impairment in
      verbal learning and reduced subjective sedation. In the biochemical study we
      examined the effects of the same drug regimes on plasma ACTH levels.
      Physostigmine administered with a peripherally active cholinergic antagonist
      (glycopyrrolate 0.2 mg intramuscularly) produced a rise in ACTH level which
      reached a peak 30 min after drug administration. Such a rise was not apparent
      when the physostigmine was coadministered with scopolamine. These results suggest
      that cognitive and neuroendocrine indices of central cholinergic activity such as
      these may be useful in determining the effectiveness of potential new therapeutic
      agents for Alzheimer's disease.

PMID- 22155842
TI  - The discriminative stimulus produced by pentylenetetrazol: effects of systemic
      anxiolytics and anxiogenics, aggressive defeat and midazolam or muscimol infused
      into the amygdala.
AB  - Rats were trained to discriminate the interoceptive stimulus generated by
      systemic administration of pentylenetetrazol. A series of experiments confirmed
      earlier studies that rats generalized to the pentylenetetrazol cue following
      treatment with drugs purported to have anxiogenic properties, such as beta
      carboline carboxylic acid (betaCCM) and FG 7142. The benzodiazepine antagonist,
      Ro 15-1788, did not generalize to the pentylenetetrazol cue. Anxiolytic drugs,
      such as the benzodiazepines chlordiazepoxide and midazolam, prevented
      discrimination of the pentylenetetrazol cue and resulted in generalization to the
      saline vehicle. Ritanserin, a 5-HT(2) receptor antagonist and putative anxiolytic
      compound, did not prevent discrimination of the pentylenetetrazol cue. Subjecting
      the rats to aggressive defeat in a home cage intruder test (following injection
      of saline) resulted in a significant proportion of them generalizing to the
      pentylenetetrazol discriminative stimulus. This result is discussed in terms of
      the suggested anxiogenic nature of the effects of treatment with
      pentylenetetrazol. Infusion of midazolam bilaterally into the amygdala
      antagonized, in a dose-dependent manner, dis crimination of the interoceptive
      stimulus generated by systemic treatment with FG 7142 (which itself generalized
      to the pentylenetetrazol cue). Furthermore, infusion of the GABA agonist,
      muscimol, bilaterally into the amygdala antagonized the pentylenetetrazol discri
      minative stimulus in a dose-dependent manner. These data suggest that amygdaloid
      mech anisms may be involved in the generation or discrimination of the
      distinctive, interoceptive stimuli associated with pentylenetetrazol and the beta
      carboline, FG 7142. The data are discussed in the context of suggested functions
      of the amygdaloid complex in fear-motivated behaviour.

PMID- 22155843
TI  - Serum haloperidol levels and clinical response in chronic, treatment-resistant
      schizophrenic patients.
AB  - Eleven chronic treatment-resistant schizophrenic in-patients were treated with
      haloperidol (HPL) or placebo with a fixed ascending dose schedule for 20 weeks.
      Seven patients relapsed and were withdrawn and five of these re-entered, single
      blind, on known active treatment. Two weekly clinical ratings and weekly serum
      HPL levels were carried out throughout the study. More patients on placebo
      dropped out and at an earlier stage than those on active treatment but the
      difference was not statistically significant. Despite wide individual variations
      in both serum HPL levels and clinical response, these were positively correlated.
      HPL appeared to be of more value in the prevention of relapse than in symptom
      reduction. Overall, the clinical response was poor and a 'therapeutic window'
      could not be demonstrated either for the group as a whole or in any individual
      patient. There was no additional therapeutic benefit in exceeding serum HPL
      levels of 20 ng/ml in any of our patients. Since this serum level was achieved by
      daily doses of 10-40 mg HPL and the relationship between dose and serum level is
      linear, the use of serum HPL estimations is not likely to be of value in the
      routine clinical management of treatment-resistant patients.

PMID- 22155844
TI  - Abstracts from the summer meeting of the british association for
      psychopharmacology, held in cambridge, England 10-13 july 1988. The abstracts are
      arranged in alphabetical order by first author.

PMID- 22155845
TI  - A dominant allele of Arabidopsis pectin-binding wall-associated kinase induces a
      stress response suppressed by MPK6 but not MPK3 mutations.
AB  - The plant cell wall is composed of a matrix of cellulose fibers, flexible pectin
      polymers, and an array of assorted carbohydrates and proteins. The receptor-like
      Wall-Associated Kinases (WAKs) of Arabidopsis bind pectin in the wall, and are
      necessary both for cell expansion during development and for a response to
      pathogens and wounding. Mitogen Activated Protein Kinases (MPKs) form a major
      signaling link between cell surface receptors and both transcriptional and enzyme
      regulation in eukaryotes, and Arabidopsis MPK6 and MPK3 indeed have important
      roles in development and the response to stress and pathogens. A dominant allele
      of WAK2 requires kinase activity and activates a stress response that includes an
      increased ROS accumulation and the up-regulation of numerous genes involved in
      pathogen resistance, wounding, and cell wall biogenesis. This dominant allele
      requires a functional pectin binding and kinase domain, indicating that it is
      engaged in a WAK signaling pathway. A null mutant of the major plasma membrane
      ROS-producing enzyme complex, rbohd/f does not suppress the WAK2cTAP-induced
      phenotype. A mpk6, but not a mpk3, null allele is able to suppress the effects of
      this dominant WAK2 mutation, thus distinguishing MPK3 and MPK6, whose activity
      previously was thought to be redundant. Pectin activation of gene expression is
      abated in a wak2-null, but is tempered by the WAK-dominant allele that induces
      elevated basal stress-related transcript levels. The results suggest a mechanism
      in which changes to the cell wall can lead to a large change in cellular
      responses and help to explain how pathogens and wounding can have general effects
      on growth.

PMID- 22155846
TI  - Out-of-plane growth of CNTs on graphene for supercapacitor applications.
AB  - This paper describes the fabrication and characterization of a hybrid
      nanostructure comprised of carbon nanotubes (CNTs) grown on graphene layers for
      supercapacitor applications. The entire nanostructure (CNTs and graphene) was
      fabricated via atmospheric pressure chemical vapor deposition (APCVD) and
      designed to minimize self-aggregation of the graphene and CNTs. Growth parameters
      of the CNTs were optimized by adjusting the gas flow rates of hydrogen and
      methane to control the simultaneous, competing reactions of carbon formation
      toward CNT growth and hydrogenation which suppresses CNT growth via hydrogen
      etching of carbon. Characterization of the supercapacitor performance of the CNT
      graphene hybrid nanostructure indicated that the average measured capacitance of
      a fabricated graphene-CNT structure was 653.7 MUF cm(-2) at 10 mV s(-1) with a
      standard rectangular cyclic voltammetry curve. Rapid charging-discharging
      characteristics (mV s(-1)) were exhibited with a capacitance of approximately 75%
      (490.3 MUF cm(-2)). These experimental results indicate that this CNT-graphene
      structure has the potential towards three-dimensional (3D) graphene-CNT multi
      stack structures for high-performance supercapacitors.

PMID- 22155847
TI  - Compton profiles and nesting of Fermi surfaces for B2-TiNi and B2-TiPd.
AB  - The band structures of the shape memory alloys B2-TiNi and B2-TiPd are calculated
      by the full potential linearized augmented plane wave method with the local
      density approximation. The theoretical Compton profiles for B2-TiNi and B2-TiPd
      are calculated. In addition, the three-dimensional (3D) occupation number
      densities obtained by Lock-Crisp-West (LCW) analysis are presented for the first
      time. These 3D occupation number densities are in good agreement with the Compton
      scattering experiment for TiNi. Both shape memory alloys are based on martensitic
      transformation, which is caused by soft phonons. The charge-density wave is
      created by nesting of Fermi surfaces, which leads to phonon softening. To examine
      the nesting vectors quantitatively, we calculate the generalized susceptibility
      chi(q). chi(q) shows peaks at 0.315[110]2pi/a and 0.4[111]2pi/a for TiNi and at
      0.275[110]2pi/a and 0.395[111]2pi/a for TiPd. Although the nesting vector in the
      [110] direction agrees with that from the phonon experiment, the nesting vector
      in the [111] direction differs from that in the experimental results.

PMID- 22155848
TI  - Pancreatoduodenectomy with a modified duct-to-mucosa pancreaticojejunostomy: an
      analysis of 101 consecutive patients.
AB  - BACKGROUND/AIMS: The aim of the study was to analyze in-hospital morbidity and
      mortality after pancreatoduodenectomy (PD) with a modified duct-to-mucosa
      pancreaticojejunostomy. METHODOLOGY: We retrospectively analyzed 101 consecutive
      patients who underwent PD at our center between January 2002 and December 2010.
      Two-layered duct-to-mucosa pancreaticojejunostomy was performed over an internal
      transanastomotic stent in all patients. RESULTS: The overall in-hospital
      morbidity and mortality rate was 48% and 6%, respectively. Three patients died as
      a consequence of local complications including mesenteric ischemia in two and
      acute necrotizing pancreatitis in one case. Pancreatic fistula occurred in one
      (1%) patient and was treated conservatively with good outcome. The wound
      infection was the most common surgical complication (20/101; 20%) and occurred
      more often in patients who had a biliary stent inserted endoscopically prior to
      surgery (15/38; 39%), as compared to those without the stent (5/63; 8%;
      p=0.0003). CONCLUSIONS: The results of the present study suggest that a two
      layered duct-to-mucosa pancreaticojejunostomy with internal transanastomotic
      stent is a safe anastomosis, associated with a very low risk of pancreatic
      fistula. The presence of a biliary stent at the time of surgery represents a risk
      factor for the development of postoperative wound infection.

PMID- 22155849
TI  - Comparison of multidetector CT and endoscopic ultrasonography in malignant
      pancreatic mass lesions.
AB  - BACKGROUND/AIMS: Endoscopic ultrasonography (EUS) has been shown to be superior
      to conventional CT in detecting and staging pancreatic cancer. We conducted a
      prospective trial to compare EUS and MDCT, in discriminating benign/malignant, in
      determining local and vascular invasion of a suspected pancreatic cancer and
      deciding its resectability. METHODOLOGY: The study was performed at the
      Gastroenterology Department of Izmir Ataturk Training and Research Hospital, from
      June 2009 to June 2010, all patients with suspected pancreatic and periampullary
      tumors referred to our department were enrolled. A total of 56 patients were
      evaluated at the beginning. Five patients having distal CBD tumor (n=2),
      gallbladder tumor (n=1) and papillary tumor (n=2) were excluded from the study.
      Analysis was done for the remaining 51 patients. RESULTS: For the diagnosis of
      resectability/unresectability, EUS alone demonstrated a definite role in 4 (9%)
      of the 43 patients in confirming surgical and pathologic results and MDCT alone
      demonstrated a definite role in 6 (14%) of the 43 patients in confirming their
      results. An accurate diagnostic decision regarding resectability/unresectability
      was accomplished in 27 (63%) patients with EUS and MDCT. CONCLUSIONS: While MDCT
      is clinically quite effective, in terms of a correct
      resectability/unresectability decision, EUS should also be used.

PMID- 22155850
TI  - Prediction of a side effect and efficacy of adjuvant chemotherapy with
      gemcitabine for post operative patient of pancreatic cancer by a genetic
      polymorphism analysis.
AB  - BACKGROUND/AIMS: Single nucleotide polymorphism (SNP) of the genes for ATP
      binding cassette transporters is related to the side effects of anticancer drugs
      and that of drug metabolism-related enzyme genes is involved in the activation of
      gemcitabine (GEM). METHODOLOGY: Forty eight patients treated with adjuvant GEM
      chemotherapy after pancreatic cancer resection was examined for the SNP of
      multidrug-resistance 1 (MDR1) 2677, MDR1 3435, breast cancer resistance protein
      (BCRP) 421, ribonucleotide reductase M1 (RRM1)(-)524, RRM1(-)37 and deoxycytidine
      deaminase (CDA) 208. We divided the patients according to normal group: patients
      homozygous for a wild-type allele or heterozygous for a mutant allele and mutant
      group: those homozygous for a mutant allele. Both groups were compared regarding
      the outcome and the occurrence and severity of side effects. RESULTS: MDR1 2677,
      MDR1 3435, BCRP421, RRM1(-) 524, RRM1(-) 37 and CDA mutant groups comprised 37.5,
      31.3, 0, 12.5, 4.2 and 4.2%, respectively. The occurrence of >G3 side effects was
      the most frequent in the MDR1 2677 mutant group at 39%. The disease-free survival
      and overall survival tended to be longer in the MDR1 2677 mutant group.
      CONCLUSIONS: A correlation between the SNP of MDR1 2677 and drug response in
      patients receiving GEM chemotherapy.

PMID- 22155851
TI  - Total pancreatectomy with en bloc celiac axis resection for a pancreatic
      adenocarcinoma involving both the gastroduodenal artery and the celiac artery.
AB  - A pancreatic adenocarcinoma involving both the celiac artery and the
      gastroduodenal artery is often considered to be unresectable because the
      simultaneous division of both arteries may result in an acute severe ischemia of
      the liver and the stomach. We report here a case of total pancreatectomy with en
      bloc celiac axis resection for a 61-year-old female with a pancreatic
      adenocarcinoma involving both the celiac artery and the gastroduodenal artery.
      The patient had a replaced right hepatic artery from the superior mesenteric
      artery and a replaced left hepatic artery from the left gastric artery, which was
      directly arising from the aorta. Preserving these collateral arteries, neither
      hepatic artery reconstruction nor total gastrectomy was needed after resection.
      The reported incidence of similar arterial anatomy was only 0.2% but the precise
      evaluation of arterial anatomy is important to offer a chance of curative
      resection for patients with usually unresectable locally advanced pancreatic
      cancer.

PMID- 22155852
TI  - Immunophenotypic profile of intrahepatic and circulating lymphocytes in chronic
      hepatitis B patients.
AB  - BACKGROUND/AIMS: Persistent hepatitis B virus (HBV) infection is associated with
      particular deficiencies in the host immune system. To gain insight into the role
      of lymphocyte subsets involved in viral clearance and hepatic injury.
      METHODOLOGY: The immunophenotype of peripheral blood and biopsied liver tissues
      in hepatitis B patients were examined. RESULTS: Among lymphocyte subsets
      analyzed, CD45RA+CD62L+ subsets were significantly lower in HBV-infected livers
      than in healthy controls. Intrahepatic naive lymphocytes was negatively
      correlated with serum viral load (r =-0.47, p<0.05) and liver injury measured by
      serum alanine aminotransferase (ALT) (r=-0.36, p<0.05). Serum HBV DNA was also
      negatively associated with intrahepatic CD8+CD95+ (r=-0.49, p<0.01), circulating
      CD4+HLA-DR+ (r=-0.43, p<0.05) and circulating CD3+CD(16+56)+ (r =-0.35, p<0.05).
      CD3+CD8+ subsets were positively correlated with serum ALT and HBV DNA (r=0.56,
      0.74, p<0.01), respectively. CONCLUSIONS: These data suggest a key role for the
      exhaustion of intrahepatic naive lymphocyte reservoir in the development of a
      weak antiviral immune response and the inability to control viral replication in
      chronic hepatitis B patients. While cellular immunity is critical to clear the
      viral load, over-activated cytotoxic lymphocytes may also be involved in hepatic
      injury.

PMID- 22155853
TI  - Non-alcoholic fatty liver disease adversely affects the glycemic control afforded
      by sitagliptin.
AB  - BACKGROUND/AIMS: Recently, high serum DPP-4 activity was found in patients with
      NAFLD. Therefore, the possibility of NAFLD adversely influencing the therapeutic
      effect afforded by DPP-4 inhibitors in type 2 diabetic patients was suggested.
      METHODOLOGY: A total of 20 type 2 DM patients with NAFLD and 85 type 2 DM
      patients without NAFLD were enrolled in the present study. The patients were
      administered sitagliptin at the dose of 50 mg/day for 12 weeks. RESULTS: The
      change in HbA1c from the baseline following treatment with sitagliptin was -0.47%
      (4 weeks), -0.73% (8 weeks) and -0.88% (12 weeks) in the type 2 DM patients with
      NAFLD and -0.26% (4 weeks), -0.41% (8 weeks) and -0.49% (12 weeks) in type 2 DM
      without NAFLD. The changes in the HbA1c from the baseline after sitagliptin
      treatment for 8 and 12 weeks were significantly greater in type 2 DM patients
      with NAFLD than in type 2 DM patients without NAFLD. CONCLUSIONS: The results of
      this study suggest that NAFLD might adversely affect the therapeutic effect
      afforded by sitagliptin treatment in patients with type 2 DM. NAFLD may be an
      independent predictor of the effect of sitagliptin in patients with type 2 DM.

PMID- 22155854
TI  - Biliary variations and biliary complications in living donor liver
      transplantation.
AB  - BACKGROUND/AIMS: To evaluate the relationship between biliary complications of
      recipients and biliary variations of donors in living donor liver
      transplantation. METHODOLOGY: From January 2008 to February 2011, 60 adult
      patients underwent LDLT at West China Hospital, Sichuan University, China. After
      cholecystectomy, an intraoperative cholangiogram was routinely performed through
      the cystic duct to identify biliary anatomy. The recipients have been followed up
      for 3 to 40 months. RESULTS: Biliary complications developed in 9 patients
      (15.0%) and 3 (5.0%) were diagnosed as anastomotic leakage, while 6 (10.0%)
      developed strictures. The incidence of biliary variations was 26%. There was no
      statistical difference in biliary complications no matter the biliary variations.
      CONCLUSIONS: Performing biliary variations assessment may contribute to reduction
      of biliary complications.

PMID- 22155855
TI  - Manometric perfusion test in biliary strictures treatment.
AB  - BACKGROUND/AIMS: To assess the biliary manometric perfusion test (BMPT) for
      evaluating success in treating benign biliary strictures. METHODOLOGY: During
      2003 to 2010, 29 patients were subjected to BMPT after percutaneous balloon
      dilatation treatment. Intrabiliary pressure less than 20cm of water was
      considered the success threshold. Results of BMPT evaluation were retrospectively
      compared with a similar group where the standard clinical test was used for
      evaluating treatment success. The clinical test group included 21 patients
      treated for biliary strictures from 1994 to 2006. RESULTS: The two groups were
      statistically similar by age and gender. The BMPT group was tested without
      complications and pressure inside the biliary tree was less than 20cm of water in
      27 of 29 patients. Subsequently, catheters were removed from all 27. Three
      patients required re-interventions 13 days, 11 months and 32 months later. Kaplan
      Meier survival analysis showed that the probability of biliary patency at 3 year
      was 82.2%. There was no significant difference between groups by this measure
      (log rank test, p=0.624). CONCLUSIONS: The manometric test is an alternative for
      evaluating success in treating benign biliary strictures. It is simple, less time
      consuming, economical, safe, effective and more comfortable for patients than the
      clinical test.

PMID- 22155856
TI  - Preoperative radiotherapy combined with S-1 for advanced lower rectal cancer:
      phase I trial.
AB  - BACKGROUND/AIMS: S-1 based chemoradiation is the recommended treatment for rectal
      cancer; however, the optimal scheduling and dosing are not yet established. A
      Phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1
      with radiotherapy (RT). Endpoints were the toxicity profile of this regimen and
      to determine the recommended dose (RD). METHODOLOGY: Conformal RT was given using
      4 fields at daily fractions of 2Gy on 5 days per week to a total dose of 40Gy.
      Concurrently S-1 was given twice daily throughout RT. Eligible patients had a
      newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within
      12cm of the anal verge suitable for curative resection. Surgery was performed 6
      weeks from completion of preoperative chemoradiotherapy. The dose escalating from
      S-1 80mg/m2/day (Level 1) to 100mg/m2/day (Level 2). RESULTS: Nine patients were
      valid for safety. In all patients, S-1 was administered. There was no dose
      limiting toxicity (DLT) in patients treated at dose Level 1. Six patients were
      enrolled in the dose-escalation phase. At dose Level 2, two patients developed
      DLT and this was considered the MTD. Objective response according to RECIST were
      observed in 5 of 9 patients who had measurable disease (56%). CONCLUSIONS: The RD
      of S-1 with concurrent RT was determined to be 80mg/m2/day. Preoperative RT
      combined with S-1 was feasible and well tolerated.

PMID- 22155857
TI  - Creatinine clearance rate and nerve conduction velocity are effective in
      objectively assessing oxaliplatin-neuropathy in patients with colorectal
      carcinoma.
AB  - BACKGROUND/AIMS: To evaluate the efficacy of using creatinine clearance rate
      (CCr) and nerve conduction velocity (NCV) study in objectively assessing
      oxaliplatin-induced neuropathy, a study was performed. METHODOLOGY: Sixty-eight
      patients with unresectable metastatic colorectal carcinoma were enrolled. FOLFOX
      4 regimen was administrated as first-line chemotherapy. Patients were divided
      into CCr-impaired (60-80mL/min) and CCr-fair (>80mL/min) groups before treatment.
      NCV was examined accordingly, and the correlations of CCr and NCV with
      oxaliplatin-induced neuropathy were analyzed. RESULTS: An excellent correlation
      was identified in impaired CCr and the severity of neurological symptoms
      (p<0.01). Nine (47.3%) CCr-impaired patients developed severe (grade 3 or 4)
      neuropathy and only 5 (10.2%) CCr-fair patients developed grade 3/4 neuropathy. A
      good correlation was found in NCV abnormalities and the severity of neuropathy,
      too (p<0.01). Thirteen (33.3%) patients with impaired NCV developed grade 3/4
      neuropathy but only one (3.4%) patient with normal NCV had grade 3/4 neuropathy.
      However, there remained 26 (66.7%) NCV-impaired patients who had no or only mild
      neurological symptoms. CONCLUSIONS: These data suggest that CCr and NCV correlate
      well with the severity of neurological symptoms in colorectal cancer patients
      treated with oxaliplatin-based chemotherapy. The additions of CCr and NCV, to a
      precise physical examination, are helpful in objectively assessing oxaliplatin
      induced neuropathy.

PMID- 22155858
TI  - Is serum placental growth factor a prognostic marker for stage III colorectal
      cancer patients?
AB  - BACKGROUND/AIMS: To evaluate the clinical usefulness of serum placental growth
      factor (sPIGF) levels in stage III colorectal adenocarcinomas (CRC). METHODOLOGY:
      Serum PIGF were measured in 70 healthy controls and in 80 stage III CRC patients.
      Also the association between preoperative sPGF levels, clinicopathological
      features and patients survival were evaluated in stage III CRC patients. RESULTS:
      sPIGF levels in stage III CRC patients were significantly higher than those in
      controls. There was no significant association between sPIGF levels and
      clinicopathological features and sPIGF is not a prognostic factor for survival.
      Multivariate regression analysis showed the sPIGF levels (hazard ratio=3.28; 95%
      CI=1.10-9.5, p=0.032) to be significant independent factors for local recurrence.
      CONCLUSIONS: Serum PIGF levels in stage III CRC patients are significantly higher
      compared with normal controls and may be an indicator of local recurrence in
      stage III CRC patients.

PMID- 22155859
TI  - Oncological outcome of laparoscopic surgery for advanced colon cancer: a
      community hospital's experience.
AB  - BACKGROUND/AIMS: Similar oncological outcomes of laparoscopic and open surgery
      for advanced colon cancer have been reported by several large-scale studies.
      Whether those results are applicable to community hospitals is questionable.
      METHODOLOGY: From January 2007 to December 2010, 95 patients with colon cancer
      underwent laparoscopic surgery at Seirei Mikatahara General Hospital. Of these,
      40 patients with pathological stage II/III colon cancer were subjected to this
      retrospective analysis (laparoscopic resection (LAP) group). Their outcomes were
      compared with those of 58 patients with pathological stage II/III colon cancer
      who underwent open surgery between January 2005 and December 2006 (open resection
      (OP) group). RESULTS: Surgical complications were significantly less frequent in
      the LAP group than in the OP group. Three-year disease-free survival (DFS) and
      overall survival (OS) for stage II colon cancer were 88.9% and 100% in the LAP
      group, and 90% and 86.7% in the OP group (p=0.976 and p=0.285), respectively.
      Three-year DFS and OS for stage III colon cancer were 85.4% and 86.9% in the LAP
      group, and 75.3% and 83.8% in the OP group (p=0.613 and p=0.837), respectively.
      CONCLUSIONS: Laparoscopic surgery for advanced colon cancer seems feasible and
      the oncological outcome is adequate in a community hospital setting.

PMID- 22155860
TI  - A novel screening biomarker in gastric cancer: serum Dickkopf-1.
AB  - BACKGROUND/AIMS: Despite all the knowledge about gastric cancer, there is no
      prognostic biomarker which could be useful for early detection. Dickkopf-1 (DKK
      1), a secreted protein, is known as a negative regulator of the Wnt signaling
      pathway. DKK-1 is reported to be over expressed in many malignant tissues. The
      purpose of this study was to elucidate the normal level of serum DKK-1 (sDKK-1)
      levels in healthy Turkish peoples and to investigate the clinical utility of sDKK
      1 levels for gastric cancer screening. METHODOLOGY: Serum DKK-1 levels were
      measured in 69 healthy controls and in 60 gastric adenocarcinoma patients with
      ELISA and sDKK-1 levels were compared with clinicopathological features and
      outcomes in gastric cancer patients. RESULTS: Serum concentrations of DKK-1 in
      gastric adeno cancer patients were significantly higher than control patients
      (p<0.001). The optimal cut-off for sDKK-1 levels order to discriminate control
      group from gastric cancer patients was 25U/mL with sensitivity equal to 100% and
      specificity equal to 100%. CONCLUSIONS: Serum DKK-1 levels may be a potentially
      useful novel serologic marker for gastric cancers.

PMID- 22155861
TI  - Presence of free cancer cells in the peritoneal cavity of patients who underwent
      curative gastrectomy with lymph node dissection.
AB  - BACKGROUND/AIMS: The aim of this study was to determine the ratio of patients
      with positive peritoneal cytology who underwent radical gastrectomy for gastric
      cancer, to evaluate the factors effecting risk of positive cytology and to
      analyze the effects cytology findings on survival. METHODOLOGY: Peritoneal lavage
      samples were obtained from 255 patients who underwent radical gastrectomy with D2
      (184 patients) or D3 (71 patients) lymph node dissection between January 2000 and
      December 2007. RESULTS: Thirty-six (14.1%) of 255 patients had free cancer cells
      in the wash cytology samples. T stage (T4) and differentiation were found to be
      independent risk factors for positive peritoneal cytology in multivariate
      analysis. Survival rate of cytology negative patients was significantly higher,
      however cytology findings were not found to be an independent prognostic factor
      for survival. T stage, lymph node metastasis and Borrmann classification
      (Borrmann type 4) appeared to be independent prognostic factors for survival in
      multivariate analyses. CONCLUSIONS: Peritoneal cytology does not provide
      additional information according to the TNM (1997) staging system. However, it
      should be employed intraoperatively before potentially curable serosa involved
      gastric carcinomas, especially for T4 tumors. Surgery alone will not be enough
      for patients with positive cytology and further therapies should be employed.

PMID- 22155862
TI  - Computing graphlet signatures of network nodes and motifs in Cytoscape with
      GraphletCounter.
AB  - Biological network analysis can be enhanced by examining the connections between
      nodes and the rest of the network. For this purpose we have developed
      GraphletCounter, an open-source software tool for computing graphlet degree
      signatures that can operate on its own or as a plug-in to the network analysis
      environment Cytoscape. A unique characteristic of GraphletCounter is its ability
      to compute the graphlet signatures of network motifs, which can be specified by
      files generated by the motif-finding tool mfinder. GraphletCounter displays
      graphlet signatures for visual inspection within Cytoscape, and can output
      graphlet data for integration with larger workflows. AVAILABILITY AND
      IMPLEMENTATION: GraphletCounter is implemented in Java. It can be downloaded from
      the Cytoscape plugin repository, and is also available at
      http://sonmezsysbio.org/software/ graphletcounter.

PMID- 22155863
TI  - BPDA2d--a 2D global optimization-based Bayesian peptide detection algorithm for
      liquid chromatograph-mass spectrometry.
AB  - MOTIVATION: Peptide detection is a crucial step in mass spectrometry (MS) based
      proteomics. Most existing algorithms are based upon greedy isotope template
      matching and thus may be prone to error propagation and ineffective to detect
      overlapping peptides. In addition, existing algorithms usually work at different
      charge states separately, isolating useful information that can be drawn from
      other charge states, which may lead to poor detection of low abundance peptides.
      RESULTS: BPDA2d models spectra as a mixture of candidate peptide signals and
      systematically evaluates all possible combinations of possible peptide candidates
      to interpret the given spectra. For each candidate, BPDA2d takes into account its
      elution profile, charge state distribution and isotope pattern, and it combines
      all evidence to infer the candidate's signal and existence probability. By
      piecing all evidence together--especially by deriving information across charge
      states--low abundance peptides can be better identified and peptide detection
      rates can be improved. Instead of local template matching, BPDA2d performs global
      optimization for all candidates and systematically optimizes their signals. Since
      BPDA2d looks for the optimal among all possible interpretations of the given
      spectra, it has the capability in handling complex spectra where features
      overlap. BPDA2d estimates the posterior existence probability of detected
      peptides, which can be directly used for probability-based evaluation in
      subsequent processing steps. Our experiments indicate that BPDA2d outperforms
      state-of-the-art detection methods on both simulated data and real liquid
      chromatography-mass spectrometry data, according to sensitivity and detection
      accuracy. AVAILABILITY: The BPDA2d software package is available at
      http://gsp.tamu.edu/Publications/supplementary/sun11a/.

PMID- 22155864
TI  - A simple statistical test to infer the causality of target/phenotype correlation
      from small molecule phenotypic screens.
AB  - MOTIVATION: Cell-based phenotypic screens using small molecule inhibitors is an
      important technology for early drug discovery if the relationship between the
      disease-related cellular phenotype and inhibitors' biological targets can be
      determined. However, chemical inhibitors are rightfully believed to be less
      specific than perturbation by biological agents, such as antibody and small
      inference RNA. Therefore, it is often a challenge in small molecule phenotypic
      screening to infer the causality between a particular cellular phenotype and the
      inactivation of the responsible protein due to the off-target effect of the
      inhibitors. RESULTS: In this article, we present a Roche in-house effort of
      screening 746 structurally diverse compounds for their cytotoxicity in HeLa cells
      measured by high content imaging technology. These compounds were also
      systematically profiled for the targeted and off-target binding affinity to a
      panel of 25 pre-selected protein kinases in a cell-free system. In an effort to
      search for the kinases whose activities are crucial for cell survival, we found
      that the simple association method such as the chi-square test yields a large
      number of false positives because the observed cytotoxic phenotype is likely to
      be the result of promiscuous action of less specific inhibitors instead of true
      consequence of inactivation of single relevant target. We demonstrated that a
      stratified categorical data analysis technique such as the Cochran-Mantel
      Haenszel test is an effective approach to extract the meaningful biological
      connection from the spurious correlation resulted from confounding covariates.
      This study indicates that, empowered by appropriate statistical adjustment, small
      molecule inhibitor perturbation remains a powerful tool to pin down the relevant
      biomarker for drug safety and efficacy research. CONTACT: xin.wei@roche.com
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22155865
TI  - B-SOLANA: an approach for the analysis of two-base encoding bisulfite sequencing
      data.
AB  - SUMMARY: Bisulfite sequencing, a combination of bisulfite treatment and high
      throughput sequencing, has proved to be a valuable method for measuring DNA
      methylation at single base resolution. Here, we present B-SOLANA, an approach for
      the analysis of two-base encoding (colorspace) bisulfite sequencing data on the
      SOLiD platform of Life Technologies. It includes the alignment of bisulfite
      sequences and the determination of methylation levels in CpG as well as non-CpG
      sequence contexts. B-SOLANA enables a fast and accurate analysis of large raw
      sequence datasets. AVAILABILITY AND IMPLEMENTATION: The source code, released
      under the GNU GPLv3 licence, is freely available at
      http://code.google.com/p/bsolana/. CONTACT: b.kreck@ikmb.uni-kiel.de
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22155866
TI  - InFiRe -- a novel computational method for the identification of insertion sites
      in transposon mutagenized bacterial genomes.
AB  - MOTIVATION: InFiRe, Insertion Finder via Restriction digest, is a novel software
      tool that allows for the computational identification of transposon insertion
      sites in known bacterial genome sequences after transposon mutagenesis
      experiments. The approach is based on the fact that restriction endonuclease
      digestions of bacterial DNA yield a unique pattern of DNA fragments with defined
      sizes. Transposon insertion changes the size of the hosting DNA fragment by a
      known number of base pairs. The exact size of this fragment can be determined by
      Southern blot hybridization. Subsequently, the position of insertion can be
      identified with computational analysis. The outlined method provides a solid
      basis for the establishment of a new high-throughput technology. AVAILABILITY AND
      IMPLEMENTATION: The software is freely available on our web server at
      www.infire.tu-bs.de. The algorithm was implemented in the statistical programming
      language R. For the most flexible use, InFiRe is provided in two different
      versions. A web interface offers the convenient use in a web browser. In
      addition, the software and source code is freely available for download as R
      packages on our website. CONTACT: m.steinert@tu-bs.de SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 22155867
TI  - Identifying quantitative trait loci via group-sparse multitask regression and
      feature selection: an imaging genetics study of the ADNI cohort.
AB  - MOTIVATION: Recent advances in high-throughput genotyping and brain imaging
      techniques enable new approaches to study the influence of genetic variation on
      brain structures and functions. Traditional association studies typically employ
      independent and pairwise univariate analysis, which treats single nucleotide
      polymorphisms (SNPs) and quantitative traits (QTs) as isolated units and ignores
      important underlying interacting relationships between the units. New methods are
      proposed here to overcome this limitation. RESULTS: Taking into account the
      interlinked structure within and between SNPs and imaging QTs, we propose a novel
      Group-Sparse Multi-task Regression and Feature Selection (G-SMuRFS) method to
      identify quantitative trait loci for multiple disease-relevant QTs and apply it
      to a study in mild cognitive impairment and Alzheimer's disease. Built upon
      regression analysis, our model uses a new form of regularization, group l(2,1)
      norm (G(2,1)-norm), to incorporate the biological group structures among SNPs
      induced from their genetic arrangement. The new G(2,1)-norm considers the
      regression coefficients of all the SNPs in each group with respect to all the QTs
      together and enforces sparsity at the group level. In addition, an l(2,1)-norm
      regularization is utilized to couple feature selection across multiple tasks to
      make use of the shared underlying mechanism among different brain regions. The
      effectiveness of the proposed method is demonstrated by both clearly improved
      prediction performance in empirical evaluations and a compact set of selected SNP
      predictors relevant to the imaging QTs. AVAILABILITY: Software is publicly
      available at: http://ranger.uta.edu/%7eheng/imaging-genetics/.

PMID- 22155868
TI  - GenomeRunner: automating genome exploration.
AB  - MOTIVATION: One of the challenges in interpreting high-throughput genomic studies
      such as a genome-wide associations, microarray or ChIP-seq is their open-ended
      nature-once a set of experimentally identified regions is identified as
      statistically significant, at least two questions arise: (i) besides P-value, do
      any of these significant regions stand out in terms of biological implications?
      (ii) Does the set of significant regions, as a whole, have anything in common
      genome wide? These issues are difficult to address because of the growing number
      of annotated genomic features (e.g. single nucleotide polymorphisms,
      transcription factor binding sites, methylation peaks, etc.), and it is difficult
      to know a priori which features would be most fruitful to analyze. Our goal is to
      provide partial automation of this process to begin examining associations
      between experimental features and annotated genomic regions in a hypothesis-free,
      data-driven manner. RESULTS: We created GenomeRunner-a tool for automating
      annotation and enrichment of genomic features of interest (FOI) with annotated
      genomic features (GFs), in different organisms. Besides simple association of
      FOIs with known GFs GenomeRunner tests whether the enriched FOIs, as a group, are
      statistically associated with a large and growing set of genomic features.
      AVAILABILITY: GenomeRunner setup files and source code are freely available at
      http://sourceforge.net/projects/genomerunner. CONTACT: mikhail-dozmorov@omrf.org;
      Jonathan-Wren@omrf.org; jdwren@gmail.com SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 22155869
TI  - Identification and removal of ribosomal RNA sequences from metatranscriptomes.
AB  - SUMMARY: Here, we present riboPicker, a robust framework for the rapid, automated
      identification and removal of ribosomal RNA sequences from metatranscriptomic
      datasets. The results can be exported for subsequent analysis, and the databases
      used for the web-based version are updated on a regular basis. riboPicker
      categorizes rRNA-like sequences and provides graphical visualizations and tabular
      outputs of ribosomal coverage, alignment results and taxonomic classifications.
      AVAILABILITY AND IMPLEMENTATION: This open-source application was implemented in
      Perl and can be used as stand-alone version or accessed online through a user
      friendly web interface. The source code, user help and additional information is
      available at http://ribopicker.sourceforge.net/. CONTACT:
      rschmied@sciences.sdsu.edu; rschmied@sciences.sdsu.edu SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 22155870
TI  - Control-FREEC: a tool for assessing copy number and allelic content using next
      generation sequencing data.
AB  - SUMMARY: More and more cancer studies use next-generation sequencing (NGS) data
      to detect various types of genomic variation. However, even when researchers have
      such data at hand, single-nucleotide polymorphism arrays have been considered
      necessary to assess copy number alterations and especially loss of heterozygosity
      (LOH). Here, we present the tool Control-FREEC that enables automatic calculation
      of copy number and allelic content profiles from NGS data, and consequently
      predicts regions of genomic alteration such as gains, losses and LOH. Taking as
      input aligned reads, Control-FREEC constructs copy number and B-allele frequency
      profiles. The profiles are then normalized, segmented and analyzed in order to
      assign genotype status (copy number and allelic content) to each genomic region.
      When a matched normal sample is provided, Control-FREEC discriminates somatic
      from germline events. Control-FREEC is able to analyze overdiploid tumor samples
      and samples contaminated by normal cells. Low mappability regions can be excluded
      from the analysis using provided mappability tracks. AVAILABILITY: C++ source
      code is available at: http://bioinfo.curie.fr/projects/freec/ CONTACT:
      freec@curie.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 22155871
TI  - RRBSMAP: a fast, accurate and user-friendly alignment tool for reduced
      representation bisulfite sequencing.
AB  - SUMMARY: Reduced representation bisulfite sequencing (RRBS) is a powerful yet
      cost-efficient method for studying DNA methylation on a genomic scale. RRBS
      involves restriction-enzyme digestion, bisulfite conversion and size selection,
      resulting in DNA sequencing data that require special bioinformatic handling.
      Here, we describe RRBSMAP, a short-read alignment tool that is designed for
      handling RRBS data in a user-friendly and scalable way. RRBSMAP uses wildcard
      alignment, and avoids the need for any preprocessing or post-processing steps. We
      benchmarked RRBSMAP against a well-validated MAQ-based pipeline for RRBS read
      alignment and observed similar accuracy but much improved runtime performance,
      easier handling and better scaling to large sample sets. In summary, RRBSMAP
      removes bioinformatic hurdles and reduces the computational burden of large-scale
      epigenome association studies performed with RRBS. AVAILABILITY:
      http://rrbsmap.computational-epigenetics.org/ http://code.google.com/p/bsmap/
      CONTACT: wl1@bcm.tmc.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 22155872
TI  - SomaticSniper: identification of somatic point mutations in whole genome
      sequencing data.
AB  - MOTIVATION: The sequencing of tumors and their matched normals is frequently used
      to study the genetic composition of cancer. Despite this fact, there remains a
      dearth of available software tools designed to compare sequences in pairs of
      samples and identify sites that are likely to be unique to one sample. RESULTS:
      In this article, we describe the mathematical basis of our SomaticSniper software
      for comparing tumor and normal pairs. We estimate its sensitivity and precision,
      and present several common sources of error resulting in miscalls. AVAILABILITY
      AND IMPLEMENTATION: Binaries are freely available for download at
      http://gmt.genome.wustl.edu/somatic-sniper/current/, implemented in C and
      supported on Linux and Mac OS X. CONTACT: delarson@wustl.edu; lding@wustl.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22155873
TI  - Minimally invasive training in urologic oncology.
AB  - Use of minimally invasive surgical (MIS) techniques continues to expand in the
      field of urologic oncology; however, proficiency in these  techniques is subject
      to a learning curve. Current training paradigms have incorporated MIS, but in a
      non-standardized fashion. Residency  work-hour restrictions and ethical concerns
      may influence efforts to deliver adequate training during a defined residency
      period. Post-residency fellowships or mini-courses may help urologists gain
      proficiency in these skills, but are time-consuming and may not provide adequate
      exposure.  Surgical simulation with dry labs and augmentation with virtual
      reality are important adjuncts to operative training for MIS. The urologic 
      oncologist must be familiar with open and MIS  techniques to effectively treat
      cancer in the least morbid way possible and adapt to the ever-changing field of
      MIS with dynamic training  paradigms.

PMID- 22155874
TI  - Hyperbaric oxygen therapy for the management of hemorrhagic radio-induced
      cystitis.
AB  - OBJECTIVES: Radio-induced cystitis (RADC) is an inflammatory bladder disease that
      presents as anemic-hematuria in its most  serious form. Classic treatments can
      not control the disease in the mid-to-long term because they don't treat the
      pathogenesis  of the disease. Thus, we evaluated the effectiveness of hyperbaric
      oxygen (HBO) therapy as a potential treatment for patients with RADC. METHODS:
      This prospective study included 38 patients, 21 men and 17 women, mean age of
      66.5 years(46-75), who had been subjected to pelvic  radiotherapy (RT), with the
      diagnosis of RADC with or without radio-induced proctitis (RADP), gross hematuria
      and lower urinary tract symptoms. HBO treatment was applied in a multiplace
      chamber; patients breathed pure oxygen (100%) at 2-2.5  atmospheres  of pressure
      (ATAs). Patients received an average of 31.2 sessions (10-48 sessions) and the
      median follow-up period  was 56 months (4-72 months). RESULTS: Hematuria was
      completely resolved in 34 of the 38 patients. After HBO 6 patients required
      readmission, 5 for anemic hematuria and 1 for acute  obstructive pyelonephritis.
      In general, patients tolerated treatment well; however, one patient experienced
      barotrauma requiring myringotomy. CONCLUSIONS: HBO can be used to satisfactorily
      treat RADC, leading to clinical improvements that begin during the initial
      sessions in the majority of  cases, and with a more than acceptable level of
      patient tolerance.

PMID- 22155875
TI  - Decision analysis for economic evaluation of the management of chronic
      obstructive uropathy.
AB  - OBJECTIVES: To test which is the best treatment for chronic obstructive uropathy:
      urinary diversion using a conventional double-J ureteral stent or  the metal
      thermo-expandable MemokathTM 051 prosthesis. METHODS: We collected cost data of
      the insertion of a double-J stent taking into account preoperative and
      postoperative visits and surgery.  Structural, medical, consumables and the
      prosthesis costs were considered. The estimated survival of the patient, number
      of spare stents and cost of each  therapeutic measure were computed. Then, a
      simulation of the cost of inserting a MemokathTM 051 prosthesis was conducted,
      based on data of ureteral catheterization. We performed a decision tree and Cost
      Effectiveness economic analysis to measure the effectiveness of both health
      interventions. RESULTS: Cost data of each procedure were: 1275.44 ? for the
      double J catheter in a program of day case surgery (DCS), 4865.16 ? for  the
      metal  thermo-expandable prosthesis as DCS, and 1424.52?for the double J stent
      with 1 day admission and 5014.24 ? for the prosthesis with 1  day admission. The
      cost difference between ureteral stent and metal thermo-expandable prosthesis is
      3589.72 ? per treatment for the ureteral stent as DCS. CONCLUSIONS: Despite its
      high initial cost, the metal thermo-expandable prosthesis potentially offers
      economic advantages over the  conventional double-J ureteral stent in the
      treatment of long evolution ureteral obstruction. After the third change of
      double-J stent, and  if the patient survival is long enough, the metal prosthesis
      as DCS should be the most cost effective option.

PMID- 22155876
TI  - Thrombocytosis and hematocrit as prognostic factors in renal carcinoma.
AB  - OBJECTIVE: To examine the connection between preoperative thrombocytosis and
      hematocrit and survival in a group of patients operated for renal cell 
      carcinoma. METHODS: Retrospective study with descriptive and statistical analysis
      of 139 patients with renal cell carcinoma treated surgically over the last 4 
      years in our Urology clinical unit. 116 (83,45%)were diagnosed at a localized
      clinical stage, whereas 23 (16,54%)  presented as locally advanced or metastatic
      disease. We collected data about survival and time on surveillance, imaging and
      histological characteristics  of the tumor and analytical parameters. Data were
      analyzed by the SPSS statistical software. RESULTS: The average platelet count
      and hematocrit before surgery were 260,930 cells/mm3 and 41.10%, respectively. We
      found a statistical  correlation between platelet count at the time of diagnosis
      and survival. Patients with platelet counts higher than 350,000 cells/mm3 had  a
      poor survival (OR: 2.94; CI 95% 1.04- 8.27). We also found that patients with
      high hematocrit at diagnosis presented a  lower risk of death   (OR: 0.92; CI 95%
      0.85-  0.99). The global survival at the end of the study was 88.4%. Multivariate
      analysis  did not show any significant  result  because of the low number of
      deaths. CONCLUSION: The presence of high platelet count or low hematocrit
      correlate with poor survival in a group of surgically treated renal cell 
      carcinoma patients. Nevertheless more studies with longer surveillance and higher
      number of patients are needed.

PMID- 22155877
TI  - Transperitoneal laparoscopic management of urinary tract stone disease:
      experience in a third level hospital.
AB  - OBJECTIVES: The aim of this paper is to describe the clinical-surgical
      characteristics of patients who underwent laparoscopic procedures for the  
      management of urinary tract stone disease when performing extracorporeal,
      percutaneous or endourological procedures was not available. METHODS: A
      descriptive study based on information from the medical records of patients who
      underwent surgical laparoscopic management of urinary  stone disease between
      January 2001 and May 2010 at a third level hospital. Epidemiological, clinical
      and procedure-related variables were taken  from the medical records. Univariate
      analysis was performed with the statistical software STATA 10.1. RESULTS: There
      were 29 procedures (27 patients) for treatment of urinary stone disease in
      adults. The average age was 45 years. 55% of  patients  were men. 17 stones were
      found on the right side, 5 were pyelic, 19 of the proximal ureter, 4 of the
      medium ureter and 1 distal. All patients  underwent laparoscopic surgery as first
      surgical option. Average operative time was 142 +/- 32 minutes. Three procedures
      were defined as failures.  Hospital stay presented a median of 2 days. There were
      seven complications. CONCLUSION: Laparoscopic surgery is a good surgical option
      for the management of urinary tract stone disease in adults.

PMID- 22155878
TI  - Usefulness of bladder-prostate ultrasound in the diagnosis of
      obstruction/hyperactivity in males with BPH.
AB  - OBJECTIVE: To determine the utility of prostate ultrasound in the diagnosis of
      infravesical obstruction (IVO) and detrusor hyperactivity(DH). METHODS:
      Prospective study with 39 patients consulting for LUTS. Clinical history was
      compiled, IPSS was determined, a digital rectal exam was  performed, abdominal
      ultrasound was used to calculate detrusor thickness/weight, prostate volume, and
      middle lobe length (MLL). Urodynamic study  (UD) was  performed with
      determination of the Abrams-Griffiths number and ICS nomogram. Mean values were
      compared with Mann-Whitney U-test,  and ROC curves were  plotted determining the
      cutoff points for optimum sensitivity/specificity. RESULTS: Mean age was 63.1
      years (SD: 7.8), with a mean IPSS score of 14 (SD: 6). 53.8% of the patients
      presented IVO at UD  evaluation, and  43.6% DH.  The differences between free
      flowmetry Qmax(p=0.015) and MLL (p=0.003) between patients with and without IVO
      proved  significant. The ROC curves  yielded  an AUC for middle lobe length of
      0.772, with a maximum sensitivity and specificity cutoff point at 10.5 mm
      (sensitivity 90%, specificity  73%,  PPV 76%, NPV 85%). There were no significant
      differences in any parameter between patients with and without DH. CONCLUSION:
      Ultrasound MLL measurement in patients with LUTS offers high
      sensitivity/specificity in diagnosing IVO, with a cutoff point of 10.5 mm.  In
      our study it wasn't effective in the noninvasive diagnosis of DH.

PMID- 22155879
TI  - Bilateral primary renal lymphoma: case report and bibliographic review.
AB  - OBJECTIVE: To review the presentation, diagnosis and treatment of primary renal
      lymphoma through a new case report. METHODS: We report the case of a 73-year-old
      man who presented at A&E with constitutional symptoms and weight loss of 9
      kilograms over 3   months RESULTS: Laboratory analysis showed impaired renal
      function, anemia and hypercalcemia. Imaging tests showed a large solid mass in
      the right perirenal  area with infiltration of the parenchyma and Gerota's fascia
      surrounding the hilum of the kidney, as well as a solid mass in the inferior pole
      of the  left kidney. Pathology showed the presence of lymphoid-like monomorphic
      cells. After establishing the diagnosis of bilateral primary renal  lymphoma  it
      was decided to start treatment with CHOP-Rituximab-type combination chemotherapy.
      CONCLUSIONS: Primary renal lymphoma is a rare entity and the diagnostic technique
      of choice is CT. Definitive diagnosis is confirmed on histology.  In view of its
      aggressive nature and poor prognosis, it is important to make an early diagnosis
      in order to start treatment promptly. The treatment  of choice is systemic
      chemotherapy using a CHOP regimen.

PMID- 22155880
TI  - Colpocleisis in vesico-vaginal radiation fistula.
AB  - OBJECTIVE: To assess Latzko's colpocleisis with bilateral Martius flap as a
      solution for vesico vaginal fistula secondary to radiotherapy. METHOD: 65 year
      old woman with past medical history of cervix adenocarcinoma treated with
      hysterectomy, pelvic radiotherapy and brachytherapy. She  also had terminal
      colostomy for recto-vaginal fistula. She complained of a 2-year history of
      continuous urinary escape through vagina. On  cistoscopy, the ureteral orifices
      were close to the loss of substance. Colpocleisis following Latzko's technique
      was performed. RESULTS: Complete resection of the fistulous tract and tension
      free closure is a surgical challenge not always achieved, and with a high
      recurrence rate.  Latzko's colpocleisis is a simple and safe option in patients
      that have previously undergone a hysterectomy. Bilateral Martius flap increases
      vascular  support of the affected tissues, which is of pivotal importance in
      patients subjected to radiotherapy. CONCLUSION: Latzko's colpocleisis is a valid
      therapeutic option in those histerectomised patients with vesico vaginal fistulas
      due to radiotherapy who  are not eligible for fistulorraphy.

PMID- 22155881
TI  - Stauffer syndrome in transitional cell carcinoma of the bladder.
AB  - OBJECTIVE: To present the case of a woman with the diagnosis of transitional cell
      carcinoma of the bladder and Stauffer's syndrome. METHOD: The clinical and
      radiological files were analyzed, and a bibliographic review was performed.
      RESULTS: We present an 82 year old female with a four month history of hematuria,
      presenting in the emergency room where abnormal hepatic  profile was documented.
      The diagnosis of bladder tumor was established and she underwent transurethral
      bladder resection. The pathological report  showed transitional cell bladder
      cancer, with complete resection. Metastasis and infectious hepatic dysfunction
      were discarded. The hepatic profile  became normal days later, so Stauffer's
      syndrome diagnosis was performed. CONCLUSION: This is the first report to our
      knowledge of this paraneoplastic syndrome in transitional cell carcinoma of the
      bladder.

PMID- 22155882
TI  - Primary mucinous neoplasms of the renal pelvis: report of two cases.
AB  - OBJECTIVE: To describe the histopathologic features and clinical presentation of
      two primary mucinous neoplasms of the renal pelvis. METHODS: We describe two
      cases and its correlation with histopathologic findings. RESULTS: Primary
      mucinous neoplasm of the renal pelvis was diagnosed  by histopathology in two
      patients who received medical treatment for abdominal tumor. CONCLUSIONS: Primary
      mucinous neoplasms of the renal pelvis are extremely rare; the first symptom is
      usually abdominal growth, followed by hematuria  and flank pain; it is difficult
      to suspect the diagnosis before surgery, because in most cases it is established
      with biopsy.

PMID- 22155883
TI  - Ureterocele. Intravenous urography images.

PMID- 22155884
TI  - Nephrectomy for terminal hydronephrosis.

PMID- 22155885
TI  - Obituary John Blandy 1927-2011.

PMID- 22155886
TI  - Genotoxic and cytotoxic effects of storax in vitro.
AB  - The aim of this study is to investigate the effects of the storax balsam, which
      is a kind of sweet gum obtained from the Liquidambar orientalis Mill trees, on
      cell viability, cytotoxicity and genotoxicity in human lymphocyte in vitro. We
      studied the genotoxic effects of the extract of storax balsam (SE) using sister
      chromatid exchange (SCE) test system. Also the cytotoxic and inhibitory effects
      on cell proliferation of SE were evaluated using lactate dehydrogenase (LDH)
      assay and cell proliferation (WST-1) assay. The SCE frequency was increased when
      the cells were treated with 1.6 and 4.0 ug/mL SE concentrations (p < 0.05).
      Moreover, treatment of the cells with the same concentrations significantly
      depleted the cell number at 24th and 48th hours and elevated the LDH levels (p <
      0.05) at 48th hour. These results suggest that SE can be used as an alternative
      antibacterial and antipathogenic agent due to its cytotoxic and genotoxic
      effects.

PMID- 22155887
TI  - Evaluation of total oxidative status and total antioxidant capacity in patients
      with endemic fluorosis.
AB  - The objective of the present study was to determine the plasma total oxidative
      status (TOS) and total antioxidant capacity (TAC) in patients with endemic
      fluorosis. A total of 79 (35 males and 44 females; mean age 44.0 +/- 11.9 years)
      patients with endemic fluorosis and 55 (23 males and 32 females; mean age 48.3 +/
      8.5 years) age-, sex- and body mass index-matched healthy controls were included
      in this study. The urine fluoride levels and plasma TOS and TAC levels were
      measured. The urine fluoride levels of fluorosis patients were significantly
      higher than control subjects as expected (1.91 +/- 0.15 vs. 0.49 +/- 0.13 mg/L,
      respectively; p < 0.001). TOS was significantly higher in fluorosis group than in
      control group (17.55 +/- 3.82 vs. 15.06 +/- 4.31 MUmol H(2)O(2) Eq/L,
      respectively; p = 0.001). TAC was significantly lower in fluorosis group than in
      control group (1.60 +/- 0.36 vs. 1.82 +/- 0.51 mmol Trolox Eq/L, respectively; p
      = 0.004). Oxidative stress index (OSI) was significantly higher in fluorosis
      group than in control group (11.5 +/- 3.8 vs. 8.8 +/- 3.7, respectively; p <
      0.001). Correlation analysis in all the groups indicated that TAC was negatively
      correlated with urine fluoride (r = -0.25, p = 0.003), TOS was positively
      correlated with urine fluoride (r = 0.34, p < 0.001) and OSI was positively
      correlated with urine fluoride (r = 0.36, p < 0.001). The results of our study
      demonstrate that oxidative stress plays an important role in the pathogenesis of
      the endemic fluorosis.

PMID- 22155888
TI  - Controlled clustering in metal nanorod arrays leads to strongly enhanced field
      emission characteristics.
AB  - We show that controlled clustering in electrochemically grown silver nanorods
      results in up to 50% enhancement in their field emission performance. Larger
      cluster size and nanorod length lead to a lower turn-on electric field, a higher
      current density and a larger enhancement factor. However, beyond a critical
      length (~30 um), the nanorods begin to form disordered ridges instead of well
      separated conical clusters and the field emission performance proceeds to
      deteriorate. With the help of finite element modelling, we show that a larger
      cluster size indeed leads to an enhanced electric field at the cluster edges,
      effectively reducing screening effects and thereby enhancing the field emission
      performance. Though our present work pertains to silver nanorods, a similar
      clustering of nanorods is observed in many types of electrochemically grown
      nanorods, and even in carbon nanotubes and Si nanowires grown by other
      techniques. Hence, we expect this study to have general applicability in the
      design of better nanorod-based field emitters.

PMID- 22155889
TI  - Two novel cis-elements involved in hepatocyte nuclear factor 4alpha regulation of
      acyl-coenzyme A:cholesterol acyltransferase 2 expression.
AB  - Acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) is important for
      cholesterol ester synthesis and secretion. A previous study revealed that ACAT2
      gene promoter activity was upregulated by hepatocyte nuclear factor 4alpha
      (HNF4alpha) through two sites around -247 and -311 of ACAT2 gene promoter. Here,
      we identified two novel cis-elements, site I (-1006 to -898) and site II (-38 to 
      29), which are important for HNF4alpha effect. In HepG2 cells, mutation of site I
      decreased ACAT2 gene promoter activity to one-fifth of that of the wild type,
      while mutation of site II reduced promoter activity to less than one-tenth of
      that of the wild type. In 293T cells, mutation of these two cis-elements
      profoundly impaired the HNF4alpha induction effect. When either of these two
      elements was inserted into pGL3-promoter, HNF4alpha induced promoter activity
      through the inserted element, while mutation of the element impaired HNF4alpha
      induction effect. In electrophoretic mobility shift assay and chromatin
      immunoprecipitation experiment, HNF4alpha bound to these two elements. Thus, the
      two cis-elements are important for HNF4alpha effect on ACAT2 gene transcription.
      We also showed that HNF4alpha positively regulates ACAT2 gene expression at mRNA
      level. Overexpression of HNF4alpha increased ACAT2 expression, whereas knockdown
      of HNF4alpha decreased ACAT2 expression. Peroxisome proliferator-activated
      receptor gamma coactivator 1alpha (PCG1alpha), a coactivator of HNF4alpha,
      increased ACAT2 expression, while small heterodimer partner (SHP), a corepressor
      of HNF4alpha, decreased ACAT2 expression. These results provide more insights
      into transcriptional regulation of ACAT2 expression.

PMID- 22155890
TI  - Measurement of interchain and intrachain exciton hopping barriers in luminescent
      polymer.
AB  - The integrated photoluminescence intensity in thin films of 'Super Yellow'
      copolymer has been analyzed using a Mott-like temperature dependence. This has
      enabled us to observe contributions from two emission channels, indicative of
      exciton recombination proceeding from two distinct origins. At high temperature,
      interchain thermally activated exciton energy transfer and migration dominates,
      resulting in large scale quenching of the integrated emission intensity and hence
      the photoluminescence quantum yield. However, at relatively low temperature, an
      additional increase of the integrated emission intensity occurs. This new channel
      of emission has been attributed to recombination from excitons where intrachain
      exciton energy transfer between adjacent subunits of the copolymer backbone
      becomes hindered. The activation energy barriers that control both of these
      emission channels have been obtained and are correlated with chain backbone
      degrees of freedom.

PMID- 22155891
TI  - Competition Commission considers investigating private health market.

PMID- 22155892
TI  - Funding crisis forces Cancer Research UK to cut spending by 10%.

PMID- 22155893
TI  - Intonational patterns of nonverbal vocalizations in people with dementia.
AB  - Nonverbal vocalizations in dementia are important clinically since they generally
      have been regarded as disruptive behavior that is disturbing. The aim of the
      present study is to describe the interactional pattern, including the prosodic
      package, of nonverbal vocalizations in a participant in a late stage of dementia.
      The acoustic analysis shows that the vocalizations do not differ significantly
      from the verbal utterances regarding mean fundamental frequency or pitch range.
      The mean fundamental frequency, F0, of the utterances from Anna was significantly
      higher than the mean F0 from the other elderly participants. The analysis
      demonstrates that there is a singing-like type of vocalizations that does not
      resemble the previously described patterns of nonverbal vocalizations. This
      pattern of the nonverbal vocalization does not resemble the intonation of Anna's
      verbal utterances. The other participants perceive Anna's vocalizations as
      potentially meaningful turns. Nonverbal vocalizations in clinical settings should
      be taken as communicative contributions.

PMID- 22155894
TI  - Comparison of informant reports and neuropsychological assessment in mild
      cognitive impairment.
AB  - The aim of this retrospective study was to investigate the accuracy of informant
      reports on cognitive status in mild cognitive impairment (MCI) by comparing the
      subjective evaluation made by patients' relatives with the objective results of
      neuropsychological assessment. We enrolled 119 MCI outpatients and their
      relatives. Cognitive impairment was assessed by a battery of standardized
      neuropsychological tests. Informant reports on cognitive functioning were
      obtained by means of a structured interview. Subjective and objective evaluations
      of cognitive status were rated according to the same scoring system in order to
      enable comparison. All but one relative reported cognitive dysfunctions at the
      interview, but the kind of cognitive profile emerging from their reports was
      quite different from the one highlighted by neuropsychological assessment. A
      subjective evaluation of cognitive status based on informant reports could
      therefore be useful to identify patients with MCI but is unable to define MCI
      subtypes.

PMID- 22155895
TI  - Storytelling as a model of conversation for people with dementia and caregivers.
AB  - Storytelling is an important method of communication at all stages of life.
      Sharing narratives about lived events and experiences provides topics of
      conversation and opportunities for connecting with other people. In this article,
      we apply a conventional model of storytelling to the verbal reminiscences of
      older people with a dementia diagnosis. Their stories retain the conventional
      structure, suggesting that storytelling, which is an enjoyable and engaging
      social activity, can provide a conversation model for people with dementia.

PMID- 22155896
TI  - Uniform and position-controlled InAs nanowires on 2" Si substrates for transistor
      applications.
AB  - This study presents a novel approach for indirect integration of InAs nanowires
      on 2'' Si substrates. We have investigated and developed epitaxial growth of InAs
      nanowires on 2'' Si substrates via the introduction of a thin yet high-quality
      InAs epitaxial layer grown by metalorganic vapor phase epitaxy. We demonstrate
      well-aligned nanowire growth including precise position and diameter control
      across the full wafer using very thin epitaxial layers (<300 nm). Statistical
      analysis results performed on the grown nanowires across the 2'' wafer size
      verifies our full control on the grown nanowire with 100% growth yield. From the
      crystallographic viewpoint, these InAs nanowires are predominantly of wurtzite
      structure. Furthermore, we show one possible device application of the
      aforementioned structure in vertical wrap-gated field-effect transistor geometry.
      The vertically aligned InAs nanowires are utilized as transistor channels and the
      InAs epitaxial layer is employed as the source contact. A high uniformity of the
      device characteristics for numerous transistors is further presented and RF
      characterization of these devices demonstrates an f(t) of 9.8 GHz.

PMID- 22155897
TI  - Psychophysical parameters of a multidimensional pain scale in newborns.
AB  - The Premature Infant Pain Profile (PIPP) is a promising multidimensional tool for
      comparison and testing of new technologies in newborn pain assessment studies
      since it may adhere to basic psychophysical parameters of intensity, direction,
      reactivity, regulation and slope described in analyses of physiological pain
      indicators. The aim of this study was to evaluate whether these psychophysical
      parameters can be achieved using the PIPP in acute pain assessment. Thirty-six
      healthy term newborn infants were conveniently sampled whilst being videotaped
      before, during and after heel prick blood sampling. The images were blind-scored
      by three trained independent raters and scored against the PIPP. The PIPP and its
      facial action indicators met the parameters of intensity, reactivity and
      regulation (all p < 0.001). The heart rate variability did not meet any parameter
      (all p > 0.05). The oxygen saturation variability met only the intensity
      parameter (p < 0.05). The behavioural state indicator met all parameters and had
      the best correlation to the psychophysical parameters of all indicators of PIPP
      (all p < 0.001). We concluded that the overall PIPP meets the assumptions of
      these psychophysical parameters, being the behavioural state indicator which best
      fit the model.

PMID- 22155898
TI  - Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the fetal
      compartment (placenta and amniotic fluid).
AB  - HIV resides within anatomical 'sanctuary sites' where local drug exposure and
      viral dynamics may differ significantly from the systemic compartment. Widespread
      implementation of antiretroviral therapy has seen a significant decline in the
      incidence of mother-to-child transmission (MTCT) of HIV. In addition to
      suppression of maternal plasma/genital viral loads, antiretroviral agents that
      cross the placenta and achieve adequate concentrations in the fetal compartment
      may exert a greater prophylactic effect. Penetration of antiretrovirals in the
      fetal compartment is expressed by accumulation ratios derived from the
      measurement of drug concentrations in paired maternal plasma and umbilical cord
      samples. The nucleoside analogues and nevirapine accumulate extensively in cord
      blood and in the surrounding amniotic fluid, whereas the protease inhibitors
      (PIs) exhibit low-to-moderate placental accumulation. Early data suggest that
      high placental/neonatal concentrations are achieved with raltegravir, but to a
      lesser extent with etravirine and maraviroc (rank order of accumulation:
      raltegravir/nucleoside reverse transcriptase inhibitor [tenofovir >
      zidovudine/lamivudine/emtricitabine/stavudine/abacavir] > non-nucleoside reverse
      transcriptase inhibitor [nevirapine > etravirine] > PI > maraviroc/enfuvirtide).
      More comprehensive in vivo pharmacokinetic data are required to justify the
      potential use of these agents as safe and effective options during pregnancy.

PMID- 22155899
TI  - Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the male
      and female genital tract.
AB  - HIV resides within anatomical 'sanctuary sites', where local drug exposure and
      viral dynamics may differ significantly from the systemic compartment. Suboptimal
      antiretroviral concentrations in the genital tract may result in
      compartmentalized viral replication, selection of resistant mutations and
      possible re-entry of wild-type/resistant virus into the systemic circulation.
      Therefore, achieving adequate antiretroviral exposure in the genital tract has
      implications for the prevention of sexual and vertical transmission of HIV.
      Penetration of antiretrovirals in the genital tract is expressed by accumulation
      ratios derived from the measurement of drug concentrations in time-matched
      seminal plasma/cervicovaginal fluid and plasma samples. Penetration varies by
      gender and may be drug (as opposed to class) specific with high interindividual
      variability. Concentrations in seminal plasma are highest for nucleoside
      analogues and lowest for protease inhibitors and efavirenz. Seminal accumulation
      of newer agents, raltegravir and maraviroc, is moderate (rank order of
      accumulation is nucleoside/nucleotide reverse transcriptase inhibitors
      [lamivudine/zidovudine/tenofovir/didanosine > stavudine/abacavir] > raltegravir >
      indinavir/maraviroc/nevirapine >> efavirenz/protease inhibitors
      [amprenavir/atazanavir/darunavir > lopinavir/ritonavir > saquinavir] >
      enfuvirtide). In the female genital tract, the nucleoside analogues exhibit high
      accumulation ratios, whereas protease inhibitors have limited penetration;
      however, substantial variability exists between individuals and study centres.
      Second generation non-nucleoside reverse transcriptase inhibitor etravirine, and
      maraviroc and raltegravir, demonstrate effective accumulation in cervicovaginal
      secretions (rank order of accumulation is nucleoside/nucleotide reverse
      transcriptase inhibitor [zidovudine/lamivudine/didanosine >
      emtricitabine/tenofovir] > indinavir > maraviroc/raltegravir/darunavir/etravirine
      > nevirapine/abacavir > protease inhibitors [amprenavir/atazanavir/ritonavir] >
      lopinavir/stavudine/efavirenz > saquinavir).

PMID- 22155900
TI  - HBV genotypes: relevance to natural history, pathogenesis and treatment of
      chronic hepatitis B.
AB  - Although chronic HBV infection is the leading cause of chronic liver disease and
      death worldwide, there are substantial differences in its clinical courses
      regarding prevalence, mode of transmission, characteristics of each phase,
      responses to antiviral therapy, and development of cirrhosis and hepatocellular
      carcinoma, according to geographical areas (Asia versus Western Europe and North
      America versus Africa). Furthermore, the clinical course in infected individuals
      depends on a complex interplay among various factors including viral, host,
      environmental and other factors. Recently, understanding of molecular
      characteristics of the prevailing HBV genotypes, frequently accompanied mutations
      and their clinical implications might explain these geographical differences more
      pertinently. Hence, in this article, we review the global epidemiology and the
      natural history of HBV infection, with emphasis on summarizing the different HBV
      genotypes according to regions.

PMID- 22155901
TI  - Impact of HCV protease-inhibitor-based triple therapy for chronic HCV genotype 1
      infection.
AB  - Boceprevir and telaprevir are the first HCV protease inhibitors to be approved
      for the treatment of chronic hepatitis C genotype 1 infection. These drugs must
      be used in combination with pegylated interferon plus ribavirin (P/R) to maximize
      efficacy and prevent the emergence of resistance-associated variants (RAVs). In
      randomized, placebo-controlled international studies in treatment-naive and
      previously treated HCV patients, treatment with either boceprevir- or telaprevir
      based triple therapy regimens significantly increased sustained virological
      response rates compared with placebo plus P/R. Protease inhibitors have the
      potential, not only to significantly increase cure rates among patients with
      genotype 1 infection, but also to reduce the duration of treatment for patients
      who have an extended rapid virological response. Boceprevir is associated with an
      increased incidence of anaemia and dysgeusia and telaprevir is associated with an
      increased incidence of rash and anaemia. The emergence of RAVs was associated
      with an increased risk of virological failure in clinical studies. Although these
      new drugs bring significant promise, it remains unclear if all genotype 1
      patients will need triple therapy. Here, we review some of the complexities
      uncovered and controversies highlighted by the introduction of HCV protease
      inhibitors.

PMID- 22155902
TI  - Narasin, a novel antiviral compound that blocks dengue virus protein expression.
AB  - BACKGROUND: Dengue virus (DENV) is a mosquito-borne virus that causes a spectrum
      of human diseases ranging from mild dengue fever to dengue haemorrhagic fever and
      dengue shock syndrome in severe cases. Currently, there is no effective antiviral
      therapy or vaccine against DENV infection. METHODS: In order to identify
      potential antiviral agents against DENV, we performed high-throughput cell-based
      screening on a highly purified natural products library. Among the screening
      hits, selected compounds which displayed 50-75% inhibition against DENV2 were
      validated using secondary assays. Time-of-addition studies, dose-dependent
      assays, real time quantitative reverse transcriptase (RT)-PCR, Western blot and
      ultrastructural imaging were conducted in an attempt to elucidate the potential
      antiviral mechanisms of narasin. RESULTS: In this study, an ionophore, narasin
      was selected for detailed analysis due to its strong inhibitory profile against
      DENV infection with minimal cytotoxicity (50% cytotoxic concentration >1,000
      MUM). A dose-dependent study revealed narasin to have an 50% inhibitory
      concentration of less than 1 MUM against all four serotypes of DENV. Time-of
      addition studies of narasin-treated, DENV2-infected Huh-7 cells suggested narasin
      to be involved in inhibiting the post-entry stages of viral replication during
      DENV infection. Proteomic and ultrastructural analyses revealed the antiviral
      mechanism of narasin as likely to be associated with the disruption of viral
      protein synthesis. In addition, quantitative RT-PCR studies showed no differences
      in viral RNA levels between narasin-treated and control DENV2-infected cells.
      CONCLUSIONS: Narasin was identified and characterized as a novel agent that
      inhibits DENV replication in vitro through non-cytotoxic mechanisms, thus
      indicating its potential to be further developed as a therapeutic anti-DENV
      agent.

PMID- 22155903
TI  - The effectiveness of Carraguard, a vaginal microbicide, in protecting women
      against high-risk human papillomavirus infection.
AB  - BACKGROUND: A randomised, double-blind, placebo-controlled trial found the
      vaginal microbicide Carraguard unable to prevent HIV infection. A substudy
      assessed the association of genital high-risk human papillomavirus (HR-HPV) in
      women at study end with Carraguard use. METHODS: Participants received Carraguard
      gel or placebo plus condoms, and were instructed to use gel plus condoms during
      each act of vaginal intercourse. HR-HPV detection on cervical samples from 1,723
      women was by Digene Hybrid Capture 2 analysis. Poisson regression analysis
      assessed the prevalence of genital HR-HPV for individuals receiving Carraguard
      relative to individuals receiving placebo. RESULTS: In the Carraguard arm (n=875)
      the end trial unadjusted HR-HPV prevalence was 23.5% (95% CI 20.8-26.3) and 23.0%
      (95% CI 20.2-25.8) in placebo arm (n=843). Significant risk factors for HR-HPV
      infection were younger age, being single, an abnormal pap smear, multiple sexual
      partners and promiscuous behaviour without the use of a condom. There were 348
      compliant women (174 Carraguard, 174 placebo users), with relatively high
      adherence to gel use, who inserted 80% of their opened, returned applicators of
      test product with the proportion of applicator insertions to sex acts >30%. After
      adjusting for risk factors, these compliant Carraguard users were 0.62 as likely
      to be classified HR-HPV positive (95% CI 0.41-0.94) as compliant placebo users.
      CONCLUSIONS: The prevalence of HR-HPV infection was lower in compliant Carraguard
      users than compliant placebo users. To our knowledge, this is the first report
      showing a negative association of HPV infection with a vaginal microbicide.

PMID- 22155904
TI  - Valganciclovir prophylaxis against cytomegalovirus impairs lymphocyte
      proliferation and activation in renal transplant recipients.
AB  - BACKGROUND: Antiviral prophylaxis against cytomegalovirus has been associated
      with reduced risk of allograft rejection and improved allograft survival after
      renal transplantation. This phenomenon might not be fully explained by preventing
      the indirect effects of cytomegalovirus. The effect of antiviral agents on
      lymphocyte function in patients treated with modern immunosuppression has not
      been studied to date. METHODS: Adult renal transplant recipients were assigned to
      3-month prophylaxis with either valganciclovir (900 mg once daily; n=19) or
      valacyclovir (2 g four times daily; n=17) as part of an ongoing randomized trial.
      Subsets of lymphocytes, lymphocyte proliferation and/or cytokine production after
      in vitro mitogen stimulation were evaluated at the end of prophylaxis and 1 month
      after withdrawal of antiviral drugs. RESULTS: Lymphocyte proliferation was
      significantly decreased both after phytohemagglutinine (25% +/-15% versus 32% +/
      18%; P=0.025) and concanavalin A stimulation (17% +/-9% versus 25% +/-16%;
      P=0.011) during valganciclovir, but not valacyclovir therapy. Moreover, a lower
      activated T-cell count (CD3(+)HLA-DR(+) cells) was noted in valganciclovir
      treated patients (13% +/-10% versus 17% +/-12% of total CD3(+) T-cells; P=0.005).
      CONCLUSIONS: Valganciclovir suppresses lymphocyte proliferation and activation in
      patients after renal transplantation.

PMID- 22155905
TI  - Ribavirin and interferon alter MMP-9 abundance in vitro and in HIV-HCV-coinfected
      patients.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and their endogenous tissue
      inhibitors (TIMPs) are central to tissue remodelling during HIV-HCV infection.
      Here, we assess the potential for antiviral therapy to modulate MMP abundance in
      THP-1 monocyte/macrophages and LX-2 hepatic stellate cells, and in a coinfected
      patient cohort. METHODS: THP-1 and LX-2 cells were treated with ribavirin
      (RBV)/interferon-alpha (IFN-alpha) and select HIV antivirals. Venous blood was
      reserved from HIV-HCV-coinfected patients, HIV- and HCV-monoinfected patients,
      and healthy controls, with the HIV-HCV cohort being sampled again at day 3 and 14
      subsequent to the start of combination therapy with RBV/pegylated IFN-alpha.
      Samples were subjected to gelatin zymography, real-time RT-PCR and/or ELISA,
      where appropriate. RESULTS: RBV/IFN-alpha decreased MMP-9 activity, and increased
      MMP-9 mRNA and protein expression in THP-1 cells, but not in LX-2 cells.
      Decreases in MMP-9 activity were mediated by IFN-alpha, which also attenuated RBV
      induction of MMP-9 activity and protein expression in THP-1 cells. Saquinavir and
      lopinavir, HIV protease inhibitors, reduced MMP-9 activity in THP-1 and LX-2
      cells, respectively. Plasma MMP-9 activity and expression was higher in HIV-HCV
      and HIV patients compared with HCV patients and healthy controls. MMP-2 and TIMP
      2 levels were similar in all groups. RBV/pegylated IFN-alpha decreased plasma MMP
      9 abundance in HIV-HCV patients. CONCLUSIONS: These data demonstrate that
      RBV/pegylated IFN-alpha reduce plasma MMP-9 abundance in vivo and may reduce its
      activity in vitro through immune cells, such as monocyte/macrophages, rather than
      hepatic stellate cells. The results of this study indicate that such therapy may
      mediate tissue remodelling associated with HIV-HCV coinfection through effects on
      MMP-9.

PMID- 22155906
TI  - Prediction of off-treatment response to lamivudine by serum hepatitis B surface
      antigen quantification in hepatitis B e antigen-negative patients.
AB  - BACKGROUND: The timing of antiviral therapy cessation in hepatitis B e antigen
      (HBeAg)-negative patients is controversial. Here, we aimed to investigate the
      role of HBV DNA and hepatitis B surface antigen (HBsAg) monitoring to predict off
      treatment sustained response. METHODS: A total of 53 HBeAg-negative chronic
      hepatitis B patients who received lamivudine for 34 +/-23 (range 12-76) months
      and had lamivudine stopped for 47 +/-35 months were studied. Primary outcome was
      sustained response, defined as HBV DNA<=200 IU/ml, at 12 months post-treatment
      (SR-12). RESULTS: A total of 9 (17%) patients achieved SR-12. HBV DNA at
      baseline, month 6 and end of treatment had no association with SR-12. HBsAg
      levels tended to decrease more significantly during treatment among SR-12
      responders. At the end of treatment, both HBsAg <=2 log IU/ml and reduction by >1
      log from baseline had sensitivity, specificity, positive and negative predictive
      values for SR-12 of 78%, 96%, 78% and 96%, respectively. All 5 patients with
      HBsAg<=2 log IU/ml and reduction >1 log at the end of treatment achieved SR-12
      and all 40 patients with HBsAg>2 log IU/ml and reduction <=1 log did not have SR
      12. The cumulative probability of sustained response and HBsAg clearance at 5
      years among patients with HBsAg<=2 log IU/ml were 88% and 72%, respectively, that
      among patients with HBsAg reduction >1 log were 74% and 61%, respectively.
      CONCLUSIONS: Monitoring of HBsAg level can guide the timing of stopping
      lamivudine in HBeAg-negative chronic hepatitis B.

PMID- 22155907
TI  - In utero exposure to tenofovir disoproxil fumarate does not impair growth and
      bone health in HIV-uninfected children born to HIV-infected mothers.
AB  - BACKGROUND: Growth impairment and bone toxicity due to tenofovir disoproxil
      fumarate (TDF) fetal exposure has been described mainly in animals. We evaluated
      growth pattern and bone health in TDF-exposed HIV-uninfected children born to HIV
      infected mothers, defined as seroreverters (SR). METHODS: This was a multicentre
      observational cross-sectional cohort study enrolling 68 SR who were in utero
      exposed to an antiretroviral regimen including (TDF+) or not including (TDF-)
      tenofovir. Neonatal data and duration of antiretroviral exposure were recorded.
      At enrolment, anthropometric measures, tibial speed of sound (SOS) by
      quantitative ultrasound and several parameters of bone metabolism were assessed.
      RESULTS: Gestational age and median in utero antiretroviral exposure were similar
      in subjects exposed to TDF (n=33) and those non-exposed (n =35). Age at enrolment
      was comparable in the two groups (TDF-exposed range 11.8-76.2 months and TDF non
      exposed range 11.8-77.9 months). The incidence of low weight and length
      measurements (<10th percentiles) at birth was similar in TDF-exposed and TDF non
      exposed. Normal growth development was found in both groups of subjects at
      enrolment. The median (0.6; range -2.4-2.6) SOS z-score of TDF-exposed was
      similar to the median (0.8; range -2.2-4.4) SOS z-score of TDF non-exposed
      (Student's t=0.84; P=0.40). Parameters of bone metabolism were similar in the two
      groups. CONCLUSIONS: Exposure to TDF during pregnancy does not impair growth
      patterns, bone health and markers of bone metabolism in SR infants and young
      children born to HIV-infected women.

PMID- 22155908
TI  - Universal profiling of HIV-1 pol for genotypic study and resistance analysis
      across subtypes.
AB  - BACKGROUND: The increased use of anti-HIV-1 treatments in developing countries
      primarily infected by non-B subtypes necessitates development of novel tools to
      assess susceptibility and resistance. HIV-1 genomes are highly polymorphic and
      present challenges for the development of universal protocols capable of
      screening across subtypes. Currently available viral genotyping methods are
      useful for viral quantification, but are inadequate for sequence profiling or
      comprehensive mutation detection in the variable regions of HIV polymerase (pol).
      METHODS: A novel set of universal primers within pol, with consensus among a
      variety of HIV-1 subtypes, was developed. One-round amplification was performed
      by one-step reverse transcription PCR on 79 samples from HIV-1 subtypes. Using a
      second set of primers, the amplified fragment was sequenced and assembled to
      produce a profile database per sample. RESULTS: First-round amplification using
      universal primers generated a unique amplicon encompassing the major pol regions
      in all tested HIV-1 subtype samples. Sequence analysis of the amplified fragment
      not only confirmed the subtype of each HIV-1 isolate but also identified
      resistance mutations in the pol genes of HIV-1, including protease, reverse
      transcriptase, connection, RNase H, and integrase. Last, some of these primers
      were used to develop a viral load test using quantitative real time-PCR.
      CONCLUSIONS: A novel protocol was produced to effectively identify and
      simultaneously generate extensive sequence profiles of pol genes across HIV-1
      subtypes. This protocol allows for expeditious and cost-effective mutation
      detection, genotypic evaluation and viral load determination in multiple HIV-1
      subtypes.

PMID- 22155909
TI  - Paradoxical response to prophylactic Didox (N-3, 4 trihydroxybenzamide) treatment
      in murine cytomegalovirus-infected mice.
AB  - BACKGROUND: In this study, we investigated the effect of Didox (DX) on the
      pathogenicity of and host responses to murine cytomegalovirus (MCMV) infection.
      METHODS: In vitro efficacy of DX against MCMV was determined using plaque
      reduction assays. For in vivo studies, mice infected with a sublethal dose (10(4)
      PFU) of MCMV were treated daily with DX (200 mg/kg) using either a prophylactic
      or delayed protocol. At predetermined intervals, target organs were removed for
      histopathology. Cytokine transcription and viral load were performed using real
      time PCR. Serum cytokine levels were determined by ELISA, and T-cell markers by
      real-time PCR. RESULTS: DX (0.5-50 MUM) inhibited MCMV plaque formation in vitro.
      However, in vivo, prophylactic DX treatment did not decrease viral load and
      prolonged hepatic proinflammatory cytokine transcription at days 3 and 5 post
      infection, which corresponded with more severe histopathological changes observed
      in the liver. Significant CD8(+) T-cell marker suppression was seen, in
      accordance with DX-induced inhibition of lymphocyte proliferation observed in
      vitro. DX prolonged the recovery of MCMV-infected mice when given after infection
      was established. CONCLUSIONS: Despite promising MCMV inhibition in vitro, DX had
      no beneficial effect on MCMV disease in our model and paradoxically had adverse
      effects when administered prophylactically. The lack of correlation between in
      vitro activity and in vivo efficacy emphasizes the importance of selecting
      appropriate antiviral targets and of using animal models when testing new drugs.

PMID- 22155910
TI  - Pharmacokinetics and safety of a new paediatric fixed-dose combination of
      zidovudine/lamivudine/nevirapine in HIV-infected children.
AB  - BACKGROUND: Alternatives to the available stavudine-containing paediatric fixed
      dose combination (FDC) tablets are rapidly needed due to concerns regarding the
      cumulative toxicity of long-term stavudine exposure. We report the
      bioavailability and short-term safety of a novel paediatric FDC tablet of
      zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP; 30/15/28 mg) in HIV-infected
      children. METHODS: In this Phase I/II open-label pharmacokinetic study, 42
      children weighing 6-30 kg treated with NVP-based HAART for >=4 weeks were
      randomized to receive the FDC tablets (GPO-VIR Z30) or the liquid formulations.
      Dosing was weight-based. Intensive 12-h blood sampling was performed after 2
      weeks; subjects then crossed-over to the alternate formulation at equal doses and
      sampling repeated 2 weeks later. Pharmacokinetic parameters were determined by
      non-compartmental analysis. Buccal-swab samples were collected for cytochrome
      P450 (CYP)2B6 polymorphism analysis. RESULTS: With the FDC tablet, the geometric
      mean (90% CI) area under the curve (AUC) for ZDV, 3TC and NVP was 1.58 (1.49
      1.68), 7.78 (7.38-8.19) and 68.88 (62.13-76.36) MUg*h/ml, respectively. Rules for
      NVP therapeutic inadequacy were defined a priori, and despite lower NVP exposure
      with the tablet (P<0.001), the levels remained therapeutically adequate. ZDV AUC
      was similar between formulations. 3TC exposure was significantly higher with the
      tablet but comparable to historical data in adults and children taking branded
      tablets. While receiving the tablet, NVP AUC in children with CYP2B 516 GG (45%),
      GT (45%) and TT (10%) genotypes were 67.0, 74.5 and 106.4 MUg*h/ml, respectively
      (P=0.04). CONCLUSIONS: Disparities in drug exposure between formulations were
      observed; however, the FDC tablet delivered therapeutically adequate exposures of
      each drug and could well play an important role in simplifying antiretroviral
      treatment for children.

PMID- 22155911
TI  - Novel resistance-associated mutations of thymidine kinase and DNA polymerase
      genes of herpes simplex virus type 1 and type 2.
AB  - BACKGROUND: Studies to verify correlations between phenotypes and genotypes of
      herpes simplex virus (HSV) are an important tool to establish a database of
      resistance-associated mutations. METHODS: In this study, 32 acyclovir (ACV)
      resistant clinical HSV-1 and 4 ACV-resistant clinical HSV-2 isolates were
      examined in parallel by both phenotypic and genotypic resistance testing.
      Additionally, five non-viable HSV-1 strains and two non-viable HSV-2 strains with
      clinical resistance were included in genotypic resistance analysis. RESULTS: All
      ACV-resistant HSV isolates showed cross-resistance to brivudin and penciclovir,
      and were sensitive to foscarnet and cidofovir. Acyclovir resistance was assigned
      to frameshift and single non-synonymous mutations of the thymidine kinase (TK)
      gene in 32 out of 37 HSV-1 strains and in 4 out of 6 HSV-2 strains. In three HSV
      1 isolates, there were resistance-associated amino acid substitutions of the DNA
      polymerase (pol). Six substitutions in the TK and two in the DNA pol gene could
      not be attributed without doubt to either ACV resistance or natural gene
      polymorphism. Altogether, 10 resistance-related mutations in the TK and 1 in the
      DNA pol gene have not been reported previously. CONCLUSIONS: The novel non
      synonymous mutations found in this study enrich the knowledge about the genetic
      alterations of TK and DNA pol genes in ACV-resistant clinical HSV strains.
      Together with data from the literature, the findings justify the generation of a
      HSV database that contains resistance mutations associated with ACV resistance
      phenotype.

PMID- 22155912
TI  - IL28B CC-genotype association with HLA-DQB1*0301 allele increases the prediction
      of spontaneous HCV RNA clearance in thalassaemic HCV-infected patients.
AB  - BACKGROUND: A single nucleotide polymorphism (SNP), upstream of the IL28B gene
      has been recently associated with natural clearance of HCV. In a well
      characterized cohort of patients with thalassaemia major exposed to the risk of
      acquiring HCV infection by blood transfusions, we aimed to replicate this finding
      and to evaluate whether combining the IL28B genotype and HLA class II alleles
      allow viral clearance to be accurately predicted. METHODS: Of 168 patients, 130
      with complete clinical history were included in the analysis. According with
      their HCV antibodies status 13 were defined HCV resistant, and 117 infected.
      Infected patients were subdivided, giving 49 with self-limiting and 68 with
      ongoing infection. RESULTS: IL28B CC-genotype was observed in 32 patients with
      self-limiting and in 23 with ongoing infection (64% versus 34%; P=0.004). HLA
      DQB1*0301 allele was associated with viral clearance in 36 cases (73%; P<0.0001).
      Both DQB1*0301 and IL28B CC-genotype were found to be independent predictors of
      HCV clearance (OR=5.64, 95% CI 1.52-20.9 and OR=5.76, 95% CI 2.16-15.33,
      respectively). With the addition of DQB1*0301, the accuracy of the prediction
      increased from 63% to 69%. CONCLUSIONS: In addition to IL28B CC-genotype, HLA
      DQB1*0301 helps in predicting natural clearance of HCV after acute infection.

PMID- 22155913
TI  - Relative impact of ribavirin monitoring and HIV coinfection on sustained
      virological response in patients with chronic hepatitis C.
AB  - BACKGROUND: In chronic hepatitis C, higher ribavirin (RBV) concentrations are
      associated with sustained virological response (SVR); target concentration
      cutoffs have been proposed. As RBV displays interindividual variability,
      monitoring of RBV plasma levels appears relevant. The impact of RBV therapeutic
      drug monitoring (TDM(RBV)) on SVR has not been explored in current practice. Our
      study aimed to assess this impact. METHODS: Three patient groups were defined as
      RBV cutoffs achieved at week 12 (group A1), not achieved (group A2), and one
      without RBV concentration assessment (group B). A predictive model assessed the
      group impact on SVR in multivariate analysis, while adjusting for additional
      predictive factors. A specific evaluation of HIV-HCV-coinfected patients was
      performed. RESULTS: A total of 122 patients were included. In group A1 (n=30, HIV
      positive =18), SVR, relapse and non-response rates were 60%, 17% and 23%,
      respectively; in group A2 (n=32, HIV-positive =18), 25%, 19% and 56%,
      respectively; and in group B (n=60, HIV-positive =3), 52%, 33% and 15%,
      respectively (P=0.0004). The patient group was an independent predictor of SVR
      (P=0.01), along with baseline viral load and HCV genotype. HIV coinfection did
      not impede the SVR rate. The cutoffs were achieved in 62% and 28% (P=0.008) of
      patients, when TDM(RBV) was performed or not, respectively. CONCLUSIONS: The
      achievement of RBV cutoffs is a predictive factor of SVR independent of HIV
      coinfection. It makes it possible to reach high SVR rates, avoid relapse and
      obtain the same SVR rates in HIV-HCV-coinfected as in HCV-monoinfected patients.
      TDM(RBV) enables RBV concentration cutoffs to be reached more frequently and
      could thus be a useful tool to optimize hepatitis C treatment.

PMID- 22155914
TI  - Intravenous silibinin as 'rescue treatment' for on-treatment non-responders to
      pegylated interferon/ribavirin combination therapy.
AB  - BACKGROUND: Intravenous silibinin (ivSIL) is a potent antiviral agent against
      HCV. In vitro silibinin (SIL) inhibits viral replication, possibly by inhibiting
      HCV RNA polymerase. In this proof-of-concept study, ivSIL was tested in on
      treatment non-responders to full-dose of pegylated interferon-alpha2a/ribavirin
      (standard of care [SOC]). METHODS: A total of 27 treatment-naive patients with <2
      log drop in viral load after 12 weeks or still detectable HCV RNA after 24 weeks
      of SOC treatment (mean age 54.4 +/-6.8 years, male/female 19/8, HCV genotype 1
      n=19, 3a n=4 and 4 n=4, liver fibrosis F4 n=14, F3 n=5 and F2 n=3, and
      interleukin 28B polymorphism C/C n=1, T/C n=22 and T/T n=4) received additionally
      20 mg/kg/day SIL (Legalon-SIL((r)); Rottapharm-Madaus, Monza, Italy)
      intravenously for 14 or 21 days. Thereafter, pegylated interferon/ribavirin was
      continued. HCV RNA was quantified by TaqMan((r)) (Roche Diagnostics, Pleasanton,
      CA, USA). RESULTS: At the end of ivSIL treatment, 23/27 (85.1%) patients had
      undetectable HCV RNA. In one of the four remaining patients HCV RNA became
      undetectable 8 weeks after ivSIL on SOC. Five patients relapsed after ivSIL,
      three of them responded to repeated administration of ivSIL, but relapsed again.
      The best predictor of response was a low pre-ivSIL HCV RNA level. A total of 19
      patients reached one treatment end point (end of SOC treatment HCV RNA
      undetectable n=11 and non-response n=8); 8 patients were still on SOC (all HCV
      RNA-negative). All 11 patients with end-of-treatment response completed 24 weeks
      of follow-up; 7 patients remained HCV-RNA-negative and 4 relapsed. Except for a
      slight increase in bilirubin (mean +/-SD 0.98 +/-0.35 to 2.12 +/-0.99 mg/dl),
      treatment was well-tolerated. CONCLUSIONS: ivSIL is an effective 'rescue
      treatment' for on-treatment non-responders to full-dose of SOC.

PMID- 22155915
TI  - Abacavir, didanosine and tenofovir do not induce inflammatory, apoptotic or
      oxidative stress genes in coronary endothelial cells.
AB  - BACKGROUND: The use of abacavir and didanosine in HAART has been associated with
      an increased risk of myocardial infarction in HIV-infected patients. The aim of
      this study was to address the development of endothelial dysfunction in
      cultivated coronary artery endothelial cells (HCAECs) in response to abacavir,
      didanosine and tenofovir. We examined the impact of these drugs on the expression
      levels of the proinflammatory, oxidative stress and apoptosis regulating genes in
      HCAECs. METHODS: We tested gene and protein expression changes in HCAECs in
      response to abacavir, didanosine and tenofovir using quantitative real-time
      reverse transciptase PCR, FACS and ELISA. The assessed genes/proteins included
      the proinflammatory molecules VCAM-1, ICAM-1, MCP-1, RANTES and IL-6. In
      addition, we assessed the gene expression of the intracellular reactive oxygen
      producing NADPH oxidase subunit gp91(PHOX) and the apoptosis regulating molecules
      Bcl-2 and BAD. RESULTS: Exposure of HCAECs to abacavir, didanosine and tenofovir
      resulted in no statistically significant changes in any of the tested
      genes/proteins at any time point or at any concentration. CONCLUSIONS: We found
      no evidence that abacavir, didanosine or tenofovir had direct in vitro effects on
      coronary endothelial cell gene transcription and protein expression of the
      selected mediators. If abacavir or didanosine increase cardiovascular risk, it is
      likely not through the direct endothelial activation pathways tested in these
      experiments. However, further studies are needed to completely exclude the
      toxicity of abacavir or didanosine on endothelial cells.

PMID- 22155916
TI  - Open-label phase 1b pilot study to assess the antiviral efficacy of simvastatin
      combined with sertraline in chronic hepatitis C patients.
AB  - BACKGROUND: 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors inhibit
      HCV replication in vitro. The combination of sertraline and simvastatin has
      synergistic antiviral activity in vitro, but there are no prior in vivo studies.
      Our aims were to prospectively assess the antiviral efficacy and safety of this
      drug combination in chronic hepatitis C (CHC) patients. METHODS: A total of 15
      CHC adults (including 1 control subject) that were treatment-naive or prior
      partial responders/relapsers to standard-of-care therapy were enrolled at four
      centres (2 in Singapore and 2 in the US). Patients received simvastatin 40 mg
      once daily and sertraline 50 mg once daily for 7 days, and then 80 mg once daily
      and 100 mg once daily, respectively, for another 21 days with a 14-day follow-up.
      RESULTS: Of the 15 CHC patients, 13 completed the study. Subjects were mostly
      Caucasian (8/15), mean age 49.1 +/-9 years and the genotype distribution was
      1=10, 2=2 and 3=3. No subject discontinued dosing due to adverse events. Mean HCV
      RNA change from baseline was from -0.005 to -0.236 log(10) IU/ml across study
      intervals. Three subjects had transient >1 log(10) HCV RNA declines. No subject
      achieved >2 log(10) HCV RNA decline. CONCLUSIONS: The combination of sertraline
      and simvastatin is well-tolerated over the short-term, but has no significant
      antiviral or anti-inflammatory response in CHC patients. This may reflect in vivo
      differences in synergy between statin and/or selective serotonin reuptake
      inhibitors and incomplete inhibition of membrane protein prenylation with statin
      therapy.

PMID- 22155917
TI  - Surveillance of antiretroviral drug resistance mutations in untreated young
      children living in the Central African Republic.
AB  - BACKGROUND: A survey of drug resistance-associated mutations (DRMs) was conducted
      in 2009 among 77 vertically HIV-infected children not treated by antiretroviral
      drugs, followed up at the Complexe Pediatrique of Bangui, (Bangui, Central
      African Republic), a country where HIV mother-to-child transmission is prevented
      by the wide use of single-dose nevirapine in delivering mother and neonate.
      METHODS: Protease and reverse transcriptase sequencing was performed using the
      ViroSeq HIV-1 genotyping system, and DRMs were identified according to the 2009
      update surveillance of transmitted HIV-1 drug resistance. RESULTS: DRMs were
      detected in 6 out of 43 samples with interpretable genotypic resistance tests,
      leading to a 'moderate' DRM prevalence of 13.9% (95% CI 3.5-24.3). DRM to non
      nucleoside reverse transcriptase inhibitors were found in 5 samples (11.6% [95%
      CI, 2.0-21.2]) involving K103N, Y181C and G190A mutations. DRMs to nucleoside
      reverse transcriptase inhibitors was found in 1 sample (2.3% [95% CI 0.0-6.8]),
      with the K219Q mutation. No DRMs to protease inhibitors was detected.
      CONCLUSIONS: This survey predicts a moderate (between 5% and 15%) prevalence of
      DRMs in the Central African HIV-infected paediatric population of Bangui. These
      observations highlight the need to make an early diagnosis of the possibility of
      virological failure in Central African children receiving their first-line
      antiretroviral regimen.

PMID- 22155918
TI  - High prevalence of lipid abnormalities among antiretroviral-naive HIV-infected
      Asian children with mild-to-moderate immunosuppression.
AB  - BACKGROUND: Dyslipidaemia is a common complication among HIV-infected children
      after antiretroviral therapy (ART); however, HIV itself can cause abnormal lipid
      metabolism. There is limited information of lipid profiles among Asian HIV
      infected children naive to ART. METHODS: A total of 274 HIV-infected ART-naive
      Thai and Cambodian children aged 1-12 years with CD4% between 15% and 24% were
      included. Patients were fasted for >=4 h before blood was drawn. Abnormal lipid
      levels were defined as triglyceride (TG)>130 mg/dl, total cholesterol (TC)>200
      mg/dl, low-density lipoprotein (LDL)>130 mg/dl and high-density lipoprotein
      (HDL)<=40 mg/dl. RESULTS: The mean (+/-SD) was 76.6 (33.8) months for age and 
      1.3 (1.0) for weight Z-score. Mean (+/-SD) CD4% was 19.9 (4.8) % and HIV RNA was
      4.6 (0.6) log(10) copies/ml. The median (+/-SD) fasting time was 13.0 (2.7) h.
      Mean (+/-SD) for lipids were 116 (62) mg/dl for TG, 139 (29) mg/dl for TC, 73
      (29) mg/dl for LDL and 45 (19) mg/dl for HDL. Overall 63.9% had dyslipidaemia
      with hypertriglyceridaemia and hypo-HDL being the most common (28% and 45%,
      respectively), while 2% had hypercholesterolaemia or hyper-LDL. After adjusting
      for age, having HIV RNA>5 log(10) copies/ml was associated with hypo-HDL with ORs
      of 8.1 (95% CI 2.7-24.3). CONCLUSIONS: Up to two-thirds of ART-naive, HIV
      infected Asian children with mild-to-moderate immune suppression had
      dyslipidaemia. Low HDL was the most common and was associated with high HIV
      viraemia. The long-term consequence of low HDL deserves further investigation in
      children.

PMID- 22155919
TI  - Interaction of hydrogen with ZnO nanopowders--evidence of hydroxyl group
      formation.
AB  - There have been many investigations to reveal the nature of the hydrogen gas and
      ZnO nanopowder interaction at elevated temperatures, while at present no
      conclusive description of such an interaction has been confidently reported. In
      this work, we demonstrate that a hydroxyl group is formed during this
      interaction, depending on size and relative crystallinity of nanopowders. Our in
      situ Raman spectroscopy investigations show that the interaction directly affects
      the intensity of the Raman signal at 483 cm(-1), relative to the peak at 519 cm(
      1). Ex situ x-ray diffraction (XRD) and infrared spectroscopy also show extra
      peaks at 44 degrees  and 1618 cm(-1), respectively, after hydrogenation. These
      peaks were all identified as surface hydroxyl groups, which can be related to the
      formation of water on the ZnO nanopowder surfaces.

PMID- 22155920
TI  - Evaluation of 25-hydroxy vitamin D assay on the immunodiagnostic systems iSYS
      analyser.
AB  - BACKGROUND: We evaluated the recently released chemiluminescence assay for 25
      hydroxy vitamin D (25-OHD) on the Immunodiagnostic Systems iSYS (IDS-iSYS)
      automated analyser. METHODS: The IDS-iSYS comparison was performed using patient
      samples previously measured for 25-OHD by a validated liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method (n = 119) and an IDS enzyme immunoassy
      (IDS-EIA) method (n = 64). Limit of detection and limit of quantification were
      determined from a precision profile. Imprecision was assessed using quality
      control material and pooled serum. External QAP material (Vitamin D External
      Quality Assessment Scheme, UK) was analysed to establish inaccuracy. Linearity
      was assessed by two dilution studies. Cross-reactivity was determined by three
      serial dilution studies of patient samples with known 25-OHD(2) concentrations.
      RESULTS: The IDS-iSYS correlated well with both established methods (iSYS =
      1.03LC-MS/MS - 6.53, R(2) = 0.82 and iSYS = 1.07IDS-EIA - 1.61, R(2) = 0.86).
      Imprecision of the iSYS assay for IDS control material was 13.4% at 32 nmol/L,
      10% at 78 nmol/L, 9.4% at 161 nmol/L, and for the pooled material 9.3% at 72
      nmol/L and 5.6% at 158 nmol/L. The evaluation found the assay to be highly
      accurate (IDS-iSYS = 0.93ALTM + 3.79, R(2) = 0.94) and linear (obs(1) =
      0.93exp(1) - 5.05, R(2) = 0.99 (P = 0.256); and obs(2) = 0.97exp(2) + 6.07, R(2)
      = 0.97 (P = 0.654); ALTM, all-laboratory trimmed mean). Cross-reactivity studies
      demonstrated no significant difference to the calculated total 25-OHD as measured
      by LC-MS/MS. CONCLUSIONS: Even though the imprecision of the iSYS was found to be
      greater than that of the LC-MS/MS and EIA methods, the performance
      characteristics of the IDS-iSYS 25-OHD assay are suitable for routine diagnostic
      purposes on a high throughput automated analyser.

PMID- 22155922
TI  - Effect of freeze-thaw and refrigeration conditions on high-sensitivity troponin T
      concentrations.

PMID- 22155921
TI  - Clinical usefulness of blood metal measurements to assess the failure of metal-on
      metal hip implants.
AB  - In April 2010, a Medicines and Healthcare Products Regulatory Agency safety alert
      concerning all metal-on-metal (MOM) hip replacements recommended measuring
      chromium and cobalt concentrations when managing patients with painful
      prostheses. The need for this review is illustrated by the recent surge in
      requests for these blood tests from orthopaedic surgeons following this alert.
      The aim is to provide guidance to laboratories in assessing these requests and
      advising clinicians on interpretation. First, we summarize the basic terminology
      regarding the types of hip replacements, with emphasis on the MOM type. Second,
      we describe the clinical concerns over implant-derived wear debris in the local
      tissues and distant sites. Analytical aspects of the measurement of the relevant
      metal ions and what factors affect the levels measured are discussed. The
      application of inductively coupled plasma mass spectrometry techniques to the
      measurement of these metals is considered in detail. The biological effects of
      metal wear products are summarized with local toxicity and systemic biological
      effects considered, including carcinogenicity, genotoxicity and systemic
      toxicity. Clinical cases are used to illustrate pertinent points.

PMID- 22155923
TI  - Amorphous Ge15Te85: density functional, high-energy x-ray and neutron diffraction
      study.
AB  - The structure and electronic properties of amorphous Ge(15)Te(85) have been
      studied by combining density functional (DF) simulations with high-energy x-ray
      and neutron diffraction measurements. Three models with 560 atoms have been
      constructed using reverse Monte Carlo methods constrained to (1) agree with the
      experimental structure factors S(Q), and have (2) energies close to the DF
      minimum and (3) a semiconducting band structure. The best structure is based on
      the melt-quenched DF structure and has a small number of Ge-Ge bonds. It shows
      interlocking networks of Te and GeTe with a significant fraction (22-24%) of
      voids (cavities). Ge occurs with both tetrahedral and 3 + 3 defective octahedral
      configurations, and the coordination of Te is slightly higher than indicated by
      the '8 - N rule' (N is the number of valence electrons). The GeTe network
      includes clusters of ABAB squares (A = Ge, B = Te), and the bonding is
      characterized by the chemical bond orders.

PMID- 22155924
TI  - Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal
      differentiation.
AB  - Long noncoding RNAs (lncRNAs) are differentially expressed under both normal and
      pathological conditions, implying that they may play important biological
      functions. Here we examined the expression of lncRNAs during erythropoiesis and
      identified an erythroid-specific lncRNA with anti-apoptotic activity. Inhibition
      of this lncRNA blocks erythroid differentiation and promotes apoptosis.
      Conversely, ectopic expression of this lncRNA can inhibit apoptosis in mouse
      erythroid cells. This lncRNA represses expression of Pycard, a proapoptotic gene,
      explaining in part the inhibition of programmed cell death. These findings reveal
      a novel layer of regulation of cell differentiation and apoptosis by a lncRNA.

PMID- 22155925
TI  - The role of nuclear lamin B1 in cell proliferation and senescence.
AB  - Nuclear lamin B1 (LB1) is a major structural component of the nucleus that
      appears to be involved in the regulation of many nuclear functions. The results
      of this study demonstrate that LB1 expression in WI-38 cells decreases during
      cellular senescence. Premature senescence induced by oncogenic Ras also decreases
      LB1 expression through a retinoblastoma protein (pRb)-dependent mechanism.
      Silencing the expression of LB1 slows cell proliferation and induces premature
      senescence in WI-38 cells. The effects of LB1 silencing on proliferation require
      the activation of p53, but not pRb. However, the induction of premature
      senescence requires both p53 and pRb. The proliferation defects induced by
      silencing LB1 are accompanied by a p53-dependent reduction in mitochondrial
      reactive oxygen species (ROS), which can be rescued by growth under hypoxic
      conditions. In contrast to the effects of LB1 silencing, overexpression of LB1
      increases the proliferation rate and delays the onset of senescence of WI-38
      cells. This overexpression eventually leads to cell cycle arrest at the G1/S
      boundary. These results demonstrate the importance of LB1 in regulating the
      proliferation and senescence of human diploid cells through a ROS signaling
      pathway.

PMID- 22155926
TI  - Thermally induced morphology evolution of pit-patterned Si substrate and its
      effect on nucleation properties of Ge dots.
AB  - We demonstrate the effect of the pre-growth heat treatment process on the
      nucleation properties of Ge dots grown on pit-patterned Si(001) substrates. The
      prefabricated 200 nm diameter pits inherently evolve into truncated inverted
      pyramids (TIPs) with (110) base edges and a 7 degrees -9 degrees  sidewall slope
      during heat treatment; this morphology transformation is robust against
      variations in shape and orientation of the pit patterns. Uniform Ge dots with an
      areal density of 4 * 10(9) cm(-2) were obtained on the Si substrates having TIPs.
      Each TIP contains four aligned Ge dots locating symmetrically with respect to
      (110). These dots exhibit an elliptical dome shape with major axis oriented along
      (100). The nucleation position, shape and spatial orientation of these Ge dots
      coincide with the calculated surface chemical potential distribution of the TIP.

PMID- 22155927
TI  - Adaptive SLICE method: an enhanced method to determine nonlinear dynamic
      respiratory system mechanics.
AB  - The objective of this paper is to introduce and evaluate the adaptive SLICE
      method (ASM) for continuous determination of intratidal nonlinear dynamic
      compliance and resistance. The tidal volume is subdivided into a series of volume
      intervals called slices. For each slice, one compliance and one resistance are
      calculated by applying a least-squares-fit method. The volume window (width)
      covered by each slice is determined based on the confidence interval of the
      parameter estimation. The method was compared to the original SLICE method and
      evaluated using simulation and animal data. The ASM was also challenged with
      separate analysis of dynamic compliance during inspiration. If the signal-to
      noise ratio (SNR) in the respiratory data decreased from +infinity to 10 dB, the
      relative errors of compliance increased from 0.1% to 22% for the ASM and from
      0.2% to 227% for the SLICE method. Fewer differences were found in resistance.
      When the SNR was larger than 40 dB, the ASM delivered over 40 parameter estimates
      (42.2 +/- 1.3). When analyzing the compliance during inspiration separately, the
      estimates calculated with the ASM were more stable. The adaptive determination of
      slice bounds results in consistent and reliable parameter values. Online analysis
      of nonlinear respiratory mechanics will profit from such an adaptive selection of
      interval size.

PMID- 22155928
TI  - Incidences and range of spontaneous findings in the lymphoid and haemopoietic
      system of control Charles River CD-1 mice (Crl: CD-1(ICR) BR) used in chronic
      toxicity studies.
AB  - The authors performed a retrospective study to determine the incidences and range
      of spontaneous pathology findings in the lymphoid and haemopoietic systems of
      control Charles River CD-1 mice (Crl: CD-1(ICR) BR). Data was collected from
      2,560 mice from control dose groups (104-week and 80-week carcinogenicity
      studies; 13-week studies), from regulatory studies evaluated at the authors'
      laboratory between 2005 and 2010. Lesions of the lymphoid and hematopoietic
      systems were uncommon in 13-week studies but were of high incidence in the
      carcinogenicity studies (80- or 104-week duration). The most common finding
      overall was lymphoid hyperplasia within the spleen, thymus, and lymph nodes. The
      finding of benign lymphoid hyperplasia of the thymus is unusual in other mouse
      strains. The most common cause of death in the carcinogenicity studies was
      lymphoma. It is hoped that the results presented here will provide a useful
      database of incidental pathology findings in CD-1 mice on carcinogenicity
      studies.

PMID- 22155929
TI  - Longitudinal and transversal propagation of excitation along the tubular system
      of rat fast-twitch muscle fibres studied by high speed confocal microscopy.
AB  - Mammalian skeletal muscle fibres possess a tubular (t-) system that consists of
      regularly spaced transverse elements which are also connected in the longitudinal
      direction. This tubular network provides a pathway for the propagation of action
      potentials (APs) both radially and longitudinally within the fibre, but little is
      known about the actual radial and longitudinal AP conduction velocities along the
      tubular network in mammalian skeletal muscle fibres. The aim of this study was to
      track AP propagation within the t-system network of fast-twitch rat muscle fibres
      with high spatio-temporal resolution when the t-system was isolated from the
      surface membrane. For this we used high speed confocal imaging of AP-induced
      Ca(2+) release in contraction-suppressed mechanically skinned fast-twitch fibres
      where the t-system can be electrically excited in the absence of the surface
      membrane. Supramaximal field pulses normally elicited a synchronous AP-induced
      release of Ca(2+) along one side of the fibre axis which propagated uniformly
      across the fibre. In some cases up to 80 or more adjacent transverse tubules
      failed to be excited by the field pulse, while adjacent areas responded with
      normal Ca(2+) release. In these cases a continuous front of Ca(2+) release with
      an angle to the scanning line was observed due to APs propagating longitudinally.
      From these observations the radial/transversal and longitudinal AP conduction
      velocities along the tubular network deeper in the fibre under our conditions (19
      +/- 1 degrees C) ranged between 8 and 11 MUm ms(-1) and 5 to 9 MUm ms(-1),
      respectively, using different methods of estimation. The longitudinal propagation
      of APs appeared to be markedly faster closer to the edge of the fibre, in
      agreement with the presence of dense longitudinal connections immediately below
      the surface of the fibre and more sparse connections at deeper planes within the
      fibre. During long trains of closely spaced field pulses the AP-elicited Ca(2+)
      releases became non-synchronous along the fibre axis. This is most likely caused
      by local tubular K(+) accumulation that produces local depolarization and local
      slowing of AP propagation. Longitudinally propagating APs may reduce such
      inhomogeneities by exciting areas of delayed AP onset. Clearly, the longitudinal
      tubular pathways within the fibre for excitation are used as a safety mechanism
      in situations where a local depolarization obstructs immediate excitation from
      the sarcolemma. Results obtained from this study also provide an explanation for
      the pattern of contractures observed in rippling muscle disease.

PMID- 22155930
TI  - Pro- and anti-angiogenic factors in human skeletal muscle in response to acute
      exercise and training.
AB  - This study examined the effect of acute exercise and 4 weeks of aerobic training
      on skeletal muscle gene and protein expression of pro- and anti-angiogenic
      factors in 14 young male subjects. Training consisted of 60 min of cycling (~60%
      of ), 3 times/week. Biopsies were obtained from vastus lateralis muscle before
      and after training. Muscle interstitial fluid was collected during cycling at
      weeks 0 and 4. Training increased (P < 0.05) the capillary: fibre ratio and
      capillary density by 23% and 12%, respectively. The concentration of interstitial
      vascular endothelial growth factor (VEGF) in response to acute exercise increased
      similarly (>6-fold; P < 0.05) before and after training. Resting protein levels
      of soluble VEGF receptor-1 in interstitial fluid, and of VEGF, thrombospondin-1
      (TSP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP1) in muscle were
      unaffected by training, whereas endothelial nitric oxide synthase protein levels
      in muscle increased by 50% (P < 0.05). Before and after training, acute exercise
      induced a similar increase (P < 0.05) in the mRNA level of angiopoietin 2, matrix
      metalloproteinase 9 and TSP-1. After training, TIMP1 mRNA content increased with
      exercise (P < 0.05). In conclusion, acute exercise induced a similar increase in
      the gene-expression of both pro- and anti-angiogenic factors in untrained and
      trained muscle. We propose that the increase in anti-angiogenic factors with
      exercise is important for modulation of angiogenesis. The lack of effect of
      training on basal muscle VEGF protein levels and VEGF secretion during exercise
      suggests that increased VEGF levels are not a prerequisite for exercise-induced
      capillary growth in healthy muscle.

PMID- 22155931
TI  - Fast reduction of peripheral blood endothelial progenitor cells in healthy humans
      exposed to acute systemic hypoxia.
AB  - There are hints that hypoxia exposure may affect the number of circulating
      endothelial progenitor cells (EPCs) in humans. To test this hypothesis, the
      concentration of EPCs was determined by flow cytometry in the peripheral blood of
      10 young healthy adults before (0 h), at different times (0.5 h, 1 h, 2 h and 4
      h) during a 4 h normobaric hypoxic breathing simulating 4100 m altitude, and in
      the following recovery breathing room air. Results were interpreted mainly on the
      basis of the changes in surface expression of CXC chemokine receptor-4 (CXCR-4, a
      chemokine receptor essential for EPC migration and homing) and the percentage of
      apoptotic cells, the plasmatic levels of markers of oxidative stress induced by
      hypoxic breathing. Compared to 0 h, the concentration of EPCs, identified as
      either CD45(dim)/CD34(+)/KDR(+) or CD45(dim)/CD34(+)/KDR(+)/CD133(+) cells,
      decreased from 337 +/- 83 ml(-1) (mean +/- SEM) to 223 +/- 52 ml(-1) (0.5 h; P <
      0.005) and 100 +/- 37 ml(-1) (4 h; P < 0.005), and from 216 +/- 91 to 161 +/- 50
      ml(-1) (0.5 h; P < 0.05) and 45 +/- 23 ml(-1) (4 h; P < 0.005), respectively.
      Upon return to normoxia, their concentration increased slowly, and after 4 h was
      still lower than at 0 h (P < 0.05). During hypoxia, CXCR-4 expression and
      plasmatic stromal derived cell factor-1 (SDF-1) increased abruptly (0.5 h: +126%
      and +13%, respectively; P < 0.05), suggesting cell marginalization as a possible
      cause of the rapid hypoxia-induced EPC reduction. Moreover, hypoxia exposure
      induced an increase in EPC apoptosis and markers of oxidative stress, which was
      significantly evident only starting from 2 h and 4 h after hypoxia offset,
      respectively, suggesting that EPC apoptosis may contribute to the later phase of
      hypoxia-induced EPC reduction. Overall, these observations may provide new
      insights into the understanding of the mechanisms operated by EPCs to maintain
      endothelial homeostasis.

PMID- 22155932
TI  - Prenatal stress alters hippocampal synaptic plasticity in young rat offspring
      through preventing the proteolytic conversion of pro-brain-derived neurotrophic
      factor (BDNF) to mature BDNF.
AB  - Prenatal stress (PS) has been associated with a higher risk of development of
      various neurological and psychiatric disorders later in life, but the underlying
      mechanisms are not yet fully understood. Here, using a chronic prenatal restraint
      stress model where the rat dams were immobilized for 45 min three times per day
      during the last week of pregnancy, we explored the long-lasting effects of PS on
      hippocampal synaptic plasticity in the offspring of both sexes. We found that PS
      switched the direction of synaptic plasticity in hippocampal CA1 region,
      favouring low-frequency stimulation-induced long-term depression (LTD) and
      opposing the induction of long-term potentiation (LTP) by high-frequency
      stimulation in young (5-week-old) rat offspring, but these changes disappeared at
      adult age (8 weeks old). Fostering of PS offspring to control dams did not alter
      the effects of PS on LTP and LTD. In addition, PS-induced changes in LTP and LTD
      induction were correlated with increasing endogenous pro-brain-derived
      neurotrophic factor (pro-BDNF) and decreasing of the mature form of BDNF (mBDNF)
      levels. Furthermore, PS resulted in a significant decrease in the activity and
      expression of tissue plasminogen activator (tPA), a key serine protease involved
      in the extracellular conversion of pro-BDNF to mBDNF. No significant differences
      were observed between the sexes for the effects of PS on hippocampal synaptic
      plasticity, the levels of pro-BDNF and mBDNF, and tPA expression. These results
      suggest that PS downregulates tPA levels within the hippocampus, inhibiting the
      proteolytic conversion of pro-BDNF to mBDNF, thereby leading to long-lasting
      alterations of the properties of synaptic plasticity.

PMID- 22155933
TI  - Pivotal role of mitochondrial Na+-Ca2+ exchange in antigen receptor mediated Ca2+
      signalling in DT40 and A20 B lymphocytes.
AB  - Cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) increases upon activation of
      antigen-receptor in lymphocytes. Mitochondria have been suggested to regulate the
      [Ca(2+)](i) response, but the molecular mechanisms and the roles are poorly
      understood. To clarify them, we carried out a combination study of mathematical
      simulations and knockout or knockdown of NCLX, a gene candidate for the
      mitochondrial Na(+)-Ca(2+) exchanger (NCX(mit)), in B lymphocytes. A mathematical
      model of Ca(2+) dynamics in B lymphocytes demonstrated that NCX(mit) inhibition
      reduces basal Ca(2+) content of endoplasmic reticulum (ER) and suppresses B-cell
      antigen receptor (BCR)-mediated [Ca(2+)](i) rise. The predictions were validated
      in DT40 B lymphocytes of heterozygous NCLX knockout (NCLX(+/-)). In NCLX(+/-)
      cells, mitochondrial Ca(2+) efflux via NCX(mit) was strongly decelerated,
      suggesting NCLX is a gene responsible for NCX(mit) in B lymphocytes. Consistent
      with the predictions, ER Ca(2+) content declined and [Ca(2+)](i) hardly rose upon
      BCR activation in NCLX(+/-) cells. ER Ca(2+) uptake was reduced to ~58% of the
      wild-type (WT), while it was comparable to WT when mitochondrial respiration was
      disturbed. Essentially the same results were obtained by a pharmacological
      inhibition or knockdown of NCLX by siRNA in A20 B lymphocytes. Unexpectedly, ER
      Ca(2+) leak was augmented and co-localization of mitochondria with ER was lower
      in NCLX(+/-) and NCLX silenced cells. Taken together, we concluded that NCLX is a
      key Ca(2+) provider to ER, and that NCLX-mediated Ca(2+) recycling between
      mitochondria and ER is pivotal in B cell responses to antigen.

PMID- 22155934
TI  - Systemic cholecystokinin amplifies vago-vagal reflex responses recorded in vagal
      motor neurones.
AB  - Cholecystokinin (CCK) is a potent regulator of visceral functions as a
      consequence of its actions on vago-vagal reflex circuit elements. This paper
      addresses three current controversies regarding the role of CCK to control
      gastric function via vago-vagal reflexes. Specifically: (a) whether CNS vs.
      peripheral (vagal afferent) receptors are dominant, (b) whether the long (58) vs.
      short (8) isoform is more potent and (c) whether nutritional status impacts the
      gain or even the direction of vago-vagal reflexes. Our in vivo recordings of
      physiologically identified gastric vagal motor neurones (gastric-DMN) involved in
      the gastric accommodation reflex (GAR) show unequivocally that: (a) receptors in
      the coeliac-portal circulation are more sensitive in amplifying gastric vagal
      reflexes; (b) in the periphery, CCK8 is more potent than CCK58; and (c) the
      nutritional status has a marginal effect on gastric reflex control. While the GAR
      reflex is more sensitive in the fasted rat, CCK amplifies this sensitivity. Thus,
      our results are in stark contrast to recent reports which have suggested that
      vago-vagal reflexes are inverted by the metabolic status of the animal and that
      this inversion could be mediated by CCK within the CNS.

PMID- 22155935
TI  - M channel enhancers and physiological M channel block.
AB  - M-type (Kv7, KCNQ) K(+) channels control the resting membrane potential of many
      neurons, including peripheral nociceptive sensory neurons. Several M channel
      enhancers were suggested as prospective analgesics, and targeting M channels
      specifically in peripheral nociceptors is a plausible strategy for peripheral
      analgesia. However, receptor-induced inhibition of M channels in nociceptors is
      often observed in inflammation and may contribute to inflammatory pain. Such
      inhibition is predominantly mediated by phospholipase C. We investigated four M
      channel enhancers (retigabine, flupirtine, zinc pyrithione and H(2)O(2)) for
      their ability to overcome M channel inhibition via two phospholipase C-mediated
      mechanisms, namely depletion of membrane phosphatidylinositol 4,5-bisphosphate
      (PIP(2)) and a rise in intracellular Ca(2+) (an action mediated by calmodulin).
      Data from overexpressed Kv7.2/Kv7.3 heteromers and native M currents in dorsal
      root ganglion neurons suggest the following conclusions. (i) All enhancers had a
      dual effect on M channel activity, a negative shift in voltage dependence and an
      increase of the maximal current at saturating voltages. The enhancers differed in
      their efficacy to produce these effects. (ii) Both PIP(2) depletion and
      Ca(2+)/calmodulin strongly reduced the M current amplitude; however, at voltages
      near the threshold for M channel activation (-60 mV) all enhancers were able to
      restore M channel activity to a control level or above, while at saturating
      voltages the effects were more variable. (iii) Receptor-mediated inhibition of M
      current in nociceptive dorsal root ganglion neurons did not reduce the efficacy
      of retigabine or flupirtine to hyperpolarize the resting membrane potential. In
      conclusion, we show that all four M channel enhancers tested could overcome both
      PIP(2) and Ca(2+)-calmodulin-induced inhibition of Kv7.2/7.3 at voltages close to
      the threshold for action potential firing (-60 mV) but generally had reduced
      efficacy at a saturating voltage (0 mV). We suggest that the efficacy of an M
      channel enhancer to shift the voltage dependence of activation may be most
      important for rescuing M channel function in sensory neurons innervating inflamed
      tissue.

PMID- 22155936
TI  - Characterization of dynamic interactions between cardiovascular signals by time
      frequency coherence.
AB  - An assessment of the dynamic interactions between cardiovascular signals can
      provide valuable information to improve the understanding of cardiovascular
      control. In this study, two methodologies for the characterization of time
      frequency (TF) coherence between cardiovascular signals are described. The
      methodologies are based on the smoothed pseudo-Wigner-Ville distribution (SPWVD)
      and multitaper spectrogram (MTSP), and include the automatic assessment of the
      significance level of coherence estimates. The capability to correctly localize
      TF regions, where signals are locally coupled, is assessed using computer
      generated data, and data from healthy volunteers. The SPWVD allows for the
      localization of these regions with higher accuracy (AC   > 96.9% for SNR  >=  5
      dB) than the MTSP (AC  > 84.4% for SNR   >= 5 dB). In 14 healthy subjects, TF
      coherence analysis was used to describe the changes, which a tilt table test
      provokes in the cardiovascular control. Orthostatic stress provoked an increase
      in the coupling between R-R variability (RRV) and systolic arterial pressure
      variability; it did not provoke any significant changes in the coupling between
      RRV and respiration. In HF band, it decreased the strength of the coupling
      between RRV and pulse interval variability estimated from arterial pressure
      signal.

PMID- 22155937
TI  - Noncontact tremor characterization using low-power wideband radar technology.
AB  - Continuous monitoring and analysis of tremor is important for the diagnosis and
      establishment of treatments in many neurological disorders. This paper describes
      noncontact assessment of tremor characteristics obtained by an experimental new
      ultrawideband (UWB) system. The system is based on transmission of a wideband
      electromagnetic signal with extremely low power, and analysis of the received
      signal, which is composed of many propagation paths reflected from the patient
      and its surroundings. A description of the physical principles behind the
      technology, a criterion, and efficient algorithms to assess tremor
      characteristics from the bulk UWB measurements are given. A feasibility test for
      the technology was conducted using a UWB system prototype, an arm model that
      mimics tremor, and a reference video system. The set of UWB system frequencies
      and amplitudes estimations were highly correlated with the video system
      estimations with an average error in the scale of 0.1 Hz and 1 mm for the
      frequency and amplitude estimations, respectively. The new UWB-based system does
      not require attaching active markers or inertial sensors to the body, can give
      displacement information and kinematic features from multiple body parts, is not
      limited by the range captured by the optical lens, has high indoor volume
      coverage as it can penetrate through walls, and does not require calibration to
      obtain amplitude estimations.

PMID- 22155938
TI  - Unidentified Chronic Fatigue Syndrome/myalgic encephalomyelitis (CFS/ME) is a
      major cause of school absence: surveillance outcomes from school-based clinics.
AB  - Objective To investigate the feasibility of conducting clinics for chronic
      fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in schools.  Design School
      based clinical project.  Participants Children aged 11-16 years were enrolled in
      three state secondary schools in England.  Main outcome measures Number of
      children newly diagnosed as having CFS/ME.  Methods Attendance officers
      identified children missing >=20% of school in a 6-week term without a known
      cause, excluding those with a single episode off school, a known medical illness
      explaining the absence or known to be truanting. Children with fatigue were
      referred to a specialist CFS/ME service for further assessment. The authors
      compared children with CFS/ME identified through school-based clinics with those
      referred via health services. Outcomes of CFS/ME were evaluated at 6 weeks and 6
      months.  Results 461 of the 2855 enrolled children had missed >=20% school over a
      6-week period. In 315, of whom three had CFS/ME, the reason for absence was
      known. 112 of the 146 children with unexplained absence attended clinical review
      at school; two had been previously diagnosed as having CFS/ME and 42 were
      referred on to a specialist clinic, where 23 were newly diagnosed as having
      CFS/ME. Therefore, 28 of the 2855 (1.0%) children had CFS/ME. Children with
      CFS/ME identified through surveillance had been ill for an amount of time
      comparable to those referred via health services but had less fatigue (mean
      difference 4.4, 95% CI 2.2 to 6.6), less disability (mean difference -5.7, 95% CI
      -7.9 to -3.5) and fewer symptoms (mean difference 1.86, 95% CI 0.8 to 2.93). Of
      19 children followed up, six had fully recovered at 6 weeks and a further six at
      6 months.  Conclusions Chronic fatigue is an important cause of unexplained
      absence from school. Children diagnosed through school-based clinics are less
      severely affected than those referred to specialist services and appear to make
      rapid progress when they access treatment.

PMID- 22155939
TI  - Stress-induced cortisol level elevations are associated with reduced negative
      affect after stress: indications for a mood-buffering cortisol effect.
AB  - OBJECTIVE: Stress is associated with increased negative affect and activation of
      the sympathetic nervous system and of the hypothalamic-pituitary-adrenal axis.
      However, the relationship between these stress systems and negative affect is
      incompletely understood. We therefore investigated positive and negative affects
      in relationship with salivary cortisol and salivary alpha-amylase (sAA) levels in
      a large sample of participants exposed to a psychosocial stressor or a control
      condition. METHODS: Cortisol and sAA levels from five studies with a total sample
      size of 232 participants were reanalyzed using hierarchical linear modeling. In
      these studies, we measured affective responses to the Trier Social Stress Test
      (TSST) and its control condition (placebo TSST) with the Positive and Negative
      Affect Schedule. RESULTS: An inverse relationship between cortisol and negative
      affect was observed across all participants (beta(06) = -0.13, p = .002). Higher
      level of negative affect was associated with lower mean cortisol levels 10
      minutes after the TSST or the control condition. When the two conditions were
      tested separately, the effect was significant in the stress condition (beta(06) =
      -0.05, p = .02) but not in the control condition (beta(06) = -0.0008, p > .05).
      In contrast to the results for cortisol, a positive relationship was found
      between sAA and negative affect within the stress condition (beta(06) = 0.10, p =
      .005). CONCLUSIONS: The present findings suggest that cortisol is associated with
      an attenuated negative emotional arousal in response to acute stress, whereas sAA
      levels seem to reflect the degree of negative emotional arousal. Together with
      previous pharmacological studies, these data seem to support the hypothesis of
      mood-buffering effects of cortisol.

PMID- 22155940
TI  - Type D personality, self-efficacy, and medication adherence following an acute
      coronary syndrome.
AB  - OBJECTIVE: To assess the relationship among Type D personality, self-efficacy,
      and medication adherence in patients with coronary heart disease. METHODS: The
      study design was prospective and observational. Type D personality, self-efficacy
      for illness management behaviors, and medication adherence were measured 3 weeks
      after hospitalization for acute coronary syndrome in 165 patients (mean [standard
      deviation] age = 61.62 [10.61] years, 16% women). Self-reported medication
      adherence was measured 6 months later in 118 of these patients. Multiple linear
      regression and mediation analyses were used to address the study research
      questions. RESULTS: Using the original categorical classification, 30% of
      patients with acute coronary syndrome were classified as having Type D
      personality. Categorically defined patients with Type D personality had
      significantly poorer medication adherence at 6 months (r = -0.29, p < .01).
      Negative affectivity (NA; r = -0.25, p = .01) and social inhibition (r = -0.19, p
      = .04), the components of Type D personality, were associated with medication
      adherence 6 months after discharge in bivariate analyses. There was no evidence
      for the interaction of NA and social inhibition, that is, Type D personality, in
      the prediction of medication adherence 6 months after discharge in multivariate
      analysis. The observed association between NA and medication adherence 6 months
      after discharge could be partly explained by indirect effects through self
      efficacy in mediation analysis (coefficient = -0.012; 95% bias-corrected and
      accelerated confidence interval = -0.036 to -0.001). CONCLUSIONS: The present
      data suggest the primacy of NA over the Type D personality construct in
      predicting medication adherence. Lower levels of self-efficacy may be a mediator
      between higher levels of NA and poor adherence to medication in patients with
      coronary heart disease.

PMID- 22155941
TI  - Physiologic dysfunction scores and cognitive function test performance in U.S.
      adults.
AB  - OBJECTIVE: To investigate the relationship between a measure of cumulative
      physiologic dysfunction and specific domains of cognitive function. METHODS: We
      examined a summary score measuring physiologic dysfunction, a multisystem measure
      of the body's ability to effectively adapt to physical and psychological demands,
      in relation to cognitive function deficits in a population of 4511 adults aged 20
      to 59 who participated in the Third National Health and Nutrition Examination
      Survey (1988-1994). Measures of cognitive function comprised three domains:
      working memory, visuomotor speed, and perceptual-motor speed. "Physiologic
      dysfunction" scores summarizing measures of cardiovascular, immunologic, kidney,
      and liver functions were explored. We used multiple linear regression models to
      estimate associations between cognitive function measures and physiologic
      dysfunction scores, adjusting for socioeconomic factors, test conditions, and
      self-reported health factors. RESULTS: We noted a dose-response relationship
      between physiologic dysfunction and working memory (coefficient = 0.207, 95%
      confidence interval = 0.066-0.348, p < .0001), which persisted after adjustment
      for all covariates (p = .03). We did not observe any significant relationships
      between dysfunction scores and visuomotor (p = .37) or perceptual-motor ability
      (p = .33). CONCLUSIONS: Our findings suggest that multisystem physiologic
      dysfunction is associated with working memory. Future longitudinal studies are
      needed to clarify the underlying mechanisms and explore the persistency of this
      association into later life. We suggest that such studies should incorporate
      physiologic data, neuroendocrine parameters, and a wide range of specific
      cognitive domains.

PMID- 22155942
TI  - The effects of urban bus driving on blood pressure and musculoskeletal problems:
      a quasi-experimental study.
AB  - OBJECTIVE: Work settings with high levels of stress are consistently associated
      with poor health outcomes. This study examines the longitudinal relationships
      between the number of hours of driving a bus in a city and blood pressure and
      musculoskeletal problems. METHODS: A prospective longitudinal design coupled with
      multilevel random coefficient modeling was used to examine the relationship among
      exposure to a job with high level of stress, urban bus driving, blood pressure,
      and musculoskeletal problems. Baseline blood pressure and musculoskeletal
      symptoms of men and women (n = 88) were assessed before they began driving a bus
      in central Stockholm. The number of hours of driving per week, blood pressure,
      and musculoskeletal symptoms were tracked for a period of 5 years. Multilevel
      random coefficient modeling techniques were used to model how individual
      trajectories of health effects were affected by the number of hours of driving,
      after statistically controlling for baseline preworking health measures. RESULTS:
      Controlling for sex and baseline health outcomes, the average number of hours of
      bus driving per week predicted higher diastolic blood pressure (B = 0.069,
      standard error = 0.034, p = .042) and more frequent musculoskeletal symptoms (B =
      0.013, standard error = 0.003, p < .001). CONCLUSIONS: The findings provide
      evidence for a positive association between the number of hours of bus driving
      and blood pressure and musculoskeletal problems. These findings are discussed in
      exposures to potentially toxic physical and psychosocial work-related factors.

PMID- 22155943
TI  - Genetic influences on life span and its relationship to personality: a 16-year
      follow-up study of a sample of aging twins.
AB  - OBJECTIVE: The relationship between personality and life span is not well
      understood, and no study to date has examined genetic influences underlying this
      relationship. The present study aimed to explore the phenotypic and genetic
      relationship between personality and life span, as well as genetic influences on
      all-cause mortality. METHODS: Prospective community-based study including 3752
      twin individuals older than 50 years. Neuroticism, psychoticism, extraversion,
      and social desirability and pessimism/optimism were measured at baseline using
      the Revised Eysenck Personality Questionnaire and the Revised Life Orientation
      Test, respectively. Information on age at death was obtained 16 years after the
      initial assessment of personality. RESULTS: Extraversion was inversely related to
      mortality with the risk of death decreasing 3% per unit increase of the
      extraversion score. Psychoticism and pessimism were positively related to
      mortality with a 36% and 39% increase in risk of death per unit increase in the
      respective personality score. Heritability of life span was 7%. Cross-twin cross
      trait hazard ratios (HRs) were only significant for optimism/pessimism in
      monozygotic (MZ) twins with no significant differences in HRs between MZ and
      dizygotic twins in all traits; however, there was a trend for slightly higher HRs
      in MZ compared with dizygotic twins in psychoticism and optimism/pessimism.
      CONCLUSIONS: Extraversion, psychoticism, and optimism/pessimism are significant
      predictors of longevity; extraversion is associated with a reduction, and
      pessimism and psychoticism are associated with an increase in mortality risk.
      Genetic influences on longevity in Australian twins are very low (7%). Our data
      also suggest a small, albeit nonsignificant, genetic influence on the
      relationship of pessimism and psychoticism with life span.

PMID- 22155944
TI  - Preoperative cerebral hypoperfusion in the left, not in the right, hemisphere is
      associated with cognitive decline after cardiac surgery.
AB  - OBJECTIVE: Postoperative cognitive decline (POCD) is a frequent complication
      after cardiac surgery. Although intraoperative events are risk factors for POCD,
      the role played by preoperative hypoperfusion in cognitive decline has not yet
      been investigated. It is also unknown whether the impact of preoperative
      hypoperfusion in the left or right middle cerebral arteries (MCAs) can
      differentially account for POCD. The main aims of this study were to investigate
      whether preoperative cerebral hypoperfusion was associated with early POCD and
      whether lateralized hypoperfusion would differentially affect POCD in patients
      after cardiac surgery. METHODS: Bilateral MCA continuous transcranial Doppler
      (TCD) sonography was preoperatively performed at rest in 31 right-handed patients
      who underwent cardiac surgery to detect cerebral blood flow (CBF) velocity. All
      patients completed a neuropsychological evaluation to assess attention, short
      term memory, working memory, and psychomotor function before surgery and at
      discharge. POCD was defined using the standard deviation method. Logistic
      regression was used to investigate the association between hypoperfusion and
      POCD, controlling for common preoperative risk factors. RESULTS: Fourteen
      patients (45%) exhibited POCD. Cerebral hypoperfusion in the left MCA selectively
      predicted the incidence of POCD (odds ratio = 0.90, p < .02), whereas CBF
      velocity in the right MCA was unrelated to POCD (odds ratio = 1.07, p = .39).
      CONCLUSIONS: Patients who underwent cardiac surgery with reduced CBF velocity in
      the left MCA preoperatively are at greater risk for POCD. Left cerebral
      hypoperfusion may also represent an independent predictor of POCD in these
      patients. TCD evaluation may have substantial clinical benefits for the detection
      of patients at high risk of POCD after cardiac surgery.

PMID- 22155945
TI  - Advanced three-dimensional tailored RF pulse design in volume selective parallel
      excitation.
AB  - Volume selective excitation has a variety of uses in clinical magnetic resonance
      imaging, but can suffer from insufficient excitation accuracy and impractically
      long pulse duration in ultra-high field applications. Based on recently-developed
      parallel transmission techniques, an optimized 3D tailored radio-frequency RF
      (TRF) pulse, designed with a novel 3D adaptive trajectory, is proposed to improve
      and accelerate volume selective excitation. The trajectory is designed to be
      regular-shaped and adaptively stretched according to the size of a 3D k-space
      "trajectory container." The container is designed to hold most of the RF energy
      deposition responsible for the desired pattern in the excitation k-space in the
      use of the blurring patterns caused by the multichannel sensitivity maps. The
      proposed method can also be used to reduce both global and peak RF energy
      required during excitation. The feasibility of this method is confirmed by
      simulations of ultra-high field cases.

PMID- 22155946
TI  - GWAtoolbox: an R package for fast quality control and handling of genome-wide
      association studies meta-analysis data.
AB  - SUMMARY: The GWAtoolbox is an R package that standardizes and accelerates the
      handling of data from genome-wide association studies (GWAS), particularly in the
      context of large-scale GWAS meta-analyses. A key feature of GWAtoolbox is its
      ability to perform quality control (QC) of any number of files in a matter of
      minutes. The implemented workflow has been structured to check three particular
      data quality aspects: (i) data formatting, (ii) quality of the GWAS results and
      (iii) data consistency across studies. Output consists of an extensive list of
      quality statistics and plots which allow inspection of individual files and
      between-study comparison to identify systematic bias. AVAILABILITY:
      http://www.eurac.edu/GWAtoolbox CONTACT: cfuchsb@umich.edu;
      daniel.taliun@eurac.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 22155947
TI  - M(3): an improved SNP calling algorithm for Illumina BeadArray data.
AB  - SUMMARY: Genotype calling from high-throughput platforms such as Illumina and
      Affymetrix is a critical step in data processing, so that accurate information on
      genetic variants can be obtained for phenotype-genotype association studies. A
      number of algorithms have been developed to infer genotypes from data generated
      through the Illumina BeadStation platform, including GenCall, GenoSNP, Illuminus
      and CRLMM. Most of these algorithms are built on population-based statistical
      models to genotype every SNP in turn, such as GenCall with the GenTrain
      clustering algorithm, and require a large reference population to perform well.
      These approaches may not work well for rare variants where only a small
      proportion of the individuals carry the variant. A fundamentally different
      approach, implemented in GenoSNP, adopts a single nucleotide polymorphism (SNP)
      based model to infer genotypes of all the SNPs in one individual, making it an
      appealing alternative to call rare variants. However, compared to the population
      based strategies, more SNPs in GenoSNP may fail the Hardy-Weinberg Equilibrium
      test. To take advantage of both strategies, we propose a two-stage SNP calling
      procedure, named the modified mixture model (M(3)), to improve call accuracy for
      both common and rare variants. The effectiveness of our approach is demonstrated
      through applications to genotype calling on a set of HapMap samples used for
      quality control purpose in a large case-control study of cocaine dependence. The
      increase in power with M(3) is greater for rare variants than for common variants
      depending on the model. AVAILABILITY: M(3) algorithm:
      http://bioinformatics.med.yale.edu/group. CONTACT: name@bio.com;
      hongyu.zhao@yale.edu SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 22155948
TI  - Workplace-based breast cancer screening intervention in china.
AB  - BACKGROUND: Breast cancer continues to be the primary cause of death among East
      and Southeast Asian women. Although China, the most populous country in the
      world, is experiencing unprecedented economic growth, its health care system has
      yet to benefit from the current economic prosperity. Indeed, studies have shown a
      consistent increase in breast cancer rates among Chinese women over the past two
      decades in the absence of breast cancer screening guidelines. METHODS: The
      primary objective of this study was to examine the impact of a workplace
      intervention on increasing breast cancer screening rates. The study was
      implemented at eight worksites in Nanjing, four of which were assigned to the
      intervention group (n = 232) and four to the control group (n = 221). The
      intervention group received breast cancer education and screening navigation. The
      control group was provided with general cancer education and received a delayed
      intervention after completion of the study. Study measures were completed at pre-
      and postprogram and at 6-month follow-up to assess uptake of mammography.
      RESULTS: Baseline mammography use was low among both intervention and control
      groups. However, exposure to the workplace intervention dramatically increased
      the uptake of mammography from 10.3% at baseline to 72.6% at 6-month follow-up in
      the intervention group (P < 0.001). CONCLUSIONS: Findings provide preliminary
      evidence that the implementation of a comprehensive workplace breast cancer
      screening intervention program in China can lead to increased uptake of
      mammography. These data may help facilitate the development of theory-based
      workplace cancer prevention programs and screening guidelines in China. IMPACT: A
      workplace-based multifaceted intervention could have a strong impact in breast
      cancer prevention and early detection among women in China.

PMID- 22155949
TI  - The Or gene enhances carotenoid accumulation and stability during post-harvest
      storage of potato tubers.
AB  - Provitamin A carotenoids in staple crops are not very stable during storage and
      their loss compromises nutritional quality. To elucidate the fundamental
      mechanisms underlying carotenoid accumulation and stability, we investigated
      transgenic potato tubers that expressed the cauliflower Orange (Or) gene. We
      found that the Or transgene not only promoted retention of beta-carotene level,
      but also continuously stimulated its accumulation during 5 months of cold
      storage. In contrast, no increased levels of carotenoids were observed in the
      tubers of vector-only controls or a yellow-flesh variety during the same period
      of storage. The increased carotenoid accumulation was found to be associated with
      the formation of lipoprotein-carotenoid sequestering structures, as well as with
      the enhanced abundance of phytoene synthase, a key enzyme in the carotenoid
      biosynthetic pathway. Furthermore, the provitamin A carotenoids stored were shown
      to be stable during simulated digestion and accessible for uptake by human
      intestinal absorptive cells. Proteomic analysis identified three major functional
      groups of proteins (i.e. heat shock proteins, glutathione-S-transferases, and
      carbohydrate metabolic proteins) that are potentially important in the Or
      regulated carotenoid accumulation. Our results show that regulation of carotenoid
      sequestration capacity is an important mechanism by which carotenoid stability is
      regulated. Our findings suggest that induction of a proper sink structure
      formation in staple crops may provide the crops with a unique ability to promote
      and/or stabilize provitamin A accumulation during plant growth and post-harvest
      storage.

PMID- 22155951
TI  - Characterization of surface stiffness and probe-sample dissipation using the band
      excitation method of atomic force microscopy: a numerical analysis.
AB  - Recently Jesse and co-workers introduced the band excitation atomic force
      microscopy (BE-AFM) method (Jesse et al 2007 Nanotechnology 18 435503), in which
      the cantilever probe is excited in a continuum frequency band in order to measure
      its response at all frequencies in the band. Analysis of the cantilever response
      using the damped harmonic oscillator model provides information on the stiffness
      and level of dissipation at the tip-sample junction as the sample is scanned.
      Since its introduction, this method has been used in magnetic, electromechanical,
      thermal and molecular unfolding applications, among others, and has given rise to
      a new family of scanning probe microscopy techniques. Additionally, the concept
      is applicable to any field in which measurement of the frequency response of
      harmonic oscillators is relevant. In this paper we present an analytical and
      numerical analysis of the excitation signals used in BE-AFM, as well as of the
      cantilever response under different conditions. Our analysis is performed within
      the context of viscoelastic characterization. We discuss subtleties in the
      cantilever dynamics, provide guidelines for implementing the method effectively
      and illustrate the use of simulation in interpreting the results.

PMID- 22155950
TI  - Auxin biosynthesis: a simple two-step pathway converts tryptophan to indole-3
      acetic acid in plants.
AB  - Indole-3-acetic acid (IAA), the main naturally occurring auxin, is essential for
      almost every aspect of plant growth and development. However, only recently have
      studies finally established the first complete auxin biosynthesis pathway that
      converts tryptophan (Trp) to IAA in plants. Trp is first converted to indole-3
      pyruvate (IPA) by the TAA family of amino transferases and subsequently IAA is
      produced from IPA by the YUC family of flavin monooxygenases. The two-step
      conversion of Trp to IAA is the main auxin biosynthesis pathway that plays an
      essential role in many developmental processes.

PMID- 22155952
TI  - PDE-based enhancement of color images in RGB space.
AB  - A novel method for color image enhancement is proposed as an extension of the
      scalar-diffusion-shock-filter coupling model, where noisy and blurred images are
      denoised and sharpened. The proposed model is based on using the single vectors
      of the gradient magnitude and the second derivatives as a manner to relate
      different color components of the image. This model can be viewed as a
      generalization of the Bettahar-Stambouli filter to multivalued images. The
      proposed algorithm is more efficient than the mentioned filter and some previous
      works at color images denoising and deblurring without creating false colors.

PMID- 22155953
TI  - Camera-pose estimation via projective Newton optimization on the manifold.
AB  - Determining the pose of a moving camera is an important task in computer vision.
      In this paper, we derive a projective Newton algorithm on the manifold to refine
      the pose estimate of a camera. The main idea is to benefit from the fact that the
      3-D rigid motion is described by the special Euclidean group, which is a
      Riemannian manifold. The latter is equipped with a tangent space defined by the
      corresponding Lie algebra. This enables us to compute the optimization direction,
      i.e., the gradient and the Hessian, at each iteration of the projective Newton
      scheme on the tangent space of the manifold. Then, the motion is updated by
      projecting back the variables on the manifold itself. We also derive another
      version of the algorithm that employs homeomorphic parameterization to the
      special Euclidean group. We test the algorithm on several simulated and real
      image data sets. Compared with the standard Newton minimization scheme, we are
      now able to obtain the full numerical formula of the Hessian with a 60% decrease
      in computational complexity. Compared with Levenberg-Marquardt, the results
      obtained are more accurate while having a rather similar complexity.

PMID- 22155954
TI  - Semisupervised biased maximum margin analysis for interactive image retrieval.
AB  - With many potential practical applications, content-based image retrieval (CBIR)
      has attracted substantial attention during the past few years. A variety of
      relevance feedback (RF) schemes have been developed as a powerful tool to bridge
      the semantic gap between low-level visual features and high-level semantic
      concepts, and thus to improve the performance of CBIR systems. Among various RF
      approaches, support-vector-machine (SVM)-based RF is one of the most popular
      techniques in CBIR. Despite the success, directly using SVM as an RF scheme has
      two main drawbacks. First, it treats the positive and negative feedbacks equally,
      which is not appropriate since the two groups of training feedbacks have distinct
      properties. Second, most of the SVM-based RF techniques do not take into account
      the unlabeled samples, although they are very helpful in constructing a good
      classifier. To explore solutions to overcome these two drawbacks, in this paper,
      we propose a biased maximum margin analysis (BMMA) and a semisupervised BMMA
      (SemiBMMA) for integrating the distinct properties of feedbacks and utilizing the
      information of unlabeled samples for SVM-based RF schemes. The BMMA
      differentiates positive feedbacks from negative ones based on local analysis,
      whereas the SemiBMMA can effectively integrate information of unlabeled samples
      by introducing a Laplacian regularizer to the BMMA. We formally formulate this
      problem into a general subspace learning task and then propose an automatic
      approach of determining the dimensionality of the embedded subspace for RF.
      Extensive experiments on a large real-world image database demonstrate that the
      proposed scheme combined with the SVM RF can significantly improve the
      performance of CBIR systems.

PMID- 22155955
TI  - Locally oriented optical flow computation.
AB  - This paper proposes the use of an adaptive locally oriented coordinate frame when
      calculating an optical flow field. The coordinate frame is aligned with the least
      curvature direction in a local window about each pixel. This has advantages to
      both fitting the flow field to the image data and in imposing smoothness
      constraints between neighboring pixels. In terms of fitting, robustness is
      obtained to a wider variety of image motions due to the extra invariance provided
      by the coordinate frame. Smoothness constraints are naturally propagated along
      image boundaries which often correspond to motion boundaries. In addition, moving
      objects can be efficiently segmented in the least curvature direction. We show
      experimentally the benefits of the method and demonstrate robustness to fast
      rotational motion, such as what often occurs in human motion.

PMID- 22155956
TI  - Design and optimization of color lookup tables on a simplex topology.
AB  - An important computational problem in color imaging is the design of color
      transforms that map color between devices or from a device-dependent space (e.g.,
      RGB/CMYK) to a device-independent space (e.g., CIELAB) and vice versa. Real-time
      processing constraints entail that such nonlinear color transforms be implemented
      using multidimensional lookup tables (LUTs). Furthermore, relatively sparse LUTs
      (with efficient interpolation) are employed in practice because of storage and
      memory constraints. This paper presents a principled design methodology rooted in
      constrained convex optimization to design color LUTs on a simplex topology. The
      use of   n simplexes, i.e., simplexes in  n dimensions, as opposed to traditional
      lattices, recently has been of great interest in color LUT design for simplex
      topologies that allow both more analytically tractable formulations and greater
      efficiency in the LUT. In this framework of  n-simplex interpolation, our central
      contribution is to develop an elegant iterative algorithm that jointly optimizes
      the placement of nodes of the color LUT and the output values at those nodes to
      minimize interpolation error in an expected sense. This is in contrast to
      existing work, which exclusively designs either node locations or the output
      values. We also develop new analytical results for the problem of node location
      optimization, which reduces to constrained optimization of a large but sparse
      interpolation matrix in our framework. We evaluate our  n -simplex color LUTs
      against the state-of-the-art lattice (e.g., International Color Consortium
      profiles) and simplex-based techniques for approximating two representative
      multidimensional color transforms that characterize a CMYK xerographic printer
      and an RGB scanner, respectively. The results show that color LUTs designed on
      simplexes offer very significant benefits over traditional lattice-based
      alternatives in improving color transform accuracy even with a much smaller
      number of nodes.

PMID- 22155957
TI  - Content-adaptive motion estimation algorithm for coarse-grain SVC.
AB  - A joint model of scalable video coding (SVC) uses exhaustive mode and motion
      searches to select the best prediction mode and motion vector for each macroblock
      (MB) with high coding efficiency at the cost of computational complexity. If
      major characteristics of a coding MB such as the complexity of the prediction
      mode and the motion property can be identified and used in adjusting motion
      estimation (ME), one can design an algorithm that can adapt coding parameters to
      the video content. This way, unnecessary mode and motion searches can be avoided.
      In this paper, we propose a content-adaptive ME for SVC, including analyses of
      mode complexity and motion property to assist mode and motion searches. An
      experimental analysis is performed to study interlayer and spatial correlations
      in the coding information. Based on the correlations, the motion and mode
      characteristics of the current MB are identified and utilized to adjust each step
      of ME at the enhancement layer including mode decision, search-range selection,
      and prediction direction selection. Experimental results show that the proposed
      algorithm can significantly reduce the computational complexity of SVC while
      maintaining nearly the same rate distortion performance as the original encoder.

PMID- 22155958
TI  - On the construction of topology-preserving deformation fields.
AB  - In this paper, we investigate a new method to enforce topology preservation on
      deformation fields. The method is composed of two steps. The first one consists
      in correcting the gradient vector fields of the deformation at the discrete
      level, in order to fulfill a set of conditions ensuring topology preservation in
      the continuous domain after bilinear interpolation. This part, although related
      to prior works by Karacali and Davatzikos, proposes a new approach based on
      interval analysis. The second one aims to reconstruct the deformation, given its
      full set of discrete gradient vectors. The problem is phrased as a functional
      minimization problem on the convex subset  K of the Hilbert space  V. The
      existence and uniqueness of the solution of the problem are established, and the
      use of Lagrange's multipliers allows to obtain the variational formulation of the
      problem on the Hilbert space  V . Experimental results demonstrate the efficiency
      of the method.

PMID- 22155959
TI  - Methodology for reconstructing early zebrafish development from in vivo
      multiphoton microscopy.
AB  - Investigating cell dynamics during early zebrafish embryogenesis requires
      specific image acquisition and analysis strategies. Multiharmonic microscopy,
      i.e., second- and third-harmonic generations, allows imaging cell divisions and
      cell membranes in unstained zebrafish embryos from 1- to 1000-cell stage. This
      paper presents the design and implementation of a dedicated image processing
      pipeline (tracking and segmentation) for the reconstruction of cell dynamics
      during these developmental stages. This methodology allows the reconstruction of
      the cell lineage tree including division timings, spatial coordinates, and cell
      shape until the 1000-cell stage with minute temporal accuracy and micrometer
      spatial resolution. Data analysis of the digital embryos provides an extensive
      quantitative description of early zebrafish embryogenesis.

PMID- 22155960
TI  - Adaptive compressed sensing recovery utilizing the property of signal's
      autocorrelations.
AB  - Perfect compressed sensing (CS) recovery can be achieved when a certain basis
      space is found to sparsely represent the original signal. However, due to the
      diversity of the signals, there does not exist a universal predetermined basis
      space that can sparsely represent all kinds of signals, which results in an
      unsatisfying performance. To improve the accuracy of recovered signal, this paper
      proposes an adaptive basis CS reconstruction algorithm by minimizing the rank of
      an accumulated matrix (MRAM), whose eigenvectors approximate the optimal basis
      sparsely representing the original signal. The accumulated matrix is constructed
      to efficiently exploit the second-order statistical property of the signal's
      autocorrelations. Based on the theory of matrix completion, MRAM reconstructs the
      original signal from its random projections under the observation that the
      constructed accumulated matrix is of low rank for most natural signals such as
      periodic signals and those coming from an autoregressive stationary process.
      Experimental results show that the proposed MRAM efficiently improves the
      reconstruction quality compared with the existing algorithms.

PMID- 22155961
TI  - Interlayer bit allocation for scalable video coding.
AB  - In this paper, we present a theoretical analysis of the distortion in multilayer
      coding structures. Specifically, we analyze the prediction structure used to
      achieve temporal, spatial, and quality scalability of scalable video coding (SVC)
      and show that the average peak signal-to-noise ratio (PSNR) of SVC is a weighted
      combination of the bit rates assigned to all the streams. Our analysis utilizes
      the end user's preference for certain resolutions. We also propose a rate
      distortion (R-D) optimization algorithm and compare its performance with that of
      a state-of-the-art scalable bit allocation algorithm. The reported experiment
      results demonstrate that the R-D algorithm significantly outperforms the compared
      approach in terms of the average PSNR.

PMID- 22155962
TI  - Alleviating dirty-window effect in medium frame-rate binary video halftones.
AB  - A video display device having a lower number of bits per pixel than that required
      by the video to be displayed quantizes the video prior to its display. Halftoning
      can perform this quantization while attempting to reduce the visibility of
      certain quantization artifacts. Quantization artifacts are, nevertheless, not
      eliminated. A temporal artifact known as dirty-window effect (DWE) can be
      commonly observed in medium frame-rate binary video halftones. In this paper, we
      propose video halftone enhancement algorithms to reduce DWE. We assess the
      performance of the proposed algorithms by presenting objective measures for DWE
      in the original and the improved halftone videos. The expected contributions of
      this paper include three medium frame-rate binary video halftone enhancement
      algorithms that do the following: 1) reduce DWE under a spatial quality
      constraint; 2) reduce DWE under a spatial quality constraint with reduced
      complexity; and 3) reduce DWE under spatial and temporal quality constraints.

PMID- 22155963
TI  - Single frequency inverse obstacle scattering: a sparsity constrained linear
      sampling method approach.
AB  - The linear sampling method (LSM) offers a qualitative image reconstruction
      approach, which is known as a viable alternative for obstacle support
      identification to the well-studied filtered backprojection (FBP), which depends
      on a linearized forward scattering model. Of practical interest is the imaging of
      obstacles from sparse aperture far-field data under a fixed single frequency mode
      of operation. Under this scenario, the Tikhonov regularization typically applied
      to LSM produces poor images that fail to capture the obstacle boundary. In this
      paper, we employ an alternative regularization strategy based on constraining the
      sparsity of the solution's spatial gradient. Two regularization approaches based
      on the spatial gradient are developed. A numerical comparison to the FBP
      demonstrates that the new method's ability to account for aspect-dependent
      scattering permits more accurate reconstruction of concave obstacles, whereas a
      comparison to Tikhonov-regularized LSM demonstrates that the proposed approach
      significantly improves obstacle recovery with sparse-aperture data.

PMID- 22155964
TI  - TSK fuzzy function approximators: design and accuracy analysis.
AB  - Fuzzy systems are excellent approximators of known functions or for the dynamic
      response of a physical system. We propose a new approach to approximate any known
      function by a Takagi-Sugeno-Kang fuzzy system with a guaranteed upper bound on
      the approximation error. The new approach is also used to approximately represent
      the behavior of a dynamic system from its input-output pairs using experimental
      data with known error bounds. We provide sufficient conditions for this class of
      fuzzy systems to be universal approximators with specified error bounds. The new
      conditions require a smaller number of membership functions than all previously
      published conditions. We illustrate the new results and compare them to published
      error bounds through numerical examples.

PMID- 22155965
TI  - Noise-assisted correlation algorithm for suppressing noise-induced artifacts in
      ultrasonic Nakagami images.
AB  - Ultrasonic Nakagami images can complement conventional B-mode images for
      scatterer characterization. White noise in anechoic areas leads to artifacts that
      affect the Nakagami image to characterize tissues. Artifact removal requires
      rejection of the white noise without deforming the backscattered waveform. This
      study proposes a noise-assisted correlation algorithm (NCA) and carries out
      simulations, phantom experiments, and clinical measurements to validate its
      feasibility and practicality. The simulation results show that the NCA can reject
      white noise in an anechoic area without any deformation of the backscattered
      waveforms. The results obtained from phantoms and tissues further demonstrate
      that the proposed NCA can suppress a Nakagami image artifact without changing the
      texture of the Nakagami image of the scattering background. The NCA is an
      essential algorithm to construct artifact-free Nakagami image for correctly
      reflecting scatterer properties of biological tissues.

PMID- 22155966
TI  - Numerical simulations of odorant detection by biologically inspired sensor
      arrays.
AB  - The antennules of many marine crustaceans enable them to rapidly locate sources
      of odorant in turbulent environmental flows and may provide biological
      inspiration for engineered plume sampling systems. A substantial gap in knowledge
      concerns how the physical interaction between a sensing device and the chemical
      filaments forming a turbulent plume affects odorant detection and filters the
      information content of the plume. We modeled biological arrays of chemosensory
      hairs as infinite arrays of odorant flux-detecting cylinders and simulated the
      fluid flow around and odorant flux into the hair-like sensors as they intercepted
      a single odorant filament. As array geometry and sampling kinematics were varied,
      we quantified distortion of the flux time series relative to the spatial shape of
      the original odorant filament as well as flux metrics that may be important to
      both organisms and engineered systems attempting to measure plume structure
      and/or identify chemical composition. The most important predictor of signal
      distortion is the ratio of sensor diameter to odorant filament width. Achieving
      high peak properties (e.g. sharpness) of the flux time series and maximizing the
      total number of odorant molecules detected appear to be mutually exclusive design
      goals. Sensor arrays inspired specifically by the spiny lobster Panulirus argus
      and mantis shrimp Gonodactylaceus falcatus introduce little signal distortion but
      these species' neural systems may not be able to resolve plume structure at the
      level of individual filaments via temporal properties of the odorant flux.
      Current chemical sensors are similarly constrained. Our results suggest either
      that the spatial distribution of flux across the aesthetasc array is utilized by
      P. argus and G. falcatus, or that such high spatiotemporal resolution is
      unnecessary for effective plume tracking.

PMID- 22155967
TI  - Quantum oscillations and ferromagnetic hysteresis observed in iron filled
      multiwall carbon nanotubes.
AB  - We report on the electrical transport properties of single multiwall carbon
      nanotubes with and without an iron filling as a function of temperature and
      magnetic field. For the iron filled nanotubes the magnetoresistance shows a
      magnetic behavior induced by iron, which can be explained by taking into account
      a contribution of s-d hybridization. In particular, ferromagnetic-like hysteresis
      loops were observed up to 50 K for the iron filled multiwall carbon nanotubes.
      The magnetoresistance shows quantum interference phenomena such as universal
      conductance fluctuations and weak localization effects.

PMID- 22155968
TI  - Off-center displacements and hydrostatic pressure induced phase transition in
      perovskites.
AB  - Pressure has a profound effect on the paraelectric and ferroelectric properties
      of perovskite crystals. In this paper we theoretically investigate the effect of
      pressure on the cubic-to-tetragonal phase transition and on the soft mode
      dynamics of some classical perovskite crystals: BaTiO(3), PbTiO(3), and KNbO(3).
      We use a model consisting of three subsystems: electrons, phonons, and off-center
      displacements treated as spins. Experiments show that pressure has a large effect
      on the tunneling and hopping of the off-center displacements, that in turn
      strongly affect the pressure dependence of the transition temperature and the
      soft mode frequency. This model, with a very small number of adjustable
      parameters, accounts quantitatively for the experimentally measured nonlinear
      pressure dependence of the cubic-to-tetragonal phase transition temperature, up
      to the critical pressure where the transition temperature is zero. It also
      accounts quantitatively for the pressure dependence of the soft mode frequency,
      which is finite at the phase transition in spite of the fact that the phase
      transition at elevated pressures is second order, and for the pressure dependence
      of the electronic gap energy.

PMID- 22155969
TI  - Muscle stiffness at different force levels measured with two myotonometric
      devices.
AB  - Myotonometric measurements are quantitative methods of muscle tone assessment and
      may be used as an alternative for palpation evaluation. The objective of the
      study was to compare the measurements of brachioradialis muscle tone and
      stiffness using the Myoton-3 and the Myotonometer. The participants were young
      males (N = 17, mean age 21 +/- 1 years). The skeletal muscle state was expressed
      by the Myoton-3 parameters stiffness (N m(-1)), frequency (Hz) and decrement (no
      unit) and the Myotonometer's area under the curve (AUC) parameter (area under the
      curve, no unit), when muscle was at rest and during activity at 25%, 50%, 80% and
      100% of maximal voluntary contraction for elbow flexors. Pearson's correlation
      between AUC and stiffness is r = -0.89, AUC and frequency r = -0.84 and AUC and
      decrement r = 0.79, p < 0.01. When comparing the results from each experimental
      condition separately for frequency and AUC, the correlation was from -0.63 to 
      0.80, for stiffness and AUC it ranged from -0.25 to -0.75 and for decrement and
      AUC from 0.27 to 0.74. The degree of correlation between myotonometric
      measurements depends on whether the measured muscle is at rest or during
      contraction. The correlation is diverse among related parameters.

PMID- 22155970
TI  - Patterning of periodic nano-cavities on PEDOT-PSS using nanosphere-assisted near
      field optical enhancement and laser interference lithography.
AB  - A simple approach for creating periodic nano-cavities and periodic stripes of
      nano-cavity arrays on poly (3,4-ethylene dioxythiophene)-poly(styrenesulfonate)
      (PEDOT-PSS) thin films using a combination of optical near-field enhancement
      through self-assembled silica nanospheres and laser interference lithography is
      presented. Monolayers of close-packed silica nanospheres (800, 600, and 430 nm in
      diameter) are self-assembled on 2 um thick PEDOT-PSS electropolymerized films and
      are subsequently irradiated with 10 ns pulses of 355 nm wavelength laser light.
      Over areas spanning 2 cm(2), circular nano-cavities with central holes of size 50
      200 nm and surrounding craters of size 100-400 nm are formed in the PEDOT-PSS
      films directly underneath the nanospheres due to strong enhancement (11-18 fold)
      of the incident light in the near-field, which is confirmed through Mie
      scattering theory. Predictions from theoretical simulations examining the
      combined effects of near-field enhancement and interference are in good agreement
      with the experimental results. The results illustrate the versatility of the
      described technique for creating nano-cavity arrays or nano-pores in PEDOT-PSS
      over large areas with designed periodicity and hole size.

PMID- 22155971
TI  - Improved single- and multi-contact life-time testing of dental restorative
      materials using key characteristics of the human masticatory system and a
      force/position-controlled robotic dental wear simulator.
AB  - This paper presents a new in vitro wear simulator based on spatial parallel
      kinematics and a biologically inspired implicit force/position hybrid controller
      to replicate chewing movements and dental wear formations on dental components,
      such as crowns, bridges or a full set of teeth. The human mandible, guided by
      passive structures such as posterior teeth and the two temporomandibular joints,
      moves with up to 6 degrees of freedom (DOF) in Cartesian space. The currently
      available wear simulators lack the ability to perform these chewing movements. In
      many cases, their lack of sufficient DOF enables them only to replicate the
      sliding motion of a single occlusal contact point by neglecting rotational
      movements and the motion along one Cartesian axis. The motion and forces of more
      than one occlusal contact points cannot accurately be replicated by these
      instruments. Furthermore, the majority of wear simulators are unable to control
      simultaneously the main wear-affecting parameters, considering abrasive
      mechanical wear, which are the occlusal sliding motion and bite forces in the
      constraint contact phase of the human chewing cycle. It has been shown that such
      discrepancies between the true in vivo and the simulated in vitro condition
      influence the outcome and the quality of wear studies. This can be improved by
      implementing biological features of the human masticatory system such as tooth
      compliance realized through the passive action of the periodontal ligament and
      active bite force control realized though the central nervous system using
      feedback from periodontal preceptors. The simulator described in this paper can
      be used for single- and multi-occlusal contact testing due to its kinematics and
      ability to exactly replicate human translational and rotational mandibular
      movements with up to 6 DOF without neglecting movements along or around the three
      Cartesian axes. Recorded human mandibular motion and occlusal force data are the
      reference inputs of the simulator. Experimental studies of wear using this
      simulator demonstrate that integrating the biological feature of combined
      force/position hybrid control in dental material testing improves the linearity
      and reduces the variability of results. In addition, it has been shown that
      present biaxially operated dental wear simulators are likely to provide
      misleading results in comparative in vitro/in vivo one-contact studies due to
      neglecting the occlusal sliding motion in one plane which could introduce an
      error of up to 49% since occlusal sliding motion D and volumetric wear loss
      V(loss) are proportional.

PMID- 22155972
TI  - Evaluating the genotoxicity of topoisomerase-targeted antibiotics.
AB  - Antibiotics like fluoroquinolones (FQs) that target bacterial type II
      topoisomerases pose a potential genotoxic risk due to interactions with mammalian
      topoisomerase II (TOPO II) counterparts. Inhibition of TOPO II can lead to the
      generation of clastogenic DNA double-strand breaks (DSBs) that can in turn
      manifest in mutagenesis. Thus, methods that allow early identification of drugs
      that present the greatest hazard are warranted. A rapid, medium-throughput and
      predictive genotoxicity screen that can be applied to bacterial type II
      topoisomerase inhibitors is described herein. Maximal induction of the DSB
      biomarker serine139-phosphorylated histone H2AX (gammaH2AX) in L5178Y cells was
      quantified via flow cytometry and correlated with data derived from the mouse
      lymphoma screen (MLS), a default assay used to rank genotoxic potential. When
      applied to a class of novel bacterial type II topoisomerase inhibitors (NBTIs) in
      lead-optimisation, maximal gammaH2AX induction >1.4-fold (relative to controls)
      identified 22/27 NBTIs that induced >6-fold relative mutation frequency (MF) in
      MLS. Moreover, response signatures comprising of gammaH2AX induction and G(2)M
      cell cycle arrest elucidated using this approach suggested that these NBTIs,
      primarily of the H class, operated via a TOPO II poison-like mechanism of action
      (MoA) similar to FQs. NBTIs that induced <=6-fold relative MF, which were mainly
      A class-derived, had less impact on gammaH2AX (<=1.4-fold) and also evoked G(1)
      arrest, indicating that their cytotoxic effects were likely mediated through a
      non-poison MoA. Concordance between assays was 86% (54/63) when 1.4- and 6-fold
      'cut offs' were applied. These findings were corroborated through inspection of
      human TOPO IIalpha IC(50) data as NBTIs exhibiting equivalent inhibitory
      capacities had differing genotoxic potencies. Deployed in an early screening
      capacity, the gammaH2AX by flow assay coupled with structure-activity
      relationship evaluation can provide insight into MoA and impact medicinal
      chemistry efforts, ultimately leading to the production of inherently safer
      molecules.

PMID- 22155973
TI  - Computer-based safety surveillance and patient-centered health records.

PMID- 22155977
TI  - Nickel-assisted growth and selective doping of spinel-like gallium oxide
      nanocrystals in germano-silicate glasses for infrared broadband light emission.
AB  - The target of taking advantage of the near-infrared light-emission properties of
      nickel ions in crystals for the design of novel broadband optical amplifiers
      requires the identification of suitable nanostructured glasses able to embed Ni
      doped nanocrystals and to preserve the workability of a glass. Here we show that
      Ni doping of Li(2)O-Na(2)O-Ga(2)O(3)-GeO(2)-SiO(2) glass (with composition
      7.5:2.5:20:35:35 and melting temperature 1480  degrees C, sensibly lower than in
      Ge-free silicates) enables the selective embedding of nickel ions in thermally
      grown nanocrystals of spinel-like gallium oxide. The analysis of transmission
      electron microscopy and x-ray diffraction data as a function of Ni-content (from
      0.01 to 1 mol%) indicates that Ni ions promote the nanophase crystallization
      without affecting nanoparticle size (~6 nm) and concentration (~4 * 10(18) cm(
      3)). Importantly, as shown by optical absorption spectra, all nickel ions enter
      into the nanophase, with a number of ions per nanocrystal that depends on the
      nanocrystal concentration and ranges from 1 to 10(2). Photoluminescence data
      indicate that fast non-radiative decay processes become relevant only at mean ion
      ion distances shorter than 1.4 nm, which enables the incorporation of a few Ni
      ions per nanoparticle without too large a worsening of the light-emission
      efficiency. Indeed, at 0.1 mol% nickel, the room temperature quantum yield is 9%,
      with an effective bandwidth of 320 nm.

PMID- 22155978
TI  - Homogeneous switching in ultrathin ferroelectric films.
AB  - It is well known that there are two possible switching mechanisms in
      ferroelectric crystals and films (see, e.g., Tagantsev et al 2010 Domains in
      Ferroic Crystals and Thin Films (Berlin: Springer)). The first mechanism, which
      follows from the mean-field theory of Landau-Ginzburg, is a homogeneous one and
      does not connect domains. This mechanism was never observed before 1998. The
      second mechanism, connected with nucleation and domain movement, is common for
      the ferroelectrics and is well known from the time of domain discovery (1956). In
      the present paper the existence of a homogeneous mechanism of switching in
      ultrathin copolymer films is confirmed by piezoresponse force microscopy. The
      results of the present paper permit us to suppose that homogeneous switching
      exists in other ultrathin ferroelectric films.

PMID- 22155974
TI  - A systematic review to evaluate the accuracy of electronic adverse drug event
      detection.
AB  - OBJECTIVE: Adverse drug events (ADEs), defined as adverse patient outcomes caused
      by medications, are common and difficult to detect. Electronic detection of ADEs
      is a promising method to identify ADEs. We performed this systematic review to
      characterize established electronic detection systems and their accuracy.
      METHODS: We identified studies evaluating electronic ADE detection from the
      MEDLINE and EMBASE databases. We included studies if they contained original data
      and involved detection of electronic triggers using information systems. We
      abstracted data regarding rule characteristics including type, accuracy, and
      rationale. RESULTS: Forty-eight studies met our inclusion criteria. Twenty-four
      (50%) studies reported rule accuracy but only 9 (18.8%) utilized a proper gold
      standard (chart review in all patients). Rule accuracy was variable and often
      poor (range of sensitivity: 40%-94%; specificity: 1.4%-89.8%; positive predictive
      value: 0.9%-64%). 5 (10.4%) studies derived or used detection rules that were
      defined by clinical need or the underlying ADE prevalence. Detection rules in 8
      (16.7%) studies detected specific types of ADEs. CONCLUSION: Several factors led
      to inaccurate ADE detection algorithms, including immature underlying information
      systems, non-standard event definitions, and variable methods for detection rule
      validation. Few ADE detection algorithms considered clinical priorities. To
      enhance the utility of electronic detection systems, there is a need to
      systematically address these factors.

PMID- 22155979
TI  - Is tendon stiffness correlated to the dissipation coefficient?
AB  - The assessment of Achilles tendon mechanical properties in vivo has received much
      attention in the literature. Many studies investigated mechanical properties by
      assessing tendon stiffness. Despite tendon dissipative properties being
      representative of a storage-recoil process, its determination has received
      minimal attention in the literature. The aim of this study was to determine if
      Achilles tendon stiffness is associated with dissipative properties. The cross
      sectional area, stiffness and dissipation coefficient of the Achilles tendon were
      measured in 35 subjects. No significant correlation was found between stiffness
      and the dissipation coefficient, irrespective of stiffness normalization with
      cross-sectional area (P > 0.05). Thus, it appears that both stiffness and
      dissipative properties must be assessed to determine the storage-recoil process
      capacities of the Achilles tendon in order to precisely characterize changes in
      the tendon mechanical properties after chronic interventions or rehabilitation
      programs.

PMID- 22155980
TI  - Single digit nanofabrication by step-and-repeat nanoimprint lithography.
AB  - A novel strategy for fabricating nanoimprint templates with sub-10 nm patterns is
      demonstrated by combining electron beam lithography and atomic layer deposition.
      Nanostructures are replicated by step-and-repeat nanoimprint lithography and
      successfully transferred into functional material with high fidelity. The process
      extends the capacity of step-and-repeat nanoimprint lithography as a single digit
      nanofabrication method. Using the ALD process for feature shrinkage, we identify
      a size dependent deposition rate.

PMID- 22155981
TI  - Studying nanostructured nipple arrays of moth eye facets helps to design better
      thin film solar cells.
AB  - Nipples on the surface of moth eye facets exhibit almost perfect broadband anti
      reflection properties. We have studied the facet surface micro-protuberances,
      known as corneal nipples, of the chestnut leafminer moth Cameraria ohridella by
      atomic force microscopy, and simulated the optics of the nipple arrays by three
      dimensional electromagnetic simulation. The influence of the dimensions and
      shapes of the nipples on the optics was studied. In particular, the shape of the
      nipples has a major influence on the anti-reflection properties. Furthermore, we
      transferred the structure of the almost perfect broadband anti-reflection
      coatings to amorphous silicon thin film solar cells. The coating that imitates
      the moth-eye array allows for an increase of the short circuit current and
      conversion efficiency of more than 40%.

PMID- 22155982
TI  - Cortical activation changes underlying stimulation-induced behavioural gains in
      chronic stroke.
AB  - Transcranial direct current stimulation, a form of non-invasive brain
      stimulation, is showing increasing promise as an adjunct therapy in
      rehabilitation following stroke. However, although significant behavioural
      improvements have been reported in proof-of-principle studies, the underlying
      mechanisms are poorly understood. The rationale for transcranial direct current
      stimulation as therapy for stroke is that therapeutic stimulation paradigms
      increase activity in ipsilesional motor cortical areas, but this has not
      previously been directly tested for conventional electrode placements. This study
      was performed to test directly whether increases in ipsilesional cortical
      activation with transcranial direct current stimulation are associated with
      behavioural improvements in chronic stroke patients. Patients at least 6 months
      post-first stroke participated in a behavioural experiment (n = 13) or a
      functional magnetic resonance imaging experiment (n = 11), each investigating the
      effects of three stimulation conditions in separate sessions: anodal stimulation
      to the ipsilesional hemisphere; cathodal stimulation to the contralesional
      hemisphere; and sham stimulation. Anodal (facilitatory) stimulation to the
      ipsilesional hemisphere led to significant improvements (5-10%) in response times
      with the affected hand in both experiments. This improvement was associated with
      an increase in movement-related cortical activity in the stimulated primary motor
      cortex and functionally interconnected regions. Cathodal (inhibitory) stimulation
      to the contralesional hemisphere led to a functional improvement only when
      compared with sham stimulation. We show for the first time that the significant
      behavioural improvements produced by anodal stimulation to the ipsilesional
      hemisphere are associated with a functionally relevant increase in activity
      within the ipsilesional primary motor cortex in patients with a wide range of
      disabilities following stroke.

PMID- 22155984
TI  - In vitro sensitivities to UVA of lymphocytes from patients with colon and
      melanoma cancers and precancerous states in the micronucleus and the Comet
      assays.
AB  - To use lymphocytes as surrogate cells to investigate their in vitro sensitivities
      to ultraviolet (UV) treatment in different cancers and precancerous states by
      comparison with lymphocytes from healthy control individuals was the main aim of
      this research. UV light induces precise cellular and genomic mutations. In this
      study, the effect of ultraviolet A (UVA) (320-400 nm) was used as a generic
      mutagen to evaluate in vitro different sensitivities from lymphocytes of patients
      with suspected melanoma (SM), malignant melanoma (MM), polyposis coli (PC) and
      colorectal cancer (CRC). DNA damage was evaluated by two different methods: the
      micronucleus (MN) assay and the Comet assay. The baseline frequency of MNs was
      significantly increased in lymphocytes from all patients (SM, MM, PC and CRC)
      when compared to healthy individuals. After UV irradiation, MN frequencies were
      significantly increased in lymphocytes of all groups, both patients and healthy
      individuals. However, the MN frequency in all patient groups was significantly
      higher than in the healthy individual group. Similar results for the induction of
      genomic DNA damage were obtained for the Comet assay. Also for the Comet assay,
      UVA-induced DNA damage for all four patient groups was significantly increased
      when compared to healthy individuals (SM, MM, PC and CRC groups: P < 0.001).
      Conclusively, peripheral lymphocytes from patients with cancers MM and CRC or
      precancerous states SM and PC are more sensitive to a generic mutagen such as UVA
      than lymphocytes from healthy individuals. This feature may be used as an
      essential biomarker to screen and diagnose precancerous states and cancers in
      early stages.

PMID- 22155983
TI  - Behaviour, physiology and experience of pathological laughing and crying in
      amyotrophic lateral sclerosis.
AB  - Pathological laughing and crying is a disorder of emotional expression seen in a
      number of neurological diseases. The aetiology is poorly understood, but clinical
      descriptions suggest a disorder of emotion regulation. The goals of this study
      were: (i) to characterize the subjective, behavioural and physiological emotional
      reactions that occur during episodes of pathological laughing and crying; (ii) to
      compare responses during these episodes to those that occur when emotions are
      elicited under standard conditions (watching sad and amusing emotional films,
      being startled); and (iii) to examine the ability of patients with this disorder
      to regulate their emotions under standardized conditions. Twenty-one patients
      with pathological laughing and crying due to amyotrophic lateral sclerosis and 14
      with amyotrophic lateral sclerosis but no pathological laughing and crying were
      studied. Emotional measures included self-reported emotional experience, video
      recordings of facial reactivity and peripheral physiological responses (skin
      conductance, heart rate and somatic activity). Nineteen of the 21 patients with
      histories of pathological laughing and crying had at least one episode in the
      laboratory that they agreed constituted pathological laughing or crying (a total
      of 56 episodes were documented). Compared with viewing sad and amusing films, the
      episodes were associated with greater facial and physiological activation.
      Contrary to many clinical descriptions, episodes were often induced by
      contextually appropriate stimuli and associated with strong experiences of
      emotion that were consistent with the display. When instructed to regulate their
      facial responses to emotion-eliciting films, patients with pathological laughing
      and crying showed impairments compared with patients who did not have a history
      of this disorder. These findings support the idea that pathological laughing and
      crying represents activation of all channels of emotional responding (i.e.
      behavioural, physiological and subjective). Furthermore, they support previously
      advanced theories that, rather than being associated with general emotional
      hyperreactivity, this disorder may be due to dysfunction in frontal neural
      systems that support voluntary regulation of emotion.

PMID- 22155985
TI  - Evolution of the commensurate and incommensurate magnetic phases of the S = 3/2
      kagome staircase Co3V2O8 in an applied field.
AB  - Single crystal neutron diffraction studies have been performed on the S = 3/2
      kagome staircase compound Co(3)V(2)O(8) with a magnetic field applied along the
      magnetization easy-axis ([Formula: see text]). Previous zero-field measurements
      (Chen Y et al 2006 Phys. Rev. B 74 014430) reported a rich variety of magnetic
      phases, with a ferromagnetic ground state as well as incommensurate, transversely
      polarized spin density wave (SDW) phases (with a propagation vector of [Formula:
      see text]) interspersed with multiple commensurate lock-in transitions. The
      magnetic phase diagram with [Formula: see text] adds further complexity. For
      small applied fields, MU(0)H ~ 0.05 T, the commensurate lock-in phases are
      destabilized in favor of the incommensurate SDW ones, while slightly larger
      applied fields restore the commensurate lock-in phase with delta = 1/2 and yield
      a new commensurate phase with delta = 2/5. For measurements in an applied field,
      higher-order scattering is observed that corresponds to the second harmonic.

PMID- 22155986
TI  - Recent advances in the monitoring and control of haemodynamic variables during
      haemodialysis: a review.
AB  - The human body possesses a unique set of organs that are responsible for
      providing homeostatic balance to the body's fluids. Of these, the kidneys
      regulate fluid and electrolyte balance in order to maintain the intracellular and
      extracellular fluid volumes and ion composition within tight limits. When kidneys
      fail to function normally, fluid is retained and several ions and solutes
      accumulate. The consequences may be life threatening. Many kidney failure
      patients rely on haemodialysis (HD) as a life sustaining therapy to remove the
      waste products and excess fluid from the circulating blood. HD is based on the
      principle of diffusion of solutes and ultrafiltration of fluid across a semi
      permeable membrane. Fluid removal during HD results in relative hypovolaemia
      during which the stability of a patient relies on compensatory mechanisms to
      maintain blood pressure (BP). The major compensatory mechanisms include
      sympathetic nervous system activation of peripheral vasoconstriction together
      with modest heart rate acceleration to ensure the haemodynamic stability of the
      patient. Over the years, many monitoring tools have been developed in the hope of
      predicting intra-dialytic hypotensive episodes. Similarly many methods have been
      utilized to prevent dialysis-induced complications: ultrafiltration and dialysate
      sodium profiling, varying ultrafiltration based on frequent BP measurements, etc.
      This paper provides a comprehensive review of those monitoring and control tools.
      It starts with a brief introduction to human kidneys and dialysis for non
      specialized readers. The paper then reviews the monitoring tools that have been
      applied to assess the physiological response of patients during HD. This is
      followed by control techniques used to prevent dialysis-induced complications.

PMID- 22155987
TI  - Site-selective synthesis of silver nanoparticles in pre-patterned trenches and
      their localized surface plasmon resonances.
AB  - A method for depositing silver nanoparticles in a pre-patterned trench by site
      selective synthesis is described. In the trench patterns with various shapes,
      silver nanoparticles can be selectively nucleated and grown only on
      polyvinylpyrrolidone (PVP) domains by attraction (or repulsion) between silver
      ions and the hydrophilic PVP island domains in a silica matrix of the trench (or
      the hydrophobic fluorosilane layer). Regarding the silver nanoparticles in the
      trench, localized surface plasmon resonance (LSPR) could be excited by obliquely
      incident light, reradiating the enhanced electromagnetic field in the far- and
      near-fields. Even in the case of a large angle incidence in total internal
      reflection (TIR), the patterned silver nanoparticle clusters underwent strong
      scattering with a high intensity, due to the LSPR effect.

PMID- 22155988
TI  - An oscillator network exhibiting a long-lasting response to an external signal.
AB  - This study proposes an oscillator network to model the long-lasting responses
      observed in neural circuits. The responses of the proposed network model are
      represented by the temporal synchronization of the oscillators. The response
      duration does not depend on the natural frequency of the oscillators, which
      allows the responses to last much longer than the oscillation period of the
      oscillators. We can control the response duration by tuning the connection
      strengths between the oscillators and the external signal that triggers the
      responses. It is possible to break and restart the responses regardless of the
      way in which the oscillators are connected.

PMID- 22155989
TI  - Fair-view image reconstruction with dual dictionaries.
AB  - In this paper, we formulate the problem of computed tomography (CT)under sparsity
      and few-view constraints, and propose a novel algorithm for image reconstruction
      from few-view data utilizing the simultaneous algebraic reconstruction technique
      (SART) coupled with dictionary learning, sparse representation and total
      variation (TV) minimization on two interconnected levels. The main feature of our
      algorithm is the use of two dictionaries: a transitional dictionary for atom
      matching and a global dictionary for image updating. The atoms in the global and
      transitional dictionaries represent the image patches from high-quality and low
      quality CT images, respectively.Experiments with simulated and real projections
      were performed to evaluate and validate the proposed algorithm. The results
      reconstructed using the proposed approach are significantly better than those
      using either SART or SART-TV.

PMID- 22155990
TI  - Magnetic structure of CuCrO2: a single crystal neutron diffraction study.
AB  - This paper presents results of a recent study of multiferroic CuCrO(2) by means
      of single crystal neutron diffraction. This system has two close magnetic phase
      transitions at T(N) = 24.2 K and T(mf) = 23.6 K. The low temperature magnetic
      structure below T(mf) is unambiguously determined to be a fully three-dimensional
      proper screw. Between T(N) and T(mf) antiferromagnetic order is found that is
      essentially two-dimensional. In this narrow temperature range, magnetic near
      neighbor correlations are still long range in the (H,K) plane, whereas nearest
      neighbors along the L direction are uncorrelated. Thus, the multiferroic state is
      realized only in the low temperature three-dimensional state and not in the two
      dimensional state.

PMID- 22155991
TI  - Raman scattering in pathology.
AB  - Raman scattering is the inelastic scattering of light by chemical bonds, and can
      therefore show molecular specificity. It can be used both in pure spectroscopy
      mode, and in imaging mode. While many applications of Raman spectroscopy and
      imaging in the biomedical field have been so far demonstrated, the use of this
      technology for pathology applications is still in early stages. In this paper we
      review some of the most important recent developments in this field, including a
      description of relevant technologies, applications to molecular sensing,
      characterization of cells and tissues of interest, and disease detection via
      Raman scattering.

PMID- 22155993
TI  - Long-term survival after open repair and thoracic endovascular aortic repair for
      descending thoracic aortic aneurysms.

PMID- 22155992
TI  - A novel gene RNF138 expressed in human gliomas and its function in the glioma
      cell line U251.
AB  - BACKGROUND: The gliomas represent the most common primary malignant brain tumors;
      however, little is known about the molecular pathogenesis of these tumors. Recent
      research reveals that the oncogenesis and development of gliomas have a close
      relation to the overexpression of several oncogenes and the inactivation of tumor
      suppressor genes. Whether the RING finger protein, RNF138, a newly discovered
      protein, plays a role in glioma oncogenesis is unknown. The present study
      investigates the expression levels of RNF138 mRNA in glioma samples and
      noncancerous brain samples and its function in the human glioma cell line U251.
      METHODS: RT-PCR was used to ascertain the expression of RNF138 mRNA in the glioma
      cell lines U251, SHG44, U87, A172, and U373. The RNF138 mRNA expression levels of
      35 pathological confirmed glioma samples (Grade I - 4 cases, Grade II - 13 cases,
      Grade III - 11 cases, and Grade IV - 7 cases) and five noncancerous brain tissue
      samples were analyzed by real-time quantitative PCR. By RNA interference (RNAi)
      with the lentivirus vector system, the expression of RNF138 was inhibited in the
      human astrocytomas-glioblastoma multiforme cell line U251. The effects of RNF138
      knockdown on cell proliferation were assessed by Cellomics, and cell cycle and
      cell apoptosis were assessed by FACS. RESULTS: The RNF138 mRNA is expressed in
      the five glioma cell lines, and its expression level is significantly higher in
      glioma tissue than in noncancerous brain tissue. By down-regulation of RNF138
      expression, U251 cell proliferation was inhibited and cell apoptosis increased.
      At the same time, S stage cells lessened and G2 stage cells increased.
      CONCLUSION: The RNF138 gene is highly expressed in glioma tissue and glioma cell
      lines. It plays an important role in glioma cell proliferation, apoptosis, and
      cell cycle.

PMID- 22155994
TI  - Are improved results for hybrid repair of thoracoabdominal aortic aneurysms due
      to a learning curve or better patient selection?

PMID- 22155995
TI  - Acute coronary syndrome and khat herbal amphetamine use: an observational report.
AB  - BACKGROUND: The khat plant is a stimulant similar to amphetamine and is thought
      to induce coronary artery spasm. Khat is widely chewed by individuals originating
      from the Horn of Africa and the Arabian Peninsula. The aim of this study was to
      evaluate the clinical characteristics and outcome of khat chewers presenting with
      acute coronary syndrome. METHODS AND RESULTS: From October 1, 2008, through June,
      30, 2009, 7399 consecutive patients with acute coronary syndrome were enrolled in
      the Second Gulf Registry of Acute Coronary Events (Gulf RACE-2). Nineteen percent
      of patients were khat chewers; 81% were not. Khat chewers were older, more often
      male, and less likely to have cardiovascular risk factors. Khat chewers were less
      likely to have a history of coronary artery disease and more likely to present
      late and to have higher heart rate and advanced Killip class on admission. Khat
      chewers were more likely to present with ST-segment-elevation myocardial
      infarction. Overall, khat chewers had higher risk of death, recurrent myocardial
      ischemia, cardiogenic shock, ventricular arrhythmia, and stroke compared with non
      khat chewers. After adjustment for baseline variability, khat chewing was found
      to be an independent risk factor of death and for recurrent ischemia, heart
      failure, and stroke. CONCLUSIONS: Our data confirm earlier observations of worse
      in-hospital outcome among acute coronary syndrome patients who chew khat. This
      worse outcome persists up to 1 year from the index event. This observational
      report underscores the importance of improving education concerning the
      cardiovascular risks of khat chewing.

PMID- 22155996
TI  - Rate control in atrial fibrillation: targets, methods, resynchronization
      considerations.

PMID- 22155997
TI  - Management of severe mitral stenosis during pregnancy.

PMID- 22155998
TI  - Cardiology patient page. Randomized, controlled trials.

PMID- 22155999
TI  - Pericardiocentesis from back under echographic guidance: an approach for
      posterior pericardial effusions.

PMID- 22156000
TI  - Ectopic fat depots and cardiovascular disease.

PMID- 22156003
TI  - Letter by Toska regarding article, "Biological basis of therapeutic
      lymphangiogenesis".

PMID- 22156004
TI  - Letter by Mokhles et al regarding article, "Prosthetic heart valve".

PMID- 22156005
TI  - Letter by Bastiaenen and Behr regarding article, "Early repolarization:
      electrocardiographic phenotypes associated with favorable long-term outcome".

PMID- 22156006
TI  - Chromosomal damage and polymorphisms of metabolic genes among 1, 3-butadiene
      exposed workers in a matched study in China.
AB  - 1, 3-Butadiene (BD) is a high-efficiency carcinogen in rodents and was classified
      as a human carcinogen in 2008 by the International Agency for Research on Cancer.
      However, its ability to induce genetic damage and the influence of metabolic
      polymorphisms to such damage in humans are both controversial claims. This study
      was conducted to investigate the relationships between exposure to BD, the
      polymorphisms of metabolic genes and the chromosomal damage in 45 pairs of
      occupationally exposed workers in a BD product workshop and matched control
      workers in an administrative office and circulatory water workshop in China.
      Exposure to BD was evaluated by personal sampling and stationary sampling.
      Different chromosomal damage endpoints in peripheral blood lymphocytes were
      determined using the cytokinesis-blocked micronucleus (CBMN) cytome assay;
      polymorphisms of metabolic genes [cytochrome P450 2E1 (CYP2E1), glutathione S
      transferases (GST) and microsomal epoxide hydrolase (mEH)] in BD-exposed group
      were detected by polymerase chain reaction (PCR) or PCR-restriction fragment
      length polymorphism analysis. The results show that the average BD measurements
      of the exposed group were significantly higher than those for the control group
      (a personal sampling and stationary sampling, respectively). The BD-exposed
      workers exhibited increased frequencies of micronuclei (MNi) (8.00 +/- 3.780/00
      versus 5.62 +/- 2.410/00) and nucleoplasmic bridges (NPBs) (2.58 +/- 2.790/00
      versus 1.13 +/- 1.340/00) and a decreased nuclear division index (2.20 +/- 0.14
      versus 2.35 +/- 0.27) when compared subjects in the control group. Meanwhile, BD
      exposed workers carrying CYP2E1 c1c2/c2c2 or mEH intermediate (I)/high (H) group
      had a significantly higher NPB frequency than those carrying CYP2E1 c1c1
      [frequency ratio (FR) = 2.60, 95% confidence interval (CI) 1.72-3.93; P < 0.0001)
      or the mEH low(S) group (FR = 2.06, 95% CI% 1.17-3.62; P < 0.05), respectively.
      Our study suggests that MNi and NPB frequency in CBMN cytome assay could be
      potential genotoxic biomarkers for BD exposure in humans. The polymorphism of
      CYP2E1 and mEH could also affect the chromosomal instability of BD workers.

PMID- 22156007
TI  - Adapted Choi response criteria for prediction of clinical outcome in locally
      advanced gastric cancer patients following preoperative chemotherapy.
AB  - BACKGROUND: Tumor response to chemotherapy has traditionally been assessed by
      using Response Evaluation Criteria in Solid Tumors (RECIST) based on changes in
      tumor size alone. However, adapted Choi criteria, which incorporate volumetric
      tumor attenuation in addition to tumor size, have been reported more predictive
      of chemotherapeutic efficacy than RECIST in some studies. PURPOSE: To examine the
      usefulness of adapted Choi criteria in predicting clinical survival in locally
      advanced gastric cancer patients treated with cytotoxic drugs. MATERIAL AND
      METHODS: A total of 48 histologically proven gastric cancer patients who received
      neoadjuvant chemotherapy and surgery were involved. Pre- and post-chemotherapy
      short-axis diameter and volumetric mean tumor attenuation of target lymph nodes
      on contrast-enhanced CT images were measured. Tumor response was assessed by
      using both RECIST and adapted Choi criteria, and was correlated with progression
      free survival (PFS) and overall survival (OS). RESULTS: Significant decrease was
      observed in the sum of short-axis diameters and tumor attenuation of metastatic
      lymph nodes between baseline and post-chemotherapy CT images. The inter-observer
      agreement for both parameters was good. The PFS and OS of 17 RECIST responders
      were identical with that of 28 adapted Choi responders (P = 0.855 and 0.913,
      respectively). PFS and OS of 31 RECIST non-responders were significantly
      prolonged compared to that of 20 adapted Choi non-responders (P = 0.018 and
      0.042, respectively). To the 11 RECIST stable disease (SD) but adapted Choi
      partial response (PR) patients, the PFS and OS were similar to the survival of 17
      RECIST PR patients (P = 0.785 and 0.838, respectively), but significantly
      prolonged compared to that of the 12 both RECIST and adapted Choi criteria SD
      patients (P < 0.001 and P = 0.004, respectively). CONCLUSION: Adapted Choi
      criteria might be helpful to predict PFS and OS in locally advanced gastric
      cancer patients following chemotherapy.

PMID- 22156008
TI  - Evaluation of diffusion parameters and T2 values of the masseter muscle during
      jaw opening, clenching, and rest.
AB  - BACKGROUND: Diffusion-weighted imaging (DWI) and diffusion-tensor imaging (DTI)
      can be used to evaluate changes that accompany skeletal muscle contraction.
      PURPOSE: To investigate whether jaw opening or closure affect the diffusion
      parameters of the masseter muscles (MMs). MATERIAL AND METHODS: Eleven healthy
      volunteers were evaluated. Diffusion-tensor images were acquired to obtain the
      primary (lambda(1)), secondary (lambda(2)), and tertiary eigenvalues (lambda(3)).
      We estimated these parameters at three different locations: at the level of the
      mandibular notch for the superior site, the level of the mandibular foramen for
      the middle site, and the root apex of the mandibular molars for the inferior
      site. RESULTS: Both lambda(2) and lambda(3) during jaw opening were significantly
      lower than that at rest at the superior (P = 0.006, P < 0.0001, respectively) and
      middle site (P = 0.004, P = 0.0001, respectively); however, the change in
      lambda(1) was not significant. At the lower site, no parameter was significantly
      different at rest and during jaw opening. There was no significant difference in
      T2 between at rest (40.3 +/- 4.4 ms) and during jaw opening (39.2 +/- 2.7 ms; P =
      0.12). The changes induced by jaw closure were marked at the inferior site. In
      the middle and inferior sites, the three eigenvalues were increased by jaw
      closure, and the changes in lambda(1) (P = 0.0145, P = 0.0107, respectively) and
      lambda(2) (P = 0.0003, P = 0.0001) were significant (especially lambda(2)).
      CONCLUSION: The eigenvalues for diffusion of the MM were sensitive to jaw
      position. The recruitment of muscle fibers, specific to jaw position, reflects
      the differences in changes in muscle diffusion parameters.

PMID- 22156009
TI  - Simultaneous bilateral contrast injection in computed tomography pulmonary
      angiography.
AB  - BACKGROUND: Computed tomography pulmonary angiography (CTPA) has evolved as the
      gold standard for diagnosing pulmonary embolism. However, subsegmental arteries
      are often not assessed to do insufficient attenuation. PURPOSE: To evaluate the
      influence of simultaneous bilateral versus unilateral injection of a fixed amount
      of contrast media on pulmonary artery opacification and image quality in CTPA.
      MATERIAL AND METHODS: In this institutional review board-approved prospective
      study, 180 patients (91 women, mean age 61.9 +/- 16.5 years) referred for CTPA
      (100 kV) due to suspected pulmonary embolism were randomized in groups of 45
      patients each, with either unilateral (A:4 mL/s; B:6 mL/s) or bilateral (C: 6
      mL/s; D: 8 mL/s) (Y-shaped line) injection of 50 mL contrast media. Attenuation
      was assessed including the subsegmental arteries (4th order). Image quality was
      evaluated by two readers in consensus using a three-point grading scale (3 =
      excellent image quality, no artifacts, 1 = non-diagnostic). RESULTS: Mean
      pulmonary artery attenuation was significantly higher with bilateral injection
      (1st to 3rd order: A: 303.6 +/- 8.8HU; B: 371.1 +/- 11.0HU vs. C: 443.2 +/-
      24.1HU; D: 562.3 +/- 15.3HU, P < 0.001). Evaluation of subsegmental arteries was
      feasible for all patients in groups B-D, but only in 36/45 (80%) patients in
      group A. Subsegmental attenuation was significantly higher with bilateral
      injection (A: 284.7 +/- 12.1HU; B: 367.4 +/- 12.1HU vs. C: 494.2 +/- 21.5HU; D:
      562.3 +/- 26.7HU, P < 0.001). Image quality was diagnostic for all patients but
      best for group C (A: 2.15 +/- 0.4; B: 2.14 +/- 0.5; C: 2.92 +/- 0.3, and D: 2.51
      +/- 0.5). CONCLUSION: Using the same amount of contrast media, bilateral
      injection yields higher pulmonary artery attenuation and better image quality
      than unilateral injection. This technique may improve subsegmental pulmonary
      artery assessment.

PMID- 22156010
TI  - Association between cerebral microbleeds and the first onset of intracerebral
      hemorrhage - a 3.0 T MR study.
AB  - BACKGROUND: Cerebral microbleeds (CMBs) detected by gradient-echo MRI have been
      proven to be a potential risk factor for further bleeding, while the association
      between CMBs and the first onset of intracerebral hemorrhage has not been well
      investigated. PURPOSE: To analyze the association between CMBs and the first
      onset of primary intracerebral hemorrhage (pICH). MATERIAL AND METHODS: Two
      hundred and two consecutive inpatients with ICH and 234 consecutive outpatients
      without ICH as control group were enrolled in this study. MR imaging including
      T2*-GRE, T(1)W, T(2)W and fluid attenuated inversion recovery (FLAIR) sequences
      were performed to detect CMBs and other abnormalities. Prevalence, distribution,
      and grades of CMBs, as well as the location and size of the intracerebral
      hematoma were analyzed, respectively. Comparison was made between pICH and
      control group. Logistic analysis was performed to evaluate the association
      between CMBs and ICH. The correlation between hematoma size and CMBs
      grade/numbers was analyzed. RESULTS: CMBs were detected in 140 patients in pICH
      (69.3%) group and 62 patients in control group (26.5%). The incidence of CMBs in
      pICH group was significantly higher than that in control group (P < 0.0001). As
      the logistic regression analysis results, CMBs was the risk factor associated
      with ICH, with modulation OR value of 8.363 (95% CI 5.210-13.421). The volume of
      ICH with CMBs was 12.57 +/- 17.23 mL, and the volume of ICH without CMBs was
      17.77 +/- 26.97 mL. Negative correlation was demonstrated between CMBs number and
      ICH volume (r(s) = -0.1769, P = 0.0118), as well as between CMBs grade and
      hematoma volume (r(s) = -0.1185, P = 0.1557). CONCLUSION: CMBs may be an
      independent risk factor for the first onset of intracerebral hemorrhage.

PMID- 22156011
TI  - A novel compensation method for the anode gain non-uniformity of multi-anode
      photomultiplier tubes.
AB  - The position-sensitive multi-anode photomultiplier tube (MA-PMT) is widely used
      in high-resolution scintillation detectors. However, the anode gain nonuniformity
      of this device is a limiting factor that degrades the intrinsic performance of
      the detector module. The aim of this work was to develop a gain compensation
      method for the MA-PMT and evaluate the resulting enhancement in the performance
      of the detector. The method employs a circuit that is composed only of resistors
      and is placed between the MA-PMT and a resistive charge division network (RCN)
      used for position encoding. The goal of the circuit is to divide the output
      current from each anode, so the same current flows into the RCN regardless of the
      anode gain. The current division is controlled by the combination of a fixed
      value series resistor with an output impedance that is much larger than the input
      impedance of the RCN, and a parallel resistor, which detours part of the current
      to ground. PSpice simulations of the compensation circuit and the RCN were
      performed to determine optimal values for the compensation resistors when used
      with Hamamatsu H8500 MAPMTs. The intrinsic characteristics of a detector module
      consisting of this MA-PMT and a lutetium-gadolinium-oxyorthosilicate (LGSO)
      crystal array were tested with and without the gain compensation method. In
      simulation, the average coefficient of variation and max/min ratio decreased from
      15.7% to 2.7% and 2.0 to 1.2, respectively. In the flood map of the LGSO-H8500
      detector, the uniformity of the photopeak position for individual crystals and
      the energy resolution were much improved. The feasibility of the method was shown
      by applying it to an octagonal prototype positron emission tomography scanner.

PMID- 22156012
TI  - Stone-Wales defects can cause a metal-semiconductor transition in carbon
      nanotubes depending on their orientation.
AB  - It has been shown that the two different orientations of Stone-Wales (SW)
      defects, i.e. longitudinal and circumferential SW defects, on carbon nanotubes
      (CNTs) result in two different electronic structures. Based on density functional
      theory we have shown that the longitudinal SW defects do not open a bandgap near
      the Fermi energy, while a relatively small bandgap emerges in tubes with
      circumferential defects. We argue that the bandgap opening in the presence of
      circumferential SW defects is a consequence of long-range symmetry breaking which
      can spread all the way along the tube. Specifically, the distribution of
      contracted and stretched bond lengths due to the presence of defects, and hopping
      energies for low-energy electrons, i.e. the 2p(z) electrons, show two different
      patterns for the two types of defects. Interplay between the geometric features
      and the electronic properties of the tubes have also been studied for different
      defect concentrations. Considering pi-orbital charge density, it has also been
      shown that the deviations of bond lengths from their relaxed length result in
      different doping for two defect orientations around the defects-electron-rich for
      a circumferential defect and hole-rich for a longitudinal one. We have also shown
      that, in the tubes having both types of defects, circumferential defects would
      dominate and impose their electronic properties.

PMID- 22156013
TI  - Fabrication of vertically stacked single-crystalline Si nanowires using self
      limiting oxidation.
AB  - A simple method for fabricating vertically stacked single-crystal silicon
      nanowires on standard bulk silicon wafers is presented. The process uses
      inductively coupled plasma (ICP) etching to create silicon fins with uneven yet
      controllable vertical profiles. The fins are then thermally oxidized in a self
      limiting process, and the narrow regions are completely consumed to create
      multiple nanowires vertically stacked on each other. It was found that the number
      of nanowires in the vertical stack depends on the number of ICP cycles. A
      mechanism for the formation of the nanowires is proposed and confirmed with
      numerical simulations.

PMID- 22156014
TI  - Biomimetic surface modification of titanium surfaces for early cell capture by
      advanced electrospinning.
AB  - The time required for osseointegration with a metal implant having a smooth
      surface ranges from three to six months. We hypothesized that biomimetic coating
      surfaces with poly(lactic-co-glycolic acid) (PLGA)/collagen fibers and nano
      hydroxyapatite (n-HA) on the implant would enhance the adhesion of mesenchymal
      stem cells. Therefore, this surface modification of dental and bone implants
      might enhance the process of osseointegration. In this study, we coated PLGA or
      PLGA/collagen (50:50 w/w ratio) fiber on Ti disks by modified electrospinning for
      5 s to 2 min; after that, we further deposited n-HA on the fibers. PLGA fibers of
      fiber diameter 0.957 +/- 0.357 um had a contact angle of 9.9 +/- 0.3 degrees  and
      PLGA/collagen fibers of fiber diameter 0.378 +/- 0.068 um had a contact angle of
      0 degrees . Upon n-HA incorporation, all the fibers had a contact angle of 0
      degrees  owing to the hydrophilic nature of n-HA biomolecule. The cell attachment
      efficiency was tested on all the scaffolds for different intervals of time (10,
      20, 30 and 60 min). The alkaline phosphatase activity, cell proliferation and
      mineralization were analyzed on all the implant surfaces on days 7, 14 and 21.
      Results of the cell adhesion study indicated that the cell adhesion was maximum
      on the implant surface coated with PLGA/collagen fibers deposited with n-HA
      compared to the other scaffolds. Within a short span of 60 min, 75% of the cells
      adhered onto the mineralized PLGA/collagen fibers. Similarly by day 21, the rate
      of cell proliferation was significantly higher (p ? 0.05) on the mineralized
      PLGA/collagen fibers owing to enhanced cell adhesion on these fibers. This
      enhanced initial cell adhesion favored higher cell proliferation, differentiation
      and mineralization on the implant surface coated with mineralized PLGA/collagen
      fibers.

PMID- 22156015
TI  - CD133 expression and identification of CD133/nestin positive cells in
      rhabdomyosarcomas and rhabdomyosarcoma cell lines.
AB  - BACKGROUND: Co-expression of CD133, cell surface glycoprotein, and nestin, an
      intermediate filament protein, was determined to be a marker of neural stem cells
      and of cancer stem cells in neurogenic tumors. METHODS: We examined the
      expression of CD133 and nestin in ten tumor tissue samples taken from patients
      with rhabdomyosarcomas and in five rhabdomyosarcoma cell lines.
      Immunohistochemistry and immunofluorescence were used to examine FFPE tumor
      tissue samples. Cell lines were analyzed by immunofluorescence, immunoblotting,
      flow cytometry, and RT-PCR. Functional assays (clonogenic in vitro assay and
      tumorigenic in vivo assay) were also performed using these cell lines. RESULTS:
      CD133 and nestin were detected in all 10 tumor tissue samples and in all 5 cell
      lines; however, the frequency of CD133+, Nes+, and CD133+/Nes+ cells, as well as
      the intensity of fluorescence varied in individual samples or cell lines. The
      expression of CD133 and nestin was subsequently confirmed in all cell lines by
      immunoblotting. Furthermore, we observed an increasing expression of CD133 in
      relation to the cultivation. All cell lines were positive for Oct3/4 and
      nucleostemin; NSTS-11 cells were also able to form xenograft tumors in mice.
      CONCLUSION: Our results represent the first evidence of CD133 expression in
      rhabdomyosarcoma tissue and in rhabdomyosarcoma cell lines. In addition, the co
      expression of CD133 and nestin as well as results of the functional assays
      suggest a possible presence of cancer cells with a stem-like phenotype in these
      tumors.

PMID- 22156016
TI  - Differential signature of the centrosomal MARK4 isoforms in glioma.
AB  - BACKGROUND: MAP/microtubule affinity-regulating kinase 4 (MARK4) is a serine
      threonine kinase expressed in two spliced isoforms, MARK4L and MARK4S, of which
      MARK4L is a candidate for a role in neoplastic transformation. METHODS: We
      performed mutation analysis to identify sequence alterations possibly affecting
      MARK4 expression. We then investigated the MARK4L and MARK4S expression profile
      in 21 glioma cell lines and 36 tissues of different malignancy grades,
      glioblastoma-derived cancer stem cells (GBM CSCs) and mouse neural stem cells
      (NSCs) by real-time PCR, immunoblotting and immunohistochemistry. We also
      analyzed the sub-cellular localisation of MARK4 isoforms in glioma and normal
      cell lines by immunofluorescence. RESULTS: Mutation analysis rules out sequence
      variations as the cause of the altered MARK4 expression in glioma. Expression
      profiling confirms that MARK4L is the predominant isoform, whereas MARK4S levels
      are significantly decreased in comparison and show an inverse correlation with
      tumour grade. A high MARK4L/MARK4S ratio also characterizes undifferentiated
      cells, such as GBM CSCs and NSCs. Accordingly, only MARK4L is expressed in brain
      neurogenic regions. Moreover, while both MARK4 isoforms are localised to the
      centrosome and midbody in glioma and normal cells, the L isoform exhibits an
      additional nucleolar localisation in tumour cells. CONCLUSIONS: The observed
      switch towards MARK4L suggests that the balance between the MARK4 isoforms is
      carefully guarded during neural differentiation but may be subverted in
      gliomagenesis. Moreover, the MARK4L nucleolar localisation in tumour cells
      features this MARK4 isoform as a nucleolus-associated tumour marker.

PMID- 22156018
TI  - Comprehensive evaluation of the impact of 14 genetic variants on colorectal
      cancer phenotype and risk.
AB  - To comprehensively evaluate the impact of recently identified colorectal cancer
      (CRC) variants at 1q41, 3q26.2, 8q23.3, 8q24.21, 10p14, 11q23.1, 12q13.13,
      14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12.3, and 20q13.33 on risk and
      CRC phenotype, the authors analyzed 8,878 cases and 6,051 controls from the
      United Kingdom ascertained in 1999-2007. The impact of variants on the familial
      CRC risk was enumerated from age-, sex-, and calendar-specific CRC rates in the
      50,924 first-degree relatives of cases. Each of the 14 susceptibility loci
      independently influences CRC with the risk increasing with increasing number of
      risk alleles carried (per allele odds ratio = 1.13; P = 2.99 * 10(-58)) and, for
      those within the upper quintile, there is a 2.3-fold increased risk. In first
      degree relatives of cases with <=17, 18-21, and >=22 risk alleles, standardized
      incidence ratios were 1.76, 2.08, and 2.25, respectively. Although the
      discriminatory attributes of the 14 CRC susceptibility loci for individual risk
      prediction are poor (area under the curve = 0.58), they may allow subgroups of
      the population at different CRC risks to be distinguished.

PMID- 22156020
TI  - Re: "From emergence to eradication: the epidemiology of poliomyelitis
      deconstructed".

PMID- 22156019
TI  - Environmental and urinary markers of prenatal exposure to drinking water
      disinfection by-products, fetal growth, and duration of gestation in the PELAGIE
      birth cohort (Brittany, France, 2002-2006).
AB  - Although prenatal exposure to water disinfection by-products does not appear to
      affect the duration of gestation, its impact on fetal growth remains an open
      question. The authors studied the associations between prenatal exposure to
      disinfection by-products and fetal growth restriction (FGR) and preterm birth in
      the PELAGIE cohort, a French birth cohort comprising 3,421 pregnant women
      recruited between 2002 and 2006. Exposure was assessed by estimating levels of
      trihalomethanes (THMs) in tap water during pregnancy and maternal water use and
      by measuring maternal urinary levels of trichloroacetic acid (TCAA) during early
      pregnancy in a nested case-control design that compared 174 FGR cases, 114
      preterm births, and 399 controls. Higher uptake of THMs (especially brominated
      THMs) was associated with a higher risk of FGR. Women with TCAA detected in their
      urine (>0.01 mg/L) had a higher risk of FGR than those with TCAA levels below the
      detection limit (adjusted odds ratio = 1.8, 95% confidence interval: 0.9, 3.7)
      and had an odds ratio for preterm birth below 1 (adjusted odds ratio = 0.8, 95%
      confidence interval: 0.3, 2.6). Results from this prospective study, the first to
      use a biomarker of disinfection by-product exposure, suggest that prenatal
      exposure affects fetal growth, but the causal agent or agents remain to be
      identified.

PMID- 22156021
TI  - Invited commentary: biomarkers of exposure to drinking water disinfection by
      products--are we ready yet?
AB  - Studies of the relation between exposure to drinking water disinfection by
      products and pregnancy outcomes have been limited by the complexity of the
      exposure itself (consisting of hundreds of different chemicals), the diverse
      pathways contributing to exposure, and the difficulty in assessing behavioral
      determinants of exposure. Therefore, exposure biomarkers offer great promise of
      enhancing exposure assessment, the limiting factor in the quality and
      conclusiveness of epidemiologic studies. However, there are significant
      conceptual and logistical challenges in developing biomarkers for the various
      constituents of concern that are sensitive to typical variation in exposure,
      reflective of the time periods of interest, not susceptible to interference from
      exposures other than water, not subject to reverse causality by correlates of
      adverse pregnancy outcomes, reflective of the chemicals of interest, and feasible
      for large-scale epidemiologic studies. Urinary trichloroacetic acid has been the
      leading candidate exposure biomarker for over a decade, and the first attempt to
      incorporate it into an epidemiologic study (Am J Epidemiol. 2012;175(4):263-275)
      is notable-the considerable limitations notwithstanding. In future efforts,
      investigators need to combine biomarker development with substantive
      epidemiologic studies to improve on this initial effort and prepare for more
      definitive research.

PMID- 22156022
TI  - Monte Carlo simulation of energy-deposit clustering for ions of the same LET in
      liquid water.
AB  - This work presents a Monte Carlo study of energy depositions due to protons,
      alpha particles and carbon ions of the same linear-energy-transfer (LET) in
      liquid water. The corresponding track structures were generated using the Geant4
      DNA toolkit, and the energy deposition spatial distributions were analyzed using
      an adapted version of the DBSCAN clustering algorithm. Combining the Geant4
      simulations and the clustering algorithm it was possible to compare the quality
      of the different radiation types. The ratios of clustered and single energy
      depositions are shown versus particle LET and frequency-mean lineal energies. The
      estimated effect of these types of radiation on biological tissues is then
      discussed by comparing the results obtained for different particles with the same
      LET.

PMID- 22156023
TI  - Incommensurate magnetic order in TbTe3.
AB  - We report a neutron diffraction study of the magnetic phase transitions in the
      charge-density wave (CDW) TbTe(3) compound. We discover that in the paramagnetic
      phase there are strong 2D-like magnetic correlations, consistent with the
      pronounced anisotropy of the chemical structure. A long-range incommensurate
      magnetic order emerges in TbTe(3) at T(mag1) = 5.78 K as a result of continuous
      phase transitions. We observe that near the temperature T(mag1) the magnetic
      Bragg peaks appear around the position (0, 0, 0.24) (or its rational multiples),
      that is fairly close to the propagation vector (0,0,0.29) associated with the CDW
      phase transition in TbTe(3). This suggests that correlations leading to the long
      range magnetic order in TbTe(3) are linked to the modulations that occur in the
      CDW state.

PMID- 22156024
TI  - Nanospace engineering of KOH activated carbon.
AB  - This paper demonstrates that nanospace engineering of KOH activated carbon is
      possible by controlling the degree of carbon consumption and metallic potassium
      intercalation into the carbon lattice during the activation process. High
      specific surface areas, porosities, sub-nanometer (<1 nm) and supra-nanometer (1
      5 nm) pore volumes are quantitatively controlled by a combination of KOH
      concentration and activation temperature. The process typically leads to a
      bimodal pore size distribution, with a large, approximately constant number of
      sub-nanometer pores and a variable number of supra-nanometer pores. We show how
      to control the number of supra-nanometer pores in a manner not achieved
      previously by chemical activation. The chemical mechanism underlying this control
      is studied by following the evolution of elemental composition, specific surface
      area, porosity, and pore size distribution during KOH activation and preceding
      H(3)PO(4) activation. The oxygen, nitrogen, and hydrogen contents decrease during
      successive activation steps, creating a nanoporous carbon network with a porosity
      and surface area controllable for various applications, including gas storage.
      The formation of tunable sub-nanometer and supra-nanometer pores is validated by
      sub-critical nitrogen adsorption. Surface functional groups of KOH activated
      carbon are studied by microscopic infrared spectroscopy.

PMID- 22156025
TI  - Addressing the nonexercise part of the activity continuum: a more realistic and
      achievable approach to activity programming for adults with mobility disability?
AB  - Participation in physical activity is fundamental for the maintenance of
      metabolic health and the prevention of major chronic diseases, particularly type
      2 diabetes and cardiovascular disease. A whole-of-day approach to physical
      activity promotion is increasingly advocated and includes not only increasing
      moderate-intensity physical activity but also reducing sedentary time and
      increasing light-intensity activity (the "nonexercise" part of the activity
      continuum). This whole-of-day approach to tackling the challenge of inactivity
      may be particularly relevant for adults with mobility disabilities, who are among
      the most inactive segment of the population. Focusing on nonexercise activity by
      striving to reduce sedentary time and increase light-intensity activity may be a
      more successful place to begin to change behavior in someone with mobility
      disability. This article discusses what is known about the metabolic health
      consequences of sedentary behavior and light-intensity activity in adults with
      and without mobility disability. The concept of inactivity physiology is
      presented, along with possible applications or evidence from studies with adults
      with mobility disability. Mobility disability discussions and examples focus on
      stroke and spinal cord injury. Finally, clinical implications and future research
      directions related to sedentary behavior in adults with mobility disability are
      discussed.

PMID- 22156026
TI  - Factors that affect decisions about physical activity and exercise in survivors
      of breast cancer: a qualitative study.
AB  - BACKGROUND: Exercise has many benefits for survivors of breast cancer, yet only
      half of this population regularly exercise. Fear has been identified as a barrier
      to exercise for people with neuromusculoskeletal conditions but has been
      minimally explored in women with breast cancer. OBJECTIVES: The purposes of this
      study were: (1) to investigate factors that affected decisions about physical
      activity and exercise in survivors of breast cancer and (2) to determine whether
      fear was a factor. DESIGN: This investigation was a grounded-theory qualitative
      study. Qualitative data were triangulated with data from 2 quantitative scales
      that measured participants' beliefs about exercise and their activity levels.
      METHODS: Thirty-four survivors of breast cancer in 8 focus groups participated in
      semistructured interviews that were recorded, transcribed, and coded. Concept
      maps created for each group were merged to develop themes. Beliefs about physical
      activity and exercise were assessed with the Decisional Balance Scale. The Rapid
      Assessment of Physical Activity was used to assess behaviors regarding physical
      activity and exercise before and after the breast cancer diagnosis. RESULTS:
      Participants generally believed that exercise was beneficial (Decisional Balance
      Scale score: X=28.1 [of a maximum score of 44], SD=7.6, range=10-43).
      Participants decreased the amount of physical activity or exercise during
      treatment but increased the amount of exercise beyond prediagnosis levels after
      treatment (Rapid Assessment of Physical Activity score: median=6, range=2-7).
      Three prominent themes described participants' behaviors regarding physical
      activity or exercise: values and beliefs about exercise, facilitators and
      barriers that were both similar to those affecting the general population and
      cancer specific, and lack of or inaccurate information about safe exercise.
      CONCLUSIONS: Survivors who were active were not afraid to exercise. However,
      concern about lymphedema and knowledge about safe and effective exercise programs
      influenced choices regarding physical activity and exercise.

PMID- 22156027
TI  - Functional recovery of a patient with anorexia nervosa: physical therapist
      management in the acute care hospital setting.
AB  - BACKGROUND AND PURPOSE: People with severe, long-standing anorexia nervosa (AN)
      often develop physical manifestations of medical starvation. Functional deficits
      are not well described, and little information is available to guide physical
      intervention. This case report describes the physical therapy clinical decision
      making process and intervention provided to a patient with severe AN. CASE
      DESCRIPTION: The patient was a 48-year-old woman admitted to an acute care
      hospital with medical complications associated with AN and requiring medical
      stabilization. On admission, she was unable to complete basic functional
      activities (eg, bed mobility, transfers, ambulation). She was considered at risk
      for falls, with a score of 17 on the Performance-Oriented Motor Assessment (POMA)
      and a score of 19.27 seconds on the Timed "Up & Go" Test (TUG). Physical
      therapist examination and intervention focused on functional testing and
      training, strengthening, and postural stability training for return to
      independence. OUTCOMES: In 9 weeks, the patient returned to independence in basic
      activities of daily living, as measured by 3 items from the motor domain (bed
      mobility, transfers, and ambulation) of the Functional Independence Measure, with
      improvements from 1 ("total assistance") to 6 ("modified independence") on each
      item. Postural stability improved to "low risk" for falls (POMA score of 24). Her
      TUG score improved to 11.00 seconds. Walking speed improved from 0.35 to 0.81
      m/s. Once she attained medical stability, she was discharged home with her
      parents with outpatient services. DISCUSSION: Physical therapist management of
      this severely deconditioned patient hospitalized with severe AN focused on the
      restoration of functional activities, with intervention intensity being guided by
      physiologic responses. Traditional aerobic and endurance training were de
      emphasized to minimize kilocalorie expenditure and tendencies toward exercise
      compulsion in this patient population.

PMID- 22156028
TI  - Feasibility and validity of a graded one-legged cycle exercise test to determine
      peak aerobic capacity in older people with a lower-limb amputation.
AB  - BACKGROUND: Information concerning exercise tolerance and aerobic capacity is
      imperative for generating effective and safe exercise programs. However, for
      older people with a lower-limb amputation, a standard exercise test is not
      available. OBJECTIVE: The primary aim of the present study was to determine
      whether a graded 1-legged peak exercise test is feasible and provides a valid
      assessment of peak aerobic capacity in older people walking with a lower-limb
      prosthesis. DESIGN: This was a quasi-experimental case-control study. METHODS: A
      total of 36 older people with a lower-limb prosthesis and 21 people who were able
      bodied (controls) (overall mean age=61.7 years, SD=6.1) performed a discontinuous
      graded 1-legged exercise test. The peak respiratory exchange ratio was used as an
      indicator of maximal effort. The controls performed an additional 2-legged
      exercise test to provide insight into differences between the testing modes.
      RESULTS: All participants were able to perform the exercise test.
      Electrocardiographic tracings and blood pressure were adequately monitored. The
      controls and the people with a lower-limb amputation were able to stress the
      cardiovascular system to a similar extent. Analyses of construct validity
      revealed that the peak aerobic capacity measured with the 1-legged exercise test
      was able to distinguish between participants on the basis of age, body mass
      index, and sex to a similar extent as the conventional 2-legged exercise test.
      LIMITATIONS: The results can be generalized only to people who are able to
      ambulate with their prosthesis. CONCLUSIONS: The graded 1-legged exercise test
      was feasible and provided a valid assessment of peak aerobic capacity and
      exercise tolerance in older people walking with a lower-limb prosthesis.

PMID- 22156029
TI  - Toward smarter BCIs: extending BCIs through hybridization and intelligent
      control.
AB  - This paper summarizes two novel ways to extend brain-computer interface (BCI)
      systems. One way involves hybrid BCIs. A hybrid BCI is a system that combines a
      BCI with another device to help people send information. Different types of
      hybrid BCIs are discussed, along with challenges and issues. BCIs are also being
      extended through intelligent systems. Software that allows high-level control,
      incorporates context and the environment and/or uses virtual reality can
      substantially improve BCI systems. Throughout the paper, we critically address
      the real benefits of these improvements relative to existing technology and
      practices. We also present new challenges that are likely to emerge as these
      novel BCI directions become more widespread.

PMID- 22156030
TI  - Improvement of the microcirculation in the acute ischemic rat limb during
      intravenous infusion of drag-reducing polymers.
AB  - Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase
      blood flow and reduce vascular resistance. The purpose of the present study is to
      examine the effects of DRPs on microcirculation in rat hind limb during acute
      femoral artery occlusion. Two groups of 20 male Wistar rats were subjected to
      either hemodynamic measurement or contrast enhanced ultrasound (CEU) imaging
      during peripheral ischemia. Both groups were further subdivided into a DRP
      treated group or a saline-treated group. Polyethylene oxide (PEO) was chosen as
      the test DRP, and rats were injected with either 10 ppm PEO solution or saline
      through the caudal vein at a constant rate of 5 ml/h for 20 min. Abdominal aortic
      flow, iliac artery pressure, iliac vein pressure, heart rate, carotid artery
      pressure and central venous pressure (CVP) were monitored, and vascular
      resistance was calculated by (iliac artery pressure-iliac vein
      pressure)/abdominal aortic blood flow. Flow perfusion and capillary volume of
      skeletal muscle were measured by CEU. During PEO infusion, abdominal aortic blood
      flow increased (p<0.001) and vascular resistance decreased (p<0.001) compared to
      rats that received saline during peripheral ischemia. There was no significant
      change in ischemic skeletal capillary volume (A) with DRP treatment (p>0.05), but
      red blood cell velocity (beta) and capillary blood flow (A*beta) increased
      significantly (p<0.05) during PEO infusion. In addition, A, beta and A*beta all
      increased (p<0.05) in the contralateral hind limb muscle. In contrast, PEO had no
      significant influence on heart rate, mean carotid artery blood pressure or CVP.
      Intravenous infusion of drag reducing polymers may offer a novel hydrodynamic
      approach for improving microcirculation during acute peripheral ischemia.

PMID- 22156031
TI  - Viscoelastic properties of blood studied through piezoresistance measurements.
AB  - Piezoresistance describes the change of electrical resistance in a material
      undergoing deformation. Heterogeneous materials having different resistivities of
      dispersed and continuous matrix phases, such as blood (comprised of red and white
      blood cells and platelets suspended in plasma), can exhibit the piezoresistance
      effect. For an initially isotropic material, two independent intrinsic material
      coefficients, lambda1 and lambda2, would uniquely describe the piezoresistance
      phenomenon. Materials undergoing deformation affect a material's resistivity in
      two ways: (a) by introducing anisotropy in the material, which is characterized
      by lambda1 and (b) by changing the volume density of the inclusions, which is
      associated with (1/3 lambda1+lambda2). In this paper, the piezoresistance effect
      in bovine blood samples is studied under oscillatory shear flow with a planar
      sensor rosette. The first piezoresistance coefficient, lambda1, was measured at
      various frequencies and shear rates in the blood flow and compared with cos delta
      (equal to G'/G*, where G' and G* are the storage and complex moduli,
      respectively), which reflects the degree of elasticity. The coefficient lambda1
      was found to have a trend similar to that of cos delta under all conditions
      tested. Thus lambda1 might potentially be used to characterize the viscoelastic
      properties of blood and the deformability of red blood cells, thus clarifying
      pathophysiology and facilitating diagnosis.

PMID- 22156032
TI  - Effect of lanthanides on red blood cell deformability and response to mechanical
      stress: role of lanthanide ionic radius.
AB  - Prior studies exploring the effects of lanthanides (Ln) on red blood cells (RBC)
      have primarily focused on ion transport, cell fusion, and membrane protein
      structure. Our previous report [Biorheology 44 (2007), 361-373] dealt only with
      lanthanum (La) and cell rigidity; the present study extends these observations to
      other lanthanides (Nd, Sm, Eu, Dy, Er) and to RBC response to mechanical shear.
      Deformation-shear stress behavior of normal human RBC was measured at Ln
      concentrations up to 200 MUM. In another series of experiments, RBC were exposed
      to mechanical stress (190 Pa, 300 s) at 50 MUM Ln and deformation-stress data
      obtained prior to and after this stress. Data were fitted to a Lineweaver-Burke
      model to obtain the shear stress at one-half maximum deformation (SS1/2). Our
      results include: (1) lanthanides cause decreased cell deformability with the
      magnitude of the decrease dependent on concentration and shear stress; (2) this
      decrease of deformability is affected by Ln ionic radius such that
      La>Nd>Sm>Eu>Dy>Er and is reversible for cells in Ln-free media; (3) mechanical
      stress decreases deformability (i.e., increases SS1/2) such that compared to
      control, La and Sm reduce and Dy and Er enhance the mechanical stress effect; (4)
      the decrease of deformability consequent to mechanical stress scales inversely
      with Ln ionic radius. These results indicate a reciprocal relation between cell
      rigidity and sensitivity to mechanical stress that is mediated by Ln ionic
      radius. Additional studies are clearly warranted, particularly those that explore
      membrane-glycocalyx and intracellular mechanisms.

PMID- 22156033
TI  - Lattice Boltzmann simulations of the time evolution of living multicellular
      systems.
AB  - Embryonic tissues and multicellular aggregates of adult cells mimic the behavior
      of highly viscous liquids. The liquid analogy helps to understand morphogenetic
      phenomena, such as cell sorting and tissue fusion, observed in developmental
      biology and tissue engineering. Tissue fusion is vital in tissue printing, an
      emergent technique based on computer-controlled deposition of tissue fragments
      and biocompatible materials. Computer simulations proved useful in predicting
      post-printing shape changes of tissue constructs. The simulation methods
      available to date, however, are unable to describe the time evolution of living
      systems made of millions of cells. The Lattice Boltzmann (LB) approach allows the
      implementation of interaction forces between the constituents of the system and
      yields time evolution in terms of distribution functions. With tissue engineering
      applications in mind, we have developed a finite difference Lattice Boltzmann
      model of a multicellular system and applied it to simulate the sidewise fusion of
      two contiguous cylinders made of cohesive cells and embedded in a medium
      (hydrogel). We have identified a biologically relevant range of model parameters.
      The proposed LB model may be extended to describe the time evolution of more
      complex multicellular structures such as sheets or tubes produced by tissue
      printing.

PMID- 22156034
TI  - Effects of transients on pulsatile flow in arteries.
AB  - Analytical solutions to the model problem of unsteady Newtonian fluid flow in
      straight, elastic-walled vessels can provide: theoretical insights into the flow
      of blood in arteries; a theoretical basis for clinical measurements in diagnoses
      of arterial flow rates; and guidance for boundary conditions in numerical
      simulations of flow in finite computational domains. However, while Womersley's
      analyses of blood flow assume solution forms that treat the flow as periodic and
      continuously unsteady, many flow variables in the smaller arteries are not
      continuously unsteady at all. They are characterized more accurately as rapid
      transient motions followed by a period of recovery to a stationary state,
      repeated in successive cycles. These flows are not continually unsteady ones
      described by Womersley's solutions but unsteady flows restarted from rest in each
      cycle, characterized as initial-boundary value problems. In this paper, we
      compare the Womersley and initial-boundary value solutions for model transients
      that stop then restart, explain these previously unreported limitations of
      Womersley's solutions, and demonstrate how the initial-boundary value solutions
      provide excellent agreement with measurements of blood flow in the anterior
      tibial and popliteal arteries of patients. Some consequences of these findings
      for understanding and interpreting measurements of blood flow, and for
      prescribing boundary conditions in computer simulations of arterial blood flow
      are discussed.

PMID- 22156035
TI  - Using a blood pressure harmonic variability index to monitor the cerebral blood
      flow condition in stroke patients.
AB  - OBJECTIVE: Beat-to-beat cardiovascular variability analysis provides important
      information on the autonomic control. Bilateral radial arterial blood pressure
      waveforms (BPW) in stroke patients were compared to explore the efficacy of
      frequency-domain variability index in evaluating bilateral differences in the
      cerebral blood-flow condition. METHODS: Five-minute BPW signals were obtained in
      22 stroke patients (Group S) and 21 healthy volunteers (control Group C).
      Amplitude proportions of the acquired pulses and their coefficient of variance
      (CVn) were calculated for 1st-10th harmonics to evaluate the blood pressure
      harmonic variability (BPHV). RESULTS: In Group S, CV1-CV7 were significantly
      larger on the stroke side than on the contralateral side. CV1, CV3-CV5 and CV7
      were significantly larger on the stroke side in Group S than on either side in
      Group C. CONCLUSIONS: We first demonstrate the feasibility of using BPHV index to
      noninvasively detect the bilateral difference in cerebral vascular resistance in
      stroke patients. Two main indexes could be developed based on the present
      results: (1) bilateral differences in BPHV in stroke patients; (2) BPHV
      differences between normal and stroke subjects. It might have meaning in
      developing an easy-to-perform, noninvasive and continuous monitoring technique to
      improve the early detection and disease progress monitoring for stroke.

PMID- 22156036
TI  - Linear shear response of the upper skin layers.
AB  - This study presents an in vitro experimental method to determine shear properties
      of the epidermis. Shear tests were performed with a parallel plate rheometer on
      samples of stratum corneum and the viable epidermis. The method was validated on
      very thin silicon sheets. Preliminary test were performed to determine the linear
      viscoelastic range, the effect of normal loading on the sample and the time to
      reach equilibrium after changes of temperature and relative humidity. The study
      shows that reproducible results can be obtained for the shear properties of
      epidermis in an in vitro set up. The dynamic shear modulus for stratum corneum
      ranges from about 4-12 kPa, decreasing with increasing relative humidity. The
      values are considerably lower than the shear modulus value based on tensile
      Young's moduli in the literature, indicating a considerable anisotropic material
      behavior. Results for the epidermis were of the same order of magnitude, but were
      less consistent possibly due to a less well-defined tissue composition.

PMID- 22156037
TI  - Use of risk scores in acute coronary syndromes.

PMID- 22156038
TI  - Incorporation of diffusion-weighted magnetic resonance imaging data into a simple
      mathematical model of tumor growth.
AB  - We build on previous work to show how serial diffusion-weighted MRI (DW-MRI) data
      can be used to estimate proliferation rates in a rat model of brain cancer.
      Thirteen rats were inoculated intracranially with 9L tumor cells; eight rats were
      treated with the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea and
      five rats were untreated controls. All animals underwent DW-MRI immediately
      before, one day and three days after treatment. Values of the apparent diffusion
      coefficient (ADC) were calculated from the DW-MRI data and then used to estimate
      the number of cells in each voxel and also for whole tumor regions of interest.
      The data from the first two imaging time points were then used to estimate the
      proliferation rate of each tumor. The proliferation rates were used to predict
      the number of tumor cells at day three, and this was correlated with the
      corresponding experimental data. The voxel-by-voxel analysis yielded Pearson's
      correlation coefficients ranging from -0.06 to 0.65, whereas the region of
      interest analysis provided Pearson's and concordance correlation coefficients of
      0.88 and 0.80, respectively. Additionally, the ratio of positive to negative
      proliferation values was used to separate the treated and control animals (p
      <0.05) at an earlier point than the mean ADC values. These results further
      illustrate how quantitative measurements of tumor state obtained non-invasively
      by imaging can be incorporated into mathematical models that predict tumor
      growth.

PMID- 22156039
TI  - Dispersive crystal field excitations and quadrupolar interactions in UPd3.
AB  - We report inelastic neutron scattering measurements and random phase
      approximation calculations of the dispersive crystal field excitations of UPd(3).
      The measured spectra at lower energies agree with those calculated using
      quadrupolar interaction parameters deduced from bulk and x-ray scattering
      measurements. The more intense excitations arising from the hexagonal sites were
      used to obtain exchange parameters which proved to be anisotropic.

PMID- 22156040
TI  - Stepwise motion of a microcantilever driven by the hydrolysis of viral ATPases.
AB  - The biomolecular machines involved in DNA packaging by viruses generate one of
      the highest mechanical powers observed in nature. One component of the DNA
      packaging machinery, called the terminase, has been proposed as the molecular
      motor that converts chemical energy from ATP hydrolysis into mechanical movement
      of DNA during bacteriophage morphogenesis. However, the conformational changes
      involved in this energy conversion have never been observed. Here we report a
      real-time measurement of ATP-induced conformational changes in the terminase of
      bacteriophage T7 (gp19). The recording of the cantilever bending during its
      functionalization shows the existence of a gp19 monolayer arrangement confirmed
      by atomic force microscopy of the immobilized proteins. The ATP hydrolysis of the
      gp19 terminase generates a stepped motion of the cantilever and points to a
      mechanical cooperative effect among gp19 oligomers. Furthermore, the effect of
      ATP can be counteracted by non-hydrolyzable nucleotide analogs.

PMID- 22156041
TI  - A cohort study of hyperuricemia in middle-aged South Korean men.
AB  - Few prospective studies have assessed the incidence and determinants of
      asymptomatic hyperuricemia in free-living populations. The authors' goals in this
      study were to estimate the incidence of hyperuricemia and quantify the dose
      response relations of specific risk factors with hyperuricemia in middle-aged
      South Korean male workers. The authors followed a cohort of 10,802 hyperuricemia
      free men aged 30-59 years, examining them annually or biennially at a university
      hospital in Seoul, South Korea, from 2002 to 2009. A parametric Cox model and a
      pooled logistic regression model were used to estimate adjusted hazard ratios for
      incident hyperuricemia (defined as serum uric acid level >=7.0 mg/dL) according
      to prespecified risk factors. During 51,210.6 person-years of follow-up, 2,496
      men developed hyperuricemia (incidence rate = 48.7 per 1,000 person-years, 95%
      confidence interval: 46.8, 50.7). The incidence of hyperuricema increased across
      baseline categories of age, body mass index, alcohol intake, blood pressure,
      metabolic syndrome, high-sensitivity C-reactive protein, triglycerides, gamma
      glutamyltransferase, and fatty liver, whereas fasting glucose, estimated
      glomerular filtration rate, and high density lipoprotein cholesterol levels were
      inversely associated with incident hyperuricemia. Development of hyperuricemia, a
      very common outcome among apparently healthy South Korean men, was predicted by a
      variety of cardiovascular and metabolic risk factors, suggesting that lifestyle
      modification may help reduce the incidence of hyperuricemia.

PMID- 22156042
TI  - Integrated device for combined optical neuromodulation and electrical recording
      for chronic in vivo applications.
AB  - Studying brain function and its local circuit dynamics requires neural interfaces
      that can record and stimulate the brain with high spatiotemporal resolution.
      Optogenetics, a technique that genetically targets specific neurons to express
      light-sensitive channel proteins, provides the capability to control central
      nervous system neuronal activity in mammals with millisecond time precision. This
      technique enables precise optical stimulation of neurons and simultaneous
      monitoring of neural response by electrophysiological means, both in the vicinity
      of and distant to the stimulation site. We previously demonstrated, in vitro, the
      dual capability (optical delivery and electrical recording) while testing a novel
      hybrid device (optrode-MEA), which incorporates a tapered coaxial optical
      electrode (optrode) and a 100 element microelectrode array (MEA). Here we report
      a fully chronic implant of a new version of this device in ChR2-expressing rats,
      and demonstrate its use in freely moving animals over periods up to 8 months. In
      its present configuration, we show the device delivering optical excitation to a
      single cortical site while mapping the neural response from the surrounding 30
      channels of the 6 * 6 element MEA, thereby enabling recording of optically
      modulated single-unit and local field potential activity across several
      millimeters of the neocortical landscape.

PMID- 22156043
TI  - The aporphine alkaloid boldine improves endothelial function in spontaneously
      hypertensive rats.
AB  - Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent
      antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of
      endothelial dysfunction in hypertension. In the present study, we investigated
      the effects of boldine on endothelial dysfunction in hypertension using
      spontaneously hypertensive rats (SHR), the most studied animal model of
      hypertension. SHR and their age-matched normotensive Wistar-Kyoto (WKY) rats were
      treated with boldine (20 mg/kg per day) or its vehicle, which served as control,
      for seven days. Control SHR displayed higher systolic blood pressure (SBP),
      reduced endothelium-dependent aortic relaxation to acetylcholine (ACh),
      marginally attenuated endothelium-independent aortic relaxation to sodium
      nitroprusside (SNP), increased aortic superoxide and peroxynitrite production,
      and enhanced p47(phox) protein expression as compared with control WKY rats.
      Boldine treatment significantly lowered SBP in SHR but not in WKY. Boldine
      treatment enhanced the maximal relaxation to ACh in SHR, but had no effect in
      WKY, whereas the sensitivity to ACh was increased in both SHR and WKY aortas.
      Boldine treatment enhanced sensitivity, but was without effect on maximal aortic
      relaxation responses, to SNP in both WKY and SHR aortas. In addition, boldine
      treatment lowered aortic superoxide and peroxynitrite production and
      downregulated p47(phox) protein expression in SHR aortas, but had no effect in
      the WKY control. These results show that boldine treatment exerts endothelial
      protective effects in hypertension, achieved, at least in part, through the
      inhibition of NADPH-mediated superoxide production.

PMID- 22156044
TI  - The tissue engineering of articular cartilage: cells, scaffolds and stimulating
      factors.
AB  - Damage or loss of articular cartilage as a consequence of congenital anomaly,
      degenerative joint disease or injury leads to progressive debilitation, which has
      a negative impact on the quality of life of affected individuals in all age
      groups. Classical surgical techniques for hyaline cartilage reparation are
      frequently insufficient and in many cases it is not possible to obtain the
      expected results. For this reason, researchers and surgeons are forced to find a
      method to induce complete cartilage repair. Recently, the advent of tissue
      engineering has provided alternative possibilities for the treatment of these
      patients by application of cell-based therapy (e.g. chondrocytes and adult stem
      cells) combined with synthetic substitutes of the extracellular matrix and
      bioactive factors to prepare functional replacement of hyaline cartilage. This
      communication is aimed at a brief review of the current status of cartilage
      tissue engineering and recent advances in the field.

PMID- 22156045
TI  - Acupuncture at ST36 prevents chronic stress-induced increases in neuropeptide Y
      in rat.
AB  - Chronic stress, as seen in post-traumatic stress disorder, can exacerbate
      existing diseases. Electroacupuncture (EA) has been proposed to treat chronic
      stress, although information on its efficacy or mechanism(s) of action is
      limited. While many factors contribute to the chronic stress response, the
      sympathetic peptide, neuropeptide Y (NPY), has been shown to be elevated in
      chronic stress and is hypothesized to contribute to the physiological stress
      response. Our objective was to determine if EA at acupuncture point stomach 36
      (ST(36)) is effective in mitigating cold stress-induced increase in NPY in rats.
      Both pretreatment and concomitant treatment with EA ST(36) effectively suppressed
      peripheral and central NPY after 14 d of cold stress (P < 0.05). The effect was
      specific, as NPY in Sham-EA rats was not different than observed in stress-only
      rats. Additionally, the effect of EA ST(36) was long-lasting, as NPY levels
      remained suppressed despite early cessation of EA ST(36), while exposure to cold
      stress was continued. In the paraventricular nucleus (PVN), it was notable that
      changes in NPY mirrored plasma NPY levels, and that the significant elevation in
      PVN Y1 receptor observed with stress was also prevented with EA ST(36). The
      findings indicate that EA ST(36) is effective in preventing one of the
      sympathetic pathways stimulated during chronic stress, and thus may be a useful
      adjunct therapy in stress-related disorders.

PMID- 22156046
TI  - Bispecific tandem single chain antibody simultaneously inhibits beta-secretase
      and promotes alpha-secretase processing of AbetaPP.
AB  - Misfolding and aggregation of amyloid-beta (Abeta) is an important early event in
      the pathogenesis of Alzheimer's disease. Abeta is produced by sequential
      proteolysis of the amyloid-beta protein precursor (AbetaPP) by beta- and gamma
      secretases. A third protease, alpha-secretase, cleaves AbetaPP in the middle of
      the Abeta sequence precluding formation of Abeta. The levels of Abeta generated
      from AbetaPP can therefore be controlled by tailoring activity of these proteases
      toward AbetaPP. We previously showed that beta-secretase proteolysis of AbetaPP
      could be selectively inhibited using the single chain antibody fragment (scFv)
      iBSEC1, which blocks the cleavage site on AbetaPP, and alpha-secretase
      proteolysis of AbetaPP could be selectively enhanced using a proteolytic scFv
      (Asec1A) engineered to have alpha-secretase-like activity. Here we show that
      DIA10D, a novel tandem bispecific scFv combining iBSEC1 with the ASec1A can
      control amyloidogenic processing of AbetaPP by simultaneously inhibiting beta
      secretase and increasing alpha-secretase processing of AbetaPP. When expressed in
      H4 (neuroglioma) cells overexpressing AbetaPP, DIA10D potently reduces levels of
      extracellular Abeta by around 50% while also increasing levels of neuroprotective
      sAbetaPPalpha. DIA10D activity has been designed to selectively target AbetaPP,
      so this modulation of AbetaPP processing should not affect endogenous activity of
      alpha-and beta-secretases towards other substrates.

PMID- 22156047
TI  - Methods for analysis of amyloid-beta aggregates.
AB  - Amyloid-beta protein (Abeta) accumulation is one of the major hallmarks of
      Alzheimer's disease and plays a crucial role in its pathogenesis. Abeta
      aggregates into fibrils, but rather than these end-products of the aggregation
      process, intermediate species, referred to as oligomers, have been identified as
      the most neurotoxic Abeta aggregates. To characterize the different Abeta species
      and to study the aggregation process, a wide range of techniques has been applied
      over the past years. These techniques aim to visualize the different Abeta
      species and study their structure, to separate them, and to quantify the
      aggregated Abeta forms by immunology-based methods. In this review, we provide an
      overview and discussion of the most important techniques used for these aims.
      Often a combination of techniques will be appropriate to obtain the most optimal
      information.

PMID- 22156048
TI  - Amyloid imaging with AV45 ((18)F-florbetapir) in a cognitively normal AbetaPP
      duplication carrier.
AB  - We report the case of a 62-year-old asymptomatic carrier of AbetaPP gene
      duplication. He was investigated by MRI and the amyloid ligand (18)F-AV45, and
      compared to Alzheimer's disease patients (n = 11) and healthy controls (n = 11).
      The neuropsychological examination was normal. Cortical thickness and AV45
      retention were comparable to Alzheimer's disease patients. AbetaPP duplication
      was diagnosed because cerebral amyloid angiopathy and Alzheimer's disease
      pathology were found on the neuropathological examination of his youngest
      brother, who died at 42 from intracerebral hemorrhage. This is the first
      description of a pre-symptomatic AbetaPP duplication carrier over 60, despite
      widespread cerebral amyloid angiopathy, "Alzheimer's like" atrophy, and amyloid
      deposition.

PMID- 22156049
TI  - Theory of mind in amnestic mild cognitive impairment: an FMRI study.
AB  - Theory of Mind (ToM) undergoes changes at the behavioral level in pathological
      aging (Alzheimer's disease (AD)) and at the neural level in physiological aging.
      The aim was to determine if there are changes in ToM in the behavioral and neural
      domains in old subjects with high risk of switching from successful to
      unsuccessful neurocognitive aging. Patients with amnestic mild cognitive
      impairment (aMCI) syndrome were studied, since aMCI was proposed to fill the gap
      between normal aging and dementia. Sixteen aMCI patients (mean age 71 years) and
      fifteen healthy controls (mean age 67 years) with no differences in age or
      education were subjected to increasingly complex ToM tasks and to fMRI scanning
      while performing the Reading the Mind in the Eyes test (RME), which attributes
      mental states by focusing on eye-gaze. aMCI subjects had worse performances in
      two second order false belief tasks, confirming the decay of ToM on the
      behavioral level. Despite a minor activation of some components (posterior end of
      the superior temporal sulcus and temporal pole) of the ToM neural circuit, no
      significant differences in the behavioral performances to the RME was found in
      aMCI compared to controls. Probably the preservation of the mirror neuron system
      (precentral gyrus-BA 6; Broca area - BA 44) and the stronger involvement of
      frontal areas (middle and medial frontal cortex and anterior cingulate cortex)
      supplemented the decay of part of the mentalizing neural circuit, preserving task
      performance.

PMID- 22156050
TI  - Multi-feature-based plaque characterization in ex vivo MRI trained by
      registration to 3D histology.
AB  - We present a new method for automated characterization of atherosclerotic plaque
      composition in ex vivo MRI. It uses MRI intensities as well as four other types
      of features: smoothed, gradient magnitude and Laplacian images at several scales,
      and the distances to the lumen and outer vessel wall. The ground truth for
      fibrous, necrotic and calcified tissue was provided by histology and MUCT in 12
      carotid plaque specimens. Semi-automatic registration of a 3D stack of
      histological slices and MUCT images to MRI allowed for 3D rotations and in-plane
      deformations of histology. By basing voxelwise classification on different
      combinations of features, we evaluated their relative importance. To establish
      whether training by 3D registration yields different results than training by 2D
      registration, we determined plaque composition using (1) a 2D slice-based
      registration approach for three manually selected MRI and histology slices per
      specimen, and (2) an approach that uses only the three corresponding MRI slices
      from the 3D-registered volumes. Voxelwise classification accuracy was best when
      all features were used (73.3 +/- 6.3%) and was significantly better than when
      only original intensities and distance features were used (Friedman, p < 0.05).
      Although 2D registration or selection of three slices from the 3D set slightly
      decreased accuracy, these differences were non-significant.

PMID- 22156051
TI  - Raman scattering study of delafossite magnetoelectric multiferroic compounds:
      CuFeO2 and CuCrO2.
AB  - Ultrasonic velocity measurements on the magnetoelectric multiferroic compound
      CuFeO(2) reveal that the antiferromagnetic transition observed at T(N1) = 14 K
      might be induced by an R3m --> pseudoproper ferroelastic transition. In that
      case, the group theory states that the order parameter associated with the
      structural transition must belong to a two-dimensional irreducible representation
      E(g) (x(2) - y(2), xy). Since this type of transition can be driven by a Raman
      E(g) mode, we performed Raman scattering measurements on CuFeO(2) between 5 and
      290 K. Considering that the isostructural multiferroic compound CuCrO(2) might
      show similar structural deformations at the antiferromagnetic transition T(N1) =
      24.3 K, Raman measurements have also been performed for comparison. At ambient
      temperature, the Raman modes in CuFeO(2) are observed at omega(E(g)) = 352 cm(-1)
      and omega(A(1g)) = 692 cm(-1), while these modes are detected at omega(E(g)) =
      457 cm(-1) and omega(A(1g)) = 709 cm(-1) in CuCrO(2). The analysis of the
      temperature dependence of the modes in both compounds shows that the frequencies
      of all modes increase with decreasing temperature. This typical behavior is
      attributed to anharmonic phonon-phonon interactions. These results clearly
      indicate that none of the Raman active modes observed in CuFeO(2) and CuCrO(2)
      drive the pseudoproper ferroelastic transitions observed at the Neel temperature
      T(N1). Finally, a broad band at about 550 cm(-1) observed in the magnetoelectric
      phase of CuCrO(2) below T(N2) could be associated with magnons.

PMID- 22156052
TI  - Empty nest syndrome in China.

PMID- 22156054
TI  - Wide-range hydrogen sensing with Nb-doped TiO2 nanotubes.
AB  - Anatase-type titania nanotubes doped with Nb element were fabricated through an
      anodization of Ti35Nb alloy substrate and further annealing at 450  degrees C.
      Hydrogen sensitivity of the Nb-doped TiO(2) nanotubes at room temperature was
      investigated through exposure of the nanotube samples to different hydrogen
      atmospheres. At room temperature, the Nb-doped nanotubes demonstrated a good
      sensitivity for wide-range detection of both dilute and high-concentration
      hydrogen atmospheres ranging from 50 ppm to 2% H(2). The Nb-doped nanotubes also
      presented remarkable reversibility and repeatability as well as a quick response
      to the hydrogen atmosphere. The Nb-doped titania nanotubes have great advantages
      as robust and wide-range hydrogen sensors operating at room temperature.

PMID- 22156056
TI  - Genetic structure and differentiation of the Italian catria horse.
AB  - Catria is 1 of the 22 native Italian horse breeds that now survive from a larger
      number. Thirty individuals, representative of the Catria horse, were analyzed for
      11 microsatellites and compared with data of 10 breeds reared in Italy. Three
      different approaches, genetic distances, correspondence analysis, and clustering
      methods, were considered to study genetic relationships among Catria and the
      other horse populations. Genetic differentiation among breeds was highly
      significant (P < 0.01) for all loci. Average F(ST) values indicate that around
      10% of the total genetic variation was explained by the between-breed differences
      and the 3 approaches utilized gave similar results. Italian native breeds are
      clearly separated from the other examined breeds. However, by the correspondence
      analysis, the Catria appears closer to Maremmano and Murgese. The results of
      Bayesian approaches give further information showing for Catria a common origin
      with Maremmano and Italian Heavy Draught. Genetic relationships among Catria and
      the other breeds are consistent with the breed's documented history. The data and
      information found here can be utilized in the organization of conservation
      programmes planned to reduce inbreeding and to minimize loss of genetic
      variability.

PMID- 22156057
TI  - Stringency of start codon selection modulates autoregulation of translation
      initiation factor eIF5.
AB  - An AUG in an optimal nucleotide context is the preferred translation initiation
      site in eukaryotic cells. Interactions among translation initiation factors,
      including eIF1 and eIF5, govern start codon selection. Experiments described here
      showed that high intracellular eIF5 levels reduced the stringency of start codon
      selection in human cells. In contrast, high intracellular eIF1 levels increased
      stringency. High levels of eIF5 induced translation of inhibitory upstream open
      reading frames (uORFs) in eIF5 mRNA that initiate with AUG codons in conserved
      poor contexts. This resulted in reduced translation from the downstream eIF5
      start codon, indicating that eIF5 autoregulates its own synthesis. As with eIF1,
      which is also autoregulated through translation initiation, features contributing
      to eIF5 autoregulation show deep evolutionary conservation. The results obtained
      provide the basis for a model in which auto- and cross-regulation of eIF5 and
      eIF1 translation establish a regulatory feedback loop that would stabilize the
      stringency of start codon selection.

PMID- 22156058
TI  - Characterization of DNA methyltransferase specificities using single-molecule,
      real-time DNA sequencing.
AB  - DNA methylation is the most common form of DNA modification in prokaryotic and
      eukaryotic genomes. We have applied the method of single-molecule, real-time
      (SMRT(r)) DNA sequencing that is capable of direct detection of modified bases at
      single-nucleotide resolution to characterize the specificity of several bacterial
      DNA methyltransferases (MTases). In addition to previously described SMRT
      sequencing of N6-methyladenine and 5-methylcytosine, we show that N4
      methylcytosine also has a specific kinetic signature and is therefore
      identifiable using this approach. We demonstrate for all three prokaryotic
      methylation types that SMRT sequencing confirms the identity and position of the
      methylated base in cases where the MTase specificity was previously established
      by other methods. We then applied the method to determine the sequence context
      and methylated base identity for three MTases with unknown specificities. In
      addition, we also find evidence of unanticipated MTase promiscuity with some
      enzymes apparently also modifying sequences that are related, but not identical,
      to the cognate site.

PMID- 22156059
TI  - POLYPHEMUS: R package for comparative analysis of RNA polymerase II ChIP-seq
      profiles by non-linear normalization.
AB  - Chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq)
      is increasingly used to map protein-chromatin interactions at global scale. The
      comparison of ChIP-seq profiles for RNA polymerase II (PolII) established in
      different biological contexts, such as specific developmental stages or specific
      time-points during cell differentiation, provides not only information about the
      presence/accumulation of PolII at transcription start sites (TSSs) but also about
      functional features of transcription, including PolII stalling, pausing and
      transcript elongation. However, annotation and normalization tools for
      comparative studies of multiple samples are currently missing. Here, we describe
      the R-package POLYPHEMUS, which integrates TSS annotation with PolII enrichment
      over TSSs and coding regions, and normalizes signal intensity profiles. Thereby
      POLYPHEMUS facilitates to extract information about global PolII action to reveal
      changes in the functional state of genes. We validated POLYPHEMUS using a kinetic
      study on retinoic acid-induced differentiation and a publicly available data set
      from a comparative PolII ChIP-seq profiling in Caenorhabditis elegans. We
      demonstrate that POLYPHEMUS corrects the data sets by normalizing for technical
      variation between samples and reveal the potential of the algorithm in comparing
      multiple data sets to infer features of transcription regulation from dynamic
      PolII binding profiles.

PMID- 22156061
TI  - Ultra-nanocrystalline diamond electrodes: optimization towards neural stimulation
      applications.
AB  - Diamond is well known to possess many favourable qualities for implantation into
      living tissue including biocompatibility, biostability, and for some applications
      hardness. However, conducting diamond has not, to date, been exploited in neural
      stimulation electrodes due to very low electrochemical double layer capacitance
      values that have been previously reported. Here we present electrochemical
      characterization of ultra-nanocrystalline diamond electrodes grown in the
      presence of nitrogen (N-UNCD) that exhibit charge injection capacity values as
      high as 163 uC cm(-2) indicating that N-UNCD is a viable material for
      microelectrode fabrication. Furthermore, we show that the maximum charge
      injection of N-UNCD can be increased by tailoring growth conditions and by
      subsequent electrochemical activation. For applications requiring yet higher
      charge injection, we show that N-UNCD electrodes can be readily metalized with
      platinum or iridium, further increasing charge injection capacity. Using such
      materials an implantable neural stimulation device fabricated from a single piece
      of bio-permanent material becomes feasible. This has significant advantages in
      terms of the physical stability and hermeticity of a long-term bionic implant.

PMID- 22156060
TI  - Regulation of polysome assembly on the endoplasmic reticulum by a coiled-coil
      protein, p180.
AB  - A coiled-coil microtubule-bundling protein, p180, was originally identified as
      one of the ribosome receptor candidates on the rough endoplasmic reticulum (ER)
      and is highly expressed in secretory tissues. Recently, we reported that p180
      plays crucial roles in upregulating collagen biosynthesis, mainly by facilitating
      ribosome association on the ER. Here, we provide evidence that p180 is required
      to form translationally active polysome/translocon complexes on the ER. Assembly
      of highly-developed polysomes on the ER was severely perturbed upon loss of p180.
      p180 associates with polysome/translocon complexes through multiple contact
      sites: it was coimmunoprecipitated with the translocon complex independently of
      ribosomes, while it can also bind to ribosomal large subunit specifically. The
      responsible domain of p180 for membrane polysome assembly was identified in the C
      terminal coiled-coil region. The degree of ribosome occupation of collagen and
      fibronectin mRNAs was regulated in response to increased traffic demands. This
      effect appears to be exerted in a manner specific for a specified set of mRNAs.
      Collectively, our data suggest that p180 is required to form translationally
      active polysome/translocon complexes on the ER membrane, and plays a pivotal role
      in highly efficient biosynthesis on the ER membrane through facilitating polysome
      formation in professional secretory cells.

PMID- 22156062
TI  - 4D micro-CT using fast prospective gating.
AB  - Micro-CT is currently used in preclinical studies to provide anatomical
      information. But, there is also significant interest in using this technology to
      obtain functional information. We report here a new sampling strategy for 4D
      micro-CT for functional cardiac and pulmonary imaging. Rapid scanning of free
      breathing mice is achieved with fast prospective gating (FPG) implemented on a
      field programmable gate array. The method entails on-the-fly computation of
      delays from the R peaks of the ECG signals or the peaks of the respiratory
      signals for the triggering pulses. Projection images are acquired for all cardiac
      or respiratory phases at each angle before rotating to the next angle. FPG can
      deliver the faster scan time of retrospective gating (RG) with the regular
      angular distribution of conventional prospective gating for cardiac or
      respiratory gating. Simultaneous cardio-respiratory gating is also possible with
      FPG in a hybrid retrospective/prospective approach. We have performed phantom
      experiments to validate the new sampling protocol and compared the results from
      FPG and RG in cardiac imaging of a mouse. Additionally, we have evaluated the
      utility of incorporating respiratory information in 4D cardiac micro-CT studies
      with FPG. A dual-source micro-CT system was used for image acquisition with
      pulsed x-ray exposures (80 kVp, 100 mA, 10 ms). The cardiac micro-CT protocol
      involves the use of a liposomal blood pool contrast agent containing 123 mg I ml(
      1) delivered via a tail vein catheter in a dose of 0.01 ml g(-1) body weight. The
      phantom experiment demonstrates that FPG can distinguish the successive phases of
      phantom motion with minimal motion blur, and the animal study demonstrates that
      respiratory FPG can distinguish inspiration and expiration. 4D cardiac micro-CT
      imaging with FPG provides image quality superior to RG at an isotropic voxel size
      of 88 MUm and 10 ms temporal resolution. The acquisition time for either sampling
      approach is less than 5 min. The radiation dose associated with the proposed
      method is in the range of a typical micro-CT dose (256 mGy for the cardiac
      study). Ignoring respiration does not significantly affect anatomic information
      in cardiac studies. FPG can deliver short scan times with low-dose 4D micro-CT
      imaging without sacrificing image quality. FPG can be applied in high-throughput
      longitudinal studies in a wide range of applications, including drug safety and
      cardiopulmonary phenotyping.

PMID- 22156067
TI  - Structural and magnetic properties of CrSb compounds: NiAs structure.
AB  - The structural and magnetic properties of CrSb compounds with NiAs structure have
      been studied by means of the Korringa-Kohn-Rostoker (KKR) band structure method.
      An analysis of the structural and magnetic stability has been performed on the
      basis of total energy calculations for various magnetic states. The magnetic
      properties at finite temperature have been investigated by means of Monte Carlo
      simulations on the basis of a classical Heisenberg Hamiltonian and the exchange
      coupling parameters calculated from first principles. This approach allowed us to
      determine the critical temperature in good agreement with experiment.

PMID- 22156068
TI  - Ordered porous diamond films fabricated by colloidal crystal templating.
AB  - We have developed a colloidal crystal templating method for preparation of
      diamond films with 2D and 3D ordered porous structures. The technological process
      involved breaks down into (a) impregnation into the pores of silica colloidal
      crystal (opal) films of detonation nanodiamond (DND) particles from their
      hydrosol; (b) microwave plasma-enhanced chemical vapor deposition (MWPECVD)
      regrowth with diamond of pores with high DND filling; (c) Ar(+) ion dry etching
      of fragments of shells of coalesced diamond crystallites which form in the course
      of MWPECVD on the surface of the SiO(2) beads making up the outer surface of a
      film and (d) wet etching of the SiO(2) template in aqueous HF solution. The final
      samples are either connected to the substrate or free-standing films of various
      thicknesses having 2D or 3D ordered porous structures. The morphology of the
      diamond films fabricated by this method replicates the pore network of the opal
      template. Raman measurements confirm the diamond structure of the synthesized
      ordered porous material.

PMID- 22156069
TI  - Context-aware brain-computer interfaces: exploring the information space of user,
      technical system and environment.
AB  - Brain-computer interface (BCI) systems are usually applied in highly controlled
      environments such as research laboratories or clinical setups. However, many BCI
      based applications are implemented in more complex environments. For example,
      patients might want to use a BCI system at home, and users without disabilities
      could benefit from BCI systems in special working environments. In these
      contexts, it might be more difficult to reliably infer information about brain
      activity, because many intervening factors add up and disturb the BCI feature
      space. One solution for this problem would be adding context awareness to the
      system. We propose to augment the available information space with additional
      channels carrying information about the user state, the environment and the
      technical system. In particular, passive BCI systems seem to be capable of adding
      highly relevant context information-otherwise covert aspects of user state. In
      this paper, we present a theoretical framework based on general human-machine
      system research for adding context awareness to a BCI system. Building on that,
      we present results from a study on a passive BCI, which allows access to the
      covert aspect of user state related to the perceived loss of control. This study
      is a proof of concept and demonstrates that context awareness could beneficially
      be implemented in and combined with a BCI system or a general human-machine
      system. The EEG data from this experiment are available for public download at
      www.phypa.org.

PMID- 22156070
TI  - Exploring the role of gender and risk perceptions in people's decisions to
      register as a bone marrow donor.
AB  - Increasing the number of bone marrow (BM) donors is important to ensure
      sufficient diversity on BM registries to meet the needs of patients. This study
      used an experimental approach to test the hypothesis that providing information
      about the risks of BM donation to allay unsubstantiated fears would reduce male
      and female participants' perceptions of risk for donation and joining the
      Australian Bone Marrow Donor Registry (ABMDR). Males' and females' intentions to
      register on the ABMDR and their attitudes, norms and perceived behavioural
      control (efficacy) in relation to registering were also explored. Participants
      were allocated randomly to either a risk (exposed to risk information about BM
      donation) or no-risk (not exposed to risk information) condition. In partial
      support of hypotheses, exposure to risk information did reduce perceived risk for
      registering on the ABMDR for males only. Participants in the risk condition also
      demonstrated lower scores on attitude (males only) and intention compared with
      participants in the no-risk condition. These findings highlight the complex role
      of risk perceptions and gender differences in understanding people's decisions to
      join a BM registry.

PMID- 22156072
TI  - Antidepressants: Their efficacy and place in therapy.
AB  - This paper reviews and relates to the wider published literature a series of
      studies directed to the broad question of which antidepressant treatment is
      required for which kind of depressed patient. Adequate methodology requires
      comparisons with placebo and other active drugs, rather than analysis of single
      treatment groups, so that the magnitude of therapeutic benefit due to specific
      drug effects can be measured. Reasonably firm conclusions are now possible.
      Electroconvulsive therapy (ECT) is most effective in severely depressed patients,
      particularly those with delusions or retardation, and is superior to
      antidepressant drugs in such patients. Monoamine oxidase (MAO) inhibitors show
      some selectivity towards patients with anxiety or reversed functional shift
      symptoms, but this selectivity appears quite limited, and tricyclic
      antidepressants also benefit such patients. The possibility of other factors, not
      well reflected in clinical features, which determine consistency of response
      requires further investigation. Recent evidence has led to re-evaluation of the
      earlier view that tricyclic antidepressants were specifically indicated in
      endogenous depressions. They appear to be broad-spectrum antidepressants, with
      efficacy extending more widely into neurotic disorders, mixed anxiety
      depressions, anxiety disorders, and into the relatively mild non-endogenous
      depressions of general practice.

PMID- 22156071
TI  - Smoking frequency among current college student smokers: distinguishing
      characteristics and factors related to readiness to quit smoking.
AB  - Given the increased prevalence of non-daily smoking and changes in smoking
      patterns, particularly among young adults, we examined correlates of smoking
      level, specifically motives for smoking, and readiness to quit smoking among 2682
      college undergraduates who completed an online survey. Overall, 64.7% (n = 1736)
      were non-smokers, 11.6% (n = 312) smoked 1-5 days, 10.5% (n = 281) smoked 6-29
      days and 13.2% (n = 353) were daily smokers. Ordinal regression analyses modeling
      smoking level indicated that correlates of higher smoking level included having
      more friends who smoke (beta = 0.63, 95% CI 0.57-0.69) and more frequent other
      tobacco use (beta = 0.04, 95% CI 0.02-0.05), drinking (beta = 0.04, 95% CI 0.02
      0.07) and binge drinking (beta = 0.09, 95% CI 0.06-0.13). Bivariate analyses
      indicated that daily smokers (versus the subgroups of non-daily smokers) were
      less likely to smoke for social reasons but more likely to smoke for self
      confidence, boredom, and affect regulation. Controlling for sociodemographics,
      correlates of readiness to quit among current smokers included fewer friends who
      smoke (P = 0.002), less frequent binge drinking (P = 0.03), being a social smoker
      (P < 0.001), smoking less for self-confidence (P = 0.04), smoking more for
      boredom (P = 0.03) and less frequent smoking (P = 0.001). Specific motives for
      smoking and potential barriers to cessation particularly may be relevant to
      different groups of college student smokers.

PMID- 22156073
TI  - Clonidine challenge testing of alpha-2-adrenoceptor function in man: the effects
      of mental illness and psychotropic medication.
AB  - The clonidine challenge test is a means of assessing alpha-2-adrenoceptor sen
      sitivity in man. We review studies which have used this test to investigate
      central alpha-2- adrenoceptor changes in psychiatric illness, and to determine
      receptor changes after adminis tration and withdrawal of psychotropic treatments.
      Patients with severe depression show evidence of reduced alpha-2-adrenoceptor
      sensitivity, especially a reduced growth hormone response to clonidine. This may
      delineate a subgroup of patients with severe depressive illness from those with
      milder depression, and may even provide a trait marker for some depressed
      patients. Patients with panic disorder show evidence of subsensitivity to some
      and supersensitivity to other clonidine-induced responses. Other disorders,
      although less well investigated, may have abnormal test responses which may
      provide additional information about their cause and treatment. Changes in
      response after drug treatment have provided important information on the mode of
      action of antidepressants, and have suggested that noradrenergic function is
      altered by a variety of different antidepressants.

PMID- 22156074
TI  - Objective and subjective effects of remoxipride, alone and in combination with
      ethanol or diazepam, on performance in healthy subjects.
AB  - Effects on human performance of remoxipride (RX), an antipsychotic drug of
      substituted benzamide structure, were studied in a randomized double-blind
      crossover trial where 12 young healthy volunteers took at 1 week intervals single
      oral doses of placebo or remoxipiride 100 mg both alone and in combination with
      15 mg diazepam (DZ) or 0.8 g/kg ethanol (EtOH). Objective (digit symbols,
      tracking, choice reaction, flicker fusion, Maddox wing, body balance, memory) and
      subjective (visual analogue scales, questionnaire) tests were administered at
      baseline and 1.5, 3, 4.5 and 6 h post-treatment.

PMID- 22156075
TI  - Effects of an endogenous anxiolytic adrenal steroid, alpha-THDOC, on non-opioid
      defeat analgesia in male mice: interaction with Ro15-1788.
AB  - The effects of the putative anxiolytic adrenal steroid, 3alpha, 5alpha-tetrahydro
      deoxycorticosterone (alpha-THDOC), on non-opioid defeat analgesia in male mice
      were examined. Although devoid of intrinsic activity on the tail-flick assay, 5
      mg/kg alpha-THDOC was found to significantly attenuate the analgesic consequences
      of defeat experience; lower (2.5 mg/kg) and higher (10-20 mg/kg) doses were
      ineffective. The beta-isomer of THDOC also significantly reduced defeat
      analgesia, but only at the highest dose tested (20 mg/kg). Control experiments
      demonstrated that 5 per cent ethanol, which was employed as a vehicle for the
      steroids, was without effect per se on basal nociception and, over the limited
      dose range of 5-10 per cent, did not alter defeat analgesia. Finally, the
      benzodiazepine receptor antagonist, Ro15-1788 (5 mg/kg) failed to influence the
      inhibitory effects of either THDOC isomer. Results are discussed in relation to
      the potential modulation of this form of adaptive pain inhibition by adrenal
      steroids which influence the GABA receptor-coupled chloride ionophore.

PMID- 22156076
TI  - Symposium 2 animal models of depression and the detection of antidepressants
      chairman: p. S. J. Spencer (u.k.).

PMID- 22156078
TI  - Symposium 5 resistant depression and atypical depression: possible aetiologies
      and treatments chairman: R. Daly (ireland).

PMID- 22156077
TI  - Symposium 3 biochemical markers of depression and response to treatment chairman:
      a. Coppen (u.k.).

PMID- 22156079
TI  - Symposium 6 second generations antidepressants and antidepressants in development
      chairman: m. Sandler (u.k.).

PMID- 22156080
TI  - Symposium 7 adverse effects of antidepressants chairman: s. Montgomery (u.k.).

PMID- 22156081
TI  - Symposium 8 antidepressants in general practice chairman: m. Webb (ireland).

PMID- 22156083
TI  - Poster session - B.

PMID- 22156082
TI  - Poster session -- a.

PMID- 22156084
TI  - Psychiatric drug-induced Chronic Brain Impairment (CBI): implications for long
      term treatment with psychiatric medication.
AB  - Understanding the hazards associated with long-term exposure to psychiatric drugs
      is very important but rarely emphasized in the scientific literature and clinical
      practice. Drawing on the scientific literature and clinical experience, the
      author describes the syndrome of Chronic Brain Impairment (CBI) which can be
      caused by any trauma to the brain including Traumatic Brain Injury (TBI),
      electroconvulsive therapy (ECT), and long-term exposure to psychiatric
      medications. Knowledge of the syndrome should enable clinicians to more easily
      identify long-term adverse effects caused by psychiatric drugs while enabling
      researchers to approach the problem with a more comprehensive understanding of
      the common elements of brain injury as they are manifested after long-term
      exposure to psychiatric medications. Treatment options are also discussed.

PMID- 22156085
TI  - Oseltamivir and early deterioration leading to death: a proportional mortality
      study for 2009A/H1N1 influenza.
AB  - OBJECTIVE: To examine the epidemiological association between sudden
      deterioration leading to death and Tamiflu use. DESIGN: Proportional mortality
      study. SETTING: Japan. PARTICIPANTS: 162 deaths without deterioration before the
      first consultation among all 198 deaths of mostly confirmed 2009A/H1N1 influenza.
      POPULATION AT RISK: Age-specific population of influenza patients prescribed
      Tamiflu and Relenza. MAIN OUTCOME MEASURE: Age-stratified pooled odds ratio (OR)
      for early (within 12 hours) deterioration and overall death of Tamiflu prescribed
      to Relenza prescribed patients. RESULTS: Of 119 deaths after Tamiflu was
      prescribed, 38 deteriorated within 12 hours (28 within 6 hours), while of 15
      deaths after Relenza, none deteriorated within 12 hours. Pooled OR for early
      deterioration and overall death were 5.88 (95% CI: 1.30 to 26.6, p = 0.014) and
      1.91 (p = 0.031) respectively. Baseline characteristics including risk factors
      did not contribute to early deterioration after Tamiflu use. CONCLUSIONS: These
      data suggest Tamiflu use could induce sudden deterioration leading to death
      especially within 12 hours of prescription. These findings are consistent with
      sudden deaths observed in a series of animal toxicity studies, several reported
      case series and the results of prospective cohort studies. From "the
      precautionary principle" the potential harm of Tamiflu should be taken into
      account and further detailed studies should be conducted.

PMID- 22156086
TI  - Pharmacovigilance amongst doctors in private hospitals in Lagos West Senatorial
      District, Nigeria.
AB  - Appropriate practice of pharmacovigilance in Nigeria will require total
      involvement of the private medical practitioners considering their number and
      closeness to the community. Thus, the understanding and attitude of Doctors
      practicing in the private sectors, towards Pharmacovigilance, was investigated. A
      consecutive sampling was used to distribute two hundred and seventy
      questionnaires to consenting doctors in the private hospitals of the Lagos West
      Senatorial District. The response rate was 93% and the results showed that
      majority of the respondents, 208 (82.9%), have heard about pharmacovigilance and
      a large percentage (79.3%) defined pharmacovigilance correctly. However, most of
      the respondents, 141 (56.2%), did not know how to report ADRs and where to obtain
      the ADR forms (71.7%). Only 14 (5.6%) of the respondents reported ADRs in the
      last one month. However, the majority of the respondents (89.6%) were willing to
      practice pharmacovigilance if they are trained. There were significant
      associations (p < 0.05) between previous areas of practice of the respondents;
      the respondents' academic qualifications; years of experience and reporting of
      ADRs. The NPC has already been organizing series' of trainings for doctors on
      pharmacovigilance, however, more periodic trainings should be organized for
      doctors especially those practicing in private hospitals. The curriculum of
      medical schools should be reviewed for its pharmacovigilance content.

PMID- 22156087
TI  - Knowledge, attitude and practices associated with adverse drug reaction reporting
      amongst doctors in a teaching hospital.
AB  - AIM: This study was aimed at investigating the knowledge, attitude and practices
      associated with adverse drug reaction (ADR) reporting among doctors in a teaching
      hospital. METHODS: A total of 100 doctors working in a teaching hospital were
      evaluated with a questionnaire for their knowledge, attitude and practices
      related to ADR reporting and pharmacovigilance programmes. RESULTS: Nearly two
      third (66%) of the doctors knew the definition of ADR. Only one third (38%, 40%)
      could correctly define pharmacovigilance and adverse drug event (ADE)
      respectively. Although 100% of the doctors felt the need for a National
      Pharmacovigilance Programme (NPP) only approximately three fourth (73%) were
      aware of the existing programme in India and nearly half of the them (47%)
      actually knew the current status of the NPP at their institute. Surprisingly only
      one tenth of the doctors (10%) knew what should be reported. The majority (74.4%)
      felt that reactions to new drug should be reported and also those reactions that
      are serious and unusual. Only one third (30%) knew whom to report to and less
      than half (30%) had actually ever reported an ADR. CONCLUSION: The knowledge of
      ADRs and how to report them is inadequate among doctors. More awareness should be
      created regarding the purpose and usefulness of ADR reporting through Continuous
      Medical Education, training and integration of ADR reporting into the clinical
      activities of the doctors.

PMID- 22156088
TI  - The danger of imperfect regulation: OxyContin use in the United States and
      Canada.
AB  - Drug companies aggressively market their products to increase sales and economic
      rewards. Different countries have different regulatory regimes for controlling
      promotion. In the United States control rests directly with the Food and Drug
      Administration whereas Canada relies on a mixture of voluntary self-regulation
      and an autonomous agency. Each method has significant weaknesses. We examine
      these weaknesses by analyzing the promotion of OxyContin (the time release
      version of the opioid oxycodone) by Purdue in Canada and the United States. We
      then look at the association between promotion and the misuse and abuse of
      OxyContin in both countries. Finally, we advance specific recommendations for
      regulating promotion for drugs that may have a high abuse potential.

PMID- 22156089
TI  - Body Mass Index adjustment for sitting height for better assessment of obesity
      risks in Maltese women.
AB  - OBJECTIVE: This study is aimed to assess the influence of body shape on Body Mass
      Index (BMI) estimations by determining the Sitting Height to Standing height
      ratio. METHODS: The study population included 291 non-pregnant premenopausal
      Maltese women aged 20-54 years. These women were assessed using the following
      anthropometric measurements: Body weight (Kg), standing height (cm) and sitting
      height (cm). The Sitting-to-Standing Height (SH/S) ratio, the observed BMI (oBMI)
      based on the standing height, and the SH/S ratio-corrected BMI (cBMI) were
      calculated. The SPSS package version 18.0 was used for statistical calculations.
      RESULTS: The average SH/S ratio of the Maltese premenopausal women is 0.44. The
      mean oBMI is 25.06, while the mean cBMI is 34.49 (P value < 0.001). Applying the
      linear regression prediction model with either oBMI or cBMI as dependent
      variables and the SH/S ratio as independent variable proved that the sitting
      height is a significant predictor of both oBMI and cBMI (P value < 0.00001).
      CONCLUSIONS: The results suggest that the cohort of this study tend to have long
      legs relative to torso-length (low SH/S ratio). Thus, the oBMI will underestimate
      the actual BMI value. The correction of BMI for the sitting height in Maltese
      population will more correctly identify individuals at greater risk for chronic
      diseases.

PMID- 22156090
TI  - Factors influencing uptake of influenza vaccine amongst healthcare workers in a
      regional center after the A(H1N1) 2009 pandemic: lessons for improving
      vaccination rates.
AB  - BACKGROUND: Vaccination of health-care workers (HCWs) against seasonal influenza
      has been consistently recommended worldwide in order to prevent nosocomial
      transmission and ensure delivery of health-care services during outbreaks.
      Overall, immunization rates were low across all nation, including among HCWs.
      Little is known about the acceptability and compliance with seasonal influenza
      vaccine among HCWs after the A(H1N1) 2009 pandemic. PARTICIPANTS AND SETTING:
      Between 1st and 31 January 2011, we conducted a questionnaire-based survey at the
      Ibn Sina regional center (Rabat, Morocco). Seven hundred twenty one HCWs have
      answered about their influenza immunization during the 2010/2011 season, as well
      as the reasons for accepting or declining this vaccine. Finally, we compare our
      results with previous moroccan survey. RESULTS: A total of 122 HCWs (17%)
      reported having received the 2010/2011 seasonal vaccine; "self-protection" and
      "protection of the patient" were the most frequently adduced reasons for
      acceptance of the influenza vaccination, whereas media controversy during the
      pandemic was the main argument for refusal. DISCUSSION: The post pandemic
      seasonal influenza vaccination coverage among the HCWs in our institution was
      very low. The role of media, specific attitudinal barriers and misconceptions
      about immunization in a global pandemic scenario is clear. The nearly constant
      media coverage of the A (H1N1) 2009 pandemic, reported with varying degrees of
      accuracy, and sometimes portraying dramatic scenarios caused some to question
      whether unnecessary alarm and public panic resulted. We suggest that
      international or national health authorities have a clear speech over looked
      media and to own these institutions, which will air fair and real time
      information about the disease.

PMID- 22156091
TI  - WHO Director-General names Sir Liam Donaldson envoy for patient safety.

PMID- 22156094
TI  - HMM-based lexicon-driven and lexicon-free word recognition for online handwritten
      Indic scripts.
AB  - Research for recognizing online handwritten words in Indic scripts is at its
      early stages when compared to Latin and Oriental scripts. In this paper, we
      address this problem specifically for two major Indic scripts--Devanagari and
      Tamil. In contrast to previous approaches, the techniques we propose are largely
      data driven and script independent. We propose two different techniques for word
      recognition based on Hidden Markov Models (HMM): lexicon driven and lexicon free.
      The lexicon-driven technique models each word in the lexicon as a sequence of
      symbol HMMs according to a standard symbol writing order derived from the
      phonetic representation. The lexicon-free technique uses a novel Bag-of-Symbols
      representation of the handwritten word that is independent of symbol order and
      allows rapid pruning of the lexicon. On handwritten Devanagari word samples
      featuring both standard and nonstandard symbol writing orders, a combination of
      lexicon-driven and lexicon-free recognizers significantly outperforms either of
      them used in isolation. In contrast, most Tamil word samples feature the standard
      symbol order, and the lexicon-driven recognizer outperforms the lexicon free one
      as well as their combination. The best recognition accuracies obtained for 20,000
      word lexicons are 87.13 percent for Devanagari when the two recognizers are
      combined, and 91.8 percent for Tamil using the lexicon-driven technique.

PMID- 22156095
TI  - Motion detail preserving optical flow estimation.
AB  - A common problem of optical flow estimation in the multiscale variational
      framework is that fine motion structures cannot always be correctly estimated,
      especially for regions with significant and abrupt displacement variation. A
      novel extended coarse-to-fine (EC2F) refinement framework is introduced in this
      paper to address this issue, which reduces the reliance of flow estimates on
      their initial values propagated from the coarse level and enables recovering many
      motion details in each scale. The contribution of this paper also includes
      adaptation of the objective function to handle outliers and development of a new
      optimization procedure. The effectiveness of our algorithm is demonstrated by
      Middlebury optical flow benchmarkmarking and by experiments on challenging
      examples that involve large-displacement motion.

PMID- 22156096
TI  - UBoost: boosting with the Universum.
AB  - It has been shown that the Universum data, which do not belong to either class of
      the classification problem of interest, may contain useful prior domain knowledge
      for training a classifier [1], [2]. In this work, we design a novel boosting
      algorithm that takes advantage of the available Universum data, hence the name
      UBoost. UBoost is a boosting implementation of Vapnik's alternative capacity
      concept to the large margin approach. In addition to the standard regularization
      term, UBoost also controls the learned model's capacity by maximizing the number
      of observed contradictions. Our experiments demonstrate that UBoost can deliver
      improved classification accuracy over standard boosting algorithms that use
      labeled data alone.

PMID- 22156097
TI  - Free Energy Score Spaces: Using Generative Information in Discriminative
      Classifiers.
AB  - A score function induced by a generative model of the data can provide a feature
      vector of a fixed dimension for each data sample. Data samples themselves may be
      of differing lengths (e.g., speech segments or other sequential data), but as a
      score function is based on the properties of the data generation process, it
      produces a fixed-length vector in a highly informative space, typically referred
      to as "score space." Discriminative classifiers have been shown to achieve higher
      performances in appropriately chosen score spaces with respect to what is
      achievable by either the corresponding generative likelihood-based classifiers or
      the discriminative classifiers using standard feature extractors. In this paper,
      we present a novel score space that exploits the free energy associated with a
      generative model. The resulting free energy score space (FESS) takes into account
      the latent structure of the data at various levels and can be shown to lead to
      classification performance that at least matches the performance of the free
      energy classifier based on the same generative model and the same factorization
      of the posterior. We also show that in several typical computer vision and
      computational biology applications the classifiers optimized in FESS outperform
      the corresponding pure generative approaches, as well as a number of previous
      approaches combining discriminating and generative models. 

PMID- 22156098
TI  - Tracking-Learning-Detection.
AB  - This paper investigates long-term tracking of unknown objects in a video stream.
      The object is defined by its location and extent in a single frame. In every
      frame that follows, the task is to determine the object's location and extent or
      indicate that the object is not present. We propose a novel tracking framework
      (TLD) that explicitly decomposes the long-term tracking task into tracking,
      learning, and detection. The tracker follows the object from frame to frame. The
      detector localizes all appearances that have been observed so far and corrects
      the tracker if necessary. The learning estimates the detector's errors and
      updates it to avoid these errors in the future. We study how to identify the
      detector's errors and learn from them. We develop a novel learning method (P-N
      learning) which estimates the errors by a pair of "experts": (1) P-expert
      estimates missed detections, and (2) N-expert estimates false alarms. The
      learning process is modeled as a discrete dynamical system and the conditions
      under which the learning guarantees improvement are found. We describe our real
      time implementation of the TLD framework and the P-N learning. We carry out an
      extensive quantitative evaluation which shows a significant improvement over
      state-of-the-art approaches. 

PMID- 22156099
TI  - Density-based multifeature background subtraction with support vector machine.
AB  - Background modeling and subtraction is a natural technique for object detection
      in videos captured by a static camera, and also a critical preprocessing step in
      various high-level computer vision applications. However, there have not been
      many studies concerning useful features and binary segmentation algorithms for
      this problem. We propose a pixelwise background modeling and subtraction
      technique using multiple features, where generative and discriminative techniques
      are combined for classification. In our algorithm, color, gradient, and Haar-like
      features are integrated to handle spatio-temporal variations for each pixel. A
      pixelwise generative background model is obtained for each feature efficiently
      and effectively by Kernel Density Approximation (KDA). Background subtraction is
      performed in a discriminative manner using a Support Vector Machine (SVM) over
      background likelihood vectors for a set of features. The proposed algorithm is
      robust to shadow, illumination changes, spatial variations of background. We
      compare the performance of the algorithm with other density-based methods using
      several different feature combinations and modeling techniques, both
      quantitatively and qualitatively.

PMID- 22156100
TI  - IntentSearch: Capturing User Intention for One-Click Internet Image Search.
AB  - Web-scale image search engines (e.g., Google image search, Bing image search)
      mostly rely on surrounding text features. It is difficult for them to interpret
      users' search intention only by query keywords and this leads to ambiguous and
      noisy search results which are far from satisfactory. It is important to use
      visual information in order to solve the ambiguity in text-based image retrieval.
      In this paper, we propose a novel Internet image search approach. It only
      requires the user to click on one query image with minimum effort and images from
      a pool retrieved by text-based search are reranked based on both visual and
      textual content. Our key contribution is to capture the users' search intention
      from this one-click query image in four steps. 1) The query image is categorized
      into one of the predefined adaptive weight categories which reflect users' search
      intention at a coarse level. Inside each category, a specific weight schema is
      used to combine visual features adaptive to this kind of image to better rerank
      the text-based search result. 2) Based on the visual content of the query image
      selected by the user and through image clustering, query keywords are expanded to
      capture user intention. 3) Expanded keywords are used to enlarge the image pool
      to contain more relevant images. 4) Expanded keywords are also used to expand the
      query image to multiple positive visual examples from which new query specific
      visual and textual similarity metrics are learned to further improve content
      based image reranking. All these steps are automatic, without extra effort from
      the user. This is critically important for any commercial web-based image search
      engine, where the user interface has to be extremely simple. Besides this key
      contribution, a set of visual features which are both effective and efficient in
      Internet image search are designed. Experimental evaluation shows that our
      approach significantly improves the precision of top-ranked images and also the
      user experience. 

PMID- 22156101
TI  - Aggregating local image descriptors into compact codes.
AB  - This paper addresses the problem of large-scale image search. Three constraints
      have to be taken into account: search accuracy, efficiency, and memory usage. We
      first present and evaluate different ways of aggregating local image descriptors
      into a vector and show that the Fisher kernel achieves better performance than
      the reference bag-of-visual words approach for any given vector dimension. We
      then jointly optimize dimensionality reduction and indexing in order to obtain a
      precise vector comparison as well as a compact representation. The evaluation
      shows that the image representation can be reduced to a few dozen bytes while
      preserving high accuracy. Searching a 100 million image data set takes about 250
      ms on one processor core.

PMID- 22156102
TI  - Bilinear modeling via augmented Lagrange multipliers (BALM).
AB  - This paper presents a unified approach to solve different bilinear factorization
      problems in computer vision in the presence of missing data in the measurements.
      The problem is formulated as a constrained optimization where one of the factors
      must lie on a specific manifold. To achieve this, we introduce an equivalent
      reformulation of the bilinear factorization problem that decouples the core
      bilinear aspect from the manifold specificity. We then tackle the resulting
      constrained optimization problem via Augmented Lagrange Multipliers. The strength
      and the novelty of our approach is that this framework can seamlessly handle
      different computer vision problems. The algorithm is such that only a projector
      onto the manifold constraint is needed. We present experiments and results for
      some popular factorization problems in computer vision such as rigid, non-rigid,
      and articulated Structure from Motion, photometric stereo, and 2D-3D non-rigid
      registration.

PMID- 22156103
TI  - Robust and efficient ridge-based palmprint matching.
AB  - During the past decade, many efforts have been made to use palmprints as a
      biometric modality. However, most of the existing palmprint recognition systems
      are based on encoding and matching creases, which are not as reliable as ridges.
      This affects the use of palmprints in large-scale person identification
      applications where the biometric modality needs to be distinctive as well as
      insensitive to changes in age and skin conditions. Recently, several ridge-based
      palmprint matching algorithms have been proposed to fill the gap. Major
      contributions of these systems include reliable orientation field estimation in
      the presence of creases and the use of multiple features in matching, while the
      matching algorithms adopted in these systems simply follow the matching
      algorithms for fingerprints. However, palmprints differ from fingerprints in
      several aspects: 1) Palmprints are much larger and thus contain a large number of
      minutiae, 2) palms are more deformable than fingertips, and 3) the quality and
      discrimination power of different regions in palmprints vary significantly. As a
      result, these matchers are unable to appropriately handle the distortion and
      noise, despite heavy computational cost. Motivated by the matching strategies of
      human palmprint experts, we developed a novel palmprint recognition system. The
      main contributions are as follows: 1) Statistics of major features in palmprints
      are quantitatively studied, 2) a segment-based matching and fusion algorithm is
      proposed to deal with the skin distortion and the varying discrimination power of
      different palmprint regions, and 3) to reduce the computational complexity, an
      orientation field-based registration algorithm is designed for registering the
      palmprints into the same coordinate system before matching and a cascade filter
      is built to reject the nonmated gallery palmprints in early stage. The proposed
      matcher is tested by matching 840 query palmprints against a gallery set of
      13,736 palmprints. Experimental results show that the proposed matcher
      outperforms the existing matchers a lot both in matching accuracy and speed.

PMID- 22156104
TI  - Analytic solutions of integral moving least squares for polygon soups.
AB  - This paper presents analytic solutions to the integral moving least squares (MLS)
      equations originally proposed by Shen et al. by choosing another specific
      weighting function that renders the numerator in the MLS equation unitless. In
      addition, we analyze the original method to show that their approximation
      surfaces (i.e., enveloping surfaces with nonzero values in the weighting
      function) often form zero isosurfaces near concavities behind the triangle-soup
      models. This paper also presents error terms for the integral MLS formulations
      against signed distance fields. Based on our analytic solutions, we show that our
      method provides both interpolation and approximation surfaces faster and more
      efficiently. Because our method computes solutions for integral MLS equations
      directly, it does not rely on numerical steps that might have numerical-accuracy
      issues. In particular, unlike the original method that deals with incorrect
      approximation surfaces by iteratively adjusting parameters, this paper proposes
      faster and more efficient approximations to surfaces without needing iterative
      routines. We also present computational efficiency comparisons, in which our
      method is 15-fold faster in computing integrations, even with conservative
      assumptions. Finally, we show that the surface normal vectors on the implicit
      surfaces formed by our analytic solutions are identical to the angle-weighted
      pseudonormal vectors.

PMID- 22156105
TI  - Unified Boundary-Aware Texturing for Interactive Volume Rendering.
AB  - In this paper, we describe a novel approach for applying texture mapping to
      volumetric data sets. In contrast to previous approaches, the presented technique
      enables a unified integration of 2D and 3D textures and thus allows to emphasize
      material boundaries as well as volumetric regions within a volumetric data set at
      the same time. One key contribution of this paper is a parametrization technique
      for volumetric data sets, which takes into account material boundaries and
      volumetric regions. Using this technique, the resulting parametrizations of
      volumetric data sets enable texturing effects which create a higher degree of
      realism in volume rendered images. We evaluate the quality of the parametrization
      and demonstrate the usefulness of the proposed concepts by combining volumetric
      texturing with volumetric lighting models to generate photorealistic volume
      renderings. Furthermore, we show the applicability in the area of illustrative
      visualization. 

PMID- 22156106
TI  - Parallel computation of 2D Morse-Smale complexes.
AB  - The Morse-Smale complex is a useful topological data structure for the analysis
      and visualization of scalar data. This paper describes an algorithm that
      processes all mesh elements of the domain in parallel to compute the Morse-Smale
      complex of large 2D datasets at interactive speeds. We employ a reformulation of
      the Morse-Smale complex using Forman's Discrete Morse Theory and achieve
      scalability by computing the discrete gradient using local accesses only. We also
      introduce a novel approach to merge gradient paths that ensures accurate geometry
      of the computed complex. We demonstrate that our algorithm performs well on both
      multicore environments and on massively parallel architectures such as the GPU.

PMID- 22156107
TI  - Co-located collaborative visual analytics around a tabletop display.
AB  - Co-located collaboration can be extremely valuable during complex visual
      analytics tasks. We present an exploratory study of a system designed to support
      collaborative visual analysis tasks on a digital tabletop display. Fifteen
      participant pairs employed Cambiera, a visual analytics system, to solve a
      problem involving 240 digital documents. Our analysis, supported by observations,
      system logs, questionnaires, and interview data, explores how pairs approached
      the problem around the table. We contribute a unique, rich understanding of how
      users worked together around the table and identify eight types of collaboration
      styles that can be used to identify how closely people work together while
      problem solving. We show how the closeness of teams' collaboration and
      communication influenced how they performed on the task overall. We further
      discuss the role of the tabletop for visual analytics tasks and derive design
      implications for future co-located collaborative tabletop problem solving
      systems.

PMID- 22156108
TI  - The effective depth of cylindrical ionization chambers in water for clinical
      proton beams.
AB  - In this study, we have developed an explicit analytical model to compute the
      effective depth of cylindrical ionization chambers in water for clinical proton
      beams.We have compared our explicit analytical model with an existing series
      expansion model. We have calculated the shift of water equivalent depth for
      different cylindrical ionization chambers and have compared our results with the
      IAEA recommendations and series expansion model. We have developed a method to
      compute the elliptic integral in an explicit analytical form. Using this integral
      form, the shift of the water equivalent depth has been computed by accounting for
      individual contributions of the ionization chamber cavity, wall, central
      electrode and sleeve for proton energies ranging from 1.0 keV to 1.0 GeV for 34
      commercially available ionization chambers. The comparison of an explicit
      analytical expression with a series expansion reveals that integrations
      calculated by the series expansion fail to converge to a precise value when the
      ratio of radii of cylindrical ionization chambers is greater than 0.5. For all
      the ion chambers selected in this study, our results vary at a maximum of 0.5 mm
      from the IAEA recommendations, whereas the maximum variation for the series
      expansion model is 1.5 mm. The findings of this study suggest that the developed
      analytical model is reliable for the calculation of the effective depth in water.
      Furthermore, the verification of these results with Monte Carlo calculation may
      suggest the need for a review of the standards for all commercial ionization
      chambers.

PMID- 22156109
TI  - Quantum spin fluctuations in the spin-liquid state of Tb2Ti2O7.
AB  - Neutron scattering experiments on a polycrystalline sample of the frustrated
      pyrochlore magnet Tb(2)Ti(2)O(7), which does not show any magnetic order down to
      50 mK, have revealed that it shows condensation behavior below 0.4 K from a
      thermally fluctuating paramagnetic state to a spin-liquid ground state with
      quantum spin fluctuations. Energy spectra change from quasielastic scattering to
      a continuum with a double-peak structure at energies of 0 and 0.8 K in the spin
      liquid state. Specific heat shows an anomaly at the crossover temperature.

PMID- 22156110
TI  - Natural language processing with dynamic classification improves P300 speller
      accuracy and bit rate.
AB  - The P300 speller is an example of a brain-computer interface that can restore
      functionality to victims of neuromuscular disorders. Although the most common
      application of this system has been communicating language, the properties and
      constraints of the linguistic domain have not to date been exploited when
      decoding brain signals that pertain to language. We hypothesized that combining
      the standard stepwise linear discriminant analysis with a Naive Bayes classifier
      and a trigram language model would increase the speed and accuracy of typing with
      the P300 speller. With integration of natural language processing, we observed
      significant improvements in accuracy and 40-60% increases in bit rate for all six
      subjects in a pilot study. This study suggests that integrating information about
      the linguistic domain can significantly improve signal classification.

PMID- 22156111
TI  - Size controlled synthesis of biocompatible gold nanoparticles and their activity
      in the oxidation of NADH.
AB  - Size and shape controlled synthesis remains a major bottleneck in the research on
      nanoparticles even after the development of different methods for their
      preparation. By tuning the size and shape of a nanoparticle, the intrinsic
      properties of the nanoparticle can be controlled leading tremendous potential
      applications in different fields of science and technology. We describe a facile
      route for the one pot synthesis of gold nanoparticles in water using monosodium
      glutamate as the reducing and stabilizing agent in the absence of seed particles.
      The particle diameter can be easily controlled by varying the pH of the reaction
      medium. Nanoparticles were characterized using scanning electron microscopy, UV
      vis absorption spectroscopy, cyclic voltammetry, and dynamic light scattering.
      Zeta potential measurements were made to compare the stability of the different
      nanoparticles. The results suggest that lower pH favours a nucleation rate giving
      rise to smaller particles and higher pH favours a growth rate leading to the
      formation of larger particles. The synthesized nanoparticles are found to be
      stable and biocompatible. The nanoparticles synthesized at high pH exhibited a
      good electrocatalytic activity towards oxidation of nicotinamide adenine
      dinucleotide (NADH).

PMID- 22156112
TI  - Comment on 'implications on clinical scenario of gold nanoparticle
      radiosensitization in regard to photon energy, nanoparticle size, concentration
      and location'.
AB  - A recent paper by Lechtman et al (2011 Phys. Med. Biol. 56 4631-47) presented
      Monte Carlo modelling of gold nanoparticle dose modification. In it, they predict
      that the introduction of gold nanoparticles has the strongest effect with x-rays
      at kilovoltage energies, and that negligible increases in dose are expected at
      megavoltage energies. While these results are in agreement with others in the
      literature (including those produced by our group), the conclusion that '(gold
      nanoparticle) radiosensitization using a 6 MV photon source is not clinically
      feasible' appears to conflict with recently published experimental studies which
      have shown radiosensitization using 6 MV x-ray sources with relatively low gold
      concentrations. The increasing disparity between theoretical predictions of dose
      enhancement and experimental results in the field of gold nanoparticle
      radiosensitization suggests that, while the ability of gold nanoparticles to
      modify dose within a tumour volume is well understood, the resulting
      radiosensitization is not simply correlated with this measure. This highlights
      the need to validate theoretical predictions of this kind against experimental
      measurements, to ensure that the scenarios and values being modelled are
      meaningful within a therapeutic context.

PMID- 22156113
TI  - Temperature and bath size in exact diagonalization dynamical mean field theory.
AB  - Dynamical mean field theory (DMFT), combined with finite-temperature exact
      diagonalization, is one of the methods used to describe electronic properties of
      strongly correlated materials. Because of the rapid growth of the Hilbert space,
      the size of the finite bath used to represent the infinite lattice is severely
      limited. In view of the increasing interest in the effect of multi-orbital and
      multi-site Coulomb correlations in transition metal oxides, high-T(c) cuprates,
      iron-based pnictides, organic crystals, etc, it is appropriate to explore the
      range of temperatures and bath sizes in which exact diagonalization provides
      accurate results for various system properties. On the one hand, the bath must be
      large enough to achieve a sufficiently dense level spacing, so that useful
      spectral information can be derived, especially close to the Fermi level. On the
      other hand, for an adequate projection of the lattice Green's function onto a
      finite bath, the choice of the temperature is crucial. The role of these two key
      ingredients in exact diagonalization DMFT is discussed for a wide variety of
      systems in order to establish the domain of applicability of this approach. Three
      criteria are used to illustrate the accuracy of the results: (i) the convergence
      of the self-energy with the bath size, (ii) the quality of the discretization of
      the bath Green's function, and (iii) comparisons with complementary results
      obtained via continuous-time quantum Monte Carlo DMFT. The materials comprise a
      variety of three-orbital and five-orbital systems, as well as single-band Hubbard
      models for two-dimensional triangular, square and honeycomb lattices, where non
      local Coulomb correlations are important. The main conclusion from these examples
      is that a larger number of correlated orbitals or sites requires a smaller number
      of bath levels. Down to temperatures of 5-10 meV (for typical bandwidths W ~ 2
      eV) two bath levels per correlated impurity orbital or site are usually adequate.

PMID- 22156114
TI  - Welfare reform and older immigrant adults' Medicaid and health insurance
      coverage: changes caused by chilling effects of welfare reform, protective
      citizenship, or distinct effects of labor market condition by citizenship?
AB  - OBJECTIVES: To examine how federal noncitizen Medicaid eligibility restriction
      and generous state policy affect Medicaid and health insurance coverage among
      older adults with different citizenship status. METHOD: This study uses an older
      adult sample (65 years or older) from the Current Population Survey (CPS) and
      state data and employed a triple difference-in-differences approach to
      incorporate variations in citizenship status, time, and state eligibility.
      RESULTS: Findings show that Medicaid coverage significantly declined among older
      noncitizens but increased among older naturalized citizens after Welfare Reform.
      Findings also show that the differences in older noncitizens' health insurance
      coverage changes were significant between generous and nongenerous states.
      DISCUSSION: Medicaid eligibility affects older immigrant adults' Medicaid and
      health insurance coverage. Findings support the "protective citizenship"
      hypothesis but not the "chilling effect" and "labor market condition" hypotheses.
      Opposite patterns of change in Medicaid coverage between naturalized citizens and
      noncitizens raise doubt about the effectiveness of eligibility restrictions in
      reducing government spending.

PMID- 22156115
TI  - Degradation characteristics of polylactide in thermophilic anaerobic digestion
      with hyperthermophilic solubilization condition.
AB  - To test whether hyperthermophilic treatment promotes polylactide (PLA)
      dissolution and methane conversion under anaerobic digestion conditions, a single
      thermophilic control reactor (55  degrees C) and a two-phase system consisting of
      a hyperthermophilic reactor (80  degrees C) and a thermophilic reactor (55 
      degrees C) were continuously fed with a mixture of PLA and artificial kitchen
      garbage. In Runs 1 and 2, the PLA dissolution ratios in the two-phase system were
      79.2 +/- 6.5% and 85.2 +/- 7.0%, respectively, higher than those of the control.
      Batch experimental results indicated that hyperthermophilic treatment could
      promote PLA dissolution to a greater degree as compared with single thermophilic
      treatment and that ammonia addition also had a promotional effect on PLA
      dissolution. In the two-phase system, after hyperthermophilic treatment,
      dissolved PLA was converted to methane gas under the subsequent thermophilic
      condition.

PMID- 22156116
TI  - Analysis of trends in water quality: constructed wetlands in metropolitan Taipei.
AB  - Meandering through the most densely populated metropolitan areas of Taipei,
      Taiwan, the Danshui River and its tributaries have undergone the construction of
      14 wetlands since 2004, as a means to improve water quality. This study was
      conducted to examine the functional capabilities associated with treating non
      point source pollution through these riparian wetlands. Trend analysis was used
      to differentiate dissolved oxygen, biochemical oxygen demand, suspended solids,
      ammonia, and Escherichia coli, among 13 sampling sites using both functions of a
      Mann-Kendall test and a seasonal Mann-Kendall test. The results show that water
      quality in Taipei metropolitan rivers has been improving since increasing the
      number of constructed wetlands and connecting households to the public sewage
      system. The concentration of pollutants such as those influencing biochemical
      oxygen demand have gradually declined in drought seasons because riparian
      wetlands contribute a base flow to dilute riverine pollutants. This paper
      indicates that the creation of treatment systems influences dissolved oxygen
      conditions at the municipal scale, suggesting that constructed wetlands could
      stabilize water quality during extreme hydrological events and improve water
      quality particularly in times of drought.

PMID- 22156118
TI  - Calculation methods to perform mass balance of endocrine disrupting compounds in
      a submerged membrane bioreactor: fate and distribution of estrogens during the
      biological treatment.
AB  - The purpose of this paper is to report the study of the fate and distribution of
      three endocrine disrupting compounds (estrogens); Estrone (E1), 17beta-estradiol
      (E2), and 17alpha-ethinylestradiol (EE2) in a laboratory scale submerged membrane
      bioreactor (SMBR). For this matter, both aqueous and solids phases were analyzed
      for the presence of E1, E2 and EE2. The outcome of this study was that three
      SMBRs showed enhanced elimination of estrogens in different operational
      conditions; the estrogen removal was close to 100% in SMBR. Additionally, E1, E2
      and EE2 were detected in SMBR sludge at concentrations of up to 41.2, 37.3 and
      36.9 ng g(-1) dry weight, respectively. The estrogen removal in the SMBRs was
      directly influenced by a combination of simultaneous biodegradation-adsorption
      processes, indicating that the main removal mechanism of the estrogens in the
      SMBRs is the biodegradation process. The E1, E2 and EE2 were biologically
      degraded in the SMBR (87-100%). The sorption of estrogens onto activated sludge
      was from 2%. Therefore, a high potential for estrogen removal by biodegradation
      in the SMBR was observed, allowing less estrogen concentration in the dissolved
      phase available for the adsorption of these compounds onto biological flocs. Two
      different methods were carried out for mass balance calculations of estrogens in
      SMBR. For the first method, the measured data was used in both liquid and solid
      phases, whereas for the second one, it was in aqueous phase and solid-water
      distribution coefficients (K(d)) value of E1, E2 and EE2. The purpose of these
      methodologies is to make easier the identification of the main mechanisms
      involved in the removal of E1, E2 and EE2 in a SMBR. Both methods can be applied
      in order to determine the mechanism, fate and distribution of estrogens in a
      SMBR.

PMID- 22156117
TI  - Chlorine disinfection of Pseudomonas aeruginosa, total coliforms, Escherichia
      coli and Enterococcus faecalis: revisiting reclaimed water regulations.
AB  - Pathogenic organisms can be transmitted orally through drinking water or through
      skin and mucosae by both direct and indirect contact, and their presence in water
      thus has a negative impact on public health. In wastewater treatment plants
      (WWTP), water is disinfected to inactivate pathogens. The quantification of
      several microbial indicators in aquatic systems is required to estimate the
      biological quality of such systems. So far, coliform bacteria have been used as
      traditional indicators world-wide. This study has assessed the resistance of
      total coliforms, Escherichia coli, Pseudomonas aeruginosa and Enterococcus
      faecalis to three dosages of sodium hypochlorite (NaClO) at two exposure times.
      The bacteria were isolated from secondary effluents of a WWTP located in Hidalgo,
      Mexico. The results show that the number of colony-forming units of all studied
      bacterial types decreased when both the NaClO concentration and exposure times
      increased. However, they were not eliminated. The inclusion of the species
      Pseudomonas aeruginosa in regulations for treated wastewater quality as a new
      indicator is highly recommended due to its importance as an opportunistic
      pathogen. The detection of this species along with the traditional organisms
      could be particulary significant for reclaimed water to be used with direct human
      contact.

PMID- 22156119
TI  - Influence of operating conditions on ceramic ultrafiltration membrane performance
      when treating textile effluents.
AB  - This work studies the performance of three commercial ceramic ultrafiltration
      membranes (ZrO(2)-TiO(2)) treating raw effluent from a textile industry. The
      effect of crossflow velocity at 3, 4 and 5 m s(-1) as well as membrane
      characteristics, such as molecular weight cut-off (30, 50 and 150 kDa), on
      process performance were studied. Experiments were carried out in concentration
      mode in order to observe the effect of volume reduction factor simultaneously.
      Results showed a combined influence of both crossflow velocity and molecular
      weight cut-off on flux performance. TOC and COD removals up to 70% and 84%
      respectively were reached. On the other hand, almost complete color (>97%) and
      turbidity (>99%) removals were achieved for all the membranes and operating
      conditions.

PMID- 22156120
TI  - Experimental study of a novel hybrid constructed wetland for water reuse and its
      application in Southern China.
AB  - A new type of hybrid constructed wetland (CW), consisting of both vertical
      baffled flow wetland (VBFW) and horizontal subsurface flow wetland (HSFW), has
      been deployed in Southern China to naturally accelerate the removal of organic
      matter and nitrogen. The hybrid CW system is characterised by a combination of
      continuous baffled flow vertical wetland and 'S' pattern horizontal subsurface
      flow wetland with natural aeration ditches to increase the concentration of
      dissolved oxygen in the HSFW bed. An internal circulatory system from the HSFW
      effluent back to the VBFW may optionally be operated to enhance the biological
      denitrification effect. Cyperus alternifolius is the main macrophyte in the
      wetland bed. The performance of the hybrid CW was studied with a pilot-scale
      system and three full-scale systems for municipal sewage treatment in Southern
      China. The results suggest that this new hybrid CW can achieve removal
      efficiencies of chemical oxygen demand, suspended solids, ammonia nitrogen, total
      nitrogen, and total phosphorus of better than 83.6, 95.0, 71.7, 64.5 and 68.1%
      respectively, with a specific wetland bed area of 0.70-0.93 m(2) PE(-1). The mean
      effluent concentrations of these parameters would meet the regulatory discharge
      limits for wastewater treatment systems (GB18918, 2002) and reuse in the context
      of agricultural irrigation solutions in China.

PMID- 22156121
TI  - Application of nitrogen and phosphorus criteria for streams in agricultural
      landscapes.
AB  - Efforts to control eutrophication of water resources in agriculturally dominated
      ecosystems have focused on managing on-farm activities to reduce nutrient loss;
      however, another management measure for improving water quality is adoption of
      environmental performance criteria (or 'outcome-based standards'). Here, we
      review approaches for setting environmental quality criteria for nutrients,
      summarize approaches developed in Canada for setting 'ideal' and 'achievable'
      nutrient criteria for streams in agricultural watersheds, and consider how such
      criteria could be applied. As part of a 'National Agri-Environmental Standards
      Initiative', the Government of Canada committed to the development of non
      regulatory environmental performance standards that establish total P (TP) and
      total N (TN) concentrations to protect ecological condition of agricultural
      streams. Application of four approaches for defining ideal standards using only
      chemistry data resulted in values for TP and TN spanning a relatively narrow
      range of concentrations within a given ecoregion. Cross-calibration of these
      chemically derived standards with information on biological condition resulted in
      recommendations for TP and TN that would likely protect aquatic life from adverse
      effects of eutrophication. Non-point source water quality modelling was then
      conducted in a specific watershed to estimate achievable standards, i.e. chemical
      conditions that could be attained using currently available and recommended
      management practices. Our research showed that, taken together, short-term
      achievable standards and ultimate ideal standards could be used to set policy
      targets that should, if realized, lower N and P concentrations in Canadian
      agricultural streams and improve biotic condition.

PMID- 22156122
TI  - Layered double hydroxide (LDH)-coated attapulgite for phosphate removal from
      aqueous solution.
AB  - In this study, a composite adsorbent, layered double hydroxide (LDH)-coated
      attapulgite (LDH-AP), was synthesized and characterized. Its potential
      application for LDH stabilizer and phosphate (P) removal from aqueous solution
      was evaluated using the batch mode and continuous mode in a packed bed column.
      The batch experiments revealed that the data of P adsorption onto LDH-AP could be
      well described by the Freundlich equation, and the maximum adsorption capacity
      was estimated to be 6.9 mg/g. The column experiments were conducted in the tap
      water and the results indicated that the competing anions could slightly decrease
      phosphate removal. The saturated column was regenerated by 0.2 mol/L of NaOH and
      the regenerated column was examined for its reuse in phosphate removal. The
      results of this study suggested that attapulgite could be used as an applicable
      stabilizer of LDH and LDH-AP could be potentially used as a promising filtration
      medium for phosphate removal.

PMID- 22156123
TI  - A framework for considering externalities in urban water asset management.
AB  - Urban communities rely on a complex network of infrastructure assets to connect
      them to water resources. There is considerable capital investment required to
      maintain, upgrade and extend this infrastructure. As the remit of a water utility
      is broader than just financial considerations, infrastructure investment
      decisions must be made in light of environmental and societal issues. One way of
      facilitating this is to integrate consideration of externalities into decision
      making processes. This paper considers the concept of externalities from an asset
      management perspective. A case study is provided to show the practical
      implications to a water utility and asset managers. A framework for the inclusion
      of externalities in asset management decision making is also presented. The
      potential for application of the framework is highlighted through a brief
      consideration of its key elements.

PMID- 22156124
TI  - Field survey of pollutants discharged from different types of residential area in
      the Yamuna River Basin, India.
AB  - The Ganges River, one of the most heavily populated and urbanized river basins in
      Asia, is polluted by increasing wastewater influent and water-borne diseases are
      caused in the metropolitan area. This study focused on the Yamuna River, a major
      tributary of the Ganges. We determined the pollutant load per unit of urban area
      classified by the income of the residents to help design an appropriate sewerage
      system. In addition, a simple method of estimating runoff pollutant load was
      examined using data on pollutant load per unit and runoff coefficient.

PMID- 22156125
TI  - Performance of an in-situ rotating biological contactor in a recirculating
      aquaculture system.
AB  - The start-up and activation of a nitrifying rotating biological contactor (RBC)
      and its performance inside a culture tank of rainbow trout were studied. First,
      in a lab-scale operation, the system was fed with a synthetic medium containing a
      high ammonia concentration (567 mg NH(4)(+)-N L(-1)) and operated at a high
      hydraulic retention time (HRT) (6.5 days) to minimize the wash-out of the biomass
      and promote the biofilm formation. Then, both inlet ammonia concentration and HRT
      were decreased in order to obtain operational conditions similar to those of the
      culture tank. During this period, the RBC was able to treat an ammonia loading
      rate (ALR) of 0.64 g N-NH(4)(+) L(-1) d(-1) with a removal efficiency within 70
      100%. Pilot-scale experiments were carried out in culture tanks of rainbow trout.
      The operation of a recirculating system with the RBC unit was compared with a
      recirculating system without biological treatment and with a flow-through system.
      The use of this in-situ nitrifying unit allowed working at a recirculation ratio
      of 90% without negative effects on either growth or the condition factor of
      fishes. Up to 70% of ammonia generated was removed and a removal rate of 1.41 g
      NH(4)(+)-N m(-2) d(-1) was reached.

PMID- 22156126
TI  - Preparation and characterization of fouling-resistant composite membranes based
      on layer-by-layer self-assembly technique.
AB  - This paper introduces a versatile approach for surface modification of 621
      terylene filtration fabric (FF) self-assembled by a dynamic layer-by-layer
      technique. The hexadecyl trimethyl ammonium bromide (HTAB) and cross-linked
      polyvinyl alcohol microspheres (PVA-MS) were alternatively deposited on support
      membrane under a pressure of 0.01 MPa to modify FF. Morphological changes and
      hydrophilicity of the modified FF were characterized in detail by scanning
      electron micrograph and water contact angle measurements. Results revealed that
      PVA-MS could be adsorbed mainly on the surface of FF and water contact angle
      decreased with the increase of HTAB/PVA-MS bilayer numbers indicating an enhanced
      hydrophilicity for the modified FF. Backwash experiments of the modified FF
      exhibited much higher stability of PVA-MS. Protein adsorption experiments were
      conducted to evaluate the antifouling property of the modified FF. Results
      indicated that protein adsorption of the membrane surface could be obviously
      improved by modification, which exhibited superior antifouling property of the
      modified FF.

PMID- 22156127
TI  - Removal of pharmaceuticals using combination of UV/H(2)O(2)/O(3) advanced
      oxidation process.
AB  - Water and wastewater effluents contain a vast range of pharmaceutical chemicals.
      The present study aims to determine the potential of the advanced oxidation
      technology UV/H(2)O(2)/O(3) and its sub-processes (i.e. UV, UV/H(2)O(2), UV/O(3),
      O(3) and H(2)O(2)/O(3)) for the degradation of the antibiotics ciprofloxacin
      (CIP) and trimethoprim (TMP), and the antineoplastic drug cyclophosphamide (CPD)
      from water. Creating AOP conditions improved in most cases the degradation rate
      of the target compounds (compared with O(3) and UV alone). H(2)O(2) concentration
      was found to be an important parameter in the UV/H(2)O(2) and H(2)O(2)/O(3) sub
      processes, acting as (*)OH initiator as well as (*)OH scavenger. Out of the
      examined processes, O(3) had the highest degradation rate for TMP and
      H(2)O(2)/O(3) showed highest degradation rate for CIP and CPD. The electrical
      energy consumption for both CIP and CPD, as calculated using the E(EO) parameter,
      was in the following order: UV > UV/O(3) > UV/H(2)O(2)/O(3) > O(3) >
      H(2)O(2)/O(3). Whereas for TMP O(3) was shown to be the most electrical energy
      efficient. Twelve degradation byproducts were identified following direct UV
      photolysis of CIP.

PMID- 22156128
TI  - Characterization and degradation process of sludge profiles inside a facultative
      pond (Patagonia, Argentina).
AB  - To investigate the characteristics and degradation process in sludge profile,
      three sampling sessions were made in three different places inside the primary
      facultative pond of Puerto Madryn city, which was located in a region with a
      temperate climate in coastal Patagonia (Argentina). The sludge showed an
      extremely negative redox potential (between -441 and -282 mV) and elevated water
      content and organic matter concentration, ranging from 83.3 to 97.1% for porosity
      and from 22.5 to 64.4% for organic matter. The surface layer at the Outlet
      station during the summer showed the greatest concentration of pigments, reaching
      a maximum value of 10.6 mg/g for chlorophyll-a and 40.9 mg/g for phaeophytin, and
      a fast diminution with sediment depth. The important concentration of pigment in
      the surface layer, coincident with phytoplankton bloom in the water column, could
      support the importance of nitrogen removal via uptake and organic sedimentation
      in the water column. In warm months the degradation rate was clear, as reflected
      in a decrease in sediment layer, and even part of the clay bottom was captured
      inside an 8 cm core sample, registering extremely low concentrations of pigments,
      carbohydrates, proteins and lipids. The season and the degree of treatment have
      an influence on sludge characteristics and the organic matter degradation
      process.

PMID- 22156129
TI  - Monitoring the nitrification and identifying the endpoint of ammonium oxidation
      by using a novel system of titrimetry.
AB  - Based on the structure of the hybrid respirometer previously developed in our
      group, a novel implementation for titrimetry was developed, in which two pH
      electrodes were installed at the inlet and outlet of the measuring cell. The
      software capable of digital filtering and titration time delay correction was
      developed in LabVIEW. The hardware and software of the titrimeter and the
      respirometer were integrated to construct a novel system of respirometry
      titrimetry. The system was applied to monitor a batch nitrification process. The
      obtained profiles of oxygen uptake rate (OUR) and hydrogen ion production rate
      (HPR) are consistent with each other and agree with the principle of the
      biological nitrification reaction. According to the OUR and HPR measurements, the
      oxidized ammonium concentrations were estimated accurately. Furthermore, the
      endpoint of ammonium oxidation was identified with much higher sensitivity by the
      HPR measurement. The system could be potentially used for on-line monitoring of
      biochemical reactions occurring in any kind of bioreactors because its measuring
      cell is completely independent of the bioreactor.

PMID- 22156130
TI  - Power generation in MFCs with architectures based on tubular cathodes or fully
      tubular reactors.
AB  - Tubular cathodes provide a method to obtain high surface areas for scaling up
      microbial fuel cells (MFCs), but the importance of the cathode shape is not
      known. We therefore examined power production using cathodes in various
      configurations (tubes or flat). The MFC with a single internal carbon cloth tube
      cathode (71 W/m(3)) produced more power than previously obtained with an
      ultrafiltration membrane (8 W/m(3)) due to the better performance of carbon
      material. This power density was slightly less than that of a flat carbon cloth
      cathode (81 W/m(3); 88 m(2)/m(3)) due to the lower total surface area of the tube
      (68 m(2)/m(3)) and not as a result of the tubular cathode shape. Adding a second
      tube increased power (83 W/m(3)) in proportion to specific surface area (93
      m(2)/m(3)). Wrapping the cathode completely around the anode formed a fully
      tubular MFC (external tubular reactor) with a higher surface area that produced
      128 W/m(3). Volumetric power density was highly correlated with cathode specific
      surface area (R(2) = 0.93, p = 0.008) and did not depend on the cathode shape
      (tubes, completely tubular, or flat). Thus, future MFC designs should focus on
      increasing cathode specific surface area.

PMID- 22156131
TI  - Quantification of dissolved methane in UASB reactors treating domestic wastewater
      under different operating conditions.
AB  - This paper aimed at measuring the concentration of methane dissolved in effluents
      from different UASB reactors (pilot-, demo- and full-scale) treating domestic
      wastewater, in order to calculate the degree of saturation of such greenhouse gas
      and evaluate the losses of energetic potential in such systems. The results
      showed that methane saturation degrees, calculated according to Henry's law,
      varied from ~1.4 to 1.7 in the different reactors, indicating that methane was
      oversaturated in the liquid phase. The overall results indicated that the losses
      of dissolved methane in the anaerobic effluents were considerably high, varying
      from 36 to 41% of total methane generated in the reactor. These results show that
      there is considerable uncontrolled loss of methane in anaerobic wastewater
      treatment plants, implying the need of research on technologies aimed at
      recovering such energetic greenhouse gas.

PMID- 22156132
TI  - Microbial community composition and reactor performance during hydrogen
      production in a UASB reactor fed with raw cheese whey inoculated with compost.
AB  - This study investigated the microbial community developed in a UASB reactor for
      hydrogen production and correlated it to reactor performance. The reactor was
      inoculated with kitchen waste compost and fed with raw cheese whey at two organic
      loading rates, 20 gCOD/Ld and 30 gCOD/Ld. Hydrogen production was very variable,
      using an OLR of 30 gCOD/Ld averaged 1.0 LH(2)/Ld with no methane produced under
      these conditions. The hydrogen yield was also very variable and far from the
      theoretical. This low yield could be explained by selection of a mixed
      fermentative population with presence of hydrogen producing organisms
      (Clostridium, Ruminococcus and Enterobacter) and other non-hydrogen producing
      fermenters (Lactobacillus, Dialister and Prevotella). The molecular analysis of
      the raw cheese whey used for feeding revealed the presence of three predominant
      organisms that are affiliated with the genera Buttiauxella (a low-yield hydrogen
      producer) and Streptococcus (a lactic acid-producing fermenter). Although these
      organisms did not persist in the reactor, the continuous addition of these
      fermenters could decrease the reactor's hydrogen yield.

PMID- 22156133
TI  - Removal of cyanide from acrylonitrile wastewater using gas membrane.
AB  - Acrylonitrile wastewater is one of the most refractory industrial wastewaters as
      it contains cyanide at a high concentration. This study introduced a safe,
      effective and economic strategy, that is, use of the gas membrane to
      acrylonitrile wastewater treatment. Due to the complicated constituents of
      acrylonitrile wastewater, cyanide removal rate by gas membrane is very low. In
      order to enhance HCN removal, the operational conditions were optimized; pre
      treatment strategies for fouling mitigation were also proposed and tested for
      acrylonitrile wastewater. The optimal operational parameters were achieved at an
      acidified pH of 5.0, wastewater velocity of 0.14 m s(-1), NaOH concentration of
      10% and a temperature of 40  degrees C. The major factor affecting HCN removal
      was the pH of the acidified wastewater. The reason for the low removal rate was
      further explored and found to be the decrease of HCN transfer coefficient, which
      was caused by membrane fouling. Furthermore, the predominant foulants have been
      identified as colloidal organic materials and inorganic salts. Alkalization,
      which is effective in reducing these materials, has been proven to be most
      effective in mitigating membrane fouling and improving HCN removal, which was
      also confirmed by a pilot-scale study. The overall removal rate was therefore
      significantly enhanced to 87.1%.

PMID- 22156134
TI  - Effects of sludge retention time and biosurfactant on the treatment of
      polyaromatic hydrocarbon (PAH) in a petrochemical industry wastewater.
AB  - A laboratory-scale aerobic activated sludge reactor (AASR) system was employed to
      investigate the effects of sludge retention time (SRT) on the removal of three
      polyaromatic hydrocarbons (PAHs) with low benzene rings [(acenaphthene (ACT),
      fluorene (FLN) and phenanthrene (PHE)] and six PAHs with high benzene rings
      [(benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP),
      indeno[1,2,3-cd]pyrene, dibenz[a,h]anthracene (DahA), benzo[g,h,i]perylene
      (BghiP)] in the presence of rhamnolipid (RD), emulsan (EM) and surfactine (SR)
      biosurfactants. This study showed that biosurfactants enhance the PAH
      biodegradation by increasing the biomass growth. RD exhibits a better performance
      than the other biosurfactants in the removal of the chemical oxygen demand (COD)
      and PAHs. At a RD concentration of 15 mg/L aerobic treatment for 25 days, SRT was
      enough to remove over 95% of total PAHs, and COD(dis). Under the same conditions
      75% of COD originating from the inert organics (COD(inert)) and 96% of COD
      originating from the inert soluble microbial products (COD(imp)) were removed. At
      25 days SRT and 15 mg/L RD concentration, about 88% of PAHs were biodegraded by
      the AASR system, 4% were accumulated in the system, 3% were released in the
      effluent, and 5% remained in the waste sludge.

PMID- 22156135
TI  - Investigation of microbial safety of a full-scale ozonation and biological
      activated carbon process under high humidity and temperature conditions.
AB  - Microbial safety of a full-scale ozonation and biological activated carbon (BAC)
      process was investigated by examining pathogens, microbial community and particle
      counts, with emphasis on the BAC effluent. The process is located at South China,
      where the average humidity and air temperature were 70-80% and 22-24  degrees C,
      respectively. A high diversity of microbial community existed on the BAC media.
      Three types of dominant bacteria were identified, including Chryseobacterium
      indologenes, Bacillus brevis and Pseudomonas stutzeri, accounting for 90-95% of
      total bacteria number. As to pathogenic bacteria and viruses, an opportunistic
      pathogen, Bacillus cereus, was detected on the BAC. Six types of invertebrates
      were also observed on the medium, including rotifer, cyclops, nematode,
      clodecera, nauplius and blood worm. Diversity and number of invertebrates in the
      BAC effluent were higher than those in the BAC influent. Particle counts were
      generally less than 50 CNT/mL, with the maximum of 500 CNT/mL during the initial
      filtration stage after backwashing.

PMID- 22156136
TI  - Influence of hydraulic retention time on UASB post-treatment with UF membranes.
AB  - A pilot UASB reactor coupled with an external ultrafiltration (UF) membrane was
      operated under three different hydraulic retention times (HRT) for domestic
      wastewater treatment. The aim was to assess the HRT influence on system
      performance and fouling. The highest concentrations of COD, total solids,
      extracellular polymeric substances (EPS) and soluble microbial products (SMP) in
      UASB effluent and permeate were found when the UASB reactor was operated under
      the lowest HRT studied (4 hours); although the fulfillment of Mexican Standard
      for wastewater reclamation was not compromised. This fact could be attributed to
      the higher shear stress forces inside the UASB reactor when it was operated at
      low HRT, which promoted the release of biopolymeric substances in its effluent.
      Besides, the fouling propensity in the UASB effluent was worsened with HRT
      reduction, by increasing the fouling rate and the specific cake resistance. Based
      on these results, it is recommended to avoid operating the UASB reactor at low
      HRTs (less than 4 hours) in order to control SMP and EPS fouling potential. The
      results presented also suggest that HRT reduction has a detrimental effect on
      performance and fouling.

PMID- 22156137
TI  - Microbial diversity and community composition in recirculating vertical flow
      constructed wetlands.
AB  - Microorganisms constitute a central component of constructed wetlands (CWs),
      playing a major role in these systems' capacity for treating wastewater. The aim
      of this study was to determine the diversity and composition of the microbial
      community found in a recirculating vertical flow CW (RVFCW) bed fed with
      primarily settled domestic wastewater and its response to the presence of plants,
      season and location in the bed. The RVFCW removed 90-95% of TSS and BOD(5) to
      below 10 mg L(-1). The effluent quality was not significantly affected by
      seasonal temperature or the existence of plants in the bed. None of these factors
      had discernible effects on bacterial diversity, e.g. in the planted RVFCW, the
      richness (S') and Shannon-Weiner diversity (H') indices were 18.3 (+/-3.5) and
      2.49 (+/-0.15), respectively, which are similar to the values of 19.4 (+/-3.5)
      and 2.57 (+/-0.18) in the unplanted RVFCW. However, there were indications that
      the structure of the microbial community underwent changes that were uncorrelated
      with the environmental factors tested and that did not affect the overall
      performance. The consistency in diversity and composition/structure of the
      bacterial community in the face of temporal and environmental influences possibly
      contributes to the robustness and high treatment capacity of the RVFCW system.

PMID- 22156138
TI  - A method for extracting drainage networks with heuristic information from digital
      elevation models.
AB  - Depression filling and direction assignment over flat areas are critical issues
      in hydrologic analysis. This paper proposes a method to handle depressions and
      flat areas in one procedure. Being different from the traditional raster
      neighbourhoods processing with little heuristic information, the method is
      designed to compensate for the inadequate searching information of other methods.
      The proposed method routes flow through depressions and flat areas by searching
      for the outlet using the heuristic information. Heuristic information can reveal
      the general trend slope of the DEM (digital elevation models) and help the
      proposed method find the outlet accurately. The method is implemented in Pascal
      and experiments are carried out on actual DEM data. It can be seen from the
      comparison with the four existing methods that the proposed method can get a
      closer match result with the ground truth network. Moreover, the proposed method
      can avoid the generation of the unrealistic parallel drainage lines, unreal
      drainage lines and spurious terrain features.

PMID- 22156139
TI  - Importance of the order in enhancing EfOM removal by combination of BAC and
      MIEX((r)).
AB  - Biological activated carbon (BAC) is operationally a simple treatment which can
      be employed to remove effluent organic matter (EfOM) from secondary wastewater
      effluent (SWWE). Unfortunately, BAC removes only a limited amount of dissolved
      organic carbon (DOC). Thus, maximizing DOC removal from SWWE using BAC is a major
      concern in wastewater reuse. This study has investigated a hybrid system of BAC
      and Magnetic Ion Exchange Resin (MIEX((r))) for the enhanced removal of DOC.
      Performance of both BAC prior to MIEX((r)) (BAC/MIEX((r))) and reverse
      (MIEX((r))/BAC) combination was evaluated in terms of DOC removal. The
      BAC/MIEX((r)) showed much better DOC removal. This is because microbial activity
      in the BAC bed converted MIEX((r)) non-amenable DOC to MIEX((r)) amenable DOC. As
      a result, BAC/MIEX((r)) combination synergised DOC removal. In addition, BAC was
      also found to be highly effective in reducing MIEX((r)) dose for a given DOC
      removal from SWWE.

PMID- 22156141
TI  - A response surface model predicting the in vivo insertion behavior of
      micromachined neural implants.
AB  - The mechanical damage caused by the insertion of a foreign body into living
      tissue is inevitable, especially when a considerable stiffness mismatch is
      present, as in the case of micromachined neural implants and brain tissue.
      However, the response surface model based on a central composite experimental
      design described in this study showed that for particular configurations of the
      implant tip angle, width, thickness or insertion speed, some of these factors
      could be safely increased without causing an unwanted significant force or tissue
      dimpling increase. The model covers chisel tip angles between 10 degrees  and 50
      degrees , implant widths within the 200-400 um range and thicknesses between 50
      and 150 um. The insertion speed has been varied from 10 up to 100 um s(-1) to
      reach a final insertion depth of 6 mm. Coating the implant with parylene C proved
      to be beneficial in reducing the friction between the implant and the surrounding
      tissue. Successfully validated for a particular implant geometry, this model
      could be used as an insertion behavior prediction tool for the design
      optimization of future neural implants.

PMID- 22156142
TI  - Embedded layer of Ag nanoparticles prepared by a combined PECVD/PVD process
      producing SiOxCy-Ag nanocomposite thin films.
AB  - Structural properties of SiO(x)C(y)-Ag nanocomposite thin films prepared by a
      dual process PVD-PECVD in the same reactor have been investigated. The
      experimental results have demonstrated the influence of a PECVD process carried
      out at room temperature for the growth of a dielectric matrix on the size and the
      distribution density of Ag nanoparticles (NPs) deposited beforehand by magnetron
      sputtering. The plasma during the growth of the encapsulation SiO(x)C(y)  layer
      caused a diffusion of silver from NPs through the SiO(x)C(y)  matrix associated
      with a decrease in the average size of nanoparticles and an increase of their
      distribution density. Silver diffusion is blocked at a barrier interface to form
      a buried layer of individual Ag NPs which, for instance, can find plasmonic
      applications. Silver also diffuses toward the outer surface inducing
      antibacterial properties. In both cases initial Ag NPs act as reservoirs for
      multifunctional properties of advanced nanostructured films.

PMID- 22156143
TI  - Advancing density functional theory to finite temperatures: methods and
      applications in steel design.
AB  - The performance of materials such as steels, their high strength and formability,
      is based on an impressive variety of competing mechanisms on the
      microscopic/atomic scale (e.g. dislocation gliding, solid solution hardening,
      mechanical twinning or structural phase transformations). Whereas many of the
      currently available concepts to describe these mechanisms are based on empirical
      and experimental data, it becomes more and more apparent that further improvement
      of materials needs to be based on a more fundamental level. Recent progress for
      methods based on density functional theory (DFT) now makes the exploration of
      chemical trends, the determination of parameters for phenomenological models and
      the identification of new routes for the optimization of steel properties
      feasible. A major challenge in applying these methods to a true materials design
      is, however, the inclusion of temperature-driven effects on the desired
      properties. Therefore, a large range of computational tools has been developed in
      order to improve the capability and accuracy of first-principles methods in
      determining free energies. These combine electronic, vibrational and magnetic
      effects as well as structural defects in an integrated approach. Based on these
      simulation tools, one is now able to successfully predict mechanical and
      thermodynamic properties of metals with a hitherto not achievable accuracy.

PMID- 22156144
TI  - Experience with a two-tier reflex gFOBT/FIT strategy in a national bowel
      screening programme.
AB  - OBJECTIVES: To evaluate a two-tier reflex guaiac-based faecal occult blood test
      (gFOBT)/faecal immunochemical test (FIT) algorithm in screening for colorectal
      cancer. SETTING: Fourth screening round in NHS Tayside (Scotland). METHODS: gFOBT
      were sent to 50-74-year-olds. Participants with five or six windows positive were
      offered colonoscopy. Participants with one to four windows positive were sent a
      FIT and, if positive, were offered colonoscopy. Participants providing an
      untestable gFOBT were sent a FIT and, if positive, were offered colonoscopy.
      Outcomes following positive results, cancer stages and key performance indicators
      were assessed. RESULTS: Of 131,885 invited, 73,315 (55.6%) responded. There were
      66,957 (91.3%) negative, 241 (0.3%) strong positive, 5230 (7.1%) weak positive
      and 887 (1.2%) untestable results. The 241 participants who had five or six
      windows positive had more cancers than those positive by other routes: only 3 of
      the 30 cancers (9.7%) were Dukes' A. Among the 983 positive results from the weak
      positive gFOBT then positive FIT route, there were fewer cancers and more normal
      colonoscopies, but more adenomas than in the group with a strong positive gFOBT.
      In those with an untestable gFOBT, 77 had a positive FIT result, with fewer true
      and more false positive results than in the other groups. Fewer males had cancer
      and stages were earlier than in females, but more had adenoma. The detection rate
      for cancer was 0.18% and the PPV for cancer and all adenomas was 41.3%.
      CONCLUSIONS: The algorithm and FIT following a weak positive gFOBT have
      advantages. FIT following an untestable gFOBT warrants review.

PMID- 22156145
TI  - The D1152H cystic fibrosis mutation in prenatal carrier screening, patients and
      prenatal diagnosis.
AB  - OBJECTIVE: To assess the frequency of the D1152H mutation in the CFTR gene in
      normal individuals, in cystic fibrosis (CF) patients and in the setting of
      prenatal diagnosis. SETTING: A database analysis of sequential screening results
      seen at the Sheba Medical Center, Israel, between 2001 and 2010. METHODS: We
      retrospectively analyzed the frequency of D1152H in a large cohort of healthy
      individuals who were screened as part of a routine prenatal care programme, in
      individuals referred due to CF-related symptoms and in the setting of prenatal
      diagnosis. RESULTS: We found one asymptomatic homozygous female and 195 D1152H
      carriers among 49,940 healthy individuals screened, establishing a carrier rate
      of 1:255 for this mutation. We detected D1152H in nine of 103 individuals
      referred due to CF-related symptoms. Four suffered from respiratory symptoms and
      five from congenital bilateral absence of the vas deferens (CBAVD). During this
      period D1152H was detected in three pregnancies, two of which were aborted.
      CONCLUSION: The increased frequency of D1152H in individuals referred due to CF
      related symptoms compared with healthy individuals included in the CF carrier
      screening programme (P < 0.001) clearly indicates that it is a disease-causing
      mutation.

PMID- 22156146
TI  - Impact of media reporting of cervical cancer in a UK celebrity on a population
      based cervical screening programme.
AB  - OBJECTIVES: To determine the impact of media reporting of cervical cancer in a UK
      celebrity on cervical screening uptake, response time and colposcopy referral and
      attendance. SETTING: Population-based national cervical screening programme for
      women in Wales, UK. METHODS: A time series regression analysis of the Welsh
      national cervical screening and colposcopy databases was used to examine the
      number of smear tests carried out between 2000 and 2010, stratified by age group
      and deprivation indicators. Logistic regression was used to analyse colposcopy
      attendance. RESULTS: Over 33,000 more cervical screening tests than expected were
      carried out in the year of media reporting (2008/9), 11,539 (35%) of which were
      in the month of Jade Goody's death. The largest increase was evident in women
      aged 35-39 years (475 additional tests per month, 95% CI 331-619). Impacts were
      similar across deprivation quintiles. Colposcopy referrals increased by 18%
      during the year of media reporting. Increases were observed for all smear test
      results in 2008/9, particularly among younger women, and further rises were
      evident in 2009/10 for smear tests showing borderline changes and mild
      dyskaryosis. The proportion of women attending colposcopy appointments rose in
      the year of media reporting (chi(2) = 45.8, P < 0.001). CONCLUSIONS: Mass media
      reporting of cervical cancer in a UK celebrity was associated with a significant,
      but transient, increase in screening uptake and colposcopy referral and
      attendance. Mass media reporting can play a role in enhanced detection of
      abnormalities, but public health messages must be communicated effectively to
      minimize anxiety whilst maximizing case-finding and uptake among non-responders.

PMID- 22156147
TI  - Coexistence of t(12;21)(p13;q22)/ETV6-RUNX1 and 11q23/MLL Rearrangement in B
      Acute Lymphoblastic Leukemia: A Case Report and Review of the Literature.

PMID- 22156148
TI  - Real-time prompt gamma monitoring in spot-scanning proton therapy using imaging
      through a knife-edge-shaped slit.
AB  - In this paper we report on Monte Carlo simulations to investigate real-time
      monitoring of the track depth profile in particle therapy by measuring prompt
      gamma ray emissions: a high sensitivity imaging system employing a knife-edge
      shaped slit combined with a position-sensitive gamma detector was evaluated.
      Calculations to test this new concept were performed for a head-sized software
      phantom. Clear spatial correlation is shown between the distribution of gamma
      rays detected with energies above 1.5 MeV and the distribution of prompt gamma
      rays emitted from the phantom. The number of neutrons originating from nuclear
      reactions in the phantom that are detected at these high energies is small. Most
      importantly it is shown that under common therapy conditions enough data may be
      collected during one spot-step (of the order of 10 ms) to locate the distal dose
      edge with a 1sigma accuracy of better than 1 mm. This indicates that simple slit
      cameras have high potential for accurate real-time particle therapy adjustment
      and may become a practical way to improve particle therapy accuracy.

PMID- 22156149
TI  - Vertically ordered magnetic EuTe quantum dots stacks on SnTe matrices.
AB  - Stacked EuTe magnetic quantum dots (QDs) separated by SnTe spacers of increasing
      thickness were grown and studied using x-ray diffraction (XRD) and electron
      microscopy. Grazing incidence XRD indicated that the EuTe QDs are under
      compressive in-plane strain. Both XRD analysis and microscopy images demonstrated
      that the EuTe QDs are vertically aligned, as a result of the strain field
      produced by buried QDs. The width of the lateral error distribution in the QDs'
      vertical alignment from layer to layer decreases for thinner SnTe spacers,
      corresponding to more stressed SnTe matrices. The system can be, therefore, tuned
      to explore magnetic interactions between QDs. The results are discussed in the
      light of previous elastic strain models in anisotropic matrices from the
      literature.

PMID- 22156150
TI  - Routine venography following transaxillary first rib resection and scalenectomy
      (FRRS) for chronic subclavian vein thrombosis ensures excellent outcomes and vein
      patency.
AB  - To assess the role of postoperative venography in patients treated with first rib
      resection and scalenectomy (FRRS) for effort thrombosis, a retrospective review
      was done to evaluate long-term venous patency in 84 patients treated at the Johns
      Hopkins Medical Institutions. Patients undergo venography 2 weeks
      postoperatively. If there is >50% stenosis, the subclavian vein is dilated and
      the patient receives anticoagulation. If the vein is occluded, patients are
      maintained on anticoagulation. Of the 85 patients, 21 patients had patent veins,
      47 patients had stenotic veins, and 16 patients had chronically occluded veins.
      In follow-up, symptomatic restenosis was seen in 3 patients and those veins were
      redilated. Two other patients had late occlusions at 23 and 63 months and
      received anticoagulation and redilatation, respectively. Using venography to
      guide postoperative management, 79 of 84 patients had patent veins many years
      postoperatively. Long-term patency, as seen by duplex scan, was achieved in
      nearly all patients using this protocol.

PMID- 22156151
TI  - Repositioning of surgically placed peritoneovenous shunt catheter by forming "in
      situ" loop snare: case report and review of literature.
AB  - We describe a technique that allows repositioning of malfunctioning
      peritoneovenous shunt (PVS) catheters. We report a 67-year-old female with
      refractory ascites, who presented with malfunctioning PVS. The catheter tip was
      outside the superior vena cava (SVC), possibly in a small mediastinal vein, which
      makes its tip inaccessible to regular snares and retrieval devices. We used "in
      situ" loop snare technique to reposition the tip of the catheter into the
      inferior vena cava (IVC). In situ loop snare technique can be used to reposition
      malfunctioning PVS catheters caused by a kink or by malposition of its tip. The
      technique avoids surgical or interventional replacement of these catheters. This
      technique can be also used for retrieval of foreign body fragments that have no
      free ends and, therefore, cannot be captured by a snare or other retrieval
      devices.

PMID- 22156152
TI  - p53 gene therapy modulates signal transduction in the apoptotic and cell cycle
      pathways downregulating neointimal hyperplasia.
AB  - PURPOSE: To investigate the molecular mechanisms that lead to inhibition of
      intimal hyperplasia (IH) following p53 gene therapy. METHODS: In vivo p53 gene
      transfer to balloon injured rat carotid arteries was performed by utilizing
      adenovirus. The relationship between p53, p21, retinoblastoma protein (Rb), B
      cell lymphoma 2 (Bcl-2), Bax, and Bcl-x was examined by immunohistochemistry.
      Expression of cyclin D1, Fas/CD95, and poly(ADP-ribose)polymerase (PARP) was
      determined. RESULTS: Our data indicate increased expression of p53 in the nuclei
      of vascular smooth muscle cells (VSMCs) in the media (P < .01) compared with the
      controls. In the treated animals, Bax and Bcl-x, p21, and Rb were significantly
      upregulated (P < .01). Immunoreactivity to Bcl-2 was observed only in the
      neointima of untreated groups at 14 days. An increased presence of Fas and
      decreased expression of PARP was observed in the cytoplasm of the VSMCs of p53
      treated animals. CONCLUSIONS: P53 gene transfer activated a battery of downstream
      effector genes whose products are directly involved in cell cycle arrest, DNA
      repair, and apoptosis.

PMID- 22156153
TI  - Fenestrated endograft repair of suprarenal aortic patch aneurysm in a patient
      with Marfan syndrome.
AB  - We present a case of a 4-fenestrated endograft repair of a suprarenal aortic
      patch aneurysm as useful alternative for complex open reoperation in a patient
      with Marfan syndrome.

PMID- 22156154
TI  - The diagnosis and endovascular management of superior mesenteric artery (SMA)
      branch pseudoaneurysms after appendicectomy.
AB  - Pseudoaneurysms arising from the visceral arteries are rare. We present 2
      patients who developed pseudoaneurysms arising from branches of the superior
      mesenteric artery (SMA) following laparoscopic appendicectomy. Both cases were
      successfully treated by endovascular embolization. The diagnosis and management
      of SMA branch pseudoaneurysms are discussed.

PMID- 22156155
TI  - Review of indications and practices of vena caval filters at a large university
      hospital.
AB  - BACKGROUND: Vena caval filter (VCF) use has been increasing in recent years.
      Prophylactic VCF placement has been applied liberally in high-risk patients.
      METHODS: Consecutive patients with VCF placement over a 2-year period at a
      university hospital were reviewed. RESULTS: A total of 244 patients underwent VCF
      placement in 2 years. Of all, 54% of the patients had the VCF placed for an
      absolute indication, 14% for a relative indication, and 32% for prophylaxis. Only
      14 (9%) of the retrievable filters were removed. Eight patients had a
      complication of VCF placement; there were no complications of filter retrieval.
      Vena caval filter placement for prophylaxis alone was 57% from the division of
      trauma and surgical critical care, 18.3% from interventional radiology
      department, and 5.2% from the division of vascular surgery. CONCLUSIONS: This
      study indicates that many VCFs are placed for prophylaxis. A low percentage of
      VCFs was retrieved. This may be the practice at many other large university-based
      hospitals, necessitating strategies for reducing their placement.

PMID- 22156156
TI  - Cerebral intolerance during flow arrested carotid angioplasty.
AB  - INTRODUCTION: The use of flow arrest as a means of providing cerebral protection
      during carotid angioplasty offers the advantages of improved efficiency of debris
      removal and the ability to provide protection under unfavorable (tortuous)
      anatomic circumstances. However, in contrast to the filtration methods of
      cerebral protection, this modality requires complete interruption of antegrade
      carotid artery flow during balloon angioplasty and stent deployment. METHODS: We
      report our experience with 9 patients undergoing carotid angioplasty with the
      Mo.Ma device, which utilizes common and external carotid artery balloon occlusion
      during the angioplasty procedure. We assessed the clinical outcomes and
      intraprocedural hemodynamic data. RESULTS: The average duration of carotid
      occlusion was 8.3 minutes. Of the 9 patients, 2 patients (22%) experienced
      cerebral intolerance. No stroke occurred in this patient cohort. There appeared
      to be a poor relationship between procedure intolerance and the presence of
      significant contralateral stenosis or low carotid back pressure. Furthermore, the
      incidence of postangioplasty hypotension was not clearly related to cerebral
      intolerance. CONCLUSION: Carotid angioplasty with stenting can be safely
      conducted with flow arrest as an alternative to filter-type cerebral protection
      devices. However, because cerebral intolerance is not an infrequent occurrence
      with this approach, clinicians must be cognizant of management strategies for
      transient cerebral intolerance.

PMID- 22156157
TI  - Results of radiofrequency ablation of the small saphenous vein in the supine
      position.
AB  - OBJECTIVES: To report the results of a novel approach using supine positioning
      for radiofrequency ablation (RFA) of the small saphenous vein (SSV) with combined
      ablation of the great saphenous vein (GSV). METHODS: Over a 24-month period, we
      identified patients with symptomatic SSV incompetence. Access to the SSV was
      accomplished by ultrasound-guided venipuncture with the patient in the supine
      position. RESULTS: Small saphenous vein ablation was performed on 27 limbs in 26
      patients. Median follow-up was 94 days (interquartile range [IQR] 26, 171). Mean
      clinical-etiologic-anatomic-pathophysiologic (CEAP) score was 3.5 +/- 1.3. Small
      saphenous vein ablation was performed in conjunction with GSV ablation in 17
      patients and with phlebectomy in 14 patients. Postoperative ultrasound was
      performed after 26 of 27 procedures. The SSV was sealed in all 26 cases. Two
      patients (8%) had a deep venous thrombosis (DVT). CONCLUSIONS: The SSV can be
      effectively sealed by RFA from the supine position and combined SSV/GSV ablation
      can be carried out in a single setting.

PMID- 22156158
TI  - Superior mesenteric vein aneurysm: a case report.
AB  - A 46-year-old female was found to have a saccular superior mesenteric vein (SMV)
      aneurysm on computed tomography (CT) scan during workup for abdominal pain. It
      measured 3.5 cm in diameter. The SMV aneurysm was successfully resected, and the
      SMV was repaired with femoral vein patch angioplasty. She was placed on coumadin
      for 3 months. At follow-up, the vein patch repair was patent and the patient was
      doing well with complete resolution of her abdominal pain.

PMID- 22156159
TI  - Caval agenesis with a hypoplastic left kidney in a patient with trauma on
      warfarin for deep vein thrombosis.
AB  - Congenital anomalies of the inferior vena cava (IVC) are rare, but recognized,
      causing deep venous thrombosis. We present a case of a 50-year-old patient with
      trauma who suffered an intracranial hemorrhage secondary to a fall while on
      anticoagulation for deep vein thromboses. Venous return from the lower
      extremities was determined to be through dilated lumbar venous collaterals into
      the azygous and hemiazygous systems. A second interesting anatomic finding was a
      hypoplastic left kidney.

PMID- 22156160
TI  - Successful extra-anatomical recanalization of occluded superficial femoral
      arteries using the Outback device--a report of 2 cases.
AB  - INTRODUCTION: We report 2 cases where the Outback catheter facilitated extra
      anatomical bypass after vessel perforation during attempted subintimal vessel
      dissection. REPORT: Attempted subintimal angioplasty of the superficial femoral
      artery (SFA) resulted in vessel perforation in 2 patients with chronic SFA
      occlusion and limb ischemia. Due to the lack of other endovascular or surgical
      options, the Outback catheter was used to reenter the patent lumen distal to the
      perforation. A stent graft was then deployed from proximal to the perforation to
      beyond the reentry point with successful outcomes. DISCUSSION: Although the
      reentry devices are typically used to enter the lumen from the subintimal plane,
      this novel technique involves using the Outback catheter to enter from the
      extravascular compartment and facilitate bypass of the SFA occlusion via an extra
      anatomical route. This novel technique can be used to restore in-line blood flow
      when attempted endovascular revascularization failed due to vessel perforation.

PMID- 22156161
TI  - Occlusion of the internal iliac artery prior EVAR: comparison of coils and plugs.
AB  - PURPOSE: We compared occlusion of the internal iliac artery (IIA) using coils or
      the Amplatzer vascular plug (AVP) II prior to endovascular aortic aneurysm
      repair. MATERIALS AND METHODS: Occlusion of the IIA was performed in 32 patients
      (aged 74 +/- 8 years) using coils (N = 17) or the AVP II (N = 15). We
      retrospectively compared procedural data, initial success, and clinical outcome
      in a 12-month follow-up. RESULTS: Occlusion was successful in all patients
      without detection of an endoleak after 12 months. Procedure time and fluoroscopy
      time for coils versus plugs were 77 +/- 35 versus 43 +/- 13 minutes and 36 +/- 19
      versus 18 +/- 8 minutes, respectively (P < .003). Incidence of initial buttock
      claudication (BC) for coils versus plugs was 47% versus 27% and was significantly
      more severe after coil occlusion (P = .03). After a 12-month follow-up, 2
      patients of each group reported of mild BC. CONCLUSION: Occlusion of the IIA is
      safe and effective using coils or plugs. Initial BC is significantly more severe
      when coils are used, but after a 12-month follow-up, there is no significant
      difference. Using a plug is associated with a significant reduction of procedure
      time and radiation exposure.

PMID- 22156162
TI  - RSAT peak-motifs: motif analysis in full-size ChIP-seq datasets.
AB  - ChIP-seq is increasingly used to characterize transcription factor binding and
      chromatin marks at a genomic scale. Various tools are now available to extract
      binding motifs from peak data sets. However, most approaches are only available
      as command-line programs, or via a website but with size restrictions. We present
      peak-motifs, a computational pipeline that discovers motifs in peak sequences,
      compares them with databases, exports putative binding sites for visualization in
      the UCSC genome browser and generates an extensive report suited for both naive
      and expert users. It relies on time- and memory-efficient algorithms enabling the
      treatment of several thousand peaks within minutes. Regarding time efficiency,
      peak-motifs outperforms all comparable tools by several orders of magnitude. We
      demonstrate its accuracy by analyzing data sets ranging from 4000 to 1,28,000
      peaks for 12 embryonic stem cell-specific transcription factors. In all cases,
      the program finds the expected motifs and returns additional motifs potentially
      bound by cofactors. We further apply peak-motifs to discover tissue-specific
      motifs in peak collections for the p300 transcriptional co-activator. To our
      knowledge, peak-motifs is the only tool that performs a complete motif analysis
      and offers a user-friendly web interface without any restriction on sequence size
      or number of peaks.

PMID- 22156163
TI  - Translation of partially overlapping psbD-psbC mRNAs in chloroplasts: the role of
      5'-processing and translational coupling.
AB  - The chloroplast psbD and psbC genes encode the D2 and CP43 proteins of the
      photosystem II complex, and they are generally cotranscribed. We report studies
      on the basic translation process of tobacco psbD-psbC mRNAs using an in vitro
      translation system from tobacco chloroplasts. The primary transcript has an
      unusually long 5'-UTR (905 nt). We show that it is translatable. Processing of
      the 5'-UTR greatly enhances the translation efficiency of the psbD cistron. A
      striking feature is that psbD and psbC cistrons overlap by 14 nt. Removal of the
      psbD 5'-UTR plus the start codon and introduction of a premature termination
      codon in the psbD cistron considerably reduce the translation efficiency of the
      downstream psbC cistron. These results indicate that translation of the psbC
      cistron depends largely on that of the upstream psbD cistron and thus shows
      translational coupling; however, a portion is independently translated. These
      observations, together with the presence of monocistronic psbC mRNAs, suggest
      that the psbD and psbC cistrons are translated via multiple processes to produce
      necessary amounts of D2 and CP43 proteins.

PMID- 22156164
TI  - Predicting the strength of UP-elements and full-length E. coli sigmaE promoters.
AB  - Predicting the location and strength of promoters from genomic sequence requires
      accurate sequenced-based promoter models. We present the first model of a full
      length bacterial promoter, encompassing both upstream sequences (UP-elements) and
      core promoter modules, based on a set of 60 promoters dependent on sigma(E), an
      alternative ECF-type sigma factor. UP-element contribution, best described by the
      length and frequency of A- and T-tracts, in combination with a PWM-based core
      promoter model, accurately predicted promoter strength both in vivo and in vitro.
      This model also distinguished active from weak/inactive promoters. Systematic
      examination of promoter strength as a function of RNA polymerase (RNAP)
      concentration revealed that UP-element contribution varied with RNAP availability
      and that the sigma(E) regulon is comprised of two promoter types, one of which is
      active only at high concentrations of RNAP. Distinct promoter types may be a
      general mechanism for increasing the regulatory capacity of the ECF group of
      alternative sigma's. Our findings provide important insights into the sequence
      requirements for the strength and function of full-length promoters and establish
      guidelines for promoter prediction and for forward engineering promoters of
      specific strengths.

PMID- 22156165
TI  - Protein-mediated protection as the predominant mechanism for defining processed
      mRNA termini in land plant chloroplasts.
AB  - Most chloroplast mRNAs are processed from larger precursors. Several mechanisms
      have been proposed to mediate these processing events, including site-specific
      cleavage and the stalling of exonucleases by RNA structures. A protein barrier
      mechanism was proposed based on analysis of the pentatricopeptide repeat (PPR)
      protein PPR10: PPR10 binds two intercistronic regions and impedes 5'- and 3'
      exonucleases, resulting in processed RNAs with PPR10 bound at the 5'- or 3'-end.
      In this study, we provide evidence that protein barriers are the predominant
      means for defining processed mRNA termini in chloroplasts. First, we map
      additional RNA termini whose arrangement suggests biogenesis via a PPR10-like
      mechanism. Second, we show that the PPR protein HCF152 binds to the immediate 5'-
      or 3'-termini of transcripts that require HCF152 for their accumulation,
      providing evidence that HCF152 defines RNA termini by blocking exonucleases.
      Finally, we build on the observation that the PPR10 and HCF152 binding sites
      accumulate as small chloroplast RNAs to infer binding sites of other PPR
      proteins. We show that most processed mRNA termini are represented by small RNAs
      whose sequences are highly conserved. We suggest that each such small RNA is the
      footprint of a PPR-like protein that protects the adjacent RNA from degradation.

PMID- 22156166
TI  - Validation of an automatic system (DoubleCage) for detecting the location of
      animals during preference tests.
AB  - Preference tests have often been performed for collecting information about
      animals' acceptance of environmental refinement objects. In numerous published
      studies animals were individually tested during preference experiments, as it is
      difficult to observe group-housed animals with an automatic system. Thus,
      videotaping is still the most favoured method for observing preferences of
      socially-housed animals. To reduce the observation workload and to be able to
      carry out preference testing of socially-housed animals, an automatic recording
      system (DoubleCage) was developed for determining the location of group-housed
      animals in a preference test set-up. This system is able to distinguish the
      transition of individual animals between two cages and to record up to 16 animals
      at the same time (four animals per cage). The present study evaluated the
      reliability of the DoubleCage system. The data recorded by the DoubleCage program
      and the data obtained by human observation were compared. The measurements of the
      DoubleCage system and manual observation of the videotapes are comparable and
      significantly correlated (P < 0.0001) with good agreement. Using the DoubleCage
      system enables precise and reliable recording of the preferences of group-housed
      animals and a considerable reduction of animal observation time.

PMID- 22156167
TI  - Anomalous photon-assisted tunneling in  graphene.
AB  - We investigated the transmission of Dirac electrons through a potential barrier
      in the presence of circularly polarized light. An anomalous photon-assisted
      enhanced transmission is predicted and explained. It is demonstrated that the
      perfect transmission for nearly head-on collision in infinite graphene is
      suppressed in gapped dressed states of electrons, which is further accompanied by
      a shift of peaks as a function of the incident angle away from head-on collision.
      In addition, the perfect transmission is partially suppressed by a photon-induced
      gap in illuminated graphene. After the effect of rough edges of the potential
      barrier or impurity scattering is included, the perfect transmission with no
      potential barrier becomes completely suppressed and the energy range for the
      photon-assisted transmission is reduced at the same time.

PMID- 22156168
TI  - Density and size control of InP/GaInP quantum dots on GaAs substrate grown by gas
      source molecular beam epitaxy.
AB  - We demonstrate a method to controllably reduce the density of self-assembled InP
      quantum dots (QDs) by cyclic deposition with growth interruptions. Varying the
      number of cycles enabled a reduction of the QD density from 7.4 * 10(10) cm(-2)
      to 1.8 * 10(9) cm(-2) for the same total amount of deposited InP. Simultaneously,
      a systematic increase of the QD size could be observed. Emission characteristics
      of different-sized InP QDs were analyzed. Excitation power dependent and time
      resolved measurements confirm a transition from type I to type II band alignment
      for large InP quantum dots. Photon autocorrelation measurements of type I QDs
      performed under pulsed excitation reveal pronounced antibunching (g((2))(tau = 0)
      = 0.06 +/- 0.03) as expected for a single-photon emitter. The described growth
      routine has great promise for the exploitation of InP QDs as quantum emitters.

PMID- 22156169
TI  - Does double-row rotator cuff repair improve functional outcome of patients
      compared with single-row technique? A systematic review.
AB  - BACKGROUND: The advantage of single-row versus double-row arthroscopic rotator
      cuff repair techniques has been a controversial issue in sports medicine and
      shoulder surgery. There is biomechanical evidence that double-row techniques are
      superior to single-row techniques; however, there is no clinical evidence that
      the double-row technique provides an improved functional outcome. HYPOTHESIS:
      When compared with single-row rotator cuff repair, double-row fixation, although
      biomechanically superior, has no clinical benefit with respect to retear rate or
      improved functional outcome. STUDY DESIGN: Systematic review. METHODS: The
      authors reviewed prospective studies of level I or II clinical evidence that
      compared the efficacy of single- and double-row rotator cuff repairs. Functional
      outcome scores included the American Shoulder and Elbow Surgeons (ASES) shoulder
      scale, the Constant shoulder score, and the University of California, Los Angeles
      (UCLA) shoulder rating scale. Radiographic failures and complications were also
      analyzed. A test of heterogeneity for patient demographics was also performed to
      determine if there were differences in the patient profiles across the included
      studies. RESULTS: Seven studies fulfilled our inclusion criteria. The test of
      heterogeneity across these studies showed no differences. The functional ASES,
      Constant, and UCLA outcome scores revealed no difference between single- and
      double-row rotator cuff repairs. The total retear rate, which included both
      complete and partial retears, was 43.1% for the single-row repair and 27.2% for
      the double-row repair (P = .057), representing a trend toward higher failures in
      the single-row group. CONCLUSION: Through a comprehensive literature search and
      meta-analysis of current arthroscopic rotator cuff repairs, we found that the
      single-row repairs did not differ from the double-row repairs in functional
      outcome scores. The double-row repairs revealed a trend toward a lower
      radiographic proven retear rate, although the data did not reach statistical
      significance. There may be a concerning trend toward higher retear rates in
      patients undergoing a single-row repair, but further studies are required.

PMID- 22156170
TI  - Physical examination of the athlete's elbow.
AB  - Elbow injury is encountered less frequently than are other joint conditions. The
      bony architecture, muscle, ligament, and nerve anatomy are complex, and the
      forces leading to injury in the athlete's elbow are unique. Appreciating the
      pathomechanics leading to injury and a detailed knowledge of elbow anatomy are
      the foundation for conducting a directed history and physical examination that
      achieves an accurate diagnosis. Recent advances in physical examination have
      improved our ability to accurately diagnose and treat athletic elbow disorders.
      This article reviews general and focused physical examination maneuvers of the
      elbow in a systematic anatomic fashion.

PMID- 22156171
TI  - Effectiveness of the women's lacrosse protective eyewear mandate in the reduction
      of eye injuries.
AB  - BACKGROUND: In an effort to minimize the risk of catastrophic eye injury, US
      Lacrosse initiated mandatory use of protective eyewear in women's lacrosse in the
      2004-2005 season. PURPOSE: The authors compared eye injury rates in girls'
      scholastic lacrosse before and after implementation of protective eyewear. They
      also compared head/face injury rates, concussion rates, and overall injury rates
      before and after the rule change to assess possible unintended consequences of
      the change. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The study
      group included female scholastic lacrosse players in the 25 public high schools
      in Fairfax County, Virginia, during the 2004-2009 spring seasons. Injury rates
      were compared with those from the same data source for the 2000-2003 seasons.
      Premandate versus postmandate injury rates were adjusted for athlete exposures,
      or total opportunities for injury throughout the season. RESULTS: The rate of eye
      injuries was reduced from 0.10 injuries per 1000 athlete exposures (AEs) in 2000
      through 2003 before the use of protective eyewear to 0.016 injuries per 1000 AEs
      in 2004 through 2009 (incident rate ratio [IRR], 0.16; 95% confidence interval
      [CI], 0.06-0.42). The rate ratio of head/face injuries excluding concussion also
      decreased (IRR, 0.44; 95% CI, 0.26-0.76). There was no change in the rate ratio
      of total injuries involving all body parts (IRR, 0.93; 95% CI, 0.82-1.1) after
      introduction of protective eyewear. However, the rate ratio of concussion
      increased (IRR, 1.6; 95% CI, 1.1-2.3). CONCLUSION: The use of protective eyewear
      in women's lacrosse was associated with a reduction in the number of eye
      injuries. The number of head/face injuries decreased in this study group after
      introduction of protective eyewear, and there was no change in overall injury
      rates. The reason for the increase in concussion rate cannot be determined
      conclusively based on this study, but the authors speculate that this increase
      resulted largely from increased recognition and diagnosis because overall injury
      rates do not indicate rougher play with introduction of protective equipment.

PMID- 22156172
TI  - Sequential resection of the distal clavicle and its effects on horizontal
      acromioclavicular joint translation.
AB  - BACKGROUND: Reconstructions of the coracoclavicular (CC) ligament in an open or
      arthroscopically assisted procedure are often combined with a resection of the
      distal clavicle to prevent or treat osteoarthritic degenerations of the
      acromioclavicular (AC) joint. However, increased horizontal translation leading
      to symptomatic instability may be associated with resection of the distal
      clavicle. HYPOTHESIS: Horizontal translation increases in direct correlation to
      subsequent resection of the distal clavicle. STUDY DESIGN: Controlled laboratory
      study. METHODS: Twelve fresh-frozen specimens (mean age, 82.0 +/- 5 years) were
      examined using a servohydraulic testing system. A 70-N force was applied in the
      anterior, posterior, and superior directions, and the translations were
      quantified for all directions. After native testing, sequential resection of the
      distal clavicle at 5 and 10 mm was performed after incision of the inferior
      capsule, and anterior-posterior loads were retested. Finally, the AC ligaments
      were incised, and repeated testing was performed. RESULTS: Native mean (+/-
      standard deviation) anterior translation was 7.90 +/- 2.62 mm. After section of
      the inferior AC capsule, anterior translation was 8.05 +/- 2.62 mm (P = 1.0).
      After clavicle resection of 5 mm, anterior translation was 10.75 +/- 2.38 mm (P =
      .122), and after resection of 10 mm, anterior translation was significantly
      increased to 11.6 +/- 2.37 mm (P = .012). Complete AC capsule sectioning led to
      significantly greater amounts of anterior translation (12.12 +/- 3.0 mm; P =
      .003). Posterior translation for the native specimen was 8.88 +/- 2.63 mm.
      Sectioning of the inferior AC capsule resulted in 9.21 +/- 2.71-mm translation (P
      = 1.0). After clavicle resection of 5 mm, posterior translation was 10.42 +/-
      2.42 mm (P = 1.0), and after 10-mm resection, it was 11.31 +/- 2.86 mm (P = .39).
      Sectioning of the complete AC capsule led to significantly greater amounts of
      posterior translation (12.31 +/- 3.12 mm; P = .043). CONCLUSION: Ten millimeters
      of resection increased anterior translation of the distal clavicle with both the
      superior and posterior AC capsules as well as the CC ligaments intact. Both
      anterior and posterior translations increased after 10-mm resection and complete
      AC capsule sectioning. CLINICAL RELEVANCE: These results suggest that resection
      of the distal clavicle leads to increased horizontal translation despite an
      intact superior and posterior AC capsule. Only sparing resection of the distal
      clavicle should be performed and only if strictly indicated. Violation of the AC
      capsule further increases horizontal translation and should therefore be avoided,
      or if indicated in AC joint dislocations, a reconstruction of the AC capsule
      should be considered.

PMID- 22156173
TI  - Calcifying tendinitis of the shoulder: midterm results after arthroscopic
      treatment.
AB  - BACKGROUND: Calcifying tendinitis is a common and painful disorder of the
      shoulder characterized by the presence of calcific deposits in the tendons of the
      rotator cuff. When nonoperative treatment over a prolonged period of time fails,
      surgical treatment should be considered. Midterm success rates are inconsistent,
      and the role of subacromial decompression is still unclear. HYPOTHESIS: Our
      hypotheses were that the rate of supraspinatus tears after arthroscopic treatment
      of calcifying tendinitis is comparable with that in the contralateral uninvolved
      shoulder and that subacromial decompression does not have beneficial effects
      compared with calcium removal alone. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: In 70 shoulders of 62 patients with a mean age of 54 years,
      arthroscopic removal of calcium deposits of the supraspinatus tendon was
      performed. In 44 shoulders, additional subacromial decompression was performed.
      After a mean follow-up of 6 years (range, 2-13 years), patients were clinically
      investigated, and function was statistically evaluated using Constant and
      American Shoulder and Elbow Surgeons (ASES) scores. Affected and contralateral
      shoulders were examined by ultrasound in 48 shoulders, and rotator cuff tears
      were documented. RESULTS: The mean Constant scores of the operated shoulders were
      significantly lower than those of the healthy shoulders (P < .001). The ASES
      scores significantly (P < .001) increased after surgery but were still lower than
      the ASES scores of the healthy shoulders (P < .001). Concerning the additional
      subacromial decompression, there were no significant differences in the overall
      ASES and Constant scores; the subitem "pain" was significantly better in the
      subacromial decompression group (P = .048). Ultrasound examination at last follow
      up (48 shoulders) showed a partial supraspinatus tendon tear in 11 operated and 3
      contralateral shoulders. CONCLUSION: Although the good clinical results after
      arthroscopic treatment of calcifying tendinitis of the shoulder persist midterm,
      the affected shoulders present significantly lower clinical scores than healthy
      shoulders. The rate of partial supraspinatus tendon tears seems to be higher
      after calcium removal. Additional subacromial decompression seems to reduce
      postoperative pain.

PMID- 22156174
TI  - Ultra-low dose CT attenuation correction for PET/CT.
AB  - A challenge for positron emission tomography/computed tomography (PET/CT)
      quantitation is patient respiratory motion, which can cause an underestimation of
      lesion activity uptake and an overestimation of lesion volume. Several
      respiratory motion correction methods benefit from longer duration CT scans that
      are phase matched with PET scans. However, even with the currently available,
      lowest dose CT techniques, extended duration cine CT scans impart a substantially
      high radiation dose. This study evaluates methods designed to reduce CT radiation
      dose in PET/CT scanning. We investigated selected combinations of dose reduced
      acquisition and noise suppression methods that take advantage of the reduced
      requirement of CT for PET attenuation correction (AC). These include reducing CT
      tube current, optimizing CT tube voltage, adding filtration, CT sinogram
      smoothing and clipping. We explored the impact of these methods on PET
      quantitation via simulations on different digital phantoms. CT tube current can
      be reduced much lower for AC than that in low dose CT protocols. Spectra that are
      higher energy and narrower are generally more dose efficient with respect to PET
      image quality. Sinogram smoothing could be used to compensate for the increased
      noise and artifacts at radiation dose reduced CT images, which allows for a
      further reduction of CT dose with no penalty for PET image quantitation. When CT
      is not used for diagnostic and anatomical localization purposes, we showed that
      ultra-low dose CT for PET/CT is feasible. The significant dose reduction
      strategies proposed here could enable respiratory motion compensation methods
      that require extended duration CT scans and reduce radiation exposure in general
      for all PET/CT imaging.

PMID- 22156175
TI  - Ileal pouch anal anastomosis: an overview of surgery, recovery, and achieving
      postsurgical continence    .
AB  - Ileal pouch anal anastomosis (IPAA) is a two- or three-stage surgical procedure
      performed to treat patients with ulcerative colitis (UC) or familial adenomatous
      polyposis (FAP). Following ileostomy closure and anastomosis, patient goals of
      care typically include obtaining continence and preventing complications. Nursing
      interventions to achieve these goals may include developing a skin care regimen,
      pelvic muscle floor exercises (PFME), diet changes, medication use and coping
      strategies. Research suggests that patient quality of life following surgery is
      generally good, especially in patients with a functioning pouch or a history of
      severe UC and a functioning pouch. However, the procedure is relatively new, and
      long-term (>20 years) outcomes remain largely unknown. Ongoing assessments to
      monitor complications such as pouchitis and pouch stricture are needed, as is
      research to determine the long-term effects of vaginal delivery and of living
      into the seventh, eighth, and ninth decades of life.

PMID- 22156176
TI  - Negative pressure wound therapy-associated tissue trauma and pain: a controlled
      in vivo study comparing foam and gauze dressing removal by immunohistochemistry
      for substance P and calcitonin gene-related peptide in the wound edge.
AB  - Pain upon negative pressure wound therapy (NPWT) dressing removal has been
      reported and is believed to be associated with the observation that granulation
      tissue grows into foam. Wound tissue damage upon removal of the foam may cause
      the reported pain. Calcitonin gene-related peptide (CGRP) and substance P are
      neuropeptides that cause inflammation and signal pain and are known to be
      released when tissue trauma occurs. The aim of this controlled in vivo study was
      to compare the expression of CGRP and substance P in the wound bed in control
      wounds and following NPWT and foam or gauze dressing removal. Eight pigs with two
      wounds each were treated with open-pore structure polyurethane foam or AMD gauze
      and NPWT of 0 (control) or -80 mm Hg for 72 hours. Following removal of the wound
      filler, the expression of CGRP and substance P was measured, using arbitrary
      units, in sections of biopsies from the wound bed using immunofluorescence
      techniques. Substance P and CGRP were more abundant in the wound edge following
      the removal of foam than of gauze dressings and least abundant in control wounds.
      The immunofluorescence staining of the wound edge for CGRP was 52 +/- 3 au after
      the removal of gauze and 97 +/- 5 au after the removal of foam (P <0.001). For
      substance P, the staining was 55 +/- 3 au after gauze removal and 95 +/- 4 au
      after foam removal (P <0.001). CGRP and substance P staining was primarily
      located to nerves and leukocytes. The increase in CGRP and substance P
      immunofluorescence was especially prominent in the dermis but also was seen in
      subcutaneous and muscle tissue. Using gauze may be one way of reducing NPWT
      dressing change-related pain. New wound fillers designed to optimize granulation
      tissue formation and minimize pain issues presumably will be developed in the
      near future.

PMID- 22156177
TI  - Using a diagnostic tool to identify elevated protease activity levels in chronic
      and stalled wounds: a consensus panel discussion.
AB  - Care of chronic and stalled wounds is hampered by the lack of diagnostic tools
      to help direct clinicians to specific treatments or diagnose specific conditions.
      Studies have shown a correlation between high protease levels and nonhealing
      wounds; a diagnostic protease test is under development. Seven wound care experts
      (two podiatrists, two vascular surgeons, a physician expert in hyperbaric oxygen
      therapy, a physical therapist with a specialty in home health, and a registered
      nurse) met to reach consensus on several aspects about a point-of-care protease
      test. They agreed that although disease states interfere with wound healing, such
      states do not automatically mean that wound healing will be impaired or that the
      wound becomes stalled after inception; and that patient comorbidities, patient
      factors, patient medications, and the microenvironment of the wound all affect
      the risk of nonhealing. They also agreed that: 1) appropriate protease activity
      was important in healing, 2) measuring just one individual protease would be
      unlikely to be representative of the proteolytic environment of the wound, 3) no
      diagnostic or theranostic tests to detect high protease activity levels in a
      wound is currently available, and 4) the development of a simple, widely
      available protease diagnostic test could dramatically change the provision of
      care, especially in outpatient settings. If subsequent research confirms that
      high protease activity levels delay healing, confirmation that a stalled wound
      has high protease activity levels could better target protease-modulating
      therapies and improve outcomes. Extensive validation of a protease test will be
      necessary from proof-of-concept pilot studies to controlled clinical trials to
      demonstrate that use of the test improves outcomes of care.

PMID- 22156178
TI  - Editor-in-chief valedictory.

PMID- 22156179
TI  - WBAs in orthodontic postgraduate education: why and how?

PMID- 22156180
TI  - Bullying in orthodontic patients and its relationship to malocclusion,self-esteem
      and oral health-related quality of life.
AB  - OBJECTIVES: To measure the self-reported frequency and severity of bullying
      amongst patients referred for orthodontic treatment and to investigate whether
      there is a relationship between levels of self-reported bullying, malocclusion
      and need for orthodontic treatment and an individual's self-esteem and oral
      health-related quality of life (OHRQoL). DESIGN AND SETTING: Cross-sectional
      study of an adolescent group referred for orthodontic assessment at three UK
      hospitals. SUBJECTS AND METHODS: Three hundred and thirty-six participants aged
      between 10 and 14 years were recruited. Validated questionnaires were used to
      measure the self-reported frequency and severity of bullying, self-esteem and
      OHRQoL. Orthodontic treatment need was assessed using IOTN. RESULTS: The
      prevalence of bullying was 12.8%. Being bullied was significantly associated with
      Class II Division 1 incisor relationship (P = 0.041),increased overbite (P =
      0.023),increased overjet (P = 0.001)and a high need for orthodontic treatment
      assessed using AC IOTN (P = 0.014).Bullied participants also reported lower
      levels of social competence (P<0.001),athletic competence (P<0.001), physical
      appearance related self-esteem (P<0.001)and general self-esteem (P<0.001). Higher
      levels of oral symptoms (P = 0.032),functional limitations (P<0.001), emotional
      (P<0.001)and social impact (P<0.001) from their oral condition, resulting in a
      negative impact on overall OHRQoL (P<0.001),were also reported. CONCLUSIONS:
      Significant relationships exist between bullying and certain occlusal traits,
      self-esteem and OHRQoL.

PMID- 22156181
TI  - Do patient information leaflets affect patients' expectation of orthodontic
      treatment? A randomized controlled trial.
AB  - AIM: To determine the impact that information leaflets have on patient
      expectations of orthodontic treatment. DESIGN: A prospective, randomized
      controlled study. SETTING: The Orthodontic Department at Queen Mary's Sidcup,
      South London Healthcare NHS Trust. PARTICIPANTS: Eighty adolescents, aged 12-14
      years,attending their first orthodontic consultation appointment. INTERVENTION:
      PARTICIPANTS completed a previously validated questionnaire about their
      expectations of orthodontic before the consultation.They were then randomly
      assigned to two groups. The control group (n = 40)received additional written
      information about fluoride, while the intervention group (n = 40) received
      additional written information about orthodontic treatment. Both groups then had
      their orthodontic consultation following which they completed the expectation
      questionnaire for a second time. OUTCOMES: The questionnaire consisted of 10
      questions.Eight questions used a 10 mm VAS response code. Two questions had
      categorical response codes. ANCOVA was undertaken using post-consultation scores
      as the outcome and pre-consultation scores as the covariant. Chi-squared tests
      were undertaken to assess the categorical variables. RESULTS: All 80 participants
      recruited to the trial completed the questionnaire on two occasions. No
      significant differences between the control group and the intervention in their
      expectations of orthodontic treatment were found, except for one item related to
      the expectation of a discussion about treatment at the initial appointment (P =
      0.04). CONCLUSION: Information leaflets did not have an immediate impact on
      patients' expectations of orthodontic treatment. The cost implication of
      providing information leaflets to patients must be weighed against the limited
      benefit they provide.

PMID- 22156182
TI  - In vitro shearing force testing of two seventh generation self-etching primers.
AB  - OBJECTIVE: The purpose of this study was to evaluate the in vitro shearing force
      performance of orthodontic attachments using two self-etching primers (SEPs):
      iBOND and G-Bond. DESIGN: In vitro, laboratory study. MATERIAL AND METHODS: One
      hundred and eighty human molars were randomly divided into four groups and again
      into three sub-groups with 15 teeth each. Teeth were bonded with a stainless
      steel button (GAC International,Bohemia, NY, USA) using Transbond XT adhesive
      composite. The bonding agents were iBOND, G-Bond, Transbond Plus SEP and
      Transbond XT primer. Shearing force tests were carried out immediately, and at 24
      hours and 3 months using a universal testing machine. Force to debond (N) and
      Adhesive Remnant Index (ARI) scores were evaluated and compared. RESULTS:
      Transbond XT primer required a higher immediate (P<0.05)force to debond when
      compared to the Transbond Plus SEP, iBOND and G-Bond.After 24 hours, mean force
      to debond for Transbond XT primer and Transbond Plus SEP showed significant
      increases. At 3 months, all four bonding agents demonstrated force levels to
      debond that were not significantly different from one another. Furthermore,
      comparison of ARI scores indicated a significant difference between the groups at
      all time points. CONCLUSIONS: iBOND and G-Bond may well sufficiently with stand
      the alignment and occlusal forces imparted by light archwires during immediate
      archwire tie-in and over the initial levelling and alignment phase.

PMID- 22156183
TI  - Impact of wearing fixed orthodontic appliances on oral health-related quality of
      life among Brazilian children.
AB  - OBJECTIVE: To assess the impact of wearing a fixed orthodontic appliance on oral
      health-related quality of life (OHRQoL) among Brazilian children. DESIGN: Cross
      sectional study. SETTING: The Department of Paediatric Dentistry and Orthodontics
      at Federal University of Minas Gerais, Belo Horizonte, Brazil. PARTICIPANTS:
      Sample of 579 children aged 11-14 years. The children were divided into two
      groups: wearing (n = 160)and not wearing (n = 419)a fixed orthodontic appliance.
      METHODS: A clinical examination was performed by a single examiner to determine
      whether or not a fixed orthodontic appliance was worn,the presence of a
      malocclusion using the Dental Aesthetic Index (DAI)and cavitated carious lesions.
      The impact of wearing a fixed orthodontic appliance on OHRQoL was measured using
      the short form of the Brazilian version of the Child Perceptions Questionnaire
      (CPQ(11-14)). Data analysis involved descriptive statistics, Mann-Whitney test
      and univariate/multiple logistic regression. RESULTS: The total CPQ(11-14) score
      revealed a more frequent impact among children who wore a fixed orthodontic
      appliance than those who did not (P = 0.002).Similar findings were observed for
      the FL (P = 0.005),EWB (P = 0.006) and SWB (P = 0.003) subscales.There was no
      statistically significant difference between the two groups regarding the score
      on the OS subscale (P = 0.124).While females were 1.76 times more likely to have
      a worse OHRQoL than males, the use of a fixed orthodontic appliance was also
      significantly associated with a greater chance (OR = 1.60; CI = 1.11-2.33)of
      impacting OHRQoL when both variables were inserted together in the regression
      model. CONCLUSION: Children wearing a fixed orthodontic appliance had
      significantly worse OHRQoL compared with a control group with no malocclusion and
      not wearing a fixed appliance.

PMID- 22156184
TI  - Orthodontic treatment of a transposed gigantic canine --a case report.
AB  - Cuspid gigantism or radicomegaly is a rare occurrence often associated with a
      hereditary, X-linked condition, called oculo-cardio-facio-dental (OFCD)syndrome.
      This syndrome is also characterized by atrial septal defects and/or ventricular
      septal defects, congenital cataracts and unusual facial
      characteristics.Confirmation of this syndrome is often provided by dentists or
      orthodontists when they diagnose an extremely large canine root length from the
      panoramic radiograph. The following case report shows a multidisciplinary
      approach to the dental treatment of a patient with OFCD syndrome and a canine
      first premolar transposition. The orthodontic approach required a mini-plate to
      achieve significant mesial movement of a gigantic maxillary canine that erupted
      in close contact with the first molar.

PMID- 22156185
TI  - Pyogenic granuloma: a rare side complication from an orthodontic appliance.
AB  - This case report discusses a rare side effect associated with the use ofa fixed
      quad helix orthodontic appliance. A 14-year-old healthy girl presented with a
      painful enlarging mass on her tongue, which was causing distress to both her and
      her parents. Investigations confirmed that the mass was a pyogenic granuloma and
      management involved surgical excision of the mass and removal of the quad helix
      appliance. At least once previous case associated with an orthodontic quad helix
      appliance has been reported in the literature.

PMID- 22156189
TI  - Letter to the editor.

PMID- 22156191
TI  - Hard and soft supersymmetry breaking  for 'graphinos' in uniform magnetic fields.
AB  - Using irreducible and reducible representations of the Dirac matrices, we study
      the two- and four-component quantum mechanical supersymmetric (SUSY) theories for
      ultrarelativistic fermions in .2 C 1/ dimensions ('graphinos') in a background
      uniform magnetic field perpendicular to their plane of motion. We then consider
      ordinary and parity-violating mass terms and identify the former as a soft SUSY
      breaking term and the latter as the hard SUSY breaking one.

PMID- 22156192
TI  - Altering the ordering and disordering of a triangular nanographene at room
      temperature.
AB  - Molecular self-organization has the potential to serve as an efficient and
      versatile tool for the spontaneous creation of low-dimensional nanostructures on
      surfaces. We demonstrate how the subtle balance between intermolecular
      interactions and molecule-surface interactions can be altered by modifying the
      environment or through manipulation by means of the tip in a scanning tunnelling
      microscope (STM) at room temperature. We show how this leads to the distinctive
      ordering and disordering of a triangular nanographene molecule, the trizigzag
      hexa-peri-hexabenzocoronenes-phenyl-6 (trizigzagHBC-Ph6), on two different
      surfaces: graphite and Au(111). The assembly of submonolayer films on graphite
      reveals a sixfold packing symmetry under UHV conditions, whereas at the graphite
      phenyloctane interface, they reorganize into a fourfold packing symmetry,
      mediated by the solvent molecules. On Au(111) under UHV conditions in the
      multilayer films we investigated, although disorder prevails with the molecules
      being randomly distributed, their packing behaviour can be altered by the
      scanning motion of the tip. The asymmetric diode-like current-voltage
      characteristics of the molecules are retained when deposited on both substrates.
      This paper highlights the importance of the surrounding medium and any external
      stimulus in influencing the molecular organization process, and offers a unique
      approach for controlling the assembly of molecules at a desired location on a
      substrate.

PMID- 22156193
TI  - A new algorithm for detecting central apnea in neonates.
AB  - Apnea of prematurity is an important and common clinical problem, and is often
      the rate-limiting process in NICU discharge. Accurate detection of episodes of
      clinically important neonatal apnea using existing chest impedance (CI)
      monitoring is a clinical imperative. The technique relies on changes in impedance
      as the lungs fill with air, a high impedance substance. A potential confounder,
      however, is blood coursing through the heart. Thus, the cardiac signal during
      apnea might be mistaken for breathing. We report here a new filter to remove the
      cardiac signal from the CI that employs a novel resampling technique optimally
      suited to remove the heart rate signal, allowing improved apnea detection. We
      also develop an apnea detection method that employs the CI after cardiac
      filtering. The method has been applied to a large database of physiological
      signals, and we prove that, compared to the presently used monitors, the new
      method gives substantial improvement in apnea detection.

PMID- 22156194
TI  - Haptoglobin activates innate immunity to enhance acute transplant rejection in
      mice.
AB  - Immune tolerance to transplanted organs is impaired when the innate immune system
      is activated in response to the tissue necrosis that occurs during harvesting and
      implantation procedures. A key molecule in this immune pathway is the
      intracellular TLR signal adaptor known as myeloid differentiation primary
      response gene 88 (MyD88). After transplantation, MyD88 induces DC maturation as
      well as the production of inflammatory mediators, such as IL-6 and TNF-alpha.
      However, upstream activators of MyD88 function in response to transplantation
      have not been identified. Here, we show that haptoglobin, an acute phase protein,
      is an initiator of this MyD88-dependent inflammatory process in a mouse model of
      skin transplantation. Necrotic lysates from transplanted skin elicited higher
      inflammatory responses in DCs than did nontransplanted lysates, suggesting DC
      mediated responses are triggered by factors released during transplantation.
      Analysis of transplanted lysates identified haptoglobin as one of the proteins
      upregulated during transplantation. Expression of donor haptoglobin enhanced the
      onset of acute skin transplant rejection, whereas haptoglobin-deficient skin
      grafts showed delayed acute rejection and antidonor T cell priming in a MyD88
      dependent graft rejection model. Thus, our results show that haptoglobin release
      following skin necrosis contributes to accelerated transplant rejection, with
      potential implications for the development of localized immunosuppressive
      therapies.

PMID- 22156195
TI  - Alkylpurine-DNA-N-glycosylase confers resistance to temozolomide in xenograft
      models of glioblastoma multiforme and is associated with poor survival in
      patients.
AB  - Glioblastoma multiforme (GBM) is the most common and lethal of all gliomas. The
      current standard of care includes surgery followed by concomitant radiation and
      chemotherapy with the DNA alkylating agent temozolomide (TMZ). O6-methylguanine
      DNA methyltransferase (MGMT) repairs the most cytotoxic of lesions generated by
      TMZ, O6-methylguanine. Methylation of the MGMT promoter in GBM correlates with
      increased therapeutic sensitivity to alkylating agent therapy. However, several
      aspects of TMZ sensitivity are not explained by MGMT promoter methylation. Here,
      we investigated our hypothesis that the base excision repair enzyme alkylpurine
      DNA-N-glycosylase (APNG), which repairs the cytotoxic lesions N3-methyladenine
      and N7-methylguanine, may contribute to TMZ resistance. Silencing of APNG in
      established and primary TMZ-resistant GBM cell lines endogenously expressing MGMT
      and APNG attenuated repair of TMZ-induced DNA damage and enhanced apoptosis.
      Reintroducing expression of APNG in TMZ-sensitive GBM lines conferred resistance
      to TMZ in vitro and in orthotopic xenograft mouse models. In addition, resistance
      was enhanced with coexpression of MGMT. Evaluation of APNG protein levels in
      several clinical datasets demonstrated that in patients, high nuclear APNG
      expression correlated with poorer overall survival compared with patients lacking
      APNG expression. Loss of APNG expression in a subset of patients was also
      associated with increased APNG promoter methylation. Collectively, our data
      demonstrate that APNG contributes to TMZ resistance in GBM and may be useful in
      the diagnosis and treatment of the disease.

PMID- 22156196
TI  - Intra-graft expression of genes involved in iron homeostasis predicts the
      development of operational tolerance in human liver transplantation.
AB  - Following organ transplantation, lifelong immunosuppressive therapy is required
      to prevent the host immune system from destroying the allograft. This can cause
      severe side effects and increased recipient morbidity and mortality. Complete
      cessation of immunosuppressive drugs has been successfully accomplished in
      selected transplant recipients, providing proof of principle that operational
      allograft tolerance is attainable in clinical transplantation. The intra-graft
      molecular pathways associated with successful drug withdrawal, however, are not
      well defined. In this study, we analyzed sequential blood and liver tissue
      samples collected from liver transplant recipients enrolled in a prospective
      multicenter immunosuppressive drug withdrawal clinical trial. Before initiation
      of drug withdrawal, operationally tolerant and non-tolerant recipients differed
      in the intra-graft expression of genes involved in the regulation of iron
      homeostasis. Furthermore, as compared with non-tolerant recipients, operationally
      tolerant patients exhibited higher serum levels of hepcidin and ferritin and
      increased hepatocyte iron deposition. Finally, liver tissue gene expression
      measurements accurately predicted the outcome of immunosuppressive withdrawal in
      an independent set of patients. These results point to a critical role for iron
      metabolism in the regulation of intra-graft alloimmune responses in humans and
      provide a set of biomarkers to conduct drug-weaning trials in liver
      transplantation.

PMID- 22156197
TI  - Coordinate regulation of neutrophil homeostasis by liver X receptors in mice.
AB  - The most abundant immune cell type is the neutrophil, a key first responder after
      pathogen invasion. Neutrophil numbers in the periphery are tightly regulated to
      prevent opportunistic infections and aberrant inflammation. In healthy
      individuals, more than 1 * 109 neutrophils per kilogram body weight are released
      from the bone marrow every 24 hours. To maintain homeostatic levels, an
      equivalent number of senescent cells must be cleared from circulation. Recent
      studies indicate that clearance of senescent neutrophils by resident tissue
      macrophages and DCs helps to set homeostatic levels of neutrophils via effects on
      the IL-23/IL-17/G-CSF cytokine axis, which stimulates neutrophil production in
      the bone marrow. However, the molecular events in phagocytes underlying this
      feedback loop have remained indeterminate. Liver X receptors (LXRs) are members
      of the nuclear receptor superfamily that regulate both lipid metabolic and
      inflammatory gene expression. Here, we demonstrate that LXRs contribute to the
      control of neutrophil homeostasis. Using gain- and loss-of-function models, we
      found that LXR signaling regulated the efficient clearance of senescent
      neutrophils by peripheral tissue APCs in a Mer-dependent manner. Furthermore,
      activation of LXR by engulfed neutrophils directly repressed the IL-23/IL-17/G
      CSF granulopoietic cytokine cascade. These results provide mechanistic insight
      into the molecular events orchestrating neutrophil homeostasis and advance our
      understanding of LXRs as integrators of phagocyte function, lipid metabolism, and
      cytokine gene expression.

PMID- 22156198
TI  - A subset of neutrophils in human systemic inflammation inhibits T cell responses
      through Mac-1.
AB  - Suppression of immune responses is necessary to limit damage to host tissue
      during inflammation, but it can be detrimental in specific immune responses, such
      as sepsis and antitumor immunity. Recently, immature myeloid cells have been
      implicated in the suppression of immune responses in mouse models of cancer,
      infectious disease, bone marrow transplantation, and autoimmune disease. Here, we
      report the identification of a subset of mature human neutrophils
      (CD11cbright/CD62Ldim/CD11bbright/CD16bright) as what we believe to be a unique
      circulating population of myeloid cells, capable of suppressing human T cell
      proliferation. These cells were observed in humans in vivo during acute systemic
      inflammation induced by endotoxin challenge or by severe injury. Local release of
      hydrogen peroxide from the neutrophils into the immunological synapse between the
      neutrophils and T cells mediated the suppression of T cell proliferation and
      required neutrophil expression of the integrin Mac-1 (alphaMbeta2). Our data
      demonstrate that suppression of T cell function can be accomplished by a subset
      of human neutrophils that can be systemically induced in response to acute
      inflammation. Identification of the pivotal role of neutrophil Mac-1 and ROS in
      this process provides a potential target for modulating immune responses in
      humans.

PMID- 22156199
TI  - In vitro modeling of the microvascular occlusion and thrombosis that occur in
      hematologic diseases using microfluidic technology.
AB  - In hematologic diseases, such as sickle cell disease (SCD) and hemolytic uremic
      syndrome (HUS), pathological biophysical interactions among blood cells,
      endothelial cells, and soluble factors lead to microvascular occlusion and
      thrombosis. Here, we report an in vitro "endothelialized" microfluidic
      microvasculature model that recapitulates and integrates this ensemble of
      pathophysiological processes. Under controlled flow conditions, the model enabled
      quantitative investigation of how biophysical alterations in hematologic disease
      collectively lead to microvascular occlusion and thrombosis. Using blood samples
      from patients with SCD, we investigated how the drug hydroxyurea quantitatively
      affects microvascular obstruction in SCD, an unresolved issue pivotal to
      understanding its clinical efficacy in such patients. In addition, we
      demonstrated that our microsystem can function as an in vitro model of HUS and
      showed that shear stress influences microvascular thrombosis/obstruction and the
      efficacy of the drug eptifibatide, which decreases platelet aggregation, in the
      context of HUS. These experiments establish the versatility and clinical
      relevance of our microvasculature-on-a-chip model as a biophysical assay of
      hematologic pathophysiology as well as a drug discovery platform.

PMID- 22156200
TI  - Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in
      treated HIV-infected individuals.
AB  - Depletion of CD4+ T cells from the gut occurs rapidly during acute HIV-1
      infection. This has been linked to systemic inflammation and disease progression
      as a result of translocation of microbial products from the gut lumen into the
      bloodstream. Combined antiretroviral therapy (cART) substantially restores CD4+ T
      cell numbers in peripheral blood, but the gut compartment remains largely
      depleted of such cells for poorly understood reasons. Here, we show that a lack
      of recruitment of CD4+ T cells to the gut could be involved in the incomplete
      mucosal immune reconstitution of cART-treated HIV-infected individuals. We
      investigated the trafficking of CD4+ T cells expressing the gut-homing receptors
      CCR9 and integrin alpha4beta7 and found that many of these T cells remained in
      the circulation rather than repopulating the mucosa of the small intestine. This
      is likely because expression of the CCR9 ligand CCL25 was lower in the small
      intestine of HIV-infected individuals. The defective gut homing of CCR9+beta7+
      CD4+ T cells - a population that we found included most gut-homing Th17 cells,
      which have a critical role in mucosal immune defense - correlated with high
      plasma concentrations of markers of mucosal damage, microbial translocation, and
      systemic T cell activation. Our results thus describe alterations in CD4+ T cell
      homing to the gut that could prevent efficient mucosal immune reconstitution in
      HIV-infected individuals despite effective cART.

PMID- 22156201
TI  - MicroRNA-30e* promotes human glioma cell invasiveness in an orthotopic
      xenotransplantation model by disrupting the NF-kappaB/IkappaBalpha negative
      feedback loop.
AB  - Constitutive activation of NF-kappaB is a frequent event in human cancers,
      playing important roles in cancer development and progression. In nontransformed
      cells, NF-kappaB activation is tightly controlled by IkappaBs. IkappaBs bind NF
      kappaB in the cytoplasm, preventing it from translocating to the nucleus to
      modulate gene expression. Stimuli that activate NF-kappaB signaling trigger
      IkappaB degradation, enabling nuclear translocation of NF-kappaB. Among the genes
      regulated by NF-kappaB are those encoding the IkappaBs, providing a negative
      feedback loop that limits NF-kappaB activity. How transformed cells override this
      NF-kappaB/IkappaB negative feedback loop remains unclear. Here, we report in
      human glioma cell lines that microRNA-30e* (miR-30e*) directly targets the
      IkappaBalpha 3iota-UTR and suppresses IkappaBalpha expression. Overexpression of
      miR-30e* in human glioma cell lines led to hyperactivation of NF-kappaB and
      enhanced expression of NF-kappaB-regulated genes, which promoted glioma cell
      invasiveness in in vitro assays and in an orthotopic xenotransplantation model.
      These effects of miR-30e* were shown to be clinically relevant, as miR-30e* was
      found to be upregulated in primary human glioma cells and correlated with
      malignant progression and poor survival. Hence, miR-30e* provides an epigenetic
      mechanism that disrupts the NF-kappaB/IkappaBalpha loop and may represent a new
      therapeutic target and prognostic marker.

PMID- 22156202
TI  - Defective nuclear IKKalpha function in patients with ectodermal dysplasia with
      immune deficiency.
AB  - Ectodermal dysplasia with immune deficiency (EDI) is an immunological and
      developmental disorder caused by alterations in the gene encoding NF-kappaB
      essential modulator (NEMO; also known as IkappaB kinase gamma subunit
      [IKKgamma]). Missense mutations in the gene encoding NEMO are associated with
      reduced signal-induced nuclear translocation of NF-kappaB proteins, resulting in
      defective expression of NF-kappaB target genes. Here, we report 2 unrelated male
      patients with EDI, both of whom have normal NEMO coding sequences, but exhibit a
      marked reduction in expression of full-length NEMO protein. TLR4 stimulation of
      APCs from these patients induced normal cytoplasmic activation and nuclear
      translocation of NF-kappaB. However, cells deficient in full-length NEMO were
      defective in expression of NF-kappaB-regulated cytokines, such as IL-12,
      suggesting a downstream defect in chromatin accessibility for NF-kappaB
      transcription factors. TLR4-stimulated APCs from the patients were defective in
      IKKalpha-dependent H3 histone phosphorylation at the IL-12 promoter and
      recruitment of NF-kappaB heterodimers RelA and cRel to the promoter. Expression
      of a super-active form of IKKalpha restored IL-12 production in a NEMO knockdown
      human monocytic cell line following LPS treatment. Our findings suggest that NEMO
      regulates the nuclear function of IKKalpha and offer new insights into the
      mechanisms underlying diminished NF-kappaB signaling in patients with EDI.

PMID- 22156203
TI  - Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron
      degeneration, which ultimately leads to paralysis and death. Mutation of TAR DNA
      binding protein 43 (TDP-43) has been linked to the development of an inherited
      form of ALS. Existing TDP-43 transgenic animals develop a limited loss of motor
      neurons and therefore do not faithfully reproduce the core phenotype of ALS.
      Here, we report the creation of multiple lines of transgenic rats in which
      expression of ALS-associated mutant human TDP-43 is restricted to either motor
      neurons or other types of neurons and skeletal muscle and can be switched on and
      off. All of these rats developed progressive paralysis reminiscent of ALS when
      the transgene was switched on. Rats expressing mutant TDP-43 in motor neurons
      alone lost more spinal motor neurons than rats expressing the disease gene in
      varying neurons and muscle cells, although these rats all developed remarkable
      denervation atrophy of skeletal muscles. Intriguingly, progression of the disease
      was halted after transgene expression was switched off; in rats with limited loss
      of motor neurons, we observed a dramatic recovery of motor function, but in rats
      with profound loss of motor neurons, we only observed a moderate recovery of
      motor function. Our finding suggests that mutant TDP-43 in motor neurons is
      sufficient to promote the onset and progression of ALS and that motor neuron
      degeneration is partially reversible, at least in mutant TDP-43 transgenic rats.

PMID- 22156204
TI  - SOX after SOX: SOXession regulates neurogenesis.
AB  - Vertebrate embryonic stem (ES) cells give rise to many different cell types in
      multistep processes. These involve the establishment of a competent state,
      specification, differentiation, and maturation, and often involve Sox
      transcription factors. In this issue of Genes & Development, Bergsland and
      colleagues (pp. 2453-2464) determine the genome-wide binding profile of Sox2,
      Sox3, and Sox11 as ES cells become specified to neural precursors and
      differentiate into neurons. An ordered, sequential binding of these Sox proteins
      to a common set of gene enhancers was found to drive neurogenesis, as Sox
      proteins first help to preselect neural genes in ES cells and later ensure their
      proper activation in neural precursors or neurons.

PMID- 22156205
TI  - Shields up: the Tup1-Cyc8 repressor complex blocks coactivator recruitment.
AB  - The Tup1-Cyc8 complex is responsible for repression of a large and diverse
      collection of genes in Saccharomyces cerevisiae. The predominant view has been
      that Tup1-Cyc8 functions as a corepressor, actively associating with regulatory
      proteins and organizing chromatin to block transcription. A new study by Wong and
      Struhl in this issue of Genes & Development (pp. 2525-2539) challenges nearly 20
      years of models by demonstrating that Tup1-Cyc8 functions primarily as a shield
      to block DNA-binding proteins from recruiting transcriptional coactivators.

PMID- 22156206
TI  - Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation.
AB  - Ten-eleven translocation 1-3 (Tet1-3) proteins have recently been discovered in
      mammalian cells to be members of a family of DNA hydroxylases that possess
      enzymatic activity toward the methyl mark on the 5-position of cytosine (5
      methylcytosine [5mC]), a well-characterized epigenetic modification that has
      essential roles in regulating gene expression and maintaining cellular identity.
      Tet proteins can convert 5mC into 5-hydroxymethylcytosine (5hmC), 5
      formylcytosine (5fC), and 5-carboxylcytosine (5caC) through three consecutive
      oxidation reactions. These modified bases may represent new epigenetic states in
      genomic DNA or intermediates in the process of DNA demethylation. Emerging
      biochemical, genetic, and functional evidence suggests that Tet proteins are
      crucial for diverse biological processes, including zygotic epigenetic
      reprogramming, pluripotent stem cell differentiation, hematopoiesis, and
      development of leukemia. Insights into how Tet proteins contribute to dynamic
      changes in DNA methylation and gene expression will greatly enhance our
      understanding of epigenetic regulation of normal development and human diseases.

PMID- 22156207
TI  - Macrophages and cathepsin proteases blunt chemotherapeutic response in breast
      cancer.
AB  - The microenvironment is known to critically modulate tumor progression, yet its
      role in regulating treatment response is poorly understood. Here we found
      increased macrophage infiltration and cathepsin protease levels in mammary tumors
      following paclitaxel (Taxol) chemotherapy. Cathepsin-expressing macrophages
      protected against Taxol-induced tumor cell death in coculture, an effect fully
      reversed by cathepsin inhibition and mediated partially by cathepsins B and S.
      Macrophages were also found to protect against tumor cell death induced by
      additional chemotherapeutics, specifically etoposide and doxorubicin. Combining
      Taxol with cathepsin inhibition in vivo significantly enhanced efficacy against
      primary and metastatic tumors, supporting the therapeutic relevance of this
      effect. Additionally incorporating continuous low-dose cyclophosphamide
      dramatically impaired tumor growth and metastasis and improved survival. This
      study highlights the importance of integrated targeting of the tumor and its
      microenvironment and implicates macrophages and cathepsins in blunting
      chemotherapeutic response.

PMID- 22156208
TI  - Histone deacetylase 3 is an epigenomic brake in macrophage alternative
      activation.
AB  - Macrophages, a key cellular component of inflammation, become functionally
      polarized in a signal- and context-specific manner. Th2 cytokines such as
      interleukin 4 (IL-4) polarize macrophages to a state of alternative activation
      that limits inflammation and promotes wound healing. Alternative activation is
      mediated by a transcriptional program that is influenced by epigenomic
      modifications, including histone acetylation. Here we report that macrophages
      lacking histone deacetylase 3 (HDAC3) display a polarization phenotype similar to
      IL-4-induced alternative activation and, furthermore, are hyperresponsive to IL-4
      stimulation. Throughout the macrophage genome, HDAC3 deacetylates histone tails
      at regulatory regions, leading to repression of many IL-4-regulated genes
      characteristic of alternative activation. Following exposure to Schistosoma
      mansoni eggs, a model of Th2 cytokine-mediated disease that is limited by
      alternative activation, pulmonary inflammation was ameliorated in mice lacking
      HDAC3 in macrophages. Thus, HDAC3 functions in alternative activation as a brake
      whose release could be of benefit in the treatment of multiple inflammatory
      diseases.

PMID- 22156210
TI  - Nascent-seq indicates widespread cotranscriptional pre-mRNA splicing in
      Drosophila.
AB  - To determine the prevalence of cotranscriptional splicing in Drosophila, we
      sequenced nascent RNA transcripts from Drosophila S2 cells as well as from
      Drosophila heads. Eighty-seven percent of the introns assayed manifest >50%
      cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced
      poorly or slowly, with ~3% being almost completely retained in nascent pre-mRNA.
      Although individual introns showed slight but statistically significant
      differences in splicing efficiency, similar global levels of splicing were seen
      from both sources. Importantly, introns with low cotranscriptional splicing
      efficiencies are present in the same primary transcript with efficiently spliced
      introns, indicating that splicing is intron-specific. The analysis also indicates
      that cotranscriptional splicing is less efficient for first introns, longer
      introns, and introns annotated as alternative. Finally, S2 cells expressing the
      slow RpII215(C4) mutant show substantially less intron retention than wild-type
      S2 cells.

PMID- 22156209
TI  - Restriction of histone gene transcription to S phase by phosphorylation of a
      chromatin boundary protein.
AB  - The cell cycle-regulated expression of core histone genes is required for DNA
      replication and proper cell cycle progression in eukaryotic cells. Although some
      factors involved in histone gene transcription are known, the molecular
      mechanisms that ensure proper induction of histone gene expression during S phase
      remain enigmatic. Here we demonstrate that S-phase transcription of the model
      histone gene HTA1 in yeast is regulated by a novel attach-release mechanism
      involving phosphorylation of the conserved chromatin boundary protein Yta7 by
      both cyclin-dependent kinase 1 (Cdk1) and casein kinase 2 (CK2). Outside S phase,
      integrity of the AAA-ATPase domain is required for Yta7 boundary function, as
      defined by correct positioning of the histone chaperone Rtt106 and the chromatin
      remodeling complex RSC. Conversely, in S phase, Yta7 is hyperphosphorylated,
      causing its release from HTA1 chromatin and productive transcription. Most
      importantly, abrogation of Yta7 phosphorylation results in constitutive
      attachment of Yta7 to HTA1 chromatin, preventing efficient transcription post
      recruitment of RNA polymerase II (RNAPII). Our study identified the chromatin
      boundary protein Yta7 as a key regulator that links S-phase kinases with RNAPII
      function at cell cycle-regulated histone gene promoters.

PMID- 22156211
TI  - Core promoter-selective function of HMGA1 and Mediator in Initiator-dependent
      transcription.
AB  - The factors and mechanisms underlying the differential activity and regulation of
      eukaryotic RNA polymerase II on different types of core promoters have remained
      elusive. Here we show that the architectural factor HMGA1 and the Mediator
      coregulator complex cooperate to enhance basal transcription from core promoters
      containing both a TATA box and an Initiator (INR) element but not from "TATA
      only" core promoters. INR-dependent activation by HMGA1 and Mediator requires the
      TATA-binding protein (TBP)-associated factors (TAFs) within the TFIID complex and
      counteracts negative regulators of TBP/TATA-dependent transcription such as NC2
      and Topoisomerase I. HMGA1 interacts with TFIID and Mediator and is required for
      the synergy of TATA and INR elements in mammalian cells. Accordingly, natural
      HMGA1-activated genes in embryonic stem cells tend to have both TATA and INR
      elements in a synergistic configuration. Our results suggest a core promoter
      specific regulation of Mediator and the basal transcription machinery by HMGA1.

PMID- 22156212
TI  - The Cyc8-Tup1 complex inhibits transcription primarily by masking the activation
      domain of the recruiting protein.
AB  - The yeast Tup1-Cyc8 corepressor complex is recruited to promoters by DNA-binding
      repressors, but the mechanisms by which it inhibits expression of genes involved
      in various stress pathways are poorly understood. Conditional and rapid depletion
      of Tup1 from the nucleus leads to concurrent nucleosome depletion and histone
      acetylation, recruitment of coactivators (Swi/Snf, SAGA, and Mediator), and
      increased transcriptional activity. Conversely, coactivator dissociation occurs
      rapidly upon rerepression by Cyc8-Tup1, although coactivator association and
      transcription can be blocked even in the absence of nucleosomes. The coactivators
      are recruited to the sites where Tup1 was located prior to depletion, indicating
      that the repressor proteins that recruit Tup1 function as activators in its
      absence. Last, Cyc8-Tup1 can interact with activation domains in vivo. Thus, Cyc8
      Tup1 regulates transcription primarily by masking and inhibiting the
      transcriptional activation domains of the recruiting proteins, not by acting as a
      corepressor. We suggest that the corepressor function of Cyc8-Tup1 makes only a
      modest contribution to expression of target genes, specifically to keep
      expression levels below the nonactivated state.

PMID- 22156213
TI  - MicroRNAs as master regulators of the plant NB-LRR defense gene family via the
      production of phased, trans-acting siRNAs.
AB  - Legumes and many nonleguminous plants enter symbiotic interactions with microbes,
      and it is poorly understood how host plants respond to promote beneficial,
      symbiotic microbial interactions while suppressing those that are deleterious or
      pathogenic. Trans-acting siRNAs (tasiRNAs) negatively regulate target transcripts
      and are characterized by siRNAs spaced in 21-nucleotide (nt) "phased" intervals,
      a pattern formed by DICER-LIKE 4 (DCL4) processing. A search for phased siRNAs
      (phasiRNAs) found at least 114 Medicago loci, the majority of which were defense
      related NB-LRR-encoding genes. We identified three highly abundant 22-nt microRNA
      (miRNA) families that target conserved domains in these NB-LRRs and trigger the
      production of trans-acting siRNAs. High levels of small RNAs were matched to >60%
      of all ~540 encoded Medicago NB-LRRs; in the potato, a model for mycorrhizal
      interactions, phasiRNAs were also produced from NB-LRRs. DCL2 and SGS3
      transcripts were also cleaved by these 22-nt miRNAs, generating phasiRNAs,
      suggesting synchronization between silencing and pathogen defense pathways. In
      addition, a new example of apparent "two-hit" phasiRNA processing was identified.
      Our data reveal complex tasiRNA-based regulation of NB-LRRs that potentially
      evolved to facilitate symbiotic interactions and demonstrate miRNAs as master
      regulators of a large gene family via the targeting of highly conserved, protein
      coding motifs, a new paradigm for miRNA function.

PMID- 22156214
TI  - Enhancing nanolithography.

PMID- 22156215
TI  - Central nervous system complications in HIV disease: HIV-associated
      neurocognitive disorder.
AB  - HIV-associated neurocognitive disorder (HAND) is the result of neural damage
      caused by HIV replication and immune activation. Potent antiretroviral therapy
      has reduced the prevalence of severe HAND but not mild to moderate HAND. Brief
      symptom questionnaires, screening tests, and neuropsychological tests can be used
      with relative ease in the clinic to identify cognitive and neurologic deficits
      and to track patient status. Increasing data on pharmacokinetics of
      antiretrovirals in cerebrospinal fluid (CSF) have permitted formulation of
      central nervous system (CNS) penetration-effectiveness (CPE) rankings for single
      drugs and combinations. Available data indicate that regimens with higher CPE
      scores are associated with lower HIV RNA levels in CSF and improvement in
      neurocognitive functioning. This article summarizes a presentation by Scott
      Letendre, MD, at the IAS-USA live continuing medical education course held in San
      Francisco in May 2011.

PMID- 22156216
TI  - Addressing alcohol use in HIV-infected persons.
AB  - Alcohol use is common among persons with HIV infection and is associated with
      worse HIV treatment outcomes. Patients with hazardous levels of use are less
      likely to be receiving antiretroviral therapy, to be adherent to therapy, and to
      achieve virologic suppression. Screening, intervention, and referral to care for
      alcohol use disorder is an integral part of clinical care for individuals with
      HIV infection. Brief screening procedures can identify level of risk and
      determine whether patients require brief alcohol intervention or should be
      considered for behavioral therapy and pharmacologic treatment. Identification of
      concurrent mental health disorders is an important aspect of treating alcohol use
      disorders in HIV infection and other clinical settings. This article summarizes a
      presentation by Geetanjali Chander, MD, MPH, at the 14th Annual Clinical
      Conference for the Ryan White HIV/AIDS Program held in Tampa, Florida, in June
      2011. The Clinical Conference is sponsored by the IAS-USA under the Health
      Resources and Services Administration (HRSA) contract number HHSH250200900010C.

PMID- 22156217
TI  - Safer conception interventions for HIV-affected couples: implications for
      resource-constrained settings.
AB  - Developing and testing safer conception methods that reduce HIV transmission to
      HIV-seronegative partners in serodiscordant couples and reduce superinfection in
      HIV-seroconcordant couples is a crucial but often unaddressed component of HIV
      prevention programs. Most research has focused on developed-world settings, where
      "high-technology" assisted reproduction techniques are used for HIV
      serodiscordant couples in which the male is HIV-infected. There is a dearth of
      research on safer conception methods for HIV-seropositive women and "low
      technology" harm-reduction strategies for HIV-affected couples, including vaginal
      insemination for HIV-seropositive women and natural conception methods for HIV
      seroconcordant and -serodiscordant couples. This review summarizes international
      studies of safer conception interventions for HIV-affected couples, with a focus
      on feasibility in public-sector health settings where assisted reproductive
      technology is not readily available. Given that such low-technology options are
      feasible in most settings, well-designed, prospective interventions offering low
      technology safer conception methods need to be developed and tested.

PMID- 22156219
TI  - Graphene-based one-dimensional  photonic crystal.
AB  - A novel type of one-dimensional (1D) photonic crystal formed by an array of
      periodically located stacks of alternating graphene and dielectric stripes
      embedded into a background dielectric medium is proposed. The wave equation for
      the electromagnetic wave propagating in such a structure is solved in the
      framework of the Kronig-Penney model. The frequency band structure of the 1D
      graphene-based photonic crystal is obtained analytically as a function of the
      filling factor and the thickness of the dielectric between the graphene stripes.
      The photonic frequency corresponding to the electromagnetic wave localized by a
      defect of the photonic crystal formed by an extra dielectric placed in the
      position of one stack of alternating graphene and dielectric stripes is obtained.

PMID- 22156218
TI  - 2011 update of the drug resistance mutations in HIV-1.
AB  - This November 2011 edition of the IAS-USA drug resistance mutations list updates
      the figures last published in December 2010 (Johnson VA et al, Top HIV Med,
      2010;18:156-163).

PMID- 22156220
TI  - Novel tunable hierarchical Ni-Co hydroxide and oxide assembled from two-wheeled
      units.
AB  - A novel hierarchical Ni-Co hydroxide assembled from two-wheeled units was
      successfully synthesized via a simple, hydrothermal method through the reaction
      of nickel salt, cobalt salt and sodium hydroxide, and with a chelating agent
      (EDA) to control the precipitation rate. The as-synthesized materials were
      characterized by x-ray diffraction (XRD), field-emission scanning electron
      microscopy (FESEM), transmission electron microscopy (TEM), high-resolution
      transmission electron microscopy (HRTEM), Fourier transform infrared spectroscopy
      (FTIR), atomic absorption spectrophotometer (AAS) and thermogravimetric analysis
      (TG). The Ni(2+)/Co(2+) molar ratio R in the initial solution plays an important
      role to control the morphology of the hierarchical Ni-Co hydroxide. The influence
      of the EDA concentration, reaction temperature and NaOH concentration on the
      formation of the hierarchical Ni-Co hydroxide was also investigated. The
      formation mechanism of the hierarchical Ni-Co hydroxide assembled by two-wheeled
      units was proposed. A Ni-Co oxide with a similar structure was obtained by
      calcination of the as-prepared Ni-Co hydroxide.

PMID- 22156221
TI  - Determination of blood volume by pulse CO-oximetry.
AB  - The objective of this study was to determine whether changes in
      carboxyhaemoglobin (COHb) saturation following carbon monoxide (CO) rebreathing
      can be accurately detected by pulse CO-oximetry in order to determine blood
      volume. Noninvasive measurements of carboxyhaemoglobin saturation (SpCO) were
      continuously monitored by pulse CO-oximetry before, during and following 2 min of
      CO rebreathing. Reproducibility and accuracy of noninvasive blood volume
      measurements were determined in 16 healthy non-smoking individuals (15 males,
      age: 28 +/- 2 years, body mass index: 25.4 +/- 0.6 kg m(-2)) through comparison
      with blood volume measurements calculated from invasive measurements of COHb
      saturation. The coefficient of variation for noninvasive blood volume
      measurements performed on separate days was 15.1% which decreases to 9.1% when
      measurements were performed on the same day. Changes in COHb saturation and SpCO
      following CO rebreathing were strongly correlated (r = 0.90, p < 0.01), resulting
      in a significant correlation between invasive and noninvasive blood volume
      measurements (r = 0.83, p = 0.02). Changes in SpCO following CO rebreathing can
      be accurately detected by pulse CO-oximetry, which could potentially provide a
      simplified, convenient and reproducible method to rapidly determine blood volume
      in healthy individuals.

PMID- 22156222
TI  - A human islet cell culture system for high-throughput screening.
AB  - A small-molecule inducer of beta-cell proliferation in human islets represents a
      potential regeneration strategy for treating type 1 diabetes. However, the lack
      of suitable human beta cell lines makes such a discovery a challenge. Here, we
      adapted an islet cell culture system to high-throughput screening to identify
      such small molecules. We prepared microtiter plates containing extracellular
      matrix from a human bladder carcinoma cell line. Dissociated human islets were
      seeded onto these plates, cultured for up to 7 days, and assessed for
      proliferation by simultaneous Ki67 and C-peptide immunofluorescence. Importantly,
      this environment preserved beta-cell physiological function, as measured by
      glucose-stimulated insulin secretion. Adenoviral overexpression of cdk-6 and
      cyclin D(1), known inducers of human beta cell proliferation, was used as a
      positive control in our assay. This induction was inhibited by cotreatment with
      rapamycin, an immunosuppressant often used in islet transplantation. We then
      performed a pilot screen of 1280 compounds, observing some phenotypic effects on
      cells. This high-throughput human islet cell culture method can be used to assess
      various aspects of beta-cell biology on a relatively large number of compounds.

PMID- 22156223
TI  - Optimization of fluorescently labeled Nrf2 peptide probes and the development of
      a fluorescence polarization assay for the discovery of inhibitors of Keap1-Nrf2
      interaction.
AB  - Activation of the antioxidant response element (ARE) upregulates enzymes involved
      in detoxification of electrophiles and reactive oxygen species. The induction of
      ARE genes is regulated by the interaction between redox sensor protein Keap1 and
      the transcription factor Nrf2. Fluorescently labeled Nrf2 peptides containing the
      ETGE motif were synthesized and optimized as tracers in the development of a
      fluorescence polarization (FP) assay to identify small-molecule inhibitors of the
      Keap1-Nrf2 interaction. The tracers were optimized to increase the dynamic range
      of the assay and their binding affinities to the Keap1 Kelch domain. The binding
      affinities of Nrf2 peptide inhibitors obtained in our FP assay using FITC-9mer
      Nrf2 peptide amide as the probe were in good agreement with those obtained
      previously by a surface plasmon resonance assay. The FP assay exhibits
      considerable tolerance toward DMSO and produced a Z' factor greater than 0.6 in a
      384-well format. Further optimization of the probe led to cyanine-labeled 9mer
      Nrf2 peptide amide, which can be used along with the FITC-9mer Nrf2 peptide amide
      in a high-throughput screening assay to discover small-molecule inhibitors of
      Keap1-Nrf2 interaction.

PMID- 22156224
TI  - High-throughput fluorescence polarization assay for chemical library screening
      against anti-apoptotic Bcl-2 family member Bfl-1.
AB  - Overexpression of the anti-apoptotic Bcl-2 family proteins occurs commonly in
      human cancers. Bfl-1 is highly expressed in some types of malignant cells,
      contributing significantly to tumor cell survival and chemoresistance. Therefore,
      it would be desirable to have chemical antagonists of Bfl-1. To this end, we
      devised a fluorescence polarization assay (FPA) using Bfl-1 protein and
      fluorescein-conjugated Bid BH3 peptide, which was employed for high-throughput
      screening of chemical libraries. Approximately 66 000 compounds were screened for
      the ability to inhibit BH3 peptide binding to Bfl-1, yielding 14 reproducible
      hits with >=50% displacement. After dose-response analysis and confirmation using
      a secondary assay based on time-resolved fluorescence resonance energy transfer
      (TR-FRET), two groups of Bfl-1-specific inhibitors were identified, including
      chloromaleimide and sulfonylpyrimidine series compounds. FPAs generated for each
      of the six anti-apoptotic Bcl-2 proteins demonstrated selective binding of both
      classes of compounds to Bfl-1. Analogs of the sulfonylpyrimidine series were
      synthesized and compared with the original hit for Bfl-1 binding by both FPAs and
      TR-FRET assays. The resulting structure-activity relation analysis led to the
      chemical probe compound CID-2980973 (ML042). Collectively, these findings
      demonstrate the feasibility of using the HTS assay for discovery of selective
      chemical inhibitors of Bfl-1.

PMID- 22156225
TI  - Development of a high-throughput screening method for LIM kinase 1 using a
      luciferase-based assay of ATP consumption.
AB  - Kinases are attractive drug targets because of the central roles they play in
      signal transduction pathways and human diseases. Their well-formed adenosine
      triphosphate (ATP)-binding pockets make ideal targets for small-molecule
      inhibitors. For drug discovery purposes, many peptide-based kinase assays have
      been developed that measure substrate phosphorylation using fluorescence-based
      readouts. However, for some kinases these assays may not be appropriate. In the
      case of the LIM kinases (LIMK), an inability to phosphorylate peptide substrates
      resulted in previous high-throughput screens (HTS) using radioactive labeling of
      recombinant cofilin protein as the readout. We describe the development of an HTS
      compatible assay that measures relative ATP levels using luciferase-generated
      luminescence as a function of LIMK activity. The assay was inexpensive to
      perform, and proof-of-principle screening of kinase inhibitors demonstrated that
      compound potency against LIMK could be determined; ultimately, the assay was used
      for successful prosecution of automated HTS. Following HTS, the secondary assay
      format was changed to obtain more accurate measures of potency and mechanism of
      action using more complex (and expensive) assays. The luciferase assay
      nonetheless provides an inexpensive and reliable primary assay for HTS that
      allowed for the identification of LIMK inhibitors to initiate discovery programs
      for the eventual treatment of human diseases.

PMID- 22156226
TI  - Molecular spectrum of somaclonal variation in regenerated rice revealed by whole
      genome sequencing.
AB  - Somaclonal variation is a phenomenon that results in the phenotypic variation of
      plants regenerated from cell culture. One of the causes of somaclonal variation
      in rice is the transposition of retrotransposons. However, many aspects of the
      mechanisms that result in somaclonal variation remain undefined. To detect genome
      wide changes in regenerated rice, we analyzed the whole-genome sequences of three
      plants independently regenerated from cultured cells originating from a single
      seed stock. Many single-nucleotide polymorphisms (SNPs) and insertions and
      deletions (indels) were detected in the genomes of the regenerated plants. The
      transposition of only Tos17 among 43 transposons examined was detected in the
      regenerated plants. Therefore, the SNPs and indels contribute to the somaclonal
      variation in regenerated rice in addition to the transposition of Tos17. The
      observed molecular spectrum was similar to that of the spontaneous mutations in
      Arabidopsis thaliana. However, the base change ratio was estimated to be 1.74 *
      10(-6) base substitutions per site per regeneration, which is 248-fold greater
      than the spontaneous mutation rate of A. thaliana.

PMID- 22156227
TI  - Immunohistochemical characteristics of normal canine eyes.
AB  - Immunohistochemistry is widely utilized in diagnostic laboratories to study
      neoplastic and nonneoplastic diseases. Knowledge of the immunohistochemical
      characteristics of normal tissue is essential for interpretation of
      immunoreactivity in pathologic conditions. In this study, immunohistochemistry
      was performed with a broad panel of diagnostically relevant antibodies on 4
      normal canine globes--namely, vimentin, pan-cytokeratin (AE1/AE3), cytokeratin 7,
      cytokeratin 8/18, cytokeratin 20, alpha-smooth muscle actin, muscle specific
      actin, desmin, Melan-A, microphthalmia transcription factor, S-100, glial
      fibrillary acidic protein, triple neurofilaments, neuron-specific enolase,
      chromogranin A, synaptophysin, laminin and CD31. Results include cytokeratin
      immunoreactivity limited to the conjunctival epithelium, corneal epithelium, and
      retinal pigment epithelium; distinct patterns of immunopositivity of muscle
      markers; and widespread immunoreactivity for vimentin and most
      neural/neuroendocrine markers. These findings in normal eyes provide the basis
      for interpretation of ocular immunohistochemistry in dogs. Published
      immunophenotypes of primary ocular neoplasms are also reviewed.

PMID- 22156228
TI  - Spontaneous glomerular and tubulointerstitial lesions in common marmosets
      (Callithrix jacchus).
AB  - Spontaneous progressive nephropathy dominated by glomerular lesions in common
      marmosets has been reported. However, the histopathologic characteristics,
      including the relationship between glomerular and tubulointerstitial lesions,
      have not been described in detail. In the present study, the authors examined the
      histopathologic characteristics of the background renal lesions in common
      marmosets (3 males and 9 females, 3 to 8 years old). The severity of glomerular
      lesions was graded into 3 classes: grade I, no alteration; grade II, hilar/focal
      increase of mesangial matrix; grade III, global/diffuse increase of mesangial
      matrix. Tubulointerstitial lesions (tubular regeneration and hyperplasia and
      interstitial inflammation and fibrosis) were scored according to the area of each
      lesion. The renal lesions were characterized by enlargement of glomeruli,
      expanded mesangial area with increase of periodic acid-Schiff reaction-positive
      matrix, tubular regeneration and hyperplasia, and interstitial inflammation and
      fibrosis. Glomerular lesions progressed with increasing mesangial matrix and
      aging. Additionally, the tubulointerstitial lesions became exacerbated with
      progressing glomerular lesions. Tubular hyperplasia was divided into 4 types
      according to the structure of the cell layer (simple or stratified-like), the
      area of increased lining cells (partial or entire), cytoplasmic staining
      (eosinophilic or basophilic), brush border and thickness of basement membrane,
      and the activity of cell proliferation. In conclusion, the background renal
      lesions in common marmosets were characterized by glomerular lesions with
      increase of mesangial matrix, which progressed with aging, and secondary
      tubulointerstitial lesions, including tubular hyperplasia. Those lesions were
      thus diagnosed as progressive glomerulonephropathy in common marmosets.

PMID- 22156230
TI  - Reporting standards for studies of tailored interventions.
AB  - Message tailoring is a promising innovative approach to persuasive communication
      that involves designing messages to meet a person's psychological, behavioral
      and/or demographic characteristics. Although the tailored intervention literature
      has many strengths, a weakness is inconsistency in reporting information related
      to intervention development, implementation and evaluation. The objective of this
      manuscript is to report recommendations for studies of tailored interventions. As
      part of ongoing original empirical and meta-analytical research, we reviewed the
      tailoring literature and identified inconsistencies in reporting. We compared
      these inconsistencies with existing reporting standards and developed
      recommendations specific to tailored interventions. An advisory board of
      preeminent tailoring researchers provided feedback on draft and final
      recommendations. This paper offers the resulting seven recommendations for
      reporting studies of tailored interventions. If we are to build a cumulative
      science of tailoring, both for theory development and research translation, then
      we should establish standards in the conduct and reporting of the science.

PMID- 22156231
TI  - Process evaluation results from the HEALTHY physical education intervention.
AB  - Process evaluation is an assessment of the implementation of an intervention. A
      process evaluation component was embedded in the HEALTHY study, a primary
      prevention trial for Type 2 diabetes implemented over 3 years in 21 middle
      schools across the United States. The HEALTHY physical education (PE)
      intervention aimed at maximizing student engagement in moderate-to-vigorous
      physical activity through delivery of structured lesson plans by PE teachers.
      Process evaluation data collected via class observations and interventionist
      interviews assessed fidelity, dose delivered, implementor participation, dose
      received and barriers. Process evaluation results indicate a high level of
      fidelity in implementing HEALTHY PE activities and offering 225 min of PE every
      10 school days. Concerning dose delivered, students were active for approximately
      33 min of class, representing an average of 61% of the class time. Results also
      indicate that PE teachers were generally engaged in implementing the HEALTHY PE
      curriculum. Data on dose received showed that students were highly engaged with
      the PE intervention; however, student misbehavior was the most common barrier
      observed during classes. Other barriers included teacher disengagement, large
      classes, limited gym space and poor classroom management. Findings suggest that
      the PE intervention was generally implemented and received as intended despite
      several barriers.

PMID- 22156232
TI  - Tobacco in the news: associations between news coverage, news recall and smoking
      related outcomes in a sample of Australian smokers and recent quitters.
AB  - This paper aims to track smokers' and recent quitters' recall of tobacco news,
      compare patterns of recall with patterns of news coverage and assess associations
      between news recall and smoking-related cognitions and behaviours, by using a
      quantitative analysis. The Cancer Institute New South Wales (NSW)'s Tobacco
      Tracking Survey, a continuous tracking telephone survey of adult smokers and
      recent quitters, was used to monitor recall of tobacco news and smoking-related
      cognitions and behaviours from January to September 2010 (approximately 50
      interviews per week; n = 1952). Thirty per cent of respondents reported semi
      prompted recall of tobacco news with patterns of recall closely following peaks
      in news coverage. Television was the most frequently cited source of tobacco
      news. Multivariate logistic regression analyses indicated that, controlling for
      individual characteristics, smokers with high levels of tobacco news recall were
      significantly more likely to have strong beliefs about harms from smoking [odds
      ratio (OR) = 1.38] and frequent thoughts about quitting (OR = 1.32). The results
      show that the news media are an important source of information for smokers, with
      the potential to influence beliefs and to put or keep quitting on the smokers'
      agenda. Media advocacy remains an important component of tobacco control.

PMID- 22156233
TI  - Assessing sustainability of Lifestyle Education for Activity Program (LEAP).
AB  - Sustained intervention effects are needed for positive health impacts in
      populations; however, few published examples illustrate methods for assessing
      sustainability in health promotion programs. This paper describes the methods for
      assessing sustainability of the Lifestyle Education for Activity Program (LEAP).
      LEAP was a comprehensive school-based intervention that targeted change in
      instructional practices and the school environment to promote physical activity
      (PA) in high school girls. Previous reports indicated that significantly more
      girls in the intervention compared with control schools reported engaging in
      vigorous PA, and positive long-term effects on vigorous PA also were observed for
      girls in schools that most fully implemented and maintained the intervention 3
      years following the active intervention. In this paper, the seven steps used to
      assess sustainability in LEAP are presented; these steps provide a model for
      assessing sustainability in health promotion programs in other settings. Unique
      features of the LEAP sustainability model include assessing sustainability of
      changes in instructional practices and the environment, basing assessment on an
      essential element framework that defined complete and acceptable delivery at the
      beginning of the project, using multiple data sources to assess sustainability,
      and assessing implementation longitudinally.

PMID- 22156234
TI  - Mediating effects of home-related factors on fat intake from snacks in a school
      based nutrition intervention among adolescents.
AB  - The purpose of the present study was to investigate if the effects of the
      parental component of a school-based intervention on dietary fat intake from
      snacking were mediated by changes in home-related factors. A random sample of 10
      schools with 2232 pupils aged 11-15 years was randomly assigned to one of two
      intervention groups [one with (n = 1226) and one without a parental component (n
      = 1006)]. Fat intake, home availability of low-fat foods and parental
      encouragement and support to eat a low-fat diet were assessed with validated self
      administered questionnaires. Mediation was assessed with the product-of
      coefficient test. Changes in home-related determinants were significantly related
      to changes in fat intake from snacks; therefore, school-based obesity programmes
      on adolescents should try to address these determinants. In the present study,
      one of the three investigated home-related factors, namely parental support, was
      affected by the parental component intervention. Decreases in parental support
      were prevented. These changes in parental support were found to mediate the
      parental intervention effects on changes in fat intake from snacks. Home-related
      factors appear to be related to changes in adolescents' snacking behaviours,
      therefore, school-based obesity programmes should target them. Nevertheless, more
      research is needed concerning effectively addressing the other determinants.

PMID- 22156235
TI  - Parent and child characteristics related to chosen adolescent alcohol and drug
      prevention program.
AB  - Mothers were allowed to choose between two different family-based adolescent
      alcohol-drug prevention strategies and the choice was examined in relation to
      parent and teen characteristics. Under real world conditions, parents are making
      choices regarding health promotion strategies for their adolescents and little is
      known about how parent and teen characteristics interact with programs chosen.
      The two programs were: Family Matters (FM) (Bauman KE, Foshee VA, Ennett ST et
      al. Family Matters: a family-directed program designed to prevent adolescent
      tobacco and alcohol use. Health Promot Pract 2001; 2: 81-96) and Strengthening
      Families Program (SFP) 10-14 (Spoth R, Redmond C, Lepper H. Alcohol initiation
      outcomes of universal family-focused preventive interventions: one- and two-year
      follow-ups of a controlled study. J Stud Alcohol Suppl 1999; 13: 103-11). A total
      of 272 families with an 11-12 years old enrolled in health care centers were in
      the choice condition of the larger study. SFP requires group meetings at
      specified times and thus demanded more specific time commitments from families.
      In contrast, FM is self-directed through booklets and is delivered in the home at
      a time chosen by the families. Mothers were significantly more likely to choose
      SFP when the adolescent had more problem behaviors. Mothers with greater
      education were more likely to choose FM. Findings may provide more real-world
      understanding of how some families are more likely to engage in one type of
      intervention over another. This understanding offers practical information for
      developing health promotion systems to service the diversity of families in the
      community.

PMID- 22156236
TI  - Charged excitons, Auger recombination and optical gain in CdSe/CdS nanocrystals.
AB  - CdSe/CdS colloidal nanocrystals are members of a novel class of light-emitting
      nanoparticles with remarkable optical properties such as suppressed fluorescence
      blinking and enhanced emission from multiexciton states. These properties have
      been linked to the suppression of non-radiative Auger recombination. In this work
      we employ ultrafast spectroscopy techniques to identify optical signatures of
      neutral and charged excitonic and multiexcitonic states. We show that Auger
      recombination of biexcitons is not suppressed, while we observe optical gain and
      amplified spontaneous emission from multiexciton states and from long-lived
      charged-exciton states.

PMID- 22156237
TI  - Nonequilibrium conductance of a  nanodevice for small bias voltage.
AB  - Using nonequilibrium renormalized perturbation theory, we calculate the retarded
      and lesser self-energies, the spectral density rho(omega) near the Fermi energy,
      and the conductance G through a quantum dot as a function of a small bias voltage
      V, in the general case of electron-hole asymmetry and intermediate valence. The
      linear terms in omega and V are given exactly in terms of thermodynamic
      quantities. When the energies necessary to add the first electron (Ed) and the
      second one (Ed + U) to the quantum dot are not symmetrically placed around the
      Fermi level, G has a term linear in V if, in addition, either the voltage drop or
      the coupling to the leads is not symmetric. The effects of temperature are
      discussed. The results simplify for a symmetric voltage drop, a situation usual
      in experiment.

PMID- 22156238
TI  - Dual-energy digital radiography in the assessment of bone mechanical properties.
AB  - At present, bone fragility and fracture risk are estimated with bone mineral
      density (BMD), measured by dual-energy x-ray absorptiometry (DXA). It is known
      that DXA-based BMD (BMD(DXA)) has a relationship with mechanical characteristics
      of bone. Dual-energy digital radiography (DEDR) has also been shown to be a
      potential method to determine BMD, but the ability of DEDR-based BMD (BMD(DEDR))
      to predict bone mechanical properties is not yet known. In this study, we
      investigated the ability of BMD(DEDR) to predict the mechanical characteristics
      of bone. Reindeer femora (N = 50) were imaged at two different energies (79 and
      100 kV(p)) using a clinical digital radiography system. BMD was determined in
      four regions from these images using the DXA calculation principle. Femora were
      mechanically tested using axial loading configuration. Mechanical parameters were
      correlated with the BMD(DEDR) and BMD(DXA) of the femoral neck (FNBMD(DEDR) and
      FNBMD(DXA)). FNBMD(DEDR) and FNBMD(DXA) both correlated moderately with
      mechanical parameters. The highest correlations were found with maximal load (r =
      0.53 and r = 0.65, p < 0.01, respectively). No statistically significant
      differences were found between the correlation coefficients when comparing the
      FNBMD(DEDR) or FNBMD(DXA) values and mechanical parameters. The correlation
      coefficient between BMD(DEDR) and BMD(DXA) varied between r = 0.56 and 0.86 (p <
      0.01) in different regions of the upper femur. In conclusion, BMD(DEDR) predicts
      the mechanical parameters of reindeer bone with similar accuracy as BMD(DXA).

PMID- 22156239
TI  - Electrical characterization of graphene synthesized by chemical vapor deposition
      using Ni substrate.
AB  - In this work, the electrical characterization of graphene films grown by chemical
      vapor deposition (CVD) on a Ni thin film is carried out and a simple relation
      between the gate-dependent electrical transport and the thickness of the films is
      presented. Arrays of two-terminal devices with an average graphene film thickness
      of 6.9 nm were obtained using standard fabrication techniques. A simple two-band
      model is used to describe the graphene films, with a band overlap parameter E(0)
      = 17 meV determined by the dependence of conductivity on temperature. Statistical
      electrical measurement data are presented for 126 devices, with an extracted
      average background conductivity sigma = 0.91 mS, average carrier mobility MU =
      1300 cm(2) V(-1) s(-1) and residual resistivity rho = 1.65 kOmega. The ratio of
      mobility to conductivity is calculated to be inversely proportional to the
      graphene film thickness and this calculation is statistically verified for the
      ensemble of 126 devices. This result is a new method of graphene film thickness
      determination and is useful for films which cannot have their thickness measured
      by AFM or optical interference, but which are electrically contacted and gated.
      This general approach provides a framework for comparing graphene devices made
      using different fabrication methods and graphene growth techniques, even without
      prior knowledge of their uniformity or thickness.

PMID- 22156240
TI  - Investigation of the effects of commensurability on friction between concentric
      carbon nanotubes.
AB  - That a commensurate contact usually leads to greater friction than an
      incommensurate one is a commonly held view in nanotribology. However, this
      perception seems paradoxical as commensurability is found to have negligible
      effect on the energy dissipation in double-walled carbon nanotube (DWNT) based
      oscillators. Using molecular dynamics simulations, we investigate such a paradox
      from the viewpoint of the atomic origin of friction. It is revealed that the
      commensurability cannot have a pronounced effect on friction unless the intertube
      interaction strength and the energy corrugation exceed their critical values.
      Both the commensurate and incommensurate oscillators constructed from natural
      DWNTs with an intertube distance of about 3.4 A, may thus exhibit similar
      performance.

PMID- 22156241
TI  - Fluorescence detection of potassium ion using the G-quadruplex structure.
AB  - Oligonucleotides with sequences of human telomere DNA or thrombin binding aptamer
      (TBA) are known to form tetraplex structures upon binding the K(+) ion. 
      Structural changes associated with the formation of tetraplex assemblies led to
      the development of potassium-sensing oligonucleotide (PSO) probes, in which two
      fluorescent dyes were attached to both termini of particular oligonucleotide. 
      The combination of dyes included fluorescence resonance energy transfer (FRET)
      and excimer emission approaches, and the structural changes upon binding K(+) ion
      could be monitored by a fluorescence technique.  These systems showed a very high
      preference for K(+) over Na(+) ion, which was suitable for fluorescence imaging
      of the potassium concentration gradient in a living cell.  In the case of human
      telomere DNA, it was also possible to follow the polymorphism of its tetraplex
      structures.

PMID- 22156242
TI  - Microchip-based plasma separation from whole blood via axial migration of blood
      cells.
AB  - Highly efficient cell-free plasma separation from 200 uL of human whole blood was
      realized via axial migration of blood cells and cross-flow filtration in a
      microchip.  Although various analyses of small volumes of blood have been
      reported, a large volume of blood is necessary for obtaining blood cells and
      plasma for the conventional plasma separation technique of centrifugation.  A
      highly efficient plasma separation method using small volumes of blood without
      hemolysis is an important issue.  We developed a plasma separation method based
      on a microchip with a filter, which utilizes the axial migration of blood cells
      observed in blood vessels.  Clogging and hemolysis on the filter can be prevented
      by the axial migration of the blood cells.  Using this method, 65% of the plasma
      from 200 uL of whole blood was successfully separated without hemolysis.  When
      the plasma separation microchip interfaced with a micro-ELISA system was applied
      to C-reactive protein (CRP) analysis, the CRP concentration obtained by the
      microchip showed good correlation with that obtained by conventional
      centrifugation.  Total analysis time, including plasma separation, was achieved
      in only 25 min.

PMID- 22156243
TI  - Signal enhancement by a multi-layered substrate for mutagen detection using an
      SOS response-induced green fluorescent protein in genetically modified
      Escherichia coli.
AB  - In this paper, we describe a method to enhance the fluorescence signal of mutagen
      detection using SOS response-induced green fluorescence protein (GFP) in
      genetically modified Escherichia coli using a multi-layered substrate.  To
      generate E. coli that express SOS response-induced GFP, we constructed a plasmid
      carrying the RecA promoter located upstream of the GFP gene and used it to
      transform E. coli BL21.  The transformed strain was incubated with mitomycin C
      (MMC), a typical mutagen, and then immobilized on a multi-layered substrate with
      Ag and a thin Al(2)O(3) layer on a glass slide.  Since the multi-layered
      substrate technique is an optical technique with potential to enhance the
      fluorescence of fluorophore placed on top of the substrate, the multi-layered
      substrate was expected to improve the fluorescence signal of mutagen detection. 
      We obtained an average 14-fold fluorescence enhancement of MMC-induced GFP in the
      concentration range 1 to 1000 ng/ml.  In addition, the lower detection limit of
      MMC was improved using this technique, and was estimated to be 1 ng/ml because of
      an enlargement of the difference between the blank and the signal of 1 ng/ml of
      MMC.

PMID- 22156244
TI  - Simple chemiluminescence aptasensors based on resonance energy transfer.
AB  - In the present work, two aptamer-based probes and related sensor systems were
      developed with chemiluminescence signaling.  The detection was based on "turning
      on" chemiluminescence with switching "off" of the resonance energy transfer after
      the aptamer's recognition of the target molecule.  In this design, a DNA/aptamer
      duplex linked a chemiluminescence group and a gold nanoparticle together.  Only
      low-intensity chemiluminescence was obtained due to the highly efficient
      resonance energy transfer.  After introducting the target molecule, structure
      switching took place with turning off the energy transfer; thus, a restoration
      and turning on of the chemiluminescence was obtained.  The two designs differed
      in the chemiluminescence groups, since one was a covalently linked luminol
      molecule, while the other was a conjugated horseradish peroxidase for the
      catalysis of further chemiluminescence reactions.  These schemes provided simple
      and effective sensing toward a model analyte, adenosine.

PMID- 22156245
TI  - Instrumentation of a PLC-regulated temperature cycler with a PID control unit and
      its use for miniaturized PCR systems with reduced volumes of aqueous sample
      droplets isolated in oil phase in a microwell.
AB  - We have developed a temperature cycler for polymerase chain reaction (PCR) in a
      microwell fabricated on a polymer/glass chip.  The entire system consisted of
      three subsystems, which included (1) a thermal conditioner, (2) a proportional
      integral-derivative (PID) control signal conditioner and (3) a data acquisition
      subsystem.  The subsystems were regulated coordinately by a ladder logic program
      written for the programmable logic control (PLC) so that an actual sample
      temperature could be timed, changed and maintained according to the programmed
      temperature cycles.  The present temperature control system showed high accuracy,
      stability and minimum overshoot with reduced heating and cooling transition
      rates.  Applicability of the temperature controller to the miniaturized PCR
      system with reduced volumes of aqueous sample droplets isolated in an oil phase
      was confirmed by successful amplifications of a target DNA sequence in the
      microwell.

PMID- 22156247
TI  - Vitamin U-bonded stationary phase in capillary ion chromatography.
AB  - A vitamin U-bonded stationary phase was prepared and the retention behavior of
      inorganic anions was examined using ion chromatography.  Inorganic anions were
      retained on the vitamin U-bonded stationary phase under acidic as well as neutral
      eluent conditions in the ion-exchange mode.  The elution order of the examined
      anions under neutral eluent conditions was nearly the same as that observed in
      common ion exchange mode, while the elution order observed under acidic eluent
      conditions was completely different from that observed in common ion exchange
      mode.  The retention of the analyte anions under the neutral eluent conditions
      was due to the sulfonium groups of the vitamin U, while protonated primary amino
      groups caused retention of the analyte anions with different selectivity under
      acidic conditions.  The retention factor of the analyte anions increased with
      decreasing eluent concentration under both eluent conditions.  The present system
      was applied to the determination of bromide and nitrate contained in seawater.

PMID- 22156246
TI  - Flow injection spectrophotometric determination of sub-mg dm(-3) silver(I) in a
      strongly acidic solution containing concentrated copper(II) using a pyridylazo
      reagent.
AB  - A novel spectrophotometric flow injection method for determination of silver(I)
      in a strongly acidic solution containing concentrated copper(II) was developed
      using a coloring ligand, 4-(3,5-dibromo-2-pyridylazo)-N-ethyl-N-(3
      sulfopropyl)aniline (3,5-diBr-PAESA). The method was first investigated by batch
      method. The interference from copper(II) chelate could be eliminated by the
      masking effect of EDTA. By utilizing the large formation constant (K = 12.3) of
      AgBr, one could determine silver(I) as a decrease of absorption by silver(I)
      chelate due to formation of AgBr by addition of KBr. Based on the results of
      batch experiments, two types of flow injection analysis (FIA) systems were
      constructed. Sub-mg dm(-3) determination of silver(I) was attained without
      interference from excess copper(II). The proposed method was successfully applied
      to determination of silver in a copper plating solution used in a plant to
      manufacture copper printed circuit boards, where the concentration of silver was
      critically important in the process control.

PMID- 22156248
TI  - Ion-pair formation between Cd(II), Na(I), and Ag(I) complex ions with 18-crown-6
      ether derivatives and various pairing anions in water: an understanding of the
      ion-pair formation based on the HSAB principle.
AB  - The ion-pair formation constants (K(MLX)(0)/mol(-1) dm(3)) of CdL(2+) with Br(-)
      or NaL(+) with N,N-diethyldithiocarbamate ion (DDTC(-)) in water were determined
      potentiometrically at 25 degrees C; ionic strength (I)->0: L denotes 18-crown-6
      ether (18C6) and its mono-benzo derivative for the CdBr(2)-L system and 15-crown
      5 ether and 18C6 for the NaDDTC-L one. The formation constant corresponding to
      the simple salt, NaDDTC, in water was also determined at I->0. Using the log
      K(CdLX)(0) values of CdLCl(+), CdLBr(+), CdLPic(+), and CdLSO(4), then CdL(2+)
      and picrate ion (Pic(-)) in water have been classified with the hard and soft
      acids and bases principle, where the values were available in the literature,
      except for CdLBr(+). The same classification was examined in NaX-L systems with
      X(-) = DDTC(-), trifluoroacetate ion, MnO(4)(-), ReO(4)(-), Pic(-), and BPh(4)(-)
      and the AgPic-L one. Consequently, CdL(2+), NaL(+), and AgL(+) were classified as
      the hard acids, while Pic(-) and BPh(4)(-) as the hard bases. These results
      reflected the reactivities of the complex ions in ion-pair formation with X(-)
      and SO(4)(2-) in water.

PMID- 22156249
TI  - Chemical dosimetry system for gamma-ray irradiation based on the formation of
      phenol from aqueous benzene solutions.
AB  - A chemical dosimetry system based on the radiochemical formation of phenol from
      aqueous benzene solutions was applied to measure the intensity of gamma-ray
      irradiation.  Using a simple and sensitive isocratic fluorometric HPLC system,
      radiochemically generated phenol was determined.  The radiochemical formation of
      phenol was linear up to 100 Gy and the lower limit of detection calculated from
      the detection limits of phenol was estimated to be 7 mGy.  The phenol formation
      rates were not affected by the oxygen saturation.  The chemical dosimetry system
      investigated in this study was sensitive and was easier to use than traditional
      chemical dosimeters.

PMID- 22156250
TI  - Preparation and evaluation of a chrysotile asbestos-containing standard material
      for validating x-ray diffractometric quantitation.
AB  - A standard material containing chrysotile asbestos for the validation of x-ray
      diffractometric quantitation was developed using an asbestos-containing building
      material i.e., perlite board. The board as the base material was crushed,
      pulverized, and homogenized. The homogeneity of the powder of perlite board was
      estimated by analysis of variance. The diffraction intensity values of the
      crystalline phases and the concentrations of elements determined by x-ray
      diffractometry and x-ray fluorescence analysis were used for analysis of
      variance. There is no significant difference between the within-bottle variance
      and the between-bottle variance, indicating that the powdered perlite board was
      sufficiently homogenous. The concentration of chrysotile in the material was
      determined using two methods: an internal standard/x-ray diffractometry method
      and the x-ray diffractometry/Rietveld refinement. The concentration of chrysotile
      in the material was determined by an internal standard/x-ray diffractometry
      method and the material had a chrysotile concentration of 24.1 +/- 0.2 mass%.

PMID- 22156251
TI  - Electrochemical determination of nitrite and iodate based on Pt nanoparticles
      self-assembled on a chitosan modified glassy carbon electrode.
AB  - A promising electrochemical sensor was fabricated by the self-assembling of Pt
      nanoparticles (nano-Pts) on a chitosan (CS) modified glassy carbon electrode
      (GCE). A field-emission scanning electron microscope (FE-SEM), transmission
      electron microscopy (TEM) and electrochemical techniques were used for
      characterization of these composites. It has been found that nano-Pts are
      inserted into the CS layer uniformly, and have a larger surface area compared to
      the chitosan modified glassy carbon electrode. Electrocatalytic experiments for
      the oxidation of nitrite and the reduction of iodate have shown that nano
      Pts/CS/GCE can decrease the over-potential and increase the faradic current,
      which can be used for the sensitive determination of nitrite and iodate.
      Moreover, the prepared modified electrode exhibits good reproducibility and
      stability, and it is possible that this novel electrochemical sensor can be
      applied in the sensing and/or biosensing field.

PMID- 22156252
TI  - Quartz crystal microbalance detection of DNA single-base mutation based on
      monobase-coded cadmium tellurium nanoprobe.
AB  - A new method for the detection of point mutation in DNA based on the monobase
      coded cadmium tellurium nanoprobes and the quartz crystal microbalance (QCM)
      technique was reported. A point mutation (single-base, adenine, thymine,
      cytosine, and guanine, namely, A, T, C and G, mutation in DNA strand,
      respectively) DNA QCM sensor was fabricated by immobilizing single-base mutation
      DNA modified magnetic beads onto the electrode surface with an external magnetic
      field near the electrode. The DNA-modified magnetic beads were obtained from the
      biotin-avidin affinity reaction of biotinylated DNA and streptavidin
      functionalized core/shell Fe(3)O(4)/Au magnetic nanoparticles, followed by a DNA
      hybridization reaction. Single-base coded CdTe nanoprobes (A-CdTe, T-CdTe, C-CdTe
      and G-CdTe, respectively) were used as the detection probes. The mutation site in
      DNA was distinguished by detecting the decreases of the resonance frequency of
      the piezoelectric quartz crystal when the coded nanoprobe was added to the test
      system. This proposed detection strategy for point mutation in DNA is proved to
      be sensitive, simple, repeatable and low-cost, consequently, it has a great
      potential for single nucleotide polymorphism (SNP) detection.

PMID- 22156253
TI  - Disposable screen-printed bismuth electrode modified with multi-walled carbon
      nanotubes for electrochemical stripping measurements.
AB  - Integrating the advantages of screen printing technology with the encouraging
      electroanalytical characteristic of metallic bismuth, we developed an
      ultrasensitive and disposable screen-printed bismuth electrode (SPBE) modified
      with multi-walled carbon nanotubes (MWCNTs) for electrochemical stripping
      measurements. Metallic bismuth powders and MWCNTs were homogeneously mixed with
      graphite-carbon ink to mass-prepare screen-printed bismuth electrode doped with
      multi-walled carbon nanotubes (SPBE/MWCNT). The electroanalytical performance of
      the prepared SPBE/MWCNT was intensively evaluated by measuring trace Hg(II) with
      square-wave anodic stripping voltammetry (SWASV). The results indicated that the
      SPBE modified with 2 wt% MWCNTs could offer a more sensitive response to trace
      Hg(II) than the bare SPBE. The stripping current obtained at SPBE/MWCNT was
      linear with Hg(II) concentration in the range from 0.2 to 40 ug/L (R(2) =
      0.9976), with a detection limit of 0.09 ug/L (S/N = 3) under 180 s accumulation.
      The proposed "mercury-free" electrode, with extremely simple preparation and
      ultrahigh sensitivity, holds wide application prospects in both environmental and
      industrial monitoring.

PMID- 22156254
TI  - Enhancement of vindoline production in suspension culture of the Catharanthus
      roseus cell line C20hi by light and methyl jasmonate elicitation.
AB  - The effects of light and methyl jasmonate (MJ) on the transcription of
      biosynthetic genes as well as the accumulation of vindoline and catharanthine in
      Catharanthus roseus C20hi cell suspensions were studied. t16h (the gene encoding
      tabersonine 16-hydroxylase) could be induced by light and MJ, whereas d4h (the
      gene encoding deacetoxyvindoline 4-hydroxylase) could only be induced by light.
      Quantification by UPLC-MS showed that light significantly increased vindoline
      production in C20hi cells by about 0.49 - 5.51-fold more than that in controls,
      with the highest yield being 75.3 ng/g of dry weight. The biosynthesis of
      vindoline was further enhanced by combining MJ with light. The accumulation of
      catharanthine was not improved by either light or MJ elicitation. These results
      suggested that light and MJ could promote vindoline, but not catharanthine
      accumulation in C20hi cells.

PMID- 22156255
TI  - Enhancement of the luminescence efficiency of europium(III) tris(beta-diketonato)
      complex in organic media by quaternary ammonium salts with anionic ligands.
AB  - Benzyldimethyltetradecylammonium (BA14(+)) salts with anionic ligands (X(-)),
      such as bis(2-ethylhexyl)sulfosuccinate, bis(2-ethylhexyl)phosphate (BEHP(-)),
      and benzotriazole (BTA(-)) anions, were prepared.  These salts were soluble in
      various organic solvents.  The luminescence emission spectra of organic solutions
      of a red luminescent, tris(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6
      octadionato)europium(III) complex in the presence of the BA14X's were recorded. 
      The emission intensity of the Eu(III) complex was increased remarkably by the
      addition of BA14X (X(-) = BEHP(-) and BTA(-)).  This effect can be attributed to
      the formation of 1:1 X(-)-adducts of the Eu(III) complex, in which the asymmetry
      of the ligand field is increased so as to enhance the emission efficiency of the
      (5)D(0)->(5)F(2) transition.  The enhancement effect by BA14X was higher than
      that of charge-neutral ligands, such as tri-n-octylphosphine oxide and 1,10
      phenanthroline, which have been used as second ligands to enhance the emission
      efficiency of tris(beta-diketonato)europium(III) complexes.

PMID- 22156256
TI  - Mass transfer of water-insoluble organic compound from octadecylsilyl-silica gel
      into water in the presence of a nonionic surfactant.
AB  - The release of perylene from octadecylsilyl (ODS)-silica gel into water using a
      nonionic surfactant was kinetically studied by single microparticle injection and
      absorption microspectroscopy techniques.  The release of perylene from the porous
      microparticles significantly depended on the surfactant concentration.  The
      release rate constant was inversely proportional to the microparticle radius; the
      rate-determining step was the process at the spherical microparticle surface. 
      The mechanism is discussed in terms of the solubilization of perylene at the
      microparticle surface by the micelle.

PMID- 22156257
TI  - An abnormal temperature dependence of alkylpyrazines' retention in reversed-phase
      liquid chromatography.
AB  - Retention behaviors of pyrazine and alkylpyrazines on various stationary phases
      in reversed-phase liquid chromatography were examined. An abnormal temperature
      effect on the retention of alkylpyrazines with a mobile phase consisting of
      acetonitrile and water was observed when changing the column temperature. On the
      other hand, no similar trend was found with a methanol-water mobile phase. For
      all the columns investigated in this work, the above tendency to the temperature
      dependence was consistently observed, suggesting that the abnormal temperature
      effect on the retention of alkylpyrazines could be mainly induced by an
      acetonitrile-based mobile phase.

PMID- 22156258
TI  - [Screening methods for ion-channels drug discovery and new ideas].

PMID- 22156259
TI  - [Visualizing voltage dynamics in Zebrafish heart].

PMID- 22156260
TI  - [Automated electrophysiological system for the measurement of transporter/channel
      activities].

PMID- 22156261
TI  - [Recent efforts for the attainment of a single standard of clinical studies
      (intervention)].

PMID- 22156262
TI  - [The Asian Study Clinical Trial: a step towards introducing global standards for
      clinical research in Japan].

PMID- 22156263
TI  - [Science of new drug development and regulatory review].

PMID- 22156264
TI  - A new first principles approach to  calculate phonon spectra of disordered 
      alloys.
AB  - The lattice dynamics in substitutional disordered alloys with constituents having
      large size differences is driven by strong disorder in masses, inter-atomic force
      constants and local environments. In this paper, a new first principles approach
      based on special quasirandom structures and an itinerant coherent potential
      approximation to compute the phonon spectra of such alloys is proposed and
      applied to Ni0.5Pt0.5 alloy. The agreement between our results and experiments is
      found to be much better than for previous models of disorder due to an accurate
      treatment of the interplay of inter-atomic forces among various pairs of chemical
      species. This new formalism serves as a potential solution to the longstanding
      problem of a proper microscopic understanding of lattice dynamical behavior of
      disordered alloys.

PMID- 22156265
TI  - Optimize the field emission character of a vertical few-layer graphene sheet by
      manipulating the morphology.
AB  - Vertical few-layer graphene (FLG) sheets have been fabricated by using microwave
      plasma-enhanced chemical vapour deposition. Their shape was manipulated through
      adjusting the growth time and hydrocarbon gas ratio. The growth mechanism during
      different growth stages is discussed. The field emission characteristics for
      different FLG shapes were tested and found to be strongly influenced by the tip
      shape, the height and the amorphous carbon content. The optimal shape of vertical
      FLG for field emission had fewer layers, sharp corners, large height and was free
      of amorphous carbon. The best field emission properties with the optimal shape
      were observed with a turn-on field of 1:8 V MUm(-1) and maximum current density
      of 7 mA cm(-2).

PMID- 22156266
TI  - The 2011 BJA/PGA supplement: a selection of nine educational reviews.

PMID- 22156267
TI  - Perioperative management of patients with cardiac implantable electronic devices.
AB  - Many anaesthesia practitioners caring for patients with a cardiac implantable
      electronic device (CIED) lack the knowledge, experience, and requisite
      programming devices to independently manage these patients perioperatively. A
      recently updated ASA task force Practice Advisory presents expert opinion
      regarding the perioperative management of patients with CIEDs, and the Heart
      Rhythm Society (HRS) recently published a consensus statement on this subject in
      collaboration with the ASA, American Heart Association (AHA), and Society of
      Thoracic Surgeons (STS). The main intent of these documents is to provide
      recommendations that promote safe management of patients with CIEDs throughout
      the perioperative period and reduce the likelihood of adverse outcomes. Reviews
      of this topic focusing on the actions of the anaesthesiologist have been
      published, but a multidisciplinary approach to the perioperative management is
      now advocated. In emergent situations, however, or when there is no time for the
      requisite consultations, and in practice settings where the suggested
      multidisciplinary approach is simply not feasible, the anaesthesia team must
      still provide effective, safe perioperative management. Thus, all
      anaesthesiologists should become familiar with the basics of the current CIED
      technology and the essential tenets of perioperative CIED management. This review
      discusses relevant advances in CIED technology and practical perioperative
      management as outlined in the 2011 ASA Practice Advisory and HRS consensus
      statement.

PMID- 22156268
TI  - Multimodal therapies for postoperative nausea and vomiting, and pain.
AB  - Postoperative nausea and vomiting (PONV) and pain are two of the major concerns
      for patients presenting for surgery. The causes of PONV are multifactorial and
      can largely be categorized as patient risk factors, anaesthetic technique, and
      surgical procedure. Antiemetics work on several different receptor sites to
      prevent or treat PONV. This is probably why numerous studies have now
      demonstrated that using more than one antiemetic is usually more effective and
      results in fewer side-effects than simply increasing the dose of a single
      antiemetic. A multimodal approach to PONV should not be limited to drug therapy
      alone but should involve a holistic approach starting before operation and
      continuing intraoperatively with risk reduction strategies to which are added
      prophylactic antiemetics according to the assessed patient risk for PONV. With
      the increasing understanding of the pathophysiology of acute pain, especially the
      occurrence of peripheral and central hypersensitization, it is unlikely that a
      single drug or intervention is sufficiently broad in its action to be adequately
      effective, especially with moderate or greater pain. Although morphine and its
      congeners are usually the foundation of pain management regimens, as their dose
      increases so does the incidence of side-effects. Thus, the approach for the
      management of acute postoperative pain is to use multiple drugs or modalities
      (e.g. regional anaesthesia) to maximize pain relief and reduce side-effects.

PMID- 22156269
TI  - beta-Blockade in the perioperative management of the patient with cardiac disease
      undergoing non-cardiac surgery.
AB  - The cardiology literature has suggested for decades that beta-blockade protects
      patients with ischaemic heart disease. Extending this concept to perioperative
      patients initially produced promising results, with reductions in perioperative
      myocardial ischaemia and longer-term cardiovascular complications observed in
      several small randomized trials. However, subsequent larger trials have either
      shown no benefit or greater morbidity (especially stroke), despite reductions in
      cardiovascular events. Retrospective database analyses have confirmed or disputed
      these findings. Speciality societies, most importantly, the American Heart
      Association/American College of Cardiology Foundation, have promulgated
      guidelines for perioperative beta-blockade, which have been revised, as the
      evidence has changed. While the European guidelines continue to emphasize
      perioperative beta-blockade in high-risk patients, the American guidelines have
      reduced the strength and breadth of recommendations, focusing on haemodynamic
      titration. Future work will need to focus on identifying populations most likely
      to benefit or to be harmed, including pharmacogenetic analyses and distinctions
      between individual beta-blockers.

PMID- 22156270
TI  - What is really dangerous: anaemia or transfusion?
AB  - Summary While complex physiological mechanisms exist to regulate and optimize
      tissue oxygenation under various conditions, clinical and experimental evidence
      indicates that anaemia, unchecked, is associated with organ injury and
      unfavourable outcomes. More data (especially from human studies) are needed to
      answer questions regarding the optimal approaches to the treatment of acute and
      chronic anaemia. Meantime, allogeneic blood transfusions remain the most common
      treatment, particularly in surgical/trauma patients and those with moderate-to
      severe anaemia. Clinical studies emphasize the paradox that both anaemia and
      transfusion are associated with organ injury and increased morbidity and
      mortality across a wide span of disease states and surgical interventions.
      Further characterization of the mechanisms of injury is needed to appropriately
      balance these risks and to develop novel treatment strategies that will improve
      patient outcomes. Here, we present the current understanding of the physiological
      mechanisms of tissue oxygen delivery, utilization, adaptation, and survival in
      the face of anaemia and current evidence on the independent (and often,
      synergistic) deleterious impact of anaemia and transfusion on patient outcomes.
      The risks of anaemia and transfusion in the light of substantial variations in
      transfusion practices, increasing costs, shrinking pool of donated resources, and
      ambiguity about actual clinical benefits of banked allogeneic blood demand better
      management strategies targeted at improving patient outcomes.

PMID- 22156271
TI  - Development and potential clinical impairment of ultra-short-acting neuromuscular
      blocking agents.
AB  - Developing a non-depolarizing neuromuscular blocking agent that, like
      succinylcholine, has a rapid onset and a short duration of effect remains a goal
      of ongoing research. While rocuronium fills a portion of this need, the large
      doses required for rapid intubation render it a much longer-acting neuromuscular
      blocking agent. Postoperative residual neuromuscular block (NMB) is an
      increasingly recognized complication of non-depolarizing neuromuscular blocking
      agents. This occurs because of dosing choices for neuromuscular blocking agents
      and anticholinesterases as well as insensitivity of typically used monitors of
      depth of NMB. While antagonism of NMB is necessary with partial recovery, it is
      unnecessary with more complete recovery. Even when monitoring with an
      accelerograph, reversal of NMB is complicated. In addition to the
      pharmacodynamics of the individual neuromuscular blocking agents, factors such as
      timing of anticholinesterase administration, dose of anticholinesterase,
      concomitant medications, electrolyte abnormalities, and hepatic or renal disease
      can influence the degree of reversal. Sugammadex works differently than
      anticholinesterases and, when administered in appropriate doses, can reverse even
      profound block induced with vecuronium or rocuronium. Two new fumarate
      neuromuscular blocking agents have a rapid onset of effect and can be reversed at
      any time by administration of cysteine, which could significantly reduce the risk
      of postoperative residual NMB.

PMID- 22156272
TI  - Anaesthetic considerations for non-obstetric surgery during pregnancy.
AB  - Surgery during pregnancy is complicated by the need to balance the requirements
      of two patients. Under usual circumstances, surgery is only conducted during
      pregnancy when it is absolutely necessary for the wellbeing of the mother, fetus,
      or both. Even so, the outcome is generally favourable for both the mother and the
      fetus. All general anaesthetic drugs cross the placenta and there is no optimal
      general anaesthetic technique. Neither is there convincing evidence that any
      particular anaesthetic drug is toxic in humans. There is weak evidence that
      nitrous oxide should be avoided in early pregnancy due to a potential association
      with pregnancy loss with high exposure. There is evidence in animal models that
      many general anaesthetic techniques cause inappropriate neuronal apoptosis and
      behavioural deficits in later life. It is not known whether these considerations
      affect the human fetus but studies are underway. Given the general considerations
      of avoiding fetal exposure to unnecessary medication and potential protection of
      the maternal airway, regional anaesthesia is usually preferred in pregnancy when
      it is practical for the medical and surgical condition. When surgery is indicated
      during pregnancy maintenance of maternal oxygenation, perfusion and homeostasis
      with the least extensive anaesthetic that is practical will assure the best
      outcome for the fetus.

PMID- 22156273
TI  - Perioperative management of the paediatric patient with coexisting neuromuscular
      disease.
AB  - Children with neuromuscular diseases present a wide range of clinical
      manifestations and clinical implications for the anaesthesiologist. Neuromuscular
      diseases in children affect muscle strength by either directly weakening the
      muscle fibrils or indirectly by a degenerative nerve supply and weak
      neuromuscular junction. Of the more than 200 neuromuscular disorders known, the
      vast majority are genetic in origin. This review focuses on four of the more
      common neuromuscular disorders with emphasis on their pathophysiology and
      clinical implications for anaesthesiologists: malignant hyperthermia, the
      muscular dystrophies (Duchenne's, Becker's, and Emery-Dreifuss), mitochondrial
      disorders, and cerebral palsy.

PMID- 22156274
TI  - Does regional anaesthesia really improve outcome?
AB  - In recent decades, a number of studies have attempted to determine whether
      regional anaesthesia offers convincing benefits over general anaesthesia.
      However, today we interpret meta-analyses more carefully, and it remains unclear
      whether regional anaesthesia reduces mortality. However, regional anaesthesia
      offers superior analgesia over opioid-based analgesia, and a significant
      reduction in postoperative pain is still a worthwhile outcome. Recent
      developments in technical aspects of regional anaesthesia have the potential to
      provide significant advantages for many patients in all age groups. Moreover,
      studies focusing on specific outcomes have shown benefits for regional
      anaesthesia used for surgery and postoperative analgesia.

PMID- 22156275
TI  - Regional anaesthesia in the patient receiving antithrombotic and antiplatelet
      therapy.
AB  - The actual incidence of neurological dysfunction resulting from haemorrhagic
      complications associated with neuraxial block is unknown. Although the incidence
      cited in the literature is estimated to be <1 in 150,000 epidural and <1 in
      220,000 spinal anaesthetics, recent surveys suggest that the frequency is
      increasing and may be as high as 1 in 3000 in some patient populations. Overall,
      the risk of clinically significant bleeding increases with age, associated
      abnormalities of the spinal cord or vertebral column, the presence of an
      underlying coagulopathy, difficulty during needle placement, and an indwelling
      neuraxial catheter during sustained anticoagulation (particularly with standard
      unfractionated heparin or low molecular weight heparin). The decision to perform
      spinal or epidural anaesthesia/analgesia and the timing of catheter removal in a
      patient receiving antithrombotic therapy is made on an individual basis, weighing
      the small, although definite risk of spinal haematoma with the benefits of
      regional anaesthesia for a specific patient. Coagulation status should be
      optimized at the time of spinal or epidural needle/catheter placement, and the
      level of anticoagulation must be carefully monitored during the period of
      neuraxial catheterization. Indwelling catheters should not be removed in the
      presence of therapeutic anticoagulation, as this appears to significantly
      increase the risk of spinal haematoma. Vigilance in monitoring is critical to
      allow early evaluation of neurological dysfunction and prompt intervention. An
      understanding of the complexity of this issue is essential to patient management.

PMID- 22156276
TI  - Sharp burnout failure observed in high current-carrying double-walled carbon
      nanotube fibers.
AB  - We report on the current-carrying capability and the high-current-induced thermal
      burnout failure modes of 5-20 MUm diameter double-walled carbon nanotube (DWNT)
      fibers made by an improved dry-spinning method. It is found that the electrical
      conductivity and maximum current-carrying capability for these DWNT fibers can
      reach up to 5.9 * 10(5) S m(-1) and over 1 * 10(5) A cm(-2) in air. In
      comparison, we observed that standard carbon fiber tended to be oxidized and
      burnt out into cheese-like morphology when the maximum current was reached, while
      DWNT fiber showed a much slower breakdown behavior due to the gradual burnout in
      individual nanotubes. The electron microscopy observations further confirmed that
      the failure process of DWNT fibers occurs at localized positions, and while the
      individual nanotubes burn they also get aligned due to local high temperature and
      electrostatic field. In addition a finite element model was constructed to gain
      better understanding of the failure behavior of DWNT fibers.

PMID- 22156277
TI  - A case of primary angiosarcoma of the lung presenting as a hemorrhagic bronchial
      tumor.
AB  - Pulmonary angiosarcomas are usually secondary tumors, and only a few primary
      cases have been reported. Effective strategies for treating this tumor have not
      been established, and the prognosis of affected individuals is generally very
      poor. We report a case of primary angiosarcoma presenting as a hemorrhagic
      solitary nodule at the bifurcation of the left main bronchus, followed for two
      years before surgery. Bronchial arteriography revealed a tumor stain sign, and
      racemose hemangioma of the bronchial artery was excluded. The hemoptysis was not
      controlled by repeated bronchial artery embolization, and the patient underwent
      left pneumonectomy with routine mediastinal lymph node dissection.
      Histopathologically, the excised tissue revealed a highly-cellular growth of
      atypical spindle cells with a storiform pattern. These atypical cells showed
      relatively low mitotic activity; the MIB-1 index was 10%. The tumor was diagnosed
      as a primary angiosarcoma of the lung by the following immunohistological
      findings: positivity for factor VIII-related antigen and CD31. One year after
      resection, the patient remains well without signs of recurrence.

PMID- 22156282
TI  - Apico-aortic conduit for aortic stenosis in a patient with chronic thoracic wall
      infection.
AB  - We report a case of an apico-aortic bioprothesis-valved conduit for a 70-year-old
      woman with symptomatic, severe aortic stenosis and severe calcification of the
      ascending aorta. She had a history of mastectomy and radiation therapy for breast
      cancer and was suffering from radiodermatitis and chronic thoracic wall
      infection. Transthoracic echocardiography showed severe aortic valve stenosis
      with heavy calcification and high aortic valve pressure gradients. In patients
      with a chronically infected thoracic wall, median sternotomy is considered to be
      a high risk procedure, resulting in postoperative mediastiniti; therefore, we
      applied a technique in which we used an apico-aortic conduit via posterolateral
      thoracotomy. We underwent apico-aortic bypass with a hand-made composite graft:
      19-mm bioprosthetic valve and a 22-mm woven polyester vascular graft. The
      surgical intervention successfully decreased pressure gradient across the aortic
      valve, also separating an incision from chronic infection allowed us to avoid
      postoperative mediastinitis. The patient had remained in good condition for 15
      months without developing any complications.

PMID- 22156284
TI  - Adult bicuspid aortic valve endocarditis with extensive paravalvular invasion
      attributable to disseminated varicella zoster infection.
AB  - We report a previously healthy 21-year-old man who developed disseminated
      varicella zoster infection complicated with encephalitis, acute renal
      insufficiency, liver dysfunction, and an apparent pustular skin superinfection
      with Staphylococcus aureus. He later developed an extensively destructive
      endocarditis affecting a congenital bicuspid aortic valve, accompanied with
      leaflet perforation, complete atrio-ventricular (AV) block, and invasion of
      vegetation to both left and right atrium; the endocarditis was attributed to the
      same skin pathogen, S. aureus. He underwent radical debridement of the aortic
      valve, membranous ventricular septum, and mitral anterior fibrous trigone,
      followed by reconstruction of intracardiac defects with 2 autologous pericardial
      patches and aortic valve replacement. After a permanent pacemaker implantation
      and 4 weeks of antibiotic treatment, he was discharged after an uneventful
      postoperative course.

PMID- 22156285
TI  - The "loop with anchor" technique to repair mitral valve prolapse.
AB  - The current surgical technique of using an artificial chord (composed of expanded
      polytetrafluoroethylene [ePTFE] sutures) to repair mitral prolapse is technically
      difficult to perform. Slippery knot tying and the difficulty of changing the
      chordae length after the hydrostatic test are frustrating problems. The loop
      technique solves the problem of slippery knot tying but not the problem of
      changing the chordae length. Our "loop with anchor" technique consists of the
      following elements: construction of an anchor at the papillary muscle;
      determining the loop length; tying the loop to the anchor; suturing the loop to
      the mitral valve; the hydrostatic test; and re-suturing or changing the loop, if
      needed. Adjustments can be made for the entire procedure or for a portion of the
      procedure.

PMID- 22156286
TI  - Necessity and readiness for smoking cessation intervention in dental clinics in
      Japan.
AB  - BACKGROUND: The necessity and readiness for smoking cessation intervention in
      dental clinics was assessed by investigating smoking status and stage of behavior
      change in patients and the attitudes of dentists toward the effects of smoking on
      their patients, respectively. METHODS: A self-administered questionnaire was
      mailed to 1022 dentists randomly selected from the Japanese Dental Association
      database. The questionnaire survey consisted of 1 section for dentists and 1 for
      patients aged 20 years or older and was scheduled to be completed at the
      dentists' clinics on a designated day in February 2008. RESULTS: The response
      rate to the questionnaire was 78.2% from among target dental clinics and 73.7%
      and 74.7% for patient and dentist questionnaires, respectively. Data from 11,370
      patients and 739 dentists were analyzed. The overall smoking prevalence among the
      patients (25.1%) was similar to that reported by the National Health and
      Nutrition Examination Survey, and young female patients had a markedly higher
      smoking prevalence. More than 70% of patients who smoked were interested in
      quitting. Although the prevalence of current smoking among dentists (27.1%) was
      significantly higher than that reported among Japanese physicians (15.0%),
      approximately 70% of dentists were concerned about the effects of smoking on
      patient health and prohibited smoking inside their clinic. CONCLUSIONS: Many
      smokers who were interested in quitting, particularly young women, visited dental
      clinics, and most dentists believed that smoking was harmful for their patients.
      These results indicate that smoking cessation intervention in dental settings is
      necessary and that dentists are ready to provide such interventions.

PMID- 22156287
TI  - Association between breastfeeding and dental caries in Japanese children.
AB  - BACKGROUND: Studies investigating the impact of breastfeeding on dental caries
      have produced contradictory results. This cross-sectional study investigated the
      relationship between breastfeeding and the prevalence of dental caries in young
      Japanese children. METHODS: The study subjects were 2056 Japanese children aged 3
      years. Information on breastfeeding was obtained by means of a questionnaire.
      Children were classified as having caries if 1 or more deciduous teeth were
      decayed, missing, or had been filled at the time of examination. RESULTS: The
      prevalence of dental caries was 20.7%. As compared with breastfeeding for less
      than 6 months, breastfeeding for 18 months or longer was associated with a
      significantly higher prevalence of dental caries. The relation was J-shaped: the
      adjusted prevalence ratios for less than 6 months, 6 to 11 months, 12 to 17
      months, and 18 months or longer were 1.0, 0.79 (95% confidence interval [CI]:
      0.60-1.05), 0.86 (95% CI: 0.66-1.13), and 1.66 (95% CI: 1.33-2.06), respectively
      (P for linear trend <0.0001, P for quadratic trend <0.0001). CONCLUSIONS:
      Breastfeeding for 18 months or longer was positively associated with the
      prevalence of dental caries, while breastfeeding for 6 to 17 months was
      nonsignificantly inversely associated with the prevalence of dental caries.

PMID- 22156288
TI  - Television viewing time is associated with overweight/obesity among older adults,
      independent of meeting physical activity and health guidelines.
AB  - BACKGROUND: Previous studies have shown associations of sedentary behavior with
      cardiovascular risk, independent of moderate-to-vigorous physical activity
      (MVPA). However, few studies have focused on older adults. This study examined
      the joint associations of television (TV) viewing time and MVPA with
      overweight/obesity among Japanese older adults. METHODS: A population-based,
      cross-sectional mail survey was used to collect self-reported height, weight,
      time spent in TV viewing, and MVPA from 1806 older adults (age: 65-74 years, men:
      51.1%). Participants were classified into 4 categories according to TV viewing
      time (dichotomized into high and low around the median) and MVPA level
      (dichotomized into sufficient and insufficient by the physical activity guideline
      level of >= 150 minutes/week). Odds ratios (ORs) for overweight/obesity (body
      mass index >= 25 kg/m2) were calculated according to the 4 TV/MVPA categories,
      adjusting for potential confounders. RESULTS: Of all participants, 20.1% were
      overweight/obese. The median TV viewing time (25th, 75th percentile) was 840
      (420, 1400) minutes/week. As compared with the reference category (high
      TV/insufficient MVPA), the adjusted ORs (95% CI) of overweight/obesity were 0.93
      (0.65, 1.34) for high TV/sufficient MVPA, 0.58 (0.37, 0.90) for low
      TV/insufficient MVPA, and 0.67 (0.47, 0.97) for low TV/sufficient MVPA.
      CONCLUSIONS: In this sample of older adults, spending less time watching TV, a
      predominant sedentary behavior, was associated with lower risk of being
      overweight or obese, independent of meeting physical activity guidelines. Further
      studies using prospective and/or intervention designs are warranted to confirm
      the presently observed effects of sedentary behavior, independent of physical
      activity, on the health of older adults.

PMID- 22156289
TI  - Epidemiologic studies of psychosocial factors associated with quality of life
      among patients with chronic diseases in Japan.
AB  - A link between affective disturbances and physical disorders has been suggested
      since the Greco-Roman era. However, evidence supporting an association between
      mind and body is limited and mostly comes from North America and Europe.
      Additional local epidemiologic studies are needed so that more evidence can be
      collected on effective treatments and health management. Epidemiologic studies of
      Japanese with rheumatoid arthritis (RA) and those on chronic hemodialysis
      examined the association between psychosocial factors and patient quality of life
      (QOL). Strong associations among depression, social support, and patient QOL were
      confirmed, which supports the findings of studies performed in Western countries.
      In addition, disparities between the perspectives of patients with RA and their
      doctors were observed. Alexithymia, a personality construct that reflects a
      deficit in the cognitive processing of emotion, had a stronger independent
      association with increased risk of 5-year mortality than did depression among
      patients with chronic hemodialysis. Physiological, biological, and psychosocial
      factors are associated and independently and interactively determine our health.
      Epidemiology is a powerful tool for identifying effective points of intervention,
      after considering all possible confounders. Future studies must clarify how
      health can be improved by using a psychosocial approach.

PMID- 22156290
TI  - Socioeconomic disparities and health: impacts and pathways.
AB  - Growing socioeconomic disparity is a global concern, as it could affect
      population health. The author and colleagues have investigated the health impacts
      of socioeconomic disparities as well as the pathways that underlie those
      disparities. Our meta-analysis found that a large population has risks of
      mortality and poor self-rated health that are attributable to income inequality.
      The study results also suggested the existence of threshold effects (ie, a
      threshold of income inequality over which the adverse impacts on health
      increase), period effects (ie, the potential for larger impacts in later years,
      specifically after the 1990s), and lag effects between income inequality and
      health outcomes. Our other studies using Japanese national representative survey
      data and a large-scale cohort study of Japanese older adults (AGES cohort)
      support the relative deprivation hypothesis, namely, that invidious social
      comparisons arising from relative deprivation in an unequal society adversely
      affect health. A study with a natural experiment design found that the
      socioeconomic gradient in self-rated health might actually have become shallower
      after the 1997-98 economic crisis in Japan, due to smaller health improvements
      among middle-class white-collar workers and middle/upper-income workers. In
      conclusion, income inequality might have adverse impacts on individual health,
      and psychosocial stress due to relative deprivation may partially explain those
      impacts. Any study of the effects of macroeconomic fluctuations on health
      disparities should also consider multiple potential pathways, including expanding
      income inequality, changes in the labor market, and erosion of social capital.
      Further studies are needed to attain a better understanding of the social
      determinants of health in a rapidly changing society.

PMID- 22156291
TI  - Cubical Mass-Spring Model design based on a tensile deformation test and
      nonlinear material model.
AB  - Mass-Spring Models (MSMs) are used to simulate the mechanical behavior of
      deformable bodies such as soft tissues in medical applications. Although they are
      fast to compute, they lack accuracy and their design remains still a great
      challenge. The major difficulties in building realistic MSMs lie on the spring
      stiffness estimation and the topology identification. In this work, the
      mechanical behavior of MSMs under tensile loads is analyzed before studying the
      spring stiffness estimation. In particular, the performed qualitative and
      quantitative analysis of the behavior of cubical MSMs shows that they have a
      nonlinear response similar to hyperelastic material models. According to this
      behavior, a new method for spring stiffness estimation valid for linear and
      nonlinear material models is proposed. This method adjusts the stress-strain and
      compressibility curves to a given reference behavior. The accuracy of the MSMs
      designed with this method is tested taking as reference some soft-tissue
      simulations based on nonlinear Finite Element Method (FEM). The obtained results
      show that MSMs can be designed to realistically model the behavior of
      hyperelastic materials such as soft tissues and can become an interesting
      alternative to other approaches such as nonlinear FEM.

PMID- 22156292
TI  - On mesh-free valley surface extraction with application to low frequency sound
      simulation.
AB  - Crease surfaces describe extremal structures of 3D scalar fields. We present a
      new region-growing-based approach to the meshless extraction of adaptive
      nonmanifold valley and ridge surfaces that overcomes limitations of previous
      approaches by decoupling point seeding and triangulation of the surface. Our
      method is capable of extracting valley surface skeletons as connected minimum
      structures. As our algorithm is inherently mesh-free and curvature adaptive, it
      is suitable for surface construction in fields with an arbitrary neighborhood
      structure. As an application for insightful visualization with valley surfaces,
      we choose a low frequency acoustics simulation. We use our valley surface
      construction approach to visualize the resulting complex-valued scalar pressure
      field for arbitrary frequencies to identify regions of sound cancellation. This
      provides an expressive visualization of the topology of wave node and antinode
      structures in simulated acoustics.

PMID- 22156293
TI  - Lack of association between hOGG1 Ser326Cys polymorphism and the risk of bladder
      cancer: a meta-analysis.
AB  - OBJECTIVE: In some but not all studies, hOGG1 Ser326Cys polymorphism has been
      reported to contribute to the risk of bladder cancer. To determine whether there
      is a significant association of hOGG1 Ser326Cys polymorphism with the
      susceptibility for bladder cancer, we performed a comprehensive meta-analysis.
      METHODS: The electronic PubMed, Medline and Springer databases were searched for
      publications on the association between hOGG1 Ser326Cys polymorphism and bladder
      cancer through to May 20, 2011. Seven case-control studies were identified,
      including 2,474 cases and 2,408 controls. From these identified publications,
      crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to
      estimate the strength of association using fixed- or random-effects models. Two
      investigators each extracted data and conducted the analysis independently.
      RESULTS: Overall, no significant associations were found between hOGG1 Ser326Cys
      polymorphism and bladder cancer in codominant models (GG vs. CC: OR 1.11, 95% CI
      0.74-1.66, p = 0.63; GC vs. CC: OR 1.07, 95% CI 0.80-1.41, p = 0.65). Similarly,
      no significant associations with bladder cancer were observed in the recessive
      model (GG vs. GC+CC: OR 1.05, 95% CI 0.65-1.70, p = 0.85), dominant model (GG+GC
      vs. CC: OR 1.07, 95% CI 0.87-1.32, p = 0.53) and allele model (G vs. C: OR 1.06,
      95% CI 0.90-1.26, p = 0.49). In the stratified analyses by ethnicity, control
      sources, pathology, Hardy-Weinberg equilibrium, significant associations were
      still not observed. CONCLUSIONS: The overall current literature on hOGG1
      Ser326Cys polymorphism and the risk of bladder cancer suggests no statistically
      significant association between the two. Additional primary studies may be
      necessary to provide evidence of any significant association between this
      specific polymorphism and bladder cancer.

PMID- 22156294
TI  - Efficient de novo assembly of large genomes using compressed data structures.
AB  - De novo genome sequence assembly is important both to generate new sequence
      assemblies for previously uncharacterized genomes and to identify the genome
      sequence of individuals in a reference-unbiased way. We present memory efficient
      data structures and algorithms for assembly using the FM-index derived from the
      compressed Burrows-Wheeler transform, and a new assembler based on these called
      SGA (String Graph Assembler). We describe algorithms to error-correct, assemble,
      and scaffold large sets of sequence data. SGA uses the overlap-based string graph
      model of assembly, unlike most de novo assemblers that rely on de Bruijn graphs,
      and is simply parallelizable. We demonstrate the error correction and assembly
      performance of SGA on 1.2 billion sequence reads from a human genome, which we
      are able to assemble using 54 GB of memory. The resulting contigs are highly
      accurate and contiguous, while covering 95% of the reference genome (excluding
      contigs <200 bp in length). Because of the low memory requirements and
      parallelization without requiring inter-process communication, SGA provides the
      first practical assembler to our knowledge for a mammalian-sized genome on a low
      end computing cluster.

PMID- 22156295
TI  - Whole-exome sequencing of human pancreatic cancers and characterization of
      genomic instability caused by MLH1 haploinsufficiency and complete deficiency.
AB  - Whole-exome sequencing (Exome-seq) has been successfully applied in several
      recent studies. We here sequenced the exomes of 15 pancreatic tumor cell lines
      and their matched normal samples. We captured 162,073 exons of 16,954 genes and
      sequenced the targeted regions to a mean coverage of 56-fold. This study
      identified a total of 1517 somatic mutations and validated 934 mutations by
      transcriptome sequencing. We detected recurrent mutations in 56 genes. Among
      them, 41 have not been described. The mutation rates varied widely among cell
      lines. The diversity of the mutation rates was significantly correlated with the
      distinct MLH1 copy-number status. Exome-seq revealed intensive genomic
      instability in a cell line with MLH1 homozygous deletion, indicated by a
      dramatically elevated rate of somatic substitutions, small insertions/deletions
      (indels), as well as indels in microsatellites. Notably, we found that MLH1
      expression was decreased by nearly half in cell lines with an allelic loss of
      MLH1. While these cell lines were negative in conventional microsatellite
      instability assay, they showed a 10.5-fold increase in the rate of somatic
      indels, e.g., truncating indels in TP53 and TGFBR2, indicating MLH1
      haploinsufficiency in the correction of DNA indel errors. We further analyzed the
      exomes of 15 renal cell carcinomas and confirmed MLH1 haploinsufficiency. We
      observed a much higher rate of indel mutations in the affected cases and
      identified recurrent truncating indels in several cancer genes such as VHL,
      PBRM1, and JARID1C. Together, our data suggest that MLH1 hemizygous deletion,
      through increasing the rate of indel mutations, could drive the development and
      progression of sporadic cancers.

PMID- 22156297
TI  - "Just visiting" Broadmoor.

PMID- 22156298
TI  - Doctors, patients and the human rights act.

PMID- 22156296
TI  - Global DNA hypomethylation coupled to repressive chromatin domain formation and
      gene silencing in breast cancer.
AB  - While genetic mutation is a hallmark of cancer, many cancers also acquire
      epigenetic alterations during tumorigenesis including aberrant DNA
      hypermethylation of tumor suppressors, as well as changes in chromatin
      modifications as caused by genetic mutations of the chromatin-modifying
      machinery. However, the extent of epigenetic alterations in cancer cells has not
      been fully characterized. Here, we describe complete methylome maps at single
      nucleotide resolution of a low-passage breast cancer cell line and primary human
      mammary epithelial cells. We find widespread DNA hypomethylation in the cancer
      cell, primarily at partially methylated domains (PMDs) in normal breast cells.
      Unexpectedly, genes within these regions are largely silenced in cancer cells.
      The loss of DNA methylation in these regions is accompanied by formation of
      repressive chromatin, with a significant fraction displaying allelic DNA
      methylation where one allele is DNA methylated while the other allele is occupied
      by histone modifications H3K9me3 or H3K27me3. Our results show a mutually
      exclusive relationship between DNA methylation and H3K9me3 or H3K27me3. These
      results suggest that global DNA hypomethylation in breast cancer is tightly
      linked to the formation of repressive chromatin domains and gene silencing, thus
      identifying a potential epigenetic pathway for gene regulation in cancer cells.

PMID- 22156299
TI  - The recent doctors' strikes in India: a point of view.

PMID- 22156300
TI  - An international view of surgically assisted conception and surrogacy tourism.
AB  - Modern medicine, specifically assisted reproductive technology (ART), has
      overtaken the law in many jurisdictions around the world. New technologies and
      practices open a Pandora's Box of ethical, religious, social and legal questions,
      and may present a variety of significant legal problems to the courts and
      legislators. Surrogate motherhood and pregnancy through ART have both attracted
      controversy. Some groups condemn ART and want it banned while its supporters
      acknowledge there is a need for legislative guidelines and regulations. A
      proposed statute, the Assisted Reproductive Technique Services Act, aimed at
      regulating reproductive technologies, including surrogacy arrangements, will be
      introduced in the Malaysian parliament, probably in 2012, and the Assisted
      Reproductive Technology (Regulation) Bill 2010 is already before the Indian
      parliament. This paper will discuss several of the potential socio-legal issues
      surrounding ART in the light of the complex situation, with a comparative
      analysis of the Malaysian, USA, UK and Indian positions.

PMID- 22156301
TI  - 2011 healthwatch student prize: report to the healthwatch AGM held on 18 October
      2011.

PMID- 22156302
TI  - Cancer cell metabolism.
AB  - Although the generation of a distinctive metabolic profile is a well-known aspect
      of cancer, the significance of these adaptations and their potential for
      exploitation for anticancer therapy has not been fully appreciated until
      recently. Many oncogenic changes known to affect intracellular signaling pathways
      play an active role in mediating these metabolic changes, which, in turn,
      function to support cancer cell growth and replication. In this chapter, we
      discuss the most current findings in cancer cell metabolism in terms of their
      impact on tumor cell growth as well as their potential for identifying new
      targets for therapeutic intervention.

PMID- 22156304
TI  - Central actions of substance P and related tachykinins.

PMID- 22156305
TI  - Rapid changes in functional responsiveness of the 5-HT system after single-dose
      and multiple-dose treatment with antidepressants: effects of maprotiline and
      oxaprotiline and its enantiomers.
AB  - Functional responsiveness to 5-HTP (L-5-hydroxytryptophan) and quipazine 24 h
      after one single dose and 24 h and 72 h after repeated administration (2.5 and 10
      mg/kg twice daily for 7 days) of maprotiline, oxaprotiline and its (+) and (-)
      enantiomers was tested in the rat. All compounds markedly increased the
      behavioural effects of 5-HTP 24 h after one single injection. This effect was
      further enhanced after repeated treatment. The response to quipazine was less
      consistently affected than the response to 5-HTP. Neither drug increased the
      response to quipazine 24 h after the last injection. However, maprotiline and
      oxaprotiline enhanced the quipazine-induced head-twitch 72 h after the withdrawal
      of subchronic treat ment, enantiomers failed to do so. This differential effect
      of drugs in respect to the interactions with 5-HTP and quipazine is, however, not
      understood at present. The results of this study indicate that only one single
      dose of antidepressants may change the functional respon siveness of the 5-HT
      system and that such changes occur rapidly. The results also provide a possible
      rationale for the suggested antidepressant activity of levoprotiline, the (-)
      enantiomer of oxaprotiline and otherwise biochemically inactive compound.

PMID- 22156306
TI  - The 5-HT3 receptor antagonists ICS 205-930 and GR38032F, putative anxiolytic
      drugs, differ from diazepam in their pharmacological profile.
AB  - The pharmacological profile of the two 5-HT(3) (5-hydroxytryptamine) receptor
      antagonists, the putative anxiolytics ICS 205-930 and GR38032F was compared with
      that of diazepam in four standard behavioural tests in rats. All the investigated
      drugs induced an anxiolytic effect in the passive avoidance test, having reduced
      the latency to re-enter the chamber previously associated with an inescapable
      footshock, and increased the time spent in that chamber. On the basis of the
      lowest effective dose, both ICS 205-930 and GR38032F were about 20 times more
      potent than diazepam, though the anxiolytic activity of either 5- HT(3) receptor
      antagonist was confined to a narrow dose range (ICS 205-930: 93.7-187.5 MUg/ kg,
      GR38032F: 125-375 MUg/kg), their higher doses having been ineffective. The
      anxiolytic effect of diazepam, but not of ICS 205-930, was abolished by
      flumazenil. In contrast to diazepam, neither ICS 205-930 nor GR38032F-both given
      in doses up to 20 mg/kg-showed any activity in the pentylenetetrazol-induced
      seizures, open field, and rota-rod tests. These results suggest that the 5-HT(3)
      receptor antagonists may represent a new class of anxiolytic drugs devoid of
      anticonvulsant, sedative or muscle-relaxant properties, and that their anxi
      olytic activity is not mediated by benzodiazepine receptors.

PMID- 22156307
TI  - Antagonizing the behavioural effects of drugs: a discussion with specific
      reference to benzodiazepines and alcohol.
AB  - It can be extremely difficult to interpret the results of experiments in which a
      treatment is found to antagonize the behavioural effects of a drug. This article
      discusses strategies that can be used to help identify the nature of the
      antagonism and examines what such experiments tell us about the mechanisms
      underlying the drug's behavioural effects. Examples are taken from research with
      both benzodiazepines and ethanol. It is suggested that behavioural studies using
      different strategies to reduce the effects of a drug will further enhance our
      understanding of the mechanisms mediating the drug's effects. Such studies will
      include comparisons between the effects of chronic drug exposure (tolerance
      studies), genetic manipulations, and pharmacological treatments.

PMID- 22156303
TI  - MicroRNAs in metabolism and metabolic diseases.
AB  - Aberrant cholesterol/lipid homeostasis is linked to a number of diseases
      prevalent in the developed world, including metabolic syndrome, type II diabetes,
      and cardiovascular disease. We have previously uncovered gene regulatory
      mechanisms of the sterol regulatory element-binding protein (SREBP) family of
      transcription factors, which control the expression of genes involved in
      cholesterol and lipid biosynthesis and uptake. Intriguingly, we recently
      discovered conserved microRNAs (miR-33a/b) embedded within intronic sequences of
      the human SREBF genes that act in a concerted manner with their host gene
      products to regulate cholesterol/lipid homeostasis. Indeed, miR-33a/b control the
      levels of ATP-binding cassette (ABC) transporter ABCA1, a cholesterol efflux pump
      critical for high-density lipoprotein (HDL) synthesis and reverse cholesterol
      transport from peripheral tissues. Importantly, antisense inhibition of miR-33 in
      mice results in elevated HDL and decreased atherosclerosis. Interestingly, miR
      33a/b also act in the fatty acid/lipid homeostasis pathway by controlling the
      fatty acid beta-oxidation genes carnitine O-octanoyltransferase (CROT),
      hydroxyacyl-coenzyme A-dehydrogenase (HADHB), and carnitine palmitoyltransferase
      1A (CPT1A), as well as the energy sensor AMP-activated protein kinase
      (AMPKalpha1), the NAD(+)-dependent sirtuin SIRT6, and the insulin signaling
      intermediate IRS2, key regulators of glucose and lipid metabolism. These results
      have revealed a highly integrated microRNA (miRNA)-host gene circuit governing
      cholesterol/lipid metabolism and energy homeostasis in mammals that may have
      important therapeutic implications for the treatment of cardiometabolic
      disorders.

PMID- 22156308
TI  - Effect of clovoxamine fumarate on the electrocardiogram.
AB  - The electrocardiographic effects of clovoxamine, an antidepressant that inhibits
      the neuronal uptake of both noradrenaline and 5-hydroxytryptamine, have been
      studied. High speed electrocardiograms were recorded on 28 patients with
      depressive illness before and after 4 weeks treatment with either clovoxamine or
      placebo. No patient had clinical evidence of cardiovascular disease. The ECG
      measurements were carried out blind to patient, treatment and treatment interval.
      No statistically significant changes in the sinus cycle length, PR, QRS and QTc
      intervals, or T-wave height were found after treatment with active drug or
      placebo, showing that clovoxamine has no clinically important effects on the ECG
      when given in therapeutic doses to patients free from serious physical disease.

PMID- 22156309
TI  - Evidence for the involvement of 5-HT1A receptors in the mediation of exploratory
      locomotor activity in the rat.
AB  - The 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT),
      0.1 mg/kg(-1) subcutaneously, produced a suppression of horizontal ('locomotion')
      and vertical ('rearing') activity, in an open field arena. This effect was
      partially antagonized by treatment with (-)pindolol, 2 mg/kg(-1) subcutaneously.
      (-)Pindolol by itself produced a small, but statistically significant suppression
      of locomotor activity. There were no effects on rearing activity by (-)pindolol.
      In comparison with saline-treated controls, 8-OH-DPAT increased peripheral,
      relative to total, horizontal activity in the open field arena. (-)Pindolol
      adminis tration restored this pattern of activity to normal levels in 8-OH-DPAT
      treated animals, without altering the relation peripheral to total activity by
      itself.

PMID- 22156310
TI  - Potentiation of the pressor effect of oral and intravenous tyramine during
      administration of the selective MAO-A inhibitor moclobemide in healthy
      volunteers.
AB  - The interaction between tyramine and the new short-acting and reversible mono
      amine oxidase inhibitor moclobemide was investigated in a double-blind placebo
      controlled study in six healthy volunteers. There were two consecutive study
      periods of 8 days during which the subjects received moclobemide three x 200 mg
      daily or placebo. On day 5 of each study period changes in systolic blood
      pressure (SBP) were determined after incremental intravenous bolus doses of
      tyramine and on days 6, 7 and 8 changes in SBP were determined after oral
      tyramine (100, 200 and 300 mg, respectively). Oral tyramine was administered
      together with a standard breakfast, before which moclobemide had been given. On
      days 5- 8 blood was taken for determination of blood drug levels. On days 6-8
      blood samples were taken before and at 15, 30 and 45 min after tyramine
      administration for determination of plasma tyramine and plasma norepinephrine
      concentrations. When SBP had increased by approximately 30 mmHg no further doses
      of either intravenous or oral tyramine were given. Moclobemide was well tolerated
      by all subjects. Plasma trough levels of moclobemide were within the therapeutic
      range. The tyramine induced increases in SBP were greater during moclobemide than
      during placebo. After intravenous tyramine the dose-response curve for SBP was
      shifted to the right by a factor of approximately 3. When compared to placebo the
      pressor response to 100 mg tyramine orally was not significantly different, but
      the pressor response to the other two doses was enhanced during moclobemide.

PMID- 22156311
TI  - Ratio of serum n-3 to n-6 polyunsaturated fatty acids and the incidence of major
      adverse cardiac events in patients undergoing percutaneous coronary intervention.
AB  - BACKGROUND: The relationship between major adverse cardiac events (MACE) and
      serum polyunsaturated fatty acid (PUFA) parameters has not been well documented
      in patients who have undergone percutaneous coronary intervention (PCI). The aim
      of the present study was to investigate this relationship. METHODS AND RESULTS: A
      total of 284 consecutive patients who underwent elective PCI were enrolled and
      stratified according to median serum levels of n-6 PUFAs (arachidonic acid [AA]),
      n-3 PUFAs (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), and serum
      EPA/AA and DHA/AA ratios. The relationship between these PUFA parameters and the
      incidence of MACE including cardiac death, acute coronary syndrome, PCI for de
      novo lesions, and coronary artery bypass grafting, was analyzed. Multivariate
      analysis showed that among the PUFA parameters, only a high serum EPA/AA ratio
      was significantly associated with a low incidence of MACE in all the models
      tested (model A, without adjusted variables: hazard ratio [HR], 0.52; 95%
      confidence interval [CI]: 0.27-0.99, P = 0.048; model B, adjusted for age and
      diabetes: HR, 0.51; 95%CI: 0.26-0.98, P = 0.043; model C, adjusted for age, sex,
      diabetes, hypertension, smoking, and low-density lipoprotein cholesterol: HR,
      0.49; 95%CI: 0.25-0.94, P = 0.033). CONCLUSIONS: The incidence of MACE in
      patients who have undergone PCI is significantly associated with serum EPA/AA
      ratio.

PMID- 22156312
TI  - Gender-specific relationship between serum uric acid level and atrial
      fibrillation prevalence.
AB  - BACKGROUND: Although various kinds of cardiovascular risk factors have been
      reported to be associated with atrial fibrillation (AF), the relationship between
      serum uric acid level and AF has not been fully examined. METHODS AND RESULTS:
      Data were collected from a single hospital-based cohort in the Shinken Database
      2004-2008 (n=11,123), and consisted of serum uric acid level for 7,155 patients.
      The association between serum uric acid level and AF prevalence was evaluated on
      logistic regression. Uric acid significantly increased the crude AF prevalence in
      both men and women (both, P<0.001). The odds ratio (OR) and 95% confidence
      interval (95%CI) in the highest tertile compared with the lowest one were 3.368
      (2.478-4.578) and 1.408 (1.169-1.695) in women and men, respectively. Uric acid
      was also significantly associated with other various cardiovascular risk factors
      for AF. Even after the multivariate model was adjusted using these variables, the
      effect of uric acid on AF was independent in women (OR, 1.888; 95%CI: 1.278
      2.790), but not in men. CONCLUSIONS: Reflecting the composite of various
      cardiovascular risk factors, serum uric acid level was apparently associated with
      AF prevalence. The independent association in women might imply some sex-specific
      mechanisms. The results should be confirmed in prospective studies.

PMID- 22156313
TI  - Popcorn-like appearance of papillary fibroelastoma of the aortic valve -
      diagnosis on multimodality imaging; echocardiography, computed tomography and
      magnetic resonance imaging - .

PMID- 22156314
TI  - Randomized study on the efficacy and safety of landiolol, an ultra-short-acting
      beta1-adrenergic blocker, in patients with acute myocardial infarction undergoing
      primary percutaneous coronary intervention.
AB  - BACKGROUND: It is still controversial whether intravenous administration of beta
      blocker in the very acute phase of acute myocardial infarction (AMI) is
      beneficial. Landiolol is an ultra-short-acting beta-blocker that has less effect
      on blood pressure, but little is known about its efficacy and safety for patients
      with AMI undergoing primary percutaneous coronary intervention (PCI). METHODS AND
      RESULTS: A consecutive 96 patients with AMI not manifesting cardiogenic shock
      were prospectively randomized to landiolol (n = 47) or a control group (n = 49).
      Continuous administration of landiolol (3 ug.kg(-1).min(-1) for 24 h) was done
      just after PCI in the landiolol group, but not in the control group. Heart rate
      decreased by 9.4 +/- 1.7 beats/min after initiation of landiolol (P<0.01), but
      was unchanged in the control group. Left ventricular ejection fraction assessed 6
      months later was greater than that at 2 weeks in the landiolol group (52.0 +/-
      1.5 vs. 49.1 +/- 1.5%, P = 0.01), but remained unchanged in the control group.
      Left ventricular end-diastolic volume index assessed 6 months later was increased
      compared with that at 2 weeks in the control group (78.0 +/- 2.7 vs. 72.5 +/- 2.8
      ml/m(2), P = 0.02), whereas it was unchanged in the landiolol group. CONCLUSIONS:
      Early intravenous administration of landiolol in patients with AMI undergoing PCI
      is safe and has the potential to improve cardiac function and inhibit cardiac
      remodeling in the chronic phase.

PMID- 22156315
TI  - Coronary endothelial dysfunction and non-contrast multidetector computed
      tomography.

PMID- 22156316
TI  - Long-term risk of leukaemia or cardiomyopathy after mitoxantrone therapy for
      multiple sclerosis.
AB  - BACKGROUND: Mitoxantrone has been extensively used as a disease-modifying therapy
      for multiple sclerosis. However, estimates of the associated risk of therapy
      related acute leukaemia and cardiomyopathy have been derived from short-term
      studies. This study aimed to ascertain the long-term risk of therapy-related
      acute leukaemia or cardiomyopathy after mitoxantrone therapy for multiple
      sclerosis. METHODS: Between 2002 and 2010, 50 patients were treated with
      mitoxantrone at a single centre using a standard protocol (12 mg/m(2) body
      surface area monthly for 6 months as tolerated to a maximum of 72 mg/m(2) body
      surface area). Follow-up haematologic and echocardiographic data were collected
      in March 2011. RESULTS: Fifteen patients (30%) were excluded from analysis either
      because of lack of follow-up data, death due to non-cardiac and non-haematologic
      causes, or comorbid cardiovascular disease. The remaining 35 patients (70%) were
      followed for a median of 75 months (range: 9-103). The median cumulative
      mitoxantrone dose given was 72 mg/m(2) body surface area (range: 24-123). At the
      end of follow-up, no patients had developed therapy-related acute leukaemia. One
      patient suffered an asymptomatic drop in left ventricular ejection fraction from
      55 to 47%. CONCLUSION: This series of patients followed for up to 8.5 years
      suggests that the risk of either therapy-related acute leukaemia or
      cardiomyopathy after mitoxantrone therapy for multiple sclerosis is low when
      patients are treated within standard protocol.

PMID- 22156317
TI  - Difficulties in receiving a medical consultation among Japanese workers with
      mental health problems.
AB  - OBJECTIVES: The aim of this study was to elucidate the factors affecting the
      difficulties in receiving a medical consultation among workers with mental health
      problems. METHODS: The present study was performed using a cross-sectional
      survey. We requested occupational physicians and nurses who were members of the
      Japan Society for Occupational Health to distribute self-administered
      questionnaires to their clients. RESULTS: Ninety-nine workers (68 males and 30
      females), aged 40.6 +/- 9.1 yr, returned completed questionnaires; 65% of the
      respondents had been diagnosed with depression. The most common difficulty
      perceived by them was that there were no intra-office counselors. Multiple
      regression analysis revealed that the number of months between the onset of
      mental health problems and the first medical consultation was significantly
      associated with age and having no sick leave allowance. CONCLUSIONS: The
      implementation and enhancement of sick leave allowance may promote early
      intervention in regard to workplace mental health problems. Mental health
      education and regular checkups for older workers is also critical for early
      detection and intervention of mental health problems.

PMID- 22156318
TI  - Epidemiological study on risk factors for anxiety disorder among Chinese doctors.
AB  - OBJECTIVES: Anxiety disorders are the most prevalent mental health problem.
      However, few studies are available pertaining to this problem among Chinese
      doctors, a special occupational population exposed to high stress, especially
      during the implementation of health system reform. The aim of this study was to
      assess anxiety disorder among Chinese doctors and clarify its risk factors.
      METHODS: A cross-sectional study was conducted in 7 teaching hospitals of China
      Medical University. Questionnaires pertaining to anxiety disorder indicated by
      the Zung Self-Rating Anxiety Scale (SAS) and demographic characteristics, health
      status, lifestyle factors, work conditions and work-related psychological status
      were distributed to all registered doctors during April-June 2009. There were
      1,134 effective respondents (effective response rate 71.2%), and these
      respondents became our subjects (539 male doctors and 595 female doctors).
      RESULTS: The average standard scores of SAS for the male and female doctors were
      46.8 and 46.7. General linear model analysis indicated that SAS was associated
      with, in standardized estimate (beta) sequence, cynicism, emotional exhaustion,
      professional efficacy, sleeping problem, chronic diseases and physical exercise
      in men and with professional efficacy, emotional exhaustion, cynicism, sleeping
      problem, chronic diseases, job satisfaction, alcohol consumption and meals in
      women. Work-related psychological status contributed the most to the model R
      square. CONCLUSION: Chinese doctors were at considerably high risk of anxiety
      disorder and job burnout and sleeping problem had prominent roles. Interventions
      such as preventing exhaustion at work and improving sleep quality should be given
      attention during health care system reform with the aim of lessening anxiety
      disorder in doctors in China.

PMID- 22156319
TI  - Psychological and health impact of working with victims of sex trafficking.
AB  - OBJECTIVES: The UK is a major destination country for trafficking for sexual
      exploitation, and so increasing numbers of victims of trafficking are managed
      within health and social services. This study aims to assess the psychological
      and physical impact on health and social care staff working with an identified
      sex-trafficked population in a Northern City within England and identify methods
      to assist staff to manage this complex population. METHODS: This research is a
      qualitative study of 12 members of health and social care staff through semi
      structured interviews. The subjects were identified using purposive sampling, and
      data were analyzed using thematic analysis. RESULTS: Staff found working with sex
      trafficked populations more difficult than with other vulnerable groups. They
      frequently described burnout and other adverse effects on their psychological and
      physical health. In general, staff felt undersupported and undertrained by their
      organizations. This led to concerns about the quality and sustainability of the
      service. CONCLUSIONS: Working with victims of sex trafficking significantly
      impacts on the physical and psychological health of staff. Staff working with
      such vulnerable groups require training and high levels of support to ensure that
      they are not adversely affected by their work and to ensure that high quality
      services are maintained. Practices to promote occupational health must be
      instilled within workplace policy and the organizational culture to limit the
      impact on psychological and physical health in staff working with vulnerable
      populations.

PMID- 22156320
TI  - Workplace sexual harassment in two general hospitals in Taiwan: the incidence,
      perception, and gender differences.
AB  - OBJECTIVES: The aims of this study were to examine sexual harassment (SH) among
      hospital staffs in Taiwan, in terms of three-month incidence rate, the frequency
      of each type and the perception of SH, perpetrated by coworkers, patients and
      patients' families and to investigate the gender differences for these issues.
      METHODS: The subjects were employees at two general hospitals in Taiwan. The self
      administered "Hospital Sexual Harassment Questionnaire" was sent to eligible
      staff, and the voluntary respondents answered the questionnaire anonymously.
      There were 536 respondents available for analysis, with an overall response rate
      of 43.4%. RESULTS: The three-month incidence rates of SH by coworkers, patients,
      and patients' families in our study population were 2.4, 4.3, and 1.7%,
      respectively. Telling sexual jokes was the most common type of SH. The males had
      greater opportunities to be exposed to porn videos by their coworkers. The
      females were more frequently exposed to sex jokes and remarks made by patients
      and their family members and unwanted physical touching by patients in the
      workplace. There were significant differences with regard to the perception of
      sex jokes and sexually explicit verbal descriptions as SH or not between genders.
      CONCLUSIONS: The information in this study can be a helpful reference for
      administrators in hospitals when they are establishing education plans and
      policies. It might be possible to prevent sexual harassment and misunderstandings
      between genders and to further avoid the negative impact on the emotional well
      being of workers in hospitals.

PMID- 22156321
TI  - Maternal working hours and early childhood overweight in Japan: a population
      based study.
AB  - OBJECTIVES: There has been a growing concern that maternal employment could have
      adverse or beneficial effects on children's health. Although recent studies
      demonstrated that maternal employment was associated with a higher risk of
      childhood overweight, the evidence remains sparse in Asian countries. We sought
      to examine the relationship between maternal working hours and early childhood
      overweight in a rural town in Okayama Prefecture. METHODS: In February 2008,
      questionnaires were sent to parents of all preschool children aged >=3 yr in the
      town to assess maternal working status (working hours and form of employment),
      children's body mass index, and potential confounders. Childhood overweight was
      defined following the age and sex-specific criteria of the International Obesity
      Task Force. Odds ratios (ORs) and 95% confidence intervals (CIs) for childhood
      overweight were estimated in a logistic regression. We used generalized
      estimating equations with an exchangeable correlation matrix, considering the
      correlation between siblings. RESULTS: We analyzed 364 preschool children.
      Adjusting for each child's characteristics (age, sex), mother's characteristics
      (age, obesity, educational attainment, smoking status, and social participation),
      and family's characteristics (number of siblings), children whose mothers work <8
      h/day had a substantially lower risk for being overweight (OR: 0.28, 95% CI:
      0.09, 0.93) compared with children of non-working mothers, whereas the
      relationship was less pronounced among children whose mothers work >=8 h/day (OR:
      0.71, 95% CI: 0.19, 2.68). We observed similar patterns in a stratified analysis
      by the form of maternal employment. CONCLUSION: Short maternal working hours are
      associated with a lower odds of early childhood overweight.

PMID- 22156322
TI  - Visual display terminal use increases the prevalence and risk of work-related
      musculoskeletal disorders among Chinese office workers: a cross-sectional study.
AB  - OBJECTIVES: Little is known about work-related musculoskeletal disorders (WMSDs)
      among computer users mainland China. The aim of this study was to estimate the
      prevalence of WMSDs in office workers in Beijing, and to determine risk factors
      for WMSDs in the neck (WMSDs-N). METHODS: In a cross-sectional study, a self
      administered questionnaire was delivered to 720 office workers who use a computer
      as a main working tool. Odds ratios (ORs) were calculated for risk factors.
      RESULTS: The prevalence of WMSDs of the neck, shoulder, wrist/hand, upper back
      and low back amongst office workers were 55.5, 50.7, 31.5, 26.2 and 6.6%,
      respectively. Both individual risk factor and working condition factors were
      found to be independently related to WMSDs-N. CONCLUSIONS: The WMSDs prevalence
      rates among office workers in Beijing, China, were high. The most affected area
      was the neck. Preventive measures for office work should be focused on the neck
      (e.g., rest breaks).

PMID- 22156323
TI  - Inconsistencies in guidelines for visual health surveillance of VDT workers.
AB  - OBJECTIVES: In Europe, 25% of workers use video display terminals (VDTs).
      Occupational health surveillance has been considered a key element in the
      protection of these workers. Nevertheless, it is unclear if guidelines available
      for this purpose, based on EU standards and available evidence, meet currently
      accepted quality criteria. The aim of this study was to appraise three sets of
      European VDT guidelines (UK, France, Spain) in which regulatory and evidence
      based approaches for visual health have been formulated and recommendations for
      practice made. METHODS: Three independent appraisers used an adapted AGREE
      instrument with seven domains to appraise the guidelines. A modified nominal
      group technique approach was used in two consecutive phases: first, individual
      evaluation of the three guidelines simultaneously, and second, a face-to-face
      meeting of appraisers to discuss scoring. Analysis of ratings obtained in each
      domain and variability among appraisers was undertaken (correlation and kappa
      coefficients). RESULTS: All guidelines had low domain scores. The domain
      evaluated most highly was Scope and purpose, while Applicability was scored
      minimally. The UK guidelines had the highest overall score, and the Spanish ones
      had the lowest. The analysis of reliability and differences between scores in
      each domain showed a high level of agreement. CONCLUSIONS: These results suggest
      current guidelines used in these countries need an update. The formulation of
      evidence-base European guidelines on VDT could help to reduce the significant
      variation of national guidelines, which may have an impact on practical
      application.

PMID- 22156324
TI  - Baseline and stimulated cortisol levels in preterm infants: is there any clinical
      relevance?
AB  - BACKGROUND/AIM: To evaluate the association between the cortisol levels and
      clinical outcomes in preterm infants. METHODS: Baseline adrenocorticotropic
      hormone (ACTH) and cortisol levels and ACTH-stimulated cortisol concentrations
      after low-dose synthetic ACTH (Synacthen(r), 1 MUg/kg) were measured in preterm
      infants <37 weeks of gestational age between the 5th and 7th days of life.
      Associations between cortisol concentrations and clinical outcomes were examined.
      The prevalence and prognostic utility of relative adrenal insufficiency (AI) were
      assessed. RESULTS: Ninety-eight preterm infants were enrolled. Median baseline
      cortisol and ACTH levels were 13.7 MUg/dl (25th-75th percentile, 9.7-21.1 MUg/dl)
      and 11.5 pg/ml (25th-75th percentile, 6.9-22.6 pg/ml), respectively. Median peak
      cortisol level after ACTH stimulation was 33.6 MUg/dl (25th-75th percentile, 27.2
      40.2 MUg/dl). The prevalence of relative AI, defined as baseline cortisol <15
      MUg/dl or Delta-cortisol <9 MUg/dl, was 65%. Cortisol levels at baseline and at
      all time points during the test and relative AI were not associated with
      mortality or any other clinical outcomes. CONCLUSION: Neither baseline nor ACTH
      stimulated cortisol levels were associated with clinical outcomes in preterm
      infants. A significant proportion of preterm infants hospitalized in the neonatal
      unit fulfilled the criteria for relative AI; however, relative AI did not affect
      outcome.

PMID- 22156325
TI  - Effect of obesity on declining beta cell function after diagnosis of type 2
      diabetes: a possible link suggested by cross-sectional analysis.
AB  - It has been reported that beta cell function progressively declines in patients
      with type 2 diabetes.  The objective of this study was to assess the effect of
      obesity on declining beta cell function after diagnosis of type 2 diabetes.  We
      conducted a cross-sectional study of 689 consecutive subjects with type 2
      diabetes who were admitted to our hospital from 2000 to 2007.  Fasting and
      postprandial serum C-peptide immunoreactivity (CPR) and urinary CPR levels had
      been measured during admission.  The subjects were stratified according to BMI
      and time since diagnosis.  CPR index was calculated as CPR (ng/mL) / plasma
      glucose (mg/dL) x 100.  All CPR measurements were significantly higher in the 263
      obese (BMI >=25) subjects compared to the 426 lean subjects (BMI <25).  There was
      a significant negative correlation between CPR indices and duration of diabetes,
      suggesting a progressive decline in beta cell function after diagnosis of type 2
      diabetes.  However, this decline was more apparent in obese subjects
      (postprandial CPR index 0.059/year) compared to lean subjects (0.025/year).  The
      significant difference in serum CPR indices between the lean and obese subjects
      was lost in subjects more than 10 years after diagnosis.  In conclusion, our
      observations suggest that beta cell function shows a greater progressive decline
      in obese subjects than in lean subjects with type 2 diabetes.  Treatment of
      obesity may be an important strategy to preserve beta cell function in patients
      with type 2 diabetes.

PMID- 22156326
TI  - Second opinion in thyroid fine-needle aspiration biopsy by the Bethesda system.
AB  - The present study was designed to determine the impact of secondary review of
      thyroid fine-needle aspiration (FNA) biopsy on surgical management.  A
      retrospective review of patients referred to our institution with a thyroid FNA
      biopsy was conducted.  Cytologic diagnoses from the report at our center and the
      referring institution were re-categorized by the Bethesda System for Reporting
      Thyroid Cytopathology.  The rate of diagnostic disagreement was evaluated between
      Primary Diagnosis (PD) and Second Opinion Diagnosis (SOD), and the
      clinicopathologic correlations and the number of cases that prompted changes in
      treatment as a result of diagnostic disagreement were analyzed.  1499 patients
      meeting our study criteria were enrolled in this study.  Diagnostic disagreement
      comprised 394 cases (26.3%).  In the case of diagnostic disagreement, SOD was
      supported on clinicopathologic follow-up in 271 cases (68.8%), of which a change
      in management was made in 54 (13.7%) cases, and PD was supported in 93 (23.6%)
      cases, of which a change in management was made in 13 (3.3%) cases.  By the
      second opinion, 65 (4.5%) patients received proper management, and 14 (1.0%)
      patients received superfluous management.  Wide use of secondary cytopathologic
      review of thyroid FNA specimens from referring institutions was recommended.

PMID- 22156327
TI  - Long-term efficacy of sitagliptin for the treatment of type 2 diabetic patients
      in Japan.
AB  - We studied the efficacy of sitagliptin in type 2 diabetic patients of our
      outpatient clinics.  Since December in 2009, 164 patients have been treated by
      sitagliptin for their management of diabetes.  HbA1c decreased by 0.8% in all
      patients without any change in mean body weight after 3 months.  However,
      actually HbA1c did not decrease in 30 patients, and more than half of patients
      showed weight gain to some extent.  Patients were classified according to the
      reduction of HbA1c and analyzed based on this category.  Baseline characters such
      as age, gender, duration of diabetes, BMI, concomitantly used oral hypoglycemic
      agents and the score for life-style assessment were not related to glucose
      lowering effect of sitagliptin.  Ninety eight patients whose HbA1c had decreased
      after 3 months were further followed-up for another 3 months.  Among them 45
      patients showed some relapsing of HbA1c after 6 months, and they were compared
      with 53 patients without relapsing.  More cases had been switched from alpha
      glucosidase inhibitor (alpha-GI) and the score for life-style assessment was
      lower in relapsing patients compared to those in patients without relapsing.  In
      conclusion, clinicians should keep the fact in mind that the individual variation
      of glucose-lowering effects and the possibility of relapsing exist during
      sitagliptin treatment, and that concern about life-style is still a quite
      important issue to prevent weight gain and the relapsing of blood glucose
      control.

PMID- 22156328
TI  - Fusion imaging technology of the intracranial veins.
AB  - OBJECTIVES: Fusion imaging technology (FIT) combines different imaging techniques
      by means of properly designed software. The aim of this study was to validate the
      ultrasonographic representation of intracranial vein anatomy by combining
      transcranial echo-colour Doppler (TECD) with conventional magnetic resonance
      imaging (MRI). In addition, we investigated the possibility of insonating the
      veins of the base of the skull through the novel condylar window. METHODS: We
      examined venous brain circulation in five healthy subjects by means of FIT, using
      a 1.5 T MR scanner and an ultrasound TECD equipped with Virtual Navigator
      technology.  Results and conclusions Insonation of the Rosenthal and other
      intracranial veins through the classical transtemporal window, based on
      anatomical assumption, but never before validated by means of FIT study, was
      confirmed. Moreover, in all five subjects, FIT demonstrated the possibility of
      insonating the petrosal sinuses and the cavernous sinus area through the novel
      transcondylar approach. In conclusion, the feasibility of FIT of the intracranial
      veins potentially permits to study subjects in different postures and/or at the
      bed of non-transportable patients, after the initial MRI acquisition. Finally,
      the novel transcondylar approach allows obtaining haemodynamic information from
      the cavernous and the petrosal sinuses usually not investigated by TECD alone.

PMID- 22156329
TI  - Intravenous fluids cause systemic bias in a conductivity-based point-of-care
      hematocrit meter.
AB  - BACKGROUND: Point-of-care (POC) devices measuring hematocrit rely on
      determination of electrical conductivity of whole blood. We hypothesized that
      some frequently administered IV fluids independently alter blood conductivity and
      confound hematocrit determination. METHODS: Whole human blood was diluted to
      predetermined hematocrit values with normal saline, lactated Ringer solution,
      hetastarch, or plasma. Electrical conductivity and hematocrit (i-STAT(r) and spun
      methods) were measured at each dilution. In separate experiments, the effects of
      propofol and heparin were noted on these variables. RESULTS: Greater dilution
      significantly increased conductivity irrespective of diluent type. The magnitude
      of the conductivity slopes increased in order for plasma, hetastarch, lactated
      Ringer solution, and normal saline dilution. Moreover, each slope varied from
      every other slope (all P < 0.0001), and 94.2% of hematocrit values measured by i
      STAT (n = 211 of 224) were less than those for the spun method. Dilution with
      plasma, normal saline, lactated Ringer solution, and hetastarch caused bias
      (Bland-Altman limits of agreement) of -2.7% (-6.9/1.4), -4.6% (-7.3/-2.0), -4.8%
      (-7.8/-1.7), and -2.0% (-5.6/1.9), respectively. The Cohen kappa agreement values
      (5th-95th confidence interval) for a transfusion trigger of 30% were 0.90 (all
      values, 0.85-0.95), 0.25 (hematocrit <30%, 0.02-0.48), and 0.21 (hematocrit 18%
      30%, 0.01-0.42). Clinically relevant concentrations of propofol and heparin had
      minimal effects on electrical conductivity or hematocrit determination.
      CONCLUSIONS: Dilution of blood with frequently used IV solutions affects whole
      blood conductivity determinations and thereby decreases hematocrits measured by a
      POC device relying on this method as compared with spun hematocrit. Conductivity
      based hematocrit POC devices should be cautiously interpreted when hemodilution
      is present.

PMID- 22156330
TI  - R(+)-, Rac-, and S(-)-bupivacaine stereostructure-specifically interact with
      membrane lipids at cardiotoxically relevant concentrations.
AB  - It remains questionable whether local anesthetics can interact with membrane
      lipids at clinically relevant concentrations to show the difference between
      enantiomers. We compared the effects of bupivacaine stereoisomers on biomimetic
      membranes containing cardiolipin and cholesterol. Bupivacaine interacted with the
      membranes at cardiotoxic 5 MUM with the potency being S(-)-enantiomer < racemate
      < R(+)-enantiomer, which agreed with the rank order of their cardiotoxicity. Such
      differences became greater with decreasing drug concentrations, possibly
      explaining the inconsistent cardiotoxic potencies of bupivacaine stereoisomers
      reported previously. The interactivity with biomembranes may in part contribute
      to the mode of toxic action of local anesthetics.

PMID- 22156331
TI  - Propofol protects against high glucose-induced endothelial dysfunction in human
      umbilical vein endothelial cells.
AB  - BACKGROUND: Hyperglycemia, via peroxynitrite-mediated endothelial nitric oxide
      synthase (eNOS) enzymatic uncoupling, induced endothelial dysfunction. Propofol
      has been reported to improve high glucose-induced endothelial dysfunction.
      However, its mechanisms of action remain unclear. We hypothesized that propofol
      could improve hyperglycemia-induced endothelial dysfunction by decreasing the
      peroxynitrite level and thus restoring eNOS coupling. METHODS: At the end of 3
      days of incubation in medium with 30 mM glucose, human umbilical vein endothelial
      cells were treated with different concentrations (0.2, 1, 5, and 25 MUM) of
      propofol for different times (0.5, 1, 2, and 4 hours). In parallel experiments,
      cells were cultured in 5 mM glucose for 3 days as a control. Nitric oxide (NO)
      production was measured with a nitrate reductase assay. Superoxide anion (O(2)(.
      )) accumulation was measured with the reduction of ferricytochrome c and
      dihydroethidine fluorescence assay. The treatment that had maximal effect on 30
      mM glucose-induced NO production and O(2)(.-) accumulation was applied in the
      following studies to examine the underlying signaling pathways. eNOS total
      protein, eNOS dimer and monomer expression, eNOS phosphorylation at Ser(1177),
      inducible NO synthase total protein, inducible NO synthase dimer and monomer
      expression, peroxynitrite, and guanosine triphosphate cyclohydrolase I expression
      were measured by Western blot. Tetrahydrobiopterin (BH(4)) level was measured
      with liquid chromatography-mass spectrometry. RESULTS: Compared with 5 mM glucose
      treatment, 30 mM glucose significantly decreased NO production by 60% (P < 0.001)
      and increased O(2)(.-) accumulation by 175% (P = 0.0026), which were both
      attenuated by propofol in a concentration- and time-dependent manner. Compared
      with 5 mM glucose treatment, total eNOS protein expression was increased by 30 mM
      glucose (P < 0.001), whereas the ratio of eNOS dimer/monomer (P = 0.0001) and
      eNOS phosphorylation (P < 0.001) were decreased by 30 mM glucose. Propofol did
      not affect 30 mM glucose-induced total eNOS protein expression, but restored the
      ratio of eNOS dimer/monomer (P = 0.0005) and increased eNOS phosphorylation (P <
      0.001). 30 mM glucose-induced O(2)(.-) accumulation was inhibited by the eNOS
      inhibitor hydrochloride. Furthermore, compared with 5 mM glucose treatment, 30 mM
      glucose decreased the BH(4) level (P = 0.0001) and guanosine triphosphate
      cyclohydrolase I expression (P < 0.001), whereas it increased peroxynitrite level
      (P = 0.0003), which could all be reversed by propofol (P = 0.0045, P < 0.001, P =
      0.0001 vs 30 mM glucose treatment, respectively). CONCLUSIONS: Propofol has
      beneficial effects on 30 mM glucose-induced NO reduction and O(2)(.-)
      accumulation in human umbilical vein endothelial cells. This may be mediated
      through inhibiting peroxynitrite-mediated BH(4) reduction, and restoring eNOS
      coupling.

PMID- 22156332
TI  - Cerebrospinal fluid neurotransmitter changes during the perioperative period in
      patients undergoing total knee replacement: a randomized trial.
AB  - BACKGROUND: Total knee replacement (TKR) is of enormous benefit to patients with
      osteoarthritis of the knee; however, the acute postoperative pain can be severe
      and difficult to manage. The role of major spinal cord neurotransmitters in this
      acute postoperative period is not clear, although there are a few studies in
      humans. We performed the first prospective clinical study undertaken to delineate
      the changes in the spinal neurotransmitters after a surgery such as TKR.
      Furthermore, we also determined whether antihyperalgesic drugs at clinically
      acceptable doses modulate spinal neurotransmitter concentrations in patients
      during the perioperative period. METHODS: All patients had a spinal needle placed
      in the lumbar region and cerebrospinal fluid (CSF) obtained for baseline
      measurement of the neurotransmitters. An intrathecal catheter was then placed for
      spinal anesthesia for standard TKR and for continuous spinal postoperative
      analgesia. The spinal catheter was also used postoperatively to sample CSF at 2,
      4, 8, 12, 24, and 32 hours after catheter placement. CSF samples were assayed for
      norepinephrine, substance P, calcitonin gene-related peptide (CGRP), and
      glutamate concentrations. SF-36 (36-item Short Form Health Survey) was measured
      preoperatively. Numerical rating scale (NRS) pain scores and intrathecal
      analgesic consumption were recorded postsurgery at 4-hour intervals for 32 hours.
      We performed a randomized, placebo-controlled, double-blind trial with 3 drug
      groups (n = 16 per group): placebo; single-dose pregabalin (150 mg administered
      before surgery); and multidose pregabalin (150 mg administered presurgery and 12
      and 24 hours later), to determine the effect of an antihyperalgesic drug such as
      pregabalin on spinal neurotransmitters. RESULTS: Forty-eight patients were
      randomly assigned to the 3 perioperative treatment groups, and multiple CSF
      samples were successfully obtained from 44 patients. Before surgery, increased
      bodily pain (from preoperative SF-36 measure) was correlated with increased CSF
      norepinephrine concentration (P = 0.044). Compared with presurgery values,
      norepinephrine levels were lower in the placebo group at the 2- and 4-hour time
      points (P < 0.005) whereas in the single and multidose groups, the reduction (P <
      0.001) continued until 12 and 24 hours, respectively. Substance P CSF levels had
      an early peak value (at 2 hours) in all 3 groups, and then returned to baseline.
      Compared with baseline value, the CGRP CSF levels only decreased at the 32-hour
      time point in the placebo group, but in both pregabalin groups, CGRP levels
      decreased over the 4- to 32-hour period. In the placebo group only, CSF glutamate
      decreased over 4 to 32 hours compared with presurgery values. However, there was
      no difference in the CSF neurotransmitter concentrations among the 3 treatment
      groups over the 32-hour sampling period. In the placebo group, the early NRS pain
      score area under the curve, AUC [0-12 hours], was positively correlated (R =
      0.67, P = 0.0088) with the CSF norepinephrine concentration AUC [12-24 hours],
      but none of the other neurotransmitters was correlated with the NRS. None of the
      CSF neurotransmitter concentrations correlated with postoperative analgesic
      consumption. CONCLUSION: In the perioperative period, the concentration changes
      of the 4 spinal neurotransmitters have a distinct time course. CSF substance P
      seems to increase very rapidly with surgical intervention, whereas the CSF
      norepinephrine concentration tends to decrease. At clinical doses, pregabalin
      does not seem to modulate these spinal neurotransmitter concentrations.

PMID- 22156333
TI  - The efficacy of intravenous patient-controlled analgesia after intracranial
      surgery of the posterior fossa: a prospective, randomized controlled trial.
AB  - BACKGROUND: Surgery of the posterior fossa often produces intense postoperative
      pain. However, this pain is infrequently treated because of concern that opioid
      administration may mask the postoperative neurologic examination and/or produce
      hypercarbia. In this prospective, randomized controlled trial, we sought to
      determine whether IV patient-controlled analgesia (PCA) would lead to reductions
      in postoperative pain after neurosurgical procedures of the posterior fossa
      compared with conventional IV nurse-administered as-needed (PRN) therapy.
      METHODS: Eighty patients (age range, 18-82 years) undergoing elective posterior
      fossa surgery were randomized to receive postoperative IV fentanyl PRN 25 to 50
      MUg every 30 minutes or via PCA 0.5 MUg/kg/dose, with a maximal dose limit of 50
      MUg, and 15-minute lockout (4 doses/hour). We measured pain (Numerical Rating
      Scale, 0-10), analgesic use, sedation (Ramsay Sedation Scale and Glasgow Coma
      Scale), respiration, hemodynamics, and adverse events hourly. RESULTS: Sixty-five
      patients completed the study. Thirty-one patients received IV PCA and 34 received
      PRN analgesia. Patient demographics did not differ between groups. Patients in
      the PCA group reported less pain at rest (mean [95% confidence interval]: 3.7
      [3.0, 4.4] vs 5.2 [4.5, 5.8], P = 0.003) and received more fentanyl (mean [95%
      confidence interval]: 54.8 [42.1, 67.6] vs 29.9 [24.2, 35.7] MUg/h, P = 0.002)
      than those in the PRN group. There were no differences in side effects and no
      adverse events related to analgesic therapy. CONCLUSIONS: IV PCA use resulted in
      reduction in postoperative pain compared with PRN analgesic therapy after surgery
      of the posterior fossa. Larger studies will be required to determine the safety
      of IV PCA in this patient population.

PMID- 22156334
TI  - The role of perioperative high inspired oxygen therapy in reducing surgical site
      infection: a meta-analysis.
AB  - BACKGROUND: The clinical role of hyperoxia for preventing surgical site infection
      remains uncertain because randomized controlled trials on this topic have
      reported disparate results. Our objective in this systematic review was to
      determine whether perioperative hyperoxia reduces surgical site infection.
      METHODS: An electronic search was conducted using the National Library of
      Medicine's MEDLINE, Cochrane Collaboration's CENTRAL, and EMBASE databases.
      Included studies consisted of randomized controlled trials in an adult population
      with a clearly defined comparison of high oxygen versus low oxygen or control,
      and with a documented assessment for perioperative infection. Pooled estimates
      for odds ratios (ORs) with 95% confidence intervals were obtained for our primary
      outcome (surgical site infection) using the Cochrane Collaboration's RevMan
      version 5.0.25 (Cochrane Collaboration, Oxford, UK). ORs were calculated using a
      random effects model. RESULTS: The literature search ultimately yielded 7 trials,
      enrolling 2728 patients, that were included in the analysis. There were 1358
      patients randomly assigned to hyperoxia and 1370 to control. The pooled infection
      rate in the hyperoxia group was 15.5% versus 17.5% in the control group.
      Hyperoxia resulted in an OR of 0.85 for surgical site infection (95% confidence
      interval: 0.52, 1.38) (P = 0.51). However, 2 subgroup analyses (general
      anesthesia and colorectal surgery trials) showed a benefit for high inspired
      oxygen therapy of decreasing surgical site infection. CONCLUSIONS: Perioperative
      high inspired oxygen therapy overall was not found to be beneficial for
      preventing surgical site infection based on this meta-analysis. The positive
      results of 2 subgroup analyses (general anesthesia and colorectal surgery trials)
      suggest a benefit for hyperoxia in decreasing surgical site infection. Additional
      studies are needed to further investigate this intervention.

PMID- 22156335
TI  - The diagnostic value of controlled oral word association test-FAS and category
      fluency in single-domain amnestic mild cognitive impairment.
AB  - BACKGROUND: Recent studies have shown that decreases in both letter fluency and
      category fluency may be present in addition to memory impairment in single-domain
      amnestic mild cognitive impairment (aMCI). However, the clinical utility of these
      fluency measures is unclear. The aim of this study was to determine what, if any,
      diagnostic value letter and category fluency provide in differentiating single
      domain aMCI from normal cognition. METHODS: Data from 66 individuals [33
      cognitively normal (CN) and 33 aMCI] between the ages of 66 and 87 years
      participating in the Florida Alzheimer's Disease Research Center were compared on
      the Controlled Oral Word Association Test (COWAT)-FAS and Category Fluency test,
      both in terms of raw and scaled scores. RESULTS: Participants were matched on
      age, education and sex. Two-tailed independent sample t-tests found statistically
      significant differences between the CN and aMCI groups for both raw and scaled
      scores of COWAT-FAS and Category Fluency (p < 0.001). Logistic regression
      analyses found that COWAT-FAS and Category Fluency did not significantly improve
      diagnostic accuracy when combined with the Hopkins Verbal Learning Test-Revised
      delayed recall. CONCLUSION: Although decreased COWAT-FAS and Category Fluency
      performance may be present in single-domain aMCI, these tests do not improve the
      ability of the Hopkins Verbal Learning Test-Revised delayed recall to
      differentiate aMCI from CN individuals.

PMID- 22156336
TI  - Development of Parkinson and Alzheimer diseases in two cases of narcolepsy
      cataplexy.

PMID- 22156337
TI  - Cellular prion protein mediates toxic signaling of amyloid beta.
AB  - Prion diseases in humans and animals comprise a group of invariably fatal
      neurodegenerative diseases characterized by the formation of a pathogenic protein
      conformer designated PrP(Sc) and infectious particles denoted prions. The
      cellular prion protein (PrP(C)) has a central role in the pathogenesis of prion
      disease. First, it is the precursor of PrP(Sc) and infectious prions and second,
      its expression on neuronal cells is required to mediate toxic effects of prions.
      To specifically study the role of PrP(C) as a mediator of toxic signaling, we
      have developed novel cell culture models, including primary neurons prepared from
      PrP-deficient mice. Using these approaches we have been able to show that PrP(C)
      can interact with and mediate toxic signaling of various beta-sheet-rich
      conformers of different origins, including amyloid beta, suggesting a
      pathophysiological role of the prion protein beyond prion diseases.

PMID- 22156338
TI  - The proapoptotic Bcl-2 family member Bim plays a central role during the
      development of virus-induced hepatitis.
AB  - The proapoptotic Bcl-2 homolog Bim was shown to control the apoptosis of both T
      cells and hepatocytes. This dual role of Bim might be particularly relevant for
      the development of viral hepatitis, in which both the sensitivity of hepatocytes
      to apoptosis stimuli and the persistence of cytotoxic T cells are essential
      factors for the outcome of the disease. The relevance of Bim in regulating
      survival of cytotoxic T cells or induction of hepatocyte death has only been
      investigated in separate systems, and their relative contributions to the
      pathogenesis of T cell-mediated hepatitis remain unclear. Using the highly
      dynamic model system of lymphocytic choriomeningitis virus-mediated hepatitis and
      bone marrow chimeras, we found that Bim has a dual role in the development of
      lymphocytic choriomeningitis virus-induced, T cell-mediated hepatitis. Although
      the absence of Bim in parenchymal cells led to markedly attenuated liver damage,
      loss of Bim in the lymphoid compartment moderately enhanced hepatitis. However,
      when both effects were combined in Bim(-/-) mice, the effect of Bim deficiency in
      the lymphoid compartment was overcompensated for by the reduced sensitivity of
      Bim(-/-) hepatocytes to T cell-induced apoptosis, resulting in the protection of
      Bim(-/-) mice from hepatitis.

PMID- 22156339
TI  - Granzyme H of cytotoxic lymphocytes is required for clearance of the hepatitis B
      virus through cleavage of the hepatitis B virus X protein.
AB  - The granule exocytosis pathway of cytotoxic lymphocytes plays critical roles in
      eradication of intracellular viruses. However, how hepatitis B virus (HBV) is
      cleared has not been defined. To clarify immune mechanisms underlying inhibition
      of the HBV replication, the relationship between granzyme H (GzmH) and HBV
      clearance was investigated. In this study, we found that the granule exocytosis
      pathway can inhibit HBV replication without induction of cytolysis of the
      infected cells. GzmH is essential for HBV eradication. The HBx protein (HBx),
      required for the replication of HBV, is cleaved at Met(79) by GzmH. GzmH
      inhibitor can abolish GzmH- and lymphokine-activated killer cell-mediated HBx
      degradation and HBV clearance. An HBx-deficient HBV is resistant to GzmH- and
      lymphokine-activated killer cell-mediated viral clearance. Adoptive transfer of
      GzmH-overexpressing NK cells into HBV carrier mice facilitates in vivo HBV
      eradication. Importantly, low GzmH expression in cytotoxic lymphocytes of
      individuals is susceptible to HBV infection and hepatocellular carcinoma. These
      results indicate that GzmH might be detected as a potential parameter for
      diagnosis of HBV infection and hepatocellular carcinoma.

PMID- 22156340
TI  - Size-dependent attenuation of TLR9 signaling by gold nanoparticles in
      macrophages.
AB  - Gold nanoparticles (GNPs), which are generally thought to be bio-inert and non
      cytotoxic, have become one of the most ideal nanomaterials for medical
      applications. Once engulfed by phagocytes, the immunological effects of GNPs are
      still of concern and require detailed investigation. Therefore, this study
      explored the immunological significance of GNPs on TLR-mediated innate immunity
      in murine macrophages. GNP causes specific inhibition of TLR9 (CpG
      oligodeoxynucleotides; CpG-ODNs) signal in macrophages. The impaired CpG-ODN
      induced TNF-alpha production is GNP concentration- and size-dependent in murine
      Raw264.7 cells: a GNP of 4 nm in size is more potent than a GNP of 11, 19, 35, or
      45 nm in size. Consistent with cytokine inhibition, the CpG-ODN-induced
      phosphorylation of NF-kappaB and JNK as well as NF-kappaB activation are
      suppressed by GNPs. GNPs accumulate in lysosomes after phagocytosis and also
      increase TLR9-associated lysosomal cathepsin expression and activities, but this
      is irrelevant to TLR9 inhibition by GNPs in our studies. In addition, GNPs
      affected TLR9 translocation in response to CpG-ODNs and to phagosomes. Further
      exploring how GNPs inhibited TLR9 function, we found that GNPs could bind to high
      mobility group box-1 (which is involved in the regulation of TLR9 signaling)
      inside the lysosomes. The current studies demonstrate that size-dependent
      inhibition of TLR9 function by GNP may be attributed to its binding to high
      mobility group box-1.

PMID- 22156341
TI  - Rapid in vivo conversion of effector T cells into Th2 cells during helminth
      infection.
AB  - Stimulation of the immune system by pathogens, allergens, or autoantigens leads
      to differentiation of CD4(+) T cells with pro- or anti-inflammatory effector cell
      functions. Based on functional properties and expression of characteristic
      cytokines and transcription factors, effector CD4(+) T cells have been grouped
      mainly into Th1, Th2, Th17, and regulatory T (Treg) cells. At least some of these
      T cell subsets remain responsive to external cues and acquire properties of other
      subsets, raising the hope that this functional plasticity might be exploited for
      therapeutic purposes. In this study, we used an Ag-specific adoptive transfer
      model and determined whether in vitro-polarized or ex vivo-isolated Th1, Th17, or
      Treg cells can be converted into IL-4-expressing Th2 cells in vivo by infection
      of mice with the gastrointestinal helminth Nippostrongylus brasiliensis. Th1 and
      Th17 cells could be repolarized to acquire the expression of IL-4 and lose the
      expression of their characteristic cytokines IFN-gamma and IL-17A, respectively.
      In contrast, both in vitro-generated and ex vivo-isolated Treg cells were largely
      resistant to repolarization. The helminth-induced conversion of Th1 or Th17 cells
      into Th2 cells may partially explain the inverse correlation between helminth
      infection and protection against autoimmune disorders.

PMID- 22156342
TI  - The nature of an in vivo anti-capsular polysaccharide response is markedly
      influenced by the composition and/or architecture of the bacterial subcapsular
      domain.
AB  - In vivo anti-polysaccharide Ig responses to isolated polysaccharide (PS) are T
      cell independent, rapid, and fail to generate memory. However, little is known
      regarding PS-specific Ig responses to intact gram-positive and gram-negative
      extracellular bacteria. We previously demonstrated that intact heat-killed
      Streptococcus pneumoniae, a gram-positive bacterium, elicited a rapid primary
      pneumococcal capsular PS (PPS) response in mice that was dependent on CD4(+) T
      cells, B7-dependent costimulation, and CD40-CD40L interactions. However, this
      response was ICOS independent and failed to generate a boosted PPS-specific
      secondary IgG response. In the current study, we analyzed the murine
      meningococcal type C PS (MCPS)-specific Ig response to i.p.-injected intact, heat
      killed Neisseria meningitidis, serogroup C (MenC), a gram-negative bacterium. In
      contrast to S. pneumoniae, the IgG anti-MCPS response to MenC exhibited delayed
      primary kinetics and was highly boosted after secondary immunization, whereas the
      IgG anti-MCPS response to isolated MCPS was rapid, without secondary boosting,
      and consisted of only IgG1 and IgG3, as opposed to all four IgG isotypes in
      response to intact MenC. The secondary, but not primary, IgG anti-MCPS response
      to MenC was dependent on CD4(+) T cells, CD40L, CD28, and ICOS. The primary and
      secondary IgG anti-MCPS responses were lower in TLR4-defective (C3H/HeJ) but not
      TLR2(-/-) or MyD88(-/-) mice, but secondary boosting was still observed. Of
      interest, coimmunization of S. pneumoniae and MenC resulted in a boosted
      secondary IgG anti-PPS response to S. pneumoniae. Our data demonstrate that the
      nature of the in vivo anti-PS response is markedly influenced by the composition
      and/or architecture of the bacterial subcapsular domain.

PMID- 22156344
TI  - Regulation of the inflammatory response: enhancing neutrophil infiltration under
      chronic inflammatory conditions.
AB  - Neutrophil (polymorphonuclear leukocytes [PMN]) infiltration plays a central role
      in inflammation and is also a major cause of tissue damage. Thus, PMN
      infiltration must be tightly controlled. Using zymosan-induced peritonitis as an
      in vivo PMN infiltration model, we show in this study that PMN response and
      infiltration were significantly enhanced in mice experiencing various types of
      systemic inflammation, including colitis and diabetes. Adoptive transfer of
      leukocytes from mice with inflammation into healthy recipients or from healthy
      into inflammatory recipients followed by inducing peritonitis demonstrated that
      both circulating PMN and tissue macrophages were altered under inflammatory
      conditions and that they collectively contributed to enhanced PMN infiltration.
      Detailed analyses of dextran sulfate sodium-elicited colitis revealed that
      enhancement of PMN infiltration and macrophage function occurred only at the
      postacute/chronic phase of inflammation and was associated with markedly
      increased IL-17A in serum. In vitro and ex vivo treatment of isolated PMN and
      macrophages confirmed that IL-17A directly modulates these cells and
      significantly enhances their inflammatory responses. Neutralization of IL-17A
      eliminated the enhancement of PMN infiltration and IL-6 production and also
      prevented severe tissue damage in dextran sulfate sodium-treated mice. Thus, IL
      17A produced at the chronic stage of colitis serves as an essential feedback
      signal that enhances PMN infiltration and promotes inflammation.

PMID- 22156343
TI  - Adiponectin attenuates lipopolysaccharide-induced acute lung injury through
      suppression of endothelial cell activation.
AB  - Adiponectin (APN) is an adipose tissue-derived factor with anti-inflammatory and
      vascular protective properties whose levels paradoxically decrease with
      increasing body fat. In this study, APN's role in the early development of ALI to
      LPS was investigated. Intratracheal LPS elicited an exaggerated systemic
      inflammatory response in APN-deficient (APN(-/-)) mice compared with wild-type
      (wt) littermates. Increased lung injury and inflammation were observed in APN(-/
      ) mice as early as 4 h after delivery of LPS. Targeted gene expression profiling
      performed on immune and endothelial cells isolated from lung digests 4 h after
      LPS administration showed increased proinflammatory gene expression (e.g., IL-6)
      only in endothelial cells of APN(-/-) mice when compared with wt mice. Direct
      effects on lung endothelium were demonstrated by APN's ability to inhibit LPS
      induced IL-6 production in primary human endothelial cells in culture.
      Furthermore, T-cadherin-deficient mice that have significantly reduced lung
      airspace APN but high serum APN levels had pulmonary inflammatory responses after
      intratracheal LPS that were similar to those of wt mice. These findings indicate
      the importance of serum APN in modulating LPS-induced ALI and suggest that
      conditions leading to hypoadiponectinemia (e.g., obesity) predispose to
      development of ALI through exaggerated inflammatory response in pulmonary
      vascular endothelium.

PMID- 22156345
TI  - Leukocyte-associated Ig-like receptor-1-deficient mice have an altered immune
      cell phenotype.
AB  - Cross-linking of the collagen binding receptor leukocyte-associated Ig-like
      receptor-1 (LAIR-1) in vitro delivers an inhibitory signal that is able to
      downregulate activation-mediated signals. To study the in vivo function of LAIR
      1, we generated LAIR-1(-/-) mice. They are healthy and fertile and have normal
      longevity; however, they show certain phenotypic characteristics distinct from
      wild-type mice, including increased numbers of splenic B, regulatory T, and
      dendritic cells. As LAIR-1(-/-) mice age, the splenic T cell population shows a
      higher frequency of activated and memory T cells. Because LAIR-1(+/+) and LAIR-1(
      /-) T cells traffic with equal proficiency to peripheral lymphoid organs, this is
      not likely due to abnormal T lymphocyte trafficking. LAIR-1(-/-) mice have lower
      serum levels of IgG1 and, in response to T-dependent immunization with
      trinitrophenyl-OVA, switch less efficiently to Ag specific IgG2a and IgG2b,
      whereas switching to IgG1 is not affected. Several mouse disease models,
      including experimental autoimmune encephalitis and colitis, were used to examine
      the effect of LAIR-1 deficiency, and no differences in the responses of LAIR-1(-/
      ) and LAIR-1(+/+) mice were observed. Taken together, these observations indicate
      that LAIR-1 plays a role in regulating immune cells and suggest that any adverse
      effects of its absence may be balanced in vivo by other inhibitory receptors.

PMID- 22156347
TI  - Trogocytosis is a gateway to characterize functional diversity in melanoma
      specific CD8+ T cell clones.
AB  - Trogocytosis, the transfer of membrane patches from target to immune effector
      cells, is a signature of tumor-T cell interaction. In this study, we used the
      trogocytosis phenomenon to study functional diversity within tumor-specific T
      cell clones with identical TCR specificity. MART-1(26-35)-specific CD8 T cell
      clones, which differed in their trogocytosis capacity (low [2D11], intermediate
      [2G1], high [2E2]), were generated from melanoma patients. Functional evaluation
      of the clones showed that the percentage of trogocytosis-capable T cells closely
      paralleled each clone's IFN-gamma and TNF-alpha production, lysosome
      degranulation, and lysis of peptide-pulsed targets and unmodified melanoma. The
      highly cytotoxic 2E2 clone displayed the highest TCR peptide binding affinity,
      whereas the low-activity 2D11 clone showed TCR binding to peptide-MHC in a CD8
      dependent manner. TCR analysis revealed Vbeta16 for clones 2E2 and 2G1 and
      Vbeta14 for 2D11. When peptide-affinity differences were bypassed by nonspecific
      TCR stimulation, clones 2E2 and 2D11 still manifested distinctive signaling
      patterns. The high-activity 2E2 clone displayed prolonged phosphorylation of
      ribosomal protein S6, an integrator of MAPK and AKT activation, whereas the low
      activity 2D11 clone generated shorter and weaker phosphorylation. Screening the
      two clones with identical TCR Vbeta by immunoreceptor array showed higher
      phosphorylation of NK, T, and B cell Ag (NTB-A), a SLAM family homophilic
      receptor, in clone 2E2 compared with 2G1. Specific blocking of NTB-A on APCs
      markedly reduced cytokine production by CD8 lymphocytes, pointing to a possible
      contribution of NTB-A costimulation to T cell functional diversity. This finding
      identifies NTB-A as a potential target for improving anti-cancer immunotherapy.

PMID- 22156346
TI  - Mice with mutations in Fas and Fas ligand demonstrate increased herpetic stromal
      keratitis following corneal infection with HSV-1.
AB  - HSV-1 infection of the cornea leads to a potentially blinding immunoinflammatory
      lesion of the cornea, termed herpetic stromal keratitis. It has also been shown
      that one of the factors limiting inflammation of the cornea is the presence of
      Fas ligand (FasL) on corneal epithelium and endothelium. In this study, the role
      played by FasL expression in the cornea following acute infection with HSV-1 was
      determined. Both BALB/c and C57BL/6 (B6) mice with HSV-1 infection were compared
      with their lpr and gld counterparts. Results indicated that mice bearing
      mutations in the Fas Ag (lpr) displayed the most severe disease, whereas the FasL
      defective gld mouse displayed an intermediate phenotype. It was further
      demonstrated that increased disease was due to lack of Fas expression on bone
      marrow-derived cells. Of interest, although virus persisted slightly longer in
      the corneas of mice bearing lpr and gld mutations, the persistence of infectious
      virus in the trigeminal ganglia was the same for all strains infected. Further,
      B6 mice bearing lpr and gld mutations were also more resistant to virus-induced
      mortality than were wild-type B6 mice. Thus, neither disease nor mortality
      correlated with viral replication in these mice. Collectively, the findings
      indicate that the presence of FasL on the cornea restricts the entry of Fas(+)
      bone marrow-derived inflammatory cells and thus reduces the severity of HSK.

PMID- 22156348
TI  - IL-27 enhances LPS-induced proinflammatory cytokine production via upregulation
      of TLR4 expression and signaling in human monocytes.
AB  - IL-27, which is produced by activated APCs, bridges innate and adaptive immunity
      by regulating the development of Th cells. Recent evidence supports a role for IL
      27 in the activation of monocytic cells in terms of inflammatory responses.
      Indeed, proinflammatory and anti-inflammatory activities are attributed to IL-27,
      and IL-27 production itself is modulated by inflammatory agents such as LPS. IL
      27 primes LPS responses in monocytes; however, the molecular mechanism behind
      this phenomenon is not understood. In this study, we demonstrate that IL-27
      priming results in enhanced LPS-induced IL-6, TNF-alpha, MIP-1alpha, and MIP
      1beta expression in human primary monocytes. To elucidate the molecular
      mechanisms responsible for IL-27 priming, we measured levels of CD14 and TLR4
      required for LPS binding. We determined that IL-27 upregulates TLR4 in a STAT3-
      and NF-kappaB-dependent manner. Immunofluorescence microscopy revealed enhanced
      membrane expression of TLR4 and more distinct colocalization of CD14 and TLR4
      upon IL-27 priming. Furthermore, IL-27 priming enhanced LPS-induced activation of
      NF-kappaB family members. To our knowledge, this study is the first to show a
      role for IL-27 in regulating TLR4 expression and function. This work is
      significant as it reveals new mechanisms by which IL-27 can enhance
      proinflammatory responses that can occur during bacterial infections.

PMID- 22156349
TI  - Type I IFN-dependent T cell activation is mediated by IFN-dependent dendritic
      cell OX40 ligand expression and is independent of T cell IFNR expression.
AB  - Type I IFNs are important for direct control of viral infection and generation of
      adaptive immune responses. Recently, direct stimulation of CD4(+) T cells via
      type I IFNR has been shown to be necessary for the formation of functional CD4(+)
      T cell responses. In contrast, we find that CD4(+) T cells do not require
      intrinsic type I IFN signals in response to combined TLR/anti-CD40 vaccination.
      Rather, the CD4 response is dependent on the expression of type I IFNR
      (IFNalphaR) on innate cells. Further, we find that dendritic cell (DC) expression
      of the TNF superfamily member OX40 ligand was dependent on type I IFN signaling
      in the DC, resulting in a reduced CD4(+) T cell response that could be
      substantially rescued by an agonistic Ab to the receptor OX40. Taken together, we
      show that the IFNalphaR dependence of the CD4(+) T cell response is accounted for
      exclusively by defects in DC activation.

PMID- 22156350
TI  - Anti-free radical effects of dark chocolate in radical damage and constipation.

PMID- 22156351
TI  - Human beta-defensin 2 concentration of respiratory tract mucosa in elderly
      patients with pneumonia and its associated factors.
AB  - AIM: to identify HBD2 peptide in sputum of patients with pneumonia; to obtain
      mean concentration difference of HBD2 between elderly patients and the younger
      adults with pneumonia; and to find any association between age, nutritional
      status, smoking habits, diabetes mellitus, and chronic obstructive pulmonary
      disease (COPD) and the concentration of HBD2 in patients with pneumonia. METHODS:
      a cross-sectional study with consecutive sampling technique was conducted in 23
      elderly patients and 38 younger adults with pneumonia who were hospitalized in
      Cipto Mangunkusumo Hospital, Jakarta. Patients with pulmonary and respiratory
      tract malignancy, taking long-term corticosteroid and/or immunosuppressant
      therapy were excluded. The sputum of patient was taken spontaneously or by sputum
      induction technique and prepared for identification by dissolving with
      dithiothreitol (DTT) solution. The presence of HBD2 was identified by using SDS
      PAGE and immunoblotting; while the concentration was measured by ELISA. The mean
      difference of HBD2 concentrations between elderly patients and the young adults
      was analyzed using t-test. Chi-square test was performed to analyze the
      association between several risk factors and HBD2 concentrations in the sputum.
      RESULTS: the mean concentration of HBD2 in the sputum of all subjects was 178.98
      (SD 49.55) pg/ml. There was no mean concentration difference of HBD2 between
      elderly and younger adult patients with pneumonia. Age, nutritional status,
      smoking habit and diabetes mellitus were not associated with HBD2 concentration;
      however, COPD was associated with HBD2 concentration (p-value = 0.014).
      CONCLUSION: there is no mean concentration difference of HBD2 in the sputum of
      elderly and younger adult with pneumonia. There is association between COPD with
      HBD2 concentrations in the sputum of patients with pneumonia.

PMID- 22156352
TI  - Effect of dark chocolate on nitric oxide serum levels and blood pressure in
      prehypertension subjects.
AB  - AIM: to investigate the effect of consumption of dark chocolate 30 g/day for
      fifteen days on Nitric oxide (NO) serum levels and blood pressure in male and
      female employees with prehypertension. METHODS: the study was a parallel
      randomized clinical trial. A total of thirty-two subjects was divided into two
      groups using block randomization. Sixteen subjects received 30 g/day dark
      chocolate and dietary counseling (treatment group) and the other 16 subjects
      received white chocolate 25 g/day and dietary counseling (control group) for
      fifteen days. Data collected in this study consisted of age, physical activity,
      body massa index, intake of energy, intake of sodium, and intake of polyphenol,
      NO serum levels and blood pressure. The measurement of NO serum levels was done
      in pre- and after- treatment, while blood pressure was assessed in pre- , during-
      and after- treatment. Statistical analysis was performed using independent t-test
      for normal distribution data and Mann-Whitney test for not normal distribution
      data, with the level of significancy of 5%. RESULTS: after 15 days treatment, NO
      serum level between treatment and control groups were significantly different
      7.70 +/- 3.84 vs 1.92(-0.79 +/- 17.78) (p=0.001). Both groups had decreased
      systolic and diastolic blood pressure. Systolic blood pressure was different
      significantly between groups after treatment 120.64 +/- 8.47 vs 131.19 +/- 7.45
      (p=0.001), while diastolic blood pressure was not significant 74.14 +/- 6.30 vs
      77.44 +/- 10.29 (p=0.308). CONCLUSION: in prehypertension subjects, dark
      chocolate 30 g/day increased NOx serum levels and decreased systolic blood
      pressure after 15 days of treatment.

PMID- 22156353
TI  - Delayed gastric emptying in an indonesian population with reflux esophagitis.
AB  - AIM: to observe the delayed gastric emptying in patients with reflux esophagitis
      as well as to recognize the proportion of GERD patients who have delayed gastric
      emptying in Indonesian population by using standard scintigraphic method.
      METHODS: patients with heartburn and/or regurgitation in the last six-month
      period were included in the study. After endoscopic examination of upper
      gastrointestinal tract, scintigraphic examination was performed in appropriate to
      Consensus Recommendation for Gastric Emptying Scintigraphy with standard 99Tc
      labeled egg-white meal of 255 kcal. Delayed gastric emptying was defined when
      there was gastric retention >90% at 1 hour, >60% at 2 hours and >10% at 4 hours.
      RESULTS: twenty-three patients with reflux esophagitis were compared to 23
      subjects with Non-erosive reflux disease (NERD). Subjects with reflux esophagitis
      demonstrated slower gastric emptying compared to subjects with NERD at 1 hour
      (p<0.05), 2 hours (p<0.05) and 4 hours (p<0.05). Gastric retention >10% at 4
      hours was found in 6% patients with GERD (2 patients with reflux esophagitis and
      1 patient with NERD). CONCLUSION: gastric emptying in patients with reflux
      esophagitis is significantly slower than in patients with NERD.

PMID- 22156354
TI  - Combination of PPI with a prokinetic drug in gastroesophageal reflux disease.
AB  - AIM: to evaluate the efficacy of combination of PPI with prokinetic drug compared
      to PPI mono therapy in GERD patients with high frequency scale for the symptoms
      of GERD (FSSG) score. METHODS: sixty dyspeptic patients having heartburn and/or
      regurgitation were recruited during the period of July 2010-April 2011 in this
      double blind clinical trial. By randomization, they were divided into two groups;
      group A was given omeprazole 2 x 20 mg and domperidone 3 x 10 mg for 2 weeks,
      while another group was only given omeprazole 2 x 20 mg. The FSSG score was
      performed before treatment and after 2 weeks of treatment. RESULTS: there were 20
      (33%) males and 40 (67%) females. The mean total score of FSSG was 25.3 +/- 8.2
      at pretest, and 19.3 +/- 9.7 at posttest, with improvement of 6.1 +/- 4.9. The
      FSSG score in group A after treatment (19.3 +/- 11.3) was significantly lower
      than before treatment (26.7 +/- 8.9, p<0.001) as well as in group B (from 23.9 +/
      7.3 to 19,3 +/- 7.9, p<0.001). The mean improvement score in group A was 7.5 +/-
      5.9, while in the group B was of 4.6 +/- 3.3, and this difference was
      statistically significant (p=0.02) CONCLUSION: combination of omeprazole with
      domperidone in GERD patients with high FSSG score is more superior compared to
      omeprazole monotherapy.

PMID- 22156355
TI  - Predictors and scoring system for health-related quality of life in an Indonesian
      community-dwelling elderly population.
AB  - AIM: to determine factors that independently predict health-related quality of
      life of Indonesian community-dwelling elderly and to obtain scoring system to
      predict their quality of life. METHODS: this is a cross-sectional study covering
      a sample representative of the Indonesian community-dwelling elderly. The study
      was conducted among 487 elderly in 43 cities in Indonesia between November
      December 2010. A structured questionnaire was applied to obtain independent
      variable such as age, sex, number of diseases, present activities, functional
      status (ADL score), cognitive status (AMT score), nutritional status (NRI score),
      and depression status. Quality of life as dependent variable was assessed by
      Euroqol-5D (Eq-5D). We defined good quality of life as 3 or more dimensions of
      Eq5D having score of 1. Predictors of quality of life were identified using
      multiple logistic regression analysis. We constructed a scoring system based on
      coefficients in multivariable analysis. Calibration performance of the score was
      evaluated by Hosmer-Lemeshow tests while discrimination performance was evaluated
      with the c-statistic. RESULTS: most of the subjects were male (52.2%) and aged
      between 60-70 years old (75.8%). Prevalence of poor quality of life in this study
      was 14.9%. Bivariable analysis showed that all independent variables were
      significantly associated with quality of life. Multiple logistic regression
      analysis showed that factors predicting poor quality of life were female (OR 1.9;
      95% CI 1.0-3.6), poor nutritional status (OR 2.7; 95% CI (1.2-0.8), having >2
      chronic diseases (OR 3.6; 95% CI 1.9-6.8), low functional status (OR 4.2; 95% CI
      2.2-8.2), and depression (OR 6.3; 95% CI 3.3-12.1). Performance of the risk score
      revealed Hosmer Lemeshow test p=0.86 and c-statistic 0.87 (95% CI 0.83-0.92).
      CONCLUSION: the following factors were identified as predictive factors of HRQoL
      in Indonesian community-dwelling elderly: sex, nutritional status, number of
      chronic diseases, functional status, and depression status. The risk score
      developed based on those predictors showed good performance to accurately predict
      poor quality of life.

PMID- 22156356
TI  - Gastric ulcers induced by systemic hypoxia.
AB  - AIM: to assess the effect of systemic hypoxia on gastric mucosa and the
      activation of stress-responsive transcription factors induced by hypoxia.
      METHODS: in this experimental study, rats were allocated to control and
      experimental groups. The experimental group was divided into subgroups and
      subjected to hypoxia conditions for 1, 7, 14 or 21 days. Afterwards,
      histopathological evaluation and study of the protein expression of the gastric
      mucosa were performed. RESULTS: the results showed that longer exposure to
      hypoxic conditions leads to more severe gastric ulceration. Twenty-four hours
      after induction, 60% of rats had developed gastric ulcers. Seven days after
      induction, 80% of rats developed gastric ulcers. In the 14-day and 21-day hypoxia
      conditions, epithelialization (a sign of gastric ulcer healing) was observed.
      Evaluation of the average ulcer depth on the day of treatment showed that the
      greatest depth was on day 7, and the shallowest was on day 21 of treatment.
      Western blot analyses demonstrated that systemic hypoxia resulted in the
      expression of heat shock factor (HSF) and heat shock protein 70 (HSP-70), which
      were highest on day 7 and then regressed gradually. In control, HSF-1 and HSP-70
      were not detected by Western blot analysis in the control group (normoxia).
      CONCLUSION: in this study, systemic hypoxia caused gastric ulcers, and during the
      time of exposure to hypoxia, an adaptation process in the form of gastric
      epithelialization occurred in the rats. This development of gastric lesions was
      in line with the expression pattern of HSF-1 HIF-1 and HSP-70.

PMID- 22156357
TI  - Filariasis presenting as multiple subcutaneous nodules: a rare case report.
AB  - Filariasis presenting as multiple subcutaneous nodules is very rare and only a
      very few cases are reported in the literature. Microfilaria bancrofti is known to
      occur in different sites like breast, thyroid, lymph nodes, liver, lungs and body
      fluids, however, in contrast to the other filarial species, its occurrence in
      soft tissues is rarely reported. Conventional method of diagnosis of filariasis
      is by demonstration of microfilaria in peripheral blood smear which may be
      diurnal or nocturnal. The various species are differentiated by the morphological
      features like presence or absence of sheath, granules and nuclear arrangement in
      the tail end. We hereby report an unusual case of Wuchereria bancrofti
      infestation diagnosed on biopsy of subcutaneous nodule in a patient whose initial
      clinical presentation was of urticarial rashes over the upper extremities.  In
      differential diagnosis of various subcutaneous nodular masses the possibility of
      filarial granuloma must be kept and a careful search should be done for adult
      worm or microfilaria in the serial tissue sections.

PMID- 22156358
TI  - Allogenic hematopoietic stem cell as curative treatment in myelofibrosis.
AB  - Myelofibrosis (MF) is one of the Philadelphia chromosome-negative clonal
      myeloproliferative disorders or chronic myeloid disorders, and it is caused by
      much deposit of collagen substances in bone marrow, definitely is classified as
      hematopoietic stem cells clonal abnormality, and related to chronic
      myeloproliferative disorders characterized by striking figure of extra-medullary
      hematopoiesis.  Symptoms and signs of MF are included the variable degree of
      cachexia and marked extra-medullary hematopoiesis. The results of laboratory
      studies at presentation include anemia, leukocytosis or leucopenia, a left-ward
      shift in the granulocyte count, increased or decreased platelet count.  Many
      conventional treatment modalities have been used in the MF treatment as
      supportive treatments. There is only one curative treatment in MF patients using
      allogenic hematopoietic stem cell transplantation (HSTC). The umbilical cord
      blood (UCB) as the source of stem cell has increased recently and gives promising
      results on MF.

PMID- 22156359
TI  - Obstructive jaundice due to ductus hepaticus communis cyst in patient with liver
      cirrhosis.

PMID- 22156360
TI  - The role of prophylactic antibiotics in preventing perioperative infection.
AB  - With the increasing number of surgery or operation, perioperative infection has
      become one of problems that have been found more often. Surgical site infection
      is the most common perioperative infection causing increased hospitalization
      stay, high cost, morbidity and mortality rate. Infection occurs within 30 days
      after the operation on surgical site or within one year if implant is in place.
      Such infection may be prevented through several ways including some aspects of
      health-care provider, operating-room environment, and adequate preoperative
      preparation of the patients. Antibiotic prophylaxis is one of important
      modalities in preventing surgical site infection. Antibiotic prophylaxis
      administration significantly reduces the incidence of surgical site infection up
      to four-fold of decrease. Short-term antibiotic is given prior to incision in
      order to reduce the contamination of bacterial inoculums during surgery. The
      decision to administer antibiotic prophylaxis should be made by considering their
      risk and benefits. One of them includes utilization of the NNIS (National
      Nosocomial Infections Surveillance) score system, which considers three factors,
      such as wound class, ASA physical status scale, and duration of operation
      according to the NNIS Survey. The selection on timing and appropriately
      administered antibiotic prophylaxis is critical to maximize the benefits.

PMID- 22156361
TI  - National consensus on the management of constipation in indonesia 2010.
AB  - Constipation is a common complaint in our daily practice, which may occur in
      young adult or elderly patients. Recently, the incidence has been increasing;
      however, most patients try to have self-medication using over-the-counter (OTC)
      drugs, which is usually inappropriate. Moreover, there has been unequal
      distribution of knowledge and vigilance of medical practitioners, both general
      physician and specialist doctors on the constipation issue. Therefore, patients
      usually present with greater complications.  The Organizing Committee of
      Indonesian Society of Gastroenterology or Pengurus Besar Perkumpulan
      Gastroenterologi Indonesia (PB PGI) considers that it is important to compose a
      National Consensus on the Management of Constipation in Indonesia. The Consensus
      is expected to be a guideline for doctors to deal with patients who have
      constipation in their daily practice, so that optimal results could be achieved. 
      Nowadays, there are new data on definition, pathophysiology, diagnosis and
      management of constipation; thus, the Organizing Committee of ISG feels that it
      is necessary to revise the established consensus. We expect that the consensus
      may bring advantages for medical practitioners in Indonesia and in general, it
      may cause community health improvement.

PMID- 22156363
TI  - Activation of p38 mitogen-activated protein kinase is inhibited by hyaluronan via
      intercellular adhesion molecule-1 in articular chondrocytes stimulated with type
      II collagen peptide.
AB  - This study examined the activation of p38 mitogen-activated protein kinase with
      matrix metalloproteinase-13 (MMP-13) production by a synthetic peptide derived
      from type II collagen (CB12-II) and its inhibition by high molecular weight
      hyaluronan (HA) in chondrocytes. When cartilage explants or isolated chondrocytes
      in monolayer were incubated with CB12-II, the peptide (50 uM, 72 h) activated p38
      in association with enhanced MMP-13 production. Inhibition studies with SB203580
      (0.1 - 1 uM) indicated the requirement of p38 for CB12-II-induced MMP-13
      production. Pretreatment with 2700 kDa HA (1 mg/ml, 1 h) resulted in significant
      suppression of CB12-II-stimulated MMP-13 production in cartilage as well as in
      chondrocyte monolayer cultures. HA (1 mg/ml) suppressed p38 activation by CB12
      II, leading to a decrease in MMP-13 production. The antibody (20 ug/ml) to
      intercellular adhesion molecule-1 (ICAM-1), which has been recognized as a
      receptor of HA on chondrocytes, reversed the HA effect on CB12-II action. Thus,
      the present study clearly demonstrated that high molecular weight HA suppressed
      CB12-II-activated p38 via ICAM-1 in articular chondrocytes. HA could down
      regulate the catabolic action of type II collagen fragments in osteoarthritic
      joints through the mechanism demonstrated in this study.

PMID- 22156364
TI  - Inhibition of membrane Na+ channels by A type botulinum toxin at femtomolar
      concentrations in central and peripheral neurons.
AB  - Recent studies have demonstrated that the botulinum neurotoxins inhibit the
      release of acetylcholine, glutamate, GABA, and glycine in central nerve system
      (CNS) neurons. The Na(+) current (I(Na)) is of major interest because it acts as
      the trigger for many cellular functions such as transmission, secretion,
      contraction, and sensation. Thus, these observations raise the possibility that A
      type neurotoxin might also alter the I(Na) of neuronal excitable membrane. To
      test our idea, we examined the effects of A type neurotoxins on I(Na) of central
      and peripheral neurons. The neurotoxins in femtomolar to picomolar concentrations
      produced substantial decreases of the neuronal I(Na), but interestingly the
      current inhibition was saturated at about maximum 50% level of control I(Na). The
      inhibitory pattern in the concentration-response curve for the neurotoxins
      differed from tetrodotoxin (TTX), local anesthetic, and antiepileptic drugs that
      completely inhibited I(Na) in a concentration-dependent manner. We concluded that
      A type neurotoxins inhibited membrane Na(+)-channel activity in CNS neurons and
      that I(Na) of both TTX-sensitive and -insensitive peripheral dorsal ganglion
      cells were also inhibited similarly to a maximum 40% of the control by the
      neurotoxins. The results suggest evidently that A2NTX could be also used as a
      powerful drug in treating epilepsy and several types of pain.

PMID- 22156365
TI  - METU-SNP: an integrated software system for SNP-complex disease association
      analysis.
AB  - Recently, there has been increasing research to discover genomic biomarkers,
      haplotypes, and potentially other variables that together contribute to the
      development of diseases. Single Nucleotide Polymorphisms (SNPs) are the most
      common form of genomic variations and they can represent an individual&rsquo;s
      genetic variability in greatest detail. Genome-wide association studies (GWAS) of
      SNPs, high-dimensional case-control studies, are among the most promising
      approaches for identifying disease causing variants. METU-SNP software is a Java
      based integrated desktop application specifically designed for the prioritization
      of SNP biomarkers and the discovery of genes and pathways related to diseases via
      analysis of the GWAS case-control data. Outputs of METU-SNP can easily be
      utilized for the downstream biomarkers research to allow the prediction and the
      diagnosis of diseases and other personalized medical approaches. Here, we
      introduce and describe the system functionality and architecture of the METU-SNP.
      We believe that the METU-SNP will help researchers with the reliable
      identification of SNPs that are involved in the etiology of complex diseases,
      ultimately supporting the development of personalized medicine approaches and
      targeted drug discoveries.

PMID- 22156366
TI  - Magnetic resonance venous velocity mapping during intermittent pneumatic
      compression of the calf and foot.
AB  - OBJECTIVE: Assessment and optimization of intermittent pneumatic compression
      (IPC) devices for prophylaxis of deep vein thrombosis has previously used duplex
      ultrasound. The aim was to investigate novel magnetic resonance (MR) venous
      velocity mapping (VM) for IPC research and development. METHODS: Twelve normal
      subjects were scanned in the supine position using realtime MR VM with sequential
      foot and calf IPC (120 mmHg) at 1.5 T. Measurements were taken in the popliteal
      vein at baseline using both cuffs and each cuff individually recording 60 seconds
      continuously. Temporal resolution was 310 ms per independent image, at 1 * 1 mm
      spatial resolution. RESULTS: Peak velocity (V(p)) measurements: baseline, V(p) =
      2.1 cm/second (range = 1.1-3.5); using both compression cuffs, V(p) = 41.5
      cm/second (18.0-58.1); calf cuff alone, V(p) = 40.6 cm/second (18.1-62.2); foot
      cuff alone, V(p) = 7.9 cm/second (4.2-15.3). Flow volume measurements per
      compression cycle (F): baseline, F = 2.3 cm3 (0.5-11.4); both compression cuffs,
      F = 7.1 cm3 (2.5-24.6); calf cuff only, F = 7.1 cm3 (2.4-24.5); foot cuff only, F
      = 2.6 cm3 (0.9-10.7). The foot cuff contribution was insignificant when combined
      with the calf cuff (P < 0.01). The MR venous VM results were similar to those
      reported elsewhere using ultrasound. CONCLUSION: This novel technique for MR
      venous VM can measure the realtime variations in venous blood flow during IPC.

PMID- 22156367
TI  - Optimized application of penalized regression methods to diverse genomic data.
AB  - MOTIVATION: Penalized regression methods have been adopted widely for high
      dimensional feature selection and prediction in many bioinformatic and
      biostatistical contexts. While their theoretical properties are well-understood,
      specific methodology for their optimal application to genomic data has not been
      determined. RESULTS: Through simulation of contrasting scenarios of correlated
      high-dimensional survival data, we compared the LASSO, Ridge and Elastic Net
      penalties for prediction and variable selection. We found that a 2D tuning of the
      Elastic Net penalties was necessary to avoid mimicking the performance of LASSO
      or Ridge regression. Furthermore, we found that in a simulated scenario favoring
      the LASSO penalty, a univariate pre-filter made the Elastic Net behave more like
      Ridge regression, which was detrimental to prediction performance. We demonstrate
      the real-life application of these methods to predicting the survival of cancer
      patients from microarray data, and to classification of obese and lean
      individuals from metagenomic data. Based on these results, we provide an
      optimized set of guidelines for the application of penalized regression for
      reproducible class comparison and prediction with genomic data. AVAILABILITY AND
      IMPLEMENTATION: A parallelized implementation of the methods presented for
      regression and for simulation of synthetic data is provided as the pensim R
      package, available at http://cran.r-project.org/web/packages/pensim/index.html.
      CONTACT: chuttenh@hsph.harvard.edu; juris@ai.utoronto.ca SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 22156368
TI  - Prior use of antiplatelet therapy can be associated with a higher chance for
      early recanalization of the occluded middle cerebral artery in acute stroke
      patients treated with intravenous thrombolysis.
AB  - BACKGROUND: The early recanalization (ER) of an occluded cerebral artery is
      important for clinical improvement in acute ischemic stroke. The aim of the study
      was to assess the possible association between the prior use of antiplatelets
      (AP) and ER of occluded middle cerebral artery (MCA) after intravenous
      thrombolysis (IVT). METHODS: In 146 consecutive acute ischemic stroke patients
      presenting with occluded MCA and treated with IVT, the ER and incidence of
      symptomatic intracerebral hemorrhage (SICH) were compared according to the
      presence or absence of prior AP use. ER was assessed by transcranial Doppler or
      digital subtraction angiography within 2 h after the end of IVT. RESULTS: Fifty
      six patients (28 males, mean age: 69.8 +/- 9.8 years) used AP and 90 patients
      were AP naive (51 males, mean age: 65.8 +/- 12.5 years). Prior AP use was
      associated with a higher rate of early MCA recanalization (53.6 vs. 29.5% in AP
      naive, p = 0.007) and was shown as a predictor of ER (OR: 2.30, 95% CI: 1.14
      4.65; p = 0.020) in unadjusted analysis. No difference was found in the
      occurrence of SICH. CONCLUSION: Prior use of AP was associated with a higher rate
      of ER of occluded MCA, but with no increase of SICH after IVT.

PMID- 22156369
TI  - New function for the RNA helicase p68/DDX5 as a modifier of MBNL1 activity on
      expanded CUG repeats.
AB  - Myotonic Dystrophy type I (DM1) is caused by an abnormal expansion of CTG
      triplets in the 3' UTR of the dystrophia myotonica protein kinase (DMPK) gene,
      leading to the aggregation of the mutant transcript in nuclear RNA foci. The
      expanded mutant transcript promotes the sequestration of the MBNL1 splicing
      factor, resulting in the misregulation of a subset of alternative splicing
      events. In this study, we identify the DEAD-box RNA helicase p68 (DDX5) in
      complexes assembled onto in vitro-transcribed CUG repeats. We showed that p68
      colocalized with RNA foci in cells expressing the 3'UTR of the DMPK gene
      containing expanded CTG repeats. We found that p68 increased MBNL1 binding onto
      pathological repeats and the stem-loop structure regulatory element within the
      cardiac Troponin T (TNNT2) pre-mRNA, splicing of which is misregulated in DM1.
      Mutations in the helicase core of p68 prevented both the stimulatory effect of
      the protein on MBNL1 binding and the colocalization of p68 with CUG repeats,
      suggesting that remodeling of RNA secondary structure by p68 facilitates MBNL1
      binding. We also found that the competence of p68 for regulating TNNT2 exon 5
      inclusion depended on the integrity of MBNL1 binding sites. We propose that p68
      acts as a modifier of MBNL1 activity on splicing targets and pathogenic RNA.

PMID- 22156370
TI  - Structural activation of the transcriptional repressor EthR from Mycobacterium
      tuberculosis by single amino acid change mimicking natural and synthetic ligands.
AB  - Ethionamide is an antituberculous drug for the treatment of multidrug-resistant
      Mycobacterium tuberculosis. This antibiotic requires activation by the
      monooxygenase EthA to exert its activity. Production of EthA is controlled by the
      transcriptional repressor EthR, a member of the TetR family. The sensitivity of
      M. tuberculosis to ethionamide can be artificially enhanced using synthetic
      ligands of EthR that allosterically inactivate its DNA-binding activity.
      Comparison of several structures of EthR co-crystallized with various ligands
      suggested that the structural reorganization of EthR resulting in its
      inactivation is controlled by a limited portion of the ligand-binding-pocket. In
      silico simulation predicted that mutation G106W may mimic ligands. X-ray
      crystallography of variant G106W indeed revealed a protein structurally similar
      to ligand-bound EthR. Surface plasmon resonance experiments established that this
      variant is unable to bind DNA, while thermal shift studies demonstrated that
      mutation G106W stabilizes EthR as strongly as ligands. Proton NMR of the methyl
      regions showed a lesser contribution of exchange broadening upon ligand binding,
      and the same quenched dynamics was observed in apo-variant G106W. Altogether, we
      here show that the area surrounding Gly106 constitutes the molecular switch
      involved in the conformational reorganization of EthR. These results also shed
      light on the mechanistic of ligand-induced allosterism controlling the DNA
      binding properties of TetR family repressors.

PMID- 22156371
TI  - Human PSF concentrates DNA and stimulates duplex capture in DMC1-mediated
      homologous pairing.
AB  - PSF is considered to have multiple functions in RNA processing, transcription and
      DNA repair by mitotic recombination. In the present study, we found that PSF is
      produced in spermatogonia, spermatocytes and spermatids, suggesting that PSF may
      also function in meiotic recombination. We tested the effect of PSF on homologous
      pairing by the meiosis-specific recombinase DMC1, and found that human PSF
      robustly stimulated it. PSF synergistically enhanced the formation of a synaptic
      complex containing DMC1, ssDNA and dsDNA during homologous pairing. The PSF
      mediated DMC1 stimulation may be promoted by its DNA aggregation activity, which
      increases the local concentrations of ssDNA and dsDNA for homologous pairing by
      DMC1. These results suggested that PSF may function as an activator for the
      meiosis-specific recombinase DMC1 in higher eukaryotes.

PMID- 22156372
TI  - Quantitative prediction of 3D solution shape and flexibility of nucleic acid
      nanostructures.
AB  - DNA nanotechnology enables the programmed synthesis of intricate nanometer-scale
      structures for diverse applications in materials and biological science. Precise
      control over the 3D solution shape and mechanical flexibility of target designs
      is important to achieve desired functionality. Because experimental validation of
      designed nanostructures is time-consuming and cost-intensive, predictive physical
      models of nanostructure shape and flexibility have the capacity to enhance
      dramatically the design process. Here, we significantly extend and experimentally
      validate a computational modeling framework for DNA origami previously presented
      as CanDo [Castro,C.E., Kilchherr,F., Kim,D.-N., Shiao,E.L., Wauer,T.,
      Wortmann,P., Bathe,M., Dietz,H. (2011) A primer to scaffolded DNA origami. Nat.
      Meth., 8, 221-229.]. 3D solution shape and flexibility are predicted from
      basepair connectivity maps now accounting for nicks in the DNA double helix,
      entropic elasticity of single-stranded DNA, and distant crossovers required to
      model wireframe structures, in addition to previous modeling (Castro,C.E., et
      al.) that accounted only for the canonical twist, bend and stretch stiffness of
      double-helical DNA domains. Systematic experimental validation of nanostructure
      flexibility mediated by internal crossover density probed using a 32-helix DNA
      bundle demonstrates for the first time that our model not only predicts the 3D
      solution shape of complex DNA nanostructures but also their mechanical
      flexibility. Thus, our model represents an important advance in the quantitative
      understanding of DNA-based nanostructure shape and flexibility, and we anticipate
      that this model will increase significantly the number and variety of synthetic
      nanostructures designed using nucleic acids.

PMID- 22156373
TI  - Structural and functional analysis of the archaeal endonuclease Nob1.
AB  - Eukaryotic ribosome biogenesis requires the concerted action of numerous ribosome
      assembly factors, for most of which structural and functional information is
      currently lacking. Nob1, which can be identified in eukaryotes and archaea, is
      required for the final maturation of the small subunit ribosomal RNA in yeast by
      catalyzing cleavage at site D after export of the preribosomal subunit into the
      cytoplasm. Here, we show that this also holds true for Nob1 from the archaeon
      Pyrococcus horikoshii, which efficiently cleaves RNA-substrates containing the D
      site of the preribosomal RNA in a manganese-dependent manner. The structure of
      PhNob1 solved by nuclear magnetic resonance spectroscopy revealed a PIN domain
      common with many nucleases and a zinc ribbon domain, which are structurally
      connected by a flexible linker. We show that amino acid residues required for
      substrate binding reside in the PIN domain whereas the zinc ribbon domain alone
      is sufficient to bind helix 40 of the small subunit rRNA. This suggests that the
      zinc ribbon domain acts as an anchor point for the protein on the nascent subunit
      positioning it in the proximity of the cleavage site.

PMID- 22156374
TI  - Bio-CAP: a versatile and highly sensitive technique to purify and characterise
      regions of non-methylated DNA.
AB  - Across vertebrate genomes methylation of cytosine residues within the context of
      CpG dinucleotides is a pervasive epigenetic mark that can impact gene expression
      and has been implicated in various developmental and disease-associated
      processes. Several biochemical approaches exist to profile DNA methylation, but
      recently an alternative approach based on profiling non-methylated CpGs was
      developed. This technique, called CxxC affinity purification (CAP), uses a ZF
      CxxC (CxxC) domain to specifically capture DNA containing clusters of non
      methylated CpGs. Here we describe a new CAP approach, called biotinylated CAP
      (Bio-CAP), which eliminates the requirement for specialized equipment while
      dramatically improving and simplifying the CxxC-based DNA affinity purification.
      Importantly, this approach isolates non-methylated DNA in a manner that is
      directly proportional to the density of non-methylated CpGs, and discriminates
      non-methylated CpGs from both methylated and hydroxymethylated CpGs. Unlike
      conventional CAP, Bio-CAP can be applied to nanogram quantities of genomic DNA
      and in a magnetic format is amenable to efficient parallel processing of samples.
      Furthermore, Bio-CAP can be applied to genome-wide profiling of non-methylated
      DNA with relatively small amounts of input material. Therefore, Bio-CAP is a
      simple and streamlined approach for characterizing regions of the non-methylated
      DNA, whether at specific target regions or genome wide.

PMID- 22156375
TI  - HDAC1 regulates pluripotency and lineage specific transcriptional networks in
      embryonic and trophoblast stem cells.
AB  - Epigenetic regulation of gene expression is important in maintaining self-renewal
      of embryonic stem (ES) and trophoblast stem (TS) cells. Histone deacetylases
      (HDACs) negatively control histone acetylation by removing covalent acetylation
      marks from histone tails. Because histone acetylation is a known mark for active
      transcription, HDACs presumably associate with inactive genes. Here, we used
      genome-wide chromatin immunoprecipitation to investigate targets of HDAC1 in ES
      and TS cells. Through evaluation of genes associated with acetylated histone H3
      marks, and global expression analysis of Hdac1 knockout ES and trichostatin A
      treated ES and TS cells, we found that HDAC1 occupies mainly active genes,
      including important regulators of ES and TS cells self-renewal. We also observed
      occupancy of methyl-CpG binding domain protein 3 (MBD3), a subunit of the
      nucleosome remodeling and histone deacetylation (NuRD) complex, at a subset of
      HDAC1-occupied sequences in ES cells, including the pluripotency regulators Oct4,
      Nanog and Kfl4. By mapping HDAC1 targets on a global scale, our results describe
      further insight into epigenetic mechanisms of ES and TS cells self-renewal.

PMID- 22156377
TI  - Tetrahydrocurcumin extends life span and inhibits the oxidative stress response
      by regulating the FOXO forkhead transcription factor.
AB  - The O-type forkhead domain transcription factor (FOXO) is involved in many
      biological processes such as aging, the oxidative stress response, and growth
      regulation. FOXO activity is tightly controlled within cells. In particular,
      growth factor signaling pathways and the oxidative stress response can both
      stimulate nuclear translocation of this transcription factor. Here, we show that
      tetrahydrocurcumin (THC), a curcumin metabolite, regulates the oxidative stress
      response and aging via FOXO. In NIH3T3 cells, THC induced nuclear accumulation of
      FOXO4, a member of the FOXO family of transcription factors, by inhibiting
      phosphorylation of protein kinase B (PKB)/Akt. In Drosophila melanogaster, THC
      attenuated the oxidative stress response, an effect that was blocked in a foxo
      mutant background. THC also extended the life span of Drosophila under normal
      conditions, and loss of either foxo or Sir2 activity eliminated this effect.
      Based on these results, THC may regulate the aging process via an evolutionarily
      conserved signaling pathway that includes both foxo and Sir2.

PMID- 22156378
TI  - Preovulatory follicular and subsequent luteal size influence pregnancy success in
      water buffaloes.
AB  - The diameter of the preovulatory follicle (POF) and its effects on subsequent
      corpus luteum (CL) size and conception were studied in 38 lactating indigenous
      cycling buffaloes in the Mymensingh district of Bangladesh. Body condition score
      (BCS) at estrus was estimated for the buffaloes. The buffaloes were synchronized
      with two injections of a synthetic analogue of PGF2alpha administered 11 days
      apart. Transrectal ultrasonography was carried out at estrus and on days 5, 9, 12
      and 16 post ovulation to determine the POF and successive CL size. Pregnancy was
      confirmed by ultrasound examination on day 40-45 post ovulation. Twenty one
      (55.3%) buffaloes were diagnosed as pregnant. The conception rates of thin (BCS
      <=2.0), good (BCS 2.5-3.5) and fat (BCS glt;3.5) buffaloes were 7.7, 88.2 and
      62.5% (chi2 = 19.54; P<0.05), respectively. The mean diameter of the POF at
      estrus was larger (P<0.01) in buffaloes that ultimately were diagnosed as
      pregnant compared with their nonpregnant counterparts (13.7 +/- 0.3 vs. 11.2 +/-
      0.5 mm, respectively). The conception rates of buffaloes having small (9 to <= 12
      mm), medium (>12 to <=14 mm) and large (>14 to 16 mm) POFs at estrus were 9.1,
      70.0 and 85.7% (chi2 = 13.87, P<0.01), respectively. On day 5 post ovulation, CL
      size was positively correlated (CL: r=.74, P<0.01) with POF diameter.
      Retrospective analysis revealed that on day 5 post ovulation, the pregnant
      buffaloes had higher (P<0.01) post ovulation CL sizes than their nonpregnant
      counterparts (15.6 vs. 11.8 mm). Similarly, on day 9 post ovulation, the
      difference in CL size (14.3 vs. 13.6 mm) between pregnant and nonpregnant
      buffaloes was significant (P<0.05). In conclusion, the diameter of the POF in
      buffaloes has a positive impact on the size of the post ovulation CL and
      conception.

PMID- 22156376
TI  - Functional binding of hexanucleotides to 3C protease of hepatitis A virus.
AB  - Oligonucleotides as short as 6 nt in length have been shown to bind specifically
      and tightly to proteins and affect their biological function. Yet, sparse
      structural data are available for corresponding complexes. Employing a recently
      developed hexanucleotide array, we identified hexadeoxyribonucleotides that bind
      specifically to the 3C protease of hepatitis A virus (HAV 3C(pro)). Inhibition
      assays in vitro identified the hexanucleotide 5'-GGGGGT-3' (G(5)T) as a 3C(pro)
      protease inhibitor. Using (1)H NMR spectroscopy, G(5)T was found to form a G
      quadruplex, which might be considered as a minimal aptamer. With the help of
      (1)H, (15)N-HSQC experiments the binding site for G(5)T was located to the C
      terminal beta-barrel of HAV 3C(pro). Importantly, the highly conserved KFRDI
      motif, which has previously been identified as putative viral RNA binding site,
      is not part of the G(5)T-binding site, nor does G(5)T interfere with the binding
      of viral RNA. Our findings demonstrate that sequence-specific nucleic acid
      protein interactions occur with oligonucleotides as small as hexanucleotides and
      suggest that these compounds may be of pharmaceutical relevance.

PMID- 22156380
TI  - Beneficial effect of hyperbaric oxygen therapy on the follicular survival in the
      mouse ovary after transplantation.
AB  - A large proportion of follicles are lost during the initial ischemia that occurs
      after transplantation of ovarian tissues. Thus, the effect of hyperbaric oxygen
      therapy (HBO) on the follicular loss of ovarian tissues after transplantation was
      examined in mice. Ovarian slices from ICR mice were transplanted under the kidney
      capsule in ovariectomized ICR. Hyperbaric oxygen with 100% oxygen was initiated
      for 30 min at 2.5 atmospheres absolute immediately after transplantation, and
      this treatment was repeated at 48-h intervals for 2 weeks. The number of
      follicles was dramatically reduced at 2 weeks post transplantation. However, HBO
      was significantly effective in enhancing the survival of transplanted ovarian
      follicles. The survival rates of primordial and primary follicles in ovarian
      tissues of mice with HBO were significantly higher than those without HBO. These
      results indicate HBO can be effectively used for the enhancement of survival of
      transplanted ovarian tissues.

PMID- 22156379
TI  - Effects of cortisol on pregnancy rate and corpus luteum function in heifers: an
      in vivo study.
AB  - To determine whether glucocorticoids affect the function of the bovine corpus
      luteum (CL) during the estrous cycle and early pregnancy, we examined the effects
      of exogenous cortisol or reduced endogenous cortisol on the secretion of
      progesterone (P4) and on pregnancy rate. In preliminary experiments, doses of
      cortisol and metyrapone (an inhibitor of cortisol synthesis) were established
      (n=33). Cortisol in effective doses of 10 mg blocked tumor necrosis factor
      induced prostaglandin F(2alpha) secretion as measured by its metabolite (PGFM)
      concentrations in the blood. Metyrapone in effective doses of 500 mg increased
      the P4 concentration. Thus, both reagents were then intravaginally applied in the
      chosen doses daily from Day 15 to 18 after estrus (Day 0) in noninseminated
      heifers (n=18) or after artificial insemination (n=36). Pregnancy was confirmed
      by transrectal ultrasonography between Days 28-30 after insemination. Plasma
      concentrations of P4 were lower in cortisol-treated heifers than in control
      heifers on Days 17 and 18 of the estrous cycle (P<0.05). However, the interestrus
      intervals were not different between control and cortisol-treated animals
      (P>0.05). Moreover, metyrapone increased P4 and prolonged the CL lifespan in
      comparison to control animals (P<0.05). Interestingly, in inseminated heifers,
      cortisol increased the pregnancy rate (75%) compared with control animals (58%),
      whereas metyrapone reduced the pregnancy rate to 16.7% (P<0.05). The overall
      results suggest that cortisol, depending on the physiological status of heifers
      (pregnant vs. nonpregnant), modulates CL function by influencing P4 secretion.
      Cortisol may have a positive influence on CL function during early pregnancy,
      leading to support of embryo implantation and resulting in higher rates of
      pregnancy in heifers.

PMID- 22156382
TI  - Reliability of urodynamic interpretation in women presenting with urinary
      incontinence at a tertiary hospital.
AB  - BACKGROUND: Urodynamic testing is often regarded as essential to the proper
      diagnosis of bladder storage and emptying disorders but urodynamic testing is an
      invasive and expensive procedure. Pakistan is a developing country with limited
      provision of urogynecological services, and therefore few urodynamic studies.
      STUDY DESIGN: This cross-sectional study was conducted from January 2009 to
      January 2010 at the Aga Khan University Hospital to assess the frequency of
      agreement between clinical findings and urodynamic studies in accurately
      diagnosing urinary incontinence. METHODS: We included 157 women and their
      symptoms of urge urinary incontinence (UUI), stress urinary incontinence (SUI) or
      mixed urinary incontinence were matched with urodynamic study findings. RESULTS:
      Out of 157 women 47 (29.9%) presented with SUI and 33 (21%) with UUI but
      urodynamic stress incontinence (USI) was found in 59 (37.6%) and detrusor
      overactivity in 38 (24.2%). This shows a reliability level of K = 0.41 for SUI
      and K = 0.7 for UUI. There was a weak agreement (K = 0.33) between clinical
      findings of urinary incontinence and urodynamic studies; in 78 cases (49.7%) the
      urodynamic findings matched the clinical findings. CONCLUSIONS: The poor level of
      agreement between clinical findings and urodynamic study interpretations re
      emphasizes the fact that the bladder is not a reliable source of identifying
      urinary symptoms in women.

PMID- 22156381
TI  - The protective effect of zoledronic acid on bone loss in postmenopausal women
      with early breast cancer treated with sequential tamoxifen and letrozole: a
      prospective, randomized, phase II trial.
AB  - OBJECTIVE: This study reports the efficacy and safety of zoledronic acid (ZOL) in
      preventing bone loss in postmenopausal patients receiving an aromatase inhibitor
      (AI) following tamoxifen. METHODS: Postmenopausal patients with stage I-III
      hormone receptor-positive breast cancer who received tamoxifen for 2.5-3 years
      were randomized to receive letrozole (2.5 mg/day) with (n = 47) or without (n =
      43) ZOL (4 mg i.v. every 6 months) for 2 years. The primary endpoint was percent
      change from baseline in lumbar spine (LS) bone mineral density (BMD) up to 60
      months. RESULTS: Ninety patients (86 evaluable) with a median age of 59 years
      (42.9-83.6), 50/86 of whom had previously been treated with chemotherapy, were
      followed for a median time of 41.4 months. While the control group showed a
      significant decrease in LS T-score (p = 0.0005), the ZOL group presented an
      increase over time (p = 0.0143). Change over time in LS T-score was significantly
      different between groups, favoring ZOL (p < 0.0001 at 24 and 48 months). No
      fractures, renal dysfunction or osteonecrosis of the jaw were reported. The
      toxicity profile was similar to those previously reported for each drug.
      CONCLUSION: The addition of ZOL to letrozole was safe and efficacious in
      maintaining LS BMD in postmenopausal patients with hormone receptor-positive
      breast cancer and who were receiving letrozole following 2.5-3 years of
      tamoxifen.

PMID- 22156383
TI  - Isolation and characterization of novel mutant loci suppressing the ABA
      hypersensitivity of the Arabidopsis coronatine insensitive 1-16 (coi1-16) mutant
      during germination and seedling growth.
AB  - The phytohormone ABA regulates seed germination and stress responses. The
      identification of clade A protein phosphatase type 2C (PP2C)-interacting proteins
      PYRABACTIN RESISTANCE 1 (PYR1)/RCAR (REGULATORY COMPONENT OF ABA RECEPTOR) and
      PYR1-LIKEs (PYLs) as ABA receptors has been a major advance in understanding this
      process. Here, our aim was to identify additional ABA response loci by suppressor
      screening of the jasmonate (JA)-insensitive coronatine insensitive 1-16 (coi1-16)
      mutant using its ABA-hypersensitive phenotype. The identification and genetic
      characterization of Coi1-16 Resistant to ABA (CRA) loci revealed several unknown
      and three previously known abi mutants (abi1, abi3 and abi4), thus providing
      proof-of-concept evidence for this study. The synergistic effect of ABA and JA on
      seed germination and cotyledon expansion was analyzed in depth and the roles of
      cra5 coi1-16, cra6 coi1-16, cra7 coi1-16 and cra8 coi1-16 in ABA signaling during
      seed germination and stress responses were functionally characterized. The cra5
      coi1-16 mutant showed resistance to ABA, paclobutrazol, and abiotic stresses
      during germination and early developmental stages. Furthermore, the cra5 coi1-16
      mutation was mapped to the short arm of chromosome V and mutants exhibited
      differential expression of ABA-responsive genes, suggesting that CRA5 may
      function as a positive regulator of ABA signaling. Interestingly, cra6 coi1-16,
      cra7 coi1-16 and cra8 coi1-16 mutants display similar ABA- and abiotic stress
      insensitive phenotypes during seed germination and seedling establishment. Taken
      together, our results demonstrate a key role for CRA genes in regulating the
      onset of seed germination by ABA, and highlight how cra mutants can be used as
      powerful tools to analyze novel molecular components of ABA signaling in seeds.

PMID- 22156384
TI  - Ecotypic variability in the metabolic response of seeds to diurnal hydration
      dehydration cycles and its relationship to seed vigor.
AB  - Seeds in the seed bank experience diurnal cycles of imbibition followed by
      complete dehydration. These conditions pose a challenge to the regulation of
      germination. The effect of recurring hydration-dehydration (Hy-Dh) cycles were
      tested on seeds from four Arabidopsis thaliana accessions [Col-0, Cvi, C24 and
      Ler]. Diurnal Hy-Dh cycles had a detrimental effect on the germination rate and
      on the final percentage of germination in Col-0, Cvi and C24 ecotypes, but not in
      the Ler ecotype, which showed improved vigor following the treatments. Membrane
      permeability measured by ion conductivity was generally increased following each
      Hy-Dh cycle and was correlated with changes in the redox status represented by
      the GSSG/GSH (oxidized/reduced glutathione) ratio. Among the ecotypes, Col-0
      seeds displayed the highest membrane permeability, whilst Ler was characterized
      by the greatest increase in electrical conductivity following Hy-Dh cycles.
      Following Dh 2 and Dh 3, the respiratory activity of Ler seeds significantly
      increased, in contrast to the other ecotypes, indicative of a dramatic shift in
      metabolism. These differences were associated with accession-specific content and
      patterns of change of (i) cell wall-related laminaribiose and mannose; (ii) fatty
      acid composition, specifically of the unsaturated oleic acid and alpha-linoleic
      acid; and (iii) asparagine, ornithine and the related polyamine putrescine.
      Furthermore, in the Ler ecotype the content of the tricarboxylic acid (TCA) cycle
      intermediates fumarate, succinate and malate increased in response to
      dehydration, in contrast to a decrease in the other three ecotypes. These
      findings provide a link between seed respiration, energy metabolism, fatty acid
      beta-oxidation, nitrogen mobilization and membrane permeability and the improved
      germination of Ler seeds following Hy-Dh cycles.

PMID- 22156385
TI  - Intensive decongestive treatment restores ability to work in patients with
      advanced forms of primary and secondary lower extremity lymphoedema.
AB  - OBJECTIVE: To show that adequate therapy for lymphoedema is able to restore
      ability to work. MATERIALS AND METHODS: The population of patients with primary
      lymphoedema registered in the university clinical centre diagnosed with primary
      or secondary lymphoedema and presumed by the national social institution as
      completely unable to work was selected for the retrospective analysis and divided
      into two groups. Group 1 consisted of 25 patients treated with a complex
      decongestive therapy programme daily for 3-6 weeks. The study population
      comprised 19 women and six men from 14 to 61 years of age (mean 31.5). In all 25
      patients, complete inability to work was certified by the social institution
      before the treatment started. Group 2 consisted of 47 patients, 14 men and 33
      women, aged from 26 to 71 years (mean 39 years) treated by so-called standard
      methods, who resigned from the proposed intensive treatment. In all 47 patients,
      complete inability to work was declared by the social institution before the
      treatment. Ability to work and oedema reduction were assessed by the treating
      physician. RESULTS: The intensive phase of treatment succeeded in 3870-15,330 mL
      oedema reduction in Group 1. After the end of therapy, 21 patients were able to
      work or study without any limitation and patients returned to their regular
      professional activity. Among four others, two were on welfare for at least 10
      years, for another one welfare was their only income and one person was receiving
      a social pension. In none of the patients from group 2 was any significant oedema
      reduction observed. Every patient from group 2 maintained the social pension due
      to ineffective treatment. CONCLUSIONS: Complex decongestive therapy is a very
      efficient form of treatment in advanced primary and secondary lymphoedema. It
      allows returning to work after a short period of temporary disability without the
      necessity of a social pension.

PMID- 22156386
TI  - Maternal serum alpha-fetoprotein in normal pregnancy at 11-13 weeks' gestation.
AB  - OBJECTIVE: To establish a reference distribution of maternal serum alpha
      fetoprotein (AFP) at 11-13 weeks' gestation and define the contribution of
      maternal variables that influence the measured concentration of AFP. METHODS:
      Serum concentration of AFP at 11-13 weeks was measured in 1,500 singleton
      pregnancies which were not complicated by hypertensive disorders or diabetes
      mellitus and resulted in the live birth at or after 37 weeks of phenotypically
      normal neonates with birth weights above the 5th and below the 95th percentile.
      Multiple regression analysis was used to account for maternal characteristics
      that influence the measured concentration of AFP and a distribution of log
      multiples of the median (MoM) values was fitted. RESULTS: Log(10) AFP increased
      with gestational age, decreased with maternal weight and was significantly
      affected by maternal racial origin, smoking status and method of conception.
      Compared with values in Caucasian women who were non-smokers and conceived
      spontaneously, AFP MoM was on average 23% higher in Afro-Caribbeans and 8% lower
      in East Asians, 11% higher in smokers and 10% higher in those conceiving by in
      vitro fertilization. CONCLUSION: In normal pregnancies at 11-13 weeks, serum AFP
      increases with gestational age and is affected by maternal race, weight, smoking
      status and method of conception.

PMID- 22156387
TI  - Development of allele-specific primer PCR for a swine TLR2 SNP and comparison of
      the frequency among several pig breeds of Japan and the Czech Republic.
AB  - In the present study, we have developed an allele-specific primer-polymerase
      chain reaction (ASP-PCR) for genotyping a single nucleotide polymorphism (SNP) of
      swine Toll-like receptor 2 (TLR2) (C406G), which is related to the prevalence of
      pneumonia caused by Mycoplasma hyopneumoniae. We also compared the allele
      frequency among several pig breeds of Japan and the Czech Republic. Allele
      specific primers were constructed by introducing 1-base mismatch sequence before
      the SNP site. The swine TLR2 C406G mutation was successfully determined by the
      ASP-PCR using genomic DNA samples in Japan as previously genotyped by a
      sequencing method. Using the PCR condition determined, genomic DNA samples from
      pig blood obtained from 110 pigs from 7 different breeds in the Czech Republic
      were genotyped by the ASP-PCR. The genotyping results from the ASP-PCR were
      completely matched with the results from the sequencing method. The allele
      frequency of the swine TLR2 C406G mutation was 27.5% in the Czech Republic and
      3.6% in Japan. The C406G mutation was only found in the Landrace breed in Japan,
      and was almost exclusively found in the Landrace breed in the Czech Republic as
      well. These results indicated the usefulness of ASP-PCR for detecting a specific
      SNP for swine TLR2.

PMID- 22156388
TI  - Hemangiosarcoma with widespread metastasis that originated on the metatarsal pad
      of a Java sparrow (Padda oryzivora).
AB  - A five-year-old male Java sparrow (Padda oryzivora) was examined because of the
      appearance of a purple spot approximately 1 mm in diameter on the right
      metatarsal pad. Seven months later, the spot spread to the entire right leg, and
      the bird died. At necropsy, multiple neoplastic masses on the right leg reached
      up to the pelvic cavity. There was one similar mass on the right kidney and
      multiple red spots on the liver. Histopathological examination revealed that
      neoplastic cells proliferated solidly or formed abundant irregular blood vessels.
      Watanabe silver staining revealed that neoplastic cells were surrounded by
      argentophil fibers. Immunohistochemically, the neoplastic cells were positive for
      anti-human von Willebrand factor antibodies. This is the first report of
      hemangiosarcoma in a finch.

PMID- 22156389
TI  - Prevalence and mechanism of antimicrobial resistance in Staphylococcus aureus
      isolates from diseased cattle, swine and chickens in Japan.
AB  - Antimicrobial administration is essential for the control and treatment of
      diseases in animals, but the emergence and prevalence of antimicrobial-resistant
      Staphylococcus aureus is a significant concern during animal production. Here we
      investigated the antimicrobial susceptibility of S. aureus from diseased food
      producing animals and molecularly characterized the methicillin-resistant and
      fluoroquinolone-resistant isolates. A total of 290 S. aureus isolates obtained
      from cattle (n=246), swine (n=16), and chickens (n=28) between 2003 and 2009 were
      examined for antimicrobial susceptibility against 9 antimicrobials using an agar
      dilution method. Resistance to penicillin (PC) was most frequently found (24.8%),
      followed by oxytetracycline (OTC, 10.0%), dihydrostreptomycin (4.1%),
      erythromycin (EM, 3.1%), enrofloxacin (ERFX, 2.1%), and kanamycin (1.7%). The PC
      resistance rate was significantly higher in swine than in cattle (P<0.01) and
      chickens (P<0.01). The resistance rates to OTC, EM and ERFX were significantly
      higher in swine and chickens than in cattle (P<0.05). Methicillin-resistant S.
      aureus (MRSA) was recovered from milk derived from a cow with mastitis in 2003;
      sequence type 8, SCCmec type IV and spa type t024. In the six ERFX-resistant
      strains isolated after 2003, amino acid substitutions in ParC with/without GyrA
      were detected. As the prevalence of MRSA and FQ-resistant S. aureus in the
      animals should be noticed, continuous monitoring is necessary to control
      resistance to clinically important antimicrobials in S. aureus from food
      producing animals.

PMID- 22156390
TI  - High-grade myofibroblastic sarcoma of inguinal region in a dog.
AB  - A subcutaneous tumor in the left inguinal region was present in an 11-year-old
      female bloodhound. Histopathologically, the tumor showed invasive growth and
      extensive necroses, and it was composed of spindle-shaped, elongated, and
      stellate neoplastic cells accompanied by occasional giant cells arranged in
      fascicular, herringbone, or irregular storiform patterns with abundant production
      of collagen fibers. The cytoplasm of most tumor cells was positive for vimentin,
      alpha-smooth muscle actin, and calponin, but was negative for desmin, smoothelin,
      and S-100. Furthermore, most of the tumor cells were negative for Iba1 while some
      tumor cells were weakly positive. Thus, this tumor was diagnosed as a high-grade
      myofibroblastic sarcoma according to the diagnostic criteria for human
      myofibroblastic sarcomas.

PMID- 22156391
TI  - Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and
      pharmacological suppression.
AB  - In yeast, chronological senescence (CS) is defined as loss of viability in
      stationary culture. Although its relevance to the organismal aging remained
      unclear, yeast CS was one of the most fruitful models in aging research. Here we
      described a mammalian replica of yeast CS: loss of viability of overgrown
      "yellow" cancer cell culture. In a density and time (chronological)-dependent
      manner, cell culture loses the ability to re-grow in fresh medium. Rapamycin
      dramatically decelerated CS. Loss of viability was caused by acidification of the
      medium by lactic acid (lactate). Rapamycin decreased production of lactate,
      making conditioned medium (CM) less deadly. Both deadly CM and lactate caused
      loss of viability in low cell density, not preventable by either rapamycin or
      additional glucose. Also, NAC, LY294002, U0126, GSK733, which all indirectly
      inhibit mTOR and have been shown to suppress the senescent phenotype in
      traditional models of mammalian cell senescence, also decreased lactate
      production and decelerated CS. We discuss that although CS does not mimic
      organismal aging, the same signal transduction pathways that drive CS also drive
      aging.

PMID- 22156392
TI  - Phase I/II study of preoperative concurrent chemoradiotherapy with S-1 for
      locally advanced, resectable rectal adenocarcinoma.
AB  - PURPOSE: To assess the maximum tolerability of a combination of S-1 and
      preoperative radiotherapy and to evaluate the feasibility and activity in
      patients with locally advanced rectal cancer. METHODS: Patients (n = 30) with
      adenocarcinoma of the middle or lower rectum were enrolled in a phase I (n = 9)
      and/or phase II (n = 21) trial. A total dose of 45 Gy was delivered in 25
      fractions over 5 weeks, and S-1 was orally administered twice a day on days 1-14
      and 22-35. Surgical resection was scheduled 4-8 weeks after the completion of
      chemoradiation. RESULTS: In phase I, the recommended dose (RD) of S-1 was 80
      mg/m(2)/day, and the maximum-tolerated dose was never reached. A total of 27
      cases, including the 6 RD cases in phase I, were enrolled in phase II. In phase
      II, a pathological complete response (pCR) was observed in 6/27 patients (22%),
      pathological downstaging was observed in 21/27 patients (78%), and a tumor volume
      reduction of 69 +/- 22% was obtained. These results were similar to the
      previously reported pCR rates of 16-18%, pathological downstaging rates of 49
      59%, and tumor volume reduction of 68% after chemoradiotherapy with capecitabine.
      Grade 3 adverse events consisted of one case of leukopenia (4%), 2 cases of
      anemia (7%) and 3 cases of diarrhea (11%). Overall, the adverse events were very
      mild. Hand-foot syndrome was not observed. CONCLUSION: The efficacy of
      chemoradiotherapy with S-1 seems to be equivalent to the efficacy reported for
      chemoradiotherapy with capecitabine, but the adverse events were much milder,
      although further study is warranted.

PMID- 22156394
TI  - Complete resequencing and reannotation of the Lactobacillus plantarum WCFS1
      genome.
AB  - There is growing interest in the beneficial effects of Lactobacillus plantarum on
      human health. The genome of L. plantarum WCFS1, first sequenced in 2001, was
      resequenced using Solexa technology. We identified 116 nucleotide corrections and
      improved function prediction for nearly 1,200 proteins, with a focus on metabolic
      functions and cell surface-associated proteins.

PMID- 22156395
TI  - Complete genome sequence of Pelagibacterium halotolerans B2(T).
AB  - Pelagibacterium halotolerans B2(T) is a marine halotolerant bacterium that was
      isolated from a seawater sample collected from the East China Sea. Here, we
      present the complete genome sequence of the type strain P. halotolerans B2(T),
      which consists of one chromosome (3,944,837 bp; 61.4% G+C content) and one
      plasmid (4,050 bp; 56.1% G+C content). This is the first complete genome of a
      member of the Pelagibacterium genus.

PMID- 22156396
TI  - Draft genome sequence of Halomonas sp. strain HAL1, a moderately halophilic
      arsenite-oxidizing bacterium isolated from gold-mine soil.
AB  - We report the draft genome sequence of arsenite-oxidizing Halomonas sp. strain
      HAL1, isolated from the soil of a gold mine. Genes encoding proteins involved in
      arsenic resistance and transformation, phosphate utilization and uptake, and
      betaine biosynthesis were identified. Their identification might help in
      understanding how arsenic and phosphate metabolism are intertwined.

PMID- 22156397
TI  - Draft genome sequence of Novosphingobium nitrogenifigens Y88(T).
AB  - Novosphingobium nitrogenifigens was originally isolated from pulp and paper mill
      wastewater, a low-nitrogen, high-carbon environment. N. nitrogenifigens is the
      first known nitrogen-fixing, polyhydroxyalkanoate-accumulating sphingomonad, and
      we report the annotated draft genome sequence of the type strain Y88(T) here.

PMID- 22156398
TI  - Genome sequence of Propionibacterium acnes type II strain ATCC 11828.
AB  - Propionibacterium acnes is an anaerobic Gram-positive bacterium that forms part
      of the normal human cutaneous microbiota and is occasionally associated with
      inflammatory diseases (I. Kurokawa et al., Exp. Dermatol. 18:821-832, 2009). Here
      we present the complete genome sequence for the commercially available P. acnes
      type II reference strain ATCC 11828 (I. Nagy et al., Microbes Infect. 8:2195
      2205, 2006) recovered from a subcutaneous abscess.

PMID- 22156399
TI  - Draft genome sequence of an Acinetobacter genomic species 3 strain harboring a
      bla(NDM-1) gene.
AB  - Here we report the draft genome sequence of one Acinetobacter genomic species 3
      strain, D499, which harbors the bla(NDM-1) gene. The total length of the
      assembled genome is 4,103,824 bp, and 3,896 coding sequences (CDSs) were
      predicted within the genome. A previously unreported bla(NDM-1)-bearing plasmid
      was identified in this strain.

PMID- 22156400
TI  - Mechanism and genotype-phenotype correlation of two proximal 6q deletions
      characterized using mBAND, FISH, array CGH, and DNA sequencing.
AB  - Proximal 6q deletions have a milder phenotype than middle and distal 6q
      deletions. We describe 2 patients with non-overlapping deletions of about 15 and
      19 Mb, respectively, which subdivide the proximal 6q region into 2 parts. The
      aberrations were identified using karyotyping and analysed using mBAND and array
      CGH. The unaffected mother of the first patient carried a mosaic karyotype with
      the deletion in all metaphases analysed and a small supernumerary marker formed
      by the deleted material in about 77% of cells. Her chromosome 6 centromeric
      signal was split between the deleted chromosome and the marker, suggesting that
      this deletion arose through the centromere fission mechanism. In this family the
      location of the proximal breakpoint in the centromere prevented cloning of the
      deletion junction, but the junction of the more distal deletion in the second
      patient was cloned and sequenced. This analysis showed that the latter aberration
      was most likely caused by non-homologous end joining. The second patient also had
      a remarkably more severe phenotype which could indicate a partial overlap of his
      deletion with the middle 6q interval. The phenotypes of both patients could be
      partly correlated with the gene content of their deletions and with phenotypes of
      other published patients.

PMID- 22156401
TI  - Unrestricted quality of seeds in European broad-leaved tree species growing at
      the cold boundary of their distribution.
AB  - BACKGROUND AND AIMS: The low-temperature range limit of tree species may be
      determined by their ability to produce and disperse viable seeds. Biological
      processes such as flowering, pollen transfer, pollen tube growth, fertilization,
      embryogenesis and seed maturation are expected to be affected by cold
      temperatures. The aim of this study was to assess the quality of seeds of nine
      broad-leaved tree species close to their elevational limit. METHODS: We studied
      nine, mostly widely distributed, European broad-leaved tree species in the genera
      Acer, Fagus, Fraxinus, Ilex, Laburnum, Quercus, Sorbus and Tilia. For each
      species, seeds were collected from stands close to optimal growth conditions (low
      elevation) and from marginal stands (highest elevation), replicated in two
      regions in the Swiss Alps. Measurements included seed weight, seed size, storage
      tissue quality, seed viability and germination success. KEY RESULTS: All species
      examined produced a lot of viable seeds at their current high-elevation range
      limit during a summer ranked 'normal' by long-term temperature records. Low- and
      high-elevation seed sources showed hardly any trait differences. The
      concentration of non-structural carbohydrates tended to be higher at high
      elevation. Additionally, in one species, Sorbus aucuparia, all measured traits
      showed significantly higher seed quality in high-elevation seed sources.
      CONCLUSIONS: For the broad-leaved tree taxa studied, the results are not in
      agreement with the hypothesis of reduced quality of seeds in trees at their high
      elevation range limits. Under the current climatic conditions, seed quality does
      not constitute a serious constraint in the reproduction of these broad-leaved
      tree species at their high-elevation limit.

PMID- 22156404
TI  - Configuring robust DNA strand displacement reactions for in situ molecular
      analyses.
AB  - The number of distinct biomolecules that can be visualized within individual
      cells and tissue sections via fluorescence microscopy is limited by the spectral
      overlap of the fluorescent dye molecules that are coupled permanently to their
      targets. This issue prohibits characterization of important functional
      relationships between different molecular pathway components in cells. Yet,
      recent improved understandings of DNA strand displacement reactions now provides
      opportunities to create programmable labeling and detection approaches that
      operate through controlled transient interactions between different dynamic DNA
      complexes. We examined whether erasable molecular imaging probes could be created
      that harness this mechanism to couple and then remove fluorophore-bearing
      oligonucleotides to and from DNA-tagged protein markers within fixed cell
      samples. We show that the efficiency of marker erasing via strand displacement
      can be limited by non-toehold mediated stand exchange processes that lower the
      rates that fluorophore-bearing strands diffuse out of cells. Two probe
      constructions are described that avoid this problem and allow efficient
      fluorophore removal from their targets. With these modifications, we show one can
      at least double the number of proteins that can be visualized on the same cells
      via reiterative in situ labeling and erasing of markers on cells.

PMID- 22156405
TI  - Increased cardiovascular and renal disease but not reduced life expectancy among
      diabetic participants in the general Northern Greek population.
AB  - We compared life expectancy and causes of death based on death certificates of
      269 diabetic participants (group A) and 5659 nondiabetic participants (group B)
      who died from January 1, 1991 to December 31, 2010, in 3 small towns of Northern
      Greece. Age at death was significantly (P = .011) higher in group A (77.2 +/- 8.7
      years) than in group B (75.7 +/- 18.9 years). Males with diabetes lived longer
      with a mean difference of 4.7 (2.8-6.6) years (P < .001), whereas females without
      diabetes lived longer, with a mean difference of 2.3 (1.1-5.6) years (P = .004).
      Diabetic participants died more frequently of myocardial infarction (P = .001),
      chronic renal failure (P < .001), followed by pneumonia (P = .010) and
      hyperosmolar non-ketotic coma (P < .001). Nondiabetic participants died more
      frequently of lung cancer (P < .001), old age (P < .001), and car accidents (P =
      .004). In conclusion, the cardiovascular and renal disease burden among diabetic
      participants did not reduce life expectancy, especially in men.

PMID- 22156406
TI  - Prognostic value of NT-proBNP at rest and peak exercise in patients with impaired
      left ventricular function.
AB  - We aimed to identify whether N-terminal fragment of pro-brain natriuretic peptide
      (NT-proBNP) at peak exercise can provide incremental clinical information over
      resting levels. A total of 90 patients with systolic heart failure were
      prospectively studied. Levels of plasma NT-proBNP were assessed at rest and at
      peak exercise during a cardiopulmonary exercise test. Patients were followed-up
      for 30 +/- 10 months. Levels of NT-proBNP at baseline and peak exercise were
      significantly correlated with left ventricular ejection fraction ([LVEF] r = 
      .629, P < .001 and r = -.630, P < .001, respectively) and peak oxygen uptake ([Vo
      (2)] r = -.752, P < .001 and r = -.740, P < .001, respectively). Levels of plasma
      NT-proBNP at peak exercise demonstrated similar predictive ability for the
      detection of patients with low peak Vo (2) and LVEF <28%. Levels of plasma NT
      proBNP can detect low-functional class patients and patients who may be the
      candidates for heart transplantation with high sensitivity and specificity. At
      baseline and peak exercise, NT-proBNP demonstrates similar prognostic and
      predictive ability.

PMID- 22156407
TI  - Arthrogryposis multiplex congenita and Pena-Shokeir phenotype: challenge of
      prenatal diagnosis--report of 21 cases, antenatal findings and review.
AB  - OBJECTIVE: To elaborate the antenatal sonographic findings of fetuses with the
      suspicion of fetal akinesia, thereby focusing on the accuracy of prenatal
      differentiation between subtypes of fetal akinesia, namely Pena-Shokeir phenotype
      (PSP) and arthrogryposis multiplex congenita (AMC). METHODS: We herein present
      our experience of 21 patients with PSP and AMC diagnosed antenatally at a
      tertiary prenatal referral center. During the study period 30,485 consecutive
      high- and low-risk pregnancies were examined. The prenatal sonograms, pediatric
      charts and autopsy data of affected individuals were reviewed. Our findings were
      analyzed together with findings retrieved from the literature. RESULTS: The
      diagnosis of AMC has been established between 12+0 and 30+1 gestational weeks,
      whereas cases found to have PSP were all diagnosed in advanced pregnancy. In
      accordance to previous findings, our data suggest that pulmonary hypoplasia is
      obligatory in PSP and cannot be found in AMC. Therefore, all pregnancies (9/9)
      affected by PSP were terminated on parental request. Of those fetuses with AMC,
      3/12 were liveborn, 2 of which have neuromotoric disabilities. CONCLUSIONS:
      Establishing the correct prenatal diagnosis of PSP and AMC at an early stage and
      its diligent prognostic evaluation play a crucial role in order to provide
      adequate advice to the afflicted parents and to enable appropriate intervention
      at an early stage.

PMID- 22156408
TI  - Chronological lifespan in stationary culture: from yeast to human cells.

PMID- 22156409
TI  - Recollection of the early years of the research on cytochrome P450.
AB  - Since the publication of the first paper on "cytochrome P450" in 1962, the
      biochemical research on this novel hemoprotein expanded rapidly in the 1960s and
      the 1970s as its principal roles in various important metabolic processes
      including steroid hormone biosynthesis in the steroidogenic organs and drug
      metabolism in the liver were elucidated. Establishment of the purification
      procedures of microsomal and mitochondrial P450s in the middle of the 1970s
      together with the introduction of molecular biological techniques accelerated the
      remarkable expansion of the research on P450 in the following years. This review
      paper summarizes the important developments in the research on P450 in the early
      years, for about two decades from the beginning, together with my personal
      recollections.

PMID- 22156410
TI  - Alteration in the plasma concentration of a DAAO inhibitor, 3-methylpyrazole-5
      carboxylic acid, in the ketamine-treated rats and the influence on the
      pharmacokinetics of plasma D-tryptophan.
AB  - A determination method for 3-methylpyrazole-5-carboxylic acid (MPC), an inhibitor
      of D-amino acid oxidase (DAAO), in rat plasma was developed by using high
      performance liquid chromatography-mass spectrometry (LC-MS). The structural
      isomer of MPC, 3-methylpyrazole-4-carboxylic acid, was used as an internal
      standard, and the intra- and inter-day accuracies and precisions were
      satisfactory for the determination of plasma MPC.Next, the LC-MS method was
      applied to determine the plasma MPC concentration in ketamine (Ket)-treated rats
      after intraperitoneal administration of MPC (5.0 or 50 mg.kg(-1)). The C(max)
      value of plasma MPC concentration in the Ket-treated rats was significantly
      higher than that in the control group when a high dose of MPC (50 mg.kg(-1)) was
      administered. In addition, it was found that plasma D-tryptophan (D-Trp)
      concentration in Ket-treated rats administered D-Trp was not significantly
      increased by MPC, suggesting that the DAAO-inhibitory effect of MPC is attenuated
      in Ket-treated rats.

PMID- 22156411
TI  - Decreased xylitol formation during xylose fermentation in Saccharomyces
      cerevisiae due to overexpression of water-forming NADH oxidase.
AB  - The recombinant xylose-fermenting Saccharomyces cerevisiae strain harboring
      xylose reductase (XR) and xylitol dehydrogenase (XDH) from Scheffersomyces
      stipitis requires NADPH and NAD(+), creates cofactor imbalance, and causes
      xylitol accumulation during growth on d-xylose. To solve this problem, noxE,
      encoding a water-forming NADH oxidase from Lactococcus lactis driven by the PGK1
      promoter, was introduced into the xylose-utilizing yeast strain KAM-3X. A
      cofactor microcycle was set up between the utilization of NAD(+) by XDH and the
      formation of NAD(+) by water-forming NADH oxidase. Overexpression of noxE
      significantly decreased xylitol formation and increased final ethanol production
      during xylose fermentation. Under xylose fermentation conditions with an initial
      d-xylose concentration of 50 g/liter, the xylitol yields for of KAM-3X(pPGK1
      noxE) and control strain KAM-3X were 0.058 g/g xylose and 0.191 g/g,
      respectively, which showed a 69.63% decrease owing to noxE overexpression; the
      ethanol yields were 0.294 g/g for KAM-3X(pPGK1-noxE) and 0.211 g/g for the
      control strain KAM-3X, which indicated a 39.33% increase due to noxE
      overexpression. At the same time, the glycerol yield also was reduced by 53.85%
      on account of the decrease in the NADH pool caused by overexpression of noxE.

PMID- 22156412
TI  - Potential probiotic Kluyveromyces marxianus B0399 modulates the immune response
      in Caco-2 cells and peripheral blood mononuclear cells and impacts the human gut
      microbiota in an in vitro colonic model system.
AB  - Considering the increase in the consumption of yeasts as human probiotics, the
      aim of this study was to broadly investigate the beneficial properties of the
      lactic yeast Kluyveromyces marxianus (formerly Kluyveromyces fragilis) B0399.
      Several potential probiotic traits of K. marxianus B0399 were investigated by
      using in vitro assays, including adhesion and immune modulation, and the effect
      of the administration of 10(7) CFU/day of K. marxianus B0399 on the composition
      and metabolic activity of the human intestinal microbiota was investigated in a 3
      stage continuous-culture system simulating the human colon. We demonstrated that
      this strain was highly adhesive to human enterocyte-like Caco-2 cells and
      modulated the immune response, inducing proinflammatory cytokines in peripheral
      blood mononuclear cells (PBMCs). In the presence of inflammatory stimulation with
      lipopolysaccharide (LPS), K. marxianus B0399 provoked decreases in the levels of
      production of proinflammatory cytokines in PBMCs and Caco-2 cells, thus
      ameliorating the inflammatory response. Furthermore, K. marxianus B0399 impacted
      the colonic microbiota, increasing the bifidobacterial concentration in the
      stages of the colonic model system simulating the proximal and transverse colon.
      The amounts of the short-chain fatty acids acetate and propionate also increased
      following yeast supplementation. Finally, K. marxianus B0399 was found to induce
      a decrease of the cytotoxic potential of the culture supernatant from the first
      stage of the colonic model system. The effects of K. marxianus B0399 on adhesion,
      immune function, and colonic microbiota demonstrate that this strain possesses a
      number of beneficial and strain-specific properties desirable for a microorganism
      considered for application as a probiotic.

PMID- 22156413
TI  - The allele-specific probe and primer amplification assay, a new real-time PCR
      method for fine quantification of single-nucleotide polymorphisms in pooled DNA.
AB  - The evolution of fungicide resistance within populations of plant pathogens must
      be monitored to develop management strategies. Such monitoring often is based on
      microbiological tests, such as microtiter plate assays. Molecular monitoring
      methods can be considered if the mutations responsible for resistance have been
      identified. Allele-specific real-time PCR approaches, such as amplification
      refractory mutation system (ARMS) PCR and mismatch amplification mutation assay
      (MAMA) PCR, are, despite their moderate efficacy, among the most precise methods
      for refining SNP quantification. We describe here a new real-time PCR method, the
      allele-specific probe and primer amplification assay (ASPPAA PCR). This method
      makes use of mixtures of allele-specific minor groove binder (MGB) TaqMan probes
      and allele-specific primers for the fine quantification of SNPs from a pool of
      DNA extracted from a mixture of conidia. It was developed for a single-nucleotide
      polymorphism (SNP) that is responsible for resistance to the sterol biosynthesis
      inhibitor fungicide fenhexamid, resulting in the replacement of the phenylalanine
      residue (encoded by the TTC codon) in position 412 of the enzymatic target (3
      ketoreductase) by a serine (TCC), valine (GTC), or isoleucine (ATC) residue. The
      levels of nonspecific amplification with the ASPPAA PCR were reduced at least
      four times below the level of currently available allele-specific real-time PCR
      approaches due to strong allele specificity in amplification cycles, including
      two allele selectors. This new method can be used to quantify a complex
      quadriallelic SNP in a DNA pool with a false discovery rate of less than 1%.

PMID- 22156414
TI  - Lactic acid bacterium and yeast microbiotas of 19 sourdoughs used for
      traditional/typical italian breads: interactions between ingredients and
      microbial species diversity.
AB  - The study of the microbiotas of 19 Italian sourdoughs used for the manufacture of
      traditional/typical breads allowed the identification, through a culture
      dependent approach, of 20 and 4 species of lactic acid bacteria (LAB) and yeasts,
      respectively. Numerically, the most frequent LAB isolates were Lactobacillus
      sanfranciscensis (ca. 28% of the total LAB isolates), Lactobacillus plantarum
      (ca. 16%), and Lactobacillus paralimentarius (ca. 14%). Saccharomyces cerevisiae
      was identified in 16 sourdoughs. Candida humilis, Kazachstania barnettii, and
      Kazachstania exigua were also identified. As shown by principal component
      analysis (PCA), a correlation was found between the ingredients, especially the
      type of flour, the microbial community, and the biochemical features of
      sourdoughs. Triticum durum flours were characterized by the high level of
      maltose, glucose, fructose, and free amino acids (FAA) correlated with the sole
      or main presence of obligately heterofermentative LAB, the lowest number of
      facultatively heterofermentative strains, and the low cell density of yeasts in
      the mature sourdoughs. This study highlighted, through a comprehensive and
      comparative approach, the dominant microbiotas of 19 Italian sourdoughs, which
      determined some of the peculiarities of the resulting traditional/typical Italian
      breads.

PMID- 22156415
TI  - Discovering novel bile protection systems in Bifidobacterium breve UCC2003
      through functional genomics.
AB  - Tolerance of gut commensals to bile salt exposure is an important feature for
      their survival in and colonization of the intestinal environment. A
      transcriptomic approach was employed to study the response of Bifidobacterium
      breve UCC2003 to bile, allowing the identification of a number of bile-induced
      genes with a range of predicted functions. The potential roles of a selection of
      these bile-inducible genes in bile protection were analyzed following
      heterologous expression in Lactococcus lactis. Genes encoding three transport
      systems belonging to the major facilitator superfamily (MFS), Bbr_0838, Bbr_0832,
      and Bbr_1756, and three ABC-type transporters, Bbr_0406-0407, Bbr_1804-1805, and
      Bbr_1826-1827, were thus investigated and shown to provide enhanced resistance
      and survival to bile exposure. This work significantly improves our understanding
      as to how bifidobacteria respond to and survive bile exposure.

PMID- 22156416
TI  - Identification and characterization of the LysR-type transcriptional regulator
      HsdR for steroid-inducible expression of the 3alpha-hydroxysteroid
      dehydrogenase/carbonyl reductase gene in Comamonas testosteroni.
AB  - 3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) from
      Comamonas testosteroni is a key enzyme in steroid degradation in soil and water.
      3alpha-HSD/CR gene (hsdA) expression can be induced by steroids like testosterone
      and progesterone. Previously, we have shown that the induction of hsdA expression
      by steroids is a derepression where steroidal inducers bind to two repressors,
      RepA and RepB, thereby preventing the blocking of hsdA transcription and
      translation, respectively (G. Xiong and E. Maser, J. Biol. Chem. 276:9961-9970,
      2001; G. Xiong, H. J. Martin, and E. Maser, J. Biol. Chem. 278:47400-47407,
      2003). In the present study, a new LysR-type transcriptional factor, HsdR, for
      3alpha-HSD/CR expression in C. testosteroni has been identified. The hsdR gene is
      located 2.58 kb downstream from hsdA on the C. testosteroni ATCC 11996 chromosome
      with an orientation opposite that of hsdA. The hsdR gene was cloned and
      recombinant HsdR protein was produced, as was anti-HsdR polyclonal antibodies.
      While heterologous transformation systems revealed that HsdR activates the
      expression of the hsdA gene, electrophoresis mobility shift assays showed that
      HsdR specifically binds to the hsdA promoter region. Interestingly, the activity
      of HsdR is dependent on decreased repression by RepA. Furthermore, in vitro
      binding assays indicated that HsdR can come into contact with RNA polymerase. As
      expected, an hsdR knockout mutant expressed low levels of 3alpha-HSD/CR compared
      to that of wild-type C. testosteroni after testosterone induction. In conclusion,
      HsdR is a positive transcription factor for the hsdA gene and promotes the
      induction of 3alpha-HSD/CR expression in C. testosteroni.

PMID- 22156417
TI  - Effects of temperature, relative humidity, absolute humidity, and evaporation
      potential on survival of airborne Gumboro vaccine virus.
AB  - Survival of airborne virus influences the extent of disease transmission via air.
      How environmental factors affect viral survival is not fully understood. We
      investigated the survival of a vaccine strain of Gumboro virus which was
      aerosolized at three temperatures (10 degrees C, 20 degrees C, and 30 degrees C)
      and two relative humidities (RHs) (40% and 70%). The response of viral survival
      to four metrics (temperature, RH, absolute humidity [AH], and evaporation
      potential [EP]) was examined. The results show a biphasic viral survival at 10
      degrees C and 20 degrees C, i.e., a rapid initial inactivation in a short period
      (2.3 min) during and after aerosolization, followed by a slow secondary
      inactivation during a 20-min period after aerosolization. The initial decays of
      aerosolized virus at 10 degrees C (1.68 to 3.03 ln % min(-1)) and 20 degrees C
      (3.05 to 3.62 ln % min(-1)) were significantly lower than those at 30 degrees C
      (5.67 to 5.96 ln % min(-1)). The secondary decays at 10 degrees C (0.03 to 0.09
      ln % min(-1)) tended to be higher than those at 20 degrees C (-0.01 to 0.01 ln %
      min(-1)). The initial viral survival responded to temperature and RH and
      potentially to EP; the secondary viral survival responded to temperature and
      potentially to RH. In both phases, survival of the virus was not significantly
      affected by AH. These findings suggest that long-distance transmission of
      airborne virus is more likely to occur at 20 degrees C than at 10 degrees C or 30
      degrees C and that current Gumboro vaccination by wet aerosolization in poultry
      industry is not very effective due to the fast initial decay.

PMID- 22156418
TI  - Molecular and histological characterization of primary (betaproteobacteria) and
      secondary (gammaproteobacteria) endosymbionts of three mealybug species.
AB  - Microscopic localization of endosymbiotic bacteria in three species of mealybug
      (Pseudococcus longispinus, the long-tailed mealybug; Pseudococcus calceolariae,
      the citrophilus mealybug; and Pseudococcus viburni, the obscure mealybug) showed
      these organisms were confined to bacteriocyte cells within a bacteriome centrally
      located within the hemocoel. Two species of bacteria were present, with the
      secondary endosymbiont, in all cases, living within the primary endosymbiont. DNA
      from the dissected bacteriomes of all three species of mealybug was extracted for
      analysis. Sequence data from selected 16S rRNA genes confirmed identification of
      the primary endosymbiont as "Candidatus Tremblaya princeps," a
      betaproteobacterium, and the secondary endosymbionts as gammaproteobacteria
      closely related to Sodalis glossinidius. A single 16S rRNA sequence of the
      primary endosymbiont was found in all individuals of each mealybug species. In
      contrast, the presence of multiple divergent strains of secondary endosymbionts
      in each individual mealybug suggests different evolutionary and transmission
      histories of the two endosymbionts. Mealybugs are known vectors of the plant
      pathogen Grapevine leafroll-associated virus 3. To examine the possible role of
      either endosymbiont in virus transmission, an extension of the model for
      interaction of proteins with bacterial chaperonins, i.e., GroEL protein homologs,
      based on mobile-loop amino acid sequences of their GroES homologs, was developed
      and used for analyses of viral coat protein interactions. The data from this
      model are consistent with a role for the primary endosymbiont in mealybug
      transmission of Grapevine leafroll-associated virus 3.

PMID- 22156419
TI  - Activation-independent cyclization of monoterpenoids.
AB  - The biosynthesis of cyclic monoterpenes (C(10)) generally requires the
      cyclization of an activated linear precursor (geranyldiphosphate) by specific
      terpene cyclases. Cyclic triterpenes (C(30)), on the other hand, originate from
      the linear precursor squalene by the action of squalene-hopene cyclases (SHCs) or
      oxidosqualene cyclases (OSCs). Here, we report a novel terpene cyclase from
      Zymomonas mobilis (ZMO1548-Shc) with the unique capability to cyclize citronellal
      to isopulegol. To our knowledge, ZMO1548-Shc is the first biocatalyst with
      diphosphate-independent monoterpenoid cyclase activity. A combinatorial approach
      using site-directed mutagenesis and modeling of the active site with a bound
      substrate revealed that the cyclization of citronellal proceeds via a different
      mechanism than that of the cyclization of squalene.

PMID- 22156420
TI  - Absence of livestock-associated methicillin-resistant staphylococcus aureus
      clonal complex CC398 as a nasal colonizer of pigs raised in an alternative
      system.
AB  - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) ST398
      isolated from pigs raised in conventional farms was previously reported. Here we
      report a study on 25 farms adhering to an alternative system. LA-MRSA ST398 was
      not detected in nasal swabs from 178 pigs or from 89 humans working and living on
      these farms.

PMID- 22156421
TI  - Carbapenem-hydrolyzing GES-5-encoding gene on different plasmid types recovered
      from a bacterial community in a sewage treatment plant.
AB  - Plasmids pRSB113 and pRSB115 were recovered from an activated sludge bacterial
      community of a municipal wastewater treatment plant in Germany. Both plasmids
      carry the same bla(GES-5) carbapenemase gene, located within two distinct class 1
      integrons. These plasmids have different backbones, belong to different
      incompatibility groups, and could replicate in both Pseudomonas aeruginosa and
      Escherichia coli.

PMID- 22156423
TI  - Effect of Rj genotype and cultivation temperature on the community structure of
      soybean-nodulating bradyrhizobia.
AB  - The nodulation tendency and community structure of indigenous bradyrhizobia on Rj
      genotype soybean cultivars at cultivation temperatures of 33/28 degrees C, 28/23
      degrees C, and 23/18 degrees C for 16/8 h (day/night degrees, hours) were
      investigated using 780 bradyrhizobial DNA samples from an Andosol with 13 soybean
      cultivars of four Rj genotypes (non-Rj, Rj(2)Rj(3), Rj(4), and Rj(2)Rj(3)Rj(4)).
      A dendrogram was constructed based on restriction fragment length polymorphism of
      the PCR products (PCR-RFLP) of the 16S-23S rRNA gene internal transcribed spacer
      region. Eleven Bradyrhizobium U.S. Department of Agriculture strains were used as
      a reference. The dendrogram indicated seven clusters based on similarities among
      the reference strains. The occupancy rate of the Bj123 cluster decreased with
      increasing cultivation temperature, whereas the occupancy rates of the Bj110
      cluster, Be76 cluster, and Be94 cluster increased with increasing cultivation
      temperature. In particular, the Rj(2)Rj(3)Rj(4) genotype soybeans were infected
      with a number of Bj110 clusters, regardless of the increasing cultivation
      temperature, compared to other Rj genotype soybean cultivars. The ratio of beta
      diversity to gamma diversity (H'(beta)/H'(gamma)), which represents differences
      in the bradyrhizobial communities by pairwise comparison among cultivation
      temperature sets within the same soybean cultivar, indicated that the
      bradyrhizobial communities tended to be different among cultivation temperatures.
      Multidimensional scaling analysis indicated that the infection of the Bj110
      cluster and the Bj123 cluster by host soybean genotype and the cultivation
      temperature affected the bradyrhizobial communities. These results suggested that
      the Rj genotypes and cultivation temperatures affected the nodulation tendency
      and community structures of soybean-nodulating bradyrhizobia.

PMID- 22156422
TI  - Multiplex PCR-based reverse line blot assay for simultaneous detection of 22
      virulence genes in uropathogenic Escherichia coli.
AB  - Urinary tract infections (UTIs) are among the most common bacterial infections
      and are responsible for significant morbidity and health care costs worldwide.
      The main bacterial cause of uncomplicated UTI is Escherichia coli, which
      possesses numerous virulence factors (VFs). Many studies of the pathogenesis of
      E. coli UTI have centered on VF genes. Hence, the development of better molecular
      assays to study VF genes would facilitate these studies. We developed a highly
      sensitive and specific multiplex PCR-based reverse line blot (mPCR/RLB) assay to
      simultaneously detect 22 VF genes of uropathogenic E. coli and then used it to
      characterize 180 isolates from nonpregnant women of child-bearing age with
      cystitis and 153 fecal isolates from similar-age healthy women, in regional New
      South Wales, Australia. The assay accurately identified all VF genes (of the 22
      under study) known to be present in 30 previously characterized control strains.
      The detection limits were 28 ng of DNA from E. coli isolates and 50 CFU/ml in
      mock-infected urine specimens containing known concentrations of E. coli.
      Cystitis isolates (compared to the fecal isolates) showed a significantly higher
      prevalence of 18 individual VF genes and contained significantly more VF genes
      per isolate (median number, 18.5 versus 6.5 [P = 0.001]). Discordance between
      paired probes for a given VF gene occurred in several clinical test isolates but
      no reference strains and among the test isolates was associated with fecal source
      (10% of VF genes versus 2% for cystitis isolates [P < 0.001]). This novel
      mPCR/RLB method is a potentially powerful tool for investigating the prevalence
      and distribution of VFs in E. coli.

PMID- 22156424
TI  - Requirement for RNA helicase CsdA for growth of Yersinia pseudotuberculosis
      IP32953 at low temperatures.
AB  - The expression of csdA, encoding an RNA helicase, was induced at 3 degrees C in
      Yersinia pseudotuberculosis. The role of CsdA in Y. pseudotuberculosis under cold
      conditions was confirmed by impaired growth of insertional csdA mutants at 3
      degrees C. The results suggest that CsdA is crucial for Y. pseudotuberculosis
      survival in the chilled food chain.

PMID- 22156425
TI  - Cloning and characterization of the polyether salinomycin biosynthesis gene
      cluster of Streptomyces albus XM211.
AB  - Salinomycin is widely used in animal husbandry as a food additive due to its
      antibacterial and anticoccidial activities. However, its biosynthesis had only
      been studied by feeding experiments with isotope-labeled precursors. A strategy
      with degenerate primers based on the polyether-specific epoxidase sequences was
      successfully developed to clone the salinomycin gene cluster. Using this
      strategy, a putative epoxidase gene, slnC, was cloned from the salinomycin
      producer Streptomyces albus XM211. The targeted replacement of slnC and
      subsequent trans-complementation proved its involvement in salinomycin
      biosynthesis. A 127-kb DNA region containing slnC was sequenced, including genes
      for polyketide assembly and release, oxidative cyclization, modification, export,
      and regulation. In order to gain insight into the salinomycin biosynthesis
      mechanism, 13 gene replacements and deletions were conducted. Including slnC, 7
      genes were identified as essential for salinomycin biosynthesis and putatively
      responsible for polyketide chain release, oxidative cyclization, modification,
      and regulation. Moreover, 6 genes were found to be relevant to salinomycin
      biosynthesis and possibly involved in precursor supply, removal of aberrant
      extender units, and regulation. Sequence analysis and a series of gene
      replacements suggest a proposed pathway for the biosynthesis of salinomycin. The
      information presented here expands the understanding of polyether biosynthesis
      mechanisms and paves the way for targeted engineering of salinomycin activity and
      productivity.

PMID- 22156426
TI  - Establishing equivalence for microbial-growth-inhibitory effects ("iso-hurdle
      rules") by analyzing disparate listeria monocytogenes data with a gamma-type
      predictive model.
AB  - Preservative factors act as hurdles against microorganisms by inhibiting their
      growth; these are essential control measures for particular food-borne pathogens.
      Different combinations of hurdles can be quantified and compared to each other in
      terms of their inhibitory effect ("iso-hurdle"). We present here a methodology
      for establishing microbial iso-hurdle rules in three steps: (i) developing a
      predictive model based on existing but disparate data sets, (ii) building an
      experimental design focused on the iso-hurdles using the model output, and (iii)
      validating the model and the iso-hurdle rules with new data. The methodology is
      illustrated with Listeria monocytogenes. Existing data from industry, a public
      database, and the literature were collected and analyzed, after which a total of
      650 growth rates were retained. A gamma-type model was developed for the factors
      temperature, pH, a(w), and acetic, lactic, and sorbic acids. Three iso-hurdle
      rules were assessed (40 logcount curves generated): salt replacement by addition
      of organic acids, sorbic acid replacement by addition of acetic and lactic acid,
      and sorbic acid replacement by addition of lactic/acetic acid and salt. For the
      three rules, the growth rates were equivalent in the whole experimental domain
      (gamma from 0.1 to 0.5). The lag times were also equivalent in the case of mild
      inhibitory conditions (gamma >= 0.2), while they were longer in the presence of
      salt than acids under stress conditions (gamma < 0.2). This methodology allows an
      assessment of the equivalence of inhibitory effects without intensive data
      generation; it could be applied to develop milder formulations which guarantee
      microbial safety and stability.

PMID- 22156427
TI  - Characterization of blaCMY-2 plasmids in Salmonella and Escherichia coli isolates
      from food animals in Canada.
AB  - One hundred thirty-four bla(CMY-2) plasmids from Salmonella and Escherichia coli
      strains from animals and food in Canada were characterized. Five plasmid groups
      were identified based on replicon type and restriction profiles. Three groups
      contained E. coli plasmids only. IncA/C plasmids included most multiresistant
      plasmids and all those of bovine origin.

PMID- 22156428
TI  - Impact of feed efficiency and diet on adaptive variations in the bacterial
      community in the rumen fluid of cattle.
AB  - Limited knowledge of the structure and activities of the ruminal bacterial
      community prevents the understanding of the effect of population dynamics on
      functional bacterial groups and on host productivity. This study aimed to
      identify particular bacteria associated with host feed efficiency in steers with
      differing diets and residual feed intake (RFI) using culture-independent methods:
      PCR-denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR
      analysis. PCR-DGGE profiles were generated from the ruminal fluid of 55 steers
      fed a low-energy-density diet and then switched to a high-energy-density diet.
      Bacterial profile comparisons by multivariate statistical analysis showed a trend
      only for RFI-related clusters on the high-energy diet. When steers (n = 19)
      belonging to the same RFI group under both diets were used to identify specific
      bacterial phylotypes related to feed efficiency traits, correlations were
      detected between dry matter intake, average daily gain, and copy numbers of the
      16S rRNA gene of Succinivibrio sp. in low-RFI (efficient) steers, whereas
      correlations between Robinsoniella sp. and RFI (P < 0.05) were observed for high
      RFI (inefficient) animals. Eubacterium sp. differed significantly (P < 0.05)
      between RFI groups that were only on the high-energy diet. Our work provides a
      comprehensive framework to understand how particular bacterial phylotypes
      contribute to differences in feed efficiency and ultimately influence host
      productivity, which may either depend on or be independent from diet factors.

PMID- 22156429
TI  - Interaction forces drive the environmental transmission of pathogenic protozoa.
AB  - The protozoan parasites Giardia duodenalis, Cryptosporidium spp., and Toxoplasma
      gondii are pathogens that are resistant to a number of environmental factors and
      pose significant risks to public health worldwide. Their environmental
      transmission is closely governed by the physicochemical properties of their cysts
      (Giardia) and oocysts (Cryptosporidium and Toxoplasma), allowing their transport,
      retention, and survival for months in water, soil, vegetables, and mollusks,
      which are the main reservoirs for human infection. Importantly, the cyst/oocyst
      wall plays a key role in that regard by exhibiting a complex polymeric coverage
      that determines the charge and hydrophobic characteristics of parasites'
      surfaces. Interaction forces between parasites and other environmental particles
      may be, in a first approximation, evaluated following the Derjaguin-Landau-Verwey
      Overbeek (DLVO) theory of colloidal stability. However, due to the molecular
      topography and nano- to microstructure of the cyst/oocyst surface, non-DVLO
      hydrophobic forces together with additional steric attractive and/or repulsive
      forces may play a pivotal role in controlling the parasite behavior when the
      organism is subjected to various external conditions. Here, we review several
      parameters that enhance or hinder the adhesion of parasites to other particles
      and surfaces and address the role of fast-emerging techniques for mapping the
      cyst/oocyst surface, e.g., by measuring its topology and the generated
      interaction forces at the nano- to microscale. We discuss why characterizing
      these interactions could be a crucial step for managing the environmental
      matrices at risk of microbial pollution.

PMID- 22156430
TI  - Metatranscriptomic analysis of microbes in an Oceanfront deep-subsurface hot
      spring reveals novel small RNAs and type-specific tRNA degradation.
AB  - Studies of small noncoding RNAs (sRNAs) have been conducted predominantly using
      culturable organisms, and the acquisition of further information about sRNAs from
      global environments containing uncultured organisms now is very important. In
      this study, hot spring water (57 degrees C, pH 8.1) was collected directly from
      the underground environment at depths of 250 to 1,000 m in Yunohama, Japan, and
      small RNA sequences obtained from the environment were analyzed. A phylogenetic
      analysis of both archaeal and bacterial 16S rRNA gene sequences was conducted,
      and the results suggested the presence of unique species in the environment,
      corresponding to the Archaeal Richmond Mine Acidophilic Nanoorganisms (ARMAN)
      group and three new Betaproteobacteria. A metatranscriptomic analysis identified
      64,194 (20,057 nonredundant) cDNA sequences. Of these cDNAs, 90% were either
      tRNAs, tRNA fragments, rRNAs, or rRNA fragments, whereas 2,181 reads (10%) were
      classified as previously uncharacterized putative candidate sRNAs. Among these,
      15 were particularly abundant, 14 of which showed no sequence similarity to any
      known noncoding RNA, and at least six of which form very stable RNA secondary
      structures. The analysis of a large number of tRNA fragments suggested that
      unique relationships exist between the anticodons of the tRNAs and the sites of
      tRNA degradation. Previous bacterial tRNA degradation studies have been limited
      to specific organisms, such as Escherichia coli and Streptomyces coelicolor, and
      the current results suggest that specific tRNA decay occurs more frequently than
      previously expected.

PMID- 22156431
TI  - Isolation and characterization of environmental bacteria capable of extracellular
      biosorption of mercury.
AB  - Accumulation of toxic metals in the environment represents a public health and
      wildlife concern. Bacteria resistant to toxic metals constitute an attractive
      biomass for the development of systems to decontaminate soils, sediments, or
      waters. In particular, biosorption of metals within the bacterial cell wall or
      secreted extracellular polymeric substances (EPS) is an emerging process for the
      bioremediation of contaminated water. Here the isolation of bacteria from soil,
      effluents, and river sediments contaminated with toxic metals permitted the
      selection of seven bacterial isolates tolerant to mercury and associated with a
      mucoid phenotype indicative of the production of EPS. Inductively coupled plasma
      optical emission spectroscopy and transmission electron microscopy in conjunction
      with X-ray energy dispersive spectrometry revealed that bacteria incubated in the
      presence of HgCl2 sequestered mercury extracellularly as spherical or amorphous
      deposits. Killed bacterial biomass incubated in the presence of HgCl2 also
      generated spherical extracellular mercury deposits, with a sequestration capacity
      (40 to 120 mg mercury per g [dry weight] of biomass) superior to that of live
      bacteria (1 to 2 mg mercury per g [dry weight] of biomass). The seven strains
      were shown to produce EPS, which were characterized by Fourier transform-infrared
      (FT-IR) spectroscopy and chemical analysis of neutral-carbohydrate, uronic acid,
      and protein contents. The results highlight the high potential of Hg-tolerant
      bacteria for applications in the bioremediation of mercury through biosorption
      onto the biomass surface or secreted EPS.

PMID- 22156432
TI  - CTX-M-15 extended-spectrum beta-lactamase in a shiga toxin-producing Escherichia
      coli isolate of serotype O111:H8.
AB  - We report the discovery of a CTX-M-15-producing Escherichia coli (STEC) of
      serogroup O111:H8, a major serotype responsible for human enterohemorrhagic
      Escherichia coli (EHEC) infections. In line with the recent CTX-M-15/O104:H4 E.
      coli outbreak, these data may reflect an accelerating spread of resistance to
      expanded-spectrum cephalosporins within the E. coli population, including STEC
      isolates.

PMID- 22156433
TI  - Novel antiviral characteristics of nanosized copper(I) iodide particles showing
      inactivation activity against 2009 pandemic H1N1 influenza virus.
AB  - We investigated the antiviral activity of nanosized copper(I) iodide (CuI)
      particles having an average size of 160 nm. CuI particles showed aqueous
      stability and generated hydroxyl radicals, which were probably derived from
      monovalent copper (Cu(+)). We confirmed that CuI particles showed antiviral
      activity against an influenza A virus of swine origin (pandemic [H1N1] 2009) by
      plaque titration assay. The virus titer decreased in a dose-dependent manner upon
      incubation with CuI particles, with the 50% effective concentration being
      approximately 17 MUg/ml after exposure for 60 min. SDS-PAGE analysis confirmed
      the inactivation of the virus due to the degradation of viral proteins such as
      hemagglutinin and neuraminidase by CuI. Electron spin resonance (ESR)
      spectroscopy revealed that CuI generates hydroxyl radicals in aqueous solution,
      and radical production was found to be blocked by the radical scavenger N
      acetylcysteine. Taken together, these findings indicate that CuI particles exert
      antiviral activity by generating hydroxyl radicals. Thus, CuI may be a useful
      material for protecting against viral attacks and may be suitable for
      applications such as filters, face masks, protective clothing, and kitchen
      cloths.

PMID- 22156434
TI  - Diversity of five anaerobic toluene-degrading microbial communities investigated
      using stable isotope probing.
AB  - Time-series DNA-stable isotope probing (SIP) was used to identify the microbes
      assimilating carbon from [(13)C]toluene under nitrate- or sulfate-amended
      conditions in a range of inoculum sources, including uncontaminated and
      contaminated soil and wastewater treatment samples. In all, five different
      phylotypes were found to be responsible for toluene degradation, and these
      included previously identified toluene degraders as well as novel toluene
      degrading microorganisms. In microcosms constructed from granular sludge and
      amended with nitrate, the putative toluene degraders were classified in the genus
      Thauera, whereas in nitrate-amended microcosms constructed from a different
      source (agricultural soil), microorganisms in the family Comamonadaceae (genus
      unclassified) were the key putative degraders. In one set of sulfate-amended
      microcosms (agricultural soil), the putative toluene degraders were identified as
      belonging to the class Clostridia (genus Desulfosporosinus), while in other
      sulfate-amended microcosms, the putative degraders were in the class
      Deltaproteobacteria, within the family Syntrophobacteraceae (digester sludge) or
      Desulfobulbaceae (contaminated soil) (genus unclassified for both). Partial
      benzylsuccinate synthase gene (bssA, the functional gene for anaerobic toluene
      degradation) sequences were obtained for some samples, and quantitative PCR
      targeting this gene, along with SIP, was further used to confirm anaerobic
      toluene degradation by the identified species. The study illustrates the
      diversity of toluene degraders across different environments and highlights the
      utility of ribosomal and functional gene-based SIP for linking function with
      identity in microbial communities.

PMID- 22156435
TI  - Functional characterization of Crp/Fnr-type global transcriptional regulators in
      Desulfovibrio vulgaris Hildenborough.
AB  - Crp/Fnr-type global transcriptional regulators regulate various metabolic
      pathways in bacteria and typically function in response to environmental changes.
      However, little is known about the function of four annotated Crp/Fnr homologs
      (DVU0379, DVU2097, DVU2547, and DVU3111) in Desulfovibrio vulgaris Hildenborough.
      A systematic study using bioinformatic, transcriptomic, genetic, and
      physiological approaches was conducted to characterize their roles in stress
      responses. Similar growth phenotypes were observed for the crp/fnr deletion
      mutants under multiple stress conditions. Nevertheless, the idea of distinct
      functions of Crp/Fnr-type regulators in stress responses was supported by
      phylogeny, gene transcription changes, fitness changes, and physiological
      differences. The four D. vulgaris Crp/Fnr homologs are localized in three
      subfamilies (HcpR, CooA, and cc). The crp/fnr knockout mutants were well
      separated by transcriptional profiling using detrended correspondence analysis
      (DCA), and more genes significantly changed in expression in a DeltaDVU3111
      mutant (JW9013) than in the other three paralogs. In fitness studies, strain
      JW9013 showed the lowest fitness under standard growth conditions (i.e., sulfate
      reduction) and the highest fitness under NaCl or chromate stress conditions;
      better fitness was observed for a DeltaDVU2547 mutant (JW9011) under nitrite
      stress conditions and a DeltaDVU2097 mutant (JW9009) under air stress conditions.
      A higher Cr(VI) reduction rate was observed for strain JW9013 in experiments with
      washed cells. These results suggested that the four Crp/Fnr-type global
      regulators play distinct roles in stress responses of D. vulgaris. DVU3111 is
      implicated in responses to NaCl and chromate stresses, DVU2547 in nitrite stress
      responses, and DVU2097 in air stress responses.

PMID- 22156436
TI  - Selected lactic acid bacteria synthesize antioxidant peptides during sourdough
      fermentation of cereal flours.
AB  - A pool of selected lactic acid bacteria was used for the sourdough fermentation
      of various cereal flours with the aim of synthesizing antioxidant peptides. The
      radical-scavenging activity of water/salt-soluble extracts (WSE) from sourdoughs
      was significantly (P < 0.05) higher than that of chemically acidified doughs. The
      highest activity was found for whole wheat, spelt, rye, and kamut sourdoughs.
      Almost the same results were found for the inhibition of linoleic acid
      autoxidation. WSE were subjected to reverse-phase fast protein liquid
      chromatography. Thirty-seven fractions were collected and assayed in vitro. The
      most active fractions were resistant to further hydrolysis by digestive enzymes.
      Twenty-five peptides of 8 to 57 amino acid residues were identified by nano
      liquid chromatography-electrospray ionization-tandem mass spectrometry. Almost
      all of the sequences shared compositional features which are typical of
      antioxidant peptides. All of the purified fractions showed ex vivo antioxidant
      activity on mouse fibroblasts artificially subjected to oxidative stress. This
      study demonstrates the capacity of sourdough lactic acid bacteria to release
      peptides with antioxidant activity through the proteolysis of native cereal
      proteins.

PMID- 22156437
TI  - Discovery of functional gene variants associated with human longevity:
      opportunities and challenges.
AB  - Age is a major risk factor for many human diseases. Extremely long-lived
      individuals, such as centenarians, have managed to ward off age-related diseases
      and serve as human models to search for the genetic factors that influence
      longevity. The discovery of evolutionarily conserved pathways with major impact
      on life span in animal models has provided tantalizing opportunities to test the
      relevance of these pathways for human longevity. Here we specifically focus on
      the insulin/insulin-like growth factor-1 signaling as a prime candidate pathway.
      Coupled with the rapid advances in ultra high-throughput sequencing technologies,
      it is now feasible to comprehensively analyze all possible sequence variants in
      candidate genes segregating with a longevity phenotype and to investigate the
      functional consequences of the associated variants. A better understanding of the
      functional genes that affect healthy longevity in humans may lead to a rational
      basis for intervention strategies that can delay or prevent age-related diseases.

PMID- 22156438
TI  - Age- and sex-associated plasma proteomic changes in growth hormone receptor gene
      disrupted mice.
AB  - Growth hormone receptor gene-disrupted (GHR-/-) mice are dwarf, insulin
      sensitive, and long lived despite being obese. In order to identify
      characteristics associated with their increased longevity, we studied age-related
      plasma proteomic changes in these mice. Male and female GHR-/- mice and their
      littermate controls were followed longitudinally at 8, 16, and 24 months of ages
      for plasma proteomic analysis. Relative to control littermates, GHR-/- mice had
      increased levels of apolipoprotein A-4 and retinol-binding protein-4 and
      decreased levels of apolipoprotein E, haptoglobin, and mannose-binding protein-C.
      Female GHR-/- mice showed decreased inflammatory cytokines including interleukin
      1beta and monocyte chemotactic protein-1. Additionally, sex differences were
      found in specific isoforms of apolipoprotein E, RBP-4, haptoglobin, albumin, and
      hemoglobin subunit beta. In conclusion, we find plasma proteomic changes in GHR-/
      mice that favor a longer life span as well as sex differences indicative of an
      improved health span in female mice.

PMID- 22156439
TI  - Serum 25-hydroxyvitamin D and pulmonary function in older disabled community
      dwelling women.
AB  - BACKGROUND: Recent studies have expanded the functions of vitamin D to a possible
      role in pulmonary function. Our objective was to examine the relationship between
      serum 25-hydroxyvitamin D (25[OH]D), serum parathyroid hormone, and pulmonary
      function in older women. METHODS: We examined the relationship of serum 25(OH)D
      and parathyroid hormone with pulmonary function (forced expiratory volume in one
      second [FEV(1)], forced vital capacity [FVC], and FEV(1)/FVC ratio) in a cross
      sectional study of 646 moderately to severely disabled women, 65 years or more,
      living in the community in Baltimore, Maryland, who participated in the Women's
      Health and Aging Study I. RESULTS: Overall, median (25th, 75th percentile) serum
      25-hydroxyvitamin D concentrations were 19.9 (14.7, 26.7) ng/mL. Serum 25(OH)D
      was positively associated with FEV(1) (p = .03), FVC (p = .18), and FEV(1)/FVC (p
      = .04) in multivariable linear regression models adjusting for age, race,
      education, smoking, height, physical activity, cognition, interleukin-6, chronic
      diseases, and other potential confounders. In the same models, serum parathyroid
      hormone was not significantly associated with FEV(1), FVC, or FEV(1)/FVC.
      CONCLUSIONS: These findings support the idea that vitamin D deficiency is
      independently associated with poor pulmonary function in older disabled women.

PMID- 22156440
TI  - Prognostic stratification of elderly patients in the emergency department: a
      comparison between the "Identification of Seniors at Risk" and the "Silver Code".
AB  - BACKGROUND: The increasing number of elderly patients accessing emergency
      departments (EDs) requires use of validated assessment tools. We compared the
      Identification of Seniors at Risk (ISAR), using direct patient evaluation, with
      the Silver Code (SC), based on administrative data. METHODS: Subjects aged 75+
      years accessing a geriatric ED over an 8-month period were enrolled. Outcomes
      were need for hospital admission and mortality at the index ED access, ED return
      visit, hospitalization, and death at 6 months. RESULTS: Of 1,632 participants
      (mean age 84 +/- 5.5 years), 75% were ISAR positive, and the sample was
      homogeneously distributed across the four SC risk categories (cutoffs of 0-3, 4
      6, 7-10, and 11+). The two scores were mildly correlated (r = .350, p < .001) and
      had a similar area under the receiver-operating characteristic curve in
      predicting hospital admission (ISAR: 0.65, SC: 0.63) and mortality (ISAR: 0.72,
      SC: 0.70). ISAR-positive subjects were at greater risk of hospitalization and
      death (odds ratio 2.68 and 5.23, respectively, p < .001); the risk increased
      across SC classes (p < .001). In the 6-month follow-up of discharged patients,
      the tools predicted similarly ED return visit, hospital admission, and mortality.
      The SC predicted these outcomes even in participants not hospitalized at the
      index ED access. CONCLUSIONS: Prognostic stratification of elderly ED patients
      with the SC is comparable with that obtained with direct patient evaluation. The
      SC, previously validated in hospitalized patients, predicts ED readmissions and
      future hospitalizations even in patients discharged directly from the ED.

PMID- 22156441
TI  - Pituitary adenoma apoplexy presenting with bilateral third nerve palsy and
      bilateral proptosis: a case report.
AB  - OBJECTIVE: To report a case of pituitary adenoma apoplexy presenting with
      bilateral proptosis and bilateral third nerve palsy that developed after
      cardiovascular surgery. CLINICAL PRESENTATION AND INTERVENTION: A 45-year-old man
      developed bilateral proptosis and bilateral third nerve palsy after a coronary
      artery bypass grafting operation. A pituitary macroadenoma with extension into
      the sphenoid sinus and cavernous sinus with bilateral involvement was resected on
      computed tomography scan by microscopic transsphenoidal procedure. Third nerve
      palsy improved partially on the first postoperative day and completely improved
      in the fourth month after the operation. CONCLUSION: This is a rare case of
      pituitary adenoma apoplexy that presented with bilateral third cranial nerve
      palsy.

PMID- 22156443
TI  - Perspectives for onkologie.

PMID- 22156444
TI  - Cancer stem cells in ulcerative colitis.

PMID- 22156442
TI  - Estrogen receptor-Beta variants are associated with increased risk of Alzheimer's
      disease in women with down syndrome.
AB  - BACKGROUND/AIMS: Genetic variants that affect estrogen activity may influence the
      risk of Alzheimer's disease (AD). We examined the relation of polymorphisms in
      the gene for the estrogen receptor-beta (ESR2) to the risk of AD in women with
      Down syndrome. METHODS: Two hundred and forty-nine women with Down syndrome, 31
      70 years of age and nondemented at baseline, were followed at 14- to 18-month
      intervals for 4 years. Women were genotyped for 13 single-nucleotide
      polymorphisms (SNPs) in the ESR2 gene, and their association with AD incidence
      was examined. RESULTS: Among postmenopausal women, we found a 2-fold increase in
      the risk of AD for women carrying 1 or 2 copies of the minor allele at 3 SNPs in
      introns seven (rs17766755) and six (rs4365213 and rs12435857) and 1 SNP in intron
      eight (rs4986938) of ESR2. CONCLUSION: These findings support a role for estrogen
      and its major brain receptors in modulating susceptibility to AD in women.

PMID- 22156445
TI  - Surgical resection of isolated adrenal metastases in patients with non-small cell
      lung cancer: a single-institution experience and review of the literature.
AB  - BACKGROUND: In non-small cell lung cancer (NSCLC), the benefits of resection of
      solitary adrenal metastases for survival and the identification of patients most
      likely to benefit from adrenalectomy are unknown. PATIENTS AND METHODS: We
      retrospectively reviewed clinico-pathological factors and outcomes in 4 NSCLC
      patients treated with adrenalectomy at our centre. We reviewed the published
      literature with a focus on long-term survivors in order to formulate treatment
      recommendations. RESULTS: Local pathological staging showed stages IA-IIA. All
      had a performance status (PS) of 0. The median age was 56 years (range: 53-58
      years). Adrenal metastases were detected by positron emission tomography-computed
      tomography (PET-CT) in 3 patients. Median time from lobectomy to occurrence of
      metachronous adrenal metastases was 12.3 months (11-14 months). The perioperative
      mortality was zero. All patients recurred systemically after adrenalectomy within
      2-49 months. 3 patients died due to systemic progression 6-15 months after
      adrenalectomy. 1 patient is alive with pulmonary relapse 49 months after
      adrenalectomy. CONCLUSIONS: Resection of solitary adrenal metastases in selected
      good-PS NSCLC patients with minimal local nodal involvement from the primary
      tumour is associated with low morbidity and may offer a chance for long-term
      disease-free survival in a small subset of patients. Careful pre-operative
      staging including PET-CT is warranted.

PMID- 22156447
TI  - Signet ring cell carcinoma of the stomach is significantly associated with poor
      prognosis and diffuse gastric cancer (Lauren's): single-center experience of 160
      cases.
AB  - AIM: The aim of this study was to evaluate survival rates and treatment response
      in stage I-IV gastric cancer in relation to tumor stage (TNM), histology,
      Lauren's classification and tumor localization. PATIENTS AND METHODS: Clinical
      and histopathological data of 160 patients with stage I-IV gastric cancer were
      analyzed in this retrospective, single-center study. RESULTS: Most patients
      (73.1%) showed an advanced or metastatic tumor stage (III/IV). The median 3-year
      overall survival (OS) was 20 +/- 16.8 months and correlated significantly with
      tumor stage (I: OS 30.6 +/- 15 months vs. IV: 10.4 +/- 9.3 months; p < 0.0001).
      Stage III/IV tumors were significantly more often poorly differentiated (G3; p =
      0.011) and located in the corpus region. Signet ring cell (SRC) cancers were
      found in a larger proportion of these tumors when compared with locally limited
      gastric cancers (43.1% vs. 16.3%; p = 0.002). SRC tumors occurred predominantly
      in women and younger patients and histology was significantly more often of the
      diffuse subtype according to Lauren (7.5% vs. 63.2%; p < 0.0001) and poorly
      differentiated (G3 in 95% vs. 73%; p = 0.001). CONCLUSIONS: SRC gastric cancer
      correlates with poor histopathological criteria and poor prognosis when compared
      with other histological subtypes. These observations underline the need for more
      effective treatment in addition to standard approaches.

PMID- 22156446
TI  - Plasma miR-221 as a predictive biomarker for chemoresistance in breast cancer
      patients who previously received neoadjuvant chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly being used in breast
      cancer treatment. Research has revealed an elevated expression of miR-221 in
      adriamycinresistant MCF-7/ADR cells. This study aimed to explore the potential
      role of miR-221 as a biomarker for chemosensitivity in breast cancer patients who
      previously received NAC. PATIENTS AND METHODS: The expression levels of
      circulating miR-221 in the plasma of 93 breast cancer patients who previously
      received NAC and in 32 healthy individuals were assessed. The correlations
      between miR-221 and clinicopathological features and chemosensitivity were also
      analysed. RESULTS: The expression level of miR-221 was significantly associated
      with hormone receptor (HR) status (p = 0.008). Patients with higher plasma miR
      221 levels tended to be HR-negative. Patients with different miR-221 levels had
      significant differences in the overall response rate (p = 0.044) but not in the
      pathologic complete response rate (p = 0.477). CONCLUSION: Our results indicate
      that plasma miR-221 may be a predictive biomarker for sensitivity to NAC in
      breast cancer patients.

PMID- 22156448
TI  - Does colorectal cancer in ulcerative colitis patients constitute a risk for
      chemotherapy refractoriness?:a systemic approach by detailed analysis via the
      electronic tumor base documentation system.
AB  - BACKGROUND: Ulcerative colitis (UC) patients may develop colorectal cancer (CRC),
      especially with pancolitis and longer UC duration. The question whether CRC with
      underlying UC has a dismal prognosis remains unsettled. PATIENTS AND METHODS: We
      performed an electronic tumor base documentation (eTBD) search of CRC and UC
      patients at our department to address whether (1) CRC prognosis is impaired and
      (2) defined risks can be determined. RESULTS: With the inclusion of an index
      patient with UC and unresponsive CRC, 20 additional patients were identified via
      eTBD. Chemotherapy response was less substantial, with complete response or
      stable disease in 3 patients each, but rapidly progressing or refractory disease
      in 15/21 patients. 12 out of the 21 patients died. Our hazard ratio analysis
      revealed International Union against Cancer (UICC) stage IV and III disease,
      grade 3 tumors, longer latency from UC to CRC and age >60 years as potential
      risks. Median progression-free survival and overall survival were 48 and 82
      months, respectively. Time from tumor dissemination to death was 10 months.
      CONCLUSIONS: The prognosis of CRC in UC patients is not necessarily impaired,
      albeit chemotherapy response with disseminated disease may be unfavorable. Our
      data should be enlarged by subsequent analyses to better elucidate whether
      response in UC and CRC is more challenging and defined risks can be confirmed.

PMID- 22156449
TI  - 5FU continuous infusion in heavily pretreated advanced breast cancer patients.
AB  - BACKGROUND: Despite advances in the first- and secondline treatment of advanced
      breast cancer, optimal therapy thereafter remains controversial. Treatment of
      heavily pretreated patients is not standardized, often of low efficacy, and
      limited by comorbidity. In these patients, an effective treatment with low
      toxicity is needed. PATIENTS AND METHODS: We retrospectively analyzed all
      metastatic breast cancer patients treated with 5-fluorouracil as continuous
      infusion (CI-5FU) with daily doses of 150-300 mg/m(2). RESULTS: 43 patients were
      treated with CI-5FU until disease progression. The median number of metastatic
      sites was 3. Most patients were heavily pretreated with a median of 3 palliative
      chemotherapies (range 1-11). 42 patients were evaluable for objective response;
      among them 5 (12%) showed a partial response (PR) and 6 (15%) showed stable
      disease (SD) lasting at least 6 months, leading to a clinical benefit (CB) rate
      (complete response + PR + SD >= 6 months) of 27%. The median time to progression
      of patients with CB was 10 months (range 3-22). Overall survival of all patients
      from the start of CI-5FU was 8 months (range 1-75) and from the time of first
      metastases 42 months (range 9-281). Toxicity was low even in patients with
      hepatic insufficiency. CONCLUSION: CI-5FU showed a positive efficacy/toxicity
      ratio. Taking into account the high number of previous treatments, it results in
      a remarkable CB rate of 27%.

PMID- 22156450
TI  - Bisphosphonate therapy is effective in the treatment of sacral giant cell tumor.
AB  - BACKGROUND: Sacral giant cell tumors are particularly challenging to treat as
      they are often quite extensive and surround the sacral nerve roots, making
      surgical extirpation very difficult without high morbidity and frequent local
      recurrence. CASE REPORT: We report on a 33-year old male patient with sacral
      giant cell tumor treated with intravenous bisphosphonate therapy after early
      failure of embolization procedures. At 3 years follow-up, the patient had no
      pain, no neurological deficits, and no local recurrence. CONCLUSION: To our
      knowledge, this is one of the first reported cases of bisphosphonate therapy
      after failed embolization for control of a difficult giant cell tumor.

PMID- 22156451
TI  - Well-differentiated hand liposarcoma with bone metastases treated successfully
      with zoledronic Acid.
AB  - BACKGROUND: Well-differentiated liposarcomas of the upper extremities, such as
      the hand or forearm, are extremely rare and are commonly misdiagnosed and
      considered benign. They are frequently reported as having low metastatic
      potential. CASE REPORT: We report the case of a 58-year-old man with well
      differentiated hand liposarcoma and diffuse bone metastases. The patient
      initially presented with a tumor of the thenar eminence and was treated with
      marginal surgical excision and external beam irradiation. 4 months after this
      treatment, soft tissue local recurrence and skeletal metastases were detected.
      Zoledronic acid treatment (4 mg per month) was initiated, and both the tumor and
      the metastases regressed. The patient remains cancer-free 3.5 years after
      diagnosis of the metastatic disease. CONCLUSION: Significant metastatic disease
      can develop in patients with well-differentiated liposarcomas. The beneficial
      effect of zoledronic acid observed in this case may be related to its anticancer
      properties, as described in phase III trials in various tumor types.

PMID- 22156452
TI  - Reduced-intensity conditioning in allogeneic stem cell transplantation for
      hematological malignancies: a historical perspective.
AB  - Allogeneic hematopoietic stem cell transplantation represents a curative
      treatment approach for a large range of hematologic malignancies. Traditionally,
      high-dose radiochemotherapy as preparative regimen has been thought to be
      necessary for successful allogeneic stem cell transplantation. However, high-dose
      conditioning often results in considerable medullary and extramedullary toxicity,
      contributing to high rates of treatment-related mortality. This limits the use of
      this procedure to patients below 60 years of age without significant
      comorbidities. Since the peak incidence of most hematological malignancies is
      beyond the 5th decade of life, the majority of patients are not eligible for high
      dose treatment. During the last 15 years, several dose-reduced or even non
      myeloablative conditioning regimens have been developed, offering a curative
      treatment option for these patients. This review summarizes the history of
      reduced-intensity conditioning (RIC) transplantations, depicts the differences
      among regimens, highlights significant patient factors, and describes the impact
      on selected hematological malignancies.

PMID- 22156453
TI  - Novel therapeutic approach for neurodegenerative pathologies: multitarget iron
      chelating drugs regulating hypoxia-inducible factor 1 signal transduction
      pathway.
AB  - Our novel multimodal brain-permeable iron-chelating compounds M30 and HLA20 were
      demonstrated to possess neuroprotective/neurorescue activities in vitro and in
      vivo against several insults applicable to various neurodegenerative diseases,
      such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral
      sclerosis. Neuroprotection by iron chelators has been widely recognized with
      respect to their ability to prevent reactive oxygen species generation in the
      Fenton reaction by sequestering redox-active iron. An additional neuroprotective
      mechanism of iron-chelating compounds is associated with their ability to
      regulate the transcriptional activator hypoxia-inducible factor 1 (HIF-1). HIF-1
      is a 'master switch' being an important physiological response mechanism, likely
      enhancing neuroprotective compensatory pathways involved in many physiological
      processes within the brain. This mini-review will discuss the multifunctional
      mechanisms of action of the drugs, M30 and HLA20 in preclinical models of
      neurodegeneration with a specific emphasis on their ability to activate the HIF-1
      signal transduction pathway.

PMID- 22156454
TI  - Food prehension and manipulation in Microcebus murinus (Prosimii,
      Cheirogaleidae).
AB  - Among primates, apes and monkeys are known to use their hands and to exhibit
      independent control of their fingers. In comparison, Prosimii are thought to have
      less digital individualization and to use their mouth more commonly for
      prehension. Unfortunately, prehension and manipulation studies in Prosimii have
      been conducted in conditions constraining the subject to grasp with the hand.
      Moreover, the effect of food size remains unexplored, even though it could affect
      the use of the hands versus the mouth. Thus, whether prosimians use the hand or
      the mouth to grasp and manipulate food items of different sizes in unconstrained
      conditions remains unclear. To address this question, we characterized the eating
      and manipulation patterns of Microcebus murinus in unconstrained conditions,
      using three food sizes. The results showed that M. murinus showed (i) an eating
      pattern similar to that of rodents, with smaller food items being grasped with
      the mouth, (ii) a greater tendency to use the hands for prehension of larger
      foods, and (iii) plasticity during food manipulation similar to that which has
      been observed in rodents. These results are discussed in the framework of
      grasping in mammals and are used to discuss the origins of prehension in
      primates.

PMID- 22156455
TI  - Thyroid FNA: challenges and opportunities.

PMID- 22156456
TI  - Variability in the atypia of undetermined significance/follicular lesion of
      undetermined significance diagnosis in the Bethesda System for Reporting Thyroid
      Cytopathology: sources and recommendations.
AB  - OBJECTIVE: Of the 6 categories in the Bethesda System for Reporting Thyroid
      Cytopathology (BSRTC), the atypia of undetermined significance/follicular lesion
      of undetermined significance (AUS/FLUS) category has received the most attention.
      The objectives of this study were to review the use of the AUS/FLUS category in
      recent studies, to search for likely sources of the variability in its use, and
      to address possible methods for improvement. STUDY DESIGN: A PubMed search was
      performed to retrieve peer-reviewed articles that have comprehensively detailed
      the incidence and outcome of AUS/FLUS and other BSRTC categories. Related thyroid
      cytology articles on the BSRTC were also included. RESULTS: Recent series that
      reported experiences with the BSRTC categories showed that the AUS/FLUS category
      exhibited a marked variability in incidence (0.7-18%) and malignant outcome (6
      48%) in resection specimens. Review of the literature revealed institutional
      differences in technical aspects, interpretation and application of criteria,
      analysis of outcome data, and clinicopathologic interactions. CONCLUSIONS: A
      heightened awareness of technical issues, diagnostic borders of AUS/FLUS, and
      clinical management may aid in diagnostic refinement and help avoid overuse of
      this category.

PMID- 22156457
TI  - The UK Royal College of Pathologists thyroid fine-needle aspiration diagnostic
      classification is a robust tool for the clinical management of abnormal thyroid
      nodules.
AB  - OBJECTIVE: To compare the outcomes and evaluate the relative risk of thyroid
      cancer by using the UK thyroid fine-needle aspiration (FNA) cytological
      diagnostic categories, with the main objective being the clarity of patient
      management. STUDY DESIGN: Results of thyroid FNA reported as Thy3a, Thy3f, Thy4,
      and Thy5 were correlated with histological outcomes. The specificity and positive
      predictive value (PPV; risk of malignancy) for each reporting category was
      assessed. RESULTS: Of a total of 873 thyroid FNAs, 237 (27%) were reported as
      'abnormal': 40 (4.6%) as Thy3a, 119 (13.6%) as Thy3f, 20 (2.2%) as Thy4, and 58
      (6.6%) as Thy 5. The final outcomes were available in 136 (57%) cases which
      underwent surgical resection (25, 60, 55, and 74% of Thy3a, Thy3f, Thy4, and
      Thy5, respectively). The known outcomes of the Thy3a category were too low to be
      statistically significant. The specificity and PPV of the Thy3f, Thy4, and Thy5
      (equivalent to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)
      IV, V, and VI) categories were 50, 50, and 100% and 28, 64, and 100%,
      respectively. The PPV of Thy3f for diagnosis of 'neoplasms' (benign and
      malignant) was 63%. CONCLUSION: The current thyroid FNA classification system
      used in the UK, which is comparable to TBSRTC, offers a sound basis for clear
      communication on which the management of patients with abnormal thyroid FNA
      findings can be based. Categories Thy3f, Thy4, and Thy5 carry a progressively
      rising risk of malignancy, justifying their continuing use. Diagnostic category
      Thy5 'malignant' is robust and can be used as a sure indication of a definitive
      surgical management.

PMID- 22156458
TI  - The Bethesda terminology for reporting thyroid cytopathology: from theory to
      practice in Europe.
AB  - OBJECTIVES: A 2007 conference held at the National Cancer Institute, Bethesda,
      Md., USA, proposed a new terminology for classifying the results of thyroid fine
      needle aspiration (FNA) - The Bethesda System for Reporting Thyroid Cytology
      (TBSRTC). The need to standardize thyroid FNA terminology was emphasized during
      the 35th European Congress of Cytology in 2009. An interobserver review study to
      assess the new terminology for analyzing the results of thyroid FNA was organized
      by the scientific committee of the European Federation of Cytology Societies.
      STUDY DESIGN: Four experts in thyroid FNA examined and classified 116 FNAs
      according to the 6 levels of TBSRTC which are: nondiagnostic (ND); benign; atypia
      of undetermined significance/follicular lesion of undetermined significance
      (AUS/FLUS); follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN),
      with those of Hurthle cell type reported as follicular neoplasm, Hurthle cell
      type/suspicious for a follicular neoplasm, Hurthle cell type (FNHCT/SFNHCT);
      suspicious (SUS), and malignant. RESULTS: The total consensus was 62.1%; the
      cytopathologists disagreed on 44 cases, including 8 cases of AUS/FLUS and 18 of
      FN/SFN; 59% of the cases had no consensus. They agreed on 73 and 80% of the cases
      classified as benign and malignant, respectively, and on 58.3% of the SUS cases.
      The percentage of no consensus for each expert was between 32 and 39%.
      CONCLUSIONS: Disagreement regarding the use of TBSRTC terminology for classifying
      the results of thyroid FNA mainly occurred in the most-often criticized
      categories of AUS/FLUS and FN/SFN.

PMID- 22156459
TI  - The frequency of 'atypia of undetermined significance' interpretations for
      thyroid fine-needle aspirations is negatively correlated with histologically
      proven malignant outcomes.
AB  - OBJECTIVE: Cytopathologists' usage patterns for 'atypia of undetermined
      significance' (AUS) in thyroid fine-needle aspiration (FNA) are not well
      understood. AUS rates over a 5-year period were analyzed to quantify variability
      and identify correlations with experience and histologic outcomes. STUDY DESIGN:
      A retrospective review of thyroid FNAs from a tertiary-care hospital from 2005 to
      2009 was performed. Results were compiled for individual cytopathologists,
      stratified by year, and correlated with histologic outcomes. RESULTS: Thyroid
      FNAs (5,327) were evaluated by 7 cytopathologists, with an overall AUS rate of
      11.2%. The annual AUS rate remained relatively constant over this time period,
      though notable inter- and intrapathologist variability was seen. The AUS rate was
      significantly lower for those with cytopathology boards (10.3%) compared to those
      without (14.0%). There was no correlation between the AUS rate and
      cytopathologist experience or thyroid FNA volume. The AUS rate and malignant
      outcome were inversely related: the higher an individual's AUS rate was, the
      lower the rate of malignancy for that AUS cohort was. CONCLUSIONS: Individual
      cytopathologist AUS rates were variable and often exceeded the recommended target
      of 7%. The application of recently published defined diagnostic criteria, along
      with directed cytopathologist feedback, may reduce observer variability and
      appropriately lower AUS utilization.

PMID- 22156460
TI  - Spectrum of risk of malignancy in subcategories of 'atypia of undetermined
      significance'.
AB  - OBJECTIVE: To determine if focal 'nuclear atypia' or 'microfollicular
      architecture' portends a higher risk of malignancy than other subcategories of
      atypia of undetermined significance (AUS) in thyroid fine-needle aspirations
      (FNAs). STUDY DESIGN: The frequencies of The Bethesda System for Reporting
      Thyroid Cytopathology (TBSRTC) categories were calculated from 3,956 thyroid FNAs
      interpreted over a 26-month period at The Johns Hopkins Hospital after adoption
      of TBSRTC. TBSRTC criteria were applied strictly. The risk of malignancy,
      specifically for AUS subcategories, was analyzed by cyto-histo correlation.
      RESULTS: Of the 133 cases diagnosed as AUS, 32% were found to have stageable
      carcinoma (not incidental microcarcinoma) on resection. When the subset of AUS
      with 'nuclear atypia' (AUS-N) was separated from other AUS cases, 48% (30/62) of
      them had stageable carcinoma on resection; of the AUS subset with
      'microfollicular architecture' (AUS-F), 27% (8/30) were malignant on resection.
      The 'suspicious for papillary thyroid carcinoma' (SPTC) group maintained a higher
      risk of malignancy versus AUS-N (relative risk, RR 1.57; 95% CI 1.23-1.81).
      CONCLUSION: The subcategory of 'nuclear atypia' within AUS indicates a higher
      risk of malignancy than other subcategories of AUS but has a lower risk of
      malignancy than SPTC does. Thus, it is an important distinction with potential
      clinical implications.

PMID- 22156461
TI  - Atypical follicular cells with equivocal features of papillary thyroid carcinoma
      is not a low-risk cytologic diagnosis.
AB  - OBJECTIVE: To determine whether or not significant differences in the risk of
      malignancy exist between subgroups of atypical follicular cells in The Bethesda
      System for Reporting Thyroid Cytology (TBSRTC) in patients who underwent surgical
      resection. STUDY DESIGN: Between 2004 and 2009, consecutive thyroid fine-needle
      aspirates at our institutions with a cytologic diagnosis of 'atypical follicular
      cells' were retrieved and subclassified using the diagnosis and diagnostic
      comment as: (1) atypical follicular cells with equivocal features of papillary
      carcinoma [cannot exclude papillary thyroid carcinoma (PTC)] and (2) atypical
      follicular cells, other patterns. The risks of malignancy for excised nodules
      were calculated and comparisons were made between these subgroups. Categorical
      analysis was performed using a 2-tailed Fisher's exact test, and p < 0.05 was
      considered statistically significant. RESULTS: A total of 7,072 thyroid fine
      needle aspiration cases were retrieved, with 1,542 (21.8%) having a histologic
      follow-up. There were 222 (3.1%) cases of 'atypical follicular cells', with 127
      (57.2%) having a histologic correlation and 33 having confirmed malignancies.
      Atypical follicular cells, cannot exclude PTC, have a significantly higher risk
      of malignancy than atypical follicular cells, other patterns (45.8 vs. 13.9%, p <
      0.01). CONCLUSIONS: Atypical follicular cells with equivocal features of
      papillary carcinoma is not a low-risk cytologic diagnosis.

PMID- 22156462
TI  - Cytologic features of focal papillary thyroid carcinoma arising within follicular
      adenoma: a masked cytomorphologic analysis of 17 cases.
AB  - BACKGROUND/OBJECTIVE: Focal papillary thyroid carcinoma (PTC) arising within a
      follicular adenoma (PTCFA) represents a clinically significant, but rare,
      histopathologic subset of papillary carcinomas whose cytologic features have not
      been well described. This uncommon presentation of PTC may contribute to a subset
      of thyroid aspirates interpreted as 'atypia of undetermined
      significance/follicular lesion of undetermined significance' (AUS/FLUS). STUDY
      DESIGN: Seventeen fine-needle aspiration biopsy (FNAB) cases diagnosed as 'PTCFA'
      on corresponding surgical excision were identified from the archival records of 2
      large academic medical centers. A control group of 40 FNAB comprised of 20
      follicular adenomas (FA) and 20 PTC was identified (based on the corresponding
      surgical pathology diagnosis) for comparison. All 57 FNAB were reviewed in a
      masked fashion and scored for a series of 31 cytomorphologic features. The
      intraclass correlation between diagnostic categories and overall agreement
      between cytopathologists was statistically evaluated. RESULTS: Aspirates of PTCFA
      were originally diagnosed as 'negative' (n = 3), 'AUS/FLUS' (n = 7), 'suspicious
      for a follicular neoplasm' (n = 3), 'suspicious for malignancy' (n = 3), and
      'malignant' (n = 1). On masked review, the most common cytomorphologic features
      of PTCFA were a nonmacrofollicular cytoarchitectural pattern (71%), medium-large
      cell size (74%), and micronucleoli (79%). Intranuclear pseudoinclusions and a
      papillary architecture were absent in 85 and 88% of the cases, respectively.
      Relative to the 2 control groups, the PTCFA cases demonstrated overlapping
      features between FA and PTC for the majority of the 31 examined cytomorphologic
      features. CONCLUSION: PTCFA represent a rare subset of PTC that is difficult to
      recognize as PTC by FNAB. Most cases exhibit overlapping features between a
      benign thyroid nodule and conventional PTC, and they are often interpreted as
      'AUS/FLUS'.

PMID- 22156463
TI  - Repeatedly nondiagnostic thyroid fine-needle aspirations do not modify malignancy
      risk.
AB  - OBJECTIVE: Thyroid nodules with nondiagnostic (ND) fine-needle aspirations (FNA)
      typically undergo repeat sampling. While repeat FNA is often diagnostic, little
      is known regarding the significance of repeatedly ND aspirates. Limited data
      suggest there is very low, if any, risk of malignancy for repeatedly ND FNAs.
      STUDY DESIGN: We performed a retrospective analysis of ND thyroid FNAs over a
      nearly 6-year period at our institution to further address this question.
      RESULTS: There were 834 ND thyroid FNAs, representing 694 distinct thyroid
      nodules. Repeat FNA was performed after an initial ND aspirate in 52% of cases
      (363/694); 19% (70/363) had at least one additional ND diagnosis on repeat FNA.
      Surgical follow-up was available for 57 cases. Malignancy was identified
      histologically in 21% (9/42) of nodules after a single ND FNA and in 20% (3/15)
      of nodules with 2 or more repeatedly ND aspirates. Accounting for all benign
      cytologic follow-up, the overall risk of malignancy was 4% [12/303; 3.5% (9/255)
      following a single ND FNA and 6.3% (3/48) after repeated ND FNAs]. CONCLUSION: We
      observed no modification of malignancy risk when repeated FNAs were ND. Clinical
      management for an ND aspirate should remain repeat aspiration along with clinical
      and sonographic correlation.

PMID- 22156464
TI  - Timing of repeat thyroid fine-needle aspiration in the management of thyroid
      nodules.
AB  - OBJECTIVE: The Bethesda System for reporting thyroid fine-needle aspirations
      (FNAs) recommends repeat aspirations be done at least 3 months following the
      initial aspiration to prevent false-positive misinterpretations due to
      reactive/reparative changes. Because limited data exists, we reviewed our own
      data to ascertain the recommendation. STUDY DESIGN: We retrospectively reviewed
      thyroid FNAs accessioned in the Cytology Laboratory at Beth Israel Deaconess
      Medical Center in Boston, Mass., USA, from January 2006 to December 2008. We
      identified patients with repeat aspirates of a single lesion and those with
      thyroidectomy specimens. Cytologic and surgical diagnoses along with time between
      FNAs were recorded. RESULTS: No statistically significant difference was detected
      in the distribution among nondiagnostic, suboptimal, and adequate categories with
      respect to the timing of repeat FNA (p = 0.25). Forty-six percent of the lesions
      that were nondiagnostic/suboptimal initially yielded the same results on repeat.
      Twenty-eight percent of initially adequate specimens were
      nondiagnostic/suboptimal on repeat (p = 0.04). Nine percent of those with an
      initial atypical diagnosis had the same diagnosis on repeat, while 2.6% of those
      who did not have an initial atypical diagnosis had an atypical diagnosis on
      repeat (p = 0.29). False positives between early (16%) and late (12%) repeats
      were not statistically significant (p = 0.74). CONCLUSION: The diagnostic yield
      and accuracy of repeat FNA is independent of the time interval between procedures
      but may be related to the original FNA diagnosis.

PMID- 22156465
TI  - Fine-needle aspiration of mucin-producing thyroid tumors.
AB  - OBJECTIVE: Mucin-producing thyroid tumors are extremely rare. Nonetheless, we
      have encountered three such cases in fine-needle aspiration. We report the
      cytologic and histologic findings and review the literature. STUDY DESIGN:
      Cytologic features were studied on direct smears using Romanovsky stain to detect
      background substance and Papanicolaou stain to analyze nuclear and cytoplasmic
      features. The cytologic features were correlated with histology. Mucin was
      demonstrated by mucicarmine, Alcian Blue/PAS, and Alcian Blue (pH 2.5). RESULTS:
      The cytologic features related to mucin include: (1) thick luminal mucin globules
      and signet ring cells aspirated from an 83-year-old woman with a 3-cm signet ring
      cell follicular adenoma, (2) abundant fluffy mucin containing signet ring cells
      in cohesive fragments aspirated from a 75-year-old man with the bilateral signet
      ring cell follicular variant of papillary carcinoma, which is the first case in
      the English literature, and (3) abundant thin mucoid mucin aspirated from the
      lymph node of an 86-year-old woman with a 5-cm mucinous poorly differentiated
      thyroid carcinoma. CONCLUSION: The occurrence of mucin in thyroid fine-needle
      aspiration does not necessarily indicate metastasis, and the presence of mucin in
      cervical lymph nodes does not exclude the thyroid gland as a possible primary.

PMID- 22156466
TI  - The relationship of cytomorphology of medullary thyroid carcinomas between family
      members with the same RET proto-oncogene mutation.
AB  - OBJECTIVE: To evaluate the relationship of the cytomorphology of medullary
      thyroid carcinomas (MTC) between family members with the same RET proto-oncogene
      mutation. STUDY DESIGN: Review of the fine-needle aspiration slides of 13 cases
      with MTC proven by surgery and pathology from 5 unrelated families with either
      multiple endocrine neoplasia (MEN) type 2A or familial MTC (FMTC). RESULTS:
      Small, round, and abundant large oval-to-polygonal cells were major
      cytomorphologic findings in 66.7% of family members with exon 11, codon 634 TGC 
      > CGC germline mutation. Small, round cells and only a few or no polygonal cells
      were found in 66.7% of family members with exon 11, codon 634 TGC -> TTC germline
      mutation and in 100% of family members with codon 634 TGC -> TGG germline
      mutations, as well as in 100% of family members with exon 10, codon 620 TGC ->
      GGC germline mutation. CONCLUSIONS: The high rate of similarity of cytomorphology
      (66.7-100%) in the family members with MEN type 2A or FMTC might be related to
      the same etiology in the production of MTC in the same family. The relationship
      of the respective cytomorphology with the long-term prognosis is worth
      elucidating further.

PMID- 22156467
TI  - BRAF mutation analysis of fine-needle aspiration biopsies of papillary thyroid
      carcinoma: impact on diagnosis and prognosis.
AB  - OBJECTIVE: The BRAF V600E mutation has been associated with aggressive disease in
      papillary thyroid carcinoma (PTC). Molecular testing has been proposed as a
      useful adjunct to cytology in the diagnosis of malignancy and for tailoring
      clinical management. The aims of our study were to evaluate the BRAF mutational
      status using archived fine-needle aspiration biopsy (FNAB) material from patients
      with long-term follow-up and to correlate it with the original cytology
      diagnosis, clinicopathological stage at surgery, and prognosis. STUDY DESIGN:
      FNAB material from 52 cases of PTC, with a mean follow-up of 8.4 years, was used
      in this study. DNA was extracted from archival cytology slides. Mutation analysis
      was performed by standard sequencing and locked nucleic acid-PCR/sequencing.
      RESULTS: The BRAF V600E mutation was present in 46% of cases, but it was absent
      in all FNABs diagnosed originally as atypical and in 14 of 17 suspicious cases.
      Recurrence was significantly more frequent (p = 0.006) in cases with BRAF
      mutations and 54% of these cases presented with stage 2 or higher. CONCLUSION:
      The BRAF V600E mutation is associated with a higher pathological stage at surgery
      and a higher rate of recurrence. BRAF mutation analysis did not provide a
      significant increase in the accuracy of thyroid FNABs diagnosed as suspicious or
      atypical in our institution.

PMID- 22156468
TI  - BRAF mutation testing of thyroid fine-needle aspiration specimens enhances the
      predictability of malignancy in thyroid follicular lesions of undetermined
      significance.
AB  - BACKGROUND/OBJECTIVE: The Bethesda 2007 Thyroid Cytology Classification defines
      atypia of undetermined significance/follicular lesion of undetermined
      significance (AUS/FLUS) as a heterogeneous category of cases that are neither
      convincingly benign nor sufficiently atypical for a diagnosis of follicular
      neoplasm or suspicious for malignancy. At our institution, we refer to these
      cases as 'indeterminate' and they are further subclassified into two categories.
      BRAF mutation occurs in 40-60% of papillary thyroid carcinoma (PTC). In this
      study, we examined cases in the AUS/FLUS category in correlation with BRAF
      mutation analysis and surgical pathology outcome. STUDY DESIGN: Thyroid fine
      needle aspiration (FNA) cytology specimens interpreted as 'indeterminate' were
      selected from our files, and available remnants of thin-layer processed specimens
      were used for BRAF mutation analysis. Surgical pathology reports were reviewed
      for the final outcomes in these patients. RESULTS: Of the 84 indeterminate cases
      with BRAF mutation analysis, only 49 had follow-up with surgical intervention.
      Sixteen cases had BRAF mutation. All of the BRAF-positive cases had a final
      diagnosis of PTC. CONCLUSIONS: The sensitivity and specificity of BRAF mutation
      in detecting PTC in FNA specimens with indeterminate diagnosis was 59.3 and 100%,
      respectively, while the positive and negative predictive values were 100 and
      65.6%, respectively. The limited data supports the use of BRAF mutation analysis
      to predict the risk of malignancy in patients with indeterminate thyroid FNAs.

PMID- 22156469
TI  - Allele-specific PCR with competitive probe blocking for sensitive and specific
      detection of BRAF V600E in thyroid fine-needle aspiration specimens.
AB  - OBJECTIVE: To detect BRAF V600E mutation in thyroid fine-needle aspiration (FNA)
      slides and needle rinses (NR). STUDY DESIGN: Tumor-enriched DNA was extracted
      from FNA smears, formalin-fixed paraffin-embedded (FFPE) sections, or NR
      specimens from 37 patients with confirmed papillary thyroid carcinoma or benign
      findings. An allele-specific primer selectively amplified the 1799 T>A BRAF
      mutation while simultaneously blocking amplification of wild-type (WT) BRAF with
      an unlabeled probe during PCR. Mutation detection was accomplished by melting
      analysis of the probe. RESULTS: Allele-specific/blocking probe PCR confirmed the
      BRAF mutation status for 20 of 24 paired FNA/FFPE samples previously tested by
      fluorescent probe real-time PCR. For the other 4 cases, the sensitive PCR method
      detected the BRAF mutation in all paired FNA/FFPE samples. Previously, the
      mutation had been detected in only the FFPE samples. The BRAF mutation was also
      detected in some NR specimens. CONCLUSION: Treatment of patients with thyroid
      nodules is guided by FNA biopsy, which can be scantly cellular, necessitating a
      sensitive test that can detect low levels of BRAF V600E mutation in a WT
      background. We report increased detection of BRAF V600E in FNA specimens using
      allele-specific/blocking probe PCR, which has an analytical sensitivity of 0.01%.

PMID- 22156470
TI  - Application of magnetic-resonance-spectroscopy- based metabolomics to the fine
      needle aspiration diagnosis of papillary thyroid carcinoma.
AB  - OBJECTIVE: This study explores the potential use of high-resolution magic angle
      spinning proton magnetic resonance spectroscopy as an ancillary diagnostic
      technique for papillary thyroid carcinoma in thyroid fine-needle aspiration
      biopsies. The method has already been shown to be effective in the classification
      of various other nonthyroid cancers. STUDY DESIGN: Twenty-six samples (13 paired
      cytologic and histologic samples) from patients being evaluated for thyroid
      abnormalities at the Massachusetts General Hospital were spectroscopically
      analyzed, and included: papillary thyroid carcinomas (n = 4), follicular adenomas
      (n = 4), and normal thyroid samples (n = 5). Metabolic profiles were
      statistically generated based on the spectroscopy results, which were then
      correlated with the final cytologic and histologic diagnoses from the same
      samples to determine the diagnostic capacity of the profiles. RESULTS: Principal
      component analysis of the tissue samples revealed statistically significant
      correlations among principal components and various cytologic and histologic
      features. Canonical score 1, calculated with principal components in correlation
      with analyzed pathologies, revealed the ability of the metabolic profile to
      differentiate all three examined histologic tissue groups (ANOVA, p < 0.0001).
      Applying coefficients of principal components and canonical scores obtained with
      tissue samples directly onto spectral results of cytology samples, the calculated
      canonical score 1 also revealed similar trends among the three fine-needle
      aspiration biopsy groups. In particular, the papillary thyroid carcinoma group
      exhibited significant differences from both the adenomatous and normal cytology
      groups (p < 0.0170). CONCLUSIONS: The results indicate the potential of high
      resolution magic angle spinning proton magnetic resonance spectroscopy as an
      ancillary marker for papillary thyroid carcinoma in fine-needle aspiration biopsy
      specimens.

PMID- 22156471
TI  - Histone deacetylase inhibition decreases proliferation and potentiates the effect
      of ionizing radiation in atypical teratoid/rhabdoid tumor cells.
AB  - Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant central nervous
      system neoplasm that primarily occurs in children less than 3 years of age.
      Because of poor outcomes with intense and toxic multimodality treatment, new
      therapies are urgently needed. Histone deacetylase inhibitors (HDIs) have been
      evaluated as novel agents for multiple malignancies and have been shown to
      function as radiosensitizers. They act as epigenetic modifiers and lead to re
      expression of inappropriately repressed genes, proteins, and cellular functions.
      Because of the underlying chromatin remodeling gene mutation in ATRT, HDIs are
      ideal candidates for therapeutic evaluation. To evaluate the role of HDIs against
      ATRT in vitro, we assessed the effect of drug treatment on proliferation,
      apoptosis, and gene expression. In addition, we examined HDI pretreatment as a
      radiosensitization strategy for ATRT. 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium with phenazine
      methosulfate electron coupling reagent (MTS) and clonogenic assays demonstrated
      that HDI treatment significantly reduces the proliferative capacity of BT-12 and
      BT-16 ATRT cells. In addition, the HDI SNDX-275 was able to induce apoptosis in
      both cell lines and induced p21(Waf1/Cip1) protein expression as measured by
      Western blot. Evaluation of differential gene expression by microarray and
      pathway analysis after HDI treatment demonstrated alterations of several key ATRT
      cellular functions. Finally, we showed that HDI pretreatment effectively
      potentiates the effect of ionizing radiation on ATRT cells as measured by
      clonogenic assay. Our findings suggest that the addition of HDIs to ATRT therapy
      may prove to be beneficial, especially when administered in combination with
      current treatment modalities, such as radiation.

PMID- 22156472
TI  - Social reward dependence and brain white matter microstructure.
AB  - People show consistent differences in their cognitive and emotional responses to
      environmental cues, manifesting, for example, as variability in social reward
      processing and novelty-seeking behavior. However, the neurobiological foundation
      of human temperament and personality is poorly understood. A likely hypothesis is
      that personality traits rely on the integrity and function of distributed
      neurocircuitry. In this diffusion tensor imaging (DTI) study, this hypothesis was
      tested by examining the associations between reward dependence (RD) and novelty
      seeking (NS), as measured by Cloninger's Temperament and Character Inventory, and
      fractional anisotropy (FA) and mean diffusivity (MD) as DTI-derived indices of
      white matter (WM) microstructure across the brain. The results supported the
      hypothesis. RD was associated with WM architecture coherence as indicated by a
      negative correlation between RD and FA in frontally distributed areas including
      pathways connecting important constituents of reward-related neurocircuitry. The
      associations between RD and FA could not be explained by age, sex, alcohol
      consumption, or trait anxiety. In contrast, no effects were observed for NS.
      These findings support the theory that WM fiber tract properties modulate
      individual differences in social reward processing.

PMID- 22156474
TI  - Matrix-assisted laser desorption/ionization imaging mass spectrometry: a
      promising technique for reproductive research.
AB  - Matrix-assisted laser desorption/ionization (MALDI) tissue imaging mass
      spectrometry is particularly promising among the numerous applications of mass
      spectrometry. It is used for probing and analyzing the spatial arrangement of a
      wide range of molecules, including proteins, peptides, lipids, drugs, and
      metabolites, directly in thin slices of tissue. In the field of proteomics, the
      technology avoids tedious and time-consuming extraction and fractionation steps
      classically required for sample analysis. MALDI imaging mass spectrometry is
      increasingly recognized as a powerful method for clinical proteomics,
      particularly in cancer research. The technology has particular potential for the
      discovery of new tissue biomarker candidates, classification of tumors, early
      diagnosis or prognosis, elucidating pathogenesis pathways, and therapy
      monitoring. Over recent years, MALDI imaging mass spectrometry has been used for
      molecular profiling and imaging directly in male and female reproductive tissues.
      This review will consider some of the recent publications in the field,
      addressing a range of issues covering embryo development, gene expression product
      profiling during gametogenesis, and seeking and identifying biomarkers of
      reproductive cancers. The wealth of advances in mass spectrometry imaging will
      inevitably attract biologists and clinicians as the advantages and power of this
      technology become more widely known. This review will also discuss bottlenecks
      and the many technical issues that remain to be resolved before laboratories in
      the field can adopt the technology. We foresee that MALDI imaging mass
      spectrometry will have a major impact in reproductive research by opening new
      avenues to the understanding of various molecular mechanisms and the diagnosis of
      reproductive pathologies.

PMID- 22156473
TI  - Advanced glycation end-products as markers of aging and longevity in the long
      lived Ansell's mole-rat (Fukomys anselli).
AB  - Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced
      by reproductive status with breeders far outliving nonbreeders. This raises the
      important question of whether increased longevity of the breeders is reflected in
      atypical expression of biochemical markers of aging. Here, we measured markers of
      glycation and advanced glycation end-products formed in insoluble skin collagen
      of Ansell's mole-rat Fukomys anselli as a function of age and breeding status.
      Glucosepane, pentosidine, and total advanced glycation end-product content
      significantly increased with age after correction for breeder status and sex.
      Unexpectedly, total advanced glycation end-products, glucosepane, and
      carboxymethyl-lysine (CML) were significantly higher in breeders versus
      nonbreeders suggesting that breeders have evolved powerful defenses against
      combined oxidant and carbonyl stress compared with nonbreeders. Most
      interestingly, when compared with other mammals, pentosidine formation rate was
      lower in mole-rat compared with other short-lived rodents confirming previous
      observations of an inverse relationship between longevity and pentosidine
      formation rates in skin collagen.

PMID- 22156475
TI  - Involvement of classical bipartite/karyopherin nuclear import pathway components
      in acrosomal trafficking and assembly during bovine and murid spermiogenesis.
AB  - This study arose from our finding that SubH2Bv, a histone H2B variant residing in
      the subacrosomal compartment of mammalian spermatozoa, contains a bipartite
      nuclear localization signal (bNLS) but in spite of this did not enter the
      spermatid nucleus. Instead, it associated with proacrosomic and acrosomic
      vesicles, which were targeted to the nuclear surface to form the acrosome. On
      this basis we proposed that SubH2Bv targets proacrosomic/acrosomic vesicles from
      the Golgi apparatus to the nuclear envelope by utilizing the classical
      bipartite/karyopherin alpha (KPNA) nuclear import pathway. To test the protein's
      nuclear targeting ability, SubH2Bv, with and without targeted mutations of the
      basic residues of bNLS, as well as bNLS alone, were transfected into mammalian
      cells as GFP-fusion proteins. Only the intact bNLS conferred nuclear entry.
      Subsequently, we showed that a KPNA, most likely KPNA6, occupies the same sperm
      head compartment and follows the same pattern of acrosomal association during
      spermiogenesis as SubH2Bv. Sperm head fractionation combined with Western
      blotting located this KPNA to the subacrosomal layer of the perinuclear theca,
      while immunocytochemistry of testicular sections showed that it associates with
      the surface of proacrosomic/acrosomic vesicles during acrosomal biogenesis. The
      identical sperm-localization and testicular-expression patterns between KPNA and
      SubH2Bv suggested a potential binding interaction between these proteins. This
      was supported by recombinant SubH2Bv affinity pull-down assays on germ cell
      extracts. The results of this study provide a compelling argument that these two
      nuclear homing proteins work in concert to direct the acrosomic vesicle to the
      nucleus. Their final residence in the subacrosomal layer of the perinuclear theca
      of spermatozoa indicates a role for SubH2Bv and KPNA in acrosomal-nuclear
      docking.

PMID- 22156476
TI  - Liver x receptor modulation of gene expression leading to proluteolytic effects
      in primate luteal cells.
AB  - The expressions of genes involved in cholesterol efflux increase, whereas those
      involved in extracellular cholesterol uptake decrease, during spontaneous
      functional regression of the primate corpus luteum (CL). This may result from
      liver x receptor (LXR) alpha (official symbol NR1H3) and/or beta (official symbol
      NR1H2) control of luteal gene transcription, because these nuclear receptor
      superfamily members are key regulators of cellular cholesterol homeostasis.
      Therefore, studies were conducted to assess endogenous LXR ligands in the primate
      CL through the luteal phase, and to determine the effect of synthetic or natural
      LXR ligands on cholesterol efflux and uptake in functional primate luteal cells.
      Using high-performance liquid chromatography tandem mass spectrometry, three LXR
      ligands were identified and quantified in the rhesus macaque CL, including 22R
      hydroxycholesterol (22ROH), 27-hydroxycholesterol (27OH), and desmosterol. Levels
      of 22ROH paralleled serum progesterone concentrations, whereas mean levels of
      27OH tended to be higher following the loss of progesterone synthesis.
      Desmosterol was present throughout the luteal phase. Functional macaque luteal
      cells treated with the synthetic LXR agonist T0901317 or physiologically relevant
      concentrations of the endogenous luteal ligands 22ROH, 27OH, and desmosterol had
      increased expression of various known LXR target genes and greater cholesterol
      efflux. Additionally, T0901317 reduced low-density lipoprotein receptor protein
      and extracellular low-density lipoprotein uptake, whereas 27OH decreased low
      density lipoprotein receptor protein, most likely via a posttranslational
      mechanism. Collectively, these data support the hypothesis that LXR activation
      causes increased cholesterol efflux and decreased extracellular cholesterol
      uptake. In theory, these effects could deplete the primate CL of cholesterol
      needed for steroidogenesis, ultimately contributing to functional regression.

PMID- 22156477
TI  - Endometrial decidualization does not trigger the blood pressure decline of normal
      early pregnancy in mice.
AB  - A drop in mean arterial pressure (MAP) characterizes early, normal pregnancies of
      humans and of inbred mice, species with hemochorial placentation. Murine MAP,
      assessed by continuous radiotelemetry, falls from implantation to Gestation Day 9
      (GD9) and then recovers. The change in the trajectory of mouse MAP after GD9
      coincides with full maturity of the placenta and onset of its circulation. To
      identify whether these early gestational changes in hemodynamic function are
      conceptus and/or maternally regulated, pseudopregnancy (conceptus absent) with
      endometrial decidualization was established in radio transmitter-implanted,
      randomly bred CD1 mice. To avoid destabilization of MAP by anesthesia and
      surgery, decidualization was induced by transcervical infusion of concanavalin A
      coated Sepharose beads 48 h after the female had copulated with a vasectomized
      male. In comparison to the postimplantation drop in MAP recorded in CD1 females
      mated by fertile males, pseudopregnancy MAP was stable to Gestation-Equivalent
      Day 10 in mice with confirmed endometrial decidualization at euthanasia. Thus,
      decidualization, with its accompanying pregnancy-like endocrine environment and
      uterine neoangiogensis and immune cell recruitment, is inadequate to depress
      early postimplantation MAP. These data suggest that the physiological modulation
      of early gestational MAP is not driven by maternal changes but is altered through
      conceptus-based mechanisms.

PMID- 22156478
TI  - Tailor-made therapy for viral hepatitis: recent advances.
AB  - Combination therapy of pegylated interferon-alpha with ribavirin (PEG-IFN/RBV) is
      a standard of care for chronic hepatitis C (CHC). The majority of CHC patients
      are infected with HCV genotype I. The recent discovery revealed by a genome-wide
      association study technology provides the important role of interleukin-28B
      (IL28B) and inosine triphosphatase (ITPA) in HCV infection. In addition, response
      to PEG-IFN/RBV therapy is correlated with insulin resistance, hepatic steatosis,
      and hepatic fibrosis in CHC patients. Double-filtration plasmapheresis together
      with IFN therapy has proved to be effective in the reduction of viral load during
      the early stage of treatment. In CHC patients, not only IL28B status, but also
      the treatment period of PEG-IFN/RBV is important. Even when new
      polymerase/protease inhibitors are introduced in the treatment of CHC, tailor
      made treatment for CHC using IL28B, inosine triphosphatase testing or double
      filtration plasmapheresis treatment prolonged treatment strategy is highly
      recommended. The relative etiologic role of prior hepatitis B virus infection in
      the development of non-B non-C hepatocellular carcinoma is also known in
      hepatitis B-endemic areas.

PMID- 22156479
TI  - Correlation between insulin resistance and outcome of pegylated interferon and
      ribavirin therapy, hepatic steatosis, hepatic fibrosis in chronic hepatitis C-1b
      and high viral load.
AB  - BACKGROUND/AIMS: Insulin resistance (IR) has been reported to be an independent
      predictor of treatment outcome in chronic hepatitis C patients. METHODS: We
      analyzed the relationship between IR and the outcome of pegylated interferon and
      ribavirin (PEG-IFN/RBV) therapy, taking into account host factors of body mass
      index and histological index, such as rate of fatty change and fibrosis. Japanese
      patients (n = 30; 19 men and 11 women; median age 60.0 +/- 8.7 years) with
      chronic hepatitis C-1b with a high viral load were treated with PEG-IFN
      alpha2b/RBV for 48 weeks. RESULTS: Sustained virological response (SVR) was seen
      in 60% (18/30) and non-SVR in 40% (12/30). HOMA-IR (homeostasis model of
      assessment-insulin resistance index) at the start and at 24 weeks of treatment
      showed no statistical difference between SVR and non-SVR. Correlation was
      observed between HOMA-IR and body mass index (r = 0.45, p = 0.013). Among 20
      patients, steatosis and fibrosis were assessed by biopsy. Correlation was
      observed between HOMA-IR and steatosis (r = 0.57, p = 0.0093), whereas no
      correlation was observed between HOMA-IR and fibrosis. CONCLUSION: A larger
      prospective study is needed to clarify the role of IR in the outcome of PEG
      IFN/RBV combination therapy and hepatic fibrosis in Japanese patients.

PMID- 22156480
TI  - Double-Filtration Plasmapheresis plus Interferon-beta for HCV-1b Patients with
      Non-Sustained Virological Response to Previous Combination Therapy.
AB  - BACKGROUND AND AIMS: Double-filtration plasmapheresis (DFPP) together with
      interferon (IFN) administration produces a substantial reduction in the viral
      load during the early stages of treatment. METHODS: Based on their responses to
      previous pegylated IFN and ribavirin (PEG-IFN/RBV) therapy, 20 patients were
      divided into null virological response (NVR; n = 12) and relapse (n = 8) groups.
      DFPP was used in combination with IFN-beta/RBV with subsequent administration of
      PEG-IFN-alpha2a/RBV therapy (DFPP + IFN-beta/RBV then PEG-IFN/RBV). Early viral
      dynamics was assessed, focusing especially on complete early virological response
      (cEVR) associated with sustained virological response. Additionally, the
      interleukin 28B gene, the IFN/RBV resistance-determining region, the IFN
      sensitivity-determining region and the core regions were analyzed. RESULTS: Rapid
      virological response was achieved in 0% (0/12) of NVR and in 75% (6/8) of relapse
      patients, with a significant difference between the two groups (p = 0.001).
      Similarly, cEVR was achieved in 8% (1/12) of NVR and in 88% (7/8) of relapse
      patients, with a significant difference between the two groups (p = 0.037). By
      multivariate logistic regression analysis, interleukin-28B major was a
      significant determiner of cEVR (odds ratio = 24.19, p = 0.037). CONCLUSION: DFPP
      + IFN-beta/RBV then PEG-IFN/RBV therapy is indicated more for relapse than for
      NVR patients.

PMID- 22156481
TI  - Relative etiological role of prior hepatitis B virus infection and nonalcoholic
      fatty liver disease in the development of non-B non-C hepatocellular carcinoma in
      a hepatitis B-endemic area.
AB  - BACKGROUND AND AIMS: We investigated the relative etiological role of prior
      hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) in
      the development of non-B non-C, non-alcohol or specific cause-related
      hepatocellular carcinoma (NBNC-NA-NS HCC) in an HBV-endemic area of Korea.
      METHODS: A total of 329 patients with NBNC-NA-NS HCC were enrolled in this study.
      Prior HBV infection was defined as the presence of isolated IgG hepatitis B core
      antibody (anti-HBc), and NAFLD was diagnosed by the findings from the imaging in
      the absence of a history of excessive alcohol consumption. RESULTS: Prior HBV
      infection was the most common cause of underlying liver disease (76.6%). Only
      8.2% of the patients had NAFLD as the only risk factor and the same proportion of
      patients had evidence of both prior HBV infection and NAFLD. Patients without
      definitive causes accounted for 7.0% of the cases. During the past 10 years, the
      relative proportion of isolated IgG anti-HBc-positive HCC decreased significantly
      from 86.6% in 2001-2005 to 67.4% in 2006-2010 (p < 0.0001) and that of NAFLD
      related HCC increased from 3.8% to 12.2% in the same period, respectively (p =
      0.008). The mean age of NAFLD-related HCC patients (67.3 years) was significantly
      older than that of HCC patients related to prior HBV infection (61.2 years, p <
      0.001). CONCLUSIONS: NAFLD-related HCC increased significantly while HCC related
      to prior HBV infection decreased during the past 10 years in an HBV-endemic area
      of Korea; however, the relative etiological role of prior HBV infection was still
      greater than that of NAFLD in the development of NBNC-NA-NS HCC.

PMID- 22156482
TI  - Predictors of HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients.
AB  - BACKGROUND AND AIMS: In chronic hepatitis B virus (HBV) infections, hepatitis B
      surface antigen (HBsAg) seroclearance reportedly occurs at a rate of 0.50-2.26%.
      Several factors were suggested to be associated with seroclearance including age
      and HBeAg negativity. However, there are few studies evaluating whether HBV DNA
      levels are an independent predictor of HBsAg seroclearance. The aim of this study
      was to evaluate the annual HBsAg seroclearance rate and its predictors including
      serum HBV DNA levels in HBeAg-negative chronic hepatitis B patients. METHODS: We
      included 880 HBeAg-negative chronic hepatitis B patients who underwent an
      evaluation of baseline serum HBV DNA levels. We reviewed the electronic charts
      for baseline clinical, biochemical, and virological factors. RESULTS: The median
      age was 50 years, and the follow-up duration was 31 months. The annual rate for
      the HBsAg seroclearance was 1.8%. In multivariable analysis, the probability of
      HBsAg seroclearance was positively associated with old age (p = 0.046), with a
      sustained inactive phase rather than the occurrence of HBeAg-negative hepatitis
      (p = 0.041), and with an initial HBV DNA level <2,000 IU/ml (p = 0.001).
      CONCLUSION: The annual rate for the HBsAg seroclearance in HBeAg-negative chronic
      hepatitis B patients was 1.8%. Old age, sustained inactive phase, and low levels
      of HBV DNA were independent predictors of HBsAg seroclearance.

PMID- 22156483
TI  - Hepatitis B virus serology to predict antiviral response in chronic hepatitis B.
AB  - Since active replication of hepatitis B virus is strongly associated with the
      development of cirrhosis, hepatocellular carcinoma, and liver-related mortality,
      antiviral therapy is aimed at maximal viral suppression. However, as no antiviral
      therapy is perfect due to the emergence of resistant strains and suboptimal
      efficacy in some patients, modifying the treatment strategies for certain
      patients in advance is important through prediction of treatment responses.
      Recently, along with serial monitoring of hepatitis B virus DNA level,
      quantitative analysis of the serologic markers HBsAg (qHBsAg) and HBeAg (qHBeAg)
      has been used to predict responses to antiviral therapy. The clinical usefulness
      of both pretreatment qHBsAg and decline in qHBsAg during treatment was assessed
      in patients treated with pegylated interferon, suggesting that they might be used
      as another criterion to identify good and poor responders. Similarly, in patients
      treated with oral nucleos(t)ide analogues (NAs), the clinical significance of
      qHBsAg has been reported in some studies. However, as the decline in qHBsAg is
      much slower during NA therapy and the data on the use of qHBsAg to predict
      response to NA treatment are very preliminary, its wide application remains to be
      determined. Another serologic marker (qHBeAg) measured at baseline and during
      treatment might be applied for identifying good or poor responders to antiviral
      therapy. Unfortunately, measurement of qHBeAg has not been widely used because it
      is expensive, nonstandardized, and unavailable in patients with HBeAg-negative
      chronic hepatitis B (CHB). In conclusion, serologic markers may be potential
      predictors of response to antiviral therapy in CHB, allowing delivery of the most
      appropriate treatments to the most suitable patients. Further investigations into
      the universal clinical usefulness of such markers are needed.

PMID- 22156484
TI  - HLA-DRB1*010101 allele is closely associated with poor virological response to
      lamivudine therapy in patients with chronic hepatitis B.
AB  - BACKGROUND/AIMS: We intended to evaluate the association between specific human
      leukocyte antigen (HLA)-DRB1 gene polymorphism and antiviral response to
      lamivudine (LAM) therapy in chronic hepatitis B (CHB) patients. METHODS: Six
      digit HLA-DRB1 genotypes were determined using sequence-based typing in 334 CHB
      patients initially treated with LAM for at least 12 months. Antiviral response
      was evaluated every 3-6 months during LAM therapy. RESULTS: Median age of the
      subjects was 43 years (range, 16-72). Median duration of LAM therapy was 69
      months (range, 13-140). Median baseline serum hepatitis B virus (HBV DNA) level
      was 7.0 log(10) copies/ml (range, 5.5-9.1). At 12 months of LAM therapy, serum
      HBV DNA was undetectable by solution hybridization method in 308 (88%) patients.
      Among 25 HLA-DRB1 alleles identified, HLA-DRB1*090102, *080302, and *070101 were
      the most frequent alleles (>10%). HLA-DRB1*010101 was identified in 5.4%
      (18/334). The frequency of the HLA-DRB1*010101 allele was significantly lower in
      patients with virological response at 12 months of LAM therapy than in patients
      without it (4.2 vs. 19.2%, p = 0.025). The other HLA-DRB1 alleles were not
      associated with virological response. HBeAg loss/seroconversion and alanine
      aminotransferase normalization were not associated with HLA-DRB1 alleles.
      CONCLUSION: The HLA-DRB1*010101 allele is closely associated with poor
      virological response to initial LAM therapy in CHB patients.

PMID- 22156485
TI  - Clinical characteristics of non-B non-C hepatocellular carcinoma: a single-center
      retrospective study.
AB  - BACKGROUND/AIMS: To clarify risk factors and clinical features of both hepatitis
      B surface antigen and anti-HCV negative hepatocellular carcinoma (NBNC-HCC).
      METHODS: HCC patients (n = 1,109) diagnosed at a single center were categorized
      based on the presence of serum hepatitis B surface antigen and HCVAb. Clinical
      characteristics of 127 NBNC-HCC patients were evaluated. RESULTS: NBNC-HCC
      patients were stratified as those with alcoholic liver disease (ALD-HCC, n = 42)
      and alcohol-unrelated liver disease (non-ALD-HCC, n = 85). Compared with the ALD
      HCC group, the non-ALD-HCC group had a higher prevalence of diabetes (p = 0.015),
      larger tumor size (p = 0.007), and higher tumor marker levels (p = 0.014). Liver
      function results were significantly worse in ALD-HCC than in non-ALD-HCC.
      Although the ALD-HCC group had a higher tendency toward recurrence than the non
      ALD-HCC group, survival rates were similar between groups (p = 0.352).
      CONCLUSION: Alcohol consumption was the most common etiologic factor for NBNC
      HCC, and diabetes may be related to the development of HCC in non-ALD-HCC
      patients. Non-ALD-HCC tended to be diagnosed at a more advanced stage, whereas
      liver function was worse, and tumor recurrence rate was higher in ALD-HCC
      patients. Further examination of the risk factors and establishment of a precise
      surveillance system are necessary for early diagnosis and the development of
      curative therapies for NBNC-HCC.

PMID- 22156486
TI  - Interleukin28B and inosine triphosphatase help to personalize hepatitis C
      treatment.
AB  - In the therapy using a combination of pegylated interferon-alpha and ribavirin
      (PEG-IFN/RBV) for chronic hepatitis C (CHC), approximately 50% of CHC patients
      infected with high viremia of HCV genotype 1 reached sustained viral response.
      The recent discovery revealed by a genome-wide association study technology
      provides the unexpected role of IL28B and inosine triphosphatase (ITPA) in HCV
      infection. The former single nucleotide polymorphisms (SNPs) around the IL28B
      gene could improve the diagnostics on the prediction of spontaneous clearance and
      the response to anti-HCV treatment, suggesting that these findings could be
      strong evidence to enhance the development of a novel therapeutic strategy and
      the basic study of IFN-lambdas. Interestingly, the discovered IL28B SNPs revealed
      the enigma that the viral clearance rate was dependent on ethnicity. The latter
      functional SNP in ITPA locus was the most significant SNP associated with RBV
      induced anemia as well as IFN-induced thrombocytopenia. Note that severe Hb
      decline, which is mainly found in ITPA-CC patients, was inversely correlated with
      platelet reduction, contributing to an association between severe anemia and
      relative reactive increase in platelet count. These data may provide a valuable
      pharmacogenetic diagnostic tool for tailoring PEG-IFN/RBV dosing to minimize drug
      induced adverse events and for further optimization of clinical anti-HCV
      chemotherapeutics.

PMID- 22156487
TI  - Association of interleukin-28B and hepatitis C genotype 1 with a high viral load
      and response to pegylated interferon plus ribavirin therapy.
AB  - BACKGROUND: Pegylated interferon (PEG-IFN) plus ribavirin therapy is the current
      standard treatment for chronic hepatitis C (CHC) genotype 1 with high viral load.
      A common genetic variation near the IL28B gene has been found to affect the
      response to PEG-IFN plus ribavirin therapy for CHC. The aims of this study were
      to analyze the association between the rs8099917 genotype and treatment response
      in a cohort study of CHC. METHODS: This study evaluated clinical and laboratory
      parameters retrospectively in a cohort of 122 patients with chronic hepatitis C
      with genotype 1 and a high viral load who received PEG-IFN plus ribavirin
      therapy. We carried out univariate and multivariate statistical analyses of
      parameters and clinical responses. RESULTS: Sixty-three of 122 patients (51.6%)
      had sustained virological responses (SVRs). Patients with the rs8099917 genotype
      TT achieved significantly higher SVR rates (p < 0.01). Univariate analysis
      revealed that SVRs were associated with BMI, fibrosis, albumin, total
      cholesterol, PEG-IFN dose, ribavirin dose and the rs8099917 genotype.
      Multivariate analysis revealed that the rs8099917 genotype (odds ratio 7.434, 95%
      CI 2.278-24.257, p = 0.001) and total PEG-IFN dose (odds ratio 7.162, 95% CI
      1.565-18.15, p = 0.007) were significant factors. CONCLUSIONS: The rs8099917
      genotype and total PEG-IFN dose were associated with SVR in patients with
      hepatitis C virus genotype 1.

PMID- 22156489
TI  - Exon arrays reveal alternative splicing aberrations in Parkinson's disease
      leukocytes.
AB  - BACKGROUND: Parkinson's disease (PD) is the second most frequent
      neurodegenerative disease worldwide. Clinical diagnosis can only be made when the
      vast majority of the dopaminergic cell population has died. However, the cause(s)
      for sporadic PD is/are yet unclear. Transcript changes have recently been
      described in PD patients' whole blood cells, but corresponding splicing patterns
      remained unknown. OBJECTIVE: To search for alternative splicing aberrations in PD
      patients' blood leukocytes. METHODS: We applied exon microarrays to profile PD
      patients' blood leukocyte mRNA. Exon level splicing analysis served as a basis
      for downstream classification and functional analyses. RESULTS: Patients and
      carefully matched controls were classified by the splicing exon profiles of their
      leukocyte transcripts. Specifically, many exons were downregulated in PD patients
      compared to controls. Functional analysis highlighted aberrant splicing of PD
      related transcripts and impaired NF-kappaB cascade and immune response.
      CONCLUSION: PD patient's blood leukocytes exhibit alternative splicing of
      numerous transcripts. The aberrant alternative splicing in PD patients' blood
      cells has potential implications for early diagnosis and future therapeutics.

PMID- 22156488
TI  - Association between increased serum osteoprotegerin levels and improvement in
      bone mineral density after parathyroidectomy in hemodialysis patients.
AB  - Secondary hyperparathyroidism (SHPT) is a common complication in chronic renal
      disease.  Osteoprotegerin (OPG), an extracellular cytokine receptor secreted by
      osteoblasts, can promote bone formation by inhibiting the function of
      osteoclasts.  Hemodialysis (HD) patients have elevated serum OPG levels.  OPG
      secretion can be suppressed with high parathyroid hormone (PTH) levels.  HD
      patients with refractory SHPT can benefit from parathyroidectomy (PTX) treatment,
      but the changes of serum OPG, bone turnover markers and bone mineral density
      (BMD) following PTX in HD patients remain unclear.  In this study, patients on
      maintenance HD who received PTX for refractory SHPT (n = 28) were prospectively
      followed for 1 year.  Serum intact PTH (iPTH), alkaline phosphatase (Alk-P), and
      OPG were measured serially; BMD was measured pre-PTX and at 1 year after PTX. 
      After PTX, serum iPTH levels reduced profoundly.  Serum Alk-P levels increased
      rapidly, peaking at 2 weeks post-PTX, while serum OPG levels gradually increased
      at 2 weeks after PTX and peaked at 2 months.  BMD improved in both femoral neck
      (FN; cancellous and cortical bone) and lumbar spine (LS; cancellous bone). 
      Higher baseline iPTH levels were associated with greater FN and LS BMD
      improvements at one year after PTX.  The increment of serum OPG was correlated
      with the increase in LS BMD, implying that inhibition of osteoclastic bone
      resorption may improve BMD within the first year after PTX.  These findings
      suggest that PTX removes the suppressive effects of high PTH on OPG secretion,
      resulting in the increased serum OPG levels that may contribute to BMD
      improvement.

PMID- 22156490
TI  - Population survey of the Philippine tarsier (Tarsius syrichta) in Corella, Bohol.
AB  - In 1986, in response to the rapid habitat destruction throughout the archipelago,
      the Philippine tarsier was classified as endangered. Since that time, this
      tarsier has been reclassified as data deficient and more recently as near
      threatened despite a significant lack of information on the population density of
      the species. Data were collected at the Philippine Tarsier Foundation Sanctuary
      from June to October 2010. Population density was estimated using a modified form
      of the quadrat census method. A total of 55 individuals were located within the
      sampled area. This is equivalent to approximately 1.55 tarsiers per hectare.
      Ecologically, there were significantly more tarsiers found in the young secondary
      forest than in areas characterized as old secondary forest. Extrapolating to the
      entire protected area, as many as 258 tarsiers may reside in the sanctuary. The
      vegetation plots where tarsiers were found had substantially more trees per plot,
      contained trees with larger diameters, and contained slightly taller trees than
      did the plots where no tarsiers were observed.

PMID- 22156491
TI  - Does hypereosinophilic syndrome precede common B acute lymphoblastic leukaemia in
      childhood? A case report.
AB  - Hypereosinophilic syndrome (HES) and the association of hypereosinophilia with
      acute lymphoblastic leukaemia (ALL) are both rare in children. Some acute
      myelogenous leukaemias can present with eosinophilia, but the relationship
      between HES and ALL is not well known and is rarer than the relationship between
      HES and acute myelogenous leukaemia. Patients are diagnosed with HES when no
      cause is found to explain the eosinophilia leading to end organ damage. For this
      reason, it is recommended that patients presenting with hypereosinophilia be
      carefully assessed to exclude any malignant clonal proliferation. HES may present
      with severe clinical manifestations such as high leucocyte count, anaemia,
      thrombocytopaenia, hepatosplenomegaly or cardiac and neurological involvement,
      all of which are primarily features of myeloproliferative disorders. Some
      patients with HES can develop chronic eosinophilic leukaemia. Successful
      treatment of HES with agents used in chronic myeloid leukaemia supports the idea
      that HES can be a chronic myeloid disorder. There are few cases reporting an
      association between ALL and hypereosinophilia that precedes or is concomitant
      with ALL. Here we report the case of a 14-year-old girl who developed common B
      ALL 7 months after diagnosis and treatment of HES. Interestingly, eosinophilia
      was not concomitant with the diagnosis of ALL.

PMID- 22156492
TI  - Regulatory T cells enhance mast cell production of IL-6 via surface-bound TGF
      beta.
AB  - Mast cell degranulation is a hallmark of allergic reactions, but mast cells can
      also produce many cytokines that modulate immunity. Recently, CD25(+) regulatory
      T cells (Tregs) have been shown to inhibit mast cell degranulation and
      anaphylaxis, but their influence on cytokine production remained unknown. In this
      study, we show that, rather than inhibit, Tregs actually enhance mast cell
      production of IL-6. We demonstrate that, whereas inhibition of degranulation was
      OX40/OX40 ligand dependent, enhancement of IL-6 was due to TGF-beta.
      Interestingly, our data demonstrate that the Treg-derived TGF-beta was surface
      bound, because the interaction was contact dependent, and no TGF-beta was
      detectable in the supernatant. Soluble TGF-beta1 alone was sufficient to enhance
      mast cell IL-6 production, and these supernatants were sufficient to promote Th17
      skewing, but those from Treg-mast cell cultures were not, supporting this being
      surface-bound TGF-beta from the Tregs. Interestingly, the augmentation of IL-6
      production occurred basally or in response to innate stimuli (LPS or
      peptidoglycan), adaptive stimuli (IgE cross-linking by specific Ag), and cytokine
      activation (IL-33). We demonstrate that TGF-beta led to enhanced transcription
      and de novo synthesis of IL-6 upon activation without affecting IL-6 storage or
      mRNA stability. In vivo, the adoptive transfer of Tregs inhibited mast cell
      dependent anaphylaxis in a model of food allergy but promoted intestinal IL-6 and
      IL-17 production. Consequently, our findings establish that Tregs can exert
      divergent influences upon mast cells, inhibiting degranulation via OX40/OX40
      ligand interactions while promoting IL-6 via TGF-beta.

PMID- 22156493
TI  - TLR and nucleotide-binding oligomerization domain-like receptor signals
      differentially regulate exogenous antigen presentation.
AB  - The effect of dendritic cell (DC) maturation on MHC class II-restricted Ag
      presentation is well studied, but less is known about the effects of DC
      maturation on MHC class I-restricted cross-presentation. We investigated the
      ability of mature DCs to present Ags from cells infected with HSV-1. Pretreatment
      with pure LPS increased cross-presentation in a manner dependent on both MyD88
      and Toll/IL-1R domain-containing adaptor inducing IFN-beta, whereas a similar
      dose of a less pure LPS preparation inhibited cross-presentation. The difference
      could not be attributed to differences in uptake or phenotypic maturation. The
      likely contaminant responsible for shutting down cross-presentation is
      peptidoglycan (PGN). Addition of PGN to pure LPS abrogated its ability to enhance
      cross-presentation. Direct activation of DCs with PGN inhibited cross
      presentation through nucleotide-binding oligomerization domain-like receptor
      signaling. These results demonstrate that different maturation stimuli can have
      opposite impacts on the ability of DCs to cross-present viral Ags.

PMID- 22156494
TI  - PTP1B deficiency exacerbates inflammation and accelerates leukocyte trafficking
      in vivo.
AB  - It is reported that PTP1B limits cytokine signaling in vitro. However, PTP1B's
      function during inflammation in vivo is not known. In this report, we determined
      whether PTP1B deficiency affects allergic inflammation in vivo. Briefly, lungs of
      OVA-challenged PTP1B(-/-) mice had elevated numbers of eosinophils and eosinophil
      progenitors at 6 h after one OVA challenge and at 24 h after a third OVA
      challenge as compared with OVA-challenged wild-type mice. There was also an
      increase in numbers of CD11b(+)SiglecF(+)CD34(+)IL-5Ralpha(+) eosinophil
      progenitors in the bone marrow, peripheral blood, and spleens of OVA-challenged
      PTP1B(-/-) mice. Intravital microscopy revealed that, in OVA-challenged PTP1B(-/
      ) mice, blood leukocytes rapidly bound to endothelium (5-30 min), whereas, in
      wild-type mice, blood leukocytes bound to endothelium at the expected 6-18 h.
      Consistent with early recruitment of leukocytes, lung eotaxin and Th2 cytokine
      levels were elevated early in the PTP1B(-/-) mice. Interestingly, spleen
      leukocytes from PTP1B(-/-) mice exhibited an increased chemotaxis, chemokinesis,
      and transendothelial migration in vitro. In summary, PTP1B functions as a
      critical negative regulator to limit allergic responses.

PMID- 22156495
TI  - B cell-derived IL-10 does not regulate spontaneous systemic autoimmunity in
      MRL.Fas(lpr) mice.
AB  - B cells contribute to the pathogenesis of chronic autoimmune disorders, like
      systemic lupus erythematosus (SLE), via multiple effector functions. However, B
      cells are also implicated in regulating SLE and other autoimmune syndromes via
      release of IL-10. B cells secreting IL-10 were termed "Bregs" and were proposed
      as a separate subset of cells, a concept that remains controversial. The balance
      between pro- and anti-inflammatory effects could determine the success of B cell
      targeted therapies for autoimmune disorders; therefore, it is pivotal to
      understand the significance of B cell-secreted IL-10 in spontaneous autoimmunity.
      By lineage-specific deletion of Il10 from B cells, we demonstrated that B cell
      derived IL-10 is ineffective in suppressing the spontaneous activation of self
      reactive B and T cells during lupus. Correspondingly, severity of organ disease
      and survival rates in mice harboring Il10-deficient B cells are unaltered.
      Genetic marking of cells that transcribe Il10 illustrated that the pool of IL-10
      competent cells is dominated by CD4 T cells and macrophages. IL-10-competent
      cells of the B lineage are rare in vivo and, among them, short-lived plasmablasts
      have the highest frequency, suggesting an activation-driven, rather than lineage
      driven, phenotype. Putative Breg phenotypic subsets, such as CD1d(hi)CD5(+) and
      CD21(hi)CD23(hi) B cells, are not enriched in Il10 transcription. These genetic
      studies demonstrated that, in a spontaneous model of murine lupus, IL-10
      dependent B cell regulation does not restrain disease and, thus, the pathogenic
      effects of B cells are not detectably counterbalanced by their IL-10-dependent
      regulatory functions.

PMID- 22156496
TI  - Cutting edge: histamine is required for IL-4-driven eosinophilic allergic
      responses.
AB  - Histamine is an important allergic mediator, and studies have defined roles for
      both histamine 1 and 4 receptors in allergic airway inflammation. In this study,
      we show that histamine is necessary to generate IL-4-driven eosinophilic
      inflammation, as histamine-deficient mice cannot generate eosinophilic lung
      inflammation in response to intratracheal IL-4 and exogenous histamine restores
      responsiveness. This is histamine 2 receptor (H2R) dependent because H2R knockout
      mice fail to respond to IL-4, and a H2R agonist restores inflammation in
      histidine decarboxylase knockout. Furthermore, alveolar epithelial cells require
      H2R to produce CCL24, an eosinophil recruitment factor, whereas H2R blockade
      reduces CCL24 production from wild-type cells. In an allergic inflammation model,
      H2R knockout mice show significantly reduced eosinophilic inflammation and CCL24
      expression. These data demonstrate a previously unidentified role for H2R in
      allergic inflammation and establishes a synergy between endogenous histamine and
      IL-4 that supports eosinophilic recruitment to the lung.

PMID- 22156497
TI  - Structural insights into the substrate specificity of human granzyme H: the
      functional roles of a novel RKR motif.
AB  - Human granzyme H (GzmH) is constitutively expressed in human NK cells that have
      important roles in innate immune responses against tumors and viruses. GzmH is a
      chymotrypsin-like serine protease. Its substrate preference and its mechanism of
      substrate recognition are poorly understood. To provide structural insights into
      the substrate recognition mechanisms for GzmH, we solved the crystal structures
      of a D102N-GzmH mutant alone and in complex with a decapeptide substrate and an
      inhibitor to 2.2 A, 2.4 A, and 2.7 A, respectively. The Thr(189), Gly(216), and
      Gly(226) specificity triad in the S1 pocket of GzmH defines its preference for
      bulky, aromatic residues (Tyr and Phe) at the P1 position. Notably, we discovered
      that an unusual RKR motif (Arg(39)-Lys(40)-Arg(41)), conserved only in GzmH,
      helps define the S3' and S4' binding regions, indicating the preference for
      acidic residues at the P3' and P4' sites. Disruption of the RKR motif or the
      acidic P3' and P4' residues in the substrate abolished the proteolytic activity
      of GzmH. We designed a tetrapeptide chloromethylketone inhibitor, Ac-PTSY
      chloromethylketone, which can selectively and efficiently block the enzymatic and
      cytotoxic activity of GzmH, providing a useful tool for further studies on the
      function of GzmH.

PMID- 22156498
TI  - Prophylaxis in recurrent unipolar depression: a new indication for treatment
      studies.
AB  - Antidepressants are used for long periods of time and until recently there were
      no formal requirements for establishing efficacy in the maintenance phase or the
      prophylactic phase of the treatment of depression. The CPMP guidelines advise
      regulatory authorities in the EEC to consider the efficacy of antidepressants in
      the medium and the long term separately from efficacy in the treatment of the
      acute episode. This paper reviews the efficacy of antidepressants in continuation
      treatment and prophylactic treatment of unipolar depression. Prophylactic studies
      are difficult and time consuming and it is important to adopt adequate trial
      methodology. The minimum criteria for the demonstration of prophylactic efficacy
      are presented.

PMID- 22156499
TI  - Functional interactions between D-1 and D-2 dopamine receptor systems: their role
      in the regulation of psychomotor behaviour, putative mechanisms, and clinical
      relevance.

PMID- 22156500
TI  - Anticonflict effects of the 5-HT1A compound flesinoxan.
AB  - The new phenylpiperazine derivative flesinoxan, a potent and selective
      serotonin(1A) (5-HT(1A)) agonist, was examined under a procedure that has proved
      to be a reliable and sensitive method for detecting novel anxiolytic drugs
      believed to produce their effects at the 5-HT( 1A) receptor subtype. Key pecking
      by pigeons was maintained by the presentation of food following every 30th
      response in the presence of a white keylight; during an alternate component,
      correlated with a red keylight, every 30th response produced food and electric
      shock which suppressed responding (punishment). Flesinoxan doses from 0.001 to
      0.3 mg/ kg, intramuscularly, produced significant increases in punished
      responding at doses that did not affect unpunished responding. Doses of
      flesinoxan between 1.0 and 3.0 mg/kg also increased punished responding but
      produced decreases in responding that was not punished. In a second study
      flesinoxan substituted for the 5-HT(1A) anxiolytic buspirone under a drug
      discrimination procedure, providing further evidence that the behavioural effects
      offlesinoxan are mediated by 5-HT(1A) mechanisms. Based on these findings, it
      would appear that flesinoxan should be a useful compound in the clinical
      management of anxiety.

PMID- 22156501
TI  - Antidepressant treatments, including electroconvulsive shock and the putative
      antidepressant sibutramine hydrochloride, do not alter [3H]-prazosin binding to
      rat cortical membranes.
AB  - Treatment for 1, 3 or 10 days with sibutramine hydrochloride (3 mg/kg), desi
      pramine (10 mg/kg), amitriptyline (10 mg/kg) or pargyline (10 mg/kg) did not
      effect the number or affinity of alpha(1)-adrenoceptors as determined by [(3)H]
      prazosin binding to rat cerebral cortical membranes. Similarly, neither single,
      nor repeated (five times over 10 days) electroconvulsive shocks, given under
      halothane anaesthesia had any effect on the parameters of [(3)H]-prazosin
      binding. These data suggest that the clinical actions of these treatments are
      unlikely to involve changes in alpha(1)-adrenoceptor function.

PMID- 22156502
TI  - The scopolamine model of dementia: chronic transdermal administration.
AB  - The transient impairments of memory produced by the muscarinic antagonist
      scopolamine have been adopted as a pharmacological model of Alzheimer-type
      dementia in normal volunteers. In this study we examined the effects of chronic
      (72 h) transdermal administration of scopolamine on memory, attention, sedation
      and visual function. The transdermal patches provided constant plasma levels of
      scopolamine for the duration of the study. Indices of the peripheral effects of
      scopolamine (visual near-point and pupil size) showed impairments that were
      sustained for 3 days. However, measures of sedation and memory revealed
      impairments that were maximal the day after patch application and which were no
      longer present 3 days after application. This pattern of results is discussed in
      relation to pharmacological modelling of Alzheimer's disease.

PMID- 22156503
TI  - Biphasic effects of propranolol on extinction of rewarded responding.
AB  - The effect of propranolol (5 mg/kg intraperitoneally) was investigated on the
      extinction of: (i) lever-pressing reinforced on a random interval (RI 64 s)
      schedule; and (ii) continuously reinforced running (1 min intertrial interval).
      Although there was evidence of an initial effect in each case to facilitate
      responding (increased rate of lever-pressing or speed of running), the opposite
      effect emerged as extinction continued; that is, propranolol promoted extinction.
      These results are inconsistent with the author's hypothesis, suggested by earlier
      studies, that acute administration of propranolol antagonizes the inhibitory
      effects of non- reward on behaviour.

PMID- 22156504
TI  - Temporal factors in drug discrimination: Experiments with nicotine.
AB  - The role of the presession interval (PI) in drug discrimination research has been
      studied in rats trained to discriminate nicotine from saline in a two-bar operant
      conditioning procedure. Different groups of rats were trained at different Pls,
      varying between 5 and 35 min, and tests were then carried out for qualitative and
      quantitative differences between the cues. There was complete generalization from
      nicotine cues trained at one time to tests carried out at other times. The
      sensitivity of the cues at different Pls to the nicotinic antagonist mecamylamine
      was very similar. Generalization to amphetamine was nearly complete when the
      nicotine cue was established with PI of 20-35 min and only partial when the PI
      for the nicotine was 5 min. Thus, there was no clear evidence for any qualitative
      difference between nicotine cues established with different PIs. However, the PI
      influenced quantitative aspects of the nicotine cue in a marked and complex
      manner. Increasing the PI during training produced a two- to three-fold decrease
      in the ED(50), whereas increasing the PI during testing produced a two- to three
      fold increase in the ED(50). This shows that the effects of changing the PIs
      during training and testing were similar in magnitude but opposite in direction.
      These changes in ED(50) values can be explained by pharmacokinetic considerations
      in conjunction with knowledge of the role of training dose in the discrimination
      of nicotine. The quantitative sensitivity of the drug discrimination procedure
      can be substantially influenced by the choice of temporal parameters used in
      training and testing.

PMID- 22156505
TI  - Peptide-dopamine interactions in the central nervous system: implications for
      neuropsychiatric disorders.

PMID- 22156507
TI  - Multimodality treatment with conventional transcatheter arterial
      chemoembolization and radiofrequency ablation for unresectable hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: To evaluate the efficacy of multimodality treatment consisting
      of conventional transcatheter arterial chemoembolization (TACE) and
      radiofrequency ablation (RFA) in patients with non-resectable and non-ablatable
      hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 85
      consecutive patients with HCC (59 solitary, 29 multifocal HCC) received TACE
      followed by RFA between 2001 and 2010. The mean number of tumors per patient was
      1.6 +/- 0.7 with a mean size of 3.0 +/- 0.9 cm. Both local efficacy and patient
      survival were evaluated. RESULTS: Of 120 treated HCCs, 99 (82.5%) showed a
      complete response (CR), while in 21 HCCs (17.5%) a partial response was depicted.
      Patients with solitary HCC revealed CR in 91% (51/56); in patients with
      multifocal HCC (n = 29) CR was achieved in 75% (48 of 64 HCCs). The median
      survival for all patients was 25.5 months. The 1-, 2-, 3- and 5-year survival
      rates were 84.6, 58.7, 37.6 and 14.6%, respectively. Statistical analysis
      revealed a significant difference in survival between Barcelona Clinic Liver
      Cancer (BCLC) A (73.4 months) and B (50.3 months) patients, while analyses failed
      to show a difference for Child-Pugh score, Cancer of Liver Italian Program (CLIP)
      score and tumor distribution pattern. CONCLUSION: TACE combined with RFA provides
      an effective treatment approach with high local tumor control rates and promising
      survival data, especially for BCLC A patients. Randomized trials are needed to
      compare this multimodality approach with a single modality approach for early
      stage HCC.

PMID- 22156506
TI  - Vitamin B12 and homocysteine levels and 6-year change in peripheral nerve
      function and neurological signs.
AB  - BACKGROUND: Low vitamin B12 and high homocysteine (Hcy) levels are common in
      older adults and may be associated with worse neurological function. The aim of
      this study is to determine whether changes in B12 or Hcy levels are associated
      with longitudinal changes in peripheral nerve function and clinical neurological
      signs and symptoms. METHODS: Participants aged 60 years and older at baseline (n
      = 678; 72.2 +/- 6.2 years; 43.5% male) were from the InCHIANTI Study. Low B12
      (<260 pmol/L) and high Hcy (>=13 MUmol/L) were measured at baseline and 3-year
      follow-up. Neurological function was assessed by peroneal nerve conduction
      amplitude (compound motor action potential) and velocity, neurological
      examination, and peripheral neuropathy symptoms at baseline, 3-year, and 6-year
      follow-up. RESULTS: At baseline, 43.8% had low B12 levels and 58.6% had high Hcy
      levels. Over 6 years, 12.4% declined to poor compound motor action potential (<1
      mV) and 42.1% declined to poor nerve conduction velocity (<40 m/s). In mixed
      models analyses, sustained high Hcy was associated with worse compound motor
      action potential compared with sustained normal Hcy (p = .04), adjusting for
      demographics, diabetes, and folate level. Participants whose Hcy level became
      high at follow-up were more likely to become unable to detect monofilament at 6
      year follow-up compared with those with sustained normal Hcy (odds ratio: 5.4;
      95% CI: 1.5-19.0), adjusting for demographics, diabetes, body mass index, and
      peripheral arterial disease. There was no association with vitamin B12 level or
      with symptoms. CONCLUSIONS: High Hcy may be associated with worse sensory and
      motor peripheral nerve function. Because poor nerve function has been associated
      with lower strength and physical performance, these results have important
      implications for disability in older adults.

PMID- 22156508
TI  - Hydrogen saline treatment attenuates hyperoxia-induced retinopathy by inhibition
      of oxidative stress and reduction of VEGF expression.
AB  - OBJECTIVE: Retinal neovascularization or retinopathy is a proliferative disorder
      of the retinal capillaries and is the primary cause of blindness. Some studies
      have shown that oxidative stress plays an important role in hyperoxia-induced
      retinal neovascularization. Previous reports have indicated that hydrogen has a
      therapeutic, antioxidant activity by selectively reducing hydroxyl radicals. This
      study examined the therapeutic effect of hydrogen saline on retinopathy in an
      established mouse model of hyperoxia-induced retinopathy. METHODS: Mouse pups
      were exposed to 75% O(2) from postnatal day 7 (P7) to P12. Hydrogen saline was
      administered by intraperitoneal injection (5 ml/kg) daily for 5 days. On P17, the
      pups were decapitated, and retinal neovascularization was assessed using
      fluorescence imaging and histopathological examination. Vascular endothelial
      growth factor (VEGF) expression was evaluated using real-time polymerase chain
      reaction and fluorescence immunohistochemistry. Oxidative stress was quantified
      based on the malondialdehyde (MDA) level. RESULTS: Hydrogen saline decreased
      retinal neovascularization, reduced the mRNA and protein expression of VEGF, and
      suppressed the MDA levels. CONCLUSIONS: Hydrogen saline may be a potential
      treatment for hyperoxia-induced retinopathy that acts via the inhibition of
      oxidative stress and the reduction of VEGF expression.

PMID- 22156509
TI  - 2011 Recommendations for the diagnosis and management of gout and hyperuricemia.
AB  - Gout is a major health problem in the United States; it affects 8.3 million
      people, which is approximately 4% of the adult population. Gout is most often
      diagnosed and managed in primary care physician practices. Primary care
      physicians have a significant opportunity to diagnose and manage patients with
      gout and improve patient outcomes. Following publication of the 2006 European
      League Against Rheumatism (EULAR) gout guidelines, significant evidence on gout
      has accumulated and new treatments for patients with gout have become available.
      It is the objective of these 2011 recommendations for the diagnosis and
      management of gout and hyperuricemia to update the 2006 EULAR guidelines, paying
      special attention to the needs of primary care physicians, who manage most
      patients with gout. The revised 2011 recommendations are based on the Grading of
      Recommendations Assessment, Development, and Evaluation approach as an evidence
      based strategy for rating quality of evidence and grading strength of
      recommendation in clinical practice. A total of 26 key recommendations for
      diagnosis (n = 10) and management (n = 16) were evaluated. Presence of tophus
      (proven or suspected) and response to colchicine had the highest clinical
      diagnostic value (likelihood ratio [LR], 15.56 [95% CI, 2.11-114.71] and LR, 4.33
      [95% CI, 1.16-16.16], respectively). The key aspect of effective management of an
      acute gout attack is initiation of treatment within hours of onset of first
      symptoms. Low-dose colchicine is better tolerated than and is as effective as
      high-dose colchicine (number needed to treat [NNT], 5 [95% CI, 3-13] and NNT, 6
      [95% CI, 3-72], respectively). For urate-lowering therapy, allopurinol in
      combination with probenecid was shown to be more effective than either agent
      alone (effect size [ES], 5.51 for combination; ES, 4.46 for probenecid; and ES,
      2.80 for allopurinol). Febuxostat, also a xanthine oxidase inhibitor, has a
      slightly different mechanism of action and can be prescribed at unchanged doses
      for patients with mild-to-moderate renal or hepatic impairment. Febuxostat 40 mg
      versus 80 mg (NNT, 6 [95% CI, 4-11]) and 120 mg (NNT, 6 [95% CI, 3-26]) both
      demonstrated long-term efficacy. The target of urate-lowering therapy should be a
      serum uric acid level of <= 6 mg/dL. For patients with refractory and tophaceous
      gout, intravenous pegloticase is a new treatment option.

PMID- 22156510
TI  - Richter syndrome and brain involvement: low-grade lymphoma relapsing as cerebral
      high-grade lymphoma.
AB  - Richter syndrome (RS) describes the development of high-grade non-Hodgkin's
      lymphoma (NHL) from low-grade NHL. RS isolated to the brain is very rare and has
      a poor prognosis. We describe the cases of high-grade large B-cell diffuse NHL in
      a 56-year-old male with chronic lymphocytic leukemia and in a 71-year-old female
      with previously unknown low-grade NHL, both with initial appearance of
      neurological symptoms. This report extends the literature of central nervous
      system RS and particularly highlights the importance of a thorough diagnostic
      evaluation of patients with low-grade NHL presenting with neurological symptoms.

PMID- 22156511
TI  - Software tool for improved prediction of Alzheimer's disease.
AB  - BACKGROUND: Diagnostic criteria of Alzheimer's disease (AD) emphasize the
      integration of clinical data and biomarkers. In practice, collection and analysis
      of patient data vary greatly across different countries and clinics. OBJECTIVE:
      The goal was to develop a versatile and objective clinical decision support
      system that could reduce diagnostic errors and highlight early predictors of AD.
      METHODS: Novel data analysis methods were developed to derive composite disease
      indicators from heterogeneous patient data. Visualizations that communicate these
      findings were designed to help the interpretation. The methods were implemented
      with a software tool that is aimed for daily clinical practice. RESULTS: With the
      tool, clinicians can analyze available patients as a whole, study them
      statistically against previously diagnosed cases, and characterize the patients
      with respect to having AD. The tool is able to work with virtually any patient
      measurement data, as long as they are stored in electronic format or manually
      entered into the system. For a subset of patients from the test cohort, the tool
      was able to predict conversion to AD at an accuracy of 93.6%. CONCLUSION: The
      software tool developed in this study provides objective information for early
      detection and prediction of AD based on interpretable visualizations of patient
      data.

PMID- 22156512
TI  - Family-based association tests using genotype data with uncertainty.
AB  - Family-based association studies have been widely used to identify association
      between diseases and genetic markers. It is known that genotyping uncertainty is
      inherent in both directly genotyped or sequenced DNA variations and imputed data
      in silico. The uncertainty can lead to genotyping errors and missingness and can
      negatively impact the power and Type I error rates of family-based association
      studies even if the uncertainty is independent of disease status. Compared with
      studies using unrelated subjects, there are very few methods that address the
      issue of genotyping uncertainty for family-based designs. The limited attempts
      have mostly been made to correct the bias caused by genotyping errors. Without
      properly addressing the issue, the conventional testing strategy, i.e. family
      based association tests using called genotypes, can yield invalid statistical
      inferences. Here, we propose a new test to address the challenges in analyzing
      case-parents data by using calls with high accuracy and modeling genotype
      specific call rates. Our simulations show that compared with the conventional
      strategy and an alternative test, our new test has an improved performance in the
      presence of substantial uncertainty and has a similar performance when the
      uncertainty level is low. We also demonstrate the advantages of our new method by
      applying it to imputed markers from a genome-wide case-parents association study.

PMID- 22156514
TI  - Natural killer cells regulate murine cytomegalovirus-induced sialadenitis and
      salivary gland disease.
AB  - The transmission of herpesviruses depends on viral shedding at mucosal surfaces.
      The salivary gland represents a major site of persistent viral replication for
      many viruses, including cytomegalovirus. We established a mouse model of salivary
      gland dysfunction after acute viral infection and investigated the cellular
      requirements for the loss of secretion. Murine cytomegalovirus (MCMV) infection
      severely impaired saliva secretion independently of salivary gland virus levels.
      Lymphocytes or circulating monocytes/macrophages were not required for secretory
      dysfunction. Dysfunction occurred before glandular inflammation, suggesting that
      a soluble mediator initiated the disruption of acinar cell function. Despite
      genetic differences in innate resistance to MCMV, NK cells protected the host
      against acinar atrophy and the loss of secretions under conditions of an
      exceedingly low virus inoculum. NK cells also modulated the type of glandular
      inflammation after infection, as they prevented an influx of Siglec-F(+)
      polymorphonuclear leukocytes (PMNs). Therefore, beyond their recognized role in
      controlling MCMV replication, NK cells preserve organ integrity and function and
      regulate the innate inflammatory response within the gland.

PMID- 22156513
TI  - Multiple layers of CD80/86-dependent costimulatory activity regulate primary,
      memory, and secondary lymphocytic choriomeningitis virus-specific T cell
      immunity.
AB  - The lymphocytic choriomeningitis virus (LCMV) system constitutes one of the most
      widely used models for the study of infectious disease and the regulation of
      virus-specific T cell immunity. However, with respect to the activity of
      costimulatory and associated regulatory pathways, LCMV-specific T cell responses
      have long been regarded as relatively independent and thus distinct from the
      regulation of T cell immunity directed against many other viral pathogens. Here,
      we have reevaluated the contribution of CD28-CD80/86 costimulation in the LCMV
      system by use of CD80/86-deficient mice, and our results demonstrate that a
      disruption of CD28-CD80/86 signaling compromises the magnitude, phenotype, and/or
      functionality of LCMV-specific CD8(+) and/or CD4(+) T cell populations in all
      stages of the T cell response. Notably, a profound inhibition of secondary T cell
      immunity in LCMV-immune CD80/86-deficient mice emerged as a composite of both
      defective memory T cell development and a specific requirement for CD80 but not
      CD86 in the recall response, while a related experimental scenario of CD28
      dependent yet CD80/86-independent secondary CD8(+) T cell immunity suggests the
      existence of a CD28 ligand other than CD80/86. Furthermore, we provide evidence
      that regulatory T cells (T(REG)s), the homeostasis of which is altered in
      CD80/86(-/-) mice, contribute to restrained LCMV-specific CD8(+) T cell responses
      in the presence of CD80/86. Our observations can therefore provide a more
      coherent perspective on CD28-CD80/86 costimulation in antiviral T cell immunity
      that positions the LCMV system within a shared context of multiple defects that
      virus-specific T cells acquire in the absence of CD28-CD80/86 costimulation.

PMID- 22156515
TI  - Identification of adenovirus serotype 5 hexon regions that interact with
      scavenger receptors.
AB  - Most of an intravenous dose of species C adenovirus serotype 5 (Ad5) is destroyed
      by liver Kupffer cells. In contrast, another species C virus, Ad6, evades these
      cells to mediate more efficient liver gene delivery. Given that this difference
      in Kupffer cell interaction is mediated by the hypervariable (HVR) loops of the
      virus hexon protein, we genetically modified each of the seven HVRs of Ad5 with a
      cysteine residue to enable conditional blocking of these sites with polyethylene
      glycol (PEG). We show that these modifications do not affect in vitro virus
      transduction. In contrast, after intravenous injection, targeted PEGylation at
      HVRs 1, 2, 5, and 7 increased viral liver transduction up to 20-fold. Elimination
      or saturation of liver Kupffer cells did not significantly affect this increase
      in the liver transduction. In vitro, PEGylation blocked uptake of viruses via the
      Kupffer cell scavenger receptor SRA-II. These data suggest that HVRs 1, 2, 5, and
      7 of Ad5 may be involved in Kupffer cell recognition and subsequent destruction.
      These data also demonstrate that this conditional genetic-chemical mutation
      strategy is a useful tool for investigating the interactions of viruses with host
      tissues.

PMID- 22156516
TI  - Human cytomegalovirus UL44 concentrates at the periphery of replication
      compartments, the site of viral DNA synthesis.
AB  - The formation of replication compartments, the subnuclear structures in which the
      viral DNA genome is replicated, is a hallmark of herpesvirus infections. The
      localization of proteins and viral DNA within human cytomegalovirus replication
      compartments is not well characterized. Immunofluorescence analysis demonstrated
      the accumulation of the viral DNA polymerase subunit UL44 at the periphery of
      replication compartments and the presence of different populations of UL44 in
      infected cells. In contrast, the viral single-stranded-DNA binding protein UL57
      was distributed throughout replication compartments. Using "click chemistry" to
      detect 5-ethynyl-2'-deoxyuridine (EdU) incorporation into replicating viral DNA
      and pulse-chase protocols, we found that viral DNA synthesis occurs at the
      periphery of replication compartments and that replicated viral DNA subsequently
      localizes to the interior of replication compartments. The interiors of
      replication compartments also contain regions in which UL44 and EdU-labeled DNA
      are absent. The treatment of cells with a viral DNA polymerase inhibitor
      reversibly caused the dispersal of both UL44 and EdU-labeled viral DNA from
      replication compartments, indicating that ongoing viral DNA synthesis is
      necessary to maintain the organization of replication compartments. Our results
      reveal a previously unappreciated complexity of the organization of human
      cytomegalovirus replication compartments.

PMID- 22156517
TI  - A highly conserved residue in the C-terminal helix of HIV-1 matrix is required
      for envelope incorporation into virus particles.
AB  - The incorporation of viral envelope (Env) glycoproteins into nascent particles is
      an essential step in the production of infectious human immunodeficiency virus
      type 1 (HIV-1). This process has been shown to require interactions between Env
      and the matrix (MA) domain of the Gag polyprotein. Previous studies indicate that
      several residues in the N-terminal region of MA are required for Env
      incorporation. However, the precise mechanism by which Env proteins are acquired
      during virus assembly has yet to be fully defined. Here, we examine whether a
      highly conserved glutamate at position 99 in the C-terminal helix is required for
      MA function and HIV-1 replication. We analyze a panel of mutant viruses that
      contain different amino acid substitutions at this position using viral
      infectivity studies, virus-cell fusion assays, and immunoblotting. We find that
      E99V mutant viruses are defective for fusion with cell membranes and thus are
      noninfectious. We show that E99V mutant particles of HIV-1 strains LAI and NL4.3
      lack wild-type levels of Env proteins. We identify a compensatory substitution in
      MA residue 84 and show that it can reverse the E99V-associated defects. Taken
      together, these results indicate that the C-terminal hydrophobic pocket of MA,
      which encompasses both residues 84 and 99, has a previously unsuspected and key
      role in HIV-1 Env incorporation.

PMID- 22156518
TI  - Enhancement of hepatitis B virus replication by androgen and its receptor in
      mice.
AB  - Hepatitis B virus (HBV) is an important pathogen that chronically infects more
      men than women. To understand the molecular mechanism of this gender disparity,
      we analyzed HBV replication in transgenic mice that carried the HBV genome with
      or without the ability to express the HBV X protein (HBx). We found that gender
      had no effect on HBV surface antigen (HBsAg), DNA, and RNA levels in mice before
      puberty, but its effect on HBV after puberty was apparent, with HBV replicating
      approximately twice more efficiently in male mice than in female mice whether or
      not HBx was expressed. The castration of male mice resulted in a reduction of HBV
      HBsAg, DNA, and RNA levels, which could be partially restored by the injection of
      the androgen agonist R1881, indicating a positive role of androgen in HBV
      replication. The introduction of HBV genomic DNA and androgen receptor (AR) short
      hairpin RNA (shRNA) into the liver of naive mice by hydrodynamic injection
      revealed that the effect of androgen on HBV was dependent on its receptor, which
      apparently could also stimulate HBV replication via an androgen-independent
      pathway. Further studies indicated that the two previously identified androgen
      response elements (AREs) in the HBV genome could indeed mediate the effect of
      androgen on HBV RNA transcription and DNA replication in vivo. These effects of
      androgen and its receptor on HBV thus provide an explanation for why men have a
      higher risk of HBV infection than women.

PMID- 22156519
TI  - Low-dose penile SIVmac251 exposure of rhesus macaques infected with adenovirus
      type 5 (Ad5) and then immunized with a replication-defective Ad5-based SIV
      gag/pol/nef vaccine recapitulates the results of the phase IIb step trial of a
      similar HIV-1 vaccine.
AB  - The Step Trial showed that the MRKAd5 HIV-1 subtype B Gag/Pol/Nef vaccine did not
      protect men from HIV infection or reduce setpoint plasma viral RNA (vRNA) levels
      but, unexpectedly, it did modestly enhance susceptibility to HIV infection in
      adenovirus type 5 (Ad5)-seropositive, uncircumcised men. As part of the process
      to understand the results of the Step Trial, we designed a study to determine
      whether rhesus macaques chronically infected with a host-range mutant Ad5 (Ad5hr)
      and then immunized with a replication defective Ad5 SIVmac239 Gag/Pol/Nef vaccine
      were more resistant or susceptible to SIV infection than unimmunized rhesus
      macaques challenged with a series of escalating dose penile exposures to SIVmac
      251. The Ad5 SIV vaccine induced CD8(+) T cell responses in 70% of the monkeys,
      which is similar to the proportion of humans that responded to the vaccine in the
      Step Trial. However, the vaccine did not protect vaccinated animals from penile
      SIV challenge. At the lowest SIV exposure dose (10(3) 50% tissue culture
      infective doses), 2 of 9 Ad5-seropositive animals immunized with the Ad5 SIV
      vaccine became infected compared to 0 of 34 animals infected in the other animal
      groups (naive animals, Ad5-seropositive animals immunized with the empty Ad5
      vector, Ad5-seronegative animals immunized with the Ad5 SIV vaccine, and Ad5
      seronegative animals immunized with the empty Ad5 vector). Penile exposure to
      more concentrated virus inocula produced similar rates of infection in all animal
      groups. Although setpoint viral loads were unaffected in Step vaccinees, the Ad5
      SIV-immunized animals had significantly lower acute-phase plasma vRNA levels
      compared to unimmunized animals. Thus, the results of the nonhuman primate (NHP)
      study described here recapitulate the lack of protection against HIV acquisition
      seen in the Step Trial and suggest a greater risk of infection in the Ad5
      seropositive animals immunized with the Ad5 SIV vaccine. Further studies are
      necessary to confirm the enhancement of virus acquisition and to discern
      associated mechanisms.

PMID- 22156520
TI  - Structural determinants for nuclear envelope localization and function of
      pseudorabies virus pUL34.
AB  - Herpesvirus proteins pUL34 and pUL31 form a complex at the inner nuclear membrane
      (INM) which is necessary for efficient nuclear egress. Pseudorabies virus (PrV)
      pUL34 is a type II membrane protein of 262 amino acids (aa). The transmembrane
      region (TM) is predicted to be located between aa 245 and 261, leaving only one
      amino acid in the C terminus that probably extends into the perinuclear space. It
      is targeted to the nuclear envelope in the absence of other viral proteins,
      pointing to intrinsic localization motifs, and shows structural similarity to
      cellular INM proteins like lamina-associated polypeptide (Lap) 2beta and Emerin.
      To investigate which domains of pUL34 are relevant for localization and function,
      we constructed chimeric proteins by replacing parts of pUL34 with regions of
      cellular INM proteins. First the 18 C-terminal amino acids encompassing the TM
      were exchanged with TM regions and C-terminal domains of Lap2beta and Emerin or
      with the first TM region of the polytopic lamin B receptor (LBR), including the
      nine following amino acids. All resulting chimeric proteins complemented the
      replication defect of PrV-DeltaUL34, demonstrating that the substitution of the
      TM and the extension of the C-terminal domain does not interfere with the
      function of pUL34. Complementation was reduced but not abolished when the C
      terminal 50 aa were replaced by corresponding Lap2beta sequences (pUL34-LapCT50).
      However, replacing the C-terminal 100 aa (pUL34-LapCT100) resulted in a
      nonfunctional protein despite continuing pUL31 binding, pointing to an important
      functional role of this region. The replacement of the N-terminal 100 aa (pUL34
      LapNT100) had no effect on nuclear envelope localization but abrogated pUL31
      binding and function.

PMID- 22156521
TI  - A single-amino-acid polymorphism in reovirus protein MU2 determines repression of
      interferon signaling and modulates myocarditis.
AB  - Myocarditis is indicated as the second leading cause of sudden death in young
      adults. Reovirus induces myocarditis in neonatal mice, providing a tractable
      model system for investigation of this important disease. Alpha/beta-interferon
      (IFN-alpha/beta) treatment improves cardiac function and inhibits viral
      replication in patients with chronic myocarditis, and the host IFN-alpha/beta
      response is a determinant of reovirus strain-specific differences in induction of
      myocarditis. Virus-induced IFN-beta stimulates a signaling cascade that
      establishes an antiviral state and further induces IFN-alpha/beta through an
      amplification loop. Reovirus strain-specific differences in induction of and
      sensitivity to IFN-alpha/beta are associated with the viral M1, L2, and S2 genes.
      The reovirus M1 gene-encoded MU2 protein is a strain-specific repressor of IFN
      beta signaling, providing one possible mechanism for the variation in resistance
      to IFN and induction of myocarditis between different reovirus strains. We report
      here that MU2 amino acid 208 determines repression of IFN-beta signaling and
      modulates reovirus induction of IFN-beta in cardiac myocytes. Moreover, MU2 amino
      acid 208 determines reovirus replication, both in initially infected cardiac
      myocytes and after viral spread, by regulating the IFN-beta response. Amino acid
      208 of MU2 also influences the cytopathic effect in cardiac myocytes after
      spread. Finally, MU2 amino acid 208 modulates myocarditis in neonatal mice. Thus,
      repression of IFN-beta signaling mediated by reovirus MU2 amino acid 208 is a
      determinant of the IFN-beta response, viral replication and damage in cardiac
      myocytes, and myocarditis. These results demonstrate that a single amino acid
      difference between viruses can dictate virus strain-specific differences in
      suppression of the host IFN-beta response and, consequently, damage to the heart.

PMID- 22156522
TI  - Longitudinal analysis of early HIV-1-specific neutralizing activity in an elite
      neutralizer and in five patients who developed cross-reactive neutralizing
      activity.
AB  - We previously established that at 3 years postseroconversion, ~30% of HIV
      infected individuals have cross-reactive neutralizing activity (CrNA) in their
      sera. Here we studied the kinetics with which CrNA develops and how these relate
      to the development of autologous neutralizing activity as well as viral escape
      and diversification. For this purpose, sera from five individuals with CrNA and
      one elite neutralizer that were obtained at three monthly intervals in the first
      year after seroconversion and at multiple intervals over the disease course were
      tested for neutralizing activity against an established multiclade panel of six
      viruses. The same serum samples, as well as sera from three individuals who
      lacked CrNA, were tested for their neutralizing activities against autologous
      clonal HIV-1 variants from multiple time points covering the disease course from
      seroconversion onward. The elite neutralizer already had CrNA at 9.8 months
      postseroconversion, in contrast with the findings for the other five patients, in
      whom CrNA was first detected at 20 to 35 months postseroconversion and peaked
      around 35 months postseroconversion. In all patients, CrNA coincided with
      neutralizing activity against autologous viruses that were isolated <12 months
      postseroconversion, while viruses from later time points had already escaped
      autologous neutralizing activity. Also, the peak in gp160 sequence diversity
      coincided with the peak of CrNA titers. Individuals who lacked CrNA had lower
      peak autologous neutralizing titers, viral escape, and sequence diversity than
      individuals with CrNA. A better understanding of the underlying factors that
      determine the presence of CrNA or even an elite neutralizer phenotype may aid in
      the design of an HIV-1 vaccine.

PMID- 22156523
TI  - Crystal structure of the Japanese encephalitis virus envelope protein.
AB  - Japanese encephalitis virus (JEV) is the leading global cause of viral
      encephalitis. The JEV envelope protein (E) facilitates cellular attachment and
      membrane fusion and is the primary target of neutralizing antibodies. We have
      determined the 2.1-A resolution crystal structure of the JEV E ectodomain
      refolded from bacterial inclusion bodies. The E protein possesses the three
      domains characteristic of flavivirus envelopes and epitope mapping of
      neutralizing antibodies onto the structure reveals determinants that correspond
      to the domain I lateral ridge, fusion loop, domain III lateral ridge, and domain
      I-II hinge. While monomeric in solution, JEV E assembles as an antiparallel dimer
      in the crystal lattice organized in a highly similar fashion as seen in cryo
      electron microscopy models of mature flavivirus virions. The dimer interface,
      however, is remarkably small and lacks many of the domain II contacts observed in
      other flavivirus E homodimers. In addition, uniquely conserved histidines within
      the JEV serocomplex suggest that pH-mediated structural transitions may be aided
      by lateral interactions outside the dimer interface in the icosahedral virion.
      Our results suggest that variation in dimer structure and stability may
      significantly influence the assembly, receptor interaction, and uncoating of
      virions.

PMID- 22156524
TI  - Identification of cell surface molecules involved in dystroglycan-independent
      Lassa virus cell entry.
AB  - Although O-mannosylated dystroglycan is a receptor for Lassa virus, a causative
      agent of Lassa fever, recent findings suggest the existence of an alternative
      receptor(s). Here we identified four molecules as receptors for Lassa virus: Axl
      and Tyro3, from the TAM family, and dendritic cell-specific intercellular
      adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver and lymph node
      sinusoidal endothelial calcium-dependent lectin (LSECtin), from the C-type lectin
      family. These molecules enhanced the binding of Lassa virus to cells and mediated
      infection independently of dystroglycan. Axl- or Tyro3-mediated infection
      required intracellular signaling via the tyrosine kinase activity of Axl or
      Tyro3, whereas DC-SIGN- or LSECtin-mediated infection and binding were dependent
      on a specific carbohydrate and on ions. The identification of these four
      molecules as Lassa virus receptors advances our understanding of Lassa virus cell
      entry.

PMID- 22156525
TI  - High-mannose glycan-dependent epitopes are frequently targeted in broad
      neutralizing antibody responses during human immunodeficiency virus type 1
      infection.
AB  - Broad and potent neutralizing antibody (BNAb) responses are rare in people
      infected by human immunodeficiency virus type 1 (HIV-1). Clearly defining the
      nature of BNAb epitopes on HIV-1 envelope glycoproteins (Envs) targeted in vivo
      is critical for future directions of anti-HIV-1 vaccine development. Conventional
      techniques are successful in defining neutralizing epitopes in a small number of
      individual subjects but fail in studying large groups of subjects. Two
      independent methods were employed to investigate the nature of NAb epitopes
      targeted in 9 subjects, identified by the NIAID Center for HIV/AIDS Vaccine
      Immunology (CHAVI) 001 and 008 clinical teams, known to make a strong BNAb
      response. Neutralizing activity from 8/9 subjects was enhanced by enriching high
      mannose N-linked glycan (HM-glycan) of HIV-1 glycoproteins on neutralization
      target viruses and was sensitive to specific glycan deletion mutations of HIV-1
      glycoproteins, indicating that HM-glycan-dependent epitopes are targeted by BNAb
      responses in these subjects. This discovery adds to accumulating evidence
      supporting the hypothesis that glycans are important targets on HIV-1
      glycoproteins for BNAb responses in vivo, providing an important lead for future
      directions in developing NAb-based anti-HIV-1 vaccines.

PMID- 22156526
TI  - Viral interferon regulatory factors decrease the induction of type I and type II
      interferon during rhesus macaque rhadinovirus infection.
AB  - Kaposi's sarcoma-associated herpesvirus and rhesus macaque rhadinovirus (RRV),
      two closely related gammaherpesviruses, are unique in their expression of viral
      homologs of cellular interferon regulatory factors (IRFs), termed viral IRFs
      (vIRFs). To assess the role of vIRFs during de novo infection, we have utilized
      the bacterial artificial chromosome clone of wild-type RRV(17577) (WT(BAC) RRV)
      to generate a recombinant virus with all 8 of the vIRFs deleted (vIRF-ko RRV).
      The infection of primary rhesus fibroblasts and peripheral blood mononuclear
      cells (PBMCs) with vIRF-ko RRV resulted in earlier and increased induction of
      type I interferon (IFN) (IFN-alpha/beta) and type II IFN (IFN-gamma).
      Additionally, plasmacytoid dendritic cells maintained higher levels of IFN-alpha
      production in PBMC cultures infected with vIRF-ko RRV than in cultures infected
      with WT(BAC) RRV. Moreover, the nuclear accumulation of phosphorylated IRF-3,
      which is necessary for the induction of type I IFN, was also inhibited following
      WT(BAC) RRV infection. These findings demonstrate that during de novo RRV
      infection, vIRFs are inhibiting the induction of IFN at the transcriptional
      level, and one potential mechanism for this is the disruption of the activation
      and localization of IRF-3.

PMID- 22156527
TI  - Role of beta-catenin and TCF/LEF family members in transcriptional activity of
      HIV in astrocytes.
AB  - The Wnt/beta-catenin pathway is involved in diverse cell functions governing
      development and disease. beta-Catenin, a central mediator of this pathway, binds
      to members of the TCF/LEF family of transcription factors to modulate hundreds of
      genes. Active Wnt/beta-catenin/TCF-4 signaling plays a significant role in
      repression of HIV-1 replication in multiple cell targets, including astrocytes.
      To determine the mechanism by which active beta-catenin/TCF-4 leads to inhibition
      of HIV replication, we knocked down beta-catenin or TCF/LEF members in primary
      astrocytes and astrocytomas transiently transfected with an HIV long terminal
      repeat (LTR)-luciferase reporter that contained an integrated copy of the HIV LTR
      luciferase construct. Knockdown of either beta-catenin or TCF-4 induced LTR
      activity by 2- to 3-fold under both the episomal and integrated conditions. This
      knockdown also increased presence of serine 2-phosphorylated RNA polymerase II
      (Pol II) on the HIV LTR as well as enhanced its processivity. Knockdown of beta
      catenin/TCF-4 also impacted tethering of other transcription factors on the HIV
      promoter. Specifically, knockdown of TCF-4 enhanced binding of C/EBPbeta,
      C/EBPdelta, and NF-kappaB to the HIV LTR, while beta-catenin knockdown increased
      binding of C/EBPbeta and C/EBPdelta but had no effect on NF-kappaB. Approximately
      150 genes in astrocytes were impacted by beta-catenin knockdown, including genes
      involved in inflammation/immunity, uptake/transport, vesicular
      transport/exocytosis, apoptosis/cellular stress, and cytoskeleton/trafficking.
      These findings indicate that modulation of the beta-catenin/TCF-4 axis impacts
      the basal level of HIV transcription in astrocytes, which may drive low
      level/persistent HIV in astrocytes that can contribute to ongoing
      neuroinflammation, and this axis also has profound effects on astrocyte biology.

PMID- 22156528
TI  - Selection and accumulation of an HIV-1 escape mutant by three types of HIV-1
      specific cytotoxic T lymphocytes recognizing wild-type and/or escape mutant
      epitopes.
AB  - It is known that cytotoxic T lymphocytes (CTLs) recognizing HIV-1 escape mutants
      are elicited in HIV-1-infected individuals, but their role in the control of HIV
      1 replication remains unclear. We investigated the antiviral ability of CTLs
      recognizing the HLA-A*24:02-restricted Gag28 -36 (KYKLKHIVW) epitope and/or its
      escape mutant (KYRLKHIVW) elicited in the early and chronic phases of the
      infection. Wild-type (WT)-epitope-specific CTLs, as well as cross-reactive CTLs
      recognizing both WT and K30R (3R) epitopes, which were predominantly elicited at
      early and/or chronic phases in HLA-A*24:02(+) individuals infected with the WT
      virus, suppressed the replication of the WT virus but failed to suppress that of
      the 3R virus, indicating that the 3R virus was selected by these 2 types of CTLs.
      On the other hand, cross-reactive and 3R-specific CTLs, which were elicited in
      those infected with the 3R virus, did not suppress the replication of either WT
      or 3R virus, indicating that these CTLs did not contribute to the control of 3R
      virus replication. High accumulation of the 3R mutation was found in a Japanese
      population recently recruited. The selection and accumulation of this 3R mutation
      resulted from the antiviral ability of these Gag28-specific CTLs and high
      prevalence of HLA-A*24:02 in a Japanese population. The present study highlighted
      the mechanisms for the roles of cross-reactive and mutant-epitope-specific CTLs,
      as well as high accumulation of escape mutants, in an HIV-1-infected population.

PMID- 22156529
TI  - The Andes hantavirus NSs protein is expressed from the viral small mRNA by a
      leaky scanning mechanism.
AB  - The small mRNA (SmRNA) of all Bunyaviridae encodes the nucleocapsid (N) protein.
      In 4 out of 5 genera in the Bunyaviridae, the smRNA encodes an additional
      nonstructural protein denominated NSs. In this study, we show that Andes
      hantavirus (ANDV) SmRNA encodes an NSs protein. Data show that the NSs protein is
      expressed in the context of an ANDV infection. Additionally, our results suggest
      that translation initiation from the NSs initiation codon is mediated by
      ribosomal subunits that have bypassed the upstream N protein initiation codon
      through a leaky scanning mechanism.

PMID- 22156530
TI  - Development of a novel nonhuman primate model for Rift Valley fever.
AB  - Rift Valley fever (RVF) virus (RVFV) can cause severe human disease characterized
      by either acute-onset hepatitis, delayed-onset encephalitis, retinitis and
      blindness, or a hemorrhagic syndrome. The existing nonhuman primate (NHP) model
      for RVF utilizes an intravenous (i.v.) exposure route in rhesus macaques (Macaca
      mulatta). Severe disease in these animals is infrequent, and large cohorts are
      needed to observe significant morbidity and mortality. To overcome these
      drawbacks, we evaluated the infectivity and pathogenicity of RVFV in the common
      marmoset (Callithrix jacchus) by i.v., subcutaneous (s.c.), and intranasal
      exposure routes to more closely mimic natural exposure. Marmosets were more
      susceptible to RVFV than rhesus macaques and experienced higher rates of
      morbidity, mortality, and viremia and marked aberrations in hematological and
      chemistry values. An overwhelming infection of hepatocytes was a major
      consequence of infection of marmosets by the i.v. and s.c. exposure routes.
      Additionally, these animals displayed signs of hemorrhagic manifestations and
      neurological impairment. Based on our results, the common marmoset model more
      closely resembles severe human RVF disease and is therefore an ideal model for
      the evaluation of potential vaccines and therapeutics.

PMID- 22156531
TI  - Formation of higher-order foot-and-mouth disease virus 3D(pol) complexes is
      dependent on elongation activity.
AB  - The replication of many viruses involves the formation of higher-order structures
      or replication "factories." We show that the key replication enzyme of foot-and
      mouth disease virus (FMDV), the RNA-dependent RNA polymerase, forms fibrils in
      vitro. Although there are similarities with previously characterized poliovirus
      polymerase fibrils, FMDV fibrils are narrower, are composed of both protein and
      RNA, and, importantly, are seen only when all components of an elongation assay
      are present. Furthermore, an inhibitory RNA aptamer prevents fibril formation.

PMID- 22156532
TI  - Production of infectious chimeric hepatitis C virus genotype 2b harboring minimal
      regions of JFH-1.
AB  - To establish a cell culture system for chimeric hepatitis C virus (HCV) genotype
      2b, we prepared a chimeric construct harboring the 5' untranslated region (UTR)
      to the E2 region of the MA strain (genotype 2b) and the region of p7 to the 3'
      UTR of the JFH-1 strain (genotype 2a). This chimeric RNA (MA/JFH-1.1) replicated
      and produced infectious virus in Huh7.5.1 cells. Replacement of the 5' UTR of
      this chimera with that from JFH-1 (MA/JFH-1.2) enhanced virus production, but
      infectivity remained low. In a long-term follow-up study, we identified a cell
      culture-adaptive mutation in the core region (R167G) and found that it enhanced
      virus assembly. We previously reported that the NS3 helicase (N3H) and the region
      of NS5B to 3' X (N5BX) of JFH-1 enabled replication of the J6CF strain (genotype
      2a), which could not replicate in cells. To reduce JFH-1 content in MA/JFH-1.2,
      we produced a chimeric viral genome for MA harboring the N3H and N5BX regions of
      JFH-1, combined with a JFH-1 5' UTR replacement and the R167G mutation
      (MA/N3H+N5BX-JFH1/R167G). This chimeric RNA replicated efficiently, but virus
      production was low. After the introduction of four additional cell culture
      adaptive mutations, MA/N3H+N5BX-JFH1/5am produced infectious virus efficiently.
      Using this chimeric virus harboring minimal regions of JFH-1, we analyzed
      interferon sensitivity and found that this chimeric virus was more sensitive to
      interferon than JFH-1 and another chimeric virus containing more regions from JFH
      1 (MA/JFH-1.2/R167G). In conclusion, we established an HCV genotype 2b cell
      culture system using a chimeric genome harboring minimal regions of JFH-1. This
      cell culture system may be useful for characterizing genotype 2b viruses and
      developing antiviral strategies.

PMID- 22156533
TI  - The NK cell response to mouse cytomegalovirus infection affects the level and
      kinetics of the early CD8(+) T-cell response.
AB  - Natural killer (NK) cells and CD8(+) T cells play a prominent role in the
      clearance of mouse cytomegalovirus (MCMV) infection. The role of NK cells in
      modulating the CD8(+) T-cell response to MCMV infection is still the subject of
      intensive research. For analyzing the impact of NK cells on mounting of a CD8(+)
      T-cell response and the contribution of these cells to virus control during the
      first days postinfection (p.i.), we used C57BL/6 mice in which NK cells are
      specifically activated through the Ly49H receptor engaged by the MCMV-encoded
      ligand m157. Our results indicate that the requirement for CD8(+) T cells in
      early MCMV control inversely correlates with the engagement of Ly49H. While
      depletion of CD8(+) T cells has only a minor effect on the early control of wild
      type MCMV, CD8(+) T cells are essential in the control of Deltam157 virus. The
      frequencies of virus epitope-specific CD8(+) T cells and their activation status
      were higher in mice infected with Deltam157 virus. In addition, these mice showed
      elevated levels of alpha interferon (IFN-alpha) and several other proinflammatory
      cytokines as early as 1.5 days p.i. Although the numbers of conventional
      dendritic cells (cDCs) were reduced later during infection, particularly in
      Deltam157-infected mice, they were not significantly affected at the peak of the
      cytokine response. Altogether, we concluded that increased antigen load,
      preservation of early cDCs' function, and higher levels of innate cytokines
      collectively account for an enhanced CD8(+) T-cell response in C57BL/6 mice
      infected with a virus unable to activate NK cells via the Ly49H-m157 interaction.

PMID- 22156534
TI  - Conformational changes in Sindbis virus induced by decreased pH are revealed by
      small-angle neutron scattering.
AB  - Alphaviruses, such as Sindbis virus, undergo dramatic changes in three
      dimensional structure upon exposure to low pH, and such exposure can establish
      conditions allowing fusion of the virus membrane with a cell plasma membrane upon
      return to neutral pH. While exposure to low pH is not required for entry of
      Sindbis virus into vertebrate or invertebrate cells, the conformational changes
      occurring at low pH may mimic those occurring upon virus-receptor interaction.
      Here, we employed small-angle neutron scattering with contrast variation to probe
      how the structure of a mammalian-grown Sindbis virus responds to moderately
      acidic pH. Several changes took place throughout the virion structure when the pH
      decreased from 7.2 to 6.4. Specifically, the RNA in the virion core underwent a
      conformational change. Additionally, the protein was redistributed. A significant
      amount of protein moved from the layer containing the lipid bilayer to the
      exterior of the virion. The results improve our understanding of the pH-driven
      alteration of Sindbis virus structure.

PMID- 22156535
TI  - Evolution of poliovirus defective interfering particles expressing Gaussia
      luciferase.
AB  - Polioviruses (PVs) carrying a reporter gene are useful tools for studies of virus
      replication, particularly if the viral chimeras contain the polyprotein that
      provides all of the proteins necessary for a complete replication cycle.
      Replication in HeLa cells of a previously constructed poliovirus expressing the
      gene for Renilla luciferase (RLuc) fused to the N terminus of the polyprotein
      H(2)N-RLuc-P1-P2-P3-COOH (P1, structural domain; P2 and P3, nonstructural
      domains) led to the deletion of RLuc after only one passage. Here we describe a
      novel poliovirus chimera that expresses Gaussia luciferase (GLuc) inserted into
      the polyprotein between P1 and P2 (N(2)H-P1-GLuc-P2-P3-COOH). This chimera,
      termed PV-GLuc, replicated to 10% of wild-type yield. The reporter signal was
      fully retained for three passages and then gradually lost. After six passages the
      signal was barely detectable. On further passages, however, the GLuc signal
      reappeared, and after eight passages it had reached the same levels observed with
      the original PV-GLuc at the first passage. We demonstrated that this surprising
      observation was due to coevolution of defective interfering (DI) particles that
      had lost part or all of the capsid coding sequence (DeltaP1-GLuc-P2-P3) and wild
      type-like viruses that had lost the GLuc sequence (P1-P2-P3). When used at low
      passage, PV-GLuc is an excellent tool for studying aspects of genome replication
      and morphogenesis. The GLuc protein was secreted from mammalian cells but, in
      agreement with published data, was not secreted from PV-GLuc-infected cells due
      to poliovirus-induced inhibition of cellular protein secretion. Published
      evidence indicates that individual expression of enterovirus polypeptide 3A, 2B,
      or 2BC in COS-1 cells strongly inhibits host protein secretion. In HeLa cells,
      however, expression of none of the poliovirus polypeptides, either singly or in
      pairs, inhibited GLuc secretion. Thus, inhibition of GLuc secretion in PV
      infected HeLa cells is likely a result of the interaction between several viral
      and cellular proteins that are different from those in COS-1 cells.

PMID- 22156536
TI  - Prionemia and leukocyte-platelet-associated infectivity in sheep transmissible
      spongiform encephalopathy models.
AB  - The dynamics of the circulation and distribution of transmissible spongiform
      encephalopathy (TSE) agents in the blood of infected individuals remain largely
      unknown. This clearly limits the understanding of the role of blood in TSE
      pathogenesis and the development of a reliable TSE blood detection assay. Using
      two distinct sheep scrapie models and blood transfusion, this work demonstrates
      the occurrence of a very early and persistent prionemia. This ability to transmit
      disease by blood transfusion was correlated with the presence of infectivity in
      white blood cells (WBC) and peripheral blood mononucleated cells (PBMC) as
      detected by bioassay in mice overexpressing the ovine prion protein PrP (tg338
      mice) and with the identification of abnormal PrP in WBC after using protein
      misfolding cyclic amplification (PMCA). Platelets and a large variety of
      leukocyte subpopulations also were shown to be infectious. The use of endpoint
      titration in tg338 mice indicated that the infectivity in WBC (per ml of blood)
      was 10(6.5)-fold lower than that in 1 g of posterior brainstem sample. In both
      WBC and brainstem, infectivity displayed similar resistance to PK digestion. The
      data strongly support the concept that WBC are an accurate target for reliable
      TSE detection by PMCA. The presence of infectivity in short-life-span blood
      cellular elements raises the question of the origin of prionemia.

PMID- 22156537
TI  - Mitochondrial metabolic control of microtubule dynamics impairs the autophagic
      pathway in Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder
      where the loss of dopaminergic neurons in the substantia nigra and the presence
      of Lewy bodies in surviving neurons are primary histopathological hallmarks.
      Recent evidence points to mitochondrial dysfunction as a common upstream event in
      PD etiopathology. OBJECTIVE: In this overview, we will discuss some of our
      findings that provide support for the mitochondrial cascade hypothesis, whereas
      mitochondrial deficits trigger PD pathology through alterations in microtubule
      integrity and macroautophagy. METHODS: Using, as a PD model, cells that have PD
      patients' mitochondrial DNA, cells without mitochondrial DNA and MPP(+)-treated
      cells, we showed that mitochondrial metabolism alteration may underlie changes in
      the microtubular net and in the autophagic-lysosomal pathway. CONCLUSIONS:
      Finally, we will endow a potential new therapeutic target for PD pathology.

PMID- 22156538
TI  - Yolk sac diameter in early pregnancy in maternal diabetes mellitus.
AB  - AIMS: To investigate the possible association between maternal diabetes mellitus
      and increased yolk sac diameter (YSD). METHODS: We searched the Early Pregnancy
      Unit database to identify singleton pregnancies with measurements of embryonic
      crown-rump length (CRL) and YSD at 6-10 weeks of gestation and subsequent
      delivery of phenotypically normal neonates. We compared the YSD in patients with
      pre-gestational and gestational diabetes with those who were unaffected by
      diabetes. RESULTS: A total of 3,686 cases were identified including 43 (1.2%)
      with type 1 diabetes, 31 (0.8%) with type 2 diabetes and 71 (1.9%) who
      subsequently developed gestational diabetes. The measured YSD in both the
      diabetic and non-diabetic groups were expressed as differences from the expected
      normal mean for CRL (Delta values). There were no significant differences in
      DeltaYSD between the groups. The median (IQR) DeltaYSD was 0.01 (-0.33 to 0.37)
      mm in the unaffected group, 0.01 (-0.35 to 0.51) mm in type 1 diabetes, -0.02 (
      3.44 to 0.27) mm in type 2 diabetes and 0.01 (-0.28 to 0.35) mm in gestational
      diabetes. CONCLUSION: After exclusion of miscarriages and embryopathies, pre
      gestational and gestational diabetes are not associated with altered YSD.

PMID- 22156539
TI  - Disease characteristics in non-erosive reflux disease with and without
      endoscopically minimal change esophagitis: are they different?
AB  - BACKGROUND/AIMS: The majority of patients with gastroesophageal reflux disease
      (GERD) appear to have non-erosive reflux disease (NERD). NERD may include minimal
      change esophagitis (MCE) and no endoscopic abnormalities (MCE-). We aimed to
      determine whether intraesophageal acid reflux as well as esophageal motility
      differed between patients with and without MCE. METHODS: Consecutive patients
      with classic reflux symptoms were enrolled in the study. Patients without any
      mucosal injury were considered to be MCE-. Esophageal acid exposure as well as
      intragastric pH (<4) was determined by dual-channel ambulatory 24-hour pH
      monitoring. RESULTS: A total of 100 patients (MCE-, 52 patients; MCE, 48
      patients) were studied. The percentage of effective peristalsis was found similar
      between patients with and without MCE (p = NS). Esophageal acid contact as well
      as the DeMeester score did not differ between the groups (p = NS). The prevalence
      of positive symptom index was greater in MCE- patients than in MCE patients (p =
      0.001). Intragastric acidity (pH <4) was similar between MCE- and MCE groups (p =
      NS). CONCLUSIONS: NERD, regardless of the presence of MCE, might exhibit similar
      disease characteristics in terms of esophageal acid exposure and motor
      dysfunction.

PMID- 22156540
TI  - The genetics of 3-M syndrome: unravelling a potential new regulatory growth
      pathway.
AB  - 3-M syndrome is an autosomal recessive primordial growth disorder characterised
      by severe postnatal growth restriction caused by mutations in CUL7, OBSL1 or
      CCDC8. Clinical characteristics include dysmorphic facial features and fleshy
      prominent heels with a variable degree of radiological abnormalities. CUL7 is a
      structural protein central to the formation of an ubiquitin E3 ligase that is
      known to target insulin receptor substrate 1 for degradation. CUL7 also binds to
      p53 and may be involved in the control of p53-dependent apoptosis. OBSL1 is a
      cytoskeletal adaptor protein that was thought to play a central role in myocyte
      remodelling, and CCDC8 has no defined function as yet. However, the physical
      interaction of OBSL1 with both CUL7 and CCDC8 and its potential role in the
      regulation of CUL7 expression suggest all three proteins are members of the same
      growth-regulatory pathway. Future work should be directed to investigating the
      function of the 3-M syndrome pathway and in particular the role in the insulin
      like growth factor I signalling pathway with a view of potentially revealing new
      therapeutic targets and identifying key regulators of cellular growth.

PMID- 22156541
TI  - Impact of age and duration of growth hormone therapy in children with Turner
      syndrome.
AB  - BACKGROUND/AIMS: To assess height standard deviation scores (HSDS) in patients
      with Turner syndrome (TS) by age at treatment initiation and varying durations of
      treatment with growth hormone (GH). METHODS: GH treatment-naive patients with TS
      from the American Norditropin Studies: Web-enabled Research (ANSWER) Program(r)
      Registry were analyzed at baseline, 4 months, and annually. RESULTS: Three
      hundred and eighty-two patients with TS had a baseline mean (+/-SD) HSDS of -2.6
      +/- 0.9. Patients received short-term (1 year), long-term (<3 years), and
      extended GH treatment (>=3 years, mean = 4.54 years), resulting in 40.2% (n =
      99/246), 60.5% (n = 69/114), and 62.3% (n = 86/138) of the patients achieving
      HSDS >-2. Patients starting GH at a younger age experienced better growth
      response, regardless of treatment duration. Change in HSDS from baseline
      (DeltaHSDS) at 4 months correlated positively with DeltaHSDS at 1 and 3 years,
      and DeltaHSDS at 1 year with DeltaHSDS at 3 years (p values from 0.0017
      to<0.0001). CONCLUSIONS: Height gains in patients with TS during short-term
      treatment were found to be highly predictive of longer-term results. Continuation
      of GH treatment (>=3 years) resulted in 62.3% of the patients achieving an HSDS
      within the normal population range, indicating the clinical importance of early
      initiation and continuation of GH treatment in patients with TS.

PMID- 22156542
TI  - Long-term efficacy and safety of two doses of growth hormone in short Japanese
      children born small for gestational age.
AB  - BACKGROUND/AIMS: To investigate the long-term efficacy and safety of two doses
      (33 and 67 MUg/kg/day) of growth hormone (GH) in short Japanese children born
      small for gestational age (SGA). METHODS: 96 children born SGA (age 3 to <8
      years) were randomized to GH at 33 or 67 MUg/kg/day for 104 weeks, or to an
      untreated control (UC) group for 52 weeks. After 52 weeks, the UC group was
      randomized to GH at a dose of 33 or 67 MUg/kg/day for a 156-week extension study.
      Initial treatment groups continued unchanged for the extension phase. Efficacy
      was evaluated by change in height SDS for chronological age from baseline to
      208/260 weeks. RESULTS: After 208 weeks, change in height SDS from baseline
      (least square (LS) means (SE)) was 1.01 (0.47) and 1.99 (0.67) in the UC 33 and
      UC 67 MUg/kg/day groups, respectively. After 260 weeks, change in height SDS from
      baseline was 1.22 (0.51) and 2.01 (0.64) in the 33 and 67 MUg/kg/day groups,
      respectively. Insulin-like growth factor-1 levels were significantly higher in
      the groups receiving 67 MUg/kg/day but largely remained within normal limits (-2
      to +2 SDS). CONCLUSION: Long-term continuous GH treatment was well tolerated and
      effective in improving height SDS. Improvements were dose-dependent and
      significantly higher at 67 than 33 MUg/kg/day.

PMID- 22156543
TI  - Evolution of IGF-1 in children born small for gestational age and with growth
      retardation, treated by growth hormone adapted to IGF-1 levels after 1 year.
AB  - AIM: This study was designed to estimate the percentage of growth hormone (GH)
      treated children born small for gestational age (SGA), with serum IGF-1 >2 SDS
      before and after GH dose adaptation. METHODS: SGA boys aged 4-9 and girls aged 4
      7 with a height <-2 SDS and an annual growth rate below the mean received a
      subcutaneous GH dose of 57 MUg/kg/day for 2 years. The GH dose was to be
      decreased by 30% in children with serum IGF-1 >2 SDS at 12 months and on the
      previous sample. The GH dose could be reduced a second time to 35 MUg/kg.day. IGF
      1 and IGFBP-3 dosages were centralized. RESULTS: Among the 49 (21 boys) children
      included in the study, 8 (16.3%) had an IGF-1 >2 SDS consecutively at 9 and 12
      months (95% CI 7.3, 29.7). The GH dose was decreased in 6/8 children. However,
      IGF-1 levels were elevated at several nonconsecutive determinations in 45% (95%
      CI 28.4, 56.6) of the patients. CONCLUSION: A high IGF-1 level is observed in 45%
      of the GH SGA-treated children with a relatively high dose of GH. A 30% reduction
      in the GH dose causes a decrease in IGF-1 below 2 SDS in most children.

PMID- 22156544
TI  - Hormonal management of complete androgen insensitivity syndrome from adolescence
      onward.
AB  - Complete androgen insensitivity syndrome (CAIS) represents a main disorder of sex
      development. Women with CAIS may have their gonads removed before, during or
      after adolescence, thus requiring hormonal replacement therapy to induce puberty
      and/or maintain secondary sexual characteristics, to optimize bone mass accrual,
      and to promote physical and social well-being. Usually estrogens are used for
      this purpose, but formulations and doses should be better defined in multicentric
      prospective studies. Some women started testostosterone as hormonal replacement
      therapy, but this practice remains anecdotal. Bone health remains a crucial
      aspect in the management of persons with CAIS, but few sound data are available
      to guide clinical practice.

PMID- 22156545
TI  - Diabetes mellitus affects biomechanical properties of the optic nerve head in the
      rat.
AB  - BACKGROUND: To investigate the effect of diabetes on the biomechanical behavior
      of the optic nerve head (ONH) and the peripapillary sclera (ppSc) in
      streptozocine-induced diabetic rats. METHODS: Diabetes mellitus was induced in 20
      Wistar rats using streptozocine. Twenty-five nondiabetic rats served as controls.
      Eyes were enucleated after 12 weeks and 2 strips of one eye were prepared
      containing ONH or ppSc. The stress-strain relation was measured in the stress
      range of 0.05-10 MPa using a biomaterial tester. RESULTS: At 5% strain the stress
      of the ONH in diabetic rats was 897+/-295 kPa and in the control group it was
      671+/-246 kPa; there was a significant difference between both groups (p=0.011).
      The stress of the diabetic ppSc (574+/-185 kPa) increased compared to that of the
      nondiabetic ppSc (477+/-171 kPa), but this did not reach statistical significance
      (p=0.174). The calculated tangent modulus at 5% strain was 11.79 MPa in the
      diabetic ONH and 8.77 MPa in the nondiabetic ONH; there was a significant
      difference between both groups (p=0.006). The calculated tangent modulus at 5%
      strain was 7.17 MPa in the diabetic ppSc and 6.12 MPa in the nondiabetic ppSc,
      without a statistically significant difference (p=0.09). CONCLUSION: In contrast
      to the ppSc, the ONH of diabetic rats showed a significant increase in stiffness
      compared to nondiabetic rats, which might be explained by nonenzymatic collagen
      cross-linking mediated by advanced glycation end products due to high blood
      glucose levels in diabetes. Further studies are needed to investigate if these
      biomechanical changes represent a detrimental risk factor for intraocular
      pressure regulation in diabetic glaucoma patients.

PMID- 22156546
TI  - Reduced phosphocholine and hyperpolarized lactate provide magnetic resonance
      biomarkers of PI3K/Akt/mTOR inhibition in glioblastoma.
AB  - The phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin
      (PI3K/Akt/mTOR) signaling pathway is activated in more than88% of glioblastomas
      (GBM). New drugs targeting this pathway are currently in clinical trials.
      However, noninvasive assessment of treatment response remains challenging. By
      using magnetic resonance spectroscopy (MRS), PI3K/Akt/mTOR pathway inhibition was
      monitored in 3 GBM cell lines (GS-2, GBM8, and GBM6; each with a distinct pathway
      activating mutation) through the measurement of 2 mechanistically linked MR
      biomarkers: phosphocholine (PC) and hyperpolarized lactate.(31)P MRS studies
      showed that treatment with the PI3K inhibitor LY294002 induced significant
      decreases in PC to 34 %+/- 9% of control in GS-2 cells, 48% +/- 5% in GBM8, and
      45% +/- 4% in GBM6. The mTOR inhibitor everolimus also induced a significant
      decrease in PC to 62% +/- 14%, 57% +/- 1%, and 58% +/- 1% in GS-2, GBM8, and GBM6
      cells, respectively. Using hyperpolarized (13)C MRS, we demonstrated that
      hyperpolarized lactate levels were significantly decreased following
      PI3K/Akt/mTOR pathway inhibition in all 3 cell lines to 51% +/- 10%, 62% +/- 3%,
      and 58% +/- 2% of control with LY294002 and 72% +/- 3%, 61% +/- 2%, and 66% +/-
      3% of control with everolimus in GS-2, GBM8, and GBM6 cells, respectively. These
      effects were mediated by decreases in the activity and expression of choline
      kinase alpha and lactate dehydrogenase, which respectively control PC and lactate
      production downstream of HIF-1. Treatment with the DNA damaging agent
      temozolomide did not have an effect on either biomarker in any cell line. This
      study highlights the potential of PC and hyperpolarized lactate as noninvasive MR
      biomarkers of response to targeted inhibitors in GBM.

PMID- 22156547
TI  - Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in
      immunocompetent primary central nervous system lymphoma (PCNSL).
AB  - The diagnosis of primary central nervous system lymphoma (PCNSL) by
      radiographical examination is often difficult because of its similarity to other
      brain tumors. To test whether interleukin-10 (IL-10) and IL-6 can be used to
      distinguish PCNSL from other brain tumors that are radiographically similar,
      cerebrospinal fluid (CSF) levels of IL-10 and IL-6 were measured in 66 patients
      with intracranial tumors (PCNSLs: 26 cases; other brain tumors: 40 cases). In the
      patients with PCNSLs, the median CSF levels of IL-10 and IL-6 were 27 pg/mL and
      5.4 pg/mL, respectively. The CSF IL-10 and IL-6 levels were significantly higher
      in PCNSLs than in the other brain tumors. To validate the diagnostic value of CSF
      IL-10 in PCNSL, we prospectively examined 24 patients with brain lesions that
      were suspected to be PCNSL. We observed that the CSF IL-10 levels were
      significantly higher in PCNSLs than in other brain tumors. At an IL-10 cutoff
      level of 9.5 pg/mL, the sensitivity and specificity were 71.0% and 100%,
      respectively. After therapy, the CSF IL-10 levels were decreased in all patients
      and were increased at relapse in most of these patients. Immunohistochemically,
      all PCNSLs, except for 1 unclassified PCNSL, expressed both IL-10 and IL-10
      receptor-A. In the patients with high CSF IL-10, IL-10 expression levels in tumor
      were relatively higher, compared with low CSF IL-10; however, there was no
      significant difference between these groups. In addition, elevated CSF level of
      IL-10 was significantly associated with having a shorter progression-free
      survival (hazard ratio, 3.37; 95% confidence interval, 0.985-11.528; log-rank, P=
      .038). These results indicate that the CSF level of IL-10 may be a useful
      diagnostic and prognostic biomarker in patients with PCNSLs.

PMID- 22156548
TI  - Pretransplant physical activity predicts all-cause mortality in kidney transplant
      recipients.
AB  - BACKGROUND: Low physical activity (PA) has been associated with higher rates of
      cardiovascular disease (CVD) and mortality in the general population. Despite the
      benefits of kidney transplantation, kidney transplant recipients (KTRs) remain at
      elevated risk for CVD and mortality compared to individuals without kidney
      disease. METHODS: A prospective cohort of 507 adult KTRs from three academic
      centers completed the Physical Activity Scale for the Elderly (PASE) at
      transplantation. PASE scores were divided into tertiles. RESULTS: PA was lower
      with older age, history of CVD, smoking, and diabetes. During the median 8-year
      follow-up period, 128 individuals died, among whom 101 had a functioning
      allograft. In multivariable Cox regression for all-cause mortality, greater PA
      was strongly associated with better survival (HR: 0.52 for most active vs.
      inactive tertiles, 95% CI: 0.31-0.87, p = 0.01). Secondary analyses, in which (1)
      death with a functioning graft was the primary outcome, and (2) PASE scores were
      converted to the metabolic equivalent of task, revealed similar results. We did
      not find an association between change of PA after transplantation and mortality.
      CONCLUSIONS: PA at the time of kidney transplantation is a strong predictor of
      all-cause mortality and death with graft function. Evaluation of PA level among
      kidney transplant candidates may be a useful method to risk-stratify patients for
      survival after kidney transplantation. Kidney transplant candidates and
      recipients should also be encouraged to be physically active.

PMID- 22156549
TI  - Molecular pathways: BCR-ABL.
AB  - Aberrant tyrosine kinase activity plays a critical role in many hematologic
      disorders, including chronic myeloid leukemia characterized by the constitutive
      activity of BCR-ABL. ABL therefore represents a crucial target for new
      therapeutic strategies. Here, we summarize the molecular pathways that are
      abnormally activated by the oncoprotein. Such pathways may provide additional
      opportunities to develop new drugs to overcome the resistance to tyrosine kinase
      inhibitors. In particular, the phosphoinositide 3-kinase (PI3K)/AKT pathway can
      be effectively blocked by mTOR inhibitors, and several compounds can hit the RAS
      pathway and the resulting mitogen-activated protein (MAP) extracellular signal
      regulated kinase (ERK)1/2 (MEK) and MAP kinase activation. Furthermore, mitotic
      kinases can be blocked by Aurora kinase inhibitors, and Pim kinases can be
      blocked by selective serine-threonine kinase inhibitors. Finally, the abnormal
      pathways that sustain the self-renewal of leukemic stem cells are described as
      possible targets to completely eradicate leukemic clones. Such pathways include
      the Hedgehog pathway, which can be blocked by Smoothened inhibitors, and the
      CXCR4/SDF1 axis, which can be targeted by specific antagonists.

PMID- 22156550
TI  - Development of the olfactory pathways in platypus and echidna.
AB  - The two groups of living monotremes (platypus and echidnas) have remarkably
      different olfactory structures in the adult. The layers of the main olfactory
      bulb of the short-beaked echidna are extensively folded, whereas those of the
      platypus are not. Similarly, the surface area of the piriform cortex of the
      echidna is large and its lamination complex, whereas in the platypus it is small
      and simple. It has been argued that the modern echidnas are derived from a
      platypus-like ancestor, in which case the extensive olfactory specializations of
      the modern echidnas would have developed relatively recently in monotreme
      evolution. In this study, the development of the constituent structures of the
      olfactory pathway was studied in sectioned platypus and echidna embryos and post
      hatchlings at the Museum fur Naturkunde, Berlin, Germany. The aim was to
      determine whether the olfactory structures follow a similar maturational path in
      the two monotremes during embryonic and early post-hatching ages or whether they
      show very different developmental paths from the outset. The findings indicate
      that anatomical differences in the central olfactory system between the short
      beaked echidna and the platypus begin to develop immediately before hatching,
      although details of differences in nasal cavity architecture emerge progressively
      during late post-hatching life. These findings are most consistent with the
      proposition that the two modern monotreme lineages have followed independent
      evolutionary paths from a less olfaction-specialized ancestor. The monotreme
      olfactory pathway does not appear to be sufficiently structurally mature at birth
      to allow olfaction-mediated behaviour, because central components of both the
      main and accessory olfactory system have not differentiated at the time of
      hatching.

PMID- 22156551
TI  - Results of introducing a rapid recovery program for total abdominal hysterectomy.
AB  - OBJECTIVE: To review the impact of implementing a rapid recovery protocol (RRP)
      for patients undergoing abdominal hysterectomy. SETTING: Metropolitan teaching
      hospital. POPULATION: Women undergoing abdominal hysterectomy for non-malignant
      indications. METHODS: We conducted a retrospective review of consecutive cases
      performed during study periods before and after the introduction of an elective
      rapid recovery program emphasizing regional anesthesia. To control for universal
      improvements in medical practice, charts from a comparable local hospital without
      an RRP were also reviewed. RESULTS: 400 charts were reviewed and 366 cases met
      inclusion criteria and had sufficient information. Patients were well matched for
      demographic and medical variables between the study periods and between the
      institutions. The median length of stay (LOS) fell dramatically from 3 (range 1
      12) days prior to RRP introduction to 1 (range 1-17) day after RRP (p < 0.001).
      LOS among patients at the 'control' institution remained unchanged at 3 days
      during the same time frame, indicating that external pressures contributed
      minimally to the observed changes. There were no significant differences in
      estimated blood loss, duration of surgery, or complication rate between the
      groups in either time period. CONCLUSIONS: Introducing a rapid recovery program
      was associated with shorter hospitalization and did not appear to compromise
      surgical outcome.

PMID- 22156552
TI  - Obestatin: an interesting but controversial gut hormone.
AB  - Obestatin is a 23-amino acid peptide hormone released from the stomach and is
      present not only in the gastrointestinal tract, but also in the spleen, mammary
      gland, breast milk and plasma. Obestatin appears to function as part of a complex
      gut-brain network whereby hormones and substances from the stomach and intestines
      signal the brain about satiety or hunger. In contrast to ghrelin, which causes
      hyperphagia and obesity, obestatin appears to act as an anorectic hormone,
      decreasing food intake and reducing body weight gain. Further studies have shown
      that obestatin is also involved in improving memory, regulating sleep, affecting
      cell proliferation, increasing the secretion of pancreatic juice enzymes and
      inhibiting glucose-induced insulin secretion. This hormone has not only been
      studied in the field of physiology but also in the fields of obesity and diabetes
      mellitus, and in patients with psychogenic eating disorders. Obestatin has a role
      in regulating the cell cycle by exerting proliferative effects that may be seen
      in cell physiology and oncology. Given the current controversy regarding the
      effects of obestatin and its cognate ligand, this article provides the latest
      review of the physiological and pathological characteristics of this hormone.

PMID- 22156553
TI  - Altered microRNA expression profiles in retinas with diabetic retinopathy.
AB  - Rats with streptozotocin (STZ)-induced diabetes were studied in order to identify
      abnormal microRNA (miRNA) expression profiles in diabetic retinopathy (DR) and to
      ascertain miRNAs associated with DR. Histopathologically, we observed
      characteristic features of DR in rats at 10 weeks after STZ injection.
      Investigation of miRNA expression profiles in the retinas of control and diabetic
      rats using miRNA microarrays revealed that many miRNAs were abnormally expressed
      in DR. On the basis of their fold changes and probability values, a total of 37
      miRNAs were selected for further validation by real-time PCR analysis. The
      results showed that 11 miRNAs were significantly upregulated and 6 miRNAs were
      notably downregulated in DR. Furthermore, these changes in retinal miRNA
      expression levels paralleled the course of DR. Levels of miR-182, miR-96, miR
      183, miR-211, miR-204, and miR-124 were significantly increased during the
      progress of DR, whereas miR-10b, miR-10a, miR-219-2-3p, miR-144, miR-338, and miR
      199a-3p were significantly decreased. Our data indicate that the aberrant miRNA
      expression profiles in DR are associated with the development of DR. Modulation
      of retinal miRNA expression levels may provide a potential therapeutic strategy
      for DRs.

PMID- 22156554
TI  - Identifying earlier Alzheimer's disease: insights from the preclinical and
      prodromal phases.
AB  - Alzheimer's disease (AD) has been traditionally conceptualized as a
      clinicopathological entity, its definite diagnosis requiring the presence of
      characteristic pathology together with a dementia clinical picture. The fact that
      certain AD biomarkers show an acceptable sensitivity and specificity to detect AD
      pathology has shifted the diagnostic paradigm towards a clinicobiological
      approach. The objective of this paper is to present recent data that show how
      cerebrospinal fluid (CSF) biomarkers behave in preclinical AD. These studies have
      been performed in presymptomatic subjects (PreS) and asymptomatic subjects at
      risk for the disease (AsymR). In brief, the results show in PreS subjects that
      CSF biomarkers present a positive correlation with time to disease onset to reach
      floor levels at symptom onset. In addition, memory performance presents distinct
      associations in the AD continuum, being related to Abeta(1-42) levels in AsymR
      subjects and to t-tau and p-tau in prodromal AD. Furthermore, an increase in
      cortical thickness of typical AD areas was observed when mean Abeta(1-42) levels
      were still within the normal range in PreS subjects, or they presented
      transitional values in AsymR subjects. Overall, these findings suggest that the
      preclinical stage is biologically active and that there may be structural changes
      when amyloid is starting its deposition.

PMID- 22156555
TI  - A systematic review of the effectiveness of advance care planning interventions
      for people with cognitive impairment and dementia.
AB  - BACKGROUND: advance care planning (ACP) allows a patient to state their
      preferences for care, so that if in future they cannot make decisions their
      wishes are known. Our aim was to review systematically the effectiveness of ACP
      interventions in people with cognitive impairment and dementia. METHODS:
      systematic searches of key electronic databases, supplemented by hand searches of
      reference lists and consultation with experts. Two independent reviewers
      undertook screening, data extraction and quality assessment. RESULTS: four
      studies were included; three allocated providers randomly to intervention or
      control arm. All took place in nursing homes. Three studies reported formal
      processes of capacity assessment, only up to 36% of participants were judged to
      have capacity. Three studies reported positive findings in terms of documentation
      of patient preferences for care. Two studies reported significant reductions in
      hospitalisation rates; a third found increased use of hospice services in the
      intervention group. A meta-analysis could not be carried out due to heterogeneity
      of outcome measures. CONCLUSIONS: there is limited evidence for the effectiveness
      of ACP in people with cognitive impairment/dementia in terms of ACP documentation
      and health-care use. In terms of capacity to discuss ACP, nursing home settings
      may be too late for people with dementia.

PMID- 22156556
TI  - Predicting late-life disability and death by the rate of decline in physical
      performance measures.
AB  - BACKGROUND: the rate of performance decline may influence the risk of disability
      or death. METHODS: for 4,182 Cardiovascular Health Study participants, we used
      multinomial Poisson log-linear models to assess the contribution of physical
      performance in 1998-99, and the rate of performance change between 1992-93 and
      1998-99, to the risk of death or disability in 2005-06 in three domains:
      mobility, upper-extremity function (UEF) and activities of daily living (ADL). We
      evaluated performance in finger-tapping, grip strength, stride length, gait speed
      and chair stands separately and together for each outcome, adjusting for age,
      gender, race and years of disability in that outcome between 1992-93 and 1998-99.
      RESULTS: participants' age averaged 79.4 in 1998-99; 1,901 died over 7 years.
      Compared with the lowest change quintile in stride length, the highest quintile
      had a 1.32 relative risk (RR) of ADL disability (95% CI: 1.16 -1.96) and a 1.27
      RR of death (95% CI: 1.07 -1.51). The highest change quintile for grip strength
      increased the risk of ADL disability by 35% (95% CI: 1.13 -1.61) and death by 31%
      (95% CI: 1.16 -1.49), compared with the lowest quintile. The annual change in
      stride length and grip strength also predicted disability in mobility and UEF.
      CONCLUSION: performance trajectories independently predict death and disability.

PMID- 22156557
TI  - Association between statin medication use and improved outcomes during inpatient
      rehabilitation in older people.
AB  - BACKGROUND: statin drugs may induce skeletal myopathy, but might also have the
      potential to improve rehabilitation outcomes by improving sarcopenia or by
      preventing intercurrent illness. We examined the association between statin use
      and functional outcomes in the rehabilitation of older people. METHODS:
      retrospective cohort study using routinely collected clinical data. Admissions to
      Royal Victoria Hospital, Dundee for inpatient rehabilitation over a 10-year
      period were identified. Data were available regarding demographics, statin
      therapy, antiplatelet therapy, admission and discharge Barthel scores, length of
      stay and comorbid disease. Multivariate analyses were performed to examine the
      difference between admission and discharge Barthel score in patients taking
      statins compared with those not taking statins. RESULTS: a total of 3,422
      patients were included. Mean age was 81.4 years; 40% were male. Baseline Barthel
      scores were similar in the statin/non-statin groups, respectively (10.4/20 versus
      10.3/20, P = 0.57). Improvement in the Barthel score between admission and
      discharge was greater in the statin than non-statin group (3.59 versus 4.30
      points, P < 0.001) after adjustment for age, sex, baseline Barthel score and
      comorbid disease. CONCLUSION: statin use was associated with improved Barthel
      scores on discharge from rehabilitation. This gain could contribute to improved
      outcomes as part of the rehabilitation package and requires further prospective
      investigation.

PMID- 22156558
TI  - Physical performance, sarcopenia and respiratory function in older patients with
      chronic obstructive pulmonary disease.

PMID- 22156559
TI  - Older individuals with diabetes have an increased risk of recurrent falls:
      analysis of potential mediating factors: the Longitudinal Ageing Study Amsterdam.
AB  - OBJECTIVES: to compare the incidence of recurrent falls in older people with and
      without diabetes, and to examine diabetes- and fall-related risk factors
      explaining the increased risk of recurrent falls associated with diabetes.
      METHODS: population-based cohort study of 1,145 (85 with diabetes) community
      dwelling participants, aged >=65 years, from The Longitudinal Aging Study
      Amsterdam (LASA). Falls were assessed prospectively (every 3 months) during a 3
      year follow-up period. Incidence of recurrent falls was estimated with Poisson
      regression analyses. The associations between diabetes and time to recurrent
      falls, defined as at least two falls occurring within a 6-month period, and the
      potential explanatory role of several risk factors herein, were analysed with the
      use of Cox-regression models. RESULTS: during a mean follow-up of 139 weeks,
      30.6% of the individuals with and 19.4% of the individuals without diabetes fell
      recurrently [incidence rate of 129.7 versus 77.4 per 1,000 persons-years,
      respectively, HR = 1.67 (95% CI: 1.11-2.51)]. Adjustments for potential
      confounders did not change the increased risk associated with diabetes [HR = 1.63
      (1.06-2.52)]. Factors that partly explained this increased risk were: greater
      number of medication, higher levels of pain, poorer self-perceived health, lower
      physical activity and grip strength, more limitations in ADLs, lower-extremity
      physical performance and cognitive impairment. Altogether, these variables
      accounted for 47% of the increased risk of recurrent falls associated with
      diabetes [adjusted HR = 1.30 (0.79-2.11)]. CONCLUSION: fall prevention efforts
      targeting the factors identified above may need to be incorporated into the care
      and treatment of older individuals with diabetes.

PMID- 22156560
TI  - Cancer dormancy: a model of early dissemination and late cancer recurrence.
AB  - Cancer dormancy is a stage in tumor progression in which residual disease remains
      occult and asymptomatic for a prolonged period of time. Dormant tumor cells can
      be present as one of the earliest stages in tumor development, as well as a stage
      in micrometastases, and/or minimal residual disease left after an apparently
      successful treatment of the primary tumor. The general mechanisms that regulate
      the transition of disseminated tumor cells that have lain dormant into a
      proliferative state remain largely unknown. However, regulation of the growth
      from dormant tumor cells may be explained in part through the interaction of the
      tumor cell with its microenvironment, limitations in the blood supply, or an
      active immune system. An understanding of the regulatory machinery of these
      processes is essential for identifying early cancer biomarkers and could provide
      a rationale for the development of novel agents to target dormant tumor cells.
      This review focuses on the different signaling models responsible for early
      cancer dissemination and tumor recurrence that are involved in dormancy pathways.

PMID- 22156561
TI  - Chronic small vessel disease affects clinical outcome in patients with acute
      striatocapsular stroke.
AB  - BACKGROUND: Recovery from stroke is presumed to be a function of a cerebral
      network. Chronic small vessel disease (SVD) has been shown to disrupt this
      network's integrity and has been proposed as a predictor of poor outcome after
      stroke. We studied this hypothesis in patients with acute ischemic stroke of the
      striatocapsular region, an area of pronounced cortical and subcortical
      connectivity. METHODS: We identified 62 patients with isolated striatocapsular
      stroke from our stroke registry. The standardized workup included clinical rating
      according to the modified Rankin Scale (mRS) and MRI, rated according to the
      Fazekas scale for the extent of SVD, ranging from grade 0 to III. MRS at
      admission, at discharge, and a short-term recovery parameter (the difference
      between mRS at admission and discharge) were correlated with the extent of SVD.
      Comorbidity was assessed with the Charlson comorbidity index (CCI). RESULTS: SVD
      was graded 0 in 7%, I in 60%, II in 18%, and III in 16% of patients. The median
      mRS at discharge for the groups was 2, 1, 2 and 4, and the median recovery
      parameter was 2, 1, 1 and 0.5, respectively. The extent of SVD significantly
      correlated with both the mRS at discharge and the recovery parameter. While age
      was also a significant predictor of these outcome parameters, SVD severity was a
      significant predictor even after correction for age or CCI. CONCLUSIONS: SVD is a
      predictor of poor outcome and recovery in striatocapsular stroke, independent of
      age or comorbidity. Severe SVD disturbs the integrity of the cerebral network
      leading to aggravation of and poor recovery from neurological deficits.

PMID- 22156562
TI  - Obstructive parotitis secondary to an acute masseteric bend.
AB  - AIMS: To investigate 3 cases of chronic parotitis secondary to an acute bend in
      Stensen's duct caused by an enlargement of the masseteric space. RESULTS: Three
      female patients presented with symptoms consistent with obstructive parotitis
      including glandular swelling and tenderness during meals. A 10-year-old patient
      had unilateral facial swelling with enlargement of the masseter muscle and
      mandible later diagnosed as fibrous dysplasia. Salivary endoscopy showed an acute
      bend in Stensen's duct secondary to a mass effect. The patient's parotid swelling
      resolved following debulking of the mandibular mass and sialendoscopy with
      irrigation. Two adult patients with bilateral parotid involvement presented with
      bilateral masseteric hypertrophy and dental wear facets consistent with bruxism.
      Salivary endoscopy revealed bilateral kinking of Stensen's duct with jaw closure.
      Both patients improved symptomatically following nightly bite guard use and
      ultrasound-guided Botox injections of the masseter muscle and parotid.
      CONCLUSION: Obstructive parotitis is rarely caused by an acute masseteric bend.
      Diagnosis of a kinking Stensen's duct is aided with salivary endoscopy and
      imaging to determine the precipitating pathology. In the case of masseteric
      hypertrophy, symptomatic improvement can be achieved with Botox-induced atrophy
      of masseteric hypertrophy or with surgical reduction for associated fibrous
      dysplasia.

PMID- 22156563
TI  - An association between the serotonin transporter gene promoter polymorphism and
      smoking cessation among Japanese males.
AB  - The objective of this study was to replicate the associations between the
      serotonin transporter genotypes and smoking cessation and between these genotypes
      and long-term smoking cessation success (for 2 years or more). Two case-control
      designs were used in this study. The first case-control design consisted of 47 ex
      smokers (cases) and 94 smokers (controls). The second case-control design
      consisted of the 12 ex-smokers who had succeeded in long-term smoking cessation
      (cases) and the 24 smokers (controls). In the first design, there was no
      significant difference in allele frequency and genotype distribution between
      cases and controls. In the second design, the S/S genotype frequency was higher
      in cases than in controls, but the difference did not reach slightly statistical
      significance. The present study suggests that individuals with the S/S genotype
      are more inclined to achieve long-term smoking cessation than others.

PMID- 22156564
TI  - Lifestyle factors as predictors of general cardiovascular disease: use for early
      self-screening.
AB  - This study aims to examine the effectiveness of lifestyle factors in predicting
      general cardiovascular events and to investigate the feasibility of using the
      lifestyle model as a self-screening tool. The authors conducted a longitudinal
      study over a 10-year follow-up in Japan. Logistic regression analysis was used to
      create prediction models for general cardiovascular disease (CVD) death. The
      authors estimated the predictive power of the models by calculating the area
      under the receiver operating characteristic (AUROC) curve. The total of 6
      traditional and 5 lifestyle risk factors were significantly associated with the
      incidence of CVD events. Hazard ratios (HRs) were 0.26 (95% confidence interval
      [CI] = 0.17, 0.41) for regular physical activity, 0.57 (95% CI = 0.50, 0.67) for
      moderate- or high-intensity work, and 1.72 (95% CI = 1.31-2.26) for short sleep
      duration; the HRs for traditional and Western dietary patterns were 1.53 (95% CI
      = 1.12, 2.09) and 2.62 (95% CI = 1.46, 4.68), respectively. The AUROC curve was
      significantly different between the classic and lifestyle prediction models.
      These results suggest that lifestyle factors are significant predictors of CVD
      events. 

PMID- 22156565
TI  - History and biological significance of GPCR heteromerization in the
      neuroendocrine system.
AB  - G protein-coupled receptors (GPCRs) constitute a large family of seven
      transmembrane proteins that regulate major cellular functions. The important role
      of GPCRs in the neuroendocrine system is outlined by the great interest of
      pharmaceutical companies in developing new drugs targeting these receptors. GPCRs
      exist as monomers, but can also be organized in oligomeric structures composed of
      either homo- or heteromers. GPCR heteromerization may play an important role in
      modulating and fine-tuning GPCR function and signaling. The literature reports
      many examples of GPCR heteromers in vitro raising the question of the
      physiological relevance of these complexes in tissues. Considerable efforts are
      currently being directed towards conclusive evidence for the existence of GPCRs
      heteromers in vivo, a crucial step for the validation of the concept of GPCR
      heteromerization and future drug development. The present review will give a
      brief history of GPCR oligomerization and emphasize the importance and
      physiological relevance of GPCR heteromerization by discussing key examples of
      GPCR couples.

PMID- 22156566
TI  - Harmonization of measurement strategies for exposure to manufactured nano
      objects; report of a workshop.
AB  - The present paper summarizes the outcome of the discussions at the First
      International Scientific Workshop on Harmonization of Strategies to Measure and
      Analyze Exposure to (Manufactured) Nano-objects in Workplace Air that was
      organized and hosted by the Netherlands Organization for Applied Scientific
      Research (TNO) and the Institute for Occupational Safety and Health of the German
      Social Accident Insurance (IFA) (Zeist, The Netherlands, December 2010). It
      reflects the discussions by 25 international participants in the area of
      occupational (nano) exposure assessment from Europe, USA, Japan, and Korea on
      nano-specific issues related to the three identified topics: (i) measurement
      strategies; (ii) analyzing, evaluating, and reporting of exposure data; and (iii)
      core information for (exposure) data storage. Preliminary recommendations were
      achieved with respect to (i) a multimetric approach to exposure assessment, a
      minimal set of data to be collected, and basic data analysis and reporting as
      well as (ii) a minimum set of contextual information to be collected and
      reported. Other issues that have been identified and are of great interest
      include (i) the need for guidance on statistical approaches to analyze time
      series data and on electron microscopy analysis and its reporting and (ii) the
      need for and possible structure of a (joint) database to store and merge data. To
      make progress in the process of harmonization, it was concluded that achieving
      agreement among researchers on the preliminary recommendations of the workshop is
      urgent.

PMID- 22156567
TI  - Occupational exposure assessment in carbon nanotube and nanofiber primary and
      secondary manufacturers.
AB  - RESEARCH SIGNIFICANCE: Toxicological evidence suggests the potential for a wide
      range of health effects, which could result from exposure to carbon nanotubes
      (CNTs) and carbon nanofibers (CNFs). The National Institute for Occupational
      Safety and Health (NIOSH) has proposed a recommended exposure limit (REL) for
      CNTs/CNFs at the respirable size fraction. The current literature is lacking
      exposure information, with few studies reporting results for personal breathing
      zone (PBZ) samples in occupational settings. To address this gap, exposure
      assessments were conducted at six representative sites identified as CNT/CNF
      primary or secondary manufacturers. METHODS: Personal and area filter-based
      samples were collected for both the inhalable mass concentration and the
      respirable mass concentration of elemental carbon (EC) as well as CNT structure
      count analysis by transmission electron microscopy to assess exposures. When
      possible, full-shift PBZ samples were collected; area samples were collected on a
      task-based approach. RESULTS: The vast majority of samples collected in this
      study were below the proposed REL (7 MUg m(-3)). Two of the three secondary
      manufacturers' surveyed found concentrations above the proposed REL. None of the
      samples collected at primary manufacturers were found to be above the REL. Visual
      and microscopy-based evidence of CNTs/CNFs were found at all sites, with the
      highest CNT/CNF structure counts being found in samples collected at secondary
      manufacturing sites. The statistical correlations between the filter-based
      samples for the mass concentration of EC and CNT structure counts were examined.
      A general trend was found with a P-value of 0.01 and a corresponding Pearson
      correlation coefficient of 0.44. CONCLUSIONS: CNT/CNF concentrations were above
      the proposed NIOSH REL for PBZ samples in two secondary manufacturing facilities
      that use these materials for commercial applications. These samples were
      collected during dry powder handling processes, such as mixing and weighing,
      using fairly large quantities of CNTs/CNFs.

PMID- 22156568
TI  - Predictors of dermal exposures to polycyclic aromatic compounds among hot-mix
      asphalt paving workers.
AB  - OBJECTIVES: The primary objective of this study was to identify the source and
      work practices that affect dermal exposure to polycyclic aromatic compounds
      (PACs) among hot-mix asphalt (HMA) paving workers. METHODS: Four workers were
      recruited from each of three asphalt paving crews (12 workers) and were monitored
      for three consecutive days over 4 weeks for a total of 12 sampling days per
      worker (144 worker days). Two sampling weeks were conducted under standard
      conditions for dermal exposures. The third week included the substitution of
      biodiesel for diesel oil used to clean tools and equipment and the fourth week
      included dermal protection through the use of gloves, hat and neck cloth, clean
      pants, and long-sleeved shirts. Dermal exposure to PACs was quantified using two
      methods: a passive organic dermal (POD) sampler specifically developed for this
      study and a sunflower oil hand wash technique. Linear mixed-effects models were
      used to evaluate predictors of PAC exposures. RESULTS: Dermal exposures measured
      under all conditions via POD and hand wash were low with most samples for each
      analyte being below the limit of the detection with the exception of phenanthrene
      and pyrene. The geometric mean (GM) concentrations of phenanthrene were 0.69 ng
      cm(-2) on the polypropylene layer of the POD sampler and 1.37 ng cm(-2) in the
      hand wash sample. The GM concentrations of pyrene were 0.30 ng cm(-2) on the
      polypropylene layer of the POD sampler and 0.29 ng cm(-2) in the hand wash
      sample. Both the biodiesel substitution and dermal protection scenarios were
      effective in reducing dermal exposures. Based on the results of multivariate
      linear mixed-effects models, increasing frequency of glove use was associated
      with significant (P < 0.0001) reductions for hand wash and POD phenanthrene and
      pyrene concentrations; percent reductions ranged from 40 to 90%. Similar
      reductions in hand wash concentrations of phenanthrene (P = 0.01) and pyrene (P =
      0.003) were observed when biodiesel was substituted for diesel oil as a cleaning
      agent, although reductions were not significant for the POD sampler data.
      Although task was not a predictor of dermal exposure, job site characteristics
      such as HMA application temperature, asphalt grade, and asphalt application rate
      (tons per hour) were found to significantly affect exposure. Predictive models
      suggest that the combined effect of substituting biodiesel for diesel oil as a
      cleaning agent, frequent glove use, and reducing the HMA application temperature
      from 149 degrees C (300 degrees F) to 127 degrees C (260 degrees F) may reduce
      dermal exposures by 76-86%, varying by analyte and assessment method.
      CONCLUSIONS: Promising strategies for reducing dermal exposure to PACs among
      asphalt paving workers include requiring the use of dermal coverage (e.g. wearing
      gloves and/or long sleeves), substituting biodiesel for diesel oil as a cleaning
      agent, and decreasing the HMA application temperature.

PMID- 22156569
TI  - An assessment of workplace programmes designed to control inhalation risks using
      respiratory protective equipment.
AB  - OBJECTIVES: Few studies have assessed respiratory protective equipment (RPE)
      failures at the organizational level despite evidence to suggest that compliance
      with good practice may be low. The aim of this study was to develop an
      understanding of what current RPE programmes look like across industry and how
      this compares with good practice. METHODS: Twenty cross-industry site visits were
      conducted with companies that had RPE programmes in place. Visits involved
      management interviews to explore current RPE systems and procedures and the
      decision making underpinning these. Observations of RPE operatives were included
      followed by short interviews to discuss the behaviours observed. Post-site
      assessments jointly undertaken by an RPE scientist and psychologist produced
      ratings for each site on six critical aspects of RPE programmes
      (knowledge/awareness, selection, use, training/information, supervision, and
      storage/cleaning/maintenance). Overall ratings for theoretical competence (i.e.
      management knowledge of RPE) and practical control (i.e. actual RPE practice on
      the shop floor) were also given. Qualitative analysis was performed on all
      interview data. RESULTS: The performance of RPE programmes varied across
      industry. Fewer than half the companies visited were considered to have an
      acceptable level of theoretical competence and practical control. Four distinct
      groups emerged from the 20 sites studied, ranging from Learners (low theoretical
      competence and practical control--four sites), Developers (acceptable theoretical
      competence and low practical control--five sites), and Fortuitous (low
      theoretical competence and acceptable practical control--two sites), to
      Proficient (acceptable theoretical competence and practical control--nine sites).
      None of the companies visited were achieving optimal control through the use of
      RPE. Widespread inadequacies were found with programme implementation,
      particularly training, supervision, and maintenance. CONCLUSIONS: Our taxonomy
      based on the four groups (Learners, Developers, Fortuitous, and Proficient)
      provided a useful expert-informed tool for explaining the variation in
      performance of RPE programmes across industry. Although further research and
      development are required, this taxonomy offers a useful starting point for the
      development of practical tools that may assist managers in making the much-needed
      improvements to all facets of programme implementation, particularly training,
      supervision, and maintenance.

PMID- 22156570
TI  - Risks to young volunteers in international social projects.
AB  - BACKGROUND: The number of young volunteers in international social projects has
      increased significantly with governmental and non-governmental project support.
      This paper investigates the hypothesis that the preventative medical advice
      currently given prior to departure is inadequate because the risk profile of
      young persons (<30 years) differs from that of the general population. METHODS: A
      retrospective cross-sectional study was performed with participants of
      international social projects. A specific questionnaire was developed; inclusion
      criteria were age between 18 and 30 years at departure and a duration with the
      project of at least 6 months. RESULTS: One hundred and fifty-three data sets
      could be evaluated. Fifty-three percent were females; the destinations were as
      follows: 65.4% to Asia, 14.4% to Africa, and 10.5% to Latin America. The mean age
      was 20 years. Ninety percent of the participants received some kind of advice in
      travel medicine prior to departure. The vaccination rate was quite good, but
      pertussis (13.7%), yellow fever (80%), typhoid fever (54%), and rabies (49.7%)
      should be improved when travelling to high-risk regions. Food is a very important
      potential source of problems as 66% receive catering by the project, 56.2% from
      street stalls, and 44% were regularly invited to dine with locals. In Africa,
      only two-thirds of the participants of projects had regular access to safe water
      and the sanitary facilities were also poor; 51.7% of respondents reported new
      sexual contacts (one to more than six new partners). In most cases, condoms were
      used, but there were two unintended pregnancies. CONCLUSIONS: We conclude that
      young people need to be targeted with specialized advice for health and safety
      while abroad. This should highlight age-specific risks compared to advice for a
      more general population. Vaccination status should be improved for some regions
      and diseases.

PMID- 22156571
TI  - Use of the reciprocal calculation procedure for setting workplace emergency
      action levels for hydrocarbon mixtures and their relationship to lower explosive
      limits.
AB  - This paper proposes a novel use of the reciprocal calculation procedure (RCP) to
      calculate workplace emergency action levels (WEALs) for accidental releases of
      hydrocarbon mixtures. WEALs are defined here as the concentration in air that
      area monitors should alarm at to provide adequate warning and be sufficiently
      protective of health to allow at least enough time to don respiratory protective
      equipment (RPE) and escape. The rationale for the approach is analysed, and ways
      of defining suitable substance group guidance values (GVs) for input into the RCP
      are considered and compared. WEAL GVs could be based on: 3* RCP GVs (i.e. using
      the 3* rule), the 5* RCP GVs (i.e. using the 5* rule for calculating ceiling
      values), emergency exposure limits, or immediately dangerous to life or health
      values (IDLHs). Of these, the method of choice is to base WEAL GVs on health
      based IDLH values, which were developed for emergency situations in the
      workplace. However, IDLHs have only been set for 11 hydrocarbons, so the choice
      of GVs is also informed by comparison with possible GVs based on the other
      approaches. Using the proposed GVs, WEALs were calculated for various hydrocarbon
      mixtures, and the way they vary with the composition of the mixture was examined.
      Also, the level of health protection given by the current practice of setting
      emergency area alarms in the oil and gas industry at 10% of the lower explosive
      limit (LEL) was tested by comparing this with the WEAL. In the event of an
      accidental release, this comparison suggests that, provided that aromatics
      constitute <50% of the mixture, an alarm set at 10% LEL should provide adequate
      warning and be sufficiently protective of health to at allow at least enough time
      to don RPE and escape. In the absence of better information or specific acute
      toxicity concerns (such as the presence of hydrogen sulphide), it is proposed
      that the WEALs be used as a guide for assessing the adequacy of area alarm levels
      in respect of warning of an acute health risk. This work is exploratory (e.g.
      other rationales for setting GVs are possible) and the approach needs testing on
      further real-life samples. Although not explored here, the RCP approach may also
      lend itself to the calculation of in-house short-term exposure limits for
      hydrocarbon mixtures and other mixtures where the acute toxic end points of the
      components are similar.

PMID- 22156572
TI  - Potentially pathogenic bacteria and antimicrobial resistance in bioaerosols from
      cage-housed and floor-housed poultry operations.
AB  - BACKGROUND: Antibiotics are used in animal confinement buildings, such as cage
      housed (CH) and floor-housed (FH) poultry operations, to lower the likeliness of
      disease transmission. In FH facilities, antibiotics may also be used at sub
      therapeutic levels for growth promotion. Low levels of antibiotic create a
      selective pressure toward antimicrobial resistance (AMR) in chicken fecal
      bacteria. OBJECTIVE: The objective of this study was to compare bacteria and AMR
      genes in bioaerosols from CH and FH poultry facilities. METHODS: Bioaerosols were
      collected from 15 CH and 15 FH poultry operations, using stationary area samplers
      as well as personal sampling devices. Bacteria concentrations were determined by
      genus- or species-specific quantitative polymerase chain reaction (PCR) and AMR
      genes were detected using endpoint PCR. RESULTS: Enterococcus spp., Escherichia
      coli, and Staphylococcus spp. were significantly higher in bioaerosols of FH
      poultry operations than CH bioaerosols (P < 0.001) while Clostridium perfringens
      was significantly higher in area bioaerosols of CH operations than FH area
      bioaerosols (P < 0.05). Campylobacter spp. were detected only in bioaerosols of
      FH facilities. Zinc bacitracin resistance gene, bcrR, erythromycin resistance
      gene, ermA, and tetracycline resistance gene, tetA/C, were more prevalent in
      bioaerosols of FH facilities than CH bioaerosols (P < 0.01, P < 0.01, and P <
      0.05, respectively). CONCLUSIONS: Most bacteria are more concentrated and most
      AMR genes are more prevalent in bioaerosols of FH poultry operations, where
      growth-promoting antibiotics may be used.

PMID- 22156573
TI  - A persistent stress response to impeded axonal transport leads to accumulation of
      amyloid-beta in the endoplasmic reticulum, and is a probable cause of sporadic
      Alzheimer's disease.
AB  - BACKGROUND AND OBJECTIVE: Could a normal--but persistent--stress response to
      impeded axonal transport lead to late-onset Alzheimer's disease (AD)? Our results
      offer an affirmative answer, suggesting a mechanism for the abnormal production
      of amyloid-beta (Abeta), triggered by the slowed axonal transport at old age. We
      hypothesize that Abeta precursor protein (APP) is a sensor at the endoplasmic
      reticulum (ER) that detects, and signals to the nucleus, abnormalities in axonal
      transport. When persistently activated, due to chronically slowed-down transport,
      this signaling pathway leads to accumulation of Abeta within the ER. METHODS AND
      RESULTS: We tested this hypothesis with the neuronal cell line CAD. We show that,
      normally, a fraction of APP is transported into neurites by recruiting kinesin-1
      via the adaptor protein, Fe65. Under conditions that block kinesin-1-dependent
      transport, APP, Fe65 and kinesin-1 accumulate in the soma, and form a complex at
      the ER. This complex recruits active c-Jun N-terminal kinase (JNK), which
      phosphorylates APP at Thr(668). This phosphorylation increases the cleavage of
      APP by the amyloidogenic pathway, which generates Abeta within the ER lumen, and
      releases Fe65 into the cytoplasm. Part of the released Fe65 translocates into the
      nucleus, likely to initiate a gene transcription response to arrested transport.
      Prolonged arrest of kinesin-1-dependent transport could thus lead to accumulation
      and oligomerization of Abeta in the ER. CONCLUSION: These results support a model
      where the APP:Fe65 complex is a sensor at the ER for detecting the increased
      level of kinesin-1 caused by halted transport, which signals to the nucleus,
      while concomitantly generating an oligomerization-prone pool of Abeta in the ER.
      Our hypothesis could thus explain a pathogenic mechanism in AD.

PMID- 22156574
TI  - How to deal with measures of association: a short guide for the clinician.
AB  - When reading medical literature as a clinician, many different measures of
      association are presented. To judge whether results of studies can be applied to
      clinical practice, it is essential to understand and to be able to interpret the
      measure of association reported in the article. In this paper, we will present
      how to deal with the most commonly used measures of association including the
      risk and rate difference, number needed to treat, risk and rate ratio, hazard
      ratio and odds ratio. By means of examples, we will discuss the different
      measures of association for the three main study designs used in clinical
      research: randomized controlled trial, observational cohort study and case
      control study.

PMID- 22156575
TI  - KCTD8 gene and brain growth in adverse intrauterine environment: a genome-wide
      association study.
AB  - The most dramatic growth of the human brain occurs in utero and during the first
      2 years of postnatal life. Genesis of the cerebral cortex involves cell
      proliferation, migration, and apoptosis, all of which may be influenced by
      prenatal environment. Here, we show that variation in KCTD8 (potassium channel
      tetramerization domain 8) is associated with brain size in female adolescents
      (rs716890, P = 5.40 * 10(-09)). Furthermore, we found that the KCTD8 locus
      interacts with prenatal exposure to maternal cigarette smoking vis-a-vis cortical
      area and cortical folding: In exposed girls only, the KCTD8 locus explains up to
      21% of variance. Using head circumference as a proxy of brain size at 7 years of
      age, we have replicated this gene-environment interaction in an independent
      sample. We speculate that KCTD8 might modulate adverse effects of smoking during
      pregnancy on brain development via apoptosis triggered by low intracellular
      levels of potassium, possibly reducing the number of progenitor cells.

PMID- 22156576
TI  - Variants in ASB10 are associated with open-angle glaucoma.
AB  - The molecular events responsible for obstruction of aqueous humor outflow and the
      loss of retinal ganglion cells in glaucoma, one of the main causes of blindness
      worldwide, remain poorly understood. We identified a synonymous variant, c.765C>T
      (Thr255Thr), in ankyrin repeats and suppressor of cytokine signaling box
      containing protein 10 (ASB10) in a large family with primary open angle glaucoma
      (POAG) mapping to the GLC1F locus. This variant affects an exon splice enhancer
      site and alters mRNA splicing in lymphoblasts of affected family members.
      Systematic sequence analysis in two POAG patient groups (195 US and 977 German)
      and their respective controls (85 and 376) lead to the identification of 26 amino
      acid changes in 70 patients (70 of 1172; 6.0%) compared with 9 in 13 controls (13
      of 461; 2.8%; P = 0.008). Molecular modeling suggests that these missense
      variants change ASB10 net charge or destabilize ankyrin repeats. ASB10 mRNA and
      protein were found to be strongly expressed in trabecular meshwork, retinal
      ganglion cells and ciliary body. Silencing of ASB10 transcripts in perfused
      anterior segment organ culture reduced outflow facility by ~50% compared with
      control-infected anterior segments (P = 0.02). In conclusion, genetic and
      molecular analyses provide evidence for ASB10 as a glaucoma-causing gene.

PMID- 22156577
TI  - Genetic associations with lipoprotein subfractions provide information on their
      biological nature.
AB  - Adverse levels of lipoproteins are highly heritable and constitute risk factors
      for cardiovascular outcomes. Hitherto, genome-wide association studies revealed
      95 lipid-associated loci. However, due to the small effect sizes of these
      associations large sample numbers (>100 000 samples) were needed. Here we show
      that analyzing more refined lipid phenotypes, namely lipoprotein subfractions,
      can increase the number of significantly associated loci compared with bulk high
      density lipoprotein and low-density lipoprotein analysis in a study with
      identical sample numbers. Moreover, lipoprotein subfractions provide novel
      insight into the human lipid metabolism. We measured 15 lipoprotein subfractions
      (L1-L15) in 1791 samples using (1)H-NMR (nuclear magnetic resonance)
      spectroscopy. Using cluster analyses, we quantified inter-relationships among
      lipoprotein subfractions. Additionally, we analyzed associations with
      subfractions at known lipid loci. We identified five distinct groups of
      subfractions: one (L1) was only marginally captured by serum lipids and therefore
      extends our knowledge of lipoprotein biochemistry. During a lipid-tolerance test,
      L1 lost its special position. In the association analysis, we found that eight
      loci (LIPC, CETP, PLTP, FADS1-2-3, SORT1, GCKR, APOB, APOA1) were associated with
      the subfractions, whereas only four loci (CETP, SORT1, GCKR, APOA1) were
      associated with serum lipids. For LIPC, we observed a 10-fold increase in the
      variance explained by our regression models. In conclusion, NMR-based fine
      mapping of lipoprotein subfractions provides novel information on their
      biological nature and strengthens the associations with genetic loci. Future
      clinical studies are now needed to investigate their biomedical relevance.

PMID- 22156578
TI  - Molecular mechanisms leading to three different phenotypes in the cblD defect of
      intracellular cobalamin metabolism.
AB  - The cblD defect of intracellular vitamin B(12) metabolism can lead to isolated
      methylmalonic aciduria (cblD-MMA) or homocystinuria (cblD-HC), or combined
      methylmalonic aciduria and homocystinuria (cblD-MMA/HC). We studied the mechanism
      whereby MMADHC mutations can lead to three phenotypes. The effect of various
      expression vectors containing MMADHC modified to contain an enhanced
      mitochondrial leader sequence or mutations changing possible downstream sites of
      reinitiation of translation or mutations introducing stop codons on rescue of
      adenosyl- and methylcobalamin (MeCbl) formation was studied. The constructs were
      transfected into cell lines derived from various cblD patient's fibroblasts.
      Expression of 10 mutant alleles from 15 cblD patients confirmed that the nature
      and location of the mutations correlate with the biochemical phenotype. In cblD
      MMA/HC cells, improving mitochondrial targeting of MMADHC clearly increased the
      formation of adenosylcobalamin (AdoCbl) with a concomitant decrease in MeCbl
      formation. In cblD-MMA cells, this effect was dependent on the mutation and
      showed a negative correlation with endogenous MMADHC mRNA levels. These findings
      support the hypothesis that a single protein exists with two different functional
      domains that interact with either cytosolic or mitochondrial targets. Also a
      delicate balance exists between cytosolic MeCbl and mitochondrial AdoCbl
      synthesis, supporting the role of cblD protein as a branch point in intracellular
      cobalamin trafficking. Furthermore, our data indicate that the sequence after
      Met116 is sufficient for MeCbl synthesis, whereas the additional sequence between
      Met62 and Met116 is required for AdoCbl synthesis. Accordingly, western blot
      studies reveal proteins of the size expected from the stop codon position with
      subsequent reinitiation of translation.

PMID- 22156579
TI  - A critical role for the PAR-1/MARK-tau axis in mediating the toxic effects of
      Abeta on synapses and dendritic spines.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease and the
      leading cause of dementia in the elderly. Accumulating evidence supports soluble
      amyloid-beta (Abeta) oligomers as the leading candidate for the causative agent
      in AD and synapses as the primary site of Abeta oligomer action. However, the
      molecular and cellular mechanisms by which Abeta oligomers cause synaptic
      dysfunction and cognitive impairments remain poorly understood. Using primary
      cultures of rat hippocampal neurons as a model system, we show that the
      partitioning defective-1 (PAR-1)/microtubule affinity-regulating kinase (MARK)
      family kinases act as critical mediators of Abeta toxicity on synapses and
      dendritic spines. Overexpression of MARK4 led to tau hyperphosphorylation,
      reduced expression of synaptic markers, and loss of dendritic spines and
      synapses, phenotypes also observed after Abeta treatment. Importantly, expression
      of a non-phosphorylatable form of tau with the PAR-1/MARK site mutated blocked
      the synaptic toxicity induced by MARK4 overexpression or Abeta treatment. To
      probe the involvement of endogenous MARK kinases in mediating the synaptic
      toxicity of Abeta, we employed a peptide inhibitor capable of effectively and
      specifically inhibiting the activities of all PAR-1/MARK family members. This
      inhibitor abrogated the toxic effects of Abeta oligomers on dendritic spines and
      synapses as assayed at the morphological and electrophysiological levels. Our
      results reveal a critical role for PAR-1/MARK kinases in AD pathogenesis and
      suggest PAR-1/MARK inhibitors as potential therapeutics for AD and possibly other
      tauopathies where aberrant tau hyperphosphorylation is involved.

PMID- 22156580
TI  - Interaction between the ligand-binding domain of the LDL receptor and the C
      terminal domain of PCSK9 is required for PCSK9 to remain bound to the LDL
      receptor during endosomal acidification.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal
      growth factor homology domain repeat A of the low-density lipoprotein receptor
      (LDLR) at the cell surface and disrupts recycling of the internalized LDLR. As a
      consequence, the LDLR is rerouted to the lysosomes for degradation. Although
      PCSK9 may bind to an LDLR lacking the ligand-binding domain, at least three
      ligand-binding repeats of the ligand-binding domain are required for PCSK9 to
      reroute the LDLR to the lysosomes. In this study, we have studied the binding of
      PCSK9 to an LDLR with or without the ligand-binding domain at increasingly acidic
      conditions in order to mimic the milieu of the LDLR:PCSK9 complex as it
      translocates from the cell membrane to the sorting endosomes. These studies have
      shown that PCSK9 is rapidly released from an LDLR lacking the ligand-binding
      domain at pH in the range of 6.9-6.1. A similar pattern of release at acidic pH
      was also observed for the binding to the normal LDLR of mutant PCSK9 lacking the
      C-terminal domain. Together these data indicate that an interaction between the
      negatively charged ligand-binding domain of the LDLR and the positively charged C
      terminal domain of PCSK9 is required for PCSK9 to remain bound to the LDLR during
      the early phase of endosomal acidification as the LDLR translocates from the cell
      membrane to the sorting endosome.

PMID- 22156583
TI  - Fetoscopic laser surgery for twin-to-twin transfusion syndrome after 26 weeks of
      gestation.
AB  - OBJECTIVE: To compare the outcomes of twin-to-twin transfusion syndrome (TTTS)
      cases treated with fetoscopic laser coagulation of vascular anastomoses before 25
      + 6 weeks of gestation and between 26 and 28 weeks of gestation. MATERIAL AND
      METHODS: 28 consecutive cases of TTTS at Quintero stages II-IV treated with laser
      therapy between 26 + 0 and 28 + 6 weeks of gestation were compared with 324 cases
      treated between 15 + 0 and 25 + 6 weeks during a 3-year period in two centers.
      The following data were recorded and compared: duration of the fetoscopy, rate of
      complications (preterm labor before 28 weeks and before 32 weeks,
      chorioamnionitis, twin anemia-polycythemia syndrome and recurrent TTTS),
      gestational age at delivery and neonatal survival rate. RESULTS: The study groups
      were similar as regards Quintero staging and the frequency of anterior placental
      location (50.0 vs. 47.8%, p = 0.85 in late and conventional laser, respectively).
      There were no significant differences in the duration of surgery (29 vs. 30, p =
      0.27, respectively) and in the rates of any of the complications evaluated.
      Gestational age at delivery (33 vs. 33.3 weeks, p = 0.69) and neonatal survival
      of at least one fetus (92.3 vs. 88.6%, p = 0.24) were also similar. CONCLUSION:
      Fetoscopic laser coagulation for TTTS performed between 26 + 0 and 28 + 6 weeks
      of gestation was associated with similar outcomes as those observed in cases
      treated before 26 weeks.

PMID- 22156581
TI  - Cranial neural crest ablation of Jagged1 recapitulates the craniofacial phenotype
      of Alagille syndrome patients.
AB  - JAGGED1 mutations cause Alagille syndrome, comprising a constellation of clinical
      findings, including biliary, cardiac and craniofacial anomalies. Jagged1, a
      ligand in the Notch signaling pathway, has been extensively studied during
      biliary and cardiac development. However, the role of JAGGED1 during craniofacial
      development is poorly understood. Patients with Alagille syndrome have midface
      hypoplasia giving them a characteristic 'inverted V' facial appearance. This
      study design determines the requirement of Jagged1 in the cranial neural crest
      (CNC) cells, which encompass the majority of mesenchyme present during
      craniofacial development. Furthermore, with this approach, we identify the
      autonomous and non-autonomous requirement of Jagged1 in a cell lineage-specific
      approach during midface development. Deleting Jagged1 in the CNC using Wnt1-cre;
      Jag1 Flox/Flox recapitulated the midfacial hypoplasia phenotype of Alagille
      syndrome. The Wnt1-cre; Jag1 Flox/Flox mice die at postnatal day 30 due to
      inability to masticate owing to jaw misalignment and poor occlusion. The etiology
      of midfacial hypoplasia in the Wnt1-cre; Jag1 Flox/Flox mice was a consequence of
      reduced cellular proliferation in the midface, aberrant vasculogenesis with
      decreased productive vessel branching and reduced extracellular matrix by
      hyaluronic acid staining, all of which are associated with midface anomalies and
      aberrant craniofacial growth. Deletion of Notch1 from the CNC using Wnt1-cre;
      Notch1 F/F mice did not recapitulate the midface hypoplasia of Alagille syndrome.
      These data demonstrate the requirement of Jagged1, but not Notch1, within the
      midfacial CNC population during development. Future studies will investigate the
      mechanism in which Jagged1 acts in a cell autonomous and cell non-autonomous
      manner.

PMID- 22156584
TI  - Epigenetic-targeted drug discovery: from the guest editors.

PMID- 22156588
TI  - Linking amyloid-beta and tau: amyloid-beta induced synaptic dysfunction via local
      wreckage of the neuronal cytoskeleton.
AB  - BACKGROUND: In Alzheimer's disease (AD), amyloid-beta (Abeta) is the major
      component of extracellular plaques, whereas the microtubule-associated protein
      tau forms the main component of intracellular tangles. In contrast to
      frontotemporal dementias and other neurodegenerative diseases, both proteins form
      pathological aggregates and are considered key players for the development of AD.
      However, the connection between Abeta and tau and the functional loss of neurons
      and synapses, which ultimately lead to cognitive impairments, is still not well
      understood. OBJECTIVES: Making use of primary neurons exposed to Abeta oligomers,
      we sought to determine how tau mediates the Abeta-induced neuronal dysfunction.
      Additionally, we asked how the microtubule cytoskeleton is involved in the
      combined Abeta and tau toxicity. METHODS: We exposed mature primary rat neurons
      with developed synapses to Abeta oligomers and used immunofluorescence and
      electron microscopy to investigate tau, actin, neurofilament and microtuble
      cytoskeleton changes. RESULTS: Abeta oligomers preferentially associate with
      synapses, notably dendritic spines, throughout the neuronal cell culture. As a
      consequence, endogenous tau gets missorted from the axonal into the
      somatodendritic compartment in a subset of cells. These missorted cells also
      display missorting of neurofilaments, and a dramatic loss of microtubules, which
      can be prevented by the microtubule stabilizer taxol. CONCLUSIONS: Abeta causes
      tau missorting, loss of neuronal cell polarity and loss of dendritic
      microtubules. This in turn leads to impaired organelle/mitochondria transport,
      whereby synapses cannot be maintained properly and eventually decay. The data
      support the view that the microtubule cytoskeleton is a valid therapeutic target
      in AD.

PMID- 22156587
TI  - Association of hypo- and hyperkalemia with disease progression and mortality in
      males with chronic kidney disease: the role of race.
AB  - BACKGROUND/AIMS: Abnormal serum potassium is associated with higher mortality in
      dialysis patients, but its impact on outcomes in predialysis chronic kidney
      disease (CKD) is less clear. Furthermore, blacks with normal kidney function have
      lower urinary potassium excretion, but it is unclear if such differences have a
      bearing on race-associated outcomes in CKD. METHODS: We studied predialysis
      mortality and slopes of estimated glomerular filtration rate, eGFR) associated
      with serum potassium in 1,227 males with CKD. Mortality was examined in time
      dependent Cox models, and slopes of eGFR in linear mixed effects models with
      adjustments for case mix and laboratory values. RESULTS: Both hypo- and
      hyperkalemia were associated with mortality overall and in 933 white patients,
      but in 294 blacks hypokalemia was a stronger death predictor. Hypokalemia was
      associated with loss of kidney function independent of race: a 1 mEq/l lower
      potassium was associated with an adjusted difference in slopes of eGFR of -0.13
      ml/min/1.73 m(2)/year (95% CI: -0.20 to -0.07), p < 0.001. CONCLUSION: Hypo- and
      hyperkalemia are associated with higher mortality in CKD patients. Blacks appear
      to better tolerate higher potassium than whites. Hypokalemia is associated with
      faster CKD progression independent of race. Hyperkalemia management may warrant
      race-specific consideration, and hypokalemia correction may slow CKD progression.

PMID- 22156589
TI  - Preface. Use of genome-wide oligonucleotide- or SNP-array platforms has widened
      the spectrum of detectable human genomic variation.

PMID- 22156591
TI  - Rapamycin combined with TGF-beta converts human invariant NKT cells into
      suppressive Foxp3+ regulatory cells.
AB  - Invariant NKT (iNKT) cells constitute a versatile T cell subset with important
      regulatory functions, which are thought to result essentially from their capacity
      to promptly produce cytokines that influence the Th1/Th2 balance. In this study,
      we report that these cells can also express Foxp3, an important transcriptional
      regulator associated with suppressive activity, once they have been exposed to
      TGF-beta. Foxp3 was expressed by iNKT cells from both peripheral and cord blood.
      CD4(+) iNKT cells acquired Foxp3 expression preferentially, although a lower
      proportion of their CD4(-) counterpart also became positive. All Foxp3(+) iNKT
      cells displayed CD25 but not necessarily CTLA4 or GITR, regardless of the
      upregulation of these markers in the presence of TGF-beta. Exposure to TGF-beta
      decreased IL-4 and IFN-gamma production while increasing IL-10, independently
      from Foxp3 expression. IL-17 was not detected. TGF-beta induced high levels of
      Foxp3, but no suppressor activity, which emerged only in the presence of
      rapamycin. Peripheral and cord blood Foxp3(+) iNKT cells suppressed the
      proliferation of conventional autologous and heterologous CD4(+) T cells equally,
      in a cell contact-dependent and Ag-independent manner. Our findings demonstrate
      that human iNKT cells become suppressive in the presence of TGF-beta plus
      rapamycin, thus adding a new facet to their complex functional properties.

PMID- 22156590
TI  - Loss of B7-H1 expression by recipient parenchymal cells leads to expansion of
      infiltrating donor CD8+ T cells and persistence of graft-versus-host disease.
AB  - Previous experimental studies have shown that acute graft-versus-host disease
      (GVHD) is associated with two waves of donor CD8(+) T cell expansion. In the
      current studies, we used in vivo bioluminescent imaging, in vivo BrdU labeling,
      and three different experimental GVHD systems to show that B7-H1 expression by
      recipient parenchymal cells controls the second wave of alloreactive donor CD8(+)
      T cell expansion and the associated second phase of GVHD. Loss of B7-H1
      expression by parenchymal cells during the course of GVHD was associated with
      persistent proliferation of donor CD8(+) T cells in GVHD target tissues and
      continued tissue injury, whereas persistent expression of B7-H1 expression by
      parenchymal cells led to reduced proliferation of donor CD8(+) T cells in GVHD
      target tissues and resolution of GVHD. These studies demonstrate that parenchymal
      cell expression of B7-H1 is required for tolerizing infiltrating T cells and
      preventing the persistence of GVHD. Our results suggest that therapies designed
      to preserve or restore expression of B7-H1 expression by parenchymal tissues in
      the recipient could prevent or ameliorate GVHD in humans.

PMID- 22156592
TI  - Streptococcus pneumoniae stimulates a STING- and IFN regulatory factor 3
      dependent type I IFN production in macrophages, which regulates RANTES production
      in macrophages, cocultured alveolar epithelial cells, and mouse lungs.
AB  - Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. In
      this study, we examine an innate immune recognition pathway that senses
      pneumococcal infection, triggers type I IFN production, and regulates RANTES
      production. We found that human and murine alveolar macrophages as well as murine
      bone marrow macrophages, but not alveolar epithelial cells, produced type I IFNs
      upon infection with S. pneumoniae. This response was dependent on the pore
      forming toxin pneumolysin and appeared to be mediated by a cytosolic DNA-sensing
      pathway involving the adapter molecule STING and the transcription factor IFN
      regulatory factor 3. Indeed, DNA was present in the cytosol during pneumococcal
      infection as indicated by the activation of the AIM2 inflammasome, which is known
      to sense microbial DNA. Type I IFNs produced by S. pneumoniae-infected
      macrophages positively regulated gene expression and RANTES production in
      macrophages and cocultured alveolar epithelial cells in vitro. Moreover, type I
      IFNs controlled RANTES production during pneumococcal pneumonia in vivo. In
      conclusion, we identified an immune sensing pathway detecting S. pneumoniae that
      triggers a type I IFN response and positively regulates RANTES production.

PMID- 22156593
TI  - gammadelta T cell homing to skin and migration to skin-draining lymph nodes is
      CCR7 independent.
AB  - In most species, gammadelta T cells preferentially reside in epithelial tissues
      like the skin. Lymph duct cannulation experiments in cattle revealed that bovine
      dermal gammadelta T cells are able to migrate from the skin to the draining lymph
      nodes via the afferent lymph. For alphabeta T cells, it is generally accepted
      that epithelial and mucosal tissue egress is regulated by expression of the CCR7
      chemokine receptor. In this study, we tracked the migratory route of bovine lymph
      derived gammadelta T cells and examined their CCR7 cell surface expression in
      several compartments along this route. Total lymph cells from afferent and
      efferent origin were labeled with PKH fluorescent dyes and injected into the
      bloodstream. PKH(+) cells already reappeared in the afferent lymph after 4 h. The
      vast majority of the PKH(+) cells retrieved from the afferent lymph were of the
      WC1(+) gammadelta T cell phenotype, proving that this PKH(+) gammadelta T cell
      subset is able to home to and subsequently exit the skin. PKH(+) gammadelta T
      cells from afferent and efferent lymph lack CCR7 surface expression and display
      high levels of CD62L compared with CD4 T cells, which do express CCR7. Skin
      homing receptors CCR4 and CCR10 in contrast were transcribed by both CD4 and
      gammadelta T cells. Our findings suggest that gammadelta T cell skin egress and
      migration into the peripheral lymphatics is CCR7-independent and possibly
      mediated by CD62L expression.

PMID- 22156594
TI  - IL-10 limits parasite burden and protects against fatal myocarditis in a mouse
      model of Trypanosoma cruzi infection.
AB  - Chagas' disease is a zoonosis prevalent in Latin America that is caused by the
      protozoan Trypanosoma cruzi. The immunopathogenesis of cardiomyopathy, the main
      clinical problem in Chagas' disease, has been extensively studied but is still
      poorly understood. In this study, we systematically compared clinical,
      microbiologic, pathologic, immunologic, and molecular parameters in two mouse
      models with opposite susceptibility to acute myocarditis caused by the myotropic
      Colombiana strain of T. cruzi: C3H/HeSnJ (100% mortality, uncontrolled
      parasitism) and C57BL/6J (<10% mortality, controlled parasitism). T. cruzi
      induced differential polarization of immunoregulatory cytokine mRNA expression in
      the hearts of C57BL/6J versus C3H/HeSnJ mice; however, most differences were
      small. The difference in IL-10 expression was exceptional (C57BL/6J 8.7-fold
      greater than C3H/HeSnJ). Consistent with this, hearts from infected C57BL/6J
      mice, but not C3H/HeSnJ mice, had a high frequency of total IL-10-producing
      CD8(+) T cells and both CD4(+) and CD8(+) subsets of IFN-gamma(+)IL-10(+) double
      producing T cells. Furthermore, T. cruzi infection of IL-10(-/-) C57BL/6J mice
      phenocopied fatal infection in wild-type C3H/HeSnJ mice with complete loss of
      parasite control. Adoptive transfer experiments indicated that T cells were a
      source of protective IL-10. Thus, in this system, IL-10 production by T cells
      promotes T. cruzi control and protection from fatal acute myocarditis.

PMID- 22156596
TI  - Relation between depressed mood, somatic comorbidities and health service
      utilisation in older adults: results from the KORA-Age study.
AB  - BACKGROUND: prior literature suggests that comorbidity with depression
      significantly worsens the health state of people with chronic diseases.
      OBJECTIVE: the present study examines whether depressed mood increased medical
      care use for patients with a comorbid physical disease. DESIGN, SETTING AND
      SUBJECTS: the study was a population-based study (KORA-Age), with 3,938
      participants aged 64-94. METHODS: we investigated differences in health services
      use in participants with and without depressed mood (Geriatric Depression Scale).
      A further adjustment for disease was done and differences were examined with the
      Mann-Whitney U test. The incidence rate ratios (IRRs) for doctors' appointments
      or the number of days in hospital were explored with (zero-inflated) negative
      binomial regression models. RESULTS: there are increased self-neglecting
      behaviours and medical comorbidities in participants with depressed mood.
      Depressed mood increased participants' use of medical services (P < 0.0001).
      Among participants who visited the doctor during the last 3 months, those with
      depressed mood had more visits than those without depressed mood, irrespective of
      somatic comorbidities (P < 0.0001 and P < 0.05 for ill and healthy,
      respectively). Additionally, patients with coexisting depressed mood and physical
      disease visited the doctor's practice significantly more often. Having depressed
      mood significantly increases the likelihood for more doctor visits (IRR = 1.5, CI
      = 1.3-1.7) and longer hospital stays (IRR = 1.9, CI = 1.6-2.3). In participants
      with somatic comorbidities the risk is even greater (IRR = 1.6, CI = 1.3-2, for
      the number of doctors visits and IRR = 2, CI = 1.4-2.9, for the number of days in
      the hospital). CONCLUSIONS: results suggest that patients with depressed mood had
      increased use of health-care services overall, particularly those with somatic
      comorbidities.

PMID- 22156595
TI  - Mannose-binding lectin-associated serine protease-1 is a significant contributor
      to coagulation in a murine model of occlusive thrombosis.
AB  - Bleeding disorders and thrombotic complications constitute a major cause of death
      and disability worldwide. Although it is known that the complement and
      coagulation systems interact, no studies have investigated the specific role or
      mechanisms of lectin-mediated coagulation in vivo. FeCl(3) treatment resulted in
      intra-arterial occlusive thrombogenesis within 10 min in wild-type (WT) and
      C2/factor B-null mice. In contrast, mannose-binding lectin (MBL)-null and MBL
      associated serine protease (MASP)-1/-3 knockout (KO) mice had significantly
      decreased FeCl(3)-induced thrombogenesis. Reconstitution with recombinant human
      (rh) MBL restored FeCl(3)-induced thrombogenesis in MBL-null mice to levels
      comparable to WT mice, suggesting a significant role of the MBL/MASP complex for
      in vivo coagulation. Additionally, whole blood aggregation demonstrated increased
      MBL/MASP complex-dependent platelet aggregation. In vitro, MBL/MASP complexes
      were captured on mannan-coated plates, and cleavage of a chromogenic thrombin
      substrate (S2238) was measured. We observed no significant differences in S2238
      cleavage between WT, C2/factor B-null, MBL-A(-/-), or MBL-C(-/-) sera; however,
      MBL-null or MASP-1/-3 KO mouse sera demonstrated significantly decreased S2238
      cleavage. rhMBL alone failed to cleave S2238, but cleavage was restored when
      rMASP-1 was added to either MASP-1/-3 KO sera or rhMBL. Taken together, these
      findings indicate that MBL/MASP complexes, and specifically MASP-1, play a key
      role in thrombus formation in vitro and in vivo.

PMID- 22156597
TI  - Aspirin versus warfarin in atrial fibrillation: decision analysis may help
      patients' choice.
AB  - BACKGROUND: the primary prevention of ischaemic stroke in chronic non-valvular
      atrial fibrillation (AF) typically involves consideration of aspirin or warfarin.
      CHA(2)DS(2)-VASc estimates annual stroke rates for untreated AF patients, which
      are reduced by 60% with warfarin and by 20% with aspirin. HAS-BLED estimates
      annual rates of major bleeding on warfarin. The latter risk with aspirin is 0.5
      1.2% per year. HYPOTHESIS: given a 'warfarin, aspirin or no therapy' choice, AF
      patients will prefer the option that maximises the annual probability of not
      having a stroke and not having a major bleed. METHODS: decision tree applied to
      the 60 possible combinations of CHA(2)DS(2)-VASc and HAS-BLED scores. RESULTS:
      according to the pre-specified hypothesis, when CHA(2)DS(2)-VASc is <2, the
      balance of risk and benefit would advise no treatment; when CHA(2)DS(2)-VASc is 2
      or 3, warfarin would be best when HAS-BLED <2, otherwise no treatment would be
      advised; for CHA(2)DS(2)-VASc =4, warfarin would be best when HAS-BLED <3,
      otherwise no treatment would be advised and for CHA(2)DS(2)-VASc >=5, warfarin
      would be the preferred option if HAS-BLED <4, otherwise aspirin would be advised.
      CONCLUSION: this theoretical exercise illustrates the potential benefit of
      decision analysis in an area where high complexity and uncertainty still remain.

PMID- 22156598
TI  - Recurrent strokes caused by a malpositioned pacemaker lead.
AB  - This case report illustrates the case of a patient who developed recurrent
      strokes after a pace maker lead was inserted into his left ventricle. It was
      removed successfully by the cardiothoracic surgeons but he remained very
      dependent functionally. This case highlights the importance of always reviewing
      the electrocardiogram and chest radiograph after the insertion of a pacemaker as
      late diagnosis of this complication can leave the patient with significant
      morbidity.

PMID- 22156599
TI  - Insights into caspase-mediated apoptotic pathways induced by amyloid-beta in
      cerebral microvascular endothelial cells.
AB  - BACKGROUND: The vascular deposition of amyloid known as cerebral amyloid
      angiopathy (CAA)--an age-associated condition and a common finding in Alzheimer's
      disease--compromises cerebral blood flow, causing macro/microhemorrhages and/or
      cognitive impairment. Very little is known about the mechanisms causing CAA
      related degeneration of cerebral vascular cells. The Dutch E22Q familial amyloid
      beta (Abeta) variant is primarily associated with CAA, and manifests clinically
      with severe cerebral hemorrhages. OBJECTIVE: We aimed to determine the molecular
      mechanisms causing apoptosis of cerebral endothelial cells in the presence of
      wild-type Abeta40 or its vasculotropic E22Q variant. METHODS: We challenged human
      brain microvascular endothelial cells with both Abeta variants, and studied the
      apoptotic pathways triggered by these peptides. RESULTS: Caspase-mediated
      apoptotic pathways were elicited by both peptides within time frames correlating
      with their aggregation properties and formation of oligomeric/protofibrillar
      assemblies. Our data revealed a primary activation of caspase-8 (typically
      triggered by death receptors) with secondary engagement of caspase-9, with
      cytochrome C and apoptosis-inducing factor release from the mitochondria,
      suggesting the independent or synergistic engagement of extrinsic and intrinsic
      apoptotic mechanisms. CONCLUSION: Our data demonstrate the induction of caspase-8
      and caspase-9-dependent mitochondrial-mediated apoptotic pathways by Abeta
      oligomers/protofibrils in vascular cells, likely implicating a primary activation
      of death receptors.

PMID- 22156600
TI  - Monoclonal antibodies against the human somatostatin receptor subtypes 1-5:
      development and immunohistochemical application in neuroendocrine tumors.
AB  - BACKGROUND: Activation of somatostatin receptors (sstr1-5) by somatostatin and
      its analogues exerts an inhibitory effect on hormone secretion and provides the
      basis for the treatment of a range of endocrine diseases such as acromegaly,
      Cushing's disease and neuroendocrine tumors (NET). The lack of well-characterized
      commercially available sstr subtype-specific antibodies prevents routine
      identification of the sstr expression profile in patients. METHODS: We generated
      and characterized new mouse monoclonal antibodies (mAbs) targeting the five human
      sstr subtypes using ELISA and immunohistochemistry, and tested their suitability
      in formalin-fixed and paraffin-embedded (FFPE) human tissues and archival samples
      of normal pancreatic tissue and NET. RESULTS: All mAbs were highly specific with
      no cross-reactivity. The sstr1-5 immunoreactivity in gastrointestinal NET (n=67)
      was correlated with clinicopathologic data. With the exception of sstr3, NET were
      highly positive for all receptor subtypes (42, 63, 6, 32 and 65% of tumors were
      positive for sstr1, sstr2a, sstr3, sstr4 and sstr5, respectively). sstr1, sstr2a
      and sstr5 were present at the plasma membrane and in the cytoplasm of tumor
      cells, whereas sstr3 and sstr4 were almost exclusively cytoplasmic.
      Immunoreactivity of sstr1, sstr2a and sstr4 tended to decrease as tumor
      aggressiveness increased. sstr5 showed an opposite pattern, with higher staining
      in well-differentiated carcinomas compared with well-differentiated tumors. sstr5
      immunoreactivity was correlated with the presence of metastases and
      angioinvasion, suggesting a possible association with more aggressive behavior.
      CONCLUSION: Determination of the sstr1-5 by immunohistochemistry using subtype
      specific mAbs is feasible in FFPE tissue and may provide a tool for routine
      clinical practice.

PMID- 22156601
TI  - Cigarette smoking and the risk of multiple sclerosis: a sibling case-control
      study in Isfahan, Iran.
AB  - AIMS: We aimed to study the smoking habits of multiple sclerosis (MS) patients
      and their healthy siblings in Isfahan province in Iran. METHODS: MS patients
      registered with the Isfahan MS society database were compared to their healthy
      siblings who served as controls. Data regarding the smoking habits of patients
      and their siblings were collected using a specially designed questionnaire.
      Conditional logistic regression was adopted to analyze the association of smoking
      with the risk of MS, adjusting for age and sex. RESULTS: There were 1,606
      participants with 516 cases and 1,090 controls. After adjustments for age and
      sex, subjects who were ever-smokers had a significant risk of developing MS [odds
      ratio (OR) 2.67; 95% confidence interval (CI) 1.70-4.21; p <0.001]. Past smokers
      (OR 8.83; 95% CI 3.98-19.60; p < 0.001) and current smokers (OR 1.84; 95% CI 1.10
      3.10; p = 0.021) had a significant risk for developing MS. Disease progression
      (current expanded disability status scale/disease duration) was not different
      between smokers and nonsmokers (0.54 +/- 0.42 vs. 0.49 +/- 0.48; p = 0.61).
      CONCLUSION: Using a sibling pair method our data confirm the association between
      smoking and MS. A degree of confounding due to overmatching between siblings was
      unavoidable, but any bias would be conservative and should have lessened the
      effect of smoking.

PMID- 22156602
TI  - Trends in avoidable mortality in Lithuania during 2001-2008 and their impact on
      life expectancy.
AB  - The process of the restructuring of health care system in Lithuania demonstrates
      the need to continue the monitoring of changes in avoidable mortality. OBJECTIVE:
      To assess the level of avoidable mortality as well as its changes over time in
      Lithuania during 2001-2008 and to define the impact of avoidable mortality on
      life expectancy. MATERIAL AND METHODS: The mortality data were taken from the
      Lithuanian Department of Statistics. Twelve avoidable causes of deaths (treatable
      and preventable) were analyzed. Mortality trends were assessed by computing the
      average annual percent change (AAPC). The shortening of average life expectancy
      was computed from survival tables. RESULTS: During the period 2001-2008, the
      avoidable mortality was increasing more significantly (AAPC 3.0%, P<0.05) than
      the overall mortality (AAPC 1.7%, P<0.05) in the population aged 5-64 years. The
      increasing trend was mainly determined by mortality from preventable diseases
      (AAPC 4.6%, P<0.05). The avoidable causes of death reduced the life expectancy by
      1.77 years (preventable by 1.12 and treatable by 0.63 years). Diversity in trends
      in mortality of different avoidable causes was disclosed. A declining trend in
      mortality caused by chronic rheumatic heart disease and lung cancer was observed
      for males (AAPC -22.6% and -2.1%, respectively; P<0.05). However, the mortality
      caused by liver cirrhosis was increasing for both genders (AAPC 16.1% for males
      and 17.6% for females, P<0.01) and that caused by tuberculosis - only for females
      (AAPC 7.8%, P<0.05). CONCLUSIONS: An increasing trend in avoidable mortality was
      observed. Deaths caused by the diseases that could have been prevented had the
      greatest impact on the increasing mortality and decreasing life expectancy.

PMID- 22156603
TI  - Skeletal muscle-derived stem cells: implications for cell-mediated therapies.
AB  - Current advances in stem cell research and innovative biological approaches in
      the field of tissue engineering and regenerative medicine could eventually
      translate into prospective clinical applications. Various adult organs and
      tissues harbor stem and progenitor cells that could potentially be used to
      repair, regenerate, and restore a variety of different tissues following acute
      injury or tissue destructive diseases. Skeletal muscle is a very convenient and
      plentiful source of somatic stem cells. It contains several distinct populations
      of myogenic stem cells including satellite cells that are mainly responsible for
      muscle growth and regeneration, and multipotent muscle-derived stem cells
      (MDSCs). Although both cell populations share some phenotypic similarities, MDSCs
      display a much greater differentiation potential in vitro and are capable of
      regenerating various tissues in vivo. Furthermore, these cells not only
      participate in the regeneration process by differentiating into tissue-specific
      cell types, but also promote endogenous tissue repair by secreting a multitude of
      trophic factors. In this article, we describe the biological aspects of MDSC
      isolation and characterization and provide an overview of potential therapeutic
      application of these cells for the treatment of cardiac and skeletal muscle
      injuries and diseases, urological dysfunction, and bone and cartilage defects. We
      also discuss major challenges and limitations currently faced by MDSC-based
      therapies that await resolution before these techniques can be applied
      clinically.

PMID- 22156604
TI  - Targeted therapy in patients with non-small cell lung cancer previously treated
      with chemotherapy.
AB  - A case of successful and prolonged treatment of metastatic non-small cell lung
      cancer with the epidermal growth factor receptor antagonist erlotinib is
      presented. A never-smoker female was diagnosed with stage IV lung cancer in
      December 2005. A chest CT scan showed soft tissue mass 35*34 mm in size in the
      right lung with metastases in the lymph nodes and in the left lung. A biopsy
      revealed a poorly differentiated adenocarcinoma. The disease showed poor response
      to the first-line and second-line chemotherapy. Targeted therapy with erlotinib
      was started in February 2007. The most severe adverse event observed was grade 3
      skin rash. The disease was stable until February 2009 when brain metastases were
      detected. Erlotinib was continued until May 2009 when disease progression in the
      lungs was confirmed. The patient died due to ongoing disease progression in
      December 2009. Retrospective genetic analysis of a tumor specimen was performed,
      and no mutations in EGFR exons 18-21 were detected. The patient had a significant
      clinical benefit for the period of 24 months. These results are consistent with
      previous reports in literature that clinical characteristics such as female
      gender, nonsmoker, adenocarcinoma histology, and severe cutaneous toxicity seem
      to predict good response to erlotinib. In the present case, erlotinib proved to
      be effective even in heavily pretreated, chemotherapy-resistant lung
      adenocarcinoma. So far, no exact predictive biomarkers of erlotinib effectiveness
      have been determined; and their further analyses are essential.

PMID- 22156605
TI  - Cardiovascular magnetic resonance for visualization of myocardial ischemia at
      rest.
AB  - This article presents the case of a 54-year-old male with evidence of myocardial
      ischemia at rest. In our case, by means of cardiovascular magnetic resonance,
      myocardial ischemia at rest in theoretical left anterior descending artery
      territory was proved, myocardial scar was excluded, and need for
      revascularization was validated.

PMID- 22156606
TI  - Stroke mortality trends in the population of Klaipeda from 1994 to 2008.
AB  - The objective of the study was to evaluate the trends in stroke mortality in the
      population of Klaipeda aged 35-79 years from 1994 to 2008. MATERIAL AND METHODS:
      Mortality data on all permanent residents of Klaipeda aged 35-79 years who died
      from stroke in 1994-2008 were gathered for the study. All death certificates of
      permanent residents of Klaipeda aged 35-79 years who died during 1994-2008 were
      examined in this study. The International Classification of Diseases (ICD-9 codes
      430-436, and ICD-10 codes I60-I64) was used. Sex-specific mortality rates were
      standardized according to the Segi's world population; all the mortality rates
      were calculated per 100 000 population per year. Trends in stroke mortality were
      estimated using log-linear regression models. Sex-specific mortality rates and
      trends were calculated for 3 age groups (35-79, 35-64, and 65-79 years). RESULTS:
      During the entire study period (1994-2008), a marked decline in stroke mortality
      with a clear slowdown after 2002 was observed. The average annual percent changes
      in mortality rates for men and women aged 35-79 years were -4.6% (P=0.041) and 
      6.5% (P=0.002), respectively. From 1994 to 2002, the stroke mortality rate
      decreased consistently among both Klaipeda men and women aged 35-64 years (20.4%
      per year, P=0.002, and 14.7% per year, P=0.006, respectively) and in the elderly
      population aged 65-79 years (13.8% per year, P=0.005; and 12% per year, P=0.019).
      During 2003-2008, stroke mortality increased by 16.3% per year in middle-aged men
      (35-64 years), whereas among women (aged 35-64 and 65-79 years) and elderly men
      (aged 65-79 years), the age-adjusted mortality rate remained relatively
      unchanged. CONCLUSIONS: Among both men and women, the mortality rates from stroke
      sharply declined between 1994 and 2008 with a clear slowdown in the decline after
      2002. Stroke mortality increased significantly among middle-aged men from 2003,
      while it remained without significant changes among women of the same age and
      both elderly men and women.

PMID- 22156607
TI  - Contact sensitization to the allergens of European baseline series in patients
      with chronic leg ulcers.
AB  - BACKGROUND AND OBJECTIVE: The pattern of contact sensitization among patients
      with chronic leg ulcers depends on the local practice of wound treatment along
      with demographic and clinical confounders. The study was aimed at revealing the
      associations between chronic leg ulcers and contact sensitization. MATERIAL AND
      METHODS: Between 2006 and 2008, 35 patients with chronic leg ulcers and
      surrounding dermatitis and 59 patients with contact dermatitis of the lower leg
      or foot were prospectively recruited at the Department of Skin and Venereal
      Diseases, Lithuanian University of Health Sciences. Demographic and clinical data
      were collected in accordance with the "minimal data set" of the European
      Surveillance System on Contact Allergy. Patch testing was performed with the
      allergens of the European baseline series. RESULTS: At least one positive patch
      test reaction was found in 28 (80%) of the patients with chronic leg ulcers and
      in 24 (41%) of the patients with dermatitis of the lower leg or foot (P<0.001).
      Sensitization to some of the most common allergens, namely colophony, Myroxylon
      pereirae resin, and methyldibromo glutaronitrile, was prevalent in both the
      groups of patients, whereas sensitization to benzocaine, p-phenylenediamine, and
      lanolin alcohol was associated with the presence of chronic leg ulcers.
      Benzocaine was found to be the leading allergen among patients with chronic leg
      ulcers (positive patch test reactions in 34.4% of the patients). CONCLUSIONS:
      Contact sensitization to benzocaine, p-phenylenediamine, and lanolin was found to
      be associated with the presence of chronic leg ulcers.

PMID- 22156608
TI  - Curcumins promote monocytic gene expression related to beta-amyloid and
      superoxide dismutase clearance.
AB  - Neurodegenerative diseases are associated with accumulation of modified proteins
      or peptides including amyloid-beta (Abeta) in Alzheimer's disease (AD), and
      misfolded superoxide dismutase-1 (SOD-1) in amyotrophic lateral sclerosis (ALS).
      Clearance of Abeta or SOD-1 by the innate immune system may be important for
      controlling or preventing disease onset. Curcumins restore Abeta phagocytosis by
      peripheral blood mononuclear cells (PBMCs) from AD patients and Abeta clearance
      with upregulation of key genes including MGAT3, vitamin D receptor (VDR) and Toll
      like receptors (TLRs). Certain curcumins inhibit inflammatory processes of PBMCs
      from ALS patients. We developed an in vitro system using human monocytes from
      patients and monocytic cell lines (i.e. U-937, THP-1) for evaluating curcuminoid
      potency of innate immune cell stimulation. Bisdemethoxycurcumin and certain
      analogs potentiated MGAT3,VDR and TLR gene expression 3- to 300-fold in U-937
      cells. The effect of curcumins on inflammation in monocytes from patients with
      ALS was examined. Recursive medicinal chemistry was applied to identify compounds
      that stimulate the innate immune system for use in the clearance of Abeta in AD
      and the reversal of neuroinflammation and defective SOD-1 accumulation in ALS.

PMID- 22156609
TI  - Correlation of cough with disease activity and treatment with cyclophosphamide in
      scleroderma interstitial lung disease: findings from the Scleroderma Lung Study.
AB  - BACKGROUND: Cough is a significant symptom in patients with scleroderma
      interstitial lung disease (SSc-ILD), affecting 73% of the 158 patients enrolled
      in the Scleroderma Lung Study (SLS), a multicenter randomized trial of oral
      cyclophosphamide (CYC) vs placebo (PLA) in patients with active interstitial lung
      disease. METHODS: We examined the correlation of cough frequency and severity and
      phlegm production at baseline in 156 SLS participants with other baseline
      variables representing SSc-ILD disease activity and the cough response to 1 year
      of treatment with CYC vs PLA. RESULTS: Patients with cough at baseline had
      significantly lower diffusing capacity of the lung for carbon monoxide, dyspnea,
      the quality-of-life physical component summary, and the maximal fibrosis score on
      high-resolution CT imaging compared with those without cough at baseline. Cough
      severity and frequency correlated with FVC % predicted. After 12 months of
      treatment, cough frequency decreased in the CYC group compared with the PLA group
      and was significantly different from the PLA group at 18 months (6 months after
      discontinuation of CYC). However, the decreases in cough frequency did not
      correlate with the changes in FVC or diffusing capacity of the lung for carbon
      monoxide observed in the CYC group. Treatment-related improvements in cough
      frequency, as well as in FVC, were no longer apparent 12 months after
      discontinuation of CYC. CONCLUSIONS: Cough is a common symptom in SSc-ILD and
      correlates with the extent of fibrosis. Cough frequency decreases significantly
      in response to treatment with CYC but returns to baseline 1 year after withdrawal
      of treatment. Cough may be a symptom of ongoing fibrosis and an independent
      variable in assessing therapeutic response to CYC. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT000004563; URL: www.clinicaltrials.gov

PMID- 22156610
TI  - Randomized clinical trial of endobronchial ultrasound needle biopsy with and
      without aspiration.
AB  - BACKGROUND: Endobronchial ultrasound (EBUS)-guided transbronchial needle
      aspiration (EBUS-TBNA) is performed with a dedicated 22- or 21-gauge needle while
      suction is applied. Fine-needle sampling without suction (capillary sampling) has
      been studied for endoscopic ultrasound and for biopsies at various body sites and
      has resulted in similar diagnostic yield and fewer traumatic samples. However,
      the role of EBUS-guided transbronchial needle capillary sampling (EBUS-TBNCS) is
      still to be determined. METHODS: Adults with suspicious hilar or mediastinal
      lymph nodes (LNs) were included in a single-blinded, prospective, randomized
      trial comparing EBUS-TBNA and EBUS-TBNCS. The primary end point was the
      concordance rate between the two techniques in terms of adequacy and diagnosis of
      cytologic samples. The secondary end point was the concordance rate between the
      two techniques in terms of quality of samples. RESULTS: A total of 115 patients
      and 192 LNs were studied. Concordance between EBUS-TBNA and EBUS-TBNCS was high,
      with no significant difference in adequacy (88% vs 88%, respectively [P +/-
      .858]; concordance rate, 83.9% [95% CI, 77.9-88.8]); diagnosis (36% vs 34%,
      respectively [P +/- .289]; concordance rate, 95.8% [95% CI, 92-92.8]); diagnosis
      of malignancy (28% vs 26%, respectively [P +/- .125]; concordance rate, 97.9%
      [95% CI, 94.8-99.4]); or sample quality (concordance rate, 83.3% [95% CI, 73.3
      88.3]). Concordance between EBUS-TBNA and EBUS-TBNCS was high irrespective of LN
      size (<= 1 cm vs > 1 cm). CONCLUSIONS: Regardless of LN size, no differences in
      adequacy, diagnosis, or quality were found between samples obtained using EBUS
      TBNA and those obtained using EBUS-TBNCS. There is no evidence of any benefit
      derived from the practice of applying suction to EBUS-guided biopsies. TRIAL
      REGISTRY: ClinicalTrials.gov; No.: NCT00886847; URL: www.clinicaltrials.gov

PMID- 22156611
TI  - Clinical effects of adjuvant active specific immunotherapy differ between
      patients with microsatellite-stable and microsatellite-instable colon cancer.
AB  - PURPOSE: Active specific immunotherapy (ASI) consisting of an autologous tumor
      cell vaccine given as adjuvant treatment has been shown to improve recurrence
      free survival of patients with colon cancer. The aim of the current retrospective
      study was to investigate whether the beneficial effects of ASI given as adjuvant
      treatment correlated with microsatellite instability (MSI), which is considered
      an important biologic determinant of colon cancer. EXPERIMENTAL DESIGN:
      Microsatellite status was assessed on archival tumor material from patients with
      stage II and III colon cancer. Microsatellite status was next associated with
      clinical outcome in control and ASI treatment groups using Kaplan-Meier analysis.
      RESULTS: We identified 162 (83%) microsatellite-stable tumors (MSS) and 34 (17%)
      MSI tumors. Patients with MSI tumors did well in recurrence-free interval (RFI)
      as well as disease-specific survival (DSS) irrespective of treatment arm and
      tumor stage. Patients with MSI tumors had significantly fewer recurrences and
      prolonged DSS than those with MSS tumors. Patients with MSS Dukes B tumors who
      received ASI treatment showed a significantly improved recurrence-free survival
      compared with controls. ASI treatment did not improve recurrence-free interval or
      DSS for patients with MSS Dukes C tumors. CONCLUSION: This retrospective study
      indicated that patients with MSI tumors did well, irrespective of treatment arm
      and tumor stage. The data also indicate that the clinical benefit, measured as
      recurrence-free survival, from adjuvant ASI treatment of patients with colon
      cancer was restricted to patients with MSS Dukes B tumors.

PMID- 22156612
TI  - Modeling a lethal prostate cancer variant with small-cell carcinoma features.
AB  - PURPOSE: Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct
      clinical behavior, resistance to androgen ablation, and frequent but short
      responses to chemotherapy. We sought to develop model systems that reflect human
      SCPC and can improve our understanding of its biology. EXPERIMENTAL DESIGN: We
      developed a set of castration-resistant prostate carcinomas xenografts and
      examined their fidelity to their human tumors of origin. We compared the
      expression and genomic profiles of SCPC and large-cell neuroendocrine carcinoma
      (LCNEC) xenografts to those of typical prostate adenocarcinoma xenografts.
      Results were validated immunohistochemically in a panel of 60 human tumors.
      RESULTS: The reported SCPC and LCNEC xenografts retain high fidelity to their
      human tumors of origin and are characterized by a marked upregulation of UBE2C
      and other mitotic genes in the absence of androgen receptor (AR), retinoblastoma
      (RB1), and cyclin D1 (CCND1) expression. We confirmed these findings in a panel
      of samples of CRPC patients. In addition, array comparative genomic hybridization
      of the xenografts showed that the SCPC/LCNEC tumors display more copy number
      variations than the adenocarcinoma counterparts. Amplification of the UBE2C locus
      and microdeletions of RB1 were present in a subset, but none displayed AR nor
      CCND1 deletions. The AR, RB1, and CCND1 promoters showed no CpG methylation in
      the SCPC xenografts. CONCLUSION: Modeling human prostate carcinoma with
      xenografts allows in-depth and detailed studies of its underlying biology. The
      detailed clinical annotation of the donor tumors enables associations of
      anticipated relevance to be made. Future studies in the xenografts will address
      the functional significance of the findings.

PMID- 22156613
TI  - Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic
      melanoma.
AB  - PURPOSE: To evaluate the effects of treatment with the potent mutant BRAF
      inhibitors GSK2118436 or vemurafenib (PLX4720) on immune responses to metastatic
      melanoma in tissues taken before and after treatment. EXPERIMENTAL DESIGN: Thirty
      seven tumor biopsies were collected from 15 patients with unresectable American
      Joint Committee on Cancer stage III or IV melanoma immediately before and
      approximately 7 days after the commencement of BRAF inhibitor treatment and at
      the time of tumor progression. Immunohistochemical staining was carried out on
      the biopsies using specific antibodies for CD8, CD4, CD20, CD1a, and Granzyme B.
      RESULTS: Tumor infiltration by CD4(+) and CD8(+) lymphocytes increased markedly
      following BRAF inhibitor treatment (both rho = 0.015). There was a correlation
      between the degree of tumor infiltration by CD8(+) and Granzyme B-expressing
      lymphocytes in post-BRAF inhibitor-treated biopsies (r = 0.690 and rho = 0.013).
      Increased intratumoral CD8(+) lymphocyte expression was correlated with a
      reduction in tumor size and an increase in necrosis in posttreatment biopsies (r
      = -0.793, rho = 0.011; and r = 0.761, rho = 0.004, respectively). CONCLUSIONS:
      The increase in tumor-infiltrating lymphocytes induced by treatment with BRAF
      inhibitors provides strong support for conducting trials that combine BRAF
      inhibitors with immunotherapy in the hope of prolonging clinical responses.

PMID- 22156614
TI  - A case of orthostatic tachycardia syndrome presenting with panic attack during
      tilt table testing.
AB  - A 26-year-old woman experienced syncope on standing 2-3 times a year for more
      than 15 years. The attack was typically associated with palpitations and
      frequently accompanied by a feeling of intense fear. The patient underwent head
      up tilt table testing at 70 degrees  for 40 min to determine the cause of the
      syncope. The tilt test results suggested that the etiology of the syncope was
      orthostatic tachycardia syndrome complicated by panic attack-associated
      hypocapnic hyperventilation, which presumably caused a greater degree of deep
      cerebral hypoperfusion than would be expected with orthostatic tachycardia
      syndrome alone, ultimately leading to the patient's symptoms, including syncope.
      In conclusion, monitoring the ventilation and/or arterial CO(2) level during head
      up tilt table testing is occasionally required when evaluating patients with
      postural syncope.

PMID- 22156616
TI  - Smoking and multiple sclerosis: a matter of global importance.

PMID- 22156615
TI  - Macrophages inhibit migration, metabolic activity and osteogenic differentiation
      of human mesenchymal stem cells in vitro.
AB  - To better elucidate the role of macrophages in bone morphogenetic protein (BMP)
      induced bone repair, this study evaluated the effects of macrophages on the
      migration, metabolic activity and BMP-2-induced osteogenic differentiation of
      human mesenchymal stem cells (hMSCs). Human monocytes were induced into a
      macrophage phenotype, and the conditioned media (CM) from undifferentiated
      monocytes and differentiated macrophages were collected for treatment of hMSCs.
      Expression levels of osteoblastic marker genes, alkaline phosphatase (ALP)
      activity and mineral deposition were assessed. The migration of hMSCs was
      significantly decreased after treatment with the macrophage CM (but not monocyte
      CM), in a dose-dependent manner. Significant inhibition of hMSC metabolism was
      observed on days 3 and 7 after treatment with the macrophage CM. The osteoblastic
      marker genes analyzed (ALP, bone sialoprotein, osteocalcin and runt-related
      transcription factor-2) after exposure of hMSCs to BMP-2 were all significantly
      downregulated in cells treated with the macrophage CM. The hMSCs treated with
      macrophage CM showed significantly decreased enzymatic activity of ALP and
      calcium content compared with those treated with monocyte CM or basal medium.
      High levels of interleukin-1beta and tumor necrosis factor-alpha found in
      macrophage CM may mediate these observed effects on hMSCs. We conclude that
      macrophage CM suppressed the BMP-2-induced osteogenic differentiation of hMSCs,
      suggesting that macrophages might contribute to decreased osteogenic effects of
      BMPs in a clinical setting.

PMID- 22156617
TI  - Gender-dependent bimanual task performance.
AB  - BACKGROUND AND OBJECTIVE: Many studies have suggested that each hand has a
      different special talent; however, there is a lack of data in the area of goal
      directed bimanual hand coordination and its dependence on gender. The aim of this
      paper was to investigate gender-dependent bimanual speed-accuracy task
      performance. MATERIAL AND METHODS: Twelve healthy young males and twelve healthy
      young females (all right-handed) performed protractile movements with both arms
      simultaneously by pushing joysticks toward two targets as quickly and accurately
      as possible. RESULTS: Though no significant difference was observed in the
      reaction time during a unimanual speed-accuracy task between the left and right
      hands as well as men and women, during a bimanual task, the reaction time of both
      the hands was significantly longer in women than men. There was no significant
      difference in the velocity of both the hands during a bimanual speed-accuracy
      task between men and women, while the accuracy of the left hand was significantly
      greater in men than women. There was no significant difference in intraindividual
      variability in the reaction time, maximal velocity, and path of movement between
      men and women as well as the left and right hands, but variability in the average
      velocity of the right hand both in women and men was significantly greater
      compared with their left hand. CONCLUSIONS: Whereas people typically look at the
      target location for a reaching movement, it is possible that two objects are
      simultaneously fixated.

PMID- 22156618
TI  - Effectiveness of the second-stage rehabilitation in stroke patients with
      cognitive impairment.
AB  - The aim of this study was to evaluate the recovery of functional status and
      effectiveness of the second-stage rehabilitation depending on the degree of
      cognitive impairment in stroke patients. MATERIAL AND METHODS: The study sample
      comprised 226 stroke patients at the Virsuziglis Hospital of rehabilitation,
      Hospital of Lithuanian University of Health Sciences. Functional status was
      evaluated with the Functional Independence Measure, cognitive function with the
      Mini-Mental Status Examination scale, and severity of neurologic condition with
      the National Institutes of Health Stroke Scale. The patients were divided into 4
      study groups based on cognitive impairment: severe, moderate, mild, or no
      impairment. RESULTS: More than half (53%) of all cases were found to have
      cognitive impairment, while patients with different degree of cognitive
      impairment were equally distributed: mild impairment (18%), moderate impairment
      (17%), and severe impairment (18%). Improvement of functional status was observed
      in all study groups (P<0.001). In the patients with moderate and severe cognitive
      impairment, cognitive recovery was significantly more expressed than in other
      study groups (P<0.001). Insufficient recovery of functional status was
      significantly associated with hemiplegia (OR, 11.15; P=0.015), urinary
      incontinence (OR, 14.91; P<0.001), joint diseases (OR, 5.52; P=0.022), heart
      diseases (OR, 4.10; P=0.041), and severe cognitive impairment (OR, 15.18;
      P<0.001), while moderate and mild cognitive impairment was not associated with
      the recovery of functional status. CONCLUSIONS: During the second-stage
      rehabilitation of stroke patients, functional status as well as cognitive and
      motor skills were improved both in patients with and without cognitive
      impairment; however, the patients who were diagnosed with severe or moderate
      cognitive impairment at the beginning of second-stage rehabilitation showed worse
      neurological and functional status during the whole second-stage rehabilitation
      than the patients with mild or no cognitive impairment.

PMID- 22156619
TI  - Tissue transglutaminase: a novel therapeutic target in cerebral amyloid
      angiopathy.
AB  - Accumulation of amyloid-beta (Abeta) in brain vessel walls, known as cerebral
      amyloid angiopathy (CAA), plays a key role in Alzheimer's disease pathogenesis.
      CAA might result from impaired transport of Abeta out of the brain. Although the
      mechanisms underlying reduced Abeta transport are largely unknown, thickening of
      basement membrane extracellular matrix (ECM) is likely involved. Tissue
      transglutaminase (tTG) is an enzyme capable of modulating the ECM by covalently
      cross-linking ECM proteins. Recently, our group found that tTG and its cross
      linking activity are associated with CAA pathology, suggesting a role for tTG in
      ECM modulation in CAA. Therefore, inhibition of tTG activity might be a promising
      novel therapeutic target to counteract CAA.

PMID- 22156620
TI  - How to manage left ventricular hypertrabeculation/noncompaction in Fabry's
      disease?

PMID- 22156621
TI  - Phase II open-label study of erlotinib in combination with gemcitabine in
      unresectable and/or metastatic adenocarcinoma of the pancreas: relationship
      between skin rash and survival (Pantar study).
AB  - BACKGROUND: Skin rash is an adverse event which might be associated with longer
      survival in patients treated with epidermal growth factor receptor tyrosine
      kinase inhibitors. The aim of this nonrandomised phase II clinical trial is to
      prospectively evaluate the relationship between skin rash and overall survival
      (OS) in advanced/metastatic pancreatic cancer treated with erlotinib plus
      gemcitabine. PATIENTS AND METHODS: Patients were given gemcitabine (1000
      mg/m2/week, 3 weeks every 4 weeks) plus erlotinib (100 mg/day orally
      continuously) until disease progression/unacceptable toxicity. The primary end
      point was OS. RESULTS: A total of 153 eligible patients were enrolled (grade>=2
      rash, 25%; grade<2 rash, 75%). OS was longer in patients with grade>=2 rash
      versus grade<2 (11 versus 5 months; P<0.001). Progression-free survival was
      longer in patients with grade>=2 rash versus grade<2 (6 versus 3 months; P<0.001)
      and shorter in those without rash versus grade 1 (2 versus 4 months; P=0.005) or
      grade>=2 (2 versus 6 months; P<0.001). Patients with grade>=2 rash showed higher
      rates of overall response (21% versus 7%; P<0.05) and disease control (84% versus
      43%; P<0.05) versus grade<2. CONCLUSIONS: This study prospectively confirms the
      relationship between rash and longer OS in unresectable locally
      advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine.

PMID- 22156622
TI  - Relationship between LAPTM4B gene polymorphism and susceptibility of primary
      liver cancer.
AB  - BACKGROUND: Lysosome associated protein transmembrane 4 beta (LAPTM4B) was
      identified first as a novel gene overexpressed in human hepatocellular carcinoma.
      LAPTM4B*1 and LAPTM4B*2 are two alleles of the gene; they are differentiated at
      5'UTR in the first exon. Allele *1 contains only one copy of a 19-bp sequence in
      the 5'UTR. However, allele *2 contains another identical 19-bp sequence following
      the first one tightly. In this case-control study, we aimed to identify the
      relationship between LAPTM4B gene polymorphism and the susceptibility of primary
      liver cancer. MATERIALS AND METHODS: The case-control study was conducted in
      China, including 303 primary liver cancer cases and 515 controls. LAPTM4B gene
      polymorphism was determined by PCR. Statistical analysis includes odds ratio (OR)
      and 95% confidence interval (CI) calculations using unconditional logistic
      regression. RESULTS: We found a significant difference in the frequency of
      LAPTM4B*2 between cases and controls (P<0.05). Our study showed that LAPTM4B*1/2
      and *2/2 were associated with a significantly increased risk of primary liver
      cancer compared with LAPTM4B*1/1 (OR=1.898, 95% CI=1.387-2.598 and OR=2.483, 95%
      CI=1.480-4.168, respectively). The genotypes of LAPTM4B in this study have
      negative correlation with the clinicopathologicals observed. CONCLUSION: The
      evidences suggest that gene polymorphism of LAPTM4B may influence the
      individuals' susceptibility to primary liver cancer and allele *2 being
      considered as a potential risk factor.

PMID- 22156623
TI  - Screening mammography and socioeconomic inequalities in breast cancer survival.

PMID- 22156624
TI  - Updated survival and outcomes for older adults with inoperable stage III non
      small-cell lung cancer treated with cisplatin, etoposide, and concurrent chest
      radiation with or without consolidation docetaxel: analysis of a phase III trial
      from the Hoosier Oncology Group (HOG) and US Oncology.
AB  - BACKGROUND: Concurrent chemoradiation with etoposide and cisplatin (EP/XRT) is
      standard treatment for inoperable stage III locally advanced non-small-cell lung
      cancer (LA-NSCLC). Consolidation docetaxel (D; Taxotere) after EP/XRT resulted in
      increased toxicity but no improvement in survival compared with observation (O).
      We report updated survival for the entire study population and include an
      analysis of efficacy and tolerability of EP/XRT with or without D in patients
      aged >= 70 years. PATIENTS AND METHODS: Hoosier Oncology Group LUN 01-24 enrolled
      243 patients with LA-NSCLC and randomized 166 after EP/XRT to three cycles of D
      versus O. the trial was terminated after an analysis of the first 203 patients
      demonstrated futility of D. RESULTS: Median survival time (MST) for the overall
      study population was 21.5 months, and 3-, 4-, and 5-year survival rates were
      30.7%, 18.0%, and 13.9%, respectively. No differences in MST or 3-year survival
      were noted between D and O arms. Older patients had similar MST (17.1 versus 22.8
      months for younger patients, P = 0.15) but higher rates of grade 3/4 toxicity and
      hospitalization during induction. CONCLUSIONS: Consolidation docetaxel after
      EP/XRT does not improve survival in LA-NSCLC. Fit older adults with LA-NSCLC
      benefit from concurrent chemoradiation similarly as younger patients but
      experience higher rates of hospitalization and toxicity.

PMID- 22156625
TI  - Post-stroke carotid ultrasound findings from an incident Tanzanian population.
AB  - BACKGROUND: Carotid artery stenosis is not thought to be a major cause of stroke
      in sub-Saharan Africa, though data are limited. The aim of this study was to use
      Duplex ultrasonography to establish the prevalence of significant carotid artery
      stenosis in an incident stroke population in Tanzania. METHODS: Duplex ultrasound
      scan was carried out on consecutive cases of stroke, in the latter part of a
      stroke incidence study, who survived long enough to undergo investigation. As
      part of the wider incidence study, demographic data, social history, medical
      history, levels of current disability and findings from computer tomography scan
      and electrocardiogram were recorded. RESULTS: 132 incident stroke cases were
      identified over the whole study period, of whom 56 (42.4%) underwent Duplex
      ultrasound. Only 1 case (female, aged 56 years) had evidence of right internal
      carotid artery stenosis, with a mild degree of stenosis of around 50%. There was
      no evidence of stenosis of either common carotid artery or of the left internal
      carotid artery in any cases. CONCLUSIONS: Carotid artery stenosis was rare in our
      cohort and does not appear to be a significant cause of stroke in our incident
      cohort.

PMID- 22156626
TI  - Electron microscopy analysis of neurites extending from dorsal root ganglia in
      vitro following exposure to intervertebral disc cells.
AB  - Nucleus pulposus cells from the intervertebral disc have been shown to have
      inhibiting effects on neurite outgrowth in vitro. The nucleus pulposus consists
      of at least 2 cell populations, notochordal cells and chondrocyte-like cells. The
      aim of this study was to analyze the morphology of the neurites, from rat dorsal
      root ganglia (DRG) in a culture system, after exposure of these 2 cell
      populations. DRG from perinatal rats was harvested and placed in culture dishes
      for 24 h. Nucleus pulposus cells from donor rats were separated into 2
      populations and applied to the DRG and neurite culture for a further 24 h and
      compared to control cultures exposed to culture medium without cells. The DRG and
      neurites were thereafter prepared for scanning or transmission electron
      microscopy (SEM/TEM). Descriptive SEM and TEM analyses and calculations of the
      neurite diameter were performed. The visual appearance after SEM and TEM
      preparation was similar in the three different culture conditions. However, there
      was a statistically significant reduction of the neurite diameter for the
      cultures exposed to notochordal cells compared to the cultures exposed to medium
      and chondrocyte-like cells (TEM preparation). Prominent and frequent pathologic
      abnormalities in peripheral nerve diseases have been observed with changes in
      axonal caliber. This study may suggest that a preserved small amount of
      notochordal cells, as seen in human adults, may play a role in clinical
      situations where nerve tissue is exposed to disc material, i.e. in disc
      herniation or degeneration.

PMID- 22156627
TI  - The texture of neighborhoods and disability among older adults.
AB  - OBJECTIVES: To present and test an ecological multidimensional model of
      neighborhood characteristics and examine its relationship to older disability
      among older adults. METHOD: Indicators of social vulnerability, wealth, violence,
      storefronts, residential stability, and the presence of physicians, supermarkets,
      and fast-food establishments for 1,644 of New Jersey's census tracts were derived
      from sources that include the U.S. Census 2000, Uniform Crime Report for New
      Jersey, New Jersey Department of Agriculture, Division of Marketing and
      Development, New Jersey Department of Law and Public Safety Division of Alcohol
      Beverage Control, and Health Resources and Services Administration Geospatial
      Data Warehouse. Confirmatory factor analyses were used to develop and test a
      measurement model of neighborhood texture. Structural equation modeling examined
      the relationships between neighborhood characteristics and disability of persons
      aged 65-69 years. RESULTS: Analyses revealed that distinct dimensions of
      neighborhoods could be modeled with administrative data and that neighborhood
      contextual (supermarkets, physicians, storefronts, violence) and compositional
      (social vulnerability, wealth, residential stability) characteristics were
      related to the prevalence of disability. DISCUSSION: The use of multiple
      indicators of neighborhood with good psychometric qualities is critical for
      advancing knowledge about the mechanisms by which neighborhood characteristics
      are associated with the health of older people.

PMID- 22156628
TI  - Coverage or costs: the role of health insurance in labor market reentry among
      early retirees.
AB  - OBJECTIVES: This study evaluated the impact of insurance coverage on the odds of
      returning to work after early retirement and the change in insurance coverage
      after returning to work. METHOD: The Health and Retirement Study was used to
      estimate hierarchical linear models of transitions to full-time work and part
      time work relative to remaining retired. A chi-square test was also used to
      assess change in insurance coverage after returning to work. RESULTS: Insurance
      coverage was unrelated to the odds of transitioning to full-time work. However,
      relative to employer-provided insurance, private nongroup insurance increased the
      odds of transitioning to part-time work, whereas public insurance reduced the
      odds of making this transition. Additionally, after returning to work, insurance
      coverage increased among those who were without employer-provided insurance in
      retirement. DISCUSSION: Results indicated that source of coverage may be more
      useful in explaining returns to part-time work than simply whether people have
      coverage at all. In other words, the mechanism underlying the positive
      relationship between insurance and returning to work appeared to be limited to
      those who return to work because of the cost of private nongroup insurance. Among
      these people, however, there was some evidence that they are able to secure new
      coverage once they return to work.

PMID- 22156629
TI  - Forgiveness of others and health: do race and neighborhood matter?
AB  - OBJECTIVES: This study examines the relationship between interpersonal
      forgiveness and health for older Blacks and Whites. We outline a series of
      arguments concerning the following: (a) how forgiveness can affect health, (b)
      how forgiveness may be more protective for Blacks, and (c) how the relationship
      between forgiveness and health may vary by neighborhood deterioration. METHOD:
      Two waves (2001 and 2004) of the Religion, Aging, and Health Survey provided data
      from a nationally representative elderly sample of 436 Blacks and 500 Whites.
      Measures included sociodemographics, forgiveness, and three dimensions of health:
      self-reported health, alcohol use, and chronic conditions. We employ both
      longitudinal and cross-sectional analyses. RESULTS: Results suggest that
      forgiveness of others was protective of health for Blacks but not Whites.
      Moreover, among Blacks, we found the following: (a) forgiveness was positively
      associated with self-reported health over time, (b) forgiveness was negatively
      associated with alcohol use and number of chronic conditions, and (c) forgiveness
      interacted with neighborhood deterioration such that the beneficial effects of
      forgiveness for self-reported health did not extend to those living in run-down
      neighborhoods. DISCUSSION: Race and neighborhood were shown to be important for
      understanding the forgiveness-health connection. Forgiveness was associated with
      better health for Blacks but not Whites, consistent with McCullough's
      evolutionary framework (McCullough, M. E. (2008). Beyond revenge: The evolution
      of the forgiveness instinct. San Francisco, CA: Jossey-Bass), forgiveness was
      beneficial in some settings but had a deleterious impact in more noxious
      environments. This study suggests that researchers should give more consideration
      to race and social context in attempting to more fully understand the
      relationship between forgiveness and health.

PMID- 22156630
TI  - The health implications of grandparents caring for grandchildren in China.
AB  - OBJECTIVES: Caring for grandchildren is a common and normative experience for
      many Chinese grandparents. This study investigates the influence of child care
      provision on older adults' health trajectories in China. METHOD: Using data from
      the China Health and Nutrition Survey (1991, 1993, 1997, 2000, 2004, and 2006),
      we apply growth curve models to examine the effect of living arrangements and
      intensity of caregiving for grandchildren on older adults' health trajectories.
      We use propensity score weighting to take into account potential selection bias.
      RESULTS: Grandparents living in skipped-generation households do not suffer from
      a deficit in self-reported health, particularly when they have higher family
      income. Those living in three-generation households experience a slightly more
      rapid health decline than older adults who live independently, although the
      paternal grandparents in this type of household have a significant health
      advantage over the maternal grandparents. Among the coresiding grandparents, high
      intensity care for younger grandchildren accelerates health declines, whereas a
      lighter level of care has a protective effect. In addition, rural grandparents
      and grandfathers engaging in high intensity care have worse self-reported health
      on average. DISCUSSION: Our findings suggest that grandchild care does not have a
      universally beneficial or detrimental effect on health, but rather its effect
      depends on the form and level of caregiving and is further shaped by individual
      characteristics, as well as normative and structural contexts.

PMID- 22156631
TI  - The immunoprotective role of interleukin-10 in abnormal pregnancy outcome induced
      by Toxoplasma gondii infection.
AB  - AIMS: To investigate the immunoprotective effect of IL-10 on pregnancy in
      Toxoplasma gondii-infected C57BL/6 mice. METHODS: Twenty-four pregnant mice were
      randomly divided into 3 equal groups, i.e. a control group (CG), an infected
      group (IG) and an infected group treated with IL-10 (IPTG). Each IPTG and IG
      mouse was infected with 400 T. gondii trophozoites on gestational day (GD) 8.
      Each IPTG mouse was injected with 1 MUg recombinant mouse IL-10 via a tail vein
      on GD 10 and 12. The mice were sacrificed on day 7 postinfection. Qa-1 and NKG2A
      were analyzed in the placenta by flow cytometry and real-time PCR. IL-4, IL-10
      and IFN-gamma in the placenta supernatant were analyzed by ELISA. Statistical
      analysis was performed by one-way ANOVA. RESULTS: IPTG mice showed a better
      mental state, had larger fetuses and placentas with a better blood supply and a
      lower resorption ratio compared to IG mice. NKG2A and Qa-1 were significantly
      increased in IPTG mice compared to IG mice (p < 0.05). IL-4 and IL-10 in IPTG
      placenta supernatant were increased (p < 0.05), but IFN-gamma was decreased (p <
      0.05) compared to IG placenta supernatant. The ratios of IFN-gamma/IL-4 and IFN
      gamma/IL-10 were decreased in IPTG mice compared to IG mice (p < 0.05, p < 0.05).
      CONCLUSION: IL-10 plays an immunoprotective role and improves the pregnancy
      outcome of T. gondii-infected mice.

PMID- 22156632
TI  - Bacille Calmette-Guerin vaccination in Saudi Arabia: benefits versus risks.

PMID- 22156633
TI  - Outbreak of Bacille Calmette-Guerin-related lymphadenitis in Saudi children at a
      university hospital after a change in the strain of vaccine.
AB  - BACKGROUND AND OBJECTIVES: Bacille Calmette-Guerin (BCG) vaccination is part of
      the expanded program of vaccination in Saudi Arabia. Lymphadenitis is the most
      common complication of the BCG vaccine. We observed an increase in the rate of
      BCG lymphadenitis that coincided with the introduction of a new strain of BCG
      vaccine. The aim of this study was to determine the incidence and the possible
      causes of BCG lymphadenitis at a university hospital in Riyadh, Saudi Arabia.
      DESIGN AND SETTING: Retrospective chart review and prospective follow up of
      infants who received BCG vaccine. METHODS: We studied all infants presenting with
      suppurative or nonsuppurative adenopathy with nodes age;2 cm seen at the
      infectious diseases clinic at KKUH. The study duration was divided into two
      periods. The first period reviewed infants who received different BCG vaccine
      strains between January 2002 and December 2007. The second study period was
      conducted after close evaluation of the BCG administration technique of the
      vaccinating staff and reviewed infants who received the BCG SSI Danish strain
      1331 between January 2008 and December 2010. RESULTS: During the study period
      from January 2002 to December 2007, 19 402 infants received four different BCG
      vaccine strains. Eight infants developed BCG lymphadenitis, and all were
      associated with the BCG SSI vaccine. The incidence rate in 2007 was 1.96 per
      1000. In the second period, 66 of 9921 infants who received the BCG SSI vaccine
      developed BCG lymphadenitis between January 2008 and December 2010. The incidence
      rate was 10.14 per 1000 in 2010. CONCLUSION: We conclude that receipt of the BCG
      SSI vaccine might have contributed to the increased incidence of lymphadenitis in
      these children. Hence, caution should be exercised in switching from one vaccine
      to another, as is often done in developing countries.

PMID- 22156635
TI  - Exploratory factor analytical study of depressive symptomatology: an Arab
      experience with a sample comprising college students, using the revised Beck
      Depression Inventory.
AB  - BACKGROUND AND OBJECTIVES: An understanding of the domains of depressive
      symptomatology could facilitate valid and interpretable comparisons across
      cultures. The objective of the present study was to assess the factor structure
      of the Beck Depression Inventory-II (BDI-II) in an Arab sample comprising college
      students, in comparison to the international data. DESIGN AND SETTING: Cross
      sectional questionnaire survey of Arab college students in their classrooms over
      a 1-year period. PATIENTS AND METHODS: Participants (n=624) who completed the
      questionnaire, which had been translated into Arabic, during the 2007-2008
      academic session. Exploratory factor analysis was done by principal axis
      factoring with oblique rotation. RESULTS: Factor 1 consisted of psychological
      symptoms. Factor 2 mainly comprised somatic symptoms, but with some affective
      symptoms (loss of interest, irritability). Factor 3 also belonged to a purely
      psychological domain, whereas factor 4 was another mixture of somatic and
      psychological symptoms (41.8% of variance explained). Thus the four domains were
      as follows: cognitive I, somatic-affective I, cognitive II, and somatic-affective
      II. These domains were similar in construct to the original subscales on which
      the BDI-II was validated for students in North America. Our four-factor solution
      fulfilled the recommended criteria, namely, a strong first factor, simple
      structure (parsimony), and stable factors with construct meanings that are in
      line with theory. CONCLUSION: Our factor structure defined depression in a manner
      consistent with theory, in that sadness, self-dislike, and guilt feelings defined
      the cognitive domain. whereas irritability and changes in sleep pattern and
      appetite mostly defined the somatic-affective domain. The BDI-II has construct
      validity across cultures.

PMID- 22156636
TI  - Evaluation of adjuvant therapy in women with uterine papillary serous cancer.
AB  - BACKGROUND AND OBJECTIVE: Uterine papillary serous cancer (UPSC) represents only
      10% of all uterine cancers and is associated with a significantly worse prognosis
      compared with other histological types of endometrial cancers. It closely
      resembles the behavior of ovarian carcinoma. DESIGN AND SETTING: Retrospective
      study in a referral center covering period from February 1989 to January 2009.
      PATIENTS AND METHODS: Eighteen patients who underwent definitive surgery followed
      by adjuvant therapy-platinum-based chemotherapy, radiotherapy, or both-were
      reviewed. Median age was 62 years (range, 52-76 years). All patients underwent
      total abdominal hysterectomy and salpingo-oophorectomy. Positive lymph nodes were
      found in 4 of 7 patients who underwent lymph node sampling/dissection. Seven
      patients had stage I/II disease, whereas 11 patients had stage III disease. Six
      patients received chemotherapy, 5 patients received radiation therapy, while 7
      patients received both chemotherapy and radiation therapy. RESULT: Median follow
      up was 27 months. The median survival and relapse-free survival were 33 and 23
      months, respectively. Eight patients were alive and free of disease, of whom 5
      patients were stage I/II and 4 patients were stage III. Distant metastasis was
      the most common site of relapse. Early stage (I/II) was associated with
      significant improvement in relapse-free survival (RFS) and overall survival (OS)
      (P=.004 and P=.05, respectively). The combined-modality treatment including
      chemotherapy-radiotherapy showed statistically significant improvement in RFS
      (P=.012), while the improvement in OS did not reach statistical significance
      (P=.12). CONCLUSION: This study indicates that postoperative combined treatment
      with chemotherapy and radiation therapy plays a role in the management of UPSC by
      improving RFS. Distant metastasis remains the major site of relapse. Future
      studies using combined-modality therapy are needed to improve the outcome in
      patients with UPSC.

PMID- 22156634
TI  - Baseline characteristics, management practices, and long-term outcomes of Middle
      Eastern patients in the Second Gulf Registry of Acute Coronary Events (Gulf RACE
      2).
AB  - BACKGROUND AND OBJECTIVES: Limited data are available on patients with acute
      coronary syndromes (ACS) and their long-term outcomes in the Arabian Gulf
      countries. We evaluated the clinical features, management, in-hospital, and long
      term outcomes of in such a population. DESIGN AND SETTING: A 9-month prospective,
      multicenter study conducted in 65 hospitals from 6 countries that also included
      30 day and 1-year mortality follow-up. PATIENTS AND METHODS: ACS patients
      included those with ST-elevation myocardial infarction (STEMI) and non-ST
      elevation acute coronary syndrome (NSTEACS), including non-STEMI and unstable
      angina. The registry collected the data prospectively. RESULTS: Between October
      2008 and June 2009, 7930 patients were enrolled. The mean age (standard
      deviation), 56 (17) years; 78.8% men; 71.2% Gulf citizens; 50.1% with central
      obesity; and 45.6% with STEMI. A history of diabetes mellitus was present in
      39.5%, hypertension in 47.2%, and hyperlipidemia in 32.7%, and 35.7% were current
      smokers. The median time from symptom onset to hospital arrival for STEMI
      patients was 178 minutes (interquartile range, 210 minutes); 22.3% had primary
      percutaneous coronary intervention (PCI) and 65.7% thrombolytic therapy, with 34%
      receiving therapy within 30 minutes of arrival. Evidence-based medication rates
      upon hospital discharge were 68% to 95%. The in-hospital PCI was done in 21% and
      the coronary artery bypass graft surgery in 2.9%. The in-hospital mortality was
      4.6%, at 30 days the mortality was 7.2% , and at 1 year after hospital discharge
      the mortality was 9.4% ; 1-year mortality was higher in STEMI (11.5%) than in
      NSTEACS patients (7.7%; P<.001). CONCLUSIONS: Compared to developed countries,
      ACS patients in Arabian Gulf countries present at a relatively young age and have
      higher rates of metabolic syndrome features. STEMI patients present late, and
      their acute management is poor. In-hospital evidence-based medication rates are
      high, but coronary revascularization procedures are low. Long-term mortality
      rates increased severalfold compared with in-hospital mortality.

PMID- 22156637
TI  - Eosinophilic pneumonia: experience at two tertiary care referral hospitals in
      Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Eosinophilic lung diseases are a diverse group of
      disorders characterized by pulmonary opacities associated with tissue or
      peripheral eosinophilia. DESIGN AND SETTING: A retrospective study conducted at
      two tertiary care hospitals from January 1999 to December 2009. METHODS: All
      cases with the diagnosis of pulmonary eosinophilia were reviewed over a period of
      10 years. Data on demographic, clinical, and radiologic characteristics were
      collected. RESULTS: Thirty-five patients with a mean age of 33.9 (16.2) years, of
      which 20 (57.1%) were male and meeting the criteria of eosinophilic lung disease
      were identified. Cough and dyspnea were the most frequent symptoms at
      presentation in 29 (82.9%) and 27 (77.1%) patients, respectively. Reticulonodular
      and airspace patterns were the most common radiographic findings in 17 (48.6%)
      and 15 (42.9%) patients, respectively. Peripheral eosinophilia was present in 33
      (94.3%) patients. Twenty-four patients (68.6%) were labeled as having idiopathic
      pulmonary infiltrate with eosinophilia. Complete remission was achieved in 13
      (54.2%) of 24 patients, while 10 (41.7%) patients relapsed within a few months of
      discontinuation of therapy. Specific therapy for a specific disease was
      administered in 8 patients: 2 patients for pulmonary tuberculosis, 2 for Churg
      Strauss syndrome, 1 for lymphoma, 1 for schistosomiasis, 1 for acute eosinophilic
      pneumonia, and 1 for Wegener granuloma; 3 patients were treated as allergic
      bronchopulmonary aspergillosis. CONCLUSIONS: Pulmonary eosinophilia remains rare
      but challenging, and it can have the same diverse clinical and radiographic
      presentations seen with other common pulmonary conditions. Clinicians should be
      alert to these syndromes and must think of them in any lung disease differential
      diagnoses.

PMID- 22156638
TI  - Serum uric acid and lactate levels among patients with obstructive sleep apnea
      syndrome: which is a better marker of hypoxemia?
AB  - BACKGROUND AND OBJECTIVES: Tissue hypoxia due to repeated sleep apneas leads to
      increased serum levels of uric acid (UA) and lactate in patients with obstructive
      sleep apnea syndrome (OSAS). Studies on assessment of serum level of UA in
      patients of OSAS are available. However, research on simultaneous evaluation of
      levels of serum lactate and UA is lacking. DESIGN AND SETTING: Prospective, case
      control study in a tertiary care institution. PATIENTS AND METHODS: Forty
      patients suffering from OSAS, diagnosed by night polysomnography (PSG), were
      included in this study. Forty age- and sex-matched subjects in whom the presence
      of OSAS was ruled out by night PSG were included as healthy controls.
      Participants underwent a procedure for the measurement of serum UA and lactate
      before and after sleep. RESULTS: Both before and after sleep UA levels of
      patients with OSAS were found to be significantly higher (P=.001 and .002,
      respectively) as compared to UA levels of controls.  A statistically significant
      (P=.02) overnight (after sleep) rise was observed in the serum lactate level of
      OSAS patients. The correlation between serum UA values and %TSTs (percentage of
      total sleep time spent) below 95% SaO2 (arterial oxygen saturation)  was
      statistically significant (P=.02). The correlation was positive with %TSTs below
      90% SaO2, whereas it was found negative with normal basal oxygen. No significant
      correlation was observed between serum UA and the AHI (apnea-hypopnea index).
      Polysomnographic variables failed to show significant correlation with serum UA
      on respective multiple regression models controlling for age, body mass index,
      and waist-hip ratio. However, plasma lactate levels after sleep correlated with
      %TSTs below 95% of SaO2 and AHI with P values of .02 and .01, respectively.
      CONCLUSIONS: Both serum UA and lactate were positively correlated with the degree
      of hypoxia in OSAS. The plasma UA levels in patients with OSAS did not show an
      overnight rise. However, the plasma lactate levels were higher in the morning.
      The measurement of serum lactate level was a better marker of oxidative stress
      among patients with OSAS.

PMID- 22156639
TI  - A retrospective review of autoinflammatory diseases in Saudi children at a
      rheumatology clinic.
AB  - BACKGROUND AND OBJECTIVE: Published data from Saudi Arabia regarding
      autoinflammatory diseases are scarce. In this study, we describe the clinical and
      laboratory features of autoinflammatory diseases in Saudi children. DESIGN AND
      SETTING: Restrospective, hospital-based study conducted from January 2010 until
      June 2010. PATIENTS AND METHODS: Patients with autoinflammatory disease treated
      at the Pediatric Rheumatology Clinic at King Faisal Specialist Hospital and
      Research Center, Riyadh, over the past 10 years were included. Autoinflammatory
      diseases included the following: familial Mediterranean fever (FMF); chronic
      recurrent multifocal osteomyelitis (CRMO); early-onset sarcoidosis (EOS);
      periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome
      (PFAPA); chronic infantile neurologic cutaneous and articular syndrome (CINCA);
      and Muckle-Wells syndrome (MWS). Demographic characteristics, diagnosis, age at
      onset, disease duration, follow-up duration, clinical and laboratory variables,
      and outcome data were compiled. Gathered laboratory data were part of patients'
      usual medical care. RESULTS: Thirty-four patients (females, 53%) with
      autoinflammatory diseases were included (mean age, 151 months). Mean disease
      duration was 118 months; mean age at onset was 32 months; consanguinity was
      present in 40%. Patients were diagnosed as follows: FMF, 50%; CRMO, 23.5%; CINCA,
      8.8%; EOS, 8.8%; MWS, 6%; and PFAPA, 2.9%. The referral diagnosis was inaccurate
      in all patients except for FMF patients. Gene study was informative in 9 of 14
      FMF patients who had molecular analyses. None of our cohort had amyloidosis. All
      CRMO patients had a favorable response to treatment except 1 patient, who had
      refractory, progressive disease. All patients with EOS had multiorgan
      involvement, including uveitis. All CINCA patients had a favorable response to
      anakinra. CONCLUSION: Our report shows that autoinflammatory diseases other than
      FMF may be overlooked. Increased awareness among pediatricians about these
      conditions will help to provide better health care to patients in the form of
      early diagnosis and management.

PMID- 22156640
TI  - Features associated with severe disease in hospitalized children with 2009
      influenza A (H1N1) infection at a university hospital in Riyadh, Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: In 2009, pandemic H1N1 influenza A caused significant
      morbidity and mortality worldwide; however, available data on disease
      characteristics and outcome of hospitalized children is limited. DESIGN AND
      SETTING: A prospective cohort study of children who required hospitalization
      because of the influenza A (H1N1) infection at King Khalid University Hospital in
      Riyadh, Saudi Arabia, over 6 months (July- December, 2009). PATIENTS AND METHODS:
      Data was collected using a predesigned form for all admitted pediatric cases (0
      12 years) presenting with the influenza-like illness and who tested positive for
      the novel influenza (H1N1) using reverse transcriptase polymerase chain reaction
      assay. The clinical course and features associated with the severe disease among
      such children were described RESULTS: Out of 1103 children with the influenza
      like illness, 375 (34%) were confirmed pediatric cases of influenza A (H1N1), of
      whom 50 (13.3%) required hospitalization. The median age was 3 years (range, 1
      month-12 years). Fever was the most frequent symptom (94%) at admission, followed
      by cough (86%) and other symptoms including vomiting and diarrhea. The majority
      (70%) of children had at least one underlying medical condition, with bronchial
      asthma being the most common (40%). All cases were treated with oseltamivir. Five
      children (10%) were admitted to the ICU, 4 required mechanical ventilation, and 2
      died (4%). CONCLUSIONS: The majority of children with 2009 H1N1 influenza A
      associated hospitalization in this series had an uncomplicated course.
      Respiratory complications and ICU admissions were more frequent in those with
      underlying disease, especially asthma and neuromuscular diseases. Efforts need to
      be focused prior to each influenza season and special emphasis needs to be given
      to children by immunizing them with H1N1 influenza A vaccination to avoid severe
      disease and minimize complications.

PMID- 22156641
TI  - Willingness of health care workers of various nationalities to accept H1N1 (2009)
      pandemic influenza A vaccination.
AB  - BACKGROUND AND OBJECTIVES: Media attention on 2009 H1N1 vaccination has been
      negative. Information on the willingness of health care workers (HCWs) to accept
      vaccination against the 2009 pandemic influenza is sparse. Thus, we undertook
      this study to investigate the attitude of HCWs toward this vaccine and possible
      factors associated with vaccine acceptance. DESIGN AND SETTING: Cross-sectional
      observational study of HCWs conducted at Saudi Aramco Medical Services
      Organization (SAMSO) in February 2009. PATIENTS AND METHODS: A self-administered
      questionnaire was distributed to 250 individuals and 161 (64.4%) were completed.
      RESULTS: Of the total respondents, 66 (41%) were Arab, 55 (34.2%) were Asian/Far
      East, and 40 (24.8%) were of other nationalities. A total of 65 (40.4%) responses
      were from physicians and nurses, and 96 (59.6%) were from other HCWs. Of all the
      responders, 152 (94.4%) were aware of the H1N1 influenza situation, and 135
      (83.9%) stated they had received enough information about the current situation.
      Of all the respondents, 59 (36.6%) stated that they received the seasonal
      influenza vaccination in 2008-2009, and 50 (31.1%) expressed their willingness to
      take the 2009 H1N1 vaccine. A total of 24 (14.9%) stated that the vaccine
      contains thiomersal, 21 (13%) stated that the vaccine contains adjuvants, 19
      (11.8%) stated it contains squalene, 17 (10.6%) thought the vaccine causes
      infertility, and 29 (18%) thought the vaccine causes Guillain-Barre syndrome. In
      a multivariate analysis, the following factors were noted to be important in
      choosing to be vaccinated: being Asian, not being a doctor or a nurse, and
      previous acceptance of the seasonal influenza vaccine (P<=.01). CONCLUSIONS: The
      acceptance of the current 2009 pandemic H1N1 vaccine was low. Important factors
      associated with the increasing H1N1 influenza vaccine acceptance include being
      Asian, not being a doctor or a nurse, and previous acceptance of the seasonal
      influenza vaccine.

PMID- 22156643
TI  - Perspectives on specialist nursing in Saudi Arabia: a national model for success.
AB  - In many parts of the world, vulnerable patient populations may be cared for by a
      clinical nurse specialist (CNS). Nurses desiring to develop themselves
      professionally in the clinical arena, within the specialty of their choice, have
      the opportunity to obtain the knowledge, skills, experience and qualifications
      necessary to attain advanced practice positions such as CNS or nurse consultant
      (NC). Although studies have demonstrated the benefits of such roles and while the
      World Health Organization (WHO) recommends it, advanced nursing practice is not
      yet integrated into the health care culture in Saudi Arabia. The reasons for this
      are multiple, but the most important is the poor image of clinical nursing
      throughout the country. This article aims to share a perspective on CNS practice,
      while casting light on some of the obstacles encountered within Saudi Arabia. A
      model is proposed representing specialist nurse-physician collaborative practice
      for implementation nationally. The model has been implemented in the care of the
      colorectal and stoma patient populations while taking into consideration patient
      population needs and local health care culture. This model is based on the
      concepts of holistic "patient-centered care", specialist nurse-physician
      collaborative practice, and the four practice domains for NCs (expert practice,
      leadership, research and education) as indicated by the Department of Health in
      the United Kingdom. We suggest this model will enable the introduction of
      advanced specialist nursing and collaborative partnerships in Saudi Arabia with
      benefits for patients, physicians, health care organizations and the nursing
      profession as a whole.

PMID- 22156642
TI  - Human stromal (mesenchymal) stem cells: basic biology and current clinical use
      for tissue regeneration.
AB  - Human stromal (mesenchymal) stem cells (hMSC) represent a group of non
      hematopoietic stem cells present in the bone marrow stroma and the stroma of
      other organs including subcutaneous adipose tissue, placenta, and muscles. They
      exhibit the characteristics of somatic stem cells of self-renewal and multi
      lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts,
      adipocytes, chondrocytes and possibly other cell types including hepatocytes and
      astrocytes. Due to their ease of culture and multipotentiality, hMSC are
      increasingly employed as a source for cells suitable for a number of clinical
      applications, e.g., non-healing bone fractures and defects and also non-skeletal
      degenerative diseases like heart failure. Currently, the numbers of clinical
      trials that employ MSC are increasing. However, several biological and
      biotechnological challenges need to be overcome to benefit from the full
      potential of hMSC. In this current review, we present some of the most important
      and recent advances in understanding of the biology of hMSC and their current and
      potential use in therapy.

PMID- 22156644
TI  - Novel influenza A (H1N1) virus-induced hemophagocytosis: first case reported in
      Saudi Arabia.
AB  - H1N1 is a novel subtype of the influenza A virus. Since its reemergence in 2008,
      it has been reported to cause a variety of illnesses ranging from mild flu-like
      symptoms to severe multiorgan failure. We report a case of a young
      immunocompetent man who presented with progressive shortness of breath and
      rapidly developed multiorgan dysfunction, including pancytopenia from H1N1
      infection during the 2010-2011 influenza season. His H1N1 pneumonia caused severe
      acute respiratory distress syndrome, respiratory failure requiring mechanical
      ventilation, rhabdomyolysis, myocarditis, hepatitis, encephalitis, and renal
      failure. During the diagnostic workup, a bone marrow biopsy was performed,
      showing hemophagocytosis secondary to the H1N1 infection. Unfortunately the
      patient died despite aggressive measures. Published reports contain only a few
      records of H1N1-induced hemophagocytosis. This is the first case report from
      Saudi Arabia with H1N1-induced secondary hemophagocytosis. It also highlights the
      fact that the virus is still very virulent and will pose a major annual health
      risk along with the seasonal influenza for at least the next few years.

PMID- 22156645
TI  - Multiple magnet ingestion: is there a role for early surgical intervention?
AB  - Children often swallow foreign bodies. Multiple magnet ingestion is rare, but can
      result in serious complications. This study presents three unique cases of
      multiple magnet ingestion: one case an 8-year-old boy with multiple magnet
      ingestion resulting in gastric obstruction and the other two cases with
      intestinal perforations due to multiple magnet intake. History and physical
      examination are unreliable in children who swallow multiple magnets. Sometimes
      radiological findings are not conclusive, whether one magnet is swallowed or
      more. If magnets are not moved in sequential radiology images, we recommend early
      surgical intervention before gastrointestinal complications develop. Toy
      companies, parents, physicians, and radiologists should be warned about the
      potential complications of such toys.

PMID- 22156646
TI  - A lower-cost protocol for sickle cell disease neonatal screening in Tunisia.
AB  - BACKGROUND AND OBJECTIVES: Sickle cell disease (SCD) is a group of hereditary
      chronic anemias that manifest essentially as painful crisis and susceptibility to
      infection. Neonatal screening is a preventive action that reduces the rates of
      mortality due to complications arising from infections by encouraging early
      prophylactic penicillin use and pneumococcal vaccination. The purpose of this
      pilot study was to set up a neonatal screening protocol at a lower cost than one
      that uses commercially available screening kits. DESIGN AND SETTING: Pilot study
      conducted over 1 year in two Tunis maternity hospitals. PATIENTS AND METHODS:
      Samples from 9148 newborns were collected using paper printed using a common
      office printer to collect blood spots from the newborns. A lab-prepared agarose
      gel for isoelectrofocusing (IEF) was used to test the dried blood samples from
      these newborns. RESULTS: The IEF on lab-prepared agarose gels was efficient since
      it was able to detect the main abnormal Hbs previously identified in the Tunisian
      population (HbS, HbC, HbO, and HbG). Furthermore, when data collected in this
      screening program were compared with the previously established national data, no
      statistically significant differences were found. After analysis, results were
      given back to the families of the patients, and the major Hb cases were directed
      to one of the hemoglobinopathies specialized centers, where at-risk couples
      benefited from genetic counselling and were informed about the possibility of
      prenatal diagnosis. CONCLUSION: This pilot experiment demonstrated the
      feasibility of SCD neonatal detection using a lower cost method as well as
      detection of other main structural Hb variants.

PMID- 22156647
TI  - 2009 H1N1 influenza A in children: a descriptive clinical study.
AB  - BACKGROUND AND OBJECTIVE: The 2009 H1N1 was a new influenza virus causing illness
      in people. Especially those younger than 5 years of age and those who have high
      risk medical conditions are at increased risk for influenza-related
      complications. In the present study, we describe the clinical presentation of the
      H1N1 cases attending Jeddah Clinic Hospital-Al Kandarah (JCH-K) in the time
      period from October 2009 to January 2010, and identified the high-risk age
      groups. DESIGN AND SETTING: Prospective study at JCH-K from October 2009 through
      January 2010. PATIENTS AND METHODS: All pediatric patients (up to 15 years old)
      presenting with influenza-like illnesses in the clinics during the specified
      period were clinically examined and tested using reverse transcriptase polymerase
      chain reaction. Only confirmed H1N1 cases were included in the study. RESULTS:
      Over a 4-month period, 89 cases of laboratory-confirmed H1N1 were reported in JCH
      K. Thirty-four patients (38.2%) were younger than 5 years of age. Forty-six
      (51.6%) cases were males. Thirty-three cases were Saudis (37.1%). The most
      commonly reported symptom was fever, which was noted in all cases. Twenty-eight
      cases (31.5%) had pneumonia. Fourteen cases (15.7%) were known asthmatics. Fifty
      two (58.4%) cases were lymphopenic and 32 (35.9%) cases were leucopenic. Sixty
      five (73%) patients were hospitalized, and five of them were treated in the
      intensive care unit. CONCLUSIONS: Even though the majority of cases of the 2009
      pandemic influenza A H1N1 were mild, a severe disease does occur in children. In
      view of delayed PCR results, clinical presentation and lymphopenia were used as
      diagnostic criteria to start antiviral treatment as early as possible. No deaths
      were attributed to the 2009 pandemic.

PMID- 22156648
TI  - Unilateral primary pulmonary agenesis and hypoplasia in monozygotic twins.
AB  - We describe 10-month-old identical female twin infants, one with primary left
      sided pulmonary agenesis and the other with primary left-sided pulmonary
      hypoplasia. They came to our outpatient clinic complaining of persistent dry
      cough. The clinical examination revealed decreased air entry over the left
      hemithorax. Chest x-rays showed complete left-sided radio-opacity in both the
      twins. The chest computed tomography scan with contrast confirmed the diagnoses
      of left-sided pulmonary agenesis (twin A) and left-sided hypoplasia (twin B). No
      other associated congenital anomaly was noted in either of the twins. To our
      knowledge, such a condition in live monozygotic twins has not been previously
      reported in published studies.

PMID- 22156649
TI  - Death of a clinical sign.

PMID- 22156650
TI  - RE: Pattern of presentation in type 1 diabetic patients at the diabetes center of
      a university hospital.

PMID- 22156652
TI  - Epiploic appendagitis: an uncommon nonsurgical cause of acute abdomen.

PMID- 22156654
TI  - Vitamin D-mentia: randomized clinical trials should be the next step.
AB  - Hypovitaminosis D is highly prevalent in the elderly. Its possible role in the
      pathogenesis of Alzheimer's disease (AD) is particularly important, as AD remains
      a public health concern with no current efficient treatment. Vitamin D
      administration could be a multitarget stabilizing treatment for AD since vitamin
      D simultaneously targets several factors leading to neurodegeneration through
      immunoregulatory, antioxidant and anti-ischemic actions, as well as the
      regulation of neurotrophic factors, acetylcholine neurotransmitter and clearance
      of amyloid beta peptide, and the avoidance of hyperparathyroidism. By preventing
      neuronal loss, the question is whether correcting hypovitaminosis D among older
      adults could also prevent AD-related cognitive decline. The cross-sectional
      associations between the vitamin D intakes--whether from diet, sun exposure or
      drug supplements--and cognition strengthened this hypothesis, but prevented the
      finding of a cause and effect link. Pre-post studies showed an improvement of
      cognition concomitant with the increase in 25-hydroxyvitamin D concentrations.
      One randomized trial found that supraphysiological doses of vitamin D were not
      better than physiological doses at improving cognition in AD. At this stage, only
      clinical trials testing vitamin D supplements versus placebo can further
      determine the impact of vitamin D administration on cognition and AD with higher
      levels of evidence.

PMID- 22156655
TI  - Extracellular signal-regulated kinase 1 and 2 are not required for GnRH neuron
      development and normal female reproductive axis function in mice.
AB  - BACKGROUND/AIMS: Selective deletion of extracellular signal-regulated kinase
      (ERK) 1 and ERK2 in the pituitary gonadotrope and ovarian granulosa cells
      disrupts female reproductive axis function. Thus, we asked if ERK1 and ERK2 are
      critical for GnRH neuron ontogeny or the central control of female reproductive
      function. METHODS: GnRH-Cre-recombinase (Cre+) expressing mice were crossed with
      mice with a global deletion of ERK1 and a floxed ERK2 allele (Erk1-/Erk2fl/fl) to
      selectively delete ERK2 in GnRH neurons. RESULTS: Cre-recombinase mRNA was
      selectively expressed in the brain of Cre+ mice. GnRH neuron number and location
      were determined during embryogenesis and in the adult. GnRH neuron counts at E15
      did not differ between experimental and control groups (1,198 +/- 65 and 1,160 +/
      80 respectively, p = NS). In adults, numbers of GnRH neurons in the GnRHCre+Erk1
      /Erk2- mice (741 +/- 157) were similar to those in controls (756 +/- 7), without
      alteration in their distribution across the forebrain. ERK1 and 2 deficiency did
      not alter the timing of vaginal opening, age at first estrus, or estrous
      cyclicity. CONCLUSIONS: Although ERK1 and 2 are components of a dominant
      signaling pathway in GnRH neuronal cells that modulates survival and control of
      GnRH gene expression, other signaling pathways compensate for their deletion in
      vivo to allow GnRH neuron survival and targeting and normal onset of female
      sexual maturation and reproductive function. In contrast to effects at the
      pituitary and the ovary, ERK1 and ERK2 are dispensable at the level of the GnRH
      neuron.

PMID- 22156656
TI  - Pilot study of a pediatric metronomic 4-drug regimen.
AB  - BACKGROUND: Metronomic chemotherapy (MC) is defined as the frequent
      administration of chemotherapy at doses below the maximal tolerated dose and with
      no prolonged drug-free break. MC is gaining interest as an alternative strategy
      to fight resistant cancer. OBJECTIVE: to assess the safety of 4 drug MC regimen
      in paediatric patients with refractory or relapsing various tumour types.
      SETTING: From November 2008 to December 2010, in three academic paediatric
      oncology centers, 16 children (median age 12 years old; range 5.5-20) were
      included in this pilot study. This treatment was proposed to children with
      refractory disease for whom no further effective treatments were available. Most
      frequent diagnosis were medulloblastoma/cerebral PNET (5) osteosarcoma (5), and
      one case each of nephroblastoma, high grade glioma, Hodgkin lymphoma,
      rhabdomyosarcoma, neuroblastoma and kidney rhabdoid tumour. The MC regimen
      consisted in cycles of 56 days (8 weeks) with weekly vinblastine 3 mg/m2 (week 1
      7), daily cyclophosphamide 30 mg/m2 (days 1-21), and twice weekly methotrexate 10
      mg/m2 (days 21-42), and daily celecoxib 100 mg to 400 mg twice daily (days 1-56)
      followed by a 2-weeks chemotherapy break. Adverse events were determined through
      laboratory analysis and investigator observations. RESULTS: One objective
      response was observed in a patient with Hodgkin lymphoma, and 4 patients
      experienced disease stabilization and continued their treatment for 3 cycles (24
      weeks) or more. At last follow-up, 7 patients (43%) are alive including 1 still
      undergoing treatment. During the overall 36 cycles of treatments received by
      patients, 4 grade IV toxicities and 24 grade III toxicities were observed in 11
      cycles in only 10 different patients. CONCLUSION: The metronomic regimen we
      report here was well tolerated and associated with disease stabilization. This
      regimen is currently being evaluated in a national multicenter phase II study.

PMID- 22156657
TI  - Growth kinetics in von Hippel-Lindau-associated renal cell carcinoma.
AB  - OBJECTIVE: To evaluate the growth kinetics of renal cell carcinoma (RCC) in von
      Hippel-Lindau (VHL) disease in a large trial by CT/MRI scan. VHL disease is a
      multisystemic disorder predisposing to renal cysts and cancer. There is a general
      assumption that VHL-associated RCC presents slower growth rates than sporadic
      RCC. PATIENTS AND METHODS: We describe growth kinetics of 96 renal tumours in 64
      VHL patients with analysed germline mutation (54/64 treated, 10/64 active
      surveillance) over a mean follow-up of 54.9 months. We calculated tumour volume,
      growth rate, multiplication of tumour volume per year and overall, as well as
      tumour volume doubling time. RESULTS: The mean growth rate of 96 tumours was 4.4
      mm/year (SD 3.2, median 4.1 mm/year), mean volume doubling time was 25.7 months
      (SD 20.2, median 22.2 months). We saw a median 1.4-fold increase in tumour volume
      per year. At treatment time point, VHL kidneys comprised 39% tumour and 15.7%
      cyst volume fraction. We saw no correlation between tumour size and growth
      parameters. CONCLUSION: VHL-associated RCC show large variances in tumour growth
      behaviour. Compared to the literature, in our study the growth rates (mm/year) of
      RCC in VHL disease did not differ from those of sporadic RCC. Fast tumour growth
      increases the risk for metastases.

PMID- 22156658
TI  - Vaccination therapy for non-small-cell lung cancer: review of agents in phase III
      development.
AB  - The historical results of cancer vaccination for non-small-cell lung cancer
      (NSCLC) were disappointing. In the current decade, however, new insights in the
      interaction between tumours and the immune system have led to the development of
      immunotherapy as a fundamentally new concept for the treatment of NSCLC. Modern
      NSCLC vaccine strategies rely on better identification of antigenic targets,
      addition of strong immunoadjuvants, and use of more efficient delivery systems.
      These treatments have convincingly demonstrated to elicit potent immune responses
      and have shown promising efficacy signals and excellent tolerability in phase II
      randomised studies. This-together with recent positive phase III data in
      indications other than NSCLC-has helped to establish the proof of principle for
      cancer vaccination. In NSCLC, ongoing phase III trials are investigating this
      approach in different treatment settings: the Melanoma AntiGEn A3 vaccine in
      resected early-stage NSCLC, the L-BLP25 vaccine in locally advanced NSCLC after
      chemoradiotherapy, and belagenpumatucel-L, the epidermal growth factor and the
      TG4010 vaccine in advanced stage, either as an adjunct to chemotherapy or as
      maintenance after completion of chemotherapy. Mode of action, development,
      available clinical data, and currently ongoing phase III studies are reviewed.

PMID- 22156659
TI  - Adaptation of genotype 3 hepatitis E virus in Eastern China and inverse
      correlation with genotype 4 hepatitis E virus.
AB  - We studied the distribution and development of hepatitis E virus (HEV) genotypes
      3 and 4 in pig farms located within the Shanghai metropolitan area. A total of
      1,487 swine fecal samples were collected from 39 pig farms during 2009-2010. The
      average incidence rates for genotype 3 and genotype 4 HEV were 10.6 and 9.3%,
      respectively. The frequencies of genotype 3 and genotype 4 HEV among the farms
      were inversely related (r = -0.7423), suggesting that the two genotypes competed
      within the environmental niche provided by the porcine host. In addition, all of
      the farms tested positive for both genotype 3 and genotype 4 HEV, indicating that
      the former is becoming more prevalent in the Shanghai area. The overall HEV
      incidence rate during 2009-2010 was 20%, which supports the existence of
      homeostasis within the porcine HEV reservoir.

PMID- 22156660
TI  - QT prolongation and torsade de pointes induced by fluoroquinolones: infrequent
      side effects from commonly used medications.
AB  - Although very useful agents, fluoroquinolones are associated with a number of
      adverse events, some with considerable clinical significance. Prolongation of the
      QT interval, for example, is an adverse effect associated with the use of
      fluoroquinolones. Fluoroquinolones prolong the QT interval by blocking voltage
      gated potassium channels, especially the rapid component of the delayed rectifier
      potassium current I(Kr), expressed by HERG (the human ether-a-go-go-related
      gene). According to the available case reports and clinical studies, moxifloxacin
      carries the greatest risk of QT prolongation from all available quinolones in
      clinical practice and it should be used with caution in patients with
      predisposing factors for Torsades de pointes (TdP). Although gemifloxacin,
      levofloxacin, and ofloxacin are associated with a lower risk of QT prolongation
      compared with moxifloxacin, they should also be used with caution in patients at
      risk for QT prolongation. Ciprofloxacin appears to be associated with the lowest
      risk for QT prolongation and the lowest TdP rate. The overall risk of TdP is
      small with the use of fluoroquinolones. Clinicians can minimize that risk by
      avoiding prescriptions of multiple medications associated with QT-interval
      prolongation, especially in high-risk patients.

PMID- 22156661
TI  - Is intensive cholesterol lowering detrimental in multiple sclerosis?

PMID- 22156663
TI  - Comparison of retention rates of fissure sealants using two flowable restorative
      materials and a conventional resin sealant: two-year follow-up.
AB  - OBJECTIVE: The purpose of this clinical study was to compare the retention rates
      of two flowable restorative systems (Admira Flow and Grandio Flow) with that of a
      conventional resin-based sealant (Fissurit F). MATERIALS AND METHODS: The study
      was planned as a clinical trial with a split-mouth design. A total of 122
      sealants (38 Admira Flow, 41 Grandio Flow, 43 Fissurit F) were randomly applied
      to completely erupted permanent molars in 35 patients aged 9-20 years and
      followed up for 24 months. Data were analyzed using Pearson's chi(2) and multiple
      comparison tests. RESULTS: At the end of the follow-up period, Fissurit F had
      higher retention rates (81.0%) than both Admira Flow (60.5%) and Grandio Flow
      (57.1%), with p < 0.05. However, there was no significant difference in caries
      development among groups (p > 0.05). CONCLUSION: The two flowable composite resin
      materials used as fissure sealant were less retentive than the conventional resin
      sealant.

PMID- 22156662
TI  - Measurement equivalence in ADL and IADL difficulty across international surveys
      of aging: findings from the HRS, SHARE, and ELSA.
AB  - OBJECTIVE: To examine the measurement equivalence of items on disability across
      three international surveys of aging. METHOD: Data for persons aged 65 and older
      were drawn from the Health and Retirement Survey (HRS, n = 10,905), English
      Longitudinal Study of Aging (ELSA, n = 5,437), and Survey of Health, Ageing and
      Retirement in Europe (SHARE, n = 13,408). Differential item functioning (DIF) was
      assessed using item response theory (IRT) methods for activities of daily living
      (ADL) and instrumental activities of daily living (IADL) items. RESULTS: HRS and
      SHARE exhibited measurement equivalence, but 6 of 11 items in ELSA demonstrated
      meaningful DIF. At the scale level, this item-level DIF affected scores
      reflecting greater disability. IRT methods also spread out score distributions
      and shifted scores higher (toward greater disability). Results for mean
      disability differences by demographic characteristics, using original and DIF
      adjusted scores, were the same overall but differed for some subgroup comparisons
      involving ELSA. DISCUSSION: Testing and adjusting for DIF is one means of
      minimizing measurement error in cross-national survey comparisons. IRT methods
      were used to evaluate potential measurement bias in disability comparisons across
      three international surveys of aging. The analysis also suggested DIF was
      mitigated for scales including both ADL and IADL and that summary indexes (counts
      of limitations) likely underestimate mean disability in these international
      populations.

PMID- 22156664
TI  - A randomised trial comparing the antibacterial effects of dentine primers against
      bacteria in natural root caries.
AB  - As people are living longer and retaining their teeth into old age, root caries
      is an increasingly significant problem. A minimally invasive treatment strategy,
      involving sealing the root caries lesion with an antibacterial resin sealant,
      could be highly beneficial. The aim of this study was to compare the
      antibacterial properties of the primers of two proprietary dentine bonding
      agents, Clearfil SE Bond (SE; Kuraray Medical, Japan) and Clearfil Protect Bond
      (PB; Kuraray Medical), which contains the antibacterial monomer
      methacryloyloxydodecylpyridinium bromide. Fifty-two root caries lesions were
      identified and randomly assigned to a primer. The lesion was cleaned, isolated,
      sampled with a sharp spoon excavator, a primer applied and a second sample taken.
      Samples were transported in fastidious anaerobe broth, vortex-dispersed and
      serial dilutions inoculated onto selective agars. Reduction in colony-forming
      units (CFU, %) after primer application was calculated for both primers for
      bacterial growth on each selective agar and compared to a hypothesised mean of
      100% (one-sample t test, p < 0.05). No significant differences between primers
      were seen, indicating efficient bacterial elimination by both materials.
      Comparing percent reduction between SE and PB for each agar (Mann-Whitney test, p
      < 0.05), a significantly greater CFU reduction by PB was seen for streptococci
      but not other bacteria. More lesions exhibited bacterial growth and several
      lesions demonstrated marked bacterial growth after treatment with SE compared
      with PB. Therefore, PB appears to exhibit superior antimicrobial properties,
      particularly against streptococci. Both primers are highly antibacterial towards
      root caries bacteria and may therefore be suitable for minimally invasive
      treatment.

PMID- 22156665
TI  - Synchronous colorectal cancers: a review of clinical features, diagnosis,
      treatment, and prognosis.
AB  - BACKGROUND/AIMS: With the development of early diagnostic technologies, more
      synchronous colorectal cancers (SCRCs) can be clinically detected. Although SCRCs
      are recognized as a significant clinical entity, their clinical features,
      diagnosis, treatment, and prognosis have yet to be definitively established. In
      order to obtain a comprehensive understanding of this disease and to establish an
      efficient profile by which to recognize individuals at high risk of developing
      SCRCs, we carried out a review of the relevant literature. METHODS: The PubMed
      database was searched for publications of 'synchronous colorectal
      carcinoma/cancer/adenocarcinoma' and 'multiple colorectal carcinomas'. All
      publications up to January 2011 were considered, and then only articles in
      English were retrieved for inclusion in this review. RESULTS: The incidence of
      SCRCs was found to be higher in older and male patients. The prognosis in
      patients with SCRCs was equivalent to that in patients with solitary CRC. The
      failure to diagnose synchronous lesions before and during the operation was
      associated with repeated surgery. CONCLUSION: SCRCs possess distinctive features
      compared to solitary CRC. While all colorectal patients should be carefully
      assessed to rule out the presence of concurrent colon adenomas, since missed
      lesions can result in additional surgery and poor prognosis, particular attention
      should be given to the high-risk group of older male patients.

PMID- 22156666
TI  - Junction site analysis of chimeric CYP21A1P/CYP21A2 genes in 21-hydroxylase
      deficiency.
AB  - BACKGROUND: Chimeric CYP21A1P/CYP21A2 genes, caused by homologous recombination
      between CYP21A2 (cytochrome P450, family 21, subfamily A, polypeptide 2) and its
      highly homologous pseudogene CYP21A1P (cytochrome P450, family 21, subfamily A,
      polypeptide 1 pseudogene), are common in patients with congenital adrenal
      hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). A comprehensive
      junction site analysis of chimeric CYP21A1P/CYP21A2 genes is needed for
      optimizing genetic analysis strategy and determining clinical relevance. METHODS:
      We conducted a comprehensive genetic analysis of chimeric CYP21A1P/CYP21A2 genes
      in a cohort of 202 unrelated 21-OHD patients. Targeted CYP21A2 mutation analysis
      was performed, and genotyping of chimeric CYP21A1P/CYP21A2 genes was cross
      confirmed with Southern blot, RFLP, and multiplex ligation-dependent probe
      amplification analyses. Junction sites of chimera genes were determined by
      sequencing the long-PCR products amplified with primers CYP779f and Tena32F. An
      updated bioinformatics survey of Chi-like sequences was also performed. RESULTS:
      Of 100 probands with a chimeric allele, 96 had a chimera associated with the
      severe classic salt-wasting form of CAH, and the remaining 4 carried an uncommon
      attenuated chimera with junction sites upstream of In2G (c.293-13A/C>G), which is
      associated with a milder phenotype. In addition to 6 of 7 reported chimeras, we
      identified a novel classic chimera (CH-8) and a novel attenuated chimera (CH-9).
      Attenuated chimeras explained prior genotype-phenotype discrepancies in 3 of the
      patients. Sequencing the CYP779f/Tena32F amplicons accurately differentiated
      between classic and attenuated chimeras. The bioinformatics survey revealed
      enrichment of Chi-like sequences within or in the vicinity of intron 2.
      CONCLUSIONS: Junction site analysis can explain some genotype-phenotype
      discrepancies. Sequencing the well-established CYP779f/Tena32F amplicons is an
      unequivocal strategy for detecting attenuated chimeric CYP21A1P/CYP21A2 genes,
      which are clinically relevant.

PMID- 22156667
TI  - Exhaled endogenous particles contain lung proteins.
AB  - BACKGROUND: We recently developed a novel, noninvasive method for sampling
      nonvolatile material from the distal airways. The method is based on the
      collection of endogenous particles in exhaled air (PEx). The aim of this study
      was to characterize the protein composition of PEx and to verify that the origin
      of PEx is respiratory tract lining fluid (RTLF). METHOD: Healthy individuals
      exhaled into the sampling device, which collected PEx onto a silicon plate inside
      a 3-stage impactor. After their extraction from the plates, PEx proteins were
      separated by SDS-PAGE and then analyzed by LC-MS. Proteins were identified by
      searching the International Protein Index human database with the Mascot search
      engine. RESULTS: Analysis of the pooled samples identified 124 proteins. A
      comparison of the identified PEx proteins with published bronchoalveolar lavage
      (BAL) proteomic data showed a high degree of overlap, with 103 (83%) of the PEx
      proteins having previously been detected in BAL. The relative abundances of the
      proteins were estimated according to the Mascot exponentially modified protein
      abundance index protocol and were in agreement with the expected protein
      composition of RTLF. No amylase was detected, indicating the absence of saliva
      protein contamination with our sampling technique. CONCLUSIONS: Our data strongly
      support that PEx originate from RTLF and reflect the composition of undiluted
      RTLF.

PMID- 22156668
TI  - Circulating troponin as measured by a sensitive assay for cardiovascular risk
      assessment in primary prevention.
AB  - BACKGROUND: Measuring circulating cardiac troponin using novel sensitive assays
      has revealed that even minute elevations are associated with increased mortality
      in patients with coronary artery disease or even in the general population. Less
      well defined, however, is the incremental value of measuring circulating cardiac
      troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention.
      METHODS: We measured circulating concentrations of cTnI, N-terminal pro-B-type
      natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP)
      in 5388 individuals free of known cardiovascular disease recruited into the
      DETECT study, a prospective longitudinal population-based cohort study. We
      determined the prognostic implications for incident major adverse cardiovascular
      events (MACE) during 5 years of follow-up. RESULTS: Circulating cTnI was
      detectable in 19% of the subjects. Increased cTnI concentrations were associated
      with established risk factors for atherosclerosis and demonstrated a graded
      relationship with all-cause mortality and incident MACE during 5-year follow-up.
      A single measurement of cTnI significantly improved risk prediction over
      established risk factors, and also added prognostic information, when adjusted
      for serum concentrations of NT-proBNP and hsCRP. CONCLUSIONS: Minute increases in
      cTnI are associated with increased mortality and incident MACE in a large primary
      prevention cohort and, thus, identify contributors to cardiovascular risk not
      fully captured by traditional risk factor assessment.

PMID- 22156669
TI  - [Etiopatogenezis clinic end treatment of diabetic rethinopathy].
AB  - This article contains analyses of etiopathogenezis clinic treatment data provided
      by different literature on diabetic rethinopathy. Diabetic rethinopathy is the
      main reason for blindness and lost vision. The article highlights modern views on
      ethiopathogenezis clinic and treatment of diabetic retinopathy. The paper
      considers the methods of laser coagulation, intravitreal injection of avastin in
      vitreus body and for deep stages of diabetic rethinopathy - application of
      surgery as advanced means for treatment.

PMID- 22156670
TI  - [Reaction of gingival mucosa on the biodegradated film under chronic
      periodontitis treatment: morpho-functional correlation].
AB  - Purpose - to study the morphological justification of biopolymer film on the
      gingival mucosa in chronic periodontitis.  The samples of gingival mucosa from 42
      patients with moderate degree of chronic periodontitis in the acute stage were
      researched. We determined the specific stomatologic indices of oral cavity and
      periodontal pocket depth. Treatment started with application to the gingiva
      biopolymer film with different ingredients (antibiotics etc.). Morphology and
      ultrastructure of epithelial component was investigated after 24 hours, 7 days
      and 3 months. Clinical indicators were estimated in the dynamics (24, 48 hours, 7
      10 days, 3 months). Based on histo-ultrastructural data of strutified squamous
      epithelium and stomatologic indices of the oral cavity, we can conclude that the
      use of biodegradable polymer film leads to the regression of the process,
      reducing periodontal pocket depth, repair germinal and upper layers of
      epithelium, and in general, activates the reparative and regenerative processes
      in the gingival mucosa.

PMID- 22156671
TI  - Results of accelerated hyperfractionated radiotherapy for esophageal cancer
      performed by field-in-field technique.
AB  - During the treatment the objective therapeutical effect was found in 227 (58.8%)
      patients, of which the complete effect was reached in 23,6%, partial - in 35.2%
      of cases. In 20 (21.9%) of the 91 patients who completed treatment with complete
      remission, during the period of observation, recurrences in the irradiated zones
      were observed.  It was found that according to all the studied indexes, result of
      the treatment of patients that received radiation therapy in the mode of
      accelerated hyperfractionation proved to be statistically better than after the
      classic course of radiotherapy.

PMID- 22156672
TI  - [Concept of optimal body composition of professional football players].
AB  - Body composition and body weight are two of the many factors that contribute to
      optimal exercise performance. Body weight can influence an athlete's speed,
      endurance, and power, whereas body composition can affect an athlete's strength,
      agility, and appearance. Individualized assessment of an athlete's body
      composition and body weight or body image may be advantageous for the improvement
      of athletic performance. The purpose of the present research consists in
      development of physiologically proved modelling characteristic of high
      performance football players on the basis of the analysis of dynamics (changes)
      of the major parameters of structure of weight of football players of various
      ages in process of acquiring game experience and skill. 344 football players from
      15 to 35 years old were surveyed. The basic parameters of body composition were
      determined. It was found that general tendency in dynamics of the basic
      components of structure of body composition at the end of playing season is
      expressed in appreciable gain of active cellular weight as analogue of the
      muscular mass, decrease in the absolute fat contents, increase in endocellular
      liquid and eritrocyte mass. Comparison of changeable parameters to external
      criteria of success in competition and tested productivity, adaptive reactions
      and stability of motivation led to the conclusion that quantitative sports-skill
      evaluation and forecast of the growth in achievements is possible.

PMID- 22156673
TI  - [Influence of an exercise therapy on primary chronic constipation].
AB  - During the primary chronic constipation increase of exercise stress is a commonly
      recognized recommendation, but not existence of specific schemes and forms of
      tension, restricts wide usage of this method. Subject of the research was the
      evaluation of exercise therapy effectiveness in patients with primary chronic
      constipation. The research was carried out on 15 patients, who were undergone
      exercise therapy sessions for their stoutness and spinal pathologies. Research
      group consisted of 8 patients with irritable intestine syndrome, who were
      provided by standard treatment. All researched patients kept a diary, with
      numeral evaluation of defecation type. Analysis of the findings displayed
      satisfactory effectiveness of the exercise therapy during the primary chronic
      constipation.

PMID- 22156674
TI  - [Expression of the growth factors in the goitertransformed thyroid gland:
      correlation with the clinical-morphological and electron-microscopic
      characteristics].
AB  - The purpose of the investigation consisted in the study of morphological versions
      and activity of immunoselective markers in the epithelial component of the
      goitertransformed thyroid gland with the association of electron-microscopic
      changes and clinical manifestation of disease. As the primary antibodies were
      used mono- and polyclonal antibodies to the thyroid stimulating hormone (TSH),
      the vascular endothelial growth factor (VEGF) and the epidermal growth factor
      receptor (EGFR). It is established that the high expression of VEGF is observed
      in thyroid tissue, which loses sensitivity to the thyroid stimulating hormone,
      and vice versa. Hyperexpression of TSH, VEGF and EGFR in the nodular
      proliferating and adenomatous goiter indicates intensification of hyperplastic
      processes, the unbalance between clinical manifestation of disease and its
      biological potential of growth, which plays the key role in the determination of
      clinical prognosis of malignant potential of the nodular formation and
      postoperative relapse.

PMID- 22156675
TI  - Beta-cells of rats pancreas and their supposed precursors during alloxan diabetes
      and after the action of Plaferon LB.
AB  - Using the methods of light and electron microscopy, pancreas was studied in the
      experimental model (Rats-30) of alloxan diabetes - one month from alloxan
      injection and after the action of Plaferon LB (amniotic interferon). Special
      emphasis was made on display of extra-islet cells. Data obtained suggest that
      extra-islet cells exist in the rats pancreas with alloxan diabetes. Some of these
      cells were located near the acini, others were in close contact with duct cells.
      The border between acinar and extra islet cells were well preserved. Plaferon LB
      has shown positive influence on the content of sugar in the blood of the rats
      with alloxan diabetes. After the action of Plaferon LB there were detected extra
      islet cells which contained insulin granules. Investigation have shown that most
      of these cells which can potentially differentiated into beta-cells are extra
      islet cells with granules specific for insulin secreting beta-cells. Some of
      these extra-islet cells including exocrine and endocrine granules. Some of them
      can belong to the pancreas acinar or ductul cells. It is possible, that these
      extra-islet cells have ability differentiate into beta-cells and are their
      precursors. Currently, during pathological processes extra-islet cells are in the
      resting condition and have transitory structure under differentiation into
      insulin producing beta-cells. Presumably Plaferon LB promote maturation and
      differentiation of extra-islet cells and takes part in the renewal processes of
      beta-insulocytes. Investigation have shown, that damaged pancreas has capacity of
      generating new beta-cells after activation with external stimuli.

PMID- 22156676
TI  - Study of physiological and biochemical mechanisms of insulin action on the
      emotional state of anxiety.
AB  - Insulin is an anabolic hormone with a broad spectrum of action.  When linked with
      the specific receptors of the cell membrane insulin causes the changes in the
      whole plasmatic net of the cell and favourable conditions are created for complex
      biochemical processes.  The goal of the research is to study the metabolic effect
      of insulin on the emotional state of the anxiety according to the animal model
      (rats). In order to reach the aim passive avoidance test ("punished water
      drinking") was used in an intact animal model as well as in the one with the
      experimental diabetes mellitus. Pharmacological substances: insulin and dithizone
      were applied.   After insulin injection the intensification of anxiety state in
      central neural system is connected to the activation of the enzyme (thirozin
      amino-transpherasa), which in its turn intensifies formation of amino acids
      (glutamine). The latter through either synaptic or outer-synaptic ways effects
      hippocampus and neurons of the brain tunic causing the increase of excitation and
      consequently intensifies the anxiety state.   It was confirmed that exogenic
      introduction of insulin causes activation of innate behaviours, in particular the
      generation of anxiety emotion, that should be considered by an endocrinologist
      within the whole treatment period of insulin-dependent diabetic patients.

PMID- 22156677
TI  - Alteration in viability and proliferation activity of mitogen stimulated Jurkat
      cells.
AB  - The aim of our study was the establishment of mechanisms of alterations in
      viability and mitogen stimulated T lymphocyte proliferation activity. In PHA
      stimulated Jurkat cells along with increased proliferation level the reduction of
      mitochondrial dehydrogenases activity (by 20%) and rising number of cells with
      low mitochondrial membrane potential (DeltaPsim) was revealed.   It was concluded
      that interaction of mitogen (PHA) with T cells receptors (TCR) contributes
      reduction activity of mitochondrial NADH-dehydrogenase (via phospolipasa C
      diacilglicerol (PLC-DAG)-induced PKCs (PKCalpha, PKCtheta) activation pathway).
      Supression activity of I complex (NADH-dehydrogenase) of mitochondrial
      respiratory chain and reduction of mitochondrial membrane potencial (DeltaPsim)
      is accompanied with intensification of superoxide radicals production. Superoxide
      radicals as secondary messengers involve in the induction of T cells viability
      and proliferative activity regulating genes (CD95L and IL-2) and by this way
      contribute modification of cell proliferation and apoptosis intensity.

PMID- 22156678
TI  - [Professional orientation of medical students--personal training (review)].
AB  - An innate intention of subjects to reach the leading position on a regular job
      scale substantially accentuates the interest to the training study processes. The
      country that owns well-educated physicians possesses a better chance to attain
      the superior position in medical managing innovations. The modern scientific
      knowledge has to invade systematically thus into the ordinary common practice.
      The ambition to qualify the professional resources via regular training courses
      is systematically intensified therefore.  Any person happens to possess several
      alternatives for successes in life. The particular important among is the choice
      of a concrete profession that being motivated by the job dynamics while regulates
      subjects' activities and intensifies personal interests to the training events. 
      The carrier options of young peoples are influenced by various factors. The most
      efficient items from appear the family, friends, surroundings, reading
      literature, television, moviesThe selection of a profession is not finished at
      all by the university entering: due to life circumstances the dramatic shifts in
      definite job objectives can occur later. Correctly organized personal trainings 
      along with conventional group exercises, generally, for medical students and
      young physicians, particularly, can promote the proper choice of fixed carrier
      aims.   Detailed description and showing of appropriate contacts of physicians
      with patients can enrich the capacities of medical students and young physicians
      and can improve their behavior in own practice. University study as well as
      combined group and personal graduate and postgraduate training courses increase
      the activities of involved persons, intensify the trusts for knowledge and love
      to the profession, favor the desire to advance the level of theoretical and
      practical skills, and improve consequently the occupational level.

PMID- 22156679
TI  - Mental disorders of people with disability pension in Georgia.
AB  - Correct assessment due to mental diseases is rather important. WHO developed
      International Classification for Functioning, Disability and Health (ICF) and
      there are two approaches to its implementation - development of disease specific
      or generic core sets. In order to know which way to choose up to date information
      is needed on disorders that most frequently lead to disability in Georgia.   The
      study aimed at identification of the most prevalent mental diseases that led to
      disability pension in Georgia in 2010.  Cross-sectional study of the population
      of pension beneficiaries was conducted. We have calculated 10% of 607 (diagnosed
      with disability in 2010) to be included in the survey. They were selected using
      random sampling method. Patient data were collected from the case histories. 
      Paranoid schizophrenia (F 20.0) was the leading cause of disability both in men
      and women - 51.6% in men and 50% in women. In men persistent delusional disorder
      and mild mental retardation with significant impairment of behavior accounted for
      9.7% each, while in women persistent delusional disorder led to disability in
      15.0% of cases and moderate mental retardation - in 10.0%. All children receiving
      disability pension are mentally retarded.  Paranoid schizophrenia - relatively
      less common disorder has high associated impairment among adults in Georgia,
      whereas in children mental retardation is the most frequent disabling condition.
      However, there are many other diseases that lead to disability. Therefore the
      best way to move further might be to first develop a generic core set for all
      psychiatric disability.

PMID- 22156680
TI  - Safety of patients--actual problem of modern medicine (review).
AB  - Safety of patients is actual problem of up-to-date medicine. The current
      successful treatment of various sicknesses is achieved by implementation in
      clinical practice such medical preparations (medications), which are
      characterized with the high therapeutic activity, low toxicity and prolonged
      effects. In spite of evidence of the pharmacotherapeutical advances, the
      frequency of complications after medication has grown - that is why the safety of
      patients is the acute actual problem of medicine and ecological state of human
      population today.

PMID- 22156681
TI  - [Fatty acid of Chelidonium majus L. oil and its byologikal active as a food
      additive].
AB  - The aim of the study is individual identification of fatty acids in oil of
      Chelidonium majus L. and prediction of its effects as a food-additive. By high
      effective liquid chromatographic methods, fatty acids were fractionated.
      Identification of the fatty acids constituents was based on comparison of their
      retentium time. Their relative concentrations are expressed as percentages of the
      total fatty acid component. The impact of Chelidonium majus L. oil as a food
      additive supplement on the contents of fatty acid in liver lipids of mice was
      determined. Investigations were carried out on 40 imbred mice. The investigation
      showed that the 5% food-additive of Chelidonium majus L. oil fulfil an important
      role in physiological processes in imbred mice livers.

PMID- 22156682
TI  - Changes of locomotor, exploratory and emotional behavior in animal model of
      depression induced by deficiency of brain  monoamine content.
AB  - The character of changes of open field behavior was not studied extensively in
      animal model of depression with deficiency of brain monoamine/serotonin content
      and obtained results are controversial. Both, enhancement and invariability of
      locomotor activity has been obtained. Additional investigation of this question
      is motivated also by insufficient study of exploratory and emotional behaviors in
      animal model of depression of this type.   Animal model of depression was
      developed by chronic administration of Clomipramine and/or Melipramine in rat
      pups from postnatal day 7 (P7) and/or 14 (P14) to P21 and/or P28, respectively.
      Studies of open field behavior were started in adult age rats i.e. 8-12 weeks
      after the end of treatment. Control animals were the same age old.  Two-week
      period of postnatal development starting at the P7 and/or P14 appeared equally
      sensitive to early antidepressant treatment. Modeled animals exhibited
      significant increase of horizontal locomotor activity. Frequency of center
      entrance and the time of staying in the center of open field were increased
      significantly indicating that animal models of depression can not percept really
      the level of stressfulness of novel surroundings. All of these changes indicate
      also to the significant level of exploratory behavior in modeled animals.  
      Postnatal exposure of rat pups to Clomipramine or Melipramine produces
      significant increase of locomotor activity but dos not induces behavioral
      'despair' or "refractory loss of interest" at mature age.

PMID- 22156683
TI  - Effect of antihypertensive therapy on incident stroke in cohorts with
      prehypertensive blood pressure levels: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND AND PURPOSE: Compared with normotensive individuals, there is a higher
      incidence of stroke in patients with hypertensive, as well as prehypertensive,
      blood pressure levels (ie, 120-139/80-89 mm Hg). Although several studies have
      shown that blood pressure reduction in hypertensive patients reduces the
      incidence of cardiovascular events, including stroke, it is still unknown whether
      treatment of prehypertensive blood pressure levels has a similar effect. We
      sought to determine whether reduction in blood pressure in the prehypertensive
      range reduces the incidence of stroke by performing a meta-analysis of randomized
      trials comparing an antihypertensive drug against placebo in cohorts with
      prehypertensive baseline blood pressure levels. METHODS: Randomized controlled
      trials performed with the 95 different antihypertensive agents available in the
      market were identified using MEDLINE, returning a total of 2852 results.
      Exclusion criteria included: average blood pressure of >= 140/90 mm Hg at
      baseline, crossover studies, and lack of a control group receiving placebo.
      RESULTS: A total of 16 trials involving 70 664 patients were included. Patients
      randomized to the active treatment arm had a statistically significant 22%
      reduction in the risk of stroke compared with placebo, with little heterogeneity
      among the trials (I(2), 18.0%; RR, 0.78 [95% CI, 0.71-0.86]; P<0.000001). To
      prevent 1 stroke, 169 patients had to be treated with a blood-pressure-lowering
      medication for an average of 4.3 years. CONCLUSIONS: The risk of stroke is
      significantly reduced with antihypertensive therapy in cohorts with
      prehypertensive blood pressure levels. These findings can have important clinical
      implications.

PMID- 22156684
TI  - Letter by Zhang regarding article, "Diabetes and poor outcomes within 6 months
      after acute ischemic stroke: the China National Stroke Registry".

PMID- 22156685
TI  - Patients with transient ischemic attack with ABCD2 <4 can have similar 90-day
      stroke risk as patients with transient ischemic attack with ABCD2 >=4.
AB  - BACKGROUND AND PURPOSE: It is unclear whether patients with transient ischemic
      attack with an ABCD(2) score <4 can be safely evaluated within the following week
      as recommended by some national guidelines rather than in emergency. METHODS: A
      total of 1679 patients in the SOS-TIA prospective cohort had a definite or
      possible transient ischemic attack and had complete information on ABCD(2) score
      components. They were evaluated and treated as soon as possible in a transient
      ischemic attack clinic with round-the-clock access, 87% of them within 24 hours
      of the first call to medical attention. Criteria for emergency treatment were
      internal carotid or intracranial artery stenosis >=50% or major cardiac source of
      embolism. RESULTS: Primary end point was stroke at 90 days. The 90-day stroke
      rate (number of events/number of patients) was 3.4% (24/701) in patients with
      ABCD(2) score >=4, 3.9% (7/180) in patients with ABCD(2) score <4 and criteria
      for emergency treatment, and 0.4% (3/798) in patients with ABCD(2) score <4 and
      no criteria for emergency treatment (P for between-group comparison <0.0001).
      CONCLUSIONS: When possible, patients with transient ischemic attack should be
      evaluated without delay regardless of ABCD(2) score because some with lower
      scores have treatable causes associated with higher short-term risks of stroke.

PMID- 22156686
TI  - Ablating brain embolism in atrial fibrillation.

PMID- 22156687
TI  - Public awareness of stroke in Korea: a population-based national survey.
AB  - BACKGROUND AND PURPOSE: To date, no large study has been conducted to investigate
      baseline stroke awareness within a nationally representative sample of the Korean
      population. METHODS: A total of 1000 residents were randomly sampled according to
      regional demographic characteristics and were interviewed in person by trained
      interviewers. Structured, open-ended and close-ended questions were asked to
      assess stroke awareness. RESULTS: Among the respondents, 62% reported at least 1
      stroke symptom and 56% reported at least 1 risk factor for stroke in open-ended
      questioning. Multivariate analysis revealed that completion of >=12 years of
      education was independently associated with knowledge of symptoms (OR, 1.527; 95%
      CI, 1.146-2.034) and risk factors (OR, 1.577; 95% CI, 1.175-2.115). Approximately
      31% and 33% of respondents, respectively, had some knowledge of thrombolysis and
      the proper action (call emergency medical services). Compared with subjects aged
      20 to 39 years, those aged 40 to 59 years were more knowledgeable about
      thrombolysis (OR, 1.433; 95% CI, 1.045-1.964) and proper action (OR, 2.291; 95%
      CI, 1.646-3.188). The major source of information about stroke was television
      (59%), and the most reliable source was the respondents' physicians (55%). Among
      respondents 20 to 39 years of age, the Internet (37%) was the second greatest
      source of information. CONCLUSIONS: Stroke awareness was suboptimal in Korea,
      especially among younger citizens and those with less education. To improve their
      knowledge, physicians should exert greater efforts to educate the public about
      stroke using mass media and the Internet.

PMID- 22156688
TI  - Using dabigatran in patients with stroke: a practical guide for clinicians.

PMID- 22156689
TI  - An efficient way to detect poststroke depression by subsequent administration of
      a 9-item and a 2-item Patient Health Questionnaire.
AB  - BACKGROUND AND PURPOSE: The early detection of poststroke depression is essential
      for optimizing recovery after stroke. A prospective study was conducted to
      investigate the diagnostic value of the 9-item and the 2-item Patient Health
      Questionnaire (PHQ-9, PHQ-2). METHODS: One hundred seventy-one consecutive
      patients with stroke who could communicate adequately were included. In the 6th
      to 8th weeks after stroke, depression was measured using the PHQ-9 and PHQ-2 and
      diagnosed using the Composite International Diagnostic Interview. RESULTS: Of the
      participating patients, 20 (12.2%) were depressed. The PHQ-9 performed best at a
      score >=10, a sensitivity of 0.80 (95% CI, 0.62-0.98), and a specificity of 0.78
      (95% CI, 0.72-0.85) and the PHQ-2 at a score >=2 with a sensitivity of 0.75 (95%
      CI, 0.56-0.94) and a specificity of 0.76 (95% CI, 0.69-0.83). Administering the
      PHQ-9 only to patients who scored >=2 on the PHQ-2 improved the identification of
      depression (sensitivity, 0.87; 95% CI, 0.69-1.04). CONCLUSIONS: The diagnostic
      value is acceptable to good for PHQ-9 scores >=10 and PHQ-2 scores >=2.
      Conducting a PHQ-9 only in patients with a PHQ-2 score >=2 generates the best
      results.

PMID- 22156690
TI  - Delay of stroke onset by milk proteins in stroke-prone spontaneously hypertensive
      rats.
AB  - BACKGROUND AND PURPOSE: There is an inverse association between dairy food
      consumption and the incidence of stroke in observational studies. However, it is
      unknown whether the relationship is causal or, if so, what components in milk are
      responsible for reducing the incidence of stroke. METHODS: Stroke-prone
      spontaneously hypertensive rats were fed diets comprising amino acids, proteins
      from different sources (casein, whey, soybean, or egg white), or fats from
      different sources (butter, beef tallow, or cocoa butter) and the onset of stroke
      and lifespan were examined. RESULTS: Increasing the amount of dietary casein (5%
      to 55% of caloric intake) markedly delayed the onset of stroke. However, when
      stroke-prone spontaneously hypertensive rats were fed diets containing 55% of
      caloric intake as protein, rats fed casein or whey protein, a major component of
      milk, displayed a delayed onset of stroke compared with rats fed soybean or egg
      white protein. Rats fed an amino acids diet containing the same amino acids
      composition as casein did not have a delay in the onset of stroke. Increasing
      dietary fats, including butter as well as beef tallow and cocoa butter, did not
      affect the onset of stroke. All diets did not affect blood pressure in the early
      stage. CONCLUSIONS: These data suggest that the inverse association between dairy
      food consumption and incidence of stroke in epidemiological studies is causal and
      that peptides in milk protein, but not fat, might be responsible for this effect.

PMID- 22156691
TI  - Dehydration in hospital-admitted stroke patients: detection, frequency, and
      association.
AB  - BACKGROUND AND PURPOSE: We aimed to determine the frequency of dehydration, risk
      factors, and associations with outcomes at hospital discharge after stroke.
      METHODS: We linked clinical data from stroke patients in 2 prospective hospital
      registers with routine blood urea and creatinine results. Dehydration was defined
      by a blood urea-to-creatinine ratio >80. RESULTS: Of 2591 patients registered,
      1606 (62%) were dehydrated at some point during their admission. Independent risk
      factors for dehydration included older age, female gender, total anterior
      circulation syndrome, and prescribed diuretics (all P<0.001). Patients with
      dehydration were significantly more likely be dead or dependent at hospital
      discharge than those without (chi(2)=170.5; degrees of freedom=2; P<0.0001).
      CONCLUSIONS: Dehydration is common and associated with poor outcomes. Further
      work is required to establish if these associations are causal and if preventing
      or treating dehydration improves outcomes.

PMID- 22156692
TI  - Vessel wall MRI to differentiate between reversible cerebral vasoconstriction
      syndrome and central nervous system vasculitis: preliminary results.
AB  - BACKGROUND AND PURPOSE: Prospective differentiation between reversible cerebral
      vasoconstriction syndrome and central nervous system vasculitis can be
      challenging. We hypothesized that high-resolution vessel wall MRI would
      demonstrate arterial wall enhancement in central nervous system vasculitis but
      not in reversible cerebral vasoconstriction syndrome. METHODS: We identified all
      patients with multifocal segmental narrowing of large intracranial arteries who
      had high-resolution vessel wall MRI and follow-up angiography at our institute
      over a 4-year period and performed a detailed chart review. RESULTS: Three
      patients lacked arterial wall enhancement, and these all had reversal of arterial
      narrowing within 3 months. Four patients demonstrated arterial wall enhancement,
      and these had persistent or progressive arterial narrowing at a median follow-up
      of 17 months (range, 6-36 months) with final diagnoses of central nervous system
      vasculitis (3) and cocaine vasculopathy (1). CONCLUSIONS: Preliminary results
      suggest that high-resolution contrast-enhanced vessel wall MRI may enable
      differentiation between reversible cerebral vasoconstriction syndrome and central
      nervous system vasculitis.

PMID- 22156693
TI  - Sleep apnea risk among mexican american and non-Hispanic white stroke survivors.
AB  - BACKGROUND AND PURPOSE: Sleep apnea is a modifiable independent stroke risk
      factor and is associated with poor stroke outcomes. Mexican Americans have a
      higher incidence of stroke than non-Hispanic whites. In a biethnic community, we
      sought to determine the frequency of screening, testing, and treatment of sleep
      apnea among stroke survivors and to compare self-perceived risk of sleep apnea
      with actual risk. METHODS: A survey was mailed to ischemic stroke survivors in
      the Brain Attack Surveillance in Corpus Christi (BASIC) project. The survey
      included the validated sleep apnea screening tool, the Berlin questionnaire, and
      queried the frequency of sleep apnea screening by symptoms, formal sleep testing,
      and treatment. Self-perceived risk and actual high risk of sleep apnea were
      compared using McNemar's test. RESULTS: Of the 193 respondents (49% response
      rate), 54% were Mexican American. Forty-eight percent of respondents had a high
      risk of sleep apnea based on the Berlin questionnaire, whereas only 19% thought
      they were likely to have sleep apnea (P<0.01). There was no difference in the
      proportion of respondents at high risk of sleep apnea between Mexican Americans
      and non-Hispanic whites (48% versus 51%, P=0.73). Less than 20% of respondents
      had undergone sleep apnea screening, testing, or treatment. CONCLUSIONS: Stroke
      survivors perceive their risk of sleep apnea to be lower than their actual risk.
      Despite a significant proportion of both Mexican American and non-Hispanic white
      stroke survivors at high risk of sleep apnea, few undergo symptom screening,
      testing, or treatment. Both stroke survivors and physicians may benefit from
      educational interventions.

PMID- 22156694
TI  - Towards a consensus-based classification of childhood arterial ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The implementation of uniform nomenclature and
      classification in adult arterial ischemic stroke (AIS) has been critical for
      defining outcomes and recurrence risks according to etiology and in developing
      risk-stratified treatments. In contrast, current classification and nomenclature
      in childhood AIS are often overlapping or contradictory. Our purpose was to
      develop a comprehensive consensus-based classification system for childhood AIS.
      METHODS: Using a modified-Delphi method, members of the International Pediatric
      Stroke Study (IPSS) developed the Childhood AIS Standardized Classification And
      Diagnostic Evaluation (CASCADE) criteria. Two groups of pediatric stroke
      specialists from the IPSS classified 7 test cases using 2 methods each: (1)
      classification typical of the individual clinician's current clinical practice;
      and (2) classification based on the CASCADE criteria. Group 1 underwent in-person
      training in the utilization of the CASCADE criteria. Group 2 classified the same
      cases via an online survey, including definitions but without training. Inter
      rater reliability (IRR) was assessed via multi-rater unweighted kappa-statistic.
      RESULTS: In Group 1 (with training), IRR was improved using CASCADE criteria
      (kappa=0.78, 95% CI=[0.49, 0.94]), compared with typical clinical practice
      (kappa=0.40, 95% CI=[0.11, 0.60]). In Group 2 (without training), IRR was lower
      than among trained raters (kappa=0.61, 95% CI=[0.29, 0.77]), but higher than
      current practice (kappa=0.23, 95% CI=[0.03, 0.36]). CONCLUSIONS: A new, consensus
      based classification system for childhood AIS, the CASCADE criteria, can be used
      to classify cases with good IRR. These preliminary findings suggest that the
      CASCADE criteria may be particularity useful in the setting of prospective
      multicenter studies in childhood-onset AIS, where standardized training of
      investigators is feasible.

PMID- 22156695
TI  - Variations in quality indicators of acute stroke care in 6 European countries:
      the European Implementation Score (EIS) Collaboration.
AB  - BACKGROUND AND PURPOSE: Quality indicators serve as standards of care by which
      performance of individual hospitals is measured. Although several audits for
      monitoring quality of stroke care have been established in Europe, there is
      currently no consensus on quality indicators for acute stroke care or for
      methodology for collecting information on these measures. METHODS: An up-to-date
      inventory on European stroke audits in place in 2006 was performed in the course
      of a project funded by the European Union (European Implementation Score
      Collaboration [EIS]). Two regional (Flanders, Belgium; Catalonia, Spain) and 4
      national (Germany, Scotland, Sweden, England/Wales/Northern Ireland) stroke
      audits took part. Between November 2009 and July 2010, 2 standardized surveys and
      a series of interviews were performed to determine characteristics, methods, and
      content of these quality initiatives. For quality purposes, all summarized
      information was validated by representatives of the respective audits. RESULTS:
      Overall, 123 quality indicators (91 process, 24 outcome, and 8 structural
      indicators) were identified. Anticoagulants in patients with atrial fibrillation
      and brain imaging were the only quality indicators used in all, whereas another
      13 indicators were used in at least 2 of the quality initiatives. Substantial
      variations were found across the audits in terms of the development process of
      quality indicators, inclusion criteria, participation, population coverage, data
      documentation, follow-ups, benchmarking, and feedback of results to participants.
      CONCLUSIONS: There is a huge variety in measuring performance of acute stroke
      care in Europe, hampering valid comparisons of acute stroke care. Common
      standards for defining quality indicators and collecting information required for
      these measures should be defined in Europe.

PMID- 22156696
TI  - Nanoerythropoietin is 10-times more effective than regular erythropoietin in
      neuroprotection in a neonatal rat model of hypoxia and ischemia.
AB  - BACKGROUND AND PURPOSE: Erythropoietin (EPO) has been demonstrated to possess
      significant neuroprotective effects in stroke. We determined if the nano-drug
      form of human recombinant EPO (PLGA-EPO nanoparticles [PLGA-EPO-NP]) can enhance
      neuroprotection at lower dosages versus human recombinant EPO (r-EPO). METHODS:
      Established neonatal rat model of unilateral ischemic stroke was used to compare
      r-EPO, PLGA-EPO-NP and phosphate-buffered saline, given by daily intraperitoneal
      injections, followed by infarction volume and Rotarod Performance Test
      assessment. RESULTS: PLGA-EPO-NP significantly reduced infarction volumes 72
      hours after injury compared with the same concentrations of r-EPO. Functional
      deficits were significantly reduced by 300 U/kg PLGA-EPO-NP versus controls, with
      deficit attenuation apparent at significantly lower dosages of PLGA-EPO-NP versus
      r-EPO. CONCLUSIONS: PLGA-EPO-NP is neuroprotective and beneficial against
      deficits after brain ischemia, at significantly reduced dosages versus r-EPO.

PMID- 22156697
TI  - Swallowing screens after acute stroke: a systematic review.
AB  - BACKGROUND AND PURPOSE: Swallowing screens after acute stroke identify those
      patients who do not need a formal swallowing evaluation and who can safely take
      food and medications by mouth. We conducted a systematic review to identify
      swallowing screening protocols that met basic requirements for reliability,
      validity, and feasibility. METHODS: We searched MEDLINE and supplemented results
      with references identified through other databases, journal tables of contents,
      and bibliographies. All relevant references were reviewed and evaluated with
      specific criteria. RESULTS: Of 35 protocols identified, 4 met basic quality
      criteria. These 4 had high sensitivities of >=87% and high negative predictive
      values of >=91% when a formal swallowing evaluation was used as the gold
      standard. Two protocols had greater sample sizes and more extensive reliability
      testing than the others. CONCLUSIONS: We identified only 4 swallowing screening
      protocols for patients with acute stroke that met basic criteria. Cost
      effectiveness of screening, including costs associated with false-positive
      results and impact of screening on morbidity, mortality, and length of hospital
      stay, requires elucidation.

PMID- 22156698
TI  - Can genes modify stroke outcome and by what mechanisms?

PMID- 22156699
TI  - Left atrial catheter ablation and ischemic stroke.
AB  - Left atrial catheter ablation (LACA) has become an established therapy to abolish
      drug-refractory symptomatic paroxysmal and persistent atrial fibrillation.
      Restoring sinus rhythm by LACA may help to prevent atrial fibrillation-related
      strokes, but presently there is no evidence from randomized clinical trials to
      support this notion. This review summarizes the current knowledge and
      uncertainties regarding LACA and procedure-related ischemic stroke. In fact, most
      patients who undergo LACA have a rather low annual stroke risk even when left
      untreated, whereas LACA imposes a risk of procedure-related stroke of ~0.5% to
      1%. In addition, LACA may cause cerebral microemboli, resulting in ischemic
      lesions. These cerebral lesions, detectable by high-resolution MRI, could
      contribute to neuropsychological deficits and cognitive dysfunction. Furthermore,
      recurrent atrial fibrillaton episodes can be detected up to years after LACA and
      might cause ischemic strokes, especially in those patients in whom therapeutic
      anticoagulation was discontinued. Further prospective multicenter trials are
      needed to identify procedure-dependent risk factors for stroke and to optimize
      postprocedural anticoagulation management.

PMID- 22156700
TI  - MoCA, ACE-R, and MMSE versus the National Institute of Neurological Disorders and
      Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization
      Standards Neuropsychological Battery after TIA and stroke.
AB  - BACKGROUND AND PURPOSE: The Montreal Cognitive Assessment (MoCA) and
      Addenbrooke's Cognitive Examination-Revised (ACE-R) are proposed as short
      cognitive tests for use after stroke, but there are few published validations
      against a neuropsychological battery. We studied the relationship between MoCA,
      ACE-R, Mini-Mental State Examination (MMSE) and mild cognitive impairment (MCI)
      in patients with cerebrovascular disease and mild cognitive impairment (MCI).
      METHODS: One hundred consecutive non-institutionalized patients had the MMSE,
      MoCA, ACE-R, and National Institute of Neurological Disorders and Stroke-Canadian
      Stroke Network Vascular Cognitive Impairment Harmonization Standards
      Neuropsychological Battery >= 1 year after transient ischemic attack or stroke in
      a population-based study. MCI was diagnosed using modified Petersen criteria in
      which subjective cognitive complaint is not required (equivalent to cognitive
      impairment-no dementia) and subtyped by number and type of cognitive domains
      affected. RESULTS: Among 91 nondemented subjects completing neuropsychological
      testing (mean/SD age, 73.4/11.6 years; 44% female; 56% stroke), 39 (42%) had MCI
      (amnestic multiple domain=10, nonamnestic multiple domain=9, nonamnestic single
      domain=19, amnestic single domain=1). Sensitivity and specificity for MCI were
      optimal with MoCA <25 (sensitivity=77%, specificity=83%) and ACE-R <94
      (sensitivity=83%, specificity=73%). Both tests detected amnestic MCI better than
      nonamnestic single-domain impairment. MMSE only achieved sensitivity >70% at a
      cutoff of <29, mainly due to relative insensitivity to single-domain impairment.
      CONCLUSIONS: The MoCA and ACE-R had good sensitivity and specificity for MCI
      defined using the Neurological Disorders and Stroke-Canadian Stroke Network
      Vascular Cognitive Impairment Battery >=1 year after transient ischemic attack
      and stroke, whereas the MMSE showed a ceiling effect. However, optimal cutoffs
      will depend on use for screening (high sensitivity) or diagnosis (high
      specificity). Lack of timed measures of processing speed may explain the relative
      insensitivity of the MoCA and ACE-R to single nonmemory domain impairment.

PMID- 22156701
TI  - The safety of intravenous thrombolysis for ischemic stroke in patients with pre
      existing cerebral aneurysms: a case series and review of the literature.
AB  - BACKGROUND AND PURPOSE: Unruptured cerebral aneurysms are currently considered a
      contraindication to intravenous tissue-type plasminogen activator for acute
      ischemic stroke. This is due to a theoretical increase in the risk of hemorrhage
      from aneurysm rupture, although it is unknown whether this risk is a significant
      one. We sought to determine the safety of intravenous tissue-type plasminogen
      activator administration in a cohort of patients with pre-existing aneurysms.
      METHODS: We reviewed the medical records of patients treated for acute ischemic
      stroke with intravenous tissue-type plasminogen activator during an 11-year
      period at 2 academic medical centers. We identified a subset of patients with
      unruptured cerebral aneurysms present on prethrombolysis vascular imaging. Our
      outcomes of interest were any intracranial hemorrhage, symptomatic intracranial
      hemorrhage, and subarachnoid hemorrhage. Fisher exact test was used to compare
      the rates of hemorrhage among patients with and without aneurysms. RESULTS: We
      identified 236 eligible patients, of whom 22 had unruptured cerebral aneurysms.
      The rate of intracranial hemorrhage among patients with aneurysms (14%; 95% CI,
      3%-35%) did not significantly differ from the rate among patients without
      aneurysms (19%; 95% CI, 14%-25%). None of the patients with aneurysms developed
      symptomatic intracranial hemorrhage (0%; 95% CI, 0%-15%) compared with 10 of 214
      patients without aneurysms (5%; 95% CI, 2%-8%). Similar proportions of patients
      developed subarachnoid hemorrhage (5%; 95% CI, 0%-23% versus 6%; 95% CI, 3%-10%).
      CONCLUSIONS: Our findings suggest that intravenous tissue-type plasminogen
      activator for acute ischemic stroke is safe to administer in patients with pre
      existing cerebral aneurysms because the risk of aneurysm rupture and symptomatic
      intracranial hemorrhage is low.

PMID- 22156702
TI  - Does helicopter emergency medical service transfer offer benefit to patients with
      stroke?
AB  - BACKGROUND AND PURPOSE: Helicopter transportation of patients with acute stroke
      who have received recombinant tissue-type plasminogen activator is commonly
      considered the best option. We evaluated if transportation by helicopter can
      reduce complications and improve clinical outcomes in patients with acute stroke.
      METHODS: We conducted a review of consecutive patients with acute ischemic stroke
      transferred to our hospital after intravenous thrombolysis initiated at a
      referral center. RESULTS: A total of 122 patient transportations were analyzed,
      94 by air and 28 by ground. Time from activation of the transport system to
      arrival at our hospital was significantly shorter with air transportation (53
      versus 68 minutes, P=0.04). Two complications were noted in the air group and no
      complications were noted in the ground group (P=1.0). All other outcome measures
      were not significantly different between groups. CONCLUSIONS: Air transfer of
      patients with acute ischemic stroke treated with thrombolysis does not seem to
      impart any benefit to patient outcomes when compared with ground transport.
      Therefore, ground transport should be considered for these patients unless they
      are being considered for emergency endovascular rescue therapy.

PMID- 22156703
TI  - Conventional and anti-erosion fluoride toothpastes: effect on enamel erosion and
      erosion-abrasion.
AB  - New toothpastes with anti-erosion claims are marketed, but little is known about
      their effectiveness. This study investigates these products in comparison with
      various conventional NaF toothpastes and tin-containing products with respect to
      their erosion protection/abrasion prevention properties. In experiment 1, samples
      were demineralised (10 days, 6 * 2 min/day; citric acid, pH 2.4), exposed to
      toothpaste slurries (2 * 2 min/day) and intermittently stored in a mineral salt
      solution. In experiment 2, samples were additionally brushed for 15 s during the
      slurry immersion time. Study products were 8 conventional NaF toothpastes (1,400
      1,490 ppm F), 4 formulations with anti-erosion claims (2 F toothpastes: NaF +
      KNO(3) and NaF + hydroxyapatite; and 2 F-free toothpastes: zinc-carbonate
      hydroxyapatite, and chitosan) and 2 Sn-containing products (toothpaste: 3,436 ppm
      Sn, 1,450 ppm F as SnF(2)/NaF; gel: 970 ppm F, 3,030 ppm Sn as SnF(2)). A mouth
      rinse (500 ppm F as AmF/NaF, 800 ppm Sn as SnCl(2)) was the positive control.
      Tissue loss was quantified profilometrically. In experiment 1, most NaF
      toothpastes and 1 F-free formulation reduced tissue loss significantly (between
      19 and 42%); the Sn-containing formulations were the most effective (toothpaste
      and gel 55 and 78% reduction, respectively). In experiment 2, only 4 NaF
      toothpastes revealed significant effects compared to the F-free control
      (reduction between 29 and 37%); the F-free special preparations and the Sn
      toothpaste had no significant effect. The Sn gel (reduction 75%) revealed the
      best result. Conventional NaF toothpastes reduced the erosive tissue loss, but
      had limited efficacy regarding the prevention of brushing abrasion. The special
      formulations were not superior, or were even less effective.

PMID- 22156704
TI  - Should central serous chorioretinopathy be added to the list of ocular side
      effects of phosphodiesterase 5 inhibitors?
AB  - INTRODUCTION: Rare cases of central serous chorioretinopathy (CSC) associated
      with the intake of sildenafil citrate have been reported, although CSC is not
      included in the list of phosphodiesterase 5 (PDE5) inhibitor side effects.
      MATERIALS AND METHODS: We present a review of the literature and 2 cases of CSC
      in 2 men taking PDE5 inhibitors (vardenafil and tadalafil) for erectile
      dysfunction. In both cases chorioretinopathy appeared after intake of the
      inhibitor, resolved once the latter was discontinued, reappeared when the
      inhibitor was restarted and resolved once again after the inhibitor had been
      discontinued for the second time. DISCUSSION: PDE5 inhibitors used for male
      erectile dysfunction have been associated with ocular side effects including lid
      edema, hyposphagma, photophobia, mydriasis, dyschromatopsia, and nonarteritic
      anterior ischemic optic neuropathy. CSC was previously described in patients
      taking sildenafil citrate. Very recently, a case of CSC after tadalafil intake
      was reported. The relevant literature is reviewed and possible pathophysiologic
      mechanisms are discussed. CONCLUSION: The 2 presented cases of CSC after intake
      of vardenafil or tadalafil with positive dechallenge, rechallenge and second
      dechallenge reactions provide important arguments for considering CSC as a rare
      PDE5 inhibitor class-specific side effect.

PMID- 22156705
TI  - Alcohol use disorders among patients examined in emergency departments after a
      suicide attempt.
AB  - AIM OF THE STUDY: To assess the prevalence of alcohol use disorders (AUD) in a
      population of patients examined following attempted suicide and compare suicide
      attempts with and without AUD. METHODS: 180 patients examined in an emergency
      department after a suicide attempt were compared with 180 controls paired for sex
      and age. All patients answered the CAGE and the Fagerstrom questionnaire. The DSM
      IV-R criteria for alcohol, nicotine and cannabis abuse and dependence, as well as
      for borderline and antisocial personality, were checked. RESULTS: The prevalence
      of AUD was 43% among suicide attempters. Suicide attempters with AUD were more
      often men (52 vs. 30%), living alone (64 vs. 31%) and older (35.9 vs. 32.3
      years). They were more often dependent on nicotine (87 vs. 43%) and smoked more
      cannabis joints (1.4 vs. 0.5). They had taken alcohol before committing suicide
      more often (61 vs. 23%) and had more previous suicide attempts (2.5 vs. 0.9).
      Additionally, suicide attempters had higher scores of sensation seeking and
      presented more often with an antisocial or borderline personality. CONCLUSION:
      43% of the patients examined after a suicide attempt presented with AUD.
      Emergency units may provide an opportunity to identify their dependence disorder
      and offer information and treatment.

PMID- 22156706
TI  - Prevalence and markers of advanced liver disease in type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes is a risk factor for progression of non-alcoholic
      fatty liver disease (NAFLD) to fibrosis and cirrhosis. We examined the prevalence
      of advanced liver disease in people with type 2 diabetes and analysed the
      effectiveness of liver function tests (LFTs) as a screening tool. METHODS:
      Participants (n = 939, aged 61-76 years) from the Edinburgh Type 2 Diabetes
      Study, a randomly selected population of people with type 2 diabetes, underwent
      abdominal ultrasonography. Hyaluronic acid (HA) and platelet count/spleen
      diameter ratio (PSR) were used as non-invasive markers of hepatic fibrosis and
      portal hypertension. Subjects were screened for secondary causes of liver disease
      that excluded them from a diagnosis of NAFLD. The efficacy of LFTs [alanine
      aminotransferase (ALT) and gamma-glutamyltransferase (GGT)] in screening for
      liver disease was determined. RESULTS: Cirrhosis was identified by ultrasound in
      four participants (0.4%). Ten (1.1%) had evidence of portal hypertension (PSR <
      909), and two (0.2%) had hepatocellular carcinoma. Fifty-three participants
      (5.7%) had evidence of hepatic fibrosis (HA > 100 ng/ml in the absence of joint
      disease); a further 169 had HA > 50 ng/ml. In participants with NAFLD-related
      fibrosis (HA > 100 ng/ml), 12.5% had an elevated ALT level and 17.5% had an
      elevated GGT level. CONCLUSION: The prevalence of hepatic fibrosis and cirrhosis
      were lower than expected. The use of LFTs to screen for liver disease missed most
      cases of fibrosis predicted by raised HA levels.

PMID- 22156707
TI  - White matter abnormalities in primary Sjogren syndrome.
AB  - OBJECTIVE: To describe the main characteristics of patients with primary Sjogren
      syndrome (SS) and white matter abnormalities (WMA) seen by a specialist SS unit.
      METHODS: The study cohort included 321 consecutive patients fulfilling the 2002
      classification criteria for primary SS. We retrospectively analyzed the results
      of neuroimaging studies performed in patients who presented with neurological
      symptoms. Patients were further evaluated by three neurologists to determine
      fulfillment of the McDonald criteria for the diagnosis of multiple sclerosis
      (MS). RESULTS: Fifty-one (16%) patients had at least one neuroimaging study, and
      25 of these had WMA. WMA were classified as vascular pathological changes in 21
      patients: 10 had multiple small focal lesions, 7 had beginning confluence of
      lesions and 4 had diffuse involvement of the entire region. WMA were classified
      as inflammatory/demyelinating lesions (MS-like) in 4 patients who fulfilled the
      MRI Barkhof criteria. Patients with inflammatory/demyelinating lesions were
      younger (53.7 vs. 73.5 years, P = 0.001) and had a lower frequency of
      hypertension (25% vs. 86%, P = 0.031) and altered glomerular filtration rate (0%
      vs. 70%, P = 0.047) in comparison with patients with vascular lesions. The
      multivariate age-sex adjusted model including the seven variables which were
      statistically significant in the univariate analysis (antimalarial therapy,
      leukopenia, anti-La/SSB antibodies, diabetes, hypertension, metabolic syndrome
      and HDL-c levels) identified hypertension (P = 0.019) and HDL-c levels (P =
      0.032) as independent predictors of WMA in primary SS patients. CONCLUSION:
      Neuroimaging studies disclosed WMA in 49% of patients with primary SS and
      suspected neurological involvement. WMA were identified as vascular pathological
      changes in 80% of the patients, and hypertension and HDL-c levels as predictive
      factors for this association.

PMID- 22156708
TI  - Psychiatric pharmacotherapy update.

PMID- 22156709
TI  - Asenapine: a new antipsychotic option.
AB  - Asenapine is a new psychopharmacologic agent approved for the acute and
      maintenance treatment of schizophrenia and the acute and maintenance treatment of
      manic and mixed episodes associated with bipolar I disorder. The efficacy of
      asenapine in treating schizophrenia was evaluated in four 6-week studies in which
      placebo and active controls (risperidone, olanzapine, and haloperidol) were used.
      Two 3-week placebo-controlled trials examined the efficacy of asenapine and
      active control (olanzapine) in the treatment of bipolar I disorder. Asenapine
      demonstrated efficacy in relation to placebo for 2 of the acute schizophrenia
      trials and both trials examining the acute treatment of bipolar I disorder.
      Several factors should be examined when considering asenapine therapy in relation
      to other antipsychotics including efficacy, atypicality of receptor binding,
      obstacles to administration and compliance, and finally cost. No efficacy
      advantage is evident with asenapine over other antipsychotic agents. Barriers to
      achieving compliance with asenapine include the recommendations of twice daily
      dosing, the need to avoid food and liquids for at least 10 minutes
      postadministration, the need for patient cooperation with sublingual
      administration, and the low bioavailability of the tablet if swallowed. Finally,
      no cost advantage is evident for using asenapine in comparison to the already
      available generic risperidone or other soon-to-be generic atypical
      antipsychotics.

PMID- 22156710
TI  - A floating pharmacy on Lake Tanganyika.

PMID- 22156711
TI  - Hemorrhagic events lead to an increase in international normalized ratio in
      patients on warfarin.
AB  - PURPOSE: The purpose of this study was to support a theory that in a cohort of
      patients on warfarin with bleeding and an elevated international normalized ratio
      (INR), the INR elevation was related to the bleeding episode and not necessarily
      over anticoagulation from warfarin. METHODS: The medical records of patients
      taking warfarin who presented with a bleeding event and high INR were reviewed
      over an 18-month period. Data collected included warfarin dose, INR, and
      hematocrit 90 days before and after the bleeding event. Patients were interviewed
      to ascertain whether any interactions with warfarin occurred which could explain
      the high INR. RESULTS: Eighteen patients were identified who presented with
      bleeding, a high INR, and no identifiable reason for the elevated INR. A
      significant increase in INR was observed from baseline to the event (2.5 +/- 0.36
      vs 6.2 +/- 3.19; P = .0002), but the INR during all periods of follow-up did not
      differ from baseline (P = .35-.99). When compared with baseline, differences in
      the weekly warfarin dose reached statistical significance when all 12 weeks of
      follow-up were included (34 +/- 13.8 mg vs 32 +/- 15.5 mg; P = .01) but were not
      statistically significant when analyzed 4 to 12 weeks after the bleeding event.
      CONCLUSIONS: Our observations suggest that bleeding can result in an elevated INR
      in patients previously stable on warfarin.

PMID- 22156712
TI  - Masimo signal extraction technology pulse oximetry. Concerning the article by
      R.J. Rosychuk et al.: Discrepancies between arterial oxygen saturation and
      functional oxygen saturation measured with pulse oximetry in very preterm infants
      [Neonatology 2012;101:14-19].

PMID- 22156713
TI  - Grief, depressive symptoms, and physical health among recently bereaved spouses.
AB  - PURPOSE:  Widowhood is among the most distressing of all life events, resulting
      in both mental and physical health declines. This paper explores the dynamic
      relationship between physical health and psychological well-being among recently
      bereaved spouses.  DESIGN AND METHODS:  Using a sample of 328 bereaved persons
      who participated in the "Living After Loss" study, we modeled trends in physical
      health, somatic symptoms, and psychological well-being over the first year and a
      half of widowhood. The primary focus is whether physical health at the time of
      widowhood modifies psychological well-being over time.  RESULTS:  There were
      considerable somatic symptoms during the earliest months of bereavement but no
      major health declines over the first year and half of bereavement. Those in poor
      health had initially higher levels of grief and depressive symptoms, but the
      trajectories or changes over time were similar regardless of health status. Those
      with poor health at the time of widowhood had significantly higher risks of
      complicated grief and major depression disorder.  IMPLICATIONS:  Bereavement
      requires physical and emotional adjustment, but the psychological trajectory of
      bereavement may be somewhat universal. Bereavement support ought to include a
      focus on self-care and health promotion in addition to emotional support,
      especially because those with poor health initially may be most susceptible to
      prolonged and intense clinical distress.

PMID- 22156714
TI  - Paying for retirement: sex differences in inclusion in employer-provided
      retirement plans.
AB  - PURPOSE: This study examines sex differences among Baby Boom workers in the
      likelihood of coverage by an employer-provided retirement plan. DESIGN AND
      METHODS: This study used a sample of Baby Boom workers drawn from the 2009
      Current Population Survey. Independent variables were selected to replicate as
      closely as possible those in two 1995 studies of retired workers and pension
      plans. Three new variables were added to reflect major social and economic shifts
      since 1995. Logistic regression was performed to analyze the effect of the
      independent variables on the likelihood of retirement plan coverage. RESULTS: In
      this cohort, the proportions of men and women included in employer-provided
      retirement plans were almost the same. The overall odds of women being included
      in a plan were only slightly less than even and in certain cases were
      significantly higher than the odds for men. Predictors of inclusion that were
      most important for both women and men were minority status, employment in a core
      industry or in a government position, educational level, and marital status.
      IMPLICATIONS: Although a much larger group of workers is included in retirement
      plans than in previous studies, and Baby Boom women are less disadvantaged in
      this regard than women in earlier studies, minority and immigrant workers
      continue to be disadvantaged, and the security of government retirement plans may
      be weakening with current economic difficulties.

PMID- 22156715
TI  - Factor structure of the Korean version of Wong and Law's Emotional Intelligence
      Scale.
AB  - This study reports the factor structure of a Korean version of the 16-item Wong
      and Law Emotional Intelligence Scale (WLEIS) for a sample of 161 Korean
      university students. Confirmatory factor analysis supported the four-factor model
      of the WLEIS: (1) self-emotional appraisal, (2) others' emotional appraisal, (3)
      use of emotion, and (4) regulation of emotion. However, improvement of the model
      fit after removing three items suggests the need for future research on the cross
      cultural measurement invariance of the WLEIS.

PMID- 22156716
TI  - Is the Narcissistic Personality Inventory still relevant? A test of independent
      grandiosity and entitlement scales in the assessment of narcissism.
AB  - Some scholars have called for the replacement of the Narcissistic Personality
      Inventory (NPI) with more narrow scales measuring grandiosity and entitlement
      instead. In the current study, the authors examined the relations among the NPI
      and measures of grandiosity and entitlement, as well as in relation to a measure
      of the Five-Factor Model (FFM). The NPI manifested significant correlations with
      the alternative scales of entitlement and grandiosity and relatively similar
      patterns of correlations with the FFM traits. Of note, the NPI manifested
      significant incremental validity in the prediction of several FFM traits that are
      central to the conceptualization of narcissism. These findings suggest that some
      caution must be used before assuming that these lower-order scales can be used to
      replace the NPI in the assessment of narcissism.

PMID- 22156717
TI  - Construct validity of the Anxiety Sensitivity Index-3 in clinical samples.
AB  - Using two clinical samples of patients, the presented studies examined the
      construct validity of the recently revised Anxiety Sensitivity Index-3 (ASI-3).
      Confirmatory factor analyses established a clear three-factor structure that
      corresponds to the postulated subdivision of the construct into correlated
      somatic, social, and cognitive components. Participants with different primary
      clinical diagnoses differed from each other on the ASI-3 subscales in
      theoretically meaningful ways. Specifically, the ASI-3 successfully discriminated
      patients with anxiety disorders from patients with nonanxiety disorders.
      Moreover, patients with panic disorder or agoraphobia manifested more somatic
      concerns than patients with other anxiety disorders and patients with nonanxiety
      disorders. Finally, correlations of the ASI-3 scales with other measures of
      clinical symptoms and negative affect substantiated convergent and discriminant
      validity. Substantial positive correlations were found between the ASI-3 Somatic
      Concerns and body vigilance, between Social Concerns and fear of negative
      evaluation and socially inhibited behavior, and between Cognitive Concerns and
      depression symptoms, anxiety, fear of negative evaluation, and subjective
      complaints. Moreover, Social Concerns correlated negatively with dominant and
      intrusive behavior. Results are discussed with respect to the contribution of the
      ASI-3 to the assessment of anxiety-related disorders.

PMID- 22156718
TI  - Diagnostic construct validity of MMPI-2 Restructured Form (MMPI-2-RF) scale
      scores.
AB  - In the current investigation, the authors examined the diagnostic construct
      validity of the Minnesota Multiphasic Personality Inventory-2-Restructured Form
      (MMPI-2-RF) in a patient sample. All participants were diagnosed via the
      Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P). The data
      set used in this study was composed of 544 patients--67 with bipolar disorder,
      407 with major depressive disorder, and 70 with schizophrenia. Multivariate
      analyses revealed a pattern of mean scale differences among patient groups that
      was mostly consistent with the prominent features of each diagnostic group;
      logistic regression analyses identified a number of scales that were strong,
      unique predictors in the differentiation between pairs of diagnostic groups. The
      higher order scales (H-O)--the Emotional/Internalizing Dysfunction (EID) and
      Thought Dysfunction (THD) scales were most useful in differentiating between
      patient groups. For differentiating bipolar disorder patients from the other
      diagnostic groups, the Activation (ACT) Specific Problem scale was most useful.
      Although not all hypothesized scale differences emerged; overall, the pattern of
      results provides support for the diagnostic construct validity of the MMPI-2-RF
      scales.

PMID- 22156719
TI  - The structure of women's mood in the early postpartum.
AB  - The "postpartum blues" is a mild, predictable mood disturbance occurring within
      the first several days following childbirth. Previous analyses of the "blues"
      symptom structure yielded inconclusive findings, making reliable assessment a
      significant methodological limitation. The current study aimed to explicate the
      symptom structure of women's mood following childbirth, and to examine
      psychometric properties of the Daily Experiences Questionnaire (DEQ), an adapted
      version of the Kennerley Blues Questionnaire that included additional items from
      the Positive and Negative Affect Schedule. Mothers who recently delivered (N =
      216) were recruited from a university hospital and asked to complete mood ratings
      on six consecutive days using the DEQ. Exploratory factor analysis yielded an
      interpretable two-factor solution identified as Negative Affect and Positive
      Affect. Scale reliability indices were excellent, with a high level of agreement
      in factor structure over time. This two-factor model provides reliable assessment
      of women's mood in the early postpartum, informing the study of reproductive
      related mood disorders.

PMID- 22156720
TI  - Integrating risk context into risk assessments: the Risk Context Scale.
AB  - The context in which offenders are released is an important component of
      conducting risk assessments. A sample of 257 supervised male parolees were
      followed in the community (M = 870 days) after an initial risk assessment.
      Drawing on community-based information, the purpose of this study was to evaluate
      the recently developed Risk Context Scale. Four domains from the Risk Context
      Scale include Resource Engagement, Social Network Presence, Integration of Care,
      and Social Stability. Using mediation analysis, an initial static risk
      probability was altered up to 26% by accounting for risk context. Implications of
      the present results include a broader explanation of recidivism, offering
      intervention strategies, and further individualizing risk assessments.

PMID- 22156721
TI  - Reliable Digit Span: a systematic review and cross-validation study.
AB  - Reliable Digit Span (RDS) is a heavily researched symptom validity test with a
      recent literature review yielding more than 20 studies ranging in dates from 1994
      to 2011. Unfortunately, limitations within some of the research minimize clinical
      generalizability. This systematic review and cross-validation study was conducted
      to address these limitations, thus increasing the measure's clinical utility.
      Sensitivity and specificity rates were calculated for the <=6 and <=7 cutoffs
      when data were globally combined and divided by clinical groups. The cross
      validation of specific diagnostic groups was consistent with the data reported in
      the literature. Overall, caution should be used when utilizing the <=7 cutoff in
      all clinical groups and when utilizing the <=6 cutoff in the following groups:
      cerebrovascular accident, severe memory disorders, mental retardation, borderline
      intellectual functioning, and English as a second language. Additional
      limitations and cautions are provided.

PMID- 22156722
TI  - Increased anterior cingulate cortex and hippocampus activation in Complex PTSD
      during encoding of negative words.
AB  - Post-traumatic stress disorder (PTSD) is associated with impaired memory
      performance coupled with functional changes in brain areas involved in
      declarative memory and emotion regulation. It is not yet clear how symptom
      severity and comorbidity affect neurocognitive functioning in PTSD. We performed
      a functional magnetic resonance imaging (fMRI) study with an emotional
      declarative memory task in 28 Complex PTSD patients with comorbid depressive and
      personality disorders, and 21 healthy non-trauma-exposed controls. In Complex
      PTSD patients--compared to controls--encoding of later remembered negative words
      vs baseline was associated with increased blood oxygenation level dependent
      (BOLD) response in the left ventral anterior cingulate cortex (ACC) and dorsal
      ACC extending to the dorsomedial prefrontal cortex (dmPFC) together with a trend
      for increased left hippocampus activation. Patients tended to commit more False
      Alarms to negative words compared to controls, which was associated with enhanced
      left ventrolateral prefrontal and orbitofrontal cortex (vlPFC/OFC) responses.
      Severity of child abuse was positively correlated with left ventral ACC activity
      and severity of depression with (para) hippocampal and ventral ACC activity.
      Presented results demonstrate functional abnormalities in Complex PTSD in the
      frontolimbic brain circuit also implicated in fear conditioning models, but
      generally in the opposite direction, which may be explained by severity of the
      trauma and severity of comorbid depression in Complex PTSD.

PMID- 22156723
TI  - Can we share the joy of others? Empathic neural responses to distress vs joy.
AB  - The neural bases of empathy have been examined mainly in the context of reacting
      to others' distress, while almost no attention has been paid to the mechanisms by
      which we share others' joy. Using functional magnetic resonance imaging, we
      demonstrated that the same neural network mediates judgment of the emotional
      state of the other in response to both negative and positive events through
      empathy-related structures, such as the medial prefrontal cortex (MPFC), the
      insula, the superior temporal sulcus (STS) and the inferior frontal gyrus (IFG).
      However, the responses of the MPFC, bilateral insula and the right IFG to
      negative experiences occurring to the other (but not to the self) were found to
      be much more intense than the responses to positive experiences, indicating that
      humans have a remarkable ability to share the distress of others, but may react
      less to the joy of others.

PMID- 22156724
TI  - Influence of maternal dental anxiety on the child's dental caries experience.
AB  - This study assessed the influence of maternal dental anxiety-related behavior on
      the child's caries experience. A cross-sectional study with 608 mother-child
      dyads during the Children's National Immunization Campaign in Pelotas, Brazil was
      performed. Mothers were asked to answer a questionnaire and dental examination of
      the children was performed (dmft). The association assessment used Poisson
      regression. Children from anxious mothers were more likely to present untreated
      caries even after covariate adjustment. Boys, older children and low-income
      family children presented a higher dmft mean. Preventive strategies should focus
      not only on child and family characteristics, but also on maternal dental anxiety
      related behaviors.

PMID- 22156725
TI  - Psoriasis patients with nail disease have a greater magnitude of underlying
      systemic subclinical enthesopathy than those with normal nails.
AB  - OBJECTIVE: Enthesopathy is a major feature of psoriatic arthritis (PsA), which is
      supported by imaging studies. Given that nail disease often predates PsA and that
      the nail is directly anchored to entheses, the authors asked whether nail
      involvement in psoriasis equates with a systemic enthesopathy. METHODS: Forty-six
      patients with psoriasis (31 with nail disease) and 21 matched healthy controls
      (HC) were recruited. 804 entheses of upper and lower limbs were scanned by an
      ultrasonographer blinded to clinical details. RESULTS: Psoriasis patients had
      higher enthesitis scores than HC (median (range) 21 (0-65) vs 11 (3-39),
      p=0.005). Enthesopathy scores were higher in patients with nail disease (23 (0
      65)) than in patients without nail disease (15 (5-26), p=0.02) and HC (11 (3-39),
      p=0.003). Inflammation scores of patients with nail disease (13 (0-34)) were
      higher than patients without nail disease (8 (2-15), p=0.02) and HC (5 (0-19),
      p<0.001). Modified nail psoriasis severity index scores were correlated to both
      inflammation (r(2)=0.45, p=0.005) and chronicity scores (r(2)=0.35, p=0.04). No
      link between the psoriasis area and severity index and enthesitis was evident.
      CONCLUSION: The link between nail disease and contemporaneous subclinical
      enthesopathy offers a novel anatomical basis for the predictive value of nail
      psoriasis for PsA evolution.

PMID- 22156727
TI  - Long-term structural and functional outcomes of therapy in juvenile-onset primary
      open-angle glaucoma: a five-year follow-up.
AB  - OBJECTIVE: To evaluate long-term structural and functional changes of the optic
      nerve head in medically and surgically treated juvenile-onset primary open-angle
      glaucoma (JOAG). METHODS: Forty-two eyes of 42 consecutive primary JOAG patients
      presenting between January 2000 and January 2003. Results were analysed for long
      term intra-ocular pressure (IOP) control, IOP fluctuation, disc characteristics
      on a Heidelberg Retinal Tomograph II and for visual field changes over a 5-year
      period. The parameters were compared between medically and surgically treated
      eyes. RESULTS: The average age of the patients was 26.8 +/- 6.1 years. The
      average baseline IOP was 35.3 +/- 14.9 mm Hg. An IOP control <18 mm Hg was
      achieved in 84% of eyes that underwent filtering surgery (n = 17), compared to
      63% on medical therapy alone (n = 25) at the end of 5 years; log rank test p =
      0.38. Over 5 years, 4 eyes showed progression (9.5%) of which 3 had been
      medically treated and 1 had failed surgery (p = 0.45). CONCLUSION: A tenth of
      JOAG eyes showed progression over 5 years, and this was more common in those
      treated medically. Aggressive IOP lowering may thus be needed in eyes with JOAG.

PMID- 22156729
TI  - SUP35 expression is enhanced in yeast containing [ISP+], a prion form of the
      transcriptional regulator Sfp1.
AB  - [ISP+] is a prion form of the global transcriptional regulator Sfp1 in
      Saccharomyces cerevisiae that manifests phenotypically as an antisuppressor of
      specific sup35 nonsense suppressor mutations. Although SUP35 is a Sfp1 target,
      the mechanism of antisuppression is unclear. Here we show that the level of SUP35
      transcription in [ISP+] cells containing the sup35 mutation is increased relative
      to [isp-] cells and cells with a SFP1 deletion. As a result, [ISP+] cells have
      increased amounts of Sup35 encoded by the mutant allele. Indeed, additional
      experiments showed that increased amounts of mutant Sup35 may cause
      antisuppression. Remarkably, [ISP+] effects are not equivalent to those produced
      by SFP1 deletion, so [ISP+] represents an obvious example of a functionally
      active prion form of a protein. This feature distinguishes [ISP+] from other
      yeast prions, where prion switch often has the same effect as inactivation of a
      prion host gene. We suggest that enhancement of SUP35 expression in [ISP+] cells
      is caused by specific interaction of Sfp1 in its prion form with some negative
      SUP35 regulator. We also demonstrate that the advantage of [ISP+] strains over
      [isp-] strains described in our earlier work is specific for certain genetic
      background and growth conditions.

PMID- 22156728
TI  - E. coli chaperones DnaK, Hsp33 and Spy inhibit bacterial functional amyloid
      assembly.
AB  - Amyloid formation is an ordered aggregation process, where beta-sheet rich
      polymers are assembled from unstructured or partially folded monomers. We
      examined how two Escherichia coli cytosolic chaperones, DnaK and Hsp33, and a
      more recently characterized periplasmic chaperone, Spy, modulate the aggregation
      of a functional amyloid protein, CsgA. We found that DnaK, the Hsp70 homologue in
      E. coli, and Hsp33, a redox-regulated holdase, potently inhibited CsgA
      amyloidogenesis. The Hsp33 anti-amyloidogenesis activity was oxidation dependent,
      as oxidized Hsp33 was significantly more efficient than reduced Hsp33 at
      preventing CsgA aggregation. When soluble CsgA was seeded with preformed amyloid
      fibers, neither Hsp33 nor DnaK were able to efficiently prevent soluble CsgA from
      adopting the amyloid conformation. Moreover, both DnaK and Hsp33 increased the
      time that CsgA was reactive with the amyloid oligomer conformation-specific A11
      antibody. Since CsgA must also pass through the periplasm during secretion, we
      assessed the ability of the periplasmic chaperone Spy to inhibit CsgA
      polymerization. Like DnaK and Hsp33, Spy also inhibited CsgA polymerization in
      vitro. Overexpression of Spy resulted in increased chaperone activity in
      periplasmic extracts and in reduced curli biogenesis in vivo. We propose that
      DnaK, Hsp33 and Spy exert their effects during the nucleation stages of CsgA
      fibrillation. Thus, both housekeeping and stress induced cytosolic and
      periplasmic chaperones may be involved in discouraging premature CsgA
      interactions during curli biogenesis.

PMID- 22156726
TI  - Advances in omics and bioinformatics tools for systems analyses of plant
      functions.
AB  - Omics and bioinformatics are essential to understanding the molecular systems
      that underlie various plant functions. Recent game-changing sequencing
      technologies have revitalized sequencing approaches in genomics and have produced
      opportunities for various emerging analytical applications. Driven by
      technological advances, several new omics layers such as the interactome,
      epigenome and hormonome have emerged. Furthermore, in several plant species, the
      development of omics resources has progressed to address particular biological
      properties of individual species. Integration of knowledge from omics-based
      research is an emerging issue as researchers seek to identify significance, gain
      biological insights and promote translational research. From these perspectives,
      we provide this review of the emerging aspects of plant systems research based on
      omics and bioinformatics analyses together with their associated resources and
      technological advances.

PMID- 22156730
TI  - A bipolar personality of yeast prion proteins.
AB  - Prions are infectious, self-propagating protein conformations. [PSI+], [RNQ+] and
      [URE3] are well characterized prions in Saccharomyces cerevisiae and represent
      the aggregated states of the translation termination factor Sup35, a functionally
      unknown protein Rnq1, and a regulator of nitrogen metabolism Ure2, respectively.
      Overproduction of Sup35 induces the de novo appearance of the [PSI+] prion in
      [RNQ+] or [URE3] strain, but not in non-prion strain. However, [RNQ+] and [URE3]
      prions themselves, as well as overexpression of a mutant Rnq1 protein,
      Rnq1Delta100, and Lsm4, hamper the maintenance of [PSI+]. These findings point to
      a bipolar activity of [RNQ+], [URE3], Rnq1Delta100, and Lsm4, and probably other
      yeast prion proteins as well, for the fate of [PSI+] prion. Possible mechanisms
      underlying the apparent bipolar activity of yeast prions will be discussed.

PMID- 22156731
TI  - The complexity and implications of yeast prion domains.
AB  - Prions are infectious proteins with altered conformations converted from
      otherwise normal host proteins. While there is only one known mammalian prion
      protein, PrP, a handful of prion proteins have been identified in the yeast
      Saccharomyces cerevisiae. Yeast prion proteins usually have a defined region
      called prion domain (PrD) essential for prion properties, which are typically
      rich in glutamine (Q) and asparagine (N). Despite sharing several common
      features, individual yeast PrDs are generally intricate and divergent in their
      compositional characteristics, which potentially implicates their prion
      phenotypes, such as prion-mediated transcriptional regulations.

PMID- 22156732
TI  - Influence of prion variant and yeast strain variation on prion-molecular
      chaperone requirements.
AB  - Prions of budding yeast serve as a tractable model of amyloid behavior. Here we
      address the issue of the effect of yeast strain variation on prion stability,
      focusing also on the effect of amyloid conformation and the involvement of the co
      chaperone Sis1, an essential J-protein partner of Hsp70. We found, despite an
      initial report to the contrary, that yeast strain background has little effect on
      the requirement for particular Sis1 domains for stable propagation of the prion
      [RNQ+], if the level of Sis1 expression is controlled. On the other hand, some
      variation in prion behavior was observed between yeast strains, in particular,
      the stability of certain [PSI+] variants. Future examination of such yeast strain
      specific phenomena may provide useful insights into the basis of prion/chaperone
      dynamics.

PMID- 22156733
TI  - Weighed, measured, and still searching: bevacizumab in the treatment of
      unselected patients with advanced breast cancer.

PMID- 22156734
TI  - The perceptions, social determinants, and negative health outcomes associated
      with depressive symptoms among U.S. Chinese older adults.
AB  - PURPOSE OF THE STUDY: Recent demographic growth of the U.S. Chinese aging
      population calls for comprehensive understanding of their unique health needs.
      The objective of this study is to examine the perceptions, social determinants of
      depressive symptoms as well as their impact on health and well-being in a
      community-dwelling U.S. Chinese aging population in Chicago. DESIGN AND METHODS:
      A community-based participatory research approach was implemented to partner with
      the Chicago Chinatown population in a geographically defined community. Data were
      collected from questionnaires and semistructured focus group interviews with 78
      community-dwelling Chinese older adults. RESULTS: Our findings suggest that the
      depressive symptoms were common among older adults. It was frequently identified
      through feelings of helplessness, feelings of dissatisfaction with life, feelings
      of getting bored, loss of interests in activities, suicidal ideation, and
      feelings of worthlessness. Societal conflicts, family conflicts, financial
      constraints, personality, and worsening physical health may be associated with
      greater depressive symptoms. In addition, depressive symptoms may be detrimental
      to the overall health and well-being of Chinese older adults. IMPLICATIONS: This
      study has wide implications for health care professionals, social services
      agencies, and policy makers. Our results call for improved public health
      education and awareness programs to highlight the health impact of depressive
      symptoms on Chinese older adults. Future prospective studies are needed to
      investigate the prevalence of depressive symptoms among U.S. Chinese older
      adults. Longitudinal research is needed to quantify the risk and protective
      factors of depressive symptoms.

PMID- 22156736
TI  - The statin-low cholesterol-cancer conundrum.

PMID- 22156737
TI  - The brainstem is at high risk for recurrent noncardioembolic cerebral infarction
      in association with diabetes mellitus: a hospital-based study.
AB  - The goals of the study were to investigate the importance of brainstem infarction
      (BSI) in recurrent noncardioembolic ischemic stroke and to examine the relevant
      clinical background. Data were retrospectively reviewed for 655 consecutive
      patients with acute noncardioembolic infarction who were admitted to our hospital
      from January 2004 to August 2010. The patients were divided into first-stroke (n
      = 592) and recurrent-stroke (n = 63) groups. Acute infarcted lesions were
      explored on MRI, and clinical background factors including age, sex, smoking,
      atrial fibrillation, coronary heart disease, hypertension, hyperlipidemia and
      diabetes mellitus (DM) were assessed. The frequency of BSI in the recurrent
      stroke group was significantly higher than that in first-stroke patients (30.2
      vs. 14.9%, p = 0.0033). No other clinical background factors differed between the
      two groups. Only the frequency of DM differed significantly among four subgroups
      formed based on stroke recurrence and BSI (p < 0.0001): DM was present in 63.2%
      of recurrent-stroke patients with BSI, 54.5% of first-stroke patients with BSI,
      27.4% of first-stroke patients without BSI, and 20.5% of recurrent-stroke
      patients without BSI. We conclude that the brainstem is at high risk for
      recurrent cerebral infarction in patients with DM.

PMID- 22156738
TI  - In vivo measurements of tooth wear over 12 months.
AB  - The aim of this study was to measure the progression of tooth wear in a cohort of
      63 patients, 43 males and 20 females with a mean age of 39.1 years. Recruitment
      followed referral from general practice to Guy's Hospital for advice/management
      of tooth wear. Addition silicone impressions were taken at 6-month intervals for
      a total of 12 months; impressions were subsequently poured in type IV gypsum.
      Casts were scanned using a non-contacting laser profilometer and then
      superimposed using Geomagic(r) Qualify 11. Wear was measured in MUm by tooth per
      time interval. A questionnaire highlighting dietary, parafunctional and gastric
      risk factors was obtained from each participant. Clustered multiple regression
      analysis was used to determine the relationship between tooth wear progression
      and risk factors. Maximum follow-up times were 6 months for 63 participants and
      12 months for 30 participants. The measurement error was 15 MUm. At the tooth
      level, 72.2% of 1,078 teeth wore <15 MUm over a 6-month period. At the subject
      level, 77.7% of 63 participants showed median wear <15 MUm over a 6-month period.
      There was a statistical trend towards tooth wear progression being associated
      with gastric risk factors (p < 0.05). The lower molars and the upper anterior
      teeth were the most commonly affected teeth; the lower molars and the upper
      central incisors were the most severely affected teeth. Tooth wear progression
      was slow in this cohort, suggesting that tooth wear may be cyclical and inactive
      in the majority of participants.

PMID- 22156739
TI  - Association of polymorphisms in angiotensin and aldosterone synthase genes of the
      renin-angiotensin-aldosterone system with high-altitude pulmonary edema.
AB  - Studies on different populations have suggested variability in individual
      susceptibility to altitude sickness depending on genetic makeup. The renin
      angiotensin-aldosterone system (RAAS) pathway plays a key role in regulation of
      vascular tone and circulatory homeostasis. The present study was undertaken to
      investigate the possible association of the RAAS in the development of high
      altitude pulmonary edema (HAPE) in lowlanders exposed to high altitude. Three
      categories of subjects were selected: individuals who developed HAPE on acute
      induction to high altitude (HAPE); individuals tolerant to high-altitude exposure
      who showed no symptoms of HAPE (resistant controls; rCON); and natives of high
      altitude (HAN). Genetic variants in the genes of the RAAS such as renin (REN),
      angiotensin (AGT), angiotensin-converting enzyme (ACE), aldosterone synthase
      (CYP11B2) and angiotensin II receptor type 1 (AGTR1) have been investigated. The
      T174M polymorphism in AGT showed a significant difference in HAPE and HAN and
      also HAN and controls. Also, genotyping in the CYP11B2 T-344C promoter region
      resulted in a significant difference between HAPE and HAN both at genotypic and
      allelic levels. The genotypic difference was statistically insignificant for the
      AGTR1 A1166C 3' UTR. The present investigation demonstrates a possible
      association between the polymorphisms existing in the RAAS pathway T174M and
      CYP11B2 C-344T and sensitivity of an individual to develop HAPE. The results also
      indicate the existence of ethnic variation between the HAN and the other two
      groups comprising lowlanders.

PMID- 22156740
TI  - Functional connectivity between amygdala and facial regions involved in
      recognition of facial threat.
AB  - The recognition of threatening faces is important for making social judgments.
      For example, threatening facial features of defendants could affect the decisions
      of jurors during a trial. Previous neuroimaging studies using faces of members of
      the general public have identified a pivotal role of the amygdala in perceiving
      threat. This functional magnetic resonance imaging study used face photographs of
      male prisoners who had been convicted of first-degree murder (MUR) as threatening
      facial stimuli. We compared the subjective ratings of MUR faces with those of
      control (CON) faces and examined how they were related to brain activation,
      particularly, the modulation of the functional connectivity between the amygdala
      and other brain regions. The MUR faces were perceived to be more threatening than
      the CON faces. The bilateral amygdala was shown to respond to both MUR and CON
      faces, but subtraction analysis revealed no significant difference between the
      two. Functional connectivity analysis indicated that the extent of connectivity
      between the left amygdala and the face-related regions (i.e. the superior
      temporal sulcus, inferior temporal gyrus and fusiform gyrus) was correlated with
      the subjective threat rating for the faces. We have demonstrated that the
      functional connectivity is modulated by vigilance for threatening facial
      features.

PMID- 22156741
TI  - Measuring genome instability in aging - a mini-review.
AB  - BACKGROUND: There is mounting evidence for an age-dependent accumulation of
      somatic mutations as a result of the inherent imperfection of DNA replication and
      repair. A possible age-related decline in genome maintenance systems may
      exacerbate this age-related loss of genome integrity. A review of the current
      methods of mutation detection is timely in view of the lack of insight as to the
      magnitude of somatic mutation accumulation, the types of mutations that
      accumulate, and their functional consequences. OBJECTIVE: In this paper we review
      the current methods for measuring genome instability in organisms during aging or
      in relation to life span. METHODS: The review is based on established and novel
      concepts from the existing literature, with some examples from our own
      laboratory. RESULTS: Studies using cytogenetic assays and endogenous or
      transgenic mutation reporter assays provide strong evidence for age-related
      increases of different types of mutations in animals and humans during aging.
      This increase in DNA mutations is tissue-specific and also differs between
      species. CONCLUSION: Today, our knowledge of somatic mutation profiles in aging
      is mainly derived from cytogenetics and the use of endogenous and transgenic
      mutation reporter assays. The emergence of new approaches, most notably massively
      parallel sequencing, will give us deeper insight into the nature of spontaneous
      genome instability and its possible causal relationship to aging and age-related
      disease.

PMID- 22156743
TI  - Ribosome biogenesis factors working with a nuclear envelope SUN domain protein:
      new players in the solar system.
AB  - The nucleolus, the most prominent structure observed in the nucleus, is often
      called a "ribosome factory." Cells spend an enormous fraction of their resources
      to achieve the mass-production of ribosomes required by rapid growth. On the
      other hand, ribosome biogenesis is also tightly controlled, and must be
      coordinated with other cellular processes. Ribosomal proteins and ribosome
      biogenesis factors are attractive candidates for this link. Recent results
      suggest that some of them have functions beyond ribosome biogenesis. Here we
      review recent progress on ribosome biogenesis factors, Ebp2 and Rrs1, in yeast
      Saccharomyces cerevisiae. In this organism, Ebp2 and Rrs1 are found in the
      nucleolus and at the nuclear periphery. At the nuclear envelope, these proteins
      interact with a membrane-spanning SUN domain protein, Mps3, and play roles in
      telomere clustering and silencing along with the silent information regulator
      Sir4. We propose that a protein complex consisting Ebp2, Rrs1 and Mps3 is
      involved in a wide range of activities at the nuclear envelope.

PMID- 22156744
TI  - UPF1: a leader at the end of chromosomes.
AB  - The human helicase and ATPase up-frameshift suppressor 1 (UPF1), traditionally
      known as a major player in several RNA quality control mechanisms, is emerging as
      a crucial caretaker of the stability of the genome. Work from my laboratory has
      provided insight into the function of UPF1 during DNA metabolism and has revealed
      that this versatile enzyme sustains the proper replication of telomeres, the
      protective structures located at the ends of linear eukaryotic chromosomes. We
      have supplied direct evidence that telomere replication is not completed in cells
      with compromised UPF1 function, leading to the accumulation of DNA damage and
      telomere abnormalities. We also have isolated a number of factors that physically
      interact with UPF1 and might represent molecular links between UPF1 and
      telomeres. In this paper, I re-evaluate the functions of UPF1 in maintaining the
      stability of telomeres and of the genome at large and suggest a model that
      explains how UPF1 might be recruited and function during telomere replication.

PMID- 22156746
TI  - Evolution of the lamin protein family: what introns can tell.
AB  - Lamins are the major components of the nuclear lamina, a filamentous layer found
      at the interphase between chromatin and the inner nuclear membrane. The lamina
      supports the nuclear envelope and provides anchorage sites for chromatin. Lamins
      and their associated proteins are required for most nuclear activities, mitosis,
      and for linking the nucleoskeleton to the network of cytoskeletal filaments.
      Mutations in lamins and their associated proteins give rise to a wide range of
      diseases, collectively called laminopathies. This review focuses on the evolution
      of the lamin protein family. Evolution from basal metazoans to man will be
      described on the basis of protein sequence comparisons and analyses of their gene
      structure. Lamins are the founding members of the family of intermediate filament
      proteins. How genes encoding cytoplasmic IF proteins could have arisen from the
      archetypal lamin gene progenitor, can be inferred from a comparison of the
      respective gene structures. The lamin/IF protein family seems to be restricted to
      the metazoans. In general, invertebrate genomes harbor only a single lamin gene
      encoding a B-type lamin. The archetypal lamin gene structure found in basal
      metazoans is conserved up to the vertebrate lineage. The completely different
      structure of lamin genes in Caenorhabditis and Drosophila are exceptions rather
      than the rule within their systematic groups. However, variation in the length of
      the coiled-coil forming central domain might be more common than previously
      anticipated. The increase in the number of lamin genes in vertebrates can be
      explained by two rounds of genome duplication. The origin of lamin A by exon
      shuffling might explain the processing of prelamin A to the mature non
      isoprenylated form of lamin A. By alternative splicing the number of vertebrate
      lamin proteins has increased even further. Lamin C, an alternative splice form of
      the LMNA gene, is restricted to mammals. Amphibians and mammals express germline
      specific lamins that differ in their protein structure from that of somatic
      lamins. Evidence is provided that there exist lamin-like proteins outside the
      metazoan lineage.

PMID- 22156748
TI  - The inner nuclear membrane proteins Man1 and Ima1 link to two different types of
      chromatin at the nuclear periphery in S. pombe.
AB  - Metazoan chromatin at the nuclear periphery is generally characterized by lowly
      expressed genes and repressive chromatin marks and presents a sub-compartment
      with properties distinct from the nuclear interior. To test whether the S. pombe
      nuclear periphery behaves similarly, we used DNA adenine methyltransferase
      identification (DamID) to map the target loci of two inner nuclear membrane
      proteins, Ima1 and Man1. We found that peripheral chromatin shows low levels of
      RNA-Polymerase II and nucleosome occupancy, both characteristic of repressed
      chromatin regions. Consistently, lowly expressed genes preferentially associate
      with the periphery and highly expressed genes are depleted from it. When looking
      at peripheral intergenic regions (IGRs), we found that divergent IGRs are
      enriched compared with convergent IGRs, indicating that transcription
      preferentially points away from the periphery rather than toward it.
      Interestingly, we found that Ima1 and Man1 have common, but also separate target
      regions in the genome. Ima1-interacting loci were enriched for the RNAi
      components Dcr1 and Rdp1. This agrees with previous findings that Dcr1 is
      localized at the nuclear periphery. In contrast, Man1 target loci were bound by
      the heterochromatin protein Swi6, especially at subtelomeric regions.
      Subtelomeric chromatin was shown to form a unique chromatin type lacking both
      repressive and active chromatin features and containing low levels of the histone
      variant H2A.Z. Thus, we find that the fission yeast nuclear periphery shows
      similar properties to those of metazoan cells, despite the absence of a nuclear
      lamina. Our results point to a role of nuclear membrane proteins in organizing
      chromatin domains and loops.

PMID- 22156750
TI  - Paracetamol prescription by age or by weight?

PMID- 22156751
TI  - Association of AKI with adverse outcomes in burned military casualties.
AB  - BACKGROUND AND OBJECTIVES: Although associated with increased morbidity and
      mortality, AKI has not been systematically examined in military personnel injured
      from combat operations in Iraq and Afghanistan. DESIGN, SETTINGS, PARTICIPANTS, &
      MEASUREMENTS: Patients evacuated from Iraq and Afghanistan to a burn unit were
      examined. AKI was classified by the Acute Kidney Injury Network (AKIN) and Risk
      Injury-Failure-Loss-End Stage (RIFLE) schemas. Age, sex, percentage of total body
      surface area burned (TBSA), percentage of full-thickness burn, inhalation injury,
      and injury severity score were recorded. Additional data that could be associated
      with poor outcomes were recorded for patients with TBSA >=20%. Multivariate
      logistic regression analyses were performed to determine factors associated with
      morbidity and mortality. RESULTS: AKI prevalence rates by the RIFLE and AKIN
      criteria were 23.8% and 29.9%, respectively. After logistic regression, RIFLE
      categories of risk (odds ratio [OR], 15.34; 95% confidence interval [CI], 1.75
      134; P=0.01), injury (OR, 46.28; 95% CI, 5.02-427; P<0.001), and failure (OR,
      126; 95% CI, 13.39->999; P<0.001); AKIN-2 (OR, 23.70; 95% CI, 2.32-242; P=0.008);
      and AKIN-3 (OR, 130; 95% CI, 13.38->999; P<0.001) were significantly associated
      with death. AKIN-3, injury, and failure remained significant in the subset of
      patients with >=20% TBSA. There was also a strong interaction between TBSA and
      the stage of AKI with respect to ventilator and intensive care unit days.
      CONCLUSIONS: AKI is prevalent in military casualties with burn injury and is
      independently associated with morbidity and mortality after adjustment for
      factors associated with injury severity.

PMID- 22156752
TI  - The risk for medial arterial calcification in CKD.
AB  - BACKGROUND AND OBJECTIVES: CKD is a risk factor for medial artery calcification,
      but the CKD stage at which this risk begins is unknown. Because breast arterial
      calcification (BAC) is a marker of generalized medial arterial calcification,
      mammography was used to detect medial arterial calcification in women with
      different CKD stages. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a
      retrospective, cross-sectional study of women with and without CKD matched for
      age and diabetes and identified from mammograms obtained in 2006-2011. BAC was
      scored as present or absent per visual inspection. RESULTS: A total of 146 women
      with stage 3 CKD and 54 with stage 4/5 CKD were identified. An additional 21
      patients with ESRD were identified and added to a previous cohort of 71 patients.
      Mean age was 64 years for CKD 3, 63 for CKD 4, and 59 for ESRD. Half of each
      group had diabetes. Compared with controls, the odds ratios for BAC were 1.44 in
      CKD 3 (95% confidence interval [CI], 0.82-2.53), 2.69 in CKD 4 (95% CI, 1.14
      6.33), and 7.19 in ESRD (95% CI, 3.77-13.7) and did not differ with diabetic
      status or race. In a multivariable logistic model, age (P<0.001) and estimated
      GFR (P=0.005) were independent predictors of BAC. The odds ratio for BAC
      increased 4% for each milliliter per minute per 1.73 m(2) decrease in estimated
      GFR. The prevalence of BAC in CKD was increased in each decade of age over 49
      years. CONCLUSIONS: CKD is an independent risk factor for medial arterial
      calcification.

PMID- 22156753
TI  - Dialysis modality and outcomes in kidney transplant recipients.
AB  - BACKGROUND AND OBJECTIVES: The influence of pretransplant dialysis modality on
      post-transplant outcomes is not clear. This study examined associations of
      pretransplant dialysis modality with post-transplant outcomes in a large national
      cohort of kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Linking the 5-year patient data of a large dialysis organization to
      the Scientific Registry of Transplant Recipients, 12,416 hemodialysis and 2092
      peritoneal dialysis patients who underwent first kidney transplantation were
      identified. Mortality or graft failure and delayed graft function risks were
      estimated by Cox regression (hazard ratio) and logistic regression (odds ratio),
      respectively. RESULTS: Recipients treated with peritoneal dialysis
      pretransplantation had lower (21.9/1000 patient-years [95% confidence interval:
      18.1-26.5]) crude all-cause mortality rate than those recipients treated with
      hemodialysis (32.8/1000 patient-years [30.8-35.0]). Pretransplant peritoneal
      dialysis use was associated with 43% lower adjusted all-cause and 66% lower
      cardiovascular death. Furthermore, pretransplant peritoneal dialysis use was
      associated with 17% and 36% lower unadjusted death-censored graft failure and
      delayed graft function risk, respectively. However, after additional adjustment
      for relevant covariates, pretransplant peritoneal dialysis modality was not a
      significant predictor of death-censored graft failure delayed graft function,
      respectively. Similar trends were noted on analyses using a propensity score
      matched cohort of 2092 pairs of patients. CONCLUSIONS: Compared with
      hemodialysis, patients treated with peritoneal dialysis before transplantation
      had lower mortality but similar graft loss or delayed graft function. Confounding
      by residual selection bias cannot be ruled out.

PMID- 22156754
TI  - Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from
      a single institution.
AB  - BACKGROUND AND OBJECTIVES: To better define the clinical-pathologic spectrum and
      prognosis of monoclonal immunoglobulin deposition disease (MIDD), this study
      reports the largest series. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Characteristics of 64 MIDD patients who were seen at Mayo Clinic are provided.
      RESULTS: Of 64 patients with MIDD, 51 had light chain deposition disease, 7 had
      heavy chain deposition disease, and 6 had light and heavy chain deposition
      disease. The mean age at diagnosis was 56 years, and 23 patients (36%) were <=50
      years of age. Clinical evidence of dysproteinemia was present in 62 patients
      (97%), including multiple myeloma in 38 (59%). M-spike was detected on serum
      protein electrophoresis in 47 (73%). Serum free light chain ratio was abnormal in
      all 51 patients tested. Presentation included renal insufficiency, proteinuria,
      hematuria, and hypertension. Nodular mesangial sclerosis was seen in 39 patients
      (61%). During a median of 25 months of follow-up (range, 1-140) in 56 patients,
      32 (57%) had stable/improved renal function, 2 (4%) had worsening renal function,
      and 22 (39%) progressed to ESRD. The mean renal and patient survivals were 64 and
      90 months, respectively. The disease recurred in three of four patients who
      received a kidney transplant. CONCLUSIONS: Patients with MIDD generally present
      at a younger age than those with light chain amyloidosis or light chain cast
      nephropathy. Serum free light chain ratio is abnormal in all MIDD patients,
      whereas only three-quarters have abnormal serum protein electrophoresis. The
      prognosis for MIDD is improving compared with historical controls, likely
      reflecting earlier detection and improved therapies.

PMID- 22156755
TI  - Cerebrospinal fluid proteins predict longitudinal hippocampal degeneration in
      early-stage dementia of the Alzheimer type.
AB  - OBJECTIVE: Biomarkers are needed to improve the sensitivity and accuracy of
      diagnosis, and also prognosis, in individuals with early Alzheimer disease (AD).
      Measures of brain structure and disease-related proteins in the cerebrospinal
      fluid (CSF) have been proposed as biomarkers, yet relatively little is known
      about the relationships between such measures. The present study was conducted to
      assess the relationship between CSF Abeta and tau protein levels and longitudinal
      measures of hippocampal structure in individuals with and without very mild
      dementia of the Alzheimer type. DESIGN: A single CSF sample and longitudinal
      magnetic resonance scans were collected. The CSF samples were assayed for tau,
      phosphorylated tau181 (p-tau181), Abeta1-42, and Abeta1-40 using an enzyme-linked
      immunosorbent assay. Large-deformation diffeomorphic metric mapping was used to
      generate hippocampal surfaces, and a composite hippocampal surface (previously
      constructed from 86 healthy participants) was used as a structural reference.
      PATIENTS OR OTHER PARTICIPANTS: Thirteen participants with very mild AD (Clinical
      Dementia Rating, CDR 0.5) and 11 cognitively normal participants (CDR 0).
      INTERVENTION: None. MAIN OUTCOME MEASURES: Initial and rate-of-change measures of
      total hippocampal volume and displacement of the hippocampal surface within zones
      overlying the CA1, subiculum, and CA2-4+DG cellular subfields, and their
      correlations with initial CSF measures. RESULTS: Lower CSF Alphabeta1-42 levels
      and higher tau/Alphabeta1-42 and p-tau181/Alphabeta1-42 ratios were strongly
      correlated with decreases in hippocampal volume and measures of progressive
      inward deformations of the CA1 subfield in participants with early AD, but not in
      cognitively normal participants. CONCLUSIONS: Despite the small sample size, we
      found that Alphabeta1-42 related and tau-related CSF measures were associated
      with hippocampal degeneration in individuals with clinically diagnosed early AD
      and may reflect an association with a common underlying disease mechanism.

PMID- 22156757
TI  - Current world literature.

PMID- 22156756
TI  - Age-specific and sex-specific prevalence and incidence of mild cognitive
      impairment, dementia, and Alzheimer dementia in blacks and whites: a report from
      the Einstein Aging Study.
AB  - As the population ages, the need to characterize rates of cognitive impairment
      and dementia within demographic groups defined by age, sex, and race becomes
      increasingly important. There are limited data available on the prevalence and
      incidence of amnestic mild cognitive impairment (aMCI) and nonamnestic mild
      cognitive impairment (naMCI) from population-based studies. The Einstein Aging
      Study, a systematically recruited community-based cohort of 1944 adults aged 70
      or older (1168 dementia free at baseline; mean age, 78.8 y; average follow-up,
      3.9 y), provides the opportunity to examine the prevalence and incidence rates
      for dementia, Alzheimer dementia (AD), aMCI, and naMCI by demographic
      characteristics. Dementia prevalence was 6.5% (4.9% AD). Overall dementia
      incidence was 2.9/100 person-years (2.3/100 person-years for AD). Dementia and AD
      rates increased with age but did not differ by sex. Prevalence of aMCI was 11.6%,
      and naMCI prevalence was 9.9%. aMCI incidence was 3.8 and naMCI incidence was
      3.9/100 person-years. Rates of aMCI increased significantly with age in men and
      in blacks; sex, education, and race were not significant risk factors. In
      contrast, naMCI incidence did not increase with age; however, blacks were at
      higher risk compared with whites, even when controlling for sex and education.
      Results highlight the public health significance of preclinical cognitive
      disease.

PMID- 22156759
TI  - Femtosecond laser-assisted half-top-hat keratoplasty.
AB  - Shaped keratoplasties, such as the top-hat, zigzag, and mushroom keratoplasties,
      have been reported in the literature to have advantages over traditional
      penetrating keratoplasty. The manual versions of these techniques have not gained
      widespread use, most likely because of the difficulty of the surgical technique
      of manual dissection. Use of a femtosecond laser allows for more consistent
      results, but this device is not available in the majority of operating theaters
      worldwide. Here, I describe a modification to the manual half-top-hat technique
      described by Kaiserman et al that allows for a shaped penetrating keratoplasty
      without the use of any additional equipment in the operating theater and does not
      require any additional steps beyond those of traditional penetrating keratoplasty
      by the operating surgeon.

PMID- 22156760
TI  - Stroke prediction after transient ischemic attacks in patients admitted to a
      stroke unit.
AB  - BACKGROUND: Transient ischemic attacks (TIAs) bear a presumed high risk of early
      recurrence of stroke. Data in the literature, however, are inconsistent, as
      recurrence rates range from 9.5 to 20%, at 90 days. AIMS: The study was designed
      to determine the risk of stroke after TIA. METHODS: 94 consecutive patients
      referred to a Stroke Unit for TIA or minor stroke, within 24 h of symptom onset,
      were recruited. Eleven of the 94 patients (12%, 95% CI: 7-20%) had a relapse
      within 90 days. The relapse consisted of a TIA for 9 patients (10%, 95% CI: 5
      17%), or of a stroke for 2 subjects (1%, 95% CI: 0-8%). More than a quarter of
      the relapses occurred within 1 week from the first TIA. ABCD(2), ABCD(2)-I and
      ABCD-E+ scores were similar among people with or without relapse. CONCLUSIONS:
      The data seem to confirm previous reports on the relatively low relapse rate for
      stroke, when TIA patients are promptly assisted in dedicated structures. The
      findings stress the potential benefit of early intervention in subjects with TIA.

PMID- 22156761
TI  - A rare cause of intractable asthma.

PMID- 22156763
TI  - Association of polymorphisms in the AGT gene with essential hypertension in the
      Chinese population.
AB  - OBJECTIVE: Although the angiotensinogen (AGT) gene has been implicated in the
      pathogenesis of essential hypertension, the results have been inconsistent. In
      this study, we performed a meta-analysis to assess the association of A-6G, A-20C
      and G-217A polymorphisms in the AGT gene with essential hypertension in the
      Chinese population. METHODS: Published literature from PubMed, Embase, China
      National Knowledge Infrastructure, China Biological Medicine and Wanfang Data was
      retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was
      calculated using fixed- or random-effects models. RESULTS: Sixteen studies (4223
      cases and 3743 controls) for A-6G polymorphism, ten studies (3116 cases and 2678
      controls) for A-20C polymorphism and five studies (1268 cases and 1081 controls)
      for G-217A polymorphism were identified. The results from the meta-analyses
      indicated significant association of all three polymorphism with the risk of
      essential hypertension in the Chinese population (A-6G polymorphism: GG vs AA: OR
      = 1.45, 95% CI 1.17-1.81; A-20C polymorphism: CC vs AA: OR = 1.52, 95% CI 1.10
      2.08; G-217A polymorphism: AA vs GG: OR = 2.36, 95% CI 1.44-3.89). CONCLUSIONS:
      Our study indicated that three polymorphisms (A-6G, A-20C and G-217A) in the AGT
      gene are associated with essential hypertension in the Chinese population.

PMID- 22156762
TI  - Typhoid fever: "you can't hit what you can't see".
AB  - The host restricts dissemination of invasive enteric pathogens, such as non
      typhoidal Salmonella serovars, by mounting acute inflammatory responses
      characterized by the recruitment of neutrophils. However, some enteric pathogens,
      such as Salmonella enterica serovar Typhi (S. typhi), can bypass these defenses
      and cause an invasive bloodstream infection known as typhoid fever. Recent
      studies on virulence mechanisms of S. typhi suggest that tight regulation of
      virulence gene expression during the transition from the intestinal lumen into
      the intestinal mucosa enables this pathogen to evade detection by the innate
      immune system, thereby penetrating defenses that prevent bacterial dissemination.
      This example illustrates how the outcome of host pathogen interaction at the
      intestinal mucosal interface can alter the clinical presentation and dictate the
      disease outcome.

PMID- 22156764
TI  - Striatal dopamine transporter availability in drug-naive patients with
      schizophrenia: a case-control SPECT study with [(99m)Tc]-TRODAT-1 and a meta
      analysis.
AB  - Central dopaminergic hyperactivity has been one of the main hypotheses of the
      pathophysiology of schizophrenia since the 1970s. Excess dopamine (DA)
      neurotransmission in the striatum is hypothesized to alter the processing of
      information and result in psychotic symptoms in schizophrenia. Single photon
      emission computerized tomography (SPECT) provides in vivo indices of DA
      neurotransmission. Our study aimed to compare dopamine transporter (DAT)
      availability between drug-naive patients with schizophrenia and controls using
      SPECT. DAT availability through [(99m)Tc]-TRODAT-1 SPECT was compared between 47
      drug-naive patients with recent-onset schizophrenia and 112 healthy controls. We
      also conducted a random-effects meta-analysis of the available literature
      synthesizing the results of 6 comparable published articles as well as our
      current data. The mean specific striatal binding showed a statistical trend for a
      reduction among the patients compared with controls (estimated difference =
      0.071; 95% CI -0.01, 0.15; P = .08). There was an effect of gender, whereby
      females had a higher ratio of specific striatal binding than males. Age was
      negatively correlated with the ratio of specific striatal binding, both in
      patients and controls. The meta-analysis provided a pooled standardized effect
      size (Cohen's d) of -0.07 (95% CI -0.31, 0.18; P = .60) for the patient vs
      control comparison in TRODAT binding, with no evidence of heterogeneity between
      studies or publication bias. Our findings suggest that striatal DAT levels are
      not altered in the early stages of schizophrenia before medication is introduced.
      We identified gender differences and aging effects that could have significance
      for future studies.

PMID- 22156765
TI  - Phase I clinical trial of alternating belotecan and oral etoposide in patients
      with platinum-resistant or heavily treated ovarian cancer.
AB  - This study was designed to determine the maximum tolerated dose and toxicity
      profile of belotecan in combination with oral etoposide in patients with platinum
      resistant or heavily treated ovarian cancer, fallopian tubal cancer, and primary
      peritoneal cancer. Belotecan (0.5 mg/m/day) was administered daily (days 1-5)
      followed by etoposide (50, 75 mg/day) for up to 5 days (days 6-10) every 3 weeks.
      Dose-limiting toxicities (DLT) were defined as follows: grade 4 neutropenia less
      than 1 week; either neutropenic fever less than 24 h or sepsis; grade 4
      thrombocytopenia; and grade of at least 3 nonhematologic toxicity except
      alopecia. At the first dose level (50 mg) of etoposide, none of the three
      patients developed DLT, whereas DLT was observed in two of three patients at the
      next dose level. Thus, the dose level was reduced to 50 mg, and another three
      patients were enrolled. DLT was found in one of six patients who received
      etoposide at the dose level of 50 mg/m. Thus, the maximum tolerated dose was
      reached (50 mg of oral etoposide) and the trial was terminated. The response was
      evaluable in nine patients and an objective response was observed in four
      patients (44%) including two complete responses. The combined regimen of
      belotecan followed by oral etoposide showed promising activity in platinum
      resistant or heavily pretreated ovarian cancer patients at the dose level of 50
      mg of oral etoposide.

PMID- 22156766
TI  - Spontaneous eyeblink rate in focal cerebrovascular lesions.
AB  - BACKGROUND: The involvement of different brain areas in spontaneous eyeblink rate
      control is largely unknown. METHODS: Spontaneous eyeblink rate was assessed in
      211 consecutive acute stroke patients within two days after symptom onset and was
      correlated with infarction location as well as with other parameters such as the
      presence of hemineglect or significant small vessel disease in MRI or CT scans.
      Blink rates were measured in two conditions: (1) during a trivial conversation
      requiring no cognitive effort and (2) during mental arithmetic. RESULTS: Patients
      and healthy controls displayed similar average blink rates at rest (19.1 and 17.3
      blinks/min, respectively) and during mental arithmetic (22.6 and 20.2 blinks/min,
      respectively). The latter condition reliably increased blinking frequency in both
      patients and control subjects. The subgroups of patients with frontal,
      frontoparietal and frontotemporal infarctions exhibited a significantly higher
      blink rate modulation, expressed as an increased relative difference of blinking
      at rest compared with blinking during mental arithmetic. CONCLUSION: As a whole,
      patients with acute cerebrovascular disease do not show changes in blink rate.
      Subjects with frontal infarcts, however, systematically increase their blink
      rates during cognitive effort, most probably due to a lack of frontal inhibitory
      control on blinking modulation.

PMID- 22156767
TI  - The helpful or hindering effects of in-hospital patient monitor alarms on nurses:
      a qualitative analysis.
AB  - Patient monitors generate alarms to signal changes in vital signs. Some research
      suggests these alarms can improve patient safety. Other reports caution that
      these systems generate false alarms and create nursing workflow interruptions.
      These findings require contextualization by qualitatively investigating the lived
      experiences of nurses working with these monitors. Research into the dynamics
      involved in nursing responses to alarms can provide insights for monitor
      development and implementation. This study's purposes were (1) to describe the
      frequency of alarms generated by patient monitors and nursing responses and (2)
      to report nurses' explanations of the impact of alarms on workflow and strategies
      for responding to alarms. Forty-nine hours of observations and 14 interviews were
      conducted at a Canadian medical center. Four hundred forty-six monitor alarms (1
      every 6.59 minutes) were observed. Of these, 70% had no immediate response from
      nurses. Furthermore, 34 red alarms (potential life-threatening) were observed,
      with 41% having no immediate response. Nurses reported feeling overloaded by
      alarm frequency. They described learning to interpret alarm data and developing
      workaround strategies (eg, ignoring alarms). Paradoxically, alarms prompted
      nurses to regularly consider and interpret patient information. We suggest the
      interpretive work associated with workarounds may hold benefits mitigating the
      potential harms of ignoring alarms.

PMID- 22156768
TI  - An investigation on task-technology fit of mobile nursing information systems for
      nursing performance.
AB  - This study investigates factors affecting the fit between nursing tasks and
      mobile nursing information systems and the relationships between the task
      technology fit of mobile nursing information systems and nurse performance from
      the perspective of task-technology fit. Survey research recruited nursing staffs
      as subjects from selected case hospital. A total of 310 questionnaires were sent
      out, and 219 copies were obtained, indicating a valid response rate of 70.6%.
      Collected data were analyzed using the structural equation modeling technique.
      Our study found that dependence tasks have positive effects on information
      acquisition (gamma=0.234, P<.05) and information identification (gamma=0.478,
      P<.001), and independent tasks have significant effects on information
      acquisition (gamma=0.213, P<.05). Therefore, the introduction of mobile nursing
      information systems in assisting nursing practices can help facilitate both
      independent and dependent nursing tasks. Our study discovered that the supporting
      functions of mobile nursing information systems have positive effects on
      information integration and interpretation (gamma=0.365, P<.001), as well as
      information acquisition (gamma=0.253, P<.05). The service supports of mobile
      nursing information systems have positive effects on information acquisition
      (gamma=0.318, P<.001) and information integration and interpretation
      (gamma=0.143, P<.01). Furthermore, information identification (beta=.055, P<.05),
      information acquisition (beta=.176, P<.001), and information integration and
      interpretation (beta=.706, P<.001) provided using mobile nursing information
      systems have positive effects on nursing performance, indicating 83.2% of totally
      explained variance. As shown, the use of mobile nursing information systems could
      provide nursing staffs with real-time and accurate information to increase
      efficiency and effectiveness in patient-care duties, further improving nursing
      performance.

PMID- 22156769
TI  - Updating and normalization of the Nursing Management Minimum Data Set element 6:
      patient/client accessibility.
AB  - Patient/client accessibility is one of 18 Nursing Management Minimum Data Set
      data elements developed to evaluate contextual factors at the nursing unit or
      service level of care. The Nursing Management Minimum Data Set 06 patient/client
      accessibility was developed to capture variability in time and distance required
      to access patients. Variability in access to patients, needed supplies,
      equipment, and information for patient care has an impact on the amount of time
      available for direct patient care. Limitations in time available to provide safe
      and quality care may negatively affect patient outcomes, nurse retention, and, as
      a result, a healthcare organization's accreditation and finances. Since 2005, the
      first five Nursing Management Minimum Data Set data elements have been
      incorporated into the publicly accessible healthcare data set Logical Observation
      Identifier Names and Codes, thereby making results derived from these nursing
      management data elements available for empirical use. A critical review of the
      literature and other healthcare resources was conducted to update patient/client
      accessibility. A consensus approach was used by an interdisciplinary panel of
      experts to finalize recommendations for revisions. The name, conceptual and
      operational definitions, and measures were updated. The revised data element is
      titled "client accessibility." The conceptual and operational definitions were
      expanded and measures changed to increase validity and reliability of data
      collection. The updated conceptual definition is "the time, distance, and method
      to connect the nurse/provider and client for an encounter and includes the
      information, supplies, equipment, and personnel required for the encounter." The
      Nursing Management Minimum Data Set can provide individuals responsible for
      managing and financing nursing resources with quantifiable data regarding the
      context of nursing care. At present, healthcare costs are rising at an
      unsustainable rate, and many national healthcare outcomes are worsening. More
      information is needed to identify potential areas of improvement in the
      management and funding of nursing care. The update and use of Nursing Management
      Minimum Data Set 06 data element client accessibility may help to identify
      problem areas associated with nursing time, distance traveled, and methods used
      to provide patient care. Such empirical evidence may support better informed
      decisions on caseloads in diverse settings, hospital designs, methods used to
      provide care, and fiscal requirements.

PMID- 22156770
TI  - ES cell differentiation system recapitulates the establishment of imprinted gene
      expression in a cell-type-specific manner.
AB  - Genomic imprinting is a phenomenon whereby monoallelic gene expression occurs in
      a parent-of-origin-specific manner. A subset of imprinted genes acquires a tissue
      specific imprinted status during the course of tissue development, and this
      process can be analyzed by means of an in vitro differentiation system utilizing
      embryonic stem (ES) cells. In neurons, the gene Ube3a is expressed from the
      maternal allele only, and a paternally expressed non-coding, antisense RNA has
      been implicated in the imprinting process in mice and humans. Here, to study the
      genomic imprinting mechanism, we established F1 hybrid ES cells derived from two
      sub-species of Mus musculus and established an in vitro neuronal differentiation
      system in which neuron-specific imprinting of Ube3a was recapitulated. With this
      system, we revealed that the switch from biallelic expression to maternal,
      monoallelic expression of Ube3a occurs late in neuronal development, during the
      neurite outgrowth period, and that the expression of endogenous antisense
      transcript from the Ube3a locus is up-regulated several hundred-fold during the
      same period. Our results suggest that evaluation of the quality of ES cells by
      studying their differentiation in vitro should include evaluation of epigenetic
      aspects, such as a comparison with the genomic imprinting status found in tissues
      in vivo, in addition to the evaluation of differentiation gene markers and
      morphology. Our F1 hybrid ES cells and in vitro differentiation system will allow
      researchers to investigate complex end-points such as neuron-specific genomic
      imprinting, and our F1 hybrid ES cells are a useful resource for other tissue
      specific genomic imprinting and epigenetic analyses.

PMID- 22156771
TI  - Detailed metabolic and genetic characterization reveals new associations for 30
      known lipid loci.
AB  - Almost 100 genetic loci are known to affect serum cholesterol and triglyceride
      levels. For many of these loci, the biological function and causal variants
      remain unknown. We performed an association analysis of the reported 95 lipid
      loci against 216 metabolite measures, including 95 measurements on lipids and
      lipoprotein subclasses, obtained via serum nuclear magnetic resonance
      metabolomics and four enzymatic lipid traits in 8330 individuals from Finland.
      The genetic variation in the loci was investigated using a dense set of 440 807
      directly genotyped and imputed variants around the previously identified lead
      single nucleotide polymorphisms (SNPs). For 30 of the 95 loci, we identified new
      metabolic or genetic associations (P < 5 * 10(-8)). In the majority of the loci,
      the strongest association was to a more specific metabolite measure than the
      enzymatic lipids. In four loci, the smallest high-density lipoprotein measures
      showed effects opposite to the larger ones, and 14 loci had associations beyond
      the individual lipoprotein measures. In 27 loci, we identified SNPs with a
      stronger association than the previously reported markers and 12 loci harboured
      multiple, statistically independent variants. Our data show considerable
      diversity in association patterns between the loci originally identified through
      associations with enzymatic lipid measures and reveal association profiles of far
      greater detail than from routine clinical lipid measures. Additionally, a dense
      marker set and a homogeneous population allow for detailed characterization of
      the genetic association signals to a resolution exceeding that achieved so far.
      Further understanding of the rich variability in genetic effects on metabolites
      provides insights into the biological processes modifying lipid levels.

PMID- 22156774
TI  - Antiretroviral therapy for naive and for treatment-experienced HIV patients, and
      prevention of HIV transmission.

PMID- 22156775
TI  - Virologic suppression in treatment-experienced patients after virologic rebound
      or failure of therapy.
AB  - PURPOSE OF REVIEW: To discuss factors related to virologic failure and review
      data from recent clinical trials evaluating re-suppression of viremia in
      extensively-treated HIV-infected patients with resistance. RECENT FINDINGS:
      Factors associated with virologic failure can be related to the virus (e.g.
      resistance), the patient (e.g. adherence) or HIV therapy (e.g. availability) and
      must be analyzed to minimize the likelihood of a new failure. Recent clinical
      trials have shown that it is now possible to achieve virologic suppression in a
      large proportion of treatment-experienced patients with extensive drug
      resistance, with several newer agents demonstrating favorable potency,
      tolerability and long-term efficacy. SUMMARY: The benefits of highly active
      antiretroviral treatment are well recognized, and adding at least two (preferably
      three) new active drugs to an optimized background regimen can provide effective
      suppression of viremia even in multidrug-experienced patients. Changing drugs or
      regimen simplification should be considered when treatment is inadequate, poorly
      tolerated or associated with poor adherence, and is made easier by the newer
      agents and formulations now available. Newer antiretrovirals may contribute to a
      better quality of life and life expectancy in patients with few or no therapy
      options, although adherence is paramount in ensuring their continued
      effectiveness.

PMID- 22156776
TI  - Recent advances in antiretroviral treatment and prevention in HIV-infected
      patients.
AB  - PURPOSE OF REVIEW: To discuss new antiretroviral agents (ARVs) and alternative
      ARV treatment strategies that are currently being evaluated, and to provide an
      overview of the most recent advances in HIV vaccine development. RECENT FINDINGS:
      There is a continuous need for improvements in ARV therapy (ART) and several new
      ARVs are currently undergoing clinical investigation, including the non
      nucleoside reverse transcriptase inhibitor rilpivirine, the integrase inhibitor
      elvitegravir, the chemokine receptor 5 co-receptor antagonist vicriviroc and the
      maturation inhibitor bevirimat. Strategies to optimize ART, such as treatment
      interruption, induction-maintenance and class-sparing regimens, are also being
      evaluated and have had varying success to date. However, vaccination still
      remains the optimal solution, and one second-generation preventative HIV vaccine
      has produced encouraging results in a recent phase III trial. SUMMARY: Global
      prevention and treatment with ARVs that are effective, well tolerated and have
      high barriers to the development of HIV resistance are the main strategies to
      fight HIV/AIDS while we await the development of an effective vaccine.

PMID- 22156777
TI  - Antiretroviral therapy in treatment-naive patients with HIV infection.
AB  - PURPOSE OF REVIEW: This review discusses the current status of antiretroviral
      therapy (ART) in treatment-naive patients. ART initiation in such patients needs
      to be carefully planned, as the aim of therapy has shifted from prolonging life
      to ensuring maintained adherence to ART and optimization of quality of life.
      There is a plethora of first-line antiretroviral agents available, and physicians
      must consider several patient-related and therapy-related factors before
      selecting the most appropriate initial ART. RECENT FINDINGS: Current treatment
      guidelines recommend the use of nonnucleoside reverse transcriptase inhibitor
      (NNRTI), ritonavir-boosted protease inhibitor (PI), or integrase strand transfer
      inhibitor (INSTI)-based regimens in treatment-naive patients. Treatment selection
      and modification to achieve optimal response is based primarily on regular
      assessment of viral load (and resistance testing if necessary) and CD4 cell
      count. The use of genotypic resistance testing, on initiation of therapy and on
      treatment failure, is becoming more widespread. In selected patients, due to
      increasing transmitted drug resistance (TDR), a PI-based regimen may be a better
      option. Classic ART combinations are being challenged by new combinations,
      although there is currently insufficient evidence to recommend use of the newer
      over classic combinations. Co-formulations of drugs and single-tablet regimens
      are fast becoming available and their convenience may increase patient treatment
      adherence. SUMMARY: All drug classes currently available for first-line ART are
      efficacious and have good tolerability; however, differences between individual
      drugs must be carefully considered when deciding a first-line regimen. Each first
      line regimen must be tailored to the individual patient to attain optimal
      efficacy, acceptable long-term tolerability, and good adherence to ART.

PMID- 22156778
TI  - Hot off the breath: triple therapy for idiopathic pulmonary fibrosis--hear the
      PANTHER roar.

PMID- 22156779
TI  - Glucocorticoid receptor beta and histone deacetylase 1 and 2 expression in the
      airways of severe asthma.
AB  - RATIONALE: Upregulation of glucocorticoid receptor beta (GRbeta) has been
      implicated in steroid resistance in severe asthma, although previous studies are
      conflicting. GRbeta has been proposed as a dominant negative isoform of
      glucocorticoid receptor alpha (GRalpha) but it has also been suggested that
      GRbeta can cause steroid resistance via reduced expression of histone deacetylase
      2 (HDAC2), a key regulator of steroid responsiveness in the airway. OBJECTIVES:
      To examine GRbeta, GRalpha, HDAC1 and HDAC2 expression at transcript and protein
      levels in bronchial biopsies from a large series of patients with severe asthma,
      and to compare the findings with those of patients with mild to moderate asthma
      and healthy volunteers. METHODS: Bronchoscopic study in two UK centres with real
      time PCR and immunohistochemistry performed on biopsies, western blotting of
      bronchial epithelial cells and immunoprecipitation with anti-GRbeta antibody.
      MEASUREMENTS AND MAIN RESULTS: Protein and mRNA expression for GRalpha and HDAC2
      did not differ between groups. GRbeta mRNA was detected in only 13 of 73 samples
      (seven patients with severe asthma), however immunohistochemistry showed
      widespread epithelial staining in all groups. Western blotting of bronchial
      epithelial cells with GRbeta antibody detected an additional 'cross-reacting'
      protein, identified as clathrin. HDAC1 expression was increased in patients with
      severe asthma compared with healthy volunteers. CONCLUSIONS: GRbeta mRNA is
      expressed at low levels in a minority of patients with severe asthma. HDAC1 and
      HDAC2 expression was not downregulated in severe asthma. These data do not
      support upregulated GRbeta and resultant reduced HDAC expression as the principal
      mechanism of steroid resistance in severe asthma. Conflicting GRbeta literature
      may be explained in part by clathrin cross-reactivity with commercial antibodies.

PMID- 22156780
TI  - Thorax in focus: chronic obstructive pulmonary disease.
AB  - Keeping up to date with scientific developments in any field of medicine is
      challenging, and chronic obstructive pulmonary disease (COPD) is no exception.
      Thorax has played an important part in the communication of key developments to
      its readership. In this article we review original research published in the
      journal over the last 2-3 years. We consider scientific and clinical developments
      in the epidemiology, mechanisms and treatment of COPD, placing these articles in
      the context of other relevant literature in COPD.

PMID- 22156781
TI  - Childhood chronic inflammatory demyelinating polyneuropathy associated with
      acquired scoliosis: a case report.
AB  - An 11-year-old boy presented with progressive proximal muscle weakness and
      areflexia. He also had scoliosis with right convexity in the thoracic spine.
      Nerve conduction studies showed demyelination with conduction blocks. The level
      of protein in the cerebrospinal fluid was elevated. Magnetic resonance imaging of
      the lumbosacral spine showed enhancement and hypertrophy of the nerve roots. The
      patient responded well to steroids. The association of acquired scoliosis with
      chronic inflammatory demyelinating polyneuropathy has not been reported before.

PMID- 22156782
TI  - A child with night blindness: preventing serious symptoms of Refsum disease.
AB  - Refsum disease is a genetic progressive neurological disorder caused by
      neurotoxic phytanic acid, a nutritional component patients are unable to
      metabolize. Symptoms include retinopathy, polyneuropathy, ataxia, and deafness.
      They are variable and rarely recognized before adulthood. The authors report the
      case of a 14-year-old girl diagnosed because of night blindness. They treated her
      with a phytanic acid-poor diet and extracorporeal lipid apheresis. They used
      different methods over a 30-month period. Thereafter, the patient was treated
      with diet only. Membrane filtration and heparin-induced extracorporeal low
      density lipoprotein precipitation apheresis were well tolerated. Withdrawal of
      phytanic acid was studied quantitatively. During a 5-year period, blood phytanic
      acid levels decreased to a noncritical range. The patient remained free of
      ophthalmological and neurological progression for a total observation of 12
      years. Early diagnosis and effective measures to keep the phytanic acid load low
      can probably prevent the serious sequelae of Refsum disease. Developing a method
      for newborn screening is desirable.

PMID- 22156783
TI  - Use of complementary and alternative medicine by males with Duchenne or Becker
      muscular dystrophy.
AB  - Use of complementary and alternative medicine by males with Duchenne or Becker
      muscular dystrophy was examined using interview reports from caregivers enrolled
      in the population-based Muscular Dystrophy Surveillance, Tracking, and Research
      Network. Of the 200 caregivers interviewed, 160 (80%) reported "ever" using
      complementary and alternative medicine for their affected children. Mind-body
      medicine (61.5%) was most frequently used, followed by biologically based
      practices (48.0%), manipulative and body-based practices (29.0%), and whole
      medical systems (8.5%). Caregivers reporting use of whole medical systems had
      higher education and income levels compared with nonusers; affected males had
      shorter disease duration. Caregivers reporting use of mind-body medicine,
      excluding aquatherapy, had higher education level compared with nonusers.
      Overall, complementary and alternative medicine use was high; disease duration,
      education, and income levels influenced use. These findings have implications for
      developing clinical care protocols and monitoring possible interactions between
      complementary and alternative medicine and conventional medical therapies.

PMID- 22156784
TI  - Catastrophic demyelinating encephalomyelitis after intrathecal and intravenous
      stem cell transplantation in a patient with multiple sclerosis.
AB  - Stem cell transplantation is an investigational therapy for multiple sclerosis.
      The authors describe a case of catastrophic demyelinating encephalomyelitis
      following stem cell transplantation in a 17-year-old girl. Nine months after an
      initial diagnosis of multiple sclerosis, she underwent stem cell transplantation
      in Costa Rica. Subsequently, she deteriorated and was transported back to the
      United States with headache and vomiting progressing to quadriparesis, locked-in
      syndrome, and superimposed encephalopathy. Magnetic resonance imaging and brain
      biopsy were consistent with fulminant demyelinating encephalomyelitis with
      enhancing parenchyma and leptomeninges. Cerebrospinal fluid analysis revealed
      lymphocytic pleocytosis and high protein. The protracted illness required
      tracheostomy and gastrostomy. After methyleprednisone, intravenous
      immunoglobulin, and cyclophosphamide, she improved during 2.5 months to an
      ambulatory, functionally independent state. Subsequently, typical less severe
      multiple sclerosis relapses occurred. This case demonstrates that stem cell
      transplantation may provoke life-threatening encephalomyelitis in patients with
      multiple sclerosis. This highlights the need to restrict transplantation to
      trials with appropriate safety controls.

PMID- 22156785
TI  - Glucose transporter type I deficiency causing mitochondrial dysfunction.
AB  - Mitochondrial disorders are varied in their clinical presentation and
      pathogenesis. Diagnosis is usually made clinically and genetic defects are often
      not identified. We present a 6-year-old female patient with a diagnosis of a
      mitochondrial disorder secondary to complex I deficiency with seizures and
      developmental delay from infancy. Glucose transporter deficiency was suspected
      after a lumbar puncture showed hypoglycorrhachia. Her disorder was confirmed
      genetically as a mutation in her solute carrier family 2, facilitated glucose
      transporter member 1 (SLCA2) gene. Delayed diagnosis led to delayed treatment,
      and neurologic sequelae may have been prevented by earlier recognition of this
      disorder.

PMID- 22156786
TI  - Continuous infusion pentobarbital for refractory status epilepticus in children.
AB  - The purpose of this retrospective medical chart review was to describe dosing
      regimens and outcomes in children who received continuous pentobarbital therapy
      for refractory status epilepticus. Thirty patients (age = 6.5 +/- 5.1 years; 67%
      male) received a mean loading dose of 5.4 +/- 2.8 mg/kg with an initial infusion
      of 1.1 +/- 0.4 mg/kg/h. Maximum infusion dose was 4.8 +/- 2 mg/kg/h. Thirty-three
      percent of patients achieved sustained burst suppression without relapse; 66.7%
      experienced relapse, but 60% of those (n = 12) eventually reachieved burst
      suppression. Children achieving burst suppression within 24 hours of
      pentobarbital initiation and those older than age 5 years were 1.5 times more
      likely to have a positive outcome. None of these variables, however, achieved
      significance (Fisher exact test). Ninety-three percent of patients required
      inotropes; 66% acquired an infection; 10% had metabolic acidosis; and 10%
      experienced pancreatitis. Poor outcomes (death, encephalopathy) were observed in
      33% of patients.

PMID- 22156787
TI  - Spinal muscular atrophy type III: trying to understand subtle functional change
      over time--a case report.
AB  - Spinal muscular atrophy is a relatively stable chronic disease. Patients may
      gradually experience declines in muscle strength and motor function over time.
      However, functional progression is difficult to document, and the mechanism
      remains poorly understood. An 11-year-old girl was diagnosed at 19 months and
      took a few steps without assistance at 25 months. She was evaluated for 54 months
      in a prospective multicenter natural history study. Outcome measures were
      performed serially. From 6 to 7.5 years, motor function improved. From 7.5 to 11
      years, motor function declined with increasing growth. Manual muscle testing
      scores minimally decreased. Motor unit number estimation studies gradually
      increased over 4.5 years. Compared to the published natural history of spinal
      muscular atrophy type III, our patient lost motor function over time. However,
      she walked with assistance 2 years longer than expected. Our report highlights
      possible precipitating factors that could affect the natural history of spinal
      muscular atrophy type III.

PMID- 22156788
TI  - Training the next generation of child neurologists: a child health-based
      approach.
AB  - In the United States, child neurologists continue to value close, historical ties
      to adult neurology. However, the mandatory year of adult training for American
      Board of Psychiatry and Neurology certification in "Neurology with Special
      Qualification in Child Neurology" deprives residents of educational opportunities
      that would yield greater benefit for children afflicted with neurologic diseases.
      The need for modernization has been recognized in a Professors of Child Neurology
      survey in which a majority of program directors favored reducing adult neurology
      training and changing the certification to "Child Neurology." This article
      reviews the rationale for an overdue transformation of Child Neurology training.

PMID- 22156789
TI  - Propionic acidemia associated with visual hallucinations.
AB  - Propionic acidemia, an autosomal recessive disorder, is a common form of organic
      aciduria resulting from the deficiency of propionyl-CoA carboxylase. It is
      characterized by frequent and potentially lethal episodes of metabolic acidosis
      often accompanied by hyperammonemia. A wide range of brain abnormalities have
      been reported in propionic acidemia. We report recurrent visual hallucinations in
      2 children with propionic acidemia. Four visual hallucination events were
      observed in the 2 patients. Three episodes were preceded by an intercurrent
      illness, and 2 were associated with mild metabolic decompensation. The 2 events
      in one patient were associated with a seizure disorder with abnormal
      electroencephalogram. Brain magnetic resonance imaging showed abnormal basal
      ganglia and faint temporo-occipital swelling bilaterally. This is probably the
      first report of visual hallucinations in propionic acidemia and should alert the
      treating clinicians to look for visual hallucinations in patients with organic
      acidurias, especially in an unusually anxious child.

PMID- 22156790
TI  - Secondary erythromelalgia successfully treated with intravenous immunoglobulin.
AB  - Erythromelalgia is a rare condition characterized by episodic painful erythema
      and warmth often affecting, but not limited to, the distal extremities. This
      condition is notoriously difficult to treat. We report a young female patient
      with seronegative polyarthritis who presented with a 6-year history of recurrent
      bouts of painful erythema and swelling often triggered by minor trauma. An
      extensive evaluation was unremarkable. Several medical therapies provided limited
      and inconsistent relief of her symptoms over many years. Treatment with
      intravenous immunoglobulin significantly decreased the frequency and severity of
      her symptoms.

PMID- 22156791
TI  - Child neurology residency: system implications of new training models.
AB  - From limitations on residents' duty hours, to ways in which outcomes are
      measured, changes to graduate medical education are sweeping the nation. In this
      issue of the journal, Gilbert and Greenwood present thoughtful, if somewhat
      disparate, opinions on ways to improve the educational experience of child
      neurology trainees. As the Designated Institutional Officer of a large children's
      hospital, I have focused my commentary on "the big picture." That is, what
      systemwide impact can changes in child neurology trainees' education have.

PMID- 22156792
TI  - Further magnetic resonance imaging (MRI) brain delineation of 49,XXXXY syndrome.
AB  - A rare sex chromosome aneuploidy syndrome, 49,XXXXY syndrome is characterized by
      mental retardation with severe learning difficulties, craniofacial and skeletal
      abnormalities, hypogonadism, and congenital heart disease. The authors describe a
      30-month-old boy with 49,XXXXY syndrome, global developmental delay and white
      matter changes in the brain magnetic resonance imaging. They reviewed the
      literature to delineate a specific magnetic resonance imaging pattern of 49,XXXXY
      syndrome.

PMID- 22156793
TI  - Future directions in palliative thoracic radiotherapy.
AB  - PURPOSE OF REVIEW: Recent systematic review, practice guidelines, and consensus
      statements have summarized the known clinical trial information with regards to
      the appropriate use of external-beam radiation, brachytherapy, and concurrent
      chemotherapy (with external-beam radiotherapy) in the palliation of chest
      symptoms with thoracic radiotherapy. The purpose of this review is to describe
      our present knowledge with regards to palliative thoracic radiotherapeutic
      maneuvers and to identify potential areas for future research inquiry consistent
      with current knowledge gaps. RECENT FINDINGS: Two systematic reviews, one
      practice guideline, and one consensus statement based on published prospective
      clinical trials have demonstrated that palliative thoracic radiotherapy is an
      effective modality both in terms of symptom palliation and other important cancer
      outcomes. Evolving areas for future scientific inquiry include the role of
      advanced technologies such as intensity-modulated radiation therapy and image
      guided radiation therapy, economic analyses as well as the creation of a common
      palliative endpoint that can be used for future clinical trials. SUMMARY: Robust
      clinical trial information and high-level knowledge-translation documents
      currently exist to guide radiotherapy practitioners to provide standard-of-care
      treatment for thoracic palliative scenarios.

PMID- 22156794
TI  - Malignant epidural spinal cord compression:  the role of external beam
      radiotherapy.
AB  - PURPOSE OF REVIEW: Spinal cord compression is a common complication of metastatic
      malignancy. If not diagnosed and treated early when the patient is still able to
      ambulate, outcomes and survival are poor. The purpose of this study is to review
      treatment options for patients presenting with metastatic spinal cord compression
      and emphasize the importance of early diagnosis. This review also aims to
      highlight the need for ongoing research to improve patient outcomes. RECENT
      FINDINGS: Recent literature suggests that treatment choices should take into
      account overall patient prognosis and ambulation status at diagnosis. In
      particular, poor prognosis patients can be treated with short courses of
      radiation and longer courses of radiation may be associated with better local
      control and therefore should be considered for good prognosis patients. Patient
      prognosis can be estimated using validated scoring systems. MRI screening may be
      of benefit in selected patient groups deemed at high risk of developing spinal
      cord compression. SUMMARY: Despite being a common complication of metastatic bone
      disease, there is a paucity of high-level evidence to guide treatment practice.
      Current and future randomized trials are vital.

PMID- 22156795
TI  - Sorafenib, but not sunitinib, induces regulatory T cells in the peripheral blood
      of patients with metastatic renal cell carcinoma.
AB  - Induction of regulatory T cells (Treg) is an important mechanism leading to
      tolerance against tumors. Increased levels of Treg have been described in renal
      cell carcinoma (RCC) patients and seem to correlate with an adverse outcome. Our
      study aimed to analyze the influence of sorafenib and sunitinib on the frequency
      of Treg in patients with metastatic RCC (mRCC). Treg were analyzed by flow
      cytometry in the peripheral blood (PB) of patients (n=19) with histologically
      confirmed mRCC under treatment with either sunitinib (50 mg/d, n=11) or sorafenib
      (800 mg/d, n=8). Blood samples were taken before treatment and during the first,
      second, and third months of therapy. Flow cytometric analysis of PB mononuclear
      cells was performed using fluorochrome-labeled antibodies against CD3, CD4, CD25,
      and FOXp3. During the first month of therapy, patients treated with sorafenib
      showed a significant increase in FOXp3CD3CD4CD25 Treg (13.5 vs. 36.3% of gated
      cells, P=0.02, or 0.35 vs. 0.49% of total cells) and the ratio FOXp3 T
      cells/FOXp3 T cells (0.16 vs. 0.56 of gated cells, P=0.02). These elevated levels
      persisted throughout the treatment period. There was no influence of sunitinib on
      the frequency of Treg in our cohort of patients. Sorafenib, but not sunitinib,
      leads to an early and sustained increase in Treg in PB of mRCC patients. In
      immunoresponsive tumors such as RCC, immunological effects of kinase inhibitors
      are particularly relevant for the design of combination trials with
      immunotherapeutic agents. Our study suggests that sorafenib should be avoided in
      such a therapeutic setting.

PMID- 22156796
TI  - Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and
      systemic metronomic combination therapy.
AB  - The prognosis of recurrent medulloblastoma is dismal, with a median survival of
      less than 1 year. Our patient was initially diagnosed with high-risk
      medulloblastoma when he was 14 years old. He had a recurrence 18 months after the
      end of therapy. Recurrence treatment consisted of 13 intrathecal applications of
      liposomal cytarabine over an 18-month period, and oral metronomic antiangiogenic
      therapy with thalidomide, celecoxib, and etoposide. Side effects from the
      intrathecal treatment were most likely related to arachnoiditis despite prolonged
      prophylaxis with steroids. He also developed partial hearing loss. Neutropenia
      was the main side effect of the metronomic therapy. He remains alive, with a good
      quality of life and without evidence of disease 34 months from the start of
      recurrence therapy. This combination of local antineoplastic and systemic
      antiangiogenic therapy seems to be promising for recurrent medulloblastoma.
      However, more patients and standardized protocols are needed to verify the
      benefit of this combination therapy and to define the correct duration of
      treatment.

PMID- 22156797
TI  - Signs of pneumoperitoneum.

PMID- 22156799
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of Agrobacterium and Rhizobium: minutes of the meeting, 7 September
      2010, Geneva, Switzerland.

PMID- 22156800
TI  - Human prostate cancer ZIP1/zinc/citrate genetic/metabolic relationship in the
      TRAMP prostate cancer animal model.
AB  - Prostate cancer is the second leading cause of cancer deaths among men. The
      availability of animal models that represent the events and factors that exist in
      the natural history and biology of human prostate cancer is essential in dealing
      with prostate cancer. In recent decades and presently, emphasis has been directed
      at the development and employment of prostate cancer induced in transgenic mice.
      However, the important consistent hallmark characteristic and event of decrease
      in zinc and citrate and downregulation of ZIP1 zinc transporter in prostate
      malignancy has not been studied or identified in any animal model. We
      investigated the status of these parameters in TRAMP tumors as compared with
      human prostate cancer. The results show that citrate levels are markedly
      decreased in the developing and advancing stages of malignancy in TRAMP. Zinc
      levels are also decreased and ZIP1 transporter is lost in TRAMP tumors. In vitro
      studies show that zinc treatment of TRAMP C2 cells exhibits cytotoxic effects.
      Collectively, these results mimic the ZIP1, zinc, and citrate status and
      relationship that exist in human prostate cancer. This is the first report that
      establishes the existence of the human prostate zinc/citrate hallmark
      characteristic and relationship in an animal model. It now appears that the TRAMP
      model will be suitable for studies relating to the implications and role of zinc-
      and citrate-related metabolism in the development and progression of human
      prostate cancer.

PMID- 22156801
TI  - Current world literature.

PMID- 22156803
TI  - Triggering receptor expressed on myeloid cells type 1 as a potential therapeutic
      target in sepsis.
AB  - Excessive and unregulated inflammation contributes to multiorgan failure and
      death in sepsis. Triggering receptor expressed on myeloid cells type 1(TREM-1) is
      expressed on neutrophils and monocytes and is upregulated in the presence of
      bacterial pathogens. Engagement of TREM-1 results in increased expression of
      proinflammatory chemokines and cytokines and amplifies the inflammatory response.
      In this article, we will review the structure and signaling pathway of TREM-1 and
      review the role of TREM-1 and soluble TREM-1 in the inflammatory response during
      sepsis. Based on these studies, modulation of the TREM-1 signaling pathway has
      been suggested as a potential therapeutic strategy for the treatment of sepsis,
      to dampen the inflammatory response without interrupting the ability of the host
      to clear pathogens. This basic science research may someday lead to other
      treatments for sepsis and other diseases.

PMID- 22156805
TI  - Amiodarone use to prevent postoperative atrial fibrillation after cardiac
      surgery.
AB  - Atrial fibrillation is the most common complication occurring after coronary
      artery bypass graft surgery. The purpose of this article was to examine the
      incidence of, risk factors related to, and complications caused by postoperative
      atrial fibrillation. The pathophysiology and treatment of atrial fibrillation and
      postoperative atrial fibrillation will also be discussed.

PMID- 22156807
TI  - Upstream palliative care for the patient with a left ventricular assist device as
      destination therapy.
AB  - Left ventricular assist devices are increasingly being used as destination
      therapy for heart failure patients who are not candidates for a heart transplant.
      The palliative care needs of this population will continue to grow as devices
      become more effective and more left ventricular assist devices are implanted. As
      part of an integrated multidisciplinary team, nurses are vital to successful
      outcomes for these patients.

PMID- 22156809
TI  - When the patient and family just do not get it: overcoming low health literacy in
      critical care.
AB  - Low health literacy in patients and families has been called a silent epidemic.
      Although there is a great deal of literature to assist nurses to address health
      literacy problems, little has focused on overcoming low health literacy in
      critical care. This article provides a definition of health literacy, explores
      how Baker's health literacy model can be applied to the critical care environment
      using Osborne's practical strategies, and presents 2 patient scenarios in which
      addressing low health literacy changed the outcomes for the patient and family.
      The article concludes with recommendations for critical care nurses to overcome
      low health literacy of patients and their families.

PMID- 22156811
TI  - Clinician satisfaction with computer decision support in the intensive care unit.
AB  - The purpose of this study was to determine baseline user satisfaction for 2
      computer decision support systems (DSSs) with demonstrated improvement in patient
      outcome used in a burn intensive care unit. We conducted a survey of staff
      members of a 16-bed burn intensive care unit (n = 82) using a written, anonymous
      questionnaire to determine satisfaction for 2 DSSs: a commercial glycemic
      management system and software program to guide initial burn fluid resuscitation.
      Staff members are not yet convinced of a positive correlation between DSS
      technology and patient outcomes. We suggest user satisfaction may be generally
      improved for DSS with concentration in the areas of interface, information, and
      communication.

PMID- 22156812
TI  - Exploration of the association between professional interactions and emotional
      distress of intensive care unit nursing personnel.
AB  - : Several studies provide evidence for the association between the quality of
      collaboration among intensive care unit (ICU) professionals and patients'
      outcomes, as well as nurses' moral distress and professional satisfaction.
      However, potential associations between collaboration and nurses' mental health
      indices have not been explored. The aim of this descriptive correlational study
      was to investigate the degree of satisfaction from interaction among ICU nursing
      personnel, as well as between ICU nursing personnel and physicians, and potential
      associations with ICU nursing personnel's anxiety symptoms. The sample consisted
      of ICU nursing personnel from 11 adult general hospitals in Greece (n = 229).
      Hamilton's Anxiety scale was applied for the quantitative assessment of anxiety
      symptoms and Stamps' Index of Work Satisfaction for the appraisal of nursing
      personnel's satisfaction from professional interactions. Demographic, vocational,
      and educational data were also recorded. Descriptive statistics were explored,
      and group comparisons, correlation, and regression analysis were used. The
      average satisfaction score from interaction among nursing personnel was moderate
      to high (5.3 [SD, 1.0]) and from nurse-to-physician interaction was moderate (4.0
      [SD, 1.4]) (scale range, 1-7). The score of satisfaction from nurse-to-physician
      interaction was negatively mildly correlated with participants' (a) total anxiety
      score (tau = -0.160, P = .001), (b) tension (tau = -0.125, P = .015), and (c)
      depressive symptoms (tau = -0.148, P = .005). Weak negative correlations were
      detected between satisfaction from interaction among nursing personnel and
      participants' (a) total anxiety state (tau = -0.139, P = .003), (b) tension (tau
      = -0.137, P = .008), and (c) sleep disturbances (tau = -0.150, P = .003).
      Overall, female respondents had higher levels of anxiety symptoms than male
      respondents (Mann-Whitney U, P = .007). Satisfaction from professional
      interaction was not a strong predictor of anxiety symptoms among ICU nursing
      personnel (R2 = 0.046, ?0.15). Nursing personnel in Greek ICUs seem to be
      satisfied with the quality of relationships among them, as well as with
      physicians. Despite that anxiety symptoms associate with the degree of
      satisfaction from professional interaction, the latter may not be a significant
      indicator of ICU nurses' well-being. Further qualitative research is needed to
      identify mediating factors.

PMID- 22156813
TI  - Explanatory models of heart failure etiology.
AB  - Chronic health failure is a leading cause of hospital readmissions and is
      reaching epidemic proportions in the United States. Explanatory models of illness
      can provide insight about how people with heart failure perceive their etiology
      of heart failure. Six themes were found in this descriptive, qualitative study to
      explore the perceived origin of heart failure in 50 participants. Forty percent
      of the people were unaware of why they had the diagnosis. Misconceptions and
      misinformation were common, including confusion about whether the symptoms
      themselves caused the disease.

PMID- 22156815
TI  - Family presence on rounds: a systematic review of literature.
AB  - Family-centered care has become the new trend in the health care field that
      involves honoring the patient and families' perspectives and choices and
      supporting them in participating in care and decision making at whatever level
      they choose. Family presence on rounds is one of the guidelines instituted for
      evidence-based best practices for support of family in the delivery of patient
      centered care in the intensive care unit (ICU) but identified as the least
      studied among all the other aspects of family-centered care in the ICU. From 1988
      to 2010, only 1 research study on family presence was conducted in an adult ICU.
      The purpose of this article was to review research studies related to family
      presence on medical rounds; reviews that focus on both adults and pediatric
      patients in the critical and noncritical care settings are also included.

PMID- 22156817
TI  - A guest editorial: Last word: patient- and family-centered care.

PMID- 22156819
TI  - Strategies for decreasing vascular complications in diagnostic cardiac
      catheterization patients.
AB  - Vascular complications are the most common type of complication after a cardiac
      catheterization. These include hematoma, pseudoaneurysm, arteriovenous fistula,
      peripheral artery occlusion and dissection, and retroperitoneal bleeding. The
      Pennsylvania Patient Safety Authority reports that nearly half the medical errors
      that occurred between June 2004 and December 2006 were cardiac catheterization
      complications, many of which were vascular related. The American College of
      Cardiology's National Cardiovascular Data Registry benchmark for vascular
      complications incidence is less than 1% for diagnostic catheterizations and less
      than 3% for percutaneous coronary intervention. The need to search for strategies
      to decrease vascular complication in diagnostic cardiac catheterization patients
      was a priority.

PMID- 22156821
TI  - Invasive pneumococcal disease in HIV-infected adults: clinical changes after the
      introduction of the pneumococcal conjugate vaccine in children.
AB  - BACKGROUND: Few data exist on the implications of widespread use of 7-valent
      pneumococcal conjugate vaccine in children in the invasive pneumococcal disease
      (IPD) in HIV-infected adults. We conducted a multicenter study to analyze
      differences in clinical presentation of IPD between HIV-infected and non-HIV
      infected adults in the prevaccine and postvaccine era. METHODS: Study of all
      cases of IPD in HIV-infected adults diagnosed since 1996 to 2010. Episodes were
      classified into prevaccine (1996-2001), early postvaccine (2002-2004), and late
      postvaccine period (2005-2010). For each case, we identified an HIV-negative
      control patient with IPD matched by hospital, age, and vaccine period. RESULTS:
      Two hundred twenty-one episodes of IPD in HIV-infected patients were diagnosed.
      The incidence of IPD decreased from 7.81 to 3.69 episodes per 1000 patient-years
      (-53%; 95% confidence interval: -65% to -36%, P < 0.001) between prevaccine and
      late postvaccine period. There was an 81% (95% confidence interval: -88% to -69%,
      P < 0.001) decrease of IPD caused by vaccine serotypes. In late postvaccine
      period IPD in HIV-infected patients was associated to higher rates of respiratory
      failure (28.4% vs. 48.4%, P = 0.011), greater intensive care unit admission (8.2%
      vs. 21.7%, P = 0.02) and a higher need for mechanical ventilation (5.9% vs.
      16.3%, P = 0.033). In the prevaccine period, non-HIV-infected patients had a more
      severe illness than in those with HIV infection; however, these differences
      disappeared in the late postvaccine period. CONCLUSIONS: In the late postvaccine
      era, the incidence of IPD in HIV-infected patients has decreased, however,
      clinical presentation seems to have changed to a more severe illness. The
      widespread use of highly active antiretroviral therapy, polyssacharide vaccine,
      and 7-valent pneumococcal conjugate vaccine has contributed to these changes.

PMID- 22156822
TI  - Inverse correlation of initial CD8 lymphocyte count and CD4 lymphocyte response
      to combination antiretroviral therapy in treatment-naive HIV-infected patients.

PMID- 22156823
TI  - Discrepancies between WHO 2009 and IAS-USA 2009 lists for determining the rate of
      transmitted HIV-1 drug resistance: a prospective study.

PMID- 22156824
TI  - Emotional impact of premature aging symptoms in long-term treated HIV-infected
      subjects.

PMID- 22156825
TI  - The change in deep cervical flexor activity after training is associated with the
      degree of pain reduction in patients with chronic neck pain.
AB  - OBJECTIVES: Altered activation of the deep cervical flexors (longus colli and
      longus capitis) has been found in individuals with neck pain disorders but the
      response to training has been variable. Therefore, this study investigated the
      relationship between change in deep cervical flexor muscle activity and symptoms
      in response to specific training. METHODS: Fourteen women with chronic neck pain
      undertook a 6-week program of specific training that consisted of a
      craniocervical flexion exercise performed twice per day (10 to 20 min) for the
      duration of the trial. The exercise targets the deep flexor muscles of the upper
      cervical region. At baseline and follow-up, measures were taken of neck pain
      intensity (visual analogue scale, 0 to 10), perceived disability (Neck Disability
      Index, 0 to 50) and electromyography (EMG) of the deep cervical flexors (by a
      nasopharyngeal electrode suctioned over the posterior oropharyngeal wall) during
      performance of craniocervical flexion. RESULTS: After training, the activation of
      the deep cervical flexors increased (P<0.0001) with the greatest change occurring
      in patients with the lowest values of deep cervical flexor EMG amplitude at
      baseline (R(2)=0.68; P<0.001). There was a significant relationship between
      initial pain intensity, change in pain level with training, and change in EMG
      amplitude for the deep cervical flexors during craniocervical flexion (R(2)=0.34;
      P<0.05). DISCUSSION: Specific training of the deep cervical flexor muscles in
      women with chronic neck pain reduces pain and improves the activation of these
      muscles, especially in those with the least activation of their deep cervical
      flexors before training. This finding suggests that the selection of exercise
      based on a precise assessment of the patients' neuromuscular control and targeted
      exercise interventions based on this assessment are likely to be the most
      beneficial to patients with neck pain.

PMID- 22156826
TI  - A prospective study of pain experience in a neonatal intensive care unit of
      China.
AB  - OBJECTIVES: To assess pain burden in neonates during their hospitalization in
      China and thus provide evidence for the necessity of neonatal pain management.
      PATIENTS AND METHODS: The Neonatal Facial Coding System was used to evaluate pain
      in neonates. We prospectively collected data of all painful procedures performed
      on 108 neonates (term, 62; preterm, 46) recruited from admission to discharge in
      a neonatal intensive care unit of a university-affiliated hospital in China.
      RESULTS: We found that during hospitalization each preterm and term neonate was
      exposed to a median of 100.0 (range, 11 to 544) and 56.5 (range, 12 to 249)
      painful procedures, respectively. Most of the painful procedures were performed
      within the first 3 days. Preterm neonates, especially those born at 28 and 29
      weeks' gestational age, experienced more pain than those born at 30 weeks'
      gestation or later (P<0.001). Among those painful procedures, tracheal aspiration
      was the most frequently performed on preterm neonates, and intravenous
      cannulation was the most common for term neonates. Moreover, tracheal intubations
      and femoral venous puncture were found to be the most painful. Notably, none of
      the painful procedures was accompanied by analgesia. CONCLUSIONS: Neonates,
      particularly preterm neonates, were exposed to numerous invasive painful
      procedures without appropriate analgesia in hospitals in China. The potential
      long-term impacts of poorly treated pain in neonates call for a change in
      pediatric practice in China and in countries with similar practices.

PMID- 22156827
TI  - The pain quality response profile of pregabalin in the treatment of neuropathic
      pain.
AB  - OBJECTIVE: To identify and describe the response profile of pregabalin on the
      qualities of pain associated with peripheral neuropathy. METHODS: A post hoc
      analysis to examine the effects of pregabalin on pain quality in patients with
      moderate-to-severe peripheral neuropathic pain was performed using data from an
      enriched enrollment randomized withdrawal proof-of-concept study. Patients rated
      the quality of their pain experience using the Pain Quality Assessment Scale
      (PQAS) at baseline, after a 12-day titration period, after a 9-day maintenance
      period, and after a 19-day randomized withdrawal period. Pretitration to
      posttitration and prewithdrawal to postwithdrawal changes in PQAS paroxysmal,
      surface, and deep pain scale scores were examined. RESULTS: PQAS data were
      available for 99 of the 104 participants who entered all phases of the study.
      There were significant (P<0.006, Bonferroni adjusted for multiple tests)
      improvements pretitration to posttitration in all 3 PQAS subscales, with a
      greater effect on paroxysmal and deep pain than on surface pain. During the
      withdrawal phase, pregabalin was significantly (P<0.006) more effective than
      placebo for improvements in paroxysmal and surface pain only, although the
      pregabalin group continued to show numerical improvement in deep pain relative to
      placebo. DISCUSSION: Pregabalin had a greater effect on PQAS-assessed paroxysmal
      pain than on surface or deep pain in patients with peripheral neuropathy. The
      findings corroborate previous research demonstrating differential effects of
      analgesic drugs across pain qualities, further emphasizing the need to assess
      individual pain qualities in addition to overall pain intensity.

PMID- 22156828
TI  - Another intriguing application of hypothermia: and some words of caution.

PMID- 22156829
TI  - Supraglottic Merkel cell carcinoma: a "cannot intubate-cannot ventilate" trap.

PMID- 22156830
TI  - Strategies for distinguishing low-grade endometrioid and serous carcinomas of
      endometrium.
AB  - Distinction between endometrioid and serous carcinomas of the endometrium has
      important prognostic and therapeutic implications. Misdiagnosing a serous
      carcinoma as endometrioid can have significant consequences for the patient and
      pathologist. Although many cases are straightforward and easy to classify, there
      are occasional problematic cases. This review focuses on strategies that help
      differentiate between low-grade endometrioid carcinoma and serous carcinoma of
      the endometrium. We will discuss clinical, morphologic, and immunohistochemical
      differences between the 2 entities and provide practical tips for practicing
      pathologists when confronted with this differential diagnosis.

PMID- 22156831
TI  - Waldenstrom macroglobulinemia:  a review of the entity and its differential
      diagnosis.
AB  - The definition of Waldenstrom macroglobulinemia (WM), originally described in
      1944, has been refined substantially over time. The current fourth edition of the
      World Health Organization of lymphoid neoplasms, in large part, adopted criteria
      proposed for WM at a consensus conference in 2002. WM is defined as
      lymphoplasmacytic lymphoma involving the bone marrow associated with a serum
      immunoglobulin (Ig) M paraprotein of any concentration. Morphologically, WM is
      composed of a variable mixture of lymphocytes, plasmacytoid lymphocytes, and
      plasma cells. Immunophenotypically, the neoplastic cells express monotypic IgM
      and light chain: B lymphocytes express pan-B-cell antigens and surface Ig are
      usually negative for CD5 and CD10; and plasma cells are typically positive for
      CD138, CD38, CD45, cytoplasmic Ig, and CD19 (in a substantial subset of cases).
      The putative cell of origin of WM is a postantigen selected memory B-cell that
      has undergone somatic hypermutation. The most common cytogenetic abnormality in
      WM is del(6q), usually in the region 6q23-24.3, present in 40% to 50% of cases.
      IGH gene translocations are rare and recurrent chromosomal translocations or gene
      aberrations have not been identified in WM. Here, we provide a historical
      perspective of WM, review clinical and pathologic aspects of the disease as it is
      currently defined, and discuss some practical issues in the differential
      diagnosis of WM that pathologists encounter in the signout of cases.

PMID- 22156832
TI  - Lymphocytic colitis and collagenous colitis:  a review of clinicopathologic
      features and immunologic abnormalities.
AB  - Lymphocytic colitis (LC) and collagenous colitis (CC), 2 histologic forms of
      microscopic colitis, were recognized as rare disease entities 4 decades ago. An
      increasing body of evidence accumulated in the past 40 years reveals increasing
      incidence and prevalence rates, a wide spectrum of clinical presentations, and
      several histologic variants. Although several recent randomized clinical trials
      confirmed the efficacy of oral budesonide in treating LC and CC, disease relapse
      after a short-duration treatment is common. Despite their common clinical
      presentations and well-defined histologic diagnostic criteria, there are only few
      studies on the immunologic abnormalities in colonic tissue. The aim of this
      review is to (1) familiarize the pathologists in general practice with
      histomorphology of LC and CC, including the rare histologic variants and the
      clinical implication associated with these 2 diagnoses, (2) summarize the data
      from recent randomized clinical trials of oral budesonide, and (3) review
      immunological studies on colonic tissue. Overall, immunologic abnormalities of
      colonic tissue seem to explain for the histomorphologic features and the clinical
      symptomatology of LC and CC. Advances in the understanding of the underlying
      immunologic abnormalities in the colonic tissue may help develop novel and
      effective therapies for these 2 diseases.

PMID- 22156833
TI  - Molecular classification of estrogen receptor-positive/luminal breast cancers.
AB  - Estrogen receptor (ER)-positive breast cancer is the most prevalent subtype of
      invasive breast cancers. Patients with ER-positive breast cancers have variable
      clinical outcomes and responses to endocrine therapy and chemotherapy. With the
      advent of microarray-based gene expression profiling, unsupervised analysis
      methods have resulted in a classification of ER-positive disease into subtypes
      with different outcomes (ie, luminal A and luminal B); subsequent studies have
      demonstrated that these subtypes have different patterns of genetic aberrations
      and outcome. Studies based on supervised methods of microarray analysis have led
      to the development of prognostic gene signatures that identify a subgroup of ER
      positive breast cancer patients with excellent outcome, who could forego
      chemotherapy. Despite the excitement with these approaches, several lines of
      evidence have demonstrated that the subclassification of ER-positive cancers and
      the prognostic value of gene signatures is largely driven by the expression
      levels of proliferation-related genes and that proliferation markers, such as
      Ki67, may provide equivalent prognostic information to that provided by gene
      signatures. In this review, we discuss the contribution of gene expression
      profiling to the classification of ER-positive breast cancer, the role of
      prognostic and predictive signatures, and the potential stratification of ER
      positive disease according to their dependency on the phosphatidylinositol 3
      kinase pathway.

PMID- 22156834
TI  - Pediatric fibroblastic and myofibroblastic lesions.
AB  - Fibrous lesions of infancy and childhood are a heterogeneous group of entities
      composed predominantly of fibroblasts and myofibroblasts, ranging from reactive
      lesions to neoplasms with a range of malignant potential. Although rare, their
      correct recognition by histopathology is important clinically as they exhibit a
      wide range of behaviors and may be associated with distinct underlying syndromes.
      Contributions from molecular diagnostics have enabled more accurate diagnosis,
      and have changed our concepts of some tumor types. In this review, we discuss the
      clinicopathologic spectrum of fibroblastic and myofibroblastic lesions of
      childhood and adolescence.

PMID- 22156835
TI  - Napsin A expression in lung and kidney neoplasia: a review and update.
AB  - Napsin A is an aspartic protease present in the epithelial cells of the lung and
      kidney. Recent studies have shown that, in lung tumors, napsin A expression is
      restricted to lung adenocarcinomas, whereas among renal tumors, it is frequently
      expressed in renal cell carcinomas, especially the papillary and clear cell
      subtypes. Owing to its restricted expression, napsin A is a useful marker that
      can assist in the diagnosis of both lung adenocarcinomas and renal cell
      carcinomas.

PMID- 22156836
TI  - Creating a survey to assess physicians' adoption of health information
      technology.
AB  - Information on state-level health information technology (HIT) adoption will
      become increasingly important with the implementation of incentive payments to
      accelerate uptake. Recognizing this, the Rhode Island Department of Health
      selected physician HIT adoption as a subject for its legislatively mandated
      quality reporting program. This article discusses the state's process for
      developing HIT adoption measures, including the importance of stakeholder
      involvement in the development of a survey and the difficulty of accurately
      defining electronic medical record (EMR) adoption. This article describes the
      challenges in defining "true" EMRs, which may be addressed, in part, by ensuring
      local consensus about EMR measures and by piloting the survey and measures, prior
      to public reporting or the calculation of a statewide baseline. It also presents
      results from the 2009 administration of this survey to all 3,883 Rhode Island
      licensed physicians providing direct patient care.

PMID- 22156837
TI  - Do doctors contribute to the social patterning of disease? The case of
      race/ethnic disparities in diabetes mellitus.
AB  - Data from the Boston Area Community Health Survey show that both undiagnosed
      signs and symptoms and diagnosed type 2 diabetes mellitus (T2DM) are patterned by
      socioeconomic status (SES). Such patterning is corroborated by National Health
      and Nutrition Examination Survey data for diagnosed T2DM. Complementary data from
      an experiment concerning clinical decision making show T2DM is patterned by
      race/ethnicity, following diagnosis by a physician. Undiagnosed signs and
      symptoms of T2DM in the community are patterned by SES (rather than
      race/ethnicity), but following diagnosis by primary care physicians they are
      patterned more by race/ethnicity (rather than by SES). Race/ethnicity and SES in
      the United States are almost totally confounded, such that measuring one is
      essentially also measuring the other. Physician patterning of T2DM by
      race/ethnicity, however, motivates the search for genetic and biophysiologic
      explanations and distracts attention from the more important contribution of SES
      circumstances to the prevalence of diabetes mellitus.

PMID- 22156838
TI  - Reversible cerebral vasoconstriction syndrome in a 35-year-old woman following
      hysterectomy and bilateral salpingo-oophorectomy.
AB  - INTRODUCTION: Reversible cerebral vasoconstriction syndromes (RCVS) have been
      documented to take place after an inciting event or illness. They present with
      headache, altered mental status and focal neurologic findings. The differential
      diagnosis includes primary angiitis of the central nervous system (PACNS) but one
      major clinical difference is that the symptoms of RCVS usually resolve within
      days or weeks whereas PACNS is often fatal. Females of childbearing age are most
      commonly affected with RCVS. Cases of reversible vasculopathy have also been
      reported in menopausal women. The hormonal and physiologic changes that take
      place during the postpartum period and menopause may not be very different from
      those that occur after a hysterectomy and oophorectomy. METHODS: A case is
      presented of a 35-year-old woman who underwent a hysterectomy with bilateral
      salpingo-oophorectomy and then began experiencing severe headaches, visual
      changes and hemi-sensory loss. Physical examination, imaging and laboratory
      findings were descriptive of RCVS, and the patient's rapid recovery was
      consistent with the usual disease progression of a reversible vasculopathy.
      CONCLUSION: A reversible cerebral vasoconstriction syndrome may occur in some
      circumstances after a hysterectomy with bilateral salpingo-oophorectomy. The
      mechanisms involved in the development of this condition are explained by current
      research concerning effects on the vasculature of sudden drops in estrogens and
      progesterones. More studies are required to further establish the
      pathophysiology, diagnosis and treatment of this condition.

PMID- 22156840
TI  - HIV vaccine development at the turn of the 21st century.
AB  - PURPOSE OF REVIEW: To review the status of HIV vaccine development RECENT
      FINDINGS: Since the discovery of HIV-1 in the early 1980s considerable effort has
      been exerted to develop a prophylactic vaccine, with relatively meagre results.
      The absence of natural immunity has proven to be a major stumbling block in
      identifying a mechanism of protection. However, many different animal models have
      contributed to our knowledge of the pathogenesis of infection and of the variety
      of antibody and cellular responses that are induced by the virus. The knowledge
      created by the studies in nonhuman primates, although important, has not
      necessarily been proven applicable in humans and thus an effective vaccine has
      been elusive. The combined lack of a fully predictive animal model ('mice lie and
      monkeys exaggerate') and lack of defined markers of immune protection against HIV
      1 necessitate that HIV vaccines be tested directly for efficacy in phase IIb/III
      efficacy trials in human volunteers at risk. A trial conducted in Thailand showed
      moderate but significant protection against infection. SUMMARY: The process of
      HIV vaccine development is slow, costly and tedious. However, recent preclinical
      and clinical results have fortunately been a source of renewed optimism in the
      field.

PMID- 22156839
TI  - Systems vaccinology:  its promise and challenge for HIV vaccine development.
AB  - PURPOSE OF REVIEW: The use of systems biology approaches to understand and
      predict vaccine-induced immunity promises to revolutionize vaccinology. For
      centuries vaccines were developed empirically, with very little understanding of
      the mechanisms by which they mediate protective immunity. The so-called systems
      vaccinology approach employs high-throughput technologies (e.g. microarrays, RNA
      seq and mass spectrometry-based proteomics and metabolomics) and computational
      modeling to describe the complex interactions between all the parts of immune
      system, with a view to elucidating new biological rules capable of predicting the
      behavior of the system. RECENT FINDINGS: Systems biology successfully applied to
      yellow-fever and influenza vaccines has led to the discovery of signatures that
      predict vaccine immunogenicity, and promises to advance basic immunology research
      by providing novel mechanistic insights about immune regulation. However a major
      challenge of systems vaccinology concerns the analyses and interpretation of the
      large and noisy data sets generated by high-throughput techniques. Overcoming
      these issues, we envision that systems vaccinology will have a potential impact
      on vaccine development, including HIV vaccines. SUMMARY: High-throughput
      technologies allow the investigation of vaccine-induced immune responses at
      system and molecular levels. These are currently being used to unravel new
      molecular insights about the immune system, and are on the verge of being
      integrated into clinical trials to enable rational vaccine design and
      development.

PMID- 22156841
TI  - Probing the T-cell receptor repertoire with deep sequencing.
AB  - PURPOSE OF REVIEW: To review major findings on the T-cell receptor (TCR)
      repertoire diversity in response to several viral infections based on
      conventional methods of PCR, cloning and sequencing and to discuss their
      limitations in light of the recent methodological advances in deep sequencing.
      RECENT FINDINGS: Direct sequencing of TCR expressed by Ag-specific T cells
      isolated ex vivo has revealed that the TCR repertoire is not as restricted as
      previously estimated. Furthermore, analyses performed independently of the T-cell
      clonal hierarchy have brought to light an unexpected diversity. The choice of
      methods is critical to characterize the complexity of the repertoire. Recent
      advances in deep sequencing have uncovered the diversity of the TCR repertoire
      and shown that the size of the repertoire in naive and Ag-experienced memory T
      cells is three-fold to 15-fold larger than formerly estimated. Interestingly, the
      TCR complementary determining region 3 sequences are not randomly selected and a
      certain degree of shared TCR repertoire has been observed between different
      individuals. SUMMARY: Deep sequencing is a major methodological advance allowing
      more accurate molecular characterization of the TCR repertoire. In the near
      future, such technologies will further contribute to delineate the complexity of
      pathogen-specific T-cell response and help defining correlates of a protective
      immunity.

PMID- 22156842
TI  - Systems biology in the development of HIV vaccines.
AB  - PURPOSE OF REVIEW: In the present review, we will provide the scientific
      rationale for applying systems biology to the development of vaccines and
      particularly HIV vaccines, the predictive power of systems biology on the vaccine
      immunological profile, the correlation between systems biology and the
      immunological functional profiles of different candidate vaccines, and the value
      of systems biology in the selection process of identifying the best-in-class
      candidate vaccines and in the decision process to move into in-vivo evaluation in
      clinical trials. RECENT FINDINGS: Systems biology has been recently applied to
      the characterization of the protective yellow fever vaccine YF17D and of seasonal
      flu vaccines. This has been instrumental in the identification of the components
      of the immune response that need to be stimulated by the vaccine in order to
      generate protective immunity. It is worth noting that a systems biology approach
      is currently being performed to identify correlates of immune protection of the
      RV144 Thai vaccine, the only known vaccine that showed modest protection against
      HIV reacquisition. SUMMARY: Systems biology represents a novel and powerful
      approach to predict the vaccine immunological profile, to identify the protective
      components of the immune response, and to help in the selection process of the
      best-in-class vaccines to move into clinical development.

PMID- 22156843
TI  - Overcoming limitations in the systems vaccinology approach:  a pathway for
      accelerated HIV vaccine development.
AB  - PURPOSE OF REVIEW: There remains a pressing need for an efficacious vaccine to
      combat HIV. The burgeoning fields of systems biology and innate immunity, as
      harnessed in systems vaccinology, promise to accelerate the discovery process and
      meet this need. RECENT FINDINGS: The tools of systems biology are increasingly
      employed to define innate immune responses to vaccination and thereby unmask
      early signaling events that control induced adaptive immunity. These studies
      involve a wide array of measurements, including transcriptomics and proteomics,
      and a wide array of biological systems, from in-vitro stimulated murine innate
      immune cells to whole blood collected from vaccinated human donors. Each
      measurement and each system offers unique insights as well as special limitations
      and challenges. SUMMARY: A holistic consideration of the models available for
      intensive HIV systems vaccinology analysis identifies a suite of interlocking
      opportunities and constraints. Although the murine system enables detailed
      mechanistic analysis, vaccine efficacy cannot be assessed in this model. Systems
      analysis of blood donated by vaccinated humans permits identification of
      immunogenicity signatures and biomarkers, but deriving direct mechanisms from
      these indirect measurements is precarious. The goals of HIV systems vaccinology
      may be best met by judicious integration of in vitro, in vivo (murine and
      nonhuman primate), and human clinical analyses.

PMID- 22156844
TI  - Deconvolving heterogeneity in the CD8+ T-cell response to HIV.
AB  - PURPOSE OF REVIEW: This review will discuss the use of systems biology approaches
      to dissect the heterogeneity of the HIV-specific CD8+ T-cell response. RECENT
      FINDINGS: New experimental approaches have allowed complex phenotypes of
      individual cells present in the human antigen-specific CD8+ T-cell response to be
      characterized. Genome-wide measurements of gene expression in antigen-specific T
      cells have created broad molecular phenotypes of the T-cell response to HIV.
      Pattern recognition algorithms to discover new subclasses of samples in
      microarray datasets are becoming increasingly sophisticated. Together, these
      advances now allow the heterogeneity of the T-cell response to HIV to be
      unraveled. SUMMARY: The phenotype of antigen-specific T cells responding to
      pathogens like HIV in humans is seen as much 'noisier' than in animal models of
      infection. However, applying new systems biology tools may provide an opportunity
      to identify the sources of this 'noise' as novel, biologically distinct
      subclasses of the CD8+ T-cell response to HIV.

PMID- 22156845
TI  - Dynamics of innate immunity are key to chronic immune activation in AIDS.
AB  - PURPOSE OF REVIEW: We propose here that the dynamics rather than the structure of
      cellular and viral networks play a determining role in chronic immune activation
      of HIV-infected individuals. A number of novel avenues of experimental analysis
      and modeling strategies are discussed to conclusively address these network
      dynamics in the future. RECENT FINDINGS: Recent insights into the molecular
      dynamics of immune activation and its control following simian immunodeficiency
      virus (SIV) infection in natural host primates has provided possible alternate
      interpretations of SIV and HIV pathogenesis. Concomitant with insights gained in
      other host-pathogen systems, as well as an increased understanding of innate
      immune activation mechanisms, these observations lead to a new model for the
      timing of innate HIV immune responses and a possible primordial role of this
      timing in programming chronic immune activation. SUMMARY: Chronic immune
      activation is today considered the leading cause of AIDS in HIV-infected
      individuals. Systems biology has recently lent arguments for considering chronic
      immune activation a result of untimely innate immune responses by the host to the
      infection. Future strategies for the analysis, comprehension, and incorporation
      of the dynamic component of immune activation into HIV vaccination strategies are
      discussed.

PMID- 22156846
TI  - An open-ended plea for the development of a global database of HIV vaccine
      responses.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe a critical need of
      the HIV research community for a globally accessible database of HIV vaccine
      responses that stores data from multiple assay platforms in the form of lists of
      correlates of immune protection and vaccine efficacy. This is not a detailed
      review but a first step toward developing a dialogue among investigators and
      funding organizations to build upon existing resources to efficiently develop a
      HIV vaccine response and correlates database. We also discuss examples of
      databases that complement our needs and could be integrated into our proposed
      database requirements. RECENT FINDINGS: Several vaccine-related databases that
      store information at the study level currently exist, however, at the present
      time, a correlates of immune protection database does not exist. SUMMARY: Here,
      we discuss the scientific climate surrounding HIV vaccine development with the
      evolution of systems biology approaches, the problems at hand for analyzing and
      harmonizing datasets generated from preclinical and clinical studies, and the
      curation and accessibility of useful information to model outcomes. We also
      compare key database requirements of a few existing globally accessible databases
      and provide several illustrative correlate database submission and utilization
      examples.

PMID- 22156847
TI  - What is the impact of home-based HIV counseling and testing on the clinical
      status of newly enrolled adults in a large HIV care program in Western Kenya?
AB  - BACKGROUND: This article describes the effect point of entry into the human
      immunodeficiency virus (HIV) care program had on the clinical status of adults
      presenting for the first time to USAID-AMPATH (US Agency for International
      Development-Academic Model Providing Access to Healthcare) Partnership clinics
      for HIV care. METHODS: All patients aged >= 14 years enrolled between August 2008
      and April 2010 were included. Points of entry to USAID-AMPATH clinics were home
      based counseling and testing (HBCT), provider-initiated testing and counseling
      (PITC), HIV testing in the tuberculosis clinic, and voluntary counseling and
      testing (VCT). Tests for trend were calculated, and multivariable logistic
      regression was used to compare the effect of HBCT versus other points of entry on
      primary outcomes controlling for age and sex. RESULTS: There were 19,552 eligible
      individuals. Of these, 946 tested in HBCT, 10,261 in VCT, 8073 in PITC, and 272
      in the tuberculosis clinic. The median (interquartile range) enrollment CD4 cell
      counts among those who tested HIV positive was 323 (194-491), 217 (87-404), 190
      (70-371), and 136 cells/mm(3) (59-266) for HBCT, VCT, PITC, and the tuberculosis
      clinic, respectively (P < .001). Compared with those patients whose HIV infection
      was diagnosed in the tuberculosis clinic, those who tested positive in HBCT were,
      controlling for age and sex, less likely to have to have World Health
      Organization stage III or IV HIV infection at enrollment (adjusted odds ratio
      [AOR], 0.04; 95% confidence interval [CI], .03-.06), less likely to enroll with a
      CD4 cell count of <200 cells/mm(3) (AOR, 0.20; 95% CI, .14-.28), and less likely
      to enroll into care with a chief complaint (AOR, 0.08; 95% CI, .05-.12).
      CONCLUSIONS: HBCT is effective at getting HIV-infected persons enrolled in HIV
      care before they become ill.

PMID- 22156848
TI  - Infant pertussis: what to do next?

PMID- 22156849
TI  - Home-based HIV counseling and testing as a gateway to earlier initiation of
      antiretroviral therapy.

PMID- 22156850
TI  - The number needed to vaccinate to prevent infant pertussis hospitalization and
      death through parent cocoon immunization.
AB  - BACKGROUND: Parental immunization has been recommended as a "cocoon" strategy to
      prevent serious pertussis outcomes in early infancy. We illustrate the high
      number needed to vaccinate (NNV) for this program based on recent epidemiologic
      data from the provinces of Quebec and British Columbia (BC), Canada. METHODS:
      Surveillance trends were summarized for the period 1990-2010. Hospitalization,
      intensive care unit (ICU) admission, and mortality data were compiled from 2000
      to 2009. The proportion of infant pertussis attributed to a parent was estimated
      at 35%, explored up to 55%. Adult vaccine efficacy (VE) was estimated at 85%. The
      NNV was calculated as [2 parents/(parent-attributable infant risk * parent VE)].
      To capture at least 1 recent cyclical peak, NNV was derived for the period 2005
      2009 and explored for peak/trough years. RESULTS: Substantial decline has
      occurred in pertussis incidence across all age groups including infants, reaching
      a 20-year nadir in 2010 in both provinces. For the period 2005-2009, the risk of
      infant hospitalization and ICU admission was 57 and 7, respectively, per 100 000
      in Quebec and 33 and 7, respectively, per 100 000 in BC. In both provinces the
      risk of infant pertussis-related death over that period was <0.5 per 100 000. The
      NNV for parental immunization was at least 1 million to prevent 1 infant death,
      approximately 100 000 for ICU admission, and >10 000 for hospitalization.
      CONCLUSIONS: In the context of low pertussis incidence, the parental cocoon
      program is inefficient and resource intensive for the prevention of serious
      outcomes in early infancy. Regions contemplating the cocoon program should
      consider the NNV based on local epidemiology.

PMID- 22156851
TI  - Is central venous catheter tip colonization with Pseudomonas aeruginosa a
      predictor for subsequent bacteremia?

PMID- 22156852
TI  - Use of a rapid test of pneumococcal colonization density to diagnose pneumococcal
      pneumonia.
AB  - BACKGROUND: There is major need for a more sensitive assay for the diagnosis of
      pneumococcal community-acquired pneumonia (CAP). We hypothesized that
      pneumococcal nasopharyngeal (NP) proliferation may lead to microaspiration
      followed by pneumonia. We therefore tested a quantitative lytA real-time
      polymerase chain reaction (rtPCR) on NP swab samples from patients with pneumonia
      and controls. METHODS: In the absence of a sensitive reference standard, a
      composite diagnostic standard for pneumococcal pneumonia was considered positive
      in South African human immunodeficiency virus (HIV)-infected adults hospitalized
      with radiographically confirmed CAP, if blood culture, induced good-quality
      sputum culture, Gram stain, or urinary Binax demonstrated pneumococci. Results of
      quantitative lytA rtPCR in NP swab samples were compared with quantitative colony
      counts in patients with CAP and 300 HIV-infected asymptomatic controls. RESULTS:
      Pneumococci were the leading pathogen identified in 76 of 280 patients with CAP
      (27.1%) using the composite diagnostic standard. NP colonization density measured
      by lytA rtPCR correlated with quantitative cultures (r = 0.67; P < .001). The
      mean lytA rtPCR copy number in patients with pneumococcal pneumonia was 6.0
      log(10) copies/mL, compared with patients with CAP outside the composite standard
      (2.7 log(10) copies/mL; P < .001) and asymptomatic controls (0.8 log(10)
      copies/mL; P < .001). A lytA rtPCR density >=8000 copies/mL had a sensitivity of
      82.2% and a specificity of 92.0% for distinguishing pneumococcal CAP from
      asymptomatic colonization. The proportion of CAP cases attributable to
      pneumococcus increased from 27.1% to 52.5% using that cutoff. CONCLUSIONS: A
      rapid molecular assay of NP pneumococcal density performed on an easily available
      specimen may significantly increase pneumococcal pneumonia diagnoses in adults.

PMID- 22156853
TI  - Boceprevir and telaprevir in the management of hepatitis C virus-infected
      patients.
AB  - Recent approval of direct-acting antiviral agents (DAAs) against hepatitis C
      virus (HCV) offers a major advance in the management of HCV infection. These
      DAAs, boceprevir and telaprevir, when given with pegylated interferon alfa (Peg
      IFN) and ribavirin (RBV), result in a much higher sustained virologic response
      rate compared with Peg-IFN and RBV. The DAA-containing regimens are approved for
      HCV genotype 1 infection in HCV treatment-naive and HCV treatment-experienced
      patients. In this review, we present an overview of pharmacology, efficacy,
      adverse events, and emergence of resistance-associated variants with the use of
      these agents. As with all drugs, especially newly approved drugs, clinicians must
      consult the package insert for detailed prescribing information, list of all
      reported adverse events, contraindications, and drug interactions.

PMID- 22156854
TI  - Fidaxomicin: a novel macrocyclic antibiotic approved for treatment of Clostridium
      difficile infection.
AB  - Fidaxomicin, a nonabsorbed macrocyclic compound, is the first antimicrobial agent
      approved by the FDA for the treatment of Clostridium difficile infection (CDI) in
      adults over the last 25 years. It is bactericidal, and its mechanism of action
      relates to inhibition of a RNA polymerase at a site distinct from where
      rifamycins interact. Fidaxomicin, 200 milligrams by mouth twice daily, is not
      inferior to vancomycin, 125 milligrams by mouth 4 times daily, for treatment of
      CDI as determined by clinical response after 10 days of treatment and is superior
      to vancomycin for sustained response without recurrence 25 days after treatment
      completion. These results are a significant advance in the treatment of CDI and
      herald the development of narrow-spectrum anti-C. difficile agents that
      relatively spare the indigenous fecal microbiota. Continued vigilance for the
      development of resistance and unanticipated side affects will be important as the
      drug is introduced into clinical practice.

PMID- 22156855
TI  - Paradoxical responses after start of antimicrobial treatment in Mycobacterium
      ulcerans infection.
AB  - BACKGROUND:  Antimicrobial killing in mycobacterial infections may be accompanied
      by (transient) clinical deterioration, known as paradoxical reaction. To search
      for patterns reflecting such reactions in the treatment of Buruli ulcer
      (Mycobacterium ulcerans infection), the evolution of lesions of patients treated
      with antimicrobials was prospectively assessed. METHODS:  The lesion size of
      participants of the BURULICO antimicrobial trial (with lesions <=10 cm cross
      sectional diameter) was assessed by careful palpation and recorded by serial
      acetate sheet tracings. Patients were treated with antimicrobials for 8 weeks.
      For the size analysis, participants whose treatment had failed, had skin
      grafting, or were coinfected with human immunodeficiency virus were excluded. For
      every time point, surface area was compared with the previous assessment. A
      generalized additive mixed model was used to study lesion evolution.
      Nonulcerative lesions were studied using digital images recording possible
      subsequent ulceration. RESULTS:  Of 151 participants, 134 were included in the
      lesion size analysis. Peak paradoxical response occurred at week 8; >30% of
      participants showed an increase in lesion size as compared with the previous
      (week 6) assessment. Seventy-five of 90 (83%) of nonulcerative lesions ulcerated
      after start of treatment. Nine participants developed new lesions during or after
      treatment. All lesions subsequently healed. CONCLUSIONS:  After start of
      antimicrobial treatment for Buruli ulcer, new or progressive ulceration is common
      before healing sets in. This paradoxical response, most prominent at the end of
      the 8-week antimicrobial treatment, should not be misinterpreted as failure to
      respond to treatment. Clinical Trials Registration. ClinicalTrials.gov,
      NCT00321178.

PMID- 22156856
TI  - Liver fibrosis progression after acute hepatitis C virus infection in HIV
      positive individuals.
AB  - Fibrosis progression after acute hepatitis C virus (HCV) infection in human
      immunodeficiency virus (HIV)-infected patients with follow-up >9 months became
      similar to reported rates from studies in chronic HIV/HCV coinfection, as
      measured with transient elastometry. The duration of follow-up and serum alanine
      transaminase correlated with liver stiffness, and short follow-up resulted in
      high fibrosis progression rates.

PMID- 22156857
TI  - Patterns of Bordetella parapertussis respiratory illnesses: 2008-2010.
AB  - Clinical specimens from 9 states during 2008-2010 were tested by PCR for
      Bordetella pertussis and Bordetella parapertussis. Of the positive samples,
      13.99% were identified as B. parapertussis. It was concluded that B.
      parapertussis infections are more common than previously realized and contribute
      to cases thought to be vaccine failures.

PMID- 22156858
TI  - Differential clinical and virologic impact of hepatitis B virus genotypes B and C
      on HIV-coinfected patients receiving lamivudine-containing highly active
      antiretroviral therapy.
AB  - BACKGROUND:  The impact of hepatitis B virus (HBV) genotypes B and C on the
      clinical, immunologic, and virologic outcomes of human immunodeficiency virus
      (HIV)-infected patients with chronic HBV infection remains largely unknown.
      METHODS:  Between January 1997 and December 2008, we enrolled 96 HIV-infected
      patients with HBV genotype B coinfection and 49 with genotype C coinfection; the
      patients were followed prospectively until December 2010. Clinical and
      immunologic outcomes in the context of HBV genotypes as well as the emergence of
      HBV DNA mutations conferring lamivudine resistance (rtM204I/V) were determined.
      RESULTS:  The median duration of lamivudine-containing highly active
      antiretroviral therapy (HAART) was 2.80 years (interquartile range, 1.73-5.92
      years). The 2 groups of HIV-infected patients were comparable in age, sex,
      baseline HIV profiles, and liver function profiles. Compared with HIV-infected
      patients with HBV genotype C coinfection, those with genotype B coinfection had a
      higher risk of hepatitis flares (43.8% vs 26.5%; P = .04), liver disease-related
      death (9.4% vs 0%; P = .03), hepatitis B e antigen (HBeAg) seroconversion (61.5%
      vs 25.0%, P = .03), and development of lamivudine resistance (31.3% vs 12.2%; P <
      .0001). No differences were observed between the 2 groups in terms of the
      development of hyperbilirubinemia, cirrhosis, or virologic and immunologic
      responses to HAART. CONCLUSIONS:  Although therapeutic responses to long-term
      lamivudine-containing HAART were comparable between HIV-infected patients with
      HBV genotypes B and C coinfection, patients with genotype B coinfection were more
      likely to experience acute exacerbations of hepatitis, HBeAg seroconversion,
      lamivudine resistance, and liver disease-related death than those with genotype C
      coinfection.

PMID- 22156859
TI  - The isolation of spatial patterning modes in a mathematical model of juxtacrine
      cell signalling.
AB  - Juxtacrine signalling mechanisms are known to be crucial in tissue and organ
      development, leading to spatial patterns in gene expression. We investigate the
      patterning behaviour of a discrete model of juxtacrine cell signalling due to
      Owen & Sherratt (1998, Mathematical modelling of juxtacrine cell signalling.
      Math. Biosci., 153, 125-150) in which ligand molecules, unoccupied receptors and
      bound ligand-receptor complexes are modelled. Feedback between the ligand and
      receptor production and the level of bound receptors is incorporated. By
      isolating two parameters associated with the feedback strength and employing
      numerical simulation, linear stability and bifurcation analysis, the pattern
      forming behaviour of the model is analysed under regimes corresponding to lateral
      inhibition and induction. Linear analysis of this model fails to capture the
      patterning behaviour exhibited in numerical simulations. Via bifurcation
      analysis, we show that since the majority of periodic patterns fold subcritically
      from the homogeneous steady state, a wide variety of stable patterns exists at a
      given parameter set, providing an explanation for this failure. The dominant
      pattern is isolated via numerical simulation. Additionally, by sampling patterns
      of non-integer wavelength on a discrete mesh, we highlight a disparity between
      the continuous and discrete representations of signalling mechanisms: in the
      continuous case, patterns of arbitrary wavelength are possible, while sampling
      such patterns on a discrete mesh leads to longer wavelength harmonics being
      selected where the wavelength is rational; in the irrational case, the resulting
      aperiodic patterns exhibit 'local periodicity', being constructed from distorted
      stable shorter wavelength patterns. This feature is consistent with
      experimentally observed patterns, which typically display approximate short-range
      periodicity with defects.

PMID- 22156860
TI  - To operate or not to operate? Should functional outcomes after sigmoid colectomy
      for diverticulitis influence our decision making?

PMID- 22156861
TI  - Permanent ostomy after ileoanal pouch failure:  pouch in situ or pouch excision?
AB  - BACKGROUND: The risks and benefits of pouch excision and end ileostomy creation
      when compared to the alternative option of a permanent diversion with the pouch
      left in situ when restoration of intestinal continuity is not pursued for
      patients who develop pouch failure after IPAA have not been well characterized.
      OBJECTIVE: This study aimed to compare the early and long-term outcomes after
      permanent diversion with the pouch left in situ vs pouch excision with end
      ileostomy creation for pouch failure. DESIGN: This study is a retrospective
      review of prospectively gathered data. SETTINGS: This investigation was conducted
      at a tertiary center. PATIENTS: Patients with pouch failure who underwent a
      permanent ileostomy with the pouch left in situ and those who underwent pouch
      excision were included in the study. MAIN OUTCOME MEASURES: The primary outcomes
      measured were the perioperative outcomes and quality of life using the pouch and
      Short Form 12 questionnaires. RESULTS: One hundred thirty-six patients with pouch
      failure underwent either pouch left in situ (n = 31) or pouch excision (n = 105).
      Age (p = 0.72), sex (p = 0.72), ASA score (p = 0.22), BMI (p = 0.83), disease
      duration (p = 0.74), time to surgery for pouch failure (p = 0.053), diagnosis at
      pouch failure (p = 0.18), and follow-up (p = 0.76) were similar. The predominant
      reason for pouch failure was septic complications in 15 (48.4%) patients in the
      pouch left in situ group and 39 (37.1%) patients in the pouch excision group (p =
      0.3). Thirty-day complications, including prolonged ileus (p = 0.59), pelvic
      abscess (p = 1.0), wound infection (p = 1.0), and bowel obstruction (p = 1.0),
      were similar. At the most recent follow-up (median, 9.9 y), quality of life (p =
      0.005) and health (p = 0.008), current energy level (p = 0.026), Cleveland Global
      Quality of Life score (p = 0.005), and Short Form 12 mental (p = 0.004) and
      physical (p = 0.014) component scales were significantly higher after pouch
      excision than after pouch left in situ. Urinary and sexual function was similar
      between the groups. Anal pain (n = 4) and seepage with pad use (n = 8) were the
      predominant concerns of the pouch left in situ group on long-term follow-up. None
      of the 18 patients with pouch in situ, for whom information relating to long-term
      pouch surveillance was available, developed dysplasia or cancer. LIMITATIONS:
      This study was limited by its retrospective nature. CONCLUSIONS: Although
      technically more challenging, pouch excision, rather than pouch left in situ, is
      the preferable option for patients who develop pouch failure and are not
      candidates for restoration of intestinal continuity. Because pouch left in situ
      was not associated with neoplasia, this option is a reasonable intermediate or
      long-term alternative when pouch excision is not feasible or advisable.

PMID- 22156862
TI  - Sigmoidectomy syndrome? Patients' perspectives on the functional outcomes
      following surgery for diverticulitis.
AB  - BACKGROUND: Bowel function following surgery for diverticulitis has not
      previously been systematically described. OBJECTIVE: This study aimed to document
      the frequency, severity, and predictors of suboptimal bowel function in patients
      who have undergone sigmoid colectomy for diverticulitis. DESIGN: This study is a
      retrospective analysis. SETTING: This study was conducted at a large, academic
      medical center. PATIENTS: Three hundred twenty-five patients who underwent
      laparoscopic or open sigmoid colectomy with restoration of intestinal continuity
      for diverticulitis were included in the study population. Of these, 249 patients
      (76.6%) returned a 70-question survey incorporating the Fecal Incontinence
      Severity Index, the Fecal Incontinence Quality of Life Scale, and the Memorial
      Bowel Function Instrument. MAIN OUTCOME MEASURES: Survey responders and
      nonresponders were compared with the use of chi and t tests. Responders with
      suboptimal bowel function (fecal incontinence, urgency and/or incomplete
      emptying) were then compared with those with good outcomes by the use of logistic
      regression analysis to determine the predictors of poor function. RESULTS: Of the
      responders, 24.8% reported clinically relevant fecal incontinence (Fecal
      Incontinence Severity Index >= 24), 19.6% reported fecal urgency (Memorial Bowel
      Function Instrument Urgency Subscale >= 4), and 20.8% reported incomplete
      emptying (Memorial Bowel Function Instrument Emptying Subscale >= 4). On logistic
      regression analysis, fecal incontinence was predicted by female sex (OR = 2.3, p
      = 0.008) and the presence of a preoperative abscess (OR = 1.4, p < 0.05). Fecal
      urgency was associated with female sex (OR = 1.3, p < 0.05) and a diverting
      ileostomy (OR = 2.1, p < 0.001). Incomplete emptying was associated with female
      sex (OR = 1.4, p < 0.05) and postoperative sepsis (OR = 1.9, p < 0.05).
      LIMITATIONS: This study was limited by the fact that we did not use a
      nondiverticulitis control group and we had limited preoperative data on the
      history of bowel impairment symptoms. CONCLUSION: One-fifth of patients reported
      fecal urgency, fecal incontinence, or incomplete emptying after surgery for
      diverticulitis. Despite the limitations of our study, these results are
      concerning and should be investigated further prospectively.

PMID- 22156863
TI  - Fecal incontinence in men:  coexistent constipation and impact of rectal
      hyposensitivity.
AB  - BACKGROUND: The pathophysiology of fecal incontinence in men is poorly
      established. OBJECTIVE: The aim of this study was to assess the coexistence of
      constipation and determine the impact of rectal sensorimotor dysfunction in males
      with fecal incontinence. SETTING: This study was conducted at a tertiary referral
      center. PATIENTS: Included were adult male patients referred for the
      investigation of fecal incontinence over a 5-year period who underwent full
      anorectal physiology testing and completed a standardized symptom questionnaire.
      INTERVENTION: Standardized symptom questionnaires were fully completed, and
      anorectal physiologic test results (including evacuation proctography) were
      evaluated. MAIN OUTCOME MEASURES: : The primary outcomes measured were the
      frequency of symptoms of associated constipation, the association of blunted
      rectal sensation (rectal hyposensitivity) with symptoms, and other physiologic
      measures. RESULTS: One hundred sixty patients met the inclusion criteria, and 47%
      of these patients described concurrent constipation. Fifty-four patients (34%)
      had sphincter dysfunction on manometry, only 19 of whom had structural
      abnormalities on ultrasound. Overall, 28 patients (18%) had rectal sensory
      dysfunction, 26 (93%) of whom had rectal hyposensitivity. Patients with rectal
      hyposensitivity were more likely to subjectively report constipation (77%) in
      comparison with patients with normal rectal sensation (44%; p = 0.001), allied
      with decreased bowel frequency (19% vs 2%; p = 0.003) and a sense of difficulty
      evacuating stool (27% vs 8%; p = 0.008). Cleveland Clinic constipation scores
      were higher in patients with rectal hyposensitivity (median score, 13
      (interquartile range: 8-17) vs normosensate, 9 (5-13); p = 0.004). On
      proctography, a higher proportion of patients with rectal hyposensitivity had
      protracted defecation (>180 s; 35% vs 10%; p = 0.024) and incomplete rectal
      evacuation (<55% of barium neostool expelled, 50% vs 20%; p = 0.02). LIMITATIONS:
      : This study was limited by the retrospective analysis of prospectively collected
      data. CONCLUSIONS: Only one-third of incontinent men had sphincteric dysfunction.
      Other pathophysiologies must therefore be considered. Nearly half of patients
      reported concurrent constipation, and one-sixth had rectal hyposensitivity, which
      was associated with higher frequencies of both symptomatic and objective measures
      of rectal evacuatory dysfunction. In the majority of adult males, fecal
      incontinence may represent a secondary phenomenon.

PMID- 22156864
TI  - Medium-term outcome of sacral nerve modulation for constipation.
AB  - BACKGROUND: Sacral nerve modulation has been reported as a minimally invasive and
      effective treatment for constipation refractory to conservative treatment.
      OBJECTIVE: This study aimed to evaluate the efficacy and sustainability of sacral
      nerve modulation for constipation in the medium term (up to 6 years) and to
      investigate potential predictors of treatment success. DESIGN: We performed a
      retrospective review of prospectively collected data. SETTINGS: The study was
      performed at 2 tertiary-care centers in Europe with expertise in pelvic floor
      disorders and sacral nerve modulation. PATIENTS: Patients were eligible if they
      had had symptoms of constipation persisting for at least 1 year, if conservative
      treatment (dietary modification, laxatives and biofeedback therapy) had failed,
      and if predefined excluded conditions were not present. INTERVENTION: The first
      phase of the treatment process was percutaneous nerve evaluation. If this was
      successful, patients underwent sacral nerve modulation therapy with an implanted
      device (tined-lead and implantable pulse generator). MAIN OUTCOME MEASURE: Follow
      up was performed at 1, 3, 6, and 12 months, and yearly thereafter. Outcome was
      assessed with the Wexner constipation score. RESULTS: A total of 117 patients (13
      men, 104 women) with a mean age of 45.6 (SD, 13.0) years underwent percutaneous
      nerve evaluation. Of these, 68 patients (58%) had successful percutaneous nerve
      evaluation and underwent implantation of a device. The mean Wexner score was 17.0
      (SD, 3.8) at baseline and 10.2 (SD 5.3) after percutaneous nerve evaluation (p <
      .001); the improvement was maintained throughout the follow-up period, although
      the number of patients continuing with sacral nerve modulation at the latest
      follow-up (median, 37 months; range, 4-92) was only 61 (52% of all patients who
      underwent percutaneous nerve evaluation). The sole predictive factor of outcome
      of percutaneous nerve evaluation was age: younger patients were more likely than
      older patients to have a successful percutaneous nerve evaluation phase.
      LIMITATIONS: The study was limited by a lack of consistent outcome measures.
      CONCLUSIONS: : Despite improvement in Wexner scores, at the latest follow-up
      sacral nerve modulation was only being used by slightly more than 50% of the
      patients who started the first phase of treatment. Further studies are needed to
      reassess the efficacy and sustainability of sacral nerve modulation.

PMID- 22156865
TI  - Combined ischemic and neuropathic insult to the anal canal in an animal model of
      obstetric-related trauma.
AB  - BACKGROUND: Childbirth, in particular, when it involves instrumental vaginal
      delivery, can result in direct trauma to the external anal sphincter muscle. In
      addition, a global injury to the pelvic floor, including neurovascular injury to
      the anal sphincter complex, may occur. OBJECTIVE: The aims of this study were to
      determine whether sensory drive from the anal canal and oxygenation of the
      external anal sphincter were compromised during simulated labor in a validated
      animal model of obstetric trauma. DESIGN: Fifteen female Wister rats were
      operated on. Group 1 (n = 5) underwent pelvic balloon compression for 1 hour to
      simulate increased pelvic pressure during childbirth. Somatosensory cortical
      potentials, evoked by electrically stimulating the anal canal, were tracked. In
      group 2 (sham), the balloons were not inflated. In group 3, tissue PO2 values of
      the external anal sphincter and femoral arterial blood flow were measured
      simultaneously during the period of balloon inflation. RESULTS: The peak
      amplitude of cortical evoked potentials was reduced (from 11.8 +/- 1.5 MUV to 3.1
      +/- 1.1 MUV) during pelvic compression (p = 0.002, ANOVA). During this period,
      arterial blood flow to the hindlimb and the external anal sphincter tissue PO2
      decreased by 20% (p < 0.001) and 60% (p < 0.001). CONCLUSION: Pelvic compression
      that mimics obstetric trauma is associated with diminished anocortical drive.
      This neural insult may be compounded by concomitant ischemia of the external anal
      sphincter.

PMID- 22156866
TI  - Improved short-term outcomes of laparoscopic versus open resection for colon and
      rectal cancer in an area health service: a multicenter study.
AB  - BACKGROUND: Evidence demonstrates short-term benefits of laparoscopic surgery for
      colon cancer. The situation for rectal cancer is less clear. OBJECTIVES: This
      review assessed the use and short-term outcomes of elective open and laparoscopic
      colon and rectal cancer resections within an area health service. DESIGN: This
      was a multicenter, retrospective review of a prospective database. SETTINGS: All
      elective colon and rectal cancer resections in the western zone of Sydney South
      West Area Health Service from 2001 until 2008 were included. PATIENTS: Included
      were 1721 patients who underwent either a laparoscopic colon (n = 434) or rectal
      (n = 157) resection or an open colon (n = 742) or rectal (n = 388) resection.
      MAIN OUTCOME MEASURES: : Outcome measures included operating time, blood loss,
      adequacy of resection, conversion rate, intensive care unit admission, length of
      stay, and 26 acute postoperative complications. RESULTS: Patients were matched
      for age, sex, ASA, BMI, and tumor stage. Laparoscopic surgery increased in
      frequency. Fewer patients experienced a complication in both the laparoscopic
      colon (28.8 vs 54.4%; p < 0.0001) and rectal (41.4 vs 60.3%; p < 0.0001) group
      irrespective of age. Laparoscopic operating time for colon and rectal cancer was
      24.1 minutes (p < 0.0001) and 25.8 minutes (p < 0.0001) longer, with a low
      conversion-to-open rate (6.5% and 8.3%; p = 0.44). Laparoscopic surgery resulted
      in fewer transfusions (0.4 vs 0.7 units; p = 0.0028) and length of stay (7 vs 10
      days; p = 0.0011) for colon cancers, and reduced intraoperative hemoglobin drop
      (20.5 vs 24.8; p = 0.029) and intensive care unit admissions (26.8 vs 36.3%; p =
      0.032) for rectal cancers. LIMITATIONS: : This was a nonrandomized study with
      rectal cancers more often resected with the open technique (71.2 vs 28.8%; p <
      0.001). CONCLUSIONS: Within an area health service, elective laparoscopic
      resection for colon and rectal cancer had improved short-term outcomes in
      comparison with open surgery.

PMID- 22156867
TI  - Factors associated with oncologic outcomes after abdominoperineal resection
      compared with restorative resection for low rectal cancer:  patient- and tumor
      related or technical factors only?
AB  - BACKGROUND: Previous reports suggest that patients with rectal cancer undergoing
      abdominoperineal resection have worse oncologic outcomes in comparison with those
      undergoing restorative rectal resection. OBJECTIVE: This study aimed to assess
      factors influencing oncologic outcomes for patients undergoing surgery for rectal
      cancer. DESIGN: This study is a retrospective review of prospectively gathered
      data. SETTING: Data were gathered from a prospective cancer database. PATIENTS:
      Patients were included who underwent radical resection for mid and lower third
      rectal cancer (1991-2006). MAIN OUTCOME MEASURES: The primary outcomes measured
      were the impact of various factors on perioperative outcomes, local recurrence,
      and disease-free survival for patients undergoing abdominoperineal resection.
      RESULTS: Four hundred thirteen (29%) patients underwent abdominoperineal
      resection and 993 (71%) underwent restorative resection for rectal cancer.
      Patients with abdominoperineal resection were older (p < 0.0001), had a higher
      mean ASA score (p < 0.001), worse tumor differentiation (p < 0.001), and higher
      tumor stage (p = 0.0001). Although overall morbidity was lower in the
      abdominoperineal resection group (p = 0.001), the length of stay was greater (p <
      0.001). After a similar period of follow-up (5.2 +/- 3.9 vs 5.3 +/- 3.4 y, p =
      0.58), local recurrence (7% vs 3%, p = 0.02) was higher after abdominoperineal
      resection, but overall survival (56% vs 71%, p < 0.001) and disease-free survival
      (54% vs 70%, p < 0.001) were lower. On multivariate analysis, higher stage, poor
      tumor differentiation, involved margins, and older age were associated with worse
      survival, whereas higher stage, poor tumor differentiation, and abdominoperineal
      resection were associated with greater recurrence. These worse oncologic outcomes
      persisted even when the groups were stratified based on the location of the
      cancer in mid or distal rectum and for patients with a clear circumferential
      margin. LIMITATION: This study was limited by its retrospective nature.
      CONCLUSION: Technical factors alone are unlikely to be responsible for the worse
      outcomes after abdominoperineal resection in comparison with restorative
      resection. A combination of patient- and tumor-related factors that may have
      indicated the choice of the procedure also probably contribute to the worse
      outcomes. Because patients undergoing abdominoperineal resection represent a high
      risk for poor outcomes, management strategies need to consider all these factors
      during treatment.

PMID- 22156868
TI  - Accuracy of endorectal ultrasound for measurement of the closest predicted radial
      mesorectal margin for rectal cancer.
AB  - BACKGROUND: At present, pelvic phased array-coil MR is used as the validated
      imaging modality for measurement of the closest predicted radial mesorectal
      margin for rectal cancer. Endorectal ultrasound is also used to assess the
      clinical stage of the cancer that will determine the recommendation for
      neoadjuvant chemoradiation, but it has not been used to assess the closest
      predicted radial margin. OBJECTIVE: We propose to assess endorectal ultrasound
      identification of mesorectal margins and the measurement of the closest predicted
      radial tumor-mesorectal margin. PATIENTS AND METHODS: Patients included were
      those having MRI and endorectal ultrasound for evaluation of primary rectal
      cancer in 2010 at a tertiary cancer referral colorectal clinic. Clinical data,
      MRI, and endorectal ultrasound images were assessed. Two independent
      retrospective measurements of mesorectal dimensions were correlated to evaluate
      the reproducibility of identifying mesorectal margins. MRI and endorectal
      ultrasound images were compared for independent measurements of mesorectal
      dimensions and of the closest predicted radial mesorectal margin. MRI and
      endorectal ultrasound determination of margin involvement were assessed for
      agreement. RESULTS: Fifty-two patients were studied with an average rectal cancer
      distance to the anal verge of 6.8 cm. Interobserver correlation coefficients of
      endorectal ultrasound mesorectal dimensions ranged from 0.47 to 0.53 (p < 0.01).
      MR and endorectal ultrasound measurements of the closest predicted radial
      mesorectal margin were correlated r = 0.56 (p < 0.0001). MR and endorectal
      ultrasound determination of margin involvement agreed in 81% of cases.
      CONCLUSION: Endorectal ultrasound has substantial agreement with MR to measure
      the closest predicted radial tumor-mesorectal margin. Correlations between
      observers and modalities for identification of mesorectal dimensions are modest.
      Further assessment is indicated to confirm endorectal ultrasound mesorectal
      measurements in a larger sample and to understand the advantages and
      disadvantages relative to MR.

PMID- 22156869
TI  - Early versus late surgery in patients with intestinal Behcet disease.
AB  - BACKGROUND: To date, no studies have been conducted to evaluate the potential
      benefits of early surgery in patients with intestinal Behcet disease. OBJECTIVE:
      We investigated the long-term clinical outcomes in patients with intestinal
      Behcet disease first diagnosed at surgery ("early surgery") compared with those
      requiring surgical resection during the course of the disease ("late surgery").
      DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted
      at a single tertiary academic medical center. PATIENTS: We reviewed the medical
      records of 272 consecutive patients with intestinal Behcet disease between March
      1986 and August 2010. MAIN OUTCOME MEASURES: The cumulative probabilities of
      clinical recurrence and reoperation after operation were the main outcomes
      measures. RESULTS: Forty of 272 patients were first diagnosed with intestinal
      Behcet disease at surgery (early surgery); the remaining 232 were diagnosed
      clinically, with 62 undergoing surgery during their follow-up after clinical
      diagnosis (late surgery). The cumulative probabilities of postoperative clinical
      recurrence and reoperation were significantly lower in the early-surgery group
      than in the late-surgery group (p = 0.045 and p = 0.003). In multivariate
      analysis, early surgery was the only independent factor significantly associated
      with a reduced probability of reoperation (HR 0.26; 95% CI 0.10-0.71; p = 0.008).
      However, when we analyzed only the patients who underwent surgery because of
      chronic symptoms, early surgery was not associated with lower cumulative clinical
      recurrence and reoperation rates (p = 0.896 and p = 0.492). LIMITATIONS: We
      analyzed the clinical characteristics retrospectively, and the number of patients
      was insufficient to reach a decisive conclusion. CONCLUSIONS: : According to the
      current study, the patients with intestinal Behcet disease undergoing early
      surgery showed better prognoses in comparison with those undergoing late surgery.
      Early surgery may represent a valid approach in the initial management of the
      patients with intestinal Behcet disease, at least in the subset of the patients
      with acute symptoms.

PMID- 22156870
TI  - One-stage segmental colectomy and primary anastomosis after intraoperative
      colonic irrigation and total colonoscopy for patients with obstruction due to
      left-sided colorectal cancer.
AB  - BACKGROUND: Intraoperative colonic irrigation and intraoperative on-table
      colonoscopy may be useful for a more accurate diagnosis of colorectal cancer
      before colectomy in patients with obstructive left-sided colorectal cancer, but
      the clinical benefit of this technique has not been investigated in large-scale
      studies. OBJECTIVE: The aim of this study was to evaluate the usefulness of
      intraoperative colonic irrigation with a Y-shaped irrigation device and
      intraoperative colonoscopy in the management of obstructive colorectal cancer in
      patients undergoing elective surgery. DESIGN AND SETTING: This was a
      retrospective cohort study of patients undergoing surgical treatment at a single
      tertiary care institution in Japan. PATIENTS AND INTERVENTION: Among 715
      consecutive patients with left-sided colorectal cancer, 101 patients (14.1%) with
      obstructing tumor received intraoperative colonic irrigation and intraoperative
      colonoscopy before colectomy and primary anastomosis, and 614 patients with
      nonobstructive colorectal cancer underwent preoperative colonoscopy with
      mechanical bowel preparation. MAIN OUTCOME MEASURES: Detection rates of proximal
      synchronous lesions, occurrence of postoperative complications, and changes in
      the surgical procedure prompted by the results of the intraoperative colonoscopy
      were evaluated. RESULTS: Intraoperative colonoscopy detected synchronous
      adenomatous polyps in 27 patients (26.8%), carcinoma in 4 patients (4%), and
      obstructive colitis in 2 patients (2%). Findings of the intraoperative
      colonoscopy prompted changes in surgical procedure in 9 patients (8.9%). The
      overall morbidity in the intraoperative group was 17%, with anastomotic leakages
      in 3 patients, wound infection in 5, and postoperative ileus in 3 patients. The
      risk of these complications was not increased in patients with intraoperative
      colonoscopy with intraoperative colonic irrigation compared with those receiving
      preoperative colonoscopy with mechanical bowel preparation. The operation time
      was 28 minutes longer in the intraoperative than in the preoperative group, but
      neither the time to start of oral intake nor the length of postoperative hospital
      stay was significantly different between the 2 groups. LIMITATIONS: The study is
      limited by its retrospective nature. CONCLUSIONS: : In patients with obstructive
      colorectal cancer, intraoperative colonic irrigation with intraoperative
      colonoscopy is a useful strategy for detecting synchronous lesions located
      proximally to the obstructing tumor, without increasing patient morbidity.

PMID- 22156871
TI  - Inflammatory bowel disease complicated by primary sclerosing cholangitis and
      cirrhosis:  is restorative proctocolectomy safe?
AB  - BACKGROUND: The pattern and severity of postoperative complications after
      colectomy and total proctocolectomy with ileoanal pouch for patients with IBD
      with liver cirrhosis from primary sclerosing cholangitis have not been well
      characterized. OBJECTIVE: This study aimed to evaluate the immediate and long
      term outcomes for patients with cirrhosis from primary sclerosing cholangitis
      undergoing colectomy for IBD. DESIGN: This is a retrospective study. SETTING:
      This study was conducted at Cleveland Clinic, a tertiary medical center.
      PATIENTS: From 1989 to 2009, 23 patients (22 ulcerative colitis and 1 Crohn's
      disease) who underwent colectomy were included. RESULTS: The mean duration of
      primary sclerosing cholangitis before surgery was 6.8 +/- 4.9 years, and the mean
      duration of IBD was 18 +/- 10.7 years. All patients had cirrhosis; the mean Model
      for Endstage Liver Disease score was 9.3 +/- 1.6, and most patients were Child
      Pugh class A or early B. Eight patients were on the orthotopic liver
      transplantation list. Indications for colectomy were dysplasia (n = 13), failure
      or complications of medical therapy (n = 7), cancer (n = 2), and colonic
      perforation at colonoscopy (n = 1). Nineteen patients (82.6%) developed
      postoperative complications including bleeding (43.5%), ileus (17.4%), wound
      infection (8.7%), worsening liver function (34.8%), pelvic abscess (13%), and
      deep vein thrombosis (8.7%). Two patients, both after total proctocolectomy/IPAA,
      died of septic shock after pelvic abscess in the postoperative period. Two
      patients underwent transjugular intrahepatic portosystemic shunt procedure before
      total proctocolectomy/IPAA; none developed pelvic abscess or mortality. There
      were no differences in mortality or morbidity between patients who underwent an
      ileoanal pouch procedure or colectomy with ileostomy. CONCLUSIONS: Colectomy in
      patients with IBD complicated with cirrhotic primary sclerosing cholangitis is
      associated with a high early postoperative morbidity rate. Due consideration
      needs to be given to strategies to reduce pelvic sepsis, especially after
      ileoanal pouch, because this is associated with mortality.

PMID- 22156872
TI  - Assessment of the quality of patient-orientated Internet information on surgery
      for diverticular disease.
AB  - BACKGROUND: The Internet is a vast resource available for patients to obtain
      health information. OBJECTIVE: This study examines the quality of Web sites that
      provide information on diverticular disease, treatment options, and surgery.
      DESIGN: Two search engines (Google and Yahoo) and the search terms "surgery and
      diverticular disease" and "surgery and diverticulitis" were used. The first 50
      sites of each search were assessed. Sites that fulfilled the inclusion criteria
      were evaluated for content and scored by using the DISCERN instrument, which
      evaluates the quality of health information on treatment choices. RESULTS: Two
      hundred sites were examined, of which 60 (30%) provided patient-orientated
      information. 50 sites (25%) were duplicated, 7 (3.5%) were links, 10 (5%) were
      advertisements, 14 (7%) were resources for clinicians, 9 (4.5%) were message
      forums, 27 (13.5%) were articles, and 15 (7.5%) were dead links. Of the 60 Web
      sites that provided patient information, only 10 (16.7%) had been updated within
      the past 2 years. Seventeen (28.3%) sites were affiliated with hospitals and
      clinics, but another 17 (28.3%) sites were associated with private companies with
      commercial interests. Although most Web sites contained information on symptoms,
      complications, investigations, and treatment options of diverticular disease, 20
      (33.3%) did not describe any of the risks of surgery, and 45 (75%) did not
      provide information on the timescale of recovery postoperatively. Eighteen sites
      did not provide balanced information on treatment options; of these, 7 were
      biased toward medical treatment and 6 focused on laparoscopic surgery. Overall,
      only 22 (36.7%) were identified as being "good" or "excellent" with the use of
      the DISCERN criteria. CONCLUSIONS: The quality of patient information on surgery
      for diverticular disease is highly variable, and Web sites that are sponsored by
      private companies may be biased in discussing treatment options. There is
      potential for the Internet to provide valuable information, and clinicians should
      guide patients to access high-quality Web sites.

PMID- 22156873
TI  - Perineal hernia repair after abdominoperineal rectal excision.
AB  - BACKGROUND: A perineal hernia can severely disable everyday activities. Its
      repair is a surgical challenge, and guidance by the literature is limited. The
      series described so far are small or encompass a long period in which even
      nonmesh techniques were used. OBJECTIVE: The aim of this study was to review
      recent results of a perineal mesh-based repair. PATIENTS: Medical charts of
      patients with a symptomatic perineal hernia after abdominoperineal resection due
      to rectal cancer were reviewed. MAIN OUTCOME MEASURES: Data included patients'
      characteristics, operative details, recurrence, and complications. RESULTS: In
      total, 29 patients underwent repair of a symptomatic perineal hernia after an
      abdominoperineal resection due to rectal cancer. The majority was male (66%), and
      the median age was 59 years (range, 41-83). All patients received neoadjuvant
      treatment.From 2003 until 2006, polytetrafluoroethylene or Vypro mesh and Prolene
      2.0 sutures were used for perineal hernia repair. All 8 repairs failed; repeated
      repair using various methods was successful in 63%. After 2006, the surgical
      technique was changed into a high-tension repair with the use of a nonabsorbable
      mesh. This technique was successful for 20 of 21 patients (95%). Complications
      encountered in the entire group of 29 patients were urinary retention (n = 2),
      wound infection, seroma, and fistula (n = 1 each). LIMITATIONS: Even though this
      is the largest group described in the literature, the results are limited because
      of the small number of patients. CONCLUSION: Repair of perineal hernia remains
      challenging and only a few reports offer advice on how to manage this unusual
      problem. However, superior results have been shown with the new mesh-based
      technique through perineal approach with only 5% recurrence.

PMID- 22156874
TI  - Epigenetic regulation and colorectal cancer.
AB  - Epigenetic silencing of genes is now recognized to be an important mechanism for
      inactivation of tumor suppressor genes in carcinogenesis. Because the role of
      genetic alterations in colorectal carcinogenesis has been well studied,
      colorectal cancer also offers an excellent model for elucidation of epigenetic
      mechanisms involved in carcinogenesis. DNA methylation and histone modification
      are involved in a complex network to maintain gene silencing and cause
      carcinogenesis. DNA methylation of cancer-related gene promoters generally begins
      early in the process of tumorigenesis, affecting various types of colorectal
      cancer to differing degrees. These advances in the understanding of the biology
      of tumorigenesis can be expected to provide distinct biomarkers that will aid
      future diagnosis, risk assessment, and treatment methods for patients with
      colorectal cancer.

PMID- 22156875
TI  - Should we care about the internal anal sphincter?
AB  - The internal anal sphincter is currently regarded as a significant contributor to
      continence function. Four physiological and morphological aspects of the internal
      anal sphincter are presented as part of the current evidence base for its
      preservation in anal surgery. 1) The incidence of continence disturbance
      following deliberate internal anal sphincterotomy is underestimated, although
      there is presently no prospective imaging or physiologic data supporting the
      selective use of sphincter-sparing surgical alternatives. 2) Given that the
      resting pressure is a measure of internal anal sphincter function, its
      physiologic representation (the rectoanal inhibitory reflex) shows inherent
      differences between incontinent and normal cohorts which suggest that internal
      anal sphincter properties act as a continence defense mechanism. 3) Anatomical
      differences in distal external anal sphincter overlap at the point of internal
      anal sphincter termination may preclude internal anal sphincter division in some
      patients where the distal anal canal will be unsupported following deliberate
      internal anal sphincterotomy. 4) internal anal sphincter-preservation techniques
      in fistula surgery may potentially safeguard postoperative function. Prospective,
      randomized trials using preoperative sphincter imaging and physiologic parameters
      of the rectoanal inhibitory reflex are required to shape surgical decision making
      in minor anorectal surgery in an effort to define whether alternatives to
      internal anal sphincter division lead to better functional outcomes.

PMID- 22156876
TI  - Full-thickness skin graft anoplasty:  novel procedure.
AB  - We describe a novel technique to treat anal stenosis by reconstructing the anal
      canal by the use of a full-thickness skin graft from the abdominal wall. This
      treatment was successfully applied in our institution and showed positive
      results.

PMID- 22156879
TI  - Robotic vs laparoscopic resection of rectal cancer: short-term outcomes of a case
      control study.

PMID- 22156881
TI  - The evolving diagnosis and treatment of uncomplicated diverticulitis (from the
      perspective of emergency physicians).

PMID- 22156884
TI  - A Meta-analysis of Outcomes Using Acellular Dermal Matrix in Breast and Abdominal
      Wall Reconstructions: Event Rates and Risk Factors Predictive of Complications.
AB  - BACKGROUND: The use of acellular dermal matrix (ADM) has gained acceptance in
      breast and abdominal wall reconstructions. Despite its extensive use, there is
      currently a wide variation of reported outcomes in the literature. This study
      definitively elucidates the outcome rates associated with ADM use in breast and
      abdominal wall surgeries and identifies risk factors predisposing to the
      development of complications. METHODS: A literature search was conducted using
      the Medline database (PubMed, US National Library of Medicine) and the Cochrane
      Library. A total of 464 articles were identified, of which 53 were eligible for
      meta-analysis. The endpoints of interest were the incidences of seroma,
      cellulitis, infection, wound dehiscence, implant failure, and hernia. The effects
      of various risk factors such as smoking, radiation, chemotherapy, and diabetes on
      the development of complications were also evaluated. RESULTS: A majority of the
      studies were retrospective (68.6%) with a mean follow-up of 16.8 months (SD +/-
      10.1 months) in the breast group and 14.2 months (SD +/- 7.8 months) in the
      abdominal wall reconstructive group. The overall risks and complications were as
      follows: cellulitis, 5.1%; implant failure, 5.9%; seroma formation, 8%; wound
      dehiscence, 8.1%; wound infection, 16.1%; hernia, 27.6%; and abdominal bulging,
      28.1%. Complication rates were further stratified separately for the breast and
      abdominal cohorts, and the data were reported. This provides additional
      information on the associated abdominal wall morbidity in patients undergoing
      autologous breast reconstruction in which mesh reinforcement was considered as
      closure of the abdominal wall donor site. Radiation resulted in a significant
      increase in the rates of cellulitis (P = 0.021), and chemotherapy was associated
      with a higher incidence of seroma (P = 0.014). CONCLUSION: This study evaluates
      the overall complication rates associated with ADM use by conducting a meta
      analysis of published data. This will offer physicians a single comprehensive
      source of information during informed consent discussions as well as an awareness
      of the risk factors predictive of complications.

PMID- 22156885
TI  - Relation between reduction mammaplasty and pulmonary functions.
AB  - The hypothesis that weight on the chest may diminish the compliance of the chest
      wall and affect chest wall dynamics guided this research. Few previous studies
      investigated the possibility of increasing chest compliance and pulmonary
      function after reduction mammaplasty. The meager results available were
      contradictory. The aim of this study was to determine the relation between
      reduction mammaplasty and pulmonary function. Thirty-three adult female patients
      who presented for reduction mammaplasty were included in the study. Paired t test
      showed nonsignificant change in pulmonary functions after reduction mammaplasty.
      Pearson method of statistical analysis revealed a significant positive
      correlation between the total weight of breast tissue removed and pulmonary
      function, and a negative correlation between the total postoperative breast
      volume and the pulmonary function. The study concluded that the more the breast
      tissue weight removed and the less the postoperative total breast volume, the
      better the postoperative pulmonary function.

PMID- 22156886
TI  - Microsurgical training with fresh chicken legs.
AB  - PURPOSE: With the increasing use of microsurgical techniques in clinical work,
      regular laboratory training in these techniques has become essential. Several
      specialized materials have been used for this purpose. We investigated whether
      effective training could be provided with greater convenience and less expense
      using fresh chicken thighs. Also, we present the histologic characteristics of
      chicken femoral neurovascular structures. METHODS: The femoral neurovascular
      bundles of fresh chicken thighs were dissected. Microanastomosis of vessels and
      nerves were performed with the aid of a microscope. Tissue from the midthigh of 8
      chickens was examined histologically. RESULTS: It was found to reduce the time
      taken to perform anastomoses using the chicken thigh model with statistically
      significance. The mean diameters (+/- standard deviations) of the arteries,
      veins, and nerves were 2.04 +/- 0.17 mm, 1.45 +/- 0.06 mm, and 1.24 +/- 0.08 mm,
      respectively. The observed tunica adventitia to media ratio was 1:1 and multiple
      nerve fascicles were wrapped in a single epineurium. Microsurgery training with
      this material provides several advantages: ready availability, minimal expense,
      no scheduling or location limitations, neurorrhaphy training, no need for special
      facilities for animal care or anesthesia, and no need for the trimming of
      adventitia. CONCLUSION: The femoral neurovascular bundles of chicken are an
      appropriate and effective model for teaching and practicing microsurgery.

PMID- 22156887
TI  - Indications and outcomes following complex abdominal reconstruction with
      component separation combined with porcine acellular dermal matrix reinforcement.
AB  - PURPOSE: Component separation (CS) is an effective technique for complex
      abdominal wall reconstruction (AWR). Reinforcement of the repair with mesh can
      add durability. The purpose of this study was to evaluate the indications and
      outcomes following CS combined with a porcine acellular dermal matrix (PADM) for
      reinforcement. METHODS: A retrospective review of all patients who underwent
      complex AWR at the authors' institution was completed between 2007 and 2010.
      Patients with complex hernias who underwent CS in conjunction with PADM as an
      underlay were included. The PADM used in this cohort was Strattice (LifeCell
      Corporation, Branchburg, NJ). Patient demographics, indications, perioperative
      details, postoperative care, and long-term outcomes were reviewed. RESULTS: A
      total of 78 patients were identified as having PADM implanted for AWR. Of this
      cohort, 41 patients met the criteria as having a CS to achieve midline closure,
      with the PADM placed as reinforcement in an underlay manner. These patients were
      classified as grade II (33; 80.5%), grade III (4; 9.8%), and grade IV (4; 9.8%).
      Average patient age was 57.6 years (range, 33-80), and average body mass index
      (BMI) was 35.8 kg/m2 (range, 21.6-52.1). Patient comorbidities included coronary
      artery disease (19; 46.3%), diabetes mellitus (14; 34.2%), chronic obstructive
      pulmonary disease (COPD) (6; 14.6%), and chronic steroid use (2; 4.9%). Previous
      mesh infection occurred in 9 (28.1%). The mean defect diameter was found to be
      14.3 cm. Perforator preservation of the subcutaneous flaps was performed in 34
      (82.9%) patients. A concomitant panniculectomy was performed in 9 (22%) patients.
      A staged approach was used in 3 (7.3%) patients. The overall complication rate
      was 24.4%. Strattice exposure occurred in 5 (12.2%) patients. All patients went
      on to heal wounds without explantation.No hernia recurrences or symptomatic
      bulges were observed in the follow-up period of 474 days (range, 194-1017 days).
      No significant predictors of complications were identified. CONCLUSIONS:
      Strattice is an effective adjunct to AWR when used as reinforcement during CS for
      a wide variety of indications. Complication rates remain low in complex patients.
      In addition, Strattice appears to add durability to midline reconstructions with
      no recurrences during the follow-up period.

PMID- 22156888
TI  - The tropical diabetic hand syndrome: a surgical perspective.
AB  - Tropical diabetic hand syndrome (TDHS) is an aggressive type of hand sepsis that
      results in significant morbidity and mortality among patients with diabetes in
      the tropics. This study set out to establish a protocol for the holistic
      management of TDHS to improve digit/hand salvage and function at AIC Kijabe
      Hospital. This prospective study examined the following demographics of patients
      presenting to the authors institution between October 2009 and September 2010
      with TDHS: their sex, age, comorbidities, length of in-hospital stay, surgical
      and medical treatment, total cost of treatment, and immediate postdischarge
      outcomes. A total of 10 patients (3 men and 7 women) were presented with TDHS
      during the study period. Surgical procedures included a thorough debridement of
      the hand at initial presentation, followed by procedures aimed at preserving
      length and hand function, with digit or hand amputation when there was no
      possibility of salvage. Three hands were salvaged, without the need for an
      amputation; 2 of these, however, developed severe stiffness with resultant poor
      function. Fifty percent of the patients developed considerable disability; 3 of
      these patients had disabilities of the arm, shoulder, and hand, (DASH) scores of
      >90 at 6 months after treatment. TDHS appears to be more aggressive in some
      patients than in others; a multidisciplinary approach, with early involvement of
      the surgical team, and a radical surgical debridement are essential to improved
      outcomes. Although the goal of medical treatment (ie, glycemic control) is simple
      and easily achieved, surgical goals (salvage of limb or life, preservation of
      hand function) are more complex, costly, and difficult to achieve. Educating
      health care workers, diabetic patients, and their relatives on hand care is an
      important preventive measure. Diligence in taking antidiabetic medicine, early
      presentation, and appropriate care of TDHS are required for meaningful
      improvement in outcomes of patients with diabetes who develop hand sepsis in the
      tropics.

PMID- 22156889
TI  - Intraoperative esophageal Doppler hemodynamic monitoring in free perforator flap
      surgery.
AB  - Goal-directed fluid therapy optimizes cardiac output and flap perfusion during
      anesthesia. Intraoperative esophageal Doppler (ED) monitoring has been reported
      as more accurate and reliable, demonstrating improved surgical outcomes compared
      with central venous pressure and arterial catheter monitoring. A prospective
      study of patients undergoing free perforator (deep inferior epigastric artery
      perforator/anterolateral thigh) flap surgery with intraoperative ED monitoring
      (51 patients) or central venous pressure monitoring (53 patients) was undertaken.
      Fluid input included crystalloids, colloids, or blood products. Fluid output
      included urine, blood, or suctioned fluid. Postoperative fluid balance was
      calculated as fluid input - output. Fluid input between groups was not different.
      Fluid output was greater in the ED group (P = 0.008). The ED group showed less
      fluid balance (P = 0.023), less anesthetic time (P = 0.001), less hospital stay
      (mean 1.9 days; P = 0.147), less monitoring and flap complications (P = 0.062).
      ED monitoring demonstrated no monitoring complications, provides a favorable
      postoperative fluid balance, and may reduce flap complications and hospital stay.

PMID- 22156890
TI  - Use of the osteomuscular dorsal scapular flap in the reconstruction of mandibular
      defects.
AB  - The gold standard for mandibular defect reconstruction is the fibular free flap.
      Nevertheless, the pedicled osteomuscular dorsal scapular flap as a reconstructive
      tool offers promise for mandibular defect reconstruction and could be the first
      choice in certain circumstances. Its use in resource-limited settings offers an
      excellent solution to otherwise difficult reconstructive problems of the
      mandible. In 8 patients, mandibular defects resulting from the excision of benign
      tumors (6), trauma (1), and chronic osteomyelitis (1) were reconstructed using
      the pedicled osteomuscular dorsal scapular flap; these defects included the
      central segment of the mandible. The pedicled osteomuscular dorsal scapular flap
      is an excellent choice for mandibular reconstruction; it may serve as the primary
      choice in patients with vascular pathology that precludes free tissue transfer,
      as well as in resource-limited environments, as a secondary choice after a failed
      free flap reconstruction.

PMID- 22156891
TI  - National representation in the plastic and reconstructive surgery literature: a
      bibliometric analysis of highly cited journals.
AB  - BACKGROUND: In recent years, significant growth has been observed in the field of
      plastic and reconstructive surgery. However, the national productivity to the
      field of plastic and reconstructive surgery remains unknown. We therefore
      intended to reveal national contributions in the field of plastic and
      reconstructive surgery. METHODS: Articles published in the 6 highly cited
      journals in plastic and reconstructive surgery in 2005-2009 were retrieved from
      the Medline and Web of Science. The number of total articles, the per capita
      numbers, 5-year impact factors (5y-IF), and citations were tabulated to assess
      the contribution of different countries. RESULTS: A total number of 5745 articles
      were published in the 6 journals from 2005 to 2009 worldwide. North America, West
      Europe, and East Asia were the most productive regions. High-income countries
      published 79.72% of the total articles. United States (USA) published most of the
      articles during 2005 to 2009 (2015/5745, 35.07%), followed by United Kingdom,
      Turkey, Japan, and China. Besides, USA also had the highest total 5y-IF
      (5010.76), the highest mean 5y-IF (2.49), and the highest total citations
      (11,788). When normalized to population size, Sweden had the highest number of
      articles per million persons (12.26), followed by Switzerland (8.02) and
      Netherlands (7.77). CONCLUSIONS: USA is the most productive country in the field
      of plastic and reconstructive surgery. When normalized to population size, some
      European countries might be more productive.

PMID- 22156892
TI  - A double-blind, placebo-controlled study on the effect of buprenorphine and
      fentanyl on descending pain modulation: a human experimental study.
AB  - OBJECTIVES: The descending pain inhibitory system is impaired in chronic pain and
      it is important to know how analgesics interact with this system. The aim of this
      human experimental pain, double-blind, randomized, placebo-controlled, 3 way
      cross-over study was to investigate the effect of 2 different opioids on
      descending pain inhibition using conditioning pain modulation (CPM) as a
      screening tool. METHODS: Twenty-two healthy male volunteers were randomized to 72
      hours of treatment with transdermal patches of fentanyl (25 MUg/h), buprenorphine
      (20 MUg/h), or placebo. The CPM was induced by immersing the hand into cold (3.0
      +/- 0.3 degrees C) water and the evoked pain was continuously rated on a visual
      analogue scale (VAS). The test stimulus [pressure pain tolerance threshold
      (PPTol)] was applied to the contra-lateral arm. The CPM test was performed at
      baseline, 24, 48, and 72 hours after application of the patches. RESULTS: The
      opioid treatments did not significantly (F=2.249; P=0.07) modulate the PPTol over
      the treatment period compared with placebo. The CPM-evoked PPTol increases
      (percentage increase from what was obtained at the baseline before patch
      application) were significantly enhanced by buprenorphine (P=0.004) and fentanyl
      (P=0.005) compared with placebo, with no differences between the 2 active drugs.
      Fentanyl significantly attenuated the time to cold water-evoked VAS peak compared
      with placebo (P=0.005), and the same trend was observed for buprenorphine
      (P=0.06). The VAS pain intensity was not affected. DISCUSSION: The opioids
      buprenorphine and fentanyl significantly potentiate the effect of descending pain
      inhibition in healthy volunteers.

PMID- 22156893
TI  - A multi-institutional study analyzing effect of prophylactic medication for
      prevention of opioid-induced gastrointestinal dysfunction.
AB  - OBJECTIVES: The aim of this study was to evaluate the effectiveness of
      prophylactic treatment with laxatives and antiemetics on the incidence of
      gastrointestinal adverse reactions such as constipation, nausea and vomiting in
      cancer patients who received oral opioid analgesics for the first time. METHODS:
      A multi-institutional retrospective study was carried out, in which 619 eligible
      hospitalized patients receiving oral opioid analgesics for cancer pain were
      enrolled from 35 medical institutions. The primary endpoint was the incidence of
      opioid-induced side effects in patients receiving prophylactic medication. Odds
      ratios of the incidence of adverse reactions in the absence or presence of
      premedication obtained from several institutions were subjected to a meta
      analysis. RESULTS: Among 619 patients, the incidence of constipation was
      significantly lower in patients receiving laxatives, including magnesium oxide,
      as premedication than in those without them (34% vs. 55%, odds ratio=0.432, 95%
      confidence interval=0.300-0.622, P<0.001). However, the incidence of nausea or
      vomiting was similar regardless of prophylactic medication with dopamine D2
      blockers. The results of the meta-analysis revealed that prophylactic laxatives
      significantly reduced the incidence of constipation (overall odds ratio=0.469,
      95% confidence interval=0.231-0.955, P=0.037), whereas dopamine D2 blockers were
      not effective in preventing opioid-induced nausea or vomiting. DISCUSSION: We
      showed evidence for the effectiveness of premedication with laxatives for
      prevention of opioid-induced constipation. However, premedication with dopamine
      D2 blockers was not sufficient to prevent nausea or vomiting.

PMID- 22156894
TI  - Which algorithm should be used to screen for syphilis?
AB  - PURPOSE OF REVIEW: A growing number of laboratories have implemented a reverse
      screening algorithm for syphilis testing, which has created confusion among many
      healthcare providers. This review focuses on recent data addressing the clinical
      and economical impact of reverse screening and discusses the advantages and
      limitations of the traditional and contemporary algorithms. RECENT FINDINGS:
      Screening for syphilis using a treponemal assay detects a higher number of
      patients with reactive results compared to traditional screening by rapid plasma
      reagin (RPR). Furthermore, a significant percentage of patients who are reactive
      by a treponemal screening assay are nonreactive by RPR. These discordant results
      may occur in patients with past, treated or untreated syphilis; early syphilis;
      or no syphilis. Recent reports suggest that the reverse screening algorithm may
      result in increased patient follow-ups, overtreatment, and potentially higher
      cost. However, other data suggest that reverse screening facilitates the
      detection of latent and early syphilis, while offering an objective and automated
      screening approach. SUMMARY: The Centers for Disease Control and Prevention
      currently recommends syphilis screening with a nontreponemal test. However, as
      laboratories continue to implement the reverse screening algorithm, it is
      important that samples with discordant screen-reactive, RPR-nonreactive results
      be tested by a second treponemal assay to assist in the interpretation of
      results.

PMID- 22156895
TI  - Periodic presumptive treatment of curable sexually transmitted infections among
      sex workers:  recent experience with implementation.
AB  - PURPOSE OF REVIEW: Curable sexually transmitted infections (STIs) are common
      occupational hazards for female sex workers in low-income and middle-income
      countries. Yet, most infections are asymptomatic and sensitive screening tests
      are rarely affordable or feasible. Periodic presumptive treatment (PPT) has been
      used as a component of STI control interventions to rapidly reduce STI
      prevalence. RECENT FINDINGS: Six recent observational studies confirm earlier
      randomized controlled trial findings that PPT reduces gonorrhoea and chlamydia
      prevalence among sex workers. One modeling study estimated effects on Neisseria
      gonorrhoeae, Chlamydia trachomatis, Haemophilus ducreyi, and HIV prevalence at
      different levels of PPT coverage and frequency, among sex workers who take PPT
      and among all sex workers. Important operational issues include use of single
      dose combination antibiotics for high cure rates, conditions for introducing PPT,
      frequency and coverage, and use of PPT together with other intervention
      components to maximize and sustain STI control and reinforce HIV prevention.
      SUMMARY: PPT is an effective short-term measure to rapidly reduce prevalence of
      gonorrhoea, chlamydia, and ulcerative chancroid among female sex workers. It
      should be implemented together with other measures--to increase condom use,
      reduce risk and vulnerability--in order to maintain low STI prevalence when PPT
      is phased out.

PMID- 22156896
TI  - Women and HIV:  motherhood and more.
AB  - PURPOSE OF REVIEW: The number of women living with HIV continues to increase
      globally. With the availability of efficacious antiretroviral therapy, there is a
      pressing need to ensure women are treated effectively throughout their life
      course. This article reviews information on ways that HIV affects women and
      discusses recent treatment and prevention approaches. RECENT FINDINGS: Because
      women are at greater risk of heterosexual HIV acquisition than men, new data on
      biomedical approaches to prevention are of particular relevance. International
      guidelines for the treatment of pregnant women with HIV now place greater weight
      on the well being of the mother as well as the prevention of vertical
      transmission. Although effective HIV treatment for women is associated with
      better health, longer life, reduced infectiousness and prevention of acquisition
      of HIV, there is evidence that women experience more adverse effects, discontinue
      medication more frequently and have more problems with adherence than men.
      SUMMARY: Efficacious anti-HIV drugs exist, but the particular circumstances for
      women may compromise their effectiveness. Globally, women's access to therapy
      remains inadequate. More data are needed about the best approaches to HIV therapy
      for women to include the biological, psychological, social and cultural factors
      that influence the way women experience HIV infection.

PMID- 22156897
TI  - Neurocognitive dysfunction in the highly active antiretroviral therapy era.
AB  - PURPOSE OF REVIEW: The aim is to review the recent confirmation of the continued
      high prevalence of HIV-associated neurocognitive disorders (HAND) despite highly
      active antiretroviral therapy (HAART) in a large cohort study and to review the
      recent studies that have begun to address the potential reasons for such
      persistence. RECENT FINDINGS: HAND remains prevalent, despite effective viral
      suppression in cerebrospinal fluid and plasma. Several studies have shown the
      benefit of a central nervous system (CNS) penetrating HAART regimen (neuro-HAART)
      in improving neurocognitive outcomes. New evidence supports the early initiation
      of HAART. There are recent data to suggest that HAART may be CNS toxic, but
      evidence is still limited. Ageing does not currently explain the persistence of
      HAND. A recent study has also shown a correlation between cardiovascular risk
      factors and HAND. SUMMARY: The prevalence of HAND remains high in the HAART era.
      Most studies point towards the benefit of neuro-HAART in the prevention and
      treatment of HAND. The possible neurotoxicity of HAART needs to be further
      evaluated. It may be too early to detect a combined ageing and HIV effect and
      long-term studies are required. The link between cardiovascular disease and
      neurocognitive decline in HIV needs further exploration. Effective screening in
      clinical practice is paramount in prevention of the morbidity and mortality
      associated with HAND.

PMID- 22156898
TI  - HIV-1 superinfection.
AB  - PURPOSE OF REVIEW: This review describes the nature and frequency of HIV-1
      superinfection and provides advice regarding counselling of patients in
      accordance with national guidelines. RECENT FINDINGS: Recent studies have
      demonstrated conflicting results, from no superinfection to an incidence of over
      18%. We discuss the difficulties comparing studies due to population and
      methodological differences. SUMMARY: HIV-infected individuals should be
      counselled that there is risk of superinfection at all stages of HIV, but this is
      unlikely to be clinically significant unless transmission of resistance occurs.
      The risk may be as high as the risk of new incident infection in the presence of
      on-going exposure.

PMID- 22156899
TI  - Causes of death in the HAART era.
AB  - PURPOSE OF REVIEW: Compared with vast literature on the clinical, imaging, and in
      vivo microbiology aspects of HIV disease, there is less on biopsy pathology and
      even less on autopsy data. This review focuses on some current clinico
      pathological issues, with indications of where there is less certainty than we
      would like. RECENT FINDINGS: The most important change in causes of death in HIV
      disease, since the advent of highly active antiretroviral therapy (HAART), is the
      reduction of classical AIDS-defining opportunistic diseases, with the
      compensating increase in background comorbidities related to lifestyle,
      infections including the hepatitis viruses and HHV8, ageing, drug toxicity and
      immune reconstitution inflammatory syndrome phenomena. In low-income countries,
      HIV contributes significantly to maternal mortality. SUMMARY: To understand HIV
      disease better and manage future patients better, we need more tissue clinico
      pathological correlation, including quality biopsy and autopsy evaluations.

PMID- 22156900
TI  - Low-level viraemia on HAART:  significance and management.
AB  - PURPOSE OF REVIEW: The source, significance and optimal management of low-level
      viraemia during highly active antiretroviral therapy (HAART) are poorly defined.
      This review highlights recent observations that have implications for clinical
      practice. RECENT FINDINGS: The definition of low-level viraemia remains elusive.
      Whereas evidence obtained with second-generation viral load assays indicates that
      confirmed detection of plasma HIV-1 RNA above 50  copies/ml predicts negative
      outcomes, third-generation assays detect HIV-1 RNA below this threshold. In
      patients monitored with the Abbott RealTime assay, the cutoff that should trigger
      confirmation of viraemia and clinical review can be revised to 40  copies/ml.
      Further data are needed on the cost-effectiveness of intervening when RNA
      detection is observed below this cutoff. Discrepancies among viral load assays
      prevent generalization of these observations. To further compound the issue, most
      patients on stably suppressive HAART show residual viraemia at around 1-10 
      copies/ml using research-based ultrasensitive assays. The source of residual
      viraemia remains controversial, but neither short nor long-term HAART
      intensification with antiretrovirals such as raltegravir reduces the viraemia. A
      transient effect of intravenous immunoglobulin has been reported, and different
      regimens may vary in their propensity to allow HIV-1 RNA persistence. Further
      studies are required to clarify the relationship between low-level viraemia and
      the size of proviral DNA reservoirs, and the contribution of cellular and tissue
      compartments and cell-to-cell spread to ongoing virus replication during HAART.
      SUMMARY: Understanding the source and clinical significance of HIV-1 RNA
      persistence in plasma during HAART is required to guide patient care and inform
      the design of HIV eradication strategies.

PMID- 22156901
TI  - Tenofovir-based pre-exposure prophylaxis for HIV prevention:  evolving evidence.
AB  - PURPOSE OF REVIEW: Topical tenofovir gel and oral tenofovir and emtricitabine
      tenofovir [FTC/tenofovir disoproxyl fumarate (TDF)] have been demonstrated to
      have efficacy in preventing HIV-1 in some populations. Preexposure prophylaxis
      (PrEP) trials and future directions are summarized. RECENT FINDINGS: Pericoital
      use of 1% tenofovir gel in the CAPRISA 004 study reduced HIV-1 acquisition by 39%
      and herpes simplex virus-2 acquisition by 51%. Daily oral FTC/TDF demonstrated
      44% reduction in HIV-1 acquisition among MSM in the iPrEx study (Pre-Exposure
      Prophylaxis Initiative). Both studies showed higher efficacy among those with
      higher adherence. Efficacy of daily oral TDF and FTC/TDF was 66 and 73%,
      respectively, among HIV-1-uninfected partners in an HIV-1 serodiscordant
      partnership in the Partners PrEP Study. Efficacy of daily oral FTC/TDF was 66% in
      young heterosexuals in Botswana in the TDF2 trial. The FEM-PrEP and VOICE
      (Vaginal and Oral Interventions to Control the Epidemic) studies in African women
      found no efficacy with oral FTC/TDF and TDF, respectively. Safety and
      tolerability were excellent and limited resistance was observed in
      seroconverters. SUMMARY: Topical tenofovir gel showed efficacy in African women
      and daily oral TDF and FTC/TDF were efficacious in MSM, and African HIV-1
      serodiscordant couples and young heterosexuals. The reasons for lack of efficacy
      of oral FTC/TDF and TDF in two studies in African women are being investigated.
      Longer-acting formulations, invtravaginal rings, and new candidate
      antiretrovirals are being evaluated for pre-exposure prophylaxis (PrEP).

PMID- 22156902
TI  - What is the role of steroids in pneumonia therapy?
AB  - PURPOSE OF REVIEW: This review evaluates the potential benefits as well as
      adverse effects from adjunctive therapy with systemic steroids in patients with
      pneumonia: either mild-to-moderate or severe, community-acquired or hospital
      acquired, of bacterial or of viral origin (in particular H1N1 viral infection).
      RECENT FINDINGS: Steroids potentially modulate the marked and persistent
      activation of the immune system in pneumonia. However, several recent randomized
      controlled trials and large prospective observational studies have repeatedly
      shown that steroids had no impact on survival, the clinical event of interest,
      but in severe pneumonia some studies pointed to potential harmful effect. In
      addition, adverse effects, namely hyperglycemia, superinfections, as well as
      increased length-of-stay, were frequent findings in the steroid-treated patients.
      SUMMARY: According to the current evidence, there are no data to support the well
      tolerated use of systemic steroids as a standard of care in pneumonia, neither in
      mild-to-moderate and severe, nor in bacterial and viral infection. Clinical and
      basic research should work together to improve trial designs to identify reliable
      surrogate markers of outcome, in particular of mortality. This may improve the
      patient selection and facilitate the identification of subgroups that can benefit
      from adjunctive steroid therapy.

PMID- 22156903
TI  - High-intensity focused ultrasound as an alternative to the surgical approach in
      primary hyperparathyroidism: a preliminary experience.
AB  - BACKGROUND: Surgery is the therapy of choice in primary hyperparathyroidism
      (PHPT), although other less invasive techniques have been used in the attempt to
      cure the disease. Recently, high-intensity focused ultrasound (HIFU), a totally
      non-invasive technique, has become available to cure solid tumors. AIM: The aim
      of this pilot study has been to assess the safety and efficacy of HIFU in
      symptomatic patients with PHPT. MATERIAL AND METHODS: Four out of 31 patients
      with surgical indications within a cohort of 47-screened patients with PHPT were
      considered eligible for the study. All patients accepted to participate and were
      submitted to HIFU treatment in a single session. One patient was submitted to
      surgery after HIFU treatment. Patients were followed-up for 12 months after the
      procedure. RESULTS: A persistent or a partial remission of the disease,
      respectively, were obtained in 2 patients (50%), including the one who underwent
      surgery after HIFU treatment. Safety was assessed performing laryngoscopy in all
      patients after HIFU procedure. A transient vocal cord paralysis was observed in
      all patients treated by HIFU only. No permanent side effects were observed in the
      long term. CONCLUSIONS: HIFU might be a promising technique in treating PHPT,
      provided that further development of the software decreases the rate of side
      effects and improves the short- and long-term efficacy.

PMID- 22156904
TI  - Hypoglycemia and insulin treatment.

PMID- 22156905
TI  - The metabolic syndrome among obese adolescents.

PMID- 22156906
TI  - SOM230 in Cushing's disease complicated by poorly controlled diabetes mellitus.

PMID- 22156907
TI  - The role of tumor-infiltrating lymphocytes in papillary thyroid carcinomas.

PMID- 22156908
TI  - Subclinical Addison's disease mimicking a silent corticotroph adenoma.

PMID- 22156909
TI  - Endocrinology and art. A noblewoman with goiter - Ritratto di gentildonna
      Prospero Fontana (1512-1597).

PMID- 22156910
TI  - A randomized controlled trial to evaluate the effectiveness of a board game on
      patients' knowledge uptake of HIV and sexually transmitted diseases at the
      Infectious Diseases Institute, Kampala, Uganda.
AB  - BACKGROUND: As the number of HIV infections continues to rise, the search for
      effective health education strategies must intensify. A new educational board
      game was developed to increase HIV peoples' attention and knowledge to HIV and
      sexually transmitted infections (STIs) information. The object of this study was
      to assess the effect of this educational board game on the uptake of knowledge.
      METHODS: A randomized controlled trial where patients attending the Infectious
      Diseases Clinic, Kampala, Uganda were randomized to either play the board game
      (intervention arm) or to attend a health talk (standard of care arm).
      Participants' knowledge was assessed before and after the education sessions
      through a questionnaire. RESULTS: One hundred eighty HIV-positive participants
      were enrolled, 90 for each study arm. The pretest scores were similar for each
      arm. There was a statistically significant increase in uptake of knowledge of HIV
      and STIs in both study arms. Compared with patients in the standard of care arm,
      participants randomized to the intervention arm had higher uptake of knowledge
      (4.7 points, 95% confidence interval: 3.9 to 5.4) than the controls (1.5 points,
      95% confidence interval: 0.9 to 2.1) with a difference in knowledge uptake
      between arms of 3.2 points (P < 0.001). Additionally, both participants and
      facilitators preferred the board game to the health talk as education method.
      CONCLUSIONS: The educational game significantly resulted in higher uptake of
      knowledge of HIV and STIs. Further evaluation of the impact of this educational
      game on behavioral change in the short and long term is warranted.

PMID- 22156911
TI  - Increased platelet and microparticle activation in HIV infection: upregulation of
      P-selectin and tissue factor expression.
AB  - OBJECTIVE: HIV-1-infected patients have an increased risk for atherothrombosis
      and cardiovascular disease, but the mechanism behind these risks is poorly
      understood. We have previously reported that expression of tissue factor (TF) on
      circulating monocytes is increased in persons with HIV infection and that TF
      expression is related to immune activation, to levels of HIV in plasma, and to
      indices of microbial translocation. In this study, we explore the activation
      state of platelets in HIV disease. METHODS: Here, using flow cytometry-based
      assays, we measured platelet and platelet microparticle (PMP) activation in
      samples from HIV-1-infected donors and controls. RESULTS: Platelets and PMPs from
      HIV-1-infected patients are activated (as reflected by expression of CD62 P
      selectin) and also more frequently expressed the procoagulant TF than did
      platelets and PMPs obtained from controls. Expression of these proteins was
      directly related to expression of TF on monocytes, to markers of T-cell
      activation (CD38 and HLA-DR), and to plasma levels of soluble CD14, the
      coreceptor for bacterial lipopolysaccharride. Platelet and microparticle
      expression of TF was not related to plasma levels of HIV but expression of P
      selectin was related to plasma levels of HIV; neither TF nor P-selectin
      expression was related to CD4 T-cell count. CONCLUSIONS: Platelets and
      microparticles are activated in HIV infection, and this activated phenotype may
      contribute to the increased risk for cardiovascular and thrombotic events in this
      population although a role for other confounding cardiovascular risks cannot be
      completely excluded.

PMID- 22156912
TI  - Excellent clinical outcomes and high retention in care among adults in a
      community-based HIV treatment program in rural Rwanda.
AB  - BACKGROUND: Access to antiretroviral therapy (ART) has rapidly expanded; as of
      the end of 2010, an estimated 6.6 million people are receiving ART in low-income
      and middle-income countries. Few reports have focused on the experiences of rural
      health centers or the use of community health workers. We report clinical and
      programatic outcomes at 24 months for a cohort of patients enrolled in a
      community-based ART program in southeastern Rwanda under collaboration between
      Partners In Health and the Rwandan Ministry of Health. METHODS AND FINDINGS: A
      retrospective medical record review was performed for a cohort of 1041 HIV+ adult
      patients initiating community-based ART between June 1, 2005, and April 30, 2006.
      Key programatic elements included free ART with direct observation by community
      health worker, tuberculosis screening and treatment, nutritional support, a
      transportation allowance, and social support. Among 1041 patients who initiated
      community-based ART, 961 (92.3%) were retained in care, 52 (5%) died and 28
      (2.7%) were lost to follow-up. Median CD4 T-cell count increase was 336 cells per
      microliter [interquartile range: (IQR): 212-493] from median 190 cells per
      microliter (IQR: 116-270) at initiation. CONCLUSIONS: A program of intensive
      community-based treatment support for ART in rural Rwanda had excellent outcomes
      in 24-month retention in care. Having committed to improving access to HIV
      treatment in sub-Saharan Africa, the international community, including country
      HIV programs, should set high programmatic outcome benchmarks.

PMID- 22156913
TI  - Small dense lipoproteins, apolipoprotein B, and risk of coronary events in HIV
      infected patients on antiretroviral therapy: the Swiss HIV Cohort Study.
AB  - OBJECTIVES: HIV infection and exposure to certain antiretroviral drugs is
      associated with dyslipidemia and increased risk for coronary events. Whether this
      risk is mediated by highly atherogenic lipoproteins is unclear. We investigated
      the association of highly atherogenic small dense low-density lipoproteins (LDLs)
      and apolipoprotein B and coronary events in HIV-infected individuals receiving
      antiretroviral therapy. METHODS: We conducted a case-control study nested into
      the Swiss HIV Cohort Study to investigate the association of small dense LDL and
      apolipoprotein B and coronary events in 98 antiretroviral drug-treated patients
      with a first coronary event (19 fatal and 79 nonfatal coronary events with 53
      definite and 15 possible myocardial infarctions, 11 angioplasties or bypasses)
      and 393 treated controls matched for age, gender, and smoking status. Lipids were
      measured by ultracentrifugation. RESULTS: In models including cholesterol,
      triglycerides, high-density lipoprotein cholesterol, blood pressure, central
      obesity, diabetes, and family history, there was an independent association
      between small dense LDL and coronary events [odds ratio (OR) for 1 mg/dL
      increase: 1.06, 95% confidence interval (CI): 1.00 to 1.11] and apolipoprotein B
      (OR for 10 mg/dL increase: 1.16, 95% CI: 1.02 to 1.32). When adding HIV and
      antiretroviral therapy-related variables, ORs were 1.04 (95% CI: 0.99 to 1.10)
      for small dense LDL and 1.13 (95% CI: 0.99 to 1.30) for apolipoprotein B. In both
      models, blood pressure and HIV viral load was independently associated with the
      odds for coronary events. CONCLUSIONS: HIV-infected patients receiving
      antiretroviral therapy with elevate small dense LDL and apolipoprotein B are at
      increased risk for coronary events as are patients without sustained HIV
      suppression.

PMID- 22156914
TI  - A new syndromic craniosynostosis with involvement of the spine, long bones,
      pelvis, and digits: molecular genetic and array analysis.

PMID- 22156915
TI  - Coordinating cell cycle progression via cyclin specificity.

PMID- 22156916
TI  - Perspectives on PACS: where is caries prevention clinical research going?

PMID- 22156918
TI  - A quantitative structure-activity relationship (QSAR) study on glycan array data
      to determine the specificities of glycan-binding proteins.
AB  - Advances in glycan array technology have provided opportunities to automatically
      and systematically characterize the binding specificities of glycan-binding
      proteins. However, there is still a lack of robust methods for such analyses. In
      this study, we developed a novel quantitative structure-activity relationship
      (QSAR) method to analyze glycan array data. We first decomposed glycan chains
      into mono-, di-, tri- or tetrasaccharide subtrees. The bond information was
      incorporated into subtrees to help distinguish glycan chain structures. Then, we
      performed partial least-squares (PLS) regression on glycan array data using the
      subtrees as features. The application of QSAR to the glycan array data of
      different glycan-binding proteins demonstrated that PLS regression using subtree
      features can obtain higher R(2) values and a higher percentage of variance
      explained in glycan array intensities. Based on the regression coefficients of
      PLS, we were able to effectively identify subtrees that indicate the binding
      specificities of a glycan-binding protein. Our approach will facilitate the
      glycan-binding specificity analysis using the glycan array. A user-friendly web
      tool of the QSAR method is available at
      http://bci.clemson.edu/tools/glycan_array.

PMID- 22156917
TI  - Efficacy of chlorhexidine varnish for the prevention of adult caries: a
      randomized trial.
AB  - The Prevention of Adult Caries Study, an NIDCR-funded multicenter, double-blind,
      randomized clinical trial, enrolled 983 adults (aged 18-80 yrs) at high risk for
      developing caries (20 or more intact teeth and 2 or more lesions at screening) to
      test the efficacy of a chlorhexidine diacetate 10% weight per volume (w/v) dental
      coating (CHX). We excluded participants for whom the study treatment was
      contraindicated or whose health might affect outcomes or ability to complete the
      study. Participants were randomly assigned to receive either the CHX coating (n =
      490) or a placebo control (n = 493). Coatings were applied weekly for 4 weeks and
      a fifth time 6 months later. The primary outcome (total net D(1-2)FS increment)
      was the sum of weighted counts of changes in tooth surface status over 13 months.
      We observed no significant difference between the two treatment arms in either
      the intention-to-treat or per-protocol analyses. Analysis of 3 protocol-specified
      secondary outcomes produced similar findings. This trial failed to find that 10%
      (w/v) chlorhexidine diacetate coating was superior to placebo coating for the
      prevention of new caries (Clinicaltrials.gov registration number NCT00357877).

PMID- 22156919
TI  - Structural features for alpha-galactomannan binding to galectin-1.
AB  - Galectins have a highly conserved carbohydrate-binding domain to which a variety
      of galactose-containing saccharides, both beta- and alpha-galactosides, can
      interact with varying degrees of affinity. Recently, we demonstrated that the
      relatively large alpha(1 -> 6)-D-galacto-beta(1 -> 4)-D-mannan (Davanat) binds
      galectin-1 (gal-1) primarily at an alternative carbohydrate-binding domain. Here,
      we used a series of alpha-galactomannans (GMs) that vary in their mannose-to
      galactose ratios for insight into an optimal structural signature for GM binding
      to gal-1. Heteronuclear single-quantum coherence nuclear magnetic resonance
      spectroscopy with (15)N-labeled gal-1 and statistical modeling suggest that the
      optimal signature consists of alpha-D-galactopyranosyl doublets surrounded by
      regions of about four or more "naked" mannose residues. These relatively large
      and complex GMs all appear to interact with varying degrees at essentially the
      same binding surface on gal-1 that includes the Davanat alternative binding site
      and elements of the canonical beta-galactoside-binding region. The use of two
      small, well-defined GMs [6(1)-alpha(1 -> 6)-D-galactosyl-beta-D-mannotriaose and
      6(3),6(4)-di-alpha(1 -> 6)-D-galactosyl-beta-D-mannopentaose] helped characterize
      how GMs, in general, interact in part with the canonical site. Overall, our
      findings contribute to better understanding interactions of gal-1 with larger,
      complex polysaccharides and to the development of GM-based therapeutics for
      clinical use.

PMID- 22156920
TI  - Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in
      chondroitin sulfate initiation: Impact of sulfation on activity and specificity.
AB  - Glycosaminoglycan (GAG) assembly initiates through the formation of a linkage
      tetrasaccharide region serving as a primer for both chondroitin sulfate (CS) and
      heparan sulfate (HS) chain polymerization. A possible role for sulfation of the
      linkage structure and of the constitutive disaccharide unit of CS chains in the
      regulation of CS-GAG chain synthesis has been suggested. To investigate this, we
      determined whether sulfate substitution of galactose (Gal) residues of the
      linkage region or of N-acetylgalactosamine (GalNAc) of the disaccharide unit
      influences activity and specificity of chondroitin sulfate N
      acetylgalactosaminyltransferase-1 (CSGalNAcT-1), a key glycosyltransferase of CS
      biosynthesis. We synthesized a series of sulfated and unsulfated analogs of the
      linkage oligosaccharide and of the constitutive unit of CS and tested these
      molecules as potential acceptor substrates for the recombinant human CSGalNAcT-1.
      We show here that sulfation at C4 or C6 of the Gal residues markedly influences
      CSGalNAcT-1 initiation activity and catalytic efficiency. Kinetic analysis
      indicates that CSGalNAcT-1 exhibited 3.6-, 1.6-, and 2.2-fold higher enzymatic
      efficiency due to lower K(m) values toward monosulfated trisaccharides
      substituted at C4 or C6 position of Gal1, and at C6 of Gal2, respectively,
      compared with the unsulfated oligosaccharide. This highlights the critical
      influence of Gal substitution on both CSGalNAcT-1 activity and specifity. No
      GalNAcT activity was detected toward sulfated and unsulfated analogs of the CS
      constitutive disaccharide (GlcA-beta1,3-GalNAc), indicating that CSGalNAcT-1 was
      involved in initiation but not in elongation of CS chains. Our results strongly
      suggest that sulfation of the linkage region acts as a regulatory signal in CS
      chain initiation.

PMID- 22156922
TI  - Aligning resources to fight HIV/AIDS in the United States: funding to states
      through the US Department of Health and Human Services.
AB  - BACKGROUND: In response to the first U.S. National HIV/AIDS Strategy released in
      July 2010, we assessed how HIV/AIDS funding is spent by the Department of Health
      and Human Services (HHS) and how these resources align geographically with the
      HIV/AIDS epidemic according to various measures. METHODS: Estimated FY2010
      spending information was gathered from HHS agencies, including state/territory
      level spending by prevention, care, and treatment services of the Centers for
      Disease Control and Prevention (CDC), Health Resources and Services
      Administration (HRSA), and Substance Abuse and Mental Health Services
      Administration (SAMHSA) - as well as Centers for Medicare and Medicaid Services
      (CMS). HHS funding is presented descriptively by state in the context of living
      HIV and AIDS case numbers and rates. RESULTS: Nearly US$16 billion went to
      discretionary and entitlement spending, 77% of which supported or provided care
      and treatment by CMS (Medicare, Medicaid) and HRSA; the remainder to research,
      prevention, and other activities. For states and territories overall, funding was
      highly correlated with living AIDS case numbers (R(2) = .88) as well as living
      HIV case numbers (R(2) = .84); funding was far less correlated with case rates
      (per 100,000 population) for AIDS (R(2) = .35) or HIV (R(2) = .42). CONCLUSIONS:
      HHS HIV/AIDS funding, overall, is well correlated with the number of HIV/AIDS
      cases in each state/territory. Future assessments should capture information on
      who is being served, where, and how.

PMID- 22156921
TI  - Pregabalin beneficial effects on sleep quality or health-related quality of life
      are poorly correlated with reduction on pain intensity after an 8-week treatment
      course.
AB  - BACKGROUND: Pregabalin (PGB) has been shown to improve sleep quality and health
      related quality of life (HRQoL) as well as pain intensity in patients with
      neuropathic pain. OBJECTIVE: The objective of the study was to explore the
      magnitude of the correlations between changes in pain intensity, sleep quality,
      and HRQoL after PGB treatment. METHODS: One hundred thirty-eight patients with
      neuropathic pain of any origin and without an adequate response to analgesics
      received an 8-week treatment course of PGB in an open-label fashion. Pain
      intensity, sleep quality, and HRQoL outcomes were evaluated at baseline and at
      week 8 by means of an 11-point (0-10) numerical rating scale (NRS), the
      Pittsburgh Sleep Quality Index (PSQI), and the EuroQol health-state visuoanalogic
      scale (EQ-5D VAS) score, respectively. RESULTS: At week 8, mean PGB dose was
      166.7 +/- 7.8 mg/d. Pain intensity NRS score, PSQI total score, and EQ-5D VAS
      score were improved by 66.5% +/- 1.9%, 40.0% +/- 3.6%, and 26.4% +/- 4.7% (all P
      < 0.01), respectively. Correlations between percent change from baseline in pain
      NRS score and PSQI total score or EQ-5D VAS scores were r = 0.36 (P < 0.01, R =
      0.11) and r = -0.20 (P < 0.02, R = 0.05), respectively. A multivariate logistic
      regression analysis disclosed that PSQI score change below the median (ie, a
      better outcome) was related to higher EQ-5D VAS score change (odds ratio, 2.15;
      95% confidence interval, 1.09-4.25), whereas pain intensity NRS score change
      below the median was not (odds ratio, 1.58; 95% confidence interval,0.78-3.23).
      CONCLUSIONS: In our study, PGB-related improvements in sleep quality and HRQoL
      were marginally related to reductions in pain intensity in patients with
      neuropathic pain. Improvement in sleep quality was a significant predictor of
      better HRQoL, whereas pain intensity reduction was not.

PMID- 22156923
TI  - Correlation between radiographic classification and pathological grade of portal
      vein wall invasion in pancreatic head cancer.
AB  - OBJECTIVES: A retrospective study was performed to clarify the correlation
      between radiographic type of portal vein (PV) invasion and pathological grade of
      PV wall invasion, and their correlation with postoperative prognosis. BACKGROUND:
      In many patients with pancreatic cancer, PV resection is necessary to increase
      resectability and obtain cancer-free margins. METHODS: We analyzed 671 patients
      who had undergone surgery for invasive adenocarcinoma of the pancreas between
      July 1981 and June 2010. Radiographic types of PV invasion of pancreatic head
      cancer were classified into A (normal), B (unilateral narrowing), C (bilateral
      narrowing), or D (complete obstruction with collateral veins), by portography or
      computed tomography. Pathological grades of PV wall invasion were classified as 0
      (no invasion), 1 (tunica adventitia), 2 (tunica media), or 3 (tunica intima).
      RESULTS: Four hundred and sixty-three patients underwent resection, and PV
      resection was performed in 297. Combined arterial vessel resection was performed
      in 16 cases. No significant difference in operative mortality was observed
      between PV preservation (0.6%) and PV-only resection (2.1%), and no operative
      deaths occurred after 1999. Radiographic classification of PV invasion correlated
      with incidence of pathological PV wall invasion. In pancreatic head carcinoma, no
      pathological PV wall invasion was observed in type A (n = 111). Pathological PV
      invasion was observed in 51% of type B (42/82), 74% of type C (72/97), and 93% of
      type D (63/68). Long-term survival (>5 years) was observed in types A and B, and
      grades 0 and 1 subgroups. CONCLUSIONS: Pancreatectomy with PV resection can be
      performed safely. Even in radiographic classification type B, pathological PV
      wall invasion was observed in 51% of patients. Long-term survival was observed in
      types A and B, and grades 0 and 1.

PMID- 22156924
TI  - Angiogenesis in synchronous and metachronous colorectal liver metastases: the
      liver as a permissive soil.
AB  - OBJECTIVE: Resection of a primary colorectal carcinoma (CRC) can be accompanied
      by rapid outgrowth of liver metastases, suggesting a role for angiogenesis. The
      aim of this study is to investigate whether the presence of a primary CRC is
      associated with changes in angiogenic status and proliferation/apoptotic rate in
      synchronous liver metastases and/or adjacent liver parenchyma. METHODS: Gene
      expression and localization of CD31, HIF-1alpha, members of the vascular
      endothelial growth factor (VEGF) and Angiopoietin (Ang) system were studied using
      qRT-PCR and immunohistochemistry in colorectal liver metastases and nontumorous
      adjacent liver parenchyma. Proliferation and apoptotic rate were quantified.
      Three groups of patients were included: (1) simultaneous resection of synchronous
      liver metastases and primary tumor (SS-group), (2) resection of synchronous liver
      metastases 3 to 12 months after resection of the primary tumor [late synchronous
      (LS-group)], and (3) resection of metachronous metastases >14 months after
      resection of the primary tumor (M-group). RESULTS: In all 3 groups a higher
      expression of the angiogenic factors was encountered in adjacent liver parenchyma
      as compared to the metastases. VEGFR-2 gene expression was abundant in adjacent
      liver parenchyma in all 3 groups. VEGF-A and VEGFR-1 were prominent in adjacent
      parenchyma in the SS-group. The SS-group showed the highest Ang-2/Ang-1 ratio
      both in the metastases and the adjacent liver. This was accompanied by a high
      turnover of tumor cells. CONCLUSION: In the presence of the primary tumor, the
      liver parenchyma adjacent to the synchronous liver metastases provides an
      angiogenic prosperous environment for metastatic tumor growth.

PMID- 22156925
TI  - National variation in outcomes and costs for splenic injury and the impact of
      trauma systems: a population-based cohort study.
AB  - OBJECTIVE: To measure national variation in splenectomy rates, mortality, and
      costs for hospitalized patients with splenic injury and the impact of state
      trauma systems on these outcomes. METHODS: Using the HCUP State Inpatient
      Database for 2001, 2004, and 2007, all patients hospitalized with splenic injury
      were identified from 19 participating states. Multivariate regression was
      performed to compare splenectomy rates, inpatient mortality, and costs between
      states. Inclusiveness of statewide trauma systems was categorized based on the
      proportion of hospitals designated as a trauma center. RESULTS: Of 33,131
      patients, 26.2% underwent splenectomy, 6.1% died, and median hospital costs were
      $14,317. After adjusting for patient, injury, and hospital characteristics, there
      was a 1.7-fold variation (RR 1.67; 95% CI, 1.39-2.01) among the 19 states in
      rates of splenectomy. Adjusted inpatient mortality varied more than 2-fold
      between the highest and lowest states (RR 2.43; 95% CI, 1.76-3.37). Adjusted
      hospital costs varied over 60% between the highest and lowest states (cost ratio
      1.61; 95% CI, 1.41-1.83). States with the most inclusive trauma systems had
      significantly lower splenectomy rate (RR 0.79; 95% CI, 0.68-0.92) and lower
      mortality (RR 0.71; 95% CI, 0.58-0.87), but similar hospital costs (CR 1.05; 95%
      CI, 0.95-1.16) compared to states with exclusive or no trauma systems.
      CONCLUSIONS: Significant geographic variation in the management, outcome, and
      costs for splenic injury exists in the United States, and may reflect differences
      in quality of care. Inclusive trauma systems seem to improve outcomes without
      increasing hospital costs.

PMID- 22156926
TI  - Infusion of CD133+ bone marrow-derived stem cells after selective portal vein
      embolization enhances functional hepatic reserves after extended right
      hepatectomy: a retrospective single-center study.
AB  - OBJECTIVE: This study was designed to evaluate the clinical outcome of patients
      undergoing portal vein embolization (PVE) and autologous CD133 bone marrow
      derived stem cell (CD133+ BMSC) application before extended right hepatectomy.
      BACKGROUND: We have previously shown that portal venous infusion of CD133+ BMSCs
      substantially increases hepatic proliferation, when compared with PVE alone.
      METHODS: : Among 40 consecutive patients with a median follow-up of 28 months
      (7.4-57.2) scheduled for extended right hepatectomy, we compared a preconditioned
      group with PVE and CD133+ BMSC cotreatment (PVE+SC group, n = 11) and a group
      pretreated only with PVE (PVE group, n = 11). Functional and overall outcomes
      after extended right hepatectomy were evaluated. Patients without presurgical
      treatment served as controls (n = 18). RESULTS: In preconditioned patients, mean
      hepatic growth of segments II/III 14 days after PVE in the PVE+SC group was
      significantly higher (138.66 mL +/- 66.29) when compared with that of PVE group
      patients (62.95 mL +/- 40.03; P = 0.004). There were no significant differences
      among all 3 groups regarding general and oncological characteristics and
      functional parameters on postoperative day (POD) 7. Lack of hepatic
      preconditioning, extrahepatic extension of resection, and postoperative
      complications were of negative prognostic value, using univariate analysis (P <
      0.05). In multivariate analysis, freedom from postoperative major complications
      (P = 0.012), coagulation status on POD 7 (international normalized ratio < 1.4; P
      = 0.027), and presurgical expansion of the future liver remnant volume (P =
      0.048) were positively associated with overall survival. Post hoc analysis
      revealed a better survival for the PVE+SC group (P = 0.028) compared with the PVE
      group (P = 0.094) and compared with controls. CONCLUSION: Promising data from
      this survival analysis suggest that PVE, together with CD133+ BMSC pretreatment,
      could positively impact overall outcomes after extended right hepatectomy.

PMID- 22156927
TI  - Implementation of molecular phenotyping approaches in the personalized surgical
      patient journey.
AB  - OBJECTIVE: The present review describes commonly employed metabolic profiling
      platforms and discusses the current and likely future application of these
      technologies in surgery. BACKGROUND: The metabolic adaptations that occur in
      response to surgical illness and trauma are incompletely understood. Evaluating
      these will be critical to the development of personalized surgical health
      solutions. Metabonomics is an advancing field in systems biology, which provides
      a means of interrogating these metabolic shifts. METHODS: Recent literature
      regarding metabolic profiling technologies and their applications in surgical
      practice are discussed. Future strategies are proposed for the incorporation of
      these and next-generation technologies in the evaluation of all steps in the
      patient surgical pathway. RESULTS: Metabolite-based profiling has provided
      valuable insights into the metabolic irregularities that occur in cancer
      development and progression across a variety of cancer subclasses including
      colorectal, breast, prostate, and lung cancers. In addition, metabolic modeling
      has shown considerable promise in other surgical conditions including trauma and
      sepsis and in the assessment of pharmacotherapeutic efficacy. DISCUSSION:
      Metabonomics offers a posttranscriptional view of system activity providing
      functional information downstream of the genome and proteome. Information at this
      level will provide the surgeon with a novel means of evaluating major
      socioeconomic problems such as cancer and sepsis. In addition, the rapid nature
      of emerging next generation profiling platforms provides a viable means of "real
      time" perioperative metabolic assessment and optimization.

PMID- 22156929
TI  - Preclinical investigation of nanoparticle albumin-bound paclitaxel as a potential
      treatment for adrenocortical cancer.
AB  - BACKGROUND: Traditional drug discovery methods have a limited role in rare
      cancers. We hypothesized that molecular technology including gene expression
      profiling could expose novel targets for therapy in adrenocortical carcinoma
      (ACC), a rare and lethal cancer. SPARC (secreted protein acidic rich in cysteine)
      is an albumin-binding matrix-associated protein that is proposed to act as a
      mechanism for the increased efficacy of a nanoparticle albumin-bound preparation
      of the antimicrotubular drug Paclitaxel (nab-paclitaxel). METHODS: The
      transcriptomes of 19 ACC tumors and 4 normal adrenal glands were profiled on
      Affymetrix U133 Plus2 expression microarrays to identify genes representing
      potential therapeutic targets. Immunohistochemical analysis for target proteins
      was performed on 10 ACC, 6 benign adenomas, and 1 normal adrenal gland. Agents
      known to inhibit selected targets were tested in comparison with mitotane in the
      2 ACC cell lines (H295R and SW-13) in vitro and in mouse xenografts. RESULTS:
      SPARC expression is increased in ACC samples by 1.56 +/- 0.44 (MU +/- SD) fold.
      Paclitaxel and nab-paclitaxel show in vitro inhibition of H295R and SW-13 cells
      at IC50 concentrations of 0.33 MUM and 0.0078 MUM for paclitaxel and 0.35 MUM and
      0.0087 MUM for nab-paclitaxel compared with mitotane concentrations of 15.9 MUM
      and 46.4 MUM. In vivo nab-paclitaxel treatment shows a greater decrease in tumor
      weight in both xenograft models than mitotane. CONCLUSIONS: Biological insights
      garnered through expression profiling of ACC tumors suggest further investigation
      into the use of nab-paclitaxel for the treatment of ACC.

PMID- 22156928
TI  - Hospital quality and the cost of inpatient surgery in the United States.
AB  - CONTEXT: Payers, policy makers, and professional organizations have launched a
      variety of initiatives aimed at improving hospital quality with inpatient
      surgery. Despite their obvious benefits for patients, the likely impact of these
      efforts on health care costs is uncertain. In this context, we examined
      relationships between hospital outcomes and expenditures in the US Medicare
      population. METHODS: Using the 100% national claims files, we identified all US
      hospitals performing coronary artery bypass graft, total hip replacement,
      abdominal aortic aneurysm repair, or colectomy procedures between 2005 and 2007.
      For each procedure, we ranked hospitals by their risk- and reliability-adjusted
      outcomes (complication and mortality rates, respectively) and sorted them into
      quintiles. We then examined relationships between hospital outcomes and risk
      adjusted, 30-day episode payments. RESULTS: There was a strong, positive
      correlation between hospital complication rates and episode payments for all
      procedures. With coronary artery bypass graft, for example, hospitals in the
      highest complication quintile had average payments that were $5353 per patient
      higher than at hospitals in the lowest quintile ($46,024 vs $40,671, P < 0.001).
      Payments to hospitals with high complication rates were also higher for colectomy
      ($2719 per patient), abdominal aortic aneurysm repair ($5279), and hip
      replacement ($2436). Higher episode payments at lower-quality hospitals were
      attributable in large part to higher payments for the index hospitalization,
      although 30-day readmissions, physician services, and postdischarge ancillary
      care also contributed. Despite the strong association between hospital
      complication rates and payments, hospital mortality was not associated with
      expenditures. CONCLUSIONS: Medicare payments around episodes of inpatient surgery
      are substantially higher at hospitals with high complications. These findings
      suggest that local, regional, and national efforts aimed at improving surgical
      quality may ultimately reduce costs and improve outcomes.

PMID- 22156930
TI  - The business of quality in surgery.

PMID- 22156931
TI  - Are antidepressants useful in the treatment of minor depression:  a critical
      update of the current literature.
AB  - PURPOSE OF REVIEW: In minor depression, the number, severity or duration of
      symptoms are insufficient to diagnose a major depression or dysthymia.
      Nevertheless, minor depression is a prevalent disorder associated with functional
      disability, impairment of quality of life, and intense healthcare use. The aim of
      this article is to discuss the evidence for the effectiveness of antidepressants
      in patients with minor depression taking into account a recent meta-analysis and
      further clinical trials as well as methodological problems associated with the
      common approach to deducing the clinical significance of therapeutic effects of
      antidepressants from placebo-verum differences in randomized clinical trials
      (RCTs). RECENT FINDINGS: A recent meta-analysis, comprising six RCTs, and two
      newer studies do not provide evidence for the efficacy of antidepressants in
      patients with minor depression, but do not have the power and the methodological
      quality to exclude efficacy. Possible risks of underestimating the clinical
      significance of antidepressants based on RCT data are discussed. SUMMARY: For
      minor depression, unspecific support like active monitoring, unspecific group
      counselling or internet-based guided self-help activities are reasonable
      treatment options. Antidepressants can be considered in special cases with, for
      example, suicidality, previous suicide attempts, family history of affective
      disorders or previous major depressive episodes.

PMID- 22156932
TI  - Strategies and challenges in the management of adolescent depression.
AB  - PURPOSE OF REVIEW: Adolescent depression is a chronic, pervasive, and disabling
      problem that is often under-recognized and under-treated. The objective of this
      article is to review recent (over the past 12-18 months) literature on the
      management of depression in adolescents, with a particular focus on
      pharmacological and psychological treatments as well as community and internet
      based prevention and treatment programmes. RECENT FINDINGS: The tendency for
      depression in young people to be associated with a number of other disorders and
      behaviours, including anxiety, suicide, conduct disorder and substance abuse,
      compounds the complexity of management and can contribute to a negative long-term
      impact on adult mental health. Results of recent randomized controlled trials
      have reinforced our understanding that the management of moderate-to-severe
      depression in adolescents should be assertive and prompt, typically including a
      combination of psychological and pharmacological interventions. SUMMARY: While
      the development of novel treatments is evolving, there is an urgent need to focus
      on defining the optimal use of available therapies and tailoring these to
      individual presentations, as well as upon improving identification of adolescent
      depressive disorders in the community.

PMID- 22156933
TI  - Melancholia.
AB  - PURPOSE OF REVIEW: The key question for melancholia is whether it should have
      status as a separate disorder and the literature of the last 12-24 months is
      surveyed largely from that perspective. RECENT FINDINGS: A number of interesting
      findings have appeared across a broad range of issues, but, with the possible
      exception of some large clinical trials, remain largely unreplicated. SUMMARY:
      Supporters of melancholia as a distinct entity will find little comfort in the
      recent literature.

PMID- 22156934
TI  - The 'true' prevalence of bipolar II disorder.
AB  - PURPOSE OF REVIEW: Many studies - including meta-analyses - do not distinguish
      between bipolar I and II disorder. The aim of this study is to review the recent
      literature on the prevalence, correlates, consequences, and treatment patterns of
      bipolar II disorder. RECENT FINDINGS: In the past 2 years, several important
      studies have been conducted in the bipolar II field. The World Mental Health
      Survey initiative provides us with prevalence rate across 11 countries, while
      several meta-analyses on suicide and neurocognition directly compared bipolar I
      with bipolar II, informing us on the severe consequences of bipolar II disorder.
      Results from studies showed that the lifetime prevalence rate of bipolar II
      disorder in adults across 11 countries was 0.4%. Rates of bipolar II disorder in
      prospective studies of adolescents are substantially greater, with lifetime rates
      approaching 3-4%. SUMMARY: Evidence from these studies regarding comparable
      clinical consequences, patterns of comorbidity, suicide attempts, family history,
      and treatment patterns to bipolar I disorder document the validity of the bipolar
      II subtype.

PMID- 22156935
TI  - Current status of knowledge on public-speaking anxiety.
AB  - PURPOSE OF REVIEW: This review examines the current knowledge on public-speaking
      anxiety, that is, the fear of speaking in front of others. This article
      summarizes the findings from previous review articles and describes new research
      findings on basic science aspects, prevalence rates, classification, and
      treatment that have been published between August 2008 and August 2011. RECENT
      FINDINGS: Recent findings highlight the major aspects of psychological and
      physiological reactivity to public speaking in individuals who are afraid to
      speak in front of others, confirm high prevalence rates of the disorder,
      contribute to identifying the disorder as a possibly distinct subtype of social
      anxiety disorder (SAD), and give support to the efficacy of treatment programs
      using virtual reality exposure and Internet-based self-help. SUMMARY: Public
      speaking anxiety is a highly prevalent disorder, leading to excessive
      psychological and physiological reactivity. It is present in a majority of
      individuals with SAD and there is substantial evidence that it may be a distinct
      subtype of SAD. It is amenable to treatment including, in particular, new
      technologies such as exposure to virtual environments and the use of cognitive
      behavioral self-help programs delivered on the Internet.

PMID- 22156936
TI  - Personality disorder and criminal behaviour:  what is the nature of the
      relationship?
AB  - PURPOSE OF REVIEW: There is a well established association between personality
      disorder and offending but the nature of the relationship is less well
      understood. We reviewed the recent literature on personality disorder and
      offending, picking out studies that examined the relationship between the two.
      RECENT FINDINGS: Cluster A, B and C personality disorders are each associated
      with different types of offences. Although rates of personality disorder are high
      in all serious offenders, the role played by personality disorder may be greater
      in some offences than others, for example, in rapists compared with child
      molesters, men who kill their fathers rather than their mothers, men who kill
      their children compared with mothers who kill their children; and in less severe
      stalking behaviour compared with those who get convictions. Three articles
      suggested frameworks for understanding how personality disorder may interact with
      other factors to contribute to offending. SUMMARY: Frameworks that integrate
      personality traits; comorbid problems such as substance misuse, mood disorders
      and attention deficit hyperactivity disorder (ADHD) symptoms; motivation for
      offending; maladaptive cognitions; beliefs and attitudes; anger and arousal; and
      situational factors are helpful when considering risk assessment, risk management
      and treatment. More empirical research is needed to test these theories.

PMID- 22156937
TI  - Recent trends in the treatment of prolonged grief.
AB  - PURPOSE OF REVIEW: Treatment for prolonged grief has been controversial. However,
      recent studies have clarified several key issues, offering important guidance to
      clinicians. This review summarizes the most recent evidence on the efficacy of
      grief treatments, moderators of treatment response, and new treatment approaches.
      RECENT FINDINGS: Recent research findings highlight that grief therapy is
      efficacious when targeted to adult and child grievers with persistent and
      elevated levels of distress. However, when grief therapy is applied as a
      universal intervention, it has minimal to no benefits, either for adults or for
      children. Earlier intervention for children is associated with greater efficacy.
      In recent studies, therapies employing cognitive-behavioral techniques, such as
      cognitive restructuring and exposure, have shown particularly robust effects in
      ameliorating grief symptoms. Other intervention approaches, including
      pharmacotherapy, internet-based, family-based, and preventive, have shown initial
      promise, but insufficient data exist to validate their efficacy to date. SUMMARY:
      Prolonged grief, a pattern of persistent and elevated distress following a loss,
      is increasingly recognized as an independent form of psychopathology that is
      responsive to treatment. Therapies that employ cognitive-behavioral techniques
      are efficacious in ameliorating the symptoms of prolonged grief and should be
      more widely used. However, grief therapy should not be deployed as a blanket
      intervention for all grievers. Antidepressant medication may serve a useful
      adjunctive role in grief therapy completion and in reducing bereavement-related
      depression.

PMID- 22156938
TI  - Current animal models of anxiety, anxiety disorders, and anxiolytic drugs.
AB  - PURPOSE OF REVIEW: The perception that 'classical' anxiety tests are deficient
      was formulated in the mid-1990s. Recent clinical trials also demonstrate that the
      predictive power of such tests is low, which emphasizes the need for developing
      models of higher translational value. Several novel models are proposed each
      year. Here, we investigate their impact on anxiolytic-related studies performed
      in 2010 and 2011. RECENT FINDINGS: Here, we depict as 'classical' all the tests
      that were developed at the same time as or earlier than the elevated plus-maze
      test. No test equaled its success in the subsequent decades; therefore, we
      consider it the endpoint of the period when the methodological bases of current
      laboratory research were laid down. Fourteen classical tests were employed in the
      investigated period, which were used in more than 80% of studies. Concurrently,
      36 'nonclassical' tests were used and six novel tests were also proposed. These
      accounted for fewer than 20% of studies. 'Classical' tests were often performed
      under unconventional conditions that putatively increased their translational
      value. Taken together, half of the studies involved at least one innovative step.
      Yet, the new procedures were infrequently used. Out of the 36 'nonclassical'
      tests, only 11 were used more than once, while the amendments to 'classical
      tests' were almost entirely laboratory specific. SUMMARY: Our analysis shows that
      there is a large interest in performing anxiety research innovatively. However,
      efforts are highly divergent and result in large numbers of poorly validated and
      infrequently used novel approaches. Thus, models with increased translational
      value still need to be developed.

PMID- 22156939
TI  - Comparative gene expression analysis between coronary arteries and internal
      mammary arteries identifies a role for the TES gene in endothelial cell functions
      relevant to coronary artery disease.
AB  - Coronary artery disease (CAD) is the leading cause of death worldwide. It has
      been established that internal mammary arteries (IMA) are resistant to the
      development of atherosclerosis, whereas left anterior descending (LAD) coronary
      arteries are athero-prone. The contrasting properties of these two arteries
      provide an innovative strategy to identify the genes that play important roles in
      the development of atherosclerosis. We carried out microarray analysis to
      identify genes differentially expressed between IMA and LAD. Twenty-nine genes
      showed significant differences in their expression levels between IMA and LAD,
      which included the TES gene encoding Testin. The role of TES in the
      cardiovascular system is unknown. Here we show that TES is involved in
      endothelial cell (EC) functions relevant to atherosclerosis. Western blot
      analysis showed higher TES expression in IMA than in LAD. Reverse transcription
      polymerase chain reaction and western blot analyses showed that TES was
      consistently and markedly down-regulated by more than 6-fold at both mRNA and
      protein levels in patients with CAD compared with controls without CAD (P=
      0.000049). The data suggest that reduced TES expression is associated with the
      development of CAD. Knockdown of TES expression by small-interfering RNA promoted
      oxidized-LDL-mediated monocyte adhesion to ECs, EC migration and the
      transendothelial migration of monocytes, while the over-expression of TES in ECs
      blunted these processes. These results demonstrate association between reduced
      TES expression and CAD, establish a novel role for TES in EC functions and raise
      the possibility that reduced TES expression increases susceptibility to the
      development of CAD.

PMID- 22156940
TI  - GM130 gain-of-function induces cell pathology in a model of lysosomal storage
      disease.
AB  - Cell pathology in lysosomal storage diseases is characterized by the formation of
      distended vacuoles with characteristics of lysosomes. Our previous studies in
      mucopolysaccharidosis type IIIB (MPSIIIB), a disease in which a genetic defect
      induces the accumulation of undigested heparan sulfate (HS) fragments, led to the
      hypothesis that abnormal lysosome formation was related to events occurring at
      the Golgi level. We reproduced the enzyme defect of MPSIIIB in HeLa cells using
      tetracycline-inducible expression of shRNAs directed against alpha-N
      acetylglucosaminidase (NAGLU) and addressed this hypothesis. HeLa cells deprived
      of NAGLU accumulated abnormal lysosomes. The Golgi matrix protein GM130 was over
      expressed. The cis- and medial-Golgi compartments were distended, elongated and
      formed circularized ribbons. The Golgi microtubule network was enlarged with
      increased amounts of AKAP450, a partner of GM130 controlling this network. GM130
      down-regulation prevented pathology in HeLa cells deprived of NAGLU, whereas
      GM130 over-expression in control HeLa cells mimicked the pathology of deprived
      cells. We concluded that abnormal lysosomes forming in cells accumulating HS
      fragments were the consequence of GM130 gain-of-function and subsequent
      alterations of the Golgi ribbon architecture. These results indicate that GM130
      functions are modulated by HS glycosaminoglycans and therefore possibly
      controlled by extracellular cues.

PMID- 22156941
TI  - An integrated ethical decision-making model for nurses.
AB  - The study reviewed 20 currently-available structured ethical decision-making
      models and developed an integrated model consisting of six steps with useful
      questions and tools that help better performance each step: (1) the
      identification of an ethical problem; (2) the collection of additional
      information to identify the problem and develop solutions; (3) the development of
      alternatives for analysis and comparison; (4) the selection of the best
      alternatives and justification; (5) the development of diverse, practical ways to
      implement ethical decisions and actions; and (6) the evaluation of effects and
      development of strategies to prevent a similar occurrence. From a pilot-test of
      the model, nursing students reported positive experiences, including being
      satisfied with having access to a comprehensive review process of the ethical
      aspects of decision making and becoming more confident in their decisions. There
      is a need for the model to be further tested and refined in both the educational
      and practical environments.

PMID- 22156942
TI  - Real-time control of angioplasty balloon inflation based on feedback from
      intravascular optical coherence tomography: preliminary study on an artery
      phantom.
AB  - A method is proposed to achieve computerized control of angioplasty balloon
      inflation, based on feedback from intravascular optical coherence tomography
      (IVOCT). Controlled balloon inflation could benefit clinical applications,
      cardiovascular research, and medical device industry. The proposed method was
      experimentally tested for balloon inflation within an artery phantom. During
      balloon inflation, luminal contour of the phantom was extracted from IVOCT images
      in real time. Luminal diameter was estimated from the obtained contour and was
      used in a feedback loop. Based on the estimated actual diameter and a target
      diameter, a computer controlled a programmable syringe pump to deliver or
      withdraw liquid in order to achieve the target diameter. The performance of the
      control method was investigated under different conditions, e.g., various flow
      rates and various target diameters. The results were satisfactory, as the control
      method provided convergence to the target diameters in various experiments.

PMID- 22156943
TI  - Multisensor data fusion for physical activity assessment.
AB  - This paper presents a sensor fusion method for assessing physical activity (PA)
      of human subjects, based on support vector machines (SVMs). Specifically,
      acceleration and ventilation measured by a wearable multisensor device on 50 test
      subjects performing 13 types of activities of varying intensities are analyzed,
      from which activity type and energy expenditure are derived. The results show
      that the method correctly recognized the 13 activity types 88.1% of the time,
      which is 12.3% higher than using a hip accelerometer alone. Also, the method
      predicted energy expenditure with a root mean square error of 0.42 METs, 22.2%
      lower than using a hip accelerometer alone. Furthermore, the fusion method was
      effective in reducing the subject-to-subject variability (standard deviation of
      recognition accuracies across subjects) in activity recognition, especially when
      data from the ventilation sensor were added to the fusion model. These results
      demonstrate that the multisensor fusion technique presented is more effective in
      identifying activity type and energy expenditure than the traditional
      accelerometer-alone-based methods.

PMID- 22156944
TI  - Automated algorithm for generalized tonic-clonic epileptic seizure onset
      detection based on sEMG zero-crossing rate.
AB  - Patients are not able to call for help during a generalized tonic-clonic
      epileptic seizure. Our objective was to develop a robust generic algorithm for
      automatic detection of tonic-clonic seizures, based on surface electromyography
      (sEMG) signals suitable for a portable device. Twenty-two seizures were analyzed
      from 11 consecutive patients. Our method is based on a high-pass filtering with a
      cutoff at 150 Hz, and monitoring a count of zero crossings with a hysteresis of
      +/-50 MUV . Based on data from one sEMG electrode (on the deltoid muscle), we
      achieved a sensitivity of 100% with a mean detection latency of 13.7 s, while the
      rate of false detection was limited to 1 false alarm per 24 h. The overall
      performance of the presented generic algorithm is adequate for clinical
      implementation.

PMID- 22156945
TI  - An implantable RF solenoid for magnetic resonance microscopy and
      microspectroscopy.
AB  - Miniature solenoids routinely enhance small volume nuclear magnetic resonance
      imaging and spectroscopy; however, no such techniques exist for patients. We
      present an implantable microcoil for diverse clinical applications, with a
      microliter coil volume. The design is loosely based on implantable depth
      electrodes, in which a flexible tube serves as the substrate, and a metal stylet
      is inserted into the tube during implantation. The goal is to provide enhanced
      signal-to-noise ratio (SNR) of structures that are not easily accessed by surface
      coils. The first-generation prototype was designed for implantation up to 2 cm,
      and provided initial proof-of-concept for microscopy. Subsequently, we optimized
      the design to minimize the influence of lead inductances, and to thereby double
      the length of the implantable depth (4 cm). The second-generation design
      represents an estimated SNR improvement of over 30% as compared to the original
      design when extended to 4 cm. Impedance measurements indicate that the device is
      stable for up to 24 h in body temperature saline. We evaluated the SNR and MR
      related heating of the device at 3T. The implantable microcoil can differentiate
      fat and water peaks, and resolve submillimeter features.

PMID- 22156946
TI  - Contributions of intrinsic visco-elastic torques during planar index finger and
      wrist movements.
AB  - Human hand movements have been studied for many decades, yet the role of hand
      biomechanics in achieving dexterity has not been fully understood. In this paper,
      we investigate the contributions of the intrinsic passive viscoelastic component
      in the hand during the coordinated wrist and hand movements. We compare the
      contributions of stiffness, damping, and dynamics torques under two types of
      joint phase movements at two speeds. The analysis of the data collected from
      subject studies demonstrated that the passive visco-elastic component is dominant
      over dynamic coupling terms. Although the exact contributions of the three
      torques vary under different speeds and phasic movements, the stiffness torque
      was the highest (at least 47%) followed by the damping torque, while the dynamics
      torque was the lowest (less than 11%) in all movement scenarios. Comparisons with
      studies involving coordinated arm movements illustrate that dominant torques in
      arm and hand movements are different suggesting that neural control strategies
      might be distinct as well.

PMID- 22156947
TI  - Nonlinear dynamic modeling of neuron action potential threshold during
      synaptically driven broadband intracellular activity.
AB  - Activity-dependent variation of neuronal thresholds for action potential (AP)
      generation is one of the key determinants of spike-train temporal-pattern
      transformations from presynaptic to postsynaptic spike trains. In this study, we
      model the nonlinear dynamics of the threshold variation during synaptically
      driven broadband intracellular activity. First, membrane potentials of single CA1
      pyramidal cells were recorded under physiologically plausible broadband
      stimulation conditions. Second, a method was developed to measure AP thresholds
      from the continuous recordings of membrane potentials. It involves measuring the
      turning points of APs by analyzing the third-order derivatives of the membrane
      potentials. Four stimulation paradigms with different temporal patterns were
      applied to validate this method by comparing the measured AP turning points and
      the actual AP thresholds estimated with varying stimulation intensities. Results
      show that the AP turning points provide consistent measurement of the AP
      thresholds, except for a constant offset. It indicates that 1) the variation of
      AP turning points represents the nonlinearities of threshold dynamics; and 2) an
      optimization of the constant offset is required to achieve accurate spike
      prediction. Third, a nonlinear dynamical third-order Volterra model was built to
      describe the relations between the threshold dynamics and the AP activities.
      Results show that the model can predict threshold accurately based on the
      preceding APs. Finally, the dynamic threshold model was integrated into a
      previously developed single neuron model and resulted in a 33% improvement in
      spike prediction.

PMID- 22156948
TI  - Instantaneous measure of EEG channel importance for improved patient-adaptive
      neonatal seizure detection.
AB  - A measure of bipolar channel importance is proposed for EEG-based detection of
      neonatal seizures. The channel weights are computed based on the integrated
      synchrony of classifier probabilistic outputs for the channels which share a
      common electrode. These estimated time-varying weights are introduced within a
      Bayesian probabilistic framework to provide a channel specific and, thus,
      adaptive seizure classification scheme. Validation results on a clinical dataset
      of neonatal seizures confirm the utility of the proposed channel weighting for
      the two patient-independent seizure detectors recently developed by this research
      group: one based on support vector machines (SVMs) and the other on Gaussian
      mixture models (GMMs). By exploiting the channel weighting, the receiver
      operating characteristic (ROC) area can be significantly increased for the most
      difficult patients, with the average ROC area across 17 patients increased by 22%
      (relative) for the SVM and by 15% (relative) for the GMM-based detector,
      respectively. It is shown that the system developed here outperforms the recent
      published studies in this area.

PMID- 22156949
TI  - The tinnitus functional index:  development of a new clinical measure for
      chronic, intrusive tinnitus.
AB  - OBJECTIVES: Chronic subjective tinnitus is a prevalent condition that causes
      significant distress to millions of Americans. Effective tinnitus treatments are
      urgently needed, but evaluating them is hampered by the lack of standardized
      measures that are validated for both intake assessment and evaluation of
      treatment outcomes. This work was designed to develop a new self-report
      questionnaire, the Tinnitus Functional Index (TFI), that would have documented
      validity both for scaling the severity and negative impact of tinnitus for use in
      intake assessment and for measuring treatment-related changes in tinnitus
      (responsiveness) and that would provide comprehensive coverage of multiple
      tinnitus severity domains. DESIGN: To use preexisting knowledge concerning
      tinnitus-related problems, an Item Selection Panel (17 expert judges) surveyed
      the content (175 items) of nine widely used tinnitus questionnaires. From those
      items, the Panel identified 13 separate domains of tinnitus distress and selected
      70 items most likely to be responsive to treatment effects. Eliminating redundant
      items while retaining good content validity and adding new items to achieve the
      recommended minimum of 3 to 4 items per domain yielded 43 items, which were then
      used for constructing TFI Prototype 1.Prototype 1 was tested at five clinics. The
      326 participants included consecutive patients receiving tinnitus treatment who
      provided informed consent-constituting a convenience sample. Construct validity
      of Prototype 1 as an outcome measure was evaluated by measuring responsiveness of
      the overall scale and its individual items at 3 and 6 mo follow-up with 65 and 42
      participants, respectively. Using a predetermined list of criteria, the 30 best
      functioning items were selected for constructing TFI Prototype 2.Prototype 2 was
      tested at four clinics with 347 participants, including 155 and 86 who provided 3
      and 6 mo follow-up data, respectively. Analyses were the same as for Prototype 1.
      Results were used to select the 25 best-functioning items for the final TFI.
      RESULTS: Both prototypes and the final TFI displayed strong measurement
      properties, with few missing data, high validity for scaling of tinnitus
      severity, and good reliability. All TFI versions exhibited the same eight factors
      characterizing tinnitus severity and negative impact. Responsiveness, evaluated
      by computing effect sizes for responses at follow-up, was satisfactory in all TFI
      versions.In the final TFI, Cronbach's alpha was 0.97 and test-retest reliability
      0.78. Convergent validity (r = 0.86 with Tinnitus Handicap Inventory [THI]; r =
      0.75 with Visual Analog Scale [VAS]) and discriminant validity (r = 0.56 with
      Beck Depression Inventory-Primary Care [BDI-PC]) were good. The final TFI was
      successful at detecting improvement from the initial clinic visit to 3 mo with
      moderate to large effect sizes and from initial to 6 mo with large effect sizes.
      Effect sizes for the TFI were generally larger than those obtained for the VAS
      and THI. After careful evaluation, a 13-point reduction was considered a
      preliminary criterion for meaningful reduction in TFI outcome scores.
      CONCLUSIONS: The TFI should be useful in both clinical and research settings
      because of its responsiveness to treatment-related change, validity for scaling
      the overall severity of tinnitus, and comprehensive coverage of multiple domains
      of tinnitus severity.

PMID- 22156950
TI  - Newly found interest--community health workers (CHWs).

PMID- 22156951
TI  - Policy barriers to health care access fuel discriminatory treatment: the role of
      Promotoras in overcoming malos tratos.
AB  - This article demonstrates that policy barriers resulting in access to health care
      inequities were significantly decreased by 2 Promotora interventions for 416
      legal and undocumented Latino immigrants in the California Central Valley.
      Promotoras conducted baseline/follow-up assessments and referrals/phone
      calls/visits during a 3-month period. In-depth interviews with Promotoras and a
      policy analysis on policy-driven access programs were carried out. Access to care
      was significantly increased between legal and undocumented immigrant from
      baseline to follow-up. Systemic barriers to access (malos tratos) reflected on
      personal barriers such as affordability of care. Promotoras help participants
      overcome barriers but do not change the policies determining access and
      procedures.

PMID- 22156952
TI  - Community health workers assisting patients with diabetes in self-management.
AB  - Community health workers (CHWs) have gained prominence in health care,
      recognizing the influence of community and environment on health. This study
      evaluates CHWs' efforts to assess patients' readiness to change and facilitate
      self-management goal setting. Six pairs of community health centers were randomly
      assigned to employ CHWs on health care teams. Each team worked with a defined
      population of patients. We assessed changes in documented patient self-management
      goals and clinical measures from both control and intervention CHCs before and
      after deploying CHWs, finding a significant increase in self-management goal
      setting between the intervention and control health centers.

PMID- 22156953
TI  - Care guides: employing nonclinical laypersons to help primary care teams manage
      chronic disease.
AB  - Lay persons ("care guides") without previous clinical experience were hired by a
      primary care clinic, trained for 2 weeks, and assigned to help 332 patients and
      their providers manage their diabetes, hypertension, and congestive heart
      failure. One year later, failure by these patients to meet nationally recommended
      guidelines was reduced by 28%, P < .001. Improvement was seen in tobacco usage,
      blood pressure control, pneumonia vaccination, low-density lipoprotein
      cholesterol levels, annual eye examinations, aspirin use, and microalbuminuria
      testing. Care guides served an average of 111 patients at an annual per patient
      cost of $392. Further testing of this model is warranted.

PMID- 22156954
TI  - Feasibility of chronic disease patient navigation in an urban primary care
      practice.
AB  - The purpose of this study was to evaluate the feasibility of incorporating
      chronic disease navigation using lay health care workers trained in motivational
      interviewing (MI) into an existing mammography navigation program. Primary-care
      patient navigators implemented MI-based telephone conversations around
      mammography, smoking, depression, and obesity. We conducted a small-scale
      demonstration, using mixed methods to assess patient outcomes and provider
      satisfaction. One hundred nine patients participated. Ninety-four percent
      scheduled and 73% completed a mammography appointment. Seventy-one percent agreed
      to schedule a primary care appointment and 54% completed that appointment.
      Patients and providers responded positively. Incorporating telephone-based
      chronic disease navigation supported by MI into existing disease-specific
      navigation is efficacious and acceptable to those enrolled.

PMID- 22156955
TI  - Cost savings associated with the use of community health centers.
AB  - This study assesses the potential cost savings associated with the use of
      community health centers, based on econometric analyses of the 2006 Medical
      Expenditure Panel Survey. After controlling for health status, health insurance
      coverage, income, age, and other factors, this study finds that patients who
      receive a majority of their ambulatory care at community health centers have
      significantly lower annual overall medical expenditures (24%) and ambulatory
      expenditures (25%) than those who do not. These results are consistent with other
      studies indicating that, by providing good quality primary care, community health
      centers can reduce the utilization of other medical services.

PMID- 22156956
TI  - US primary care delivery after the Health Center Growth Initiative: comparison of
      health centers, hospital outpatient departments, and physicians' offices.
AB  - We compared patient management during primary care visits in 3 settings (health
      centers, hospital outpatient departments, and physicians' offices) and
      investigated racial/ethnic and insurance-based disparities in the wake of the
      recent health center program expansion. Within health centers, there were few
      differences in patient management across racial/ethnic or insurance groups. In
      contrast, the other settings displayed more racial/ethnic and insurance
      disparities in patient management during visits. Health centers performed
      processes of care with comparable or higher occurrence, relative to physicians'
      offices. Health care disparities were also attenuated in health centers, compared
      with other primary care settings.

PMID- 22156958
TI  - Standards of care for occupational asthma: an update.
AB  - BACKGROUND: The British Thoracic Society (BTS) Standards of Care (SoC) Committee
      produced a standard of care for occupational asthma (OA) in 2008, based on a
      systematic evidence review performed in 2004 by the British Occupational Health
      Research Foundation (BOHRF). METHODS: BOHRF updated the evidence base from 2004
      2009 in 2010. RESULTS: This article summarises the changes in evidence and is
      aimed at physicians, nurses and other healthcare professionals in primary and
      secondary care, occupational health and public health and at employers, workers
      and their health, safety and other representatives. CONCLUSIONS: Various
      recommendations and evidence ratings have changed in the management of asthma
      that may have an occupational cause.

PMID- 22156959
TI  - Selective inhibition of intra-alveolar p55 TNF receptor attenuates ventilator
      induced lung injury.
AB  - BACKGROUND: Tumour necrosis factor (TNF) is upregulated in the alveolar space
      early in the course of ventilator-induced lung injury (VILI). Studies in
      genetically modified mice indicate that the two TNF receptors play opposing roles
      during injurious high-stretch mechanical ventilation, with p55 promoting but p75
      preventing pulmonary oedema. AIM: To investigate the effects of selective
      inhibition of intra-alveolar p55 TNF receptor on pulmonary oedema and
      inflammation during ventilator-induced lung injury using a newly developed domain
      antibody. METHODS: Anaesthetised mice were ventilated with high tidal volume and
      given an intratracheal bolus of p55-specific domain antibody or anti-TNF
      monoclonal antibody ('pure' VILI model). As a model of enhanced inflammation, a
      subclinical dose of lipopolysaccharide (LPS) was included in the intratracheal
      antibody bolus (LPS+VILI model). Development of lung injury was assessed by
      respiratory mechanics and blood gases and protein levels in lavage fluid. Flow
      cytometry was used to determine leucocyte recruitment and alveolar macrophage
      activation, while lavage fluid cytokines were assessed by ELISA. RESULTS: The
      ventilation protocol produced deteriorations in respiratory mechanics and gas
      exchange with increased lavage fluid protein levels in the two models. The p55
      specific domain antibody substantially attenuated all of these changes in the
      'pure' VILI model, while anti-TNF antibody was ineffective. In the LPS+VILI
      model, p55 blockade prevented deteriorations in respiratory mechanics and
      oxygenation and significantly decreased neutrophil recruitment, expression of
      intercellular adhesion molecule 1 on alveolar macrophages, and interleukin 6 and
      monocyte chemotactic protein 1 levels in lavage fluid. CONCLUSIONS: Selective
      inhibition of intra-alveolar p55 TNF receptor signalling by domain antibodies may
      open new therapeutic approaches for ventilated patients with acute lung injury.

PMID- 22156960
TI  - Coarse and fine particles but not ultrafine particles in urban air trigger
      hospital admission for asthma in children.
AB  - BACKGROUND: Short-term exposure to air pollution can trigger hospital admissions
      for asthma in children, but it is not known which components of air pollution are
      most important. There are no available studies on the particular effect of
      ultrafine particles (UFPs) on paediatric admissions for asthma. AIM: To study
      whether short-term exposure to air pollution is associated with hospital
      admissions for asthma in children. It is hypothesised that (1) the association
      between asthma admissions and air pollution is stronger with UFPs than with
      coarse (PM10) and fine (PM2.5) particles, nitrogen oxides (NOx) or nitrogen
      dioxide (NO2); and (2) infants are more susceptible to the effects of exposure to
      air pollution than older children. METHOD: Daily counts of admissions for asthma
      in children aged 0-18 years to hospitals located within a 15 km radius of the
      central fixed background urban air pollution measurement station in Copenhagen
      between 2001 and 2008 were extracted from the Danish National Patient Registry. A
      time-stratified case crossover design was applied and data were analysed using
      conditional logistic regression to estimate the effect of air pollution on asthma
      admissions. RESULTS: A significant association was found between hospital
      admissions for asthma in children aged 0-18 years and NOx (OR 1.11; 95% CI 1.05
      to 1.17), NO2 (1.10; 95% CI 1.04 to 1.16), PM10 (1.07; 95% CI 1.03 to 1.12) and
      PM2.5 (1.09; 95% CI 1.04 to 1.13); there was no association with UFPs. The
      association was stronger in infants than in older children for all pollutants,
      but no statistically significant interaction was detected. CONCLUSION: Short-term
      exposure to air pollution can trigger hospital admission for asthma in children,
      with infants possibly being most susceptible. These effects seemed to be mediated
      by larger particles and traffic-related gases, whereas UFPs showed no effect.

PMID- 22156961
TI  - Pharmacokinetics and short-term safety and tolerability of etravirine in
      treatment-experienced HIV-1-infected children and adolescents.
AB  - OBJECTIVES: To evaluate the pharmacokinetics, weight-based dose selection and
      short-term safety and tolerability of etravirine in HIV-1-infected children and
      adolescents. DESIGN: Phase I, nonrandomized, open-label study in two stages.
      METHODS: Children and adolescents aged at least 6 years to 17 years or less on a
      stable lopinavir/ritonavir-based antiretroviral regimen with HIV-1 RNA plasma
      viral load less than 50 copies/ml were enrolled. In both stages, etravirine (4
      mg/kg twice daily in stage I, 5.2 mg/kg twice daily in stage II), added to the
      existing antiretroviral regimen, was administered for 7 days followed by a
      morning dose and 12-h pharmacokinetic assessment on day 8. Pharmacokinetic
      parameters were determined using noncompartmental analysis. Data were compared
      with those previously established in HIV-1-infected adults on a similar
      etravirine (200 mg twice daily) combination antiretroviral regimen. RESULTS:
      Twenty-one patients were recruited to each stage; 19 and 20 had evaluable
      pharmacokinetics in stages I and II, respectively. Mean (SD) maximum plasma
      concentrations in stages I and II were 495 (453) and 757 ng/ml (680),
      respectively; area under the plasma concentration-time curve over 12 h was 4050
      (3602) and 6141 ng h/ml (5586), respectively. Statistical/qualitative comparisons
      showed comparable exposures with adults in stage II; however, the upper 90%
      confidence interval fell outside the predefined range. Plasma viral load remained
      undetectable on day 8 in all patients, and etravirine was well tolerated at both
      doses. CONCLUSION: Etravirine 5.2 mg/kg was well tolerated in this study and this
      dose was selected for further investigation in clinical trials.

PMID- 22156962
TI  - Perinatal outcomes, mitochondrial toxicity and apoptosis in HIV-treated pregnant
      women and in-utero-exposed newborn.
AB  - OBJECTIVE: Highly active antiretroviral therapy (HAART) has decreased the risk of
      HIV mother-to-child transmission. However, HIV and HAART have been associated
      with adverse perinatal outcome. HAART has been associated with mitochondrial
      dysfunction in nonpregnant adults, and HIV, additionally, to apoptosis. We
      determined whether mitochondrial toxicity and apoptosis are present in HIV
      pregnant women and their newborns and could be the basis of adverse pregnancy
      outcome. DESIGN: Single-site, cross-sectional, controlled observational study
      without intervention. METHODS: We studied mitochondrial and apoptotic parameters
      in mononuclear cells from maternal peripheral blood and infant cord blood at
      delivery in 27 HIV-infected and treated pregnant women, and 35 uninfected
      controls and their infants, to correlate clinical outcome with experimental
      findings: mitochondrial number (CS), mtDNA content (ND2/18SrRNA), mitochondrial
      protein synthesis (COX-II/V-DAC), mitochondrial function (enzymatic activities)
      and apoptotic rate (caspase-3/beta-actin). RESULTS: Global adverse perinatal
      outcome, preterm births and small newborn for gestational age were significantly
      increased in HIV pregnancies [odds ratio (OR) 7.33, 5.77 and 9.71]. Mitochondrial
      number was unaltered. The remaining mitochondrial parameters were reduced in HIV
      mothers and their newborn; especially newborn mtDNA levels, maternal and fetal
      mitochondrial protein synthesis and maternal glycerol-3-phosphate + complex III
      function (38.6, 25.8, 13.6 and 31.2% reduced, respectively, P < 0.05). All
      materno-fetal mitochondrial parameters significantly correlated, except mtDNA
      content. Apoptosis was exclusively increased in infected pregnant women, but not
      in their newborn. However, adverse perinatal outcome did not correlate
      mitochondrial or apoptotic findings. CONCLUSIONS: Transplacental HAART toxicity
      may cause subclinical mitochondrial damage in HIV-pregnant women and their
      newborn. Trends to increased maternal apoptosis may be due to maternal-restricted
      HIV infection. However, we could not demonstrate mitochondrial or apoptotic
      implication in adverse perinatal outcome.

PMID- 22156963
TI  - High HIV incidence among MSM prescribed postexposure prophylaxis, 2000-2009: 
      indications for ongoing sexual risk behaviour.
AB  - OBJECTIVE: To determine (trends in) HIV incidence among MSM? who have recently
      had postexposure prophylaxis (PEP) prescribed in Amsterdam, compared with MSM
      participating in the Amsterdam Cohort Studies (ACS). DESIGN AND METHODS: We used
      data from MSM who were prescribed PEP in Amsterdam between 2000 and 2009, who
      were HIV-negative at the time of PEP prescription and had follow-up HIV testing 3
      and/or 6 months after PEP prescription (n = 395). For comparison, cohort data
      from MSM participating in the ACS in the same period were used (n = 782). Poisson
      log-linear regression analyses were performed to model trends in HIV incidence
      and identify differences in HIV incidence between both cohorts at different time
      points. RESULTS: Between 2000 and 2009, among MSM who were prescribed PEP, an
      overall HIV incidence of 6.4 [95% confidence interval (CI) 3.4-11.2] per 100
      person-years was found, compared with an HIV incidence of 1.6 (95% CI 1.3-2.1)
      per 100 person-years among MSM participating in the ACS (P < 0.01). In both
      cohorts, an increasing trend in HIV incidence over time was observed [incidence
      rate ratio (IRR(per calendar year)) 1.3 (95% CI 0.9-1.7) and 1.1 (95% CI 1.0-1.2)
      among MSM prescribed PEP and MSM of the ACS, respectively]. The difference in HIV
      incidence between both cohorts was most evident in more recent years [IRR(PEP
      versus ACS in 2009) 4.8 (95% CI 2.0-11.5)]. CONCLUSION: Particularly in more
      recent years, MSM recently prescribed PEP had a higher HIV incidence compared
      with MSM participating in the ACS, indicating ongoing sexual risk behaviour.

PMID- 22156964
TI  - Vitamin D deficiency and persistent proteinuria among HIV-infected and uninfected
      injection drug users.
AB  - OBJECTIVE: Proteinuria occurs commonly among HIV-infected and uninfected
      injection drug users (IDUs) and is associated with increased mortality risk.
      Vitamin D deficiency, highly prevalent among IDUs and potentially modifiable, may
      contribute to proteinuria. To determine whether vitamin D is associated with
      proteinuria in this population, we conducted a cross-sectional study in the AIDS
      Linked to the IntraVenous Experience (ALIVE) Study. METHODS: 25(OH)-vitamin D
      levels were measured in 268 HIV-infected and 614 HIV-uninfected participants. The
      association between vitamin D deficiency (<10  ng/ml) and urinary protein
      excretion was evaluated by linear regression. The odds of persistent proteinuria
      (urine protein-to-creatinine ratio >200  mg/g on two occasions) associated with
      vitamin D deficiency was examined using logistic regression. RESULTS: One-third
      of participants were vitamin D-deficient. Vitamin D deficiency was independently
      associated with higher urinary protein excretion (P < 0.05) among HIV-infected
      and diabetic IDUs (P-interaction < 0.05 for all). Persistent proteinuria occurred
      in 18% of participants. Vitamin D deficiency was associated with greater than six
      fold odds of persistent proteinuria among diabetic IDUs [odds ratio (OR) 6.29,
      95% confidence interval (CI) 1.54, 25.69] independent of sociodemographic
      characteristics, comorbid conditions, body mass index, and impaired kidney
      function [estimated glomerular filtration rate (eGFR) <60  ml/min per 1.73 
      m(2)]; no association, however, was observed among nondiabetic IDUs (OR 1.06, 95%
      CI 0.64, 1.76) (P-interaction <0.05). CONCLUSIONS: Vitamin D deficiency was
      associated with higher urinary protein excretion among those with HIV infection
      and diabetes. Vitamin D deficiency was independently associated with persistent
      proteinuria among diabetic IDUs, although not in nondiabetic persons. Whether
      vitamin D repletion ameliorates proteinuria in these patients requires further
      study.

PMID- 22156965
TI  - mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses
      in HIV-1-infected patients.
AB  - BACKGROUND: In an effort to raise protective antiviral immunity, dendritic cell
      immunotherapy was evaluated in six adults infected with human immunodeficiency
      virus (HIV)-1 and stable under highly active antiretroviral therapy (HAART).
      DESIGN AND METHODS: Autologous monocyte-derived dendritic cells electroporated
      with mRNA encoding Gag and a chimeric Tat-Rev-Nef protein were administered,
      whereas patients remained on HAART. Feasibility, safety, immunogenicity and
      antiviral responses were investigated. RESULTS: Dendritic cell vaccine
      preparation and administration were successful in all patients and only mild
      adverse events were seen. There was a significant increase post-dendritic cell as
      compared to pre-dendritic cell vaccination in magnitude and breadth of HIV-1
      specific interferon (IFN)-gamma response, in particular to Gag, and in T-cell
      proliferation. Breadth of IFN-gamma response and T-cell proliferation were both
      correlated with CD4(+) and CD8(+) polyfunctional T-cell responses. Importantly,
      dendritic cell vaccination induced or increased the capacity of autologous CD8(+)
      T cells to inhibit superinfection of CD4(+) T cells with the vaccine-related IIIB
      virus and some but not all other HIV-1 strains tested. This HIV-1-inhibitory
      activity, indicative of improved antiviral response, was correlated with
      magnitude and breadth of Gag-specific IFN-gamma response. CONCLUSIONS:
      Therapeutic immunization with dendritic cells was safe and successful in raising
      antiviral cellular immune responses, including effector CD8(+) T cells with virus
      inhibitory activity. The stimulation of those potent immunological and antiviral
      effects, which have been associated with control of HIV-1, underscores the
      potential of dendritic cell vaccination in the treatment of HIV-1. The incomplete
      nature of the response in some patients helped to identify potential targets for
      future improvement, that is increasing antigenic spectrum and enhancing T-cell
      response.

PMID- 22156966
TI  - Contraceptive method and pregnancy incidence among women in HIV-1-serodiscordant
      partnerships.
AB  - BACKGROUND: Effective contraception reduces unintended pregnancies and is a
      central strategy to reduce vertical HIV-1 transmission for HIV-1-infected women.
      METHODS: Among 2269 HIV-1-seropositive and 1085-seronegative women from seven
      African countries who were members of HIV-1-serodiscordant heterosexual
      partnerships and who were participating in an HIV-1 prevention clinical trial, we
      assessed pregnancy incidence according to contraceptive method using multivariate
      Andersen-Gill analysis. RESULTS: Compared with women using no contraceptive
      method, pregnancy incidence was significantly reduced among HIV-1-seropositive
      and HIV-1-seronegative women using injectable contraception [adjusted hazard
      ratio (aHR) 0.24, P = 0.001 and aHR 0.25, P < 0.001, respectively). Oral
      contraceptives significantly reduced pregnancy risk only among HIV-1-seropositive
      women (aHR 0.51, P = 0.004) but not seronegative women (aHR 0.64, P = 0.3), and,
      for both seropositive and seronegative women, oral contraceptive pill users were
      more likely to become pregnant than injectable contraceptive users (aHR 2.22, P =
      0.01 for HIV-1-seropositive women and aHR 2.65, P = 0.09 for HIV-1-seronegative
      women). Condoms, when reported as being used as the primary contraceptive method,
      marginally reduced pregnancy incidence (aHR 0.85, P = 0.1 for seropositive women
      and aHR 0.67, P = 0.02 for seronegative women). There were no pregnancies among
      women using intrauterine devices, implantable methods or who had undergone
      surgical sterilization, although these methods were used relatively infrequently.
      CONCLUSION: Family planning programs and HIV-1 prevention trials need innovative
      ways to motivate uptake and sustained use of longer acting, less user-dependent
      contraception for women who do not desire pregnancy.

PMID- 22156967
TI  - A randomized trial of a behavioral intervention for black MSM:  the DiSH study.
AB  - OBJECTIVE: To test a new behavioral intervention for black MSM in reducing sexual
      risk and increasing social support and intentions to use condoms. DESIGN: A
      single-site, unblinded randomized trial in New York City with 3-month follow-up.
      METHODS: Participants (n = 283) reporting at least two sexual partners and
      unprotected anal intercourse with a man in the past 3 months were enrolled and
      randomized to a social-cognitive theory-based intervention or control comparison.
      Men in the intervention group participated in five 2-h group sessions focused on
      creating a group environment with sexual risk-reduction information and exercises
      woven into joint meal preparation and sharing activities, while exploring self
      efficacy perceptions and outcome expectancies. Intervention (n = 142) and control
      (n = 141) groups received standard HIV counseling and testing at baseline.
      RESULTS: No significant differences were found between study arms at 3 months in
      number of male partners, number of unprotected anal intercourse partners,
      proportion reporting unprotected sex, number of acts protected by condoms, self
      efficacy, condom attitudes, condom intentions, social isolation and psychological
      distress. In both arms combined, declines from baseline to 3 months were observed
      in sexual risk behaviors, social isolation and psychological distress, whereas
      self-efficacy, condom attitudes and condom intentions improved. CONCLUSION: As
      the HIV epidemic continues to have a dramatic impact on black MSM in the USA, the
      urgency to design innovative interventions continues.

PMID- 22156968
TI  - Predictors of weight loss after HAART initiation among HIV-infected adults in
      Tanzania.
AB  - OBJECTIVE: To explore the predictors of weight loss after highly active
      antiretroviral therapy (HAART) initiation in a large cohort of HIV-infected
      adults living in Dar es Salaam, Tanzania. DESIGN: Cross-sectional and
      longitudinal analysis of a cohort of HIV-infected adults on HAART. METHODS: HIV
      infected adults (n = 18 965) were enrolled between November 2004 to December 2009
      in Dar es Salaam, Tanzania. Log-binomial regression and Cox proportional hazard
      regression were used to explore the predictors of short-term (3 months) and long
      term significant weight loss (>= 5%) after HAART initiation. RESULTS: At 3 months
      after HAART initiation, 8% patients lost greater than or equal to 5% weight.
      Underweight patients at initiation gained more weight than other body mass index
      (BMI) groups. Younger or older than age group 30-39, lower socioeconomic status
      (SES), higher BMI, lower hemoglobin, difficulty breathing, loss of appetite,
      nausea/vomiting at baseline were associated with the risk of significant weight
      loss at 3 months after initiation. During a median follow-up period of 10 months
      [interquartile range (IQR) 4-20 months], 31% patients had experienced an initial
      significant weight loss after HAART initiation. In addition to time-varying CD4
      cell count and hemoglobin level, age, sex, baseline BMI and having loss of
      appetite, and nausea/vomiting at baseline were associated with the risk of long
      term significant weight loss. CONCLUSION: Our study suggested that a significant
      percentage of patients continue to lose weight after HAART initiation. Our
      findings on the effect of socio-demographics, symptoms and diseases, biomedical
      indicators in relation to weight loss provide important information that has
      significant practical implications.

PMID- 22156969
TI  - Altered dendritic cell-natural killer interaction in Kenyan sex workers resistant
      to HIV-1 infection.
AB  - BACKGROUND: Natural killer (NK) cells are members of the innate immune system
      that play an important role in the defense against viral infection. They are also
      involved in the regulation of adaptive immune responses through cytokine
      secretion and the interaction with antigen-presenting cells. However, their role
      in HIV infection is only partially understood. OBJECTIVE: Here we studied the
      phenotype and function of NK cells of highly HIV-exposed but seronegative (HESN)
      uninfected commercial sex workers from Kenya who can be epidemiologically defined
      as relatively resistant to HIV infection. DESIGN: The purpose of this study was
      to gain insight into the role of NK cells in mediating resistance to HIV-1. This
      information can be used to better understand protection from infection which can
      be used for informing future design of effective prophylactics and therapeutics
      for HIV. METHODS: Whole blood samples were collected from study participants and
      isolated NK cells and dendritic cells were used in assays for phenotyping and
      cell function. RESULTS: Activated NK cells from resistant women killed autologous
      immature dendritic cells more efficiently and also secreted more interferon (IFN)
      gamma than those of uninfected, susceptible women. Interestingly, NK cells from
      HIV-resistant women were significantly more effective in inducing secretion of IL
      12 in immature dendritic cells. CONCLUSIONS: These data suggest that an altered
      NK cell-dendritic cell interaction plays an important role in the protection from
      infection with HIV-1.

PMID- 22156970
TI  - The effects of injectable hormonal contraceptives on HIV seroconversion and on
      sexually transmitted infections.
AB  - OBJECTIVES: To investigate the association between hormonal contraceptives and
      risk of HIV-1 seroconversion and prevalence of other sexually transmitted
      infections. DESIGN: Prospective cohort. METHODS: The study population was 2,236
      HIV-negative women who were screened in a biomedical intervention trial in
      Durban, South Africa. The association between the use of hormonal contraceptives
      and risk of HIV-1 seroconversion was modeled using Cox proportional hazards
      regression analysis. Prevalence of Chlamydia trachomatis and Neisseria
      gonorrhoeae infections were assessed using logistic regression models. RESULTS:
      Hormonal injectables were the most common method of contraceptives (46.47%)
      followed by condom use (28.04%). Overall, compared with women who reported using
      condoms or other methods as their preferred form of contraceptive, those who
      reported using hormonal contraceptives (injectables and oral pills) were less
      likely to use condoms in their last sexual act. Using hormonal injectables during
      the study was significantly associated with increased risk for HIV-1 infection
      [adjusted hazard ratio 1.72, 95% confidence interval (CI) 1.19-2.49, P = 0.005];
      hormonal injectables were also significantly associated with higher prevalent of
      C. trachomatis infections (adjusted odds ratio 2.46, 95% CI 1.52-3.97, P <
      0.001). CONCLUSION: Hormonal injectables are highly effective and well tolerated
      family planning methods and have played an important role in reducing unplanned
      pregnancies and maternal and infant mortality. However, they do not protect
      against HIV-1 and other sexually transmitted infections. This study reinforces
      the importance of comprehensive contraceptive counseling to women about the
      importance of dual protection, such as male condoms and hormonal contraceptives
      use.

PMID- 22156971
TI  - Less decrease in risk behaviour from pre-HIV to post-HIV seroconversion among MSM
      in the combination antiretroviral therapy era compared with the pre-combination
      antiretroviral therapy era.
AB  - OBJECTIVE: To gain insight in the ongoing HIV transmission, we compared sexual
      risk behaviour pre-HIV and post-HIV seroconversion in 206 MSM participating in
      the Amsterdam Cohort Studies (1984-2008) before and after the introduction of
      combination antiretroviral therapy (cART). DESIGN AND METHODS: MSM completed
      behavioural questionnaires and were tested for HIV antibodies every 6 months.
      Trends in anal intercourse and number of sex partners from 4 years before HIV
      seroconversion until 4 years after diagnosis were analysed with latent class
      random effects logistic regression models. RESULTS: The risk of having
      unprotected anal intercourse (UAI) 1 year after HIV diagnosis decreased
      significantly when compared with 1 year before diagnosis in both the pre-cART era
      [difference, 30%; 95% confidence interval (CI), 22-36%] and cART era (difference,
      19%; 95% CI, 9-30%). In contrast to a continuing decrease of UAI in the pre-cART
      era, the probability of UAI in the cART era increased again to preseroconversion
      levels (61%; 95% CI, 48-74%)) 4 years after diagnosis. CONCLUSION: This study
      provides evidence that recently seroconverted MSM reduce their sexual risk
      behaviour following HIV diagnosis both in the pre-cART as well as the cART
      period. However, in the cART period this reduction in sexual risk behaviour is
      less and returns to pre-cART levels within 4 years. These findings not only
      confirm the need for early HIV testing but also make it clear that much more
      effort should go into identifying, counselling, and possibly treating recently
      seroconverted MSM who have been found to be one of the most important drivers of
      HIV transmission among MSM.

PMID- 22156972
TI  - Assessing mortality in women with hepatitis C virus and HIV using indirect
      markers of fibrosis.
AB  - OBJECTIVE: Co-infection with hepatitis C virus (HCV) is a major cause of
      morbidity and mortality in HIV-infected individuals. However, predictors of
      mortality are poorly defined and most studies have focused predominantly on co
      infection in men. We evaluated whether two indirect markers of hepatic fibrosis,
      aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 scores, were
      predictive of mortality in a well defined longitudinal cohort of HCV/HIV-co
      infected women on HAART. METHODS: HCV/HIV-co-infected women on antiretroviral
      therapy enrolled in Women's Interagency HIV Study (WIHS), a National Institutes
      of Health-funded prospective, multicenter, cohort study of women with and at risk
      for HIV infection were included. Using Cox regression analysis, associations
      between APRI and FIB-4 with all-cause mortality were assessed. RESULTS: Four
      hundred and fifty HCV/HIV-co-infected women, of whom 191 women died, had a median
      follow-up of 6.6 years and 5739 WIHS visits. Compared with women with low APRI or
      FIB-4 levels, severe fibrosis was significantly associated with an increased risk
      of all-cause mortality {APRI: hazard ratio 2.78 [95% confidence interval (CI)
      1.87, 4.12]; FIB-4: hazard ratio 2.58 (95% CI 1.68, 3.95)}. Crude death rates per
      1000 patient-years increased with increasing liver fibrosis: 34.8 for mild, 51.3
      for moderate and 167.9 for severe fibrosis as measured by FIB-4. Importantly,
      both APRI and FIB-4 increased during the 5 years prior to death for all women:
      the slope of increase was greater for women dying a liver-related death compared
      with nonliver-related death. CONCLUSION: Both APRI and FIB-4 are independently
      associated with all-cause mortality in HCV/HIV-co-infected women and may have
      clinical prognostic utility among women with HIV and HCV.

PMID- 22156973
TI  - Hormonal contraception and the risk of HIV acquisition among women in South
      Africa.
AB  - OBJECTIVES: To evaluate the effect of hormonal contraception including combined
      oral contraceptives (COCs), and the injectable progestins depo
      medroxyprogesterone acetate (DMPA) and norethisterone enanthate (Net-En) on the
      risk of HIV acquisition among women in South Africa. DESIGN/METHODS: We analyzed
      data from 5567 women aged 16-49 years participating in the Carraguard Phase 3
      Efficacy Trial. Participants were interviewed about contraceptive use and sexual
      behaviors and underwent pelvic examinations and HIV testing quarterly. We used
      marginal structural Cox regression models to estimate the effect of hormonal
      contraception exposure on HIV acquisition risk among women overall and among
      young women (16-24 years) in particular. RESULTS: Two hundred and seventy
      participants became HIV-infected (3.7 per 100 woman-years); HIV incidence was
      2.8, 4.6, 3.5 and 3.4 per 100 woman-years in the COC, DMPA, Net-En and
      nonhormonal contraceptive groups, respectively (P = 0.09). The adjusted hazard
      ratios (AHRs) were 0.84 [95% confidence interval (CI) 0.51-1.39], 1.28 (95% CI
      0.92-1.78) and 0.92 (95% CI 0.64-1.32) among COC, DMPA and Net-En users,
      respectively, compared with the nonhormonal group controlling for covariates. Age
      modified the effect of hormonal contraception on HIV acquisition risk; among
      young women, the AHRs were 1.02 (95% CI 0.46-2.28) for COCs, 1.68 (95% CI 0.96
      2.94) for DMPA and 1.36 (95% CI0.78-2.35) for Net-En users. CONCLUSIONS: In this
      study conducted among South African women, hormonal contraception did not
      significantly increase the risk of HIV acquisition. However, the effect estimate
      does not rule out a moderate increase in HIV risk associated with DMPA use found
      in some other recent studies.

PMID- 22156974
TI  - Retention in a public healthcare system with free access to treatment:  a Danish
      nationwide HIV cohort study.
AB  - OBJECTIVE: We aimed to assess retention of HIV-infected individuals in the Danish
      healthcare system over a 15-year period. METHODS: Loss to follow-up (LTFU) was
      defined as 365 days without contact to the HIV care system. Data were obtained
      from the nationwide Danish HIV Cohort study, The Danish National Hospital
      Registry and The Danish Civil Registration System. Incidence rates, risk factors
      for LTFU and return to care and mortality rate ratios (MRRs) were estimated using
      Poisson regression analyses. RESULTS: We included 4745 HIV patients who were
      followed for 36,692 person-years. Patients were retained in care 95.0% of person
      years under observation, increasing to 98.1% after initiation of highly active
      antiretroviral treatment (HAART). The overall incidence rate/100 person-years for
      first episode of LTFU was 2.6 [95% confidence interval (CI) 2.5-2.8] and was
      significantly lower after initiation of HAART [1.2 (95% CI 1.0-1.3)]. Five years
      after LTFU the probability of return to care was 0.87 (95% CI 0.84-0.90). The
      risk of death was significantly increased after LTFU [MRR 1.9 (95% CI 1.6-2.6)]
      and 6 months or less after return to care [MRR 10.9 (95% CI 5.9-19.9)].
      CONCLUSION: Retention in care of Danish HIV patients is high, especially after
      initiation of HAART. Absence from HIV care is associated with increased
      mortality. We conclude that high rates of retention can be achieved in a
      healthcare system with free access to treatment and is associated with a
      favorable outcome.

PMID- 22156975
TI  - Treatment as prevention:  some additional thoughts.

PMID- 22156976
TI  - The psychology of wound healing.
AB  - PURPOSE OF REVIEW: Research into the effects of psychological factors on wound
      healing represents an ideal research model for psychoneuroimmunology, as both the
      impact on clinically relevant health outcomes and the underlying biological
      mechanisms can be examined. Mounting interest in this topic from biological
      scientists, psychologists, and medical specialists has resulted in new findings
      that are discussed in this review. RECENT FINDINGS: Known psychological
      influences on wound healing include stress as well as coping styles, positive
      affect, environmental enrichment, and social support. Research has highlighted
      the roles of oxytocin, vasopressin, epinephrine, cortisol, and leukocyte
      redistribution in wound healing. Clinical significance has been demonstrated by a
      growing number of studies in patient populations. Furthermore, pragmatic
      interventions with clinical samples have demonstrated clear benefits of
      psychological interventions on wound healing. SUMMARY: Recent studies add to
      growing evidence that psychology impacts wound repair, and highlight in
      particular the positive role of social support on modulating the negative effects
      of stress. The first few studies to demonstrate that psychological interventions
      can improve healing in clinical populations are exciting developments. New
      knowledge of psychobiological mechanisms provides opportunities to develop
      further interventions to improve health outcomes.

PMID- 22156977
TI  - Fiducial optimization for minimal target registration error in image-guided
      neurosurgery.
AB  - This paper presents new methods for the optimal selection of anatomical landmarks
      and optimal placement of fiducial markers in image-guided neurosurgery. These
      methods allow the surgeon to optimally plan fiducial marker locations on routine
      diagnostic images before preoperative imaging and to intraoperatively select the
      set of fiducial markers and anatomical landmarks that minimize the expected
      target registration error (TRE). The optimization relies on a novel empirical
      simulation-based TRE estimation method built on actual fiducial localization
      error (FLE) data. Our methods take the guesswork out of the registration process
      and can reduce localization error without additional imaging and hardware. Our
      clinical experiments on five patients who underwent brain surgery with a
      navigation system show that optimizing one marker location and the anatomical
      landmarks configuration reduced the TRE. The average TRE values using the usual
      fiducials setup and using the suggested method were 4.7 mm and 3.2 mm,
      respectively. We observed a maximum improvement of 4 mm. Reducing the target
      registration error has the potential to support safer and more accurate minimally
      invasive neurosurgical procedures.

PMID- 22156978
TI  - Tracking monotonically advancing boundaries in image sequences using graph cuts
      and recursive kernel shape priors.
AB  - We introduce a probabilistic computer vision technique to track monotonically
      advancing boundaries of objects within image sequences. Our method incorporates a
      novel technique for including statistical prior shape information into graph-cut
      based segmentation, with the aid of a majorization-minimization algorithm.
      Extension of segmentation from single images to image sequences then follows
      naturally using sequential Bayesian estimation. Our methodology is applied to two
      unrelated sets of real biomedical imaging data, and a set of synthetic images.
      Our results are shown to be superior to manual segmentation.

PMID- 22156979
TI  - Diffeomorphic metric mapping of high angular resolution diffusion imaging based
      on Riemannian structure of orientation distribution functions.
AB  - In this paper, we propose a novel large deformation diffeomorphic registration
      algorithm to align high angular resolution diffusion images (HARDI) characterized
      by orientation distribution functions (ODFs). Our proposed algorithm seeks an
      optimal diffeomorphism of large deformation between two ODF fields in a spatial
      volume domain and at the same time, locally reorients an ODF in a manner such
      that it remains consistent with the surrounding anatomical structure. To this
      end, we first review the Riemannian manifold of ODFs. We then define the
      reorientation of an ODF when an affine transformation is applied and
      subsequently, define the diffeomorphic group action to be applied on the ODF
      based on this reorientation. We incorporate the Riemannian metric of ODFs for
      quantifying the similarity of two HARDI images into a variational problem defined
      under the large deformation diffeomorphic metric mapping framework. We finally
      derive the gradient of the cost function in both Riemannian spaces of
      diffeomorphisms and the ODFs, and present its numerical implementation. Both
      synthetic and real brain HARDI data are used to illustrate the performance of our
      registration algorithm.

PMID- 22156980
TI  - Use of needle track detection to quantify the displacement of stranded seeds
      following prostate brachytherapy.
AB  - We aim to compute the movement of permanent stranded implant brachytherapy
      radioactive sources (seeds) in the prostate from the planned seed distribution to
      the intraoperative fluoroscopic distribution, and then to the postimplant
      computed tomography (CT) distribution. We present a novel approach to matching
      the seeds in these distributions to the plan by grouping the seeds into needle
      tracks. First, we identify the implantation axis using a sample consensus
      algorithm. Then, we use a network flow algorithm to group seeds into their needle
      tracks. Finally, we match the needles from the three stages using both their
      transverse plane location and the number of seeds per needle. We validated our
      approach on eight clinical prostate brachytherapy cases, having a total of 871
      brachytherapy seeds distributed in 193 needles. For the intraoperative and
      postimplant data, 99.31% and 99.41% of the seeds were correctly assigned,
      respectively. For both the preplan to fluoroscopic and fluoroscopic to CT
      registrations, 100% of the needles were correctly matched. We show that there is
      an average intraoperative seed displacement of  4.94+/-2.42 mm  and a further 
      2.97+/-1.81 mm of postimplant movement. This information reveals several
      directional trends and can be used for quality control, treatment planning, and
      intraoperative dosimetry that fuses ultrasound and fluoroscopy.

PMID- 22156981
TI  - Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the
      first 1 million tests.
AB  - INTRODUCTION: The Bowel Cancer Screening Programme in England began operating in
      2006 with the aim of full roll out across England by December 2009. Subjects aged
      60-69 are being invited to complete three guaiac faecal occult blood tests (6
      windows) every 2 years. The programme aims to reduce mortality from colorectal
      cancer by 16% in those invited for screening. METHODS: All subjects eligible for
      screening in the National Health Service in England are included on one database,
      which is populated from National Health Service registration data covering about
      98% of the population of England. This analysis is only of subjects invited to
      participate in the first (prevalent) round of screening. RESULTS: By October 2008
      almost 2.1 million had been invited to participate, with tests being returned by
      49.6% of men and 54.4% of women invited. Uptake ranged between 55-60% across the
      four provincial hubs which administer the programme but was lower in the London
      hub (40%). Of the 1.08 million returning tests 2.5% of men and 1.5% of women had
      an abnormal test. 17,518 (10,608 M, 6910 F) underwent investigation, with 98%
      having a colonoscopy as their first investigation. Cancer (n=1772) and higher
      risk adenomas (n=6543) were found in 11.6% and 43% of men and 7.8% and 29% of
      women investigated, respectively. 71% of cancers were 'early' (10% polyp cancer,
      32% Dukes A, 30% Dukes B) and 77% were left-sided (29% rectal, 45% sigmoid) with
      only 14% being right-sided compared with expected figures of 67% and 24% for left
      and right side from UK cancer registration. CONCLUSION: In this first round of
      screening in England uptake and fecal occult blood test positivity was in line
      with that from the pilot and the original European trials. Although there was the
      expected improvement in cancer stage at diagnosis, the proportion with left-sided
      cancers was higher than expected.

PMID- 22156982
TI  - Arg77His and Trp187Arg are the most common mutations causing FXIII deficiency in
      Iran.
AB  - The aim of this study was to review the literature for the genetic mutations
      causing inherited factoe XIII (FXIII) deficiency in patients from Iran, where the
      consanguineous marriage is common. Data were collected from 30 patients (18 males
      and 12 females) with FXIII deficiency, from 26 unrelated families. Data of
      mutation analysis were obtained from 2 previously published studies. A total of 7
      mutations consisting of 5 new mutations and 2 previously reported mutations were
      identified. Of the 5 novel missense mutations, 2, Arg77His and Trp187Arg, were
      the most common in Iranian FXIII-deficient patients. In regions like Iran with
      high rate of consanguineous marriages, the identification of common mutations in
      disease like severe FXIII deficiency increases the capacity to make a precise
      screening and diagnosis assays to screen and diagnose families with high risk of
      FXIII deficiency for prevention of clinical complications in them.

PMID- 22156983
TI  - Neural network-based multiple robot simultaneous localization and mapping.
AB  - In this paper, a decentralized platform for simultaneous localization and mapping
      (SLAM) with multiple robots is developed. Each robot performs single robot view
      based SLAM using an extended Kalman filter to fuse data from two encoders and a
      laser ranger. To extend this approach to multiple robot SLAM, a novel occupancy
      grid map fusion algorithm is proposed. Map fusion is achieved through a multistep
      process that includes image preprocessing, map learning (clustering) using neural
      networks, relative orientation extraction using norm histogram cross correlation
      and a Radon transform, relative translation extraction using matching norm
      vectors, and then verification of the results. The proposed map learning method
      is a process based on the self-organizing map. In the learning phase, the
      obstacles of the map are learned by clustering the occupied cells of the map into
      clusters. The learning is an unsupervised process which can be done on the fly
      without any need to have output training patterns. The clusters represent the
      spatial form of the map and make further analyses of the map easier and faster.
      Also, clusters can be interpreted as features extracted from the occupancy grid
      map so the map fusion problem becomes a task of matching features. Results of the
      experiments from tests performed on a real environment with multiple robots prove
      the effectiveness of the proposed solution.

PMID- 22156984
TI  - Guest editorial: special section on data-based control, modeling, and
      optimization.

PMID- 22156986
TI  - Epstein-Barr virus in multiple sclerosis: a continuing conundrum.

PMID- 22156987
TI  - Association of innate immune activation with latent Epstein-Barr virus in active
      MS lesions.
AB  - OBJECTIVE: To determine whether the activation of innate immune responses, which
      can be elicited by pathogenic and endogenous triggers, is associated with the
      presence of Epstein-Barr virus (EBV) infection in the multiple sclerosis (MS)
      brain. METHODS: White matter postmortem MS (n = 10) and control tissue (n = 11)
      was analyzed for the expression of the proinflammatory cytokine interferon alpha
      (IFNalpha) by immunohistochemistry and for EBV by using the highly sensitive
      method of EBV-encoded RNA (EBER) in situ hybridization. RESULTS: We detected
      overexpression of IFNalpha in active areas of white matter MS lesions but not in
      inactive MS lesions, normal-appearing white matter, or normal brains. The
      presence of IFNalpha in macrophages and microglia (expressing human leukocyte
      antigen class II) is suggestive of local production as part of an acute
      inflammatory process. Interestingly, EBERs were also specifically detected in
      areas where IFNalpha was overexpressed in these preselected active MS lesions.
      EBER+ cells were also found in CNS lymphoma and stroke cases, but were absent in
      other control brains. We next addressed a potential mechanism, e.g., the role of
      EBERs in eliciting IFNalpha production, and transfected EBERs into human
      embryonic kidney (HEK) cells. We used HEK cells that stably expressed Toll-like
      receptor-3, which recognizes double-stranded RNAs, associated with many viral
      infections. EBERs elicited IFNalpha production in vitro. CONCLUSION: These
      findings suggest that latent EBV infection may contribute to the inflammatory
      milieu in active MS lesions by activating innate immune responses, e.g., IFNalpha
      production. Unraveling the underlying mechanisms may help in uncovering causal
      pathways and developing better treatment strategies for MS and other
      neuroinflammatory diseases.

PMID- 22156988
TI  - Evidence-based guideline: clinical evaluation and treatment of transverse
      myelitis: report of the Therapeutics and Technology Assessment Subcommittee of
      the American Academy of Neurology.
AB  - OBJECTIVE: To assess the evidence for diagnostic tests and therapies for
      transverse myelitis (TM) and make evidence-based recommendations. METHODS: A
      review of the published literature from 1966 to March 2009 was performed, with
      evidence-based classification of relevant articles. RECOMMENDATIONS: Level B
      recommendations: neuromyelitis optica (NMO)-immunoglobulin G (IgG) antibodies
      should be considered useful to determine TM cause in patients presenting with
      clinical acute complete transverse myelitis (ACTM) features. The presence of NMO
      IgG antibodies (aquaporin-4-specific antibodies) should be considered useful in
      determining increased TM recurrence risk. Level C recommendations: in suspected
      TM, distinction between ACTM or acute partial transverse myelitis may be
      considered useful to determine TM etiology and risk for relapse (more common with
      APTM). Age and gender may be considered useful to determine etiology in patients
      presenting with TM syndrome, with spinal infarcts seen more often in older
      patients and more female than male patients having TM due to multiple sclerosis
      (MS). Brain MRI characteristics consistent with those of MS may be considered
      useful to predict conversion to MS after a first partial TM episode. Longer
      spinal lesions extending over >3 vertebral segments may be considered useful in
      determining NMO vs MS. CSF examination for cells and oligoclonal bands may be
      considered useful to determine the cause of the TM syndrome. Plasma exchange may
      be considered in patients with TM who fail to improve after corticosteroid
      treatment. Rituximab may be considered in patients with TM due to NMO to decrease
      the number of relapses. Level U recommendations: there is insufficient evidence
      to support or refute the efficacy of other TM therapies or the usefulness of
      ethnicity to determine the cause of a subacute myelopathy.

PMID- 22156989
TI  - Adaptive quantization-parameter clip scheme for smooth quality in H.264/AVC.
AB  - In this paper, we investigate the issues over the smooth quality and the smooth
      bit rate during rate control (RC) in H.264/AVC. An adaptive quantization
      parameter  (Q(p))  clip scheme is proposed to optimize the quality smoothness
      while keeping the bit-rate fluctuation at an acceptable level. First, the frame
      complexity variation is studied by defining a complexity ratio between two nearby
      frames. Second, the range of the generated bits is analyzed to prevent the
      encoder buffer from overflow and underflow. Third, based on the safe range of the
      generated bits, an optimal  Q(p)  clip range is developed to reduce the quality
      fluctuation. Experimental results demonstrate that the proposed  Q(p)  clip
      scheme can achieve excellent performance in quality smoothness and buffer
      regulation.

PMID- 22156990
TI  - Is T2* enough to assess oxygenation? Quantitative blood oxygen level-dependent
      analysis in brain tumor.
AB  - PURPOSE: To analyze the contribution of the transverse relaxation parameter (T2),
      macroscopic field inhomogeneities (B0), and blood volume fraction (BVf) to blood
      oxygen level-dependent (BOLD)-based magnetic resonance (MR) measurements of blood
      oxygen saturation (SO2) obtained in a brain tumor model. MATERIALS AND METHODS:
      This study was approved by the local committee for animal care and use.
      Experiments were performed in accordance with permit 380 820 from the French
      Ministry of Agriculture. The 9L gliosarcoma cells were implanted in the brain of
      eight rats. Fifteen days later, 4.7-T MR examinations were performed to estimate
      T2*, T2, BVf, and T2*DeltaB0corrected in the tumor and contralateral regions. MR
      estimates of SO2 were derived by combining T2, BVf, and T2*DeltaB0corrected
      according to a recently described quantitative BOLD approach. Scatterplots and
      linear regression analysis were used to identify correlation between parameters.
      Paired Student t tests were used to compare the tumor region with the
      contralateral region. RESULTS: No significant correlations were found between T2*
      and any parameter in either tumor tissue or healthy tissue. T2* in the tumor and
      T2* in the uninvolved contralateral brain were the same (36 msec+/-4 [standard
      deviation] vs 36 msec+/-5, respectively), which might suggest similar
      oxygenation. Adding T2 information (98 msec+/-7 vs 68 msec+/-2, respectively)
      alone yields results that suggest apparent hypo-oxygenation of the tumor, while
      incorporating BVf (5.3%+/-0.6 vs 2.6%+/-0.3, respectively) alone yields results
      that suggest apparent hyperoxygenation. MR estimates of SO2 obtained with a
      complete quantitative BOLD analysis, although not correlated with T2* values,
      suggest normal oxygenation (68%+/-3 vs 65%+/-4, respectively). MR estimates of
      SO2 obtained in the contralateral tissue agree with previously reported values.
      CONCLUSION: Additional measurements, such as BVf, T2, and B0, are needed to
      obtain reliable information on oxygenation with BOLD MR imaging. The proposed
      quantitative BOLD approach, which includes these measurements, appears to be a
      promising tool with which to map tumor oxygenation.

PMID- 22156991
TI  - Dose-dependent artifact in the far wall of the carotid artery at dynamic contrast
      enhanced US.
AB  - PURPOSE: To quantify a pseudoenhancement phenomenon observed during dynamic
      contrast material-enhanced ultrasonography (US) of the carotid artery, both in
      vitro and in vivo. MATERIALS AND METHODS: Ethical approval was obtained prior to
      commencing this prospective case series, and each patient gave written informed
      consent. Thirty-one patients with 50%-99% internal carotid artery stenosis
      underwent dynamic contrast-enhanced US of the carotid bifurcation with use of 2
      mL of microbubbles. In the final 10 patients, an additional 1 mL bolus was
      administered after 15 minutes. Raw linear digital imaging and communications in
      medicine data were analyzed offline. Regions of interest were drawn within the
      common carotid artery lumen and immediately adjacent to the lumen in the near and
      far wall adventitia. Peak intensity was measured. An in vitro experiment with a
      single-channel flow phantom was also performed. This apparatus consisted of an 8
      mm-diameter latex tube placed in a tissue-mimicking fluid. Microbubble
      concentrations of 0.02%, 0.1%, 0.5%, 1%, and 2% were pumped into the tube.
      Regions of interest were drawn in a similar fashion to the in vivo experiments,
      and peak intensity was measured. The Wilcoxon signed rank and paired t tests were
      used to compare the difference between the near and far wall signal intensities
      at each dose; a multiplication factor comparing near and far wall signal
      intensity was derived. RESULTS: The far wall of the common carotid artery was
      significantly more echogenic than the near wall at 2 mL contrast agent doses
      (P<.0001, n=31), and the far wall signal intensity increased synchronously with
      that of the lumen. The difference in signal intensity between near and far wall
      regions was significantly greater at 2 mL than at 1 mL (P=.012, n=10). In vitro,
      the phantom tubing demonstrated a similar pattern and magnitude of enhancement to
      that seen in vivo. CONCLUSION: A dose-dependent, nonlinear propagation artifact
      known as pseudoenhancement occurs in the far wall adventitia of the carotid
      artery and should not be mistaken as a marker of plaque vulnerability.

PMID- 22156992
TI  - Role of radiologic imaging in irritable bowel syndrome: evidence-based review.
AB  - PURPOSE: To critically evaluate the current literature in an effort to establish
      the current role of radiologic imaging (computed tomography, magnetic resonance
      imaging, ultrasonography [US], fluoroscopy, conventional film radiography) in
      irritable bowel syndrome (IBS). MATERIALS AND METHODS: The term "irritable bowel
      syndrome" was used to search Clinical Evidence, UpToDate, Cochrane Library, TRIP,
      and National Institute for Health and Clinical Excellence databases and the
      American College of Physicians Journal Club and Evidence-Based Medicine online.
      PubMed was searched by using medical subject headings ("irritable bowel
      syndrome;" "colonic diseases, functional;" "diagnosis;" "colonography;" "computed
      tomographic (CT)") and the dates January 1, 1985 to July 1, 2010. Appraisal was
      independently performed by two reviewers who followed the Oxford Centre for
      Evidence Based Medicine practice criteria. RESULTS: No systematic review (SR)
      specifically examined radiologic imaging in IBS; however, in the secondary
      literature, five relevant SRs or guidelines partially addressed this topic. A
      PubMed search identified 1451 articles, 111 of which at least partially addressed
      radiologic imaging. Of these, seven valid articles (two SRs and five primary
      research articles) were identified. The five primary research articles examined
      either colonic investigations (colonoscopy and barium enema examination) (n=5) or
      US (n=2) or both (n=2). Structural disease found infrequently in patients with
      IBS-type symptoms included diverticulosis, colorectal cancer, celiac disease,
      inflammatory bowel disease, and ovarian cancer. The incidence of structural
      disease in patients with concerning symptoms was low. CONCLUSION: Although widely
      used, there is a surprising paucity of evidence guiding radiologic imaging in
      IBS. Radiologic imaging may not be required in patients with IBS without
      potentially concerning symptoms but should be considered where such symptoms
      exist, and choice of imaging study should be influenced by predominant symptoms.
      Definitive recommendations must await further research.

PMID- 22156993
TI  - Pulmonary Nodules: growth rate assessment in patients by using serial CT and
      three-dimensional volumetry.
AB  - PURPOSE: To determine the precision of a three-dimensional (3D) method for
      measuring the growth rate of solid and subsolid nodules and its ability to detect
      abnormal growth rates. MATERIALS AND METHODS: This study was approved by the
      Institutional Research Board and was HIPAA compliant. Informed consent was
      waived. The growth rates of 123 lung nodules in 59 patients who had undergone
      lung cancer screening computed tomography (CT) were measured by using a 3D
      semiautomated computer-assisted volume method. Clinical stability was established
      with long-term CT follow-up (mean, 6.4 years+/-1.9 [standard deviation]; range,
      2.0-8.5 years). A mean of 4.1 CT examinations per patient+/-1.2 (range, two to
      seven CT examinations per patient) was analyzed during 2.4 years+/-0.5 after
      baseline CT. Nodule morphology, attenuation, and location were characterized. The
      analysis of standard deviation of growth rate in relation to time between scans
      yielded a normative model for detecting abnormal growth. RESULTS: Growth rate
      precision increased with greater time between scans. Overall estimate for
      standard deviation of growth rate, on the basis of 939 growth rate determinations
      in clinically stable nodules, was 36.5% per year. Peripheral location (P=.01;
      37.1% per year vs 25.6% per year) and adjacency to pleural surface (P=.05; 38.9%
      per year vs 34.0% per year) significantly increased standard deviation of growth
      rate. All eight malignant nodules had an abnormally high growth rate detected. By
      using 3D volumetry, growth rate-based diagnosis of malignancy was made at a mean
      of 183 days+/-158, compared with radiologic or clinical diagnosis at 344 days+/
      284. CONCLUSION: A normative model derived from the variability of growth rates
      of nodules that were stable for an average of 6.4 years may enable identification
      of lung cancer.

PMID- 22156994
TI  - Curcumin:  a novel Stat3 pathway inhibitor for chemoprevention of lung cancer.
AB  - Multiple studies from independent groups find evidence for signal transducer and
      activator of transcription 3 (Stat3) activation in nearly 50% of lung cancers,
      suggesting a functional role for this target in subsets of lung cancer. On the
      basis of the existing evidence, we hypothesized that bioavailable curcuminoid
      complex may modulate lung carcinogenesis, primarily by inhibiting Stat3
      activation. With the safety of this being botanically well established, the
      objective of these studies was to test our hypothesis in vitro and in vivo in an
      effort to inform the design of a phase II chemoprevention trial in former
      smokers. We treated non-tumor-derived, normal (but immortalized) human bronchial
      epithelial cells (AALE) (Lundberg et al., 2002; Pillai et al., 2011) and lung
      adenocarcinoma-derived cells (H441) with bioactive curcumin C3 complex.
      Asynchronous cells in each case were treated with curcumin for 24 h, followed by
      immunoblotting for Stat3 and activated Stat3-P, prior signal of which was used
      for normalization. We also completed a preclinical trial in which 12 mice were
      randomly divided into three groups and subjected to 3 days or 9 days of curcumin
      intraperitoneal injections, followed by analysis of lung tissues for Stat3-P
      changes and growth suppressive effects of the curcumin. The growth suppressive
      effects were measured using Cyclin D1 and the replicative helicase subunit, Mcm2,
      as surrogates for the proliferative capacity of the tissues. In-vitro studies
      with curcuminoid complex demonstrated that the activity of Stat3 in both normal
      bronchoepithelial cells and lung cancer-derived cells is sensitive to curcumin
      exposure. In a dose-dependent manner, curcumin treatment resulted in significant
      suppression of Stat3 phosphorylation and reduction in the proliferative capacity
      of both cell types. In the preclinical trial with rodent models, curcumin reduced
      Stat3-P and the proliferative markers CycD1 and Mcm2 in mice lung tissues in
      vivo. These culture and preclinical studies indicate that the activity of the
      Stat3 pathway can be suppressed by curcumin treatment, concomitant with a
      reduction in cell proliferation, supporting our hypothesis that inhibition of the
      Stat3 pathway represents at least one important mechanism by which curcumin
      elicits its effects on the bronchoepithelium. These data provide a rationale for
      the use of curcumin as a promising chemopreventive agent in high-risk populations
      such as former smokers.

PMID- 22156995
TI  - Cancer control and prevention in Europe:  the contribution of the European
      Journal of Cancer Prevention.

PMID- 22156996
TI  - The root causes of socioeconomic differentials in cancer and cardiovascular
      mortality in Greece.
AB  - Lower socioeconomic groups experience higher rates of premature mortality in
      comparison with the upper socioeconomic groups. We have undertaken a study in
      Greece to assess socioeconomic differentials in overall, cancer, and
      cardiovascular (CVD) mortality and to identify their possible roots, using
      educational attainment to indicate socioeconomic status. Among participants in
      the general population, the Greek European Prospective Investigation into Cancer
      and Nutrition cohort, 23 697 individuals with no prevalent cancer or CVD disease
      at enrollment and with complete information on education and established or
      likely mortality risk factors, were followed up for an average of 9.6 years. Age
      adjusted odds ratios of the prevalence of risk factors by education and sex were
      calculated through logistic regression and mortality ratios were estimated
      through Cox regression. With respect to overall and CVD mortality, the results
      indicated a 50% to more than 100% difference between the extreme categories of
      educational attainment. No gradient was, however, observed in cancer mortality.
      Obesity, poor diet, hypertension, and low physical activity were more prevalent
      among the least educated participants, but smoking was almost as common among the
      more and the less educated men and strikingly more common among the higher
      educated women. Likely intermediates did not explain more than one-third of the
      excess mortality among the less educated persons. In the Greek population, strong
      socioeconomic gradients were observed in the overall and CVD mortality, but not
      in cancer mortality. Established risk factors for premature mortality explained
      only a fraction of the observed gradients.

PMID- 22156997
TI  - Cadmium from zinc smelter emission and variation in cancer incidence:  the
      hierarchy of evidence.

PMID- 22156998
TI  - Efficient model learning methods for actor-critic control.
AB  - We propose two new actor-critic algorithms for reinforcement learning. Both
      algorithms use local linear regression (LLR) to learn approximations of the
      functions involved. A crucial feature of the algorithms is that they also learn a
      process model, and this, in combination with LLR, provides an efficient policy
      update for faster learning. The first algorithm uses a novel model-based update
      rule for the actor parameters. The second algorithm does not use an explicit
      actor but learns a reference model which represents a desired behavior, from
      which desired control actions can be calculated using the inverse of the learned
      process model. The two novel methods and a standard actor-critic algorithm are
      applied to the pendulum swing-up problem, in which the novel methods achieve
      faster learning than the standard algorithm.

PMID- 22156999
TI  - Mining visual collocation patterns via self-supervised subspace learning.
AB  - Traditional text data mining techniques are not directly applicable to image data
      which contain spatial information and are characterized by high-dimensional
      visual features. It is not a trivial task to discover meaningful visual patterns
      from images because the content variations and spatial dependence in visual data
      greatly challenge most existing data mining methods. This paper presents a novel
      approach to coping with these difficulties for mining visual collocation
      patterns. Specifically, the novelty of this work lies in the following new
      contributions: 1) a principled solution to the discovery of visual collocation
      patterns based on frequent itemset mining and 2) a self-supervised subspace
      learning method to refine the visual codebook by feeding back discovered patterns
      via subspace learning. The experimental results show that our method can discover
      semantically meaningful patterns efficiently and effectively.

PMID- 22157000
TI  - YajL, prokaryotic homolog of parkinsonism-associated protein DJ-1, functions as a
      covalent chaperone for thiol proteome.
AB  - YajL is the closest Escherichia coli homolog of the Parkinsonism-associated
      protein DJ-1, a multifunctional oxidative stress response protein whose
      biochemical function remains unclear. We recently reported the aggregation of
      proteins in a yajL mutant in an oxidative stress-dependent manner and that YajL
      exhibits chaperone activity. Here, we show that YajL displays covalent chaperone
      and weak protein oxidoreductase activities that are dependent on its exposed
      cysteine 106. It catalyzes reduced RNase oxidation and scrambled RNase
      isomerization and insulin reduction and forms mixed disulfides with many cellular
      proteins upon oxidative stress. The formation of mixed disulfides was detected by
      immunoblotting bacterial extracts with anti-YajL antibodies under nonreducing
      conditions. Disulfides were purified from bacterial extracts on a YajL affinity
      column, separated by nonreducing-reducing SDS-PAGE, and identified by mass
      spectrometry. Covalent YajL substrates included ribosomal proteins, aminoacyl
      tRNA synthetases, chaperones, catalases, peroxidases, and other proteins
      containing cysteines essential for catalysis or FeS cluster binding, such as
      glyceraldehyde-3-phosphate dehydrogenase, aldehyde dehydrogenase, aconitase, and
      FeS cluster-containing subunits of respiratory chains. In addition, we show that
      DJ-1 also forms mixed disulfides with cytoplasmic proteins upon oxidative stress.
      These results shed light on the oxidative stress-dependent chaperone function of
      YajL and identify YajL substrates involved in translation, stress protection,
      protein solubilization, and metabolism. They reveal a crucial role for cysteine
      106 and suggest that DJ-1 also functions as a covalent chaperone. These findings
      are consistent with several defects observed in yajL or DJ-1 mutants, including
      translational defects, protein aggregation, oxidative stress sensitivity, and
      metabolic deficiencies.

PMID- 22157001
TI  - Genotype-phenotype correlations in Lesch-Nyhan disease: moving beyond the gene.
AB  - Lesch-Nyhan disease and its attenuated variants are caused by mutations in the
      HPRT1 gene, which encodes the purine recycling enzyme hypoxanthine-guanine
      phosphoribosyltransferase. The mutations are heterogeneous, with more than 400
      different mutations already documented. Prior efforts to correlate variations in
      the clinical phenotype with different mutations have suggested that milder
      phenotypes typically are associated with mutants that permit some residual enzyme
      function, whereas the most severe phenotype is associated with null mutants.
      However, multiple exceptions to this concept have been reported. In the current
      studies 44 HPRT1 mutations associated with a wide spectrum of clinical phenotypes
      were reconstructed by site-directed mutagenesis, the mutant enzymes were
      expressed in vitro and purified, and their kinetic properties were examined
      toward their substrates hypoxanthine, guanine, and phosphoribosylpyrophosphate.
      The results provide strong evidence for a correlation between disease severity
      and residual catalytic activity of the enzyme (k(cat)) toward each of its
      substrates as well as several mechanisms that result in exceptions to this
      correlation. There was no correlation between disease severity and the affinity
      of the enzyme for its substrates (K(m)). These studies provide a valuable model
      for understanding general principles of genotype-phenotype correlations in human
      disease, as the mechanisms involved are applicable to many other disorders.

PMID- 22157002
TI  - Toward convergence of experimental studies and theoretical modeling of the
      chromatin fiber.
AB  - Understanding the structural organization of eukaryotic chromatin and its control
      of gene expression represents one of the most fundamental and open challenges in
      modern biology. Recent experimental advances have revealed important
      characteristics of chromatin in response to changes in external conditions and
      histone composition, such as the conformational complexity of linker DNA and
      histone tail domains upon compact folding of the fiber. In addition, modeling
      studies based on high-resolution nucleosome models have helped explain the
      conformational features of chromatin structural elements and their interactions
      in terms of chromatin fiber models. This minireview discusses recent progress and
      evidence supporting structural heterogeneity in chromatin fibers, reconciling
      apparently contradictory fiber models.

PMID- 22157003
TI  - Nuclear import of the yeast hexokinase 2 protein requires alpha/beta-importin
      dependent pathway.
AB  - Hexokinase 2 (Hxk2) from Saccharomyces cerevisiae was one of the first metabolic
      enzymes described as a multifunctional protein. Hxk2 has a double subcellular
      localization and role, it functions as a glycolytic enzyme in the cytoplasm and
      as a regulator of gene transcription of several Mig1-regulated genes in the
      nucleus. However, the mechanism by which Hxk2 enters in the nucleus was unknown
      until now. Here, we report that the Hxk2 protein is an import substrate of the
      carriers alpha-importin (Kap60 in yeast) and beta-importin (Kap95 in yeast). We
      also show that the Hxk2 nuclear import and the binding of Hxk2 with Kap60 are
      glucose-dependent and involve one lysine-rich nuclear localization sequence
      (NLS), located between lysine 6 and lysine 12. Moreover, Kap95 facilitates the
      recognition of the Hxk2 NLS1 motif by Kap60 and both importins are essential for
      Hxk2 nuclear import. It is also demonstrated that Hxk2 nuclear import and its
      binding to Kap95 and Kap60 depend on the Gsp1-GTP/GDP protein levels. Thus, our
      study uncovers Hxk2 as a new cargo for the alpha/beta-importin pathway of S.
      cerevisiae.

PMID- 22157004
TI  - RNA polymerase II carboxyl-terminal domain phosphorylation regulates protein
      stability of the Set2 methyltransferase and histone H3 di- and trimethylation at
      lysine 36.
AB  - Methylation of lysine 36 on histone H3 (H3K36) is catalyzed by the Set2
      methyltransferase and is linked to transcriptional regulation. Previous studies
      have shown that trimethylation of H3K36 by Set2 is directed through its
      association with the phosphorylated repeats of the RNA polymerase C-terminal
      domain (RNAPII CTD). Here, we show that disruption of this interaction through
      the use of yeast mutants defective in CTD phosphorylation at serine 2 results in
      a destabilization of Set2 protein levels and H3K36 methylation. Consistent with
      this, we find that Set2 has a short half-life and is co-regulated, with RNAPII
      CTD phosphorylation levels, during logarithmic growth in yeast. To probe the
      functional consequence of uncoupling Set2-RNAPII regulation, we expressed a
      truncated and more stable form of Set2 that is capable of dimethylation but not
      trimethylation in vivo. Results of high throughput synthetic genetic analyses
      show that this Set2 variant has distinct genetics from either SET2 or set2Delta
      and is synthetically sick or lethal with a number of transcription elongation
      mutants. Collectively, these results provide molecular insight into the
      regulation of Set2 protein levels that influence H3K36 methylation states.

PMID- 22157005
TI  - Engineering hyperthermophilic archaeon Pyrococcus furiosus to overproduce its
      cytoplasmic [NiFe]-hydrogenase.
AB  - The cytoplasmic hydrogenase (SHI) of the hyperthermophilic archaeon Pyrococcus
      furiosus is an NADP(H)-dependent heterotetrameric enzyme that contains a nickel
      iron catalytic site, flavin, and six iron-sulfur clusters. It has potential
      utility in a range of bioenergy systems in vitro, but a major obstacle in its use
      is generating sufficient amounts. We have engineered P. furiosus to overproduce
      SHI utilizing a recently developed genetic system. In the overexpression (OE-SHI)
      strain, transcription of the four-gene SHI operon was under the control of a
      strong constitutive promoter, and a Strep-tag II was added to the N terminus of
      one subunit. OE-SHI and wild-type P. furiosus strains had similar rates of growth
      and H(2) production on maltose. Strain OE-SHI had a 20-fold higher transcription
      of the polycistronic hydrogenase mRNA encoding SHI, and the specific activity of
      the cytoplasmic hydrogenase was ~10-fold higher when compared with the wild-type
      strain, although the expression levels of genes encoding processing and
      maturation of SHI were the same in both strains. Overexpressed SHI was purified
      by a single affinity chromatography step using the Strep-tag II, and it and the
      native form had comparable activities and physical properties. Based on protein
      yield per gram of cells (wet weight), the OE-SHI strain yields a 100-fold higher
      amount of hydrogenase when compared with the highest homologous [NiFe]
      hydrogenase system previously reported (from Synechocystis). This new P. furiosus
      system will allow further engineering of SHI and provide hydrogenase for
      efficient in vitro biohydrogen production.

PMID- 22157006
TI  - Structural and mechanistic insights into the interaction of cytochrome P4503A4
      with bromoergocryptine, a type I ligand.
AB  - Cytochrome P4503A4 (CYP3A4), a major human drug-metabolizing enzyme, is
      responsible for the oxidation and clearance of the majority of administered
      drugs. One of the CYP3A4 substrates is bromoergocryptine (BEC), a dopamine
      receptor agonist prescribed for the inhibition of prolactin secretion and
      treatment of Parkinson disease, type 2 diabetes, and several other pathological
      conditions. Here we present a 2.15 A crystal structure of the CYP3A4-BEC complex
      in which the drug, a type I heme ligand, is bound in a productive mode. The
      manner of BEC binding is consistent with the in vivo metabolite analysis and
      identifies the 8' and 9' carbons of the proline ring as the primary sites of
      oxidation. The crystal structure predicts the importance of Arg(212) and Thr(224)
      for binding of the tripeptide and lysergic moieties of BEC, respectively, which
      we confirmed experimentally. Our data support a three-step BEC binding model
      according to which the drug binds first at a peripheral site without perturbing
      the heme spectrum and then translocates into the active site cavity, where
      formation of a hydrogen bond between Thr(224) and the N1 atom of the lysergic
      moiety is followed by a slower conformational readjustment of the tripeptide
      group modulated by Arg(212).

PMID- 22157007
TI  - Regulation of glycolytic enzyme phosphoglycerate mutase-1 by Sirt1 protein
      mediated deacetylation.
AB  - Emerging proteomic evidence suggests that acetylation of metabolic enzymes is a
      prevalent post-translational modification. In a few recent reports, acetylation
      down-regulated activity of specific enzymes in fatty acid oxidation, urea cycle,
      electron transport, and anti-oxidant pathways. Here, we reveal that the
      glycolytic enzyme phosphoglycerate mutase-1 (PGAM1) is negatively regulated by
      Sirt1, a member of the NAD(+)-dependent protein deacetylases. Acetylated PGAM1
      displays enhanced activity, although Sirt1-mediated deacetylation reduces
      activity. Acetylation sites mapped to the C-terminal "cap," a region previously
      known to affect catalytic efficiency. Overexpression of a constitutively active
      variant (acetylated mimic) of PGAM1 stimulated flux through glycolysis. Under
      glucose restriction, Sirt1 levels dramatically increased, leading to PGAM1
      deacetylation and attenuated activity. Previously, Sirt1 has been implicated in
      the adaptation from glucose to fat burning. This study (i) demonstrates that
      protein acetylation can stimulate metabolic enzymes, (ii) provides biochemical
      evidence that glycolysis is modulated by reversible acetylation, and (iii)
      demonstrates that PGAM1 deacetylation and activity are directly controlled by
      Sirt1.

PMID- 22157008
TI  - Multiple members of the UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase
      family are essential for viability in Drosophila.
AB  - Mucin-type O-glycosylation represents a major form of post-translational
      modification that is conserved across most eukaryotic species. This type of
      glycosylation is initiated by a family of enzymes (GalNAc-Ts in mammals and
      PGANTs in Drosophila) whose members are expressed in distinct spatial and
      temporal patterns during development. Previous work from our group demonstrated
      that one member of this family is essential for viability and another member
      modulates extracellular matrix composition and integrin-mediated cell adhesion
      during development. To investigate whether other members of this family are
      essential, we employed RNA interference (RNAi) to each gene in vivo. Using this
      approach, we identified 4 additional pgant genes that are required for viability.
      Ubiquitous RNAi to pgant4, pgant5, pgant7, or the putative glycosyltransferase
      CG30463 resulted in lethality. Tissue-specific RNAi was also used to define the
      specific organ systems and tissues in which each essential family member is
      required. Interestingly, each essential pgant had a unique complement of tissues
      in which it was required. Additionally, certain tissues (mesoderm, digestive
      system, and tracheal system) required more than one pgant, suggesting unique
      functions for specific enzymes in these tissues. Expanding upon our RNAi results,
      we found that conventional mutations in pgant5 resulted in lethality and specific
      defects in specialized cells of the digestive tract, resulting in loss of proper
      digestive system acidification. In summary, our results highlight essential roles
      for O-glycosylation and specific members of the pgant family in many aspects of
      development and organogenesis.

PMID- 22157009
TI  - Leiomodin 1, a new serum response factor-dependent target gene expressed
      preferentially in differentiated smooth muscle cells.
AB  - Smooth muscle cell (SMC) differentiation is defined largely by a number of cell
      restricted genes governed directly by the serum response factor (SRF)/myocardin
      (MYOCD) transcriptional switch. Here, we describe a new SRF/MYOCD-dependent, SMC
      restricted gene known as Leiomodin 1 (Lmod1). Conventional and quantitative RT
      PCRs indicate that Lmod1 mRNA expression is enriched in SMC-containing tissues of
      the mouse, whereas its two paralogs, Lmod2 and Lmod3, exhibit abundant expression
      in skeletal and cardiac muscle with very low levels in SMC-containing tissues.
      Western blotting and immunostaining of various adult and embryonic mouse tissues
      further confirm SMC-specific expression of the LMOD1 protein. Comparative genomic
      analysis of the human LMOD1 and LMOD2 genes with their respective mouse and rat
      orthologs shows high conservation between the three exons and several noncoding
      sequences, including the immediate 5' promoter region. Two conserved CArG boxes
      are present in both the LMOD1 and LMOD2 promoter regions, although LMOD1 displays
      much higher promoter activity and is more responsive to SRF/MYOCD stimulation.
      Gel shift assays demonstrate clear binding between SRF and the two CArG boxes in
      human LMOD1. Although the CArG boxes in LMOD1 and LMOD2 are similar, only LMOD1
      displays SRF or MYOCD-dependent activation. Transgenic mouse studies reveal wild
      type LMOD1 promoter activity in cardiac and vascular SMC. Such activity is
      abolished upon mutation of both CArG boxes. Collectively, these data demonstrate
      that Lmod1 is a new SMC-restricted SRF/MYOCD target gene.

PMID- 22157010
TI  - Functional architecture of the outer arm dynein conformational switch.
AB  - Dynein light chain 1 (LC1/DNAL1) is one of the most highly conserved components
      of ciliary axonemal outer arm dyneins, and it associates with both a heavy chain
      motor unit and tubulin located within the A-tubule of the axonemal outer doublet
      microtubules. In a variety of model systems, lack of LC1 or expression of mutant
      forms leads to profound defects in ciliary motility, including the failure of the
      hydrodynamic coupling needed for ciliary metachronal synchrony, random stalling
      during the power/recovery stroke transition, an aberrant response to imposed
      viscous load, and in some cases partial failure of motor assembly. These
      phenotypes have led to the proposal that LC1 acts as part of a mechanical switch
      to control motor function in response to alterations in axonemal curvature. Here
      we have used NMR chemical shift mapping to define the regions perturbed by a
      series of mutations in the C-terminal domain that yield a range of phenotypic
      effects on motility. In addition, we have identified the subdomain of LC1
      involved in binding microtubules and characterized the consequences of an Asn ->
      Ser alteration within the terminal leucine-rich repeat that in humans causes
      primary ciliary dyskinesia. Together, these data define a series of functional
      subdomains within LC1 and allow us to propose a structural model for the
      organization of the dynein heavy chain-LC1-microtubule ternary complex that is
      required for the coordinated activity of dynein motors in cilia.

PMID- 22157011
TI  - Tryptamine-gallic acid hybrid prevents non-steroidal anti-inflammatory drug
      induced gastropathy: correction of mitochondrial dysfunction and inhibition of
      apoptosis in gastric mucosal cells.
AB  - We have investigated the gastroprotective effect of SEGA (3a), a newly
      synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti
      inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a)
      prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and
      dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing
      gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of
      mitochondrial superoxide anion (O(2)(.-)) and intramitochondrial free iron
      released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS,
      as is evident from the inhibition of indomethacin-induced mitochondrial protein
      carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects
      indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective
      electron transport chain function, collapse of transmembrane potential, and loss
      of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction
      but also inhibits the activation of the mitochondrial pathway of apoptosis by
      indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2
      and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits
      indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa.
      Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the
      healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA
      (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric
      mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an
      immense potential to be a novel gastroprotective agent against NSAID-induced
      gastropathy.

PMID- 22157012
TI  - Fluorescence correlation spectroscopy to monitor Kai protein-based circadian
      oscillations in real time.
AB  - Dynamic protein-protein interactions play an essential role in cellular
      regulatory systems. The cyanobacterial circadian clock is an oscillatory system
      that can be reconstituted in vitro by mixing ATP and three clock proteins: KaiA,
      KaiB, and KaiC. Association and dissociation of KaiB from KaiC-containing
      complexes are critical to circadian phosphorylation and dephosphorylation of
      KaiC. We developed an automated and noninvasive method to monitor dynamic complex
      formation in real time using confocal fluorescence correlation spectroscopy (FCS)
      and uniformly labeled KaiB as a probe. A nanomolar concentration of the labeled
      KaiB for FCS measurement did not interfere with the oscillatory system but
      behaved similarly to the wild-type one during the measurement period (>5 days).
      The fluorescent probe was stable against repeated laser exposure. As an
      application, we show that this detection system allowed analysis of the dynamics
      of both long term circadian oscillations and short term responses to temperature
      changes (~10 min) in the same sample. This suggested that a phase shift of the
      clock with a high temperature pulse occurred just after the stimulus through
      dissociation of KaiB from the KaiC complex. This monitoring method should improve
      our understanding of the mechanisms underlying this cellular circadian oscillator
      and provide a means to assess dynamic protein interactions in biological systems
      characterized by rates similar to those observed with the Kai proteins.

PMID- 22157013
TI  - Analysis and functional prediction of reactive cysteine residues.
AB  - Cys is much different from other common amino acids in proteins. Being one of the
      least abundant residues, Cys is often observed in functional sites in proteins.
      This residue is reactive, polarizable, and redox-active; has high affinity for
      metals; and is particularly responsive to the local environment. A better
      understanding of the basic properties of Cys is essential for interpretation of
      high-throughput data sets and for prediction and classification of functional Cys
      residues. We provide an overview of approaches used to study Cys residues, from
      methods for investigation of their basic properties, such as exposure and pK(a),
      to algorithms for functional prediction of different types of Cys in proteins.

PMID- 22157014
TI  - Lipin-1 phosphatidic phosphatase activity modulates phosphatidate levels to
      promote peroxisome proliferator-activated receptor gamma (PPARgamma) gene
      expression during adipogenesis.
AB  - Adipose tissue plays a key role in metabolic homeostasis. Disruption of the Lpin1
      gene encoding lipin-1 causes impaired adipose tissue development and function in
      rodents. Lipin-1 functions as a phosphatidate phosphatase (PAP) enzyme in the
      glycerol 3-phosphate pathway for triglyceride storage and as a transcriptional
      coactivator/corepressor for metabolic nuclear receptors. Previous studies
      established that lipin-1 is required at an early step in adipocyte
      differentiation for induction of the adipogenic gene transcription program,
      including the key regulator peroxisome proliferator-activated receptor gamma
      (PPARgamma). Here, we investigate the requirement of lipin-1 PAP versus
      coactivator function in the establishment of Pparg expression during adipocyte
      differentiation. We demonstrate that PAP activity supplied by lipin-1, lipin-2,
      or lipin-3, but not lipin-1 coactivator activity, can rescue Pparg gene
      expression and lipogenesis during adipogenesis in lipin-1-deficient
      preadipocytes. In adipose tissue from lipin-1-deficient mice, there is an
      accumulation of phosphatidate species containing a range of medium chain fatty
      acids and an activation of the MAPK/extracellular signal-related kinase (ERK)
      signaling pathway. Phosphatidate inhibits differentiation of cultured adipocytes,
      and this can be rescued by the expression of lipin-1 PAP activity or by
      inhibition of ERK signaling. These results emphasize the importance of lipid
      intermediates as choreographers of gene regulation during adipogenesis, and the
      results highlight a specific role for lipins as determinants of levels of a
      phosphatidic acid pool that influences Pparg expression.

PMID- 22157015
TI  - Mitochondrial disulfide relay: redox-regulated protein import into the
      intermembrane space.
AB  - 99% of all mitochondrial proteins are synthesized in the cytosol, from where they
      are imported into mitochondria. In contrast to matrix proteins, many proteins of
      the intermembrane space (IMS) lack presequences and are imported in an oxidation
      driven reaction by the mitochondrial disulfide relay. Incoming polypeptides are
      recognized and oxidized by the IMS-located receptor Mia40. Reoxidation of Mia40
      is facilitated by the sulfhydryl oxidase Erv1 and the respiratory chain. Although
      structurally unrelated, the mitochondrial disulfide relay functionally resembles
      the Dsb (disufide bond) system of the bacterial periplasm, the compartment from
      which the IMS was derived 2 billion years ago.

PMID- 22157016
TI  - SIRT1 contains N- and C-terminal regions that potentiate deacetylase activity.
AB  - SIRT1 is one of seven mammalian sirtuin (silent information regulator 2-related)
      proteins that harbor NAD(+)-dependent protein deacetylase activity and is
      implicated in multiple metabolic and age-associated pathways and disorders. The
      sirtuin proteins contain a central region of high sequence conservation that is
      required for catalytic activity, but more variable N- and C-terminal regions have
      been proposed to mediate protein specific activities. Here we show that the
      conserved catalytic core domain of SIRT1 has very low catalytic activity toward
      several known protein substrates, but that regions N- and C-terminal to the
      catalytic core potentiate catalytic efficiency by between 12- and 45-fold, with
      the N-terminal domain contributing predominantly to catalytic rate, relatively
      independent of the nature of the acetyl-lysine protein substrate, and the C
      terminal domain contributing significantly to the K(m) for NAD(+). We show that
      the N- and C-terminal regions stimulate SIRT1 deacetylase activity
      intramolecularly and that the C-terminal region stably associates with the
      catalytic core domain to form a SIRT1 holoenzyme. We also demonstrate that the C
      terminal region of SIRT1 can influence the inhibitory activity of some sirtuin
      inhibitors that are known to function through the catalytic core domain.
      Together, these studies highlight the unique properties of the SIRT1 member of
      the sirtuin proteins and have implications for the development of SIRT1-specific
      regulatory molecules.

PMID- 22157017
TI  - Mitophagy plays an essential role in reducing mitochondrial production of
      reactive oxygen species and mutation of mitochondrial DNA by maintaining
      mitochondrial quantity and quality in yeast.
AB  - In mammalian cells, the autophagy-dependent degradation of mitochondria
      (mitophagy) is thought to maintain mitochondrial quality by eliminating damaged
      mitochondria. However, the physiological importance of mitophagy has not been
      clarified in yeast. Here, we investigated the physiological role of mitophagy in
      yeast using mitophagy-deficient atg32- or atg11-knock-out cells. When wild-type
      yeast cells in respiratory growth encounter nitrogen starvation, mitophagy is
      initiated, excess mitochondria are degraded, and reactive oxygen species (ROS)
      production from mitochondria is suppressed; as a result, the mitochondria escape
      oxidative damage. On the other hand, in nitrogen-starved mitophagy-deficient
      yeast, excess mitochondria are not degraded and the undegraded mitochondria
      spontaneously age and produce surplus ROS. The surplus ROS damage the
      mitochondria themselves and the damaged mitochondria produce more ROS in a
      vicious circle, ultimately leading to mitochondrial DNA deletion and the so
      called "petite-mutant" phenotype. Cells strictly regulate mitochondrial quantity
      and quality because mitochondria produce both necessary energy and harmful ROS.
      Mitophagy contributes to this process by eliminating the mitochondria to a basal
      level to fulfill cellular energy requirements and preventing excess ROS
      production.

PMID- 22157019
TI  - Durability of amide N-chloramine biocides to ethylene oxide sterilization.
AB  - The objective of this work is to study the stability of three novel topical
      antimicrobial dressings consisting of amide N-chloramine structures against
      ethylene oxide sterilization. Cotton gauze samples bonded with one of three amide
      N-chloramine structures were subjected to standard ethylene oxide (EtO)
      sterilization. The amounts of amide N-chloramine structures before and after the
      sterilization were quantified to indicate the stabilities of these amide N
      chloramine structures to the sterilization. The samples after sterilization were
      challenged with a clinical isolate of healthcare-associated multidrug-resistant
      Escherichia coli. N-Chloramine structure converted from polymethacrylamide
      (dressing 2) had the highest durability (89.7% retained active chlorine) toward
      EtO sterilization; that from hydantoin (dressing 3; 86.3% retained active
      chlorine) followed; and poly(N-chloroacrylamide) (dressing 1) had the lowest
      (64.0% retained active chlorine). After EtO sterilization, all the samples still
      reduced E. coli presence at 5 minutes of contact, with dressing 2 retaining a log
      6 reduction. The three tested amide N-chloramine structures could all survive EtO
      sterilization while retaining percentages of active chlorine ranging from 64.0 to
      89.7%. Dressing 2 showed the best durability, whereas dressing 1 had the poorest
      durability. With the remaining amounts of amide N-chloramine structures after EtO
      sterilization, all the dressings could still reduce E. coli numbers within 5
      minutes of contact, and dressing 2 resulted in a log 6 reduction in colony count.

PMID- 22157018
TI  - Amino acids regulate expression of antizyme-1 to modulate ornithine decarboxylase
      activity.
AB  - In a glucose-salt solution (Earle's balanced salt solution), asparagine (Asn)
      stimulates ornithine decarboxylase (ODC) activity in a dose-dependent manner, and
      the addition of epidermal growth factor (EGF) potentiates the effect of Asn.
      However, EGF alone fails to activate ODC. Thus, the mechanism by which Asn
      activates ODC is important for understanding the regulation of ODC activity. Asn
      reduced antizyme-1 (AZ1) mRNA and protein. Among the amino acids tested, Asn and
      glutamine (Gln) effectively inhibited AZ1 expression, suggesting a differential
      role for amino acids in the regulation of ODC activity. Asn decreased the
      putrescine-induced AZ1 translation. The absence of amino acids increased the
      binding of eukaryotic initiation factor 4E-binding protein (4EBP1) to 5'-mRNA cap
      and thereby inhibited global protein synthesis. Asn failed to prevent the binding
      of 4EBP1 to mRNA, and the bound 4EBP1 was unphosphorylated, suggesting the
      involvement of the mammalian target of rapamycin (mTOR) in the regulation of AZ1
      synthesis. Rapamycin treatment (4 h) failed to alter the expression of AZ1.
      However, extending the treatment (24 h) allowed expression in the presence of
      amino acids, indicating that AZ1 is expressed when TORC1 signaling is decreased.
      This suggests the involvement of cap-independent translation. However, transient
      inhibition of mTORC2 by PP242 completely abolished the phosphorylation of 4EBP1
      and decreased basal as well as putrescine-induced AZ1 expression. Asn decreased
      the phosphorylation of mTOR-Ser(2448) and AKT-Ser(473), suggesting the inhibition
      of mTORC2. In the absence of amino acids, mTORC1 is inhibited, whereas mTORC2 is
      activated, leading to the inhibition of global protein synthesis and increased
      AZ1 synthesis via a cap-independent mechanism.

PMID- 22157020
TI  - Prognostic value of Tc-99m-MIBI performed during middle course of preoperative
      chemotherapy in patients with malignant bone and soft-tissue tumors.
AB  - PURPOSE: This study was aimed to determine whether Tc-99m-hexakis-2
      methoxyisobutylisonitrile (MIBI) scintigraphy performed in the middle of
      preoperative chemotherapy has a prognostic value in patients with malignant bone
      and soft tissue tumors (MBST). MATERIALS AND METHODS: In 90 patients with MBST,
      Tc-99m-MIBI scintigraphy was performed 15 minutes after tracer injection before
      the first and after the third chemotherapy cycles. After 5 cycles of chemotherapy
      and tumor resection, therapeutic effect was assessed by histopathology. The
      percent reduction of uptake ratio (DeltaUR) was calculated according to the
      following equation: 100 * ([prechemotherapy UR - post-middle course of
      chemotherapy UR]/prechemotherapy UR). RESULTS: The average follow-up for the
      entire population was 52 months. Twenty-one patients had clinically detectable
      metastases at initial presentation (primary metastasis). Kaplan-Meier analysis
      demonstrated that absence of metastasis was associated with good survival in all
      patients, in patients with bone tumor, and those with soft tissue tumor (P <
      0.0001, P < 0.0001, and P = 0.0003, respectively), and DeltaUR ?30% was also
      associated with survival in all patients and patients with bone tumor (P = 0.011
      and P = 0.047, respectively), but was marginal in those with soft tissue tumor (P
      = 0.091). Multivariate analysis showed that primary metastasis was the most
      powerful independent predictor of a lethal clinical outcome in all patients, in
      both patients with bone and soft tissue tumors (hazard ratio [HR]: 4.9, 95%
      confidence interval [CI]: 2.61-9.08, P < 0.0001; HR: 15.1, CI: 4.86-52.7, P <
      0.0001; HR: 3.7, CI: 1.45-8.94, P = 0.0069, respectively) and showed that Tc-99m
      MIBI scintigraphy had a good independent long-term prognostic value in all
      patients and patients with bone tumor (HR: 2.2, CI: 1.14-4.43, P = 0.017; HR:
      6.0, CI: 2.01-21.6, P = 0.0009, respectively) but not in those with soft tissue
      tumor (HR: 1.5, CI: 0.61-4.09, P = 0.38). Good disease-free survival was
      associated with DeltaUR ?30% in all patients and patients with soft tissue tumor
      (P = 0.0093 and P = 0.017, respectively) but not in those with bone tumor (P =
      0.19). CONCLUSIONS: Tc-99m-MIBI scintigraphy at the middle course of preoperative
      chemotherapy could be used as a prognostic indicator in patients with MBST.

PMID- 22157021
TI  - Lymphatic dysfunction in the apparently clinically normal contralateral limbs of
      patients with unilateral lower limb swelling.
AB  - PURPOSE: To determine how often lymphatic dysfunction is bilateral when,
      clinically, lymphedema appears unilateral. METHODS: Lymphoscintigraphy was
      performed after subcutaneous Tc-99m-nanocolloid injection in the first webspaces
      of both feet. The percentage of injected radioactivity accumulating in the
      ilioinguinal regions was recorded in dedicated images separately acquired at 60
      and 180 minutes after injection. RESULTS: Within a consecutive series of 204
      patients, 74 had unilateral clinical lymphedema of whom 68 had abnormal
      scintigraphy. Of these 68 patients, 46 had unilateral abnormal scintigraphy
      affecting the clinically abnormal limb, but 20 patients had bilateral abnormal
      scintigraphy and 2 had unilateral abnormal scintigraphy in the clinically
      unaffected limb. Thus, 32% (22/68) of patients in whom clinical lymphedema
      appeared to be unilateral, nevertheless, had abnormal scintigraphy in the
      clinically normal limb. Twenty-nine patients had no clinical evidence of
      lymphedema in either limb and were scintigraphically normal bilaterally. Mean
      ilioinguinal nodal accumulation at 180 minutes in the 44 limbs of 22 of these
      clinically and scintigraphically normal patients (dedicated ilioinguinal imaging
      was not performed in all patients) was 13.1% (standard deviation, 8.8%), higher
      (P = 0.02) than the mean value of 9.3% (standard deviation, 5.0%) in the
      clinically and scintigraphically normal contralateral limbs of 39 patients with
      unilateral clinical lymphedema. CONCLUSIONS: In the presence of unilateral
      lymphedema, the contralateral limb is often also abnormal. On lymphoscintigraphy,
      therefore, care should be taken before diagnosing unilateral lymphatic
      dysfunction. Quantification should be included in routine lymphoscintigraphy, as
      reduced ilioinguinal nodal accumulation may be the only apparent abnormality.

PMID- 22157022
TI  - The utility of two somatostatin analog radiopharmaceuticals in assessment of
      radiologically indeterminate pulmonary lesions.
AB  - PURPOSE: The aim of our study was to assess diagnostic accuracy of Tc-99m
      depreotide and Tc-99m-EDDA/HYNIC-TOC scintigraphy for evaluation of pulmonary
      lesions that appeared ambiguous on computed tomography (CT). MATERIAL AND
      METHODS: Forty-nine consecutive patients (37 men and 12 women; mean age, 60 +/-
      11 years) with 60 pulmonary lesions on chest radiography and CT were referred for
      nuclear imaging. They were prospectively allocated to undergo whole-body
      scintigraphy (WBS) and single photon emission computed tomography (SPECT) using
      either Tc-99m depreotide (26 patients, group 1) or Tc-99m-EDDA/HYNIC-TOC imaging
      (23 patients, group 2). Histologic findings after tissue biopsy served as a gold
      standard for determining diagnostic accuracy of the 2 somatostatin analogs.
      Visual assessment was complemented by semiquantitative analysis based on target
      to background ratio. RESULTS: Among the 32 pulmonary lesions scanned with Tc-99m
      depreotide, focal uptake was increased in 22 of 25 malignancies, whereas no
      uptake was found in 6 of 7 benign lesions (88% sensitivity, 85% specificity, and
      88% accuracy) on both WBS and SPECT. Imaging of 28 pulmonary lesions with Tc-99m
      EDDA/HYNIC-TOC had a similar diagnostic yield (sensitivity 87%, specificity 84%,
      and accuracy 86%). Overall, target to background ratios were higher on SPECT than
      WBS but not significantly different between groups 1 and 2 (SPECT 2.72 +/- 0.70
      vs. 2.71 +/- 0.50, WBS 1.61 +/- 0.32 vs. 1.62 +/- 0.28, respectively).
      CONCLUSION: This study demonstrates that Tc-99m depreotide and Tc-99m-EDDA/HYNIC
      TOC have similar diagnostic value for characterizing pulmonary lesions that
      appear ambiguous on CT.

PMID- 22157023
TI  - F-18 FDG PET/CT for detecting bone and bone marrow involvement in sarcoidosis
      patients.
AB  - BACKGROUND: The prevalence of bone involvement in sarcoidosis has been estimated
      to be 3% to 5%, mostly affecting the phalanges. The aim of this study was to
      assess the prevalence and distribution pattern of bone and bone marrow
      involvement as detected by positron emission tomography/computed tomography
      (PET/CT) in sarcoidosis patients. METHODS: Between June 2006 and September 2010,
      122 patients suffering from severe sarcoidosis who underwent a PET/CT and met the
      inclusion criteria were studied. In 94 (77%) patients, the PET/CT demonstrated
      positive findings associated with sarcoidosis. The 94 PET/CTs were screened for
      the presence of bone/bone marrow localizations. Additionally, low-dose CT scans
      were screened for other causes of increased bone uptake. Relevant clinical data
      were gathered retrospectively. RESULTS: Evidence for bone/bone marrow
      localizations was found in 34% of the 94 patients with PET/CT-positive findings.
      Of these patients, 60% showed obvious focal bone lesions at various
      localizations: axial skeleton (47%), pelvis (40%), extremities (34%), and skull
      (2%). In 40% of patients, diffuse increased uptake in both axial and peripheral
      bone marrow, without focal lesions, was found. Both diffuse and focal uptake were
      seen in 34%, whereas only focal lesions were observed in 25%. In all but 2 (6%)
      patients, no bone abnormalities on low-dose CT were found. CONCLUSIONS: More than
      one-third of PET/CT-positive sarcoidosis patients had osseous abnormalities on
      PET/CT. The majority of these lesions (94%) could not be detected on low-dose CT.
      No single localization of preference was found. These preliminary results stress
      the value of PET/CT imaging in the assessment of bone/bone marrow involvement in
      sarcoidosis patients.

PMID- 22157024
TI  - Clinical utility of SPECT-(low-dose)CT versus SPECT alone in patients presenting
      for bone scintigraphy.
AB  - PURPOSE: This prospective study evaluated the contribution of single-photon
      emission computed tomography (SPECT)-(low-dose)CT (SPECT-ldCT) over SPECT alone
      in all-comers referred for bone scintigraphy for any indication. METHODS: In this
      prospective study, imaging was performed on 100 consecutive patients who
      presented for bone scintigraphy using a combined SPECT-ldCT single-gantry system
      (Brightview XCT, Philips Medical Systems Inc., Cleveland, OH). SPECT images were
      reconstructed with (AC) and without (NAC) attenuation and scatter correction.
      SPECT (NAC), SPECT-ldCT (NAC), and SPECT-ldCT (AC) were reviewed independently
      and in a blinded manner. Reader interpretation of images was compared with the
      final clinical diagnosis. RESULTS: Subjects were referred for oncologic (28%) and
      nononcologic (72%) indications. Attenuation correction significantly improved
      perceived image quality (P = 0.012), but did not significantly alter diagnostic
      confidence (P = 0.96). Availability of ldCT data during interpretation of the
      SPECT images yielded a significant increase in the level of diagnostic confidence
      (P < 0.001). When the ldCT data were available, 18 of 200 bone SPECT reads
      recommended additional diagnostic CT imaging, compared with 70 when ldCT data
      were unavailable at the time of reading (P < 0.001). The sensitivity,
      specificity, and accuracy of SPECT-ldCT (with or without attenuation and scatter
      correction) in the diagnosis of osseous processes were 90.9%, 85.9%, and 87.0%,
      respectively, and these values did not differ significantly from those obtained
      with SPECT alone. CONCLUSIONS: Bone SPECT-ldCT provides interpreting physicians a
      significantly greater level of diagnostic confidence and reduces additional
      diagnostic imaging studies, but the overall diagnostic accuracy of SPECT-ldCT was
      not affected when compared with SPECT alone, suggesting that SPECT-ldCT should be
      used on a patient-by-patient basis.

PMID- 22157025
TI  - Smoking, dopamine transporter, and hand tremor.
AB  - AIM: The purpose of the study was to evaluate the relationship between the number
      of packs smoked per day and specific uptake ratio (SUR) in the striatum on Tc-99m
      TRODAT, and frequency of hand tremor. METHODS: It was a prospective, cross
      sectional study. In all, 23 healthy nonsmokers and 37 current smokers were
      recruited in the study. All subjects underwent Tc-99m TRODAT SPECT, brain CT
      scan, thyroid function test, tremor measurement system, and neurologic
      examinations. RESULTS: There were significant differences in the SUR in the
      striatum on Tc-99m TRODAT and in the frequency of hand tremor in rest state and
      in arm extended state among nonsmokers (grade I), current smokers with less than
      1 pack smoked per day (grade II), and current smokers with equal or more than 1
      pack smoked per day (grade III) by ANOVA (all P < 0.001). After adjusting for age
      and gender, there was a significantly negative correlation between smoke grade
      and SUR in the striatum on Tc-99m TRODAT by multiple linear regression (beta = 
      0.45, P < 0.001). Smoke grade was the significant predictor for the frequency of
      hand tremor in rest state and in arm extended state, after adjusting for age and
      gender by multiple linear regression (beta = 14.70, P < 0.001; beta = 15.37, P <
      0.001). CONCLUSIONS: There is a dose-response relationship between the number of
      packs smoked per day and SUR in the striatum, and the frequency of hand tremor.
      Decreased dopamine transporter binding in the striatum and increased frequency of
      hand tremor in smokers may have important implications for evaluating the impact
      of smoking on the central and peripheral nerve systems.

PMID- 22157026
TI  - Utility of F-18 FDG PET/CT in screening for paraneoplastic neurological
      syndromes.
AB  - PURPOSE: The aim of this study was to assess the utility of positron emission
      tomography/computed tomography (PET/CT) for the investigation of patients with
      suspected paraneoplastic neurologic syndrome (PNS). MATERIALS AND METHODS: We
      reviewed the whole-body fluorodeoxyglucose (FDG) PET/CT studies (ordered by the
      neurology department) performed at our hospital between December 2005 and
      November 2010; 27 cases (16 men, 11 women; mean age, 65 years) who were suspected
      of having PNS were selected. RESULTS: Of the 27 patients, 6 (22%) had an abnormal
      FDG uptake. Of these 6 patients, 5 (19%) were histologically confirmed as having
      a malignancy. Of the 27 patients, 7 were tested for the presence of well
      characterized paraneoplastic antibodies (anti-Hu, anti-Ri, anti-Yo); 1 had anti
      Hu, but the patient did not have an abnormal FDG uptake or malignancy.
      CONCLUSIONS: PET/CT may be a useful screening tool for patients with clinically
      suspected PNS who do not exhibit well-characterized paraneoplastic antibodies.
      Therefore, we recommended that PET/CT should be performed for patients with
      clinically suspicious PNS regardless of the presence of well-characterized
      paraneoplastic antibodies.

PMID- 22157027
TI  - The role of myocardial viability assessed by perfusion/F-18 FDG imaging in
      children with anomalous origin of the left coronary artery from the pulmonary
      artery.
AB  - PURPOSE: Although surgical treatments evolved, the short-term postoperative
      mortality is still high in children with anomalous origin of the left coronary
      artery from the pulmonary artery (ALCAPA), and long-term survivors may suffer
      from restrained functional recovery. Therefore, an optimal means in predicting
      postoperative reversal is demanded. In this study, we assess the utility of
      myocardial perfusion/F-18 fluorodeoxyglucose (FDG) imaging in the evaluation of
      myocardial viability and postsurgery functional recovery in children with ALCAPA.
      MATERIALS AND METHODS: A retrospective study was performed in 7 children with
      diagnosed ALCAPA who underwent myocardial perfusion/F-18 FDG imaging
      preoperatively. Global viability index was used to evaluate myocardial viability
      and was compared with the preoperative deviations of left ventricular ejection
      fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) from age
      matched healthy children and with the postoperative durations of intensive care.
      RESULTS: Children with more viable myocardium had less severe clinical symptoms.
      The viability index was correlated well with the preoperative deviations of LVEF
      (r = -0.98, P = 0.001) and LVEDD (r = 0.87, P = 0.02) and postoperative durations
      of intensive care hospitalization (r = 0.77, P = 0.04) and mechanical ventilation
      (r = 0.83, P = 0.02). LVEF and LVEDD reached normal range within 5 months in
      viable children, whereas incomplete reversal was observed in partial- and
      nonviable children. CONCLUSIONS: In children with ALCAPA, myocardial viability
      evaluated by perfusion/F-18 FDG imaging is related to the preoperative clinical
      manifestations and cardiac function. Additionally, it may predict functional
      recovery after surgical repair.

PMID- 22157028
TI  - Relationship among glycolytic phenotype, grade, and histological subtype in
      ovarian carcinoma.
AB  - PURPOSE: Knowing the glycolytic phenotype of cancers is important for the
      appropriate use of F-18 FDG PET/CT imaging. This study was performed to determine
      the influence of tumor grade and histology on the glycolytic phenotype of
      epithelial ovarian cancer patients. MATERIALS AND METHODS: Only
      histopathologically confirmed epithelial ovarian cancer patients, with no other
      concurrent malignancies, who had F-18 FDG PET/CT either before or at least 3
      months after any therapeutic intervention and had confirmed measurable disease of
      >1 cm were included. The F-18 FDG PET/CT uptake was determined as maximum
      standard uptake value (SUVmax) at the pathologically confirmed site of disease or
      in the most active lesion. SUVmax was correlated to tumor grade and histology.
      RESULTS: Of 171 ovarian cancer patients, 42 referred for F-18 FDG PET/CT scans
      between January 2003 and December 2010 were eligible for inclusion. Histologic
      diagnosis most frequently revealed the serous subtype (n = 32) and grade III (n =
      28) epithelial ovarian cancer. Overall, ovarian carcinomas exhibited a strong
      glycolytic phenotype (average SUVmax, 7.6 g/mL). The SUVmax averaged 7.76 g/mL,
      6.76 g/mL, and 7.95 g/mL for Grade I, II, and III, respectively. There was no
      statistically significant correlation between tumor SUVmax and the histologic
      tumor grade (P = 0.74). No statistically significant differences were found
      between the tumor SUVmax of serous and endometrioid subtypes (P = 0.53). For
      other histology subtypes, no statistic evaluation was possible due to the low
      number of cases. CONCLUSIONS: The glycolytic phenotype in epithelial ovarian
      cancer, expressed as SUVmax, is strong. However, tumor FDG uptake is unrelated to
      tumor grade and histologic subtype implying that F-18 FDG PET/CT cannot be used
      to predict tumor aggressiveness or histology.

PMID- 22157029
TI  - FDG PET/CT in ovarian cancer: what about treatment response and prognosis?

PMID- 22157030
TI  - Ga-68 DOTA-NOC uptake in the pancreas: pathological and physiological patterns.
AB  - OBJECTIVE: Gallium-68 (Ga-68) DOTA-1-NaI3-octreotide (DOTA-NOC) positron emission
      tomography (PET)/computed tomography (CT) is increasingly used for neuroendocrine
      tumors (NETs), often found primarily in the pancreas. However, physiologic uptake
      of DOTA-NOC has been described in the uncinate process of the pancreas. We
      studied DOTA-NOC uptake in this organ. MATERIALS AND METHODS: Ninety-six patients
      underwent 103 DOTA-NOC scans, with pathology-proven pancreatic NET (n = 40) and
      nonpancreatic NET or biochemical suspicion of NET (n = 63). RESULTS: DOTA-NOC
      uptake was detected in 35 documented pancreatic tumor sites (SUV: 5.5-165; mean:
      25.7 +/- 28.8; median: 17.8). Among 63 cases without previous known pathology,
      uptake was suspicious for tumor in 24 sites (SUV: 4.7-35; mean 16.3 +/- 8.0;
      median: 14.1), and in 38 sites, it was judged as physiological, generally lower
      relative to adjacent structures (SUV: 2.2-12.6; mean: 6.6 +/- 2.2; median: 6.2).
      In 24 scans with suspected tumor and in 37 of 38 scans with physiological uptake,
      diagnostic computed tomography or magnetic resonance imaging or endoscopic
      ultrasonography failed to detect tumor. CONCLUSIONS: Pancreatic DOTA-NOC uptake
      must be interpreted with caution, and further studies are required.

PMID- 22157031
TI  - Cholecystokinin-cholescintigraphy in adults:  consensus recommendations of an
      interdisciplinary panel.
AB  - BACKGROUND AND AIMS: Cholecystokinin-cholescintigraphy (CCK-CS) provides a
      physiologic, noninvasive, and quantitative method for assessing gallbladder
      contraction and calculation of a gallbladder ejection fraction (GBEF). At
      present, it is used most commonly to identify patients with suspected functional
      gallbladder disorder. However, the methodology of CCK infusion and normal values
      differ markedly among imaging centers. METHODS: This document represents the
      consensus opinion of an interdisciplinary panel that gathered to assess the
      current optimal method for performing CCK-CS in adults, potential uses and
      limitations of CCK-CS, and questions that require further investigation. RESULTS:
      The panel recommended the use of a single, standardized, recently described CCK
      CS protocol that involves infusion of 0.02 MUg/kg of sincalide over 60 minutes
      with a normal GBEF defined as >=38%. The panel emphasized the need for a large,
      multicenter, prospective clinical trial to establish the utility of CCK-CS in the
      diagnosis of functional gallbladder disease. Although not without controversy
      regarding its clinical utility, the primary indication for CCK-CS at present is
      the well-selected patient with suspected functional gallbladder disorder.
      CONCLUSION: Agreement was reached that the adoption of this standardized protocol
      is critical to improve how CCK-CS is used to direct patient care and will
      represent an improvement over the diverse methods currently in use by eliminating
      the current lack of uniformity and adding both reliability and credibility to the
      results.

PMID- 22157032
TI  - Planning and conducting meetings effectively, part II: Some component aspects of
      a meeting.
AB  - There are many components of a decision-making meeting. The role of the
      chairperson, important aspects of how to begin a meeting, the technique of
      brainstorming, and follow-up after a meeting are described in this article.

PMID- 22157033
TI  - Lymphoma in a case of Shwachman-Diamond syndrome: PET/CT findings.

PMID- 22157034
TI  - Craniopharyngioma with high FDG uptake.

PMID- 22157035
TI  - Macroaggregated albumin injected in hepatic artery visualized in a recanalized
      paraumbilical vein.

PMID- 22157036
TI  - Dicyclomine:  cause of abnormally decreased gall bladder ejection with sincalide
      stimulated hepatobiliary scintigraphy.

PMID- 22157037
TI  - Bronchial atresia on FDG PET/CT: imaging characteristics of a rare pulmonary
      pseudonodule.

PMID- 22157038
TI  - Benign epithelial cyst mimicking thyroid cancer metastasis: a false-positive
      finding on post-therapy I-131 scan.

PMID- 22157039
TI  - F-18 FDG uptake in hemorrhoids in a patient with diffuse large B-cell lymphoma.

PMID- 22157040
TI  - Intrathoracic renal ectopia mimicking CSF leakage on radionuclide cisternography
      demonstrated by SPECT/CT.

PMID- 22157041
TI  - FDG PET/CT of bilateral testicular lymphoma.

PMID- 22157042
TI  - Nontargeted Y-90 microsphere radioembolization to duodenum visualized on Y-90
      PET/CT and Bremsstrahlung SPECT/CT.

PMID- 22157043
TI  - Subcutaneous injection of the HIV-1 fusion inhibitor enfuvirtide (FUZEON) may
      result in soft-tissue accumulation of Tc-99m MDP.

PMID- 22157044
TI  - Neoadjuvant downsizing by internal radiation: a case for preoperative peptide
      receptor radionuclide therapy in patients with pancreatic neuroendocrine tumors.

PMID- 22157045
TI  - Identification of the falciform artery on nuclear medicine imaging with
      successful coil embolization for planned Y-90 therapy.

PMID- 22157046
TI  - Hypertrophic cranial pachymeningitis with IgG4-positive plasma cells detected by
      C-11 methionine PET.

PMID- 22157047
TI  - A pitfall of C-11 methionine PET: cerebral venous infarction mimicked a glioma.

PMID- 22157048
TI  - Current readings in nuclear medicine.

PMID- 22157049
TI  - F-18 choline PET does not detect increased metabolism in F-18 fluoroethyltyrosine
      negative low-grade gliomas.
AB  - PURPOSE: Positron emission tomography (PET) with radiolabeled amino acids
      provides information on biopsy target and chemotherapy response in patients with
      low-grade gliomas (LGG). In this article, we addressed whether PET with F-18
      choline (CHO) detects increased metabolism in F-18 fluoroethyltyrosine (FET)
      negative LGG patients. METHODS: Six LGG patients with nongadolinium-enhancing
      (magnetic resonance) FET-negative LGG were imaged with CHO PET. Regions of
      interest were positioned over tumor and contralateral brain. Uptake of FET and
      CHO was quantified as count ratio of tumor to contralateral brain. RESULTS: The
      mean FET uptake ratio for FET-negative LGG was 0.95 +/- 0.03 (mean +/- standard
      deviation). Five tumors did not show increased uptake ratios for CHO (0.96 +/-
      0.12). Slightly increased CHO uptake was found in 1 patient (1.24), which,
      however, was not associated with tumor visualization. CONCLUSIONS: Amino acid and
      choline uptake appear to behave similar in nongadolinium-enhancing LGG. For
      clinical purposes, CHO PET is not superior to FET PET.

PMID- 22157050
TI  - Pain-related F-18 FDG uptake of the corrugator supercilii muscles in PET/CT.

PMID- 22157051
TI  - Quantitative Evaluation of incomplete embolization in a patient with
      portosystemic shunt by per-rectal portal scintigraphy.

PMID- 22157052
TI  - Protein-losing gastropathy in peritoneal dialysis as a wolf in sheep's clothing:
      Tc-99m human serum albumin SPECT/CT diagnosis.

PMID- 22157053
TI  - Acute appendicitis secondary to metastatic small cell lung cancer incidentally
      found on F-18 FDG PET/CT.

PMID- 22157054
TI  - F-18 fluoride uptake in calcified extraosseous metastases from ovarian papillary
      serous adenocarcinoma.

PMID- 22157055
TI  - Epileptogenic pachygyria demonstrating on FDG PET.

PMID- 22157056
TI  - Lymphoscintigraphy revealed abnormal lymphatic drainage in chyloperitoneum.

PMID- 22157057
TI  - Cytokeratin expression in gastrointestinal stromal tumor:  a clinicopathologic
      and immunohistochemical study of 687 cases.
AB  - Gastrointestinal stromal tumor is the most common clinically significant
      mesenchymal neoplasm of the gastrointestinal tract. The expression of the
      intermediate filament cytokeratin in gastrointestinal stromal tumor is not
      frequently reported in the literature. The aim of this study was to investigate
      the immunohistochemical expression of several types of cytokeratin in a large
      number of cases (n=687), including a pan-cytokeratin marker (AE1/AE3 cocktail
      antibodies), high-molecular weight cytokeratins (34betaE12 antibody), and
      individual cytokeratins 8 (35betaH11 and CAM5.2 antibodies), 7, 14, and 20. Ki-67
      antigen was used for the determination of cell proliferation index, and the
      correlation between Ki-67 and cytokeratin expression was evaluated. Cytokeratin
      expression was also correlated with several clinicopathologic parameters. The
      expression of pan-cytokeratin was observed in 24 (3.5%) cases, with variable
      intensity. Only 1 of 687 (0.1%) cases showed cytokeratin 14 expression. All 687
      cases revealed no expression of high-molecular weight cytokeratins, cytokeratins
      7, 8, and 20. No significant statistical association was found between AE1/AE3
      immunoreactivity and several clinicopathologic parameters, including sex, tumor
      location and size, cell morphology, mitotic count, risk of aggressive behavior,
      and Ki-67 antigen cell proliferation index. However, statistical correlation
      between AE1/AE3 immunoreactivity and a higher age at diagnosis was detected.
      These results show that cytokeratin expression is not frequent in
      gastrointestinal stromal tumor, but caution is necessary to avoid erroneous
      diagnoses.

PMID- 22157058
TI  - Ghrelin immunoexpression in the human hypophysis.
AB  - The aim of this study was to immunohistochemically localize ghrelin in autopsy
      obtained, nontumoral human pituitaries. Double immunostaining was also undertaken
      to determine the pituitary cell type expressing both adenohypophysial hormones
      and ghrelin. Results showed that ghrelin is present in the adenohypophysis, its
      immunoexpression being cytoplasmic, weak-to-moderate, and localized to a subset
      of cells. Double immunostaining showed that ghrelin is present in 51% to 90% of
      growth hormone-producing, luteinizing-producing, and alpha-subunit-producing
      cells. Ghrelin immunoexpression was less frequently observed in other
      adenohypophysial cell types, being seen in 30% of adrenocorticotropin and
      follicle-stimulating hormones, 15% of thyrotropin, and 10% of prolactin
      immunoreactive cells. Ghrelin immunopositivity was also seen in nerve fibers and
      Herring bodies of the neurohypophysis and pituitary stalk. More work is needed to
      elucidate the role of ghrelin in adenohypophysial and neurohypophysial endocrine
      activity. It may well be that ghrelin exerts an autocrine/paracrine effect and
      can modulate hormone synthesis and release.

PMID- 22157059
TI  - Automatic nonsubjective estimation of antigen content visualized by
      immunohistochemistry using color deconvolution.
AB  - We describe a method for the automatic, nonsubjective estimation of 3,3'
      diaminobenzidine (DAB) in digital images obtained from routine central nervous
      system immunohistochemistry using freely available, platform-independent public
      domain image processing software. This technique estimates the amount of antigen
      visualized but does not measure antigen content directly. Combined with whole
      brain section high-resolution scanning, a "virtual dissection" (extracting the
      region of interest) makes it possible to estimate relative antigen content in
      either subcellular structures, specific brain regions, or in whole tissue
      sections at magnifications up to 40*. The digital image is processed using
      Ruifrok and Johnston's color deconvolution method to separate the brown DAB
      chromogen from the hematoxylin counterstain on a microscope slide. A monochrome
      image representing the DAB content is then subjected to frequency analysis using
      NIH-ImageJ and a weighting calculation to estimate the amount of DAB (antigen) as
      a dimensionless index. The method described produces results that agree with
      enzyme-linked immunosorbent assays, and is automatic and nonsubjective. The
      method could easily be adapted to other types of tissue or cell cultures.

PMID- 22157060
TI  - The glycemic index issue.
AB  - PURPOSE OF REVIEW: In recent years, many of the concerns surrounding the glycemic
      index have been addressed by methodological studies and clinical trials comparing
      diets carefully matched for other nutrients. These findings are reviewed together
      with new observational evidence for the role of the dietary glycemic index in the
      etiology of cardiovascular disease. RECENT FINDINGS: The determination and
      classification of the glycemic index of a food product is now standardized by the
      International Standards Organization. Systematic studies using isoenergetic
      single and mixed meals have shown that glycemic index and/or glycemic load are
      stronger predictors of postprandial glycemia and insulinemia than carbohydrate
      content alone. In overweight individuals, a diet that combined modestly higher
      protein and lower glycemic index carbohydrates was the most effective diet for
      prevention of weight regain. New observational studies have reported increased
      risks of coronary heart disease associated with higher intakes of carbohydrates
      from high glycemic index foods. Epidemiological evidence has emerged linking
      dietary glycemic index to visceral fat and inflammatory disease mortality.
      SUMMARY: There is growing recognition that replacing saturated fat with refined,
      high glycemic index carbohydrates increases postprandial glycemia and may be
      detrimental for weight control and predisposition to cardiovascular and
      inflammatory disease. In contrast, low glycemic index carbohydrates reduce risk.

PMID- 22157061
TI  - Mobile medical visual information retrieval.
AB  - In this paper, we propose mobile access to peer-reviewed medical information
      based on textual search and content-based visual image retrieval. Web-based
      interfaces designed for limited screen space were developed to query via web
      services a medical information retrieval engine optimizing the amount of data to
      be transferred in wireless form. Visual and textual retrieval engines with state
      of-the-art performance were integrated. Results obtained show a good usability of
      the software. Future use in clinical environments has the potential of increasing
      quality of patient care through bedside access to the medical literature in
      context.

PMID- 22157062
TI  - Abnormality segmentation in brain images via distributed estimation.
AB  - The aim of this paper is to introduce a novel semisupervised scheme for
      abnormality detection and segmentation in medical images. Semisupervised learning
      does not require pathology modeling and, thus, allows high degree of automation.
      In abnormality detection, a vector is characterized as anomalous if it does not
      comply with the probability distribution obtained from normal data. The
      estimation of the probability density function, however, is usually not feasible
      due to large data dimensionality. In order to overcome this challenge, we treat
      every image as a network of locally coherent image partitions (overlapping
      blocks). We formulate and maximize a strictly concave likelihood function
      estimating abnormality for each partition and fuse the local estimates into a
      globally optimal estimate that satisfies the consistency constraints, based on a
      distributed estimation algorithm. The likelihood function consists of a model and
      a data term and is formulated as a quadratic programming problem. The method is
      applied for automatically segmenting brain pathologies, such as simulated brain
      infarction and dysplasia, as well as real lesions in diabetes patients. The
      assessment of the method using receiver operating characteristic analysis
      demonstrates improvement in image segmentation over two-group analysis performed
      with Statistical Parametric Mapping (SPM).

PMID- 22157063
TI  - Imaging and uncertainty in the use of lumbar epidural steroid injections: comment
      on "effect of MRI on treatment results or decision making in patients with
      lumbosacral radiculopathy referred for epidural steroid injections".

PMID- 22157064
TI  - Maintaining planned readmissions.

PMID- 22157065
TI  - Young-onset colorectal cancer: is it time to pay attention?

PMID- 22157066
TI  - Planned readmissions: a potential solution.

PMID- 22157067
TI  - Effect of MRI on treatment results or decision making in patients with
      lumbosacral radiculopathy referred for epidural steroid injections: a
      multicenter, randomized controlled trial.
AB  - BACKGROUND: Studies have shown that radiologic imaging does not improve outcomes
      in most patients with back pain, though guidelines endorse it before epidural
      steroid injections (ESIs). The objective of this study was to determine whether
      magnetic resonance imaging (MRI) improves outcomes or affects decision making in
      patients with lumbosacral radiculopathy referred for ESI. METHODS: In this
      multicenter randomized study, the treating physician in group 1 patients was
      blinded to the MRI results, while the physician for group 2 patients decided on
      treatment after reviewing the MRI findings. In group 1 subjects, an independent
      physician proposed a treatment plan after reviewing the MRI, which was compared
      with the treatment the patient received. RESULTS: Slightly lower leg pain scores
      were noted in the group 2 at 1 month compared with MRI-blinded patients in group
      1 (mean scores, 3.6 vs 4.4) (P = .12). No differences were observed in pain
      scores or function at 3 months. Overall, the proportion of patients who
      experienced a positive outcome was similar at all time points (35.4% at 3 months
      in group 1 vs 40.7% in group 2). Among subjects in group 1 who received a
      different injection than that proposed by the independent physician, scores for
      both leg pain (4.8 vs 2.4) (P = .01) and function (38.7 vs 28.2) (P = .04) were
      inferior to patients whose injection correlated with imaging. Collectively, 6.8%
      of patients did not (group 2) or would not have (group 1) received an ESI after
      the MRI was reviewed. CONCLUSION: Magnetic resonance imaging does not improve
      outcomes in patients who are clinical candidates for ESI and has only a minor
      effect on decision making. Trial Registration clinicaltrials.gov Identifier:
      NCT00826124.

PMID- 22157068
TI  - Nocturnal leg cramps and prescription use that precedes them: a sequence symmetry
      analysis.
AB  - BACKGROUND: The use of diuretics, statins, and inhaled long-acting beta2-agonists
      (LABAs) is linked to muscle cramps but largely by anecdotal evidence. This study
      sought population-level data to better evaluate these associations. METHODS:
      Linked health care databases containing prescribing information (December 1,
      2000, to November 30, 2008) about 4.2 million residents of British Columbia,
      Canada, were evaluated using sequence symmetry analysis to determine in adults 50
      years or older whether new quinine prescriptions (initiations of cramp treatment)
      increase in the year following diuretic, statin, or LABA starts. The statistic of
      interest was the sequence ratio: the number of quinine starts in the year
      following index drug introduction compared with the number of quinine starts in
      the preceding year (adjusted for age and time trends in population prescribing).
      RESULTS: Adjusted sequence ratios (95% CIs) for the 3 drug classes were 1.47
      (1.33-1.63 [P < .001]) for diuretics, 1.16 (1.04-1.29 [P = .004]) for statins,
      and 2.42 (2.02-2.89 [P < .001]) for LABAs. For diuretic subclasses, adjusted
      sequence ratios (95% CIs) were 2.12 (1.61-2.78 [P < .001]) for potassium sparing,
      1.48 (1.29-1.68 [P < .001]) for thiazidelike, and 1.20 (1.00-1.44 [P = .07]) for
      loop. For LABA subclasses, adjusted sequence ratios (95% CIs) were 2.17 (1.56
      3.02) for LABAs alone and 2.55 (2.06-3.12) for LABAs-corticosteroids (P < .001
      for both). CONCLUSIONS: Cramp treatment was substantially more likely in the year
      following introduction of LABAs, potassium-sparing diuretics, or thiazidelike
      diuretics, and 60.3% of quinine users (individuals experiencing cramp) received
      at least 1 of these medications during a 13-year period. In contrast, statin and
      loop diuretic associations were small. Physicians should be mindful that the use
      of these medications may worsen symptoms in patients experiencing nocturnal leg
      cramps.

PMID- 22157069
TI  - Fertility, sexuality and testicular adrenal rest tumors in adult males with
      congenital adrenal hyperplasia.
AB  - OBJECTIVE: Fertility in males with congenital adrenal hyperplasia (CAH) is
      reported from normal to severely impaired. Therefore, we investigated
      fertility/fecundity, social/sexual situation, and pituitary-gonadal function in
      CAH males. SUBJECTS AND METHODS: The patient cohort comprised 30 males, aged 19
      67 years, with 21-hydroxylase deficiency. Their fertility was compared with age
      matched national population data. For the evaluation of social/sexual factors and
      hormone status, age-matched controls were recruited (n = 32). Subgroups of
      different ages (<30 years and older) and CYP21A2 genotypes (null (severe salt
      wasting (SW)), I2splice (milder SW), and I172N (simple virilizing)) were also
      studied. Patients underwent testicular ultrasound examination (n = 21) and semen
      analysis (n = 14). RESULTS: Fertility was impaired in CAH males compared with
      national data (0.9 +/- 1.3 vs 1.8 +/- 0.5 children/father, P<0.001). There were
      no major differences in social and sexual factors between patients and controls
      apart from more fecundity problems, particularly in the I172N group. The patients
      had lower testosterone/estradiol (E(2)) ratio and inhibin B, and higher FSH. The
      semen samples were pathological in 43% (6/14) of patients and sperm concentration
      correlated with inhibin B and FSH. Testicular adrenal rest tumors (TARTs) were
      found in 86% (18/21). Functional testicular volume correlated positively with the
      testosterone/E(2) ratio, sperm concentration, and inhibin B. Patients with
      pathological semen had increased fat mass and indications of increased
      cardiometabolic risk. CONCLUSIONS: Fertility/fecundity was impaired in CAH males.
      The frequent occurrence of TARTs resulting in testicular insufficiency appears to
      be the major cause, but other factors such as elevated fat mass may contribute to
      a low semen quality.

PMID- 22157070
TI  - Toward automating Hammersmith pulled-to-sit examination of infants using feature
      point based video object tracking.
AB  - Hammersmith Infant Neurological Examination (HINE) is a set of tests used for
      grading neurological development of infants on a scale of 0 to 3. These tests
      help in assessing neurophysiological development of babies, especially preterm
      infants who are born before (the fetus reaches) the gestational age of 36 weeks.
      Such tests are often conducted in the follow-up clinics of hospitals for grading
      infants with suspected disabilities. Assessment based on HINE depends on the
      expertise of the physicians involved in conducting the examinations. It has been
      noted that some of these tests, especially pulled-to-sit and lateral tilting, are
      difficult to assess solely based on visual observation. For example, during the
      pulled-to-sit examination, the examiner needs to observe the relative movement of
      the head with respect to torso while pulling the infant by holding wrists. The
      examiner may find it difficult to follow the head movement from the coronal view.
      Video object tracking based automatic or semi-automatic analysis can be helpful
      in this case. In this paper, we present a video based method to automate the
      analysis of pulled-to-sit examination. In this context, a dynamic programming and
      node pruning based efficient video object tracking algorithm has been proposed.
      Pulled-to-sit event detection is handled by the proposed tracking algorithm that
      uses a 2-D geometric model of the scene. The algorithm has been tested with
      normal as well as marker based videos of the examination recorded at the neuro
      development clinic of the SSKM Hospital, Kolkata, India. It is found that the
      proposed algorithm is capable of estimating the pulled-to-sit score with
      sensitivity (80%-92%) and specificity (89%-96%).

PMID- 22157071
TI  - Preoperative treatment with levosimendan in candidates for mechanical circulatory
      support.
AB  - Left ventricular assist device (LVAD) implantation is a widely accepted treatment
      for end-stage heart failure. Preoperative conditions and right ventricular
      dysfunction are determinant parameters that influence outcome. We investigated
      the effect of preoperative levosimendan treatment in LVAD patients with moderate
      right ventricular dysfunction and right ventricular dilatation. Twenty-one
      patients treated with LVADs were included in the study. Before surgery, patients
      received levosimendan infusion (0.1-0.2 MUg/kg/min) for 48 hours. Hemodynamic
      parameters and NT-proBNP were evaluated before, during, and 24 hours after the
      end of levosimendan treatment. During levosimendan treatment, all patients
      demonstrated a significant improvement in cardiac index (p = 0.014), pulmonary
      pressure (p = 0.003), and central venous pressure (p = 0.016). The hemodynamic
      condition worsened 24 hours after the end of the treatment in patients who died
      because of right ventricular failure while it was s in patients who survived. NT
      proBNP was significantly higher (6733 vs. 8797 pg/ml) (p = 0.019) in patients who
      died because of right ventricular failure after 24 hours of levosimendan
      treatment. During levosimendan treatment, the median NT-proBNP value in patients
      who survived decreased by 39%, whereas in patients who died there was an increase
      of 3% (p = 0.008) at 72 hours. A reduction in NT-proBNP to below 25% is a
      predictor of mortality with sensitivity of 100% and specificity of 70%.
      Levosimendan treatment improves preimplant hemodynamic performance and permits
      the identification of patients who will develop right ventricular failure.

PMID- 22157072
TI  - A novel technique for hepatic progenitor cell isolation from normal adult rat
      livers.
AB  - The transplantation of hepatic progenitor cells (HPCs) is a promising alternate
      approach to liver transplantation for patients with end-stage liver disease.
      Here, we report a novel technique for HPCs isolation from normal adult rat livers
      (no preexposure to chemicals and no injury). HPCs were isolated from normal adult
      rat livers using a novel four-step collagenase perfusion method followed by
      density gradient centrifugation. The phenotypic properties of HPCs were
      characterized by morphological observation, reverse-transcription polymerase
      chain reaction (RT-PCR), and immunocytochemistry. The results showed that HPCs
      formed loose colonies and possessed a round or oval shape at culture day 3. These
      cells proliferated slowly and exhibited progenitor-like characteristics during
      the 30-day culture period. RT-PCR analysis indicated that the cultured cells were
      positive for several HPC-specific genes, such as albumin (ALB), alpha-fetoprotein
      (AFP), cytokeratin 18 (CK18), cytokeratin 19 (CK19), CD45, hepatocyte nuclear
      factor 1-alpha (HNF-1alpha), hepatocyte nuclear factor 4-alpha (HNF-4alpha), and
      Thy-1. Immunocytochemical staining showed that these cells were consistently
      positive for ALB, AFP, CK18, CK19, Thy-1, and OV-6. HPCs can be isolated from
      normal adult rat livers using a simple and effective technique involving four
      step collagenase perfusion, further confirming their potential as a strong
      candidate for hepatocyte therapy.

PMID- 22157073
TI  - Chronic in vivo testing of the Penn State infant ventricular assist device.
AB  - The Penn State Infant Ventricular Assist Device (VAD) is a 12-14 ml stroke volume
      pneumatically actuated pump, with custom Bjork-Shiley monostrut valves, developed
      under the National Heart, Lung, and Blood Institute Pediatric Circulatory Support
      program. In this report, we describe the seven most recent chronic animal studies
      of the Infant VAD in the juvenile ovine model, with a mean body weight of 23.5 +/
      4.1 kg. The goal of 4-6 weeks survival was achieved in five of seven studies,
      with support duration ranging from 5 to 41 days; mean 26.1 days. Anticoagulation
      was accomplished using unfractionated heparin, and study animals were divided
      into two protocol groups: the first based on a target activated partial
      thromboplastin time of 1.5-2 times normal, and a second group using a target
      thromboelastography R-time of two times normal. The second group required
      significantly less heparin, which was verified by barely detectable heparin
      activity (anti-Xa). In both groups, there was no evidence of thromboembolism
      except in one animal with a chronic infection and fever. Device thrombi were
      minimal and were further reduced by introduction of the custom valve. These
      results are consistent with results of adult VAD testing in animals and are
      encouraging given the extremely low levels of anticoagulation in the second
      group.

PMID- 22157074
TI  - Magnetic nanoparticles for magnetoresistance-based biodetection.
AB  - Magnetic nanoparticles (MNPs) have been studied widely as a powerful diagnostic
      probe and therapeutic agent for biomedical applications. In recent years, they
      are also found to be sensitive to magnetoresistive (MR) devices and MNP-MR
      biochips are predicted to be more affordable, portable and sensitive than the
      conventional optical detection methods. In this MNP-MR biochip design, MNP probes
      are required to have high magnetic moment, high susceptibility, and be target
      specific. This review summarizes recent advances in chemical syntheses and
      functionalization of MNPs with controlled magnetic properties for sensitive MR
      detection and for bio-sensing applications.

PMID- 22157075
TI  - Comparative analysis of genomic signal processing for microarray data clustering.
AB  - Genomic signal processing is a new area of research that combines advanced
      digital signal processing methodologies for enhanced genetic data analysis. It
      has many promising applications in bioinformatics and next generation of
      healthcare systems, in particular, in the field of microarray data clustering. In
      this paper we present a comparative performance analysis of enhanced digital
      spectral analysis methods for robust clustering of gene expression across
      multiple microarray data samples. Three digital signal processing methods: linear
      predictive coding, wavelet decomposition, and fractal dimension are studied to
      provide a comparative evaluation of the clustering performance of these methods
      on several microarray datasets. The results of this study show that the fractal
      approach provides the best clustering accuracy compared to other digital signal
      processing and well known statistical methods.

PMID- 22157076
TI  - Inhibitory activity of Fe(3) O(4)/oleic acid/usnic acid-core/shell/extra-shell
      nanofluid on S. aureus biofilm development.
AB  - Undesired biofilm development is a major concern in many areas, especially in the
      medical field. The purpose of the present study was to comparatively investigate
      the antibiofilm efficacy of usnic acid, in soluble versus nanofluid formulation,
      in order to highlight the potential use of  Fe(3) O(4)/oleic  acid (FeOA)
      nanofluid as potential controlled release vehicle of this antibiofilm agent. The 
      (+) -UA loaded into nanofluid exhibited an improved antibiofilm effect on S.
      aureus biofilm formation, revealed by the drastic decrease of the viable cell
      counts as well as by confocal laser scanning microscopy images. Our results
      demonstrate that FeOA nanoparticles could be used as successful coating agents
      for obtaining antibiofilm pellicles on different medical devices, opening a new
      perspective for obtaining new antimicrobial and antibiofilm surfaces, based on
      hybrid functionalized nanostructured biomaterials.

PMID- 22157077
TI  - Stability and bifurcation analysis of models for zebrafish somitogenesis.
AB  - Notch-Delta signaling is indispensable for somitogenesis, which controls the
      vertebrate segmentation during embryonic development. Several theoretical models
      have been proposed to explain this interesting process. In zebrafish
      somitogenesis, genes her1, her7, delta, and their proteins plays the important
      roles. However, an auto-repression model with time delay involved only by
      her1/her7 is able to explain zebrafish somitogenesis. This paper will
      systematically study the dynamics of this model. Specifically we investigate its
      stability, bifurcation (oscillation), and stability of oscillation. First, the
      conditions for both stability and bifurcation are presented based on the
      linearized model. Then three indices for bifurcation of this nonlinear model are
      derived by using linear functional operator analysis. Finally, the numerical
      simulations are carried out to illustrate the theoretical results developed in
      this study.

PMID- 22157078
TI  - Fourier-bessel series modeling of dielectrophoretic bionanoparticle transport:
      principles and applications.
AB  - Principles and applications are described for a Fourier-Bessel series model that
      predicts the transport of bionanoparticles driven by a dielectrophoretic (DEP)
      force and randomized by Brownian motion. The model is applicable for a
      dielectrophoretic force that spatially decays from the electrode array according
      to a reciprocal-law; that is, in the near field of a planar interdigitated array
      or in the far field where other long range forces assist DEP transport, e.g., ac
      electro-osmosis. Capabilities of the model are demonstrated for estimating and
      decomposing data typical of dielectrophoretic bionanoparticle collection
      experiments. An important approximation, for moderately strong DEP forces, is
      that a collection can largely be described by a single exponential profile with a
      square-law dependence on microdevice chamber height. Applications of the model
      demonstrate transformation and representation of time-dependent bionanoparticle
      transport in the frequency domain and prediction of a modulation bandwidth that
      concurs with experimental observations.

PMID- 22157080
TI  - Capturing ultrasmall EMT zeolite from template-free systems.
AB  - Small differences between the lattice energies of different zeolites suggest that
      kinetic factors are of major importance in controlling zeolite nucleation. Thus,
      it is critical to control the nucleation kinetics in order to obtain a desired
      microporous material. Here, we demonstrate how careful investigation of the very
      early stages of zeolite crystallization in colloidal systems can provide access
      to important nanoscale zeolite phases while avoiding the use of expensive organic
      templates. We report the effective synthesis of ultrasmall (6- to 15-nanometer)
      crystals of the large-pore zeolite EMT from template-free colloidal precursors at
      low temperature (30 degrees C) and very high yield.

PMID- 22157079
TI  - A SUMOylation-dependent transcriptional subprogram is required for Myc-driven
      tumorigenesis.
AB  - Myc is an oncogenic transcription factor frequently dysregulated in human cancer.
      To identify pathways supporting the Myc oncogenic program, we used a genome-wide
      RNA interference screen to search for Myc-synthetic lethal genes and uncovered a
      role for the SUMO-activating enzyme (SAE1/2). Loss of SAE1/2 enzymatic activity
      drives synthetic lethality with Myc. Inactivation of SAE2 leads to mitotic
      catastrophe and cell death upon Myc hyperactivation. Mechanistically, SAE2
      inhibition switches a transcriptional subprogram of Myc from activated to
      repressed. A subset of these SUMOylation-dependent Myc switchers (SMS genes) is
      required for mitotic spindle function and to support the Myc oncogenic program.
      SAE2 is required for growth of Myc-dependent tumors in mice, and gene expression
      analyses of Myc-high human breast cancers suggest that low SAE1 and SAE2
      abundance in the tumors correlates with longer metastasis-free survival of the
      patients. Thus, inhibition of SUMOylation may merit investigation as a possible
      therapy for Myc-driven human cancers.

PMID- 22157081
TI  - Stop signals provide cross inhibition in collective decision-making by honeybee
      swarms.
AB  - Honeybee swarms and complex brains show many parallels in how they make
      decisions. In both, separate populations of units (bees or neurons) integrate
      noisy evidence for alternatives, and, when one population exceeds a threshold,
      the alternative it represents is chosen. We show that a key feature of a brain-
      cross inhibition between the evidence-accumulating populations--also exists in a
      swarm as it chooses its nesting site. Nest-site scouts send inhibitory stop
      signals to other scouts producing waggle dances, causing them to cease dancing,
      and each scout targets scouts' reporting sites other than her own. An analytic
      model shows that cross inhibition between populations of scout bees increases the
      reliability of swarm decision-making by solving the problem of deadlock over
      equal sites.

PMID- 22157082
TI  - Synthetic partial waves in ultracold atomic collisions.
AB  - Interactions between particles can be strongly altered by their environment. We
      demonstrate a technique for modifying interactions between ultracold atoms by
      dressing the bare atomic states with light, creating an effective interaction of
      vastly increased range that scatters states of finite relative angular momentum
      at collision energies where only s-wave scattering would normally be expected. We
      collided two optically dressed neutral atomic Bose-Einstein condensates with
      equal, and opposite, momenta and observed that the usual s-wave distribution of
      scattered atoms was altered by the appearance of d- and g-wave contributions.
      This technique is expected to enable quantum simulation of exotic systems,
      including those predicted to support Majorana fermions.

PMID- 22157083
TI  - Cytoplasmic dynein moves through uncoordinated stepping of the AAA+ ring domains.
AB  - Cytoplasmic dynein is a homodimeric AAA+ motor that transports a multitude of
      cargos toward the microtubule minus end. How the two catalytic head domains
      interact and move relative to each other during processive movement is unclear.
      Here, we tracked the relative positions of both heads with nanometer precision
      and directly observed the heads moving independently along the microtubule. The
      heads remained widely separated, and their stepping behavior varied as a function
      of interhead separation. One active head was sufficient for processive movement,
      and an active head could drag an inactive partner head forward. Thus, dynein
      moves processively without interhead coordination, a mechanism fundamentally
      distinct from the hand-over-hand stepping of kinesin and myosin.

PMID- 22157084
TI  - Behavior. How honeybees break a decision-making deadlock.

PMID- 22157085
TI  - Sucrose efflux mediated by SWEET proteins as a key step for phloem transport.
AB  - Plants transport fixed carbon predominantly as sucrose, which is produced in
      mesophyll cells and imported into phloem cells for translocation throughout the
      plant. It is not known how sucrose migrates from sites of synthesis in the
      mesophyll to the phloem, or which cells mediate efflux into the apoplasm as a
      prerequisite for phloem loading by the SUT sucrose-H(+) (proton) cotransporters.
      Using optical sucrose sensors, we identified a subfamily of SWEET sucrose efflux
      transporters. AtSWEET11 and 12 localize to the plasma membrane of the phloem.
      Mutant plants carrying insertions in AtSWEET11 and 12 are defective in phloem
      loading, thus revealing a two-step mechanism of SWEET-mediated export from
      parenchyma cells feeding H(+)-coupled import into the sieve element-companion
      cell complex. We discuss how restriction of intercellular transport to the
      interface of adjacent phloem cells may be an effective mechanism to limit the
      availability of photosynthetic carbon in the leaf apoplasm in order to prevent
      pathogen infections.

PMID- 22157086
TI  - Association between environmental factors and CDX2 expression in gastric cancer
      patients.
AB  - Intestinal differentiation, mediated by CDX2, may occur both in intestinal and in
      diffuse gastric carcinomas. In an attempt to ascertain the environmental
      determinants of the intestinal differentiation pathway, we aimed to compare the
      exposure to environmental factors in gastric cancer cases according to the CDX2
      expression status. We evaluated 270 patients undergoing gastrectomy due to
      gastric adenocarcinoma. Cases were classified according to tumour location within
      the stomach, Lauren's histological type and CDX2 expression. Participants
      completed a comprehensive structured questionnaire on sociodemographic and
      behavioural characteristics and provided a blood sample for assessment of
      Helicobacter pylori infection status. Odds ratios with 95% confidence intervals
      were computed by unconditional logistic regression to compare cancer cases
      according to histological type and CDX2 expression status. Approximately 80% of
      the patients expressed CDX2, regardless of the histological type and location of
      the tumour. No statistically significant or consistent associations between
      sociodemographic or environmental exposures and CDX2 expression status were
      observed, except for a decreased risk of CDX2 expression in those with higher
      coffee consumption for tumours of the intestinal type (>= 1 vs. <1 cup/day: odds
      ratio =0.36, 95% confidence interval: 0.13-0.97). In conclusion, this is the
      first study to use CDX2 expression as a finer marker of intestinal
      differentiation to distinguish aetiologically distinct subgroups of gastric
      cancer, adding new evidence to the previous research on the determinants of
      cancer of Lauren's intestinal and diffuse types.

PMID- 22157087
TI  - Antigenotoxic action of isothiocyanate-containing mustard as determined by two
      cancer biomarkers in a human intervention trial.
AB  - Chemopreventive constituents in food plants, such as brassica-derived
      isothiocyanates (ITC), have been shown to be quite effective in the prevention of
      genotoxic DNA damage in cell culture models and carcinogenesis in laboratory
      animals. We have conducted a controlled intervention study with 14 participants
      (10 female, four male) using DNA damage and micronucleus formation as
      intermediate endpoints to assess the chemopreventive nature of mustard. For this
      trial, human volunteers were fed 20 g (25 mg total ITC) of mustard preparation,
      daily, for 4 days. Heparinized blood was collected by venipuncture and processed
      for the comet assay or the micronucleus test. A 3-day intervention with mustard
      led to a significant reduction in DNA damage and micronucleus formation induced
      by hydrogen peroxide or benzo(a)pyrene diolepoxide. Clinical liver parameters
      were unchanged by the intervention; however, cholesterol levels were
      significantly reduced. The results of this study indicate that consumption of low
      amounts of ITC-containing mustard quickly and effectively modulates
      cytoprotective factors in peripheral blood mononuclear cells and/or blood. The
      fact that these observations were confirmed by two cytogenetic biomarkers for
      cancer risk implies that even short-term intake of ITC-containing vegetables
      might indeed be associated with reduced cancer risk.

PMID- 22157089
TI  - The patient-centered medical home: the ideal "location" for cardiovascular
      disease prevention?

PMID- 22157090
TI  - News about old histones: a role for histone age in controlling the epigenome.

PMID- 22157091
TI  - Determinants of Wnt/beta-catenin pathway dependency in colorectal cancer.

PMID- 22157093
TI  - Modulation of WNT signaling activity is key to the formation of the embryonic
      head.
AB  - The formation of the embryonic head begins with the assembly of the progenitor
      tissues of the brain, the head and face primordia and the foregut that are
      derived from the primary germ layers during gastrulation. Specification of the
      anterior-posterior polarity of major body parts and the morphogenesis of the head
      and brain specifically is driven by inductive signals including those mediated by
      BMP, Nodal, FGF and WNT. A critical role of beta-catenin dependent WNT signalling
      activity for head morphogenesis has been revealed through the analysis of the
      phenotypic impact of loss of function mutation of an antagonist: DKK1, a
      transcriptional repressor: GSC; and the outcome of interaction of Dkk1 with genes
      coding three components of the canonical signalling pathway: the ligand WNT3, the
      co-receptor LRP6 and the transcriptional co-factor, beta-catenin. The findings
      highlight the requirement of a stringent control of the timing, domain and level
      of canonical WNT signalling activity for the formation of the embryonic head.

PMID- 22157092
TI  - APOBEC3 proteins and genomic stability: the high cost of a good defense.
AB  - The human APOBEC3 family of cytidine deaminases constitutes a cellular intrinsic
      defense mechanism that is effective against a range of viruses and retro
      elements. While it is well established that these enzymes are powerful mutators
      of viral DNA, the possibility that their activity could threaten the integrity of
      the host genome has only recently begun to be investigated. Here, we discuss the
      implications of new evidence suggesting that APOBEC3 proteins can mediate the
      deamination of cellular DNA. The maintenance of genomic integrity in the face of
      this potential off-target activity must require high fidelity DNA repair and
      strict regulation of APOBEC3 gene expression and enzyme activity. Conversely, the
      ability of specific members of the APOBEC3 family to activate DNA damage
      signaling pathways might also reflect another way that these proteins contribute
      to the host immune response.

PMID- 22157094
TI  - Fates and roles of post-mitotic midbodies beyond cytokinesis.

PMID- 22157095
TI  - DAPk and pyruvate kinase: unlikely partners in cancer metabolic regulation.

PMID- 22157097
TI  - Success criteria in implant dentistry: a systematic review.
AB  - The purpose of this study was to examine the most frequently used criteria to
      define treatment success in implant dentistry. An electronic MEDLINE/PubMED
      search was conducted to identify randomized controlled trials and prospective
      studies reporting on outcomes of implant dentistry. Only studies conducted with
      roughened surface implants and at least five-year follow-up were included. Data
      were analyzed for success at the implant level, peri-implant soft tissue,
      prosthetics, and patient satisfaction. Most frequently reported criteria for
      success at the implant level were mobility, pain, radiolucency, and peri-implant
      bone loss (> 1.5 mm), and for success at the peri-implant soft-tissue level,
      suppuration, and bleeding. The criteria for success at the prosthetic level were
      the occurrence of technical complications/prosthetic maintenance, adequate
      function, and esthetics during the five-year period. The criteria at patient
      satisfaction level were discomfort and paresthesia, satisfaction with appearance,
      and ability to chew/taste. Success in implant dentistry should ideally evaluate a
      long-term primary outcome of an implant-prosthetic complex as a whole.

PMID- 22157096
TI  - A role for sister telomere cohesion in telomere elongation by telomerase.
AB  - Telomere length homeostasis is achieved by a balance of telomere shortening
      caused by DNA replication and nucleolytic attack and telomere lengthening by
      telomerase. The importance of telomere length maintenance to human health is best
      illustrated by dyskeratosis congenita (DC) a disease of telomere shortening
      caused by mutations in telomerase subunits. DC patients suffer stem cell
      depletion and die of bone marrow stem cell failure. Recently a new class of
      particularly severe DC patients was found to harbor mutations in the shelterin
      subunit TIN2. The DC-TIN2 mutations were clustered in small domain of unknown
      function. In a recently published study we showed that the DC mutation cluster in
      TIN2 harbored a binding site for heterochromatin protein 1 (HP1) and further,
      that HP1 binding to TIN2 was required for sister telomere cohesion in S phase and
      for telomere length maintenance by telomerase. We briefly review and discuss the
      implications of our findings in this Extra View, and present some new data that
      may shed light on how sister telomere cohesion could influence telomere
      elongation by telomerase.

PMID- 22157098
TI  - Relationship between periodontal status and levels of glycated hemoglobin.
AB  - The objective of this study was to assess whether there is a bi-directional
      relationship between periodontal status and diabetes. Study 1 included 5,856
      people without periodontal pockets of >= 4 mm at baseline. Relative risk was
      estimated for the 5-year incidence of periodontal pockets of >= 4 mm (CPI scores
      3 and 4, with the CPI probe), in individuals with glycated hemoglobin (HbA1c)
      levels of >= 6.5% at baseline. Study 2 included 6,125 people with HbA1c < 6.5% at
      baseline. The relative risk was assessed for elevation of HbA1c levels in 5
      years, with baseline periodontal status, assessed by CPI. Relative risk of
      developing a periodontal pocket was 1.17 (p = 0.038) times greater in those with
      HbA1c of >= 6.5% at baseline, adjusted for body mass index (BMI), smoking status,
      sex, and age. Relative risks for having HbA1c >= 6.5% at 5-year follow-up in
      groups with periodontal pockets of 4 to 5 mm and >= 6 mm at baseline were 2.47 (p
      = 0.122) and 3.45 (p = 0.037), respectively, adjusted for BMI, alcohol
      consumption, smoking status, sex, and age. The risk of developing periodontal
      disease was associated with levels of HbA1c, and the risk of elevations of HbA1c
      was associated with developing periodontal pockets of more than 4 mm.

PMID- 22157099
TI  - Tracing toothache intensity in the brain.
AB  - Identification of brain regions that differentially respond to pain intensity may
      improve our understanding of trigeminally mediated nociception. This report
      analyzed cortical responses to painless and painful electrical stimulation of a
      right human maxillary canine tooth. Functional magnetic resonance images were
      obtained during the application of five graded stimulus strengths, from below,
      at, and above the individually determined pain thresholds. Study participants
      reported each stimulus on a visual rating scale with respect to evoked sensation.
      Based on hemodynamic responses of all pooled stimuli, a cerebral network was
      identified that largely corresponds to the known lateral and medial nociceptive
      system. Further analysis of the five graded stimulus strengths revealed positive
      linear correlations for the anterior insula bilaterally, the contralateral (left)
      anterior mid-cingulate, as well as contralateral (left) pregenual cingulate
      cortices. Cerebral toothache intensity coding on a group level can thus be
      attributed to specific subregions within the cortical pain network.

PMID- 22157100
TI  - Randomized trial on the effectiveness of dexamethasone in TMJ arthrocentesis.
AB  - The aim of this study was to compare the effectiveness of dexamethasone
      administration following arthrocentesis of the temporomandibular joint (TMJ) with
      a placebo (saline). Twenty-eight participants with TMJ arthralgia were randomly
      assigned to two groups of a parallel double-blind RCT. In both groups, an
      arthrocentesis procedure was carried out. In one group, the procedure was
      followed by the administration of a single-dose intra-articular dexamethasone. In
      the other group, saline was administered as a control. Follow-up visits were
      scheduled after 1, 3, and 24 weeks. During each visit, TMJ pain (on a 100-mm VAS)
      and jaw stiffness (mouth opening in mm) were scored. In the statistical analysis,
      generalized estimating equation (GEE) models showed no differences between the
      two study groups, although pain and jaw stiffness were both reduced over 24
      weeks. In conclusion, intra-articular dexamethasone following arthrocentesis did
      not improve the procedure's effect in patients presenting with TMJ arthralgia
      (ClinicalTrials.gov number CT01275014).

PMID- 22157101
TI  - "The family factor" knowledge needed in oncology research.

PMID- 22157102
TI  - To remain "new" to what is familiar.

PMID- 22157103
TI  - Effects of polychlorinated biphenyls in CD-1 mice: reproductive toxicity and
      intergenerational transmission.
AB  - Several studies indicate that in utero and perinatal exposure to polychlorinated
      biphenyls (PCBs) induces adverse reproductive effects, but it remains unclear
      whether such effects may be transmitted to subsequent generations. We therefore
      investigated the association between maternal exposure to PCBs and reproductive
      health in male and female offspring over three generations. Mouse dams were fed
      0, 1, 10, and 100 MUg/kg/day of a PCB mixture (101 + 118) during pregnancy and
      lactation. PCB levels were measured in the tissues of both dams and offspring.
      PCB concentrations at all doses investigated were greater in the offspring than
      in the dams (p <= 0.0001) confirming that the progeny were exposed as a result of
      maternal exposure. In F1 offspring, exposure to PCBs resulted in reductions in
      (1) testis weight (p <= 0.05) and seminiferous tubule diameter (p <= 0.05), (2)
      sperm viability (p <= 0.0001) and developmental capacity (p <= 0.05), (3) ovary
      weight (p <= 0.05), (4) oocyte developmental capacity (p <= 0.05), and (5)
      increased follicular atresia (p <= 0.0001). In females, adverse effects were
      observed only in the F1 animals. In contrast, male offspring exhibited reduced
      sperm viability and altered seminiferous tubule distribution up to the third
      generation, showing intergenerational transmission. In summary, our data indicate
      that exposure to PCBs at the time of gonadal sex determination perturbed,
      significantly, the reproductive physiology of male and female offspring in
      adulthood. Furthermore, male reproductive deficiencies may be observed in at
      least two further generations. These findings have significant implications for
      reproductive health and fertility of animals and humans.

PMID- 22157104
TI  - Mechanism of exacerbative effect of progesterone on drug-induced liver injury.
AB  - Drug-induced liver injury (DILI) is a major safety concern in drug development
      and clinical drug therapy. However, the underlying mechanism of DILI is little
      known. It is generally believed that women exhibit worse outcomes from DILI than
      men. Recently, we found that pretreatment of mice with estradiol attenuated
      halothane (HAL)-induced liver injury, whereas pretreatment with progesterone
      exacerbated it in female mice. To investigate the mechanism of sex difference of
      DILI, we focused on progesterone in this study. We found the exacerbating effect
      of progesterone in thioacetamide (TA), alpha-naphthylisothiocyanate, and
      dicloxacillin-induced liver injury only in female mice. Higher number of
      myeloperoxidase-positive mononuclear cells infiltrated into the liver and
      increased levels of Chemokine (C-X-C motif) ligand 1 and 2 (CXCL1 and CXCL2) and
      intercellular adhesion molecule-1 in the liver were observed. Interestingly,
      CXCL1 was slightly increased by progesterone pretreatment alone. Progesterone
      pretreatment increased the extracellular signal-regulated kinase (ERK)
      phosphorylation in HAL-induced liver injury. Pretreatment with U0126 (ERK
      inhibitor) significantly suppressed the exacerbating effect of progesterone and
      the expression of inflammatory mediators. In addition, pretreatment with
      gadolinium chloride (GdCl(3): inhibitor of Kupffer cells) significantly
      suppressed the exacerbating effect of progesterone pretreatment and the
      expression of inflammatory mediators. Moreover, posttreatment of RU486
      (progesterone receptor antagonist) 1 h after the HAL or TA administration
      ameliorated the HAL- or TA-induced liver injury, respectively, in female mice. In
      conclusion, progesterone exacerbated the immune-mediated hepatotoxic responses in
      DILI via Kupffer cells and ERK pathway. The inhibition of progesterone receptor
      and decrease of the immune response may have important therapeutic implications
      in DILI.

PMID- 22157105
TI  - Telestroke increases use of acute stroke therapy.
AB  - PURPOSE OF REVIEW: This review provides a comprehensive overview of the
      management of acute stroke within the framework of telestroke services. RECENT
      FINDINGS: The remote neurological examination using high quality
      videoconferencing coupled with remote review of neuroimaging has gained
      acceptance and proved its reliability in various publications. Telestroke
      networks confirmed the safety and efficiency of telethrombolysis, with an
      increase in the rate of thrombolysis in recent years. The analysis of a
      telestroke network in Europe showed improved outcomes in a cohort of ischemic
      stroke patients. SUMMARY: At the beginning of the millennium, telestroke networks
      started to develop. Ten years later, there is a collection of about 40 various
      networks in North America and Europe performing teleconsultations on a regular
      basis. Telestroke is not a new therapeutic modality, but rather a set of tools to
      enable more efficient delivery of acute stroke care and to improve the quality of
      stroke care in neurologically underserved areas. Depending on the level of
      available regional resources, telestroke networks can support affiliated
      hospitals by implementing measures that improve the quality of stroke management
      such as regional campaigns, stroke units and stroke teams, medical education and
      programs encouraging the usage of guidelines.

PMID- 22157106
TI  - Traditional risk factor management for stroke:  a never-ending challenge for
      health behaviors of diet and physical activity.
AB  - PURPOSE OF REVIEW: Recently, many guidelines have given new evidence on the risk
      factors for stroke. In this review, I refer to the most important guidelines for
      primary prevention of stroke and hypertension, especially focused on diet and
      physical activity. RECENT FINDINGS: The health behavior recommendations in recent
      guidelines for the primary prevention of stroke are virtually identical, and the
      same recommendations appear in the recent guidelines for the management of
      hypertension, especially with respect to diet and physical activity. The
      recommended health behaviors consist of weight reduction, reduction of salt
      intake, increase in fruit and vegetable intake, decrease in saturated and total
      fat intake (increase in fish intake), physical activity, and moderation of
      alcohol consumption. Fruits and vegetables have high levels of potassium,
      antioxidants, phytochemicals, and dietary fiber, and thus are also considered
      preventive of cardiovascular disease and its risk factors. It was found that
      individuals with many of these health behaviors have been shown to have a lowered
      risk of stroke. SUMMARY: The health behaviors, especially those related to diet
      and physical activity, appearing in recent guidelines for the management of
      hypertension are also important for the primary prevention of stroke, and appear
      in recent stroke guidelines.

PMID- 22157107
TI  - The brain as a flexible task machine:  implications for visual rehabilitation
      using noninvasive vs. invasive approaches.
AB  - PURPOSE OF REVIEW: The exciting view of our brain as highly flexible task-based
      and not sensory-based raises the chances for visual rehabilitation, long
      considered unachievable, given adequate training in teaching the brain how to
      see. Recent advances in rehabilitation approaches, both noninvasive, like sensory
      substitution devices (SSDs) which present visual information using sound or
      touch, and invasive, like visual prosthesis, may potentially be used to achieve
      this goal, each alone, and most preferably together. RECENT FINDINGS: Visual
      impairments and said solutions are being used as a model for answering
      fundamental questions ranging from basic cognitive neuroscience, showing that
      several key visual brain areas are actually highly flexible, modality-independent
      and, as was recently shown, even visual experience-independent task machines, to
      technological and behavioral developments, allowing blind persons to 'see' using
      SSDs and other approaches. SUMMARY: SSDs can be potentially used as a research
      tool for assessing the brain's functional organization; as an aid for the blind
      in daily visual tasks; to visually train the brain prior to invasive procedures,
      by taking advantage of the 'visual' cortex's flexibility and task specialization
      even in the absence of vision; and to augment postsurgery functional vision using
      a unique SSD-prostheses hybrid. Taken together the reviewed results suggest a
      brighter future for visual neuro-rehabilitation.

PMID- 22157108
TI  - Retinal and cochlear toxicity of drugs:  new insights into mechanisms and
      detection.
AB  - PURPOSE OF REVIEW: Various medications can modify the physiology of retinal and
      cochlear neurons and lead to major, sometime permanent, sensory loss. A better
      knowledge of pathogenic mechanisms and the establishment of relevant monitoring
      protocols are necessary to prevent permanent sensory impairment. In this article,
      we review main systemic medications associated with direct neuronal toxicity on
      the retina and cochlea, their putative pathogenic mechanisms, when identified, as
      well as current recommendations, when available, for monitoring protocols. RECENT
      FINDINGS: Pathogenic mechanisms and cellular target of retinotoxic drugs are
      often not well characterized but a better knowledge of the course of visual
      defect has recently helped in defining more relevant monitoring protocols
      especially for antimalarials and vigabatrin. Mechanisms of ototoxicity have
      recently been better defined, from inner ear entry with the use of fluorescent
      tracers to evidence for the role of oxidative stress and program cell death
      pathways. SUMMARY: Experimental and clinical studies have elucidated some of the
      pathogenic mechanisms, courses and risk factors of retinal toxicity and
      ototoxicity, which have led to establishment of relevant monitoring protocols.
      Further studies are, however, warranted to better understand cellular pathways
      leading to degeneration. These would help to build more efficient preventive
      intervention and may also contribute to understanding of other degenerative
      processes such as genetic disorders.

PMID- 22157109
TI  - Advances in auditory prostheses.
AB  - PURPOSE OF REVIEW: Auditory prostheses use electric currents on multiple
      electrodes to stimulate auditory neurons and recreate auditory sensations in deaf
      people. Cochlear implants have restored hearing in more than 200  000 deaf adults
      and children to a level that allows most to understand speech. Here we review the
      reasons underlying these results and describe new directions in restoring hearing
      to additional patient populations and the design of new devices. RECENT FINDINGS:
      From their early development about 50 years ago, cochlear implants have been well
      received and beneficial to people who had lost their hearing. Although those
      first implants did not allow high levels of speech understanding, they provided
      auditory information that worked synergistically with lip reading to improve
      communication. Present day cochlear implants provide excellent speech
      understanding in children and in postlingually deafened adults. Research is
      focused on improved signal processing and new electrode designs. Electric
      stimulation of the auditory brainstem can also produce excellent hearing in some
      children and adults. SUMMARY: Auditory prostheses, both at the level of the
      sensory nerve and at the brainstem, can restore patterns of neural activation
      that are sufficient for high levels of speech understanding. These prostheses are
      not only clinically successful but also important tools for understanding sensory
      processing in the brain.

PMID- 22157110
TI  - Cochlear gene therapy.
AB  - PURPOSE OF REVIEW: This review highlights recent advances in cochlear gene
      therapy over the past several years. Cochlear gene therapy has undergone
      tremendous advances over the past decade. Beginning with some groundbreaking work
      in 2005 documenting hair cell regeneration using virally mediated delivery of the
      mouse atonal 1 gene, gene therapy is now being explored as a possible treatment
      for a variety of causes of hearing loss. RECENT FINDINGS: Recent advances in
      cochlear gene therapy include improved methods of gene delivery with a better
      delineation of viral vectors that are suitable for this purpose, additional
      improvements in hair cell regeneration, and directed research toward autoimmune
      hearing loss, ototoxicity, spiral ganglion survival, and genetic forms of hearing
      loss. SUMMARY: If successful, cochlear gene therapy will dramatically alter our
      ability to treat a variety of forms of acquired and genetic hearing loss.

PMID- 22157111
TI  - Short- and long-latency somatosensory neuronal responses reveal selective brain
      injury and effect of hypothermia in global hypoxic ischemia.
AB  - Evoked potentials recorded from the somatosensory cortex have been shown to be an
      electrophysiological marker of brain injury in global hypoxic ischemia (HI). The
      evoked responses in somatosensory neurons carry information pertaining to signal
      from the ascending pathway in both the subcortical and cortical areas. In this
      study, origins of the subcortical and cortical signals are explored by
      decomposing the evoked neuronal activities into short- and long-latency responses
      (SLR and LLR), respectively. We evaluated the effect of therapeutic hypothermia
      on SLR and LLR during early recovery from cardiac arrest (CA)-induced HI in a
      rodent model. Twelve rats were subjected to CA, after which half of them were
      treated with hypothermia (32-34 degrees C) and the rest were kept at normal
      temperature (36-37 degrees C). Evoked neuronal activities from the primary
      somatosensory cortex, including multiunit activity (MUA) and local field
      potential (LFP), were continuously recorded during injury and early recovery.
      Results showed that upon initiation of injury, LLR disappeared first, followed by
      the disappearance of SLR, and after a period of isoelectric silence SLR
      reappeared prior to LLR. This suggests that cortical activity, which primarily
      underlies the LLR, may be more vulnerable to ischemic injury than SLR, which
      relates to subcortical activity. Hypothermia potentiated the SLR but suppressed
      the LLR by delaying its recovery after CA (hypothermia: 38.83 +/- 5.86 min,
      normothermia: 23.33 +/- 1.15 min; P < 0.05) and attenuating its amplitude,
      suggesting that hypothermia may selectively downregulate cortical activity as an
      approach to preserve the cerebral cortex. In summary, our study reveals the
      vulnerability of the somatosensory neural structures to global HI and the
      differential effects of hypothermia on these structures.

PMID- 22157112
TI  - Relationships between spike-free local field potentials and spike timing in human
      temporal cortex.
AB  - Intracortical recordings comprise both fast events, action potentials (APs), and
      slower events, known as local field potentials (LFPs). Although it is believed
      that LFPs mostly reflect local synaptic activity, it is unclear which of their
      signal components are most closely related to synaptic potentials and would
      therefore be causally related to the occurrence of individual APs. This issue is
      complicated by the significant contribution from AP waveforms, especially at
      higher LFP frequencies. In recordings of single-cell activity and LFPs from the
      human temporal cortex, we computed quantitative, nonlinear, causal dynamic models
      for the prediction of AP timing from LFPs, at millisecond resolution, before and
      after removing AP contributions to the LFP. In many cases, the timing of a
      significant number of single APs could be predicted from spike-free LFPs at
      different frequencies. Not surprisingly, model performance was superior when
      spikes were not removed. Cells whose activity was predicted by the spike-free LFP
      models generally fell into one of two groups: in the first group, neuronal spike
      activity was associated with specific phases of low LFP frequencies, lower spike
      activity at high LFP frequencies, and a stronger linear component in the spike
      LFP model; in the second group, neuronal spike activity was associated with
      larger amplitude of high LFP frequencies, less frequent phase locking, and a
      stronger nonlinear model component. Spike timing in the first group was better
      predicted by the sign and level of the LFP preceding the spike, whereas spike
      timing in the second group was better predicted by LFP power during a certain
      time window before the spike.

PMID- 22157113
TI  - Parameter extraction and classification of three cortical neuron types reveals
      two distinct adaptation mechanisms.
AB  - Cortical information processing originates from the exchange of action potentials
      between many cell types. To capture the essence of these interactions, it is of
      critical importance to build mathematical models that reflect the characteristic
      features of spike generation in individual neurons. We propose a framework to
      automatically extract such features from current-clamp experiments, in particular
      the passive properties of a neuron (i.e., membrane time constant, reversal
      potential, and capacitance), the spike-triggered adaptation currents, as well as
      the dynamics of the action potential threshold. The stochastic model that results
      from our maximum likelihood approach accurately predicts the spike times, the
      subthreshold voltage, the firing patterns, and the type of frequency-current
      curve. Extracting the model parameters for three cortical cell types revealed
      that cell types show highly significant differences in the time course of the
      spike-triggered currents and moving threshold, that is, in their adaptation and
      refractory properties but not in their passive properties. In particular,
      GABAergic fast-spiking neurons mediate weak adaptation through spike-triggered
      currents only, whereas regular spiking excitatory neurons mediate adaptation with
      both moving threshold and spike-triggered currents. GABAergic nonfast-spiking
      neurons combine the two distinct adaptation mechanisms with reduced strength.
      Differences between cell types are large enough to enable automatic
      classification of neurons into three different classes. Parameter extraction is
      performed for individual neurons so that we find not only the mean parameter
      values for each neuron type but also the spread of parameters within a group of
      neurons, which will be useful for future large-scale computer simulations.

PMID- 22157114
TI  - Causes of social reward differences encoded in human brain.
AB  - Rewards may be due to skill, effort, and luck, and the social perception of
      inequality in rewards among individuals may depend on what produced the
      inequality. Rewards due to skill produce a conflict: higher outcomes of others in
      this case are considered deserved, and this counters incentives to reduce
      inequality. However, they also signal superior skill and for this reason induce
      strong negative affect in those who perform less, which increases the incentive
      to reduce the inequality. The neurobiological mechanisms underlying evaluation of
      rewards due to skill, effort, and luck are still unknown. We scanned brain
      activity of subjects as they perceived monetary rewards caused by skill, effort,
      or luck. Subjects could subtract from others. Subtraction was larger, everything
      else being equal, in luck but increased more as the difference in outcomes grew
      in skill. Similarly, reward-related activation in medial orbitofrontal cortex was
      more sensitive to the difference in relative outcomes in skill trials.
      Orbitofrontal activation reflecting comparative reward advantage predicted by how
      much subjects reduced unfavorable reward inequality later on in the trial. Thus
      medial orbitofrontal cortex activity reflects the causes of reward and predicts
      actions that reduce inequality.

PMID- 22157115
TI  - Decoding 3D reach and grasp from hybrid signals in motor and premotor cortices:
      spikes, multiunit activity, and local field potentials.
AB  - Neural activity in motor cortex during reach and grasp movements shows
      modulations in a broad range of signals from single-neuron spiking activity (SA)
      to various frequency bands in broadband local field potentials (LFPs). In
      particular, spatiotemporal patterns in multiband LFPs are thought to reflect
      dendritic integration of local and interareal synaptic inputs, attentional and
      preparatory processes, and multiunit activity (MUA) related to movement
      representation in the local motor area. Nevertheless, the relationship between
      multiband LFPs and SA, and their relationship to movement parameters and their
      relative value as brain-computer interface (BCI) control signals, remain poorly
      understood. Also, although this broad range of signals may provide complementary
      information channels in primary (MI) and ventral premotor (PMv) areas, areal
      differences in information have not been systematically examined. Here, for the
      first time, the amount of information in SA and multiband LFPs was compared for
      MI and PMv by recording from dual 96-multielectrode arrays while monkeys made
      naturalistic reach and grasp actions. Information was assessed as decoding
      accuracy for 3D arm end point and grip aperture kinematics based on SA or LFPs in
      MI and PMv, or combinations of signal types across areas. In contrast with
      previous studies with <=16 simultaneous electrodes, here ensembles of >16 units
      (on average) carried more information than multiband, multichannel LFPs.
      Furthermore, reach and grasp information added by various LFP frequency bands was
      not independent from that in SA ensembles but rather typically less than and
      primarily contained within the latter. Notably, MI and PMv did not show a
      particular bias toward reach or grasp for this task or for a broad range of
      signal types. For BCIs, our results indicate that neuronal ensemble spiking is
      the preferred signal for decoding, while LFPs and combined signals from PMv and
      MI can add robustness to BCI control.

PMID- 22157116
TI  - Auditory experience refines cortico-basal ganglia inputs to motor cortex via
      remapping of single axons during vocal learning in zebra finches.
AB  - Experience-dependent changes in neural connectivity underlie developmental
      learning and result in life-long changes in behavior. In songbirds axons from the
      cortical region LMAN(core) (core region of lateral magnocellular nucleus of
      anterior nidopallium) convey the output of a basal ganglia circuit necessary for
      song learning to vocal motor cortex [robust nucleus of the arcopallium (RA)].
      This axonal projection undergoes remodeling during the sensitive period for
      learning to achieve topographic organization. To examine how auditory experience
      instructs the development of connectivity in this pathway, we compared the
      morphology of individual LMAN(core)->RA axon arbors in normal juvenile songbirds
      to those raised in white noise. The spatial extent of axon arbors decreased
      during the first week of vocal learning, even in the absence of normal auditory
      experience. During the second week of vocal learning axon arbors of normal birds
      showed a loss of branches and varicosities; in contrast, experience-deprived
      birds showed no reduction in branches or varicosities and maintained some arbors
      in the wrong topographic location. Thus both experience-independent and
      experience-dependent processes are necessary to establish topographic
      organization in juvenile birds, which may allow birds to modify their vocal
      output in a directed manner and match their vocalizations to a tutor song. Many
      LMAN(core) axons of juvenile birds, but not adults, extended branches into dorsal
      arcopallium (Ad), a region adjacent to RA that is part of a parallel basal
      ganglia pathway also necessary for vocal learning. This transient projection
      provides a point of integration between the two basal ganglia pathways,
      suggesting that these branches convey corollary discharge signals as birds are
      actively engaged in learning.

PMID- 22157117
TI  - What is the role of the medial olivocochlear system in speech-in-noise
      processing?
AB  - The medial olivocochlear (MOC) bundle reduces the gain of the cochlear amplifier
      through reflexive activation by sound. Physiological results indicate that MOC
      induced reduction in cochlear gain can enhance the response to signals when
      presented in masking noise. Some previous studies suggest that this "antimasking"
      effect of the MOC system plays a role in speech-in-noise perception. The present
      study set out to reinvestigate this hypothesis by correlating measures of MOC
      activity and speech-in-noise processing across a group of normal-hearing
      participants. MOC activity was measured using contralateral suppression of
      otoacoustic emissions (OAEs), and speech-in-noise processing was measured by
      measuring the effect of noise masking on performance in a consonant-vowel (CV)
      discrimination task and on auditory brain stem responses evoked by a CV syllable.
      Whereas there was a significant correlation between OAE suppression and both
      measures of speech-in-noise processing, the direction of this correlation was
      opposite to that predicted by the antimasking hypothesis, in that individuals
      with stronger OAE suppression tended to show greater noise-masking effects on CV
      processing. The current results indicate that reflexive MOC activation is not
      always beneficial to speech-in-noise processing. We propose an alternative to the
      antimasking hypothesis, whereby the MOC system benefits speech-in-noise
      processing through dynamic (e.g., attention- and experience-dependent), rather
      than reflexive, control of cochlear gain.

PMID- 22157118
TI  - Preparing for the unpredictable: adaptive feedback enhances the response to
      unexpected communication signals.
AB  - To interact with the environment efficiently, the nervous system must generate
      expectations about redundant sensory signals and detect unexpected ones. Neural
      circuits can, for example, compare a prediction of the sensory signal that was
      generated by the nervous system with the incoming sensory input, to generate a
      response selective to novel stimuli. In the first-order electrosensory neurons of
      a gymnotiform electric fish, a negative image of low-frequency redundant
      communication signals is subtracted from the neural response via feedback,
      allowing unpredictable signals to be extracted. Here we show that the cancelling
      feedback not only suppresses the predictable signal but also actively enhances
      the response to the unpredictable communication signal. A transient mismatch
      between the predictive feedback and incoming sensory input causes both to be
      positive: the soma is suddenly depolarized by the unpredictable input, whereas
      the neuron's apical dendrites remain depolarized by the lagging cancelling
      feedback. The apical dendrites allow the backpropagation of somatic spikes. We
      show that backpropagation is enhanced when the dendrites are depolarized, causing
      the unpredictable excitatory input to evoke spike bursts. As a consequence, the
      feedback driven by a predictable low-frequency signal not only suppresses the
      response to a redundant stimulus but also induces a bursting response triggered
      by unpredictable communication signals.

PMID- 22157120
TI  - Beside the point: motor adaptation without feedback-based error correction in
      task-irrelevant conditions.
AB  - Adaptation of movement may be driven by the difference between planned and actual
      motor performance, or the difference between expected and actual sensory
      consequences of movement. To identify how the nervous system differentially uses
      these signals, we asked: does motor adaptation occur when movement errors are
      irrelevant to the task goal? Participants reached on a digitizing tablet from a
      fixed start location to one of three targets: a point, an arc, or a ray. For the
      arc, reaches could be in any direction, but to a specific extent. For the ray,
      reaches could be to any distance, but in a targeted direction. After baseline
      reaching to the point, the direction or extent of continuous visual feedback was
      perturbed during training with either a cursor rotation or gain, respectively,
      while reaching to either the ray (goal = direction) or the arc (goal = extent).
      The perturbation, therefore, was either relevant or irrelevant to the task goal,
      depending on target type. During interspersed catch trials, the perturbation was
      removed and the target switched back to the point, identical to baseline.
      Although the goal of baseline and catch trials was the same, significant
      aftereffects in catch trials indicated behavioral adaptation in response to the
      perturbation. Adaptation occurred regardless of whether the perturbation was
      relevant to the task, and it was independent of feedback control. The presence of
      adaptation orthogonal to task demands supports the hypothesis that the nervous
      system can rely on sensory prediction to drive motor learning that can generalize
      across tasks.

PMID- 22157121
TI  - Foot anatomy specialization for postural sensation and control.
AB  - Anthropological and biomechanical research suggests that the human foot evolved a
      unique design for propulsion and support. In theory, the arch and toes must play
      an important role, however, many postural studies tend to focus on the simple
      hinge action of the ankle joint. To investigate further the role of foot anatomy
      and sensorimotor control of posture, we quantified the deformation of the foot
      arch and studied the effects of local perturbations applied to the toes (TOE) or
      1st/2nd metatarsals (MT) while standing. In sitting position, loading and lifting
      a 10-kg weight on the knee respectively lowered and raised the foot arch between
      1 and 1.5 mm. Less than 50% of this change could be accounted for by plantar
      surface skin compression. During quiet standing, the foot arch probe and shin
      sway revealed a significant correlation, which shows that as the tibia tilts
      forward, the foot arch flattens and vice versa. During TOE and MT perturbations
      (a 2- to 6-mm upward shift of an appropriate part of the foot at 2.5 mm/s),
      electromyogram (EMG) measures of the tibialis anterior and gastrocnemius revealed
      notable changes, and the root-mean-square (RMS) variability of shin sway
      increased significantly, these increments being greater in the MT condition. The
      slow return of RMS to baseline level (>30 s) suggested that a very small
      perturbation changes the surface reference frame, which then takes time to
      reestablish. These findings show that rather than serving as a rigid base of
      support, the foot is compliant, in an active state, and sensitive to minute
      deformations. In conclusion, the architecture and physiology of the foot appear
      to contribute to the task of bipedal postural control with great sensitivity.

PMID- 22157119
TI  - Spike-field activity in parietal area LIP during coordinated reach and saccade
      movements.
AB  - The posterior parietal cortex is situated between visual and motor areas and
      supports coordinated visually guided behavior. Area LIP in the intraparietal
      sulcus contains representations of visual space and has been extensively studied
      in the context of saccades. However, area LIP has not been studied during
      coordinated movements, so it is not known whether saccadic representations in
      area LIP are influenced by coordinated behavior. Here, we studied spiking and
      local field potential (LFP) activity in area LIP while subjects performed
      coordinated reaches and saccades or saccades alone to remembered target locations
      to test whether activity in area LIP is influenced by the presence of a
      coordinated reach. We find that coordination significantly changes the activity
      of individual neurons in area LIP, increasing or decreasing the firing rate when
      a reach is made with a saccade compared with when a saccade is made alone.
      Analyzing spike-field coherence demonstrates that area LIP neurons whose firing
      rate is suppressed during the coordinated task have activity temporally
      correlated with nearby LFP activity, which reflects the synaptic activity of
      populations of neurons. Area LIP neurons whose firing rate increases during the
      coordinated task do not show significant spike-field coherence. Furthermore, LFP
      power in area LIP is suppressed and does not increase when a coordinated reach is
      made with a saccade. These results demonstrate that area LIP neurons display
      different responses to coordinated reach and saccade movements, and that
      different spike rate responses are associated with different patterns of
      correlated activity. The population of neurons whose firing rate is suppressed is
      coherently active with local populations of LIP neurons. Overall, these results
      suggest that area LIP plays a role in coordinating visually guided actions
      through suppression of coherent patterns of saccade-related activity.

PMID- 22157122
TI  - Enhanced intrinsic excitability and EPSP-spike coupling accompany enriched
      environment-induced facilitation of LTP in hippocampal CA1 pyramidal neurons.
AB  - Environmental enrichment (EE) is a well-established paradigm for studying
      naturally occurring changes in synaptic efficacy in the hippocampus that underlie
      experience-induced modulation of learning and memory in rodents. Earlier research
      on the effects of EE on hippocampal plasticity focused on long-term potentiation
      (LTP). Whereas many of these studies investigated changes in synaptic weight,
      little is known about potential contributions of neuronal excitability to EE
      induced plasticity. Here, using whole-cell recordings in hippocampal slices, we
      address this gap by analyzing the impact of EE on both synaptic plasticity and
      intrinsic excitability of hippocampal CA1 pyramidal neurons. Consistent with
      earlier reports, EE increased contextual fear memory and dendritic spine density
      on CA1 cells. Furthermore, EE facilitated LTP at Schaffer collateral inputs to
      CA1 pyramidal neurons. Analysis of the underlying causes for enhanced LTP shows
      EE to increase the frequency but not amplitude of miniature excitatory
      postsynaptic currents. However, presynaptic release probability, assayed using
      paired-pulse ratios and use-dependent block of N-methyl-d-aspartate receptor
      currents, was not affected. Furthermore, CA1 neurons fired more action potentials
      (APs) in response to somatic depolarization, as well as during the induction of
      LTP. EE also reduced spiking threshold and after-hyperpolarization amplitude.
      Strikingly, this EE-induced increase in excitability caused the same-sized
      excitatory postsynaptic potential to fire more APs. Together, these findings
      suggest that EE may enhance the capacity for plasticity in CA1 neurons, not only
      by strengthening synapses but also by enhancing their efficacy to fire spikes-and
      the two combine to act as an effective substrate for amplifying LTP.

PMID- 22157124
TI  - Task-dependent changes of motor cortical network excitability during precision
      grip compared to isolated finger contraction.
AB  - The purpose of this study was to determine whether task-dependent differences in
      corticospinal pathway excitability occur in going from isolated contractions of
      the index finger to its coordinated activity with the thumb. Focal transcranial
      magnetic stimulation (TMS) was used to measure input-output (I/O) curves--a
      measure of corticospinal pathway excitability--of the contralateral first dorsal
      interosseus (FDI) muscle in 21 healthy subjects performing two isometric motor
      tasks: index abduction and precision grip. The level of FDI electromyographic
      (EMG) activity was kept constant across tasks. The amplitude of the FDI motor
      evoked potentials (MEPs) and the duration of FDI silent period (SP) were plotted
      against TMS stimulus intensity and fitted, respectively, to a Boltzmann sigmoidal
      function. The plateau level of the FDI MEP amplitude I/O curve increased by an
      average of 40% during the precision grip compared with index abduction. Likewise,
      the steepness of the curve, as measured by the value of the maximum slope,
      increased by nearly 70%. By contrast, all I/O curve parameters [plateau, stimulus
      intensity required to obtain 50% of maximum response (S(50)), and slope] of SP
      duration were similar between the two tasks. Short- and long-latency
      intracortical inhibitions (SICI and LICI, respectively) were also measured in
      each task. Both measures of inhibition decreased during precision grip compared
      with the isolated contraction. The results demonstrate that the motor cortical
      circuits controlling index and thumb muscles become functionally coupled when the
      muscles are used synergistically and this may be due, at least in part, to a
      decrease of intracortical inhibition and an increase of recurrent excitation.

PMID- 22157123
TI  - Segmental differences in firing properties and potassium currents in Drosophila
      larval motoneurons.
AB  - Potassium currents play key roles in regulating motoneuron activity, including
      functional specializations that are important for locomotion. The thoracic and
      abdominal segments in the Drosophila larval ganglion have repeated arrays of
      motoneurons that innervate body-wall muscles used for peristaltic movements
      during crawling. Although abdominal motoneurons and their muscle targets have
      been studied in detail, owing, in part, to their involvement in locomotion,
      little is known about the cellular properties of motoneurons in thoracic
      segments. The goal of this study was to compare firing properties among thoracic
      motoneurons and the potassium currents that influence them. Whole-cell, patch
      clamp recordings performed from motoneurons in two thoracic and one abdominal
      segment revealed both transient and sustained voltage-activated K(+) currents,
      each with Ca(++)-sensitive and Ca(++)-insensitive [A-type, voltage-dependent
      transient K(+) current (I(Av))] components. Segmental differences in the
      expression of voltage-activated K(+) currents were observed. In addition, we
      demonstrate that Shal contributes to I(Av) currents in the motoneurons of the
      first thoracic segment.

PMID- 22157125
TI  - Dopaminergic neuromodulation of synaptic transmission between mitral and granule
      cells in the teleost olfactory bulb.
AB  - A growing body of evidence suggests that teleosts are important models for the
      study of neural processing of olfactory information, and the functional role of
      dopamine (DA), which is a potent neuromodulator endogenous to the mammalian
      olfactory bulb, has been one of the strongest focuses in this field. However, the
      cellular mechanisms of dopaminergic neuromodulation in olfactory bulbar neural
      circuits have not been fully understood. We investigated such mechanisms by using
      the goldfish, which offers several advantages for analyzing olfactory information
      processing by electrophysiological methods. First, we found in the olfactory bulb
      that numerous cell bodies of the dopaminergic neurons are mainly distributed in
      the mitral cell layer and extend fine processes to the glomerular layer. Next, we
      made in vitro field potential recordings and showed that synaptic transmissions
      from mitral to granule cells were suppressed by DA application. DA also increased
      the paired-pulse ratio, suggesting that the suppression of synaptic transmission
      is caused by a decrease in presynaptic glutamate release from the mitral cells.
      Furthermore, DA significantly suppressed the oscillatory activity of the
      olfactory bulb in response to olfactory stimuli. Although DA suppresses the
      synaptic inputs from the olfactory nerve to the olfactory bulbar neurons in
      mammals, this phenomenon was not observed in the goldfish. These findings
      indicate that suppression of the mitral to granule cell synaptic transmission in
      the reciprocal synapses plays an important role in the negative regulation of
      olfactory responsiveness in the goldfish olfactory bulb.

PMID- 22157126
TI  - Heterogeneous firing behavior during ictal-like epileptiform activity in vitro.
AB  - Seizure activity in vivo is caused by populations of neurons displaying a high
      degree of variability in activity pattern during the attack. The reason for this
      variability is not well understood. Here we show in an in vitro preparation that
      hippocampal CA1 pyramidal cells display four types of afterdischarge behavior
      during stimulus-induced ictal-like events in the presence of Cs(+) (5 mM): type I
      (43.7%) consisting of high-frequency firing riding on a plateau potential; type
      II (28.2%) consisting of low-frequency firing with no plateau potential; type III
      (18.3%) consisting of high-frequency firing with each action potential preceded
      by a transient hyperpolarization and time-locked to population activity, no
      plateau potential; "passive" (9.9%) typified by no afterdischarge. Type I
      behavior was blocked by TTX (0.2 MUM) and intracellular injection of QX314 (12.5
      25 mM). TTX (0.2 MUM) or phenytoin (50 MUM) terminated ictal-like events,
      suggesting that the persistent Na(+) current (I(NaP)) is pivotal for type I
      behavior. Type I behavior was not correlated to intrinsic bursting capability.
      Blockade of the M current (I(M)) with linopirdine (10 MUM) increased the ratio of
      type I neurons to 100%, whereas enhancing I(M) with retigabine (50-100 MUM)
      greatly reduced the epileptiform activity. These results suggest an important
      role of I(M) in determining afterdischarge behavior through control of I(NaP)
      expression. We propose that type I neurons act as pacemakers, which, through
      synchronization, leads to recruitment of type III neurons. Together, they provide
      the "critical mass" necessary for ictogenesis to become regenerative.

PMID- 22157128
TI  - Precordial thump in a newborn with refractory supraventricular tachycardia and
      cardiovascular collapse after amiodarone administration.

PMID- 22157127
TI  - Electrophysiological recordings in humans reveal reduced location-specific
      attentional-shift activity prior to recentering saccades.
AB  - Being able to effectively explore the visual world is of fundamental importance,
      and it has been suggested that the straight-ahead gaze position within the
      egocentric reference frame ("primary position") might play a special role in this
      context. In the present study we employed human electroencephalography (EEG) to
      examine neural activity related to the spatial guidance of saccadic eye
      movements. Moreover, we sought to investigate whether such activity would be
      modulated by the spatial relation of saccade direction to the primary gaze
      position (recentering saccades). Participants executed endogenously cued saccades
      between five equidistant locations along the horizontal meridian. This design
      allowed for the comparison of isoamplitude saccades from the same starting
      position that were oriented either toward the primary position (centripetal) or
      further away from it (centrifugal). By back-averaging time-locked to the saccade
      onset on each trial, we identified a parietally distributed, negative-polarity
      EEG deflection contralateral to the direction of the upcoming saccade.
      Importantly, this contralateral presaccadic negativity, which appeared to reflect
      the location-specific attentional guidance of the eye movement, was attenuated
      for recentering saccades relative to isoamplitude centrifugal saccades. This
      differential electrophysiological signature was paralleled by faster saccadic
      reaction times and was substantially more apparent when time-locking the data to
      the onset of the saccade rather than to the onset of the cue, suggesting a tight
      temporal association with saccade initiation. The diminished level of this
      presaccadic component for recentering saccades may reflect the preferential
      coding of the straight-ahead gaze position, in which both the eye-centered and
      head-centered reference frames are perfectly aligned and from which the visual
      world can be effectively explored.

PMID- 22157129
TI  - Reperfusion strategies for acute coronary syndrome.

PMID- 22157130
TI  - Long-term follow-up of 2 newborns with a combined birth weight of 540 grams.
AB  - Long-term growth and developmental data are presented for the smallest and third
      smallest surviving newborns in the world literature to 5 and 20 years of age,
      respectively. Both patients exhibited normal motor and language development.
      Although head circumference for both newborns demonstrated catchup growth,
      significant differences in height and weight growth velocities persisted.

PMID- 22157131
TI  - Family-centered program deters substance use, conduct problems, and depressive
      symptoms in black adolescents.
AB  - OBJECTIVES: The present research addressed the following important question in
      pediatric medicine: Can participation in a new family-centered preventive
      intervention, the Strong African American Families-Teen (SAAF-T) program, deter
      conduct problems, substance use, substance use problems, and depressive symptoms
      among rural black adolescents across 22 months? METHODS: Data were collected from
      502 black families in rural Georgia, assigned randomly to SAAF-T or an attention
      control condition. The prevention condition consisted of 5 consecutive meetings
      at community facilities with separate, concurrent sessions for caregivers and
      adolescents followed by a caregiver-adolescent session in which families
      practiced skills they learned in the separate sessions. Adolescents self-reported
      conduct problem behaviors, substance use, substance use problems, and depressive
      symptoms at ages 16 years (pretest) and 17 years 10 months (long-term
      assessment). RESULTS: Adolescents who participated in SAAF-T evinced lower
      increases in conduct problem behavior, substance use, substance use problems, and
      depressive symptom frequencies than did adolescents in the attention control
      condition across the 22 months between pretest and long-term assessment.
      CONCLUSIONS: This is the first study to demonstrate efficacy in a prevention
      program designed to deter conduct problems, substance use, substance use
      problems, and depressive symptoms among rural black adolescents. Because SAAF-T
      is a manualized, structured program, it can be easily disseminated to public
      health agencies, schools, churches, boys' and girls' clubs, and other community
      organizations.

PMID- 22157132
TI  - Trivalent inactivated influenza vaccine is not associated with sickle cell crises
      in children.
AB  - BACKGROUND AND OBJECTIVES: Children with sickle cell disease are considered at
      high risk for complications from influenza infection and are recommended to
      receive annual influenza vaccination. However, data on the safety of influenza
      vaccination in children with sickle cell anemia are sparse. METHODS: Using a
      retrospective cohort of children aged 6 months to 17 years in 8 managed care
      organizations that comprise the Vaccine Safety Datalink and who had a diagnosis
      of sickle cell anemia from 1999 to 2006, we conducted matched case-control and
      self-controlled case series studies to examine the association of trivalent
      inactivated influenza vaccination with hospitalization for sickle cell crisis in
      the 2 weeks after vaccination. RESULTS: From an original pool of 1085 pediatric
      subjects with a diagnosis of sickle cell anemia, we identified 179 children with
      at least 1 sickle cell crisis during any influenza season (October 1-March 31).
      In the matched case-control study (matching on age category, gender, Vaccine
      Safety Datalink site, and season), the odds ratio of hospitalization for a crisis
      in vaccinated compared with unvaccinated children was not significant: 1.3 (95%
      confidence interval 0.8-2.2). In the self-controlled case series study of
      hospitalized cases, the incident rate ratio for hospitalization with sickle cell
      crisis in the 2 weeks after trivalent inactivated influenza vaccination was also
      not significant: 1.2 (95% confidence interval 0.75-1.95). CONCLUSION: This large
      cohort study did not find an association of influenza vaccination and
      hospitalization for sickle cell crises in children with sickle cell anemia.

PMID- 22157133
TI  - Multicentric Castleman disease in an HHV8-infected child born to consanguineous
      parents with systematic review.
AB  - Childhood multicentric Castleman disease (MCD) is a rare and unexplained
      lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected
      child, born to consanguineous Comorian parents, who displayed isolated MCD in the
      absence of any known immunodeficiency. We also systematically review the clinical
      features of the 32 children previously reported with isolated and unexplained
      MCD. The characteristics of this patient and the geographic areas of origin of
      most previous cases suggest that pediatric MCD is associated with HHV-8
      infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood
      may result from inborn errors of immunity to HHV-8 infection.

PMID- 22157134
TI  - Histologic chorioamnionitis is associated with reduced risk of late-onset sepsis
      in preterm infants.
AB  - BACKGROUND: Histologic chorioamnionitis (HCA) is implicated in the onset of
      preterm labor and delivery. Chorioamnionitis is a known risk factor for early
      onset sepsis and may modulate postnatal immunity. Preterm infants are at greatly
      increased risk of late-onset sepsis (LOS), particularly with coagulase-negative
      staphylococci (CoNS), but the impact of HCA on the risk of LOS is unknown.
      METHODS: Eight hundred thirty-eight preterm infants born at <30 weeks gestational
      age at a single tertiary center were included. Histologic examination of placenta
      and extraplacental membranes was performed, and clinical data were extracted from
      hospital databases. The influence of HCA on the incidence of early-onset sepsis
      and LOS was examined using logistic regression analysis and Cox proportional
      hazards regression. RESULTS: Mean gestational age was 26.9 +/- 1.9 weeks, and
      mean birth weight was 936 +/- 277 g. Two hundred and seventy-six (33%) of 838
      infants developed LOS. The presence of fetal or maternal HCA, or maternal HCA and
      fetal HCA alone, was associated with a significantly decreased risk of LOS with
      any organism. Histologic chorioamnionitis correlated with a significantly
      decreased risk of CoNS LOS. CONCLUSIONS: HCA is associated with a significantly
      reduced risk of acquiring LOS, both with CoNS and other bacteria. Perinatal
      inflammation may enhance the functional maturation of the preterm immune system
      and provide protection against LOS in high-risk preterm infants.

PMID- 22157135
TI  - Clinical characteristics and risk factors for symptomatic pediatric gallbladder
      disease.
AB  - OBJECTIVE: Our center previously reported its experience with pediatric
      gallbladder disease and cholecystectomies from 1980 to 1996. We aimed to
      determine the current clinical characteristics and risk factors for symptomatic
      pediatric gallbladder disease and cholecystectomies and compare these findings
      with our historical series. STUDY DESIGN: Retrospective, cross-sectional study of
      children, 0 to 18 years of age, who underwent a cholecystectomy from January 2005
      to October 2008. RESULTS: We evaluated 404 patients: 73% girls; 39% Hispanic and
      35% white. The mean age was 13.10 +/- 0.91 years. The primary indications for
      surgery in patients 3 years or older were symptomatic cholelithiasis (53%),
      obstructive disease (28%), and biliary dyskinesia (16%). The median BMI
      percentile was 89%; 39% were classified as obese. Of the patients with
      nonhemolytic gallstone disease, 35% were obese and 18% were severely obese; BMI
      percentile was 99% or higher. Gallstone disease was associated with hemolytic
      disease in 23% (73/324) of patients and with obesity in 39% (126/324). Logistic
      regression demonstrated older age (P = .019) and Hispanic ethnicity (P < .0001)
      as independent risk factors for nonhemolytic gallstone disease. Compared with our
      historical series, children undergoing cholecystectomy are more likely to be
      Hispanic (P = .003) and severely obese (P < .0279). CONCLUSION: Obesity and
      Hispanic ethnicity are strongly correlated with symptomatic pediatric gallbladder
      disease. In comparison with our historical series, hemolytic disease is no longer
      the predominant risk factor for symptomatic gallstone disease in children.

PMID- 22157136
TI  - The natural course of infantile spinal muscular atrophy with respiratory distress
      type 1 (SMARD1).
AB  - BACKGROUND: Only scarce information is available on the long-term outcome and the
      natural course of children with infantile spinal muscular atrophy with
      respiratory distress type 1 (SMARD1) due to mutations in the IGHMBP2 gene.
      OBJECTIVE: To describe the natural disease course, to systematically quantify the
      residual capacities of children with SMARD1 who survive on permanent mechanical
      respiration, and to identify markers predicting the disease outcome at the time
      of manifestation. METHODS: We conducted a longitudinal study of 11 infantile
      SMARD1 patients over a mean observational period of 7.8 (SD 3.2) years. Disease
      specific features were continuously assessed by using a semiquantitative scoring
      system. Additionally, we analyzed the residual enzymatic activity of 6 IGHMBP2
      mutants in our patients. RESULTS: After an initial rapid decline of the clinical
      score until the age of 2 years, residual capabilities reached a plateau or even
      improved. The overall clinical outcome was markedly heterogeneous, but clinical
      scores at the age of 3 months showed a positive linear correlation with the
      clinical outcome at 1 year and at 4 years of age. If expressed in an in vitro
      recombinant system, mutations of patients with more favorable outcomes retained
      residual enzymatic activity. CONCLUSIONS: Despite their severe disabilities and
      symptoms, most SMARD1 patients are well integrated into their home environment
      and two thirds of them are able to attend kindergarten or school. This
      information will help to counsel parents at the time of disease manifestation.

PMID- 22157137
TI  - Peer-led education for adolescents with asthma in Jordan: a cluster-randomized
      controlled trial.
AB  - OBJECTIVES: To determine the impact of a peer-led education program, developed in
      Australia, on health-related outcomes in high school students with asthma in
      Jordan. METHODS: In this cluster-randomized controlled trial, 4 high schools in
      Irbid, Jordan, were randomly assigned to receive the Adolescent Asthma Action
      program or standard practice. Bilingual health workers trained 24 peer leaders
      from Year 11 to deliver asthma education to younger peers from Year 10 (n = 92),
      who in turn presented brief asthma skits to students in Years 8 and 9 (n = 148)
      and to other members of the school community in the intervention schools.
      Students with asthma (N = 261) in Years 8, 9, and 10 completed baseline surveys
      in December 2006 and 3 months after the intervention. RESULTS: Students from the
      intervention group reported clinically significant improvements in health-related
      quality of life (mean difference: 1.35 [95% confidence interval: 1.04-1.76]),
      self-efficacy to resist smoking (mean difference: 4.63 [95% confidence interval:
      2.93-6.35]), and knowledge of asthma self- management (mean difference: 1.62 [95%
      confidence interval: 1.15-2.19]) compared with the control group. CONCLUSIONS:
      This trial demonstrated that the Adolescent Asthma Action program can be readily
      adapted to suit different cultures and contexts. Adolescents in Jordan were
      successful in teaching their peers about asthma self-management and motivating
      them to avoid smoking. The findings revealed that peer education can be a useful
      strategy for health promotion programs in Jordanian schools when students are
      given the opportunity and training.

PMID- 22157138
TI  - Identifying quality improvement opportunities in a universal newborn hearing
      screening program.
AB  - BACKGROUND AND OBJECTIVES: Hospital-based universal newborn hearing screening
      (UNHS) programs are encouraged to maintain quality assurance protocols, but many
      hospitals lack the time and resources to initiate this process. We studied a
      practical approach to measuring baseline quality indicators and identifying
      improvement opportunities in UNHS programs. METHODS: We determined screening
      processes and quality indicators for UNHS programs at 4 hospitals through site
      visits and a 2-year retrospective review of nursery and audiology records.
      Nurses, audiologists, and otolaryngologists met for feedback of hospital-specific
      quality indicators. The sessions identified improvement opportunities and
      proposed system changes for immediate implementation. RESULTS: Hospitals screened
      21 957 newborns for hearing loss. Screening rates were >99% at all hospitals.
      Rates of referral and diagnostic testing varied significantly between hospitals.
      Low referral rates prompted 2 hospitals to adjust screening processes to reduce
      potential false-negative screening results. Two other hospitals addressed poor
      diagnostic follow-up by changing the referral process to include additional
      family contact information. Hospitals also increased referrals to Early
      Intervention Child Find services on the basis of our finding that these referrals
      increased the likelihood of diagnostic follow-up fourfold. We could not fully
      assess indicators of hearing aid eligibility and enrollment in early intervention
      services due to insufficient documentation. CONCLUSIONS: Review of nursery and
      audiology records successfully established most quality indicators for the UNHS
      programs we studied. Feedback of quality indicators identified multiple
      improvement opportunities and facilitated endorsement of immediate system
      changes. This study demonstrates a practical and data-driven approach to quality
      improvement that can be used by any UNHS program.

PMID- 22157139
TI  - Preterm birth alters the maturation of baroreflex sensitivity in sleeping
      infants.
AB  - OBJECTIVE: Impaired blood pressure (BP) control may underpin the increased
      incidence of the sudden infant death syndrome (SIDS) in preterm infants. This
      study aimed to examine the effects of preterm birth, postnatal age, and sleep
      state on BP control by measuring baroreflex sensitivity (BRS) across the first 6
      months of term-corrected age (CA), when SIDS risk is greatest. METHODS: Preterm
      (n = 25) and term (n = 31) infants were studied longitudinally at 2 to 4 weeks, 2
      to 3 months, and 5 to 6 months CA using daytime polysomnography. BP was recorded
      during quiet (QS) and active (AS) sleep using a photoplethysmographic cuff placed
      around the infant's wrist (Finometer [FMS, Finapres Medical Systems, Amsterdam,
      Netherlands]). BRS (milliseconds/mm Hg) was assessed in 1- to 2-minute epochs
      using cross-spectral analysis. RESULTS: In preterm infants, postnatal age had no
      significant effect on BRS within either QS or AS. This was in contrast to the
      maturational increase in QS observed in term infants. Compared with term infants,
      BRS of preterm infants was 38% higher at 2 to 4 weeks CA and 29% lower at 5 to 6
      months CA during QS (P <.05). Comparing sleep states, BRS of preterm infants was
      26% lower in QS compared with AS at 2 to 3 months CA (P <.05). CONCLUSIONS:
      Preterm birth impairs the normal maturational increase in BRS, resulting in a
      substantial reduction in BRS at 5 to 6 months CA during QS. Lower BRS during QS
      compared with AS at 2 to 3 months CA may place preterm infants at an increased
      risk for cardiovascular instability at this age of peak incidence of SIDS.

PMID- 22157140
TI  - Ranitidine is associated with infections, necrotizing enterocolitis, and fatal
      outcome in newborns.
AB  - BACKGROUND AND OBJECTIVES: Gastric acidity is a major nonimmune defense mechanism
      against infections. The objective of this study was to investigate whether
      ranitidine treatment in very low birth weight (VLBW) infants is associated with
      an increased risk of infections, necrotizing enterocolitis (NEC), and fatal
      outcome. METHODS: Newborns with birth weight between 401 and 1500 g or
      gestational age between 24 and 32 weeks, consecutively observed in neonatal
      intensive care units, were enrolled in a multicenter prospective observational
      study. The rates of infectious diseases, NEC, and death in enrolled subjects
      exposed or not to ranitidine were recorded. RESULTS: We evaluated 274 VLBW
      infants: 91 had taken ranitidine and 183 had not. The main clinical and
      demographic characteristics did not differ between the 2 groups. Thirty-four
      (37.4%) of the 91 children exposed to ranitidine and 18 (9.8%) of the 183 not
      exposed to ranitidine had contracted infections (odds ratio 5.5, 95% confidence
      interval 2.9-10.4, P < .001). The risk of NEC was 6.6-fold higher in ranitidine
      treated VLBW infants (95% confidence interval 1.7-25.0, P = .003) than in control
      subjects. Mortality rate was significantly higher in newborns receiving
      ranitidine (9.9% vs 1.6%, P = .003). CONCLUSIONS: Ranitidine therapy is
      associated with an increased risk of infections, NEC, and fatal outcome in VLBW
      infants. Caution is advocated in the use of this drug in neonatal age.

PMID- 22157141
TI  - Prognostic models for stillbirth and neonatal death in very preterm birth: a
      validation study.
AB  - OBJECTIVES: To validate externally 2 prognostic models for stillbirth and
      neonatal death in very preterm infants who are either known to be alive at the
      onset of labor or admitted for neonatal intensive care. PATIENTS AND METHODS: All
      infants, with gestational age 22 to 32 weeks, of European ethnicity, known to be
      alive at the onset of labor (n = 17 582) and admitted for neonatal intensive care
      (n = 11 578), who were born in the Netherlands between January 1, 2000, and
      December 31, 2007. The main outcome measures were stillbirth or death within 28
      days for infants known to be alive at the onset of labor and death before
      discharge from the NICU for infants admitted for intensive care. Model
      performance was studied with calibration plots and c statistic. RESULTS: Of the
      infants known to be alive at the onset of labor, 16.7% (n = 2939) died during
      labor or within 28 days of birth, and 7.8% (n = 908) of the infants admitted for
      neonatal intensive care died before discharge from intensive care. The prognostic
      model for infants known to be alive at the onset of labor showed good calibration
      and excellent discrimination (c statistic 0.92). The prognostic model for infants
      admitted for neonatal intensive care showed good calibration and good
      discrimination (c statistic 0.82). CONCLUSIONS: The 2 prognostic models for
      stillbirth and neonatal death in very preterm Dutch infants showed good
      performance, suggesting their use in clinical practice in the Netherlands and
      possibly other Western countries.

PMID- 22157142
TI  - Maternal ethanol consumption by pregnant guinea pigs causes neurobehavioral
      deficits and increases ethanol preference in offspring.
AB  - The objective of this study was to test the hypothesis that prenatal exposure to
      ethanol, through maternal consumption of an aqueous ethanol solution, induces
      neurobehavioral deficits and increases ethanol preference in offspring. Pregnant
      Dunkin-Hartley-strain guinea pigs were given 24-h access to an aqueous ethanol
      solution (5%, v/v) sweetened with sucralose (1 g/l), or water sweetened with
      sucralose (1 g/l), throughout gestation. Spontaneous locomotor activity was
      measured in the offspring on postnatal day (PD) 10. The offspring underwent
      either ethanol preference testing using a two-bottle-choice paradigm beginning on
      PD 40 or Morris water maze testing using a hidden moving platform design
      beginning on PD 60. Maternal consumption of a 5% (v/v) ethanol solution (average
      daily dose of 2.3+/-0.1 g of ethanol/kg maternal body weight; range: 1.8-2.8
      g/kg) decreased offspring birth weight, increased spontaneous locomotor activity,
      and increased preference for an aqueous ethanol solution. In the Morris water
      maze test, sucralose-exposed offspring decreased escape latency on the second day
      of testing, whereas the ethanol-exposed offspring showed no improvement. These
      data demonstrate that moderate maternal consumption of ethanol produces
      hyperactivity, enhances ethanol preference, and impairs learning and memory in
      guinea pig offspring.

PMID- 22157143
TI  - Contextual and behavioral control of antipsychotic sensitization induced by
      haloperidol and olanzapine.
AB  - Repeated administration of haloperidol (HAL) and olanzapine (OLZ) causes a
      progressively enhanced disruption of the conditioned avoidance response (CAR) and
      a progressively enhanced inhibition of phencyclidine (PCP)-induced
      hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are
      thought to reflect intrinsic antipsychotic activity. The present study examined
      the extent to which antipsychotic-induced sensitization in one model (e.g. CAR)
      can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means
      of investigating the contextual and behavioral controls of antipsychotic
      sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested
      in the CAR or the PCP (3.2 mg/kg, subcutaneously) hyperlocomotion model under HAL
      or OLZ for 5 consecutive days. Then they were switched to the other model and
      tested for the expression of sensitization. Finally, all rats were switched back
      to the original model and retested for the expression of sensitization. Repeated
      HAL or OLZ treatment progressively disrupted avoidance responding and decreased
      PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a
      different model, rats previously treated with HAL or OLZ did not show a stronger
      inhibition of CAR-induced or PCP-induced hyperlocomotion than those treated with
      these drugs for the first time; however, they did show such an effect when tested
      in the original model in which they received repeated antipsychotic treatment.
      These findings suggest that the expression of antipsychotic sensitization is
      strongly influenced by the testing environment and/or selected behavioral
      response under certain experimental conditions. Distinct contextual cues and
      behavioral responses may develop an association with unconditional drug effects
      through a Pavlovian conditioning process. They may also serve as occasion setters
      to modulate the expression of sensitized responses. As antipsychotic
      sensitization mimics the clinical effects of antipsychotic treatment,
      understanding the neurobiological mechanisms of antipsychotic sensitization and
      its contextual control would greatly enhance our understanding of the
      psychological and neurochemical nature of antipsychotic treatment in the clinic.

PMID- 22157144
TI  - Environmental enrichment protects against the acquisition of cocaine self
      administration in adult male rats, but does not eliminate avoidance of a drug
      associated saccharin cue.
AB  - One of the most menacing consequences of drug addiction is the devaluation of
      natural rewards (e.g. food, sex, work, money, caring for one's offspring).
      However, evidence also suggests that natural rewards, such as an enriched
      environment, can devalue drugs of abuse. Thus, this study used a rodent model to
      test whether exposure to an enriched environment could protect adult rats from
      acquiring cocaine self-administration and from the resultant drug-induced
      devaluation of a natural saccharin reward cue. Adult male Sprague-Dawley rats
      were implanted with intravenous jugular catheters. Rats were then separated into
      two housing conditions: an enriched condition, including social
      companions(four/cage) and novel objects (e.g. balls, polyethylene tubes, paper,
      etc.), and a nonenriched condition where the rats were singly housed with no
      novel objects. During testing, the rats were given 5-min access to 0.15%
      saccharin, followed by 1 h to self-administer saline or cocaine (0.167
      mg/infusion) on fixed ratio and progressive ratio schedules of reinforcement. The
      results showed that rats that were singly housed in the nonenriched environment
      fell into two groups: low drug-takers (n=34) and high drug-takers (n=12). In
      comparison, only one out of the 22 rats housed in the enriched environment was a
      high drug-taker. Thus, all rats in the enriched environment, except one, behaved
      like low drug-takers under the nonenriched condition. As such, these rats self
      administered almost no drug on either the fixed ratio or the progressive ratio
      schedule of reinforcement and were extremely slow to self-administer their first
      cocaine infusion. Interestingly, despite their very low levels of drug self
      administration, low-drug-taking rats housed in the enriched environment continued
      to avoid intake of the drug-associated saccharin cue. Taken together, these data
      suggest that the enriched environment itself served as a salient natural reward
      that reduced cocaine seeking and cocaine taking, but had little impact on
      avoidance of the cocaine-paired taste cue. The protective effects of the enriched
      environment were robust and, as such, have important implications for the methods
      used in the study of drug addiction in animal models and for the prevention, and
      possibly the treatment, of the disease in adult humans.

PMID- 22157145
TI  - Improved working memory following novel combinations of physical and cognitive
      activity.
AB  - BACKGROUND: In humans, retrospective studies suggest that habitual physical
      activity (PA) or cognitive activity (CA) can help maintain or improve cognitive
      function. Similar findings have been reported using physical exercise in animal
      studies; however, the exercise paradigms differ markedly in duration and
      frequency, making extrapolation difficult. Here, the authors present a novel PA
      and CA paradigm that combines voluntary wheel running with Hebb-Williams and
      radial arm maze (RAM) training. METHODS: A total of 57 male Sprague-Dawley rats
      were divided into 4 treatment groups: the PA, CA, and combined PA and CA groups
      and sedentary controls. PA (voluntary wheel running) and CA (Hebb-Williams mazes)
      consisted of a moderate 2 h/d, 5 d/wk treatment paradigm. RESULTS: Animals
      exposed to a combination of PA and CA made significantly fewer working memory
      errors and exhibited superior choice accuracy when compared with animals exposed
      to either PA or CA alone in the 8-arm baited configuration of the RAM. Additional
      analyses revealed that the cognitive improvements were independent of exercise
      intensity/duration. Assessment of brain-derived neurotrophic factor (BDNF) levels
      revealed a significant increase in hippocampal BDNF only in the PA-alone group.
      CONCLUSION: A novel combination of PA and CA improves learning and memory
      abilities independent of activity intensity, BDNF, or phosphorylated cyclic AMP
      response element binding protein levels. This is the first report of significant
      changes in cognitive ability using a paradigm involving moderate levels of PA
      plus cognitive stimulation. An adaptation of this paradigm may be particularly
      beneficial in slowing the development of mild cognitive impairment and subsequent
      dementia in elderly people.

PMID- 22157146
TI  - Functional and physiological effects of treadmill training induced by buspirone,
      carbidopa, and L-DOPA in clenbuterol-treated paraplegic mice.
AB  - BACKGROUND: Chronic spinal cord injury may be complicated by weight loss, muscle
      atrophy, and bone loss. OBJECTIVE: The authors identified a combination
      pharmacotherapy using buspirone, carbidopa, and L-DOPA (BCD) that elicits bouts
      of locomotor-like movements in spinal cord-transected (Tx) mice. They then
      evaluated the effects of 8 weeks of treadmill training in Tx mice that received
      BCD or BCD + clenbuterol, a monoaminergic agent with anabolic properties, on
      locomotor function, muscle atrophy, adipose tissue loss, and bone density
      measures. METHODS: Induced locomotor movement, adipose tissue, skeletal muscle,
      and femoral bone properties were compared in unoperated control mice, operated
      controls (untreated, untrained Tx mice), and 2 groups of treated, trained Tx mice
      (Tx + BCD, Tx + BCD + clenbuterol) that also received training. RESULTS: BCD- and
      BCD + clenbuterol-treated mice showed comparable levels of locomotor movements
      that significantly improved over time. Soleus muscle mass and soleus and extensor
      digitorum longus cross-sectional area significantly increased in both groups of
      BCD-treated mice, with greater effects in BCD + clenbuterol-treated animals.
      Fiber type conversion, adipose tissues, bone mineral density, and content were
      reduced in all Tx groups compared with unoperated control mice. CONCLUSION: These
      findings suggest that locomotor movement and muscle properties can be restored to
      near-normal levels after several weeks of BCD treatment, regular training, and
      clenbuterol in completely paraplegic animals.

PMID- 22157147
TI  - Botulinum toxin effect on voluntary and stretch reflex-related torque produced by
      the quadriceps: an isokinetic pilot study.
AB  - BACKGROUND: An understanding of the mechanical effects of botulinum toxin type A
      (BoNT A) on spastic and voluntary muscle contraction may help predict functional
      responders. OBJECTIVE: To compare the effect of BoNT A on the voluntary and
      stretch reflex-related torques produced by activation of the rectus femoris (RF).
      METHODS: This was a prospective open study where 15 incomplete spinal cord injury
      patients, impaired by a stiff-knee gait, with RF hyperactivity in mid-swing
      quantified by formal gait analysis (GA), were assessed before and after RF BoNT A
      injection (Botox, 200 UI). MAIN OUTCOME MEASURES: Included isokinetic peak torque
      (and angle at peak torque) at 0 degrees  (supine) and 90 degrees  (seated) during
      passive stretch (10 deg/s, 90 deg/s, and 150 deg/s), and voluntary contraction
      (60 deg/s) of the quadriceps. Secondary measures included impairment by Modified
      Tardieu Scale (MTS), peak knee flexion and spatial-temporal data by GA, activity
      (6-minute walking test, timed stair climbing), and discomfort (Verbal Rating
      Scale). RESULTS: Voluntary torque decreased (-16%; P = .0004) but with only a
      trend toward a decrease in stretch reflex-related torque. The angle at spastic
      torque increased at 90 deg/s (+5 degrees ; P = .03), whereas MTS, peak knee
      flexion (+4 degrees ; P = .01), spatial-temporal data, timed stair climbing test
      (25%; P = .02), and discomfort were significantly improved. CONCLUSION: BoNT A
      appeared to delay the stretch-reflex angle at peak torque, whereas the voluntary
      torque decreased. After strict patient selection, BoNT A injection into the RF
      muscle led to improvements in impairment, activity, and discomfort.

PMID- 22157149
TI  - Cardiac and gastrointestinal liabilities caused by deficiency in the immune
      modulatory enzyme indoleamine 2,3-dioxygenase.
AB  - Indoleamine 2,3-dioxygenase (IDO) modifies adaptive immunity, in part by
      determining the character of inflammatory responses in the tissue
      microenvironment. Small molecule inhibitors of IDO are being developed to treat
      cancer, chronic infections and other diseases, so the systemic effects of IDO
      disruption on inflammatory phenomena may influence the design and conduct of
      early phase clinical investigations of this new class of therapeutic agents.
      Here, we report cardiac and gastrointestinal phenotypes observed in IDO deficient
      mice that warrant consideration in planned assessments of the safety risks
      involved in clinical development of IDO inhibitors. Calcification of the cardiac
      endometrium proximal to the right ventricle was a sexually dimorphic strain
      specific phenotype with ~30% penetrance in BALB/c mice lacking IDO.
      Administration of complete Freund's adjuvant containing Toll-like receptor
      ligands known to induce IDO caused acute pancreatitis in IDO deficient mice, with
      implications for the design of planned combination studies of IDO inhibitors with
      cancer vaccines. In an established model of hyperlipidemia, IDO deficiency caused
      a dramatic elevation in levels of serum triglycerides. In the large intestine,
      IDO loss only slightly increased sensitivity to induction of acute colitis, but
      it markedly elevated tumor incidence, multiplicity and staging during
      inflammatory colon carcinogenesis. Together, our findings suggest potential
      cardiac and gastrointestinal risks of IDO inhibitors that should be monitored in
      patients as this new class of drugs enter early clinical development.

PMID- 22157151
TI  - Allergic diseases and asthma:  a major global health concern.

PMID- 22157150
TI  - Aurora A mediates cross-talk between N- and C-terminal post-translational
      modifications of p53.
AB  - The serine/threonine protein kinase Aurora A is known to interact with and
      phosphorylate tumor suppressor p53 at Serine 215 (S215), inhibiting the
      transcriptional activity of p53. We show that Aurora A positively regulates human
      p53 protein levels and, using isogenic p53 wild-type and p53-null colorectal
      carcinoma cells, further show that p53 regulates human Aurora A protein
      expression. S215 is located in the DNA-binding core of p53 and at the center of
      the cryptic epitope for PAb240 antibody, which is used to detect mutant and
      denatured p53. Following denaturing SDS PAGE, the PAb240 epitope was detectable
      by immunoblotting in only two out of eight cell lines. The efficacy of novel p53
      targeted anticancer therapies may be influenced by the conformational state of
      p53, therefore, the initial determination of p53 status may be relevant. We found
      no correlation between phosphorylation of p53 at S215 and PAb240 antibody
      recognition. However, phosphorylation at S37 was positively associated with
      PAb240 reactivity. More importantly, we provide the first evidence of Aurora A
      mediated cross-talk between N- and C-terminal p53 post-translational
      modifications. As p53 and Aurora A are targets for anticancer therapy the impact
      of their reciprocal relationship and Aurora A-induced post-translational
      modification of p53 should be considered.

PMID- 22157148
TI  - The Akt signaling pathway: an emerging therapeutic target in malignant melanoma.
AB  - Studies using cultured melanoma cells and patient tumor biopsies have
      demonstrated deregulated PI3 kinase-Akt3 pathway activity in ~70% of melanomas.
      Furthermore, targeting Akt3 and downstream PRAS40 has been shown to inhibit
      melanoma tumor development in mice. Although these preclinical studies and
      several other reports using small interfering RNAs and pharmacological agents
      targeting key members of this pathway have been shown to retard melanoma
      development, analysis of early Phase I and Phase II clinical trials using
      pharmacological agents to target this pathway demonstrate the need for (1)
      selection of patients whose tumors have PI3 kinase-Akt pathway deregulation, (2)
      further optimization of therapeutic agents for increased potency and reduced
      toxicity, (3) the identification of additional targets in the same pathway or in
      other signaling cascades that synergistically inhibit the growth and progression
      of melanoma, and (4) better methods for targeted delivery of pharmaceutical
      agents inhibiting this pathway. In this review we discuss key potential targets
      in PI3K-Akt3 signaling, the status of pharmacological agents targeting these
      proteins, drugs under clinical development, and strategies to improve the
      efficacy of therapeutic agents targeting this pathway.

PMID- 22157152
TI  - Obesity and asthma disease phenotypes.
AB  - PURPOSE OF REVIEW: The increasing prevalence of both asthma and obesity is
      associated with substantial morbidity and healthcare utilization. Herein, we
      review recent data suggesting that the obese asthmatic may represent a distinct
      clinical phenotype. RECENT FINDINGS: Obesity is a major risk factor for asthma,
      and asthma in obese patients appears to be more difficult to control, with
      decreased responsiveness to controller therapies posing a significant public
      health issue, as the prevalence of both asthma and obesity continues to rise.
      Epidemiologic research has defined the association between obesity and asthma, an
      association in part influenced by physiologic abnormalities attendant to both
      disorders. Healthcare utilization is also increased in obese asthmatic
      individuals, with reduced response to asthma controller therapies, a finding
      likely mediated by specific aspects of systemic and airway inflammation. We end
      by reviewing the role of comorbid clinical disorders in the association and by
      highlighting evidence that weight loss is associated with improvement in clinical
      and physiologic parameters of asthma. SUMMARY: Obesity has a significant impact
      on asthma risk, severity and control. Additional studies are needed to define
      mechanisms by which airway physiologic and inflammatory phenotypes in asthma are
      modified by obesity.

PMID- 22157153
TI  - The potential use of tyrosine kinase inhibitors in severe asthma.
AB  - PURPOSE OF REVIEW: Severe asthma comprises heterogeneous phenotypes that share in
      common a poor response to traditional therapies. Recent and ongoing work with
      tyrosine kinase inhibitors suggests a potential beneficial role in treatment of
      severe asthma. RECENT FINDINGS: Various receptor and nonreceptor tyrosine kinase
      pathways contribute to aspects of airway inflammation, airway
      hyperresponsiveness, and remodeling of asthma. Selective and nonselective
      tyrosine kinase inhibitors may be useful to block pathways that are
      pathologically overactive or overexpressed in severe asthma. Recent in-vivo
      studies have demonstrated the utility of inhibitors against specific tyrosine
      kinases (epidermal growth factor receptor, c-kit/platelet derived growth factor
      receptor, vascular endothelial growth factor receptor, spleen tyrosine kinase,
      and janus kinase) in altering key aspects of severe asthma. SUMMARY: Asthma and
      even severe asthma does not consist of a single phenotype. Targeting key
      inflammatory and remodeling pathways engaged across subphenotypes with tyrosine
      kinase inhibitors appears to hold promise.

PMID- 22157154
TI  - Exposure to biomass smoke as a cause for airway disease in women and children.
AB  - PURPOSE OF REVIEW: An estimated 3 billion people (about half the world's
      population) burn biomass fuel (wood, crop residues, animal dung and coal) for
      cooking and heating purposes exposing a large population, especially women and
      children, to high levels of indoor air pollution. Biomass smoke comprises gaseous
      air pollutants as well as particulate matter air pollutants, which have
      significant harmful effects. RECENT FINDINGS: Exposure to biomass smoke is a
      major contributor to morbidity and mortality. Children, women and the elderly are
      most affected. Apart from poor lung growth seen in growing children, the risk of
      developing respiratory tract infections (both upper as well as lower) is greatly
      increased in children living in homes using biomass. Women who spend many hours
      cooking food in poorly ventilated homes develop chronic obstructive lung disease
      (COPD), asthma, respiratory tract infections, including tuberculosis and lung
      cancer. It has been argued that exposure to biomass fuel smoke is a bigger risk
      factor for COPD than tobacco smoking. SUMMARY: Physicians need to be aware about
      the harmful effects of biomass smoke exposure and ensure early diagnosis and
      appropriate management to reduce the disease burden. More research needs to be
      done to study health effects due to biomass smoke exposure better. Reducing the
      exposure to biomass smoke through proper home ventilation, home design and, if
      possible, change of biomass to cleaner fuels is strongly recommended in order to
      reduce biomass smoke-induced mortality and morbidity.

PMID- 22157155
TI  - The role and regulation of microRNAs in asthma.
AB  - PURPOSE OF REVIEW: Asthma is a common chronic inflammatory airway disorder that
      is characterized by variable and recurring airflow obstruction, chronic airway
      inflammation and bronchial hyper-responsiveness. The etiopathogenesis of asthma
      remains a complex issue. The intricacy in developing a more effective therapeutic
      strategy may be due to a large diversity in causative agents and a lack of
      understanding of the precise molecular mechanism involved in asthma. However,
      recent identification of microRNAs (miRs) has enhanced technological abilities to
      understand the disease process. RECENT FINDINGS: miRs regulate gene expression by
      controlling the translation of a specific type of messenger RNA. miRs have been
      recently identified as key regulatory RNAs with immense significance in numerous
      biological processes including asthma. miRs have been implicated to have a
      fundamental role in acute and chronic asthma and in airway remodeling by the
      regulation of multiple signal transduction pathways that are involved in the
      pathogenesis of asthma. It is possible that miRs may bring a fundamental change
      to our understanding of the pathophysiology of asthma. This may then lead to the
      development of novel efficacious therapeutic strategies in asthma. SUMMARY: In
      this review, we highlight the current understanding of the role and regulation of
      miRs in asthma.

PMID- 22157156
TI  - Sex and atopy influences on the natural history of rhinitis.
AB  - PURPOSE OF REVIEW: Rhinitis is a common condition associated with significant
      under-recognized morbidity and impaired quality of life. The natural history of
      rhinitis is poorly characterized. Better understanding of its natural history and
      associated risk factors would improve the ability to effectively manage rhinitis
      in clinical practice. This review focuses on the current research findings on the
      natural history of rhinitis and how that is influenced by atopy and sex. RECENT
      FINDINGS: Recent work from the Isle of Wight Birth Cohort Study has demonstrated
      that the prevalence of atopic rhinitis increases steadily in the first 18 years
      of life in both sexes. However, nonatopic rhinitis behaves differently during
      adolescence. Its prevalence decreases in boys but continues to increase in girls
      resulting in a female predominance after puberty. Numerous recent studies have
      proposed potential roles for sex-related and adipose-related hormonal changes in
      influencing the course of allergic disease. Further research is needed to
      establish mechanisms that could underlie such findings. SUMMARY: Rhinitis becomes
      increasingly common through childhood, with prevalence during adolescence being
      mediated by differential effects of sex and atopy. Mechanisms to explain these
      findings await elucidation.

PMID- 22157157
TI  - New insights into pathogenesis of exercise-induced bronchoconstriction.
AB  - PURPOSE OF REVIEW: Exercise-induced bronchoconstriction (EIB) refers to acute
      airflow obstruction that is triggered by a period of physical exertion. Here we
      review recent findings about the epidemiology of EIB, immunopathology leading to
      EIB, and the latest understanding of the pathogenesis of EIB. RECENT FINDINGS:
      Longitudinal studies demonstrated that airway hyper-responsiveness to exercise or
      cold air at an early age are among the strongest predictors of persistent asthma.
      Patients that are susceptible to EIB have epithelial disruption and increased
      levels of inflammatory eicosanoids such as cysteinyl leukotrienes (CysLT)s. The
      leukocytes implicated in production of eicosanoids in the airways include both a
      unique mast cell population as well as eosinophils. A secreted phospholipase A(2)
      (sPLA(2)) enzyme that serves as a regulator of CysLT formation is present in
      increased quantities in asthma. Transglutaminase 2 (TGM2) is expressed at
      increased levels in asthma and serves as a regulator of secreted phospholipase
      A(2) group X (sPLA(2)-X). Further, sPLA(2)-X acts on target cells such as
      eosinophils to initiate cellular eicosanoid synthesis. SUMMARY: Recent studies
      have advanced our understanding of EIB as a syndrome that is caused by the
      increased production of inflammatory eicosanoids. The airway epithelium may be an
      important regulator of the production of inflammatory eicosanoids by leukocytes.

PMID- 22157159
TI  - T-cell responses during allergen-specific immunotherapy.
AB  - PURPOSE OF REVIEW: Allergen-specific immunotherapy is the only specific, dose
      dependent and time-dependent and disease-modifying strategy for the treatment of
      allergy associated with clinical improvement and biological tolerance which may
      persist years after discontinuation. RECENT FINDINGS: Successful immunotherapy in
      respiratory allergy is associated with the immunodeviation of Th2 response to a
      more protective allergen-specific Th1 cells and with the induction of interleukin
      10 (IL-10)/transforming growth factor (TGF)-beta-producing T regulatory cells in
      blood and inflamed airways. Subcutaneous treatment and sublingual treatments
      induce similar alterations which are dose-dependent and time-dependent. SUMMARY:
      This study provides an update on the immunological T-cell responses during
      subcutanous immunotherapy and sublingual immunotherapy, giving a unifying view of
      the redirecting mechanisms and regulating mechanisms elicited by these
      treatments.

PMID- 22157158
TI  - Alteration of the nasal responses to influenza virus by tobacco smoke.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight recent data
      regarding the impact of exposure to tobacco smoke on influenza virus infection.
      This is timely because of the continuing pattern for influenza to cause epidemics
      and pandemics. RECENT FINDINGS: Experimental animal studies suggest tobacco smoke
      increases severity of respiratory disease with influenza. The interaction is
      complex and dependent on dose and chronicity of both virus and smoke exposure.
      Smoke-induced oxidant stress and suppression of innate immunity are mechanistic
      factors leading to worse disease. Experiments using human respiratory cells show
      that tobacco smoke increases viral replication through mechanisms including
      suppression of antiviral pathways and altered cytokine patterns in cell types
      with central roles in mucosal innate immunity, such as epithelium, dendritic
      cells, and natural killer cells. Studies also suggest a role for antioxidant
      strategies in reducing risk. Human volunteer studies using live attenuated
      influenza virus as a model appear to corroborate many of these findings. SUMMARY:
      Exposure to tobacco smoke remains extremely prevalent worldwide. Although
      avoidance of exposure is a primary goal, it is important to understand the
      mechanisms underlying increased infection risk with tobacco smoke and other
      pollutant exposures, so that novel preventive or treatment strategies can be
      developed.

PMID- 22157160
TI  - Dissecting the role of eosinophil cationic protein in upper airway disease.
AB  - PURPOSE OF REVIEW: Eosinophil granulocyte myeloid cells are increased in atopic
      and nonatopic rhinitis, chronic rhinosinusitis (CRS) and atopic
      keratoconjunctivitis, diseases of the upper respiratory tract. Eosinophils
      contain several basic granule proteins, the best known being the eosinophil
      cationic protein (ECP). ECP is a cytotoxic, pro-fibrotic ribonuclease, which is
      found deposited in these eosinophil-related diseases and is often used in
      parallel with blood eosinophilia to monitor those diseases. The contribution of
      eosinophils and their granule proteins to disease pathogenesis have been debated;
      recent findings might bring these cells to the center of attention. RECENT
      FINDINGS: Novel mediators of atopic disease, interleukin-17 (IL-17) and IL-33
      have been found in the upper respiratory tract. These cytokines stimulate
      eosinophils to survival and degranulation, IL-17 via granulocyte-macrophage
      colony-stimulating factor (GM-CSF), and IL-33 directly. Transforming growth
      factor (TGF)-beta has been found in CRS and atopic keratoconjunctivitis mucosa,
      its production possibly stimulated by ECP. ECP is detected in nasal mucosa of
      local allergic reactions, entopy, in rhinitis and CRS. ECP might be released from
      freely circulating eosinophil granules or in association with eosinophil
      mitochondrial DNA, both means of release for pathogen defence. SUMMARY: Novel
      evidence suggests that eosinophils and ECP might have new prominent roles in
      development of diseases of the upper respiratory tract.

PMID- 22157161
TI  - Managing upper respiratory tract complications of primary ciliary dyskinesia in
      children.
AB  - PURPOSE OF REVIEW: Primary ciliary dyskinesia (PCD) is a rare and heterogeneous
      disease that is often misdiagnosed or diagnosed late with more advanced sequelae.
      PCD primarily effects the respiratory tract, yet most research focuses on the
      lower respiratory tract manifestations, most of which is derived from research on
      cystic fibrosis. Little is known about the management of the upper respiratory
      tract sequelae of PCD. This review summarizes the available evidence for the
      management of otologic and sinonasal manifestations of PCD. RECENT FINDINGS: The
      natural history of otitis media with effusion and hearing loss in PCD appears to
      fluctuate into adulthood and does not resolve by the age of 9 years, regardless
      of treatment, as previously assumed. Ventilation tube insertion improves hearing
      in PCD, but may lead to a higher rate of otorrhoea when compared with the general
      population. Sinonasal disease in PCD is poorly studied; however, it appears that
      patients with chronic rhinosinusitis (CRS) may benefit from long-term macrolide
      therapy and endoscopic sinus surgery (ESS) in recalcitrant disease. Therapies
      targeted at improving mucociliary clearance have not been tested specifically in
      PCD. Pharmacogenetic therapy is currently under investigation to target the
      primary defect in PCD. SUMMARY: Otologic sequeale in PCD should undergo lifelong
      evaluation and monitoring and ventilation tube insertion should be considered to
      avoid complications of chronic hearing loss. Sinonasal disease benefits from
      macrolide therapy and ESS. Randomized controlled trials of treatment efficacy of
      the upper respiratory tract manifestations of PCD are lacking.

PMID- 22157162
TI  - Odontogenic sinusitis:  an ancient but under-appreciated cause of maxillary
      sinusitis.
AB  - PURPOSE OF REVIEW: For well over 100 years, it has been appreciated that
      maxillary dental infections can cause sinusitis. This insight has been largely
      overlooked with the advent of functional endoscopic sinus surgery (ESS) and its
      emphasis on the osteomeatal complex. We review several recent case series and
      reviews of odontogenic sinusitis that characterize and discuss emerging
      diagnostic modalities in odontogenic sinusitis. RECENT FINDINGS: In recent
      publications on odontogenic sinusitis, up to 40% of chronic bacterial maxillary
      sinus infections are attributed to a dental source, which is far higher than the
      previously reported incidence of 10%. Plain dental films and dental evaluations
      frequently fail to detect maxillary dental infection that can be causing
      odontogenic sinusitis. However, sinus computed tomography (CT) or Cone Beam
      Volumetric CT (CBVCT) are far more successful in identifying dental disease
      causing sinusitis. The microbial pathogens of odontogenic sinusitis remain
      unchanged from earlier reviews; however, the clinical findings in odontogenic
      sinusitis are better described in recent reviews. Successful treatment of
      odontogenic sinusitis requires management of the odontogenic source and may
      require concomitant or subsequent sinus surgery. SUMMARY: Odontogenic sinusitis
      is frequently recalcitrant to medical therapy and usually requires treatment of
      the dental disease. Sometimes dental treatment alone is adequate to resolve the
      odontogenic sinusitis and sometimes concomitant or subsequent ESS is required.
      Evaluation of all patients with persistent chronic rhinosinusitis (CRS) should
      include inspection of the maxillary teeth on CT scan for evidence of periapical
      lucencies. Unilateral recalcitrant disease associated with foul smelling drainage
      is especially characteristic of odontogenic sinusitis. High-resolution CT scans
      and CBVCT can assist in identifying dental disease.

PMID- 22157163
TI  - Airway assessment by four-phase rhinomanometry in septal surgery.
AB  - PURPOSE OF REVIEW: This article updates the state of the art in functional
      ventilation tests of the nasal airway. Multidisciplinary international
      cooperation has led within the last years to the development of four-phase
      rhinomanometry (4PR) by eradicating the errors of the 'classic' rhinomanometry.
      RECENT FINDINGS: Physical experiments, mathematical models and comprehensive
      statistical analyses implicate that the nasal breath consists of four phases of
      different diagnostic importance. Presuming the motility of the nasal entrance, it
      is necessary to depict the elastic behavior within the rhinomanometric curve, as
      well as to use new parameters for the clinical evaluation of the nasal
      obstruction. The parameters logarithmic vertex resistance and logarithmic
      effective resistance are related to the sensing of the patient. Their clinical
      importance was proved in studies of more than 12 000 patients. SUMMARY: The human
      eye is not able to estimate the degree of impairment in nasal breathing.
      Therefore, a functional diagnosis is mandatory to avoid unnecessary surgery and
      to control the results. 4PR is a substantial improvement over the currently used
      methods. It should be implemented in the standards of the international
      standardization committee for the objective assessment of the upper airway
      (ISOANA). Practical hints for correct measurements are given.

PMID- 22157164
TI  - Idiopathic rhinitis.
AB  - PURPOSE OF REVIEW: Due to the overlap of symptoms and signs in the various types
      of rhinitis, arriving at a precise diagnosis can be difficult. A diagnosis of
      idiopathic rhinitis can only be used when all other causes have been excluded and
      this review tries to clarify whom this term should be applied to, and the reasons
      why. RECENT FINDINGS: The current literature on idiopathic rhinitis is sparse.
      Haematological and immunological tests can help to distinguish which individuals
      have a predisposition to allergic mediated disease, but these results should be
      interpreted with caution because of the prevalence of false-positives. It has
      recently been shown that some patients previously labelled as 'idiopathic' suffer
      from a highly localized form of IgE-mediated allergy known as 'entopy'. Patients
      with idiopathic rhinitis probably represent a disparate group who may be
      suffering from a range of immunological or neuroregulatory disease processes in
      which an inability to down-regulate inflammatory processes may be as important as
      the process that initiates it. SUMMARY: To arrive at a diagnosis of idiopathic
      rhinitis all other forms of rhinitis must be excluded. With further research and
      a better understanding of the pathological processes involved in rhinitis, we may
      need to use the term 'idiopathic' less frequently but be more assured of its
      correct usage.

PMID- 22157165
TI  - Gastroesophageal reflux and chronic rhinosinusitis.
AB  - PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) and gastroesophageal reflux
      disease (GERD) are two common conditions which have been reported to occur
      together more frequently than expected. It has, therefore, been proposed that
      GERD may have an aetiologic role in CRS. This study reviews the results of
      research into the possible reflux and reflex mechanisms that may link CRS and
      GERD. RECENT FINDINGS: Robust assessment of gastric reflux into the nasopharynx
      using circumferential pH probes which are less subject to artefact have
      demonstrated that direct reflux into the nasopharynx is a rare event. Pepsinogen
      has only been found in the nasal cavity in one study which had unexpected
      results, raising doubts about the validity of the methodology. A reflex increase
      in nasal congestion and mucus secretion has been demonstrated experimentally, but
      in a small number of patients, which precluded statistical significance. The
      relationship between reflux and mucus secretion is supported, though, by
      randomized controlled trials showing decreased postnasal drip with proton-pump
      inhibitor therapy. SUMMARY: Recent evidence suggests that GERD does not play a
      causative role in CRS. However, there is evidence of an oesophageal-nasal reflex,
      particularly in regard to mucus secretion and symptoms of postnasal drip. The
      presence of GERD would, therefore, be expected to worsen nasal symptom scores.

PMID- 22157166
TI  - Fibrous dysplasia of the sinonasal tract and adjacent skull base.
AB  - PURPOSE OF REVIEW: Fibrous dysplasia is a rare condition characterized by
      replacement of normal bone by fibro-osseous connective tissue exhibiting varying
      degrees of osseous metaplasia, which can affect the craniofacial complex. This
      article reviews the recent literature with the intent to highlight the innovative
      information that has contributed to elucidate the pathophysiology, diagnostic
      criteria, and treatment principles of the disease. RECENT FINDINGS: A mutation in
      the GNAS1 gene on chromosome 20 has been identified as the molecular hallmark of
      fibrous dysplasia. This finding is not present in ossifying fibroma, which has
      been traditionally included in differential diagnosis. The concept that
      asymptomatic patients do not require surgical treatment has been reinforced by a
      meta-analysis specifically addressing the issue of optic nerve decompression.
      SUMMARY: A diagnosis of fibrous dysplasia can be achieved by combined assessment
      of clinical, radiologic, and pathologic findings. There is general agreement
      that, when the disease is not associated with symptoms, partial or radical
      resection is not indicated, but patients do require periodic radiologic
      evaluations. There is, however, an absolute need for prospective studies to
      identify factors predicting the possible late growth of the disease and to
      investigate the efficacy and side-effects of pharmacological treatment with
      biphosphonates.

PMID- 22157167
TI  - Role of fungi in pathogenesis of chronic rhinosinusitis:  the hypothesis
      rejected.
AB  - PURPOSE OF REVIEW: Fungi have been suggested to play an important role in the
      pathogenesis of chronic rhinosinusitis (CRS). This review describes the recent
      knowledge concerning the role of fungi in the pathogenesis of CRS and allergic
      fungal rhinosinusitis (AFRS) and the clinical implications for treatment. RECENT
      FINDINGS: Recent studies show that, although there are several potential deficits
      in the innate and potentially also in the acquired immunity of CRS patients that
      might reduce or change their ability to react to fungi, there are not many
      arguments to suggest a causative role for fungi in CRS with or without nasal
      polyps. However, due to the intrinsic or induced change in immunity of CRS
      patients, fungi might have a disease-modifying role. The fact that AFRS is more
      prevalent in warm and humid areas may point to fungi as a factor in this disease.
      SUMMARY: Almost a decade after the launching of the hypothesis by Ponikau, the
      absence of convincing immunological data or evidence for clinical improvement of
      CRS upon therapy with antifungal agents now means that the hypothesis that fungi
      play a role in a majority of the cases of CRS has to be rejected and antifungal
      treatment should not be used.

PMID- 22157168
TI  - Multidisciplinary collaborative gross tumour volume definition for lung cancer
      radiotherapy: a prospective study.
AB  - Variability in gross tumour volume (GTV) definition is a major source of
      systematic error in conformal radiotherapy. This prospective study assesses the
      role of multidisciplinary collaboration between oncologists and radiologists in
      defining lung cancer volumes. Twenty patients with non-small cell lung cancer due
      to receive three-dimensional conformal radiotherapy formed the study population.
      GTVs were defined by a radiologist (GTVrad) and an oncologist (GTVonc) using
      available clinical information and imaging. A collaborative meeting was then held
      to agree on a final, common GTV (GTVfin) to be used for treatment planning, and
      differences analysed. The collaboration changed the GTV in 19/20 patients with a
      total of 50 regions being edited. Changes made were categorized as (a)
      differentiation of tumour from atelectasis or ground glass shadowing, (b)
      separation of tumour from vasculature, and (c) defining mediastinal extent of
      tumour. Oncologists were more confident in the GTVfin than the GTVonc. The
      radiologist took longer to define the GTV than the oncologist. Real-time
      collaborative GTV definition by a radiologist and oncologist is practical and
      feasible. This approach allows specific areas of uncertainty to be categorized
      and focussed on, reducing systematic error in GTV definition. The physician's
      approach to risk and decision making for each patient may also play a role.

PMID- 22157169
TI  - A novel vehicle for transmission of Escherichia coli O157:H7 to humans:
      multistate outbreak of E. coli O157:H7 infections associated with consumption of
      ready-to-bake commercial prepackaged cookie dough--United States, 2009.
AB  - BACKGROUND:  Escherichia coli O157:H7 is a Shiga toxin-producing E. coli (STEC)
      associated with numerous foodborne outbreaks in the United States and is an
      important cause of bacterial gastrointestinal illness. In May 2009, we
      investigated a multistate outbreak of E. coli O157:H7 infections. METHODS: 
      Outbreak-associated cases were identified using serotyping and molecular
      subtyping procedures. Traceback investigation and product testing were performed.
      A matched case-control study was conducted to identify exposures associated with
      illness using age-, sex-, and state-matched controls. RESULTS:  Seventy-seven
      patients with illnesses during the period 16 March-8 July 2009 were identified
      from 30 states; 35 were hospitalized, 10 developed hemolytic-uremic syndrome, and
      none died. Sixty-six percent of patients were <19 years; 71% were female. In the
      case-control study, 33 of 35 case patients (94%) consumed ready-to-bake
      commercial prepackaged cookie dough, compared with 4 of 36 controls (11%)
      (matched odds ratio = 41.3; P < .001); no other reported exposures were
      significantly associated with illness. Among case patients consuming cookie
      dough, 94% reported brand A. Three nonoutbreak STEC strains were isolated from
      brand A cookie dough. The investigation led to a recall of 3.6 million packages
      of brand A cookie dough and a product reformulation. CONCLUSIONS:  This is the
      first reported STEC outbreak associated with consuming ready-to-bake commercial
      prepackaged cookie dough. Despite instructions to bake brand A cookie dough
      before eating, case patients consumed the product uncooked. Manufacturers should
      consider formulating ready-to-bake commercial prepackaged cookie dough to be as
      safe as a ready-to-eat product. More effective consumer education about the risks
      of eating unbaked cookie dough is needed.

PMID- 22157170
TI  - Corticosteroid therapy for liver abscess in chronic granulomatous disease.
AB  - Liver abscesses in chronic granulomatous disease (CGD) are typically difficult to
      treat and often require surgery. We describe 9 X-linked CGD patients with
      staphylococcal liver abscesses refractory to conventional therapy successfully
      treated with corticosteroids and antibiotics. Corticosteroids may have a role in
      treatment of Staphylococcus aureus liver abscesses in CGD.

PMID- 22157171
TI  - An inverse and independent association between Helicobacter pylori infection and
      the incidence of shigellosis and other diarrheal diseases.
AB  - OBJECTIVES:  We examined the association between Helicobacter pylori infection
      and the incidence of diarrheal diseases. METHODS:  In a nested case-control study
      participants were sampled from cohorts of male Israeli soldiers aged 18-21 years,
      serving in field units and followed up for diarrheal diseases. Case patients (n =
      177) were subjects who visited the base clinic because diarrhea and were positive
      for Shigella sonnei (n = 66), enterotoxigenic Escherichia coli (ETEC) (n = 31) or
      negative for bacterial pathogens (n = 80; diarrhea of unknown etiology). Controls
      (n = 418) were subjects who did not suffer from a diarrheal disease during the
      follow-up. They were matched to case patients by training unit and period. Serum
      samples were obtained from participants at the beginning of their field training
      and were tested for anti-H. pylori immunoglobulin (Ig) G and preexisting Shigella
      sonnei lipopolysaccharide IgG and IgA antibodies using enzyme-linked
      immunosorbent assay. RESULTS:  The proportion of H. pylori-infected subjects was
      significantly lower among case patients with infection of unknown etiology
      (36.3%) than among controls (56.0%) (adjusted odds ratio [OR], 0.43; 95%
      confidence interval [CI], .24-.77; P = .005). The proportion of H. pylori
      infected subjects among case patients with S. sonnei shigellosis was also
      significantly lower than in the control group: 36.3% versus 56.0%. The
      association persisted after adjusting for sociodemographic variables and
      preexisting S. sonnei serum IgA antibodies (adjusted OR, 0.37; 95% CI, .14-.95; P
      = .03) and IgG antibodies (adjusted OR, 0.38; 95% CI, .14-.99; P = .04). The
      direction of the association between H. pylori infection and ETEC diarrhea was
      similar, albeit not statistically significant. CONCLUSIONS:  Our findings suggest
      an active role of H. pylori in protection against diarrheal diseases.

PMID- 22157172
TI  - Incidence of listeriosis and related mortality among groups at risk of acquiring
      listeriosis.
AB  - BACKGROUND: Listeriosis is a foodborne disease of significant public health
      concern that primarily affects persons with recognized underlying conditions or
      diseases that impair cell-mediated immunity. The degree of risk posed by the
      different underlying conditions is crucial to prioritize prevention programs that
      target the highest risk populations. METHODS: We reviewed cases of listeriosis
      reported in France from 2001 to 2008. Numbers of cases and deaths were tabulated
      by age and underlying condition. Measures of the impact of specific underlying
      conditions on the occurrence of listeriosis were calculated. For estimating the
      total number of persons living with specific diseases, we applied prevalence
      estimates of these diseases to the French population. Underlying conditions were
      ranked by the degree to which they increased the risk of listeriosis. RESULTS:
      From 2001 to 2008, 1959 cases of listeriosis were reported in France (mean annual
      incidence 0.39 per 100,000 residents). Compared with persons <65 years with no
      underlying conditions, those with chronic lymphocytic leukemia had a >1000-fold
      increased risk of acquiring listeriosis, and those with liver cancer;
      myeoloproliferative disorder; multiple myeloma; acute leukemia; giant cell
      arteritis; dialysis; esophageal, stomach, pancreas, lung, and brain cancer;
      cirrhosis; organ transplantation; and pregnancy had a 100-1000-fold increased
      risk of listeriosis. CONCLUSIONS: To be effective and acceptable to physicians
      and patients, listeriosis prevention strategies should be targeted based on
      evidence of increased risk. Stringent dietary guidance, to avoid specific foods
      with a high risk for Listeria contamination, should be targeted to pregnant women
      and to others at highest risk of listeriosis.

PMID- 22157173
TI  - Efficacy of imipenem for the treatment of bacteremia due to an OXA-48-producing
      Klebsiella pneumoniae isolate.

PMID- 22157174
TI  - HIV-1 dual infection is associated with faster CD4+ T-cell decline in a cohort of
      men with primary HIV infection.
AB  - BACKGROUND:  In vitro, animal, and mathematical models suggest that human
      immunodeficiency virus (HIV) co- or superinfection would result in increased
      fitness of the pathogen and, possibly, increased virulence. However, in patients,
      the impact of dual HIV type 1 (HIV-1) infection on disease progression is
      unclear, because parameters relevant for disease progression have not been
      strictly analyzed. The objective of the present study is to analyze the effect of
      dual HIV-1 infections on disease progression in a well-defined cohort of men who
      have sex with men. METHODS:  Between 2000 and 2009, 37 men who had primary
      infection with HIV-1 subtype B, no indication for immediate need of combination
      antiretroviral therapy (cART), and sufficient follow-up were characterized with
      regard to dual infection or single infection and to coreceptor use. Patients were
      followed to estimate the effect of these parameters on clinical disease
      progression, as defined by the rate of CD4(+) T-cell decline and the time to
      initiation of cART. RESULTS:  Four patients presented with HIV-1 coinfection; 6
      patients acquired HIV-1 superinfection, on average 8.5 months from their primary
      infection; and 27 patients remained infected with a single strain. Slopes of
      longitudinal CD4(+) T-cell counts and time-weighted changes from baseline were
      significantly steeper for patients with dual infection compared with patients
      with single infection. Multivariate analysis showed that the most important
      parameter associated with CD4(+) T-cell decline over time was dual infection (P =
      .001). Additionally, patients with HIV-1 coinfection had a significantly earlier
      start of cART (P < .0001). CONCLUSIONS:  Dual HIV-1 infection is the main factor
      associated with CD4(+) T-cell decline in men who have untreated primary infection
      with HIV-1 subtype B.

PMID- 22157175
TI  - The influence of antiretroviral therapy on the QTc interval in an African cohort.

PMID- 22157176
TI  - Non-Delta9tetrahydrocannabinol phytocannabinoids stimulate feeding in rats.
AB  - Cannabinoid type 1 receptor-mediated appetite stimulation by
      Delta9tetrahydrocannabinol (Delta9THC) is well understood. Recently, it has
      become apparent that non-Delta9THC phytocannabinoids could also alter feeding
      patterns. Here, we show definitively that non-Delta9THC phytocannabinoids
      stimulate feeding. Twelve male, Lister-Hooded rats were prefed to satiety prior
      to administration of a standardized cannabis extract or to either of two mixtures
      of pure phytocannabinoids (extract analogues) comprising the phytocannabinoids
      present in the same proportions as the standardized extract (one with and one
      without Delta9THC). Hourly intake and meal pattern data were recorded and
      analysed using two-way analysis of variance followed by one-way analysis of
      variance and Bonferroni post-hoc tests. Administration of both extract analogues
      significantly increased feeding behaviours over the period of the test. All three
      agents increased hour-one intake and meal-one size and decreased the latency to
      feed, although the zero-Delta9THC extract analogue did so to a lesser degree than
      the high-Delta9THC analogue. Furthermore, only the analogue containing Delta9THC
      significantly increased meal duration. The data confirm that at least one non
      Delta9THC phytocannabinoid induces feeding pattern changes in rats, although
      further trials using individual phytocannabinoids are required to fully
      understand the observed effects.

PMID- 22157177
TI  - Comparison of nafadotride, CNQX, and haloperidol on acquisition versus expression
      of amphetamine-conditioned place preference in rats.
AB  - Neurotransmission at dopamine (DA) and glutamate synapses has been implicated in
      conditioning place preference (CPP) in rats, but different receptor subtypes may
      be differentially involved in acquisition and expression. A balanced CPP was used
      to study the role of DA D2 and D3 and glutamatergic alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors in acquisition and
      expression of amphetamine (2.0 mg/kg) CPP. We tested the DA D3 receptor
      preferring antagonist nafadotride, the AMPA/kainate glutamate-receptor antagonist
      6-cyano-7-nitroquinoxaline-2,3-dione disodium salt (CNQX), and the DA D2 receptor
      preferring antagonist haloperidol. The results revealed that nafadotride (0.5
      mg/kg) and CNQX (0.05 mg/kg) blocked the expression of amphetamine CPP at a dose
      that failed to block acquisition. In contrast, haloperidol (0.1 mg/kg) blocked
      the acquisition of CPP at a dose that failed to block expression. Cotreatment
      with subthreshold doses of nafadotride (0.1 mg/kg) and CNQX (0.01 mg/kg) before
      the test session failed to block the expression of CPP. The results suggest that
      AMPA/kainate and DA D3 receptors are more strongly involved in the expression of
      amphetamine CPP and D2 receptors are more strongly involved in the acquisition of
      amphetamine CPP.

PMID- 22157178
TI  - Palliative care in emergency departments:  an impossible challenge?
AB  - The aim of this study was to investigate the care practices surrounding end-of
      life patients and the scope for providing palliative care in two emergency
      department short-stay units. Two qualitative methods of investigation were used:
      direct ethnographic-type observation and semi-directed group interviews. The
      results highlight the fact that end-of-life situations inflect the practices of
      care and give rise to adjustments in the organization of work. These practices
      operate in two registers: that of supporting the family and that of attention to
      the patient's comfort. We propose a typology of end-of-life patients. In
      conclusion, the practices, termed 'palliative care' by the caregivers, are
      addressed to terminally ill patients expected to die shortly. This issue should
      be debated within emergency departments.

PMID- 22157179
TI  - Inflammatory markers in heart failure: hype or hope?
AB  - Heart failure is a growing global epidemic that involves in its pathophysiology a
      proinflammatory state. Since the first description of elevated cytokine levels in
      this setting, there has been increasing interest in understanding the role of
      these molecules in left-ventricular remodeling and function. Over the years,
      intense research on the 'cytokine theory' of heart failure has allowed evaluation
      of the role of inflammatory biomarkers not only as pathogenetic mediators, but
      also as potential tools in the diagnosis and risk stratification of heart failure
      patients. Whereas current evidence does not support the use of inflammatory
      biomarkers for the diagnosis of heart failure, the assessment of their levels and
      the connection between their changes and changes in clinical status and prognosis
      has been well validated. At present, the utility of anti-inflammatory therapies
      in heart failure is still debated, since trials of anti-inflammatory agents in
      this setting have pointed out controversial results. On the contrary, established
      treatments of heart failure, including beta-blockers, renin-angiotensin system
      antagonists, and aldosterone-receptor blockers seem able to act by modulating
      cytokine expression, suggesting a new role for these molecules in guiding heart
      failure therapy. Therefore, the binomial topic of heart failure and inflammation
      still has a number of fields not completely explored: our aim is to update
      current knowledge and future perspectives. 

PMID- 22157180
TI  - Improved survival in patients with chronic mild/moderate systolic heart failure
      followed up in a specialist clinic.
AB  - OBJECTIVE: To relate therapeutic issues, comorbidities and functional parameters
      to mortality/morbidity of mild/moderate heart failure patients. METHODS: From our
      heart failure clinic, 372 heart failure patients (269 men, aged 66 +/- 11 years),
      with stable heart failure and ejection fraction 45% or less were recruited.
      Survival curves were estimated according to the Kaplan-Meier method. Associations
      of protective/risk factors with cardiovascular mortality/morbidity were also
      evaluated. RESULTS: One hundred and two patients (27%) died (aged 70 +/- 10 years
      at diagnosis, 76 +/- 10 at death) during follow-up (overall mortality at 60
      months: 19.2%; mean follow-up period: 67 +/- 44 months). Cardiovascular deaths
      were 64 (63% of total deaths, 44 men, age at diagnosis 70 +/- 9). Cardiovascular
      mortality at 60 months was 12%; standardized mortality ratio was 5.9 for women
      and 6.8 for men. The remaining 38 patients (37% of total deaths, 30 men, age at
      diagnosis 70 +/- 10) died of noncardiovascular causes. Overall, noncardiovascular
      mortality at 60 months was 7.2%; mean survival time from diagnosis to death was
      63 +/- 69 months (median 42, Q1 = 27.5, Q3 = 77.7). Average cardiovascular
      admission rate was 1.63 +/- 1.84 admissions/patient. At multivariate analysis,
      only previous history of myocardial infarction [hazard ratio: 3.62 (1.70-7.73)],
      class of ejection fraction at diagnosis [hazard ratio: 0.36 (0.32-0.60)], acute
      cardiac decompensation at any time [hazard ratio: 1.55 (1.32-1.84)], implanted
      defibrillator [hazard ratio: 0.11 (0.01-0.83)] and use of statins [hazard ratio:
      0.08 (0.007-0.42)] were independently associated with cardiovascular mortality.
      Factors associated to higher annual cardiovascular morbidity were age at
      diagnosis, chronic renal failure, diabetes, cardiac decompensation at any time,
      female sex and diuretic therapy. Angiotensin-converting enzyme (ACE) inhibitors
      and/or angiotensin-receptor-blockers reduced annual cardiovascular morbidity.
      CONCLUSION: Survival in mild/moderate heart failure patients has consistently
      improved. Further improvements are warranted in terms of morbidity reduction.

PMID- 22157181
TI  - Lack of definite indication criteria for choosing between transcatheter
      implantation and surgical replacement of the aortic valve.
AB  - AIMS: Age over 75 years and logistic Euroscore over 20% have been jointly
      proposed by European scientific associations as the criteria for aortic valve
      stenosis patients to be considered 'high-risk' for surgical aortic valve
      replacement (AVR) and candidates for transcatheter aortic valve implantation
      (TAVI). We aimed to verify traditional AVR outcomes in the presence of the above
      criteria. METHODS: Between January 2001 and January 2011, 180 patients with
      severe aortic valve stenosis (mean aortic valve area = 0.4+/-0.1 cm/m), with age
      range 75-88 years (mean 78.2+/-3), logistic Euroscore between 4.5 and 40% (mean
      12.6+/-7.4%), underwent surgical AVR. The patient population was divided into
      group A (118 patients between 75 and 79 years of age), further divided into
      subgroups A1 (76 patients) and A2 (42 patients) with logistic Euroscore,
      respectively, less than 20% and at least 20%; and group B (62 patients between 80
      and 88 years of age), subdivided into B1 (34 patients) and B2 (28 patients) with
      logistic Euroscore, respectively, less than 20% and at least 20%. Hospital
      outcomes were retrospectively evaluated. Univariate and multivariate analyses,
      including age and logistic Euroscore, were performed to individuate predictors of
      hospital mortality. RESULTS: Overall observed/expected mortality ratio was 0.4.
      Hospital mortality was 5.3% in group A1, 4.8% in A2, 5.9% in B1, 3.6% in B2
      (P=NS). Mortality with age over 75 and Euroscore at least 20% was 4.3%. As
      regards postoperative morbidity, atrio-ventricular bock indicating pacemaker
      implantation occurred in four patients, pneumonia in three, stroke in two,
      perioperative myocardial infarction in one. Age and Euroscore were not
      independent predictors of mortality, morbidity or composite endpoint in
      multivariable analysis. CONCLUSION: Age and logistic Euroscore might be
      inadequate criteria for the identification of patients with severe aortic
      stenosis unsuitable for AVR and addressable to TAVI.

PMID- 22157182
TI  - Orphan technology: unfunded early-stage bioscience is dropped off at the
      firehouse.

PMID- 22157183
TI  - The secret lives of stem cells: unraveling the molecular basis of stem cell
      aging.

PMID- 22157184
TI  - Computational approaches for the transcriptomics, proteomics and epigenetic
      analysis in adult stem cells.

PMID- 22157185
TI  - Biosprays: from the biomedical to the clinical sciences.

PMID- 22157186
TI  - Global profiling and relative quantifiction of histones, histone PTMs and histone
      modifying enzymes in mesenchymal stem cells using LC-MS/MS and a novel
      PerfectPair mass difference algorithm.

PMID- 22157187
TI  - Prospects and challenges for the use of stem cell technologies to develop novel
      therapies for Parkinson disease.

PMID- 22157188
TI  - The Buck Institute: an inside look.

PMID- 22157189
TI  - Adult stem cells: simply a tool for regenerative medicine or an additional piece
      in the puzzle of human aging?
AB  - Adult stem cells have taken center stage in current research related to
      regenerative medicine and pharmacogenomic studies seeking new therapeutic
      interventions. As we learn more about these cells, it is becoming apparent that
      the next big leap in our understanding of adult stem cell biology and adult stem
      cell aging will depend on the integration of approaches from various disciplines.
      Major advances and technological breakthroughs at the crossroad of fields such as
      biomaterials, genomics, epigenomics, and proteomics will enable the design of
      better tools to model human diseases, and warrant safe usage of adult stem cells
      in the clinic.

PMID- 22157190
TI  - Rapamycin-induced glucose intolerance: hunger or starvation diabetes.
AB  - Rapamycin prolongs healthy lifespan in yeast, flies and mammals and delays age
      related diseases, including cancer and atherosclerosis. Rapamycin is considered
      for prevention of diabetic complications, such as retinopathy and nephropathy,
      and acute treatment with rapamycin decreases insulin resistance. However, under
      certain conditions, chronic administration of rapamycin may cause glucose
      intolerance and even provoke type II diabetes. This does not fit logically with
      its potential effects against diabetic complications. This also seems puzzling,
      because calorie restriction (CR) can prevent type II diabetes and its
      complications, and rapamycin mimics CR. It was somehow forgotten that almost two
      centuries ago, Claude Bernard discovered "starvation diabetes," as shown later,
      characterized by glucose intolerance, decreased insulin, increased lipoproteins
      and ketones, gluconeogenesis and hepatic resistance to insulin. This reversible
      condition is not true diabetes: it does not lead to diabetic complications, and
      CR extends healthy lifespan. If rapamycin is a CR-mimetic, no wonder it may, in
      certain models, induce "hunger diabetes." But will rapamycin prevent true type II
      diabetes? Here are some answers.

PMID- 22157191
TI  - Bronchial asthma.
AB  - PURPOSE OF REVIEW: The aim of this review is to underline the need for an
      adequate clinical and functional evaluation of respiratory function and asthma
      control in patients undergoing surgical procedures requiring general anesthesia
      to obtain useful information for an adequate preoperative pharmacological
      approach. RECENT FINDINGS: It has been shown that baseline uncontrolled
      clinical/functional conditions of airways represent the most important risk
      factors for perioperative bronchospasm. In nonemergency conditions, asthma
      patients should undergo clinical/functional assessment at least 1 week before the
      surgery intervention to obtain, the better feasible control of asthma symptoms in
      the single patient. Some simple preoperative information given by the patient in
      preoperative consultation may be sufficient to identify individuals with
      uncontrolled or poor controlled asthmatic conditions. Spirometric evaluation is
      essential in individuals with poor control of symptoms, as well as in those
      patients with uncertain anamnestic data or limited perception of respiratory
      symptoms, and in those requiring lung resection. SUMMARY: A better control of
      asthma must be considered the 'gold standard' for a patient at 'a reasonable low
      risk' to develop perioperative/postoperative bronchospasm. International
      consensus promoted by pulmonologists, anesthesiologists, and allergists might be
      useful to define a better diagnostic and therapeutic approach.

PMID- 22157192
TI  - Management of fluid balance:  a European perspective.
AB  - PURPOSE OF REVIEW: Managing fluid balance mandates a clear identification of what
      goals are being sought at a particular point in the patient's pathway, an
      accurate assessment of both filling status and the degree of tissue hypoperfusion
      (if present), and a precise evaluation of response. RECENT FINDINGS: As no
      definitive data exist to show how the above targets should be optimally achieved,
      and with what fluid, many opinions of varied veracity currently exist. A
      perception from recent surveys is that critical care and intraoperative patients
      in Europe are more likely to receive synthetic colloid as the primary
      resuscitation fluid and to have cardiac output monitored by noninvasive or
      minimally invasive monitoring techniques. However, these preferences are based
      largely on tradition and local technology developments, albeit with an increasing
      evidence base for high-risk surgery. There is an increasing consensus that excess
      fluid should be avoided and that, after the initial resuscitation phase, efforts
      should be made to keep the patient in neutral (or perhaps negative) balance,
      unless clinically indicated. Likewise, the intravascular compartment should not
      remain underfilled if tissue hypoperfusion exists, acknowledging the above
      difficulties in agreeing upon definition and diagnosis. SUMMARY: Achieving and
      maintaining optimal fluid balance remains a significant challenge; better
      monitoring tools and definitive studies are needed.

PMID- 22157193
TI  - Patient blood management:  from blood-sparing techniques to the rationale use of
      blood products.

PMID- 22157194
TI  - High-frequency oscillatory ventilation in adults with acute respiratory distress
      syndrome.
AB  - PURPOSE OF REVIEW: High-frequency oscillatory ventilation (HFOV) is an attractive
      alternative to conventional lung protective ventilation. Adequate gas exchange is
      achieved with very small tidal volumes cycling at a high mean airway pressure.
      This may prevent injury from inspiratory overdistention and expiratory alveolar
      collapse. Most patients demonstrate improvements in oxygenation on HFOV though
      reductions in mortality are lacking. This may be explained by suboptimal
      technique. In this Opinion, the clinical experience using HFOV in adults in acute
      respiratory distress syndrome and the evolution of this ventilator technique are
      reviewed. RECENT FINDINGS: At some settings, currently available high-frequency
      ventilators may deliver tidal volumes that approach the magnitude of those
      delivered during conventional ventilation. Significantly smaller tidal volumes
      are achieved at higher frequencies (>6  Hz) and are tolerated in most patients.
      The aggressive use of recruitment maneuvers can significantly improve oxygenation
      during HFOV. Two large randomized controlled trials are underway that incorporate
      these findings into their protocols. However, not all patients tolerate HFOV and
      increased rates of barotrauma have been reported in some studies. SUMMARY:
      Although HFOV is theoretically appealing and may improve outcomes in adults with
      acute respiratory distress syndrome, it should be reserved for patients failing
      conventional ventilation until definitive trials are completed.

PMID- 22157195
TI  - Strategies to preempt and reduce the use of blood products:  an Australian
      perspective.
AB  - PURPOSE OF REVIEW: Evidence-based patient blood management (PBM) is aimed at
      achieving better patient outcomes by relying on a patient's own blood rather than
      on donor blood. This review covers the rationale behind PBM, the treatment
      modalities involved and the drivers to adopt PBM as a new standard of care.
      RECENT FINDINGS: Transfusion rates vary significantly between comparable
      countries; they also vary between centers for matched patients in standardized
      elective surgical interventions. Preoperative anemia, perioperative blood loss
      and liberal transfusion triggers are the main predictors for transfusion and pose
      risks to the patient. PBM is mitigating these risks by optimizing the patient's
      native red cell mass, minimizing blood loss, optimizing the physiological reserve
      of anemia and preempting transfusions. A growing number of studies show that
      transfusion is associated in a dose-dependent relationship with increased
      morbidity, mortality and hospital length of stay. Evidence suggests that this
      relationship is not merely associative but causal. Furthermore, the over-ageing
      population of the developed world leads to a growing gap between supply and
      demand of blood, the safety of donor blood remains unpredictable and the cost of
      transfusion is much higher than previously estimated. SUMMARY: High transfusion
      variability, adverse transfusion outcomes, limited evidence for the benefit of
      transfusion particularly in elective patients and high cost of transfusion are
      challenging the traditional transfusion paradigm. National and state-wide
      initiatives are underway in Australia to broadly implement PBM and PBM programs
      as a new and cost-effective standard of care in the public health system.

PMID- 22157196
TI  - Managing clotting:  a North American perspective.
AB  - PURPOSE OF REVIEW: Bleeding in a perioperative setting occurs due to multiple
      causes, but newer anticoagulant and antiplatelet therapies are increasingly used
      preoperatively. As a result, patients often can present for surgery with
      underlying hemostatic disorders due to these acquired disorders or following
      major surgery or trauma. Because bleeding occurs due to multiple causes, the
      addition of pharmacologic agents creates an acquired defect that complicates the
      surgical injury and may result in increased blood loss. An understanding of
      hemostasis and therapeutic approaches, especially those in our current clinical
      settings, is crucial in managing these patients. RECENT FINDINGS: Pharmacologic
      agents including antifibrinolytics and prohemostatic proteins are commonly
      administered, but a multimodal approach to management is important. Of note is
      that aprotinin has been reintroduced into the Canadian market in September 2011.
      Recombinant and purified coagulation therapies are under investigation, and
      provide clinicians specific agents to treat targeted deficiencies. SUMMARY:
      Nonsurgical bleeding in the operating room is the result of a multitude of
      factors including preoperative anticoagulants, dilution, fibrinolysis, and factor
      consumption. Therapeutic prohemostatic pharmacologic approaches, in addition to
      standard transfusion therapy, need to be considered in the prevention and
      treatment of coagulopathy in surgical patients.

PMID- 22157197
TI  - Management of the clotting system:  a European perspective.
AB  - PURPOSE OF REVIEW: Coagulation management remains a challenge for
      anesthesiologists involved in cardiovascular surgery as the population undergoing
      surgery becomes older and presents with more comorbidities. These patients are
      frequently treated with one or more agents that directly affect coagulation. This
      review will discuss what is known and the treatments available to manage
      coagulation in the perioperative setting of cardiac surgery. RECENT FINDINGS: New
      antithrombotics will be discussed as well as their proposed substitution in the
      preoperative period. The review will also describe the different products
      available in Europe for the treatment of bleeding and coagulopathy. Finally, the
      use of new monitoring devices will be discussed. SUMMARY: The introduction of new
      drugs with different mechanisms of action adds to the complexity of coagulation
      management during cardiovascular surgery. Monitoring needs to be developed and
      improved, especially for evaluating platelet function.

PMID- 22157198
TI  - Preoperative optimization:  rationale and process:  is it economic sense?
AB  - PURPOSE OF REVIEW: The development of preoperative clinics and the increasing
      importance of the anaesthetist in the management of surgical risk have expanded
      the concept of preoperative optimization. This review will focus on the rationale
      and process for cost-effective preoperative optimization. RECENT FINDINGS:
      Postoperative morbidity, rather than mortality, is the most important surgical
      outcome in economic terms. Since preoperative comorbidity, in association with
      surgical complexity, is more predictive of hospital costs than the subsequent
      treatment of postoperative complications per se, preoperative optimization
      represents an appropriate economic target. Process management, including
      guidelines to reduce unnecessary investigations and specialist referrals and
      enhancing perioperative recovery, makes economical sense in the majority of
      patients who undergo noncardiac surgery with few complications. Preoperative
      optimization of a minority of high-risk surgical patients is also important given
      limited critical care resource. However, the evidence for specific optimization
      strategies in this latter group continues to evolve and requires further
      clarification in well designed trials. SUMMARY: The requirement for appropriate
      methods of risk stratification of surgical patients targeted at the reduction of
      postoperative morbidity, underpins the development of cost-effective preoperative
      optimization. Specific process-based and clinical measures may then be applied to
      the development of individualized perioperative care packages.

PMID- 22157199
TI  - Costs and wastes in anesthesia care.
AB  - PURPOSE OF REVIEW: The current economic climate has put pressure on healthcare
      systems and providers, including anesthesiologists, to minimize costs without
      sacrificing patient safety. In this review, we discuss costs associated with
      anesthesia care, including medications and intraoperative monitoring, and suggest
      ways to reduce wastes and overall expenditure. RECENT FINDINGS: Significant
      amount, perhaps 20-50%, of drugs drawn up are never used but discarded as whole
      ampoules or vials. There has been a progressive shift to using more expensive
      inhalational agents and total intravenous anesthesia in the last 10 years.
      Highest drug costs are associated with total intravenous anesthesia protocols,
      which are five to 10 times more expensive than administering sevoflurane or
      desflurane with premedication using antiemetics. Among the inhalational agents,
      usage costs of sevoflurane and desflurane are 10 and 25 times, respectively, that
      of isoflurane. Bispectral index monitoring, which requires use of an expensive
      proprietary electrode is no better, perhaps even less effective, than titration
      of inhalational agents using end tidal anesthetic concentration to monitor depth
      of anesthesia and prevent intraoperative awareness. SUMMARY: Anesthesia
      medications comprise a significant proportion of hospital pharmacy budgets.
      Average anesthesia-related cost reductions of US$ 13-30 per cases multiplied by
      25 million anesthetics administered annually in the USA has the potential to
      yield savings of US$ 350-750 million. Bispectral index monitoring during
      inhalational anesthesia adds to the cost without providing any benefit.

PMID- 22157200
TI  - Is sugammadex economically viable for routine use.
AB  - PURPOSE OF REVIEW: Sugammadex belongs to a new class of drugs termed selective
      relaxant binding agents and is now available for clinical use in over 50
      countries. Because of its innovative mechanism of action, reversal of rocuronium
      or vecuronium becomes independent of the degree of residual neuromuscular
      blockade. Deep or intense neuromuscular blockade now can rapidly and predictably
      be reversed. However, compared with the classical acetylcholine esterase
      inhibitor-based reversal treatment costs are significantly higher. On the basis
      of the current literature, the cost-effectiveness of sugammadex will be
      evaluated. RECENT FINDINGS: There is a paucity of evidence-based studies that
      investigate the pharmacoeconomic aspects of sugammadex reversal. However, several
      studies assessed the cost-effectiveness of routine reversal with sugammadex
      compared with cholinesterase inhibitors and one study from the UK analyzed the
      economic aspects of a rocuronium/sugammadex concept compared with succinylcholine
      in a 'cannot intubate-cannot ventilate' scenario. The concept of cost reduction
      by dose reduction of sugammadex is also addressed. SUMMARY: The reduction of
      recovery times with sugammadex will reduce the incidence of prolonged extubation
      and may increase patients' throughput. However, the achievable reduction of costs
      depends on the individual organizational factors, also.

PMID- 22157201
TI  - Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial
      chemoembolization and RF ablation versus RF ablation alone: a prospective
      randomized trial.
AB  - PURPOSE: To compare prospectively the effects of radiofrequency (RF) ablation
      after transcatheter arterial chemoembolization (TACE) with those of RF ablation
      alone in the treatment of recurrent hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: This study was approved by the institutional ethics committee, and all
      patients gave written informed consent. From January 2002 to December 2006, 139
      patients with recurrent HCC measuring 5 cm in diameter or smaller were randomized
      to receive either sequential TACE and RF ablation (sequential treatment group,
      n=69) or RF ablation alone (RF ablation group, n=70). The survival curves were
      constructed with the Kaplan-Meier method and compared by using the log-rank test.
      Bonferroni correction was applied when multiple comparisons were performed.
      P<.0083 (.05/6) was considered indicative of a statistically significant
      difference. RESULTS: The 1-, 3-, and 5-year overall survival rates were 94%, 69%,
      and 46%, respectively, for the sequential treatment group and 82%, 47%, and 36%
      for the RF ablation group (P=.037). The corresponding recurrence-free survival
      rates were 80%, 45%, and 40% for the sequential treatment group and 64%, 18%, and
      18% for the ablation group (P=.005). At subgroup analyses, the overall survival
      for the sequential treatment group was better than that for the RF ablation group
      for patients with tumor recurrence 1 year or less after initial treatment
      (P=.004) and those with tumors measuring 3.1-5.0 cm (P=.002) but not for those
      with tumor recurrence more than 1 year after initial treatment (P=.421) and those
      with tumors 3.0 cm or smaller (P=.478). The recurrence-free survival in the
      sequential treatment group was better than that in the RF ablation group for
      patients with tumors measuring 3.1-5.0 cm (P<.001) but not for those with tumors
      3.0 cm or smaller (P=.204). For recurrence-free survival, there was no
      significant difference between the two groups for patients with tumor recurrence
      1 year or less or more than 1 year after initial treatment (P=.020 and P=.111,
      respectively). Logistic regression analysis showed that treatment allocation and
      the interval between initial treatment and tumor recurrence were significant
      prognostic factors for overall survival, whereas the interval between initial
      treatment and tumor recurrence, treatment allocation, and tumor size were
      significant prognostic factors for recurrence-free survival. CONCLUSION: The
      efficacy of sequential TACE-RF ablation is better than that of RF ablation alone
      for recurrent HCC.

PMID- 22157202
TI  - Differentiation of normal thymus from anterior mediastinal lymphoma and lymphoma
      recurrence at pediatric PET/CT.
AB  - PURPOSE: To evaluate the role of positron emission tomography (PET)/computed
      tomography (CT) in the differentiation of normal thymus from mediastinal lymphoma
      and lymphoma recurrence in pediatric patients. MATERIALS AND METHODS: The study
      was approved by the institutional review board, and informed consent was waived.
      The study was HIPAA compliant. Two hundred eighty-two fluorine 18
      fluorodeoxyglucose PET/CT studies in 75 pediatric oncology patients were reviewed
      retrospectively. Patients were divided into four groups: anterior mediastinal
      lymphoma (group A, n=16), anterior mediastinal lymphoma with subsequent
      recurrence (group B, n=5), lymphoma outside the mediastinum (group C, n=16), and
      other malignant tumors outside the thymus (group D, n=38). Analyses included
      measurements of the maximum anteroposterior and transverse dimensions of the
      anterior mediastinal mass or thymus on axial CT images and measurements of
      maximum standardized uptake values of anterior mediastinal mass, thymus (SUVt),
      and bone marrow at the level of the fifth lumbar vertebra (SUVb) on PET images.
      Quantitative parameters were compared by using an analysis of variance test.
      RESULTS: Mean prechemotherapy SUVt was 4.82 for group A, 8.45 for group B, 2.00
      for group C, and 2.09 for group D. Mean postchemotherapy SUVt for group B was
      4.74. Thymic rebound (mean SUVt, 2.89) was seen in 44% of patients at a mean
      interval of 10 months from the end of chemotherapy. The differences between
      prechemotherapy SUVt of mediastinal lymphoma and normal thymus and
      postchemotherapy SUVt of lymphoma recurrence and thymic rebound were highly
      significant (P<.001). CONCLUSION: SUVt is a sensitive predictor for
      differentiation of normal thymus or thymic rebound from mediastinal lymphoma.
      SUVt of 3.4 or higher is a strong predictor of mediastinal lymphoma.

PMID- 22157203
TI  - Ileal Crohn disease: mural microvascularity quantified with contrast-enhanced US
      correlates with disease activity.
AB  - PURPOSE: To quantitatively assess microvascular activation in the thickened ileal
      walls of patients with Crohn disease (CD) by using contrast-enhanced
      ultrasonography (US) and evaluate its correlation with widely used indexes of CD
      activity. MATERIALS AND METHODS: This prospective study was approved by the
      ethics committee, and written informed consent was obtained from all patients.
      The authors examined 54 consecutively enrolled patients (mean age, 35.29 years;
      age range, 18-69 years; 39 men, 15 women) with endoscopically confirmed CD of the
      terminal ileum. Ileal wall segments thicker than 3 mm were examined with low
      mechanical-index contrast-enhanced US and a second-generation US contrast agent.
      The authors analyzed software-plotted time-enhancement intensity curves to
      determine the maximum peak intensity (MPI) and wash-in slope coefficient (beta)
      and evaluated their correlation with (a) the composite index of CD activity
      (CICDA), (b) the CD activity index (CDAI), and (c) the simplified endoscopic
      score for CD (SES-CD, evaluated in 37 patients) for the terminal ileum.
      Statistical analysis was performed with the Mann-Whitney test, Spearman rank
      test, and receiver operating characteristic (ROC) analysis. RESULTS: MPI and beta
      coefficients were significantly increased in the 36 patients with a CICDA
      indicative of active disease (P<.0001 for both), the 33 patients with a CDAI of
      at least 150 (P<.032 and P<.0074, respectively), and the 26 patients with an SES
      CD of at least 1 (P<.0001 and P<.002, respectively). ROC analysis revealed
      accurate identification (compared with CICDA) of active CD with an MPI threshold
      of 24 video intensity (VI) (sensitivity, 97%; specificity, 83%) and a beta
      coefficient of 4.5 VI/sec (sensitivity, 86%; specificity, 83%). CONCLUSION:
      Contrast-enhanced US of the ileal wall is a promising method for objective,
      reproducible assessment of disease activity in patients with ileal CD.

PMID- 22157204
TI  - Iron deficiency anaemia:  a review of diagnosis, investigation and management.
AB  - Iron deficiency anaemia (IDA) is the most common form of anaemia worldwide. In
      men and postmenopausal women the commonest cause of IDA is blood loss from
      lesions in the gastrointestinal tract, making it a common cause of referral to
      gastroenterologists. Causes of IDA relate either to blood loss or iron
      malabsorption. After confirmation with laboratory tests, gastrointestinal
      evaluation is almost always indicated to exclude gastrointestinal malignancy.
      Specific patient groups such as premenopausal women, patients with low-normal
      ferritin and iron-deficient patients without anaemia may need an individualized
      approach. A small proportion of patients have recurrent or persistent IDA despite
      negative standard endoscopies. These patients with obscure gastrointestinal
      bleeding usually require evaluation of the small bowel with capsule endoscopy or
      double balloon enteroscopy. Treatment should involve prompt iron replacement plus
      diagnostic steps directed towards correcting the underlying cause of IDA. Oral
      iron replacement is cheap and effective, but parenteral (intravenous) therapy may
      be required due to intolerance, noncompliance or treatment failure with oral
      therapy.

PMID- 22157205
TI  - Validity of suicide statistics in Europe in relation to undetermined deaths:
      developing the 2-20 benchmark.
AB  - BACKGROUND: The suicide rate is a macro indicator of the population's
      psychosocial wellbeing and an evaluation criterion of the effectiveness of
      suicide prevention strategies. A high level of injury deaths of undetermined
      intent (UD) is usually discussed in connection with the validity of suicide
      statistics. An effort is made to develop a criterion to characterise the quality
      of suicide statistics. METHODS: Standardised rates of suicides (X60-X84) and UD
      (Y10-Y34) by the International Classification of Disease version 10 as an average
      for the past five available years were taken from the WHO European mortality
      database. Rate ratios were computed by dividing rates of UD by suicide rates.
      RESULTS: There is considerable variation in suicide and UD rates among countries.
      The highest overall rates of UD were registered in Russia, Ukraine and Belarus,
      and the lowest in Greece, Spain and Italy. The EU-15 average UD rate of 1.97 and
      the rate ratio of 0.194 UD to suicides were combined into a '2-20 benchmark', in
      which the primary indicator is 2.0 UD cases per 100,000 and the secondary
      indicator is the proportion of UD to suicides 0.20 (20%), which enables countries
      to be clustered according to the quality of suicide statistics. The following
      countries satisfied the benchmark: Greece, Norway, Spain, The Netherlands,
      Luxembourg, France, Austria, Italy, Romania, Hungary, Ireland and Finland.
      CONCLUSION: This study used the developed '2-20 benchmark' in Europe to assess
      suicide registration quality in a particular country, to compare the relative
      position of countries, and to set a target for those European countries that have
      not yet achieved the benchmark.

PMID- 22157206
TI  - The impact of pedestrian countdown signals on pedestrian-motor vehicle
      collisions: a quasi-experimental study.
AB  - OBJECTIVE: To determine whether pedestrian countdown signals (PCS) reduce
      pedestrian-motor vehicle collisions in the city of Toronto, Canada. METHODS: A
      quasi-experimental study design was used to evaluate the effect of PCS on the
      number of pedestrian-motor vehicle collisions in the city of Toronto, from
      January 2000 to December 2009. Each intersection acted as its own control. We
      compared the number of pedestrian-motor vehicle collisions per intersection-month
      before and after the intervention. Stratified models were used to evaluate effect
      modification by pedestrian age, injury severity and location (urban vs inner
      suburbs). Poisson regression analysis with repeated measures (generalised
      estimating equations) was used to estimate the RR and 95% CI. RESULTS: The
      analysis included 9262 pedestrian-motor vehicle collisions at 1965 intersections.
      The RR of collisions after PCS installation was 1.014 (95% CI 0.958 to 1.073),
      indicating no statistically significant effect of PCS on collisions. There was no
      evidence to suggest effect modification between PCS and collisions by age, injury
      severity or location. CONCLUSION: The installation of PCS at 1965 signalised
      intersections in Toronto did not reduce the number of pedestrian-motor vehicle
      collisions at these intersections.

PMID- 22157207
TI  - Building capacity of drivers in Nigeria to provide first aid for road crash
      victims.
AB  - This paper presents the effect of first aid training on the first aid knowledge
      and skills of university drivers. The intervention group (n=98) received training
      on first aid and controls (n=78) received training on HIV/AIDS. First aid
      knowledge and skills were measured at baseline, immediately after the training
      and 4 months post-intervention. Changes in knowledge and skills were assessed
      using repeated measures analysis of variance. Knowledge scores were 51.2+/-14.8%,
      59.6+/-12.8% and 57.6+/-12.8% (p>0.05) for intervention drivers versus 51.6+/
      11.6%, 53.2+/-12.0% and 56.4+/-12.4% (p>0.05) in controls. The skill scores for
      intervention drivers were 49.2+/-14.2%, 78.3+/-12.9% and 77.5+/-11.7% (p<0.05)
      versus 37.7+/-12.4%, 40.4+/-16.3% and 41.7+/-12.1% (p>0.05) for controls. Four
      months after intervention, >75% of the 13 intervention drivers who came across a
      crash had used the skills acquired. The intervention improved the first aid
      skills of intervention drivers. In view of the reduction in scores by the fourth
      month post-intervention, periodic refresher training is recommended to sustain
      the skills acquired.

PMID- 22157210
TI  - Current world literature.

PMID- 22157208
TI  - Estimated acute effects of ambient ozone and nitrogen dioxide on mortality in the
      Pearl River Delta of southern China.
AB  - BACKGROUND AND OBJECTIVES: Epidemiologic studies have attributed adverse health
      effects to air pollution; however, controversy remains regarding the relationship
      between ambient oxidants [ozone (O3) and nitrogen dioxide (NO2)] and mortality,
      especially in Asia. We conducted a four-city time-series study to investigate
      acute effects of O3 and NO2 in the Pearl River Delta (PRD) of southern China,
      using data from 2006 through 2008. METHODS: We used generalized linear models
      with Poisson regression incorporating natural spline functions to analyze acute
      mortality in association with O3 and NO2, with PM10 (particulate matter <= 10 MUm
      in diameter) included as a major confounder. Effect estimates were determined for
      individual cities and for the four cities as a whole. We stratified the analysis
      according to high- and low- exposure periods for O3. RESULTS: We found consistent
      positive associations between ambient oxidants and daily mortality across the PRD
      cities. Overall, 10-MUg/m3 increases in average O3 and NO2 concentrations over
      the previous 2 days were associated with 0.81% [95% confidence interval (CI):
      0.63%, 1.00%] and 1.95% (95% CI: 1.62%, 2.29%) increases in total mortality,
      respectively, with stronger estimated effects for cardiovascular and respiratory
      mortality. After adjusting for PM10, estimated effects of O3 on total and
      cardiovascular mortality were stronger for exposure during high-exposure months
      (September through November), whereas respiratory mortality was associated with
      O3 exposure during nonpeak exposure months only. CONCLUSIONS: Our findings
      suggest significant acute mortality effects of O3 and NO2 in the PRD and
      strengthen the rationale for further limiting the ambient pollution levels in the
      area.

PMID- 22157209
TI  - The effect of dietary guidelines on cancer risk and mortality.
AB  - PURPOSE OF REVIEW: Dietary guidelines are important tools for educating the
      general public and helping health professionals promote good health and prevent
      chronic diet-related diseases. However, it is of major public health relevance
      that the effect of the guidelines per se is evaluated to make sure that they
      serve their purpose. The aim of this article is to review the current research on
      dietary guidelines and their effect on cancer risk and mortality. RECENT
      FINDINGS: Since the last 30-40 years, most industrialized countries have had
      dietary guidelines. The guidelines are based on thorough reviews of the current
      scientific evidence regarding dietary intake and health. Potential health
      benefits associated with good adherence to the guidelines have been evaluated in
      observational studies during the last 15 years, with an increase in the number of
      studies during the most recent years. SUMMARY: Available data on the potential
      association between dietary guidelines and cancer are limited and inconclusive. A
      meta-analysis of studies on overall cancer risk shows no protective effect for
      good adherence to the dietary guidelines as compared with poor adherence.
      However, good adherence was associated with a 21% reduced risk of colorectal
      cancer, and 22% reduced cancer-specific mortality.

PMID- 22157212
TI  - Cancer of the orbit and adnexa.
AB  - The diagnosis and treatment of orbital and periorbital malignancies are
      challenging. These tumors can result in blindness, death, and significant
      cosmetic deformities. Herein, we present the most common ocular malignancies and
      a systematic approach to diagnosis. Further, we integrate the seventh edition
      American Joint Committee on Cancer staging system, biomarkers, and
      multidisciplinary approaches to treatment.

PMID- 22157213
TI  - Effect of anti-inflammatory (IL-4, IL-10) cytokine genes in relation to risk of
      cervical carcinoma.
AB  - OBJECTIVES: Cervical cancer is rated the second most common malignant tumor
      globally and is etiologically linked to human papillomavirus infection.
      Interleukin-4 (IL-4) and IL-10 are cytokines with anti-inflammatory properties.
      The purpose of this study was to determine the relationship of different alleles
      of IL-4 and IL-10 genes with risk of cervical cancer among passive smokers and
      users of oral contraceptives. MATERIALS AND METHODS: We investigated the
      association of cervical cancer with 2 anti-inflammatory cytokine genes IL-4 and
      IL-10 using a case-control study. The study sample comprised 200 cases of
      cervical cancer and an equal number of matched controls who were investisgated by
      variable number of tandem repeat and Restriction Fragment Length Polymorphism
      analysis. RESULTS: In this study we observed that the Rp1/Rp2 genotype of IL-4
      marginally increased the risk of developing cervical cancer [odds ratio (OR),
      1.3; 95% confidence intervals (CI), 0.45-3.64; P=0.8]. In case of passive smokers
      we also found a marginal increase in the risk for cervical cancer with AC and
      combined AC+CC genotypes (OR, 1.7; 95% CI, 0.90-3.34; P=0.1; and OR,1.7; 95% CI,
      0.90-3.17; P=0.1, respectively). However, a nonsignificant association was
      observed between use of oral contraceptives and risk of cervical cancer with anti
      inflammatory cytokine genotypes. CONCLUSIONS: This study suggests that passive
      smokers among North Indian women having IL-4 Rp1/Rp2 and IL-10 (AC) genotypes had
      an increased risk for developing cervical cancer.

PMID- 22157214
TI  - Impact of neoadjuvant chemotherapy on physical fitness, physical activity, and
      health-related quality of life of patients with resectable esophageal cancer.
AB  - OBJECTIVE: Neoadjuvant chemotherapy (NAC) followed by radical surgery is the
      standard treatment for patients with resectable esophageal squamous cell
      carcinoma (ESCC) in Japan. However, some adverse events associated with NAC may
      result in a decrease in physical fitness that may influence the patient's ability
      to tolerate surgery. The purpose of this study was to evaluate the impact of NAC
      on physical fitness, physical activity, and health-related quality of life
      (HRQOL) of patients with ESCC. METHODS: In this prospective study, we
      investigated 27 consecutive patients with newly diagnosed resectable ESCC who
      were scheduled to receive NAC followed by surgery between January 2009 and
      November 2010. Primary endpoints were change from baseline in physical fitness
      (knee extensor muscle strength and 6-min walking distance) and physical activity
      after NAC. A secondary endpoint was change from baseline in HRQOL. RESULTS:
      Physical fitness and physical activity level after NAC did not differ
      significantly from those before NAC. With regard to HRQOL, only social
      functioning was significantly different (P=0.04). The change in physical activity
      demonstrated a significant correlation with the change in 6-minute walking
      distance (r=0.45, P=0.02). CONCLUSIONS: NAC had no impact on physical fitness and
      physical activity in patients with ESCC. This result indicated that there was no
      need for a physiotherapy intervention during NAC to prevent a decline in these
      parameters.

PMID- 22157215
TI  - Comparison of lymphedema in patients with axillary lymph node dissections to
      those with sentinel lymph node biopsy followed by immediate and delayed ALND.
AB  - PURPOSE: The purpose of the study was to show that delayed axillary lymph node
      dissection (ALND) has higher rates of lymphedema compared with immediate ALND,
      using data from NSABP-B32 at Beaumont Hospital. METHOD: NSABP B-32 at Beaumont
      had 207 patients with follow-up data on 199 patients, randomizing clinically
      negative axilla to sentinel lymph node biopsy (SLNB)+ALND (GrA N=98), and
      SLNB+cytology+/-ALND (GrB N=101). All patients had preoperative volumetric arm
      measurements and only node negatives had routine postoperative measurements
      assessing lymphedema for 36 months. We contacted node-positive patients for
      postoperative measurements for this study. Twenty-four and 15 cytology-positive
      patients had SLNB+ALND in GrA and GrB, respectively (SubGrA1 N=24; SubGrB1 N=15).
      Fourteen hematoxylin and eosin-positive patients had delayed ALND (SubGrB2a
      N=14). RESULTS: Lymphedema rate for node-positive SLNB+ALND was 10.3% [SubGrA1
      (3/24)+SubGrB1 (1/15)=4/39] and node-negative SLNB+ALND was 6.8% (SubGrA2=5/74).
      Lymphedema was 14.3% for delayed ALND in SubGrB2a (2 of 14) and 0% for 72 SLNBs
      in SubGrB2b. Our study comparing immediate and delayed ALND lymphedema was not
      statistically significant (10.3% vs. 14.3%, P=0.65). Comparing node-negative ALND
      (SubGrA2= 5/74=6.8%) to node-positive ALND (A1+B1+B2a=6/53=11.3%) was not
      statistically significant (P=0.52). Comparing lymphedema for node-negative ALND
      (SubGrA2) to SLNB (SubGrB2b) only approached significance (6.8% vs. 0%, P=0.058).
      CONCLUSIONS: The rate of lymphedema was higher in delayed ALND but not
      statistically significant. Comparison, however, is difficult, given the limited
      sample size. We urge the other centers of NSABP-B32 to validate this, by
      contacting the node-positive patients for measurements. The lymphedema rate for
      SLNB alone was 0% and approached statistical significance when compared with node
      negative ALND.

PMID- 22157216
TI  - Phase II study of gemcitabine in combination with regional arterial infusion of
      nafamostat mesilate for advanced pancreatic cancer.
AB  - PURPOSE: To evaluate the efficacy of regional arterial infusion of the synthetic
      serine protease inhibitor nafamostat mesilate combined with gemcitabine for the
      treatment of patients with unresectable locally advanced or metastatic pancreatic
      cancer. MATERIALS AND METHODS: A single-arm, single center, institutional review
      board-approved phase II trial was conducted. Thirty-five of 38 consecutive
      patients were included in the study. Patients received nafamostat mesilate (4.8
      mg/kg continuous regional arterial infusion) with gemcitabine (1000 mg/m
      intravenously) on days 1, 8, and 15. This treatment was repeated at 28-day
      intervals. The primary endpoints were to evaluate overall survival and 1-year
      survival rate. The secondary endpoints were to assess therapeutic response and
      clinical benefit response. Overall survival times were estimated by the Kaplan
      Meier survival analysis. RESULTS: The median survival time was 10.0 months, and
      the 1-year survival rate was 40.0%. The response rate and disease control rate
      were 17.1% and 88.6%, respectively. A fraction of 25% of the patients who
      required opioids for cancer-related pain could reduce their opioid intake, and
      37.1% of the patients showed healthy weight gain. Among the patients with
      metastatic pancreatic cancer, the median survival time was 9.0 months, and the 1
      year survival rate was 32.0%. The proposed regimen offers an economic advantage
      compared with recent therapy regimens that have shown significant improvements in
      median survival over standard chemotherapy with gemcitabine. CONCLUSIONS: An
      alternative regimen for unresectable pancreatic cancer, especially for metastatic
      pancreatic cancer, is proposed based on acceptable survival time, clinical
      benefit, and cost advantage.

PMID- 22157217
TI  - Biography of David Fleischer, MD.

PMID- 22157218
TI  - Same day prep for afternoon colonoscopy: everybody wins!

PMID- 22157219
TI  - Multidetector CT for GI bleeding: first-line diagnostic study?

PMID- 22157220
TI  - Gastrointestinal and hepatic manifestations of Sjogren syndrome.
AB  - Sjogren syndrome (SS) is an autoimmune disease that affects exocrine glands and
      therefore may affect the gastrointestinal system, from the mouth, esophagus, and
      bowel to the liver and pancreas. Oral involvement in SS is mainly characterized
      by dryness, with a wide spectrum of symptoms, from mild-to-severe xerostomia with
      dysgeusia and tooth decay. The dysphagia, although common, does not correlate
      with the reduced salivary flow rate or the dysmotility that may be present.
      Dyspepsia, found in up to 23% of patients, may be associated with gastritis,
      reduced acid production, and antiparietal cell antibodies, but rarely pernicious
      anemia. Pancreatic involvement, although rare, includes pancreatitis and
      pancreatic insufficiency. The most common causes of liver disease are primary
      biliary cirrhosis, autoimmune hepatitis, nonalcoholic fatty liver disease, and
      hepatitis C virus (HCV). Although abnormal liver tests are found in up to 49% of
      patients, they are usually mild. Although sicca syndrome, abnormal histology of
      the salivary glands, and abnormal sialograms are common in primary biliary
      cirrhosis, the antibodies to Ro/SSA or La/SSB antigens are infrequent.
      Xerostomia, sialadenitis, abnormal salivary flow rates, and abnormal Schirmer
      test in HCV vary widely among the studies, although the antibodies to Ro/SSA or
      La/SSB are only 1%. Several studies show that HCV is in saliva, although how this
      may impact sicca syndrome or SS in HCV is unclear. SS as a disease of exocrine
      glands affects many parts of the gastrointestinal system.

PMID- 22157221
TI  - Utilization and outcomes of palliative therapy for hepatocellular carcinoma: a
      population-based study in the United States.
AB  - GOALS: To evaluate the utilization and determinants of receiving palliative
      treatment for hepatocellular carcinoma (HCC), and its effect on survival.
      BACKGROUND: Palliative treatment for HCC, including transarterial
      chemoembolization (TACE) and systemic chemotherapy, is available for patients who
      do not receive potentially curative therapy. The utilization and outcomes of
      these therapies in clinical practice are unknown. STUDY: We conducted a
      population-based cohort study using the Surveillance, Epidemiology, and End
      Results Registry data linked to Medicare claims of HCC patients aged above 65
      years diagnosed during 2000 to 2005 who did not receive liver transplant,
      resection, or ablation. The proportions of patients who received TACE or systemic
      chemotherapy were calculated by tumor stage, liver disease status, and non-HCC
      comorbidity. Determinants of receiving palliative therapy were examined in
      logistic regression models and propensity scores were calculated. Cox
      proportional hazards models were used to evaluate mortality risk. RESULTS: We
      identified 3163 HCC patients (median age, 75 y; 67% men) who did not receive
      potentially curative treatment. Approximately 12.5% of patients received TACE and
      11.0% received chemotherapy. In patients with early or intermediate stage HCC, no
      liver decompensation, and little or no comorbidity, only 22.8% received TACE and
      13.8% received chemotherapy. Median survival was significantly higher among
      patients who received TACE (14.0 mo) compared with who received chemotherapy (5.0
      mo) or no therapy (2.0 mo). A significant reduction in overall mortality was
      observed for TACE (54%) and chemotherapy (33%). CONCLUSIONS: Utilization of
      palliative treatment for HCC is low, which could not be explained by clinical
      features. However, misclassification could have occurred due to the data source.
      Receipt of TACE or systemic chemotherapy was associated with a reduction in
      mortality.

PMID- 22157222
TI  - Pathologic complete response after FOLFOX7 in a locally advanced rectal cancer.

PMID- 22157224
TI  - WGO Train the Trainers Workshop Porto Alegre, Brazil 2011.

PMID- 22157223
TI  - Impact of total fundoplication on esophageal transit: analysis by combined
      multichannel intraluminal impedance and manometry.
AB  - BACKGROUND: Laparoscopic total fundoplication is considered the most effective
      surgical option for gastroesophageal reflux (GER) disease. Some authors assume
      that total fundoplication may expose the patient to delayed transit of the
      swallowed bolus and increased risk of dysphagia, particularly when peristaltic
      dysfunction is present. We undertook this study to evaluate by means of combined
      multichannel intraluminal impedance and esophageal manometry (MII-EM) the impact
      of fundoplication on esophageal physiology. An objective measurement of the
      influence of the total wrap on bolus transit may be helpful in refining the
      optimal antireflux wrap (ie, partial vs. total). METHODS: In this study, 25
      consecutive patients who underwent laparoscopic Nissen-Rossetti fundoplication
      had MII-EM and combined 24-hour pH and multichannel intraluminal impedance (MII
      pH) before and after the surgical procedure. All patients completed preoperative
      and postoperative symptom questionnaires. The following were calculated for
      liquid and viscous deglutition lower esophageal sphincter pressure and
      relaxation, distal esophageal amplitude, the number of complete esophageal bolus
      transits and the mean total bolus transit time. The acid and nonacid GER episodes
      were calculated by MII-pH with the patient in both upright and recumbent
      positions. RESULTS: The postoperative MII-EM showed an increased lower esophageal
      sphincter pressure (P < 0.05), whereas lower esophageal sphincter relaxation and
      distal esophageal amplitude did not change after surgery (P = NS). Complete
      esophageal bolus transits and bolus transit time did not change for liquid
      swallows (P = NS), but was more rapid for viscous after surgery (P < 0.05).
      Twenty-four hour pH monitoring confirmed the postoperative reduction of both acid
      and nonacid reflux (P < 0.05). CONCLUSIONS: Laparoscopic Nissen-Rossetti is
      effective in controlling both acid and nonacid GER without impairment of
      esophageal function. Appropriate preoperative investigation, meticulous patient
      selection and correct surgical technique are extremely important in securing good
      results.

PMID- 22157225
TI  - Dominant-negative isoforms of Tcf/Lef proteins in development and disease.

PMID- 22157226
TI  - More on the pro-fertility activity of p53: the blastocyst side.

PMID- 22157227
TI  - Beyond tumor suppression: p53 controls blastocyst implantation.

PMID- 22157228
TI  - A conundrum in mammalian hematopoietic stem cell polarity.

PMID- 22157229
TI  - A randomized trial of computer-delivered brief intervention and low-intensity
      contingency management for smoking during pregnancy.
AB  - INTRODUCTION: Implementation of evidence-based interventions for smoking during
      pregnancy is challenging. We developed 2 highly replicable interventions for
      smoking during pregnancy: (a) a computer-delivered 5As-based brief intervention
      (CD-5As) and (b) a computer-assisted, simplified, and low-intensity contingency
      management (CM-Lite). METHODS: A sample of 110 primarily Black pregnant women
      reporting smoking in the past week were recruited from prenatal care clinics and
      randomly assigned to CD-5As (n = 26), CM-Lite (n = 28), CD-5As plus CM-Lite (n =
      30), or treatment as usual (n = 26). Self-report of smoking, urine cotinine, and
      breath CO were measured 10 weeks following randomization. RESULTS: Participants
      rated both interventions highly (e.g., 87.5% of CD-5As participants reported
      increases in likelihood of quitting), but most CM-Lite participants did not
      initiate reinforcement sessions and did not show increased abstinence. CD-5As led
      to increased abstinence as measured by cotinine (43.5% cotinine negative vs.
      17.4%; odds ratio [OR] = 10.1, p = .02) but not for CO-confirmed 7-day point
      prevalence (30.4% abstinent vs. 8.7%; OR = 5.7, p = .06). Collapsing across CM
      Lite status, participants receiving the CD-5As intervention were more likely to
      talk to a doctor or nurse about their smoking (60.5% vs. 30.8%; OR = 3.0, p =
      .02). CONCLUSIONS: Low-intensity participant-initiated CM did not affect smoking
      in this sample, but the CD-5As intervention was successful in increasing
      abstinence during pregnancy. Further research should seek to replicate these
      results in larger and more diverse samples. Should CD-5As continue to prove
      efficacious, it could greatly increase the proportion of pregnant smokers who
      receive an evidence-based brief intervention.

PMID- 22157231
TI  - Temporal stability of a cigarette purchase task.
AB  - INTRODUCTION: Cigarette purchase tasks (CPTs) are relatively new behavioral
      economic assessments that efficiently quantify motivation for tobacco by
      assessing how much an individual values cigarettes. This is achieved by assessing
      estimated cigarette consumption at escalating levels of price per cigarette and
      generating several measures of motivation from the resulting demand curve. The
      temporal stability of the indices generated from a CPT has not been examined to
      date and was the focus of the current study. METHODS: Participants were 11
      moderately heavy smokers from the community who completed CPTs and other measures
      on 2 occasions 1 week apart. The CPT indices of the relative value of cigarettes
      were (a) intensity (i.e., consumption under minimal cost), (b) O(max) (i.e.,
      maximum expenditure for cigarettes), (c) breakpoint (i.e., first price
      suppressing consumption to 0), and (d) elasticity (i.e., proportionate price
      sensitivity). RESULTS: Demand for cigarettes was initially insensitive to price
      changes (inelastic) but became increasingly sensitive (elastic) as prices
      increased. Correlations between the demand indices at both administrations were
      very high magnitude and statistically significant (rs = .76-.99, ps < .001), and
      no significant within-subjects differences were present. CONCLUSIONS: These
      findings provide initial support for the temporal stability of motivation for
      tobacco as measured by a CPT. Future studies with larger samples and timeframes
      will be important to verify these findings.

PMID- 22157230
TI  - Correlates of chilean adolescents' negative attitudes toward cigarettes: the role
      of gender, peer, parental, and environmental factors.
AB  - INTRODUCTION: We examined the association of peer, parental, and environmental
      factors with negative attitudes toward cigarettes among youth from Santiago,
      Chile. METHODS: A total of 860 youth from Santiago, Chile, completed questions
      regarding their lifetime use of cigarettes, intentions to smoke, attitudes toward
      cigarettes, and questions that assessed peer, parental, and environmental
      factors. RESULTS: For both boys and girls, peer disapproval of smoking was
      associated with more negative attitudes toward cigarettes and peer smoking was
      associated with less negative attitudes toward cigarettes. Peer pressure was
      significantly associated with more negative attitudes toward cigarettes for girls
      only. Parental smoking was associated with less negative attitudes and parental
      control with more negative attitudes, but these associations were significant in
      the overall sample only. School prevention efforts and exposure to cigarette ads
      were not associated with cigarette attitudes. Difficulty in accessing cigarettes
      was positively associated with negative attitudes for boys and girls. CONCLUSION:
      Smoking prevention efforts focus on attitude change, but scant information is
      available about the experiences that influence Chilean youth's attitudes toward
      cigarettes. Results from the current study suggest that prevention efforts could
      benefit from gender-specific strategies. Girls' but not boys' attitudes were
      influenced by peer pressure. Moreover, negative attitudes toward cigarettes were
      associated with lower current smoking in girls only. Parental smoking was an
      important influence on youth's attitudes toward cigarettes. Efforts to reduce
      smoking among Chilean youth may benefit from concurrently reducing parental
      smoking.

PMID- 22157232
TI  - Lack of an association between three tagging SNPs within the FTO gene and smoking
      behavior.
AB  - INTRODUCTION: Using genome-wide screening, a polymorphism within the second
      intron of the FTO gene (rs2302673) was found to be associated with smoking habits
      in females. In a population-based, cross-sectional study, we analyzed three
      tagging FTO single-nucleotide polymorphisms (SNPs) for their association with
      smoking behavior. METHODS: Subjects from the Czech post-MONICA study, including
      1,191 adult males (32.1% smokers) and 1,368 adult females (22.5% smokers) were
      included in this study. Smoking habits were obtained through questionnaire data
      analysis, and three FTO tagging SNPs were genotyped (rs17817449: intron 1,
      rs2302673: intron 2, and rs17818902: intron 3). RESULTS: We detected slightly
      lower frequencies (p = .043) of the GG genotype of the rs17818902 SNP in males
      who quit smoking compared with others. However, the significance disappeared
      after adjusting for multiple testing. Within the entire population, or in either
      males or females alone, we failed to detect a significant difference between
      other FTO genotypes and smoking status. Also, the number of cigarettes smoked per
      day was independent of individual FTO genotypes in both genders. CONCLUSIONS: We
      did not find an association between the FTO gene tagging variants and smoking
      status. FTO is unlikely to be a major genetic determinant of smoking status.

PMID- 22157233
TI  - Protein-losing enteropathy associated with or without systemic autoimmune
      disease:  what are the differences?
AB  - OBJECTIVE: The aim of our study was to compare protein-losing enteropathy (PLE)
      associated with or without systemic autoimmune (SA) diseases. METHODS: Patients
      diagnosed with PLE were selected, and their clinical characteristics, laboratory,
      endoscopic and imaging characteristics, treatment, and outcome were analyzed.
      RESULTS: From 2001 to 2010, 74 patients (60 patients with SA disease) with a
      female predominance were diagnosed with PLE. The SA group tended to be younger,
      presented early (4.3 vs. 7 weeks, P=0.08), and had significantly more
      mucocutaneous-articular involvement (16.7 vs. 0%, P<0.05; 50 vs. 0%, P<0.02; 43.3
      vs. 0%, P<0.01), compared with the other group, which showed more weight loss
      (64.3 vs. 25%, P<0.01), malaise and fatigue (57.1 vs. 28.3%, P<0.02), and tended
      to have more gastrointestinal (GI) symptoms. The SA group was associated with
      lymphopenia (0.8 vs. 2.7 * 109/l, P<0.01), hyperglobulinemia (43 vs. 31.2 IU/l,
      P<0.04), lactate dehydrogenase (511.1 vs. 393.5 IU/l, P<0.05), hematuria (48.3
      vs. 7.1%, P<0.01), and pyuria (23.3 vs. 0%, P<0.03), whereas the non-SA group had
      a higher platelet count (402 vs. 262.5 * 109/l, P<0.01) and alkaline phosphatase
      (111 vs. 78.2 IU/l, P<0.03) on admission. A subgroup analysis of patients with SA
      disease showed that more lupus patients had pericardial effusion (14.6 vs. 0%,
      P=0.08), polyarthritis (50 vs. 16.7%, P=0.02), lower C3 level (0.5 vs. 0.85 mg/l,
      P<0.01), antinuclear factors (89.6 vs. 58.3%, P<0.01), and antiextractable
      nuclear antigen antibody (73.3 vs. 37.5%, P<0.03), whereas nonlupus patients had
      higher C-reactive protein (87.9 vs. 40 mg/l, P<0.01) and more antineutrophil
      cytoplasmic antibody (ANCA) (60 vs. 3%, P=0.00). Thirty-seven (71%) patients with
      SA disease had diffuse nonerosive erythematous GI mucosa with chronic
      inflammatory cells in the lamina propria layer, and 12 (85.7%) patients without
      SA disease had focal lesions. The treatment response was comparable between the
      two groups. However, the time required to normalize the serum albumin level (6.3
      vs. 12.3 months, P=0.02) of patients with SA disease was much shorter than that
      of the non-SA group and those of inflammatory markers, specifically, C-reactive
      protein and complement C3, of its own group (6.3 vs. 11.6 vs. 12.1 months,
      P<0.04). More patients without SA disease had infective episodes during the
      management period (14.3 vs. 1.7%, P<0.01). CONCLUSION: Patients with PLE
      associated with SA disease tend to have a distinct clinical syndrome with regard
      to the extent of clinical manifestations and laboratory, endoscopic, and
      histological features compared with those without. Patients without SA disease
      are more prone to develop complications and mortality. However, both can be
      effectively treated with comparable treatment response.

PMID- 22157234
TI  - Serum concentrations of human insulin-like growth factor-1 and levels of insulin
      like growth factor-binding protein-5 in patients with nonalcoholic fatty liver
      disease:  association with liver histology.
AB  - OBJECTIVE: In this study, we aimed to investigate the relationship between the
      histological features of nonalcoholic fatty liver disease (NAFLD) and serum
      insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding
      protein-5 (IGFBP-5) to determine the usefulness of this relationship in clinical
      practice. MATERIALS AND METHODS: Serum samples were collected from 92 patients
      with biopsy-proven NAFLD and 51 healthy controls and serum levels of IGF-1 and
      IGFBP-5 were assayed by enzyme-linked immunosorbent assay. RESULT: Serum IGFBP-5
      levels were correlated with liver steatosis, fibrosis, and nonalcoholic
      steatohepatitis scores. IGF-1 levels were significantly decreased in patients
      with moderate-to-severe fibrosis compared with patients with no or mild fibrosis.
      CONCLUSION: Serum IGFBP-5 levels may be useful to differentiate both advanced
      fibrosis and definite nonalcoholic steatohepatitis from other NAFLD groups. Also,
      serum IGF-1 levels may be useful to differentiate advanced fibrosis in patients
      with NAFLD.

PMID- 22157235
TI  - The continuum of intestinal CD4+ T cell adaptations in host-microbial mutualism.
AB  - How a mutualistic relationship between the intestinal microbiota and intestinal T
      cell compartments is established is important, as a breakdown of intestinal T
      cell homeostasis may cause inflammatory bowel diseases. A number of studies have
      shown that different bacterial species modulate the intestinal CD4(+) T cell
      compartment in different ways. We performed mechanistic in vivo studies that
      demonstrated the crucial requirement for regulatory T cells (Treg) and
      interleukin-10 (IL-10) in the induction of intestinal T cell homeostasis even
      following colonization with a completely benign microbiota. In the absence of a
      functional Treg response or IL-10 receptor signaling, the same bacteria that
      induced a Treg response in wild-type animals now induced T helper type 17
      responses, without intestinal inflammation. Therefore, Treg, IL-10 and Th17 are
      crucial regulatory mechanisms in the intestine not only for controlling
      inflammation, but also to establish a continuum of CD4(+) T cell homeostasis upon
      commensal colonization.

PMID- 22157237
TI  - Protective effect of Lactobacillus rhamnosus 231 against N-Methyl-N'-nitro-N
      nitrosoguanidine in animal model.
AB  - The protective effect of Lactobacillus rhamnosus 231 (Lr 231) against potent
      carcinogen N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG) in the rat model is
      studied. Daily feeding with Lr 231 improved the body weight of male Wistar rats
      compared with control groups. Fecal azoreductase (p < 0.001) and nitroreductase
      (p < 0.01) enzyme activity decreased significantly in Lr 231 group in comparison
      with control groups that received only phosphate buffer or MNNG. Oral
      administration of MNNG led to a significant increase in Glutathione transferase
      (GST) while Glutathione reductase (GSH) showed decreased activity. Conversely,
      feeding Lr 231 showed significantly increased GSH and decreased GST activity in
      comparison to the MNNG group, emphasizing the protection provided by Lr 231
      against MNNG. Histopathological analysis of liver, spleen and colon showed
      decreased signs of inflammation in the Lr 231 group. The present study highlights
      that inclusion of active Lr 231 in regular diets could be used to prevent MNNG
      induced colon carcinoma.

PMID- 22157236
TI  - Bacterial adaptation to the gut environment favors successful colonization:
      microbial and metabonomic characterization of a simplified microbiota mouse
      model.
AB  - Rodent models harboring a simple yet functional human intestinal microbiota
      provide a valuable tool to study the relationships between mammals and their
      bacterial inhabitants. In this study, we aimed to develop a simplified
      gnotobiotic mouse model containing 10 easy-to-grow bacteria, readily available
      from culture repositories, and of known genome sequence, that overall reflect the
      dominant commensal bacterial makeup found in adult human feces. We observed that
      merely inoculating a mix of fresh bacterial cultures into ex-germ free mice did
      not guarantee a successful intestinal colonization of the entire bacterial set,
      as mice inoculated simultaneously with all strains only harbored 3 after 21 d.
      Therefore, several inoculation procedures were tested and levels of individual
      strains were quantified using molecular tools. Best results were obtained by
      inoculating single bacterial strains into individual animals followed by an
      interval of two weeks before allowing the animals to socialize to exchange their
      commensal microbes. Through this procedure, animals were colonized with almost
      the complete bacterial set (9/10). Differences in the intestinal composition were
      also reflected in the urine and plasma metabolic profiles, where changes in
      lipids, SCFA, and amino acids were observed. We conclude that adaptation of
      bacterial strains to the host's gut environment (mono-colonization) may predict a
      successful establishment of a more complex microbiota in rodents.

PMID- 22157238
TI  - Crohn disease-associated Escherichia coli promote gastrointestinal inflammatory
      disorders by activation of HIF-dependent responses.
AB  - Crohn disease (CD) ileal lesions are colonized by adherent-invasive E. coli
      (AIEC) that locally induce inflammation. Hypoxia inducible factor (HIF)-1alpha
      protein is expressed in acute and chronically inflamed site; however the
      molecular basis of this expression is not fully understood. The aim of the study
      was to access whether AIEC induce HIF-1alpha expression and to study the
      consequence of HIF-1alpha expression on the onset of Crohn disease pathogenesis.
      We show that HIF-1alpha is maximally expressed in inflamed ileal epithelium of CD
      patients. CEACAM6, a protein that acts as a receptor of AIEC, is expressed in
      this particular condition. Using CEABAC 10 transgenic mice that express CEACAM6,
      we show that AIEC bacteria, but not non-pathogenic E. coli K12, induce the
      production of HIF-1alpha protein and the activation of VEGF/VEGFR signaling.
      Downstream analyses on human intestinal epithelial cells silenced for hif-
      1alpha, highlight the crucial role of this protein in production of pro
      angiogenic factors. This study highlights the crucial role of AIEC bacteria as
      promoter of inflammatory disorders of the gastrointestinal tract and provides
      clear evidence that HIF-1alpha protein plays a major role in mediating this
      effect.

PMID- 22157239
TI  - Fecal microbiota transplantation for relapsing Clostridium difficile infection in
      26 patients: methodology and results.
AB  - GOALS: We aim to present a data detailing our success with fecal microbiota
      transplantation (FMT) and to provide a simple treatment protocol. BACKGROUND:
      Relapse is a common problem in patients treated for Clostridium difficile
      infection, often requiring prolonged courses of oral vancomycin with limited
      alternative treatment options. Administration of the entire fecal flora from a
      healthy individual to restore beneficial physiological species is referred to as
      FMT (also termed fecal bacteriotherapy or stool transplant). Although introduced
      over 50 years ago with high cure rates in published case series, FMT is neither
      routine practice nor widely available to patients. STUDY: Twenty-six patients
      with relapsing C. difficile infection underwent FMT over a 28-month period. FMT
      was performed during colonoscopy by direct infusion of minimally processed donor
      stool. RESULTS: Twenty-four female and 2 male patients underwent FMT. The mean
      duration of CDI was 12.6 months (range, 4 to 84 mo) before FMT. These patients
      have been followed for a mean duration of 10.7 months (range, 2 to 30 mo). Twenty
      four patients have remained free of significant diarrhea or CDI. One experienced
      loose stool and resumed vancomycin despite remaining C. difficile negative; she
      developed CDI recurrence 11 months post-FMT after taking cephalexin. Another had
      diarrhea 2 months post-FMT. Stool was not tested for C. difficile; she received 1
      week of vancomycin and CDI did not recur after this. CONCLUSIONS: FMT through
      colonoscopy was simple, safe, and 92% effective in preventing further diarrhea or
      CDI relapse in this group of 26 patients with recurrent CDI.

PMID- 22157240
TI  - The effect of a multispecies probiotic mixture on the symptoms and fecal
      microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double
      blind, placebo-controlled trial.
AB  - BACKGROUND: The clinical effect of probiotics on irritable bowel syndrome (IBS)
      is still controversial. AIMS: We aimed to evaluate the effects of a probiotic
      mixture on IBS symptoms and the composition of fecal microbiota in patients with
      diarrhea-dominant IBS (D-IBS). METHODS: Fifty patients with D-IBS were randomized
      into placebo or probiotic mixture (Lactobacillus acidophilus, Lactobacillus
      plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, Bifidobacterium
      lactis, Bifidobacterium longum, and Streptococcus thermophilus 1.0*10 CFU)
      groups. Treatment was taken daily for 8 weeks. The primary outcome was adequate
      relief (AR) of overall IBS symptoms, which was assessed weekly for 10 weeks. A
      responder was defined as a patient who experienced AR for at least half of the 10
      week study period. Secondary outcomes included the effects on individual
      symptoms, stool parameters, and IBS quality of life. The fecal flora compositions
      were analyzed by polymerase chain reaction denaturing gradient gel
      electrophoresis (DGGE). RESULTS: The proportion of AR was consistently higher in
      the probiotics group than in the placebo group throughout the 10-week period
      (P<0.05). The proportion of responders was significantly higher in the probiotics
      group than in the placebo group (48% vs. 12%, P=0.01). Stool consistency improved
      significantly in the probiotics group compared with the placebo group. Percent
      changes in individual symptom scores were similar in the 2 groups, but IBS
      quality of life improvement tended to be higher in the probiotics group.
      Comparison of denaturing gradient gel electrophoresis profiles of fecal flora
      showed that the concordance rate between bacterial compositions before and after
      treatment was significantly higher in the probiotics group than in the placebo
      group (69.5% vs. 56.5%, P=0.005). CONCLUSIONS: The probiotic mixture was
      effective in providing AR of overall IBS symptoms and improvement of stool
      consistency in D-IBS patients, although it had no significant effect on
      individual symptoms. The therapeutic effect of probiotics is associated with the
      stabilization of intestinal microbiota.

PMID- 22157241
TI  - Photopheresis in the treatment of cutaneous T-cell lymphoma:  current status.
AB  - Cutaneous T-cell lymphoma is the overall name for a group of malignancies in
      which malignant T-lymphocytes localize at the skin. Of the current 20 recognized
      subtypes of the disease, the most common are mycosis fungoides and Sezary
      syndrome. Extracorporeal photopheresis (ECP), an immunomodulating procedure that
      treats pheresed blood with a photoactive agent, received US Food and Drug
      Administration approval in 1988 as a medical device for the treatment of CTCL
      patients, one of many treatment options for such patients. This was followed in
      2003 by guidelines in the United Kingdom that recommended ECP for patients with
      advanced CTCL, particularly after skin-directed treatment options have failed.
      ECP is now under investigation for use in patients with earlier stages of CTCL.
      This article reviews the evolution of the ECP technique--for example, the most
      recent generation of the device requires a lower extracorporeal volume of blood
      than the previous version did, thus making it possible for more patients to be
      candidates for the procedure. In addition, there has been progress in
      understanding how ECP works at the cellular level.

PMID- 22157242
TI  - Development of type 2 diabetes caused by a deficiency of a tRNA(lys)
      modification.
AB  - Genetic variations in the cdk5 regulator associated protein 1-like 1 (cdkal1)
      gene have been identified in whole genome association studies as a risk factor
      for the development of type 2 diabetes (T2D). A recent study showed that Cdkal1
      was a mammalian methythiotransferase, which specifically synthesizes 2-methylthio
      N (6)-threonylcarbamoyladenosine (ms (2)t (6)A) at position 37 of tRNA(lys)(UUU).
      The ms (2)t (6)A modification in tRNA(lys)(UUU) was important for the accurate
      decoding of its cognate codon. In pancreatic beta-cell-specific Cdkal1 knockout
      (Cdkal1 KO) mice, a deficiency of ms (2)t (6)A caused the mistranslation of a Lys
      codon in proinsulin, resulting in improper processing. The mice showed a decrease
      in insulin secretion and glucose intolerance. In addition, the mistranslation
      contributed to the expression of the endoplasmic reticulum (ER) stress response
      in Cdkal1-deficient beta-cells. Furthermore, Cdkal1 KO mice were hypersensitive
      to high-fat diet-induced glucose intolerance, as well as the ER stress response.
      These findings might potentially explain the molecular pathogenesis of T2D in
      patients carrying Cdkal1 variations. 

PMID- 22157243
TI  - Primary cutaneous sarcomatoid anaplastic large-cell lymphoma.
AB  - A case of primary cutaneous anaplastic large-cell lymphoma with sarcomatoid
      histologic features is described. Sarcomatoid anaplastic large-cell lymphoma has
      previously been reported only ten times in the literature. It is a diagnostic
      challenge because of sarcomatoid features that include atypical spindle-shaped
      cells, a storiform architecture, and a mucinous stroma. Clues pointing toward the
      diagnosis of lymphoma may be very subtle. Awareness of this entity can lead to
      more accurate recognition of a potentially fatal disease.

PMID- 22157244
TI  - New clinical and histological patterns of acute disseminated histoplasmosis in
      human immunodeficiency virus-positive patients with acquired immunodeficiency
      syndrome.
AB  - Histoplasmosis has attained increasing relevance in the past 3 decades because of
      the appearance of the human immunodeficiency virus (HIV). In most immunocompetent
      persons, the infection is asymptomatic or can produce a respiratory condition
      with symptoms and radiological images similar to those observed in pulmonary
      tuberculosis; in non-HIV+ immunocompromised patients, it can cause respiratory
      symptoms or evolve into a disseminated infection. The same can occur in acquired
      immunodeficiency syndrome (AIDS) patients. We have observed a series of HIV+
      patients with AIDS who presented with cutaneous histoplasmosis and in whom the
      clinical and histopathological features were highly unusual, including variable
      mucocutaneous lesions that were difficult to diagnose clinically. These patients
      displayed unusual, previously undescribed, histological patterns, including
      lichenoid pattern, nodular pseudomyxoid pattern, pyogenic granuloma-like pattern,
      perifollicular pattern, and superficial (S), mid (M), and deep perivascular
      dermatitis; and more commonly encountered patterns, such as histiocytic lobular
      panniculitis and focal nodular dermatitis. The novel histopathological patterns
      of cutaneous involvement by histoplasmosis seen in these patients resembled other
      common inflammatory and infectious conditions and required a high level of
      suspicion and the application of special stains for organisms for confirmation.
      These new, clinical, and histological findings do not seem to be commonly
      encountered in HIV- patients infected with the fungus but seem to be displayed
      most prominently in HIV+ patients with AIDS.

PMID- 22157245
TI  - FOXP3 in sequential biopsies of progressive mycosis fungoides.
AB  - A recent report has suggested that the numbers of regulatory T cells correlate
      with stage of disease and prognosis in mycosis fungoides (MF). To evaluate the
      role of FOXP3+ Tregs in different stages of MF, we investigated sequential
      biopsies in 14 patients with patch/plaque and subsequent tumor stage using FOXP3
      antibody. Our data neither show a significant difference in the percentage of
      FOXP3+ cells between patch/plaque and tumor stage biopsies of MF nor demonstrate
      a predictable shift of Tregs in the course of disease progression. Additionally,
      we could observe FOXP3-expressing neoplastic cells in 4 patch/plaque stage
      biopsies, where they represented almost 100% of the epidermotropic infiltrate.
      Only in one of these patients, FOXP3+ cells could also be detected in the tumor
      stage biopsy, indicating that FOXP3 expression can be acquired or lost during the
      course of the disease, comparable to other phenotypic markers.

PMID- 22157246
TI  - Anaplastic oligodendroglioma involving the subcutaneous tissue of the scalp: 
      report of an exceptional case and review of the literature.
AB  - Anaplastic oligodendroglioma [AO, World Health Organization (WHO) grade III] is
      an uncommon but aggressive tumor of the central nervous system that typically
      arises in adults. Clinically, patients present with seizures, and the prognosis
      is considered poor. Metastatic spread is extremely rare. We report an exceptional
      case of AO with extracranial scalp involvement, which arose in a patient with
      recurrent primary AO of the brain after chemoradiation, multiple cranial surgical
      resections, and subsequent scalp reconstruction. On histopathology, the
      subcutaneous tissue of the scalp contained several clusters and infiltrating
      cords of relatively small, epithelioid cells with hyperchromatic nuclei, scant
      eosinophilic cytoplasm, and perinuclear halos, which gave the cells a
      characteristic fried-egg appearance. By immunohistochemistry, the lesional cells
      were positive for glial fibrillary acidic protein and S-100. It is likely that
      surgical implantation and direct extracranial extension after craniotomy were the
      mechanisms responsible for dissemination of the patient's tumor.

PMID- 22157247
TI  - Expression of mesenchymal-related genes by the bovine trophectoderm following
      conceptus attachment to the endometrial epithelium.
AB  - In the course of experiments to identify and characterize the factors that
      function in bovine conceptuses during peri-attachment periods, various
      transcripts related to the epithelial-mesenchymal transition (EMT) were found. In
      this study, RNA was extracted from different sets of days 17, 20, and 22 (day
      0=day of estrous) bovine conceptuses and subjected to real-time PCR analysis as
      well as Western blotting, from which abundances of N-cadherin (CDH2), vimentin,
      matrix metalloproteinase 2 (gelatinase A, 72 kDa gelatinase, 72 kDa type IV
      collagenase) (MMP2), and matrix metallopeptidase 9 (gelatinase B, 92 kDa
      gelatinase, 92 kDa type IV collagenase) (MMP9) mRNAs were determined on day 22,
      concurrent with (CDH1) mRNA and protein downregulation. Transcription factors in
      EMT processes were then analyzed and changes in snail homolog 2 (Drosophila)
      (SNAI), zinc finger E-box binding homeobox 1 (ZEB1), zinc finger E-box binding
      homeobox 2 (ZEB2), twist homolog 1 (Drosophila) (TWIST1), twist homolog 2
      (Drosophila) (TWIST2), and Kruppel-like factor 8 (KLF8) transcripts were found in
      day 22 conceptuses, while confirming SNAI2 expression by Western blotting.
      Immunohistochemical analysis revealed that the day 22 trophectoderm expressed the
      mesenchymal markers N-cadherin and vimentin as well as the epithelial marker
      cytokeratin. In attempts to identify the molecular mechanisms by which the
      trophectoderm expressed EMT-related genes, growth factor receptors associated
      with EMT were analyzed. Upregulation of the growth factor receptor transcripts,
      fibroblast growth factor receptor 1 (FGFR1), platelet-derived growth factor
      receptor, alpha polypeptide (PDGFRA), platelet-derived growth factor receptor,
      beta polypeptide (PDGFRB), and transforming growth factor, beta receptor II
      (70/80 kDa) (TGFBR2) mRNAs, was found on day 22. The analysis was extended to
      determine the integrin (ITG) transcripts and found high levels of integrin, alpha
      4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor) (ITGA4), integrin, alpha 8
      (ITGA8), integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) (ITGB3), and
      integrin, beta 5 (ITGB5) mRNAs on day 22. These observations indicate that after
      the conceptus-endometrium attachment, EMT-related transcripts as well as the
      epithelial marker cytokeratin were present in the bovine trophectoderm and
      suggest that the implantation process for noninvasive trophoblasts requires not
      only extracellular matrix expression but also partial EMT.

PMID- 22157248
TI  - Re-evaluation of histological findings of nonparasitic splenic cysts.
AB  - OBJECTIVE: The pathogenesis of nonparasitic splenic cysts (NPSCs) has not been
      clarified completely. The aim of this multinational and multicentre retrospective
      study was to further elucidate the origin of NPSCs. METHODS: From 1980 to 2006,
      50 children and adolescents were surgically treated for NPSC at six paediatric
      surgical centres in four European countries. The initial histology report of 35
      NPSCs, 22 epidermoid cysts, 11 pseudocysts or post-traumatic cysts and two
      mesothelial cysts was available. Additional re-evaluation, including
      immunohistochemistry, to detect cytokeratin, carcino-embrionic antigen and
      mesothelioma antibody in the inner surface of the cysts was carried out. Special
      attention was given to the possibility of preceding trauma to the splenic area
      and whether it played a role in the genesis of NPSC. RESULTS: The pathological re
      evaluation showed 30 epidermoid cysts, four mesothelial cysts and one pseudocyst.
      Immunohistology revealed eight epidermoid and two mesothelial linings of the
      cysts in those 11 patients in whom pseudocyst was diagnosed originally. No
      pseudocyst was documented in those patients who had a history of previous blunt
      abdominal trauma but was not proved by ultrasound and computed tomography scan.
      CONCLUSION: In contrast with the prevailing belief, it has been demonstrated that
      NPSCs are congenital in origin, and there is no clinically proven evidence that
      trauma does play a role in their genesis.

PMID- 22157249
TI  - Bibliography. Cataract surgery and lens implantation. Current world literature.

PMID- 22157251
TI  - Influence of abdominal pressure on respiratory and abdominal organ function.
AB  - PURPOSE OF REVIEW: Intra-abdominal hypertension (IAH) and abdominal compartment
      syndrome (ACS) have been realized as severe complications in the intensive care
      patient. Laparoscopic surgery in older and more obese patients increases the risk
      of IAH and ACS. RECENT FINDINGS: The incidence of IAH may be larger than thought
      of being approximately one-third of mechanically ventilated intensive care
      patients. In shock/trauma, three-fourths of all patients may suffer from IAH.
      Kidney and liver may dysfunction and the gut barrier may be impeded, permitting
      spread of inflammation to other organs. IAH and ACS have an impact on respiratory
      mechanics and may impede ventilation and require higher ventilation pressures
      than under normal conditions. Prone position and alternating (asynchronous)
      ventilation may moderate the IAH. In addition, surgical decompression should be
      considered. SUMMARY: In view of the frequent occurrence of IAH in intensive care,
      the need of better understanding of the mechanisms behind IAH is a prerequisite
      for better treatment. Respiratory mechanics are affected but may also indicate
      routes of ventilatory treatment to lower IAH.

PMID- 22157252
TI  - Ventilator-induced lung injury:  the role of gene activation.
AB  - PURPOSE OF REVIEW: Ventilator-induced lung injury (VILI) is a ubiquitous
      iatrogenic clinical problem in critical care. Aside from avoiding large tidal
      volumes, little progress has been made in identifying effective clinical
      strategies to minimize this injury. With recent rapid development in
      bioinformatics and high-throughput molecular technology, the genetic basis of
      lung injury has been intensively investigated. This review will describe recent
      insights and potential therapies developed in the field. RECENT FINDINGS: Much
      progress has been made in delineating the possible genes and gene products
      involved in VILI through various mechanisms such as early induced genes,
      capillary leak, apoptosis, fibrin deposition, inflammatory cytokines, oxidative
      stress, disrupted angiogenesis, and neutrophil infiltration. Some studies have
      translated bench findings to the bedside in an attempt to identify clinically
      important genetic susceptibility, which could aid in the identification of at
      risk individuals who might benefit from careful titration of mechanical
      ventilation. Genetic insights also provide candidate pharmaceutical approaches
      that may ameliorate VILI in the future. SUMMARY: Much relevant information exists
      for investigators and clinicians interested in VILI. Future research will
      interlink evolving data to provide a more integrated picture of the molecular
      mechanisms involved in VILI enabling translation of the most promising candidate
      therapies.

PMID- 22157253
TI  - Unproven clinical evidence in mechanical ventilation.
AB  - PURPOSE OF REVIEW: To describe the management principles that have not been
      verified or tested but nonetheless successfully guide the logic of everyday
      practice at the bedside. RECENT FINDINGS: The importance of physiologic data
      integration, timing, and careful patient selection has been emphasized by
      reanalyses of recent clinical trials that individually have led to controversial
      conclusions and recommendations. SUMMARY: The practitioner of intensive care
      often has no choice but to make difficult decisions and to select a course of
      treatment that remains unguided by specific, scenario-specific evidence from
      observational studies and clinical trials. Experience gathered over many prior
      encounters combined with solid physiologic understanding helps to develop guiding
      principles and unproven rules of management that serve well in confronting
      complex, ever changing problems of acute illness. Although some element of trial
      and error is unavoidable, careful monitoring, short loop feedback, and mid-course
      corrections render many logic-driven and experience-driven decisions relatively
      safe to implement and often effective in an uncertain, high-stakes environment.

PMID- 22157254
TI  - Stress and strain within the lung.
AB  - PURPOSE OF REVIEW: To describe the physiological meaning and the clinical
      application of the lung stress and strain concepts. RECENT FINDINGS: The end
      inspiratory plateau pressure and ratio of tidal volume/ideal body weight are
      inadequate surrogates for the end-inspiratory stress (equal to the transpulmonary
      pressure) and the end-inspiratory strain (change in lung volume relative to the
      resting volume). For a given plateau pressure or tidal volume/ideal body weight,
      stress and strain may vary largely due to the variability of chest wall elastance
      and the resting lung volume. The injurious limits of stress and strain in healthy
      lungs are reached when stress and strain reach the total lung capacity. This
      occurs when the resting lung volume (the baby lung in case of acute respiratory
      distress syndrome) is increased by two-fold to three-fold. As these limits are
      rarely reached in clinical practice and damage has been reported with stress and
      strain well below this upper limit, this implies the presence in the lung
      parenchyma of regions which act as stress raisers or pressure multipliers. These
      are primarily linked to the inhomogeneous distribution of local stress and
      strain. SUMMARY: End-inspiratory stress and strain, as well as the lung
      inhomogeneity and the stress raisers, must be taken in account when setting
      mechanical ventilation.

PMID- 22157255
TI  - The role of high-frequency oscillatory ventilation in the treatment of acute
      respiratory failure in adults.
AB  - PURPOSE OF REVIEW: High-frequency oscillatory ventilation (HFOV) is increasingly
      used in adults with the acute respiratory distress syndrome (ARDS), who remain
      hypoxemic during conventional mechanical ventilation. In this review, we will
      summarize the trials evaluating HFOV in adults with ARDS and discuss issues
      relevant to the clinician regarding the use of HFOV. RECENT FINDINGS: Several
      observational and randomized trials support the safety of HFOV and improvements
      in oxygenation in adult patients with severe ARDS, who remain hypoxemic during
      conventional mechanical ventilation. SUMMARY: HFOV theoretically meets the goals
      of lung-protective ventilation. On the basis of the current evidence, HFOV is
      associated with improvements in oxygenation in severe, adult ARDS. However,
      whether HFOV influences mortality, length of ICU stay, ventilator-free days,
      quality-of-life factors and is cost-effective remains to be determined. Large,
      prospective, randomized controlled trials such as the ongoing OSCAR and OSCILLATE
      trials will help further define the role of HFOV in adult ARDS.

PMID- 22157256
TI  - Thigh-length versus knee-length compression stockings for deep vein thrombosis
      prophylaxis in the inpatient setting.
AB  - Deep vein thrombosis may be a complication of extended length hospital stays.
      Immobilized patients, such as patients in the postoperative period, are at
      particularly high risk of developing a deep vein thrombosis, which can be
      associated with high levels of morbidity and mortality. Due to this, prevention
      of deep vein thrombosis is of great importance in the inpatient setting.
      Compression stockings have proven to play an important role in prophylaxis and
      may be used in their knee-length or thigh-length variety. Although randomized
      trials have studied the efficacy of both varieties in prevention of deep vein
      thrombosis, selection is often made without regard to evidence. This meta
      analysis pools the findings of current studies comparing knee-length and thigh
      length compression stockings for deep vein thrombosis prophylaxis. A fixed
      effects model was used for this study with a two-sided alpha-error less than 0.05
      considered to be statistically significant. When both varieties of compression
      stockings are compared, thigh-length stockings offer a risk reduction in deep
      vein thrombosis development when compared with knee-length (odds ratio 1.197,
      confidence interval 0.983-1.458). This, however, is an insignificant finding.
      This analysis concludes that current data does not favor either thigh-length or
      knee-length compression stockings when it comes to prophylaxis of deep vein
      thrombosis.

PMID- 22157257
TI  - New quantitative total protein S-assay system for diagnosing protein S type II
      deficiency:  clinical application of the screening system for protein S type II
      deficiency.
AB  - Venous thromboembolism (VTE) incidence is rising rapidly in Japan with lifestyle
      westernization and aging. Deficiency of protein S, an important blood coagulation
      regulator, is a risk factor for VTE. Protein S deficiency prevalence in Asians is
      approximately 10 times that in Caucasians and that of protein S type II
      deficiency, associated with the protein S Tokushima mutation (K155E), is quite
      high in Japan. However, currently available methods for measuring protein S are
      not precise enough for detection of this deficiency. We developed a novel assay
      system for precise simultaneous determinations of total protein S activity and
      total protein S antigen level, using a general-purpose automated analyzer,
      allowing protein S-specific activity (ratio of total protein S activity to total
      protein S antigen level) to be calculated. Mean specific activity was 0.99 for
      samples from healthy individuals but 0.69 or less (mean-3SD) in protein S type II
      deficient and warfarin-treated samples, but was 1.0 in an estrogen-treated sample
      with significantly decreased protein S antigen. Protein S gene analyses in
      healthy individuals with specific activity 0.69 or less revealed the K155E
      mutation in all three. These results show our new assay system to be an effective
      screening tool for protein S type II deficiency. This system can also be used in
      an automated analyzer, facilitating numerous sample measurements, and is, thus,
      applicable to regular medical checkups and diagnosing VTE. Such applications
      would potentially contribute to early detection of protein S type II deficiency,
      and, thereby, to thrombosis prevention.

PMID- 22157258
TI  - Effect of enhanced external counterpulsation treatment on mean platelet volume in
      patients affected by ischemic chronic heart failure.
AB  - Mean platelet volume (MPV) is increased in chronic heart failure (CHF) and is an
      independent predictor of mortality in CHF patients. It is not known whether
      enhanced external counterpulsation (EECP) therapy leads to decreased MPV values
      or not. The purpose of this study was to examine the effects of EECP on platelet
      count and MPV values and to assess the influence of MPV on the risk of death and
      recurrent ischemic events in ischemic CHF patients. A total of 68 ischemic heart
      failure patients with CHF symptoms and refractory angina pectoris were included
      in the study, 47 consecutive patients (39 males and eight females) aged 44-82
      years. Although follow-up period started after completion of EECP in treated
      patients, control group follow-up started at the end of 7-week treatment without
      EECP. All patients were monitored for a mean duration of 13 +/- 8 months (range,
      1-36 months). The primary endpoints of the study were effects of EECP treatment
      on platelets after treatment period (7 weeks) and the recurrence of ischemic
      events. Secondary endpoint was cardiovascular death during the follow-up period.
      We observed a significant increase in platelet count and decrease in MPV levels
      (P = 0.044 and P = 0.004, respectively) in the control group. There were no
      significant differences in platelet count and MPV levels in the EECP group (P >
      0.05). After the treatment period, New York Heart Association functional
      classification (2.60 +/- 0.75 vs. 1.72 +/- 0.68, P < 0.001) and Canadian
      Cardiovascular Society functional classification of angina (2.50 +/- 0.90 vs.
      1.60 +/- 0.74, P < 0.001) improved in patients with EECP treatment. In our study,
      we found that EECP therapy had a neutral effect on MPV values and platelet count.

PMID- 22157259
TI  - Endothelial progenitor cells:  current development of their paracrine factors in
      cardiovascular therapy.
AB  - Endothelial progenitor cells were initially considered to radically alter the
      concepts of adult tissue angiogenesis for their contribution of incorporation
      into new blood vessels. Nevertheless, controversy arises over their mechanism of
      action due to rare cell population and decreased number and impaired activity
      under pathological changes. Recent studies show that endothelial progenitor cells
      also function in a paracrine manner by secreting multiple cytokines and growth
      factors, but the beneficial paracrine signals remain partially unidentified. In
      this review, we provide an overview of varieties and signal pathways of factors
      secreted by endothelial progenitor cells and further present the prospect of new
      ways to encourage cardiovascular protection such as neovascularization,
      reendothelialization of larger vessels, and myocardial remodeling based on the
      paracrine factors.

PMID- 22157260
TI  - 2-hydroxy-4'-methoxychalcone inhibits proliferation and inflammation of human
      aortic smooth muscle cells by increasing the expression of peroxisome
      proliferator-activated receptor gamma.
AB  - Chalcone is a class of flavonoid compounds that are widely biosynthesized in
      plants. Epidemiological studies suggest that increased intake of flavonoids from
      fruits and vegetables reduces the risk of cardiovascular disease. However, the
      effect of chalcone on cardiovascular diseases has not been fully investigated.
      The aims of this study were to evaluate the antiatherosclerotic effect of 2
      hydroxy-4'-methoxychalcone (AN07, a synthetic chalcone derivate) and to
      investigate its potential pharmacological mechanisms. Oxidized low-density
      lipoprotein (Ox-LDL) has been reported to stimulate proliferation of human aortic
      smooth muscle cells and that is one of the mechanisms resulting in
      atherosclerosis. In this study, we demonstrate that AN07 significantly inhibits
      the Ox-LDL-induced proliferation of human aortic smooth muscle cells. This effect
      is mediated via the inhibition of p44/42 mitogen-activated protein kinase and E
      twenty six 1 phosphorylations. In the effect of anti-inflammation, AN07 decreases
      the Ox-LDL-stimulated upregulation of interleukin (IL) 1beta and IL-6. In
      addition, AN07 acts synergistically with rosiglitazone and pioglitazone to
      inhibit the Ox-LDL-induced proliferation of human aortic smooth muscle cells and
      upregulation of cyclin D1, cyclin D3, IL-1beta, and IL-6. These effects are a
      result of an increase in peroxisome proliferator-activated receptor gamma mRNA
      and protein expression stimulated by AN07 in human aortic smooth muscle cells. In
      conclusion, the chalcone derivate AN07 has versatile therapeutic potential
      against atherosclerosis by acting as peroxisome proliferator-activated receptor
      gamma inducer, p44/42 mitogen-activated protein kinase inhibitor, and cell cycle
      blocker.

PMID- 22157263
TI  - Dysphagia, oral telangiectasia, and Raynaud syndrome.

PMID- 22157261
TI  - A nonpeptide angiotensin II type 2 receptor agonist does not attenuate
      postmyocardial infarction left ventricular remodeling in mice.
AB  - Cardiac overexpression of the angiotensin II type 2 receptor (AT2 R) attenuates
      left ventricular (LV) remodeling after myocardial infarction (MI) in transgenic
      mice. We hypothesized that a novel nonpeptide AT2 R agonist, compound 21 (C21),
      would attenuate post-MI LV remodeling. Fifty-nine mice were studied for 28 days
      after 1-hour surgical occlusion-reperfusion of the left anterior descending
      coronary artery. Immediately thereafter, 23 mice received 0.3 mg.kg.d of C21 via
      Alzet osmotic minipump, 16 received 10 mg.kg.d of the AT1 R antagonist
      candesartan in drinking water, and 20 were untreated controls. Cardiac magnetic
      resonance imaging measured ejection fraction (EF), LV end-systolic, and end
      diastolic volumes (ESVI and EDVI) indexed to weight serially post MI. Infarct
      size was measured on day 1 by late gadolinium-enhanced cardiac magnetic resonance
      imaging. At baseline, heart rate, blood pressure, EDVI, ESVI, and EF were similar
      between groups. Mean infarct size (42%-45% of LV mass) was similar between
      groups. C21-treated animals demonstrated adverse LV remodeling (increased EDVI
      and ESVI at all post-MI time points) compared with control. Candesartan therapy
      preserved left ventricular EF at day 28 compared with the C21-treated group.
      Thus, direct stimulation of the AT2 R by C21 at 0.3 mg.kg.d does not attenuate
      post-MI LV remodeling in reperfused MI in mice.

PMID- 22157265
TI  - Monostotic fibrous dysplasia of the inferior turbinate.

PMID- 22157264
TI  - Benign paroxysmal positional vertigo is not a prognostic factor in sudden
      sensorineural hearing loss.
AB  - OBJECTIVE: Little is known concerning the role of benign paroxysmal positional
      vertigo (BPPV) as a prognostic factor for sudden sensorineural hearing loss
      (SSNHL). The purpose of this study is to analyze the hearing recovery in patients
      who have SSNHL with BPPV compared with those who have SSNHL without BPPV. The
      study also documented the relative incidence of each semicircular canal
      involvement. STUDY DESIGN: Case-control study. SETTING: Academic tertiary
      otologic practice. SUBJECTS AND METHODS: Ninety patients diagnosed with SSNHL
      with vertigo were enrolled. Clinical characteristics such as gender, age, and
      pure tone audiogram threshold were compared between group A (SSNHL with BPPV, n =
      17) and group B (SSNHL without BPPV, n = 73). The frequency of each canal
      involvement was compared between group A and another 111 patients with BPPV only
      (group C). The proportion of patients with hearing recovery was compared between
      patients with or without BPPV, and between those with or without canal paresis.
      RESULTS: Patients in group A did not display significant differences in the sex
      ratio, mean age, or initial results of pure tone audiogram threshold compared
      with those in group B. Most patients with SSNHL with BPPV had lateral canal
      canalithiasis (64.7%). The presence of BPPV had no influence on the recovery of
      hearing. CONCLUSIONS: The clinical characteristics of patients with SSNHL with
      BPPV were not different from those with SSNHL without BPPV. The lateral canal was
      the most frequently involved, and the presence or absence of BPPV had no dramatic
      impact on the outcome of SSNHL.

PMID- 22157266
TI  - Giant cell arteritis in Mexican patients.
AB  - BACKGROUND: Giant cell arteritis (GCA) is the most common primary systemic
      vasculitis worldwide, although it seems to be very rare in some areas, such as
      Latin America. OBJECTIVES: The objective of the study was to describe the
      clinical, laboratory, and treatment features in a Mexican Mestizo population with
      GCA. METHODS: Retrospective data chart review (1989-2010). RESULTS: Twenty-two
      patients with GCA were identified, 18 women and 4 men. Mean age was 73 (SD, 7.9)
      years. Diagnosis was made at a mean of 67 (SD, 83.6) days from symptom onset.
      Most frequent presenting symptoms included headache (90%), constitutional
      symptoms (86%), and polymyalgia rheumatica (59%). Severe cranial ischemic
      complications were present in 32%. Amaurosis fugax and blindness were present in
      36% and 27%, respectively. High erythrocyte sedimentation rate was present in 89%
      of patients. Rapid response to prednisone treatment was seen, but in 10 patients,
      relapse occurred, possibly related to fast tapering. Additional treatment was
      methotrexate (n = 8), azathioprine (n = 5), and cyclophosphamide (n = 3). Median
      follow-up was 242 (SD, 214) weeks. CONCLUSIONS: Giant cell arteritis is rarely
      recognized in Latin America. We report on characteristics of GCA in a population
      of Mexican Mestizos, as ours is the largest series to be reported from Latin
      America so far. When compared with other series, age at onset is similar, females
      are more affected, and although a good response to corticosteroid treatment was
      seen, a higher frequency of amaurosis fugax and blindness was observed,
      accounting for an unfavorable functional outcome in 6 (27%) of 22 patients.

PMID- 22157267
TI  - Contrast-enhanced magnetic resonance imaging positively impacts the management of
      some patients with rheumatoid arthritis or suspected RA.
AB  - OBJECTIVE: Early diagnosis of rheumatoid arthritis (RA) is important given the
      availability of highly effective disease-modifying antirheumatic (DMARD)
      medications, including biologics. However, because of associated risks and cost,
      accurately assessing disease activity is critical. Because magnetic resonance
      imaging (MRI) can detect synovitis and bone marrow edema, both of which may
      precede erosion development, we sought to determine the impact of enhanced MRI on
      patient management in a group of patients referred for MRI by rheumatologists.
      MATERIALS AND METHODS: After institutional review board approval, we evaluated
      all hand MRI examinations referred by the rheumatology department for synovitis
      evaluation between September 2007 and May 2009. The magnetic resonance images
      were classified as positive or negative and later reviewed by 2 musculoskeletal
      radiologists. A musculoskeletal radiologist and rheumatologist jointly reviewed
      the patients' medical records to determine the following: (1) Did the MRI
      findings alter treatment? (2) Were the treatment alterations beneficial? RESULTS:
      The study included 48 patients (39 women and 9 men) with a mean age of 51 years
      (range, 18-79 years). Significant management changes initially occurred in 79%
      (23/29) of the positive (DMARDs added in 20) and in 11% (2/19) of the negative MR
      examinations with average follow-up of ~300 days. Eighty percent (16/20) of the
      patients with DMARDs added experienced symptom improvement, none of the patients
      whose medications were discontinued experienced symptom relapse, and 18% (4/22)
      of patients without initial therapeutic changes required delayed treatment
      modifications. CONCLUSIONS: Enhanced MRI significantly altered clinical
      management in 50% of these patients with RA or suspected RA. Therefore, when the
      clinical picture in a patient with RA or suspected RA is unclear, enhanced MRI
      can provide useful guidance for treatment modifications.

PMID- 22157268
TI  - Assessment of tophus size: a comparison between physical measurement methods and
      dual-energy computed tomography scanning.
AB  - BACKGROUND: Dual-energy computed tomography (DECT) has recently been described as
      a sensitive method to detect urate deposits in patients with gout. OBJECTIVES:
      The aim of this study was to compare the reproducibility of DECT with various
      physical measurement methods of tophus size assessment. METHODS: Sixty-four tophi
      from 25 patients were analyzed. Each tophus was assessed by 2 independent
      observers using Vernier calipers and tape measure. All patients proceeded to DECT
      scanning of both feet. Urate volume within index tophi was assessed by 2
      independent observers using automated DECT volume assessment software (n = 55
      tophi). Five patients returned within 1 week for repeat physical assessment of
      tophus size. Dual-energy computed tomography scans from the returning patients
      were scored twice by both observers. Intraobserver and interobserver
      reproducibility was assessed by intraclass correlation coefficient (ICC) and
      limits-of-agreement analysis. RESULTS: Overall, DECT was more reproducible than
      the physical methods with interobserver ICCs for DECT of 0.95, for calipers 0.78,
      and for tape measurement 0.88, and intraobserver ICCs for DECT of 1.00, for
      calipers 0.75, and for tape measurement 0.91. Vernier caliper and tape
      measurements correlated highly with each other (rs = 0.84, P < 0.0001) but less
      well with DECT (for index tophi, r(s) = 0.46, P = 0.004 for both). Large
      variation was observed in the amount of urate deposits documented by DECT in
      tophi of similar physical size. CONCLUSIONS: Dual-energy computed tomography
      scanning is a highly reproducible method for measuring urate deposits within
      tophi. This imaging modality reveals the composition of tophi that contain
      variable urate deposits embedded within soft tissue.

PMID- 22157269
TI  - Eosinophilic esophagitis and pharyngitis presenting as mass lesion in a patient
      with inactive rheumatoid arthritis.
AB  - We describe here a case of longstanding rheumatoid arthritis (RA) presenting with
      recurrent episodes of epigastric pain, melena, nonprogressive dysphagia, and
      hoarseness associated with persistent peripheral blood eosinophilia. Her RA was
      clinically inactive, but she had significant lymphadenopathy and
      hepatosplenomegaly. Computed tomographic scan of the thorax revealed
      circumferential wall thickening extending from the oropharynx to the
      gastroesophageal junction with a large polypoidal mass projecting into the lumen
      of the stomach. Histology revealed infiltration of the esophageal mucosa by
      eosinophils with a density of 40 to 80 per high-power field. The stratified
      squamous epithelium of the pharyngeal mucosa was also infiltrated by eosinophils
      with a density of more than 100 per high-power field. Eosinophilic esophagitis
      and pharyngitis were diagnosed, and the patient was administered corticosteroids
      and hydroxyurea, following which her symptoms resolved. On repeat imaging, there
      was significant reduction in esophageal wall thickening and luminal dilatation.
      There are few reports of tissue eosinophilia in association with RA, but the
      pathogenesis and any definite association with RA are not clear.

PMID- 22157270
TI  - Inflammatory and noninflammatory arthropathy in patients with 18q deletion
      syndrome.
AB  - A 7-year-old girl with 18q deletion syndrome developed chronic progressive
      polyarticular inflammatory arthropathy. Atypical features of her arthritis
      included lack of morning stiffness, absence of pain and discomfort, normal acute
      phase reactants, and the presence of clinodactyly, low-set thumbs, metatarsus
      adductus of her feet, and overriding nontender swollen toes. She had a positive
      antinuclear antibody test, negative rheumatoid factor and anti-cyclic
      citrullinated peptide, and undetectable immunoglobulin A level. Magnetic
      resonance imaging of the right knee and the result of the synovial biopsy were
      consistent with synovitis. She was treated with naproxen, short course of
      prednisone, and methotrexate with good clinical response that plateaued over
      time. We analyzed the scarce reports of inflammatory arthropathy in 18q deletion
      syndrome and proposed an outline for investigating arthropathies in patients with
      chromosomal aberrations.

PMID- 22157271
TI  - Systemic lupus erythematosus with Sjogren syndrome compared to systemic lupus
      erythematosus alone: a meta-analysis.
AB  - OBJECTIVES: This study aimed to compare the difference of the clinical and
      laboratory features of the patients between the combined systemic lupus
      erythematosus (SLE) and Sjogren syndrome (SLE-SS) and SLE only. MATERIALS AND
      METHODS: A systematic literature search was performed to identify the articles as
      to SLE with SS between 1970 and May 2011. The demographics, pertinent clinical,
      and laboratory data were extracted from 6 publications, and a meta-analysis was
      performed. The pooled odds ratios and 95% confidence interval were computed for
      the variability of these parameters between SLE-SS and SLE. RESULTS: A total of 6
      studies were included, consisting of 2489 patients with SLE and 444 with SLE-SS,
      and the estimated prevalence of the latter was 17.8%. Patients with SLE-SS were
      older and more often had associated oral ulcers and arthritis. In contrast,
      proteinuria (odds ratio = 1.77; 95% confidence interval, 1.39-2.25; P < 0.0001)
      was more common in SLE alone than SLE-SS, and central nervous system involvement
      tended to be more common. Anti-double-stranded DNA antibodies were equally
      prevalent in both groups. Anti-SSA/Ro and anti-SSB/La antibodies were more
      frequent, and anti-Sm and anti-cardiolipin antibodies were less prevalent in SLE
      SS than SLE alone. CONCLUSIONS: There are significant variances in certain
      clinical and laboratory aspects between SLE-SS and SLE. This combined disease of
      SLE-SS has distinct features with relatively less major internal organ
      involvement but has more specific autoantibody profile and favorable clinical
      outcome.

PMID- 22157272
TI  - Systemic vasculitis in a patient with atopic dermatitis, eosinophilia, pulmonary
      renal syndrome, and positive myeloperoxidase antibody: a classification
      conundrum.

PMID- 22157273
TI  - Candida albicans prosthetic shoulder joint infection in a patient with rheumatoid
      arthritis on multidrug therapy.

PMID- 22157274
TI  - Fatal acquired hemophilia A in a patient with rheumatoid arthritis treated with
      adalimumab.

PMID- 22157275
TI  - Acute polyarthritis as sole manifestation of meningococcal disease.

PMID- 22157276
TI  - Acute arthritis associated with rotavirus gastroenteritis: an unusual
      extraintestinal manifestation of a common enteric pathogen.

PMID- 22157277
TI  - Methotrexate-related minor adverse effects in rheumatoid arthritis: more than a
      nuisance.

PMID- 22157278
TI  - Rituximab associated pneumonitis in antineutrophil cytoplasmic antibody
      associated vasculitis.
AB  - Rituximab is gaining use in the treatment of antineutrophil cytoplasmic antibody
      associated vasculitis. We report the first case of rituximab-induced pneumonitis
      in a patient with antineutrophil cytoplasmic antibody-associated vasculitis. Our
      patient with granulomatosis with polyangiitis (Wegener granulomatosis) had a
      relapse complicated by diffuse alveolar hemorrhage and acute kidney injury. His
      treatment included rituximab, steroids, cyclophosphamide, and plasmapheresis. Two
      weeks after his second dose of rituximab, he developed an acute deterioration in
      respiratory function. Rituximab-induced pneumonitis was diagnosed on a
      combination of computed tomography imaging, bronchoalveolar lavage, and negative
      tests for active vasculitis and infection. He was treated with a course of high
      dose corticosteroids with improvement in respiratory function, computed
      tomography imaging of his chest, and inflammatory markers. Acute drug-induced
      pneumonitis is a rare but serious complication of rituximab. Distinguishing this
      complication from alveolar hemorrhage or pulmonary infection may be difficult.
      This diagnosis needs to be considered early in the right clinical context.

PMID- 22157279
TI  - Kashin-Beck disease in Sichuan, China: report of a pilot open therapeutic trial.
AB  - OBJECTIVE: The objective of the study was to identify adults with symptomatic
      Kashin-Beck disease (KBD) and observe the efficacy and safety of diclofenac
      sodium, naproxen, and glucosamine hydrochloride in these adult patients in Rang
      tang (Sichuan Province), China. SUBJECTS AND METHODS: One hundred eighty-three
      adult patients with KBD were enrolled into this open study. Patients were
      randomized to receive diclofenac sodium 50 mg twice a day (BID), naproxen 300 mg
      BID, or glucosamine hydrochloride 750 mg BID for 6 weeks. The primary efficacy
      parameters evaluated were the visual analog pain scale, Western Ontario and
      McMaster Universities Osteoarthritis Index, and physical function subscores.
      Assessment of daily self-care activities and physician and patient global overall
      efficacy were also recorded. RESULTS: Diclofenac sodium, naproxen, and
      glucosamine hydrochloride all reduced the joint pain and improved physical
      function and daily self-care activities in adult patients with KBD. Visual analog
      pain scale scores, Western Ontario and McMaster Universities Osteoarthritis Index
      pain scores, physical function scores, and daily self-care activities subscore
      differences were statistically significant compared with baselines (P < 0.05).
      Comparison studies among the 3 agents showed no statistically significant
      difference in efficacy. The incidences of gastrointestinal adverse reactions were
      18% and 14% in the diclofenac sodium group and the glucosamine hydrochloride
      group, respectively, which tended to be lower than the naproxen group (29%).
      However, the differences were not statistically significant. CONCLUSIONS: This
      report documents characteristic findings in these patients. Diclofenac sodium,
      naproxen, and glucosamine hydrochloride produced substantial improvements over
      baseline in pain relief, physical function, and daily self-care activities in
      these open observations of adult patients with KBD.

PMID- 22157281
TI  - Current world literature.

PMID- 22157283
TI  - Introduction for: frontiers of personalized cancer medicine.

PMID- 22157280
TI  - Neural correlates associated with cognitive decline in late-life depression.
AB  - OBJECTIVES: Persistent cognitive impairment (PCI) after remission of depressive
      symptoms is a major adverse outcome of late-life depression (LLD). The purpose of
      this study was to examine neural substrates associated with PCI in LLD. DESIGN:
      Longitudinal study. SETTING: Outpatient depression treatment study at Duke
      University. PARTICIPANTS: Twenty-three patients with LLD completed a 2-year
      follow-up study, and were in a remitted or partially remitted state at Year 2.
      METHODS: At first entry to the study (Year 0), all participants had a functional
      magnetic resonance imaging scan while performing an emotional oddball task. For
      the purpose of this report, the primary functional magnetic resonance imaging
      outcome was brain activation during target detection, which is a measure of
      executive function. The Consortium to Establish a Registry for Alzheimer's
      Disease neuropsychological battery was used to assess cognitive status yearly,
      and the Montgomery-Asberg Depression Rating Scale was used to assess severity of
      depression at Year 0 and every 6 months thereafter for 2 years. We investigated
      changes in brain activation at Year 0 associated with PCI over 2 years. RESULTS:
      Patients with PCI at the 2-year follow-up date had significantly decreased
      activation at Year 0 in the dorsal anterior cingulate cortex, hippocampus,
      inferior frontal cortex, and insula compared to non-PCI patients. CONCLUSIONS:
      Our results suggest individuals who have LLD with PCI have decreased activation
      in the similar neural networks associated with the development of Alzheimer
      disease among nondepressed individuals. Measuring neural activity in these
      regions in individuals with LLD may help identify patients at-risk for cognitive
      impairment.

PMID- 22157284
TI  - Inherited colorectal cancer syndromes.
AB  - Colorectal cancer is the most common gastrointestinal malignancy and the second
      leading cause of cancer death in both men and women in the United States. Most
      colorectal cancer cases diagnosed annually are due to sporadic events, but up to
      5% are attributed to known monogenic disorders including Lynch syndrome, familial
      adenomatous polyposis, MYH-associated polyposis, and the rare hamartomatous
      polyposis syndromes. These inherited colorectal cancer syndromes confer a
      markedly increased risk for the development of multiple cancers, and predictive
      genetic testing is available to identify mutation carriers and at-risk family
      members. Through personalized strategies for diagnosis and management, a
      substantial reduction in morbidity and mortality has been appreciated among
      patients at highest risk for the development of colorectal cancer.

PMID- 22157286
TI  - Application of proteomics to cancer early detection.
AB  - Strategies to achieve personalized medicine and improve public health encompass
      assessment of an individual's risk for disease, early detection, and molecular
      classification of disease resulting in an informed choice of the most appropriate
      treatment instituted at an early stage of disease development. An unmet need in
      this field for which proteomics is well suited to make a major contribution is
      the development of blood-based tests for early cancer detection. This is
      illustrated in proteomic studies of epithelial cancer that encompass analysis of
      specimens collected both at the time of diagnosis and specimens collected before
      onset of symptoms that are particularly suited for the identification of early
      detection markers. This overarching effort benefits from the availability of
      plasmas from subject cohorts and of engineered mouse models that are sampled at
      early stages of tumor development. Integration of findings from plasma with tumor
      tissue and cancer cell proteomic and genomic data allows elucidation of
      signatures in plasma for altered signaling pathways. The discovery and further
      development of early detection markers take advantage of the availability of in
      depth quantitative proteomics methods and bioinformatics resources for data
      mining.

PMID- 22157285
TI  - The genetics of cancer risk.
AB  - One hundred years ago, decades before the discovery of the structure of DNA,
      debate raged regarding how human traits were passed from one generation to the
      next. Phenotypes, including risk of disease, had long been recognized as having a
      familial component. Yet it was difficult to reconcile genetic segregation as
      described by Mendel with observations exhaustively documented by Karl Pearson and
      others regarding the normal distribution of human characteristics. In 1918, R. A.
      Fisher published his landmark article, "The Correlation Between Relatives on the
      Supposition of Mendelian Inheritance," bridging this divide and demonstrating
      that multiple alleles, all individually obeying Mendel's laws, account for the
      phenotypic variation observed in nature.Since that time, geneticists have sought
      to identify the link between genotype and phenotype. Trait-associated alleles
      vary in their frequency and degree of penetrance. Some minor alleles may approach
      a frequency of 50% in the human population, whereas others are present within
      only a few individuals. The spectrum for penetrance is similarly wide. These
      characteristics jointly determine the segregation pattern of a given trait,
      which, in turn, determine the method used to map the trait. Until recently,
      identification of rare, highly penetrant alleles was most practical.
      Revolutionary studies in genomics reported over the past decade have made
      interrogation of most of the spectrum of genetic variation feasible.The following
      article reviews recent discoveries in the genetic basis of inherited cancer risk
      and how these discoveries inform cancer biology and patient management. Although
      this article focuses on prostate cancer, the principles are generic for any
      cancer and, indeed, for any trait.

PMID- 22157287
TI  - Prognostic determinants in prostate cancer.
AB  - Clinical outcomes in prostate cancer are heterogeneous, and given the high
      prevalence of the disease, there is a pressing need to identify clinically useful
      markers of prognosis. Many clinical, pathological, molecular, and genetic factors
      have been investigated in this capacity, although relatively few are routinely
      used. With a growing understanding of the molecular pathogenesis of prostate
      cancer, there is the potential that the next generation of makers will prove
      sufficiently robust to guide the optimal management of men with prostate cancer.
      Here, we review the various clinical and molecular prognostic determinants in
      prostate cancer.

PMID- 22157289
TI  - Emerging technologies for improved stratification of cancer patients: a review of
      opportunities, challenges, and tools.
AB  - Cancer is a heterogeneous collection of diseases with wild variation in etiology,
      pathogenesis, response to therapy, and prognosis. Sources of variation are
      frequently obscure. Current practice attempts to classify tumors by tissue of
      origin and extent of disease through staging such that more risky tumors can be
      managed with more aggressive treatments. Modest inroads have been made with
      biomarkers to further characterize groups of tumors with important
      characteristics such as response to selected drugs. However, biomarker-driven
      decisions are relatively few when examining the maze of clinical decisions in the
      care of cancer patients. Against this backdrop, waves of researchers have
      unleashed a vast array of new technologies, with the goal of better
      characterization of the inherent diversity of tumors. This review outlines the
      use of cancer biomarkers and emerging technologies to stratify patients with a
      focus on the challenges and opportunities of next-generation nucleic acid
      sequencing approaches in oncology.

PMID- 22157288
TI  - Circulating tumors cells as biomarkers: progress toward biomarker qualification.
AB  - Personalized cancer medicine requires the development of tumor-specific
      biomarkers to optimize selection of targeted therapies and to better assess
      response to therapy. Current efforts in several tumor types have shown that
      patients in whom circulating tumor cells (CTCs) are detected have an inferior
      prognosis relative to those in whom CTCs are not detected and that the
      elimination or decrease of CTCs following treatment is associated with improved
      clinical outcomes. Technological advances in the detection, isolation, capture,
      and characterization of CTCs from phlebotomy samples obtained in a routine
      clinical practice setting have enabled the evaluation of different CTC
      biomarkers. Unmet needs in cancer diagnosis and treatment where CTC biomarkers
      have been studied include determining prognosis, assessing the effects of
      treatment, and as a source of tumor for the biologic identification and
      characterization of determinants to predict sensitivity to one form of treatment
      versus another and to understand mechanisms of treatment resistance.At present,
      there is no single definition of a CTC and no single CTC "biomarker." Rather,
      multiple assays (tests) are in development for CTC biomarkers. However, before
      the role of any biomarker in medical decision making can be determined, it is
      essential that the assays used to measure the biomarker are analytically
      validated in a sequence of trials to generate the evidence to support the
      biomarker's use in the given context of use. It is against this background that
      this review focuses on the process of developing CTC biomarker assays, with the
      objective of outlining the necessary steps to qualify specific CTC tests for
      medical decision making in clinical practice or drug development. The potential
      for point-of-care tests is clear.

PMID- 22157290
TI  - Evolution of therapies for chronic myelogenous leukemia.
AB  - The clinical outcome for patients with chronic myelogenous leukemia (CML) has
      changed dramatically in the past 15 years. This has been due to the development
      of tyrosine kinase inhibitors (TKIs), compounds that inhibit the activity of the
      oncogenic BCR-ABL1 protein. Imatinib was the first TKI developed for CML, and it
      led to high rates of complete cytogenetic responses and improved survival for
      patients with this disease. However, approximately 35% of patients in chronic
      phase treated with imatinib will develop resistance or intolerance to this drug.
      The recognition of the problem of imatinib failure led to the design of second
      generation TKI (dasatinib, nilotinib, and bosutinib). These drugs are highly
      active in the scenario of imatinib resistance or intolerance. More recently, both
      nilotinib and dasatinib were approved for frontline use in patients with chronic
      phase CML. Ponatinib represents the last generation of TKI, and this drug has
      been developed with the aim of targeting a specific BCR-ABL1 mutation (T315I),
      which arises in the setting of prolonged TKI therapy and leads to resistance to
      all commercially available TKI. Parallel to the development of specific drugs for
      treating CML, major advances were made in the field of disease monitoring and
      standardization of response criteria. In this review, we summarize how therapy
      with TKI for CML has evolved during the last decade.

PMID- 22157291
TI  - Development of an effective therapy for chronic myelogenous leukemia.
AB  - Targeted small-molecule drugs have revolutionized treatment of chronic myeloid
      leukemia (CML) during the last decade. These agents interrupt a constitutively
      active BCR-ABL, the causative agent for CML, by interfering with adenosine 5'
      triphosphate-dependent ABL tyrosine kinase. Although the efficacy of tyrosine
      kinase inhibitors (TKIs) has resulted in overall survival of greater than 90%,
      TKIs are not curative. Moreover, no currently approved TKIs are effective against
      the T315I BCR-ABL variant. However, a new generation of TKIs with activity
      against T315I is on the horizon. We will highlight the clinical utility of
      historical CML therapeutics, those used today (first- and second-generation
      TKIs), and discuss treatment modalities that are under development. Recent
      advances have illuminated the complexity of CML, especially within the marrow
      microenvironment. We contend that the key to curing CML will involve strategies
      beyond targeting BCR-ABL because primitive human CML stem cells are not dependent
      on BCR-ABL. Ultimately, drug combinations or exploiting synthetic lethality may
      transform responses into definitive cures for CML.

PMID- 22157292
TI  - Genomics of acute myeloid leukemia.
AB  - The acute myeloid leukemia (AML) genome has been the subject of intensive
      research over the past 4 decades. New technologies, enabling characterization of
      the AML genome at increased resolution, have revealed deeper layers of complexity
      that have provided insights into the biological basis of this disease, nominated
      targets for therapy, and identified biomarkers predictive of response to therapy
      or long-term prognosis. Still, our understanding of AML genomics is incomplete.
      Recent publications have demonstrated that whole genome sequencing of primary AML
      samples is feasible and can detect novel, clinically relevant mutations. New
      insights are emerging from this work, including the clonal heterogeneity of this
      disease and clonal evolution that occurs over time. Some of the novel mutations
      are highly recurrent (>20% of patients), but there appears to be a continuum of
      mutation frequency down to rare (<5%) or even singleton mutations that may be
      relevant for the biology of this disease. Large cohorts of well-annotated samples
      are needed to establish mutation frequencies, implicate biological pathways, and
      demonstrate genotype-phenotype correlations. Although many technical and
      logistical challenges must be overcome, the capacity of whole genome sequencing
      to detect all classes of inherited and acquired genetic abnormalities makes it an
      attractive candidate for development as a clinical diagnostic test.

PMID- 22157293
TI  - BRCA mutation testing in determining breast cancer therapy.
AB  - BRCA mutation-associated breast cancer differs from sporadic breast cancer with
      regard to future cancer risks and sensitivity to systemic therapies. Now that
      rapid genetic testing for BRCA1 and BRCA2 mutations is available at the time of
      breast cancer diagnosis, BRCA mutation status can be considered when making
      treatment and prevention decisions for BRCA mutation carriers with breast cancer.
      This article reviews surgical options for management of affected BRCA mutation
      carriers with emphasis on the risks of ipsilateral recurrence and contralateral
      breast cancer. The roles of breast-conserving surgery, prophylactic mastectomy,
      and oophorectomy are reviewed. In addition, the sensitivity of BRCA mutation
      associated breast cancer to endocrine therapy, platinum chemotherapy, and poly
      (ADP-ribose) polymerase inhibitors is reviewed.

PMID- 22157294
TI  - Genomics of adjuvant therapy for breast cancer.
AB  - Therapeutic decision for adjuvant systemic therapy for breast cancer involves
      assessment of baseline risk and estimated benefit from systemic therapy.
      Molecular profiling studies have clearly demonstrated heterogeneity of
      chemotherapy response across different molecular subtypes of breast cancer. Meta
      analyses of publicly available data from gene expression profiling studies have
      demonstrated that breast cancer can be divided into 4 basic categories based on
      expression levels of estrogen receptor (ER), HER2, and proliferation-associated
      genes; ER-, HER2+, ER+/HER2-/low proliferation, and ER+/HER2-/high proliferation.
      Notably ER- or HER2+ tumors are associated with high levels expression of
      proliferation genes, although there is a wide spectrum of expression levels of
      proliferation genes among ER+/HER2- tumors. Estrogen receptor-positive/HER2-/low
      proliferation tumors are associated with a favorable prognosis. Synthetic lethal
      screening approach has demonstrated that most of the chemotherapeutic agents do
      not have specific molecular targets. Therefore, it could be hypothesized that
      chemosensitivity would be largely dictated by proliferation activity of tumor
      cells. Therefore, tumors with ER-, HER2+, or ER+/HER2-/high proliferation gene
      expression profile can be categorized as chemosensitive tumors, whereas ER+/HER
      /low proliferation tumors categorized as chemoresistant. Therefore, clinical
      utility of gene expression profiling is mainly in aiding the chemotherapy
      decision for ER+ patients. Although evidence from prospective randomized clinical
      trials are lacking, because of the excellent baseline prognosis of patients with
      ER+/HER2-/low proliferation tumors when treated with endocrine therapy and
      because of scientific evidence of chemoresistance of these tumors, a comfort zone
      has been reached among oncologists to allow clinical use of gene expression tests
      to identify patients who do not require chemotherapy among node-negative ER+
      patients. However, these tools are still probabilistic at best in their
      performances, and one cannot exactly predict which patient will have recurrence
      after assigned therapies until the time of recurrence. Therefore, strategies have
      to be established to identify patients who will fail standard chemoendocrine
      therapies among high-risk patients (ER+/HER2-/high proliferation, HER2+, or ER-)
      before recurrence events. Neoadjvant therapy can provide such venue because
      regardless of regimens used the prognosis of those achieving complete
      pathological response is excellent. Postneoadjuvant setting can be then used for
      patients with gross residual disease to test novel therapeutic agents.

PMID- 22157295
TI  - BRAF inhibitors and melanoma.
AB  - Selective BRAF inhibitors have recently emerged as a new standard treatment for
      patients with metastatic melanoma harboring activating BRAF mutations. Inhibition
      of the MAP kinase pathway and initial evidence of antitumor effects are very
      reliably observed. However, many patients experience short-lived responses,
      whereas others are durable. An overall survival benefit has been established for
      them, BRAF in it, the agents that have advanced furthest in clinical development.
      Nonetheless, attention has immediately turned to understanding de novo and
      acquired resistance and effort to develop rational combination therapy that will
      further improve patient outcomes. Opportunities for combining BRAF inhibitors
      with other signal transduction inhibitors as well as targeted therapies with
      distinct mechanisms of action are discussed.

PMID- 22157297
TI  - Implementing personalized medicine in a cancer center.
AB  - In 2006, the Moffitt Cancer Center partnered with patients, community clinicians,
      industry, academia, and 17 hospitals in the United States to begin a personalized
      cancer care initiative called Total Cancer Care. Total Cancer Care was designed
      to collect tumor specimens and clinical data throughout a patient's lifetime,
      with the goal of finding "the right treatment, for the right patient, at the
      right time." Because Total Cancer Care is a partnership with the patient and
      involves collection of clinical data and tumor specimens for research purposes, a
      formal protocol and patient consent process was developed, and an information
      technology platform was constructed to provide a robust "warehouse" for clinical
      and molecular profiling data. To date, more than 76,000 cancer patients from
      Moffitt and consortium medical centers have been enrolled in the protocol. The
      Total Cancer Care initiative has developed many of the capabilities and resources
      that are building the foundation of personalized medicine.

PMID- 22157298
TI  - Conditioning on intermediates in perinatal epidemiology.
AB  - It is common practice in perinatal epidemiology to calculate gestational-age
      specific or birth-weight-specific associations between an exposure and a
      perinatal outcome. Gestational age or birth weight, for example, might lie on a
      pathway from the exposure to the outcome. This practice of conditioning on a
      potential intermediate has come under critique for various reasons. First, if one
      is interested in assessing the overall effect of an exposure on an outcome, it is
      not necessary to stratify, and indeed, it is important not to stratify, on an
      intermediate. Second, if one does condition on an intermediate, to try to obtain
      what might conceived of as a "direct effect" of the exposure on the outcome, then
      various biases and paradoxical results can arise. It is now well documented
      theoretically and empirically that, when there is an unmeasured common cause of
      the intermediate and the outcome, associations adjusted for the intermediate are
      subject to bias. In this paper, we propose 3 approaches to facilitate valid
      inference when effects conditional on an intermediate are in view. These 3
      approaches correspond to (i) conditioning on the predicted risk of the
      intermediate, (ii) conditioning on the intermediate itself in conjunction with
      sensitivity analysis, and (iii) conditioning on the subgroup of individuals for
      whom the intermediate would occur irrespective of the exposure received. The
      second and third approaches both require sensitivity analysis, and they result in
      a range of estimates. Each of the 3 approaches can be used to resolve the "birth
      weight paradox" that exposures such as maternal smoking seem to have a protective
      effect among low-birth-weight infants. The various methodologic approaches
      described in this paper are applicable to a number of similar settings in
      perinatal epidemiology.

PMID- 22157299
TI  - Commentary: The wizard of odds.

PMID- 22157301
TI  - Exposure to trihalomethanes in drinking water and small-for-gestational-age
      births.
AB  - BACKGROUND: Trihalomethanes in drinking water have been associated with higher
      occurrence of small-for-gestational-age (SGA) births, although results have been
      inconsistent. METHOD: We geocoded residential address for mother of live,
      singleton, term births to 33 water distribution systems in a large metropolitan
      area of New South Wales, Australia (314,982 births between 1998 and 2004) and
      classified births into <10th percentile and >= 10 percentile of weight for
      gestational age. Mean trihalomethane exposure was estimated by trimester and for
      the entire pregnancy based on monthly sampling in each of the 33 water
      distribution systems. We estimated the relative risk (RR) of SGA for exposure to
      trihalomethanes using log-binomial regression adjusting for confounding. RESULTS:
      SGA births increased with mother's third-trimester exposure to chloroform (RR =
      1.04 [95% confidence interval = 1.02-1.06], across an interquartile range [IQR] =
      25 MUg/L) and bromodichloromethane (1.02 [1.01-1.04], 5 MUg/L). Larger
      associations were found for SGA less than third percentile. Smoking modified the
      effects of trihalomethane exposure, with generally larger associations in births
      to nonsmoking mother and weaker or protective associations in births to smoking
      mothers. CONCLUSIONS: : Mothers' exposures during pregnancy to total
      trihalomethane as well as to chloroform and bromodichloromethane were associated
      with SGA. These associations were modified by maternal smoking during pregnancy.

PMID- 22157296
TI  - Targeted therapies for lung cancer: clinical experience and novel agents.
AB  - Although lung cancer remains the leading cancer killer in the United States,
      recently a number of developments indicate future clinical benefit. These include
      evidence that computed tomography-based screening decreases lung cancer
      mortality, the use of stereotactic radiation for early-stage tumors, the
      development of molecular methods to predict chemotherapy sensitivity, and genome
      wide expression and mutation analysis data that have uncovered oncogene
      "addictions" as important therapeutic targets. Perhaps the most significant
      advance in the treatment of this challenging disease is the introduction of
      molecularly targeted therapies, a term that currently includes monoclonal
      antibodies and small-molecule tyrosine kinase inhibitors. The development of
      effective targeted therapeutics requires knowledge of the genes and pathways
      involved and how they relate to the biologic behavior of lung cancer. Drugs
      targeting the epidermal growth factor receptor, anaplastic lymphoma kinase, and
      vascular endothelial growth factor are now U.S. Food and Drug Administration
      approved for the treatment of advanced non-small cell lung cancer. These agents
      are generally better tolerated than conventional chemotherapy and show dramatic
      efficacy when their use is coupled with a clear understanding of clinical data,
      mechanism, patient selection, drug interactions, and toxicities. Integrating
      genome-wide tumor analysis with drug- and targeted agent-responsive phenotypes
      will provide a wealth of new possibilities for lung cancer-targeted therapeutics.
      Ongoing research efforts in these areas as well as a discussion of emerging
      targeted agents being evaluated in clinical trials are the subjects of this
      review.

PMID- 22157302
TI  - Commentary: Lead's latest cousins: childhood central nervous system development
      and the environment.

PMID- 22157303
TI  - Commentary: A niche for ecologic studies in environmental epidemiology.

PMID- 22157304
TI  - Evaluation of screening tests for detecting Chlamydia trachomatis: bias
      associated with the patient-infected-status algorithm.
AB  - In recent years, the evaluation of nucleic acid amplification tests (NAATs) for
      detecting Chlamydia trachomatis and Neisseria gonorrhea is based on a methodology
      called the patient-infected-status algorithm (PISA). In the simplest version of
      PISA, 4 test-specimen combinations (comparator tests) are used to define the gold
      standard. If a person shows a positive result by any 2 or more of these 4
      comparator tests, the person is classified as infected; otherwise, the person is
      considered to be uninfected. A new test is then compared with this diagnostic
      algorithm. PISA-based sensitivity and specificity estimates of nucleic acid
      amplification tests have been published in the medical and microbiologic
      literature and have been included in FDA-approved package inserts of NAATs for
      detecting C. trachomatis. Using simulations, we compare 2 versions of the patient
      infected-status algorithm with latent-class models and an imperfect gold
      standard. We show that the PISA can produce highly biased test-performance
      parameter estimates. In a series of simulated scenarios, none of the 95%
      confidence intervals for PISA-based estimates of sensitivity and prevalence
      contained the true values. In addition, the PISA-based estimates of sensitivity
      and specificity change markedly as the true prevalence changes. We recommend that
      PISA should not be used for estimating the sensitivity and specificity of tests.

PMID- 22157305
TI  - Commentary: Reference-test bias in diagnostic-test evaluation: a problem for
      epidemiologists, too.

PMID- 22157307
TI  - Commentary: Weighing up the dead and missing: reflections on inverse-probability
      weighting and principal stratification to address truncation by death.

PMID- 22157306
TI  - Fecal indicators in sand, sand contact, and risk of enteric illness among
      beachgoers.
AB  - BACKGROUND: Beach sand can harbor fecal indicator organisms and pathogens, but
      enteric illness risk associated with sand contact remains unclear. METHODS: In
      2007, visitors at 2 recreational marine beaches were asked on the day of their
      visit about sand contact. Ten to 12 days later, participants answered questions
      about health symptoms since the visit. F+ coliphage, Enterococcus, Bacteroidales,
      fecal Bacteroides, and Clostridium spp. in wet sand were measured using culture
      and molecular methods. RESULTS: We analyzed 144 wet sand samples and completed
      4999 interviews. Adjusted odds ratios (aORs) were computed, comparing those in
      the highest tertile of fecal indicator exposure with those who reported no sand
      contact. Among those digging in sand compared with those not digging in sand, a
      molecular measure of Enterococcus spp. (calibrator cell equivalents/g) in sand
      was positively associated with gastrointestinal (GI) illness (aOR = 2.0 [95%
      confidence interval (CI) = 1.2-3.2]) and diarrhea (2.4 [1.4-4.2]). Among those
      buried in sand, point estimates were greater for GI illness (3.3 [1.3-7.9]) and
      diarrhea (4.9 [1.8-13]). Positive associations were also observed for culture
      based Enterococcus (colony-forming units/g) with GI illness (aOR digging = 1.7
      [1.1-2.7]) and diarrhea (2.1 [1.3-3.4]). Associations were not found among
      nonswimmers with sand exposure. CONCLUSIONS: We observed a positive relationship
      between sand-contact activities and enteric illness as a function of
      concentrations of fecal microbial pollution in beach sand.

PMID- 22157309
TI  - Evaluation of respondent-driven sampling.
AB  - BACKGROUND: Respondent-driven sampling is a novel variant of link-tracing
      sampling for estimating the characteristics of hard-to-reach groups, such as HIV
      prevalence in sex workers. Despite its use by leading health organizations, the
      performance of this method in realistic situations is still largely unknown. We
      evaluated respondent-driven sampling by comparing estimates from a respondent
      driven sampling survey with total population data. METHODS: Total population data
      on age, tribe, religion, socioeconomic status, sexual activity, and HIV status
      were available on a population of 2402 male household heads from an open cohort
      in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in
      this population, using current methods of sampling (RDS sample) and statistical
      inference (RDS estimates). Analyses were carried out for the full RDS sample and
      then repeated for the first 250 recruits (small sample). RESULTS: We recruited
      927 household heads. Full and small RDS samples were largely representative of
      the total population, but both samples underrepresented men who were younger, of
      higher socioeconomic status, and with unknown sexual activity and HIV status.
      Respondent-driven sampling statistical inference methods failed to reduce these
      biases. Only 31%-37% (depending on method and sample size) of RDS estimates were
      closer to the true population proportions than the RDS sample proportions. Only
      50%-74% of respondent-driven sampling bootstrap 95% confidence intervals included
      the population proportion. CONCLUSIONS: Respondent-driven sampling produced a
      generally representative sample of this well-connected nonhidden population.
      However, current respondent-driven sampling inference methods failed to reduce
      bias when it occurred. Whether the data required to remove bias and measure
      precision can be collected in a respondent-driven sampling survey is unresolved.
      Respondent-driven sampling should be regarded as a (potentially superior) form of
      convenience sampling method, and caution is required when interpreting findings
      based on the sampling method.

PMID- 22157310
TI  - Commentary:  Respondent-driven Sampling in the Real World.

PMID- 22157311
TI  - Is probabilistic bias analysis approximately Bayesian?
AB  - Case-control studies are particularly susceptible to differential exposure
      misclassification when exposure status is determined following incident case
      status. Probabilistic bias analysis methods have been developed as ways to adjust
      standard effect estimates based on the sensitivity and specificity of exposure
      misclassification. The iterative sampling method advocated in probabilistic bias
      analysis bears a distinct resemblance to a Bayesian adjustment; however, it is
      not identical. Furthermore, without a formal theoretical framework (Bayesian or
      frequentist), the results of a probabilistic bias analysis remain somewhat
      difficult to interpret. We describe, both theoretically and empirically, the
      extent to which probabilistic bias analysis can be viewed as approximately
      Bayesian. Although the differences between probabilistic bias analysis and
      Bayesian approaches to misclassification can be substantial, these situations
      often involve unrealistic prior specifications and are relatively easy to detect.
      Outside of these special cases, probabilistic bias analysis and Bayesian
      approaches to exposure misclassification in case-control studies appear to
      perform equally well.

PMID- 22157312
TI  - On using summary statistics from an external calibration sample to correct for
      covariate measurement error.
AB  - BACKGROUND: Covariate measurement error is common in epidemiologic studies.
      Current methods for correcting measurement error with information from external
      calibration samples are insufficient to provide valid adjusted inferences. We
      consider the problem of estimating the regression of an outcome Y on covariates X
      and Z, where Y and Z are observed, X is unobserved, but a variable W that
      measures X with error is observed. Information about measurement error is
      provided in an external calibration sample where data on X and W (but not Y and
      Z) are recorded. METHODS: We describe a method that uses summary statistics from
      the calibration sample to create multiple imputations of the missing values of X
      in the regression sample, so that the regression coefficients of Y on X and Z and
      associated standard errors can be estimated using simple multiple imputation
      combining rules, yielding valid statistical inferences under the assumption of a
      multivariate normal distribution. RESULTS: The proposed method is shown by
      simulation to provide better inferences than existing methods, namely the naive
      method, classical calibration, and regression calibration, particularly for
      correction for bias and achieving nominal confidence levels. We also illustrate
      our method with an example using linear regression to examine the relation
      between serum reproductive hormone concentrations and bone mineral density loss
      in midlife women in the Michigan Bone Health and Metabolism Study. CONCLUSIONS:
      Existing methods fail to adjust appropriately for bias due to measurement error
      in the regression setting, particularly when measurement error is substantial.
      The proposed method corrects this deficiency.

PMID- 22157313
TI  - Recruiting study participants through Facebook.

PMID- 22157314
TI  - Sensitivity analysis for unmeasured confounding of attributable fraction.

PMID- 22157315
TI  - Hypertension and Alzheimer disease:  is there a link?

PMID- 22157317
TI  - Inverse probability weighting with time-varying confounding and nonpositivity.

PMID- 22157319
TI  - Internalization of adhesion junction proteins and their association with
      recycling endosome marker proteins in rat seminiferous epithelium.
AB  - Tubulobulbar complexes (TBCs) are elaborate cytoskeleton-related structures that
      are formed in association with intercellular junctions in the seminiferous
      epithelium. They consist of a cylindrical double-membrane core composed of the
      plasma membranes of the two attached cells, cuffed by a dendritic network of
      actin filaments. TBCs are proposed to be subcellular machines that internalize
      intercellular junctions during the extensive junction remodeling that occurs
      during spermatogenesis. At the apical sites of attachment between Sertoli cells
      and spermatids, junction disassembly is part of the sperm release mechanism. In
      this study, we used immunological probes to explore junction internalization and
      recycling at apical TBCs in the rat seminiferous epithelium. We demonstrate that
      beta1-integrin and nectin 2 were concentrated at the ends of TBCs and for the
      first time show that the early endosome marker RAB5A was also distinctly
      localized at the ends of TBCs that appear to be the 'bulbar' regions of the
      complexes. Significantly, we also demonstrate that the 'long-loop' recycling
      endosome marker RAB11A was co-distributed with nectin 2 at junctions with early
      spermatids deeper in the epithelium. Our results are consistent with the
      hypothesis that TBCs associated with late spermatids internalize adhesion
      junctions and also indicate that some of the internalized junction proteins may
      be recycled to form junctions with the next generation of spermatids.

PMID- 22157320
TI  - Macrophages:  contributors to allograft dysfunction, repair, or innocent
      bystanders?
AB  - PURPOSE OF REVIEW: Macrophages are members of the innate immune response.
      However, their role in the adaptive immune response is not known. The purpose of
      this review is to highlight our current understanding of macrophage structure and
      function and how they may participate in allograft injury. RECENT FINDINGS:
      Studies in acute kidney injury models identify macrophages as key mediators of
      inflammatory injury, while more recent studies indicate that they may play a
      reparative role, depending on phenotype - M1 or M2 type macrophages. Mregs,
      generated in vitro, appear to have immune suppressive abilities and a unique
      phenotype. In solid-organ transplant, the emphasis of studies has been on acute
      or chronic injury. These data are derived from animal models using depletion of
      macrophages or antagonizing their activation and inflammatory responses. The
      relative contribution of macrophage phenotype in transplantation has not been
      explored. SUMMARY: These studies suggest that macrophages play an injurious role
      in acute cellular allograft rejection, as well as in chronic injury. Infiltration
      of an allograft with macrophages is also associated with worse graft function and
      poor prognosis. Further studies are needed to understand the mechanisms of
      macrophage-mediated injury, explore their potential reparative role, and
      determine if they or their functional products are biomarkers of poor graft
      outcomes.

PMID- 22157322
TI  - Infection control in the multidrug-resistant era: tending the human microbiome.
AB  - Increasing understanding of the normal commensal microorganisms in humans
      suggests that restoring and maintaining the microbiome may provide a key to
      preventing colonization and infection with multidrug-resistant organisms (MDROs).
      Intact communities of commensals can prevent colonization with MDROs through both
      competition for space and resources and the complex immunologic and biochemical
      interactions that have developed between commensal and host over millennia.
      Current antimicrobials, however, exert tremendous collateral damage to the human
      microbiome through overuse and broadening spectrum, which has likely been the
      driving force behind the introduction and proliferation of MDROs. The future
      direction of infection control and anti-infective therapy will likely capitalize
      on an expanding understanding of the protective role of the microbiome by (1)
      developing and using more microbiome-sparing antimicrobial therapy, (2)
      developing techniques to maintain and restore indigenous microbiota, and (3)
      discovering and exploiting host protective mechanisms normally afforded by an
      intact microbiome.

PMID- 22157321
TI  - Rejection and regulation:  a tight balance.
AB  - PURPOSE OF REVIEW: Achieving allograft tolerance is the holy grail of
      transplantation. However, tolerance and rejection are two extreme ends of a scale
      that can be tipped in either direction. We review the novel effector and
      regulatory mechanisms involved and factors that tip the balance in favor of
      rejection or regulation. RECENT FINDINGS: It is increasingly recognized that
      established T-cell phenotypes could change their commitments. New data point to
      the plasticity of Th17 cells in vivo with a reciprocal balance of Th17 cells and
      regulatory T cells (Tregs) driven by the local cytokine environment. Treg-cell
      profiles have been linked to acute and chronic allograft outcomes, and emerging
      data also indicate a novel role of a regulatory B-cell population. Current
      research efforts are looking into factors that tip the balance toward allograft
      tolerance by targeting cytokines, novel costimulatory pathways such as T-cell
      immunoglobulin mucin molecules, and components of innate immunity, particularly
      dendritic cells. SUMMARY: The balance of effector and regulatory mechanisms
      contributing to allograft outcome is very complex. It is likely that targeting
      multiple pathways will be required to achieve tolerance. Further studies are
      warranted to define this balance and identify optimal combination of therapeutic
      interventions.

PMID- 22157323
TI  - Impaired CD4 T-cell count response to combined antiretroviral therapy in
      antiretroviral-naive HIV-infected patients presenting with tuberculosis as AIDS
      defining condition.
AB  - BACKGROUND: The impact of human immunodeficiency virus (HIV)-associated
      tuberculosis on CD4 T-cell count response to combined antiretroviral therapy
      (cART) is poorly investigated. METHODS: A collaborative analysis including HIV
      infected patients prospectively enrolled in 4 Italian clinical cohorts was
      conducted. Patients were grouped according to Centers for Disease Control and
      Prevention stage at the start of cART as having tuberculosis, having AIDS but not
      tuberculosis (nontuberculosis AIDS), and not having AIDS (AIDS free). Time to CD4
      T-cell count of at least 100, 200, and 300 cells/MUL above pre-cART levels and to
      CD4 T-cell count of >500 cells/MUL were major end points. Survival analysis with
      time-fixed and time-dependent covariates was used. RESULTS: A total of 6528
      patients were eligible; 125 patients (2%) had tuberculosis, 1062 (16%) had
      nontuberculosis AIDS, and 5341 (82%) were AIDS free. Patients with tuberculosis
      had a significantly reduced chance of CD4 T-cell count increase compared with
      AIDS-free patients as well as those with nontuberculosis AIDS, regardless of the
      primary outcome considered for a given value of confounders measured at baseline
      (eg, for >200 cells/MUL above baseline; relative hazard, 0.71; P = .02), although
      it was no longer significant after further adjustment for current level of viral
      load suppression (relative hazard, 0.80; P = .11). There was a trend for reduced
      virological response in patients treated concomitantly for tuberculosis and HIV
      infection compared with those who were treated separately in time (P = .09).
      CONCLUSIONS: HIV-infected patients starting cART with a tuberculosis diagnosis
      showed an impaired immune recovery to cART compared with AIDS-free patients and
      those with nontuberculosis AIDS. It seems to be driven mainly by a delay in
      achieving viral suppression. Whether this may be due to interactions between
      antituberculosis drugs and antiretrovirals needs to be investigated.

PMID- 22157325
TI  - Use of aliskiren in a 'real-life' model of hypertension management:  analysis of
      national Web-based drug-monitoring system in Italy.
AB  - INTRODUCTION: In Italy, prescriptions of the direct renin inhibitor aliskiren
      (aliskiren) to high-risk hypertensive patients must be electronically filled by
      specialized physicians only when at least two antihypertensive drug classes
      (independently of the dosages), fails to normalize blood pressure (BP) levels.
      AIM: To analyze the effects of the addition of aliskiren 150-300 mg daily to
      antihypertensive therapy in a population of high cardiovascular risk hypertensive
      patients with uncontrolled BP levels. METHODS: Clinical data were derived from
      patients included in the national Web-based drug-monitoring system. Follow-up
      visits were required for measuring BP levels, and collecting data on drug safety
      and tolerability. RESULTS: Between March 2009 and February 2010, aliskiren was
      prescribed by 6464 specialized physicians to 11 511 treated, uncontrolled
      hypertensive patients (47.6% women, aged 68.0 +/- 11.1 years, BMI 28.4 +/- 4.9
      kg/m) with organ damage or comorbidities. During 6-month observation, only a few
      drug-related side-effects were reported (n = 33). At the entry and 1-month follow
      up visits (n = 8197; 70.6%), BP levels were 158.9 +/- 16.8 and 142.1 +/- 15.2
      mmHg for SBP and 90.8 +/- 9.6 and 83.1 +/- 8.5 mmHg for DBP, respectively. At 6
      month (n = 4907; 42.3%), SBP and DBP levels were 137.9 +/- 13.9 and 81.3 +/- 8.0
      mmHg, respectively. A consistent reduction in the use of all classes of
      concomitant antihypertensive drugs was recorded. CONCLUSION: Although data
      derived from national registries need to be interpreted with caution, the Italian
      Web-based drug-monitoring system provided information on 'real-life' use of
      aliskiren in hypertension. In this uncontrolled, high-risk treated hypertensive
      population, SBP and DBP levels recorded during treatment with aliskiren were
      consistently lower than those recorded at entry visits in a context of a very low
      rate of reported side-effects.

PMID- 22157326
TI  - Longitudinal changes in blood pressure during weight loss and regain of weight in
      obese boys and girls.
AB  - OBJECTIVE: To investigate blood pressure (BP) in relation to changes in body mass
      index (BMI) in obese children during weight loss and subsequent weight regain.
      DESIGN: A longitudinal study of obese boys and girls investigated through a 12
      week weight loss intervention with follow-up investigations spanning 28 months.
      Results shown are from baseline; day 14, 33, and 82 during weight loss; and at
      months 10, 16 and 28 during follow-up. PATIENTS: One hundred and fifteen obese
      children, 53 boys and 62 girls (8-15 years) with a median BMI standard deviation
      score (SDS) at baseline of 2.78 in boys, and 2.70 in girls. Ninety children
      completed the weight loss programme and 68 children entered the follow-up
      programme. METHODS: Height, weight, systolic blood pressure (SBP), and diastolic
      BP (DBP) were recorded and analysed using a general linear mixed model. RESULTS:
      Fifty-one percent of the obese children were pre or hypertensive at baseline.
      Both DBP and SBP declined significantly with weight loss, but a divergent
      response was found in the timing of the rebound in hypertension during the weight
      regain phase, that is DBP increased during weight regain, whereas SBP remained
      lower than baseline during 28 months of continuous weight regain. CONCLUSION: The
      effect of weight reduction upon obesity-associated hypertension is noticeable and
      suggests the importance of an intensified childhood obesity treatment strategy in
      order to reduce the burden of future cardiovascular disease.

PMID- 22157324
TI  - Systemic antibiotic therapy for chronic osteomyelitis in adults.
AB  - The standard recommendation for treating chronic osteomyelitis is 6 weeks of
      parenteral antibiotic therapy. However, oral antibiotics are available that
      achieve adequate levels in bone, and there are now more published studies of oral
      than parenteral antibiotic therapy for patients with chronic osteomyelitis. Oral
      and parenteral therapies achieve similar cure rates; however, oral therapy avoids
      risks associated with intravenous catheters and is generally less expensive,
      making it a reasonable choice for osteomyelitis caused by susceptible organisms.
      Addition of adjunctive rifampin to other antibiotics may improve cure rates. The
      optimal duration of therapy for chronic osteomyelitis remains uncertain. There is
      no evidence that antibiotic therapy for >4-6 weeks improves outcomes compared
      with shorter regimens. In view of concerns about encouraging antibiotic
      resistance to unnecessarily prolonged treatment, defining the optimal route and
      duration of antibiotic therapy and the role of surgical debridement in treating
      chronic osteomyelitis are important, unmet needs.

PMID- 22157327
TI  - Innate and adaptive immune responses in chronic hepatitis B virus infections:
      towards restoration of immune control of viral infection.
AB  - Knowledge of the immunological events necessary to control hepatitis B virus
      (HBV) infection has accelerated in recent years, but their translation towards
      therapeutic strategies able to achieve a durable HBV suppression has been
      challenging. The scenario of how HBV deals with the host immunity is presented
      and used to discuss how the immune response can be harnessed to potentially
      achieve infection control.

PMID- 22157328
TI  - Cathepsin B promotes the progression of pancreatic ductal adenocarcinoma in mice.
AB  - OBJECTIVE: The lysosomal protease cathepsin B is upregulated in human pancreatic
      ductal adenocarcinoma (PDA) and represents a potential therapeutic target. Loss
      of cathepsin B delays tumour progression in mouse models of islet, mammary and
      intestinal carcinoma and decreases invasion and metastasis. This study examines
      the role of cathepsin B in the initiation, progression and metastasis of PDA.
      METHODS: Cathepsin B germline knockout mice were crossed with animals expressing
      an endogenous Kras(G12D) allele in the pancreas, and mice were aged to evaluate
      the role of cathepsin B in pancreatic intraepithelial neoplasia (PanIN). A
      survival study was also performed with mice carrying an additional heterozygous
      conditional Trp53(R172H) allele. Cell lines derived from tumours were used to
      investigate the role of cathepsin B in vitro, and subcutaneous allografts
      investigated the cell autonomous and non-cell autonomous roles of cathepsin B in
      pancreatic cancer. RESULTS: Constitutive cathepsin B loss resulted in delayed
      progression of both PanIN and PDA and a significant survival advantage in mice.
      Cathepsin B-deficient PDA cells and PanIN showed decreased proliferation and
      mitogen-activated protein (MAP) kinase signalling. The reconstitution of
      deficient cells with cathepsin B reversed these findings, which correlated with
      decreased levels of the active forms of the related protease cathepsin L.
      Conversely, acute ablation of cathepsin L activated the MAP kinase cascade in PDA
      cells. CONCLUSIONS: These results confirm that cathepsin B plays an important
      cell autonomous role in the progression of PDA and suggest that the regulation of
      cathepsin L by cathepsin B may be a means of stimulating cell proliferation in
      neoplasia.

PMID- 22157329
TI  - A placebo-controlled trial of acotiamide for meal-related symptoms of functional
      dyspepsia.
AB  - OBJECTIVE: To determine the efficacy of acotiamide, an acetylcholinesterase
      inhibitor, in patients with functional dyspepsia (FD) in a 4-week trial. METHODS:
      A multicentre, randomised, placebo-controlled, parallel-group, phase III trial
      was carried out, in which patients with FD received 100 mg of acotiamide or
      placebo three times a day for 4 weeks, with 4 weeks post-treatment follow-up. The
      primary efficacy end points were global assessment of overall treatment efficacy
      (OTE) and elimination rate of all three meal-related symptoms (postprandial
      fullness, upper abdominal bloating and early satiation), as derived from daily
      diaries. Secondary efficacy end points were individual symptom scores and quality
      of life. Adverse events were monitored. RESULTS: 52.2% of those receiving
      acotiamide and 34.8% in the placebo group (p<0.001) were classified as responders
      according to a global assessment of OTE. Over 4 weeks, the elimination rate for
      all three meal-related symptoms was 15.3% among patients receiving acotiamide
      compared with 9.0% in the placebo group (p=0.004). The significant benefit of
      acotiamide over placebo in OTE and elimination rate was maintained during the 4
      week post-treatment follow-up. All other secondary efficacy end points, including
      quality of life, were significantly improved with 100 mg of acotiamide as
      compared with placebo. The number needed to treat was 6 for OTE and 16 for
      symptom elimination rate. The incidence of adverse events was similar between the
      acotiamide group and placebo group and no significant cardiovascular effects due
      to treatment were seen. CONCLUSIONS: Over 4 weeks, acotiamide significantly
      improved symptom severity and eliminated meal-related symptoms in patients with
      FD. TRIAL REGISTRATION NUMBER: http://ClinicalTrials.gov number, NCT00761358.

PMID- 22157331
TI  - Inflammatory bowel disease therapies and cancer risk: where are we and where are
      we going?

PMID- 22157330
TI  - Glutathione peroxidase 7 protects against oxidative DNA damage in oesophageal
      cells.
AB  - OBJECTIVE: Exposure of the oesophageal mucosa to gastric acid and bile acids
      leads to the accumulation of reactive oxygen species (ROS), a known risk factor
      for Barrett's oesophagus and progression to oesophageal adenocarcinoma (OAC).
      This study investigated the functions of glutathione peroxidase 7 (GPX7),
      frequently silenced in OAC, and its capacity in regulating ROS and its associated
      oxidative DNA damage. DESIGN: Using in-vitro cell models, experiments were
      performed that included glutathione peroxidase (GPX) activity, Amplex UltraRed,
      CM-H(2)DCFDA, Annexin V, 8-oxoguanine, phospho-H2A.X, quantitative real-time PCR
      and western blot assays. RESULTS: Enzymatic assays demonstrated limited GPX
      activity of the recombinant GPX7 protein. GPX7 exhibited a strong capacity to
      neutralise hydrogen peroxide (H(2)O(2)) independent of glutathione.
      Reconstitution of GPX7 expression in immortalised Barrett's oesophagus cells, BAR
      T and CP-A led to resistance to H(2)O(2)-induced oxidative stress. Following
      exposure to acidic bile acids cocktail (pH4), these GPX7-expressing cells
      demonstrated lower levels of H(2)O(2), intracellular ROS, oxidative DNA damage
      and double-strand breaks, compared with controls (p<0.01). In addition, these
      cells demonstrated lower levels of ROS signalling, indicated by reduced phospho
      JNK (Thr183/Tyr185) and phospho-p38 (Thr180/Tyr182), and demonstrated lower
      levels of apoptosis following the exposure to acidic bile acids or H(2)O(2)
      induced oxidative stress. The knockdown of endogenous GPX7 in immortalised
      oesophageal squamous epithelial cells (HET1A) confirmed the protective functions
      of GPX7 against pH4 bile acids by showing an increase in the levels of H(2)O(2),
      intracellular ROS, oxidative DNA damage, double-strand breaks, apoptosis, and ROS
      dependent signalling (p<0.01). CONCLUSION: The dysfunction of GPX7 in oesophageal
      cells increases the levels of ROS and oxidative DNA damage, which are common risk
      factors for Barrett's oesophagus and OAC.

PMID- 22157332
TI  - Studies on factors predicting GORD response to proton-pump inhibitors: NERD
      subpopulations need to be analysed separately.

PMID- 22157334
TI  - Be careful what you wish for.

PMID- 22157333
TI  - Lymphocytic oesophagitis: clinicopathological aspects of an emerging condition.
AB  - OBJECTIVE: Lymphocytic oesophagitis (LyE) has been reported in small series, but
      no consistent clinical correlations have emerged. The authors sought to determine
      the prevalence of LyE in a large population and define demographic, endoscopic
      and clinical findings associated with this condition. DESIGN: In a pilot study,
      the authors established and disseminated criteria for the histopathological
      diagnosis of LyE to a group of gastrointestinal pathologists. Eighteen months
      later the authors reviewed cases with this diagnosis, collected demographic,
      clinical and endoscopic data, and compared them with patients with either
      eosinophilic oesophagitis (EoE) or normal oesophageal biopsies. The authors also
      determined the density of oesophageal lymphocytes in normal controls and in
      adults with established Crohn's disease. RESULTS: There were 129,252 unique
      PATIENTS: 40,665 had normal mucosa (median age 55 years; 32% men); 3745 had EoE
      (median age 43 years; 66% men). A diagnosis of LyE was made in 119 patients
      (median age 63 years, 40% men). Dysphagia was as common in these patients as in
      those with EoE (53% vs 63%; ns); gastro-oesophageal reflux disease -the most
      common complaint in patients with normal biopsies (37%)-was low in both the LyE
      and the EoE groups (18% vs 19%, ns). EoE was suspected in one-third of the
      patients. CONCLUSION: LyE was detected in ~0.1% of patients with oesophageal
      biopsies. The clinical and endoscopic characteristics of LyE and EoE overlap
      considerably; however, LyE affects predominantly older women. Although the
      precise clinical significance of oesophageal lymphocytic infiltrates remain to be
      defined, their association with dysphagia and possibly motility disorders
      warrants further investigations.

PMID- 22157335
TI  - Pro/Con: should children visit patients in an intensive care unit (ICU)?

PMID- 22157338
TI  - Understanding hydatidiform mole.
AB  - Hydatidiform mole (often referred to as molar pregnancy) is the most common
      disorder in a category of pathologies known as Gestational Trophoblastic Diseases
      that are associated with abnormal fertilization in pregnancy. Current practices
      in screening and monitoring during early pregnancy allow for better
      identification of hydatidiform mole, sometimes prior to the onset of significant
      symptoms.Once a diagnosis is established, a thorough physical examination and
      laboratory testing are necessary. Initial treatment includes uterine evacuation.
      Serial monitoring of serum human chorionic gonadotropin levels is warranted until
      levels become nondetectable and continues for another 6 months. Reliable
      contraception is necessary until it has been determined that no trophoblastic
      tissue persists.Pregnancy is usually a joyful time, with maternal attachment to
      the developing fetus beginning early in the pregnancy. The woman who experiences
      hydatiform mole, however, must face the inability to maintain this pregnancy, the
      possible health consequences of the mole, and then be allowed the time to grieve.
      Nurses can be the first-line in providing compassionate, empathetic care for
      women in these circumstances.

PMID- 22157339
TI  - Interruptions to breastfeeding Dyads in an DRP Unit.
AB  - PURPOSE: The critical period for establishing breastfeeding (BF) is during the
      first days after birth. However, some routine maternity unit care practices may
      be experienced as interruptions interfering with BF opportunities and
      satisfaction. Therefore, we wanted to describe the frequency and duration of
      interruptions; amount of time alone; number, length, success of, and satisfaction
      with BF sessions; and maternal perceptions of the influence of interruptions on
      BF experiences in an LDR unit on postpartum day 1 (PD1). STUDY DESIGN AND
      METHODS: For 12 hours on PD1 we continuously observed the door to the rooms of 30
      mother-newborn dyads in a community hospital birthing center. We recorded
      duration of visit by each person entering the room. Length of BF and maternal
      perception of success and satisfaction were measured after each feeding and at
      the end of the day using visual analog scales. RESULTS: One thousand five hundred
      ninety-three interruptions (53 +/- 13.4/dyad, range 27-85) and 703 episodes of
      time alone (23 +/- 5.5/dyad, range 11-32) occurred across 360 hours of
      observation. Duration of interruptions and time alone were 18.5 +/- 34.5 and 15.4
      +/- 17.3 minutes, respectively. However, median duration of interruptions was 5
      minutes and of time alone 10 minutes. One hundred thirty-eight BF sessions were
      recorded (2-9 sessions) and lasted 25 +/-14.98 minutes. Perceived maternal
      success and satisfaction with BFs were moderate, and interruptions only
      marginally interfered with BF opportunities. CLINICAL IMPLICATIONS: Too many
      interruptions occur and mothers perceive them as interfering with BF. Therefore,
      interruptions need to be minimized.

PMID- 22157340
TI  - Teaching guatemala midwives about postpartum hemorrhage.
AB  - PURPOSE: To evaluate the effect of a culturally sensitive teaching unit on
      traditional midwives' knowledge of nursing interventions to prevent and treat
      postpartum hemorrhage (PPH). METHODS: Sixteen midwives participated in a 1-day
      training program at a Refuge International Health Clinic in the remote town of
      Sarstun, Guatemala. The quasi experimental study used a one-group, pretest
      posttest design. Researchers used a PPH Behavioral Checklist from the American
      College of Nurse Midwives (ACNM) to assess and compare knowledge of PPH
      interventions before and after the PPH teaching. RESULTS: The final analysis
      included 13 traditional midwives as the subjects. The culturally sensitive
      teaching improved traditional midwives' knowledge and skills about nursing
      interventions to manage PPH (pretest M = 1.385/8, posttest M = 4.846/8).
      CONCLUSIONS: Results of this pilot project suggest a culturally sensitive oral
      teaching in the primary language of the participants positively affects
      traditional midwives' knowledge and skills to manage PPH. Future training should
      be presented in a similar format to meet the needs of illiterate audiences in
      resource-poor settings.

PMID- 22157341
TI  - Eating disorders and pregnancy: supporting the anorexic or bulimic expectant
      mother.
AB  - Eating disorders have been on the rise since the 1980s. For a woman previously
      treated for an eating disorder such as anorexia or bulimia, a pregnancy may
      exacerbate prior symptoms. Women with an eating disorder may also be embarrassed
      by or reluctant to reveal prior or current symptoms to healthcare providers. This
      article presents a case study of an expectant new mother with a history of
      anorexia. The information will help nurses become more alert to predisposing
      factors that may indicate a potential problem with an eating disorder, and
      provide practical ways to help these women cope with their anxiety about their
      changing bodies. As a result, nurses can help these women maintain a healthy
      pregnancy with a good neonatal outcome.

PMID- 22157342
TI  - Weight-management information needs of postpartum women.
AB  - PURPOSE: To describe the weight loss information-seeking behaviors of postpartum
      women. STUDY DESIGN AND METHODS: The study is part of a larger longitudinal
      descriptive study of factors associated with women's self-management of their
      gestational weight loss after birth. Participants answered questions about weight
      loss information they planned to access, had received, wished they had received,
      and desired sources of information. A total of 250 women were enrolled during the
      postpartum hospital stay; 179 completed a 4-month follow-up. RESULTS: A large
      portion of the sample (53.3% of normal weight women, 79% of overweight women, and
      81.4% obese women) identified plans to seek weight loss information, yet nearly
      85% received no information from healthcare providers by 4 months postpartum. The
      most frequently reported desired information topics fell under the category of
      specific strategies to lose weight. The majority of women in the sample had
      access to online health information from home, work, or a library; however, more
      White women had this access than did Black or Hispanic women. CLINICAL
      IMPLICATIONS: Postpartum hospital nurses are in a unique position to provide high
      quality information with strategies for managing postpartum loss of gestational
      weight. Provision of high-quality online or print information can provide the
      foundation for successful weight-management support for prevention of gestational
      weight retention and long-term maintenance of a healthy weight.

PMID- 22157343
TI  - Embracing the surgeon general's call to action to support breastfeeding.

PMID- 22157344
TI  - Social networking safety for children and adolescents.

PMID- 22157345
TI  - Breaking the cycle of poverty:  global girlfriends.

PMID- 22157347
TI  - Just say no.

PMID- 22157348
TI  - Metabolic conditioning to attenuate the adverse effects of perioperative fasting
      and improve patient outcomes.
AB  - PURPOSE OF REVIEW: To review recent articles, published between October 2009 and
      September 2011, that examined the adverse metabolic consequences of perioperative
      fasting and interventions that may be utilized to minimize these effects. RECENT
      FINDINGS: Fasting induces metabolic stress and insulin resistance consequent upon
      effects on cellular mitochondria, gene and protein expression. Development of
      perioperative insulin resistance leads to increased postoperative morbidity and
      mortality. Preoperative carbohydrate loading attenuates insulin resistance via
      effects on cellular gene and protein expression, but its effects on clinical
      outcomes remain unclear. Perioperative arginine-supplemented diets were shown to
      be associated with significant reductions in infectious complications and length
      of hospital stay in patients undergoing elective surgery. Perioperative metabolic
      conditioning using glutamine and L-carnitine may be used to modulate insulin
      sensitivity but further studies need to determine whether these interventions
      result in clinical benefit. Finally, energy and protein provision to critically
      ill patients remains inadequate and is hampered by a number of factors including
      reliance on inaccurate means of estimating energy expenditure and enteral feed
      tolerance, conflicting data on the effects of energy deficit on clinical
      outcomes, and poor methodological quality of studies of perioperative nutritional
      interventions. SUMMARY: Numerous perioperative interventions are available, which
      if utilized should help attenuate the adverse effects of perioperative fasting
      and lead to improved patient outcomes.

PMID- 22157349
TI  - Autism, cognition, and parent counseling--Part 2.
AB  - As the incidence of autism has risen, many neurodevelopmental pediatricians have
      been omitting a consideration of cognitive level in their evaluation of children,
      and in communicating with parents. This is a disservice to families, who should
      be given pertinent information, both in verbal and written forms, about their
      child and the prognosis. A template is presented for a letter that can be
      provided to parents, highlighting the basic information they need after a
      diagnosis has been made.

PMID- 22157350
TI  - Changes over time in reducing developmental and behavioral comorbidities of
      asthma in children.
AB  - OBJECTIVE: The purpose of this study was to determine (1) the progress that has
      been made in reducing the prevalence of asthma and/or reducing its severity over
      the past decade and (2) the progress that has been made in reducing the
      developmental and behavioral comorbidities of asthma during this period. METHODS:
      Rates of asthma, asthma severity, and developmental and behavioral problems among
      children with asthma were compared between the 2003 and 2007 National Surveys of
      Children's Health. RESULTS: Asthma rates remained stable between the 2 surveys,
      but there was a shift from moderate to mild and, to a lesser extent, severe
      asthma. Comorbid rates of developmental and behavioral problems were about twice
      as high among children with asthma compared with those without asthma. All
      problems increased for both groups between the surveys but at a significantly
      greater pace for repeated grades among children with asthma. CONCLUSIONS:
      Children with asthma continue to have high rates of comorbid developmental and
      behavioral problems. Over the past decade, these problems are becoming more, not
      less frequent. Primary and asthma specialty caregivers should be attuned to these
      comorbidities and implement methods to screen for, assess, and remediate these
      problems as early as possible.

PMID- 22157351
TI  - Factors associated with driving in teens with autism spectrum disorders.
AB  - OBJECTIVE: To compare the characteristics of driving and nondriving teens and
      explore the driving outcomes for teens with higher functioning autism spectrum
      disorders. METHODS: Parents of teens aged 15 to 18 years with a parent-reported
      diagnosis of an autism spectrum disorder enrolled in Interactive Autism Network,
      an online research registry, were eligible for this cross-sectional study. An
      online survey was used for data collection. RESULTS: A total of 297 parents
      completed the survey. Sixty-three percent of teens currently drive or plan to
      drive. Twenty-nine percent of the teens who are age-eligible to drive currently
      drive. Compared with age-eligible but nondriving teens, a greater proportion of
      driving teens were in full-time regular education (p < .005), planned to attend
      college (p < .001), and held a paid job (p = .008). A greater proportion of
      parents of driving teens had taught >=1 teen to drive previously (p < .001).
      There were no differences in gender, autism subtype, attention
      deficit/hyperactivity disorder diagnosis, parental age or education, or access to
      public transportation. Driving predictors included individualized education plans
      with driving goals, indicators of functional status (classroom placement, college
      aspiration, and job experience), and parent experience with teaching teens to
      drive. Twelve percent of teens received driving citations, and 12% of teens had
      been involved in a motor vehicle crash. CONCLUSIONS: Although a significant
      proportion of teens with higher functioning autism spectrum disorders were
      driving or learning to drive, the fact that most driving teens' individualized
      education plans did not include driving goals suggests an area of opportunity for
      improvement in transition planning. Driving teens were more frequently in regular
      education settings with college aspirations, which could help schools identify
      potential drivers.

PMID- 22157352
TI  - Quality of life of adolescents raised from birth by lesbian mothers: the US
      National Longitudinal Family Study.
AB  - OBJECTIVE: To compare the quality of life (QoL), a measure of psychological well
      being, of adolescents reared in lesbian-mother families with that of a matched
      comparison group of adolescents with heterosexual parents. The adolescents in the
      comparison group were derived from a representative sample of adolescents in
      Washington state. The second aim of the study was to assess among teens with
      lesbian mothers whether donor status, maternal relationship continuity, and self
      reported stigmatization are associated with QoL. METHODS: In 1986, prospective
      lesbian mothers were recruited in Boston, Washington, DC, and San Francisco.
      Currently, 93% of the National Longitudinal Lesbian Family Study (NLLFS) families
      are still participating in the study. This report is based on an online
      questionnaire completed by 78 NLLFS adolescent offspring-39 girls and 39 boys.
      Six items of the Youth Quality of Life Instrument were used to assess QoL. Also,
      the NLLFS adolescents were asked whether they had experienced stigmatization, and
      if so, to describe these experiences (e.g., teasing and ridicule). Mothers were
      queried about donor status and maternal relationship continuity. RESULTS: The
      results revealed that the NLLFS adolescents rated their QoL comparably to their
      counterparts in heterosexual-parent families. Donor status, maternal relationship
      continuity, and experienced stigmatization were not related to QoL. CONCLUSION:
      Adolescent offspring in planned lesbian families do not show differences in QoL
      when compared with a matched group of adolescents reared in heterosexual
      families. By investigating QoL, this study provides insight into positive aspects
      of mental health of adolescents with lesbian mothers.

PMID- 22157353
TI  - Cytotoxicity evaluation of oxidized single-walled carbon nanotubes and graphene
      oxide on human hepatoma HepG2 cells: an iTRAQ-coupled 2D LC-MS/MS proteome
      analysis.
AB  - Because of their attractive chemical and physical properties, graphitic
      nanomaterials and their derivatives have gained tremendous interest for
      applications in electronics, materials, and biomedical areas. However, few
      detailed studies have been performed to evaluate the potential cytotoxicity of
      these nanomaterials on living systems at the molecular level. In the present
      study, our group exploited the isobaric tagged relative and absolute
      quantification (iTRAQ)-coupled two-dimensional liquid chromatography-tandem mass
      spectrometry (2D LC-MS/MS) approach with the purpose of characterizing the
      cellular functions in response to these nanomaterials at the proteome level.
      Specifically, the human hepatoma HepG2 cells were selected as the in vitro model
      to study the potential cytotoxicity of oxidized single-walled carbon nanotubes
      (SWCNTs) and graphene oxide (GO) on the vital organ of liver. Overall, 30
      differentially expressed proteins involved in metabolic pathway, redox
      regulation, cytoskeleton formation, and cell growth were identified. Based on the
      protein profile, we found oxidized SWCNTs induced oxidative stress and interfered
      with intracellular metabolic routes, protein synthesis, and cytoskeletal systems.
      Further functional assays confirmed that oxidized SWCNTs triggered elevated level
      of reactive oxygen species (ROS), perturbed the cell cycle, and resulted in a
      significant increase in the proportion of apoptotic cells. However, only moderate
      variation of protein levels for the cells treated with GO was observed and
      functional assays further confirmed that GO was less cytotoxic in comparison to
      oxidized SWCNTs. These finding suggested that GO was more biocompatible and could
      be a promising candidate for bio-related applications.

PMID- 22157355
TI  - Application of data mining and visualization techniques for the prediction of
      drug-induced nausea in man.
AB  - The therapeutic value of many drugs can be limited by gastrointestinal (GI)
      adverse effects such as nausea and vomiting. Nausea is a subjective human
      sensation, hence little is known about preclinical biomarkers that may accurately
      and effectively predict its presence in man. The aim of this analysis was to use
      informatics and data-mining tools to identify plausible preclinical GI effects
      that may be associated with nausea and that could be of potential use in its
      prediction. A total of 86 marketed drugs were used in this analysis, and the main
      outcome was a confirmation that nausogenic and non-nausogenic drugs can be
      clearly separated based on their preclinical GI observations. Specifically,
      combinations of common preclinical GI effects (vomiting, diarrhea, and salivary
      hypersecretion) proved to be strong predictors. The model was subsequently
      validated with a subset of 20 blinded proprietary small molecules and
      successfully predicted clinical outcome in 90% of cases. This investigation
      demonstrated the feasibility of data-mining approaches to facilitate discovery of
      novel, plausible associations that can be used to understand drug-induced adverse
      effects.

PMID- 22157354
TI  - Formation of hydroxymethyl DNA adducts in rats orally exposed to stable isotope
      labeled methanol.
AB  - Methanol is a large volume industrial chemical and widely used solvent and fuel
      additive. Methanol's well known toxicity and use in a wide spectrum of
      applications has raised long-standing environmental issues over its safety,
      including its carcinogenicity. Methanol has not been listed as a carcinogen by
      any regulatory agency; however, there are debates about its carcinogenic
      potential. Formaldehyde, a metabolite of methanol, has been proposed to be
      responsible for the carcinogenesis of methanol. Formaldehyde is a known
      carcinogen and actively targets DNA and protein, causing diverse DNA and protein
      damage. However, formaldehyde-induced DNA adducts arising from the metabolism of
      methanol have not been reported previously, largely due to the absence of
      suitable DNA biomarkers and the inability to differentiate what was due to
      methanol compared with the substantial background of endogenous formaldehyde.
      Recently, we developed a unique approach combining highly sensitive liquid
      chromatography-mass spectrometry methods and exposure to stable isotope labeled
      chemicals to simultaneously quantify formaldehyde-specific endogenous and
      exogenous DNA adducts. In this study, rats were exposed daily to 500 or 2000
      mg/kg [13CD4]-methanol by gavage for 5 days. Our data demonstrate that labeled
      formaldehyde arising from [13CD4]-methanol induced hydroxymethyl DNA adducts in
      multiple tissues in a dose-dependent manner. The results also demonstrated that
      the number of exogenous DNA adducts was lower than the number of endogenous
      hydroxymethyl DNA adducts in all tissues of rats administered 500 mg/kg per day
      for 5 days, a lethal dose to humans, even after incorporating an average factor
      of 4 for reduced metabolism due to isotope effects of deuterium-labeled methanol
      into account.

PMID- 22157356
TI  - Risk stratification in stable coronary artery disease:  superiority of N-terminal
      pro B-type natriuretic peptide over high-sensitivity C-reactive protein, gamma
      glutamyl transferase, and traditional risk factors.
AB  - OBJECTIVE: The aim of the study was to compare N-terminal pro B-type natriuretic
      peptide (NT-proBNP), high-sensitivity C-reactive protein, and gamma-glutamyl
      transferase (gamma-GT) with traditional risk markers for estimating prognosis in
      patients with stable coronary artery disease (CAD). MATERIALS AND METHODS:
      Evaluation of mortality and a combined clinical endpoint (mortality, need for
      coronary revascularization, myocardial infarction, hospitalization for cardiac
      causes, or stroke) during an average 3.2-year follow-up in 394 consecutive
      patients (73% male patients, age: 67+/-9 years) with angiographically proven
      stable CAD. RESULTS: Univariate Kaplan-Meier survival rate analysis showed that
      traditional risk markers, apart from impaired renal function, three-vessel CAD,
      and a reduced left ventricular function at the time of coronary angiography, were
      not of prognostic relevance for prediction of outcome. NT-proBNP, high
      sensitivity C-reactive protein, and gamma-glutamyl transferase were significant
      predictors of mortality; however, only NT-proBNP was a significant predictor of
      the combined endpoint. In age-adjusted and sex-adjusted multivariate Cox
      regression analysis, NT-proBNP was the strongest independent predictor of the
      combined endpoint (odds ratio 2.92, 95% confidence interval: 1.72-4.94, first vs.
      third tertile). All three laboratory parameters remained independent risk markers
      for mortality in multivariate analysis. NT-proBNP, however, revealed the highest
      odds ratio (5.23, 95% confidence interval: 1.17-23.23, first vs. third tertile).
      Concentrations greater than 356 ng/l predicted mortality with a sensitivity of
      70%, a specificity of 71%, a positive likelihood ratio of 2.4, and a negative
      likelihood ratio of 0.42. CONCLUSION: In comparison with other tested novel
      biomarkers and traditional risk markers, NT-proBNP was the most predictive
      prognostic marker in multivariate analysis in patients with stable CAD.

PMID- 22157357
TI  - Incidence, prognosis, and factors associated with cardiac arrest in patients
      hospitalized with acute coronary syndromes (the Global Registry of Acute Coronary
      Events Registry).
AB  - OBJECTIVES: Contemporary data are lacking with respect to the incidence rates of,
      factors associated with, and impact of cardiac arrest from ventricular
      fibrillation or tachycardia (VF-CA) on hospital survival in patients admitted
      with an acute coronary syndrome (ACS). The objectives of this multinational study
      were to characterize trends in the magnitude of in-hospital VF-CA complicating an
      ACS and to describe its impact over time on hospital prognosis. METHODS: In 59
      161 patients enrolled in the Global Registry of Acute Coronary Events Study
      between 2000 and 2007, we determined the incidence, prognosis, and factors
      associated with VF-CA. RESULTS: Overall, 3618 patients (6.2%) developed VF-CA
      during their hospitalization for an ACS. Incidence rates of VF-CA declined over
      time. Patients who experienced VF-CA were on average older and had a greater
      burden of cardiovascular disease, yet were less likely to receive evidence-based
      cardiac therapies than patients in whom VF-CA did not occur. Hospital death rates
      were 55.3% and 1.5% in patients with and without VF-CA, respectively. There was a
      greater than 50% decline in the hospital death rates associated with VF-CA during
      the years under study. Patients with a VF-CA occurring after 48 h were at
      especially high risk for dying during hospitalization (82.8%). CONCLUSION:
      Despite reductions in the magnitude of, and short-term mortality from, VF-CA, VF
      CA continues to exert an adverse effect on survival among patients hospitalized
      with an ACS. Opportunities exist to improve the identification and treatment of
      ACS patients at risk for VF-CA to reduce the incidence of, and mortality from,
      this serious arrhythmic disturbance.

PMID- 22157358
TI  - Body surface area is a predictor of coronary artery calcium, whereas body mass
      index is not.
AB  - INTRODUCTION: We sought to establish whether elevated BMI and body surface area
      (BSA), two measures of obesity, are predictors of coronary artery calcium (CAC).
      METHODS: We retrospectively analyzed 3172 consecutive patients who underwent
      calcium scoring at our center. We applied a multiple logistic regression model to
      estimate the independent association between BMI of at least 25 kg/m(2) and
      incidence of CAC with adjustment for covariates. We carried out the same analysis
      to find out if there is an independent association between BSA of at least 1.71
      m(2) (commonly used definition for abnormally elevated BSA) and incidence of CAC.
      We also performed a sex subanalysis based on BMI and BSA. RESULTS: There were
      2105 patients in the cohort with BMI of at least 25 kg/m(2) compared with 1067
      patients with BMI of less than 25 kg/m(2). After adjustment for covariates, a
      significant association was not found between increased BMI and incidence of CAC.
      In addition, no significant findings were found in the sex subanalysis. A total
      of 2760 patients had a BSA of at least 1.71 m(2) compared with 412 patients with
      BSA of less than 1.71 m(2). After adjustment for covariates, a significant
      association (odds ratio 2.08, 95% confidence interval 1.16-3.73, P=0.014) was
      found between elevated BSA and CAC incidence. There were 89 men with BSA of at
      least 1.9 m(2) and 2248 with BSA of at least 1.9 m(2). After adjustment for
      covariates, the logistic regression model showed a significant association (odds
      ratio 2.24, 95% confidence interval 1.19-4.21, P=0.012) between BSA of at least
      1.9 m(2) and incidence of CAC. CONCLUSION: Elevated BSA is a predictor of CAC
      incidence, whereas elevated BMI is not. Moreover, elevated BSA is a predictor of
      CAC incidence particularly in men.

PMID- 22157359
TI  - What is the role of titin in active muscle?
AB  - Several properties of muscle defy explanation solely based on the sliding
      filament-swinging cross-bridge theory. Indeed, muscle behaves as though there is
      a dynamic "spring" within the sarcomeres. We propose a new "winding filament"
      mechanism for how titin acts, in conjunction with the cross-bridges, as a force
      dependent spring. The addition of titin into active sarcomeres resolves many
      puzzling muscle characteristics.

PMID- 22157360
TI  - Toddlers with anasarca and severe anemia:  a lesson in preventive medicine.
AB  - Two toddlers presented to their primary medical providers with anasarca and
      severe anemia. Laboratory evaluation revealed iron deficiency along with
      hypoproteinemia and hypoalbuminemia. Both children were diagnosed with iron
      deficiency anemia and were suspected to have an associated protein-losing
      enteropathy. A brief review of the literature is provided, and data supporting
      the notion of protein-losing enteropathy being a consequence of severe iron
      deficiency anemia are discussed. The American Academy of Pediatrics
      recommendations for prevention of iron deficiency anemia are reviewed. These
      cases illustrate the importance of the primary medical care provider's role in
      preventive medicine and provide an example of severe complications that may arise
      from iron deficiency anemia if it is not recognized and treated early.

PMID- 22157361
TI  - Cocooning:  a concept to protect young children from infectious diseases.
AB  - PURPOSE OF REVIEW: Despite focused efforts aimed at preventing infectious
      diseases among infants, recent years have seen a surge of infections among this
      population, particularly in pertussis, reminiscent of the 1940s prevaccine era.
      Given these trends, this review serves to discuss cocooning for infants against
      pertussis and its more recent application in influenza, and the barriers to and
      facilitators of this important strategy. RECENT FINDINGS: Infection with
      pertussis and influenza remains a significant cause of hospitalization among
      infants aged less than 1 year. Simultaneously, uptake of both tetanus,
      diphtheria, and acellular pertussis (Tdap) and influenza vaccines is very low
      among adults reporting close contact with an infant. To date, widespread
      implementation of cocooning has been thwarted by both individual-level and system
      level issues, although general acceptance of vaccination is high in settings in
      which cocooning is encouraged. SUMMARY: Better characterization and improvement
      of the cocooning strategy are necessary. Additionally, longitudinal research
      evaluating the effectiveness of cocooning against pertussis and influenza is
      essential. Ultimately, the effectiveness of cocooning to produce sustained
      control of infections will be dependent on healthcare provider advocacy, patient
      education, implementation and enforcement of policies, and the development of
      cost-effective programs.

PMID- 22157362
TI  - New advances in the diagnosis and treatment of autoimmune lymphoproliferative
      syndrome.
AB  - PURPOSE OF REVIEW: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder
      of disrupted lymphocyte homeostasis, resulting from mutations in the Fas
      apoptotic pathway. Clinical manifestations include lymphadenopathy, splenomegaly,
      and autoimmune cytopenias. A number of new insights have improved the
      understanding of the genetics and biology of ALPS. These will be discussed in
      this review. RECENT FINDINGS: A number of key observations have been made
      recently that better define the pathophysiology of ALPS, including the
      characterization of somatic FAS variant ALPS, the identification of
      haploinsufficiency as a mechanism of decreased Fas expression, and the
      description of multiple genetic hits in FAS in some families that may explain the
      variable penetrance of the disease. In addition, ALPS has been shown to be a more
      common condition, as patients diagnosed with other disorders, including Evans
      syndrome and common variable immune deficiency, have been found to have ALPS.
      Finally, the treatment of the disease has changed as splenectomy and rituximab
      have been shown to have unexpected ALPS-specific toxicities, and mycophenolate
      mofetil and sirolimus have been demonstrated to have marked activity against the
      disease. SUMMARY: On the basis of novel advances, the diagnostic algorithm and
      recommended treatment for ALPS have changed significantly, improving quality of
      life for many patients.

PMID- 22157363
TI  - An overview of cholera vaccines and their public health implications.
AB  - PURPOSE OF REVIEW: The current cholera pandemic now involves almost the entire
      developing world and represents an important global challenge. Though improved
      water and sanitation remain the mainstays of cholera prevention efforts, major
      improvements to infrastructure continue to be a goal far out of reach for many of
      those affected and near-term interventions, including vaccines, need
      consideration. RECENT FINDINGS: Prolonged and frequent epidemics, increased
      antimicrobial resistance, and heightening awareness of the role of climate change
      in disease burden have returned cholera to the forefront of the international
      public health forum. The availability of new oral cholera vaccines and supporting
      data have prompted the WHO to recommend vaccination be used with other prevention
      and control strategies where disease is endemic, and their use should be
      considered in outbreak situations. SUMMARY: Vibrio cholerae, a highly
      transmissible organism, is found in aquatic reservoirs and is not an eradicable
      disease. New variant strains appear to cause more severe clinical disease, and
      may be displacing earlier seventh pandemic organisms as the major cause of
      cholera. Licensed newer-generation oral vaccines have proven to be well
      tolerated, protective (including against new variant strains), and affordable and
      offer a new tool to control cholera.

PMID- 22157365
TI  - Long-term outcomes after posterior spine fusion for adolescent idiopathic
      scoliosis.
AB  - PURPOSE OF REVIEW: To summarize recent literature regarding long-term follow-up
      after spinal fusion for patients with adolescent idiopathic scoliosis. In
      particular, this review includes a review of research which provides insight into
      long-term results after fusion using pedicle screw stabilization, a relatively
      new technique for which long-term follow-up is only recently available. RECENT
      FINDINGS: The literature increasingly uses patient-derived questionnaires to
      report outcomes. Minor residual scoliosis after fusion does not adversely affect
      outcomes and is well tolerated by patients without causing functional
      limitations. In contrast, patients who are leaning forward after fusion
      ('positive sagittal balance') do worse as measured by validated outcomes
      instruments. Although patients who undergo long fusion have higher rates of disc
      degeneration on magnetic resonance imaging compared with the general population,
      this degeneration is most often clinically silent. SUMMARY: The best available
      evidence suggests that most patients do well after posterior fusion for
      adolescent idiopathic scoliosis, although outcomes are adversely affected if
      patients develop positive sagittal balance. Continued surveillance will determine
      whether accelerated degeneration at unfused levels becomes symptomatic at longer
      term follow-up or remains clinically silent.

PMID- 22157364
TI  - Management of chronic hepatitis C infection in children.
AB  - PURPOSE OF REVIEW: Chronic hepatitis C infection remains a global public health
      burden and has important clinical implications due to progressive liver fibrosis
      and development of cirrhosis and its complications. The role of antiviral therapy
      in infected children is an area of controversy due to an indolent clinical course
      in the majority of children, and a low likelihood of viral eradication in
      response to an intensive interferon-based treatment course that is associated
      with a wide spectrum of adverse effects. This review summarizes new concepts in
      the epidemiology, natural history, and management of chronic hepatitis C
      infection in children. RECENT FINDINGS: In the past 18 months, two large
      prospective studies demonstrated high rates of sustained virologic response in
      children with chronic hepatitis C infection, estimated at 53% in genotype 1 with
      peginterferon alpha-2b-ribavirin, and 47% in genotype 1 with peginterferon alpha
      2a-ribavirin. On this basis, both combination regimens have been recently
      approved by the Food and Drug Administration (FDA) for use in children. SUMMARY:
      Children with hepatitis C infection may benefit from early treatment, and the
      decision to pursue antiviral therapy should be based on individual assessment of
      host and viral characteristics, and stage of liver fibrosis.

PMID- 22157366
TI  - Progress in standard of care therapy and modest survival benefits in the
      treatment of non-small cell lung cancer patients in the Netherlands in the last
      20 years.
AB  - INTRODUCTION: Lung cancer is the leading cause of cancer mortality worldwide. We
      analyzed changes in treatment and their potential effect on survival of non-small
      cell lung cancer (NSCLC) patients in the Netherlands. METHODS: All NSCLC patients
      diagnosed during 1989-2009 (n=147,760) were selected from the population-based
      Netherlands Cancer Registry. Differences in treatment over time were tested by
      the Cochran-Armitage trend test. The effects of sex, age, histology, and
      treatment on relative survival were estimated in multivariable models. Follow-up
      was completed until January 1, 2010. RESULTS: Between 1989 and 2009, the
      proportion of younger patients (younger than 75 years) with stage I undergoing
      surgery increased from 84 to 89% and among elderly (75 years or elder) from 35 to
      49%; for stage II, this proportion decreased from 80 to 70% and remained about
      25% in respectively younger and older patients. Adjuvant chemotherapy for stage
      II increased to from 0 to 24% in younger patients but remained less than 5% among
      the elderly. Chemoradiation increased from 8 to 43% among younger patients with
      stage III and from 1 to 13% among elderly. In stage IV, chemotherapy in younger
      patients increased from 10 to 54% and in elderly from 5 to 21%. Five-year
      relative survival of the total group increased from 14.8 to 17% (especially among
      females, younger patients, and within each stage), which could be partly
      explained by changes in treatment and better staging. CONCLUSIONS: Over a 20-year
      period, application of therapy, which is currently considered as standard, has
      improved. This resulted in small improvements in survival within all stages.

PMID- 22157367
TI  - Phase II randomized trial of erlotinib or vinorelbine in chemonaive, advanced,
      non-small cell lung cancer patients aged 70 years or older.
AB  - INTRODUCTION: The primary objective of this study was to compare the response
      rates of elderly, chemonaive patients with advanced non-small cell lung cancer
      (NSCLC) treated with daily oral erlotinib versus oral vinorelbine. METHODS:
      Chemonaive Taiwanese patients aged 70 years or older who had advanced NSCLC were
      randomized to receive either oral erlotinib 150 mg (E) daily or oral vinorelbine
      60 mg/m (V) on days 1 and 8 every 3 weeks. RESULTS: From February 2007 to July
      2008, 116 patients were enrolled and 113 were included in the intent-to-treat
      population: 57 patients in the E group and 56 patients in the V group. Objective
      response rates were 22.8% (13 of 57) in E and 8.9% (5 of 56) in V (p = 0.0388).
      Median progression-free survival (PFS) was 4.57 months in E and 2.53 months in V
      (p = 0.0287), with an 80.6% increase in median PFS for E compared with V. Median
      survival time was 11.67 months in E and 9.3 months in V (p = 0.6975). Toxicities
      were generally mild in both groups. Median PFS was longest for epidermal growth
      factor receptor gene (EGFR)-mutated patients in the E group, followed by EGFR
      mutated patients in V, EGFR wild type in E, and EGFR wild type in V (p = 0.0034).
      Overall survival was longer for EGFR-mutated patients than for EGFR wild-type
      patients (p < 0.0001). CONCLUSIONS: Erlotinib is highly effective compared with
      oral vinorelbine in elderly, chemonaive, Taiwanese patients with NSCLC. EGFR
      mutated patients had better survival than those with EGFR wild-type disease,
      regardless of the treatment received.

PMID- 22157368
TI  - Results of proton beam therapy without concurrent chemotherapy for patients with
      unresectable stage III non-small cell lung cancer.
AB  - INTRODUCTION: This study was performed retrospectively to evaluate the outcome of
      patients with stage III non-small cell lung cancer (NSCLC) after proton beam
      therapy (PBT) alone. METHODS: The subjects were 57 patients with histologically
      confirmed NSCLC (stage IIIA/IIIB: 24/33) who received PBT without concurrent
      chemotherapy. The cohort included 32 cases of squamous cell carcinoma, 18
      adenocarcinoma, and 7 non-small cell carcinoma. Lymph node metastases were N0 7,
      N1 5, N2 30, and N3 15. Planned total doses ranged from 50 to 84.5 GyE (median,
      74 GyE). RESULTS: Planned treatment was completed in 51 patients (89%). At the
      time of analysis, 20 patients were alive, and the median follow-up periods were
      16.2 months for all patients and 22.2 months for survivors. The median overall
      survival period was 21.3 months (95% confidence interval: 14.2-28.4 months), and
      the 1- and 2-year overall survival rates were 65.5% (52.9-78.0%) and 39.4% (25.3
      53.5%), respectively. Disease progression occurred in 38 patients, and the 1- and
      2-year progression-free survival rates were 36.2% (23.1-49.4%) and 24.9% (12.7
      37.2%), respectively. Local recurrence was observed in 13 patients, and the 1-
      and 2-year local control rates were 79.1% (66.8-91.3%) and 64.1% (47.5-80.7%),
      respectively. Grade >= 3 lung toxicity was seen in six patients, esophageal
      toxicity occurred at grade <= 2, and there was no cardiac toxicity. CONCLUSION:
      The prognosis of patients with unresectable stage III NSCLC is poor without
      chemotherapy. Our data suggest that high-dose PBT is beneficial and tolerable for
      these patients.

PMID- 22157369
TI  - Detection of EGFR mutation status in lung adenocarcinoma specimens with different
      proportions of tumor cells using two methods of differential sensitivity.
AB  - INTRODUCTION: To evaluate epidermal growth factor receptor (EGFR) mutation status
      in lung adenocarcinoma specimens with different proportions of tumor cells using
      two methods with different sensitivities. METHODS: EGFR mutation status was
      determined by peptide nucleic acid (PNA) clamping and direct sequencing. The
      samples consisted of 41 cell blocks of malignant pleural effusions with various
      proportions of tumor cells, as well as 23 lung biopsy specimens containing more
      than 20% tumor cells and the corresponding surgically resected tumors. RESULTS:
      In the analysis of malignant pleural effusions, EGFR mutations were detected only
      by PNA clamping in four of nine patients who exhibited partial response to EGFR
      tyrosine kinase inhibitors; all the cell blocks of these four patients contained
      less than 20% tumor cells. Direct sequencing revealed wild-type EGFR, whereas PNA
      clamping revealed mutant EGFR, in one of five patients who exhibited progressive
      disease in response to EGFR tyrosine kinase inhibitor; the cell block of this
      patient contained a high proportion of tumor cells. A comparison of biopsy
      specimens containing sufficient tumor cells and the corresponding surgically
      resected tumors revealed discordance in the EGFR mutation status in four patients
      based on PNA clamping, whereas no discrepancies were observed by direct
      sequencing. CONCLUSIONS: Highly sensitive methods, such as PNA clamping, may be
      superior to direct sequencing for the detection of EGFR mutations in diagnostic
      specimens with a low proportion of tumor cells. Direct sequencing may be more
      representative when diagnostic specimens with a high proportion of tumor cells
      are available.

PMID- 22157370
TI  - Efficacy and safety of pemetrexed maintenance therapy versus best supportive care
      in patients from East Asia with advanced, nonsquamous non-small cell lung cancer:
      an exploratory subgroup analysis of a global, randomized, phase 3 clinical trial.
AB  - INTRODUCTION: In a recent global phase 3 trial, patients with advanced non-small
      cell lung cancer (NSCLC), who had not progressed after four cycles of platinum
      based induction chemotherapy, were randomized to maintenance therapy with
      pemetrexed or placebo. The objective of this retrospective, exploratory, post hoc
      subgroup analysis was to compare outcomes of East Asian patients with non-East
      Asian patients treated with pemetrexed or placebo. METHODS: Only patients with
      nonsquamous histology were analyzed. Patients were grouped by enrollment location
      (East Asian = China, Korea, or Taiwan; non-East Asian = all other countries). The
      Kaplan-Meier method was used to calculate median progression-free survival (PFS)
      and overall survival (OS) times. Hazard ratios (HRs) were calculated using
      unadjusted Cox proportional hazard models. RESULTS: Of the 663 patients enrolled
      in the study, 481 patients had nonsquamous NSCLC: East Asian = 27% and non-East
      Asian = 73%. In the East Asian subgroup, there were more women, never smokers,
      and patients with adenocarcinoma. PFS was similar between the subgroups and
      significantly prolonged in patients treated with pemetrexed than placebo (median
      PFS: East Asian, 4.4 versus 1.6 months, HR = 0.42, p < 0.001; non-East Asian, 4.5
      versus 2.8 months, HR = 0.45, p < 0.001). OS was numerically prolonged in East
      Asians (median OS: pemetrexed, 19.7 months; placebo, 16.4 months) compared with
      non-East Asians (pemetrexed, 13.2 months; placebo, 8.5 months). Pemetrexed was
      reasonably well tolerated with few severe adverse events reported. CONCLUSION:
      The results of this subgroup analysis support pemetrexed as maintenance therapy
      for East Asian patients with advanced, nonsquamous NSCLC.

PMID- 22157372
TI  - Collegiality, partnerships, bias, and editorial integrity.

PMID- 22157371
TI  - Objective review of mediastinal lymph node examination in a lung cancer resection
      cohort.
AB  - BACKGROUND: Accurate staging of resected lung cancer requires mediastinal lymph
      node (MLN) examination. MLN dissection (MLND) and systematic sampling (SS) are
      acceptable procedures; random sampling (RS) and no sampling (NS) are not. Forty
      percent of US lung cancer resections have NS. We closely examined the pattern of
      MLN examination in a lung resection cohort. METHODS: This is a retrospective
      review of all lung cancer resections in Memphis, TN, from 2004 to 2007. We
      compared operating surgeons' claims to the pathology report and an audit of the
      operation narrative by an independent surgeon. RESULTS: Forty-five percent of
      resections were reported by surgeons as MLND, 8% RS, and 48% NS. None met
      pathology criteria for MLND, 9% were SS, 50% were RS, and 42% were NS. The
      concordance rate between the operating surgeon and pathology report was 39%. The
      surgeon audit suggested 29% of resections had MLND, 26% RS, and 45% NS.
      Concordance between operating and auditing surgeons was 71%. Sublobar resection,
      T1 stage, and age were associated with NS. CONCLUSIONS: Most resections had
      suboptimal MLN examination. Concordance was poor between surgeon claims,
      objective review of pathology reports, and an independent surgeon audit. The
      higher concordance between operating and auditing surgeons may suggest incomplete
      pathology examination of MLN material. The terms used by operating surgeons to
      describe MLN retrieval were often inaccurate.

PMID- 22157373
TI  - An innovative environment where empowered nurses flourish.
AB  - This month, the director of the Magnet Recognition Program(r) takes an in-depth
      look at the Magnet(r) model component structural empowerment. He examines the
      characteristics associated with this component and identifies successes and
      challenges associated with addressing this component.

PMID- 22157374
TI  - Strategies for nurse leaders to address aggressive and violent events.
AB  - According to a 2010 report from the Bureau of Labor Statistics, 48% of all
      nonfatal injuries from occupational assaults and violent acts occur in healthcare
      and social service settings. A recent increase in workplace violence has been
      noted causing a heightened awareness among nurses. Information is scarce both in
      the literature and in healthcare settings regarding the proper steps to take in
      the event that violence occurs and de-escalation techniques for aggressive
      behavior do not work. Nurse leaders should prioritize time to become involved in
      developing and implementing workplace violence policies including offering
      education for nurses to deal with aggressive behaviors and violent acts and,
      learn de-escalation techniques.

PMID- 22157375
TI  - 200 years of nursing--a chief nurse's reflections on practice, theory, policy,
      education, and research.
AB  - This bimonthly department, sponsored by the AONE, presents information to assist
      nurse leaders in shaping the future of healthcare through creative and innovative
      leadership. The strategic priorities of AONE anchor the editorial content. They
      reflect contemporary healthcare and nursing practice issues that challenge nurse
      executives as they strive to meet the needs of patients.

PMID- 22157376
TI  - Exploring influential nurse executive leadership: an interview with Marla Weston.
AB  - This department highlights nursing leaders who have demonstrated the ability to
      inspire and lead change. This competency is seen in the ability to create,
      structure, and implement organizational, local, national, and international
      change through strategic visioning, risk taking, and effective communication.
      This, the fourth in a series of interviews, profiles the experiences of ANA Chief
      Executive Officer Marla Weston, PhD, RN.

PMID- 22157377
TI  - Improving patient safety and optimizing nursing teamwork using crew resource
      management techniques.
AB  - OBJECTIVE: This project describes the application of the "sterile cockpit rule,"
      a crew resource management (CRM) technique, targeted to improve efficacy and
      safety for nursing assistants in the performance of patient care duties.
      BACKGROUND: Crew resource management techniques have been successfully
      implemented in the aviation industry to improve flight safety. Application of
      these techniques can improve patient safety in medical settings. METHODS: The
      Veterans Affairs (VA) National Center for Patient Safety conducted a CRM training
      program in select VA nursing units. One unit developed a novel application of the
      sterile cockpit rule to create protected time for certified nursing assistants
      (CNAs) while they collected vital signs and blood glucose data at the beginning
      of each shift. RESULTS: The typical nursing authority structure was reversed,
      with senior nurses protecting CNAs from distractions. This process led to
      improvements in efficiency and communication among nurses, with the added benefit
      of increased staff morale. CONCLUSION: Crew resource management techniques can be
      used to improve efficiency, morale, and patient safety in the healthcare setting.

PMID- 22157378
TI  - The role of the nurse research facilitator in building research capacity in the
      clinical setting.
AB  - With little guidance in the literature regarding best practices, clinical
      institutions have used different organizational models to meet the challenges of
      building research capacity. This article provides recommendations regarding the
      most productive models based on review of historical clinical research
      facilitation models and the results of a survey regarding extant models conducted
      among research facilitators who were members of the Midwest Nursing Research
      Society.

PMID- 22157379
TI  - Evidence-based practice councils: potential path to staff nurse empowerment and
      leadership growth.
AB  - OBJECTIVE: This study aimed to examine the effects of participation in staff
      nurse-led practice councils on nurse job satisfaction and professional
      development. BACKGROUND: Although evidence-based practice (EBP) has become a key
      component of improving the quality of care, few studies have examined how
      implementation of staff nurse led councils model affect the involved nurses.
      METHODS: A 3-stage evaluation involving ethnography, semi-structured
      phenomenological private interviews and a 10-item survey were conducted with
      nurses, managers and executives participating in or involved with EBP councils
      tasked with improving patient outcomes at 6 community hospitals in a single non
      profit hospital system. RESULTS: Five themes were identified as outcomes:
      empowerment, meaningfulness, leadership growth, exposure to quality improvement,
      and vision. CONCLUSIONS: Staff-led councils have the potential to improve quality
      of care, job satisfaction, vision and leadership provided that managers and
      executives are sufficiently prepared to work with and support the councils.

PMID- 22157380
TI  - Caring behaviors and job satisfaction.
AB  - OBJECTIVE: This study examined the relationship between nurses' expression of
      caring and job satisfaction. BACKGROUND: Nurses have encountered barriers in
      their ability to express caring and find meaning and value in their work, which
      contributes to a decline in job satisfaction. METHODOLOGY: A descriptive
      correlational study randomly surveyed 5,000 (N = 1,091) medical-surgical staff
      nurses. RESULTS: Participants demonstrated confidence in their ability to express
      caring. The participants reported positive job satisfaction. A correlation was
      established between Caring Efficacy Scale, Index of Work Satisfaction (IWS), and
      the 6 components of the IWS. Spending time with patients was found to be a
      predictor of the nurses' ability to express caring behaviors. CONCLUSIONS: Caring
      and job satisfaction were correlated. Time was a predictor of their ability to
      express caring. Participants' age, years in nursing, and years in the same
      institution influenced both how nurses perceived their ability to express care
      and their level of job satisfaction.

PMID- 22157381
TI  - Lessons learned from implementation of postdischarge telephone calls at Baylor
      Health Care System.
AB  - Postdischarge telephone calls can enhance patient satisfaction, outcomes, and
      care continuity. The authors describe the Dallas-Fort Worth-based Baylor Health
      Care System standardized process for placing emergency department discharge
      telephone calls to patients. The metrics and guidelines related to the process as
      well as lessons learned, models of care, the future state of the postdischarge
      telephone calls, and findings are discussed.

PMID- 22157382
TI  - Using portfolios to introduce the clinical nurse leader to the job market.
AB  - Development of a portfolio is an effective strategy used by clinical nurse
      leaders (CNLs) to inform prospective employers of their specialized skills in
      quality improvement, patient safety, error prevention, and teamwork. The
      portfolio provides evidence of competence relative to the role of clinician,
      outcomes manager, client advocate, educator, information manager, systems
      analyst/risk anticipator, team manager, healthcare professional, and lifelong
      learner. This article describes the CNL portfolio developed by experts from the
      University of Tennessee Health Science Center and Methodist LeBonheur Healthcare.
      Examples of portfolio documents generated throughout the master's entry CNL
      curriculum are provided, along with student experiences using the portfolio in
      the employment interview process.

PMID- 22157383
TI  - Response from the southwest Florida nursing community supporting the future of
      nursing.
AB  - The aim of this study was to examine community hospital nurses' interest and
      potential barriers in pursuing advanced education. In October 2010, nursing
      leaders in Florida formed a task force to implement the Institute of Medicine
      Future of Nursing recommendations pertaining to the education of nurses. A survey
      based descriptive analysis of nurses employed at 3 community hospitals in Florida
      was performed. A total of 746 nurses answered open-ended questions related to
      current status in regard to advancing education. The greatest barriers were (1)
      time constraints, specifically family and work schedule conflicts, and (2)
      financial concerns. Eleven percent (n = 73) noted the lack of pay incentive and
      11% (n = 71) noted that they were nearing retirement. The findings bring an
      evidence-based approach to summarizing the trials, concerns, and barriers to
      nurses continuing their education. The Web-based survey proved to be a useful
      tool to quickly and inexpensively gather feedback from nurses concerning their
      plans and perceived barriers related to continuing their education.

PMID- 22157384
TI  - Differentiated essential competencies: a view from practice.
AB  - This article describes the results of strategies to elicit views of practicing
      nurses by the Texas Board of Nursing regarding competencies expected of new
      graduate licensed vocational nursing/LPN, associate degree/diploma, and
      baccalaureate nurses. The implications of these perceptions regarding the
      competencies expected of new graduates in Texas are considered, with questions
      posed for future exploration.

PMID- 22157385
TI  - Grape seed proanthocyanidin extract reduces renal ischemia/reperfusion injuries
      in rats.
AB  - Activation of reactive oxygen species and inflammation are implicated in renal
      ischemia/reperfusion (I/R) injuries. This study investigated whether grape seed
      proanthocyanidin extract (GSPE) protects against renal I/R injury by its effect
      on reactive oxygen species and the inflammation pathway. Wistar rats were
      administered GSPE before renal ischemia, followed by reperfusion for 24 hours.
      Plasma concentrations of urea, creatinine and cystatin C were measured for renal
      dysfunction. Serum and tissue superoxide dismutase activity and glutathione
      peroxidase and malondialdehyde levels were measured. Renal sections were analyzed
      for histological grading of renal injury, and nuclear factor-KB activity was
      determined. GSPE significantly reduced increases in urea, creatinine and cystatin
      C; increased kidney superoxide dismutase activity and glutathione peroxidase
      levels and reduced malondialdehyde levels. GSPE reduced histological renal damage
      and nuclear factor-KB activity. These results suggest that GSPE reduces renal
      dysfunction and injury caused by renal I/R.

PMID- 22157386
TI  - Multiple pulmonary metastases from giant cell tumor of a hand.
AB  - Giant cell tumor (GCT) of bone has been described as the most challenging benign
      bone tumors. The majority of these tumors, classically, are involved in the
      epiphysis of long bones; however, on rare occasions, the tumors occur in the
      small bones of hands and feet. Although this disorder is benign, GCTs show a
      tendency of significant bone destruction, local recurrence and, occasionally,
      pulmonary metastasis. Approximately 3% of GCTs is known to metastasize to the
      lung. Herein, the authors describe an extremely rare case of multiple pulmonary
      metastatic GCTs in a 54-year-old man who presented asymptomatic pulmonary nodular
      lesions detected incidentally on chest x-ray of routine health checkup. He
      underwent chemotherapy with adriamycin and cisplatin and achieved nearly complete
      remission.

PMID- 22157387
TI  - Chronic granulomatous disease in an adult recognized by an invasive
      aspergillosis.
AB  - A 20-year-old man without any history of a pulmonary disease presented initially
      with a 1-day history of fever and tachypnea and developed an acute respiratory
      failure within 24 hours. Microbiological and histological examinations raised an
      invasive pulmonary aspergillosis (IPA). A chronic granulomatous disease was
      identified as the predisposing factor leading to this severe fungal infection.
      Chronic granulomatous disease is caused by a reduced ability of phagocytes to
      mount an oxidative burst due to a defect in the nicotinamide adenine dinucleotide
      phosphate oxidase. Although IPA occurs usually in severely immunocompromised
      patients, it should be kept in mind that there are an increasing number of cases
      developing IPA in the setting of apparent health or to date undiagnosed
      immunodeficiency that requires further diagnostics.

PMID- 22157388
TI  - Cervicovaginal inflammatory cytokines and sphingomyelinase in women with and
      without bacterial vaginosis.
AB  - INTRODUCTION: The objective is to analyze proinflammatory cytokines [interleukin
      1beta (IL-1beta), interleukin-6 and tumor necrosis factor-alpha] and
      sphingomyelinase in women with bacterial vaginosis (BV), cervicitis and
      vaginitis. METHODS: From January 2009 to June 2010, human immunodeficiency virus
      (HIV)-negative, nonpregnant, married women, living with husband, aged 20 to 40
      years were recruited from a slum at Hyderabad, India, after taking written
      consent. One hundred forty-six women including 61 women with BV, 47 women with
      intermediate flora and 38 women with normal vaginal flora were evaluated for
      local proinflammatory cytokines and sphingomyelinase. Cervicitis and vaginitis
      were also analyzed by scoring white blood cells in the cervix and vaginal smears,
      respectively. RESULTS: Of the 146 women, 50.7% had cervicitis and 19.5% had
      vaginitis. IL-1beta, tumor necrosis factor-alpha and interleukin-6 levels were
      significantly high in women with cervicitis (P < 0.001) and vaginitis (P < 0.001)
      and IL-1beta in BV (P < 0.005), intermediate flora (P < 0.05) when compared with
      normal women. High vaginal pH was associated with IL-1beta. Neutral
      sphingomelinase showed an inverse association (P < 0.05) with cervicitis. Acid
      sphingomelinase directly correlated with IL-1beta although not significantly.
      CONCLUSIONS: This study shows proinflammatory response not only in BV but also in
      women with vaginitis and cervicitis. These conditions are likely to be important
      in promoting the transmission of HIV-1 and should be the focus of HIV prevention
      strategies.

PMID- 22157389
TI  - Comparison of self-perceived oral health, periodontal inflammatory conditions and
      socioeconomic status in individuals with and without prediabetes.
AB  - INTRODUCTION: The aim was to compare the self-perceived oral health, periodontal
      inflammatory conditions and socioeconomic status (SES) in patients with and
      without prediabetes. METHODS: Thirty-nine individuals [19 patients with
      prediabetes (test group) and 20 control individuals (control group)], at least 20
      years old were included. Plaque index, bleeding on probing, probing depth (4 to
      <6 mm and >=6 mm) and number of missing teeth were recorded. Fasting blood
      glucose levels were recorded, and marginal bone loss was measured on radiographs.
      SES, education status, self-perceived oral health, family history of diabetes and
      tobacco habits were also investigated. RESULTS: Mean ages of individuals in the
      test and control groups were 40.6 and 42.3 years, respectively. Plaque index,
      bleeding on probing, probing depth (4 to <6 mm and >=6 mm) and number of missing
      teeth were higher in the test group as compared with the control group (P <
      0.05). Premolar and molar marginal bone loss was higher in the test group as
      compared with the control group (P < 0.001). Self-perceived bleeding gums was
      more often reported by individuals in the test group as compared with the control
      group. A poor SES and education status was higher among individuals in the test
      group as compared with the control group (P < 0.001). CONCLUSIONS: Self-perceived
      gingival bleeding and clinical periodontal inflammation were severe in patients
      with prediabetes as compared with controls. An underprivileged SES aggravated
      periodontal conditions in patients with prediabetes.

PMID- 22157390
TI  - Double impairment: clinical identification of 33 cases of cerebellar ataxia with
      bilateral vestibulopathy.
AB  - OBJECTIVE: Following recently described small series of patients with the
      syndrome of cerebellar ataxia with bilateral vestibulopathy (CABV), the authors
      undertook a careful clinical and laboratory assessment of patients who presented
      to their unit with characteristics of this syndrome. STUDY DESIGN: Case note
      review. SETTING: Tertiary, university-based, multidisciplinary neurootology
      clinic. SUBJECTS: Thirty-three patients whose characteristics fit this syndrome.
      METHODS: Patients presenting to the Multidisciplinary Neurotology Clinic with
      characteristics of CABV were entered into a bespoke database. This was analyzed
      to identify the clinical findings and results of vestibular investigations for
      this group. RESULTS: Patients presented at a mean age of 54 years (SD, 17.6) with
      symptoms having been present for a median of 3 years (interquartile ratio, 2.0
      9.5). Caloric testing greatly underestimated the disorder, being subnormal in
      only 18% of patients; the head-thrust test was abnormal and dynamic visual acuity
      testing was abnormal 88% and 91% of the time, respectively. Of the patients, 76%
      demonstrated gaze-evoked nystagmus. Impaired smooth pursuit (97% of patients
      showed low gain with saccadic corrections) and impaired cancellation of the
      vestibulo-ocular reflex (in 97% of patients) were found. Impaired saccular
      otolithic function was abnormal in 33%, adding to patient imbalance. CONCLUSION:
      The unique double-pathway balance impairment in CABV patients causes a high
      prevalence of subnormal function of both central and peripheral vestibular
      function. This is an easily missed clinical entity that is often associated with
      normal caloric investigations. As many patients with this syndrome are poor
      candidates for vestibular rehabilitation therapy, resources are better devoted to
      the early implementation of assistance with their safe ambulation and activities
      of daily living.

PMID- 22157391
TI  - Association between otitis media and gastroesophageal reflux: a systematic
      review.
AB  - OBJECTIVE: To systematically review the association between otitis media and
      gastroesophageal/laryngopharyngeal reflux in children. DATA SOURCES: Cochrane
      library, MEDLINE (1966-September 2011), EMBASE (1974-September 2011), proceedings
      of International Symposia on Recent Advances in Otitis Media, and reference lists
      of relevant selected articles. REVIEW METHODS: Studies with planned data
      collection, in children with chronic otitis media with effusion/recurrent acute
      otitis media, assessing gastroesophageal/laryngopharyngeal reflux,
      pepsin/pepsinogen in middle ear, or antireflux therapy, were included. RESULTS:
      Of 242 initial studies, 15 met inclusion criteria. The authors found a mean
      prevalence of gastroesophageal reflux disease in children with chronic otitis
      media with effusion of 48.4% (range, 17.6%-64%) and in children with recurrent
      acute otitis media of 62.9% (range, 61.5%-64.3%). A mean prevalence of
      laryngopharyngeal reflux of 48.6% (range, 27.3%-70.6%) was found in children with
      otitis media. Mean pepsin/pepsinogen presence in otitis media was 85.3% (range,
      60%-100%) and of enzymatic activity was 34.2% (range, 14.5%-73%). Two randomized
      trials could not find benefit after antireflux treatment for 3 months, with an
      absolute rate difference (95% confidence interval) of 0.23 (0.023-0.42) and 0.13
      (-0.086 to 0.34), respectively. Reporting of adverse events was limited, or
      absent, in most studies. CONCLUSION: The prevalence of gastroesophageal reflux
      disease in children with chronic otitis media with effusion/recurrent acute
      otitis media may be higher than the overall prevalence for children. Presence of
      pepsin/pepsinogen in the middle ear could be related to physiologic reflux. A
      cause-effect relationship between pepsin/pepsinogen in the middle ear and otitis
      media is unclear. Antireflux therapy for otitis media cannot be endorsed based on
      existing research.

PMID- 22157392
TI  - Safety and efficacy of topical azithromycin ophthalmic solution 1.0% in the
      treatment of contact lens-related dry eye.
AB  - PURPOSE: The purpose of this pilot study was to evaluate the safety and efficacy
      of azithromycin ophthalmic solution 1% in patients with contact lens-related dry
      eye (CLDE). METHODS: This was a 4-week, single-center, open-label clinical trial
      in patients diagnosed with CLDE using the Contact Lens Dry Eye Questionnaire
      (CLDEQ). Fifty patients were enrolled in this study. The patients were randomized
      to 1 of 2 treatment groups: azithromycin ophthalmic solution administered bid on
      days 1 and 2 and on days 3 to 29+/-1 or Visine for Contacts rewetting drops
      administered qid on days 1 to 29+/-1. The patient diaries were used daily to
      collect data on comfortable and total contact lens wear time and ocular dryness
      throughout the treatment period. Tear osmolarity, fluorescein corneal staining,
      and visual acuity were also assessed during clinic visits. RESULTS: Fifty
      patients were enrolled, and 44 completed the study. One patient discontinued in
      the azithromycin group, and five patients discontinued in the rewetting drops
      group because of adverse events. A statistically significant increase in mean
      comfortable contact lens wear time from baseline was observed for the subjects
      treated with azithromycin ophthalmic solution as compared with the subjects
      treated with rewetting drops at week 4 (P=0.004; primary endpoint), in addition
      to weeks 2 and 3. The improvement in the mean comfortable wear time for the
      patients in the azithromycin treatment group exceeded 2 hrs throughout the
      treatment period (weeks 1-4). No significant differences were observed between
      the groups for total wear time, low contrast visual acuity, or tear osmolarity.
      Subject-rated ocular dryness (PM time assessments) was significantly improved
      from baseline in the subjects treated with azithromycin ophthalmic solution as
      compared with those treated with rewetting drops at weeks 2 and 3 endpoints
      (P=0.015 for each week). Additionally, a statistical difference was observed in
      favor of the azithromycin treatment group at week 2 for the subjects
      reclassifying as nondry eye as determined by the CLDEQ (P=0.05). CONCLUSIONS:
      Treatment with topical azithromycin ophthalmic solution was well tolerated and
      resulted in a significant improvement in comfortable contact lens wear time in
      the patients with CLDE.

PMID- 22157393
TI  - Dose-dependent and synergistic effects of proteoglycan 4 on boundary lubrication
      at a human cornea-polydimethylsiloxane biointerface.
AB  - OBJECTIVES: Proteoglycan 4 (PRG4), also known as lubricin, is a boundary
      lubricating mucin-like glycoprotein present on several tissue surfaces in the
      body. The objectives of this study were to (1) implement and characterize an in
      vitro boundary lubrication test at a human cornea-polydimethylsiloxane (PDMS)
      biointerface and (2) determine the dose-dependent and synergistic effects of
      PRG4, with hyaluronan (HA), on ocular surface boundary lubrication using this
      test. METHODS: Human corneas and model PDMS material were articulated against
      each other, at effective sliding velocities v(eff) between 0.3 and 30 mm/sec
      under physiologic loads of approximately 8 to 25 kPa. Samples were tested
      serially in (1) saline, PRG4 at 30, 100, 300 MUg/mL resuspended in saline, then
      saline again or (2) saline, AQuify Comfort Eye Drops (containing 0.1% HA), 300
      MUg/mL PRG4 in saline, 300 MUg/mL PRG4 in AQuify, then saline again. Both static
      and kinetic friction coefficients were calculated. RESULTS: PRG4 effectively
      lowered friction at the cornea-PDMS biointerface, both alone in a dose-dependent
      manner and in combination with HA. PRG4 reduced kinetic friction coefficients,
      <MU(kinetic, Neq)>, from approximately 0.30 in saline, to approximately 0.30,
      0.24, and 0.17 in 30, 100, and 300 MUg/mL PRG4, respectively. Values of
      <MU(kinetic, Neq)> in AQuify, approximately 0.32, were similar to those in
      saline; however, when combined with 300 MUg/mL PRG4, values of <MU(kinetic, Neq)>
      were reduced to approximately 0.15. CONCLUSIONS: PRG4 functions as an effective
      ocular surface boundary lubricant, both alone in a dose-dependent manner and in
      combination with HA.

PMID- 22157394
TI  - Effects of contact lenses on the ocular surface in patients with keratoconus:
      piggyback versus ClearKone hybrid lenses.
AB  - OBJECTIVE: Because patients with keratoconus tend to wear contact lens for a long
      period of time, they are more prone to ocular surface changes induced by the
      lenses. This study aimed to compare immunohistochemical changes induced by two
      different types of contact lenses in patients with keratoconus. METHODS: Twenty
      four contact lens-naive keratoconus patients (30 eyes) were included in this
      prospective study. Group 1 comprised 14 eyes (12 patients) wearing piggyback
      lenses, and group 2 comprised 16 eyes (12 patients) wearing ClearKone hybrid
      lenses. The patients were analyzed for bulbar conjunctival impression cytology,
      tear interleukin-6 (IL-6) and IL-8 levels, and confocal microscopic changes of
      the cornea before and 6 months after wearing contact lenses. RESULTS: Six months
      after wearing contact lenses, the groups demonstrated similar epithelial
      metaplasia rates, tear IL-6 and IL-8 levels, and similar confocal microscopy
      findings (P>0.05 for all intergroup comparisons). Among the parameters tested in
      this study, only IL-6 and IL-8 levels and posterior keratocyte density on
      confocal microscopy showed an increase after 6 months when compared with baseline
      values but at a similar degree in the two groups. CONCLUSIONS: This small sample
      was not able to demonstrate a difference between the two types of lenses with
      regard to the variables examined, and further larger trials would be required to
      determine if differences truly exist or not. However, clinicians may still
      consider patient comfort and vision in selecting the lens type in patients with
      keratoconus.

PMID- 22157395
TI  - Contact lens complications in an urgent-care population: the University of
      California, Los Angeles, contact lens study.
AB  - OBJECTIVES: This is a prospective study in an urgent-care ophthalmic setting to
      investigate contact lens (CL) complications and their association with extended
      wear (EW). METHODS: Data on CL designs, care system(s), and ocular complications
      were collected over a 6-month period. RESULTS: One thousand three hundred and
      sixty-nine patients presented to the Jules Stein Eye Institute urgent care with
      symptoms of eye problems. Of these, 56 were identified with diagnoses
      etiologically associated with CL wear, and 49 were studied. The five most common
      ocular diagnoses found in our study were in the following order: epithelial
      staining or abrasion/epithelial defect, conjunctival injection, papillae, corneal
      neovascularization, and presumed microbial keratitis (PMK). Fifteen of 49
      patients were diagnosed with PMK. The mean number of complications was 3.43 per
      eye. Most of the patients (65%) reported some form of EW. Analysis of the
      patients with PMK showed an association with EW. There seemed to be no
      statistical difference in the number of complications per symptomatic eye with
      hydrogel and silicone hydrogel lenses although 13 of the 15 patients with PMK
      were silicone hydrogel wearers. CONCLUSIONS: We studied various aspects of care
      and compliance in an urgent-care population and found that most of our urgent
      care patients slept with CLs on their eyes. Symptomatic CL wear-related
      complications, and specifically MK, strongly correlate with EW with less relation
      to lens design, material, and wear modality. We therefore conclude that CL EW is
      a risk factor leading to urgent-care visits.

PMID- 22157396
TI  - Gastrointestinal regulatory peptides and central nervous system mechanisms of
      weight control.
AB  - PURPOSE OF REVIEW: This review focuses on recent advances in understanding the
      multiple roles of gastrointestinal peptides in the control of food intake and
      body weight with specific emphasis on ghrelin, amylin and glucagon-like peptide
      1. RECENT FINDINGS: Recent studies support a role for ghrelin, amylin and
      glucagon-like peptide 1 in short-term and long-term effects on food intake and
      body weight. Apart from contributing to energy homeostasis, ghrelin's
      participation in reward and sensory processing has been the focus of much recent
      work. New findings on amylin's effects on food intake and energy balance provide
      further support for its role in meal-related food intake and suggest that it may
      also function as an adiposity signal. New investigations on the role of central
      and peripheral glucagon-like peptide 1 receptors in mediating the anorexic
      effects of glucagon-like peptide 1 have suggested that they differentially
      contribute to short-term and long term effects on food intake. SUMMARY:
      Gastrointestinal peptides can influence food intake through mechanisms that
      involve short-term meal-related effects or through activation of central pathways
      involved in energy balance. An appreciation of the multiple actions of
      gastrointestinal peptides on food intake will aid in developing new strategies
      for weight management.

PMID- 22157397
TI  - Cholecystokinin.
AB  - PURPOSE OF REVIEW: Cholecystokinin (CCK) controls nutrient delivery to the small
      intestine by inhibiting food intake and gastric emptying. This review deals with
      recent work shedding new light on how and when. RECENT FINDINGS: Intestinal I
      cells release CCK in response to dietary lipid and protein through mechanisms
      involving the G-protein-coupled receptors GPR40 and calcium-sensing receptor.
      Vagal afferent neurons are a primary target of CCK and are now recognized as an
      important site of integration of peripheral signals regulating ingestion. In
      addition to regulating vagal afferent nerve discharge, CCK also controls the
      expression of receptors and peptide neurotransmitters by these neurons; these
      actions are potentiated by leptin and inhibited by ghrelin. The responses of
      vagal afferent neurons to CCK are attenuated in obesity. Studies of human central
      nervous system responses using functional magnetic resonance imaging indicate
      activation of brainstem, hypothalamus and motor cortex by ingested fatty acid
      that is inhibited by a CCK-1 receptor antagonist. CCK may also play a role in
      adaptive responses in pancreatic islets by maintaining beta-cell mass and acting
      as an incretin in certain circumstances. SUMMARY: CCK mediates inhibition of food
      intake in response to ingested lipid and protein; resistance to CCK occurs in
      obesity and may contribute to altered mechanisms regulating food intake.

PMID- 22157398
TI  - Biology and pharmacology of bombesin receptor subtype-3.
AB  - PURPOSE OF REVIEW: This review summarizes the results of recent studies regarding
      the biology and pharmacology of novel synthetic agonists and antagonists of the
      bombesin receptor subtype-3 (BRS-3). RECENT FINDINGS: All three mammalian
      bombesin receptors including gastrin-releasing peptide receptor, the neuromedin B
      receptor, and the BRS-3 have been shown to regulate energy balance and appetite
      and satiety. Studies indicate that the orphan BRS-3 is an important regulator of
      body weight, energy expenditure, and glucose homeostasis. Endogenous bombesin
      like peptides bombesin, gastrin-releasing peptide, and neuromedin B receptor do
      not bind to BRS-3 and the endogenous BRS-3 ligand remains unknown. The novel
      synthesis of selective, high-affinity BRS-3 agonists and antagonists has recently
      been accomplished and showed that BRS-3 regulates energy balance independent of
      other established pathways and glucose-stimulated insulin secretion in the
      pancreatic islet cells. The availability of new BRS-3 selective agonists and
      antagonists will facilitate further elucidation of its role in energy
      homeostasis, and provides a potential approach for the pharmacological treatment
      of obesity and type 2 diabetes. SUMMARY: The native ligand of the G protein
      coupled BRS-3 has not been identified as of now. However, novel synthesis of
      small-molecule, high-affinity agonists and antagonists on the BRS-3 was used in
      the recent studies and demonstrated an important role of BRS-3 in the regulation
      of energy homeostasis and glucose metabolism.

PMID- 22157399
TI  - Peripheral chemosensing system for tastants and nutrients.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss the presence and
      possible roles of peripheral taste/nutrient sensors, particularly taste
      receptors. RECENT FINDINGS: Recent studies have demonstrated that taste signaling
      molecules are distributed not only in the gustatory epithelium, but also in other
      tissues, including the gastrointestinal tract, airways, testes and brain. Taste
      signaling mechanisms in the gastrointestinal tract were reported to participate
      in detecting sweet, umami and bitter compounds. Several research groups have
      suggested that tastant/nutrient detection by other systems contributes to the
      behavioral responses to food intake. SUMMARY: Taste-like cells expressing taste
      signaling components are distributed in multiple tissues. Investigation of their
      potential roles in chemosensing has just begun. Researchers have identified at
      least two chemosensory pathways in the gastrointestinal tract for detecting
      tastants/nutrients. One is the taste receptor signaling pathway and the other is
      the currently unknown nutrient-sensing pathway that elicits postingestive
      effects. The former system utilizes a mechanism similar to taste sensing in the
      oral cavity. By understanding how tastants/nutrients are sensed and regulated
      through both systems, we may be able to more effectively control food intake in
      the future.

PMID- 22157401
TI  - Inflammatory cytokines and growth in childhood.
AB  - PURPOSE OF REVIEW: In this review we report an update on the current knowledge on
      growth disorders in children with chronic inflammatory diseases, mainly
      inflammatory bowel disease and juvenile idiopathic arthritis, with a particular
      focus on the role of inflammatory cytokines as mediators of growth impairment.
      RECENT FINDINGS: Growth disorders are common among patients with inflammatory
      diseases. Several factors can contribute to growth failure: poor nutrition,
      immobilization, drugs, disease activity, duration and severity. There is
      extensive evidence suggesting that inflammatory cytokines are key players in
      mediating growth failure. Recent studies have confirmed a direct association
      between levels of inflammatory cytokines, such as tumour necrosis factor-alpha
      and interleukin-6, and reduced growth velocity, as well as impaired body
      composition. Recent studies have also highlighted the beneficial effect of new
      drugs, such biologics, not only in controlling disease activity, but also in
      improving growth. SUMMARY: Growth retardation remains a major problem in patients
      with chronic inflammatory diseases, and proinflammatory cytokines are key players
      in this context. New drugs, specifically targeting inflammatory cytokines appear
      to be promising for their effect on growth. Further studies are required to
      better characterize the cytokine profile in children with inflammatory disease
      and help in developing effective treatment strategies.

PMID- 22157400
TI  - Diagnosis of growth hormone deficiency in childhood.
AB  - PURPOSE OF REVIEW: The diagnosis of growth hormone deficiency (GHD) in childhood
      is challenging, in large part because of the lack of a true gold standard and the
      relatively poor performance of available diagnostic testing. This review
      discusses the recent literature on this topic. RECENT FINDINGS: Auxology and
      clinical judgment remain the foundation for the diagnosis of GHD. Provocative
      growth hormone testing is poorly reproducible, dependent on factors such as body
      composition and pubertal status, and further limited by significant variability
      among commercially available growth hormone assays. Measurement of insulin-like
      growth factor I and insulin-like growth factor-binding protein 3 is not
      diagnostically useful in isolation but is helpful in combination with other
      diagnostic measures. Neuroimaging is also useful to inform diagnosis, as
      pituitary abnormalities suggest a higher likelihood of GHD persisting into
      adulthood. Although genetic testing is not routinely performed in the diagnosis
      of GHD at the present time, multiple recent reports raise the possibility that it
      may play a more important role in diagnosing GHD in the future. SUMMARY: Beyond
      physicians' integrated assessment of auxology, clinical presentation, and bone
      age, current tools to diagnose GHD are suboptimal. Recent literature emphasizes
      the need to reappraise our current practice and to consider new tools for
      diagnosis.

PMID- 22157402
TI  - Genetic disorders of the pituitary.
AB  - PURPOSE OF REVIEW: To discuss pituitary development and function related to those
      factors in which molecular defects resulting in combined pituitary hormone
      deficiency have been described in humans, and to describe recently reported novel
      mutations in these factors (January 2010 to September 2011). RECENT FINDINGS:
      Novel mutations have been found in transcription factors involved in pituitary
      development, HESX1; LHX3; LHX4; SOX3; Prophet of Pit-1; and POU1FI, and in some
      of the signaling molecules expressed in the ventral diencephalon (fibroblast
      growth factor 8 and GLI2). There is phenotypic variability for the same mutation
      suggesting variable penetrance due to other genetic, epigenetic, or environmental
      factors. The incidence of mutations in these factors is low suggesting that other
      genes or environmental factors are responsible for the majority of cases of
      combined pituitary hormone deficiency. SUMMARY: Development of the pituitary
      gland and pituitary cell determination and specification depend on the expression
      and interaction of signaling molecules and transcription factors in overlapping,
      but distinct, spatial and temporal patterns. Studying genotype-phenotype
      correlations in patients with mutations in these factors give insight into the
      mechanisms involved in normal pituitary development and function.

PMID- 22157403
TI  - Short stature and its treatment in Turner and Noonan syndromes.
AB  - PURPOSE OF REVIEW: We review recent developments in the approach to the treatment
      of short stature in patients with Turner and Noonan syndromes. RECENT FINDINGS:
      Turner syndrome and Noonan syndrome are clinically defined conditions associated
      with short stature. The Food and Drug Administration (FDA) approved treatment
      with recombinant human growth hormone (hGH) for patients with Turner syndrome in
      1996 and for those with Noonan syndrome in 2007. Studies have shown that early
      appropriate use of hGH increases adult height in individuals with Turner
      syndrome. The combination of hGH and low-dose estrogen may also improve growth
      and adult height as well as possibly provide neurocognitive and behavioral
      benefits. Noonan syndrome is a genetically heterogeneous condition. In patients
      with Noonan syndrome phenotype, investigators have identified disease-associated
      genes (PTPN11, SOS1, RAF1, KRAS, and others). Treatment with hGH has been
      documented to result in short-term increases in growth velocity as well as modest
      gains in adult height. SUMMARY: Our understanding and management of short stature
      in children with Turner syndrome and Noonan syndrome has greatly advanced over
      the years. Recent developments with focus on these two common syndromes will be
      reviewed.

PMID- 22157404
TI  - Pituitary tumors in childhood.
AB  - PURPOSE OF REVIEW: This review focuses on recently published literature on
      pituitary tumors in children with special focus on craniopharyngioma and
      prolactinoma. Although most pituitary masses are benign neoplasms, they are
      associated with high morbidity and mortality related to their proximity to vital
      neurologic structures including the optic chiasm, hypophysis and hypothalamus,
      resulting in disruption of pituitary hormone secretion. RECENT FINDINGS: The role
      of Wingless/beta-beta catenin signaling and aryl hydrocarbon receptor-interacting
      protein mutations in pituitary tumor formation has been recognized. There is
      general agreement on optimal treatment of prolactinomas, although duration of
      medical therapy in children deserves more specific attention. Advances in
      imaging, medical, surgical and radiotherapy techniques have greatly increased
      survival rates for all pituitary tumors, but high recurrence rates after
      attempted complete resection and high progression rates after incomplete
      resection of craniopharyngioma remain troublesome. Long-term morbidity and late
      mortality of all pituitary tumors have become better appreciated with recent
      focus placed on severe obesity. A trend toward a more multidisciplinary approach
      for craniopharyngioma, including radiotherapy and chemotherapy, particularly when
      tumor burden involves the hypothalamus, continues. SUMMARY: A vast amount of
      literature has been recently published, focusing on the management and long-term
      sequelae of all pituitary tumors in children. Craniopharyngioma remains the most
      challenging mass arising within sellar and parasellar areas, and optimal
      treatment continues to be hotly debated. Recognizing the rarity of pediatric
      pituitary tumors, the field would greatly benefit from more prospective
      multicenter trials, as well as from standardization of the assessment of
      preoperative function and post-treatment outcomes.

PMID- 22157405
TI  - Recent research on inhaled corticosteroids and growth.
AB  - PURPOSE OF REVIEW: Description of recent studies evaluating growth and inhaled
      corticosteroids. RECENT FINDINGS: Corticosteroids are the gold standard of asthma
      maintenance treatment, but effects on growth remain controversial. This is a
      review of recent research in this area, which has focused on medications causing
      less adrenal suppression as well as alternative regimens for chronic illness such
      as asthma. SUMMARY: The use of newer corticosteroids and regimens shows short
      term evidence of minimal growth effects without worsening of asthma control.

PMID- 22157406
TI  - Update on disorders of sex development.
AB  - PURPOSE OF REVIEW: To review the recent information regarding disorders of sex
      development (DSD) which contribute to, as well as highlight, the need for greater
      understanding of genetic mutations and the dire need for specific outcome
      information. RECENT FINDINGS: New information is primarily related to the
      identification of genetic mutations and other gene variations that impact
      reproductive system development. These new data add to the increasingly complex
      list of genes and the multigenetic effects involved in DSD. Several reviews
      outline the approach to diagnosis and management of the patient with DSD and the
      importance of a multidisciplinary team. These reviews continue to demonstrate the
      lack of specific guidelines for complex DSD patients for whom sex assignment is
      problematic. SUMMARY: Although genetic research continues to define new and
      multigenetic factors involved in the development of DSD, this review of the
      medical literature also underscores the fact that scientific understanding
      remains inadequate in many areas of DSD to provide solid guidelines for
      approaching the more controversial questions in the DSD patient. Accordingly, the
      need for larger, outcome studies using subjects with verified diagnoses are
      needed. Optimally, these studies would account for potentially confounding
      differences in genetic, social, and psychological factors to help answer the
      pressing question facing every clinician dealing with DSD patients - what is the
      relationship between medical decision-making (such as sex assignment and genital
      surgery) and future quality of life and adaptation.

PMID- 22157407
TI  - Growth and development potpourri.

PMID- 22157408
TI  - Gastrointestinal regulatory peptides.

PMID- 22157409
TI  - Autism spectrum disorders and health care expenditures:  the effects of co
      occurring conditions.
AB  - OBJECTIVE: Children with autism spectrum disorders (ASDs) often have co-occurring
      conditions, but little is known on the effect of those conditions on their
      medical care cost. Medical expenditures attributable to ASDs among Medicaid
      enrolled children were calculated, and the effects of 3 commonly co-occurring
      conditions--intellectual disability (ID), attention deficit/hyperactivity
      disorder (ADHD), and epilepsy-on those expenditures were analyzed. METHODS: Using
      MarketScan Medicaid Multi-State Databases (2003-2005) and the International
      Classification of Disease, Ninth Revision, children with ASD were identified.
      Children without ASD formed the comparison group. The 3 co-occurring conditions
      were identified among both the ASD and the comparison groups. Annual mean,
      median, and 95th percentile of total expenditures were calculated for children
      with ASD and the co-occurring conditions and compared with those of children
      without ASD. Multivariate analyses established the influence of each of those co
      occurring conditions on the average expenditures for children with and without
      ASD. RESULTS: In 2005, 47% of children with ASD had at least 1 selected co
      occurring condition; attention deficit/hyperactivity disorder was the most
      common, at 30%. The mean medical expenditures for children with ASD were 6 times
      higher than those of the comparison group. Children with ASD and ID incurred
      expenditures 2.7 times higher than did children with ASD and no co-occurring
      condition. CONCLUSION: Medicaid-enrolled children with ASD incurred higher
      medical costs than did Medicaid-enrolled children without ASD. Among Medicaid
      enrolled children with ASD, cost varied substantially based on the presence of
      another neurodevelopmental disorder. In particular, children with ID had much
      higher costs than did other children with ASD.

PMID- 22157410
TI  - Cancer-related deaths among different treatment options in chronic coronary
      artery disease:  results of a 6-year follow-up of the MASS II study.
AB  - INTRODUCTION: The primary end points of randomized clinical trials evaluating the
      outcome of therapeutic strategies for coronary artery disease (CAD) have included
      nonfatal acute myocardial infarction, the need for further revascularization, and
      overall mortality. Noncardiac causes of death may distort the interpretation of
      the long-term effects of coronary revascularization. MATERIALS AND METHODS: This
      post-hoc analysis of the second Medicine, Angioplasty, or Surgery Study evaluates
      the cause of mortality of patients with multivessel CAD undergoing medical
      treatment, percutaneous coronary intervention, or surgical myocardial
      revascularization [coronary artery bypass graft surgery (CABG)] after a 6-year
      follow-up. Mortality was classified as cardiac and noncardiac death, and the
      causes of noncardiac death were reported. RESULTS: Patients were randomized into
      CABG and non-CABG groups (percutaneous coronary intervention plus medical
      treatment). No statistical differences were observed in overall mortality
      (P=0.824). A significant difference in the distribution of causes of mortality
      was observed among the CABG and non-CABG groups (P=0.003). In the CABG group, of
      the 203 randomized patients, the overall number of deaths was 34. Sixteen
      patients (47.1%) died of cardiac causes and 18 patients (52.9%) died of
      noncardiac causes. Of these, seven deaths (20.6%) were due to neoplasia. In the
      non-CABG group, comprising 408 patients, the overall number of deaths was 69.
      Fifty-three patients (77%) died of cardiac causes and 16 patients (23%) died of
      noncardiac causes. Only five deaths (7.2%) were due to neoplasia. CONCLUSION:
      Different treatment options for multivessel coronary artery disease have similar
      overall mortality: CABG patients had the lowest incidence of cardiac death, but
      the highest incidence of noncardiac causes of death, and specifically a higher
      tendency toward cancer-related deaths.

PMID- 22157411
TI  - Completely percutaneous transcatheter aortic valve implantation through
      transaxillary route: an evolving concept.

PMID- 22157412
TI  - Adult primary central nervous system vasculitis:  an update.
AB  - PURPOSE OF REVIEW: The aim of this review was to cover the recent major advances
      made in the fields of clinical assessment, diagnosis and treatment of adult
      primary central nervous system vasculitis (PCNSV). RECENT FINDINGS: To prevent
      misdiagnosis, particularly with the reversible cerebral vasoconstriction
      syndromes, new criteria on the basis of the levels of certainty of the diagnosis
      of PCNSV have been proposed. Advances in the neuroimaging techniques visualizing
      the wall of intracranial blood vessels have improved the capacity to distinguish
      inflammatory from noninflammatory vascular lesions. These techniques could play
      in the future an important role in the diagnosis of PCNSV. Studies of larger
      numbers of cases have revealed a more varied histopathological inflammatory
      picture and disclosed an association with amyloid angiopathy. It has also been
      recognized that PCNSV is a heterogeneous disorder encompassing clinical subsets
      that differ in terms of prognosis and therapy. Finally, differently from earliest
      reports that suggested a poor prognosis with a fatal outcome in the majority of
      the cases, a large recent study from Mayo Clinic has described a more favorable
      course with good response to therapy and a favorable outcome in 81% of cases.
      SUMMARY: Our better understanding of the PCNSV spectrum and its subsets will
      facilitate early recognition. This may facilitate earlier treatment and may
      prevent irreversible or even lethal outcomes.

PMID- 22157413
TI  - The latest on IgG4-RD:  a rapidly emerging disease.
AB  - PURPOSE OF REVIEW: Provide an update of the developments in IgG4 related disease
      within the last year in terms of nomenclature, diagnostic criteria and clinical
      features. RECENT FINDINGS: The number of diseases associated with IgG4 related
      disease continues to grow. The entities of idiopathic orbital inflammation,
      idiopathic cervical fibrosis, eosinophilic angiocentric fibrosis, reactive
      nodular fibrous pseudotumor, sclerosing mesenteritis, and membranous
      glomerulonephritis should all be added to the list of diseases associated with
      the IgG4 related disease spectrum. The issues of nomenclature and diagnostic
      criteria for IgG4 related disease have important recent developments as well.
      SUMMARY: The diagnosis of IgG4 related disease continues to be challenging.
      Increasing recognition of IgG4 related disease has led to a large body of
      literature on organ sites of involvement. Understanding how the disease manifests
      itself is critical to diagnosis and ultimately treatment.

PMID- 22157414
TI  - Autoimmune thyroid disease.
AB  - PURPOSE OF REVIEW: Autoimmune thyroid disorders (AITDs) are the most common organ
      specific autoimmune disorders. The genetics as well as clinical and laboratory
      manifestations of AITDs are reviewed. RECENT FINDINGS: We discuss the association
      between specific rheumatologic disorders and AITDs and manifestations of AITDs
      that mimic rheumatologic disorders. The recently discovered common molecular
      pathways involved in these processes are discussed. SUMMARY: AITDs and
      rheumatologic disorders have significant commonalities both clinically and
      etiologically. This information is important for rheumatologists and primary care
      physicians who care for patients with these disorders.

PMID- 22157415
TI  - Castleman disease and associated autoimmune disease.
AB  - PURPOSE OF REVIEW: Castleman disease can occur in association with autoimmune
      connective tissue disease and confound the clinical picture, resulting in delayed
      diagnosis and suboptimal treatment. This review focuses on the intersection of
      Castleman disease and autoimmunity with an emphasis on shared pathology and
      mutually beneficial treatments. RECENT FINDINGS: Targeting CD-20, interleukin-6,
      and the nuclear factor-kappaB pathway has shown promise in achieving long-term
      remission in patients with Castleman disease and associated autoimmune features.
      SUMMARY: Advances in understanding of pathogenic cell types and cytokines in
      Castleman disease have allowed the development of targeted therapies successful
      in the treatment of both Castleman disease and associated autoimmune disease.

PMID- 22157416
TI  - Langerhans cell histiocytosis and Erdheim-Chester disease.
AB  - PURPOSE OF REVIEW: To provide an updated overview of the pathogenesis and
      treatment of Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease
      (ECD). RECENT FINDINGS: There is ongoing debate as to the exact pathogenesis of
      these disorders and their classification as reactive versus neoplastic.
      Proinflammatory cytokines are known to play a role in both LCH and ECD and
      strengthen the hypothesis that, at least in part, they are disorders of immune
      dysregulation. The recent discovery of activating mutations in the proto-oncogene
      BRAF in a subset of LCH patients suggests that LCH is in fact a neoplastic
      disorder. Understanding of the mechanisms that promote proliferation and
      migration of histiocytes has led researchers to explore targeted immune
      modulatory therapies for ECD. Similarly for LCH, alternative chemotherapeutic
      agents and reduced-intensity hematopoietic stem cell transplant are being
      evaluated for refractory disease. SUMMARY: More research is needed to better
      understand the cause of these disorders and may help in identifying new targeted
      therapies, particularly for patients with refractory or relapsed disease.
      Multinational trials are ongoing for LCH and are urgently needed for ECD.

PMID- 22157417
TI  - Myelodysplasia and autoimmunity.
AB  - PURPOSE OF REVIEW: Primary myelodysplastic syndromes (MDS) are heterogeneous
      clonal haemopoietic stem-cell disorders clinically presented with a varying
      degree of peripheral cytopenias and an increased probability of leukemic
      evolution. The natural history of MDS ranges from more indolent forms of disease
      spanning years to those rapidly progressing to overt leukemia. A distinct subset
      of MDS patients manifest overt autoimmune manifestations (AIMs), the pathogenesis
      and prognostic significance of which remain controversial. This review will
      briefly highlight aspects of immune-mediated myelosuppression and cytokine
      induced cytopenias in MDS and further analyze MDS-associated AIMs clinically and
      pathogenetically. RECENT FINDINGS: Facts provided by advanced studies suggest
      that an immune reaction against the evolving clone, operated by macrophages, T,
      natural killer and other effectors contribute to ineffective and dysplastic MDS
      hemopoiesis. Despite the fact that several immunologic abnormalities have been
      described in MDS, the precise pathophysiologic mechanism underlying AIMs remains
      unclear. SUMMARY: The encouraging biological insights into the autoimmune
      component of MDS pathophysiology can lead to the development of novel forms of
      treatment for controlling MDS process. MDS with AIMs constitute an ideal model in
      the investigation of disordered immune function in preleukemic states.

PMID- 22157418
TI  - Spatiotemporal variation of crown-scale stomatal conductance in an arid Vitis
      vinifera L. cv. Merlot vineyard: direct effects of hydraulic properties and
      indirect effects of canopy leaf area.
AB  - Vineyards were planted in the arid region of northwest China to meet the local
      economic strategy while reducing agricultural water use. Sap flow, environmental
      variables, a plant characteristic (sapwood-to-leaf area ratio, A(s)/A(l)) and a
      canopy characteristic (leaf area index, L) were measured in a vineyard in the
      region during the growing season of 2009, and hourly canopy stomatal conductance
      (G(si)) was estimated for individual vines to quantify the relationships between
      G(si) and these variables. After accounting for the effects of vapor pressure
      deficit (D) and solar radiation (R(s)) on G(si), much of the remaining variation
      of reference G(si) (G(siR)) was driven by that of leaf-specific hydraulic
      conductivity, which in turn was driven by that of A(s)/A(l). After accounting for
      that effect on G(siR), appreciable temporal variation remained in the decline
      rate of G(siR) with decreasing vineyard-averaged relative extractable soil water
      (theta(E)). This variation was related to the differential decline oftheta(E)
      near each monitored vine, decreasing faster between irrigation events near vines
      where L was greater, thus adding to the spatiotemporal variation of G(siR)
      observed in the vineyard. We also found that the vines showed isohydric-like
      behavior whentheta(E) was low, but switched to anisohydric-like behavior with
      increasingtheta(E). Modeledtheta(E) and associated G(s) of a canopy with even L
      (1.9 m(2) m(-2)) were greater than that of the same average L but split between
      the lowest and highest L observed along sections of rows in the vineyard (1.2 and
      2.6 m(2) m(-2)) by 6 and 12%, respectively. Our results suggest that managing
      sectional L near the average, rather than allowing a wide variation, can reduce
      soil water depletion, maintaining G(s) higher, thus potentially enhancing yield.

PMID- 22157419
TI  - Quality improvement in an anticoagulation clinic: development of a new treatment
      protocol.
AB  - We sought to improve patient outcomes and efficiency in our anticoagulation
      clinic through development of a new protocol for managing heart valve patients
      with subtherapeutic international normalized ratio (INR) tests. The new protocol
      standardized use of 1 anticoagulation agent while warfarin was retitrated,
      timelines for INR retesting, and target INR levels depending on the type of valve
      implanted. The new protocol provided significant improvements in patient care;
      however, outcomes for clinic operating efficiency were mixed.

PMID- 22157420
TI  - First rib fractures in abused infants: a report of three cases.
AB  - The authors describe 4 first rib fractures in 3 infants, highlighting the
      difficulty in detecting first rib fractures on skeletal survey. All 4 fractures
      were the result of physical abuse. A literature search does not find a case of
      first rib fracture in a healthy infant that is not the result of child abuse. The
      diagnosis of first rib fracture in an infant should prompt a thorough medical and
      social evaluation for child abuse.

PMID- 22157421
TI  - Validation of a modified pediatric early warning system score: a retrospective
      case-control study.
AB  - The Pediatric Early Warning System (PEWS) score may be useful for detection of
      deterioration in clinical condition. In this retrospective study, the cases were
      patients transferred to the pediatric intensive care unit (PICU), and controls
      were those not transferred to the PICU. The maximum PEWS score in both groups
      were analyzed using Mann-Whitney U test and receiver operating characteristic
      curve (ROC). The study population included 100 cases and 250 controls. There was
      no difference in the age of cases and controls (6.3 vs 6.3 years). The length of
      hospital stay (18.09 +/- 32 vs 3.93 +/- 2.9 days; P < .001) and the maximum PEWS
      score (2.95 +/- 1.5 vs 1.4 +/- 0.8) were significantly higher for the cases (P <
      .0001). The PEWS score area under the ROC was 0.81 (95% confidence interval =
      0.75-0.86). The sensitivity and specificity for a score 2.5 were 62% and 89%,
      respectively. The use of the modified PEWS score can help identify patients on
      wards who are at risk for deterioration.

PMID- 22157423
TI  - Interstitial lung disease as an unusual presenting symptom in juvenile
      dermatomyositis.

PMID- 22157422
TI  - Cholesterol curves to identify population norms by age and sex in healthy weight
      children.
AB  - OBJECTIVE: Develop clinically applicable charts of lipid values illustrating
      fluctuations throughout childhood and by sex among healthy weight children.
      METHODS: The National Health and Nutrition Examination Survey (1999-2008) was
      used to estimate total cholesterol, high-density lipoprotein (HDL), low-density
      lipoprotein (LDL), and triglycerides by age and sex in healthy weight children
      age 3 to 17 years. Using LMS procedures, the authors created smoothed curves
      demonstrating population-based 50th percentile for age and the 75th and 95th
      percentiles. RESULTS: The curves were based on 7681 children meeting inclusion
      criteria. Total cholesterol, HDL, and LDL demonstrated peaks at approximately 8
      to 12 years for boys. Similar peaks were evident for girls at slightly younger
      ages, approximately 7 to 11 years. Triglycerides showed peaks for girls, but
      values were similar across ages for boys. CONCLUSIONS: The use of fixed lipid
      value cutoffs in established guidelines regardless of age or sex likely mislabels
      many children as abnormal. The authors' charts may allow for a more nuanced
      interpretation based on population norms.

PMID- 22157424
TI  - Migratory polyarthritis in a child.

PMID- 22157425
TI  - Effect of routine mental health screening in a low-resource pediatric primary
      care population.
AB  - OBJECTIVE: Despite evidence for its feasibility, the usage of mental health
      screening in primary care practices with overburdened providers and few referral
      options remains unclear. This study explores the effects of routine screening on
      mental health problem identification and management in a low-resource setting.
      METHODS: Medical records of 5 to 12 year-old children presenting for well visits
      before and after screening was implemented were reviewed. Multivariate logistic
      regression was used to explore associations between study period and
      identification/management practices. Changes in the number of visits and wait
      times for a co-located referral service were assessed post hoc. RESULTS: Parents
      disclosed more mental health problems, and providers initiated more workups but
      referred fewer patients after screening was implemented. The proportion of new
      visits and wait times for the referral service did not change. CONCLUSIONS: Even
      in low-resource settings, screening may facilitate parental disclosure and
      increase clinical attention to mental health problems without overburdening
      referral services.

PMID- 22157426
TI  - Outpatient management of patients with bronchiolitis discharged home on oxygen: a
      survey of general pediatricians.
AB  - OBJECTIVE: To describe the experience of general pediatricians in weaning
      bronchiolitis patients, treated as outpatients, from oxygen. METHODS: The authors
      surveyed members of the American Academy of Pediatrics' Council on Community
      Pediatrics regarding management of outpatient oxygen for bronchiolitis. RESULTS:
      The survey had 214 (28.4%) responses from pediatricians, of whom 172 (80.3%)
      practiced outpatient pediatrics. Among those, 27 (15.7%) cared for bronchiolitis
      patients discharged on oxygen. Pediatricians managing home oxygen practiced at
      higher altitude (5000 vs 339 ft, P < .001). No clear weaning protocol was
      reported. Over half (61.5%) of the pediatricians managing home oxygen
      acknowledged difficulty in deciding when to stop oxygen. A median of 2
      (interquartile range [IQR] = 2-2) outpatient visits and 6 (IQR = 4-7) outpatient
      days on home oxygen were needed prior to oxygen discontinuation. CONCLUSION:
      Pediatricians are not routinely managing home oxygen for hypoxic bronchiolitis
      patients. Variable weaning process, difficulties in determining oxygen stoppage,
      multiple follow-up visits, and prolonged home oxygen usage highlight the need to
      evaluate the impact of this emerging practice.

PMID- 22157427
TI  - Invasive group A streptococcus infection presenting as purulent pericarditis with
      multiple splenic abscesses: case report and literature review.
AB  - Purulent pericarditis is a localized infection of the pericardium producing an
      effusion that is both microscopically and macroscopically purulent. Purulent
      pericarditis is most frequently caused by Staphylococcus, although rarely
      Streptococcus and other organisms are implicated. This article describes a case
      of invasive group A streptococcal disease presenting as purulent pericarditis
      with multiple splenic abscesses in a 4-year-old boy.

PMID- 22157428
TI  - A child with recurrent gross hematuria caused by the nutcracker syndrome: lessons
      learned.

PMID- 22157429
TI  - Acute onset vomiting in a toddler: an uncommon presentation of duodenal stenosis.

PMID- 22157430
TI  - Exergaming for health: a community-based pediatric weight management program
      using active video gaming.
AB  - OBJECTIVE: To evaluate the efficacy and feasibility of a multifaceted, community
      based weight intervention program for children using exergaming technology
      (activity-promoting video gaming). DESIGN AND METHODS: This is a prospective
      observational pilot study. Forty-eight children, between the ages of 8 and 16
      years, who are overweight or obese, enrolled in Exergaming for Health, a
      multidisciplinary weight management program, which used active video gaming.
      Primary outcome measures were change in body mass index (BMI) z scores. RESULTS:
      Most children (n = 40, 83%) completed the program and participated in outcome
      evaluations. The average BMI change was -0.48 kg/m(2) (SD = 0.93), P < .002 (BMI
      z-score change was -0.072, SD = 0.14, P < .0001). The average Global Self-Worth
      score improved, screen time and soda intake reduced, and exercise hours per week
      increased. CONCLUSIONS: The Exergaming for Health program may be an effective
      weight management intervention that is feasible with high participation rates. A
      larger randomized controlled trial is needed to confirm these results.

PMID- 22157432
TI  - The effects of visual and auditory cues on freezing of gait in patients with
      Parkinson disease.
AB  - OBJECTIVE: The aims of this study was to investigate the effects of visual and
      auditory cues on the freezing of gait in Parkinson disease patients (PDF)
      compared with Parkinson disease patients without freezing of gait (PDNF). DESIGN:
      Fifteen PDF, 10 PDNF, and 10 age-matched healthy volunteers were recruited.
      Subjects walked back and forth on a 7-m walkway under three different conditions:
      baseline condition without cues, with visual cues, and with auditory cues. Visual
      cues consisted of white stripes located along the walkway. For auditory cues, a
      metronome was used. Gait was analyzed using three-dimensional computerized
      analysis. RESULTS: In the PDF group, both visual and auditory cues significantly
      affected visuospatial and kinematic gait parameters. PDF group benefited more
      from visual cues than auditory cues. In the PDNF and healthy volunteer groups,
      visual cues significantly decreased patient velocity. Auditory cues affected some
      kinematic parameters on PDNF group. Compared among three groups, visual cues more
      positively affected the PDF group, and auditory cues more positively affected
      kinematic parameters in the PDNF group. CONCLUSIONS: This study suggests that
      gait training using visual and auditory cues can improve PDF patient gait and
      that auditory cues enhance gait in PDNF patients with hypokinetic gait patterns.

PMID- 22157433
TI  - Balance and mobility dysfunction and falls risk in older people with mild to
      moderate Alzheimer disease.
AB  - OBJECTIVE: This study aimed to identify the magnitude and type of balance and
      mobility impairments in people with Alzheimer disease by comparing their
      performance with that of older people without cognitive impairment. DESIGN:
      Twenty-five community-dwelling people with mild to moderate Alzheimer disease and
      a comparison group of 25 cognitively intact age- and sex-matched people completed
      a comprehensive balance and mobility assessment. This included computerized
      posturography measures of static and dynamic balance under various conditions,
      clinical balance, and mobility measures, and measures of falls and falls risk.
      RESULTS: The level of falls risk was higher in people with Alzheimer disease.
      Standing balance in people with Alzheimer disease was significantly impaired
      across a range of static and dynamic balance conditions. Activity level, gait,
      and mobility measures were also impaired, particularly turning and dual tasks.
      CONCLUSIONS: The findings of the study highlight the value of including balance
      screening as a routine component of early dementia assessment. This would allow
      for the early detection of balance dysfunction and the introduction of balance
      retraining before impairments progress to more advanced levels.

PMID- 22157434
TI  - Stroke-related changes in neuromuscular fatigue of the hip flexors and functional
      implications.
AB  - OBJECTIVE: The aim of this study was to compare stroke-related changes in hip
      flexor neuromuscular fatigue of the paretic leg during a sustained isometric
      submaximal contraction with those of the nonparetic leg and controls and to
      correlate fatigue with clinical measures of function. DESIGN: Hip torques were
      measured during a fatiguing hip flexion contraction at 20% of the hip flexion
      maximal voluntary contraction in the paretic and nonparetic legs of 13 people
      with chronic stroke and 10 age-matched controls. In addition, the participants
      with stroke performed a fatiguing contraction of the paretic leg at the absolute
      torque equivalent to 20% maximal voluntary contraction of the nonparetic leg and
      were tested for self-selected walking speed (10-m Walk Test) and balance (Berg).
      RESULTS: When matching the nonparetic target torque, the paretic hip flexors had
      a shorter time to task failure compared with the nonparetic leg and controls (P <
      0.05). The time to failure of the paretic leg was inversely correlated with the
      reduction of hip flexion maximal voluntary contraction torque. Self-selected
      walking speed was correlated with declines in torque and steadiness. Berg-Balance
      scores were inversely correlated with the force fluctuation amplitude.
      CONCLUSIONS: Fatigue and precision of contraction are correlated with walking
      function and balance after stroke.

PMID- 22157435
TI  - Stepping exercises improve muscle strength in the early postoperative phase after
      total hip arthroplasty: a retrospective study.
AB  - OBJECTIVE: This study aimed to evaluate the effect of stepping exercises in
      addition to conventional physical therapy on the recovery of muscle strength and
      walking speed after total hip arthroplasty. DESIGN: This was a retrospective
      study with 6 wks of follow-up care and evaluation. Patients (n = 30) undergoing
      primary total hip arthroplasty for hip osteoarthritis were divided into two
      groups based on whether stepping exercises were performed after surgery. The
      control group (n = 15) received supervised conventional physical therapy for 6
      wks. The stepping group (n = 15) performed stepping exercises with conventional
      physical therapy. Outcome measures were lower limb muscle strength and walking
      speed at 6 wks postoperatively. RESULTS: The stepping group showed significantly
      higher recovery of the hip abductor and the knee extensor muscle strengths on the
      involved side compared with the control group. There were no significant
      differences between the two groups in walking speed and hip extensor, hip flexor
      and knee flexor strength on the involved side. CONCLUSIONS: Our findings suggest
      that stepping exercises may be effective in facilitating the muscular recovery of
      the hip abductors and knee extensors in the early postoperative phase after total
      hip arthroplasty.

PMID- 22157436
TI  - Botulinum toxin a treatment in children with cerebral palsy: its effects on
      walking and energy expenditure.
AB  - OBJECTIVE: This study aimed to evaluate the effects of botulinum toxin A (BTX-A)
      treatment on energy expenditure and ambulation in children with cerebral palsy
      (CP) and to determine if energy expenditure measurement could be considered a
      useful tool for evaluating the effectiveness of BTX-A treatment for CP. DESIGN:
      The study included 16 pediatric CP patients with equinus deformity who were
      capable of walking without assistance (group with CP). The children with CP were
      administered BTX-A injections into the gastrocnemius muscle. All the children
      underwent three-dimensional gait analysis and energy expenditure measurement
      before injection and 8 wks after injection, the results of which were compared
      with those of children without CP (control group). RESULTS: After BTX-A
      treatment, oxygen consumption in the group with CP was significantly lower than
      at pretreatment and was similar to that in the control group (P > 0.05). In the
      group with CP, post-BTX-A treatment ankle joint dorsiflexion angle at initial
      contact, mid-stance, and mid-swing improved significantly (P < 0.05). CONCLUSION:
      BTX-A injected into the gastrocnemius muscle in children with CP not only reduced
      spasticity and improved ankle range of motion and walking pattern but also
      reduced energy consumption, resulting in functional improvement. Energy
      expenditure measurement can be considered an objective quantitative tool for
      clinical evaluation of the functional outcome of therapeutic interventions such
      as BTX-A.

PMID- 22157437
TI  - Tracheostomy management skills competency in physical medicine and rehabilitation
      residents: a method for development and assessment.
AB  - This educational unit was developed to instruct physical medicine and
      rehabilitation residents on tracheostomy management in non-ventilator-dependent
      patients and to implement an objective assessment format to measure the
      attainment of these skills. Thirty-one subjects participated in a 2-day didactic
      and hands-on workshop supervised by an attending physiatrist, certified speech
      pathologists, and registered nurses. Assessment tools developed for this program
      address the basic competencies outlined by the Accreditation Council for Graduate
      Medical Education. To test the success of the standardized educational module,
      data have been collected on an ongoing basis for a period of 6 yrs. A before-and
      after multiple-choice written examination, as well as simulated patient
      encounters consisting of eight segments divided into four stations, was used to
      assess knowledge acquisition and skill achievement. Before instruction, none of
      the 31 participants were able to perform appropriate tracheostomy care. After the
      workshop, 31 of 31 (100%) successfully demonstrated clinical proficiency in every
      segment of the evaluation element of the educational module. Furthermore, a
      significant increase in knowledge was observed in the multiple-choice examination
      from pretest to posttest (pretest, 52.7%; posttest, 84.5%). Participation in this
      module resulted in substantial acquisition of knowledge and skills regarding
      tracheostomy management for physical medicine and rehabilitation residents.

PMID- 22157438
TI  - The role of ultrasonography in the differential diagnosis and treatment of tennis
      elbow.

PMID- 22157439
TI  - Recent advances in Helicobacter pylori pathogenesis.
AB  - PURPOSE OF REVIEW: Helicobacter pylori is implicated in numerous gastric
      pathologies; however, the prevalence of infection is declining in developed
      countries. Therefore, it is important to understand the complex mechanism of its
      interaction with the host and how the changing epidemiology of infection may
      impact on disease. In this review, we systemically revisit the major novel
      discoveries of the last year relating to H. pylori disease pathogenesis. RECENT
      FINDINGS: Novel pathways have been implicated in H. pylori cytotoxin-associated
      gene (CagA) mediated carcinogenesis, highlighting the aberrant regulation of
      proliferation and apoptosis. Furthermore, the human microbiome was implicated as
      having a key role in H. pylori-related disease development. Several studies have
      begun to delineate the mechanisms behind the epidemiologically inverse
      correlation of H. pylori infection with asthma and inflammatory bowel disease.
      SUMMARY: The recent findings enable researchers to focus on novel and previously
      unsuspected mechanisms in the development of disease, and prompt further research
      into possible therapeutic approaches. The potential beneficial aspects of H.
      pylori colonization and the role bacterial flora play in promoting disease have
      yet to be elucidated, but promise to have a great impact on patient care.

PMID- 22157440
TI  - Current world literature.

PMID- 22157442
TI  - Longitudinal effects of prenatal cocaine use on mother-child interactions at ages
      3 and 5 years.
AB  - OBJECTIVE: To assess the effect of maternal prenatal and past-year cocaine use on
      mother-child interactions across preschool years. METHODS: The sample is drawn
      from the Miami Prenatal Cocaine Study, a longitudinal follow-up of prenatal
      cocaine exposure (PCE) in a large cohort of African-American infants
      prospectively enrolled at birth. Analyses are based on the 366 children (168 PCE
      and 198 non-cocaine-exposed) in the care of their biological mothers and with
      completed mother-child interaction measures at the 3- and/or 5-year assessments.
      Videotaped interactions were coded using a modified Egeland Teaching Task scheme.
      Generalized linear models with a generalized estimating equations approach were
      used to evaluate the effect of PCE on the overall quality of maternal-child
      interaction, measured by the Egeland total score at both study visits, and on the
      individual Egeland subscales at the 5-year visit, while adjusting for other
      suspected influences on interactions. RESULTS: PCE dyads demonstrated less
      optimal overall mother-child interactions compared with non-cocaine-exposed
      dyads. The estimated PCE-associated difference did not shift appreciably with
      statistical adjustment for child sex, child age at examination, or other birth
      covariates. PCE dyads with past-year maternal cocaine use had significantly lower
      Egeland summary scores compared with children with neither exposure. In subscale
      analyses, PCE was most strongly associated with greater maternal intrusiveness
      and boundary dissolution at the 5-year visit. CONCLUSIONS: Prenatal and past-year
      maternal cocaine use seems to be associated with poorer quality in mother-child
      interaction during early childhood. These dynamics should be considered when
      examining the association between PCE and child cognitive, behavioral, and
      academic outcomes.

PMID- 22157443
TI  - Interpreting parents' concerns about their children's development with the
      Parents Evaluation of Developmental Status: culture matters.
AB  - OBJECTIVE: This study explored the potential roles and utility of the Parents
      Evaluation of Developmental Status (PEDS) to screen children for developmental
      delays in a Southeast Asian clinical sample of preschool children. The PEDS is a
      10-item questionnaire instrument used in pediatric settings for reporting
      parents' concerns for their children's development, learning, and behavior.
      Clinicians use it to make decisions about clinical pathways for high-, moderate-,
      and low-risk categories of concerns, but its utility in cross-cultural contexts
      has not been well documented. METHODS: Participants in this study were 1806
      parents, teachers, and child care workers of preschool children in Singapore. Of
      these, 47.2% were English speaking, 21.2% were Mandarin Chinese speaking, and
      31.6% were Malay speaking. PEDS was translated into Chinese and Malay for parents
      using these languages predominantly. RESULTS: Only parent results were analyzed.
      The reporting of significant parental concern was considerably higher than US
      norms and Australian pilot figures when western cutoff scores were applied. When
      cutoff scores were adjusted, similar patterns of reporting of high, medium, and
      low risk for disability could be captured. CONCLUSIONS: Parents' interpretation
      of the concept of "concern" varies across language and culture. Findings
      highlight the importance of evaluating a screening tool's use in local contexts
      before its widespread implementation to yield clinically meaningful results.

PMID- 22157444
TI  - Setting research priorities in anaesthesia.

PMID- 22157445
TI  - Paediatric cardiomyopathy and anaesthesia.
AB  - 'Cardiomyopathy' (CM) is defined by the World Health Organization as 'a disease
      of the myocardium associated with cardiac dysfunction'. In a child, it is
      associated with a significant risk for anaesthesia. In addition, cardiac arrest
      under anaesthesia has been attributed to an undiagnosed CM. Care of these
      patients is complicated by the fact that there are several different forms of CM
      that have differing anaesthesia management goals, aimed at maintaining the
      patient's baseline haemodynamic variables of preload, heart rate, contractility,
      and afterload. With the emergence of new diagnostic tools, together with advances
      in cardiac imaging and improved treatment modalities (such as ventricular assist
      devices), the anaesthetic management of a child with a CM is evolving. This
      review describes the different forms of the disease in terms of pathology,
      aetiology, and clinical presentation. Dilated, hypertrophic, and restrictive CM
      are the most common forms. We examine recent advances in therapy, including the
      management of severe end-stage disease, while highlighting the specific
      anaesthetic considerations for children with each type of CM.

PMID- 22157446
TI  - Adverse event reporting tool to standardize the reporting and tracking of adverse
      events during procedural sedation: a consensus document from the World SIVA
      International Sedation Task Force.
AB  - Currently, there are no established definitions or terminology for sedation
      related adverse events (AEs). With clear terminology and definitions, sedation
      events may be accurately identified and tracked, providing a benchmark for
      defining the occurrence of AEs, ranging from minimal to severe. This terminology
      could apply to sedation performed in any location and by any provider. We present
      a consensus document from the International Sedation Task Force (ISTF) of the
      World Society of Intravenous Anaesthesia (World SIVA). The ISTF is composed of
      adult and paediatric sedation practitioners from multiple disciplines throughout
      the world.

PMID- 22157447
TI  - National Institute of Academic Anaesthesia research priority setting exercise.
AB  - BACKGROUND: Formal research priority setting is a recognized way of identifying
      important clinical research questions and promoting these as topics for
      commissioned research. This paper describes a research priority setting exercise
      conducted by the National Institute of Academic Anaesthesia (NIAA). METHODS:
      Possible research questions were identified from a questionnaire sent to holders
      of the Final Fellowship in Anaesthesia in Great Britain and Ireland and to lay
      representatives. The responses to the first questionnaire were collated to
      produce a list of potential research questions which were then sent to the same
      constituency for scoring. The results of this scoring process were considered by
      an expert panel and statements of research need generated for selected questions.
      The questions from the first round were also reviewed with the help of
      representatives of NIHR Evaluation, Trials and Studies Coordinating Centre
      (NETSCC). RESULTS: For the first questionnaire, 308 responses with 447
      suggestions for research were received. A total of 15 questions were included in
      the second questionnaire, for which 2226 responses were received. The expert
      panel identified five questions for prioritization. A further nine were
      identified from discussions with representatives of NETSCC. CONCLUSIONS: A total
      of 14 research priorities were identified by the exercise, two of which have been
      submitted to the NIHR Health Technology Assessment (HTA) programme as statements
      of research need. Potential funding streams for the remaining questions are being
      sought. We discuss some implications of this exercise for research strategy in
      the speciality.

PMID- 22157448
TI  - Hydroxyethyl starch in patients with trauma.

PMID- 22157450
TI  - Adding dexamethasone to peripheral nerve blocks can give better postoperative
      analgesia.

PMID- 22157452
TI  - Ultrasound-guided supraclavicular approach to the subclavian vein in infants and
      children.

PMID- 22157454
TI  - Minimal mortality benefit with early surgery for high-risk fractured hip
      patients.

PMID- 22157456
TI  - Bibliometrics of anaesthesia researchers in the UK.

PMID- 22157458
TI  - Increase in cerebral metabolites during induction of propofol anaesthesia.

PMID- 22157459
TI  - Anaemia tolerance: bridging with intravenous ferric carboxymaltose in a patient
      with acute post-haemorrhagic anaemia.

PMID- 22157460
TI  - Interference with BISTM values from a forced-air warming device.

PMID- 22157461
TI  - Nebulized magnesium for prevention of postoperative sore throat.

PMID- 22157462
TI  - Is age a predictor of mortality in a UK medical high dependency unit?

PMID- 22157466
TI  - Career histories and managerial performance of health care chief executive
      officers: an empirical study in the Italian National Health Service.
AB  - BACKGROUND: Organizational studies widely acknowledge the importance of the
      relationship between CEO's career histories and managerial performance. Although
      the health care management literature largely explores the role of CEOs, whether
      and how top managers' career histories affect their own performance remains still
      unknown in this industry. PURPOSE: The aim of this study was to investigate the
      career histories of health care CEOs and to explore their impact on managerial
      performance. METHODOLOGY: Primary data were collected from a sample of 124 CEOs
      leading health care organizations in the Italian National Health Service in 2008.
      Biographic data were accessed to gather information about relevant CEOs'
      demographics and their career histories. The relevance of CEOs' prior experience
      was considered, taking into account the prominence of health care organizations
      in which they passed through in their career histories. Regression analyses were
      employed to assess the impact of CEOs' career histories on their managerial
      performance. FINDINGS: Top managers already appointed as CEOs were more likely to
      achieve higher levels of performance. Careers with long tenure within the
      National Health Service appear to increase managerial performance. Those CEOs who
      accumulated prior experience in a large number of health care structures and who
      spent time working at the most prominent hospitals were also more likely to
      achieve higher levels of managerial performance. IMPLICATIONS: In health care, a
      CEO's career history does impact his or her managerial performance. Specifically,
      patterns of career that imply higher mobility across health care organizations
      are important. Although interorganizational mobility is significant for CEO
      performance, the same does not hold for mobility across industries. These
      findings contribute to the current debate about the need for management
      renovation within health care organizations.

PMID- 22157467
TI  - Differences between rheumatologists and other internists regarding diagnosis and
      treatment of systemic lupus erythematosus.
AB  - OBJECTIVES: To compare the diagnostics and treatment of SLE patients in the care
      of rheumatologists with patients in the care of other specialities within a
      geographically complete cohort. METHODS: Nine different sources were used to
      identify SLE patients resident in Oslo between 1999 and 2008. Only SLE patients
      fulfilling four or more of the updated 1997 ACR criteria were included. Data were
      extracted from medical records. The patients were classified into three groups
      according to each patient's responsible doctor's speciality. RESULTS: A total of
      325 SLE patients were included in the study. Of these, 227 had solely been in the
      care of rheumatologists (rheumatology group), 34 had solely been in the care of
      nephrologists, haematologists or infectious disease specialists (non-rheumatology
      group) and 64 had been in the care of both rheumatologists and other specialists
      (multidisciplinary group). Even though patients in the non-rheumatology group and
      multidisciplinary group showed similar disease characteristics, patients in the
      non-rheumatology group were less often tested for aPLs (68 vs 94%; P = 0.001) and
      less often treated with HCQ (12 vs 78%; P < 0.001). CONCLUSIONS: In contrast to
      rheumatologists, non-rheumatologists do not routinely test all SLE patients for
      aPLs, and rarely prescribe HCQ. These findings indicate that more communication
      between different specialists caring for SLE is needed, and highlights an area in
      need of agreement.

PMID- 22157468
TI  - Non-infectious pulmonary toxicity of rituximab: a systematic review.
AB  - OBJECTIVE: Rituximab (RTX), a B-cell depleting mAb, has been reported to cause
      pulmonary toxicity in many patients. As the use of this biologic is increasing,
      we have undertaken a systematic review of the literature to gauge the nature and
      extent of non-infection-related RTX-induced lung disease. METHODS: A systematic
      literature review was undertaken to document all reported cases of RTX-associated
      interstitial lung disease (RTX-ILD), evaluating the epidemiological, clinical,
      radiological, histopathological, laboratory and management data from the
      available primary sources. The search was conducted using PubMed, the Cochrane
      Library and EMBASE up to June 2010 using the terms RTX in the advanced search
      option without limitations and all relevant publications reviewed manually. In
      addition, unpublished data from the Food and Drug Administration, the European
      Medicines Agency and the manufacturer (Roche) were evaluated to complement this
      search. Identified articles were included if they displayed a potential
      relationship between the administration of RTX and ILD following exclusion of
      other likely causes. RESULTS: A total of 121 cases of potential RTX-ILD were
      identified from 21 clinical studies/trials, 30 case reports and 10 case series.
      The most common indication for RTX was diffuse large B-cell lymphoma. RTX-ILD
      occurred more frequently in male patients and was most common during the fifth
      and sixth decades of life. In most cases, RTX was part of combination
      chemotherapy, but in 30 (24.7%) cases it was given as monotherapy. The mean and
      median number of cycles of RTX before disease onset was four, but cases following
      the first cycle or as late as the 12th cycle were also identified. The mean time
      of onset, from the last RTX infusion until symptom development or relevant
      abnormal radiological change was 30 days (range 0-158 days). Abnormal
      radiological findings were similar in all patients, with diffuse bilateral lung
      infiltrates apparent on chest radiographs and/or thoracic CT. Hypoxaemia was seen
      in all cases and pulmonary function tests were uniformly abnormal with a
      characteristic diffusion capacity deficit and restrictive ventilatory pattern.
      RTX-ILD was fatal in 18 cases. CONCLUSION: ILD is a rare but potentially fatal
      complication of RTX therapy. This diagnosis should be considered in any patient
      who develops respiratory symptoms or new radiographic changes while receiving
      this biologic agent.

PMID- 22157469
TI  - Patients with psoriatic arthritis have worse quality of life than those with
      psoriasis alone.
AB  - OBJECTIVE: PsA is an inflammatory arthritis present in ~30% of people with
      psoriasis (PsC). Both conditions have a significant impact on quality of life
      (QoL). Our objective was to test the hypothesis that people with PsA have poorer
      QoL than patients with PsC because of the added burden of arthritis, age and
      comorbidities. METHODS: Consecutive patients with PsA (CASPAR criteria) and PsC
      were approached to participate in this study. Patients with PsC were examined by
      a rheumatologist using a standardized protocol to exclude PsA. Patients completed
      the HAQ, Medical Outcome Study 36-item Short Form Health Survey, Dermatology Life
      Quality Index (DLQI), EuroQoL 5 domains (EQ-5D) and Fatigue Severity Scale (FSS).
      Mean scores were compared and multivariate analyses were conducted to compare the
      QoL measures between the two patient groups. RESULTS: Two hundred and one
      patients with PsC and 201 patients with PsA were studied. A significant decrease
      in QoL for patients with PsA compared with those with PsC was identified by all
      questionnaires except for the DLQI. This skin-specific questionnaire revealed a
      lower QoL in patients with PsC. Multivariate analyses for each QoL measure
      confirmed the results of these analyses. After adjusting for age, sex, duration
      of PsC, comorbidities, DMARDs and biologic therapy, HAQ and DLQI were
      independently associated with PsA in a logistic regression. CONCLUSION: Patients
      with PsA have a poorer QoL compared with those with PsC as measured by all
      questionnaires except the DLQI.

PMID- 22157470
TI  - A tradition of learning and international exchange in interventional cardiology:
      a speciality with a "whole-world" embrace.

PMID- 22157471
TI  - Percutaneous coronary interventions in saphenous vein grafts: the more things
      change, the more they stay the same.

PMID- 22157472
TI  - Complications with a happy ending.

PMID- 22157473
TI  - Rayonnement....

PMID- 22157474
TI  - What is the evidence allowing us to state that transcatheter aortic valve
      replacement via the femoral artery is a more attractive option compared to
      transapical valve replacement?

PMID- 22157476
TI  - The impact of fractional flow reserve measurement on clinical outcomes after
      transradial coronary stenting.
AB  - AIMS: Fractional flow reserve (FFR) >=0.96 after stenting correlates well with an
      optimal stent expansion, but outcomes based on FFR after drug eluting stents
      (DES) have not been studied. This study sought to investigate the proportion of
      patients in whom an FFR >=0.96 can be achieved after transradial stenting using
      primarily DES and to determine outcomes based on a post-stent FFR >=0.96 vs. an
      FFR<0.96. METHODS AND RESULTS: A total of 66 patients with single-vessel disease
      and FFR<0.75 underwent transradial stenting. After stenting, FFR was <0.96 in 34
      patients and there was a hyperaemic trans-stent gradient across the edges of
      stent in five patients; after high-pressure balloon inflation, FFR increased to
      >=0.96 in three patients and an FFR >=0.96 was achieved in 35 patients (53%,
      group 1), but FFR remained <0.96 in 31 patients (47%, group 2). There was no
      correlation between FFR and minimum lumen diameter in group 1 or group 2 (r=0.03;
      p=0.72 and r=0.02; p=0.22, respectively). The 24-month event-free survival
      estimate defined as freedom from death, MI, and target vessel revascularisation
      (PCI or CABG) was significantly greater in group 1 than in group 2 (94% versus
      72%, respectively; p=0.02). CONCLUSIONS: After transradial stenting with
      predominately DES, an FFR >=0.96 was achieved in only 53% of patients and event
      rates among patients with a post-stent FFR >=0.96 were significantly lower than
      those with an FFR<0.96.

PMID- 22157475
TI  - Radial access in patients with ST-segment elevation myocardial infarction
      undergoing primary angioplasty in acute myocardial infarction: the HORIZONS-AMI
      trial.
AB  - AIMS: We sought to determine whether a transradial (TR) approach compared with a
      transfemoral (TF) approach was associated with improved clinical outcomes in
      patients with ST-segment elevation myocardial infarction (STEMI) undergoing
      primary percutaneous coronary intervention (PCI) in a post hoc analysis of the
      HORIZONS-AMI trial. There is a paucity of data comparing the TR approach with the
      TF approach in patients with STEMI treated with primary PCI and contemporary
      anticoagulant regimens. METHODS AND RESULTS: In HORIZONS-AMI, primary PCI for
      STEMI was performed in 3,340 patients, either by the TR (n=200) or TF approach
      (n=3,134). Endpoints included the 30-day and one-year rates of major adverse
      cardiovascular events (MACE: death, reinfarction, stroke or target vessel
      revascularisation), non CABG-related major bleeding, and net adverse clinical
      events (NACE: MACE or major bleeding). TR compared to TF access was associated
      with significantly lower 30-day rates of composite death or reinfarction (1.0%
      vs. 4.3%, OR 0.23, 95% CI [0.06,0.94], p=0.02), non CABG-related major bleeding
      (3.5% vs. 7.6%, OR 0.45, 95% CI [0.21,0.95], p=0.03), MACE (2.0% vs. 5.6%, OR
      0.35, 95% CI [0.13,0.95], p=0.02), and NACE (5.0% vs. 11.6%,OR 0.42, 95% CI
      [0.22,0.78], p<0.01). At one year, the TR group still had significantly reduced
      rates of death or reinfarction (4.0% vs. 7.8%, OR 0.51, 95% CI [0.25,1.02],
      p=0.05), non CABG-related major bleeding (3.5% vs. 8.1%, OR 0.42, 95% CI
      [0.20,0.89], p=0.02), MACE (6.0% vs. 12.4%, OR 0.47, 95% CI [0.26,0.83], p<0.01)
      and NACE (8.5% vs. 17.8%, OR 0.45, 95% CI [0.28,0.74], p<0.001). By multivariable
      analysis, TR access was an independent predictor of freedom from MACE and NACE at
      30 days and one year. CONCLUSIONS: In patients with STEMI undergoing primary PCI
      with contemporary anticoagulation regimens in the HORIZONS-AMI trial, a TR
      compared with a TF approach was associated with reduced major bleeding and
      improved event-free survival.

PMID- 22157477
TI  - Radial artery access for above the knee angioplasty: a feasibility study.
AB  - AIMS: Lower limb angioplasty is usually performed by transfemoral access despite
      the risk of local complications. Transradial access (TRA) has gained acceptance
      for coronary interventions. The aim of this study was to evaluate the feasibility
      and safety of TRA for above the knee (ATK) angioplasty. METHODS AND RESULTS:
      Twenty-five consecutive patients (eight females; mean age 72, range 55-85 years;
      seven symptomatic for critical limb ischaemia, 18 for claudication) underwent ATK
      angioplasty by left (19) or right (6) TRA. A total of 32 lesions were addressed;
      16 stents were positioned in 12 patients with an overall success rate of 81%, and
      a success rate of 38% on occlusions and of 96% on stenoses. The overall success
      rate on the 16 supra-inguinal lesions was 81%, (success rate 60% on occlusions
      and 91% on stenoses). The overall success rate on the 16 infra-inguinal lesions
      was 81%, (success rate 0% on occlusions and 100% on stenoses). Any haemorrhagic
      complications or local complications needing surgery were observed in the cohort
      of patients. CONCLUSIONS: TRA can represent a feasible and safe alternative for
      ATK angioplasty in case of difficult femoral access.

PMID- 22157478
TI  - Comparison of novel 6.5 Fr sheathless guiding catheters versus 5 Fr guiding
      catheters for transradial coronary intervention.
AB  - AIMS: To assess the safety and efficacy of a novel sheathless (SH) 6.5 Fr
      (French) hydrophilic-coated guiding catheter (GC) compared to the standard 5 Fr
      GCs in transradial coronary interventions (TRI). METHODS AND RESULTS: Patients
      undergoing TRI with 6.5 Fr SH or 5 Fr GCs were included. Baseline characteristics
      and in-hospital outcomes were recorded. Primary endpoints were procedural success
      and presence of radial pulse at discharge. Secondary endpoints were successful GC
      support, in-hospital adverse events, access-site complications, procedural
      duration and contrast load. There were 269 patients with 146 procedures in each
      group. The SH GC group had more non-ST elevation MI, in-stent restenosis, high
      risk and bifurcation lesions. Procedural success in both arms was 95.2%. One
      patient in each group (0.7%) experienced radial artery occlusion (RAO) after TRI,
      without clinical sequelae. One access-site haematoma and one minor stroke
      occurred in the 5 Fr group (none in the SH group, both p=ns). Mean procedure time
      (52+/-21 vs. 45+/-21 minutes, p=0.004) and contrast load (160+/-45 ml vs. 140+/
      45 ml, p=0.003) were greater in the SH group. CONCLUSIONS: Both 6.5 Fr SH GCs and
      5 Fr GCs achieved high procedural TRI success with low RAO rates. The SH GC
      eliminated the disadvantages of the 5 Fr GC whilst maintaining the advantage of
      low RAO rates, and may become the GC of choice in TRI.

PMID- 22157479
TI  - The physiological significance of coronary aneurysms in Kawasaki disease.
AB  - AIMS: A coronary aneurysm is one of the most frequent complications of Kawasaki
      disease, and yet there is little information concerning the haemodynamic
      abnormality influenced by the existence of a coronary aneurysm. When blood flow
      passes through an aneurysm, the turbulence that then occurs means that part of
      the initial energy is lost, and that energy loss could cause a drop in pressure,
      such as when passing through a stenotic lesion. The aim of this study is to prove
      the hypothesis that a giant aneurysm haemodynamically acts in a manner similar to
      that of stenosis. METHODS AND RESULTS: The study population consisted of 47
      patients with a simple coronary aneurysm after Kawasaki disease. Fractional flow
      reserve was measured in 32 coronary aneurysms. The fractional flow reserve in non
      giant aneurysms was 0.95+/-0.03 and 0.90+/-0.03 in giant aneurysms (p=0.0004).
      CONCLUSIONS: The present data demonstrated that the coronary aneurysm could give
      rise to a small decline of pressure along the artery. Since no aneurysm
      demonstrated a fractional flow reserve under 0.75, a simple aneurysm would not
      cause coronary ischaemia by itself. However, it could trigger a coronary
      ischaemia in case of multiple coronary aneurysms and a coronary aneurysm with
      mild stenosis.

PMID- 22157480
TI  - Paclitaxel-eluting stents reduce neointimal hyperplasia compared to bare metal
      stents in saphenous vein grafts: intravascular ultrasonography analysis of the
      SOS (Stenting of Saphenous Vein Grafts) trial.
AB  - AIMS: To compare the intravascular ultrasonography (IVUS) findings between
      saphenous vein grafts (SVG) treated with paclitaxel-eluting stents (PES) vs. bare
      metal stents (BMS) in the Stenting Of Saphenous Vein Grafts (SOS) trial. METHODS
      AND RESULTS: Of the 80 SOS trial patients, 38 had both baseline and follow-up
      IVUS examination and were included in this substudy: 17 patients received 28 BMS
      in 26 lesions and 21 patients received 30 PES in 28 lesions. Quantitative IVUS
      analysis was performed to determine the volume of in-stent neointimal hyperplasia
      (NIH) - defined as the difference between stent volume and lumen volume in the
      stented segments. Baseline characteristics were similar between patients who did
      and did not undergo baseline and follow-up IVUS. Patients receiving BMS and PES
      had similar stent and lumen volumes immediately after stenting. At 12-month
      follow-up, compared to BMS, PES-treated lesions had significantly less NIH volume
      (3.4 vs. 21.9 mm3, p<0.001) and neointima hyperplasia progression (1.6 vs. 17.1
      mm3, p<0.001). No significant differences were seen in the 5 mm segment proximal
      and distal to the stent. CONCLUSIONS: Compared to BMS, use of PES in SVG lesions
      is associated with significantly lower NIH formation, which may help explain the
      improved clinical outcomes with PES in these lesions.

PMID- 22157481
TI  - Filter no-reflow during percutaneous coronary intervention of saphenous vein
      grafts: incidence, predictors and effect of the type of protection device.
AB  - AIMS: To assess the main predictors and significance of filter no-reflow (FNR) in
      protected saphenous vein graft (SVG) percutaneous coronary intervention (PCI) and
      the effect of two different filter-based devices on FNR incidence. The phenomenon
      of FNR has been described as a transient impairment of blood flow due to debris
      plugging of a filter-based device used to shield the distal microvasculature
      during SVG PCI. METHODS AND RESULTS: Fifty consecutive patients treated with SVG
      PCI were enrolled, using two different filter-based devices (FilterWire EZTM
      [Boston Scientific, Natick, MA, USA] and SpiderRX(r) [Ev3, Plymouth, MN, USA]).
      We evaluated: 1) the value of clinical and angiographic variables for predicting
      FNR including the recently-described "degeneration score" (DS); 2) the predictive
      value of FNR for post-procedural (type IVa) myocardial infarction (MI); 3) the
      effect of filter type on incidence of FNR. FNR was observed in 30% of patients
      and was predicted by a higher DS at baseline (2.1+/-0.9 vs. 1.4+/-0.8, p=0.02,
      respectively) as well as by the type of filter used (54% vs. 23% in SpiderFX and
      FilterWire EZ, respectively, p=0.04). However, at multivariate analysis DS was
      the only independent predictor of FNR (OR 2.47, CI 95% 1.06-5.76, p=0.04). Graft
      age and FNR were found to be independent predictors of type IVa MI (OR 1.28;
      CI%E2%80%AF95% 1.01-1.64, p=0.04 and OR 15.69; CI%E2%80%AF95% 2.12-116.39,
      p=0.007, respectively). CONCLUSIONS: FNR is a common complication of protected
      SVG stenting. FNR occurs mainly in grafts with a high degeneration score, and the
      presence of FNR predicts post-procedural myocardial infarction.

PMID- 22157482
TI  - Outcomes in patients undergoing multivessel percutaneous coronary intervention
      using sirolimus-eluting stents: a report from the e-SELECT registry.
AB  - AIMS: Performing percutaneous coronary intervention (PCI) to multiple coronary
      lesions during the same procedure has potential economic and social advantages.
      However comprehensive outcome data of real world practice in a large population
      is limited. We aimed to compare short- and long-term outcomes between patients
      with multivessel coronary artery disease who either underwent single- or
      multivessel PCI within the e-SELECT registry. METHODS AND RESULTS: The e-SELECT
      registry combines data collected at 320 medical centres in 56 countries where
      patients received CYPHER Select(r) or CYPHER Select(r) Plus sirolimus-eluting
      stent (SES). Rates of myocardial infarction and major adverse cardiac event
      (MACE) (defined as any death, myocardial infarction or target lesion
      revascularisation) were compared between patients undergoing single-vessel versus
      multivessel PCI. A total of 15,147 patients who satisfied the inclusion criteria
      were included in the e-SELECT registry. Two thousand two hundred and seventy
      eight (2,278) subjects (15%) underwent multivessel PCI and 12,869 (85%) had
      single-vessel PCI. The mean age was higher in the multivessel PCI group (63 vs.
      62 years, p<0.001) and there was a higher prevalence of diabetes mellitus (32.4
      vs. 30.0%, p=0.02). Lesions were more complex in the single-PCI group while pre-
      and post-dilatation were less common in the multivessel PCI group. Myocardial
      infarction within the first 30 days post PCI was more common in the multivessel
      PCI group (1.9 vs. 0.8%, p<0.001) and most of the infarctions were periprocedural
      (1.3 vs. 0.6%, p=0.001). Mortality and myocardial infarction at one-year were
      higher in the multivessel PCI group resulting in a significantly higher MACE (6.1
      vs. 4.6%, p=0.005). CONCLUSIONS: Overall procedural and one year outcomes were
      excellent for both single- and multivessel procedures. However despite lower
      lesion complexity, performing multivessel PCI was associated with higher rates of
      periprocedural myocardial infarction and MACE when compared to single-vessel PCI
      in the e-SELECT registry.

PMID- 22157483
TI  - How should I treat a patient with left main disease and a totally occluded left
      anterior descending artery with a diseased saphenous venous graft?
AB  - BACKGROUND: A 60-year-old man with history of coronary bypass surgery in 2000
      with three saphenous venous grafts (SVG) to left anterior descending artery
      (LAD), diagonal and obtuse marginal branches, presented by worsening chest
      tightness of one month duration. He had a clinical history of hypertension,
      dyslipidaemia and chronic renal impairment. INVESTIGATION: Physical examination,
      electrocardiography, laboratory tests, echocardiography and coronary angiography.
      DIAGNOSIS: Significant aorto-ostial stenosis of the SVG to LAD, left main
      stenosis, chronic total occlusion of LAD from its origin and significant stenosis
      of the mid portion of left circumflex artery. TREATMENT: Percutaneous
      intervention re-do bypass surgery, dual anti-platelet therapy.

PMID- 22157484
TI  - Tools & techniques: Alcohol septal ablation for hypertrophic cardiomyopathy.

PMID- 22157485
TI  - A drug-eluting stent, accidentally removed as late as 11/2 years after
      implantation.

PMID- 22157486
TI  - Endovascular extraction of a coronary stent: resolution of a cathlab nightmare.

PMID- 22157487
TI  - Evidence-based nursing innovations.

PMID- 22157488
TI  - Nurse-led change: a statewide multidisciplinary collaboration targeting intensive
      care unit delirium.
AB  - For more than a decade, research has demonstrated both the widespread prevalence
      and negative outcomes associated with intensive care unit delirium. Hospitals
      are, therefore, being called to institute evidence-based protocols to prevent and
      manage its occurrence. Integrating evidence-based practice into bedside care can
      be a challenge. Having information ready and accessible is essential to
      implementing successful change. The state of Michigan, through the Michigan
      Health and Hospital Association Keystone Center, has historically gathered
      evidence and formulated processes to facilitate evidence implementation in
      statewide intensive care units. Toolkits have been developed to facilitate the
      spread of information and are used as a starting point for sites. This approach
      has been proven successful in reduction of ventilator-associated pneumonias and
      catheter-related blood stream infections, while in partnership with Johns Hopkins
      University. The purpose of this article is to describe the creation of evidence
      based toolkits used to facilitate successful statewide changes in practice using
      an interprofessional team including nurses, physicians, and pharmacists. The
      content reflects a step-wise approach to not only engage and educate staff, but
      also strategies to execute and evaluate the effectiveness.

PMID- 22157489
TI  - A systematic approach to improving medication safety in a pediatric intensive
      care unit.
AB  - Safety and quality improvement are major issues in children's hospitals.
      Improving pediatric medication safety often takes on a larger role in pediatric
      units than in adult units due to the larger size differences and dose ranges
      found in a pediatric intensive care unit. This article reviews the literature and
      our own experience at the CS Mott Children's Hospital, University of Michigan, to
      improve medication safety. The issues identified include (1) an effective
      pediatric medication safety governance structure within a larger hospital, (2)
      practice standardization strategies for physicians, nurses, and pharmacists, (3)
      use of pharmacy technicians as unit medication managers, which reduces medication
      costs and decreases nursing time spent hunting for medications, and (4) methods
      to improve the safety culture in a pediatric intensive care unit.

PMID- 22157490
TI  - Advanced ventilator modes and techniques.
AB  - In addition to improving gas exchange by mechanical ventilation, minimizing
      iatrogenic lung injury and making the patient comfortable are important goals.
      This article reviews advanced ventilator modes and techniques that might help to
      accomplish these goals. Small tidal volumes (VT) and low ventilation pressure
      minimize ventilator-induced lung injury. Airway pressure release ventilation and
      high-frequency oscillatory ventilation may provide lung-protective ventilation in
      certain patients with refractory hypoxemia. Adaptive support ventilation (ASV)
      automatically adjusts VT and rate on the basis of the patient's respiratory
      mechanics to provide "safe" settings. When ventilator output does not match
      patient respiratory center timing, patient-ventilator asynchrony occurs.
      Proportional assist ventilation and neutrally adjusted ventilatory assist are
      unique modes of ventilation that provide ventilatory support in direct proportion
      to patient effort and therefore may be able to better match patient need and
      improve comfort. Weaning protocols reduce duration of ventilation and intensive
      care unit stay. Certain ventilator modes purport to automate part of the
      ventilator discontinuance process. The ASV progressively reduces support as the
      patient's lung condition improves, while SmartCare/pressure support (Drager,
      Lubeck, Germany) reduces support and then initiates a spontaneous breathing
      trial. Further research is required to determine the proper place these new modes
      have in the intensive care unit.

PMID- 22157491
TI  - Expanded resources through utilization of a primary care giver extracorporeal
      membrane oxygenation model.
AB  - Extracorporeal membrane oxygenation (ECMO) is a long-term extracorporeal support
      for critically ill patients with life-threatening compromises in cardiac and/or
      respiratory function. The unpredictability of ECMO resources for a large
      pediatric and adult population prompted a need for the ability to respond to
      significant fluctuations in the volume of patients on ECMO. Through
      multidisciplinary collaboration, the Primary Care Giver (PCG) ECMO Staffing Model
      was developed to accommodate unpredictable fluctuations in ECMO activity and to
      maintain flexibility and fiscal responsibility in turbulent economic times.
      Advancements in extracorporeal technology supported the opportunity to develop a
      safe and extended staffing model for ECMO. Combining the use of a centrifugal
      pump system with specialized and experienced cardiovascular intensive care nurses
      and the ECMO specialist team provided a milieu for education and training to
      support the new staffing model. The PCG ECMO model provides a safe, flexible, and
      fiscally responsible staffing model for variable ECMO activity.

PMID- 22157492
TI  - Evidence-based thermoregulation for adult trauma patients.
AB  - The purpose of this project was to develop a staff nurse-led initiative to
      implement and evaluate evidence-based thermoregulation care for adult trauma
      patients. An evidence-based practice protocol was developed and implemented,
      addressing varying patient needs across the spectrum of hypothermia seen in
      practice, serving as a guide for improving thermoregulation care in trauma
      patients. There were 2 key pieces to the evidence-based practice protocol. The
      first piece consisted of an interdisciplinary thermoregulation flowchart to
      provide focused care based on patient temperatures. The flowchart outlined
      progressive interventions for increasing hypothermia. The second piece outlined
      the nursing assistant role, preparing the care area before patient arrival and
      assisting nursing staff during trauma care. Data from staff questionnaires and
      patient documentation were used in a pre- and postevaluation of the practice
      change. Improvements were demonstrated in staff feeling better prepared to
      identify patients with hypothermia, treat hypothermia, and document thermal care
      of trauma patients. Clinically important improvement in temperature control
      during emergency treatment in both moderate and severe hypothermic patients were
      observed. Ongoing monitoring is underway to promote integration of the practice
      change.

PMID- 22157493
TI  - Prone positioning: is it safe and effective?
AB  - Prone positioning has been used as a treatment option for patients with acute
      lung injury or acute respiratory distress syndrome (ARDS) since the early 1970s.
      Prone position and extended prone position ventilation have been shown to
      increase end-expiratory lung volume, alveolar recruitment, and oxygenation in
      patients with severe hypoxemic and acute respiratory failure. Prone positioning
      is not a benign procedure, and there are potential risks (complications) that can
      occur to both the patient and the health care worker. Notable complications that
      can arise include: unplanned extubation, lines pulled, tubes kinked, and back and
      other injuries to personnel. Prone positioning is a viable, inexpensive therapy
      for the treatment of severe ARDS. This maneuver consistently improves systemic
      oxygenation in 70% to 80% of patients with ARDS. With the utilization of a
      standardized protocol and a trained and dedicated critical care staff, prone
      positioning can be performed safely.

PMID- 22157494
TI  - Sternal wound care to prevent infections in adult cardiac surgery patients.
AB  - Sternal wound infection post-cardiac surgery is a serious complication that can
      lead to increased length of stay, substantial financial impact, and increased
      mortality. The occurrence of sternal wound infections has been reported from 0.4%
      to 4% of postoperative cardiac surgeries. It is imperative that every heart
      surgery program implements the best practice to prevent the detrimental effects
      of sternal wound infections. In an effort to improve the cardiothoracic (CT)
      surgery program in a community hospital, a decision was made to create a
      specialty floor including specialized nurses to care for open-heart surgery
      patients. In October 2010, a group of these nurses formed a working committee to
      explore ways to improve the overall care of our CT surgery patients. A vision and
      purpose for this committee were identified: (1) update and improve practice for
      CT surgery patients utilizing evidence-based standards, (2) successfully
      disseminate this information to all staff caring for the CT surgery patients, and
      (3) evaluate the impact of any practice changes on patient outcomes. An initial
      focus for the committee was to standardize sternal wound care among all staff
      members on the cardiovascular floors, cardiac care unit, and progressive care
      unit.

PMID- 22157495
TI  - Reliability of pressure ulcer staging: a review of literature and 1 institution's
      strategy.
AB  - Pressure ulcers are an increasing health care problem. Accurate identification
      and classification of pressure ulcers impacts patient outcomes, health care
      costs, and quality initiatives.To identify existing evidence related to answering
      the question "Does bedside nursing staff accurately and reliably stage pressure
      ulcers as evidenced in their documentation?" Further evidence from one large
      tertiary care center with pressure ulcer identification and staging by nurses is
      also reported. Cumulative Index to Nursing and Allied Health Literature and
      MEDLINE databases were searched to identify existing evidence on the accuracy and
      reliability of pressure ulcer classification by nurses. Two reviewers
      independently screened results. A total of 54 full-text articles were obtained
      for review and 10 were included for final review. In addition, the accuracy and
      consistency of pressure ulcer identification and staging were examined at one
      large tertiary health system by extracting data from electronic health records
      for 1488 patient visits and assessments for 1499 patients. Comparisons were done
      for pressure ulcer documentation from 1 nurse's assessment to the following shift
      nurse's assessment and from the bedside nurse's assessment to assessments done by
      pressure ulcer experts.Review of the literature revealed that the reliability of
      pressure ulcer identification and classification is limited and highly variable.
      Some reports in the literature suggested nurses had difficulty distinguishing a
      pressure ulcer from other types of wounds. In addition, inaccuracies in pressure
      ulcer documentation were also identified. Further analysis of data within one
      large tertiary health care system revealed unreliable pressure ulcer
      documentation.

PMID- 22157496
TI  - Reducing hazardous chemical exposures in the neonatal intensive care unit: a new
      role for nurses.
AB  - A wide range of toxic chemicals have been found in the umbilical cord blood of
      newborns, indicating the potential for health risks from chemical exposure that
      begin in utero. The neonatal intensive care unit (NICU) setting may also have
      potential chemical exposures that create health risks. Given the extreme
      vulnerability of this patient population, it is critical to minimize unnecessary
      hazardous chemicals. Neonatal intensive care unit nurses have an important role
      to play in making the NICU as safe as possible for their patients and themselves.
      This article will focus on the human health effects of several chemical exposures
      commonly found in the NICU for which nurses can help to eliminate or select safer
      alternatives: (1) diethylhexyl phthalates (a plasticizer commonly found in
      intravenous tubing/bags and other products); (2) bisphenol A (commonly found in
      the lining of baby formula cans); (3) personal care products used in the NICU;
      (4) cleaning, sterilants, and disinfectants; and (5) mercury. A tool for
      assessing environmental health risks will be presented and associated
      intervention options including purchasing policies; hospital-wide chemical
      policies; and development of institutional infrastructures, such as Green Teams,
      to address NICU and hospital-wide environmental health concerns. Nursing's
      evolving role in environmental health will be reviewed.

PMID- 22157497
TI  - A visit to the intensive cares unit: a family-centered culture change to
      facilitate pediatric visitation in an adult intensive care unit.
AB  - To guide family adjustment, an effort was made to facilitate pediatric visitation
      in an adult intensive care unit (ICU). Goals were to improve customer
      satisfaction and to raise staff comfort level with child visitation. After
      implementing an open visitation policy, concerns around pediatric visitation in
      the ICU remained. Fears centered on risks to both patient and child. Literature
      was reviewed before a book was written entitled A Visit to the ICU. It contained
      information about what a child visiting the ICU would see, hear, and feel when
      visiting a loved one. The book provided reassurance for caregivers and children,
      informing them about what to expect when visiting. The goal of the book was to
      provide caregivers with a framework for age-appropriate education. Staff
      education was provided on developmental stages, including a child's
      understandings of illness and death. Nursing interventions were reviewed and
      resources provided. A survey demonstrated that the book increased staff comfort
      level with children visiting the unit, was a positive tool for patients and
      families, and eased fears among children while helping to facilitate coping
      mechanisms. The article will describe the practice change of pediatric visitation
      in an ICU and how it could be applied to other critical care settings.

PMID- 22157498
TI  - Hyperuricemia, gout and the kidney.
AB  - PURPOSE OF REVIEW: (a) To examine the latest information about renal tubular
      handling of uric acid, its genetic background and contribution to the causation
      of hyperuricemia. (b) To review the association of hyperuricemia, gout and
      chronic kidney damage and whether hyperuricemia is cause or effect of renal
      dysfunction. RECENT FINDINGS: The gene SLC2A9 encodes for GLUT9, an important
      proximal tubule transporter of uric acid. Polymorphisms of the gene have been
      linked to gout susceptibility and to hereditary hypouricemia. Familial childhood
      gout with progressive renal impairment attributable to mutations of the
      uromodulin (UMOD) gene is associated with reduced uromodulin in the proximal
      tubule cilia. Familial juvenile hyperuricemic nephropathy (FJHN) is one of three
      similar clinical disorders associated with uromodulin gene mutations. Genetic
      studies of urate transportation and of uromodulin-related nephropathy emphasize
      the pivotal importance of the proximal tubule in uric acid homeostasis. Studies
      of allopurinol and febuxostat lowering of serum urate have once again raised the
      tantalizing possibility that hyperuricemia is harmful to the kidneys by showing
      better preservation of glomerular filtration rate (GFR) in treated patients.
      SUMMARY: Renal tubular handling of uric acid is dependent on tubular
      transporters, one of which is GLUT9. Mutations of its gene SLC2A9 are associated
      with aberrations of uric acid disposal. Familial hyperuricemia due to uromodulin
      deficiency precedes but does not cause kidney failure. Nevertheless, both
      allopurinol and febuxostat treatment has sustained the hypothesis that
      hyperuricemia itself can have an adverse impact on kidney function.

PMID- 22157500
TI  - Ultrasonographic evaluation of the peripheral nerves in a patient with chronic
      neuropathy and dandy-walker syndrome.

PMID- 22157501
TI  - History of rehabilitation in Latin America.
AB  - Rehabilitation in Latin America was pioneered in the 1940s by orthopedists who
      envisioned the need for the integration of people with disabilities into society.
      The objective of this review is to discuss the evolution of rehabilitation in
      Latin America during the last few decades. This review is divided into the
      following sections: (1) prehistory, (2) the beginning, (3) common features in
      different countries, (4) the beginning and consolidation of the specialty, (5)
      the Latin American Medical Association of Rehabilitation, and (6) journals
      published by different countries.

PMID- 22157502
TI  - Ultrasound-guided intra-articular knee injection in an obese patient.
AB  - A 35-yr-old woman was referred to our outpatient clinic for a right intra
      articular knee aspiration and injection. She had a medical history notable for
      lymphedema and morbid obesity (Fig. 1). Her body mass index was recently
      calculated at greater than 60 kg/m(2). She had a history of four previous
      nonguided knee joint injections performed elsewhere that provided no significant
      improvement in pain. On physical examination, it was difficult to localize common
      knee joint bony landmarks, including the medial and lateral borders of the
      patella (Fig. 2). Consequently we opted to utilize ultrasound guidance for the
      knee joint injection via the technique described herein.

PMID- 22157503
TI  - Happiness and longevity.

PMID- 22157504
TI  - The role of healing modalities (complementary/alternative medicine) in holistic
      nursing practice.

PMID- 22157505
TI  - Healing: through the lens of intentionality.
AB  - Understanding and studying healing is one of our challenges as health care
      providers. This study is a presentation of a secondary analysis of data collected
      to study intentionality in the context of healing. Six healers and 6 healees,
      five of each who participate as dyads, described their experiences and their
      concepts of healing. The theory, Intentionality: the Matrix for Healing (IMH), is
      presented along with a more expanded definition of healing as an awareness of
      shift and a transformative process.

PMID- 22157506
TI  - The journey of women with breast cancer who engage in mindfulness-based stress
      reduction: a qualitative exploration.
AB  - This phenomenological study explores the "lived experience" of 8 women with stage
      I or II breast cancer who used mindfulness-based stress reduction (MBSR). The
      following 4 themes were identified: (1) the cancer journey: a shift in
      perception, (2) the treatment journey: the experience of MBSR, (3) the journey
      toward recovery, and (4) the journey toward self.

PMID- 22157507
TI  - Dietary issues inpatients face with being vegetarian: an integrative review.
AB  - This article reviews the literature from 1985 through 2010 on research related to
      the dietary issues vegetarian inpatients may encounter in the acute care setting.
      A thematic portrayal of vegetarianism in the context of the inpatient setting is
      described. Implications for future research and nursing practice are identified.

PMID- 22157508
TI  - Herbal remedies, mood, and cognition.
AB  - Herbal medicines were the "sole" source of medicine for thousands of years, in
      every culture since the advent of human civilization. Today, patients are
      increasing the use of these botanicals for numerous conditions, such as mood and
      cognition. This article will explore commonly used herbal remedies for mood and
      cognition functioning. It is imperative that nurses and nurse practitioners
      obtain expertise with these botanicals with regard to efficacy, adverse effects
      and contraindications, possible drug interactions, and safety considerations.

PMID- 22157509
TI  - Investigation of the anxiolytic effects of naringenin, a component of Mentha
      aquatica, in the male Sprague-Dawley rat.
AB  - This was a prospective, randomized, between-subjects experimental study to
      investigate the anxiolytic effects of naringenin, a component of mentha aquatica,
      and its potential interaction with the benzodiazepine binding site on the gamma
      aminobutyric acid (GABAA) receptor in the rat. Fifty-five rats were assigned to
      one of 5 groups with 11 rats per group: control, naringenin, midazolam, midazolam
      with naringenin, and flumazenil with naringenin. The elevated plus maze measured
      the behavioral components of anxiety and motor movements. Our data suggest that
      naringenin does not produce anxiolysis by modulation of the GABAA receptor;
      however, the findings indicate that naringenin decreases motor movements (P <
      .05).

PMID- 22157510
TI  - Menopause: a standardized isopropanolic black cohosh extract (remifemin) is found
      to be safe and effective for menopausal symptoms.
AB  - This randomized, double-blind, placebo-controlled, multicenter clinical study
      investigated the efficacy and various safety aspects of a standardized
      proprietary isopropanolic extract of black cohosh (Remifemin) in a population of
      304 postmenopausal women who met strict parameter guidelines that determined the
      inclusion criteria. This clinical study confirmed previous results, which clearly
      indicate the efficacy and tolerability of this proprietary black cohosh extract
      (Remifemin) in addressing menopausal symptoms, particularly hot flashes.

PMID- 22157511
TI  - Small intestine gastrointestinal stromal tumors.
AB  - PURPOSE OF REVIEW: To review the contemporary management of gastrointestinal
      stromal tumor (GIST), including endoscopy, surgery, and systemic therapy,
      highlighting the aspects unique to small intestinal tumors. RECENT FINDINGS:
      Tumor size, mitotic count, and site of origin are the three key prognostic
      factors, with mitotic count being the single strongest predictor of recurrence.
      Tumors arising in the small bowel have worse prognosis than those of comparable
      size and mitotic count arising in other organs. Endoscopy and endoscopic
      ultrasound-guided, fine-needle aspiration are key components in the diagnosis of
      GIST. The role of endoscopy in surveillance and resection remain investigational.
      Surgery, either open or laparoscopic, remains the only curative option, but
      recurrence rates are high. Adjuvant therapy with imatinib mesylate improves
      recurrence-free survival rates and may improve overall survival (OS) with longer
      duration of treatment. Neoadjuvant imatinib may play an important role in the
      management of patients with locally advanced disease. For patients with advanced
      disease, first-line imatinib and second-line sunitinib malate have improved
      progression-free and OS rates. Systemic treatment should be continued life-long
      or until treatment failure. SUMMARY: Advances in the last decade have
      dramatically changed the management and prognosis of patients with primary and
      advanced GIST.

PMID- 22157512
TI  - Small intestinal ion transport.
AB  - PURPOSE OF REVIEW: In this review, we focus on the recent (March 2010 to
      September 2011) advances in small intestinal ion transport, with particular
      emphasis on sodium, chloride, bicarbonate, and calcium transport mechanisms under
      physiological and pathophysiological conditions. RECENT FINDINGS: Knockout of
      NHERF1 and NHERF2 allowed translation of the data largely derived from the in
      vitro models into a living organism. These studies also expand our knowledge
      about the complexity of intestinal transporter interactomes, define the role for
      scaffolding proteins in basal and regulated apical transport, and help identify
      potential targets for pharmacological approaches. We continue to accumulate novel
      information about the function and regulation of NHE3 (including its role in
      regulating paracellular Ca2+ flux), NHE8, as well as about the complexity of the
      intestinal Cl- and HCO3- transport in health and disease. SUMMARY: Thanks to the
      new genetically engineered mouse models, a significant progress has been made in
      our understanding of the role of NHERF proteins in regulation of intestinal Na+
      absorption. Significant novel data on the coordinated function of bicarbonate,
      chloride, and sodium transporters contributes to our current views of the
      integrative physiology of the small intestinal electrolyte transport.

PMID- 22157513
TI  - Survivors of ventricular fibrillation have persistent cardiovascular risk factors
      late in follow-up.
AB  - OBJECTIVE: Implantable cardioverter-defibrillators (ICDs) prevent arrhythmic
      death, but do not modify disease progression. The prevalence of persistent
      cardiovascular risk factors in patients receiving an ICD and their adherence to
      optimal pharmacological therapy at late follow-up is unknown. The aim of this
      study was to assess the prevalence of cardiovascular and specific sudden cardiac
      arrest (SCA) risk factors, and the pharmacological treatment in ICD recipients
      who survived SCA caused by ventricular fibrillation (VF). DESIGN: Cross-sectional
      study. A total of 100 consecutive ICD patients who survived SCA due to documented
      VF, not due to a transient or reversible cause or an arrhythmogenic disease, were
      interviewed and examined at the routine outpatient clinic. RESULTS: The mean age
      of the patients was 60 +/- 11 years, and they were analysed at a median interval
      of 1092 days after SCA. The majority of patients had coronary artery disease. The
      New York Heart Association class at the time of implantation was >= II in 62%. A
      single chamber device was used in 49% and a resynchronization device in 12%. At
      the routine control, the most prevalent risk factors were overweight or obesity
      (63%), hypertension (41%), and smoking (16%). Pharmacological therapy was
      suboptimal in 18-32% of the patients. Eight per cent of the patients had known
      diabetes and 29% had elevated HbA1c levels. While only 7% had pre-existing overt
      heart failure, 43% had N-terminal pro-brain natriuretic peptide levels >= 100
      pmol/l. High sensitivity C-reactive protein was >= 3 mg/l in 52% of the patients.
      Family history was positive for sudden cardiac death (SCD) in 46% of the
      patients. CONCLUSIONS: Despite regular medical consultation, a large proportion
      of the patients had persistent cardiovascular risk factors and were often
      suboptimally treated. Unexpectedly, latent heart failure and unrecognized
      diabetes are observed in a large proportion of the patients, as well as elevated
      inflammatory markers. Genetic analysis may be rewarding, as 46% of the patients
      had a family history of SCD. Full medical attention, optimizing drug therapy, and
      counselling of these patients is necessary.

PMID- 22157514
TI  - Impact of bilateral open and closed-angle glaucoma on glaucoma-specific
      functioning in Asians.
AB  - PURPOSE: To evaluate the impact of bilateral primary glaucoma on glaucoma
      specific functioning in Asians. METHODS: Patients with bilateral primary open
      angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) aged 40 years or
      above of Chinese ethnicity in Singapore were recruited. All underwent a
      comprehensive clinical assessment of glaucoma. Glaucoma was diagnosed with a
      standard criteria including optic disc abnormality and visual field defect. The
      Glaucoma Quality of Life-15, a glaucoma-specific questionnaire, was used to
      evaluate the impact of glaucoma, and Rasch analysis was used to validate the
      Glaucoma Quality of Life-15. RESULTS: A total of 192 patients (mean+/-SD age,
      65.73+/-17.6 y and 65.1% male) were recruited, of which 56.2% (n=108) and 43.8%
      (n=84) had POAG and PACG, respectively. Fifty-four (28.1%), 85 (44.3%), and 53
      (27.6%) had bilateral mild glaucoma, mild glaucoma in 1 eye and moderate/severe
      glaucoma in the other, and bilateral moderate/severe glaucoma, respectively. In
      multivariate analyses, compared with patients with mild glaucoma in both eyes,
      those with (a) mild glaucoma in 1 eye and moderate/severe in other; and (b)
      moderate/severe glaucoma in both eyes, reported significantly poorer functioning
      (beta-coefficient=-8.20; confidence interval, -14.36 to -2.04; P<0.05) and (beta=
      21.05; confidence interval, -28.06 to -14.04; P<0.05), respectively. A similar
      independent association was found for POAG and PACG. These associations were also
      considered to be clinically significant while comparing bilateral mild glaucoma
      with bilateral moderate/severe glaucoma. We however, found no significant
      difference for functioning and severity of glaucoma between PACG and POAG
      patients (P<0.05). CONCLUSIONS: Bilateral glaucoma is worse than the mild form in
      any eye and is significantly associated with poor glaucoma-specific functioning
      in this Singaporean Chinese sample. These data emphasize the need for strategies
      to identify patients early and prevent deterioration beyond the mild form of the
      condition.

PMID- 22157515
TI  - Canaloplasty with intraoperative low dosage mitomycin C:  a retrospective case
      series.
AB  - PURPOSE: To evaluate the safety and preliminary efficacy of intraoperative
      mitomycin C (MMC) in conjunction with canaloplasty for the treatment of open
      angle glaucoma. METHODS: Observational case series. A microcatheter was used to
      viscodilate the full circumference of Schlemm canal and to place a trabecular
      meshwork tensioning suture. Low dosage MMC was applied beneath the superficial
      scleral flap before dissecting the second, deep scleral flap and accessing
      Schlemm canal. Qualifying preoperative intraocular pressures (IOPs) were at least
      16 mm Hg with a historical maximum IOP of at least 21 mm Hg. Primary outcome
      measures including visual acuity and adverse events are reported for a 12-month
      postoperative period. Secondary outcome measures included IOP and glaucoma
      medication usage. RESULTS: In 20 eyes of 20 consecutive patients, adverse events
      were generally transient and not sight threatening. With the use of MMC, there
      was an increased rate of hypotony as compared with reported results of prior
      canaloplasty studies. The mean logMAR best corrected visual acuity at baseline
      was 0.07 +/- 0.12 with a mean of 0.09 +/- 0.13 at 12 months (P=0.679). Mean IOP
      decreased from a preoperative value of 23.4 +/- 4.3 mm Hg on 2.2 +/- 1.2
      antiglaucoma medications to 13.4 +/- 4.3 mm Hg on no medications at 12 months. At
      all intervals, IOP and medication use results were significantly reduced versus
      baseline (P<0.001). CONCLUSIONS: The adjunctive use of MMC in canaloplasty is
      safe and effective.

PMID- 22157516
TI  - [Renal physiology].
AB  - The kidneys are responsible for the urinary excretion of uremic toxins and the
      regulation of several body systems such as intra and extracellular volume status,
      acid-base status, calcium and phosphate metabolism or erythropoiesis. They adapt
      quantitative and qualitative composition of the urine to keep these systems in
      balance. The flow of plasma is filtered in the range of 120 mL/min, and depends
      on the systemic and renal hemodynamics which is subject to self-regulation. The
      original urine will then be modified in successive segments of the nephron. The
      proximal nephron is to lead the massive reabsorption of water and essential
      elements such as sodium, bicarbonates, amino-acids and glucose. The distal
      nephron includes the distal convoluted tubule, the connector tube and the
      collecting duct. Its role is to adapt the quality composition of urine to the
      needs of the body.

PMID- 22157517
TI  - The role of the self in physical health: testing the effect of a values
      affirmation intervention on weight loss.

PMID- 22157518
TI  - Time discounting predicts creditworthiness.

PMID- 22157519
TI  - Angiotensin II-antagonist in paroxysmal atrial fibrillation (ANTIPAF) trial.
AB  - BACKGROUND: Unlike antiarrhythmic drugs, the safety and beneficial effects of
      angiotensin II receptor blockade (ARB) in patients with structural heart disease
      is well established. The clinical efficacy of ARBs to prevent atrial fibrillation
      (AF) so far only has been shown in patients with structural heart disease. Here,
      we report the primary outcome of the Angiotensin II-Antagonist in Paroxysmal
      Atrial Fibrillation (ANTIPAF) trial, which investigated the effect of olmesartan
      medoxomil compared with placebo on AF burden in patients with paroxysmal AF
      without structural heart disease. METHODS AND RESULTS: The ANTIPAF trial was a
      prospective, randomized, placebo-controlled, multicenter trial analyzing the AF
      burden (percentage of days with documented episodes of paroxysmal AF) during a 12
      month follow-up as the primary study end point. Four hundred thirty patients with
      documented paroxysmal AF without structural heart disease were randomized to
      placebo or 40 mg olmesartan per day. Concomitant therapy with ARBs, angiotensin
      converting enzyme inhibitors, and antiarrhythmic drugs was prohibited. Patients
      were followed using daily transtelephonic ECG (tele-ECG) recordings independent
      of symptoms. The intention-to-treat population of the trial encompassed 425
      patients (placebo group, n=211; olmesartan group, n=214). A total of 87 818 tele
      ECGs were analyzed in these patients during follow-up (placebo group, 44 888
      ECGs; olmesartan group, 42 930 ECGs). Thus, a mean of 207 tele-ECGs were recorded
      per patient. The primary end point (AF burden) was not different between the 2
      groups (P=0.770). Secondary outcome parameters, including quality of life, also
      were not different. In particular, time to first AF recurrence, time to
      persistent AF, and number of hospitalizations were not different between the 2
      groups. The time to prescription of recovery medication (amiodarone) was the only
      parameter showing an intergroup difference, with earlier prescription of
      amiodarone in the placebo group (P=0.022). CONCLUSIONS: One year of ARB therapy
      per se does not reduce the number of AF episodes in patients with documented
      paroxysmal AF without structural heart disease. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00098137.

PMID- 22157520
TI  - Atrial fibrillation after pulmonary transplantation: incidence, impact on
      mortality, treatment effectiveness, and risk factors.
AB  - BACKGROUND: Atrial fibrillation (AF) is common after thoracic surgery. Limited
      data exist concerning the incidence of AF, its impact on mortality, the
      effectiveness of therapy, and the risk factors of AF after pulmonary
      transplantation. METHODS AND RESULTS: We reviewed the medical files of 224
      consecutive lung transplant recipients who underwent surgery over a 10-year
      period at a large Canadian center. We collected patient characteristics, in
      hospital treatments, and outcomes. Time-to-event analysis was used to account for
      in-hospital follow-up and models generated to assess the impact of AF on
      mortality and independent risk factors of AF after transplantation. Postoperative
      AF occurred in 65 patients (29%). AF was more likely to occur with complications
      such as pneumonia, mediastinitis, and bronchial dehiscence and was not an
      independent risk factor of mortality (hazard ratio=1.56; 95% confidence interval,
      0.52-4.63). Pharmacological or electric therapy for rhythm or rate control of AF
      was administered to 97% of patients. Intravenous amiodarone was used in 46%,
      electric cardioversion in 28%, and heparin in 26%. Only 1 patient remained in AF
      at discharge. Age (hazard ratio=1.08 by year; 95% confidence interval, 1.05
      1.12), bilateral transplantation (hazard ratio=1.87; 95% confidence interval,
      1.03-3.42), and a history of AF before the transplantation (hazard ratio=4.48;
      95% confidence interval, 1.05-19.11) were found to be independently associated
      with an increased incidence of postoperative AF. CONCLUSIONS: AF is fairly common
      after pulmonary transplantation, transient, and relatively benign. It is not
      independently associated with increased in-hospital mortality. Most patients
      return to sinus rhythm before discharge. Age, prior AF, and bilateral
      transplantation increase the risk of postoperative AF.

PMID- 22157521
TI  - Crescendo in depolarization and repolarization heterogeneity heralds development
      of ventricular tachycardia in hospitalized patients with decompensated heart
      failure.
AB  - BACKGROUND: A critical need exists for reliable warning markers of in-hospital
      life-threatening arrhythmias. We used a new quantitative method to track
      interlead heterogeneity of depolarization and repolarization to detect
      premonitory changes before ventricular tachycardia (VT) in hospitalized patients
      with acute decompensated heart failure. METHODS AND RESULTS: Ambulatory ECGs
      (leads V(1), V(5), and aVF) recorded before initiation of drug therapy from
      patients enrolled in the PRECEDENT (Prospective Randomized Evaluation of Cardiac
      Ectopy with Dobutamine or Nesiritide Therapy) trial were analyzed. R-wave
      heterogeneity (RWH) and T-wave heterogeneity (TWH) were assessed by second
      central moment analysis and T-wave alternans (TWA) by modified moving average
      analysis. Of 44 patients studied, 22 had experienced episodes of VT (>=4 beats at
      heart rates >100 beats/min) following >=120 minutes of stable sinus rhythm, and
      22 were age- and sex-matched patients without VT. TWA increased from 18.6+/-2.1
      MUV (baseline, mean+/-SEM) to 27.9+/-4.6 MUV in lead V(5) at 15 to 30 minutes
      before VT (P<0.05) and remained elevated until the arrhythmia occurred. TWA
      results in leads V(1) and aVF were similar. RWH and TWH were elevated from
      164.1+/-33.1 and 134.5+/-20.6 MUV (baseline) to 299.8+/-54.5 and 239.2+/-37.0 MUV
      at 30 to 45 minutes before VT (P<0.05), respectively, preceding the crescendo in
      TWA by 15 minutes. Matched patients without VT did not display elevated RWH
      (185.5+/-29.4 MUV) or TWH (157.1+/-27.2 MUV) during the 24-hour period.
      CONCLUSIONS: This investigation is the first clinical demonstration of the
      potential utility of tracking depolarization and repolarization heterogeneity to
      detect crescendos in electrical instability that could forewarn of impending
      nonsustained VT. Clinical Trial Registration- URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00270400.

PMID- 22157522
TI  - Investigating the role of the coronary vasculature in the mechanisms of
      defibrillation.
AB  - BACKGROUND: The direct role of coronary vessels in defibrillation, although
      hypothesized to be important, remains to be elucidated. We investigated how
      vessel-induced virtual electrode polarizations assist reentry termination.
      METHODS AND RESULTS: A highly anatomically detailed rabbit ventricular slice
      bidomain computer model was constructed from 25-MUm magnetic resonance data,
      faithfully representing both structural and electric properties of blood vessels.
      For comparison, an equivalent simplified model with intramural cavities filled in
      was also built. Following fibrillation induction, 6 initial states were selected,
      and biphasic shocks (5-70 V) were applied using a realistic implanted
      cardioverter-defibrillator electrode configuration. A fundamental mechanism of
      biphasic defibrillation was uncovered in both models, involving successive break
      excitations (after each shock phase) emanating from opposing myocardial surfaces
      (in septum and left ventricle), which rapidly closed down excitable gaps. The
      presence of vessels accelerated this process, achieving more-rapid and successful
      defibrillation. Defibrillation failed in 5 cases (all because of initiation of
      new activity) compared with 8 with the simplified model (5/8 failures because of
      surviving activity). At stronger shocks, virtual electrodes formed around
      vessels, rapidly activating intramural tissue because of break excitations,
      assisting the main defibrillation mechanism, and eliminating all activity <15 ms
      of shock end in 60% of successful shocks (36% in simplified model). Subsequent
      analysis identified that only vessels >200 MUm in diameter participated through
      this mechanism. Consequently, wavefronts could survive intramurally in the
      simplified model, leading to reentry and shock failure. CONCLUSIONS: We provide
      new insight into defibrillation mechanisms by showing how intramural blood
      vessels facilitate more-effective elimination of existing wavefronts, rapid
      closing down of excitable gaps, and successful defibrillation and give guidance
      toward the required resolution of cardiac imaging and model generation endeavors
      for mechanistic defibrillation analysis.

PMID- 22157523
TI  - Descemet stripping automated endothelial keratoplasty using infant donor tissue.
AB  - PURPOSE: The purpose of this study was to report the outcomes of Descemet
      stripping automated endothelial keratoplasty (DSAEK) surgery using infant (2
      years and younger) donor tissue. METHODS: Retrospective interventional case
      series of 3 patients. RESULTS: All 3 patients in this series had good visual
      outcomes and clear DSAEK grafts. The average endothelial cell count (ECC) from
      infant donors was very high (4239 cells/mm(2)). Similarly, the average
      postoperative ECC was also high (3359 cells/mm(2)) with a mean endothelial cell
      loss of 20.9% at 11-month follow-up. One patient remarkably had an ECC of 4065
      cells per square millimeter at 1-year follow-up with a net endothelial cell loss
      of only 13.3%. No difficulties were noted using infant donor tissue, including
      the intraoperative use of the Moria microkeratome to prepare the DSAEK donor,
      insertion of the donor graft, or with air-bubble management. CONCLUSIONS: Using
      infant donor tissue for DSAEK surgery is safe and may be preferable, particularly
      for younger patients. The higher preoperative endothelial cell densities in
      infant donor tissue should improve graft survival and long-term maintenance of
      corneal transparency provided that surgery-related endothelial cell loss is
      minimized.

PMID- 22157524
TI  - Pure and simple:  work-life balance.

PMID- 22157525
TI  - Society of trauma nurses: explore the opportunities.

PMID- 22157526
TI  - Electronic trauma patient outcomes assessment tool: performance improvement in
      the trauma intensive care unit.
AB  - An electronic dashboard can enhance compliance with a specific checklist of
      indicators with daily management of injured patients in a trauma intensive care
      unit effectively. A performance management electronic dashboard monitored 24
      indicators in the trauma intensive care unit over a 3-year period. Over a 3-year
      period, utilization of the electronic dashboard improved from 64% to 100% and
      mean compliance rose from 94.8% to 97.4%. Implementation of an electronic
      dashboard enhances compliance in managing trauma patients in a sustainable
      manner, allows immediate correction of deficiencies, monitors trends, and
      facilitates performance improvement/patient safety initiatives of a trauma
      program.

PMID- 22157528
TI  - Surrogate decision making for patients with severe traumatic brain injury.
AB  - Each year more than 1.7 million people experience traumatic brain injury. This
      qualitative descriptive study sought to describe how surrogate decision makers
      for patients with severe traumatic brain injury made the decision to withdraw or
      continue life support, and whether they believed that the health care team could
      have been of greater assistance. Six of 10 surrogates elected to withdraw life
      sustaining treatment. Eight surrogates said that they would make the same proxy
      decisions if they had to do it again. Surrogates used multiple inputs to make
      treatment decisions and described the need for support from a trauma advanced
      practice nurse or palliative care team.

PMID- 22157529
TI  - Trauma performance improvement and patient safety committee: fostering an
      effective team.
AB  - Trauma programs that are verified by the American College of Surgeons are
      required to have a multidisciplinary committee that examines trauma-related
      patient care operations. To facilitate a potentially large number of issues
      relevant to patient care, the Trauma Performance Improvement and Patient Safety
      Committee can apply team principles to promote success. A literature review
      concerning effective teams was conducted. Eleven principles were identified as
      essential for developing an effective committee that can properly respond to and
      resolve performance issues in complex trauma care. This article describes and
      applies these 11 principles to the Trauma Performance Improvement and Patient
      Safety Committee.

PMID- 22157530
TI  - Influence of moral distress on the professional practice environment during
      prognostic conflict in critical care.
AB  - Study purpose was to describe critical care nurses' levels of moral distress and
      the effects of that distress on their professional practice environment. A
      descriptive, correlational, prospective, survey design was used. The intensity of
      moral distress was inversely related to physician/nurse collegial relationships
      and the frequency of moral distress was inversely related to all aspects of the
      professional practice environment except foundations for quality of care. It is
      important to monitor the frequency of moral distress. Strategies to improve the
      nurse's sense of control over practice, teamwork, communication, and autonomy
      need to be developed and tested in future research.

PMID- 22157531
TI  - Trauma resuscitations and patient perceptions of care and comfort.
AB  - Patients subjected to common trauma resuscitation practices can have varied
      emotional responses to certain aspects of their initial evaluation and care.
      Thirty-four patients admitted to the hospital after blunt traumatic injury were
      randomly selected to complete a self-reported questionnaire regarding their
      comfort levels with certain aspects of their initial trauma care and
      resuscitation. Most patients reported higher levels of comfort with procedures
      generally expected by the lay public and lower levels of comfort with those
      procedures less well known or for which they were not prepared. Analysis of
      survey data showed a larger percentage of discomfort with the digital rectal
      examination than with other aspects of trauma care. Notably, data analysis also
      showed a significant percentage of patients who were reluctant to disclose
      receiving a digital rectal examination. Additional investigation into the
      validity and reproducibility of these trends is warranted; however, there is
      legitimate evidence that there is room to improve a patient's perception of
      comfort during a trauma resuscitation and initial workup through improved
      communication and procedure disclosure.

PMID- 22157533
TI  - Comparing rural ground and air emergency medical services: a level I trauma
      center's experience.
AB  - We sought to compare differences in patients transported by ground and air
      emergency medical services directly from the scenes of their injuries to a rural
      level I trauma facility. Variables examined included age, gender, vital signs,
      Glasgow Coma Scale score, discharge location, length of stay, and survival
      metrics. Student t tests and odds ratios were used for analysis. Demographics and
      vital signs differed between trauma patients transported by air versus those
      transported by ground. Generally, length of stay was longer in air-transported
      patients, who also had poorer survival metrics with negligible risk of death.
      Significant differences exist in the markers of physiology such as vital signs,
      expected survival, and degree of injury.

PMID- 22157534
TI  - Duodenal transection in child abuse.

PMID- 22157535
TI  - Comparison of visual acuity and automated perimetry findings in patients with
      neuromyelitis optica or multiple sclerosis after single or multiple attacks of
      optic neuritis.
AB  - OBJECTIVE: To review the clinical characteristics of patients with neuromyelitis
      optica (NMO) and to compare their visual outcome with those of patients with
      optic neuritis (ON) and multiple sclerosis (MS). METHODS: Thirty-three patients
      with NMO underwent neuro-ophthalmic evaluation, including automated perimetry
      along with 30 patients with MS. Visual function in both groups was compared
      overall and specifically for eyes after a single episode of ON. RESULTS: Visual
      function and average visual field (VF) mean deviation were significantly worse in
      eyes of patients with NMO. After a single episode of ON, the VF was normal in
      only 2 of 36 eyes of patients with NMO compared to 17 of 35 eyes with MS (P <
      0.001). The statistical analysis indicated that after a single episode of ON, the
      odds ratio for having NMO was 6.0 (confidence interval [CI]: 1.6-21.9) when VF
      mean deviation was worse than -20.0 dB while the odds ratio for having MS was
      16.0 (CI: 3.6-68.7) when better than -3.0 dB. CONCLUSION: Visual outcome was
      significantly worse in NMO than in MS. After a single episode of ON, suspicion of
      NMO should be raised in the presence of severe residual VF deficit with automated
      perimetry and lowered in the case of complete VF recovery.

PMID- 22157536
TI  - Relationship between NMO-antibody and anti-MOG antibody in optic neuritis.
AB  - BACKGROUND: Damage to astrocytes by anti-aquaporin-4 antibody (AQP4-Ab), also
      known as NMO antibody, has been implicated as the cause of neuromyelitis optica.
      Myelin oligodendrocyte glycoprotein (MOG) is well known as the causative protein
      of multiple sclerosis (MS). MOG antigen is currently considered as a cause of
      optic neuritis (ON) associated with MS because immunization with MOG antigen
      derived from oligodendrocytes induces murine ON with myelitis. We investigated
      the relationship between NMO antibody (NMO-Ab) and anti-MOG antibody (MOG-Ab) and
      potential in patients with ON for recovery of vision. METHODS: Thirty-three eyes
      of 23 patients with ON were studied. At presentation, serum NMO-Ab was measured
      by immunofluorescence using HEK 293 cells transfected with AQP4-GFP, and anti
      MOG1-125 antibody was measured by enzyme-linked immunosorbent assay. MOG-Ab
      seropositivity was defined by comparing with MOG-Ab level obtained from 8 healthy
      normal subjects. RESULTS: Eleven (47%) of 23 ON patients were NMO-Ab
      seropositive, while 8 (34%) of the 23 patients were MOG-Ab seropositive. Six
      (26%) of 23 patients were seropositive for both NMO-Ab and MOG-Ab. Ten (43%) of
      23 patients were seronegative for both antibodies. Three (50%) of 6 eyes of
      patients seropositive for both antibodies did not respond to corticosteroid pulse
      therapy and plasmapheresis, and visual acuity remained unchanged. In the NMO
      Ab/MOG-Ab group, visual acuity improved significantly (P < 0.0001). In the other
      3 groups (NMO-Ab/MOG-Ab, NMO-Ab/MOG-Ab, and NMO-Ab/MOG-Ab), visual acuity did not
      change significantly (P = 0.53, 0.42, and 0.45, respectively). CONCLUSION: NMO-Ab
      and MOG-Ab could be potential biomarkers to determine visual prognosis in
      patients with ON.

PMID- 22157537
TI  - Prediction of skeletal muscle and fat mass in patients with advanced cancer using
      a metabolomic approach.
AB  - Urine and plasma metabolites originate from endogenous metabolic pathways in
      different organs and exogenous sources (diet). Urine and plasma were obtained
      from advanced cancer patients and investigated to determine if variations in lean
      and fat mass, dietary intake, and energy metabolism relate to variation in
      metabolite profiles. Patients (n = 55) recorded their diets for 3 d and after an
      overnight fast they were evaluated by DXA and indirect calorimetry. Metabolites
      were measured by NMR and direct injection MS. Three algorithms were used [partial
      least squares discriminant-analysis, support vector machines (SVM), and least
      absolute shrinkage and selection operator] to relate patients' plasma/urine
      metabolic profile with their dietary/physiological assessments. Leave-one-out
      cross-validation and permutation testing were conducted to determine statistical
      validity. None of the algorithms, using 63 urine metabolites, could learn to
      predict variations in individual's resting energy expenditure, respiratory
      quotient, or their intake of total energy, fat, sugar, or carbohydrate. Urine
      metabolites predicted appendicular lean tissue (skeletal muscle) with excellent
      cross-validation accuracy (98% using SVM). Total lean tissue correlated highly
      with appendicular muscle (Pearson r = 0.98; P < 0.0001) and gave similar cross
      validation accuracies. Fat mass was effectively predicted using the 63 urine
      metabolites or the 143 plasma metabolites, exclusively. In conclusion, in this
      population, lean and fat mass variation could be effectively predicted using
      urinary metabolites, suggesting a potential role for metabolomics in body
      composition research. Furthermore, variation in lean and fat mass potentially
      confounds metabolomic studies attempting to characterize diet or disease
      conditions. Future studies should account or correct for such variation.

PMID- 22157539
TI  - The historical evolution of thought regarding multiple micronutrient nutrition.
AB  - Multiple micronutrient nutrition is an idea that originated in the 1940s and
      exemplifies the iterative nutritional paradigm. In the first four decades of the
      20th century, scientists sought to separate and characterize the vitamins that
      were responsible for xerophthalmia, rickets, pellagra, scurvy, and beriberi. The
      dietary requirements of the different micronutrients began to be established in
      the early 1940s. Surveys showed that multiple micronutrient deficiencies were
      widespread in industrialized countries, and the problem was addressed by use of
      cod-liver oil, iodized salt, fortified margarine, and flour fortification with
      multiple micronutrients, and, with rising living standards, the increased
      availability and consumption of animal source foods. After World War II, surveys
      showed that multiple micronutrient deficiencies were widespread in developing
      countries. Approaches to the elimination of multiple micronutrient deficiencies
      include periodic vitamin A supplementation, iodized salt, targeted iron/folate
      supplementation, fortified flour, other fortified foods, home fortification with
      micronutrient powders, and homestead food production. The prevention of multiple
      micronutrient malnutrition is a key factor in achieving the Millennium
      Development Goals, given the important effects of micronutrients on health and
      survival.

PMID- 22157538
TI  - Marginal biotin deficiency can be induced experimentally in humans using a cost
      effective outpatient design.
AB  - To date, marginal, asymptomatic biotin deficiency has been successfully induced
      experimentally by the use of labor-intensive inpatient designs requiring rigorous
      dietary control. We sought to determine if marginal biotin deficiency could be
      induced in humans in a less expensive outpatient design incorporating a self
      selected, mixed general diet. We sought to examine the efficacy of three
      outpatient study designs: two based on oral avidin dosing and one based on a diet
      high in undenatured egg white for a period of 28 d. In study design 1,
      participants (n = 4; 3 women) received avidin in capsules with a biotin binding
      capacity of 7 times the estimated dietary biotin intake of a typical self
      selected diet. In study design 2, participants (n = 2; 2 women) received double
      the amount of avidin capsules (14 times the estimated dietary biotin intake). In
      study design 3, participants (n = 5; 3 women) consumed egg-white beverages
      containing avidin with a biotin binding capacity of 7 times the estimated dietary
      biotin intake. Established indices of biotin status [lymphocyte propionyl-CoA
      carboxylase activity; urinary excretion of 3-hydroxyisovaleric acid, 3
      hydroxyisovaleryl carnitine (3HIA-carnitine), and biotin; and plasma
      concentration of 3HIA-carnitine] indicated that study designs 1 and 2 were not
      effective in inducing marginal biotin deficiency, but study design 3 was as
      effective as previous inpatient study designs that induced deficiency by egg
      white beverage. Marginal biotin deficiency can be induced experimentally by using
      a cost-effective outpatient design by avidin delivery in egg-white beverages.
      This design should be useful to the broader nutritional research community.

PMID- 22157540
TI  - Evidence for multiple micronutrient effects based on randomized controlled trials
      and meta-analyses in developing countries.
AB  - Providing multiple micronutrients via supplements, powders, or fortified ready-to
      use foods is increasingly becoming a strategy for simultaneously addressing
      multiple nutrient deficiencies in developing countries. The pros and cons of the
      "gold standard" randomized controlled trial (RCT) design and meta-analyses of
      trials for establishing efficacy of nutritional interventions are discussed. Over
      the past decade, numerous RCT have been undertaken to test the efficacy of
      multiple micronutrient supplementation in both pregnant women and young children.
      Outcomes of interest have ranged from birth weight to child growth, and infant
      morbidity and mortality to nutrient status and cognitive function. These RCT have
      also been submitted to meta-analyses for estimating pooled effect sizes for
      various outcomes. Meta-analyses of antenatal multiple micronutrient
      supplementation reveal a modest but significant increase in birth weight of 22.4
      g (95% CI: 8.3, 36.4 g) and an 11% (95% CI: 3, 19) reduction in low birth weight
      but no impact on preterm birth or perinatal mortality. In children, small effect
      sizes of 0.13 (95% CI: 0.06, 0.21) for length/height and 0.14 (95% CI: 0.03,
      0.25) for weight have been shown with 3 or more micronutrients compared to fewer
      micronutrients, but there is limited evidence for an impact on outcomes such as
      morbidity and cognitive function. Gaps in research and future challenges for
      programmatic application of this strategy for both pregnant women and young
      children are discussed.

PMID- 22157541
TI  - Correcting for inflammation changes estimates of iron deficiency among rural
      Kenyan preschool children.
AB  - The assessment of iron status where infections are common is complicated by the
      effects of inflammation on iron indicators and in this study we compared
      approaches that adjust for this influence. Blood was collected in 680 children
      (aged 6-35 mo) and indicators of iron status [(hemoglobin (Hb), zinc
      protoporphyrin (ZP), ferritin, transferrin receptor (TfR), and TfR/ferritin
      index)] and subclinical inflammation [(the acute phase proteins (APP) C-reactive
      protein (CRP), and alpha-1-acid glycoprotein (AGP)] were determined. Malaria
      parasitemia was assessed. Subclinical inflammation was defined as CRP >5 mg/L
      and/or AGP >1 g/L). Four groups were defined based on APP levels: reference
      (normal CRP and AGP), incubation (raised CRP and normal AGP), early convalescence
      (raised CRP and AGP), and late convalescence (normal CRP and raised AGP).
      Correction factors (CF) were estimated as the ratios of geometric means of iron
      indicators to the reference group of those for each inflammation group. Corrected
      values of iron indicators within inflammation groups were obtained by multiplying
      values by their respective group CF. CRP correlated with AGP (r = 0.65; P <
      0.001), ferritin (r = 0.38; P < 0.001), Hb (r = -0.27; P < 0.001), and ZP (r =
      0.16; P < 0.001); AGP was correlated with ferritin (r = 0.39; P < 0.001), Hb (r =
      -0.29; P < 0.001), and ZP (r = 0.24; P < 0.001). Use of CF to adjust for
      inflammation increased the prevalence of ID based on ferritin < 12 MUg/L by 34%
      (from 27 to 41%). Applying the CF strengthened the expected relationship between
      Hb and ferritin (r = 0.10; P = 0.013 vs. r = 0.20; P < 0.001, before and after
      adjustment, respectively). Although the use of CF to adjust for inflammation
      appears indicated, further work is needed to confirm that this approach improves
      the accuracy of assessment of ID.

PMID- 22157542
TI  - Kaempferol suppresses eosionphil infiltration and airway inflammation in airway
      epithelial cells and in mice with allergic asthma.
AB  - The airway epithelium is thought to play an important role in the pathogenesis of
      asthma. Airway epithelial activation may contribute to inflammatory and airway
      remodeling events characteristic of asthma. Kaempferol, a flavonoid with
      antioxidative and antitumor properties, has been studied as an antiinflammatory
      agent. However, little is known regarding its effects on allergic asthma. Human
      airway epithelial BEAS-2B cells and eosinophils were used to investigate the
      effects of kaempferol on endotoxin- or cytokine-associated airway inflammation.
      Kaempferol, nontoxic at 1-20 MUmol/L, suppressed LPS-induced eotaxin-1 protein
      expression that may be mediated, likely via Janus kinase 2 (JAK2) JAK2 signaling.
      Additionally, 1-20 MUmol/L kaempferol dose-dependently attenuated TNFalpha
      induced expression of epithelial intracellular cell adhesion molecule-1 and
      eosinophil integrin beta2, thus encumbering the eosinophil-airway epithelium
      interaction. Kaempferol blunted TNFalpha-induced airway inflammation by
      attenuating monocyte chemoattractant protein-1 transcription, possibly by
      disturbing NF-kappaB signaling. This study further investigated antiallergic
      activity of kaempferol in BALB/c mice sensitized with ovalbumin (OVA) and
      challenged with a single dose of OVA. Oral administration of kaempferol
      attenuated OVA challenge-elevated expression of eotaxin-1 and eosinophil major
      basic protein via the blockade of NF-kappaB transactivation, thereby blunting
      eosinophil accumulation in airway and lung tissue. Therefore, dietary kaempferol
      is effective in ameliorating allergic and inflammatory airway diseases through
      disturbing NF-kappaB signaling.

PMID- 22157544
TI  - Green tea extract suppresses NFkappaB activation and inflammatory responses in
      diet-induced obese rats with nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is characterized by oxidative stress and
      inflammatory responses that exacerbate liver injury. The objective of this study
      was to determine whether the antioxidant and antiinflammatory activities of green
      tea extract (GTE) would protect against NASH in a model of diet-induced obesity.
      Adult Wistar rats were fed a low-fat (LF) diet or high-fat (HF) diet containing
      no GTE or GTE at 1% or 2% (HF+2GTE) for 8 wk. The HF group had greater (P <=
      0.05) serum alanine (ALT) and aspartate aminotransferases and hepatic lipids than
      the LF group. Both GTE groups had lower ALT and hepatic lipid than the HF group.
      In liver and epididymal adipose, the HF group had lower glutathione as well as
      greater mRNA and protein expression of TNFalpha and monocyte chemoattractant
      protein-1 (MCP-1) and NFkappaB binding activity than the LF group. Compared to
      the HF group, the HF+2GTE group had greater glutathione and lower protein and
      mRNA levels of inflammatory cytokines in both tissues. NFkappaB binding
      activities at liver and adipose were also lower, likely by inhibiting the
      phosphorylation of inhibitor of NFkappaB. NFkappaB binding activities in liver
      and adipose (P <= 0.05; r = 0.62 and 0.46, respectively) were correlated with
      ALT, and hepatic NFkappaB binding activity was inversely related to liver
      glutathione (r = -0.35). These results suggest that GTE-mediated improvements in
      glutathione status are associated with the inhibition of hepatic and adipose
      inflammatory responses mediated by NFkappaB, thereby protecting against NASH.

PMID- 22157545
TI  - Current surgical outcomes for cranial base chordomas:  cohort study of 95
      patients.
AB  - BACKGROUND: Chordomas of the skull base are locally aggressive neoplasms for
      which maximal surgical resection confers prolonged survival. OBJECTIVE: To
      present the largest consecutive surgical series of cranial base chordomas to
      date, including complications, functional outcome, and overall (OS) and
      recurrence-free survival (RFS) in early and late eras of our experience. METHODS:
      From 1988 to 2011, 95 patients with cranial base chordomas were treated,
      including 56 patients from 1988 to 1999 and 39 from 2000 to 2011. Mean age and
      average follow-up were 42.6 +/- 16.8 years and 38.3 +/- 38.5 months,
      respectively. A historically controlled study design was implemented comparing
      both eras with respect to 5-year OS, RFS, Karnofsky performance scale at last
      follow-up, and complications. RESULTS: Mean 5-year OS and RFS for the entire
      cohort was 74% +/- 6% and 56% +/- 8%, respectively. Complete resection rates were
      similar between groups (68% and 74%, respectively; P = .494). In the 2000 to 2011
      era, overall (26%), cranial nerve (10%), vascular (3%), and systemic (0%)
      complications were less frequent than in the 1988 to 1999 era. Patients in the
      2000 to 2011 era were 1.50 times more likely to have a Karnofsky performance
      scale >= 70 than in the 1988 to 1999 era (95% confidence interval 1.15-1.94; P =
      .003). There was no significant difference in 5-year RFS between the 1988 to 1999
      and 2000 to 2011 eras. Five-year OS was higher in the 2000 to 2011 era (93% +/-
      6% vs 64% +/- 8% for the 1988-1999 era; P = .012). CONCLUSION: Aggressive
      surgical resection implementing contemporary skull base approaches can be
      performed with an acceptable complication profile with preservation of functional
      status, while conferring a similar OS and RFS.

PMID- 22157543
TI  - Stable nitrogen and carbon isotope ratios indicate traditional and market food
      intake in an indigenous circumpolar population.
AB  - The transition of a society from traditional to market-based diets (termed the
      nutrition transition) has been associated with profound changes in culture and
      health. We are developing biomarkers to track the nutrition transition in the
      Yup'ik Eskimo population of Southwest Alaska based on naturally occurring
      variations in the relative abundances of carbon and nitrogen stable isotopes
      (delta(15)N and delta(13)C values). Here, we provide three pieces of evidence
      toward the validation of these biomarkers. First, we analyzed the delta(15)N and
      delta(13)C values of a comprehensive sample of Yup'ik foods. We found that
      delta(15)N values were elevated in fish and marine mammals and that delta(13)C
      values were elevated in market foods containing corn or sugar cane carbon.
      Second, we evaluated the associations between RBC delta(15)N and delta(13)C
      values and self-reported measures of traditional and market food intake (n =
      230). RBC delta(15)N values were correlated with intake of fish and marine
      mammals (r = 0.52; P < 0.0001). RBC delta(13)C values were correlated with intake
      of market foods made from corn and sugar cane (r = 0.46; P < 0.0001) and total
      market food intake (r = 0.46; P < 0.0001). Finally, we assessed whether stable
      isotope ratios captured population-level patterns of traditional and market
      intake (n = 1003). Isotopic biomarkers of traditional and market intake were
      associated with age, community location, sex, and cultural identity. Self-report
      methods showed variations by age and cultural identity only. Thus, stable
      isotopes show potential as biomarkers for monitoring dietary change in indigenous
      circumpolar populations.

PMID- 22157546
TI  - Cranial plate anchoring of spinal cord stimulation paddle leads:  technical note.
AB  - BACKGROUND: Lead migration is a frequent complication of spinal cord stimulation
      (SCS) and requires revision surgery. The evolution of wider paddle leads has
      necessitated more extensive laminotomy and epidural adhesiolysis, which may
      increase the risk of lead migration. OBJECTIVE: We describe a novel anchoring
      technique for SCS paddle leads with use of a cranial "dogbone" plate. METHODS: We
      retrospectively reviewed a consecutive series of 11 patients who underwent
      placement of paddle lead spinal cord stimulators with titanium plate anchoring.
      Patients were followed for a mean of 29.5 months from SCS implantation (range, 5
      65 months). A 4-hole linear titanium cranial plate and two 4-mm screws were used
      to tightly affix the proximal paddle lead wiring to the lamina below the
      laminotomy defect. RESULTS: All patients continue to have satisfactory spinal
      cord stimulation with no loss of efficacy or need for revision. No complications
      have been attributed to titanium plate anchoring, and there have been no cases of
      lead migration with this technique. Titanium plate anchoring added minimal time
      (approximately 3-5 minutes) to the operative case. CONCLUSION: We report a safe
      and effective anchoring technique for paddle lead SCS with the use of a cranial
      plate. Our experience has been that this technique, which anchors the proximal
      lead wiring to the remaining lamina at the inferior laminotomy defect, is
      superior to anchoring methods that rely on suturing of lead wiring.

PMID- 22157547
TI  - Aneurysm embolization using detachable coils under intravascular ultrasonography
      guidance:  an in vitro feasibility study.
AB  - BACKGROUND: Intravascular ultrasonography (IVUS) has been used for guiding
      intravascular stent placement in interventional cardiology. OBJECTIVE: To
      evaluate the feasibility of aneurysm embolization by using detachable coils under
      IVUS guidance. METHODS: IVUS-guided embolization in conjunction with fluoroscopic
      imaging and subsequently alone were performed in a silicone model with a side
      wall aneurysm. IVUS-guided embolization in conjunction with fluoroscopic imaging
      was also used in an in vitro model of a side wall aneurysm created using sheep
      vessels. The visibility of the aneurysm, microcatheter, and coils ascertained by
      the IVUS was graded as excellent, good, or poor based on visualization of these
      items as distinct structures. The agreement between simultaneously acquired
      angiographic and IVUS images for detecting increasing intra-aneurysmal coil mass
      and coil prolapse was assessed in 10 and 6 simultaneously acquired angiographic
      and IVUS images, respectively. RESULTS: IVUS measurements of the aneurysm
      dimensions strongly correlated with standardized dimensions and measurements
      acquired by contrast angiography (Pearson coefficient of 0.96 and 0.99 for
      silicone model and arterial segment model, respectively). IVUS visualization of
      the aneurysm, microcatheter tip, and coil loops were graded as excellent in the
      silicone aneurysm model and good in the carotid artery model. The agreement
      between simultaneously acquired angiographic and IVUS images was very high for
      detecting increasing intra-aneurysmal coil mass (Spearman rank correlation
      coefficient of 0.98) and coil prolapse (83% agreement). CONCLUSION: IVUS guidance
      during aneurysm embolization may improve the procedure by providing intravascular
      aneurysmal measurements and visualization of devices used in the procedure.

PMID- 22157548
TI  - What we should know about the cellular and tissue response causing catheter
      obstruction in the treatment of hydrocephalus.
AB  - The treatment of hydrocephalus by cerebrospinal fluid shunting is plagued by
      ventricular catheter obstruction. Shunts can become obstructed by cells
      originating from tissue normal to the brain or by pathological cells in the
      cerebrospinal fluid for a variety of reasons. In this review, the authors examine
      ventricular catheter obstruction and identify some of the modifications to the
      ventricular catheter that may alter the mechanical and chemical cues involved in
      obstruction, including alterations to the surgical strategy, modifications to the
      chemical surface of the catheter, and changes to the catheter architecture. It is
      likely a combination of catheter modifications that will improve the treatment of
      hydrocephalus by prolonging the life of ventricular catheters to improve patient
      outcome.

PMID- 22157549
TI  - Morbidity and mortality of C2 fractures in the elderly: surgery and conservative
      treatment.
AB  - BACKGROUND: Closed C2 fractures commonly occur after falls or other trauma in the
      elderly and are associated with significant morbidity and mortality. Controversy
      exists as to best treatment practices for these patients. OBJECTIVE: To compare
      outcomes for elderly patients with closed C2 fractures by treatment modality.
      METHODS: We retrospectively reviewed 28 surgically and 28 nonsurgically treated
      cases of closed C2 fractures without spinal cord injury in patients aged 65 years
      of age or older treated at Stanford Hospital between January 2000 and July 2010.
      Comorbidities, fracture characteristics, and treatment details were recorded;
      primary outcomes were 30-day mortality and complication rates; secondary outcomes
      were length of hospital stay and long-term survival. RESULTS: Surgically treated
      patients tended to have more severe fractures with larger displacement. Charlson
      comorbidity scores were similar in both groups. Thirty-day mortality was 3.6% in
      the surgical group and 7.1% in the nonsurgical group, and the 30-day complication
      rates were 17.9% and 25.0%, respectively; these differences were not
      statistically significant. Surgical patients had significantly longer lengths of
      hospital stay than nonsurgical patients (11.8 days vs 4.4 days). Long-term median
      survival was not significantly different between groups. CONCLUSION: The 30-day
      mortality and complication rates in surgically and nonsurgically treated patients
      were comparable. Elderly patients faced relatively high morbidity and mortality
      regardless of treatment modality; thus, age alone does not appear to be a
      contraindication to surgical fixation of C2 fractures.

PMID- 22157550
TI  - A new method for modulating traumatic brain injury with mechanical tissue
      resuscitation.
AB  - BACKGROUND: Traumatic brain injuries remain a treatment enigma with devastating
      late results. As terminally differentiated tissue, the brain retains little
      capacity to regenerate, making early attempts to preserve brain cells after brain
      injury essential. OBJECTIVE: To resuscitate damaged tissue by modulating edema,
      soluble cytokines, and metabolic products in the "halo" of damaged tissue around
      the area of central injury that progressively becomes compromised. By re
      equilibrating the zone of injury milieu, it is postulated neurons in this area
      will survive and function. METHODS: Mechanical tissue resuscitation used
      localized, controlled, subatmospheric pressure directly to the area of controlled
      cortical impact injury and was compared with untreated injured controls and with
      sham surgery in a rat model. Functional outcome, T2 magnetic resonance imaging
      hyperintense volume, magnetic resonance imaging spectroscopy metabolite
      measurement, tissue water content, injury cavity area, and cortical volume were
      compared. RESULTS: There were significant differences between mechanical tissue
      resuscitation treated and untreated groups in levels of myoinositol, N
      acetylaspartate, and creatine. Treated animals had significantly less tissue
      swelling and density than the untreated animals. Nonviable brain tissue areas
      were smaller in treated animals than in untreated animals. Treated animals
      performed better than untreated animals in functional tests. Histological
      analysis showed the remaining viable ipsilateral cerebral area was 58% greater
      for treated animals than for untreated animals, and the cavity for treated
      animals was 95% smaller than for untreated animals 1 month after injury.
      CONCLUSION: Mechanical tissue resuscitation with controlled subatmospheric
      pressure can significantly modulate levels of excitatory amino acids and lactate
      in traumatic brain injury, decrease the water content and volume of injured
      brain, improve neuronal survival, and speed functional recovery.

PMID- 22157551
TI  - Avastin for breast cancer, 2005-2011: requiescat in pacem?

PMID- 22157552
TI  - Incorporation of crizotinib into the NCCN guidelines.

PMID- 22157553
TI  - The changing paradigm of treating pancreatic neuroendocrine tumors.

PMID- 22157554
TI  - Crizotinib and testing for ALK.
AB  - Crizotinib was recently approved by the US FDA for the treatment of advanced non
      small cell lung cancer (NSCLC) harboring the ALK (anaplastic lymphoma kinase)
      gene rearrangement. To ensure identification of patients most likely to benefit,
      the FDA approved crizotinib concurrently with a companion diagnostic test-the
      Vysis ALK Break Apart FISH Probe Kit. This kit was used in 1 of the 2 pivotal
      trials leading to the FDA approval of crizotinib and has become the gold standard
      for detecting ALK rearrangement in NSCLC. Although ALK FISH is clinically
      validated, the assay can be technically challenging and costly. Therefore, other
      diagnostic modalities are being explored, including immunohistochemistry (IHC)
      and reverse transcriptase-polymerase chain reaction. This article provides an
      overview of the diagnostic assays available for detecting ALK rearrangement. Each
      assay, including ALK FISH, has its strengths and weaknesses. Recent work with
      commercially available ALK antibodies suggests that IHC-based tests may represent
      a reliable and cost-effective screening strategy; however, large multicenter
      studies comparing IHC with FISH are needed to validate ALK IHC. While ALK FISH
      remains the current standard for diagnosing ALK positivity, large-scale screening
      of patients with newly diagnosed advanced NSCLC, as recommended by NCCN, may
      require development and validation of alternative screening strategies, such as
      combination IHC and FISH.

PMID- 22157555
TI  - Effort tracking metrics provide data for optimal budgeting and workload
      management in therapeutic cancer clinical trials.
AB  - Clinical trials operations struggle to achieve optimal distribution of workload
      in a dynamic data management and regulatory environment, and to achieve adequate
      cost recovery for personnel costs. The University of Michigan Comprehensive
      Cancer Center developed and implemented an effort tracking application to
      quantify data management and regulatory workload to more effectively assess and
      allocate work while improving charge capture. Staff recorded how much time they
      spend each day performing specific study-related and general office tasks.
      Aggregated data on staff use of the application from 2006 through 2009 were
      analyzed to gain a better understanding of what trial characteristics require the
      most data management and regulatory effort. Analysis revealed 4 major
      determinants of staff effort: 1) study volume (actual accrual), 2) study accrual
      rate, 3) study enrollment status, and 4) study sponsor type. Effort tracking also
      confirms that trials that accrued at a faster rate used fewer resources on a per
      patient basis than slow-accruing trials. In general, industry-sponsored trials
      required the most data management and regulatory support, outweighing other
      sponsor types. Although it is widely assumed that most data management efforts
      are expended while a trial is actively accruing, the authors learned that 25% to
      30% of a data manager's effort is expended while the study is either not yet open
      or closed to enrollment. Through the use of a data-driven effort tracking tool,
      clinical research operations can more efficiently allocate workload and ensure
      that study budgets are negotiated to adequately cover study-related expenses.

PMID- 22157556
TI  - NCCN Clinical Practice Guidelines Occult primary.
AB  - Occult primary tumors, or cancers of unknown primary (CUPs), are defined as
      histologically proven metastatic malignant tumors whose primary site cannot be
      identified during pretreatment evaluation. They have a wide variety of clinical
      presentations and a poor prognosis in most patients. Patients with occult primary
      tumors often present with general complaints, such as anorexia and weight loss.
      Clinical absence of primary tumor, early dissemination, aggressiveness, and
      unpredictability of metastatic pattern are characteristic of these tumors. Life
      expectancy is very short, with a median survival of 6 to 9 months. In most
      patients, occult primary tumors are refractory to systemic treatments, and
      chemotherapy is only palliative and does not significantly improve long-term
      survival. However, certain clinical presentations of these tumors are associated
      with a better prognosis. Special pathologic studies can identify subsets of
      patients with tumor types that are more responsive to chemotherapy. Treatment
      options should be individualized for this selected group of patients to achieve
      improved response and survival rates.

PMID- 22157557
TI  - Management of neuroendocrine tumors of unknown origin.
AB  - Neuroendocrine tumors (NETs) of unknown origin account for more than 10% of all
      NETs. Most of these tumors are poorly differentiated and, thus, very aggressive.
      Establishing the location of the primary tumor can be challenging. Workup of
      these NETs of unknown origin includes a thorough family history,
      immunohistochemistry, imaging, and OctreoScan. If the location of the primary
      malignancy is not determined, treatment is often initiated based on the grade and
      level of differentiation of the tumor, with well- and moderately differentiated
      tumors treated as carcinoid tumors, whereas poorly differentiated tumors are
      treated similarly to small cell tumors. Therapy is chosen based on symptoms and
      with the goal of debulking tumor when feasible and safe.

PMID- 22157558
TI  - Carcinoma of unknown primary: focused evaluation.
AB  - The management of carcinoma of unknown primary (CUP) has evolved over the past
      decade, with the advent of sophisticated imaging and pathologic tests. Especially
      in the era of tailored therapeutics, this presents both an opportunity and a
      challenge. For the initial workup of a patient with CUP, a focused search for the
      primary cancer based on clinical presentation is recommended. Exhaustive use of
      unnecessary imaging, invasive studies, and pathologic tests adds to patient
      discomfort, is associated with significant cost, and often has a low yield for
      detection of a primary cancer. Physicians should be able to justify the need for
      ancillary tests and how results may impact the comprehensive management of
      patients. Over the next several years, physicians also need to focus their
      efforts on refining CUP subsets (e.g., isolated nodal, osseous, carcinomatosis
      presentations) and leveraging selective genomics and proteomics techniques to
      eventually deliver validated new therapeutic approaches to patients. This will
      require creative approaches to clinical studies, including establishment of
      international CUP cooperative groups and innovative designs. Just as physicians
      need to be selective in their diagnostic approach, they also need to be selective
      in their research efforts as they continue to impact quality of life and survival
      for patients with CUP.

PMID- 22157559
TI  - Gene expression analysis and immunohistochemistry in evaluation of cancer of
      unknown primary: time for a patient-centered approach.
AB  - Molecular medicine is rapidly changing the diagnosis and management of cancer of
      unknown primary. The science, business, and economics of the genomic revolution
      have moved at such a pace that coordinating practical application of all
      available tools, such as gene expression analysis and immunohistochemistry, often
      seems to clash. In fact, very little work has been done to actively coordinate
      use of these techniques, each of which can be very resource-intensive. The
      Institute of Medicine proposed the STEEEP principles, a basic set of guidelines
      that maintain that the best patient care is safe, timely, effective, efficient,
      equitable, and patient-centered. Application of these principles will help lead
      to a better understanding of the most appropriate use of modern diagnostic
      modalities.

PMID- 22157562
TI  - Is hypertension a fatal disease today? Proceedings of a satellite symposium held
      during the 21st European Meeting on Hypertension and Cardiovascular Prevention
      Milan (Italy), June 17-20, 2011. Foreword.

PMID- 22157563
TI  - A new dimension in hypertension management with the amlodipine/perindopril
      combination.
AB  - Recent guidelines are consistent in acknowledging that most hypertensive patients
      need at least two drugs for optimal blood pressure (BP) control. Trial data are
      available to support the use of a renin-angiotensin system (RAS) blocker (ie, an
      angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker),
      plus a diuretic, a RAS blocker plus a calcium channel blocker (CCB), and a CCB
      plus a diuretic. The ACCOMPLISH trial demonstrated somewhat convincingly that an
      ACE inhibitor/CCB is superior to the same ACE inhibitor plus a thiazide. In the
      ASCOT trial, amlodipine/perindopril was superior to beta-blocker/thiazide in its
      effects on all major cardiovascular outcomes and new-onset diabetes. Further
      substudies of ASCOT provided plausible explanations for the benefits of
      amlodipine/perindopril strategy. In the CAFE substudy, amlodipine/perindopril was
      significantly more effective in the reduction of central BP as compared to
      atenolol/bendroflumethiazide, despite similar brachial BP reduction. More
      recently, analysis of long-term BP variability provided a further explanation for
      the reduction of cardiovascular events with amlodipine/perindopril in ASCOT.
      Thus, the combination of perindopril and amlodipine seems an ideal logical
      evidence-based pair of antihypertensive agents to select.

PMID- 22157564
TI  - Which patients benefit the most from the perindopril/amlodipine combination.
AB  - Fixed-dose combinations have been strongly endorsed by European guidelines for
      first-line and second-line treatment of hypertension. Among recommended
      combinations, that of an angiotensin-converting enzyme inhibitor and a calcium
      channel blocker stands out because the mechanisms of action of these two
      therapeutic classes are complementary, leading to enhanced efficacy. In the large
      multicentre ASCOT-BPLA trial, treatment based on the combination of amlodipine
      and perindopril significantly reduced the risk of cardiovascular and all-cause
      death, stroke, coronary events and procedures, new-onset diabetes, and new-onset
      renal impairment in a wide range of patients with hypertension and other
      cardiovascular risk factors, when compared with atenolol/thiazide-based therapy.
      The perindopril/amlodipine single-pill combination was developed based on
      guideline recommendations for combination treatment, the indications of each
      component, and ASCOT-BPLA trial data. Several studies in real-life settings show
      that a wide range of hypertensive patients, including everyday hypertensives with
      common risk factors, would benefit from the perindopril/amlodipine combination.

PMID- 22157565
TI  - Mortality patterns in hypertension.
AB  - Raised blood pressure (BP) is responsible for 7.6 million deaths per annum
      worldwide (13.5% of the total), more than any other risk factors. Around 54% of
      stroke and 47% of coronary heart disease are attributable to high BP. Over 80% of
      this burden occurs in low and middle income countries (LMIC). BP and
      cardiovascular mortality are rising rapidly in LMIC. Although age-specific BP and
      cardiovascular mortality are falling in developed nations, the overall number of
      cardiovascular death continues to rise in accord with the rapid aging of
      societies. Because of the continuous relationship between BP and cardiovascular
      deaths down to 115/75 mmHg, BP-related disease also contributes to cardiovascular
      death among people below the hypertensive threshold of 140/90 mmHg. Hypertension
      remains "the silent killer". Reductions in the burden of BP-related death require
      the parallel application of the population strategy at community level and the
      clinical strategy focusing on new and improved treatments for people with
      hypertension.

PMID- 22157566
TI  - Evidence for improvement in survival with antihypertensive combination treatment.
AB  - Hypertension constitutes a major risk factor for an array of cardiovascular
      diseases. Rates of morbidity and mortality related to its complications are high
      and remain an important concern in terms of public health. Improvement in
      cardiovascular outcomes and survival is an ultimate goal of the antihypertensive
      treatment. However, despite the wide range of available antihypertensive drugs,
      the rates of BP control are still insufficient. In most hypertensive patients,
      more than one antihypertensive compound is necessary to achieve goal levels of
      blood pressure. Assuming a greater antihypertensive effect may be obtained from
      two or more agents given in association, many combination therapies have been
      proposed and tested in a number of studies. The best clinical trial evidence
      comes from large outcome studies with an ACE inhibitor and dihydropyridine
      calcium antagonist combination, that of perindopril/amlodipine in the ASCOT trial
      in particular.

PMID- 22157567
TI  - Antibody persistence after a primary series of a new DTaP-IPV-Hep B-PRP-T
      combined vaccine or separate DTaP-IPV//PRP-T and hepatitis B vaccines at 2, 4,
      and 6 months of age and the effect of a subsequent DTaP-IPV//PRP-T booster
      vaccination at 18 months of age in healthy Argentinean infants.
AB  - OBJECTIVE: To assess antibody persistence after vaccination with a new, fully
      liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine at 18 months of age versus
      licensed DTaP-IPV//PRP-T and hepatitis B (Hep B) vaccines, and to assess the
      immunogenicity and safety of a subsequent DTaP-IPV//PRP-T booster. METHODS: A
      phase III, open-label, single-center study was conducted. Infants previously
      primed with 3 doses of DTaP-IPV-Hep B-PRP-T (Hexaxim: N = 232 [group 1]) or DTaP
      IPV//PRP-T and hepatitis B vaccine (Pentaxim + Engerix B Pediatrico: N = 226
      [group 2]) at 2, 4, and 6 months of age received a DTaP-IPV//PRP-T booster at 18
      months of age. Antibodies were measured before and 1 month after booster
      vaccination. Safety was evaluated from parental reports. Analyses were
      descriptive. RESULTS: Antibody persistence was high and similar in each group for
      each antigen except for Hep B, for which the percentage (95% confidence interval)
      of participants with a titer of >= 10 mIU/mL was higher in group 2 (99.5% [97.5%,
      100.0%]) than in group 1 (85.5% [80.3%, 89.8%]). Postbooster seroprotection
      (diphtheria, tetanus, inactivated poliovirus, polyribosyl-ribitol phosphate) and
      serconversion (pertussis toxoid, filamentous hemagglutinin) rates were high and
      similar in each group, and geometric mean antibody concentrations increased
      markedly in both groups. Safety after the booster vaccination was good and
      independent of the primary-series vaccine, although one serious adverse event of
      convulsions was considered to be vaccine related. CONCLUSIONS: The DTaP-IPV/PRP-T
      booster vaccination at 18 months of age was similarly immunogenic and well
      tolerated after primary-series vaccination with either the investigational
      hexavalent vaccine or the reference pentavalent vaccine. This confirms the
      suitability of a booster vaccination of DTaP-IPV//PRP-T after a primary series of
      the new DTaP-IPV-Hep B-PRP-T vaccine.

PMID- 22157568
TI  - Cellular effects after laser in situ keratomileusis flap formation with
      femtosecond lasers: a review.
AB  - PURPOSE: To provide an overview of the cellular effects of femtosecond laser in
      laser in situ keratomileusis flap formation. METHODS: Literature review. RESULTS:
      The IntraLase is the only femtosecond laser with sufficient histopathological and
      confocal studies to allow review of the cellular effects of laser application.
      Histopathological analyses have demonstrated that the energy per pulse and total
      energy delivered play important roles in the inflammatory reaction to the
      surgery. The IntraLase laser triggers cellular necrosis (death accompanied by the
      release of lysosomal enzymes and other components from membrane-bound
      intracellular compartments) in the corneal stroma surrounding the lamellar cut
      rather than apoptosis (gentler form of cell death in which most intracellular
      components remain confined to membrane-bound apoptotic bodies) that is
      predominant with the microkeratome. Necrosis is a more inflammatory form of cell
      death that attracts more inflammatory cells. This is likely why earlier
      femtosecond lasers, such as the 15-kHz IntraLase laser, which requires higher
      total energy delivery to cut a flap, are associated with more corneal
      inflammation and diffuse lamellar keratitis. The design of the 60-kHz IntraLase
      model allows for much lower energy delivery to cut the flap and, therefore, a
      substantial reduction in keratocyte necrosis to the point that the overall
      inflammatory response is not significantly different from the microkeratome.
      Histopathological analysis performed with the Femtec femtosecond laser noted
      little change in the corneal stromal structure. Confocal microcopy studies
      performed with the IntraLase laser showed keratocyte "activation" in the stroma
      and greater fibrotic scarring at the interface than that induced by a mechanical
      microkeratome. CONCLUSIONS: The morphologic alterations in the corneal stroma
      produced by currently available models of the IntraLase laser are comparable to
      those produced by mechanical microkeratomes. Advances that have resulted in a
      reduction in the total amount of energy delivered by the laser when it cuts the
      flap have resulted in a decrease in the inflammatory response associated with
      femtosecond flap formation to the point that it is indistinguishable from the
      microkeratome at the cellular level. Further study of each of the femtosecond
      laser models, including the 150-kHz IntraLase laser, is needed to fully
      characterize the corneal response to these lasers.

PMID- 22157569
TI  - Clinical features of anterior segment dysgenesis associated with congenital
      corneal opacities.
AB  - PURPOSE: Anterior segment dysgenesis is one of the main causes of congenital
      corneal opacities. In this study, we investigated the clinical features and
      visual outcomes of patients with anterior segment dysgenesis in a large number of
      cases. METHODS: The medical records of patients with congenital corneal opacities
      in relation to anterior segment dysgenesis seen in the National Center for Child
      Health and Development, Japan, between April 2002 and October 2009, were
      retrospectively studied. RESULTS: Records of 220 eyes of 139 patients were
      reviewed. Mean follow-up period was 5 years. Clinical diagnoses were Peters
      anomaly (72.7%), anterior staphyloma (11.4%), Rieger anomaly (7.7%), sclerocornea
      (6.4%), and others (1.8%). Visual acuity was measured in 61 patients. The best
      corrected visual acuity in the better eye of bilaterally involved patients was
      20/60 to 20/1000 (low vision according to the International Classification of
      Diseases, Ninth Revision, Clinical Modification) in 43.2% and less than 20/1000
      (legally blind) in 24.3%. Fundus examination was performed in 82 eyes, and
      disorders were seen in 12 (12 of 82; 14.6%). Systemic abnormalities were present
      in 35 patients (35 of 139; 25.2%); a family history was present in 5 patients (5
      of 139; 3.6%). Of the 160 eyes of 109 patients with Peters anomaly, 51 patients
      (51 of 109; 46.8%) had bilateral Peters anomaly, 30 (30 of 109; 27.5%) had fellow
      eyes that were normal, and 28 (28 of 109, 25.7%) showed other abnormal ocular
      findings in the fellow eye. CONCLUSIONS: Anterior segment dysgenesis shows
      diverse clinical features, various severities of corneal opacities, and visual
      outcomes. Further understanding of the disease as an abnormality during
      embryogenesis and neural crest cell differentiations may be required.

PMID- 22157570
TI  - Method for expressing clinical and statistical significance of ocular and corneal
      wave front error aberrations.
AB  - PURPOSE: The significance of ocular or corneal aberrations may be subject to
      misinterpretation whenever eyes with different pupil sizes or the application of
      different Zernike expansion orders are compared. A method is shown that uses
      simple mathematical interpolation techniques based on normal data to rapidly
      determine the clinical significance of aberrations, without concern for pupil and
      expansion order. METHODS: Corneal topography maps (TOMEY, Inc, Nagoya, Japan)
      from 30 normal corneas were collected, and the corneal wave front error was
      analyzed by Zernike polynomial decomposition into specific aberration types for
      pupil diameters of 3, 5, 7, and 10 mm and Zernike expansion orders of 6, 8, 10,
      and 12. Using this 4 * 4 matrix of pupil sizes and fitting orders, the best
      fitting 3-dimensional functions were determined for the mean and standard
      deviation of the root-mean-square error for specific aberrations. The functions
      were encoded into a software application to determine the significance of data
      acquired from nonnormal cases. RESULTS: The best-fitting functions for 6 types of
      aberrations were determined: defocus, astigmatism, prism, coma, spherical
      aberration, and all higher-order aberrations. A clinical screening method of
      color coding the significance of aberrations in normal, postoperative laser in
      situ keratomileusis, and keratoconus cases having different pupil sizes and
      different expansion orders is demonstrated. CONCLUSIONS: A method to calibrate
      wave front aberrometry devices using a standard sample of normal cases was
      devised. This method could be potentially useful in clinical studies involving
      patients with uncontrolled pupil sizes or in studies that compare data from
      aberrometers that use different Zernike fitting-order algorithms.

PMID- 22157571
TI  - Measurements of microkeratome cuts in donor corneas with ultrasound and optical
      coherence tomography.
AB  - PURPOSE: To evaluate optical coherence tomography (OCT) in the measurement of
      donor corneas in preparation for endothelial keratoplasty. METHODS: Donor corneas
      were imaged by OCT while immersed in preservation medium. Central corneal
      thickness (CCT) was measured by OCT from the Bowman layer to the endothelium. The
      corneas were then mounted on an artificial anterior chamber, and the epithelium
      was removed. Ultrasound pachymetry (USP) was used to measure CCT just before
      sectioning with a microkeratome. The central graft thickness (CGT) was measured
      by USP. The graft was then returned to the medium and imaged by OCT. RESULTS: The
      study included 154 donor corneas. The average CCT measured by OCT (550 +/- 63
      MUm) was thicker (P < 0.001) than that measured by USP (507 +/- 54 MUm).
      Similarly, the CGT measured by OCT (158 +/- 41 MUm) was thicker (P = 0.0005) than
      that measured by USP (153 +/- 38 MUm). The predictability of cut depth, as
      assessed by pooled standard deviation (SD), was better (P = 0.023) for USP (41
      MUm) compared with OCT (48 MUm). The graft was thicker (P < 0.001) peripherally
      than centrally in OCT images. The predictability of cut depth by OCT was better
      (P < 0.001) for corneas thinner than 600 MUm (SD = 45.6 MUm) compared with those
      thicker than 600 MUm (SD = 86.9 MUm). CONCLUSIONS: The donor corneal measurements
      by OCT were not as predictable as those by USP. The predictability of graft
      thickness, however, could be optimized using OCT to select for corneas thinner
      than 600 MUm and then using immediate precut USP to set the microkeratome depth.
      A graft thickness profile measured by OCT could be useful to the surgeon.

PMID- 22157572
TI  - Anti-VEGF therapy with bevacizumab for anterior segment eye disease.
AB  - PURPOSE: To review the current literature concerning the use of bevacizumab in
      treating neovascular disorders affecting the anterior segment ocular structures.
      METHODS: The authors reviewed the literature on anti-vascular endothelial growth
      factor (VEGF) therapy with bevacizumab for various anterior segment neovascular
      disorders that was indexed in MEDLINE (up to January 2011). RESULTS: Response to
      bevacizumab anti-VEGF therapy is variable, based on the amount of scarring, the
      chronicity and extent of corneal neovascularization, the disease process, and the
      medication formulation and its route of administration. Anti-VEGF agents are
      especially effective when administered early, before anatomical changes, such as
      corneal neovascularization and/or angle closure, are established.
      Neovascularization can recur if the ischemic or inflammatory process is not
      reversed, so eyes with long-standing diseases, such as autoimmune disorders that
      involve ongoing inflammation and VEGF production, seem to be less responsive to
      bevacizumab anti-VEGF therapy. For established neovascularization, combining anti
      VEGF agents with the removal of established vessels may be more effective than
      anti-VEGF therapy alone. Subconjunctival bevacizumab may be more appropriate for
      focal, deep, and peripheral neovascularization, whereas diffuse superficial
      neovascularization with central corneal involvement may be best treated via
      topical application. CONCLUSIONS: Besides the widely accepted use of bevacizumab
      in cancer therapy and chorioretinal neovascularization, the initial, striking,
      short-term response and patients' high tolerance of local bevacizumab therapy
      offer encouraging results for the potential role of anti-VEGF agents in treating
      anterior segment neovascular disorders. Controlled prospective trials are needed
      to establish the long-term safety, efficacy, and dosing guidelines for the use of
      anti-VEGF agents in anterior segment neovascularization.

PMID- 22157573
TI  - Changes of chloride channels in the lacrimal glands of a rabbit model of Sjogren
      syndrome.
AB  - PURPOSE: To test the hypothesis that expressions of Na-K-2Cl cotransporter-1
      (NKCC1), cystic fibrosis transmembrane conductance regulator (CFTR), and chloride
      channel 2 gamma subunit (ClC2gamma) in the lacrimal glands (LGs) of rabbits with
      induced autoimmune dacryoadenitis (IAD) are changed. METHODS: LGs were obtained
      from adult female rabbits with IAD and age-matched female control rabbits. LGs
      were processed for laser capture microdissection, real-time reverse transcription
      polymerase chain reaction, Western blot, and immunofluorescence. RESULTS: In
      rabbits with IAD, messenger RNA (mRNA) abundance and protein expressions of NKCC1
      and CFTR from whole LGs were significantly lower than those in controls. mRNA
      abundance of NKCC1, CFTR, and ClC2gamma from rabbits with IAD was significantly
      different from that in acinar and ductal cells from controls. NKCC1 was localized
      to the basolateral membranes of all acinar and ductal cells, with weaker staining
      intensity in ductal cells, and the staining pattern from rabbits with IAD
      appeared similar to that from controls. CFTR was found as punctate aggregates in
      the apical cytoplasm of all acinar and ductal cells, with the intensity in ductal
      cells much stronger and no significant difference between controls and rabbits
      with IAD. ClC2gamma was also localized to the apical cytoplasm as punctate
      aggregates of all acinar cells but not in ductal cells, and a similar staining
      pattern was observed in rabbits with IAD compared with control rabbits.
      CONCLUSIONS: Our data demonstrated significant changes of mRNA and protein
      expressions of NKCC1, CFTR, and ClC2gamma in rabbits with IAD, suggesting that
      these changes may contribute to the altered lacrimal secretion, particularly Cl
      transport, in rabbits with IAD.

PMID- 22157574
TI  - Diagnosis and treatment of ocular chronic graft-versus-host disease: report from
      the German-Austrian-Swiss Consensus Conference on Clinical Practice in chronic
      GVHD.
AB  - PURPOSE: Ocular chronic graft-versus-host disease (cGVHD) is one of the most
      frequent long-term complications after hematopoietic stem cell transplantation
      and is often associated with significant morbidity and reduced quality of life.
      METHODS: The German/Austrian/Swiss Consensus Conference on Clinical Practice in
      cGVHD aimed to summarize the currently available evidence for diagnosis and
      (topical) treatment and to summarize different treatment modalities of ocular
      cGVHD. The presented consensus was based on a review of published evidence and a
      survey on the current clinical practice including transplant centers from
      Germany, Austria, and Switzerland. RESULTS: Ocular cGVHD often affects the
      lacrimal glands, the conjunctiva, the lids (including meibomian glands), and the
      cornea but can also involve other parts of the eye such as the sclera. Up to now,
      there have been no pathognomonic diagnostic features identified. The main
      therapeutic aim in the management of ocular cGVHD is the treatment of
      inflammation and dryness to relieve patients' symptoms and to maintain ocular
      integrity and function. Therapy should be chosen in the context of the patient's
      overall condition, systemic immunosuppressive therapy, symptoms, ocular surface
      integrity, and inflammatory activity. The consensus conference proposed new
      grading criteria and diagnostic recommendations for general monitoring of
      patients with graft-versus-host-disease for use in clinical practice. CONCLUSION:
      The evidence levels for diagnosis and treatment of ocular cGVHD are low, and most
      of the treatment options are based on empirical knowledge. Topical
      immunosuppression, for example, with cyclosporine, represents a promising
      strategy to reduce inflammation and dryness in ocular cGVHD. Further clinical
      trials are necessary to elucidate risk factors for eye manifestation,
      complications, and visual loss and to evaluate staging criteria and diagnostic
      and therapeutic measures for ocular cGVHD.

PMID- 22157576
TI  - [Imaging of the kidney].
AB  - Imaging of the kidney relies on three main imaging modalities: ultrasound, CT
      scan and MRI, on one hand, and scintigraphy, on the other hand. First intent
      ultrasound provides anatomic/vascular and functional information. Tissue
      perfusion assessment using ultrasound can be improved using contrast agents.
      Renal ultrasound is particularly useful but remains operator and tumor/patient
      dependent (obese, ectopic kidney, type and site of tumor). It is cheap and does
      not irradiate. Ultrasound contrast agents can improve the sensitivity of
      ultrasound in many clinical situations. Intravenous urography has been replaced
      by CT scan. Multi-slice CT scan is indeed the main renal imaging modality: it
      allows for angiographic and urographic explorations. MRI provides anatomic and
      functional information. Renal failure must be looked for before performing CT
      scan or MRI so as to avoid iatrogenic complications. Severe renal failure is a
      contraindication to both. Each imaging modality has pros and cons and specific
      indications. CT scan is the mainstay of renal imaging provided that standardized
      injection protocols are used, that the dose is limited (low-dose protocol) and
      renal function is assessed. Dynamic renal scintigraphy can be used in situations
      where information on the function of each kidney is necessary.

PMID- 22157577
TI  - Regression does not significantly underestimate melanoma thickness.

PMID- 22157579
TI  - Antioxidant phenolic compounds of cassava (Manihot esculenta) from Hainan.
AB  - An activity-directed fractionation and purification process was used to isolate
      antioxidant components from cassava stems produced in Hainan. The ethyl acetate
      and n-butanol fractions showed greater DPPHand ABTS.+ scavenging activities than
      other fractions. The ethyl acetate fraction was subjected to column
      chromatography, to yield ten phenolic compounds: Coniferaldehyde (1), isovanillin
      (2), 6-deoxyjacareubin (3), scopoletin (4), syringaldehyde (5), pinoresinol (6),
      p-coumaric acid (7), ficusol (8), balanophonin (9) and ethamivan (10), which
      possess significant antioxidant activities. The relative order of DPPH.
      scavenging capacity for these compounds was ascorbic acid (reference) > 6 > 1 > 8
      > 10 > 9 > 3 > 4 > 7 > 5 > 2, and that of ABTS.+ scavenging capacity was 5 > 7 >
      1 > 10 > 4 > 6 > 8 > 2 > Trolox (reference compound) > 3 > 9. The results showed
      that these phenolic compounds contributed to the antioxidant activity  of
      cassava.

PMID- 22157580
TI  - Shortcut access to peptidosteroid conjugates: building blocks for solid-phase
      bile acid scaffold decoration by convergent ligation.
AB  - We present three versatile solid-supported scaffold building blocks based on the
      (deoxy)cholic acid framework and decorated with handles for further
      derivatization by modern ligation techniques such as click chemistry, Staudinger
      ligation or native chemical ligation. Straightforward procedures are presented
      for the synthesis and analysis of the steroid constructs. These building blocks
      offer a new, facile and shorter access route to bile acid-peptide conjugates on
      solid-phase with emphasis on heterodipodal conjugates with defined spatial
      arrangements. As such, we provide versatile new synthons to the toolbox for bile
      acid decoration.

PMID- 22157581
TI  - Synthesis and analgesic activity of some new pyrazoles and triazoles bearing a
      6,8-dibromo-2-methylquinazoline moiety.
AB  - 2-(6,8-Dibromo-2-methylquinazolin-4-yloxy)-acetohydrazide (4) was prepared by the
      reaction of 6,8-dibromo-2-methylbenzo-[d][1,3]oxazin-4-one with formamide to
      afford quinazolinone 2, followed by alkylation with ethyl chloroacetate to give
      the ester 3. Treatment of ester 3 with hydrazine hydrate and benzaldehyde
      afforded 4 and styryl quinazoline 5. The hydrazide was reacted with triethyl
      orthoformate, acetylacetone and ethyl acetoacetate and benzaldehyde derivatives
      to afford the corresponding pyrazoles 6, 7, 9 and hydrazone derivatives 10a-c.
      Cyclization of hydrazones 10a-c with thioglycolic acid afforded the thiazole
      derivatives 11a-c. Reaction of the hydrazide with isothiocyanate derivatives
      afforded hydrazinecarbothioamide derivatives 12a-c, which cyclized to triazole-3
      thiols and thiadiazoles 13a-c and 14a-c, respectively. Fusion of the hydrazide
      with phthalimide afforded the annelated compound 1,2,4-triazolo[3,4-a]isoindol-5
      one (15). The newly synthesized compounds were characterized by their spectral
      (IR, 1H-, 13C-NMR) data. Selected compounds were screened for analgesic activity.

PMID- 22157582
TI  - Information, discernment and learning:  for I am nothing if not critical.

PMID- 22157583
TI  - Contribution of circulating biomarkers to unravel the role of extracellular
      matrix in hypertensive cardiac remodelling.

PMID- 22157584
TI  - Hypertension and orthostatic hypotension in older patients.

PMID- 22157585
TI  - Does the combination of a renin inhibitor with a statin have potential for
      improved inhibition of atherosclerosis?

PMID- 22157586
TI  - Essential hypertension:  perspectives and future directions.

PMID- 22157587
TI  - Assessing antihypertensive treatment by real life data.

PMID- 22157588
TI  - A reappraisal of renin-angiotensin system blockade on microalbuminuria
      development:  do they offer anything unique?

PMID- 22157589
TI  - Modeling the impact of cardiovascular prevention strategies:  toward better
      information for public health decisions.

PMID- 22157590
TI  - Oxidative stress in the rostral ventrolateral medulla modulates excitatory and
      inhibitory inputs in spontaneously hypertensive rats.
AB  - OBJECTIVES: The rostral ventrolateral medulla (RVLM) of the brainstem and the
      paraventricular nucleus (PVN) of the hypothalamus play crucial roles in central
      cardiovascular regulation. In hypertensive rats, an imbalance of excitatory and
      inhibitory inputs to the RVLM enhances central sympathetic outflow. Increased
      reactive oxygen species (ROS) in the RVLM also contribute to sympathoexcitation,
      leading to hypertension. The aim of the present study was to elucidate whether
      ROS in the RVLM modulate synaptic transmission via excitatory and inhibitory
      amino acids and influence the excitatory inputs to the RVLM from the PVN in
      spontaneously hypertensive rats (SHRs). METHODS AND RESULTS: We transfected
      adenovirus vectors encoding the manganese superoxide dismutase (AdMnSOD) gene to
      scavenge ROS in the RVLM both in Wistar-Kyoto rats and SHRs. The decreases in
      blood pressure and renal sympathetic nerve activity (RSNA) evoked by injecting
      kynurenic acid, a glutamate receptor blocker, into the RVLM were attenuated, and
      the increases in blood pressure and RSNA evoked by injecting bicuculline, a gamma
      amino butyric acid (GABA) receptor blocker, into the RVLM were enhanced in
      AdMnSOD-transfected SHRs compared with adenovirus vectors encoding the beta
      galactosidase (AdLacZ) gene-transfected SHRs. Furthermore, the increases in blood
      pressure and RSNA evoked by injecting bicuculline into the PVN were attenuated in
      AdMnSOD-transfected SHRs compared with AdLacZ-transfected SHRs. CONCLUSION: These
      findings suggest that ROS in the RVLM enhance glutamatergic excitatory inputs and
      attenuate GABAergic inhibitory inputs to the RVLM, thereby increasing
      sympathoexcitatory input to the RVLM from the PVN in SHRs.

PMID- 22157591
TI  - A cost-utility analysis of hypertension treatment in Greece:  assessing the
      impact of age, sex and smoking status, on outcomes.
AB  - OBJECTIVES: To assess the cost-utility of hypertension treatment versus a
      hypothetical 'no-treatment' strategy in Greece. METHODS: A six-state Markov model
      simulated the occurrence of major cardiovascular events for hypertensive patients
      over a 20-year period. Baseline population consisted of a cohort of 1453 patients
      (46.92% men) that were followed up for a 1-year period, during which health
      resource use and clinical characteristics of hypertension were documented. Age,
      sex and smoking status - specific transition probabilities in the model - were
      estimated via the HellenicSCORE and Framingham risk equations. The analysis
      followed a third-party payer perspective. RESULTS: Incremental cost-effectiveness
      ratios (ICERs) of treatment versus no treatment were 3539&OV0556;/quality
      adjusted life year (QALY), 3986&OV0556;/QALY, 3957&OV0556;/QALY and
      5485&OV0556;/QALY gained for men smokers, men nonsmokers, women smokers and women
      nonsmokers, respectively. ICERs became more favorable with an increase in the
      years of treatment and advanced age of treatment initiation across all study
      groups. The probabilistic sensitivity analysis showed that the base-case scenario
      results were cost-effective for an implicit 30 000&OV0556;/QALY threshold at
      97.4, 95.2, 94.8, and 86% of the 10 000 Monte Carlo simulations for men smokers,
      men nonsmokers, women smokers and women nonsmokers, respectively. CONCLUSION: In
      the case of hypertension, one of the most prevalent and modifiable diseases/risk
      factors, that is accompanied by large-scale costs, the above analysis
      demonstrates that treatment is a highly cost-effective intervention that should
      be further supported at the patient and the system level.

PMID- 22157592
TI  - Different methods to present the effect of blood pressure on cardiovascular
      diseases by Cox regression.

PMID- 22157593
TI  - Creating awareness and change in 2012.

PMID- 22157594
TI  - [Radiosensitivity assays of normal tissues].
AB  - Radiotherapy allows locoregional control with systemic impact in some
      indications. Technologic advances decrease the dose received by normal tissues
      leading to a low crude number of late side effects near to 5%. Intrinsic
      radiosensitivity are still of interest in this context of high level of
      technology and optimized treatments. Assays of radiosensitivity are detailed in
      this article arguing the negative results but also the perspectives.

PMID- 22157595
TI  - Mitomycin C: biological effects and use in refractive surgery.
AB  - PURPOSE: To provide an overview of the safety and efficacy of mitomycin C (MMC)
      as adjuvant therapy after refractive surgery procedures. METHODS: Literature
      review. RESULTS: Over the past 10 years, MMC has been used by refractive surgeons
      to prophylactically decrease haze after surface ablation procedures and
      therapeutically in the treatment of preexisting haze. Development of MMC
      treatments has had a significant role in the revival of surface ablation
      techniques. We reviewed the literature regarding mechanism of action of MMC, its
      role in modulating wound healing after refractive surgery, and its safety and
      efficacy as adjuvant therapy applied after primary photorefractive keratectomy
      surgery or after photorefractive keratectomy re-treatment after laser in situ
      keratomileusis and other corneal surgeries and disorders. The drug is a potent
      mitotic inhibitor that effectively blocks keratocyte activation, proliferation,
      and myofibroblast differentiation. Many studies have suggested that MMC is safe
      and effective in doses used by anterior surface surgeons, although there continue
      to be concerns regarding long-term safety. After initial depletion of anterior
      keratocytes, keratocyte density seems to return to normal 6 to 12 months after
      the use of MMC when corneas are examined with the confocal microscope. Most
      clinical studies found no difference between preoperative and postoperative
      corneal endothelial cell densities when MMC 0.02% was applied during refractive
      surgery, with exposure time of 2 minutes or less. CONCLUSIONS: After more than 10
      years of use, MMC has been found to be effective when used for prevention and
      treatment of corneal haze. Questions remain regarding optimal treatment
      parameters and long-term safety.

PMID- 22157596
TI  - Prediction of HIV-1 coreceptor usage (tropism) by sequence analysis using a
      genotypic approach.
AB  - Maraviroc (MVC) is the first licensed antiretroviral drug from the class of
      coreceptor antagonists. It binds to the host coreceptor CCR5, which is used by
      the majority of HIV strains in order to infect the human immune cells (Fig. 1).
      Other HIV isolates use a different coreceptor, the CXCR4. Which receptor is used,
      is determined in the virus by the Env protein (Fig. 2). Depending on the
      coreceptor used, the viruses are classified as R5 or X4, respectively. MVC binds
      to the CCR5 receptor inhibiting the entry of R5 viruses into the target cell.
      During the course of disease, X4 viruses may emerge and outgrow the R5 viruses.
      Determination of coreceptor usage (also called tropism) is therefore mandatory
      prior to administration of MVC, as demanded by EMA and FDA. The studies for MVC
      efficiency MOTIVATE, MERIT and 1029 have been performed with the Trofile assay
      from Monogram, San Francisco, U.S.A. This is a high quality assay based on
      sophisticated recombinant tests. The acceptance for this test for daily routine
      is rather low outside of the U.S.A., since the European physicians rather tend to
      work with decentralized expert laboratories, which also provide concomitant
      resistance testing. These laboratories have undergone several quality assurance
      evaluations, the last one being presented in 2011. For several years now, we have
      performed tropism determinations based on sequence analysis from the HIV env-V3
      gene region (V3). This region carries enough information to perform a reliable
      prediction. The genotypic determination of coreceptor usage presents advantages
      such as: shorter turnover time (equivalent to resistance testing), lower costs,
      possibility to adapt the results to the patients' needs and possibility of
      analysing clinical samples with very low or even undetectable viral load (VL),
      particularly since the number of samples analysed with VL < 1000 copies/MUl
      roughly increased in the last years (Fig. 3). The main steps for tropism testing
      (Fig. 4) demonstrated in this video: Collection of a blood sample Isolation of
      the HIV RNA from the plasma and/or HIV proviral DNA from blood mononuclear cells
      Amplification of the env region Amplification of the V3 region Sequence reaction
      of the V3 amplicon Purification of the sequencing samples Sequencing the purified
      samples Sequence editing Sequencing data interpretation and tropism prediction.

PMID- 22157597
TI  - Effectiveness of sulfasalazine and methotrexate in 1102 DMARD-naive patients with
      early RA.
AB  - OBJECTIVE: To compare baseline characteristics, responses and drug survival in
      patients with early RA starting SSZ or MTX in a real-life setting. METHODS: The
      analyses included DMARD-naive patients with RA (disease duration <= 1 year)
      starting SSZ or MTX. Three- and 6-month effectiveness was compared by unadjusted
      analysis and with adjustment for propensity score quintile. In addition,
      effectiveness in SSZ- and MTX-treated patients matched for RF status and baseline
      DAS-28 was compared. RESULTS: SSZ-treated patients (n = 175) had lower baseline
      disease activity than patients treated with MTX (n = 927) [mean 28-joint DAS (DAS
      28) 4.4 vs 5.0, P < 0.001], and were less often RF positive (50 vs 61%, P =
      0.006). Six-month mean DeltaDAS-28 was smaller with SSZ than MTX (-1.0 vs -1.5, P
      = 0.003); the difference was not significant after adjustment for propensity
      score quintile (P = 0.36). For SSZ/MTX, 3-month ACR50 and European League Against
      Rheumatism (EULAR) good responses were 9/23% (P < 0.001) and 24/31% (P = 0.14),
      respectively. Three-year drug survival was superior for MTX (P < 0.001) and
      estimated 1-year survival rates were 42/75% for SSZ/MTX. In patients matched for
      baseline DAS-28 and RF, mean DeltaDAS-28 (MTX -1.2, P = 0.55 vs SSZ) and EULAR
      good responses (39 vs 37%, P = 0.74) were similar at 6 months; drug survival was
      superior for MTX (P < 0.001). CONCLUSION: Patients treated with SSZ as first
      DMARD were more often RF negative and had lower baseline disease activity. Drug
      survival was superior for MTX, and effectiveness was greater with MTX than with
      SSZ although the difference was reduced when adjusting for differences in
      baseline characteristics.

PMID- 22157598
TI  - Streptococcal hypersensitivity reloaded: severe inflammatory syndrome in Behcet's
      disease following 23-valent polysaccharide Streptococcus pneumoniae vaccine.

PMID- 22157599
TI  - Altered metabolism of low-density lipoprotein and very-low-density lipoprotein
      remnant in autosomal recessive hypercholesterolemia: results from stable isotope
      kinetic study in vivo.
AB  - BACKGROUND: Autosomal recessive hypercholesterolemia (ARH) exhibits different
      responsiveness to statins compared with that in homozygous familial
      hypercholesterolemia (FH). However, few data exist regarding lipoprotein
      metabolism of ARH. Therefore, we aimed to clarify lipoprotein metabolism,
      especially the remnant lipoprotein fractions of ARH before and after statin
      therapy. METHODS AND RESULTS: We performed a lipoprotein kinetic study in an ARH
      patient and 7 normal control subjects, using stable isotope methodology (10 mg/kg
      of [(2)H(3)]-leucine). These studies were performed at baseline and after the 20
      mg daily dose of atorvastatin. Tracer/tracee ratio of apolipoprotein B (apoB) was
      determined by gas chromatography/mass spectrometry and fractional catabolic rates
      (FCR) were determined by multicompartmental modeling, including remnant
      lipoprotein fractions. FCR of low-density lipoprotein (LDL) apoB of ARH was
      significantly lower than those of control subjects (0.109 versus 0.450+/-0.122
      1/day). In contrast, the direct removal of very-low-density lipoprotein remnant
      was significantly greater in ARH than those in control subjects (47.5 versus 2+/
      2%). Interestingly, FCR of LDL apoB in ARH dramatically increased to 0.464 1/day,
      accompanying reduction of LDL cholesterol levels from 8.63 to 4.22 mmol/L after
      treatment with atorvastatin of 20 mg/d for 3 months. CONCLUSIONS: These results
      demonstrate that ARH exhibits decreased LDL clearance associated with decreased
      FCR of LDL apoB and increased clearance for very-low-density lipoprotein remnant.
      We suggest that increased clearance of remnant lipoprotein fractions could
      contribute to the great responsiveness to statins, providing new insights into
      the lipoprotein metabolism of ARH and the novel pharmacological target for
      LDLRAP1.

PMID- 22157600
TI  - Bad cell disease.

PMID- 22157601
TI  - Temporary human experience.

PMID- 22157602
TI  - Letter from the president of PSNCB.

PMID- 22157603
TI  - Evolving role of alloderm in breast surgery.
AB  - The adjunctive use of acellular dermal matrices in breast surgery is expanding.
      The purpose of this article is to provide an overview of the various applications
      of acellular dermal matrices in breast surgery, the benefits and complications
      associated with their use, and best practices to optimize outcomes using a human
      acellular dermal matrix (AlloDerm [LifeCell Corp., Branchburg, NJ]) as an
      example.

PMID- 22157604
TI  - A historical, clinical, and ethical overview of the emerging science of facial
      transplantation.
AB  - In the past 5 years, a total of 16 facial transplantation surgeries have been
      performed in France, China, Spain, and the United States. Facial transplantation
      has become a surgical option in clinical situations in which soft tissue and bone
      loss is accompanied by severe cosmetic, sensory, and functional deficiencies due
      to disease, trauma, or congenital malformations. With the introduction of facial
      tissue transplantation surgery came complex clinical, technological, and ethical
      patient care issues. These complex issues included determining patient selection
      criteria, refining donor tissue procurement techniques, predicting expected
      functional outcomes, appreciating the limitations of obtaining a fully informed
      consent for an innovative procedure, and deliberating the immunological response
      and postoperative immunosuppressant requirements of the recipient. In addition,
      psychological implications for the patient, societal consequences, and ethical
      concerns have been discussed. The short-term results have been positive. Results
      to date indicate that the clinical, technical, and immunological patient care
      issues in this emerging science appear to mirror those of other reconstructive
      and organ transplantation procedures. The long-term physical, emotional, and
      psychological effects on the recipient patient, as well as long-term consequences
      to the donor's family, are yet to be validated.

PMID- 22157606
TI  - Self-esteem and patients' satisfaction after deep inferior epigastric perforator
      flap breast reconstruction.
AB  - The objective of this article is to assess the impact of deep inferior epigastric
      perforator (DIEP) flap breast reconstruction on self-esteem and to analyze the
      correlation between aesthetic outcome and self-esteem. Global self-esteem was
      evaluated using the Rosenberg Self-Esteem Scale in 31 patients who underwent DIEP
      flap breast reconstructions. A study-specific questionnaire and photographic
      evaluation were used by the patient, the plastic surgeon, and the oncological
      surgeon to measure satisfaction with the aesthetic outcome. Patients'
      satisfaction and self-esteem were analyzed for any existing correlation. Overall
      patients' satisfaction had a mean score of 6.55 (range, 0-10) on the Patient
      Satisfaction Questionnaire. A mean score of 32.48 (range, 10-40) was found on the
      Rosenberg Self-Esteem Scale. More than 80% of patients were content with their
      decision to undergo this procedure and would recommend this to a friend. Surgeons
      tended to rate the aesthetic outcome better than patients. Patients' satisfaction
      and self-esteem were found to be positively correlated. Patients are generally
      content with the outcome of primary DIEP flap breast reconstruction. The
      favorable aesthetic result of this procedure has a beneficial effect on patients'
      self-esteem.

PMID- 22157608
TI  - Cardiac arrest and the 2010 advanced cardiac life support guidelines--part IV.
AB  - The chance of a successful outcome with any cardiac arrest is prompt initiation
      of hands-only compression at a rate of at least 100 per min, to a depth of 2
      in.,with full chest recoil, and no more than a 10-s interruption of compressions.
      The priority, regardless of being in a private clinic or in a facility using a
      team approach,is to start compressions and maintain effective compressions with
      minimal interruptions. Most cardiac arrests are related to ventricular
      fibrillation and the chance of successfully defibrillating this rhythm is highest
      at the beginning of the arrest. For every minute a patient is in ventricular
      fibrillation, his or her chance of survival greatly decreases (Traverset al.,
      2010). This is why it is extremely important to defibrillate immediately. Once a
      patient has return of spontaneous circulation,postresuscitation care needs to be
      implemented. The biggest reason for a patient to develop ventricular fibrillation
      is an acute coronary syndrome, and this is why the new guidelines have outlined
      transferring a post arrest patient to a cardiac catheterization laboratory to
      perform an emergency angiogram and angioplasty. Part of this post arrest
      management also includes therapeutic hypothermia in those patients who remain
      comatose after return of spontaneous circulation. This article has reviewed a
      case study of a postoperative patient who developed ventricular fibrillation and
      the priorities of care according to the 2010 ACLS guidelines. Watch for more ACLS
      based case studies in upcoming articles.

PMID- 22157609
TI  - Infected? Or not?
AB  - The criteria described earlier should be considered when the classic signs of
      wound infection do not appear. These criteria should also be considered in the
      presence of delayed wound healing as delayed wound healing should produce a high
      suspicion of an existing wound infection.The importance of the early recognition
      and suspicion of wound infection should not be underestimated because of the high
      economic burden of prolonged treatment and human suffering.The challenge to the
      practitioner lies in possessing knowledge and ability to recognize the state of a
      wound in relation to the bacterial continuum and intervene appropriately.

PMID- 22157610
TI  - Psychological characteristics and outcomes of elective cosmetic surgery patients:
      the influence of cosmetic surgery history.
AB  - The early cosmetic surgery literature suggested that individuals re-presenting
      for aesthetic surgical procedures (referred to as "insatiable patients") display
      poorer psychological functioning and satisfaction with surgical outcomes than
      those who request one procedure. The aim of the study was to compare 284 patients
      with and without a history of cosmetic procedures on demographic characteristics,
      appearance concerns, expectations of surgery, psychosocial dysfunction, and
      postoperative dissatisfaction. There were few differences between the groups,
      suggesting that the group of patients with a history of aesthetic surgeries did
      not represent the population that has been described as "surgery insatiable."
      Post hoc analyses of subgroups of patients with a history of surgeries also
      revealed few differences except for lower self-esteem and postoperative
      satisfaction. Further research is required to fully explore the applicability of
      the "insatiable patient" label in the context of increasing societal acceptance
      of cosmetic surgery.

PMID- 22157611
TI  - Do I need my own malpractice insurance?

PMID- 22157612
TI  - Closed-suction drain systems in the plastic surgery patient.

PMID- 22157614
TI  - Multiplex ligation-dependent probe amplification equals fluorescence in-situ
      hybridization for the identification of patients at risk for metastatic disease
      in uveal melanoma.
AB  - In uveal melanoma, loss of chromosome 3 and gain of chromosome 8q are associated
      with a high risk of metastasis. In this study, we validated the use of multiplex
      ligation-dependent probe amplification (MLPA) in detecting patients at risk for
      metastatic disease in comparison with the predictive power of fluorescence in
      situ hybridization (FISH). For 64 uveal melanoma samples, the MLPA results of
      chromosome 3 and 8 were compared with the results obtained by FISH. For seven
      samples, a single nucleotide polymorphism array was performed to clarify
      discrepancies. Clinical information together with the histopathology and
      chromosomal aberrations of chromosomes 1, 3, 6, and 8 were evaluated for
      correlation with the patients' prognosis. Loss of chromosome 3, loss or gain of
      8p, and gain of 8q, found with MLPA, correlated with a significantly lower
      disease-free survival (P<0.001). On the basis of the clinical outcome, 12
      patients would have been classified incorrectly using MLPA results of chromosomes
      3 and 8. FISH results led to the same incorrect classification. Four patients
      with abnormalities of chromosomes 3 and 8 in the tumor, detected with MLPA, are
      still alive without metastasis. Eight patients without concurrent aberrations of
      chromosomes 3 and 8 in the tumors died due to metastasis. The sensitivity of MLPA
      to detect patients at risk for metastatic disease is higher than with the results
      obtained with FISH (0.795 vs. 0.692). The specificity is equal for both
      techniques (0.840). MLPA is able to detect patients at risk for metastasis using
      the results for chromosomes 3 and 8. There is no significant difference in the
      predictive power of MLPA compared with FISH.

PMID- 22157615
TI  - Butyrylcholinesterase is associated with beta-amyloid plaques in the transgenic
      APPSWE/PSEN1dE9 mouse model of Alzheimer disease.
AB  - Histochemical analysis of Alzheimer disease (AD) brain tissues indicates that
      butyrylcholinesterase (BuChE) is present in beta-amyloid (Abeta) plaques. The
      role of BuChE in AD pathology is unknown, but an animal model developing similar
      BuChE-associated Abeta plaques could provide insights. The APPSWE/PSEN1dE9
      transgenic mouse (ADTg), which develops Abeta plaques, was examined to determine
      if BuChE associates with these plaques, as in AD. We found that in mature ADTg
      mice, BuChE activity associated with Abeta plaques. The Abeta-, thioflavin-S- and
      BuChE-positive plaques mainly accumulated in the olfactory structures, cerebral
      cortex, hippocampal formation, amygdala, and cerebellum. No plaques were stained
      for acetylcholinesterase activity. The distribution and abundance of plaque
      staining in ADTg closely resembled many aspects of plaque staining in AD.
      Butyrylcholinesterase staining consistently showed fewer plaques than were
      detected with Abeta immunostaining but a greater number of plaques than were
      visualized with thioflavin-S. Double-labeling experiments demonstrated that all
      BuChE-positive plaques were Abeta positive, whereas only some BuChE-positive
      plaques were thioflavin-S positive. These observations suggest that BuChE is
      associated with a subpopulation of Abeta plaques and may play a role in AD plaque
      maturation. A further study of this animal model could clarify the role of BuChE
      in AD pathology.

PMID- 22157616
TI  - Lentiviral infection of rhesus macaques causes long-term injury to cortical and
      hippocampal projections of prostaglandin-expressing cholinergic basal forebrain
      neurons.
AB  - The simian immunodeficiency virus (SIV) macaque model resembles human
      immunodeficiency virus-acquired immunodeficiency syndrome (AIDS) and associated
      brain dysfunction. Altered expression of synaptic markers and transmitters in
      neuro-AIDS has been reported, but limited data exist for the cholinergic system
      and lipid mediators such as prostaglandins. Here, we analyzed cholinergic basal
      forebrain neurons with their telencephalic projections and the rate-limiting
      enzymes for prostaglandin synthesis, cyclooxygenase isotypes 1 and 2 (COX1 and
      COX2) in the brains of SIV-infected macaques with or without encephalitis and
      antiretroviral therapy and uninfected controls.Cyclooxygenase isotype 1, but not
      COX2, was coexpressed with markers of cholinergic phenotype, that is, choline
      acetyltransferase and vesicular acetylcholine transporter (VAChT), in basal
      forebrain neurons of monkey, as well as human, brain. Cyclooxygenase isotype 1
      was decreased in basal forebrain neurons in macaques with AIDS versus uninfected
      and asymptomatic SIV-infected macaques. The VAChT-positive fiber density was
      reduced in frontal, parietal, and hippocampal-entorhinal cortex. Although brain
      SIV burden and associated COX1- and COX2-positive mononuclear and endothelial
      inflammatory reactions were mostly reversed in AIDS-diseased macaques that
      received 6-chloro-2',3'-dideoxyguanosine treatment, decreased VAChT-positive
      terminal density and reduced cholinergic COX1 expression were not. Thus, COX1
      expression is a feature of primate cholinergic basal forebrain neurons; it may be
      functionally important and a critical biomarker of cholinergic dysregulation
      accompanying lentiviral encephalopathy. These results further imply that
      insufficiently prompt initiation of antiretroviral therapy in lentiviral
      infection may lead to neurostructurally unremarkable but neurochemically
      prominent irreversible brain damage.

PMID- 22157617
TI  - Fig4 expression in the rodent nervous system and its potential role in preventing
      abnormal lysosomal accumulation.
AB  - The phosphatase FIG4 regulates the concentration of phosphatidylinositol 3,5
      diphosphate (PI3,5P2), a molecule critical for endosomal/lysosomal membrane
      trafficking and neuron function. We investigated Fig4 expression in the
      developing CNS of mice and rats using Western blot, real-time polymerase chain
      reaction, and morphological techniques in situ and in vitro and after spinal cord
      injury. Fig4 was expressed at a high levels throughout development in myelinating
      cells, particularly Schwann cells, and dorsal root ganglia sensory neurons. Fig4
      protein and mRNA in CNS neurons were markedly diminished in adult versus
      embryonal animals. Spinal cord hemisection induced upregulation of Fig4 in adult
      spinal cord tissues that was associated with accumulation of lysosomes in neurons
      and glia. This accumulation appeared similar to the abnormal lysosomal storage
      observed in dorsal root ganglia of young fig4-null mice. The results suggest that
      Fig4 is involved in normal neural development and the maintenance of peripheral
      nervous system myelin. We speculate that adequate levels of Fig4 may be required
      to prevent neurons and glia from excessive lysosomal accumulation after injury
      and in neurodegeneration.

PMID- 22157618
TI  - Early microglial activation precedes neuronal loss in the brain of the Cstb-/-
      mouse model of progressive myoclonus epilepsy, EPM1.
AB  - Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is a hereditary
      neurodegenerative disorder caused by mutations in the cystatin B (CSTB) gene
      encoding an inhibitor of cysteine proteases. Here, we provide the first detailed
      description of the onset and progression of pathologic changes in the CNS of Cstb
      deficient (Cstb) mice. Our data reveal early and localized glial activation in
      brain regions where neuron loss subsequently occurs. These changes are most
      pronounced in the thalamocortical system, with neuron loss occurring first within
      the cortex and only subsequently in the corresponding thalamic relay nucleus.
      Microglial activation precedes the emergence of myoclonia and is followed by
      successive astrocytosis and selective neuron loss. Neuron loss was not detected
      in thalamic relay nuclei that displayed no glial activation. Microglia showed
      morphologic changes during disease progression from that of phagocytic brain
      macrophages in young animals to having thickened branched processes in older
      animals. These novel data on the timing of pathologic events in the CSTB
      deficient brain highlight the potential role of glial activation at the initial
      stages of the disease. Determining the precise sequence of the neurodegenerative
      events in Cstb mouse brains will lay the basis for understanding the
      pathophysiology of EPM1.

PMID- 22157619
TI  - Frequent infection of cortical neurons by JC virus in patients with progressive
      multifocal leukoencephalopathy.
AB  - The human polyomavirus JC (JCV) infects glial cells and causes progressive
      multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, in
      immunosuppressed individuals. The extent of JCV infection of neurons is unclear.
      We determined the prevalence and pattern of JCV infection in gray matter (GM) by
      immunostaining in archival brain samples of 49 PML patients and 109 control
      subjects. Among PML patients, 96% had demyelinating lesions in white matter and
      at the gray-white junction (GWJ); 57% had them in the GM. Most JCV-infected cells
      in GWJ and GM were glia, but JCV also infected neurons in PML lesions at the GWJ
      of 54% and GM of 50% patients and in GM outside areas of demyelination in 11% of
      patients. The JCV regulatory T antigen (Ag) was expressed more frequently in
      cortical neurons than the VP1 capsid protein. None of the control subjects
      without PML had any cells expressing JCV proteins. Thus, the cerebral cortex
      often harbors demyelinating lesions of PML, and JCV infection of cortical neurons
      is frequent in PML patients. The predominance of T Ag over VP1 expression
      suggests a restrictive infection in neurons. These results indicate that JCV
      infection of cerebral cortical neurons is a previously under appreciated
      component of PML pathogenesis.

PMID- 22157620
TI  - BRAF alterations in primary glial and glioneuronal neoplasms of the central
      nervous system with identification of 2 novel KIAA1549:BRAF fusion variants.
AB  - Recent studies highlight the importance of BRAF alterations resulting in mitogen
      activated protein kinase (MAK/ERK) pathway activation in low-grade CNS tumors. We
      studied 106 low-grade CNS neoplasms in a cohort of primarily pediatric patients
      to identify the prevalence and clinicopathologic significance of these
      alterations. Polymerase chain reaction testing identified KIAA1549:BRAF fusions
      in 51 (48%) tumors overall, including 42 (60%) pilocytic astrocytomas, 4 (17%)
      unclassifiable low-grade gliomas, 4 (36%) low-grade glioneuronal/neuroepithelial
      tumors, 0 (of 5) pleomorphic xanthoastrocytomas, 0 (of 4) diffuse astrocytomas
      (World Health Organization grade II), and 1 (of 3, 33%) pilomyxoid astrocytoma.
      KIAA1549:BRAF gene fusions confirmed by sequencing included the previously
      reported ones involving exons 1-16/9-18 (49%), 1-15/9-18 (35%), and 1-16/11-18
      (8%) and 2 fusions with novel breakpoints: 1-15/11-18 (6%) and 1-17/10-18 (1%).
      DNA sequencing identified BRAF mutations in 8% of tumors. BRAF mutations were
      absent. KIAA1549:BRAF fusions were significantly more frequent in infratentorial
      (57%) and optic pathway (59%) tumors versus supratentorial (19%) tumors (p =
      0.001). We did not identify significantly improved progression-free survival in
      tumors with fusions. In summary, KIAA1549:BRAF fusions predominate in pilocytic
      astrocytomas but are also present in some low-grade unclassifiable gliomas and
      glioneuronal tumors. The prognostic and therapeutic significance of this
      alteration is unclear and merits further study.

PMID- 22157621
TI  - Clinical stratification of glioblastoma based on alterations in retinoblastoma
      tumor suppressor protein (RB1) and association with the proneural subtype.
AB  - A recent study of CDK4/6 inhibitors in glioblastoma (GBM) xenografts identified
      retinoblastoma tumor suppressor protein RB1 status as a determinant of tumor
      therapeutic efficacy. Because of the need for clinically applicable RB1 testing,
      we assessed the utility of 2 complementary methods for determining RB1 status in
      GBM. Using fluorescence in situ hybridization (FISH) and immunohistochemistry
      (IHC), we analyzed 34 GBMs that had also undergone molecular characterization as
      part of The Cancer Genome Atlas (TCGA). By IHC, 4 tumors (11.8%) had complete
      loss of RB protein expression, including 2 with homozygous deletion of RB1 by
      FISH and 1 with hemizygous deletion of RB1 by FISH combined with a novel nonsense
      mutation in RB1. Consistent with these results, in an independent set of 51 GBMs
      tested by IHC, we demonstrated loss of RB1 protein in 5 (9.8%). In GBM molecular
      subtype analysis of TCGA data, complete loss of RB1 transcript expression was
      seen in 18 (10.6%) of 170 tumors, and these were highly enriched for, but not
      exclusive to, the proneural subtype (p < 0.01). These data support the use of IHC
      for determining RB1 status in clinical GBM specimens and suggest that RB1
      alterations may be more common in certain GBM subgroups.

PMID- 22157622
TI  - The importance of 10q status in an outcomes-based comparison between 1p/19q
      fluorescence in situ hybridization and polymerase chain reaction-based
      microsatellite loss of heterozygosity analysis of oligodendrogliomas.
AB  - 1p/19q codeletion is a favorable prognostic marker of oligodendrogliomas.
      Although fluorescence in situ hybridization (FISH) and microsatellite-based
      polymerase chain reaction (PCR) for loss of heterozygosity (LOH) are common
      methods to test for 1p/19q codeletion, it is unclear which test is better at
      prognostic stratification. This study analyzed outcomes of 111 oligodendrogliomas
      with both 1p/19q FISH and LOH done at the time of diagnosis. Overall concordance
      between the 2 assays was 81.1%. In grade III oligodendrogliomas, LOH was better
      than FISH at survival stratification (p < 0.0001 for LOH vs p = 0.02 for FISH),
      although increasing the stringency of FISH interpretation criteria improved
      concordance and prognostic power. Oligodendrogliomas that were 1p/19q-codeleted
      by FISH but also had 10q LOH were negative for 1p/19q codeletion by PCR analysis
      in more than 70% of cases, with very poor survival in the grade III subset. Thus,
      although PCR-based LOH is a better stratifier of 1p/19q status, FISH still has
      clinical and prognostic utility, especially if 10q data can be incorporated.

PMID- 22157624
TI  - New immune therapy targets tumor-associated environment: from bone marrow to
      tumor site.

PMID- 22157623
TI  - Liver fibrosis: mechanisms of immune-mediated liver injury.
AB  - Liver fibrosis and its end-stage consequence, cirrhosis, represent the final
      common pathway of virtually all chronic liver diseases. Research into hepatic
      stellate cell activation, imbalance of the extracellular matrix synthesis and
      degradation and the contribution of cytokines and chemokines has further
      elucidated the mechanisms underlying fibrosis. Furthermore, clarification of
      changes in host adaptive and innate immune systems has accelerated our
      understanding of the association between liver inflammation and fibrosis.
      Continued elucidation of the mechanisms of hepatic fibrosis has provided a
      comprehensive model of fibrosis progression and regression. This review
      summarizes the current concepts of improvements that have been made in the field
      of fibrosis.

PMID- 22157625
TI  - Hospital and neurodevelopmental outcomes of extremely low-birth-weight infants
      with necrotizing enterocolitis and spontaneous intestinal perforation.
AB  - OBJECTIVE: We sought to determine the incidence of necrotizing enterocolitis
      (NEC) and spontaneous intestinal perforation (SIP) in surviving extremely low
      birth-weight (ELBW, <1000 g birth weight) infants and to establish the impact of
      NEC on outcomes by hospital discharge and at 18 to 22 months adjusted age in a
      large, contemporary, population-based practice. STUDY DESIGN: Hospital outcome
      data for all ELBW infants born in the greater Cincinnati region from 1998 to 2009
      were extracted from the National Institute of Child Health Neonatal Research
      Network Database. Neurodevelopmental outcome at 18 to 22 months was assessed
      using Bayley Scales of Infant Development-II scores for Mental Developmental
      Index and Psychomotor Developmental Index. Multivariable logistic regression was
      used and adjusted odds ratios reported to control for confounders. RESULT: From
      1998 to 2009, ELBW infants accounted for 0.5% of the 352 176 live-born infants in
      greater Cincinnati. The incidence of NEC was 12%, with a 50% case-fatality rate.
      Death before discharge, morbid complications of prematurity and
      neurodevelopmental impairment were all increased among infants diagnosed with
      NEC. Infants with surgical NEC and SIP had a higher incidence of death, but long
      term neurodevelopmental outcomes were not different comparing surviving ELBW
      infants with medical NEC, surgical NEC and SIP. CONCLUSION: Although ELBW infants
      comprise a very small proportion of live-born infants, those who develop NEC and
      SIP are at an increased risk for death, morbid complications of prematurity and
      neurodevelopmental impairment. No significant differences in neurodevelopmental
      outcomes were observed between the medical and surgical NEC and SIP groups.

PMID- 22157626
TI  - Antenatal antibiotic exposure in preterm infants with necrotizing enterocolitis.
AB  - OBJECTIVE: To determine whether an association exists between antenatal
      antibiotic exposure and incidence of necrotizing enterocolitis (NEC) in low birth
      weight infants. STUDY DESIGN: A retrospective case-control study was performed on
      all infants with a diagnosis of NEC born at our institition between 1988 and
      2006. Medical histories of all infants with a diagnosis of NEC >=Bell's stage IIA
      and matched controls without NEC were reviewed. Maternal and neonatal
      characteristics were compared using the Mantel-Haenszel chi-square procedure, and
      logistic regression models were constructed to account for confounding. RESULT:
      Clinical data for 97 matched pairs were analyzed. The adjusted odds ratio (OR)
      for antenatal exposure to ampicillin was significantly greater for infants who
      developed NEC (OR 2.3, 95% confidence interval 1.1, 4.8, P=0.003) than for
      control infants. CONCLUSION: Infants who developed NEC were more likely to have a
      history of in utero exposure to ampicillin in the immediate antepartum period
      than infants who did not develop NEC.

PMID- 22157627
TI  - The effects of vestibular stimulation rate and magnitude of acceleration on
      central pattern generation for chest wall kinematics in preterm infants.
AB  - OBJECTIVE: To examine the role of vestibular inputs on respiratory and oromotor
      systems in healthy preterm infants. STUDY DESIGN: A total of 27 preterm infants
      were quasi-randomly assigned to either the VestibuGlide treatment or control
      groups. VestibuGlide infants were held in a developmentally supportive position,
      given a pacifier and received a series of vestibular stimuli, counterbalanced
      across rate and acceleration conditions, 15 min 3 times per day for 10 days. The
      control infants were also held in a developmentally supportive position, given a
      pacifier for 15 min 3 times per day for 10 days but did not receive the
      VestibuGlide stimulation. RESULT: A multi-level regression model revealed that
      treatment infants increased their respiratory rate in response to vestibular
      stimulus, and that the highest level of vestibular acceleration delivered to the
      infants (0.51 ms(-2)) resulted in a significant increase in breaths per minute.
      CONCLUSION: Vestibular stimulation delivered to preterm infants before scheduled
      feeds effectively modulates respiratory rate and resets the respiratory central
      pattern generator.

PMID- 22157628
TI  - The coagulation system of extremely preterm infants: influence of perinatal risk
      factors on coagulation.
AB  - OBJECTIVE: Little is known about the influence of preterm delivery and perinatal
      risk factors on development and expression of the coagulation system in extremely
      preterm infants. The objective of this study was to determine reference values
      for the components of the coagulation system at the first day of life in
      extremely preterm infants. STUDY DESIGN: Components of the coagulation system
      were examined retrospectively in 132 extremely preterm infants. Patients were
      grouped according to clinical criteria for preterm delivery: group A: maternal
      indication; group B: uteroplacental dysfunction; group C: systemic inflammation.
      RESULT: Levels of coagulation factors VII and X rose with increasing gestational
      age, whereas fibrinogen and coagulation factors II, V and VIII remained constant.
      Levels of factors V and VIII were higher than those of vitamin K-dependent
      factors. If preterm delivery was caused by placental disorder (group B) or
      chorioamnionitis (group C), levels of factor II, VIII and X were significantly
      lower, whereas factor V and VII levels did not differ. In group C fibrinogen
      levels in group C were higher compared with group A. CONCLUSION: Identification
      of perinatal risk factors may help to define patients at risk of bleeding
      disorders.

PMID- 22157629
TI  - Abstracts of the British Geriatrics Society Autumn Meeting. October 12-14, 2011.
      Brighton, United Kingdom.

PMID- 22157631
TI  - Treatment options for insomnia.
AB  - Complaints of insomnia, including reports of difficulty initiating and remaining
      asleep, are often reported to primary healthcare providers. Nurse practitioners
      must be prepared to screen patients for this common sleep disorder as well as
      understand the latest treatment options for optimal patient outcomes.

PMID- 22157630
TI  - Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage
      Plasmodium infection.
AB  - Infection of erythrocytes with Plasmodium species induces clinical malaria.
      Parasite-specific CD4(+) T cells correlate with lower parasite burdens and
      severity of human malaria and are needed to control blood-stage infection in
      mice. However, the characteristics of CD4(+) T cells that determine protection or
      parasite persistence remain unknown. Here we show that infection of humans with
      Plasmodium falciparum resulted in higher expression of the inhibitory receptor PD
      1 associated with T cell dysfunction. In vivo blockade of the PD-1 ligand PD-L1
      and the inhibitory receptor LAG-3 restored CD4(+) T cell function, amplified the
      number of follicular helper T cells and germinal-center B cells and plasmablasts,
      enhanced protective antibodies and rapidly cleared blood-stage malaria in mice.
      Thus, chronic malaria drives specific T cell dysfunction, and proper function can
      be restored by inhibitory therapies to enhance parasite control.

PMID- 22157632
TI  - Loss of reactivity in intravitreal anti-VEGF therapy: tachyphylaxis or tolerance?

PMID- 22157633
TI  - Femtosecond laser-assisted lock-and-key shaped penetrating keratoplasty.

PMID- 22157634
TI  - Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male
      half-siblings with autism.
AB  - Autism is a neurodevelopmental disorder with a strong genetic component to
      susceptibility. In this study, we report the molecular characterization of an
      apparent de-novo 281 kb duplication of chromosome 2p25.3 in two male half
      siblings with autism. The 2p25.3 duplication was first identified through a low
      density microarray, validated with fluorescent in-situ hybridization, and
      duplication breakpoints were delineated using an Affymetrix 6.0 single-nucleotide
      polymorphism microarray. The fluorescent in-situ hybridization results validated
      the novel copy number variant and revealed the mother to be mosaic, with ~33% of
      her lymphoblast cells carrying the duplication. Therefore, the duplication was
      transmitted through the mechanism of germline mosaicism. In addition, duplication
      breakpoints were refined and showed that PXDN is fully duplicated, whereas seven
      exons of the terminal portion of the 25 exon gene MYT1L are within the duplicated
      region. MYT1L, a gene predominately expressed in the brain, has recently been
      linked with other neuropsychiatric illness such as schizophrenia and depression.
      Results from this study indicate that the 2p25.3 duplication disrupting PXDN and
      MYT1L is a potential autism-causing variant in the pedigree reported here and
      should receive further consideration as a candidate for autism.

PMID- 22157635
TI  - Lack of association between the regulator of G-protein signaling 4 (RGS4)
      rs951436 polymorphism and schizophrenia.

PMID- 22157636
TI  - [Reirradiation for recurrent or second primary head and neck cancers].
AB  - Recurrences or second primary head and neck cancers meant, for a long time,
      therapeutic dead ends. Surgery was the standard treatment, but could only be
      achieved in 25% of the patients. The GETTEC-GORTEC (99-01) randomized trial
      showed that radiochemotherapy improved disease-free survival for a highly
      selected population. For inoperable patients, three options can be discussed:
      supportive care only, chemotherapy or radiotherapy with or without chemotherapy.
      The EXTREME protocol showed that combining platinum, 5FU and cetuximab improved
      overall survival for recurrent or metastatic forms. This is certainly the best
      option for advanced forms, which are not accessible to radiotherapy. Concerning
      radiotherapy, only one randomized trial compared chemoradiotherapy to
      chemotherapy alone using methotrexate. The overall survival, the main objective
      in this study, was not improved, however, the enrollment was incomplete and
      included many advanced stage tumors. Other articles are based on Vokes' initial
      work of radiochemotherapy delivered in split-course over a period of 11 weeks.
      All conventional and conformational radiotherapy series showed improved local
      control and disease-free survival rates, but at the expense of acute and late
      toxicities demanding a drastic patients selection. New radiotherapy techniques
      such as intensity modulated radiotherapy (IMRT) and stereotactic body
      radiotherapy (SBRT) have reduced toxicities with a likely oncological results
      improvement, offering treatments which are spread over six to seven weeks for
      IMRT and two weeks for SBRT. The better treatment tolerance allows an increasing
      number of eligible patients. The main future objective will be to define the
      specific IMRT and SBRT indications.

PMID- 22157637
TI  - The effects of personality traits on quality of life.
AB  - OBJECTIVE: The aim of this study was to investigate the impact of women's
      personality traits and some sociodemographic variables on quality of life (QoL).
      METHODS: This cross-sectional and correlational study was conducted among 320
      Turkish women aged between 45 and 64 years who attended the Menopausal
      Polyclinic. Data were collected from the Turkish version of the Cervantes
      Personality Scale and the Turkish version of the Menopause-Specific Quality of
      Life Questionnaire. RESULTS: The mean (SD) age of the participants was 51.8 (5.3)
      years. The average (SD) age since menopause was found to be 46 (3.3) years. The
      menopausal QoL was correlated with education status, income level, working
      status, exercise routine, chronic health problems, family's/friends' support, and
      negative life events. Logistic regression analyses showed that the QoL in
      vasomotor, psychological, and sexual domains were 6.1, 9.2, and 11.4 times,
      respectively, lower in neurotic women than in emotionally stable women. In
      addition, the QoL in sexual domains were 3.3 times lower in introverted women
      than in extraverted women. CONCLUSION: These findings indicate that higher levels
      of introversion and higher levels of neuroticism lead to lower QoL among
      postmenopausal women. The results of this study support the hypothesis that
      personality would play an important role in women's QoL during the transition
      period of menopause.

PMID- 22157638
TI  - Imaging pheromone sensing in a mouse vomeronasal acute tissue slice preparation.
AB  - Peter Karlson and Martin Luscher used the term pheromone for the first time in
      1959 to describe chemicals used for intra-species communication. Pheromones are
      volatile or non-volatile short-lived molecules secreted and/or contained in
      biological fluids, such as urine, a liquid known to be a main source of
      pheromones. Pheromonal communication is implicated in a variety of key animal
      modalities such as kin interactions, hierarchical organisations and sexual
      interactions and are consequently directly correlated with the survival of a
      given species. In mice, the ability to detect pheromones is principally mediated
      by the vomeronasal organ (VNO), a paired structure located at the base of the
      nasal cavity, and enclosed in a cartilaginous capsule. Each VNO has a tubular
      shape with a lumen allowing the contact with the external chemical world. The
      sensory neuroepithelium is principally composed of vomeronasal bipolar sensory
      neurons (VSNs). Each VSN extends a single dendrite to the lumen ending in a large
      dendritic knob bearing up to 100 microvilli implicated in chemical detection.
      Numerous subpopulations of VSNs are present. They are differentiated by the
      chemoreceptor they express and thus possibly by the ligand(s) they recognize. Two
      main vomeronasal receptor families, V1Rs and V2Rs, are composed respectively by
      240 and 120 members and are expressed in separate layers of the neuroepithelium.
      Olfactory receptors (ORs) and formyl peptide receptors (FPRs) are also expressed
      in VSNs. Whether or not these neuronal subpopulations use the same downstream
      signalling pathway for sensing pheromones is unknown. Despite a major role played
      by a calcium-permeable channel (TRPC2) present in the microvilli of mature
      neurons TRPC2 independent transduction channels have been suggested. Due to the
      high number of neuronal subpopulations and the peculiar morphology of the organ,
      pharmacological and physiological investigations of the signalling elements
      present in the VNO are complex. Here, we present an acute tissue slice
      preparation of the mouse VNO for performing calcium imaging investigations. This
      physiological approach allows observations, in the natural environment of a
      living tissue, of general or individual subpopulations of VSNs previously loaded
      with Fura-2AM, a calcium dye. This method is also convenient for studying any GFP
      tagged pheromone receptor and is adaptable for the use of other fluorescent
      calcium probes. As an example, we use here a VG mouse line, in which the
      translation of the pheromone V1rb2 receptor is linked to the expression of GFP by
      a polycistronic strategy.

PMID- 22157639
TI  - Use of patient-reported outcomes to improve the predictive accuracy of clinician
      reported adverse events.

PMID- 22157641
TI  - Climate change, allergies, and asthma.

PMID- 22157640
TI  - Patient self-reports of symptoms and clinician ratings as predictors of overall
      cancer survival.
AB  - BACKGROUND: The National Cancer Institute's Common Terminology Criteria for
      Adverse Events (NCI-CTCAE) reporting system is widely used by clinicians to
      measure patient symptoms in clinical trials. The European Organization for
      Research and Treatment of Cancer's Quality of Life core questionnaire (EORTC QLQ
      C30) enables cancer patients to rate their symptoms related to their quality of
      life. We examined the extent to which patient and clinician symptom scoring and
      their agreement could contribute to the estimation of overall survival among
      cancer patients. METHODS: We analyzed baseline data regarding six cancer symptoms
      (pain, fatigue, vomiting, nausea, diarrhea, and constipation) from a total of
      2279 cancer patients from 14 closed EORTC randomized controlled trials. In each
      trial that was selected for retrospective pooled analysis, both clinician and
      patient symptom scoring were reported simultaneously at study entry. We assessed
      the extent of agreement between clinician vs patient symptom scoring using the
      Spearman and kappa correlation statistics. After adjusting for age, sex,
      performance status, cancer severity, and cancer site, we used Harrell concordance
      index (C-index) to compare the potential for clinician-reported and/or patient
      reported symptom scores to improve the accuracy of Cox models to predict overall
      survival. All P values are from two-sided tests. RESULTS: Patient-reported scores
      for some symptoms, particularly fatigue, did differ from clinician-reported
      scores. For each of the six symptoms that we assessed at baseline, both clinician
      and patient scorings contributed independently and positively to the predictive
      accuracy of survival prognostication. Cox models of overall survival that
      considered both patient and clinician scores gained more predictive accuracy than
      models that considered clinician scores alone for each of four symptoms: fatigue
      (C-index = .67 with both patient and clinician data vs C-index = .63 with
      clinician data only; P <.001), vomiting (C-index = .64 vs .62; P = .01), nausea
      (C-index = .65 vs .62; P < .001), and constipation (C-index = .62 vs .61; P =
      .01). CONCLUSION: Patients provide a subjective measure of symptom severity that
      complements clinician scoring in predicting overall survival.

PMID- 22157642
TI  - Work prognosis of complex regional pain syndrome type I:  multicenter
      retrospective study on the determinants and time to return to work.

PMID- 22157643
TI  - Respiratory symptoms necessitating spirometry among soldiers with
      Iraq/Afghanistan war lung injury.

PMID- 22157645
TI  - Prevention of immunoglobulin e sensitization to latex in health care workers
      after reduction of antigen exposures.

PMID- 22157647
TI  - Shiftwork and changes in health behaviors.
AB  - OBJECTIVE: We studied the associations between exposure to shiftwork and changes
      in health behaviors. METHODS: We used questionnaire data from 2062 women enrolled
      in a cohort study a few weeks before graduating as health care
      helpers/assistants. We analyzed whether shiftwork in 2005 was associated with
      changes in smoking habits, level of physical activity, or weight from 2004 to
      2006. RESULTS: Fixed nightwork was associated with higher odds of smoking
      relapse, lower odds of smoking cessation, and lower odds of becoming physically
      active. Two and three shifts with nightwork were associated with lower odds of
      weight gain. Fixed evening work and two shifts without nightwork were not
      associated with changes in health behaviors. CONCLUSION: Changes in health
      behaviors may mediate some of the association between fixed nightwork and health
      outcomes.

PMID- 22157650
TI  - Cardiac myosin binding protein C insufficiency leads to early onset of mechanical
      dysfunction.
AB  - BACKGROUND: Decreased expression of cardiac myosin binding protein C (cMyBPC) as
      a result of genetic mutations may contribute to the development of hypertrophic
      cardiomyopathy (HCM); however, the mechanisms that link cMyBPC expression and HCM
      development, especially contractile dysfunction, remain unclear. METHODS AND
      RESULTS: We evaluated cardiac mechanical function in vitro and in vivo in young
      mice (8-10 weeks of age) carrying no functional cMyBPC alleles (cMyBPC(-/-)) or 1
      functional cMyBPC allele (cMyBPC(+/-)). Skinned myocardium isolated from cMyBPC(
      /-) hearts displayed significant accelerations in stretch activation cross-bridge
      kinetics. Cardiac MRI studies revealed severely depressed in vivo left
      ventricular (LV) magnitude and rates of LV wall strain and torsion compared with
      wild-type (WT) mice. Heterozygous cMyBPC(+/-) hearts expressed 23+/-5% less
      cMyBPC than WT hearts but did not display overt hypertrophy. Skinned myocardium
      isolated from cMyBPC(+/-) hearts displayed small accelerations in the rate of
      stretch induced cross-bridge recruitment. MRI measurements revealed reductions in
      LV torsion and circumferential strain, as well reduced circumferential strain
      rates in early systole and diastole. CONCLUSIONS: Modest decreases in cMyBPC
      expression in the mouse heart result in early-onset subtle changes in cross
      bridge kinetics and in vivo LV mechanical function, which could contribute to the
      development of HCM later in life.

PMID- 22157651
TI  - Immunosuppressive exosomes from TGF-beta1 gene-modified dendritic cells attenuate
      Th17-mediated inflammatory autoimmune disease by inducing regulatory T cells.

PMID- 22157652
TI  - Semaphorin signaling in angiogenesis, lymphangiogenesis and cancer.
AB  - Angiogenesis, the formation of new blood vessels from preexisting vasculature, is
      essential for many physiological processes, and aberrant angiogenesis contributes
      to some of the most prevalent human diseases, including cancer. Angiogenesis is
      controlled by delicate balance between pro- and anti-angiogenic signals. While
      pro-angiogenic signaling has been extensively investigated, how developmentally
      regulated, naturally occurring anti-angiogenic molecules prevent the excessive
      growth of vascular and lymphatic vessels is still poorly understood. In this
      review, we summarize the current knowledge on how semaphorins and their
      receptors, plexins and neuropilins, control normal and pathological angiogenesis,
      with an emphasis on semaphorin-regulated anti-angiogenic signaling circuitries in
      vascular and lymphatic endothelial cells. This emerging body of information may
      afford the opportunity to develop novel anti-angiogenic therapeutic strategies.

PMID- 22157654
TI  - The kinase Pyk2 is involved in renal fibrosis by means of mechanical stretch
      induced growth factor expression in renal tubules.
AB  - Unilateral ureteral obstruction is a well-established experimental model of
      progressive renal fibrosis. We tested whether mechanical stretch and subsequent
      renal tubular distension might lead to renal fibrosis by first studying renal
      tubular epithelial cells in culture. We found that mechanical stretch induced
      reactive oxygen species that in turn activated the cytoplasmic proline-rich
      tyrosine kinase-2 (Pyk2). This kinase is abundantly expressed in tubular
      epithelial cells where it is activated by several stimuli. Using mice with
      deletion of Pyk2 we found that the expression of transforming growth factor-beta1
      induced by mechanical stretch in renal tubular epithelial cells was significantly
      reduced. The expression of connective tissue growth factor was also reduced in
      the Pyk2(-/-) mice. We also found that expression of connective tissue growth
      factor was independent of transforming growth factor-beta1, but dependent on the
      Rho-associated coiled-coil forming protein kinase pathway. Thus, Pyk2 may be an
      important initiating factor in renal fibrosis and might be a new therapeutic
      target for ameliorating renal fibrosis.

PMID- 22157653
TI  - Endosome-mediated retrograde axonal transport of P2X3 receptor signals in primary
      sensory neurons.
AB  - Neurotrophins and their receptors adopt signaling endosomes to transmit
      retrograde signals. However, the mechanisms of retrograde signaling for other
      ligand/receptor systems are poorly understood. Here, we report that the signals
      of the purinergic (P)2X(3) receptor, an ATP-gated ion channel, are retrogradely
      transported in dorsal root ganglion (DRG) neuron axons. We found that Rab5, a
      small GTPase, controls the early sorting of P2X(3) receptors into endosomes,
      while Rab7 mediates the fast retrograde transport of P2X(3) receptors.
      Intraplantar injection and axonal application into the microfluidic chamber of
      alpha, beta-methylene-ATP (alpha, beta-MeATP), a P2X selective agonist, enhanced
      the endocytosis and retrograde transport of P2X(3) receptors. The alpha, beta
      MeATP-induced Ca(2+) influx activated a pathway comprised of protein kinase C,
      rat sarcoma viral oncogene and extracellular signal-regulated protein kinase
      (ERK), which associated with endocytic P2X(3) receptors to form signaling
      endosomes. Disruption of the lipid rafts abolished the alpha, beta-MeATP-induced
      ERK phosphorylation, endocytosis and retrograde transport of P2X(3) receptors.
      Furthermore, treatment of peripheral axons with alpha, beta-MeATP increased the
      activation level of ERK and cAMP response element-binding protein in the cell
      bodies of DRG neurons and enhanced neuronal excitability. Impairment of either
      microtubule-based axonal transport in vivo or dynein function in vitro blocked
      alpha, beta-MeATP-induced retrograde signals. These results indicate that P2X(3)
      receptor-activated signals are transmitted via retrogradely transported endosomes
      in primary sensory neurons and provide a novel signaling mechanism for ligand
      gated channels.

PMID- 22157655
TI  - Glomerular hyperfiltration and increased glomerular filtration surface are
      associated with renal function decline in normo- and microalbuminuric type 2
      diabetes.
AB  - The prevalence of glomerular hyperfiltration in type 2 diabetic patients varies
      widely. Here we studied whether glomerular hyperfiltration in diabetic
      nephropathy in type 2 patients is related to renal structural changes and
      predicts the functional development of diabetic nephropathy. Thirty normo- or
      microalbuminuric type 2 diabetic patients having a renal biopsy were followed
      every 6 months for a mean of 6.2 years. The glomerular filtration rate (GFR) at
      the time of biopsy, determined by iohexol clearance, correlated with filtration
      surface per glomerulus, but no other quantitative microscopic morphometric
      parameter. The filtration surface was positively associated with the decrease in
      GFR during the first year but not associated in subsequent years following the
      renal biopsy. The GFR showed a statistically significant linear decrease in 9 of
      the 30 patients; however, slopes of the regression lines were almost zero in 11
      patients. The GFR increased and decreased in a parabolic manner in two patients.
      Seven of the nine patients with a statistically significant decline in renal
      function did not show any appreciable worsening of albuminuria, while two
      patients developed persistent proteinuria. Thus, in renal biopsy-proven normo- or
      microalbuminuric type 2 diabetic patients, glomerular hyperfiltration is closely
      associated with an increased glomerular filtration surface. An elevated GFR
      predicts its subsequent decline, which may occur without worsening of
      albuminuria.

PMID- 22157656
TI  - Increased risk of death and de novo chronic kidney disease following reversible
      acute kidney injury.
AB  - Acute kidney injury increases mortality risk among those with established chronic
      kidney disease. In this study we used a propensity score-matched cohort method to
      retrospectively evaluate the risks of death and de novo chronic kidney disease
      after reversible, hospital-associated acute kidney injury among patients with
      normal pre-hospitalization kidney function. Of 30,207 discharged patients alive
      at 90 days, 1610 with reversible acute kidney injury that resolved within the 90
      days were successfully matched across multiple parameters with 3652 control
      patients who had not experienced acute kidney injury. Median follow-up was 3.3
      and 3.4 years (injured and control groups, respectively). In Cox proportional
      hazard models, the risk of death associated with reversible acute kidney injury
      was significant (hazard ratio 1.50); however, adjustment for the development of
      chronic kidney injury during follow-up attenuated this risk (hazard ratio 1.18).
      Reversible acute kidney injury was associated with a significant risk of de novo
      chronic kidney disease (hazard ratio 1.91). Thus, a resolved episode of hospital
      associated acute kidney injury has important implications for the longitudinal
      surveillance of patients without preexisting, clinically evident kidney disease.

PMID- 22157657
TI  - Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the
      confusion.
AB  - Membranoproliferative glomerulonephritis (MPGN) denotes a general pattern of
      glomerular injury that is easily recognized by light microscopy. With additional
      studies, MPGN subgrouping is possible. For example, electron microscopy resolves
      differences in electron-dense deposition that are classically referred to as MPGN
      type I (MPGN I), MPGN II, and MPGN III, while immunofluorescence typically
      detects immunoglobulins in MPGN I and MPGN III but not in MPGN II. All three MPGN
      types stain positive for complement component 3 (C3). Subgrouping has led to
      unnecessary confusion, primarily because immunoglobulin-negative MPGN I and MPGN
      III are more common than once recognized. Together with MPGN II, which is now
      called dense deposit disease, immunoglobulin-negative, C3-positive glomerular
      diseases fall under the umbrella of C3 glomerulopathies (C3G). The evaluation of
      immunoglobulin-positive MPGN should focus on identifying the underlying trigger
      driving the chronic antigenemia or circulating immune complexes in order to begin
      disease-specific treatment. The evaluation of C3G, in contrast, should focus on
      the complement cascade, as dysregulation of the alternative pathway and terminal
      complement cascade underlies pathogenesis. Although there are no disease-specific
      treatments currently available for C3G, a better understanding of their
      pathogenesis would set the stage for the possible use of anti-complement drugs.

PMID- 22157658
TI  - Meta-analytic study of implant survival following sinus augmentation.
AB  - OBJECTIVES: To evaluate graft types used for maxillary sinus augmentation and
      review success rates of dental implants inserted in these areas, analyzing the
      graft materials used, implant surface types and the moment of implant placement.
      STUDY DESIGN: A meta-analytic study reviewing articles on sinus augmentation
      published during the last ten years. RESULTS: 3,975 implants placed in sinus
      augmentations (with bony windows) were registered, of which 3,749 implants
      survived, a survival rate of 94.3%. CONCLUSIONS: When performing sinus
      augmentation, bone substitute materials are just as effective as autologous bone,
      whether used alone or in combination with autologous bone. Implant surface
      treatments can have an important effect on implant survival and it would appear
      that roughened surfaces are the best option. When implants are inserted
      simultaneously to grafting, a higher failure rate can be expected.

PMID- 22157659
TI  - Meta-analysis of the increase in height in maxillary  sinus elevations with
      osteotome.
AB  - OBJECTIVES: To compare the different variations of sinus elevation techniques
      with osteotomes, to evaluate the increase in height achieved, and to quantify the
      osseointegration periods and the success rates for the implants placed. STUDY
      DESIGN: A meta-analytic study with descriptive statistics was carried out on
      sinus elevations using osteotomes, analyzing a total of 11 articles published
      between the years 2003 and 2008. RESULTS: Summers' classic technique for
      performing sinus elevations with osteotomes differs from the current techniques
      being used with respect to the use of drills, the manner in which the sinus floor
      is fractured and how the sinus membrane is lifted, and especially on the type of
      graft used-the most current tendency being not to use a graft. The maximum gain
      in height is 4.62 mm, and the minimum gain in height is 2.07 mm, starting with a
      maximum residual bone height of 8.8 mm and a minimum of 4.1 mm. The
      osseointegration period is 4.9 months and the success rate is 95.5%. CONCLUSIONS:
      Performing sinus elevations with osteotomes is a predictable technique that
      enables achieving an increase in bone height and successful results, similar to
      those of other techniques used, in the placement of implants.

PMID- 22157660
TI  - Influence of oral health on mucositis in patients undergoing hematopoietic
      progenitor cell transplantation (HPCT).
AB  - AIMS: To establish whether or not the state of patient oral health can influence
      the occurrence and/or severity of oral mucositis during hematopoietic progenitor
      cell transplantation (HPCT). MATERIALS AND METHODS: The study included 72
      patients awaiting HPCT. Prior to transplantation, clinical exploration and
      radiology were carried out and oral photographs were taken. This evaluated the
      extent of caries present, the number of missing teeth and the number of dental
      fillings in each patient; CAO (Caries and Obturations Index) DMFS (Decayed,
      Missing, and Filled Surfaces) and Restoration Indices were calculated. Gingival
      pathology was also examined by means of the Ainamo and Bay Gingival Bleeding
      Index. O'Leary's Plaque Index was used to evaluate the level of patient oral
      hygiene. This data was analyzed to see if it exercised any influence on the
      mucositis grade suffered during HPCT. RESULTS: 96,87% of patients suffered some
      degree of mucositis during their treatment by the Transplant Unit. The grade of
      mucositis was seen to be influenced by the number of missing teeth (ANOVA
      p<0.016) and by the DMFS Index (ANOVA p< 0.038). Although this was not one of the
      aims of this study, patient age and the administration of colony-stimulating
      factors were also seen to influence these clinical manifestations. CONCLUSIONS:
      The state of prior oral health can influence decisively the mucositis suffered
      during transplantation.

PMID- 22157661
TI  - Influence of the patients' sex, type of dental prosthesis and antagonist on
      residual bone resorption at the level of the premaxilla.
AB  - OBJECTIVES: To analyze the height and width of the ridge at the level of the
      premaxilla in edentulous patients, evaluating whether the sex of the patient,
      type of prosthetic rehabilitation and antagonist have an influence. MATERIAL AND
      METHOD: We randomly selected a total of 89 patients, having an average age of
      66.21 years old. A total of 308 measurements were made, all of them at the level
      of the premaxilla, in the intercanine area. As dependent variables, we analyzed
      the patients' sex, age and the antagonist: removable (dental) prostheses (RP),
      fixed (dental) prostheses (FD), natural dentition (ND). As independent variables,
      we measured the height and residual width in sagittal sections provided by
      tomographic studies using Dentascan(r). RESULTS: We observed a significantly
      smaller ridge in women versus in men, and in patients whose antagonist was a
      fixed prosthesis; whereas for the type of prosthesis, we did not observe
      significant differences between the two categories analyzed. CONCLUSIONS: Bone
      resorption at the level of the premaxilla is a variable process in which a
      smaller size is observed (height and width) in women and when the antagonist is a
      fixed prosthesis.

PMID- 22157662
TI  - Central odontogenic fibroma: retrospective study of 8 clinical cases.
AB  - INTRODUCTION AND OBJECTIVES: The central odontogenic fibroma (COF) is a benign
      odontogenic tumour derived from the dental mesenchymal tissues. It is a rare
      tumour and only 70 cases of it have been published. Bearing in mind the rareness
      of the tumour, 8 new cases of central odontogenic fibroma have been found by
      analyzing the clinical, radiological and histopathological characteristics of
      COF. PATIENTS AND METHOD: A retrospective study was carried out on 3011 biopsies
      in the Service of Oral and Maxillofacial Surgery of the Dental Clinic of
      Barcelona University between January 1995 and March 2008. 85 odontogenic tumours
      were diagnosed of which 8 were central odontogenic fibroma. The radiological
      study was based on orthopantomographs, periapical and occlusal radiographies and
      computerised tomographics. The variables collected were: sex, age, clinical
      characteristics of the lesion, treatment received and possible reappearances of
      the tumour. RESULTS: The central odontogenic fibroma represents 9.4% of all
      odontogenic tumours. Of the 8 cases, 5 were diagnosed in men and 3 in women. The
      average age was 19.9 years with an age range of 11 to 38 years. The most common
      location of the tumour was in the mandible. All cases were associated with
      unerupted teeth. Of the 8 tumours, 3 provoked rhizolysis of the adjacent teeth
      and 4 cases caused cortical bone expansion. 50% of the patients complained of
      pain associated to the lesion. No case of recurrence was recorded up to 2 years
      after the treatment. CONCLUSIONS: Central odontogenic fibromas usually evolve
      asymptomatically although they can manifest very aggressively provoking dental
      displacement and rhizolysis. Radiologically, COF manifest as a uni or
      multilocular radiotransparent image although they can be indistinguishable from
      other radiotransparent lesions making diagnosis more difficult. COF treatment
      involves conservative surgery as well as follow-up patient checks.

PMID- 22157663
TI  - Virtual articulator for the analysis of dental occlusion: an update.
AB  - The future of dental practice is closely linked to the utilization of computer
      based technology, specifically virtual reality, which allows the dental surgeon
      to simulate true life situations in patients. The virtual articulator has been
      designed for the exhaustive analysis of static and dynamic occlusion, with the
      purpose of substituting mechanical articulators and avoiding their errors. These
      tools will help both odontologists and dental prosthetists to provide the best
      individualized treatment for each patient. The present review analyzes the
      studies published in the literature on the design, functioning and applications
      of virtual articulators. A Medline-PubMed search was made of dental journals,
      with the identification of 137 articles, of which 16 were finally selected. The
      virtual articulator can simulate the specific masticatory movement of the
      patient. During mandibular animation, the program calculates the sites where the
      opposing teeth come into contact. The studies made to assess the reliability of
      the virtual articulator show good correspondence in visualization of the number
      and position of the dynamic contacts. The virtual articulator is a precise tool
      for the full analysis of occlusion in a real patient.

PMID- 22157664
TI  - Articaine versus lidocaine for third molar surgery: a randomized clinical study.
AB  - OBJECTIVE: Pain reduction has been the subject of continuous research in the
      field of oral and maxillofacial surgery since postoperative pain with ranging of
      intensity and duration may affects the patient submitted in an oral surgical
      procedure. The aim of present study was to compare the analgesic effectiveness
      between two different anesthetic solutions (articaine and lidocaine) in third
      molar surgery. STUDY DESIGN: A prospective, randomized and clinical study with
      patients submitted to third molar surgery at two distinct times. The visual
      analogue scale, the McGill Pain Questionnaire and the analgesic consumption
      record were used to measure the pain after each surgical time. RESULTS: Duration
      of surgery, latency, the amount of anesthetic used and analgesic consumption
      showed clinical differences with highlights of articaine, though statistical
      significance was not observed (P<0.05). The pain scores indicated similar
      anesthetic efficacy with both solutions. CONCLUSION: In the present study no
      significant differences were observed between lidocaine and articaine in the
      control of postoperative pain.

PMID- 22157665
TI  - Increased TNF-alpha, IL-6 and decreased IL-1beta immunohistochemical expression
      by the stromal spindle-shaped cells in the central giant cell granuloma of the
      jaws.
AB  - OBJECTIVES: the expression of the osteoclastogenic cytokines TNF-alpha, IL-6 and
      IL-1beta were immunohistochemically evaluated in peripheral (PGCG) and central
      (CGCG) giant cell granulomas of the jaws in order to determine differences
      between these two lesions and between the two distinct tumor cell populations
      (multinucleated giant cells, MGCs and stromal spindle-shaped cells). STUDY
      DESIGN: Paraffin-embedded tissue sections from 40 PGCG and 40 CGCG were
      immunohistochemically stained using antibodies against TNF-alpha, IL-6 and IL
      1beta. The percentage of positively stained cells and the staining intensity were
      assessed to provide a combined immunoreactivity score value. RESULTS: TNF-alpha,
      IL-6 and IL-1beta were expressed in all lesions. The CGCG compared to the PGCG
      showed significantly increased expression of TNF-alpha and IL-6 and decreased
      expression of IL-1beta by the spindle-shaped cells and increased expression of IL
      1beta by the MGCs. The MGCs demonstrated in comparison to the stromal spindle
      shaped cells significantly increased expression of all three cytokines in both
      PGCG and CGCG. CONCLUSIONS: The proinflammatory cytokines TNF-alpha, IL-6 and IL
      1beta seem to be involved in the growth process of PGCG and CGCG of the jaws. A
      possible alteration in the synthesis or/and activity of these cytokines by the
      stromal spindle cells in the CGCGs may enhance osteolysis through the stimulation
      of osteoclast progenitor cells, given the fact that the intraosseous lesions
      cause bone resorption.

PMID- 22157666
TI  - Study of total stimulated saliva flow and hyperpigmentation in the oral mucosa of
      patients diagnosed with hereditary hemochromatosis. Series of 25 cases.
AB  - OBJECTIVE: To study lesions in the oral cavity of patients with hereditary
      hemochromatosis and determine their association with iron overload. STUDY DESIGN:
      We took a clinical history, examined the pigmentation of the oral mucosa, and
      measured total stimulated saliva production. We correlated our results with
      epidemiological, phenotypic, and genotypic findings. Patients with associated
      diseases or drug therapy causing xerostomia were excluded. RESULTS: We evaluated
      25 patients (20 men, mean age 52 years) over a period of 6 months. No patient
      complained of xerostomia and pigmentation was not detected in the oral mucosa.
      The total stimulated salivary flow was reduced in 9 patients who had an average
      ferritin level of 796.5 ug/l. The decline in total stimulated salivary flow was
      significantly correlated with ferritin levels (p=0.002). Patients with ferritin
      levels within the normal range also had normal stimulated salivary flow.
      CONCLUSIONS: We found no pigmented lesions in the oral mucosa; however, we did
      observe a decrease in total stimulated salivary flow that correlated with
      ferritin levels. Therefore, hyposialia caused by functional impairment of the
      salivary glands may be an early marker of iron deposition.

PMID- 22157668
TI  - Bacteremia following dental implant surgery: preliminary results.
AB  - OBJECTIVES: The aims of this study were to investigate the incidence of
      bacteremia, bacteriology and antibiotic susceptibility against to causative
      bacteria associated with dental implant installation. STUDY DESIGN: 30 generally
      healthy patients were enrolled in this study. Blood samples were collected at
      baseline and at 30 minutes after dental implant installation and 24 hours after
      dental implant surgery. Blood samples were cultured in a BACTEC system. The
      isolated bacteria were identified using conventional methods. Antimicrobial
      sensitivity tests were performed by disc diffusion. RESULTS: No bacteria were
      isolated at the baseline and 24 hours after surgery, whereas the prevalence of
      bacteremia at 30 minutes after dental implant installation was 23%. The isolated
      bacteria species were Staphylococcus epidermidis, Eubacterium spp.,
      Corynebacterium spp. and Streptococcus viridans. The Staphylococcus epidermidis,
      which was isolated in three patients, was found to be resistant to penicillin
      which is first choice of many clinicians. CONCLUSION: Our findings suggest that
      installation of dental implants can produce bacteremia. Within the limitations of
      this study, it can be speculated that the resistance of antibiotics may
      compromise the routine prophylaxis against infective endocarditis. Therefore use
      of blood cultures and antibiograms may be suggested in risky patients. The
      outcome of the present study should be verified using a larger patient group with
      varying conditions.

PMID- 22157667
TI  - Expression of the gene encoding secretor type galactoside 2 alpha
      fucosyltransferase (FUT2) and ABH antigens in patients with oral lesions.
AB  - OBJECTIVE: The aim of this work was to evaluate the expression of FUT2 gene in
      saliva and histo ABH antigens of patients with oral lesions. STUDY DESIGN: In
      total 178 subjects were examined, half of whom suffered from oral pre-cancerous
      and cancerous lesions, while the other half were the healthy control group We
      analyzed the FUT 2 polymorphism by ASO-PCR (allele specific oligonucleotid -
      polymerase chain reaction) with specific primers for G428 allele and the wild
      type allele of FUT2 gene. To reveal A, B and H antigens in tissue sections of the
      patients (n= 89) we used a modified specific red cell adherence technique.
      RESULTS: We found a high intensity of oral disease in the non-secretor group (OR
      = 2.43). A total of 58% of the patients with oral pre-cancerous and cancerous
      lesions was non secretors (se_/_), in contrast with the healthy population
      (21.5%). A strongly positive reaction was defined as a sheet of indicator
      erythrocytes adhered to the epithelial cells. In 31 of the 54 samples analyzed
      the test showed slightly positive results on atypical areas, and there was a
      complete antigen deletion in areas affected by neoplasia. Nineteen samples showed
      a total absence of ABH antigens in both histologically normal and pathological
      areas. Blood group antigens were expressed at a high level in benign and highly
      differentiated malignant tumors. In poorly differentiated malignant tumors, they
      were mostly absent. CONCLUSION: Considering these results we suggest the use of
      this method to monitor probable preneoplastic lesions in risk population,
      especially in those with no secretor status (absence of FUT2 gene).

PMID- 22157669
TI  - Suture needles in oral surgery: alterations depending on the type and number of
      sutures.
AB  - This study examined whether the number and type of sutures used in oral surgery
      influence two ad hoc variables (incision plane and displaced area), which are two
      variables related to whether the suture needle is suitable for the task. Seventy
      five TB-15 needles were studied, which were used to suture between zero and three
      mucosa and/subperiosteal sutures, producing 15 groups with 5 needles in each one.
      The incision plane and displaced area were measured for each group, which are two
      variables related to how the needle has worn and altered. Statistical treatment
      was conducted using the Kruskal-Wallis H test to compare multiple values and the
      Mann-Whitney U test to compare pairs. A multi-stage regression model was applied
      with the aim of predicting the changes in the dependent variables based on the
      number and type of sutures performed. The incision plane ranged from 126.67 to
      346.24 um among the different groups. The displaced area was measured as being
      between 14 524.83 um2 and 128 311.91 um2. The best predictive model for the
      incision plane obtained a coefficient of determination (R2) of 0.149, while it
      reached 0.249 for the displaced area. Subperiosteal sutures held more weighting
      among the variables studied. Mucosal sutures did not seem to greatly affect
      needle wear. Observations reported in this paper indicate that the needle should
      be changed after having performed two subperiosteal sutures, given the wear and
      change to the incision plane that is produced, which causes the needle's cutting
      ability to reduce.

PMID- 22157670
TI  - Transcrestal sinus lift and implant placement  using the sinus balloon technique.
AB  - OBJECTIVE: A description is made of transcrestal sinus lift using the sinus
      balloon technique, evaluating the bone height achieved and implant success one
      year after prosthetic loading. MATERIAL AND METHOD: Between January and July
      2007, transcrestal sinus lift using the sinus balloon technique for dental
      implant placement was carried out in 6 patients. A panoramic X-ray study and
      maxillary computed tomography scan were carried out before the operation, in
      order to discard possible sinus pathology. During the intervention, the integrity
      of the sinus membrane was evaluated using a Medi Pack Pal endoscope (Farol Store
      and Co., Tuttlingen, Germany), and the intraoperative complications were
      analyzed. The dental implants were placed in the same surgical step in the
      presence of 3 mm or more of residual bone. Following the operation, panoramic X
      rays were used to assess the bone height gained. One year after prosthetic
      loading, the implant success rate was determined based on the criteria of Buser.
      RESULTS: One patient was excluded due to Schneider's membrane perforation as
      confirmed by endoscopy. Transcrestal sinus lift was carried out in 5 males with a
      mean age of 41.6 years (range 27-51), without antecedents of sinus disease. There
      were no intraoperative complications. In four patients the implants were placed
      simultaneous to sinus lift, while in another case implant placement was postponed
      due to insufficient remaining bone height. The mean gain in height after the
      operation was 8.7 mm. One year after prosthetic loading, the implant success rate
      was 100%. CONCLUSIONS: Transcrestal sinus lift using the sinus balloon technique
      is a minimally invasive procedure. In 5 patients the bone height gained proved
      sufficient to allow implant placement even in the presence of 3 mm of residual
      bone.

PMID- 22157671
TI  - Comparison of two histopathologic methods for evaluating  subcutaneous reaction
      to mineral trioxide aggregate.
AB  - OBJECTIVES: One of the most important factors for suitable materials for pulp
      therapy is biocompatibility. Two histopathologic methods of Cox and Federation
      Dentaire International (FDI) were used to evaluate inflammation. In Cox method,
      density of inflammatory cells, tissue reactions like fibrosis, vascular responses
      like congestion and fibrin extravasation have been used to evaluate inflammatory
      reactions. The aim of this study was to compare the accuracy of pathologists'
      interpretations using two different methods. STUDY DESIGN: Three pathologists
      observed the degree of inflammation in 225 histopathologic sections. These
      sections showed inflammation in subcutaneous connective tissue of rats adjacent
      to polyethylene tubes, filled with white or gray mineral trioxide aggregate.
      Empty tubes served as controls. Samples were harvested after 7-, 15-, 30-, 60-,
      and 90-days. All pathologists examined the sections under a light microscope
      (Carl Zeiss, Oberkochen, Germany) at *400 magnifications. Chi-Square test was
      used to evaluate the difference between inflammation grades when one pathologist
      used two methods. Cohen's Kappa value was used to measure agreement of three
      pathologists to recognize the degrees of inflammations when using one of the
      methods. RESULTS: There were no significant differences between the two methods
      when one of the pathologist used these methods to report the degree of
      inflammation (p=0.054). However, two other pathologists reported significant
      differences between two methods (p=0.005, p=0.001). In the FDI method, there was
      an acceptable agreement between first and second, and first and third pathologist
      in terms of the degree of inflammation, and intermediate agreement existed
      between the second and third pathologist. With the Cox method, no agreement among
      the pathologists could be found. CONCLUSION: The results of three pathologists in
      terms of rating inflammation with the FDI method showed better agreement than
      with the Cox method. Therefore, FDI method is more reliable than the Cox method
      to evaluate inflammation.

PMID- 22157672
TI  - Prevalence of systemic diseases among patients requesting dental  consultation in
      the public and private systems.
AB  - OBJECTIVES: To determine the prevalence and aetiology of systemic disease among
      patients requesting dental treatment in public and private practice. STUDY
      DESIGN: A retrospective analysis was performed of the medical histories of 2000
      patients requesting dental treatment during the year 2009. One thousand patients
      came from the Fontinas Primary Care Oral and Dental Health Unit of the Galician
      Health Service (SERGAS), Spain, and the other thousand from a private clinic;
      both clinics were situated in Santiago de Compostela, La Coruna, Spain. The data
      collected were the following: demographic data (age and sex), presence or absence
      of systemic diseases and the nosologic categories, and drug history (type and
      number of drugs). RESULTS: The prevalence of systemic disease was significantly
      higher among patients seen in the public system (35.2% in the public system
      versus 28.1% in the private system; p= 0.003). The differences between the two
      systems were more marked when considering patients aged under 65 years,
      particularly with respect to rheumatic and endocrine-metabolic (diabetes)
      disorders. The prevalence of patients receiving polypharmacy (>4 drugs/day) was
      significantly higher among patients seen in the public system (5.7% in the public
      system versus 2.7% in the private system; p= 0.009). CONCLUSIONS: There is a high
      prevalence of medical disorders and of patients receiving polypharmacy among
      individuals requesting dental care, particularly in the public health system.
      Dentists must have adequate training in medical disease and must be fully
      integrated into primary care health teams in order to prevent or adequately
      resolve complications.

PMID- 22157673
TI  - Double-application of platelet-rich plasma on bone healing in rabbits.
AB  - OBJECTIVE: Platelet-rich plasma (PRP) is considered to enhance bone formation
      especially at early stages of wound healing, depending on the limited and short
      life-span of platelets and growth factors. The aim of this study was to evaluate
      efficacy of double-application of PRP (DA-PRP) on bone healing in a rabbit
      calvarial defect model. STUDY DESIGN: Twenty-eight rabbits, each had two
      surgically prepared calvarial bone defects (10mm diameter), were included in this
      study and randomly divided into six groups. Defects (n=56) were treated with
      single-application of PRP (SA-PRP)(n=10), SA-PRP and beta-tricalciumphosphate (SA
      PRP+TCP)(n=10), DA-PRP (n=8), DA-PRP and beta-tricalciumphosphate (DA
      PRP+TCP)(n=8), beta-tricalciumphosphate (TCP)(n=10) or left empty
      (Control)(n=10). Animals were sacrificed at 30 days postoperatively. RESULTS: The
      new bone (NB%) and defect fill (DF%) percentages were calculated from
      histological slides by image-analyzer software and statistically analysed. All
      test groups showed higher NB% than control, but differences among all groups were
      insignificant. The TCP treated groups had significantly higher DF% than groups
      treated without TCP, however the DF% differences between control, SA-PRP and DA
      PRP or TCP, SA-PRP+TCP or DA-PRP+TCP were insignificant. CONCLUSION: Although new
      bone formation was histomorphologically remarkable at double-application PRP
      groups, statistical analyses of the histomorphometric data revealed no
      significant difference.

PMID- 22157674
TI  - Histopathology of ameloblastoma of the jaws; some critical observations based on
      a 40 years single institution experience.
AB  - The aim of the present study is to examine all cases of intraosseous benign
      ameloblastomas treated between 1970 and 2010 in a single institution and to look
      for a possible correlation between the histopathological aspects and the
      demographical and clinical parameters, as well as the treatment outcome. The data
      of a total number of 44 patients were retrieved from the records. Nine patients
      were excluded because of doubt about the correct diagnosis (8 patients) or
      because of an extra-osseous presentation (1 patient).  No statistically
      significant differences were found between the histopathological (sub)types of
      ameloblastomas and the demographical and clinical parameters, nor between the
      histopathological (sub)types and treatment outcome. Of the 28 patients treated by
      enucleation, in 17 patients one or more recurrences occurred, with no significant
      predilection for any histopathological (sub)type, including the unicystic type.
      There were no significant differences in the recurrence rate after enucleation in
      patients below and above the age of 20 years either. In six out of 17 patients
      with a recurrence, the recurrent lesion showed a different histopathological
      subtype than was encountered in the primary. In two cases a change from
      solid/multicystic to desmoplastic ameloblastomas was noticed.  In conclusion, the
      current histopathological classification of benign intraosseous ameloblastoma
      does not seem to have clinical relevance with the possible exception of the
      luminal unicystic ameloblastoma that has been removed in toto, unfragmented.
      Since no primary desmoplastic ameloblastomas were encountered in the present
      study no further comments can be made on this apparently rare entity.

PMID- 22157675
TI  - Interplay between action and movement intentions during social interaction.
AB  - Observing the movements of another person influences the observer's intention to
      execute similar movements. However, little is known about how action intentions
      formed prior to movement planning influence this effect. In the experiment
      reported here, we manipulated the congruency of movement intentions and action
      intentions in a pair of jointly acting individuals (i.e., a participant paired
      with a confederate coactor) and investigated how congruency influenced
      performance. Overall, participants initiated actions faster when they had the
      same action intention as the coactor (i.e., when participants and the coactor
      were pursuing the same conceptual goal). Participants' responses were also faster
      when their and the coactor's movement intentions were directed to the same
      spatial location, but only when participants had the same action intention as the
      coactor. These findings suggest that observers use the same representation to
      implement their own action intentions that they use to infer other people's
      action intentions and also that a dynamic, multitiered intentional mechanism is
      involved in the processing of other people's actions.

PMID- 22157676
TI  - Progressive taxation and the subjective well-being of nations.
AB  - Using data from the Gallup World Poll, we examined whether progressive taxation
      is associated with increased levels of subjective well-being. Consistent with
      Rawls's theory of justice, our results showed that progressive taxation was
      positively associated with the subjective well-being of nations. However, the
      overall tax rate and government spending were not associated with the subjective
      well-being of nations. Furthermore, controlling for the wealth of nations and
      income inequality, we found that respondents living in a nation with more
      progressive taxation evaluated their lives as closer to the best possible life
      and reported having more positive and less negative daily experiences than did
      respondents living in a nation with less-progressive taxation. Finally, we found
      that the association between more-progressive taxation and higher levels of
      subjective well-being was mediated by citizens' satisfaction with public goods,
      such as education and public transportation.

PMID- 22157677
TI  - The group-member mind trade-off: attributing mind to groups versus group members.
AB  - People attribute minds to other individuals and make inferences about those
      individuals' mental states to explain and predict their behavior. Little is
      known, however, about whether people also attribute minds to groups and believe
      that collectives, companies, and corporations can think, have intentions, and
      make plans. Even less is known about the consequences of these attributions for
      both groups and group members. We investigated the attribution of mind and
      responsibility to groups and group members, and we demonstrated that people make
      a trade-off: The more a group is attributed a group mind, the less members of
      that group are attributed individual minds. Groups that are judged to have more
      group mind are also judged to be more cohesive and responsible for their
      collective actions. These findings have important implications for how people
      perceive the minds of groups and group members, and for how attributions of mind
      influence attributions of responsibility to groups and group members.

PMID- 22157678
TI  - Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory
      signaling.
AB  - Exuberant fibroproliferation is a common complication after injury for reasons
      that are not well understood. One key component of wound repair that is often
      overlooked is mechanical force, which regulates cell-matrix interactions through
      intracellular focal adhesion components, including focal adhesion kinase (FAK).
      Here we report that FAK is activated after cutaneous injury and that this process
      is potentiated by mechanical loading. Fibroblast-specific FAK knockout mice have
      substantially less inflammation and fibrosis than control mice in a model of
      hypertrophic scar formation. We show that FAK acts through extracellular-related
      kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant
      protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human
      fibrotic disorders. Similarly, MCP-1 knockout mice form minimal scars, indicating
      that inflammatory chemokine pathways are a major mechanism by which FAK
      mechanotransduction induces fibrosis. Small-molecule inhibition of FAK blocks
      these effects in human cells and reduces scar formation in vivo through
      attenuated MCP-1 signaling and inflammatory cell recruitment. These findings
      collectively indicate that physical force regulates fibrosis through inflammatory
      FAK-ERK-MCP-1 pathways and that molecular strategies targeting FAK can
      effectively uncouple mechanical force from pathologic scar formation.

PMID- 22157679
TI  - Reciprocal repression between P53 and TCTP.
AB  - Screening for genes that reprogram cancer cells for the tumor reversion switch
      identified TCTP (encoding translationally controlled tumor protein) as a crucial
      regulator of apoptosis. Here we report a negative feedback loop between P53 and
      TCTP. TCTP promotes P53 degradation by competing with NUMB for binding to P53
      MDM2-containing complexes. TCTP inhibits MDM2 auto-ubiquitination and promotes
      MDM2-mediated ubiquitination and degradation of P53. Notably, Tctp
      haploinsufficient mice are sensitized to P53-dependent apoptosis. In addition,
      P53 directly represses TCTP transcription. In 508 breast cancers, high-TCTP
      status associates with poorly differentiated, aggressive G3-grade tumors,
      predicting poor prognosis (P < 0.0005). Tctp knockdown in primary mammary tumor
      cells from ErbB2 transgenic mice results in increased P53 expression and a
      decreased number of stem-like cancer cells. The pharmacological compounds
      sertraline and thioridazine increase the amount of P53 by neutralizing TCTP's
      action on the MDM2-P53 axis. This study links TCTP and P53 in a previously
      unidentified regulatory circuitry that may underlie the relevance of TCTP in
      cancer.

PMID- 22157680
TI  - Successful prenatal mannose treatment for congenital disorder of glycosylation-Ia
      in mice.
AB  - Congenital disorder of glycosylation-Ia (CDG-Ia, also known as PMM2-CDG) is
      caused by mutations in the gene that encodes phosphomannomutase 2 (PMM2, EC
      5.4.2.8) leading to a multisystemic disease with severe psychomotor and mental
      retardation. In a hypomorphic Pmm2 mouse model, we were able to overcome
      embryonic lethality by feeding mannose to pregnant dams. The results underline
      the essential role of glycosylation in embryonic development and may open new
      treatment options for this disease.

PMID- 22157681
TI  - EGFR and MET receptor tyrosine kinase-altered microRNA expression induces
      tumorigenesis and gefitinib resistance in lung cancers.
AB  - The involvement of the MET oncogene in de novo and acquired resistance of non
      small cell lung cancers (NSCLCs) to tyrosine kinase inhibitors (TKIs) has
      previously been reported, but the precise mechanism by which MET overexpression
      contributes to TKI-resistant NSCLC remains unclear. MicroRNAs (miRNAs) negatively
      regulate gene expression, and their dysregulation has been implicated in
      tumorigenesis. To understand their role in TKI-resistant NSCLCs, we examined
      changes in miRNA that are mediated by tyrosine kinase receptors. Here we report
      that miR-30b, miR-30c, miR-221 and miR-222 are modulated by both epidermal growth
      factor (EGF) and MET receptors, whereas miR-103 and miR-203 are controlled only
      by MET. We showed that these miRNAs have important roles in gefitinib-induced
      apoptosis and epithelial-mesenchymal transition of NSCLC cells in vitro and in
      vivo by inhibiting the expression of the genes encoding BCL2-like 11 (BIM),
      apoptotic peptidase activating factor 1 (APAF-1), protein kinase C E (PKC-E) and
      sarcoma viral oncogene homolog (SRC). These findings suggest that modulation of
      specific miRNAs may provide a therapeutic approach for the treatment of NSCLCs.

PMID- 22157682
TI  - Cardiometabolic benefits of exercise training in an experimental model of
      metabolic syndrome and menopause.
AB  - OBJECTIVE: The aim of this study was to investigate the cardiometabolic effects
      of exercise training in ovariectomized hypertensive rats both submitted and not
      submitted to fructose overload. METHODS: Spontaneously hypertensive
      ovariectomized rats were divided into sedentary and trained (THO) groups
      submitted to normal chow and sedentary and trained groups submitted to fructose
      overload (100 g/L in drinking water for 19 wk). Exercise training was performed
      on a treadmill (8 wk). Arterial pressure (AP) was directly recorded.
      Cardiovascular autonomic control was evaluated through pharmacological blockade
      (atropine and propranolol) and in the time and frequency domains by spectral
      analysis. RESULTS: The THO group presented reduced AP (approximately 16 mm Hg)
      and enhanced cardiac vagal tonus (approximately 49%) and baroreflex sensitivity
      (approximately 43%) compared with the sedentary hypertensive ovariectomized
      group. Exercise training attenuated metabolic impairment, resting tachycardia,
      cardiac and vascular sympathetic increases, and baroreflex sensitivity decrease
      induced by fructose overload in hypertensive rats. However, the trained
      hypertensive ovariectomized group submitted to fructose overload presented higher
      AP (approximately 32 mm Hg), associated with baroreflex sensitivity
      (approximately 69%) and parasympathetic dysfunctions compared with the THO group.
      CONCLUSIONS: These data suggest that the metabolic disorders in hypertensive rats
      after ovarian hormone deprivation could blunt and/or attenuate some exercise
      training benefits.

PMID- 22157683
TI  - Is functional capacity related to the daily amount of steps in postmenopausal
      women?
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between
      functional capacity, muscle function, and daily step count in postmenopausal
      women. METHODS: Fifty-seven postmenopausal women aged 50 to 70 years were
      recruited. Body composition (body weight, body mass index, fat mass, and skeletal
      muscle mass), energetic metabolism (maximal oxygen consumption, total energy
      expenditure, daily step count), and functional capacity (muscle strength, muscle
      quality, chair stand, balance and alternate step tests) were measured. Women were
      divided into three groups (sedentary [n = 19], <7,500 steps; moderately active [n
      = 20], 7,500-10,000 steps; active [n = 18], >10,000 steps). RESULTS: A higher
      number of steps per day was associated with higher maximal oxygen consumption
      (mL/min per kg; P = 0.001) and total energy expenditure (P = 0.004) as well as
      lower body weight (P = 0.035) and fat mass (P = 0.048). Surprisingly, no
      differences for skeletal muscle mass, muscle strength, muscle quality, and
      functional capacity were observed between the groups, although this could have
      been because of the small sample size. CONCLUSIONS: A daily amount of 10,000
      steps seems to be associated with better body composition and higher
      cardiovascular functions. However, neither functional capacity nor muscle
      functions seem to be related to the daily amount of steps in postmenopausal
      women. Further prospective studies are needed to confirm our preliminary results
      because cross-sectional study designs do not permit the understanding of temporal
      relations.

PMID- 22157684
TI  - Evaluation of the spinal pain score in AS--a psychometric analysis.
AB  - OBJECTIVE: To evaluate the spinal pain score (SpiPS), a semi-objective instrument
      for measuring disease activity in AS. METHODS: The SpiPS is based on the physical
      examination of the spine and was evaluated according to the outcome measures in
      rheumatology filter in 659 AS patients from different cohorts including two
      interventional trials. Aspects of truth, discrimination and feasibility were
      assessed. RESULTS: The SpiPS significantly distinguished between patients with
      high and low disease activity. The correlation of the SpiPS with the disease
      activity index BASDAI was relatively weak in the entire cohort of AS patients (r
      = 0.36) but moderate to good in AS patients with short disease duration (r =
      0.66). Correlations with the functional index BASFI (r = 0.38), patient global (r
      = 0.18), physician global (r = 0.51) and BASMI (r = 0.36) were weak to moderate
      in the entire cohort. Logistic regression revealed SpiPS and patient global to be
      independently associated with disease activity (BASDAI) after adjustments for
      age, gender, disease duration, CRP and HLA-B27. Sensitivity to change expressed
      as effect size (ES) was 0.82 and 1.58, respectively, and highly comparable with
      that of BASDAI in the two interventional trials. Reproducibility of the SpiPS was
      good (intra-observer variability r = 0.93, inter-observer variability r = 0.79).
      CONCLUSION: The SpiPS is a measure of disease activity in AS and is sensitive to
      change. However, disease domains other than disease activity are also captured by
      the SpiPS, and our analysis failed to demonstrate any additional value of the
      SpiPS over existing instruments.

PMID- 22157685
TI  - Antibodies to common infectious agents in coronary artery disease patients with
      and without rheumatic conditions.
AB  - OBJECTIVES: The mechanism linking inflammation to atherosclerosis is unknown. We
      have previously demonstrated a high occurrence of inflammation in the aortic
      adventitia of patients with coronary artery disease (CAD), which was more
      pronounced in patients with inflammatory rheumatic diseases (IRDs), and which
      might be involved in the pathogenesis of cardiovascular disease. In theory,
      infections might play a role in the pathogenesis of vascular inflammation or
      atherosclerosis, or both. This study compared seropositivity and the burden of
      several common infections in patients with CAD, both with and without IRD, and in
      healthy controls (HCs). Moreover, we looked for relationships between the
      examined antibodies and inflammatory infiltrates in the aortic adventitia.
      METHODS: We examined sera for Chlamydophila pneumoniae, Mycoplasma pneumoniae,
      Helicobacter pylori, CMV, Streptococcus pyogenes, parvovirus B19, HBV and HCV
      with commercially available serological tests in 67 patients with IRD, 52
      patients without IRD and 30 HCs. RESULTS: We observed neither any statistically
      significant differences in the examined antibodies between the groups nor a
      difference in the burden of infection. Except for a protective effect of
      mycoplasma immunoglobulin A (IgA), we did not find any other associations between
      the examined antibodies and the occurrence of aortic adventitial mononuclear cell
      infiltrates. CONCLUSION: Our study does not support the notion that chronic
      infections or infectious burden contribute to accelerated occurrence of CAD in
      IRD. Mycoplasma IgA was related to a lower occurrence of aortic adventitial
      inflammation.

PMID- 22157686
TI  - Prophylactic human papillomavirus vaccines:  past, present and future.
AB  - Human papillomavirus (HPV) is a highly transmissible infection responsible for a
      range of diseases in women including cervical carcinomas, vulval carcinomas,
      anogenital carcinomas and genital warts. In men it is associated with penile
      carcinomas, anogenital carcinomas and oropharyngeal carcinomas. The history of
      the development of HPV vaccines includes a significant Australian input and
      represents a tremendous advancement in our understanding of HPV virology as well
      as further elucidating the overall contribution of viruses to carcinogenesis.
      Prophylactic HPV vaccines were licensed for use in Australia in 2007 in order to
      protect against development of future cases of cervical carcinoma and early
      results are promising. The benefit of the vaccine will not be restricted to
      cervical lesions and cross protection amongst a variety of HPV subtypes is
      described. The development of the HPV vaccine and its ultimate incorporation into
      our National Immunisation Schedule is reviewed.

PMID- 22157687
TI  - Filiform serrated adenoma is an unusual, less aggressive variant of traditional
      serrated adenoma.
AB  - AIMS: Filiform serrated adenoma (SA) is an uncommon type of polyp that shows
      morphological features similar to traditional serrated adenoma (TSA). Unlike TSA,
      filiform SA is composed predominantly of prominent, thin, elongated filiform
      projections lined by neoplastic epithelium with a serrated contour. However, the
      molecular pathogenesis underlying filiform SA is unclear and its relationship
      with TSA has not been explored yet. The purpose of this study was to determine
      the clinicopathological and molecular characteristics of filiform SA in a cohort
      of Korean patients. METHODS: Thirteen filiform SAs were evaluated for mutations
      of BRAF and KRAS genes, microsatellite instability (MSI), and promoter
      hypermethylation of hMLH1, MGMT, p16, MINT1, MINT2, MINT31 and the APC genes. The
      clinicopathological and molecular results were compared to results from
      previously published studies of left-sided TSAs among Koreans. RESULTS: All but
      one filiform SAs were located in the left colon and showed low grade dysplasia.
      BRAF and KRAS mutations were observed in six (46.2%) and four (30.3%) filiform
      SAs, respectively. Hypermethylation of hMLH1 (using both Herman et al. and Park
      et al.), MGMT, p16, MINT1, MINT2, MINT31 and the APC gene was found in 30.3% and
      7.7%, 38.5%, 15.4%, 53.8%, 46.2%, 38.5% and 15.4% of cases, respectively.
      Thirteen filiform SAs were MS stable and classified with a CpG island methylator
      phenotype (CIMP) of high in five, CIMP low in five and CIMP negative in three
      cases. Compared to TSAs in the left colon, methylation of hMLH1, APC, and MGMT
      was less frequent in cases of filiform SA, but the filiform SA sizes were larger.
      CONCLUSION: Our findings suggest that filiform SA may grow larger without
      acquisition of additional genetic alterations and can be categorised as a rare,
      less aggressive variant of TSA with unique morphology.

PMID- 22157688
TI  - The utility and limitation of single nucleotide polymorphism analysis on whole
      genome amplified mesenchymal tumour DNA in formalin fixed tumour samples.
AB  - AIMS: In the study of tumour genetics, formalin fixed, paraffin embedded (FFPE)
      tumours are the most readily available tissue samples and DNA derived from FFPE
      tissue has been validated for array comparative genomic hybridisation (aCGH) and
      single nucleotide polymorphism (SNP) array analysis. Furthermore, in the study of
      tumour precursor genetics, whole genome amplification (WGA) has been used to
      produce a sufficient amount of DNA for aCGH. However, it is unclear whether the
      same approach can be extended to high-resolution SNP analysis. METHODS: In this
      study, we examined the utility and limitations of genotyping platforms performed
      on WGA DNA from FFPE mesenchymal tumour samples for both copy number and SNP
      analyses. We analysed the results obtained using DNA derived from matched FFPE
      and frozen tissue samples on the Affymetrix 250K Nsp SNP array. Two widely used
      WGA methods, Qiagen (isothermal protocol) and Sigma (thermocycling protocol) were
      employed to determine how WGA methods affect the results. RESULTS: We found that
      the use of WGA DNA derived from FFPE mesenchymal tumours for high-resolution SNP
      array application can produce a significant amount of false positive and false
      negative findings. While some of these misinterpretations appear to cluster in
      genomic regions with high or low GC contents, the majority appears to occur
      randomly. Only large scale chromosome loss of heterozygosity (LOH) (>10 Mb) can
      be reliably detected from WGA FFPE tumour DNA samples but not smaller LOH or copy
      number alterations. CONCLUSIONS: Our findings here indicate a need for caution in
      SNP array data interpretation when using WGA FFPE tumour-derived DNA in
      determining genomic alterations less than 10 Mb.

PMID- 22157689
TI  - A case of carbapenemase-producing Klebsiella pneumoniae in Australia.

PMID- 22157690
TI  - An unusual tracheal polyp:  a case report.

PMID- 22157691
TI  - Comparing digital and optical microscopy diagnoses of breast and prostate core
      biopsies.

PMID- 22157692
TI  - Caldesmon is useful in demonstrating extramural venous invasion in colorectal
      carcinomas showing mucinous differentiation.

PMID- 22157693
TI  - Adult rhabdomyoma of the tongue in a child.

PMID- 22157694
TI  - Malignant paraganglioma of the pancreas.

PMID- 22157695
TI  - Establishment of a conversion factor for the Cepheid GeneXpert BCR-ABL assay.

PMID- 22157696
TI  - Multiple copies of duplicated 1q in myelodysplastic syndrome.

PMID- 22157697
TI  - Bone marrow with gelatinous transformation associated with residual disease in
      imatinib mesylate-treated chronic myelogenous leukaemia (CML).

PMID- 22157698
TI  - Bone scintigraphy in breast cancer:  added value of hybrid SPECT-CT and its
      impact on patient management.
AB  - PURPOSE: To evaluate the incremental value of single-photon emission computed
      tomography-computed tomography (SPECT-CT) over planar scintigraphy and SPECT
      alone for equivocal bone scintigraphy lesions in patients with breast cancer and
      to assess its impact on patient management. METHODS: A total of 102 patients with
      115 equivocal lesions on planar scintigraphy underwent SPECT and SPECT-CT of
      selected volume. Images were evaluated in separate sessions to minimize recall
      bias. A scoring scale of 1-5 was used, where 1 is definitely metastatic, 2 is
      probably metastatic, 3 is indeterminate, 4 is probably benign, and 5 is
      definitely benign. With receiver operating characteristic analysis, area under
      the curves was constructed for each modality. Clinical/imaging follow-up and/or
      histopathology were taken as the reference standard. RESULTS: There were 52
      indeterminate lesions on planar scintigraphy, 15 on SPECT, and three on SPECT-CT.
      Area under the curve for SPECT-CT was significantly larger compared with planar
      scintigraphy (P<0.001) and SPECT (P=0.033). This improvement was mostly for lytic
      lesions (P<0.0001). In patients (n=67) in whom the lesions under evaluation were
      the only lesions and hence whose management was decided, SPECT-CT was superior to
      SPECT (P=0.045) and planar scintigraphy (P <0.001). CONCLUSION: SPECT-CT is
      better than planar scintigraphy and SPECT alone for characterizing equivocal bone
      scintigraphy lesions in patients with breast cancer and can have a significant
      impact on patient management.

PMID- 22157699
TI  - [Physiopathological, diagnostic and therapeutic impacts of chromosomal
      translocations in hematological malignancies].
AB  - Oncogenesis is correlated with the occurrence of multiple genomic events allowing
      cancer cells to acquire new properties, including the capacity of survival and
      proliferation with down regulated control signals. Among those genomic events,
      the study of recurrent translocations, particularly common in oncohematology, has
      allowed for a better understanding of leucemogenesis and lymphomagenesis
      mechanisms. These translocations are classically distinguished depending on their
      physiopathologic consequences. It may encode for a fusion gene leading to a
      chimeric protein, which exhibits a new activity or an aberrant one, corresponding
      in most cases to the constitutive activation of a proto-oncogene. In other cases,
      these translocations may cause abnormal expression of a proto-oncogene with a
      regular structure by a transcriptional deregulation. Beyond this highlighting
      recurrent translocations and understanding better the physiopathologic
      consequences of these chromosomal modifications has a real impact on patients.
      These cytogenetic anomalies represent an essential diagnostic tool for some
      hematologies; and pave the way for a better evaluation of the prognosis and thus,
      a better adaptation of the therapeutic strategy. They also contributed to improve
      survival with the development of targeted therapies. Finally, thanks to
      cytogenetic techniques combined to molecular biology techniques, cytogenetic
      aberrations can be used as a marker of response, which allowed a monitoring of
      residual disease.

PMID- 22157700
TI  - Work-related musculoskeletal disorders are associated with impaired presenteeism
      in allied health care professionals.
AB  - OBJECTIVE: The objective of this research was to determine the impact of work
      related musculoskeletal disorders (WMSD) on presenteeism in allied health care
      professionals. METHODS: Data were collected via postal questionnaires. Work
      related musculoskeletal disorders were assessed using an established instrument
      and case definition. Data on presenteeism were collected with the Stanford
      Presenteeism Scale (13-item version). The association between WMSD and
      presenteeism was assessed with a Mann-Whitney U test. RESULTS: The response rate
      was 76%. About 48% of therapists reported WMSD in the past 4 weeks (n = 712).
      Moderate WMSD were associated with higher levels of presenteeism than minor WMSD.
      Both work impairment and work output were affected by WMSD. CONCLUSIONS: Work
      related musculoskeletal disorders may impact presenteeism in these populations.
      Costs associated with presenteeism due to WMDS may be substantial.

PMID- 22157701
TI  - Occupation and the prevalence of respiratory health symptoms and conditions: the
      Atherosclerosis Risk in Communities Study.
AB  - OBJECTIVES: To examine associations between occupation and respiratory health in
      a large, population-based cohort of adults in the United States. METHODS: Data
      from 15,273 participants, aged 45 to 64 years, in the Atherosclerosis Risk in
      Communities study were used to examine associations of current or most recent job
      held with the prevalence of self-reported chronic cough, chronic bronchitis,
      wheezing, asthma, and measures of lung function collected by spirometry. RESULTS:
      Eleven percent of participants reported wheezing and 9% were classified as having
      airway obstruction. Compared with individuals in managerial and administrative
      jobs, increased prevalences of respiratory outcomes were observed among
      participants in selected occupations, including construction and extractive
      trades (wheezing, prevalence ratio = 1.92, 95% confidence interval = 1.35, 2.73;
      airway obstruction, prevalence ratio = 1.31, 95% confidence interval = 1.05,
      1.65). CONCLUSIONS: Specific occupations are associated with adverse respiratory
      health.

PMID- 22157702
TI  - Imaging neuronal responses in slice preparations of vomeronasal organ expressing
      a genetically encoded calcium sensor.
AB  - The vomeronasal organ (VNO) detects chemosensory signals that carry information
      about the social, sexual and reproductive status of the individuals within the
      same species. These intraspecies signals, the pheromones, as well as signals from
      some predators, activate the vomeronasal sensory neurons (VSNs) with high levels
      of specificity and sensitivity. At least three distinct families of G-protein
      coupled receptors, V1R, V2R and FPR, are expressed in VNO neurons to mediate the
      detection of the chemosensory cues. To understand how pheromone information is
      encoded by the VNO, it is critical to analyze the response profiles of individual
      VSNs to various stimuli and identify the specific receptors that mediate these
      responses. The neuroepithelia of VNO are enclosed in a pair of vomer bones. The
      semi-blind tubular structure of VNO has one open end (the vomeronasal duct)
      connecting to the nasal cavity. VSNs extend their dendrites to the lumen part of
      the VNO, where the pheromone cues are in contact with the receptors expressed at
      the dendritic knobs. The cell bodies of the VSNs form pseudo-stratified layers
      with V1R and V2R expressed in the apical and basal layers respectively. Several
      techniques have been utilized to monitor responses of VSNs to sensory stimuli.
      Among these techniques, acute slice preparation offers several advantages. First,
      compared to dissociated VSNs, slice preparations maintain the neurons in their
      native morphology and the dendrites of the cells stay relatively intact. Second,
      the cell bodies of the VSNs are easily accessible in coronal slice of the VNO to
      allow electrophysiology studies and imaging experiments as compared to whole
      epithelium and whole-mount preparations. Third, this method can be combined with
      molecular cloning techniques to allow receptor identification. Sensory
      stimulation elicits strong Ca2+ influx in VSNs that is indicative of receptor
      activation. We thus develop transgenic mice that express G-CaMP2 in the olfactory
      sensory neurons, including the VSNs. The sensitivity and the genetic nature of
      the probe greatly facilitate Ca2+ imaging experiments. This method has eliminated
      the dye loading process used in previous studies. We also employ a ligand
      delivery system that enables application of various stimuli to the VNO slices.
      The combination of the two techniques allows us to monitor multiple neurons
      simultaneously in response to large numbers of stimuli. Finally, we have
      established a semi-automated analysis pipeline to assist image processing.

PMID- 22157703
TI  - Age, eGFR, and CKD complications.

PMID- 22157704
TI  - Influence of reporting methods of outcomes across transplant centers.

PMID- 22157705
TI  - FGF23 beyond mineral metabolism: a bridge to cardiovascular disease.

PMID- 22157706
TI  - Lipoprotein subfractions and particle size in end-stage renal disease.

PMID- 22157707
TI  - Profiling of autoantibodies in IgA nephropathy, an integrative antibiomics
      approach.
AB  - BACKGROUND AND OBJECTIVES: IgG commonly co-exists with IgA in the glomerular
      mesangium of patients with IgA nephropathy (IgAN) with unclear clinical
      relevance. Autoantibody (autoAb) biomarkers to detect and track progression of
      IgAN are an unmet clinical need. The objective of the study was to identify IgA
      specific autoAbs specific to IgAN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      High-density protein microarrays were evaluated IgG autoAbs in the serum of IgAN
      patients (n = 22) and controls (n = 10). Clinical parameters, including annual
      GFR and urine protein measurements, were collected on all patients over 5 years.
      Bioinformatic data analysis was performed to select targets for further
      validation by immunohistochemistry (IHC). RESULTS: One hundred seventeen (1.4%)
      specific antibodies were increased in IgAN. Among the most significant were the
      autoAb to the Ig family of proteins. IgAN-specific autoAbs (approximately 50%)
      were mounted against proteins predominantly expressed in glomeruli and tubules,
      and selected candidates were verified by IHC. Receiver operating characteristic
      analysis of our study demonstrated that IgG autoAb levels (matriline 2, ubiquitin
      conjugating enzyme E2W, DEAD box protein, and protein kinase D1) might be used in
      combination with 24-hour proteinuria to improve prediction of the progression of
      IgAN (area under the curve = 0.86, P = 0.02). CONCLUSIONS: IgAN is associated
      with elevated IgG autoAbs to multiple proteins in the kidney. This first analysis
      of the repertoire of autoAbs in IgAN identifies novel, immunogenic protein
      targets that are highly expressed in the kidney glomerulus and tubules that may
      bear relevance in the pathogenesis and progression of IgAN.

PMID- 22157708
TI  - Inverse relationship between the inflammatory marker pentraxin-3, fat body mass,
      and abdominal obesity in end-stage renal disease.
AB  - BACKGROUND AND OBJECTIVES: Pentraxin-3 (PTX3) belongs to the same pentraxin
      superfamily of acute-phase reactants as C-reactive protein (CRP). Abdominal fat
      accumulation in ESRD is considered a chronic inflammatory state, but the
      relationship of PTX3 to this phenomenon is unknown. This study assesses plausible
      associations between PTX3 and surrogates of fat mass deposits in dialysis
      patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Circulating levels of
      PTX3, CRP, and IL-6 were cross-sectionally analyzed in relation to anthropometric
      and nutritional surrogate markers of fat tissue in two cohorts comprising 156
      prevalent hemodialysis (HD) and 216 incident dialysis patients. RESULTS: In both
      cohorts, PTX3 was negatively associated with body mass index (BMI) and fat body
      mass index (FBMI) derived from anthropometrics and leptin, whereas there was a
      positive association with adiponectin. In prevalent HD patients, those with
      larger waist circumference (above gender-specific median values) had lower PTX3,
      higher CRP, and higher IL-6 levels. This was also true in multivariate analyses.
      In both cohorts, multivariate regression analyses showed that PTX3 was negatively
      and CRP (or IL-6) was positively associated with FBMI. CONCLUSIONS: Although CRP
      and IL-6 were directly associated with body fat, PTX3 levels showed negative
      correlations with surrogates of adipose tissue in two independent cohorts of ESRD
      patients. Understanding the underlying reasons behind these opposite associations
      may have clinical relevance given the survival advantage described for obese
      patients on dialysis.

PMID- 22157709
TI  - Chronic kidney disease and coronary artery vulnerable plaques.
AB  - BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is a risk factor of
      cardiovascular disease. The number of yellow plaques is a predictor of future
      cardiovascular events. We assumed that CKD might raise the risk of cardiovascular
      events by increasing the number of yellow plaques. Therefore, we compared the
      number of yellow plaques between patients with and without CKD. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Consecutive 136 patients with acute myocardial
      infarction who received percutaneous coronary intervention (PCI) and angioscopic
      examination were analyzed. The infarct-related artery was angioscopically
      examined. The number of yellow plaques, maximum yellow color grade of detected
      yellow plaques, and prevalence of disrupted yellow plaques in nonculprit segments
      were compared between patients with and without CKD. RESULTS: The number of
      yellow plaques was significantly larger in CKD than in non-CKD patients (median
      [interquartile range]: 4.0 [2.0 to 6.0] versus 2.0 [1.0 to 4.0], P = 0.001).
      Maximum yellow color grade and prevalence of disrupted plaques in the nonculprit
      segments were not different between patients with and without CKD. Multivariate
      logistic regression analysis revealed CKD as an independent risk of multiple
      yellow plaques per vessel (odds ratio 3.49, 95% confidence interval 1.10 to
      11.10, P = 0.03). CONCLUSION: CKD was an independent risk factor of multiple
      coronary yellow plaques, suggesting that patients with CKD would have a higher
      risk of coronary events because they had more yellow plaques than patients
      without CKD.

PMID- 22157710
TI  - Validation study of oxford classification of IgA nephropathy: the significance of
      extracapillary proliferation.
AB  - BACKGROUND AND OBJECTIVES The Oxford classification of IgA nephropathy (IgAN)
      includes mesangial hypercellularity, endocapillary hypercellularity, segmental
      glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as
      prognosticators. The value of extracapillary proliferation (Ex) was not
      addressed. Because the Oxford classification excludes patients with urinary
      protein <0.5 g/d and eGFR <30 ml/min per 1.73 m(2) at biopsy, the significance of
      Ex should be confirmed by validation cohorts that include more rapidly
      progressive cases. We present such a study. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: The significance of pathologic features for development end-stage
      renal failure (ESRF) was examined by multivariate analysis in 702 patients with
      IgAN. The association of Ex with kidney survival was examined by univariate
      analysis in 416 patients who met the Oxford criteria and 286 who did not,
      separately. RESULTS: In a multivariate model, S and T were significantly
      associated with ESRF. With addition of Ex, not S but Ex was significant for ESRF.
      In univariate analysis, kidney survival was significantly lower in patients with
      Ex than in those without, in patients who did not meet the Oxford criteria, but
      such a difference was not found in patients who met it. CONCLUSIONS: The
      prognostic significance of Ex was evident in our cohort. It seems that Ex did not
      emerge from the Oxford classification as a prognosticator because of exclusion of
      severe cases (eGFR <30 ml/min per 1.73 m(2)). We suggest that extracapillary
      proliferation be included in the next version of the Oxford classification of
      IgAN to widen the scope of the classification.

PMID- 22157711
TI  - The anion gap and routine serum protein measurements in monoclonal gammopathies.
AB  - BACKGROUND AND OBJECTIVES: An abnormal anion gap and an increased total protein
      and globulin are clues to the diagnosis of monoclonal gammopathy. We explored the
      utility of these markers in IgG, IgA, IgM, and free light chain monoclonal
      gammopathies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The anion gap, Na(+)
      - (Cl(-) + HCO(3)(-)), corrected for hypoalbuminemia, was calculated in patients
      with monoclonal gammopathies. Exclusion criteria were serum calcium >10.5 mg/dl
      and/or creatinine >2 mg/dl. RESULTS: Among 287 patients, 242 remained after
      applying exclusion criteria (109 IgG, 64 IgA, 21 IgM, and 48 light chain); 36% of
      242 patients required correction for hypoalbuminemia. The anion gap was decreased
      (<10) in 22% of IgG and increased (>15) in 31% of IgA monoclonal gammopathies.
      IgM did not affect the gap. In light chain gammopathies, the anion gap showed no
      consistent trend (15% increased, 17% decreased). Mean clonal IgG, IgA, and IgM
      concentrations were 10-fold higher than mean clonal free light chain
      concentrations in the respective monoclonal gammopathies (P < 0.001). These
      paraprotein level disparities were reflected in significantly increased mean
      serum total protein and globulin concentrations in IgG, IgA, and IgM versus free
      light chain monoclonal gammopathies, where mean total protein and globulin levels
      were within normal limits (P < 0.001). CONCLUSIONS: The anion gap was
      significantly altered in IgG and IgA monoclonal gammopathies, but it was not a
      sensitive tool for suspecting the diagnosis. In light chain monoclonal
      gammopathies, the anion gap, total protein, and globulin did not provide reliable
      diagnostic clues.

PMID- 22157712
TI  - Low-molecular-weight proteins as prognostic markers in idiopathic membranous
      nephropathy.
AB  - BACKGROUND: Accurate prediction of prognosis in idiopathic membranous nephropathy
      (iMN) allows restriction of immunosuppressive therapy to patients at high risk
      for ESRD. Here we re-evaluate urinary low-molecular-weight proteins as prognostic
      markers and explore causes of misclassification. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: In a cohort of 129 patients with serum creatinine concentration
      <135 MUmol/L and proteinuria >=3.0 g/10 mmol, urinary alpha1- (ualpha1m) and
      beta2-microglobulin (ubeta2m) excretion rate was determined. Urinary alpha1m and
      ubeta2m-creatinine ratio was also obtained. We defined progression as a rise in
      serum creatinine >=50% or >=25% and an absolute level >=135 MUmol/L. RESULTS:
      Median survival time was 25 months, and 47% of patients showed progression. The
      area under the receiver operating characteristic curve for ubeta2m was 0.81 (95%
      CI: 0.73 to 0.89). Using a threshold value of 1.0 MUg/min, sensitivity and
      specificity were 73% and 75%, respectively. Similar accuracy was observed for the
      ubeta2m-creatinine ratio with sensitivity and specificity of 75% and 73%,
      respectively, at a threshold of 1.0 MUg/10 mmol creatinine. Similar accuracy was
      found for ualpha1m and ualpha1m-creatinine ratio. Blood Pressure and cholesterol
      contributed to misclassification. Repeated measurements improved accuracy in
      patients with persistent proteinuria: the positive predictive value of ubeta2m
      increased from 72% to 89% and the negative predictive value from 76% to 100%.
      CONCLUSIONS: Urinary excretion of ualpha2m and ubeta2m predict prognosis in iMN.
      A spot urine sample can be used instead of a timed sample. A repeated measurement
      after 6 to 12 months increases prognostic accuracy.

PMID- 22157713
TI  - Infectious complications in kidney-transplant recipients desensitized with
      rituximab and intravenous immunoglobulin.
AB  - BACKGROUND AND OBJECTIVES: Rituximab and intravenous Ig (IVIG) are commonly used
      for desensitization of HLA and blood group-incompatible (ABOi) transplants.
      However, serious infections have been noted in association with rituximab
      administration. In this study, we retrospectively compared infectious outcomes in
      those who received rituximab plus IVIG for HLA or ABOi transplants (RIT group)
      with a group of nonsensitized, ABO-compatible transplant recipients (non-RIT
      group). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients undergoing kidney
      transplantation at Cedars-Sinai Medical Center were included in the analysis. A
      total of 361 patients were identified. All received antimicrobial prophylaxis and
      viral surveillance. The primary outcome was infection. RESULTS: Overall patient
      survival was 97 and 96%, and graft survival was 91 and 89% in the RIT and non-RIT
      groups, respectively, after an average follow-up of 18 months. There were equal
      rates of bacterial (34.7% versus 39.1%), viral (21.8% versus 25.1%), fungal (5.9%
      versus 5.2%), and serious infections (22.9% versus 25.5%) in the RIT and non-RIT
      groups respectively. Urinary tract infection was the most common infection,
      accounting for 50% of all bacterial infections. Cytomegalovirus viremia was
      nonsignificantly more common in the nonrituximab-treated group (15.2% versus
      10%), whereas BK viremia was marginally more frequent in the rituximab-treated
      group (10.6% versus 5.8%). There were no graft losses caused by BK-associated
      nephropathy. There were two deaths in each group related to infection (1%).
      CONCLUSION: Rituximab does not increase infection risk when used with intravenous
      Ig for desensitization.

PMID- 22157714
TI  - ErbB2 and ErbB3 regulate recovery from dextran sulfate sodium-induced colitis by
      promoting mouse colon epithelial cell survival.
AB  - ErbB2 and ErbB3 receptor tyrosine kinases are key regulators of proliferation,
      migration, differentiation and cell survival; however, their roles in
      gastrointestinal biology remain poorly defined. We hypothesized that ErbB2 and
      ErbB3 promote colon epithelial cell survival in the context of the wound-healing
      response following colitis. In this study, mice bearing intestinal epithelial
      specific deletion of ErbB2 or ErbB3 were treated with dextran sulfate sodium
      (DSS). Colon sections were examined for injury, cytokine expression, epithelial
      cell proliferation and apoptosis. Deletion of epithelial ErbB2 did not affect the
      extent of intestinal injury in response to DSS, whereas deletion of ErbB3
      slightly increased injury. However, the roles of both receptors were more
      apparent during recovery from DSS colitis, in which ErbB2 or ErbB3 epithelial
      deletion resulted in greater inflammation and crypt damage during the early
      reparative period. Moreover, loss of ErbB3 prevented normal epithelial
      regeneration in the long term, with damage persisting for at least 6 weeks
      following a single round of DSS. Delayed recovery in mice with epithelial
      deletion of ErbB2 or ErbB3 was associated with increased colonic expression of
      tumor necrosis factor alpha and increased epithelial apoptosis. Furthermore,
      epithelial ErbB3 deletion increased apoptosis at baseline and during DSS injury.
      Additionally, epithelial cell hyperproliferation during recovery was exacerbated
      by deletion of either ErbB2 or ErbB3. These results suggest that ErbB2 and ErbB3
      have important cytoprotective and reparative roles in the colonic epithelium
      following injury, by promoting colon epithelial cell survival.

PMID- 22157715
TI  - A pyrosequencing assay for the quantitative methylation analysis of the PCDHB
      gene cluster, the major factor in neuroblastoma methylator phenotype.
AB  - Epigenetic alterations are hallmarks of cancer and powerful biomarkers, whose
      clinical utilization is made difficult by the absence of standardization and of
      common methods of data interpretation. The coordinate methylation of many loci in
      cancer is defined as 'CpG island methylator phenotype' (CIMP) and identifies
      clinically distinct groups of patients. In neuroblastoma (NB), CIMP is defined by
      a methylation signature, which includes different loci, but its predictive power
      on outcome is entirely recapitulated by the PCDHB cluster only. We have developed
      a robust and cost-effective pyrosequencing-based assay that could facilitate the
      clinical application of CIMP in NB. This assay permits the unbiased simultaneous
      amplification and sequencing of 17 out of 19 genes of the PCDHB cluster for
      quantitative methylation analysis, taking into account all the sequence
      variations. As some of these variations were at CpG doublets, we bypassed the
      data interpretation conducted by the methylation analysis software to assign the
      corrected methylation value at these sites. The final result of the assay is the
      mean methylation level of 17 gene fragments in the protocadherin B cluster
      (PCDHB) cluster. We have utilized this assay to compare the methylation levels of
      the PCDHB cluster between high-risk and very low-risk NB patients, confirming the
      predictive value of CIMP. Our results demonstrate that the pyrosequencing-based
      assay herein described is a powerful instrument for the analysis of this gene
      cluster that may simplify the data comparison between different laboratories and,
      in perspective, could facilitate its clinical application. Furthermore, our
      results demonstrate that, in principle, pyrosequencing can be efficiently
      utilized for the methylation analysis of gene clusters with high internal
      homologies.

PMID- 22157716
TI  - Sjogren's syndrome autoantibodies provoke changes in gene expression profiles of
      inflammatory cytokines triggering a pathway involving TACE/NF-kappaB.
AB  - We explore the association of the inflammatory gene expression profile observed
      in the chronic inflammatory autoimmune disorder Sjogren's syndrome (SS) with
      changes in TNF-alpha converting enzyme (TACE), tumor necrosis factor (TNF)-alpha
      and nuclear factor (NF)-kappaB levels showing that pathways that include TNF
      alpha signaling converge on NF-kappaB contributing to exacerbate the diseases.
      The treatment of human salivary gland epithelial cells (SGECs) with SS anti
      Ro/SSA autoantibodies (Abs) result in a progressive increase in NF-kappaB-DNA
      binding, that includes a marked enhancement in NF-kappaB subunit p65 protein-DNA
      binding. A human cytokine multi-analyte array demonstrated that the NF-kappaB
      proinflammatory target genes, increased by anti-Ro/SSA Abs treatment, includes
      CXC chemokines (CXCL1, CXCL6 and CXCL9), CC chemokines (CCL2, CCL13 and CCL20),
      interleukins (IL-1alpha, IL-1beta, IL-1F8, IL-6, IL-8, IL-9, IL-13, IL-17 and IL
      22) and their receptors (IL-1RN, IL-10Ralpha, IL-13Ralpha, CCR1, CCR2, CCR3, CCR4
      and CXCR1). Blockade of TACE through the use of the specific inhibitor TAPI-1
      regulates proinflammatory cytokines production in SGEC treated with anti-Ro/SSA
      Abs inhibiting NF-kappaB nuclear translocation and activation. To further
      investigate the role of NF-kappaB on anti-Ro/SSA Abs-determined proinflammatory
      gene expression, we used the inhibitory protein IkappaB-alpha dominant negative
      super-repressor as inhibitor of NF-kappaB-DNA binding, demonstrating that
      transfection with dominant-negative IkappaB-alpha in anti-Ro/SSA-treated SGEC
      determined a marked reduction of proinflammatory cytokines gene expression.
      Although further studies are needed to clarify the mechanisms underlying SS, our
      results demonstrate that SS Abs exert their pathogenic effects via triggering the
      TACE/TNF-alpha/NF-kappaB axis.

PMID- 22157718
TI  - Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial
      alterations in mouse liver.
AB  - Although carbon tetrachloride (CCl(4))-induced acute and chronic hepatotoxicity
      have been extensively studied, little is known about the very early in vivo
      effects of this organic solvent on oxidative stress and mitochondrial function.
      In this study, mice were treated with CCl(4) (1.5 ml/kg ie 2.38 g/kg) and
      parameters related to liver damage, lipid peroxidation, stress/defense and
      mitochondria were studied 3 h later. Some CCl(4)-intoxicated mice were also
      pretreated with the cytochrome P450 2E1 inhibitor diethyldithiocarbamate or the
      antioxidants Trolox C and dehydroepiandrosterone. CCl(4) induced a moderate
      elevation of aminotransferases, swelling of centrilobular hepatocytes, lipid
      peroxidation, reduction of cytochrome P4502E1 mRNA levels and a massive increase
      in mRNA expression of heme oxygenase-1 and heat shock protein 70. Moreover,
      CCl(4) intoxication induced a severe decrease of mitochondrial respiratory chain
      complex IV activity, mitochondrial DNA depletion and damage as well as
      ultrastructural alterations. Whereas DDTC totally or partially prevented all
      these hepatic toxic events, both antioxidants protected only against liver lipid
      peroxidation and mitochondrial damage. Taken together, our results suggest that
      lipid peroxidation is primarily implicated in CCl(4)-induced early mitochondrial
      injury. However, lipid peroxidation-independent mechanisms seem to be involved in
      CCl(4)-induced early hepatocyte swelling and changes in expression of
      stress/defense-related genes. Antioxidant therapy may not be an efficient
      strategy to block early liver damage after CCl(4) intoxication.

PMID- 22157717
TI  - CD133+ colon cancer cells are more interactive with the tumor microenvironment
      than CD133- cells.
AB  - Experimental data indicate that colorectal cancer cells with CD133 expression
      exhibit enhanced tumorigenicity over CD133-negative (CD133-) cells. We
      hypothesized that CD133-positive (CD133+) cells, compared with CD133-, are more
      tumorigenic because they are more interactive with and responsive to their
      stromal microenvironment. Freshly dissected and dissociated cells from a primary
      colon cancer were separated into carcinoma-associated fibroblasts (CAF) and the
      epithelial cells; the latter were further separated into CD133+ and CD133- cells
      using fluorescence-activated cell sorter. The CD133+ cells formed large tumors in
      non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice, demonstrating
      the phenotypic cellular diversity of the original tumor, whereas CD133- cells
      were unable to sustain significant growth. Affymetrix gene array analyses using t
      test, fold-change and multiple test correction identified candidate genes that
      were differentially expressed between the CD133+ vs CD133- cells. RT-PCR verified
      differences in expression for 30 of the 46 genes selected. Genes upregulated (+
      vs - cells) included CD133 (9.3-fold) and CXCR4 (4-fold), integrin beta8 and
      fibroblast growth factor receptor 2. The CAF highly express the respective
      ligands: stromal-derived factor-1 (SDF-1), vitronectin and FGF family members,
      suggesting a reciprocal relationship between the CD133+ and CAF cells. SDF-1
      caused an increase in intracellular calcium in cells expressing both CD133 and
      CXCR4, confirming functional CXCR4. The CD133+/CXCR4+ phenotype is increased to
      32% when the cells are grown in suspension compared with only 9% when the cells
      were allowed to attach. In Matrigel 3-D culture, the CD133+/CXCR4+ group treated
      with SDF-1 grew more colonies compared with vehicle, as well as significantly
      larger colony sizes of tumor spheres. These data demonstrate proof of principle
      that the enhanced tumorigenic potential of CD133+, compared with CD133-, cells is
      due to their increased ability to interact with their neighboring CAF.

PMID- 22157719
TI  - Multiple roles of the epithelium-specific ETS transcription factor, ESE-1, in
      development and disease.
AB  - The E26 transformation-specific (ETS) family of transcription factors comprises
      of 27 and 26 members in humans and mice, respectively, which are known to
      regulate many different biological processes, including cell proliferation, cell
      differentiation, embryonic development, neoplasia, hematopoiesis, angiogenesis,
      and inflammation. The epithelium-specific ETS transcription factor-1 (ESE-1) is a
      physiologically important ETS transcription factor, which has been shown to play
      a role in the pathogenesis of various diseases, and was originally characterized
      as having an epithelial-restricted expression pattern, thus placing it within the
      epithelium-specific ETS subfamily. Despite a large body of published work on ETS
      biology, much remains to be learned about the precise functions of ESE-1 and
      other epithelium-specific ETS factors in regulating diverse disease processes.
      Clues as to the specific function of ESE-1 in the setting of various diseases can
      be obtained from studies aimed at examining the expression of putative target
      genes regulated by ESE-1. Thus, this review will focus primarily on the various
      roles of ESE-1 in different pathophysiological processes, including regulation of
      epithelial cell differentiation during both intestinal development and lung
      regeneration; regulation of dendritic cell-driven T-cell differentiation during
      allergic airway inflammation; regulation of mammary gland development and breast
      cancer; and regulation of the effects of inflammatory stimuli within the setting
      of synovial joint and vascular inflammation. Understanding the exact mechanisms
      by which ESE-1 regulates these processes can have important implications for the
      treatment of a wide range of diseases.

PMID- 22157720
TI  - Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic
      cells and expressed selectively in tissue granulomas and foam cells.
AB  - Granulomatous inflammations, characterized by the presence of activated
      macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to
      recognize. However, in ambiguous cases the use of a MA marker that expresses
      selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM),
      a MA-differentiation marker, is preferentially induced in EPCs of all granuloma
      types studied, but not in resting MAs. As CPM is not expressed constitutively in
      MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute
      granuloma detection when dense non-granulomatous MAs are also present. Despite
      this rule, hardly any detectable CPM was found in advanced/active tubercle
      caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM.
      Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs
      were infected with live mycobacteria. In vitro, MA-CPM transcript is neither
      induced remarkably by interferon-gamma, known to cause classical MA activation,
      nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed
      in lipid-laden MAs, including the foam cells of atherosclerotic plaques,
      xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and
      low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in
      vitro in monocyte-derived MAs both at transcriptional and protein levels, and the
      increase is repressed under lipid-depleted conditions. The microarray analyses
      support the notion that CPM induction correlates with a robust progressive
      increase in CPM gene expression during monocyte to MA maturation and dendritic
      cell (DC) differentiation mediated by granulocyte-MA-colony-stimulating factor+IL
      4. M-CSF alone also induced CPM. These results collectively indicate that CPM
      upregulation in MAs is preferentially associated with increased lipid uptake, and
      exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is
      useful for granuloma and foam MA detections in tissue sections. Furthermore, the
      present data offer CPM for the first time to be a novel marker and cellular
      player in lipid uptake and/or metabolism of MAs by promoting foam cell formation.

PMID- 22157721
TI  - Heparin-binding EGF-like growth factor protects intestinal stem cells from injury
      in a rat model of necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is an often catastrophic disease that typically
      affects premature newborns. Although the exact etiology of NEC is uncertain, the
      disease is associated with formula feeding, bacterial colonization of the gut,
      hypoxia and hypoperfusion. In light of the pathogenesis of NEC, the integrity and
      function of the intestinal mucosa has a major defensive role against the
      initiation of NEC. Various forms of intestinal injury, including NEC, injure the
      intestinal epithelial cell (IEC) lineages, including the intestinal stem cells
      (ISCs), thereby disrupting the normal homeostasis needed to maintain gut barrier
      function. In the current study, we examined the effects of heparin-binding EGF
      like growth factor (HB-EGF) administration on enterocytes, goblet cells,
      neuroendocrine cells and ISCs in a newborn rat model of experimental NEC. We also
      examined the cytoprotective effects of HB-EGF on ISCs in in vitro cell cultures
      and in ex vivo crypt-villous organoid cultures. We found that HB-EGF protects all
      IEC lineages, including ISCs, from injury. We further found that HB-EGF protects
      isolated ISCs from hypoxic injury in vitro, and promotes ISC activation and
      survival, and the expansion of crypt transit-amplifying cells, in ex vivo crypt
      villous organoid cultures. The protective effects of HB-EGF were dependent on EGF
      receptor activation, and were mediated via the MEK1/2 and PI3K signaling
      pathways. These results show that the intestinal cytoprotective effects of HB-EGF
      are mediated, at least in part, through its ability to protect ISCs from injury.

PMID- 22157722
TI  - WZ4002, a third-generation EGFR inhibitor, can overcome anoikis resistance in
      EGFR-mutant lung adenocarcinomas more efficiently than Src inhibitors.
AB  - Src has a role in the anoikis resistance in lung adenocarcinomas. We focused on
      two epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cell
      lines, HCC827 (E746-A750 deletion) and H1975 (L858R+T790M), in suspension to
      elucidate whether suspended lung adenocarcinoma cells are eradicated by long-term
      treatment with Src tyrosine kinase inhibitors (TKIs). We also examined metastasis
      positive lymph nodes from 16 EGFR-mutant lung adenocarcinoma patients for
      immunohistochemical expression of mutant-specific EGFR. Almost all suspended
      HCC827 cells underwent apoptosis after 144 h of combination treatment with
      AZD0530, trichostatin A (TSA), and ABT-263, whereas many suspended H1975 cells
      survived the treatment. AZD0530 is a Src TKI, TSA is a histone deacetylase
      inhibitor, and ABT-263 is a Bcl-2 inhibitor. During the therapy, the
      phosphorylation of EGFR decreased in HCC827 cells and remained stable in H1975
      cells. The phosphorylated EGFR of Src TKI-resistant H1975 cells, as well as
      HCC827 cells, was completely suppressed by the third generation EGFR TKI, WZ4002.
      Consequently, both the suspended cell lines were almost completely eradicated
      within 144 h, with the combined therapy of WZ4002, ABT-263, and TSA.
      Interestingly, treated suspended cells underwent apoptosis to a greater extent
      than did adherent cells. Intrasinus floating lung adenocarcinoma cells in the
      lymph nodes expressed a mutant-specific EGFR. These findings suggest that
      suspended EGFR-mutant lung adenocarcinoma cells depend significantly more on EGFR
      activation for survival than attached cells do. The tumor cells circulating in
      vessels, which express mutant-specific EGFR, would be highly susceptible to the
      combination therapy of WZ4002, ABT-263, and TSA.

PMID- 22157723
TI  - Bisoprolol delays progression towards right heart failure in experimental
      pulmonary hypertension.
AB  - BACKGROUND: In pulmonary arterial hypertension (PH), sympathetic adrenergic
      activity is highly elevated. Sympathetic overactivity is a compensatory mechanism
      at first, but might be detrimental for cardiac function in the long run. We
      therefore investigated whether chronic low-dose treatment with bisoprolol (a
      cardioselective beta-blocker) has beneficial effects on cardiac function in
      experimental PH. METHODS AND RESULTS: PH was induced in rats by a single
      injection of monocrotaline (60 mg/kg). Pressure telemetry in PH rats revealed
      that 10 mg/kg bisoprolol was the lowest dose that blunted heart rate response
      during daily activity. Ten days after monocrotaline injection, echocardiography
      was performed and PH rats were randomized for bisoprolol treatment (oral gavage)
      or vehicle (n=7/group). At end of study (body mass loss >5%), echocardiography
      was repeated, with additional pressure-volume measurements and histomolecular
      analyses. Compared with control, right ventricular (RV) systolic pressure and
      arterial elastance (measure of vascular resistance) more than tripled in PH.
      Bisoprolol delayed time to right heart failure (P<0.05). RV afterload was
      unaffected, however, bisoprolol treatment increased RV contractility and filling
      (both P<0.01), and partially restored right ventriculo-arterial coupling and
      cardiac output (both P<0.05). Bisoprolol restored RV beta-adrenergic receptor
      signaling. Histology revealed significantly less RV fibrosis and myocardial
      inflammation in bisoprolol treated PH rats. CONCLUSIONS: In experimental PH,
      treatment with bisoprolol delays progression toward right heart failure, and
      partially preserves RV systolic and diastolic function. These promising results
      suggest a therapeutic role for beta-blockers in PH that warrants further clinical
      investigation.

PMID- 22157724
TI  - Local electrical potential detection of DNA by nanowire-nanopore sensors.
AB  - Nanopores could potentially be used to perform single-molecule DNA sequencing at
      low cost and with high throughput. Although single base resolution and
      differentiation have been demonstrated with nanopores using ionic current
      measurements, direct sequencing has not been achieved because of the difficulties
      in recording very small (~pA) ionic currents at a bandwidth consistent with fast
      translocation speeds. Here, we show that solid-state nanopores can be combined
      with silicon nanowire field-effect transistors to create sensors in which
      detection is localized and self-aligned at the nanopore. Well-defined field
      effect transistor signals associated with DNA translocation are recorded when an
      ionic strength gradient is imposed across the nanopores. Measurements and
      modelling show that field-effect transistor signals are generated by highly
      localized changes in the electrical potential during DNA translocation, and that
      nanowire-nanopore sensors could enable large-scale integration with a high
      intrinsic bandwidth.

PMID- 22157725
TI  - Synthetically programmable nanoparticle superlattices using a hollow three
      dimensional spacer approach.
AB  - Crystalline nanoparticle arrays and superlattices with well-defined geometries
      can be synthesized by using appropriate electrostatic, hydrogen-bonding or
      biological recognition interactions. Although superlattices with many distinct
      geometries can be produced using these approaches, the library of achievable
      lattices could be increased by developing a strategy that allows some of the
      nanoparticles within a binary lattice to be replaced with 'spacer' entities that
      are constructed to mimic the behaviour of the nanoparticles they replace, even
      though they do not contain an inorganic core. The inclusion of these spacer
      entities within a known binary superlattice would effectively delete one set of
      nanoparticles without affecting the positions of the other set. Here, we show how
      hollow DNA nanostructures can be used as 'three-dimensional spacers' within
      nanoparticle superlattices assembled through programmable DNA interactions. We
      show that this strategy can be used to form superlattices with five distinct
      symmetries, including one that has never before been observed in any crystalline
      material.

PMID- 22157726
TI  - Enhanced and switchable nanoscale thermal conduction due to van der Waals
      interfaces.
AB  - Understanding thermal transport in nanostructured materials is important for the
      development of energy conversion applications and the thermal management of
      microelectronic and optoelectronic devices. Most nanostructures interact through
      van der Waals interactions, and these interactions typically lead to a reduction
      in thermal transport. Here, we show that the thermal conductivity of a bundle of
      boron nanoribbons can be significantly higher than that of a single free-standing
      nanoribbon. Moreover, the thermal conductivity of the bundle can be switched
      between the enhanced values and that of a single nanoribbon by wetting the van
      der Waals interface between the nanoribbons with various solutions.

PMID- 22157727
TI  - A surface-anchored molecular four-level conductance switch based on single proton
      transfer.
AB  - The development of a variety of nanoscale applications requires the fabrication
      and control of atomic or molecular switches that can be reversibly operated by
      light, a short-range force, electric current or other external stimuli. For such
      molecules to be used as electronic components, they should be directly coupled to
      a metallic support and the switching unit should be easily connected to other
      molecular species without suppressing switching performance. Here, we show that a
      free-base tetraphenyl-porphyrin molecule, which is anchored to a silver surface,
      can function as a molecular conductance switch. The saddle-shaped molecule has
      two hydrogen atoms in its inner cavity that can be flipped between two states
      with different local conductance levels using the electron current through the
      tip of a scanning tunnelling microscope. Moreover, by deliberately removing one
      of the hydrogens, a four-level conductance switch can be created. The resulting
      device, which could be controllably integrated into the surrounding nanoscale
      environment, relies on the transfer of a single proton and therefore contains the
      smallest possible atomistic switching unit.

PMID- 22157728
TI  - Hypersensitivity syndrome with olanzapine confirmed by patch tests.

PMID- 22157729
TI  - Prediction of the postoperative pulmonary function in lung cancer patients with
      borderline function using ventilation-perfusion scintigraphy.
AB  - OBJECTIVE: To predict the postoperative pulmonary function using ventilation
      perfusion scintigraphy and explore its feasibility in evaluating surgical risk
      for lung cancer patients with borderline pulmonary functions [forced expiratory
      volume in 1 s (FEV1)<2.0 l for pneumonectomy or <1.5 l for lobectomy]. METHODS:
      Twenty lung cancer patients (52-86 years, four women, 16 men) with borderline
      pulmonary functions were included in this study. Planar ventilation scans with Tc
      diethylenetriamine pentaacetic acid aerosol and perfusion scans with Tc
      macroaggregated albumin were performed before surgery. Pulmonary function test
      was performed 1 week before surgery for all patients and 2 months after surgery
      for 12 patients. The predicted postoperative FEV1 (ppoFEV1) values were
      calculated using Neuhaus equations and compared with FEV1 values after surgery.
      RESULTS: There was no significant statistical difference between the ppoFEV1
      values resulting from the ventilation scan (ppoFEV1-V) and the ppoFEV1 values
      resulting from the perfusion scan (ppoFEV1-Q): (1.153 +/- 0.227) l versus (1.204
      +/- 0.210) l (n=20, t=0.045, P>0.05). No statistically significant difference
      existed between the ppoFEV1-V values and the postoperative FEV1 values: (1.238 +/
      0.200) l versus (1.28 +/- 0.146) l (n=12, t=0.557, P>0.05), or between the
      ppoFEV1-Q values and the postoperative FEV1 values: (1.302 +/- 0.161) l versus
      (1.28 +/- 0.146) l (n=12, t=0.288, P>0.05). Both ppoFEV1-V values and ppoFEV1-Q
      values fairly correlated with the postoperative FEV1 values (r=0.765, 0.674;
      t=3.756, 2.885, P<0.01, P<0.01). CONCLUSION: Ventilation-perfusion scans can
      predict postoperative pulmonary function and help evaluate the risk of surgery
      for lung cancer patients with borderline pulmonary functions.

PMID- 22157731
TI  - Occupational exposures and cancer of the larynx-systematic review and meta
      analysis.
AB  - OBJECTIVE: To review epidemiologic data on occupational exposures and laryngeal
      cancer. METHODS: We performed a systematic literature search and a series of meta
      analyses for agents with at least 10 available studies with homogenous exposure.
      RESULTS: We analyzed 99 publications. Significantly increased meta-relative risks
      (meta-RRs) were obtained considering exposure to polycyclic aromatic hydrocarbons
      (meta-RR 1.29; 95% confidence interval [CI] 1.10 to 1.52), engine exhaust (meta
      RR 1.17; 95% CI 1.05 to 1.30), textile dust (meta-RR 1.41; 95% CI 1.09 to 1.83),
      and working in the rubber industry (meta-RR 1.39; 95% CI 1.13 to 1.71). Exposures
      to wood dust, formaldehyde, and cement dust were not significantly associated
      with laryngeal cancer. In regards of the epidemiologic available data, we could
      not conclude on the role of solvents. CONCLUSION: Further studies should overcome
      past limitations in terms of exposure characterization, adjustment for
      confounding, and sample size.

PMID- 22157732
TI  - Enterprise restructuring and the health of employees: a cohort study.
AB  - OBJECTIVE: To examine the influence of enterprise restructuring on general health
      and emotional exhaustion, and to investigate which factors explain the relation
      between restructuring and these outcomes. METHODS: Longitudinal data of the
      Netherlands Working Conditions Cohort Study were used. At baseline and after 12
      months, 9076 employees filled out a questionnaire. Logistic regression analysis
      was applied. RESULTS: Prolonged exposure to restructuring increased the
      likelihood of poor general health, and its influence was partly explained by job
      insecurity. Emotional exhaustion was more likely among employees that experienced
      prolonged exposure to restructuring or restructuring during the past year. Job
      insecurity explained the influence of prolonged restructuring, together with job
      demands and supervisor's support. CONCLUSIONS: Prolonged exposure to
      restructuring adversely affects general health and emotional exhaustion in
      employees, and its influence seems to be explained by job insecurity.

PMID- 22157733
TI  - Scale-up of mammalian cell culture using a new multilayered flask.
AB  - A growing number of cell-based applications require large numbers of cells. Usage
      of single layer T-flasks, that are adequate during small-scale expansion, may
      become cumbersome, laborious and time-consuming when large numbers of cells are
      required. To address this need, the performance of a new multi-layered cell
      culture vessel to facilitate easy scale up of cells from single layered T-flasks
      will be discussed. The flasks tested are available in 3- and 5-layer format and
      enable culture and complete recovery of three and five times the number of cells
      respectively, compared to T-175 flasks. A key feature of the BD Multi-Flask is a
      mix/equilibration port that allows rapid in-vessel mixing as well as uniform
      distribution of cells and reagents within and between layers of each vessel and
      consistently produce cells that can be cultured in an environment that is
      congruent to T-175 flasks. The design of these Multi-Flasks also allows for
      convenient pipette access for adding reagents and cells directly into the flasks
      as well as efficient recovery of valuable cells and reagents and reduces risk of
      contamination due to pouring. For applications where pouring is preferred over
      pipetting, the design allows for minimal residual liquid retention so as to
      reduce wastage of valuable cells and reagents.

PMID- 22157734
TI  - Residual normal stem cells can be detected in newly diagnosed chronic myeloid
      leukemia patients by a new flow cytometric approach and predict for optimal
      response to imatinib.
AB  - Insensitivity of chronic myeloid leukemia (CML) hematopoietic stem cells to
      tyrosine kinase inhibitors (TKIs) prevents eradication of the disease and may be
      involved in clinical resistance. For improved treatment results more knowledge
      about CML stem cells is needed. We here present a new flow cytometric approach
      enabling prospective discrimination of CML stem cells from their normal
      counterparts within single-patient samples. In 24 of 40 newly diagnosed CML
      patients residual normal CD34(+)CD38(-) stem cells could be identified by lower
      CD34 and CD45 expression, lower forward/sideward light scatter and by differences
      of lineage marker expression (CD7, CD11b and CD56) and of CD90. fluorescent in
      situ hybridization (FISH) analysis on Fluorescence-activated cell sorting sorted
      cells proved that populations were BCR-ABL positive or negative and long-term
      liquid culture assays with subsequent colony forming unit assays and FISH
      analysis proved their stem cell character. Patients with residual non-leukemic
      stem cells had lower clinical risk scores (Sokal, Euro), lower hematological
      toxicity of imatinib (IM) and better molecular responses to IM than patients
      without. This new approach will expand our possibilities to separate CML and
      normal stem cells, present in a single bone marrow or peripheral blood sample,
      thereby offering opportunities to better identify new CML stem-cell-specific
      targets. Moreover, it may guide optimal clinical CML management.

PMID- 22157735
TI  - Highly sensitive MRD tests for ALL based on the IKZF1 Delta3-6 microdeletion.

PMID- 22157736
TI  - How to manage polycythemia vera.
AB  - My diagnostic approach in case of isolated erythrocytosis is based on the visit
      and the interview of patients, and on checking the causes of secondary
      erythrocytosis. If causes of secondary erythrocytosis are not evident and serum
      erythropoietin level is low-normal, I study JAK2 mutations. In the case of a
      patient with erythrocytosis and other signs of myeloproliferation, such as
      leukocytosis, thrombocytosis or splenomegaly, the diagnosis of polycythemia vera
      (PV) is likely, and I test serum erythropoietin and JAK2 mutations first. I
      stratify patients at diagnosis of PV according to age and history of thrombosis.
      I start hydroxyurea for patients who are at a high risk of thrombosis (that is,
      with one or two risk factors), while I continue only phlebotomy in other cases.
      All PV patients, if not contraindicated, receive aspirin. I follow up patients
      monthly until normalization of their blood cell counts or splenomegaly, and
      afterwards every 2 months with visit, cell blood count and blood smear
      evaluation. After diagnosis, I perform bone marrow biopsy only in the case of
      clinical signs of disease evolution.

PMID- 22157737
TI  - Prognostic factors for acute myeloid leukemia patients with t(6;9)(p23;q34) who
      underwent an allogeneic hematopoietic stem cell transplant.

PMID- 22157738
TI  - American Society of Regional Anesthesia and Pain Medicine 2010 Gaston Labat
      Lecture: Perineural catheter analgesia as a routine method after ambulatory
      surgery--effective but unrealistic.
AB  - Adequate postoperative analgesia is a prerequisite for successful ambulatory
      surgery and remains a challenge. The problem of pain at home may be increasing
      because previously inpatient surgical procedures are becoming ambulatory and it
      is expected that the number and complexity of ambulatory surgical procedures will
      continue to increase. In 1998, we described the use of surgical-site and
      perineural catheter techniques that allowed patients to self-administer local
      anesthetics through disposable, elastomeric pumps for pain management at home. In
      recent years, availability of improved elastometric and other lightweight pump
      devices, the general trend of avoiding strong opioids and the preference for non
      opioid analgesic techniques has led to increasing use of this technique after a
      variety of ambulatory surgical procedures. The two most common techniques are
      perineural and wound catheter infusions (WCI). Current evidence suggests that
      both are effective, although comparative studies are lacking. Perineural
      techniques are highly effective but are technically challenging and require labor
      intensive and expensive home care that can be provided only in specialized
      centers. Disappointing past experience with implementation of perineural catheter
      techniques in inpatients suggests that it is unrealistic to expect their routine
      use in most ambulatory centers. Surgical-site catheter technique is a simpler,
      safer, and less expensive alternative and therefore more likely to gain
      widespread use. Only controlled comparisons can show whether the current belief
      about the superiority of ambulatory perineural techniques over WCI is justified.
      Such studies should address technical failures, side effects, home care of the
      medically unsupervised or undersupervised patient, and cost-effectiveness to
      demonstrate which of the 2 techniques is most appropriate for a particular
      procedure.

PMID- 22157739
TI  - Ultrasound imaging to estimate risk of esophageal and vascular puncture after
      conventional stellate ganglion block.
AB  - BACKGROUND AND OBJECTIVES: The most common techniques to perform stellate
      ganglion blocks (SGBs) are the blind C6 approach and the fluoroscopic-controlled
      paratracheal C7 approach, both after manual dislocation of the large vessels.
      Complications due to vascular or esophageal puncture have been reported. The goal
      of this ultrasound imaging study was to determine how frequently hazardous
      structures are located along the needle path of conventional SGB and to determine
      the influence of the dislocation maneuver on their position. METHODS: Sixty
      volunteers were examined on both sides. The presence of the esophagus, vertebral
      artery, and other arteries located within the needle path of an SGB at the C6 and
      C7 levels was determined before and during the dislocation maneuver. RESULTS: On
      the left side, the esophagus was located along the needle path in 22 and 39 of 60
      cases at the C6 and C7 levels, respectively, and remained there in 10 and 22 of
      60 cases during dislocation. The esophagus appeared in the needle path during
      dislocation from a previously safe location in 5 and 8 of these cases at the C6
      and C7 locations, respectively. The vertebral artery was located in the needle
      path in a range of 2 to 8 of 60 cases without impact of dislocation on its
      position. Other arteries were located in the needle path in the range of 10 to 17
      of 60 cases with a slight decrease during dislocation. CONCLUSIONS: The esophagus
      and relevant arteries were frequently located in the needle path of conventional
      SGBs. The dislocation maneuver had a partial impact on moving these structures
      away from the target and may increase left-sided esophageal puncture risk in
      certain individuals. Ultrasound (US) imaging is expected to improve the safety of
      SGB, but it will require clinical trials to confirm this expectation.

PMID- 22157740
TI  - Triple-blind randomized clinical trial of time until sensory change using 1.5%
      mepivacaine with epinephrine, 0.5% bupivacaine, or an equal mixture of both for
      infraclavicular block.
AB  - BACKGROUND AND OBJECTIVES: Practitioners mix faster-onset, intermediate-duration
      local anesthetics (LAs) with slower-onset, long-duration LAs to get fast
      peripheral nerve block (PNB) onset and long duration. We hypothesized that 1.5%
      mepivacaine (with epinephrine) (mepivacaine) or 1.5% mepivacaine (with
      epinephrine) mixed with 0.5% bupivacaine (mixed) would reduce PNB sensory onset
      by 20% or more versus 0.5% bupivacaine alone (bupivacaine). METHODS: Patients (n
      = 93) having arm surgery were randomized to 1 of the 3 LA groups. Infraclavicular
      PNB was administered using 1 of 3 LAs; afterward, PNB sensory (motor) onset,
      duration, and other outcomes were assessed. Subjects, physicians, and the
      biostatistician were blinded until study completion. RESULTS: Median
      (interquartile range) PNB sensory onset (in minutes) was as follows: mepivacaine,
      3 (3-6); mixed, 6 (3-6); and bupivacaine, 6 (3-12) (P = 0.0085). Mepivacaine PNB
      sensory onset was not faster than mixed (P = 0.57), but mixed was faster than
      bupivacaine (P = 0.0035). More mixed group patients achieved PNB sensory onset
      (0.81) versus the bupivacaine group (0.54) at 6 mins. Median (interquartile
      range) PNB motor onset (in minutes) was as follows: mepivacaine, 15 (12-18);
      mixed, 17 (12-21); and bupivacaine, 21 (12-24) (P < 0.0001). Median sensory and
      motor PNB duration (in minutes) was as follows: mepivacaine, 281 and 320; mixed,
      439 and 556; and bupivacaine, 850 and 1109. Sensory (motor) PNB duration was
      shorter with mepivacaine versus mixed (P < 0.0001, P = 0.034), and mixed was
      shorter versus bupivacaine (P = 0.0243, P = 0.034). CONCLUSIONS: Mixing 1.5%
      mepivacaine (with epinephrine) with 0.5% bupivacaine speeds up PNB sensory
      (motor) onset compared with 0.5% bupivacaine alone.

PMID- 22157741
TI  - Impact of perioperative pain intensity, pain qualities, and opioid use on chronic
      pain after surgery: a prospective cohort study.
AB  - BACKGROUND AND OBJECTIVES: A better understanding of the pathogenesis of chronic
      postsurgical pain is needed in order to develop effective prevention and
      treatment interventions. The objective of this study was to evaluate the
      incidence and risk factors for chronic postsurgical pain in women undergoing
      gynecologic surgery. METHODS: Pain characteristics, opioid consumption, and
      psychologic factors were captured before and 6 months after surgery. Analyses
      included univariate statistics, relative risks (RRs) and 95% confidence intervals
      (95% CIs), and modified Poisson regression for binary data. RESULTS: Pain and
      pain interference 6 months after surgery was reported by 14% (n = 60/433) and 12%
      (n = 54/433), respectively. Chronic postsurgical pain was reported by 23% (n =
      39/172) with preoperative pelvic pain, 17% (n = 9/54) with preoperative remote
      pain, and 5.1% (n = 10/197) with no preoperative pain. Preoperative state anxiety
      (RR = 1.8; 95% CI, 1.1-2.8), preoperative pain (pelvic RR = 3.7; 95% CI, 1.9-7.2;
      remote RR = 3.0; 95% CI, 1.3-6.9), and moderate/severe in-hospital pain (RR =
      3.0; 95% CI, 1.0-9.4) independently predicted chronic postsurgical pain. The same
      3 factors predicted pain-interference at 6 months. Participants describing
      preoperative pelvic pain as "miserable" and "shooting" were 2.8 (range, 1.3-6.4)
      and 2.1 (range, 1.1-4.0) times more likely to report chronic postsurgical pain,
      respectively. Women taking preoperative opioids were 2.0 (range, 1.2-3.3) times
      more likely to report chronic postsurgical pain than those not taking opioids.
      Women with preoperative pelvic pain who took preoperative opioids were 30% (RR =
      1.3; 95% CI, 0.8-1.9) more likely to report chronic postsurgical pain than those
      with preoperative pelvic pain not taking opioids. CONCLUSIONS: Preoperative pain,
      state anxiety, pain quality descriptors, opioid consumption, and early
      postoperative pain may be important predictors of chronic postsurgical pain,
      which require further investigation.

PMID- 22157742
TI  - Cutaneous analgesia and systemic toxicity of carbetapentane and caramiphen in
      rats.
AB  - BACKGROUND: Caramiphen produces spinal anesthesia; caramiphen and carbetapentane
      have never been tested as infiltrative cutaneous analgesic. The aim of this study
      was to compare cutaneous analgesia of caramiphen and carbetapentane with
      bupivacaine and evaluated their central nervous system and cardiovascular
      toxicity. METHODS: After the blockade of cutaneous trunci muscle reflex with
      subcutaneous drug injections in rats, we evaluated the local anesthetic effect of
      carbetapentane and caramiphen on infiltrative cutaneous analgesia. After
      continuous intravenous infusion of equipotent doses of bupivacaine,
      carbetapentane, caramiphen, and saline, we observed mean arterial blood pressure
      and heart rate and monitored the onset time of seizure, apnea, and impending
      death. RESULTS: Carbetapentane and caramiphen acted like bupivacaine and elicited
      cutaneous analgesia in a dose-related fashion. On a 50% effective dose (ED50)
      basis, the ranks of potencies were bupivacaine (1.78 [1.52-2.07]) >
      carbetapentane (2.53 [2.38-2.77]) > caramiphen (3.60 [3.41-3.99]) (P < 0.01). At
      equianalgesic doses (ED25, ED50, ED75), the duration caused by carbetapentane or
      caramiphen was similar to that caused by bupivacaine. Under equipotent doses, the
      infusion time of carbetapentane or caramiphen required to cause seizure, apnea,
      and impending death was longer than that of bupivacaine (P < 0.05). The decline
      in mean arterial blood pressure and heart rate was slower with carbetapentane or
      caramiphen when compared with bupivacaine (P < 0.01 for the differences) at
      equipotent doses. CONCLUSIONS: Carbetapentane and caramiphen were similar to
      bupivacaine at producing durations of cutaneous analgesia but were less likely
      than bupivacaine to induce central nervous system and cardiovascular systemic
      toxicity.

PMID- 22157743
TI  - ASRA checklist improves trainee performance during a simulated episode of local
      anesthetic systemic toxicity.
AB  - OBJECTIVE: Severe local anesthetic systemic toxicity (LAST) is a rare event, the
      management of which might best be learned using high-fidelity simulation. In its
      2010 Practice Advisory, the American Society of Regional Anesthesia and Pain
      Medicine (ASRA) created a medical checklist to aid in the management of LAST. We
      hypothesized that trainees provided with this checklist would manage a simulated
      episode of LAST more effectively than those without it. A secondary aim of the
      study was to assess the ASRA Checklist's usability and readability. METHODS:
      Trainees undergoing a simulated LAST event were randomized to the checklist group
      (n = 12) or the no-checklist group (n = 13). Our primary outcome was the number
      of medical management tasks completed correctly. Secondary outcomes included
      assessment of the anesthesiologists' nontechnical skills and posttest
      performance. RESULTS: Trainees receiving the checklist demonstrated superior
      medical management of the simulated LAST event: the checklist group correctly
      performed 16.0 (2.6) tasks versus the no-checklist group's 8.8 (3.0) tasks (mean
      [SD], P < 0.001). The checklist group had higher decision making scores on the
      anesthesiologists' nontechnical skills assessment (5.2 [1.8] versus 4.0 [1.35]
      summed rater score, P = 0.037) and had higher knowledge retention 2 months later
      (P = 0.031). Of those trainees randomized to receive the checklist, 7 of 12 used
      it fully (versus partially), which was reflected in higher medical and
      nontechnical performance scores. CONCLUSIONS: Use of the ASRA Checklist
      significantly improved the trainees' medical management and nontechnical
      performance during a simulated episode of severe LAST. Partial use of the
      checklist correlated with lower overall performance.

PMID- 22157744
TI  - Ultrasound-guided obturator nerve block: interfascial injection versus a
      neurostimulation-assisted technique.
AB  - BACKGROUND AND OBJECTIVES: Interfascial injection of local anesthetic under
      ultrasound guidance has been proposed as a new technique for performing an
      obturator nerve block. We hypothesized that interfascial needle placement could
      supplant nerve stimulation as the end point for local anesthetic injection during
      ultrasound-guided obturator nerve block after the division of the obturator
      nerve. METHODS: Fifty spinal anesthesia patients who had experienced unilateral
      adductor muscle spasm during transurethral bladder tumor resection were randomly
      allocated to receive either 5 mL of lidocaine 2% injected under ultrasound
      guidance into the interfascial plane between the adductor longus and the adductor
      brevis and between the adductor brevis and the magnus muscles (US group) or an
      injection of 5 mL of lidocaine 2% in combination with nerve stimulation after
      identification of the divisions of the obturator nerve (USENS group). At 5, 10,
      and 15 minutes after block placement, muscle spasm was assessed by an independent
      observer masked to treatment allocation. The primary outcome was motor block
      onset time. Secondary outcomes were block performance time, total anesthesia
      related time, motor block success at 15 minutes, and number of needle passes.
      RESULTS: Motor block onset time did not differ between the 2 groups (6.2 minutes
      for USENS versus 7.2 minutes for US group, P = 0.225), block performance time was
      longer in the USENS than in the US group (3.0 versus 1.6 minutes, P < 0.001), and
      total anesthesia-related time did not differ between the 2 groups (9.2 versus 8.9
      minutes, P = 0.71). Block success rate at 15 minutes was 100% in the USENS group
      and 88% in the US group (P = 0.23). There was no difference in the number of
      needle passes (2.3 versus 2.1, P = 0.28). CONCLUSIONS: In ultrasound-guided
      obturator nerve block performed after the division of the nerve, injection of
      local anesthetic between the planes of the adductor muscles is comparable to
      nerve stimulation.

PMID- 22157745
TI  - A palmitoylation switch mechanism regulates Rac1 function and membrane
      organization.
AB  - The small GTPase Rac1 plays important roles in many processes, including
      cytoskeletal reorganization, cell migration, cell-cycle progression and gene
      expression. The initiation of Rac1 signalling requires at least two mechanisms:
      GTP loading via the guanosine triphosphate (GTP)/guanosine diphosphate (GDP)
      cycle, and targeting to cholesterol-rich liquid-ordered plasma membrane
      microdomains. Little is known about the molecular mechanisms governing this
      specific compartmentalization. We show that Rac1 can incorporate palmitate at
      cysteine 178 and that this post-translational modification targets Rac1 for
      stabilization at actin cytoskeleton-linked ordered membrane regions.
      Palmitoylation of Rac1 requires its prior prenylation and the intact C-terminal
      polybasic region and is regulated by the triproline-rich motif. Non-palmitoylated
      Rac1 shows decreased GTP loading and lower association with detergent-resistant
      (liquid-ordered) membranes (DRMs). Cells expressing no Rac1 or a palmitoylation
      deficient mutant have an increased content of disordered membrane domains, and
      markers of ordered membranes isolated from Rac1-deficient cells do not correctly
      partition in DRMs. Importantly, cells lacking Rac1 palmitoylation show spreading
      and migration defects. These data identify palmitoylation as a mechanism for Rac1
      function in actin cytoskeleton remodelling by controlling its membrane
      partitioning, which in turn regulates membrane organization.

PMID- 22157746
TI  - CPEB2-eEF2 interaction impedes HIF-1alpha RNA translation.
AB  - Translation of mRNA into protein proceeds in three phases: initiation,
      elongation, and termination. Regulated translation allows the prompt production
      of selective proteins in response to physiological needs and is often controlled
      by sequence-specific RNA-binding proteins that function at initiation. Whether
      the elongation phase of translation can be modulated individually by trans-acting
      factors to synthesize polypeptides at variable rates remains to be determined.
      Here, we demonstrate that the RNA-binding protein, cytoplasmic polyadenylation
      element binding protein (CPEB)2, interacts with the elongation factor, eEF2, to
      reduce eEF2/ribosome-triggered GTP hydrolysis in vitro and slow down peptide
      elongation of CPEB2-bound RNA in vivo. The interaction of CPEB2 with eEF2
      downregulates HIF-1alpha RNA translation under normoxic conditions; however, when
      cells encounter oxidative stress, CPEB2 dissociates from HIF-1alpha RNA, leading
      to rapid synthesis of HIF-1alpha for hypoxic adaptation. This study delineates
      the molecular mechanism of CPEB2-repressed translation and presents a unique
      model for controlling transcript-selective translation at elongation.

PMID- 22157747
TI  - Sec24p and Sec16p cooperate to regulate the GTP cycle of the COPII coat.
AB  - Vesicle budding from the endoplasmic reticulum (ER) employs a cycle of GTP
      binding and hydrolysis to regulate assembly of the COPII coat. We have identified
      a novel mutation (sec24-m11) in the cargo-binding subunit, Sec24p, that
      specifically impacts the GTP-dependent generation of vesicles in vitro. Using a
      high-throughput approach, we defined genetic interactions between sec24-m11 and a
      variety of trafficking components of the early secretory pathway, including the
      candidate COPII regulators, Sed4p and Sec16p. We defined a fragment of Sec16p
      that markedly inhibits the Sec23p- and Sec31p-stimulated GTPase activity of
      Sar1p, and demonstrated that the Sec24p-m11 mutation diminished this inhibitory
      activity, likely by perturbing the interaction of Sec24p with Sec16p. The
      consequence of the heightened GTPase activity when Sec24p-m11 is present is the
      generation of smaller vesicles, leading to accumulation of ER membranes and more
      stable ER exit sites. We propose that association of Sec24p with Sec16p creates a
      novel regulatory complex that retards the GTPase activity of the COPII coat to
      prevent premature vesicle scission, pointing to a fundamental role for GTP
      hydrolysis in vesicle release rather than in coat assembly/disassembly.

PMID- 22157748
TI  - Endocytosis and intracellular trafficking contribute to necrotic
      neurodegeneration in C. elegans.
AB  - Unlike apoptosis, necrotic cell death is characterized by marked loss of plasma
      membrane integrity. Leakage of cytoplasmic material to the extracellular space
      contributes to cell demise, and is the cause of acute inflammatory responses,
      which typically accompany necrosis. The mechanisms underlying plasma membrane
      damage during necrotic cell death are not well understood. We report that
      endocytosis is critically required for the execution of necrosis. Depletion of
      the key endocytic machinery components dynamin, synaptotagmin and endophilin
      suppresses necrotic neurodegeneration induced by diverse genetic and
      environmental insults in C. elegans. We used genetically encoded fluorescent
      markers to monitor the formation and fate of specific types of endosomes during
      cell death in vivo. Strikingly, we find that the number of early and recycling
      endosomes increases sharply and transiently upon initiation of necrosis.
      Endosomes subsequently coalesce around the nucleus and disintegrate during the
      final stage of necrosis. Interfering with kinesin-mediated endosome trafficking
      impedes cell death. Endocytosis synergizes with autophagy and lysosomal
      proteolytic mechanisms to facilitate necrotic neurodegeneration. These findings
      demonstrate a prominent role for endocytosis in cellular destruction during
      neurodegeneration, which is likely conserved in metazoans.

PMID- 22157750
TI  - A call for holistic education scholarship.

PMID- 22157749
TI  - Minor pseudopilin self-assembly primes type II secretion pseudopilus elongation.
AB  - In Gram-negative bacteria, type II secretion systems (T2SS) assemble inner
      membrane proteins of the major pseudopilin PulG (GspG) family into periplasmic
      filaments, which could drive protein secretion in a piston-like manner. Three
      minor pseudopilins PulI, PulJ and PulK are essential for protein secretion in the
      Klebsiella oxytoca T2SS, but their molecular function is unknown. Here, we
      demonstrate that together these proteins prime pseudopilus assembly, without
      actively controlling its length or secretin channel opening. Using molecular
      dynamics, bacterial two-hybrid assays, cysteine crosslinking and functional
      analysis, we show that PulI and PulJ nucleate filament assembly by forming a
      staggered complex in the plasma membrane. Binding of PulK to this complex results
      in its partial extraction from the membrane and in a 1-nm shift between their
      transmembrane segments, equivalent to the major pseudopilin register in the
      assembled PulG filament. This promotes fully efficient pseudopilus assembly and
      protein secretion. Therefore, we propose that PulI, PulJ and PulK self-assembly
      is thermodynamically coupled to the initiation of pseudopilus assembly, possibly
      setting the assembly machinery in motion.

PMID- 22157752
TI  - Structure-function analysis of Nel, a thrombospondin-1-like glycoprotein involved
      in neural development and functions.
AB  - Nel (neural epidermal growth factor (EGF)-like molecule) is a multimeric,
      multimodular extracellular glycoprotein with heparin-binding activity and
      structural similarities to thrombospondin-1. Nel is predominantly expressed in
      the nervous system and has been implicated in neuronal proliferation and
      differentiation, retinal axon guidance, synaptic functions, and spatial learning.
      The Nel protein contains an N-terminal thrombospondin-1 (TSP-N) domain, five
      cysteine-rich domains, and six EGF-like domains. However, little is known about
      the functions of specific domains of the Nel protein. In this study, we have
      performed structure-function analysis of Nel, by using a series of expression
      constructs for different regions of the Nel protein. Our studies demonstrate that
      the TSP-N domain is responsible for homo-multimer formation of Nel and its
      heparin-binding activity. In vivo, Nel and related Nell1 are expressed in several
      regions of the mouse central nervous system with partly overlapping patterns.
      When they are expressed in the same cells in vitro, Nel and Nell1 can form hetero
      multimers through the TSP-N domain, but they do not hetero-oligomerize with
      thrombospondin-1. Whereas both the TSP-N domain and cysteine-rich domains can
      bind to retinal axons in vivo, only the latter causes growth cone collapse in
      cultured retinal axons, suggesting that cysteine-rich domains interact with and
      activate an inhibitory axon guidance receptor. These results suggest that Nel
      interacts with a range of molecules through its different domains and exerts
      distinct functions.

PMID- 22157753
TI  - Regulation of sodium iodide symporter gene expression by Rac1/p38beta mitogen
      activated protein kinase signaling pathway in MCF-7 breast cancer cells.
AB  - Activation of p38 MAPK is a key pathway for cell proliferation and
      differentiation in breast cancer and thyroid cells. The sodium/iodide symporter
      (NIS) concentrates iodide in the thyroid and lactating breast. All-trans-retinoic
      acid (tRA) markedly induces NIS activity in some breast cancer cell lines and
      promotes uptake of beta-emitting radioiodide (131)I sufficient for targeted
      cytotoxicity. To identify a signal transduction pathway that selectively
      stimulates NIS expression, we investigated regulation by the Rac1-p38 signaling
      pathway in MCF-7 breast cancer cells and compared it with regulation in FRTL-5
      rat thyroid cells. Loss of function experiments with pharmacologic inhibitors and
      small interfering RNA, as well as RT-PCR analysis of p38 isoforms, demonstrated
      the requirement of Rac1, MAPK kinase 3B, and p38beta for the full expression of
      NIS in MCF-7 cells. In contrast, p38alpha was critical for NIS expression in FRTL
      5 cells. Treatment with tRA or overexpression of Rac1 induced the phosphorylation
      of p38 isoforms, including p38beta. A dominant negative mutant of Rac1 abolished
      tRA-induced phosphorylation in MCF-7 cells. Overexpression of p38beta or Rac1
      significantly enhanced (1.9- and 3.9-fold, respectively), the tRA-stimulated NIS
      expression in MCF-7 cells. This study demonstrates differential regulation of NIS
      by distinct p38 isoforms in breast cancer cells and thyroid cells. Targeting
      isoform-selective activation of p38 may enhance NIS induction, resulting in
      higher efficacy of (131)I concentration and treatment of breast cancer.

PMID- 22157754
TI  - Structural basis for increased toxicity of pathological abeta42:abeta40 ratios in
      Alzheimer disease.
AB  - The beta-amyloid peptide (Abeta) is directly related to neurotoxicity in
      Alzheimer disease (AD). The two most abundant alloforms of the peptide co-exist
      under normal physiological conditions in the brain in an Abeta(42):Abeta(40)
      ratio of ~1:9. This ratio is often shifted to a higher percentage of Abeta(42) in
      brains of patients with familial AD and this has recently been shown to lead to
      increased synaptotoxicity. The molecular basis for this phenomenon is unclear.
      Although the aggregation characteristics of Abeta(40) and Abeta(42) individually
      are well established, little is known about the properties of mixtures. We have
      explored the biophysical and structural properties of physiologically relevant
      Abeta(42):Abeta(40) ratios by several techniques. We show that Abeta(40) and
      Abeta(42) directly interact as well as modify the behavior of the other. The
      structures of monomeric and fibrillar assemblies formed from Abeta(40) and
      Abeta(42) mixtures do not differ from those formed from either of these peptides
      alone. Instead, the co-assembly of Abeta(40) and Abeta(42) influences the
      aggregation kinetics by altering the pattern of oligomer formation as evidenced
      by a unique combination of solution nuclear magnetic resonance spectroscopy, high
      molecular weight mass spectrometry, and cross-seeding experiments. We relate
      these observations to the observed enhanced toxicity of relevant ratios of
      Abeta(42):Abeta(40) in synaptotoxicity assays and in AD patients.

PMID- 22157755
TI  - BRCA2 protein deficiency exaggerates doxorubicin-induced cardiomyocyte apoptosis
      and cardiac failure.
AB  - The tumor suppressor breast cancer susceptibility gene 2 (BRCA2) plays an
      important role in the repair of DNA damage, and loss of BRCA2 predisposes
      carriers to breast and ovarian cancers. Doxorubicin (DOX) remains the cornerstone
      of chemotherapy in such individuals. However, it is often associated with cardiac
      failure, which once manifests carries a poor prognosis. Because BRCA2 regulates
      genome-wide stability and facilitates DNA damage repair, we hypothesized that
      loss of BRCA2 may increase susceptibility to DOX-induced cardiac failure. To this
      aim, we generated cardiomyocyte-specific BRCA2 knock-out (CM-BRCA2(-/-)) mice
      using the Cre-loxP technology and evaluated their basal and post-DOX treatment
      phenotypes. Although CM-BRCA2(-/-) mice exhibited no basal cardiac phenotype, DOX
      treatment resulted in markedly greater cardiac dysfunction and mortality in CM
      BRCA2(-/-) mice compared with control mice. Apoptosis in left ventricular (LV)
      sections from CM-BRCA2(-/-) mice compared with that in corresponding sections
      from wild-type (WT) littermate controls was also significantly enhanced after DOX
      treatment. Microscopic examination of LV sections from DOX-treated CM-BRCA2(-/-)
      mice revealed a greater number of DNA double-stranded breaks and the absence of
      RAD51 focus formation, an essential marker of double-stranded break repair. The
      levels of p53 and the p53-related proapoptotic proteins p53-up-regulated
      modulator of apoptosis (PUMA) and Bax were significantly increased in samples
      from CM-BRCA2(-/-) mice. This corresponded with increased Bax to Bcl-2 ratios and
      elevated cytochrome c release in the LV sections of DOX-treated CM-BRCA2(-/-)
      mice. Taken together, these data suggest a critical and previously unrecognized
      role of BRCA2 as a gatekeeper of DOX-induced cardiomyocyte apoptosis and
      susceptibility to overt cardiac failure. Pharmacogenomic studies evaluating
      cardiac function in BRCA2 mutation carriers treated with doxorubicin are
      encouraged.

PMID- 22157756
TI  - A nucleotide phosphatase activity in the nucleotide binding domain of an orphan
      resistance protein from rice.
AB  - Plant resistance proteins (R-proteins) are key components of the plant immune
      system activated in response to a plethora of different pathogens. R-proteins are
      P-loop NTPase superfamily members, and current models describe their main
      function as ATPases in defense signaling pathways. Here we show that a subset of
      R-proteins have evolved a new function to combat pathogen infection. This subset
      of R-proteins possesses a nucleotide phosphatase activity in the nucleotide
      binding domain. Related R-proteins that fall in the same phylogenetic clade all
      show the same nucleotide phosphatase activity indicating a conserved function
      within at least a subset of R-proteins. R-protein nucleotide phosphatases
      catalyze the production of nucleoside from nucleotide with the nucleotide
      monophosphate as the preferred substrate. Mutation of conserved catalytic
      residues substantially reduced activity consistent with the biochemistry of P
      loop NTPases. Kinetic analysis, analytical gel filtration, and chemical cross
      linking demonstrated that the nucleotide-binding domain was active as a multimer.
      Nuclear magnetic resonance and nucleotide analogues identified the terminal
      phosphate bond as the target of a reaction that utilized a metal-mediated
      nucleophilic attack by water on the phosphoester. In conclusion, we have
      identified a group of R-proteins with a unique function. This biochemical
      activity appears to have co-evolved with plants in signaling pathways designed to
      resist pathogen attack.

PMID- 22157757
TI  - Transient receptor potential channel 1 (TRPC1) reduces calcium permeability in
      heteromeric channel complexes.
AB  - Specific biological roles of the classical transient receptor potential channel 1
      (TRPC1) are still largely elusive. To investigate the function of TRPC1 proteins
      in cell physiology, we studied heterologously expressed TRPC1 channels and found
      that recombinant TRPC1 subunits do not form functional homomeric channels.
      Instead, by electrophysiological analysis TRPC1 was shown to form functional
      heteromeric, receptor-operated channel complexes with TRPC3, -4, -5, -6, and -7
      indicating that TRPC1 proteins can co-assemble with all members of the TRPC
      subfamily. In all TRPC1-containing heteromers, TRPC1 subunits significantly
      decreased calcium permeation. The exchange of select amino acids in the putative
      pore-forming region of TRPC1 further reduced calcium permeability, suggesting
      that TRPC1 subunits contribute to the channel pore. In immortalized immature
      gonadotropin-releasing hormone neurons endogenously expressing TRPC1, -2, -5, and
      -6, down-regulation of TRPC1 resulted in increased calcium permeability and
      elevated basal cytosolic calcium concentrations. We did not observe any
      involvement of TRPC1 in store-operated cation influx. Notably, TRPC1 suppressed
      the migration of gonadotropin-releasing hormone neurons without affecting cell
      proliferation. Conversely, in TRPC1 knockdown neurons, specific migratory
      properties like distance covered, locomotion speed, and directionality were
      increased. These findings suggest a novel regulatory mechanism relying on the
      expression of TRPC1 and the subsequent formation of heteromeric TRPC channel
      complexes with reduced calcium permeability, thereby fine-tuning neuronal
      migration.

PMID- 22157758
TI  - Giant DNA virus mimivirus encodes pathway for biosynthesis of unusual sugar 4
      amino-4,6-dideoxy-D-glucose (Viosamine).
AB  - Mimivirus is one the largest DNA virus identified so far, infecting several
      Acanthamoeba species. Analysis of its genome revealed the presence of a nine-gene
      cluster containing genes potentially involved in glycan formation. All of these
      genes are co-expressed at late stages of infection, suggesting their role in the
      formation of the long fibers covering the viral surface. Among them, we
      identified the L136 gene as a pyridoxal phosphate-dependent sugar
      aminotransferase. This enzyme was shown to catalyze the formation of UDP-4-amino
      4,6-dideoxy-D-glucose (UDP-viosamine) from UDP-4-keto-6-deoxy-D-glucose, a key
      compound involved also in the biosynthesis of L-rhamnose. This finding further
      supports the hypothesis that Mimivirus encodes a glycosylation system that is
      completely independent of the amoebal host. Viosamine, together with rhamnose, (N
      acetyl)glucosamine, and glucose, was found as a major component of the viral
      glycans. Most of the sugars were associated with the fibers, confirming a
      capsular-like nature of the viral surface. Phylogenetic analysis clearly
      indicated that L136 was not a recent acquisition from bacteria through horizontal
      gene transfer, but it was acquired very early during evolution. Implications for
      the origin of the glycosylation machinery in giant DNA virus are also discussed.

PMID- 22157759
TI  - Regulation of the ligand-dependent activation of the epidermal growth factor
      receptor by calmodulin.
AB  - Calmodulin (CaM) is the major component of calcium signaling pathways mediating
      the action of various effectors. Transient increases in the intracellular calcium
      level triggered by a variety of stimuli lead to the formation of Ca(2+)/CaM
      complexes, which interact with and activate target proteins. In the present study
      the role of Ca(2+)/CaM in the regulation of the ligand-dependent activation of
      the epidermal growth factor receptor (EGFR) has been examined in living cells. We
      show that addition of different cell permeable CaM antagonists to cultured cells
      or loading cells with a Ca(2+) chelator inhibited ligand-dependent EGFR
      auto(trans)phosphorylation. This occurred also in the presence of inhibitors of
      protein kinase C, CaM-dependent protein kinase II and calcineurin, which are
      known Ca(2+)- and/or Ca(2+)/CaM-dependent EGFR regulators, pointing to a direct
      effect of Ca(2+)/CaM on the receptor. Furthermore, we demonstrate that down
      regulation of CaM in conditional CaM knock out cells stably transfected with the
      human EGFR decreased its ligand-dependent phosphorylation. Substitution of six
      basic amino acid residues within the CaM-binding domain (CaM-BD) of the EGFR by
      alanine resulted in a decreased phosphorylation of the receptor and of its
      downstream substrate phospholipase Cgamma1. These results support the hypothesis
      that Ca(2+)/CaM regulates the EGFR activity by directly interacting with the CaM
      BD of the receptor located at its cytosolic juxtamembrane region.

PMID- 22157760
TI  - Iron-responsive transcription factor Aft1 interacts with kinetochore protein Iml3
      and promotes pericentromeric cohesin.
AB  - The Saccharomyces cerevisiae iron-responsive transcription factor, Aft1, has a
      well established role in regulating iron homeostasis through the transcriptional
      induction of iron-regulon genes. However, recent studies have implicated Aft1 in
      other cellular processes independent of iron regulation such as chromosome
      stability. In addition, chromosome spreads and two-hybrid data suggest that Aft1
      interacts with and co-localizes with kinetochore proteins; however, the cellular
      implications of this have not been established. Here, we demonstrate that Aft1
      associates with the kinetochore complex through Iml3. Furthermore, like Iml3,
      Aft1 is required for the increased association of cohesin with pericentric
      chromatin, which is required to resist microtubule tension, and aft1Delta cells
      display chromosome segregation defects in meiosis. Our work defines a new role
      for Aft1 in chromosome stability and transmission.

PMID- 22157761
TI  - Inhibition of signal transducer and activator of transcription 3 (STAT3)
      attenuates interleukin-6 (IL-6)-induced collagen synthesis and resultant
      hypertrophy in rat heart.
AB  - IL-6 has been shown to play a major role in collagen up-regulation process during
      cardiac hypertrophy, although the precise mechanism is still not known. In this
      study we have analyzed the mechanism by which IL-6 modulates cardiac hypertrophy.
      For the in vitro model, IL-6-treated cultured cardiac fibroblasts were used,
      whereas the in vivo cardiac hypertrophy model was generated by renal artery
      ligation in adult male Wistar rats (Rattus norvegicus). During induction of
      hypertrophy, increased phosphorylation of STAT1, STAT3, MAPK, and ERK proteins
      was observed both in vitro and in vivo. Treatment of fibroblasts with specific
      inhibitors for STAT1 (fludarabine, 50 MUM), STAT3 (S31-201, 10 MUM), p38 MAPK
      (SB203580, 10 MUM), and ERK1/2 (U0126, 10 MUM) resulted in down-regulation of IL
      6-induced phosphorylation of specific proteins; however, only S31-201 and
      SB203580 inhibited collagen biosynthesis. In ligated rats in vivo, only STAT3
      inhibitors resulted in significant decrease in collagen synthesis and hypertrophy
      markers such as atrial natriuretic factor and beta-myosin heavy chain. In
      addition, decreased heart weight to body weight ratio and improved cardiac
      function as measured by echocardiography was evident in animals treated with
      STAT3 inhibitor or siRNA. Compared with IL-6 neutralization, more pronounced down
      regulation of collagen synthesis and regression of hypertrophy was observed with
      STAT3 inhibition, suggesting that STAT3 is the major downstream signaling
      molecule and a potential therapeutic target for cardiac hypertrophy.

PMID- 22157762
TI  - Mitochondrial Rac1 GTPase import and electron transfer from cytochrome c are
      required for pulmonary fibrosis.
AB  - The generation of reactive oxygen species, particularly H(2)O(2), from alveolar
      macrophages is causally related to the development of pulmonary fibrosis. Rac1, a
      small GTPase, is known to increase mitochondrial H(2)O(2) generation in
      macrophages; however, the mechanism by which this occurs is not known. This study
      shows that Rac1 is localized in the mitochondria of alveolar macrophages from
      asbestosis patients, and mitochondrial import requires the C-terminal cysteine of
      Rac1 (Cys-189), which is post-translationally modified by geranylgeranylation.
      Furthermore, H(2)O(2) generation mediated by mitochondrial Rac1 requires electron
      transfer from cytochrome c to a cysteine residue on Rac1 (Cys-178). Asbestos
      exposed mice harboring a conditional deletion of Rac1 in macrophages demonstrated
      decreased oxidative stress and were significantly protected from developing
      pulmonary fibrosis. These observations demonstrate that mitochondrial import and
      direct electron transfer from cytochrome c to Rac1 modulates mitochondrial
      H(2)O(2) production in alveolar macrophages pulmonary fibrosis.

PMID- 22157763
TI  - Peracetylated N-acetylmannosamine, a synthetic sugar molecule, efficiently
      rescues muscle phenotype and biochemical defects in mouse model of sialic acid
      deficient myopathy.
AB  - Distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy
      (DMRV/hIBM), characterized by progressive muscle atrophy, weakness, and
      degeneration, is due to mutations in GNE, a gene encoding a bifunctional enzyme
      critical in sialic acid biosynthesis. In the DMRV/hIBM mouse model, which
      exhibits hyposialylation in various tissues in addition to muscle atrophy,
      weakness, and degeneration, we recently have demonstrated that the myopathic
      phenotype was prevented by oral administration of N-acetylneuraminic acid, N
      acetylmannosamine, and sialyllactose, underscoring the crucial role of
      hyposialylation in the disease pathomechanism. The choice for the preferred
      molecule, however, was limited probably by the complex pharmacokinetics of sialic
      acids and the lack of biomarkers that could clearly show dose response. To
      address these issues, we screened several synthetic sugar compounds that could
      increase sialylation more remarkably and allow demonstration of measurable
      effects in the DMRV/hIBM mice. In this study, we found that tetra-O-acetylated N
      acetylmannosamine increased cell sialylation most efficiently, and in vivo
      evaluation in DMRV/hIBM mice revealed a more dramatic, measurable effect and
      improvement in muscle phenotype, enabling us to establish analysis of protein
      biomarkers that can be used for assessing response to treatment. Our results
      provide a proof of concept in sialic acid-related molecular therapy with
      synthetic monosaccharides.

PMID- 22157764
TI  - The enzymatic activity of lysyl oxidas-like-2 (LOXL2) is not required for LOXL2
      induced inhibition of keratinocyte differentiation.
AB  - Lysyl oxidase-like-2 (LOXL2) induces tumor progression and fibrosis. It also
      inhibits the differentiation of keratinocytes promoting development of squamous
      cell carcinomas. Stimulation of HaCaT skin keratinocytes with exogenous LOXL2 or
      overexpression of LOXL2 in these cells inhibits their differentiation as
      manifested by inhibition of calcium or vitamin D-induced involucrin expression.
      The inhibition was abrogated by the LOXL2 function-blocking monoclonal antibody
      AB0023 as well as by an anti-LOXL2 polyclonal antibody. Surprisingly, a point
      mutated form of LOXL2 (LOXL2(Y689F)) lacking enzymatic activity, as well as a
      LOXL2 deletion mutant lacking the entire catalytic domain, also inhibited calcium
      or vitamin D-induced up-regulation of involucrin expression, suggesting that the
      enzymatic activity of LOXL2 is not required for this activity. This conclusion
      was supported by experiments that showed that beta-aminoproprionitrile, an
      irreversible competitive inhibitor of the enzymatic activity of all lysyl
      oxidases, is unable to abolish the LOXL2-induced inhibition of HaCaT cell
      differentiation. The activity of LOXL2(Y689F) required the presence of the fourth
      scavenger receptor-cysteine-rich (SRCR) domain of LOXL2, which is also the
      binding target of AB0023. Epitope-tagged LOXL2(Y689F) was internalized at 37 
      degrees C by HaCaT cells. The internalization was inhibited by AB0023 and by
      competition with unlabeled LOXL2, suggesting that these cells may express a LOXL2
      receptor. Our results suggest that agents that inhibit the enzymatic activity of
      LOXL2 may not suffice to inhibit completely the effects of LOXL2 on complex
      processes that involve altered states of cellular differentiation.

PMID- 22157765
TI  - MicroRNA-30a sensitizes tumor cells to cis-platinum via suppressing beclin 1
      mediated autophagy.
AB  - Autophagy is activated in cancer cells during chemotherapy and often contributes
      to tumor chemotherapy resistance. In this study, we characterized the role of
      microRNA-30a (miR-30a) in the coordination of cancer cell apoptosis and
      autophagy, which determines the sensitivity of cancer cells to chemotherapy.
      First, the autophagy activity in cancer cells increased after cis-dichloro
      diamine platinum (cis-DDP) or Taxol treatment, as indicated by the enhanced
      expression of beclin 1, a key regulator of autophagy, and increased number of LC3
      positive autophagosomes. Second, miRNA screening using a TaqMan probe-based
      quantitative RT-PCR assay identified that miR-30a, a miRNA that targets beclin 1,
      was significantly reduced in tumor cells by cis-DDP treatment. Forced expression
      of miR-30a significantly reduced beclin 1 and the autophagy activity of tumor
      cells induced by cis-DDP. Third, the blockade of tumor cell autophagy activity by
      miR-30a expression or 3-methyladenine significantly increased tumor cell
      apoptosis induced by cis-DDP treatment. Finally, an in vivo tumor implantation
      mouse model clearly showed that elevation of miR-30a in implanted tumor cells by
      administration of the recombinant lentivirus expressing miR-30a strongly enhanced
      cis-DDP-induced apoptosis of tumor cells. In conclusion, our results demonstrate
      for the first time that miR-30a can sensitize tumor cells to cis-DDP via reducing
      beclin 1-mediated autophagy and that increasing miR-30a level in tumor cells
      represents a novel approach to enhance the efficacy of chemotherapy during cancer
      treatment.

PMID- 22157766
TI  - NADPH oxidase is internalized by clathrin-coated pits and localizes to a Rab27A/B
      GTPase-regulated secretory compartment in activated macrophages.
AB  - Here, we report that activation of different types of tissue macrophages,
      including microglia, by lipopolysaccharide (LPS) or GM-CSF stimulation correlates
      with the quantitative redistribution of NADPH oxidase (cyt b(558)) from the
      plasma membrane to an intracellular stimulus-responsive storage compartment. Cryo
      immunogold labeling of gp91(phox) and CeCl(3) cytochemistry showed the presence
      of gp91(phox) and oxidant production in numerous small (<100 nm) vesicles. Cell
      homogenization and sucrose gradient centrifugation in combination with
      transferrin-HRP/DAB ablation showed that more than half of cyt b(558) is present
      in fractions devoid of endosomal markers, which is supported by morphological
      evidence to show that the cyt b(558)-containing compartment is distinct from
      endosomes or biosynthetic organelles. Streptolysin-O-mediated guanosine 5'-3-O
      (thio)triphosphate loading of Ra2 microglia caused exocytosis of a major
      complement of cyt b(558) under conditions where lysosomes or endosomes were not
      mobilized. We establish phagocytic particles and soluble mediators ATP, TNFalpha,
      and CD40L as physiological inducers of cyt b(558) exocytosis to the cell surface,
      and by shRNA knockdown, we identify Rab27A/B as positive or negative regulators
      of vesicular mobilization to the phagosome or the cell surface, respectively.
      Exocytosis was followed by clathrin-dependent internalization of cyt b(558),
      which could be blocked by a dominant negative mutant of the clathrin-coated pit
      associated protein Eps15. Re-internalized cyt b(558) did not reach lysosomes but
      associated with recycling endosomes and undefined vesicular elements. In
      conclusion, cyt b(558) depends on clathrin for internalization, and in activated
      macrophages NADPH oxidase occupies a Rab27A/B-regulated secretory compartment,
      which allows rapid agonist-induced redistribution of superoxide production in the
      cell.

PMID- 22157767
TI  - Unique peptide substrate binding properties of 110-kDa heat-shock protein
      (Hsp110) determine its distinct chaperone activity.
AB  - The molecular chaperone 70-kDa heat-shock proteins (Hsp70s) play essential roles
      in maintaining protein homeostasis. Hsp110, an Hsp70 homolog, is highly efficient
      in preventing protein aggregation but lacks the hallmark folding activity seen in
      Hsp70s. To understand the mechanistic differences between these two chaperones,
      we first characterized the distinct peptide substrate binding properties of
      Hsp110s. In contrast to Hsp70s, Hsp110s prefer aromatic residues in their
      substrates, and the substrate binding and release exhibit remarkably fast
      kinetics. Sequence and structure comparison revealed significant differences in
      the two peptide-binding loops: the length and properties are switched. When we
      swapped these two loops in an Hsp70, the peptide binding properties of this
      mutant Hsp70 were converted to Hsp110-like, and more impressively, it
      functionally behaved like an Hsp110. Thus, the peptide substrate binding
      properties implemented in the peptide-binding loops may determine the chaperone
      activity differences between Hsp70s and Hsp110s.

PMID- 22157768
TI  - Efficacy of pegylated interferon alfa-2a or alfa-2b in combination with ribavirin
      in the treatment of chronic hepatitis caused by hepatitis C virus genotype 1b.
AB  - INTRODUCTION: Treatment of chronic hepatitis C (CHC) with pegylated interferon
      (Peg-IFN) and ribavirin leads to sustained virological response (SVR) in
      approximately 50% of the patients. SVR depends on hepatitis C virus (HCV) and
      host factors, including IL28B genotypes. OBJECTIVES: The aim of the study was to
      investigate the therapeutic efficacy of the difficult-to-treat HCV genotype 1b in
      patients from the south of Poland. PATIENTS AND METHODS: A total of 260 adult
      patients with CHC and HCV genotype 1b were treated with Peg-IFN alfa-2a or Peg
      IFN alfa-2b with ribavirin for 48 weeks. Efficacy was assessed at 12 weeks (early
      virological response - EVR), 48 weeks (end-of-treatment response - ETR), and at 6
      months (SVR). HCV-RNA, alanine transaminase (ALT), and other biochemical
      parameters were measured in serum at baseline and at 12, 48, and 72 weeks of
      therapy. RESULTS: HCV-RNA levels were 3.72 +/-1.17 * 106 IU/ml at baseline and
      decreased significantly at 12 weeks (0.02 +/-0.17 * 106 IU/ml); there were no
      differences between the group treated with Peg-INF alfa-2a and the group treated
      with Peg-INF alfa-2b. ALT was 94.1 +/-7.6 IU/l at baseline and decreased
      significantly at 12 weeks (42.5 +/-3.1 IU/l). The overall EVR, ETR, and SVR were
      achieved by 63.9%, 77.7%, and 48.1% of the patients, respectively. Tolerance of
      therapy was similar in both groups. CONCLUSIONS: Efficacy of Peg-IFN alfa-2a with
      ribavirin is not significantly different from that of Peg-IFN alfa-2b with
      ribavirin, and SVR was achieved in 48.3% and 44.3% of the patients, respectively.
      Our study confirms that the efficacy of treatment of patients with HCV genotype
      1b from the southern region of Poland is similar to that observed in the overall
      Polish population.

PMID- 22157769
TI  - Assessment of physical activity using wearable monitors:  recommendations for
      monitor calibration and use in the field.
AB  - This article provides recommendations for the use of wearable monitors for
      assessing physical activity. We have provided recommendations for measurement
      researchers, end users, and developers of activity monitors. We discuss new
      horizons and future directions in the field of objective measurement of physical
      activity and present challenges that remain for the future. These recommendations
      are based on the proceedings from the workshop "Objective Measurement of Physical
      Activity: Best Practices and Future Direction," held on July 20-21, 2009, and
      also on data and information presented since the workshop.

PMID- 22157770
TI  - Redefining the roles of sensors in objective physical activity monitoring.
AB  - BACKGROUND: Because physical activity researchers are increasingly using
      objective portable devices, this review describes the current state of the
      technology to assess physical activity, with a focus on specific sensors and
      sensor properties currently used in monitors and their strengths and weaknesses.
      Additional sensors and sensor properties desirable for activity measurement and
      best practices for users and developers also are discussed. BEST PRACTICES: We
      grouped current sensors into three broad categories for objectively measuring
      physical activity: associated body movement, physiology, and context. Desirable
      sensor properties for measuring physical activity and the importance of these
      properties in relationship to specific applications are addressed, and the
      specific roles of transducers and data acquisition systems within the monitoring
      devices are defined. Technical advancements in sensors, microcomputer processors,
      memory storage, batteries, wireless communication, and digital filters have made
      monitors more usable for subjects (smaller, more stable, and longer running time)
      and for researchers (less costly, higher time resolution and memory storage,
      shorter download time, and user-defined data features). FUTURE DIRECTIONS: Users
      and developers of physical activity monitors should learn about the basic
      properties of their sensors, such as range, accuracy, and precision, while
      considering the data acquisition/filtering steps that may be critical to data
      quality and may influence the desirable measurement outcome(s).

PMID- 22157771
TI  - New horizons in sensor development.
AB  - BACKGROUND: Accelerometry and other sensing technologies are important tools for
      physical activity measurement. Engineering advances have allowed developers to
      transform clunky, uncomfortable, and conspicuous monitors into relatively small,
      ergonomic, and convenient research tools. New devices can be used to collect data
      on overall physical activity and, in some cases, posture, physiological state,
      and location, for many days or weeks from subjects during their everyday lives.
      In this review article, we identify emerging trends in several types of
      monitoring technologies and gaps in the current state of knowledge. BEST
      PRACTICES: The only certainty about the future of activity-sensing technologies
      is that researchers must anticipate and plan for change. We propose a set of best
      practices that may accelerate adoption of new devices and increase the likelihood
      that data being collected and used today will be compatible with new data sets
      and methods likely to appear on the horizon. FUTURE DIRECTIONS: We describe
      several technology-driven trends, ranging from continued miniaturization of
      devices that provide gross summary information about activity levels and energy
      expenditure to new devices that provide highly detailed information about the
      specific type, amount, and location of physical activity. Some devices will take
      advantage of consumer technologies, such as mobile phones, to detect and respond
      to physical activity in real time, creating new opportunities in measurement,
      remote compliance monitoring, data-driven discovery, and intervention.

PMID- 22157772
TI  - Calibration and validation of wearable monitors.
AB  - BACKGROUND: Wearable monitors are increasingly being used to objectively monitor
      physical activity in research studies within the field of exercise science.
      Calibration and validation of these devices are vital to obtaining accurate data.
      This article is aimed primarily at the physical activity measurement specialist,
      although the end user who is conducting studies with these devices also may
      benefit from knowing about this topic. BEST PRACTICES: Initially, wearable
      physical activity monitors should undergo unit calibration to ensure
      interinstrument reliability. The next step is to simultaneously collect both raw
      signal data (e.g., acceleration) from the wearable monitors and rates of energy
      expenditure, so that algorithms can be developed to convert the direct signals
      into energy expenditure. This process should use multiple wearable monitors and a
      large and diverse subject group and should include a wide range of physical
      activities commonly performed in daily life (from sedentary to vigorous). FUTURE
      DIRECTIONS: New methods of calibration now use "pattern recognition" approaches
      to train the algorithms on various activities, and they provide estimates of
      energy expenditure that are much better than those previously available with the
      single-regression approach. Once a method of predicting energy expenditure has
      been established, the next step is to examine its predictive accuracy by cross
      validating it in other populations. In this article, we attempt to summarize the
      best practices for calibration and validation of wearable physical activity
      monitors. Finally, we conclude with some ideas for future research ideas that
      will move the field of physical activity measurement forward.

PMID- 22157773
TI  - Protocols for evaluating equivalency of accelerometry-based activity monitors.
AB  - A wide array of accelerometer-based activity monitors has been developed to
      facilitate objective monitoring of physical activity behaviors, but it has proven
      difficult to equate outputs from different monitors. On the surface, commercially
      available monitors seem to be performing the same basic task-monitoring total
      body acceleration. However, differences in sensor properties and internal data
      processing have made it difficult to directly compare output from different
      monitors. In recent years, many new competing technologies have been released
      into the market, compounding the challenge of evaluating monitor equivalency and
      the relative strengths and limitations of different monitors. To advance physical
      activity assessment and improve our ability to compare results across studies
      using different monitors, it is important to conduct functional equivalency
      studies in a standardized and systematic way. This article summarizes issues
      associated with monitor equivalency and proposes methods for standardization and
      quality control in future research.

PMID- 22157774
TI  - Assessing physical activity using wearable monitors:  measures of physical
      activity.
AB  - BACKGROUND: Physical activity may be defined broadly as "all bodily actions
      produced by the contraction of skeletal muscle that increase energy expenditure
      above basal level." Physical activity is a complex construct that can be
      classified into major categories qualitatively, quantitatively, or contextually.
      The quantitative assessment of physical activity using wearable monitors is
      grounded in the measurement of energy expenditure. Six main categories of
      wearable monitors are currently available to investigators: pedometers, load
      transducers/foot-contact monitors, accelerometers, HR monitors, combined
      accelerometer and HR monitors, and multiple sensor systems. BEST PRACTICES:
      Currently available monitors are capable of measuring total physical activity as
      well as components of physical activity that play important roles in human
      health. The selection of wearable monitors for measuring physical activity will
      depend on the physical activity component of interest, study objectives,
      characteristics of the target population, and study feasibility in terms of cost
      and logistics. FUTURE DIRECTIONS: Future development of sensors and analytical
      techniques for assessing physical activity should focus on the dynamic ranges of
      sensors, comparability for sensor output across manufacturers, and the
      application of advanced modeling techniques to predict energy expenditure and
      classify physical activities. New approaches for qualitatively classifying
      physical activity should be validated using direct observation or recording. New
      sensors and methods for quantitatively assessing physical activity should be
      validated in laboratory and free-living populations using criterion methods of
      calorimetry or doubly labeled water.

PMID- 22157775
TI  - Modeling physical activity outcomes from wearable monitors.
AB  - Although the measurement of physical activity with wearable monitors may be
      considered objective, consensus guidelines for collecting and processing these
      objective data are lacking. This article presents an algorithm embodying best
      practice recommendations for collecting, processing, and reporting physical
      activity data routinely collected with accelerometry-based activity monitors.
      This algorithm is proposed as a linear series of seven steps within three
      successive phases. The Precollection Phase includes two steps. Step 1 defines the
      population of interest, the type and intensity of physical activity behaviors to
      be targeted, and the preferred outcome variables, and identifies the epoch
      duration. In Step 2, the activity monitor is selected, and decisions about how
      long and where on the body the monitor is to be worn are made. The Data
      Collection Phase, Step 3, consists of collecting and processing activity monitor
      data and is dependent on decisions made previously. The Postcollection Phase
      consists of four steps. Step 4 involves quality and quantity control checks of
      the activity monitor data. In Step 5, the raw data are transformed into
      physiologically meaningful units using a calibration algorithm. Step 6 involves
      summarizing these data according to the target behavior. In Step 7, physical
      activity outcome variables based on time, energy expenditure, or movement type
      are generated. Best practice recommendations include the full disclosure of each
      step within the algorithm when reporting monitor-derived physical activity
      outcome variables in the research literature. As such, those reading and
      publishing within the research literature, as well as future users, will have the
      best chance for understanding the interactions between study methodology and
      activity monitor selection, as well as the best possibility for relating their
      own monitor-derived physical activity outcome variables to the research
      literature.

PMID- 22157776
TI  - Statistical considerations in the analysis of accelerometry-based activity
      monitor data.
AB  - We review and discuss three statistical aspects of accelerometer-based estimates
      of physical activity energy expenditure (PAEE):1) the nature of the relationship
      between accelerometer output and PAEE;2) statistical aspects of calibration
      studies; and 3) two specialized statistical methods that are applicable to the
      problem of measurement error modeling and missing data methods.We call for a
      continuing development of statistical methods that use more characteristics of
      the accelerometer signal to estimate PAEE, advocate the use of bias and SE
      statistics and inclusion of cross-validation in accelerometer research designs,
      and encourage more efforts to understand systematic and random errors in
      accelerometer-based estimates of PAEE.

PMID- 22157777
TI  - Best practices for using physical activity monitors in population-based research.
AB  - The use of physical activity monitors in population-based research has increased
      dramatically in the past decade. In this report, we review the major purpose for
      using physical activity monitors in different types of population-based studies
      (i.e., surveillance, intervention, association studies) and discuss the strengths
      and weaknesses for the various behavioral outcomes derived from monitors for each
      study type. We also update and extend previous recommendations for use of these
      instruments in large-scale studies, particularly with respect to selecting
      monitor systems in the context of technological advances that have occurred in
      recent years. The current state of the science with respect to optimal
      measurement schedules for use of physical activity monitors is also discussed. A
      checklist and flowchart are provided so that investigators have more guidance
      when reporting key elements of monitor use in their studies.

PMID- 22157780
TI  - From the editor.

PMID- 22157778
TI  - Accelerometer use with children, older adults, and adults with functional
      limitations.
AB  - Accurately assessing physical activity behavior in children, older adults, and
      adults with functional limitations is essential to further our understanding of
      determinants of physical activity behavior in these populations and to design,
      implement, and evaluate interventions designed to increase physical activity
      participation. Objective methods to assess physical activity behavior, owing to
      improvements in accuracy and precision over self-report measures, have become
      common in research and practice settings. This article reviews the current use of
      objective methods to assess physical activity in observational, determinant, and
      intervention studies for children, older adults, and adults with functional
      limitations. Important considerations are presented when adopting prediction
      algorithms developed on one population, and using in another population that is
      markedly different in age, health, and functional status. Best practices are
      presented, along with future recommendations for research to advance this area of
      scientific inquiry.

PMID- 22157779
TI  - ActiGraph and Actical physical activity monitors: a peek under the hood.
AB  - Since the 1980s, accelerometer-based activity monitors have been used by
      researchers to quantify physical activity. The technology of these monitors has
      continuously evolved. For example, changes have been made to monitor hardware
      (type of sensor (e.g., piezoelectric, piezoresistive, capacitive)) and output
      format (counts vs raw signal). Commonly used activity monitors belong to the
      ActiGraph and the Actical families. This article presents information on several
      electromechanical aspects of these commonly used activity monitors. The majority
      of the article focuses on the evolution of the ActiGraph activity monitor by
      describing the differences among the 7164, the GT1M, and the GT3X models. This is
      followed by brief descriptions of the influences of device firmware and monitor
      calibration status. We also describe the Actical, but the discussion is short
      because this device has not undergone any major changes since it was first
      introduced. This article may help researchers gain a better understanding of the
      functioning of activity monitors. For example, a common misconception among
      physical activity researchers is that the ActiGraph GT1M and GT3X are
      piezoelectric sensor-based monitors. Thus, this information may also help
      researchers to describe these monitors more accurately in scientific
      publications.

PMID- 22157781
TI  - Guest editorial.

PMID- 22157782
TI  - Guest editorial.

PMID- 22157783
TI  - Nurses in the C-suite: leadership beyond chief nurse.
AB  - The US health care system is reaching a critical point. Consistent cost increases
      coupled with a struggling economy has illuminated the burden of more than $650
      billion annually in health care expenditures. The ability to afford health care
      is a growing concern for individuals, businesses, and state and federal
      governments. In addition to costs, variability in quality, and utilization belie
      any claims of a rational and consistent system of care. Transformational change
      will require leaders to shape our future health care institutions. Nursing has
      historically not been considered as a leadership source for change of this
      magnitude. However, due to the sheer size of nursing, core skills, and
      competencies, nurses could be a viable resource. Competencies needed for nurse,
      health care, and physician executives were compared using the HealthCare
      Leadership Alliance data, which created a body of knowledge that identifies
      competencies in 5 domains. Findings demonstrate that nurses, health care
      executives, and physicians possess more than 80% of the competencies reviewed. To
      successfully take on the role of leading institutional response to the
      dramatically changing health care environment, nurses must not only have the
      requisite leadership skills and experience, they must also have an expectation of
      themselves to lead at this level.

PMID- 22157784
TI  - Transforming nursing leadership roles: from CNO to CEO.
AB  - Future chief executive officers (CEOs) in health care may very well be required
      to have clinical backgrounds. Nurses are in an excellent position to lead
      hospitals and health care systems through impending sea changes. Moving from the
      chief nursing officer to the CEO requires core leadership competencies and a
      framework to ensure success. This framework needs to include a self-assessment
      and a personal development plan. Lessons learned offered to aspiring CEOs include
      insights and tools to make getting to the top achievable.

PMID- 22157785
TI  - Nursing leadership... from the board room to the bedside.
AB  - Nurses running hospitals is not new. Florence Nightingale could be considered the
      first hospital administrator. What is changing is the growth of RN chief
      executive officers (CEOs), from 10% in 2004 to 18% in 2010. Furthermore, nearly
      20% of chief nursing officers (CNOs) aspire to be CEOs. Is this a natural growth
      of CNO to vice president of patient care services to chief operating officer...to
      RN CEO? The research on RN CEOs is very small. Therefore, the author set out to
      obtain a journalistic snapshot of Arizona's 12 hospital RN CEOs through
      interviews. Of the 12, 3 were corporate CEOs at the system level, they saw over
      several hospitals, and 9 were CEOs over 1 to 2 hospitals. This article discusses
      some of the finding from these interviews.

PMID- 22157786
TI  - A nurse's rise to CEO: a conversation with St. Luke's-Roosevelt Hospital Center's
      Frank J. Cracolici.

PMID- 22157787
TI  - A journey of leadership: from bedside nurse to chief executive officer.
AB  - Understanding leadership from the inside out was a journey that spanned a 40-year
      career in health care. This article describes an individual's journey of becoming
      an effective executive leader using the LEADS in a caring environment-
      capabilities framework. This framework was recently developed in Canada and is
      now used broadly to understand the complexity and depth of health care leadership
      skills and challenges. The author utilizes the framework to explore leadership
      skill development from a personal perspective to a broader system transformation
      level. Challenges and successes along this journey are included to highlight the
      manner in which leadership evolves with experience, time, and determination. A
      retrospective view of a successful career in health care provides the model for
      others to consider a similar career path using a theoretical base and a
      thoughtful process of personal development.

PMID- 22157788
TI  - Making the transition: an interview with nurse chief executive officers at
      Catholic Health Initiatives.
AB  - Nurses have long been leaders in health care, and many possess the skills and
      talents not only to provide superior patient care but also to lead institutions
      as chief executive officers (CEO). It is not surprising that nurses are moving
      into the role of CEOs in their organizations. Some nurses have purposefully
      obtained MHA or MBA graduate degrees to pursue administrative careers. Others
      have advanced to top organizational positions of leadership with non-business
      related graduate degrees. This article interviews 6 such professionals to
      understand their journey to becoming CEO/president of their organization.

PMID- 22157789
TI  - Professional excellence and career advancement in nursing: a conceptual framework
      for clinical leadership development.
AB  - Increasingly, stakeholders in the health care community are recognizing nursing
      as key to solving the nation's health care issues. This acknowledgment provides a
      unique opportunity for nursing to demonstrate leadership by developing clinical
      nurse leaders to collaborate with the multidisciplinary care team in driving
      evidence-based, safe quality, cost-effective health care services. One approach
      for nursing success is standardizing the entry-level education for nurses and
      developing a uniform professional development and career advancement trajectory
      with appropriate incentives to encourage participation. A framework to guide and
      provide scientific evidence of how frontline nurses can be engaged will be
      paramount. The model for professional excellence and career advancement provides
      a framework that offers a clear path for researchers to examine variables
      influencing nurses' professional development and career advancement in a
      systematic manner. Professional Excellence and Career Advancement in Nursing
      underscores professional preparedness of a registered nurse as central to
      leadership development. It also describes the elements that influence nurses'
      participation in professional development and career advancement under 4 main
      categories emphasizing mentorship and self-efficacy as essential variables.

PMID- 22157790
TI  - Chief nursing officer to chief executive officer: lessons learned.
AB  - As health care in the United States continues to evolve, more chief nursing
      officers are moving to the role of chief executive officer. This article
      describes lessons learned from a chief nursing officer who is currently serving
      as a chief executive officer of an academic medical center. Eight lessons are
      described followed by reflective questions encouraging the reader to reflect and
      begin to internalize the experiences of the past role of a chief nursing officer
      and their applicability to the potential future role of a chief executive
      officer. The eight lessons explored are as follows: (1) you know more than you
      think you know; (2) nursing is part of the picture, not the whole picture; (3)
      relationships matter; (4) trust your gut; (5) if you do not have the right team,
      change it; (6) simple is better; (7) use your accountability to the board to
      accomplish your goals; and (8) to serve the organization well, you must keep
      yourself at your personal best.

PMID- 22157791
TI  - NAQ forum: a discussion with nurse CEOs.

PMID- 22157792
TI  - Betrayed trust: healing a broken hospital through servant leadership.
AB  - An investigative reporter with The Washington Post broke the news of a no
      confidence vote by the medical staff of a hospital in the suburbs of Washington,
      District of Columbia. The chaos that followed created a perfect storm for needed
      change and offered the rare opportunity for unbridled deep and creative
      collaboration. Issues the hospital faced as a result of this crisis and
      subsequent events that tested the authenticity of change are summarized. This
      article focuses on the approach used by the registered nurse chief executive
      officer (RN-CEO) to humanize the hospital, viewing it as though it were a patient
      and leading a clinical approach to organizational recovery and health. The
      relationship that developed between the medical staff leaders and the RN-CEO was
      pivotal to the hospital's recovery and evolved as a hybrid of servant leadership.
      Outcomes achieved over a 7-year period and attributable to this relational model
      are summarized. Finally, the RN-CEO shares lessons learned through experience and
      reflection and advice for nurses interested in pursuing executive leadership
      roles.

PMID- 22157793
TI  - Executive nursing leader in action: Dr Bernadette Melnyck.

PMID- 22157794
TI  - Emerging nursing regulation in developing countries.

PMID- 22157796
TI  - News from the front.

PMID- 22157795
TI  - Technology enables value-based nursing care.
AB  - Although America spends more per capita on health care than any other nation in
      the world, care is neither consistent nor effective. The rising prominence of
      value-based care initiatives gives nurse executives an opportunity to lead
      clinical practice into a new evidence-fueled decision-making era. Technology
      holds the key to making emerging better practices and the latest clinical
      breakthroughs available at the point of care.

PMID- 22157797
TI  - Skin disorders in the neonatal intensive care unit of a central hospital.
AB  - Cutaneous abnormalities in the newborn are usually benign and transitory.
      However, they may sometimes be extremely distressing both for parents and the
      medical staff, presenting with significant morbidity and mortality. The aim of
      this study was to access the clinical features of different skin disorders in a
      series of newborns, at a level III neonatal intensive care unit (NICU) in the
      Northern Region of Portugal, and review some of the most impressive cases.
      Between January 1997 and December 2010, 27 patients were found to have an
      important cutaneous condition that required admission to the NICU. The most
      frequent presentations were vesicles and pustules (n=8; 29.6%), followed by
      erythroderma (n=7; 25.9%), atrophic (n=5; 18.5%) and vascular lesions (n=4;
      14.8%). Four (14.8%) patients died in the neonatal period, and further 4
      afterwards. Genetic studies, when available, revealed three chromosomal disorders
      and 6 gene mutations. Overall, skin disorders were not a leading cause of NICU
      admission (0.43%), but were associated with significant morbidity and mortality.

PMID- 22157798
TI  - Childhood maltreatment and the structure of common psychiatric disorders.
AB  - BACKGROUND: Previous research suggests that various types of childhood
      maltreatment frequently co-occur and confer risk for multiple psychiatric
      diagnoses. This non-specific pattern of risk may mean that childhood maltreatment
      increases vulnerability to numerous specific psychiatric disorders through
      diverse, specific mechanisms or that childhood maltreatment engenders a
      generalised liability to dimensions of psychopathology. Although these competing
      explanations have different implications for intervention, they have never been
      evaluated empirically. AIMS: We used a latent variable approach to estimate the
      associations of childhood maltreatment with underlying dimensions of
      internalising and externalising psychopathology and with specific disorders after
      accounting for the latent dimensions. We also examined gender differences in
      these associations. METHOD: Data were drawn from a nationally representative
      survey of 34 653 US adults. Lifetime DSM-IV psychiatric disorders were assessed
      using the AUDADIS-IV. Physical, sexual and emotional abuse and neglect were
      assessed using validated measures. Analyses controlled for other childhood
      adversities and sociodemographics. RESULTS: The effects were fully mediated
      through the latent liability dimensions, with an impact on underlying liability
      levels to internalising and externalising psychopathology rather than specific
      psychiatric disorders. Important gender differences emerged with physical abuse
      associated only with externalising liability in men, and only with internalising
      liability in women. Neglect was not significantly associated with latent
      liability levels. CONCLUSIONS: The association between childhood maltreatment and
      common psychiatric disorders operates through latent liabilities to experience
      internalising and externalising psychopathology, indicating that the prevention
      of maltreatment may have a wide range of benefits in reducing the prevalence of
      many common mental disorders. Different forms of abuse have gender-specific
      consequences for the expression of internalising and externalising
      psychopathology, suggesting gender-specific aetiological pathways between
      maltreatment and psychopathology.

PMID- 22157799
TI  - Mortality in people with depressive, anxiety and alcohol use disorders in
      Finland.
AB  - BACKGROUND: Mental disorders are associated with increased mortality, but
      population-based surveys with reliable diagnostic procedures controlling for
      somatic health status are scarce. AIMS: To assess excess mortality associated
      with depressive, anxiety and alcohol use disorders and the principal causes of
      death. METHOD: In a nationally representative sample of Finns aged 30-70 years,
      psychiatric disorders were diagnosed with the Composite International Diagnostic
      Interview. After an 8-year follow-up period, vital status and cause of death of
      each participant was obtained from national registers. RESULTS: After adjusting
      for sociodemographic factors, health status and smoking, depressive (hazard ratio
      (HR) = 1.97) and alcohol use disorders (HR = 1.72) were statistically
      significantly associated with mortality. Risk of unnatural death was increased
      among individuals diagnosed with anxiety disorders or alcohol dependence.
      CONCLUSIONS: Individuals with depressive and alcohol use disorders have an
      increased mortality risk comparable with many chronic somatic conditions, that is
      only partly attributable to differences in sociodemographic, somatic health
      status and hazardous health behaviour.

PMID- 22157800
TI  - Filmed v. live social contact interventions to reduce stigma: randomised
      controlled trial.
AB  - BACKGROUND: Direct social contact interventions are known to reduce mental health
      stigma. Filmed social contact may be equally effective and have practical and
      cost advantages. AIMS: To compare the effectiveness of a DVD, a live intervention
      and a lecture control, in reducing stigma, testing the hypotheses that: (a) DVD
      and live interventions will be equally effective; and (b) the interventions with
      social contact (DVD/live) will be more effective than the lecture. Cost
      effectiveness, process and acceptability are also assessed. METHOD: Student
      nurses were randomised to: (a) watch a DVD of service users/informal carers
      talking about their experiences, (b) watch a similar live presentation, or (c)
      attend a lecture. Primary outcomes were changes in attitudes (using the Mental
      Illness: Clinicians Attitudes Scale, MICA), emotional reactions (using the
      Emotional Reactions to Mental Illness Scale, ERMIS), intended proximity (using
      the Reported and Intended Behaviour Scale, RIBS), and knowledge (using the Social
      Contact Intended Learning Outcomes, SCILO), immediately after the intervention
      and at 4-month follow-up. RESULTS: For the 216 participants, there were no
      differences between the DVD and live groups on MICA, ERMIS or RIBS scores. The
      DVD group had higher SCILO (knowledge) scores. The combined social contact group
      (DVD/live) had better MICA and RIBS scores than the lecture group, the latter
      difference maintained at 4 months. The DVD was the most cost-effective of the
      interventions, and the live session the most popular. CONCLUSIONS: Our hypotheses
      were confirmed. This study supports the wider use of filmed social contact
      interventions to reduce stigma about mental illness.

PMID- 22157801
TI  - Risk factors for repetition and suicide following self-harm in older adults:
      multicentre cohort study.
AB  - BACKGROUND: Older adults have elevated suicide rates. Self-harm is the most
      important risk factor for suicide. There are few population-based studies of self
      harm in older adults. AIMS: To calculate self-harm rates, risk factors for
      repetition and rates of suicide following self-harm in adults aged 60 years and
      over. METHOD: We studied a prospective, population-based self-harm cohort
      presenting to six general hospitals in three cities in England during 2000 to
      2007. RESULTS: In total 1177 older adults presented with self-harm and 12.8%
      repeated self-harm within 12 months. Independent risk factors for repetition were
      previous self-harm, previous psychiatric treatment and age 60-74 years. Following
      self-harm, 1.5% died by suicide within 12 months. The risk of suicide was 67
      times that of older adults in the general population. Men aged 75 years and above
      had the highest suicide rates. CONCLUSIONS: Older adults presenting to hospital
      with self-harm are a high-risk group for subsequent suicide, particularly older
      men.

PMID- 22157802
TI  - Exploring the association between social capital and depressive symptoms: results
      of a survey in German information and communication technology companies.
AB  - OBJECTIVE: This study examines the association between social capital at work and
      depressive symptoms in employees. METHODS: Data for this cross-sectional study
      were collected through an online survey with the full population of employees
      from six companies in the German information and communication technology sector
      (response rate: 58.4%). A multivariate logistic regression analysis was
      performed. RESULTS: Results of data from a total of 328 employees suggest that,
      after controlling for sociodemographic factors, health awareness, and job strain,
      lower levels of perceived social capital at work are associated with the
      experience of depressive symptoms (OR = 0.76; 95% CI: 0.64-0.90). CONCLUSIONS:
      Our findings suggest that characteristics of high social capital at work, such as
      an established environment of trust and a sense of common values and convictions,
      could be an essential resource for preventing depressive disorders.

PMID- 22157803
TI  - Identifying experiential expertise to support people with diabetes mellitus in
      applying for and participating effectively in paid work: a qualitative study.
AB  - OBJECTIVE: Identifying and describing successful diabetes-related (SDR) behaviors
      from reports by experiential experts to support people with diabetes in applying
      for and participating effectively in paid work. METHODS: Data were collected by
      conducting in-depth interviews with experiential experts with diabetes (N = 47).
      RESULTS: A comprehensive set of SDR behaviors that can help people with diabetes
      apply for and participate in paid work. The most important factors were reported
      to be the ability to anticipate problems in job applications, effective self
      management activities to prevent and/or respond to hypoglycemia and hyperglycemia
      at work, informing relevant others in the workplace, and successfully negotiating
      with employers about adjustments to work conditions. CONCLUSIONS: A set of work
      related SDR behaviors was identified. After validation by experiential experts
      and professionals, these could be translated into recommendations and tested in
      experiments in self-management programs.

PMID- 22157804
TI  - Evaluation of the correlation between genetic damage and occupational chromate
      exposure through BNMN frequencies.
AB  - OBJECTIVE: To evaluate the correlation between chromate exposure and binucleated
      cells with micronuclei (BNMN) frequencies in chromate production workers and
      explore the ideal biomarker to detect early DNA damage. METHODS: There are 79
      workers and 112 peasants in this study. Chromium concentrations in the air (CrA),
      blood (CrB), and urine (CrU) were detected. BNMN frequencies were also counted.
      RESULTS: The CrA, CrB, CrU, and BNMN frequencies of the exposure group were
      higher than those of the control group; BNMN frequencies were positively
      correlated with CrB and CrU; natural logarithm (Ln) BNMN was regressed on CrB,
      CrU, and CrA by linear models. CONCLUSIONS: The increases in CrB, CrU, and BNMN
      frequencies caused by lower CrA level suggest BNMN frequencies could be used to
      detect early DNA damage in the chromate production health surveillance.

PMID- 22157805
TI  - Disability pension among Swedish twins--prevalence over 16 years and associations
      with sociodemographic factors in 1992.
AB  - OBJECTIVE: To investigate annual prevalence of disability pension (DP) from 1992
      to 2007 and associations with sociodemographic factors in 1992. METHODS: All
      twins born between 1928 and 1958 were identified from the Swedish Twin Registry
      and linked to national records on DP. Descriptive statistics and logistic
      regressions were applied. RESULTS: The annual prevalence of DP was 10.7% (9.6% to
      11.3%). High age (odds ratio [OR] 9.17; 95% confidence interval [CI] 8.43 to
      9.98), low education (OR 4.84; 95% CI 4.31 to 5.42), and being unmarried (OR
      2.36; 95% CI 2.22 to 2.50) were associated with DP. The associations remained
      after adjusting for familial factors. CONCLUSIONS: The fact that the associations
      remained after control for familial factors indicates that factors not shared by
      family members, such as choices in adulthood, are of relevance for the
      associations found.

PMID- 22157806
TI  - Burnout and behavior-related health risk factors: results from the population
      based Finnish Health 2000 study.
AB  - OBJECTIVE: To explore the relationship between burnout and behavior-related
      health risk factors. METHODS: We collected data from a population-based sample (n
      = 3264) through interviews, questionnaires, and health examinations. Burnout was
      assessed using the Maslach Burnout Inventory-General Survey. Smoking, alcohol
      consumption, and leisure-time physical activity were self-reported. Obesity was
      based on measurements at screening. RESULTS: Burnout and exhaustion were
      associated with a higher likelihood of risk factors. More specifically, burnout
      syndrome was related to low physical activity and obesity, exhaustion dimension
      to low physical activity and heavy drinking, cynicism dimension to low physical
      activity, and diminished professional efficacy to low physical activity, obesity,
      and lower likelihood of heavy drinking. CONCLUSIONS: Improving working conditions
      and psychoeducation on recommended ways of coping and recovery could help to
      prevent negative health consequences of chronic work stress.

PMID- 22157807
TI  - Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic
      myeloid leukemia in blastic phase.
AB  - Nilotinib is a selective inhibitor of BCR-ABL approved for use in newly diagnosed
      and imatinib-resistant or -intolerant patients with chronic myeloid leukemia
      (CML) in chronic phase. In this study, 400 mg of nilotinib was administered twice
      daily to the patients with myeloid (MBP, n=105) or lymphoid blastic phase (LBP,
      n=31) CML. After a minimum follow-up of 24 months, major hematologic responses
      were observed in 60% (MBP) and 59% (LBP) of patients. Major cytogenetic responses
      (MCyR) were attained in 38% (MBP) and 52% (LBP) of patients; and complete
      cytogenetic responses in 30% and 32%, respectively. Median duration of MCyR was
      10.8 (MBP) and 3.2 months (LBP). Median overall survival was 10.1 (MBP) and 7.9
      (LBP) months with 12- and 24-month survival of 42% (MBP 44%, LBP 35%) and 27%
      (MBP 32%, LBP 10%), respectively. Twelve MBP patients and two LBP patients
      received subsequent stem cell transplantation. Myelosuppression was frequent,
      with grade 3/4 neutropenia, thrombocytopenia, and anemia in 68%, 63% and 47% of
      patients, respectively. Grade 3/4 hypophosphatemia, hyperbilirubinemia and lipase
      elevation were observed in 15%, 11% and 11% of patients, respectively. Nilotinib
      has significant efficacy in patients with BP CML, but given the limited long-term
      survival of these patients, novel agents are needed.

PMID- 22157808
TI  - Dysregulation of TNFalpha-induced necroptotic signaling in chronic lymphocytic
      leukemia: suppression of CYLD gene by LEF1.
AB  - Impaired cell death program has been noted as one of the hallmarks of chronic
      lymphocytic leukemia (CLL) and contributes to its accumulation of malignant
      monoclonal B cells as well as to chemotherapy resistance. A cell can die through
      the apoptosis or necrosis pathway. Recent investigations suggest that in
      apoptotic-deficient conditions, such as most types of cancer, a process of
      programmed necrosis, called necroptosis, prevails. However, the detailed
      molecular mechanisms underlying this alternative cell death pathway are still not
      fully understood. Here we demonstrate that CLL cells failed to undergo
      necroptosis upon stimulation of TNFalpha combined with pan-caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD). Two core components of
      necroptotic machine, RIP3 and deubiquitinase cylindromatosis (CYLD), are markedly
      downregulated in CLL. Moreover, we identified lymphoid enhancer-binding factor 1
      (LEF1), a downstream effector of the Wnt/beta-catenin pathway, as a transcription
      repressor of CYLD in CLL. Knocking down LEF1 sensitizes CLL cells to
      TNFalpha/zVAD-induced necroptosis. The present investigation provides the first
      evidence that CLL cells have defects not only in apoptotic program but also in
      necroptotic signaling. Targeting the key regulators of necroptotic machine, such
      as LEF1, to restore this pathway may represent a novel approach for CLL
      treatment.

PMID- 22157809
TI  - Long-term WT1 peptide vaccination for patients with acute myeloid leukemia with
      minimal residual disease.

PMID- 22157811
TI  - Effect of motor control training on muscle size and football games missed from
      injury.
AB  - PURPOSE: This panel-randomized intervention trial was designed to examine the
      effect of a motor control training program for elite Australian Football League
      players with and without low back pain (LBP). METHODS: The outcome measures
      included cross-sectional area (CSA) and symmetry of multifidus, quadratus
      lumborum, and psoas muscles and the change in CSA of the trunk in response to an
      abdominal drawing-in task. These measures of muscle size and function were
      performed using magnetic resonance imaging. Availability of players for
      competition games was used to assess the effect of the intervention on the
      occurrence of injuries. The motor control program involved performance of
      voluntary contractions of the multifidus and transversus abdominis muscles while
      receiving feedback from ultrasound imaging. Because all players were to receive
      the intervention, the trial was delivered as a stepped-wedge design with three
      treatment arms (a 15-wk intervention, a 8-wk intervention, and a waitlist control
      who received a 7-wk intervention toward the end of the playing season). Players
      participated in a Pilates program when they were not receiving the intervention.
      RESULTS: The intervention program was associated with an increase in multifidus
      muscle size relative to results in the control group. The program was also
      associated with an improved ability to draw-in the abdominal wall. Intervention
      was commensurate with an increase in availability for games and a high level of
      perceived benefit. CONCLUSIONS: The motor control program delivered to elite
      footballers was effective, with demonstrated changes in the size and control of
      the targeted muscles. In this study, footballers who received the intervention
      early in the season missed fewer games because of injury than those who received
      it late in the playing season.

PMID- 22157812
TI  - Synthetic, multi-layer, self-oscillating vocal fold model fabrication.
AB  - Sound for the human voice is produced via flow-induced vocal fold vibration. The
      vocal folds consist of several layers of tissue, each with differing material
      properties. Normal voice production relies on healthy tissue and vocal folds, and
      occurs as a result of complex coupling between aerodynamic, structural dynamic,
      and acoustic physical phenomena. Voice disorders affect up to 7.5 million
      annually in the United States alone and often result in significant financial,
      social, and other quality-of-life difficulties. Understanding the physics of
      voice production has the potential to significantly benefit voice care, including
      clinical prevention, diagnosis, and treatment of voice disorders. Existing
      methods for studying voice production include in vivo experimentation using human
      and animal subjects, in vitro experimentation using excised larynges and
      synthetic models, and computational modeling. Owing to hazardous and difficult
      instrument access, in vivo experiments are severely limited in scope. Excised
      larynx experiments have the benefit of anatomical and some physiological realism,
      but parametric studies involving geometric and material property variables are
      limited. Further, they are typically only able to be vibrated for relatively
      short periods of time (typically on the order of minutes). Overcoming some of the
      limitations of excised larynx experiments, synthetic vocal fold models are
      emerging as a complementary tool for studying voice production. Synthetic models
      can be fabricated with systematic changes to geometry and material properties,
      allowing for the study of healthy and unhealthy human phonatory aerodynamics,
      structural dynamics, and acoustics. For example, they have been used to study
      left-right vocal fold asymmetry, clinical instrument development, laryngeal
      aerodynamics, vocal fold contact pressure, and subglottal acoustics (a more
      comprehensive list can be found in Kniesburges et al.) Existing synthetic vocal
      fold models, however, have either been homogenous (one-layer models) or have been
      fabricated using two materials of differing stiffness (two-layer models). This
      approach does not allow for representation of the actual multi-layer structure of
      the human vocal folds that plays a central role in governing vocal fold flow
      induced vibratory response. Consequently, one- and two-layer synthetic vocal fold
      models have exhibited disadvantages such as higher onset pressures than what are
      typical for human phonation (onset pressure is the minimum lung pressure required
      to initiate vibration), unnaturally large inferior-superior motion, and lack of a
      "mucosal wave" (a vertically-traveling wave that is characteristic of healthy
      human vocal fold vibration). In this paper, fabrication of a model with multiple
      layers of differing material properties is described. The model layers simulate
      the multi-layer structure of the human vocal folds, including epithelium,
      superficial lamina propria (SLP), intermediate and deep lamina propria (i.e.,
      ligament; a fiber is included for anterior-posterior stiffness), and muscle
      (i.e., body) layers. Results are included that show that the model exhibits
      improved vibratory characteristics over prior one- and two-layer synthetic
      models, including onset pressure closer to human onset pressure, reduced inferior
      superior motion, and evidence of a mucosal wave.

PMID- 22157810
TI  - Modulation of RhoGTPases improves the behavioral phenotype and reverses
      astrocytic deficits in a mouse model of Rett syndrome.
AB  - RhoGTPases are crucial molecules in neuronal plasticity and cognition, as
      confirmed by their role in non-syndromic mental retardation. Activation of brain
      RhoGTPases by the bacterial cytotoxic necrotizing factor 1 (CNF1) reshapes the
      actin cytoskeleton and enhances neurotransmission and synaptic plasticity in
      mouse brains. We evaluated the effects of a single CNF1 intracerebroventricular
      inoculation in a mouse model of Rett syndrome (RTT), a rare neurodevelopmental
      disorder and a genetic cause of mental retardation, for which no effective
      therapy is available. Fully symptomatic MeCP2-308 male mice were evaluated in a
      battery of tests specifically tailored to detect RTT-related impairments. At the
      end of behavioral testing, brain sections were immunohistochemically
      characterized. Magnetic resonance imaging and spectroscopy (MRS) were also
      applied to assess morphological and metabolic brain changes. The CNF1
      administration markedly improved the behavioral phenotype of MeCP2-308 mice. CNF1
      also dramatically reversed the evident signs of atrophy in astrocytes of mutant
      mice and restored wt-like levels of this cell population. A partial rescue of the
      overexpression of IL-6 cytokine was also observed in RTT brains. CNF1-induced
      brain metabolic changes detected by MRS analysis involved markers of glial
      integrity and bioenergetics, and point to improved mitochondria functionality in
      CNF1-treated mice. These results clearly indicate that modulation of brain
      RhoGTPases by CNF1 may constitute a totally innovative therapeutic approach for
      RTT and, possibly, for other disorders associated with mental retardation.

PMID- 22157813
TI  - Evaluation of paraoxonase 1 arylesterase activity and lipid peroxide levels in
      patients with type 1 diabetes.
AB  - INTRODUCTION: Poor metabolic control of type 1 diabetes is one of the most
      important factors accelerating the development of late diabetic complications.
      Several other factors that might contribute to this process are currently being
      investigated. Low paraoxonase 1 (PON1) activity and high lipid peroxide (LPO)
      levels contribute to endothelial damage, but it remains unclear whether they are
      critical for the development of late diabetic complications. OBJECTIVES: The aim
      of the study was to evaluate PON1 arylesterase activity and LPO levels in
      patients with type 1 diabetes and to investigate whether these parameters are
      associated with metabolic control and late complications. Moreover, we aimed to
      establish whether PON1 activity and LPO levels differ between women and men with
      type 1 diabetes. PATIENTS AND METHODS: The study involved 80 patients with type 1
      diabetes and 24 healthy subjects. PON1 activity was measured by a
      spectrophotometric method. LPO levels were measured by a commercial assay kit.
      RESULTS: Diabetic patients had lower PON1 activity and higher LPO levels than
      healthy people. We observed a negative correlation between PON1 activity and LPO
      levels in diabetic patients. There was no association between PON1 activity or
      LPO levels and metabolic parameters or late diabetic complications. There was a
      positive correlation between LPO levels and the body mass index (BMI) in women
      with type 1 diabetes. CONCLUSIONS: Our study showed that low PON1 activity and
      high LPO levels are not the most critical factors involved in late diabetic
      complications in type 1 diabetes. Increased LPO levels in women with type 1
      diabetes may result from enhanced lipogenesis in this subgroup compared with
      diabetic men.

PMID- 22157814
TI  - The tudor domain protein kumo is required to assemble the nuage and to generate
      germline piRNAs in Drosophila.
AB  - In Drosophila ovaries, distinct Piwi-interacting RNA (piRNA) pathways defend
      against transposons in somatic and germline cells. Germline piRNAs predominantly
      arise from bidirectional clusters and are amplified by the ping-pong cycle. In
      this study, we characterize a novel Drosophila gene, kumo and show that it
      encodes a conserved germline piRNA pathway component. Kumo contains five tudor
      domains and localizes to nuage, a unique structure present in animal germline
      cells, which is considered to be the processing site for germline piRNAs.
      Transposons targeted by the germline piRNA pathway are derepressed in kumo mutant
      females. Moreover, germline piRNA production is significantly reduced in mutant
      ovaries, thereby indicating that kumo is required to generate germline piRNAs.
      Kumo localizes to the nuage as well as to nucleus early female germ cells, where
      it is required to maintain cluster transcript levels. Our data suggest that kumo
      facilitates germline piRNA production by promoting piRNA cluster transcription in
      the nucleus and piRNA processing at the nuage.

PMID- 22157815
TI  - The SNF2-like helicase HELLS mediates E2F3-dependent transcription and cellular
      transformation.
AB  - The activating E2F-transcription factors are best known for their dependence on
      the Retinoblastoma protein and their role in cellular proliferation. E2F3 is
      uniquely amplified in specific human tumours where its expression is inversely
      correlated with the survival of patients. Here, E2F3B interaction partners were
      identified by mass spectrometric analysis. We show that the SNF2-like helicase
      HELLS interacts with E2F3A in vivo and cooperates with its oncogenic functions.
      Depletion of HELLS severely perturbs the induction of E2F-target genes, hinders
      cell-cycle re-entry and growth. Using chromatin immmunoprecipitation coupled to
      sequencing, we identified genome-wide targets of HELLS and E2F3A/B. HELLS binds
      promoters of active genes, including the trithorax-related MLL1, and co-regulates
      E2F3-dependent genes. Strikingly, just as E2F3, HELLS is overexpressed in human
      tumours including prostate cancer, indicating that either factor may contribute
      to the malignant progression of tumours. Our work reveals that HELLS is important
      for E2F3 in tumour cell proliferation.

PMID- 22157816
TI  - Rescue of tropomyosin deficiency in Drosophila and human cancer cells by
      synaptopodin reveals a role of tropomyosin alpha in RhoA stabilization.
AB  - Tropomyosins are widespread actin-binding proteins that influence numerous
      cellular functions including actin dynamics, cell migration, tumour suppression,
      and Drosophila oocyte development. Synaptopodin is another actin-binding protein
      with a more restricted expression pattern in highly dynamic cell compartments
      such as kidney podocyte foot processes, where it promotes RhoA signalling by
      blocking the Smurf1-mediated ubiquitination of RhoA. Here, we show that
      synaptopodin has a shorter half-life but shares functional properties with the
      highly stable tropomyosin. Transgenic expression of synaptopodin restores oskar
      mRNA localization in Drosophila oocytes mutant for TmII, thereby rescuing
      germline differentiation and fertility. Synaptopodin restores stress fibres in
      tropomyosin-deficient human MDA-MB 231 breast cancer cells and TPMalpha-depleted
      fibroblasts. Gene silencing of TPMalpha but not TPMbeta causes loss of stress
      fibres by promoting Smurf1-mediated ubiquitination and proteasomal degradation of
      RhoA. Functionally, overexpression of synaptopodin or RhoA(K6,7R) significantly
      reduces MDA-MB 231 cell migration. Our findings elucidate RhoA stabilization by
      structurally unrelated actin-binding proteins as a conserved mechanism for
      regulation of stress fibre dynamics and cell motility in a cell type-specific
      fashion.

PMID- 22157817
TI  - Mechanoinduction of lymph vessel expansion.
AB  - In the mammalian embryo, few mechanical signals have been identified to influence
      organ development and function. Here, we report that an increase in the volume of
      interstitial or extracellular fluid mechanically induces growth of an organ
      system, that is, the lymphatic vasculature. We first demonstrate that lymph
      vessel expansion in the developing mouse embryo correlates with a peak in
      interstitial fluid pressure and lymphatic endothelial cell (LEC) elongation. In
      'loss-of-fluid' experiments, we then show that aspiration of interstitial fluid
      reduces the length of LECs, decreases tyrosine phosphorylation of vascular
      endothelial growth factor receptor-3 (VEGFR3), and inhibits LEC proliferation.
      Conversely, in 'gain-of-fluid' experiments, increasing the amount of interstitial
      fluid elongates the LECs, and increases both VEGFR3 phosphorylation and LEC
      proliferation. Finally, we provide genetic evidence that beta1 integrins are
      required for the proliferative response of LECs to both fluid accumulation and
      cell stretching and, therefore, are necessary for lymphatic vessel expansion and
      fluid drainage. Thus, we propose a new and physiologically relevant mode of
      VEGFR3 activation, which is based on mechanotransduction and is essential for
      normal development and fluid homeostasis in a mammalian embryo.

PMID- 22157818
TI  - Phagosomal proteolysis in dendritic cells is modulated by NADPH oxidase in a pH
      independent manner.
AB  - The level of proteolysis within phagosomes of dendritic cells (DCs) is thought to
      be tightly regulated, as it directly impacts the cell's efficiency to process
      antigen. Activity of the antimicrobial effector NADPH oxidase (NOX2) has been
      shown to reduce levels of proteolysis within phagosomes of both macrophages and
      DCs. However, the proposed mechanisms underlying these observations in these two
      myeloid cell lineages are dissimilar. Using real-time analysis of lumenal
      microenvironmental parameters within phagosomes in live bone marrow-derived DCs,
      we show that the levels of phagosomal proteolysis are diminished in the presence
      of NOX2 activity, but in contrast to previous reports, the acidification of the
      phagosome is largely unaffected. As found in macrophages, we show that NOX2
      controls phagosomal proteolysis in DCs through redox modulation of local cysteine
      cathepsins. Aspartic cathepsins were unaffected by redox conditions, indicating
      that NOX2 skews the relative protease activities in these antigen processing
      compartments. The ability of DC phagosomes to reduce disulphides was also
      compromised by NOX2 activity, implicating this oxidase in the control of an
      additional antigen processing chemistry of DCs.

PMID- 22157819
TI  - Dysregulation of DNA polymerase kappa recruitment to replication forks results in
      genomic instability.
AB  - Translesion synthesis polymerases (TLS Pols) are required to tolerate DNA lesions
      that would otherwise cause replication arrest and cell death. Aberrant expression
      of these specialized Pols may be responsible for increased mutagenesis and loss
      of genome integrity in human cancers. The molecular events that control the usage
      of TLS Pols in non-pathological conditions remain largely unknown. Here, we show
      that aberrant recruitment of TLS Polkappa to replication forks results in genomic
      instability and can be mediated through the loss of the deubiquitinase USP1.
      Moreover, artificial tethering of Polkappa to proliferating cell nuclear antigen
      (PCNA) circumvents the need for its ubiquitin-binding domain in the promotion of
      genomic instability. Finally, we show that the loss of USP1 leads to a dramatic
      reduction of replication fork speed in a Polkappa-dependent manner. We propose a
      mechanism whereby reversible ubiquitination of PCNA can prevent spurious TLS Pol
      recruitment and regulate replication fork speed to ensure the maintenance of
      genome integrity.

PMID- 22157820
TI  - Dynamic long-range chromatin interactions control Myb proto-oncogene
      transcription during erythroid development.
AB  - The key haematopoietic regulator Myb is essential for coordinating proliferation
      and differentiation. ChIP-Sequencing and Chromosome Conformation Capture (3C)
      Sequencing were used to characterize the structural and protein-binding dynamics
      of the Myb locus during erythroid differentiation. In proliferating cells
      expressing Myb, enhancers within the Myb-Hbs1l intergenic region were shown to
      form an active chromatin hub (ACH) containing the Myb promoter and first intron.
      This first intron was found to harbour the transition site from transcription
      initiation to elongation, which takes place around a conserved CTCF site. Upon
      erythroid differentiation, Myb expression is downregulated and the ACH
      destabilized. We propose a model for Myb activation by distal enhancers
      dynamically bound by KLF1 and the GATA1/TAL1/LDB1 complex, which primarily
      function as a transcription elongation element through chromatin looping.

PMID- 22157821
TI  - VprBP binds full-length RAG1 and is required for B-cell development and V(D)J
      recombination fidelity.
AB  - The N-terminus of full-length RAG1, though dispensable for RAG1/2 cleavage
      activity, is required for efficient V(D)J recombination. This region supports
      RING E3 ubiquitin ligase activity in vitro, but whether full-length RAG1
      functions as a single subunit or a multi-subunit E3 ligase in vivo is unclear. We
      show the multi-subunit cullin RING E3 ligase complex VprBP/DDB1/Cul4A/Roc1
      associates with full-length RAG1 through VprBP. This complex is assembled into
      RAG protein-DNA complexes, and supports in-vitro ubiquitylation activity that is
      insensitive to RAG1 RING domain mutations. Conditional B lineage-specific VprBP
      disruption arrests B-cell development at the pro-B-to-pre-B cell transition, but
      this block is bypassed by expressing rearranged immunoglobulin transgenes. Mice
      with a conditional VprBP disruption show modest reduction of D-J(H)
      rearrangement, whereas V(H)-DJ(H) and V(kappa)-J(kappa) rearrangements are
      severely impaired. D-J(H) coding joints from VprBP-insufficent mice show longer
      junctional nucleotide insertions and a higher mutation frequency in D and J
      segments than normal. These data suggest full-length RAG1 recruits a cullin RING
      E3 ligase complex to ubiquitylate an unknown protein(s) to limit error-prone
      repair during V(D)J recombination.

PMID- 22157823
TI  - Correspondence.

PMID- 22157824
TI  - On alert for violence in the ICU.

PMID- 22157822
TI  - Three-dimensional structure of basal body triplet revealed by electron cryo
      tomography.
AB  - Basal bodies and centrioles play central roles in microtubule (MT)-organizing
      centres within many eukaryotes. They share a barrel-shaped cylindrical structure
      composed of nine MT triplet blades. Here, we report the structure of the basal
      body triplet at 33 A resolution obtained by electron cryo-tomography and 3D
      subtomogram averaging. By fitting the atomic structure of tubulin into the EM
      density, we built a pseudo-atomic model of the tubulin protofilaments at the core
      of the triplet. The 3D density map reveals additional densities that represent
      non-tubulin proteins attached to the triplet, including a large inner circular
      structure in the basal body lumen, which functions as a scaffold to stabilize the
      entire basal body barrel. We found clear longitudinal structural variations along
      the basal body, suggesting a sequential and coordinated assembly mechanism. We
      propose a model in which delta-tubulin and other components participate in the
      assembly of the basal body.

PMID- 22157826
TI  - When is a story more than a story?

PMID- 22157828
TI  - Your role in protecting research participants.

PMID- 22157833
TI  - Up in the air.

PMID- 22157835
TI  - Nursing2012. Horizontal violence survey report.

PMID- 22157836
TI  - Suddenly losing our expert.

PMID- 22157837
TI  - Patient education series. Advance directives.

PMID- 22157838
TI  - Think "SAFE": four crucial elements for diabetes education.

PMID- 22157839
TI  - Our white rose program blooms and grows.

PMID- 22157840
TI  - Keeping older adults safe at home.

PMID- 22157841
TI  - Maggots, honey, and...sildenafil?

PMID- 22157842
TI  - Parvovirus B19 exposure during pregnancy.

PMID- 22157843
TI  - Acute talc inhalation.

PMID- 22157844
TI  - Effect of remote ischaemic preconditioning on ischaemic-reperfusion injury in
      pulmonary hypertensive infants receiving ventricular septal defect repair.
AB  - BACKGROUND: Remote ischaemic preconditioning (RIPC) can reduce ischaemic
      reperfusion injury in distant organs. The myocardial and pulmonary protective
      effect of RIPC in infants with pulmonary hypertension remains unclear. We
      conducted a randomized controlled trial to evaluate the effect of RIPC in infants
      receiving ventricular septal defect (VSD) repair. METHODS: We studied 55 infants
      with pulmonary hypertension undergoing VSD repair (RIPC group, n=27; control
      group, n=28). RIPC consisted of four 5 min cycles of lower limb ischaemia and
      reperfusion. Serum troponin I (TnI) concentrations were measured after induction
      of anaesthesia and at 1, 6, 12, and 24 h after surgery. Other clinical data such
      as inotropic score, lung compliance, alveolar-arterial oxygen gradient, oxygen
      index, mechanical ventilation time, and length of intensive care unit stay were
      also recorded at each interval. RESULTS: No differences in patient or surgical
      characteristics were observed between the two groups. There were no significant
      differences in postoperative TnI levels according to time (P=0.35) or the total
      amount of TnI release, expressed as the area under the curve over the 24 h after
      surgery [RIPC vs control: 207.6 (134.0) vs 274.6 (263.7) h ng ml(-1), P=0.24].
      All other clinical data were also comparable. CONCLUSIONS: RIPC does not reduce
      the postoperative TnI release after VSD repair in infants with pulmonary
      hypertension. Additionally, it is difficult to find significant clinical benefits
      of RIPC in this population. The effect of RIPC varies according to clinical
      situation and patient condition. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01313832.

PMID- 22157845
TI  - Electrocardiographic and haemodynamic alterations caused by three different test
      solutions of local anaesthetics to detect accidental intravascular injection in
      children.
AB  - BACKGROUND: The aim of this study was to investigate ECG and haemodynamic
      alterations provoked by a test dose of bupivacaine, epinephrine, and their
      combination. METHODS: Paediatric patients undergoing general anaesthesia were
      randomized into three groups. After anaesthesia induction and tracheal
      intubation, 0.2 ml kg(-1) (max. 3 ml) of the corresponding test solution was i.v.
      injected: bupivacaine 0.125% (Group B), bupivacaine 0.125% plus epinephrine 1:200
      000 (Group BE), or epinephrine 1:200 000 (Group E). ECG was printed and analysed
      post hoc. Non-invasive arterial pressure (AP) was measured at 1 and 2 min after
      test dose injection. Increases in T-wave of >= 25%, in heart rate (HR) of >= 10
      beats min(-1), and in systolic AP of >= 15 mm Hg above baseline value were
      considered a positive result. RESULTS: A total of 105 children aged 0.2-16
      (median 6.8) yr were enrolled. Test dose injection provoked T-wave elevation in
      0%, 85%, and 89% of patients in Groups B, BE, and E, respectively. A positive
      increase in HR was found in 0%, 68%, and 76%. A positive increase in AP at 1 min
      was found in 0%, 88%, and 94% and at 2 min in 0%, 42%, and 59%. A decrease in HR
      of >= 10 beats min(-1) was observed in 6%, 76%, and 69%. Alterations in T-wave
      and HR were significantly influenced by age. CONCLUSIONS: ECG and haemodynamic
      alterations after i.v. injection of a local anaesthetic test dose were
      significantly influenced by epinephrine. T-wave elevation, increase in AP, and
      changes in HR are highly reliable variables, particularly when age is taken into
      account.

PMID- 22157846
TI  - Cognitive errors detected in anaesthesiology: a literature review and pilot
      study.
AB  - BACKGROUND: Cognitive errors are thought-process errors, or thinking mistakes,
      which lead to incorrect diagnoses, treatments, or both. This psychology of
      decision-making has received little formal attention in anaesthesiology
      literature, although it is widely appreciated in other safety cultures, such as
      aviation, and other medical specialities. We sought to identify which types of
      cognitive errors are most important in anaesthesiology. METHODS: This study
      consisted of two parts. First, we created a cognitive error catalogue specific to
      anaesthesiology practice using a literature review, modified Delphi method with
      experts, and a survey of academic faculty. In the second part, we observed for
      those cognitive errors during resident physician management of simulated
      anaesthesiology emergencies. RESULTS: Of >30 described cognitive errors, the
      modified Delphi method yielded 14 key items experts felt were most important and
      prevalent in anaesthesiology practice (Table 1). Faculty survey responses
      narrowed this to a 'top 10' catalogue consisting of anchoring, availability bias,
      premature closure, feedback bias, framing effect, confirmation bias, omission
      bias, commission bias, overconfidence, and sunk costs (Table 2). Nine types of
      cognitive errors were selected for observation during simulated emergency
      management. Seven of those nine types of cognitive errors occurred in >50% of
      observed emergencies (Table 3). CONCLUSIONS: Cognitive errors are thought to
      contribute significantly to medical mishaps. We identified cognitive errors
      specific to anaesthesiology practice. Understanding the key types of cognitive
      errors specific to anaesthesiology is the first step towards training in
      metacognition and de-biasing strategies, which may improve patient safety.

PMID- 22157847
TI  - Discriminant analysis for anaesthetic decision-making: an intelligent recognition
      system for epidural needle insertion.
AB  - BACKGROUND: Incorrect placement of epidural catheters causes medical
      complications. We used linear discriminant analysis (LDA) to develop an
      intelligent recognition system (i-RS) in order to guide epidural placement and
      reduce physician error. METHODS: We analysed real-time dual-wavelength fibreoptic
      data recorded from the end of an epidural needle in a live porcine model. Two
      categories of tissue layers were necessary for correct placement of catheter:
      epidural space and ligamentum flavum. The data were tested using linear,
      quadratic and logistic parametric analysis to identify which method could
      distinguish the two anatomical structures. RESULTS: LDA was the best fit for our
      model. There was ~80% sensitivity and specificity for correct anatomical
      identification. Error rates based on cross-validation were 17.0% for the epidural
      space and 18.6% for ligamentum flavum. Error rates were greater with the 532 nm
      compared with 650 nm wavelength. CONCLUSIONS: The sensitivity and specificity of
      LDA for identifying the correct anatomical structure was similar to a physician
      who is an expert in epidural placement. Overall performance of an i-RS could be
      improved by expanding the database for decision-making and adding a category of
      uncertainty. This would reduce complications caused by incorrect epidural
      placement.

PMID- 22157848
TI  - Effect of intra-abdominal hypertension on left ventricular relaxation: a
      preliminary animal study.
AB  - BACKGROUND: In the intensive care unit, intra-abdominal hypertension (IAH) is a
      frequently encountered, life-threatening condition. The aim of this animal study
      was to evaluate the effect of IAH on left ventricular (LV) relaxation (i.e. the
      active phase of diastole). METHODS: Seven male rabbits were anaesthetized before
      mechanical ventilation. A 20 mm Hg increase in intra-abdominal pressure (IAP) was
      then induced by intraperitoneal infusion of 1.5% glycine solution. Haemodynamic
      parameters were recorded and the relaxation time constant tau (considered to be
      the best index of left ventricle relaxation) was calculated. All haemodynamic
      measurements were recorded at baseline and then after induction of IAH. RESULTS:
      A 20 mm Hg increase in IAP was not followed by a significant change in arterial
      pressure, but was associated with increases in central venous pressure (from 2 [
      2 to 6] to 7 [-2 to 12] mm Hg, P= 0.03), LV end-diastolic pressure (from 7 [6-8]
      to 15 [11-19] mm Hg, P= 0.04) and the relaxation time constant tau (from 16 [14
      18] to 43 [34-52] ms, P= 0.048). CONCLUSIONS: In this animal study, a 20 mm Hg
      increase in IAP impaired LV relaxation. Further studies are necessary to identify
      the causes of this impairment.

PMID- 22157849
TI  - Effects of alterations of inspiratory oxygen fractions on heart rate variability.
AB  - BACKGROUND: Changes in heart rate variability (HRV) during anaesthesia depend on
      multiple influences such as hypnosis, analgesia, surgical stress, and interacting
      drugs. Several recent studies have aimed to establish HRV-based monitoring tools
      to measure perioperative stress or anaesthetic depth. Although hyperoxic
      ventilation (HV) is known to alter autonomic cardiovascular regulation, there
      have been no studies investigating its influence on time- and frequency-domain
      analysis during general anaesthesia. Therefore, we have examined the effects of
      HV on cardiovascular neuroregulation of anaesthetized patients and conscious
      volunteers by analysis of relevant HRV parameters. METHODS: Fourteen healthy
      volunteers and 14 anaesthetized, ventilated ASA I patients sequentially breathed
      room air ( 0.21), pure oxygen ( 1.0), and then room air. During each episode,
      standardized HRV parameters were calculated from 5 min ECG recordings. RESULTS:
      HV significantly reduced HR and increased the standard deviation of RR interval
      values, the root mean square of successive RR interval differences, and the high
      frequency (HF) power of the spectral components, whereas the low-frequency (LF)
      power and the LF/HF ratio of HRV were reduced in both groups. All changes were
      reversible after was reduced to normoxia. CONCLUSIONS: In both healthy volunteers
      and anaesthetized patients, HV resulted in comparable and reversible changes of
      established HRV parameters. These changes might be relevant enough to bias HRV
      based analgesia and anaesthesia monitoring and could result in a clinically
      relevant misinterpretation of HRV parameters as indicators of anaesthetic depth
      during HV.

PMID- 22157850
TI  - Possible effects of anaesthetic management on the 1 yr followed-up risk of herpes
      zoster after Caesarean deliveries.
AB  - BACKGROUND: As general anaesthesia may compromise the immune system, it has been
      hypothesized that latent varicella-zoster virus is more likely to be reactivated
      and cause herpes zoster in mothers after Caesarean deliveries under general
      anaesthesia. Our study was thus aimed at investigating the risk of herpes zoster
      among women during the first year after Caesarean deliveries under either general
      or regional anaesthesia. METHODS: Two nationwide population-based data sets were
      utilized, including the Taiwan birth certificate registry and the Taiwan National
      Health Insurance Research Dataset. From 2001 to 2003, a total of 162 495 women
      underwent Caesarean delivery. Among them, 21 454 women received general
      anaesthesia, whereas 141 041 patients received regional anaesthesia. Each
      individual was followed for 1 yr to identify the subsequent occurrence of herpes
      zoster. Cox's proportional hazards regressions were performed for analysis.
      RESULTS: During the 1 yr follow-up period, 0.46% of the women receiving general
      anaesthesia experienced an episode of herpes zoster, compared with 0.34% of women
      receiving regional anaesthesia. In Caesarean deliveries, the use of general
      anaesthesia compared with regional anaesthesia was independently associated with
      a 1.29-fold (95% confidence interval=1.04-1.61) increase in the 1 yr risk of
      herpes zoster, after adjusting for maternal and infant characteristics.
      CONCLUSIONS: In this series, there was a small increased risk of herpes zoster in
      the year after Caesarean delivery with general anaesthesia. Future studies are
      needed to further investigate these findings.

PMID- 22157851
TI  - Gut microcirculatory and mitochondrial effects of hyperdynamic endotoxaemic shock
      and norepinephrine treatment.
AB  - BACKGROUND: Microcirculatory and mitochondrial dysfunction are important factors
      in the development of septic shock. In this study, we investigated the effects of
      fluid resuscitated endotoxaemic shock and norepinephrine treatment on intestinal
      microcirculation and mitochondrial function in sheep. METHODS: Eight
      anaesthetized sheep received an i.v. infusion of endotoxin. After 24 h, mean
      arterial pressure (MAP) was restored to baseline levels with a norepinephrine
      infusion. Five sheep served as sham experiments. Central and regional
      haemodynamics were monitored, and ileal microcirculation was evaluated with laser
      Doppler and sidestream dark-field videomicroscopy techniques. Gut mucosal
      acidosis was assessed by air tonometry, and ileal wall biopsies were analysed for
      mitochondrial activity. RESULTS: After 24 h of endotoxaemia, the animals had
      developed hyperdynamic shock with systemic and mucosal acidosis. Although
      superior mesenteric artery (SMA) flow was higher than the baseline values, ileal
      microcirculatory perfusion and mitochondrial complex I activity decreased. After
      norepinephrine was started, SMA flow, ileal microcirculation, and mucosal
      acidosis remained unchanged. Although no statistically significant difference
      could be demonstrated, norepinephrine increased mitochondrial complex I activity
      in five of the six animals from which ileal biopsies were taken. CONCLUSIONS:
      Although fluid resuscitated endotoxaemic shock increased regional blood flow,
      microcirculatory and mitochondrial alterations were still present. Restoring MAP
      with norepinephrine did not affect ileal microcirculation or mucosal acidosis,
      indicating that perfusion pressure manipulation is of limited importance to the
      intestinal microcirculation in established endotoxaemic shock.

PMID- 22157852
TI  - Popliteal sentinel lymph node biopsy is important in malignant melanoma of the
      distal lower extremities: a case report of acral lentiginous melanoma with
      simultaneous inguinal and popliteal lymph node micrometastases.

PMID- 22157854
TI  - Neurotherapeutics.

PMID- 22157855
TI  - New era for novel CNS drug development.

PMID- 22157856
TI  - Translating discoveries into medicine: psychiatric drug development in 2011.

PMID- 22157857
TI  - NIA commentary: translational issues in Alzheimer's disease drug development.

PMID- 22157858
TI  - Neuroscience networking: linking discovery to drugs.
AB  - Discoveries in the pre-clinical neurosciences have set the stage for bringing new
      therapies to patients affected by neurological disorders. The National lnstitute
      of Neurological Disorders and Stroke (NINDS) is dedicated to promoting the
      development of new therapies through its funding programs that range from basic
      neuroscience to translational research and finally clinical research to test the
      most promising new therapies in patients. In an effort to accelerate the
      translation of new discoveries to clinical practice, NINDS is piloting novel
      organizational strategies. In translational research, NINDS is taking the lead on
      the establishment of a 'virtual pharma' structure, through which researchers will
      partner with the NIH to accelerate the progress of drug development from early
      hit discovery through phase 1 clinical trials. In clinical research, the new
      Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) aims to
      promote the efficient implementation of scientifically sound, biomarker-informed
      phase 2 clinical trials that can be initiated by academic or industry
      investigators.

PMID- 22157859
TI  - New medications for substance use disorders: challenges and opportunities.
AB  - An increased understanding of the biological mechanisms underlying the process of
      addiction has led to unique molecular targets and strategies for
      pharmacotherapies against addiction. However, the successful translation of these
      discoveries will require: 1) a more active engagement of the pharmaceutical
      sector, 2) partnership with regulatory agencies to arrive at meaningful outcomes
      for medication approval and 3) a greater involvement of the healthcare system in
      the screening and treatment of substance use disorders.

PMID- 22157860
TI  - The role of complementary, alternative, and integrative medicine in personalized
      health care.

PMID- 22157861
TI  - Grateful DREADDs: engineered receptors reveal how neural circuits regulate
      behavior.

PMID- 22157862
TI  - Dopamine D3 receptor function and cocaine exposure.

PMID- 22157863
TI  - Methamphetamine-induced oxidation of proteins and alterations in protein
      processing.

PMID- 22157864
TI  - Chronic N-acetylcysteine after cocaine self-administration produces enduring
      reductions in drug-seeking.

PMID- 22157865
TI  - Placental source for 5-HT that tunes fetal brain development.

PMID- 22157866
TI  - Mainstreaming mice.

PMID- 22157867
TI  - Phospholipase D as a therapeutic target in brain disorders.

PMID- 22157868
TI  - Transferrin antibodies into the brain.

PMID- 22157869
TI  - Endogenous opioids as physiological antidepressants: complementary role of delta
      receptors and dopamine.

PMID- 22157870
TI  - Oxytocin as a potential therapeutic target for schizophrenia and other
      neuropsychiatric conditions.

PMID- 22157871
TI  - Dysregulation of mTOR signaling in neuropsychiatric disorders: therapeutic
      implications.

PMID- 22157872
TI  - Habenular signaling in nicotine reinforcement.

PMID- 22157873
TI  - Circuits, cells, and synapses: toward a new target for deep brain stimulation in
      depression.

PMID- 22157874
TI  - Update on corticotropin-releasing factor pharmacotherapy for psychiatric
      disorders: a revisionist view.

PMID- 22157875
TI  - Update on omega-3 polyunsaturated fatty acids in early-stage psychotic disorders.

PMID- 22157876
TI  - Beyond antipsychotics: pharmacologically-augmented cognitive therapies (PACTs)
      for schizophrenia.

PMID- 22157877
TI  - From father to offspring: paternal transmission of depressive-like behaviors.

PMID- 22157878
TI  - Effect of ankle braces on lower extremity joint energetics in single-leg
      landings.
AB  - PURPOSE: Ankle sprains are one of the most common injuries in competitive and
      recreational athletics. Studies have shown that the use of prophylactic ankle
      braces effectively reduces the frequency of ankle sprains in athletes. However,
      although it is generally accepted that the ankle braces are effective at reducing
      frontal plane motion, some researchers report that the design of the brace may
      also reduce ankle sagittal plane motion. The purpose of this study was to
      quantify lower extremity joint contributions to energy absorption during single
      legged drop landings in three ankle brace conditions (no brace, boot brace, and
      hinged brace). METHODS: Eleven physically active females experienced in landing
      and free of lower extremity injury (age = 22.3 +/- 1.7 yr, height = 1.66 +/- 0.04
      m, mass = 58.43 +/- 5.83 kg) performed 10 single-leg drop landings in three
      conditions (one unbraced, two braced) from a 0.33-m height. Measurements taken
      were hip, knee, and ankle joint impulse; hip, knee, ankle, and total work; and
      hip, knee, and ankle joint relative work. RESULTS: Total energy absorption
      remained consistent across the braced conditions (P = 0.057). Wearing the boot
      brace reduced relative ankle work (P = 0.04, Cohen d = 0.43) but did not change
      relative knee (P = 0.08, Cohen d = 0.32) or hip (P = 0.14, Cohen d = 0.20) work
      compared with the no-brace condition. CONCLUSIONS: In an ankle-braced condition,
      ankle, knee, and hip energetics may be altered depending on the design of the
      brace.

PMID- 22157879
TI  - Neural correlates of attentional and executive processing in middle-age fencers.
AB  - PURPOSE: Open-skill sports require high levels of visual attention and fast and
      flexible decision making and action execution. We evaluated whether these sports
      may counteract the well-known age-related declines in executive processing.
      METHODS: Young and middle-age fencers and nonathletes were studied. Participants
      (N = 40) performed visual motor tasks while reaction times (RTs) and event
      related potentials were recorded. RESULTS: RTs were slower for the older
      subjects, but accuracy was not impaired. At event-related potential level, the
      late P3 component was delayed in older subjects, but those who participated in
      sports showed less delay. The RTs of middle-age and young fencers were
      comparable; the P1 latency of middle-age fencers was similar to that of the
      younger subjects; the N1 was enhanced in older, as well as younger, fencers; the
      N2 component of fencers had shorter latencies and larger amplitudes than
      nonathletes; and in no-go trials, the P3 component was enhanced in fencers
      independent of age. CONCLUSIONS: Overall, the practice of open-skill sports was
      associated with improvement of the executive functions that are already degraded
      at middle age.

PMID- 22157880
TI  - Effect of exercise training modality on C-reactive protein in type 2 diabetes.
AB  - PURPOSE: Type 2 diabetes is associated with increased risk of cardiovascular
      disease and elevated C-reactive protein (CRP) levels. Aerobic exercise training
      has been shown to improve CRP; however, there are limited data evaluating the
      effect of other exercise training modalities (aerobic, resistance, or combination
      training) in individuals with type 2 diabetes. METHODS: Participants (n = 204)
      were randomized to an aerobic exercise (aerobic), resistance exercise
      (resistance), or a combination of both (combination) for 9 months. CRP was
      evaluated at baseline and at follow-up. RESULTS: Baseline CRP was correlated with
      fat mass, waist circumference, body mass index, and VO(2peak) (P < 0.05). CRP was
      not reduced after aerobic (0.16 mg.L(-1), 95% confidence interval (CI) = -1.0 to
      1.3 mg.L(-1)), resistance (-0.03 mg.L(-1), 95% CI = -1.1 to 1.0 mg.L(-1)), or
      combination (-0.49 mg.L(-1), 95% CI = -1.5 to 0.6 mg.L(-1)) training compared to
      control (0.35 mg.L(-1), 95% CI = -1.0 to 1.7 mg.L(-1)). Changes in fasting
      glucose (r = 0.20, P = 0.009), glycated hemoglobin (HbA1c) (r = 0.21, P = 0.005),
      and fat mass (r = 0.19, P = 0.016) were associated with reductions in CRP but not
      with change in fitness or weight (P > 0.05). There were significant trends
      observed for CRP among tertiles of change in HbA1c (P = 0.009) and body fat (P =
      0.040). CONCLUSIONS: Aerobic, resistance, or a combination of both did not reduce
      CRP levels in individuals with type 2 diabetes. However, exercise-related
      improvements in HbA1c, fasting glucose, and fat mass were associated with
      reductions in CRP.

PMID- 22157882
TI  - State-specific prevalence of no leisure-time physical activity among adults with
      and without doctor-diagnosed arthritis--United States, 2009.
AB  - The prevalence of no leisure-time physical activity (LTPA) among U.S. residents
      decreased from 31% in 1989 to 25% in 2002 and was still at 25% in 2008, based on
      Behavioral Risk Factor Surveillance System (BRFSS) data. Further reduction in the
      prevalence of no LTPA among all adults might be hindered by population subgroups
      that have exceptionally high rates of no LTPA, such as adults with arthritis.
      Approximately 50 million adults have arthritis, the majority of whom have
      arthritis-specific barriers to being physically active, such as pain and fear of
      making their arthritis worse. Despite the known benefits of physical activity for
      arthritis (e.g., reduced pain), persons with arthritis are more likely to report
      no LTPA. To assess state-specific prevalence of no LTPA among adults with and
      without doctor-diagnosed arthritis, CDC analyzed BRFSS data from 2009. This
      report summarizes the results of that analysis, which found that among adults
      with arthritis 1) prevalence of no LTPA is significantly higher compared with
      adults without arthritis in every state and the District of Columbia (DC), 2) the
      disparity in prevalence of no LTPA between adults with and without arthritis is
      large (median: 53% disparity gap), 3) 23 (45%) states had an age-standardized
      prevalence of no LTPA>=30.0%, and 4) adults with arthritis reporting no LTPA
      comprised a substantial proportion (median: 35.2%) of all adults reporting no
      LTPA in each state. To reduce the prevalence of no LTPA among all adults,
      physical activity promotion initiatives should include interventions such as
      targeted health communication campaigns and community-based group exercise
      programs proven safe and effective for adults with arthritis.

PMID- 22157881
TI  - Responses to exercise differ for chronic fatigue syndrome patients with
      fibromyalgia.
AB  - Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are chronic multisymptom
      illnesses with substantial clinical and diagnostic overlap. We have previously
      shown that, when controlling for aerobic fitness and accounting for comorbid FM,
      CFS patients do not exhibit abnormal cardiorespiratory responses during maximal
      aerobic exercise compared with healthy controls, despite differences in pain and
      exertion. PURPOSE: The purpose of the present study was to examine cardiac and
      perceptual responses to steady-state submaximal exercise in CFS patients and
      healthy controls. METHODS: Twenty-one CFS patients (13 CFS with comorbid FM (CFS
      + FM)) and 14 controls completed 20 min of submaximal cycling exercise. Impedance
      cardiography was used to determine cardiac responses during exercise. Systolic
      blood pressure (SBP), RPE, and leg muscle pain were also measured. Data were
      analyzed using a doubly multivariate, repeated-measures MANOVA to model the
      exercise response. RESULTS: There was a significant multivariate time-by-group
      interaction (P < 0.05). The CFS + FM group exhibited an exercise response
      characterized by higher stroke index, ventilatory equivalents for oxygen and
      carbon dioxide and RPE, lower SBP, and similar HR responses compared to controls.
      CONCLUSIONS: The present results extend on our previous work with maximal
      exercise and show that CFS and CFS + FM differ in their responses to steady-state
      exercise. These results highlight the importance of accounting for comorbid
      conditions when conducting CFS research, particularly when examining
      psychophysiological responses to exercise.

PMID- 22157883
TI  - Update: influenza activity--United States, October 2-November 26, 2011.
AB  - During October 2-November 26, 2011, influenza activity remained low in the United
      States. Thus far, influenza A viruses have predominated, and the majority are
      antigenically related to the 2011-12 influenza vaccine strains for the Northern
      Hemisphere. This report summarizes U.S. influenza activity since October 2 and
      updates the previous summary.

PMID- 22157884
TI  - Recommendations for use of an isoniazid-rifapentine regimen with direct
      observation to treat latent Mycobacterium tuberculosis infection.
AB  - Preventing tuberculosis (TB) by treating latent Mycobacterium tuberculosis
      infection (LTBI) is a cornerstone of the U.S. strategy for TB elimination. Three
      randomized controlled trials have shown that a new combination regimen of
      isoniazid (INH) and rifapentine (RPT) administered weekly for 12 weeks as
      directly observed therapy (DOT) is as effective for preventing TB as other
      regimens and is more likely to be completed than the U.S. standard regimen of 9
      months of INH daily without DOT. This report provides CDC recommendations for
      using the INH-RPT regimen. The new regimen is recommended as an equal alternative
      to the 9-month INH regimen for otherwise healthy patients aged>=12 years who have
      LTBI and factors that are predictive of TB developing (e.g., recent exposure to
      contagious TB). The new regimen also can be considered for other categories of
      patients when it offers practical advantages. Although the INH-RPT regimen was
      well tolerated in treatment trials, monitoring for adverse effects is
      recommended. Severe adverse effects should be reported to the Food and Drug
      Administration (FDA) and CDC.

PMID- 22157885
TI  - Genetic and pharmacological targeting of TPL-2 kinase ameliorates experimental
      colitis: a potential target for the treatment of Crohn's disease?
AB  - Inflammatory bowel disease is characterized by dysregulated immune responses
      against intestinal microflora leading to marked activation of nuclear factor
      kappaB (NF-kappaB) with subsequent production of pro-inflammatory cytokines.
      Besides NF-kappaB, the tumor progression locus 2 (TPL-2)/extracellular signal
      regulated kinase (ERK) pathway also regulates inflammatory cytokines such as
      interleukin-1beta and tumor necrosis factor-alpha, but its role during intestinal
      inflammation is incompletely understood. We analyzed the impact of TPL-2 in the
      dextran sulfate sodium-induced experimental colitis model. Despite normal
      activation of NF-kappaB, animals lacking TPL-2 developed only mild colitis with
      reduced synthesis of inflammatory cytokines. Further, pharmacological inhibition
      of the TPL-2 kinase was similarly effective in ameliorating colitis as TPL-2
      deficiency without obvious side effects. Because increased TPL-2/ERK activation
      was seen in patients with Crohn's disease (CD) but not ulcerative colitis, our
      findings encourage further investigation of TPL-2 kinase as potential target for
      the treatment of CD patients.

PMID- 22157886
TI  - Modeling and imaging 3-dimensional collective cell invasion.
AB  - A defining characteristic of cancer malignancy is invasion and metastasis. In
      some cancers (e.g. glioma), local invasion into surrounding healthy tissue is the
      root cause of disease and death. For other cancers (e.g. breast, lung, etc.), it
      is the process of metastasis, in which tumor cells move from a primary tumor
      mass, colonize distal sites and ultimately contribute to organ failure, that
      eventually leads to morbidity and mortality. It has been estimated that invasion
      and metastasis are responsible for 90% of cancer deaths. As a result, there has
      been intense interest in identifying the molecular processes and critical protein
      mediators of invasion and metastasis for the purposes of improving diagnosis and
      treatment. A challenge for cancer scientists is to develop invasion assays that
      sufficiently resemble the in vivo situation to enable accurate disease modeling.
      Two-dimensional cell motility assays are only informative about one aspect of
      invasion and do not take into account extracellular matrix (ECM) protein
      remodeling which is also a critical element. Recently, research has refined our
      understanding of tumor cell invasion and revealed that individual cells may move
      by elongated or rounded modes. In addition, there has been greater appreciation
      of the contribution of collective invasion, in which cells invade in strands,
      sheets and clusters, particularly in highly differentiated tumors that maintain
      epithelial characteristics, to the spread of cancer. We present a refined method
      for examining the contributions of candidate proteins to collective invasion. In
      particular, by engineering separate pools of cells to express different
      fluorescent proteins, it is possible to molecularly dissect the activities and
      proteins required in leading cells versus those required in following cells. The
      use of RNAi provides the molecular tool to experimentally disassemble the
      processes involved in individual cell invasion as well as in different positions
      of collective invasion. In this procedure, mixtures of fluorescently-labeled
      cells are plated on the bottom of a Transwell insert previously filled with
      Matrigel ECM protein, then allowed to invade "upwards" through the filter and
      into the Matrigel. Reconstruction of z-series image stacks, obtained by confocal
      imaging, into three-dimensional representations allows for visualization of
      collectively invading strands and analysis of the representation of fluorescently
      labeled cells in leading versus following positions.

PMID- 22157887
TI  - Structural insights into the activation of RIG-I, a nanosensor for viral RNAs.

PMID- 22157890
TI  - Immune cell transdifferentiation: a complex crosstalk between circulating immune
      cells and the haematopoietic niche.

PMID- 22157888
TI  - DNA methylation: TET proteins-guardians of CpG islands?
AB  - DNA methylation is involved in key cellular processes, including X-chromosome
      inactivation, imprinting and transcriptional silencing of specific genes and
      repetitive elements. DNA methylation patterns are frequently perturbed in human
      diseases such as imprinting disorders and cancer. The recent discovery that the
      three members of the TET protein family can convert 5-methylcytosine (5mC) into 5
      hydroxymethylcytosine (5hmC) has provided a potential mechanism leading to DNA
      demethylation. Moreover, the demonstration that TET2 is frequently mutated in
      haematopoietic tumours suggests that the TET proteins are important regulators of
      cellular identity. Here, we review the current knowledge regarding the function
      of the TET proteins, and discuss various mechanisms by which they contribute to
      transcriptional control. We propose that the TET proteins have an important role
      in regulating DNA methylation fidelity, and that their inactivation contributes
      to the DNA hypermethylation phenotype often observed in cancer.

PMID- 22157892
TI  - Where do you come from; where do you go? Pluripotency, differentiation and
      malfunction of stem cells.
AB  - The international conference 'Stem Cells in Development and Disease' took place
      in September 2011 at the Max-Delbruck-Center for Molecular Medicine (MDC) in
      Berlin. It brought together scientists working on different types of stem cell
      and covered the latest findings in stem cell biology, including the genetic and
      epigenetic mechanisms of reprogramming, maintenance of pluripotency and
      differentiation.

PMID- 22157893
TI  - Telomere flip-flop: an unfolding passage to senescence.

PMID- 22157895
TI  - Five dysfunctional telomeres predict onset of senescence in human cells.
AB  - Replicative senescence is accompanied by a telomere-specific DNA damage response
      (DDR). We found that DDR+ telomeres occur spontaneously in early-passage normal
      human cells and increase in number with increasing cumulative cell divisions.
      DDR+ telomeres at replicative senescence retain TRF2 and RAP1 proteins, are not
      associated with end-to-end fusions and mostly result from strand-independent,
      postreplicative dysfunction. On the basis of the calculated number of DDR+
      telomeres in G1-phase cells just before senescence and after bypassing senescence
      by inactivation of wild-type p53 function, we conclude that the accrual of five
      telomeres in G1 that are DDR+ but nonfusogenic is associated with p53-dependent
      senescence.

PMID- 22157896
TI  - Stretching beyond your comfort zone.

PMID- 22157894
TI  - Emerging roles of the FBW7 tumour suppressor in stem cell differentiation.
AB  - FBW7 is a ubiquitin E3 ligase substrate adaptor that targets many important
      oncoproteins-such as Notch, c-Myc, cyclin E and c-Jun-for ubiquitin-dependent
      proteolysis. By doing so, it plays crucial roles in many cellular processes,
      including cell cycle progression, cell growth, cellular metabolism,
      differentiation and apoptosis. Loss of FBW7 has been observed in many types of
      human cancer, and its role as a tumour suppressor was confirmed by genetic
      ablation of FBW7 in mice, which leads to the induction of tumorigenesis. How FBW7
      exerts its tumour suppression function, and whether loss of FBW7 leads to de
      differentiation or acquisition of stemness-a process frequently seen in human
      carcinomas-remains unclear. Emerging evidence shows that FBW7 controls stem cell
      self-renewal, differentiation, survival and multipotency in various stem cells,
      including those of the haematopoietic and nervous systems, liver and intestine.
      Here, we focus on the function of FBW7 in stem cell differentiation, and its
      potential relevance to human disease and therapeutics.

PMID- 22157897
TI  - Tap into electronic networking to advance your career.

PMID- 22157898
TI  - Reap the benefits of certification.

PMID- 22157899
TI  - Increasing your professional net worth: tips for new nurses.

PMID- 22157900
TI  - Explore nursing abroad! Interview by Sandy Dancer.

PMID- 22157901
TI  - Mentor and protege: a mutually beneficial relationship.

PMID- 22157902
TI  - Community health nursing: a partnership of care.

PMID- 22157903
TI  - Preparing successful grant proposals.

PMID- 22157904
TI  - Introducing the Nurse's Education Center!

PMID- 22157905
TI  - Striving for work-life balance.

PMID- 22157909
TI  - Multidisciplinary communication strategies for Magnet(r) success.

PMID- 22157910
TI  - Nomadic nursing: opportunities in travel nursing.

PMID- 22157911
TI  - Intermediate and normal sized CGG repeat on the FMR1 gene does not negatively
      affect donor ovarian response.
AB  - BACKGROUND: Fragile X syndrome is associated with low ovarian reserve and poor
      ovarian response. The aim of this study was to investigate whether CGG repeats on
      the fragile X mental retardation 1 (FMR1) gene have predictive value for ovarian
      response to stimulation with gonadotrophins and for clinical outcome in our
      oocyte donation program. METHODS: Oocyte donor candidates were selected according
      to Instituto Bernabeu oocyte donation program requirements. Fragile X genetic
      screening was performed in 204 oocyte donors, defining 141 controls and 63 cases:
      35-39 repeats (n = 34), 40-45 (n = 12) and >45 (n = 17). All the patients
      underwent ovarian stimulation using a GnRH antagonist protocol and received a
      GnRH agonist trigger. The main factors used to measure outcome were oocyte
      yields, days of stimulation, gonadotrophin dosages, biochemical pregnancy,
      ongoing pregnancy and miscarriage rates. RESULTS: No differences between the
      study group and controls were reported in oocyte yields (17.5 versus 18.9) or
      days of stimulation (11.40 versus 9.82). The control group used significantly
      more gonadotrophin (2212 versus 1850 IU) than the study group. Clinical outcome
      was not affected by the CGG repeats on the FMR1 gene in oocyte donors.
      CONCLUSIONS: No negative effect was observed for intermediate-sized CGG repeats
      on ovarian stimulation and clinical outcome using a non-confounding model of
      oocyte donation. These results disagree with previous studies performed on
      infertility patients. Owing to the present study, fragile X genetic screening
      should not be considered for prediction of response to ovarian stimulation.

PMID- 22157912
TI  - Prenatal stress, gestational age and secondary sex ratio: the sex-specific
      effects of exposure to a natural disaster in early pregnancy.
AB  - BACKGROUND: Previous research suggests that maternal exposure to acute stress has
      a negative impact on the duration of pregnancy, and that this effect may vary by
      the time of exposure. It has also been proposed that stress exposure reduces the
      ratio of male-to-female births. To date, no study has jointly examined both
      outcomes, although they may be strongly related. Using population-level data with
      no selectivity, we jointly study the sex-specific effect of stress on the
      duration of pregnancy and the observed sex ratio among pregnant women exposed to
      a major earthquake in Chile. METHODS: In a quasi-experimental design, women
      exposed to the earthquake in different months of gestation were compared with
      women pregnant 1 year earlier. Estimates from a comparison group of pregnant
      women living in areas not affected by the earthquake were also examined to rule
      out confounding trends. Regression models were used to measure the impact of
      earthquake exposure on gestational age and preterm birth by sex across month of
      gestation. A counterfactual simulation was implemented to assess the effect of
      the earthquake on the secondary sex ratio accounting for the differential impact
      of stress on gestational age by sex. RESULTS: Earthquake exposure in Months 2 and
      3 of gestation resulted in a significant decline in gestational age and increase
      in preterm delivery. Effects varied by sex, and were much larger for female than
      male pregnancies. Among females, the probability of preterm birth increased by
      0.038 [95% confidence interval (CI): 0.005, 0.072] in Month 2 and by 0.039 (95%
      CI: 0.002, 0.075) in Month 3. Comparable increases for males were insignificant
      at the conventional P < 0.05 level. After accounting for the sex-specific impact
      on gestational age, a decline in the male-to-female ratio in Month 3 of exposure
      was detected [-0.058 (95% CI: -0.113, -0.003)]. CONCLUSIONS: Maternal exposure to
      an exogenous stressor early but not late in the pregnancy affects gestational age
      and the probability of preterm birth. This effect is much stronger in females
      than males. Stress exposure in early pregnancy may also contribute to a decline
      in the ratio of male-to-female live births in exposed cohorts.

PMID- 22157914
TI  - Fixation and its role in the causation, laterality and location of pterygium: a
      study in amblyopes and non-amblyopes.
AB  - AIM: To evaluate the role of fixation in causing pterygium and determining its
      laterality and location. METHODS: This is a prospective, observational, case
      control study. Cases were defined as patients with primary pterygium who had
      unilateral amblyopia with eccentric fixation. Controls were age-matched patients
      with primary pterygium, but without amblyopia and eccentric fixation. All
      patients underwent complete ocular, orthoptic, and systemic examination and a
      detailed risk-factor assessment (latitude of residence, exposure to sunlight,
      sand, and a high-reflectance environment). The role of fixation in the causation,
      laterality and location of pterygium was evaluated. Fisher's exact test, the
      unpaired t-test, and odds ratio (OR) were carried out to determine the
      significance of the observations. RESULTS: The mean age of subjects was 47.1+/
      5.25 years in cases (n=107) and 48.2+/-4.75 years in controls (n=310; P=0.78). As
      far as known risk factors were concerned, both groups were evenly matched. Among
      the cases, 88 (82.2%) patients demonstrated suppression of the amblyopic eye and
      19 (17.8%) patients had abnormal retinal correspondence (ARC). Patients with
      suppression had a unilateral pterygium in the better (fixating) eye, whereas
      those with ARC had bilateral pterygia. Among the controls, 192 (61.9%) eyes had
      bilateral pterygia and 118 (38.1%) eyes had unilateral pterygium. In controls,
      the dominant eye had a higher prevalence of pterygium. All patients in both
      groups had a nasal pterygium. Pterygium and fixation were strongly associated
      (P=0.007; Fisher's exact test; OR -15.98; P=0.008). CONCLUSION: Fixation appears
      to have an important role in causing pterygium and determining its location and
      laterality.

PMID- 22157915
TI  - What is causing the corneal ulcer? Management strategies for unresponsive corneal
      ulceration.
AB  - Infectious keratitis represents a significant cause of ocular morbidity in the
      United States. The work-up and treatment of presumed infectious keratitis (PIK)
      has changed in the past two decades. The development of newer topical antibiotics
      has enabled broad-spectrum antibiotic coverage with good tissue penetration. The
      majority of PIK cases respond well to this strategy. The small numbers of cases
      that do not respond to the treatment are the cases that offer a diagnostic and
      therapeutic challenge. This review will describe different algorithms that can be
      followed for the successful management of patients with difficult or progressive
      PIK. These algorithms are based on scientific work and on our empirical clinical
      experience. The review will also present three different clinical cases of PIK
      that were managed according to the algorithms presented in this review.

PMID- 22157916
TI  - Visual function alterations in orbital tumors and factors predicting visual
      outcome after surgery.
AB  - PURPOSE: To study the effect of orbital tumors on visual functions and highlight
      the factors predictive of visual outcome after surgery. METHODS: A prospective
      interventional study compared visual function parameters and fundus changes,
      before and after surgery, in eyes having well-defined orbital tumors with the
      normal fellow eye. These included visual acuity (VA), refractive error,
      keratometry changes, color vision, Goldmann visual field (GVF), and visual evoked
      response (VER). RESULTS: In total 28 cases (age range 7-56 years), of which the
      majority of tumors were vascular (46%) and lacrimal (18%) in origin, had a mean
      VA of 0.54+/-0.33 in the affected eye, which improved postoperatively to 0.66+/
      0.31 (P=0.002). The affected eye had a median refractive error of +0.00 DS (-2.00
      to 5.13), which was significantly more hyperopic than the normal eye (median
      +0.00 DS; range -1.25 to +1.63 DS) and normalized postoperatively. Keratometry
      showed higher astigmatism in the involved eye (P=0.004). The fundus showed disc
      pallor, edema, and/or choroidal folds, of which disc edema resolved in all cases
      after surgery. In all, 40% of the affected eyes had a deficient color vision and
      this partially improved postoperatively (P=0.25). GVF had abnormalities in 10
      cases, half of which normalized postoperatively (P=0.04). The VER of affected
      eyes had a mean amplitude of 8.91+/-4.59 MUv and latency of 116.3+/-14.7 ms, with
      improvement after surgery (P=0.005 and 0.001, respectively). CONCLUSION: Orbital
      tumors adversely affected visual functions. The presenting acuity depended on
      disc changes, color vision abnormalities, and prolonged VER latency. The
      postoperative VA depended on VA at presentation, amount of proptosis, degree of
      hyperopia, and clinically significant VER abnormalities.

PMID- 22157917
TI  - Prevalence and risk factors for primary open-angle glaucoma in a rural northeast
      China population: a population-based survey in Bin County, Harbin.
AB  - PURPOSE: To estimate the prevalence and associated risk factors of primary open
      angle glaucoma (POAG) in a rural population in northeast China. METHODS: A
      population-based survey was conducted within Bin County, Harbin of northeast
      China. Glaucoma was diagnosed using International Society of Geographical and
      Epidemiological Ophthalmology criteria. All the subjects underwent a complete
      ophthalmic examination. RESULTS: A total of 4956 (86.0%) of 5762 subjects aged 40
      years or older were examined. The mean intraocular pressure (IOP) of right eyes
      was 14.0 (95% confidence interval (CI), 13.9 to 14.1) mm Hg. The prevalence of
      POAG was 0.71% (35/4956, 95% CI, 0.47 to 0.93). In these POAG subjects, 17
      (48.6%) had elevated IOP >21 mm Hg in either eye, 3 (8.8%) participants had been
      treated by laser trabeculoplasty or trabeculectomy and were known to have POAG.
      Vision impairment to varying degrees was present in 20 subjects (58.8%) with 1
      subject blind in both eyes and 8 subjects blind in one eye. On multivariate
      analysis, age, family history of glaucoma, systemic hypertension, and IOP were
      regarded as significant independent risk factors. CONCLUSIONS: POAG is a disease
      of serious consequence and of low diagnosis and treatment rates in rural
      northeast China. Age, family history of glaucoma, systemic hypertension, and IOP
      remain as significant independent risk factors for POAG.

PMID- 22157918
TI  - Silicone oil removal after rhegmatogenous retinal detachment: comparing
      techniques.
AB  - PURPOSE: To assess the outcome of silicone oil removal after rhegmatogenous
      retinal detachment (RRD) surgery, and to compare results of a two-port (infusion
      extraction) versus a three-port (full vitrectomy) approach. METHODS: Primary
      outcome measure was the rate of redetachment. Secondary outcome measures were
      visual acuity, rate of intraoperative and postoperative epiretinal membrane
      removal and complications. RESULTS: We included 147 consecutive cases. There were
      15 cases of giant retinal tear, 26 cases of RRD without proliferative
      vitreoretinopathy (PVR) and 106 cases of RRD with PVR. The overall redetachment
      rate after silicone oil removal was 17.7%. In the group treated with the two-port
      technique (n=95), the retina redetached in 16 cases (16.8%), and in the group
      treated with the three-port technique (n=52), redetachment occurred in 10 cases
      (19.2%). This difference was not statistically significant (P=0.717; chi (2)
      test). There was a significantly higher redetachment rate in cases with a short
      oil tamponade duration of <2 months. CONCLUSION: We reconfirm a relatively high
      redetachment rate after silicone oil removal. The risk of redetachment is not
      lower with the three-port compared with the two-port approach.

PMID- 22157919
TI  - Multidisciplinary management of periocular necrotising fasciitis: a series of 11
      patients.
AB  - BACKGROUND: Necrotising fasciitis is an uncommon but life-threatening soft tissue
      infection characterised by rapidly spreading inflammation and necrosis of skin,
      subcutaneous fat and fascia. Left untreated, the mortality can be more than 70%.
      Early surgical intervention can reduce morbidity and mortality. PATIENTS AND
      METHODS: This is a series of 11 patients who presented to our oculoplastic and
      orbit unit with periocular necrotising fasciitis over a period of five years. We
      present the modes of presentation, predisposing factors, diagnosis, and the
      multidisciplinary team management of these patients. RESULTS: Of the 11 patients,
      1 patient died and 2 patients required intensive care management. Of the 10
      surviving patients, 8 patients needed further surgical interventions for
      correction of complications, like eyelid malposition, ptosis and protective or
      corrective surgery in the form of ectropion correction, skin grafting and other
      rehabilitative procedures. CONCLUSION: To the best of our knowledge, this is the
      largest series of periocular necrotising fasciitis in the literature. Necrotising
      fasciitis is a potentially fatal condition, resulting in a high rate of mortality
      and morbidity. Early surgical intervention reduces the mortality. A high index of
      suspicion is needed to make a prompt diagnosis. These patients need expeditious
      intervention and may require a long follow-up and subsequent surgery for
      complications related to scarring and other sequelae.

PMID- 22157920
TI  - Orbital decompression for Graves' orbitopathy in England.
AB  - AIMS: The purpose of this study was to obtain data on orbital decompression
      procedures performed in England, classed by hospital and locality, to evaluate
      regional variation in care. METHODS: Data on orbital decompression taking place
      in England over a 2-year period between 2007 and 2009 were derived from CHKS Ltd
      and analysed by the hospital and primary care trust. RESULTS AND CONCLUSIONS: In
      all, 44% of these operations took place in hospitals with an annual workload of
      10 or fewer procedures. Analysis of the same data by primary care trust suggests
      an almost 30-fold variance in the rates of decompression performed per unit
      population. Expertise available to patients with Graves' orbitopathy and rates of
      referral for specialist care in England appears to vary significantly by
      geographic location. These data, along with other outcome measures, will provide
      a baseline by which progress can be judged.

PMID- 22157921
TI  - Refeeding syndrome in children in developing countries who have celiac disease.
AB  - OBJECTIVES: The clinical presentations of celiac crisis and refeeding syndrome in
      celiac disease are almost similar, but information about refeeding syndrome is
      scarce. We are reporting for the first time 5 cases of refeeding syndrome in
      children with celiac disease that could have otherwise been labeled as celiac
      crisis. METHODS: From January to December 2010, a chart review of hospital
      records of all celiac disease cases was performed, and refeeding syndrome was
      ascribed in those celiac patients who deteriorated clinically after initiation of
      a gluten-free diet and had biochemical parameters suggestive of refeeding
      syndrome such as hypophosphatemia, hypokalemia, hypocalcemia, and
      hypoalbuminemia. RESULTS: Of the total 35 celiac disease patients, 5 (median age
      6.5 [range 2.2-10] years, 3 boys) were identified as having refeeding syndrome.
      All 5 children were severely malnourished (body mass index <14 kg/m) and all of
      them had anemia, hypophosphatemia, hypokalemia, hypoalbuminemia, and
      hypocalcemia, meaning that they had the perfect setting for developing refeeding
      syndrome. At the same time, their clinical features fulfilled the criteria for
      celiac crisis except that their symptoms have worsened after the introduction of
      a gluten-free diet. Nevertheless, instead of using steroids, they were managed as
      refeeding syndrome in terms of correction of electrolytes and gradual feeding,
      and that led to a successful outcome in all of them. CONCLUSIONS: Severely
      malnourished patients with celiac disease are at risk of developing potentially
      life-threatening refeeding syndrome, which may mimic celiac crisis, especially in
      developing countries. Early recognition and appropriate treatment are the keys to
      a successful outcome.

PMID- 22157922
TI  - Transcriptional basis for hepatic fibrosis in cystic fibrosis-associated liver
      disease.
AB  - OBJECTIVES: Liver disease contributes to significant morbidity and mortality in
      cystic fibrosis (CF). Although all patients with CF express the defective CF
      transmembrane conductance regulator in cholangiocytes, many develop asymptomatic
      fibrosing liver disease. Only some develop cirrhosis, with pathogenesis remaining
      enigmatic. Available noninvasive diagnostic tools do not identify patients at
      risk before development of advanced fibrosis. We conducted a pilot study to
      identify genes associated with hepatic injury and fibrosis on liver biopsy that
      may help elucidate determinants of CF-associated liver disease (CFLD). METHODS:
      Liver tissue from children with CFLD with various stages of hepatic fibrosis was
      compared with pediatric controls using cDNA array analysis. Differential
      expression of genes of interest was then assessed relative to pediatric control
      liver and non-CF cholestatic disease control liver from patients with biliary
      atresia, using both real-time reverse transcription-polymerase chain reaction and
      immunohistochemistry. RESULTS: cDNA array demonstrated differential expression of
      numerous genes associated with hepatic fibrogenesis including collagens, matrix
      metalloproteinases, and chemokines in CFLD versus normal controls, particularly
      decreased expression in tissue remodeling genes including plasminogen activator
      inhibitor-1 (PAI-1, up to 25-fold) and tissue inhibitor of metalloproteinase-1
      (TIMP-1); this was validated by real-time reverse transcription-polymerase chain
      reaction (PAI-1, P = 0.004; TIMP-1, P = 0.019). No significant decrease in PAI-1
      or TIMP-1 mRNA was observed in biliary atresia versus normal control.
      Immunohistochemistry confirmed the decreased expression of hepatic PAI-1 and TIMP
      1 protein in CFLD versus both normal and biliary atresia disease controls.
      CONCLUSIONS: The coordinated differential expression of these genes associated
      with liver fibrosis provides evidence for a transcriptional basis for the
      pathogenesis of CFLD and provides avenues for further study. Clarifying the
      pathogenesis of CFLD will facilitate techniques for early, precirrhotic detection
      and targeted interventions.

PMID- 22157923
TI  - Expression of acid-sensing ion channels of gastric mucosa from patients with
      Henoch-Schonlein purpura.
AB  - Acid-sensing ion channels (ASICs) are members of the voltage-insensitive,
      amiloride-sensitive degenerin/epithelial Na channel family of cation channels and
      have been shown to mediate pain associated with tissue acidosis after
      inflammation or injury; however, the expression and role of ASICs in
      gastrointestinal tract of Henoch-Schonlein purpura (HSP) patients were still
      uncertain. The present study was designed to examine the expression and
      localization of ASICs in gastric mucosa from patients with HSP using
      immunochemical techniques. The results showed that there was a significant
      increase in the mean relative optical density of ASIC2 and ASIC3 but not ASIC1a
      in the lining epithelium and glandular tubes of gastric mucosa from HSP patients
      with HSP. This finding suggested that ASICs may be related to the pathogenesis of
      gastrointestinal manifestations in patients with HSP.

PMID- 22157926
TI  - Granular cell tumor of the esophagus in an adolescent girl.

PMID- 22157924
TI  - LPIN1 rs13412852 polymorphism in pediatric nonalcoholic fatty liver disease.
AB  - OBJECTIVES: The aim of the present study was to evaluate whether the lipin1
      rs13412852 C>T polymorphism is associated with nonalcoholic steatohepatitis and
      fibrosis in pediatric Italian patients with nonalcoholic fatty liver disease
      (NAFLD). METHODS: A total of 142 untreated, consecutive children and 115 adults
      with biopsy-proven NAFLD and 337 healthy controls without steatosis were studied.
      Liver histology was assessed by the NAFLD activity score and the rs13412852
      polymorphism by a 5' nuclease Taqman assay. RESULTS: Homozygosity for the
      rs13412852 T allele was underrepresented in pediatric, but not adult, patients
      with NAFLD compared with healthy controls (7% vs 14%; odds ratio [OR] 0.58, 95%
      confidence interval [CI] 0.35-0.91), and it was associated with lower
      triglycerides both in pediatric patients and healthy controls (P <= 0.01).
      Affected children carrying the rs13412852 TT genotype had a trend for a lower
      prevalence of nonalcoholic steatohepatitis, and significantly less severe liver
      damage, as indicated by NAFLD activity score severity (P = 0.026) and a lower
      prevalence of liver fibrosis (P = 0.012). The negative association between
      rs13412852 TT genotype and fibrosis was independent of Patatin-like phospholipase
      domain-containing-3 genotype and other clinical risk factors, including age,
      waist circumference, the presence of hyperglycemia, and alanine transaminase
      levels (OR 0.29; 95% CI 0.11-0.66), and it was confirmed at multivariate analysis
      in adults (OR 0.15; 95% CI 0.02-0.67). CONCLUSIONS: Lipin1 rs13412852 single
      nucleotide polymorphism is associated with the severity of liver damage and
      fibrosis progression in pediatric patients with histological NAFLD.

PMID- 22157927
TI  - Resolution of parenteral nutrition-associated jaundice on changing from a soybean
      oil emulsion to a complex mixed-lipid emulsion.
AB  - BACKGROUND AND OBJECTIVE: Resolution of parenteral nutrition (PN)-associated
      jaundice has been reported in children given a reduced dose of intravenous fat
      using a fish oil-derived lipid emulsion. The aim of the present study was to
      examine the effect on PN-associated jaundice of changing from a soybean oil
      derived lipid to a mixed lipid emulsion derived from soybean, coconut, olive, and
      fish oils without reducing the total amount of lipid given. METHODS:
      Retrospective cohort comparison examining serum bilirubin during 6 months in
      children with PN-associated jaundice who changed to SMOFlipid (n=8) or remained
      on Intralipid (n=9). RESULTS: At entry, both groups received most of their energy
      as PN (SMOFlipid 81.5%, range 65.5-100 vs Intralipid 92.2%, range 60.3-100;
      P=0.37). After 6 months, both tolerated increased enteral feeding but still
      received large proportions of their energy as PN (SMOFlipid 68.4%, range 36.6-100
      vs Intralipid 50%, range 37.6-76; P=0.15). The median bilirubin at the outset was
      143 MUmol/L (range 71-275) in the SMOFlipid group and 91 MUmol/L (range 78-176)
      in the Intralipid group. After 6 months, 5 of 8 children in the SMOFlipid and 2
      of 9 children in the Intralipid group had total resolution of jaundice. The
      median bilirubin fell by 99 MUmol/L in the SMOFlipid group but increased by 79
      MUmol/L in the Intralipid group (P=0.02). CONCLUSIONS: SMOFlipid may have
      important protective properties for the liver and may constitute a significant
      advance in PN formulation. Randomised trials are needed to study the efficacy of
      SMOFlipid in preventing PN liver disease.

PMID- 22157928
TI  - Increased pancreatic fat fraction is present in obese adolescents with metabolic
      syndrome.
AB  - OBJECTIVES: Little is known about pancreatic fat accumulation and its possible
      associations with metabolic syndrome (MetS) and glucose metabolism. The aim of
      the present study was to quantify pancreatic fat fraction (PFF) in lean and obese
      adolescents and explore its relation to metabolic parameters. METHODS: We
      recruited 25 lean and 24 obese adolescents. PFF and visceral adipose tissue (VAT)
      were determined using magnetic resonance imaging. We measured blood pressure,
      fasting glucose, insulin, liver enzymes, leptin, and lipid levels. Obese subjects
      underwent an oral glucose tolerance test. RESULTS: PFF was significantly higher
      in obese than in lean subjects (4.8+/-1.2 vs 3.6+/-0.9; P<0.001) and was
      associated with VAT, gamma-glutamyltransferase, triglycerides, high-density
      lipoprotein cholesterol, leptin concentrations, and MetS (P<0.05 for all). None
      of the obese subjects had glucose intolerance, but when adjusted for VAT, the
      following 3 parameters correlated negatively with PFF: fasting and 30- minute and
      120-minute insulin levels. We divided subjects into 3 groups: group I, lean
      without MetS; group II, obese without MetS; and group III, obese with MetS, and
      observed that PFF increased gradually among groups (I: 3.56%+/-0.88%; II: 4.70%+/
      1.06%; III: 5.34%+/-1.49%; P<0.001). CONCLUSIONS: Obese adolescents accumulate
      fat in the pancreas. PFF correlates with the presence of MetS. Even in the
      absence of glucose intolerance, pancreatic fat deposition is associated with
      impaired insulin response to glucose overload. This suggests that beta-cell
      dysfunction may already be present in nondiabetic obese adolescents, mirroring
      what has been shown in adults, and that pancreatic fat accumulation may
      participate in obesity-associated pancreatic endocrine dysfunction.

PMID- 22157929
TI  - Ketamine with and without midazolam for gastrointestinal endoscopies in children.
AB  - OBJECTIVES: Numerous publications on sedation of and anaesthesia for diagnostic
      procedures in children prove that no ideal scheme is available. Therefore, we
      decided to study the protocol with midazolam and ketamine used by
      nonanaesthetists at our institution. The study aimed to establish the lowest
      effective starting dose of ketamine and to estimate a difference in the frequency
      of adverse reactions with or without the use of midazolam as premedication, with
      special stress on emergence reactions. METHODS: During 1 year we prospectively
      randomised children scheduled for gastrointestinal endoscopies to a first group
      with and to a second group without midazolam premedication. The starting ketamine
      dose was increased until the appropriate dissociative state was reached.
      Physiological functions were closely monitored and adverse reactions noted.
      RESULTS: The median age of 201 analysed patients (111 girls, 90 boys) was 8.2
      years. The median starting dose of ketamine was 0.97 mg/kg (the group with
      midazolam premedication) and 0.99 mg/kg TT (without midazolam premedication).
      Laryngospasm was observed in 6 patients without statistical difference between
      the 2 groups. All of the adverse reactions were short lasting; they resolved by
      symptomatic treatment without complications. Emergence reactions during the
      observation period at the hospital occurred more often in the group sedated with
      ketamine without midazolam premedication (P=0.02). CONCLUSIONS: : The sedation
      protocol with ketamine is safe and efficient. The starting dose of ketamine
      should be at least 1 mg/kg. There is an advantage to the use of midazolam as
      premedication before ketamine in paediatric patients because the frequency of
      emergence reactions in hospital was reduced compared with sole ketamine use.

PMID- 22157930
TI  - Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell
      carcinoma development and frequently coexists with PIK3CA mutations.
AB  - ARID1A is a recently identified tumor suppressor gene that is mutated in ~50% of
      ovarian clear-cell carcinomas. This mutation is associated with loss of ARID1A
      protein expression as assessed by immunohistochemistry. The present study aimed
      at determining the timing of the loss of ARID1A protein expression during the
      development of ovarian clear-cell carcinoma and assessing its relevance in
      correlation to PIK3CA gene mutations. A total of 42 clear-cell carcinoma cases
      with adjacent putative precursor lesions (endometriosis-associated carcinoma
      cases (n=28) and (clear-cell) adenofibroma-associated carcinoma cases (n=14))
      were selected and subjected to immunohistochemical analysis for ARID1A protein
      expression and direct genomic DNA sequencing of exons 9 and 20 of the PIK3CA
      gene. ARID1A immunoreactivity was deficient in 17 (61%) of the 28 endometriosis
      associated carcinomas and 6 (43%) of the 14 adenofibroma-associated carcinomas.
      Among the precursor lesions adjacent to the 23 ARID1A-deficient carcinomas, 86%
      of the non-atypical endometriosis (12 of 14) and 100% of the atypical
      endometriosis (14 of 14), benign (3 of 3), and borderline (6 of 6) clear-cell
      adenofibroma components were found to be ARID1A deficient. In contrast, in the 19
      patients with ARID1A-intact carcinomas, all of the adjacent precursor lesions
      retained ARID1A expression regardless of their types and cytological atypia.
      Analysis of 22 solitary endometrioses and 10 endometrioses distant from ARID1A
      deficient carcinomas showed that all of these lesions were diffusely
      immunoreactive for ARID1A. Among the 42 clear-cell carcinomas, somatic mutations
      of PIK3CA were detected in 17 (40%) tumors and majority (71%) of these were
      ARID1A-deficient carcinomas. These results suggest that loss of ARID1A protein
      expression occurs as a very early event in ovarian clear-cell carcinoma
      development, similar to the pattern of PIK3CA mutation recently reported by our
      group, and frequently coexists (not mutually exclusive) with PIK3CA mutations.

PMID- 22157931
TI  - EGFR and KRAS mutation analysis in cytologic samples of lung adenocarcinoma
      enabled by laser capture microdissection.
AB  - The discovery of activating mutations in EGFR and KRAS in a subset of lung
      adenocarcinomas was a major advance in our understanding of lung adenocarcinoma
      biology, and has led to groundbreaking studies that have demonstrated the
      efficacy of tyrosine kinase inhibitor therapy. Fine-needle aspirates and other
      cytologic procedures have become increasingly popular for obtaining diagnostic
      material in lung carcinomas. However, frequently the small amount of material or
      sparseness of tumor cells obtained from cytologic preparations limit the number
      of specialized studies, such as mutation analysis, that can be performed. In this
      study we used laser capture microdissection to isolate small numbers of tumor
      cells to assess for EGFR and KRAS mutations from cell block sections of 19
      cytology samples from patients with known lung adenocarcinomas. We compared our
      results with previous molecular assays that had been performed on either surgical
      or cytology specimens as part of the patient's initial clinical work-up. Not only
      were we able to detect the identical EGFR or KRAS mutation that was present in
      the patient's prior molecular assay in every case, but we were also able to
      consistently detect the mutation from as few as 50 microdissected tumor cells.
      Furthermore, isolating a more pure population of tumor cells resulted in
      increased sensitivity of mutation detection as we were able to detect mutations
      from laser capture microdissection-enriched cases where the tumor load was low
      and traditional methods of whole slide scraping failed. Therefore, this method
      can not only significantly increase the number of lung adenocarcinoma patients
      that can be screened for EGFR and KRAS mutations, but can also facilitate the use
      of cytologic samples in the newly emerging field of molecular-based personalized
      therapies.

PMID- 22157932
TI  - Secretory breast carcinoma: a clinicopathological and immunophenotypic study of
      15 cases with a review of the literature.
AB  - Secretory breast carcinoma is a rare breast cancer with indolent clinical
      behavior. Recent research showed that secretory breast carcinoma belongs to the
      phenotypic spectrum of basal-like breast carcinomas. In this study, a
      clinicopathological and immunophenotypic analysis of secretory breast carcinomas
      from 15 Chinese patients was conducted. This patient group consisted of 2 males
      and 13 females, with ages ranging from 10 to 67 years old (median, 36 years old).
      All patients presented with a painless and firm mass. Tumor size ranged from 10
      to 55 mm. Most tumors were located in the outer upper quadrant of the breast. Two
      patients (2 of 13, 15%) displayed positive axillary lymph nodes. At the
      microscopic level, the presence of intracellular and extracellular secretory
      material was the most remarkable feature. Most cases showed mild dysplasia
      cytologically. All cases were negative for estrogen receptor, progesterone
      receptor and HER2. The expression rate of the basal-like marker (CK5/6 or
      epidermal growth factor receptor) was 87% (13 of 15). The basal-like phenotype
      was identified in 13 cases (87%). Follow-up time ranged from 10 to 55 months
      (median, 19 months). None of the cases had evidence of recurrence and metastasis.
      Our study reveals that secretory breast carcinoma is a distinct subset of
      invasive breast carcinoma, with expression of basal-like markers. It should be
      noted that secretory breast carcinoma is different from conventional basal-like
      breast carcinomas. Future studies are required to further understand the
      prognostic significance of the basal-like markers expression in secretory breast
      carcinomas.

PMID- 22157933
TI  - Detection of human papilloma virus and p16 expression in high-grade adenoid
      cystic carcinoma of the head and neck.
AB  - Squamous cell carcinoma of the head and neck, particularly basaloid squamous cell
      carcinoma, may be difficult to distinguish from high-grade adenoid cystic
      carcinoma. Evidence of human papilloma virus (HPV) infection, particularly HPV
      16, is frequently found in non-keratinizing oropharyngeal squamous cell
      carcinoma. Immunoreactivity for p16, a surrogate marker for HPV infection, often
      parallels the HPV infection status in oropharyngeal squamous cell carcinoma.
      However, the incidence and correlation between p16 expression and HPV infection
      in high-grade adenoid cystic carcinoma is unknown. Sixteen cases of high-grade
      adenoid cystic carcinoma, three cases of dedifferentiated adenoid cystic
      carcinoma and eight cases of low-/intermediate-grade adenoid cystic carcinoma
      were identified for inclusion in the study. All cases were tested by
      immunohistochemistry for p16 expression and in situ hybridization for high- and
      low-risk HPV. Eight cases (100%) of low-to-intermediate-grade adenoid cystic
      carcinoma were focally positive for p16, all of which were negative for HPV. In
      all, 14 of 16 cases (88%) of high-grade adenoid cystic carcinoma and three cases
      (100%) of dedifferentiated adenoid cystic carcinoma were positive for p16; strong
      and diffuse staining was noted in three cases (3 of 19, 16%). Two cases (11%) of
      high-grade adenoid cystic carcinoma, which were also diffusely positive for p16,
      showed the presence of high-risk HPV. These findings suggest that the presence of
      HPV infection in high-grade adenoid cystic carcinoma is infrequent, even in the
      presence of p16 immunostaining. Nevertheless, HPV positivity should not be used
      to exclude the possibility of high-grade adenoid cystic carcinoma when the
      differential diagnosis includes squamous cell carcinoma. Moreover, although p16
      overexpression is often used as a surrogate marker for HPV in squamous cell
      carcinoma, it cannot be used in this manner in high-grade adenoid cystic
      carcinoma.

PMID- 22157934
TI  - Embryonal rhabdomyosarcoma of the uterine cervix: a report of 14 cases and a
      discussion of its unusual clinicopathological associations.
AB  - Embryonal rhabdomyosarcoma of the uterine cervix is an uncommon presentation of
      the most common soft-tissue sarcoma in the first decades of life. Unlike
      embryonal rhabdomyosarcoma in other anatomic sites, in which 70-80% of cases
      present before 9 years of age, the average age in our series of 14 cervical cases
      was 12.4 years (median, 13 years), with an age range of 9 months to 32 years at
      diagnosis. Of the 14 cases, 12 presented as a polyp at the cervical os; two
      patients had an infiltrative mass in the cervix without a botryoid polyp. The
      polyps measured 1.5-5 cm and all had the histopathological pattern of the sarcoma
      botryoides variant of embryonal rhabdomyosarcoma, with condensations of primitive
      and differentiated rhabdomyoblasts beneath the surface epithelium and around
      endocervical glands. Nodules of benign-appearing cartilage were present in the
      stroma of six cases (43%). One of the embyronal rhabdomyosarcomas from the
      youngest patient, 9 months old, also had a distinctive microscopic focus of
      immature tubular profiles in a primitive stroma; these tubules expressed
      epithelial and neuroendocrine markers. Two patients had a pleuropulmonary
      blastoma, one diagnosed 9 years before the embryonal rhabdomyosarcoma of the
      cervix and the other recognized synchronously. This latter 9-year old had a
      DICER1 germline mutation. One patient presented with hirsutism and had a Sertoli
      Leydig cell tumor, an incidentally detected cervical embryonal rhabdomyosarcoma,
      and nodular hyperplasia of the thyroid. Although a pleuropulmonary blastoma was
      not documented in the latter patient, ovarian sex-cord stromal tumors and nodular
      hyperplasia of the thyroid are manifestations of the pleuropulmonary blastoma
      family tumor and dysplasia syndrome (OMIM 601200). Embryonal rhabdomyosarcoma of
      the cervix must be distinguished from other rare entities, including
      adenosarcoma, malignant mixed Mullerian tumor and low-grade stromal sarcoma, as
      the former has a better prognosis; 12 of our 14 patients remain disease-free
      following conservative surgery and chemotherapy. Our study suggests that cervical
      embryonal rhabdomyosarcoma may be another pathological manifestation in the
      spectrum of extrapulmonary pathology in the setting of pleuropulmonary blastoma.

PMID- 22157935
TI  - The new molecular markers DDIT3, STT3A, ARG2 and FAM129A are not useful in
      diagnosing thyroid follicular tumors.
AB  - Preoperative characterization of thyroid follicular lesions is challenging. Fine
      needle aspiration specimens cannot differentiate follicular carcinomas from
      benign follicular neoplasias. Recently, promising markers have been detected
      using modern molecular techniques. We conducted a retrospective study to confirm
      the usefulness of immunohistochemical staining for the protein markers, DDIT3,
      STT3A (ITM1), ARG2 and FAM129A (C1orf24) in separating benign and malignant
      thyroid follicular lesions. Formalin-fixed, paraffin-embedded thyroid tissue from
      30 in-house cases (15 follicular carcinomas and 15 follicular adenomas), as well
      as 8 follicular carcinomas and 21 follicular adenomas on tissue microarray slides
      were stained immunohistochemically for DDIT3, STT3A, ARG2 and FAM129A expression.
      Control tissue consisted of thyroid parenchyma adjacent to the tumors and 11
      separate cases of normal thyroid parenchyma. All in-house cases of follicular
      adenomas, follicular carcinomas and adjacent normal thyroid tissue showed
      positive immunostaining with anti-DDIT3 and anti-STT3A. Anti-ARG2 and anti
      FAM129A polyclonal antibodies showed positive staining in 20 and 60% of in-house
      follicular adenomas, and 40 and 87% of in-house follicular carcinomas,
      respectively. Monoclonal anti-FAM129A demonstrated positive staining in 13 and
      33% of in-house follicular adenomas and follicular carcinomas, respectively.
      Polyclonal anti-DDIT3, -STT3A and -FAM129A antibodies showed positive staining in
      all tissue microarray slides of follicular carcinoma and in 76, 85 and 81% of the
      follicular adenomas, respectively. Monoclonal anti-STT3A stained 81% of the
      follicular adenoma cores. Anti-ARG2 stained positive in 13% of follicular
      carcinomas and 10% of follicular adenomas on the tissue microarray slides. In
      conclusion, DDIT3, STT3A, ARG2 and FAM129A immunohistochemistry does not appear
      to be useful in the diagnosis of thyroid follicular neoplasias, as they do not
      reliably distinguish follicular thyroid carcinoma from follicular thyroid
      adenoma.

PMID- 22157937
TI  - Prostate cancer: Prostate size can predict upgrading.

PMID- 22157936
TI  - Mixed versus pure variants of desmoplastic melanoma: a genetic and
      immunohistochemical appraisal.
AB  - Desmoplastic melanoma is subclassified into pure and mixed variants with a higher
      rate of lymph node metastasis in the latter. Given that reasons for these
      biological differences are not currently known, we investigated these subtypes
      with techniques that included genetic and immunohistochemical analyses of 43
      cases of desmoplastic melanoma (24 pure, 19 mixed). Direct DNA sequencing was
      performed on BRAFV600E, RET gene (coding region on exon 11) and KIT (exons 11, 13
      and 17). Immunohistochemical stains were performed with antibodies to markers of
      significance with respect to biological potential of nevomelanocytic
      proliferations and/or desmoplastic melanoma (Ki-67, CD117, nestin, clusterin,
      SOX10 and CD271/p75NTR). Polymorphism at the RET coding region (RETp) was noted
      in 33% of pure (8/24 cases) versus 24% of mixed (4/17 cases); BRAFV600E was
      absent in all cases of pure (0/24 cases) versus 6% of mixed (1/17 cases); no
      mutations were found in any of the cases on analyses of exons 11, 13 and 17 of
      the c-KIT gene (P=NS for all). For immunohistochemical analyses of pure versus
      mixed: mean percentage of Ki-67 nuclear positivity was 5% (s.d.=5.6) versus 28%
      (s.d.=12.6, P<0.001); CD117 stained 26% (6/23 cases) versus 78% (14/18 cases,
      P<0.01); nestin stained 83% (n=19/23 cases) versus 89% (16/18 cases, P=NS);
      clusterin stained 4% (1/23 cases) versus 6% (1/18 cases, P=NS); SOX10 87% (20/23
      cases) versus 94% (17/18 cases, P=NS) and CD271 stained 61% (14/23 cases) versus
      67% (12/18 cases, P=NS). Increased CD117 staining in the mixed variant suggests
      that alterations in the KIT protein may be involved in tumor progression. In
      addition, the proliferative index of the mixed variant was higher than that of
      the pure variant.

PMID- 22157938
TI  - Prostate cancer: Thrombospondin-1 in hypoxic vicious cycle.

PMID- 22157939
TI  - Prostate cancer: PET-CT for pelvic node staging.

PMID- 22157941
TI  - What's new in Shock, January 2012?

PMID- 22157940
TI  - Etiology and management of genitourinary tuberculosis.
AB  - Genitourinary tuberculosis (GUTB) is the second most common form of
      extrapulmonary tuberculosis, with more than 90% of cases occurring in developing
      countries. Postmortem studies--from before anti-TB therapy was available--have
      provided insight into the prevalence and natural history of the disease. In GUTB,
      the kidneys are the most common sites of infection and are infected through
      hematogenous spread of the bacilli, which then spread through the renal and
      genital tract. Diagnosis of TB is often delayed owing to the nonspecific nature
      of its presentation; therefore, a high degree of suspicion should be exercised
      and a systematic approach should be taken during investigation. Appropriate
      culture samples should be obtained to tailor treatment. Standard treatment should
      be administered for 6 months; quadruple therapy for 2 months and dual therapy for
      4 months. However, additional drugs and prolonged treatment are required if drug
      resistance occurs. Although the role of surgery in GUTB has decreased since the
      advent of anti-TB therapy, it can still have a role as an adjunct to drug
      treatment. Today, the challenges of GUTB and other forms of TB include increasing
      rates of drug-resistant cases and co-infection with HIV.

PMID- 22157942
TI  - Hyperoxia during septic shock--Dr. Jekyll or Mr. Hyde?

PMID- 22157943
TI  - What is the role for the inflammasome in burn injury and sepsis?

PMID- 22157944
TI  - The many faces of MeCP2.

PMID- 22157945
TI  - Association of mu-opioid and NMDA receptors in the periaqueductal gray: what does
      it mean for pain control?

PMID- 22157946
TI  - Expanding our understanding of neurobiological mechanisms of resilience by using
      animal models.

PMID- 22157947
TI  - Gestational methylazoxymethanol acetate administration alters proteomic and
      metabolomic markers of hippocampal glutamatergic transmission.

PMID- 22157949
TI  - Robotics and dynamic image analysis for studies of gene expression in plant
      tissues.
AB  - Gene expression in plant tissues is typically studied by destructive extraction
      of compounds from plant tissues for in vitro analyses. The methods presented here
      utilize the green fluorescent protein (gfp) gene for continual monitoring of gene
      expression in the same pieces of tissues, over time. The gfp gene was placed
      under regulatory control of different promoters and introduced into lima bean
      cotyledonary tissues via particle bombardment. Cotyledons were then placed on a
      robotic image collection system, which consisted of a fluorescence dissecting
      microscope with a digital camera and a 2-dimensional robotics platform custom
      designed to allow secure attachment of culture dishes. Images were collected from
      cotyledonary tissues every hour for 100 hours to generate expression profiles for
      each promoter. Each collected series of 100 images was first subjected to manual
      image alignment using ImageReady to make certain that GFP-expressing foci were
      consistently retained within selected fields of analysis. Specific regions of the
      series measuring 300 x 400 pixels, were then selected for further analysis to
      provide GFP Intensity measurements using ImageJ software. Batch images were
      separated into the red, green and blue channels and GFP-expressing areas were
      identified using the threshold feature of ImageJ. After subtracting the
      background fluorescence (subtraction of gray values of non-expressing pixels from
      every pixel) in the respective red and green channels, GFP intensity was
      calculated by multiplying the mean grayscale value per pixel by the total number
      of GFP-expressing pixels in each channel, and then adding those values for both
      the red and green channels. GFP Intensity values were collected for all 100 time
      points to yield expression profiles. Variations in GFP expression profiles
      resulted from differences in factors such as promoter strength, presence of a
      silencing suppressor, or nature of the promoter. In addition to quantification of
      GFP intensity, the image series were also used to generate time-lapse animations
      using ImageReady. Time-lapse animations revealed that the clear majority of cells
      displayed a relatively rapid increase in GFP expression, followed by a slow
      decline. Some cells occasionally displayed a sudden loss of fluorescence, which
      may be associated with rapid cell death. Apparent transport of GFP across the
      membrane and cell wall to adjacent cells was also observed. Time lapse animations
      provided additional information that could not otherwise be obtained using GFP
      Intensity profiles or single time point image collections.

PMID- 22157951
TI  - Is your patient high on "bath salts"?

PMID- 22157952
TI  - Monitoring protein adsorption with solid-state nanopores.
AB  - Solid-state nanopores have been used to perform measurements at the single
      molecule level to examine the local structure and flexibility of nucleic acids,
      the unfolding of proteins, and binding affinity of different ligands. By coupling
      these nanopores to the resistive-pulse technique, such measurements can be done
      under a wide variety of conditions and without the need for labeling. In the
      resistive-pulse technique, an ionic salt solution is introduced on both sides of
      the nanopore. Therefore, ions are driven from one side of the chamber to the
      other by an applied transmembrane potential, resulting in a steady current. The
      partitioning of an analyte into the nanopore causes a well-defined deflection in
      this current, which can be analyzed to extract single-molecule information. Using
      this technique, the adsorption of single proteins to the nanopore walls can be
      monitored under a wide range of conditions. Protein adsorption is growing in
      importance, because as microfluidic devices shrink in size, the interaction of
      these systems with single proteins becomes a concern. This protocol describes a
      rapid assay for protein binding to nitride films, which can readily be extended
      to other thin films amenable to nanopore drilling, or to functionalized nitride
      surfaces. A variety of proteins may be explored under a wide range of solutions
      and denaturing conditions. Additionally, this protocol may be used to explore
      more basic problems using nanopore spectroscopy.

PMID- 22157953
TI  - Accuracy of respiratory rate monitoring by capnometry using the Capnomask(R) in
      extubated patients receiving supplemental oxygen after surgery.
AB  - BACKGROUND: Respiratory monitoring is standard after anaesthesia and surgery.
      Abnormal respiratory rate is a sensitive indicator of respiratory problems, even
      in patients receiving supplemental oxygen, but the best method for its continuous
      measurement in spontaneously breathing patients is unclear. This study compared
      respiratory rate assessment by capnometry using a new oxygen mask with a carbon
      dioxide sampling port (Capnomask((r))) and thoracic impedance pneumography with
      clinical measurement (used as a reference method) in extubated patients receiving
      supplemental oxygen. METHODS: Adult males admitted to the post-anaesthesia care
      unit after general anaesthesia were studied. Immediately after extubation, a
      Capnomask((r)) connected to a capnometer was positioned appropriately.
      Respiratory rate was measured by visual inspection of chest movement for 1 min,
      by capnometry, and thoracic impedance pneumography. One set of measurements was
      obtained for every patient receiving supplemental oxygen at different flow rates.
      RESULTS: Twenty men, mean (inter-quartile range) age 54 (23-66) yr and BMI 25 (21
      31) kg m(-2), were studied. Compared with visual inspection, the bias and limits
      of agreement were 0.0 (1.0 to -1.0) bpm for the Capnomask((r)) and -2.2 (2.0 to 
      6.5) bpm for the impedance pneumography. The accuracy of respiratory rate
      assessment using Capnomask((r)) was not influenced by the supplemental oxygen
      flow rate. CONCLUSIONS: In extubated patients, continuous assessment of
      respiratory rate with the Capnomask((r)) is more accurate than by thoracic
      impedance pneumography even when supplemental oxygen is delivered at a high flow
      rate.

PMID- 22157954
TI  - Novel pulsatile cerebrospinal fluid model to assess pressure manometry and fluid
      sampling through spinal needles of different gauge: support for the use of a 22 G
      spinal needle with a tapered 27 G pencil-point tip.
AB  - BACKGROUND: Parallel-walled spinal needles <= 22 G are routinely used for lumbar
      puncture, despite a reported >= 32% incidence of post-dural puncture headache. A
      tapered spinal needle (22 G shaft, 27 G tip) is in use in our institution. We
      hypothesized that despite the smaller dural puncture hole, this needle has
      similar cerebrospinal fluid (CSF) pressure equilibration times and CSF sampling
      times to a standard 22 G needle and assessed a range of spinal needles using an
      experimental pulsatile CSF reservoir. METHODS: The pulsatile CSF reservoir had an
      oscillating pressure varying between 25 and 15 cm H(2)O at a cycle frequency of
      80 s(-1). We tested seven parallel-walled spinal needles (18-27 G) and the
      tapered 22/27 G needle. CSF pressure was measured every 2 s by manometry. The
      time to collect 1 ml CSF samples was measured. Saline 0.9% and mannitol 20% were
      tested separately. One-way ANOVA with Bonferroni post-hoc test was used to
      compare 22G, 27G and 22/27G needles. RESULTS: The mean [standard deviation (sd)]
      CSF pressure equilibration time (saline) was 40.7 (6.4), 108.7 (6.1), and 51.3
      (4.6) s for the 22, 27, and 22/27 G needles (P< 0.0001 for comparisons between 27
      G and other needles). The mean (sd) CSF sampling time (saline) was 40.3 (3.1),
      225.3 (10.0), and 63.0 (5.2) s for the 22, 27, and 22/27 G needles (P< 0.0001 for
      comparisons between 27 G and other needles, and P= 0.019 between 22 and 22/27 G
      needles). Saline was different from mannitol for both measurements and all
      needles (P< 0.0001). CONCLUSIONS: A 22/27 G tapered spinal needle has similar
      flow properties to the 22 G needle, despite a 27 G tip.

PMID- 22157955
TI  - Single-molecule studies reveal the function of a third polymerase in the
      replisome.
AB  - The Escherichia coli replisome contains three polymerases, one more than
      necessary to duplicate the two parental strands. Using single-molecule studies,
      we reveal two advantages conferred by the third polymerase. First, dipolymerase
      replisomes are inefficient at synthesizing lagging strands, leaving single-strand
      gaps, whereas tripolymerase replisomes fill strands almost to completion. Second,
      tripolymerase replisomes are much more processive than dipolymerase replisomes.
      These features account for the unexpected three-polymerase-structure of bacterial
      replisomes.

PMID- 22157956
TI  - Intrinsic tethering activity of endosomal Rab proteins.
AB  - Rab small G proteins control membrane trafficking events required for many
      processes including secretion, lipid metabolism, antigen presentation and growth
      factor signaling. Rabs recruit effectors that mediate diverse functions including
      vesicle tethering and fusion. However, many mechanistic questions about Rab
      regulated vesicle tethering are unresolved. Using chemically defined reaction
      systems, we discovered that Vps21, a Saccharomyces cerevisiae ortholog of
      mammalian endosomal Rab5, functions in trans with itself and with at least two
      other endosomal Rabs to directly mediate GTP-dependent tethering. Vps21-mediated
      tethering was stringently and reversibly regulated by an upstream activator,
      Vps9, and an inhibitor, Gyp1, which were sufficient to drive dynamic cycles of
      tethering and detethering. These experiments reveal a previously undescribed mode
      of tethering by endocytic Rabs. In our working model, the intrinsic tethering
      capacity Vps21 operates in concert with conventional effectors and SNAREs to
      drive efficient docking and fusion.

PMID- 22157957
TI  - An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for
      atypical ubiquitin chains.
AB  - Eight different types of ubiquitin linkages are present in eukaryotic cells that
      regulate diverse biological processes. Proteins that mediate specific assembly
      and disassembly of atypical Lys6, Lys27, Lys29 and Lys33 linkages are mainly
      unknown. We here reveal how the human ovarian tumor (OTU) domain deubiquitinase
      (DUB) TRABID specifically hydrolyzes both Lys29- and Lys33-linked diubiquitin. A
      crystal structure of the extended catalytic domain reveals an unpredicted ankyrin
      repeat domain that precedes an A20-like catalytic core. NMR analysis identifies
      the ankyrin domain as a new ubiquitin-binding fold, which we have termed AnkUBD,
      and DUB assays in vitro and in vivo show that this domain is crucial for TRABID
      efficiency and linkage specificity. Our data are consistent with AnkUBD
      functioning as an enzymatic S1' ubiquitin-binding site, which orients a ubiquitin
      chain so that Lys29 and Lys33 linkages are cleaved preferentially.

PMID- 22157958
TI  - Fluorescent fusion protein knockout mediated by anti-GFP nanobody.
AB  - The use of genetic mutations to study protein functions in vivo is a central
      paradigm of modern biology. Recent advances in reverse genetics such as RNA
      interference and morpholinos are widely used to further apply this paradigm.
      Nevertheless, such systems act upstream of the proteic level, and protein
      depletion depends on the turnover rate of the existing target proteins. Here we
      present deGradFP, a genetically encoded method for direct and fast depletion of
      target green fluorescent protein (GFP) fusions in any eukaryotic genetic system.
      This method is universal because it relies on an evolutionarily highly conserved
      eukaryotic function, the ubiquitin pathway. It is traceable, because the GFP tag
      can be used to monitor the protein knockout. In many cases, it is a ready-to-use
      solution, as GFP protein-trap stock collections are being generated in Drosophila
      melanogaster and in Danio rerio.

PMID- 22157960
TI  - Predictive and prognostic factors for non-small cell lung cancer--potholes in the
      road to the promised land.

PMID- 22157959
TI  - Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of
      pluripotency factor Lin28.
AB  - Lin28 inhibits the biogenesis of let-7 miRNAs through a direct interaction with
      the terminal loop of pre-let-7. This interaction requires the zinc-knuckle
      domains of Lin28. We show that the zinc knuckle domains of Lin28 are sufficient
      to provide binding selectivity for pre-let-7 miRNAs and present the NMR structure
      of human Lin28 zinc knuckles bound to the short sequence 5'-AGGAGAU-3'. The
      structure reveals that each zinc knuckle recognizes an AG dinucleotide separated
      by a single nucleotide spacer. This defines a new 5'-NGNNG-3' consensus motif
      that explains how Lin28 selectively recognizes pre-let-7 family members. Binding
      assays in cell lysates and functional assays in cultured cells demonstrate that
      the interactions observed in the solution structure also occur between the full
      length protein and members of the pre-let-7 family. The consensus sequence
      explains several seemingly disparate previously published observations on the
      binding properties of Lin28.

PMID- 22157962
TI  - Cancer care during natural disasters.

PMID- 22157963
TI  - Can patient navigation help resolve gaps in cancer care?

PMID- 22157961
TI  - Prognostic and predictive value of a malignancy-risk gene signature in early
      stage non-small cell lung cancer.
AB  - BACKGROUND: The malignancy-risk gene signature is composed of numerous
      proliferative genes and has been applied to predict breast cancer risk. We
      hypothesized that the malignancy-risk gene signature has prognostic and
      predictive value for early-stage non-small cell lung cancer (NSCLC) patients.
      METHODS: The ability of the malignancy-risk gene signature to predict overall
      survival (OS) of early-stage NSCLC patients was tested using a large NSCLC
      microarray dataset from the Director's Challenge Consortium (n = 442) and two
      independent NSCLC microarray datasets (n = 117 and 133, for the GSE13213 and
      GSE14814 datasets, respectively). An overall malignancy-risk score was generated
      by principal component analysis to determine the prognostic and predictive value
      of the signature. An interaction model was used to investigate a statistically
      significant interaction between adjuvant chemotherapy (ACT) and the gene
      signature. All statistical tests were two-sided. RESULTS: The malignancy-risk
      gene signature was statistically significantly associated with OS (P < .001) of
      NSCLC patients. Validation with the two independent datasets demonstrated that
      the malignancy-risk score had prognostic and predictive values: Of patients who
      did not receive ACT, those with a low malignancy-risk score had increased OS
      compared with a high malignancy-risk score (P = .007 and .01 for the GSE13212 and
      GSE14814 datasets, respectively), indicating a prognostic value; and in the
      GSE14814 dataset, patients receiving ACT survived longer in the high malignancy
      risk score group (P = .03), and a statistically significant interaction between
      ACT and the signature was observed (P = .02). CONCLUSIONS: The malignancy-risk
      gene signature was associated with OS and was a prognostic and predictive
      indicator. The malignancy-risk gene signature could be useful to improve
      prediction of OS and to identify those NSCLC patients who will benefit from ACT.

PMID- 22157964
TI  - Spicy approach to cancer treatment.

PMID- 22157965
TI  - Developing nations face challenges as breast cancer rises.

PMID- 22157966
TI  - StatBite: Estimated female breast cancer incidence by age in less developed
      regions.

PMID- 22157969
TI  - Tissue Doppler time intervals and derived indices in hypoplastic left heart
      syndrome.
AB  - AIMS: To describe tissue Doppler time intervals and derived indices in
      hypoplastic left heart syndrome (HLHS) across surgical stages, taking account of
      age-related changes in the heart rate. Correlation of the myocardial performance
      index (MPI) and the systolic to diastolic (S:D) time ratio with other
      echocardiographic and magnetic resonance imaging (MRI) measures of cardiac
      performance. METHODS AND RESULTS: Fifty-seven patients at different stages of
      HLHS palliation were studied prospectively using tissue Doppler imaging of the
      right ventricular free wall, with simultaneous cardiac MRI in the majority. Both
      isovolumic contraction time and isovolumic relaxation time were prolonged
      compared with the normal left and right ventricle: median (range) z-scores for
      the tricuspid annulus 1.9 (-1.2 to 9.3) and 1.3 (-2.0 to 5.5), respectively. When
      adjusted for heart rate, the ejection, systolic, and diastolic times in HLHS were
      not significantly different from published normal data. The MPI was increased at
      all surgical stages in HLHS. Neither MPI nor heart rate-specific S:D time ratio z
      score correlated with MRI ejection fraction or indexed cardiac output when the
      confounding effect of significant tricuspid regurgitation was taken into
      consideration. CONCLUSION: The prolongation in isovolumic relaxation and
      contraction times may be due to adaptation or reduced myocardial performance.
      Differences in the S:D time ratio between surgical stages can be accounted for by
      the heart rate alone. Neither MPI z-score nor S:D z-score correlated with MRI or
      other echocardiographic indices of systolic or diastolic function with the
      exception of a negative correlation between central venous pressure and S:D ratio
      z-score.

PMID- 22157970
TI  - The evolution of a statewide network: the Bay Area Simulation Collaborative.
AB  - The Bay Area Simulation Collaborative (BASC), established in 2007, is a group of
      more than 100 schools of nursing and hospitals, totaling more than 600 faculty
      and hospital educators, from both service and academia in the ten counties that
      comprise the San Francisco Bay Area. The California Institute for Nursing &
      Health Care leads the BASC, which was funded through a grant from the Gordon and
      Betty Moore Foundation. This 3-year project was designed to train and educate
      nursing faculty and hospital educators in the concepts of simulation. It was also
      designed to develop clinical simulation scenarios for use within the BASC.
      Finally, the project implemented a research and evaluation agenda to demonstrate
      that simulation makes a positive difference in the critical thinking skills of
      nursing students. This article will describe the evolution, purpose, and goals of
      the BASC and how the initial investment has been leveraged to create addition
      regional collaboratives in the state and ultimately, the California Simulation
      Alliance.

PMID- 22157971
TI  - SILEC: a protocol for generating and using isotopically labeled coenzyme A mass
      spectrometry standards.
AB  - Stable isotope labeling by essential nutrients in cell culture (SILEC) was
      recently developed to generate isotopically labeled coenzyme A (CoA) and short
      chain acyl-CoA thioesters. This was accomplished by modifying the widely used
      technique of stable isotope labeling by amino acids in cell culture to include
      [(13)C(3)(15)N]-pantothenate (vitamin B(5)), a CoA precursor, instead of the
      isotopically labeled amino acids. The lack of a de novo pantothenate synthesis
      pathway allowed for efficient and near-complete labeling of the measured CoA
      species. This protocol provides a step-by-step approach for generating stable
      isotope-labeled short-chain acyl-CoA internal standards in mammalian and insect
      cells as well as instructions on how to use them in stable isotope dilution mass
      spectrometric-based analyses. Troubleshooting guidelines, as well as a list of
      unlabeled and labeled CoA species, are also included. This protocol represents a
      prototype for generating stable isotope internal standards from labeled essential
      nutrients such as pantothenate. The generation and use of SILEC standards takes
      approximately 2-3 weeks.

PMID- 22157972
TI  - Construction of implantable optical fibers for long-term optogenetic manipulation
      of neural circuits.
AB  - In vivo optogenetic strategies have redefined our ability to assay how neural
      circuits govern behavior. Although acutely implanted optical fibers have
      previously been used in such studies, long-term control over neuronal activity
      has been largely unachievable. Here we describe a method to construct implantable
      optical fibers to readily manipulate neural circuit elements with minimal tissue
      damage or change in light output over time (weeks to months). Implanted optical
      fibers readily interface with in vivo electrophysiological arrays or
      electrochemical detection electrodes. The procedure described here, from implant
      construction to the start of behavioral experimentation, can be completed in
      approximately 2-6 weeks. Successful use of implantable optical fibers will allow
      for long-term control of mammalian neural circuits in vivo, which is integral to
      the study of the neurobiology of behavior.

PMID- 22157973
TI  - Quantitative imaging of membrane lipid order in cells and organisms.
AB  - It is now recognized that lipids and proteins in cellular membranes are not
      homogenously distributed. A high degree of membrane order is the biophysical
      hallmark of cholesterol-enriched lipid rafts, which may induce the lateral
      sorting of proteins within the membrane. Here we describe a quantitative
      fluorescence microscopy technique for imaging localized lipid environments and
      measuring membrane lipid order in live and fixed cells, as well as in intact
      tissues. The method is based on the spectral ratiometric imaging of the polarity
      sensitive membrane dyes Laurdan and di-4-ANEPPDHQ. Laurdan typically requires
      multiphoton excitation, making it suitable for the imaging of tissues such as
      whole, living zebrafish embryos, whereas di-4-ANEPPDHQ imaging can be achieved
      with standard confocal microscopes. This approach, which takes around 4 h,
      directly examines the organization of cellular membranes and is distinct from
      alternative approaches that infer membrane order by measuring probe partitioning
      or dynamics.

PMID- 22157974
TI  - Depletion of hemoglobin and carbonic anhydrase from erythrocyte cytosolic samples
      by preparative clear native electrophoresis.
AB  - Proteomic analysis of red cells is compromised by the presence of high-abundance
      proteins (hemoglobin and carbonic anhydrase-1), which completely obscure low
      abundance species. The depletion method presented here involves performing native
      gel electrophoresis in a polyacrylamide gel tube using a modified electroelution
      cell. The electrophoretic run is interrupted intermittently to allow the recovery
      of at least three different liquid fractions, which can be analyzed by both
      native PAGE and 2D isoelectric focusing SDS-PAGE, or by shotgun mass spectrometry
      analysis after trypsin in-solution protein digestion. This low-cost, reproducible
      technique can be used to process large amounts of sample, and it increases the
      likelihood of detecting low-abundance proteins, thereby resulting in greater
      proteome coverage. The separation procedure takes approximately 6-7 h.

PMID- 22157975
TI  - Isolation of retinal stem cells from the mouse eye.
AB  - The adult mouse retinal stem cell (RSC) is a rare quiescent cell found within the
      ciliary epithelium (CE) of the mammalian eye(1,2,3). The CE is made up of non
      pigmented inner and pigmented outer cell layers, and the clonal RSC colonies that
      arise from a single pigmented cell from the CE are made up of both pigmented and
      non-pigmented cells which can be differentiated to form all the cell types of the
      neural retina and the RPE.  There is some controversy about whether all the cells
      within the spheres all contain at least some pigment(4); however the cells are
      still capable of forming the different cell types found within the neural
      retina(1-3). In some species, such as amphibians and fish, their eyes are capable
      of regeneration after injury(5), however; the mammalian eye shows no such
      regenerative properties.  We seek to identify the stem cell in vivo and to
      understand the mechanisms that keep the mammalian retinal stem cells quiescent(6
      8), even after injury as well as using them as a potential source of cells to
      help repair physical or genetic models of eye injury through transplantation(9
      12).  Here we describe how to isolate the ciliary epithelial cells from the mouse
      eye and grow them in culture in order to form the clonal retinal stem cell
      spheres.  Since there are no known markers of the stem cell in vivo, these
      spheres are the only known way to prospectively identify the stem cell population
      within the ciliary epithelium of the eye.

PMID- 22157976
TI  - OCT for assessing artificial tears effectiveness in contact lens wearers.
AB  - PURPOSE: To apply a commercially available high-resolution spectral domain
      optical coherence tomographer (SOCT) to assess the change in tear volume after
      application of a new artificial tears formulation specifically developed for
      contact lens (CL) users. METHODS: Twenty OD from young healthy CL wearers (mean
      age, 24.7 +/- 3.5 years) with refractive errors ranging from -0.75 to -2.50 D
      (mean, -1.56 +/- 0.69 D) were examined. All subjects were fitted with Focus
      Dailies CL (Ciba Vision), and two drops of Blink Contacts (AMO), lubricating
      formulation specifically developed for CL wearers, were instilled after baseline
      measures. Tear meniscus volume (TMV) was measured immediately after and 1 min,
      10, 30, and 60 min after instillation using the Copernicus HR SOCT (Optopol
      Tech., SA, Poland). TMV was calculated from the local area from tomograms
      assuming a regular distribution of the tear meniscus across the eyelid. Three
      scans were taken at each of the time points. RESULTS: Mean meniscus volume
      without CL was 1.35 +/- 1.18 MUL, volume with CL was higher, 1.71 +/- 1.56 MUL
      but not significantly different (mean difference, 0.36 +/- 1.31 MUL). After
      instillation of Blink Contacts eye drops, meniscus volume increased to an average
      of 4.10 +/- 2.91 MUL. Repeated measures analysis of variance showed that values
      after 10 min were significantly higher than before instillation of eye drops (p <
      0.01; mean difference, 0.77 +/- 0.65 MUL). After 30 and 60 minutes, values of TMV
      decreased to almost baseline (average mean difference from baseline 0.19 +/- 0.18
      MUL at t30, p < 0.001, and 0.06 +/- 0.08 MUL at t60, p = 0.004). CONCLUSIONS:
      High-resolution imaging of the lower tear film meniscus with SOCT systems
      provides useful measures of tear volume. An artificial tear formulation provides
      a change in tear volume that is maintained beyond 10 min, although further study,
      using control groups, would be desirable to determine the consistency of those
      higher-than-baseline values observed over time.

PMID- 22157977
TI  - IOL with square-edged optic and reduced dysphotopsia.
AB  - PURPOSE: To demonstrate a new optic edge design that preserves advantages of the
      square-edged optic and substantially reduces intensity of the light pattern
      formed at the retina by internal reflection off the optic edge. METHODS: Non
      sequential ray tracing (Zemax optical design software) was used to model light
      intensity and distribution of the light pattern at the retina formed by internal
      light reflection off different optic edges in intraocular lens of otherwise
      equivalent configurations. RESULTS: A maximum intensity of the light pattern
      formed by internal reflection off the optic edge occurs within 35 to 42.5 degrees
      of the field angle. An undulated square-edged optic reduces the maximum light
      intensity of the light pattern formed at the retina by a factor of 5, when
      compared with a conventional double square-edged optic. CONCLUSIONS: Edge
      undulation of the square-edged optic is an effective addition to intraocular lens
      designs that reduces the potential for dysphotopsia caused by the optic edge
      internal reflection of light.

PMID- 22157978
TI  - Design and validation of a method for evaluation of interocular interaction.
AB  - PURPOSE: To design a simple viewing system allowing dichoptic masking, and to
      validate this system in adults and children with normal vision. METHODS: A Trial
      Frame Apparatus (TFA) was designed to evaluate interocular interaction. This
      device consists of a trial frame, a 1 mm pinhole in front of the tested eye and a
      full or partial occluder in front of the non-tested eye. The difference in visual
      function in one eye between the full- and partial-occlusion conditions was termed
      the Interaction Index. In experiment 1, low-contrast acuity was measured in six
      adults using five types of partial occluder. Interaction Index was compared
      between these five, and the occluder showing the highest Index was used in
      experiment 2. In experiment 2, low-contrast acuity, contrast sensitivity, and
      alignment sensitivity were measured in the non-dominant eye of 45 subjects (15
      older adults, 15 young adults, and 15 children), using the TFA and an existing
      well-validated device (shutter goggles) with full and partial occlusion of the
      dominant eye. These measurements were repeated on 11 subjects of each group using
      TFA in the partial-occlusion condition only. Repeatability of visual function
      measurements using TFA was assessed using the Bland-Altman method and agreement
      between TFA and goggles in terms of visual functions and interactions was
      assessed using the Bland-Altman method and t-test. RESULTS: In all three subject
      groups, the TFA showed a high level of repeatability in all visual function
      measurements. Contrast sensitivity was significantly poorer when measured using
      TFA than using goggles (p < 0.05). However, Interaction Index of all three visual
      functions showed acceptable agreement between TFA and goggles (p > 0.05).
      CONCLUSIONS: The TFA may provide an acceptable method for the study of some forms
      of dichoptic masking in populations where more complex devices (e.g., shutter
      goggles) cannot be used.

PMID- 22157979
TI  - Modeling the prevalence of age-related cataract: Waterloo eye study.
AB  - PURPOSE: To report on the prevalence of age-related (AR) cataract in an
      optometric clinic population including male and female subgroups. METHODS:
      Retrospective patient file data reviewed for the Waterloo Eye Study database
      included age, sex, date of lens extraction (LE), and presence of AR cataract
      [nuclear sclerosis (NS), cortical cataracts (CC), posterior subcapsular (PSC) or
      associated LE]. Prevalence (%) was calculated for overall AR cataract, NS, CC,
      PSC, and bilateral LE for all Waterloo Eye Study patients. Logistic regression
      analysis was used to create age functions for overall AR prevalence and for
      significant differences in cataract types for males and females. The distribution
      of homogeneous and mixed cataract and mean age of first LE were determined for
      males and females. RESULTS: The prevalence of all AR, NS, CC, PSC, and bilateral
      LE was 35.3, 28.8, 9.9, 3.6, and 14.0%, respectively. Being female was associated
      with an increased prevalence of CC (odds ratio = 1.54, 95% confidence interval,
      1.27 to 1.88) and bilateral LE (odds ratio = 1.41, 95% confidence interval, 1.09
      to 1.84). Females reached 50% prevalence earlier than men for CC (76.7 vs. 82.6
      years, p 0.05) and bilateral LE (84.6 vs. 90.5 years, p 0.05). Males had an
      earlier age of first LE than females (70.4 vs. 73.2 years; p 0.01). CONCLUSIONS:
      Logistic regression modeling indicates that being female in this optometric
      clinic population was associated with an increased prevalence of CC, mixed
      cataract, surgical intervention, and later age of first LE. These data are
      important for public health planning.

PMID- 22157980
TI  - Ocular examination for diagnosis of end stage pulmonary sarcoidosis.
AB  - PURPOSE: Pulmonary sarcoidosis without overt radiographic fibrosis may be
      difficult to diagnose; ophthalmic examination aided diagnosis of our case. CASE
      REPORT: The patient was a 55-year-old man whose dyspnea had been misdiagnosed and
      who had been treated for chronic obstructive pulmonary disease. Physical and
      ophthalmic examinations including slitlamp, fundoscopic, and fluorescein
      angiography examinations were administered. CONCLUSIONS: Patient's ophthalmic
      findings suggested ocular sarcoidosis, leading to confirmation of his pulmonary
      sarcoidosis by histopathological examination of lung biopsy samples. Careful,
      knowledgeable ophthalmic examination can help in diagnosing systemic sarcoidosis.

PMID- 22157981
TI  - Influence of paradoxical sleep deprivation and sleep recovery on testosterone
      level in rats of different ages.
AB  - This study was performed to assess serum testosterone alterations induced by
      paradoxical sleep deprivation (PSD) and to verify their attenuation during sleep
      recovery (SR) based on different durations and ages. Wistar male rats aged 12
      weeks for the younger group and 20 weeks for the elder group were randomly
      distributed into one of the following groups: a control group (cage and
      platform), 3-day SD, 5-day SD, 7-day SD, 1-day SR, 3-day SR and 5-day SR groups.
      For PSD, the modified multiple platform method was used to specifically limit
      rapid eye movement (REM) sleep. Differences in the testosterone and luteinizing
      hormone levels between the younger group and the elder group according to
      duration of PSD and SR recovery were analysed. Testosterone continued to fall
      during the sleep deprivation period in a time-dependent manner in both the
      younger (P=0.001, correlation coefficient r=-0.651) and elder groups (P=0.001,
      correlation coefficient r=-0.840). The elder group showed a significantly lower
      level of testosterone compared with the younger group after PSD. Upon SR after 3
      days of PSD, the testosterone level continued to rise for 5 days after sleep
      recovery in the younger group (P=0.013), whereas testosterone concentrations
      failed to recover until day 5 in the elder group. PSD caused a more detrimental
      effect on serum testosterone in the elder group compared to the younger group
      with respect to decreases in luteinizing hormone (LH) levels. The replenishment
      of serum testosterone level was prohibited in the elder group suggesting that the
      effects of SD/SR may be age-dependent. The mechanism by which SD affects serum
      testosterone and how age may modify the process are still unclear.

PMID- 22157983
TI  - Influence of immune inflammation on androgen receptor expression in benign
      prostatic hyperplasia tissue.
AB  - This study was designed to investigate the association between immune
      inflammation and androgen receptor (AR) expression in benign prostatic
      hyperplasia (BPH). We retrospectively analyzed 105 prostatectomy specimens. An
      immune inflammation score for each specimen was defined by combining three
      immunohistochemical markers (CD4, CD8 and CD20). The immunohistochemical markers
      were CD4 and CD8 for T lymphocytes, CD20 for B lymphocytes and AR antibody for
      the AR in BPH samples. Rates of CD4, CD8, CD20 and AR expression in BPH were 20
      (19.0%), 21 (20.0%), 101 (96.2%) and 48 (45.7%), respectively. Total prostate
      volume (TPV) was higher in the immune inflammation group than in the non-immune
      inflammation group (62.7 ml vs. 49.2 ml, t=2.482, P<0.05). Patients in the immune
      inflammation group had a higher serum prostate-specific antigen (PSA) than those
      in the non-inflammation group (7.5 ng ml(-1 )vs. 5.4 ng ml(-1), t=2.771, P<0.05).
      Specifically, the immune inflammation group showed a higher rate of AR expression
      than the non-inflammation group (56.1% vs. 28.2%, chi(2)=7.665, P<0.05). Our
      study revealed a strong association between immune inflammation and TPV, serum
      PSA and AR expression in BPH tissue. Prostate hyperplasia caused by an immune
      inflammatory process may contribute to BPH progression over time. Therefore, the
      inflammatory response involved in BPH may be a prime therapeutic target.

PMID- 22157984
TI  - Is there a correlation between the outcome of transurethral resection of prostate
      and preoperative degree of bladder outlet obstruction?
AB  - To compare the impact of transurethral resection of prostate (TURP) on symptom
      scores and maximal flow rates (Qmax) in patients with equivocal bladder outlet
      obstruction (BOO) and definite BOO and to assess the relationship between the
      surgical outcomes and degree of preoperative BOO, we prospectively evaluated men
      with lower urinary tract symptoms and bladder outlet obstruction index (BOOI)
      greater than 20, who were refractory to conventional medical treatment and
      underwent TURP. Urodynamic evaluation, International Prostate Symptom Score
      (IPSS), uroflowmetry, post-void residual volume (PVR) check and transrectal
      ultrasound were performed. 20<BOOI<40 was defined as equivocal BOO and BOOI>=40
      as definite BOO. Changes of IPSS, Qmax, PVR and correlation analysis was
      performed between the degree of improvement of Qmax, subdomains of IPSS and BOOI.
      Fifty-four patients showed equivocal BOO and 80 patients showed definite BOO.
      Preoperatively equivocal BOO group and definite BOO group showed significant
      differences in maximal bladder capacity and prevalence of detrusor overactivity,
      whereas no difference was noted in prostate volume. Postoperatively both groups
      showed improvements in Qmax, obstructive (IPSSO) and irritative (IPSSI) subdomain
      of IPSS, but the degree of improvement in Qmax and IPSSI subdomain was
      statistically significantly greater in definite BOO group. The degree of
      improvement of Qmax and IPSSI showed weak correlation with preoperative BOOI. As
      a weak correlation was identified between preoperative degree of BOO and outcome
      of TURP, other factors other than BOOI such as severity of patients' symptoms
      should be considered in deciding treatment modality.

PMID- 22157982
TI  - Advanced paternal age and reproductive outcome.
AB  - Women have been increasingly delaying the start of motherhood in recent decades.
      The same trend is seen also for men. The influence of maternal age on fertility,
      chromosomal anomalies, pregnancy complications, and impaired perinatal and post
      natal outcome of offspring, has been thoroughly investigated, and these aspects
      are clinically applied during fertility and pregestational counseling. Male aging
      and reproductive outcome has gained relatively less attention. The purpose of
      this review is to evaluate updated and relevant literature on the effect of
      paternal age on reproductive outcome.

PMID- 22157985
TI  - Testicular biopsy: clinical practice and interpretation.
AB  - Testicular biopsy was considered the cornerstone of male infertility diagnosis
      for many years in men with unexplained infertility and azoospermia. Recent
      guidelines for male infertility have limited the indications for a diagnostic
      testicular biopsy to the confirmation of obstructive azoospermia in men with
      normal size testes and normal reproductive hormones. Nowadays, testicular
      biopsies are mainly performed for sperm harvesting in men with non-obstructive
      azoospermia, to be used for intracytoplasmic sperm injection. Testicular biopsy
      is also performed in men with risk factors for testicular malignancy. In a
      subgroup of infertile men, there is an increased risk for carcinoma in situ of
      the testis, especially in men with a history of cryptorchidism and testicular
      malignancy and in men with testicular atrophy. Ultrasonographic abnormalities,
      such as testicular microlithiasis, inhomogeneous parenchyma and lesions of the
      testes, further increase the risk of carcinoma in situ (CIS) in these men. For an
      accurate histological classification, proper tissue handling, fixation,
      preparation of the specimen and evaluation are needed. A standardized approach to
      testicular biopsy is recommended. In addition, approaches to the detection of CIS
      of the testis testicular immunohistochemistry are mandatory. In this mini-review,
      we describe the current indications for testicular biopsies in the diagnosis and
      management of male infertility.

PMID- 22157986
TI  - Outcomes for offspring of men having ICSI for male factor infertility.
AB  - Since the introduction of intracytoplasmic sperm injection (ICSI) using single
      sperm isolated from testicular tissue in men with obstructive and non-obstructive
      azoospermia, or using ejaculated sperm in those with poor semen quality, there
      have been concerns that this might have adverse effects on the offspring compared
      to conventional in vitro fertilisation (IVF) and natural conceptions. ICSI is
      done for reasons other than male factor infertility, and on the whole has not
      been shown to have any more negative effects than those seen with IVF. There have
      however, been very few studies of ICSI with a focus on, or large enough numbers
      to examine, the specific outcomes associated with male factor infertility. From
      the limited information available in relation to the source of the sperm and
      aetiology of infertility in the presence of ICSI, there appears to be no
      increased risk of congenital malformations. There is, however, a small increase
      in both de novo and inherited chromosome abnormalities. In terms of growth and
      neurodevelopment, there are very few studies, and so far, no adverse outcomes
      have been found in young children whose fathers have a sperm defect. The origin
      of the sperm used in ICSI does not have a major influence on the early life
      outcomes for the offspring, but transgenerational and epigenetic effects remain
      unknown. When the male factor infertility is known or thought to be due to a Y
      chromosome deletion, this information should be given to the young male offspring
      at a time that will ensure his own reproductive health and plans are optimized.

PMID- 22157988
TI  - Setting the standard for nursing education.
AB  - This column provides information on accreditation for nursing programs of all
      types. Readers may submit questions to the National League for Nursing
      Accrediting Commission. General questions of interest to a wide audience will be
      addressed in this column, whereas more specific questions or those requiring
      confidentiality will be answered directly.

PMID- 22157987
TI  - Lessons learned from an osteoporosis clinical trial in frail long-term care
      residents.
AB  - BACKGROUND: Although osteoporosis affects women of all ages, the impact is most
      pronounced in frail residents in long-term care. Nevertheless, few interventional
      trials have been performed in this population, and few data on therapeutic
      alternatives are available in this cohort. PURPOSE: We describe the challenges
      and lessons learned in developing and carrying out a trial in frail long-term
      care residents. METHODS: The Zoledronic acid in frail Elders to STrengthen bone
      (ZEST) study was designed to examine the safety and efficacy of a single-dose
      therapy for osteoporosis in frail residents in long-term care in the Pittsburgh
      area. Women with osteoporosis who were 65 years of age and older and currently
      not on therapy were randomized in a blinded fashion to intravenous zoledronic
      acid or placebo. Follow-up of each participant was planned for 2 years. All
      participants received appropriate calcium and vitamin D supplementation. RESULTS:
      Seven hundred and thirty-three contacts were made with long-term care residents
      of nine participating facilities. Of 252 women screened, 181 were eligible,
      enrolled, and randomized. Multiple barriers to research in long-term-care
      facilities were encountered but overcome with direct communication, information
      sessions, in-service trainings, and social events. Lessons learned included
      designing the study in a manner that avoided placing an additional burden on an
      already overcommitted facility staff, a two-stage consent process to separate
      screening from randomization, and a flexible examination schedule to accommodate
      residents while obtaining the necessary outcome measurements. Furthermore, a
      mobile unit accessible to participants containing state-of-the-art dual x-ray
      absorptiometry (DXA), assessment for vertebral fractures, and phlebotomy
      equipment allows all assessments to be performed on-site at each facility.
      Serious adverse events are collected from affiliated hospitals in real time with
      a novel electronic surveillance system. LIMITATIONS: The major limitation is
      selection of outcomes that can be assessed at participating facilities and do not
      require transport of participants to hospitals or clinics. CONCLUSIONS: Clinical
      research for osteoporosis can be successfully and safely performed with frail
      residents in long-term care facilities. Lessons learned from this study may
      inform future investigations among frail elderly residents of these facilities.

PMID- 22157990
TI  - Cloud computing.
AB  - In this bimonthly series, the author examines how nurse educators can use
      Internet and Web-based technologies such as search, communication, and
      collaborative writing tools; social networking and social bookmarking sites;
      virtual worlds; and Web-based teaching and learning programs. This article
      describes how cloud computing can be used in nursing education.

PMID- 22157991
TI  - Creating an effective dean's board.
AB  - Many new nursing leaders assuming deanships, assistant deanships, or interim
      deanships have limited education, experience, or background to prepare them for
      the job. To assist new deans and those aspiring to be deans, Jana L. Pressler,
      PhD, RN, and Carole A. Kenner, PhD, RNC-NIC, FAAN, the editors of this
      department, address common issues, challenges, and opportunities that face
      academic executive teams, such as negotiating an executive contract; obtaining
      faculty lines; building effective work teams; managing difficult employees; and
      creating nimble organizational structure to respond to changing consumer,
      healthcare delivery, and community needs. In this article, the editors asked
      guest author, Dr Judy Wright Lott, to discuss the important role advisory boards
      have for deans.

PMID- 22157993
TI  - Nursing students as joint commission surveyors.

PMID- 22157994
TI  - Conducting nursing research with undergraduate students: a collaborative,
      participatory approach.

PMID- 22157995
TI  - Plagiarism: using a collaborative approach in an online allied health professions
      course.
AB  - The purpose of the study was to evaluate the effectiveness of interventions to
      increase the awareness and understanding of plagiarism among undergraduate
      students enrolled in an online allied health professions course in a community
      college in the Midwestern United States. The results suggested that the
      interventions were effective in educating students about how to avoid plagiarism.

PMID- 22157997
TI  - Pairing students in clinical assignments to develop collaboration and
      communication skills.
AB  - Skillful collaboration and communication among healthcare team members are
      associated with favorable patient outcomes. Student nurses need opportunities for
      supervised development of these crucial and intertwined skills. The author
      describes the implementation of a practice-change project for simultaneously
      developing collaboration and communication skills by pairing prelicensure student
      nurses in clinical assignments. This easily adapted strategy increases options
      for faculty looking to stimulate student acquisition of these professional
      skills.

PMID- 22157999
TI  - Integration of chronic illness care into a primary healthcare focused nursing
      curriculum.
AB  - Staggering statistics highlight the impact of chronic illness globally on the
      health of individuals and communities and in the global arena. Despite nursing's
      potential role to ameliorate this situation, nursing curricula is traditionally
      weak in this area. This article highlights one nursing program's third year
      baccalaureate chronic illness courses that were developed within a primary
      healthcare framework.

PMID- 22158000
TI  - Are nursing faculty ready to integrate genomic content into curricula?
AB  - Genomics is an emerging field with newly developed expectations for all
      healthcare professionals. Nursing faculty are critical to preparing the future
      nursing workforce in genomics but faculty knowledge, receptivity, and interest in
      learning more about this subject were unknown. The authors discuss the process
      used to assess nursing faculty's readiness to change as a way to substantiate the
      need for faculty training.

PMID- 22158002
TI  - Preparing BSN students for the doctor of nursing practice (DNP) application
      process: the faculty role.
AB  - With the recent development of BSN-to-DNP programs, many BSN students and
      graduates are making applications. However, few BSN programs instruct students on
      how to successfully apply to doctoral programs. The author provides
      recommendations for BSN faculty on how to prepare BSN students for the
      application process to doctoral programs.

PMID- 22158003
TI  - An example of a statistics course in a doctor of nursing practice (DNP) program.
AB  - The current healthcare environment requires RNs and advanced practice nurses
      (APNs) to be proficient in critique and utilization of healthcare research to
      inform an evidence base for practice. Many practicing RNs and APNs lack
      competency in statistical analysis and interpretation, and knowledge in the
      conduct of nursing research. Doctor of Nursing Practice (DNP) students need this
      knowledge to address researchable problems found in their own practice
      environments and, as leaders in practice, to mentor colleagues and other members
      of the healthcare team. The authors describe a DNP statistics course including
      its design and composition and demonstrate how using traditional, data-oriented,
      and student project approaches yields positive learning outcomes.

PMID- 22158004
TI  - BMI, waist circumference, and selected cardiovascular disease risk factors among
      preschool-age children.
AB  - In adults, overweight is often associated with other cardiovascular disease (CVD)
      risk factors. We determined whether these associations were also present in young
      children. This study examined the relationships between elevated BMI (>=85th and
      >=95th percentiles for age and sex) and the highest quintile of waist
      circumference (WC) with CVD risk factors, including fasting triglyceride (TGL),
      high- and low-density lipoprotein (HDL and LDL), total cholesterol (TC), non-HDL
      cholesterol, and C-reactive protein (CRP) in 3,644 3- to 6-year-old children
      included in the 1999-2008 National Health and Nutrition Examination Surveys
      (NHANES). Results showed that 20% (highest quintile) of the sample had a TC >170
      mg/dl, LDL >109 mg/dl, TGL >103 mg/dl, non-HDL >128 mg/dl, CRP >0.13 mg/dl, WC
      >57.2 cm, and HDL <42 mg/dl. Increased BMI and WC were associated with increased
      CRP levels in non-Hispanic black boys and girls, Hispanic boys, and non-Hispanic
      white girls, whereas elevated TGL and non-HDL cholesterol and low HDL cholesterol
      were generally associated with elevated BMI and WC in Hispanic children. TC and
      LDL cholesterol were not significantly associated with elevated weight in 3- to 6
      year-olds. BMI and WC were similar in predicting the same risk factors. In
      summary, this analysis shows that in preschool-age children, greater BMI and WC
      are associated with biomarkers that are related to CVD risk, but these
      associations vary by ethnicity. Child health providers should consider using both
      BMI and WC to identify young children who may be at risk for elevated CVD
      biomarkers.

PMID- 22158005
TI  - Similarity of the CDC and WHO weight-for-length growth charts in predicting risk
      of obesity at age 5 years.
AB  - The World Health Organization (WHO) 2006 weight-for-length (WFL) or BMI growth
      charts are now recommended as the new standard for children under 24 months. The
      objective of this study was to examine associations of ever being overweight
      during 1-24 months, based on the older Centers for Disease Control and Prevention
      (CDC) and WHO cutpoints, with risk of obesity at age 5 years. From well-child
      visits to a Massachusetts multi-site group practice during 1980-2008, we studied
      15,488 children with length/height and weight measurements at 1, 6, 12, 18, and
      24 months, and at 5 years. The main exposures were ever being overweight during 1
      24 months using each of three cutpoints: CDC WFL >= 95th percentile, WHO WFL or
      BMI >= 97.7th percentile. The main outcome was obesity at 5 years (CDC BMI >=
      95th percentile). We calculated multivariable odds ratios (ORs), adjusted for
      age, sex, race/ethnicity, and year. At 5 years, 10.8% of participants were obese.
      During 1-24 months, 21.3, 18.3, and 20.2% were ever overweight using CDC WFL, WHO
      WFL, and WHO BMI cutpoints, respectively. ORs (95% confidence interval (CI)) for
      associations of ever being overweight during 1-24 months with obesity at 5 years
      were 6.0 (5.4, 6.6), 6.3 (5.7, 7.0), and 6.0 (5.4, 6.7), respectively. Ever being
      overweight in the first 2 years of life is a strong predictor of obesity at 5
      years. CDC WFL, WHO WFL, and WHO BMI cutpoints for overweight in early childhood
      provided similar estimates of later obesity risk.

PMID- 22158006
TI  - Functional capacity of neutrophils from class III obese patients.
AB  - Class III obesity is associated with chronic inflammation and a variety of
      changes in immune function. Yet surprisingly little was known about the status of
      neutrophils that represent the first line of immune defense. The aim of this
      study was to assess key functions of neutrophils from class III obese patients,
      namely phagocytosis, superoxide production, chemotaxis, and response to endotoxin
      challenge, and compare their responses with lean controls. Thirty obese patients
      (BMI 48.8 +/- 6.6 kg/m(2)) with comorbidities such as diabetes, hyperlipidemia,
      high blood pressure, etc. and nine lean (BMI between 20 and 25) subjects were
      enrolled in the study. Neutrophils from class III obese patients phagocytosed
      Escherichia coli (E. coli) at similar rates and with adequate numbers of bacteria
      taken up per cell compared with cells from lean subjects. Neutrophil production
      of superoxide, which is key to rapid killing of pathogens, showed modest
      diminution in the class III obese, which increased among patients with BMI >50.
      Chemotactic activity of neutrophils from class III obese patients was not
      altered. However, neutrophils from obese subjects showed an increased response to
      low-dose endotoxin, with concomitant reduced apoptosis and extension of their
      half-life compared with lean subjects, which suggests possible
      hyperresponsiveness of these neutrophils. Overall, neutrophil activity was not
      significantly altered by age, gender, diabetic status, or hyperlipidemia.
      Collectively, these results suggest that class III obese patients, even with
      comorbidities, have normal or nearly normal phagocytic, chemotactic, and
      superoxide generating capacity.

PMID- 22158007
TI  - Early gestational gene transfer with targeted ATP7B expression in the liver
      improves phenotype in a murine model of Wilson's disease.
AB  - The ideal gene therapy for metabolical liver disorders would target hepatocytes
      before the onset of disease and be durable, non-toxic and non-immunogenic. Early
      gestational gene transfer can achieve such goals. Here, we demonstrate that
      prenatal gene transfer of human Atp7b reduces liver pathology and improves
      biochemical markers in Atp7b(-/-) mice, a murine model of Wilson's disease (WD).
      Following prenatal injection of lentivirus vector containing the human Atp7b gene
      under the transcriptional control of a liver-specific promoter, the full-length
      ATP7B was detectable in mouse livers for the entire duration of experiments (20
      weeks after birth). In contrast to a marked pathology in non-injected animals,
      livers from age-matched treated mice consistently demonstrated normal gross and
      histological morphology. Hepatic copper content was decreased in the majority of
      treated mice, although remaining copper levels varied. Improvement of hepatic
      copper metabolism was further apparent from the presence of copper-bound
      ceruloplasmin in the sera and normalization of the mRNA levels for HMG CoA
      reductase. With this approach, the complete loss of copper transport function can
      be ameliorated, as evident from phenotypical improvement in treated Atp7b(-/-)
      mice. This study provides proof of principle for in utero gene therapy in WD and
      other liver-based enzyme deficiencies.

PMID- 22158008
TI  - On the role of ecological adaptation and geographic distribution in the response
      of trees to climate change.

PMID- 22158009
TI  - Fifth International Poplar Symposium: 'Poplars and willows: from research models
      to multipurpose trees for a bio-based society'.
AB  - Carefully managed tree plantations offer an opportunity for sustainable biomass
      production. In recent years, the responses of the Salicaceae to environmental
      constraints have increasingly been investigated at different levels of biological
      integration, giving rise to a physiological approach to the function of trees in
      environmental restoration and monitoring. Significant progress has been achieved
      by the poplar and willow community in understanding targeted characteristics of
      complex tree stress responses. The Fifth International Poplar Symposium brought
      together experts in this area, with the main objective being to improve,
      coordinate and communicate existing national research on the biological and
      environmental dimension of multifunctional poplar and willow plantations. The
      secondary objective was to develop a network of research scientists and extension
      workers to provide scientific support for subjects interested in using fast
      growing poplar and willow species for tree-related environmental projects. The
      ultimate goal was to build up services for the multipurpose tree plantation
      network on local-level management in order to obtain maximized benefits from tree
      crops. The purpose was also to maximize the synergy between local knowledge and
      global-level processes that require information on multipurpose tree crop
      production.

PMID- 22158010
TI  - Nitrogen sources for current-year shoot growth in 50-year-old sessile oak trees:
      an in situ (15)N labeling approach.
AB  - We used long-term in situ (15)N labeling of the soil to investigate the
      contribution of the two main nitrogen (N) sources (N uptake versus N reserves) to
      sun shoot growth from bud burst to full leaf expansion in 50-year-old sessile
      oaks. Recovery of (15)N by growing compartments (leaves, twigs and buds) and
      presence of (15)N in phloem sap were checked weekly. During the first 2 weeks
      following bud burst, remobilized N contributed ~90% of total N in growing leaves
      and twigs. Nitrogen uptake from the soil started concomitantly with N
      remobilization but contributed only slightly to bud burst. However, the fraction
      of total N due to N uptake increased markedly once bud burst had occurred,
      reaching 27% in fully expanded leaves and 18% in developed twigs. In phloem sap,
      the (15)N label appeared a few days after the beginning of labeling and increased
      until the end of bud burst, and then decreased at full leaf expansion in June. Of
      all the shoot compartments, leaves attracted most of the absorbed N, which
      accounted for 68% of new N in shoots, whereas twigs and new buds accounted for
      only 28 and 3%, respectively. New N allocated to leaves increased from unfolding
      to full expansion as total N concentration in the leaves decreased. Our results
      underline the crucial role played by stored N in rapid leaf growth and in the
      sustained growth of oak trees. Any factors that reduce N storage in autumn may
      therefore impair spring shoot growth.

PMID- 22158011
TI  - Relationships between spur- and orchard-level fruit bearing in almond (Prunus
      dulcis).
AB  - Almond is often considered to be a moderately alternate-bearing species but
      historical yield data typically do not exhibit clear patterns of alternate
      bearing at the orchard level, while research has indicated that spurs (the main
      fruit bearing unit in almond trees) rarely produce fruit in two subsequent years.
      The objective of the present work was to analyze the bearing behavior of almond
      trees at both the orchard level and the individual spur level over multiple years
      to explain this apparent paradox. The 10-year yield patterns of three almond
      cultivars grown at three different sites within California were analyzed for
      tendencies of alternate bearing at the orchard level. At the individual spur
      level, data on spur viability, and number of flowers and fruits per spur were
      collected on 2400 individually tagged spurs that were observed over 6 years to
      characterize bearing at that level. At the orchard level one cultivar (Nonpareil)
      did exhibit a tendency for alternate bearing at one site (Kern) but other
      cultivars and sites did not. The orchard and the individual trees in which the
      spur population study was conducted showed tendencies for alternate bearing but
      the spur population did not. Only a relatively small percentage of the total
      tagged spur population bore fruit in any given year and therefore while
      individual fruiting spurs exhibited a high level of non-bearing after fruiting
      the previous year the spurs that did produce fruit in any year generally did not
      constitute enough of the total spur population to exhibit alternate bearing at
      the whole population level. Our results suggest that annual bearing fluctuations
      in almond are probably mainly due to year-to-year variations of parameters
      affecting fruit set and that high rates of fruit set in a given year may involve
      a larger-than-normal percentage of a spur population in fruit bearing. This would
      limit the size of the spur population available for flowering in the subsequent
      year and could cause alternate year bearing. However, from historical records,
      this would appear to be the exception rather than a normal circumstance.
      Therefore, almond should not be considered to be a strictly alternate-bearing
      species.

PMID- 22158013
TI  - Comparison of anterior and lateral approaches in the treatment of extension-type
      supracondylar humerus fractures in children.
AB  - Eighty-four patients who underwent open reduction and Kirschner wire (K-wire)
      fixation for supracondylar humerus fractures through anterior or lateral approach
      with or without additional medial incisions were compared with regard to
      complications and end results. A total of 46 patients were operated through the
      anterior and 38 through the lateral approach. In lateral approach cases, medial
      incision was added only in those patients in whom the medial condyle and
      therefore the ulnar nerve were not easily distinguished due to excessive oedema.
      All the fractures were Gartland type III extension fractures. The patient series
      was consecutive, and lateral approach had a longer follow-up of 89 months (70-134
      months); the incision protocol was changed approximately mid-series to the
      anterior approach, and therefore a shorter follow-up time of only 50 months (24
      84 months) was possible. All patients were treated according to the same
      postoperative protocol. A follow-up examination was performed and all the
      patients were evaluated according to Flynn's criteria; loss of flexion or
      extension clinically, any deviation of the carrying angle radiologically, and the
      appearance of the incision scar were evaluated. According to the above
      parameters, results were excellent in 19, good in 18, and fair in one in the
      lateral incision group, whereas in the anterior incision group, excellent results
      were obtained in 31 patients and good results in 15 of them. Cosmetically, two
      patients in the lateral incision group had hypertrophic scar tissue, whereas the
      anterior incisions were barely noticeable as they were included into the flexion
      crease. In conclusion, we can say that anterior incision when open reduction is
      needed in pediatric supracondylar fractures offer the advantage of a smaller scar
      and easy access to structures that might be injured between the fractured
      fragments.

PMID- 22158015
TI  - Prenatal exposure to maternal obesity leads to hyperactivity in offspring.

PMID- 22158014
TI  - 5-HT(2B) receptors are required for serotonin-selective antidepressant actions.
AB  - The therapeutic effects induced by serotonin-selective reuptake inhibitor (SSRI)
      antidepressants are initially triggered by blocking the serotonin transporter and
      rely on long-term adaptations of pre- and post-synaptic receptors. We show here
      that long-term behavioral and neurogenic SSRI effects are abolished after either
      genetic or pharmacological inactivation of 5-HT(2B) receptors. Conversely, direct
      agonist stimulation of 5-HT(2B) receptors induces an SSRI-like response in
      behavioral and neurogenic assays. Moreover, the observation that (i) this
      receptor is expressed by raphe serotonergic neurons, (ii) the SSRI-induced
      increase in hippocampal extracellular serotonin concentration is strongly reduced
      in the absence of functional 5-HT(2B) receptors and (iii) a selective 5-HT(2B)
      agonist mimics SSRI responses, supports a positive regulation of serotonergic
      neurons by 5-HT(2B) receptors. The 5-HT(2B) receptor appears, therefore, to
      positively modulate serotonergic activity and to be required for the therapeutic
      actions of SSRIs. Consequently, the 5-HT(2B) receptor should be considered as a
      new tractable target in the combat against depression.

PMID- 22158016
TI  - Assessment of a multi-assay, serum-based biological diagnostic test for major
      depressive disorder: a pilot and replication study.
AB  - Despite decades of intensive research, the development of a diagnostic test for
      major depressive disorder (MDD) had proven to be a formidable and elusive task,
      with all individual marker-based approaches yielding insufficient sensitivity and
      specificity for clinical use. In the present work, we examined the diagnostic
      performance of a multi-assay, serum-based test in two independent samples of
      patients with MDD. Serum levels of nine biomarkers (alpha1 antitrypsin,
      apolipoprotein CIII, brain-derived neurotrophic factor, cortisol, epidermal
      growth factor, myeloperoxidase, prolactin, resistin and soluble tumor necrosis
      factor alpha receptor type II) in peripheral blood were measured in two samples
      of MDD patients, and one of the non-depressed control subjects. Biomarkers
      measured were agreed upon a priori, and were selected on the basis of previous
      exploratory analyses in separate patient/control samples. Individual assay values
      were combined mathematically to yield an MDDScore. A 'positive' test, (consistent
      with the presence of MDD) was defined as an MDDScore of 50 or greater. For the
      Pilot Study, 36 MDD patients were recruited along with 43 non-depressed subjects.
      In this sample, the test demonstrated a sensitivity and specificity of 91.7% and
      81.3%, respectively, in differentiating between the two groups. The Replication
      Study involved 34 MDD subjects, and yielded nearly identical sensitivity and
      specificity (91.1% and 81%, respectively). The results of the present study
      suggest that this test can differentiate MDD subjects from non-depressed controls
      with adequate sensitivity and specificity. Further research is needed to confirm
      the performance of the test across various age and ethnic groups, and in
      different clinical settings.

PMID- 22158017
TI  - Speech perception comparisons using an implanted and an external microphone in
      existing cochlear implant users.
AB  - OBJECTIVE: To compare the speech understanding abilities of cochlear implant
      listeners using 2 microphone technologies, the Otologics fully implantable Carina
      and the Cochlear Freedom microphones. STUDY DESIGN: Feasibility study using
      direct comparison of the 2 microphones, nonrandomized and nonblinded within case
      studies. SETTING: Tertiary referral center hospital outpatient clinic. PATIENTS:
      Four subjects with greater than 1 year of unilateral listening experience with
      the Freedom Cochlear Implant and a CNC word score higher than 40%. INTERVENTION:
      A Carina microphone coupled to a percutaneous plug was implanted on the
      ipsilateral side of the cochlear implant. Two months were allowed for healing
      before connecting to the Carina microphone. The percutaneous plug was connected
      to a body worn external processor with output leads inserted into the auxiliary
      port of the Freedom processor. Subjects were instructed to use each of the 2
      microphones for half of their daily implant use. MAIN OUTCOME MEASURES: Aided
      pure tone thresholds, consonant-nucleus-consonant (CNC), Bamford-Kowel-Bench
      Speech in Noise test (BKN-SIN), and Abbreviated Profile of Hearing Aid Benefit.
      RESULTS: All subjects had sound perceptions using both microphones. The loudness
      and quality of the sound was judged to be poorer with the Carina in the first 2
      subjects. The latter 2 demonstrated essential equivalence in the second two
      listeners, with the exception of the Abbreviated Profile of Hearing Aid Benefit
      reporting greater percentage of problems for the Carina in the background noise
      situation for subject 0011-003PP. CNC word scores were better with the Freedom
      than the Carina in all 4 subjects. The latter 2 showed improved speech perception
      abilities with the Carina, compared with the first 2. The BKB-SIN showed
      consistently better results with the Freedom in noise. CONCLUSION: Early
      observations indicate that it is potentially feasible to use the fully implanted
      Carina microphone with the Freedom Cochlear Implant. The authors would anticipate
      that outcomes would improve as more knowledge is gained in signal processing and
      with the fabrication of an integrated device.

PMID- 22158018
TI  - Interaction between electric and acoustic cues in diotic condition for speech
      perception in quiet and noise by cochlear implantees.
AB  - OBJECTIVE: This study aimed to evaluate the interaction of electric and acoustic
      cues in diotic condition in cochlear implantees. MATERIALS AND METHODS: Five
      adult cochlear implantees with residual contralateral hearing were prospectively
      evaluated in hearing aid only (HA), cochlear implant only (CI), and HA + CI modes
      by audiometry (pure tone, dissyllabic words, and sentences), and sound quality
      questionnaires. CI electrodes corresponding to preserved frequencies in the
      contralateral ear (free-field aided thresholds, <50 dB) were then deactivated,
      and patients were retested after 20 to 30 days. RESULTS: Sentences in silence
      showed a benefit of CI and the additive effect of HA + CI. As expected,
      performances with CI alone decreased after apical electrode deactivation. In
      contrast, speech performances (Marginal Benefit from Acoustic Amplification
      sentences) in HA + CI mode were not altered by electrode deactivation in silence
      (90 +/- 5.9% before versus 81 +/- 10.1% after deactivation, not significant, 2
      way analysis of variance) or in noise (78 +/- 4.8% before versus 66 +/- 11.9%
      after deactivation, not significant, 2-way analysis of variance). Performances
      for dissyllabic words confirmed these results. Questionnaires showed a
      significant compensation of partial electrode deactivation by the contralateral
      hearing. Moreover, the human voice was reported to be significantly less
      metallic. CONCLUSION: These results suggested a significant complementarity of
      acoustic and electric diotic cues but also some redundancy affecting the sound
      quality.

PMID- 22158019
TI  - Second-side surgery in superior canal dehiscence syndrome.
AB  - OBJECTIVE: Bilateral superior canal (SC) dehiscence syndrome poses a challenge
      because bilateral SC dehiscence (SCD) plugging might be expected to result in
      oscillopsia and disability. Our aims were as follows: 1) to evaluate which
      symptoms prompted patients with bilateral SCD syndrome (SCDS) to seek second-side
      surgery, and 2) to determine the prevalence of disabling imbalance and
      oscillopsia after bilateral SC plugging. STUDY DESIGN: Prospective observational
      study. SETTING: Tertiary referral center. PATIENTS: Five patients with bilateral
      SCDS based on history, audiometric and physiologic testing, and computed
      tomographic findings. This includes all of our patients who have had second-side
      plugging surgery to date. INTERVENTION(S): Bilateral sequential middle fossa
      craniotomy and plugging of SCs. MAIN OUTCOME MEASURE(S): Cochleovestibular
      symptoms, cervical and ocular vestibular-evoked myogenic potential testing,
      dizziness handicap inventory, short-form 36 Health Survey, dynamic visual acuity
      testing. RESULTS: The most common symptoms prompting second-side surgery were
      sound- and pressure-induced vertigo and autophony. Three of the 5 patients
      reported that symptoms shifted to the contralateral ear immediately after
      plugging the first side, whereas in 2 patients, contralateral symptoms developed
      several years after the first SC plugging. Two of 4 patients experienced ongoing
      oscillopsia after bilateral SCDS surgery; however, all patients reported relief
      from their SCD symptoms and were glad that they had pursued bilateral surgery.
      CONCLUSION: In patients with bilateral SCDS, sound- and pressure-induced vertigo
      most commonly prompted second-side surgery. Despite some degree of oscillopsia
      after bilateral SCDS surgery, patients were very satisfied with second-side
      surgery, given their relief from other SCDS symptoms.

PMID- 22158021
TI  - Cancer genomics: Finding a rare variant.

PMID- 22158020
TI  - A cell culture model of facial palsy resulting from reactivation of latent herpes
      simplex type 1.
AB  - HYPOTHESIS: Reactivation of herpes simplex virus type 1 (HSV-1) in geniculate
      ganglion neurons (GGNs) is an etiologic mechanism of Bell's palsy (BP) and
      delayed facial palsy (DFP) after otologic surgery. BACKGROUND: Several clinical
      studies, including temporal bone studies, antibody, titers, and intraoperative
      studies, suggest that reactivation of HSV-1 from latently infected GGNs may lead
      to both BP and DFP. However, it is difficult to study these processes in humans
      or live animals. METHODS: Primary cultures of GGNs were latently infected with
      Patton strain HSV-1 expressing a green fluorescent protein-late lytic gene
      chimera. Four days later, these cultures were treated with trichostatin A (TSA),
      a known chemical reactivator of HSV-1 in other neurons. Cultures were monitored
      daily by fluorescent microscopy. Titers of media from lytic, latent, and
      latent/TSA treated GGN cultures were obtained using plaque assays on Vero cells.
      RNA was harvested from latently infected GGN cultures and examined for the
      presence of viral transcripts using reverse transcription-polymerase chain
      reaction. RESULTS: Latently infected GGN cultures displayed latency-associated
      transcripts only, whereas lytically infected and reactivated latent cultures
      produced other viral transcripts, as well. The GGN cultures displayed a
      reactivation rate of 65% after treatment with TSA. Media from latently infected
      cultures contained no detectable infectious HSV-1, whereas infectious virus was
      observed in both lytically and latently infected/TSA-treated culture media.
      CONCLUSION: We have shown that cultured GGNs can be latently infected with HSV-1,
      and HSV-1 in these latently infected neurons can be reactivated using TSA,
      yielding infectious virus. These results have implications for the cause of both
      BP and DFP.

PMID- 22158023
TI  - Biomarkers: Major mathematical hurdles for biomarker-based screening.

PMID- 22158022
TI  - Programmed cell removal: a new obstacle in the road to developing cancer.
AB  - The development of cancer involves mechanisms by which aberrant cells overcome
      normal regulatory pathways that limit their numbers and their migration. The
      evasion of programmed cell death is one of several key early events that need to
      be overcome in the progression from normal cellular homeostasis to malignant
      transformation. Recently, we provided evidence in mouse and human cancers that
      successful cancer clones must also overcome programmed cell removal. In this
      Opinion article, we explore the role of programmed cell removal in both normal
      and neoplastic cells, and we place this pathway in the context of the initiation
      of programmed cell death.

PMID- 22158024
TI  - Determining cell number during cell culture using the Scepter cell counter.
AB  - Counting cells is often a necessary but tedious step for in vitro cell culture.
      Consistent cell concentrations ensure experimental reproducibility and accuracy.
      Cell counts are important for monitoring cell health and proliferation rate,
      assessing immortalization or transformation, seeding cells for subsequent
      experiments, transfection or infection, and preparing for cell-based assays. It
      is important that cell counts be accurate, consistent, and fast, particularly for
      quantitative measurements of cellular responses. Despite this need for speed and
      accuracy in cell counting, 71% of 400 researchers surveyed(1) who count cells
      using a hemocytometer. While hemocytometry is inexpensive, it is laborious and
      subject to user bias and misuse, which results in inaccurate counts.
      Hemocytometers are made of special optical glass on which cell suspensions are
      loaded in specified volumes and counted under a microscope. Sources of errors in
      hemocytometry include: uneven cell distribution in the sample, too many or too
      few cells in the sample, subjective decisions as to whether a given cell falls
      within the defined counting area, contamination of the hemocytometer, user-to
      user variation, and variation of hemocytometer filling rate(2). To alleviate the
      tedium associated with manual counting, 29% of researchers count cells using
      automated cell counting devices; these include vision-based counters, systems
      that detect cells using the Coulter principle, or flow cytometry(1).  For most
      researchers, the main barrier to using an automated system is the price
      associated with these large benchtop instruments(1). The Scepter cell counter is
      an automated handheld device that offers the automation and accuracy of Coulter
      counting at a relatively low cost. The system employs the Coulter principle of
      impedance-based particle detection(3) in a miniaturized format using a
      combination of analog and digital hardware for sensing, signal processing, data
      storage, and graphical display. The disposable tip is engineered with a
      microfabricated, cell- sensing zone that enables discrimination by cell size and
      cell volume at sub-micron and sub-picoliter resolution. Enhanced with precision
      liquid-handling channels and electronics, the Scepter cell counter reports cell
      population statistics graphically displayed as a histogram.

PMID- 22158025
TI  - Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner
      of genetic mutations.
AB  - OBJECTIVES: The role of pancreas divisum (PD) as a cause of acute recurrent or
      chronic pancreatitis (AR/CP) is still a matter of debate. METHODS: The aims of
      this study were to evaluate the frequency of PD diagnosed using magnetic
      resonance cholangiopancreatography (MRCP) in patients with AR/CP of unknown
      origin (n=40) after careful exclusion of all known causes and to test the
      hypothesis of an interaction between anatomical (PD) and functional genetic
      anomalies (SPINK1, PRSS1, or CFTR gene mutations or polymorphisms (n=19, 25, and
      30, respectively)) that could result in AR/CP. Patients with alcohol-induced
      pancreatitis (n=29) and subjects who had MRCP for a nonpancreatic disease (n=45)
      served as controls. RESULTS: PD frequency was 7% in subjects without pancreatic
      disease, 7% in patients with alcohol-induced pancreatitis, and 5, 16, 16, and 47%
      in those with idiopathic, and PRSS1-, SPINK1-, and CFTR-associated pancreatitis,
      respectively (P<0.0001). There was no significant difference between idiopathic
      pancreatitis and the two control groups. The frequency of PD was higher in
      patients with CFTR gene-associated pancreatitis as compared with those with
      idiopathic and alcoholic pancreatitis (P<0.0001) and with those with SPINK1 and
      PRSS1 gene-associated pancreatitis (P<0.02). CONCLUSIONS: The frequency of PD was
      not different in patients with idiopathic pancreatitis as compared with controls,
      demonstrating that PD by itself is not a cause of pancreatitis. PD frequency was
      higher in patients with genetic pancreatitis, especially in those with CFTR
      mutations or polymorphisms, suggesting a cumulative effect of these two
      cofactors.

PMID- 22158027
TI  - Clinical and genetic risk factors for perianal Crohn's disease in a population
      based cohort.
AB  - OBJECTIVES: Perianal Crohn's disease (CD) affects around one-quarter of CD
      patients and represents a distinct disease phenotype. The objective of this study
      was to investigate a large population-based cohort of inflammatory bowel disease
      (IBD) patients to identify clinical and genetic risk factors for perianal CD.
      METHODS: Data were collected in the Canterbury IBD database, estimated to include
      91% of all patients with IBD in Canterbury, New Zealand. Genotyping was performed
      for selected loci previously demonstrated to be associated with CD. Patients with
      perianal disease were then compared with both CD patients without perianal
      disease and healthy controls to assess the presence of potential phenotypic,
      environmental, and genetic risk factors. RESULTS: Of the 715 CD patients in the
      database, 190 (26.5%) had perianal disease. In all, 507 patients with genotype
      data available were analyzed. Perianal disease was associated with younger age at
      diagnosis (P < 0.0001), complicated intestinal disease (P < 0.0001), and ileal
      disease location (P = 0.002). There was no association with gender, ethnicity,
      smoking, or breast feeding. Genotype analysis revealed an association with the
      neutrophil cytosolic factor 4 (NCF4) gene compared with both non-perianal CD
      patients (odds ratio (OR): 1.47; 95% confidence interval (CI): 1.08-1.99) and
      healthy controls (OR: 1.47; 95% CI: 1.10-1.95). There was no association
      identified with other genes, including IBD5 (OR: 0.91; 95% CI: 0.69-1.20), tumor
      necrosis factor alpha (OR: 1.04; 95% CI: 0.56-1.85), and IRGM (immunity-related
      guanosine triphosphatase protein type M) (OR: 1.21; 95% CI: 0.80-1.82).
      CONCLUSIONS: This study suggests that younger age at diagnosis, complicated
      disease behavior, and ileal disease location are risk factors for perianal CD. In
      addition, this paper represents the first report of an association of the NCF4
      gene with perianal disease.

PMID- 22158026
TI  - Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and
      prognostic factors.
AB  - OBJECTIVES: Radiofrequency ablation (RFA) is widely performed for hepatocellular
      carcinoma (HCC). However, there has been no report on 10-year outcome of RFA. The
      objective of this study was to report a 10-year consecutive case series at a
      tertiary referral center. METHODS: We performed 2,982 RFA treatments on 1,170
      primary HCC patients and analyzed a collected database. RESULTS: Final computed
      tomography images showed complete tumor ablation in 2,964 (99.4%) of 2,982
      treatments performed for the 1,170 primary HCC patients. With a median follow-up
      of 38.2 months, 5- and 10-year survival rates were 60.2% (95% confidence interval
      (CI): 56.7-63.9%) and 27.3% (95% CI: 21.5-34.7%), respectively. Multivariate
      analysis demonstrated that age, antibody to hepatitis C virus (anti-HCV), Child
      Pugh class, tumor size, tumor number, serum des-gamma-carboxy-prothrombin (DCP)
      level, and serum lectin-reactive alpha-fetoprotein level (AFP-L3) were
      significantly related to survival. Five- and 10-year local tumor progression
      rates were both 3.2% (95% CI: 2.1-4.3%). Serum DCP level alone was significantly
      related to local tumor progression. Five- and 10-year distant recurrence rates
      were 74.8% (95% CI: 71.8-77.8%) and 80.8% (95% CI: 77.4-84.3%), respectively.
      Anti-HCV, Child-Pugh class, platelet count, tumor size, tumor number, serum AFP
      level, and serum DCP level were significantly related to distant recurrence.
      There were 67 complications (2.2%) and 1 death (0.03%). CONCLUSIONS: RFA could be
      locally curative for HCC, resulting in survival for as long as 10 years, and was
      a safe procedure. RFA might be a first-line treatment for selected patients with
      early-stage HCC.

PMID- 22158029
TI  - Sleep deprivation and sleep recovery modifies connexin36 and connexin43 protein
      levels in rat brain.
AB  - Gap junctional communication is mainly mediated by connexin36 and connexin43 in
      neurons and astrocytes, respectively. It has been suggested that connexin36
      allows electrical coupling between neurons whereas connexin43 participates in
      several process including release of ATP. It was recently reported that blockage
      of gap junctional communication mediated by connexin36 can disrupt the sleep
      architecture of the rat. However, there is no experimental approach about effects
      of sleep deprivation on connexins expression. Therefore, we examined in adult
      male Wistar rats whether protein levels of connexin36 and connexin43 change in
      pons, hypothalamus, and frontal cortex after 24 h of total sleep deprivation and
      4 h of sleep recovery. Western blot revealed that total sleep deprivation
      significantly decreases the levels of connexin36 in the hypothalamus and this
      decrease maintains after sleep recovery. Meanwhile, connexin43 is not altered by
      total sleep deprivation but interestingly the sleep recovery period induces an
      increase of this connexin. These results suggest that electrical coupling between
      hypothalamic neurons could be altered by sleep deprivation and that sleep
      recovery drives changes in connexin43 expression probably as a mechanism related
      to ATP release and energy regulation during sleep.

PMID- 22158030
TI  - Non-coding RNAs and the advent of new directions in therapeutics.

PMID- 22158028
TI  - Serum and colonic mucosal immune markers in irritable bowel syndrome.
AB  - OBJECTIVES: Low-grade colonic mucosal inflammation has been postulated to have an
      important role in the pathophysiology of irritable bowel syndrome (IBS). The
      objectives of this study were (i) to identify serum and tissue-based
      immunological and neuroendocrine markers associated with mucosal inflammation in
      male (M) and female (F) patients with non-post-infectious IBS (non-PI-IBS)
      compared with healthy controls and (ii) to assess possible correlations of such
      markers with IBS symptoms. METHODS: Sigmoid mucosal biopsies were obtained from
      45 Rome II positive IBS patients without a history of PI-IBS (26 F, 35.5% IBS-C,
      33.3% IBS-D, 31.1% IBS-A/M) and 41 healthy controls (22 F) in order to measure
      immunological markers (serum cytokine levels, colonic mucosal mRNA levels of
      cytokines, mucosal immune cell counts) and neuroendocrine markers associated with
      mucosal inflammation (corticotropin releasing factor- and neurokinin (NK)-related
      ligands and receptors, enterochromaffin cells). Symptoms were measured using
      validated questionnaires. RESULTS: Of all the serum and mucosal cytokines
      measured, only interleukin-10 (IL-10) mRNA expression showed a group difference,
      with female, but not male, patients showing lower levels compared with female
      controls (18.0+/-2.9 vs. 29.5+/-4.0, P=0.006). Mucosal mRNA expression of NK-1
      receptor was significantly lower (1.15+/-0.19 vs. 2.66+/-0.56, P=0.008) in
      female, but not male, patients compared with healthy controls. No other
      significant differences were observed. CONCLUSIONS: Immune cell counts and levels
      of cytokines and neuropeptides that are associated with inflammation were not
      significantly elevated in the colonic mucosa of non-PI-IBS patients, and did not
      correlate with symptoms. Thus, these findings do not support that colonic mucosal
      inflammation consistently has a primary role in these patients. However, the
      finding of decreased IL-10 mRNA expression may be a possible biomarker of IBS and
      warrants further investigation.

PMID- 22158031
TI  - Using non-coding small RNAs to develop therapies for Huntington's disease.
AB  - Huntington's disease (HD) is caused by an expansion of CAG triplets at the 5' end
      of the HD gene, which encodes a pathologically elongated polyglutamine stretch
      near the N-terminus of huntingtin. HD is an incurable autosomal-dominant
      neurodegenerative disease characterized by movement disorder, as well as
      emotional distress and dementia. The newly discovered roles of the non-coding
      small RNAs in specific degradation or translational suppression of the targeted
      mRNAs suggest a potential therapeutic approach of post-transcriptional gene
      silencing that targets the underlying disease etiology rather than the downstream
      pathological consequences. From pre-clinical trials in different HD animal models
      to cells from HD patients, small RNA interference has been applied to 'allele-non
      specifically or allele-specifically' silence the mutant HD transgene or
      endogenous mutant HD allele. Silencing the mutant HD transgene significantly
      inhibits neurodegeneration, improves motor control, and extends survival of HD
      mice. With future improvement of mutant allele selectivity (preserving the
      expression of the neuroprotective wild-type allele), target specificity, efficacy
      and safety, as well as optimization of delivery methods, small non-coding RNA
      based therapeutic applications will be a promising approach to treat HD.

PMID- 22158033
TI  - Involvement of the SKP2-p27(KIP1) pathway in suppression of cancer cell
      proliferation by RECK.
AB  - The membrane-anchored matrix metalloproteinase-regulator RECK is often
      downregulated in cancers; in some cases, a significant correlation between the
      level of residual RECK in resected tumors and patient survival has been noted.
      Furthermore, restoration of RECK expression in certain cancer-derived cell lines
      results in reduced tumorigenicity. Here we report that acute RECK expression in
      colon carcinoma cells results in cell cycle-arrest accompanied by downregulation
      of a ubiquitin ligase component, S-phase kinase-associated protein 2 (SKP2), and
      upregulation of its substrate, p27(KIP1). Our data indicate that RECK-induced
      growth suppression is at least partially dependent on p27, and that RECK and type
      I collagen share similar effects on the SKP2-p27 pathway. Importantly, in
      patients with lung, colorectal and bladder cancers, the RECK/SKP2 ratio is high
      in normal tissues and lower in the cancer tissues. These findings reveal a novel
      molecular pathway linking cell-cycle progression to RECK downregulation,
      extracellular matrix degradation and SKP2 upregulation, and suggest that
      treatment regimens that induce RECK expression could be promising cancer
      therapies.

PMID- 22158034
TI  - Akt2 interacts with Snail1 in the E-cadherin promoter.
AB  - Snail1 is a transcriptional factor essential for triggering epithelial-to
      mesenchymal transition. Moreover, Snail1 promotes resistance to apoptosis, an
      effect associated to PTEN gene repression and Akt stimulation. In this article we
      demonstrate that Snail1 activates Akt at an additional level, as it directly
      binds to and activates this protein kinase. The interaction is observed in the
      nucleus and increases the intrinsic Akt activity. We determined that Akt2 is the
      isoform interacting with Snail1, an association that requires the pleckstrin
      homology domain in Akt2 and the C-terminal half in Snail1. Snail1 enhances the
      binding of Akt2 to the E-cadherin (CDH1) promoter and Akt2 interference prevents
      Snail1 repression of CDH1 gene. We also show that Snail1 binding increases Akt2
      intrinsic activity on histone H3 and have identified Thr45 as a residue modified
      on this protein. Phosphorylation of Thr45 in histone H3 is sensitive to Snail1
      and Akt2 cellular levels; moreover, Snail1 upregulates the binding of
      phosphoThr45 histone H3 to the CDH1 promoter. These results uncover an unexpected
      role of Akt2 in transcriptional control and point out to phosphorylation of Thr45
      in histone H3 as a new epigenetic mark related to Snail1 and Akt2 action.

PMID- 22158035
TI  - Proyl isomerase Pin1 facilitates ubiquitin-mediated degradation of cyclin
      dependent kinase 10 to induce tamoxifen resistance in breast cancer cells.
AB  - Endocrine therapies that inhibit estrogen receptor (ER)-alpha signaling are the
      most common and effective treatment for ER-alpha-positive breast cancer. However,
      the use of these agents is limited by the frequent development of resistance. The
      aim of this study was to elucidate the mechanisms by which downregulation of
      CDK10 expression confers resistance to tamoxifen in breast cancer. Here, we show
      that peptidyl-prolyl isomerase Pin1 downregulates CDK10 protein as a result of
      its interaction with and ubiquitination of CDK10, thereby affecting CDK10
      dependent Raf-1 phosphorylation (S338). Pin1(-/-) mouse embryonic fibroblasts
      (MEFs) show higher CDK10 expression than Pin1(+/+) MEFs, whereas CDK10 protein
      was downregulated in the rescued Pin1(-/-) MEFs after reexpression of Pin1. Pin1
      silencing in SKBR-3 and MCF7 cells increased the CDK10 expression. In human
      tamoxifen-resistant breast cancer and tamoxifen-resistant MCF7 cells,
      immunohistochemical staining and immunoblotting analysis shows an inverse
      correlation between the expression of CDK10 and the degree of tamoxifen
      resistance. There was also a positive correlation between the high level of P-Raf
      1 (Ser338) and Pin1 in human tamoxifen-resistant breast cancer and tamoxifen
      resistant MCF7 (TAMR-MCF7) cells. Importantly, 4-OH tamoxifen (4-OHT), when used
      in combination with overexpressed CDK10 or Raf-1 inhibitor, increased cleaved
      PARP and DNA fragmentation to inhibit cologenic growth of MCF7 cells and
      Tamoxifen-resistant MCF7 cells, respectively. On the basis of these findings, we
      suggest that the Pin1-mediated CDK10 ubiquitination is a major regulator of
      tamoxifen-resistant breast cancer cell growth and survival.

PMID- 22158036
TI  - Thiazolide-induced apoptosis in colorectal cancer cells is mediated via the Jun
      kinase-Bim axis and reveals glutathione-S-transferase P1 as Achilles' heel.
AB  - Glutathione-S-transferase of the Pi class (GSTP1) is frequently overexpressed in
      a variety of solid tumors and has been identified as a potential therapeutic
      target for cancer therapy. GSTP1 is a phase II detoxification enzyme and
      conjugates the tripeptide glutathione to endogenous metabolites and xenobiotics,
      thereby limiting the efficacy of antitumor chemotherapeutic treatments. In
      addition, GSTP1 regulates cellular stress responses and apoptosis by sequestering
      and inactivating c-Jun N-terminal kinase (JNK). Thiazolides are a novel class of
      antibiotics for the treatment of intestinal pathogens with no apparent side
      effects on the host cells and tissue. Here we show that thiazolides induce a
      GSTP1-dependent and glutathione-enhanced cell death in colorectal tumor cell
      lines. Downregulation of GSTP1 reduced the apoptotic activity of thiazolides,
      whereas overexpression enhanced it. Thiazolide treatment caused strong Jun kinase
      activation and Jun kinase-dependent apoptosis. As a critical downstream target of
      Jun kinase we identified the pro-apoptotic Bcl-2 homolog Bim. Thiazolides induced
      Bim expression and activation in a JNK-dependent manner. Downregulation of Bim in
      turn significantly blocked thiazolide-induced apoptosis. Whereas low
      concentrations of thiazolides failed to induce apoptosis directly, they potently
      sensitized colon cancer cells to TNF-related apoptosis-inducing ligand- and
      chemotherapeutic drug-induced cell death. Although GSTP1 overexpression generally
      limits chemotherapy and thus antitumor treatment, our study identifies GSTP1 as
      Achilles' heel and thiazolides as novel interesting apoptosis sensitizer for the
      treatment of colorectal tumors.

PMID- 22158037
TI  - Sprouty1 is a candidate tumor-suppressor gene in medullary thyroid carcinoma.
AB  - Medullary thyroid carcinoma (MTC) is a malignancy derived from the calcitonin
      producing C-cells of the thyroid gland. Oncogenic mutations of the Ret proto
      oncogene are found in all heritable forms of MTC and roughly one half of the
      sporadic cases. However, several lines of evidence argue for the existence of
      additional genetic lesions necessary for the development of MTC. Sprouty (Spry)
      family of genes is composed of four members in mammals (Spry1-4). Some Spry
      family members have been proposed as candidate tumor-suppressor genes in a
      variety of cancerous pathologies. In this work, we show that targeted deletion of
      Spry1 causes C-cell hyperplasia, a precancerous lesion preceding MTC, in young
      adult mice. Expression of Spry1 restrains proliferation of the MTC-derived cell
      line, TT. Finally, we found that the Spry1 promoter is frequently methylated in
      MTC and that Spry1 expression is consequently decreased. These findings identify
      Spry1 as a candidate tumor-suppressor gene in MTC.

PMID- 22158038
TI  - Mcm2 deficiency results in short deletions allowing high resolution
      identification of genes contributing to lymphoblastic lymphoma.
AB  - Mini-chromosome maintenance (Mcm) proteins are part of the replication-licensing
      complex that is loaded onto chromatin during the G1-phase of the cell cycle and
      required for initiation of DNA replication in the subsequent S-phase. Mcm
      proteins are typically loaded in excess of the number of locations that are used
      during S-phase. Nonetheless, partial depletion of Mcm proteins leads to cancers
      and stem cell deficiencies. Mcm2 deficient mice, on a 129Sv genetic background,
      display a high rate of thymic lymphoblastic lymphoma. Here array comparative
      genomic hybridization is used to characterize the genetic damage accruing in
      these tumors. The predominant events are deletions averaging less than 0.5 Mbp,
      considerably shorter than observed in prior studies using alternative mouse
      lymphoma models or human tumors. Such deletions facilitate identification of
      specific genes and pathways responsible for the tumors. Mutations in many genes
      that have been implicated in human lymphomas are recapitulated in this mouse
      model. These features, and the fact that the mutation underlying the accelerated
      genetic damage does not target a specific gene or pathway a priori, are valuable
      features of this mouse model for identification of tumor suppressor genes. Genes
      affected in all tumors include Pten, Tcfe2a, Mbd3 and Setd1b. Notch1 and
      additional genes are affected in subsets of tumors. The high frequency of
      relatively short deletions is consistent with elevated recombination between
      nearby stalled replication forks in Mcm2-deficient mice.

PMID- 22158039
TI  - The insulin resistance Grb14 adaptor protein promotes thyroid cancer ret
      signaling and progression.
AB  - The growth factor receptor-bound protein (Grb) 14 is an adaptor molecule of the
      Grb7/10/14 family with characteristic Between Plekstrin and SH2 (BPS) domains
      serving to avidly bind tyrosine kinases. Grb14 inhibits insulin receptor (IR)
      catalytic activity through interaction with the BPS domain and impedes peptide
      substrate binding. Members of this Grb family have also been shown to interact
      with other kinases through their SH2 domain. Here we examined the functional role
      of Grb14 in thyroid cancer using loss- and gain-of-function approaches. Stable
      knockdown of Grb14 in thyroid cancer cells facilitated IR signaling. In contrast,
      RET phosphorylation was diminished in concert with reduced activation of Akt and
      signal transducer and activator of transcription 3 (STAT3). Loss of Grb14 also
      resulted in diminished cell proliferation and invasion both in vitro and in mouse
      flank xenografts. In complementary studies, forced expression of Grb14
      interrupted IR signaling but facilitated RET activation, STAT3 and Akt
      phosphorylation. Consistent with these findings Grb14 overexpression enhanced
      cell invasion and resulted in striking metastases in an orthotopic thyroid cancer
      mouse xenograft model. Primary human thyroid cancer microarrays revealed a
      positive correlation between Grb14 expression and invasive behavior. Our findings
      uncover a new role for Grb14 in finely tuning receptor signaling and modulating
      thyroid cancer progression.

PMID- 22158040
TI  - Sp1 expression regulates lung tumor progression.
AB  - The role of specificity protein 1 (Sp1) in controlling gene expression in lung
      tumor development and metastasis is not well understood. In this study, we showed
      that the Sp1 level was highly increased and required for lung tumor growth in
      transgenic mice bearing Kras-induced lung tumors under the control of
      doxycycline. Furthermore, the Sp1 level was highly upregulated in lung
      adenocarcinoma cells with low invasiveness and in patients with stage I lung
      cancer. We also demonstrated that Sp1 was downregulated in lung adenocarcinoma
      cells with high invasiveness and in patients with stage IV lung adenocarcinoma.
      Moreover, Sp1 inversely regulated migration, invasion and metastasis of lung
      adenocarcinoma cells in vivo. In addition, a decrease in the Sp1 level in highly
      invasive lung adenocarcinoma cells resulted from instability of the Sp1 protein.
      Furthermore, overexpression of Sp1 in highly invasive lung adenocarcinoma cells
      increased expression of E-cadherin, a suppressor of metastasis, and attenuated
      the translocation of beta-catenin into the cellular nucleus that leads to tumor
      malignancy. Taken together, Sp1 level accumulated strongly in early stage and
      then declined in late stage, which is important for lung cancer cell
      proliferation and metastasis during tumorigenesis.

PMID- 22158042
TI  - Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q
      deleted oligodendroglial tumours and increases radio- and chemosensitivity of
      Hs683 glioma cells in vitro.
AB  - Deletions of chromosomal arms 1p and 19q are frequent in oligodendroglial tumours
      and linked to radio- and chemotherapy response as well as longer survival. The
      molecular mechanisms underlying this clinically important association are as yet
      unknown. Here, we studied the peroxiredoxin 1 (PRDX1) gene at 1p34.1 for promoter
      methylation and expression in primary gliomas and investigated its role in radio-
      and chemosensitivity of glioma cells in vitro. In total, we screened primary
      glioma tissues from 93 patients for methylation of the 5'-CpG island of PRDX1 by
      sodium bisulfite sequencing. PRDX1 mRNA and protein expression levels were
      determined in subsets of the tumours by quantitative PCR and western blot
      analysis, respectively. PRDX1 hypermethylation and reduced expression were
      frequently detected in oligodendroglial tumours and secondary glioblastomas, but
      not in primary glioblastomas. In oligodendroglial tumours, both PRDX1
      hypermethylation and reduced mRNA expression were significantly associated with
      1p/19q-deletion. Stable knockdown of PRDX1 by lentiviral transduction of short
      hairpin (sh)RNA constructs significantly increased apoptosis and reduced cell
      viability of Hs683 glioma cells exposed to ionizing irradiation or temozolomide
      in vitro. Taken together, our findings indicate that epigenetic silencing of
      PRDX1 is frequent in 1p/19q-deleted oligodendroglial tumours and likely
      contributes to radio- and chemosensitivity of these tumours.

PMID- 22158041
TI  - A p27Kip1 mutant that does not inhibit CDK activity promotes centrosome
      amplification and micronucleation.
AB  - Mitotic catastrophe occurs when cells enter mitosis with damaged DNA or excess
      centrosomes. Cells overexpressing the centrosome protein CP110 or depleted of
      cyclin F, which targets CP110 for destruction, have more than two centrosomes and
      undergo mitotic catastrophe. Our studies show centrosome reduplication and
      mitotic catastrophe in osteosarcoma cells inducibly expressing a p27Kip1 mutant
      (termed p27K) that binds cyclins but not cyclin-dependent kinases (CDKs). p27K
      inhibited cell proliferation but not CDK activity or cell cycle progression. It
      did not induce apoptosis; however, cells expressing p27K had more than two
      centrosomes and, indicative of mitotic catastrophe, irregularly shaped nuclei or
      multiple micronuclei. p27K interacted with cyclin F in vivo (as did endogenous
      p27Kip1) and displaced cyclin F from CP110. Depletion of CP110 rescued p27K
      expressing cells from centrosome reduplication and mitotic catastrophe.
      Collectively, our data show that p27Kip1 can perturb mitosis and suggest that it
      does so by sequestering cyclin F, which prevents its interaction with and the
      subsequent degradation of CP110, ultimately resulting in centrosome
      reduplication, mitotic catastrophe and abrogation of cell proliferation.

PMID- 22158043
TI  - A novel function for platelet-derived growth factor D: induction of osteoclastic
      differentiation for intraosseous tumor growth.
AB  - Although increasing evidence suggests a critical role for platelet-derived growth
      factor (PDGF) receptor beta (beta-PDGFR) signaling in prostate cancer (PCa)
      progression, the precise roles of beta-PDGFR and PDGF isoform-specific cell
      signaling have not been delineated. Recently, we identified the PDGF-D isoform as
      a ligand for beta-PDGFR in PCa and showed that PDGF-D is activated by serine
      protease-mediated proteolytic removal of the CUB domain in a two-step process,
      yielding first a hemidimer (HD) and then a growth factor domain dimer. Herein, we
      demonstrate that the expression of PDGF-D in human PCa LNCaP cells leads to
      enhanced bone tumor growth and bone responses in immunodeficient mice.
      Histopathological analyses of bone tumors generated by PDGF-D-expressing LNCaP
      cells (LNCaP-PDGF-D) revealed osteolytic and osteoblastic responses similar to
      those observed in human PCa bone metastases. Importantly, we discovered a novel
      function of PDGF-D in the regulation of osteoclast differentiation, independent
      of the RANKL/RANK signaling axis. Although both PDGF-B and -D were able to
      activate beta-PDGFR, only PDGF-D was able to induce osteoclastic differentiation
      in vitro, and upregulate the expression and nuclear translocation of nuclear
      factor of activated T cells 1, a master transcription factor for
      osteoclastogenesis. Taken together, these results reveal a new function of PDGF-D
      as a regulator of osteoclastic differentiation, an activity critical for the
      establishment of skeletal metastatic deposit in PCa patients.

PMID- 22158044
TI  - N-cadherin haploinsufficiency increases survival in a mouse model of pancreatic
      cancer.
AB  - Pancreatic ductal adenocarcinoma (PDA) is often detected at a late stage, hence
      the identification of new therapies that have potential to block tumor
      progression is critical for this lethal disease. N-cadherin upregulation has been
      observed in many cancers including PDA, however, a causal role for this cell
      adhesion receptor in disease progression has yet to be defined. The concomitant
      expression of oncogenic Kras(G12D) and mutant p53 (Trp53(R172H)) in the murine
      pancreas results in metastatic PDA that recapitulates the cognate features of
      human pancreatic cancer providing an excellent animal model to identify genes
      required for tumor progression. Here we determine the consequences of genetically
      manipulating N-cadherin expression in a mouse model of PDA. Remarkably, mice with
      reduced N-cadherin expression (that is, Ncad(-/+)) survived 25% longer (177 vs
      142 days, P<0.05) than animals expressing two wild-type N-cadherin (Cdh2)
      alleles. The survival benefit is likely due to a cumulative effect of N
      cadherin's role in different aspects of tumorigenesis including tumor-cell
      survival, growth, migration and invasion. Interestingly, reduced hedgehog
      signaling may contribute to the better prognosis for the Ncad(-/+) mice.
      Moreover, the matrix metalloproteinase MMP-7, associated with poor prognosis in
      PDA, was reduced in Ncad(-/+) tumors. Finally, Ncad(-/+) tumor cells exhibited
      decreased FGF-stimulated ERK1/2 activation consistent with N-cadherin's ability
      to promote FGFR signaling. These data support a critical role for N-cadherin in
      PDA and its potential prognostic value. Additionally, this study provides in vivo
      genetic evidence that the cell-surface protein N-cadherin represents a promising
      therapeutic target for the treatment of pancreatic cancer.

PMID- 22158045
TI  - SULF2 methylation is prognostic for lung cancer survival and increases
      sensitivity to topoisomerase-I inhibitors via induction of ISG15.
AB  - The heparan sulfate 6-O-endosulfatase (SULF2) promotes growth and metastasis of
      solid tumors. We recently identified that cytosine methylation of the SULF2
      promoter is associated with better survival of resected lung adenocarcinoma
      patients, and now also demonstrates a marginal improvement in survival of
      advanced non-small cell lung cancer (NSCLC) patients receiving standard
      chemotherapy (hazard ratio=0.63, P=0.07). Subsequent studies focused on
      investigating the effect of methylation on SULF2 expression and its genome-wide
      impact. The genes and pathways modulated by epigenetic inactivation of SULF2 and
      the effects on sensitivity to chemotherapy were characterized in vitro and in
      vivo. Silencing SULF2 through small interfering RNA or methylation primarily
      increased expression of interferon-inducible genes including ISG15, a marker for
      increased sensitivity to topoisomerase-1 inhibitors such as camptothecin (CPT).
      NSCLC cell lines with methylated SULF2 (SULF2M) express 60-fold higher ISG15
      compared with SULF2 unmethylated (SULF2U) NSCLC cell lines and normal human
      bronchial epithelial cells. In vitro, SULF2M and high ISG15 (ISG15H)-expressing
      NSCLC cell lines were 134-fold more sensitive to CPT than SULF2U and low ISG15
      (ISG15L)-expressing cell lines. Topotecan, a soluble analog of CPT and FDA
      approved anticancer drug, dramatically arrested the growth of SULF2M-ISG15H, but
      not SULF2U-ISG15L lung tumors in nude mice (P<0.002). Similarly, high ISG15
      expression that is comparable to the topotecan (TPT)-sensitive NSCLC cell lines
      was found in tumors from 25% of NSCLC patients compared with normal lung,
      indicating a potential to identify and target the most sensitive NSCLC
      subpopulation for personalized TPT therapy.

PMID- 22158046
TI  - Ligand-dependent EGFR activation induces the co-expression of IL-6 and PAI-1 via
      the NFkB pathway in advanced-stage epithelial ovarian cancer.
AB  - The epidermal growth factor receptor (EGFR), a member of the ErbB family of
      receptor tyrosine kinases, is expressed in up to 70% of epithelial ovarian
      cancers (EOCs), where it correlates with poor prognosis. The majority of EOCs are
      diagnosed at an advanced stage, and at least 50% present malignant ascites. High
      levels of IL-6 have been found in the ascites of EOC patients and correlate with
      shorter survival. Herein, we investigated the signaling cascade led by EGFR
      activation in EOC and assessed whether EGFR activation could induce an EOC
      microenvironment characterized by pro-inflammatory molecules. In vitro analysis
      of EOC cell lines revealed that ligand-stimulated EGFR activated NFkB-dependent
      transcription and induced secretion of IL-6 and plasminogen activator inhibitor
      (PAI-1). IL-6/PAI-1 expression and secretion were strongly inhibited by the
      tyrosine kinase inhibitor AG1478 and EGFR silencing. A significant reduction of
      EGF-stimulated IL-6/PAI-1 secretion was also obtained with the NFkB inhibitor
      dehydroxymethylepoxyquinomicin. Of 23 primary EOC tumors from advanced-stage
      patients with malignant ascites at surgery, 12 co-expressed membrane EGFR, IL-6
      and PAI-1 by immunohistochemistry; both IL-6 and PAI-1 were present in 83% of the
      corresponding ascites. Analysis of a publicly available gene-expression data set
      from 204 EOCs confirmed a significant correlation between IL-6 and PAI-1
      expression, and patients with the highest IL-6 and PAI-1 co-expression showed a
      significantly shorter progression-free survival time (P=0.028). This suggests
      that EGFR/NFkB/IL-6-PAI-1 may have a significant impact on the therapy of a
      particular subset of EOC, and that IL-6/PAI-1 co-expression may be a novel
      prognostic marker.

PMID- 22158047
TI  - microRNA-107 functions as a candidate tumor-suppressor gene in head and neck
      squamous cell carcinoma by downregulation of protein kinase CE.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer
      worldwide with about 600 000 new cases diagnosed each year. Understanding the
      molecular pathways that lead to HNSCC is crucial to identify new targets for anti
      cancer drug development. Protein kinase CE (PKCE) is elevated in HNSCC and
      regulates the activation of Akt, Stat3 and Rho GTPases. To date, the molecular
      mechanism of PKCE dysregulation in HNSCC remains to be elucidated. In silico
      analysis identified three putative microRNA-107 (miR-107) binding sites in the 3'
      untranslated region (UTR) of PKCE. An inverse relationship was revealed between
      miR-107 and PKCE in HNSCC cell lines. Delivery of miR-107 reduced PKCE levels in
      SCC15, SCC25 and CAL27, three HNSCC cell lines with high PKCE and low miR-107.
      The activity of a luciferase reporter construct containing the 3'-UTR of PKCE was
      downregulated by miR-107 and mutations in the three cognate miR-107 binding sites
      completely ablated the regulation by miR-107. Treatment with miR-107
      significantly blocked cell proliferation, DNA replication, colony formation and
      invasion in SCC25 and CAL27 cells. Ectopic expression of miR-resistant PKCE was
      sufficient to partially rescue the loss-of-function phenotype in miR-107
      overexpressing SCC25 cells. Tumor growth in nude mice was retarded by 93+/-7% in
      CAL27/miR-107 cells compared with CAL27/miR-control cells. Last, human primary
      HNSCC tumors with elevated PKCE had reduced miR-107 expression. Our results
      demonstrate that PKCE is directly regulated by miR-107 and, moreover, suggest
      that miR-107 may be a potential anti-cancer therapeutic for HNSCC.

PMID- 22158048
TI  - The 14q22.2 colorectal cancer variant rs4444235 shows cis-acting regulation of
      BMP4.
AB  - Common genetic variation at human 14q22.2 tagged by rs4444235 is significantly
      associated with colorectal cancer (CRC) risk. Re-sequencing was used to
      comprehensively annotate the 17kb region of strong linkage disequilibrium
      encompassing rs4444235. Through bioinformatic analyses using H3K4Me1, H3K4Me3,
      and DNase-I hypersensitivity chromatin signatures and evolutionary conservation
      we identified seven candidate disease-causing single-nucleotide polymorphisms
      mapping to six regions within the 17-kb region predicted to have regulatory
      potential. Reporter gene studies of these regions demonstrated that the element
      to which rs4444235 maps acts as an allele-specific transcriptional enhancer.
      Allele-specific expression studies in CRC cell lines heterozygous for rs4444235
      showed significantly increased expression of bone morphogenetic protein-4 (BMP4)
      associated with the risk allele (P<0.001). These data provide evidence for a
      functional basis for the non-coding risk variant rs4444235 at 14q22.2 and
      emphasizes the importance of genetic variation in the BMP pathway genes as
      determinants of CRC risk.

PMID- 22158049
TI  - Breaking the 'harmony' of TNF-alpha signaling for cancer treatment.
AB  - Tumor necrosis factor-alpha (TNF-alpha) binds to two distinct receptors,
      TNFR1/p55 and TNFR2/p75. TNF-alpha is implicated in the processes of tumor
      growth, survival, differentiation, invasion, metastases, secretion of cytokines
      and pro-angiogenic factors. We have shown that TNFR2/p75 signaling promotes
      ischemia-induced angiogenesis via modulation of several angiogenic growth
      factors. We hypothesized that TNFR2/p75 may promote tumor growth and
      angiogenesis. Growth of mouse Lewis lung carcinoma (LLC1) and/or mouse melanoma
      B16 cell was evaluated in wild type (WT), p75 knockout (KO) and double
      p55KO/p75KO mouse tumor xenograft models. Compared with WT and p55KO/p75KO mice,
      growth of tumors in p75KO mice was significantly decreased (twofold) in both LLC
      and B16 tumors. Tumor growth inhibition was correlated with decreases in vascular
      endothelial growth factor (VEGF) expression and capillary density, as well as
      bone marrow-derived endothelial progenitor cells incorporation into the
      functional capillary network, and an increase in apoptotic cells in LLC
      xenografts. Gene array analysis of tumor tissues showed a decrease in gene
      expression in pathways that promote tumor angiogenesis and cell survival.
      Blocking p75 by short-hairpin RNA in cultured LLCs led to increases in TNF
      mediated apoptosis, as well as decreases in the constitutive and TNF-mediated
      expression of angiogenic growth factors (VEGF, HGF, PLGF), and SDF-1alpha
      receptor CXCR4. In summary, p75 is essential for tumor angiogenesis and survival
      in highly vascularized murine lung tumor xenografts. Blocking p75 expression may
      lead to tumor regression. This may represent new and effective therapy against
      lung neoplasms and potentially tumors of other origin.

PMID- 22158050
TI  - MicroRNA-520/373 family functions as a tumor suppressor in estrogen receptor
      negative breast cancer by targeting NF-kappaB and TGF-beta signaling pathways.
AB  - MicroRNAs (miRNAs) as modulators of gene expression have been described to
      display both tumor-promoting and tumor-suppressive functions. Although their role
      has been studied in different tumor types, little is known about how they
      regulate nuclear factor kappaB (NF-kappaB) signaling in breast cancer. Here, we
      performed an unbiased whole genome miRNA (miRome) screen to identify novel
      modulators of NF-kappaB pathway in breast cancer. The screen identified 13 miRNA
      families whose members induced consistent effects on NF-kappaB activity. Among
      those, the miR-520/373 family inhibited NF-kappaB signaling through direct
      targeting of RELA and thus strongly reduced expression and secretion of the pro
      inflammatory cytokines interleukin (IL)-6 and IL-8. With a combination of in
      vitro and in vivo approaches, we propose a metastasis-suppressive role of miR
      520/373 family. miR-520c and miR-373 abrogated both in vitro cell invasion and in
      vivo intravasation of highly invasive MDA-MB-231 cells. However, knockdown of
      RELA did not affect their metastatic ability. mRNA profiling of MDA-MB-231 cells
      on overexpression of miR-520/373 members revealed a strong downregulation of
      transforming growth factor-beta (TGF-beta) signaling. Mechanistically, the
      metastasis-suppressive role of miR-520/373 can be attributed to direct
      suppression of TGFBR2, as the silencing of TGFBR2 phenocopied the effects of miR
      520/373 overexpression on suppression of Smad-dependent expression of the
      metastasis-promoting genes parathyroid hormone-related protein, plasminogen
      activator inhibitor-1 and angiopoietin-like 4 as well as tumor cell invasion, in
      vitro and in vivo. A negative correlation between miR-520c and TGFBR2 expression
      was observed in estrogen receptor negative (ER(-)) breast cancer patients but not
      in the ER positive (ER(+)) subtype. Remarkably, decreased expression of miR-520c
      correlated with lymph node metastasis specifically in ER(-) tumors. Taken
      together, our findings reveal that miR-520/373 family has a tumor-suppressive
      role in ER(-) breast cancer by acting as a link between the NF-kappaB and TGF
      beta pathways and may thus contribute to the interplay of tumor progression,
      metastasis and inflammation.

PMID- 22158051
TI  - Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin
      adherens junction and impairs NPC progression-associated properties.
AB  - Alpha B-crystallin (CRYAB) maps within the nasopharyngeal carcinoma (NPC) tumor
      suppressive critical region 11q22-23 and its downregulation is significantly
      associated with the progression of NPC. However, little is known about the
      functional impact of CRYAB on NPC progression. In this study we evaluated the NPC
      tumor-suppressive and progression-associated functions of CRYAB. Activation of
      CRYAB suppressed NPC tumor formation in nude mice. Overexpression of CRYAB
      affected NPC progression-associated phenotypes such as loss of cell adhesion,
      invasion, interaction with the tumor microenvironment, invasive protrusion
      formation in three dimensional Matrigel culture, as well as expression of
      epithelial-mesenchymal transition-associated markers. CRYAB mediates this ability
      to suppress cancer progression by inhibition of E-cadherin cytoplasmic
      internalization and maintenance of beta-catenin in the membrane that subsequently
      reduces the levels of expression of critical downstream targets such as cyclin-D1
      and c-myc. Both ectopically expressed and recombinant CRYAB proteins were
      associated with endogenous E-cadherin and beta-catenin, and, thus, the
      cadherin/catenin adherens junction. The CRYAB alpha-crystallin core domain is
      responsible for the interaction of CRYAB with both E-cadherin and beta-catenin.
      Taken together, these results indicate that CRYAB functions to suppress NPC
      progression by associating with the cadherin/catenin adherens junction and
      modulating the beta-catenin function.

PMID- 22158052
TI  - Blood cell origin of circulating microRNAs: a cautionary note for cancer
      biomarker studies.
AB  - Circulating, cell-free microRNAs (miRNAs) hold great promise as a new class of
      cancer biomarkers due to their surprisingly high stability in plasma, association
      with disease states, and ease of sensitive measurement. Yet little is known about
      the origin of circulating miRNAs in either healthy or sick people or what factors
      influence levels of circulating miRNA biomarkers. Of 79 solid tumor circulating
      miRNA biomarkers reported in the literature, we found that 58% (46 of 79) are
      highly expressed in one or more blood cell type. Plasma levels of miRNA
      biomarkers expressed by myeloid (e.g., miR-223, miR-197, miR-574-3p, and let-7a)
      and lymphoid (e.g., miR-150) blood cells tightly correlated with corresponding
      white blood cell counts. Plasma miRNA biomarkers expressed by red blood cells
      (e.g., miR-486-5p, miR-451, miR-92a, and miR-16) could not be correlated to red
      cell counts due to limited variation in hematocrit in the cohort studied but were
      significantly increased in hemolyzed specimens (20- to 30-fold plasma increase; P
      < 0.0000001). Finally, in a patient undergoing autologous hematopoietic cell
      transplantation, plasma levels of myeloid- and lymphoid-expressed miRNAs (miR-223
      and miR-150, respectively) tracked closely with changes in corresponding blood
      counts. We present evidence that blood cells are a major contributor to
      circulating miRNA and that perturbations in blood cell counts and hemolysis can
      alter plasma miRNA biomarker levels by up to 50-fold. Given that a majority of
      reported circulating miRNA cancer biomarkers are highly expressed in blood cells,
      we suggest caution in interpretation of such results as they may reflect a blood
      cell-based phenomenon rather than a cancer-specific origin.

PMID- 22158054
TI  - Distal tibial physeal bridge: a complication from a tension band plate and screw
      construct. Report of a case.
AB  - We report on a case of a tension band plate and screw construct (Eight Plate)
      used over the anterior distal tibia in an 9-year-old girl in an attempt to induce
      recurvatum of the ankle joint to correct a recalcitrant equinus deformity. With
      growth of the distal tibial physis, the epiphyseal screw was drawn through the
      physis into the distal tibial metaphysis, resulting in the creation of a
      transphyseal bony bar. Caution should be exercised when attempting temporary
      hemiepiphyseodesis using a plate and screw construct in small epiphyses or in an
      osteopenic bone.

PMID- 22158053
TI  - Cervical cancer prevention in low- and middle-income countries: feasible,
      affordable, essential.
AB  - The annual worldwide burden of the preventable disease cervical cancer is more
      than 530,000 new cases and 275,000 deaths, with the majority occurring in low-
      and middle-income countries (LMIC), where cervical cancer screening and early
      treatment are uncommon. Widely used in high-income countries, Pap smear (cytology
      based) screening is expensive and challenging for implementation in LMICs, where
      lower-cost, effective alternatives such as visual inspection with acetic acid
      (VIA) and rapid human papillomavirus (HPV)-based screening tests offer promise
      for scaling up prevention services. Integrating HPV screening with VIA in "screen
      and-treat-or-refer" programs offers the dual benefits of HPV screening to
      maximize detection and using VIA to triage for advanced lesions/cancer, as well
      as a pelvic exam to address other gynecologic issues. A major issue in LMICs is
      coinfection with human immunodeficiency virus (HIV) and HPV, which further
      increases the risk for cervical cancer and marks a population with perhaps the
      greatest need of cervical cancer prevention. Public-private partnerships to
      enhance the availability of cervical cancer prevention services within HIV/AIDS
      care delivery platforms through initiatives such as Pink Ribbon Red Ribbon
      present an historic opportunity to expand cervical cancer screening in LMICs.

PMID- 22158055
TI  - Treatment of an aneurysmal bone cyst of the lumbar spine in children and
      teenagers, about five cases.
AB  - The aneurysmal bone cyst is a rare tumor. Its treatment is complex when localized
      to the lumbar spine, with neurological, mechanical, and tumoral complications.
      The aim of this study is to describe these tumors, their treatment, and their
      long-term evolution, as well as to define an appropriate therapeutic strategy.
      Four of the five cysts had anterior and posterior extension. Three patients had
      neurological symptoms at diagnosis and two of them presented with pathological
      fracture. Surgical treatment was performed by intralesional resection. Long-term
      progress was always favorable, without recurrence or functional limitation. Two
      patients had a stable, mild spine deformity.

PMID- 22158056
TI  - NF-kappaB negatively impacts the myogenic potential of muscle-derived stem cells.
AB  - Inhibition of the inhibitor of kappa B kinase (IKK)/nuclear factor-kappa B (NF
      kappaB) pathway enhances muscle regeneration in injured and diseased skeletal
      muscle, but it is unclear exactly how this pathway contributes to the
      regeneration process. In this study, we examined the role of NF-kappaB in
      regulating the proliferation and differentiation of muscle-derived stem cells
      (MDSCs). MDSCs isolated from the skeletal muscles of p65(+/-) mice
      (haploinsufficient for the p65 subunit of NF-kappaB) had enhanced proliferation
      and myogenic differentiation compared to MDSCs isolated from wild-type (wt)
      littermates. In addition, selective pharmacological inhibition of IKKbeta, an
      upstream activator of NF-kappaB, enhanced wt MDSC differentiation into myotubes
      in vitro. The p65(+/-) MDSCs also displayed a higher muscle regeneration index
      than wt MDSCs following implantation into adult mice with muscular dystrophy.
      Additionally, using a muscle injury model, we observed that p65(+/-) MDSC
      engraftments were associated with reduced inflammation and necrosis. These
      results suggest that inhibition of the IKK/NF-kappaB pathway represents an
      effective approach to improve the myogenic regenerative potential of MDSCs and
      possibly other adult stem cell populations. Moreover, our results suggest that
      the improved muscle regeneration observed following inhibition of IKK/NF-kappaB,
      is mediated, at least in part, through enhanced stem cell proliferation and
      myogenic potential.

PMID- 22158057
TI  - A promoter polymorphism of neurotrophin 3 gene is associated with curve severity
      and bracing effectiveness in adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: A genetic association study to comprehensively investigate
      variations of neurotrophin 3 (NTF3) gene polymorphisms in a Chinese Han
      population. OBJECTIVE: To explore whether the NTF3 gene polymorphisms are
      associated with the susceptibility, curve severity, or bracing effectiveness of
      adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Scoliosis has
      developed in mice with NTF3 deficiency in previous studies. Increased expression
      of NTF3 mRNA was detected in the paravertebral muscle in AIS. Moreover, linkage
      study has defined a novel AIS locus on chromosome 12p while NTF3 gene is located
      exactly in this interval. All evidence indicates a potential role of NTF3 in the
      pathogenesis of AIS. As for brace treatment of AIS, continuous sensory
      stimulation caused by an orthosis could help awareness of body misalignment and
      trigger curve correction through postural reflex. While NTF3 gene is tightly
      associated with proprioceptive feedback mechanism to adjust postural control, we
      hypothesized NTF3 as a potential candidate gene associated with the bracing
      effectiveness. METHODS: A total of 362 AIS patients and 377 age-matched healthy
      controls were recruited. Two single-nucleotide polymorphisms (SNPs) were selected
      on the basis of the Chinese data from the HapMap project, and genotyping was
      carried out by polymerase chain reaction-restriction fragment length polymorphism
      for each SNP, respectively. Case-control study and case-only study were performed
      to define the contribution of NTF3 gene polymorphisms to predisposition and
      disease severity of AIS. Another subgroup of 120 skeletally immature AIS patients
      who received continuous brace treatment for minimal 2 years was genotyped, and
      bracing effectiveness was assessed to determine its association with NTF3 gene
      polymorphisms. RESULTS: The genotype and allele frequency distribution were
      similar between AIS and normal control for these 2 SNPs (chi2 test: P > 0.05).
      For SNP rs11063714 in the promoter region of NTF3 gene, AIS patients with AA
      genotype showed significantly lower mean maximum Cobb angle than the patients
      with AG or GG genotypes (analysis of variance: P = 0.008). In addition,
      skeletally immature bracing AIS patients with AA genotype possessed significantly
      higher successful ratio of brace treatment compared with GG genotype (chi2 test:
      P = 0.043). For SNP rs1805149, no significant association with predisposition or
      curve severity was detected. CONCLUSION: The NTF3 gene polymorphisms are not
      associated with the occurrence of AIS, but the promoter polymorphism (rs11063714)
      is associated with the curve severity, implicating an alleviating role of NTF3 in
      the curve progression of AIS. In addition, the promoter polymorphism is also
      associated with brace responsiveness. These findings indicated that NTF3 gene
      might be a disease-modifying gene of AIS.

PMID- 22158058
TI  - The unknown case:  part 1.

PMID- 22158059
TI  - Nonoperative treatment of lumbar spinal stenosis with neurogenic claudication: a
      systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To systematically review the evidence
      for the effectiveness of nonoperative treatment of lumbar spinal stenosis with
      neurogenic claudication. SUMMARY OF BACKGROUND DATA: Neurogenic claudication can
      significantly impact functional ability, quality of life, and independence in the
      elderly. METHODS.: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, and ICL
      databases up to January 2011 for randomized controlled trials published in
      English, in which at least 1 arm provided data on nonoperative treatments. Risk
      of bias in each study was independently assessed by 2 reviewers using 12
      criteria. Quality of the evidence was evaluated using Grades of Recommendations,
      Assessment, Development, and Evaluation (GRADE). RESULTS: From the 8635 citations
      screened, 56 were assessed and 21 trials with 1851 participants were selected.
      There is very low-quality evidence from 6 trials that calcitonin is no better
      than placebo or paracetamol, regardless of mode of administration or outcome.
      From single small trials, there is low-quality evidence that prostaglandins, and
      very low-quality evidence that gabapentin or methylcobalamin, improve walking
      distance. There is very low-quality evidence from a single trial that epidural
      steroid injections improve pain, function, and quality of life up to 2 weeks
      compared with home exercise or inpatient physical therapy. There is low-quality
      evidence from a single trial that exercise is of short-term benefit for leg pain
      and function compared with no treatment. There is low- and very low-quality
      evidence from 6 trials that multimodal nonoperative treatment is less effective
      than indirect or direct surgical decompression with or without fusion.
      CONCLUSION: Moderate- and high-GRADE evidence for nonoperative treatment is
      lacking and thus prohibiting recommendations to guide clinical practice. Given
      the expected exponential rise in the prevalence of lumbar spinal stenosis with
      neurogenic claudication, large high-quality trials are urgently needed.

PMID- 22158061
TI  - Cyclic tensile strain facilitates the ossification of ligamentum flavum through
      beta-catenin signaling pathway: in vitro analysis.
AB  - STUDY DESIGN: Histological, immunohistochemical, and real-time reverse
      transcription-polymerase chain reaction analyses of the expression of cell
      signaling and transcriptional factors in human ossification of ligamentum flavum
      (OLF). OBJECTIVE: To test the hypothesis that beta-catenin plays a role in the
      ossification of OLF cells in response to cyclic tensile strain. SUMMARY OF
      BACKGROUND DATA: Several studies have investigated the roles of biomechanical and
      metabolic factors in the development and progression of OLF, based on the
      importance of genetic and biological factors. The process of ossification
      includes enchondral ossification, although such pathology remains poorly defined.
      METHODS: Using real-time reverse transcription-polymerase chain reaction, we
      analyzed the mRNA expression levels of signaling factors known to be involved in
      the ossification process (beta-catenin, Runx2, Sox9, and osteopontin) in cultured
      OLF cells subjected to cyclic tensile strain. Cyclic tensile strain was produced
      by Flexercell FX-3000 (Flexercell International, Hillsborough, NC), applied for
      0, 6, 12, or 24 hours. The localization of these factors was examined in
      decalcified paraffin OLF sections by immunohistochemistry. Controlled samples
      were harvested from nonossified ligamentum flavum of patients who underwent
      thoracic posterior surgical procedures. RESULTS: Under resting conditions (no
      tensile strain), the mRNA levels of beta-catenin, Runx2, Sox9, and osteopontin in
      cultured OLF cells were significantly higher than in the control non-OLF cells.
      Application of cyclic tensile strain to OLF cells resulted in significant
      increases in mRNA expression levels of beta-catenin, Runx2, Sox9, and osteopontin
      at 24 hours. Hypertrophic chondrocytes present around the calcification front
      were immunopositive for Runx2 and osteopontin. Immunoreactivity of beta-catenin
      and Sox9 was strongly present in premature chondrocytes in the fibrocartilage
      area. CONCLUSION: Our results indicated that cyclic tensile strain applied to OLF
      cells activated their ossification through a process mediated by the beta-catenin
      signaling pathway.

PMID- 22158062
TI  - Prognostic factors for reduction of activities of daily living following
      osteoporotic vertebral fractures.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To elucidate the prognostic
      factors indicating reduced activities of daily living (ADL) at the time of the 6
      month follow-up after osteoporotic vertebral fracture (OVF). SUMMARY OF
      BACKGROUND DATA: OVF has severe effects on ADL and quality of life (QOL) in
      elderly patients and leads to long-term deteriorations in physical condition.
      Many patients recover ADL with acceleration of bony union and spinal stability,
      but some experience impaired ADL even months after fracture. Identifying factors
      predicting reduced ADL after OVF may prove valuable. METHODS: Subjects in this
      prospective study comprised 310 OVF patients from 25 institutes. All patients
      were treated conservatively without surgery. Pain, ADL, QOL, and other factors
      were evaluated on enrollment and at 6 months. ADL were evaluated using the
      criteria of the Japanese long-term care insurance system to evaluate the degree
      of independence. We defined reduced ADL as a reduction of at least single grade
      at 6 months after fracture and investigated factors predicting reduced ADL after
      OVF, using uni- and multivariate regression analysis. RESULTS: ADL were reduced
      at 6 months after OVF in 66 of 310 patients (21.3%). In univariate analysis, age
      more than 75 years (P = 0.044), female sex (P = 0.041), 2 or more previous spine
      fractures (P = 0.009), presence of middle column injury (P = 0.021), and lack of
      regular exercise before fracture (P = 0.001) were significantly associated with
      reduced ADL. In multivariate analysis, presence of middle column injury (odds
      ratio [OR], 2.26; P = 0.022) and lack of regular exercise before fracture (OR,
      2.49; P = 0.030) were significantly associated with reduced ADL. CONCLUSION:
      These results identified presence of middle column injury of the vertebral body
      and lack of regular exercise before fracture as prognostic factors for reduced
      ADL. With clarification and validation, these risk factors may provide crucial
      tools for determining subsequent OVF treatments. Patients showing these
      prognostic factors should be observed carefully and treated with more intensive
      treatment options.

PMID- 22158063
TI  - Biomechanical comparison of occiput-C1-C2 fixation techniques: C0-C1
      transarticular screw and direct occiput condyle screw.
AB  - STUDY DESIGN: In vitro human cadaveric biomechanical study. OBJECTIVE: The
      objective was to evaluate and compare the construct stability of occiput-C1-C2
      fixation provided by C0-C1 transarticular screws or occipital condyle screws.
      SUMMARY OF BACKGROUND DATA: The placement of an occipital plate is commonly
      recommended in occipitocervical fixation surgery. However, there are unique
      clinical situations in which the placement of the occipital plate may not be
      possible or may have already failed. For these situations, 2 novel techniques
      that use the occipital condyle have been recently introduced: (1) C0-C1
      transarticular screws fixation and (2) direct occipital condyle screws and C1
      lateral mass screws fixation. However, there is a lack of thorough biomechanics
      studies of these techniques. METHODS: Nondestructive kinematic tests and
      destructive tests were conducted in 16 fresh frozen cadaveric spines. As a
      nondestructive kinematic test, a pure moment of up to 2.0 N.m was applied in
      smooth continuous flexion/extension, lateral bending, and axial rotation motions.
      In addition to an intact-state case, a total of 5 different constructs (standard
      occipital plate, C0-C1 transarticular screws with/without occipital plate, and
      occipital condyle screws with/without occipital plate) were tested after
      destabilization of C0-C1 and C1-C2. All constructs had C2 pedicle screws
      fixation, and occipital condyle screws were incorporated with C1 lateral screws.
      RESULTS: All fixation techniques significantly reduced ranges of motion compared
      with the intact state. In comparison with the standard occipital plate construct,
      the 2 novel techniques showed higher stability in axial rotation and lower
      stability in lateral bending. In both nondestructive and destructive tests, there
      were no statistical differences between C0-C1 transarticular screw construct and
      occipital condyle screw construct. CONCLUSION: The C0-C1 transarticular screw
      technique and direct occipital condyle screw with C1 lateral mass screw technique
      can be salvage fixation methods when occipital plate fixation is not feasible.

PMID- 22158064
TI  - Association of heart rate with blood pressure variability: implications for blood
      pressure measurement.
AB  - BACKGROUND: Antihypertensive beta-blocker use is associated with greater
      intervisit blood pressure variability (BPV) and with less favorable outcomes
      compared to other antihypertensive agents. A theoretical model demonstrated that
      accuracy and precision of BP measurement are affected by heart rate (HR) at a
      constant cuff deflation rate. We aimed to examine the empirical relationship
      between HR and BPV in a clinical setting. METHODS: Intratracing variability in
      ambulatory BP monitoring (ABPM) were analyzed in search of a link between BPV and
      HR. BPV was expressed as standard deviation (s.d.), coefficient of variation
      (CV), and variability independent of the mean (VIM). RESULTS: In a dataset of
      4,693 subjects, HR was inversely associated with BPV and independently explained
      1.3% of between-subject variation in s.d. of awake systolic BP (1.5% of CV and
      VIM). Linear regression suggested 0.5 mm Hg increase in s.d. of systolic BP per
      10 beats per minute (bpm) decrease in HR. In a subset of 1,019 patients with
      available data on medications, HR was independently and inversely related with
      awake systolic BPV (P < 0.0001), more so in diuretic (P < 0.050) and renin
      angiotensin system antagonists-treated (P < 0.050) patients. Associations of beta
      blockade with increased BPV were abolished by model-adjustment for HR. In another
      subset of patients who were monitored twice (n = 635), HR had a mild (0.6%) but
      significant (P < 0.05) inverse contribution to the change in awake systolic BPV
      between repeated monitoring. CONCLUSIONS: Ambulatory BPV is inversely related to
      HR and is not increased in referred patients treated with beta-blockers after
      correction for HR.

PMID- 22158065
TI  - Plasma renin activity (PRA) levels and antihypertensive drug use in a large
      healthcare system.
AB  - BACKGROUND: Although hypertension guidelines have utility in treating
      uncomplicated hypertension, they often overlook the pathophysiologic basis and
      heterogeneity of hypertension. This may explain the relatively poor hypertension
      control rates. A proposed approach is to guide addition and subtraction of
      medications using ambulatory plasma renin activity (PRA) values. To evaluate the
      heterogeneity of hypertension and the medication burden associated with it, we
      investigated medication usage in relation to PRA among hypertensive patients
      within a large ethnically diverse organization. METHODS: A cross sectional data
      analysis was performed of hypertensive subjects with PRA measurements in the
      Kaiser Permanente Southern California database between 1 January 1998 and 31
      October 2009. RESULTS: Among 7,887 such patients 0, 1, 2, >=3 medication usage
      was 16%, 20%, 24%, 40% respectively. PRA levels ranged 1000-fold. Across PRA
      quartiles (Q1 to Q4) >=3 meds were prescribed to 50%, 40%, 34%, 37%. From low to
      high PRA quartiles there was no usage trend for angiotensin converting enzyme
      inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (71%), but diuretics
      increased (52%, 53%, 57%, 68%), calcium channel blocker's (CCB) fell (56%, 53%,
      51%, 42%), and beta-blockers fell (77%, 61%, 49%, 41%). Moreover, systolic BP
      fell (146, 142, 140, 135 mm Hg), blood urea nitrogen (BUN) rose (16, 17, 18, 20
      mg/dl), serum uric acid rose (6.1, 6.3, 6.5, 6.9 mg/dl), and chronic kidney
      disease rose (22%, 22%, 23%, 27%). CONCLUSIONS: Polytherapy was the norm for
      treating hypertension. Lower PRAs were associated with higher blood pressures and
      more medications. Higher PRAs were associated with lower pressures and fewer
      medications. The results indicate that opportunities exist to simplify
      antihypertensive therapy by using current ambulatory PRA levels to guide drug
      selections and subtractions.

PMID- 22158066
TI  - Sleep-time blood pressure as a therapeutic target for cardiovascular risk
      reduction in type 2 diabetes.
AB  - BACKGROUND: Independent studies have found that elevated sleep-time blood
      pressure (BP) is a better predictor of cardiovascular risk than the awake or 24-h
      BP means in patients without as well as with diabetes. However, the impact of the
      alteration over time of ambulatory BP on cardiovascular risk has never been
      investigated. We evaluated in a subgroup cohort of MAPEC (Monitorizacion
      Ambulatoria para Prediccion de Eventos Cardiovasculares, i.e., ambulatory blood
      pressure monitoring for prediction of cardiovascular events) with diabetes
      whether reduced cardiovascular risk is more related to the progressive decrease
      of awake vs. asleep BP. METHODS: We studied 607 patients with type 2 diabetes
      during a median 5.4 years follow-up. Those with hypertension at baseline (74%)
      were randomized to ingest all their prescribed hypertension medications upon
      awakening or >=1 of them at bedtime. BP was measured for 48 h at baseline, and
      again annually in all patients, or more frequently (quarterly) after adjustments
      in treatment. RESULTS: Using baseline data, when asleep BP was adjusted by awake
      mean, only the former was a significant predictor of outcome in a Cox
      proportional-hazard model adjusted for sex, age, anemia, and chronic kidney
      disease. Analyses of changes in BP during follow-up revealed a 20% cardiovascular
      risk reduction for each 5 mm Hg decrease in asleep systolic BP mean (P < 0.001),
      independently of changes in clinic or any other ambulatory BP parameter.
      CONCLUSIONS: Sleep-time BP is the most significant independent prognostic marker
      of cardiovascular events in diabetes. Most important, decreasing sleep-time BP, a
      novel therapeutic target requiring proper patient evaluation by ambulatory
      monitoring, was the most significant independent predictor of event-free survival
      in diabetes.

PMID- 22158067
TI  - Switching from high-fat to low-fat diet normalizes glucose metabolism and
      improves glucose-stimulated insulin secretion and insulin sensitivity but not
      body weight in C57BL/6J mice.
AB  - OBJECTIVES: Environmental factors such as a high-fat diet contribute to type 2
      diabetes and obesity. This study examined glycemia, insulin sensitivity, and beta
      cell function after switching from a high-fat diet to a low-fat diet in mice.
      METHODS: C57BL/6J mice were fed a high-fat diet or low-fat diet for 18 months,
      after which mice on the high-fat diet either maintained this diet or switched to
      a low-fat diet for 4 weeks. Body weight and glucose and insulin responses to
      intraperitoneal glucose were determined. Insulin secretion (insulinogenic index:
      the 10-minute insulin response divided by the 10-minute glucose level) and
      insulin sensitivity (1 divided by basal insulin) were determined. RESULTS: After
      18 months on a high-fat diet, mice had glucose intolerance, marked
      hyperinsulinemia, and increased body weight compared to mice on a low-fat diet (P
      < 0.001). Switching from a high-fat diet to low-fat diet normalized glucose
      tolerance, reduced but not normalized body weight (P < 0.001), increased insulin
      secretion (248 +/- 39 vs 141 +/- 46 pmol/mmol; P = 0.028) and improved but not
      normalized insulin sensitivity (3.2 +/- 0.1 vs 1.0 +/- 0.1 [pmol/L]; P = 0.012).
      CONCLUSION: Switching from a high-fat diet to low-fat diet normalizes glucose
      tolerance and improves but not normalizes insulin secretion and insulin
      sensitivity. These effects are more pronounced than the reduced body weight.

PMID- 22158068
TI  - Pancreatoduodenectomy following neoadjuvant chemoradiation therapy in uncinate
      process pancreatic cancer.
AB  - OBJECTIVE: The objective of the study was to delineate surgical outcomes of
      pancreatoduodenectomy following neoadjuvant concurrent chemoradiation therapy
      (CCRT) in uncinate process pancreatic cancer (UPC). METHODS: We reviewed 97
      patients with resected usual pancreatic head cancer (PHC) and UPC and analyzed
      clinicopathologic characteristics and survival outcomes of PHC and UPC with a
      review of the reported literature regarding UPC. RESULTS: Twenty-five patients
      (27.8%) had UPC, and 72 patients had PHC. Pylorus-preserving
      pancreatoduodenectomy was performed in 67 patients (69.1%) and conventional
      pancreatoduodenectomy in 28 patients (28.9%), and 2 patients needed total
      pancreatectomies. When comparing UPCs with PHCs, less frequent jaundice (P =
      0.009) and more advanced stages of cancers at the time of diagnosis (linear-to
      linear association, P = 0.03) were found in UPCs, and CCRT was administered more
      frequently in UPCs (P = 0.013). Survival outcomes between PHC and UPC were
      similar, with median survival rates of 25.9 and 30.5 months, respectively (P =
      0.702). In addition, disease-free survival was similar between the 2 groups (15.6
      and 15.2 months, respectively; P = 0.4503). Our oncologic outcome of
      pancreatectomy for UPC is likely to be more acceptable compared with those
      previously reported in the literature. CONCLUSIONS: Although UPCs are found in
      relatively advanced clinical stages, favorable oncologic outcomes may be obtained
      by pancreatectomy following preoperative CCRT.

PMID- 22158069
TI  - Long-term follow-up of nutritional status, pancreatic function, and morphological
      changes of the pancreatic remnant after pancreatic tumor resection in children.
AB  - OBJECTIVES: The objectives of the present study were to determine nutritional
      status, pancreatic function, and morphological changes of the pancreatic remnant
      after pancreatic tumor resection in children. METHODS: The nutritional status was
      evaluated by the patterns of growth. Pancreatic function was evaluated by using a
      questionnaire, the Bristol stool form chart, the serum levels of fasting blood
      glucose, and hemoglobin A1c (HbA1c). Morphological changes of the pancreatic
      remnant were evaluated by computed tomography, magnetic resonance image, or
      magnetic resonance cholangiopancreatography. RESULTS: The present study consisted
      of 6 patients with pancreatic tumor (5 solid pseudopapillary tumors of the
      pancreas and 1 pancreatoblastoma) who underwent the following operations: tumor
      enucleation (3), distal pancreatectomy with splenectomy (1), and pylorus
      preserving pancreatoduodenectomy (PPPD [2]). The serum levels of HbA1c have been
      gradually elevated in 2 patients with PPPD. A significant decrease in pancreatic
      parenchymal thickness and dilatation of the main pancreatic duct were observed in
      2 patients with PPPD. CONCLUSION: Endocrine pancreatic insufficiency after PPPD
      may be explainable by obstructive pancreatitis after operation. Taking together
      the results of pancreatic endocrine function and morphological changes of
      pancreatic remnant after PPPD, tumor enucleation should be considered as surgical
      approach in children with pancreas head tumor whenever possible.

PMID- 22158070
TI  - Detection of baicalin metabolites baicalein and oroxylin-a in mouse pancreas and
      pancreatic xenografts.
AB  - OBJECTIVES: Scutellaria baicalensis has been a subject of research interest due
      to its potential multiple therapeutic benefits. This study was to examine the
      distribution of baicalein, wogonin, oroxylin A and their glucuronide/sulfate
      conjugated metabolites in plasma, colon, small intestine, lung, liver, pancreas,
      kidney, and prostate tissues and in pancreatic tumor in a xenograft animal model.
      In addition, we examined metabolic stability of baicalin in these tissues.
      METHODS: A mouse xenograft model was prepared by injection of 3 * 10 human
      pancreatic cancer MiaPaCa-2 cells subcutaneously into nude mice. Mice were
      randomly allocated to control diet (AIN-76A) and 1% S. baicalensis diet (n = 8
      per group) for 13 weeks. Levels of baicalein, wogonin, oroxylin A, and their
      conjugates in mouse tissues were measured by high-pressure liquid chromatography
      after enzymatic hydrolysis and then extraction. RESULTS: A substantial amount of
      baicalin (34%-63%) was methylated to oroxylin A and its conjugates in various
      organs during absorption. Whereas plasma contained predominantly conjugates of
      baicalein, wogonin, and oroxylin A, both aglycones and conjugates were found in
      all other tissues investigated and in tumor. CONCLUSIONS: Substantial
      accumulation of bioactive metabolites are found in target tissues, suggesting
      strong potential for S. baicalensis use as a preventive or adjuvant supplement
      for pancreatic cancer.

PMID- 22158072
TI  - Circulating CD4+CD25+ regulatory T cells in patients with pancreatic cancer.
AB  - OBJECTIVES: Regulatory T cells (Treg) can inhibit immune responses mediated by T
      cells. The aim of this study was to evaluate the prevalence of Treg in peripheral
      blood mononuclear cells from patients with pancreatic cancers in relation to
      their clinical outcomes. METHODS: Among a total of 100 patients with ductal
      adenocarcinoma of the pancreas, 40 underwent pancreatectomy and 60 had
      unresectable disease. Their peripheral blood mononuclear cells were evaluated to
      determine the proportion of CD4CD25 (FoxP3) T cells, as a percentage of the total
      CD4 cells, by flow cytometric analysis. RESULTS: The percentage of Treg in the
      patients with pancreatic cancer was significantly lower than that in the healthy
      volunteers (P = 0.048), and the patients who underwent surgical resection had
      lower Treg levels than those with unresectable disease (P = 0.040). Patients in
      the resected group with a higher percentage of Treg survived longer (P = 0.021).
      Treg in patients who remained disease free at postoperative 12 months
      significantly decreased compared to that of the postoperative period (P = 0.009).
      CONCLUSION: A relative increase in Treg may be related to immunosuppression and
      tumor progression in patients with pancreatic cancer. The immunological
      monitoring of Treg may be useful to predict the prognosis for patients with
      pancreatic cancer.

PMID- 22158071
TI  - Inhibition of glycogen phosphorylation induces changes in cellular proteome and
      signaling pathways in MIA pancreatic cancer cells.
AB  - OBJECTIVES: Novel quantitative proteomic approaches were used to study the
      effects of inhibition of glycogen phosphorylase on proteome and signaling
      pathways in MIA PaCa-2 pancreatic cancer cells. METHODS: We performed
      quantitative proteomic analysis in MIA PaCa-2 cancer cells treated with a
      stratified dose of CP-320626 (5-chloro-1H-indole-2-carboxylic acid [1-(4
      fuorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2 oxoethyl] amide) (25, 50, and 100
      MUM). The effect of metabolic inhibition on cellular protein turnover dynamics
      was also studied using the modified SILAC (stable isotope labeling with amino
      acids in cell culture) method. RESULTS: A total of 22 protein spots and 4
      phosphoprotein spots were quantitatively analyzed. We found that dynamic
      expression of total proteins and phosphoproteins was significantly changed in MIA
      PaCa-2 cells treated with an incremental dose of CP-320626. Functional analyses
      suggested that most of the proteins differentially expressed were in the pathways
      of mitogen-activated protein kinase/extracellular signal-regulated kinase and
      tumor necrosis factor alpha/nuclear factor kappaB. CONCLUSIONS: Signaling
      pathways and metabolic pathways share many common cofactors and substrates
      forming an extended metabolic network. The restriction of substrate through 1
      pathway such as inhibition of glycogen phosphorylation induces pervasive
      metabolomic and proteomic changes manifested in protein synthesis, breakdown, and
      posttranslational modification of signaling molecules. Our results suggest that
      quantitative proteomic is an important approach to understand the interaction
      between metabolism and signaling pathways.

PMID- 22158073
TI  - Pancreas size and volume on computed tomography in normal adults.
AB  - OBJECTIVE: The objective of the study was to evaluate quantitatively normal
      pancreatic morphology, size, and volume stratified by age and sex. METHODS:
      Adults without known pancreatic disease underwent computed tomography (n = 249)
      were evaluated by linear pancreatic dimensions, volume determinations (summation
      of areas), and histograms. A subset was reread to evaluate interreader
      reliability. Ordinary least squares regression was used to model the average of
      each measurement as a function of sex and age. RESULTS: Although increasing age
      was associated with a moderate decrease in pancreatic volume and in the size of
      the body and tail, the anteroposterior diameter of the head increased with age up
      to 71 years. Measurements of the head and total volume were smaller among women,
      but the body and tail showed no sex difference. Across all measurements,
      differences due to sex and age were smaller in magnitude than the random
      variation between subjects. Despite adhering to a detailed protocol, we observed
      both systematic and random differences between readers in performing the
      measurements. CONCLUSIONS: Although size and volume of the normal pancreas in
      adults measured with multislice computed tomography are smaller among women and
      those who are older, the anteroposterior diameter of the head increases slightly
      throughout the majority of the age range.

PMID- 22158074
TI  - Serum HSP70: a novel biomarker for early detection of pancreatic cancer.
AB  - OBJECTIVES: Heat shock protein 70 (HSP70) is overexpressed in human pancreatic
      cancer cell lines. To determine if serum HSP70 levels are elevated in patients
      with pancreatic cancer and can function as a biomarker for early detection of
      pancreatic cancer. METHODS: Study subjects were divided into 3 groups:
      histologically proven pancreatic cancer (PC; n = 23), chronic pancreatitis (CP; n
      = 12), and matched normal control subjects (C; n = 10). Serum HSP70 levels were
      determined using a novel immunoelectrophoresis method developed and validated by
      the authors. Significance of difference between the groups was analyzed with
      analysis of variance (ANOVA). Receiver operating characteristic (ROC) curve
      analysis was performed to discriminate patients with pancreatic cancer from
      normal controls. RESULTS: The mean +/- SE serum HSP70 levels in the PC, CP, and C
      groups were 1.68 +/- 0.083 ng/mL, 0.40 +/- 0.057 ng/mL, and 0.04 ng/mL,
      respectively. Serum HSP70 levels in the PC group were significantly higher
      compared with either the CP or C groups (P < 0.01). The sensitivity and
      specificity of elevated serum HSP70 in the PC group was 74% and 90%,
      respectively. CONCLUSIONS: Serum HSP70 levels are significantly increased in
      patients with pancreatic cancer and may be useful as an additional biomarker for
      the detection of pancreatic cancer.

PMID- 22158075
TI  - Biological and prognostic relevance of mitogen-activated protein kinases in
      pancreatic adenocarcinoma.
AB  - OBJECTIVES: The aims of this study were to study the biological and clinical
      significance of 3 main proteins of the mitogen-activated protein kinase (MAPK)
      signaling pathway, ERK1/2, P38, and MKK4, in a series of patients having
      pancreatic adenocarcinomas treated by surgery. METHODS: We examined the
      immunohistochemical expression of 3 MAPK proteins, ERK1/2, P38, and MKK4 in 99
      surgically resected pancreatic ductal adenocarcinomas. Tumor protein expression
      was studied with regard to pathological characteristics and to postsurgical
      recurrence-free and overall survivals. RESULTS: MKK4 expression was related to
      tumor cell proliferation, evaluated by the Ki67 index (P < 0.01). ERK1/2
      expression was related to a shorter recurrence-free survival on both univariate
      and multivariate analysis (P < 0.01; odds ratio, 8.39; 95% confidence interval,
      2.68-26.26) independently of lymph node metastases and tumor size, and to a
      shorter overall survival (P = 0.01) on univariate analysis. In patients without
      postsurgical treatment, both ERK1/2 and P38 tumor expression correlated with a
      shorter recurrence-free survival (P < 0.01 and P = 0.02, respectively).
      CONCLUSIONS: The results of our study suggest that in pancreatic ductal
      adenocarcinomas, the MKK4 protein was directly related to high cell
      proliferation, and that tumor ERK1/2 and P38 expression correlated to shorter
      postsurgical recurrence-free and overall survivals.

PMID- 22158076
TI  - Cyclosporin a, but not FK506, induces osmotic lysis of pancreas zymogen granules,
      intra-acinar enzyme release, and lysosome instability by activating K+ channel.
AB  - OBJECTIVES: The immunosuppressant tacrolimus (FK506) has improved pancreas
      allograft survival compared with cyclosporin A (CsA), possibly because of reduced
      acute pancreatitis following ischemia-reperfusion injury. Ion permeabilities in
      zymogen granule (ZG) membranes, including a KCNQ1 K channel, promote hormone
      stimulated enzyme secretion. We investigated whether a differential modulation of
      ZG and lysosomal ion permeabilities and enzyme secretion by CsA/FK506 contributes
      to pancreatitis. METHODS: Rat ZGs and lysosomes were isolated by gradient
      centrifugation, ion permeabilities assayed by osmotic lysis, and single-channel
      currents recorded in a planar lipid bilayer. Amylase release was measured in
      permeabilized acini and lysosomal cathepsin B release detected by immunoblotting.
      RESULTS: CsA (1-10 MUM), but not FK506, enhanced ZGs osmotic lysis by selectively
      increasing K permeability up to 5-fold. Zymogen granule membrane K channels
      showed ~2-fold increased single-channel open probability with CsA only.
      Cyclosporin A selectively increased basal (~2-fold), but not cholecystokinin
      octapeptide (1 nM)-induced amylase secretion in K medium only. Cyclosporin A (5
      MUM), but not FK506, increased cathepsin B release from lysosomes. CONCLUSIONS:
      Cyclosporin A selectively opens the ZG K channel and induces cathepsin B release
      from lysosomes, which cause increased in situ lysis of ZGs and may aggravate or
      fuel acute allograft pancreatitis following hypoxia-reperfusion injury.

PMID- 22158077
TI  - Susceptibility of human pancreatic beta cells for cytomegalovirus infection and
      the effects on cellular immunogenicity.
AB  - OBJECTIVES: Human cytomegalovirus (HCMV) infection has been suggested to be a
      causal factor in the development of type 1 diabetes, posttransplantation
      diabetes, and the failure of islet allografts. This effect of CMV has been
      interpreted as an indirect effect on the immune system rather than direct
      infection-induced cell death. In the present study, we investigated (i) the
      susceptibility of beta cells to HCMV infection, (ii) regulation of immune cell
      activating ligands, (iii) release of proinflammatory cytokines, and (iv) the
      effects on peripheral blood mononuclear cell (PBMC) activation. METHODS: CM
      insulinoma cells and primary beta cells were HCMV-infected in vitro using a
      laboratory and a clinical HCMV strain. The susceptibility to infection was
      measured by the expression of viral genes and proteins. Furthermore, expression
      levels of Major Histocompatibility Complex I, Intracellular Adhesion Molecule-1,
      and Lymphocyte Function Associated Antigen-3 and the release of proinflammatory
      cytokines were determined. In addition, PBMC activation to HCMV-infected beta
      cells was determined. RESULTS: beta Cells were susceptible to HCMV infection.
      Moreover, the infection increased the cellular immunogenicity, as demonstrated by
      an increased MHC I and ICAM-1 expression and an increased proinflammatory
      cytokine release. Human cytomegalovirus-infected CM cells potently activated
      PBMCs. The infection-induced effects were dependent on both viral "sensing" and
      viral replication. CONCLUSIONS: In vivo beta-cell HCMV infection and infection
      enhanced cellular immunogenicity may have important consequences for native or
      transplanted beta-cell survival.

PMID- 22158080
TI  - Hypertension in 2011: New insights--from risk factors to treatment implications.
AB  - The results of several hypertension studies published in 2011 have contributed to
      our knowledge on the risks of and treatment for this condition, including the
      effects of slow-wave sleep, nocturnal dosing of medication, variability in post
      stroke blood-pressure reduction, and the impacts of a low-sodium diet.

PMID- 22158081
TI  - Anticoagulation therapy: Idrabiotaparinux noninferior to warfarin for long-term
      treatment of pulmonary embolism.

PMID- 22158083
TI  - Fabrication of biologically derived injectable materials for myocardial tissue
      engineering.
AB  - This protocol provides methods for the preparation of an injectable extracellular
      matrix (ECM) gel for myocardial tissue engineering applications.  Briefly,
      decellularized tissue is lyophilized, milled, enzymatically digested, and then
      brought to physiological pH.  The lyophilization removes all water content from
      the tissue, resulting in dry ECM that can be ground into a fine powder with a
      small mill.  After milling, the ECM powder is digested with pepsin to form an
      injectable matrix. After adjustment to pH 7.4, the liquid matrix material can be
      injected into the myocardium.  Results of previous characterization assays have
      shown that matrix gels produced from decellularized pericardial and myocardial
      tissue retain native ECM components, including diverse proteins, peptides and
      glycosaminoglycans.  Given the use of this material for tissue engineering, in
      vivo characterization is especially useful; here, a method for performing an
      intramural injection into the left ventricular (LV) free wall is presented as a
      means of analyzing the host response to the matrix gel in a small animal model. 
      Access to the chest cavity is gained through the diaphragm and the injection is
      made slightly above the apex in the LV free wall.  The biologically derived
      scaffold can be visualized by biotin-labeling before injection and then staining
      tissue sections with a horse radish peroxidase-conjugated neutravidin and
      visualizing via diaminobenzidine (DAB) staining.  Analysis of the injection
      region can also be done with histological and immunohistochemical staining.  In
      this way, the previously examined pericardial and myocardial matrix gels were
      shown to form fibrous, porous networks and promote vessel formation within the
      injection region.

PMID- 22158084
TI  - Urinary vitamin D-binding protein is elevated in patients with endometriosis.
AB  - BACKGROUND: Recently, proteomic technologies have demonstrated that several
      proteins are differently expressed in various body fluids of patients with
      endometriosis compared with those without this condition. The aim of this study
      was to investigate proteins secreted in urine of patients with endometriosis
      using proteomic techniques in order to identify potential markers for the
      clinical diagnosis of endometriosis. METHODS: Urine samples were collected from
      women undergoing laparoscopy for different indications including pelvic masses,
      pelvic pain, suspicious endometriosis, infertility and diagnostic evaluation.
      Proteomic techniques and mass spectrometry were used to identify proteins
      secreted in the urine of the patients with and without endometriosis and
      quantification of identified protein was performed using western blot and
      specific commercial sandwich enzyme-linked immunosorbent assays (ELISA). RESULTS:
      Twenty-two protein spots were differentially expressed in the urine of patients
      with and without endometriosis, one of which was identified as urinary vitamin D
      binding protein (VDBP). ELISA quantification of urinary VDBP corrected for
      creatinine expression (VDBP-Cr) revealed that urinary VDBP-Cr was significantly
      greater in patients with endometriosis than in those without (111.96 +/- 74.59
      versus 69.90 +/- 43.76 ng/mg Cr, P = 0.001). VDBP-Cr had limited value as a
      diagnostic marker for endometriosis (Sensitivity 58%, Specificity 76%). When
      combined with serum CA-125 levels (the product of serum CA-125 and urinary VDBP
      Cr), it did not significantly increase the diagnostic power of serum CA-125
      alone. CONCLUSIONS: Urinary VDBP levels are elevated in patients with
      endometriosis. They have limited value as a potential diagnostic biomarker for
      endometriosis but suggest it would be worthwhile to investigate other urinary
      proteins for this purpose.

PMID- 22158085
TI  - Identification and validation of novel serum markers for early diagnosis of
      endometriosis.
AB  - BACKGROUND: Non-invasive diagnosis of endometriosis is urgently required to
      prevent the long delay between the onset of symptoms and diagnosis. A biomarker
      that possesses both high sensitivity and specificity is greatly required. Here,
      we describe the use of a proteomic approach to identify potential novel
      endometrial antigens using sera from endometriosis patients and healthy controls,
      with evaluation of biomarkers for non-invasive diagnosis of endometriosis.
      METHODS: A cross-sectional study was conducted to identify specific endometrial
      antigens using 1D and 2D western blots in women with early endometriosis (n =
      17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five
      immunoreactive spots were analyzed using matrix-assisted laser
      desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis.
      ELISAs were established for specific epitopes and autoantibody titres were
      estimated in an independent cohort comprising women with early endometriosis (n =
      18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for
      validation. RESULTS: The 2D western blot analysis resulted in the identification
      of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2
      (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the
      epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were
      significantly elevated in endometriosis patients when compared with controls.
      Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c
      autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%),
      anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c
      autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of
      serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis.
      CONCLUSIONS: Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti
      SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti
      TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.

PMID- 22158086
TI  - Combined transanal and laparoscopic approach for the treatment of deep
      endometriosis infiltrating the rectum.
AB  - BACKGROUND: Two surgical approaches are employed in the treatment of deep
      infiltrating endometriosis of the rectum (DIER): colorectal resection and nodule
      excision. In 2009, we introduced a new technique for transanal full thickness
      disc excision of endometriotic nodules infiltrating the low and middle rectum,
      using the Contour(r) TranstarTM stapler (Ethicon Endo-Surgery inc., Cincinnati,
      OH, USA). The aim of this retrospective study was to describe the technique and
      to present data on the feasibility of this technique. METHODS: From April 2009 to
      October 2010, all patients presenting with DIER and undergoing full thickness
      excision using the Contour(r) TranstarTM stapler were enrolled in the study. Pre
      , intra- and post-operative data were collected and reported. RESULTS: Six
      nulliparous women were managed using this technique during the study period. The
      rectal wall discs removed measured from 40 * 45 to 60 * 50 mm. In two cases,
      microscopic foci were noted on one of the margins but in four cases the limits
      were clear. Operating time varied from 180 to 450 min. Four women were completely
      free of post-operative digestive complaints. CONCLUSIONS: Despite the small
      numbers in this series, our data suggest that the new technique of transanal
      rectal disc excision using the contour stapler may be applied in patients with
      infiltrating endometrial nodules of the rectum up to 10 cm from the anal margin
      and up to 5 cm in diameter. This new procedure promises to be a useful addition
      to the surgeon's armamentarium in a multidisciplinary approach to deep pelvic
      endometriosis.

PMID- 22158087
TI  - HSFY genes and the P4 palindrome in the AZFb interval of the human Y chromosome
      are not required for spermatocyte maturation.
AB  - BACKGROUND: Recurrent AZFb deletions on the human Y chromosome are associated
      with an absence of ejaculated spermatozoa consequent to a meiotic maturation
      arrest that prevents the progression of germ cells to haploid stages. The extreme
      rarity of partial deletions has hampered the identification of the AZFb genes
      required for normal meiotic stages. The critical interval, refined by two
      overlapping deletions associated with full spermatogenesis (AZFc and b1/b3),
      measures over 4 Mb and contains 13 coding genes: CDY2, XKRY, HSFY1, HSFY2,
      CYORF15A, CYORF15B, KDM5D, EIF1AY, RPS4Y2 and four copies of RBMY. METHODS AND
      RESULTS: We screened 1186 men from infertile couples for Y chromosome deletions,
      and identified three unrelated oligozoospermic men and one azoospermic man who
      carry an identical 768 kb deletion resulting in loss of the entire P4 palindrome,
      including both HSFY genes, the only coding genes within the deletion interval.
      This 768 kb deletion was not found in 1179 control men. The deletion breakpoints
      share only 4 bp of nucleotide identity, revealing that the deletions are not
      recurrent, but are descendants of a founding deletion. Confirming this, we find
      that all four men carry a Y chromosome of the same highly defined haplogroup
      (R1b1b1a1b) (incidence 30% in Southern France), although further haplotype
      analyses showed that they were not closely related. CONCLUSIONS: Although the
      HSFY deletion is restricted to our infertile group, it has been transmitted
      naturally over many generations, indicating that HSFY genes make only a slight
      contribution to male fertility. Importantly, our study formally excludes HSFY
      genes as the AZFb factor required for progression through meiosis.

PMID- 22158089
TI  - An observational study on the perceptive and physiological variables during a
      10,000-m race walking competition.
AB  - In this study, we observed the variations on physiological and perceptual
      variables during a self-paced 10,000-m race walking (RW) event with the aim to
      trace a preliminary performance profile of the distance. In 14 male athletes, the
      heart rate (HR) was monitored continuously throughout the event. The rating of
      perceived exertion (RPE) was collected using the Borg's 6-20 RPE scale placed at
      each 1,000 m of an outdoor tartan track. Pacing data were retrieved from the
      official race results and presented as percent change compared with the first
      split time. The athletes spent 95.4% at 90-100% of the HRpeak, whereas the other
      work (4.6%) was negligible. During the race, a shift toward higher HR values was
      observed because % HRpeak increased by 3.6% in the last vs. the first 1,000-m
      sector (p = 0.002, effect size [ES] = 1.55 +/- 0.68, large). The mean RPE
      reported by the athletes in the last 1,000 m was significantly higher than in the
      first 5 sectors (p < 0.02, ES = 1.93-2.96, large to very large). The mean percent
      change increased between the first 6 sectors and the last 1,000-m sector (p <
      0.01, ES = 1.02-2.1, moderate to very large). The analysis of walking velocity at
      each 1,000-m sector suggested the adoption of a negative pacing. In conclusion,
      the RPE may be a valid marker of exercise intensity even in real settings. Match
      physiological and perceptual data with work rate are required to understand race
      related regulatory processes. Pacing should be considered as a conscious behavior
      decided by the athletes based on the internal feedback during the race.

PMID- 22158090
TI  - Workload comparison between hiking and indoor physical activity.
AB  - Walking is a physical activity able to maintain and improve aerobic fitness. This
      activity can easily be performed in all seasons both outdoors and indoors, but
      when it is performed in its natural environment, the use of specific equipment is
      required. In particular, it has been demonstrated that the use of trekking boots
      (TBs) induces a larger workload than those used indoors. Because an adequate
      fitness level is needed to practice hiking in safety, it is useful to know the
      energy demand of such an activity. This research aims at defining the metabolic
      engagement of hiking on natural paths with specific equipment at several speeds
      and comparing this with indoor ones (on a treadmill). This can thence be used to
      define the load that better reflects the one required to walk on natural paths.
      The walking energy cost (joules per kilogram per meter) at several speeds (0.28,
      0.56, 0.84, 1.11, and 1.39 m.s(-1))-on level natural terrain while wearing
      suitable footwear (TBs) and on a treadmill at various raising slopes (0, 1, 2, 3,
      4%) while wearing running shoes-was measured in 14 healthy young men (age 23.9 +/
      2.9 years, stature 1.75 +/- 0.04 m, and body mass 72.9 +/- 6.3 kg). A
      physiological evaluation of all the subjects was performed before energy cost
      measurements. The results showed that outdoors, the oxygen uptake was
      consistently less than the ventilatory threshold at all speeds tested and that a
      3% slope on the treadmill best reflects the outdoor walking energy expenditure.
      These findings will prove useful to plan proper training for hiking activity or
      mixed (outdoors and indoors) training program.

PMID- 22158091
TI  - Validation of a nonexercise prediction equation of anaerobic power.
AB  - This study examined the validity of estimating anaerobic power in college-aged
      students using anthropometric data and a paper and pencil test. Peak power (PP)
      and mean power (MP) were determined for 157 subjects (92 men and 65 women) using
      a standard Wingate anaerobic test (WAnT) at a resistance of 0.075 and 0.10
      kg.body mass for women and men, respectively. Subjects completed previously
      established paper and pencil tests for assessing aerobic capacity and rated their
      ability to perform tasks related to anaerobic power, such as their vertical jump
      height relative to peers. Descriptive statistics were generated, and multiple
      regression was performed using SAS v9.1 to assess the ability of paper and pencil
      tests to predict PP and MP from the WAnT. Mean (+/-SD) age, height, body mass,
      body mass index, PP, and MP for subjects were 22.1 +/- 2.5 years, 175.6 +/- 7.5
      cm, 78.5 +/- 11.4 kg, 25.4 +/- 3.0 kg.m, 1015.2 +/- 169.7 W, and 784.5 +/- 122.1
      W and 22.0 +/- 3.0 years, 163.6 +/- 7.4 cm, 61.1 +/- 10.4 kg, 22.8 +/- 3.4 kg.m,
      593.0 +/- 102.4 W, and 478.8 +/- 72.8 W, respectively. Mean estimated jump height
      (EJHt) rating values were 5.8 +/- 1.5 and 4.7 +/- 1.5 (on a 1-9 Likert-type
      scale) for men and women, respectively. The following multiple regression models
      were developed:PP = -34.5 + 249.6 (gender; female = 0, male = 1) + 8.1 (BMkg) +
      27.8 (EJHt) (R = 0.82, SEE = 106.6 W);MP = -37.7 + 163.7 (gender) + 6.7 (BMkg) +
      22.8 (EJHt) (R = 0.87, SEE = 65.5 W).It was concluded that valid estimates for PP
      and MP could be obtained from anthropometric data and a single question paper and
      pencil test asking subjects to estimate relative jumping ability, without the
      need for performing the Wingate anaerobic cycle test.

PMID- 22158092
TI  - Mechanisms and risk factors for noncontact ACL injury in age mature athletes who
      engage in field or court sports: a summary of the literature since 1980.
AB  - Epidemiological data show that in the last 10 years alone the incidence and rate
      of anterior cruciate ligament (ACL) injuries have not changed appreciably.
      Furthermore, many ACL injuries appear to be noncontact in nature and sustained
      while engaging in some field or court sport. Thus, the need to investigate novel
      methods and adopt training strategies to prevent ACL injuries is paramount. To do
      so, however, requires an understanding of the mechanisms and risk factors for the
      injury. The aim of this review was to investigate the mechanisms and risk factors
      for noncontact ACL injuries in age mature athletes who compete in field or court
      sports. A search of the entire MEDLINE database for biomedicine was performed,
      and an iterative reference check was also conducted. A total of 87 articles
      disclosed met the eligibility criteria. Articles were grouped into 'themes';
      'anatomical and biomechanical mechanisms and risk factors,' 'intrinsic mechanisms
      and risk factors,' and 'extrinsic mechanisms and risk factors.' In this review,
      it is concluded that there are still a number of risk factors and mechanisms for
      noncontact ACL injury that are not well understood. However, the importance of
      dynamic knee joint stability is highlighted. It is also suggested that novel
      methods for preventing ACL injury be investigated and developed.

PMID- 22158093
TI  - Short intervals between sets and individuality of muscle damage response.
AB  - This study examined creatine kinase (CK) activity after resistance exercise
      sessions in subjects classified as high (HiR), medium (MeR), or low responders
      (LoR). Two resistance exercise sessions were performed that each involved 4 sets
      of the biceps curl at 85% of a 1 repetition maximum (1RM) and either 1- or 3
      minute rest intervals between sets. High responders and MeR demonstrated
      significantly greater CK activity after the 1-minute session vs. the 3-minute
      session. Therefore, the HiR and MeR subjects exhibited less tolerance to resting
      1 minute between sets, whereas the CK activity was not significantly different
      between rest intervals for the LoR subjects. The application of these findings
      indicates the need to vary the length of the rest interval between sets with the
      understanding that individuals exhibit varying recuperative abilities and some
      might be less tolerant of shorter rest intervals between sets.

PMID- 22158094
TI  - A kinematic comparison of alterations to knee and ankle angles from resting
      measures to active pedaling during a graded exercise protocol.
AB  - Saddle height is one of the most researched areas of bike fit. The current
      accepted method for adjusting saddle height involves the use of a goniometer to
      adjust saddle height so that a knee angle between 25 degrees  and 35 degrees  is
      obtained. This measurement is taken while the cyclist maintains a static position
      with the pedal at the 6-o'-clock position. However, the act of pedaling is
      dynamic, and angles may alter during movement. The purpose of this study was to
      examine the alterations to knee and ankle angle occurring from static measures to
      active pedaling across intensities experienced by cyclists during a graded
      exercise protocol. Thirty-four recreational to highly trained cyclists were
      evaluated using 2D analysis of stationary position and 3 active levels (level 1,
      respiratory exchange ratio of 1.00, and max). Dependent measures were compared
      using repeated measures analysis of variance (p = 0.05). When examining the
      results, it is evident that significant alterations to pedal stroke occur from
      stationary measures to active pedaling and as intensity increases toward maximal.
      Plantar flexion increased when moving from stationary measures to active
      pedaling, which resulted in an increase in knee angle. Although still greater
      than stationary measures, less plantar flexion occurred at higher intensities
      when compared with lower intensity cycling. Less plantar flexion at higher
      intensities is most likely a result of application of a larger downward torque
      occurring because of greater power requirements at higher intensities. There
      appeared to be greater variability in angle when examining novice cyclists in
      relation to more experienced cyclists. Although stationary measures are where a
      bike fit session will begin, observation during the pedal cycle may be needed to
      fine-tune the riders' fit.

PMID- 22158095
TI  - The effects of two different arm positions and weight status on select kinematic
      variables during the bodyweight squat.
AB  - The bodyweight squat is a common movement and is safe and effective. There are
      many variations and techniques, but little research has explored alterations of
      the movement. The purpose of this study was to examine the effects of 2 arm
      positions on select kinematic variables during the bodyweight squat. The
      participants were classified as normal-weight (NW: n = 17, height: 1.67 +/- 0.06
      m, weight: 61.25 +/- 6.90 kg, body mass index [BMI]: 21.92 +/- 1.68) or
      overweight (OW: n = 11, height: 1.68 +/- 0.06 m, weight: 88.91 +/- 16.86 kg, BMI:
      31.64 +/- 6.06) according to BMI. The participants completed a bodyweight squat
      with the arms held at the sides (AP1) followed by a bodyweight squat with the
      arms held at shoulder level (AP2). Reflective markers were placed on the
      shoulder, hip, knee, base of the fifth toe, and heel. Data were recorded and
      analyzed using Peak 9. Trunk and knee flexion was analyzed using separate
      repeated measures analyses of variance. Overweight participants exhibited reduced
      knee (OW: 75.56 +/- 17.94 degrees ; NW: 83.73 +/- 13.03 degrees ; p < 0.05) and
      trunk flexion (OW: -78.18 +/- 17.72 degrees ; NW: -90.65 +/- 17.57 degrees ; p =
      0.05). Holding the arms at shoulder level resulted in greater knee flexion (AP1:
      80.81 +/- 15.17 degrees ; AP2: 86.31 +/- 15.21 degrees ; p < 0.01). Both weight
      status and arm position affected the range of motion in the bodyweight squat.
      Using an arms-up position should be considered, especially for the OW population,
      to increase the benefits of the bodyweight squat by increasing the range of
      motion.

PMID- 22158096
TI  - Influence of knee flexion angle and age on triceps surae muscle fatigue during
      heel raises.
AB  - The triceps surae (TS) muscle-tendon unit is 1 of the most commonly injured in
      elite and recreational athletes, with a high prevalence in middle-aged adults.
      The performance of maximal numbers of unilateral heel raises is used to assess,
      train, and rehabilitate TS endurance and conventionally prescribed in 0 degrees 
      knee flexion (KF) for the gastrocnemius and 45 degrees  for the soleus (SOL).
      However, the extent of muscle selectivity conferred through the change in the
      knee angle is lacking for heel raises performed to volitional fatigue. This study
      investigated the influence of knee angle on TS muscle fatigue during heel raises
      and determined whether fatigue differed between middle-aged and younger-aged
      adults. Forty-eight healthy individuals aged 18-25 and 35-45 years performed
      maximal numbers of unilateral heel raises in 0 degrees  and 45 degrees  KF.
      Median frequencies and linear regression slopes were calculated from the SOL,
      gastrocnemius medialis (GM), and gastrocnemius lateralis (GL) surface
      electromyographic signals. Stepwise mixed-effect regressions were used for
      analysis. The subjects completed an average of 45 and 48 heel raises in 0 degrees
      and 45 degrees  KF, respectively. The results indicated that the 3 muscles
      fatigued during testing as all median frequencies decreased, and regression
      slopes were negative. Consistent with muscle physiology and fiber typing, fatigue
      was greater in the GM and GL than in the SOL (p < 0.001). However, knee angle did
      not influence TS muscle fatigue parameters (p = 0.814), with similar SOL, GM, and
      GL fatigue in 0 degrees  and 45 degrees  KF. These findings are in contrast with
      the traditionally described clinical use of heel raises in select knee angles for
      the gastrocnemius and the SOL. Furthermore, no difference in TS fatigue between
      the 2 age groups was able to be determined, despite the reported higher
      prevalence of injury in middle-aged individuals.

PMID- 22158097
TI  - Rapid increase in training load affects markers of skeletal muscle damage and
      mechanical performance.
AB  - The aim of this study was to monitor the changes in indirect markers of muscle
      damage during 3 weeks (9 training sessions) of stretch-shortening (drop jump)
      exercise with constant load alternated with steep increases in load. Physically
      active men (n = 9, mean age 19.1 years) performed a program involving a rapid
      stepwise increase in the number of jumps, drop height, and squat depth, and the
      addition of weight. Concentric, isometric maximal voluntary contraction (MVC),
      and stimulated knee extension torque were measured before and 10 minutes after
      each session. Muscle soreness and plasma creatine kinase activity were assessed
      after each session. Steep increments in stretch-shortening exercise load in
      sessions 4 and 7 amplified the postexercise decrease in stimulated muscle torque
      and slightly increased muscle soreness but had a minimal effect on the recovery
      of MVC and stimulated torque. Maximal jump height increased by 7.8 +/- 6.3% (p <
      0.05), 11.4 +/- 3.3% (p < 0.05), and 12.8 +/- 3.6% (p < 0.05) at 3, 10, and 17
      days after the final training session, respectively. Gains in isometric knee
      extension MVC (7.9 +/- 8.2%) and 100-Hz-evoked torque (9.9 +/- 9.6%) (both p <
      0.05) were observed within 17 days after the end of the training. The magnitude
      of improvement was greater after this protocol than that induced by a continuous
      constant progression loading pattern with small gradual load increments in each
      training session. These findings suggest that plyometric training using
      infrequent but steep increases in loading intensity and volume may be beneficial
      to athletic performance.

PMID- 22158098
TI  - Running demands and heart rate responses in men Rugby Sevens.
AB  - The purpose of this study was to examine match running performance and exercise
      intensity in a Rugby Sevens (7s) team during competitive club-level matches. Time
      motion analyses (global position system) were performed on 7 male rugby players
      during 5 competitive matches in a 2-day tournament. The players covered an
      average distance of 1,580.8 +/- 146.3 m per game (14 minutes). Over this
      distance, 34.8% (549.7 +/- 79.1 m) was spent standing and walking, 26.2% (414.8
      +/- 105.1 m) jogging, 9.8% (154.6 +/- 53.5 m) cruising, 15.5% (244.5 +/- 80.1 m)
      striding, 5% (79.5 +/- 37.2 m) high-intensity running, and 8.7% (137.7 +/- 84.9
      m) sprinting. The average maximal distance of sprints, the number of sprints, the
      minimum distance of sprint, and the mean sprint distance over the game were 29.5
      +/- 11.7 m, 7.4 +/- 3.9 sprints, 9.1 +/- 5.7 m, and 18 +/- 7.6 m, respectively.
      The player's work-to-rest ratio was 1:0.5. For over 75% of the game, the players
      were exposed to heart rates (HRs) >80% of their maximal HR. There were no
      statistical differences between the first and second halves in any of the
      variables analyzed. This study indicates that the physical demands of Rugby 7s
      are quite different from those encountered in other rugby codes and that the
      training regimes need to meet the increased overall running demands, the
      augmented high-intensity running actions, and the reduced work-to-rest ratios.

PMID- 22158099
TI  - Physiological responses and time-motion characteristics of 4-a-side small-sided
      game in young soccer players:  the influence of different team formation methods.
AB  - The purpose of this study was to examine the influence of different team
      formation methods on the physiological responses to and time-motion
      characteristics of 4-a-side small-sided games (SSG4) in young soccer players.
      Thirty-two young soccer players (age 16.2 +/- 0.7 years; height 172.9 +/- 6.1 cm;
      body mass 64.1 +/- 7.7 kg) voluntarily participated in this study. Anthropometric
      measurements, technical tests, and maximum oxygen uptake (V[Combining Dot
      Above]O2max) tests were carried out on the players. The SSG4 teams were then
      created using 4 different methods: according to the coaches' subjective
      evaluation (CE), technical scores (TS), V[Combining Dot Above]O2max (AP), and
      V[Combining Dot Above]O2max multiplied by TSs (CG). The teams thus created played
      4 bouts of SSG4 at 2-day intervals. During the SSG4, heart rate (HR) responses,
      distance covered, and time spent in HRmax zones were recorded. In addition,
      rating of perceived exertion (RPE) and blood lactate level (La) were determined
      at the end of the last bout of each SSG4. Percent of HRmax (%HRmax), La, and RPE
      responses during SSG4 were significantly higher for teams chosen according to AP
      and CG compared with that according to CE and TS (p < 0.05). In addition, teams
      chosen by AP and CG spent significantly more time in zone 4 (>90% HRmax ) and
      covered a greater distance in the high-intensity running zone (>18 km.h) than did
      teams formed according to TS. Moreover, AP teams covered significantly greater
      total distance than TS teams did (p < 0.05). In conclusion, to spend more time in
      both the high-intensity HR zone and the high-intensity running zone, the teams in
      SSG4 should be formed according to the players' V[Combining Dot Above]O2max
      values or the values calculated using both the V[Combining Dot Above]O2max and
      technique scores.

PMID- 22158100
TI  - The sticking region in three chest-press exercises with increasing degrees of
      freedom.
AB  - The purpose was to investigate the effect of 3 chest-press exercises with
      different degrees of freedom upon the sticking region and muscle activity in
      maximal attempts. It was hypothesized that, with increasing degrees of freedom,
      the sticking region (the weakest region during the lift) would be longer because
      the muscles need to use a part of their ability to control these increasing
      degrees of freedom during the exercise. Furthermore, the prime movers would have
      the same muscle activity, but the biceps muscle activity would increase when the
      degrees of freedom increases because of the enhanced control of the upward
      movement. Eleven male subjects (age 22.6 +/- 1.7 years, body mass 78.6 +/- 8.0
      kg, stature 1.80 +/- 0.07 m) with at least 1 year of bench press training
      experience participated in this study. Every subject was tested in 1 repetition
      maximum (1RM) in the 3 chest-press exercises. During the attempts, kinematics and
      muscle activity were recorded and analyzed in 4 different regions (downward,
      presticking, sticking, and poststicking). The participants achieved the highest
      1RM strength using the free barbell (106.4 +/- 15.5 kg), followed by the Smith
      machine (103.6 +/- 14.8 kg) and dumbbells (89.5 +/- 13.7 kg). Furthermore, muscle
      activity differences (electromyographic) between the 3 different exercises and
      the muscle activation between the 4 different regions were found. The length of
      the different lifting regions together with muscle activity was different between
      the exercises. However, the differences found did not follow the line of
      increasing degrees of freedom that would result in a longer sticking region.
      Therefore, it is possible to choose to train a particular chest press exercise
      with the purpose of training a particular muscle more than the others.

PMID- 22158101
TI  - Kinematics analyses related to stretch-shortening cycle during soccer instep
      kicking after different acute stretching.
AB  - The purpose of this study was to examine the effects of static and dynamic
      stretching within a preexercise warm-up on angular velocity of knee joint,
      deepest knee flexion (DKF), and duration of eccentric and concentric
      contractions, which are relative to the stretch-shortening cycle (SSC) during
      instep kicking in professional soccer players. The kicking motions of dominant
      legs were captured from 18 Olympic professional male soccer players (height:
      180.38 +/- 7.34 cm; weight: 69.77 +/- 9.73 kg; age: 19.22 +/- 1.83 years) using 4
      digital video cameras at 50 Hz. There was a significant difference in the DKF
      after the dynamic stretching (-3.22 +/- 3.10 degrees ) vs. static stretching (
      0.18 +/- 3.19 degrees ) relative to the no-stretching method with p < 0.001.
      Moreover, there was significant difference in eccentric duration after the
      dynamic stretching (0.006 +/- 0.01 seconds) vs. static stretching (-0.003 +/-
      0.01 seconds) relative to the no-stretching method with p < 0.015. There was a
      significant difference in the concentric duration after the dynamic stretching (
      0.007 +/- 0.01 seconds) vs. static stretching (0.002 +/- 0.01 seconds) relative
      to the no-stretching method with p < 0.001. There was also a significant
      difference in knee angular velocity after the dynamic stretching (4.08 +/- 3.81
      rad.s) vs. static stretching (-5.34 +/- 4.40 rad.s) relative to the no-stretching
      method with p < 0.001. We concluded that dynamic stretching during warm-ups, as
      compared with static stretching, is probably the most effective way as
      preparation for the kinematics characteristics of soccer instep kick, which are
      relative to the SSC.

PMID- 22158102
TI  - Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive
      behaviour.
AB  - Drug-evoked synaptic plasticity is observed at many synapses and may underlie
      behavioural adaptations in addiction. Mechanistic investigations start with the
      identification of the molecular drug targets. Cocaine, for example, exerts its
      reinforcing and early neuroadaptive effects by inhibiting the dopamine
      transporter, thus causing a strong increase in mesolimbic dopamine. Among the
      many signalling pathways subsequently engaged, phosphorylation of the
      extracellular signal-regulated kinase (ERK) in the nucleus accumbens is of
      particular interest because it has been implicated in NMDA-receptor and type 1
      dopamine (D1)-receptor-dependent synaptic potentiation as well as in several
      behavioural adaptations. A causal link between drug-evoked plasticity at
      identified synapses and behavioural adaptations, however, is missing, and the
      benefits of restoring baseline transmission have yet to be demonstrated. Here we
      find that cocaine potentiates excitatory transmission in D1-receptor-expressing
      medium-sized spiny neurons (D1R-MSNs) in mice via ERK signalling with a time
      course that parallels locomotor sensitization. Depotentiation of cortical nucleus
      accumbens inputs by optogenetic stimulation in vivo efficiently restored normal
      transmission and abolished cocaine-induced locomotor sensitization. These
      findings establish synaptic potentiation selectively in D1R-MSNs as a mechanism
      underlying a core component of addiction, probably by creating an imbalance
      between distinct populations of MSNs in the nucleus accumbens. Our data also
      provide proof of principle that reversal of cocaine-evoked synaptic plasticity
      can treat behavioural alterations caused by addictive drugs and may inspire novel
      therapeutic approaches involving deep brain stimulation or transcranial magnetic
      stimulation.

PMID- 22158103
TI  - Interactions between cancer stem cells and their niche govern metastatic
      colonization.
AB  - Metastatic growth in distant organs is the major cause of cancer mortality. The
      development of metastasis is a multistage process with several rate-limiting
      steps. Although dissemination of tumour cells seems to be an early and frequent
      event, the successful initiation of metastatic growth, a process termed
      'metastatic colonization', is inefficient for many cancer types and is
      accomplished only by a minority of cancer cells that reach distant sites.
      Prevalent target sites are characteristic of many tumour entities, suggesting
      that inadequate support by distant tissues contributes to the inefficiency of the
      metastatic process. Here we show that a small population of cancer stem cells is
      critical for metastatic colonization, that is, the initial expansion of cancer
      cells at the secondary site, and that stromal niche signals are crucial to this
      expansion process. We find that periostin (POSTN), a component of the
      extracellular matrix, is expressed by fibroblasts in the normal tissue and in the
      stroma of the primary tumour. Infiltrating tumour cells need to induce stromal
      POSTN expression in the secondary target organ (in this case lung) to initiate
      colonization. POSTN is required to allow cancer stem cell maintenance, and
      blocking its function prevents metastasis. POSTN recruits Wnt ligands and thereby
      increases Wnt signalling in cancer stem cells. We suggest that the education of
      stromal cells by infiltrating tumour cells is an important step in metastatic
      colonization and that preventing de novo niche formation may be a novel strategy
      for the treatment of metastatic disease.

PMID- 22158104
TI  - A disinhibitory microcircuit for associative fear learning in the auditory
      cortex.
AB  - Learning causes a change in how information is processed by neuronal circuits.
      Whereas synaptic plasticity, an important cellular mechanism, has been studied in
      great detail, we know much less about how learning is implemented at the level of
      neuronal circuits and, in particular, how interactions between distinct types of
      neurons within local networks contribute to the process of learning. Here we show
      that acquisition of associative fear memories depends on the recruitment of a
      disinhibitory microcircuit in the mouse auditory cortex. Fear-conditioning
      associated disinhibition in auditory cortex is driven by foot-shock-mediated
      cholinergic activation of layer 1 interneurons, in turn generating inhibition of
      layer 2/3 parvalbumin-positive interneurons. Importantly, pharmacological or
      optogenetic block of pyramidal neuron disinhibition abolishes fear learning.
      Together, these data demonstrate that stimulus convergence in the auditory cortex
      is necessary for associative fear learning to complex tones, define the circuit
      elements mediating this convergence and suggest that layer-1-mediated
      disinhibition is an important mechanism underlying learning and information
      processing in neocortical circuits.

PMID- 22158105
TI  - Fast core rotation in red-giant stars as revealed by gravity-dominated mixed
      modes.
AB  - When the core hydrogen is exhausted during stellar evolution, the central region
      of a star contracts and the outer envelope expands and cools, giving rise to a
      red giant. Convection takes place over much of the star's radius. Conservation of
      angular momentum requires that the cores of these stars rotate faster than their
      envelopes; indirect evidence supports this. Information about the angular
      momentum distribution is inaccessible to direct observations, but it can be
      extracted from the effect of rotation on oscillation modes that probe the stellar
      interior. Here we report an increasing rotation rate from the surface of the star
      to the stellar core in the interiors of red giants, obtained using the rotational
      frequency splitting of recently detected 'mixed modes'. By comparison with
      theoretical stellar models, we conclude that the core must rotate at least ten
      times faster than the surface. This observational result confirms the theoretical
      prediction of a steep gradient in the rotation profile towards the deep stellar
      interior.

PMID- 22158106
TI  - Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing
      inflammatory cytokines and HMGB1.
AB  - AIM: To investigate the neuroprotective effect of glycyrrhizin (Gly) against the
      ischemic injury of rat spinal cord and the possible role of the nuclear protein
      high-mobility group box 1 (HMGB1) in the process. METHODS: Male Sprague-Dawley
      rats were subjected to 45 min aortic occlusion to induce transient lumbar spinal
      cord ischemia. The motor functions of the animals were assessed according to the
      modified Tarlov scale. The animals were sacrificed 72 h after reperfusion and the
      lumbar spinal cord segment (L2-L4) was taken out for histopathological
      examination and Western blotting analysis. Serum inflammatory cytokine and HMGB1
      levels were analyzed using ELISA. RESULTS: Gly (6 mg/kg) administered
      intravenously 30 min before inducing the transient lumbar spinal cord ischemia
      significantly improved the hind-limb motor function scores, and reduced the
      number of apoptotic neurons, which was accompanied by reduced levels of tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6
      (IL-6) in the plasma and injured spinal cord. Moreover, the serum HMGB1 level
      correlated well with the serum TNF-alpha, IL-1beta and IL-6 levels during the
      time period of reperfusion. CONCLUSION: The results suggest that Gly can
      attenuate the transient spinal cord ischemic injury in rats via reducing
      inflammatory cytokines and inhibiting the release of HMGB1.

PMID- 22158107
TI  - Autophagy counteracts apoptosis in human multiple myeloma cells exposed to
      oridonin in vitro via regulating intracellular ROS and SIRT1.
AB  - AIM: To explore the mechanisms underlying the oridonin-induced apoptosis and
      autophagy in human multiple myeloma cells in vitro. METHODS: Human multiple
      myeloma RPMI8266 cells were used. The cell viability was assessed using MTT
      assay. Morphological changes of apoptosis and autophagy were observed under
      transmission electron microscope. TUNEL and annexin V-FITC/PI dual staining
      assays were used to measure apoptosis. Autophagy was analyzed using Western blot
      analysis and immunofluorescence staining with a QDs(605 nm)-Anti-LC3 fluorescent
      probe. Intracellular ROS was estimated with flow cytometry using DCFH-DA
      fluorescent probe. Protein levels of active caspase 3, Beclin 1 and SIRT1 were
      determined with Western blot analysis. RESULTS: Exposure to oridonin (1-64
      MUmol/L) inhibited the proliferation of RPMI8266 cells in a concentration
      dependent manner with an IC(50) value of 6.74 MUmol/L. Exposure to oridonin (7
      MUmol/L) simultaneously induced caspase 3-mediated apoptosis and Beclin 1
      dependent autophagy of RPMI8266 cells. Both the apoptosis and autophagy were time
      dependent, and apoptosis was the main effector pathway of cell death. Exposure to
      oridonin (7 MUmol/L) increased intracellular ROS and reduced SIRT1 nuclear
      protein in a time-dependent manner. The blockade of intracellular generation of
      ROS by NAC (5 mmol/L) abrogated apoptosis, autophagy and the decrease of SIRT1 in
      the cells exposed to oridonin (7 MUmol/L). The inhibition of autophagy by 3-MA (5
      mmol/L) sensitized the cells to oridonin-induced apoptosis, which was accompanied
      by increased intracellular ROS and decreased SIRT1. CONCLUSION: Oridonin
      simultaneously induces apoptosis and autophagy of human multiple myeloma RPMI8266
      cells via regulation of intracellular ROS generation and SIRT1 nuclear protein.
      The cytotoxicity of oridonin is mainly mediated through the apoptotic pathway,
      whereas the autophagy protects the cells from apoptosis.

PMID- 22158108
TI  - Suppression of human lung cancer cell proliferation and metastasis in vitro by
      the transducer of ErbB-2.1 (TOB1).
AB  - AIM: To investigate the effects of the transducer of ErbB-2.1 (TOB1) on the
      proliferation, migration and invasion of human lung cancer cells in vitro.
      METHODS: Human lung cancer cell lines (95-D, A549, NCI-H1299, NCI-H1975, NCI
      H661, NCI-H446, NCI-H1395, and Calu-3) and the normal human bronchial epithelial
      (HBE) cell line were tested. The expression levels of TOB1 in the cells were
      determined with Western blot and RT-PCR analyses. TOB1-overexpressing cell line
      95-D/TOB1 was constructed using lipofectamine-induced TOB1 recombinant plasmid
      transfection and selective G418 cell culture. The A549 cells were transcend
      transfected with TOB1-siRNA. MTT assay, flow cytometry and Western blot analysis
      were used to examine the effects of TOB1 on cancer cell proliferation and wound
      healing. Transwell invasive assay was performed to evaluate the effects of TOB1
      on cancer cell migration and invasion. The activity of MMP2 and MMP9 was measured
      using gelatin zymography assay. RESULTS: The expression levels of TOB1 in the 8
      human lung cancer cell lines were significantly lower than that in HBE cells.
      TOB1 overexpression inhibited the proliferation of 95-D cells, whereas TOB1
      knockdown with TOB1-siRNA promoted the growth of A549 cells. Decreased cell
      migration and invasion were detected in 95-D/TOB1 cells, and the suppression of
      TOB1 enhanced the metastasis in A549 cells. TOB1 overexpression not only
      increased the expression of the phosphatase and tensin homolog (PTEN), an
      important tumor suppressor, but also regulated the downstream effectors in the
      PI3K/PTEN signaling pathway, including Akt, ERK1/2, etc. In contrast, decreased
      expression of TOB1 oppositely regulated the expression of these factors. TOB1
      also regulates the gelatinase activity of MMP2 and MMP9 in lung cancer cells.
      CONCLUSION: The results demonstrate that the PI3K/PTEN pathway, which is
      essential for carcinogenesis, angiogenesis, and metastasis, may be one of the
      possible signaling pathways for regulation of proliferation and metastasis of
      human lung cancer cells by TOB1 in vitro.

PMID- 22158109
TI  - Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated
      rabbits under mechanical ventilation.
AB  - AIM: To explore the mechanisms underlying the propofol infusion syndrome (PRIS),
      a potentially fatal complication during prolonged propofol infusion. METHODS:
      Male rabbits under mechanical ventilation through endotracheal intubation were
      divided into 3 groups (n=6 for each) that were sedated with 1% propofol (Group
      P), isoflurane (Group I) or isoflurane while receiving 10% intralipid (Group II),
      respectively. Blood biochemical parameters were collected at 0, 6, 12, 18, 24 and
      30-36 h after the initiation of treatments. The hearts were removed out
      immediately after the experiments, and the level of tumor necrosis factor (TNF)
      alpha in the hearts were studied using immunohistochemistry. AMP-activated
      protein kinase (AMPK) and phospho-AMPK in the hearts were assessed using Western
      blotting. RESULTS: The mortality rate was 50% in Group P, and 0% in Groups I and
      II. The serum lipids and liver function indices in Group P were significantly
      increased, but moderately increased in Group II. Significant decreases in these
      indices were found in Groups I. All the groups showed dramatically increased
      release of creatine kinase (CK). Intense positive staining of TNF-alpha was found
      in all the heart samples in Group P, but only weak and neglectful staining was
      found in the hearts from Group II and Group I, respectively. AMPK phosphorylation
      was significantly increased in the hearts of Group P. CONCLUSION: Continuous
      infusion of large dose of propofol in rabbits undergoing prolonged mechanical
      ventilation causes hyperlipidemia, liver dysfunction, increased CK levels, AMPK
      activation and myocardial injury. The imbalance between energy demand and
      utilization may contribute to PRIS.

PMID- 22158110
TI  - The C718T polymorphism in the 3'-untranslated region of glutathione peroxidase-4
      gene is a predictor of cerebral stroke in patients with essential hypertension.
AB  - In the present study we have investigated the association of three single
      nucleotide polymorphisms in glutathione peroxidase (GPx) genes GPX1 rs1050450
      (P198L), GPX3 rs2070593 (G930A) and GPX4 rs713041 (T718C) with the risk of
      cerebral stroke (CS) in patients with essential hypertension (EH). A total of 667
      unrelated EH patients of Russian origin, including 306 hypertensives (the EH-CS
      group) who suffered from CS and 361 people (the EH-CS group) who did not have
      cerebrovascular accidents, were enrolled in the study. The variant allele 718C of
      the GPX4 gene was found to be significantly associated with an increased risk of
      CS in hypertensive patients (odds ratio (OR) 1.53, 95% confidence interval (CI)
      1.23-1.90, P(adj) = 0.0003). The prevalence of the 718TC and 718CC genotypes of
      the GPX4 gene was higher in the EH-CS group than the EH-alone group (OR = 2.12,
      95%CI 1.42-3.16, P(adj) = 0.0018). The association of the variant GPX4 genotypes
      with the increased risk of CS in hypertensives remained statistically significant
      after adjusting for confounding variables such as sex, body mass index (BMI),
      blood pressure and antihypertensive medication use (OR = 2.18, 95%CI 1.46-3.27, P
      = 0.0015). Multiple logistic regression analysis did not reveal any interaction
      between various combinations of GPX1, GPX3 and GPX4 genotypes regarding the risk
      of CS in patients with EH. The study demonstrated for the first time that the
      C718T polymorphism in the 3'-untranslated region of the GPX4 gene could be
      considered as a genetic marker of susceptibility to CS in patients with EH.

PMID- 22158111
TI  - Vaccination against the angiotensin type 1 receptor for the prevention of L-NAME
      induced nephropathy.
AB  - Previous studies have shown that renin-angiotensin (Ang) system vaccines may be
      effective for the treatment of hypertension, but their efficacy for the
      prevention of renal disease is unclear. The aim of this study was to compare the
      effects of an Ang II type 1 (AT1) receptor vaccine with an Ang II receptor
      blocker (ARB) and a vasodilator on blood pressure (BP) and renal injury in the L
      NAME nephropathy model. Male spontaneously hypertensive rats (SHRs) were divided
      into six groups and treated transiently with three injections of vehicle or AT1
      receptor vaccine (0.1 mg) at age 4, 6 and 8 weeks, or continuously with
      candesartan cilexetil (0.1 mg kg(-1) per day) or hydralazine hydrochloride (5 mg
      kg(-1) per day), then administered NG-nitro-L-arginine methyl ester (L-NAME) from
      age 18 to 21 weeks to induce renal injury. Vaccination against the AT1 receptor
      caused a significant increase in AT1 receptor titers, and a sustained decrease in
      BP. L-NAME treatment resulted in a marked increase in proteinuria in the control
      groups, which was completely suppressed in the AT1 vaccine-treated group, and
      glomerular injury scores were also significantly decreased. Real-time RT-PCR and
      immunofluorescence studies revealed increased renin mRNA, and increased
      glomerular expression of nephrin. Comparable results were seen in rats treated
      continuously with the ARB candesartan, but not with hydralazine. These results
      suggest that transient AT1 vaccination is as effective as continuous treatment
      with ARB, not only for the attenuation of hypertension, but also for the
      prevention of L-NAME-induced nephropathy in SHR.

PMID- 22158112
TI  - A comparison between central blood pressure values obtained by the Gaon system
      and the SphygmoCor system.
AB  - Central pulse pressure is correlated with carotid atherosclerosis and the
      incidence of cardiovascular events more significantly than brachial pulse
      pressure. Augmentation index (Aix) has been shown to be an independent predictor
      of cardiovascular morbidity and mortality. Pulse wave analysis using the Gaon
      system allows for the estimation of central blood pressure (CBP), corrected
      augmentation index (Aix@HR75), ejection duration (ED) and subendocardial
      viability ratio (SEVR), and is widely used in clinical research in Korea.
      However, the accuracy of this system is controversial. From February 2008 to
      March 2011, 99 patients were recruited for this study. Measurements were taken
      both by the Gaon system and the SphygmoCor system on the same day for all study
      participants. The estimated values of CBP, Aix@HR75, ED and SEVR for the two
      systems were compared using paired t-tests, simple correlation analyses and Bland
      Altman plots. Systolic blood pressure (SBP) estimated by the two systems was
      significantly (P<0.001) correlated; the coefficient was 0.982. The two s.d. of
      the difference in SBP between these systems was quite small--<7 mm Hg. Aix@HR75,
      ED and SEVR as estimated by the two systems were also significantly correlated,
      although they, especially SEVR, showed much weaker correlations than were
      observed in SBP: coefficients for Aix@HR75, ED and SEVR were 0.727, 0.648 and
      0.230, respectively. We assessed the CBP of Korean patients estimated by the two
      systems and observed that the correlations of Aix, ED and SEVR were weaker than
      that of CBP. Such variations may be due to the difference in measuring methods
      between the devices. As even a slight change in pulse waveforms may result in a
      large difference in estimations, parameters, including Aix@HR75, ED and SEVR,
      should be carefully interpreted by experienced clinicians.

PMID- 22158113
TI  - Cigarette smoking and chronic kidney diseases.
AB  - Observational studies have suggested that different chronic kidney diseases
      (CKDs) have differing relationships to smoking, but no randomized controlled
      trial has been conducted to examine this topic. In this article, we review
      available evidence concerning the relationship between smoking and each type of
      CKD in the general population as well as in patients with diabetes mellitus (DM),
      hypertension (HT), primary glomerulonephritis and kidney transplants. There is
      good evidence of a relationship between smoking and CKD in patients with IgA
      nephropathy and kidney transplant recipients, but not in patients with DM or HT.
      Interestingly, it has been reported that the effect of smoking on CKD progression
      varies depending on the CKD stage. This variation might indicate a cumulative
      effect of smoking, possibly through oxidative stress. A better understanding of
      the relationship between smoking and CKD would be useful for nephrologists.

PMID- 22158114
TI  - Tonic activity of carotid body chemoreceptors contributes to the increased
      sympathetic drive in essential hypertension.
AB  - Carotid chemoreceptors provoke an increase in muscle sympathetic nerve activation
      (MSNA) in response to hypoxia; they are also tonically active during normoxic
      breathing. The contribution of peripheral chemoreceptors to sympathetic
      activation in hypertension is incompletely understood. The aim of our study was
      to investigate the effect of chemoreceptor deactivation on sympathetic activity
      in untreated patients with hypertension. A total of 12 untreated hypertensive
      males and 11 male controls participated in this randomized, crossover, placebo
      controlled study. MSNA, systolic blood pressure(BP), diastolic BP, heart rate
      (HR), electrocardiogram, hemoglobin oxygen saturation (Sat%) and respiratory
      movements were measured during repeated 10-min periods of respiration with 100%
      oxygen or 21% oxygen in a blinded fashion. Compared with controls, hypertensives
      had higher resting MSNA (38 +/- 10 vs. 29 +/- 0.9 burst per min, P<0.05),
      systolic BP (150 +/- 12 vs. 124 +/- 10 mm Hg, P< 0.001) and diastolic BP (92 +/-
      10 vs. 77 +/- 9 mm Hg, P<0.005). Breathing 100% oxygen caused significant
      decrease in MSNA in hypertensive patients (38 +/- 10 vs. 26 +/- 8 burst per min
      and 100 +/- 0 vs. 90 +/- 10 arbitrary units, P<0.05) and no change in controls
      (29 +/- 9 vs. 27 +/- 7 burst per min and 100 +/- 0 vs. 96 +/- 11 arbitrary
      units). BP, respiratory frequency and end tidal CO(2) did not change during
      chemoreceptor deactivation with hyperoxia. HR decreased and Sat% increased in
      both the study groups. These results confirm the role of tonic chemoreceptor
      drive in the development of sympathetic overactivity in hypertension.

PMID- 22158115
TI  - Management of hypertension in women.
AB  - A gender-specific approach to cardiovascular (CV) diseases has been practiced for
      decades, although not always to the advantage of women. Based on population data
      showing that women are at lower risk for CV events than men female gender has
      generally been regarded as a protective factor for CV disease. Unfortunately, CV
      risk assessment has therefore received less attention in women. Despite the lower
      absolute risk of CV events in women compared with age-matched men, the majority
      of women die from CV diseases. In absolute numbers, since 1984, more women than
      men died of CV disease each year. Most CV events occur in women with known
      traditional CV risk factors. Improving risk factor management in women of all
      ages therefore yields an enormous potential to reduce CV morbidity and mortality
      in the population. Aside from smoking cessation, hypertension (HTN) control is
      the single most important intervention to reduce the risk of future CV events in
      women. This review highlights peculiarities of HTN as they pertain to women, and
      points out where diagnosis and management of HTN may require a gender-specific
      focus.

PMID- 22158116
TI  - A common missense single nucleotide polymorphism in the E-selectin gene is
      significantly associated with essential hypertension in the Han population but
      only weakly associated in the Uygur population.
AB  - Experimental and clinical observations suggest that E-selectin could have an
      important role in essential hypertension (EH), but the relationship between
      common E-selectin variants and EH has not been extensively studied in the Chinese
      population. In this study, we explored the association between two common
      variants in the E-selectin gene (rs5361A/C and rs5355C/T) and EH in the Uygur,
      Kazakh and Han populations in the Xinjiang area. A case-control study was
      conducted to explore the association between these two single-nucleotide
      polymorphisms and EH in a large sample size, including 941 EH subjects (309
      Uygur, 264 Kazakh and 368 Han individuals) and 924 control subjects (300 Uygur,
      275 Kazakh and 349 Han individuals). Univariate analysis showed that the rs5361
      A/C polymorphism was significantly associated with EH in the Uygur (P=0.002) and
      Han (P=3.6 * 10(-7)) populations. The CC genotype of this SNP was present only in
      patients with EH in all of the three nationalities studied. Han individuals who
      carry the CC genotype of rs5361 were more susceptible to EH, according to the
      dominant models (P=1.13 * 10(-4), odds ratio=3.812, 95% confidence interval:
      1.685-7.792), but there was no association of genotype with EH for the other
      ethnicities. No significant difference in rs5355 C/T polymorphism rate was found
      between the EH and control groups. Our results indicate that the common variant
      rs5361 is strongly associated with EH in Han individuals and weakly associated in
      Uygur individuals. The CC genotype of rs5361 might be an independent risk factor
      for EH among Uygur, Kazakh and Han individuals in the Xinjiang area.

PMID- 22158117
TI  - Baro-excited neurons in the caudal ventrolateral medulla (CVLM) recorded using
      the whole-cell patch-clamp technique.
AB  - Caudal ventrolateral medulla (CVLM) neurons have important roles in the
      regulation of sympathetic nerve activity and blood pressure through their tonic
      inhibition of rostral ventrolateral medulla neurons. As few reports have
      demonstrated CVLM neuronal activity using the whole-cell patch-clamp technique,
      we attempted to find neurons in the CVLM that are depolarized by the stimulation
      of baroreceptors. To record the membrane potentials of the neurons in the CVLM,
      we developed a modified brainstem-spinal cord preparation that enabled us to
      change the pressure exerted on the aortic arch and carotid sinuses. We were able
      to identify neurons in the CVLM in which they were depolarized and the action
      potential (AP) frequency was increased upon baroreceptor stimulation. We referred
      to these neurons as baro-excited CVLM neurons. When these preparations were
      superfused with an angiotensin-II (Ang-II) solution, the frequency of the APs
      increased in 10 of the 14 baro-excited CVLM neurons. Superfusion with a low
      Ca(2+), high-Mg(2+) solution abolished the APs in all seven baro-excited CVLM
      neurons, suggesting that the baro-excited CVLM neurons did not fire
      spontaneously. When the preparation was superfused with a low-Ca(2+) solution, 6
      of the 7 baro-excited CVLM neurons did not respond to Ang-II superfusion. We for
      the first time found the baro-excited CVLM neurons, which depolarized pressure
      dependently but may not fire spontaneously. As Ang-II did not change the activity
      of the CVLM neurons during superfusion with a low-Ca(2+), high-Mg(2+) solution,
      the presynaptic neurons may be mandatory for the Ang-II-induced activation of
      postsynaptic baro-excited CVLM neurons.

PMID- 22158120
TI  - Use of discard pleural fluid in molecular research.

PMID- 22158118
TI  - Single cell fate mapping in zebrafish.
AB  - The ability to differentially label single cells has important implications in
      developmental biology. For instance, determining how hematopoietic, lymphatic,
      and blood vessel lineages arise in developing embryos requires fate mapping and
      lineage tracing of undifferentiated precursor cells. Recently, photoactivatable
      proteins which include: Eos, PAmCherry, Kaede, pKindling, and KikGR have received
      wide interest as cell tracing probes. The fluorescence spectrum of these
      photosensitive proteins can be easily converted with UV excitation, allowing a
      population of cells to be distinguished from adjacent ones. However, the
      photoefficiency of the activated protein may limit long-term cell tracking. As an
      alternative to photoactivatable proteins, caged fluorescein-dextran has been
      widely used in embryo model systems. Traditionally, to uncage fluorescein
      dextran, UV excitation from a fluorescence lamp house or a single photon UV laser
      has been used; however, such sources limit the spatial resolution of
      photoactivation. Here we report a protocol to fate map, lineage trace, and detect
      single labeled cells. Single cells in embryos injected with caged fluorescein
      dextran are photoactivated with near-infrared laser pulses produced from a
      titanium sapphire femtosecond laser. This laser is customary in all two-photon
      confocal microscopes such as the LSM 510 META NLO microscope used in this paper.
      Since biological tissue is transparent to near-infrared irradiation, the laser
      pulses can be focused deep within the embryo without uncaging cells above or
      below the selected focal plane. Therefore, non-linear two-photon absorption is
      induced only at the geometric focus to uncage fluorescein-dextran in a single
      cell. To detect the cell containing uncaged fluorescein-dextran, we describe a
      simple immunohistochemistry protocol to rapidly visualize the activated cell. The
      activation and detection protocol presented in this paper is versatile and can be
      applied to any model system.

PMID- 22158121
TI  - DCC constrains tumour progression via its dependence receptor activity.
AB  - The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been
      a matter of debate for the past 15 years. DCC gene expression is lost or markedly
      reduced in the majority of advanced colorectal cancers and, by functioning as a
      dependence receptor, DCC has been shown to induce apoptosis unless engaged by its
      ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view
      that the DCC loss-of-function is causally implicated as predisposing to
      aggressive cancer development. To investigate the role of DCC-induced apoptosis
      in the control of tumour progression, here we created a mouse model in which the
      pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC
      induced apoptosis in this mouse model is not associated with a major
      disorganization of the intestines, it leads to spontaneous intestinal neoplasia
      at a relatively low frequency. Loss of DCC-induced apoptosis is also associated
      with an increase in the number and aggressiveness of intestinal tumours in a
      predisposing APC mutant context, resulting in the development of highly invasive
      adenocarcinomas. These results demonstrate that DCC functions as a tumour
      suppressor via its ability to trigger tumour cell apoptosis.

PMID- 22158122
TI  - Cysteine methylation disrupts ubiquitin-chain sensing in NF-kappaB activation.
AB  - NF-kappaB is crucial for innate immune defence against microbial infection.
      Inhibition of NF-kappaB signalling has been observed with various bacterial
      infections. The NF-kappaB pathway critically requires multiple ubiquitin-chain
      signals of different natures. The question of whether ubiquitin-chain signalling
      and its specificity in NF-kappaB activation are regulated during infection, and
      how this regulation takes place, has not been explored. Here we show that human
      TAB2 and TAB3, ubiquitin-chain sensory proteins involved in NF-kappaB signalling,
      are directly inactivated by enteropathogenic Escherichia coli NleE, a conserved
      bacterial type-III-secreted effector responsible for blocking host NF-kappaB
      signalling. NleE harboured an unprecedented S-adenosyl-l-methionine-dependent
      methyltransferase activity that specifically modified a zinc-coordinating
      cysteine in the Npl4 zinc finger (NZF) domains in TAB2 and TAB3. Cysteine
      methylated TAB2-NZF and TAB3-NZF (truncated proteins only comprising the NZF
      domain) lost the zinc ion as well as the ubiquitin-chain binding activity.
      Ectopically expressed or type-III-secretion-system-delivered NleE methylated TAB2
      and TAB3 in host cells and diminished their ubiquitin-chain binding activity.
      Replacement of the NZF domain of TAB3 with the NleE methylation-insensitive Npl4
      NZF domain resulted in NleE-resistant NF-kappaB activation. Given the prevalence
      of zinc-finger motifs and activation of cysteine thiol by zinc binding,
      methylation of zinc-finger cysteine might regulate other eukaryotic pathways in
      addition to NF-kappaB signalling.

PMID- 22158123
TI  - An unanticipated architecture of the 750-kDa alpha6beta6 holoenzyme of 3
      methylcrotonyl-CoA carboxylase.
AB  - 3-Methylcrotonyl-CoA carboxylase (MCC), a member of the biotin-dependent
      carboxylase superfamily, is essential for the metabolism of leucine, and
      deficient mutations in this enzyme are linked to methylcrotonylglycinuria (MCG)
      and other serious diseases in humans. MCC has strong sequence conservation with
      propionyl-CoA carboxylase (PCC), and their holoenzymes are both 750-kilodalton
      (kDa) alpha(6)beta(6) dodecamers. Therefore the architecture of the MCC
      holoenzyme is expected to be highly similar to that of PCC. Here we report the
      crystal structures of the Pseudomonas aeruginosa MCC (PaMCC) holoenzyme, alone
      and in complex with coenzyme A. Surprisingly, the structures show that the
      architecture and overall shape of PaMCC are markedly different when compared to
      PCC. The alpha-subunits show trimeric association in the PaMCC holoenzyme,
      whereas they have no contacts with each other in PCC. Moreover, the positions of
      the two domains in the beta-subunit of PaMCC are swapped relative to those in
      PCC. This structural information establishes a foundation for understanding the
      disease-causing mutations of MCC and provides new insights into the catalytic
      mechanism and evolution of biotin-dependent carboxylases. The large structural
      differences between MCC and PCC also have general implications for the
      relationship between sequence conservation and structural similarity.

PMID- 22158124
TI  - Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut.
AB  - The largest mucosal surface in the body is in the gastrointestinal tract, a
      location that is heavily colonized by microbes that are normally harmless. A key
      mechanism required for maintaining a homeostatic balance between this microbial
      burden and the lymphocytes that densely populate the gastrointestinal tract is
      the production and transepithelial transport of poly-reactive IgA (ref. 1).
      Within the mucosal tissues, B cells respond to cytokines, sometimes in the
      absence of T-cell help, undergo class switch recombination of their
      immunoglobulin receptor to IgA, and differentiate to become plasma cells.
      However, IgA-secreting plasma cells probably have additional attributes that are
      needed for coping with the tremendous bacterial load in the gastrointestinal
      tract. Here we report that mouse IgA(+) plasma cells also produce the
      antimicrobial mediators tumour-necrosis factor-alpha (TNF-alpha) and inducible
      nitric oxide synthase (iNOS), and express many molecules that are commonly
      associated with monocyte/granulocytic cell types. The development of iNOS
      producing IgA(+) plasma cells can be recapitulated in vitro in the presence of
      gut stroma, and the acquisition of this multifunctional phenotype in vivo and in
      vitro relies on microbial co-stimulation. Deletion of TNF-alpha and iNOS in B
      lineage cells resulted in a reduction in IgA production, altered diversification
      of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings
      reveal a novel adaptation to maintaining homeostasis in the gut, and extend the
      repertoire of protective responses exhibited by some B-lineage cells.

PMID- 22158126
TI  - Re: promoting healthy skepticism in the news: helping journalists get it right.

PMID- 22158125
TI  - Legume, soy, tofu, and isoflavone intake and endometrial cancer risk in
      postmenopausal women in the multiethnic cohort study.
AB  - BACKGROUND: Phytochemicals found in soy and other legumes have been speculated to
      reduce the risk of endometrial cancer; however, inconsistent findings have been
      reported in the few epidemiological studies conducted to date. METHODS: We
      conducted a prospective analysis of 46 027 nonhysterectomized postmenopausal
      women who were recruited into the Multiethnic Cohort (MEC) Study between August
      1993 and August 1996 and provided detailed baseline information on diet and other
      endometrial cancer risk factors. A total of 489 women diagnosed with incident
      endometrial cancer were identified through the Surveillance, Epidemiology, and
      End Results tumor registry linkages during a median follow-up period of 13.6
      years. Cox proportional hazards models were used to estimate multivariable
      adjusted relative risks (RRs) and 95% confidence intervals (CIs) for endometrial
      cancer associated with dietary intake of legumes, soy, and tofu, and for total
      isoflavones and specific isoflavones (daidzein, genistein, or glycitein).
      Truncated (age 50-89 years) age-adjusted incidence rates were calculated by
      applying age-specific rates within isoflavone quintiles to the overall MEC
      population eligible for endometrial cancer. To estimate the percentage of
      endometrial cancers that may have been prevented by consuming the highest
      quintile of total isoflavones, the partial population attributable risk percent
      was calculated. RESULTS: A reduced risk of endometrial cancer was associated with
      total isoflavone intake (highest vs lowest quintile, >=7.82 vs <1.59 mg per 1000
      kcal/d, RR = 0.66, 95% CI = 0.47 to 0.91), daidzein intake (highest vs lowest
      quintile, >=3.54 vs <0.70 mg per 1000 kcal/d, RR = 0.64, 95% CI = 0.46 to 0.90),
      and genistein intake (highest vs lowest quintile, >=3.40 vs <0.69 mg per 1000
      kcal/d, RR = 0.66, 95% CI = 0.47 to 0.91). No statistically significant
      association with endometrial cancer risk was observed for increasing intake of
      legumes, soy, tofu, or glycitein. Truncated age-adjusted incidence rates of
      endometrial cancer for the highest vs lowest quintile of total isoflavone intake
      were 55 vs 107 per 100 000 women per year, respectively. The partial population
      attributable risk percent for total isoflavone intake lower than the highest
      quintile was 26.7% (95% CI = 5.3% to 45.8%). CONCLUSION: This study suggests that
      greater consumption of isoflavone-containing foods is associated with a reduced
      risk of endometrial cancer in this population of nonhysterectomized
      postmenopausal women.

PMID- 22158127
TI  - Preventable exposures associated with human cancers.
AB  - Information on the causes of cancer at specific sites is important to cancer
      control planners, cancer researchers, cancer patients, and the general public.
      The International Agency for Research on Cancer (IARC) Monograph series, which
      has classified human carcinogens for more than 40 years, recently completed a
      review to provide up-to-date information on the cancer sites associated with more
      than 100 carcinogenic agents. Based on IARC's review, we listed the cancer sites
      associated with each agent and then rearranged this information to list the known
      and suspected causes of cancer at each site. We also summarized the rationale for
      classifications that were based on mechanistic data. This information, based on
      the forthcoming IARC Monographs Volume 100, offers insights into the current
      state-of-the-science of carcinogen identification. Use of mechanistic data to
      identify carcinogens is increasing, and epidemiological research is identifying
      additional carcinogens and cancer sites or confirming carcinogenic potential
      under conditions of lower exposure. Nevertheless, some common human cancers still
      have few (or no) identified causal agents.

PMID- 22158128
TI  - An introduction to model-independent diffusion magnetic resonance imaging.
AB  - q-Space-based techniques such as diffusion spectrum imaging, q-ball imaging, and
      their variations have been used extensively in research for their desired
      capability to delineate complex neuronal architectures such as multiple fiber
      crossings in each of the image voxels. The purpose of this article was to provide
      an introduction to the q-space formalism and the principles of basic q-space
      techniques together with the discussion on the advantages as well as challenges
      in translating these techniques into the clinical environment. A review of the
      currently used q-space-based protocols in clinical research is also provided.

PMID- 22158129
TI  - Challenges of High-resolution Diffusion Imaging of the Human Medial Temporal Lobe
      in Alzheimer Disease.
AB  - The human medial temporal lobe performs an essential role in memory formation
      and retrieval. Diseases involving the hippocampus such as Alzheimer disease
      present a unique opportunity for advanced imaging techniques to detect
      abnormalities at an early stage. In particular, it is possible that diffusion
      imaging will measure abnormal microarchitecture beyond the realm of macroscopic
      imaging. However, this task is formidable because of the detailed anatomy of the
      medial temporal lobe, the difficulties in obtaining high-quality diffusion images
      of adequate resolution, and the challenges in diffusion data processing.
      Moreover, it is unclear if any differences will be significant for an individual
      patient or simply groups of patients. Successful endeavors will need to address
      each of these challenges in an integrated fashion. The rewards of such analysis
      may be detection of microscopic disease in vivo, which could represent a landmark
      accomplishment for the field of neuroradiology.

PMID- 22158132
TI  - Fetal diffusion imaging: pearls and solutions.
AB  - Recently, diffusion-weighted (DWI) magnetic resonance imaging of the fetus has
      evolved from a basic research application to an important diagnostic imaging tool
      in fetal magnetic resonance imaging. Although technically challenging and still
      plagued with several sources of artifacts, DWI can add clinically important
      information, which cannot be provided by any other prenatal imaging modality. Its
      potential to noninvasively probe tissue structures on the basis of Brownian
      molecular motion enables the detection of early changes associated with acute
      fetal diseases, as well as structural alterations of functionally diverse
      compartments of different fetal organs. In this article, the current clinical
      applications of fetal brain and body DWI are outlined, as well as its current
      limitations.

PMID- 22158130
TI  - Advanced diffusion-weighted magnetic resonance imaging techniques of the human
      spinal cord.
AB  - Unlike those of the brain, advances in diffusion-weighted imaging (DWI) of the
      human spinal cord have been challenged by the more complicated and inhomogeneous
      anatomy of the spine, the differences in magnetic susceptibility between adjacent
      air and fluid-filled structures and the surrounding soft tissues, and the
      inherent limitations of the initially used echo-planar imaging techniques used to
      image the spine. Interval advances in DWI techniques for imaging the human spinal
      cord, with the specific aims of improving the diagnostic quality of the images,
      and the simultaneous reduction in unwanted artifacts have resulted in higher
      quality images that are now able to more accurately portray the complicated
      underlying anatomy and depict pathologic abnormality with improved sensitivity
      and specificity. Diffusion tensor imaging (DTI) has benefited from the advances
      in DWI techniques, as DWI images form the foundation for all tractography and
      DTI. This review provides a synopsis of the many recent advances in DWI of the
      human spinal cord, as well as some of the more common clinical uses for these
      techniques, including DTI and tractography.

PMID- 22158131
TI  - Mild traumatic brain injury: is diffusion imaging ready for primetime in forensic
      medicine?
AB  - Mild traumatic brain injury (MTBI) is difficult to accurately assess with
      conventional imaging because such approaches usually fail to detect any evidence
      of brain damage. Recent studies of MTBI patients using diffusion-weighted imaging
      and diffusion tensor imaging suggest that these techniques have the potential to
      help grade tissue damage severity, track its development, and provide prognostic
      markers for clinical outcome. Although these results are promising and indicate
      that the forensic diagnosis of MTBI might eventually benefit from the use of
      diffusion-weighted imaging and diffusion tensor imaging, healthy skepticism and
      caution should be exercised with regard to interpreting their meaning because
      there is no consensus about which methods of data analysis to use and very few
      investigations have been conducted, of which most have been small in sample size
      and examined patients at only one time point after injury.

PMID- 22158133
TI  - Chronic stress affects PERIOD2 expression through glycogen synthase kinase-3beta
      phosphorylation in the central clock.
AB  - Mood disorders are considered to be associated with altered circadian rhythms,
      but the correlation between them has remained obscure. The mood stabilizer,
      lithium, is an inhibitor of glycogen synthase kinase-3beta (GSK-3beta), which is
      a modulator of the circadian clock system. Here, we show that chronic restraint
      (CR) stress diminishes behavioral activity and rhythmicity in mice. CR stress
      elevated GSK-3beta phosphorylation and blunted the rhythmic expression of PERIOD2
      (PER2) in the brain. Moreover, lithium, when administered to the stress-imposed
      mice, reduced GSK-3beta phosphorylation and restored PER2 expression in the
      suprachiasmatic nucleus in a nighttime-specific manner. These data suggest that
      CR stress altered the circadian behavioral rhythm through a change in circadian
      gene expression of PER2 and GSK-3beta phosphorylation in the suprachiasmatic
      nucleus.

PMID- 22158134
TI  - Potential risk for healthy siblings to develop schizophrenia:  evidence from
      pattern classification with whole-brain connectivity.
AB  - Recent resting-state functional connectivity MRI studies using group-level
      statistical analysis have demonstrated the inheritable characters of
      schizophrenia. The objective of the present study was to use pattern
      classification as a means to investigate schizophrenia inheritance based on the
      whole-brain resting-state functional connectivity at the individual subject
      level. One-against-one pattern classifications were made amongst three groups
      (i.e. patients diagnosed with schizophrenia, healthy siblings, and healthy
      controls after preprocessing), resulting in an 80.4% separation between patients
      with schizophrenia and healthy controls, a 77.6% separation between schizophrenia
      patients and their healthy siblings, and a 78.7% separation between healthy
      siblings and healthy controls, respectively. These results suggest that the
      healthy siblings of schizophrenia patients have an altered resting-state
      functional connectivity pattern compared with healthy controls. Thus, healthy
      siblings may have a potential higher risk for developing schizophrenia compared
      with the general population. Moreover, this pattern differed from that of
      schizophrenia patients and may contribute to the normal behavior exhibition of
      healthy siblings in daily life.

PMID- 22158135
TI  - Morphological analysis of Drosophila larval peripheral sensory neuron dendrites
      and axons using genetic mosaics.
AB  - Nervous system development requires the correct specification of neuron position
      and identity, followed by accurate neuron class-specific dendritic development
      and axonal wiring. Recently the dendritic arborization (DA) sensory neurons of
      the Drosophila larval peripheral nervous system (PNS) have become powerful
      genetic models in which to elucidate both general and class-specific mechanisms
      of neuron differentiation. There are four main DA neuron classes (I-IV)(1). They
      are named in order of increasing dendrite arbor complexity, and have class
      specific differences in the genetic control of their differentiation(2-10). The
      DA sensory system is a practical model to investigate the molecular mechanisms
      behind the control of dendritic morphology(11-13) because: 1) it can take
      advantage of the powerful genetic tools available in the fruit fly, 2) the DA
      neuron dendrite arbor spreads out in only 2 dimensions beneath an optically clear
      larval cuticle making it easy to visualize with high resolution in vivo, 3) the
      class-specific diversity in dendritic morphology facilitates a comparative
      analysis to find key elements controlling the formation of simple vs. highly
      branched dendritic trees, and 4) dendritic arbor stereotypical shapes of
      different DA neurons facilitate morphometric statistical analyses. DA neuron
      activity modifies the output of a larval locomotion central pattern generator(14
      16). The different DA neuron classes have distinct sensory modalities, and their
      activation elicits different behavioral responses(14,16-20). Furthermore
      different classes send axonal projections stereotypically into the Drosophila
      larval central nervous system in the ventral nerve cord  (VNC)(21). These
      projections terminate with topographic representations of both DA neuron sensory
      modality and the position in the body wall of the dendritic field(7,22,23). Hence
      examination of DA axonal projections can be used to elucidate mechanisms
      underlying topographic mapping(7,22,23), as well as the wiring of a simple
      circuit modulating larval locomotion(14-17). We present here a practical guide to
      generate and analyze genetic mosaics(24) marking DA neurons via MARCM (Mosaic
      Analysis with a Repressible Cell Marker)(1,10,25) and Flp-out(22,26,27)
      techniques (summarized in Fig. 1).

PMID- 22158136
TI  - A new strategy for the implementation of an aerobic training session.
AB  - The objectives were to propose a new strategy for adjusting aerobic training
      variables based on the eighth American College of Sports Medicine (ACSM)
      guidelines and maximal aerobic power (&OV0312;O2max) and to establish energy
      expenditure (EE) recommendations for training, which depend on a subject's body
      mass (BM). Exclusively based on aerobic training recommendations that are
      available in the ACSM guidelines, 16 equally partitioned subcategories were
      created from the slope of a linear regression between the lower (16.4 ml.kg(
      1).min(-1)) and upper (61.2 ml.kg(-1).min(-1)) limits of VO(2max) percentile
      tables and all aerobic variables (intensity: 30-85%Reserve, duration: 60-300
      min.wk(-1), frequency: 3-5 d.wk(-1), and EE: 1,000-4,000 kcal.wk). ACSM's EE
      (EE(ACSM)) recommendation was compared to EE based on VO(2max) (EE(Actual)), BM,
      exercise intensity and duration combined, for five BM categories (60 to 100 kg).
      The following equations were generated to adjust aerobic training: Intensity
      (%(Reserve)) = VO(2max) (ml.kg(-1).min(-1)) * 1.23 + 9.85, Duration (min.wk(-1))
      = VO(2max) * 5.36-27.91, Frequency (d.wk(-1) = VO(2max) * 0.044 + 2.27, EE(ACSM)
      (kcal.wk(-1)) =VO(2max) * 82.61-1,055.29, and EE(Actual) (kcal.wk(-1)) =
      ([V(O2max) - 3.5] * Intensity + 3.5) * BM (kg)/200 * Frequency. A comparison of
      EE(ACSM) and EE(Actual) for 5 BM and 3 aerobic fitness categories demonstrated an
      effect size classification that is equal or superior to "large" in 9 of 15
      comparisons, suggesting that EE(ACSM) adjustment is inadequate at least 60% of
      the time. Despite the need to verify the adequacy of the linear model and perform
      future cross-sectional and longitudinal studies, the present proposal first
      provides criteria to adjust aerobic training variables consistent with subject
      capacity, thus diminishing the risk of the imprecise aerobic prescription.

PMID- 22158137
TI  - The effectiveness of resisted movement training on sprinting and jumping
      performance.
AB  - Resisted movement training is that in which the sports movement is performed with
      added resistance. To date, the effectiveness on enhancing sprint speed or
      vertical jump height had not been reviewed. The objectives of this review were to
      collate information on resisted training studies for sprinting and vertical
      jumping, ascertain whether resisted movement training was superior to normal
      unresisted movement training, and identify areas for future research. The review
      was based on peer-reviewed journal articles identified from electronic literature
      searches using MEDLINE and SPORTDiscus data bases from 1970 to 2010. Resisted
      sprint training was found to increase sprint speed but, in most cases, was no
      more effective than normal sprint training. There was some evidence that resisted
      sprint training was superior in increasing speed in the initial acceleration
      phase of sprinting. Resisted jump training in the form of weighted jump squats
      was shown to increase vertical jump height, but it was no more effective than
      plyometric depth jump training. Direct comparisons between resisted jump training
      and unresisted normal jump training were limited, but loaded eccentric
      countermovement jump squat training with unloaded concentric phase and eccentric
      landing was shown to generate superior results for elite jumpers. More
      prospective studies on resisted sprint training are required along with
      monitoring both kinematic and kinetic adaptations to fully determine any
      underlying mechanisms for any improvements in sprint speed. Based on the
      available data, the benefits and superiority of resisted sprint training have not
      been fully established. As for resisted jump training, although there are some
      promising findings, these results need to be duplicated by other researchers
      before resisted jump training can be claimed to be more effective than other
      forms of jump training.

PMID- 22158138
TI  - The effects of two bouts of high- and low-volume resistance exercise on glucose
      tolerance in normoglycemic women.
AB  - The purpose of the study was to determine the efficacy of a low-volume, moderate
      intensity bout of resistance exercise (RE) on glucose, insulin, and C-peptide
      responses during an oral glucose tolerance test (OGTT) in untrained women
      compared with a bout of high-volume RE of the same intensity. Ten women (age 30.1
      +/- 9.0 years) were assessed for body composition, maximal oxygen uptake, and 1
      repetition maximum (1RM) before completing 3 treatments administered in random
      order: 1 set of 10 REs (RE1), 3 sets of 10 REs (RE3), and no exercise (C). Twenty
      four hours after completing each treatment, an OGTT was performed after an
      overnight fast. Glucose area under the curve response to an OGTT was reduced
      after both RE1 (900 +/- 113 mmol.L(-1).min(-1), p = 0.056) and RE3 (827.9 +/-
      116.3, p = 0.01) compared with C (960.8 +/- 152.7 mmol.L(-1).min(-1)).
      Additionally, fasting glucose was significantly reduced after RE3 (4.48 +/- 0.45
      vs. 4.90 +/- 0.44 mmol.L(-1), p = 0.01). Insulin sensitivity (IS), as determined
      from the Cederholm IS index, was improved after RE1 (10.8%) and after RE3
      (26.1%). The reductions in insulin and C-peptide areas after RE1 and RE3 were not
      significantly different from those in the C treatment. In conclusion, greater
      benefits in glucose regulation appear to occur after higher volumes of RE.
      However, observed reductions in glucose, insulin, C-peptide areas after RE1
      suggest that individuals who may not well tolerate high-volume RE protocols may
      still benefit from low-volume RE at moderate intensity (65% 1RM).

PMID- 22158139
TI  - Effect of whole-body electromyostimulation on energy expenditure during exercise.
AB  - The application of whole-body electromyostimulation (WB-EMS) in the area of fat
      reduction and body shaping has become more popular recently. Indeed, some studies
      prove positive outcomes concerning parameters related to body composition.
      However, there are conflicting data as to whether EMS relevantly impacts energy
      expenditure (EE) during or after application. Thus, the main purpose of the study
      was to determine the acute effect of WB-EMS on EE. Nineteen moderately trained
      men (26.4 +/- 4.3 years) were randomly assigned to a typically used low-intensity
      resistance exercise protocol (16 minutes) with (85 Hz) and without WB-EMS. Using
      a crossover design, the same subjects performed both tests after completely
      recovering within 7 days. Energy expenditure as the primary endpoint of this
      study was determined by indirect calorimetry. The EE during low-intensity
      resistance exercise with adjuvant WB-EMS was significantly higher (p = 0.008)
      than that during the control condition (412 +/- 60 vs. 352 +/- 70 kcal; effect
      size; d = 0.92). This study clearly demonstrates the additive effect of WB-EMS on
      EE in moderately trained subjects during low-intensity resistance exercise
      training. Although this effect was statistically significant, the fast and
      significant reductions of body fat observed in recent studies suggest that the
      effect of WB-EMS on EE may still be underestimated by indirect calorimetry
      because of the inability of indirect calorimetry to accurately assess EE during
      "above-steady state conditions." Although from a statistically point of view WB
      EMS clearly impacts EE, the relatively small effect did not suggest a broad
      application of this device in this area. However, taking other positive outcomes
      of this technology into account, WB-EMS may be a time-saving option at least for
      subjects unwilling or unable to exercise conventionally.

PMID- 22158140
TI  - Criterion and longitudinal validity of a fixed-distance incremental running test
      for the determination of lactate thresholds in field settings.
AB  - The aim of this study was to examine the criterion validity of 2 lactate
      thresholds (LTs, intensity corresponding to 1 mmol.L(-1) above baseline; onset of
      blood lactate accumulation, intensity at 4 mmol.L(-1)) determined with a fixed
      distance incremental field test by assessing their correlation with those
      obtained using a traditional fixed-time laboratory protocol. A second aim was to
      verify the longitudinal validity by examining the relationships between the
      changes in LTs obtained with the 2 protocols. To determine the LTs, 12 well
      trained male middle and long distance amateur and competitive runners training
      from 4 to 7 d.wk(-1) (age 25 [5] years, body mass 66 [5] kg, estimated VO(2)max
      58.6 [4.9] ml.min(-1).kg(-1), SD in parentheses) performed in 2 separate sessions
      an incremental running test on the field starting at 12 km.h(-1) and increasing
      the speed by 1 km.h(-1) every 1,200 m (FixD test) and an incremental treadmill
      test in the laboratory starting at 12 km.h(-1) and increasing the speed by 1
      km.h(-1) every 6 minutes. The 2 tests were repeated after 6-12 weeks. A nearly
      perfect relationship was found between the running speeds at LTs determined with
      the 2 protocols (r = 0.95 [CI95% 0.83-0.99]; p < 0.001). The correlations between
      longitudinal changes in LTs were very large (0.78 [0.32-0.95; p = 0.006]). The
      heart rate corresponding to the LTs were not significantly different. This study
      showed the criterion and longitudinal validity of LTs determined with a protocol
      consisting of fixed-distance intervals performed in field setting.

PMID- 22158141
TI  - The effect of aerobic exercise during the interset rest periods on kinematics,
      kinetics, and lactate clearance of two resistance loading schemes.
AB  - It may be possible to enhance set and session kinematics and kinetics by engaging
      in low-intensity aerobic exercise during the interset rest period. The purpose of
      this study therefore was to quantify the change in session kinematics and
      kinetics of 35% 1RM and 70% 1RM loading schemes equated by volume, when aerobic
      exercise or passive rest was undertaken between sets. Twelve male student
      athletes were recruited for this study. Squat average force, peak force, average
      power, peak power, total work, and total impulse were quantified using a force
      plate and linear transducer. Blood lactate samples were taken before set 1, after
      set 1, after set 2, and after the last set performed. No significant (p < 0.05)
      differences (0.37-9.24%) were found in any of the kinematic and kinetic variables
      of interset after active or passive interset rest periods. Significant increases
      (64-76%) in blood lactate occurred from the inception of exercise to completion,
      for both the heavy and light loading schemes. However, no significant differences
      in lactate accumulation were noted, whether active or passive recovery was
      undertaken in the interest rest period. It was concluded that active recovery in
      the form of low-intensity cycling offered no additional benefits in terms of
      lactate clearance and enhancement of set and session kinematics and kinetics.

PMID- 22158142
TI  - The effect of training volume on lower-body strength.
AB  - The objective of this study was to examine the chronic effects on lower-body
      strength in resistance trained men of performing varying training volumes over 6
      weeks. A pretest and posttest design was used to investigate the effects on 1
      repetition maximum (1RM) squat strength. Also, 1RM testing was performed at 3
      weeks. Participants were randomly assigned to an intensity-matched (80% of 1RM)
      low (1-SET), moderate (4-SET), or high (8-SET) volume condition. In addition to
      significant strength increases in all groups at the end of the 6-week period,
      increases were observed at 3 weeks under the 4- and 8-SET conditions, which were
      greater than the improvement under the 1-SET condition. At 6 weeks, the magnitude
      of improvement was significantly greater for the 8-SET, as compared with that of
      the 1-SET group. The magnitude of improvement elicited in the 4-SET group was not
      different from that of the 1-SET or 8-SET groups. The results suggest that "high"
      volumes (i.e., >4 sets) are associated with enhanced strength development but
      that "moderate" volumes offer no advantage. Practitioners should be aware that
      strength development may be dependent on appropriate volume doses and training
      duration.

PMID- 22158143
TI  - Acute effects of whole-body vibration on neuromuscular responses in older
      individuals: implications for prescription of vibratory stimulation.
AB  - The aim of this study was to analyze surface electromyography activity (sEMG) and
      rating of perceived exertion (RPE) responses in different muscles while standing
      on a vibrating platform producing oscillations of different frequencies and
      amplitudes. Twenty community-dwelling older adults (79.6 +/- 3.2 years) took part
      in the research. Subjects were exposed to 12 different vibration treatments of 15
      seconds separated by 1 minute of rest in random order to check the influence of
      frequency (25, 35, and 45 Hz) and amplitude (1 mm [low] and 3.1 mm [high])
      vibration on sEMG signal and RPE. Additionally, the use of a soft pad was also
      examined for its influence on these measures. Three-factor analysis of variance
      for RPE and both lower and whole-body sEMGs revealed a significant amplitude main
      effect (p < 0.01), and soft mat effect (p < 0.01), and a significant frequency
      main effect (p < 0.01). The major findings were that sEMG and RPE increased with
      the acceleration of the vibration; moreover, the increments of sEMG were highly
      correlated with RPE. The results of this study suggest that using the RPE method
      after each exercise would allow exercise and health professionals to assess the
      intensity levels that correspond to the level of the vibratory program in older
      adults.

PMID- 22158144
TI  - Sprinting patterns of National Rugby League competition.
AB  - The purpose of this study was to investigate the sprinting demands of National
      Rugby League (NRL) competition and characterize the sprinting patterns of
      different rugby league playing positions. Thirty-seven elite rugby league players
      (mean +/- SE age: 23.6 +/- 0.5 years) underwent global positioning satellite
      analysis during 104 NRL appearances. The majority (67.5%) of sprint efforts were
      across distances of <20 m. The most common sprint distance for hit-up forwards
      was 6-10 m (46.3%). Outside backs had a greater proportion (33.7%) of sprint
      efforts over distances of >=21 m. The proportion of sprint efforts over 40 m or
      greater for hit-up forwards, wide running forwards, adjustables, and outside
      backs was 5.0, 7.4, 5.0, and 9.7%, respectively. Of the sprints performed,
      approximately 48.0% involved contact, approximately 58.0% were preceded by
      forward locomotion (forward walking, jogging, or striding), whereas over 24.0%
      occurred from a standing start. Hit-up forwards more commonly sprinted from a
      standing start, or after lateral movement, whereas forward striding activities
      more commonly preceded sprint efforts for the adjustables and outside backs. The
      majority of sprint efforts were performed without the ball (78.7 vs. 21.3%). Most
      sprint efforts (67.5%) were followed by a long recovery (i.e., >=5 minutes).
      Outside backs had the greatest proportion (76.1%) of long duration recovery
      periods and the smallest proportion (1.8%) of short duration recovery periods
      (i.e., <60 seconds) between sprints. The results of this study demonstrate
      differences among rugby league playing positions for the nature of sprint efforts
      and the typical distances covered during these efforts. Furthermore, the
      activities preceding and the recovery periods after sprint efforts were different
      among playing positions. These findings suggest that rugby league sprint training
      should be tailored to meet the individual demands of specific playing positions.

PMID- 22158146
TI  - Difference in kinematics and kinetics between high- and low-velocity resistance
      loading equated by volume: implications for hypertrophy training.
AB  - Although it is generally accepted that a high load is necessary for muscle
      hypertrophy, it is possible that a low load with a high velocity results in
      greater kinematics and kinetics than does a high load with a slow velocity. The
      purpose of this study was to determine if 2 training loads (35 and 70% 1
      repetition maximum [1RM]) equated by volume, differed in terms of their session
      kinematic and kinetic characteristics. Twelve subjects were recruited in this
      acute randomized within-subject crossover design study. Two bouts of a half-squat
      exercise were performed 1 week apart, one with high load-low velocity (HLLV = 3
      sets of 12 reps at 70% 1RM) and the other with low-load high-velocity (LLHV = 6
      sets of 12 reps at 35% 1RM). Time under tension (TUT), average force, peak force
      (PF), average power (AP), peak power (PP), work (TW), and total impulse (TI) were
      calculated and compared between loads for the eccentric and concentric phases.
      For average eccentric and concentric single repetition values, significantly (p <
      0.05) greater (~15-22%) PP outputs were associated with the LLHV loading, whereas
      significantly greater (~7-61%) values were associated with the HLLV condition for
      most other variables of interest. However, in terms of total session kinematics
      and kinetics, the LLHV protocol resulted in significantly greater (~16-61%)
      eccentric and concentric TUT, PF, AP, PP, and TW. The only variable that was
      significantly greater for the HLLV protocol than for the LLHV protocol was TI
      (~20-24%). From these results, it seems that the LLHV protocol may offer an equal
      if not better training stimulus for muscular adaptation than the HLLV protocol,
      because of the greater time under tension, power, force, and work output when the
      total volume of the exercise is equated.

PMID- 22158147
TI  - A pilot study to evaluate the effects of vardenafil on sexual distress in men
      with obesity.
AB  - There are no interventional studies on the impact of sexual distress (SD) in men
      with obesity. We investigated the effects of vardenafil (VAR) on SD in middle
      aged (mean age 49 +/- 8), healthy, obese men in the absence of premature
      ejaculation, ED or hypogonadism. After a 4-week run-in period, 20 men with high
      body mass index (BMI=40 +/- 8) and SD at the Sexual Distress Esteem Questionnaire
      Male (mean score 65 +/- 20 AU) were randomized to receive either VAR 10 mg on
      demand (N=10) or matched-placebo (PLB, N=10). Primary endpoints were variations
      from baseline in the intravaginal ejaculatory latency time (IELT) measured by the
      stopwatch technique; secondary endpoints were variations from baseline in Self
      Esteem and Relationship (SEAR) and Male Sexual Health Questionnaire-Ejaculatory
      domain (MSHQ-EjD) scores. VAR significantly improved IELT (P<0.0001), as well as
      SEAR (P<0.001) and MSHQ-EjD (P<0.005) scores, whereas no changes were observed
      after PLB. Interestingly, an inverse relationship between BMI and IELT was found
      in all the men studied (r(2)=0.37, P<0.001). SD in healthy obese men seems to be
      correlated mainly with inadequate ejaculatory control, especially in men with
      higher BMI. Our preliminary results suggest that treatment with VAR may improve
      ejaculatory control, thus ameliorating self-esteem and sexual performance in men
      with obesity.

PMID- 22158148
TI  - The ethics of cosmetics.

PMID- 22158149
TI  - NHS astonishment.

PMID- 22158150
TI  - RVG glove.

PMID- 22158151
TI  - Calling disabled dentists.

PMID- 22158152
TI  - Does it work?

PMID- 22158153
TI  - Well equipped patients.

PMID- 22158154
TI  - An advised choice.

PMID- 22158155
TI  - Disease risk.

PMID- 22158157
TI  - Fixed braces are best and cheapest.

PMID- 22158167
TI  - An effective oral health promoting message?
AB  - This paper questions the effectiveness of current oral health promoting
      activities in reducing social inequalities in oral health. An attempt is made to
      address the needs of dental professionals and nutritionists in communicating an
      understanding of biological aspects of the aetiology of caries and erosion. With
      a clear understanding of the disease process oral health promoters can possibly
      reduce social inequalities in oral health. A clear common message which satisfies
      both dental and nutritional professionals is presented. The issues of commonality
      and ambiguity are fundamental to effective behavioural/teaching practice.
      Currently the evidence base suggests that dietary messages are inconsistent and
      ambiguous. Therefore, a clear common and unambiguous dietary message, based on
      science, could go some way to improving oral health inequalities.

PMID- 22158168
TI  - Contemporary endodontics - part 2.
AB  - The aim of this paper is to present the contemporary developments in root canal
      treatment, restoration of the endodontically treated tooth, and advanced
      endodontic procedures, such as root canal retreatment and surgical endodontics.

PMID- 22158173
TI  - Summary of: Introducing care pathway commissioning to primary dental care:
      measuring performance.

PMID- 22158174
TI  - Summary of: Factors influencing the shade matching performance of dentists and
      dental technicians when using two different shade guides.

PMID- 22158175
TI  - Current trends in removable partial denture teaching in British dental schools.
AB  - AIM: To investigate current teaching of removable partial denture construction in
      British dental schools. MATERIALS AND METHOD: A questionnaire was sent by email
      to each of the 15 UK dental schools. RESULTS: Replies were received from the 12
      long established schools, although one declined to participate. The more recently
      established schools did not respond. All schools have a pre-clinical/technical
      course, which either precedes or runs in parallel with the early part of the
      students' partial denture experience, but students complete very little, if any
      technical work for their clinical cases. The majority of teaching takes place in
      multidisciplinary teaching clinics in years 2-5 although the majority of schools
      concentrate teaching of the basics early in the programme. Fewer cases appear to
      be treated than previously reported, especially cases requiring removable partial
      dentures with cobalt chromium frameworks. Students may only treat one such case,
      the remainder of dentures being constructed of acrylic resin. Lack of experience
      treating cases requiring a combination of complete and removable partial dentures
      was a concern. CONCLUSION: Participating schools appear to meet the General
      Dental Council's requirements. The amount of clinical work undertaken by students
      may have decreased slightly. There has been a greater decrease in the technical
      component.

PMID- 22158196
TI  - Introducing care pathway commissioning to primary dental care: measuring
      performance.
AB  - Care pathways have been used in a variety of ways: firstly to support quality
      improvement through standardising clinical processes, but also for secondary
      purposes, by purchasers of healthcare, to monitor activity and health outcomes
      and to commission services. This paper focuses on reporting a secondary use of
      care pathways: to commission and monitor performance of primary dental care
      services. Findings of a project involving three dental practices implementing a
      system based on rating patients according to their risk of disease and need for
      care are outlined. Data from surgery-based clinical databases and interviews from
      commissioners and providers are reported. The use of both process and outcome key
      performance indicators in this context is discussed, as well as issues which
      arise such as attributability of outcome measures and strategic approaches to
      improving quality of care.

PMID- 22158197
TI  - Factors influencing the shade matching performance of dentists and dental
      technicians when using two different shade guides.
AB  - INTRODUCTION: In recent years increased patient aesthetic expectations have
      brought about closer scrutiny of shade taking and communication processes with
      the aim of increasing the chances of success of obtaining good indirect
      restoration appearance. When shade matching, the most popular approach is to
      match the shade of the natural dentition using a shade guide to specify the shade
      of the final restoration before fabrication. A recent alternative approach is to
      also specify the shade of the tooth preparation to facilitate its replication in
      the die upon which the restoration will be made. OBJECTIVE: To assess (1) the
      colour vision ability of a sample of dentists and dental technicians and
      correlate this to their shade matching performance in a simulated clinical
      situation, and (2) the accuracy and reproducibility of shade matches using two
      shade guides. DESIGN: In vitro study. METHOD: Consenting dentists and dental
      technicians within Dundee Dental School and Hospital undertook a Farnsworth
      Munsell 100 (FM-100) Hue test and matched (on two separate occasions) the shades
      of six prepared extracted teeth, containing either a veneer or crown preparation,
      using both the IPS Natural Die Material shade guide (Ivoclar Vivadent) (IPS) and
      the Vitapan Classical shade guide (VITA Zahnfabrik) (VC). RESULTS: Eighteen
      dental technicians (16 males and 2 females) and 40 dentists (21 males and 19
      females) completed the study. The raw data revealed that many subjects were
      inconsistent in their approach to shade matching. The IPS guide afforded greater
      reproducibility. No significant effects (p >0.05) of subject gender and age upon
      overall shade matching performance were demonstrated. Performance in the FM-100
      Hue test did not statistically affect (p >0.05) the outcome of matching using the
      guides. CONCLUSIONS: Within the limitations of this study, (a) the FM-100 Hue
      test was not a good predictor of dental shade matching performance, and (b) both
      guides performed well in the areas of shade they covered, with the Vita Classical
      guide matching well shades of natural unstained teeth and the IPS guide matching
      more closely stained/discoloured preparations.

PMID- 22158198
TI  - Neuroendocrinology: Improved progression-free survival with everolimus plus
      octreotide in carcinoid syndrome.

PMID- 22158199
TI  - Adrenal gland: New dual-release hydrocortisone tablet for adrenal insufficiency.

PMID- 22158200
TI  - Primary aldosteronism in 2011: Towards a better understanding of causation and
      consequences.
AB  - With primary aldosteronism now widely acknowledged as common and associated with
      both hypertension-related and non-hypertension-related pathology, research
      interest into its causes and consequences continues to grow. In 2011, major
      breakthroughs occurred in understanding the role and nature of underlying genetic
      disturbances and elucidating the pathophysiology of its cardiovascular sequelae.

PMID- 22158202
TI  - Troubled waters.

PMID- 22158203
TI  - The press under pressure.

PMID- 22158204
TI  - A massive comfort.

PMID- 22158205
TI  - If you want to win the game, you must join in.

PMID- 22158216
TI  - Cutbacks threaten HIV gains.

PMID- 22158217
TI  - Nano rules fall foul of data gap.

PMID- 22158219
TI  - Dynamo maker ready to roll.

PMID- 22158218
TI  - Novartis to shut brain research facility.

PMID- 22158220
TI  - State cuts fuel California protests.

PMID- 22158221
TI  - Ocean conservation: Uncertain sanctuary.

PMID- 22158223
TI  - Technology: Asia's space race.

PMID- 22158222
TI  - Out-of-body experience: Master of illusion.

PMID- 22158224
TI  - Social science: Open up online research.

PMID- 22158229
TI  - Scientific fraud: Europe must address research misconduct.

PMID- 22158230
TI  - Behavioural biology: Canny liars score by tricking themselves.

PMID- 22158231
TI  - Violence: Intuition is important too.

PMID- 22158232
TI  - Military intelligence: Caution over Iran's nuclear plans.

PMID- 22158233
TI  - Violence: The role of society and state.

PMID- 22158235
TI  - Norman Ramsey (1915-2011).

PMID- 22158236
TI  - Organic chemistry: A radical approach to diversity.

PMID- 22158237
TI  - Stem cells: The clock within.

PMID- 22158238
TI  - Astrophysics: Monster black holes.

PMID- 22158239
TI  - Genetics: Noise rules.

PMID- 22158240
TI  - Materials science: A sense for touch.

PMID- 22158241
TI  - Cancer: Sacrifice for survival.

PMID- 22158243
TI  - Assembly of hybrid photonic architectures from nanophotonic constituents.
AB  - The assembly of hybrid nanophotonic devices from different fundamental photonic
      entities--such as single molecules, nanocrystals, semiconductor quantum dots,
      nanowires and metal nanoparticles--can yield functionalities that exceed those of
      the individual subunits. Combining these photonic elements requires nanometre
      scale fabrication precision and potentially involves a material diversity that is
      incompatible with standard nanotechnological processes. Although merging these
      different systems on a single hybrid platform is at present challenging, it
      promises improved performance and novel devices. Particularly rapid progress is
      seen in the combination of plasmonic-dielectric constituents with quantum
      emitters that can be assembled on demand into fundamental model systems for
      future optical elements.

PMID- 22158244
TI  - Two ten-billion-solar-mass black holes at the centres of giant elliptical
      galaxies.
AB  - Observational work conducted over the past few decades indicates that all massive
      galaxies have supermassive black holes at their centres. Although the
      luminosities and brightness fluctuations of quasars in the early Universe suggest
      that some were powered by black holes with masses greater than 10 billion solar
      masses, the remnants of these objects have not been found in the nearby Universe.
      The giant elliptical galaxy Messier 87 hosts the hitherto most massive known
      black hole, which has a mass of 6.3 billion solar masses. Here we report that NGC
      3842, the brightest galaxy in a cluster at a distance from Earth of 98
      megaparsecs, has a central black hole with a mass of 9.7 billion solar masses,
      and that a black hole of comparable or greater mass is present in NGC 4889, the
      brightest galaxy in the Coma cluster (at a distance of 103 megaparsecs). These
      two black holes are significantly more massive than predicted by linearly
      extrapolating the widely used correlations between black-hole mass and the
      stellar velocity dispersion or bulge luminosity of the host galaxy. Although
      these correlations remain useful for predicting black-hole masses in less massive
      elliptical galaxies, our measurements suggest that different evolutionary
      processes influence the growth of the largest galaxies and their black holes.

PMID- 22158245
TI  - Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis.
AB  - Modern drug discovery relies on the continual development of synthetic
      methodology to address the many challenges associated with the design of new
      pharmaceutical agents. One such challenge arises from the enzymatic metabolism of
      drugs in vivo by cytochrome P450 oxidases, which use single-electron oxidative
      mechanisms to rapidly modify small molecules to facilitate their excretion. A
      commonly used synthetic strategy to protect against in vivo metabolism involves
      the incorporation of electron-withdrawing functionality, such as the
      trifluoromethyl (CF(3)) group, into drug candidates. The CF(3) group enjoys a
      privileged role in the realm of medicinal chemistry because its incorporation
      into small molecules often enhances efficacy by promoting electrostatic
      interactions with targets, improving cellular membrane permeability, and
      increasing robustness towards oxidative metabolism of the drug. Although common
      pharmacophores often bear CF(3) motifs in an aromatic system, access to such
      analogues typically requires the incorporation of the CF(3) group, or a surrogate
      moiety, at the start of a multi-step synthetic sequence. Here we report a mild,
      operationally simple strategy for the direct trifluoromethylation of unactivated
      arenes and heteroarenes through a radical-mediated mechanism using commercial
      photocatalysts and a household light bulb. We demonstrate the broad utility of
      this transformation through addition of CF(3) to a number of heteroaromatic and
      aromatic systems. The benefit to medicinal chemistry and applicability to late
      stage drug development is also shown through examples of the direct
      trifluoromethylation of widely prescribed pharmaceutical agents.

PMID- 22158246
TI  - Combined obliquity and precession pacing of late Pleistocene deglaciations.
AB  - Milankovitch proposed that Earth resides in an interglacial state when its spin
      axis both tilts to a high obliquity and precesses to align the Northern
      Hemisphere summer with Earth's nearest approach to the Sun. This general concept
      has been elaborated into hypotheses that precession, obliquity or combinations of
      both could pace deglaciations during the late Pleistocene. Earlier tests have
      shown that obliquity paces the late Pleistocene glacial cycles but have been
      inconclusive with regard to precession, whose shorter period of about 20,000
      years makes phasing more sensitive to timing errors. No quantitative test has
      provided firm evidence for a dual effect. Here I show that both obliquity and
      precession pace late Pleistocene glacial cycles. Deficiencies in time control
      that have long stymied efforts to establish orbital effects on deglaciation are
      overcome using a new statistical test that focuses on maxima in orbital forcing.
      The results are fully consistent with Milankovitch's proposal but also admit the
      possibility that long Southern Hemisphere summers contribute to deglaciation.

PMID- 22158247
TI  - Acute vision in the giant Cambrian predator Anomalocaris and the origin of
      compound eyes.
AB  - Until recently, intricate details of the optical design of non-biomineralized
      arthropod eyes remained elusive in Cambrian Burgess-Shale-type deposits, despite
      exceptional preservation of soft-part anatomy in such Konservat-Lagerstatten. The
      structure and development of ommatidia in arthropod compound eyes support a
      single origin some time before the latest common ancestor of crown-group
      arthropods, but the appearance of compound eyes in the arthropod stem group has
      been poorly constrained in the absence of adequate fossils. Here we report 2-3-cm
      paired eyes from the early Cambrian (approximately 515 million years old) Emu Bay
      Shale of South Australia, assigned to the Cambrian apex predator Anomalocaris.
      Their preserved visual surfaces are composed of at least 16,000 hexagonally
      packed ommatidial lenses (in a single eye), rivalling the most acute compound
      eyes in modern arthropods. The specimens show two distinct taphonomic modes,
      preserved as iron oxide (after pyrite) and calcium phosphate, demonstrating that
      disparate styles of early diagenetic mineralization can replicate the same type
      of extracellular tissue (that is, cuticle) within a single Burgess-Shale-type
      deposit. These fossils also provide compelling evidence for the arthropod
      affinities of anomalocaridids, push the origin of compound eyes deeper down the
      arthropod stem lineage, and indicate that the compound eye evolved before such
      features as a hardened exoskeleton. The inferred acuity of the anomalocaridid eye
      is consistent with other evidence that these animals were highly mobile visual
      predators in the water column. The existence of large, macrophagous nektonic
      predators possessing sharp vision--such as Anomalocaris--within the early
      Cambrian ecosystem probably helped to accelerate the escalatory 'arms race' that
      began over half a billion years ago.

PMID- 22158248
TI  - Predicting mutation outcome from early stochastic variation in genetic
      interaction partners.
AB  - Many mutations, including those that cause disease, only have a detrimental
      effect in a subset of individuals. The reasons for this are usually unknown, but
      may include additional genetic variation and environmental risk factors. However,
      phenotypic discordance remains even in the absence of genetic variation, for
      example between monozygotic twins, and incomplete penetrance of mutations is
      frequent in isogenic model organisms in homogeneous environments. Here we propose
      a model for incomplete penetrance based on genetic interaction networks. Using
      Caenorhabditis elegans as a model system, we identify two compensation mechanisms
      that vary among individuals and influence mutation outcome. First, feedback
      induction of an ancestral gene duplicate differs across individuals, with high
      expression masking the effects of a mutation. This supports the hypothesis that
      redundancy is maintained in genomes to buffer stochastic developmental failure.
      Second, during normal embryonic development we find that there is substantial
      variation in the induction of molecular chaperones such as Hsp90 (DAF-21).
      Chaperones act as promiscuous buffers of genetic variation, and embryos with
      stronger induction of Hsp90 are less likely to be affected by an inherited
      mutation. Simultaneously quantifying the variation in these two independent
      responses allows the phenotypic outcome of a mutation to be more accurately
      predicted in individuals. Our model and methodology provide a framework for
      dissecting the causes of incomplete penetrance. Further, the results establish
      that inter-individual variation in both specific and more general buffering
      systems combine to determine the outcome inherited mutations in each individual.

PMID- 22158250
TI  - GSK-3alpha/beta kinases and amyloid production in vivo.
AB  - Arising from C. J. Phiel, C. A. Wilson, V. M.-Y. Lee & P. S. Klein  423, 435-439
      (2003)A major unresolved issue in Alzheimer's disease is identifying the
      mechanisms that regulate proteolytic processing of amyloid precursor protein
      (APP)-glycogen synthase kinase-3 (GSK-3) isozymes are thought to be important in
      this regulation. Phiel et al. proposed that GSK-3alpha, but not GSK-3beta,
      controls production of amyloid. We analysed the proteolytic processing of mouse
      and human APP in mouse brain in vivo in five different genetic and viral models.
      Our data do not yield evidence for either GSK-3alpha-mediated or GSK-3beta
      mediated control of APP processing in brain in vivo.

PMID- 22158252
TI  - Resolution of SPAM following cordectomy: implications for understanding
      pathophysiology.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe the clinical benefit of a
      spinal cordectomy with the aim of limiting neurological deterioration related to
      the development of a subacute posttraumatic ascending myelopathy (SPAM)
      supporting previously described mechanism for SPAM formation. SETTING: National
      Spinal Injuries Centre, Stoke Mandeville Hospital, UK. METHOD AND RESULTS: A 38
      year old patient presented 6 months after spinal cord injury substantial
      neurological deterioration expanding from the initial T4-injury level through C4.
      Magnetic resonance imaging revealed intra-medullary haemorrhage at the site of
      injury and subsequent-ascending cord oedema. A cordectomy was performed leading
      to neurological stabilisation and complete resolution of SPAM. CONCLUSION:
      Cordectomy can be an effective intervention in case of rapid progressive
      neurological deterioration.

PMID- 22158253
TI  - Spinal cord injury and physical activity: preservation of the body.
AB  - SETTING: Spinal cord injury (SCI) causes devastating loss of function and can
      result in serious secondary complications. Although significant advances are
      being made to develop cellular and molecular therapies to promote regeneration,
      it is important to optimize physical interventions. OBJECTIVES: The objective of
      this review was to examine the evidence for the effects of physical
      rehabilitation strategies on health and fitness, and maintenance of target
      systems below the level of injury (for example, muscle, bone, circulation).
      RESULTS: Exercise appears to be a potent means of achieving these goals, using a
      variety of strategies. CONCLUSION: Physical rehabilitation after SCI needs to
      move beyond the goal of maximizing independence to focus on maintenance of
      optimum health and fitness as well as maintenance of target system function below
      the level of injury. Issues requiring further investigation include
      identification of the optimum dosage of interventions to achieve specific goals,
      for example, prevention of muscle atrophy and osteoporosis, and development and
      validation of simple clinical measures to monitor the changes in body
      composition. Adoption of a classification system for physical interventions and
      standardized outcome measures would facilitate large-scale observational studies
      to identify the critical variables contributing to better outcomes.

PMID- 22158254
TI  - Response to 'The administration of high-dose methylprednisolone for 24 h reduced
      muscle size and increased atrophy-related gene expression in spinal cord-injured
      rats'.

PMID- 22158255
TI  - The prevalence of pulmonary embolism in chronically paralyzed subjects: a review
      of available evidence.
AB  - STUDY DESIGN: Qualitative systematic review. OBJECTIVES: To examine the validity
      of the prevailing notion that pulmonary embolism (PE) is rare in the chronic
      spinal cord injury (SCI) population. SETTING: USA. METHODS: Review surveys of
      adult SCI subjects >2 months after injury in which PE has been looked for and its
      prevalence estimated. RESULTS: A total of 16 surveys of chronic SCI subjects
      published between 1956 and 2009 offered data on PE prevalence. Two autopsy
      surveys, 178 subjects paralyzed >2 months, revealed no PE. Eleven surveys of the
      cause of death, 3193 subjects paralyzed 1-25 years, revealed PE in 2.1%. Two
      surveys of survivors of SCI, 5761 subjects paralyzed 1-25 years, revealed PE in
      0.4%. Our survey of 112 subjects paralyzed 1-50 years before death, revealed PE
      in 21 (18.7%), based on autopsy, imaging, clinical and electrocardiographic
      evidence. In 7 (33%) of the 21 subjects with PE, pulmonary hypertension by
      transthoracic echocardiography was detected, indicating recurrent and/or
      unresolved PE. CONCLUSION: PE is not infrequent in the chronic SCI subject; but
      its presentation may be subclinical; and its apparent recurrence may lead to
      pulmonary hypertension.

PMID- 22158256
TI  - Teratoma generation in the testis capsule.
AB  - Pluripotent stem cells (PSCs) have the unique characteristic that they can
      differentiate into cells from all three germ layers.  This makes them a
      potentially valuable tool for the treatment of many different diseases.  With the
      advent of induced pluripotent stem cells (iPSCs) and continuing research with
      human embryonic stem cells (hESCs) there is a need for assays that can
      demonstrate that a particular cell line is pluripotent.  Germline transmission
      has been the gold standard for demonstrating the pluripotence of mouse embryonic
      stem cell (mESC) lines(1,2,3).   Using this assay, researchers can show that a
      mESC line can make all cell types in the embryo including germ cells(4).  With
      the generation of human ESC lines(5,6), the appropriate assay to prove
      pluripotence of these cells was unclear since human ESCs cannot be tested for
      germline transmission.  As a surrogate, the teratoma assay is currently used to
      demonstrate the pluripotency of human pluripotent stem cells (hPSCs)(7,8,9).
      Though this assay has recently come under scrutiny and new technologies are being
      actively explored, the teratoma assay is the current gold standard(7).  In this
      assay, the cells in question are injected into an immune compromised mouse.  If
      the cells are pluripotent, a teratoma will eventually develop and sections of the
      tumor will show tissues from all 3 germ layers(10).  In the teratoma assay, hPSCs
      can be injected into different areas of the mouse.  The most common injection
      sites include the testis capsule, the kidney capsule, the liver; or into the leg
      either subcutaneously or intramuscularly(11).  Here we describe a robust protocol
      for the generation of teratomas from hPSCs using the testis capsule as the site
      for tumor growth.

PMID- 22158257
TI  - An examination of preactivity and postactivity flexibility practices of National
      Collegiate Athletic Association Division I tennis coaches.
AB  - The purpose of this study was to determine if National Collegiate Athletic
      Association (NCAA) Division I men's tennis programs are in compliance with
      suggested current preactivity and postactivity stretching protocols.
      Questionnaires were sent to NCAA Division I men's tennis programs in the USA.
      Seventy-six coaches (73 men and 3 women) participated in the study. The results
      of the Chi-Square analysis suggest that the number of years of head coaching
      experience had a significant relationship with the preactivity stretching
      routines employed by coaches (p = 0.029). A significant difference was found
      between preactivity stretching routines and the key sources of influence for the
      foundation of knowledge regarding preactivity stretching (p = 0.012). Some
      results indicate that many tennis coaches do not use current suggested practices
      for preactivity stretching. The results of this study indicate that certification
      may influence how well research guidelines are followed. Further research is
      needed to delineate how these factors affect coaching decisions.

PMID- 22158258
TI  - Associations of muscular fitness with psychological positive health, health
      complaints, and health risk behaviors in Spanish children and adolescents.
AB  - We examined the association of muscular fitness with psychological positive
      health, health complaints, and health risk behaviors in 690 (n = 322 girls)
      Spanish children and adolescents (6-17.9 years old). Lower body muscular strength
      was assessed with the standing long jump test, and upper-body muscular strength
      was assessed with the throw basketball test. A muscular fitness index was
      computed by means of standardized measures of both tests. Psychosocial positive
      health, health complaints, and health risk behaviors were self-reported using the
      items of the Health Behavior in School-aged Children questionnaire. Psychological
      positive health indicators included the following: perceived health status, life
      satisfaction, quality of family relationships, quality of peer relationships, and
      academic performance. We computed a health complaints index from 8 registered
      symptoms: headache, stomach ache, backache, feeling low, irritability or bad
      temper, feeling nervous, difficulties getting to sleep, and feeling dizzy. The
      health risk behavior indicators studied included tobacco use, alcohol use, and
      getting drunk. Children and adolescents with low muscular fitness (below the
      mean) had a higher odds ratio (OR) of reporting fair (vs. excellent) perceived
      health status, low life satisfaction (vs. very happy), low quality of family
      relationships (vs. very good), and low academic performance (vs. very good).
      Likewise, children and adolescents having low muscular fitness had a
      significantly higher OR of reporting smoking tobacco sometimes (vs. never),
      drinking alcohol sometimes (vs. never), and getting drunk sometimes (vs. never).
      The results of this study suggest a link between muscular fitness and
      psychological positive health and health risk behavior indicators in children and
      adolescents.

PMID- 22158259
TI  - The effect of a traditional dance training program on dynamic balance of
      individuals with mental retardation.
AB  - The purpose of this study was to evaluate the influence of a Greek traditional
      dance training program on the dynamic balance of individuals with mental
      retardation (MR). A total of 17 individuals participated in this study. Ten
      individuals with mild or moderate MR and 7 individuals with mild or moderate MR
      who studied in special schools were assigned to intervention (MR-I) and control
      (MR-C) groups, respectively. Pretraining and posttraining exercise tests were
      performed to determine the dynamic balance ability. Dynamic balance ability was
      measured by means of a balance deck (Lafayette, Lafayette, IN, USA) in 30-, 45-,
      and 60-second intervals. The MR-I group underwent a 16-week Greek traditional
      dance training program at a frequency of 3 times per week and for a duration of
      45 minutes per season. Posttraining results showed that the individuals with MR
      in the MR-I group improved during treatment, from their baseline scores on
      dynamic balance measurements (30 seconds: p < 0.01, 45 seconds: p < 0.05, 60
      seconds: p < 0.05). The MR-C group did not show any improvement between the 2
      measurements. In conclusion, individuals with MR may be able to improve their
      dynamic balance when performing a systematic and well-designed Greek traditional
      dance training program.

PMID- 22158260
TI  - The effect of warm-ups incorporating different volumes of dynamic stretching on
      10- and 20-m sprint performance in highly trained male athletes.
AB  - Recently, athletes have transitioned from traditional static stretching during
      warm-ups to incorporating dynamic stretching routines. However, the optimal
      volume of dynamic drills is yet to be identified. The aim of this repeated
      measures study was to examine varying volumes (1, 2, and 3 sets) of active
      dynamic stretching (ADS) in a warm-up on 10- and 20-m sprint performance. With a
      within-subject design, 16 highly trained male participants (age: 20.9 +/- 1.3
      years; height: 179.7 +/- 5.7 cm; body mass: 72.7 +/- 7.9 kg; % body fat: 10.9 +/-
      2.4) completed a 5-minute general running warm-up before performing 3
      preintervention measures of 10- to 20-m sprint. The interventions included 1, 2,
      and 3 sets of active dynamic stretches of the lower-body musculature
      (gastrocnemius, gluteals, hamstrings, quadriceps, and hip flexors) performed
      approximately 14 times for each exercise while walking (ADS1, ADS2, and ADS3).
      The active dynamic warm-ups were randomly allocated before performing a sprint
      specific warm-up. Five minutes separated the end of the warm-up and the 3
      postintervention measures of 10- to 20-m sprints. There were no significant time,
      condition, and interaction effects over the 10-m sprint time. For the 0- to 20-m
      sprint time, a significant main effect for the pre-post measurement (F = 10.81; p
      < 0.002), the dynamic stretching condition (F = 6.23; p = 0.004) and an
      interaction effect (F = 41.19; p = 0.0001) were observed. A significant decrease
      in sprint time (improvement in sprint performance) post-ADS1 (2.56%, p = 0.001)
      and post-ADS2 (2.61%, p = 0.001) was observed. Conversely, the results indicated
      a significant increase in sprint time (sprint performance impairment) post-ADS3
      condition (2.58%, p = 0.001). Data indicate that performing 1-2 sets of 20 m of
      active dynamic stretches in a warm-up can enhance 20-m sprint performance. The
      results delineated that 3 sets of ADS repetitions could induce acute fatigue and
      impair sprint performance within 5 minutes of the warm-up.

PMID- 22158261
TI  - Physiological strain associated with high-intensity hypoxic intervals in highly
      trained young runners.
AB  - To examine the physiological strain associated with hypoxic high intensity
      interval training (HHIT), 8 highly trained young runners (age, 18.6 +/- 5.3
      years) randomly performed, 5 * 3-minute intervals in either normoxic (N, 90% of
      the velocity associated with VO(2max), vVO(2max)) or hypoxic (H, simulated 2,400
      m altitude, 84% of nuVO(2max)) conditions. Cardiorespiratory (ventilation [V(E)],
      oxygen consumption [V(O2)], heart rate [HR], oxygen saturation [SpO(2)]), rating
      of central perceived exertion (RPE(C)) responses, changes in neutrophils,
      erythropoietin (EPO), blood lactate ([La]) and, bicarbonate ([HCO(-)(3)]), vagal
      related indices of HR variability (natural logarithm of the square root of the
      mean of the sum of the squares of differences [Ln rMSSD]) and maximal sprint and
      jump performances were compared after each session. Compared with N, H was
      associated with similar V(E) (Cohen's d +/- 90% confidence limits, 0.0 +/- 0.4,
      with % chances of higher/similar/lower values of 15/61/24) but at least lower
      VO(2) (-0.8 +/- 0.4, 0/0/100), HR (-0.4 +/- 0.4, 1/21/78), and SpO(2) (-1.8 +/-
      0.4, 0/0/100). Rating of perceived exertion was very likely higher (+0.5 +/- 0.4,
      92/8/0). Changes in [HCO(3)] (-0.6 +/- 0.8, 5/13/83), [La] (+0.2 +/- 0.4,
      52/42/5), and EPO (+0.2 +/- 0.4, 55/40/5) were at least possibly greater after H
      compared with those after N, whereas changes in neutrophils were likely lower (
      0.5 +/- 0.7, 4/15/81). Changes in 20-m sprint time (+0.20 +/- 0.23, 49/50/1) were
      possibly lower after H. There was no clear difference in the changes in Ln rMSSD
      (+0.2 +/- 1.7, 48/18/34) and jump (+0.3 +/- 0.9, 60/25/15). In conclusion,
      although perceived as harder, HHIT is not associated with an exaggerated
      physiological stress in highly trained young athletes. The present results also
      confirm that HHIT may not be optimal for training both the cardiorespiratory and
      neuromuscular determinants of running performance in this population.

PMID- 22158262
TI  - Improving lower limb weight distribution asymmetry during the squat using
      Nintendo Wii Balance Boards and real-time feedback.
AB  - Weight-bearing asymmetry (WBA) may be detrimental to performance and could
      increase the risk of injury; however, detecting and reducing it is difficult in a
      field setting. This study assessed whether a portable and simple-to-use system
      designed with multiple Nintendo Wii Balance Boards (NWBBs) and customized
      software can be used to evaluate and improve WBA. Fifteen elite Australian Rules
      Footballers and 32 age-matched, untrained participants were tested for measures
      of WBA while squatting. The NWBB and customized software provided real-time
      visual feedback of WBA during half of the trials. Outcome measures included the
      mean mass difference (MMD) between limbs, interlimb symmetry index (SI), and
      percentage of time spent favoring a single limb (TFSL). Significant reductions in
      MMD (p = 0.028) and SI (p = 0.007) with visual feedback were observed for the
      entire group data. Subgroup analysis revealed significant reductions in MMD (p =
      0.047) and SI (p = 0.026) with visual feedback in the untrained sample; however,
      the reductions in the trained sample were nonsignificant. The trained group
      showed significantly less WBA for TFSL under both visual conditions (no feedback:
      p = 0.015, feedback: p = 0.017). Correlation analysis revealed that participants
      with high levels of WBA had the greatest response to feedback (p < 0.001, rho =
      0.557). In conclusion, WBA exists in healthy untrained adults, and these
      asymmetries can be reduced using real-time visual feedback provided by an NWBB
      based system. Healthy, well-trained professional athletes do not possess the same
      magnitude of WBA. Inexpensive, portable, and widely available gaming technology
      may be used to evaluate and improve WBA in clinical and sporting settings.

PMID- 22158263
TI  - High birth weight and obesity--a vicious circle across generations.
AB  - OBJECTIVES: Rates of high birth weight infants, overweight and obese children and
      adults are increasing. The associations between birth weight and adult weight may
      have consequences for the obesity epidemic across generations. We examined the
      association between mothers' birth weight for gestational age and adult body mass
      index (BMI) and these factors' joint effect on risk of having a large-for
      gestational-age (LGA) offspring (>+2 s.d. above the mean). DESIGN: A cohort of
      162 676 mothers and their first-born offspring with birth information recorded on
      mothers and offspring in the nation-wide Swedish Medical Birth Register 1973
      2006. RESULTS: Compared with mothers with appropriate birth weight for
      gestational age (AGA; -1 to +1 s.d.), mothers born LGA had increased risks of
      overweight (BMI 25.0-29.9; odds ratio (OR), 1.50; 95% CI 1.39-1.61), obesity
      class I (BMI 30.0-34.9; OR 1.77; 95% CI 1.59-1.98), obesity class II (BMI 35.0
      39.9; OR 2.77; 95% CI 2.37-3.24) and obesity class III (BMI >=40.0; OR 2.04; 95%
      CI 1.49-2.80). In each stratum of mother's birth weight for gestational age, risk
      of having an LGA offspring increased with mother's BMI. The risk of an LGA
      offspring was highest among women with a high (>=30) BMI who also had a high
      birth weight for gestational age (>+1 s.d.). In these groups, the ORs for LGA
      offspring ranged from 5 to 14 when compared with mothers born AGA with normal BMI
      (<=24.9). However, the strongest increase in risk by BMI was seen among mothers
      born SGA: the OR of having an LGA offspring was 13 times as high among SGA
      mothers with BMI >=35.0 compared with the OR among SGA mothers with normal BMI
      (ORs=4.61 and 0.35, respectively). CONCLUSIONS: Prenatal conditions are important
      for the obesity epidemic. Prevention of LGA births may contribute to curtail the
      intergenerational vicious cycle of obesity.

PMID- 22158264
TI  - Genetic variants in vitamin D metabolism-related genes and body mass index:
      analysis of genome-wide scan data of approximately 7000 Chinese women.
AB  - Vitamin D deficiency has been consistently associated with obesity. However, it
      is unclear whether vitamin D deficiency is the cause or consequence of obesity.
      We investigated this question by evaluating the association between genetic
      variants in vitamin D metabolism pathway genes and obesity-related traits. Using
      directly genotyped and imputed data from a genome-wide association study of 6922
      women aged 25-70 years, we examined the association of 198 single-nucleotide
      polymorphisms (SNPs) in vitamin D pathway genes (CYP27A1, CYP27B1, CYP24A1,
      CYP2R1, group-specific component (GC) and vitamin D nuclear receptor (VDR)) with
      body mass index (BMI) and body weight. Per allele beta (beta) estimates were
      calculated for this association using linear regression models, controlling for
      age, square of age, menopausal status and sample sets. Overall, only two SNPs
      (rs2248359 in CYP24A1 and rs10832313 in CYP2R1) had a nominally significant
      association with BMI and weight (P<0.05 for all), with no variation observed by
      menopausal status, physical activity or dietary energy intake. None of the SNPs
      examined in the VDR gene were associated with BMI or weight. Our findings suggest
      that common genetic variants in vitamin D pathway genes do not have a major role
      in obesity among Chinese women. This comprehensive evaluation of genetic
      polymorphisms in vitamin D metabolism-related genes and obesity-related traits
      did not provide strong evidence to support low vitamin D levels as a cause of
      obesity.

PMID- 22158265
TI  - Association between TV viewing, computer use and overweight, determinants and
      competing activities of screen time in 4- to 13-year-old children.
AB  - OBJECTIVE: TV viewing and computer use is associated with childhood overweight,
      but it remains unclear as to how these behaviours could best be targeted. The aim
      of this study was to determine to what extent the association between TV viewing,
      computer use and overweight is explained by other determinants of overweight, to
      find determinants of TV viewing and computer use in the home environment and to
      investigate competing activities. METHOD: A cross-sectional study was carried out
      among 4072 children aged 4-13 years in the city of Zwolle, the Netherlands. Data
      collection consisted of measured height, weight and waist circumference, and a
      parental questionnaire on socio-demographic characteristics, child's nutrition,
      physical activity (PA) and sedentary behaviour. Associations were studied with
      logistic regression analyses, for older and younger children, boys and girls
      separately. RESULTS: The odds ratio (OR) of being overweight was 1.70 (95%
      confidence interval (CI): 1.07-2.72) for viewing TV >1.5 h among 4- to 8-year-old
      children adjusted for all potential confounders. Computer use was not
      significantly associated with overweight. Determinants of TV viewing were as
      follows: having >2 TVs in the household (OR: 2.38; 95% CI: 1.66-3.41), a TV in
      the child's bedroom and not having rules on TV viewing. TV viewing and computer
      use were both associated with shorter sleep duration and not with less PA.
      CONCLUSION: Association between TV viewing and overweight is not explained by
      socio-demographic variables, drinking sugared drinks and eating snacks. Factors
      in the home environment influence children's TV viewing. Parents have a central
      role as they determine the number of TVs, rules and also their children's
      bedtime. Therefore, interventions to reduce screen time should support parents in
      making home environmental changes, especially when the children are young.

PMID- 22158266
TI  - Co-occurring weight problems among children with attention deficit/hyperactivity
      disorder: the role of executive functioning.
AB  - OBJECTIVE: To explore the link between pediatric obesity and attention
      deficit/hyperactivity disorder (ADHD) by examining whether executive functioning
      (EF) and medication status are associated with body mass index (BMI) and weight
      status in children with ADHD. METHOD: Participants for this study included 80
      children (mean age=10 years, 9 months) with a DSM-IV diagnosis of ADHD, confirmed
      by a comprehensive clinical diagnostic assessment. Children's EF was measured
      using three neuropsychological tests, and severity of ADHD symptoms and
      medication status were obtained from parent report. Children's height and weight
      were also measured during the visit using a wall-mounted stadiometer and a
      balance beam scale. RESULTS: Children with ADHD who performed poorly on the
      neuropsychological battery had greater BMI z-scores, and were more likely to be
      classified as overweight/obese compared with children with ADHD who performed
      better on the neuropsychological battery. In addition, children with ADHD who
      were taking a stimulant medication had significantly lower BMI z-scores compared
      with children with ADHD who were not taking medication or who were taking a non
      stimulant medication. CONCLUSION: EF is more impaired among children with ADHD
      and co-occurring weight problems, highlighting the importance of self-regulation
      as a link between pediatric obesity and ADHD.

PMID- 22158267
TI  - A novel obesity model: synphilin-1-induced hyperphagia and obesity in mice.
AB  - AIMS: The pathogenesis of obesity remains incompletely understood and the
      exploration of the role of novel proteins in obesity may provide important
      insights into its causes and treatments. Here, we report a previously
      unidentified role for synphilin-1 in the control of food intake and body weight.
      Synphilin-1, a cytoplasmic protein, was initially identified as an interaction
      partner of alpha-synuclein, and has implications in Parkinson's disease
      pathogenesis related to protein aggregation. SUBJECTS AND METHODS: To study the
      in vivo role of synphilin-1, we characterized a human synphilin-1 transgenic
      mouse (SP1) by assessing synphilin-1 expression, plasma parameters, food intake
      and spontaneous activity to determine the major behavioral changes and their
      consequences in the development of the obesity phenotype. RESULTS: Expression of
      human synphilin-1 in brain neurons in SP1 mice resulted in increased food intake,
      body weight and body fat. SP1 mice also displayed hyperinsulinemia,
      hyperleptinemia and impaired glucose tolerance. Pair-feeding SP1 mice to amounts
      consumed by non-transgenic mice prevented the increased body weight, adiposity,
      hyperinsulinemia and hyperleptinemia demonstrating that these were all the
      consequences of increased food intake. Transgenic expression of synphilin-1 was
      enriched in hypothalamic nuclei involved in feeding control, and fasting-induced
      elevated endogenous synphilin-1 levels at these sites, suggesting that synphilin
      1 is an important player in the hypothalamic energy balance regulatory system.
      CONCLUSION: These studies identify a novel function of synphilin-1 in controlling
      food intake and body weight, and may provide a unique obesity model for future
      studies of obesity pathogenesis and therapeutics.

PMID- 22158268
TI  - Impact of BMI on the incidence of metabolic abnormalities in metabolically
      healthy men.
AB  - OBJECTIVES: Although the existence of metabolically healthy obese (MHO)
      individuals has been recognized, little is known regarding metabolic health
      status in these subjects over time. Thus, we evaluated longitudinal changes in
      metabolic parameters among MHO subjects compared with metabolically healthy,
      normal-weight (MHNW) subjects. METHODS: A cohort study was performed on 2599
      Korean men, 30-59 years of age, with no evidence of fatty liver disease on
      ultrasound and no traits of metabolic syndrome at baseline. BMI was categorized
      based on criteria for Asian population. Study participants were followed annually
      or biennially between 2002 and 2009. At each visit, the fatty liver on ultrasound
      was assessed and metabolic abnormalities were measured. Parametric Cox models and
      a pooled logistic regression models were used to evaluate the relationships of
      BMI with incident metabolic abnormalities. RESULTS: During 9647.1 person-years of
      follow-up, 1673 participants developed metabolic abnormalities. After adjusting
      for age, smoking, alcohol intake and exercise, higher baseline BMI categories
      predicted increased incidences of metabolic abnormalities in a dose-response
      manner. The hazard ratios (95% confidence intervals) for hypertriglyceridemia,
      prediabetes, pre-hypertension, low high-density lipoprotein-cholesterol, fatty
      liver, elevated high sensitivity-C reactive protein, elevated homeostasis model
      assessment of insulin resistance, any metabolic abnormality and metabolic
      syndrome among the MHO subjects compared with the MHNW subjects were 1.51 (1.23
      1.85), 1.43 (1.19-1.72), 1.79 (1.45-2.22), 1.80 (1.30-2.49), 2.69 (2.19-3.31),
      1.39 (1.16-1.67), 2.90 (2.31-3.62), 1.68 (1.45-1.93) and 1.84(1.02-3.30),
      respectively. CONCLUSION: In this study, MHO individuals showed higher incidences
      of metabolic abnormalities compared with MHNW individuals. This suggests that
      initially MHO individuals undergo adverse metabolic changes associated with
      obesity over time.

PMID- 22158269
TI  - Genetic influences in childhood obesity: recent progress and recommendations for
      experimental designs.
AB  - The increasing prevalence of pediatric obesity around the world has become an
      area of scientific interest because of public health concern. Although since
      early stages of the lifespan body weight might be heavily influenced by an
      individual's behavior, epidemiological research highlights the involvement of
      genetic influences contributing to variation in fat accumulation and thus body
      composition. Results from genome-wide association studies and candidate gene
      approaches have identified specific regions across the human genome influencing
      obesity-related phenotypes. Reviewing the scientific literature provides support
      to the belief that at the conceptual level scientists understand that genes and
      environments do not act independently, but rather synergistically, and that such
      interaction might be the responsible factor for differences within and among
      populations. However, there is still limited understanding of genetic and
      environmental factors influencing fat accumulation and deposition among different
      populations, which highlights the need for innovative experimental designs,
      improved body composition measures and appropriate statistical methodology.

PMID- 22158270
TI  - Modelled impacts of badger culling on cattle TB in a real area with geographic
      boundaries.
AB  - As a part of bovine tuberculosis eradication strategy, the Welsh Government has
      proposed a badger cull in a defined area in and around North Pembrokeshire, and
      has published information on herd densities and incidence levels within and close
      to the area. In the present study, three sets of previously published data
      relating the impact of badger culling inside and around previous culling areas to
      distances from culling area boundaries have been used to model possible impacts
      of the proposed cull, taking account of three possible scenarios in which
      geographic boundaries reduce, to varying extents, adverse effects caused by
      increased badger movements. For the scenarios considered, the results predict
      average changes in confirmed herd incidences (CHIs) in the range -15.7 (-29.1 to
      1.6 per cent) to -25.3 per cent (-52.2 to 46.1 per cent) over a period of 10
      years, comprising average changes in the culling area in the range -26.1 (-34.8
      to -14.8 per cent) to -32.6 per cent (-59.6 to 47.6 per cent), and average
      changes on adjoining land in the range 4.5 (-21.8 to 39.8 per cent) to 7.8 per
      cent (-16.1 to 38.5 per cent). The overall impacts equate to average reductions
      in the number of CHIs of between 122 (37 to 187) and 158 (-254 to 304).

PMID- 22158271
TI  - Seroprevalence of Mycobacterium avium subspecies paratuberculosis in elks in
      Korea.

PMID- 22158272
TI  - Two-dimensional and M-mode echocardiographic reference values in healthy adult
      Saanen goats.
AB  - Echocardiography has become a routine non-invasive cardiac diagnostic tool in
      most species. Accurate measurement of cardiac dimensions requires reference
      values, which are poorly documented in goats. The aim of the present study was to
      test the inter-day repeatability and to establish the reference values of two
      dimensional (2D-) and time-motion (M-) mode echocardiographic variables in
      healthy adult Saanen goats. Six goats were investigated three times by the same
      observer at one-day interval using a standardised 2D- and M-mode
      echocardiographic protocol. The intra-observer inter-day repeatability was tested
      using analysis of variance, calculation of the coefficient of variation and
      confidence intervals. A single echocardiographic examination was performed in six
      other goats, and values obtained in the 12 goats were used to establish the 2D-
      and M-mode echocardiographic reference values in healthy adult female Saanen
      goats. Statistical analysis revealed a good inter-day repeatability of the
      echocardiographic cardiac measurements. Echocardiographic reference values
      obtained in healthy adult Saanen goats seemed slightly higher than those reported
      in healthy Swedish domestic goats and were similar to those reported in healthy
      adult sheep.

PMID- 22158273
TI  - Differential response of cancer cells to HDAC inhibitors trichostatin A and
      depsipeptide.
AB  - BACKGROUND: Over the last decade, several drugs that inhibit class I and/or class
      II histone deacetylases (HDACs) have been identified, including trichostatin A,
      the cyclic depsipeptide FR901228 and the antibiotic apicidin. These compounds
      have had immediate application in cancer research because of their ability to
      reactivate aberrantly silenced tumour suppressor genes and/or block tumour cell
      growth. Although a number of HDAC inhibitors are being evaluated in preclinical
      cancer models and in clinical trials, little is known about the differences in
      their specific mechanism of action and about the unique determinants of cancer
      cell sensitivity to each of these inhibitors. METHODS: Using a combination of
      cell viability assays, HDAC enzyme activity measurements, western blots for
      histone modifications, microarray gene expression analysis and qRT-PCR, we have
      characterised differences in trichostatin A vs depsipeptide-induced phenotypes in
      lung cancer, breast cancer and skin cancer cells and in normal cells and have
      then expanded these studies to other HDAC inhibitors. RESULTS: Cell viability
      profiles across panels of lung cancer, breast cancer and melanoma cell lines
      showed distinct sensitivities to the pan-inhibitor TSA compared with the class 1
      selective inhibitor depsipeptide. In several instances, the cell lines most
      sensitive to one inhibitor were most resistant to the other inhibitor,
      demonstrating these drugs act on at least some non-overlapping cellular targets.
      These differences were not explained by the HDAC selectivity of these inhibitors
      alone since apicidin, which is a class 1 selective compound similar to
      depsipeptide, also showed a unique drug sensitivity profile of its own. TSA had
      greater specificity for cancer vs normal cells compared with other HDAC
      inhibitors. In addition, at concentrations that blocked cancer cell viability,
      TSA effectively inhibited purified recombinant HDACs 1, 2 and 5 and moderately
      inhibited HDAC8, while depsipeptide did not inhibit the activity of purified
      HDACs in vitro but did in cellular extracts, suggesting a potentially indirect
      action of this drug. Although both depsipeptide and TSA increased levels of
      histone acetylation in cancer cells, only depsipeptide decreased global levels of
      transcriptionally repressive histone methylation marks. Analysis of gene
      expression profiles of an isogenic cell line pair that showed discrepant
      sensitivity to depsipeptide, suggested that resistance to this inhibitor may be
      mediated by increased expression of multidrug resistance genes triggered by
      exposure to chemotherapy as was confirmed by verapamil studies. CONCLUSION:
      Although generally thought to have similar activities, the HDAC modulators
      trichostatin A and depsipeptide demonstrated distinct phenotypes in the
      inhibition of cancer cell viability and of HDAC activity, in their selectivity
      for cancer vs normal cells, and in their effects on histone modifications. These
      differences in mode of action may bear on the future therapeutic and research
      application of these inhibitors.

PMID- 22158274
TI  - Lumbar vertebral fractures in children: four cases and review of the literature.
AB  - BACKGROUND: Vertebral fractures and severe injuries to the spine cord in children
      are rare and account for a small proportion of all childhood injuries. Pediatric
      vertebral and spinal cord injuries have unique characteristics depending on their
      age. Young children sustain upper cervical spine injuries, which are more serious
      injuries and have a higher mortality rate. Older children have lower spine
      injuries and thoracoabdominal injuries. OBJECTIVES: This study aimed to present
      the epidemiology and potential complications from lumbar spine fractures. CASES:
      There were 4 cases of older children who sustained lumbar vertebral fractures.
      CONCLUSIONS: Fractures of the lumbar spine in children, although relatively rare,
      are important to understand. Patterns of injury with vertebral and spinal cord
      injuries in children vary from those of adults. The biologic differences of
      children make differences in fracture patterns and alter the management necessary
      for successful treatment. Errors in management can have adverse effects on these
      injuries.

PMID- 22158275
TI  - Early extracorporeal life support as rescue for Wegener granulomatosis with
      diffuse alveolar hemorrhage and acute respiratory distress syndrome: a case
      report and literature review.
AB  - OBJECTIVE: The study's objective was to report a case and review the literature
      on the use of extracorporeal life support in the face of severe pulmonary
      hemorrhage for acute respiratory distress syndrome. STUDY SELECTION: This study
      is a single case report of a pediatric patient who was successfully managed on
      venovenous extracorporeal life support for severe acute respiratory distress
      syndrome with acute pulmonary hemorrhage secondary to Wegener disease.
      CONCLUSIONS: Extracorporeal life support can be used successfully in selected
      patients with respiratory failure with pulmonary hemorrhage. The cautious use of
      anticoagulation should be balanced with the risk of bleeding, mindful of the need
      for other measures to mitigate severe bleeding if this should occur.

PMID- 22158276
TI  - Traumatic pediatric olecranon injury: a report of suture fixation and review of
      the literature.
AB  - Elbow injuries make up to 3% to 4% of all emergency department presentations and
      are often difficult to diagnose. These injuries are often missed on radiographs
      because of the large cartilaginous component of the pediatric elbow resulting in
      malunion. Fractures around the elbow joint are one of the leading causes of
      litigation claim, and awareness of the pitfalls in diagnosis of these subtle
      injuries is necessary for a prompt diagnosis. Fracture of the olecranon epiphysis
      is rare and often being described around puberty and in association with
      osteogenesis imperfecta. Management using K-wire tension band fixation has been
      described in the past, which can lead to growth arrest in younger patients.We
      hereby present a missed rare sleeve-type open olecranon epiphyseal fracture in a
      young child, highlighting the pitfalls in the diagnosis of these injuries. This
      article also reviews various options to manage such a rare fracture and also
      suggests an alternative method of transosseous suture fixation with an excellent
      result.

PMID- 22158277
TI  - A child with leukocoria.
AB  - Leukocoria, meaning "white pupil," describes the clinical finding of a white
      pupillary reflex on examination. It may be discovered through an asymmetric red
      reflex using direct ophthalmoscopy, or it may be seen incidentally on flash
      photography. It results from an abnormality of the eyeball that interferes with
      the normal reflective process. We report a case of a 3-year-old boy who presents
      with leukocoria found to be caused by a retinoblastoma and discuss the
      differential diagnosis of this uncommon presentation to the pediatric emergency
      department.

PMID- 22158278
TI  - Wide complex tachycardia in a pediatric diphenhydramine overdose treated with
      sodium bicarbonate.
AB  - INTRODUCTION: Diphenhydramine is an antihistamine commonly implicated in
      overdose. It has many pharmacologic effects, including sodium channel blockade.
      Overdoses in toddlers causing QRS prolongation are only rarely reported and never
      with effective use of sodium bicarbonate. We report a diphenhydramine overdose in
      a toddler with multiple markers of sodium channel blockade effectively treated
      with sodium bicarbonate. METHODS: A 13-month-old infant girl was brought in by
      the emergency medical service for a witnessed tonic-clonic seizure. Two hours
      previously, the child had been found with an open bottle of 25-mg diphenhydramine
      tablets, 24 of which were missing. Midazolam was administered with seizure
      resolution. Examination revealed 4-mm reactive pupils; nystagmus; warm, dry,
      flushed skin; and altered mental status. Initial electrocardiograms revealed
      sinus tachycardia at a rate of 180 beats per minute, a prolonged QRS of 130
      milliseconds (from a baseline of 65 milliseconds), and a positive terminal R wave
      in aVR, which later resolved after sodium bicarbonate treatment. The patient was
      discharged home the following day with no sequelae. RESULTS AND DISCUSSION:
      Diphenhydramine toxicity is a common poisoning in children. Toxicity typically
      presents with signs and symptoms of the anticholinergic toxidrome.
      Diphenhydramine also has sodium channel-blocking properties, and this can be
      shown in the form of prolonged QRS and a terminal R wave in aVR. QRS prolongation
      and aVR abnormalities from diphenhydramine ingestion in a toddler have been
      reported, but effective use of sodium bicarbonate has not. CONCLUSIONS:
      Electrocardiographic finding consistent with sodium channel blockade should be
      recognized as a complication of pediatric diphenhydramine overdose, and they seem
      responsive to hypertonic sodium bicarbonate.

PMID- 22158279
TI  - Traumatic hip dislocation in a 3-year-old girl.
AB  - Traumatic hip dislocation in the pediatric patient requires much less energy than
      in an adult, yet it remains a rare diagnosis. We report the case of a 3-year-old
      girl who dislocated her right hip when bindings failed to release as she skied
      downhill. The hip was promptly reduced in the nearest trauma center, and at 18
      months after injury, there is no evidence of avascular necrosis. The potential
      risk of avascular necrosis is significant, and the risk rises greatly when
      reduction is delayed beyond 6 hours. Reduction can be safely performed in the
      emergency department, although up to 25% of cases will require open reduction in
      the operating room. A high index of suspicion is warranted to not miss the
      "golden window" and achieve satisfactory reduction in a timely fashion.

PMID- 22158280
TI  - Gluconeogenesis defect presenting with resistant hyperglycemia and acidosis
      mimicking diabetic ketoacidosis.
AB  - Fructose-1,6-diphosphatase (FDPase) enzyme deficiency is a rare inherited
      metabolic disease. Affected patients usually present with metabolic crisis
      including hypoglycemia, acidosis, ketonuria, and hyperuricemia. A previously
      healthy 8-month-old male infant presented with fever, vomiting, and hypoactivity.
      He had tachycardia, tachypnea, and a tendency to sleep. The patient had signs of
      severe dehydration and shock. Laboratory findings revealed significant lactic
      acidosis, hyperuricemia, hyperglycemia, elevated liver enzyme level, and
      hyperlipidemia. The urine analysis had evidence of glycosuria and ketonuria.
      Hyperuricemia, lactic acidemia, and hyperglycemia persisted despite insulin
      infusion, adequate hydration, and perfusion. Consequently, peritoneal dialysis
      was started. About 12 hours after dialysis, his metabolic derangements were
      normalized, and clinical status was improved dramatically. His metabolic disease
      workup was compatible with FDPase deficiency. Here, we described a metabolic
      attack of FDPase deficiency presented with hyperglycemia mimicking diabetic
      ketoacidosis.

PMID- 22158281
TI  - Cornual ectopic pregnancy in a female with initial negative ultrasound.
AB  - Cornual pregnancies are a rare form of ectopic pregnancy that can be misdiagnosed
      as an intrauterine pregnancy via ultrasound. We report a 16-year-old adolescent
      girl with a cornual ectopic pregnancy and subsequent rupture in the emergency
      department.

PMID- 22158282
TI  - Purulent pericarditis in children: is pericardiotomy needed?
AB  - OBJECTIVES: This study aimed to describe our experience with pediatric bacterial
      pericarditis and review the optimal therapy for this entity. METHODS: This is a
      retrospective study in a pediatric intensive care unit in a university hospital.
      Three children were diagnosed with purulent pericarditis. They were all treated
      with antibiotics, echocardiography-guided pericardial fluid drainage, and
      placement of a pericardial catheter, with no need for thoracotomy or pericardial
      window. RESULTS: All 3 children fully recovered, and none developed constrictive
      pericarditis. CONCLUSIONS: Children with purulent pericarditis usually can be
      treated with antibiotics and drainage of pericardial effusion, with no need for
      thoracotomy or pericardial window.

PMID- 22158283
TI  - Three faces of costal exostoses: case series and review of literature.
AB  - The 3 cases presented here involve 3 unusual and different complications of
      costal exostoses: spontaneous hemothorax, pneumothorax, and pericardial effusion.
      All of the cases presented with chest pain to the emergency department. Two of
      the cases have hereditary multiple exostoses. All but one of the patients
      required surgical intervention. Complications of costal exostoses are rare, but
      hemothorax, pneumothorax, and pericardial effusions can occur.

PMID- 22158284
TI  - Spinal cord injuries in older children: is there a role for high-dose
      methylprednisolone?
AB  - We present a retrospective case series of 15 children (aged 8-16 years) with
      blunt traumatic spinal cord injury who were treated with methylprednisolone as
      per the National Acute Spinal Cord Injury Study protocol. Of all patients, 12
      (80%) were male. Causes were sports injuries (n = 9), motor vehicle crashes (n =
      2), and falls (n = 4). Most injuries were nonskeletal (n = 14), and all patients
      had incomplete injury of the spinal cord. The most common location of tenderness
      was cervical (n = 7). Of the 15 patients, methylprednisolone was initiated within
      3 hours in 13 patients and between 3 and 8 hours in 2 patients. All patients
      received the medication for 23 hours as per the National Acute Spinal Cord Injury
      Study protocol. Of the 15 patients, 13 recovered completely by 24 hours and were
      discharged with a diagnosis of spinal cord concussion. One patient had
      compression fracture of T5 and T3-T5 spinal contusion but no long-term
      neurological deficit. One patient was discharged with diagnosis of C1-C3 spinal
      cord contusion (by magnetic resonance imaging) and had partial recovery at 2
      years after injury. All patients with a diagnosis of cord concussion had normal
      plain films of the spine and computed tomographic and magnetic resonance imaging
      findings. None of the patients had any associated major traumatic injuries to
      other organ systems. The high-dose steroid therapy did not result in any serious
      bacterial infections.

PMID- 22158285
TI  - Necrotizing fasciitis.
AB  - Necrotizing fasciitis (NF) is a rare, rapidly progressive bacterial soft tissue
      infection with a high risk for morbidity and mortality. Although more common in
      adults, NF also affects the pediatric population. Many bacterial organisms can
      cause NF, but group A Streptococcus is the most common monomicrobial cause of
      disease. Necrotizing fasciitis remains principally a clinical diagnosis, and it
      is often missed early in its presentation because of the difficulty in
      differentiating it from more common soft tissue infections. The criterion
      standard for diagnosis and the mainstay of therapy are surgical debridement. Time
      to initiation and completion of therapy remains the most important factor in
      patient outcome, highlighting the importance of early recognition and
      intervention in this potentially devastating disease.

PMID- 22158287
TI  - ECGs in the ED.

PMID- 22158288
TI  - The not-so-nice spice: a teenage girl with palpitations and dry mouth.

PMID- 22158289
TI  - An international fellowship training program in pediatric emergency medicine:
      establishing a new subspecialty in the Land of the Dragon.
AB  - INTRODUCTION: The health care system reform in the People's Republic of China has
      brought plans for establishment of a universal coverage for basic health
      services, including services for children. This effort demands significant change
      in health care planning. Pediatric emergency medicine (PEM) is not currently
      identified as a specialty in China, and emergency medicine systems suffer from
      lack of appropriate training.In 2006, the Centre for International Child Health
      and the Department of Pediatrics, British Columbia Children's Hospital,
      Vancouver, Canada, initiated a fellowship training program in PEM for
      pediatricians working in emergency departments or critical care settings with the
      Children's Hospital of Fudan University, China. The main objective was to upgrade
      the professional and clinical experience of emergency physicians practicing PEM
      and build PEM capacity throughout China by training the future trainers. METHODS:
      After selecting trainees, the program included a structured curriculum over 2
      years of training in China by Canadian and Australian PEM faculty and then
      practical exposure to PEM in Canada. All trainees underwent a structured
      evaluation after their final rotation in Canada. RESULTS: A total of 12 trainees
      completed the first 2 program cycles. The trainees considered the "overall rating
      of the training experience" as "excellent" (10/12) or "good" (2/12). All trainees
      considered the program as a relevant training to their practice and felt it will
      change their practice. They reported the program to be effective, with excellent
      complexity of content. DISCUSSION: Despite its current success, the program faces
      challenges in the development of the new subspecialty and ensuring its acceptance
      among other health care providers and decision makers. Identification and
      preparation of a capable training force to lead educational activities in China
      are daunting tasks. Time constraints, funding, and language barriers are other
      challenges. Future effort should be focused on improving and sustaining
      resuscitation capacity and enhancing triage systems.

PMID- 22158290
TI  - Pediatric emergency medicine: legal briefs.

PMID- 22158291
TI  - Measuring pain in children with cognitive impairment and cerebral palsy: a
      multiregional survey in the use of specific pain scales.

PMID- 22158293
TI  - Influenza.

PMID- 22158294
TI  - Public health: Life lessons.

PMID- 22158295
TI  - Morbidity: A personal response.

PMID- 22158296
TI  - Epidemiology: Racing against the flu.

PMID- 22158297
TI  - Q&A: The flu catcher. An interview with Richard Webby by Rebecca Kessler.

PMID- 22158298
TI  - Prevention: Vaccine for all seasons.

PMID- 22158299
TI  - Drugs: Lines of defence.

PMID- 22158300
TI  - Comparative analysis of isocentric 3-dimensional C-arm fluoroscopy and biplanar
      fluoroscopy for anterior screw fixation in odontoid fractures.
AB  - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To compare long-term
      radiographic and clinical outcomes of patients undergoing anterior odontoid screw
      placement using traditional biplanar fluoroscopy or isocentric 3-dimensional C
      arm (iso-C) fluoroscopy-assisted techniques. SUMMARY OF BACKGROUND DATA: Anterior
      screw fixation of odontoid fractures preserves motion at the C1-C2 joint, but
      accurate screw positioning is essential for successful outcomes. Biplanar
      fluoroscopy image guidance is most often used; however, iso-C imaging improves
      the ease and accuracy of screw placement with less radiation exposure. METHODS:
      Fifty-one patients underwent anterior odontoid screw fixation for type II (48
      patients) and rostral type III fractures (3 patients). Procedures were guided by
      biplanar fluoroscopy in 25 (49%) patients, and with iso-C assistance in 26 (51%).
      Length of surgery, complications, and clinical outcomes based on the Smiley
      Webster score were evaluated. Computed tomography confirmed adequate screw
      placement. Follow-up ranged from 3 to 9 months. RESULTS: At 3-month follow-up,
      screw position and fusion across the fracture were evident in 87% of the cases
      treated with biplanar fluoroscopy and in 100% treated by iso-C. The average
      outcome score in the iso-C group was superior to that of the biplanar group (1.08
      vs. 1.33, respectively), although not statistically significant. At last follow
      up, the rate of successful fusion was 88% in the biplanar group and 95% in the
      iso-C group. Length of surgery was significantly lower in the iso-C group
      compared with the biplanar group (P=0.05). The significantly longer preparation
      time in the iso-C group (P=0.04) accounted for no overall difference in total
      operating room occupancy time between the 2 groups. CONCLUSIONS: Iso-C
      significantly decreased surgical time. At last follow-up iso-C assistance was
      associated with improved rates of radiographic fusion with comparable outcome and
      complication profiles. This series represents the largest cohort of patients
      treated with intraoperative real-time navigation assistance for odontoid
      fractures.

PMID- 22158301
TI  - Influencing segmental balance in isthmic spondylolisthesis using transforaminal
      lumbar interbody fusion.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The objective of the study
      was to analyze segmental balance in patients with isthmic spondylolisthesis
      undergoing single-level transforaminal lumbar interbody fusion (TLIF). SUMMARY OF
      BACKGROUND DATA: Sagittal malalignment of the fused segment was suggested to be
      associated with degeneration of the adjacent segment. Meticulous surgical
      technique and particular attention to hardware positioning with the aim to
      restore segmental balance at the fusion level have been recommended to achieve
      better long-term clinical outcomes, but no single study addressed all proposed
      factors. METHODS: Standard lateral radiographs of the lumbosacral spine in the
      neutral standing position were retrospectively obtained for 32 patients
      undergoing single-level TLIF. Preoperative versus postoperative versus final
      follow-up (12 to 60 mo) values of translational slip (TS), posterior disc space
      height (PDSH), and segmental lordosis (SL) were compared using paired samples t
      test. Change in SL postoperatively between groups of next grouping variables:
      type and position of the interbody device, and rod contouring, was compared using
      2-tailed independent samples t test. Association between position of the
      interbody device and immediate PDSH was addressed with regression analysis
      postoperatively and at final follow-up. RESULTS: Mean TS decreased (P<0.001) and
      mean PDSH increased (P=0.002), but no significant change in SL occurred
      postoperatively (P=0.811). Increase in SL was observed with ventral positioning
      of the interbody device (P=0.009) and with bending of connecting rods (P=0.023).
      During follow-up, there was increase in TS (P=0.002) and decrease in PDSH
      (P<0.001) and SL (P<0.001) compared with postoperative values. Lower PDSH was
      found to be associated with more ventral positioning of the interbody device,
      both postoperatively (P=0.035) and at final follow-up (P=0.029). CONCLUSIONS:
      This study demonstrates that reduction of TS and restoration of disc space height
      are readily achieved with single-level TLIF. However, to establish an increase in
      SL consistent rod contouring and meticulous anterior placement of the interbody
      device should be applied. Excessive ventral positioning of the cages might result
      in insufficient disc space height restoration.

PMID- 22158302
TI  - What is the optimum fusion technique for adult isthmic spondylolisthesis--PLIF or
      PLF? A long-term prospective cohort comparison study.
AB  - STUDY DESIGN: Long-term prospective observational cohort study. OBJECTIVE: The
      objective of the study was to compare the long-term functional outcomes of
      posterolateral fusion (PLF) and posterior lumbar interbody fusion (PLIF) for the
      treatment of adult isthmic spondylolisthesis (IS). SUMMARY OF BACKGROUND DATA:
      PLIF has the theoretical advantage of improving sagittal alignment and providing
      a larger, more consistent fusion mass in patients with IS compared with PLF.
      Studies to date though have not shown a clinical difference, with follow-up of 2
      years. METHODS: An prospective cohort study was performed of a single surgeon's
      patients with IS treated surgically over a 10-year period. Average follow-up was
      7 years and 10 months. Preoperative patient characteristics between the 2 groups
      were not significantly different. The return rate of the long-term questionnaires
      was 83%. Outcome measures were the Roland Morris Disability Questionnaire (RMDQ),
      Low Back Outcome Score (LBOS), Short Form (SF)-12v2, and SF-6D R2. RESULTS: PLIF
      provided better short-term and long-term results than PLF. The PLIF group had
      significantly better LBOS scores in the long term, and nonsignificantly better
      RMDQ scores. As measured by the RMDQ Minimal Clinically Important Difference set
      at 4 and 8, the LBOS Minimal Clinically Important Difference set at 7.5 points
      and by SF-12v2 Physical Component Score, PLIF patients performed better than PLF
      patients. When analyzing single-level fusions alone, the difference is more
      pronounced, with Physical Component Score, Mental Component Scores, and SF-6D R2
      all being significantly better in the PLIF group rather than the PLF group.
      CONCLUSIONS: This study strongly supports the use of PLIF to obtain equivalent or
      superior clinical outcomes compared with PLF for spinal fusion for lumbar IS.
      Although there are considerable issues when commenting on the results of
      observational studies, the results of this study are the first to report long
      term follow-up beyond 2 years, and further larger long-term randomized studies
      are suggested.

PMID- 22158303
TI  - Intracranial implantation with subsequent 3D in vivo bioluminescent imaging of
      murine gliomas.
AB  - The mouse glioma 261 (GL261) is recognized as an in vivo model system that
      recapitulates many of the features of human glioblastoma multiforme (GBM). The
      cell line was originally induced by intracranial injection of 3-methyl
      cholantrene into a C57BL/6 syngeneic mouse strain (1); therefore, immunologically
      competent C57BL/6 mice can be used. While we use GL261, the following protocol
      can be used for the implantation and monitoring of any intracranial mouse tumor
      model. GL261 cells were engineered to stably express firefly luciferase (GL261
      luc). We also created the brighter GL261-luc2 cell line by stable transfection of
      the luc2 gene expressed from the CMV promoter. C57BL/6-cBrd/cBrd/Cr mice (albino
      variant of C57BL/6) from the National Cancer Institute, Frederick, MD were used
      to eliminate the light attenuation caused by black skin and fur. With the use of
      albino C57BL/6 mice; in vivo imaging using the IVIS Spectrum in vivo imaging
      system is possible from the day of implantation (Caliper Life Sciences,
      Hopkinton, MA). The GL261-luc and GL261-luc2 cell lines showed the same in vivo
      behavior as the parental GL261 cells. Some of the shared histological features
      present in human GBMs and this mouse model include: tumor necrosis,
      pseudopalisades, neovascularization, invasion, hypercellularity, and inflammation
      (1). Prior to implantation animals were anesthetized by an intraperitoneal
      injection of ketamine (50 mg/kg), xylazine (5 mg/kg) and buprenorphine (0.05
      mg/kg), placed in a stereotactic apparatus and an incision was made with a
      scalpel over the cranial midline. A burrhole was made 0.1 mm posterior to the
      bregma and 2.3mm to the right of the midline. A needle was inserted to a depth of
      3mm and withdrawn 0.4 mm to a depth of 2.6 mm. Two MUl of GL261-luc or GL261-luc2
      cells (10(7) cells/ml) were infused over the course of 3 minutes. The burrhole
      was closed with bonewax and the incision was sutured. Following stereotactic
      implantation the bioluminescent cells are detectable from the day of implantation
      and the tumor can be analyzed using the 3D image reconstruction feature of the
      IVIS Spectrum instrument. Animals receive a subcutaneous injection of 150 MUg
      luciferin /kg body weight 20 min prior to imaging. Tumor burden is quantified
      using mean tumor bioluminescence over time. Tumor-bearing mice were observed
      daily to assess morbidity and were euthanized when one or more of the following
      symptoms are present: lethargy, failure to ambulate, hunched posture, failure to
      groom, anorexia resulting in >10% loss of weight. Tumors were evident in all of
      the animals on necropsy.

PMID- 22158304
TI  - Contrasting connectivity of the ventralis intermedius and ventralis oralis
      posterior nuclei of the motor thalamus demonstrated by probabilistic
      tractography.
AB  - BACKGROUND: Targeting of the motor thalamus for the treatment of tremor has
      traditionally been achieved by a combination of anatomical atlases and
      neuroimaging, intraoperative clinical assessment, and physiological recordings.
      OBJECTIVE: To evaluate whether thalamic nuclei targeted in tremor surgery could
      be identified by virtue of their differing connections with noninvasive
      neuroimaging, thereby providing an extra factor to aid successful targeting.
      METHODS: Diffusion tensor tractography was performed in 17 healthy control
      subjects using diffusion data acquired at 1.5-T magnetic resonance imaging (60
      directions, b value = 1000 s/mm, 2 * 2 * 2-mm3 voxels). The ventralis intermedius
      (Vim) and ventralis oralis posterior (Vop) nuclei were identified by a
      stereotactic neurosurgeon, and these sites were used as seeds for probabilistic
      tractography. The expected cortical connections of these nuclei, namely the
      primary motor cortex (M1) and contralateral cerebellum for the Vim and M1, the
      supplementary motor area, and dorsolateral prefrontal cortex for the Vop, were
      determined a priori from the literature. RESULTS: Tractogram signal intensity was
      highest in the dorsolateral prefrontal cortex and supplementary motor area after
      Vop seeding (P < .001, Wilcoxon signed-rank tests). High intensity was seen in M1
      after seeding of both nuclei but was greater with Vim seeding (P < .001).
      Contralateral cerebellar signal was highest with Vim seeding (P < .001).
      CONCLUSION: Probabilistic tractography can depict differences in connectivity
      between intimate nuclei within the motor thalamus. These connections are
      consistent with published anatomical studies; therefore, tractography may provide
      an important adjunct in future targeting in tremor surgery.

PMID- 22158309
TI  - Europe and direct-to-consumer genetic tests.

PMID- 22158311
TI  - The fraction of cancer attributable to lifestyle and environmental factors in the
      UK in 2010.

PMID- 22158310
TI  - Resequencing 50 accessions of cultivated and wild rice yields markers for
      identifying agronomically important genes.
AB  - Rice is a staple crop that has undergone substantial phenotypic and physiological
      changes during domestication. Here we resequenced the genomes of 40 cultivated
      accessions selected from the major groups of rice and 10 accessions of their wild
      progenitors (Oryza rufipogon and Oryza nivara) to >15 * raw data coverage. We
      investigated genome-wide variation patterns in rice and obtained 6.5 million high
      quality single nucleotide polymorphisms (SNPs) after excluding sites with missing
      data in any accession. Using these population SNP data, we identified thousands
      of genes with significantly lower diversity in cultivated but not wild rice,
      which represent candidate regions selected during domestication. Some of these
      variants are associated with important biological features, whereas others have
      yet to be functionally characterized. The molecular markers we have identified
      should be valuable for breeding and for identifying agronomically important genes
      in rice.

PMID- 22158312
TI  - 3. Cancers attributable to consumption of alcohol in the UK in 2010.

PMID- 22158313
TI  - 4. Cancers attributable to dietary factors in the UK in 2010. I. Low consumption
      of fruit and vegetables.

PMID- 22158314
TI  - 1. The fraction of cancer attributable to lifestyle and environmental factors in
      the UK in 2010.
AB  - The overall objective of the study is to estimate the percentage of cancers
      (excluding non-melanoma skin cancer) in the UK in 2010 that were the result of
      exposure to 14 major lifestyle, dietary and environmental risk factors: tobacco,
      alcohol, four elements of diet (consumption of meat, fruit and vegetables, fibre
      and salt), overweight, lack of physical exercise, occupation, infections,
      radiation (ionising and solar), use of hormones and reproductive history (breast
      feeding). The number of new cases attributable to suboptimal exposure levels in
      the past, relative to a theoretical optimum exposure distribution, is evaluated.
      For most of the exposures, the attributable fraction was calculated based on the
      distribution of exposure prevalence (around 2000), the difference from the
      theoretical optimum (by age group and sex) and the relative risk per unit
      difference. For tobacco smoking, the method developed by Peto et al (1992) was
      used, which relies on the ratio between observed incidence of lung cancer in
      smokers and that in non-smokers, to calibrate the risk. This article outlines the
      structure of the supplement - a section for each of the 14 exposures, followed by
      a Summary chapter, which considers the relative contributions of each factor to
      the total number of cancers diagnosed in the UK in 2010 that were, in theory,
      avoidable.

PMID- 22158315
TI  - 5. Cancers attributable to dietary factors in the UK in 2010. II. Meat
      consumption.

PMID- 22158316
TI  - 6. Cancers attributable to dietary factors in the UK in 2010. III. Low
      consumption of fibre.

PMID- 22158317
TI  - 7. Cancers attributable to dietary factors in the UK in 2010. IV. Salt.

PMID- 22158318
TI  - 8. Cancers attributable to overweight and obesity in the UK in 2010.

PMID- 22158319
TI  - 9. Cancers attributable to inadequate physical exercise in the UK in 2010.

PMID- 22158320
TI  - 10. Cancers attributable to exposure to hormones in the UK in 2010.

PMID- 22158321
TI  - 11. Cancers attributable to infection in the UK in 2010.

PMID- 22158322
TI  - 12. Cancers in 2010 attributable to ionising radiation exposure in the UK.

PMID- 22158323
TI  - 2. Tobacco-attributable cancer burden in the UK in 2010.

PMID- 22158324
TI  - 13. Cancers attributable to solar (ultraviolet) radiation exposure in the UK in
      2010.

PMID- 22158325
TI  - 14. Cancers attributable to occupational exposures in the UK in 2010.

PMID- 22158326
TI  - 15. Cancers attributable to reproductive factors in the UK in 2010.

PMID- 22158327
TI  - 16. The fraction of cancer attributable to lifestyle and environmental factors in
      the UK in 2010.
AB  - This chapter summarises the results of the preceding sections, which estimate the
      fraction of cancers occurring in the UK in 2010 that can be attributed to sub
      optimal, past exposures of 14 lifestyle and environmental risk factors. For each
      of 18 cancer types, we present the percentage of cases attributable to one or all
      of the risk factors considered (tobacco, alcohol, four elements of diet
      (consumption of meat, fruit and vegetables, fibre, and salt), overweight, lack of
      physical exercise, occupation, infections, radiation (ionising and solar), use of
      hormones, and reproductive history (breast feeding)).Exposure to less than
      optimum levels of the 14 factors was responsible for 42.7% of cancers in the UK
      in 2010 (45.3% in men, 40.1% in women)--a total of about 134,000 cases.Tobacco
      smoking is by far the most important risk factor for cancer in the UK,
      responsible for 60, 000 cases (19.4% of all new cancer cases) in 2010. The
      relative importance of other exposures differs by sex. In men, deficient intake
      of fruits and vegetables (6.1%), occupational exposures (4.9%) and alcohol
      consumption (4.6%) are next in importance, while in women, it is overweight and
      obesity (because of the effect on breast cancer)--responsible for 6.9% of
      cancers, followed by infectious agents (3.7%).Population-attributable fractions
      provide a valuable quantitative appraisal of the impact of different factors in
      cancer causation, and are thus helpful in prioritising cancer control strategies.
      However, quantifying the likely impact of preventive interventions requires
      rather complex scenario modelling, including specification of realistically
      achievable population distributions of risk factors, and the timescale of change,
      as well as the latent periods between exposure and outcome, and the rate of
      change following modification in exposure level.

PMID- 22158330
TI  - A pharmacogenetic study of ADRB2 polymorphisms and indacaterol response in COPD
      patients.
AB  - Genetic variation in the ADRB2 gene has been hypothesized to have a role in
      differential response to beta-agonist (BA) therapy in asthma. However, study
      results have been inconsistent and the issue remains controversial. Furthermore,
      the impact of ADRB2 genetic variation on BA response in chronic obstructive
      pulmonary disease (COPD) patients has not been thoroughly studied. We carried out
      a large pharmacogenetic analysis testing for an association between common ADRB2
      polymorphisms and indacaterol response in COPD patients. A total of 648
      indacaterol-treated patients enrolled in two large randomized phase III studies
      were genotyped for the most commonly studied polymorphisms in the ADRB2 gene:
      Gly16Arg, Gln27Glu, Thr164Ile, and a variant in the 5' untranslated region
      (rs1042711). Our analysis showed little evidence for the association between
      these ADRB2 variants and indacaterol response, suggesting that ADRB2 genetic
      variation is unlikely to have a major role in differential response to
      indacaterol treatment in COPD patients.

PMID- 22158331
TI  - DNA-damage response gene polymorphisms and therapeutic outcomes in ovarian
      cancer.
AB  - Epithelial ovarian cancer has a poor prognosis owing to late diagnosis and
      frequent relapse after first-line therapy. Analysis of individual genetic
      variability could aid in the identification of markers, which could help in
      stratifying patients with the aim of optimizing individual therapy. In this study
      we assessed polymorphisms in three genes important in drugs' response in 97 early
      and 235 late-stage ovarian cancer patients. The Asp1104His polymorphism in xpg, a
      gene important for removal of platinum adducts, was associated with progression
      free survival in early- and late-stage ovarian cancer. Our data indicate that a
      simple diagnostic analysis such as xpg genotyping can help in predicting
      response, and extension to other possibly relevant genotypes could be useful in
      selecting patients with epithelial ovarian cancer for optimal therapy and hence
      increase the chance of response.

PMID- 22158332
TI  - How informative is a negative finding in a small pharmacogenetic study?
AB  - Many pharmacogenetic studies fail to yield any statistically significant
      associations. Such negative findings may be due to the absence of, or inadequate
      statistical power to test for, an effect at the genetic variants tested. In many
      instances, sample sizes are small, making it unclear how to interpret the absence
      of statistically significant findings. We demonstrate that the amount of
      information that can be drawn from a negative study is improved by incorporating
      statistical power and the added context of well-validated pharmacogenetic effects
      into the interpretation process. This approach permits clearer inferences to be
      made about the possible range of genetic effects that may be present in, or are
      likely absent from, small drug studies.

PMID- 22158329
TI  - Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect
      variation in transcriptional response.
AB  - Glucocorticoids (GCs) are steroid hormones widely used as pharmaceutical
      interventions, which act mainly by regulating gene expression levels. A large
      fraction of patients (~30%), especially those of African descent, show a weak
      response to treatment. To interrogate the contribution of variable
      transcriptional response to inter-ethnic differences, we measured in vitro
      lymphocyte GC sensitivity (LGS) and transcriptome-wide response to GCs in
      peripheral blood mononuclear cells from African-American (AA) and European
      American (EA) healthy donors. We found that transcriptional response after 8 h
      treatment was significantly correlated with variation in LGS within and between
      populations. We found that NFKB1, a gene previously found to predict LGS within
      populations, was more strongly downregulated in EAs on average. NFKB1 could not
      completely explain population differences, however, and we found an additional
      177 genes with population differences in the average log2 fold change (false
      discovery rate<0.05), most of which also showed a weaker transcriptional response
      in AAs. These results suggest that inter-ethnic differences in GC sensitivity
      reflect variation in transcriptional response at many genes, including regulators
      with large effects (for example, NFKB1) and numerous other genes with smaller
      effects.

PMID- 22158333
TI  - Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity.
AB  - The aim of this study was to investigate pharmacogenetic determinants of skin
      rash associated with epidermal growth factor receptor (EGFR) inhibitor treatment.
      A total of 109 prospectively sampled cancer patients, receiving the first
      treatment with an EGFR inhibitor, were genotyped for functional EGFR
      polymorphisms and tagging variants in genes involved in receptor downstream
      signaling. Skin rash was absent in 26 (23.9%) patients and associated with
      shorter overall survival compared with patients presenting skin rash (P=0.005).
      The EGFR polymorphisms, 497G/A (P=0.008), and the haplotypes of the promoter
      variants, EGFR-216G/T and -191C/A (P=0.029), were associated with the appearance
      of skin rash. In addition, a common haplotype in the PIK3CA gene was associated
      with skin rash (P=0.045) and overall survival (P=0.009). In conclusion, genetic
      variation within the EGFR gene and its downstream signaling partner PIK3CA might
      predict EGFR-inhibitor-related skin rash.

PMID- 22158334
TI  - Comment on "A role for immature myeloid cells in immune senescence".

PMID- 22158335
TI  - Comment on "Cyclophilin A is a damage-associated molecular pattern molecule that
      mediates acetaminophen-induced liver injury".

PMID- 22158336
TI  - Retraction. Targeting neural-restrictive silencer factor sensitizes tumor cells
      to antibody-based cancer immunotherapy in vitro via multiple mechanisms.

PMID- 22158337
TI  - Determination of molecular structures of HIV envelope glycoproteins using cryo
      electron tomography and automated sub-tomogram averaging.
AB  - Since its discovery nearly 30 years ago, more than 60 million people have been
      infected with the human immunodeficiency virus (HIV) (www.usaid.gov). The virus
      infects and destroys CD4+ T-cells thereby crippling the immune system, and
      causing an acquired immunodeficiency syndrome (AIDS) (2). Infection begins when
      the HIV Envelope glycoprotein "spike" makes contact with the CD4 receptor on the
      surface of the CD4+ T-cell. This interaction induces a conformational change in
      the spike, which promotes interaction with a second cell surface co-receptor
      (5,9). The significance of these protein interactions in the HIV infection
      pathway makes them of profound importance in fundamental HIV research, and in the
      pursuit of an HIV vaccine. The need to better understand the molecular-scale
      interactions of HIV cell contact and neutralization motivated the development of
      a technique to determine the structures of the HIV spike interacting with cell
      surface receptor proteins and molecules that block infection. Using cryo-electron
      tomography and 3D image processing, we recently demonstrated the ability to
      determine such structures on the surface of native virus, at ~20 A resolution
      (9,14). This approach is not limited to resolving HIV Envelope structures, and
      can be extended to other viral membrane proteins and proteins reconstituted on a
      liposome. In this protocol, we describe how to obtain structures of HIV envelope
      glycoproteins starting from purified HIV virions and proceeding stepwise through
      preparing vitrified samples, collecting, cryo-electron microscopy data,
      reconstituting and processing 3D data volumes, averaging and classifying 3D
      protein subvolumes, and interpreting results to produce a protein model. The
      computational aspects of our approach were adapted into modules that can be
      accessed and executed remotely using the Biowulf GNU/Linux parallel processing
      cluster at the NIH (http://biowulf.nih.gov). This remote access, combined with
      low-cost computer hardware and high-speed network access, has made possible the
      involvement of researchers and students working from school or home.

PMID- 22158338
TI  - Coronary Events in HIV-Infected Patients.

PMID- 22158339
TI  - Introduction to Special Section on HIV/AIDS and Substance Use in the Caribbean
      (Part 3): Perspectives on Substance Abuse Treatment as HIV Prevention and
      Implementation Science in the Youth Culture of Web 2.0.

PMID- 22158340
TI  - Tilting toward secrecy.

PMID- 22158341
TI  - European court bans embryonic stem cell patents.

PMID- 22158344
TI  - GlaxoSmithKline malaria vaccine phase 3 trial heralded.

PMID- 22158345
TI  - Interest groups jostle to influence PDUFA V.

PMID- 22158347
TI  - Industry continues dabbling with open innovation models.

PMID- 22158350
TI  - New startup models emerge as investor landscape shifts.

PMID- 22158352
TI  - Newsmaker: Zafgen.

PMID- 22158353
TI  - Shape shifting.

PMID- 22158354
TI  - Generation of the potent anti-malarial drug artemisinin in tobacco.

PMID- 22158355
TI  - Relative potential of biosynthetic pathways for biofuels and bio-based products.

PMID- 22158356
TI  - Re-evaluating PARP1 inhibitor in cancer.

PMID- 22158357
TI  - Access to human embryonic stem cell lines.

PMID- 22158358
TI  - Sarbanes-Oxley overburdens biotech companies.

PMID- 22158359
TI  - What's fueling the biotech engine--2010 to 2011.

PMID- 22158360
TI  - Agricultural microbial resources: private property or global commons?

PMID- 22158362
TI  - Dissecting cancer heterogeneity.

PMID- 22158364
TI  - The new landscape of protein ubiquitination.

PMID- 22158363
TI  - Genomic rearrangement in three dimensions.

PMID- 22158370
TI  - The challenges of modern interdisciplinary medical research.

PMID- 22158376
TI  - Diagnostic imaging: A new dawn for CT scans in colon screening?

PMID- 22158377
TI  - Cancer: Mdm2-regulated stabilization of HuR by neddylation in HCC and colon
      cancer--a possible target for therapy.

PMID- 22158378
TI  - Pancreas: Histological diagnostic criteria for autoimmune pancreatitis.

PMID- 22158379
TI  - Gut microbiota: FUT2 genotype influences the gut microbiota in patients with
      Crohn's disease and healthy individuals.

PMID- 22158380
TI  - Diagnostic imaging: Probe-based confocal laser endomicroscopy aids the detection
      of residual colorectal neoplasia and small colorectal polyps.

PMID- 22158381
TI  - Neurogastroenterology in 2011: Emerging concepts in neurogastroenterology and
      motility.

PMID- 22158382
TI  - Colorectal cancer: A single-cell snapshot of gene expression in healthy and
      cancerous colon tissue.

PMID- 22158384
TI  - Helicobacter pylori: Bone-marrow-derived cells could cause gastric preneoplasia
      in chronic Helicobacter pylori infection.

PMID- 22158385
TI  - Infection: Spironolactone and increased mortality.

PMID- 22158386
TI  - Allogeneic hematopoietic SCT in patients with AML following
      treosulfan/fludarabine conditioning.
AB  - An alternative reduced-toxicity conditioning regimen for allogeneic
      transplantation, based on treosulfan and fludarabine, has recently been
      identified. The safety and efficacy of this new conditioning regimen has been
      investigated prospectively in patients with AML. A total number of 75 patients
      with AML in CR were treated with 3 * 14 g/m(2) treosulfan and 5 * 30 mg/m(2)
      fludarabine, followed by matched sibling or unrelated SCT. Patients were
      evaluated for engraftment, adverse events, GVHD, and for non-relapse mortality,
      relapse incidence, overall and disease-free survival (DFS). All patients showed
      primary engraftment of neutrophils after a median of 20 days. Non-hematological
      adverse events grade III-IV in severity included mainly infections (59%) and
      gastrointestinal symptoms (7%). Acute GVHD grade II-IV occurred in 21% and
      extensive chronic GVHD occurred in 16% of the patients. After a median follow-up
      of 715 days, the 2-year overall and DFS estimates were 61% and 55%, respectively.
      The 2-year incidences of relapse and non-relapse mortality reached 34% and 11%,
      respectively. In summary, our data confirm promising safety and efficacy of the
      treosulfan-based conditioning therapy in AML patients, ClinicalTrials.gov
      Identifier: NCT01063660.

PMID- 22158387
TI  - Secondary MGUS after autologous hematopoietic progenitor cell transplantation in
      plasma cell myeloma: a matter of undetermined significance.
AB  - Plasma cell myeloma, characterized by clonally aberrant plasma cells that produce
      abnormal monoclonal Igs, is the most common indication for autologous
      hematopoietic progenitor cell transplantation (AHPCT) in North America. We
      observed appearance of new monoclonal gammopathies different from the original
      protein in the post-AHPCT setting and termed this condition 'secondary MGUS'
      (monoclonal gammopathy of undetermined significance). Hence, we performed a
      retrospective, single institution review of serum protein
      electrophoresis/immunofixation electrophoresis data in 92 AHPCT recipients from
      the period 2000-2009. In all, 22 of 92 patients (24%) undergoing AHPCT met
      criteria for secondary MGUS. Contrary to previous studies, often referred to as
      'abnormal protein banding,' we did not observe this condition as a favorable
      prognostic indicator in affected patients when compared with the control group
      (P=0.686). However, we did note that a subgroup of the study cohort who developed
      secondary MGUS after a prolonged latency (>10 months) had an improved median OS
      compared with the remainder of the study cohort (75 months vs 41 months,
      P=0.005). As there have been significant advancements in understanding the
      pathobiology and clinical significance of MGUS, we believe that secondary MGUS
      merits dedication of resources for investigation to determine its true clinical
      relevance, prognostic value and pathophysiology.

PMID- 22158388
TI  - Long-term follow-up of HCV-infected hematopoietic SCT patients and effects of
      antiviral therapy.
AB  - This prospective study was initiated in 1993 with the aim to study late effects
      and responses to antiviral therapy in a cohort of hepatitis C virus (HCV)
      infected patients. A total of 195 patients were included from 12 centers. In all,
      134 patients had undergone allogeneic and 61 autologous hematopoietic SCT (HSCT).
      The median follow-up from HSCT is currently 16.8 years and the maximum 27.2
      years. Overall 33 of 195 patients have died of which 6 died from liver
      complications. The survival probability was 81.6% and the cumulative incidence
      for death in liver complications was 6.1% at 20 years after HSCT. The cumulative
      incidence of severe liver complications (death from liver failure, cirrhosis and
      liver transplantation) was 11.7% at 20 years after HSCT. In all, 85 patients have
      been treated with IFN; 42 in combination with ribavirin. The sustained response
      rate was 40%. The rates of severe side effects were comparable to other patient
      populations and no patient developed significant exacerbations of GVHD. Patients
      receiving antiviral therapy had a trend toward a decreased risk of severe liver
      complications (odds ratio=0.33; P=0.058). HCV infection is associated with
      morbidity and mortality in long-term survivors after HSCT. Antiviral therapy can
      be given safely and might reduce the risk for severe complications.

PMID- 22158389
TI  - Osteonecrosis in children after allogeneic hematopoietic cell transplantation:
      study of prevalence, risk factors and longitudinal changes using MR imaging.
AB  - Osteonecrosis after hematopoietic SCT (HCT) has seldom been addressed in
      pediatric populations. At our institution, since January 2002, children
      undergoing allogeneic HCT (alloHCT) receive yearly follow-up magnetic resonance
      imaging (MR) of hips and knees. To estimate the prevalence, longitudinal changes
      and associated risk factors for osteonecrosis after alloHCT, we reviewed MRs for
      children who underwent single alloHCT during the study period. We analyzed 149 of
      344 patients who had post-HCT MR imaging performed (84 males; median age 11 years
      (range, 0.5-21 years)), median follow-up time was 32.6 months (range, 2.8-97.2
      months). In all, 44 (29.5%) developed osteonecrosis of hips and/or knees; of
      those, 20 (45%) had at least 30% epiphyseal involvement. In 23 (52%),
      osteonecrosis lesions were identified in the first and in 43 (98%) by the third
      yearly scan. Knees were more frequently involved than hips; severity of
      osteonecrosis was greater in hips. Those who had pre-alloHCT osteonecrosis, two
      patients' hips and six patients' knees resolved completely; three patients'
      osteonecrosis lesions regressed after alloHCT. On risk factor analysis, age at
      time of alloHCT (P=0.051) and osteonecrosis identified by MRs before alloHCT
      (P=0.001) were the primary risk factors. This analysis shows that preventive
      strategies for osteonecrosis in this population should focus on measures to
      minimize risk factors before alloHCT.

PMID- 22158391
TI  - Bacterial community dynamics in the hyporheic zone of an intermittent stream.
AB  - The dynamics of in situ bacterial communities in the hyporheic zone of an
      intermittent stream were described in high spatiotemporal detail. We assessed
      community dynamics in stream sediments and interstitial pore water over a two
      year period using terminal-restriction fragment length polymorphism. Here, we
      show that sediments remained saturated despite months of drought and limited
      hydrologic connectivity. The intermittency of stream surface water affected
      interstitial pore water communities more than hyporheic sediment communities.
      Seasonal changes in bacterial community composition was significantly associated
      with water intermittency, phosphate concentrations, temperature, nitrate and
      dissolved organic carbon (DOC) concentrations. During periods of low- to no
      surface water, communities changed from being rich in operational taxonomic units
      (OTUs) in isolated surface pools, to a few OTUs overall, including an overall
      decline in both common and rare taxa. Individual OTUs were compared between
      porewater and sediments. A total of 19% of identified OTUs existed in both
      porewater and sediment samples, suggesting that bacteria use hyporheic sediments
      as a type of refuge from dessication, transported through hydrologically
      connected pore spaces. Stream intermittency impacted bacterial diversity on rapid
      timescales (that is, within days), below-ground and in the hyporheic zone. Owing
      to the coupling of intermittent streams to the surrounding watershed, we stress
      the importance of understanding connectivity at the pore scale, consequences for
      below-ground and above-ground biodiversity and nutrient processing, and across
      both short- and long-time periods (that is, days to months to years).

PMID- 22158390
TI  - [Final results from four clinical studies in the field of cardiovascular diseases
      integrated in the "Mattoni del SSN - Mattone Outcome" Project].
AB  - Observational outcome studies represent a valid approach to evaluating
      comparative treatment effectiveness in real populations. The main objective of
      outcome research is to underline what works and what does not work in the field
      of health assistance. In 2004 the Italian Ministry of Health launched the Project
      "Mattone Misura dell'Outcome" aimed at assessing the introduction of procedures
      and methods for the systematic evaluation of outcomes in the national health
      system. A new experience, the PROGRESSI program (PROGRamma ESiti per SIVeAS e
      LEA), started in 2008 with the aim to further develop the methodologies for
      outcome evaluation. In this Supplement the final results from four clinical
      studies named "Sperimentazioni dell'area cardiovascolare del Progetto Mattoni"
      are presented. These studies started between 2005 and 2007 and their main
      objectives were to evaluate: --the contribution of information from current
      informative systems and clinical studies in risk-adjustment methodologies; --the
      advisability of introducing some clinical items in current informative systems to
      improve outcome estimates; --the goodness of follow-up procedures from current
      informative systems; and --the role of disease registries in the validation of
      comparative evaluation measures. The four studies were designed as voluntary
      prospective multicentre studies. Results concerning the characteristics of the
      enrolled populations as well as the risk-adjustment models built using
      information from current informative systems and/or clinical information are
      presented. As expected, each study produced specific remarks both in terms of
      clinical findings and contribution of different informative systems to the risk
      adjustment models. In general, models built with information from both current
      informative systems and clinical information show the best performance. Findings
      from these analyses will provide the public health system with suitable
      indications to improve statistical methodologies for outcome estimates.

PMID- 22158392
TI  - Temperature regulation of virulence factors in the pathogen Vibrio
      coralliilyticus.
AB  - Sea surface temperatures (SST) are rising because of global climate change. As a
      result, pathogenic Vibrio species that infect humans and marine organisms during
      warmer summer months are of growing concern. Coral reefs, in particular, are
      already experiencing unprecedented degradation worldwide due in part to
      infectious disease outbreaks and bleaching episodes that are exacerbated by
      increasing SST. For example, Vibrio coralliilyticus, a globally distributed
      bacterium associated with multiple coral diseases, infects corals at temperatures
      above 27  degrees C. The mechanisms underlying this temperature-dependent
      pathogenicity, however, are unknown. In this study, we identify potential
      virulence mechanisms using whole genome sequencing of V. coralliilyticus ATCC
      (American Type Culture Collection) BAA-450. Furthermore, we demonstrate direct
      temperature regulation of numerous virulence factors using proteomic analysis and
      bioassays. Virulence factors involved in motility, host degradation, secretion,
      antimicrobial resistance and transcriptional regulation are upregulated at the
      higher virulent temperature of 27  degrees C, concurrent with phenotypic changes
      in motility, antibiotic resistance, hemolysis, cytotoxicity and bioluminescence.
      These results provide evidence that temperature regulates multiple virulence
      mechanisms in V. coralliilyticus, independent of abundance. The ecological and
      biological significance of this temperature-dependent virulence response is
      reinforced by climate change models that predict tropical SST to consistently
      exceed 27  degrees C during the spring, summer and fall seasons. We propose V.
      coralliilyticus as a model Gram-negative bacterium to study temperature-dependent
      pathogenicity in Vibrio-related diseases.

PMID- 22158394
TI  - Temporal variation of beta-diversity and assembly mechanisms in a bacterial
      metacommunity.
AB  - The turnover of community composition across space, beta-diversity, is influenced
      by different assembly mechanisms, which place varying weight on local habitat
      factors, such as environmental conditions and species interactions, and regional
      factors such as dispersal and history. Several assembly mechanisms may function
      simultaneously; however, little is known about how their importance changes over
      time and why. Here, we implemented a field survey where we sampled a bacterial
      metacommunity consisting of 17 rock pools located at the Swedish Baltic Sea coast
      at 11 occasions during 1 year. We determined to which extent communities were
      structured by different assembly mechanisms using variation partitioning and
      studied changes in beta-diversity across environmental gradients over time. beta
      Diversity was highest at times of high overall productivity and environmental
      heterogeneity in the metacommunity, at least partly due to species sorting, that
      is, selection of taxa by the prevailing environmental conditions. In contrast,
      dispersal-driven assembly mechanisms were primarily detected at times when beta
      diversity was relatively low. There were no indications for strong and persistent
      differences in community composition or beta-diversity between permanent and
      temporary pools, indicating that the physical disturbance regime is of relatively
      minor importance. In summary, our study clearly suggests that there are temporal
      differences in the relative importance of different assembly mechanisms related
      to abiotic factors and shows that the temporal variability of those factors is
      important for a more complete understanding of bacterial metacommunity dynamics.

PMID- 22158393
TI  - Evidence of a robust resident bacteriophage population revealed through analysis
      of the human salivary virome.
AB  - Viruses are the most abundant known infectious agents on the planet and are
      significant drivers of diversity in a variety of ecosystems. Although there have
      been numerous studies of viral communities, few have focused on viruses within
      the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral
      particles and compared them with 263 516 bacterial 16S rRNA gene sequences from
      the saliva of five healthy human subjects over a 2- to 3-month period, in order
      to improve our understanding of the role viruses have in the complex oral
      ecosystem. Our data reveal viral communities in human saliva dominated by
      bacteriophages whose constituents are temporally distinct. The preponderance of
      shared homologs between the salivary viral communities in two unrelated subjects
      in the same household suggests that environmental factors are determinants of
      community membership. When comparing salivary viromes to those from human stool
      and the respiratory tract, each group was distinct, further indicating that
      habitat is of substantial importance in shaping human viromes. Compared with
      coexisting bacteria, there was concordance among certain predicted host-virus
      pairings such as Veillonella and Streptococcus, whereas there was discordance
      among others such as Actinomyces. We identified 122 728 virulence factor
      homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic
      gene function in the oral environment. That the vast majority of human oral
      viruses are bacteriophages whose putative gene function signifies some have a
      prominent role in lysogeny, suggests these viruses may have an important role in
      helping shape the microbial diversity in the human oral cavity.

PMID- 22158395
TI  - High-throughput isotopic analysis of RNA microarrays to quantify microbial
      resource use.
AB  - Most microorganisms remain uncultivated, and typically their ecological roles
      must be inferred from diversity and genomic studies. To directly measure
      functional roles of uncultivated microbes, we developed Chip-stable isotope
      probing (SIP), a high-sensitivity, high-throughput SIP method performed on a
      phylogenetic microarray (chip). This approach consists of microbial community
      incubations with isotopically labeled substrates, hybridization of the extracted
      community rRNA to a microarray and measurement of isotope incorporation--and
      therefore substrate use--by secondary ion mass spectrometer imaging (NanoSIMS).
      Laboratory experiments demonstrated that Chip-SIP can detect isotopic enrichment
      of 0.5 atom % (13)C and 0.1 atom % (15)N, thus permitting experiments with short
      incubation times and low substrate concentrations. We applied Chip-SIP analysis
      to a natural estuarine community and quantified amino acid, nucleic acid or fatty
      acid incorporation by 81 distinct microbial taxa, thus demonstrating that
      resource partitioning occurs with relatively simple organic substrates. The Chip
      SIP approach expands the repertoire of stable isotope-enabled methods available
      to microbial ecologists and provides a means to test genomics-generated
      hypotheses about biogeochemical function in any natural environment.

PMID- 22158396
TI  - Determinants of variations in coronary revascularization practices.
AB  - BACKGROUND: The ratio of percutaneous coronary interventions to coronary artery
      bypass graft surgeries (PCI:CABG ratio) varies considerably across hospitals. We
      conducted a comprehensive study to identify clinical and nonclinical factors
      associated with variations in the ratio across 17 cardiac centres in the province
      of Ontario. METHODS: In this retrospective cohort study, we selected a population
      based sample of 8972 patients who underwent an index cardiac catheterization
      between April 2006 and March 2007 at any of 17 hospitals that perform invasive
      cardiac procedures in the province. We classified the hospitals into four groups
      by PCI:CABG ratio (low [< 2.0], low-medium [2.0-2.7], medium-high [2.8-3.2] and
      high [> 3.2]). We explored the relative contribution of patient, physician and
      hospital factors to variations in the likelihood of patients receiving PCI or
      CABG surgery within 90 days after the index catheterization. RESULTS: The mean
      PCI:CABG ratio was 2.7 overall. We observed a threefold variation in the ratios
      across the four hospital ratio groups, from a mean of 1.6 in the lowest ratio
      group to a mean of 4.6 in the highest ratio group. Patients with single-vessel
      disease usually received PCI (88.4%-99.0%) and those with left main artery
      disease usually underwent CABG (80.8%-94.2%), regardless of the hospital's
      procedure ratio. Variation in the management of patients with non-emergent
      multivessel disease accounted for most of the variation in the ratios across
      hospitals. The mode of revascularization largely reflected the recommendation of
      the physician performing the diagnostic catheterization and was also influenced
      by the revascularization "culture" at the treating hospital. INTERPRETATION: The
      physician performing the diagnostic catheterization and the treating hospital
      were strong independent predictors of the mode of revascularization.
      Opportunities exist to improve transparency and consistency around the decision
      making process for coronary revascularization, most notably among patients with
      non-emergent multivessel disease.

PMID- 22158397
TI  - Overestimation of risk ratios by odds ratios in trials and cohort studies:
      alternatives to logistic regression.

PMID- 22158398
TI  - The studies that launched a thousand snips.

PMID- 22158399
TI  - Addiction is a disease: we must change our attitudes toward addicts.

PMID- 22158400
TI  - Pancreatic panniculitis.

PMID- 22158401
TI  - Treatment-refractory hypothyroidism.

PMID- 22158403
TI  - Hospital-induced delirium hits hard.

PMID- 22158405
TI  - Revascularization options: one size does not fit all.

PMID- 22158406
TI  - Genetic tests for athletic ability: science or snake oil?

PMID- 22158407
TI  - Ontario college beats retreat on alternative therapies.

PMID- 22158409
TI  - Food aid for children woefully substandard.

PMID- 22158408
TI  - The basis for monitoring strategies in clinical guidelines: a case study of
      prostate-specific antigen for monitoring in prostate cancer.
AB  - BACKGROUND: The volume of published literature on the evaluation and use of tests
      for monitoring purposes is sparse. Our aim was to determine the extent to which
      recommendations for monitoring prostate-specific antigen to detect recurrent
      prostate cancer consider key factors that should inform rule-based strategies for
      monitoring. METHODS: We reviewed the recommendations made in clinical guidelines
      for the repeated measurement of prostate-specific antigen in men who have
      received primary treatment for localized prostate cancer. We assessed the
      guidelines using the Appraisal of Guidelines for Research and Evaluation
      Framework. RESULTS: We identified guidelines and statements of best practice from
      nine organizations. We saw considerable inconsistency in recommendations for
      testing for prostate-specific antigen as a form of monitoring. Recommendations on
      when to test appeared to be almost exclusively determined using standard follow
      up schedules rather than any scientific basis. Recommendations on when to take
      action were primarily based on consensus statements or retrospective case series.
      Eight of the nine guidelines acknowledged the potential presence of measurement
      variability, but they did not attempt to account for the effect of such
      variability on the interpretation of the results of tests for prostate-specific
      antigen. Many recommendations were made with few or no supporting references;
      however, a variety of papers were cited across guidelines. Of 48 papers cited,
      29.1% (14/48) were reviews; the remaining 70.8% (34/48) of papers cited were
      primary studies. INTERPRETATION: A systematic approach to the development of
      monitoring schedules using prostate-specific antigen in guidelines for prostate
      cancer is lacking, due to inadequacies in the available evidence and its use.

PMID- 22158410
TI  - Cost-effective method for microbial source tracking using specific human and
      animal viruses.
AB  - Microbial contamination of the environment represents a significant health risk.
      Classical bacterial fecal indicators have shown to have significant limitations,
      viruses are more resistant to many inactivation processes and standard fecal
      indicators do not inform on the source of contamination. The development of cost
      effective methods for the concentration of viruses from water and molecular
      assays facilitates the applicability of viruses as indicators of fecal
      contamination and as microbial source tracking (MST) tools. Adenoviruses and
      polyomaviruses are DNA viruses infecting specific vertebrate species including
      humans and are persistently excreted in feces and/or urine in all geographical
      areas studied. In previous studies, we suggested the quantification of human
      adenoviruses (HAdV) and JC polyomaviruses (JCPyV) by quantitative PCR (qPCR) as
      an index of human fecal contamination. Recently, we have developed qPCR assays
      for the specific quantification of porcine adenoviruses (PAdV) and bovine
      polyomaviruses (BPyV) as animal fecal markers of contamination with sensitivities
      of 1-10 genome copies per test tube. In this study, we present the procedure to
      be followed to identify the source of contamination in water samples using these
      tools. As example of representative results, analysis of viruses in ground water
      presenting high levels of nitrates is shown. Detection of viruses in low or
      moderately polluted waters requires the concentration of the viruses from at
      least several liters of water into a much smaller volume, a procedure that
      usually includes two concentration steps in series. This somewhat cumbersome
      procedure and the variability observed in viral recoveries significantly hamper
      the simultaneous processing of a large number of water samples. In order to
      eliminate the bottleneck caused by the two-step procedures we have applied a one
      step protocol developed in previous studies and applicable to a diversity of
      water matrices. The procedure includes: acidification of ten-liter water samples,
      flocculation by skimmed milk, gravity sedimentation of the flocculated materials,
      collection of the precipitate and centrifugation, resuspension of the precipitate
      in 10 ml phosphate buffer. The viral concentrate is used for the extraction of
      viral nucleic acids and the specific adenoviruses and polyomaviruses of interest
      are quantified by qPCR. High number of samples may be simultaneously analyzed
      using this low-cost concentration method. The procedure has been applied to the
      analysis of bathing waters, seawater and river water and in this study, we
      present results analyzing groundwater samples. This high-throughput quantitative
      method is reliable, straightforward, and cost-effective.

PMID- 22158411
TI  - The impact of perinatal immune development on mucosal homeostasis and chronic
      inflammation.
AB  - The mucosal surfaces of the gut and airways have important barrier functions and
      regulate the induction of immunological tolerance. The rapidly increasing
      incidence of chronic inflammatory disorders of these surfaces, such as
      inflammatory bowel disease and asthma, indicates that the immune functions of
      these mucosae are becoming disrupted in humans. Recent data indicate that events
      in prenatal and neonatal life orchestrate mucosal homeostasis. Several
      environmental factors promote the perinatal programming of the immune system,
      including colonization of the gut and airways by commensal microorganisms. These
      complex microbial-host interactions operate in a delicate temporal and spatial
      manner and have an important role in the induction of homeostatic mechanisms.

PMID- 22158413
TI  - Innate immunity: TLR9 mutations reveal a new level of self tolerance.

PMID- 22158412
TI  - The role of ubiquitylation in immune defence and pathogen evasion.
AB  - Ubiquitylation is a widely used post-translational protein modification that
      regulates many biological processes, including immune responses. The role of
      ubiquitin in immune regulation was originally uncovered through studies of
      antigen presentation and the nuclear factor-kappaB family of transcription
      factors, which orchestrate host defence against microorganisms. Recent studies
      have revealed crucial roles of ubiquitylation in many aspects of the immune
      system, including innate and adaptive immunity and antimicrobial autophagy. In
      addition, mounting evidence indicates that microbial pathogens exploit the
      ubiquitin pathway to evade the host immune system. Here, we review recent
      advances on the role of ubiquitylation in host defence and pathogen evasion.

PMID- 22158415
TI  - Regulatory T cells: Practise makes perfect.

PMID- 22158414
TI  - Molecular programming of B cell memory.
AB  - The development of high-affinity B cell memory is regulated through three
      separable phases, each involving antigen recognition by specific B cells and
      cognate T helper cells. Initially, antigen-primed B cells require cognate T cell
      help to gain entry into the germinal centre pathway to memory. Once in the
      germinal centre, B cells with variant B cell receptors must access antigens and
      present them to germinal centre T helper cells to enter long-lived memory B cell
      compartments. Following antigen recall, memory B cells require T cell help to
      proliferate and differentiate into plasma cells. A recent surge of information -
      resulting from dynamic B cell imaging in vivo and the elucidation of T follicular
      helper cell programmes - has reshaped the conceptual landscape surrounding the
      generation of memory B cells. In this Review, we integrate this new information
      about each phase of antigen-specific B cell development to describe the newly
      unravelled molecular dynamics of memory B cell programming.

PMID- 22158416
TI  - Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase
      activity.
AB  - Protein sulfenylation is a post-translational modification of emerging importance
      in higher eukaryotes. However, investigation of its diverse roles remains
      challenging, particularly within a native cellular environment. Herein we report
      the development and application of DYn-2, a new chemoselective probe for
      detecting sulfenylated proteins in human cells. These studies show that epidermal
      growth factor receptor-mediated signaling results in H(2)O(2) production and
      oxidation of downstream proteins. In addition, we demonstrate that DYn-2 has the
      ability to detect differences in sulfenylation rates within the cell, which are
      associated with differences in target protein localization. We also show that the
      direct modification of epidermal growth factor receptor by H(2)O(2) at a critical
      active site cysteine (Cys797) enhances its tyrosine kinase activity.
      Collectively, our findings reveal sulfenylation as a global signaling mechanism
      that is akin to phosphorylation and has regulatory implications for other
      receptor tyrosine kinases and irreversible inhibitors that target oxidant
      sensitive cysteines in proteins.

PMID- 22158417
TI  - The death domain-containing protein Unc5CL is a novel MyD88-independent activator
      of the pro-inflammatory IRAK signaling cascade.
AB  - The family of death domain (DD)-containing proteins are involved in many cellular
      processes, including apoptosis, inflammation and development. One of these
      molecules, the adapter protein MyD88, is a key factor in innate and adaptive
      immunity that integrates signals from the Toll-like receptor/interleukin (IL)-1
      receptor (TLR/IL-1R) superfamily by providing an activation platform for IL-1R
      associated kinases (IRAKs). Here we show that the DD-containing protein Unc5CL
      (also known as ZUD) is involved in a novel MyD88-independent mode of IRAK
      signaling that culminates in the activation of the transcription factor nuclear
      factor kappa B (NF-kappaB) and c-Jun N-terminal kinase. Unc5CL required IRAK1,
      IRAK4 and TNF receptor-associated factor 6 but not MyD88 for its ability to
      activate these pathways. Interestingly, the protein is constitutively
      autoproteolytically processed, and is anchored by its N-terminus specifically to
      the apical face of mucosal epithelial cells. Transcriptional profiling identified
      mainly chemokines, including IL-8, CXCL1 and CCL20 as Unc5CL target genes. Its
      prominent expression in mucosal tissues, as well as its ability to induce a pro
      inflammatory program in cells, suggests that Unc5CL is a factor in epithelial
      inflammation and immunity as well as a candidate gene involved in mucosal
      diseases such as inflammatory bowel disease.

PMID- 22158418
TI  - Chk2 mediates RITA-induced apoptosis.
AB  - Reactivation of the p53 tumor-suppressor protein by small molecules like Nutlin-3
      and RITA (reactivation of p53 and induction of tumor cell apoptosis) is a
      promising strategy for cancer therapy. The molecular mechanisms involved in the
      responses to RITA remain enigmatic. Several groups reported the induction of a
      p53-dependent DNA damage response. Furthermore, the existence of a p53-dependent
      S-phase checkpoint has been suggested, involving the checkpoint kinase Chk1. We
      have recently shown synergistic induction of apoptosis by RITA in combination
      with Nutlin-3, and we observed concomitant Chk2 phosphorylation. Therefore, we
      investigated whether Chk2 contributes to the cellular responses to RITA.
      Strikingly, the induction of apoptosis seemed entirely Chk2 dependent.
      Transcriptional activity of p53 in response to RITA required the presence of
      Chk2. A partial rescue of apoptosis observed in Noxa knockdown cells emphasized
      the relevance of p53 transcriptional activity for RITA-induced apoptosis. In
      addition, we observed an early p53- and Chk2-dependent block of DNA replication
      upon RITA treatment. Replicating cells seemed more prone to entering RITA-induced
      apoptosis. Furthermore, the RITA-induced DNA damage response, which was not a
      secondary effect of apoptosis induction, was strongly attenuated in cells lacking
      p53 or Chk2. In conclusion, we identified Chk2 as an essential mediator of the
      cellular responses to RITA.

PMID- 22158420
TI  - [Beyond glycemic control in type 2 diabetes. Promises and gambles of therapy with
      glucagon-like peptide-1 receptor agonists].

PMID- 22158419
TI  - Regulation of skin aging and heart development by TAp63.
AB  - Since the discovery of the TP63 gene in 1998, many studies have demonstrated that
      DeltaNp63, a p63 isoform of the p53 gene family, is involved in multiple
      functions during skin development and in adult stem/progenitor cell regulation.
      In contrast, TAp63 studies have been mostly restricted to its apoptotic function
      and more recently as the guardian of oocyte integrity. TAp63 endogenous
      expression is barely detectable in embryos and adult (except in oocytes),
      presumably because of its rapid degradation and the lack of antibodies able to
      detect weak expression. Nevertheless, two recent independent studies have
      demonstrated novel functions for TAp63 that could have potential implications to
      human pathologies. The first discovery is related to the protective role of TAp63
      on premature aging. TAp63 controls skin homeostasis by maintaining dermal and
      epidermal progenitor/stem cell pool and protecting them from senescence, DNA
      damage and genomic instability. The second study is related to the role of TAp63,
      expressed by the primitive endoderm, on heart development. This unexpected role
      for TAp63 has been discovered by manipulation of embryonic stem cells in vitro
      and confirmed by the severe cardiomyopathy observed in brdm2 p63-null embryonic
      hearts. Interestingly, in both cases, TAp63 acts in a cell-nonautonomous manner
      on adjacent cells. Here, we discuss these findings and their potential connection
      during development.

PMID- 22158421
TI  - [Protective effects of glucagon-like peptide-1 on beta-cells: preclinical and
      clinical data].
AB  - Dipartimento di Medicina Interna e Scienze dell'Invecchiamento, Universita degli
      Studi "G. d'Annunzio", Chieti Continuing b-cell mass and function loss represents
      the key mechanism for the pathogenesis and the progression of type 2 diabetes
      mellitus. Drugs capable of arresting b-cell loss and eventually able to bring b
      cell function close to be back to normal would then be a formidable help in type
      2 diabetes mellitus treatment. The glucagon-like peptide-1 (GLP-1) receptor
      agonists exenatide and liraglutide can stimulate in vitro neogenesis and prevent
      apoptosis in b-cell-like cell lines. Consistently, treatment with GLP-1 receptor
      agonists ameliorates glucose metabolism, preserves b-cell mass and improves b
      cell function in several animal models of diabetes. For instance, in the db/db
      mice, liraglutide protects the b-cell from oxidative stress and endoplasmic
      reticulum stress-related damage. Data in humans, in vivo, are less definitive and
      often based on scarcely reliable indexes of b-cell function. However, short-term
      treatment (14 weeks) with liraglutide increased b-cell maximal response capacity
      in a dose-response fashion. A longer (1 year) exenatide treatment also was able
      to increase b-cell maximal response capacity, but the effect was no longer there
      after a 4-week washout period. However, a marginal, although significant as
      compared to glargine treatment, improvement in another b-cell function index
      (disposition index) was observed after a 4-week washout period following 3-year
      exenatide treatment. Finally, although no clinical trials with a long enough
      follow-up period are presently available, durable glucose control has been
      obtained during 2 years of liraglutide treatment in monotherapy. Since the
      durability of good control is strictly dependent upon a lack of further b-cell
      function deterioration, these clinical data may foster hope that GLP-1 receptor
      antagonist treatment might help preserving b-cell function also in individuals
      affected by type 2 diabetes mellitus.

PMID- 22158422
TI  - [Effects of glucagon-like peptide-1 on appetite and body weight: preclinical and
      clinical data].
AB  - Obesity is associated with an increased risk of developing type 2 diabetes and
      cardiovascular disease. Pharmacological treatments of diabetes are mostly
      associated with weight gain, an undesirable event due to the fact that an
      increase in adiposity, especially visceral, is associated with reduced insulin
      sensitivity, worse cardiovascular risk profile and decreased adherence to
      treatment. Analogues of glucagon-like peptide-1 (GLP-1) represent a new
      therapeutic option for type 2 diabetes, which offer the advantage of combining
      beneficial effects on metabolic control with a significant reduction in body
      weight. In this review, we discuss data of preclinical studies and clinical
      trials that evaluated the effects of liraglutide and exenatide, the two analogues
      of GLP-1 currently available in Italy, on body weight.

PMID- 22158423
TI  - [Cardioprotective effects of glucagon-like peptide-1: preclinical and clinical
      data].
AB  - The glucagon-like peptide-1 (GLP-1) is a 30 amino acid incretin hormone
      synthesized by L cells of ileum and colon in response to a meal. Once secreted,
      it is rapidly inactivated by specific enzymes called dipeptidyl dipeptidase 4.
      The main actions of GLP-1 are (i) to stimulate insulin secretion; (ii) to inhibit
      glucagon secretion; (iii) to elicit a delay of gastric emptying time; and (iv) to
      stimulate neogenesis of insulin-secreting cells. Patients with type 2 diabetes
      show low GLP-1 concentrations in response to a meal, making treatment with
      incretin mimetics specifically indicated in this patient subset. Besides these
      effects on intermediary metabolism, GLP-1 also plays an important role in the
      cardiovascular system by reducing blood pressure, improving endothelial function,
      and increasing myocardial contractility. These mechanisms of action will be
      discussed in detail in this article.

PMID- 22158424
TI  - CAPN3 mRNA processing alteration caused by splicing mutation associated with
      novel genomic rearrangement of Alu elements.
AB  - Recessive mutations of CAPN3 gene are reported to be responsible for limb girdle
      muscular dystrophy type 2A (LGMD2A). In all, 15-25% of intronic nucleotide
      changes identified in this gene were investigated by in silico analysis, but
      occasionally supported by experimental data or reported in some cases as a
      polymorphism. We report here genetic and transcriptional analyses in three
      Tunisian patients belonging to the same consanguineous family sharing the same
      mutation c.1194-9 A>G and Alu repeats insertion in intron 7 of CAPN3 gene.
      Reverse transcriptase-PCR experiments performed on total RNA from the patient's
      muscle biopsy showed retention of the eight last nucleotides of intron 9 in the
      CAPN3 transcript lacking the first seven exons. Our results provide evidence
      regarding the potential involvement of Alu elements in aberrant processing of pre
      mRNA owing to the disruption of pre-existing intronic splicing regulatory
      elements. We also demonstrated variable mRNA alternative splicing among tissues
      and between LGMD2A patients. A deep intronic variation and rearrangement have
      been reported in the literature as causing genetic diseases in humans. However,
      this is the first report on a potential pathogenic CAPN3 gene mutation resulting
      from an Alu insertion.

PMID- 22158425
TI  - Genome-wide linkage analysis in families with infantile hypertrophic pyloric
      stenosis indicates novel susceptibility loci.
AB  - Infantile hypertrophic pyloric stenosis (IHPS) is a common cause of upper
      gastrointestinal obstruction during infancy. A multifactorial background of the
      disease is well established. Multiple susceptibility loci including the neuronal
      nitric oxide synthase (NOS1) gene have previously been linked to IHPS, but
      contradictory results of linkage studies in different materials indicate genetic
      heterogeneity. To identify IHPS susceptibility loci, we conducted a genome-wide
      linkage analysis in 37 Swedish families. In regions where the Swedish material
      showed most evidence in favor of linkage, 31 additional British IHPS families
      were analyzed. Evidence in favor of significant linkage was observed in the
      Swedish material to two loci on chromosome 2q24 (non-parametric linkage (NPL)
      =3.77) and 7p21 (NPL=4.55). In addition, evidence of suggestive linkage was found
      to two loci on chromosome 6p21 (NPL=2.97) and 12q24 (NPL=2.63). Extending the
      material with British samples did not enhance the level of significance. Regions
      with linkage harbor interesting candidate genes, such as glucagon-like peptide-2
      (GLP-2 encoded by the glucagon gene GCG), NOS1, motilin (MLN) and neuropeptide Y
      (NPY). The coding exons for GLP-2, and NPY were screened for mutations with
      negative results. In conclusion, we could confirm suggestive linkage to the
      region harboring the NOS1 gene and detected additional novel susceptibility loci
      for IHPS.

PMID- 22158426
TI  - Commentary on 'Functional analysis of APOE locus genetic variation implicates
      regional enhancers in the regulation of both TOMM40 and APOE'.

PMID- 22158427
TI  - A commentary on implication of gene copy number variation in health and diseases.

PMID- 22158428
TI  - Isolation of functional cardiac immune cells.
AB  - Cardiac immune cells are gaining interest for the roles they play in the
      pathological remodeling in many cardiac diseases. These immune cells, which
      include mast cells, T-cells and macrophages; store and release a variety of
      biologically active mediators including cytokines and proteases such as tryptase.
      These mediators have been shown to be key players in extracellular matrix
      metabolism by activating matrix metalloproteinases or causing collagen
      accumulation by modulating the cardiac fibroblasts' function. However, available
      techniques for isolating cardiac immune cells have been problematic because they
      use bacterial collagenase to digest the myocardial tissue. This technique causes
      activation of the immune cells and thus a loss of function. For example, cardiac
      mast cells become significantly less responsive to compounds that cause
      degranulation. Therefore, we developed a technique that allows for the isolation
      of functional cardiac immune cells which would lead to a better understanding of
      the role of these cells in cardiac disease. This method requires a familiarity
      with the anatomical location of the rat's xiphoid process, axilla and falciform
      ligament, and pericardium of the heart. These landmarks are important to increase
      success of the procedure and to ensure a higher yield of cardiac immune cells.
      These isolated cardiac immune cells can then be used for characterization of
      functionality, phenotype, maturity, and co-culture experiments with other cardiac
      cells to gain a better understanding of their interactions.

PMID- 22158429
TI  - Candida albicans morphogenesis and host defence: discriminating invasion from
      colonization.
AB  - Candida albicans is a common fungal pathogen of humans that colonizes the skin
      and mucosal surfaces of most healthy individuals. Until recently, little was
      known about the mechanisms by which mucosal antifungal defences tolerate
      colonizing C. albicans but react strongly when hyphae of the same microorganism
      attempt to invade tissue. In this Review, we describe the properties of yeast
      cells and hyphae that are relevant to their interaction with the host, and the
      immunological mechanisms that differentially recognize colonizing versus invading
      C. albicans.

PMID- 22158430
TI  - IAPs, TNF, inflammation and Jurg Tschopp; a personal perspective.

PMID- 22158432
TI  - Polarity and renal cystogenesis.

PMID- 22158434
TI  - Pyridoxamine, advanced glycation inhibition, and diabetic nephropathy.

PMID- 22158433
TI  - Comparative effects of angiotensin-converting enzyme inhibition and angiotensin
      receptor blockade on inflammation during hemodialysis.
AB  - Biomarkers of oxidative stress and inflammation predict cardiovascular events in
      maintenance hemodialysis patients. Angiotensin-converting enzyme (ACE) inhibitors
      and angiotensin-receptor blockers (ARBs) reduce cardiovascular mortality in the
      general population, but their benefit in maintenance hemodialysis patients is not
      fully explored. To test whether ACE inhibitors and ARBs differentially affect
      markers of oxidative stress, inflammation, and fibrinolysis during hemodialysis,
      we conducted a randomized, double-blind, placebo-controlled 3*3 crossover study.
      We randomly assigned 15 participants undergoing hemodialysis to placebo, ramipril
      (5 mg/d), and valsartan (160 mg/d) for 7 days, with a washout period of 3 weeks
      in between the treatments. On the morning of the seventh day of drug treatment,
      participants underwent serial blood sampling during hemodialysis. Neither
      ramipril nor valsartan affected BP during hemodialysis. Ramipril increased IL
      1beta concentrations (P=0.02) and decreased IL-10 concentrations (P=0.04)
      compared with placebo. Valsartan and ramipril both lowered IL-6 levels during
      dialysis (P<0.01 for each compared with placebo). Valsartan increased F(2)
      isoprostane levels, and ramipril suggested a similar trend (P=0.09). Valsartan
      and ramipril both lowered D-dimer levels (P<0.01 for both), whereas only ramipril
      seemed to prevent a rise in vWf levels (P=0.04). In summary, during hemodialysis,
      valsartan induces a greater anti-inflammatory effect compared with ramipril,
      although ramipril seems to prevent dialysis-induced endothelial dysfunction as
      measured by levels of vWf. A prospective clinical trial is necessary to determine
      whether ACE inhibitors and ARBs also differ with respect to their effects on
      cardiovascular mortality in this population.

PMID- 22158436
TI  - Bowman's beta-catenin.

PMID- 22158435
TI  - Outpatient nephrology referral rates after acute kidney injury.
AB  - AKI associates with an increased risk for the development and progression of CKD
      and mortality. Processes of care after an episode of AKI are not well described.
      Here, we examined the likelihood of nephrology referral among survivors of AKI at
      risk for subsequent decline in kidney function in a US Department of Veterans
      Affairs database. We identified 3929 survivors of AKI hospitalized between
      January 2003 and December 2008 who had an estimated GFR (eGFR) <60 ml/min per
      1.73 m(2) 30 days after peak injury. We analyzed time to referral considering
      improvement in kidney function (eGFR >=60 ml/min per 1.73 m(2)), dialysis
      initiation, and death as competing risks over a 12-month surveillance period.
      Median age was 73 years (interquartile range, 62-79 years) and the prevalence of
      preadmission kidney dysfunction (baseline eGFR <60 ml/min per 1.73 m(2)) was 60%.
      Overall mortality during the surveillance period was 22%. The cumulative
      incidence of nephrology referral before dying, initiating dialysis, or
      experiencing an improvement in kidney function was 8.5% (95% confidence interval,
      7.6-9.4). Severity of AKI did not affect referral rates. These data demonstrate
      that a minority of at-risk survivors are referred for nephrology care after an
      episode of AKI. Determining how to best identify survivors of AKI who are at
      highest risk for complications and progression of CKD could facilitate early
      nephrology-based interventions.

PMID- 22158437
TI  - Low-power nano-optical vortex trapping via plasmonic diabolo nanoantennas.
AB  - Optical vortex trapping can allow the capture and manipulation of micro- and
      nanometre-sized objects such as damageable biological particles or particles with
      a refractive index lower than the surrounding material. However, the quest for
      nanometric optical vortex trapping that overcomes the diffraction limit remains.
      Here we demonstrate the first experimental implementation of low-power nano
      optical vortex trapping using plasmonic resonance in gold diabolo nanoantennas.
      The vortex trapping potential was formed with a minimum at 170 nm from the
      central local maximum, and allowed polystyrene nanoparticles in water to be
      trapped strongly at the boundary of the nanoantenna. Furthermore, a large radial
      trapping stiffness, ~0.69 pN nm(-1) W(-1), was measured at the position of the
      minimum potential, showing good agreement with numerical simulations. This
      subwavelength-scale nanoantenna system capable of low-power trapping represents a
      significant step toward versatile, efficient nano-optical manipulations in lab-on
      a-chip devices.

PMID- 22158439
TI  - Migrating deformation in the Central Andes from enhanced orographic rainfall.
AB  - Active shortening in the Central Andes shifted from the western to the eastern
      margin between 10-7 Ma. Here we propose that this shift was primarily controlled
      by changes in erosion patterns. The uplift of the Andes blocked easterly winds,
      resulting in enhanced orographic rainfall on the eastern margin and reduced
      rainfall on the western margin. Lower erosion rates, associated with the arid
      conditions, caused the western margin to steepen inhibiting internal deformation
      and the migration of deformation to the eastern margin where it is active today.
      River channel profiles on the western margin are indicative of long-term
      transience from an older tectonic event whereas those on the eastern margin
      reflect ongoing coupled climatic-tectonic feedback. Both critical wedge theory
      and local-scale fault friction calculations support this interpretation. This
      work emphasizes the role that orographic rainfall and erosion can have on the
      orogen-scale development of mountain belts.

PMID- 22158438
TI  - O-linked-N-acetylglucosamine on extracellular protein domains mediates epithelial
      cell-matrix interactions.
AB  - The O-linked-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and
      nuclear proteins regulates basic cellular functions and is involved in the
      aetiology of diabetes and neurodegeneration. This intracellular O-GlcNAcylation
      is catalyzed by a single O-GlcNAc transferase, OGT. Here we report a novel OGT,
      EOGT, responsible for extracellular O-GlcNAcylation. Although both OGT and EOGT
      are regulated by hexosamine flux, EOGT localizes to the lumen of the endoplasmic
      reticulum and transfers GlcNAc to epidermal growth factor-like domains in an OGT
      independent manner. Loss of Eogt gives phenotypes similar to those caused by
      defects in the apical extracellular matrix. Dumpy (Dp), a membrane-anchored
      extracellular protein, is O-GlcNAcylated, and EOGT is required for Dp-dependent
      epithelial cell-matrix interactions. Thus, O-GlcNAcylation of secreted and
      membrane glycoproteins is a novel mediator of cell-cell or cell-matrix
      interactions at the cell surface.

PMID- 22158440
TI  - Rebalancing of internally generated carriers for mid-infrared interband cascade
      lasers with very low power consumption.
AB  - The interband cascade laser differs from any other class of semiconductor laser,
      conventional or cascaded, in that most of the carriers producing population
      inversion are generated internally, at semimetallic interfaces within each stage
      of the active region. Here we present simulations demonstrating that all previous
      interband cascade laser performance has suffered from a significant imbalance of
      electron and hole densities in the active wells. We further confirm
      experimentally that correcting this imbalance with relatively heavy n-type doping
      in the electron injectors substantially reduces the threshold current and power
      densities relative to all earlier devices. At room temperature, the redesigned
      devices require nearly two orders of magnitude less input power to operate in
      continuous-wave mode than the quantum cascade laser. The interband cascade laser
      is consequently the most attractive option for gas sensing and other
      spectroscopic applications requiring low output power and minimum heat
      dissipation at wavelengths extending from 3 MUm to beyond 6 MUm.

PMID- 22158441
TI  - Tandem synthesis of alternating polyesters from renewable resources.
AB  - The vast majority of commodity materials are obtained from petrochemical
      feedstocks. These resources will plausibly be depleted within the next 100 years,
      and the peak in global oil production is estimated to occur within the next few
      decades. In this regard, biomass represents an abundant carbon-neutral renewable
      resource for the production of polymers. Here we report a new strategy, based on
      tandem catalysis, to obtain renewable materials. Commercially available complexes
      are found to be efficient catalysts for alternating polyesters from the
      cyclization of dicarboxylic acids followed by alternating copolymerization of the
      resulting anhydrides with epoxides. This operationally simple method is an
      attractive strategy for the production of new biodegradable polyesters.

PMID- 22158442
TI  - Photon diffusion near the point-of-entry in anisotropically scattering turbid
      media.
AB  - From astronomy to cell biology, the manner in which light propagates in turbid
      media has been of central importance for many decades. However, light propagation
      near the point-of-entry in turbid media has never been analytically described,
      until now. Here we report a straightforward and accurate method that overcomes
      this longstanding, unsolved problem in radiative transport. Our theory properly
      treats anisotropic photon scattering events and takes the specific form of the
      phase function into account. As a result, our method correctly predicts the
      spatially dependent diffuse reflectance of light near the point-of-entry for any
      arbitrary phase function. We demonstrate that the theory is in excellent
      agreement with both experimental results and Monte Carlo simulations for several
      commonly used phase functions.

PMID- 22158443
TI  - Evolution of the base of the brain in highly encephalized human species.
AB  - The increase of brain size relative to body size-encephalization-is intimately
      linked with human evolution. However, two genetically different evolutionary
      lineages, Neanderthals and modern humans, have produced similarly large-brained
      human species. Thus, understanding human brain evolution should include research
      into specific cerebral reorganization, possibly reflected by brain shape changes.
      Here we exploit developmental integration between the brain and its underlying
      skeletal base to test hypotheses about brain evolution in Homo. Three-dimensional
      geometric morphometric analyses of endobasicranial shape reveal previously
      undocumented details of evolutionary changes in Homo sapiens. Larger olfactory
      bulbs, relatively wider orbitofrontal cortex, relatively increased and forward
      projecting temporal lobe poles appear unique to modern humans. Such brain
      reorganization, beside physical consequences for overall skull shape, might have
      contributed to the evolution of H. sapiens' learning and social capacities, in
      which higher olfactory functions and its cognitive, neurological behavioral
      implications could have been hitherto underestimated factors.

PMID- 22158444
TI  - Competitive and cooperative metabolic interactions in bacterial communities.
AB  - Revealing the ecological principles that shape communities is a major challenge
      of the post-genomic era. To date, a systematic approach for describing inter
      species interactions has been lacking. Here we independently predict the
      competitive and cooperative potential between 6,903 bacterial pairs derived from
      a collection of 118 species' metabolic models. We chart an intricate association
      between competition and cooperation indicating that the cooperative potential is
      maximized at moderate levels of resource overlap. Utilizing ecological data from
      2,801 samples, we explore the associations between bacterial interactions and
      coexistence patterns. The high level of competition observed between species with
      mutual-exclusive distribution patterns supports the role of competition in
      community assembly. Cooperative interactions are typically unidirectional with no
      obvious benefit to the giver. However, within their natural communities, bacteria
      typically form close cooperative loops resulting in indirect benefit to all
      species involved. These findings are important for the future design of consortia
      optimized towards bioremediation and bio-production applications.

PMID- 22158445
TI  - -174G/C IL-6 gene promoter polymorphism predicts therapeutic response to TNF
      alpha blockers.
AB  - BACKGROUND: Although TNF-alpha blockade is a very effective therapy for
      psoriasis, not all patients achieve a favorable outcome. The association between
      IL-6 and psoriasis has been investigated but no papers have focused on the
      pharmacogenetics of IL-6. OBJECTIVE: To examine whether the G or the C allele, at
      position -174 in the promoter of IL-6, influences the relationships between body
      weight, body composition, and therapeutic response to TNF-alpha blockers in
      psoriasis. METHODS: Sixty patients with psoriasis were studied, at baseline and 6
      month follow-up after therapy. Assessment of the -174G/C IL-6 polymorphism,
      Psoriasis Area and Severity Index and Disease Activity Score-28 scores, body
      weight (kg), BMI, body composition by Dual-energy X-ray absorptiometry, and
      systemic inflammation was performed. RESULTS: Relevant body composition changes
      occurred after therapy. Normal weight participants showed a greater increase in
      fat mass than lean mass, compared with obese participants. According to their
      genotypes, C(+) carriers showed a greater increase in lean mass and fat mass, at
      the abdominal region, with respect to C(-) carriers. C(+) carriers outweighed C(
      ) carriers in the group of treatment responders. A higher number of responders
      were present among normal weight participants, with respect to obese
      participants. Obesity and the -174G/C IL-6 polymorphism predicted poor response
      to TNF-alpha blockers [odds ratio for C(-) carriers, obese: 2.00 (confidence
      interval: 1.19-3.38; P<=0.05)]. CONCLUSION: Our data show that the G allele of
      the -174G/C IL-6 polymorphism and obesity can be considered as risk factors for
      the prognosis and management of psoriasis. This is the first study to suggest the
      -174G/C IL-6 polymorphism as a novel genetic marker of responsiveness to TNF
      alpha blockers in psoriasis.

PMID- 22158446
TI  - Association of the GGCX (CAA)16/17 repeat polymorphism with higher warfarin dose
      requirements in African Americans.
AB  - OBJECTIVE: Little is known about genetic contributors to higher than usual
      warfarin dose requirements, particularly for African Americans. This study tested
      the hypothesis that the gamma-glutamyl carboxylase (GGCX) genotype contributes to
      warfarin dose requirements greater than 7.5 mg/day in an African American
      population. METHODS: A total of 338 African Americans on a stable dose of
      warfarin were enrolled. The GGCX rs10654848 (CAA)n, rs12714145 (G>A), and
      rs699664 (p.R325Q); VKORC1 c.-1639G>A and rs61162043; and CYP2C9*2, *3, *5, *8,
      *11, and rs7089580 genotypes were tested for their association with dose
      requirements greater than 7.5 mg/day alone and in the context of other variables
      known to influence dose variability. RESULTS: The GGCX rs10654848 (CAA)16 or 17
      repeat occurred at a frequency of 2.6% in African Americans and was
      overrepresented among patients requiring greater than 7.5 mg/day versus those who
      required lower doses (12 vs. 3%, P=0.003; odds ratio 4.0, 95% confidence
      interval, 1.5-10.5). The GGCX rs10654848 genotype remained associated with high
      dose requirements on regression analysis including age, body size, and VKORC1
      genotype. On linear regression, the GGCX rs10654848 genotype explained 2% of the
      overall variability in warfarin dose in African Americans. An examination of the
      GGCX rs10654848 genotype in warfarin-treated Caucasians revealed a (CAA)16 repeat
      frequency of only 0.27% (P=0.008 compared with African Americans). CONCLUSION:
      These data support the GGCX rs10654848 genotype as a predictor of higher than
      usual warfarin doses in African Americans, who have a 10-fold higher frequency of
      the (CAA)16/17 repeat compared with Caucasians.

PMID- 22158447
TI  - [Europe against Babel: an Almanac from the Editors' Network of the European
      Society of Cardiology].

PMID- 22158448
TI  - [The Symplicity HTN-2 study].

PMID- 22158449
TI  - [Almanac 2011: heart failure. An editorial overview of selected research that has
      driven recent advances in clinical cardiology].

PMID- 22158450
TI  - [Metformin and insulin in chronic heart failure: contraindications not
      contraindicated and indications not indicated].
AB  - Glucose-lowering treatment in patients with type 2 diabetes and heart failure is
      controversial. Metformin is clearly contraindicated when such diseases coexist.
      Conversely, no contraindications have been established for insulin in this subset
      of patients, even though several observational and retrospective studies have
      shown increased mortality and worsening heart failure. Data from the literature
      have demonstrated that in this patient population, which accounts for one third
      of all cases of heart failure, metformin reduces mortality by 14-35%. In patients
      with a glomerular filtration rate >30 ml/min who do not show dehydration, shock,
      sepsis, severe liver disease or hypoxemia, the administration of metformin doses
      <2 g/day was associated with a null risk of lactic acidosis. The positive effects
      of metformin are correlated with the reduction in insulin resistance, which is
      responsible for both the onset and development of heart failure in diabetic
      patients. Insulin can provoke severe hypoglycemia and fluid retention, resulting
      in negative effects. Further randomized and prospective studies are warranted to
      address these controversial issues in such a large population with high mortality
      and morbidity rates. Longitudinal studies would be crucial to the understanding
      of the optimal therapy and for stratification of patients according to the
      severity of heart failure.

PMID- 22158451
TI  - [Myocardial dysfunction during sepsis: epidemiology, prognosis and treatment].
AB  - About 50% of patients with sepsis show myocardial involvement characterized by
      biventricular enlargement, reduced contractility and diastolic dysfunction. This
      increases the risk of death and leads to an extremely poor prognosis in the case
      of severe sepsis or septic shock, with full recovery of cardiac function seen in
      survivors at 7-10 days. The pathogenesis of myocardial dysfunction has long been
      investigated and, although it is still not fully understood, seems not to be due
      to reduced coronary flow, but to circulating substances released by pathogens
      (e.g. endotoxins) and host immuno-inflammatory responses (e.g. cytokines and
      mechanisms related to nitric oxide). First-line therapy is causal and consists of
      antibiotics plus the surgical excision of the infectious focus; in the presence
      of severe sepsis or septic shock, it is also necessary to promptly start
      circulatory and multiorgan support treatment. This review describes current
      knowledge concerning the instrumental and clinical characteristics,
      pathophysiology, prognosis and therapy of myocardial dysfunction during sepsis,
      and briefly considers possible future therapeutic perspectives.

PMID- 22158452
TI  - [Disease progression and systolic dysfunction in patients with hypertrophic
      cardiomyopathy: genetic basis, pathophysiology and clinical presentation].
AB  - Progressive heart failure associated with left ventricular remodeling and systo
      diastolic dysfunction is one of the most severe complications of hypertrophic
      cardiomyopathy (HCM). Such condition, for the lack of a better term, is referred
      to as end-stage (ES) HCM. During the last decade, we have begun to understand the
      mechanisms underlying progression from a hyperdynamic left ventricle to the
      striking patterns of ES. To date, different aspects of HCM progression remain
      obscure, including potential strategies for management and prevention. On the
      basis of recent evidence, it is appropriate to emphasize these aspects, which may
      be difficult to identify, particularly in the early stages when systolic function
      appears relatively preserved. Nevertheless, it is at these early stages that
      treatment may potentially interfere with the clinical evolution of HCM toward ES
      and heart failure. The possibility of early identification of patients at risk of
      ES progression may ultimately impact on the natural history of the disease in
      this challenging patient subgroup.

PMID- 22158453
TI  - [Nitrates at high altitude, that is the inappropriate use of a drug].

PMID- 22158454
TI  - [Home-based telemonitoring of simple vital signs to reduce hospitalization in
      heart failure patients: real-world data from a community-based hospital].
AB  - BACKGROUND: Whether home telemonitoring after acute episodes of heart failure
      (HF) may reduce de-novo cardiac decompensation is disputed. We tested home
      telemonitoring of blood pressure (BP), heart rate (HR), and blood oxygen
      saturation (SO2) to reduce rehospitalization in patients with recent admission
      for acute HF. METHODS; We screened patients hospitalized in Cardiology due to
      prominent cardiac cause of acute dyspnea, and pulmonary/peripheral congestion,
      and with one admission or more for similar symptoms/signs in the previous year.
      Patients with acute coronary syndrome, poor prognosis due to extracardiac causes,
      and reduced self-sufficiency and cognitive ability were excluded. Of the selected
      patients, 63% accepted and received a device for BP, HR and SO2 measurement
      connected to an analogical modem for data transmission to a hospital server.
      Patients were educated to measure vital signs 3 times/week. A dedicated doctor
      nurse unit monitored the patients' data twice weekly to manage therapeutic
      adjustments of diuretic dosage or in-hospital visits if necessary. HF treatment
      was standardized based on current guidelines. Unplanned hospitalizations for HF
      or all-cause death were primary endpoints; unplanned hospitalizations (total) for
      any cause, and all-cause death were the composite endpoints. RESULTS: Twenty
      three patients (mean age 70 years, range 44-80 years) were recruited: 26% were
      women, 61% had coronary heart disease, 52% chronic lung disease, 57% renal
      insufficiency, 30% anemia; 17% had moderate or severe mitral regurgitation. At a
      mean follow-up of 302 days (range 55-622 days), 12 patients experienced the
      composite endpoints (52%, p=0.1), with the primary endpoint occurring in 8
      patients (35%, 1 sudden death, p=0.058), the secondary endpoints occurring in 2
      patients, and hospitalization not for HF occurring in 2 patients. The total
      number of hospitalizations/patient/year decreased from 2.2 +/- 1.3 in the
      previous year to 0.9 +/- 1.2 during the study period (p<0.01). On average,
      systolic BP tended to decrease, but BP, HR and SO 2 values prior to the index
      event (1-7 days) did not significantly differ from those recorded at the
      beginning of telemonitoring. CONCLUSIONS: In HF, home telemonitoring of simple
      variables had no significant impact on all-cause hospitalization/mortality, but
      was associated with a higher patient compliance and achievement of therapeutic
      targets, which may translate into a reduction in hospitalization rates for HF.

PMID- 22158455
TI  - [Use of remote telemonitoring in chronic heart failure].

PMID- 22158456
TI  - [Left ventricular assist device recipients at risk of right ventricular failure:
      the role of a planned temporary biventricular support].
AB  - BACKGROUND: When patients at high risk for failure of isolated left ventricular
      assist device (LVAD) support are identified, biventricular assist device
      implantation is suggested as a primary option. Results of a planned temporary
      right ventricular mechanical support (RVAD) placement in high-risk LVAD
      recipients have been reported and analyzed. METHODS: Between 2009 and 2011, 10
      consecutive adult patients (9 men; age range 31-69 years), with preoperative
      evidence of moderate to severe biventricular failure, were supported
      simultaneously with an axial flow HeartMate II (Thoratec Corp., Pleasanton,
      California) LVAD and a temporary CentriMag (Levitronix LCC, Waltham,
      Massachusetts) RVAD as a primary option at our institution. Indications for
      support at implantation were ischemic dilated cardiomyopathy in 6 cases and
      idiopathic dilated cardiomyopathy in 4. Planned temporary RVAD insertion was
      defined as RVAD support placement at the same time as LVAD placement. RESULTS:
      Nine patients were successfully weaned from temporary RVAD support after an
      average time of 18.6 days (range 3-43 days) and discharged from hospital. One
      patient died due to respiratory failure. RVAD removal was performed through a
      minimally invasive approach without repeat sternotomy in 6 patients. None of the
      patients required a permanent RVAD support. CONCLUSIONS: When patients at high
      risk for failure of isolated LVAD support are identified, temporary biventricular
      assist device implantation is advised to improve the outcome of such a vulnerable
      patient population.

PMID- 22158457
TI  - [Does cardiac magnetic resonance imaging complement or replace endomyocardial
      biopsy in the diagnosis of myocarditis? In the era of cardiac magnetic resonance
      imaging, indications for endomyocardial biopsy are limited].

PMID- 22158458
TI  - [Does cardiac magnetic resonance imaging complement or replace endomyocardial
      biopsy in the diagnosis of myocarditis? Endomyocardial biopsy is irreplaceable].

PMID- 22158459
TI  - [Large atrial myxoma: an unexpected clinical presentation].

PMID- 22158460
TI  - Thematic analysis of readmission into inpatient units for adults with
      intellectual disabilities: two case studies.
AB  - This audit explores readmissions into inpatient services for adults with
      intellectual disabilities, using two case studies. Thirteen semi-structured
      interviews were conducted with professionals, to gain a multidisciplinary
      perspective, between February and March 2010, and analysed using thematic
      analysis. The main themes found in case study 1 were: narrow focus, environment,
      communication, early discharge, and deterioration. The main themes found in case
      study 2 were: deterioration, communication, discharge too soon, and environment.
      The aims of the audit were to contribute to good practice and provide a better
      understanding of readmission within our services.

PMID- 22158461
TI  - Disability impact and coping in mothers of children with intellectual
      disabilities and multiple disabilities.
AB  - Understanding the disability impact on parenting and caregiving is important for
      intervention. The present study was designed to understand the differences in
      perceived disability impact and related coping in mothers having children with
      intellectual disabilities alone compared to those having children with
      intellectual disabilities and additional disabilities. Accordingly, 30 mothers of
      children with intellectual disabilities and 30 mothers of children with
      intellectual and additional disabilities were assessed for disability impact and
      coping. Group differences for disability impact were present in specific domains
      but not overall. Despite variations in coping pattern, both positive and negative
      coping strategies were observed in both groups. The results may imply that the
      impact of intellectual disability is so pervasive that except in certain domains
      mothers may not perceive the further impact of additional disabilities. Positive
      coping does not rule out negative coping strategies. These findings have specific
      relevance to service delivery in a cultural context.

PMID- 22158462
TI  - Multifocal electroretinograms.
AB  - A limitation of traditional full-field electroretinograms (ERG) for the diagnosis
      of retinopathy is lack of sensitivity. Generally, ERG results are normal unless
      more than approximately 20% of the retina is affected. In practical terms, a
      patient might be legally blind as a result of macular degeneration or other
      scotomas and still appear normal, according to traditional full field ERG. An
      important development in ERGs is the multifocal ERG (mfERG). Erich Sutter adapted
      the mathematical sequences called binary m-sequences enabling the isolation from
      a single electrical signal an electroretinogram representing less than each
      square millimeter of retina in response to a visual stimulus. Results that are
      generated by mfERG appear similar to those generated by flash ERG. In contrast to
      flash ERG, which best generates data appropriate for whole-eye disorders. The
      basic mfERG result is based on the calculated mathematical average of an
      approximation of the positive deflection component of traditional ERG response,
      known as the b-wave. Multifocal ERG programs measure electrical activity from
      more than a hundred retinal areas per eye, in a few minutes. The enhanced spatial
      resolution enables scotomas and retinal dysfunction to be mapped and quantified.
      In the protocol below, we describe the recording of mfERGs using a bipolar
      speculum contact lens. Components of mfERG systems vary between manufacturers.
      For the presentation of visible stimulus, some suitable CRT monitors are
      available but most systems have adopted the use of flat-panel liquid crystal
      displays (LCD). The visual stimuli depicted here, were produced by a LCD
      microdisplay subtending 35-40 degrees horizontally and 30-35 degrees vertically
      of visual field, and calibrated to produce multifocal flash intensities of 2.7 cd
      s m(-2). Amplification was 50K. Lower and upper bandpass limits were 10 and 300
      Hz. The software packages used were VERIS versions 5 and 6.

PMID- 22158463
TI  - Asymmetric dimethylarginine, arginine and homoarginine at 11-13 weeks' gestation
      and preeclampsia: a case-control study.
AB  - The aim of this study was to investigate whether the nitric oxide (NO) pathway is
      altered in pregnancies that develop preeclampsia (PE). This was a nested case
      control study of screening for PE, in which plasma asymmetric dimethylarginine
      (ADMA), L-arginine and L-homoarginine were measured at 11(+0)-13(+6) weeks. In
      all, 75 pregnancies that developed PE, including 25 requiring delivery before 34
      weeks (early PE), and 300 unaffected controls were included. L-arginine and L
      homoarginine were measured by gas chromatography-mass spectrometry, whereas ADMA
      was measured by gas chromatography-tandem mass spectrometry. Multiple regression
      analysis was used to determine if any maternal characteristics or gestation were
      significant predictors. In the early-PE group, both L-arginine and L-homoarginine
      expected medians (MoMs) were significantly reduced (median, IQR: 0.85, 0.76-1.04
      vs 0.98, 0.88-1.16, P=0.021 and 0.78, 0.65-0.96 vs 0.99, 0.77-1.31, P=0.006,
      respectively) but ADMA MoMs were not significantly different (P=0.599). In early
      PE, compared with controls, the ratios of ADMA to L-arginine MoMs and ADMA to L
      homoarginine MoMs were increased (median, IQR: 1.19, 0.94-1.33 vs 1.01, 0.75
      1.31, P=0.003 and 1.21, 0.93-1.61 vs 0.99, 0.87-1.16, P=0.012, respectively).
      There were no significant differences between late PE and controls in ADMA, L
      arginine, L-homoarginine or their ratios. In conclusion, development of early PE
      is associated with altered NO metabolism and/or synthesis apparent from the first
      trimester.

PMID- 22158464
TI  - POPCORN functions in the auxin pathway to regulate embryonic body plan and
      meristem organization in Arabidopsis.
AB  - The shoot and root apical meristems (SAM and RAM) formed during embryogenesis are
      crucial for postembryonic plant development. We report the identification of
      POPCORN (PCN), a gene required for embryo development and meristem organization
      in Arabidopsis thaliana. Map-based cloning revealed that PCN encodes a WD-40
      protein expressed both during embryo development and postembryonically in the SAM
      and RAM. The two pcn alleles identified in this study are temperature sensitive,
      showing defective embryo development when grown at 22 degrees C that is rescued
      when grown at 29 degrees C. In pcn mutants, meristem-specific expression of
      WUSCHEL (WUS), CLAVATA3, and WUSCHEL-RELATED HOMEOBOX5 is not maintained;
      SHOOTMERISTEMLESS, BODENLOS (BDL) and MONOPTEROS (MP) are misexpressed. Several
      findings link PCN to auxin signaling and meristem function: ectopic expression of
      DR5(rev):green fluorescent protein (GFP), pBDL:BDL-GFP, and pMP:MP-beta
      glucuronidase in the meristem; altered polarity and expression of pPIN1:PIN1-GFP
      in the apical domain of the developing embryo; and resistance to auxin in the pcn
      mutants. The bdl mutation rescued embryo lethality of pcn, suggesting that
      improper auxin response is involved in pcn defects. Furthermore, WUS, PINFORMED1,
      PINOID, and TOPLESS are dosage sensitive in pcn, suggesting functional
      interaction. Together, our results suggest that PCN functions in the auxin
      pathway, integrating auxin signaling in the organization and maintenance of the
      SAM and RAM.

PMID- 22158465
TI  - Syringyl lignin is unaltered by severe sinapyl alcohol dehydrogenase suppression
      in tobacco.
AB  - The manipulation of lignin could, in principle, facilitate efficient biofuel
      production from plant biomass. Despite intensive study of the lignin pathway,
      uncertainty exists about the enzyme catalyzing the last step in syringyl (S)
      monolignol biosynthesis, the reduction of sinapaldehyde to sinapyl alcohol.
      Traditional schemes of the pathway suggested that both guaiacyl (G) and S
      monolignols are produced by a single substrate-versatile enzyme, cinnamyl alcohol
      dehydrogenase (CAD). This was challenged by the discovery of a novel sinapyl
      alcohol dehydrogenase (SAD) that preferentially uses sinapaldehyde as a substrate
      and that was claimed to regulate S lignin biosynthesis in angiosperms.
      Consequently, most pathway schemes now show SAD (or SAD and CAD) at the
      sinapaldehyde reduction step, although functional evidence is lacking. We cloned
      SAD from tobacco (Nicotiana tabacum) and suppressed it in transgenic plants using
      RNA interference-inducing vectors. Characterization of lignin in the woody stems
      shows no change to content, composition, or structure, and S lignin is normal. By
      contrast, plants additionally suppressed in CAD have changes to lignin structure
      and S:G ratio and have increased sinapaldehyde in lignin, similar to plants
      suppressed in CAD alone. These data demonstrate that CAD, not SAD, is the enzyme
      responsible for S lignin biosynthesis in woody angiosperm xylem.

PMID- 22158466
TI  - The RPT2 subunit of the 26S proteasome directs complex assembly, histone
      dynamics, and gametophyte and sporophyte development in Arabidopsis.
AB  - The regulatory particle (RP) of the 26S proteasome contains a heterohexameric
      ring of AAA-ATPases (RPT1-6) that unfolds and inserts substrates into the core
      protease (CP) for degradation. Through genetic analysis of the Arabidopsis
      thaliana gene pair encoding RPT2, we show that this subunit plays a critical role
      in 26S proteasome assembly, histone dynamics, and plant development. rpt2a rpt2b
      double null mutants are blocked in both male and female gamete transmission,
      demonstrating that the subunit is essential. Whereas rpt2b mutants are
      phenotypically normal, rpt2a mutants display a range of defects, including
      impaired leaf, root, trichome, and pollen development, delayed flowering, stem
      fasciation, hypersensitivity to mitomycin C and amino acid analogs,
      hyposensitivity to the proteasome inhibitor MG132, and decreased 26S complex
      stability. The rpt2a phenotype can be rescued by both RPT2a and RPT2b, indicative
      of functional redundancy, but not by RPT2a mutants altered in ATP
      binding/hydrolysis or missing the C-terminal hydrophobic sequence that docks the
      RPT ring onto the CP. Many rpt2a phenotypes are shared with mutants lacking the
      chromatin assembly factor complex CAF1. Like caf1 mutants, plants missing RPT2a
      or reduced in other RP subunits contain less histones, thus implicating RPT2
      specifically, and the 26S proteasome generally, in plant nucleosome assembly.

PMID- 22158467
TI  - Massive analysis of rice small RNAs: mechanistic implications of regulated
      microRNAs and variants for differential target RNA cleavage.
AB  - Small RNAs have a variety of important roles in plant development, stress
      responses, and other processes. They exert their influence by guiding mRNA
      cleavage, translational repression, and chromatin modification. To identify
      previously unknown rice (Oryza sativa) microRNAs (miRNAs) and those regulated by
      environmental stress, 62 small RNA libraries were constructed from rice plants
      and used for deep sequencing with Illumina technology. The libraries represent
      several tissues from control plants and plants subjected to different
      environmental stress treatments. More than 94 million genome-matched reads were
      obtained, resulting in more than 16 million distinct small RNA sequences. This
      allowed an evaluation of ~400 annotated miRNAs with current criteria and the
      finding that among these, ~150 had small interfering RNA-like characteristics.
      Seventy-six new miRNAs were found, and miRNAs regulated in response to water
      stress, nutrient stress, or temperature stress were identified. Among the new
      examples of miRNA regulation were members of the same miRNA family that were
      differentially regulated in different organs and had distinct sequences Some of
      these distinct family members result in differential target cleavage and provide
      new insight about how an agriculturally important rice phenotype could be
      regulated in the panicle. This high-resolution analysis of rice miRNAs should be
      relevant to plant miRNAs in general, particularly in the Poaceae.

PMID- 22158468
TI  - Arabidopsis ATM and ATR kinases prevent propagation of genome damage caused by
      telomere dysfunction.
AB  - The ends of linear eukaryotic chromosomes are hidden in nucleoprotein structures
      called telomeres, and loss of the telomere structure causes inappropriate repair,
      leading to severe karyotypic and genomic instability. Although it has been shown
      that DNA damaging agents activate a DNA damage response (DDR), little is known
      about the signaling of dysfunctional plant telomeres. We show that absence of
      telomerase in Arabidopsis thaliana elicits an ATAXIA-TELANGIECTASIA MUTATED (ATM)
      and ATM AND RAD3-RELATED (ATR)-dependent DDR at telomeres, principally through
      ATM. By contrast, telomere dysfunction induces an ATR-dependent response in
      telomeric Conserved telomere maintenance component1 (Ctc1)-Suppressor of cdc
      thirteen (Stn1)-Telomeric pathways in association with Stn1 (CST)-complex
      mutants. These results uncover a new role for the CST complex in repressing the
      ATR-dependent DDR pathway in plant cells and show that plant cells use two
      different DNA damage surveillance pathways to signal telomere dysfunction. The
      absence of either ATM or ATR in ctc1 and stn1 mutants significantly enhances
      developmental and genome instability while reducing stem cell death. These data
      thus give a clear illustration of the action of ATM/ATR-dependent programmed cell
      death in maintaining genomic integrity through elimination of genetically
      unstable cells.

PMID- 22158469
TI  - Progression of monoclonal gammopathy of undetermined significance to multiple
      myeloma in a solid organ transplant.

PMID- 22158471
TI  - Concomitant Epstein-Barr virus (EBV)-positive B-cell and EBV-negative T-cell
      posttransplant lymphoproliferative disorders after renal allografting:
      pathogenetic implications.

PMID- 22158472
TI  - An interleukin-2-IgG-Fas ligand fusion protein suppresses delayed-type
      hypersensitivity in mice by triggering apoptosis in activated T cells as a novel
      strategy for immunosuppression. Retraction.

PMID- 22158473
TI  - Polycystic kidney disease in 2011: Connecting the dots toward a polycystic kidney
      disease therapy.
AB  - Understanding the complex interactions between the various pathways disrupted in
      polycystic kidney and liver disease is essential to identify and optimize
      therapies for these disorders. Studies published in the past year have
      demonstrated a functional interaction between the main proteins implicated in
      these diseases and identified novel therapeutic approaches.

PMID- 22158474
TI  - Dialysis in 2011: Can cardiovascular risk in dialysis patients be decreased?
AB  - More than 1.4 million patients are on renal replacement therapy worldwide.
      Mortality in patients with end-stage renal disease (ESRD) is as high as that seen
      in some types of metastatic cancer, and premature cardiovascular disease is the
      major killer in ESRD. Several publications in 2011 addressed how interventions
      can modify cardiovascular risk factors and improve outcomes.

PMID- 22158475
TI  - Glomerular disease in 2011: New clues to environmental influences in glomerular
      disease.
AB  - Research into genetic susceptibilities for proteinuric glomerular diseases has
      uncovered key pathogenic contributions from inheritable defects in podocytes.
      However, much less is known about environmental factors that may initiate or
      propagate podocyte injury. Seminal reports in 2011 provided new mechanistic
      insights into how this may occur.

PMID- 22158477
TI  - Neuroprotection by leptin in a rat model of permanent cerebral ischemia: effects
      on STAT3 phosphorylation in discrete cells of the brain.
AB  - In addition to its effects in the hypothalamus to control body weight, leptin is
      involved in the regulation of neuronal function, development and survival. Recent
      findings have highlighted the neuroprotective effects of leptin against ischemic
      brain injury; however, to date, little is known about the role performed by the
      signal transducer and activator of transcription (STAT)-3, a major mediator of
      leptin receptor transduction pathway in the brain, in the beneficial effects of
      the hormone. Our data demonstrate that systemic acute administration of leptin
      produces neuroprotection in rats subjected to permanent middle cerebral artery
      occlusion (MCAo), as revealed by a significant reduction of the brain infarct
      volume and neurological deficit up to 7 days after the induction of ischemia. By
      combining a subcellular fractionation approach with immunohistofluorescence, we
      observe that neuroprotection is associated with a cell type-specific modulation
      of STAT3 phosphorylation in the ischemic cortex. The early enhancement of nuclear
      phospho-STAT3 induced by leptin in the astrocytes of the ischemic penumbra may
      contribute to a beneficial effect of these cells on the evolution of tissue
      damage. In addition, the elevation of phospho-STAT3 induced by leptin in the
      neurons after 24 h MCAo is associated with an increased expression of tissue
      inhibitor of matrix metalloproteinases-1 in the cortex, suggesting its possible
      involvement to the neuroprotection produced by the adipokine.

PMID- 22158476
TI  - Cyclic AMP induces IPC leukemia cell apoptosis via CRE-and CDK-dependent Bim
      transcription.
AB  - The IPC-81 cell line is derived from the transplantable BNML model of acute
      myelogenic leukemia (AML), known to be a reliable predictor of the clinical
      efficiency of antileukemic agents, like the first-line AML anthracycline drug
      daunorubicin (DNR). We show here that cAMP acted synergistically with DNR to
      induce IPC cell death. The DNR-induced death differed from that induced by cAMP
      by (1) not involving Bim induction, (2) being abrogated by GSK3beta inhibitors,
      (3) by being promoted by the HSP90/p23 antagonist geldanamycin and truncated p23
      and (4) by being insensitive to the CRE binding protein (CREB) antagonist ICER
      and to cyclin-dependent protein kinase (CDK) inhibitors. In contrast, the
      apoptosis induced by cAMP correlated tightly with Bim protein expression. It was
      abrogated by Bim (BCL2L11) downregulation, whether achieved by the CREB
      antagonist ICER, by CDK inhibitors, by Bim-directed RNAi, or by protein synthesis
      inhibitor. The forced expression of BimL killed IPC-81(WT) cells rapidly, Bcl2
      overexpressing cells being partially resistant. The pivotal role of CREB and CDK
      activity for Bim transcription is unprecedented. It is also noteworthy that newly
      developed cAMP analogs specifically activating PKA isozyme I (PKA-I) were able to
      induce IPC cell apoptosis. Our findings support the notion that AML cells may
      possess targetable death pathways not exploited by common anti-cancer agents.

PMID- 22158478
TI  - Non-coding rRNA-mediated preferential killing in cancer cells is enhanced by
      suppression of autophagy in non-transformed counterpart.
AB  - Interest to anticancer agents targeting rRNA biogenesis is growing. Cis-non
      coding rRNAs, alternative to primary rRNA, have been shown to regulate rRNA
      biogenesis. We have recently detected bidirectional non-coding rRNAs that carry
      ribozyme-like properties. Anti-antisense oligonucleotides complementary to
      antisense non-coding rRNAs markedly stabilized the bidirectional transcripts and
      induced cell death in mouse lung cells. Here, we demonstrated that the same
      oligonucleotide killed mouse lung-cancer cells preferentially, compared with non
      cancer sister lines, suggesting its potential utility for cancer treatment. A
      human version of anti-antisense oligonucleotide, complementary to an rDNA
      intergenic site, mediated apoptosis primarily in cancer cells. Autophagic
      activation was largely undifferentiable between the anti-antisense and other
      oligonucleotides and accounted for the undesired cytotoxicity in non-cancer
      cells. Co-treatment with chloroquine, an autophagy inhibitor, reduced
      cytotoxicity in the non-cancer cells, but retained the anti-antisense-mediated
      killings in cancer cells. Furthermore, the anti-antisense oligonucleotide
      stabilized bidirectional non-coding rRNAs predominantly in human cancer cells and
      perturbed rRNA biogenesis. Contributions of non-coding rRNAs to cell death were
      proven by transfection of in -vitro-synthesized transcripts. Taken together,
      cancer/non-cancer cells respond differently to stabilization of non-coding rRNAs,
      and such differential responses provide a window of opportunity to enhance
      anticancer efficacy.

PMID- 22158480
TI  - Serine/threonine protein phosphatase 6 modulates the radiation sensitivity of
      glioblastoma.
AB  - Increasing the sensitivity of glioblastoma cells to radiation is a promising
      approach to improve survival in patients with glioblastoma multiforme (GBM). This
      study aims to determine if serine/threonine phosphatase (protein phosphatase 6
      (PP6)) is a molecular target for GBM radiosensitization treatment. The GBM
      orthotopic xenograft mice model was used in this study. Our data demonstrated
      that the protein level of PP6 catalytic subunit (PP6c) was upregulated in the GBM
      tissue from about 50% patients compared with the surrounding tissue or control
      tissue. Both the in vitro survival fraction of GBM cells and the patient survival
      time were highly correlated or inversely correlated with PP6c expression
      (R(2)=0.755 and -0.707, respectively). We also found that siRNA knockdown of PP6c
      reduced DNA-dependent protein kinase (DNA-PK) activity in three different GBM
      cell lines, increasing their sensitivity to radiation. In the orthotopic mice
      model, the overexpression of PP6c in GBM U87 cells attenuated the effect of
      radiation treatment, and reduced the survival time of mice compared with the
      control mice, while the PP6c knocking-down improved the effect of radiation
      treatment, and increased the survival time of mice. These findings demonstrate
      that PP6 regulates the sensitivity of GBM cells to radiation, and suggest small
      molecules disrupting or inhibiting PP6 association with DNA-PK is a potential
      radiosensitizer for GBM.

PMID- 22158479
TI  - A new vicious cycle involving glutamate excitotoxicity, oxidative stress and
      mitochondrial dynamics.
AB  - Glutamate excitotoxicity leads to fragmented mitochondria in neurodegenerative
      diseases, mediated by nitric oxide and S-nitrosylation of dynamin-related protein
      1, a mitochondrial outer membrane fission protein. Optic atrophy gene 1 (OPA1) is
      an inner membrane protein important for mitochondrial fusion. Autosomal dominant
      optic atrophy (ADOA), caused by mutations in OPA1, is a neurodegenerative disease
      affecting mainly retinal ganglion cells (RGCs). Here, we showed that OPA1
      deficiency in an ADOA model influences N-methyl-D-aspartate (NMDA) receptor
      expression, which is involved in glutamate excitotoxicity and oxidative stress.
      Opa1(enu/+) mice show a slow progressive loss of RGCs, activation of astroglia
      and microglia, and pronounced mitochondrial fission in optic nerve heads as found
      by electron tomography. Expression of NMDA receptors (NR1, 2A, and 2B) in the
      retina of Opa1(enu/+) mice was significantly increased as determined by western
      blot and immunohistochemistry. Superoxide dismutase 2 (SOD2) expression was
      significantly decreased, the apoptotic pathway was activated as Bax was
      increased, and phosphorylated Bad and BcL-xL were decreased. Our results
      conclusively demonstrate that not only glutamate excitotoxicity and/or oxidative
      stress alters mitochondrial fission/fusion, but that an imbalance in
      mitochondrial fission/fusion in turn leads to NMDA receptor upregulation and
      oxidative stress. Therefore, we propose a new vicious cycle involved in
      neurodegeneration that includes glutamate excitotoxicity, oxidative stress, and
      mitochondrial dynamics.

PMID- 22158481
TI  - What is the best screening strategy to detect advanced colorectal adenomas?
      Simulation from ongoing Italian screening experiences.
AB  - AIMS AND BACKGROUND: The best screening strategy for colorectal cancer is still
      debated. We simulated two screening strategies, namely flexible sigmoidoscopy
      (single episode) and immunological fecal occult blood test (FOBT) (five biennial
      rounds) and comparing their results as regards advanced adenomas and colorectal
      cancer detection. METHODS: A Markov model was developed to estimate the number of
      advanced adenomas and colorectal cancer detected with the two compared screening
      strategies. Two different scenarios, namely a) where the same compliance (50%) at
      both flexible sigmoidoscopy and immunological FOBT invitation is applied, and b)
      where the actual compliance observed at a national level (immunological FOBT,
      45%; flexible sigmoidoscopy, 30%) is applied. RESULTS: In scenario a),
      immunological FOBT would detect a total of 20,573 adenomas and 3,952 colorectal
      cancers, performing 74,507 total colonoscopies compared to 20,939 and 2,511,
      respectively, detected by flexible sigmoidoscopy, with 17,985 total
      colonoscopies. In scenario b), immunological FOBT would detect 17,845 advanced
      adenomas with 65,215 colonoscopies performed compared to 12,672 detected by
      flexible sigmoidoscopy with 10,796 colonoscopies. The probability of having a
      colonoscopy for a subject attending all the five immunological FOBT rounds was
      15.9%. CONCLUSIONS: The simulation suggests that also immunological FOBT
      screening may achieve a substantial detection of advanced adenomas and therefore
      may have an impact on colorectal cancer incidence.

PMID- 22158482
TI  - Variation in gynecological oncology follow-up practice: attributable to cancer
      centers or to patient characteristics? A Piedmont Regional Oncology Network
      Study.
AB  - AIMS AND BACKGROUND: Although guidelines recommend minimalist follow-up, there is
      wide variability in gynecological oncology practice. The aims of this study were
      to describe between-center differences in the follow-up of endometrial, ovarian,
      and uterine cervical cancer; to identify the determinants of test prescription;
      to estimate the related costs; and to assess the weight of center habits and
      patient characteristics as sources of unexplained variability. METHODS AND STUDY
      DESIGN: The medical records of patients treated between August 2004 and July 2005
      for gynecological malignancies and followed up for the detection of recurrent
      disease were retrospectively collected from 29 centers of the Piedmont Oncology
      Network. Multivariate multilevel analyses were performed to study the
      determinants of test prescription and costs. RESULTS: Analyses were performed on
      351 patients (median follow-up: 578 days). The unexplained variability in
      computed tomography prescriptions (26%), ultrasound prescriptions (17%), and
      total cost of follow-up (15%) can be attributed to center habits, independenty of
      the clinical characteristics of the patients. CONCLUSIONS: Much of the
      unexplained variability in the follow-up for gynecological malignancies is
      attributable to different habits of centers belonging to a cancer network. These
      results prompted us to design a multicenter randomized controlled trial to
      compare minimalist versus intensive follow-up programs in endometrial cancer.

PMID- 22158483
TI  - Importance of adherence to guidelines in breast cancer clinical practice. The
      Italian experience (AIOM).
AB  - AIMS AND BACKGROUND: Project RIGHT (Research for the Identification of the most
      effective and hIGHly accepted clinical guidelines for cancer Treatment) is
      promoted by the Italian Association of Medical Oncology (AIOM) to evaluate the
      concordance between AIOM breast cancer guidelines and clinical practice in Italy.
      In RIGHT-1, feasibility and the appropriateness of indicators were assessed in
      patients with early breast cancer. RIGHT-2 evaluated the compliance with
      guidelines in a nationwide program. METHODS: Thirty-five Italian centers
      participated in the RIGHT-2 survey. Ten indicators were evaluated to verify an
      agreement between 2005 AIOM breast cancer guidelines and practice. Patients with
      clinical stage I-II invasive breast cancer, age <=70 years, who had their first
      visit at the oncology center between October 2005 and November 2006 were
      included. RESULTS: In RIGHT-2, >=90% adherence for the diagnosis indicator and
      three therapy indicators were observed. The lowest degree of compliance (0%) was
      observed for the follow-up indicator in asymptomatic patients. CONCLUSIONS: In
      RIGHT-2, compliance to the 2005 AIOM breast cancer guidelines was 64%. When the
      follow-up indicator was eliminated, overall adherence to AIOM guidelines was 71%.
      The results highlight the need to continue improving the already good standards
      of breast cancer care.

PMID- 22158484
TI  - Neuroendocrine tumors of unknown primary site: gold dust or misdiagnosed
      neoplasms?
AB  - AIMS AND BACKGROUND: Neuroendocrine tumors of an unknown primary site are rarer
      than other neuroendocrine tumors (0.6-2% of all neuroendocrine tumors) and have a
      poor prognosis. The aim of the study was to review the cases of unknown primary
      site neuroendocrine tumors encountered at the Istituto Nazionale Tumori of Milan
      between 1984 and 2008 in order to verify their incidence and evaluate their
      characteristics and prognosis. METHODS AND STUDY DESIGN: During the study period,
      750 neuroendocrine tumor patients attended our Institute, 82 of whom (10.9%) were
      diagnosed as having neuroendocrine tumors of an unknown primary site. The data
      from their medical records were analyzed descriptively, and survival
      probabilities were calculated using the Kaplan-Meier method and the logrank test,
      considering patient, tumor and treatment-related characteristics. RESULTS: The 82
      patients with neuroendocrine tumors of an unknown primary site (34 males) had a
      median age of 60 years; 57 (69.5%) had histologically well-differentiated tumors,
      3 (3.7%) poorly differentiated tumors, and 22 (26.8%) had tumors that could not
      be classified. Of the 52 patients (62.2%) who underwent Octreoscan(r) (Bykgulden
      Italia SpA), 40 (78.4%) showed a pathological uptake and 11 (21.6%) were
      negative. Thirty-one patients (37.8%) underwent metastatic site surgery, which
      was radical in 11 cases (35.4%). Forty-eight patients (58.5%) received
      somatostatin analogues, and 41 (50.0%) underwent chemotherapy. At the end of the
      study period, 59 patients (72.0%) had died, 31 (53.0%) because of disease
      progression, and 23 (28.0%) were still alive. CONCLUSIONS: Neuroendocrine tumors
      of an unknown primary site are difficult to identify but their incidence is
      higher than previously reported, and the prognosis remains unfavorable.

PMID- 22158485
TI  - A feasibility study of zoledronic acid combined with carboplatin/nedaplatin plus
      paclitaxel in patients with non-small cell lung cancer with bone metastases.
AB  - AIMS AND BACKGROUND: Although zoledronic acid (ZOL) has been reported to inhibit
      bone metastasis from lung cancer, the optimum chemotherapy regimen in combination
      with ZOL has not yet been determined. METHODS AND STUDY DESIGN: Eighteen patients
      having non-small cell lung cancer (NSCLC) with bone metastasis who received
      carboplatin/nedaplatin plus paclitaxel combined with ZOL (4 mg every 28 days)
      were enrolled to investigate the feasibility of this treatment. The efficacy was
      evaluated by the percentage of patients at 9 months who were receiving radiation
      therapy, the time to first radiation treatment, and quality of life. Adverse
      effects were also evaluated. RESULTS: Only 3 among 18 patients received radiation
      therapy for bone metastases during the 9 months of the study. ZOL seems to
      prolong the median time to the first radiation treatment and maintain the quality
      of life regarding pain and activity status. No patients discontinued the
      treatment, although grade 3 or 4 treatment-related adverse effects occurred in 8
      patients. CONCLUSIONS: ZOL combined with carboplatin/nedaplatin plus paclitaxel
      is an effective and tolerable treatment for NSCLC with bone metastases.

PMID- 22158486
TI  - Reduced use of chemotherapy at the end of life in an integrated-care model of
      oncology and palliative care.
AB  - AIMS AND BACKGROUND: When there is little hope of a clinical benefit, too delayed
      a withdrawal from chemotherapy might be detrimental for a patient's quality of
      life. We evaluated appropriately timed cessation of chemotherapy in our Oncology
      Department after integration of a Supportive and Palliative Care Unit. METHODS:
      We carried out a review of deceased patients in our department from January 2006
      to December 2009. Activities of the Supportive and Palliative Care Unit started
      in late 2007. We analyzed the characteristics of patients near the end of life
      and chemotherapy use within 30 days of death as an aggressiveness of cure index.
      RESULTS: During the considered period, 361 hospitalized patients died: 69 in
      2006, 77 in 2007, 97 in 2008 and 118 in 2009; 102 never received chemotherapy.
      Sixty-one of the remaining 259 patients died within 30 days of the last drug
      administration. The percentage of patients receiving chemotherapy in their last
      30 days fell from 19% in 2006 and 20% in 2007, to 16% in 2008 and 14% in 2009.
      CONCLUSIONS: Supportive and Palliative Care Unit integration decreased
      chemotherapy use in the last 30 days of life. A careful evaluation of prognostic
      factors of advanced cancer patients and provision of appropriate supportive and
      palliative cares can reduce the use of futile anticancer chemotherapy and
      preserve a patient's qualify of life.

PMID- 22158487
TI  - Cytokine serum levels in patients with cervical intraepithelial neoplasia grade
      II-III treated with intralesional interferon-alpha 2b.
AB  - AIMS AND BACKGROUND: Cervical intraepithelial neoplasia (CIN) grade II-III is
      being diagnosed in younger women and, because of the reproductive age range for
      women and the habits associated with a modern lifestyle, is now affecting a broad
      age range. Surgical treatment for CIN has been associated with premature
      amenorrhea, low birth weight, and premature labor and birth. It is therefore
      imperative to develop clinical treatments for CIN, such as conservative treatment
      with interferons. The object of the present study was to evaluate the behavior of
      cytokines (IFN- g, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-alpha, TGF
      beta) in the serum of patients with an initial diagnosis of CIN II-III. METHODS:
      Ten patients with CIN-CIN II (60%, n = 6) and CIN III (40%, n = 4), 23 to 51
      years of age and who had not received any prior treatments, were evaluated. The
      patients were given 3 million/UI (per cm2 of colposcopic lesion) of human
      recombinant IFN-alpha 2b by intralesional administration (18 applications on
      alternate days). Before treatment, in the 6th, 12th, and 18th applications, blood
      was collected from the patients for cytokine analysis using ELISA. RESULTS: Half
      of the patients had a good pathologic response; the other half, all of whom were
      smokers, had therapeutic failure. The average concentration of IL-12 (pg/ml) in
      the serum of patients who responded well to therapy was elevated from the 12th
      and 18th application of IFN-alpha 2b compared to patients who experienced
      therapeutic failure: 1804.0 +/- 1020 vs 391.2 +/- 722.3 and 1738.0 +/- 2426.0 vs
      448.5 +/- 407.2, respectively, P <0.05. CONCLUSIONS: CIN II-III treated with
      intralesional IFN-alpha 2b achieved a good response in non-smoking patients and
      was associated with an increase in IL-12 serum levels.

PMID- 22158489
TI  - Radiation therapy is a treatment to be considered for recurrent epithelial
      ovarian cancer after chemotherapy.
AB  - AIMS AND BACKGROUND: Radiation therapy provides a safe and effective alternative
      treatment option for recurrent epithelial ovarian cancer, although it has not
      been a treatment of choice. We evaluated the efficacy and toxicity of radiation
      therapy for recurrent epithelial ovarian cancer after chemotherapy according to
      the disease status. METHODS: This was a retrospective study of 38 patients with
      recurrent epithelial ovarian cancer treated with radiation therapy at the Asan
      Medical Center, Seoul, Korea, between January 1997 and December 2007. We analyzed
      their clinical characteristics and the outcome of radiation therapy. RESULTS:
      Thirty-eight patients were treated with radiation therapy. Their median age was
      51.5 years. Most patients were FIGO stage III (27/38) with serous adenocarcinoma
      (26/38). All patients had received at least one regimen of platinum-based
      chemotherapy; 24 patients were sensitive to the first chemotherapy and the others
      were resistant. Lymph node and abdominopelvic wall were the most common sites of
      radiation therapy. The response rate was 65.0% (16 complete remissions and 10
      partial remissions), and the median regression rate was 78.8% (range, -66.6 to
      100.0). Median progression-free survival was 7.2 months (range, 1.0-66.6). In 28
      patients who had a solitary relapsed site from the radiographic finding at the
      time of radiation therapy, it was 10.7 months (range, 1.8-66.6). Neither
      hematologic nor intestinal toxicity of grade 3-4 was observed. Prognostic factors
      were sensitivity to platinum and the site treated with radiation therapy.
      CONCLUSIONS: Radiation therapy is a treatment that should be considered for
      recurrent epithelial ovarian cancer, especially in good responders to platinum or
      patients with solitary relapsed lesions.

PMID- 22158488
TI  - Epithelioid angiosarcoma of bone and soft tissue: a report of seven cases with
      emphasis on morphologic diversity, immunohistochemical features and clinical
      outcome.
AB  - AIMS AND BACKGROUND: Epithelioid angiosarcoma is a rare histopathologic variant
      of angiosarcoma characterized by an epithelioid morphology. This subset can
      histologically mimic non-vascular neoplasms and impose serious challenges in
      reaching a correct diagnosis, especially in the context of limited tissue
      sampling (e.g., needle core biopsy). To improve recognition of epithelioid
      angiosarcoma - and the spectrum of morphologic diversity associated with this
      rare variant - and to avoid a misdiagnosis, we describe the clinical,
      histopathologic, and immunohistochemical findings of cases of epithelioid
      angiosarcoma diagnosed at our institution. METHODS AND STUDY DESIGN: Seven cases
      of epithelioid angiosarcoma with appropriate pathologic material were identified
      from our archives. Immunohistochemistry was used to detect the expression of
      CD31, CD34, Factor VIII, cytokeratin, epithelial membrane antigen, vimentin,
      HMB45, CD1a, CD68, lysozyme, CD45, desmin, and smooth muscle actin in all cases.
      Follow-up information was obtained by reviewing medical records or by direct
      communication with family members. RESULTS: The lesions involved the bone (n = 4)
      and soft tissues (n = 3). Microscopically, all tumors had a predominantly diffuse
      growth pattern, with a focal nested architecture in 6 cases, which closely
      mimicked metastatic carcinoma. The initial biopsy was performed in 2 of 6
      patients and revealed the presence of a malignant neoplasm suggestive of
      metastatic carcinoma. Immunohistochemically, the epithelioid endothelial cells
      usually showed strong reactivity for CD31 (7/7), variable or focal positive
      staining for CD34 (5/7), Factor VIII (4/7), cytokeratin (6/7), epithelial
      membrane antigen (2/7), vimentin (7/7), and CD68 (3/7). In contrast, they were
      negative for CD1a, HMB45, lysozyme, CD45, desmin, and smooth muscle actin. Three
      patients died of disease within one year of the diagnosis, 2 patients developed
      local recurrence or metastases, and another 2 were disease-free at this writing.
      CONCLUSIONS: With any unusual epithelioid neoplasm displaying some or all of the
      morphologic features described above, epithelioid angiosarcoma should be included
      in the differential diagnosis. In such an instance, endothelial markers should be
      incorporated in the immunohistochemical analysis to avoid misdiagnosis,
      particularly with limited sampling.

PMID- 22158490
TI  - Dosimetric and clinical predictors of radiation-induced lung toxicity in
      esophageal carcinoma.
AB  - AIMS AND BACKGROUND: Radiation-induced lung toxicity occurs frequently in
      patients with esophageal carcinoma. This study aims to evaluate the clinical and
      three-dimensional dosimetric parameters associated with lung toxicity after
      radiotherapy for esophageal carcinoma. METHODS AND STUDY DESIGN: The records of
      56 patients treated for esophageal carcinoma were reviewed. The Radiation Therapy
      Oncology Group criteria for grading of lung toxicity were followed. Spearman's
      correlation test, the chi-square test and logistic regression analyses were used
      for statistical analysis. RESULTS: Ten of the 56 patients developed acute
      toxicity. The toxicity grades were grade 2 in 7 patients and grade 3 in 3
      patients; none of the patients developed grade 4 or worse toxicity. One case of
      toxicity occurred during radiotherapy and 9 occurred 2 weeks to 3 months after
      radiotherapy. The median time was 2.0 months after radiotherapy. Fourteen
      patients developed late irradiated lung injury, 3 after 3.5 months, 7 after 9
      months, and 4 after 14 months. Radiographic imaging demonstrated patchy
      consolidation (n = 5), atelectasis with parenchymal distortion (n = 6), and solid
      consolidation (n = 3). For acute toxicity, the irradiated esophageal volume,
      number of fields, and most dosimetric parameters were predictive. For late
      toxicity, chemotherapy combined with radiotherapy and other dosimetric parameters
      were predictive. No obvious association between the occurrence of acute and late
      injury was observed. CONCLUSIONS: The percent of lung tissue receiving at least
      25 Gy (V25), the number of fields, and the irradiated length of the esophagus can
      be used as predictors of the risk of acute toxicity. Lungs V30, as well as
      chemotherapy combined with radiotherapy, are predictive of late lung injury.

PMID- 22158491
TI  - Multiphase-computed tomography-based target volume definition in conventional
      fractionated radiotherapy of lung tumors: dosimetric and reliable comparison with
      the technique using addition of generic margins.
AB  - AIMS AND BACKGROUND: The aim of the present study was to compare radiotherapeutic
      plans based on internal target volume determined by between multiphase computed
      tomography and addition of a generic margin in lung tumors and to evaluate the
      reliability of ITV determined by multiphase computed tomography during
      conventional fractionated radiotherapy. METHODS AND STUDY DESIGN: The
      radiotherapeutic plans based on internal target volume determined by between
      multiphase computed tomography and addition of a generic margin in 10 patients
      with lung tumors were applied. The difference of two planning target volumes
      (PTV) and irradiated dose and volume of normal lung tissue were compared. Weekly
      new targets were delineated on repeated computed tomography scans, and weekly
      dose coverage of clinical target volume under two different treatment plans was
      evaluated. RESULTS: For all patients, PTV3CT volume based on multiphase computed
      tomography was significantly smaller than that of PTVcon based on addition of a
      generic margin (t = 6.831, P <0.001). The volume receiving more than 20 Gy in
      Plan3CT and Plancon was 16.7 +/- 5.2% and 20.0 +/- 5.2% (t = 7.565, P <0.001),
      the volume receiving more than 5 Gy was 36.6 +/- 7.2% and 42.7 +/- 6.4% (t =
      7.459, P <0.001), and mean lung dose was 1037.5 +/- 275.0 cGy and 1246.8 +/-
      271.0 cGy (t = 8.078, P <0.001), respectively. Both Plan3CT and Plancon provided
      a satisfactory clinical target volume coverage weekly during conventional
      fractionated radiotherapy for 6-7 weeks, and the ratio of the volume receiving
      the prescription dose was 1.03 +/- 0.02 and 1.04 +/- 0.02, respectively.
      CONCLUSIONS: The radiotherapeutic plan based on internal target volume determined
      by multiphase computed tomography can ensure weekly target coverage during
      conventional fractionated radiotherapy in lung tumors, and it is better than the
      plan based on the addition of generic internal target volume, which can
      effectively reduce normal lung tissue irradiation.

PMID- 22158492
TI  - Defining the role of palliative radiotherapy in bone metastasis from primary
      liver cancer: an analysis of survival and treatment efficacy.
AB  - AIMS AND BACKGROUND: Primary liver cancer is the fourth leading cause of cancer
      related death worldwide and is still associated with a poor prognosis.
      Hepatocellular carcinoma and cholangiocarcinoma are known to cause bone
      metastasis resulting in pain, neurologic impairment and risk of fracture.
      Palliative radiotherapy is the treatment of choice in symptomatic bone lesions
      and is usually performed as percutaneous fractionated radiotherapy. METHODS AND
      STUDY DESIGN: From June 1987 to December 2009, 41 patients (median age, 64 years)
      with bone metastasis received radiotherapy in our department. The analyzed
      patients were treated for 67 sites of bone lesions. We analyzed the applied
      fractionation schedules and the preferred sites of metastasis and symptoms,
      evaluated the therapeutic outcome in terms of symptomatic improvement, and
      described the prognosis of these patients. RESULTS: Main indication for
      palliative radiotherapy was pain in 94% of all cases. Most frequent radiation
      protocols were 10 x 3 Gy (20 patients) and 20 x 2 Gy (19 patients). Median
      applied overall dose was 39 Gy (range, 4-48 Gy) and median single dose was 2.5 Gy
      (range, 1.8-4 Gy). The median duration of the radiotherapeutic treatment was 15
      days (range, 2-24 days) and in 12 cases treatment was discontinuated. The overall
      response rate to palliative radiotherapy in bone metastasis was 77%. Median
      overall survival in both cholangiocarcinoma and hepatocellular carcinoma patients
      was 4.2 months after initiation of radiotherapy (range, 0.2-38.9). CONCLUSIONS:
      Considering the poor prognosis of patients with bone metastasis in hepatocellular
      carcinoma and cholangiocarcinoma, with a poor median survival of 3.7-5.0 months
      according to our study and existing literature, shorter radiotherapy schedules or
      even single-fraction irradiation can be considered.

PMID- 22158493
TI  - Treatment of recurrent high-grade gliomas  with GliaSite brachytherapy: a
      prospective mono-institutional Italian experience.
AB  - AIMS AND BACKGROUND: The present study evaluated toxicity, local control, and
      survival in patients with relapsed high-grade glioma after surgery and external
      beam radiation therapy and treated with re-operation and GliaSite brachytherapy.
      METHODS: Between 2006 and 2008, 15 patients with recurrent high-grade glioma
      underwent re-operation and GliaSite brachytherapy. Ten patients were males and 5
      females. Median age was 40 years (range, 20-71). Karnofsky performance status was
      >=70. All patients but one received GliaSite irradiation of the surgical cavity
      wall at the dose of 4500 cGy at a depth of 1 cm. RESULTS: No severe acute side
      effects were observed during GliaSite brachytherapy. Pathologically documented,
      symptomatic late radiation necrosis was observed in 3 patients (20%); 2
      subsequently died of further complications. Two patients were alive at a median
      follow-up 13 months (range, 1-30). Median overall survival after GliaSite
      brachytherapy was 13 months. CONCLUSIONS: Patients with recurrent high-grade
      glioma can be treated with additional surgery and GliaSite brachytherapy,
      delivering 4500 cGy at 1 cm depth without significant acute side effects but with
      a significant rate (20%) of late radiation necrosis, resulting in 13% of
      treatment-related deaths. Compared with the literature, survival results in our
      study appear to be satisfactory, but they may be related to patient selection
      criteria. Re-intervention followed by GliaSite brachytherapy should not be
      offered as a standard treatment for recurrent high-grade glioma, because of the
      high rate of late complications, treatment-related deaths, and high treatment
      costs.

PMID- 22158494
TI  - Detection of somatostatin receptor subtypes 2 and 5 by somatostatin receptor
      scintigraphy and immunohistochemistry: clinical implications in the diagnostic
      and therapeutic management of gastroenteropancreatic neuroendocrine tumors.
AB  - AIMS AND BACKGROUND: Somatostatin receptor scintigraphy (SRS) is the standard
      method for the detection of somatostatin receptors (SSTRs). It is commonly used
      in gastroenteropancreatic neuroendocrine tumor (GEP-NET) staging, and represents
      the criterion of choice for treatment with somatostatin (SST) analogs.
      Immunohistochemistry (IHC) was reported as a reliable method for the detection of
      SSTRs with theoretically superior sensitivity over SRS. METHODS AND STUDY DESIGN:
      We retrospectively analyzed the sensitivity and specificity of IHC in the
      detection of SSTRs in a cohort of consecutive patients with GEP-NETs attending
      our Institute from 1997 to 2007. IHC analysis was restricted to SSTR2 and SSTR5,
      and the results were interpreted according to two different scoring systems. SRS
      was used as the gold standard. Results. Forty-four patients were enrolled; 24
      (55%) had foregut carcinoids, 9 (20%) midgut carcinoids, 2 (5%) hindgut
      carcinoids, and 9 (20%) had GEP-NETs of unknown primary sites. A high concordance
      rate between IHC and SRS was shown, irrespective of the IHC scoring system
      applied (73% and 70%). The sensitivity of IHC was 89.3% and 78.6% and the
      specificity 43.8% and 50%, depending on the scoring system used. CONCLUSIONS:
      Although SSTR2 was shown to be expressed by IHC in up to 50% of tumors not
      visualized by SRS, SRS still remains the method of choice in the diagnostic and
      therapeutic management of GEP-NETs. More pathological and clinical data are
      needed to properly understand the clinical relevance of immunohistochemical
      detection of SSTR expression in the absence of tumor uptake at SRS.

PMID- 22158495
TI  - Multi-field-of-view SPECT is superior  to whole-body scanning for assessing
      metastatic bone disease in patients with prostate cancer.
AB  - AIM: The aim of this study was to compare the diagnostic performance of whole
      body bone scintigraphy (WBS) and multi-field-of-view single photon emission
      tomography (multi-FOV SPECT) with 99mTc-oxidronate (99mTc-HDP) in patients with
      prostate cancer (PCa). METHODS: In a prospective study, WBS and SPECT
      acquisitions were performed in 194 patients with histologically confirmed PCa and
      serum prostate-specific antigen (PSA) levels above 10 ng/mL. Scans obtained using
      the two modalities were interpreted separately. Clinical and biochemical follow
      up, radiological studies and biopsies served as benchmarks for the assessments.
      The impact of PSA level on WBS and SPECT results was also evaluated. RESULTS: The
      patient-based sensitivity, specificity, accuracy, PPV and NPV values of SPECT
      examinations were higher than those of WBS, especially in patients with serum PSA
      levels <40 ng/mL. CONCLUSION: Multi-FOV SPECT proved to be more sensitive and
      specific than WBS in detecting bone metastases in PCa patients.

PMID- 22158496
TI  - Immunohistochemical expression of Mum-1,  Oct-2 and Bcl-6 in systemic anaplastic
      large cell lymphomas.
AB  - AIMS AND BACKGROUND: Several transcription factors predominantly used for B-cell
      lineage identification are also expressed in a small percentage of T cells within
      germinal centers and interfollicular areas. The aim of the study was to evaluate
      the expression of Mum-1, Oct-2 and Bcl-6 in systemic anaplastic large cell
      lymphoma. METHODS: Thirty cases of anaplastic large cell lymphoma were retrieved
      from our archives and tissue microarray constructed. Immunohistochemistry was
      carried out using an avidin-biotin peroxidase complex method. RESULTS: A
      predominance of nuclear staining was observed for all transcription factors. Mum
      1 was positive in all but one case (96.7%). Half of the cases displayed Oct-2
      expression (15/30 cases). A considerable number of cases also had Bcl-6
      expression (9/30). Bcl-6 staining was noted to be more common in ALK positive
      cases. CONCLUSION: Our findings emphasize that these markers are not restricted
      to B-cell lineage and that extensive expression can be observed in anaplastic
      large cell lymphoma of T/null cell phenotype.

PMID- 22158497
TI  - Relationship between expression of vascular endothelial growth factor and
      intratumoral hemorrhage in human pituitary adenomas.
AB  - AIMS AND BACKGROUND: Although pituitary adenoma is a primary brain tumor that
      occasionally accompanies intratumoral hemorrhage, there are little reports about
      the molecular mechanism of intratumoral bleeding in pituitary adenoma. Vascular
      endothelial growth factor (VEGF) plays an important role in angiogenesis and
      vascular permeability of various brain tumors. The authors studied the
      relationship between intratumoral hemorrhage and the expression of VEGF in human
      pituitary adenomas. METHODS: VEGF expression was assessed by reverse
      transcriptase polymerase chain reaction (RT-PCR) in 71 pituitary adenomas.
      Clinical factors to investigate were age, gender, hormonal functioning, and
      radiological findings of pituitary adenomas. Radiological findings which were
      investigated by magnetic resonance (MR) images were intratumoral hemorrhage,
      cystic change, tumor size, and cavernous sinus invasion. The relationship between
      these factors and VEGF expression was statistically analyzed. RESULTS: VEGF was
      expressed in 25 cases (35.2%). Functioning tumors, hemorrhage, cystic change, and
      cavernous sinus invasion were 32 (45.1%), 18 (25.4%), 12 (16.9%), and 21 (29.6%)
      respectively. The expression of VEGF showed a significant relationship with the
      intratumoral hemorrhage of the adenomas (P <0.001). However, age, gender, tumor
      size, hormonal functioning, cyst formation, and cavernous sinus invasion had no
      relationship with VEGF expression (P >0.05). CONCLUSIONS: This study suggests
      that VEGF expression may be responsible for intratumoral hemorrhage of pituitary
      adenomas. Therefore, VEGF can be a novel target to prevent a catastrophic
      apoplexy in pituitary adenomas and to establish roles in angiogenesis-based
      therapeutics of pituitary adenomas.

PMID- 22158498
TI  - Influence of tumor cell culture supernatants on macrophage functional
      polarization: in vitro models of macrophage-tumor environment interaction.
AB  - AIMS AND BACKGROUND: Macrophages are heterogeneous cells with extensive
      functional plasticity; they can change their functional profiles repeatedly in
      response to environmental changes anywhere between their extreme phenotypical
      programs (labeled as M1 and M2 polarization, respectively). In terms of
      antitumoral immune response, M1 macrophages are considered to be beneficial,
      while M2 macrophages supposedly promote tumor progression. Tumor-associated
      macrophages (TAMs) represent a major leukocyte population present in many tumors.
      Although many studies indicate that TAMs elicit several M2-associated protumoral
      functions, including promotion of angiogenesis, matrix remodeling and suppression
      of adaptive immunity, their role regarding tumor progression is still
      controversial. The aim of the present study was to develop an appropriate in
      vitro model to study the effect of tumor-secreted soluble factors on the
      functional phenotype of macrophages. METHODS AND STUDY DESIGN: THP-1 human
      monocytic line cells and peripheral blood mononuclear cells from healthy
      volunteers were used for macrophage differentiation; primary tumor cell culture
      supernatants or tumor cell line supernatants were employed along with various
      cytokines, growth factors and other stimuli to design different model variants
      and to better mimic the in vivo tumor microenvironment. RESULTS: The cytokine
      secretion patterns of these macrophages suggest that primary tumor cell culture
      supernatants are able to switch the macrophage phenotype or to induce functional
      polarization of macrophages toward a mixed M1/M2 phenotype. Conclusions. These
      data support the hypothesis that TAM behavior is modulated by the tumor
      microenvironment itself.

PMID- 22158499
TI  - Preparation of anti-NYD-SP8 rabbit polyclonal antibody and its application in the
      analysis of NYD-SP8 expression in nasopharyngeal carcinoma cell lines and
      clinical tissues.
AB  - AIMS AND BACKGROUND: NYD-SP8 is a recently identified protein, the biological
      characteristics of which are still unclear. The aim of this study was to prepare
      an anti-NYD-SP8 rabbit polyclonal antibody and investigate the expression of NYD
      SP8 in human nasopharyngeal carcinoma cell lines and nasopharyngeal carcinoma
      tissues. METHODS: The anti-NYD-SP8 rabbit polyclonal antibody was prepared and
      ELISA was performed to assess the antibody titer. With this antibody, the NYD-SP8
      expression in four nasopharyngeal carcinoma cell lines, CNE1, CNE2, 5-8F and 6
      10B, was examined by Western blot and its expression in clinical tissues was also
      assessed by immunohistochemistry. RESULTS: The anti-NYD-SP8 rabbit polyclonal
      antibody with a high titer was successfully prepared. Western blot showed higher
      NYD-SP8 expression in CNE2 and 6-10B cells and lower expression in CNE1 and 5-8F
      cells. Immunohistochemistry demonstrated overexpression of NYD-SP8 in
      nasopharyngeal carcinoma tissue while the expression in normal nasopharyngeal
      tissue was negligible. CONCLUSIONS: Our anti-NYD-SP8 rabbit polyclonal antibody
      can be used both for Western blot and immunohistochemistry, and can be a valuable
      tool to investigate the function and distribution of NYD-SP8. The different NYD
      SP8 expression in various nasopharyngeal carcinoma cell lines indicated its
      complicated functions at different biological stages. The overexpression of NYD
      SP8 in clinical nasopharyngeal carcinoma tissue indicated that it could play an
      important role in nasopharyngeal carcinoma carcinogenesis.

PMID- 22158501
TI  - Pastoral care in hospitals: a literature review.
AB  - AIMS AND BACKGROUND: This literature review investigates the potential
      contribution of the pastoral care provided in hospitals by hospital chaplains, as
      part of an integrated view of patient care, particularly in institutions dealing
      with severe disease. METHODS AND STUDY DESIGN: A search was conducted in the
      Medline database covering the last 10 years. RESULTS: Ninety-eight articles were
      considered concerning the modern hospital chaplains' relationships and the
      principal procedures and practices associated with their roles, i.e., their
      relations with the scientific world, with other religious figures in the
      community, with other faiths and religious confessions, with other public health
      professionals and operators, with colleagues in professional associations and
      training activities, and with the hospital organization as a whole, as well as
      their patient assessment activities and the spiritual-religious support they
      provide, also for the patients' families. CONCLUSIONS: Improvements are needed on
      several fronts to professionalize the pastoral care provided in hospitals and
      modernize the figure of the hospital chaplain. These improvements include better
      relations between modern chaplains and the hospital organization and scientific
      world; more focus on a scientific approach to their activities and on evaluating
      the efficacy of pastoral care activities; greater clarity in the definition of
      the goals, methods and procedures; the design of protocols and a stance on
      important ethical issues; respect for the various faiths, different cultures and
      both religious and nonreligious or secularized customs; greater involvement in
      the multidisciplinary patient care teams, of which the hospital chaplains are an
      integral part; stronger integration with public health operators and cooperation
      with the psychosocial professions; specific training on pastoral care and
      professional certification of chaplains; and the development of shared ethical
      codes for the profession.

PMID- 22158500
TI  - The effect of 2-methoxyestradiol liposome on growth inhibition, angiogenesis and
      expression of VEGF and Ki67 in mice bearing H22 hepatocellular carcinoma.
AB  - AIMS AND BACKGROUND: 2-methoxyestradiol (2-ME), an endogenous metabolite of
      estrogen, has very low water solubility. It is currently in phase II clinical
      trials as both a chemopreventive and chemotherapeutic agent and has been orally
      administered to cancer patients. However, the poor oral absorption of the
      compound is one of the major obstacles for 2-ME development. Based on the
      molecular features of 2-ME, liposome can be considered an attractive formulation
      approach. Our purpose in this study is to research the antitumor efficacy of 2
      methoxyestradiol liposome (2-ME-L) in mice bearing H 22 tumors. METHODS: Murine
      H22 hepatocarcinoma served as an ectopic solid tumor model. The effects of
      antitumor therapy were evaluated by testing tumor growth, measuring the tumor
      inhibition rates in terms of weight and volume, and staining the tissues by
      hematoxylin and eosin. The synergistic mechanism of 2-ME-L therapy was elucidated
      by detecting changes in the expression of pathognostic factors in the tumor
      microenvironment. RESULTS: 2-ME-L significantly suppressed tumor growth. The
      morphological changes in the tumors indicated that the tumors in the treatment
      groups were effectively confined with little surrounding angiogenesis. Tumor
      cells of the treatment groups had abundant areas of necrosis with few nuclei in
      the mitotic phase. It was found that there was less immunohistochemical
      expression of vascular endothelial growth factor (VEGF), Ki67 and CD31 in the
      treatment groups and the efficacy of 2-ME-L was better than that of 2-ME solution
      (2-ME-S). This research demonstrated that 2-ME-L inhibited the growth of H 22
      tumors in a concentration-dependent manner and was more effective than 2-ME-S.
      CONCLUSIONS: 2-ME-L can suppress the growth of H22 solid tumors and has
      antiproliferative, proapoptotic and antiangiogenic activity. 2-ME-L could be of
      potential use in the treatment of hepatocellular carcinoma.

PMID- 22158502
TI  - Breast change perception in women after smoking cessation. A pilot study.
AB  - AIMS AND BACKGROUND: There are several barriers to smoking cessation that are
      unique to women. Compared to men, women report lower levels of motivation to quit
      and greater perceived difficulty with cessation. However, recent studies might
      favor commitment by women to quit through higher risk perception related e.g. to
      the development of premature facial wrinkling or the decrease in mammographic
      density due to cigarette smoking. METHODS: A pilot study to evaluate the
      perception of breast change after cessation and its possible motivational effect
      on maintenance was carried out. We interviewed 25 premenopausal women who had
      quit >=1 year before. We obtained information from the women and discussed
      changes in breast size and fullness. The two groups of women with and without
      breast change were statistically compared using the nonparametric Mann-Whitney
      test (continuous variables) and the Fisher test (categorical variables). RESULTS:
      Median age was 41 years (range, 30-49 years). Median carbon monoxide (CO) before
      quitting was 18 ppm and median pack years (PY) was 22.5; both parameters
      characterize a category of mild smokers. Sixteen women (64%) reported breast
      changes 6 months after quitting smoking. This outcome was paralleled by only
      moderate effects on weight or body mass index (BMI) increase after quitting.
      Notably, of the 16 women with breast change, only 3 (19%) with a normal baseline
      BMI showed a BMI increase to >25. CONCLUSIONS: Within the limitations of the
      small size of a pilot study, these results indicate that premenopausal women
      experience subjective perception of change in breast size after smoking
      cessation, which may not be totally explained by weight gain. Further studies are
      needed to understand the effect, if any, of such perception on the motivation to
      quit smoking.

PMID- 22158503
TI  - MUTYH-associated colon disease: adenomatous polyposis is only one of the possible
      phenotypes. A family report and literature review.
AB  - AIMS AND BACKGROUND: The MutY human homologue gene (MUTYH) is responsible for
      about a quarter of attenuated familial adenomatous polyposis. Occasionally, it
      has been associated with hyperplastic polyps and serrated adenoma. We report a
      family where the same MUTYH mutation determined four different phenotypes,
      including a case of hyperplastic polyposis syndrome. PATIENTS AND METHODS: A
      family with a history of right-sided colon cancer and multiple colonic polyposis
      was investigated. Genetic tests were correlated with clinical findings to define
      phenotypic manifestations of MUTYH mutations. The pertinent English-language
      literature was reviewed to evaluate the risk of malignancy of MUTYH and the role
      of prophylactic surgery. RESULTS: Three male siblings carried a biallelic MUTYH
      mutation (G382D-exon13), while the fourth was heterozygote. One developed an
      isolated cecal cancer at the age of 48. Another, aged 38, was diagnosed with
      numerous minute colonic and rectal polyps and underwent a proctocolectomy, with
      final pathology showing a picture of hyperplastic and lymphoid polyposis. The
      third biallelic brother, 46 years old, developed four hyperplastic lesions, while
      the heterozygote brother had a large flat serrated adenoma of the right colon
      removed at the age of 50. CONCLUSION: Many aspects of MUTYH mutation still need
      to be clarified and one of them regards the different phenotypic expressions.
      Although the majority of reported cases manifested attenuated adenomatous
      polyposis, hyperplastic polyps and serrated adenomas appear to be more common
      than expected. Presenting hyperplastic polyposis syndrome is very unusual and may
      represent a clinical dilemma for correct management. Current evidence suggests to
      handle MUTYH-associated polyposis as typical FAP.

PMID- 22158504
TI  - Orthotopic ileal neobladder reconstruction  in a woman who developed squamous 
      cell carcinoma of the urinary bladder after kidney transplantation.
AB  - The case of a 62-year-old woman who developed squamous cell carcinoma of the
      bladder 16 years after a kidney transplant is reported here. After the
      transplant, immunosuppressive therapy was maintained with cyclosporin A (200
      mg/day) and the patient's serum creatinine level was 0.9 mg/dL. She was diagnosed
      with squamous cell carcinoma of the bladder 16 years later and underwent radical
      cystectomy with an orthotopic ileal neobladder. The Studer technique was used and
      the afferent ileal loop was anastomosed to the graft ureter. The postoperative
      course was uneventful. At the 6-month follow-up visit, the patient showed no
      evidence of recurrence. Her serum creatinine level was 1.0 mg/dL. The patient was
      continent during the day and the night. This case shows that the construction of
      an orthotopic ileal neobladder after cystectomy is safe and feasible in kidney
      transplant recipients.

PMID- 22158505
TI  - A case of thyroid metastasis of nasopharyngeal cancer.
AB  - AIMS AND BACKGROUND: Thyroid metastasis from nasopharyngeal carcinoma is a rare
      occurrence. We report a case of thyroid metastases from nasopharyngeal carcinoma
      with a review of the literature. METHODS: In April 2007 a 59-year-old man was
      diagnosed with nasopharyngeal carcinoma; in October 2009 he underwent a thyroid
      biopsy that revealed G2 infiltrating spinocellular carcinoma with lymph node
      involvement. He was treated with chemotherapy and radiotherapy at our institute.
      RESULTS: Currently, after 6 cycles of adjuvant chemotherapy with taxotere and
      gemcitabine, the patient is asymptomatic with stable disease and improved quality
      of life. CONCLUSION: According to the literature, the treatment choice depends on
      clinical disease extent. Surgery and/or chemo-radiation therapy must therefore be
      tailored to the individual patient in order to improve clinical outcome and
      quality of life.

PMID- 22158506
TI  - Primary adrenal gland carcinosarcoma associated  with metastatic rectal cancer: a
      hitherto unreported collision tumor.
AB  - In this report we describe the case of a young woman with familial adenomatous
      polyposis who developed metastatic rectal cancer during pregnancy. At diagnosis,
      we decided to perform a transabdominal laparoscopic adrenalectomy, because of the
      high risk of bowel obstruction, and to define the origin of the adrenal gland
      lesion, suspected to be primary on the basis of imaging results. The histological
      specimen showed a collision tumor between an adrenal metastasis of a rectal tumor
      and a primary adrenal gland carcinosarcoma. The peculiarity of the case is due
      not only to its clinical presentation during pregnancy, but also to the presence
      of this uncommon adrenal collision tumor. A particular challenge for the
      clinician is to define the priority between these two tumors: the presence of two
      distinct and colliding aggressive neoplasms poses a problem in the choice of the
      best therapeutic approach, also given the impossibility to biopsy all metastatic
      sites. However, we decided to treat the patient as having a metastatic rectal
      cancer, because we had a solid histological confirmation of metastases.

PMID- 22158508
TI  - Unusual giant cell tumor of a floating rib: a case report.
AB  - Giant cell tumor is an unusual neoplasm of the ribs. Herein is presented the case
      of a patient with an abdominal wall mass, which turned out to be a giant cell
      tumor of the 11th rib. This is a very uncommon site for a giant cell tumor, which
      also had a peculiar shape. No other similar case has been reported in the medical
      literature.

PMID- 22158507
TI  - Hemolytic uremic syndrome induced by infusion of oxaliplatin: a case report.
AB  - INTRODUCTION: Oxaliplatin is a third-generation platinum compound with proven
      antitumor activity in the treatment of colorectal cancer. The occurrence of life
      threating hemolitic uremic syndrome has been observed after oxaliplatin therapy.
      The kind of tumor and treatment modalities seem to influence the onset of
      hemolitic uremic syndrome. METHODS: The clinical course of the case is reviewed
      and compared with reports of other similar cases in the literature. RESULTS: We
      describe the development of hemolitic uremic syndrome as a result of prolonged
      oxaliplatin treatment of a colon cancer patient. CONCLUSIONS: Although this rare
      event requires the concurrence of other unknown factors, it should be considered
      in a decision-making setting.

PMID- 22158509
TI  - Morphological and tissue characterization of the medicinal fungus Hericium
      coralloides by a structural and molecular imaging platform.
AB  - In this study the potential of new imaging techniques such as Magnetic Resonance
      Imaging (MRI), Matrix-Assisted Laser Desorption/Ionization (MALDI) profiling mass
      spectrometry ("MALDI Profiling") and Fourier Transform Infrared (FTIR)
      spectroscopic imaging was evaluated to study morphological and molecular patterns
      of the potential medicinal fungus Hericium coralloides. For interpretation, the
      MALDI profiling, FTIR imaging and MRI results were correlated with histological
      information gained from Scanning Electron Microscopy (SEM) and Light Microscopy
      (LM). Additionally we tested several evaluation processes and optimized the
      methodology for use of complex FTIR images to monitor molecular patterns. It is
      demonstrated that the combination of these spectroscopic methods enables to gain
      a more distinct picture concerning morphology and distribution of active
      ingredients. We were able to obtain high quality FTIR imaging and MALDI-profiling
      results and to distinguish different tissue types with their chemical
      ingredients. Beside this, we have created a 3-D reconstruction of a mature
      Hericium basidioma, based on the MRI dataset: analyses allowed, for the first
      time, a realistic approximation of the "evolutionary effectiveness" of this
      bizarrely formed basidioma type, concerning the investment of sterile tissue and
      its reproductive output (production of basidiospores).

PMID- 22158510
TI  - Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin
      expressing interneurons.
AB  - Epilepsy is a common and refractory neurological disorder, but the neuronal
      regulatory mechanisms of epileptogenesis remain largely unclear. Activity
      dependent transcription of genes for neurotrophins such as brain-derived
      neurotrophic factor (BDNF) has been shown to promote epileptogenesis; however,
      little is known about factors that may act as intrinsic, homeostatic or
      counterbalancing mechanisms. Using rodent models, here we show that limbic
      seizure activity upregulated NRG1-ErbB4 signaling and that epileptogenesis was
      inhibited by infusing NRG1 intracerebrally but exacerbated by neutralizing
      endogenous NRG1 with soluble ErbB4 extracellular domain, by inhibiting ErbB4
      activation or by deleting the Erbb4 gene. Furthermore, specific depletion of
      ErbB4 in parvalbumin-expressing interneurons abolished NRG1-mediated inhibition
      of epileptogenesis and promoted kindling progression, resulting in increased
      spontaneous seizures and exuberant mossy fiber sprouting. In contrast, depleting
      ErbB4 in CaMKIIalpha-positive pyramidal neurons had no effect. Thus, NRG1-induced
      activation of ErbB4 in parvalbumin-expressing inhibitory interneurons may serve
      as a critical endogenous negative-feedback mechanism to suppress limbic
      epileptogenesis.

PMID- 22158511
TI  - Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and
      acts in epilepsy.
AB  - Dysfunction of fast-spiking, parvalbumin-positive (FS-PV) interneurons is
      implicated in the pathogenesis of epilepsy. ErbB4, a key Neuregulin 1 (NRG1)
      receptor, is mainly expressed in this type of interneurons, and recent studies
      suggest that parvalbumin interneurons are a major target of NRG1-ErbB4 signaling
      in adult brain. Thus, we hypothesized that downregulation of NRG1-ErbB4 signaling
      in FS-PV interneurons is involved in epilepsy. We found that NRG1, through its
      receptor ErbB4, increased the intrinsic excitability of FS-PV interneurons. This
      effect was mediated by increasing the near-threshold responsiveness and
      decreasing the voltage threshold for action potentials through Kv1.1, a voltage
      gated potassium channel. Furthermore, mice with specific deletion of ErbB4 in
      parvalbumin interneurons were more susceptible to pentylenetetrazole- and
      pilocarpine-induced models of epilepsy. Exogenous NRG1 delayed the onset of
      seizures and decreased their incidence and stage. Moreover, expression of ErbB4,
      but not ErbB2, was downregulated in human epileptogenic tissue. Together, our
      findings suggest that NRG1-ErbB4 signaling contributes to human epilepsy through
      regulating the excitability of FS-PV interneurons. ErbB4 may be a new target for
      anticonvulsant drugs in epilepsy.

PMID- 22158512
TI  - Coactivation of thalamic and cortical pathways induces input timing-dependent
      plasticity in amygdala.
AB  - Long-term synaptic enhancements in cortical and thalamic auditory inputs to the
      lateral nucleus of the amygdala (LAn) mediate encoding of conditioned fear
      memory. It is not known, however, whether the convergent auditory conditioned
      stimulus (CSa) pathways interact with each other to produce changes in their
      synaptic function. We found that continuous paired stimulation of thalamic and
      cortical auditory inputs to the LAn with the interstimulus delay approximately
      mimicking a temporal pattern of their activation in behaving animals during
      auditory fear conditioning resulted in persistent potentiation of synaptic
      transmission in the cortico-amygdala pathway in rat brain slices. This form of
      input timing-dependent plasticity (ITDP) in cortical input depends on inositol
      1,4,5-trisphosphate (InsP(3))-sensitive Ca(2+) release from internal stores and
      postsynaptic Ca(2+) influx through calcium-permeable kainate receptors during its
      induction. ITDP in the auditory projections to the LAn, determined by
      characteristics of presynaptic activity patterns, may contribute to the encoding
      of the complex CSa.

PMID- 22158513
TI  - TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy
      through GAT-3.
AB  - Astrocytes contribute to the formation and function of synapses and are found
      throughout the brain, where they show intracellular store-mediated Ca(2+)
      signals. Here, using a membrane-tethered, genetically encoded calcium indicator
      (Lck-GCaMP3), we report the serendipitous discovery of a new type of Ca(2+)
      signal in rat hippocampal astrocyte-neuron cocultures. We found that Ca(2+)
      fluxes mediated by transient receptor potential A1 (TRPA1) channels gave rise to
      frequent and highly localized 'spotty' Ca(2+) microdomains near the membrane that
      contributed appreciably to resting Ca(2+) in astrocytes. Mechanistic evaluations
      in brain slices showed that decreases in astrocyte resting Ca(2+) concentrations
      mediated by TRPA1 channels decreased interneuron inhibitory synapse efficacy by
      reducing GABA transport by GAT-3, thus elevating extracellular GABA. Our data
      show how a transmembrane Ca(2+) source (TRPA1) targets a transporter (GAT-3) in
      astrocytes to regulate inhibitory synapses.

PMID- 22158515
TI  - Longitudinal evaluation of mouse hind limb bone loss after spinal cord injury
      using novel, in vivo, methodology.
AB  - Spinal cord injury (SCI) is often accompanied by osteoporosis in the sublesional
      regions of the pelvis and lower extremities, leading to a higher frequency of
      fractures. As these fractures often occur in regions that have lost normal
      sensory function, the patient is at a greater risk of fracture-dependent
      pathologies, including death. SCI-dependent loss in both bone mineral density
      (BMD, grams/cm2) and bone mineral content (BMC, grams) has been attributed to
      mechanical disuse, aberrant neuronal signaling and hormonal changes. The use of
      rodent models of SCI-induced osteoporosis can provide invaluable information
      regarding the mechanisms underlying the development of osteoporosis following SCI
      as well as a test environment for the generation of new therapies. Mouse models
      of SCI are of great interest as they permit a reductionist approach to mechanism
      based assessment through the use of null and transgenic mice. While such models
      have provided important data, there is still a need for minimally-invasive,
      reliable, reproducible, and quantifiable methods in determining the extent of
      bone loss following SCI, particularly over time and within the same cohort of
      experimental animals, to improve diagnosis, treatment methods, and/or prevention
      of SCI-induced osteoporosis. An ideal method for measuring bone density in
      rodents would allow multiple, sequential (over time) exposures to low-levels of X
      ray radiation. This study describes the use of a new whole-animal scanner, the
      IVIS Lumina XR (Caliper Instruments) that can be used to provide low-energy (1-3
      milligray (mGy)) high-resolution, high-magnification X-ray images of mouse hind
      limb bones over time following SCI. Significant bone density loss was seen in the
      tibiae of mice by 10 days post-spinal transection when compared to uninjured, age
      matched control (naive) mice (13% decrease, p < 0.0005). Loss of bone density in
      the distal femur was also detectable by day 10 post-SCI, while a loss of density
      in the proximal femur was not detectable until 40 days post injury (7% decrease,
      p < 0.05). SCI-dependent loss of mouse femur density was confirmed post-mortem
      through the use of Dual-energy X-ray Absorptiometry (DXA), the current "gold
      standard" for bone density measurements. We detect a 12% loss of BMC in the
      femurs of mice at 40 days post-SCI using the IVIS Lumina XR. This compares
      favorably with a previously reported BMC loss of 13.5% by Picard and colleagues
      who used DXA analysis on mouse femurs post-mortem 30 days post-SCI (9). Our
      results suggest that the IVIS Lumina XR provides a novel, high-resolution/high
      magnification method for performing long-term, longitudinal measurements of hind
      limb bone density in the mouse following SCI.

PMID- 22158516
TI  - Bone marrow of multiorgan donors underutilized:  implications for improvement of
      accessibility of hematopoietic cells for transplantations.
AB  - BACKGROUND: The demand for human hematopoietic stem and progenitor cells (HSPCs)
      for transplantation is increasing. Thus, effective alternative sources of HSPCs
      are required. Consequently, we sought to expand the accessibility of
      hematopoietic cells for clinical purposes by the investigation of hematopoietic
      reconstitution after transplantation of human HSPCs harvested from the bone
      marrow (BM) of heparinized deceased organ donors (HDODs). METHODS: For multipart
      research comparison, human BM HDODs-, healthy donor-derived, umbilical cord blood
      nuclear cells, or CD34(+) cells were transplanted into sublethally irradiated
      NOD/SCID mice. Twenty-eight days after transplantation nuclear cells were
      isolated from the murine BM, spleen, and peripheral blood and were used to
      quantitatively detect human CD45 antigen by quantitative real-time reverse
      transcriptase-polymerase chain reaction and flow cytometry. The clonogenic growth
      of human colony-forming units was also investigated. RESULTS: We found that
      umbilical cord blood-derived HSPCs showed the greatest transplantation potential
      in our in vivo model. Interestingly, the transplantation potential of HSPCs
      collected from the BM of HDODs was of the same quality as cells obtained from
      healthy BM donors. CONCLUSION: Based on these results, we conclude that HDODs are
      a strongly underappreciated source of HSPCs that are ready to use for clinical
      purposes.

PMID- 22158514
TI  - GABAergic circuits mediate the reinforcement-related signals of striatal
      cholinergic interneurons.
AB  - Neostriatal cholinergic interneurons are believed to be important for
      reinforcement-mediated learning and response selection by signaling the
      occurrence and motivational value of behaviorally relevant stimuli through
      precisely timed multiphasic population responses. An important problem is to
      understand how these signals regulate the functioning of the neostriatum. Here we
      describe the synaptic organization of a previously unknown circuit that involves
      direct nicotinic excitation of several classes of GABAergic interneurons,
      including neuroptide Y-expressing neurogilaform neurons, and enables cholinergic
      interneurons to exert rapid inhibitory control of the activity of projection
      neurons. We also found that, in vivo, the dominant effect of an optogenetically
      reproduced pause-excitation population response of cholinergic interneurons was
      powerful and rapid inhibition of the firing of projection neurons that is
      coincident with synchronous cholinergic activation. These results reveal a
      previously unknown circuit mechanism that transmits reinforcement-related
      information of ChAT interneurons in the mouse neostriatal network.

PMID- 22158518
TI  - Translational stem cell therapy for amyotrophic lateral sclerosis.
AB  - Effective treatments are urgently needed for amyotrophic lateral sclerosis (ALS),
      a fatal neurodegenerative disease characterized by the loss of motor neurons. In
      2009, the FDA approved the first phase I safety trial of direct intraspinal
      transplantation of neural stem cells into patients with ALS, which is currently
      in progress. Stem cell technologies represent a promising approach for treating
      ALS, but several issues must be addressed when translating promising experimental
      ALS therapies to patients. This article highlights the key research that supports
      the use of stem cells as a therapy for ALS, and discusses the rationale behind
      and approach to the phase I trial. Completion of the trial could pave the way for
      continued advances in stem cell therapy for ALS and other neurodegenerative
      diseases.

PMID- 22158517
TI  - Hepatocyte growth factor sustains T regulatory cells and prolongs the survival of
      kidney allografts in major histocompatibility complex-inbred CLAWN-miniature
      swine.
AB  - BACKGROUND: Although 12 days of high dose of FK506 permits the induction of
      tolerance of fully major histocompatibility complex (MHC)-mismatched allogeneic
      kidneys in MGH-miniature swine, we found that the same dose of FK506 is
      insufficient to induce such tolerance CLAWN-miniature swine. The CLAWN swine
      model was therefore chosen to study the potential immunoregulatory effects of
      human-recombinant hepatocyte growth factor (HGF). METHODS: Ten CLAWN miniature
      swine received fully MHC-mismatched kidneys with 12 days (days 0-11) of FK506.
      Among these 10 recipients, 4 received 7 or 14 days of human-recombinant HGF
      starting at day 11. Graft function was assessed by daily serum creatinine and
      biopsies. Immunologic assays, including CD4/CD25 DP and FoxP3+ cells and
      development of antidonor antibodies, were performed. RESULTS: Without HGF, all
      six CLAWN recipients developed severe acute rejection (Cre >9 mg/dL) within 3
      weeks of transplantation. In contrast, in the four animals that received HGF for
      7 to 14 days, stable renal function was observed for more than 50 days, although
      all grafts were ultimately rejected by postoperative day 80. Percent FoxP3+ cells
      in the CD4+CD25+ double positive population (T regulatory cells) in peripheral
      blood monocyte cells decreased in recipients with FK506 induction monotherapy
      while no reduction was observed in recipients treated with FK506 and HGF.
      CONCLUSION: This study demonstrates that in CLAWN swine treated with a dose of
      FK506 insufficient to induce tolerance across a fully MHC mismatched barrier, a
      short course of HGF may inhibit acute rejection while maintaining T regulatory
      cells. To our knowledge, this study provides the first evidence in a large animal
      transplantation model of HGF's immunoprotective effects.

PMID- 22158519
TI  - Optimization and characterization of liposome formulation by mixture design.
AB  - This study presents the application of the mixture design technique to develop an
      optimal liposome formulation by using the different lipids in type and percentage
      (DOPC, POPC and DPPC) in liposome composition. Ten lipid mixtures were generated
      by the simplex-centroid design technique and liposomes were prepared by the
      extrusion method. Liposomes were characterized with respect to size, phase
      transition temperature, zeta-potential, lamellarity, fluidity and efficiency in
      loading calcein. The results were then applied to estimate the coefficients of
      mixture design model and to find the optimal lipid composition with improved
      entrapment efficiency, size, transition temperature, fluidity and zeta-potential
      of liposomes. The response optimization of experiments was the liposome
      formulation with DOPC: 46%, POPC: 12% and DPPC: 42%. The optimal liposome
      formulation had an average diameter of 127.5 nm, a phase-transition temperature
      of 11.43  degrees C, a zeta-potential of -7.24 mV, fluidity (1/P)(TMA-DPH)((!))
      value of 2.87 and an encapsulation efficiency of 20.24%. The experimental results
      of characterization of optimal liposome formulation were in good agreement with
      those predicted by the mixture design technique.

PMID- 22158520
TI  - Heart Rate Variability and Respiratory Sinus Arrhythmia Assessment of Affective
      States by Bivariate Autoregressive Spectral Analysis.
AB  - The study of emotions elicited by human-computer interactions is a promising
      field that could lead to the identification of specific patterns of affective
      states. We present a heart rate variability (HRV) assessment of the autonomic
      nervous system (ANS) response and respiratory sinus arrhythmia during PC-mediated
      stimuli by means of standard and multivariate autoregressive spectral methods. 35
      healthy volunteers were exposed to computer-mediated tasks during data
      collection. The stimuli were designed to elicit: relaxation (R), engagement (E)
      and stress (S); half of the subjects were exposed to E before S (RES) while the
      other to S before E (RSE). HRV measures clearly separate the ANS response among
      R, S and E. Less significant differences are found between E and S in RSE,
      suggesting that S stimuli may cause a lasting response affecting the E period.
      Results from the bivariate analysis indicate a disruption of the cardio
      respiratory coupling during non-relax conditions.

PMID- 22158521
TI  - Expressing human interleukin-15 from oncolytic vesicular stomatitis virus
      improves survival in a murine metastatic colon adenocarcinoma model through the
      enhancement of anti-tumor immunity.
AB  - In this study, we sought to enhance the potency of an oncolytic virus, vesicular
      stomatitis virus (VSV), by inserting a transgene encoding a highly secreted
      version of human interleukin-15 (IL-15). IL-15 has shown promise as an
      immunotherapeutic cytokine, as it is able to enhance both natural killer (NK) and
      T-cell responses, but it has not yet been tested as a therapeutic transgene in
      the context of viral oncolysis. The transgene was modified to ensure enhanced
      secretion of IL-15 from infected cells, leading to strong localized expression
      from infected CT-26 tumors in vivo. This localized expression in the tumor
      microenvironment led to a clear enhancement to anti-tumoral T-cell responses and
      enhanced survival, while additional IL-15 administration systemically failed to
      further enhance the therapy. Overall, the transient localized expression of IL-15
      in the tumour by an oncolytic virus was able to induce stronger anti-tumoral
      immunity in a murine model of colon carcinoma.

PMID- 22158522
TI  - The antitumor effects of adenoviral-mediated, intratumoral delivery of
      interleukin 23 require endogenous IL-12.
AB  - Interleukin (IL)-23 is a member of the IL-12 family of heterodimeric cytokines,
      comprised of p19 and p40 subunits, which exhibits immunostimulatory properties
      similar to IL-12. We have demonstrated previously that adenoviral-mediated,
      intratumoral delivery of IL-23 (Ad.IL-23) was able to induce systemic antitumor
      immunity. Here we demonstrate that Ad.IL-23 requires endogenous IL-12 for
      conferring an antitumor effect after adenoviral-mediated, intratumoral delivery.
      In contrast, Ad.IL-12 does not require IL-23 for its antitumor effects although
      endogenous IL-23 appears important for induction of systemic antitumor immunity
      by IL-12. However, despite the requirement for endogenous IL-12, co-delivery of
      IL-23 and IL-12 does not provide even an additive local or systemic antitumor
      effect, regardless of the dose. We further demonstrate that although the use of a
      single-chain IL-23 (scIL-23) results in higher level of expression and a more
      pronounced IL-23-mediated antitumor effect, there is still no synergy with IL-12.
      These results demonstrate that although significant antitumor effects are
      achieved by intratumoral injection of adenovirus expressing either scIL-23 or IL
      12 alone and that IL-23 requires endogenous IL-12 for maximum antitumor benefit,
      the combined use of these cytokines provides no additive or synergistic effect.

PMID- 22158523
TI  - Mc-hES, a novel plasmid carrying human endostatin gene, inhibits nasopharyngeal
      carcinoma growth.
AB  - Conventional plasmids for gene therapy produce low-level and short-term gene
      expression. Here, we first created minicircle carrying endostatin (mc-hES) for
      measurement of transfection efficiency. Compared with pcDNA-hES, MC-mediated
      endostatin gene transfer in vitro resulted in seven-fold greater endostatin
      expression levels in transfected cells and inhibited the growth of Human
      umbilical vein endothelial cells (HUVEC) more efficiently. HUVEC cell migration
      and tube-formation assays suggested that MC-mediated endostatin gene has
      significant anti-migration and anti-tube-formation capacity than that in pcDNA
      hES. In vivo experiments showed that after transfection, mc-hES inhibited the
      growth of nasopharyngeal carcinoma xenografts. The tumor inhibition rates of mc
      hES and pcDNA-hES were 60.8% and 26.9%, respectively (P<0.05). MC-mediated
      intratumoral endostatin expression in vivo was 2.2-17.9 times higher than pcDNA
      hES in xenografted mice and lasted for 20 days. Our results suggest that
      minicircle DNA vectors might be a promising vector for biotherapy and should be
      further investigated.

PMID- 22158525
TI  - Short answer question case series: diagnosis of acute cholecystitis.

PMID- 22158524
TI  - Characterization of a PDK1 homologue from the moss Physcomitrella patens.
AB  - The serine/threonine protein kinase 3-phosphoinositide-dependent protein kinase 1
      (PDK1) is a highly conserved eukaryotic kinase that is a central regulator of
      many AGC kinase subfamily members. Through its regulation of AGC kinases, PDK1
      controls many basic cellular processes, from translation to cell survival. While
      many of these PDK1-regulated processes are conserved across kingdoms, it is not
      well understood how PDK1 may have evolved within kingdoms. In order to better
      understand PDK1 evolution within plants, we have isolated and characterized the
      PDK1 gene from the moss Physcomitrella patens (PpPDK1), a nonvascular
      representative of early land plants. PpPDK1 is similar to other plant PDK1s in
      that it can functionally complement a yeast PDK1 knockout line. However, unlike
      PDK1 from other plants, the P. patens PDK1 protein does not bind phospholipids
      due to a lack of the lipid-binding pleckstrin homology domain, which is used for
      lipid-mediated regulation of PDK1 activity. Sequence analysis of several PDK1
      proteins suggests that lipid regulation of PDK1 may not commonly occur in algae
      and nonvascular land plants. PpPDK1 can phosphorylate AGC kinase substrates from
      tomato (Solanum lycopersicum) and P. patens at the predicted PDK1 phosphorylation
      site, indicating that the PpPDK1 substrate phosphorylation site is conserved with
      higher plants. We have also identified residues within the PpPDK1 kinase domain
      that affect kinase activity and show that a mutant with highly reduced kinase
      activity can still confer cell viability in both yeast and P. patens. These
      studies lay the foundation for further analysis of the evolution of PDK1 within
      plants.

PMID- 22158526
TI  - Short answer question case series: chest pain in the healthy young male.

PMID- 22158528
TI  - Short answer question case series: management of cocaine-associated chest pain.

PMID- 22158527
TI  - A retrospective cohort study to re-evaluate clinical correlates for intracranial
      injury in minor head injury.
AB  - INTRODUCTION: The aim of this study was to determine the Relative Risk (RR)
      ratios for common clinical correlates in adult patients with minor head injury in
      a cohort of patients in which loss of consciousness (LOC) and post-traumatic
      amnesia (PTA) were not the only entry criteria for CT scanning. METHODS: The
      computerised CT request notes were reviewed on all patients who underwent a CT
      head scan with a minor head injury over a 1-year period (January 2009-December
      2009). The clinical signs and symptoms at presentation were extracted from the
      request notes and the RR ratios were calculated for five clinical correlates:
      LOC, PTA, vomiting, nausea and headache. RESULTS: 456 Glasgow coma scale (GCS) 15
      patients underwent CT scanning during the period January 2009-December 2009. 55
      of the 456 patients had positive CT findings (12%). 270 patients (59%) of the GCS
      15 cohort had neither LOC nor PTA and of this subgroup 27 had positive scans. LOC
      was the only clinical correlate in which the RR reached statistical significance;
      RR 2.0930 (95% CI 1.25 to 3.50). However, vomiting accounted for four cases,
      headache for four cases and nausea for no cases. CONCLUSIONS: Using LOC or PTA as
      the principal entry criterion for CT scanning may result in a significant number
      of patients with traumatic intracranial injury being missed. Using a less
      stringent approach still achieved an acceptable CT abnormality rate.

PMID- 22158529
TI  - Randomised controlled crossover trial of the effect on PtCO2 of oxygen-driven
      versus air-driven nebulisers in severe chronic obstructive pulmonary disease.
AB  - BACKGROUND: The comparative safety of oxygen versus air-driven nebulised
      bronchodilators in patients with acute exacerbations of chronic obstructive
      pulmonary disease (COPD) is uncertain. A randomised controlled trial was
      performed to assess the effect on the arterial partial pressure of carbon dioxide
      of nebulised bronchodilator driven with oxygen versus air in stable severe COPD.
      METHODS: In an open label randomised study, 18 subjects with stable severe COPD
      attended on 2 days to receive nebulised bronchodilator therapy driven by air or
      oxygen. Subjects received 5 mg salbutamol and 0.5 mg ipratropium bromide by
      nebulisation over 15 min, then, after 5 min, 5 mg salbutamol nebulised over 15
      min, followed by 15 min of observation. Transcutaneous carbon dioxide tension
      (PtCO(2)) and oxygen saturations were recorded at 5 min intervals during the
      study. The primary outcome was the PtCO(2) after the completion of the second
      bronchodilator treatment. RESULTS: PtCO(2) was higher with nebulised
      bronchodilator therapy delivered by oxygen, but decreased back to the level
      associated with air nebulisation 15 min after completion of the second nebulised
      dose. One subject experienced an increase in PtCO(2) of 11 mm Hg after the first
      bronchodilator nebulisation driven by oxygen. The mean PtCO(2) difference between
      the oxygen and air groups after the second nebulisation was 3.1 mm Hg (95% CI 1.6
      to 4.5, p<0.001). CONCLUSION: Nebulisers driven with oxygen result in
      significantly higher levels of PtCO(2) than those driven with air in patients
      with severe COPD. CLINICAL TRIAL REGISTRATION NUMBER: The study was registered on
      the Australian New Zealand Clinical Trials Registry (ACTRN12610000080022).

PMID- 22158530
TI  - Rescuers may vary their side of approach to a casualty without impact on
      cardiopulmonary resuscitation performance.
AB  - AIM: To determine whether cardiopulmonary resuscitation (CPR) performance is
      influenced by a rescuer's preferred side of approach. METHODS: Eighty-three first
      year healthcare students were enrolled in a prospective randomised crossover
      study comparing chest compression quality during uninterrupted chest compression
      CPR after approach from both their preferred and non-preferred sides. RESULTS:
      Chest compression quality was not dependent on rescuers' sidedness preference;
      neither mean compression rate and depth nor hand positioning differed between
      sides of approach. CONCLUSIONS: No link exists between the side from which a
      rescuer approaches, or prefers to approach, a casualty and chest compression
      quality.

PMID- 22158531
TI  - Emergency triage, assessment and treatment at a district hospital in Malawi.
AB  - Rumphi District Hospital in Northern Malawi had no emergency triage, assessment
      or treatment system for the over 5 year olds. Eighty healthcare workers were
      trained on the South African Triage Scale, which was then implemented within a
      modified outpatient department. Provision of medical equipment and construction
      of an emergency room took place to allow early life saving treatment.

PMID- 22158532
TI  - Short answer question case series: diagnosis and management of glaucoma.

PMID- 22158533
TI  - Dexmedetomidine in the emergency department: assessing safety and effectiveness
      in difficult-to-sedate acute behavioural disturbance.
AB  - OBJECTIVES: To investigate the safety and effectiveness of dexmedetomidine for
      sedating patients in whom previous attempts at sedation in the emergency
      department have failed. METHODS: A study was carried out on dexmedetomidine for
      sedation of patients with acute behavioural disturbance for whom at least two
      previous attempts at sedation with other drugs had failed. Either a loading dose
      of dexmedetomidine was administered or a loading dose then an infusion.
      Administration was titrated to the sedative effect and vital signs. The sedation
      assessment tool was used to assess effectiveness, and adverse effects were
      recorded. Effective sedation was defined as a fall in the sedation assessment
      tool by two levels or more for an hour or more. RESULTS: A total of 13 patients
      were given dexmedetomidine. Five of the 13 had a loading dose only. Of these
      five, successful sedation was achieved in two, and the other three were only
      briefly sedated during the loading dose. One patient had hypotension. Eight
      patients received an infusion after the loading dose. Three were successfully
      sedated, but one developed hypotension. Four patients required a decrease in the
      infusion rate for hypotension, and in three of these the rate decrease
      compromised the sedation and one of these required intubation for sedation. The
      final patient had persistent acute behavioural disturbance, which required
      intubation for management. Five of the eight patients developed hypotension, and,
      of the five, one had bradycardia and one went into atrial fibrillation.
      CONCLUSION: Intravenous dexmedetomidine for difficult-to-sedate patients with
      acute behavioural disturbance is not safe in the emergency department setting.

PMID- 22158534
TI  - Validating the acute heart failure index for patients presenting to the emergency
      department with decompensated heart failure.
AB  - BACKGROUND: The acute heart failure index (AHFI) is a previously derived
      prediction rule to identify patients presenting to emergency departments (ED)
      with decompensated heart failure (DHF) at low risk of early life-threatening
      events. STUDY OBJECTIVES: To validate the AHFI prospectively. METHODS: Using a
      prospective cohort study, adult patients presenting to an urban university
      hospital ED with DHF were included. Data on 21 variables were gathered to
      calculate the AHFI. Primary endpoints included inpatient death and non-fatal
      serious outcomes (myocardial infarction, ventricular fibrillation, cardiogenic
      shock, cardiac arrest, intubation, or cardiac reperfusion). Secondary endpoints
      included death from any cause or readmission for heart failure within 30 days.
      Primary and secondary endpoint rates were calculated with 95% CI for the low and
      higher-risk subgroups. RESULTS: 259 patients were enrolled. 245/259 (95%) were
      admitted. 60/259 (23%) met low-risk criteria, of whom 1/60 (1.7%, CI 0.04 to 8.9)
      was discharged after sustaining pulseless electrical activity arrest. The
      comparable primary outcome rate in the derivation study was 1.4% (CI 1.1 to 1.7).
      17/199 (8.5%, CI 5.1 to 13.3) higher-risk patients experienced an endpoint,
      compared with 13.3% (CI 12.9 to 13.7) in the derivation cohort. One low-risk
      patient (1.7%, CI 0.04 to 8.9) died within 30 days, and five (8.3%, CI 2.8 to
      18.4) were readmitted. Corresponding rates in the derivation study were 2% and
      5%, respectively. CONCLUSION: The results are consistent with those previously
      reported for the low-risk subgroup of the AHFI. Further research is needed to
      determine the impact, safety and full range of generalisability of the AHFI as an
      adjunct to decision making.

PMID- 22158535
TI  - Safety and efficiency of triaging low urgent self-referred patients to a general
      practitioner at an acute care post: an observational study.
AB  - OBJECTIVE: To assess the safety and efficiency of triaging low urgent self
      referred patients at the emergency department (ED) to a general practitioner (GP)
      based on the Manchester triage system (MTS). METHODS: All self-referred patients
      in the evening, night and weekends were included in this prospective
      observational study. Patients were triaged by an ED nurse according to the MTS
      and allocated to a GP or the ED according to a predefined care scheme. For
      patients treated by the GP, assessments were made of safety as measured by
      hospitalisation and return to the ED within 2 weeks, and efficiency as measured
      by referral to the ED. RESULTS: In 80% of cases allocation of the self-referrals
      to the ED or GP was according to a predefined scheme. Of the 3129 low urgent self
      referred patients triaged to the GP, 2840 (90.8%) were sent home, 202 (6.5%) were
      directly referred to the ED, 36 (1.2%) were hospitalised. Within a random sample
      of low urgent patients sent home by the GP (222 of 2840), 8 (3.6%) returned to
      the ED within 2 weeks. Against the agreed MTS scheme, the ED also directly
      treated 664 low urgent patients, mainly for extremity problems (n=512). Despite
      the care agreements, 227 urgent patients were treated by the GP, with a referral
      rate to the ED of 18.1%, a hospitalisation rate of 4.0% and a 4.5% return rate to
      the ED within 2 weeks. CONCLUSIONS: Low urgent self-referrals, with the exception
      of extremity problems, were shown to be treated efficiently and safely by a GP. A
      selected group of more urgent patients also seem to be handled adequately by the
      GP. Triage of low urgent patients with extremity problems and reasons for nurses
      not following a predefined triage allocation scheme need further elaboration.

PMID- 22158536
TI  - Knowledge, attitude and response of mothers about fever in their children.
AB  - AIM: This study was conducted to determine mothers' knowledge about fever, and
      their attitudes and responses to fever in children, along with the influence of
      demographic characteristics on the level of knowledge, and to identify
      occurrences of fear of fever. MATERIALS AND METHODS: The study consisted of 4500
      mothers with children 0-12 years of age who were referred to the pediatric health
      and disease polyclinic and primary care polyclinic over a period of 24 months.
      Data were collected using a questionnaire containing 32 open-ended, multichoice
      questions, and assessed using number, percentage and chi(2) analyses. RESULTS: In
      this study, 36% of mothers regarded body temperatures lower than 37 degrees C as
      fever; 83% believed that fever was harmful for their children, and 92.3%
      experienced fear and concern due to their child's fever. The most significant
      reason for fear was the belief that the child may have a seizure. Moreover, 12%
      of mothers feared that their child would die due to fever. The level of fear
      triggered by fever was lower as the education level of the mothers increased.
      Meanwhile, when their child had a fever, 28.9% of mothers used antifebrile drugs
      without consulting a physician, while 19% applied cold water and 7.7% applied
      water with alcohol or vinegar, among other inappropriate practices. CONCLUSION:
      Increased information about fevers geared towards the caregivers of children,
      particularly mothers, would prevent the unnecessary treatment of children, as
      well as minimising delayed and insufficient responses to fever.

PMID- 22158538
TI  - Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often
      progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We
      used whole-genome sequencing to perform an unbiased comprehensive screen to
      discover the somatic mutations in a sample from an individual with sAML and
      genotyped the loci containing these mutations in the matched MDS sample. Here we
      show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1
      was recurrently present in 13 out of 150 (8.7%) subjects with de novo MDS, and we
      found suggestive evidence of an increased risk of progression to sAML associated
      with this mutation. U2AF1 is a U2 auxiliary factor protein that recognizes the AG
      splice acceptor dinucleotide at the 3' end of introns, and the alterations in
      U2AF1 are located in highly conserved zinc fingers of this protein. Mutant U2AF1
      promotes enhanced splicing and exon skipping in reporter assays in vitro. This
      previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA
      splicing as a potential mechanism for MDS pathogenesis.

PMID- 22158539
TI  - Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre
      syndrome.
AB  - Myhre syndrome (MIM 139210) is a developmental disorder characterized by short
      stature, short hands and feet, facial dysmorphism, muscular hypertrophy, deafness
      and cognitive delay. Using exome sequencing of individuals with Myhre syndrome,
      we identified SMAD4 as a candidate gene that contributes to this syndrome on the
      basis of its pivotal role in the bone morphogenetic pathway (BMP) and
      transforming growth factor (TGF)-beta signaling. We identified three distinct
      heterozygous missense SMAD4 mutations affecting the codon for Ile500 in 11
      individuals with Myhre syndrome. All three mutations are located in the region of
      SMAD4 encoding the Mad homology 2 (MH2) domain near the site of
      monoubiquitination at Lys519, and we found a defect in SMAD4 ubiquitination in
      fibroblasts from affected individuals. We also observed decreased expression of
      downstream TGF-beta target genes, supporting the idea of impaired TGF-beta
      mediated transcriptional control in individuals with Myhre syndrome.

PMID- 22158537
TI  - Meta-analysis of genome-wide association studies identifies eight new loci for
      type 2 diabetes in east Asians.
AB  - We conducted a three-stage genetic study to identify susceptibility loci for type
      2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis
      of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865
      controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574
      controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172
      controls). The combined analysis identified eight new T2D loci reaching genome
      wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A,
      KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic
      beta cell development and insulin gene expression, is known for its association
      with fasting glucose levels. The evidence of an association with T2D for PEPD and
      HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent
      insulin secretion in the pancreas. These findings, derived from an east Asian
      population, provide new perspectives on the etiology of T2D.

PMID- 22158540
TI  - Genome-wide association study identifies five loci associated with susceptibility
      to pancreatic cancer in Chinese populations.
AB  - Pancreatic cancer has the lowest survival rate among human cancers, and there are
      no effective markers for its screening and early diagnosis. To identify genetic
      susceptibility markers for this cancer, we carried out a genome-wide association
      study on 981 individuals with pancreatic cancer (cases) and 1,991 cancer-free
      controls of Chinese descent using 666,141 autosomal SNPs. Promising associations
      were replicated in an additional 2,603 pancreatic cancer cases and 2,877 controls
      recruited from 25 hospitals in 16 provinces or cities in China. We identified
      five new susceptibility loci at chromosomes 21q21.3, 5p13.1, 21q22.3, 22q13.32
      and 10q26.11 (P = 2.24 * 10(-13) to P = 4.18 * 10(-10)) in addition to 13q22.1
      previously reported in populations of European ancestry. These results advance
      our understanding of the development of pancreatic cancer and highlight potential
      targets for the prevention or treatment of this cancer.

PMID- 22158541
TI  - Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene
      in chronic lymphocytic leukemia.
AB  - Here we perform whole-exome sequencing of samples from 105 individuals with
      chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in
      Western countries. We found 1,246 somatic mutations potentially affecting gene
      function and identified 78 genes with predicted functional alterations in more
      than one tumor sample. Among these genes, SF3B1, encoding a subunit of the
      spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated
      in 9.7% of affected individuals. Further analysis in 279 individuals with CLL
      showed that SF3B1 mutations were associated with faster disease progression and
      poor overall survival. This work provides the first comprehensive catalog of
      somatic mutations in CLL with relevant clinical correlates and defines a large
      set of new genes that may drive the development of this common form of leukemia.
      The results reinforce the idea that targeting several well-known genetic
      pathways, including mRNA splicing, could be useful in the treatment of CLL and
      other malignancies.

PMID- 22158542
TI  - GATA6 haploinsufficiency causes pancreatic agenesis in humans.
AB  - Understanding the regulation of pancreatic development is key for efforts to
      develop new regenerative therapeutic approaches for diabetes. Rare mutations in
      PDX1 and PTF1A can cause pancreatic agenesis, however, most instances of this
      disorder are of unknown origin. We report de novo heterozygous inactivating
      mutations in GATA6 in 15/27 (56%) individuals with pancreatic agenesis. These
      findings define the most common cause of human pancreatic agenesis and establish
      a key role for the transcription factor GATA6 in human pancreatic development.

PMID- 22158543
TI  - Desoxypipradrol is more potent than cocaine on evoked dopamine efflux in the
      nucleus accumbens.
AB  - Desoxypipradrol is a methylphenidate-like drug that has been recently found in a
      number of 'legal highs'. Evidence from emergency room toxicology reports suggests
      that this drug might have led to a number of psychotic events in drug abusers in
      the UK and elsewhere. However, very little research has been done on the effects
      of this drug on the brain. Here we used rat brain slices from the nucleus
      accumbens core, which were exposed to either cocaine (1, 3 or 10 uM) or
      desoxypipradrol (1, 3 or 10 uM) for 60 min. Dopamine efflux was electrically
      evoked and recorded using fast cyclic voltammetry. Both drugs increased the peak
      dopamine efflux and also slowed dopamine re-uptake. Desoxypipradrol was more
      potent than cocaine causing a sevenfold increase in peak dopamine levels (versus
      a threefold increase for cocaine) and increasing dopamine re-uptake half-life 15
      fold (versus fivefold for cocaine). These data suggest that desoxypipradrol is
      more potent than cocaine at dopamine terminals, and this could account for its
      psychotogenic effects.

PMID- 22158545
TI  - Commentary on 'Risk of incident diabetes with intensive-dose compared with
      moderate-dose statin therapy: a meta-analysis' by Preiss et al.

PMID- 22158544
TI  - Boosting serotonin in the brain: is it time to revamp the treatment of
      depression?
AB  - Abnormalities in serotonin systems are presumably linked to various psychiatric
      disorders including schizophrenia and depression. Medications intended for these
      disorders aim to either block the reuptake or the degradation of this
      neurotransmitter. In an alternative approach, efforts have been made to enhance
      serotonin levels through dietary manipulation of precursor levels with modest
      clinical success. In the last 30 years, there has been little improvement in the
      pharmaceutical management of depression, and now is the time to revisit
      therapeutic strategies for the treatment of this disease. Tryptophan hydroxylase
      (TPH) catalyzes the first and rate-limiting step in the biosynthesis of
      serotonin. A recently discovered isoform, TPH2, is responsible for serotonin
      biosynthesis in the brain. Learning how to activate this enzyme (and its
      polymorphic versions) may lead to a new, more selective generation of
      antidepressants, able to regulate the levels of serotonin in the brain with fewer
      side effects.

PMID- 22158547
TI  - Lack of EVER2 protein in two epidermodysplasia verruciformis patients with skin
      cancer presenting previously unreported homozygous genetic deletions in the EVER2
      gene.

PMID- 22158548
TI  - Regulatory T cells: banned cells for decades.
AB  - Regulatory T cells (Tregs), either thymic derived or peripherally induced,
      suppress a variety of physiological and pathological immune responses, and the
      absence of this cell subset has been shown to result in severe systemic
      autoimmunity. Since their acceptance almost two decades ago, intensive research
      aiming to characterize the phenotype, to elucidate the suppressive activity, and
      to decipher the migratory behavior of Tregs has been performed. A substantial
      number of studies, however, focused on understanding whether defects in Treg
      numbers and function contribute to the development and progression of
      inflammatory, autoimmune, and malignant disorders, and how Treg numbers/function
      might be modulated to treat patients with autoimmune diseases or cancer. In the
      skin, an organ that is constantly exposed to the environment, Tregs are known to
      be critically involved not only in the maintenance of skin homeostasis but also
      in the regulation of cutaneous immune responses. In this review, we present an
      overview on recent data concerning Treg development and expansion, the molecular
      mechanisms underlying their immunosuppressive activity, and the modulation of
      Treg function. Furthermore, we discuss the role of Tregs in cutaneous
      inflammatory and autoimmune disorders.

PMID- 22158549
TI  - Melanocytes: a window into the nervous system.
AB  - Melanocytes are pigment-producing cells that originate from the dorsal portions
      of the closing neural tube in vertebrate embryos. Similar to neurons, they are
      derived from pluripotent neural crest cells that differentiate into numerous cell
      lineages. The development of melanocytes and neurons, as well as their
      differentiated function, within the mature tissue, is influenced by signaling
      molecules produced by neighboring cells. The same signaling molecules that have a
      role in the central and peripheral nervous tissue also have a role in cutaneous
      melanocytes. These include Wnt, bone morphogenetic proteins, endothelins, steel
      factor, hepatocyte growth factor, fibroblast growth factors, and neurotrophins.
      Signaling pathways including PKC- and p53/p73-dependent pathways are also common
      to melanocytes and neurons. The similarity between melanocytes and neurons
      suggests that melanocytes could provide a valuable model for studies of diseases
      that affect the nervous system, as well as for development of potential therapies
      for these diseases.

PMID- 22158550
TI  - Metabolic inhibition of galectin-1-binding carbohydrates accentuates antitumor
      immunity.
AB  - Galectin-1 (Gal-1) has been shown to play a major role in tumor immune escape by
      inducing apoptosis of effector leukocytes and correlating with tumor
      aggressiveness and disease progression. Thus, targeting the Gal-1/Gal-1 ligand
      axis represents a promising cancer therapeutic approach. Here, to test the Gal-1
      mediated tumor immune evasion hypothesis and demonstrate the importance of Gal-1
      binding N-acetyllactosamines in controlling the fate and function of antitumor
      immune cells, we treated melanoma- or lymphoma-bearing mice with peracetylated 4
      fluoro-glucosamine (4-F-GlcNAc), a metabolic inhibitor of N-acetyllactosamine
      biosynthesis, and analyzed tumor growth and immune profiles. We found that 4-F
      GlcNAc spared Gal-1-mediated apoptosis of T cells and natural killer (NK) cells
      by decreasing their expression of Gal-1-binding determinants. 4-F-GlcNAc enhanced
      tumor lymphocytic infiltration and promoted elevations in tumor-specific
      cytotoxic T cells and IFN-gamma levels, while lowering IL-10 production.
      Collectively, our data suggest that metabolic lowering of Gal-1-binding N
      acetyllactosamines may attenuate tumor growth by boosting antitumor immune cell
      levels, representing a promising approach for cancer immunotherapy.

PMID- 22158551
TI  - How epidemiology has contributed to a better understanding of skin disease.
AB  - Epidemiology literally means "the study of what is upon the people." It puts the
      individual's condition in a population context and is the path to disease
      prevention. In the first part of this review, important aspects of epidemiology
      are discussed. Fundamentals of epidemiologic research include the measurement of
      occurrence of an event (prevalence and incidence) and the identification of
      factors that are associated with this event. The main study designs in
      observational studies are cohort, case-control, and cross-sectional studies, all
      of which have intrinsic strengths and limitations. These limitations include a
      variety of biases, which can be regrouped into selection bias, information bias,
      and confounding. The STROBE (Strengthening the Reporting of Observational Studies
      in Epidemiology) checklist is an important tool to further improve the reporting
      and quality of epidemiologic studies, and it is introduced. In the second part of
      this review, practical examples are presented, illustrating how
      dermatoepidemiology has contributed to an improved understanding of skin diseases
      and patient care, specifically in the case of melanoma therapy, serious cutaneous
      adverse reactions, Lyme disease, long-term safety of psoralin plus UVA (PUVA),
      teratogenicity of isotretinoin, and comorbidities in psoriasis.

PMID- 22158552
TI  - Innate immunity: ignored for decades, but not forgotten.
AB  - The innate immune system must recognize and rapidly respond to microbial
      pathogens, providing a first line of host defense. This is accomplished through
      an array of pattern recognition receptors (PRRs) that reside in specific
      subcellular compartments and can bind pathogen-associated molecular patterns.
      PRRs also recognize self-molecules that are released after cell damage or death,
      known as danger-associated molecular patterns, which can be actively transported
      across cell membranes. The activation of PRRs leads to host defense pathways in
      infectious diseases, but can also contribute to tissue injury in autoimmune
      diseases. The identification of these pathways has provided new insight into
      mechanisms of vaccination and holds promise for developing better vaccines.
      Finally, the identification of PRRs, their ligands, and signaling pathways
      provides an opportunity for developing new immunotherapeutic approaches to skin
      conditions in which activation of the innate immune response contributes to
      disease pathogenesis.

PMID- 22158553
TI  - Novel molecular therapies for heritable skin disorders.
AB  - Tremendous progress has been made in the past two decades in molecular genetics
      of heritable skin diseases, and pathogenic mutations have been identified in as
      many as 500 distinct human genes. This progress has resulted in improved
      diagnosis with prognostic implications, has refined genetic counseling, and has
      formed the basis for prenatal and presymptomatic testing and preimplantation
      genetic diagnosis. However, there has been relatively little progress in
      developing effective and specific treatments for these often devastating
      diseases. However, very recently, a number of novel molecular strategies,
      including gene therapy, cell-based approaches, and protein replacement therapy,
      have been explored for the treatment of these conditions. This overview will
      focus on the prototypic heritable blistering disorders, epidermolysis bullosa,
      and related keratinopathies, in which significant progress has been made recently
      toward treatment, and it will illustrate how some of the translational research
      therapies have already entered the clinical arena.

PMID- 22158555
TI  - Effect of personalization and candy incentive on response rates for a mailed
      survey of dermatologists.

PMID- 22158554
TI  - One remarkable molecule: filaggrin.
AB  - The discovery, in 2006, that loss-of-function mutations in the filaggrin (FLG)
      gene are the cause of ichthyosis vulgaris-the most common disorder of
      keratinization-and also a strong genetic risk factor for atopic eczema, marked a
      significant breakthrough in the understanding of eczema pathogenesis. Subsequent
      investigations of the role of FLG-null mutations have identified a series of
      significant associations with atopic disease phenotypes, including atopic asthma,
      allergic rhinitis, and peanut allergy. However, many questions remain to be
      answered in relation to the precise mechanisms by which deficiency of an
      intracellular protein expressed primarily in the differentiating epidermis may
      contribute to the development of cutaneous and systemic pathology. This review
      aims to highlight the key milestones in filaggrin research over the past 25
      years, to discuss the mechanistic, clinical, and therapeutic implications, and to
      consider possible future directions for ongoing investigation.

PMID- 22158556
TI  - Decrease of ceramides with very long-chain fatty acids and downregulation of
      elongases in a murine atopic dermatitis model.

PMID- 22158558
TI  - Purinergic signaling in healthy and diseased skin.
AB  - Adenosine 5'-triphosphate and adenosine receptors have been identified in adult
      and fetal keratinocytes, fibroblasts, melanocytes, mast cells, Langerhans cells,
      and Meissner's corpuscles, as well as in hair follicles, sweat glands, and smooth
      muscle and endothelial cells of skin vessels. Purinergic signaling is involved in
      skin pathology, including inflammation, wound healing, pain, psoriasis,
      scleroderma, warts, and skin cancer.

PMID- 22158557
TI  - Host phenotype characteristics and MC1R in relation to early-onset basal cell
      carcinoma.
AB  - Basal cell carcinoma (BCC) incidence is increasing, particularly among adults
      under the age of 40 years. Pigment-related characteristics are associated with
      BCC in older populations, but epidemiologic studies among younger individuals and
      analyses of phenotype-genotype interactions are limited. We examined self
      reported phenotypes and melanocortin 1 receptor gene (MC1R) variants in relation
      to early-onset BCC. BCC cases (n=377) and controls with benign skin conditions
      (n=390) under the age of 40 years were identified through Yale's Dermatopathology
      database. Factors most strongly associated with early-onset BCC were skin
      reaction to first summer sun for 1 hour (severe sunburn vs. tan odds ratio
      (OR)=12.27, 95% confidence interval (CI)=4.08-36.94) and skin color (very fair
      vs. olive OR=11.06, 95% CI=5.90-20.74). Individuals with two or more MC1R non
      synonymous variants were 3.59 times (95% CI=2.37-5.43) more likely to have BCC
      than those without non-synonymous variants. All host characteristics and MC1R
      were more strongly associated with multiple BCC case status (37% of cases) than a
      single BCC case status. MC1R, number of moles, skin reaction to first summer sun
      for 1 hour, and hair and skin color were independently associated with BCC. BCC
      risk conferred by MC1R tended to be stronger among those with darker pigment
      phenotypes, traditionally considered to be at low risk of skin cancer.

PMID- 22158559
TI  - Cutaneous lymphomas: molecular pathways leading to new drugs.
AB  - Currently, cutaneous lymphomas represent a paradigm for the heterogeneity and the
      dynamic variability of neoplastic disorders resulting in the accumulation of
      clonal lymphocytes in the skin, and thus mirror the complexity of lymphocytic
      populations. Increasing knowledge and insight in pathobiology offer new
      opportunities for targeted interventions to selectively hit the tumor
      populations. mAbs, rexinoids, small kinase inhibitors, or molecules interfering
      with methylation or histone acetylation contribute to disease control. The
      rational and well-coordinated application of these tools, together with improved
      chemotherapeutic options, will hopefully further improve treatment success in the
      near future.

PMID- 22158560
TI  - Antimicrobial peptides: old molecules with new ideas.
AB  - Almost 90 years have passed since Alexander Fleming discovered the antimicrobial
      activity of lysozyme, the first natural antibiotic isolated from our body. Since
      then, various types of molecules with antibiotic activity have been isolated from
      animals, insects, plants, and bacteria, and their use has revolutionized clinical
      medicine. So far, more than 1,200 types of peptides with antimicrobial activity
      have been isolated from various cells and tissues, and it appears that all living
      organisms use these antimicrobial peptides (AMPs) in their host defense. In the
      past decade, innate AMPs produced by mammals have been shown to be essential for
      the protection of skin and other organs. Their importance is because of their
      pleiotrophic functions to not only kill microbes but also control host
      physiological functions such as inflammation, angiogenesis, and wound healing.
      Recent advances in our understanding of the function of AMPs have associated
      their altered production with various human diseases such as psoriasis, atopic
      dermatitis, and rosacea. In this review, we summarize the history of AMP biology
      and provide an overview of recent research progress in this field.

PMID- 22158561
TI  - Psoriasis and other complex trait dermatoses: from Loci to functional pathways.
AB  - Driven by advances in molecular genetic technologies and statistical analysis
      methodologies, there have been huge strides taken in dissecting the complex
      genetic basis of many inflammatory dermatoses. One example is psoriasis, for
      which application of classical linkage analysis and genome-wide association
      investigation has identified genetic loci of major and minor effect. Although
      most loci independently have modest genetic effects, they identify important
      biological pathways potentially relevant to disease pathogenesis and therapeutic
      intervention. In the case of psoriasis, these appear to involve the epidermal
      barrier, NF-kappaB mechanisms, and T helper type 17 adaptive immune responses.
      The advent of next-generation sequencing methods will permit a more detailed and
      complete map of disease genetic architecture, a key step in developing
      personalized medicine strategies in the clinical management of the complex
      inflammatory dermatoses.

PMID- 22158562
TI  - Unveiling the burden of influenza-associated pneumococcal pneumonia.

PMID- 22158563
TI  - Anthrax lethal and edema toxins fail to directly impair human platelet function.
AB  - Hemorrhage is a prominent clinical manifestation of systemic anthrax. Therefore,
      we have examined the effects of anthrax lethal and edema toxins on human
      platelets. We find that anthrax lethal toxin fails to cleave its target, mitogen
      activated protein kinase 1, and anthrax edema toxin fails to increase
      intracellular cyclic adenosine monophosphate. Surface expression of toxin
      receptors tumor endothelial marker 8 and capillary morphogenesis gene 2, as well
      as coreceptor low density lipoprotein receptor-related protein 6 (LRP6), are
      markedly reduced, preventing toxin binding to platelets. Our studies suggest that
      the hemorrhagic clinical manifestations of systemic anthrax are unlikely to be
      caused by the direct binding and entry of anthrax toxins into human platelets.

PMID- 22158564
TI  - Impact of the 2009 influenza pandemic on pneumococcal pneumonia hospitalizations
      in the United States.
AB  - BACKGROUND: Infection with influenza virus increases the risk for developing
      pneumococcal disease. The A/H1N1 influenza pandemic in autumn 2009 provided a
      unique opportunity to evaluate this relationship. METHODS: Using weekly age-,
      state-, and cause-specific hospitalizations from the US State Inpatient Databases
      of the Healthcare Cost and Utilization Project 2003-2009, we quantified the
      increase in pneumococcal pneumonia hospitalization rates above a seasonal
      baseline during the pandemic period. RESULTS: We found a significant increase in
      pneumococcal hospitalizations from late August to mid-December 2009, which
      corresponded to the timing of highest pandemic influenza activity. Individuals
      aged 5-19 years, who have a low baseline level of pneumococcal disease,
      experienced the largest relative increase in pneumococcal hospitalizations
      (ratio, 1.6 [95% confidence interval {CI}, 1.4-1.7]), whereas the largest
      absolute increase was observed among individuals aged 40-64 years. In contrast,
      there was no excess disease in the elderly. Geographical variation in the timing
      of excess pneumococcal hospitalizations matched geographical patterns for the
      fall pandemic influenza wave. CONCLUSIONS: The 2009 influenza pandemic had a
      significant impact on the rate of pneumococcal pneumonia hospitalizations, with
      the magnitude of this effect varying between age groups and states, mirroring
      observed variations in influenza activity.

PMID- 22158565
TI  - Hyporesponsiveness following booster immunization with bacterial polysaccharides
      is caused by apoptosis of memory B cells.
AB  - BACKGROUND: Repeated immunizations with polysaccharide (PS) vaccines cause
      hyporesponsiveness through undefined mechanisms. We assessed the effects of a PS
      booster on immune responses, frequency, and survival of PS-specific B-cell
      subpopulations in spleen and bone marrow. METHODS: Neonatal mice were primed with
      meningococcus serotype C (MenC) conjugate MenC-CRM(197)+CpG1826, boosted with
      MenC-CRM(197), MenC-PS, or saline; subsequently, bromodeoxyuridine (BrdU) was
      injected daily intraperitoneally. MenC-PS-specific cells were labeled with
      fluorescent MenC-PS and phenotyped by flow cytometry. RESULTS: After MenC-PS
      booster, proliferating (BrdU(+)) MenC-PS-specific naive B cells (CD138(
      )/B220(+); P = .0003) and plasma cells (CD138(+)/B220(-); P = .0002) in spleen
      were fewer than after saline booster. BrdU(+) MenC-PS-specific plasma cells were
      also reduced in bone marrow (P = .0308). Compared to saline, MenC-PS booster
      reduced BrdU(+) IgG(+) MenC-PS-specific B cells in spleen (P = .0002). Twelve
      hours after the MenC-PS booster, an increased frequency of apoptotic
      (AnnexinV(+)) MenC-PS-specific B cells in spleen was observed compared with MenC
      CRM(197) (P = .0286) or saline (P = .001) boosters. CONCLUSIONS: We demonstrated
      that the MenC-PS booster significantly reduced the frequency of newly activated
      MenC-PS-specific B cells-mostly switched IgG(+) memory cells-by driving them into
      apoptosis. It shows directly that apoptosis of PS-specific memory cells is the
      cause of PS-induced hyporesponsiveness. These results should be taken into
      account prior to consideration of the use of PS vaccines.

PMID- 22158566
TI  - RGS2-mediated intracellular Ca2+ level plays a key role in the intracellular
      replication of Brucella abortus within phagocytes.
AB  - BACKGROUND: Brucella abortus can proliferate within professional and
      nonprofessional phagocytic host cells and thereby successfully bypass the
      bacteriocidal effects of phagocytes. However, the intracellular survival
      mechanism and factors of virulence are not fully understood. METHODS: We have
      investigated the role of the regulator of G protein signaling 2 (RGS2), an
      intracellular calcium ([Ca(2+)](i)) regulator of the host cell, in the
      intracellular survival of B. abortus within phagocytes. RESULTS: B. abortus
      infection markedly induced RGS2 messenger RNA expression in early phase and
      increased the [Ca(2+)](i) level up to 24 hours postinfection within macrophages
      from wild-type mice. The [Ca(2+)](i) level, however, was not influenced by B.
      abortus infection within macrophages from RGS2-deficient mice. Furthermore, B.
      abortus survival was reduced within RGS2-deficient macrophages, and hence
      bacterial proliferation was inhibited in RGS2-deficient mice. Moreover, treatment
      with the Ca(2+) chelator ethylenediaminetetraacetic acid (EDTA) or 1,2-bis-(2
      amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM)
      and the L-type Ca(2+) channel-blocking agent nifedipine or genistein also showed
      a reduced intracellular replication of B. abortus within macrophages. CONCLUSION:
      These results indicate that B. abortus infection induces host RGS2 expression and
      that up-regulation of [Ca(2+)](i) levels is an essential factor for the
      intracellular survival of B. abortus within phagocytes.

PMID- 22158568
TI  - Denosumab for the treatment of osteoporosis and cancer-related conditions.
AB  - Osteoporotic fractures and adverse skeletal effects of malignancies are
      associated with high bone turnover. Denosumab is a potent inhibitor of bone
      resorption with a novel mechanism of action. It is administered as an infrequent
      subcutaneous injection with no restrictions relating to renal function. This
      review summarizes data on the efficacy and safety of denosumab that led to its
      approval for the treatment of postmenopausal osteoporosis, cancer treatment
      induced bone loss, and skeletal complications of malignancies.

PMID- 22158567
TI  - Prevention of antibiotic-nonsusceptible Streptococcus pneumoniae with conjugate
      vaccines.
AB  - BACKGROUND: Streptococcus pneumoniae (pneumococcus) caused approximately 44000 US
      invasive pneumococcal disease (IPD) cases in 2008. Antibiotic nonsusceptibility
      complicates IPD treatment. Using penicillin susceptibility breakpoints adopted in
      2008, we evaluated antibiotic-nonsusceptible IPD trends in light of the
      introductions of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 and a
      13-valent pneumococcal conjugate vaccine (PCV13) in 2010. METHODS: IPD cases were
      defined by isolation of pneumococcus from a normally sterile site in individuals
      residing in Active Bacterial Core surveillance (ABCs) areas during 1998-2008.
      Pneumococci were serotyped and tested for antibiotic susceptibility using broth
      microdilution. RESULTS: During 1998-2008, ABCs identified 43198 IPD cases.
      Penicillin-nonsusceptible strains caused 6%-14% of IPD cases, depending on age.
      Between 1998-1999 and 2008, penicillin-nonsusceptible IPD rates declined 64% for
      children aged <5 years (12.1-4.4 cases per 100000), and 45% for adults aged >=65
      (4.8-2.6 cases per 100000). Rates of IPD nonsusceptible to multiple antibiotics
      mirrored these trends. During 2007-2008, serotypes in PCV13 but not PCV7 caused
      78%-97% of penicillin-nonsusceptible IPD, depending on age. CONCLUSIONS:
      Antibiotic-nonsusceptible IPD rates remain below pre-PCV7 rates for children <5
      and adults >=65 years old. PCV13 vaccines hold promise for further
      nonsusceptibility reductions.

PMID- 22158569
TI  - Vandetanib for the treatment of thyroid cancer.
AB  - Vandetanib is a small-molecule inhibitor of vascular endothelial growth factor
      receptor (VEGFR), epidermal growth factor receptor (EGFR), and RET tyrosine
      kinases that has demonstrated clinical benefits in patients with medullary
      thyroid cancer (MTC). By identifying patients who are in greatest need of
      therapy, the risks of vandetanib can be balanced against the potential benefits
      in patients for whom there had been no effective therapy until now. This review
      discusses the development of vandetanib in patients with MTC and the benefits and
      risks in this patient population.

PMID- 22158570
TI  - The irregular tachycardia that was not atrial fibrillation.

PMID- 22158573
TI  - Prevalence of cancer screening in older, racially diverse adults: still screening
      after all these years.
AB  - BACKGROUND: While a great deal is known about cancer screening behaviors and
      trends in young and middle-aged adults, little is known about screening behaviors
      in older adults from different racial backgrounds. Our goal was to establish
      prevalence estimates and correlates of cancer screening, including physician
      recommendation in older (>=75 years), racially diverse adults. METHODS: Data were
      analyzed from the National Health Interview Survey--an annual, in-person,
      nationwide survey used to track health trends in US civilians. The analytic
      sample included 49,575 individuals, of whom 1697 were 75 to 79 years old and 2376
      were 80 years or older. Screening behaviors were examined according to the US
      Preventive Services Task Force recommendations for breast, cervical, colorectal,
      and prostate cancer screening. RESULTS: Among adults aged 75 to 79 years, the
      percentage screened for cancer was as follows: colorectal, 57%; breast, 62%;
      cervical, 53%; and prostate, 56%. Among those 80 years or older, rates of
      screening ranged from a low of 38% for cervical cancer to a high of 50% for
      breast cancer. Although unadjusted screening prevalence rates differed by
      race/ethnicity, these differences were accounted for by low education attainment
      in the multivariate logistic regression model. Physician recommendation for a
      specific test was the largest predictor of screening. Over 50% of men and women
      older than 75 years report that their physicians continue to recommend screening.
      CONCLUSION: A high percentage of older adults continue to be screened in the face
      of ambiguity of recommendations for this group.

PMID- 22158574
TI  - What is the right cancer screening rate for older adults.

PMID- 22158575
TI  - Coronary artery calcium scanning in primary prevention: a conversation with
      cardiology fellows.

PMID- 22158576
TI  - The pelvic examination as a screening tool: practices of US physicians.

PMID- 22158577
TI  - Pelvic examinations in asymptomatic women: tipping a sacred cow.

PMID- 22158578
TI  - Prehospital cardiac markers in defining ambiguous chest pain.

PMID- 22158579
TI  - Effect of integrated care on advanced chronic obstructive pulmonary disease in
      high-mortality rural areas.

PMID- 22158580
TI  - The role of gender in examination and counseling for melanoma in primary care.

PMID- 22158581
TI  - Reanalysis of NHANES III data on sodium association with mortality: appropriate
      adjustment for potassium not performed.

PMID- 22158582
TI  - Method of estimating sodium intake and its possible influence on NHANES III
      outcome.

PMID- 22158583
TI  - A defense of early renal referral: preventing progression to end-stage renal
      disease.

PMID- 22158584
TI  - Early nephrology referral: how early is early enough?

PMID- 22158585
TI  - Predialysis nephrology care of older patients approaching end-stage renal
      disease.

PMID- 22158586
TI  - Impact of nephrologic care in the early management of chronic kidney disease.

PMID- 22158588
TI  - Chronic pelvic pain: finding the cure.

PMID- 22158587
TI  - Soy isoflavone supplementation in menopausal women.

PMID- 22158589
TI  - 'Heat-treatment aqueous two phase system' for purification of serine protease
      from Kesinai (Streblus asper) leaves.
AB  - A 'Heat treatment aqueous two phase system' was employed for the first time to
      purify serine protease from kesinai (Streblus asper) leaves. In this study,
      introduction of heat treatment procedure in serine protease purification was
      investigated. In addition, the effects of different molecular weights of
      polyethylene glycol (PEG 4000, 6000 and 8000) at concentrations of 8, 16 and 21%
      (w/w) as well as salts (Na-citrate, MgSO4 and K2HPO4) at concentrations of 12,
      15, 18% (w/w) on serine protease partition behavior were studied. Optimum
      conditions for serine protease purification were achieved in the PEG-rich phase
      with composition of 16% PEG6000-15% MgSO4. Also, thermal treatment of kesinai
      leaves at 55  degrees C for 15 min resulted in higher purity and recovery yield
      compared to the non-heat treatment sample. Furthermore, this study investigated
      the effects of various concentrations of NaCl addition (2, 4, 6 and 8% w/w) and
      different pH (4, 7 and 9) on the optimization of the system to obtain high yields
      of the enzyme. The recovery of serine protease was significantly enhanced in the
      presence of 4% (w/w) of NaCl at pH 7.0. Based on this system, the purification
      factor was increased 14.4 fold and achieved a high yield of 96.7%.

PMID- 22158590
TI  - Antioxidant, anti-glycation and anti-inflammatory activities of phenolic
      constituents from Cordia sinensis.
AB  - Nine compounds have been isolated from the ethyl acetate soluble fraction of C.
      sinensis, namely protocatechuic acid (1), trans-caffeic acid (2), methyl
      rosmarinate (3), rosmarinic acid (4), kaempferide-3-O-beta-D-glucopyranoside (5),
      kaempferol-3-O-beta-D-glucopyranoside (6), quercetin-3-O-beta-D-glucopyranoside
      (7), kaempferide-3-O-alpha-L-rhamnopyranosyl (1->6)-beta-D-glucopyranoside (8)
      and kaempferol-3-O-alpha-L-rhamno-pyranosyl (1->6)-beta-D-glucopyranoside (9),
      all reported for the first time from this species. The structures of these
      compounds were deduced on the basis of spectroscopic studies, including 1D and 2D
      NMR techniques. Compounds 1-9 were investigated for biological activity and
      showed significant anti-inflammatory activity in the carrageen induced rat paw
      edema test. The antioxidant activities of isolated compounds 1-9 were evaluated
      by the DPPH radical scavenging test, and compounds 1, 2, 4 and 7-9 exhibited
      marked scavenging activity compared to the standard BHA. These compounds were
      further studied for their anti-glycation properties and some compounds showed
      significant anti-glycation inhibitory activity. The purity of compounds 2-5, 8
      and 9 was confirmed by HPLC. The implications of these results for the
      chemotaxonomic studies of the genus Cordia have also been discussed.

PMID- 22158591
TI  - Discovery of potential M2 channel inhibitors based on the amantadine scaffold via
      virtual screening and pharmacophore modeling.
AB  - The M2 channel protein on the influenza A virus membrane has become the main
      target of the anti-flu drugs amantadine and rimantadine. The structure of the M2
      channel proteins of the H3N2 (PDB code 2RLF) and 2009-H1N1 (Genbank accession
      number GQ385383) viruses may help researchers to solve the drug-resistant problem
      of these two adamantane-based drugs and develop more powerful new drugs against
      influenza A virus. In the present study, we searched for new M2 channel
      inhibitors through a combination of different computational methodologies,
      including virtual screening with docking and pharmacophore modeling. Virtual
      screening was performed to calculate the free energies of binding between
      receptor M2 channel proteins and 200 new designed ligands. After that,
      pharmacophore analysis was used to identify the important M2  protein-inhibitor
      interactions and common features of top binding compounds with M2 channel
      proteins. Finally, the two most potential compounds were determined as novel
      leads to inhibit M2 channel proteins in both H3N2 and 2009-H1N1 influenza A
      virus.

PMID- 22158592
TI  - The photochemistry of benzotriazole derivatives. Part 2: photolysis of 1
      substituted benzotriazole arylhydrazones: new route to phenanthridin-6-yl-2
      phenyldiazines.
AB  - Irradiation of 1-substituted benzotriazole arylhydrazones 3a-c, 4a,b and 5a,b
      with a 16 W low pressure mercury arc-lamp (254 nm) for 24 h gave phenanthridin-6
      yl-2-phenyldiazines 9a-c, phenanthridin-6(5H)-ones 10a-c, 1-anilinobenzimidazoles
      11a-c,  2-aryl-1H-benzimidazoles 12a-c, 1-arylamino-1H-benzimidazol-2-carboxylic
      acid ethyl esters 14a,b, 1-aryl-1H, 9H-benzo [4,5][1,2,3] triazolo[1,2
      a]tetrazole-3-carboxylic acid ethyl esters 16a,b, 1-arylamino-2
      benzoylbenzimidazoles 18a,b and 2-benzoylbenzoxazole 21.

PMID- 22158593
TI  - Urinary tract obstruction: ureteral stents--weighing up the risks and benefits.

PMID- 22158594
TI  - Prostate cancer: ideal candidates for focal therapy.

PMID- 22158595
TI  - Health policy: lost in transition, losing money, but caution precludes a "quick
      fix".

PMID- 22158598
TI  - Kidney cancer in 2011: objectifying risk for localized renal masses.

PMID- 22158597
TI  - Molecular biomarkers in urothelial carcinoma of the bladder: are we there yet?
AB  - The unprecedented advances in cancer genetics and genomics are rapidly affecting
      the clinical management of solid tumors. Molecular diagnostics are now an
      integral part of routine clinical management for patients with lung, colon, and
      breast cancer. In sharp contrast, molecular biomarkers have been largely excluded
      from current management algorithms for urologic malignancies. The need for new
      treatment options that can improve upon the modest outcomes currently associated
      with muscle-invasive bladder cancer is evident, and validated prognostic
      molecular biomarkers that can help clinicians to identify patients in need of
      early, aggressive management are lacking. Robust predictive biomarkers that are
      able to forecast and stratify responses to emerging targeted therapies are also
      needed.

PMID- 22158596
TI  - Role of potassium ion channels in detrusor smooth muscle function and
      dysfunction.
AB  - Contraction and relaxation of the detrusor smooth muscle (DSM), which makes up
      the wall of the urinary bladder, facilitates the storage and voiding of urine.
      Several families of K(+) channels, including voltage-gated K(+) (K(V)) channels,
      Ca(2+)-activated K(+) (K(Ca)) channels, inward-rectifying ATP-sensitive K(+)
      (K(ir), K(ATP)) channels, and two-pore-domain K(+) (K(2P)) channels, are
      expressed and functional in DSM. They control DSM excitability and contractility
      by maintaining the resting membrane potential and shaping the action potentials
      that determine the phasic nature of contractility in this tissue. Defects in DSM
      K(+) channel proteins or in the molecules involved in their regulatory pathways
      may underlie certain forms of bladder dysfunction, such as overactive bladder.
      K(+) channels represent an opportunity for novel pharmacological manipulation and
      therapeutic intervention in human DSM. Modulation of DSM K(+) channels directly
      or indirectly by targeting their regulatory mechanisms has the potential to
      control urinary bladder function. This Review summarizes our current state of
      knowledge of the functional role of K(+) channels in DSM in health and disease,
      with special emphasis on current advancements in the field.

PMID- 22158599
TI  - Magic sized ZnS quantum dots as a highly sensitive and selective fluorescence
      sensor probe for Ag+ ions.
AB  - A green and simple chemical synthesis of magic sized water soluble blue-emitting
      ZnS quantum dots (QDs) has been accomplished by reacting anhydrous Zn acetate,
      sodium sulfide and thiolactic acid (TLA) at room temperature in aqueous solution.
      Refluxing of this mixture in open air yielded ZnS clusters of about 3.5 nm in
      diameter showing very strong and narrow photoluminescence properties with long
      stability. Refluxing did not cause any noticeable size increment of the clusters.
      As a result, the QDs obtained after different refluxing conditions showed similar
      absorption and photoluminescence (PL) features. Use of TLA as a capping agent
      effectively yielded such stable and magic sized QDs. The as-synthesized and 0.5 h
      refluxed ZnS QDs were used as a fluorescence sensor for Ag(+) ions. It has been
      observed that after addition of Ag(+) ions of concentration 0.5-1 MUM the strong
      fluorescence of ZnS QDs was almost quenched. The quenched fluorescence can be
      recovered by adding ethylenediamine to form a complex with Ag(+) ions. The other
      metal ions (K(+), Ca(2+), Au(3+), Cu(2+), Fe(3+), Mn(2+), Mg(2+), Co(2+)) showed
      little or no effect on the fluorescence of ZnS QDs when tested individually or as
      a mixture. In the presence of all these ions, Ag(+) responded well and therefore
      ZnS QDs reported in this work can be used as a Ag(+) ion fluorescence sensor.

PMID- 22158604
TI  - Reducing the incidence and severity of acute graft-versus-host disease.

PMID- 22158605
TI  - The AhR-Nrf2 pathway in keratinocytes: on the road to chemoprevention?
AB  - The ligand-activated transcription factor AhR mediates the cutaneous stress
      response toward a variety of environmental noxae and is therefore currently of
      interest for modern preventive medicine. In this issue, Tsuji et al. identify the
      antifungal agent ketoconazole as an inducer of AhR signaling and the Nrf2
      antioxidant response in human keratinocytes. Ketoconazole-stimulated nuclear
      translocation of Nrf2 and its cytoprotective effects against oxidative stress
      strongly depend on a functional AhR. This newly identified AhR-Nrf2 pathway opens
      up new opportunities to prevent and treat inflammatory skin diseases.

PMID- 22158606
TI  - Profilaggrin, dry skin, and atopic dermatitis risk: size matters.
AB  - Mutations in the FLG gene, which encodes profilaggrin, are known to be a major
      risk factor for atopic dermatitis as well as other atopic diseases and systemic
      allergies. New research, however, shows that intragenic copy number variation
      within FLG also represents an independent risk factor for atopic dermatitis. The
      new findings indicate that upregulating FLG protein levels by 5-10% may have
      clinical utility in improving the management of many patients with dry skin and
      atopy.

PMID- 22158607
TI  - Dermatology life quality index: time to move forward.
AB  - Since its introduction in 1994, the Dermatology Life Questionnaire Index (DLQI)
      has played an important role in assessing dermatology-specific health-related
      quality of life (HRQoL) and has affected several medical decision-making
      processes. However, the psychometric requirements for instruments have evolved
      over the years, and the DQLI is failing these new standards. Therefore, it is
      time to move forward and use valuable alternatives because the DLQI's scientific
      limitations outweigh the practicalities of its use.

PMID- 22158608
TI  - Targeting skin: vitiligo and autoimmunity.
AB  - In this issue, Singh and co-workers describe the results of classical typing of
      human leukocyte antigen (HLA) alleles in 1,404 vitiligo patients and 902
      unaffected controls from North India and follow-up HLA typing in 355 cases and
      441 controls from Gujarat. The increased frequency of DRB1*07:01 in North Indian
      and Gujarat populations with generalized and localized vitiligo and in several
      vitiligo populations studied previously suggests that it contributes to
      autoimmunity and destruction of melanocytes.

PMID- 22158609
TI  - Control of central and peripheral tolerance to melanocyte differentiation
      antigens by GILT.
AB  - The strict control of the T-cell receptor repertoire is essential for prevention
      of autoimmune diseases. The repertoire of T cells is primarily formed in the
      thymus through positive and negative selection. The risk of an incomplete removal
      of autoreactive T cells necessitates additional means to maintain peripheral
      tolerance. There is increasing evidence that the interferon (IFN)-gamma-inducible
      lysosomal thiol reductase (GILT) allows peripheral tolerance to a melanocyte
      differentiation antigen by induction of specific regulatory T cells.

PMID- 22158610
TI  - Expansion of maxillary arches with crossbite: a systematic review of RCTs in the
      last 12 years.
AB  - The aim of this study was to review recent randomized clinical trials (RCTs)
      dealing with the effectiveness of various modalities of orthopaedic/orthodontic
      expansion of maxillary arches with crossbite and the associated 6 month post
      retention stability. The study selection criteria included RCTs involving
      subjects with maxillary deficiency with crossbite, with no limits of age. The
      authors searched the following electronic databases from 1999 to January 2011:
      the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, LILACS,
      and WEB of SCIENCE. The search strategy resulted in 12 articles meeting the
      inclusion criteria. Most of the studies did not meet major methodological
      requirements; some studies were not relevant because of small sample size,
      possible bias and unaccounted for confounding variables, lack of blinding in
      measurements, and deficient statistical methods. Treatment outcomes were
      different depending on the appliance used, tooth tissue-borne/tooth-borne
      expanders, bonded semi-rapid maxillary expansion (SRME), or rapid maxillary
      expansion (RME); in any case, methodological flaws prevent any sound conclusion.
      Stable results have been measured at the 6 month follow-up after removal of the
      retention plate in the treated groups in the maxillary intermolar and intercanine
      distances. Long-term stability results should be assessed. The Consolidated
      Standards of Reporting Trials (CONSORT) Statement could be helpful in improving
      the reporting of RCTs.

PMID- 22158612
TI  - Regenerating islet-derived 1alpha (Reg-1alpha) protein is new neuronal secreted
      factor that stimulates neurite outgrowth via exostosin Tumor-like 3 (EXTL3)
      receptor.
AB  - Regenerating islet-derived 1alpha (Reg-1alpha)/lithostathine, a member of a
      family of secreted proteins containing a C-type lectin domain, is expressed in
      various organs and plays a role in proliferation, differentiation, inflammation,
      and carcinogenesis of cells of the digestive system. We previously reported that
      Reg-1alpha is overexpressed during the very early stages of Alzheimer disease,
      and Reg-1alpha deposits were detected in the brain of patients with Alzheimer
      disease. However, the physiological function of Reg-1alpha in neural cells
      remains unknown. Here, we show that Reg-1alpha is expressed in neuronal cell
      lines (PC12 and Neuro-2a) and in rat primary hippocampal neurons (E17.5). Reg
      1alpha is mainly localized around the nucleus and at the membrane of cell bodies
      and neurites. Transient overexpression of Reg-1alpha or addition of recombinant
      Reg-1alpha significantly increases the number of cells with longer neurites by
      stimulating neurite outgrowth. These effects are abolished upon down-regulation
      of Reg-1alpha by siRNA and following inhibition of secreted Reg-1alpha by
      antibodies. Moreover, Reg-1alpha colocalizes with exostosin tumor-like 3 (EXTL3),
      its putative receptor, at the membrane of these cells. Overexpression of EXTL3
      increases the effect of recombinant Reg-1alpha on neurite outgrowth, and Reg
      1alpha is not effective when EXTL3 overexpression is down-regulated by shRNA. Our
      findings indicate that Reg-1alpha regulates neurite outgrowth and suggest that
      this effect is mediated by its receptor EXTL3.

PMID- 22158613
TI  - Apoptosis-dependent externalization and involvement in apoptotic cell clearance
      of DmCaBP1, an endoplasmic reticulum protein of Drosophila.
AB  - To elucidate the actions of Draper, a receptor responsible for the phagocytic
      clearance of apoptotic cells in Drosophila, we isolated proteins that bind to the
      extracellular region of Draper using affinity chromatography. One of those
      proteins has been identified to be an uncharacterized protein called Drosophila
      melanogaster calcium-binding protein 1 (DmCaBP1). This protein containing the
      thioredoxin-like domain resided in the endoplasmic reticulum and seemed to be
      expressed ubiquitously throughout the development of Drosophila. DmCaBP1 was
      externalized without truncation after the induction of apoptosis somewhat prior
      to chromatin condensation and DNA cleavage in a manner dependent on the activity
      of caspases. A recombinant DmCaBP1 protein bound to both apoptotic cells and a
      hemocyte-derived cell line expressing Draper. Forced expression of DmCaBP1 at the
      cell surface made non-apoptotic cells susceptible to phagocytosis. Flies
      deficient in DmCaBP1 expression developed normally and showed Draper-mediated
      pruning of larval axons, but a defect in the phagocytosis of apoptotic cells in
      embryos was observed. Loss of Pretaporter, a previously identified ligand for
      Draper, did not cause a further decrease in the level of phagocytosis in DmCaBP1
      lacking embryos. These results collectively suggest that the endoplasmic
      reticulum protein DmCaBP1 is externalized upon the induction of apoptosis and
      serves as a tethering molecule to connect apoptotic cells and phagocytes for
      effective phagocytosis to occur.

PMID- 22158614
TI  - E74-like factor 3 (ELF3) impacts on matrix metalloproteinase 13 (MMP13)
      transcriptional control in articular chondrocytes under proinflammatory stress.
AB  - Matrix metalloproteinase (MMP)-13 has a pivotal, rate-limiting function in
      cartilage remodeling and degradation due to its specificity for cleaving type II
      collagen. The proximal MMP13 promoter contains evolutionarily conserved E26
      transformation-specific sequence binding sites that are closely flanked by AP-1
      and Runx2 binding motifs, and interplay among these and other factors has been
      implicated in regulation by stress and inflammatory signals. Here we report that
      ELF3 directly controls MMP13 promoter activity by targeting an E26 transformation
      specific sequence binding site at position -78 bp and by cooperating with AP-1.
      In addition, ELF3 binding to the proximal MMP13 promoter is enhanced by IL-1beta
      stimulation in chondrocytes, and the IL-1beta-induced MMP13 expression is
      inhibited in primary human chondrocytes by siRNA-ELF3 knockdown and in
      chondrocytes from Elf3(-/-) mice. Further, we found that MEK/ERK signaling
      enhances ELF3-driven MMP13 transactivation and is required for IL-1beta-induced
      ELF3 binding to the MMP13 promoter, as assessed by chromatin immunoprecipitation.
      Finally, we show that enhanced levels of ELF3 co-localize with MMP13 protein and
      activity in human osteoarthritic cartilage. These studies define a novel role for
      ELF3 as a procatabolic factor that may contribute to cartilage remodeling and
      degradation by regulating MMP13 gene transcription.

PMID- 22158615
TI  - Death receptors 4 and 5 activate Nox1 NADPH oxidase through riboflavin kinase to
      induce reactive oxygen species-mediated apoptotic cell death.
AB  - Stimulation of the proapoptotic tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL) receptors, death receptors 4 (DR4) and 5 (DR5),
      conventionally induces caspase-dependent apoptosis in tumor cells. Here we report
      that stimulation of DR4 and/or DR5 by the agonistic protein KD548-Fc, an Fc-fused
      DR4/DR5 dual-specific Kringle domain variant, activates plasma membrane
      associated Nox1 NADPH oxidase to generate superoxide anion and subsequently
      accumulates intracellular reactive oxygen species (ROS), leading to sustained c
      Jun N-terminal kinase activation and eventual apoptotic cell death in human HeLa
      and Jurkat tumor cells. KD548-Fc treatment induces the formation of a DR4/DR5
      signaling complex containing riboflavin kinase (RFK), Nox1, the Nox1 subunits
      (Rac1, Noxo1, and Noxa1), TNF receptor-associated death domain (TRADD), and TNF
      receptor-associated factor 2 (TRAF2). Depletion of RFK, but not the Nox1
      subunits, TRADD and TRAF2, failed to recruit Nox1 and Rac1 to DR4 and DR5,
      demonstrating that RFK plays an essential role in linking DR4/DR5 with Nox1.
      Knockdown studies also reveal that RFK, TRADD, and TRAF2 play critical,
      intermediate, and negligible roles, respectively, in the KD548-Fc-mediated ROS
      accumulation and downstream signaling. Binding assays using recombinantly
      expressed proteins suggest that DR4/DR5 directly interact with cytosolic RFK
      through RFK-binding regions within the intracellular death domains, and TRADD
      stabilizes the DR4/DR5-RFK complex. Our results suggest that DR4 and DR5 have a
      capability to activate Nox1 by recruiting RFK, resulting in ROS-mediated
      apoptotic cell death in tumor cells.

PMID- 22158616
TI  - Identification of functionally distinct TRAF proinflammatory and
      phosphatidylinositol 3-kinase/mitogen-activated protein kinase/extracellular
      signal-regulated kinase kinase (PI3K/MEK) transforming activities emanating from
      RET/PTC fusion oncoprotein.
AB  - Thyroid carcinomas that harbor RET/PTC oncogenes are well differentiated,
      relatively benign neoplasms compared with those expressing oncogenic RAS or BRAF
      mutations despite signaling through shared transforming pathways. A distinction,
      however, is that RET/PTCs induce immunostimulatory programs, suggesting that, in
      the case of this tumor type, the additional pro-inflammatory pathway reduces
      aggressiveness. Here, we demonstrate that pro-inflammatory programs are
      selectively activated by TRAF2 and TRAF6 association with RET/PTC oncoproteins.
      Eliminating this mechanism reduces pro-inflammatory cytokine production without
      decreasing transformation efficiency. Conversely, ablating MEK/ERK or PI3K/AKT
      signaling eliminates transformation but not pro-inflammatory cytokine secretion.
      Functional uncoupling of the two pathways demonstrates that intrinsic pro
      inflammatory pathways are not required for cellular transformation and suggests a
      need for further investigation into the role inflammation plays in thyroid tumor
      progression.

PMID- 22158617
TI  - Characterization of unique modification of flagellar rod protein FlgG by
      Campylobacter jejuni lipid A phosphoethanolamine transferase, linking bacterial
      locomotion and antimicrobial peptide resistance.
AB  - Gram-negative bacteria assemble complex surface structures that interface with
      the surrounding environment and are involved in pathogenesis. Recent work in
      Campylobacter jejuni identified a gene encoding a novel phosphoethanolamine
      (pEtN) transferase Cj0256, renamed EptC, that serves a dual role in modifying the
      flagellar rod protein, FlgG, and the lipid A domain of C. jejuni
      lipooligosaccharide with a pEtN residue. In this work, we characterize the unique
      post-translational pEtN modification of FlgG using collision-induced and electron
      transfer dissociation mass spectrometry, as well as a genetic approach using site
      directed mutagenesis to determine the site of modification. Specifically, we show
      that FlgG is modified with pEtN at a single site (Thr(75)) by EptC and
      demonstrate enzyme specificity by showing that EptC is unable to modify other
      amino acids (e.g. serine and tyrosine). Using Campylobacter strains expressing
      site-directed FlgG mutants, we also show that defects in motility arise directly
      from the loss of pEtN modification of FlgG. Interestingly, alignments of FlgG
      from most epsilon proteobacteria reveal a conserved site of modification.
      Characterization of EptC and its enzymatic targets expands on the increasingly
      important field of prokaryotic post-translational modification of bacterial
      surface structures and the unidentified role they may play in pathogenesis.

PMID- 22158618
TI  - Lectin site ligation of CR3 induces conformational changes and signaling.
AB  - Neutrophils provide an innate immune response to tissues infected with fungal
      pathogens such as Candida albicans. This response is tightly regulated in part
      through the interaction of integrins with extracellular matrix ligands that are
      distributed within infected tissues. The beta(2) integrin, CR3 (CD11b/CD18), is
      unique among integrins in containing a lectin-like domain that binds the fungal
      pathogen-associated molecular pattern beta-glucan and serves as the dominant
      receptor for recognition of fungal pathogens by human granulocytes. beta-Glucan,
      when isolated in soluble form, has been shown to be a safe and effective immune
      potentiator when administered therapeutically. Currently a pharmaceutical grade
      preparation of beta-glucan is in several clinical trials with an anti-cancer
      indication. CR3 binding of extracellular matrix, carbohydrate, or both ligands
      simultaneously differentially regulates neutrophil function through a mechanism
      not clearly understood. Using FRET reporters, we interrogated the effects of
      soluble beta-glucan on intracellular and extracellular CR3 structure. Although
      the canonical CR3 ligand fibrinogen induced full activation, beta-glucan alone or
      in conjunction with fibrinogen stabilized an intermediate conformation with
      moderate headpiece extension and full cytoplasmic tail separation. A set of
      phosphopeptides differentially regulated by beta-glucan in a CR3-dependent manner
      were identified using functional proteomics and found to be enriched for
      signaling molecules and proteins involved in transcriptional regulation, mRNA
      processing, and alternative splicing. These data confirm that CR3 is a signaling
      pattern recognition receptor for beta-glucan and represent the first direct
      evidence of soluble beta-glucan binding and affecting a signaling-competent
      intermediate CR3 conformation on living cells.

PMID- 22158619
TI  - Kinetics of the association/dissociation cycle of an ATP-binding cassette
      nucleotide-binding domain.
AB  - Most ATP binding cassette (ABC) proteins are pumps that transport substrates
      across biological membranes using the energy of ATP hydrolysis. Functional ABC
      proteins have two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP,
      but the molecular mechanism of nucleotide hydrolysis is unresolved. This is due
      in part to the limited kinetic information on NBD association and dissociation.
      Here, we show dimerization of a catalytically active NBD and follow in real time
      the association and dissociation of NBDs from the changes in fluorescence
      emission of a tryptophan strategically located at the center of the dimer
      interface. Spectroscopic and structural studies demonstrated that the tryptophan
      can be used as dimerization probe, and we showed that under hydrolysis conditions
      (millimolar MgATP), not only the dimer dissociation rate increases, but also the
      dimerization rate. Neither dimer formation or dissociation are clearly favored,
      and the end result is a dynamic equilibrium where the concentrations of monomer
      and dimer are very similar. We proposed that based on their variable rates of
      hydrolysis, the rate-limiting step of the hydrolysis cycle may differ among full
      length ABC proteins.

PMID- 22158620
TI  - Protein kinase D1 is essential for contraction-induced glucose uptake but is not
      involved in fatty acid uptake into cardiomyocytes.
AB  - Increased contraction enhances substrate uptake into cardiomyocytes via
      translocation of the glucose transporter GLUT4 and the long chain fatty acid
      (LCFA) transporter CD36 from intracellular stores to the sarcolemma.
      Additionally, contraction activates the signaling enzymes AMP-activated protein
      kinase (AMPK) and protein kinase D1 (PKD1). Although AMPK has been implicated in
      contraction-induced GLUT4 and CD36 translocation in cardiomyocytes, the precise
      role of PKD1 in these processes is not known. To study this, we triggered
      contractions in cardiomyocytes by electric field stimulation (EFS). First, the
      role of PKD1 in GLUT4 and CD36 translocation was defined. In PKD1 siRNA-treated
      cardiomyocytes as well as cardiomyocytes from PKD1 knock-out mice, EFS-induced
      translocation of GLUT4, but not CD36, was abolished. In AMPK siRNA-treated
      cardiomyocytes and cardiomyocytes from AMPKalpha2 knock-out mice, both GLUT4 and
      CD36 translocation were abrogated. Hence, unlike AMPK, PKD1 is selectively
      involved in glucose uptake. Second, we analyzed upstream factors in PKD1
      activation. Cardiomyocyte contractions enhanced reactive oxygen species (ROS)
      production. Using ROS scavengers, we found that PKD1 signaling and glucose uptake
      are more sensitive to changes in intracellular ROS than AMPK signaling or LCFA
      uptake. Furthermore, silencing of death-activated protein kinase (DAPK) abrogated
      EFS-induced GLUT4 but not CD36 translocation. Finally, possible links between
      PKD1 and AMPK signaling were investigated. PKD1 silencing did not affect AMPK
      activation. Reciprocally, AMPK silencing did not alter PKD1 activation. In
      conclusion, we present a novel contraction-induced ROS-DAPK-PKD1 pathway in
      cardiomyocytes. This pathway is activated separately from AMPK and mediates GLUT4
      translocation/glucose uptake, but not CD36 translocation/LCFA uptake.

PMID- 22158621
TI  - Exposing a hidden functional site of C-reactive protein by site-directed
      mutagenesis.
AB  - C-reactive protein (CRP) is a cyclic pentameric protein whose major binding
      specificity, at physiological pH, is for substances bearing exposed
      phosphocholine moieties. Another pentameric form of CRP, which exists at acidic
      pH, displays binding activity for oxidized LDL (ox-LDL). The ox-LDL-binding site
      in CRP, which is hidden at physiological pH, is exposed by acidic pH-induced
      structural changes in pentameric CRP. The aim of this study was to expose the
      hidden ox-LDL-binding site of CRP by site-directed mutagenesis and to generate a
      CRP mutant that can bind to ox-LDL without the requirement of acidic pH. Mutation
      of Glu(42), an amino acid that participates in intersubunit interactions in the
      CRP pentamer and is buried, to Gln resulted in a CRP mutant (E42Q) that showed
      significant binding activity for ox-LDL at physiological pH. For maximal binding
      to ox-LDL, E42Q CRP required a pH much less acidic than that required by wild
      type CRP. At any given pH, E42Q CRP was more efficient than wild-type CRP in
      binding to ox-LDL. Like wild-type CRP, E42Q CRP remained pentameric at acidic pH.
      Also, E42Q CRP was more efficient than wild-type CRP in binding to several other
      deposited, conformationally altered proteins. The E42Q CRP mutant provides a tool
      to investigate the functions of CRP in defined animal models of inflammatory
      diseases including atherosclerosis because wild-type CRP requires acidic pH to
      bind to deposited, conformationally altered proteins, including ox-LDL, and
      available animal models may not have sufficient acidosis or other possible
      modifiers of the pentameric structure of CRP at the sites of inflammation.

PMID- 22158622
TI  - Cooperative responses of multiple kinesins to variable and constant loads.
AB  - Microtubule-dependent transport is most often driven by collections of kinesins
      and dyneins that function in either a concerted fashion or antagonistically.
      Several lines of evidence suggest that cargo transport may not be influenced
      appreciably by the combined action of multiple kinesins. Yet, as in previous
      optical trapping experiments, the forces imposed on cargos will vary spatially
      and temporally in cells depending on a number of local environmental factors, and
      the influence of these conditions has been largely overlooked. Here, we
      characterize the dynamics of structurally defined complexes containing multiple
      kinesins under the controlled loads of an optical force clamp. While
      demonstrating that there are generic kinetic barriers that restrict the ability
      of multiple kinesins to cooperate productively, the spatial and temporal
      properties of applied loads is found to play an important role in the collective
      dynamics of multiple motor systems. We propose this dependence has implications
      for intracellular transport processes, especially for bidirectional transport.

PMID- 22158623
TI  - Caldesmon regulates axon extension through interaction with myosin II.
AB  - To begin the process of forming neural circuits, new neurons first establish
      their polarity and extend their axon. Axon extension is guided and regulated by
      highly coordinated cytoskeletal dynamics. Here we demonstrate that in hippocampal
      neurons, the actin-binding protein caldesmon accumulates in distal axons, and its
      N-terminal interaction with myosin II enhances axon extension. In cortical neural
      progenitor cells, caldesmon knockdown suppresses axon extension and neuronal
      polarity. These results indicate that caldesmon is an important regulator of axon
      development.

PMID- 22158624
TI  - Bone morphogenetic protein 4 promotes vascular smooth muscle contractility by
      activating microRNA-21 (miR-21), which down-regulates expression of family of
      dedicator of cytokinesis (DOCK) proteins.
AB  - The bone morphogenetic protein 4 (BMP4) signaling pathway plays a critical role
      in the promotion and maintenance of the contractile phenotype in vascular smooth
      muscle cell (vSMC). Misexpression or inactivating mutations of the BMP receptor
      gene can lead to dedifferentiation of vSMC characterized by increased migration
      and proliferation that is linked to vascular proliferative disorders. Previously
      we demonstrated that vSMCs increase microRNA-21 (miR-21) biogenesis upon BMP4
      treatment, which induces contractile gene expression by targeting programmed cell
      death 4 (PDCD4). To identify novel targets of miR-21 that are critical for
      induction of the contractile phenotype by BMP4, biotinylated miR-21 was expressed
      in vSMCs followed by an affinity purification of mRNAs associated with miR-21.
      Nearly all members of the dedicator of cytokinesis (DOCK) 180-related protein
      superfamily were identified as targets of miR-21. Down-regulation of DOCK4, -5,
      and -7 by miR-21 inhibited cell migration and promoted cytoskeletal organization
      by modulating an activity of small GTPase. Thus, this study uncovers a regulatory
      mechanism of the vSMC phenotype by the BMP4-miR-21 axis through DOCK family
      proteins.

PMID- 22158625
TI  - Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by
      activating AMP-activated protein kinase in renal epithelial cells.
AB  - Hydrogen sulfide, a signaling gas, affects several cell functions. We
      hypothesized that hydrogen sulfide modulates high glucose (30 mm) stimulation of
      matrix protein synthesis in glomerular epithelial cells. High glucose stimulation
      of global protein synthesis, cellular hypertrophy, and matrix laminin and type IV
      collagen content was inhibited by sodium hydrosulfide (NaHS), an H(2)S donor.
      High glucose activation of mammalian target of rapamycin (mTOR) complex 1
      (mTORC1), shown by phosphorylation of p70S6 kinase and 4E-BP1, was inhibited by
      NaHS. High glucose stimulated mTORC1 to promote key events in the initiation and
      elongation phases of mRNA translation: binding of eIF4A to eIF4G, reduction in
      PDCD4 expression and inhibition of its binding to eIF4A, eEF2 kinase
      phosphorylation, and dephosphorylation of eEF2; these events were inhibited by
      NaHS. The role of AMP-activated protein kinase (AMPK), an inhibitor of protein
      synthesis, was examined. NaHS dose-dependently stimulated AMPK phosphorylation
      and restored AMPK phosphorylation reduced by high glucose. Compound C, an AMPK
      inhibitor, abolished NaHS modulation of high glucose effect on events in mRNA
      translation as well as global and matrix protein synthesis. NaHS induction of
      AMPK phosphorylation was inhibited by siRNA for calmodulin kinase kinase beta,
      but not LKB1, upstream kinases for AMPK; STO-609, a calmodulin kinase kinase beta
      inhibitor, had the same effect. Renal cortical content of cystathionine beta
      synthase and cystathionine gamma-lyase, hydrogen sulfide-generating enzymes, was
      significantly reduced in mice with type 1 diabetes or type 2 diabetes, coinciding
      with renal hypertrophy and matrix accumulation. Hydrogen sulfide is a newly
      identified modulator of protein synthesis in the kidney, and reduction in its
      generation may contribute to kidney injury in diabetes.

PMID- 22158626
TI  - AMF-26, a novel inhibitor of the Golgi system, targeting ADP-ribosylation factor
      1 (Arf1) with potential for cancer therapy.
AB  - ADP-ribosylation factor 1 (Arf1) plays a major role in mediating vesicular
      transport. Brefeldin A (BFA), a known inhibitor of the Arf1-guanine nucleotide
      exchange factor (GEF) interaction, is highly cytotoxic. Therefore, interaction of
      Arf1 with ArfGEF is an attractive target for cancer treatment. However, BFA and
      its derivatives have not progressed beyond the pre-clinical stage of drug
      development because of their poor bioavailability. Here, we aimed to identify
      novel inhibitors of the Arf1-ArfGEF interaction that display potent antitumor
      activity in vivo but with a chemical structure distinct from that of BFA. We
      exploited a panel of 39 cell lines (termed JFCR39) coupled with a drug
      sensitivity data base and COMPARE algorithm, resulting in the identification of a
      possible novel Arf1-ArfGEF inhibitor AMF-26, which differed structurally from
      BFA. By using a pulldown assay with GGA3-conjugated beads, we demonstrated that
      AMF-26 inhibited Arf1 activation. Subsequently, AMF-26 induced Golgi disruption,
      apoptosis, and cell growth inhibition. Computer modeling/molecular dynamics (MD)
      simulation suggested that AMF-26 bound to the contact surface of the Arf1-Sec7
      domain where BFA bound. AMF-26 affected membrane traffic, including the cis-Golgi
      and trans-Golgi networks, and the endosomal systems. Furthermore, using AMF-26
      and its derivatives, we demonstrated that there was a significant correlation
      between cell growth inhibition and Golgi disruption. In addition, orally
      administrated AMF-26 (83 mg/kg of body weight; 5 days) induced complete
      regression of human breast cancer BSY-1 xenografts in vivo, suggesting that AMF
      26 is a novel anticancer drug candidate that inhibits the Golgi system, targeting
      Arf1 activation.

PMID- 22158627
TI  - Genomic promoter occupancy of runt-related transcription factor RUNX2 in
      Osteosarcoma cells identifies genes involved in cell adhesion and motility.
AB  - Runt-related transcription factors (RUNX1, RUNX2, and RUNX3) are key lineage
      specific regulators of progenitor cell growth and differentiation but also
      function pathologically as cancer genes that contribute to tumorigenesis. RUNX2
      attenuates growth and stimulates maturation of osteoblasts during bone formation
      but is also robustly expressed in a subset of osteosarcomas, as well as in
      metastatic breast and prostate tumors. To assess the biological function of RUNX2
      in osteosarcoma cells, we examined human genomic promoter interactions for RUNX2
      using chromatin immunoprecipitation (ChIP)-microarray analysis in SAOS-2 cells.
      Promoter binding of both RUNX2 and RNA polymerase II was compared with gene
      expression profiles of cells in which RUNX2 was depleted by RNA interference.
      Many RUNX2-bound loci (1550 of 2339 total) exhibit promoter occupancy by RNA
      polymerase II and contain the RUNX consensus motif 5'-((T/A/C)G(T/A/C)GG(T/G).
      Gene ontology analysis indicates that RUNX2 controls components of multiple
      signaling pathways (e.g. WNT, TGFbeta, TNFalpha, and interleukins), as well as
      genes linked to cell motility and adhesion (e.g. the focal adhesion-related genes
      FAK/PTK2 and TLN1). Our results reveal that siRNA depletion of RUNX2, PTK2, or
      TLN1 diminishes motility of U2OS osteosarcoma cells. Thus, RUNX2 binding to
      diverse gene loci may support the biological properties of osteosarcoma cells.

PMID- 22158629
TI  - Preparation, spectrochemical, and computational analysis of L-carnosine (2-[(3
      aminopropanoyl)amino]-3-(1H-imidazol-5-yl)propanoic acid) and its ruthenium (II)
      coordination complexes in aqueous solution.
AB  - This study reports the synthesis and characterization of novel ruthenium (II)
      complexes with the polydentate dipeptide, L-carnosine (2-[(3
      aminopropanoyl)amino]-3-(1H-imidazol-5-yl)propanoic acid). Mixed-ligand complexes
      with the general composition [ML(p)(Cl)(q)(H2O)(r)].xH2O (M = Ru(II); L = L
      carnosine; p = 3 - q; r = 0-1; and x = 1-3) were prepared by refluxing aqueous
      solutions of the ligand with equimolar amounts of ruthenium chloride (black-alpha
      form) at 60  degrees C for 36 h. Physical properties of the complexes were
      characterized by elemental analysis, DSC/TGA, and cyclic voltammetry. The
      molecular structures of the complexes were elucidated using UV-Vis, ATR-IR, and
      heteronuclear NMR spectroscopy, then confirmed by density function theory (DFT)
      calculations at the B3LYP/LANL2DZ level. Two-dimensional NMR experiments (1H
      COSY, 13C gHMBC, and 15N gHMBC) were also conducted for the assignment of
      chemical shifts and calculation of relative coordination-induced shifts (RCIS) by
      the complex formed. According to our results, the most probable coordination
      geometries of ruthenium in these compounds involve nitrogen (N1) from the
      imidazole ring and an oxygen atom from the carboxylic acid group of the ligand as
      donor atoms. Additional thermogravimetric and electrochemical data suggest that
      while the tetrahedral-monomer or octahedral-dimer are both possible structures of
      the formed complexes, the metal in either structure occurs in the 2+ oxidation
      state. Resulting RCIS values indicate that the amide-carbonyl, and the amino
      terminus of the dipeptide are not involved in chelation and these observations
      correlate well with theoretical shift predictions by DFT.

PMID- 22158628
TI  - Nitroalkenes confer acute cardioprotection via adenine nucleotide translocase 1.
AB  - Electrophilic nitrated lipids (nitroalkenes) are emerging as an important class
      of protective cardiovascular signaling molecules. Although species such as nitro
      linoleate (LNO(2)) and nitro-oleate can confer acute protection against cardiac
      ischemic injury, their mechanism of action is unclear. Mild uncoupling of
      mitochondria is known to be cardioprotective, and adenine nucleotide translocase
      1 (ANT1) is a key mediator of mitochondrial uncoupling. ANT1 also contains redox
      sensitive cysteines that may be targets for modification by nitroalkenes.
      Therefore, in this study we tested the hypothesis that nitroalkenes directly
      modify ANT1 and that nitroalkene-mediated cardioprotection requires ANT1. Using
      biotin-tagged LNO(2) infused into intact perfused hearts, we obtained mass
      spectrometric (MALDI-TOF-TOF) evidence for direct modification (nitroalkylation)
      of ANT1 on cysteine 57. Furthermore, in a cell model of ischemia-reperfusion
      injury, siRNA knockdown of ANT1 inhibited the cardioprotective effect of LNO(2).
      Although the molecular mechanism linking ANT1-Cys(57) nitroalkylation and
      uncoupling is not yet known, these data suggest that ANT1-mediated uncoupling may
      be a mechanism for nitroalkene-induced cardioprotection.

PMID- 22158630
TI  - A simple and highly selective receptor for iodide in aqueous solution.
AB  - We synthesized a simple fluorescent receptor 3 bearing two boronic acid groups as
      recognition sites. The recognition behaviour of receptor 3 towards various anions
      was evaluated in THF/H(2)O (1:1, v/v) solution. Receptor 3 showed high
      selectivity for iodide among a series of anions. Fluorescence spectroscopy and
      computational calculations revealed that the electrostatic interaction played a
      crucial role in its high selectivity for iodide.

PMID- 22158631
TI  - Degradable thermoresponsive polymers which display redox-responsive LCST
      behaviour.
AB  - Disulfide linkages were introduced into poly (N-isopropylacrylamide) by the
      polycondensation of a RAFT-derived, telechelic macromonomer to give degradable
      yet vinyl-based polymers. These polymers displayed a redox-sensitive lower
      critical solution temperature (LCST) with the shorter, degraded product
      displaying a higher LCST than its non-degraded counterpart.

PMID- 22158633
TI  - Development of the screening test for hearing problems.
AB  - PURPOSE: The goal of this study was to develop a brief self-assessment instrument
      to screen for communication problems and psychosocial adjustment to hearing
      impairment as part of a rehabilitative needs assessment. METHOD: A pseudorandom
      sample of 1,000 cases was drawn from a large, heterogeneous clinical database
      containing audiometric data and responses to the Communication Profile for the
      Hearing Impaired (CPHI; Erdman & Demorest, 1998a). Item response theory was used
      to derive item-characteristic curves, and item selection was based primarily on
      item discrimination. Internal consistency, factor structure, sensitivity, and
      specificity of 2 scales, Communication and Adjustment, were evaluated in a
      holdout sample of 319 cases from the same database. RESULTS: A 9-item
      Communication scale and an 11-item Adjustment scale both showed satisfactory
      internal consistency, and the 20-item test presented a clear 2-factor structure.
      Sensitivity and specificity functions and positive and negative predictive values
      indicated that the 2 scales could be used to identify the bottom 2 quartiles of
      the clinical population, as defined by factor scores on the CPHI. CONCLUSION: The
      2 scales of the Screening Test for Hearing Problems can be used to screen for
      communication and adjustment problems that warrant a comprehensive rehabilitative
      assessment.

PMID- 22158635
TI  - Including service learning in the undergraduate communication sciences and
      disorders curriculum: benefits, challenges, and strategies for success.
AB  - PURPOSE: To describe some of the benefits of service learning (SL),
      considerations in course development and construction, and implementation and
      outcomes of an SL course in the undergraduate communication sciences and
      disorders (CSD) program at a small, public university in northwest Washington.
      METHOD: A review of the literature on SL and a description of the author's
      experience in course development are provided on the basis of a computerized
      database search, library search, and discussions with the Western Washington
      University Center for Service Learning. CONCLUSIONS: Teaching an SL course can
      present challenges to both faculty and students; nonetheless, incorporating SL
      into the undergraduate CSD curriculum is an excellent way of enriching the
      academic experience and improving critical-thinking skills of young students. SL
      provides hands-on opportunities for students to apply what they are learning in
      their CSD classes to real-world contexts, gain a better understanding of course
      content through engagement in real situations, and integrate information from a
      variety of courses in and outside of their major.

PMID- 22158634
TI  - Cortical high-gamma responses in auditory processing.
AB  - PURPOSE: This tutorial provides an introduction to cortical auditory spectral
      responses, focusing on event-related activity in the high-gamma frequencies (60
      150 Hz), their recent emergence in neuroscience research, and potential clinical
      applications. METHOD: Auditory high-gamma responses are described and compared
      with traditional cortical evoked responses, including the auditory evoked N1
      response. Methods for acquiring and analyzing spectral responses, including time
      frequency analyses, are discussed and contrasted with more familiar time-domain
      averaging approaches. Four cases are presented illustrating high-gamma response
      patterns associated with normal and impaired auditory processing. CONCLUSIONS:
      Cortical auditory high-gamma responses may provide a useful clinical measure of
      auditory processing.

PMID- 22158636
TI  - Addressing qualified personnel shortages for children who are deaf or hard of
      hearing with an interdisciplinary service learning program.
AB  - PURPOSE: To describe the student training benefits for speech-language pathology
      graduate students involved in an interdisciplinary, community-based intervention
      program at a Midwestern university for families of preschool children who were
      deaf or hard of hearing (DHH) and auditory-based spoken language users. METHOD:
      The Auditory and Language Enriched Program was developed to provide graduate
      students with a clinically relevant service learning opportunity that also met
      some unique community needs of families in the community. Specifically, students
      learned to provide families with imaginative ways to expose their children who
      were DHH to language and literacy and nurture their natural curiosity and zest
      for learning. RESULTS: Statistically significant improvement was noted between
      pre- and postintervention questionnaires of knowledge and skill related to
      intervention for this population by a single group of students. CONCLUSIONS: An
      interdisciplinary service learning approach to intervention might provide
      opportunities for university graduate programs to address the immediate and long
      term needs of families who have chosen a spoken language outcome for their young
      children who are DHH while simultaneously providing invaluable experience with
      low-incidence populations for their preservice graduate students.

PMID- 22158637
TI  - The promise of service learning in a pediatric audiology course on clinical
      training with the pediatric population.
AB  - PURPOSE: This study investigated the effectiveness of service learning (SL) and
      its impact on students' clinical competency, interest in pediatric audiology as a
      career, and levels of community engagement, as well as its impact on the
      community. METHOD: Forty-eight students enrolled in an SL pediatric audiology
      course providing hearing and middle ear testing to 292 children, ages 6 months to
      5 years. Another 10 non-SL students served as a control group. SL surveys were
      administered to students before and after the SL experience and post hoc to the
      non-SL group to assess their perceived readiness for evaluating children and
      their interest in pediatric audiology. Parents and community partner staff
      members completed another survey to provide feedback about their experience with
      the SL activity. RESULTS: The students' ratings were higher post-SL than pre-SL,
      and their learning gain was positively ranked post-SL compared with the non-SL
      group. Also, 71% of the SL students expressed positive interest in pediatric
      audiology post-SL compared with 37% of the non-SL group. Responses from community
      partners were also positive. CONCLUSIONS: Embedding SL into a pediatric audiology
      course increased student interest in pediatric audiology as a career and enhanced
      readiness to evaluate young children.

PMID- 22158638
TI  - Service learning in auditory rehabilitation courses: the University of Texas at
      Dallas.
AB  - PURPOSE: The aim of this work was to review service learning (SL) principles and
      its implementation into the auditory rehabilitation (AR) curriculum at the
      University of Texas at Dallas and to evaluate the courses to determine whether
      potential benefits of SL are worth the substantial time commitment and course
      restructuring. METHOD: Via retrospective review, student outcomes for 25 students
      from 3 cohorts who completed the adult AR course prior to implementation of SL
      curriculum (pre-SL) were compared with those of 28 students from 3 SL cohorts.
      Data included final examination grades, ratings for overall course content,
      amount learned, clarity of responsibility, workload, relevance, and course
      comments. Student journals from the SL group and mentor surveys also were
      reviewed. RESULTS: The majority of student outcomes were comparable for pre-SL
      and SL cohorts. Clarity of responsibility and workload were rated lower for SL
      courses than for pre-SL classes, with medium and small to medium effect sizes,
      respectively. Mentors rated the projects and process of high value and benefit,
      and several projects remain in use beyond the end of the course. CONCLUSION:
      Continued use of an SL approach is supported, but additional guidance for
      students is needed for reflection and project analysis.

PMID- 22158639
TI  - Ultrasensitive electrochemiluminescence immunoassay for tumor marker detection
      using functionalized Ru-silica@nanoporous gold composite as labels.
AB  - In this work, we reported a simple and sensitive sandwich-type
      electrochemiluminescence (ECL) immunosensor for carcinoembryonic antigen (CEA) on
      a gold nanoparticles (AuNPs) modified glassy carbon electrode (GCE). The Ru
      silica (Ru(bpy)(3)(2+)-doped silica) capped nanoporous gold (NPG) (Ru-silica@NPG)
      composite was used as an excellent label with amplification techniques. The NPG
      was prepared with a simple dealloying strategy, by which silver was dissolved
      from silver/gold alloys in nitric acid. The primary antibody was immobilized on
      the AuNPs modified electrode through l-cysteine and glutaraldehyde, and then the
      antigen and the functionalized Ru-silica@NPG composite labeled secondary antibody
      were conjugated successively to form a sandwich-type immunocomplex through the
      specific interaction. The concentrations of CEA were obtained in the range from 1
      pg mL(-1) to 10 ng mL(-1) with a detection limit of 0.8 pg mL(-1). The as
      proposed ECL immunosensor has the advantages of high sensitivity, specificity and
      stability and could become a promising technique for tumor marker detection.

PMID- 22158641
TI  - How is slow wave sleep related to hypertension?

PMID- 22158642
TI  - Pin1 as a protector of vascular endothelial homeostasis.

PMID- 22158644
TI  - Preterm birth: a novel risk factor for higher blood pressure in later life.

PMID- 22158643
TI  - Systematic review and meta-analysis of preterm birth and later systolic blood
      pressure.
AB  - Lower birth weight because of fetal growth restriction is associated with higher
      blood pressure later in life, but the extent to which preterm birth (<37
      completed weeks' gestation) or very low birth weight (<1500 g) predicts higher
      blood pressure is less clear. We performed a systematic review of 27
      observational studies that compared the resting or ambulatory systolic blood
      pressure or diagnosis of hypertension among children, adolescents, and adults
      born preterm or very low birth weight with those born at term. We performed a
      meta-analysis with the subset of 10 studies that reported the resting systolic
      blood pressure difference in millimeters of mercury with 95% CIs or SEs. We
      assessed methodologic quality with a modified Newcastle-Ottawa Scale. The 10
      studies were composed of 1342 preterm or very low birth weight and 1738 term
      participants from 8 countries. The mean gestational age at birth of the preterm
      participants was 30.2 weeks (range: 28.8-34.1 weeks), birth weight was 1280 g
      (range: 1098-1958 g), and age at systolic blood pressure measurement was 17.8
      years (range: 6.3-22.4 years). Former preterm or very low birth weight infants
      had higher systolic blood pressure than term infants (pooled estimate: 2.5 mm Hg
      [95% CI: 1.7-3.3 mm Hg]). For the 5 highest quality studies, the systolic blood
      pressure difference was slightly greater, at 3.8 mm Hg (95% CI: 2.6-5.0 mm Hg).
      We conclude that infants who are born preterm or very low birth weight have
      modestly higher systolic blood pressure later in life and may be at increased
      risk for developing hypertension and its sequelae.

PMID- 22158645
TI  - Sex-specific influence of angiotensin type 2 receptor stimulation on renal
      function: a novel therapeutic target for hypertension.
AB  - The renin-angiotensin system is a powerful regulator of arterial pressure and
      body fluid volume. Increasing evidence suggests that the angiotensin type 2
      receptor (AT(2)R), which mediates the vasodilatory and natriuretic actions of
      angiotensin peptides, is enhanced in females and may, therefore, represent an
      innovative therapeutic target. We investigated the therapeutic potential of
      direct AT(2)R stimulation on renal function in 11- to 12-week-old anesthetized
      male and female Sprague-Dawley rats. Renal blood flow was examined in response to
      a graded infusion of the highly selective, nonpeptide AT(2)R agonist, compound 21
      (100, 200, and 300 ng/kg per minute), in the presence and absence of AT(2)R
      blockade (PD123319; 1 mg/kg per hour). Direct AT(2)R stimulation significantly
      increased renal blood flow in both males and females, without influencing
      arterial pressure. This was dose dependent in females only and occurred to a
      greater extent in females at the highest dose of compound 21 administered (males:
      13.1+/-2.4% versus females: 23.0+/-3.2% change in renal blood flow at 300 ng/kg
      per minute versus baseline; P<0.01). In addition, AT(2)R stimulation
      significantly increased sodium and water excretion to a similar extent in males
      and females (P(Group)=0.05 and 0.005). However, there was no significant change
      in glomerular filtration rate in either sex, suggesting that altered tubular
      function may be responsible for AT(2)R-induced natriuresis rather than
      hemodynamic effects. Taken together, this study provides evidence that direct
      AT(2)R stimulation produces vasodilatory and natriuretic effects in the male and
      female kidney. The AT(2)R may, therefore, represent a valuable therapeutic target
      for the treatment of renal and cardiovascular diseases in both men and women.

PMID- 22158646
TI  - PKC-ing is believing: targeting protein kinase C in heart failure.

PMID- 22158647
TI  - Mitochondrial angiotensin receptors and aging.

PMID- 22158648
TI  - Elizabeth McNally: taking on inherited cardiovascular disorders. Interviewed by
      Alice McCarthy.

PMID- 22158650
TI  - Signaling during epicardium and coronary vessel development.
AB  - The epicardium, the tissue layer covering the cardiac muscle (myocardium),
      develops from the proepicardium, a mass of coelomic progenitors located at the
      venous pole of the embryonic heart. Proepicardium cells attach to and spread over
      the myocardium to form the primitive epicardial epithelium. The epicardium
      subsequently undergoes an epithelial-to-mesenchymal transition to give rise to a
      population of epicardium-derived cells, which in turn invade the heart and
      progressively differentiate into various cell types, including cells of coronary
      blood vessels and cardiac interstitial cells. Epicardial cells and epicardium
      derived cells signal to the adjacent cardiac muscle in a paracrine fashion,
      promoting its proliferation and expansion. Recently, high expectations have been
      raised about the epicardium as a candidate source of cells for the repair of the
      damaged heart. Because of its developmental importance and therapeutic potential,
      current research on this topic focuses on the complex signals that control
      epicardial biology. This review describes the signaling pathways involved in the
      different stages of epicardial development and discusses the potential of
      epicardial signals as targets for the development of therapies to repair the
      diseased heart.

PMID- 22158651
TI  - Suicide in Asia: opportunities and challenges.
AB  - Asian countries account for approximately 60% of the world's suicides, but there
      is a great mismatch in the region between the scale of the problem and the
      resources available to tackle it. Despite certain commonalities, the continent
      itself is culturally, economically, and socially diverse. This paper reviews
      current epidemiologic patterns of suicide, including suicide trends,
      sociodemographic factors, urban/rural living, suicide methods, sociocultural
      religious influences, and risk and protective factors in Asia, as well as their
      implications. The observed epidemiologic distributions of suicides reflect
      complex interplays among the traditional value/culture system, rapid economic
      transitions under market globalization, availability/desirability of suicide
      methods, and sociocultural permission/prohibitions regarding suicides. In
      general, compared with Western countries, Asian countries still have a higher
      average suicide rate, lower male-to-female suicide gender ratio, and higher
      elderly-to-general-population suicide ratios. The role of mental illness in
      suicide is not as important as that in Western countries. In contrast, aggravated
      by access to lethal means in Asia (e.g., pesticide poisoning and jumping), acute
      life stress (e.g., family conflicts, job and financial security issues) plays a
      more important role than it does in Western countries. Some promising suicide
      prevention programs in Asia are illustrated. Considering the specific
      socioeconomic and cultural aspects of the region, community-based suicide
      intervention programs integrating multiple layers of intervention targets may be
      the most feasible and cost-effective strategy in Asia, with its populous areas
      and limited resources.

PMID- 22158652
TI  - Synthesis of new substituted chromen[4,3-c]pyrazol-4-ones and their antioxidant
      activities.
AB  - A series of new coumarin derivatives 4 containing a 4-arylbut-3-en-2-one moiety
      were synthesized by condensation of 3-acetylcoumarin 1 with aryl aldehydes 2 in
      chloroform in the presence of piperidine. The interactions of 3-formyl-4
      chlorocoumarin (3) with nitrogen-containg nucleophiles leading to the
      corresponding substituted chromen-[4,3-c]pyrazol-4-ones 5 are described. The
      structures of the obtained compounds were established on the basis of 1D NMR, 2D
      NMR and IR and further the compounds were evaluated for possible antioxidant
      activities. The coumarinic chalcone 4a has been found to be the most active (IC50
      = 2.07 MUM) in this study.

PMID- 22158649
TI  - Empowering adult stem cells for myocardial regeneration.
AB  - Treatment strategies for heart failure remain a high priority for ongoing
      research due to the profound unmet need in clinical disease coupled with lack of
      significant translational progress. The underlying issue is the same whether the
      cause is acute damage, chronic stress from disease, or aging: progressive loss of
      functional cardiomyocytes and diminished hemodynamic output. To stave off
      cardiomyocyte losses, a number of strategic approaches have been embraced in
      recent years involving both molecular and cellular approaches to augment
      myocardial structure and performance. Resultant excitement surrounding
      regenerative medicine in the heart has been tempered by realizations that
      reparative processes in the heart are insufficient to restore damaged myocardium
      to normal functional capacity and that cellular cardiomyoplasty is hampered by
      poor survival, proliferation, engraftment, and differentiation of the donated
      population. To overcome these limitations, a combination of molecular and
      cellular approaches must be adopted involving use of genetic engineering to
      enhance resistance to cell death and increase regenerative capacity. This review
      highlights biological properties of approached to potentiate stem cell-mediated
      regeneration to promote enhanced myocardial regeneration, persistence of donated
      cells, and long-lasting tissue repair. Optimizing cell delivery and harnessing
      the power of survival signaling cascades for ex vivo genetic modification of stem
      cells before reintroduction into the patient will be critical to enhance the
      efficacy of cellular cardiomyoplasty. Once this goal is achieved, then cell-based
      therapy has great promise for treatment of heart failure to combat the loss of
      cardiac structure and function associated with acute damage, chronic disease, or
      aging.

PMID- 22158653
TI  - Common structural and epigenetic changes in the genome of castration-resistant
      prostate cancer.
AB  - Progression of primary prostate cancer to castration-resistant prostate cancer
      (CRPC) is associated with numerous genetic and epigenetic alterations that are
      thought to promote survival at metastatic sites. In this study, we investigated
      gene copy number and CpG methylation status in CRPC to gain insight into specific
      pathophysiologic pathways that are active in this advanced form of prostate
      cancer. Our analysis defined and validated 495 genes exhibiting significant
      differences in CRPC in gene copy number, including gains in androgen receptor
      (AR) and losses of PTEN and retinoblastoma 1 (RB1). Significant copy number
      differences existed between tumors with or without AR gene amplification,
      including a common loss of AR repressors in AR-unamplified tumors. Simultaneous
      gene methylation and allelic deletion occurred frequently in RB1 and HSD17B2, the
      latter of which is involved in testosterone metabolism. Lastly, genomic DNA from
      most CRPC was hypermethylated compared with benign prostate tissue. Our findings
      establish a comprehensive methylation signature that couples epigenomic and
      structural analyses, thereby offering insights into the genomic alterations in
      CRPC that are associated with a circumvention of hormonal therapy. Genes
      identified in this integrated genomic study point to new drug targets in CRPC, an
      incurable disease state which remains the chief therapeutic challenge.

PMID- 22158655
TI  - Transition metal ion-substituted polyoxometalates entrapped in polypyrrole as an
      electrochemical sensor for hydrogen peroxide.
AB  - A conducting polymer was used for the immobilization of various transition metal
      ion-substituted Dawson-type polyoxometalates (POMs) onto glassy carbon
      electrodes. Voltammetric responses of films of different thicknesses were stable
      within the pH domain 2-7 and reveal redox processes associated with the
      conducting polymer, the entrapped POMs and incorporated metal ions. The resulting
      POM doped polypyrrole films were found to be extremely stable towards redox
      switching between the various redox states associated with the incorporated POM.
      An amperometric sensor for hydrogen peroxide detection based upon the POM doped
      polymer films was investigated. The detection limits were 0.3 and 0.6 MUM, for
      the Cu(2+)- and Fe(3+)-substituted POM-doped polypyrrole films respectively, with
      a linear region from 0.1 up to 2 mM H(2)O(2). Surface characterization of the
      polymer films was carried out using atomic force microscopy, X-ray photoelectron
      spectroscopy and scanning electron microscopy.

PMID- 22158656
TI  - UV light-emitting-diode photochemical mercury vapor generation for atomic
      fluorescence spectrometry.
AB  - A new, miniaturized and low power consumption photochemical vapor generation
      (PVG) technique utilizing an ultraviolet light-emitting diode (UV-LED) lamp is
      described, and further validated via the determination of trace mercury. In the
      presence of formic acid, the mercury cold vapor is favourably generated from
      Hg(2+) solutions by UV-LED irradiation, and then rapidly transported to an atomic
      fluorescence spectrometer for detection. Optimum conditions for PVG and
      interferences from concomitant elements were investigated in detail. Under
      optimum conditions, a limit of detection (LOD) of 0.01 MUg L(-1) was obtained,
      and the precision was better than 3.2% (n = 11, RSD) at 1 MUg L(-1) Hg(2+). No
      obvious interferences from any common ions were evident. The methodology was
      successfully applied to the determination of mercury in National Research Council
      Canada DORM-3 fish muscle tissue and several water samples.

PMID- 22158657
TI  - Fluorometric, water-based sensors for the detection of nerve gas G mimics DMMP,
      DCP and DCNP.
AB  - Water-based Zn(II) bisterpyridine systems were used as fluorometric sensors for
      the detection of the nerve gas G mimics DMMP, DCP and DCNP. Analyte
      concentrations in the range of 10(-7) to 10(-6) M are detectable in solution. The
      utilization of a test stripe additionally allows the detection of
      organophosphonates from the gas phase.

PMID- 22158658
TI  - Silica encapsulated SERS nanoprobe conjugated to the bacteriophage tailspike
      protein for targeted detection of Salmonella.
AB  - Silica-encapsulated Raman-reporter embedded SERS nanoprobes, named nanoaggregate
      embedded beads (NAEBs), were conjugated to the Salmonella specific tailspike
      protein (TSP) isolated from the P22 bacteriophage to enable a highly specific and
      ultrasensitive optical transduction platform. We demonstrate three successful
      surface conjugation strategies and highlight the detection of a single bacterium
      using SERS.

PMID- 22158659
TI  - Sleep epidemiology--a rapidly growing field.

PMID- 22158660
TI  - Commentary: Hogben vs the Tyranny of averages.

PMID- 22158661
TI  - Reproductive history and mortality from cardiovascular disease among women
      textile workers in Shanghai, China.
AB  - BACKGROUND: Few studies have examined the possible effects of reproductive
      factors on cardiovascular disease (CVD) risks in Asian women. METHODS: A cohort
      of 267,400 female textile workers in Shanghai, China, was administered a
      questionnaire at enrolment (1989-91) and followed for mortality through 2000.
      Relative risks (hazard ratios) for ischaemic heart disease (IHD), ischaemic
      stroke and haemorrhagic stroke were calculated using Cox proportional hazards
      modelling, adjusting for relevant co-variates. RESULTS: Risks were not
      consistently associated with age at menopause, parity, stillbirths, miscarriages
      or duration of lactation. An increasing trend in IHD mortality risk, but not
      stroke, was observed with decreasing age at menarche. There was no evidence of
      increased CVD mortality risk by oral or injectable contraceptive use or induced
      abortions. As expected, greater mortality rates from CVD and increased CVD risks
      were also observed with smoking. CONCLUSIONS: Use of steroid contraceptives,
      induced abortions and reduced parity from China's one-child-per-family policy has
      not had an adverse effect on risk of CVD mortality in this cohort.

PMID- 22158662
TI  - Premature cardiovascular mortality and alcohol consumption before death in
      Arkhangelsk, Russia: an analysis of a consecutive series of forensic autopsies.
AB  - BACKGROUND: High cardiovascular diseases (CVD) mortality among the middle aged is
      a major cause of reduced life expectancy in Russia, especially among men.
      Hazardous alcohol consumption is suspected to be a powerful contributing factor.
      METHODS: All men (1099) and women (519) aged 30-70 years who died between 1
      January 2008 and 31 August 2009 from CVD in the city of Arkhangelsk, north-west
      Russia, were included. CVD mortality was stratified by age, gender and diagnosis.
      For the cases diagnosed by forensic pathologists, the blood alcohol concentration
      (BAC) was determined. The forensic autopsy rate was 72% for men and 62% for
      women. RESULTS: Age-standardized CVD mortality rate (all age groups) in men was
      higher than in women. The largest male-female ratio (4.3) was observed in the age
      group of 50-59 years. Alcoholic and unspecified cardiomyopathies were the most
      dominant of CVD mortalities in women, and second in men aged <50 years; they
      accounted for 50 and 25% of deaths, respectively. About one-third of men and
      women who died from CVD aged <60 years had consumed alcohol shortly before death.
      This occurred most frequently among the diagnostic groups 'other acute or
      subacute cardiac ischaemia', 'atherosclerotic heart disease' and
      'cardiomyopathies'. Alcohol was more likely to be found at autopsy in men than in
      women (odds ratio 1.55; 95% confidence interval 1.14-2.10). No difference was
      found for those who died from myocardial infarction, cerebrovascular diseases and
      cardiomyopathies. Of the deceased, <1% had a BAC of >= 4 g/l. CONCLUSIONS: A high
      proportion of subjects who died from CVD in Arkhangelsk consumed alcohol shortly
      before death. It was highest among males aged 50-59 years. The largest gender
      difference in mortality, highest absolute number of premature CVD deaths, and the
      highest proportion of alcohol-positive autopsies occurred among them. Since
      associations with alcohol consumption varied considerably between the types of
      CVD diagnoses, this observation should be taken into account when planning future
      research. Our study does not provide evidence that cardiovascular deaths are
      misclassified cases of acute alcohol poisoning.

PMID- 22158663
TI  - The inverse relationship between alanine aminotransferase in the normal range and
      adverse cardiovascular and non-cardiovascular outcomes.
AB  - BACKGROUND: High serum alanine aminotransferase (ALT) levels have been associated
      with increased risk of diabetes and with increased mortality, but associations of
      variations of ALT in the normal range with outcomes have been less well studied.
      METHODS: We studied the relationship between ALT, mortality and cardiovascular
      events in the West of Scotland Coronary Prevention Study (WOSCOPS) and the
      Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trials that
      explicitly excluded subjects with clinically significant liver damage, plus the
      Leiden 85-plus, a study of survivors to age 85 years. The associations between
      ALT and morbidity and mortality outcomes were investigated using Cox proportional
      hazard models adjusting for a comprehensive panel of cardiovascular risk factors.
      RESULTS: In all three study cohorts, ALT displayed an independent inverse
      relationship with all-cause mortality so that hazard ratios for fourth versus
      first quarter of ALT were all below 1.0; HRs 0.64 [95% confidence interval (CI)
      0.50-0.81], 0.86 (0.73-1.01), 0.66 (0.50-0.87); WOSCOPS, PROSPER, Leiden 85-plus,
      respectively. In WOSCOPS and PROSPER, ALT was also inversely associated with risk
      of fatal plus non-fatal cardiovascular events, including coronary heart disease
      (CHD) events and stroke. CONCLUSIONS: In three independent populations, ALT in
      the normal range displayed an inverse relationship with total mortality,
      cardiovascular events and non-cardiovascular events in middle-to-older aged
      subjects without evidence of clinically significant liver damage, independent of
      traditional cardiovascular and other risk factors. These findings indicate that
      the relationship between ALT and clinical outcomes is more complex than generally
      appreciated.

PMID- 22158664
TI  - Commentary: Liver enzymes and the risk of adverse cardiovascular outcomes--the
      lower, the better?

PMID- 22158665
TI  - Is there a divergence in time trends in the prevalence of impaired glucose
      tolerance and diabetes? A systematic review in South Asian populations.
AB  - OBJECTIVE: Recently, diabetes prevalence has increased in South Asians making it
      a global public health priority. There are suggestions that pre-diabetes,
      including impaired glucose tolerance (IGT), may not be increasing. We conducted a
      systematic review to explore the paradox. Research Design and Methods We searched
      electronic databases from inception to June 2009 for cross-sectional studies
      providing prevalence of pre-diabetes (using WHO criteria) in South Asian adult
      populations. Two reviewers independently screened articles, performed data
      extraction, quality appraisal and study classification with any discrepancies
      resolved by consensus. Repeated cross-sectional studies, categorized by pre
      specified criteria, were used for the primary analysis, supplemented by analysis
      of comparable and all studies. RESULTS: In total, 79 cross-sectional data sets
      (from 69 published studies) were identified resulting in the inclusion of 179 408
      people. Four sets of repeated cross-sectional studies, conducted in Chennai,
      rural Tamil Nadu, Mauritius and Singapore (n = 30,399), provided time trend
      information. Three of them showed an increase in diabetes prevalence (P < 0.001)
      whereas IGT fell in two (P < 0.05), and was stable in the remainder. A similar
      pattern was seen among three other sets of comparable studies (n = 58,820) and in
      scatterplots of all 79 data sets. CONCLUSION: This novel systematic review is the
      first to assess secular trends of pre-diabetes in any population. The data show
      diabetes prevalence is rising, whereas IGT prevalence is stable or falling.
      Explanations include: recent environmental or lifestyle changes favouring an
      increased rate of conversion from IGT to diabetes, or a cohort effect with
      improving maternal and infant nutrition resulting in reduced IGT with a fall in
      diabetes to follow.

PMID- 22158666
TI  - Commentary: Trends in prevalence of type 2 diabetes and prediabetes in South
      Asians--does it tell a story?

PMID- 22158667
TI  - Lifecourse infectious origins of sexual inequalities in central adiposity.
AB  - BACKGROUND: Social disparities in obesity are often more marked among women than
      men, possibly due to social factors. Taking a life-history perspective, we
      hypothesized that childhood infections could be relevant via sex-specific effects
      of immune system activation on sexual development and, hence, body shape.
      METHODS: We used multivariable linear regression to assess the sex-specific,
      adjusted associations of 'childhood' pathogens [0 (n = 1002), 1 (n = 2199), 2 (n
      = 3442) or 3 (n = 4833) of HSV1, CMV and hepatitis A antibodies] and 'adult'
      pathogens [0 (n = 5836), 1 (n = 3018) or >= 2 (n = 720) of HSV2, HHV8 and
      hepatitis B or C) with waist-hip ratio (WHR) and body mass index (BMI) standard
      deviations (SDs) using NHANES III (1988-94). As validation, we assessed
      associations with height. RESULTS: 'Childhood' pathogens were positively
      associated with WHR among women [0.18 SD, 95% confidence interval (95% CI) 0.04
      0.32 for 3, compared with 0], but not men (-0.04 SD, 95% CI -0.15 to 0.08),
      adjusted for age, education, race/ethnicity, smoking and alcohol. Further
      adjustments for leg length barely changed the estimates. There were no such sex
      specific associations for BMI or for adult pathogens. 'Childhood', but not
      'adult', pathogens were negatively associated with height, adjusted for age, sex,
      education and race/ethnicity. CONCLUSIONS: These observations are consistent with
      the lifecourse hypothesis that early exposure to infections makes women
      vulnerable to central obesity. This hypothesis potentially sheds new light on the
      developmental origins of obesity, and is consistent with the generally higher
      levels of central obesity among women than men in developing populations.

PMID- 22158668
TI  - Juvenile delinquency, social background and suicide--a Swedish national cohort
      study of 992,881 young adults.
AB  - BACKGROUND: As the suicide rates in young adults do not show a clear decline, it
      is important to elucidate possible risk factors. Juvenile delinquency has been
      pointed out as a possible risk behaviour. METHODS: This register-based cohort
      study comprises the birth cohorts between 1972 and 1981 in Sweden. We followed
      992,881 individuals from the age of 20 years until 31 December 2006, generating
      10 210 566 person-years and 1482 suicides. Juvenile delinquency was defined as
      being convicted of a crime between the ages of 15 and 19 years. Estimates of risk
      of suicide were calculated as incidence rate ratio (IRR) with 95% confidence
      intervals (CIs) using Poisson regression analysis with adjustment for potential
      confounding by their own and their parents' mental illness or substance abuse,
      parental education, single parenthood, social assistance, adoption and foster
      care. RESULTS: Among females, 5.9%, and among males, 17.9%, had at least one
      conviction between the ages 15 and 19 years. In the fully adjusted model, females
      with one conviction had a suicide risk of 1.7 times higher (95% CI 1.2-2.4), the
      corresponding IRR for men was 2.0 (95% CI 1.7-2.4) and 5.7 (95% CI 2.5-13.1) and
      6.6 (95% CI 5.2-8.3), for women and men with five or more convictions. The effect
      of severe delinquency on suicide was independent of parental educational level.
      CONCLUSIONS: This study supports the hypothesis that individuals with delinquent
      behaviour in late adolescence have an increased risk of suicide as young adults.
      Regardless of causality issues, repeated juvenile offenders should be regarded by
      professionals in health, social and correctional services who come into contact
      with this group as a high-risk group for suicide.

PMID- 22158669
TI  - Critical windows of exposure for arsenic-associated impairment of cognitive
      function in pre-school girls and boys: a population-based cohort study.
AB  - BACKGROUND: Exposure to arsenic through drinking water has been associated with
      impaired cognitive function in school-aged children in a few cross-sectional
      studies; however, there is little information on critical windows of exposure.
      METHODS: We conducted a population-based longitudinal study in rural Bangladesh.
      We assessed the association of arsenic exposure, based on urinary arsenic (U-As;
      twice during pregnancy and twice in childhood), with the development of about
      1700 children at 5 years of age using Wechsler Pre-school and Primary Scale of
      Intelligence [intelligence quotient (IQ)]. RESULTS: Median maternal U-As in
      pregnancy was 80 ug/l (10-90 percentiles: 25-400 ug/l). Children's urine
      contained 35 (12-155) ug/l and 51 (20-238) ug/l at 1.5 and 5 years, respectively.
      Using multivariable-adjusted regression analyses, controlling for all potential
      confounders and loss to follow-up, we found that verbal IQ (VIQ) and full scale
      IQ (FSIQ) were negatively associated with (log) U-As in girls. The associations
      were consistent, but somewhat stronger with concurrent arsenic exposure [VIQ: B =
      -2.4, 95% confidence interval (CI) = -3.8 to -1.1; FSIQ: B = -1.4, 95% CI = -2.7
      to -0.1, n = 817), compared with that at 1.5 years (VIQ: B = -0.85, 95% CI = -2.1
      to 0.4; FSIQ: B = -0.74, 95% CI = -1.9 to 0.4, n = 902), late gestation (VIQ: B =
      -1.52, 95% CI = -2.6 to -0.4; FSIQ: B = -1.35, 95% CI = -2.4 to -0.3, n = 874)
      and early gestation (VIQ: B = -1.23, 95% CI = -2.4 to -0.06; FSIQ: B = -0.92, 95%
      CI = -2.0 to -0.2, n = 833). In boys, U-As showed consistently low and non
      significant associations with all IQ measures. An effect size calculation
      indicated that 100 ug/l U-As was associated with a decrement of 1-3 points in
      both VIQ and FSIQ in girls. CONCLUSION: We found adverse effects of arsenic
      exposure on IQ in girls, but not boys, at 5 years of age.

PMID- 22158670
TI  - Long-term antioxidant supplementation has no effect on health-related quality of
      life: the randomized, double-blind, placebo-controlled, primary prevention
      SU.VI.MAX trial.
AB  - BACKGROUND: The effect of antioxidant vitamin and mineral supplementation on
      health is one of the most controversial issues in human nutrition. Our objective
      was to investigate the effect of nutritional doses of a combination of
      antioxidant vitamins and minerals on health-related quality of life (HRQoL) in a
      sample of healthy French adults. METHODS: SU.VI.MAX is a randomized, double
      blind, placebo-controlled, primary prevention trial in which a total of 8112
      participants received a single capsule daily containing either placebo or vitamin
      C 120 mg, vitamin E 30 mg, beta-carotene 6 mg, selenium 100 MUg and zinc 20 mg.
      Participants completed HRQoL questionnaires (SF36 and GHQ12) at baseline and
      after a mean of 76.0 +/- 4.2 months. RESULTS: Scores for physical dimensions
      tended to decrease over time, whereas those for mental dimensions tended to
      improve. No differences in changes over time were observed between the supplement
      and placebo groups. Participants who believed that they received placebo had
      lower HRQoL scores than did those who thought they had received supplements [SF36
      Bodily pain (-3.3), General health (-2.2), Vitality (-1.6) dimensions and
      physical component summary score (-1.1) in men, and in SF36 Social functioning (
      2.3), General health (-1.4) dimensions and physical component summary score (
      0.7) in women]. CONCLUSIONS: Long-term supplementation with antioxidant vitamins
      and minerals had no beneficial effect on HRQoL in this trial. This is contrary to
      conventional beliefs and claims that such an effect exists. Trial Registration
      "Primary Prevention Trial of the Health Effects of Antioxidant Vitamins and
      Minerals." NTC n 00272428 http://www.clinicaltrials.gov.

PMID- 22158671
TI  - Participant identification in genetic association studies: improved methods and
      practical implications.
AB  - BACKGROUND: In a recent paper by Homer et al. (Resolving individuals contributing
      trace amounts of DNA to highly complex mixtures using high-density SNP genotyping
      microarrays. PLoS Genet 2008;4:e1000167), a method for detecting whether a given
      individual is a contributor to a particular genomic mixture was proposed. This
      prompted grave concern about the public dissemination of aggregate statistics
      from genome-wide association studies. It is of clear scientific importance that
      such data be shared widely, but the confidentiality of study participants must
      not be compromised. The issue of what summary genomic data can safely be posted
      on the web is only addressed satisfactorily when the theoretical underpinnings of
      the proposed method are clarified and its performance evaluated in terms of
      dependence on underlying assumptions. METHODS: The original method raised a
      number of concerns and several alternatives have since been proposed, including a
      simple linear regression approach. In our proposed generalized estimating
      equation approach, we maintain the simplicity of the linear regression model but
      obtain inferences that are more robust to approximation of the
      variance/covariance structure and can accommodate linkage disequilibrium.
      RESULTS: We affirm that, in principle, it is possible to determine that a
      'candidate' individual has participated in a study, given a subset of aggregate
      statistics from that study. However, the methods depend critically on a number of
      key factors including: the ancestry of participants in the study; the absolute
      and relative numbers of cases and controls; and the number of single nucleotide
      polymorphisms. CONCLUSIONS: Simple guidelines for publication that are based on a
      single criterion are therefore unlikely to suffice. In particular, 'directed'
      summary statistics should not be posted openly on the web but could be protected
      by an internet-based access check as proposed by the P3G_Consortium et al.
      (Public access to genome-wide data: five views on balancing research with privacy
      and protection. PLoS Genet 2009;5:e1000665).

PMID- 22158672
TI  - Demonstrating bias and improved inference for stoves' health benefits.
AB  - BACKGROUND: Many studies associate health risks with household air pollution from
      biomass fuels and stoves. Evaluations of stove improvements can suffer from bias
      because they rarely address health-relevant differences between the households
      who get improvements and those who do not. METHODS: We demonstrate both the
      potential for bias and an option for improved stove inference by applying to
      household air pollution a technique used elsewhere in epidemiology, propensity
      score matching (PSM), based on a stoves-and-health survey for China (15 counties,
      3500 households). RESULTS: Health-relevant factors (age, wealth, kitchen
      ventilation) do in fact differ considerably between the households with stove
      improvements and those without. We study the resulting bias in estimates of
      cleaner-stove impacts using a self-reported Physical Component Summary (PCS).
      Typical stoves-literature regressions with little control for non-stove factors
      suggest no benefits from a cleaner-fuel stove relative to a traditional biomass
      stove. Yet increasing controls raises the impact estimates. Our PSM estimates
      address the differences in health-relevant factors using 'apples to apples'
      comparisons between those with improved stoves and 'similar' households. This
      generates higher estimates of clean-stove benefits, which are on the order of one
      half the standard deviation of the PCS outcome. CONCLUSIONS: Our data demonstrate
      the potential importance of bias in household air pollution studies. This results
      from failure to address the possibility that those receiving improved stoves are
      themselves prone to better or worse health outcomes. It suggests the value of
      data collection and of study design for cookstove interventions and, more
      generally, for policy interventions within many health outcomes.

PMID- 22158674
TI  - IARC's plea for traditional 'expert' working groups--a recipe for problems?

PMID- 22158675
TI  - Arabidopsis Deficient in Cutin Ferulate encodes a transferase required for
      feruloylation of omega-hydroxy fatty acids in cutin polyester.
AB  - The cuticle is a complex aliphatic polymeric layer connected to the cell wall and
      covers surfaces of all aerial plant organs. The cuticle prevents nonstomatal
      water loss, regulates gas exchange, and acts as a barrier against pathogen
      infection. The cuticle is synthesized by epidermal cells and predominantly
      consists of an aliphatic polymer matrix (cutin) and intracuticular and
      epicuticular waxes. Cutin monomers are primarily C(16) and C(18) unsubstituted,
      omega-hydroxy, and alpha,omega-dicarboxylic fatty acids. Phenolics such as
      ferulate and p-coumarate esters also contribute to a minor extent to the cutin
      polymer. Here, we present the characterization of a novel acyl-coenzyme A (CoA)
      dependent acyl-transferase that is encoded by a gene designated Deficient in
      Cutin Ferulate (DCF). The DCF protein is responsible for the feruloylation of
      omega-hydroxy fatty acids incorporated into the cutin polymer of aerial
      Arabidopsis (Arabidopsis thaliana) organs. The enzyme specifically transfers
      hydroxycinnamic acids using omega-hydroxy fatty acids as acyl acceptors and
      hydroxycinnamoyl-CoAs, preferentially feruloyl-CoA and sinapoyl-CoA, as acyl
      donors in vitro. Arabidopsis mutant lines carrying DCF loss-of-function alleles
      are devoid of rosette leaf cutin ferulate and exhibit a 50% reduction in ferulic
      acid content in stem insoluble residues. DCF is specifically expressed in the
      epidermis throughout all green Arabidopsis organs. The DCF protein localizes to
      the cytosol, suggesting that the feruloylation of cutin monomers takes place in
      the cytoplasm.

PMID- 22158673
TI  - China Kadoorie Biobank of 0.5 million people: survey methods, baseline
      characteristics and long-term follow-up.
AB  - BACKGROUND: Large blood-based prospective studies can provide reliable assessment
      of the complex interplay of lifestyle, environmental and genetic factors as
      determinants of chronic disease. METHODS: The baseline survey of the China
      Kadoorie Biobank took place during 2004-08 in 10 geographically defined regions,
      with collection of questionnaire data, physical measurements and blood samples.
      Subsequently, a re-survey of 25,000 randomly selected participants was done (80%
      responded) using the same methods as in the baseline. All participants are being
      followed for cause-specific mortality and morbidity, and for any hospital
      admission through linkages with registries and health insurance (HI) databases.
      RESULTS: Overall, 512,891 adults aged 30-79 years were recruited, including 41%
      men, 56% from rural areas and mean age was 52 years. The prevalence of ever
      regular smoking was 74% in men and 3% in women. The mean blood pressure was
      132/79 mmHg in men and 130/77 mmHg in women. The mean body mass index (BMI) was
      23.4 kg/m(2) in men and 23.8 kg/m(2) in women, with only 4% being obese (>30
      kg/m(2)), and 3.2% being diabetic. Blood collection was successful in 99.98% and
      the mean delay from sample collection to processing was 10.6 h. For each of the
      main baseline variables, there is good reproducibility but large heterogeneity by
      age, sex and study area. By 1 January 2011, over 10,000 deaths had been recorded,
      with 91% of surviving participants already linked to HI databases. CONCLUSION:
      This established large biobank will be a rich and powerful resource for
      investigating genetic and non-genetic causes of many common chronic diseases in
      the Chinese population.

PMID- 22158676
TI  - Differential expression of biphenyl synthase gene family members in fire-blight
      infected apple 'Holsteiner Cox'.
AB  - Fire blight, caused by the bacterium Erwinia amylovora, is a devastating disease
      of apple (Malus * domestica). The phytoalexins of apple are biphenyls and
      dibenzofurans, whose carbon skeleton is formed by biphenyl synthase (BIS), a type
      III polyketide synthase. In the recently published genome sequence of apple
      'Golden Delicious', nine BIS genes and four BIS gene fragments were detected. The
      nine genes fall into four subfamilies, referred to as MdBIS1 to MdBIS4. In a
      phylogenetic tree, the BIS amino acid sequences from apple and Sorbus aucuparia
      formed an individual cluster within the clade of the functionally diverse type
      III polyketide synthases. cDNAs encoding MdBIS1 to MdBIS4 were cloned from fire
      blight-infected shoots of apple 'Holsteiner Cox,' heterologously expressed in
      Escherichia coli, and functionally analyzed. Benzoyl-coenzyme A and salicoyl
      coenzyme A were the preferred starter substrates. In response to inoculation with
      E. amylovora, the BIS3 gene was expressed in stems of cv Holsteiner Cox, with
      highest transcript levels in the transition zone between necrotic and healthy
      tissues. The transition zone was the accumulation site of biphenyl and
      dibenzofuran phytoalexins. Leaves contained transcripts for BIS2 but failed to
      form immunodetectable amounts of BIS protein. In cell cultures of apple 'Cox
      Orange,' expression of the BIS1 to BIS3 genes was observed after the addition of
      an autoclaved E. amylovora suspension. Using immunofluorescence localization
      under a confocal laser-scanning microscope, the BIS3 protein in the transition
      zone of stems was detected in the parenchyma of the bark. Dot-shaped
      immunofluorescence was confined to the junctions between neighboring cortical
      parenchyma cells.

PMID- 22158678
TI  - Pyrophosphate-dependent fructose-6-phosphate 1-phosphotransferase induction and
      attenuation of Hsp gene expression during endosperm modification in quality
      protein maize.
AB  - Quality Protein Maize (QPM) is a hard-endosperm version of the high-lysine
      opaque2 (o2) maize (Zea mays) mutant, but the genes involved in modification of
      the soft o2 endosperm are largely unknown. Pyrophosphate-dependent fructose-6
      phosphate 1-phosphotransferase (PFP) catalyzes the ATP-independent conversion of
      fructose-6-phosphate to fructose-1,6-bisphosphate in glycolysis. We found a large
      increase in transcript and protein levels of the alpha-regulatory subunit of PFP
      (PFPalpha) in QPM endosperm. In vitro enzyme assays showed a significant increase
      in forward PFP activity in developing endosperm extracts of QPM relative to the
      wild type and o2. An expressed retrogene version of PFPalpha of unknown function
      that was not up-regulated in QPM was also identified. The elevated expression
      levels of a number of ATP-requiring heat shock proteins (Hsps) in o2 endosperm
      are ameliorated in QPM. PFPalpha is also coinduced with Hsps in maize roots in
      response to heat, cold, and the unfolded protein response stresses. We propose
      that reduced ATP availability resulting from the generalized Hsp response in
      addition to the reduction of pyruvate, orthophosphate dikinase activity in o2
      endosperm is compensated in part by increased PFP activity in QPM.

PMID- 22158679
TI  - Hypotension as a Risk Factor for Acute Kidney Injury in ICU Patients.
AB  - In the context of critical illness, hypotension may be associated with acute
      kidney injury (AKI). Using the MIMIC II database, we studied the risk of AKI in
      ICU patients as a function of both the severity and duration of hypotension.
      Multivariate logistical regression was performed to find correlations between
      hypotension and AKI. Minimum mean arterial blood pressure (MAP) and the amount of
      time MAP was below a range of hypotension thresholds in a target 48-hour window
      (prior to AKI onset) were used as primary predictive variables in the
      multivariate model. Our results indicate that the risk of AKI was related to the
      severity of hypotension with an odds ratio (OR) of 1.03, 95% CI 1.02-1.04 (p <
      0.0001) per 1 mmHg decrease in minimum MAP >= 80 mmHg. For each additional hour
      MAP was less than 70, 60, 50 mmHg, the risk of AKI increased by 2% (OR 1.02, 95%
      CI 1.00-1.03, p = 0.0034), 5% (OR 1.05, 95% CI 1.02-1.08, p = 0.0028), and 22%
      (OR 1.22, 95% CI 1.04-1.43, p = 0.0122) respectively.

PMID- 22158677
TI  - Regulation of high-affinity nitrate uptake in roots of Arabidopsis depends
      predominantly on posttranscriptional control of the NRT2.1/NAR2.1 transport
      system.
AB  - In Arabidopsis (Arabidopsis thaliana), the NRT2.1 gene codes for the main
      component of the root nitrate (NO(3)(-)) high-affinity transport system (HATS).
      Due to the strong correlation generally found between high-affinity root NO(3)(-)
      influx and NRT2.1 mRNA level, it has been postulated that transcriptional
      regulation of NRT2.1 is a key mechanism for modulation of the HATS activity.
      However, this hypothesis has never been demonstrated, and is challenged by
      studies suggesting the occurrence of posttranscriptional regulation at the NRT2.1
      protein level. To unambiguously clarify the respective roles of transcriptional
      and posttranscriptional regulations of NRT2.1, we generated transgenic lines
      expressing a functional 35S::NRT2.1 transgene in an atnrt2.1 mutant background.
      Despite a high and constitutive NRT2.1 transcript accumulation in the roots, the
      HATS activity was still down-regulated in the 35S::NRT2.1 transformants in
      response to repressive nitrogen or dark treatments that strongly reduce NRT2.1
      transcription and NO(3)(-) HATS activity in the wild type. In some treatments,
      this was associated with a decline of NRT2.1 protein abundance, indicating
      posttranscriptional regulation of NRT2.1. However, in other instances, NRT2.1
      protein level remained constant. Changes in abundance of NAR2.1, a partner
      protein of NRT2.1, closely followed those of NRT2.1, and thus could not explain
      the close-to-normal regulation of the HATS in the 35S::NRT2.1 transformants. Even
      if in certain conditions the transcriptional regulation of NRT2.1 contributes to
      a limited extent to the control of the HATS, we conclude from this study that
      posttranscriptional regulation of NRT2.1 and/or NAR2.1 plays a predominant role
      in the control of the NO(3)(-) HATS in Arabidopsis.

PMID- 22158680
TI  - Randomized trial of type 1 and type 3 oral monovalent poliovirus vaccines in
      newborns in Africa.
AB  - BACKGROUND: The Global Polio Eradication Initiative aims to eradicate wild
      poliovirus by the end of 2012. Therefore, more-immunogenic polio vaccines,
      including monovalent oral poliovirus vaccines (mOPVs), are needed for
      supplemental immunization activities. This trial assessed the immunogenicity of
      monovalent types 1 and 3, compared with that of trivalent oral poliovirus vaccine
      (tOPV), in South Africa. METHODS: We conducted a blinded, randomized, 4-arm
      controlled trial comparing the immunogenicity of a single dose of mOPV1 (from 2
      manufacturers) and mOPV3 (from 1 manufacturer), given at birth, with the
      immunogenicity of tOPV. RESULTS: Eight hundred newborns were enrolled; 762 (95%)
      were included in the analysis. At 30 days after vaccine administration,
      seroconversion to poliovirus type 1 was 73.4% and 76.4% in the 2 mOPV1 arms,
      compared with 39.1% in the tOPV arm (P < .0000001), and seroconversion to
      poliovirus type 3 was 58.0% in the mOPV3 arm, compared with 21.2% in the tOPV arm
      (P < .0000001). The vaccines were well tolerated, and no adverse events were
      attributed to trial interventions. CONCLUSION: A dose of mOPV1 or mOPV3 at birth
      was superior to that of tOPV in inducing type-specific seroconversion in this sub
      Saharan African population. Our results support continued use of mOPVs in
      supplemental immunization activities in countries where poliovirus types 1 or 3
      circulate. Clinical Trials Registration. ISRCTN18107202.

PMID- 22158681
TI  - The final phase of polio eradication: new vaccines and complex choices.

PMID- 22158682
TI  - Safety and immunogenicity of inactivated poliovirus vaccine made from Sabin
      strains: a phase II, randomized, positive-controlled trial.
AB  - BACKGROUND: The production of Sabin inactivated poliovirus vaccine (IPV) can
      reduce biosafety requirements in the posteradication/post-oral poliovirus vaccine
      (OPV) era. We conducted a phase II, randomized, positive-controlled trial to
      assess the safety and immunogenicity of Sabin IPV. METHODS: The test groups (A,
      B, and C) received 3 doses of high, middle, and low D antigen (D Ag) of Sabin IPV
      at ages 2, 3, and 4 months, respectively. Infants in 2 control groups, group D
      and group E, received 3 doses of trivalent OPV and conventional IPV (cIPV),
      respectively, on the same schedule as that of groups A, B, and C. Serum samples
      were collected before and 30 days after the administration of the third dose.
      RESULTS: In total, 500 infants were randomly assigned to 5 groups, and 449
      infants completed the vaccine series. No serious adverse events were associated
      with vaccinations. After 3 doses, the seroconversion rates in groups A, B, C, D,
      and E were 100%, 97.8%, 96.6%, 100%, and 90.1%, respectively, for type 1
      poliovirus; 97.7%, 95.7%, 78.7%, 100%, and 90.1%, respectively, for type 2; and
      98.8%, 98.9%, 93.3%, 100%, and 97.8%, respectively, for type 3. CONCLUSIONS:
      Sabin IPV has good safety characteristics. The seroconversion rates for type 1
      poliovirus (most appropriate concentration, 15 D Ag units [DU]), type 2 (32 DU),
      and type 3 (45 DU) Sabin IPV were similar to those of the OPV and cIPV control
      groups. CLINICAL TRIALS REGISTRATION: NCT01056705.

PMID- 22158683
TI  - Ring cleavage reactions of methyl alpha-D-allopyranoside derivatives with
      phenylboron dichloride and triethylsilane.
AB  - In the course of our studies on the regioselective carbon-oxygen bond cleavage of
      the benzylidene acetal group of hexopyranosides with a reducing agent, we found
      that a combination of a Lewis acid and a reducing agent triggered a ring-opening
      reaction of the pyranose ring of methyl alpha-D-allopyranosides. The formation of
      an acyclic boronate ester by the attachment of a hydride ion at C-1 indicated
      that the unexpected endocyclic cleavage of the bond between the anomeric carbon
      atom and the pyranose ring oxygen atom proceeded via an oxacarbenium ion
      intermediate produced by the chelation between O5/O6 of the pyranoside and the
      Lewis acid, followed by nucleophile substitution with a hydride ion at C1.

PMID- 22158684
TI  - Antimony(V) and bismuth(V) complexes of lapachol: synthesis, crystal structure
      and cytotoxic activity.
AB  - Antimony(V) and bismuth(V) complexes of lapachol have been synthesized by the
      reaction of Ph3SbCl2 or Ph3BiCl2 with lapachol (Lp) and characterized by several
      physicochemical techniques such as IR, and NMR spectroscopy and X-ray
      crystallography. The compounds contain six-coordinated antimony and bismuth
      atoms. The antimony(V) complex is a monomeric derivative, (Lp)(Ph3Sb)OH, and the
      bismuth(V) complex is a dinuclear compound bridged by an oxygen atom,
      (Lp)2(Ph3Bi)2O. Both compounds inhibited the growth of a chronic myelogenous
      leukemia cell line and the complex of Bi(V) was about five times more active than
      free lapachol. This work provides a rare example of an organo-Bi(V) complex
      showing significant cytotoxic activity.

PMID- 22158685
TI  - Immunomodulatory activity of polysaccharide-protein complex of longan (Dimocarpus
      longan Lour.) pulp.
AB  - The immunomodulatory function of longan pulp polysaccharide-protein complex (LP3)
      was investigated in immunosuppressed mice models. Compared with the model
      control, peroral administration of 100 mgkg-1d-1 LP3 could significantly
      increase/enhance antibody production against chicken red blood cell (CRBC),
      concanavalin A (ConA)-induced splenocyte proliferation, macrophage phagocytosis,
      NK cell cytotoxicity against YAC-1 lymphoma cell, and interferon-gamma (INF
      gamma) and interleukin-2 (IL-2) secretion in serum (P < 0.05). The
      immunomodulatory effects, except for those on splenocytes and macrophages (P >
      0.05), were also observed in mice administered with 50 or 200 mgkg-1d-1 LP3 (P <
      0.05). The beneficial effects of 50-200 mgkg-1d-1 LP3 were comparable to those of
      50 mgkg-1d-1 ganoderan. The strong immunomodulatory activity of LP3 confirmed its
      good potential as an immunotherapeutic adjuvant.

PMID- 22158686
TI  - Hybrid charged heterometallic Pt-Ir complexes: tailoring excited states by taking
      the best of both worlds.
AB  - The C=C-linkage of Pt(PR(3))(2)(C=CAr)(2) with (C^N)(2)Ir(N^N)(+) (C^N = 2
      phenylpyridine; N^N = bipyridyl) leads to hetero-bi- and trimetallic species
      exhibiting photophysical properties reminiscent of both [Pt]- and [Ir]-containing
      moieties through the generation of a [Pt] -> [Ir] charge transfer excited state.

PMID- 22158689
TI  - Generalizability analyses of NBDE Part II.
AB  - This research applied generalizability theory to assess the effect of varying the
      number of cases and items nested within cases on generalizability of scores on
      Part II of the National Board Dental Examinations (NBDE Part II). In this
      research, sources of error were defined. Measurement conditions were classified.
      Error variances and generalizability coefficients for different conditions were
      computed. The data analyzed were the item responses of 1,535 candidates enrolled
      in accredited dental education programs who all took the same test form in 2007.
      Results showed that using more cases of fewer items might lead to a greater
      increase in generalizability than using more items per case. Other practical
      considerations such as time and cost constraints must be taken into account when
      applying the results of this research in other testing situations.

PMID- 22158688
TI  - Defining physicians' readiness to screen and manage intimate partner violence in
      Greek primary care settings.
AB  - The current article aims to translate the PREMIS (Physician Readiness to Manage
      Intimate Partner Violence) survey into the Greek language and test its validity
      and reliability in a sample of primary care physicians. The validation study was
      conducted in 2010 and involved all the general practitioners serving two adjacent
      prefectures of Greece (n = 80). Maximum-likelihood factor analysis (MLF) was used
      to extract key survey factors. The instrument was further assessed for the
      following psychometric properties: (a) scale reliability, (b) item-specific
      reliability, (c) test-retest reliability, (d) scale construct validity, and (e)
      internal predictive validity. The MLF analysis of 23 opinion items revealed a
      seven-factor solution (preparation, constraint, workplace issues, screening, self
      efficacy, alcohol/drugs, victim understanding), which was statistically sound (p
      = .293). Most of the newly derived scales displayed satisfactory internal
      consistency (alpha >= .60), high item-specific reliability, strong construct, and
      internal predictive validity (F = 2.82; p = .004), and high repeatability when
      retested with 20 individuals (intraclass correlation coefficient [ICC] > .70).
      The tool was found appropriate to facilitate the identification of competence
      deficits and the evaluation of training initiatives.

PMID- 22158690
TI  - A comparison of empirical ranking methods of frequency and severity ratings of
      clinical presentations.
AB  - This study compares five methods of ranking Likert ratings on frequency and
      severity scales. Data were drawn from an international online survey conducted as
      part of a practice analysis with 91 diplomates of the American Chiropractic Board
      of Radiology. A total of 129 clinical presentations had been rated on two scales.
      The frequency scale specifies how often each condition is seen in practice from 1
      (never) to 5 (daily). The severity scale indicates how severe each condition is
      to the patient from 1 (no risk) to 5 (severe risk). These ratings were used in
      five methods of ranking to identify the 10 most important conditions reported by
      chiropractic radiologists. The similarity of ranks across the five methods was
      then analyzed with Spearman's rank correlations. The results of the study
      indicate that the Rasch model provides the most precise results about the
      importance of conditions seen in practice.

PMID- 22158691
TI  - Contrasting case definitions for chronic fatigue syndrome, Myalgic
      Encephalomyelitis/chronic fatigue syndrome and myalgic encephalomyelitis.
AB  - This article uses data from patients recruited using the 1994 case definition of
      chronic fatigue syndrome (CFS) to contrast those meeting criteria for the Myalgic
      Encephalomyelitis/chronic fatigue syndrome (ME/CFS) Canadian case definition with
      those that did not meet these criteria. The study also contrasts those meeting
      criteria for Myalgic Encephalomyelitis (ME) based on criteria from Ramsay and
      other theorists with those that did not meet the ME criteria. The ME/CFS case
      definition criteria identified a subset of patients with more functional
      impairments and physical, mental, and cognitive problems than the subset not
      meeting these criteria. The ME subset had more functional impairments, and more
      severe physical and cognitive symptoms than the subset not meeting ME criteria.
      When applied to a population meeting the 1994 CFS case definition, both ME/CFS
      and ME criteria appear to select a more severe subset of patients.

PMID- 22158692
TI  - Towards a detailed in situ characterization of non-stationary electrocatalytic
      systems.
AB  - A complementary combination of cyclic voltammetry, impedance spectroscopy and
      quartz crystal microbalance techniques was used to: (i) control the assembly of a
      model electrocatalytic system consisting of monolayer and sub-monolayer amounts
      of Ag and Pb on a Au electrode, (ii) evaluate the system performance for the
      reduction of NO(3)(-) and (iii) study the disassembly of the electrocatalytic
      system to explore any changes which occurred during the assembly and/or catalytic
      stages. Physical models of the electrochemical interface (described in terms of
      equivalent electric circuits) at all stages are found to be considerably
      different but consistent with each other. Deposition of the Ag atomic layer on Au
      is accompanied by spontaneous surface alloying and specific adsorption of anions.
      In the following, deposition of the Pb atomic layer triggers further alloying in
      the Ag(ad)/Au layer while perchlorate-ions leave the surface. Approximately 1/3
      of the Pb atomic layer on Ag(ad)/Au was found to demonstrate the best activity
      towards nitrate reduction. The developed experimental approach shows promise for
      the in situ characterization and control of all the non-stationary stages which
      are usually of particular importance in electrocatalytic research.

PMID- 22158693
TI  - Ionic liquids and acid gas capture: water and oxygen as confounding factors.
AB  - Amines dissolved in ionic liquids react rapidly with SO(2) to produce new
      materials. Compounds related to the stepwise conversion of SO(2) to sulfite and
      sulfate salts have been isolated. Trapping SO(2) in the form of the sulfite anion
      does not change the oxidation state of sulfur and should maintain the
      reversibility of the capture system.

PMID- 22158695
TI  - Identification and quantification of EPA 16 priority polycyclic aromatic
      hydrocarbon pollutants by Maximum-Quantum NMR.
AB  - We demonstrate here that the recently introduced Maximum-Quantum NMR analytical
      strategy is apt for the identification and quantification of 16 polycyclic
      aromatic hydrocarbon (PAH) pollutants in a mixture and does not need prior
      separation. The accuracy of the procedure, the response of which is linear in
      concentration, was assessed and its feasibility was demonstrated down to a
      concentration of about 30 MUM.

PMID- 22158694
TI  - Regiospecific linear assembly of Pd nanocubes for hydrogen gas sensing.
AB  - Capillary force lithography was applied to generate large area polymer patterns.
      A "grafting to" approach was used on the patterns to induce linear assembly of Pd
      nanocubes through electrostatic interaction. Pd nanoarrays with high density were
      subjected to a hydrogen gas sensing test. We demonstrated a feasible method to
      build up a miniature hydrogen sensor using self-assembly with micrometre Pd
      nanoarrays.

PMID- 22158696
TI  - A resonance light scattering quenching system for studying DNA sequence
      recognition of actinomycin D.
AB  - The DNA sequence recognition study of DNA-targeted anticancer drugs is a
      theoretical basis for improving the selectivity of anticancer drugs. With the
      high synergy effect of cocoamidopropyl hydroxy sulfobetaine (HSB), a resonance
      light scattering (RLS) quenching system for DNA sequence recognition studies of
      actinomycin D (ACTD) was developed in this contribution. By the strategy, DNA
      sequence selectivity as well as the recognition mechanisms of ACTD was
      systematically investigated. The results suggested that ACTD had the selectivity
      to single-stranded DNA (ssDNA) with an equilibrium constant (K(RLS)) of 12.4 mmol
      mg(-1). Also it had a preference for Guanine and Cytosine bases with a K(RLS) of
      6.69 L mmol(-1). The selectivity mechanism between ACTD and DNA was also well
      discussed with the help of UV-Vis absorption spectroscopy. Compared with other
      methods, the RLS quenching system has the advantages of reliability and
      speediness, and it avoids complex modification processes and is a better bionic
      system for the above research. Results obtained from this work would supply a
      theoretical basis for improving anticancer activity and designing similar
      anticancer drugs.

PMID- 22158697
TI  - Talking openly: using '6D cards' to facilitate holistic, patient-led
      communication.
AB  - OBJECTIVE: The study investigates the effectiveness and acceptability of a
      communication tool (the '6D Cards') in facilitating holistic, patient-led
      communication in medical consultations. DESIGN: A between-subjects design was
      employed, whereby patients were randomly allocated to either use the '6D Cards'
      to initiate conversation or engage in the usual discussion processes. SETTING:
      The study was carried out in an outpatient gynaecology clinic at a National
      Health Service (NHS) public hospital in a small town. PARTICIPANTS: Seventy-one
      patients were given the '6D Cards' and 69 control patients had a normal
      consultation. All participants were females aged 18 years or older. Participants
      were consenting patients visiting the clinic during the 3-month data collection
      period and included both first time and known patients. INTERVENTION: The Cards
      contain 40 issues across 6 dimensions ('6D') of health and were designed in
      consultation with clinical staff. The aim of the '6D Cards' is to give patients
      the option of discussing broader aspects of their presenting problem. MAIN
      OUTCOME MEASURES: The primary outcome measures were the number and types of
      issues raised by all patients, with and without the use of the cards and a short
      acceptability questionnaire, which was completed by all patients following their
      consultations. RESULTS: /st> Patients using the cards raised significantly more
      issues than the control patients. Furthermore, patients raised overall no
      concerns about the acceptability of the cards. CONCLUSIONS: The '6D Cards' could
      be a useful communication tool to enable patients to raise general concerns and
      issues during their consultations.

PMID- 22158699
TI  - Swine to human transmission of reassortants of pandemic (H1N1) 2009 and endemic
      swine influenza viruses: Abstract.
AB  - To gain insight into the possible origin of a new reassortant influenza A virus
      between pandemic (H1N1) 2009 and endemic swine viruses that has jumped the
      species barrier and caused a few infections among humans in Indiana and
      Pennsylvania recently, we analyzed all full genome sequences related to this
      virus and report its evolutionary history, but failed to determine how the virus
      had emerged simultaneously in two geographically distinct areas.

PMID- 22158701
TI  - Using interviews to understand the assignment mechanism in a nonexperimental
      study: the case of eighth grade algebra.
AB  - Many inquiries regarding the causal effects of policies or programs are based on
      research designs where the treatment assignment process is unknown, and thus
      valid inferences depend on tenuous assumptions about the assignment mechanism.
      This article draws attention to the importance of understanding the assignment
      mechanism in policy and program evaluation studies, and illustrates how
      information collected through interviews can develop a richer understanding of
      the assignment mechanism. Focusing on the issue of student assignment to algebra
      in 8th grade, I show how a preliminary data collection effort aimed at
      understanding the assignment mechanism is particularly beneficial in multisite
      observational studies in education. The findings, based on ten interviews and
      administrative data from a large school district, draw attention to the often
      ignored heterogeneity in the assignment mechanism across schools. These findings
      likely extend beyond the current research project in question to related
      educational policy issues such as ability grouping, tracking, differential course
      taking, and curricular intensity, as well as other social programs in which the
      assignment mechanism can differ across sites.

PMID- 22158700
TI  - A CCCH-type zinc finger nucleic acid-binding protein quantitatively confers
      resistance against rice bacterial blight disease.
AB  - Bacterial blight is a devastating disease of rice (Oryza sativa) caused by
      Xanthomonas oryzae pv oryzae (Xoo). Zinc finger proteins harboring the motif with
      three conserved cysteine residues and one histidine residue (CCCH) belong to a
      large family. Although at least 67 CCCH-type zinc finger protein genes have been
      identified in the rice genome, their functions are poorly understood. Here, we
      report that one of the rice CCCH-type zinc finger proteins, C3H12, containing
      five typical CX(8)-CX(5)-CX(3)-H zinc finger motifs, is involved in the rice-Xoo
      interaction. Activation of C3H12 partially enhanced resistance to Xoo,
      accompanied by the accumulation of jasmonic acid (JA) and induced expression of
      JA signaling genes in rice. In contrast, knockout or suppression of C3H12
      resulted in partially increased susceptibility to Xoo, accompanied by decreased
      levels of JA and expression of JA signaling genes in rice. C3H12 colocalized with
      a minor disease resistance quantitative trait locus to Xoo, and the enhanced
      resistance of randomly chosen plants in the quantitative trait locus mapping
      population correlated with an increased expression level of C3H12. The C3H12
      protein localized in the nucleus and possessed nucleic acid-binding activity in
      vitro. These results suggest that C3H12, as a nucleic acid-binding protein,
      positively and quantitatively regulates rice resistance to Xoo and that its
      function is likely associated with the JA-dependent pathway.

PMID- 22158703
TI  - Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia in
      HIV/HCV-coinfected patients with all HCV genotypes.
AB  - BACKGROUND: A recent genome-wide association study reported a strong association
      with a single-nucleotide polymorphism (SNP) in the inosine triphosphate (ITPA)
      gene and hemolytic anemia in patients infected with hepatitis C virus (HCV)
      receiving pegylated interferon and ribavirin. We investigate these polymorphisms
      in a cohort of human immunodeficiency virus (HIV)/HCV-coinfected patients.
      METHODS: DNA was available for 161 patients with validated outcomes. We analyzed
      the association between the variants and week 4 hemoglobin reduction. Anemia over
      the course of therapy, ribavirin (RBV) dose reduction, serum RBV level, and rapid
      virological response (RVR) and sustained virological response (SVR) were also
      investigated. Using a candidate gene approach, ITPA variants rs1127354 and
      rs7270101 were tested using the ABI TaqMan kit. Multivariable models were used to
      identify predictors of anemia. RESULTS: A significant minority (33%) of patients
      were predicted to have reduced ITPase activity. The minor allele of each variant
      was associated with protection against week 4 anemia. In multivariable models
      only the genetic variants, creatinine, and zidovudine exposure remained
      significant. ITPase deficiency was not associated with RBV-dose reduction, RVR,
      or SVR. CONCLUSIONS: This study confirms that polymorphisms in the ITPA gene are
      associated with protection from RBV-induced anemia in HIV/HCV-coinfected patients
      but not improved clinical outcomes.

PMID- 22158704
TI  - Local innate immune responses and influenza virus transmission and virulence in
      ferrets.
AB  - Host innate immunity is the first line of defense against invading pathogens,
      including influenza viruses. Ferrets are well recognized as the best model of
      influenza virus pathogenesis and transmission, but little is known about the
      innate immune response of ferrets after infection with this virus. The goal of
      this study was to investigate the contribution of localized host responses to
      influenza virus pathogenicity and transmissibility in this model by measuring the
      level of messenger RNA expression of 12 cytokines and chemokines in the upper and
      lower respiratory tracts of ferrets infected with H5N1, H1N1, or H3N2 influenza
      viruses that exhibit diverse virulence and transmissibility in ferrets. We found
      a strong temporal correlation between inflammatory mediators and the kinetics and
      frequency of transmission, clinical signs associated with transmission, peak
      virus shedding, and virulence. Our findings point to a link between localized
      innate immunity and influenza virus transmission and disease progression.

PMID- 22158705
TI  - Synthesizing amphiphilic block copolymers through macromolecular azo-coupling
      reaction.
AB  - This communication reports a new approach to synthesize amphiphilic block
      copolymers. The copolymers with well-defined structures were synthesized by
      macromolecular azo-coupling reaction between the diazonium salt of aniline
      functionalized PEG and the polymeric blocks with a terminal suitable for the azo
      coupling reaction.

PMID- 22158706
TI  - Label-free aptamer-based electrochemical impedance biosensor for 17beta
      estradiol.
AB  - A novel aptamer-based label-free electrochemical impedance spectroscopy biosensor
      for 17beta-estradiol has been fabricated. The aptamers were firstly immobilized
      on the gold electrode through Au-S interaction; the aptamer probe was then bound
      with the addition of 17beta-estradiol to form the estradiol/aptamer complex on
      the electrode surface. This leads to a significantly larger interfacial electron
      transfer resistance than that without the addition of 17beta-estradiol. The
      change in the resistance had a linear relationship with 17beta-estradiol
      concentration in the range of 1.0 * 10(-8) to 1.0 * 10(-11) mol L(-1), with a
      detection limit of 2.0 * 10(-12) mol L(-1). The biosensor showed high selectivity
      to 17beta-estradiol and good stability. The designed biosensor has been applied
      to detect 17beta-estradiol in human urine with satisfactory results.

PMID- 22158707
TI  - Thymosin beta 4 is dispensable for murine cardiac development and function.
AB  - RATIONALE: Thymosin beta 4 (Tbeta4) is a 43-amino acid factor encoded by an X
      linked gene. Recent studies have suggested that Tbeta4 is a key factor in cardiac
      development, growth, disease, epicardial integrity, and blood vessel formation.
      Cardiac-specific short hairpin (sh)RNA knockdown of tbeta4 has been reported to
      result in embryonic lethality at E14.5-16.5, with severe cardiac and angiogenic
      defects. However, this shRNA tbeta4-knockdown model did not completely abrogate
      Tbeta4 expression. To completely ablate Tbeta4 and to rule out the possibility of
      off-target effects associated with shRNA gene silencing, further studies of
      global or cardiac-specific knockouts are critical. OBJECTIVE: We examined the
      role of Tbeta4 in developing and adult heart through global and cardiac specific
      tbeta4-knockout mouse models. METHODS AND RESULTS: Global tbeta4-knockout mice
      were born at mendelian ratios and exhibited normal heart and blood vessel
      formation. Furthermore, in adult global tbeta4-knockout mice, cardiac function,
      capillary density, expression of key cardiac fetal and angiogenic genes,
      epicardial marker expression, and extracellular matrix deposition were
      indistinguishable from that of controls. Tissue-specific tbeta4-deficient mice,
      generated by crossing tbeta4-floxed mice to Nkx2.5-Cre and alphaMHC-Cre, were
      also found to have no phenotype. CONCLUSIONS: We conclude that Tbeta4 is
      dispensable for embryonic viability, heart development, coronary vessel
      development, and adult myocardial function.

PMID- 22158708
TI  - Polycomb repressive complex 2 regulates normal development of the mouse heart.
AB  - RATIONALE: Epigenetic marks are crucial for organogenesis, but their role in
      heart development is poorly understood. Polycomb repressive complex 2 (PRC2)
      trimethylates histone H3 at lysine 27, which establishes H3K27me3 repressive
      epigenetic marks that promote tissue-specific differentiation by silencing
      ectopic gene programs. OBJECTIVE: We studied the function of PRC2 in murine heart
      development using a tissue-restricted conditional inactivation strategy. METHODS
      AND RESULTS: Inactivation of the PRC2 subunit Ezh2 by Nkx2-5(Cre) (Ezh2(NK))
      caused lethal congenital heart malformations, namely, compact myocardial
      hypoplasia, hypertrabeculation, and ventricular septal defect. Candidate and
      genome-wide RNA expression profiling and chromatin immunoprecipitation analyses
      of Ezh2(NK) heart identified genes directly repressed by EZH2. Among these were
      the potent cell cycle inhibitors Ink4a/b (inhibitors of cyclin-dependent kinase 4
      A and B), the upregulation of which was associated with decreased cardiomyocyte
      proliferation in Ezh2(NK). EZH2-repressed genes were enriched for transcriptional
      regulators of noncardiomyocyte expression programs such as Pax6, Isl1, and Six1.
      EZH2 was also required for proper spatiotemporal regulation of cardiac gene
      expression, because Hcn4, Mlc2a, and Bmp10 were inappropriately upregulated in
      ventricular RNA. PRC2 was also required later in heart development, as indicated
      by cardiomyocyte-restricted TNT-Cre inactivation of the PRC2 subunit Eed.
      However, Ezh2 inactivation by TNT-Cre did not cause an overt phenotype, likely
      because of functional redundancy with Ezh1. Thus, early Ezh2 inactivation by Nk2
      5(Cre) caused later disruption of cardiomyocyte gene expression and heart
      development. CONCLUSIONS: Our study reveals a previously undescribed role of EZH2
      in regulating heart formation and shows that perturbation of the epigenetic
      landscape early in cardiogenesis has sustained disruptive effects at later
      developmental stages.

PMID- 22158709
TI  - Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial
      fibrillation in FKBP12.6 knockout mice.
AB  - RATIONALE: Abnormal calcium release from sarcoplasmic reticulum (SR) is
      considered an important trigger of atrial fibrillation (AF). Whereas increased
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity has been proposed
      to contribute to SR leak and AF induction, downstream targets of CaMKII remain
      controversial. OBJECTIVE: To test the hypothesis that inhibition of CaMKII
      phosphorylated type-2 ryanodine receptors (RyR2) prevents AF initiation in
      FKBP12.6-deficient (-/-) mice. METHODS AND RESULTS: Mice lacking RyR2-stabilizing
      subunit FKBP12.6 had a higher incidence of spontaneous and pacing-induced AF
      compared with wild-type mice. Atrial myocytes from FKBP12.6-/- mice exhibited
      spontaneous Ca(2+) waves (SCaWs) leading to Na(+)/Ca(2+)-exchanger activation and
      delayed afterdepolarizations (DADs). Mutation S2814A in RyR2, which inhibits
      CaMKII phosphorylation, reduced Ca(2+) spark frequency, SR Ca(2+) leak, and DADs
      in atrial myocytes from FKBP12.6-/-:S2814A mice compared with FKBP12.6-/- mice.
      Moreover, FKBP12.6-/-:S2814A mice exhibited a reduced susceptibility to inducible
      AF, whereas FKBP12.6-/-:S2808A mice were not protected from AF. CONCLUSIONS:
      FKBP12.6 mice exhibit AF caused by SR Ca(2+) leak, Na(+)/Ca(2+)-exchanger
      activation, and DADs, which promote triggered activity. Genetic inhibition of
      RyR2-S2814 phosphorylation prevents AF induction in FKBP12.6-/- mice by
      suppressing SR Ca(2+) leak and DADs. These results suggest suppression of RyR2
      S2814 phosphorylation as a potential anti-AF therapeutic target.

PMID- 22158710
TI  - H2O2-induced dilation in human coronary arterioles: role of protein kinase G
      dimerization and large-conductance Ca2+-activated K+ channel activation.
AB  - RATIONALE: Hydrogen peroxide (H(2)O(2)) serves as a key endothelium-derived
      hyperpolarizing factor mediating flow-induced dilation in human coronary
      arterioles (HCAs). The precise mechanisms by which H(2)O(2) elicits smooth muscle
      hyperpolarization are not well understood. An important mode of action of
      H(2)O(2) involves the oxidation of cysteine residues in its target proteins,
      including protein kinase G (PKG)-Ialpha, thereby modulating their activities.
      OBJECTIVE: Here we hypothesize that H(2)O(2) dilates HCAs through direct
      oxidation and activation of PKG-Ialpha leading to the opening of the large
      conductance Ca(2+)-activated K(+) (BK(Ca)) channel and subsequent smooth muscle
      hyperpolarization. METHODS AND RESULTS: Flow and H(2)O(2) induced pressure
      gradient/concentration-dependent vasodilation in isolated endothelium-intact and 
      denuded HCAs, respectively. The dilation was largely abolished by iberiotoxin, a
      BK(Ca) channel blocker. The PKG inhibitor Rp-8-Br-PET-cGMP also markedly
      inhibited flow- and H(2)O(2)-induced dilation, whereas the soluble guanylate
      cyclase inhibitor ODQ had no effect. Treatment of coronary smooth muscle cells
      (SMCs) with H(2)O(2) elicited dose-dependent, reversible dimerization of PKG
      Ialpha, and induced its translocation to the plasma membrane. Patch-clamp
      analysis identified a paxilline-sensitive single-channel K(+) current with a
      unitary conductance of 246-pS in freshly isolated coronary SMCs. Addition of
      H(2)O(2) into the bath solution significantly increased the probability of BK(Ca)
      single-channel openings recorded from cell-attached patches, an effect that was
      blocked by the PKG-Ialpha inhibitor DT-2. H(2)O(2) exhibited an attenuated
      stimulatory effect on BK(Ca) channel open probability in inside-out membrane
      patches. CONCLUSIONS: H(2)O(2) dilates HCAs through a novel mechanism involving
      protein dimerization and activation of PKG-Ialpha and subsequent opening of
      smooth muscle BK(Ca) channels.

PMID- 22158711
TI  - Posttranslational modifications of proteins in the pathobiology of medically
      relevant fungi.
AB  - Posttranslational modifications of proteins drive a wide variety of cellular
      processes in eukaryotes, regulating cell growth and division as well as adaptive
      and developmental processes. With regard to the fungal kingdom, most information
      about posttranslational modifications has been generated through studies of the
      model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, where, for
      example, the roles of protein phosphorylation, glycosylation, acetylation,
      ubiquitination, sumoylation, and neddylation have been dissected. More recently,
      information has begun to emerge for the medically important fungal pathogens
      Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans,
      highlighting the relevance of posttranslational modifications for virulence. We
      review the available literature on protein modifications in fungal pathogens,
      focusing in particular upon the reversible peptide modifications sumoylation,
      ubiquitination, and neddylation.

PMID- 22158712
TI  - The state of research for AIDS-associated opportunistic infections and the
      importance of sustaining smaller research communities.

PMID- 22158713
TI  - Enigmatic presence of mitochondrial complex I in Trypanosoma brucei bloodstream
      forms.
AB  - The presence of mitochondrial respiratory complex I in the pathogenic bloodstream
      stages of Trypanosoma brucei has been vigorously debated: increased expression of
      mitochondrially encoded functional complex I mRNAs is countered by low levels of
      enzymatic activity that show marginal inhibition by the specific inhibitor
      rotenone. We now show that epitope-tagged versions of multiple complex I subunits
      assemble into alpha and beta subcomplexes in the bloodstream stage and that these
      subcomplexes require the mitochondrial genome for their assembly. Despite the
      presence of these large (740- and 855-kDa) multisubunit complexes, the electron
      transport activity of complex I is not essential under experimental conditions
      since null mutants of two core genes (NUBM and NUKM) showed no growth defect in
      vitro or in mouse infection. Furthermore, the null mutants showed no decrease in
      NADH:ubiquinone oxidoreductase activity, suggesting that the observed activity is
      not contributed by complex I. This work conclusively shows that despite the
      synthesis and assembly of subunit proteins, the enzymatic function of the largest
      respiratory complex is neither significant nor important in the bloodstream
      stage. This situation appears to be in striking contrast to that for the other
      respiratory complexes in this parasite, where physical presence in a life-cycle
      stage always indicates functional significance.

PMID- 22158715
TI  - Addressing diffuse glioma as a systemic brain disease with single-cell analysis.
AB  - OBJECTIVE: To analyze infiltration patterns of IDH1 mutant diffuse gliomas into
      the brain by identification of single tumor cells applying an antibody specific
      to mutant IDH1 R132H protein. DESIGN: Immunohistochemical analysis. SETTING:
      University hospital. PATIENTS: Whole-brain and hemisphere sections of 4 patients
      diagnosed with diffuse glioma. RESULTS: Tumor cells were identified in areas that
      appeared inconspicuous macroscopically and at histological analysis with respect
      to cellularity, cellular pleomorphism, or mitotic activity in all cases.
      CONCLUSION: Detection of single tumor cells throughout the brain demonstrates
      diffuse glioma to represent systemic brain disease.

PMID- 22158714
TI  - Resolving phenylalanine metabolism sheds light on natural synthesis of penicillin
      G in Penicillium chrysogenum.
AB  - The industrial production of penicillin G by Penicillium chrysogenum requires the
      supplementation of the growth medium with the side chain precursor phenylacetate.
      The growth of P. chrysogenum with phenylalanine as the sole nitrogen source
      resulted in the extracellular production of phenylacetate and penicillin G. To
      analyze this natural pathway for penicillin G production, chemostat cultures were
      switched to [U-(13)C]phenylalanine as the nitrogen source. The quantification and
      modeling of the dynamics of labeled metabolites indicated that phenylalanine was
      (i) incorporated in nascent protein, (ii) transaminated to phenylpyruvate and
      further converted by oxidation or by decarboxylation, and (iii) hydroxylated to
      tyrosine and subsequently metabolized via the homogentisate pathway. The
      involvement of the homogentisate pathway was supported by the comparative
      transcriptome analysis of P. chrysogenum cultures grown with phenylalanine and
      with (NH(4))(2)SO(4) as the nitrogen source. This transcriptome analysis also
      enabled the identification of two putative 2-oxo acid decarboxylase genes
      (Pc13g9300 and Pc18g01490). cDNAs of both genes were cloned and expressed in the
      2-oxo-acid-decarboxylase-free Saccharomyces cerevisiae strain CEN.PK711-7C (pdc1
      pdc5 pdc6Delta aro10Delta thi3Delta). The introduction of Pc13g09300 restored the
      growth of this S. cerevisiae mutant on glucose and phenylalanine, thereby
      demonstrating that Pc13g09300 encodes a dual-substrate pyruvate and
      phenylpyruvate decarboxylase, which plays a key role in an Ehrlich-type pathway
      for the production of phenylacetate in P. chrysogenum. These results provide a
      basis for the metabolic engineering of P. chrysogenum for the production of the
      penicillin G side chain precursor phenylacetate.

PMID- 22158716
TI  - Autoantibodies to lipoprotein-related protein 4 in patients with double
      seronegative myasthenia gravis.
AB  - OBJECTIVES: To determine whether patients with myasthenia gravis (MG) have serum
      antibodies to lipoprotein-related protein 4 (LRP4), a newly identified receptor
      for agrin that is essential for neuromuscular junction formation, and to
      establish whether such antibodies contribute to MG pathogenesis. DESIGN: Serum
      samples from patients with MG with known status of serum antibodies to the
      acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) and serum samples
      from control subjects (healthy individuals and individuals with other diseases)
      were tested for antibodies to LRP4. Serum samples with such antibodies were
      tested to determine whether they had the ability to inhibit 2 different functions
      of LRP4 at the neuromuscular junction. SETTING: Serum samples were collected at
      the Hellenic Pasteur Institute and Wayne State University. Samples were tested
      for LRP4 autoantibodies at Georgia Health Sciences University. Other
      immunoreactivities of the samples were tested at the Hellenic Pasteur Institute,
      Athens, Greece, or processed through University Laboratories of the Detroit
      Medical Center, Michigan. Patients  The study included 217 patients with MG, 76
      patients with other neurologic or psychiatric diseases, and 45 healthy control
      subjects. RESULTS: Anti-LRP4 antibodies were detected in 11 of 120 patients with
      MG without detectable anti-AChR or anti-MuSK antibodies (double seronegative) and
      in 1 of 36 patients without anti-AChR antibodies but with anti-MuSK antibodies,
      but they were not detected in any of the 61 patients with anti-AChR antibodies.
      No healthy control subjects and only 2 of the 76 control patients with neurologic
      disease had anti-LRP4 antibodies. Serum samples from patients with MG with anti
      LRP4 antibodies were able to inhibit the LRP4-agrin interaction and/or alter AChR
      clustering in muscle cells. CONCLUSIONS: Anti-LRP4 antibodies were detected in
      the serum of approximately 9.2% of patients with double-seronegative MG. This
      frequency is intermediate compared with 2 recent studies showing anti-LRP4
      antibodies in 2% and 50% of patients with double-seronegative MG from different
      geographic locations. Together, these observations indicate that LRP4 is another
      autoantigen in patients with MG, and anti-LRP4 autoantibodies may be pathogenic
      through different immunopathogenic processes.

PMID- 22158717
TI  - Antibodies to low density lipoprotein receptor-related protein 4 in seronegative
      myasthenia gravis.

PMID- 22158718
TI  - Use of acetazolamide in sulfonamide-allergic patients with neurologic
      channelopathies.
AB  - OBJECTIVE: To report the safe and successful use of the carbonic anhydrase
      inhibitor acetazolamide for treatment of patients with episodic ataxia and
      periodic paralysis who had been denied treatment because of a history of severe
      allergic reactions to antibiotic sulfonamides. DESIGN: Case reports. SETTING:
      University of Rochester Medical Center, Rochester, New York. PATIENTS: A 61-year
      old man with late-onset episodic ataxia, an 83-year-old woman with mutation
      positive Andersen-Tawil syndrome, and a 21-year-old woman with mutation-positive
      episodic ataxia 2, all of whom had a history of severe skin rash with the use of
      sulfonamides for treatment of infection. RESULTS: The 3 patients had been
      considered for carbonic anhydrase inhibitor treatment but a pharmacist had
      refused to fill a prescription for acetazolamide for 1 patient and the other 2
      patients were denied treatment because of the allergy history. All 3 patients
      were prescribed acetazolamide and had no adverse reaction. Two patients improved
      substantially and are continuing treatment. A review of the pharmacology
      literature suggests that cross-reactivity between antibiotic and nonantibiotic
      carbonic anhydrase inhibitors is unlikely. Moreover, a review of case reports
      does not suggest cross-reactivity. Previous reports in the ophthalmology
      literature also indicate that acetazolamide can be administered to patients with
      a history of antibiotic sulfonamide allergic reaction. CONCLUSIONS: These 3 cases
      confirm that the carbonic anhydrase inhibitor acetazolamide can be given to
      patients with a history of allergic skin rash with antibiotic sulfonamide.

PMID- 22158719
TI  - Molecular pathophysiology and disease-modifying therapies for spinal and bulbar
      muscular atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA), or Kennedy disease, is an adult-onset
      lower motor neuron disease characterized by slowly progressive muscle weakness
      and atrophy. The disease is caused by the expansion of a trinucleotide CAG repeat
      encoding a polyglutamine tract within the first exon of the androgen receptor
      (AR) gene. During the 2 decades since the discovery of the AR gene mutation in
      SBMA, basic and clinical research have deepened our understanding of the disease
      phenotype and pathophysiology. Spinal and bulbar muscular atrophy exclusively
      affects men, whereas women homozygous for the AR mutation do not fully develop
      the disease. The ligand-dependent nuclear accumulation of pathogenic AR protein
      is central to the pathogenesis, although additional steps, eg, DNA binding and
      interdomain interactions of AR, are required for toxicity. Downstream molecular
      events, eg, transcriptional dysregulation, axonal transport disruption, and
      mitochondrial dysfunction, are implicated in the neurodegeneration in SBMA.
      Pathogenic AR-induced myopathy also contributes to the degeneration of motor
      neurons. Several potential therapies, including hormonal manipulation, have
      emerged from animal studies, some of which have been tested in clinical trials.

PMID- 22158720
TI  - Acute severe animal model of anti-muscle-specific kinase myasthenia: combined
      postsynaptic and presynaptic changes.
AB  - OBJECTIVES: To determine the pathogenesis of anti-muscle-specific kinase (MuSK)
      myasthenia, a newly described severe form of myasthenia gravis associated with
      MuSK antibodies characterized by focal muscle weakness and wasting and absence of
      acetylcholine receptor antibodies, and to determine whether antibodies to MuSK, a
      crucial protein in the formation of the neuromuscular junction (NMJ) during
      development, can induce disease in the mature NMJ. Design, Setting, and
      PARTICIPANTS: Lewis rats were immunized with a single injection of a newly
      discovered splicing variant of MuSK, MuSK 60, which has been demonstrated to be
      expressed primarily in the mature NMJ. Animals were assessed clinically,
      serologically, and by repetitive stimulation of the median nerve. Muscle tissue
      was examined immunohistochemically and by electron microscopy. RESULTS: Animals
      immunized with 100 MUg of MuSK 60 developed severe progressive weakness starting
      at day 16, with 100% mortality by day 27. The weakness was associated with high
      MuSK antibody titers, weight loss, axial muscle wasting, and decrementing
      compound muscle action potentials. Light and electron microscopy demonstrated
      fragmented NMJs with varying degrees of postsynaptic muscle end plate destruction
      along with abnormal nerve terminals, lack of registration between end plates and
      nerve terminals, local axon sprouting, and extrajunctional dispersion of
      cholinesterase activity. CONCLUSIONS: These findings support the role of MuSK
      antibodies in the human disease, demonstrate the role of MuSK not only in the
      development of the NMJ but also in the maintenance of the mature synapse, and
      demonstrate involvement of this disease in both presynaptic and postsynaptic
      components of the NMJ.

PMID- 22158721
TI  - Autoimmune autonomic ganglionopathy with reversible cognitive impairment.
AB  - BACKGROUND: Autoimmune autonomic ganglionopathy (AAG) is a rare disorder of
      antibody-mediated impaired transmission across the autonomic ganglia resulting in
      severe autonomic failure. Some patients with AAG report cognitive impairment of
      unclear etiology despite treatment of autonomic symptoms. OBJECTIVE: To
      investigate the relationship between orthostatic hypotension, antibody titers,
      and cognitive impairment in patients with AAG. DESIGN: Prospective cohort.
      SETTING: Academic medical center. PARTICIPANTS: Three patients with AAG underwent
      neuropsychological testing before and after cycles of plasma exchange in both the
      seated and standing positions. MAIN OUTCOME MEASURES: Patients' responses to
      neuropsychological tests were measured by percentage change from baseline in the
      seated and standing positions before and after plasma exchange to determine the
      effects of orthostatic hypotension and antibody titers on cognition. RESULTS:
      Orthostatic hypotension and elevated antibody titer were associated independently
      with neuropsychological impairment (P < .05), particularly in domains of
      executive function, sustained attention, and working memory. Cognitive
      dysfunction improved, even in the seated normotensive position, after
      plasmapheresis and consequent reduction in antibody levels. CONCLUSION:
      Reversible cognitive impairment is independently associated with both orthostatic
      hypotension and elevated nicotinic acetylcholine receptor autoantibodies, thereby
      expanding the clinical spectrum of autonomic ganglionopathy and, in so doing,
      providing an additional treatable cause of cognitive impairment.

PMID- 22158723
TI  - An oral formulation of amphotericin B attached to functionalized carbon nanotubes
      is an effective treatment for experimental visceral leishmaniasis.
AB  - Amphotericin B (AmB), is a highly effective antileishmanial agent used as first
      line treatment in different formulations in visceral leishmaniasis endemic areas
      of Bihar, India. However, parenteral infusion, prolonged hospitalization, and
      toxicity are major hurdles. Our previous work demonstrated the efficacy and
      stability of functionalized carbon nanotubes as a delivery mechanism for AmB. In
      this study, using the hamster model, we have shown that this novel formulation of
      AmB can be administered orally, resulting in 99% inhibition of parasite growth
      following a 5-day course at 15 mg/kg body weight.

PMID- 22158724
TI  - The first observation of electroluminescence from di(2-naphthyl)disilene, an
      Si=Si double bond-containing pi-conjugated compound.
AB  - Air-stable, room-temperature emissive di(2-naphthyl)disilene, protected by the
      bulky 1,1,3,3,5,5,7,7-octaethyl-s-hydrindacen-4-yl (Eind) groups, can emit light
      in an organic light-emitting diode, thus providing the first experimental
      demonstration of electroluminescence from the heavy group 14 unsaturated
      compounds.

PMID- 22158725
TI  - Folate-responsive birth defects: of mice and women.

PMID- 22158726
TI  - Quantitative data on the magnitude of the systemic inflammatory response and its
      effect on micronutrient status based on plasma measurements.
AB  - BACKGROUND: Plasma concentrations of several trace elements and vitamins decrease
      because of the systemic inflammatory response. Thus, low values do not
      necessarily indicate deficiency. OBJECTIVE: The magnitude of this effect on
      plasma micronutrient concentrations was investigated to provide guidance on the
      interpretation of routine clinical results. DESIGN: Between 2001 and 2011, the
      results (2217 blood samples from 1303 patients) of routine micronutrient screens
      (plasma zinc, copper, selenium, and vitamins A, B-6, C, and E) and all vitamin D
      results (4327 blood samples from 3677 patients) were extracted from the
      laboratory database. C-reactive protein concentrations were measured as a marker
      of the severity of inflammation and categorized into 6 groups; for each group,
      plasma micronutrient concentrations and percentage changes were calculated.
      RESULTS: Except for copper and vitamin E, all plasma micronutrient concentrations
      decreased with increasing severities of the acute inflammatory response. For
      selenium and vitamins B-6 and C, this occurred with only slightly increased C
      reactive protein concentrations of 5 to 10 mg/L. For each micronutrient, the
      change in plasma concentrations varied markedly from patient to patient. The
      magnitude of the effect was greatest for selenium and vitamins A, B-6, C, and D,
      for which the median plasma concentrations decreased by >40%. CONCLUSIONS: The
      clinical interpretation of plasma micronutrients can be made only with knowledge
      of the degree of inflammatory response. A reliable clinical interpretation can be
      made only if the C-reactive protein is <20 mg/L (plasma zinc), <10 mg/L (plasma
      selenium and vitamins A and D), or <5 mg/L (vitamins B-6 and C).

PMID- 22158728
TI  - Increasing food acceptance in the home setting: a randomized controlled trial of
      parent-administered taste exposure with incentives.
AB  - BACKGROUND: The use of rewards to encourage children to eat healthily is
      controversial. However, researcher-led interventions have shown that incentives
      combined with taste exposure can increase both intake and liking. To date, this
      has not been tested in the home setting. OBJECTIVES: The objectives were to test
      the hypothesis that parent-administered repeated taste exposures to an initially
      disliked vegetable combined with reward will increase children's liking and
      intake and to compare the effects of tangible and social rewards. DESIGN: In this
      randomized controlled trial, families with children aged 3-4 y (n = 173) were
      randomly assigned to exposure + tangible reward (sticker), exposure + social
      reward (praise), or no-treatment control conditions after a pretest assessment in
      which a target vegetable was selected for each child. In the intervention groups,
      parents offered their children 12 daily tastes of the vegetable, giving either
      praise or a sticker for tasting. No specific advice was given to the control
      group. Assessments of intake and liking of the target vegetable were conducted by
      researchers immediately after the intervention period and 1 and 3 mo later.
      RESULTS: Children who received exposure + tangible rewards increased their intake
      (P = 0.001) and liking (P = 0.001) of their target vegetable significantly more
      than did children in the control group. Differences were maintained at the 3-mo
      follow-up (intake: P = 0.005; liking: P = 0.001). Increases in intake and liking
      in the exposure + social reward group were not significantly different from the
      control group. CONCLUSION: The findings of this home-based study support parental
      use of tangible rewards with repeated taste exposures to improve children's
      diets. This trial is registered as ISRCTN42922680.

PMID- 22158727
TI  - Effects of different sweet preloads on incretin hormone secretion, gastric
      emptying, and postprandial glycemia in healthy humans.
AB  - BACKGROUND: Macronutrient "preloads" can stimulate glucagon-like peptide 1 (GLP
      1) and glucose-dependent insulinotropic polypeptide (GIP), slow gastric emptying,
      and reduce postprandial glycemic excursions. After sweet preloads, these effects
      may be signaled by sodium-glucose cotransporter-1 (SGLT1), sweet taste receptors,
      or both. OBJECTIVE: We determined the effects of 4 sweet preloads on GIP and GLP
      1 release, gastric emptying, and postprandial glycemia. DESIGN: Ten healthy
      subjects were studied on 4 separate occasions each. A preload drink containing 40
      g glucose, 40 g tagatose/isomalt mixture (TIM), 40 g 3-O-methylglucose (3OMG; a
      nonmetabolized substrate of SGLT1), or 60 mg sucralose was consumed 15 min before
      a (13)C-octanoic acid-labeled mashed potato meal. Blood glucose, plasma total GLP
      1 and GIP, serum insulin, and gastric emptying were determined. RESULTS: Both
      glucose and 3OMG stimulated GLP-1 and GIP release in advance of the meal (each P
      < 0.05), whereas TIM and sucralose did not. The overall postprandial GLP-1
      response was greater after glucose, 3OMG, and TIM than after sucralose (P <
      0.05), albeit later after TIM than the other preloads. The blood glucose and
      insulin responses in the first 30 min after the meal were greatest after glucose
      (each P < 0.05). Gastric emptying was slower after both 3OMG and TIM than after
      sucralose (each P < 0.05). CONCLUSIONS: In healthy humans, SGLT1 substrates
      stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are
      metabolized, whereas the artificial sweetener sucralose does not. Poorly absorbed
      sweet tastants (TIM), which probably expose a greater length of gut to nutrients,
      result in delayed GLP-1 secretion but not in delayed GIP release. These
      observations have the potential to optimize the use of preloads for glycemic
      control. This trial was registered at www.actr.org.au as ACTRN12611000775910.

PMID- 22158729
TI  - Protein status elicits compensatory changes in food intake and food preferences.
AB  - BACKGROUND: Protein is an indispensable component within the human diet. It is
      unclear, however, whether behavioral strategies exist to avoid shortages.
      OBJECTIVE: The objective was to investigate the effect of a low protein status
      compared with a high protein status on food intake and food preferences. DESIGN:
      We used a randomized crossover design that consisted of a 14-d fully controlled
      dietary intervention involving 37 subjects [mean +/- SD age: 21 +/- 2 y; BMI (in
      kg/m(2)): 21.9 +/- 1.5] who consumed individualized, isoenergetic diets that were
      either low in protein [0.5 g protein . kg body weight (BW)(-1) . d(-1)] or high
      in protein (2.0 g protein . kg BW(-1) . d(-1)). The diets were followed by an ad
      libitum phase of 2.5 d, during which a large array of food items was available,
      and protein and energy intakes were measured. RESULTS: We showed that in the ad
      libitum phase protein intake was 13% higher after the low-protein diet than after
      the high-protein diet (253 +/- 70 compared with 225 +/- 63 g, P < 0.001), whereas
      total energy intake was not different. The higher intake of protein was evident
      throughout the ad libitum phase of 2.5 d. In addition, after the low-protein
      diet, food preferences for savory high-protein foods were enhanced. CONCLUSIONS:
      After a protein deficit, food intake and food preferences show adaptive changes
      that suggest that compensatory mechanisms are induced to restore adequate protein
      status. This indicates that there are human behavioral strategies present to
      avoid protein shortage and that these involve selection of savory high-protein
      foods. This trial was registered with the Dutch Trial register at
      http://www.trialregister.nl as NTR2491.

PMID- 22158730
TI  - Effects of increased dietary protein-to-carbohydrate ratios in women with
      polycystic ovary syndrome.
AB  - BACKGROUND: Some evidence has suggested that a diet with a higher ratio of
      protein to carbohydrates has metabolic advantages in the treatment of polycystic
      ovary syndrome (PCOS). OBJECTIVE: The objective of this study was to compare the
      effect of a high-protein (HP) diet to a standard-protein (SP) diet in women with
      PCOS. DESIGN: A controlled, 6-mo trial was conducted in 57 PCOS women. The women
      were assigned through rank minimization to one of the following 2 diets without
      caloric restriction: an HP diet (>40% of energy from protein and 30% of energy
      from fat) or an SP diet (<15% of energy from protein and 30% of energy from fat).
      The women received monthly dietary counseling. At baseline and 3 and 6 mo,
      anthropometric measurements were performed, and blood samples were collected.
      RESULTS: Seven women dropped out because of pregnancy, 23 women dropped out
      because of other reasons, and 27 women completed the study. The HP diet produced
      a greater weight loss (mean: 4.4 kg; 95% CI: 0.3, 8.6 kg) and body fat loss
      (mean: 4.3 kg; 95% CI: 0.9, 7.6 kg) than the SP diet after 6 mo. Waist
      circumference was reduced more by the HP diet than by the SP diet. The HP diet
      produced greater decreases in glucose than did the SP diet, which persisted after
      adjustment for weight changes. There were no differences in testosterone, sex
      hormone-binding globulin, and blood lipids between the groups after 6 mo.
      However, adjustment for weight changes led to significantly lower testosterone
      concentrations in the SP-diet group than in the HP-diet group. CONCLUSION:
      Replacement of carbohydrates with protein in ad libitum diets improves weight
      loss and improves glucose metabolism by an effect that seems to be independent of
      the weight loss and, thus, seems to offer an improved dietary treatment of PCOS
      women.

PMID- 22158732
TI  - The number of maximum matchings in a tree.
AB  - We determine upper and lower bounds for the number of maximum matchings (i.e.,
      matchings of maximum cardinality) [Formula: see text] of a tree T of given order.
      While the trees that attain the lower bound are easily characterised, the trees
      with the largest number of maximum matchings show a very subtle structure. We
      give a complete characterisation of these trees and derive that the number of
      maximum matchings in a tree of order n is at most [Formula: see text] (the
      precise constant being an algebraic number of degree 14). As a corollary, we
      improve on a recent result by Gorska and Skupien on the number of maximal
      matchings (maximal with respect to set inclusion).

PMID- 22158731
TI  - Two-year sustained weight loss and metabolic benefits with controlled-release
      phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized,
      placebo-controlled, phase 3 extension study.
AB  - BACKGROUND: Obesity is a serious chronic disease. Controlled-release
      phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification,
      has previously shown significant weight loss compared with placebo in a 56-wk
      study in overweight and obese subjects with >=2 weight-related comorbidities.
      OBJECTIVE: This study evaluated the long-term efficacy and safety of PHEN/TPM CR
      in overweight and obese subjects with cardiometabolic disease. DESIGN: This was a
      placebo-controlled, double-blind, 52-wk extension study; volunteers at selected
      sites continued with original randomly assigned treatment [placebo, 7.5 mg
      phentermine/46 mg controlled-release topiramate (7.5/46), or 15 mg phentermine/92
      mg controlled-release topiramate (15/92)] to complete a total of 108 wk. All
      subjects participated in a lifestyle-modification program. RESULTS: Of 866
      eligible subjects, 676 (78%) elected to continue in the extension. Overall, 84.0%
      of subjects completed the study, with similar completion rates between treatment
      groups. At week 108, PHEN/TPM CR was associated with significant, sustained
      weight loss (intent-to-treat with last observation carried forward; P < 0.0001
      compared with placebo); least-squares mean percentage changes from baseline in
      body weight were -1.8%, -9.3%, and -10.5% for placebo, 7.5/46, and 15/92,
      respectively. Significantly more PHEN/TPM CR-treated subjects at each dose
      achieved >=5%, >=10%, >=15%, and >=20% weight loss compared with placebo (P <
      0.001). PHEN/TPM CR improved cardiovascular and metabolic variables and decreased
      rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well
      tolerated over 108 wk, with reduced rates of adverse events occurring between
      weeks 56 and 108 compared with rates between weeks 0 and 56. CONCLUSION: PHEN/TPM
      CR in conjunction with lifestyle modification may provide a well-tolerated and
      effective option for the sustained treatment of obesity complicated by
      cardiometabolic disease. This trial was registered at clinicaltrials.gov as
      NCT00796367.

PMID- 22158735
TI  - On the flexibility of lizards' cognition: a comment on Leal & Powell (2011).

PMID- 22158736
TI  - Real estate ads in Emei music frog vocalizations: female preference for calls
      emanating from burrows.
AB  - During female mate choice, both the male's phenotype and resources (e.g. his
      nest) contribute to the chooser's fitness. Animals other than humans are not
      known to advertise resource characteristics to potential mates through vocal
      communication; although in some species of anurans and birds, females do evaluate
      male qualities through vocal communication. Here, we demonstrate that calls of
      the male Emei music frog (Babina dauchina), vocalizing from male-built nests,
      reflect nest structure information that can be recognized by females. Inside-nest
      calls consisted of notes with energy concentrated at lower frequency ranges and
      longer note durations when compared with outside-nest calls. Centre frequencies
      and note durations of the inside calls positively correlate with the area of the
      burrow entrance and the depth of the burrow, respectively. When given a choice
      between outside and inside calls played back alternately, more than 70 per cent
      of the females (33/47) chose inside calls. These results demonstrate that males
      of this species faithfully advertise whether or not they possess a nest to
      potential mates by vocal communication, which probably facilitates optimal mate
      selection by females. These results revealed a novel function of advertisement
      calls, which is consistent with the wide variation in both call complexity and
      social behaviour within amphibians.

PMID- 22158737
TI  - A cockroach that jumps.
AB  - We report on a newly discovered cockroach (Saltoblattella montistabularis) from
      South Africa, which jumps and therefore differs from all other extant cockroaches
      that have a scuttling locomotion. In its natural shrubland habitat, jumping and
      hopping accounted for 71 per cent of locomotory activity. Jumps are powered by
      rapid and synchronous extension of the hind legs that are twice the length of the
      other legs and make up 10 per cent of the body weight. In high-speed images of
      the best jumps the body was accelerated in 10 ms to a take-off velocity of 2.1 m
      s(-1) so that the cockroach experienced the equivalent of 23 times gravity while
      leaping a forward distance of 48 times its body length. Such jumps required 38 uJ
      of energy, a power output of 3.4 mW and exerted a ground reaction force through
      both hind legs of 4 mN. The large hind legs have grooved femora into which the
      tibiae engage fully in advance of a jump, and have resilin, an elastic protein,
      at the femoro-tibial joint. The extensor tibiae muscles contracted for 224 ms
      before the hind legs moved, indicating that energy must be stored and then
      released suddenly in a catapult action to propel a jump. Overall, the jumping
      mechanisms and anatomical features show remarkable convergence with those of
      grasshoppers with whom they share their habitat and which they rival in jumping
      performance.

PMID- 22158738
TI  - Prey detection in a cruising copepod.
AB  - Small cruising zooplankton depend on remote prey detection and active prey
      capture for efficient feeding. Direct, passive interception of prey is inherently
      very inefficient at low Reynolds numbers because the viscous boundary layer
      surrounding the approaching predator will push away potential prey. Yet, direct
      interception has been proposed to explain how rapidly cruising, blind copepods
      feed on non-motile phytoplankton prey. Here, we demonstrate a novel mechanism for
      prey detection in a cruising copepod, and describe how motile and non-motile prey
      are discovered by hydromechanical and tactile or, likely, chemical cues,
      respectively.

PMID- 22158739
TI  - Identification of antigen-specific antibody responses associated with upper
      genital tract pathology in mice infected with Chlamydia muridarum.
AB  - Urogenital infection with Chlamydia trachomatis in some women can lead to upper
      genital tract pathologies, such as hydrosalpinx, potentially affecting fertility.
      In the current study, 27 of 40 mice intravaginally infected with Chlamydia
      muridarum developed visible hydrosalpinges in the oviduct while the remaining 13
      did not, although all infected mice displayed similar infection time courses.
      Antisera from the 40 mice recognized 130 out of 257 C. muridarum proteins as
      antigens and 17 as immunodominant antigens. Importantly, the 27 mice with
      hydrosalpinges preferentially recognized two C. muridarum proteins (TC0582 and
      TC0912, designated pathology-associated antigens) while the 13 mice with no
      hydrosalpinx preferentially recognized 10 proteins (TC0047, TC0117, TC0190,
      TC0197, TC0257, TC0279, TC0326, TC0630, TC0689, and TC0816, designated
      nonpathology antigens). The preferential recognition was validated by absorption
      and independently confirmed in Western blots. The C. trachomatis homolog of
      TC0912 is encoded by a highly polymorphic gene that is associated with ocular
      pathogenesis. A fragment of TC0912 was found to improve the differentiation of
      hydrosalpinx from nonhydrosalpinx mice. TC0582 is a highly conserved ATP
      synthase, and it may contribute to chlamydial pathogenesis via mechanisms similar
      to those hypothesized for the highly conserved HSP60. Thus, we have identified
      chlamydial antigens and epitopes that are associated with either susceptibility
      or resistance to upper genital tract pathology, which will help us to further
      understand chlamydial pathogenesis and to develop anti-Chlamydia subunit
      vaccines.

PMID- 22158740
TI  - Mucosal immunization with an unadjuvanted vaccine that targets Streptococcus
      pneumoniae PspA to human Fcgamma receptor type I protects against pneumococcal
      infection through complement- and lactoferrin-mediated bactericidal activity.
AB  - Targeting an antigen to Fc receptors (FcR) can enhance the immune response to the
      antigen in the absence of adjuvant. Furthermore, we recently demonstrated that
      intranasal immunization with an FcgammaR-targeted antigen enhances protection
      against a category A intracellular mucosal pathogen, Francisella tularensis. To
      determine if a similar strategy could be applied to the important pathogen
      Streptococcus pneumoniae, we used an improved mucosal FcR-targeting strategy that
      specifically targets human FcgammaR type I (hFcgammaRI). A humanized single-chain
      antibody component in which the variable domain binds to hFcgammaRI [anti
      hFcgammaRI (H22)] was linked in a fusion protein with the pneumococcal surface
      protein A (PspA). PspA is known to elicit protection against pneumococcal sepsis,
      carriage, and pneumonia in mouse models when administered with adjuvants. Anti
      hFcgammaRI-PspA or recombinant PspA (rPspA) alone was used to intranasally
      immunize wild-type (WT) and hFcgammaRI transgenic (Tg) mice in the absence of
      adjuvant. The hFcgammaRI Tg mice receiving anti-hFcgammaRI-PspA exhibited
      elevated S. pneumoniae-specific IgA, IgG2c, and IgG1 antibodies in serum and
      bronchoalveolar lavage fluid. Neither immunogen was effective in protecting WT
      mice in the absence of adjuvant, but when PspA was targeted to hFcgammaRI as the
      anti-hFcgammaRI-PspA fusion, enhanced protection against lethal S. pneumoniae
      challenge was observed in the hFcgammaRI Tg mice compared to mice given
      nontargeted rPspA alone. Immune sera from the anti-hFcgammaRI-PspA-immunized Tg
      mice showed enhanced complement C3 deposition on bacterial surfaces, and
      protection was dependent upon an active complement system. Immune serum also
      showed an enhanced bactericidal activity directed against S. pneumoniae that
      appears to be lactoferrin mediated.

PMID- 22158741
TI  - In vivo-induced InvA-like autotransporters Ifp and InvC of Yersinia
      pseudotuberculosis promote interactions with intestinal epithelial cells and
      contribute to virulence.
AB  - The Yersinia pseudotuberculosis Ifp and InvC molecules are putative
      autotransporter proteins with a high homology to the invasin (InvA) protein. To
      characterize the function of these surface proteins, we expressed both factors in
      Escherichia coli K-12 and demonstrated the attachment of Ifp- and InvC-expressing
      bacteria to human-, mouse-, and pig-derived intestinal epithelial cells. Ifp also
      was found to mediate microcolony formation and internalization into polarized
      human enterocytes. The ifp and invC genes were not expressed under in vitro
      conditions but were found to be induced in the Peyer's patches of the mouse
      intestinal tract. In a murine coinfection model, the colonization of the Peyer's
      patches and the mesenteric lymph nodes of mice by the ifp-deficient strain was
      significantly reduced, and considerably fewer bacteria reached liver and spleen.
      The absence of InvC did not have a severe influence on bacterial colonization in
      the murine infection model, and it resulted in only a slightly reduced number of
      invC mutants in the Peyer's patches. The analysis of the host immune response
      demonstrated that the presence of Ifp and InvC reduced the recruitment of
      professional phagocytes, especially neutrophils, in the Peyer's patches. These
      findings support a role for the adhesins in modulating host-pathogen interactions
      that are important for immune defense.

PMID- 22158743
TI  - Phenotypic modulation of the virulent Bvg phase is not required for pathogenesis
      and transmission of Bordetella bronchiseptica in swine.
AB  - The majority of virulence gene expression in Bordetella is regulated by a two
      component sensory transduction system encoded by the bvg locus. In response to
      environmental cues, the BvgAS regulatory system controls expression of a spectrum
      of phenotypic phases, transitioning between a virulent (Bvg(+)) phase and a
      nonvirulent (Bvg(-)) phase, a process referred to as phenotypic modulation. We
      hypothesized that the ability of Bordetella bronchiseptica to undergo phenotypic
      modulation is required at one or more points during the infectious cycle in
      swine. To investigate the Bvg phase-dependent contribution to pathogenesis of B.
      bronchiseptica in swine, we constructed a series of isogenic mutants in a
      virulent B. bronchiseptica swine isolate and compared each mutant to the wild
      type isolate for its ability to colonize and cause disease. We additionally
      tested whether a BvgAS system capable of modulation is required for direct or
      indirect transmission. The Bvg(-) phase-locked mutant was never recovered from
      any respiratory tract site at any time point examined. An intermediate phase
      locked mutant (Bvg(i)) was found in numbers lower than the wild type at all
      respiratory tract sites and time points examined and caused limited to no
      disease. In contrast, colonization of the respiratory tract and disease caused by
      the Bvg(+) phase-locked mutant and the wild-type strain were indistinguishable.
      The Bvg(+) phase-locked mutant transmitted to naive pigs by both direct and
      indirect contact with efficiency equal to that of the wild-type isolate. These
      results indicate that while full activation of the BvgAS regulatory system is
      required for colonization and severe disease, it is not deleterious to direct and
      indirect transmission. Overall, our results demonstrate that the Bvg(+) phase is
      sufficient for respiratory infection and host-to-host transmission of B.
      bronchiseptica in swine.

PMID- 22158742
TI  - Identification of components of the host type IA phosphoinositide 3-kinase
      pathway that promote internalization of Listeria monocytogenes.
AB  - The bacterial pathogen Listeria monocytogenes causes food-borne illnesses
      resulting in gastroenteritis, meningitis, or abortion. Listeria promotes its
      internalization into some human cells through binding of the bacterial surface
      protein InlB to the host receptor tyrosine kinase Met. The interaction of InlB
      with the Met receptor stimulates host signaling pathways that promote cell
      surface changes driving bacterial uptake. One human signaling protein that plays
      a critical role in Listeria entry is type IA phosphoinositide 3-kinase (PI 3
      kinase). The molecular mechanism by which PI 3-kinase promotes bacterial
      internalization is not understood. Here we perform an RNA interference (RNAi)
      based screen to identify components of the type IA PI 3-kinase pathway that
      control the entry of Listeria into the human cell line HeLa. The 64 genes
      targeted encode known upstream regulators or downstream effectors of type IA PI 3
      kinase. The results of this screen indicate that at least 9 members of the PI 3
      kinase pathway play important roles in Listeria uptake. These 9 human proteins
      include a Rab5 GTPase, several regulators of Arf or Rac1 GTPases, and the
      serine/threonine kinases phosphoinositide-dependent kinase 1 (PDK1), mammalian
      target of rapamycin (mTor), and protein kinase C-zeta. These findings represent a
      key first step toward understanding the mechanism by which type IA PI 3-kinase
      controls bacterial internalization.

PMID- 22158744
TI  - Experimental cerebral malaria develops independently of caspase recruitment
      domain-containing protein 9 signaling.
AB  - The outcome of infection depends on multiple layers of immune regulation, with
      innate immunity playing a decisive role in shaping protection or pathogenic
      sequelae of acquired immunity. The contribution of pattern recognition receptors
      and adaptor molecules in immunity to malaria remains poorly understood. Here, we
      interrogate the role of the caspase recruitment domain-containing protein 9
      (CARD9) signaling pathway in the development of experimental cerebral malaria
      (ECM) using the murine Plasmodium berghei ANKA infection model. CARD9 expression
      was upregulated in the brains of infected wild-type (WT) mice, suggesting a
      potential role for this pathway in ECM pathogenesis. However, P. berghei ANKA
      infected Card9(-/-) mice succumbed to neurological signs and presented with
      disrupted blood-brain barriers similar to WT mice. Furthermore, consistent with
      the immunological features associated with ECM in WT mice, Card9(-/-) mice
      revealed (i) elevated levels of proinflammatory responses, (ii) high frequencies
      of activated T cells, and (iii) CD8(+) T cell arrest in the cerebral
      microvasculature. We conclude that ECM develops independently of the CARD9
      signaling pathway.

PMID- 22158746
TI  - Classification of GABA and benzodiazepine receptors.

PMID- 22158747
TI  - Agoraphobia, panic disorder and related conditions in the DSM-IIIR and ICD-10.

PMID- 22158745
TI  - Interleukin-1beta regulates CXCL8 release and influences disease outcome in
      response to Streptococcus pneumoniae, defining intercellular cooperation between
      pulmonary epithelial cells and macrophages.
AB  - The success of Streptococcus pneumoniae (the pneumococcus) as a pulmonary
      pathogen is related to its restriction of innate immune responses by respiratory
      epithelial cells. The mechanisms used to overcome this restriction are
      incompletely elucidated. Pulmonary chemokine expression involves complex cellular
      and molecular networks, involving the pulmonary epithelium, but the specific
      cellular interactions and the cytokines that control them are incompletely
      defined. We show that serotype 2 or 4 pneumococci induce only modest levels of
      CXCL8 expression from epithelial cell lines, even in the absence of a
      polysaccharide capsule. In contrast, coculture of A549 cells with the macrophage
      like THP-1 cell line, differentiated with vitamin D, or monocyte-derived
      macrophages enhanced CXCL8 release. Supernatants from the THP-1 cell line prime
      A549 cells to release CXCL8 at levels similar to cocultures. Interleukin-1Ra (IL
      1Ra) inhibits CXCL8 release from cocultures and reduces the activity of
      macrophage-conditioned media, but inhibition of tumor necrosis factor alpha (TNF
      alpha) had only a minimal effect on CXCL8 release. Release of IL-1beta but not
      TNF-alpha was upregulated in cocultures. IL-1 type 1 receptor knockout C57BL/6
      and BALB/c mice confirmed the importance of IL-1 signaling in CXC chemokine
      expression and neutrophil recruitment in vivo. In fulminant disease, increased IL
      1 signaling resulted in increased neutrophils in the airway and more invasive
      disease. These results demonstrate that IL-1 is an important component of the
      cellular network involving macrophages and epithelial cells, which facilitates
      CXC chemokine expression and aids neutrophil recruitment during pneumococcal
      pneumonia. They also highlight a potential clinical role for anti-IL-1 treatment
      to limit excessive neutrophilic inflammation in the lung.

PMID- 22158748
TI  - Switch from depression to mania, or from mania to depression.
AB  - By means of two retrospective record studies of 300 patients hospitalized for
      mania, and 906 patients hospitalized for depression, the rate and point of switch
      from mania to depression and from depression to mania between 1920 and 1981 were
      investigated. The switch rate is mainly explained by polarity; patients with a
      previous history of mania/ hypomania have switch rates of 21 per cent (mania to
      depression) to 29 per cent (depression to mania)-in prospective studies the rates
      are around 30 per cent. Unipolar depressive patients have a switch rate of 2.7
      4.6 per cent, which may be due to potential bipolars. The switches occur about 4
      months after onset of the episodes and about 7 weeks after hospital admission
      (medians). The lack of any significant change within this time period does not
      support the existence of a substantial drug-induced switch. The majority of
      switches seem to occur as a consequence of the spontaneous course of bipolar
      illness.

PMID- 22158749
TI  - Effects of a phosphodiesterase inhibitor (Rolipram) on the urinary excretion of 6
      sulphatoxy melatonin in man.
AB  - The urinary excretion of 6-sulphatoxymelatonin (aMT6s) from 2400 to 0600 h was
      significantly increased following the treatment of ten normal volunteers with a
      phospho diesterase inhibitor (rolipram 1 mg 8 h for 24 h). The urinary excretion
      of the metabolite from 0600 to 1200 h was significantly reduced after treatment
      with rolipram.

PMID- 22158750
TI  - The 5-HT1A agonists 8-OH-DPAT, buspirone and ipsapirone attenuate stress-induced
      anorexia in rats.
AB  - The effects of 5-HT agonists and antagonists, benzodiazepine anxiolytics and
      tricyclic antidepressants on restraint stress-induced anorexia in rats were
      examined. The selective 5-HT(1A) agonists 8-hydroxy-2-(di- n-propylamino)tetralin
      (8-OH-DPAT), buspirone and ipsapirone, when injected 2 h after the termination of
      stress, attenuated stress-induced anor exia and body weight loss. The effects of
      8-OH-DPAT on stress-induced anorexia were blocked by the 5-HT(1A) antagonist
      spiperone but not by the 5-HT(2) antagonist ketanserin. The preferential 5-HT(1B)
      agonists RU-24969 and quipazine induced anorexia in unstressed rats and tended to
      supplement the anorectic effects of stress. The benzodiazepines chlordiazepoxide
      and diazepam and the 5-HT antagonist cyproheptadine had no effect on stress
      induced anorexia, when given (like the 5-HT(1A) agonists) 2 h after the stress.
      Similarly, daily injection for 2 weeks of the tricyclic antidepressants
      desipramine and sertraline had no beneficial effect. The data suggest that 8-OH
      DPAT, buspirone and ipsapirone attenuate stress-induced anorexia in rodents by a
      hyperphagic action on 5-HT(1A) receptors.

PMID- 22158751
TI  - Paroxetine and the electroencephalogram.
AB  - Electroencephalograms, recorded before and after 4 weeks' treatment with parox
      etine or placebo, were assessed blind to patient, treatment and treatment
      interval. No signifi cant differences were found between the paroxetine and the
      placebo groups. There were no signs of drowsiness or epileptiform activity in the
      recordings of patients receiving either drug or placebo. The results are
      discussed in relation to those of pharmacological studies in animals, psychomotor
      testing and electroencephalographic studies in humans.

PMID- 22158752
TI  - Kindling and withdrawal changes at the benzodiazepine receptor.
AB  - Drugs acting at benzodiazepine receptors can have two types of pharmacological
      profile: benzodiazepine agonists are anxiolytic, anticonvulsant and sedative,
      whilst benzo diazepine inverse agonists cause anxiety and convulsions. In 1982 we
      showed that a benzo diazepine antagonist, Ro 15-1788, prevented the effects of
      both types of compound at doses without intrinsic activity in the tests used. We
      put forward the hypothesis that the benzo diazepine receptor complex could
      undergo two possible conformational changes, resulting in increases
      (benzodiazepine agonists) or decreases (benzodiazepine inverse agonists) in the
      effects of the inhibitory transmitter gamma-aminobutyric acid (GABA). This
      concept has been widely accepted. We have now studied the effects of inverse
      agonists after chronic treatment with inverse agonists themselves and with
      benzodiazepine agonists, in order to see if tolerance develops (as seen with the
      agonists) or whether an opposite change occurs.

PMID- 22158753
TI  - Effects of dopamine antagonists on fluid intake and salt preference in male and
      female rats.
AB  - The effects of three dopamine antagonists (pimozide, clozapine, sulpiride) on
      fluid consumption by water-deprived rats trained to choose between a saline
      solution and water in a 15 min drinking test were examined. Rats of each sex were
      allocated to three groups and given access to 0.125% NaCl, 0.6% NaCl, and 1.7%
      NaCl, respectively, as the alternative to water. Dose-dependent reductions in
      fluid consumption were produced by pimozide (0.1- 3.0 mg kg(-1)) and clozapine
      (0.3-10.0 mg kg(-1)), but not by sulpiride (1.0-30 mg kg(-1)). There were
      instances of a hyperdipsic effect of sulpiride. The dopamine antagonists produced
      significant changes in saline preference, but in no case was a decrease in
      preference detected. Instead, there was evidence for induction of preference, or
      enhancement of preference, in both sexes. So far as determinants of preference
      for the salt are concerned, it appears that in the rat, dopamine may have a
      predominantly inhibitory action.

PMID- 22158754
TI  - Symposium abstracts.

PMID- 22158755
TI  - Editorial.

PMID- 22158757
TI  - Connexins and atrial fibrillation: filling in the gaps.

PMID- 22158756
TI  - Connexin gene transfer preserves conduction velocity and prevents atrial
      fibrillation.
AB  - BACKGROUND: Several lines of evidence have suggested that maintenance of atrial
      fibrillation (AF) depends on reentrant mechanisms. Maintenance of reentry
      necessitates a sufficiently short refractory period and/or delayed conduction,
      and AF has been associated with both alterations. Fibrosis, cellular dysfunction,
      and gap junction protein alterations occur in AF and cause conduction delay. We
      performed this study to test the hypothesis that gap junction protein
      overexpression would improve conduction and prevent AF. METHODS AND RESULTS:
      Thirty Yorkshire swine were randomized into 2 groups (sinus rhythm and AF), and
      each group into 3 subgroups: sham-operated control, gene therapy with adenovirus
      expressing connexin (Cx) 40, and gene therapy with adenovirus expressing Cx43
      (n=5 per subgroup). All animals had epicardial gene painting; the AF group had
      burst atrial pacing. All animals underwent terminal study 7 days after gene
      transfer. Sinus rhythm animals had strong transgene expression but no atrial
      conduction changes. In AF animals, controls had reduced and lateralized Cx43
      expression, and Cx43 gene transfer restored expression and cellular location to
      sinus rhythm control levels. In the AF group, both Cx40 and Cx43 gene transfer
      improved conduction and reduced AF relative to controls. CONCLUSIONS: Connexin
      gene therapy preserved atrial conduction and prevented AF.

PMID- 22158758
TI  - Colorimetric logic gates based on aptamer-crosslinked hydrogels.
AB  - We have developed a novel molecular logic gate system based on the incorporation
      of aptamer-crosslinked hydrogels. Modified gold nanoparticles are used as the
      output signal, which is visible to the naked eye. This system is designed for AND
      and OR operations using two chemicals as stimulus inputs.

PMID- 22158759
TI  - A single ancient origin for prototypical serine/arginine-rich splicing factors.
AB  - Eukaryotic precursor mRNA splicing is a process involving a very complex RNA
      protein edifice. Serine/arginine-rich (SR) proteins play essential roles in
      precursor mRNA constitutive and alternative splicing and have been suggested to
      be crucial in plant-specific forms of developmental regulation and environmental
      adaptation. Despite their functional importance, little is known about their
      origin and evolutionary history. SR splicing factors have a modular organization
      featuring at least one RNA recognition motif (RRM) domain and a carboxyl-terminal
      region enriched in serine/arginine dipeptides. To investigate the evolution of SR
      proteins, we infer phylogenies for more than 12,000 RRM domains representing more
      than 200 broadly sampled organisms. Our analyses reveal that the RRM domain is
      not restricted to eukaryotes and that all prototypical SR proteins share a single
      ancient origin, including the plant-specific SR45 protein. Based on these
      findings, we propose a scenario for their diversification into four natural
      families, each corresponding to a main SR architecture, and a dozen subfamilies,
      of which we profile both sequence conservation and composition. Finally, using
      operational criteria for computational discovery and classification, we catalog
      SR proteins in 20 model organisms, with a focus on green algae and land plants.
      Altogether, our study confirms the homogeneity and antiquity of SR splicing
      factors while establishing robust phylogenetic relationships between animal and
      plant proteins, which should enable functional analyses of lesser characterized
      SR family members, especially in green plants.

PMID- 22158760
TI  - A deletion in NRT2.1 attenuates Pseudomonas syringae-induced hormonal
      perturbation, resulting in primed plant defenses.
AB  - For an efficient defense response against pathogens, plants must coordinate rapid
      genetic reprogramming to produce an incompatible interaction. Nitrate
      Trasnporter2 (NRT2) gene family members are sentinels of nitrate availability. In
      this study, we present an additional role for NRT2.1 linked to plant resistance
      against pathogens. This gene antagonizes the priming of plant defenses against
      the bacterial pathogen Pseudomonas syringae pv tomato DC3000 (Pst). The nrt2
      mutant (which is deficient in two genes, NRT2.1 and NRT2.2) displays reduced
      susceptibility to this bacterium. We demonstrate that modifying environmental
      conditions that stimulate the derepression of the NRT2.1 gene influences
      resistance to Pst independently of the total level of endogenous nitrogen.
      Additionally, hormonal homeostasis seemed to be affected in nrt2, which displays
      priming of salicylic acid signaling and concomitant irregular functioning of the
      jasmonic acid and abscisic acid pathways upon infection. Effector-triggered
      susceptibility and hormonal perturbation by the bacterium seem to be altered in
      nrt2, probably due to reduced sensitivity to the bacterial phytotoxin coronatine.
      The main genetic and metabolic targets of coronatine in Arabidopsis (Arabidopsis
      thaliana) remain largely unstimulated in nrt2 mutants. In addition, a P. syringae
      strain defective in coronatine synthesis showed the same virulence toward nrt2 as
      the coronatine-producing strain. Taken together, the reduced susceptibility of
      nrt2 mutants seems to be a combination of priming of salicylic acid-dependent
      defenses and reduced sensitivity to the bacterial effector coronatine. These
      results suggest additional functions for NRT2.1 that may influence plant disease
      resistance by down-regulating biotic stress defense mechanisms and favoring
      abiotic stress responses.

PMID- 22158761
TI  - Visualizing the genetic landscape of Arabidopsis seed performance.
AB  - Perfect timing of germination is required to encounter optimal conditions for
      plant survival and is the result of a complex interaction between molecular
      processes, seed characteristics, and environmental cues. To detangle these
      processes, we made use of natural genetic variation present in an Arabidopsis
      (Arabidopsis thaliana) Bayreuth * Shahdara recombinant inbred line population.
      For a detailed analysis of the germination response, we characterized rate,
      uniformity, and maximum germination and discuss the added value of such precise
      measurements. The effects of after-ripening, stratification, and controlled
      deterioration as well as the effects of salt, mannitol, heat, cold, and abscisic
      acid (ABA) with and without cold stratification were analyzed for these
      germination characteristics. Seed morphology (size and length) of both dry and
      imbibed seeds was quantified by using image analysis. For the overwhelming amount
      of data produced in this study, we developed new approaches to perform and
      visualize high-throughput quantitative trait locus (QTL) analysis. We show
      correlation of trait data, (shared) QTL positions, and epistatic interactions.
      The detection of similar loci for different stresses indicates that, often, the
      molecular processes regulating environmental responses converge into similar
      pathways. Seven major QTL hotspots were confirmed using a heterogeneous inbred
      family approach. QTLs colocating with previously reported QTLs and well
      characterized mutants are discussed. A new connection between dormancy, ABA, and
      a cripple mucilage formation due to a naturally occurring mutation in the
      MUCILAGE-MODIFIED2 gene is proposed, and this is an interesting lead for further
      research on the regulatory role of ABA in mucilage production and its multiple
      effects on germination parameters.

PMID- 22158763
TI  - Animal welfare: measures to support battery cage ban.

PMID- 22158762
TI  - Pet travel: tapeworm controls to remain for travelling pets.

PMID- 22158769
TI  - BCVA: changes ahead as budget for surveillance is squeezed.

PMID- 22158774
TI  - Getting to grips with hock lesions in cattle.

PMID- 22158775
TI  - Sheep health and welfare: contagious ovine digital dermatitis.

PMID- 22158776
TI  - Non-healing hoof lesions in dairy cows.

PMID- 22158777
TI  - Albumin levels predict survival in patients with heart failure and preserved
      ejection fraction.
AB  - AIMS: Low serum albumin is common in patients with systolic heart failure and is
      associated with increased mortality. However, the relationship between albumin
      and outcome in patients with heart failure and preserved ejection fraction
      (HFPEF) is not known. The aim of this study was to investigate the effect of
      serum albumin level on survival in patients with HFPEF. METHODS AND RESULTS: We
      studied 576 consecutive HFPEF patients (left ventricular ejection fraction >=50%)
      admitted to our hospital from 2006 to 2009. Standard demographics, transthoracic
      echocardiography, and routine blood testing including albumin levels were
      obtained shortly after admission. Outcome was assessed at 1 year after admission.
      Hypoalbuminaemia (<=34 g/L) was detected in 160 (28%) at admission; and all
      patients were then divided into hypoalbuminaemia and non-hypoalbuminaemia groups.
      In the hypoalbuminaemia group, the prevalence of chronic renal failure history,
      serum creatinine, and urea nitrogen levels were higher when compared with those
      without hypoalbuminaemia (all P < 0.05). Kaplan-Meier analysis showed that
      patients with hypoalbuminaemia had a significantly lower survival rate (53% vs.
      84%, log-rank chi(2) = 53.3, P < 0.001) and a higher rate of cardiovascular death
      (21.8% vs. 8.9%, log-rank chi(2) = 19.7, P < 0.001) when compared with those
      without hypoalbuminaemia. Cox regression further revealed that hypoalbuminaemia,
      a history of cerebrovascular disease, and older age were the most powerful
      independent predictors of all-cause mortality in HFPEF patients at 1 year.
      CONCLUSIONS: Hypoalbuminaemia is common in HFPEF patients and is associated with
      increased risk of death. Renal dysfunction may be the main pathophysiological
      mechanism underlying hypoalbuminaemia in HFPEF patients.

PMID- 22158778
TI  - The COACH risk engine: a multistate model for predicting survival and
      hospitalization in patients with heart failure.
AB  - AIMS: Several models for predicting the prognosis of heart failure (HF) patients
      have been developed, but all of them focus on a single outcome variable, such as
      all-cause mortality. The purpose of this study was to develop a multistate model
      for simultaneously predicting survival and HF-related hospitalization in patients
      discharged alive from hospital after recovery from acute HF. METHODS AND RESULTS:
      The model was derived in the COACH (Coordinating Study Evaluating Outcomes of
      Advising and Counseling in Heart Failure) cohort, a multicentre, randomized
      controlled trial in which 1023 patients were enrolled after hospitalization
      because of HF. External validation was attained with the FINN-AKVA (Finish Acute
      Heart Failure Study) cohort, a prospective, multicentre study with 620 patients
      hospitalized due to acute HF. The observed vs. predicted 18-month survival was
      72.1% vs. 72.3% in the derivation cohort and 71.4% vs. 71.2% in the validation
      cohort. The corresponding values of the c statistic were 0.733 [95% confidence
      interval (CI) 0.705-0.761] and 0.702 (95% CI 0.663-0.744), respectively. The
      model's accuracy in predicting HF hospitalization was excellent, with predicted
      values that closely resembled the values observed in the derivation cohort.
      CONCLUSION: The COACH risk engine accurately predicted survival and various
      measures of recurrent hospitalization in (acute) HF patients. It may therefore
      become a valuable tool in improving and personalizing patient care and optimizing
      the use of scarce healthcare resources.

PMID- 22158780
TI  - A triple helical structure supported solely by C-H...O hydrogen bonding.
AB  - A novel triple helical structure that is self-assembled by cationic molecules, 1
      acetamido-3-(2-pyrazinyl)-imidazolium, is reported. The computational analysis
      underpins that the formation of the triple helix is driven by C-H...O hydrogen
      bonding.

PMID- 22158782
TI  - Spin-orbit effects on a gold-based superatom: a relativistic Jellium model.
AB  - The inclusion of relativistic effects always brings to the scientific community
      great and stimulating surprises. To consider the spin-orbit term, which accounts
      for the interaction between the spatial and spin coordinates, requires the use of
      double point groups of symmetry in order to solve the Dirac equation or the two
      component approximation to it, leading to total angular momenta (j) functions,
      atomic or molecular spinors, instead of pure orbital angular momenta (l), atomic
      or molecular orbitals. Large and small components, derived from the Dirac
      treatment, depict wavefunctions corresponding to fermions, electrons, which are
      described for the first time for a superatom case. In addition, their behavior is
      revisited in order to clarify the effects of the inclusion of the spin-orbit
      coupling into the electronic structure calculations, which can be extended to
      other superatoms, clusters, molecules and atoms.

PMID- 22158781
TI  - Rv2468c, a novel Mycobacterium tuberculosis protein that costimulates human CD4+
      T cells through VLA-5.
AB  - Mtb regulates many aspects of the host immune response, including CD4+ T
      lymphocyte responses that are essential for protective immunity to Mtb, and Mtb
      effects on the immune system are paradoxical, having the capacity to inhibit
      (immune evasion) and to activate (adjuvant effect) immune cells. Mtb regulates
      CD4+ T cells indirectly (e.g., by manipulation of APC function) and directly, via
      integrins and TLRs expressed on T cells. We now report that previously
      uncharacterized Mtb protein Rv2468c/MT2543 can directly regulate human CD4+ T
      cell activation by delivering costimulatory signals. When combined with TCR
      stimulation (e.g., anti-CD3), Rv2468c functioned as a direct costimulator for
      CD4+ T cells, inducing IFN-gamma secretion and T cell proliferation. Studies with
      blocking antibodies and soluble RGD motifs demonstrated that Rv2468c engaged
      integrin VLA-5 (alpha5beta1) on CD4+ T cells through its FN-like RGD motif.
      Costimulation by Rv2468c induced phosphorylation of FAKs and Pyk2. These results
      reveal that by expressing molecules that mimic host protein motifs, Mtb can
      directly engage receptors on CD4+ T cells and regulate their function. Rv2468c
      induced costimulation of CD4+ T cells could have implications for TB immune
      pathogenesis and Mtb adjuvant effect.

PMID- 22158784
TI  - Science meets farming in Africa.

PMID- 22158789
TI  - Scientific funding. Is ?80 billion on the horizon for European research?

PMID- 22158783
TI  - An unsuspected property of natriuretic peptides: promotion of calcium-dependent
      catecholamine release via protein kinase G-mediated phosphodiesterase type 3
      inhibition.
AB  - BACKGROUND: Although natriuretic peptides are considered cardioprotective,
      clinical heart failure trials with recombinant brain natriuretic peptide
      (nesiritide) failed to prove it. Unsuspected proadrenergic effects might oppose
      the anticipated benefits of natriuretic peptides. METHODS AND RESULTS: We
      investigated whether natriuretic peptides induce catecholamine release in
      isolated hearts, sympathetic nerve endings (cardiac synaptosomes), and PC12 cells
      bearing a sympathetic neuron phenotype. Perfusion of isolated guinea pig hearts
      with brain natriuretic peptide elicited a 3-fold increase in norepinephrine
      release, which doubled in ischemia/reperfusion conditions. Brain natriuretic
      peptide and atrial natriuretic peptide also released norepinephrine from cardiac
      synaptosomes and dopamine from nerve growth factor-differentiated PC12 cells in a
      concentration-dependent manner. These catecholamine-releasing effects were
      associated with an increase in intracellular calcium and abolished by blockade of
      calcium channels and calcium transients, demonstrating a calcium-dependent
      exocytotic process. Activation of the guanylyl cyclase-cyclic GMP-protein-kinase
      G system with nitroprusside or membrane-permeant cyclic GMP analogs mimicked the
      proexocytotic effect of natriuretic peptides, an action associated with an
      increase in intracellular cyclic AMP (cAMP) and protein-kinase-A activity. Cyclic
      AMP enhancement resulted from an inhibition of phosphodiesterase type 3-induced
      cAMP hydrolysis. Collectively, these findings indicate that, by inhibiting
      phosphodiesterase type 3, natriuretic peptides sequentially enhance intracellular
      cAMP levels, protein kinase A activity, intracellular calcium, and catecholamine
      exocytosis. CONCLUSIONS: Our results show that natriuretic peptides, at
      concentrations likely to be reached at cardiac sympathetic nerve endings in
      advanced congestive heart failure, promote norepinephrine release via a protein
      kinase G-induced inhibition of phosphodiesterase type 3-mediated cAMP hydrolysis.
      We propose that this proadrenergic action may counteract the beneficial cardiac
      and hemodynamic effects of natriuretic peptides and thus explain the
      ineffectiveness of nesiritide as a cardiac failure medication.

PMID- 22158791
TI  - Undergraduate science. Weed-out courses hamper diversity.

PMID- 22158790
TI  - Scientific funding. Robert-Jan Smits: on tearing down silos, Horizon 2020's
      chances, and solving his 'headache'. Interview by Daniel Clery.

PMID- 22158792
TI  - Particle physics. First solid signs of the Higgs boson could be announced next
      week.

PMID- 22158794
TI  - Technology. Critics question China's indigenous innovation effort.

PMID- 22158793
TI  - Human evolutionary genetics. Genes confirm Europeans' blow to Native Americans.

PMID- 22158795
TI  - Earth observations. Congress asks NOAA to consider charging for data.

PMID- 22158797
TI  - Tsunami research. Tohoku inundation spurs hunt for ancient tsunamis.

PMID- 22158796
TI  - HIV prevention. Halting HIV/AIDS epidemics.

PMID- 22158798
TI  - Tsunami research. Did tsunamis influence Polynesian history?

PMID- 22158799
TI  - Citation impact. Saudi universities offer cash in exchange for academic prestige.

PMID- 22158800
TI  - Rethinking clinical trials: phase 1 studies insufficient.

PMID- 22158801
TI  - Rethinking clinical trials: change is coming.

PMID- 22158802
TI  - Rethinking clinical trials: biology's mysteries.

PMID- 22158803
TI  - Primitive ladder-of-life thinking has evolved.

PMID- 22158806
TI  - Environmental economics. Entertainment value: should the media pay for nature
      conservation?

PMID- 22158807
TI  - Ecology. The cost of fear.

PMID- 22158808
TI  - Plant science. Beleaguered immunity.

PMID- 22158809
TI  - Chemistry. Optimizing perovskites for the water-splitting reaction.

PMID- 22158810
TI  - Economics. Can integration tame conflicts?

PMID- 22158811
TI  - Behavior. Empathy and the laws of affect.

PMID- 22158812
TI  - Materials science. Complex colloidal assembly.

PMID- 22158813
TI  - Carving at the nanoscale: sequential galvanic exchange and Kirkendall growth at
      room temperature.
AB  - Shape control of inorganic nanocrystals is important for understanding basic size
      and shape-dependent scaling laws and is useful in a wide range of applications.
      With minor modifications in the chemical environment, it is possible to control
      the reaction and diffusion processes at room temperature, opening up a synthetic
      route for the production of polymetallic hollow nanoparticles with very different
      morphology and composition, obtained by the simultaneous or sequential action of
      galvanic replacement and the Kirkendall effect.

PMID- 22158814
TI  - Middle Stone Age bedding construction and settlement patterns at Sibudu, South
      Africa.
AB  - The Middle Stone Age (MSA) is associated with early behavioral innovations,
      expansions of modern humans within and out of Africa, and occasional population
      bottlenecks. Several innovations in the MSA are seen in an archaeological
      sequence in the rock shelter Sibudu (South Africa). At ~77,000 years ago, people
      constructed plant bedding from sedges and other monocotyledons topped with
      aromatic leaves containing insecticidal and larvicidal chemicals. Beginning at
      ~73,000 years ago, bedding was burned, presumably for site maintenance. By
      ~58,000 years ago, bedding construction, burning, and other forms of site use and
      maintenance intensified, suggesting that settlement strategies changed.
      Behavioral differences between ~77,000 and 58,000 years ago may coincide with
      population fluctuations in Africa.

PMID- 22158815
TI  - Context modularity of human altruism.
AB  - Whereas altruism drives the evolution of human cooperation, ethno-religious
      diversity has been considered to obstruct it, leading to poverty, corruption, and
      war. We argue that current research has failed to properly account for the
      institutional environment and how it affects the role diversity plays. The
      emergence of thriving, diverse communities throughout human history suggests that
      diversity does not always lead to cooperation breakdown. We conducted experiments
      in Mostar, Bosnia-Herzegovina with Catholic Croats and Muslim Bosniaks at a
      critical historic moment in the city's postwar history. Using a public goods
      game, we found that the ability to sanction is key to achieving cooperation in
      ethno-religiously diverse groups, but that sanctions succeed only in integrated
      institutional environments and fail in segregated ones. Hence, we show
      experimentally for the first time in a real-life setting that institutions of
      integration can unleash human altruism and restore cooperation in the presence of
      diversity.

PMID- 22158816
TI  - Capacity building helps pastoral women transform impoverished communities in
      Ethiopia.
AB  - Poverty, drought, and hunger devastate people on Africa's rangelands. We used an
      action-oriented approach from 2000 to 2004 to build capacity among thousands of
      pastoralists to diversify livelihoods, improve living standards, and enhance
      livestock marketing. The process included collective action, microfinance, and
      participatory education. Poor women previously burdened by domestic chores became
      leaders and rapidly changed their communities. Drought occurred from 2005 to
      2008. We assessed intervention effects on household drought resilience with a
      quasiexperimental format that incorporated survey-based comparisons of treatment
      groups with ex post controls. Interventions led to major improvements in trends
      for quality of life, wealth accumulation, hunger reduction, and risk management.
      Human capacity building can be a driver for change, generating hope and
      aspirations that set the stage for the use of new information and technology.

PMID- 22158817
TI  - Perceived predation risk reduces the number of offspring songbirds produce per
      year.
AB  - Predator effects on prey demography have traditionally been ascribed solely to
      direct killing in studies of population ecology and wildlife management.
      Predators also affect the prey's perception of predation risk, but this has not
      been thought to meaningfully affect prey demography. We isolated the effects of
      perceived predation risk in a free-living population of song sparrows by actively
      eliminating direct predation and used playbacks of predator calls and sounds to
      manipulate perceived risk. We found that the perception of predation risk alone
      reduced the number of offspring produced per year by 40%. Our results suggest
      that the perception of predation risk is itself powerful enough to affect
      wildlife population dynamics, and should thus be given greater consideration in
      vertebrate conservation and management.

PMID- 22158818
TI  - Arabidopsis EDS1 connects pathogen effector recognition to cell compartment
      specific immune responses.
AB  - Pathogen effectors are intercepted by plant intracellular nucleotide binding
      leucine-rich repeat (NB-LRR) receptors. However, processes linking receptor
      activation to downstream defenses remain obscure. Nucleo-cytoplasmic basal
      resistance regulator EDS1 (ENHANCED DISEASE SUSCEPTIBILITY1) is indispensible for
      immunity mediated by TIR (Toll-interleukin-1 receptor)-NB-LRR receptors. We show
      that Arabidopsis EDS1 molecularly connects TIR-NB-LRR disease resistance protein
      RPS4 recognition of bacterial effector AvrRps4 to defense pathways. RPS4-EDS1 and
      AvrRps4-EDS1 complexes are detected inside nuclei of living tobacco cells after
      transient coexpression and in Arabidopsis soluble leaf extracts after resistance
      activation. Forced AvrRps4 localization to the host cytoplasm or nucleus reveals
      cell compartment-specific RPS4-EDS1 defense branches. Although nuclear processes
      restrict bacterial growth, programmed cell death and transcriptional resistance
      reinforcement require nucleo-cytoplasmic coordination. Thus, EDS1 behaves as an
      effector target and activated TIR-NB-LRR signal transducer for defenses across
      cell compartments.

PMID- 22158819
TI  - Pathogen effectors target Arabidopsis EDS1 and alter its interactions with immune
      regulators.
AB  - Plant resistance proteins detect the presence of specific pathogen effectors and
      initiate effector-triggered immunity. Few immune regulators downstream of
      resistance proteins have been identified, none of which are known virulence
      targets of effectors. We show that Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1
      (EDS1), a positive regulator of basal resistance and of effector-triggered
      immunity specifically mediated by Toll-interleukin-1 receptor-nucleotide binding
      leucine-rich repeat (TIR-NB-LRR) resistance proteins, forms protein complexes
      with the TIR-NB-LRR disease resistance proteins RPS4 and RPS6 and with the
      negative immune regulator SRFR1 at a cytoplasmic membrane. Further, the cognate
      bacterial effectors AvrRps4 and HopA1 disrupt these EDS1 complexes. Tight
      association of EDS1 with TIR-NB-LRR-mediated immunity may therefore derive mainly
      from being guarded by TIR-NB-LRR proteins, and activation of this branch of
      effector-triggered immunity may directly connect to the basal resistance
      signaling pathway via EDS1.

PMID- 22158820
TI  - The competitive advantage of a dual-transporter system.
AB  - Cells use transporters of different affinities to regulate nutrient influx. When
      nutrients are depleted, low-affinity transporters are replaced by high-affinity
      ones. High-affinity transporters are helpful when concentrations of nutrients are
      low, but the advantage of reducing their abundance when nutrients are abundant is
      less clear. When we eliminated such reduced production of the Saccharomyces
      cerevisiae high-affinity transporters for phosphate and zinc, the elapsed time
      from the initiation of the starvation program until the lack of nutrients limited
      growth was shortened, and recovery from starvation was delayed. The latter
      phenotype was rescued by constitutive activation of the starvation program. Dual
      transporter systems appear to prolong preparation for starvation and to
      facilitate subsequent recovery, which may optimize sensing of nutrient depletion
      by integrating internal and external information about nutrient availability.

PMID- 22158821
TI  - Perceptual learning incepted by decoded fMRI neurofeedback without stimulus
      presentation.
AB  - It is controversial whether the adult primate early visual cortex is sufficiently
      plastic to cause visual perceptual learning (VPL). The controversy occurs
      partially because most VPL studies have examined correlations between behavioral
      and neural activity changes rather than cause-and-effect relationships. With an
      online-feedback method that uses decoded functional magnetic resonance imaging
      (fMRI) signals, we induced activity patterns only in early visual cortex
      corresponding to an orientation without stimulus presentation or participants'
      awareness of what was to be learned. The induced activation caused VPL specific
      to the orientation. These results suggest that early visual areas are so plastic
      that mere inductions of activity patterns are sufficient to cause VPL. This
      technique can induce plasticity in a highly selective manner, potentially leading
      to powerful training and rehabilitative protocols.

PMID- 22158822
TI  - Explaining seasonal fluctuations of measles in Niger using nighttime lights
      imagery.
AB  - Measles epidemics in West Africa cause a significant proportion of vaccine
      preventable childhood mortality. Epidemics are strongly seasonal, but the drivers
      of these fluctuations are poorly understood, which limits the predictability of
      outbreaks and the dynamic response to immunization. We show that measles
      seasonality can be explained by spatiotemporal changes in population density,
      which we measure by quantifying anthropogenic light from satellite imagery. We
      find that measles transmission and population density are highly correlated for
      three cities in Niger. With dynamic epidemic models, we demonstrate that measures
      of population density are essential for predicting epidemic progression at the
      city level and improving intervention strategies. In addition to epidemiological
      applications, the ability to measure fine-scale changes in population density has
      implications for public health, crisis management, and economic development.

PMID- 22158823
TI  - Empathy and pro-social behavior in rats.
AB  - Whereas human pro-social behavior is often driven by empathic concern for
      another, it is unclear whether nonprimate mammals experience a similar
      motivational state. To test for empathically motivated pro-social behavior in
      rodents, we placed a free rat in an arena with a cagemate trapped in a
      restrainer. After several sessions, the free rat learned to intentionally and
      quickly open the restrainer and free the cagemate. Rats did not open empty or
      object-containing restrainers. They freed cagemates even when social contact was
      prevented. When liberating a cagemate was pitted against chocolate contained
      within a second restrainer, rats opened both restrainers and typically shared the
      chocolate. Thus, rats behave pro-socially in response to a conspecific's
      distress, providing strong evidence for biological roots of empathically
      motivated helping behavior.

PMID- 22158824
TI  - A pseudo-differential calculus on non-standard symplectic space; Spectral and
      regularity results in modulation spaces.
AB  - The usual Weyl calculus is intimately associated with the choice of the standard
      symplectic structure on [Formula: see text]. In this paper we will show that the
      replacement of this structure by an arbitrary symplectic structure leads to a
      pseudo-differential calculus of operators acting on functions or distributions
      defined, not on [Formula: see text] but rather on [Formula: see text]. These
      operators are intertwined with the standard Weyl pseudo-differential operators
      using an infinite family of partial isometries of [Formula: see text] indexed by
      [Formula: see text]. This allows us to obtain spectral and regularity results for
      our operators using Shubin's symbol classes and Feichtinger's modulation spaces.

PMID- 22158825
TI  - Alteration of enzyme activity and enantioselectivity by biomimetic encapsulation
      in silica particles.
AB  - Direct encapsulation of esterase or lipase fused with the silica-precipitating R5
      peptide from Cylindrotheca fusiformis in silica particles afforded high yields of
      active entrapped protein. The hydrolytic activity of both enzymes against p
      nitrophenyl butyrate was similarly affected by encapsulation and the
      enantioselectivity of the esterase was both improved and inverted.

PMID- 22158826
TI  - IMAGE RECONSTRUCTION OF MULTIPHOTON MICROSCOPY DATA.
AB  - The techniques introduced in this paper allow for accurate multi-scale image
      reconstruction of multi-photon microscopy data. Multi-photon microscopy (MPM) is
      a tool for the non-invasive imaging of living organisms and tissue. The data
      acquired using this technique can contain information about the position, excited
      state lifetime, and spectra of the observed photons. The small number of photons
      collected, however, limits the quality of the reconstruction. The multiscale
      framework in this paper results in an accurate representation of both the
      intensity and excited state lifetime information. Using a multiscale
      reconstruction approach based on a penalized likelihood function, the underlying
      image is more accurately represented as compared to a naive aggregate binning
      approach.

PMID- 22158828
TI  - 'False-positive' intrathoracic impedance monitor alarm caused by amiodarone
      induced hypothyroidism in a patient with cardiac resynchronization therapy
      defibrillator.

PMID- 22158829
TI  - A single-nucleotide polymorphism in the fetal catechol-O-methyltransferase gene
      is associated with spontaneous preterm birth in African Americans.
AB  - Catechol-O-methyltransferase (COMT) activity has been reported to be higher in
      African Americans (AA) than Caucasians (Cau). COMT converts 2- and 4-hydroxy (OH)
      estrogens to 2- and 4-methoxyestrogens, respectively, and can increase estrogenic
      milieu locally in tissues. To assess whether the increased incidence of preterm
      birth (PTB) among AA women is associated with single-nucleotide polymorphism
      (SNP) in the COMT gene, we examined variations in maternal and fetal COMT genes
      and their association with pregnancy outcomes (term vs preterm pregnancies) using
      4 functional SNPs: rs4633, rs4680, rs4818, and rs6269 in both AA and Cau. We
      analyzed samples from 267 AA women (191 term and 76 preterm pregnancies) and 339
      Cau (194 term and 145 preterm pregnancies) in this study. The results showed a
      significant difference (P < .05) in allele and genotype frequencies between term
      and preterm AA and Cau women in 3 SNPs in both maternal and fetal DNA. The
      analysis revealed that in AA fetal COMT genes, SNP rs4818 is associated with PTB
      at the allele (C; P < .001), genotype (C/C; P < .01), and 2- (P < .03) and 3 (P <
      .04)-window haplotype levels. Multidimensionality reduction analysis also showed
      a significant (P < .01) association between rs4818 and PTB. In conclusion, our
      study demonstrated that a synonymous polymorphism, rs4818 in the fetal COMT gene,
      is associated with PTB in AA.

PMID- 22158830
TI  - Effect of feedstock solvent on the stability of Cu/SiO2 catalyst for vapor-phase
      hydrogenation of dimethyl oxalate to ethylene glycol.
AB  - The lifetime (200 h) of a Cu/SiO(2) catalyst under DMO-ethanol feedstock is 20
      times longer than that (10 h) of the catalyst under DMO-methanol feedstock
      without any modification of the catalyst. The stabilization effect of ethanol on
      the active centers can effectively slow down the agglomeration of copper
      particles during the hydrogenation process.

PMID- 22158827
TI  - Diabetes-induced myelin abnormalities are associated with an altered lipid
      pattern: protective effects of LXR activation.
AB  - Diabetic peripheral neuropathy (DPN) is characterized by myelin abnormalities;
      however, the molecular mechanisms underlying such deficits remain obscure. To
      uncover the effects of diabetes on myelin alterations, we have analyzed myelin
      composition. In a streptozotocin-treated rat model of diabetic neuropathy,
      analysis of sciatic nerve myelin lipids revealed that diabetes alters myelin's
      phospholipid, FA, and cholesterol content in a pattern that can modify membrane
      fluidity. Reduced expression of relevant genes in the FA biosynthetic pathway and
      decreased levels of the transcriptionally active form of the lipogenic factor
      sterol-regulatory element binding factor-1c (SREBF-1c) were found in diabetic
      sciatic nerve. Expression of myelin's major protein, myelin protein zero (P0),
      was also suppressed by diabetes. In addition, we confirmed that diabetes induces
      sciatic nerve myelin abnormalities, primarily infoldings that have previously
      been associated with altered membrane fluidity. In a diabetic setting, synthetic
      activator of the nuclear receptor liver X receptor (LXR) increased SREBF-1c
      function and restored myelin lipid species and P0 expression levels to normal.
      These LXR-modulated improvements were associated with restored myelin structure
      in sciatic nerve and enhanced performance in functional tests such as thermal
      nociceptive threshold and nerve conduction velocity. These findings demonstrate
      an important role for the LXR-SREBF-1c axis in protection from diabetes-induced
      myelin abnormalities.

PMID- 22158831
TI  - On the spontaneous carboxylation of 1-butyl-3-methylimidazolium acetate by carbon
      dioxide.
AB  - The formation of 1-butyl-3-methylimidazolium-2-carboxylate in the mixture of
      CO(2) with 1-butyl-3-methylimidazolium acetate under mild conditions (298 K, 0.1
      MPa) has been put in evidence in the liquid phase using Raman and infrared
      spectroscopy complemented by DFT calculations and NMR ((1)H, (13)C, (15)N)
      spectroscopy.

PMID- 22158832
TI  - On the analyses of fluorescence depolarisation data in the presence of electronic
      energy migration. Part I: Theory and general description.
AB  - A new and general procedure is described for a detailed analysis of time-resolved
      fluorescence depolarisation data in the presence of electronic energy migration.
      An isotropic ensemble of bifluorophoric molecules (D(1)-R-D(2)) has been studied
      to demonstrate its utility. Intramolecular donor-donor energy migration occurs
      between the two donor groups (D), which are covalently connected to a rigid
      linker group (R). These groups undergo restricted reorientational motions with
      respect to the R group. The analysis of depolarisation data basically involves
      the search for best-fit parameters which describe the local reorientational
      motions, the intermolecular D(1)-D(2) distance, as well as the mutual
      orientations of the donors. For this, the analysis is partly performed on the
      Fourier domain and the best-fit parameters are determined by using an approach
      based on a Genetic Algorithm. The energy migration process has been described by
      using Monte Carlo simulations and an extended Forster theory (EFT). It is found
      that the EFT provides the least time-consuming computational method. Since one
      photon and two-photon excited fluorescence experiments can be applied for energy
      migration studies, a general and unified theoretical formulation is given.

PMID- 22158833
TI  - Efficient conversion of CO2 and H2O into hydrocarbon fuel over ZnAl2O(4)-modified
      mesoporous ZnGaNO under visible light irradiation.
AB  - Considering light absorption by narrowing the band gap and gas capture by the
      mesostructure and basicity of material, an efficient artificial photosynthesis
      system was constructed based on a mesoporous ZnAl(2)O(4)-modified ZnGaNO
      photocatalyst.

PMID- 22158835
TI  - Signal amplification by rolling circle amplification on universal flaps yielded
      from target-specific invasive reaction.
AB  - Detection of nucleic acids with signal amplification is preferable in clinical
      diagnosis. A novel approach was developed for signal amplification by coupling
      invasive reaction with hyperbranched rolling circle amplification (HRCA).
      Invasive reaction, which does not rely on specific recognition sequences in a
      target but a specific structure formed by the specific binding of an upstream
      probe and a downstream probe to a target DNA, can generate thousands of flaps
      from one target DNA; then the flaps are ligated with padlock probes to form
      circles, which are the templates of HRCA. As HRCA amplicon sequence is free of
      target DNA sequence, signal amplification is achieved. Because flap sequence is
      the same to any target of interest, HRCA is universal; the detection cost is
      hence greatly reduced. The sensitivity of the proposed method is less than 1 fM
      artificial DNA targets; and the specificity of the method is high enough to
      discriminate one base difference in the target sequence. The feasibility was
      verified by detecting real biological samples from HBV carriers, indicating that
      the method is highly sensitive, cost-effective, and has a low risk of cross
      contamination from amplicons. These properties should give great potential in
      clinical diagnosis.

PMID- 22158834
TI  - ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over
      20:4n6 and 22:6n3.
AB  - We hypothesized that reduction/loss of very long chain PUFAs (VLC-PUFAs) due to
      mutations in the ELOngase of very long chain fatty acid-4 (ELOVL4) protein
      contributes to retinal degeneration in autosomal dominant Stargardt-like macular
      dystrophy (STGD3) and age-related macular degeneration; hence, increasing VLC
      PUFA in the retina of these patients could provide some therapeutic benefits.
      Thus, we tested the efficiency of elongation of C20-C22 PUFA by the ELOVL4
      protein to determine which substrates are the best precursors for biosynthesis of
      VLC-PUFA. The ELOVL4 protein was expressed in pheochromocytoma cells, while green
      fluorescent protein-expressing and nontransduced cells served as controls. The
      cells were treated with 20:5n3, 22:6n3, and 20:4n6, either individually or in
      equal combinations. Both transduced and control cells internalized and elongated
      the supplemented FAs to C22-C26 precursors. Only ELOVL4-expressing cells
      synthesized C28-C38 VLC-PUFA from these precursors. In general, 20:5n3 was more
      efficiently elongated to VLC-PUFA in the ELOVL4-expressing cells, regardless of
      whether it was in combination with 22:6n3 or with 20:4n6. In each FA treatment
      group, C34 and C36 VLC-PUFAs were the predominant VLC-PUFAs in the ELOVL4
      expressing cells. In summary, 20:5n3, followed by 20:4n6, seems to be the best
      precursor for boosting the synthesis of VLC-PUFA by ELOVL4 protein.

PMID- 22158836
TI  - Atomic layer deposition synthesis of platinum-tungsten carbide core-shell
      catalysts for the hydrogen evolution reaction.
AB  - Pt was deposited onto tungsten carbide powders using atomic layer deposition to
      produce core-shell catalysts for the hydrogen evolution reaction (HER). The Pt
      loading on these catalysts was reduced nearly ten-fold compared to a bulk Pt
      catalyst while equivalent HER activities were observed.

PMID- 22158837
TI  - Selective adsorption toward toxic metal ions results in selective response:
      electrochemical studies on a polypyrrole/reduced graphene oxide nanocomposite.
AB  - Highly selective adsorption of a polypyrrole/reduced graphene oxide nanocomposite
      toward Hg(2+) results in electrochemically selective detection of Hg(2+). This
      interesting finding is of practical utility compared to the biotechniques and
      surface functionalization-based methods.

PMID- 22158838
TI  - The interaction between tea polyphenols and rice starch during gelatinization.
AB  - The interaction between tea polyphenols (TPLs) and rice starch (RS) during
      gelatinization has been studied. In the RVA analysis, TPLs-fortified RS exhibited
      no clearly defined peak viscosity and hot paste viscosity. After excluding other
      factors, irregular viscosity changes were attributed to the strong interactions
      between RS and TPLs during pasting/gelatinization. Subsequently, the coupling
      constants of samples A (the gelatinized sample of the blend of 16% TPLs and RS)
      and B (the blend of 16% TPLs and gelatinized RS sample) in (1)H-NMR measurements
      were found to be the difference. Sample A had two coupling constants, (26h)J(HH)
      = 82.08, 100.77 Hz and (6h)J(HH) = 35.57 Hz, whereas Sample B had one larger
      coupling constant, (9h)J(HH) = 140.24 Hz. This implied that these two samples
      differed in H-H interaction and interaction strength of sample A may be stronger
      than that of sample B. More important is, sample A had clearly broadened O-H
      stretching and frequency red-shifts of C-O-H bending as compared with sample B in
      quantitative FT-IR analysis. The overall results indicate that TPLs and RS can
      have hydrogen bonding interaction during gelatinization.

PMID- 22158839
TI  - Microbial diversity affects self-organization of the soil-microbe system with
      consequences for function.
AB  - Soils are complex ecosystems and the pore-scale physical structure regulates key
      processes that support terrestrial life. These include maintaining an appropriate
      mixture of air and water in soil, nutrient cycling and carbon sequestration.
      There is evidence that this structure is not random, although the organizing
      mechanism is not known. Using X-ray microtomography and controlled microcosms, we
      provide evidence that organization of pore-scale structure arises spontaneously
      out of the interaction between microbial activity, particle aggregation and
      resource flows in soil. A simple computational model shows that these
      interactions give rise to self-organization involving both physical particles and
      microbes that gives soil unique material properties. The consequence of self
      organization for the functioning of soil is determined using lattice Boltzmann
      simulation of fluid flow through the observed structures, and predicts that the
      resultant micro-structural changes can significantly increase hydraulic
      conductivity. Manipulation of the diversity of the microbial community reveals a
      link between the measured change in micro-porosity and the ratio of fungal to
      bacterial biomass. We suggest that this behaviour may play an important role in
      the way that soil responds to management and climatic change, but that this
      capacity for self-organization has limits.

PMID- 22158840
TI  - Impact of release dynamics of laser-irradiated polymer micropallets on the
      viability of selected adherent cells.
AB  - We use time-resolved interferometry, fluorescence assays and computational fluid
      dynamics (CFD) simulations to examine the viability of confluent adherent cell
      monolayers to selection via laser microbeam release of photoresist polymer
      micropallets. We demonstrate the importance of laser microbeam pulse energy and
      focal volume position relative to the glass-pallet interface in governing the
      threshold energies for pallet release as well as the pallet release dynamics.
      Measurements using time-resolved interferometry show that increases in laser
      pulse energy result in increasing pallet release velocities that can approach 10
      m s(-1) through aqueous media. CFD simulations reveal that the pallet motion
      results in cellular exposure to transient hydrodynamic shear stress amplitudes
      that can exceed 100 kPa on microsecond timescales, and which produces reduced
      cell viability. Moreover, CFD simulation results show that the maximum shear
      stress on the pallet surface varies spatially, with the largest shear stresses
      occurring on the pallet periphery. Cell viability of confluent cell monolayers on
      the pallet surface confirms that the use of larger pulse energies results in
      increased rates of necrosis for those cells situated away from the pallet centre,
      while cells situated at the pallet centre remain viable. Nevertheless,
      experiments that examine the viability of these cell monolayers following pallet
      release show that proper choices for laser microbeam pulse energy and focal
      volume position lead to the routine achievement of cell viability in excess of 90
      per cent. These laser microbeam parameters result in maximum pallet release
      velocities below 6 m s(-1) and cellular exposure of transient hydrodynamic shear
      stresses below 20 kPa. Collectively, these results provide a mechanistic
      understanding that relates pallet release dynamics and associated transient shear
      stresses with subsequent cellular viability. This provides a quantitative,
      mechanistic basis for determining optimal operating conditions for laser
      microbeam-based pallet release systems for the isolation and selection of
      adherent cells.

PMID- 22158841
TI  - Contributions of talin-1 to glioma cell-matrix tensional homeostasis.
AB  - The ability of cells to adapt their mechanical properties to those of the
      surrounding microenvironment (tensional homeostasis) has been implicated in the
      progression of a variety of solid tumours, including the brain tumour
      glioblastoma multiforme (GBM). GBM tumour cells are highly sensitive to
      extracellular matrix (ECM) stiffness and overexpress a variety of focal adhesion
      proteins, such as talin. While talin has been shown to play critical early roles
      in integrin-based force-sensing in non-tumour cells, it remains unclear whether
      this protein contributes to tensional homeostasis in GBM cells. Here, we
      investigate the role of the talin isoform talin-1 in enabling human GBM cells to
      adapt to ECM stiffness. We show that human GBM cells express talin-1, and we use
      RNA interference to suppress talin-1 expression without affecting levels of talin
      2, vinculin or phosphorylated focal adhesion kinase. Knockdown of talin-1
      strongly reduces both cell spreading area and random migration speed but does not
      significantly affect overall focal adhesion size distributions. Most strikingly,
      atomic force microscopy indentation reveals that talin-1 suppression compromises
      adaptation of cell stiffness to changes in ECM stiffness. Together, these data
      support a role for talin-1 in the maintenance of tensional homeostasis in GBM and
      suggest a functional role for enriched talin expression in this tumour.

PMID- 22158842
TI  - Optimized nanoscale composite behaviour in limpet teeth.
AB  - Limpet teeth are striking examples of a biological fibrous nanocomposite
      consisting of goethite mineral within a polymeric chitin matrix. The mechanical
      function of limpet teeth is critically dependent on the efficient composite
      behaviour of goethite, formed as distinct discontinuous nanofibres, reinforcing
      the matrix. The mechanical properties of discrete volumes from a limpet tooth
      measured using atomic force microscopy indicate how the tooth structure can be
      approximated as a short fibre-reinforced composite. Short fibre composite
      analysis reveals how the goethite nanofibres have a length optimized for the
      transfer of stress from the matrix to fibre and highlight how this limpet tooth
      structure is efficient in a mechanical load-bearing function.

PMID- 22158844
TI  - Patient reported outcomes and their importance in the development of novel
      surgical techniques.
AB  - INTRODUCTION: Although traditional quality measures such as morbidity and
      mortality outcomes still pay an important role in the assessment of health care
      quality, greater emphasis is now being placed on patient-reported outcome
      measures such as patient satisfaction. This area is especially important for
      novel surgical technologies such as single-incision laparoscopic surgery (SILS)
      and natural orifice translumenal endoscopic surgery (NOTES). These new
      innovations are able to minimize or abolish surgical scarring and are likely to
      have most benefit in the area of patient satisfaction as opposed to traditional
      outcome measures. Therefore, it is important to gauge the public opinion
      regarding these new techniques, as continued public interest can help support
      further research in this up-and-coming field. METHODS: A questionnaire study was
      carried out with members of the general public. Questions were asked regarding
      preference for surgical techniques, including open surgery, laparoscopic surgery,
      NOTES, and SILS, in the situation of acute appendicitis. RESULTS: The
      questionnaire was completed by 1006 individuals. Results indicated that an
      established safety profile was necessary before the introduction of these new
      techniques into general practice. The concept of scarless surgery did appeal to
      the public, with SILS being the treatment of choice in the scenario of acute
      appendicitis. DISCUSSION: The patient perspective on health care is an important
      aspect of health care quality assessment. This is especially important with
      regard to the development of novel surgical techniques such as SILS and NOTES.
      With these techniques, the potential benefits are most likely to be found in the
      realms of reduced scarring and improved patient satisfaction. The findings from
      this study demonstrate the public's interest in these new techniques and thus
      give further support to continued research and development in this area.

PMID- 22158845
TI  - Evaluation of bioabsorbable seamguard for staple line reinforcement in stapled
      rectal anastomoses.
AB  - INTRODUCTION: The concept of staple line reinforcement is a growing area of
      interest. This study evaluated the feasibility and effect of using bioabsorbable
      Seamguard (BSG) to bolster end-to-end stapled rectal anastomoses in a porcine
      model. METHODS: Eleven female 45-kg Yucatan domestic pigs were used. Each animal
      served as its own control by creating a BSG and nonreinforced anastomosis using a
      29-mm end-to-end anastomotic stapling device. Reinforced anastomoses were
      randomized to proximal and distal positions along the rectum. Each staple line
      reinforcement agent consisted of adding BSG to the stapling device according to
      the manufacturer's instructions. Barium enemas were then performed and the 2
      anastomotic sites harvested. Each anastomosis underwent burst testing. The
      internal diameter of each anastomosis was measured and underwent pathologic
      review. RESULTS: Bolstered anastomoses offered no strength advantage as burst
      pressures were no different as compared with unbolstered anastomoses. There was
      also no difference in anastomotic internal or external diameters. Only 1 stapled
      anastomosis burst during testing and none in the bolstered group. On histological
      analysis, there was a significant increase in inflammatory infiltrate in the
      bolstered group as compared with the stapled group (P = .041), with a higher
      incidence of lymphocytes (P = .047) and giant cells (P = .037). There was no
      difference in mucosal loss at the anastomotic site, neovascularization,
      fibroblast presence, extent of fibrosis, muscle layer disruption, percentage of
      anastomosis replaced by collagen, and elastin deposition. CONCLUSIONS: The
      routine use of BSG bolsters in stapled rectal anastomoses is safe and results in
      equivalent anastomotic strength as traditional stapled anastomoses.

PMID- 22158846
TI  - Five genome sequences of subspecies B1 human adenoviruses associated with acute
      respiratory disease.
AB  - Five genomes of human subspecies B1 adenoviruses isolated from cases of acute
      respiratory disease have been sequenced and archived for reference. These include
      representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and
      HAdV-7d2. The other three are HAdV-3/16, HAdV-16 strain E26, and HAdV-3+7 strain
      Takeuchi. All are recombinant genomes. Genomics and bioinformatics provide
      detailed views into the genetic makeup of these pathogens and insight into their
      molecular evolution. Retrospective characterization of particularly problematic
      older pathogens such as HAdV-7h (1987) and intriguing isolates such as HAdV-3+7
      strain Takeuchi (1958) may provide clues to their phenotypes and serology and may
      suggest protocols for prevention and treatment.

PMID- 22158847
TI  - Complete genome sequence of Bacillus cereus bacteriophage BCP78.
AB  - Bacillus cereus is generally found in soil habitats, and it contaminates a wide
      variety of foods, causing food poisoning with symptoms such as vomiting and
      diarrhea. To develop a novel biocontrol agent to inhibit this pathogen,
      bacteriophage BCP78 belonging to the Siphoviridae family was isolated from a
      fermented food sample. Here we announce the complete genome sequence of BCP78,
      which may be useful for understanding its inhibition mechanism against B. cereus,
      and describe major findings from the genome annotation.

PMID- 22158843
TI  - Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview
      of their biological applications and strategies for new developments.
AB  - This article provides an overview on the application of metallic ions in the
      fields of regenerative medicine and tissue engineering, focusing on their
      therapeutic applications and the need to design strategies for controlling the
      release of loaded ions from biomaterial scaffolds. A detailed summary of relevant
      metallic ions with potential use in tissue engineering approaches is presented.
      Remaining challenges in the field and directions for future research efforts with
      focus on the key variables needed to be taken into account when considering the
      controlled release of metallic ions in tissue engineering therapeutics are also
      highlighted.

PMID- 22158848
TI  - Complete genome sequence of a novel porcine circovirus-like agent.
AB  - We report here the genome sequence of a porcine circovirus-like agent. The
      sequenced genome of this porcine circovirus-like agent is composed of a 648
      nucleotide circular DNA that includes three predicted protein-coding genes, which
      means the agent should be a novel member of the family Circoviridae.

PMID- 22158849
TI  - Is the T-wave alternans magnitude in apparently healthy subjects and in different
      subsets of patients with ischaemic heart disease T-wave amplitude dependent?

PMID- 22158850
TI  - Is the coexistence of sustained ST-segment elevation and abnormal Q waves a risk
      factor for electrical storm in implanted cardioverter defibrillator patients with
      structural heart diseases?
AB  - AIM: The aim of this study was to determine whether or not the coexistence of
      sustained ST-segment elevation and abnormal Q waves (STe-Q) could be a risk
      factor for electrical storm (ES) in implanted cardioverter defibrillator (ICD)
      patients with structural heart diseases. METHODS AND RESULTS: In all, 156
      consecutive patients received ICD therapy for secondary prevention of sudden
      cardiac death and/or sustained ventricular tachyarrhythmias were included.
      Electrical storm was defined as >=3 separate episodes of ventricular tachycardia
      (VT) and/or ventricular fibrillation (VF) terminated by ICD therapies within 24
      h. During a mean follow-up of 1825 +/- 1188 days, 42 (26.9%) patients experienced
      ES, of whom 12 had coronary artery disease, 15 had idiopathic dilated
      cardiomyopathy, 6 had hypertrophic cardiomyopathy, 4 had arrhythmogenic right
      ventricular cardiomyopathy, 4 had cardiac sarcoidosis, and 1 had valvular heart
      disease. Sustained ST-segment elevation and abnormal Q waves in >=2 leads on the
      12-lead electrocardiography was observed in 33 (21%) patients. On the Kaplan
      Meier analysis, patients with STe-Q had a markedly higher risk of ES than those
      without STe-Q (P< 0.0001). The multivariate Cox proportional hazards regression
      model indicated that STe-Q and left ventricular ejection fraction (LVEF) (<30%)
      were independent risk factors associated with the recurrence of VT/VF (STe-Q: HR
      1.962, 95% CI 1.24-3.12, P= 0.004; LVEF: HR 1.860, 95% CI 1.20-2.89, P= 0.006),
      and STe-Q was an independent risk factor associated with ES (HR 4.955, 95% CI
      2.69-9.13, P< 0.0001). CONCLUSION: Sustained ST-segment elevation and abnormal Q
      waves could be a risk factor of not only recurrent VT/VF but also ES in patients
      with structural heart diseases.

PMID- 22158852
TI  - A multiplex lectin-channel monitoring method for human serum glycoproteins by
      quantitative mass spectrometry.
AB  - A mass profiling method and multiple reaction monitoring (MRM)-based quantitative
      approach were used to analyze multiple lectin-captured fractions of human serum
      using different lectins such as aleuria aurantia lectin (AAL), phytohemagglutinin
      L(4) (L-PHA), concanavalin A (Con A), and Datura stramonium agglutinin (DSA) to
      quantitatively monitor protein glycosylation diversity. Each fraction, prepared
      by multiple lectin-fractionation and tryptic digestion, was analyzed by 1-D LC
      MS/MS. Semi-quantitative profiling showed that the list of glycoproteins
      identified from each lectin-captured fraction is significantly different
      according to the used lectin. Thus, it was confirmed that the multiplex lectin
      channel monitoring (LCM) using multiple lectins is useful for investigating
      protein glycosylation diversity in a proteome sample. Based on the semi
      quantitative mass profiling, target proteins showing lectin-specificity among
      each lectin-captured fraction were selected and analyzed by the MRM-based method
      in triplicate using each lectin-captured fraction (average CV 7.9%). The MRM
      based analysis for each lectin-captured fraction was similar to those obtained by
      the profiling experiments. The abundance of each target protein measured varied
      dramatically, based on the lectin-specificity. The multiplex LCM approach using
      MRM-based analyses is useful for quantitatively monitoring target protein
      glycoforms selectively fractionated by multiple lectins. Thus through multiplex
      LCM rather than single, we could inquire minutely into protein glycosylation
      states.

PMID- 22158853
TI  - The coordination and polymerisation of cyclic 1,3-dienes by gold(I) cations.
AB  - Cyclopentadiene and 1,3-cyclohexadiene are readily polymerised by [LAu][X]. With
      specific ancillary ligands polymerisation was suppressed and a molecular species
      involving an Au(I) cation eta(2)-bonding CpH was isolated and whose structure was
      probed in both the solid state and in solution.

PMID- 22158854
TI  - The need to belong and symptoms of acute physical health in early adolescence.
AB  - This study examined the role of social belonging and self-esteem in acute
      physical health and mood in 159 young adolescents (aged 11 to 14 years).
      Standardized self-report measures of belongingness (school, home and community),
      self-esteem, acute physical symptoms, and affect, were completed for the previous
      month. Higher levels of inclusive belonging were associated with fewer physical
      symptoms and better affect. Domain specific belonging was independently linked to
      acute physical symptoms and level of affect, with pathways between belonging and
      outcome mediated by self-esteem. Findings emphasize the need for greater
      recognition of the role of belonging in physical health outcomes.

PMID- 22158855
TI  - 8R-Lipoxygenase-catalyzed synthesis of a prominent cis-epoxyalcohol from dihomo
      gamma-linolenic acid: a distinctive transformation compared with S-lipoxygenases.
AB  - Conversion of fatty acid hydroperoxides to epoxyalcohols is a well known
      secondary reaction of lipoxygenases, described for S-specific lipoxygenases
      forming epoxyalcohols with a trans-epoxide configuration. Here we report on R
      specific lipoxygenase synthesis of a cis-epoxyalcohol. Although arachidonic and
      dihomo-gamma-linolenic acids are metabolized by extracts of the Caribbean coral
      Plexaura homomalla via 8R-lipoxygenase and allene oxide synthase activities,
      20:3omega6 forms an additional prominent product, identified using UV, GC-MS, and
      NMR in comparison to synthetic standards as 8R,9S-cis-epoxy-10S-erythro-hydroxy
      eicosa-11Z,14Z-dienoic acid. Both oxygens of (18)O-labeled 8R-hydroperoxide are
      retained in the product, indicating a hydroperoxide isomerase activity.
      Recombinant allene oxide synthase formed only allene epoxide from 8R-hydroperoxy
      20:3omega6, whereas two different 8R-lipoxygenases selectively produced the
      epoxyalcohol.A biosynthetic scheme is proposed in which a partial rotation of the
      reacting intermediate is required to give the observed erythro epoxyalcohol
      product. This characteristic and the synthesis of cis-epoxy epoxyalcohol may be a
      feature of R-specific lipoxygenases.

PMID- 22158858
TI  - 3Rs of animal testing for regenerative medicine products.
AB  - Considerations of animal welfare have spurred the design of "smarter" preclinical
      studies intended to ultimately benefit patients.

PMID- 22158856
TI  - Metronomic dosing of BH3 mimetic small molecule yields robust antiangiogenic and
      antitumor effects.
AB  - Bcl-2 is an antiapoptotic protein that has also been found to function as a
      proangiogenic signaling molecule. Improvements in antiangiogenic therapy can be
      engendered by metronomic dosing. Thus, we hypothesized that BH3-mimetic drugs
      that antagonize Bcl-2 family proteins may exert a greater efficacy when dosed
      metronomically. To examine this hypothesis, we employed AT101, an orally
      available and well-tolerated BH3-mimetic drug that has been established as
      effective. In a mouse xenograft model of human squamous cell carcinomas (SCC)
      that includes a humanized vasculature, we explored the effects of docetaxel in
      combination with either daily (metronomic) or weekly (bolus) doses of AT101. In
      addition, we explored the effect of single or combination therapy on angiogenesis
      and survival of endothelial or SCC cells in vitro. Metronomic AT101 therapy
      increased mouse survival, decreased tumor mitotic index, and decreased tumor
      microvessel density, compared with bolus therapy. Therapeutic potentiation was
      achieved by similar overall drug exposure and without altering systemic
      toxicities. Combinations of AT101 and docetaxel produced additive toxicity in
      both endothelial and SCC tumor cells. Notably, subapoptotic concentrations of
      AT101 potently inhibited the angiogenic potential of endothelial cells. Taken
      together, our findings unveil the efficacious benefits that can be achieved by
      metronomic delivery of BH3-mimetic drugs, in particular suggesting that SCC
      patients with might benefit from low-dose continuous administration of these
      drugs.

PMID- 22158859
TI  - ROCK in a stiff place.
AB  - Understanding the molecular and cellular mechanisms involved in the progression
      of atherosclerosis has revealed a vital role for the Rho kinase (ROCK) pathway
      associated with stiffening of the underlying extracellular matrix (Huynh et al.,
      this issue).

PMID- 22158860
TI  - Age-related intimal stiffening enhances endothelial permeability and leukocyte
      transmigration.
AB  - Age is the most significant risk factor for atherosclerosis; however, the link
      between age and atherosclerosis is poorly understood. During both aging and
      atherosclerosis progression, the blood vessel wall stiffens owing to alterations
      in the extracellular matrix. Using in vitro and ex vivo models of vessel wall
      stiffness and aging, we show that stiffening of extracellular matrix within the
      intima promotes endothelial cell permeability--a hallmark of atherogenesis. When
      cultured on hydrogels fabricated to match the elasticity of young and aging
      intima, endothelial monolayers exhibit increased permeability and disrupted cell
      cell junctions on stiffer matrices. In parallel experiments, we showed a
      corresponding increase in cell-cell junction width with age in ex vivo aortas
      from young (10 weeks) and old (21 to 25 months) healthy mice. To investigate the
      mechanism by which matrix stiffening alters monolayer integrity, we found that
      cell contractility increases with increased matrix stiffness, mechanically
      destabilizing cell-cell junctions. This increase in endothelial permeability
      results in increased leukocyte extravasation, which is a critical step in
      atherosclerotic plaque formation. Mild inhibition of Rho-dependent cell
      contractility using Y-27632, an inhibitor of Rho-associated kinase, or small
      interfering RNA restored monolayer integrity in vitro and in vivo. Our results
      suggest that extracellular matrix stiffening alone, which occurs during aging,
      can lead to endothelial monolayer disruption and atherosclerosis pathogenesis.
      Because previous therapeutics designed to decrease vascular stiffness have been
      met with limited success, our findings could be the basis for the design of
      therapeutics that target the Rho-dependent cellular contractile response to
      matrix stiffening, rather than stiffness itself, to more effectively prevent
      atherosclerosis progression.

PMID- 22158861
TI  - Penetration of tenofovir and emtricitabine in mucosal tissues: implications for
      prevention of HIV-1 transmission.
AB  - A mainstay of strategies to prevent HIV-1 transmission is to use antiretroviral
      therapy (ART) for pre-exposure prophylaxis (PrEP). Critical to the design and
      interpretation of PrEP prevention trials is the ability to make accurate
      pharmacological measurements of ART drugs in human genital and colorectal mucosal
      tissues, the principal route of HIV transmission. Here, we evaluated two drugs
      that are preferentially used for PrEP: tenofovir (TFV) disoproxil fumarate (TDF)
      and emtricitabine (FTC). A single oral dose of TDF/FTC (Truvada) was administered
      to 15 healthy individuals. Over the next 14 days, TFV and FTC were measured in
      blood plasma and genital secretions using a sensitive assay (lower level of
      quantification, 0.1 ng/ml). The active intracellular phosphorylated metabolites
      of these drugs [TFV diphospate (TFV-DP) and FTC triphosphate (FTC-TP)] were
      measured in homogenates prepared from rectal, vaginal, and cervical tissues. TFV
      and FTC were detected in blood plasma 14 days after administration of a single
      dose. The area under the concentration-time curve from 24 hours to 14 days (AUC(1
      14d)) for FTC in genital secretions was 27-fold greater than in blood plasma,
      whereas the AUC(1-14d) for TFV was only 2.5-fold greater in genital secretions
      than in blood plasma. In rectal tissue, TFV and TFV-DP concentrations were
      detectable for 14 days and were 100-fold higher than the concentrations in
      vaginal and cervical tissues. Vaginal and cervical tissue concentrations of FTC
      were 10- to 15-fold higher than in rectal tissue. Despite high concentrations of
      FTC in vaginal and cervical tissue, FTC-TP concentrations in all tissue types
      were detected for only 2 days after dose. The exposure to TFV, TFV-DP, FTC, and
      FTC-TP was wide ranging depending on the type of mucosal tissue. These results
      demonstrate the need for detailed pharmacological studies to improve the
      application of ART for PrEP to prevent transmission of HIV.

PMID- 22158862
TI  - Large putative PEST-like sequence motif at the carboxyl tail of human calcium
      receptor directs lysosomal degradation and regulates cell surface receptor level.
AB  - A deletion between amino acid residues Ser(895) and Val(1075) in the carboxyl
      terminus of the human calcium receptor (hCaR), which causes autosomal dominant
      hypocalcemia, showed enhanced signaling activity and increased cell surface
      expression in HEK293 cells (Lienhardt, A., Garabedian, M. G., Bai, M., Sinding,
      C., Zhang, Z., Lagarde, J. P., Boulesteix, J., Rigaud, M., Brown, E. M., and
      Kottler, M. L. (2000) J. Clin. Endocrinol. Metab. 85, 1695-1702). To identify the
      underlying mechanism(s) for these increases, we investigated the effects of
      carboxyl tail truncation and deletion in hCaR mutants using a combination of
      biochemical and cell imaging approaches to define motifs that participate in
      regulating cell surface numbers of this G protein-coupled receptor. Our data
      indicate a rapid constitutive receptor internalization of the cell surface hCaR,
      accumulating in early (Rab7 positive) and late endosomal (LAMP1 positive) sorting
      compartments, before targeting to lysosomes for degradation. Recycling of hCaR
      back to the cell surface was also evident. Truncation and deletion mapping
      defined a 51-amino acid sequence between residues 920 and 970 that is required
      for targeting to lysosomes and degradation but not for internalization or
      recycling of the receptor. No singular sequence motif was identified, instead the
      required sequence elements seem to distribute throughout this entire interval.
      This interval includes a high proportion of acidic and hydroxylated amino acid
      residues, suggesting a similarity to PEST-like degradation motif (PESTfind score
      of +10) and several glutamine repeats. The results define a novel large PEST-like
      sequence that participates in the sorting of internalized hCaR routed to the
      lysosomal/degradation pathway that regulates cell surface receptor numbers.

PMID- 22158863
TI  - Beltless translocation domain of botulinum neurotoxin A embodies a minimum ion
      conductive channel.
AB  - Botulinum neurotoxin, the causative agent of the paralytic disease botulism, is
      an endopeptidase composed of a catalytic domain (or light chain (LC)) and a heavy
      chain (HC) encompassing the translocation domain (TD) and receptor-binding
      domain. Upon receptor-mediated endocytosis, the LC and TD are proposed to undergo
      conformational changes in the acidic endocytic environment resulting in the
      formation of an LC protein-conducting TD channel. The mechanism of channel
      formation and the conformational changes in the toxin upon acidification are
      important but less well understood aspects of botulinum neurotoxin intoxication.
      Here, we have identified a minimum channel-forming truncation of the TD, the
      "beltless" TD, that forms transmembrane channels with ion conduction properties
      similar to those of the full-length TD. At variance with the holotoxin and the
      HC, channel formation for both the TD and the beltless TD occurs independent of a
      transmembrane pH gradient. Furthermore, acidification in solution induces
      moderate secondary structure changes. The subtle nature of the conformational
      changes evoked by acidification on the TD suggests that, in the context of the
      holotoxin, larger structural rearrangements and LC unfolding occur preceding or
      concurrent to channel formation. This notion is consistent with the hypothesis
      that although each domain of the holotoxin functions individually, each domain
      serves as a chaperone for the others.

PMID- 22158864
TI  - Human umbilical cord blood cells protect oligodendrocytes from brain ischemia
      through Akt signal transduction.
AB  - Human umbilical cord blood (HUCB) cells protect the brain against ischemic
      injury, yet the mechanism of protection remains unclear. Using both in vitro and
      in vivo paradigms, this study examined the role of Akt signaling and
      peroxiredoxin 4 expression in human umbilical cord blood cell-mediated protection
      of oligodendrocytes from ischemic conditions. As previously reported, the
      addition of HUCB cells to oligodendrocyte cultures prior to oxygen glucose
      deprivation significantly enhanced oligodendrocyte survival. The presence of
      human umbilical cord blood cells also increased Akt phosphorylation and elevated
      peroxiredoxin 4 expression in oligodendrocytes. Blocking either Akt or
      peroxiredoxin 4 activity with Akt Inhibitor IV or a peroxiredoxin 4-neutralizing
      antibody, respectively, negated the protective effects of human umbilical cord
      blood cells. In vivo, systemic administration of human umbilical cord blood cells
      48 h after middle cerebral artery occlusion increased Akt phosphorylation and
      peroxiredoxin 4 protein expression while reducing proteolytic cleavage of caspase
      3 in oligodendrocytes residing in the ipsilateral external capsule. Moreover,
      human umbilical cord blood cells protected striatal white matter bundles from
      degeneration following middle cerebral artery occlusion. These results suggest
      that the soluble factors released from human umbilical cord blood cells converge
      on Akt to elevate peroxiredoxin 4 levels, and these effects contribute to
      oligodendrocyte survival.

PMID- 22158865
TI  - Enhanced killing of cancer cells by poly(ADP-ribose) polymerase inhibitors and
      topoisomerase I inhibitors reflects poisoning of both enzymes.
AB  - Poly(ADP-ribose) polymerase-1 (PARP1) plays critical roles in the regulation of
      DNA repair. Accordingly, small molecule inhibitors of PARP are being developed as
      agents that could modulate the activity of genotoxic chemotherapy, such as
      topoisomerase I poisons. In this study we evaluated the ability of the PARP
      inhibitor veliparib to enhance the cytotoxicity of the topoisomerase I poisons
      topotecan and camptothecin (CPT). Veliparib increased the cell cycle and
      cytotoxic effects of topotecan in multiple cell line models. Importantly, this
      sensitization occurred at veliparib concentrations far below those required to
      substantially inhibit poly(ADP-ribose) polymer synthesis and at least an order of
      magnitude lower than those involved in selective killing of homologous
      recombination-deficient cells. Further studies demonstrated that veliparib
      enhanced the effects of CPT in wild-type mouse embryonic fibroblasts (MEFs) but
      not Parp1(-/-) MEFs, confirming that PARP1 is the critical target for this
      sensitization. Importantly, parental and Parp1(-/-) MEFs had indistinguishable
      CPT sensitivities, ruling out models in which PARP1 catalytic activity plays a
      role in protecting cells from topoisomerase I poisons. To the contrary, cells
      were sensitized to CPT in a veliparib-independent manner upon transfection with
      PARP1 E988K, which lacks catalytic activity, or the isolated PARP1 DNA binding
      domain. These results are consistent with a model in which small molecule
      inhibitors convert PARP1 into a protein that potentiates the effects of
      topoisomerase I poisons by binding to damaged DNA and preventing its normal
      repair.

PMID- 22158866
TI  - Inhibition of insulin signaling in endothelial cells by protein kinase C-induced
      phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K).
AB  - The regulation of endothelial function by insulin is consistently abnormal in
      insulin-resistant states and diabetes. Protein kinase C (PKC) activation has been
      reported to inhibit insulin signaling selectively in endothelial cells via the
      insulin receptor substrate/PI3K/Akt pathway to reduce the activation of
      endothelial nitric-oxide synthase (eNOS). In this study, it was observed that PKC
      activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2)
      signaling of insulin's activation of PI3K/eNOS by decreasing only tyrosine
      phosphorylation of IRS2. In addition, PKC activation, by general activator and
      specifically by angiotensin II, increased the phosphorylation of p85/PI3K, which
      decreases its association with IRS1 and activation. Thr-86 of p85/PI3K was
      identified to be phosphorylated by PKC activation and confirmed to affect IRS1
      mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of
      the Thr-86 region of p85/PI3K. Thus, PKC and angiotensin-induced phosphorylation
      of Thr-86 of p85/PI3K may partially inhibit the activation of PI3K/eNOS by
      multiple cytokines and contribute to endothelial dysfunction in metabolic
      disorders.

PMID- 22158867
TI  - Increased angiogenesis protects against adipose hypoxia and fibrosis in metabolic
      disease-resistant 11beta-hydroxysteroid dehydrogenase type 1 (HSD1)-deficient
      mice.
AB  - In obesity, rapidly expanding adipose tissue becomes hypoxic, precipitating
      inflammation, fibrosis, and insulin resistance. Compensatory angiogenesis may
      prevent these events. Mice lacking the intracellular glucocorticoid-amplifying
      enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1(-/-)) have
      "healthier" adipose tissue distribution and resist metabolic disease with diet
      induced obesity. Here we show that adipose tissues of 11betaHSD1(-/-) mice
      exhibit attenuated hypoxia, induction of hypoxia-inducible factor (HIF-1alpha)
      activation of the TGF-beta/Smad3/alpha-smooth muscle actin (alpha-SMA) signaling
      pathway, and fibrogenesis despite similar fat accretion with diet-induced
      obesity. Moreover, augmented 11betaHSD1(-/-) adipose tissue angiogenesis is
      associated with enhanced peroxisome proliferator-activated receptor gamma
      (PPARgamma)-inducible expression of the potent angiogenic factors VEGF-A, apelin,
      and angiopoietin-like protein 4. Improved adipose angiogenesis and reduced
      fibrosis provide a novel mechanism whereby suppression of intracellular
      glucocorticoid regeneration promotes safer fat expansion with weight gain.

PMID- 22158869
TI  - Phospholipase Cgamma-2 and intracellular calcium are required for
      lipopolysaccharide-induced Toll-like receptor 4 (TLR4) endocytosis and interferon
      regulatory factor 3 (IRF3) activation.
AB  - Toll-like receptor 4 (TLR4) is unique among the TLRs in its use of multiple
      adaptor proteins leading to activation of both the interferon regulatory factor 3
      (IRF3) and nuclear factor kappaB (NF-kappaB) pathways. Previous work has
      demonstrated that TLR4 initiates NF-kappaB activation from the plasma membrane,
      but that subsequent TLR4 translocation to the endosomes is required for IRF3
      activation. Here we have characterized several components of the signaling
      pathway that governs TLR4 translocation and subsequent IRF3 activation. We find
      that phospholipase C gamma2 (PLCgamma2) accounts for LPS-induced inositol 1,4,5
      trisphosphate (IP(3)) production and subsequent calcium (Ca(2+)) release.
      Blockage of PLCgamma2 function by inhibitors or knockdown of PLCgamma2 expression
      by siRNAs in RAW 264.7 macrophages lead to reduced IRF3, but enhanced NF-kappaB
      activation. In addition, bone marrow-derived macrophages from PLCgamma2-deficient
      mice showed impaired IRF3 phosphorylation and expression of IRF3-regulated genes
      after LPS stimulation. Using cell fractionation, we show that PLCgamma2-IP(3)
      Ca(2+) signaling cascade is required for TLR4 endocytosis following LPS
      stimulation. In conclusion, our results describe a novel role of the PLCgamma2
      IP(3)-Ca(2+) cascade in the LPS-induced innate immune response pathway where
      release of intracellular Ca(2+) mediates TLR4 trafficking and subsequent
      activation of IRF3.

PMID- 22158868
TI  - Small molecule structure correctors abolish detrimental effects of apolipoprotein
      E4 in cultured neurons.
AB  - Apolipoprotein E4 (apoE4), the major genetic risk factor for late onset Alzheimer
      disease, assumes a pathological conformation, intramolecular domain interaction.
      ApoE4 domain interaction mediates the detrimental effects of apoE4, including
      decreased mitochondrial cytochrome c oxidase subunit 1 levels, reduced
      mitochondrial motility, and reduced neurite outgrowth in vitro. Mutant apoE4
      (apoE4-R61T) lacks domain interaction, behaves like apoE3, and does not cause
      detrimental effects. To identify small molecules that inhibit domain interaction
      (i.e. structure correctors) and reverse the apoE4 detrimental effects, we
      established a high throughput cell-based FRET primary assay that determines apoE4
      domain interaction and secondary cell- and function-based assays. Screening a
      ChemBridge library with the FRET assay identified CB9032258 (a phthalazinone
      derivative), which inhibits domain interaction in neuronal cells. In secondary
      functional assays, CB9032258 restored mitochondrial cytochrome c oxidase subunit
      1 levels and rescued impairments of mitochondrial motility and neurite outgrowth
      in apoE4-expressing neuronal cells. These benefits were apoE4-specific and dose
      dependent. Modifying CB9032258 yielded well defined structure-activity
      relationships and more active compounds with enhanced potencies in the FRET assay
      (IC(50) of 23 and 116 nm, respectively). These compounds efficiently restored
      functional activities of apoE4-expressing cells in secondary assays. An EPR
      binding assay showed that the apoE4 structure correction resulted from direct
      interaction of a phthalazinone. With these data, a six-feature pharmacophore
      model was constructed for future drug design. Our results serve as a proof of
      concept that pharmacological intervention with apoE4 structure correctors negates
      apoE4 detrimental effects in neuronal cells and could be further developed as an
      Alzheimer disease therapeutic.

PMID- 22158870
TI  - Effect of PhoP-PhoQ activation by broad repertoire of antimicrobial peptides on
      bacterial resistance.
AB  - Pathogenic bacteria can resist their microenvironment by changing the expression
      of virulence genes. In Salmonella typhimurium, some of these genes are controlled
      by the two-component system PhoP-PhoQ. Studies have shown that activation of the
      system by cationic antimicrobial peptides (AMPs) results, among other changes, in
      outer membrane remodeling. However, it is not fully clear what characteristics of
      AMPs are required to activate the PhoP-PhoQ system and whether activation can
      induce resistance to the various AMPs. For that purpose, we investigated the
      ability of a broad repertoire of AMPs to traverse the inner membrane, to activate
      the PhoP-PhoQ system, and to induce bacterial resistance. The AMPs differ in
      length, composition, and net positive charge, and the tested bacteria include two
      wild-type (WT) Salmonella strains and their corresponding PhoP-PhoQ knock-out
      mutants. A lacZ-reporting system was adapted to follow PhoP-PhoQ activation. The
      data revealed that: (i) a good correlation exists among the extent of the
      positive charge, hydrophobicity, and amphipathicity of an AMP and its potency to
      activate PhoP-PhoQ; (ii) a +1 charged peptide containing histidines was highly
      potent, suggesting the existence of an additional mechanism independent of the
      peptide charge; (iii) the WT bacteria are more resistant to AMPs that are potent
      activators of PhoP-PhoQ; (iv) only a subset of AMPs, independent of their potency
      to activate the system, is more toxic to the mutated bacteria compared with the
      WT strains; and (v) short term exposure of WT bacteria to these AMPs does not
      enhance resistance. Overall, this study advances our understanding of the
      molecular mechanism by which AMPs activate PhoP-PhoQ and induce bacterial
      resistance. It also reveals that some AMPs can overcome such a resistance
      mechanism.

PMID- 22158871
TI  - Novel regulation of fibroblast growth factor 2 (FGF2)-mediated cell growth by
      polysialic acid.
AB  - Polysialic acid (polySia) is a unique polysaccharide that modifies neural cell
      adhesion molecule (NCAM) spatiotemporally. Recently, we demonstrated that polySia
      functions as a reservoir for several neurotrophic factors and neurotransmitters.
      Here, we showed the direct interaction between polySia and fibroblast growth
      factor-2 (FGF2) by native-PAGE, gel filtration, and surface plasmon resonance.
      The minimum chain length of polySia required for the interaction with FGF2 was
      17. Compared with heparan sulfate, a well known glycosaminoglycan capable of
      forming a complex with FGF2, polySia formed a larger complex with distinct
      properties in facilitating oligomerization of FGF2, as well as in binding to FGF
      receptors. In polySia-NCAM-expressing NIH-3T3 cells, which were established by
      transfecting cells with either of the plasmids for the expression of the
      polysialyltransferases ST8SiaII/STX and ST8SiaIV/PST that can polysialylate NCAM,
      FGF2-stimulated cell growth, but not cell survival, was inhibited. Taken
      together, these results suggest that polySia-NCAM might be involved in the
      regulation of FGF2-FGF receptor signaling through the direct binding of FGF2 in a
      manner distinct from heparan sulfate.

PMID- 22158872
TI  - Chemokine receptor 7 (CCR7) gene expression is regulated by NF-kappaB and
      activator protein 1 (AP1) in metastatic squamous cell carcinoma of head and neck
      (SCCHN).
AB  - The chemokine receptor CCR7 is a seven-transmembrane domain G-protein-coupled
      receptor that facilitates leukocyte migration to regional lymph nodes. Aberrant
      CCR7 expression in a number of human malignancies has been linked to pro
      survival, -invasive, and -metastatic pathways. We demonstrate here that up
      regulation of CCR7 in squamous cell carcinoma of the head and neck (SCCHN)
      patient tumors correlates with lower survival because of metastatic disease.
      Because of this important oncogenic phenotype, we investigated the mechanisms
      that regulate CCR7 expression in these tumors. Interestingly, the inflammatory
      transcription factor NF-kappaB has been associated with a more aggressive SCCHN
      phenotype. Immunohistochemical staining of a SCCHN tumor cohort (n = 47) strongly
      linked NF-kappaB staining and CCR7 expression in SCCHN. Thus, we investigated
      whether NF-kappaB contributes to metastatic disease by promoting CCR7 expression
      in SCCHN tumor cells. We characterized four novel, potential NF-kappaB binding
      sites in the 1000-bp promoter region upstream of the CCR7 gene, using luciferase,
      ChIP, and EMSA. However, NF-kappaB inhibition only resulted in partial reduction
      in CCR7 expression, prompting consideration of other co-regulators of CCR7.
      Indeed, cooperation between NF-kappaB and AP1 transcription factors, which are
      often co-activated, is crucial to the regulation of CCR7 mRNA expression in
      metastatic SCCHN cells. Thus, our findings support an important biological role
      for inflammatory NF-kappaB and AP1 in the regulation of CCR7 expression in
      metastatic SCCHN. As such, CCR7, NF-kappaB, and AP1 could be potentially useful
      therapeutic targets in controlling the progression and metastasis of SCCHN
      tumors.

PMID- 22158873
TI  - Interleukin (IL)-23 suppresses IL-10 in inflammatory bowel disease.
AB  - Interleukin (IL)-10 plays an important role in immune regulation in the
      intestine. Immune deregulation is suggested in the pathogenesis of inflammatory
      bowel disease (IBD). This study aims to elucidate the role of IL-23 in the
      suppression of IL-10 in the IBD intestinal mucosa. Surgically removed colon
      specimens were obtained from 16 IBD patients. The expressions of IL-10, IL-23,
      and IgA in the specimens were examined at the protein and gene transcriptional
      levels. The gene transcription of IL-10 was assessed by chromatin
      immunoprecipitation assay and promoter accessibility assay. The levels of IgA and
      IL-10 were significantly lower, whereas the levels of IL-23 were higher, in IBD
      specimens than in normal controls. The levels of IgA and IL-10 were negatively
      correlated with the infiltration of inflammatory cells in the IBD mucosa. The
      production of IL-10 by lamina propria mononuclear cells was lower in the IBD
      group than in the control group, and these levels could be enhanced by blocking
      IL-23. The gene transcription of IL-10 was significantly suppressed in CD4(+) T
      cells of IBD mucosa; this phenomenon could be replicated in vitro by adding IL-23
      in the culture of polarized Th2 cells. Overexpression of IL-23 in the intestinal
      mucosa suppresses the production of IL-10, which weakens the defensive barrier by
      reducing the production of IgA in the gut.

PMID- 22158874
TI  - Defining function of lipopolysaccharide O-antigen ligase WaaL using
      chemoenzymatically synthesized substrates.
AB  - The WaaL-mediated ligation of O-antigen onto the core region of the lipid A-core
      block is an important step in the lipopolysaccharide (LPS) biosynthetic pathway.
      Although the LPS biosynthesis has been largely characterized, only a limited
      amount of in vitro biochemical evidence has been established for the ligation
      reaction. Such limitations have primarily resulted from the barriers in purifying
      WaaL homologues and obtaining chemically defined substrates. Accordingly, we
      describe herein a chemical biology approach that enabled the reconstitution of
      this ligation reaction. The O-antigen repeating unit (O-unit) of Escherichia coli
      O86 was first enzymatically assembled via sequential enzymatic glycosylation of a
      chemically synthesized GalNAc-pyrophosphate-undecaprenyl precursor. Subsequent
      expression of WaaL through use of a chaperone co-expression system then enabled
      the demonstration of the in vitro ligation between the synthesized donor (O-unit
      pyrophosphate-undecaprenyl) and the isolated lipid A-core acceptor. The
      previously reported ATP and divalent metal cation dependence were not observed
      using this system. Further analyses of other donor substrates revealed that WaaL
      possesses a highly relaxed specificity toward both the lipid moiety and the
      glycan moiety of the donor. Lastly, three conserved amino acid residues
      identified by sequence alignment were found essential for the WaaL activity.
      Taken together, the present work represents an in vitro systematic investigation
      of the WaaL function using a chemical biology approach, providing a system that
      could facilitate the elucidation of the mechanism of WaaL-catalyzed ligation
      reaction.

PMID- 22158876
TI  - Foot-and-mouth disease virus epitope dominance in the antibody response of
      vaccinated animals.
AB  - Five neutralizing antigenic sites have been identified on the surface of serotype
      O foot-and-mouth disease virus (FMDV). A set of mAb neutralization-escape mutant
      viruses was used for the first time to evaluate the relative use of known binding
      sites by polyclonal antibodies from three target species: cattle, sheep and pigs.
      Antibodies to all five neutralizing antigenic sites were detected in all three
      species, with most antibodies directed against antigenic site 2, followed by
      antigenic site 1. In 76 % of cattle, 65 % of sheep and 58 % of pigs, most
      antibodies were directed against site 2. Antibodies specific to antigenic sites
      3, 4 and 5 were found to be minor constituents in the sera of each of the target
      species. This implies that antigenic site 2 is a dominant neutralization
      immunogenic site in serotype O FMDV and may therefore be a good candidate for
      designing novel vaccines.

PMID- 22158875
TI  - Interleukin-19 (IL-19) induces heme oxygenase-1 (HO-1) expression and decreases
      reactive oxygen species in human vascular smooth muscle cells.
AB  - Heme oxygenase-1 (HO-1) has potent anti-inflammatory activity and recognized
      vascular protective effects. We have recently described the expression and
      vascular protective effects of an anti-inflammatory interleukin (IL-19), in
      vascular smooth muscle cells (VSMC) and injured arteries. The objective of this
      study was to link the anti-inflammatory effects of IL-19 with HO-1 expression in
      resident vascular cells. IL-19 induced HO-1 mRNA and protein in cultured human
      VSMC, as assayed by quantitative RT-PCR, immunoblot, and ELISA. IL-19 does not
      induce HO-1 mRNA or protein in human endothelial cells. IL-19 activates STAT3 in
      VSMC, and IL-19-induced HO-1 expression is significantly reduced by transfection
      of VSMC with STAT3 siRNA or mutation of the consensus STAT binding site in the HO
      1 promoter. IL-19 treatment can significantly reduce ROS-induced apoptosis, as
      assayed by Annexin V flow cytometry. IL-19 significantly reduced ROS
      concentrations in cultured VSMC. The IL-19-induced reduction in ROS concentration
      is attenuated when HO-1 is reduced by siRNA, indicating that the IL-19-driven
      decrease in ROS is mediated by HO-1 expression. IL-19 reduces vascular ROS in
      vivo in mice treated with TNFalpha. This points to IL-19 as a potential
      therapeutic for vascular inflammatory diseases and a link for two previously
      unassociated protective processes: Th2 cytokine-induced anti-inflammation and ROS
      reduction.

PMID- 22158877
TI  - Interferon treatment suppresses enteric adenovirus infection in a model
      gastrointestinal cell-culture system.
AB  - Exposure to interferon results in the rapid transcriptional induction of genes,
      many of which function to create an antiviral environment in potential host
      cells. For the majority of adenoviruses, replication is unaffected by the actions
      of interferon. It has previously been shown, using non-gastrointestinal cells,
      that the species F human adenoviruses are sensitive to the action of interferon.
      Here, we have developed an enterocyte-like cell-culture model to re-evaluate this
      question, and determined the effects of interferon on species F adenovirus during
      infection of gastrointestinal cells. We show that species F adenovirus type 40 is
      sensitive to the effects of interferon in gastrointestinal-like cells, which may
      help to explain its fastidious growth in culture.

PMID- 22158878
TI  - Individuals infected with JC polyomavirus do not present detectable JC virus DNA
      in oropharyngeal fluids.
AB  - JC virus (JCV) is ubiquitous in the human population. Primary infection normally
      occurs during childhood and is followed by a lifelong persistent infection. The
      main mode of transmission remains unknown. Several authors have hypothesized that
      JCV transmission occurs through the respiratory route, and that respiratory
      secretions could represent a possible source of viral particles. The present
      study intended to evaluate oropharyngeal fluids from patients infected with JCV,
      in order to ascertain if respiratory secretions could indeed constitute a source
      of exposure to this polyomavirus. Oropharyngeal washing samples from 25 patients
      co-infected with JCV and human immunodeficiency virus type 1 were evaluated for
      the presence of JCV DNA. Regardless of the titre of antibodies or the presence of
      viral urinary excretion, JCV genome was not detected in oropharyngeal samples
      collected from any of the patients infected with JCV included in this study,
      which may suggest that oropharyngeal fluids are an unlikely source for JCV
      infection.

PMID- 22158879
TI  - The chromatin-tethering domain of human cytomegalovirus immediate-early (IE) 1
      mediates associations of IE1, PML and STAT2 with mitotic chromosomes, but is not
      essential for viral replication.
AB  - Human cytomegalovirus (HCMV) immediate-early (IE) 1 protein associates with
      chromosomes in mitotic cells using its carboxyl-terminal 16 aa region. However,
      the role of this IE1 activity in viral growth has not been evaluated in the
      context of mutant virus infection. We produced a recombinant HCMV encoding mutant
      IE1 with the carboxyl-terminal chromosome-tethering domain (CTD) deleted. This
      IE1(DeltaCTD) virus grew like the wild-type virus in fibroblasts, indicating that
      the CTD is not essential for viral replication in permissive cells. Unlike wild
      type virus infections, PML and STAT2, which interact with IE1, did not accumulate
      at mitotic chromosomes in IE1(DeltaCTD) virus-infected fibroblasts, demonstrating
      that their associations with chromosomes are IE1 CTD-dependent. IE1 SUMOylation
      did not affect IE1 association with chromosomes. Our results provide genetic
      evidence that the CTD is required for the associations of IE1, PML and STAT2 with
      mitotic chromosomes, but that these IE1-related activities are not essential for
      viral replication in fibroblasts.

PMID- 22158880
TI  - Multiple genomic sequences of hepatitis delta virus are associated with cDNA
      promoter activity and RNA double rolling-circle replication.
AB  - To understand how DNA-dependent RNA polymerase II (pol II) recognizes hepatitis
      delta virus (HDV) RNA as a template, it is first necessary to identify the HDV
      sequence that acts as a promoter of pol II-initiated RNA synthesis. Therefore, we
      isolated the pol II-response element from HDV cDNA and examined the regulation by
      hepatitis delta antigens (HDAgs). Two HDV cDNA fragments containing bidirectional
      promoter activity were identified. One was located at nt 1582-1683 (transcription
      promoter region 1, TR-P1) and the other at nt 1223-1363 (transcription-internal
      region 5, TR-I5). The promoter activities of these two regions were enhanced by
      HDAgs to differing degrees. Next, the role of these sequences in an HDV cDNA-free
      RNA replication system was characterized by site-directed mutagenesis. Our data
      showed that: (i) the AUG codon at the HDAg ORF of HDV RNA (nt 1599-1601) that
      mutates to UAG (amber stop codon) results in loss of dimeric but not monomeric
      HDV RNA synthesis. (ii) A 5 nt mutation of TR-P1 (P1-m5, nt 1670-1674) abolishes
      RNA replication completely. Two-nucleotide-mutated RNA (P1-m2, nt 1662-1663) is
      able to synthesize short RNAs but not monomeric HDV RNA. (iii) A mutation in 5 nt
      at the TR-I5 region (I5-m5, nt 1351-1355) also abolishes HDV replication. Mutants
      with 2 nt mutations (I5-m2, nt 1351-1352) or 3 nt mutations (I5-m3, nt 1353-1355)
      inhibit HDV dimeric but not monomeric RNA synthesis. Furthermore, large HDAg is
      expressed in cells transfected with I5-m3 and I5-m2 RNAs and that demonstrate the
      RNA-editing event in the monomeric HDV RNA. These results provide further
      understanding of the double rolling-circle mechanism in HDV RNA replication.

PMID- 22158881
TI  - Biochemical analysis of infected cell polypeptide (ICP)0, ICP4, UL7 and UL23
      incorporated into extracellular herpes simplex virus type 1 virions.
AB  - Herpes simplex virus type 1 (HSV-1) capsids assemble in the nucleus but acquire
      their teguments from various cellular compartments. Unfortunately, little is
      known about their exact arrangement and when they coat the newly produced
      capsids. The complexity of the virions is further highlighted by our recent
      proteomics analysis that detected the presence of several novel or controversial
      components in extracellular HSV-1 virions. The present study probes the
      localization and linkage to the virus particles of some of these incorporated
      proteins. We confirm the recently reported tight association of infected cell
      polypeptide (ICP)0 with the capsid and show that this property extends to ICP4.
      We also confirm our proteomics data and show biochemically that UL7 and UL23 are
      indeed mature virion tegument components that, unlike ICP0 and ICP4, are salt
      extractable. Interestingly, treatment with N-ethylmaleimide, which covalently
      modifies reduced cysteines, strongly prevented the release of UL7 and UL23 by
      salts, but did not perturb the interactions of ICP0 and ICP4 with the virus
      particles. This hitheir at distinct biochemical properties of the virion
      constituents and the selective implication of reduced cysteines in their
      organization and dynamics. Finally, the data revealed, by two independent means,
      the presence of ICP0 and ICP4 on intranuclear capsids, consistent with the
      possibility that they may at least partially be recruited to the virus particles
      early on. These findings add significantly to our understanding of HSV-1 virion
      assembly and to the debate about the incorporation of ICP0 and ICP4 in virus
      particles.

PMID- 22158882
TI  - The HBx protein of hepatitis B virus regulates the expression, intracellular
      distribution and functions of ribosomal protein S27a.
AB  - The pleiotropic HBx protein of hepatitis B virus is linked functionally to the
      development of hepatocellular carcinoma (HCC) via effectors and signalling
      pathways of the host. To identify such effectors in a macrocarcinogenic
      environment, a PCR-based cDNA subtraction analysis was carried out in the X15-myc
      oncomouse model of HCC. Altogether, 19 categories of genes, mainly involved in
      protein biosynthesis and the electron-transport chain, were found to be
      upregulated in the liver of these mice. Ribosomal protein S27a (RPS27a), which is
      a natural fusion protein of N-terminal ubiquitin and C-terminal extension protein
      (CEP), topped the list of expressed genes, with >20-fold higher expression
      compared with its normal level. Sustained and elevated expression of RPS27a in
      the mouse liver and its moderate expression in cell culture in the presence of
      HBx suggested an indirect role of RPS27a in hepatocarcinogenesis. Nevertheless, a
      remarkable change in the intracellular distribution of ubiquitin from cytoplasm
      to late-endosomal lysosomes, and of CEP from nucleoli to the perinucleolar
      region/nuclear foci, was observed in the presence of HBx. RPS27a accelerated the
      progression of the cell cycle and cooperated with HBx in this process. Further,
      the knockdown of RPS27a expression by RNA interference in an HBx microenvironment
      led to retarded cell-cycle progression and reduced cell size. Thus, these results
      suggest strongly that RPS27a could be an effector of HBx-mediated
      hepatocarcinogenesis.

PMID- 22158883
TI  - Magnetic nanosensors for highly sensitive and selective detection of bacillus
      Calmette-Guerin.
AB  - With current concerns of the global threat from tuberculosis, it has become
      important to rapidly identify the bacteria. Traditional technologies involving
      isolation and amplification of the pathogenic bacteria are complicated and time
      consuming. In this work, we describe a sensitive NMR-based detection method to
      identify bacteria via bacteria-induced self-assembly of magnetic nanoparticles.
      Bacillus Calmette-Guerin (BCG) was used as a surrogate for Mycobacterium
      tuberculosis. We prepared the probes by covalent immobilization of the anti-BCG
      monoclonal antibody onto carboxylic acid-functionalized magnetic nanoparticles.
      Once a solution containing BCG was introduced, the probes switched from a well
      dispersed state to an aggregated one, leading to a distinct and dose-dependent
      change in the spin-spin relaxation time (T2) of the solution. Thus the
      qualitative and quantitative detection method for BCG was established. The method
      provides specific detection of as few as 8 bacterial cells per millilitre in
      experimental samples within 1 hour, which will be promising for rapid detection
      of M. tuberculosis in clinical samples.

PMID- 22158884
TI  - Socio-demographic and work-related risk factors for medium- and long-term
      sickness absence among Italian workers.
AB  - BACKGROUND: Few studies investigated determinants of sickness absence in
      representative samples of the general population, none of which in Italy. Aim of
      this study was to assess influence and relative importance of socio-demographic
      and work-related characteristics on medium- and long-term sickness absence in a
      random sample of Italian workers. METHODS: Approximately 60,000 workers
      participating in a national survey in 2007 were interviewed regarding sickness
      absence during the whole previous week, and on socio-demographics, employment
      characteristics and exposure to a set of physical and psychosocial hazards in the
      workplace. The association between sickness absence and potential determinants
      was estimated by multivariable logistic regression models stratified by gender.
      RESULTS: From the final multivariate models, in both genders sickness absence was
      statistically significantly associated with tenure employment, working in larger
      firms, exposure to risk of injury and to bullying or discrimination and, among
      employees, with shift work. In males, sickness absence was also associated with
      lower education, employment in the public administration and with exposure to
      noise or vibration, whereas among women also with manual work and ergonomic
      factors. In both genders, the attributable fraction for employment-related
      characteristics was higher than that for socio-demographic ones. CONCLUSIONS: The
      association with tenure or salaried jobs, and with employment in larger firms or
      in the public sector suggests that, besides illness, job security is the most
      important determinant of sickness absence, consistently with the results of
      previous studies. However, our results indicate that a reduction in exposure to
      workplace hazards may contribute to reduce absenteeism.

PMID- 22158885
TI  - Central adrenergic receptors.

PMID- 22158886
TI  - Melancholia.

PMID- 22158887
TI  - Midazolam cue in rats: effects of drugs acting on GABA and 5-hydroxytryptamine
      systems, anticonvulsants and sedatives.
AB  - The discriminative stimulus effect of midazolam, a short-acting benzodiazepine,
      was used for testing the effects of related drugs including agents thought to act
      at different sites in the proposed benzodiazepine receptor complex. Rats were
      trained in a standard two- bar operant conditioning procedure with food
      reinforcers delivered on a tandem schedule. The 0.4 mg/kg dose of midazolam used
      for training was well discriminated, typically yielding about 95% correct
      responding. There was no generalization to the GABA agonists muscimol and THIP,
      to the 5-HT antagonists cyproheptadine and methergoline, to buspirone, CGS 9896,
      ethanol, Ro 5-4864, promethazine, phenytoin sodium or sodium valproate. Muscimol
      and THIP also failed to potentiate the effects of midazolam. The GABA antagonist
      bicuculline weakly attenuated the discriminative effect of midazolam without
      impairing generalization to pentobarbitone, whereas the benzodiazepine inverse
      agonist FG 7142 did not attenuate the effect of midazolam. The results provide
      additional evidence for the notable specificity of the midazolam cue but do
      little to link the behavioural effects of benzodiazepines to GABA or 5- HT
      systems. Perhaps the potency, efficacy or selectivity of the GABA agonists was
      inadequate to produce the expected results. Only the effects of bicuculline, and
      those reported previously for picrotoxin, provided some support for the
      hypothesis that midazolam cue is mediated by the GABA system.

PMID- 22158888
TI  - The effects of single doses of alpidem and lorazepam on memory and psychomotor
      performance in normal humans.
AB  - Two studies are reported which compare different single doses of alpidem
      (SL80.0343-00) with lorazepam 2 mg. In the first study, lorazepam and the highest
      (100 mg) dose of alpidem impaired performance on a range of psychomotor tasks,
      although the effects of lorazepam were more severe and persisted for longer than
      those of alpidem. In comparison, alpidem 50 and 25 mg had little effect. The EEG
      profiles of both drugs were similar.

PMID- 22158889
TI  - The effect of metergoline on endocrine responses to L-tryptophan.
AB  - The effects of the 5-HT receptor antagonist, metergoline, on the prolactin and
      growth hormone responses to intravenous L-tryptophan were assessed in seven
      normal subjects. Pretreatment with metergoline lowered baseline prolactin
      concentration and abol ished the increase in prolactin following L-tryptophan. In
      contrast, neither baseline nor the response to L-tryptophan was altered by
      metergoline. These results are consistent with the proposal that the prolactin
      response to L-tryptophan is mediated by 5-HT(1) receptors; however, metergoline
      might also reduce prolactin responses by a dopaminergic action. The nature of the
      5-HT receptor involved in the growth hormone response to L-tryptophan remains to
      be identified.

PMID- 22158890
TI  - A brief review of studies of piracetam in dyslexia.
AB  - Several double-blind studies of the effects of piracetam in developmental
      dyslexia are reviewed. There is general agreement among studies that piracetam
      appears to improve reading performance.

PMID- 22158891
TI  - Alterations in dopamine and 5-hydroxytryptamine (5-HT) function during
      barbiturate dependence and withdrawal in mice.
AB  - Mice were rendered barbiturate-dependent by chronic feeding with barbital-con
      taining food. Brain dopamine turnover was significantly increased in barbital
      withdrawal, whereas 5-hydroxytryptamine (5-HT) turnover was significantly
      decreased. Severity of with drawal was assessed by measuring the convulsions
      following a dose of 33 mg/kg mer captopropionate (MPA). The neurotoxins 6
      hydroxydopamine and 5,6-dihydroxytryptamine as well as metergoline (5 mg/kg)
      increased the severity of MPA convulsions. Quipazine (20 mg/ kg) attenuated the
      convulsions. The results are consistent with the hypothesis that diminished 5-HT
      function may contribute to the barbital withdrawal syndrome. Behavioural
      responses to serotonergic drugs were enhanced in barbital-dependent mice compared
      to controls, but [(3)H]- 5-HT binding to crude membrane fractions was similar in
      both groups with a single high affinity site.

PMID- 22158892
TI  - The psychopharmacology of the human pineal.
AB  - In many ways the pineal is an ideal endocrine gland for the biological
      psychiatrist. The gland is small, circumscribed and relatively homogeneous, so it
      can be studied either in tissue culture or in vivo. The results from such studies
      combine to give a well-characterized model for investigating noradrenergic
      neurotransmission. In the pineal as in the brain there is a noradrenaline uptake
      site, an autoreceptor which regulates noradrenaline release, and there are post
      junctional beta(1) and alpha(1)-adrenoceptors. In the pineal as in the brain the
      beta(1) adrenoceptor is linked to adenylate cyclase and the alpha( 1)
      adrenoceptor is coupled with phos phatidyl inositol (PI) turnover: both second
      messenger systems combine to influence mela tonin secretion.

PMID- 22158893
TI  - Lorazepam in the elderly--a retrospective study of the side-effects in 20
      patients.
AB  - In a retrospective study of 20 elderly patients who were prescribed lorazepam
      prior to their admission to a geriatric psychiatry inpatient unit, the average
      length of prescription of the drug was 18 weeks with inadequate follow-up. Side
      effects were common and consisted of oversedation, amnestic disorders, confusion,
      depression and ataxia. The majority of such events resolved on withdrawal of
      lorazepam in hospital. Particular note is made of the pro duction of a drug
      induced pseudodementia misdiagnosed as a 'true' dementia which again resolved on
      cessation of the drug. It is concluded that there are insufficient data to
      recommend lorazepam over any other agent in the elderly and care should always be
      exercised when prescribing in older patients.

PMID- 22158894
TI  - Near-infrared dual luminescence from an extended zinc porphyrin.
AB  - The photophysical characterization of an extended zinc porphyrin is reported.
      Fusion of bis-tetraazaanthracene on the porphyrin ring causes an unusual dual
      luminescence ascribed to two non-equilibrated singlet excited states.

PMID- 22158895
TI  - Remodeling of actin filaments by ADF/cofilin proteins.
AB  - Cofilin/ADF proteins play key roles in the dynamics of actin, one of the most
      abundant and highly conserved eukaryotic proteins. We used cryoelectron
      microscopy to generate a 9-A resolution three-dimensional reconstruction of
      cofilin-decorated actin filaments, the highest resolution achieved for a complex
      of F-actin with an actin-binding protein. We show that the cofilin-induced change
      in the filament twist is due to a unique conformation of the actin molecule
      unrelated to any previously observed state. The changes between the actin
      protomer in naked F-actin and in the actin-cofilin filament are greater than the
      conformational changes between G- and F-actin. Our results show the structural
      plasticity of actin, suggest that other actin-binding proteins may also induce
      large but different conformational changes, and show that F-actin cannot be
      described by a single molecular model.

PMID- 22158896
TI  - Covalent modification of reduced flavin mononucleotide in type-2 isopentenyl
      diphosphate isomerase by active-site-directed inhibitors.
AB  - Evidence for an unusual catalysis of protonation/deprotonation by a reduced
      flavin mononucleotide cofactor is presented for type-2 isopentenyl diphosphate
      isomerase (IDI-2), which catalyzes isomerization of the two fundamental building
      blocks of isoprenoid biosynthesis, isopentenyl diphosphate and dimethylallyl
      diphosphate. The covalent adducts formed between irreversible mechanism-based
      inhibitors, 3-methylene-4-penten-1-yl diphosphate or 3-oxiranyl-3-buten-1-yl
      diphosphate, and the flavin cofactor were investigated by X-ray crystallography
      and UV-visible spectroscopy. Both the crystal structures of IDI-2 binding the
      flavin-inhibitor adduct and the UV-visible spectra of the adducts indicate that
      the covalent bond is formed at C4a of flavin rather than at N5, which had been
      proposed previously. In addition, the high-resolution crystal structures of IDI-2
      substrate complexes and the kinetic studies of new mutants confirmed that only
      the flavin cofactor can catalyze protonation of the substrates and suggest that
      N5 of flavin is most likely to be involved in proton transfer. These data provide
      support for a mechanism where the reduced flavin cofactor acts as a general
      acid/base catalyst and helps stabilize the carbocationic intermediate formed by
      protonation.

PMID- 22158897
TI  - Rational design of an evolutionary precursor of glutaminyl-tRNA synthetase.
AB  - The specificity of most aminoacyl-tRNA synthetases for an amino acid and cognate
      tRNA pair evolved before the divergence of the three domains of life. Glutaminyl
      tRNA synthetase (GlnRS) evolved later and is derived from the archaeal-type
      nondiscriminating glutamyl-tRNA synthetase (GluRS), an enzyme with relaxed tRNA
      specificity capable of forming both Glu-tRNA(Glu) and Glu-tRNA(Gln). The archaea
      lack GlnRS and use a specialized amidotransferase to convert Glu-tRNA(Gln) to Gln
      tRNA(Gln) needed for protein synthesis. We show that the Methanothermobacter
      thermautotrophicus GluRS is active toward tRNA(Glu) and the two tRNA(Gln)
      isoacceptors the organism encodes, but with a significant catalytic preference
      for tRNA(Gln2)(CUG). The less active tRNA(Gln1)(UUG) responds to the less common
      CAA codon for Gln. From a biochemical characterization of M. thermautotrophicus
      GluRS variants, we found that the evolution of tRNA specificity in GlnRS could be
      recapitulated by converting the M. thermautotrophicus GluRS to a tRNA(Gln)
      specific enzyme, solely through the addition of an acceptor stem loop present in
      bacterial GlnRS. One designed GluRS variant is also highly specific for the
      tRNA(Gln2)(CUG) isoacceptor, which responds to the CAG codon, and shows no
      activity toward tRNA(Gln1)(UUG). Because it is now possible to eliminate
      particular codons from the genome of Escherichia coli, additional codons will
      become available for genetic code engineering. Isoacceptor-specific aminoacyl
      tRNA synthetases will enable the reassignment of more open codons while
      preserving accurate encoding of the 20 canonical amino acids.

PMID- 22158898
TI  - Coupling mammalian cell surface display with somatic hypermutation for the
      discovery and maturation of human antibodies.
AB  - A novel approach has been developed for the isolation and maturation of human
      antibodies that replicates key features of the adaptive immune system by coupling
      in vitro somatic hypermutation (SHM) with mammalian cell display. SHM is
      dependent on the action of the B cell specific enzyme, activation-induced
      cytidine deaminase (AID), and can be replicated in non-B cells through expression
      of recombinant AID. A library of human antibodies, based on germline V-gene
      segments with recombined human   regions was used to isolate low-affinity
      antibodies to human beta nerve growth factor (hbetaNGF). These antibodies,
      initially naive to SHM, were subjected to AID-directed SHM in vitro and selected
      using the same mammalian cell display system, as illustrated by the maturation of
      one of the antibodies to low pM K(D). This approach overcomes many of the
      previous limitations of mammalian cell display, enabling direct selection and
      maturation of antibodies as full-length, glycosylated IgGs.

PMID- 22158899
TI  - Crystal structure of the mucosa-associated lymphoid tissue lymphoma translocation
      1 (MALT1) paracaspase region.
AB  - The mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1)
      paracaspase, a key component of the Carma1/Bcl10/MALT1 signalosome, is critical
      for NF-kappaB signaling in multiple contexts. MALT1 is thought to function as a
      scaffold and protease to promote signaling; however, the biochemical and
      structural basis of paracaspase action remains largely unknown. Here we report
      the 1.75-A resolution crystal structure of the MALT1 paracaspase region, which
      contains the paracaspase domain and an ensuing Ig-like domain. The paracaspase
      and the Ig domains appear as a single folding unit and interact with each other
      through extensive van der Waals contacts and hydrogen bonds. The paracaspase
      domain adopts a fold that is nearly identical to that of classic caspases and
      homodimerizes similarly to form an active protease. Unlike caspases, the active
      and mature form of the paracaspase domain remains a single uncleaved polypeptide
      and specifically recognizes the bound peptide inhibitor Val-Arg-Pro-Arg. In
      particular, the carboxyl-terminal amino acid Arg of the inhibitor is coordinated
      by three highly conserved acidic residues. This structure serves as an important
      framework for deciphering the function and mechanism of paracaspases exemplified
      by MALT1.

PMID- 22158900
TI  - Structural analysis of the core COMPASS family of histone H3K4 methylases from
      yeast to human.
AB  - Histone H3 lysine 4 (H3K4) methylation is catalyzed by the highly evolutionarily
      conserved multiprotein complex known as Set1/COMPASS or MLL/COMPASS-like
      complexes from yeast to human, respectively. Here we have reconstituted fully
      functional yeast Set1/COMPASS and human MLL/COMPASS-like complex in vitro and
      have identified the minimum subunit composition required for histone H3K4
      methylation. These subunits include the methyltransferase C-terminal SET domain
      of Set1/MLL, Cps60/Ash2L, Cps50/RbBP5, Cps30/WDR5, and Cps25/Dpy30, which are all
      common components of the COMPASS family from yeast to human. Three-dimensional
      (3D) cryo-EM reconstructions of the core yeast complex, combined with
      immunolabeling and two-dimensional (2D) EM analysis of the individual
      subcomplexes reveal a Y-shaped architecture with Cps50 and Cps30 localizing on
      the top two adjacent lobes and Cps60-Cps25 forming the base at the bottom. EM
      analysis of the human complex reveals a striking similarity to its yeast
      counterpart, suggesting a common subunit organization. The SET domain of Set1 is
      located at the juncture of Cps50, Cps30, and the Cps60-Cps25 module, lining the
      walls of a central channel that may act as the platform for catalysis and
      regulative processing of various degrees of H3K4 methylation. This structural
      arrangement suggested that COMPASS family members function as exo-methylases,
      which we have confirmed by in vitro and in vivo studies.

PMID- 22158901
TI  - 3D structure of the Yersinia entomophaga toxin complex and implications for
      insecticidal activity.
AB  - Toxin complex (Tc) proteins are a class of bacterial protein toxins that form
      large, multisubunit complexes. Comprising TcA, B, and C components, they are of
      great interest because many exhibit potent insecticidal activity. Here we report
      the structure of a novel Tc, Yen-Tc, isolated from the bacterium Yersinia
      entomophaga MH96, which differs from the majority of bacterially derived Tcs in
      that it exhibits oral activity toward a broad range of insect pests, including
      the diamondback moth (Plutella xylostella). We have determined the structure of
      the Yen-Tc using single particle electron microscopy and studied its mechanism of
      toxicity by comparative analyses of two variants of the complex exhibiting
      different toxicity profiles. We show that the A subunits form the basis of a
      fivefold symmetric assembly that differs substantially in structure and subunit
      arrangement from its most well characterized homologue, the Xenorhabdus
      nematophila toxin XptA1. Histopathological and quantitative dose response
      analyses identify the B and C subunits, which map to a single, surface-accessible
      region of the structure, as the sole determinants of toxicity. Finally, we show
      that the assembled Yen-Tc has endochitinase activity and attribute this to
      putative chitinase subunits that decorate the surface of the TcA scaffold, an
      observation that may explain the oral toxicity associated with the complex.

PMID- 22158902
TI  - Autoinhibition and phosphorylation-induced activation mechanisms of human cancer
      and autoimmune disease-related E3 protein Cbl-b.
AB  - Cbl-b is a RING-type E3 ubiquitin ligase that functions as a negative regulator
      of T-cell activation and growth factor receptor and nonreceptor-type tyrosine
      kinase signaling. Cbl-b dysfunction is related to autoimmune diseases and cancers
      in humans. However, the molecular mechanism regulating its E3 activity is largely
      unknown. NMR and small-angle X-ray scattering analyses revealed that the
      unphosphorylated N-terminal region of Cbl-b forms a compact structure by an
      intramolecular interaction, which masks the interaction surface of the RING
      domain with an E2 ubiquitin-conjugating enzyme. Phosphorylation of Y363, located
      in the helix-linker region between the tyrosine kinase binding and the RING
      domains, disrupts the interdomain interaction to expose the E2 binding surface of
      the RING domain. Structural analysis revealed that the phosphorylated helix-RING
      region forms a compact structure in solution. Moreover, the phosphate group of
      pY363 is located in the vicinity of the interaction surface with UbcH5B to
      increase affinity by reducing their electrostatic repulsion. Thus, the
      phosphorylation of Y363 regulates the E3 activity of Cbl-b by two mechanisms: one
      is to remove the masking of the RING domain from the tyrosine kinase binding
      domain and the other is to form a surface to enhance binding affinity to E2.

PMID- 22158904
TI  - Anaerobic work capacity's contribution to 5-km-race performance in female
      runners.
AB  - PURPOSE: The purpose of this study was to examine the relationship between
      anaerobic characteristics and 5-km-race performance in trained female cross
      country runners (N = 13). METHODS: The runners performed 50-m sprints and a 5-km
      time trial on an outdoor 400-m track and maximal anaerobic (MART) and aerobic
      running tests on a motorized treadmill. Anaerobic characteristics were determined
      by the mean velocity of the 50-m sprint (v50m) and the peak velocity in the MART
      (vMART). The aerobic characteristics were obtained during the aerobic treadmill
      test and included maximal oxygen uptake (VO2max), running economy, and
      ventilatory threshold (VT). RESULTS: Both the vMART (r = .69, P < .01) and VO2max
      (r = .80, P < .01) correlated with the mean velocity of the 5-km (v5km). A
      multiple-linear-regression analysis revealed that the combination of VO2max,
      vMART, and VT explained 81% (R2 = .81, P < .001) of the variation seen in the
      v5km. The vMART accounted for 31% of the total shared variance, while the
      combination of VO2max and VT explained the remaining 50%. CONCLUSIONS: These
      results suggest that among trained female runners who are relatively matched,
      anaerobic energy production can effectively discriminate the v5km and explain a
      significant amount of the variation seen in 5-km-race performance.

PMID- 22158903
TI  - Legionella pneumophila regulates the small GTPase Rab1 activity by reversible
      phosphorylcholination.
AB  - Effectors delivered into host cells by the Legionella pneumophila Dot/Icm type IV
      transporter are essential for the biogenesis of the specialized vacuole that
      permits its intracellular growth. The biochemical function of most of these
      effectors is unknown, making it difficult to assign their roles in the
      establishment of successful infection. We found that several yeast genes involved
      in membrane trafficking, including the small GTPase Ypt1, strongly suppress the
      cytotoxicity of Lpg0695(AnkX), a protein known to interfere severely with host
      vesicle trafficking when overexpressed. Mass spectrometry analysis of Rab1
      purified from a yeast strain inducibly expressing AnkX revealed that this small
      GTPase is modified posttranslationally at Ser(76) by a phosphorylcholine moiety.
      Using cytidine diphosphate-choline as the donor for phosphorylcholine, AnkX
      catalyzes the transfer of phosphorylcholine to Rab1 in a filamentation-induced by
      cAMP(Fic) domain-dependent manner. Further, we found that the activity of AnkX is
      regulated by the Dot/Icm substrate Lpg0696(Lem3), which functions as a
      dephosphorylcholinase to reverse AnkX-mediated modification on Rab1.
      Phosphorylcholination interfered with Rab1 activity by making it less accessible
      to the bacterial GTPase activation protein LepB; this interference can be
      alleviated fully by Lem3. Our results reveal reversible phosphorylcholination as
      a mechanism for balanced modulation of host cellular processes by a bacterial
      pathogen.

PMID- 22158905
TI  - Immunotherapy with PI3K inhibitor and Toll-like receptor agonist induces IFN
      gamma+IL-17+ polyfunctional T cells that mediate rejection of murine tumors.
AB  - The immunosuppressive microenvironment in tumors hampers the induction of
      antitumor immunity by vaccines or immunotherapies. Toll-like receptor (TLR)
      ligands have the potential to treat tumors, but they can exert a mixture of
      positive and negative effects on inflammation in the tumor microenvironment. In
      this study, we show that specific small molecule inhibitors of phosphoinositide 3
      kinase (PI3K) relieve immunosuppression to heighten the proinflammatory effects
      of TLR ligands that support antitumor immunity. Multiple strategies to inhibit
      PI3K in dendritic cells (DC) each led to suppression of interleukin (IL)-10 and
      TGF-beta but did affect IL-12 or IL-1beta induction by the TLR5 ligand flagellin.
      In three different mouse models of cancer, combining flagellin with a class I
      PI3K inhibitor, either with or without a DC vaccine, delayed tumor growth and
      increased survival, with some animals exhibiting complete rejection and
      resistance to secondary challenge. Tumor growth suppression was associated with
      increased accumulation of polyfunctional T cells that secreted multiple effector
      cytokines, including IFN-gamma, IL-17, and IL-2. Therapeutic protection was
      abolished in mice deficient in IL-17 or deprived of IFN-gamma. Together, our
      results indicate that PI3K inhibition heighten the antitumor properties of TLR
      ligands, eliciting tumor regression directly but also indirectly by relieving
      suppressive signals that restrict potent antitumor T-cell responses. These
      findings suggest important uses for PI3K inhibitors in heightening responses to
      cancer immunotherapy and immunochemotherapy.

PMID- 22158906
TI  - Up-regulation of miR-1245 by c-myc targets BRCA2 and impairs DNA repair.
AB  - BRCA2, a clinical prognostic factor, is significantly up-regulated in mRNA level,
      while its protein expression is often decreased in sporadic breast cancer.
      However, how BRCA2 protein expressions are suppressed in these tumors remains
      unknown. In this study, we demonstrated that miR-1245 directly suppressed BRCA2
      3'-UTR and translation, impaired homologous recombination (HR)-mediated repair,
      reduced DNA damage-induced Rad51 nuclear foci, and rendered cells hypersensitive
      to gamma-irradiation (IR), ultimately inducing high chromosomal abnormalities in
      normal breast cells and breast cancer cells. Conversely, inhibiting miR-1245 in
      breast cancer cells enhanced BRCA2 levels and induced resistance to IR.
      Furthermore, we demonstrated that c-myc up-regulated miR-1245 expression via
      direct binding to the miR-1245 promoter, which led to down-regulation of BRCA2
      and reduction in HR efficiency. Significantly, miR-1245 levels in primary breast
      tumors correlated with c-myc overexpression and BRCA2 suppression. These findings
      uncover a BRCA2 regulatory and signaling pathway in sporadic breast cancer and
      support a functionally and clinically relevant epigenetic mechanism in cancer
      pathogenesis.

PMID- 22158907
TI  - TGF-beta: the sword, the wand, and the shield of FOXP3(+) regulatory T cells.
AB  - Since its rediscovery in the mid-1990s, FOXP3(+) regulatory T cells (Tregs) have
      climbed the rank to become commander-in-chief of the immune system. They possess
      diverse power and ability to orchestrate the immune system in time of
      inflammation and infection as well as in time of harmony and homeostasis. To be
      the commander-in-chief, they must be equipped with both offensive and defensive
      weaponry. This review will focus on the function of transforming growth factor
      beta (TGF-beta) as the sword, the wand, and the shield of Tregs. Functioning as a
      sword, this review will begin with a discussion of the evidence that supports how
      Tregs utilize TGF-beta to paralyze cell activation and differentiation to
      suppress immune response. It will next provide evidence on how TGF-beta from
      Tregs acts as a wand to convert naive T cells into iTregs and Th17 to aid in
      their combat against inflammation and infection. Lastly, the review will present
      evidence on the role of TGF-beta produced by Tregs in providing a shield to
      protect and maintain Tregs against apoptosis and destabilization when surrounded
      by inflammation and constant stimulation. This triadic function of TGF-beta
      empowers Tregs with the responsibility and burden to maintain homeostasis,
      promote immune tolerance, and regulate host defense against foreign pathogens.

PMID- 22158908
TI  - Hydroxylated surface of GaAs as a scaffold for a heterogeneous Pd catalyst.
AB  - A novel use of GaAs, namely, as a scaffold for a heterogeneous palladium
      catalyst, is proposed. Hydroxy groups on the GaAs surface play important roles.
      During the adsorption of Pd(OAc)(2) on the GaAs surface, the hydroxy groups
      attract Pd(ii) species by anion exchange. A subsequent redox reaction proceeds to
      generate Pd(0) nanoparticles, which are stabilized on the GaAs surface. This
      process is confirmed by surface-sensitive measurements: diffuse reflection IR
      spectroscopy and X-ray photoelectron spectroscopy. Moreover, a more bulk
      sensitive measurement, hard X-ray photoemission spectroscopy with synchrotron
      radiation, also supported our considerations. The amounts of Pd(0) nanoparticles
      on the surface were evaluated by catalytic activity, yield, and recyclability in
      the Heck reaction, in addition to the deposit test.

PMID- 22158909
TI  - The role of empathy in anger arousal in violent offenders and university
      students.
AB  - A lack of empathic responsiveness toward others has been consistently identified
      as an important antecedent to aggressive behavior and violent crime, with many
      rehabilitation programs for violent offenders incorporating treatment modules
      that are specifically designed to increase offender empathy. This study examined
      the extent to which cognitive (perspective taking) and affective (empathic
      concern, personal distress) empathy predicted anger in a clinical (male prisoners
      convicted of a violent offense) and a nonclinical (student) sample. Perspective
      taking emerged as the strongest predictor of self-reported anger in response to
      an interpersonal provocation, as well as being most consistently related to
      scores on measures of general trait anger and methods of anger control. While the
      relationship between perspective taking and anger was apparent for offenders as
      well as students, the results did not support the idea that an inability to
      perspective take is a particular characteristic of violent offenders.

PMID- 22158910
TI  - Factors contributing to perceptions about policies regarding the electronic
      monitoring of sex offenders: the role of demographic characteristics,
      victimization experiences, and social disorganization.
AB  - The purpose of this article is to explore factors contributing to perceptions
      about electronic monitoring policies governing sex offenders. Guided by
      Tannenbaum's theory of attribution and Shaw and McKay's theory of social
      disorganization, the authors examine the influence of demographic
      characteristics, victimization experiences, and neighborhood characteristics on
      perceptions about policies regarding the electronic monitoring of sex offenders.
      Ordinary least squares regression and logistic regression analyses of stratified
      telephone survey data reveal that factors associated with favorable views on the
      use of global positioning satellite monitoring for registered sex offenders
      appear to stem primarily from individuals' demographic characteristics.
      Experiential and neighborhood factors do provide some influence over individuals'
      views of electronic monitoring policies for sex offenders. Theoretical and policy
      implications are discussed.

PMID- 22158911
TI  - Predicting juvenile offending: a comparison of data mining methods.
AB  - In this study, the authors compared logistic regression and predictive data
      mining techniques such as decision trees (DTs), artificial neural networks
      (ANNs), and support vector machines (SVMs), and examined these methods on whether
      they could discriminate between adolescents who were charged or not charged for
      initial juvenile offending in a large Asian sample. Results were validated and
      tested in independent samples with logistic regression and DT, ANN, and SVM
      classifiers achieving accuracy rates of 95% and above. Findings from receiver
      operating characteristic analyses also supported these results. In addition, the
      authors examined distinct patterns of occurrences within and across classifiers.
      Proactive aggression and teacher-rated conflict consistently emerged as risk
      factors across validation and testing data sets of DT and ANN classifiers, and
      logistic regression. Reactive aggression, narcissistic exploitativeness, being
      male, and coming from a nonintact family were risk factors that emerged in one or
      more of these data sets across classifiers, while anxiety and poor peer
      relationships failed to emerge as predictors.

PMID- 22158913
TI  - Public-private partnerships in public health research: does it work and if yes,
      how?

PMID- 22158912
TI  - Copper-free click--a promising tool for pre-targeted PET imaging.
AB  - The copper-free click (CFC) reaction has been evaluated for its potential
      application to in vivo pre-targeting for PET imaging. A promising biodistribution
      profile is demonstrated when employing [(18)F]2-fluoroethylazide ([(18)F]1) and
      optimisation of the CFC reaction with a series of cyclooctynes shows that
      reactions proceed efficiently with tantalizing opportunities for application
      specific tuning.

PMID- 22158914
TI  - Low serum lycopene and beta-carotene increase risk of acute myocardial infarction
      in men.
AB  - OBJECTIVE: Previous studies have shown that high intake or concentrations of
      serum carotenoids may protect against acute myocardial infarction (AMI). The role
      of carotenoids on the risk of AMI remains inconsistent. The aim of the present
      study was to examine if serum concentrations of major carotenoids are related to
      AMI in men. METHODS: The study population consisted of 1031 Finnish men aged 46
      65 years in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort. Serum
      concentrations of carotenoids, retinol and alpha-tocopherol were measured by high
      performance liquid chromatography. The association between the serum
      concentrations of lycopene alpha-carotene and beta-carotene and the risk of AMI
      was studied by using the Cox proportional hazard models. RESULTS: A total of 194
      incident AMI cases occurred during an average of 11.5 follow-up years. After
      adjusting for potential confounders, the risk of AMI for men in the lowest
      tertile of serum concentrations compared with men in the highest tertile was 1.55
      (95% CI 1.05- 2.30; P = 0.028) for lycopene and 1.60 (95% CI 1.09-2.35; P =
      0.017) for beta-carotene. CONCLUSIONS: This cross-sectional study shows that low
      serum lycopene and beta-carotene concentrations may increase the risk of AMI in
      men.

PMID- 22158915
TI  - Effect of pseudoephedrine on 800-m-run times of female collegiate track athletes.
AB  - CONTEXT: Pseudoephedrine (PSE) is an over-the-counter decongestant that might
      have ergogenic effects. The World Anti-Doping Agency has prohibited large doses
      (>150 MUg/mL) of PSE, while the National College Athletic Association (NCAA) does
      not include it on their banned-substance list. PURPOSE: This study examined the
      effect of body-weight dosing of PSE on 800-m-run times of NCAA female runners.
      METHODS: Fifteen NCAA female track athletes volunteered to participate in the
      randomized, double-blind, crossover design. Participants were given 2.5 mg/kg PSE
      or placebo in trials separated by a week. Ninety minutes postingestion,
      participants completed an 800-m individual time trial on an indoor track.
      Finishing time was recorded with an automated video timing device. Heart rate and
      anxiety state scores were recorded immediately after each trial. RESULTS:
      Fourteen runners completed both trials, and 1 was an outlier: N=13. Despite the
      dose being well above normal therapeutic levels (144+/-17 mg), there was no
      significant difference (P=.92) in 800-m times between PSE (2:39.447+/-9.584) and
      placebo (2:39.372+/-9.636) trials, in postexercise heart rate (P=.635;
      PSE=177.9+/-14.5 beats/min, placebo=178.4+/-18.5 beats/min), or in anxiety-state
      levels (P=.650; PSE=38.4+/-11.6, placebo=38.1+/-8.8). CONCLUSION: A 2.5-mg/kg
      dose of PSE had no effect on 800-m performance for female NCAA runners. More
      research is needed to determine if PSE should be a specified banned substance.

PMID- 22158916
TI  - A facile one-step synthesis of polymer supported rhodium nanoparticles in organic
      medium and their catalytic performance in the dehydrogenation of ammonia-borane.
AB  - A new type of supported rhodium nanoparticles were reproducibly prepared from
      N(2)H(4)BH(3) reduction of [Rh(MU-Cl)(1,5-cod)](2) without using any solid
      support and pre-treatment technique. Their characterization shows the formation
      of well dispersed rhodium(0) nanoparticles within the framework of a
      polyaminoborane based polymeric support. These new rhodium(0) nanoparticles were
      found to be the most active supported catalyst in the catalytic dehydrogenation
      of ammonia-borane in water at room temperature.

PMID- 22158917
TI  - A general route for RuO2 deposition on metal oxides from RuO4.
AB  - A novel method for the deposition of RuO(2) from RuO(4)(g) on diverse metal
      oxides has been developed by grafting dopamine onto the otherwise un-reactive
      metal oxide surface. Oxygen evolution reaction on TiO(2) and the
      photoelectrochemical improvement of WO(3) by deposition of RuO(2) are just a few
      examples where this novel deposition method can be used.

PMID- 22158918
TI  - Colorimetric assay for parallel detection of Cd2+, Ni2+ and Co2+ using peptide
      modified gold nanoparticles.
AB  - A colorimetric assay has been developed for parallel detection of Cd(2+), Ni(2+)
      and Co(2+) utilizing peptide-modified gold nanoparticles (P-AuNPs) as a sensing
      element based on its unique surface plasmon resonance properties. The functional
      peptide ligand, CALNNDHHHHHH, was self-assembled on gold nanoparticles (AuNPs) to
      produce P-AuNPs probe. The P-AuNPs probe could be used to simultaneously detect
      and showed different responses to the three ions Cd(2+), Ni(2+) and Co(2+) in an
      aqueous solution based on the aggregation-induced color change of AuNPs. The
      method showed good selectivity for Cd(2+), Ni(2+) and Co(2+) over other metal
      ions, and detection limit as low as 0.05 MUM Cd(2+), 0.3 MUM Ni(2+) or 2 MUM
      Co(2+). To simultaneously (or parallel) detect the three metal ions coexisting in
      a sample, EDTA and imidazole were applied to mask Co(2+) and Ni(2+) for detecting
      Cd(2+), glutathione and EDTA were applied to mask Cd(2+) and Co(2+) for detecting
      Ni(2+), and glutathione and imidazole were applied to mask Cd(2+) and Ni(2+) for
      detecting Co(2+). Finally, the simple and cost-effective probe could be
      successfully applied for simultaneously detecting Cd(2+), Ni(2+), and Co(2+) in
      river water. Because this novel P-AgNPs-based probe design offers many
      advantages, including simplicity of preparation and manipulation compared with
      other methods that employ specific strategies, the sensing system shows potential
      application in the developing region for monitoring water quality.

PMID- 22158919
TI  - Spectrum bias: patient selection may affect performance of calcium volume in
      detecting carotid stenosis.

PMID- 22158920
TI  - Idiopathic thoracic spinal cord herniation: retrospective analysis supporting a
      mechanism of diskogenic dural injury and subsequent tamponade.
AB  - BACKGROUND AND PURPOSE: tSCH in the absence of spinal trauma or surgery is a rare
      disorder for which numerous mechanisms have been proposed. Here, we have
      conducted an analysis of images in all published reports of idiopathic tSCH and
      identified evidence supporting a pathogenesis in which anterior dural erosion at
      thoracic levels generates a CSF leak that pushes adjacent spinal tissue to
      tamponade the dural defect, causing progressive myelopathy. Additionally, we
      describe a case of tSCH in which postural headache was a significant symptom
      before myelopathy. This finding suggests that tSCH pathogenesis may be related to
      spontaneous intracranial hypotension. MATERIALS AND METHODS: Published imaging
      from all available prior case reports in the scientific literature was reviewed
      to determine whether tSCH occurred at the disk or bone level. The presence of
      EDF, HNP, or an osteophyte in the spinal canal was determined from review of
      published images. Additionally, 3 previously unreported cases from the teaching
      files of our department were assessed by using these criteria. RESULTS: In
      greater than two-thirds (47 of 67) of identified cases with published images,
      tSCH occurred at a disk level. When assessment was possible, EDF, HNP, and
      osteophytes were present in 26.8%, 30.7%, and 26.2% of cases, respectively.
      Overall, 52.3% of cases with published images demonstrated evidence of these
      abnormalities. CONCLUSIONS: Our analysis of published imaging indicates that tSCH
      occurs preferentially at spinal levels and with imaging findings consistent with
      dural injury that support the proposed etiology of this disorder.

PMID- 22158921
TI  - Intralabyrinthine schwannomas: imaging diagnosis and classification.
AB  - BACKGROUND AND PURPOSE: ILS is a rare lesion that has a different management from
      the more common "acoustic" schwannoma. To date, only 137 cases have been
      reported. We present a classification scheme based on labyrinthine anatomy to
      describe and localize these lesions. Treatment and prognosis hinge on the
      appropriate localization of these tumors; thus, a concise terminology that can be
      used by both the otolaryngologist and radiology communities is desirable.
      MATERIALS AND METHODS: After approval of the institutional review board, a
      retrospective study of all patients with the diagnosis of ILS imaged between 1996
      and 2010 was performed. Clinical and imaging data were collected. Patients were
      imaged with thin-section high-resolution T2 and contrast-enhanced MR imaging.
      RESULTS: There were 45 patients with a diagnosis of ILS. Forty-three had complete
      histories. There were 18 male and 25 female patients with an age range of 21-78
      years with a mean age of 53 years. The most common presenting symptom was
      progressive sensorineural hearing loss. Lesions were characterized on the basis
      of their location. Intracochlear was most common (14/45) followed by
      transmodiolar (13/45), intravestibular (7/45), vestibulocochlear (5/45),
      transmacular (4/45), and transotic (2/45). Sixteen patients underwent surgical
      resection. The remaining patients were followed clinically and by serial MR
      imaging. CONCLUSIONS: ILS is an uncommon but under-reported tumor. We
      characterized the MR imaging appearance of these tumors by using high-resolution
      techniques. In addition, an anatomically based classification system is presented
      that will help the radiologist accurately describe ILS within the inner ear and
      help the surgeon determine which tumors are potential surgical candidates.

PMID- 22158922
TI  - Long-term follow-up after treatment of intracranial aneurysms with the Pipeline
      embolization device: results from a single center.
AB  - BACKGROUND AND PURPOSE: Stent-like, self-expandable devices, the so-called flow
      diverters, are increasingly used for the treatment of wide-neck cerebral
      aneurysms. The immediate and short-term results are promising, but no long-term
      results are available. The purpose of our research was to report the long-term
      angiographic and cross-sectional imaging results after placement of a PED in 12
      patients with wide-neck intracranial aneurysms. MATERIALS AND METHODS: Twelve
      wide-neck or otherwise untreatable cerebral aneurysms in 12 patients were treated
      with the PED. Angiography was performed at 6 and 24 months after treatment.
      Additional MR and CT angiograms were acquired. RESULTS: In all patients,
      angiographic or cross-sectional imaging follow-up of at least 27 months
      demonstrated complete occlusion of the aneurysms treated with the PED. There were
      no cases of aneurysm recurrence. Angiography at around 6 months showed complete
      occlusion in all cases, except 1 that showed complete occlusion at the 29-month
      follow-up. In 1 patient, a clinically asymptomatic 75% in-stent stenosis was seen
      on the angiography at 6 months but was resolved completely by balloon dilation.
      Device placement was successful in all patients. Distal embolization had occurred
      in 1 patient, but the clot was resolved completely without clinical sequelae.
      Almost immediate angiographic occlusion was achieved in 2 aneurysms and flow
      reduction in 10 aneurysms. CONCLUSIONS: Treatment of wide-neck intracranial
      aneurysms by PED placement led to successful and durable occlusion in all cases,
      without severe complications. Endovascular treatment for in-stent stenosis should
      be considered cautiously, because the underlying stenosis may be transient and
      disappear within 12 months after treatment.

PMID- 22158923
TI  - Collapsing benign cystic nodules of the thyroid gland: sonographic
      differentiation from papillary thyroid carcinoma.
AB  - BACKGROUND AND PURPOSE: The US features of benign and malignant nodules overlap,
      and benign thyroid lesions can mimic thyroid malignancy on US. Benign cystic
      nodules after spontaneous collapse or needle aspiration, can mimic malignant
      thyroid nodules. Our aim was to evaluate the US features of CBCNs of the thyroid
      that distinguish such nodules from malignant thyroid nodules. MATERIALS AND
      METHODS: US and clinical findings in 13 patients, each with a single CBCN, were
      evaluated to determine if they showed >50% cystic content on initial US or CT and
      >30% decrease in maximum diameter on follow-up US. We compared these findings
      with those of 26 patients, each with a single surgically confirmed PTMC. US scans
      were analyzed for internal content, shape, margin, echogenicity, presence of
      echogenic dots suggesting micro- and macrocalcification, inner isoechoic rim, and
      low-echoic halo. RESULTS: Six of the 13 (46%) CBCNs were classified as malignant
      on US due to their marked hypoechogenicity, microcalcification, or spiculated
      margins. US features that differed between CBCNs and PTMCs were shape (ovoid-to
      round versus taller-than-wide, P = .016); margins (ill-defined versus spiculated,
      P < .000); low-echoic halo (P < .000); inner isoechoic rim (P < .000) with high
      negative predictive values (100%, 91%, 91%, and 89%, respectively); and
      clinically acceptable diagnostic accuracy (59%, 80%, 82%, and 85%, respectively).
      CONCLUSIONS: US features helpful for differential diagnosis of CBCNs from PTMCs
      include shape, margin, and the presence of an inner isoechoic rim and a low
      echoic halo. Familiarity with US features suggesting CBCNs may be helpful in
      reducing unnecessary repeated FNABs.

PMID- 22158924
TI  - Quantification of thrombus hounsfield units on noncontrast CT predicts stroke
      subtype and early recanalization after intravenous recombinant tissue plasminogen
      activator.
AB  - BACKGROUND AND PURPOSE: Little is known about the factors that determine
      recanalization after intravenous thrombolysis. We assessed the value of thrombus
      Hounsfield unit quantification as a predictive marker of stroke subtype and MCA
      recanalization after intravenous rtPA treatment. MATERIALS AND METHODS: NCCT
      scans and CTA were performed on patients with MCA acute stroke within 4.5 hours
      of symptom onset. Demographics, stroke severity, vessel hyperattenuation,
      occlusion site, thrombus length, and time to thrombolysis were recorded. Stroke
      origin was categorized as LAA, cardioembolic, or indeterminate according to TOAST
      criteria. Two blinded neuroradiologists calculated the Hounsfield unit values for
      the thrombus and contralateral MCA segment. We used ROC curves to determine the
      rHU cutoff point to discriminate patients with successful recanalization from
      those without. We assessed the accuracy (sensitivity, specificity, and positive
      and negative predictive values) of rHU in the prediction of recanalization.
      RESULTS: Of 87 consecutive patients, 45 received intravenous rtPA and only 15
      (33.3%) patients had acute recanalization. rHU values and stroke mechanism were
      the highest predictive factors of recanalization. The Matthews correlation
      coefficient was highest for rHU (0.901). The sensitivity, specificity, and
      positive and negative predictive values for lack of recanalization after
      intravenous rtPA for rHU <= 1.382 were 100%, 86.67%, 93.75%, and 100%,
      respectively. LAA thrombi had lower rHU than cardioembolic and indeterminate
      stroke thrombi (P = .004). CONCLUSIONS: The Hounsfield unit thrombus measurement
      ratio can predict recanalization with intravenous rtPA and may have clinical
      utility for endovascular treatment decision making.

PMID- 22158925
TI  - Patency of branches after coverage with multiple telescoping flow-diverter
      devices: an in vivo study in rabbits.
AB  - BACKGROUND AND PURPOSE: The safety of placing multiple overlapped endoluminal
      flow diverters remains unclear because small eloquent branch arteries
      theoretically could become occluded by these devices. We placed single and
      multiple flow diverters over small branch arteries in rabbit aortas to determine
      the incidence of branch artery occlusion. MATERIALS AND METHODS: Flow diverters
      (PED) were placed into 22 female New Zealand white rabbits abdominal aortas to
      cover >=1 lumbar artery. Animals were divided into 3 groups (single PED, n = 9;
      double PED with 2 telescoped/overlapped devices, n = 7; and triple PED, with 3
      telescoped/overlapped devices, n = 6) and were followed for 6 or 12 months. DSA
      was performed at follow-up. Subsequently, the tissue was processed, sectioned,
      and stained with H&E for histologic evaluation, histomorphometry, and analysis.
      RESULTS: All the lumbar arteries covered by devices were clearly patent on
      angiography. Partial neointima covered the ostia of the branch vessels, but
      demonstrable patent lumens at the ostia in all cases were present. Neointima
      hyperplasia was minimal in the single-PED-group animals. The measured neointima
      was thicker for the double- and triple-PED groups compared with the single-PED
      group (P < .05). However, in all groups, the mean thickness of the neointima was
      <=0.2 mm, and the percentage stenosis of the parent artery was <15% and 18% for 6
      and 12 months, respectively. There was no significant inflammatory response in
      any group. CONCLUSIONS: Small branch arteries remain patent even when covered by
      multiple overlapped PED flow-diverter devices.

PMID- 22158926
TI  - Self-referral in neuroradiology.

PMID- 22158927
TI  - Identification of venous signal on arterial spin labeling improves diagnosis of
      dural arteriovenous fistulas and small arteriovenous malformations.
AB  - BACKGROUND AND PURPOSE: DAVFs and small AVMs are difficult to detect on
      conventional MR imaging/MRA or CTA examinations and often require DSA for
      definitive diagnosis. The purpose of this study was to assess the value of venous
      signal intensity on ASL imaging for making this diagnosis. MATERIALS AND METHODS:
      Two neuroradiologists and 1 neurologist reviewed MR imaging studies in 26
      patients, 15 of whom had DSA-proved DAVFs or small (<2 cm) AVMs. Pseudocontinuous
      ASL was performed at 1.5T with background-suppressed 3D-FSE readout. Using a 5
      point scale, these readers assessed the likelihood of positive findings on a DSA
      study before and after reviewing the ASL findings. Agreement on imaging findings,
      including venous ASL signal intensity, was performed by using kappa statistics.
      Logistic regression and ROC analysis were performed to determine which imaging
      findings improved diagnosis. RESULTS: Venous ASL signal intensity was seen
      frequently in cases with positive findings on DSA. The sensitivity and
      specificity of venous ASL signal intensity for predicting positive findings on a
      DSA study were 78% and 85%, respectively. On ROC analysis, there was a
      significant increase in the AUC after review of the ASL images (AUC = 0.798 pre
      ASL, AUC = 0.891 post-ASL; P = .02). Multivariate regression identified venous
      ASL signal intensity as the strongest predictor of positive findings on a DSA
      study, with an odds ratio of 17.3 (95% CI, 3.3-90.4). CONCLUSIONS: Identifying
      venous ASL signal intensity improved detection of DAVFs and small AVMs. Attention
      to this finding may improve triage to DSA in patients with suspected small
      vascular malformations.

PMID- 22158928
TI  - Intracranial meningeal hemangiopericytomas in children and adolescents: CT and MR
      imaging findings.
AB  - Intracranial meningeal hemangiopericytomas in children and adolescents are prone
      to bleeding during surgery. CT and MR imaging may serve a role in preoperative
      diagnosis. The purpose of this report was to describe the radiologic findings in
      9 pathologically proved cases of intracranial meningeal hemangiopericytomas in
      children and adolescents. The average duration of symptoms was short (mean, 4.0
      months; median, 1.5 months). The intraoperative blood loss was large (mean, 3561
      mL; median, 1000 mL). Tumors were extra-axial, irregularly multilobular, and
      hypervascular. Radiologically, they showed mixed attenuation on precontrast CT
      images, heterogeneous signal intensity on precontrast MR imaging, and marked and
      heterogeneous enhancement on postcontrast MR imaging. Bone erosion was sometimes
      present, but hyperostosis was not present. On MR imaging, multiple signal
      intensity voids of vessels were observed in 100% (8/8) of tumors with AVM-like
      signal intensity flow voids in 25% (2/8) of tumors. These results suggest that CT
      and MR imaging findings may be helpful for preoperative diagnosis.

PMID- 22158929
TI  - A safe and efficacious alternative: sonographically guided internal jugular vein
      puncture for intracranial endovascular intervention.
AB  - Transvenous interventions for intracranial vascular lesions are usually performed
      via venous access of a femoral vein puncture. However, the transjugular route is
      an alternative with a shorter and less tortuous vascular access for intracranial
      lesions. Although puncture of the internal jugular vein is generally believed to
      be too dangerous owing to potential hazardous complications, the safety of the
      sonographically guided retrograde internal jugular vein puncture technique for
      intracranial intervention has not been fully evaluated in the English literature.
      We present our experience with a total of 44 transjugular intervention procedures
      between April 1999 and June 2010. We believe sonographically guided internal
      jugular vein puncture is a safe and efficacious technique for establishing
      transvenous access for an intracranial endovascular intervention.

PMID- 22158930
TI  - Neuroradiology back to the future: brain imaging.
AB  - The beginning of neuroradiology can be traced to the early 1900s with the use of
      skull radiographs. Ventriculography and pneumoencephalography were introduced in
      1918 and 1919, respectively, and carotid angiography, in 1927. Technical advances
      were made in these procedures during the next 40 years that lead to improved
      diagnosis of intracranial pathology. Yet, they remained invasive procedures that
      were often uncomfortable and associated with significant morbidity. The
      introduction of CT in 1971 revolutionized neuroradiology. Ventriculography and
      pneumoencephalography were rendered obsolete. The imaging revolution continued
      with the advent of MR imaging in the early 1980s. Noninvasive angiographic
      techniques have curtailed the use of conventional angiography, and physiologic
      imaging gives us a window into the function of the brain. In this historical
      review, we will trace the origin and evolution of the advances that have led to
      the quicker, less invasive diagnosis and resulted in more rapid therapy and
      improved outcomes.

PMID- 22158931
TI  - Effect of stenting on cerebral CT perfusion in symptomatic and asymptomatic
      patients with carotid artery stenosis.
AB  - BACKGROUND AND PURPOSE: The introduction of CAS has led to increased treatment of
      both symptomatic and asymptomatic patients with internal carotid stenosis. This
      study was performed to compare the effect of stent placement on cerebral
      perfusion in symptomatic and asymptomatic patients using CT perfusion. MATERIALS
      AND METHODS: We included 45 patients with carotid artery stenosis of >=70% who
      underwent arterial stent placement. Thirty-one patients were treated because of
      symptoms; 14 asymptomatic patients were treated before coronary artery bypass
      grafting. Patients underwent CTP before and after stent placement. We calculated
      MTT, CBV, and CBF, and derived relative numbers that compared treated with
      untreated hemispheres: ratios of CBV and CBF and difference in MTT. We compared
      the effect of carotid stent placement on cerebral perfusion in symptomatic and
      asymptomatic patients. RESULTS: All perfusion parameters changed significantly
      after treatment in symptomatic patients: rCBF increased from 0.81 to 0.93 (P <
      .001), rCBV decreased from 1.02 to 0.95 (P < .05), and dMTT decreased from 1.29
      to 0.14 (P < .001). In asymptomatic patients only, rCBF changed significantly
      with an increase from 0.92 to 1.03 (P < .05). When we compared symptomatic and
      asymptomatic patients before treatment, rCBF in symptomatic patients was
      significantly lower. The decrease of rCBV after treatment in symptomatic patients
      resulted in a significantly lower value than in asymptomatic patients.
      CONCLUSIONS: Carotid artery stent placement improves blood flow in the affected
      hemisphere in symptomatic and asymptomatic patients. CBF before treatment is more
      strongly impaired in patients with symptomatic carotid stenosis. Compensatory
      hyperemia on the symptomatic side before treatment (rCBV > 1) turns into
      hypoxemia after treatment, suggesting impaired autoregulation in these patients.

PMID- 22158932
TI  - Untested and undiagnosed: barriers to HIV testing among men who have sex with
      men, Beijing, China.
AB  - OBJECTIVES: Undiagnosed HIV presents great potential for the spread of infection.
      The authors identify the prevalence and correlates of never testing and being
      unaware of HIV infection in Beijing men who have sex with men (MSM). METHODS:
      Cross-sectional biological and behavioural survey using respondent-driven
      sampling; 500 MSM were included. RESULTS: HIV prevalence was 7.2% with 86.1%
      unaware of their infection; 33.2% had never tested. Never testing was associated
      with lower educational (adjusted odds ratio (AOR) 1.6, 95% CI (CI) 1.1 to 2.5),
      living in Beijing for <=3 years (AOR 1.5, 95% CI 1.0 to 2.3), unprotected anal
      intercourse with most recent male partner (AOR 1.6, 95% CI 1.0 to 2.4), being
      unaware of the most recent male partner's HIV status (AOR 3.6, 95% CI 2.1 to 6.1)
      and holding stigmatised attitudes towards persons with HIV (AOR 1.1 per scale
      point, 95% CI 1.0 to 1.1). Predictors of having undiagnosed HIV infection were
      being married (AOR 2.4, 95% CI 1.0 to 5.4), living in Beijing for <=3 years (AOR
      3.6, 95% CI 1.5 to 8.4), being unaware of the most recent male partner's HIV
      status (AOR 6.8, 95% CI 0.9 to 51.6) and holding negative attitudes towards safe
      sex (AOR 1.1 per scale point, 95% CI 1.0 to 1.1). CONCLUSIONS: Recent attention
      has focused on HIV prevention interventions that depend upon knowing one's
      serostatus, including viral load suppression, prevention with positives, pre
      exposure prophylaxis and seroadaptation. Until the low level of testing and
      resulting high level of undiagnosed HIV infection are addressed, these tools are
      not likely to be effective for MSM in China.

PMID- 22158933
TI  - The future of HIV care in the USA.
AB  - BACKGROUND: The number of people living with HIV in the USA increased by 50% to
      1.115 million persons from 1996 to 2006 and may exceed 1.5 million by 2015. The
      rising caseloads are straining the HIV care system, while recession and the
      unknown fate of health reforms are sources of uncertainty. HIV care in the USA
      evolved within a fragmented healthcare system. Unique community-based support and
      education linked to diverse multidisciplinary HIV care teams contributed to 'AIDS
      exceptionalism'. OBJECTIVE: To describe HIV care in the USA in 2011 and to
      consider future trends. METHODS: Literature review. RESULTS: Though evidence for
      effectiveness of HIV care teams is increasing, HIV care in the USA in 2011 is
      severely challenged. Low reimbursements, rising caseloads and increasing care
      complexity are leading to clinician shortages. Access to antiretrovirals through
      Medicare and Medicaid is worsening, and deficiencies in AIDS Drug Assistance
      Programs are increasing. Durable health insurance will become available for most
      Americans in 2014 through new health reforms, but the likelihood of incomplete
      coverage, fierce political opposition and the uncertain details are reasons for
      concern. At the same time, recent trends in HIV epidemiology, pathogenesis and
      care services have reinforced the need for multidisciplinary teams with strong
      community linkages. CONCLUSIONS: HIV advocates have their greatest challenge to
      date to ensure that the gains and lessons in HIV care learnt from the past are
      not lost in the transition to national health reform in the next turbulent 5
      years in the USA.

PMID- 22158934
TI  - Costs and efficiency of integrating HIV/AIDS services with other health services:
      a systematic review of evidence and experience.
AB  - OBJECTIVES: To review the literature on the potential efficiency gains of
      integrating HIV services with other health services. DESIGN: Systematic
      literature review. Search of electronic databases, manual searching and snowball
      sampling. Studies that presented results on cost, efficiency or cost
      effectiveness of integrated HIV services were included, focusing on low- and
      middle-income countries. Evidence was analysed and synthesised through a
      narrative approach and the quality of studies assessed. RESULTS: Of 666 citations
      retrieved, 46 were included (35 peer reviewed and 11 from grey literature). A
      range of integrated HIV services were found to be cost-effective compared with
      'do-nothing' alternatives, including HIV services integrated into sexual and
      reproductive health services, integrated tuberculosis/HIV services and HIV
      services integrated into primary healthcare. The cost of integrated HIV
      counselling and testing is likely to be lower than that of stand-alone
      counselling and testing provision; however, evidence is limited on the
      comparative costs of other services, particularly HIV care and treatment. There
      is also little known about the most efficient model of integration, the
      efficiency gain from integration beyond the service level and any economic
      benefit to HIV service users. CONCLUSIONS: In the context of increasing political
      commitment and previous reviews suggesting a strong public health argument for
      the integration of HIV services, the authors found the evidence on efficiency
      broadly supports further efforts to integrate HIV services. However, key evidence
      gaps remain, and there is an urgent need for further research in this area.

PMID- 22158936
TI  - Prevalence of unprotected anal intercourse and unprotected vaginal intercourse
      among HIV-positive men who have sex with men in China: a meta-analysis.
AB  - This study aims at deriving a general description of the prevalence of
      unprotected anal intercourse among HIV-positive MSM in China using published
      epidemiological research. Comprehensively searching Wanfang, Weipu, China
      Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI) and
      Pubmed databases in the systematic review. Meta-analysis were conducted over a
      final set of nineteen studies (n=1603). The pooled prevalence of unprotected anal
      intercourse among HIV-positive MSM was 75.4% (95% CI: 67.5%~82.5%) and
      unprotected vaginal intercourse was 68.0% (95% CI: 46.0%~86.4%). The prevalence
      of unprotected anal intercourse differed significantly in sampling method, data
      collection method, sample size, location, recruitment setting and data collection
      period. Studies with the following features had a higher prevalence of
      unprotected anal intercourse: recruiting participants from 2005 to 2007, sample
      size being below 50, recruiting participants from MSM venues/internet, using
      convenience sampling, study location being Chongqing city, and using interviewer
      administered questionnaire. Findings from this meta-analysis indicate that a
      majority percentage of HIV-positive MSM engage in unprotected sexual behavior. So
      that place their sex partners at risk for infecting HIV and also place themselves
      at risk for other sexually transmitted diseases. An effective strategy for
      prevention and control is required for this specific population in China.

PMID- 22158935
TI  - Trends in the incidence of HIV in Scotland, 1988-2009.
AB  - OBJECTIVES: To estimate temporal trends in HIV incidence and prevalence in
      Scotland, according to three main risk groups for infection: men who have sex
      with men (MSM), injecting drug users (IDUs) and heterosexuals. METHODS: The
      authors extracted data for all single- and multiple-tested individuals from the
      national HIV test database covering the period 1980-2009 and calculated the
      incidence of HIV infection in each risk group and estimated RRs by fitting
      Poisson regression models. RESULTS: 620 of 59,807 individuals tested positive
      following an initial negative HIV test, generating an overall incidence rate of
      3.7/1000 person-years (95% CI 3.4 to 4.0); 60%, 20% and 37% of the 620 were
      associated with the risk behaviour categories MSM, IDU and heterosexual,
      respectively. The incidence rate among MSM in Scotland remained relatively stable
      between the periods <1995 and 2005-2009 (overall: 15.3/1000 person-years, 95% CI
      13.8 to 17.0), whereas the incidence among IDUs decreased between the periods
      <1995 and 2005-2009, from 5.1/1000 to 1.7/1000 person-years, and also decreased
      among heterosexuals, from 2.9/1000 to 1.4/1000 person-years. CONCLUSIONS: The
      reduction in the incidence rate among IDUs suggests that harm reduction measures
      initiated from the late 1980s were effective in reducing HIV transmission in this
      risk group; however, the absence of a reduction in HIV incidence rates among MSM
      is disappointing and highlights the need for renewed efforts in the prevention of
      HIV in this major risk group.

PMID- 22158937
TI  - Highly enantioselective synthesis of silahelicenes using Ir-catalyzed [2+2+2]
      cycloaddition.
AB  - Silahelicenes, which contain two silole moieties in a helically chiral structure,
      were synthesized by a chiral Ir-catalyzed intermolecular [2+2+2] cycloaddition of
      tetraynes with diynes along with a Ni-mediated intramolecular [2+2+2]
      cycloaddition. The photophysical properties of the obtained highly
      enantiomerically enriched silahelicenes (up to 93% ee) were also measured.

PMID- 22158938
TI  - Evaporation-induced formation of fractal-like structures from nanofluids.
AB  - After the nanofluids are fully dried, the self-assembled nanoparticles can form
      various structures on the substrate. The fractal-like patterns are among them.
      The two-dimensional Kinetic Monte Carlo model is developed to predict the drying
      patterns of the nanofluids in an open domain, where the dewetting front shrinks
      from the edge toward the center. The simulation reveals that the initially
      dispersed particles can be deposited into an isotropic branched structure which
      remains frozen after full evaporation of the base fluid. The well-developed
      fractal-like particle aggregates are different from the fractal cavities obtained
      in the previous closed domain simulation. The present prediction of the fractal
      particle aggregation is verified by the experiments with the water-based
      nanofluids. The images taken using a scanning electron microscope prove that the
      evaporation-induced branched microstructures are formed by the nanoparticles as
      the water is totally dried.

PMID- 22158939
TI  - Classical oxidant induced chemiluminescence of fluorescent carbon dots.
AB  - We report new chemiluminescent properties of fluorescent carbon dots in the
      presence of classical oxidants, such as acidic potassium permanganate and
      cerium(IV). The radiative recombination of oxidant-injected holes and electrons
      in the carbon dots accounts for the CL emission, which sheds new light on
      characteristics of the carbon dots.

PMID- 22158941
TI  - New reactivity of the uranyl ion: ring opening polymerisation of epoxides.
AB  - The uranyl aryloxide, [UO(2)(OAr)(2)(THF)(2)], and uranyl chloride,
      [UO(2)Cl(2)(THF)(3)] or [UO(2)Cl(2)(THF)(2)](2) act as pre-catalysts for the ring
      opening polymerization of propylene oxide and cyclohexene oxide. Coordination of
      the monomers has been investigated using (1)H EXSY spectroscopy and kinetic and
      thermodynamic parameters reported. NMR analyses of the polymers suggest a
      bimetallic mechanism for the polymerization.

PMID- 22158942
TI  - A general theoretical model for electron transfer reactions in complex systems.
AB  - In this paper we present a general theoretical-computational model for treating
      electron transfer reactions in complex atomic-molecular systems. The underlying
      idea of the approach, based on unbiased first-principles calculations at the
      atomistic level, utilizes the definition and the construction of the Diabatic
      Perturbed states of the involved reactive partners (i.e. the quantum centres in
      our perturbation approach) as provided by the interaction with their environment,
      including their mutual interaction. In this way we reconstruct the true Adiabatic
      states of the reactive partners characterizing the electron transfer process as
      the fluctuation of the electronic density due to the fluctuating perturbation.
      Results obtained by using a combination of Molecular Dynamics simulation and the
      Perturbed Matrix Method on a prototypical intramolecular electron transfer (from
      2-(9,9'-dimethyl)fluorene to the 2-naphthalene group separated by a steroidal 5
      alpha-androstane skeleton) well illustrate the accuracy of the method in
      reproducing both the thermodynamics and the kinetics of the process.

PMID- 22158943
TI  - Electrodeposition of germanium from supercritical fluids.
AB  - Several Ge(II) and Ge(IV) compounds were investigated as possible reagents for
      the electrodeposition of Ge from liquid CH(3)CN and CH(2)F(2) and supercritical
      CO(2) containing as a co-solvent CH(3)CN (scCO(2)) and supercritical CH(2)F(2)
      (scCH(2)F(2)). For Ge(II) reagents the most promising results were obtained using
      [NBu(n)(4)][GeCl(3)]. However the reproducibility was poor and the reduction
      currents were significantly less than the estimated mass transport limited
      values. Deposition of Ge containing films was possible at high cathodic potential
      from [NBu(n)(4)][GeCl(3)] in liquid CH(3)CN and supercritical CO(2) containing
      CH(3)CN but in all cases they were heavily contaminated by C, O, F and Cl. Much
      more promising results were obtained using GeCl(4) in liquid CH(2)F(2) and
      supercritical CH(2)F(2). In this case the reduction currents were consistent with
      mass transport limited reduction and bulk electrodeposition produced amorphous
      films of Ge. Characterisation by XPS showed the presence of low levels of O, F
      and C, XPS confirmed the presence of Ge together with germanium oxides, and Raman
      spectroscopy showed that the as deposited amorphous Ge could be crystallised by
      the laser used in obtaining the Raman measurements.

PMID- 22158944
TI  - Nanocarriers enhance Doxorubicin uptake in drug-resistant ovarian cancer cells.
AB  - Resistance to anthracyclines and other chemotherapeutics due to P-glycoprotein
      (pgp)-mediated export is a frequent problem in cancer treatment. Here, we report
      that iron oxide-titanium dioxide core-shell nanocomposites can serve as efficient
      carriers for doxorubicin to overcome this common mechanism of drug resistance in
      cancer cells. Doxorubicin nanocarriers (DNC) increased effective drug uptake in
      drug-resistant ovarian cells. Mechanistically, doxorubicin bound to the TiO(2)
      surface by a labile bond that was severed upon acidification within cell
      endosomes. Upon its release, doxorubicin traversed the intracellular milieu and
      entered the cell nucleus by a route that evaded pgp-mediated drug export.
      Confocal and X-ray fluorescence microscopy and flow cytometry were used to show
      the ability of DNCs to modulate transferrin uptake and distribution in cells.
      Increased transferrin uptake occurred through clathrin-mediated endocytosis,
      indicating that nanocomposites and DNCs may both interfere with removal of
      transferrin from cells. Together, our findings show that DNCs not only provide an
      alternative route of delivery of doxorubicin to pgp-overexpressing cancer cells
      but also may boost the uptake of transferrin-tagged therapeutic agents.

PMID- 22158947
TI  - Targeting quiescent tumor cells via oxygen and IGF-I supplementation.
AB  - Conventional chemotherapy targets proliferating cancer cells, but most cells in
      solid tumors are not in a proliferative state. Thus, strategies to enable
      conventional chemotherapy to target noncycling cells may greatly increase tumor
      responsiveness. In this study, we used a 3-dimensional tissue culture system to
      assay diffusible factors that can limit proliferation in the context of the tumor
      microenvironment, with the goal of identifying targets to heighten proliferative
      capacity in this setting. We found that supraphysiologic levels of insulin or
      insulin-like growth factor I (IGF-I) in combination with oxygen supplementation
      were sufficient to initiate proliferation of quiescence cells in this system. At
      maximal induction with IGF-I, net tissue proliferation increased 3- to 4-fold in
      the system such that chemotherapy could trigger a 3- to 6-fold increase in
      cytotoxicity, compared with control conditions. These effects were confirmed in
      vivo in colon cancer xenograft models with demonstrations that IGF-I receptor
      stimulation was sufficient to generate a 45% increase in tumor cell
      proliferation, along with a 25% to 50% increase in chemotherapy-induced tumor
      growth delay. Although oxygen was a dominant factor limiting in vitro tumor cell
      proliferation, we found that oxygen supplementation via pure oxygen breathing at
      1 or 2 atmospheres pressure (mimicking hyperbaric therapy) did not decrease
      hypoxia in the tumor xenograft mouse model and was insufficient to increase tumor
      proliferation. Thus, our findings pointed to IGF-I receptor stimulation as a
      rational strategy to successfully increase tumor responsiveness to cytotoxic
      chemotherapy.

PMID- 22158946
TI  - Targeting protein synthesis in a Myc/mTOR-driven model of anorexia-cachexia
      syndrome delays its onset and prolongs survival.
AB  - Anorexia-cachexia syndrome (ACS) is a major determinant of cancer-related death
      that causes progressive body weight loss due to depletion of skeletal muscle mass
      and body fat. Here, we report the development of a novel preclinical murine model
      of ACS in which lymphomas harbor elevated Myc and activated mTOR signaling. The
      ACS phenotype in this model correlated with deregulated expression of a number of
      cytokines, including elevated levels of interleukin-10 which was under the direct
      translational control of mTOR. Notably, pharmacologic intervention to impair
      protein synthesis restored cytokine production to near-normal levels, delayed ACS
      progression, and extended host survival. Together, our findings suggest a new
      paradigm to treat ACS by strategies which target protein synthesis to block the
      production of procachexic factors.

PMID- 22158945
TI  - S100A7 enhances mammary tumorigenesis through upregulation of inflammatory
      pathways.
AB  - S100A7/psoriasin, a member of the epidermal differentiation complex, is widely
      overexpressed in invasive estrogen receptor (ER)alpha-negative breast cancers.
      However, it has not been established whether S100A7 contributes to breast cancer
      growth or metastasis. Here, we report the consequences of its expression on
      inflammatory pathways that impact breast cancer growth. Overexpression of human
      S100A7 or its murine homologue mS100a7a15 enhanced cell proliferation and
      upregulated various proinflammatory molecules in ERalpha-negative breast cancer
      cells. To examine in vivo effects, we generated mice with an inducible form of
      mS100a7a15 (MMTV-mS100a7a15 mice). Orthotopic implantation of MVT-1 breast tumor
      cells into the mammary glands of these mice enhanced tumor growth and metastasis.
      Compared with uninduced transgenic control mice, the mammary glands of mice where
      mS100a7a15 was induced exhibited increased ductal hyperplasia and expression of
      molecules involved in proliferation, signaling, tissue remodeling, and macrophage
      recruitment. Furthermore, tumors and lung tissues obtained from these mice showed
      further increases in prometastatic gene expression and recruitment of tumor
      associated macrophages (TAM). Notably, in vivo depletion of TAM inhibited the
      effects of mS100a7a15 induction on tumor growth and angiogenesis. Furthermore,
      introduction of soluble hS100A7 or mS100a7a15 enhanced chemotaxis of macrophages
      via activation of RAGE receptors. In summary, our work used a powerful new model
      system to show that S100A7 enhances breast tumor growth and metastasis by
      activating proinflammatory and metastatic pathways.

PMID- 22158949
TI  - Thermodynamic properties of non-conformal soft-sphere fluids with effective hard
      sphere diameters.
AB  - In this work we study a set of soft-sphere systems characterised by a well
      defined variation of their softness. These systems represent an extension of the
      repulsive Lennard-Jones potential widely used in statistical mechanics of fluids.
      This type of soft spheres is of interest because they represent quite accurately
      the effective intermolecular repulsion in fluid substances and also because they
      exhibit interesting properties. The thermodynamics of the soft-sphere fluids is
      obtained via an effective hard-sphere diameter approach that leads to a compact
      and accurate equation of state. The virial coefficients of soft spheres are shown
      to follow quite simple relationships that are incorporated into the equation of
      state. The approach followed exhibits the rescaling of the density that produces
      a unique equation for all systems and temperatures. The scaling is carried
      through to the level of the structure of the fluids.

PMID- 22158948
TI  - Transmission of HIV-1 drug resistance in Benin could jeopardise future treatment
      options.
AB  - OBJECTIVES: As access to antiretrovirals (ARV) increases in developing countries,
      the identification of optimal therapeutic regimens and prevention strategies
      requires the identification of resistance pathways in non-B subtypes as well as
      the surveillance of drug mutation resistance (SDMR) including the trafficking of
      viral strains between high-risk groups such as commercial sex workers (CSW) and
      the general population (GP). In this study, the authors evaluated the rate of
      primary resistance mutations and the epidemiological link between isolates from
      GP and CSW from Benin. METHODS: Plasma samples were obtained from 129 HIV-1
      infected treatment-naive individuals. Drug resistance mutations were identified
      using SDMR list and compared with other resistance algorithms. RESULTS: No
      nucleoside reverse transcriptase inhibitor resistance mutations were found. Four
      patients had non-nucleoside reverse transcriptase inhibitor resistance (K103N,
      G190A). One patient exhibited protease inhibitors resistance mutation, F53Y.
      Using the SDMR list, the authors obtained a rate of 3.9% of primary resistance.
      Nevertheless, the authors observed several mutations not on SDMR list but
      included in others resistance database, taking those mutations into account, the
      authors obtained a rate of 15.5%. CONCLUSIONS: Although our results show a low
      rate of SDMR, this algorithm may underestimate resistance mutations that may
      impact treatment options in developing countries. Primary resistance rates were
      similar in CSW and in the GP. Our phylogenetic analysis confirmed the genetic
      exchange between groups.

PMID- 22158950
TI  - Low absorption vitreous carbon reactors for operando XAS: a case study on
      Cu/Zeolites for selective catalytic reduction of NO(x) by NH3.
AB  - We describe the use of vitreous carbon as an improved reactor material for an
      operando X-ray absorption spectroscopy (XAS) plug-flow reactor. These tubes
      significantly broaden the operating range for operando experiments. Using
      selective catalytic reduction (SCR) of NO(x) by NH(3) on Cu/Zeolites (SSZ-13,
      SAPO-34 and ZSM-5) as an example reaction, we illustrate the high-quality XAS
      data achievable with these reactors. The operando experiments showed that in
      Standard SCR conditions of 300 ppm NO, 300 ppm NH(3), 5% O(2), 5% H(2)O, 5% CO(2)
      and balance He at 200  degrees C, the Cu was a mixture of Cu(I) and Cu(II)
      oxidation states. XANES and EXAFS fitting found the percent of Cu(I) to be 15%,
      45% and 65% for SSZ-13, SAPO-34 and ZSM-5, respectively. For Standard SCR, the
      catalytic rates per mole of Cu for Cu/SSZ-13 and Cu/SAPO-34 were about one third
      of the rate per mole of Cu on Cu/ZSM-5. Based on the apparent lack of correlation
      of rate with the presence of Cu(I), we propose that the reaction occurs via a
      redox cycle of Cu(I) and Cu(II). Cu(I) was not found in in situ SCR experiments
      on Cu/Zeolites under the same conditions, demonstrating a possible pitfall of in
      situ measurements. A Cu/SiO(2) catalyst, reduced in H(2) at 300  degrees C, was
      also used to demonstrate the reactor's operando capabilities using a bending
      magnet beamline. Analysis of the EXAFS data showed the Cu/SiO(2) catalyst to be
      in a partially reduced Cu metal-Cu(I) state. In addition to improvements in data
      quality, the reactors are superior in temperature, stability, strength and ease
      of use compared to previously proposed borosilicate glass, polyimide tubing,
      beryllium and capillary reactors. The solid carbon tubes are non-porous,
      machinable, can be operated at high pressure (tested at 25 bar), are inert, have
      high material purity and high X-ray transmittance.

PMID- 22158951
TI  - Papillary thyroid carcinoma-like tumor of the kidney: a case report.
AB  - Thyroid carcinoma-like tumor of the kidney is an extremely rare variant of renal
      cell carcinoma. Most previously reported cases were incidental finding; and none
      of them showed papillary thyroid carcinoma (PTC) nuclear features. This study
      reports the first case of PTC (follicular variant)-like tumor of the kidney in
      which a female patient presented with hematuria, weight loss, and flank pain.
      Imaging studies revealed a left renal mass with enlarged hilar lymph nodes.
      Histologically, the renal tumor had a striking resemblance to follicular variant
      of PTC. However, no radiological abnormalities were found in the thyroid,
      mediastinum, or pelvis. Tumor cells were negative for thyroid markers
      (thyroglobulin and TTF1). According to the authors, this is the first case of PTC
      (follicular variant)-like tumor of the kidney.

PMID- 22158952
TI  - Division of labour and the evolution of multicellularity.
AB  - Understanding the emergence and evolution of multicellularity and cellular
      differentiation is a core problem in biology. We develop a quantitative model
      that shows that a multicellular form emerges from genetically identical
      unicellular ancestors when the compartmentalization of poorly compatible
      physiological processes into component cells of an aggregate produces a fitness
      advantage. This division of labour between the cells in the aggregate occurs
      spontaneously at the regulatory level owing to mechanisms present in unicellular
      ancestors and does not require any genetic predisposition for a particular role
      in the aggregate or any orchestrated cooperative behaviour of aggregate cells.
      Mathematically, aggregation implies an increase in the dimensionality of
      phenotype space that generates a fitness landscape with new fitness maxima, in
      which the unicellular states of optimized metabolism become fitness saddle
      points. Evolution of multicellularity is modelled as evolution of a hereditary
      parameter: the propensity of cells to stick together, which determines the
      fraction of time a cell spends in the aggregate form. Stickiness can increase
      evolutionarily owing to the fitness advantage generated by the division of labour
      between cells in an aggregate.

PMID- 22158953
TI  - Epistasis can lead to fragmented neutral spaces and contingency in evolution.
AB  - In evolution, the effects of a single deleterious mutation can sometimes be
      compensated for by a second mutation which recovers the original phenotype. Such
      epistatic interactions have implications for the structure of genome space-
      namely, that networks of genomes encoding the same phenotype may not be connected
      by single mutational moves. We use the folding of RNA sequences into secondary
      structures as a model genotype-phenotype map and explore the neutral spaces
      corresponding to networks of genotypes with the same phenotype. In most of these
      networks, we find that it is not possible to connect all genotypes to one another
      by single point mutations. Instead, a network for a phenotypic structure with n
      bonds typically fragments into at least 2(n) neutral components, often of similar
      size. While components of the same network generate the same phenotype, they show
      important variations in their properties, most strikingly in their evolvability
      and mutational robustness. This heterogeneity implies contingency in the
      evolutionary process.

PMID- 22158954
TI  - Experimental taphonomy of giant sulphur bacteria: implications for the
      interpretation of the embryo-like Ediacaran Doushantuo fossils.
AB  - The Ediacaran Doushantuo biota has yielded fossils interpreted as eukaryotic
      organisms, either animal embryos or eukaryotes basal or distantly related to
      Metazoa. However, the fossils have been interpreted alternatively as giant
      sulphur bacteria similar to the extant Thiomargarita. To test this hypothesis,
      living and decayed Thiomargarita were compared with Doushantuo fossils and
      experimental taphonomic pathways were compared with modern embryos. In the
      fossils, as in eukaryotic cells, subcellular structures are distributed
      throughout cell volume; in Thiomargarita, a central vacuole encompasses
      approximately 98 per cent cell volume. Key features of the fossils, including
      putative lipid vesicles and nuclei, complex envelope ornament, and ornate outer
      vesicles are incompatible with living and decay morphologies observed in
      Thiomargarita. Microbial taphonomy of Thiomargarita also differed from that of
      embryos. Embryo tissues can be consumed and replaced by bacteria, forming a
      replica composed of a three-dimensional biofilm, a stable fabric for potential
      fossilization. Vacuolated Thiomargarita cells collapse easily and do not provide
      an internal substrate for bacteria. The findings do not support the hypothesis
      that giant sulphur bacteria are an appropriate interpretative model for the
      embryo-like Doushantuo fossils. However, sulphur bacteria may have mediated
      fossil mineralization and may provide a potential bacterial analogue for other
      macroscopic Precambrian remains.

PMID- 22158955
TI  - Phylogenetic relatedness as a tool in restoration ecology: a meta-analysis.
AB  - Biotic interactions assembling plant communities can be positive (facilitation)
      or negative (competition) and operate simultaneously. Facilitative interactions
      and posterior competition are among the mechanisms triggering succession, thus
      representing a good scenario for ecological restoration. As distantly related
      species tend to have different phenotypes, and therefore different ecological
      requirements, they can coexist, maximizing facilitation and minimizing
      competition. We suggest including phylogenetic relatedness together with
      phenotypic information as a predictor for the net effects of the balance between
      facilitation and competition in nurse-based restoration experiments. We quantify,
      by means of a Bayesian meta-analysis of nurse-based restoration experiments
      performed worldwide, the importance of phylogenetic relatedness and life-form
      disparity in the survival, growth and density of facilitated plants. We find that
      the more similar the life forms of neighbouring plants are the greater the
      positive effect of phylogenetic distance is on survival and density. This result
      suggests that other characteristics beyond life form are also contained in the
      phylogeny, and the larger the phylogenetic distance, the less is the niche
      overlap, and therefore the less is the competition. As a general rule, we can
      maximize the success of the nurse-based practices by increasing life-form
      disparity and phylogenetic distances between the neighbour and the facilitated
      plant.

PMID- 22158956
TI  - Brood parasite eggs enhance egg survivorship in a multiply parasitized host.
AB  - Despite the costs to avian parents of rearing brood parasitic offspring, many
      species do not reject foreign eggs from their nests. We show that where multiple
      parasitism occurs, rejection itself can be costly, by increasing the risk of host
      egg loss during subsequent parasite attacks. Chalk-browed mockingbirds (Mimus
      saturninus) are heavily parasitized by shiny cowbirds (Molothrus bonariensis),
      which also puncture eggs in host nests. Mockingbirds struggle to prevent cowbirds
      puncturing and laying, but seldom remove cowbird eggs once laid. We filmed
      cowbird visits to nests with manipulated clutch compositions and found that
      mockingbird eggs were more likely to escape puncture the more cowbird eggs
      accompanied them in the clutch. A Monte Carlo simulation of this 'dilution
      effect', comparing virtual hosts that systematically either reject or accept
      parasite eggs, shows that acceptors enjoy higher egg survivorship than rejecters
      in host populations where multiple parasitism occurs. For mockingbirds or other
      hosts in which host nestlings fare well in parasitized broods, this benefit might
      be sufficient to offset the fitness cost of rearing parasite chicks, making egg
      acceptance evolutionarily stable. Thus, counterintuitively, high intensities of
      parasitism might decrease or even reverse selection pressure for host defence via
      egg rejection.

PMID- 22158957
TI  - Fitness consequences of centrality in mutualistic individual-based networks.
AB  - The relationships among the members of a population can be visualized using
      individual networks, where each individual is a node connected to each other by
      means of links describing the interactions. The centrality of a given node
      captures its importance within the network. We hypothesize that in mutualistic
      networks, the centrality of a node should benefit its fitness. We test this idea
      studying eight individual-based networks originated from the interaction between
      Erysimum mediohispanicum and its flower visitors. In these networks, each plant
      was considered a node and was connected to conspecifics sharing flower visitors.
      Centrality indicates how well connected is a given E. mediohispanicum individual
      with the rest of the co-occurring conspecifics because of sharing flower
      visitors. The centrality was estimated by three network metrics: betweenness,
      closeness and degree. The complex relationship between centrality, phenotype and
      fitness was explored by structural equation modelling. We found that the
      centrality of a plant was related to its fitness, with plants occupying central
      positions having higher fitness than those occupying peripheral positions. The
      structural equation models (SEMs) indicated that the centrality effect on fitness
      was not merely an effect of the abundance of visits and the species richness of
      visitors. Centrality has an effect even when simultaneously accounting for these
      predictors. The SEMs also indicated that the centrality effect on fitness was
      because of the specific phenotype of each plant, with attractive plants occupying
      central positions in networks, in relation to the distribution of conspecific
      phenotypes. This finding suggests that centrality, owing to its dependence on
      social interactions, may be an appropriate surrogate for the interacting
      phenotype of individuals.

PMID- 22158958
TI  - Probability of successful larval dispersal declines fivefold over 1 km in a coral
      reef fish.
AB  - A central question of marine ecology is, how far do larvae disperse? Coupled
      biophysical models predict that the probability of successful dispersal declines
      as a function of distance between populations. Estimates of genetic isolation-by
      distance and self-recruitment provide indirect support for this prediction. Here,
      we conduct the first direct test of this prediction, using data from the well
      studied system of clown anemonefish (Amphiprion percula) at Kimbe Island, in
      Papua New Guinea. Amphiprion percula live in small breeding groups that inhabit
      sea anemones. These groups can be thought of as populations within a
      metapopulation. We use the x- and y-coordinates of each anemone to determine the
      expected distribution of dispersal distances (the distribution of distances
      between each and every population in the metapopulation). We use parentage
      analyses to trace recruits back to parents and determine the observed
      distribution of dispersal distances. Then, we employ a logistic model to (i)
      compare the observed and expected dispersal distance distributions and (ii)
      determine the relationship between the probability of successful dispersal and
      the distance between populations. The observed and expected dispersal distance
      distributions are significantly different (p < 0.0001). Remarkably, the
      probability of successful dispersal between populations decreases fivefold over 1
      km. This study provides a framework for quantitative investigations of larval
      dispersal that can be applied to other species. Further, the approach facilitates
      testing biological and physical hypotheses for the factors influencing larval
      dispersal in unison, which will advance our understanding of marine population
      connectivity.

PMID- 22158959
TI  - Social preferences based on sexual attractiveness: a female strategy to reduce
      male sexual attention.
AB  - Male sexual harassment of females is common across sexually reproducing species
      and can result in fitness costs to females. We hypothesized that females can
      reduce unwanted male attention by constructing a social niche where their female
      associates are more sexually attractive than themselves, thus influencing the
      decision-making of males to their advantage. We tested this hypothesis in the
      Trinidadian guppy (Poecilia reticulata), a species with high levels of male
      sexual harassment. First, we confirmed that non-receptive females were harassed
      less when they were paired with a more sexually attractive (receptive) female
      than with another non-receptive female. We then found that, indeed, females
      exploit this as a strategy to reduce sexual harassment; non-receptive females
      actively preferred to associate with receptive over non-receptive females.
      Importantly, when given access only to chemosensory cues, non-receptive females
      still showed this preference, suggesting that they use information from chemical
      cues to assess the sexual attractiveness of potential female partners. Receptive
      females in contrast showed no such preferences. Our results demonstrate that
      females can decrease male harassment by associating with females that are more
      sexually attractive than themselves and that they perform active partner choices
      based on this relative attractiveness. We propose that this strategy is likely to
      represent an important pathway by which females can construct social niches that
      influence the decision-making of others to their advantage; in this case, to
      reduce the sexual harassment they experience.

PMID- 22158960
TI  - Metabolic cold adaptation in fishes occurs at the level of whole animal,
      mitochondria and enzyme.
AB  - Metabolic cold adaptation (MCA), the hypothesis that species from cold climates
      have relatively higher metabolic rates than those from warm climates, was first
      proposed nearly 100 years ago and remains one of the most controversial
      hypotheses in physiological ecology. In the present study, we test the MCA
      hypothesis in fishes at the level of whole animal, mitochondria and enzyme. In
      support of the MCA hypothesis, we find that when normalized to a common
      temperature, species with ranges that extend to high latitude (cooler climates)
      have high aerobic enzyme (citrate synthase) activity, high rates of mitochondrial
      respiration and high standard metabolic rates. Metabolic compensation for the
      global temperature gradient is not complete however, so when measured at their
      habitat temperature species from high latitude have lower absolute rates of
      metabolism than species from low latitudes. Evolutionary adaptation and thermal
      plasticity are therefore insufficient to completely overcome the acute
      thermodynamic effects of temperature, at least in fishes.

PMID- 22158961
TI  - Selection for mitonuclear co-adaptation could favour the evolution of two sexes.
AB  - Mitochondria are descended from free-living bacteria that were engulfed by
      another cell between one and a half to two billion years ago. A redistribution of
      DNA led to most genetic information being lost or transferred to a large central
      genome in the nucleus, leaving a residual genome in each mitochondrion. Oxidative
      phosphorylation, the most critical function of mitochondria, depends on the
      functional compatibility of proteins encoded by both the nucleus and
      mitochondria. We investigate whether selection for adaptation between the nuclear
      and mitochondrial genomes (mitonuclear co-adaptation) could, in principle, have
      promoted uniparental inheritance of mitochondria and thereby the evolution of two
      mating types or sexes. Using a mathematical model, we explore the importance of
      the radical differences in ploidy levels, sexual and asexual modes of
      inheritance, and mutation rates of the nucleus and mitochondria. We show that the
      major features of mitochondrial inheritance, notably uniparental inheritance and
      bottlenecking, enhance the co-adaptation of mitochondrial and nuclear genes and
      therefore improve fitness. We conclude that, under a wide range of conditions,
      selection for mitonuclear co-adaptation favours the evolution of two distinct
      mating types or sexes in sexual species.

PMID- 22158962
TI  - Biomolecular interactions and tools for their recognition: focus on the quartz
      crystal microbalance and its diverse surface chemistries and applications.
AB  - Interactions between molecules are ubiquitous and occur in our bodies, the food
      we eat, the air we breathe, and myriad additional contexts. Although numerous
      tools are available for the recognition of biomolecular interactions, such tools
      are often limited in their sensitivity, expensive, and difficult to modify for
      various uses. In contrast, the quartz crystal microbalance (QCM) has sub-nanogram
      detection capabilities, is label-free, is inexpensive to create, and can be
      readily modified with a number of diverse surface chemistries to detect and
      characterize diverse interactions. To maximize the versatility of the QCM,
      scientists need to know available methods by which QCM surfaces can be modified.
      Therefore, in addition to summarizing the various tools currently used for
      biomolecular recognition, explicating the fundamental principles of the QCM as a
      tool for biomolecular recognition, and comparing the QCM with other acoustic
      sensors, we systematically review the numerous types of surface chemistries
      including hydrophobic bonds, ionic bonds, hydrogen bonds, self-assembled
      monolayers, plasma-polymerized films, photochemistry, and sensing ionic liquids
      used to functionalize QCMs for various purposes. We also review the QCM's diverse
      applications, which include the detection of gaseous species, detection of
      carbohydrates, detection of nucleic acids, detection of non-enzymatic proteins,
      characterization of enzymatic activity, detection of antigens and antibodies,
      detection of cells, and detection of drugs. Finally, we discuss the ultimate
      goals of and potential barriers to the development of future QCMs.

PMID- 22158963
TI  - Genome-wide profiling of liver X receptor, retinoid X receptor, and peroxisome
      proliferator-activated receptor alpha in mouse liver reveals extensive sharing of
      binding sites.
AB  - The liver X receptors (LXRs) are nuclear receptors that form permissive
      heterodimers with retinoid X receptor (RXR) and are important regulators of lipid
      metabolism in the liver. We have recently shown that RXR agonist-induced
      hypertriglyceridemia and hepatic steatosis in mice are dependent on LXRs and
      correlate with an LXR-dependent hepatic induction of lipogenic genes. To further
      investigate the roles of RXR and LXR in the regulation of hepatic gene
      expression, we have mapped the ligand-regulated genome-wide binding of these
      factors in mouse liver. We find that the RXR agonist bexarotene primarily
      increases the genomic binding of RXR, whereas the LXR agonist T0901317 greatly
      increases both LXR and RXR binding. Functional annotation of putative direct LXR
      target genes revealed a significant association with classical LXR-regulated
      pathways as well as peroxisome proliferator-activated receptor (PPAR) signaling
      pathways, and subsequent chromatin immunoprecipitation-sequencing (ChIP-seq)
      mapping of PPARalpha binding demonstrated binding of PPARalpha to 71 to 88% of
      the identified LXR-RXR binding sites. The combination of sequence analysis of
      shared binding regions and sequential ChIP on selected sites indicate that LXR
      RXR and PPARalpha-RXR bind to degenerate response elements in a mutually
      exclusive manner. Together, our findings suggest extensive and unexpected cross
      talk between hepatic LXR and PPARalpha at the level of binding to shared genomic
      sites.

PMID- 22158964
TI  - Integration of Elf-4 into stem/progenitor and erythroid regulatory networks
      through locus-wide chromatin studies coupled with in vivo functional validation.
AB  - The ETS transcription factor Elf-4 is an important regulator of hematopoietic
      stem cell (HSC) and T cell homeostasis. To gain insights into the transcriptional
      circuitry within which Elf-4 operates, we used comparative sequence analysis
      coupled with chromatin immunoprecipitation (ChIP) with microarray technology
      (ChIP-chip) assays for specific chromatin marks to identify three promoters and
      two enhancers active in hematopoietic and endothelial cell lines. Comprehensive
      functional validation of each of these regulatory regions in transgenic mouse
      embryos identified a tissue-specific enhancer (-10E) that displayed activity in
      fetal liver, dorsal aorta, vitelline vessels, yolk sac, and heart. Integration of
      a ChIP-sequencing (ChIP-Seq) data set for 10 key stem cell transcription factors
      showed Pu.1, Fli-1, and Erg were bound to the -10E element, and mutation of three
      highly conserved ETS sites within the enhancer abolished its activity. Finally,
      the transcriptional repressor Gfi1b was found to bind to and repress one of the
      Elf-4 promoters (-30P), and we show that this repression of Elf-4 is important
      for the maturation of primary fetal liver erythroid cells. Taken together, our
      results provide a comprehensive overview of the transcriptional control of Elf-4
      within the hematopoietic system and, thus, integrate Elf-4 into the wider
      transcriptional regulatory networks that govern hematopoietic development.

PMID- 22158965
TI  - Mannose 6 dephosphorylation of lysosomal proteins mediated by acid phosphatases
      Acp2 and Acp5.
AB  - Mannose 6-phosphate (Man6P) residues represent a recognition signal required for
      efficient receptor-dependent transport of soluble lysosomal proteins to
      lysosomes. Upon arrival, the proteins are rapidly dephosphorylated. We used mice
      deficient for the lysosomal acid phosphatase Acp2 or Acp5 or lacking both
      phosphatases (Acp2/Acp5(-/-)) to examine their role in dephosphorylation of Man6P
      containing proteins. Two-dimensional (2D) Man6P immunoblot analyses of tyloxapol
      purified lysosomal fractions revealed an important role of Acp5 acting in concert
      with Acp2 for complete dephosphorylation of lysosomal proteins. The most abundant
      lysosomal substrates of Acp2 and Acp5 were identified by Man6P affinity
      chromatography and mass spectrometry. Depending on the presence of Acp2 or Acp5,
      the isoelectric point of the lysosomal cholesterol-binding protein Npc2 ranged
      between 7.0 and 5.4 and may thus regulate its interaction with negatively charged
      lysosomal membranes at acidic pH. Correspondingly, unesterified cholesterol was
      found to accumulate in lysosomes of cultured hepatocytes of Acp2/Acp5(-/-) mice.
      The data demonstrate that dephosphorylation of Man6P-containing lysosomal
      proteins requires the concerted action of Acp2 and Acp5 and is needed for
      hydrolysis and removal of degradation products.

PMID- 22158967
TI  - Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf
      proteins.
AB  - Embryogenesis is a period during which cells are exposed to dynamic changes of
      various intracellular and extracellular stresses. Oxidative stress response genes
      are regulated by heterodimers composed of Cap'n'Collar (CNC) and small Maf
      proteins (small Mafs) that bind to antioxidant response elements (ARE). Whereas
      CNC factors have been shown to contribute to the expression of ARE-dependent
      cytoprotective genes during embryogenesis, the specific contribution of small Maf
      proteins to such gene regulation remains to be fully examined. To delineate the
      small Maf function in vivo, in this study we examined mice lacking all three
      small Mafs (MafF, MafG, and MafK). The small Maf triple-knockout mice developed
      normally until embryonic day 9.5 (E9.5). Thereafter, however, the triple-knockout
      embryos showed severe growth retardation and liver hypoplasia, and the embryos
      died around E13.5. ARE-dependent cytoprotective genes were expressed normally in
      E10.5 triple-knockout embryos, but the expression was significantly reduced in
      the livers of E13.5 mutant embryos. Importantly, the embryonic lethality could be
      completely rescued by transgenic expression of exogenous MafG under MafG gene
      regulatory control. These results thus demonstrate that small Maf proteins are
      indispensable for embryonic development after E9.5, especially for liver
      development, but early embryonic development does not require small Mafs.

PMID- 22158966
TI  - TCERG1 regulates alternative splicing of the Bcl-x gene by modulating the rate of
      RNA polymerase II transcription.
AB  - Complex functional coupling exists between transcriptional elongation and pre
      mRNA alternative splicing. Pausing sites and changes in the rate of transcription
      by RNA polymerase II (RNAPII) may therefore have fundamental impacts in the
      regulation of alternative splicing. Here, we show that the elongation and
      splicing-related factor TCERG1 regulates alternative splicing of the apoptosis
      gene Bcl-x in a promoter-dependent manner. TCERG1 promotes the splicing of the
      short isoform of Bcl-x (Bcl-x(s)) through the SB1 regulatory element located in
      the first half of exon 2. Consistent with these results, we show that TCERG1
      associates with the Bcl-x pre-mRNA. A transcription profile analysis revealed
      that the RNA sequences required for the effect of TCERG1 on Bcl-x alternative
      splicing coincide with a putative polymerase pause site. Furthermore, TCERG1
      modifies the impact of a slow polymerase on Bcl-x alternative splicing. In
      support of a role for an elongation mechanism in the transcriptional control of
      Bcl-x alternative splicing, we found that TCERG1 modifies the amount of pre-mRNAs
      generated at distal regions of the endogenous Bcl-x. Most importantly, TCERG1
      affects the rate of RNAPII transcription of endogenous human Bcl-x. We propose
      that TCERG1 modulates the elongation rate of RNAPII to relieve pausing, thereby
      activating the proapoptotic Bcl-x(S) 5' splice site.

PMID- 22158968
TI  - Intersectin 1 enhances Cbl ubiquitylation of epidermal growth factor receptor
      through regulation of Sprouty2-Cbl interaction.
AB  - Ubiquitylation of receptor tyrosine kinases plays a critical role in regulating
      the trafficking and lysosomal degradation of these important signaling molecules.
      We identified the multidomain scaffolding protein intersectin 1 (ITSN1) as an
      important regulator of this process (N. P. Martin et al., Mol. Pharmacol. 70:1463
      1653, 2006) ITSN1 stimulates ubiquitylation of the epidermal growth factor
      receptor (EGFR) through enhancing the activity of the Cbl E3 ubiquitin ligase.
      However, the precise mechanism through which ITSN1 enhances Cbl activity was
      unclear. In this study, we found that ITSN1 enhances Cbl activity through
      disrupting the interaction of Cbl with the Sprouty2 (Spry2) inhibitory protein.
      We demonstrate that ITSN1 binds Pro-rich regions in both Cbl and Spry2 and that
      interaction of ITSN1 with Spry2 disrupts Spry2-Cbl interaction, resulting in
      enhanced ubiquitylation of the EGFR. Disruption of ITSN1 binding to Spry2 through
      point mutation of the Pro-rich ITSN1 binding site in Spry2 results in enhanced
      Cbl-Spry2 interaction and inhibition of receptor ubiquitylation. This study
      demonstrates that ITSN1 enhances Cbl activity by modulating the interaction of
      Cbl with Spry2. In addition, our results reveal a new level of complexity in the
      regulation of Cbl through the interaction with ITSN1 and Spry2.

PMID- 22158969
TI  - Myocardial ATGL overexpression decreases the reliance on fatty acid oxidation and
      protects against pressure overload-induced cardiac dysfunction.
AB  - Alterations in myocardial triacylglycerol content have been associated with poor
      left ventricular function, suggesting that enzymes involved in myocardial
      triacylglycerol metabolism play an important role in regulating contractile
      function. Myocardial triacylglycerol catabolism is mediated by adipose
      triglyceride lipase (ATGL), which is rate limiting for triacylglycerol
      hydrolysis. To address the influence of triacylglycerol hydrolysis on myocardial
      energy metabolism and function, we utilized mice with cardiomyocyte-specific ATGL
      overexpression (MHC-ATGL). Biochemical examination of MHC-ATGL hearts revealed
      chronically reduced myocardial triacylglycerol content but unchanged levels of
      long-chain acyl coenzyme A esters, ceramides, and diacylglycerols. Surprisingly,
      fatty acid oxidation rates were decreased in ex vivo perfused working hearts from
      MHC-ATGL mice, which was compensated by increased rates of glucose oxidation.
      Interestingly, reduced myocardial triacylglycerol content was associated with
      moderately enhanced in vivo systolic function in MHC-ATGL mice and increased
      isoproterenol-induced cell shortening of isolated primary cardiomyocytes. Most
      importantly, MHC-ATGL mice were protected from pressure overload-induced systolic
      dysfunction and detrimental structural remodeling following transverse aortic
      constriction. Overall, this study shows that ATGL overexpression is sufficient to
      alter myocardial energy metabolism and improve cardiac function.

PMID- 22158970
TI  - Glucocorticoid-dependent phosphorylation of the transcriptional coregulator
      GRIP1.
AB  - Much of the regulatory diversity in eukaryotic transcription is provided by
      coregulators, which are recruited by DNA-binding factors to propagate signaling
      to basal machinery or chromatin. p160 family members, including the
      glucocorticoid receptor (GR)-interacting protein 1 (GRIP1), function as
      coactivators for GR, a ligand-dependent transcription factor of the nuclear
      receptor superfamily. Unlike other p160s, GRIP1 also potentiates GR-mediated
      repression of AP1 and NF-kappaB targets and, surprisingly, transcriptional
      activation by interferon regulatory factors. What enables GRIP1 activating or
      repressing properties or discrimination between physiologically antagonistic
      pathways is unknown. We found that endogenous GRIP1 in mammalian cells undergoes
      glucocorticoid-induced, GR interaction-dependent phosphorylation and identified
      one constitutive and six inducible phosphorylation sites and two putative GRIP1
      kinases, casein kinase 2 and cyclin-dependent kinase 9. We raised phosphospecific
      antibodies to the four closely spaced sites in a previously uncharacterized part
      of GRIP1 which, combined with mutagenesis, revealed the conservation of GRIP1
      phosphorylation across several cell types and species and its functional
      relevance to GR-activated transcription and to response element-specific
      recruitment of phospho-GRIP1 to native GR targets. We propose that cofactor
      engagement by GR is neither passive nor stochastic; rather, GR actively imparts
      modifications that dictate GRIP1 function in a subset of complexes, adding a
      layer of specificity to GR transcriptional control.

PMID- 22158972
TI  - Hybridization of graphene oxide and carbon nanotubes at the liquid/air interface.
AB  - The liquid/air interface provides an ideal platform for the uniform hybridization
      of multi-components in a thin graphene-based membrane through self-assembly. This
      study presents the first example for such a hybrid membrane which combines
      chemically active GO layers with highly conductive carbon nanotubes.

PMID- 22158971
TI  - Dynamic, sex-differential STAT5 and BCL6 binding to sex-biased, growth hormone
      regulated genes in adult mouse liver.
AB  - Sex-dependent pituitary growth hormone (GH) secretory patterns determine the sex
      biased expression of >1,000 genes in mouse and rat liver, affecting lipid and
      drug metabolism, inflammation, and disease. A fundamental biological question is
      how robust differential expression can be achieved for hundreds of sex-biased
      genes simply based on the GH input signal pattern: pulsatile GH stimulation in
      males versus near-continuous GH exposure in females. STAT5 is an essential
      transcriptional mediator of the sex-dependent effects of GH in the liver, but the
      mechanisms that underlie its sex-dependent actions are obscure. Here we elucidate
      the dynamic, sex-dependent binding of STAT5 and the GH/STAT5-regulated repressor
      BCL6 to mouse liver chromatin genome wide, revealing a counteractive interplay
      between these two regulators of sex differences in liver gene expression. Our
      findings establish a close correlation between sex-dependent STAT5 binding and
      sex-biased target gene expression. Moreover, sex-dependent STAT5 binding
      correlated positively with sex-biased DNase hypersensitivity and H3-K4me1 and H3
      K4me3 (activating) marks, correlated negatively with sex-biased H3-K27me3
      (repressive) marks, and was associated with sex-differentially enriched motifs
      for HNF6/CDP factors. Importantly, BCL6 binding was preferentially associated
      with repression of female-biased STAT5 targets in male liver. Furthermore, BCL6
      and STAT5 common targets but not BCL6 unique targets showed strong enrichment for
      lipid and drug metabolism. These findings provide a comprehensive, genome-wide
      view of the mechanisms whereby these two GH-regulated transcription factors
      establish and maintain sex differences affecting liver physiology and disease.
      The approaches used here to characterize sex-dependent STAT5 and BCL6 binding can
      be applied to other condition-specific regulatory factors and binding sites and
      their interplay with cooperative chromatin binding factors.

PMID- 22158973
TI  - The statistical evolution of multiple generations of oxidation products in the
      photochemical aging of chemically reduced organic aerosol.
AB  - The heterogeneous reactions of hydroxyl radicals (OH) with squalane and bis(2
      ethylhexyl) sebacate (BES) particles are used as model systems to examine how
      distributions of reaction products evolve during the oxidation of chemically
      reduced organic aerosol. A kinetic model of multigenerational chemistry, which is
      compared to previously measured (squalane) and new (BES) experimental data,
      reveals that it is the statistical mixtures of different generations of oxidation
      products that control the average particle mass and elemental composition during
      the reaction. The model suggests that more highly oxidized reaction products,
      although initially formed with low probability, play a large role in the
      production of gas phase reaction products. In general, these results highlight
      the importance of considering atmospheric oxidation as a statistical process,
      further suggesting that the underlying distribution of molecules could play
      important roles in aerosol formation as well as in the evolution of key
      physicochemical properties such as volatility and hygroscopicity.

PMID- 22158974
TI  - First example of a Cu(I)-(eta2-O,O)nitrite complex derived from Cu(II)-nitrosyl.
AB  - Copper(II) complex, 1, of the bidentate ligand, L [L = bis(2-ethyl-4-methyl
      imidazol-5yl)methane] has been synthesized and structurally characterized.
      Addition of nitric oxide gas to a degassed acetonitrile solution of 1 yielded the
      corresponding copper(ii)-nitrosyl complex, 2. In acetonitrile, complex 2 on
      reaction with water afforded the corresponding copper(I)-nitrite complex, 3.
      Single crystal structure of complex 3 reveals the bidentate nitrite (eta(2)-O,O)
      bonding. This is the first example of a structurally characterized Cu(I)-(eta(2)
      O,O)nitrite complex with N-donor ligand. The sequence of the formation of these
      complexes is just the reverse of the key steps of the postulated nitrite
      reduction cycle by CuNiRs.

PMID- 22158976
TI  - Schizophrenia: is the concept disintegrating?

PMID- 22158978
TI  - Is it possible to model psychotic states in animals?

PMID- 22158977
TI  - Effects of amphetamine and pimozide on reinforcement and motor parameters in
      variable-interval performance.
AB  - The effects of amphetamine and pimozide were studied in rats performing on
      variable-interval (VI) schedules of reinforcement. In experiment 1, a five
      component multiple VI schedule was used; in experiments 2 and 3, two VI schedules
      were presented on alternate days; a fourth experiment was carried out to validate
      the two VI methods. The Herrnstein matching law was used to distinguish between
      changes in reinforcer efficacy and changes in motor capacity. In both procedures,
      amphetamine, at 0.5 mg/kg, caused changes compatible with an increase in
      reinforcer efficacy with no change in motor capacity; higher doses (only tested
      in the multiple schedule) appeared further to increase reinforcer efficacy and
      also to decrease motor capacity. In the multiple schedule, pimozide caused
      changes compatible with either a decrease in reinforcer efficacy or a decrease in
      motor capacity, depending on the order of presentation of the schedule
      components; in the alternating schedule, pimozide had both effects. These
      discrepancies appeared to be due to changes in the effect of pimozide over time,
      which could not be explained either by satiation or by a gradual onset of drug
      action.

PMID- 22158979
TI  - Pharmacological characterization in the rat of grooming and other behavioural
      responses to the D1 dopamine receptor agonist R-SK&F 38393.
AB  - Grooming, sniffing, Iocomotor and rearing responses to the D(1) dopamine receptor
      agonist SK&F 38393, as the racemic compound or its R-enantiomer, were
      characterized pharmacologically using typical neuroleptics, non-dopaminergic
      antagonists, selective D(1) antagonists and selective D(2) antagonists. The
      typical neuroleptics haloperidol and flupenthixol blocked all behaviours induced
      by SK&F 38393; this action of flupenthixol was stereoselective for its cis(Z)
      isomer but not its trans(E)-isomer. Non-dopaminergic antagonists failed to
      reproduce the consistent effects of typical neuroleptics. The selective D(1)
      antagonist SCH 23390 potently blocked all responses to SK&F 38393. A related
      selective D(1) antagonist, SK&F 83566, also blocked these responses, and this
      action was stereoselective for its R-enantiomer but not its S-enantiomer. These
      data suggest that D(1) receptor stimulation is the primary mechanism underlaying
      the induction of these behaviours by SK&F 38393. However, the expression of
      certain individual responses to SK&F 38393 were sensitive to attenuation by the
      selective D(2) antagonists sulpiride or metoclopramide. These results extend the
      emerging view that the D(1) receptor is behaviourally relevant and that there
      exist functional interactions between D(1) and D(2) receptor systems in the
      regulation of behaviour.

PMID- 22158980
TI  - Effect of chlorimipramine and maprotiline on experimental anxiety in humans.
AB  - In order to assess the role played by serotonin (5-HT) and noradrenaline in
      anxiety, four groups of healthy volunteers were given 25 mg of the selective
      inhibitor of 5-HT uptake chlorimipramine, 50 mg of the selective inhibitor of
      noradrenaline uptake maprotiline, 1 mg of the benzodiazepine anxiolytic lorazepam
      or placebo, and submitted to a simulated public speaking (SPS) test, consisting
      of speaking in front of a videocamera. Subjective anxiety was evaluated by the
      visual analog mood scale (VAMS) of Norris as well as by the state-trait anxiety
      inventory (STAI) of Spielberger. Chlorimipramine enhanced SPS-induced anxiety,
      whereas maprotiline and lorazepam reduced anxiety during as well as outside the
      test period. Mental and physical sedation (VAMS) were increased by either
      maprotiline or lorazepam. In a scale of bodily symptoms, chlorimipramine tended
      to increase muscle tension, agitation and palpitation, whereas maprotiline caused
      lethargy. The rise in blood pressure induced by the SPS procedure outlasted the
      period of stress in the group treated with chlorimipramine. In contrast, the SPS
      induced increase in heart rate was enhanced by lorazepam. Chlor imipramine and
      maprotiline reduced salivation to the same extent. Pupillary diameter, however,
      was significantly increased by chlorimipramine alone. It may be tentatively sug
      gested that the proanxiogenic effect of chlorimipramine is related to changes in
      central 5-HT neurotransmission while the anxiolytic effect of maprotiline is
      associated with alteration of noradrenergic mechanisms. Increased peripheral
      sympathetic tone may also contribute to the proanxiety action of chlorimipramine.

PMID- 22158981
TI  - The comparative psychopathology of affective disorders in animals and humans.
AB  - Reviews of animal models of affective disorders commonly concentrate on the
      behavioural features thereof, the supposed neurochemical substrates, the mode of
      production and the response to treatment of the state in question but ignore
      questions of psycho pathology. An attempt is made to deal critically with the
      psychopathology of human and animal affective disorders in the light of current
      operational criteria for the diagnosis of major depressive disorders. It is
      argued thatthe psychopathological tradition stemming from Jaspers may be more
      appropriate to a consideration of animal models of affective disorders than the
      psychopathological positions implicit in psychoanalysis, behaviourism or current
      cognitive psychologies and in addition more suited to meet these criteria. The
      adoption of such a perspective results in a shift of emphasis from abnormalities
      of psychological content to demonstrable neuropsychological deficits and a
      definition of affective disorders, whether in animals or humans, as psychosomatic
      illnesses, possibly involving a pathology of circadian rhythmicity. This
      perspective also suggests that animal models may be useful in the devel opment of
      more refined diagnostic criteria for affective disorders in humans.

PMID- 22158982
TI  - Acetylcholinesterase activity in regions of rat brain following repeated
      administration of electroconvulsive shock.
AB  - It has previously been shown that 30 min after administration of a single elec
      troconvulsive shock (ECS) to rats there is a marked decrease in both soluble and
      total acetylcholinesterase (AChE) activity in the midbrain and hippocampus. In
      the current study it has been shown that AChE activity is unchanged in these
      regions (apart from a small rise in soluble AChE in the hippocampus) 30 min after
      the final ECS of a series of 10 (once daily for 10 days). Twenty-four hours after
      the last ECS there was a significant increase in total and membrane bound AChE
      activity in the striatum but not hippocampus, midbrain, cortex and amygdala. This
      change in the striatum may be associated with the change in GABA synthesis which
      has been shown to also occur in this region at the same time.

PMID- 22158983
TI  - Organic photoresponse materials and devices.
AB  - Organic photoresponse materials and devices are critically important to organic
      optoelectronics and energy crises. The activities of photoresponse in organic
      materials can be summarized in three effects, photoconductive, photovoltaic and
      optical memory effects. Correspondingly, devices based on the three effects can
      be divided into (i) photoconductive devices such as photodetectors,
      photoreceptors, photoswitches and phototransistors, (ii) photovoltaic devices
      such as organic solar cells, and (iii) optical data storage devices. It is
      expected that this systematic analysis of photoresponse materials and devices
      could be a guide for the better understanding of structure-property relationships
      of organic materials and provide key clues for the fabrication of high
      performance organic optoelectronic devices, the integration of them in circuits
      and the application of them in renewable green energy strategies (critical
      review, 452 references).

PMID- 22158984
TI  - Preferential elimination of thin single-walled carbon nanotubes by iron etching.
AB  - We report that iron particles-assisted etching can be applied to selectively
      remove single-walled carbon nanotubes (SWNTs) with diameters smaller than 1.2 nm
      via the catalytic hydrogenation of carbon in a film of SWNTs, which is proven by
      a Raman spectroscopy-based technique.

PMID- 22158985
TI  - Protein conformational dynamics in the mechanism of HIV-1 protease catalysis.
AB  - We have used chemical protein synthesis and advanced physical methods to probe
      dynamics-function correlations for the HIV-1 protease, an enzyme that has
      received considerable attention as a target for the treatment of AIDS. Chemical
      synthesis was used to prepare a series of unique analogues of the HIV-1 protease
      in which the flexibility of the "flap" structures (residues 37-61 in each monomer
      of the homodimeric protein molecule) was systematically varied. These analogue
      enzymes were further studied by X-ray crystallography, NMR relaxation, and pulse
      EPR methods, in conjunction with molecular dynamics simulations. We show that
      conformational isomerization in the flaps is correlated with structural
      reorganization of residues in the active site, and that it is preorganization of
      the active site that is a rate-limiting factor in catalysis.

PMID- 22158986
TI  - Niche specialization of terrestrial archaeal ammonia oxidizers.
AB  - Soil pH is a major determinant of microbial ecosystem processes and potentially a
      major driver of evolution, adaptation, and diversity of ammonia oxidizers, which
      control soil nitrification. Archaea are major components of soil microbial
      communities and contribute significantly to ammonia oxidation in some soils. To
      determine whether pH drives evolutionary adaptation and community structure of
      soil archaeal ammonia oxidizers, sequences of amoA, a key functional gene of
      ammonia oxidation, were examined in soils at global, regional, and local scales.
      Globally distributed database sequences clustered into 18 well-supported
      phylogenetic lineages that dominated specific soil pH ranges classified as acidic
      (pH <5), acido-neutral (5 <= pH <7), or alkalinophilic (pH >= 7). To determine
      whether patterns were reproduced at regional and local scales, amoA gene
      fragments were amplified from DNA extracted from 47 soils in the United Kingdom
      (pH 3.5-8.7), including a pH-gradient formed by seven soils at a single site (pH
      4.5-7.5). High-throughput sequencing and analysis of amoA gene fragments
      identified an additional, previously undiscovered phylogenetic lineage and
      revealed similar pH-associated distribution patterns at global, regional, and
      local scales, which were most evident for the five most abundant clusters.
      Archaeal amoA abundance and diversity increased with soil pH, which was the only
      physicochemical characteristic measured that significantly influenced community
      structure. These results suggest evolution based on specific adaptations to soil
      pH and niche specialization, resulting in a global distribution of archaeal
      lineages that have important consequences for soil ecosystem function and
      nitrogen cycling.

PMID- 22158987
TI  - Ralph M. Steinman: a man, a microscope, a cell, and so much more.

PMID- 22158990
TI  - Creation path of 35S from Fukushima not so obvious.

PMID- 22158989
TI  - Discovery of a phenotypic switch regulating sexual mating in the opportunistic
      fungal pathogen Candida tropicalis.
AB  - Sexual reproduction can promote genetic diversity in eukaryotes, and yet many
      pathogenic fungi have been labeled as obligate asexual species. It is becoming
      increasingly clear, however, that cryptic sexual programs may exist in some
      species, and that efficient mating requires the necessary developmental switch to
      be triggered. In this study we investigate Candida tropicalis, an important human
      fungal pathogen that has been reported to be asexual. Significantly, we
      demonstrate that C. tropicalis uses a phenotypic switch to regulate a cryptic
      program of sexual mating. Thus, diploid a and alpha cells must undergo a
      developmental transition to the mating-competent form, and only then does
      efficient cell-cell conjugation take place resulting in the formation of stable
      a/alpha tetraploids. We show that both the phenotypic switch and sexual mating
      depend on the conserved transcriptional regulator Wor1, which is regulated by
      temperature in other fungal species. In contrast, C. tropicalis mating occurs
      efficiently at both 25  degrees C and 37  degrees C, suggesting that it could
      occur in the mammalian host and have direct consequences for the outcome of an
      infection. Transcriptional profiling further reveals that ~ 400 genes are
      differentially expressed between the two phenotypic states, including the
      regulatory factor Wor1. Taken together, our results demonstrate that C.
      tropicalis has a unique sexual program, and that entry to this program is
      controlled via a Wor1-mediated, metastable switch. These observations have direct
      implications for the regulation and evolution of cryptic sexual programs in
      related fungal pathogens.

PMID- 22158991
TI  - Reversible alteration of calcium dynamics in cardiomyocytes during acute hypoxia
      transient in a microfluidic platform.
AB  - Heart disease is the leading cause of mortality in western countries. Apart from
      congenital and anatomical alterations, ischemia is the most common agent causing
      myocardial damage. During ischemia, a sudden decrease in oxygen concentration
      alters cardiomyocyte function and compromises cell survival. The calcium handling
      machinery, which regulates the main functional features of a cardiomyocyte, is
      heavily compromised during acute hypoxic events. Alterations in calcium dynamics
      have been linked to both short- and long-term consequences of ischemia, ranging
      from arrhythmias to heart failure. In this perspective, we aimed at investigating
      the calcium dynamics in functional cardiomyocytes during the early phase of a
      hypoxic event. For this purpose, we developed a microfluidic system specifically
      designed for controlling fast oxygen concentration dynamics through a gas micro
      exchanger allowing in line analysis of intracellular calcium concentration by
      confocal microscopy. Experimental results show that exposure of Fluo-4 loaded
      neonatal rat cardiomyocytes to hypoxic conditions induced changes in
      intracellular Ca(2+) transients. Such behavior was reversible and was detected
      for hypoxic levels below 5% of oxygen partial pressure. The observed changes in
      Ca(2+) dynamics were mimicked using specific L-type Ca(2+) channel antagonists,
      suggesting that alterations in calcium channel function occur at low oxygen
      levels. Reversible alteration in ion channel function, that takes place in
      response to changes in cellular oxygen, might represent an adaptive mechanism of
      cardiopreservation during ischemia.

PMID- 22158988
TI  - Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent
      mutations in components of ubiquitin-dependent pathways.
AB  - More than 2% of adults harbor a pancreatic cyst, a subset of which progresses to
      invasive lesions with lethal consequences. To assess the genomic landscapes of
      neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from
      the neoplastic epithelium of eight surgically resected cysts of each of the major
      neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous
      neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and solid pseudopapillary
      neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not
      SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs,
      and SPNs contained 10 +/- 4.6, 27 +/- 12, 16 +/- 7.6, and 2.9 +/- 2.1 somatic
      mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin
      ligase components were of particular note. Four of the eight SCAs contained
      mutations of the von Hippel-Lindau gene (VHL), a key component of the VHL
      ubiquitin ligase complex that has previously been associated with renal cell
      carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the
      eight MCNs harbored mutations of RNF43, a gene coding for a protein with
      intrinsic E3 ubiquitin ligase activity that has not previously been found to be
      genetically altered in any human cancer. The preponderance of inactivating
      mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and
      MCNs. SPNs contained remarkably few genetic alterations but always contained
      mutations of CTNNB1, previously demonstrated to inhibit degradation of the
      encoded protein (beta-catenin) by E3 ubiquitin ligases. These results highlight
      the essential role of ubiquitin ligases in these neoplasms and have important
      implications for the diagnosis and treatment of patients with cystic tumors.

PMID- 22158992
TI  - Antimonato polyoxovanadates with structure directing transition metal complexes:
      pseudopolymorphic {Ni(dien)2}3[V15Sb6O42(H2O)].nH2O compounds and
      {Ni(dien)2}4[V16Sb4O42(H2O)].
AB  - Three new poloxovanadates were synthesized under solvothermal conditions and were
      structurally characterized. The two compounds with composition
      {Ni(dien)(2)}(3)[V(15)Sb(6)O(42)(H(2)O)].nH(2)O (n = 12 and 8; dien = bis(2
      aminoethyl)amine or diethylenetriamine) are pseudopolymorphs crystallizing in
      different space groups. The compounds were obtained by applying identical
      reaction slurries but using different reaction temperatures. Both compounds
      feature the [V(15)Sb(6)O(42)(H(2)O)](6-) anion which is the antimony analogue to
      the single molecule magnet [V(15)As(6)O(42)(H(2)O)](6-). Crystal data: 1
      tetragonal space group P4, a = 46.9378(3), c = 16.51300(10) A and V = 36380.7(4)
      A(3). 2 rhombohedral space group R3c with a = 23.0517(4), c = 28.6216(5) A and V
      = 13171.3(4) A(3). In 1 several unusual short inter-cluster Sb...O contacts lead
      to the formation of three different super-clusters with composition
      V(60)Sb(24)O(168). The 12 unique {Ni(dien)(2)}(2+) complexes adopt all three
      possible configurations. In 2 the special arrangement of the {Ni(dien)(2)}(2+)
      complexes around the cluster anion prevents inter-cluster Sb...O contacts. The
      main structural motif of the third compound
      {Ni(dien)(2)}(4)[V(16)Sb(4)O(42)(H(2)O)] (3) is the [V(16)Sb(4)O(42)(H(2)O)](8-)
      cluster anion consisting of two perpendicular eight-membered rings of VO(5)
      pyramids. Two additional VO(5) polyhedra are located on opposite sides. Crystal
      data: 3 triclinic space group P1 = 13.5159(4), b = 14.2497(5), c = 14.9419(4) A,
      alpha = 98.322(2), beta = 114.080(2), gamma = 110.130(2) degrees  and V =
      2326.35(12) A(3).

PMID- 22158993
TI  - Maternal socio-economic indices for prenatal care research in rural China.
AB  - BACKGROUND: The conceptualization and measurement of socio-economic status (SES)
      is difficult in developing settings. In the absence of SES indices for women in
      rural China, we constructed SES indices for prenatal care research, and examined
      their relation to perinatal care and outcomes. METHODS: This study utilized data
      of 4364 rural women having recently given birth, collected by a cross-sectional
      survey in three rural Chinese provinces in 2007. Principal component analysis
      (PCA) was used to construct the SES indices and multilevel logistic regression
      was use to relate the indices to low birthweight, short exclusive breastfeeding
      (<=4 months), childbirth at the county or higher level health facility, caesarean
      section, inadequate prenatal care and no postnatal care. RESULTS: Three separate
      SES indices (wealth, occupational and educational indices) were obtained from the
      PCA analysis, capturing maternal, paternal and household SES characteristics.
      After adjusting for individual level factors, village and township wealth, higher
      levels of the indices were inversely associated with inadequate prenatal care.
      Higher occupational status was positively associated with short exclusive
      breastfeeding and childbirth at the county or higher level health facility, but
      inversely associated with no postnatal care. Higher educational status was
      positively associated with no postnatal care. CONCLUSION: Three SES indices
      (wealth, occupational and educational) were obtained from this study for prenatal
      care research. The indices gave mostly varying results on their associations with
      perinatal care and outcomes, indicating that SES measures may be outcome
      specific.

PMID- 22158994
TI  - Association between asthma and physical activity in Korean adolescents: the 3rd
      Korea Youth Risk Behavior Web-based Survey (KYRBWS-III).
AB  - BACKGROUND: Asthma is the leading chronic illness among children and adolescents
      in several nations. This study investigated the association between asthma and
      physical activity (PA). METHODS: The findings in this study are based on the data
      obtained from the 2007 3rd Korea Youth Risk Behavior Web-Based Survey (KYRBWS
      III), a cross-sectional survey of health-risk behaviours among a representative
      sample of Korean middle- and high-school students aged 13-18 years. This survey
      is conducted annually by the Korea Centers for Disease Control and Prevention.
      The 72 943 study subjects were selected using the complex sampling design of the
      survey. The association between asthma and PA was assessed by conducting multiple
      logistic regression analyses of the data by using the statistical software SPSS
      17.0 Complex Sample. RESULTS: Compared with the adolescents without current
      asthma, significantly fewer adolescents with current asthma had a sedentary time
      of 3 h or less per day (odds ratio, 0.86; 95% confidence interval, 0.75-0.97).
      Sedentary time was defined as time spent watching television, surfing the
      Internet, or playing computer games and excluded the time spent doing homework or
      study during leisure time. The analysis was adjusted for age, gender, family
      affluence level (FAL), obesity, allergic rhinitis, atopy and smoking. With regard
      to participation in adequate vigorous or moderate PA, strengthening exercise or
      physical education class, no significant differences were found between the
      adolescent students with current asthma and those without current asthma. In
      addition, it was found that all PA had no significant differences in their
      effects on asthma severity (medication, inability to work and absence from
      school). CONCLUSION: Our results show that the amount of sedentary time
      influenced asthma prevalence; however, PA did not influence asthma prevalence in
      Korean adolescents.

PMID- 22158996
TI  - Dutch digital breast cancer screening: implications for breast cancer care.
AB  - BACKGROUND: In comparison to other European population-based breast cancer
      screening programmes, the Dutch programme has a low referral rate, similar breast
      cancer detection and a high breast cancer mortality reduction. The referral rate
      in the Netherlands has increased over time and is expected to rise further,
      mainly following nationwide introduction of digital mammography, completed in
      2010. This study explores the consequences of the introduction of digital
      mammography on the balance between referral rate, detection of breast cancer,
      diagnostic work-up and associated costs. METHODS: Detailed information on
      diagnostic work-up (chart review) was obtained from referred women (n = 988) in
      2000-06 (100% analogue mammography) and 2007 (75% digital mammography) in
      Nijmegen, the Netherlands. RESULTS: The average referral rate increased from 15
      (2000-06) to 34 (2007) per 1000 women screened. The number of breast cancers
      detected increased from 5.5 to 7.8 per 1000 screens, whereas the positive
      predictive value fell from 37% to 23%. A sharp rise in diagnostic work-up
      procedures and total diagnostic costs was seen. On the other hand, costs of a
      single work-up slightly decreased, as less surgical biopsies were performed.
      CONCLUSION: Our study shows that a low referral rate in combination with the
      introduction of digital mammography affects the balance between referral rate and
      detection rate and can substantially influence breast cancer care and associated
      costs. Referral rates in the Netherlands are now more comparable to other
      countries. This effect is therefore of value in countries where implementation of
      digital breast cancer screening has just started or is still under discussion.

PMID- 22158995
TI  - Identification of recent HIV-1 infection among newly diagnosed cases in
      Catalonia, Spain (2006-08).
AB  - BACKGROUND: Quantification and description of patients recently infected by HIV
      can provide an accurate estimate of the dynamics of HIV transmission. Between
      2006 and 2008 in Catalonia, we estimated the prevalence of recent HIV infection
      among newly diagnosed cases, described the epidemiological characteristics of the
      infection according to whether it was recent, long-standing or advanced, and
      identified factors associated with recent infection. METHODS: A Test for Recent
      Infection (TRI) was performed in serum samples from patients newly diagnosed with
      HIV. Two different TRI were used: the Vironostika-LS assay (January 2006-May
      2007) and the BED-CEIA CEIA (June 2007 onwards). Samples were obtained within the
      first 6 months of diagnosis. Patients whose samples tested positive in the TRI
      were considered recently infected. RESULTS: Of 1125 newly diagnosed patients,
      79.9% were men (median age, 35.4 years), 38.7% were born outside Spain, 48.9%
      were men who have sex with men (MSM) and 10.6% presented other sexually
      transmitted infections. The overall percentage of recent infection was 23.0%,
      which increased significantly, from 18.1% in 2006 to 26.2% in 2008. This
      percentage was higher for patients from South America (27.6%). Factors associated
      with recent infection were acquiring infection through sexual contact between MSM
      [odds ratio (OR) 2.0; 95% confidence interval (95% CI) 1.1-3.9], compared with
      acquiring infection through heterosexual relations and being under 30 years of
      age (OR 5.9; 95% CI 1.9-17.4), compared with being over 50 years of age.
      CONCLUSION: The highest percentage of recent infection was identified in MSM,
      suggesting either a higher incidence or a greater frequency of HIV testing.
      Information regarding testing patterns is necessary to correctly interpret data
      from recently infected individuals. Systems to monitor the HIV epidemic should
      include both parameters.

PMID- 22158997
TI  - Pandemic influenza A (H1N1) 2009 in Madrid, Spain: incidence and characteristics
      in immigrant and native population.
AB  - BACKGROUND: Some immigrants and refugees might be more vulnerable than other
      groups to pandemic influenza because of pre-existing health and social
      disparities, migration history and living conditions. The objective of this study
      was to compare, between the immigrant and autochtonous population, the incidence
      and characteristics of influenza cases consulting in primary care (PC) and severe
      influenza cases. METHODS: Descriptive cross-sectional study of influenza episodes
      registered in PC and severe influenza cases reported between 1 May 2009 and 22
      May 2010, by gender and origin. Age-adjusted rates were calculated and the
      association between origin and chronic pathology, pregnancy, delay in admission
      to hospital and admission to intensive care units (ICU) was analyzed by logistic
      regression and generalized linear models. RESULTS: The influenza rate in PC,
      adjusted by age, was lower for immigrant population (2396.3, 95% confidence
      interval (95% CI) 2362.5-2430.0 vs. 2795.9, 95% CI 2780.4-2811.5 per 100, 000).
      The difference between severe influenza rates by origin was not statistically
      significant. Chronic conditions were less common in immigrant population. In
      severe influenza cases, pregnancy was more common in immigrant women, and the
      probability of admission to ICU was higher in men from Central and Eastern Europe
      (prevalence ratio (PR) 8.44, 95% CI 2.81-25.40) and North African women (PR 3.30,
      95% CI 1.09-10.05). CONCLUSION: Differences in influenza rates were detected by
      origin. This information could be useful for new pandemic wave management
      purposes, in addition to targetting future investigations. Pandemic influenza
      preparedness and response plans should incorporate specific actions to improve
      immigrants' access to health services and to decrease cultural barriers.

PMID- 22158998
TI  - Multifunctional dendritic polymers in nanomedicine: opportunities and challenges.
AB  - Nanotechnology has resulted in materials that have greatly improved the
      effectiveness of drug delivery because of their ability to control matter on the
      nanoscale. Advanced forms of nanomedicine have been synthesized for better
      pharmacokinetics to obtain higher efficacy, less systemic toxicity, and better
      targeting. These criteria have long been the goal in nanomedicine, in particular,
      for systemic applications in oncological disorders. Now, the "holy grail" in
      nanomedicine is to design and synthesize new advanced macromolecular nanocarriers
      and to translate them from lab to clinic. This review describes the current and
      future perspectives of nanomedicine with particular emphasis on the clinical
      targets in cancer and inflammation. The advanced forms of liposomes and
      polyethylene glycol (PEG) based nanocarriers, as well as dendritic polymer
      conjugates will be discussed with particular attention paid to designs, synthetic
      strategies, and chemical pathways. In this critical review, we also report on the
      current status and perspective of dendritic polymer nanoconjugate platforms (e.g.
      polyamidoamine dendrimers and dendritic polyglycerols) for cellular localization
      and targeting of specific tissues (192 references).

PMID- 22158999
TI  - The multiple dimensions of Integrative Biology.

PMID- 22159000
TI  - How Lewis acidic is your cation? Putting phosphenium ions on the fluoride ion
      affinity scale.
AB  - The fluoride ion affinities (FIAs) of 33 phosphenium ions with a range of
      substituents were calculated using ab inito and DFT methods. The use of these FIA
      data as a measure of the Lewis acidities of phosphenium ions is described and the
      FIAs of the species studied here are compared to FIA data for more commonly
      encountered Lewis acids. Phosphenium ions are often stronger Lewis acids than
      neutral species, but in many cases are less Lewis acidic than highly
      electrophilic cations such as [Me(3)C](+) or [Me(3)Si](+). The impact of
      mesomeric, inductive and steric substituent effects on FIAs are discussed and
      related to the underlying electronic structures of different cation types. A
      comparison between the FIAs of known "free" phosphenium ions with those that are
      currently unknown and other highly electrophilic cations suggests that some
      diaryl- and dialkylphosphenium ions may yet be accessible under the right
      conditions.

PMID- 22159001
TI  - Coordination of copper(II) ions by the fragments of neuropeptide gamma containing
      D1, H9, H12 residues and products of copper-catalyzed oxidation.
AB  - A potentiometric, spectroscopic (UV-Vis, CD and EPR) and mass spectrometric (ESI
      MS) study of Cu(II) binding to the (1-2,7-21)NPG, Asp(1)-Ala-Ile(7)-Ser-His(9)
      Lys-Arg-His(12)-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met(21)-NH(2), and Ac-(1-2,7
      21)NPG, Ac-Asp(1)-Ala-Ile(7)-Ser-His(9)-Lys-Arg-His(12)-Lys-Thr-Asp-Ser-Phe-Val
      Gly-Leu-Met(21)-NH(2), fragments of neuropeptide gamma were carried out. The
      results clearly indicate the stabilization of the 1 N {NH(2), beta-COO(-)}, 2 N
      {NH(2), beta-COO(-), N(Im)} and 3 N {NH(2), beta-COO(-), 2N(Im)} complexes by the
      coordination of the beta-carboxylate group of the D(1) residue. For the (1-2,7
      21)NPG the CuH(2)L complex with 3 N {NH(2), beta-COO(-), 2N(Im)}, the binding
      mode dominates in a wide pH range of 4-8.5. With the sequential increase of pH,
      deprotonated amide nitrogens are involved in copper coordination. For the Ac-(1
      2,7-21)NPG peptide the imidazole nitrogen atoms are the primary metal binding
      sites forming macrochelates in the pH range 4 to 7. The CuHL complex with 4 N
      {N(Im), N(-), N(-), N(Im)} coordination mode is formed in pH range 6-9.
      Deprotonation and co-ordination of the third amide nitrogen were detected at pH
      ~8.6. Metal-catalyzed oxidation (MCO) of proteins is mainly a site-specific
      process in which one or a few amino acids at metal-binding sites on the protein
      are preferentially oxidized. To elucidate the products of the copper(II)
      catalyzed oxidation of the (1-2,7-21)NPG and Ac-(1-2,7-21)NPG, the liquid
      chromatography-mass spectrometry (LC-MS) method and Cu(II)/hydrogen peroxide as a
      model oxidizing system were employed. In the presence of hydrogen peroxide with 1
      : 4 peptide-H(2)O(2) molar ratio for the Ac-(1-2,7-21)NPG peptide the oxidation
      of the methionine residue to methionine sulfoxide and for (1-2,7-21)NPG to
      sulfone was observed. For the Cu(II)-peptide-hydrogen peroxide in 1 : 1 : 4 molar
      ratio systems, oxidation of the histidine residues to 2-oxohistidines was
      detected. Under experimental conditions the (1-2,7-21)NPG and Ac-(1-2,7-21)NPG
      undergo fragmentations by cleavage of the S(8)-H(9), H(9)-K(10), R(11)-H(12) and
      H(12)-K(13) peptide bonds supporting the participation of the H(9) and H(12)
      residues in the coordination of copper(II) ions. For the (1-2,7-21)NPG peptide
      chain the involvement of the D(1) residue in the coordination of metal ions is
      supported by the alkoxyl radical modification of this amino acid residue.

PMID- 22159002
TI  - Changes in COPD mortality rate after amendments to the Preventive Vaccination Law
      in Japan.
AB  - BACKGROUND: The Japanese government amended the Preventive Vaccination Law in
      November 2001 to specify elderly people aged >= 65 years as the target population
      for influenza vaccinations. The vaccine coverage among this age group rapidly
      increased thereafter. Our goal was to evaluate how this amendment affected the
      nationwide mortality rate of chronic obstructive pulmonary disease (COPD).
      METHODS: The number of monthly COPD deaths by gender and age was obtained from
      the Monthly Vital Statistics Reports of the Ministry of Health, Labour and
      Welfare. Data between January 1995 and December 2009 were used for analyses. The
      COPD mortality rate for each month was calculated separately for the two age
      groups: age <65 years and age >= 65 years. Changes in the COPD mortality rates
      after amendment were evaluated each month using the Poisson regression analysis
      to calculate risk ratios (RRs) and to compute 95% confidence intervals (95% CIs)
      adjusting for gender, age, trend and seasonal variations. RESULTS: After
      amendments to the law, a statistically significant reduction in the COPD
      mortality rates were observed in January (RR 0.84; 95% CI 0.81-0.88), February
      (RR 0.85; 95% CI 0.81-0.89) and March (RR 0.92; 95% CI 0.88-0.96) among the
      population aged >= 65 years. However, in the population aged <65 years,
      statistically no significant changes in the COPD mortality rate were found in any
      month after the amendments were made. CONCLUSION: A legal approach to improving
      influenza vaccine coverage for the elderly population would contribute to the
      risk reduction of COPD deaths during the influenza season.

PMID- 22159004
TI  - The source of moving particles in parafoveal capillaries detected by adaptive
      optics scanning laser ophthalmoscopy.
AB  - PURPOSE: To investigate the source of moving particles in parafoveal capillaries
      detected by adaptive optics scanning laser ophthalmoscopy (AO-SLO). METHODS: AO
      SLO videos were acquired from the parafoveal areas of eyes of healthy subjects.
      The gray-scale values inside and outside the moving particles were measured and
      compared. Thereafter, successive frames of the captured videos were analyzed
      under higher magnification to detect changes in the gray values of bright spots
      inside the capillaries, before and during passage of the particles.
      Simultaneously, changes in the gray values of areas without the bright spots were
      measured for comparison. Then, the authors analyzed the packing arrangements of
      the bright spots in the particles, and measured the particle velocity using
      spatiotemporal images of the target capillary. RESULTS: There were no significant
      differences in the gray values between the moving particles and the cone mosaic
      outside the parafoveal capillaries adjacent to the particles. The gray value of
      the bright spots in the dark shadow of the vessels increased when the particles
      passed through, while the dark areas without bright spots remained dark. There
      were no significant differences in the packing arrangements between the bright
      spots and surrounding cone mosaic. Further, the concordance rate of packing
      arrangements of bright spots between two consecutive moving particles in the
      capillary was 95.8%. The mean particle velocity was 1.34 +/- 0.42 mm/s.
      CONCLUSIONS: The particles moving in the capillaries are suggested to be
      reflections of photoreceptor aggregates that pass through circulating transparent
      objects such as leukocytes or plasma gaps.

PMID- 22159003
TI  - Spectral-domain optical coherence tomography enhanced depth imaging of the normal
      and glaucomatous nonhuman primate optic nerve head.
AB  - PURPOSE: To test whether the enhanced depth imaging (EDI) modality improves
      anterior and posterior lamina cribrosa surface (ALCS and PLCS) visibility
      compared with conventional spectral-domain optical coherence tomography (SD-OCT).
      METHODS: Conventional and EDI SD-OCT scans were obtained 30 minutes after IOP was
      manometrically lowered to 10 mm Hg in both eyes of 14 nonhuman primates (NHPs)
      with unilateral experimental glaucoma (EG). Thirteen horizontal and seven
      vertical radial B-scans of each SD-OCT data set were delineated by one operator
      masked to image type. Delineated ALCS and PLCS points were projected to 1 of 100
      equal-sized subregions of the neural canal opening (NCO) reference plane, and the
      number of delineated subregions (>=2 points) was counted. Poisson regression was
      used to analyze the effects of image type, treatment, and quadrant. Two
      additional delineations were performed for three NHPs to compare reproducibility.
      RESULTS: EDI increased the number of subregions delineated for both the ALCS (by
      28%; P < 0.0001) and PLCS (by 225%; P < 0.0001). EDI improvement in ALCS
      visibility was significant in the superior quadrant only and was not different in
      EG versus control eyes, whereas EDI improvement in PLCS visibility was
      significant in all four quadrants (P < 0.005) and greater in EG eyes (P < 0.001),
      nasally and temporally. Intradelineator reproducibility was not different between
      image types. EDI and standard ONH parameter values were similar except for PLCS
      depth which was deeper in the EDI data sets (P = 0.0002). CONCLUSIONS: ALCS and
      PLCS visibility within control and EG NHP ONHs increased in EDI compared to
      conventional SD-OCT data sets. Further study of EDI effects on PLCS
      parameterization is required.

PMID- 22159005
TI  - Pseudomonas aeruginosa keratitis: outcomes and response to corticosteroid
      treatment.
AB  - PURPOSE: To compare the clinical course and effect of adjunctive corticosteroid
      therapy in Pseudomonas aeruginosa with those of all other strains of bacterial
      keratitis. METHODS: Subanalyses were performed on data collected in the Steroids
      for Corneal Ulcers Trial (SCUT), a large randomized controlled trial in which
      patients were treated with moxifloxacin and were randomly assigned to 1 of 2
      adjunctive treatment arms: corticosteroid or placebo (4 times a day with
      subsequent reduction). Multivariate analysis was used to determine the effect of
      predictors, organism, and treatment on outcomes, 3-month best-spectacle-corrected
      visual acuity (BSCVA), and infiltrate/scar size. The incidence of adverse events
      over a 3-month follow-up period was compared using Fisher's exact test. RESULTS:
      SCUT enrolled 500 patients. One hundred ten patients had P. aeruginosa ulcers; 99
      of 110 (90%) enrolled patients returned for follow-up at 3 months. Patients with
      P. aeruginosa ulcers had significantly worse visual acuities than patients with
      other bacterial ulcers (P = 0.001) but showed significantly more improvement in 3
      month BSCVA than those with other bacterial ulcers, adjusting for baseline
      characteristics (-0.14 logMAR; 95% confidence interval, -0.23 to -0.04; P =
      0.004). There was no significant difference in adverse events between P.
      aeruginosa and other bacterial ulcers. There were no significant differences in
      BSCVA (P = 0.69), infiltrate/scar size (P = 0.17), and incidence of adverse
      events between patients with P. aeruginosa ulcers treated with adjunctive
      corticosteroids and patients given placebo. CONCLUSIONS: Although P. aeruginosa
      corneal ulcers have a more severe presentation, they appear to respond better to
      treatment than other bacterial ulcers. The authors did not find a significant
      benefit with corticosteroid treatment, but they also did not find any increase in
      adverse events. (ClinicalTrials.gov number, NCT00324168.).

PMID- 22159006
TI  - Profiling retinal biochemistry in the MPDZ mutant retinal dysplasia and
      degeneration chick: a model of human RP and LCA.
AB  - PURPOSE: Raman microscopy, a rapid nondestructive technique that profiles the
      composition of biological samples, was used to characterize retinal biochemistry
      in the retinal dysplasia and degeneration (rdd) and wild-type (wt) chick retina
      during retinogenesis and at hatching. METHODS: Embryonic day (E)13 and posthatch
      day (P)1 rdd and wt retinal cross-sections (n = 3 of each line at each age) were
      profiled using 633 helium-neon laser excitation. The biochemical composition was
      determined using computational analysis of the Raman spectra. In parallel
      histology, TUNEL and glial fibrillary acidic protein (GFAP) immunostaining were
      used to visualize retinal dysfunction. RESULTS: Principal component (PC) analysis
      of the Raman spectra identified 50 major biochemical profiles, but only PCs that
      made significant contributions to variation within rdd and wt retina were mapped.
      These significant PCs were shown to arise from DNA, various fatty acids, melanin,
      and a number of proteins. Distinct patterns of GFAP immunostaining and a larger
      population of TUNEL-positive nuclei were observed in the rdd versus wt retina.
      CONCLUSIONS: This study has demonstrated that Raman microscopy can discriminate
      between major retinal biomolecules, thus providing an unbiased account of how
      their composition varies due to the impact of the MPDZ null mutation in the rdd
      chick relative to expression in the normal wt retina.

PMID- 22159007
TI  - Correlation of fundus autofluorescence gray values with vision and microperimetry
      in resolved central serous chorioretinopathy.
AB  - PURPOSE: To evaluate the prognostic value of grayscale parameters in fundus
      autofluorescence (FAF) for visual function in resolved central serous
      chorioretinopathy (CSC). METHODS: Seventy-six eyes of 67 patients with CSC that
      had been resolved for more than 4 months were analyzed retrospectively. Both the
      short-wavelength (SW)-FAF and near infrared (NIR)-FAF gray value parameters,
      including the mean, standard deviation, and coefficient of variation (CV), were
      calculated at 350-MUm- and 1200-MUm-diameter circles centered on the fovea. The
      FAF gray value parameters correlated with -logMAR best corrected visual acuity
      (BCVA) and mean microperimetry (MP) at the 2 degrees  and 4 degrees  diameters
      from the foveal center. RESULTS: The mean -logMAR BCVA was 0.15 +/- 0.23. The
      mean MP was 12.87 +/- 3.79 dB at 2 degrees  and 13.54 +/- 3.37 dB at 4 degrees .
      The -logMAR BCVA correlated most strongly with the mean SW-FAF gray value at the
      350-MUm circle centered around the fovea (SW-M350; rho = 0.353; P = 0.002), and
      the SD of the SW-FAF gray value at the 350-MUm circle centered around the fovea
      (SW-SD350) correlated most strongly with the MP at 2 degrees  (rho = -0.416, P <
      0.0001) and 4 degrees  (rho = -0.435, P < 0.0001). The NIR-FAF gray value
      parameters did not correlate with the macular function tests. CONCLUSIONS: In
      subjects with resolved CSC, FAF gray values correlated with visual function. BCVA
      correlated most strongly with SW-M350. MP at 2 degrees  and at 4 degrees 
      correlated most strongly with SW-SD350.

PMID- 22159008
TI  - Heritability of peripheral refraction in Chinese children and adolescents: the
      Guangzhou Twin Eye study.
AB  - PURPOSE: To estimate the heritability of peripheral refraction in Chinese
      children and adolescents. METHODS: The authors examined 72 monozygotic (MZ) twins
      and 48 dizygotic (DZ) twins aged 8 to 20 years from a population-based twin
      registry. Temporal and nasal peripheral refraction, each 40 degrees  from the
      visual axis, and axial refraction were measured using an autorefractor. Relative
      peripheral refractive error (RPRE) was defined as the peripheral refraction minus
      the axial refraction. Heritability was assessed by structural equation modeling
      after adjustment for age and sex. RESULTS: The mean and SD of temporal refraction
      (T(40)), nasal refraction (N(40)), RPRE-T(40), RPRE-N(40), and T(40)-N(40)
      asymmetry were -0.27 +/- 2.0 D, 0.36 +/- 2.19 D, 1.18 +/- 1.39 D, 1.80 +/- 1.69
      D, and -0.62 +/- 1.58 D, respectively. The intraclass correlations for T(40)
      refraction, N(40) refraction, RPRE-T(40), RPRE-N(40), and T(40)-N(40) asymmetry
      were 0.87, 0.83, 0.65, 0.74, and 0.58 for MZ pairs and 0.49, 0.42, 0.30, 0.41,
      and 0.32 for DZ pairs, respectively. A model with additive genetic and unique
      environmental effects was the most parsimonious, with heritability values
      estimated as 0.84, 0.76, 0.63, 0.70, and 0.55, respectively, for the peripheral
      refractive parameters. CONCLUSIONS: Additive genetic effects appear to explain
      most of the variance in peripheral refraction and relative peripheral refraction
      when adjusting for the effects of axial refraction.

PMID- 22159009
TI  - Novel noninvasive detection of the fovea avascular zone using confocal red-free
      imaging in diabetic retinopathy and retinal vein occlusion.
AB  - PURPOSE: To report confocal red-free imaging as a novel, noninvasive imaging
      modality for the detection of the foveal avascular zone (FAZ) and to compare its
      effectiveness to that of fluorescein angiography (FA) in diabetic retinopathy
      (DR) and retinal vein occlusion (RVO). METHODS: This was a retrospective,
      observational, cross-sectional study. The authors enrolled 50 eyes with DR and 20
      eyes with RVO. All subjects underwent confocal red-free imaging and FA using a
      scanning laser ophthalmoscope. For all subjects, the FAZ was identified on both
      confocal red-free and corresponding FA images and was delineated by two
      independent readers. The authors evaluated the concordance between the two
      imaging methods by comparing the sizes of the delineated areas and determining
      the overlapping ratio after image processing. RESULTS: The image analysis showed
      a high correlation (r > 0.9) in the mean size of the FAZ between the red-free and
      corresponding FA images with DR or RVO. Reliable agreement between the two
      methods was confirmed by the comparison of size (P = 0.925 on independent t-test)
      and overlapping correspondence (overlapping ratio, 0.77) of the delineated area.
      CONCLUSIONS: The findings suggest that confocal red-free imaging is a simple,
      reliable, safe, and noninvasive method for effectively imaging the FAZ. This
      procedure has the potential to be used for the noninvasive detection and
      quantification of FAZ in screening, initial evaluation, and follow-up observation
      of progressive ischemic retinopathies such as DR and RVO.

PMID- 22159010
TI  - Effects of aging on 24-hour intraocular pressure measurements in sitting and
      supine body positions.
AB  - PURPOSE: To evaluate how aging alters 24-hour measurements of intraocular
      pressure (IOP) in the sitting and supine body positions. METHODS: Fifteen older
      volunteers with healthy eyes (ages, 53-71 years) were each housed for 1 day in a
      sleep laboratory. An 8-hour accustomed sleep period was assigned to each subject.
      Every 2 hours, measurements of IOP were taken in the sitting and supine
      positions. Sitting and supine patterns of 24-hour IOP were compared. Simulated 24
      hour IOP rhythms in the same body position were determined using cosine fitting
      of individual 24-hour data. The average postural IOP effects during the
      diurnal/wake period and the nocturnal/sleep period were compared. Data from this
      group of older subjects were compared with previously collected data from 16
      healthy younger subjects (ages, 18-25 years) under the same experimental
      conditions. RESULTS: Within each age group, sitting and supine patterns of 24
      hour IOP were similar and parallel. Compared to the younger subjects, the phase
      timing (simulated peak) of 24-hour IOP was significantly delayed for the older
      subjects in both body positions. The postural IOP effect for the older subjects
      was 4.7 +/- 0.8 and 4.8 +/- 0.8 mm Hg during the diurnal and nocturnal periods,
      respectively. These postural IOP effects were not significantly different from
      the postural effects in the younger subjects. CONCLUSIONS: Although aging can
      significantly delay the phase timing of the 24-hour IOP pattern toward the
      diurnal/awake period, it may not affect the postural IOP effect during the
      diurnal and the nocturnal periods.

PMID- 22159011
TI  - Multifocal pupillography identifies ranibizumab-induced changes in retinal
      function for exudative age-related macular degeneration.
AB  - PURPOSE: To investigate the efficacy of multifocal pupillographic objective
      perimetry (mfPOP) to quantify the effects of intravitreal ranibizumab injection
      for choroidal neovascularization (CNV) secondary to exudative age-related macular
      degeneration (AMD). METHODS: mfPOP visual fields from 20 patients with unilateral
      exudative AMD treated with intravitreal ranibizumab were measured before and
      after 3 months of treatment and were compared with that in 30 normal subjects.
      Two stimulus types consisting of ensembles of 24 or 44 independent stimuli per
      eye had a mean presentation interval at each region of 1 second. Pupil responses
      were recorded with video cameras under infrared illumination. Multiple linear
      models were fitted to contraction amplitudes and delay to peak responses, to
      determine the independent effects of exudative AMD before and after ranibizumab
      therapy. RESULTS: After 3 months of treatment, mean additional response delays
      compared to normal subjects for the 24-region stimulus improved significantly (P
      < 5 * 10-9) from a mean of 18.82 +/- 3.0 ms at baseline to 7.45 +/- 3.15 ms. The
      mean effect of exudative AMD at baseline decreased constriction amplitude by 
      1.11 +/- 0.24 dB (P < 0.00001) with little improvement after ranibizumab therapy.
      Small pretreatment elevations of extrafoveal sensitivity correlated with
      improvements in central retinal thickness (CRT) after treatment (P < 0.0005).
      CONCLUSIONS: Improvements in mfPOP contraction amplitudes and time to peak
      responses were measured in eyes treated with intravitreal ranibizumab; however,
      response delays appeared to be the most indicative of functional improvement.
      Confirmation of hypersensitivity in the extrafoveal field in a larger group may
      support this finding as a prognostic marker for good treatment outcomes.

PMID- 22159012
TI  - Brillouin optical microscopy for corneal biomechanics.
AB  - PURPOSE: The mechanical properties of corneal tissue are linked to prevalent
      ocular diseases and therapeutic procedures. Brillouin microscopy is a novel
      optical technology that enables three-dimensional mechanical imaging. In this
      study, the feasibility of this noncontact technique was tested for in situ
      quantitative assessment of the biomechanical properties of the cornea. METHODS:
      Brillouin light-scattering involves a spectral shift proportional to the
      longitudinal modulus of elasticity of the tissue. A 532-nm single-frequency laser
      and a custom-developed ultrahigh-resolution spectrometer were used to measure the
      Brillouin frequency. Confocal scanning was used to perform Brillouin elasticity
      imaging of the corneas of whole bovine eyes. The longitudinal modulus of the
      bovine corneas was compared before and after riboflavin corneal collagen photo
      cross-linking. The Brillouin measurements were then compared with conventional
      stress-strain mechanical test results. RESULTS: High-resolution Brillouin images
      of the cornea were obtained, revealing a striking depth-dependent variation of
      the elastic modulus across the cornea. Along the central axis, the Brillouin
      frequency shift varied gradually from 8.2 GHz in the epithelium to 7.5 GHz near
      the endothelium. The coefficients of the down slope were measured to be
      approximately 1.09, 0.32, and 2.94 GHz/mm in the anterior, posterior, and
      innermost stroma, respectively. On riboflavin collagen cross-linking, marked
      changes in the axial Brillouin profiles (P < 0.001) were noted before and after
      cross-linking. CONCLUSIONS: Brillouin imaging can assess the biomechanical
      properties of cornea in situ with high spatial resolution. This novel technique
      has the potential for use in clinical diagnostics and treatment monitoring.

PMID- 22159013
TI  - The vitreous glycoprotein opticin inhibits preretinal neovascularization.
AB  - PURPOSE: Opticin is an extracellular matrix glycoprotein that the authors
      discovered in the vitreous humor of the eye. It is synthesized by the
      nonpigmented ciliary epithelium and secreted into the vitreous cavity and,
      unusually for an extracellular matrix molecule, high-level synthesis is
      maintained into adult life. Here the authors investigated the hypothesis that
      opticin influences vascular development in the posterior segment of the eye and
      pathologic angiogenesis into the normally avascular, mature (secondary) vitreous.
      METHODS: Opticin was localized in murine eyes by immunohistochemistry. An opticin
      knockout mouse was established and vascular development was compared between
      knockout and wild-type mice. Wild-type and opticin null mice were compared in the
      oxygen-induced retinopathy model, a model of pathologic angiogenesis, and this
      model was also used to assess the effects of intravitreal injection of
      recombinant opticin into eyes of wild-type mice. RESULTS: Opticin colocalizes
      with the collagen type II-rich fibrillar network of the vitreous, the inner
      limiting lamina, the lens capsule, the trabecular meshwork, and the iris.
      Analyses of the hyaloid and retinal vasculature showed that opticin has no effect
      on hyaloid vascular regression or developmental retinal vascularization. However,
      using the oxygen-induced retinopathy model, the authors demonstrated that opticin
      knockout mice produce significantly more preretinal neovascularization than wild
      type mice, and the intravitreal delivery of excess opticin inhibited the
      formation of neovessels in wild-type mice. CONCLUSIONS: A lack of opticin does
      not influence vascular development, but opticin is antiangiogenic and inhibits
      preretinal neovascularization.

PMID- 22159014
TI  - Lysosomal phospholipase A2 activity in pig aqueous humor.
AB  - PURPOSE: The present study was conducted to determine lysosomal phospholipase A2
      (LPLA2) activity in the aqueous humor (AH) and to identify the possible sources
      of the LPLA2 found in the AH. METHODS: To detect LPLA2 activity in pig AH and
      ocular tissues, liposomes consisting of 1,2-dioleoylphosphatidylglycerol/N
      acetylsphingosine were used as substrates in an activity assay under acidic
      conditions. The reaction products were separated by thin-layer chromatography. To
      identify the LPLA2 in pig AH, the AH was analyzed by Western immunoblot analysis
      with an anti-LPLA2 antibody. Distribution of the LPLA2 in pig ocular tissues was
      studied by determining its activity in individual tissue extracts. RESULTS: LPLA2
      activity was detected in the AH obtained from pig eyes. Consistent with the known
      properties of LPLA2, the activity was heat-labile and undetectable at neutral pH.
      The immunoblot of pig AH showed the anti-LPLA2 antibody-reactive protein band. In
      addition, the specific activity of the enzyme, when normalized to volume, was
      higher in pig AH than in pig serum. Individual tissue extracts obtained from pig
      ocular tissues showed different specific activity of LPLA2. In particular, the
      extract prepared from the trabecular meshwork provided the highest specific
      activity. CONCLUSIONS: The present findings suggest that the phospholipase A2
      activity found in pig AH under acidic conditions is due to LPLA2 and that it
      originates from ocular tissues surrounding the anterior chamber as well as
      plasma.

PMID- 22159015
TI  - The rate of visual field change in the ocular hypertension treatment study.
AB  - PURPOSE: To assess the rate of change of visual field (VF) mean deviation (MD) in
      the Ocular Hypertension Treatment Study (OHTS). METHODS: OHTS data were filtered
      to exclude eyes that had fewer than 10 reliable VFs or less than 5 years of
      follow-up or that reached a nonglaucomatous endpoint. The rate of change of MD
      (MDR) was calculated for each eye. Differences were sought between groups of eyes
      differing in primary open angle glaucoma (POAG) outcome, how POAG was determined,
      and original randomization. RESULTS: In total, 2609 eyes (1379 participants) met
      the selection criteria. The mean MDR was -0.08 +/- 0.20 dB/y (+/-SD). POAG eyes
      (n = 359) had significantly worse MDRs (-0.26 +/- 0.36 dB/y) than non-POAG eyes
      (n = 2250; -0.05 +/- 0.14 dB/y; P < 0.001). Eyes that reached POAG endpoints
      based on only VF change (n = 74; -0.29 +/- 0.31 dB/y) or only optic disc change
      (n = 158; -0.12 +/- 0.19 dB/y) had significantly worse MDRs than non-POAG eyes
      (both P < 0.001). Eyes that reached POAG endpoints for both VF and optic disc
      change (n = 127) deteriorated more rapidly (-0.42 +/- 0.46 dB/y) than eyes
      showing only VF change (P = 0.017) or only optic disc change (P < 0.001). There
      was not a significant association between MDR and original OHTS randomization
      (observe vs. treat, P = 0.168). CONCLUSIONS: Eyes that develop POAG have
      significantly worse MDRs than eyes that do not. Eyes that reached endpoints due
      to both VF and optic disc change had worse MDRs than eyes displaying change in
      only one of these. MDR was not significantly associated with randomization,
      suggesting that MDR may not be the best measure of VF change in early-stage POAG.
      (ClinicalTrials.gov number, NCT00000125.).

PMID- 22159016
TI  - Interocular symmetry of abnormal multifocal electroretinograms in adolescents
      with diabetes and no retinopathy.
AB  - PURPOSE: To investigate, in adolescents with type 1 diabetes and no retinopathy,
      the spatial correspondence between abnormal multifocal electroretinogram (mfERG)
      responses in the two eyes. METHODS: mfERG and fundus photographs were measured in
      both eyes of 68 adolescents with type 1 diabetes and no retinopathy (13 to 19
      years old; best corrected visual acuity >= 20/20), and 30 age-matched controls.
      The mfERG stimulus was comprised of 103 hexagons, and subtended 45 degrees .
      mfERG implicit times (IT) and amplitudes (AMP) were derived. Fifteen patients for
      IT, and five for AMP with at least one eye defined as abnormal (six or more
      locations with abnormal Z-scores; P < 0.03) were analyzed. RESULTS: Nasal retina
      had significantly more abnormal IT locations compared with temporal retina (P =
      0.015), and the opposite was true with regard to abnormal AMP (P < 0.001). The
      proportion of abnormal responses in the superior retina was not significantly
      different from that in the inferior retina (P > 0.1 for IT and AMP). Interocular
      correspondence of locations with abnormal mfERG IT was significant for all 15
      patients (P values <0.0001-0.012), and agreement between eyes was 68% to 94% (AC1
      agreement coefficient: 0.48-0.94). Overall interocular correspondence was also
      significant (P < 0.0002), with 86% agreement (AC1 = 0.76). Overall interocular
      correspondence of locations with abnormal mfERG AMP was also significant (P <
      0.0002). CONCLUSIONS: Interocular spatial correspondence of abnormal mfERG
      responses exists in adolescents with type 1 diabetes and no retinopathy. This is
      most apparent for IT abnormalities. This correspondence could be used in clinical
      trials, and raises the possibility of initiating treatment in both eyes at early
      disease stages as new topical treatments emerge.

PMID- 22159017
TI  - Diagnostic characteristics of tests for ocular Chlamydia after mass azithromycin
      distributions.
AB  - PURPOSE: Although trachoma control programs frequently use the World Health
      Organization (WHO) simplified grading system for trachoma to monitor the clinical
      response after repeated mass azithromycin treatments, the programmatic relevance
      of this evaluation after multiple rounds of antibiotic treatments is unclear.
      METHODS: Three rounds of annual mass azithromycin were distributed to 12 villages
      in Ethiopia. Twelve months after the third treatment, children were assessed for
      follicular trachomatous inflammation (TF) and intense trachomatous inflammation
      (TI) using the WHO simplified grading system and for ocular chlamydial infection
      using DNA-based and RNA-based tests. Test characteristics for predicting
      chlamydial infection were computed assuming a chlamydial RNA-based gold standard.
      As a secondary analysis, test characteristics were also assessed using a latent
      class analysis. RESULTS: The prevalence of RNA evidence of ocular chlamydia was
      7.1% (95% confidence interval [CI], 2.7-17.4). A DNA-based test and TF had
      sensitivities of 61.0% (95% CI, 47.1-73.3) and 65.9% (95% CI, 41.6-83.9),
      specificities of 100% (95% CI, 99.3-100) and 67.5% (95% CI, 61.0-73.5), and
      positive predictive values of 100% (95% CI, 86.3-100) and 13.4% (95% CI, 5.5
      29.3) compared with an RNA-based gold standard. The latent class analysis
      confirmed that the RNA-based test was a reasonable choice for a gold standard,
      with a sensitivity of 100% (95% CI, 67.1-100) and specificity of 99.6% (95% CI,
      98.1-100). CONCLUSIONS: Basing treatment decisions after mass azithromycin
      distributions on the WHO simplified grading system will maximize the treatment of
      infected persons compared with a DNA-based test but will also result in more
      uninfected persons being treated. The RNA-based test was considerably more
      sensitive, and almost equivalently specific, compared with a DNA-based test.
      (ClinicalTrials.gov number, NCT00322972.).

PMID- 22159018
TI  - Multiplex cytokine analysis of aqueous humor in eyes with primary open-angle
      glaucoma, exfoliation glaucoma, and cataract.
AB  - PURPOSE: To measure levels of various inflammatory cytokines in the aqueous humor
      of patients with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG),
      and senile cataract. METHODS: Aqueous humor samples were obtained from 64 eyes of
      64 Japanese subjects (POAG, 20 eyes; EXG, 23 eyes; and cataract, 21 control
      eyes). The levels of eight cytokines including interleukin (IL)1-beta, IL-6, IL
      8, transforming growth factor (TGF)-beta1, tumor necrosis factor (TNF)-alpha,
      serum amyloid A (SAA), migration inhibitory factor (MIF), and vascular
      endothelial growth factor (VEGF)-A were estimated using the multiplex bead
      immunoassay technique. RESULTS: Compared with the cataract group, the levels of
      TGF-beta1, IL-8, and SAA were significantly higher in aqueous humor samples from
      the POAG (5.0-fold, 2.3-fold, and 11.9-fold, respectively) and EXG (12.5-fold,
      4.0-fold, and 18.3-fold, respectively) groups. Except for a significant decrease
      in the IL-6 level in the POAG (0.23-fold) group, no other cytokine levels
      differed in the POAG and EXG groups compared with the cataract group. The levels
      of TGF-beta1, IL-8, and SAA were positively correlated with each other (rho =
      0.723-0.786; P < 0.0001), the intraocular pressure (IOP) (rho = 0.392-0.662; P <
      0.0001-0.0019), and the number of glaucoma medications (rho = 0.478-0.659; P <
      0.0001-0.0001). CONCLUSIONS: Cytokine networks including TGF-beta1, IL-8, and SAA
      in aqueous humor may have critical roles in IOP elevations in patients with open
      angle glaucoma.

PMID- 22159019
TI  - Automated characterization of pigment epithelial detachment by optical coherence
      tomography.
AB  - PURPOSE: To assess the accuracy of automated classification of pigment epithelial
      detachments (PED) by using a software algorithm applied to spectral-domain
      optical coherence tomography (SD-OCT) scans. METHODS: HD-OCT (Cirrus; Carl Zeiss
      Meditec, Dublin, CA) volume scans (512 * 128) were retrospectively collected from
      46 eyes of 33 patients with evidence of PED in the setting of age-related macular
      degeneration (AMD, n = 28) or central serous chorioretinopathy (CSCR, n = 5). In
      these eyes, 168 PEDs were automatically detected with a system-associated tool
      (Cirrus HD-OCT RPE Elevation Analysis; Carl Zeiss Meditec). Two independent,
      certified Doheny Image Reading Center (DIRC) OCT graders classified these PEDs
      into three categories--serous, drusenoid, or fibrovascular--via inspection of the
      B-scans. Manual classification results served as the gold standard for
      comparisons with automated classification. For automated classification,
      interindividual variation in intensities was normalized in all images. Individual
      A-scans within the detected PEDs were then automatically classified into one of
      three categories based on the mean internal intensity and the standard deviation
      of the internal intensity: mean intensity <30 (serous type); mean intensity >=30
      but <60 or mean intensity >=30 and SD >=30 (fibrovascular type); or mean
      intensity >=60 and SD < 30 (drusenoid type). Individual PEDs were then
      automatically classified into the same three categories based on the predominant
      type of A-scan within the PED. For mixed PEDs (many A-scans of each type), a risk
      index for neovascularization was computed based on the percentage of
      fibrovascular A-scans. In addition, a confidence index was computed for each PED
      based on its mathematical distance from the PED category boundaries. RESULTS:
      Among the 168 PEDs, the DIRC graders classified 16 as serous, 88 as
      fibrovascular, and 64 as drusenoid PEDs. The automated algorithm classified 14 as
      serous, 96 as fibrovascular, and 58 as drusenoid PEDs. The sensitivity and
      specificity values for automated classification according to type of PED were 88%
      and 100% for serous, 76% and 64% for fibrovascular, and 58% and 81% for
      drusenoid, respectively. CONCLUSIONS: Automated classification of PEDs using
      internal reflectivity characteristics appears to be sensitive for detecting
      serous and fibrovascular PEDs. Automated classification and quantification of
      PEDs may be a useful tool in future studies for stratifying PEDs according to
      risk and possibly predicting the risk of advanced AMD.

PMID- 22159020
TI  - Retinal function and structure in the hypotransferrinemic mouse.
AB  - PURPOSE: The iron carrier transferrin is expressed at remarkably high levels in
      normal retinas and is upregulated during retinal degeneration. The authors
      characterized the consequences of genetically reduced retinal transferrin
      production on retinal structure and function. METHODS: Hypotransferrinemic (HPX-/
      ) mice treated with weekly intraperitoneal salvage transferrin injections were
      examined at 1 and 2 months of age. HPX-/-, HPX+/-, and wild-type (WT) mice were
      evaluated by electroretinography, ophthalmoscopy, and histology. Retinal iron
      content and transferrin levels were measured. RNA levels of genes involved in
      iron homeostasis and antioxidative response were determined by quantitative PCR.
      Oxidative injury was assessed by immunostaining for 4-hydroxy-2-nonenal (HNE).
      RESULTS: At 2 months, dark-adapted, mixed rod-cone response b-wave amplitudes
      were significantly lower in HPX-/- mice than in WT mice (340 +/- 112 MUV vs. 624
      +/- 134 MUV [mean +/- SEM]; P = 0.002). Oscillatory potentials were significantly
      suppressed in HPX mice, and ophthalmoscopy demonstrated marked retinal pallor.
      Quantitative immunostaining revealed a 39% reduction of transferrin content in
      HPX-/- compared with WT retinas (P = 0.01). mRNA levels of Tf, Tf receptor, and
      ceruloplasmin were decreased, whereas mRNA for antioxidant genes were elevated in
      HPX-/- retinas. HNE staining was reduced in mice carrying the mutant HPX allele.
      Histologic examination demonstrated preserved retinal structure, and retinal iron
      content was similar across the strains. CONCLUSIONS: Despite the lack of wild
      type retinal transferrin production and low levels of retinal transferrin
      protein, the retinal morphology and retinal iron content in HPX-/- mice treated
      by systemic salvage transferrin injections are normal until age 2 months.
      However, retinal function and gene expression of some of the iron-associated
      genes are significantly altered.

PMID- 22159021
TI  - Physiological and toxicological effects of cefuroxime on the albino rabbit
      retina.
AB  - PURPOSE: Intracameral cefuroxime was found to lower the risk of endophthalmitis
      after cataract surgery. The purpose of this study was to evaluate the retinal
      toxicity of cefuroxime in a rabbit model. METHODS: Twenty-two albino rabbits were
      divided into two cefuroxime groups: low-dose (1mg/0.1 mL, n = 9) and high dose
      (10 mg/0.1 mL, n = 13). The right eye of each rabbit was injected with 0.1 mL
      cefuroxime solution (experimental eye) and the left eye with 0.1 mL saline
      (control eye). Electroretinogram (ERG) responses were recorded at 3 hours, 4
      days, and 1, 2, and 4 weeks after injection. After 4 weeks, the rabbits were
      euthanized, the eyes were enucleated, and the retinas were prepared for
      histologic evaluation and GFAP immunostaining. RESULTS: No functional (ERG) or
      histologic damage was found in rabbits in the low-dose group. In the high-dose
      group, a significant decrease in the ERG amplitudes of the experimental eyes was
      seen 3 hours after injection, followed by partial recovery during 4 weeks of
      follow-up. Retinal histology of experimental eyes revealed marked damage. GFAP
      immunoreactivity in Muller cells was expressed in rabbits belonging to both
      groups, although it was more extensive in the high-dose group. CONCLUSIONS: ERG
      and histologic findings indicated that a dose of 1 mg cefuroxime, administered
      intravitreally, was not toxic to the rabbit retina. A dose of 10 mg, injected
      intravitreally, induced transient physiological effects, and was toxic to the
      rabbit retina, as was evident by the permanent reduction in the ERG responses and
      by the structural damage to the retina with signs of glial activation.

PMID- 22159022
TI  - Therapeutic effects of epidermal growth factor on benzalkonium chloride-induced
      dry eye in a mouse model.
AB  - PURPOSE: To investigate the therapeutic effects and possible mechanisms of
      epidermal growth factor (EGF) on the mouse dry eye model induced by benzalkonium
      chloride (BAC). METHODS: The eye drop containing EGF was topically administered
      (3 ng per day) on a BAC-induced dry eye model. The following clinical indications
      of dry eye were evaluated on Days 2, 4, and 6: tear break-up time (BUT), corneal
      fluorescein staining, inflammatory index, and tear volume. Global specimens were
      collected on Day 6 and then the following examinations were performed: histologic
      investigation, TUNEL assay to measure the dead cells, periodic acid-schiff (PAS)
      assay to detect goblet cells, and immunostaining of antibodies of Ki-67, EGF
      receptor (EGFR), and MUC1 in the corneas. The levels of EGFR and p-ERK of the
      corneas were also measured by Western blot analysis. RESULTS: EGF resulted in
      longer BUTs on Days 2 and 6, lower fluorescein staining scores on Days 4 and 6,
      while no significant changes in inflammatory index or tear volume. EGF induced
      higher EGFR expression in corneal tissues by immunofluorescent staining and
      Western blot analysis. EGF also upregulated p-ERK, increased Ki-67 positive
      cells, and decreased TUNEL positive cells. In addition, EGF significantly
      increased the goblet cells number and MUC1 expression in the epithelium.
      CONCLUSIONS: Topical application of EGF presented clinical improvements on dry
      eye by stabilizing the tear film and maintaining the integrity of epithelium. The
      results indicate that EGF has potential as a therapeutic agent in clinical
      treatment of dry eye.

PMID- 22159023
TI  - Diffusion tensor imaging detected optic nerve injury correlates with decreased
      compound action potentials after murine retinal ischemia.
AB  - PURPOSE: This study evaluated the function of mouse optic nerves after transient
      retinal ischemia using in vitro electrophysiologic recordings of compound action
      potentials (CAPs) correlated with diffusion tensor imaging (DTI) injury markers
      with confirmation by immunohistochemistry-determined pathology. METHODS: Retinal
      ischemia was induced in 7- to 8-week-old female C57BL/6 mice by elevating
      intraocular pressure to 110 mm Hg for 60 minutes. At 3 and 7 days after retinal
      ischemia, optic nerves were removed for CAP measurements. The CAP amplitude was
      recorded using suction electrodes in isolated control and injured optic nerves
      followed by ex vivo DTI evaluation. After DTI, optic nerves were embedded in
      paraffin and cut for immunohistochemical analyses. RESULTS: Consistent with
      previous in vivo DTI measurements, a 25% decrease in axial diffusivity with
      normal radial diffusivity was seen at 3 days after retinal ischemia, suggesting
      axonal injury without myelin damage. At 7 days, there was no additional change in
      axial diffusivity compared with that at 3 days, but radial diffusivity
      significantly increased by 50%, suggestive of significant myelin damage due to
      sustained axonal injury. The relative anisotropy (RA) progressively decreased
      after retinal ischemia when compared with that of the controls. The CAP amplitude
      in injured nerves also progressively decreased after retinal ischemia, which
      correlated with the reduced RA (r = 0.80). CONCLUSIONS: This study suggests that
      CAP amplitude reflects both axonal and myelin integrity and RA is an optimal
      parameter for functional assessment compared with axial or radial diffusivity
      alone in murine optic nerves after retinal ischemia.

PMID- 22159025
TI  - Cyano-bridged terbium(III)-chromium(III) bimetallic quasi-one-dimensional
      assembly exhibiting long-range magnetic ordering.
AB  - A new cyano-bridged Tb(III)-Cr(III) heterometallic complex
      [Tb(H(2)O)(2)(DMF)(4){Cr(CN)(6)}].H(2)O (DMF = dimethylformamide) (1), assembled
      from paramagnetic hexacyanochromium(III) [Cr(CN)(6)](3-) building block and
      highly anisotropic terbium(III) ion has been prepared and structurally and
      magnetically characterized. Complex 1 shows one-dimensional (1D) zig-zag chain
      like structural motif which is further extended into three-dimensional network
      through hydrogen-bonding interactions. The long-range magnetic ordering observed
      in complex 1, which is possibly due to interchain magnetic dipolar interactions,
      illuminates that this complex is a molecule-based magnet with critical
      temperature of about 5 K. This higher critical temperature among those of Ln(III)
      Cr(III) heterometallic complexes exhibiting long-range magnetic ordering is
      probably due to the introduction of highly anisotropic terbium(III) ion.

PMID- 22159024
TI  - Effect of circadian clock gene mutations on nonvisual photoreception in the
      mouse.
AB  - PURPOSE: Mice lacking rods and cones retain pupillary light reflexes that are
      mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs).
      Melanopsin is necessary and sufficient for this nonvisual photoreception. The
      mammalian inner retina also expresses the potential blue light photopigments
      cryptochromes 1 and 2. Previous studies have shown that outer retinal degenerate
      mice lacking cryptochromes have lower nonvisual photic sensitivity than retinal
      degenerate mice, suggesting a role for cryptochrome in inner retinal
      photoreception. METHODS: Nonvisual photoreception (pupillary light responses,
      circadian entrainment, and in vitro sensitivity of intrinsically photosensitive
      retinal ganglion cells) were studied in wild-type, rd/rd, and circadian clock
      mutant mice with and without rd/rd mutation. RESULTS: Loss of cryptochrome in
      retinal degenerate mice reduces the sensitivity of the pupillary light response
      at all wavelengths but does not alter the form of the action spectrum, suggesting
      that cryptochrome does not function as a photopigment in the inner retina. The
      authors compounded the rd/rd retinal degeneration mutation with mutations in
      other essential circadian clock genes, mPeriod and Bmal1. Both mPeriod1-/-;
      mPeriod2-/-;rd/rd and Bmal1-/-;rd/rd mice showed significantly lower pupillary
      light sensitivity than rd/rd mice alone. A moderate amplitude (0.5 log) circadian
      rhythm of pupillary light responsiveness was observed in rd/rd mice.
      Multielectrode array recordings of ipRGC responses of mCryptochrome1-/
      ;mCryptochrome2-/- and mPeriod1-/-;mPeriod2-/- mice showed minimal sensitivity
      decrement compared with wild-type animals. mCryptochrome1-/-;mCryptochrome2-/
      ;rd/rd, mPeriod1-/-;mPeriod2-/-;rd/rd and Bmal1-/-;rd/rd mice all showed
      comparable weak behavioral synchronization to a 12-hour light/12-hour dark cycle.
      CONCLUSIONS: The effect of cryptochrome loss on nonvisual photoreception is due
      to loss of the circadian clock nonspecifically. The circadian clock modulates the
      sensitivity of nonvisual photoreception.

PMID- 22159026
TI  - Bubbles no more: in-plane trapping and removal of bubbles in microfluidic
      devices.
AB  - Gas bubbles present a frequent challenge to the on-chip investigation and culture
      of biological cells and small organs. The presence of a single bubble can
      adversely impair biological function and often viability as it increases the wall
      shear stress in a liquid-perfused microchannel by at least one order of
      magnitude. We present a microfluidic strategy for in-plane trapping and removal
      of gas bubbles with volumes of 0.1-500 nL. The presented bubble trap is
      compatible with single-layer soft lithography and requires a footprint of less
      than ten square millimetres. Nitrogen bubbles were consistently removed at a rate
      of 0.14 MUL min(-1). Experiments were complemented with analytical and numerical
      models to comprehensively characterize bubble removal for liquids with different
      wetting behaviour. Consistent long-term operation of the bubble trap was
      demonstrated by removing approximately 4000 bubbles during one day. In a case
      study, we successfully applied the bubble trap to the on-chip investigation of
      intact small blood vessels. Scalability of the design was demonstrated by
      realizing eight parallel traps at a total removal rate of 0.9 MUL min(-1)
      (measured for nitrogen).

PMID- 22159028
TI  - Synthesis of efficient N-containing TiO2 photocatalysts with high anatase thermal
      stability and the effects of the nitrogen residue on the photoinduced charge
      separation.
AB  - Efficient N-containing TiO(2) nanoparticles with high anatase thermal stability
      were synthesized via a hexamethylenetetramine (HMT)-modified sol-hydrothermal
      process. The results showed that modification with proper amounts of HMT is
      effective in increasing the onset temperature of the phase transformation of
      TiO(2) from anatase to rutile. The enhancement of the anatase thermal stability
      of the modified TiO(2) was attributed to ammonia produced slowly by hydrolysis of
      the HMT molecules in the sol-hydrothermal process and, additionally, to the
      residual nitrogen species after the thermal treatment at high temperatures, as
      indicated by the XPS examination. Compared with the unmodified TiO(2), the
      modified TiO(2) obtained by a thermal treatment at high temperatures exhibited
      good photocatalytic performance under UV light and was found to even be superior
      to the commercially available P25-TiO(2). It was suggested that the residual N
      species (Ti-O-N), formed after the thermal treatment at high temperatures, along
      with the mixed phase composition, large surface area and the increase in the
      thermal stability, were responsible for the enhanced photocatalytic activity of
      modified TiO(2). It was demonstrated, by means of the surface photovoltage
      responses of the modified TiO(2) in different atmospheres along with the aid of
      an outer electric field, that the residual N species could effectively capture
      the photoinduced holes, which was favorable for the effective separation of the
      photoinduced charges. This work provides a feasible route to fabricate high
      performance TiO(2)-based functional nanomaterials with high anatase thermal
      stability.

PMID- 22159027
TI  - Soil mineralization of two-phase olive mill wastes: effect of the lignocellulosic
      composition on soil C dynamics.
AB  - The low degradation rate of two-phase olive mill wastes (TPOMW) during composting
      and after soil application is a characteristic feature of these materials. The
      aim of this work was to evaluate the relationship between the lignocellulosic
      fraction of TPOMW and the organic matter (OM) degradation rate in three
      agricultural soils amended with four TPOMW composting mixtures at different
      degree of stabilisation and prepared with different bulking agents and N sources.
      The mineralisation kinetics of TPOMW composting mixtures in soil reflected a
      large amount of slowly mineralisable C even in the starting mixtures (I and T1)
      where this fraction represented up to 85% of the total potentially mineralisable
      C pool. The effect of rich lignocellulosic composition was confirmed by the study
      of the DTS (50% dry TPOMW + 50% sheep manure) mixtures prepared with dry TPOMW,
      which had undergone partial degradation in a storage pond for one year before
      composting. These DTS samples showed a more similar kinetic behaviour in soil
      than the more transformed composting mixtures as reflected in the principal
      component analysis (PCA) diagram, where they were grouped in the same quadrant
      dominated by the lignin/holocellulose ratio. Soils amended with mature composts
      evolved very low amounts of C (between 2 and 6% of the added C) after two months
      of incubation, which highlights the suitability of these materials as a suitable
      C source for the soil to promote long term soil C stabilisation.

PMID- 22159029
TI  - Ab initio calculations of the melting temperatures of refractory bcc metals.
AB  - We present ab initio calculations of the melting temperatures for bcc metals Nb,
      Ta and W. The calculations combine phase coexistence molecular dynamics (MD)
      simulations using classical embedded-atom method potentials and ab initio density
      functional theory free energy corrections. The calculated melting temperatures
      for Nb, Ta and W are, respectively, within 3%, 4%, and 7% of the experimental
      values. We compare the melting temperatures to those obtained from direct ab
      initio molecular dynamics simulations and see if they are in excellent agreement
      with each other. The small remaining discrepancies with experiment are thus
      likely due to inherent limitations associated with exchange-correlation energy
      approximations within density-functional theory.

PMID- 22159030
TI  - Evaluating the evidence for the implementation of C-reactive protein measurement
      in adult patients with suspected lower respiratory tract infection in primary
      care: a systematic review.
AB  - BACKGROUND: Excessive prescription of antibiotics in patients with lower
      respiratory tract infection (LRTI) is common in primary care and might be reduced
      by rapid point-of-care (POC) C-reactive protein (CRP) testing. However, the exact
      benefits of this test are unclear. OBJECTIVE: To review the available evidence
      for the role of POC CRP measurement in (i) guiding antibiotic prescription, (ii)
      predicting aetiology, (iii) prognosis and (iv) diagnosis (pneumonia) in LRTI
      patients. METHODS: For each research question, studies were retrieved through an
      electronic literature search in Medline, Embase and the Cochrane Library using
      synonyms for CRP and LRTI combined with different relevant subheadings. Study
      quality was assessed using validated instruments and predefined outcome measures
      were extracted from each study. RESULTS: The search yielded 13 articles, each
      answering one or more questions; one was excluded by insufficient internal
      validity. (i) One of four studies showed a significant reduction in the
      antibiotic prescriptions when applying POC CRP measurement [relative risk (RR)
      0.6, 95% confidence interval (CI) 0.5-0.7]. (ii) Three studies on aetiology
      demonstrated that an elevated CRP was associated with bacterial [odds ratio (OR)
      2.46-4.8] and one with viral (OR 2.7) aetiology. (iii) Results on the prognostic
      value were contradictory, providing evidence for faster symptom resolution (RR
      1.16, 95% CI 1.1-1.3), higher mortality rate (RR 2.5, 95% CI 1.2-5.1) and no
      difference in outcome in patients with high CRP levels. (iv) Four studies showed
      that CRP had limited value as a single predictor of pneumonia. When combined with
      clinical assessment, its value increased according to two of these studies
      (receiver operating characteristic area from 0.7 to 0.9). However, methodological
      flaws and/or wide CIs limit the generalizability of findings in all studies.
      CONCLUSION: The evidence for the benefits of POC CRP measurement in LRTI patients
      in primary care is limited, contradictory and does not support its use to guide
      treatment decisions yet.

PMID- 22159031
TI  - Heat shock protein 47 stress responses in Chinese hamster ovary cells exposed to
      raw and reclaimed wastewater.
AB  - As wastewater reclamation and reuse becomes more widespread, risks of exposure to
      treated wastewater increase. Moreover, an unlimited number of pollutants can be
      identified in wastewater. Therefore, comprehensive toxicity assessment of treated
      wastewater is imperative. The objective of this study was to perform a
      comprehensive toxicity assessment of wastewater treatment systems using stress
      response bioassays. This powerful tool can comprehensively assess the toxicity of
      contaminants. In this study, samples from conventional activated sludge
      treatment, membrane bioreactors (MBRs) with different pore sizes and sludge
      retention times (SRTs), rapid sand filtration, coagulation, nano-filtration (NF)
      and reverse osmosis (RO) were investigated. The results of stress response
      bioassays confirmed that the secondary effluent showed higher stress response
      than influent indicating that biological treatment generates toxic compounds. The
      results obtained from molecular weight fractionation of water samples
      demonstrated that organic matter with a higher molecular weight fraction (>0.1
      MUm) causes toxicity in secondary effluent. Furthermore, supernatant from MBR
      reactors showed toxicity regardless of SRT. On the other hand, stress response
      was not detected in MBR permeates except for an MBR equipped with a larger pore
      size membrane (0.4 MUm) and with a short SRT (12 days). While rapid sand
      filtration could not remove the toxic compounds found in secondary effluent,
      coagulation tests, operated at an appropriate pH, were effective for reducing
      stress response in the secondary effluent. Experimental findings also showed that
      stress response was not detected in cases of NF and RO permeate subsequent to MBR
      treatment.

PMID- 22159032
TI  - Fully automated cellular-resolution vertebrate screening platform with parallel
      animal processing.
AB  - The zebrafish larva is an optically-transparent vertebrate model with complex
      organs that is widely used to study genetics, developmental biology, and to model
      various human diseases. In this article, we present a set of novel technologies
      that significantly increase the throughput and capabilities of our previously
      described vertebrate automated screening technology (VAST). We developed a robust
      multi-thread system that can simultaneously process multiple animals. System
      throughput is limited only by the image acquisition speed rather than by the
      fluidic or mechanical processes. We developed image recognition algorithms that
      fully automate manipulation of animals, including orienting and positioning
      regions of interest within the microscope's field of view. We also identified the
      optimal capillary materials for high-resolution, distortion-free, low-background
      imaging of zebrafish larvae.

PMID- 22159034
TI  - Crawling cell locomotion revisited.

PMID- 22159033
TI  - Actin disassembly clock determines shape and speed of lamellipodial fragments.
AB  - A central challenge in motility research is to quantitatively understand how
      numerous molecular building blocks self-organize to achieve coherent shape and
      movement on cellular scales. A classic example of such self-organization is
      lamellipodial motility in which forward translocation is driven by a treadmilling
      actin network. Actin polymerization has been shown to be mechanically restrained
      by membrane tension in the lamellipodium. However, it remains unclear how
      membrane tension is determined, what is responsible for retraction and shaping of
      the rear boundary, and overall how actin-driven protrusion at the front is
      coordinated with retraction at the rear. To answer these questions, we utilize
      lamellipodial fragments from fish epithelial keratocytes which lack a cell body
      but retain the ability to crawl. The absence of the voluminous cell body in
      fragments simplifies the relation between lamellipodial geometry and cytoskeletal
      dynamics. We find that shape and speed are highly correlated over time within
      individual fragments, whereby faster crawling is accompanied by larger front-to
      rear lamellipodial length. Furthermore, we find that the actin network density
      decays exponentially from front-to-rear indicating a constant net disassembly
      rate. These findings lead us to a simple hypothesis of a disassembly clock
      mechanism in which rear position is determined by where the actin network has
      disassembled enough for membrane tension to crush it and haul it forward. This
      model allows us to directly relate membrane tension with actin assembly and
      disassembly dynamics and elucidate the role of the cell membrane as a global
      mechanical regulator which coordinates protrusion and retraction.

PMID- 22159036
TI  - Is 11beta-HSD1 expressed in islet beta-cells and regulated by corticotropin
      releasing hormone?

PMID- 22159035
TI  - Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1)
      retrotransposition in human neural stem cells.
AB  - Long interspersed element-1 (L1) retrotransposons compose ~20% of the mammalian
      genome, and ongoing L1 retrotransposition events can impact genetic diversity by
      various mechanisms. Previous studies have demonstrated that endogenous L1
      retrotransposition can occur in the germ line and during early embryonic
      development. In addition, recent data indicate that engineered human L1s can
      undergo somatic retrotransposition in human neural progenitor cells and that an
      increase in human-specific L1 DNA content can be detected in the brains of normal
      controls, as well as in Rett syndrome patients. Here, we demonstrate an increase
      in the retrotransposition efficiency of engineered human L1s in cells that lack
      or contain severely reduced levels of ataxia telangiectasia mutated, a
      serine/threonine kinase involved in DNA damage signaling and neurodegenerative
      disease. We demonstrate that the increase in L1 retrotransposition in ataxia
      telangiectasia mutated-deficient cells most likely occurs by conventional target
      site primed reverse transcription and generate either longer, or perhaps more, L1
      retrotransposition events per cell. Finally, we provide evidence suggesting an
      increase in human-specific L1 DNA copy number in postmortem brain tissue derived
      from ataxia telangiectasia patients compared with healthy controls. Together,
      these data suggest that cellular proteins involved in the DNA damage response may
      modulate L1 retrotransposition.

PMID- 22159037
TI  - Mechanistic insights into beta-oxygen atom transfer in olefin epoxidation
      mediated by W(VI) complexes and H2O2.
AB  - A DFT investigation of the olefin epoxidation mechanism catalysed by the
      [Cp*WO(OH)(2)](+) complex with H(2)O(2) reveals that the outer sphere transfer of
      the hydroperoxido O(beta) atom to the olefin is considerably more favourable than
      that of the hydroperoxido O(alpha) atom. The reasons for this unusual pathway are
      discussed.

PMID- 22159038
TI  - Not4 enhances JAK/STAT pathway-dependent gene expression in Drosophila and in
      human cells.
AB  - The JAK/STAT pathway is essential for organogenesis, innate immunity, and stress
      responses in Drosophila melanogaster. The JAK/STAT pathway and its associated
      regulators have been highly conserved in evolution from flies to humans. We have
      used a genome-wide RNAi screen in Drosophila S2 cells to identify regulators of
      the JAK/STAT pathway, and here we report the characterization of Not4 as a
      positive regulator of the JAK/STAT pathway. Overexpression of Not4 enhanced
      Stat92E-mediated gene responses in vitro and in vivo in Drosophila. Specifically,
      Not4 increased Stat92E-mediated reporter gene activation in S2 cells; and in
      flies, Not4 overexpression resulted in an 8-fold increase in Turandot M (TotM)
      and in a 4-fold increase in Turandot A (TotA) stress gene activation when
      compared to wild-type flies. Drosophila Not4 is structurally related to human
      CNOT4, which was found to regulate interferon-gamma- and interleukin-4-induced
      STAT-mediated gene responses in human HeLa cells. Not4 was found to
      coimmunoprecipitate with Stat92E but not to affect tyrosine phosphorylation of
      Stat92E in Drosophila cells. However, Not4 is required for binding of Stat92E to
      its DNA recognition sequence in the TotM gene promoter. In summary, Not4/CNOT4 is
      a novel positive regulator of the JAK/STAT pathway in Drosophila and in humans.

PMID- 22159039
TI  - Metal-free activation of H2O2 by g-C3N4 under visible light irradiation for the
      degradation of organic pollutants.
AB  - Semiconducting carbon nitride materials were successfully prepared via a thermal
      poly-condensation of dicyandiamide as a precursor at >500  degrees C. The
      resulting materials were investigated as metal-free catalysts for the activation
      of H(2)O(2) with visible light under mild conditions, using the decomposition of
      Rhodamine B (RhB) in aqueous solution as a model reaction. Results revealed that
      carbon nitride catalysts can activate H(2)O(2) to generate reactive oxy-radicals
      under visible light irradiation without employment of any metal additives,
      leading to the mineralization of the dye. Factors affecting the degradation of
      organic compounds are pH values and the concentration of H(2)O(2). Recycling of
      the catalyst indicated no obvious deactivation during the entire catalytic
      reaction, indicating good (photo)chemical stability of metal-free polymeric
      carbon nitride photocatalysts for environmental purification. This study
      demonstrated a promising approach for the activation of green oxidant, hydrogen
      peroxide, by the newly-developed polymer photocatalysts for environmental
      remediation and oxidation catalysis.

PMID- 22159040
TI  - Chiral nickel(II) complexes in the preparation of 11C- and 18F-labelled
      enantiomerically pure alpha-amino acids.
AB  - Positron emission tomography (PET) utilises positron emitting
      radiopharmaceuticals in the study of metabolic and physiological processes. FDG
      PET is a useful technique for tumour detection; however FDG has disadvantages.
      The incorporation of labelled amino acids into brain tumours and into some other
      organs with high physiological consumption of glucose is a superior diagnostic
      method due to its much higher selectivity compared to FDG. A Ni(II) complex with
      a Schiff base of BPB and glycine was one of the first glycine synthons used for
      asymmetric synthesis of carbon-11 and fluorine-18 labelled alpha-amino acids. A
      similar complex was employed for routine preparation of [(18)F]FET. Physico
      chemical investigations allowed us to design modified complexes with much
      stronger stereodiscriminative power including stereospecific ones. Chiral nickel
      complexes are also used for the preparation of tailored amino acids for the
      incorporation into peptides followed by labelling the peptides with fluorine-18
      labelled "click" reagents. This review covers PET applications of Ni(II)
      complexes of Schiff base of BPB and alpha-amino acids from 1989 to date.

PMID- 22159041
TI  - Trinuclear Cu(II) complexes of a chiral N6O3 amine.
AB  - Enantiopure trinuclear Cu(II) complexes 3 and 4 of macrocyclic amine 1 derived
      from the 3 + 3 condensation of 2,6-diformyl-4-methylphenol and (1S,2S)-1,2
      diaminocyclohexane have been synthesized and characterized by ESI MS and NMR
      spectroscopy. The X-ray crystal structures of both complexes have been
      determined. The structure of the chloride derivative 3 indicates unusual
      combination of distorted tetragonal bipyramidal, square pyramidal and square
      geometries of the three Cu(II) ions bound by macrocycle 1. The acetate complex 4
      also exhibits unsymmetrical trinuclear core with the bridging and terminal
      acetate anions. The complexation of Cu(II) ions by macrocycle 1 has been studied
      using potentiometric methods and both protonation and binding constants of 1 have
      been determined. The distribution of the complex forms indicates cooperative
      binding of three metal ions by 1. The overall magnetic behaviour for 3
      corresponds to an antiferromagnetically coupled triangular system. Compound 4
      shows the presence of antiferromagnetic coupling (J = -74.9(1) cm(-1)) between
      the metal centers in equilateral triangular array.

PMID- 22159042
TI  - Distillation and detection of SO2 using a microfluidic chip.
AB  - A miniaturized distillation system is presented for separating sulfurous acid
      (H(2)SO(3)) into sulfur dioxide (SO(2)) and water (H(2)O). The major components
      of the proposed system include a microfluidic distillation chip, a power control
      module, and a carrier gas pressure control module. The microfluidic chip is
      patterned using a commercial CO(2) laser and comprises a serpentine channel, a
      heating zone, a buffer zone, a cooling zone, and a collection tank. In the
      proposed device, the H(2)SO(3) solution is injected into the microfluidic chip
      and is separated into SO(2) and H(2)O via an appropriate control of the
      distillation time and temperature. The gaseous SO(2) is then transported into the
      collection chamber by the carrier gas and is mixed with DI water. Finally, the
      SO(2) concentration is deduced from the absorbance measurements obtained using a
      spectrophotometer. The experimental results show that a correlation coefficient
      of R(2) = 0.9981 and a distillation efficiency as high as 94.6% are obtained for
      H(2)SO(3) solutions with SO(2) concentrations in the range of 100-500 ppm. The
      SO(2) concentrations of two commercial red wines are successfully detected using
      the developed device. Overall, the results presented in this study show that the
      proposed system provides a compact and reliable tool for SO(2) concentration
      measurement purposes.

PMID- 22159043
TI  - Quantifying dissipative contributions in nanoscale interactions.
AB  - Imaging with nanoscale resolution has become routine practice with the use of
      scanning probe techniques. Nevertheless, quantification of material properties
      and processes has been hampered by the complexity of the tip-surface interaction
      and the dependency of the dynamics on operational parameters. Here, we propose a
      framework for the quantification of the coefficients of viscoelasticity, surface
      energy, surface energy hysteresis and elastic modulus. Quantification of these
      parameters at the nanoscale will provide a firm ground to the understanding and
      modelling of tribology and nanoscale sciences with true nanoscale resolution.

PMID- 22159044
TI  - Diverse lanthanide coordination polymers tuned by the flexibility of ligands and
      the lanthanide contraction effect: syntheses, structures and luminescence.
AB  - Two new flexible exo-bidentate ligands were designed and synthesized,
      incorporating different backbone chain lengths bearing two salicylamide arms,
      namely 2,2'-(2,2'-oxybis(ethane-2,1-diyl)bis(oxy))bis(N-benzylbenzamide) (L(I))
      and 2,2'-(2,2'-(ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis(oxy)bis(N
      benzylbenzamide) (L(II)). These two structurally related ligands are used as
      building blocks for constructing diverse lanthanide polymers with luminescent
      properties. Among two series of lanthanide nitrate complexes which have been
      characterized by elemental analysis, TGA analysis, X-ray powder diffraction, and
      IR spectroscopy, ten new coordination polymers have been determined using X-ray
      diffraction analysis. All the coordination polymers exhibit the same metal-to
      ligand molar ratio of 2 : 3. L(I), as a bridging ligand, reacts with lanthanide
      nitrates forming two different types of 2D coordination complexes: herringbone
      framework {[Ln(2)(NO(3))(6)(L(I))(3).mC(4)H(8)O(2)](infinity) (Ln = La (1), and
      Pr (2), m = 1, 2)} as type I,; and honeycomb framework
      {[Ln(2)(NO(3))(6)(L(I))(3).nCH(3)OH](infinity) (Ln = Nd (3), Eu (4), Tb (5), and
      Er (6), n = 0 or 3)} as type II, which change according to the decrease in radius
      of the lanthanide. For L(II), two distinct structure types of 1D ladder-like
      coordination complexes were formed with decreasing lanthanide radii:
      [Ln(2)(NO(3))(6)(L(II))(3).2C(4)H(8)O(2)](infinity) (Ln = La (7), Pr (8), Nd (9))
      as type III, [Ln(2)(NO(3))(6)(L(I))(3).mC(4)H(8)O(2).nCH(3)OH](infinity) (Ln = Eu
      (10), Tb (11), and Er (12), m, n = 2 or 0) as type IV. The progressive structural
      variation from the 2D supramolecular framework to 1D ladder-like frameworks is
      attributed to the varying chain length of the backbone group in the flexible
      ligands. The photophysical properties of trivalent Sm, Eu, Tb, and Dy complexes
      at room temperature were also investigated in detail.

PMID- 22159045
TI  - Explaining statin inhibition effectiveness of HMG-CoA reductase by quantum
      biochemistry computations.
AB  - By taking advantage of the crystallographic data of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMGR) complexed with statins, a quantum biochemistry study
      based on the density functional theory is performed to estimate the interaction
      energy for each statin when one considers binding pockets of different sizes.
      Assuming a correlation between statin potency and the strength of the total HMGR
      statin binding energy, clinical data as well as IC(50) values of these
      cholesterol-lowering drugs are successfully explained only after stabilization of
      the calculated total binding energy for a larger size of the ligand-interacting
      HGMR region, one with a radius of at least 12.0 A. Actually, the binding pocket
      radius suggested by classic works, which was based solely on the interpretation
      of crystallographic data of the HMGR-statin complex, is smaller than that
      necessary to achieve total binding energy convergence in our simulations.
      Atorvastatin and rosuvastatin are shown to be the most strongly bound HMGR
      inhibitors, while simvastatin and fluvastatin are the weakest ones. A binding
      site, interaction energy between residues and statin atoms, and residues domain
      (BIRD) panel is constructed, indicating clear quantum biochemistry-based routes
      for the development of new statin derivatives.

PMID- 22159046
TI  - Nanoscale imaging of Bacillus thuringiensis flagella using atomic force
      microscopy.
AB  - Because bacterial flagella play essential roles in various processes (motility,
      adhesion, host interactions, secretion), studying their expression in relation to
      function is an important challenge. Here, we use atomic force microscopy (AFM) to
      gain insight into the nanoscale surface properties of two wild-type and four
      mutant strains of Bacillus thuringiensis exhibiting various levels of
      flagellation. We show that, unlike AFM in liquid, AFM in air is a simple and
      reliable approach to observe the morphological details of the bacteria, and to
      quantify the density and dimensions of their flagella. We found that the amount
      of flagella expressed by the six strains, as observed at the nanoscale,
      correlates with their microscopic swarming motility. These observations provide
      novel information on flagella expression in gram-positive bacteria and
      demonstrate the power of AFM in genetic studies for the fast assessment of the
      phenotypic characteristics of bacterial strains altered in cell surface
      appendages.

PMID- 22159047
TI  - Carrier dynamics in the luminescent states of Cd(1-x)Mn(x)S nanoparticles:
      effects of temperature and x-concentration.
AB  - Optical absorption (OA), magnetic force microscopy (MFM), and photoluminescence
      (PL) measurements were employed to study Cd(1-x)Mn(x)S nanoparticles (NPs), grown
      in a glass matrix, at different x-concentrations. The formation of two well
      defined groups of NPs with different sizes was detected by OA spectra at room
      temperature and confirmed by MFM images, from which they were identified as
      quantum dots (QDs) and bulk-like nanocrystals (NCs). Emissions from luminescent
      states were observed in the temperature dependent PL spectra of both groups of
      NPs, including those from deep defects which were attributed to the presence of
      divacancies (V(Cd)-V(S)) in the hexagonal wurtzite structure. Furthermore, we
      have come up with a model based on rate equations that describes energy transfers
      involving the excitonic states of QDs, the conduction band of bulk-like NCs, and
      the shallow virtual levels of NPs. This model was used to fit the integrated PL
      intensity of the corresponding NP groups, and a good agreement between them
      confirms that the model suitably describes the temperature dependent carrier
      dynamics of Cd(1-x)Mn(x)S NPs.

PMID- 22159048
TI  - Letter to the Editor and response.

PMID- 22159049
TI  - Studies on characterization, telomerase inhibitory properties and G-quadruplex
      binding of eta6-arene ruthenium complexes with 1,10-phenanthroline-derived
      ligands.
AB  - Two arene ruthenium complexes [Ru(eta(6)-C(6)H(6))(p-MOPIP)Cl](+)1 and [Ru(eta(6)
      C(6)H(6))(p-CFPIP)Cl](+)2, where p-MOPIP = 2-(4-methoxyphenyl)
      imidazo[4,5f][1,10] phenanthroline and p-CFPIP = 2-(4-trifluoromethylphenyl)
      imidazo[4,5f][1,10] phenanthroline, were prepared and the interactions of these
      compounds with DNA oligomers 5'-G3(T2AG3)3-3'(HTG21) have been studied by UV-vis
      and circular dichroism (CD) spectroscopy, gel mobility shift assay, fluorescence
      resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR)
      stop assay and telomeric repeat amplification protocol (TRAP) assay. The results
      show that both complexes can induce the stabilization of quadruplex DNA but
      complex 1 is a better G-quadruplex binder than complex 2. The two ruthenium
      complexes tested led to an inhibition of the enzyme telomerase and complex 1 was
      the significantly better inhibitor. A novel visual method has been developed for
      making a distinction between G-quadruplex DNA and double DNA by our Ru complexes
      binding hemin to form the hemin-G-quadruplex DNAzyme. Furthermore, in vitro
      cytotoxicity studies showed complex 1 exhibited quite potent antitumor activities
      and the greatest inhibitory selectivity against cancer cell lines.

PMID- 22159050
TI  - Clinical pathologic conference.

PMID- 22159051
TI  - No endovascular innovation without evaluation in chronic cerebrospinal venous
      insufficiency: a call for the IDEAL model.

PMID- 22159052
TI  - Magnetic resonance techniques in multiple sclerosis: the present and the future.
AB  - Magnetic resonance imaging (MRI) is sensitive to focal multiple sclerosis (MS)
      lesions. For this reason, conventional MRI measures of the burden of disease
      derived from dual-echo, fluid-attenuated inversion recovery and postcontrast T1
      weighted sequences are regularly used to monitor disease course in patients with
      confirmed MS and have been included in the diagnostic workup of patients in whom
      MS is suspected. Other quantitative magnetic resonance (MR)-based techniques with
      a higher pathological specificity (including magnetization transfer-MRI,
      diffusion tensor-MRI, and proton MR spectroscopy) have been extensively applied
      to measure disease burden within focal visible lesions and in the normal
      appearing white matter and gray matter of MS patients at different stages of the
      disease. These methods, combined with functional imaging techniques, are
      progressively improving our understanding of the factors associated with MS
      evolution. More recently, the application of new imaging modalities capable of
      measuring pathological processes related to the disease that have been neglected
      in the past (eg, iron deposition and perfusion abnormalities) and the advent of
      high- and ultrahigh-field magnets have provided further insight into the
      pathobiological features of MS. After a brief summary of the main results
      obtained from the established and emerging MR methods, this review discusses the
      steps needed before the latter become suitable for widespread use in the MS
      research community.

PMID- 22159053
TI  - Neurodegeneration across stages of cognitive decline in Parkinson disease.
AB  - OBJECTIVE: To assess regions and patterns of brain atrophy in patients with
      Parkinson disease (PD) with normal cognition (PD-NC), mild cognitive impairment
      (PD-MCI), and dementia-level cognitive deficits (PDD). DESIGN: Images were
      quantified using a region-of-interest approach and voxel-based morphometry
      analysis. We used a high-dimensional pattern classification approach to delineate
      brain regions that collectively formed the Spatial Pattern of Abnormalities for
      Recognition of PDD. SETTING: The Parkinson's Disease and Movement Disorders
      Center at the University of Pennsylvania. SUBJECTS: Eighty-four PD patients (61
      PD-NC, 12 PD-MCI, and 11 PDD) and 23 healthy control subjects (HCs) underwent
      magnetic resonance imaging of the brain. RESULTS: The PD-NC patients did not
      demonstrate significant brain atrophy compared with HCs. Compared with PD-NC
      patients, PD-MCI patients had hippocampal atrophy (beta = -0.37; P = .001), and
      PDD patients demonstrated hippocampal (beta = -0.32; P = .004) and additional
      medial temporal lobe atrophy (beta = -0.36; P = .003). The PD-MCI patients had a
      different pattern of atrophy compared with PD-NC patients (P = .04) and a similar
      pattern to that of PDD patients (P = .81), characterized by hippocampal,
      prefrontal cortex gray and white matter, occipital lobe gray and white matter,
      and parietal lobe white matter atrophy. In nondemented PD patients, there was a
      correlation between memory-encoding performance and hippocampal volume.
      CONCLUSIONS: Hippocampal atrophy is a biomarker of initial cognitive decline in
      PD, including impaired memory encoding and storage, suggesting heterogeneity in
      the neural substrate of memory impairment. Use of a pattern classification
      approach may allow identification of diffuse regions of cortical gray and white
      matter atrophy early in the course of cognitive decline.

PMID- 22159055
TI  - The APOE epsilon2 allele increases the risk of earlier age at onset in Machado
      Joseph disease.
AB  - OBJECTIVE: To investigate a modulating effect of the apolipoprotein E (APOE)
      polymorphism on age at onset of Machado-Joseph disease (MJD). DESIGN: We
      collected blood samples from 192 patients with MJD and typed the APOE
      polymorphism. Patients The 192 patients with MJD included 59 from the Azores, 73
      from mainland Portugal, and 60 from Brazil. SETTING: Academic research center.
      RESULTS: Cases with the epsilon2/epsilon3 genotype had an earlier onset compared
      with those with the epsilon3/epsilon3 or the epsilon3/epsilon4 genotype. In this
      series of patients, the presence of an APOE epsilon2 allele implies a decrease of
      nearly 5 years in the age at onset. When combining several other predictors in a
      general linear model, namely, the presence/absence of the APOE epsilon2 allele,
      with the size of the (CAG)(n) in expanded alleles, the model was significantly
      improved and the explanation of onset variance was raised from 59.8% to 66.5%.
      Furthermore, the presence of the epsilon2 allele was associated with an onset
      before age 39 years (odds ratio, 5.00; 95% CI, 1.18-21.14). CONCLUSION: The
      polymorphism at the APOE gene plays a role as a genetic modifier of MJD
      phenotype.

PMID- 22159056
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy affecting an African American man: identification of a novel
      15-base pair NOTCH3 duplication.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is the best characterized genetic cause of
      vascular dementia and stroke and has been extensively reported in European and
      Asian populations. OBJECTIVE: To report the pathological and genetic analysis of
      CADASIL in an African American man with a 15-base pair NOTCH3 duplication.
      DESIGN: Case report. SETTING: University hospital. PATIENT: A 78-year-old man
      with dementia, recurrent strokes, a family history of similar neurological
      disease, and white matter abnormalities seen on brain magnetic resonance imaging.
      MAIN OUTCOME MEASURES: Brain pathology and genetic analysis of NOTCH3. RESULTS:
      The patient's brain showed widespread arteriopathy in large and small arteries.
      Using electron microscopy, granular osmiophilic material typical of CADASIL was
      identified abutting the plasma membrane of smooth muscle cells. Brain extracts
      contained elevated NOTCH3 protein levels. Sequencing of the NOTCH3 gene revealed
      a novel 15-base pair heterozygous duplication in exon 7, which is predicted to
      direct expression of a protein that contains 5 extra amino acids, including a
      cysteine residue. CONCLUSIONS: To our knowledge, this is the first reported
      pathological and genetic analysis of an African American patient with CADASIL.
      The mutation in NOTCH3 is the longest duplication within this gene yet reported.

PMID- 22159054
TI  - A comprehensive genetic association study of Alzheimer disease in African
      Americans.
AB  - OBJECTIVES: To evaluate the association of genetic variation with late-onset
      Alzheimer disease (AD) in African Americans, including genes implicated in recent
      genome-wide association studies of whites. DESIGN: We analyzed a genome-wide set
      of 2.5 million imputed markers to evaluate the genetic basis of AD in an African
      American population. SUBJECTS: Five hundred thirteen well-characterized African
      American AD cases and 496 cognitively normal African American control subjects.
      SETTING: Data were collected from multiple sites as part of the Multi
      Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study and the
      Henry Ford Health System as part of the Genetic and Environmental Risk Factors
      for Alzheimer Disease Among African Americans (GenerAAtions) Study. RESULTS:
      Several significant single-nucleotide polymorphisms (SNPs) were observed in the
      region of the apolipoprotein E gene (APOE). After adjusting for the confounding
      effects of APOE genotype, one of these SNPs, rs6859 in PVRL2, remained
      significantly associated with AD (P = .0087). Association was also observed with
      SNPs in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, although the effect
      direction for some SNPs and the most significant SNPs differed from findings in
      data sets consisting of whites. Finally, using the African American genome-wide
      association study data set as a discovery sample, we obtained suggestive evidence
      of association with SNPs for several novel candidate genes. CONCLUSIONS: Some
      genes contribute to AD pathogenesis in both white and African American cohorts,
      although it is unclear whether the causal variants are the same. A larger African
      American sample will be needed to confirm novel gene associations, which may be
      population specific.

PMID- 22159058
TI  - Paraneoplastic syndrome of inappropriate antidiuretic hormone mimicking limbic
      encephalitis.
AB  - OBJECTIVE: To compare the features of paraneoplastic syndrome of inappropriate
      antidiuretic hormone with those of limbic encephalitis. DESIGN: Case study.
      SETTING: Academic medical center. PATIENT: A 46-year-old woman with progressive
      memory impairment, hyponatremia, and seizures. INTERVENTIONS: Magnetic resonance
      imaging of the brain, fluoro-2-deoxyglucose positron emission tomography of the
      body, and immunohistochemical analysis of a resected tumor. RESULTS: Though the
      patient presented with clinical features of classic limbic encephalitis, magnetic
      resonance imaging, electroencephalogram, and cerebrospinal fluid analysis
      findings were unremarkable. Her chronic hyponatremia was ultimately found to be
      due to ectopic secretion of antidiuretic hormone by a neuroendocrine tumor with
      Merkel cell carcinoma phenotype. CONCLUSIONS: Patients presenting with memory
      impairment, seizures, and hyponatremia should undergo a thorough workup for
      occult malignancy. In addition to considering classic immune-mediated
      paraneoplastic limbic encephalitis, the ectopic secretion of antidiuretic hormone
      should be included in the differential diagnosis.

PMID- 22159057
TI  - Propylthiouracil-induced lupus, antiphospholipid syndrome, and stroke in a
      patient with Graves hyperthyroidism.
AB  - OBJECTIVE: To describe a case of propylthiouracil-induced lupus, complicated with
      antiphospholipid syndrome and acute ischemic stroke. DESIGN: Case report.
      SETTING: Academic medical center. PATIENT: A 27-year-old man with a diagnosis of
      Graves disease developed multiple ischemic strokes 2 weeks after starting
      treatment with propylthiouracil. Thyrotoxicosis and abnormal hypercoagulable and
      rheumatological profiles were remarkable, with prolonged partial thromboplastin
      time, elevated anticardiolipin antibody level, and positive antinuclear antibody,
      lupus anticoagulant, Sjogren antibody, and anti-double-stranded DNA antibody test
      results, which were more than 8-fold greater than normal values. No clinical
      manifestations of systemic lupus erythematosus were present. INTERVENTION:
      Discontinuation of propylthiouracil and treatment with radioactive iodine.
      RESULTS: Hyperthyroidism resolved and anti-double-stranded DNA antibodies
      returned to normal levels. Eventually, antiphospholipid syndrome was diagnosed.
      He was treated with oral anticoagulation and remained asymptomatic for 1 year of
      follow-up. CONCLUSION: In this young man with Graves hyperthyroidism, treatment
      with propylthiouracil was associated with transient autoimmune reactions
      suggestive of drug-induced lupus, antiphospholipid syndrome, and acute ischemic
      stroke.

PMID- 22159059
TI  - Quantitative and qualitative analysis of ambulatory electroencephalography during
      mild traumatic brain injury.
AB  - OBJECTIVES: To characterize the neurophysiological changes in a patient with mild
      traumatic brain injury (mTBI) and to compare these changes with a small cohort of
      patients with neurocardiogenic syncope, an analogous cause of transient
      neurological dysfunction. DESIGN: Case report and quantitative analysis of a
      small electroencephalography (EEG) cohort. SETTING: University-affiliated
      teaching hospital. PATIENTS: A 64-year-old man with mTBI recorded on ambulatory
      EEG. The comparison group was 4 patients with spontaneous neurocardiogenic
      syncope during continuous video EEG recording. INTERVENTION: Quantitative and
      qualitative analysis of EEG. MAIN OUTCOME MEASURES: Changes in quantitative EEG
      measurements between the patient with mTBI and the comparison group. RESULTS: In
      the patient with mTBI, there was an abrupt decrease in high-frequency (beta)
      power and alpha-delta ratio immediately after the injury and a corresponding
      increase in lower-frequency (alpha, theta, delta) power. The change in beta power
      resolved within 5 minutes of the injury, but the increases in low-frequency power
      persisted up to 20 minutes after the injury before resolving. Similar but smaller
      changes were seen in the patients with syncope, but these changes resolved within
      5 minutes, with no intermediate or long-term changes. CONCLUSIONS: The
      quantitative EEG changes in mTBI are initially similar to those in syncope,
      suggesting acute transient cortical dysfunction. However, there are longer
      lasting increases in low-frequency power during mTBI, suggesting ongoing
      disruption of cortical-thalamic circuits.

PMID- 22159060
TI  - Exercise-associated numbness and tingling in the legs.
AB  - A 52-year-old physically active man with a medical history of coronary artery
      disease, hypertension, and hyperlipidemia presented with numbness and tingling in
      the legs. His symptoms were intermittent initially, triggered by running or
      playing soccer and relieved by rest. Symptoms progressed during 1 year. The
      numbness became more constant, and he developed leg pain radiating from the
      popliteal fossa to the heel bilaterally (pain was more severe in the left leg
      compared with the right leg). Recently, he had noted some constipation as well as
      difficulty in initiating urination.

PMID- 22159061
TI  - Recurrent embolic stroke due to nonbacterial thrombotic endocarditis followed by
      transesophageal echocardiography.

PMID- 22159062
TI  - Growing posterior fossa arachnoid cyst causing tonsillar herniation and
      hydrocephalus.

PMID- 22159063
TI  - Radiation-induced myelopathy: treatment with bevacizumab.

PMID- 22159064
TI  - Angioplasty for symptomatic middle cerebral artery stenosis and a perioperative
      evaluation using high-resolution magnetic resonance imaging at 3 T.

PMID- 22159065
TI  - Ultrastructural mitochondrial abnormalities in patients with sporadic amyotrophic
      lateral sclerosis.

PMID- 22159066
TI  - Central nervous system problems with eosinophilia.

PMID- 22159067
TI  - Reversible cerebral vasoconstriction syndrome and hemorrhagic events: who
      precedes whom?

PMID- 22159068
TI  - Parkinson disease and vitamin D: an interplay between genes and the environment?

PMID- 22159069
TI  - Optical materials based on molecular nanoparticles.
AB  - A major part of contemporary nanomaterials research is focused on metal and
      semiconductor nanoparticles, constituted of extended lattices of atoms or ions.
      Molecular nanoparticles assembled from small molecules through non-covalent
      interactions are relatively less explored but equally fascinating materials.
      Their unique and versatile characteristics have attracted considerable attention
      in recent years, establishing their identity and status as a novel class of
      nanomaterials. Optical characteristics of molecular nanoparticles capture the
      essence of their nanoscale features and form the basis of a variety of
      applications. This review describes the advances made in the field of fabrication
      of molecular nanoparticles, the wide spectrum of their optical and nonlinear
      optical characteristics and explorations of the potential applications that
      exploit their unique optical attributes.

PMID- 22159070
TI  - Alginate modified nanostructured calcium carbonate with enhanced delivery
      efficiency for gene and drug delivery.
AB  - To improve the performance of nanostructured calcium carbonate in gene delivery,
      a hydrophilic polysaccharide, alginate, was added to calcium carbonate co
      precipitation systems to form alginate/CaCO(3)/DNA nanoparticles. The size and
      zeta-potential of the nanoparticles were measured by a zetasizer. Due to the
      existence of alginate chains which retarded the growth of calcium carbonate based
      co-precipitates, the alginate/CaCO(3)/DNA nanoparticles exhibited a decreased
      size and enhanced stability in the aqueous solution. To evaluate the gene and
      drug co-delivery ability, doxorubicin hydrochloride (DOX), a water-soluble
      anticancer drug, was loaded in the nanoparticles to form alginate/CaCO(3)/DNA/DOX
      nanoparticles. The in vitro gene transfections mediated by different
      nanoparticles in 293 T cells and HeLa cells were carried out, using pGL3-Luc as a
      reporter plasmid. With an appropriate amount of alginate, the gene transfection
      efficiency of alginate modified nanoparticles could be significantly enhanced as
      compared with the nanoparticles without alginate modification for the gene
      delivery systems, as well as the gene and drug co-delivery systems. The study on
      in vitro cell inhibition effects showed that the cell viability decreased with
      increasing DOX amount loaded in alginate/CaCO(3)/DNA/DOX nanoparticles. The
      alginate modification is a useful strategy to improve the calcium carbonate co
      precipitation technique for the preparation of gene and drug delivery systems,
      and the nanoparticles prepared in this study have promising applications in gene
      and drug delivery.

PMID- 22159071
TI  - Regulating cell differentiation at different layers.

PMID- 22159072
TI  - Retraction: Take-over: multiple mechanisms of inter-adipocyte communication.

PMID- 22159073
TI  - Exposure to inhalable dust and endotoxin among Danish livestock farmers: results
      from the SUS cohort study.
AB  - Studies on personal dust and endotoxin concentrations among animal farmers have
      been either small or limited to a few sectors in their investigations. The
      present study aimed to provide comparable information on the levels and
      variability of exposure to personal dust and endotoxin in different types of
      animal farmers. 507 personal inhalable dust samples were collected from 327
      farmers employed in 54 pig, 26 dairy, 3 poultry, and 3 mink farms in Denmark.
      Measurements in pig and dairy farmers were full-shift and performed during summer
      and winter, while poultry and mink farmers were monitored during 4 well-defined
      production stages. The collected samples were measured for dust gravimetrically
      and analyzed for endotoxin by the Limulus amebocyte lysate assay. Simple
      statistics and random-effect analysis were used to describe the levels and the
      variability in measured dust and endotoxin exposure concentrations. Measured
      inhalable dust levels had an overall geometric mean of 2.5 mg m(-3) (range <LOD
      to 47.8) and endotoxin of 988 EU m(-3) (range <LOD to 374,000). The highest dust
      and endotoxin concentrations were measured among pig and poultry farmers, and
      were the lowest among dairy and mink farmers, respectively. Exposure among pig
      and cattle farmers was characterised by a substantial day-to-day variability that
      increased from the indoor to outdoor working environment. Only mink farmers
      complied with the Danish occupational exposure limit for total dust (3 mg m(-3)).
      More than 93% of our measurements exceeded the recently proposed Dutch exposure
      limit for endotoxin (90 EU m(-3)). These findings suggest animal farmers to be
      exposed to high levels of dust and endotoxin consistent with an increased risk of
      developing respiratory symptoms and diseases. The development of preventive
      strategies to reduce exposure will require in-depth identification of factors
      that affect day-to-day variability in exposure.

PMID- 22159074
TI  - The magnetic coupling in manganese-based dinuclear superhalogens and their
      analogues. A theoretical characterization from a combined DFT and BS study.
AB  - The structures, relative stabilities, vertical detachment energies and magnetic
      coupling properties of a series of manganese-based dinuclear superhalogens and
      their isoelectronic analogues are explored via a combined density functional
      theory and broken symmetry study. Both the capabilities of various exchange
      correlation functionals and basis set effects are investigated. The large
      magnitudes of the calculated exchange coupling constants indicate clearly the
      apparent molecular magnetism of these new types of superhalogen. Encouragingly,
      the high possibility of the coexistence of both high stability and strong
      magnetic coupling in these new polynuclear superhalogens is also confirmed.
      Besides these, the larger magnitudes of the calculated coupling constants of iron
      based clusters here, compared with the homodinuclear [Mn(2)Cl(5)](-) cluster,
      demonstrate the possibility of the existence of strong magnetic coupling in
      potential iron-based homo- and heterodinuclear superhalogens. The analysis of
      spin density distribution is also performed in order to understand the coupling
      mechanisms.

PMID- 22159075
TI  - The electric field as a novel switch for uptake/release of hydrogen for storage
      in nitrogen doped graphene.
AB  - Nitrogen-doped graphene was recently synthesized and was reported to be a
      catalyst for hydrogen dissociative adsorption under a perpendicular applied
      electric field (F). In this work, the diffusion of H atoms on N-doped graphene,
      in the presence and absence of an applied perpendicular electric field, is
      studied using density functional theory. We demonstrate that the applied field
      can significantly facilitate the binding of hydrogen molecules on N-doped
      graphene through dissociative adsorption and diffusion on the surface. By
      removing the applied field the absorbed H atoms can be released efficiently. Our
      theoretical calculation indicates that N-doped graphene is a promising hydrogen
      storage material with reversible hydrogen adsorption/desorption where the applied
      electric field can act as a switch for the uptake/release processes.

PMID- 22159076
TI  - Multi component self-assembly: supramolecular organic frameworks containing metal
      rotaxane subunits (RSOFs).
AB  - A facile, one-pot synthesis of rotaxanated supramolecular organic frameworks
      (RSOFs) is reported. These systems consist of bis-carboxylate anions threaded
      through the core of tetraimidazolium macrocycles. Trivalent metal cations,
      yttrium(III) and smaller lanthanides, are used to "lock" the threaded strut in
      place. This results in the formation of three-dimensional RSOFs.

PMID- 22159077
TI  - Processing and stability of type IIc sodium-dependent phosphate cotransporter
      mutations in patients with hereditary hypophosphatemic rickets with
      hypercalciuria.
AB  - Mutations in the apically located Na(+)-dependent phosphate (NaPi) cotransporter,
      SLC34A3 (NaPi-IIc), are a cause of hereditary hypophosphatemic rickets with
      hypercalciuria (HHRH). We have characterized the impact of several HHRH mutations
      on the processing and stability of human NaPi-IIc. Mutations S138F, G196R, R468W,
      R564C, and c.228delC in human NaPi-IIc significantly decreased the levels of NaPi
      cotransport activities in Xenopus oocytes. In S138F and R564C mutant proteins,
      this reduction is a result of a decrease in the V(max) for P(i), but not the
      K(m). G196R, R468W, and c.228delC mutants were not localized to oocyte membranes.
      In opossum kidney (OK) cells, cell surface labeling, microscopic confocal
      imaging, and pulse-chase experiments showed that G196R and R468W mutations
      resulted in an absence of cell surface expression owing to endoplasmic reticulum
      (ER) retention. G196R and R468W mutants could be partially stabilized by low
      temperature. In blue native-polyacrylamide gel electrophoresis analysis, G196R
      and R468W mutants were either denatured or present in an aggregation complex. In
      contrast, S138F and R564C mutants were trafficked to the cell surface, but more
      rapidly degraded than WT protein. The c.228delC mutant did not affect endogenous
      NaPi uptake in OK cells. Thus, G196R and R468W mutations cause ER retention,
      while S138F and R564C mutations stimulate degradation of human NaPi-IIc in renal
      epithelial cells. Together, these data suggest that the NaPi-IIc mutants in HHRH
      show defective processing and stability.

PMID- 22159079
TI  - Diabetes alters subsets of endothelial progenitor cells that reside in blood,
      bone marrow, and spleen.
AB  - Circulating endothelial progenitor cells (EPCs) derived from the bone marrow (BM)
      participate in maintaining endothelial integrity and vascular homeostasis.
      Reduced EPC number and function result in vascular complications in diabetes.
      EPCs are a population of cells existing in various differentiation stages, and
      their cell surface marker profiles change during the process of mobilization and
      maturation. Hence, a generally accepted marker combination and a standardized
      protocol for the quantification of EPCs remain to be established. To determine
      the EPC subsets that are affected by diabetes, we comprehensively analyzed 32
      surface marker combinations of mouse peripheral blood (PB), BM, and spleen cells
      by multicolor flow cytometry. Ten subsets equivalent to previously reported mouse
      EPCs significantly declined in number in the PB of streptozotocin-induced
      diabetic mice, and this reduction was reversed by insulin treatment. The PI(
      )Lin(-)c-Kit(-)Sca-1(+)Flk-1(-)CD34(-)CD31(+) EPC cluster, which can
      differentiate into mature endothelial cells in vitro, was the highest population
      in the PB, BM, and spleen and occurred 61 times more in the spleen than in the
      PB. The cell number significantly decreased in the BM as well as in the PB but
      paradoxically increased in the spleen under diabetic conditions. Insulin
      treatment reversed the decrease of EPC subsets in the BM and PB and reversed
      their increase in spleen. A similar tendency was observed in some of the major
      cell populations in db/db mice. To the best of our knowledge, we are the first to
      report spatial population changes in mouse EPCs by diabetes in the blood and in
      the BM across the spleen. Diminished circulating EPC supply by diabetes may be
      ascribed to impaired EPC production in the BM and to decreased EPC mobilization
      from the spleen, which may contribute to vascular dysfunction in diabetic
      conditions.

PMID- 22159078
TI  - Laminin-alpha1 LG4-5 domain binding to dystroglycan mediates muscle cell
      survival, growth, and the AP-1 and NF-kappaB transcription factors but also has
      adverse effects.
AB  - In our previous studies, we showed laminin binds alpha-dystroglycan in the
      dystrophin glycoprotein complex and initiates cell signaling pathways. Here,
      differentiated C2C12 myocytes serve as a model of skeletal muscle. C2C12 cells
      have a biphasic response to the laminin-alpha(1) laminin globular (LG) 4-5
      domains (1E3) dependent on the concentration used; at low concentrations of 1E3
      (<1 MUg/ml), myoblast proliferation is increased while higher concentrations (>1
      MUg/ml) cause apoptosis in myoblasts and differentiated myotubes. This alters the
      activation of the transcription factors activator protein-1 (AP-1) and NF-kappaB
      via laminin-dystrophin glycoprotein complex (DGC)-src-grb2-sos1-Rac1-Pak1-c-jun N
      terminal kinase (JNK)p46 and laminin-DGC-Gbetagamma-phosphatidylinositol 3-kinase
      (PI3K)-Akt pathways, respectively. A specific antibody against Ser(63)
      phosphorylated c-jun completely blocks or supershifts the AP-1-DNA binding
      resulting from laminin binding but only partially blocks or supershifts the AP-1
      DNA binding resulting from 1E3. This suggests that AP-1 contains phosphorylated c
      jun in the presence of hololaminin but contains a different composition in the
      presence of 1E3. Nuclear NF-kappaB was only upregulated by a low concentration of
      1E3 and is then diminished by a higher concentration; it also has a biphasic
      response. Nuclear localization of NF-kappaB is affected by PI3K/Akt signaling,
      and DGC associated PI3K activity also shows a biphasic response to 1E3.
      Furthermore, our data suggest that activation of c-jun N-terminal kinase
      participates in the cell survival pathway and suggest that NF-kappaB is involved
      in both survival and cell death. A model is presented which incorporates these
      observations.

PMID- 22159080
TI  - Euryhaline pufferfish NBCe1 differs from nonmarine species NBCe1 physiology.
AB  - Marine fish drink seawater and eliminate excess salt by active salt transport
      across gill and gut epithelia. Euryhaline pufferfish (Takifugu obscurus, mefugu)
      forms a CaCO(3) precipitate on the luminal gut surface after transitioning to
      seawater. NBCe1 (Slc4a4) at the basolateral membrane of intestinal epithelial
      cell plays a major role in transepithelial intestinal HCO(3)(-) secretion and is
      critical for mefugu acclimation to seawater. We assayed fugu-NBCe1 (fNBCe1)
      activity in the Xenopus oocyte expression system. Similar to NBCe1 found in other
      species, fNBCe1 is an electrogenic Na(+)/HCO(3)(-) cotransporter and sensitive to
      the stilbene inhibitor DIDS. However, our experiments revealed several unique and
      distinguishable fNBCe1 transport characteristics not found in mammalian or other
      teleost NBCe1-orthologs: electrogenic Li(+)/nHCO(3)(-) cotransport; HCO(3)(-)
      independent, DIDS-insensitive transport; and increased basal intracellular Na(+)
      accumulation. fNBCe1 is a voltage-dependent Na(+)/nHCO(3)(-) cotransporter that
      rectifies, independently from the extracellular Na(+) or HCO(3)(-) concentration,
      around -60 mV. Na(+) removal (0Na(+) prepulse) is necessary to produce the true
      HCO(3)(-)-elicited current. HCO(3)(-) addition results in huge outward currents
      with quick current decay. Kinetic analysis of HCO(3)(-) currents reveals that
      fNBCe1 has a much higher transport capacity (higher maximum current) and lower
      affinity (higher K(m)) than human kidney NBCe1 (hkNBCe1) does in the
      physiological range (membrane potential = -80 mV; [HCO(3)(-)] = 10 mM). In this
      state, fNBCe1 is in favor of operating as transepithelial HCO(3)(-) secretion,
      opposite of hkNBCe1, from blood to the luminal side. Thus, fugu-NBCe1 represents
      the first ortholog-based tool to study amino acid substitutions in NBCe1 and how
      those change ion and voltage dependence.

PMID- 22159081
TI  - Arrestins 2 and 3 differentially regulate ETA and P2Y2 receptor-mediated cell
      signaling and migration in arterial smooth muscle.
AB  - Overstimulation of endothelin type A (ET(A)) and nucleotide (P2Y) Galpha(q)
      coupled receptors in vascular smooth muscle causes vasoconstriction,
      hypertension, and, eventually, hypertrophy and vascular occlusion. G protein
      coupled receptor kinases (GRKs) and arrestin proteins are sequentially recruited
      by agonist-occupied Galpha(q)-coupled receptors to terminate phospholipase C
      signaling, preventing prolonged/inappropriate contractile signaling. However,
      these proteins also play roles in the regulation of several mitogen-activated
      protein kinase (MAPK) signaling cascades known to be essential for vascular
      remodeling. Here we investigated whether different arrestin isoforms regulate
      endothelin and nucleotide receptor MAPK signaling in rat aortic smooth muscle
      cells (ASMCs). When intracellular Ca(2+) levels were assessed in isolated ASMCs
      loaded with Ca(2+)-sensitive dyes, P2Y(2) and ET(A) receptor desensitization was
      attenuated by selective small-interfering (si)RNA-mediated depletion of G protein
      coupled receptor kinase 2 (GRK2). Using similar siRNA techniques, knockdown of
      arrestin2 prevented P2Y(2) receptor desensitization and enhanced and prolonged
      p38 and ERK MAPK signals, while arrestin3 depletion was ineffective. Conversely,
      arrestin3 knockdown prevented ET(A) receptor desensitization and attenuated ET1
      stimulated p38 and ERK signals, while arrestin2 depletion had no effect. Using
      Transwell assays to assess agonist-stimulated ASMC migration, we found that UTP
      stimulated migration was markedly attenuated following arrestin2 depletion, while
      ET1-stimulated migration was attenuated following knockdown of either arrestin.
      These data highlight a differential arrestin-dependent regulation of ET(A) and
      P2Y(2) receptor-stimulated MAPK signaling. GRK2 and arrestin expression are
      essential for agonist-stimulated ASMC migration, which, as a key process in
      vascular remodeling, highlights the potential roles of GRK2 and arrestin proteins
      in the progression of vascular disease.

PMID- 22159082
TI  - Bridging the gap between structure and kinetics of human SGLT1.
AB  - The Na(+)-glucose cotransporter hSGLT1 is a member of a class of membrane
      proteins that harness Na(+) electrochemical gradients to drive uphill solute
      transport. Although hSGLT1 belongs to one gene family (SLC5), recent structural
      studies of bacterial Na(+) cotransporters have shown that Na(+) transporters in
      different gene families have the same structural fold. We have constructed
      homology models of hSGLT1 in two conformations, the inward-facing occluded (based
      on vSGLT) and the outward open conformations (based on Mhp1), mutated in turn
      each of the conserved gates and ligand binding residues, expressed the SGLT1
      mutants in Xenopus oocytes, and determined the functional consequences using
      biophysical and biochemical assays. The results establish that mutating the
      ligand binding residues produces profound changes in the ligand affinity (the
      half-saturation concentration, K(0.5)); e.g., mutating sugar binding residues
      increases the glucose K(0.5) by up to three orders of magnitude. Mutation of the
      external gate residues increases the Na(+) to sugar transport stoichiometry,
      demonstrating that these residues are critical for efficient cotransport. The
      changes in phlorizin inhibition constant (K(i)) are proportional to the changes
      in sugar K(0.5), except in the case of F101C, where phlorizin K(i) increases by
      orders of magnitude without a change in glucose K(0.5). We conclude that glucose
      and phlorizin occupy the same binding site and that F101 is involved in binding
      to the phloretin group of the inhibitor. Substituted-cysteine accessibility
      methods show that the cysteine residues at the position of the gates and sugar
      binding site are largely accessible only to external hydrophilic
      methanethiosulfonate reagents in the presence of external Na(+), demonstrating
      that the external sugar (and phlorizin) binding vestibule is opened by the
      presence of external Na(+) and closes after the binding of sugar and phlorizin.
      Overall, the present results provide a bridge between kinetics and structural
      studies of cotransporters.

PMID- 22159083
TI  - Nongenomic STAT5-dependent effects on Golgi apparatus and endoplasmic reticulum
      structure and function.
AB  - We report unexpected nongenomic functions of signal transducer and activator of
      transcription (STAT) 5 species in the cytoplasm aimed at preserving the structure
      and function of the Golgi apparatus and rough endoplasmic reticulum (ER) in
      vascular cells. Immunoimaging and green fluorescent protein-tagged-STAT5a protein
      localization studies showed the constitutive association of nonphosphorylated
      STAT5a, and to a lesser extent STAT5b, with the Golgi apparatus and of STAT5a
      with centrosomes in human pulmonary arterial endothelial and smooth muscle cells.
      Acute knockdown of STAT5a/b species using small interfering RNAs (siRNAs),
      including in the presence of an mRNA synthesis inhibitor (5,6-dichloro-1-beta-d
      ribofuranosylbenzimidazole), produced a dramatic phenotype within 1 day,
      consisting of dilatation and fragmentation of Golgi cisternae, a marked tubule-to
      cyst change in the ER, increased accumulation of reticulon-4 (RTN4)/Nogo-B and
      atlastin-3 (ATL3) at cyst-zone boundaries, cystic separation of the outer and
      inner nuclear membranes, accompanied by scalloped/lunate distortion of the
      nucleus, with accumulation of RTN4 on convex sides of distorted nuclei. These
      cells showed inhibition of vesicular stomatitis virus G protein glycoprotein
      trafficking, mitochondrial fragmentation, and reduced mitochondrial function.
      STAT5a/b(-/-) mouse embryo fibroblasts also showed altered ER/Golgi dynamics.
      RTN4 knockdown using siRNA did not affect development of the cystic phenotype;
      ATL3 siRNA led to effacement of cyst-zone boundaries. In magnetic-bead cross
      immunopanning assays, ATL3 bound both STAT5a and STAT5b. Remarkably, this novel
      cystic ER/lunate nucleus phenotype was characteristic of vascular cells in
      arterial lesions of idiopathic pulmonary hypertension, an unrelentingly fatal
      human disease. These data provide evidence of a STAT-family protein regulating
      the structure of a cytoplasmic organelle and implicate this mechanism in the
      pathogenesis of a human disease.

PMID- 22159084
TI  - Role of N-glycosylation in cell surface expression and protection against
      proteolysis of the intestinal anion exchanger SLC26A3.
AB  - SLC26A3 is a Cl(-)/HCO(3)(-) exchanger that plays a major role in Cl(-)
      absorption from the intestine. Its mutation causes congenital chloride-losing
      diarrhea. It has been shown that SLC26A3 are glycosylated, with the attached
      carbohydrate being extracellular and perhaps modulating function. However, the
      role of glycosylation has yet to be clearly determined. We used the approaches of
      biochemical modification and site-directed mutagenesis to prevent glycosylation.
      Deglycosylation experiments with glycosidases indicated that the mature
      glycosylated form of SLC26A3 exists at the plasma membrane, and a putative large
      second extracellular loop contains all of the N-linked carbohydrates.
      Deglycosylation of SLC26A3 causes depression of transport activity compared with
      wild-type, although robust intracellular pH changes were still observed,
      suggesting that N-glycosylation is not absolutely necessary for transport
      activity. To localize glycosylation sites, we mutated the five consensus sites by
      replacing asparagine (N) with glutamine. Immnoblotting suggests that SLC26A3 is
      glycosylated at N153, N161, and N165. Deglycosylation of SLC26A3 causes a defect
      in cell surface processing with decreased cell surface expression. We also
      assessed whether SLC26A3 is protected from tryptic digestion. While the mature
      glycosylated SLC26A3 showed little breakdown after treatment with trypsin,
      deglycosylated SLC26A3 exhibited increased susceptibility to trypsin, suggesting
      that the oligosaccharides protect SLC26A3 from tryptic digestion. In conclusion,
      our data indicate that N-glycosylation of SLC26A3 is important for cell surface
      expression and for protection from proteolytic degradation that may contribute to
      the understanding of pathogenesis of congenital disorders of glycosylation.

PMID- 22159085
TI  - Differential N termini in epithelial Na+ channel delta-subunit isoforms modulate
      channel trafficking to the membrane.
AB  - The epithelial Na(+) channel (ENaC) is a heteromultimeric ion channel that plays
      a key role in Na(+) reabsorption across tight epithelia. The canonical ENaC is
      formed by three analogous subunits, alpha, beta, and gamma. A fourth ENaC
      subunit, named delta, is expressed in the nervous system of primates, where its
      role is unknown. The human delta-ENaC gene generates at least two splice
      isoforms, delta(1) and delta(2) , differing in the N-terminal sequence. Neurons
      in diverse areas of the human and monkey brain differentially express either
      delta(1) or delta(2) , with few cells coexpressing both isoforms, which suggests
      that they may play specific physiological roles. Here we show that heterologous
      expression of delta(1) in Xenopus oocytes and HEK293 cells produces higher
      current levels than delta(2) . Patch-clamp experiments showed no differences in
      single channel current magnitude and open probability between isoforms. Steady
      state plasma membrane abundance accounts for the dissimilarity in macroscopic
      current levels. Differential trafficking between isoforms is independent of beta-
      and gamma-subunits, PY-motif-mediated endocytosis, or the presence of additional
      lysine residues in delta(2)-N terminus. Analysis of delta(2)-N terminus
      identified two sequences that independently reduce channel abundance in the
      plasma membrane. The delta(1) higher abundance is consistent with an increased
      insertion rate into the membrane, since endocytosis rates of both isoforms are
      indistinguishable. Finally, we conclude that delta-ENaC undergoes dynamin
      independent endocytosis as opposed to alphabetagamma-channels.

PMID- 22159086
TI  - Elevated ammonium levels: differential acute effects on three glutamate
      transporter isoforms.
AB  - Increased ammonium (NH(4)(+)/NH(3)) in the brain is a significant factor in the
      pathophysiology of hepatic encephalopathy, which involves altered glutamatergic
      neurotransmission. In glial cell cultures and brain slices, glutamate uptake
      either decreases or increases following acute ammonium exposure but the factors
      responsible for the opposing effects are unknown. Excitatory amino acid
      transporter isoforms EAAT1, EAAT2, and EAAT3 were expressed in Xenopus oocytes to
      study effects of ammonium exposure on their individual function. Ammonium
      increased EAAT1- and EAAT3-mediated [(3)H]glutamate uptake and glutamate
      transport currents but had no effect on EAAT2. The maximal EAAT3-mediated
      glutamate transport current was increased but the apparent affinities for
      glutamate and Na(+) were unaltered. Ammonium did not affect EAAT3-mediated
      transient currents, indicating that EAAT3 surface expression was not enhanced.
      The ammonium-induced stimulation of EAAT3 increased with increasing extracellular
      pH, suggesting that the gaseous form NH(3) mediates the effect. An ammonium
      induced intracellular alkalinization was excluded as the cause of the enhanced
      EAAT3 activity because 1) ammonium acidified the oocyte cytoplasm, 2)
      intracellular pH buffering with MOPS did not reduce the stimulation, and 3)
      ammonium enhanced pH-independent cysteine transport. Our data suggest that the
      ammonium-elicited uptake stimulation is not caused by intracellular
      alkalinization or changes in the concentrations of cotransported ions but may be
      due to a direct effect on EAAT1/EAAT3. We predict that EAAT isoform-specific
      effects of ammonium combined with cell-specific differences in EAAT isoform
      expression may explain the conflicting reports on ammonium-induced changes in
      glial glutamate uptake.

PMID- 22159087
TI  - Maxi-channels recorded in situ from ICC and pericytes associated with the mouse
      myenteric plexus.
AB  - Ion channels are fundamental to gastrointestinal pacemaking by interstitial cells
      of Cajal (ICC). Previously, we have recorded a high-conductance chloride channel
      (HCCC) from ICC, both in culture and in situ, associated with the myenteric
      plexus. The biophysical properties of the HCCC (conductance, subconductances,
      voltage- and time-dependent inactivation) suggest it is a member of a class
      called the maxi-anion channels. In this study we further investigated the
      properties of the HCCC in situ. Our main finding was that the HCCC is not
      strictly a chloride channel but has a relative sodium-chloride permeability
      (P(Na/Cl)) of 0.76 to 1.64 (depending on the method of measurement). Therefore,
      we have renamed the HCCC the "maxi-channel." A maxi-channel was also expressed by
      pericytes associated with the vasculature near the myenteric plexus. This had a
      lower P(Na/Cl) (0.33 to 0.49, depending on the method of measurement) but similar
      conductance (326 +/- 7 vs. 316 +/- 24 pS for ICC). This is the first report of
      cation permeability equaling anion permeability in a maxi-anion channel. As such,
      the properties of the maxi-channels described in this article may have
      implications for the maxi-anion channel field, as well as for studies of their
      role in ICC and pericytes.

PMID- 22159088
TI  - Thrombin-induced ATP release from human umbilical vein endothelial cells.
AB  - ATP and its degradation products play an important role as signaling molecules in
      the vascular system, and endothelial cells are considered to be an important
      source of nucleotide release. To investigate the mechanism and physiological
      significance of endothelial ATP release, we compared different pharmacological
      stimuli for their ability to evoke ATP release from first passage cultivated
      human umbilical vein endothelial cells (HUVECs). Agonists known to increase
      intracellular Ca(2+) levels (A23187, histamine, thrombin) induced a stable, non
      lytic ATP release. Since thrombin proved to be the most robust and reproducible
      stimulus, the molecular mechanism of thrombin-mediated ATP release from HUVECs
      was further investigated. ATP rapidly increased with thrombin (1 U/ml) and
      reached a steady-state level after 4 min. Loading the cells with BAPTA-AM to
      capture intracellular calcium suppressed ATP release. The thrombin-specific,
      protease-activated receptor 1 (PAR-1)-specific agonist peptide TFLLRN (10 MUM)
      fully mimicked thrombin action on ATP release. To identify the nature of the ATP
      permeable pathway, we tested various inhibitors of potential ATP channels for
      their ability to inhibit the thrombin response. Carbenoxolone, an inhibitor of
      connexin hemichannels and pannexin channels, as well as Gd(3+) were highly
      effective in blocking the thrombin-mediated ATP release. Specifically targeting
      connexin43 (Cx43) and pannexin1 (Panx1) revealed that reducing Panx1 expression
      significantly reduced ATP release, while downregulating Cx43 was ineffective. Our
      study demonstrates that thrombin at physiological concentrations is a potent
      stimulus of endothelial ATP release involving PAR-1 receptor activation and
      intracellular calcium mobilization. ATP is released by a carbenoxolone- and
      Gd(3+)- sensitive pathway, most likely involving Panx1 channels.

PMID- 22159089
TI  - Double N-H bond activation of N,N'-bis-substituted hydrazines with stable N
      heterocyclic silylene.
AB  - The reaction of N-heterocyclic silylene (NHSi) L [L = CH{(C[double bond, length
      as m-dash]CH(2))(CMe)(2,6-iPr(2)C(6)H(3)N)(2)}Si] with benzoylhydrazine, 1,2
      dicarbethoxyhydrazine, 1,2-diacetylhydrazine and 1,2-bis(tert
      butoxycarbonyl)hydrazine in 1 : 1 molar ratio resulted in compounds 1-4 with an
      almost quantitative yield and five coordinate silicon atoms. Compounds 1-4 were
      formed by double N-H bond activation by deliberate selection of N,N'-bis
      substituted hydrazine compounds bearing the -C(O)NHNH- unit. Compounds 1-4 were
      characterized by NMR spectroscopy, EI-MS and elemental analysis. The molecular
      structures of compounds 1-3 were unambiguously established by single crystal X
      ray structural analysis.

PMID- 22159090
TI  - Syntheses, structures, and magnetic characterizations of cyanide-bridged
      Fe(III)Mn(III) chains constructed by mer-Fe(III)tricyanide and Mn(III) Schiff
      bases: magnetostructural relationship.
AB  - Five Fe(III)Mn(III) bimetallic compounds [Fe(iqc)(CN)(3)][Mn(5
      Xsalen)].pMeOH.qMeCN.rH(2)O [Hiqc = N-(quinolin-8-yl)isoquinoline-1-carboxamide;
      salen = N,N'-ethylenebis(salicylideneiminato) dianion; X = H(2), F(3, 3a), Cl(4),
      Br(5)] were prepared by assembling a newly designed mer-Fe tricyanide
      (Ph(4)P)[Fe(iqc)(CN)(3)].0.5H(2)O (1) and the respective Mn Schiff bases Mn(5
      Xsalen)(+). Compounds 2-4 show linear chain structures in which trans-positioned
      cyanides of the Fe precursor bridge neighbouring Mn atoms, while 5 is a zigzag
      chain coordination polymer where two cyanide groups of the precursor in the cis
      mode act as bridges. The structural change from linear to zigzag may arise from
      the size effect of the halogens. The reversible structural transformation occurs
      between 3 and 3a upon the solvation-desolvation protocol and the corresponding
      magnetic behaviours are affected. Furthermore, in 4 and 5, the helical chains are
      established through hydrogen bonding of solvent molecules. From a
      magnetostructural point of view, within the linear chain system, the
      ferromagnetic coupling in 2, contrary to antiferromagnetic interactions in 3-4,
      is associated with the large torsion angle of C(eq)-Fe-Mn-N(O)(eq) (eq =
      equatorial) as well as almost the linear Mn-N=C angle.

PMID- 22159091
TI  - The role of gap junctions in Charcot-Marie-Tooth disease.

PMID- 22159092
TI  - Molecular switches in the development and fate specification of vomeronasal
      neurons.

PMID- 22159093
TI  - Decrease in calcium concentration triggers neuronal retinoic acid synthesis
      during homeostatic synaptic plasticity.
AB  - Blockade of synaptic activity induces homeostatic plasticity, in part by
      stimulating synthesis of all-trans retinoic acid (RA), which in turn increases
      AMPA receptor synthesis. However, the synaptic signal that triggers RA synthesis
      remained unknown. Using multiple activity-blockade protocols that induce
      homeostatic synaptic plasticity, here we show that RA synthesis is activated
      whenever postsynaptic Ca(2+) entry is significantly decreased and that RA is
      required for upregulation of synaptic strength under these homeostatic plasticity
      conditions, suggesting that Ca(2+) plays an inhibitory role in RA synthesis.
      Consistent with this notion, we demonstrate that both transient Ca(2+) depletion
      by membrane-permeable Ca(2+) chelators and chronic blockage of L-type Ca(2+)
      channels induces RA synthesis. Moreover, the source of dendritic Ca(2+) entry
      that regulates RA synthesis is not specific because mild depolarization with KCl
      is sufficient to reverse synaptic scaling induced by L-type Ca(2+)-channel
      blocker. By expression of a dihydropyridine-insensitive L-type Ca(2+) channel, we
      further show that RA acts cell autonomously to modulate synaptic transmission.
      Our findings suggest that, in synaptically active neurons, modest "basal" levels
      of postsynaptic Ca(2+) physiologically suppress RA synthesis, whereas in
      synaptically inactive neurons, decreases in the resting Ca(2+) levels induce
      homeostatic plasticity by stimulating synthesis of RA that then acts in a cell
      autonomous manner to increase AMPA receptor function.

PMID- 22159094
TI  - Encoding of both positive and negative reward prediction errors by neurons of the
      primate lateral prefrontal cortex and caudate nucleus.
AB  - Learning can be motivated by unanticipated success or unexpected failure. The
      former encourages us to repeat an action or activity, whereas the latter leads us
      to find an alternative strategy. Understanding the neural representation of these
      unexpected events is therefore critical to elucidate learning-related circuits.
      We examined the activity of neurons in the lateral prefrontal cortex (PFC) and
      caudate nucleus of monkeys as they performed a trial-and-error learning task.
      Unexpected outcomes were widely represented in both structures, and neurons
      driven by unexpectedly negative outcomes were as frequent as those activated by
      unexpectedly positive outcomes. Moreover, both positive and negative reward
      prediction errors (RPEs) were represented primarily by increases in firing rate,
      unlike the manner in which dopamine neurons have been observed to reflect these
      values. Interestingly, positive RPEs tended to appear with shorter latency than
      negative RPEs, perhaps reflecting the mechanism of their generation. Last, in the
      PFC but not the caudate, trial-by-trial variations in outcome-related activity
      were linked to the animals' subsequent behavioral decisions. More broadly, the
      robustness of RPE signaling by these neurons suggests that actor-critic models of
      reinforcement learning in which the PFC and particularly the caudate are
      considered primarily to be "actors" rather than "critics," should be reconsidered
      to include a prominent evaluative role for these structures.

PMID- 22159095
TI  - Chondroitinase ABC combined with neurotrophin NT-3 secretion and NR2D expression
      promotes axonal plasticity and functional recovery in rats with lateral
      hemisection of the spinal cord.
AB  - Elevating spinal levels of neurotrophin NT-3 (NT3) while increasing expression of
      the NR2D subunit of the NMDA receptor using a HSV viral construct promotes
      formation of novel multisynaptic projections from lateral white matter (LWM)
      axons to motoneurons in neonates. However, this treatment is ineffective after
      postnatal day 10. Because chondroitinase ABC (ChABC) treatment restores
      plasticity in the adult CNS, we have added ChABC to this treatment and applied
      the combination to adult rats receiving a left lateral hemisection (Hx) at T8.
      All hemisected animals initially dragged the ipsilateral hindpaw and displayed
      abnormal gait. Rats treated with ChABC or NT3/HSV-NR2D recovered partial hindlimb
      locomotor function, but animals receiving combined therapy displayed the most
      improved body stability and interlimb coordination [Basso-Beattie-Bresnahan (BBB)
      locomotor scale and gait analysis]. Electrical stimulation of the left LWM at T6
      did not evoke any synaptic response in ipsilateral L5 motoneurons of control
      hemisected animals, indicating interruption of the white matter. Only animals
      with the full combination treatment recovered consistent multisynaptic responses
      in these motoneurons indicating formation of a detour pathway around the Hx.
      These physiological findings were supported by the observation of increased
      branching of both cut and intact LWM axons into the gray matter near the injury.
      ChABC-treated animals displayed more sprouting than control animals and those
      receiving NT3/HSV-NR2D; animals receiving the combination of all three treatments
      showed the most sprouting. Our results indicate that therapies aimed at
      increasing plasticity, promoting axon growth and modulating synaptic function
      have synergistic effects and promote better functional recovery than if applied
      individually.

PMID- 22159097
TI  - Stimulus-specific adaptation: can it be a neural correlate of behavioral
      habituation?
AB  - Habituation is the most basic form of learning, yet many gaps remain in our
      understanding of its underlying neural mechanisms. We demonstrate that in the
      owl's optic tectum (OT), a single, low-level, relatively short auditory stimulus
      is sufficient to induce a significant reduction in the neural response to a
      stimulus presented up to 60 s later. This type of neural adaptation was absent in
      neurons from the central nucleus of the inferior colliculus and from the auditory
      thalamus; however, it was apparent in the OT and the forebrain entopallium. By
      presenting sequences that alternate between two different auditory stimuli, we
      show that this long-lasting adaptation is stimulus specific. The response to an
      odd stimulus in the sequence was not smaller than the response to the same
      stimulus when it was first in the sequence. Finally, we measured the habituation
      of reflexive eye movements and show that the behavioral habituation is correlated
      with the neural adaptation. The finding of a long-lasting specific adaptation in
      areas related to the gaze control system and not elsewhere suggests its
      involvement in habituation processes and opens new directions for research on
      mechanisms of habituation.

PMID- 22159096
TI  - Epigenetic enhancement of BDNF signaling rescues synaptic plasticity in aging.
AB  - Aging-related cognitive declines are well documented in humans and animal models.
      Yet the synaptic and molecular mechanisms responsible for cognitive aging are not
      well understood. Here we demonstrated age-dependent deficits in long-term
      synaptic plasticity and loss of dendritic spines in the hippocampus of aged
      Fisher 344 rats, which were closely associated with reduced histone acetylation,
      upregulation of histone deacetylase (HDAC) 2, and decreased expression of a
      histone acetyltransferase. Further analysis showed that one of the key genes
      affected by such changes was the brain-derived neurotrophic factor (Bdnf) gene.
      Age-dependent reductions in H3 and H4 acetylation were detected within multiple
      promoter regions of the Bdnf gene, leading to a significant decrease in BDNF
      expression and impairment of downstream signaling in the aged hippocampus. These
      synaptic and signaling deficits could be rescued by enhancing BDNF and trkB
      expression via HDAC inhibition or by directly activating trkB receptors with 7,8
      dihydroxyflavone, a newly identified, selective agonist for trkB. Together, our
      findings suggest that age-dependent declines in chromatin histone acetylation and
      the resulting changes in BDNF expression and signaling are key mechanisms
      underlying the deterioration of synaptic function and structure in the aging
      brain. Furthermore, epigenetic or pharmacological enhancement of BDNF-trkB
      signaling could be a promising strategy for reversing cognitive aging.

PMID- 22159098
TI  - Sleep spindles in humans: insights from intracranial EEG and unit recordings.
AB  - Sleep spindles are an electroencephalographic (EEG) hallmark of non-rapid eye
      movement (NREM) sleep and are believed to mediate many sleep-related functions,
      from memory consolidation to cortical development. Spindles differ in location,
      frequency, and association with slow waves, but whether this heterogeneity may
      reflect different physiological processes and potentially serve different
      functional roles remains unclear. Here we used a unique opportunity to record
      intracranial depth EEG and single-unit activity in multiple brain regions of
      neurosurgical patients to better characterize spindle activity in human sleep. We
      find that spindles occur across multiple neocortical regions, and less frequently
      also in the parahippocampal gyrus and hippocampus. Most spindles are spatially
      restricted to specific brain regions. In addition, spindle frequency is
      topographically organized with a sharp transition around the supplementary motor
      area between fast (13-15 Hz) centroparietal spindles often occurring with slow
      wave up-states, and slow (9-12 Hz) frontal spindles occurring 200 ms later on
      average. Spindle variability across regions may reflect the underlying
      thalamocortical projections. We also find that during individual spindles,
      frequency decreases within and between regions. In addition, deeper NREM sleep is
      associated with a reduction in spindle occurrence and spindle frequency.
      Frequency changes between regions, during individual spindles, and across sleep
      may reflect the same phenomenon, the underlying level of thalamocortical
      hyperpolarization. Finally, during spindles neuronal firing rates are not
      consistently modulated, although some neurons exhibit phase-locked discharges.
      Overall, anatomical considerations can account well for regional spindle
      characteristics, while variable hyperpolarization levels can explain differences
      in spindle frequency.

PMID- 22159099
TI  - Early-life experience decreases drug-induced reinstatement of morphine CPP in
      adulthood via microglial-specific epigenetic programming of anti-inflammatory IL
      10 expression.
AB  - A critical component of drug addiction research involves identifying novel
      biological mechanisms and environmental predictors of risk or resilience to drug
      addiction and associated relapse. Increasing evidence suggests microglia and
      astrocytes can profoundly affect the physiological and addictive properties of
      drugs of abuse, including morphine. We report that glia within the rat nucleus
      accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine
      expression, which predicts future reinstatement of morphine conditioned place
      preference (CPP) following a priming dose of morphine. This glial response to
      morphine is influenced by early-life experience. A neonatal handling paradigm
      that increases the quantity and quality of maternal care significantly increases
      baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc,
      attenuates morphine-induced glial activation, and prevents the subsequent
      reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and
      reinstatement of CPP are negatively correlated, suggesting a protective role for
      this specific cytokine against morphine-induced glial reactivity and drug-induced
      reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10
      within the NAcc early in development, and this is maintained into adulthood via
      decreased methylation of the IL-10 gene specifically within microglia. The effect
      of neonatal handling is mimicked by pharmacological modulation of glia in
      adulthood with ibudilast, which increases IL-10 expression, inhibits morphine
      induced glial activation within the NAcc, and prevents reinstatement of morphine
      CPP. Taken together, we have identified a novel gene * early-life environment
      interaction on morphine-induced glial activation and a specific role for glial
      activation in drug-induced reinstatement of drug-seeking behavior.

PMID- 22159100
TI  - Impaired endogenously evoked automated reaching in Parkinson's disease.
AB  - Intended reaches triggered by exogenous targets often coexist with spontaneous,
      automated movements that are endogenously activated. It has been posited that
      Parkinson's disease (PD) primarily impairs automated movements, but it is unknown
      to what extent this may affect multijoint/limb control, particularly when
      patients are off their dopaminergic medications. Here we tested nine human
      patients with PD while off dopaminergic medication versus nine age-matched normal
      controls (NCs). Participants performed intentional reaches forward to a target in
      a dark room and then transitioned back to their initial posture. Upon target
      flash, three forms of guidance were used: (1) memory with eyes closed, (2)
      continuous target vision only, and (3) vision of their moving finger only. The
      trajectories of their arm joints were measured and their joint velocities
      decomposed into the (intended) task-relevant and the (spontaneous) task
      incidental degrees of freedom (DOF). We also measured the balance between these
      two subsets of DOF as these movements unfolded. In PD patients we found that the
      incidental DOF values were abnormally variable during the retracting movements
      and prevailed over the task-relevant DOF values. By contrast, their forward
      intentional motions were abnormally dominated by the task-relevant components.
      Moreover, the patients abruptly transitioned between voluntary and automated
      modes of joint control, and, unlike NCs, the type of visual guidance
      differentially affected their postural trajectories. These findings lend support
      to an emerging view that there is a loss of automated control in PD patients that
      contributes to impairments in voluntary control, and that basal ganglia-cortical
      circuits are critical for the maintenance and balance of multijoint control.

PMID- 22159103
TI  - Anticipatory saccade target processing and the presaccadic transfer of visual
      features.
AB  - As we shift our gaze to explore the visual world, information enters cortex in a
      sequence of successive snapshots, interrupted by phases of blur. Our experience,
      in contrast, appears like a movie of a continuous stream of objects embedded in a
      stable world. This perception of stability across eye movements has been linked
      to changes in spatial sensitivity of visual neurons anticipating the upcoming
      saccade, often referred to as shifting receptive fields (Duhamel et al., 1992;
      Walker et al., 1995; Umeno and Goldberg, 1997; Nakamura and Colby, 2002). How
      exactly these receptive field dynamics contribute to perceptual stability is
      currently not clear. Anticipatory receptive field shifts toward the future,
      postsaccadic position may bridge the transient perisaccadic epoch (Sommer and
      Wurtz, 2006; Wurtz, 2008; Melcher and Colby, 2008). Alternatively, a presaccadic
      shift of receptive fields toward the saccade target area (Tolias et al., 2001)
      may serve to focus visual resources onto the most relevant objects in the
      postsaccadic scene (Hamker et al., 2008). In this view, shifts of feature
      detectors serve to facilitate the processing of the peripheral visual content
      before it is foveated. While this conception is consistent with previous
      observations on receptive field dynamics and on perisaccadic compression (Ross et
      al., 1997; Morrone et al., 1997; Kaiser and Lappe, 2004), it predicts that
      receptive fields beyond the saccade target shift toward the saccade target rather
      than in the direction of the saccade. We have tested this prediction in human
      observers via the presaccadic transfer of the tilt-aftereffect (Melcher, 2007).

PMID- 22159101
TI  - Chronic perinatal hypoxia reduces glutamate-aspartate transporter function in
      astrocytes through the Janus kinase/signal transducer and activator of
      transcription pathway.
AB  - The cellular and molecular mechanisms that govern the response of the perinatal
      brain to injury remain largely unexplored. We investigated the role of white
      matter astrocytes in a rodent model of diffuse white matter injury produced by
      exposing neonatal mice to chronic hypoxia-a paradigm that mimics brain injury in
      premature infants. We demonstrate the absence of reactive gliosis in the immature
      white matter following chronic hypoxia, as determined by astrocyte proliferation
      index and glial fibrillary acidic protein levels. Instead, Nestin expression in
      astrocytes is transiently increased, and the glial-specific glutamate
      transporters glutamate-aspartate transporter (GLAST) and glutamate transporter 1
      (GLT-1) are reduced. Finally, we demonstrate that Janus kinase (JAK)/signal
      transducer and activator of transcription (STAT) signaling-which is important in
      both astrocyte development and response to injury-is reduced in the white matter
      following hypoxia, as well as in primary astrocytes exposed to hypoxia in vitro.
      Hypoxia and JAK/STAT inhibition reduce glutamate transporter expression in
      astrocytes, but unlike hypoxia JAK/STAT inhibition downregulates GLAST expression
      without affecting GLT-1, as demonstrated in vitro by treatment with JAK inhibitor
      I and in vivo by treatment with the JAK/STAT inhibitor AG490 [(E)-2-cyano-3-(3,4
      dihydrophenyl)-N-(phenylmethyl)-2-propenamide]. Our findings (1) demonstrate
      specific changes in astrocyte function after perinatal hypoxia, which might
      contribute to the particular pathogenesis of perinatal white matter injury, (2)
      provide evidence that at least part of these changes result from a disturbance of
      the JAK/STAT pathway by hypoxia, and (3) identify JAK/STAT signaling as a
      potential therapeutic target to restore normal GLAST expression and uptake of
      glutamate after perinatal brain injury.

PMID- 22159102
TI  - State-dependent function of neocortical chandelier cells.
AB  - Chandelier (axoaxonic) cells (ChCs) are a distinct group of GABAergic
      interneurons that innervate the axon initial segments of pyramidal cells.
      However, their circuit role and the function of their clearly defined anatomical
      specificity remain unclear. Recent work has demonstrated that chandelier cells
      can produce depolarizing GABAergic PSPs, occasionally driving postsynaptic
      targets to spike. On the other hand, other work suggests that ChCs are
      hyperpolarizing and may have an inhibitory role. These disparate functional
      effects may reflect heterogeneity among ChCs. Here, using brain slices from
      transgenic mouse strains, we first demonstrate that, across different neocortical
      areas and genetic backgrounds, upper Layer 2/3 ChCs belong to a single
      electrophysiologically and morphologically defined population, extensively
      sampling Layer 1 inputs with asymmetric dendrites. Consistent with being a single
      cell type, we find electrical coupling between ChCs. We then investigate the
      effect of chandelier cell activation on pyramidal neuron spiking in several
      conditions, ranging from the resting membrane potential to stimuli designed to
      approximate in vivo membrane potential dynamics. We find that under quiescent
      conditions, chandelier cells are capable of both promoting and inhibiting spike
      generation, depending on the postsynaptic membrane potential. However, during in
      vivo-like membrane potential fluctuations, the dominant postsynaptic effect was a
      strong inhibition. Thus, neocortical chandelier cells, even from within a
      homogeneous population, appear to play a dual role in the circuit, helping to
      activate quiescent pyramidal neurons, while at the same time inhibiting active
      ones.

PMID- 22159104
TI  - Neurons in dorsal visual area V5/MT signal relative disparity.
AB  - Judgments of visual depth rely crucially on the relative binocular disparity
      between two visual features. While areas of ventral visual cortex contain neurons
      that signal the relative disparity between spatially adjacent visual features,
      the same tests in dorsal visual areas yield little evidence for relative
      disparity selectivity. We investigated the sensitivity of neurons in dorsal
      visual area V5/MT of macaque monkeys to relative disparity, using two
      superimposed, transparent planes composed of dots moving in opposite directions.
      The separation of the planes in depth specifies their relative disparity, while
      absolute disparity can be altered independently by changing the binocular depth
      of the two planes with respect to the monkey's fixation point. Many V5/MT neurons
      were tuned to relative disparity, independent of the absolute disparities of the
      individual planes. For the two plane stimulus, neuronal responses were often
      linearly related to responses to the absolute disparity of each component plane
      presented individually, but some aspects of relative disparity tuning were not
      explained by linear combination. Selectivity for relative disparity could not
      predict whether neuronal firing was related to the monkeys' perceptual reports of
      the rotation direction of structure-from-motion figures centered on the plane of
      fixation. In sum, V5/MT neurons are not just selective for absolute disparity,
      but also code for relative disparity between visual features. This selectivity
      may be important for segmentation and depth order of moving visual features,
      particularly the processing of three-dimensional information in scenes viewed by
      an actively moving observer.

PMID- 22159105
TI  - Binocular disparity tuning and visual-vestibular congruency of multisensory
      neurons in macaque parietal cortex.
AB  - Many neurons in the dorsal medial superior temporal (MSTd) and ventral
      intraparietal (VIP) areas of the macaque brain are multisensory, responding to
      both optic flow and vestibular cues to self-motion. The heading tuning of visual
      and vestibular responses can be either congruent or opposite, but only congruent
      cells have been implicated in cue integration for heading perception. Because of
      the geometric properties of motion parallax, however, both congruent and opposite
      cells could be involved in coding self-motion when observers fixate a world-fixed
      target during translation, if congruent cells prefer near disparities and
      opposite cells prefer far disparities. We characterized the binocular disparity
      selectivity and heading tuning of MSTd and VIP cells using random-dot stimuli.
      Most (70%) MSTd neurons were disparity selective with monotonic tuning, and there
      was no consistent relationship between depth preference and congruency of visual
      and vestibular heading tuning. One-third of disparity-selective MSTd cells
      reversed their depth preference for opposite directions of motion [direction
      dependent disparity tuning (DDD)], but most of these cells were unisensory with
      no tuning for vestibular stimuli. Inconsistent with previous reports, the
      direction preferences of most DDD neurons do not reverse with disparity. By
      comparison to MSTd, VIP contains fewer disparity-selective neurons (41%) and very
      few DDD cells. On average, VIP neurons also preferred higher speeds and nearer
      disparities than MSTd cells. Our findings are inconsistent with the hypothesis
      that visual/vestibular congruency is linked to depth preference, and also suggest
      that DDD cells are not involved in multisensory integration for heading
      perception.

PMID- 22159106
TI  - Satiating effects of cocaine are controlled by dopamine actions in the nucleus
      accumbens core.
AB  - Intravenous cocaine intake in laboratory animals is characterized by periods of
      apparent drug satiety between regularly spaced earned injections. The reinforcing
      properties of cocaine are linked primarily to dopaminergic neurotransmission in
      the shell and not the core of nucleus accumbens. To determine whether the
      satiating effects of cocaine are similarly mediated, we perfused dopamine
      receptor agonists into the core or the shell during intravenous cocaine self
      administrations by rats. Neither D1-type (SKF38393) nor D2-type (quinpirole)
      agonist was effective when given alone. However, a combination of the two
      agonists perfused into the core but not the shell significantly increased the
      time between cocaine self-injections, decreasing the amount of earned intake.
      Together with previous findings, the current data suggest that the satiating and
      reinforcing effects of cocaine are mediated by different ventral striatal output
      neurons.

PMID- 22159107
TI  - Altered brain activation during visuomotor integration in chronic active cannabis
      users: relationship to cortisol levels.
AB  - Cannabis is the most abused illegal substance in the United States. Alterations
      in brain function and motor behavior have been reported in chronic cannabis
      users, but the results have been variable. The current study aimed to determine
      whether chronic active cannabis use in humans may alter psychomotor function,
      brain activation, and hypothalamic-pituitary-axis (HPA) function in men and
      women. Thirty cannabis users (16 men, 14 women, 18-45 years old) and 30 nondrug
      user controls (16 men, 14 women, 19-44 years old) were evaluated with
      neuropsychological tests designed to assess motor behavior and with fMRI using a
      3 Tesla scanner during a visually paced finger-sequencing task, cued by a
      flashing checkerboard (at 2 or 4 Hz). Salivary cortisol was measured to assess
      HPA function. Male, but not female, cannabis users had significantly slower
      performance on psychomotor speed tests. As a group, cannabis users had greater
      activation in BA 6 than controls, while controls had greater activation in the
      visual area BA 17 than cannabis users. Cannabis users also had higher salivary
      cortisol levels than controls (p = 0.002). Chronic active cannabis use is
      associated with slower and less efficient psychomotor function, especially in
      male users, as indicated by a shift from regions involved with automated visually
      guided responses to more executive or attentional control areas. The greater but
      altered brain activities may be mediated by the higher cortisol levels in the
      cannabis users, which in turn may lead to less efficient visual-motor function.

PMID- 22159108
TI  - Regional and temporal specificity of intrinsic plasticity mechanisms in rodent
      primary visual cortex.
AB  - Different neocortical regions are functionally specialized, but whether this
      specialization is reflected in the forms of plasticity present during
      developmental critical periods (CPs) is largely unknown. In rodent visual cortex,
      we recently showed that a form of intrinsic plasticity [LTP of intrinsic
      excitability (LTP-IE)] in the monocular region of the primary visual cortex (V1M)
      plays an important role in modulating cortical responsiveness following visual
      deprivation. Here we ask whether LTP-IE is present and similarly regulated by
      visual experience in the binocular region of the primary visual cortex (V1B),
      where inputs from the two eyes compete during the CP. In contrast to V1M, where
      LTP-IE is present throughout the CP, in V1B LTP-IE was only transiently expressed
      at the onset of the CP. Also distinct from V1M, brief monocular deprivation (MD)
      was unable to modulate LTP-IE magnitude in V1B, and even binocular deprivation
      (the equivalent of MD in V1M) could only influence LTP-IE expression during a
      narrow time window at the peak of the CP. Finally, we asked whether these
      differences depend on differences in sensory activation of the two areas during
      development. MD of ipsilateral inputs from before eye opening (to reduce
      competitive interactions) did not affect the pattern of LTP-IE expression in V1B.
      Further, the differences in plasticity in the two cortical areas persisted when
      animals were reared in the dark to remove all patterned visual input. Thus
      neocortical LTP-IE expression shows dramatic regional and temporal
      differentiation, and these differences are not driven by differences in sensory
      experience.

PMID- 22159109
TI  - Age-related changes in right middle frontal gyrus volume correlate with altered
      episodic retrieval activity.
AB  - Age-related deficits in episodic retrieval have been associated with volume
      reductions in the middle frontal gyrus (MFG). However, it remains unclear how
      this age-related reduction in MFG volume correlates with neural activity during
      retrieval. To address this, we conducted in vivo volumetry of the frontal cortex
      in young and older human adults and found more volume loss on the right than on
      the left MFG with age. We then examined how left and right MFG volume correlated
      with fMRI activity during successful retrieval of item, spatial context, and
      temporal context information in both age groups. In young adults, larger right
      MFG volume was positively correlated with greater activity in a commonly found
      episodic retrieval network that included bilateral dorsolateral prefrontal cortex
      (DLPFC) and bilateral inferior parietal cortex. Within this network, left DLPFC
      and right inferior parietal cortex activity predicted memory performance. In
      older adults, a positive structure-function association in DLPFC for either left
      or right MFG/DLPFC was not observed. Instead, right MFG volume was negatively
      correlated with activity in several regions in older adults, including the
      parahippocampal cortex (PHC) and anterior cingulate. Less activity in the PHC
      region predicted better item memory, and less activity in the anterior cingulate
      predicted better spatial context accuracy in older adults. We conclude that age
      related change in the structure-function association in MFG/DLPFC impacts
      retrieval activity and performance, and those older adults with larger right MFG
      volume attempt to compensate for this change by modifying activity in other brain
      regions to help retrieval performance.

PMID- 22159110
TI  - Cholinergic control in developing prefrontal-hippocampal networks.
AB  - The cholinergic drive enhances input processing in attentional and mnemonic
      context by interacting with the activity of prefrontal-hippocampal networks.
      During development, acetylcholine modulates neuronal proliferation,
      differentiation, and synaptic plasticity, yet its contribution to the maturation
      of cognitive processing resulting from early entrainment of neuronal networks in
      oscillatory rhythms remains widely unknown. Here we show that cholinergic
      projections growing into the rat prefrontal cortex (PFC) toward the end of the
      first postnatal week boost the generation of nested gamma oscillations
      superimposed on discontinuous spindle bursts by acting on functional muscarinic
      but not nicotinic receptors. Although electrical stimulation of cholinergic
      nuclei increased the occurrence of nested gamma spindle bursts by 41%,
      diminishment of the cholinergic input by either blockade of the receptors or
      chronic immunotoxic lesion had the opposite effect. This activation of locally
      generated gamma episodes by direct cholinergic projections to the PFC was
      accompanied by indirect modulation of underlying spindle bursts via cholinergic
      control of hippocampal theta activity. With ongoing maturation and switch of
      network activity from discontinuous bursts to continuous theta-gamma rhythms,
      accumulating cholinergic projections acting on both muscarinic and nicotinic
      receptors mediated the transition from high-amplitude slow to low-amplitude fast
      rhythms in the PFC. By exerting multiple actions on the oscillatory entrainment
      of developing prefrontal-hippocampal networks, the cholinergic input may refine
      them for later gating processing in executive and mnemonic tasks.

PMID- 22159111
TI  - Noise in brain activity engenders perception and influences discrimination
      sensitivity.
AB  - Behavioral and brain responses to identical stimuli can vary with experimental
      and task parameters, including the context of stimulus presentation or attention.
      More surprisingly, computational models suggest that noise-related random
      fluctuations in brain responses to stimuli would alone be sufficient to engender
      perceptual differences between physically identical stimuli. In two experiments
      combining psychophysics and EEG in healthy humans, we investigated brain
      mechanisms whereby identical stimuli are (erroneously) perceived as different
      (higher vs lower in pitch or longer vs shorter in duration) in the absence of any
      change in the experimental context. Even though, as expected, participants'
      percepts to identical stimuli varied randomly, a classification algorithm based
      on a mixture of Gaussians model (GMM) showed that there was sufficient
      information in single-trial EEG to reliably predict participants' judgments of
      the stimulus dimension. By contrasting electrical neuroimaging analyses of
      auditory evoked potentials (AEPs) to the identical stimuli as a function of
      participants' percepts, we identified the precise timing and neural correlates
      (strength vs topographic modulations) as well as intracranial sources of these
      erroneous perceptions. In both experiments, AEP differences first occurred ~100
      ms after stimulus onset and were the result of topographic modulations following
      from changes in the configuration of active brain networks. Source estimations
      localized the origin of variations in perceived pitch of identical stimuli within
      right temporal and left frontal areas and of variations in perceived duration
      within right temporoparietal areas. We discuss our results in terms of providing
      neurophysiologic evidence for the contribution of random fluctuations in brain
      activity to conscious perception.

PMID- 22159112
TI  - Iron and iron regulatory proteins in amoeboid microglial cells are linked to
      oligodendrocyte death in hypoxic neonatal rat periventricular white matter
      through production of proinflammatory cytokines and reactive oxygen/nitrogen
      species.
AB  - This study was aimed to examine the role of iron in causing periventricular white
      matter (PWM) damage following a hypoxic injury in the developing brain. Along
      with iron, the expression of iron regulatory proteins (IRPs) and transferrin
      receptor (TfR), which are involved in iron acquisition, was also examined in the
      PWM by subjecting 1-d-old Wistar rats to hypoxia. Apart from an increase in iron
      levels in PWM, Perls' iron staining showed an increase of intracellular iron in
      the preponderant amoeboid microglial cells (AMCs) in the tissue. In response to
      hypoxia, the protein levels of IRP1, IRP2, and TfR in PWM and AMCs were
      significantly increased. In primary microglial cultures, administration of iron
      chelator deferoxamine reduced the generation of iron-induced reactive oxygen and
      nitrogen species and proinflammatory cytokines such as tumor necrosis factor
      alpha and interleukin-1beta. Primary oligodendrocytes treated with conditioned
      medium from hypoxic microglia exhibited reduced glutathione levels, increased
      lipid peroxidation, upregulated caspase-3 expression, and reduced proliferation.
      This was reversed to control levels on treatment with conditioned medium from
      deferoxamine treated hypoxic microglia; also, there was reduction in apoptosis of
      oligodendrocytes. The present results suggest that excess iron derived primarily
      from AMCs might be a mediator of oligodendrocyte cell death in PWM following
      hypoxia in the neonatal brain.

PMID- 22159113
TI  - Felt and seen pain evoke the same local patterns of cortical activity in insular
      and cingulate cortex.
AB  - The discovery of regions in the human brain (e.g., insula and cingulate cortex)
      that activate both under direct exposure to pain and when perceiving pain in
      others has been interpreted as a neural signature of empathy. However, this
      overlap raises the question of whether it may reflect a unique distributed
      population of bimodal neurons or, alternatively, the activity of intermingled but
      independent populations. We used fMRI on 28 female volunteers and used
      multivariate pattern analysis techniques to probe for more fine-grain spatial
      representations of seen and felt pain. Using a whole-brain approach, we found
      that only in the anterior insula (bilaterally) the distribution of cortical
      activity evoked by seeing another person's hand in pain was spatially similar to
      that of pain felt on one's own hand. Subsequent region of interest analyses also
      implicated the middle insula (right hemisphere) and the middle cingulate cortex.
      Furthermore, for the anterior insula, the spatial distribution of activity
      associated with one's pain also replicates that of the perception of negative but
      painless stimuli. Our data show how the neural representations of aversive events
      affecting oneself are also recruited when the same events affect others, and
      provide the stronger evidence thus far of a unique distributed cortical ensemble
      coding for aversive events regardless of the subject who is affected.

PMID- 22159114
TI  - Haploinsufficiency of human APOE reduces amyloid deposition in a mouse model of
      amyloid-beta amyloidosis.
AB  - The epsilon4 allele of the apolipoprotein E (APOE) gene is the strongest genetic
      risk factor for Alzheimer's disease (AD). Evidence suggests that the effect of
      apoE isoforms on amyloid-beta (Abeta) accumulation in the brain plays a critical
      role in AD pathogenesis. Like in humans, apoE4 expression in animal models that
      develop Abeta amyloidosis results in greater Abeta and amyloid deposition than
      with apoE3 expression. However, whether decreasing levels of apoE3 or apoE4 would
      promote or attenuate Abeta-related pathology has not been directly addressed. To
      determine the effect of decreasing human apoE levels on Abeta accumulation in
      vivo, we generated human APOE isoform haploinsufficient mouse models by crossing
      APPPS1-21 mice with APOE isoform knock-in mice. By genetically manipulating APOE
      gene dosage, we demonstrate that decreasing human apoE levels, regardless of
      isoform status, results in significantly decreased amyloid plaque deposition and
      microglial activation. These differences in amyloid load between apoE3- and apoE4
      expressing mice were not due to apoE4 protein being present at lower levels than
      apoE3. These data suggest that current therapeutic strategies to increase apoE
      levels without altering its lipidation state may actually worsen Abeta
      amyloidosis, while increasing apoE degradation or inhibiting its synthesis may be
      a more effective treatment approach.

PMID- 22159116
TI  - Contextual knowledge configures attentional control networks.
AB  - Contextual cues are predictive and provide behaviorally relevant information;
      they are not the main objective of the current task but can make behavior more
      efficient. Using fMRI, we investigated the brain networks involved in
      representing contextual information and translating it into an attentional
      control signal. Human subjects performed a visual search task for a low-contrast
      target accompanied by a single non-target that was either perceptually similar or
      more salient (i.e., higher contrast). Shorter reaction times (RTs) and higher
      accuracy were found on salient trials, suggesting that the salient item was
      rapidly identified as a non-target and immediately acts as a spatial "anti-cue"
      to reorient attention to the target. The relative saliency of the non-target
      determined BOLD responses in the left temporoparietal junction (TPJ) and inferior
      frontal gyrus (IFG). IFG correlated with RT specifically on salient non-target
      trials. In contrast, bilateral dorsal frontoparietal regions [including the
      frontal eye fields (FEFs)] were correlated with RT in all conditions. Effective
      connectivity analyses using dynamic causal modeling found an excitatory pathway
      from TPJ to IFG to FEF, suggesting that this was the pathway by which the
      contextual cue was translated into an attentional control signal that facilitated
      behavior. Additionally, the connection from FEF to TPJ was negatively modulated
      during target-similar trials, consistent with the inhibition of TPJ by dorsal
      attentional control regions during top-down serial visual search. We conclude
      that left TPJ and IFG form a sensory-driven network that integrates contextual
      knowledge with ongoing sensory information to provide an attentional control
      signal to FEF.

PMID- 22159115
TI  - Prion protein promotes growth cone development through reggie/flotillin-dependent
      N-cadherin trafficking.
AB  - The role of prion protein (PrP) is insufficiently understood partially because
      PrP-deficient (-/-) neurons from C57BL/6J mice seem to differentiate normally and
      are functionally mildly impaired. Here, we reassessed this notion and,
      unexpectedly, discovered that PrP(-/-) hippocampal growth cones were abnormally
      small and poor in filopodia and cargo-containing vesicles. Based on our findings
      that PrP-PrP trans-interaction recruits E-cadherin to cell contact sites and
      reggie microdomains, and that reggies are essential for growth by regulating
      membrane trafficking, we reasoned that PrP and reggie might promote cargo (N
      cadherin) delivery via PrP-reggie-connected signaling upon PrP activation (by PrP
      Fc-induced trans-interaction). In wild-type but not PrP(-/-) neurons, PrP
      activation led to (1) enhanced PrP-reggie cocluster formation, (2) reggie
      associated fyn and MAP kinase activation, (3) Exo70 and N-cadherin (cargo)
      recruitment to reggie, (4) the preference of the growth cone for PrP-Fc as
      substrate, and (5) longer neurites. Conversely, PrP-reggie-induced N-cadherin
      recruitment was blocked by mutant TC10, the GTPase downstream of reggie,
      triggering exocyst-assisted cargo delivery. This implies that PrP functions in
      reggie-mediated signaling and cargo trafficking, thus promoting growth cone
      complexity and vitality and thereby growth cone elongation.

PMID- 22159117
TI  - Early improved and late defective cognition is reflected by dendritic spines in
      Tau.P301L mice.
AB  - Cognitive demise correlates with progressive brain tauopathy in dementing
      patients. Improved cognition of young Tau.P301L mice contrasts with dysfunction
      later in life and remains unexplained (Boekhoorn et al., 2006). To unravel early
      mechanisms, we composed a correlative time line of clinical symptoms, cognitive
      defects, and biochemical and pathological traits, including comprehensive
      analysis of dendritic spines in specified regions of the cortex and hippocampus
      of young and adult Tau.P301L mice. Remarkably, young Tau.P301L mice have not
      more, but more mature spines than wild-type mice, revealing the anatomical
      substrate for their improved cognition and LTP. Spine maturation remained high in
      the hippocampus of adult Tau.P301L mice. However, spines regressed in length
      paralleling impaired cognition and increased Tau phosphorylation (Terwel et al.,
      2005). Conversely, spine maturation was unaffected in adult Tau.4R mice, while
      spine density was increased and length reduced similar to Tau.P301L mice. To
      explain how protein Tau promoted spinogenesis, we analyzed hippocampal
      synaptosomes and dendritic spines for mouse and human Tau. While synaptosomes
      were positive for both mouse and human Tau, weak variable reaction in spines was
      observed only after fixation according to Bouin. Mouse Tau was absent from spines
      in wild-type mice, dissociating the pathological actions of Tau in transgenic
      mice by relocalization into dendrites and spines from the physiological actions
      of protein Tau in axons only. We conclude that mutant protein Tau modulates
      cognition and morphology of spines similarly and in both directions, with
      pathology later in life coinciding with increased phosphorylation and
      relocalization of Tau from axons to soma and processes.

PMID- 22159119
TI  - Reduced white matter integrity is related to cognitive instability.
AB  - Increased performance variability has been demonstrated in several groups and
      conditions, including aging and cognitive decline. Structural brain
      characteristics underlying this phenomenon have so far been elusive. However,
      there is reason to expect that disconnectivity in associative pathways, whether
      caused by immature or degraded white matter (WM) tracts, will increase
      performance variability by neural noise. The aim of this study was to test
      whether the quality of WM, measured by diffusion tensor imaging, is related to
      performance variability in healthy adults. Intraindividual standard deviation of
      the reaction time (sdRT) across trials and median reaction time (mRT) from 270
      participants were obtained from a speeded continuous performance task (Eriksen
      flanker task) with two conditions (congruent, incongruent). Tract-based spatial
      statistics was used to test the relationship with diffusion characteristics
      [fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD), axial
      diffusion (AD)]. Robust relationships between sdRT and all diffusion measures
      were found in most WM areas, independently of mRT, age, and sex. The effects were
      anatomically more widespread in the congruent than the incongruent condition,
      covering almost 50% of the voxels for RD and MD, and >25% of the voxels for FA
      and AD. Partial betas were in the range 0.45-0.55, and the strength of the
      relationships increased significantly with age. For mRT, the effects were smaller
      and unstable across condition. We concluded that performance variability is a
      likely consequence of individual differences in WM integrity, and that it is a
      promising behavioral correlate of individual differences in WM microstructure.

PMID- 22159118
TI  - Neuron-specific effects of interleukin-1beta are mediated by a novel isoform of
      the IL-1 receptor accessory protein.
AB  - In the CNS, interleukin-1beta (IL-1beta) is synthesized and released during
      injury, infection, and disease, mediating inflammatory responses. However, IL
      1beta is also present in the brain under physiological conditions, and can
      influence hippocampal neuronal function. Several cell-specific IL-1-mediated
      signaling pathways and functions have been identified in neurons and astrocytes,
      but their mechanisms have not been fully defined. In astrocytes, IL-1beta induced
      both the p38 MAPK and NF-kappaB (nuclear factor kappaB) pathways regulating
      inflammatory responses, however in hippocampal neurons IL-1beta activated p38 but
      not NF-kappaB. Additionally, IL-1beta induced Src phosphorylation at 0.01 ng/ml
      in hippocampal neurons, a dose 1000-fold lower than that used to stimulate
      inflammatory responses. IL-1 signaling requires the type 1 IL-1 receptor and the
      IL-1 receptor accessory protein (IL-1RAcP) as a receptor partner. We previously
      reported a novel isoform of the IL-1RAcP, IL-1RAcPb, found exclusively in CNS
      neurons. In this study, we demonstrate that AcPb specifically mediates IL-1beta
      activation of p-Src and potentiation of NMDA-induced calcium influx in mouse
      hippocampal neurons in a dose-dependent manner. Mice lacking the AcPb, but
      retaining the AcP, isoform were deficient in IL-1beta regulation of p-Src in
      neurons. AcPb also played a modulatory role in the activation of p38 MAPK, but
      had no effect on NF-kappaB signaling. The restricted expression of AcPb in CNS
      neurons, therefore, governs specific neuronal signaling and functional responses
      to IL-1beta.

PMID- 22159121
TI  - Involvement of NOX1/NADPH oxidase in morphine-induced analgesia and tolerance.
AB  - The involvement of reactive oxygen species (ROS) in morphine-induced analgesia
      and tolerance has been suggested, yet how and where ROS take part in these
      processes remains largely unknown. Here, we report a novel role for the
      superoxide-generating enzyme NOX1/NADPH oxidase in the regulation of analgesia
      and acute analgesic tolerance. In mice lacking Nox1 (Nox1(-/Y)), the magnitude of
      the analgesia induced by morphine was significantly augmented. More importantly,
      analgesic tolerance induced by repeated administration of morphine was
      significantly suppressed compared with that in the littermates, wild-type
      Nox1(+/Y). In a membrane fraction obtained from the dorsal spinal cord, no
      difference was observed in morphine-induced [(35)S]GTPgammaS-binding between the
      genotypes, whereas morphine-stimulated GTPase activity was significantly
      attenuated in Nox1(-/Y). At 2 h after morphine administration, a significant
      decline in [(35)S]GTPgammaS-binding was observed in Nox1(+/Y) but not in Nox1(
      /Y). No difference in the maximal binding and affinity of [(3)H]DAMGO was
      observed between the genotypes, but the translocation of protein kinase C
      isoforms to the membrane fraction following morphine administration was almost
      completely abolished in Nox1(-/Y). Finally, the phosphorylation of RGS9-2 and
      formation of a complex by Galphai2/RGS9-2 with 14-3-3 found in morphine-treated
      Nox1(+/Y) were significantly suppressed in Nox1(-/Y). Together, these results
      suggest that NOX1/NADPH oxidase attenuates the pharmacological effects of opioids
      by regulating GTPase activity and the phosphorylation of RGS9-2 by protein kinase
      C. NOX1/NADPH oxidase may thus be a novel target for the development of adjuvant
      therapy to retain the beneficial effects of morphine.

PMID- 22159120
TI  - Terminal field and firing selectivity of cholecystokinin-expressing interneurons
      in the hippocampal CA3 area.
AB  - Hippocampal oscillations reflect coordinated neuronal activity on many
      timescales. Distinct types of GABAergic interneuron participate in the
      coordination of pyramidal cells over different oscillatory cycle phases. In the
      CA3 area, which generates sharp waves and gamma oscillations, the contribution of
      identified GABAergic neurons remains to be defined. We have examined the firing
      of a family of cholecystokinin-expressing interneurons during network
      oscillations in urethane-anesthetized rats and compared them with firing of CA3
      pyramidal cells. The position of the terminals of individual visualized
      interneurons was highly diverse, selective, and often spatially coaligned with
      either the entorhinal or the associational inputs to area CA3. The spike timing
      in relation to theta and gamma oscillations and sharp waves was correlated with
      the innervated pyramidal cell domain. Basket and dendritic-layer-innervating
      interneurons receive entorhinal and associational inputs and preferentially fire
      on the ascending theta phase, when pyramidal cell assemblies emerge. Perforant
      path-associated cells, driven by recurrent collaterals of pyramidal cells fire on
      theta troughs, when established pyramidal cell assemblies are most active. In the
      CA3 area, slow and fast gamma oscillations occurred on opposite theta oscillation
      phases. Perforant-path-associated and some COUP-TFII-positive interneurons are
      strongly coupled to both fast and slow gamma oscillations, but basket and
      dendritic-layer-innervating cells are weakly coupled to fast gamma oscillations
      only. During sharp waves, different interneuron types are activated, inhibited,
      or remain unaffected. We suggest that specialization in pyramidal cell domain and
      glutamatergic input-specific operations, reflected in the position of GABAergic
      terminals, is the evolutionary drive underlying the diversity of cholecystokinin
      expressing interneurons.

PMID- 22159122
TI  - Insulin-like growth factor signaling regulates the timing of sensory cell
      differentiation in the mouse cochlea.
AB  - The mammalian auditory sensory epithelium, the organ of Corti, is a highly
      ordered cellular structure that comprises two types of auditory hair cells and
      several types of nonsensory supporting cells. During embryogenesis, a stereotyped
      sequence of cellular and molecular events is required for its development. These
      processes are assumed to be regulated by multiple growth and transcription
      factors. However, the majority of these factors have not been identified. One
      potential regulator of cochlear development is the insulin-like growth factor
      (IGF) signaling family. To examine the roles of the IGF pathway in inner ear
      formation, cochleae from Igf1r mutant mice were analyzed. Deletion of Igf1r leads
      to several changes in inner ear development including a shortened cochlear duct,
      a decrease in the total number of cochlear hair cells, and defects in the
      formation of the semicircular canals. In addition, maturation of the cochlear
      sensory epithelium was delayed at the transition point between cellular
      proliferation and differentiation. To determine the molecular basis for these
      defects, inhibition of IGF signaling was replicated pharmacologically in vitro.
      Results indicated that IGF signaling regulates cochlear length and hair cell
      number as well as Atoh1 expression through the phosphatidylinositol 3-kinase/Akt
      signaling pathway. These results demonstrate novel roles for IGF signaling in
      inner ear development including regulation of vestibular formation, length of the
      cochlear duct, and the number of cochlear hair cells. The results also provide
      new insights regarding the pathological processes that underlie auditory defects
      in the absence of IGF signaling in both humans and mice.

PMID- 22159123
TI  - First-pass selectivity for semantic categories in human anteroventral temporal
      lobe.
AB  - How the brain encodes the semantic concepts represented by words is a fundamental
      question in cognitive neuroscience. Hemodynamic neuroimaging studies have
      robustly shown that different areas of posteroventral temporal lobe are
      selectively activated by images of animals versus manmade objects. Selective
      responses in these areas to words representing animals versus objects are
      sometimes also seen, but they are task-dependent, suggesting that posteroventral
      temporal cortex may encode visual categories, while more anterior areas encode
      semantic categories. Here, using the spatiotemporal resolution provided by
      intracranial macroelectrode and microelectrode arrays, we report category
      selective responses to words representing animals and objects in human
      anteroventral temporal areas including inferotemporal, perirhinal, and entorhinal
      cortices. This selectivity generalizes across tasks and sensory modalities,
      suggesting that it represents abstract lexicosemantic categories. Significant
      category-specific responses are found in measures sensitive to synaptic activity
      (local field potentials, high gamma power, current sources and sinks) and unit
      firing (multiunit and single-unit activity). Category-selective responses can
      occur at short latency (as early as 130 ms) in middle cortical layers and thus
      are extracted in the first pass of activity through the anteroventral temporal
      lobe. This activation may provide input to posterior areas for iconic
      representations when required by the task, as well as to the hippocampal
      formation for categorical encoding and retrieval of memories, and to the amygdala
      for emotional associations. More generally, these results support models in which
      the anteroventral temporal lobe plays a primary role in the semantic
      representation of words.

PMID- 22159124
TI  - Different representations of potential and selected motor plans by distinct
      parietal areas.
AB  - Traditional theories have considered decision making as a separate neural process
      occurring before action planning. However, recent neurophysiological studies of
      spatial target selection have suggested that decision making and motor planning
      may be performed in an integrated manner. It was proposed that multiple potential
      plans are concurrently formed and the ultimately selected action simultaneously
      emerges within the same circuits (Shadlen and Newsome, 2001; Cisek and Kalaska,
      2010). In the present study, we recorded from the parietal reach region (PRR) and
      dorsal area 5 (area 5d) in the posterior parietal cortex (PPC) while monkeys
      performed a nonspatial effector (saccade vs reach) choice task. The results show
      that PRR encodes potential and selected reach plans whereas area 5d encodes only
      selected reach plans, suggesting a serial visuomotor cortical circuitry for
      nonspatial effector decisions. Thus, there appears to be a different flow of
      processing for decisions and planning for spatial target selection, which is more
      integrated, and nonspatial effector decisions between eye and limb movements,
      which are more serial.

PMID- 22159125
TI  - Downregulation of parvalbumin at cortical GABA synapses reduces network gamma
      oscillatory activity.
AB  - Postmortem and functional imaging studies of patients with psychiatric disorders,
      including schizophrenia, are consistent with a dysfunction of interneurons
      leading to compromised inhibitory control of network activity. Parvalbumin (PV)
      expressing, fast-spiking interneurons interacting with pyramidal neurons generate
      cortical gamma oscillations (30-80 Hz) that synchronize cortical activity during
      cognitive processing. In postmortem studies of schizophrenia patients, these
      interneurons show reduced PV and glutamic acid decarboxylase 67 (GAD67), an
      enzyme that synthesizes GABA, but the consequences of this downregulation are
      unclear. We developed a biophysically realistic and detailed computational model
      of a cortical circuit including asynchronous release from GABAergic interneurons
      to investigate how reductions in PV and GABA affect gamma oscillations induced by
      sensory stimuli. Networks with reduced GABA were disinhibited and had altered
      gamma oscillations in response to stimulation; PV-deficient GABA synapses had
      increased asynchronous release of GABA, which decreased the level of excitation
      and reduced gamma-band activity. Combined reductions of PV and GABA resulted in a
      diminished gamma-band oscillatory activity in response to stimuli, similar to
      that observed in schizophrenia patients. Our results suggest a mechanism by which
      reduced GAD67 and PV in fast-spiking interneurons may contribute to cortical
      dysfunction in schizophrenia and related psychiatric disorders.

PMID- 22159126
TI  - Synapsin I senses membrane curvature by an amphipathic lipid packing sensor
      motif.
AB  - Sustained neurotransmitter release at synapses during high-frequency synaptic
      activity involves the mobilization of synaptic vesicles (SVs) from the tightly
      clustered reserve pool (RP). Synapsin I (Syn I), a brain-specific peripheral
      membrane protein that undergoes activity-dependent cycles of SV association and
      dissociation, is implicated in RP organization via its ability to cluster SVs.
      Although Syn I has affinity for phospholipids, the mechanism for the reversible
      association of synapsin with SV membranes remains enigmatic. Here, we show that
      rat Syn I is able to sense membrane curvature via an evolutionary conserved
      amphipathic lipid packing sensor motif (ALPS). Deletion or mutational
      inactivation of the ALPS impairs the ability of Syn I to associate with highly
      curved membranes and with SVs. Furthermore, a Syn I mutant lacking ALPS displays
      defects in its ability to undergo activity-induced cycles of dispersion and
      reclustering in neurons and fails to induce vesicle clustering in vitro. Our data
      suggest a crucial role for ALPS-mediated sensing of membrane curvature in
      regulating synapsin function.

PMID- 22159127
TI  - Astrocyte calcium signaling transforms cholinergic modulation to cortical
      plasticity in vivo.
AB  - Global brain state dynamics regulate plasticity in local cortical circuits, but
      the underlying cellular and molecular mechanisms are unclear. Here, we
      demonstrate that astrocyte Ca(2+) signaling provides a critical bridge between
      cholinergic activation, associated with attention and vigilance states, and
      somatosensory plasticity in mouse barrel cortex in vivo. We investigated first
      whether a combined stimulation of mouse whiskers and the nucleus basalis of
      Meynert (NBM), the principal source of cholinergic innervation to the cortex,
      leads to enhanced whisker-evoked local field potential. This plasticity is
      dependent on muscarinic acetylcholine receptors (mAChR) and N-methyl-d-aspartic
      acid receptors (NMDARs). During the induction of this synaptic plasticity, we
      find that astrocytic [Ca(2+)](i) is pronouncedly elevated, which is blocked by
      mAChR antagonists. The elevation of astrocytic [Ca(2+)](i) is crucial in this
      type of synaptic plasticity, as the plasticity could not be induced in inositol
      1,4,5-trisphosphate receptor type 2 knock-out (IP(3)R2-KO) mice, in which
      astrocytic [Ca(2+)](i) surges are diminished. Moreover, NBM stimulation led to a
      significant increase in the extracellular concentration of the NMDAR coagonist d
      serine in wild-type mice when compared to IP(3)R2-KO mice. Finally, plasticity in
      IP(3)R2-KO mice could be rescued by externally supplying d-serine. Our data
      present coherent lines of in vivo evidence for astrocytic involvement in cortical
      plasticity. These findings suggest an unexpected role of astrocytes as a gate for
      cholinergic plasticity in the cortex.

PMID- 22159128
TI  - Regulation of hypothalamic signaling by tuberoinfundibular peptide of 39 residues
      is critical for the response to cold: a novel peptidergic mechanism of
      thermoregulation.
AB  - Euthermia is critical for mammalian homeostasis. Circuits within the preoptic
      hypothalamus regulate temperature, with fine control exerted via descending
      GABAergic inhibition of presympathetic motor neurons that control brown adipose
      tissue (BAT) thermogenesis and cutaneous vascular tone. The thermoregulatory role
      of hypothalamic excitatory neurons is less clear. Here we report peptidergic
      regulation of preoptic glutamatergic neurons that contributes to temperature
      regulation. Tuberoinfundibular peptide of 39 residues (TIP39) is a ligand for the
      parathyroid hormone 2 receptor (PTH2R). Both peptide and receptor are abundant in
      the preoptic hypothalamus. Based on PTH2R and vesicular glutamate transporter 2
      (VGlut2) immunolabeling in animals with retrograde tracer injection, PTH2R
      containing glutamatergic fibers are presynaptic to neurons projecting from the
      median preoptic nucleus (MnPO) to the dorsomedial hypothalamus. Transneuronal
      retrograde pathway tracing with pseudorabies virus revealed connectivity between
      MnPO VGlut2 and PTH2R neurons and BAT. MnPO injection of TIP39 increased body
      temperature by 2 degrees C for several hours. Mice lacking TIP39 signaling,
      either because of PTH2R-null mutation or brain delivery of a PTH2R antagonist had
      impaired heat production upon cold exposure, but no change in basal temperature
      and no impairment in response to a hot environment. Thus, TIP39 appears to act on
      PTH2Rs present on MnPO glutamatergic terminals to regulate their activation of
      projection neurons and subsequent sympathetic BAT activation. This excitatory
      mechanism of heat production appears to be activated on demand, during cold
      exposure, and parallels the tonic inhibitory GABAergic control of body
      temperature.

PMID- 22159129
TI  - Hippocampal function in healthy carriers of the CLU Alzheimer's disease risk
      variant.
AB  - Alzheimer's disease is a devastating, common, progressive dementia with
      considerable heritability. Recently, a genetic variant associated with the
      disease was discovered at CLU (rs11136000) with genome-wide support. Here we
      show, using an imaging genetics approach in a large genotyped sample, that
      healthy carriers of the variant exhibit altered coupling between hippocampus and
      prefrontal cortex during memory processing, mirroring clinical evidence of
      disturbed connectivity in patients and providing a neurogenetic mechanism for CLU
      associated risk and protection.

PMID- 22159133
TI  - Glutamate receptors and schizophrenia.

PMID- 22159130
TI  - Rapid disruption of axon-glial integrity in response to mild cerebral
      hypoperfusion.
AB  - Myelinated axons have a distinct protein architecture essential for action
      potential propagation, neuronal communication, and maintaining cognitive
      function. Damage to myelinated axons, associated with cerebral hypoperfusion,
      contributes to age-related cognitive decline. We sought to determine early
      alterations in the protein architecture of myelinated axons and potential
      mechanisms after hypoperfusion. Using a mouse model of hypoperfusion, we assessed
      changes in proteins critical to the maintenance of paranodes, nodes of Ranvier,
      axon-glial integrity, axons, and myelin by confocal laser scanning microscopy. As
      early as 3 d after hypoperfusion, the paranodal septate-like junctions were
      damaged. This was marked by a progressive reduction of paranodal Neurofascin
      signal and a loss of septate-like junctions. Concurrent with paranodal
      disruption, there was a significant increase in nodal length, identified by
      Nav1.6 staining, with hypoperfusion. Disruption of axon-glial integrity was also
      determined after hypoperfusion by changes in the spatial distribution of myelin
      associated glycoprotein staining. These nodal/paranodal changes were more
      pronounced after 1 month of hypoperfusion. In contrast, the nodal anchoring
      proteins AnkyrinG and Neurofascin 186 were unchanged and there were no overt
      changes in axonal and myelin integrity with hypoperfusion. A microarray analysis
      of white matter samples indicated that there were significant alterations in 129
      genes. Subsequent analysis indicated alterations in biological pathways,
      including inflammatory responses, cytokine-cytokine receptor interactions, blood
      vessel development, and cell proliferation processes. Our results demonstrate
      that hypoperfusion leads to a rapid disruption of key proteins critical to the
      stability of the axon-glial connection that is mediated by a diversity of
      molecular events.

PMID- 22159134
TI  - Subtypes of 5-HT receptors.

PMID- 22159132
TI  - Human Protein Reference Database and Human Proteinpedia as resources for
      phosphoproteome analysis.
AB  - Human Protein Reference Database (HPRD) is a rich resource of experimentally
      proven features of human proteins. Protein information in HPRD includes protein
      protein interactions, post-translational modifications, enzyme/substrate
      relationships, disease associations, tissue expression, and subcellular
      localization of human proteins. Although, protein-protein interaction data from
      HPRD has been widely used by the scientific community, its phosphoproteome data
      has not been exploited to its full potential. HPRD is one of the largest
      documentations of human phosphoproteins in the public domain. Currently,
      phosphorylation data in HPRD comprises of 95,016 phosphosites mapped on to 13,041
      proteins. Additionally, enzyme-substrate reactions responsible for 5930
      phosphorylation events were also documented. Significant improvements in
      technologies and high-throughput platforms in biomedical investigations led to an
      exponential increase of biological data and phosphoproteomic data in recent
      years. Human Proteinpedia, a community annotation portal developed by us, has
      also contributed to the significant increase in phosphoproteomic data in HPRD. A
      large number of phosphorylation events have been mapped on to reference sequences
      available in HPRD and Human Proteinpedia along with associated protein features.
      This will provide a platform for systems biology approaches to determine the role
      of protein phosphorylation in protein function, cell signaling, biological
      processes and their implication in human diseases. This review aims to provide a
      composite view of phosphoproteomic data pertaining to human proteins in HPRD and
      Human Proteinpedia.

PMID- 22159135
TI  - The emerging pharmacology of ethanol.
AB  - Historically, alcohol (ethanol) has been viewed as a non-specific CNS depressant,
      presumed to act equally on all bioelectric membranes. In contrast to this view,
      cellular electrophysiological studies, supported by anatomic and neurochemical
      evidence, support the emergence of a more specific pharmacological profile. Four
      regions of the rodent brain (cerebellum, hippocampus, locus coeruleus and
      inferior olive) have so far been examined. The effects of acute parenteral
      ethanol on specific identifiable neurons within these four regions are highly
      consistent, dose-related, and spontaneously reversible. Nevertheless, different
      patterns of effects are seen in each responsive region, ranging from general
      increased firing in inferior olive to generally depressed synaptic transmission
      in hippocampus, and with more subtle effects within the cerebellum and within the
      locus ceruleus. This survey of consistent but differing patterns of
      responsiveness to ethanol at specific time points after acute exposure, suggests
      that the global effects of ethanol on movement, on arousal and on emotions and
      memory must be composed of several distinct effects both within and across many
      cellular systems.

PMID- 22159136
TI  - Effects of the chronic administration of pyrithioxin on behaviour and cholinergic
      function in young and aged rats.
AB  - Behavioural effects were assessed in both young and old rats of the pyridine
      derivative pyrithioxin, which has been reported to elevate acetylcholine levels
      in several brain regions in old rats. Pyrithioxin was administered in rats' food
      according to two separate dosing regimens (200 and 600 mg kg( -1)) over a 6 week
      period. Spontaneous locomotor activity was measured weekly in photocell cages.
      Two measures of memory were used: one trial step-down passive avoidance, and
      spatial learning and retention in the Morris water maze. Pyrithioxin had no
      effect on locomotor activity or swim speed, but enhanced one trial passive
      avoidance retention in both young and old animals. The drug also enhanced
      sensitivity to foot shock and retention of the water maze in old animals.

PMID- 22159137
TI  - Changes in human whole blood 5-hydroxytryptamine (5-HT) and platelet 5-HT uptake
      during treatment with paroxetine, a selective 5-HT uptake inhibitor.
AB  - The effects of the specific 5-hydroxytryptamine (5-HT) reuptake inhibitor parox
      etine on whole blood 5-HT and the uptake of (3)H-5-HT by platelets was determined
      in 17 patients with resistant depression. The biochemical parameters were
      measured before paroxetine treatment, during treatment and after withdrawal of
      treatment. Two of the 17 subjects failed to complete the trial; of the remaining
      subjects 12 showed a marked decrease in whole blood 5-HT and (3)H-5-HT uptake
      into platelets. The remaining three patients showed a variable response both in
      terms of whole blood 5-HT and platelet uptake during paroxetine treatment. At the
      end of treatment blood 5-HT tended to return towards normal although this was
      delayed. There was no significant correlation between the change in blood 5-HT
      and Hamilton score during paroxetine treatment. The results confirm that
      inhibition of 5-HT uptake mech anisms are associated with decreased whole blood 5
      HT but that changes in whole blood 5- HT do not necessarily reflect the clinical
      efficacy of 5-HT uptake blocking drugs in the treatment of depression.

PMID- 22159138
TI  - Clinical efficacy of paroxetine in resistant depression.
AB  - The antidepressant effects of a specific reuptake inhibitor of 5
      hydroxytryptamine (5-HT), paroxetine, were tested in 24 patients with resistant
      depression who had failed to respond to conventional antidepressants after at
      least 4 weeks of treatment. A novel exper imental design was chosen in which all
      patients had 12 weeks of treatment beginning and ending with placebo therapy with
      6 weeks of active drug treatment at some point in between. Ratings of depressive
      symptoms were made using the Hamilton rating scale (HRS) for depression, and the
      checklist for unwanted effects and their severity was also recorded before and
      during treatment at 2 week intervals. The change from placebo to active
      paroxetine therapy was made using a double-blind procedure. Patients who made a
      significant placebo response in the first 2 weeks of treatment were excluded from
      further analysis; 20 patients completed the study and satisfied all criteria for
      inclusion. Both groups of showed a significant improvement in symptoms after 4
      weeks of paroxetine therapy. There were no significant treatment differences
      between the groups, but improvement in symptoms occurred sig nificantly later in
      the patients who had a longer period of initial placebo therapy. The experimental
      design also allowed study of withdrawal effects after stopping active treatment.
      There was no increase in adverse effects, including a subgroup associated with
      withdrawal problems, either during treatment with paroxetine or after the drug
      was stopped. The results suggest that paroxetine is probably an effective
      antidepressant, is well tolerated and has few adverse effects.

PMID- 22159139
TI  - The effect of 5,7-DHT-induced lesions of the median raphe nucleus and chronic
      desipramine administration upon motor behaviour of rats given intrahippocampal
      clonidine injection.
AB  - The role of serotonergic (5-HT) innervation of rat hippocampus in clonidine-
      induced behavioural effects was studied in naive and desipramine-pretreated
      animals. 5,7- DHT-lesions of the median raphe nucleus (MR) produced about 50 per
      cent decrease of serotonin and 5-hydroxyindoloacetic acid (5-HIAA) content in the
      rat cortex and hippocampus. Lesions of the MR also accelerated the attenuating
      effect of desipramine upon locomotor inhibition produced by intrahippocampal
      clonidine injections. In the forced swim test (FST) the MR lesion revealed the
      stimulatory potency of clonidine upon rat active behaviour, which was
      statistically significant. However, no further potentiation by MR lesions of DMI
      effects upon behavioural action of clonidine could be observed in this test. It
      is concluded that hippocampal serotonergic innervation plays a minor role in the
      antidepressant-induced changes in behavioural effects of clonidine, which
      probably occur via modulation of local alpha-adrenoceptors. It is also
      conceivable that the stimulatory effect of intrahippocampal clonidine injections
      in the forced swim test in MR-lesioned rats, may be due to the increase in the
      alpha-(1)-adrenoceptor function in this brain area.

PMID- 22159140
TI  - Interaction of nicotine with dopaminergic mechanisms assessed through drug
      discrimination and rotational behaviour in rats.
AB  - Biochemical and electrophysiological studies have suggested that nicotine may
      interact with dopaminergic systems so as to enhance the release and utilization
      of dopamine. The functional significance of these effects has been assessed using
      drug discrimination and rotational behaviour in rats. The dopamine antagonists
      haloperidol and Sch 23390 attenuated the discriminative stimulus effect of
      nicotine and reduced overall rates of responding. In contrast, droperidol and
      pimozide were without significant effect on discrimination of nicotine at doses
      that reduced response rates. There was partial generalization from nicotine to
      the dopamine D-1 agonist SKF 38393. In rats with unilateral, 6-hydroxydopamine
      lesions of the nigrostriatal dopamine pathway, nicotine produced rotation towards
      the side of the lesion, a characteristic effect of indirectly acting dopamine
      agonists such as amphetamine. The nico tinic-cholinergic antagonist mecamylamine,
      and haloperidol, blocked rotation produced by nicotine. A dose of nicotine that
      was too small to produce amphetamine-like effects itself enhanced both the
      discriminative stimulus and the rotational behaviour produced by amphetamine.
      However, mecamylamine did not weaken the discriminative effect of amphetamine.
      The results suggest that there may be a minor component of the nicotine
      discriminative stimulus that is mediated, indirectly, through a dopaminergic
      mechanism. There also appears to be a facilitatory, nicotinic influence on
      behavioural functions linked to the dopamine system.

PMID- 22159141
TI  - In memoriam: ole j. Rafaelsen, 13 april, 1930 to 20 august, 1987.

PMID- 22159142
TI  - Butylphenyl-functionalized Pt nanoparticles as CO-resistant electrocatalysts for
      formic acid oxidation.
AB  - Butylphenyl-functionalized Pt nanoparticles (Pt-BP) with an average core diameter
      of 2.93 +/- 0.49 nm were synthesized by the co-reduction of butylphenyl diazonium
      salt and H(2)PtCl(4). Cyclic voltammetric studies of the Pt-BP nanoparticles
      showed a much less pronounced hysteresis between the oxidation currents of formic
      acid in the forward and reverse scans, as compared to that on naked Pt surfaces.
      Electrochemical in situ FTIR studies confirmed that no adsorbed CO, a poisoning
      intermediate, was generated on the Pt-BP nanoparticle surface. These results
      suggest that functionalization of the Pt nanoparticles by butylphenyl fragments
      effectively blocked the CO poisoning pathway, most probably through third-body
      effects, and hence led to an apparent improvement of the electrocatalytic
      activity in formic acid oxidation.

PMID- 22159143
TI  - Prolactin down-regulates CD4+CD25hiCD127low/- regulatory T cell function in
      humans.
AB  - Among its many functions, prolactin (PRL) participates in immune responses and
      promotes the activation, differentiation and proliferation of T cells. However,
      the mechanisms by which PRL regulates regulatory T (T(reg)) cells are still
      unknown. Our goal was to determine whether PRL plays a role in T(reg) function.
      We measured the expression of PRL and its receptor in T(reg) and effector T
      (T(eff)) cells from 15 healthy individuals. We also evaluated the functional
      activity of T(reg) cells by examining proliferation and cytokine secretion in
      cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report
      that T(reg) cells constitutively expressed PRL receptor, whereas T(eff) cells
      required stimulation with anti-CD3/CD28 to induce PRL receptor expression.
      Expression of PRL was constitutive in both populations. We found that the
      addition of PRL inhibited the suppressor effect (proliferation) mediated by
      T(reg) cells in vitro, reducing suppression from 37.4 to 13% when PRL was added
      to co-cultures of T(reg) and T(eff) cells (P<0.05). Cultures treated with PRL
      favoured a Th1 cytokine profile, with increased production of TNF and IFNgamma.
      We report for the first time that PRL receptor expression was constitutive in
      T(reg) cells but not in T(eff) cells, which require stimulation to induce PRL
      receptor expression. PRL inhibited the suppressive function of T(reg) cells,
      apparently through the induced secretion of Th1 cytokines.

PMID- 22159144
TI  - Histidine-rich branched peptides as Cu(II) and Zn(II) chelators with potential
      therapeutic application in Alzheimer's disease.
AB  - Two histidine-rich branched peptides with one lysine as a branching unit have
      been designed and synthesized by solid-phase peptide synthesis. Their complex
      formation with Cu(II) and Zn(II) as well as their ability to attenuate the metal
      ion induced amyloid aggregation has been characterized. Both peptides can keep
      Cu(II) and Zn(II) in complexed forms at pH 7.4 and can bind two equivalents of
      metal ions in solutions with excess metal. The stoichiometry, stability and
      structure of the complexes formed have been determined by pH potentiometry, UV
      Vis spectrophotometry, circular dichroism, EPR and NMR spectroscopy and ESI-MS.
      Both mono- and bimetallic species have been detected over the whole pH range
      studied. The basic binding mode is either a tridentate {N(amino), N(amide),
      N(im)} or a histamine-type of coordination which is complemented by the binding
      of far imidazole or amino groups leading to macrochelate formation. The peptides
      were able to prevent Cu(II)-induced Abeta(1-40) aggregation but could not
      effectively compete for Zn(II) in vitro. Our results suggest that branched
      peptides containing potential metal-binding sites may be suitable metal chelators
      for reducing the risk of amyloid plaque formation in Alzheimer's disease.

PMID- 22159145
TI  - Voltage-dependent capacitance of metallic nanoparticles at a liquid/liquid
      interface.
AB  - A theoretical model is described for the voltage-dependent capacitance across the
      interface between two immiscible electrolytic solutions that is partially or
      completely covered with nanoparticles. The model is based on the description of
      competitive contributions of electrical double layers at the free interface and
      around nanoparticles. The effect of different system parameters is rationalised,
      and theoretical predictions are shown to be in agreement with available
      experimental data. The model provides a route for the characterisation of
      nanoparticle layers at liquid/liquid interfaces using capacitance measurements.

PMID- 22159146
TI  - Immediate pigment darkening: its evolutionary roles may include protection
      against folate photosensitization.
AB  - The evolution of dark human skin colors in tropical areas is possibly related to
      photoprotection of folates. However, natural folates absorb mainly UVB radiation,
      and too little UVB can penetrate down to folates in dermal vessels to cause
      serious damage. However, endogenous photosensitizers, like riboflavin and
      uroporphyrin, absorbing UVA and visible light, can cause photosensitization of
      folates. Immediate pigment darkening (IPD), generated by UVA, has an absorption
      spectrum covering those of the endogenous photosensitizers. IPD is most prominent
      for darker skin types, which were typical for populations living under tropical
      solar fluences. We here propose that the biological role of IPD is protection of
      folates against photodegradation, which would be of large evolutionary importance
      for early hominids.

PMID- 22159147
TI  - Mucin 16 is a functional selectin ligand on pancreatic cancer cells.
AB  - Selectins promote metastasis by mediating specific interactions between selectin
      ligands on tumor cells and selectin-expressing host cells in the
      microvasculature. Using affinity chromatography in conjunction with tandem mass
      spectrometry and bioinformatics tools, we identified mucin 16 (MUC16) as a novel
      selectin ligand expressed by metastatic pancreatic cancer cells. While up
      regulated in many pancreatic cancers, the biological function of sialofucosylated
      MUC16 has yet to be fully elucidated. To address this, we employed blot rolling
      and cell-free flow-based adhesion assays using MUC16 immunopurified from
      pancreatic cancer cells and found that it efficiently binds E- and L- but not P
      selectin. The selectin-binding determinants are sialofucosylated structures
      displayed on O- and N-linked glycans. Silencing MUC16 expression by RNAi markedly
      reduces pancreatic cancer cell binding to E- and L-selectin under flow. These
      findings provide a novel integrated perspective on the enhanced metastatic
      potential associated with MUC16 overexpression and the role of selectins in
      metastasis.

PMID- 22159148
TI  - Both acute and prolonged administration of EPO reduce cerebral and systemic
      vascular conductance in humans.
AB  - Administration of erythropoietin (EPO) has been linked to cerebrovascular events.
      EPO reduces vascular conductance, possibly because of the increase in hematocrit.
      Whether EPO in itself affects the vasculature remains unknown; here it was
      evaluated in healthy males by determining systemic and cerebrovascular variables
      following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk;
      n=8) administration of EPO, while the responsiveness of the vasculature was
      challenged during cycling exercise, with and without hypoxia. Prolonged
      administration of EPO increased hematocrit from 42.5 +/- 3.7 to 47.6 +/- 4.1%
      (P<0.01), whereas hematocrit was unaffected following acute EPO administration.
      Yet, the two EPO regimes increased arterial pressure similarly (by 8+/-4 and 7+/
      3 mmHg, respectively; P=0.01) through reduced vascular conductance (by 7+/-3 and
      5+/-2%; P<0.05). Also, both EPO regimes widened the arterial-to-jugular O(2)
      differences at rest as well as during normoxic and hypoxic exercise (P<0.01),
      which indicated reduced cerebral blood flow despite preserved dynamic cerebral
      autoregulation, and an increase in middle cerebral artery mean blood flow
      velocity (P<0.05), therefore, reflected vasoconstriction. Thus, administration of
      EPO to healthy humans lowers systemic and cerebral conductance independent of its
      effect on hematocrit.

PMID- 22159151
TI  - N-(5,6,7-trihydroquinolin-8-ylidene)-2-benzhydrylbenzenaminonickel halide
      complexes: synthesis, characterization and catalytic behavior towards ethylene
      polymerization.
AB  - A series of N-(5,6,7-trihydroquinolinylidene)-2-benzhydrylbenzenamine ligands was
      synthesized and characterized by (1)H/(13)C NMR and IR spectroscopy, and by
      elemental analysis. These ligands reacted with NiCl(2) or NiBr(2)(DME) to form
      the title halide complexes, which were also characterized by IR spectroscopy and
      elemental analysis. Single crystal X-ray diffraction revealed that the
      representative nickel complexes crystallized as centro-symmetric dimers with
      chloro-bridges linking distorted octahedral nickel centers. On activation with
      either methylaluminoxane (MAO) or diethylaluminium chloride (Et(2)AlCl), all
      nickel pre-catalysts showed high activities for ethylene polymerization,
      producing polyethylene with narrow molecular weight distribution, consistent with
      single-site catalysis. The nature of the ligands and reaction parameters were
      investigated and discussed in terms of their influence on the catalytic behavior
      of these nickel pre-catalysts.

PMID- 22159149
TI  - Nutritional and hormonal regulation of the TOR effector 4E-binding protein (4E
      BP) in the mosquito Aedes aegypti.
AB  - Mosquitoes require blood for egg development, and, as a consequence, they
      transmit pathogens of devastating diseases. Target of rapamycin (TOR) signaling
      is a key pathway linking blood feeding and egg development in the mosquito Aedes
      aegypti. We show that the regulation of the TOR effector translational repressor
      4E-BP is finely tuned to the nutritional requirements of the female mosquito, and
      it occurs at transcriptional and post-translational levels. Immediately after
      blood feeding, 4E-BP became hyperphosphorylated, suggesting rapid inhibition of
      its translational repression function. 4E-BP was highly phosphorylated after in
      vitro incubation of the fat body in the presence of amino acids; this
      phosphorylation was rapamycin insensitive, in contrast to another TOR target,
      S6K, phosphorylation of which was rapamycin sensitive. A high level of 4E-BP
      phosphorylation was also elicited by insulin. Rapamycin and the PI3K inhibitor
      LY294002 blocked insulin-mediated 4E-BP phosphorylation. RNA-interference
      depletion of the insulin receptor or Akt resulted in severe reduction of 4E-BP
      phosphorylation. Phosphorylation and stability of 4E-BP was dependent on its
      partner eIF4E translation initiation factor. Silencing of 4E-BP resulted in
      reduction of the life span of adult female mosquitoes. This study demonstrates a
      dual nutritional and hormonal control of 4E-BP and its role in mosquito egg
      development.

PMID- 22159152
TI  - Enhanced visible-light-driven photocatalysis of surface nitrided electrospun TiO2
      nanofibers.
AB  - Enhanced visible-light-driven photocatalysis of TiO(2) nanofibers have been
      prepared by the electrospinning method combined with a surface nitridation
      process. The visible-light-driven photo-catalytic activity of surface nitrided
      TiO(2) (N-TiO(2)) nanofibers has been evaluated using rhodamine B indicator, and
      it was found that the visible-light-driven photocatalytic activity of the
      electrospun TiO(2) nanofibers could be enhanced by nitridation in NH(3)
      atmosphere. The optimal visible-light photocatalytic activity of N-TiO(2)
      nanofibers exceeded that of pure TiO(2) nanofibers by a factor of more than 12.
      The nitridation temperature under NH(3) flow was found to play an important part
      in the performance of N-TiO(2) nanofibers, and the optimum temperature is 500 
      degrees C. Structure, morphology and photoluminescence of these nanofibers were
      studied by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS),
      transmission electron microscopy (TEM), scanning electron microscope (SEM) and
      photoluminescence (PL) spectroscopy. The mechanism of the enhancement of visible
      light-driven photocatalytic activity by surface nitridation has been discussed.

PMID- 22159153
TI  - A systematic analysis of heart transcriptome highlights divergent cardiovascular
      disease pathways between animal models and humans.
AB  - Animal models have been extensively used in the study of cardiovascular disease
      (CVD) and have provided important insights into disease pathogenesis and drug
      development. However, the level of conservation of gene expression patterns of
      the orthologous genes between human and animal models was unclear. To address
      this issue, we compared the expression of orthologous genes in human and four
      models (rhesus, rat, mouse and dog), based on 42 normal heart samples with high
      quality gene expression data. The results show that the global expression
      profiles between animal model and human orthologous genes are highly preserved.
      The phylogenetic tree inferred from the gene expression profiles has similar
      topology to that of the species tree. However, differentially expressed genes
      (DEGs) between human and each model were identified and these four gene datasets
      are enriched with different molecular functions, including hormone-receptor
      binding and geranyl transferase activity. The 65 overlapped DEGs between four
      sets are involved in thyroid cancer, proteasome systems, aminoacyl-tRNA
      biosynthesis and GST (Glycine, Serine and Threonine) metabolism, of which
      functions are divergent between models and humans. In addition, 46.2% (30/65) of
      the communal genes have been experimentally proven to be associated with
      cardiovascular disease. Next, we constructed a co-expression network based on
      intra- and inter-species variation, to elucidate the altered network
      organization. It indicates that these DEGs evolved as modules rather than
      independently. The integrated heart transcriptome data should provide a valuable
      resource for the in-depth understanding of cardiology and the development of
      cardiovascular disease models.

PMID- 22159154
TI  - Operando DRIFTS study of the redox and catalytic properties of CuO/Ce(1
      x)Tb(x)O(2-delta) (x = 0-0.5) catalysts: evidence of an induction step during CO
      oxidation.
AB  - Catalysts of 1 wt% copper oxide supported on cerium oxide or cerium-terbium mixed
      oxides are comparatively examined with respect to their redox and catalytic
      properties for CO oxidation. Characterization of the catalysts had shown that
      they contain highly dispersed CuO-type entities on the corresponding
      nanostructured fluorite supports with copper dispersion increasing with
      increasing amounts of terbium in the support. In contrast, the CO oxidation
      catalytic activity decreases with increasing amounts of terbium in the support.
      On the basis of operando-DRIFTS experiments, one of the factors that could
      explain such behaviour is related to the greater difficulty in generating reduced
      copper sites active for the reaction in the presence of terbium, which in turn is
      evidenced to constitute an induction stage. Analysis of the redox properties is
      complemented by XPS which confirms the greater resistance to copper reduction in
      the presence of terbium.

PMID- 22159155
TI  - State-resolved velocity map imaging of surface-scattered molecular flux.
AB  - This work describes a novel surface-scattering technique which combines resonance
      enhanced multiphoton ionization (REMPI) with velocity-map imaging (VMI) to yield
      quantum-state and 2D velocity component resolved distributions in the scattered
      molecular flux. As an initial test system, we explore hyperthermal scattering
      (E(inc) = 21(5) kcal mol(-1)) of jet cooled HCl from Au(111) on atomically flat
      mica surfaces at 500 K. The resulting images reveal 2D (v(in-plane) and v(out-of
      plane)) velocity distributions dominated by two primary features:
      trapping/thermal-desorption (TD) and a hyperthermal, impulsively scattering (IS)
      distribution. In particular, the IS component is strongly forward scattered and
      largely resolved in the velocity map images, which allows us to probe
      correlations between rotational and translational degrees of freedom in the IS
      flux without any model dependent deconvolution from the TD fraction. These
      correlations reveal that HCl molecules which have undergone a large decrease in
      velocity parallel to scattering plane have actually gained the most rotational
      energy, reminiscent of a dynamical energy constraint between these two degrees of
      freedom. The data are reduced to a rotational energy map that correlates <E(rot)>
      with velocity along and normal to the scattering plane, revealing that exchange
      occurs primarily between rotation and the in-plane kinetic energy component, with
      v(out-of-plane) playing a relatively minor role.

PMID- 22159156
TI  - Theoretical investigation on DNA/RNA base pairs mediated by copper, silver, and
      gold cations.
AB  - B3LYP density functional based computations were performed in order to
      characterize the interactions present in some Cu(+), Ag(+), and Au(+) metal ion
      mediated DNA and RNA base pairs from both structural and electronic points of
      view. Examined systems involve as ligands canonical Watson-Crick, Hoogsteen and
      Wobble base pairs. Two artificial Hoogsteen base pairs were also taken into
      account. Binding energy values indicate that complexes involving silver cations
      are less stable than those in which copper or gold are present, and propose a
      similar behaviour for these two latter ions. The nature of the bond linking metal
      ions and bases was described by the NBO analysis that suggests metal coordinative
      interactions to be covalent. An evaluation of the dispersion contributions for
      the investigated systems was performed with the B3LYP-D3 functional.

PMID- 22159157
TI  - Monitoring of potentially toxic cyanobacteria using an online multi-probe in
      drinking water sources.
AB  - Toxic cyanobacteria threaten the water quality of drinking water sources across
      the globe. Two such water bodies in Canada (a reservoir on the Yamaska River and
      a bay of Lake Champlain in Quebec) were monitored using a YSI 6600 V2-4 (YSI,
      Yellow Springs, Ohio, USA) submersible multi-probe measuring in vivo phycocyanin
      (PC) and chlorophyll-a (Chl-a) fluorescence, pH, dissolved oxygen, conductivity,
      temperature, and turbidity in parallel. The linearity of the in vivo fluorescence
      PC and Chl-a probe measurements were validated in the laboratory with Microcystis
      aeruginosa (r(2) = 0.96 and r(2) = 0.82 respectively). Under environmental
      conditions, in vivo PC fluorescence was strongly correlated with extracted PC (r
      = 0.79) while in vivo Chl-a fluorescence had a weaker relationship with extracted
      Chl-a (r = 0.23). Multiple regression analysis revealed significant correlations
      between extracted Chl-a, extracted PC and cyanobacterial biovolume and in vivo
      fluorescence parameters measured by the sensors (i.e. turbidity and pH). This
      information will help water authorities select the in vivo parameters that are
      the most useful indicators for monitoring cyanobacteria. Despite highly toxic
      cyanobacterial bloom development 10 m from the drinking water treatment plant's
      (DWTP) intake on several sampling dates, low in vivo PC fluorescence,
      cyanobacterial biovolume, and microcystin concentrations were detected in the
      plant's untreated water. The reservoir's hydrodynamics appear to have prevented
      the transport of toxins and cells into the DWTP which would have deteriorated the
      water quality. The multi-probe readings and toxin analyses provided critical
      evidence that the DWTP's untreated water was unaffected by the toxic
      cyanobacterial blooms present in its source water.

PMID- 22159159
TI  - Mutatis mutandis: harmonize the standard!

PMID- 22159160
TI  - SNM practice guideline for dopamine transporter imaging with 123I-ioflupane SPECT
      1.0.

PMID- 22159161
TI  - Molecular mechanisms of somatostatin receptor trafficking.
AB  - The neuropeptide somatostatin (SRIF) is an important modulator of
      neurotransmission in the central nervous system and acts as a potent inhibitor of
      hormone and exocrine secretion. In addition, SRIF regulates cell proliferation in
      normal and tumorous tissues. The six somatostatin receptor subtypes (sst1, sst2A,
      sst2B, sst3, sst4, and sst5), which belong to the G protein-coupled receptor
      (GPCR) family, share a common molecular topology: a hydrophobic core of seven
      transmembrane-spanning alpha-helices, three intracellular loops, three
      extracellular loops, an amino-terminus outside the cell, and a carboxyl-terminus
      inside the cell. For most of the GPCRs, intracytosolic sequences, and more
      particularly the C-terminus, are believed to interact with proteins that are
      mandatory for either exporting neosynthesized receptor, anchoring receptor at the
      plasma membrane, internalization, recycling, or degradation after ligand binding.
      Accordingly, most of the SRIF receptors can traffic not only in vitro within
      different cell types but also in vivo. A picture of the pathways and proteins
      involved in these processes is beginning to emerge.

PMID- 22159162
TI  - Electrospinning of nanofibers from non-polymeric systems: polymer-free nanofibers
      from cyclodextrin derivatives.
AB  - High molecular weight polymers and high polymer concentrations are desirable for
      the electrospinning of nanofibers since polymer chain entanglements and
      overlapping are important for uniform fiber formation. Hence, the electrospinning
      of nanofibers from non-polymeric systems such as cyclodextrins (CDs) is quite a
      challenge since CDs are cyclic oligosaccharides. Nevertheless, in this study, we
      have successfully achieved the electrospinning of nanofibers from chemically
      modified CDs without using a carrier polymer matrix. Polymer-free nanofibers were
      electrospun from three different CD derivatives, hydroxypropyl-beta-cyclodextrin
      (HPbetaCD), hydroxypropyl-gamma-cyclodextrin (HPgammaCD) and methyl-beta
      cyclodextrin (MbetaCD) in three different solvent systems, water,
      dimethylformamide (DMF) and dimethylacetamide (DMAc). We observed that the
      electrospinning of these CDs is quite similar to polymeric systems in which the
      solvent type, the solution concentration and the solution conductivity are some
      of the key factors for obtaining uniform nanofibers. Dynamic light scattering
      (DLS) measurements indicated that the presence of considerable CD aggregates and
      the very high solution viscosity were playing a key role for attaining nanofibers
      from CD derivatives without the use of any polymeric carrier. The electrospinning
      of CD solutions containing urea yielded no fibers but only beads or splashes
      since urea caused a notable destruction of the self-associated CD aggregates in
      their concentrated solutions. The structural, thermal and mechanical
      characteristics of the CD nanofibers were also investigated. Although the CD
      derivatives are amorphous small molecules, interestingly, we observed that these
      electrospun CD nanofibers/nanowebs have shown some mechanical integrity by which
      they can be easily handled and folded as a free standing material.

PMID- 22159163
TI  - The synthesis and photophysical studies of cyclometalated Pt(II) complexes with
      C,N,N-ligands containing imidazolyl donors.
AB  - Two new C,N,N-type ligands (HL(2) and HL(3)), containing a C(phenyl), a
      N(pyridyl), and a N(imidazolyl) donor, and their cycloplatinated complexes,
      [Pt(L(2))Cl] (1), [Pt(L(3))Cl] (2), [Pt(L(2))(PPh(3))](+) (3) and
      [Pt(L(3))(PPh(3))](+) (4), have been successfully synthesized and characterized.
      Spectroscopic and (3)MLCT luminescent properties of these Pt(II) cyclometalated
      complexes were found to be pH dependent. This was attributed to the
      protonation/deprotonation of the acidic 1-imidazolyl-NH moieties on the ligands.
      All the cycloplatinated complexes (both protonated and deprotonated forms)
      possessed two-photon excitability with two-photon absorption cross-sections
      ranging from 6.0 to 30.0 GM (protonated forms) and from 16.2 to 24.9 GM
      (deprotonated forms).

PMID- 22159164
TI  - Protein-based nanotubes for biomedical applications.
AB  - This review presents highlights of our latest results of studies directed at
      developing protein-based smart nanotubes for biomedical applications. These
      practical biocylinders were prepared using an alternate layer-by-layer (LbL)
      assembly of protein and oppositely charged poly(amino acid) into a nanoporous
      polycarbonate (PC) membrane (pore diameter, 400 nm), with subsequent dissolution
      of the template. The tube wall typically comprises six layers of poly-L-arginine
      (PLA) and human serum albumin (HSA) [(PLA/HSA)(3)]. The obtained (PLA/HSA)(3)
      nanotubes (NTs) can be dispersed in aqueous medium and are hydrated
      significantly. Several ligands for HSA, such as zinc(II) protoporphyrin IX
      (ZnPP), were bound to the HSA component in the cylindrical wall. Similar NTs
      comprising recombinant HSA mutant, which has a strong binding affinity for ZnPP,
      captured the ligand more tightly. The Fe(3)O(4)-coated NTs can be collected
      easily by exposure to a magnetic field. The hybrid NTs bearing a single avidin
      layer as an internal wall captured biotin-labeled nanoparticles into the central
      channel when their particle size is sufficiently small to enter the pores. The
      NTs with an antibody surface interior entrapped human hepatitis B virus with size
      selectivity. It is noteworthy that the infectious Dane particles were
      encapsulated completely into the hollows. Other HSA-based NTs having an alpha
      glucosidase inner wall hydrolysed a glucopyranoside to yield alpha-D-glucose. A
      perspective of the practical use of the protein-based NTs is also described.

PMID- 22159165
TI  - Toward Quantum-dot Cellular Automata units: thiolated-carbazole linked
      bisferrocenes.
AB  - Quantum-dot Cellular Automata (QCA) exploit quantum confinement, tunneling and
      electrostatic interaction for transistorless digital computing. Implementation at
      the molecular scale requires carefully tailored units which must obey several
      structural and functional constraints, ranging from the capability to confine
      charge efficiently on different 'quantum-dot centers'-in order to sharply encode
      the Boolean states-up to the possibility of having their state blanked out upon
      application of an external signal. In addition, the molecular units must preserve
      their geometry in the solid state, to interact electrostatically in a controlled
      way. Here, we present a novel class of organometallic molecules, 6-3,6-bis(1
      ethylferrocen)-9H-carbazol-9-yl-6-hexan-1-thiols, which are engineered to satisfy
      all such crucial requirements at once, as confirmed by electrochemistry and
      scanning tunneling microscopy measurements, and first principles density
      functional calculations.

PMID- 22159167
TI  - A pair of 3D homochiral metal-organic frameworks: spontaneous resolution, single
      crystal-to-single-crystal transformation and selective adsorption properties.
AB  - A novel achiral hexacarboxylic ligand L was synthesized. Spontaneous resolution
      occurred during the reaction of L with Eu(NO(3))(3) to produce a pair of
      enantiomers of 1a and 1b with a formula of [EuL(NO(3))(3)(H(2)O)].13H(2)O, which
      possesses 1D chiral open channels formed by triple-stranded helical chains. When
      heated to 60  degrees C, 1a releases coordinated and partial lattice H(2)O
      molecules to give a complex of [EuL(NO(3))(3)].4H(2)O (1a'), accompanied by a
      single-crystal-to-single-crystal transformation from 1a to 1a', with the space
      group changing from P2(1) to P3(1)2. The dehydrated 1 can selectively adsorb
      water over organic solvents and exhibits reversible water adsorption upon
      dehydration and hydration.

PMID- 22159168
TI  - Introduction to the themed issue on the biology of UVA.

PMID- 22159169
TI  - Three-year outcomes of the surgery for trichiasis, antibiotics to prevent
      recurrence trial.
AB  - OBJECTIVE: To determine whether treatment with oral azithromycin compared with
      topical tetracycline reduces the recurrence of trichiasis for up to 3 years
      following surgery for trichiasis. METHODS: The Surgery for Trichiasis,
      Antibiotics to Prevent Recurrence (STAR) trial is a randomized, single-masked,
      clinical trial conducted in southern Ethiopia, a region where trachoma is
      hyperendemic. A total of 1452 patients who underwent trichiasis surgery were
      randomly assigned at a 2:1 ratio to either a single dose of oral azithromycin (1
      g) or topical tetracycline (twice per day for 6 weeks) following surgery. MAIN
      OUTCOME MEASURES: Recurrence of trichiasis within 3 years following surgery.
      RESULTS: The rate of recurrence was 10% in the azithromycin group and 13% in the
      tetracycline group. The azithromycin group had a 22% reduction in recurrence of
      trichiasis 3 years after surgery compared with the tetracycline group (P = .13).
      Severity of entropion at baseline was the most significant predictor of
      recurrence of trichiasis at 3 years. CONCLUSION: Trichiasis recurrence rates in
      the STAR trial remained low for up to 3 years following surgery. The protective
      effect of a single dose of azithromycin was less than at 1 year and, although not
      statistically significant, was still suggestive up to 3 years following
      trichiasis surgery. APPLICATION TO CLINICAL PRACTICE: A single dose of
      azithromycin after surgery remains an integral component of the World Health
      Organization's strategy for the elimination of trachoma by the year 2020.

PMID- 22159170
TI  - Comparison of screening procedures in hydroxychloroquine toxicity.
AB  - OBJECTIVES: To compare different screening procedures for hydroxychloroquine
      sulfate (Plaquenil) toxicity at different stages of damage. METHODS: Ten patients
      were studied using 10-2 automated fields, multifocal electroretinography,
      spectral domain optical coherence tomography (SD-OCT), and fundus
      autofluorescence. RESULTS: All 10 patients used hydroxychloroquine for more than
      6 years, and those with severe toxicity had been overdosed. Fundus examination
      findings were normal except for the patients with severe toxicity. All the
      patients showed parafoveal field loss, but this was sometimes subtle. Multifocal
      electroretinography demonstrated parafoveal weakness in the milder cases. The SD
      OCT subfield thickness plots showed a ring of parafoveal thinning in all the
      patients. The SD-OCT cross-sections showed parafoveal loss of the inner segment
      outer segment and cone outer segment tip lines at early stages of toxicity,
      progressing to parafoveal thinning of the outer nuclear layer and eventually to
      retinal pigment epithelium damage. There was a ring of autofluorescence in most
      patients. CONCLUSIONS: Overdosage with hydroxychloroquine seemed a significant
      risk factor for toxicity. Different individuals were more or less sensitive to
      different tests. Fields can be sensitive but only if read with a low threshold
      for change. Hydroxychloroquine causes early parafoveal loss of the outer segment
      lines on SD-OCT, with the first changes often evident in the inferotemporal
      quadrant. Parafoveal thinning of the outer nuclear layer follows, before retinal
      pigment epithelium damage is visible. Careful screening with multiple tests can
      detect toxic damage before prominent loss of the outer nuclear layer.

PMID- 22159171
TI  - Prevalence of and risk factors for age-related macular degeneration in a
      multiethnic Asian cohort.
AB  - OBJECTIVE: To describe the prevalence of and risk factors for age-related macular
      degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian
      persons. METHODS: In this population-based study, 3172 persons of Chinese, Malay,
      and Indian ethnicities 40 years and older were included. Participants underwent
      comprehensive systemic and ocular examination, retinal photography, and
      laboratory investigations. Early and late AMD signs were graded from retinal
      photographs. Age-standardized prevalence estimates were calculated using the 2010
      Singapore adult population as the standard population. Association with a range
      of systemic risk factors was analyzed. RESULTS: Of 3172 participants, AMD was
      present in 211 subjects. Age-standardized prevalence of AMD was 7.0% in persons
      40 years and older. The age-standardized prevalence was similar in all 3 Asian
      ethnic groups: Chinese, 7.3%; Malay, 7.7%; and Indian, 5.7% (P value = .44). The
      prevalence increased with age and was higher in men. Of the range of risk factors
      evaluated, only myopic refractive error (<-0.5 D) was significantly associated
      with a lower risk for AMD (odds ratio, 0.44; P < .001, compared with emmetropia)
      in Chinese men. CONCLUSIONS: The prevalence of AMD was similar in the 3 major
      ethnic groups in Asia and comparable with white populations. Myopic refractive
      error was associated with reduced risk of AMD in Chinese men.

PMID- 22159172
TI  - Characterization of limbal stem cell deficiency by in vivo laser scanning
      confocal microscopy: a microstructural approach.
AB  - OBJECTIVE: To evaluate the cellular changes in the corneal epithelium and
      surrounding structures in limbal stem cell deficiency (LSCD) by using in vivo
      laser scanning confocal microscopy. METHODS: This was a prospective comparative
      study that included 27 eyes of 20 patients with LSCD and 12 eyes of 10 healthy
      subjects. All subjects underwent slitlamp examination, and LSCD was classified
      into 3 groups on the basis of clinical presentation. Confocal imaging of the
      central cornea and 4 locations of limbus was performed. Morphologic
      characteristics of the corneal epithelium were studied. The basal epithelial cell
      density and subbasal nerve density in the central cornea were calculated, and a
      potential correlation between the decrease in basal epithelial cell density and
      subbasal nerve density in LSCD was investigated. RESULTS: The wing and basal
      epithelial cells became progressively metaplastic, and the basal epithelial cell
      density and subbasal nerve density in the early and intermittent stages decreased
      significantly compared with controls (all P < .01). Normal basal epithelial cell
      morphology was completely lost and subbasal nerves were absent in the late stage
      of LSCD. The decrease in basal cell density correlated with the decrease in
      subbasal nerve density in patients with LSCD (P = .03). CONCLUSIONS: There are
      significant microstructural changes associated with early LSCD. These cellular
      changes could help to understand the disease process and classify and monitor
      limbal stem cell dysfunction.

PMID- 22159174
TI  - Enhanced upconversion emission in Yb3+ and Er3+ codoped NaGdF4 nanocrystals by
      introducing Li+ ions.
AB  - beta-NaGdF(4) : Yb(3+)/Er(3+) nanoparticles (NPs) codoped with Li(+) ions were
      prepared for the first time via a thermal decomposition reaction of
      trifluoroacetates in oleylamine. The influence of site occupancy of Li(+) on the
      upconversion emission of beta-NaGdF(4) : Yb(3+)/Er(3+) NPs was investigated in
      detail. The upconversion emission intensity was significantly enhanced by
      introducing different concentrations of Li(+) ions. In contrast to lithium-free
      beta-NaGdF(4) : Yb(3+)/Er(3+), the green and red UC emission intensities of the
      NPs codoped with 7 mol% Li(+) ions were enhanced by about 47 and 23 times,
      respectively. The luminescence enhancement should be attributed to the distortion
      of the local asymmetry around Er(3+) ions. The mechanisms for the enhancement of
      upconversion emission were discussed. In addition, it was found in our research
      work that beta-NaGdF(4) : Yb(3+)/Er(3+) NPs exhibited paramagnetic features at
      room temperature and the magnetization was slightly increased by introducing
      Li(+) ions.

PMID- 22159175
TI  - A solid molecular basket sorbent for CO2 capture from gas streams with low CO2
      concentration under ambient conditions.
AB  - In this paper, a solid molecular basket sorbent, 50 wt% PEI/SBA-15, was studied
      for CO(2) capture from gas streams with low CO(2) concentration under ambient
      conditions. The sorbent was able to effectively and selectively capture CO(2)
      from a gas stream containing 1% CO(2) at 75  degrees C, with a breakthrough and
      saturation capacity of 63.1 and 66.7 mg g(-1), respectively, and a selectivity of
      14 for CO(2)/CO and 185 for CO(2)/Ar. The sorption performance of the sorbent was
      influenced greatly by the operating temperature. The CO(2)-TPD study showed that
      the sorbent could be regenerated under mild conditions (50-110  degrees C) and
      was stable in the cyclic operations for at least 20 cycles. Furthermore, the
      possibility for CO(2) capture from air using the PEI/SBA-15 sorbent was studied
      by FTIR and proved by TPD. A capacity of 22.5 mg g(-1) was attained at 75 
      degrees C via a TPD method using a simulated air with 400 ppmv CO(2) in N(2).

PMID- 22159176
TI  - Non-enzymatic electrochemical detection of glycerol on boron-doped diamond
      electrode.
AB  - A non-enzymatic direct electrochemical glycerol detection method at a commercial
      boron-doped diamond (BDD) electrode in 0.1 M NaOH supporting electrolyte was
      developed. All the used electrochemical techniques proved useful features for the
      oxidation and direct amperometric determination of glycerol at a BDD electrode in
      0.1 M NaOH aqueous solution. It was found that the direct electrooxidation of
      glycerol on the BDD electrode requires both adsorbed glycerol and hydroxyls at
      the electrode surface. Also, the sp(2) carbon did not allow enhancement of the
      glycerol oxidation process. The electronalytical sensitivity for the
      determination of glycerol at the BDD electrode ranged from 0.040 to 0.226 MUA mM(
      1) as a function of the technique used. The highest electroanalytical sensitivity
      for the determination of glycerol at the BDD electrode was reached in batch
      system amperometric quantification under stirring conditions. Performed recovery
      studies indicated that it is possible to determine glycerol in real samples, and
      the proposed batch system analysis-based methodology can be a valuable tool for
      practical glycerol analysis.

PMID- 22159177
TI  - Structure, bonding, electronic and energy aspects of a new family of early
      lanthanide (La, Ce and Nd) complexes with phosphoric triamides: insights from
      experimental and DFT studies.
AB  - A new family of isostructural early lanthanide(III) complexes (LnXPA) of the
      general formula Ln(XPA)(2)Cl(3)(solv)(2), where Ln = La, Ce and Nd, XPA = (4-X
      C(6)H(4)NH)P(O)(NC(4)H(8)O)(2), X = H, F, Cl and Br, and solv = H(2)O and
      CH(3)OH, is introduced. X-ray crystallography shows that the replacement of the
      coordinated water by a methanol molecule may reduce the symmetry level of the
      unit cell from the orthorhombic crystal system and the space group Fdd2 to
      monoclinic and C2/c. DFT calculations, at B3LYP, PBE and B3PW91 levels, have been
      carried out to get a better insight into the structural, electronic and energy
      aspects of the compounds. The large cation attraction energy (-DeltaE) values in
      the range 269-273 kcal mol(-1), at the B3PW91/ECP/6-311+G** level for the model
      complexes XPA-La(3+) with stoichiometry 1 : 1, represent new ligands XPA as
      efficient complexant agents for lanthanides. The electronic nature of para
      substituent X has no significant effect on the Ln-ligand bonding and cation
      affinity of the ligands XPA. The results of atoms in molecules (AIM) analysis
      reveal a partial covalent contribution of the Ln-ligand interaction for the
      models XPA-La(3+) in the absence of counterions and coordinated solvents. In the
      real complexes LnXPA, a closed-shell Ln-ligand interaction is established.
      Increasing the charge difference between nitrogen and phosphorus atoms (by ~0.06
      e) associated with a weakening of the Lp(O(P))->sigma*(P-N) electronic
      delocalization (Lp(O(P)) being the lone pair of the phosphoryl oxygen atom) may
      lead to an increase in partial multiple bond character of the P-N bonds in
      coordinated ligands, agreeing with the increase in nu(P-N) and (2)J(PH) coupling
      constant values. The changes in electron density (rho) and electronic energy
      density (H(r)) values confirm these structural reorganizations upon complexation.

PMID- 22159178
TI  - Synthesis of bimetallic Pt-Pd core-shell nanocrystals and their high
      electrocatalytic activity modulated by Pd shell thickness.
AB  - Bimetallic Pt-Pd core-shell nanocrystals (NCs) are synthesized through a two-step
      process with controlled Pd thickness from sub-monolayer to multiple atomic
      layers. The oxygen reduction reaction (ORR) catalytic activity and methanol
      oxidation reactivity of the core-shell NCs for fuel cell applications in alkaline
      solution are systematically studied and compared based on different Pd thickness.
      It is found that the Pd shell helps to reduce the over-potential of ORR by up to
      50 mV when compared to commercial Pd black, while generating up to 3-fold higher
      kinetic current density. The carbon monoxide poisoning test shows that the
      bimetallic NCs are more resistant to the CO poisoning than Pt NCs and Pt black.
      It is also demonstrated that the bimetallic Pt-Pd core-shell NCs can enhance the
      current density of the methanol oxidation reaction, lowering the over-potential
      by 35 mV with respect to the Pt core NCs. Further investigation reveals that the
      Pd/Pt ratio of 1/3, which corresponds to nearly monolayer Pd deposition on Pt
      core NCs, gives the highest oxidation current density and lowest over-potential.
      This study shows for the first time the systematic investigation of effects of Pd
      atomic shells on Pt-Pd bimetallic nanocatalysts, providing valuable guidelines
      for designing high-performance catalysts for fuel cell applications.

PMID- 22159173
TI  - Evaluation of visual acuity measurements after autorefraction vs manual
      refraction in eyes with and without diabetic macular edema.
AB  - OBJECTIVE: To compare visual acuity (VA) scores after autorefraction vs manual
      refraction in eyes of patients with diabetes mellitus and a wide range of VAs.
      METHODS: The letter score from the Electronic Visual Acuity (EVA) test from the
      electronic Early Treatment Diabetic Retinopathy Study was measured after
      autorefraction (AR-EVA score) and after manual refraction (MR-EVA score), which
      is the research protocol of the Diabetic Retinopathy Clinical Research Network.
      Testing order was randomized, study participants and VA examiners were masked to
      refraction source, and a second EVA test using an identical supplemental manual
      refraction (MR-EVAsuppl score) was performed to determine test-retest
      variability. RESULTS: In 878 eyes of 456 study participants, the median MR-EVA
      score was 74 (Snellen equivalent, approximately 20/32). The spherical equivalent
      was often similar for manual refraction and autorefraction (median difference,
      0.00; 5th-95th percentile range, -1.75 to 1.13 diopters). However, on average,
      the MR-EVA scores were slightly better than the AR-EVA scores, across the entire
      VA range. Furthermore, the variability between the AR-EVA scores and the MR-EVA
      scores was substantially greater than the test-retest variability of the MR-EVA
      scores (P < .001). The variability of differences was highly dependent on the
      autorefractor model. CONCLUSIONS: Across a wide range of VAs at multiple sites
      using a variety of autorefractors, VA measurements tend to be worse with
      autorefraction than manual refraction. Differences between individual
      autorefractor models were identified. However, even among autorefractor models
      that compare most favorably with manual refraction, VA variability between
      autorefraction and manual refraction is higher than the test-retest variability
      of manual refraction. The results suggest that, with current instruments,
      autorefraction is not an acceptable substitute for manual refraction for most
      clinical trials with primary outcomes dependent on best-corrected VA.

PMID- 22159179
TI  - Dosimetric analysis of 177Lu-cG250 radioimmunotherapy in renal cell carcinoma
      patients: correlation with myelotoxicity and pretherapeutic absorbed dose
      predictions based on 111In-cG250 imaging.
AB  - This study aimed to estimate the radiation absorbed doses to normal tissues and
      tumor lesions during radioimmunotherapy with (177)Lu-cG250. Serial planar
      scintigrams after injection of (111)In-cG250 or (177)Lu-cG250 in patients with
      metastasized renal cell carcinoma were analyzed quantitatively. The estimated
      radiation doses were correlated with observed hematologic toxicity. In addition,
      the accuracy of the predicted therapeutic absorbed doses, based on diagnostic
      (111)In-cG250 data, were determined. METHODS: Twenty patients received a
      diagnostic tracer activity of (111)In-cG250 (185 MBq), followed by
      radioimmunotherapy with (177)Lu-cG250. The administered activity of (177)Lu-cG250
      was escalated by entering 3 patients at each activity level starting at 1,110
      MBq/m(2), with increments of 370 MBq/m(2). After each diagnostic and therapeutic
      administration, whole-body scintigraphic images and pharmacokinetic data were
      acquired. Hematologic toxicity was graded using the Common Toxicity Criteria,
      version 3.0. Diagnostic (111)In-cG250 data were used to simulate (177)Lu and
      (90)Y data by correcting for the difference in physical decay. Absorbed doses
      were calculated for the whole body, red marrow, organs, and tumor metastases for
      the therapeutic (177)Lu-cG250, simulated (177)Lu-cG250, and simulated (90)Y-cG250
      data. RESULTS: Observed hematologic toxicity, especially platelet toxicity,
      correlated significantly with the administered activity (r = 0.85), whole-body
      absorbed dose (r = 0.65), and red marrow dose (r = 0.62 and 0.75). An inverse
      relationship between the mass and absorbed dose of the tumor lesions was
      observed. Calculated mean absorbed doses were similar for the simulated and
      measured (177)Lu-cG250 data. Absorbed doses (whole body and red marrow) based on
      the simulated (177)Lu-cG250 data correlated with the observed platelet toxicity
      (r = 0.65 and 0.82). The tumor-to-red marrow dose ratio was higher for
      radioimmunotherapy with (177)Lu-cG250 than for radioimmunotherapy with (90)Y
      cG250, indicating that (177)Lu has a wider therapeutic window for
      radioimmunotherapy with cG250 than (90)Y. CONCLUSION: In patients with
      metastasized renal cell carcinoma, hematologic toxicity after treatment with
      (177)Lu-cG250 can be predicted on the basis of administered activity and whole
      body and red marrow-absorbed dose. Diagnostic (111)In-cG250 data can be used to
      accurately predict absorbed doses and myelotoxicity of radioimmunotherapy with
      (177)Lu-cG250. These estimations indicate that in these patients, higher
      radiation doses can be guided to the tumors with (177)Lu-cG250 than with (90)Y
      cG250.

PMID- 22159182
TI  - Synthesis, purification, and characterization of phosphine oxides and their
      hydrogen peroxide adducts.
AB  - Reactions of the tertiary phosphines R(3)P (R = Me, Bu, Oct, Cy, Ph) with 35%
      aqueous H(2)O(2) gives the corresponding oxides as the H(2)O(2) adducts
      R(3)P=O.(H(2)O(2))(x) (x = 0.5-1.0). Air oxidation leads to a mixture of products
      due to the insertion of oxygen into one or more P-C bonds. (31)P NMR spectroscopy
      in solution and in the solid state, as well as IR spectroscopy reveal distinct
      features of the phosphine oxides as compared to their H(2)O(2) adducts. The
      single crystal X-ray analyses of Bu(3)P=O and [Cy(3)P=O.(H(2)O(2))](2) show a P=O
      stacking motif for the phosphine oxide and a cyclic structure, in which the six
      oxygen atoms exhibit a chair conformation for the dimeric H(2)O(2) adduct.
      Different methods for the decomposition of the bound H(2)O(2) and the removal of
      the ensuing strongly adsorbed H(2)O are evaluated. Treating R(3)P=O.(H(2)O(2))(x)
      with molecular sieves destroys the bound H(2)O(2) safely under mild conditions
      (room temperature, toluene) within one hour and quantitatively removes the
      adsorbed H(2)O from the hygroscopic phosphine oxides within four hours. At 60 
      degrees C the entire decomposition/drying process is complete within one hour.

PMID- 22159181
TI  - Impact of myocardial scarring on outcomes of cardiac resynchronization therapy:
      extent or location?
AB  - Refining the criteria for patient selection for cardiac resynchronization therapy
      (CRT) may improve its outcomes. The study objective was to determine the effect
      of scar location, scar burden, and left ventricular (LV) lead position on CRT
      outcomes. METHODS: The study included 213 consecutive CRT recipients with
      radionuclide myocardial perfusion imaging before CRT between January 2002 and
      December 2008. Scar localization and myocardial viability were analyzed using a
      17-segment model and a 5-point semiquantitative scale. New York Heart Association
      (NYHA) class and echocardiography were assessed before and after CRT. The
      anatomic LV lead location in the 17-segment model was assessed by review of
      fluoroscopic cinegrams in right and left anterior oblique views. As in published
      studies, clinical response was defined as an absolute improvement in LV ejection
      fraction of >=5 percentage points after CRT. RESULTS: A total of 651 scar
      segments was identified in 213 patients. Eighty-three percent of scar segments
      were located in the LV anterior, posterior, septal, and apical regions, whereas
      84% of LV leads were in the lateral wall. Only 11% of LV leads were positioned in
      scar segments. The extent of scarring was significantly higher in nonresponders
      than in responders (18.0% vs. 6%, P = 0.001). Compared with patients with
      scarring >22%, patients <=70 y with scarring <=22% of the left ventricle had a
      greater increase in LV ejection fraction (10.1% +/- 10.5% vs. 0.8% +/- 6.1%; P <
      0.001) and improvement in NYHA class (-0.9 +/- 0.7 vs. -0.5 +/- 0.8; P = 0.02).
      CONCLUSION: LV leads were often located in viable myocardial regions. Less scar
      burden was associated with a greater improvement in heart failure but only in
      relatively younger CRT recipients.

PMID- 22159180
TI  - 3'-deoxy-3'-18F-fluorothymidine PET and MRI for early survival predictions in
      patients with recurrent malignant glioma treated with bevacizumab.
AB  - With the dismal prognosis for malignant glioma patients, survival predictions
      become key elements in patient management. This study compares the value of 3'
      deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET and MRI for early outcome
      predictions in patients with recurrent malignant glioma on bevacizumab therapy.
      METHODS: Thirty patients treated with bevacizumab combination therapy underwent
      (18)F-FLT PET immediately before and at 2 and 6 wk after the start of treatment.
      A metabolic treatment response was defined as a decrease of equal to or greater
      than 25% in tumor (18)F-FLT uptake (standardized uptake values) from baseline
      using receiver-operating-characteristic analysis. MRI treatment response was
      assessed at 6 wk according to the Response Assessment in Neurooncology criteria.
      (18)F-FLT responses at different times were compared with MRI response and
      correlated with progression-free survival and overall survival using Kaplan-Meier
      analysis. Metabolic response based on (18)F-FLT was further compared with other
      outcome predictors using Cox regression analysis. RESULTS: Early and late changes
      in tumor (18)F-FLT uptake were more predictive of overall survival than MRI
      criteria (P < 0.001 and P = 0.01, respectively). (18)F-FLT uptake changes were
      also predictive of progression-free survival (P < 0.001). The median overall
      survival for responders was 3.3 times longer than for nonresponders based on
      (18)F-FLT PET criteria (12.5 vs. 3.8 mo, P < 0.001) but only 1.4 times longer
      using MRI assessment (12.9 vs. 9.0 mo, P = 0.05). On the basis of the 6-wk (18)F
      FLT PET response, there were 16 responders (53%) and 14 nonresponders (47%),
      whereas MRI identified 9 responders (7 partial response, 2 complete response,
      31%) and 20 nonresponders (13 stable disease, 7 progressive disease, 69%). In 7
      of the 8 discrepant cases between MRI and PET, (18)F-FLT PET was able to
      demonstrate response earlier than MRI. Among various outcome predictors,
      multivariate analysis identified (18)F-FLT PET changes at 6 wk as the strongest
      independent survival predictor (P < 0.001; hazard ratio, 10.051). CONCLUSION:
      Changes in tumor (18)F-FLT uptake were highly predictive of progression-free and
      overall survival in patients with recurrent malignant glioma on bevacizumab
      therapy. (18)F-FLT PET seems to be more predictive than MRI for early treatment
      response.

PMID- 22159183
TI  - High-density metallic nanogaps fabricated on solid substrates used for surface
      enhanced Raman scattering.
AB  - The Raman signal of adsorbed molecules can be significantly enhanced by utilizing
      metallic structures with high-density Raman hot spots used as surface enhanced
      Raman scattering (SERS) substrates. In this work, we develop a simple, convenient
      and tunable method to fabricate high-density Ag or Au nanogaps on Si wafers.
      These nanogaps can serve as Raman hot spots, leading to dramatic enhancement of
      the Raman signal. The high-density nanogaps can be formed by repeating the
      electroless deposition of Ag NPs (or Au NPs) and coating of p-aminothiophenol
      (PATP, a Raman probe) on the deposited Ag NPs (or Au NPs) through the self
      assembly process. After removal of PATP by O(2) plasma, the as-fabricated SERS
      substrate can be reused for the detection of other molecules.

PMID- 22159184
TI  - DNA quantification via traceable phosphorus measurement through microwave
      assisted UV digestion-ion chromatography.
AB  - Accurate quantification of deoxyribonucleic acid (DNA) is critical for many
      analyses in molecular biology and genetic tests. We present a method in which the
      stoichiometrically existing phosphorus content in purified genomic DNA is
      quantitatively converted into orthophosphate ions by microwave assisted-UV
      digestion in the presence of microlitre quantities of dilute reagents (HCl,
      HNO(3), H(2)O(2)). The tandem use of microwave energy and ultraviolet photons for
      DNA digestion in pressurized quartz vessels enables a maximum reaction
      temperature of 240  degrees C resulting in efficient and fast mineralization of
      high molecular weight DNA within 30 minutes. Compared to hotplate digestion, the
      digestion time is reduced by a factor of 32. The MW-UV sample preparation
      approach coupled with the ion chromatographic measurement of phosphate using a
      high performance (HP) methodology provides an accurate quantitation of phosphorus
      mass fractions as low as 0.3 MUg g(-1), corresponding to a DNA mass of 25 MUg.
      The relative expanded uncertainties (% U) expressed at 95% confidence for these
      analyses range from 0.2 to 0.6%. Critically, the matrix of the calibrant solution
      is also matched with respect to the digested matrix anions (chloride, nitrate),
      without which significant bias in IC performance is observed. The phosphorus
      content of the calf thymus DNA was also measured using high-performance
      inductively coupled plasma optical emission spectroscopy (HP-ICP-OES), which
      provided independent data for comparison with the MW-UV digestion-IC based
      approach. Ion chromatography requires smaller volume of materials to perform the
      analysis and could be useful for characterizing primary calibration standards and
      certified reference materials with low uncertainties.

PMID- 22159185
TI  - A bottom-up valence bond derivation of excitation energies in 1D-like delocalized
      systems.
AB  - Using the chemically relevant parameters hopping integral t(0) and on-site
      repulsion energy U, the charge gap (lowest dipolarly allowed transition energy)
      in 1D systems is examined through a bottom-up strategy. The method is based on
      the locally ionized states, the energies of which are corrected using short-range
      delocalization effects. In a valence bond framework, these states interact to
      produce an excitonic matrix which accounts for the delocalized character of
      excited states. The treatment, which gives access to the correlated spectrum of
      ionization potentials, is entirely analytical and valid whatever the U/|t(0)|
      ratio for such systems ruled by Peierls-Hubbard Hamiltonians. This second-order
      analytical derivation is finally confronted to numerical results of a
      renormalized excitonic treatment using larger blocks as functions of the U/|t(0)|
      ratio. The method is applied to dimerized chains and to fused polybenzenic 1D
      lattices. Such approaches complement the traditional Bloch-function based picture
      and deliver a conceptual understanding of the charge gap opening process based on
      a chemical intuitive picture.

PMID- 22159186
TI  - Efficient synthetic method for the preparation of allyl- and propargyl-epoxides
      by allylation and propargylation of alpha-haloketones with organozinc reagents.
AB  - A simple, efficient, and non-metal catalyzed synthetic method for the preparation
      of substituted allyl- and propargyl-epoxides by allylation and propargylation of
      alpha-halo ketones with organozinc reagents in mild conditions is reported in
      this paper. The present method complements the existing synthetic methods due to
      some advantageous properties of the organozinc reagents such as availability,
      selectivity, operational simplicity and low toxicity.

PMID- 22159187
TI  - Synthesis of ureas from titanium imido complexes using CO2 as a C-1 reagent at
      ambient temperature and pressure.
AB  - The coordinatively unsaturated 12-electron complex dichloro t-butylimido
      bispyridine titanium(IV) (2a) has been shown to react with CO(2) to give N,N-bis
      t-butyl urea. Two analogous sterically hindered coordinatively saturated 14
      electron complexes dichloro t-butylimido trispyridine titanium(IV) (10a) and
      dichloro 2,6-(i-Pr)(2)phenylimido trispyridine titanium(IV) (10b) also gave their
      corresponding symmetrical ureas upon treatment with CO(2). Further experiments
      support the intermediary of metallocycles formed from heterocumulene metathesis
      reactions. The unsymmetrical urea N-benzyl, N-t-butyl urea (11) was produced from
      treatment of 2,6-(i-Pr)(2)phenylimido trispyridine titanium(IV) (10b) with CO(2)
      and interception with BnNH(2). Equimolar quantities of N,N
      bistrimethylsilybenzylamine or N,N-bistrimethylsilyphenethylamine were shown to
      promote the reaction between t-butylimido bispyridine titanium(IV) (2a) and CO(2)
      to give near quantitative yields of symmetrical urea. Other symmetrical ureas
      could be produced from TiCl(4), amine and CO(2) in moderate to quantitative
      yields depending on the stoichiometry of amine present.

PMID- 22159188
TI  - Facile in situ fabrication of graphene-upconversion hybrid materials with
      amplified electrogenerated chemiluminescence.
AB  - A simple and general synthetic approach for one-step creation of graphene
      upconversion nanocomposite by an in situ hydrothermal method has been developed.
      Using graphene oxide (GO) as a precursor reagent, the reduction of GO and the
      deposition of NaYF(4)/Yb,Er on graphene occur simultaneously. The
      electrogenerated chemiluminescent intensity of NaYF(4)/Yb,Er is significantly
      amplified by graphene due to its wonderful conductivity, extraordinary electron
      transport properties and large specific surface area.

PMID- 22159189
TI  - Determination of L- and D-fucose using amperometric electrodes based on diamond
      paste.
AB  - Monocrystalline diamond (natural diamond, synthetic-1 and synthetic-2) based
      electrochemical electrodes were designed for the analysis of L- and D-fucose.
      Response characteristics of the electrochemical electrodes were determined using
      cyclic voltammetry and differential pulse voltammetry (DPV). L-fucose was
      determined using DPV with electrodes based on natural diamond, synthetic-1 and
      synthetic-2, respectively, at 240 mV using NaCl as the electrolyte (pH 3.0); at
      160 mV using KNO(3) (pH 10.0) and at 80 mV using KCl as the electrolyte (pH 10.0)
      while D-fucose was analyzed at 120 mV using KCl as the electrolyte (pH 1.0); at
      140 mV using KNO(3) as the electrolyte (pH 1.0) and at 160 mV using NaNO(3) as
      the electrolyte (pH 3.0). The linear concentration ranges for L-fucose were
      between 10(-13) and 10(-9) mol L(-1) (natural diamond), 10(-11) and 10(-8) mol L(
      1) (synthetic-1) and 10(-6) and 10(-3) mol L(-1) (synthetic-2) with detection
      limits of 10(-14), 10(-12) and 10(-8) mol L(-1) magnitude order, respectively.
      For D-fucose, the linear concentration ranges were 10(-6) to 10(-3) mol L(-1)
      (natural diamond), 10(-5) to 10(-3) mol L(-1) (synthetic-1) and 10(-9) to 10(-3)
      mol L(-1) (synthetic-2) with detection limits of 10(-7), 10(-7) and 10(-10) mol
      L(-1) magnitude order, respectively. The sensors were used for the assay of L
      fucose in serum and urine samples.

PMID- 22159190
TI  - Synthesis, characterization and application of enrofloxacin complexes as thermal
      stabilizers for rigid poly(vinyl chloride).
AB  - Synthesis and characterization of both binary Co(II)- (1), Ni(II)- (2) complexes
      with enrofloxacin drug (HL(1)) and ternary Co(II)- (3), Ni(II)- (4) complexes in
      presence of DL-alanine (H(2)L(2)) are reported using physico-chemical techniques.
      The antimicrobial activity of these complexes has been screened against two gram
      positive and two gram-negative bacteria. Antifungal activity against two
      different fungi has been evaluated and compared with reference drug. All the
      binary and ternary complexes showed remarkable potential antimicrobial activity
      higher than the recommended standard agents. Ni(II)-complexes exhibited higher
      potency as compared to the parent drug against bacterial and fungal strain. In
      addition, it was of interest to investigate the reported complexes as thermal
      stabilizers and co-stabilizers for rigid PVC in air at 180  degrees C. Their high
      stabilizing efficiency is detected by their high induction period values (T(s))
      compared with some of the common reference stabilizers used industrially, such as
      dibasic lead carbonate (DBLC) and calcium-zinc soap. Blending these complexes
      with some of the reference stabilizers in different ratios had a synergistic
      effect on both induction period as it gave better thermal stability and lower
      extent of discoloration. The stabilizing efficiency is attributed at least
      partially to the ability of the metal complex stabilizer to be incorporated in
      the polymeric chains, thus disrupting the chain degradation and replace the
      labile chlorine atoms on PVC chains by a relatively more s moiety of the
      inorganic stabilizer. Their amenability to use as a biomedical additives for PVC,
      has afforded them great potential for various medical applications.

PMID- 22159191
TI  - Assembling nanoparticle coatings to improve the drug delivery performance of
      lipid based colloids.
AB  - Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug
      delivery systems, but often suffer from physical instabilities and non-ideal drug
      encapsulation and delivery performance. We review the application of engineered
      nanoparticle layers at the interface of lipid colloids to improve their
      performance as drug delivery systems. In addition we focus on the creation of
      novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their
      drug delivery applications. Specifically, nanoparticle layers can be engineered
      to enhance the physical stability of submicron lipid emulsions and liposomes,
      satbilise encapsulated active ingredients against chemical degradation, control
      molecular transport and improve the dermal and oral delivery characteristics,
      i.e. increase absorption, bioavailability and facilitate targeted delivery. It is
      feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids
      are effective encapsulation and delivery systems for both poorly soluble drugs
      and biological drugs and may form the basis for the next generation of medicines.
      Additional pre-clinical research including specific animal model studies are
      required to advance the peptide/protein delivery systems, whereas the silica
      lipid hybrid systems have now entered human clinical trials for poorly soluble
      drugs.

PMID- 22159192
TI  - Multicolor core/shell silica nanoparticles for in vivo and ex vivo imaging.
AB  - Biocompatible highly bright silica nanoparticles were designed, prepared and
      tested in small living organisms for both in vivo and ex vivo imaging. The
      results that we report here demonstrate that they are suitable for optical
      imaging applications as a possible alternative to commercially available
      fluorescent materials including quantum dots. Moreover, the tunability of their
      photophysical properties, which was enhanced by the use of different dyes as
      doping agents, constitutes a very important added value in the field of medical
      diagnostics.

PMID- 22159193
TI  - Lewis acid promoted intramolecular (3 + 2) 'cycloadditions' of
      methyleneaziridines with alkene and alkyne acceptors.
AB  - 2-Methyleneaziridines can be tethered to a variety of alkene or alkyne acceptors
      through the saturated carbon of the heterocyclic ring by application of a simple
      lithiation/alkylation sequence (8 examples, 31-59%). Treatment of the resultant
      alkene bearing substrates with BF(3).OEt(2) leads to cis
      octahydrocyclopenta[c]pyrroles in which up to four contiguous stereocentres are
      created in a diastereocontrolled manner after reductive work-up. Using an alkyne
      based substrate, a 2,4,5,6-tetrahydrocyclopenta[c]pyrrole is produced by rapid
      tautomerisation of the initially formed bisenamine. Evidence that these (3 + 2)
      'cycloadditions' proceed in a stepwise manner via a 2-aminoallyl cation is
      presented.

PMID- 22159194
TI  - Metal-organic frameworks for reverse-phase high-performance liquid
      chromatography.
AB  - Metal-organic framework MIL-53(Al) is explored for reverse-phase high-performance
      liquid chromatographic separation of a wide range of analytes from non-polar to
      polar, and acidic to basic solutes with high resolution, good selectivity,
      stability and reproducibility.

PMID- 22159211
TI  - Ruthenium complexes containing bis-benzimidazole derivatives as a new class of
      apoptosis inducers.
AB  - A series of ruthenium complexes containing bis-benzimidazole derivatives have
      been synthesized and identified as able to target mitochondria and induce caspase
      dependent apoptosis in cancer cells through superoxide overproduction.

PMID- 22159212
TI  - A spectroscopic off-on probe for simple and sensitive detection of
      carboxylesterase activity and its application to cell imaging.
AB  - A new resorufin-based spectroscopic probe, 7-(p-acetoxyphenylmethyloxy)-3H
      phenoxazin-3-one (1), has been developed for detecting carboxylesterase activity.
      The probe is designed by introducing p-acetoxyphenylmethyloxy as a bifunctional
      moiety to resorufin. The p-acetoxyphenylmethyloxy moiety not only quenches the
      spectroscopic signal of resorufin, but also serves as a recognition unit for
      carboxylesterase. As a result, the prepared latent spectroscopic probe 1 shows
      very low background signal, which is rather desired for achieving sensitive
      detection. The specific cleavage of the carboxylic ester bond by carboxylesterase
      induces the hydrolysis of the probe, resulting in the release of resorufin and
      thereby the recovery of both color and fluorescence signal. This behaviour leads
      to the development of a simple and sensitive fluorescent method for assaying
      carboxylesterase activity, with a detection limit of 8.6 * 10(-5) U mL(-1), which
      is much more sensitive than the existing fluorescence approaches. Moreover,
      experimental results showed that the probe 1 is cell membrane permeable, and its
      applicability has been demonstrated for monitoring carboxylesterase activity in
      HeLa cells.

PMID- 22159213
TI  - Aggregation kinetics and gel formation in modestly concentrated suspensions of
      oppositely charged model ceramic colloids: a numerical study.
AB  - Aggregation kinetics and gel formation in aqueous suspensions that undergo
      heteroaggregation are studied by means of Brownian dynamics simulations. The
      simulated system, described in a previous paper [M. A. Piechowiak, A. Videcoq, F.
      Rossignol, C. Pagnoux, C. Carrion, M. Cerbelaud, R. Ferrando, Langmuir, 2010,
      26(15), 12540-12547.], is constituted of two kinds of synthesized, almost equally
      sized colloids: silica particles that are negatively charged and alumina-coated
      silica particles that are positively charged. The interactions between colloids
      are modeled by the DLVO potential. Several compositions are analyzed, from silica
      rich to alumina-rich cases. The particle volume fraction phi is varied in the
      range 6-12%. The study of the aggregation kinetics allows us to clarify the
      effect of those variations on the clustering process. Gelation is analyzed by
      detection of spanning clusters in each x-, y-, z-direction of the cubic
      simulation box. Percolating networks start to be observed from phi = 7%, a low
      value of the volume fraction close to the solid volume fraction experimentally
      measured in sediments of those suspensions.

PMID- 22159214
TI  - Synthesis and oligomerization of Fmoc/Boc-protected PNA monomers of 2,6
      diaminopurine, 2-aminopurine and thymine.
AB  - A Boc-protecting group strategy for Fmoc-based PNA (peptide nucleic acid)
      oligomerization has been developed for thymine, 2,6-diaminopurine (DAP) and 2
      aminopurine (2AP). The monomers may be used interchangeably with standard Fmoc
      PNA monomers. The DAP monomer was incorporated into a PNA and was found to
      selectively bind to T (DeltaT(m)>= +6  degrees C) in a complementary DNA strand.
      The 2AP monomer showed excellent discrimination of T (DeltaT(m)>= +12  degrees C)
      over the other nucleobases. 2AP also acted as a fluorescent probe of the PNA:DNA
      duplexes and displayed fluorescence quenching dependent on the opposite base.

PMID- 22159215
TI  - An efficient approach to dispacamide A and its derivatives.
AB  - Dispacamide A and new analogs of this marine alkaloid were prepared in seven
      steps with an overall yield ranging from 12 to 33%. The key step of the strategy
      was a stereocontrolled Knoevenagel condensation under microwave dielectric
      heating in the last step. In this condensation, the 2-aminoimidazolin-4-one
      hydrochloride partners 10a-c were synthesized in three steps with good overall
      yields (33-79%) via the ring closure of N-guanidino acetic acids 9a-c and the
      aldehydes 5a,b as the two others building-blocks, in 3 steps with 60-66% overall
      yields. The six synthetic products have been obtained with a Z geometry about
      their exocyclic bond on the basis of (13)C/(1)H long-range coupling constants
      using a gHSQMBC experiment.

PMID- 22159216
TI  - Reactions of green and black teas with Cu(II).
AB  - Electron paramagnetic resonance (EPR) measurements of the products of reactions
      between Cu(II) and samples of green and black teas showed spectral components
      from at least six different Cu(II) complexes with both tea types. Several of
      these complexes were common to both teas in spite of major differences in their
      polyphenol compositions. The pH range observed for complex formation, and the
      total signal intensity in the pH range 4-8, were greatly different from those for
      the reactions of Cu(II) with (-)-epigallocatechin gallate and gallic acid, the
      main polyphenols responsible for the free radical signals observed during
      oxidation of these beverages. Components with spectral parameters similar to
      those of Cu(II) complexes with theanine, the major amino acid in tea, may
      contribute to two of the spectra recorded under acidic conditions. However, the
      initial complexes formed at the lowest pH values investigated are still
      unidentified. EPR spectra with parameters consistent with Cu(II) polyphenol
      complexes were only observed under alkaline conditions, thus suggesting that
      components of tea other than polyphenols might be more important in reactions
      with copper, and possibly other transition metals, in solutions under
      physiological conditions.

PMID- 22159219
TI  - A dialog between glioma and microglia that promotes tumor invasiveness through
      the CCL2/CCR2/interleukin-6 axis.
AB  - Glioma cells in situ are surrounded by microglia, suggesting the potential of
      glioma-microglia interactions to produce various outcomes. As chemokines are
      important mediators of cell-cell communication, we sought first to identify
      commonly expressed chemokines in 16 human glioma lines. We found CCL2 (macrophage
      chemoattractant protein-1) messenger RNA to be expressed by the majority of
      glioma lines. However, these lines did not express the CCL2 receptor, CCR2, which
      was found on microglia. Next, we overexpressed CCL2 in the U87 glioma line, which
      has low basal level of CCL2, to investigate the hypothesis that glioma-secreted
      CCL2 interacts with microglia to affect glioma growth. Stable clones with 10- to
      12-fold elevation of CCL2 have similar growth rate and invasive capacity as
      vector controls when cultured in isolation. However, in coculture with microglia
      in a three-dimensional collagen gel matrix, the invasiveness of CCL2
      overexpressing clones was increased. Gene array analyses were then undertaken and
      they revealed that interleukin (IL)-6 was consistently increased in the
      coculture. Recombinant IL-6 enhanced the invasiveness of glioma cells when these
      were cultured alone, whereas a neutralizing antibody to IL-6 attenuated the
      microglia-stimulated glioma invasiveness. Finally, we found that human glioma
      specimens in situ contained IL-6 immunoreactivity that was expressed on CD68+
      cells. This study has uncovered a mechanism by which glioma cells exploit
      microglia for increased invasiveness. Specifically, glioma-derived CCL2 acts upon
      CCR2-bearing microglia, which then produces IL-6 to stimulate gliomas. The
      CCL2/CCR2/IL-6 loop is a potential therapeutic target for the currently incurable
      malignant gliomas.

PMID- 22159220
TI  - Decorin-mediated inhibition of colorectal cancer growth and migration is
      associated with E-cadherin in vitro and in mice.
AB  - Previous studies have shown that decorin expression is significantly reduced in
      colorectal cancer tissues and cancer cells, and genetic deletion of the decorin
      gene is sufficient to cause intestinal tumor formation in mice, resulting from a
      downregulation of p21, p27(kip1) and E-cadherin and an upregulation of beta
      catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes
      intestinal tumor formation through disruption of intestinal cell maturation.
      Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin
      and its implication in cancer formation and metastasis is largely unknown. Using
      a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of
      decorin in human colorectal cancer cells, we found that E-cadherin, a protein
      that regulates cell-cell adhesion, epithelial-mesenchymal transition and
      metastasis, was almost completely lost in Dcn(-/-) mouse intestine, and loss of
      decorin and E-cadherin accelerated colon cancer cell growth and invasion in Dcn(
      /-) mice. However, increasing decorin expression in colorectal cancer cells
      attenuated cancer cell malignancy, including inhibition of cancer cell
      proliferation, promotion of apoptosis and importantly, attenuation of cancer cell
      migration. All these changes were linked to the regulation of E-cadherin by
      decorin. Moreover, overexpression of decorin upregulated E-cadherin through
      increasing of E-cadherin protein stability as E-cadherin messenger RNA and
      promoter activity were not affected. Co-immunoprecipitation assay showed a
      physical binding between decorin and E-cadherin proteins. Taken together, our
      results provide direct evidence that decorin-mediated inhibition of colorectal
      cancer growth and migration are through the interaction with and stabilization of
      E-cadherin.

PMID- 22159221
TI  - Effect of dietary polyunsaturated fatty acids on castration-resistant Pten-null
      prostate cancer.
AB  - A common treatment of advanced prostate cancer involves the deprivation of
      androgens. Despite the initial response to hormonal therapy, eventually all the
      patients relapse. In the present study, we sought to determine whether dietary
      polyunsaturated fatty acid (PUFA) affects the development of castration-resistant
      prostate cancer. Cell culture, patient tissue microarray, allograft, xenograft,
      prostate-specific Pten knockout and omega-3 desaturase transgenic mouse models in
      conjunction with dietary manipulation, gene knockdown and knockout approaches
      were used to determine the effect of dietary PUFA on castration-resistant Pten
      null prostate cancer. We found that deletion of Pten increased androgen receptor
      (AR) expression and Pten-null prostate cells were castration resistant. Omega-3
      PUFA slowed down the growth of castration-resistant tumors as compared with omega
      6 PUFA. Omega-3 PUFA decreased AR protein to a similar extent in tumor cell
      cytosolic and nuclear fractions but had no effect on AR messenger RNA level.
      Omega-3 PUFA treatment appeared to accelerate AR protein degradation, which could
      be blocked by proteasome inhibitor MG132. Knockdown of AR significantly slowed
      down prostate cancer cell proliferation in the absence of androgens. Our data
      suggest that omega-3 PUFA inhibits castration-resistant prostate cancer in part
      by accelerating proteasome-dependent degradation of the AR protein. Dietary omega
      3 PUFA supplementation in conjunction with androgen ablation may significantly
      delay the development of castration-resistant prostate cancer in patients
      compared with androgen ablation alone.

PMID- 22159222
TI  - MicroRNA-34a suppresses malignant transformation by targeting c-Myc
      transcriptional complexes in human renal cell carcinoma.
AB  - We investigated the functional effects of microRNA-34a (miR-34a) on c-Myc
      transcriptional complexes in renal cell carcinoma. miR-34a down-regulated
      expression of multiple oncogenes including c-Myc by targeting its 3' untranslated
      region, which was revealed by luciferase reporter assays. miR-34a was also found
      to repress RhoA expression by suppressing the c-Myc-Skp2-Miz1 transcriptional
      complex that activates RhoA. Overexpression of c-Myc reversed miR-34a suppression
      of RhoA expression and inhibition of cell invasion, suggesting that miR-34a
      inhibits invasion by suppressing RhoA through c-Myc. miR-34a was also found to
      repress the c-Myc-P-TEFb transcription elongation complex, indicating one of the
      mechanisms by which miR-34a has profound effects on cellular functions. Our
      results demonstrate that miR-34a suppresses assembly and function of the c-Myc
      complex that activates or elongates transcription, indicating a novel role of miR
      34a in the regulation of transcription by c-Myc.

PMID- 22159223
TI  - Catechol-O-methyltransferase-mediated metabolism of 4-hydroxyestradiol inhibits
      the growth of human renal cancer cells through the apoptotic pathway.
AB  - Long-term exposure to estrogen and its metabolites may play an important role in
      renal cell carcinogenesis. Catechol-O-methyltransferase (COMT) participates in
      the estrogen metabolism pathway by neutralizing toxic substances. Although
      reduced COMT activity has been suggested to be a risk factor for estrogen
      associated cancers, no studies have investigated the biological significance of
      COMT in the pathogenesis of human renal cell cancers (RCCs). We initially found
      that COMT levels are significantly decreased in human RCC tissues and cells
      suggesting it plays a suppressive role in tumor development. However, transient
      overexpression of COMT has no functional effect on RCC cell lines. In contrast,
      when cells overexpressing COMT are treated with its substrate 4-hydroxyestradiol
      (4-OHE(2)), growth is inhibited by apoptotic cell death. We also found that COMT
      overexpression combined with 4-OHE(2) induces upregulation of growth arrest- and
      DNA damage-inducible protein alpha (GADD45alpha). We further show that
      downregulation of GADD45alpha by a small interfering RNA-mediated approach
      inhibits cell death, indicating the essential role of GADD45alpha in the
      underlying mechanism of COMT action in response to 4-OHE(2). Finally, 4
      methoxyestradiol fully reproduces the antiproliferative function of COMT with 4
      OHE(2) by promoting GADD45alpha induction. Together, these findings show that
      COMT in the presence of 4-OHE(2) prevents RCC cell proliferation by enhancing
      apoptosis and that GADD45alpha plays a critical role in the COMT-mediated
      inhibition of RCC.

PMID- 22159224
TI  - Aberrant cyclin A expression and centrosome overduplication induced by hepatitis
      B virus pre-S2 mutants and its implication in hepatocarcinogenesis.
AB  - Ground glass hepatocytes harboring hepatitis B virus (HBV) pre-S2 mutants have
      been recognized as pre-neoplastic lesions of hepatocellular carcinoma (HCC). The
      pre-S2 mutants accumulated in endoplasmic reticulum (ER) can induce ER stress,
      upregulate cyclin A and promote hepatocyte proliferation. Notably, cyclin A was
      aberrantly detected in the cytoplasm, instead of nucleus, of pre-S2 mutant
      transgenic mice livers, thereby raising the potential role of cytoplasmic cyclin
      A in HBV hepatocarcinogenesis. In this study, we confirmed that cyclin A was
      detected in the cytoplasm in the majority of HBV-related HCC tissues. In vitro,
      the pre-S2 mutant-initiated ER stress could induce cytoplasmic cyclin A mediated
      via cleavage by the calcium-dependent protease MU-calpain, resulting in an N
      terminal truncated product which was preferentially located in the cytoplasm. The
      aberrant cyclin A expression subsequently induced centrosome overduplication, and
      this effect was abolished by calpain-specific inhibitors or RNA interference
      targeting to cyclin A. Overall, our data indicate that HBV pre-S2 mutant may
      elicit aberrant cyclin A expression and centrosome overduplication through ER
      stress induction and thereby represent a potential mechanism for the chromosome
      instability in HBV hepatocarcinogenesis.

PMID- 22159225
TI  - Aurora B confers cancer cell resistance to TRAIL-induced apoptosis via
      phosphorylation of survivin.
AB  - Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis
      selectively in cancer cells while sparing normal cells. However, many cancer
      cells are resistant to TRAIL-induced cell death. In this study, we examined
      whether Aurora B, which is frequently overexpressed in cancer cells, is
      associated with TRAIL resistance. The protein levels of Aurora B were higher in
      TRAIL-resistant cancer cell lines than in TRAIL-sensitive cancer cell lines.
      Exogenously expressed Aurora B attenuated TRAIL-induced apoptosis in the tested
      TRAIL-sensitive cancer cell lines, whereas the small interfering RNA-mediated
      suppression of Aurora B expression stimulated TRAIL-mediated apoptosis in the
      tested TRAIL-resistant cancer cell lines. Furthermore, combined treatment with
      TRAIL and ZM447439, a specific inhibitor of Aurora B, synergistically induced
      apoptosis in various TRAIL-resistant cancer cells, suggesting that this combined
      regimen may represent an attractive strategy for effectively treating TRAIL
      resistant malignant cancers. Mechanistically, the inhibition of Aurora B activity
      in various cancer cells commonly downregulated survivin protein levels and
      potentiated the activation of caspase-3. In addition, Aurora B inhibition induced
      mitotic catastrophe, which also contributed to the sensitization of cells to
      TRAIL-mediated apoptosis. Interestingly, forced overexpression of Aurora B
      increased the protein levels of survivin, but not those of a non-phosphorylatable
      survivin mutant in which threonine 117 was replaced by alanine, indicating that
      phosphorylation of survivin is required for this effect. Furthermore, TRAIL
      induced apoptosis in MDA-MB-435S cells was attenuated by wild-type survivin but
      not by the non-phosphorylatable survivin mutant. Collectively, our results
      demonstrate that Aurora B confers TRAIL resistance to cancer cells via
      phosphorylation of survivin.

PMID- 22159226
TI  - Orphan receptor TR3 participates in cisplatin-induced apoptosis via Chk2
      phosphorylation to repress intestinal tumorigenesis.
AB  - Cisplatin is a widely used antitumor agent that induces aggressive cancer cell
      death via triggering cellular proteins involved in apoptosis. Here, we
      demonstrate that cisplatin effectively induces orphan nuclear receptor TR3
      phosphorylation by activating Chk2 kinase activity and promoting cross talk
      between these two proteins, thereby contributing to the repression of intestinal
      tumorigenesis via apoptosis. Mechanistic analysis has demonstrated that Chk2
      induced phosphorylation enables TR3 to bind to its response elements on the
      promoters of the BRE and RNF-7 genes, leading to the negative regulation of these
      two anti-apoptotic genes. Furthermore, the induction of apoptosis by cisplatin is
      mediated by TR3, and knockdown of TR3 reduces cisplatin-induced apoptosis in
      colon cancer cells by 27%. The role of TR3 in cisplatin chemotherapy is further
      clarified in mouse models. In Apc(min/+) mice, cisplatin inhibits intestinal
      tumorigenesis by 70% in a TR3 phosphorylation-dependent manner; however, the loss
      of TR3 function in Apc(min/+)/TR3(-/-) mice leads to the failure of cisplatin
      induced repression of tumorigenesis. Consistently, xenografts derived from TR3
      knockdown colon cancer cells are insensitive to cisplatin treatment, whereas a
      significant curative effect (50% inhibition) is observed in xenografts with
      functional TR3. Taken together, our study reveals a novel cross talk between Chk2
      and TR3 and sheds light on the mechanism of cisplatin-induced apoptosis through
      TR3. Therefore, TR3 may be a new target of cisplatin for colon cancer therapy.

PMID- 22159227
TI  - Activation of a Tip60/E2F1/ERCC1 network in human lung adenocarcinoma cells
      exposed to cisplatin.
AB  - The Tip60 and E2F1 proteins are key players of the cellular response induced by
      genotoxic stresses. Here, new insights into the involvement of both proteins
      during the DNA damage response are provided. We show that Tip60 interacts with
      E2F1 and promotes its acetylation. We identify the lysine residues 120/125 of the
      E2F1 protein as the prime target sites of Tip60 and show that acetylation at
      these sites promotes the accumulation of E2F1. Importantly, we demonstrate that
      cisplatin induces the accumulation of E2F1 in a Tip60-dependent manner. However,
      and in contrast to PCAF and p300, Tip60 is not required for the induction of
      apoptosis in cisplatin-treated cells. Instead, Tip60 and E2F1 are involved in the
      upregulation of the excision repair cross-complementation group 1 protein
      expression, an enzyme involved in the repair of cisplatin-induced DNA lesions.
      These findings identify Tip60 as a direct regulator of E2F1 and support their
      cooperative role in DNA repair.

PMID- 22159228
TI  - Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced
      colon cancer in mice.
AB  - Chronic inflammation is an underlying risk factor for colon cancer. Tumor
      necrosis factor alpha (TNF-alpha) plays a critical role in the development of
      inflammation-induced colon cancer in a mouse model. S-adenosylmethionine (SAMe)
      and its metabolite methylthioadenosine (MTA) can inhibit lipopolysaccharide
      induced TNF-alpha expression in macrophages. The aim of this work was to examine
      whether SAMe and MTA are effective in preventing inflammation-induced colon
      cancer and if so identify signaling pathways affected. Balb/c mice were treated
      with azoxymethane (AOM) and dextran sulfate sodium to induce colon cancer. Two
      days after AOM treatment, mice were divided into three groups: vehicle control,
      SAMe or MTA. Tumor load, histology, immunohistochemistry, gene and protein
      expression were determined. SAMe and MTA treatment reduced tumor load by ~40%.
      Both treatments raised SAMe and MTA levels but MTA also raised S
      adenosylhomocysteine levels. MTA treatment prevented the induction of many genes
      known to play pathogenetic roles in this model except for TNF-alpha and inducible
      nitric oxide synthase (iNOS). SAMe also had no effect on TNF-alpha or iNOS and
      was less inhibitory than MTA on the other genes. In vivo, both treatments induced
      apoptosis but inhibited proliferation, beta-catenin, nuclear factor kappa B
      activation and interleukin (IL) 6 signaling. Effect of SAMe and MTA on IL-6
      signaling was examined using Colo 205 colon cancer cells. In these cells, SAMe
      and MTA inhibited IL-6-induced IL-10 expression. MTA also inhibited IL-10
      transcription and signal transducer and activator of transcription 3 activation.
      In conclusion, SAMe and MTA reduced inflammation-induced colon cancer and
      inhibited several pathways important in colon carcinogenesis.

PMID- 22159229
TI  - alpha-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in
      prostate cancer and decreases xenograft tumor growth.
AB  - There is a need to characterize promising dietary agents for chemoprevention and
      therapy of prostate cancer (PCa). We examined the anticancer effect of alpha
      mangostin, derived from the mangosteen fruit, in human PCa cells and its role in
      targeting cell cycle-related proteins involved in prostate carcinogenesis. Using
      an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, we found
      that alpha-mangostin significantly decreases PCa cell viability in a dose
      dependent manner. Further analysis using flow cytometry identified cell cycle
      arrest along with apoptosis. To establish a more precise mechanism of action, we
      performed a cell free biochemical kinase assay against multiple cyclins/cyclin
      dependent kinases (CDKs) involved in cell cycle progression; the most significant
      inhibition in the cell free-based assays was CDK4, a critical component of the G1
      phase. Through molecular modeling, we evaluated alpha-mangostin against the
      adenosine triphosphate-binding pocket of CDK4 and propose three possible
      orientations that may result in CDK4 inhibition. We then performed an in vivo
      animal study to evaluate the ability of alpha-mangostin to suppress tumor growth.
      Athymic nude mice were implanted with 22Rv1 cells and treated with vehicle or
      alpha-mangostin (100 mg/kg) by oral gavage. At the conclusion of the study, mice
      in the control cohort had a tumor volume of 1190 mm(3), while the treatment group
      had a tumor volume of 410 mm(3) (P < 0.01). The ability of alpha-mangostin to
      inhibit PCa in vitro and in vivo suggests alpha-mangostin may be a novel agent
      for the management of PCa.

PMID- 22159230
TI  - Risk is not our business: safety of thoracic surgery in patients using
      antiplatelet therapy.
AB  - American Heart Association recommendations have changed preoperative management
      of patients with antiplatelet therapy (APT). We assessed safety and outcomes of
      surgery in patients who were receiving APT. A prospective study of patients
      operated on while receiving APT was matched with those with no APT (ratio 1:4),
      using the propensity score method. Logistic regression analysis was used to
      identify covariates among imbalanced baseline patient variables. Both chi(2) test
      and Fisher's test were used to calculate the probability value for the comparison
      of dichotomous variables. Between January 2008 and December 2010, 38 patients who
      received APT at the time of surgery were matched with 141 patients who had not
      received APT. APT indications were a history of myocardial infarction, coronary
      artery by-pass graft and/or valve replacement (19), coronary artery stent (11)
      and severe peripheral vascular disease (8). None of the patients required re
      operation for bleeding. Two patients received blood transfusions. The amount of
      chest tube drainage was not statistically significantly different. There were no
      statistically significant differences between the outcomes for the operative
      time, length of hospital stay, estimated blood loss or morbidity. The results
      show that thoracic surgical procedures can safely be performed in patients
      receiving APT at the time of surgery, with no increased risk of bleeding or
      morbidity and no differences in the operative time and the length of hospital
      stay.

PMID- 22159231
TI  - Endovascular aortic repair of patent ductus arteriosus in an adult patient.
AB  - We describe the case of a large patent ductus arteriosus in a 52-year old man,
      which was deemed unsuitable for coil occlusion or Amplatzer duct occluder. His
      ductus was successfully closed using Talent prostheses (Medtronic AVE, Santa
      Rosa, CA, USA). The postoperative course was uneventful.

PMID- 22159232
TI  - What are the differences in outcomes between right-sided active infective
      endocarditis with and without left-sided infection?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: in patients with isolated right-sided
      infective endocarditis (RSE) is the outcome of surgical management the same as in
      patients with or without left-sided involvement? Altogether, 419 papers were
      found using the reported search, six of which represented the best evidence to
      answer the clinical question. Two studies point towards better outcomes with
      isolated RSE. In one paper, mortality was significantly lower in isolated RSE
      patients (P = 0.0093) for the duration of the follow-up time (median 488 patient
      years). Two studies reported early mortality (<30 days) for RSE patients at 3.6
      and 3.8%, respectively. Combined right- and left-sided endocarditis (RLSE)
      patients were found to have a poorer pre-operative clinical presentation than
      isolated RSE patients with a greater requirement for inotropic support (P <
      0.006) and the likelihood of an emergency operation (P < 0.001). They had a
      poorer intra-operative course with a higher incidence of cardiac abscess
      formation (P < 0.001). One study suggested that there is no significant
      difference in in-hospital and long-term mortality between intravenous drug abuse
      (IVDA) patients and non-IVDA patients. Left-heart involvement in the IVDA group
      was 61.5%. This was in-line with the published literature, demonstrating a rise
      in RLSE in IVDA compared with non-IVDA patients. Three articles looking at
      isolated left-sided endocarditis (LSE) gave mortality rates in the surgical group
      to be 27.1, 27.8 and 38%, respectively. In one study, the LSE mortality was not
      different for native vs. prosthetic valve infection (OR 0.65, 95% CI 0.23-1.87).
      After propensity matching and adjusting for hazards, the complication rate in the
      LSE group was higher and this translated to a higher mortality rate. We conclude
      from the literature that outcomes are more favourable with lower early and late
      mortality for isolated RSE patients over pure LSE or combined RLSE.

PMID- 22159233
TI  - Ruptured aneurysm of replaced left hepatic artery as a cause of haemorrhagic
      shock: a challenge of diagnosis and treatment.
AB  - An isolated, spontaneous, ruptured aneurysm of the replaced left hepatic artery
      (LHA) arising from the left gastric artery, in a 72-year-old female, leading to
      haemorrhagic shock treated by surgical ligation is reported. To our best
      knowledge, this is the second case report of a ruptured hepatic artery aneurysm
      in this location. A thorough knowledge of hepatic arterial anatomy and
      variations, and prompt diagnosis and urgent surgical intervention are necessary
      in such a potentially lethal condition.

PMID- 22159234
TI  - Multiple synchronous primary tumours in a single lobe.
AB  - We present the case of a 70-year-old man with three synchronous histologically
      different primary tumours in the same lobe. He initially presented with an
      intermittent productive cough, dyspnoea and non-specific abdominal pains.
      Radiological investigation revealed three areas of high-intensity fludeoxyglucose
      uptake of varying size within the right upper lobe. He underwent thoracoscopic
      right upper lobectomy. Histological analysis confirmed the three lesions to be
      undifferentiated squamous cell carcinoma, adenocarcinoma and atypical adenomatous
      hyperplasia. The reclassification of the T descriptors of the tumour-node
      metastasis staging of a lung cancer has lead to the transition of classification
      of tumour nodules in the ipsilateral primary tumour lobe from T4 to T3. In the
      case of our patient, this has lead to the downstaging of the tumour allowing
      consideration for surgical management.

PMID- 22159235
TI  - Folding mitral valvuloplasty without posterior leaflet resection for calcified
      mitral annulus.
AB  - Mitral valve annular calcification has long been a challenge in repairing
      posterior mitral valve prolapse. Folding valvuloplasty of the posterior leaflet
      without resection provides a means of circumventing common procedural
      complications. This report demonstrates the success of folding valvuloplasty
      without resection in the treatment of mitral valve prolapse and severe annular
      calcification.

PMID- 22159236
TI  - Post-operative acute exacerbation of pulmonary fibrosis in lung cancer patients
      undergoing lung resection.
AB  - Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) in lung cancer
      patients is a critical factor in post-operative mortality. The cause of AE
      development is unknown and AE may occur in patients without the diagnosis of IPF.
      We have conducted a retrospective study of consecutive patients who underwent
      lung cancer surgery since January 2004. Sixty-two patients with fibrous findings
      in preoperative high-resolution computed tomography were enrolled in the present
      study and clinicopathological factors were analysed. AE was observed in 6 of 62
      patients. The frequency of AE according to the type of fibrous changes
      classification was 1/7 in the usual interstitial pneumonia (UIP) pattern, 1/16 in
      the cellular non-specific interstitial pneumonia (NSIP) pattern, 4/25 in the
      fibrotic NSIP pattern and 0/14 in the unclassified or focal fibrous changes
      pattern. Preoperative Krebs von den Lungen-6 (KL-6) was higher in patients with
      AE than in those without AE. In patients who underwent partial resection, AE did
      not develop even with high KL-6 levels. In conclusion, in patients with both the
      UIP and the NSIP patterns, AE development is possible. In patients with a high
      risk of AE, such as those with high KL-6 values, limited surgery may be an option
      to prevent AE development.

PMID- 22159237
TI  - Extracorporeal membrane oxygenation support for abdominal aortic aneurysms
      surgery in high-risk patients.
AB  - Surgical treatment of an abdominal aortic aneurysm in patients with a heart
      disease is risky. Aortic cross-clamping is featured by important consequences on
      cardiac, renal and gastrointestinal functions. Endovascular aortic repair is
      considered to be the gold standard in patients with severe comorbidities.
      However, in the case of unsuccessful endovascular treatment, surgery can be
      reconsidered with the use of extracorporeal membrane oxygenation, which seems to
      be a new tool for the management of cardiac and gastrointestinal events ensuring
      better post-operative outcomes.

PMID- 22159238
TI  - Can early aortic root surgery prevent further aortic dissection in Marfan
      syndrome?
AB  - We reviewed 50 patients with Marfan syndrome who underwent surgery for aortic
      root pathologies comprising a root aneurysm without (n = 25; group A) and with (n
      = 25; group B) dissection. Aortic root repair included Bentall (n = 37) and valve
      sparing (n = 13) procedures. Hospital mortality was 4.0%. Twenty-two patients
      required 36 repeat surgeries on the distal aorta. The main indication for re
      intervention was the dilation of the false lumen. In group A, the distal aorta
      was stable for up to 7 years, but new dissection developed in 5 (33.3%) of the 15
      patients who were followed up for >7 years after the root repair. Actuarial
      survival including operative mortality was 88.1 and 65.0% at 10 and 20 years,
      respectively; groups A and B did not significantly differ. Rates of freedom from
      all-cause death, new dissection or repeated aortic surgery were 60.1, 44.5 and
      26.0% at 5, 10 and 15 years, respectively. Group A was significantly better than
      group B. Prophylactic aortic root repair apparently reduces the likelihood of
      overall adverse events, but it cannot guarantee the prevention of further aortic
      dissection. A multidisciplinary approach is needed for patients with Marfan
      syndrome.

PMID- 22159239
TI  - Surgical treatment of stage IV non-small cell lung cancer.
AB  - Most stage IV non-small-cell lung cancer (NSCLC) patients are not amenable to
      curative treatment. The purpose of this study was to analyse our initial
      experience with an aggressive surgical strategy for stage IV NSCLC, and to define
      which patients can benefit from this treatment. Forty-six stage IV NSCLC patients
      who underwent surgical resection of both primary lung cancer and metastatic sites
      from April 1989 to December 2010 were included in this study. The record of each
      patient was reviewed for age, gender, pN status, sites of metastasis, histology,
      surgical procedure and duration of survival. There were 13 females and 33 males.
      Their median age was 62.0 years (range, 44-82 years). The overall 5-year survival
      rate was 23.3% (median, 20.0 months), and the disease-free survival rate was
      15.8% at 5 years (median, 16.1 months). Patients with the pN2 status had a
      significantly worse survival than patients with a pN0 or pN1 status (8.6 versus
      33.1%, P = 0.0497). According to a multivariate Cox proportional hazards
      analysis, no independent predictor of survival was identified. The results of our
      study suggest that surgical treatment can extend the survival in stage IV NSCLC
      patients if the patients can tolerate surgery.

PMID- 22159240
TI  - Fluorine-18-fluorodeoxyglucose uptake in a benign oesophageal leiomyoma: a
      potential pitfall in diagnosis.
AB  - Positron-emission tomography scans (PET) with fluorine-18-fluorodeoxyglucose
      ((18)F- FDG) are usually negative in leiomyomas. Two patients underwent a PET
      that showed an increased (18)F- FDG uptake of the distal oesophagus suggestive
      for malignancy. Both patients were operated on and histologic examination
      revealed a benign leiomyoma in both cases. We conclude that oesophageal
      leiomyomas are a potential cause of a false-positive PET. A high level of caution
      is needed in these diagnostically challenging cases to prevent unnecessary
      surgical procedures.

PMID- 22159241
TI  - Transapical aortic valve replacement through a chronic apical aneurysm.
AB  - Transapical aortic valve replacement through an apical aneurysm is traditionally
      contraindicated because of the risk of severe systemic embolization when thrombi
      are present. However, a chronic fibrotic aneurysm without apical thrombi carries
      a low risk of distal embolization and can be safely employed for a transapical
      transcatheter aortic valve replacement in case of absence of an alternative
      access site (severe vascular disease, small vascular sizes and diseased calcified
      aorta). We illustrate our experience with a 73-year-old patient suffering from
      symptomatic aortic valve stenosis, coronary artery disease with occluded left
      anterior descending artery, left ventricular apical aneurysm and severe
      peripheral vascular disease, who successfully underwent a transapical 26 mm
      SapienTM XT stent-valve implantation through the fibrotic thin akinetic apical
      wall.

PMID- 22159242
TI  - Alveolar adenoma: an extremely rare innocent coin lesion.
AB  - Alveolar adenoma is an extremely rare benign tumour of the lung. Less than 30
      cases have been reported in the English literature. A 42-year-old asymptomatic
      female who presented with a solitary peripheral pulmonary nodule on chest
      roentgenogram underwent thoracoscopic wedge resection and was diagnosed with this
      rare tumour. The indolent clinical progression and the absence of recurrence and
      metastasis after complete resection are the most important characteristics of
      this tumour. The classical solitary pulmonary nodule is a common and vexing
      problem. Nodules are extremely common in clinical practice and challenging to
      manage. Solitary pulmonary nodules can represent different specific lung
      diseases, focal non-specific inflammations, and primary and secondary malignant
      tumours. Identification of malignant nodules is important because they represent
      a potentially curable form of lung cancer.

PMID- 22159243
TI  - Behcet's disease with aneurysm of internal iliac artery and percutaneous
      treatment.
AB  - Behcet's disease (BD), described in 1937 by Hulusi Behcet, is a multisystemic
      inflammatory disorder. In this paper, we report a large pseudoaneurysm of the
      internal iliac artery in a patient who had BD, and was admitted to emergency
      service complaining of leg pain and the percutaneous treatment of the pathology
      which followed.

PMID- 22159244
TI  - Acute lower limb ischaemia due to delayed upstream migration of an iliac stent.
AB  - We report a case of acute limb ischaemia due to unusual upstream stent migration
      into the aorta 2 years after successful kissing stenting. Angiography showed a
      misplacement of both common iliac stent into the aorta, upstream migration with a
      fracture on the left external iliac stent into the iliac common artery, occlusion
      of the left iliac and femoral artery, dilatation of aortic bifurcation and stent
      separation on the right side. The patient underwent a successful axillo-bifemoral
      bypass graft. Vessel wall remodelling due to overestimation of stent size, aortic
      turbulence and rebound effect may explain this complication.

PMID- 22159245
TI  - Biology of colorectal pulmonary metastasis: implications for surgical resection.
AB  - In colorectal cancer, little high grade evidence for cure, life extension,
      disease modification or palliation achieved by pulmonary metastasectomy exists.
      This has prompted the pulmonary metastasectomy in colorectal cancer (PulMiCC)
      trial. Reappraisal of the biological facts on colorectal metastasis may, however,
      shed light on an alternative avenue of clinical management. Early onset of
      metastasis, short doubling time and a short disease-free interval are all
      associated with poor clinical outcomes. Selecting who will be cured (i.e. no
      occult metastasis) remains the holy grail for pulmonary metastasectomy surgery.
      Serial CT scans can be utilized to calculate the tumour doubling time by
      volumetric analysis. Knowing the doubling time and size of the largest
      metastasis, which by definition is the first cell that has successfully spread
      from the primary site, the time of initial metastasis can be predicted. More
      importantly, using the doubling time, calculating the time interval from the
      primary surgery to the point at which all pulmonary metastases are visible should
      be possible. Perhaps watchful waiting, with interval CT scanning, followed by
      pulmonary metastasectomy should be utilized, rather than clinical opinion or
      randomization in a trial based upon first presentation.

PMID- 22159246
TI  - Does video-assisted mediastinoscopy have a better lymph node yield and safety
      profile than conventional mediastinoscopy?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was whether video-assisted mediastinoscopy (VAM) has a better
      lymph node yield and safety profile than the conventional mediastinoscopy (CM). A
      total of 194 papers were found, using the reported searches, of which five
      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. Two studies to date
      have directly compared CM and VAM with respect to lymph node yield, calculated
      diagnostics performance and complication rate. In both of these, lymph node yield
      is shown to be higher using VAM with better sensitivity, negative predictive
      value and accuracy rates. The favourable figures of lymph node sampling are found
      to be statistically significant in the single study providing such analysis.
      Complication rates using VAM are low, however, in the one instance where it is
      reported as higher than CM, the extensive lymph node dissection used in this
      technique may be a reasonable explanation for this finding. All studies described
      here exemplify VAM as a safe and useful tool in mediastinal staging, lymph node
      dissection and tissue diagnosis of mediastinal diseases given its superior
      visualization of surrounding structures and advantage of bimanual dissection. The
      future scope for diagnostic and therapeutic indications of cervical
      mediastinscopy is anticipated with recent advances and new techniques, such as
      video-assisted mediastinoscopic lymphadenectomy and virtual mediastinscopy.

PMID- 22159247
TI  - What is the optimum antibiotic prophylaxis in patients undergoing implantation of
      a left ventricular assist device?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was what the optimum antibiotic prophylaxis in patients
      undergoing implantation of a left ventricular assist device (LVAD) is. A total of
      373 papers were found, of which 11 represented the best evidence. The authors,
      date, journal, study type, population, main outcome measures and results are
      tabulated. Eight retrospective and two prospective studies, including one
      randomized controlled trial (RCT), were identified. Although highly variable, the
      prophylactic antibiotic protocols employed in these studies generally favour the
      use of vancomycin, a cephalosporin, beta-lactam and quinolone, with the option of
      additional fluconazole and mupirocin. However, the lack of standardized
      definitions for infection, and variations in the choice, timing and duration of
      prophylactic antibiotics complicates the interpretation of reported infection
      rates. Driveline and pocket infections comprised the majority of infectious
      complications, and were principally attributed to Gram-positive organisms, such
      as Staphylococcus, as well as Pseudomonas species. We conclude that a beta-lactam
      be used for primary prophylaxis, with vancomycin where the risk of MRSA is high.
      Topical mupirocin and an anti-fungal are also recommended. Prophylaxis should
      commence prior to device insertion, and be continued into the peri- and post
      operative period. Large-scale RCTs are necessary to assess the impact of
      different antibiotic regimens on infection within LVAD recipients.

PMID- 22159248
TI  - A simple method for occlusion of both venae cavae in total cardiopulmonary bypass
      for robotic surgery.
AB  - We describe a novel surgical technique for occlusion of the superior and inferior
      venae cavae which allows opening of the right atrium safely during robotic
      cardiac surgery.

PMID- 22159249
TI  - Intrathoracic gossypiboma causing intractable cough.
AB  - A 45-year old woman presented with a 5-month history of coughing, eight months
      after surgery for post-tubercular fibrosis with bronchiectasis. Upon computerized
      tomography (CT) scanning, a sponge-like structure was seen in the pneumonectomy
      cavity near the stump of the right main bronchus. Bronchoscopic examination
      revealed a whitish mass blocking the right main bronchial stump which, upon
      attempted retrieval, yielded long threads of cotton fibres from a retained
      surgical gauze. The gossypiboma was removed surgically and the patient became
      symptom-free. Although rare after thoracic surgery, gossypibomas need to be
      considered in symptoms following surgery.

PMID- 22159250
TI  - The effect of season of operation on the survival of patients with resected non
      small cell lung cancer.
AB  - Stage has been defined as the major prognostic factor in resected non-small cell
      lung cancer (NSCLC). However, there is some evidence that indicates season of
      operation could play a role in the survival of patients. Between January 1995 and
      June 2008, 698 (621 men and 77 women) patients who had undergone pulmonary
      resection for NSCLC were evaluated. Patients were analysed according to surgical
      pathological stages and month of the year in which they were operated. Vitamin D
      receptor (VDR) polymorphism was also analysed in 62 patients. The median survival
      time in all patients was 60 +/- 6 months (95% confidence interval (CI): 44-81
      months). The survival of patients who underwent resection in winter was
      statistically significantly shorter than those operated in summer (P = 0.03).
      When patients were analysed according to T, N and season, resection time of the
      year was calculated to be an independent determinant of survival (P = 0.04). A
      VDR genotype was also associated with better prognosis (P = 0.04). Season of the
      operation, VDR polymorphism and N status seemed to have independent effects on
      survival of operated NSCLC patients.

PMID- 22159251
TI  - Syphilitic aneurysm of the ascending aorta.
AB  - Syphilitic aortic aneurysm is a rare occurrence in the antibiotic era, making the
      diagnose assumption even more infrequent. Nonetheless, this pathology can appear
      and should be suspected in patients with aortic aneurysm. We report a case of a
      57-year old patient who presents with neurosyphilis and, in the following study,
      a large ascending aorta aneurysm is identified. The authors discuss the
      diagnostic challenge, the epidemiologic concerns, surgical indication and
      treatment and subsequent follow-up.

PMID- 22159252
TI  - Human CD34+ stem cells promote healing of diabetic foot ulcers in rats.
AB  - OBJECTIVE: Diabetic patients with foot ulcers usually manifest with high
      amputation and mortality rates. Preliminary evidence supports the effectiveness
      of stem cell (St) therapy on diabetic foot ulcers. The objective of this study
      was to evaluate the efficacy of stem cells in the healing of wounds among
      streptozotocin-induced diabetic albino rats. METHODS: Thirty male albino rats
      were divided into three groups each of 10 rats: control group, diabetic control
      (DC) group and St group. Diabetes was induced by intra-peritoneal injection of
      streptozotocin. A full thickness circular wound of ~10 mm in diameter was
      performed on the front of right legs of all rats. In the diabetic St group, the
      wounds were treated by injection of umbilical cord blood-derived CD34+ stem cells
      into the wound bed. Half of each group rats were sacrificed after 1 week and the
      rest after 2 weeks. The wound areas were used for histopathology,
      immunohistochemistry and transmission electron microscope studies. Assessment of
      wound surface area, epidermal thickness, blood vessel proliferation and collagen
      deposition were performed. RESULTS: There was a significant decrease in mean
      wound surface area, increase in mean epidermal thickness, blood vessel
      proliferation and collagen deposition in the St group compared with the DC group.
      CONCLUSION: Treatment with CD34+-enriched cells decreased wound size, accelerated
      epidermal healing and dramatically accelerated revascularization of the wounds
      compared with the DC group.

PMID- 22159253
TI  - Impact of off-pump to on-pump conversion rate on post-operative results in
      patients undergoing off-pump coronary artery bypass.
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: In patients undergoing off-pump coronary
      artery bypass (OPCAB) surgery, does the off-pump to on-pump conversion rate have
      an impact on post-operative results? Altogether more than 420 papers were found
      using the reported search, of which 14 randomized controlled trials (RCTs)
      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 and ordered according
      to the sample size. In the 14 RCTs reviewed, the off-pump to on-pump conversion
      rate incidence ranged from 0 to 13.3%. The most frequent causes of conversion
      were haemodynamic instability and intramyocardial-coronary target. A low
      conversion rate (<2%) was reported by five studies. Three of them did not show
      any difference in terms of mortality between the OPCAB and on-pump groups, one
      showed better survival of the OPCAB group at 5 years, and one reported better
      early survival of the OPCAB group. Three of these trials describe a high OPCAB
      experience and reported that patients undergoing OPCAB had a shorter post
      operative stay and lower morbidity compared with patients undergoing on-pump
      coronary artery bypass grafting. Five RCTs showed a high conversion rate (>9%),
      and among them, one reported lower morbidity of the OPCAB patients, three were
      not able to show any benefit in terms of morbidity of the OPCAB, and one reported
      worse survival and patency graft rate of the OPCAB group. Four RCTs reported
      conversion rates ranging from 3.7 to 7.0%, describing a wide spectrum of results.
      We conclude that RCTs with a high off-pump to on-pump conversion rate were often
      associated with a lower experience in OPCAB of the surgeons participating in the
      trials. These studies were also mostly unable to show any benefit in terms of
      mortality or morbidity of OPCAB over the on-pump strategy. On the contrary, a low
      conversion rate is mostly reported by RCTs with a high structured experience in
      OPCAB. These trials were mostly able to show a benefit, in terms of morbidity and
      survival, of the OPCAB over the on-pump strategy.

PMID- 22159254
TI  - Early bioprosthetic valve failure caused by preserved native mitral valve
      leaflets.
AB  - The importance of preservation of subvalvular apparatus and valve-ventricular
      continuity during mitral valve replacement (MVR) has been suggested for many
      years. The chordal-sparing MVR has been shown to be superior to the standard MVR
      with chordal resection in terms of improved left ventricular function and has
      been considered to be a safe procedure. However, we encounter a rare case
      requiring early reoperation for bioprosthetic valve failure caused by preserved
      leaflets after chordal-sparing MVR.

PMID- 22159255
TI  - Pulmonary metastasectomy: a multivariate analysis of 440 patients undergoing
      complete resection.
AB  - Surgical resection is currently a standard approach for isolated lung metastases
      from different primary tumours. The aim of the present analysis is to evaluate
      the outcome of patients submitted to complete resection of pulmonary metastases
      and to determine prognostic factors for long-term survival. A group of 440
      consecutive patients previously diagnosed with primary malignant solid tumours
      and submitted to complete surgical resection of lung nodules with suspected or
      diagnosed metastatic lesion were retrospectively reviewed. The average follow-up
      time was 43.2 months (range: 0-192) and the 60-month O.S. was 43.7%. Univariate
      analysis: patients with adenocarcinoma presented the highest 5-year survival
      rates (53.4%, P = 0.0001); DFI >36 months (P < 0.0001), number of nodules on CT
      scan (P = 0.0052), number of malignant nodules resected (P = 0.0252) and the size
      of the largest resected nodule (P < 0.0001) were also significant. Multivariate
      analysis: number of malignant nodules resected (P = 0.01), size of the largest
      nodule resected (P = 0.001), DFI >36 months (P < 0.001) and histology of the
      primary tumour (P = 0.017) had significant impact on survival. The benefit of
      such an aggressive surgical approach is only limited to selected subgroups of
      patients. The decision to consider a patient for resection of metastastic disease
      should include factors beyond the feasibility of complete removal.

PMID- 22159256
TI  - Washout after lobectomy: is water more effective than normal saline in preventing
      local recurrence?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was: 'is water washout more effective than
      normal saline washout after lobectomy in preventing local recurrence?' Altogether
      more than 48 papers were found using the reported search, of which nine
      represented the best evidence to answer the clinical question. The authors,
      journal, date, country of publication, patient group studied, study type,
      relevant outcomes and results of these papers are tabulated. Tumour cell
      'spillage' after cancer resection is linked to a worse prognosis, so washout to
      minimize contamination is an established surgical technique. While the mechanical
      effects of lavage are well validated, the differential cytocidal effects of water
      versus saline as irrigation fluids are not. There are currently no studies
      addressing this issue in the thoracic surgery setting, after lung cancer
      lobectomy. However, the majority of relevant papers describe the use of basic in
      vitro methods and animal models to produce data that can conceivably be
      extrapolated to the clinical question in hand. The number of studies is small,
      and some have technical limitations. While two of the better-designed experiments
      suggest that water exerts a superior cytocidal effect on tumour cells, data from
      other studies are somewhat unimpressive, with two studies reporting that water
      washout controls tumour growth to a lesser extent than saline. This, together
      with the complete paucity of clinical trials on the subject, leads us to conclude
      that water is unlikely to represent a superior irrigation fluid in lung cancer
      patients after lobectomy.

PMID- 22159257
TI  - Does the use of extended criteria donors influence early and long-term results of
      lung transplantation?
AB  - A best evidence topic was constructed according to a structured protocol. The
      question addressed was whether the presence of extended criteria donors
      influences the early and long-term results in patients referred for lung
      transplantation. Of the 30 papers found using a report search, 14 presented the
      best evidence to answer the clinical question. The authors, journal, date,
      country of publication, study type, group studied, relevant outcomes and results
      of these papers are given. In total, we recorded 10 retrospective studies that
      considered all the donor criteria for comparing marginal donors (MDs) and
      standard donors. On the one hand, six of them showed no difference between the
      two groups in terms of early and long-term results. On the other hand, four
      studies demonstrated a negative impact of MDs on various early outcomes
      (mortality, primary graft dysfunction, duration of mechanical ventilation, length
      of stay in intensive care unit), whereas no significant negative influence on
      survival has ever been described when screening MD results. More precisely, when
      analysing the role of individual factors of marginality, as done in two of the 14
      studies, a significant negative impact was observed for a low level of PaO(2) at
      the time of harvesting, positive bronchoscopy and smoking history. More
      specifically, the first two criteria have been validated by several authors, both
      in multicentre and cohort studies. Finally, the importance of avoiding the
      donation of the lung from an MD to a high-risk recipient emerged, whereas the
      association with single or bilateral transplants remains more controversial.
      Hence, current evidence suggests that there are no contraindications-given the
      absence of negative impact on survival-for the use of MDs for the transplant of a
      proposed standard receiver. However, given the low level of evidence of published
      studies, caution is necessary in order to avoid organ shortage, despite these
      encouraging results.

PMID- 22159258
TI  - Impact of incomplete surgical revascularization on survival.
AB  - Complete revascularization is considered superior to incomplete revascularization
      (IR), with better long-term survival and a lower rate of reintervention. However,
      it has yet to be established whether this difference is due directly to IR as a
      surgical strategy or whether this approach is merely a marker of more severe
      coronary disease and more rapid progression. We believe that IR is a prognostic
      marker for a more complex coronary pathology, and adverse effects are probably
      due to the preoperative condition of the patient. In fact, although IR may
      negatively affect long-term outcomes, it may be, when wisely chosen, the ideal
      treatment strategy in selected high-risk patients. IR can derive from a surgical
      strategy of target vessel revascularization, where the impact of surgery is
      minimized to reduce perioperative mortality and morbidity, aiming to achieve the
      best feasible safe revascularization.

PMID- 22159259
TI  - Does adding ketamine to morphine patient-controlled analgesia safely improve post
      thoracotomy pain?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was 'is the addition of ketamine to morphine
      patient-controlled analgesia (PCA) following thoracic surgery superior to
      morphine alone'. Altogether 201 papers were found using the reported search, of
      which nine 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. This consisted
      of one systematic review of PCA morphine with ketamine (PCA-MK) trials, one meta
      analysis of PCA-MK trials, four randomized controlled trials of PCA-MK, one meta
      analysis of trials using a variety of peri-operative ketamine regimes and two
      cohort studies of PCA-MK. Main outcomes measured included pain score rated on
      visual analogue scale, morphine consumption and incidence of psychotomimetic side
      effects/hallucination. Two papers reported the measurements of respiratory
      function. This evidence shows that adding ketamine to morphine PCA is safe, with
      a reported incidence of hallucination requiring intervention of 2.9%, and a meta
      analysis finding an incidence of all central nervous system side effects of 18%
      compared with 15% with morphine alone, P = 0.31, RR 1.27 with 95% CI (0.8-2.01).
      All randomized controlled trials of its use following thoracic surgery found no
      hallucination or psychological side effect. All five studies in thoracic surgery
      (n = 243) found reduced morphine requirements with PCA-MK. Pain scores were
      significantly lower in PCA-MK patients in thoracic surgery papers, with one paper
      additionally reporting increased patient satisfaction. However, no significant
      improvement was found in a meta-analysis of five papers studying PCA-MK in a
      variety of surgical settings. Both papers reporting respiratory outcomes found
      improved oxygen saturations and PaCO(2) levels in PCA-MK patients following
      thoracic surgery. We conclude that adding low-dose ketamine to morphine PCA is
      safe and post-thoracotomy may provide better pain control than PCA with morphine
      alone (PCA-MO), with reduced morphine consumption and possible improvement in
      respiratory function. These studies thus support the routine use of PCA-MK
      instead of PCA-MO to improve post-thoracotomy pain control.

PMID- 22159260
TI  - Calibrated cusp sizers to facilitate aortic valve repair: development and
      clinical application.
AB  - Based on the natural mathematical relationships between the components of the
      human tri-leaflet aortic valve, new calibrated cusp sizers were developed in
      order to facilitate aortic valve assessment in the operating room and enhance the
      chance for a perfect restoration of aortic valve competence. These sizers were
      used clinically to guide the implementation of established aortic valve repair
      techniques in 10 consecutive patients with severe aortic valve regurgitation.
      Valve repair was successful in all cases, and at a median follow-up was 5.5
      months, aortic valve function remained stable, with aortic regurgitation <=1+ in
      every patient and no significant gradient across the aortic valves. This
      preliminary clinical experience indicates that the calibrated cusp sizers can
      provide reliable insight into the mechanism of aortic valve insufficiency, and
      can guide aortic valve repair techniques successfully. We hope that the
      simplicity and reproducibility of this method would assist in its dissemination
      and further increase the percentage of aortic valves that are repaired when
      compared with current practice.

PMID- 22159261
TI  - Diagnostic enigma: primary pulmonary artery sarcoma.
AB  - Primary angiosarcoma of pulmonary artery is a very rare lesion. We present a case
      of primary angiosarcoma that was initially misdiagnosed as a subacute massive
      pulmonary thromboembolism in a 30-year-old man. This rare disease is usually
      indistinguishable from acute or chronic thromboembolic disease of the pulmonary
      arteries. The clinical and radiological findings of pulmonary artery angiosarcoma
      are similar to those of pulmonary thromboembolism. Although the incidence of
      pulmonary artery angiosarcoma is very low, our case demonstrates that this
      disease entity should be included in the differential diagnosis of pulmonary
      thromboembolism. Patients with early identification can have curative potential
      with aggressive surgical intervention.

PMID- 22159262
TI  - Long-term self-management of anticoagulation therapy after mechanical heart valve
      replacement in outside trial conditions.
AB  - In this investigation, we hypothesize that quality of oral anticoagulation (OA)
      and long-term outcome after mechanical heart valve (MHV) replacement with self
      management (Self-M) of OA is superior to conventional anticoagulation treatment
      (Conv-T), even in outside trial conditions. One hundred sixty patients (78.8%
      aortic valve replacements) were trained in international normalized ratio Self-M
      and 260 patients (86.2% aortic valve replacements) preferred Conv-T. Mean follow
      up was 8.6 +/- 2.1 years, representing 3612 patient-years. During follow-up,
      37.2% bleedings and 10.6% thromboembolic events were recorded in the Self-M group
      versus 39.6% bleedings (P = 0.213) and 15.4% thromboembolic events (P = 0.064) in
      the Conv-T group. Serious adverse events were significantly lower in the Self-M
      group [grade III bleeding events causing disability or death: 0 versus 4.6% (P =
      0.03); grade III thromboembolic events: 0.6 versus 5.0% (P = 0.011)]. Patients
      with Self-M were significantly more satisfied with their OA management and their
      quality of life (P < 0.001). Actuarial survival after 1, 5 and 10 years was 100,
      99 and 97 with Self-M and 100, 95 and 81% with Conv-T, respectively (P < 0.001).
      Univariate risk factors for mortality were age (P = 0.008), type of operation (P
      = 0.021) and conventional OA (P < 0.001). In multivariate analysis, only
      conventional OA reached significance (P < 0.001). We conclude that in a routine
      setting under outside trial conditions Self-M of OA improves long-term outcome
      and treatment quality.

PMID- 22159263
TI  - Patients' satisfaction and wound-site complications after radial artery
      harvesting for coronary artery bypass.
AB  - The aim of the study was to establish patients' satisfaction and the incidence of
      wound-site complications after radial artery (RA) harvesting for bypass surgery.
      A telephonic quality of life questionnaire was performed in 306 consecutive
      patients who had undergone coronary artery bypass grafting with the use of RA
      with the open technique. A psychometric Likert scale was used to define the
      degree of patients' satisfaction. The questionnaire concerned arm pain, cosmesis
      and mobility, sensory and neurological complications, and patients' general
      health state. The median values and the modal scores achieved the maximal value
      of satisfaction for all site-related complications and the mean scores were >4
      out of 5. The median patients' general health state was 4. Cosmetic result of the
      wound was considered at least acceptable by 98% of patients. The incidence of
      impairing peripheral neurological complications was 16.7%. The degree of
      patients' satisfaction after RA harvesting was more than satisfactory and the
      incidence of wound-site complications was acceptable. The incidence of
      neurological injuries was lower than previously described.

PMID- 22159264
TI  - Does getting smokers to stop smoking before lung resections reduce their risk?
AB  - A best-evidence topic in thoracic surgery was written according to a structured
      protocol. The question of whether the incidence of major pulmonary morbidity
      after lung resection was associated with the timing of smoking cessation was
      addressed. Overall 49 papers were found using the reported search outlined below,
      of which 7 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. In most
      studies, smoking abstinence was shown to reduce the incidence of post-operative
      pulmonary complications (PPCs) such as pneumonia, respiratory distress,
      atelectasis, air leakage, bronchopleural fistula and re-intubation. The timing of
      cessation is not clearly identified, although there is some evidence showing
      reduction in risk of PPCs with increasing interval since cessation. Two studies
      suggested that smoking abstinence for at least 4 weeks prior to surgery was
      necessary in order to reduce the incidence of major pulmonary events.
      Furthermore, it was also shown that a pre-operative smoke-free period of >10
      weeks produced complication rates similar to those of patients who had never
      smoked. We conclude that smoking cessation reduces the risk of PPCs. All patients
      should be advised and counseled to stop smoking before any form of lung
      resection.

PMID- 22159265
TI  - Cor triatriatum dexter: unusual features in utero and after birth.
AB  - Cor triatriatum dexter is a rare congenital anomaly, caused by the persistence of
      the right valve of the sinus venosus, which divides the right atrium into two
      chambers and its diagnosis is rather difficult, due to the features often
      mimicking Ebstein's anomaly. We describe a case followed from the foetal age for
      a relative right ventricular hypoplasia and suspicious pulmonary stenosis and
      diagnosed after birth to have cor triatriatum dexter with an obstructing membrane
      in the right atrium, needing surgical correction, done successfully.

PMID- 22159267
TI  - Individually addressable electrode array for multianalyte electrochemiluminescent
      immunoassay based on a sequential triggering strategy.
AB  - Multianalyte immunoassay in a single run is often necessary to monitor or
      quantitate several components in a complex sample matrix for various purposes. In
      this paper we present a novel, individually addressable electrode array for
      sequential electrochemiluminescent (ECL) immunoassay using a non-array detector.
      An immunosensor array was fabricated by site-selectively immobilizing multiple
      antigens on different electrodes. With a competitive immunoassay format, the
      amounts of the bound Ru(bpy)(3)(2+) derivative labeled antibodies decreased with
      the increase of the antigens in the sample, and the ECL signals from different
      immunosensors were collected in turn by a photomultiplier with the aid of a home
      made single-pore-three-throw switch. Using human IgG and rat IgG as model
      analytes, this multianalyte immunoassay showed detection limits down to 8.9 and
      7.2 ng mL(-1) for them, respectively. The results for real sample analysis
      demonstrated that this strategy can provide a simple, sensitive, low-cost and
      high-throughput ECL immunosensor array for clinical diagnosis.

PMID- 22159266
TI  - Non-invasive cerebral oxygenation reflects mixed venous oxygen saturation during
      the varying haemodynamic conditions in patients undergoing transapical
      transcatheter aortic valve implantation.
AB  - Transapical transcatheter aortic valve implantation (TA-TAVI) is increasingly
      used to treat aortic valve stenosis in high-risk patients. Mixed venous oxygen
      saturation (SvO(2)) is still the 'gold standard' for the determination of the
      systemic oxygen delivery to consumption ratio in cardiac surgery patients. Recent
      data suggest that regional cerebral oxygen saturation (rScO(2)) determined by
      near-infrared spectroscopy is closely related to SvO(2). The present study
      compares rScO(2) and SvO(2) in patients undergoing TA-TAVI. n = 20 cardiac
      surgery patients scheduled for TA-TAVI were enrolled in this prospective
      observational study. SvO(2) and rScO(2) were determined at predefined time points
      during the procedure. Correlation and Bland-Altman analysis of the complete data
      set showed a correlation coefficient of r(2 )= 0.7 between rScO(2) and SvO(2) (P
      < 0.0001), a mean difference (bias) of 5.8 with limits of agreement (1.96 SD) of 
      6.8 to 18.3% and a percentage error of 17.5%. At all predefined time points
      correlation was moderate (r(2 )= 0.50) to close (r = 0.84), and the percentage
      error was <24%. RScO(2) determined by near-infrared spectroscopy is correlated to
      SvO(2) during varying haemodynamic conditions in patients undergoing TA-TAVI.
      This suggests that rScO(2) is reflective not only of the cerebral, but also of
      the systemic oxygen balance.

PMID- 22159268
TI  - Direct preparation of thiazoles, imidazoles, imidazopyridines and thiazolidines
      from alkenes.
AB  - A range of heterocycles, namely thiazoles, imidazoles, imidazopyridines,
      thiazolidines and dimethoxyindoles, have been synthesised directly from alkenes
      via a two-step ketoidoination/cyclisation protocol. The alkene starting materials
      are themselves readily accessible using many different and well-established
      approaches, and allow access to a variety of heterocycles with excellent yields
      and regioselectivity.

PMID- 22159270
TI  - A sensitive and selective DNAzyme-based flow cytometric method for detecting Pb2+
      ions.
AB  - A sensitive and selective Pb(2+) sensor based on GR-5 DNAzyme has been developed
      by a flow cytometric method.

PMID- 22159271
TI  - Pi-Bond maximization of graphene in hydrogen addition reactions.
AB  - Thermodynamic stability of graphene hydrides increases in an approximately linear
      way with the numbers of pi-bonds they contain. Thus, pi-bond maximization is the
      primary driving force for hydrogen addition reactions of graphene. The previously
      reported thermal preference of sp(2)/sp(3)-phase separation of graphene hydrides
      is a straightforward effect of pi-bond maximization. Although not well applicable
      to hydroxylation and epoxidation, the pi-bond maximization principle also holds
      approximately for the fluorination reactions of graphene. The findings can be
      used to help locate the lowest-energy structures for graphene hydrides and to
      estimate the hydrogenation energy without first-principles calculations.

PMID- 22159272
TI  - Anatase TiO2 nanocrystals with exposed {001} facets on graphene sheets via
      molecular grafting for enhanced photocatalytic activity.
AB  - Owing to their extensive practical applications and fundamental importance, the
      controllable synthesis of well-faceted anatase TiO(2) crystal with high
      percentage of reactive facets has attracted increasing attention. Here, nano
      sized anatase TiO(2) sheets mainly dominated by {001} facets had been prepared on
      graphene sheets by using a facile solvothermal synthetic route. The percentage of
      {001} facets in TiO(2) nanosheets was calculated to be ca. 64%. The morphologies,
      structural properties, growth procedures and photocatalytic activities of the
      resultant TiO(2)/graphene nanocomposites were investigated. In comparison with
      commercial P25 and pure TiO(2) nanosheets, the composite exhibited significant
      improvement in photocatalytic degradation of the azo dye Rhodamine B under
      visible light irradiation. The enhancement of photocatalytic activity and
      stability was attributed to the effective charge anti-recombination of graphene
      and the high catalytic activity of {001} facets.

PMID- 22159273
TI  - Fructose containing sugars modulate mRNA of lipogenic genes ACC and FAS and
      protein levels of transcription factors ChREBP and SREBP1c with no effect on body
      weight or liver fat.
AB  - The aim of this study was to determine the effects of high-glucose, high-fructose
      and high-sucrose diets on weight gain, liver lipid metabolism and gene expression
      of proteins involved with hepatic fat metabolism. Rats were fed a diet containing
      either 60% glucose, 60% fructose, 60% sucrose, or a standard chow for 28 days.
      Results indicated that high-fructose and high-sucrose diets were associated with
      higher mRNA levels of gene transcripts involved with fat synthesis; ACC, FAS and
      ChREBP, with no change in SREBP-1C mRNA. The protein level of ChREBP and SREBP1c
      was similar in liver homogenates from all groups, but were higher in nuclear
      fractions from the liver of high-fructose and high-sucrose fed rats. The mRNA
      level of gene transcripts involved with fat oxidation was the same in all three
      diets, whilst a high-fructose diet was associated with greater amount of mRNA of
      the fat transporter CD36. Despite the changes in mRNA of lipogenic proteins, the
      body weight of animals from each group was the same and the livers from rats fed
      high-fructose and high-sucrose diets did not contain more fat than control diet
      livers. In conclusion, changing the composition of the principal monosaccharide
      in the diet to a fructose containing sugar elicits changes in the level of
      hepatic mRNA of lipogenic and fat transport proteins and protein levels of their
      transcriptional regulators; however this is not associated with any changes in
      body weight or liver fat content.

PMID- 22159276
TI  - Light-activatable molecular beacons with a caged loop sequence.
AB  - We have synthesized molecular beacons with caged nucleobases in the loop region.
      These constructs remain non-fluorescent in the presence of their target RNA but
      can be fully activated by light (366 or 405 nm) in vitro and in HEK293 cells. We
      suggest that this technology will be useful for single molecule RNA tracking in
      living cells.

PMID- 22159277
TI  - LPA stimulates intestinal DRA gene transcription via LPA2 receptor, PI3K/AKT, and
      c-Fos-dependent pathway.
AB  - DRA (downregulated in adenoma) or SLC26A3 is the major apical anion exchanger
      mediating Cl(-) absorption in intestinal epithelial cells. Disturbances in DRA
      function and expression have been implicated in diarrheal conditions such as
      congenital chloride diarrhea and inflammatory bowel diseases. Previous studies
      have shown that DRA is subject to regulation by short-term and transcriptional
      mechanisms. In this regard, we have recently shown that short-term treatment by
      lysophosphatidic acid (LPA), an important bioactive phospholipid, stimulates Cl(
      )/HCO(3)(-)(OH(-)) exchange activity via an increase in DRA surface levels in
      human intestinal epithelial cells. However, the long-term effects of LPA on DRA
      at the level of gene transcription have not been examined. The present studies
      were aimed at investigating the effects of LPA on DRA function and expression as
      well as elucidating the mechanisms underlying its transcriptional regulation.
      Long-term LPA treatment increased the Cl(-)/HCO(3)(-) exchange activity in Caco-2
      cells. LPA treatment (50-100 MUM) of Caco-2 cells significantly stimulated DRA
      mRNA levels and DRA promoter activity (-1183/+114). This increase in DRA promoter
      activity involved the LPA2 receptor and phosphatidylinositol 3-kinase (PI3K)/AKT
      pathways. Progressive deletions from -1183/+114 to -790/+114 abrogated the
      stimulatory effects of LPA, indicating that the -1183/-790 promoter region
      harbors LPA response elements. Utilizing EMSA and mutational studies, our results
      showed that LPA induced the DRA promoter activity in a c-Fos-dependent manner.
      LPA also increased the protein expression of c-Fos and c-Jun in Caco-2 cells.
      Furthermore, overexpression of c-Fos but not c-Jun enhanced the DRA promoter
      activity. This increase in DRA transcription in response to LPA indicates that
      LPA may act as an antidiarrheal agent and could be exploited for the treatment of
      diarrhea associated with inflammatory or infectious diseases of the gut.

PMID- 22159278
TI  - Suppression of acute hepatic injury by a synthetic prostacyclin agonist through
      hepatocyte growth factor expression.
AB  - Previous studies have demonstrated that mice disrupted with the cyclooxygenase-2
      gene showed much more severe liver damage compared with wild-type mice after
      liver injury, and prostaglandins (PGs) such as PGE(1/2) and PGI(2) have decreased
      hepatic injury, but the mechanisms by which prostaglandins exhibit protective
      action on the liver have yet to be addressed. In the present study, we
      investigated the mechanism of the protective action of PGI(2) using the synthetic
      IP receptor agonist ONO-1301. In primary cultures of hepatocytes and
      nonparenchymal liver cells, ONO-1301 did not show protective action directly on
      hepatocytes, whereas it stimulated expression of hepatocyte growth factor (HGF)
      in nonparenchymal liver cells. In mice, peroral administration of ONO-1301
      increased hepatic gene expression and protein levels of HGF. Injections of CCl4
      induced acute liver injury in mice, but the onset of acute liver injury was
      strongly suppressed by administration of ONO-1301. The increases in serum alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) by CCl4 were
      suppressed by 10 mg/kg ONO-1301 to 39.4 and 33.6%, respectively. When
      neutralizing antibody against HGF was administered with ONO-1301 and CCl4, the
      decreases by ONO-1301 in serum ALT and AST, apoptotic liver cells, and expansion
      of necrotic areas in liver tissue were strongly reversed by neutralization of
      endogenous HGF. These results indicate that ONO-1301 increases expression of HGF
      and that hepatoprotective action of ONO-1301 in CCl4-induced liver injury may be
      attributable to its activity to induce expression of HGF, at least in part. The
      potential for involvement of HGF-Met-mediated signaling in the hepatotrophic
      action of endogenous prostaglandins generated by injury-dependent cyclooxygenase
      2 induction is considerable.

PMID- 22159279
TI  - An ex vivo method for studying mucus formation, properties, and thickness in
      human colonic biopsies and mouse small and large intestinal explants.
AB  - The colon mucus layers minimize the contact between the luminal flora and the
      epithelial cells, and defects in this barrier may lead to colonic inflammation.
      We now describe an ex vivo method for analysis of mucus properties in human colon
      and mouse small and large intestine. Intestinal explants were mounted in
      horizontal perfusion chambers. The mucus surface was visualized by adding
      charcoal particles on the apical side, and mucus thickness was measured using a
      micropipette. Mucus thickness, adhesion, and growth rate were recorded for 1 h.
      In mouse and human colon, the ability of the mucus to act as a barrier to beads
      the size of bacteria was also evaluated. Tissue viability was monitored by
      transepithelial potential difference. In mouse ileum, the mucus could be removed
      by gentle aspiration, whereas in colon ~40 MUm of the mucus remained attached to
      the epithelial surface. Both mouse and human colon had an inner mucus layer that
      was not penetrated by the fluorescent beads. Spontaneous mucus growth was
      observed in human (240 MUm/h) and mouse (100 MUm/h) colon but not in mouse ileum.
      In contrast, stimulation with carbachol induced a higher mucus secretion in ileum
      than colon (mouse ileum: Delta200 MUm, mouse colon: Delta130 MUm, human colon:
      Delta140 MUm). In conclusion, while retaining key properties from the mucus
      system in vivo, this setup also allows for studies of the highly dynamic mucus
      system under well-controlled conditions.

PMID- 22159280
TI  - EP2 and EP4 receptors on muscularis resident macrophages mediate LPS-induced
      intestinal dysmotility via iNOS upregulation through cAMP/ERK signals.
AB  - Intestinal resident macrophages play an important role in gastrointestinal
      dysmotility by producing prostaglandins (PGs) and nitric oxide (NO) in
      inflammatory conditions. The causal correlation between PGs and NO in
      gastrointestinal inflammation has not been elucidated. In this study, we examined
      the possible role of PGE(2) in the LPS-inducible inducible NO synthase (iNOS)
      gene expression in murine distal ileal tissue and macrophages. Treatment of ileal
      tissue with LPS increased the iNOS and cyclooxygenase (COX)-2 gene expression,
      which lead to intestinal dysmotility. However, LPS did not induce the expression
      of iNOS and COX-2 in tissue from macrophage colony-stimulating factor-deficient
      op/op mice, indicating that these genes are expressed in intestinal resident
      macrophages. iNOS and COX-2 protein were also expressed in dextran-phagocytized
      macrophages in the muscle layer. CAY10404, a COX-2 inhibitor, diminished LPS
      dependent iNOS gene upregulation in wild-type mouse ileal tissue and also in
      RAW264.7 macrophages, indicating that PGs upregulate iNOS gene expression. EP(2)
      and EP(4) agonists upregulated iNOS gene expression in ileal tissue and isolated
      resident macrophages. iNOS mRNA induction mediated by LPS was decreased in the
      ileum isolated from EP(2) or EP(4) knockout mice. In addition, LPS failed to
      decrease the motility of EP(2) and EP(4) knockout mice ileum. EP(2)- or EP(4)
      mediated iNOS expression was attenuated by KT-5720, a PKA inhibitor and PD-98059,
      an ERK inhibitor. Forskolin or dibutyryl-cAMP mimics upregulation of iNOS gene
      expression in macrophages. In conclusion, COX-2-derived PGE(2) induces iNOS
      expression through cAMP/ERK pathways by activating EP(2) and EP(4) receptors in
      muscularis macrophages. NO produced in muscularis macrophages induces dysmotility
      during gastrointestinal inflammation.

PMID- 22159281
TI  - Galectin-3 modulates phagocytosis-induced stellate cell activation and liver
      fibrosis in vivo.
AB  - Hepatic stellate cells (HSC), the key fibrogenic cells of the liver,
      transdifferentiate into myofibroblasts upon phagocytosis of apoptotic
      hepatocytes. Galectin-3, a beta-galactoside-binding lectin, is a regulator of the
      phagocytic process. In this study, our aim was to study the mechanism by which
      extracellular galectin-3 modulates HSC phagocytosis and activation. The role of
      galectin-3 in engulfment was evaluated by phagocytosis and integrin binding
      assays in primary HSC. Galectin-3 expression was studied by real-time PCR and
      enzyme-linked immunosorbent assay, and in vivo studies were done in wild-type and
      galectin-3(-/-) mice. We found that HSC from galectin-3(-/-) mice displayed
      decreased phagocytic activity, expression of transforming growth factor-beta1,
      and procollagen alpha1(I). Recombinant galectin-3 reversed this defect,
      suggesting that extracellular galectin-3 is required for HSC activation. Galectin
      3 facilitated the alpha(v)beta(3) heterodimer-dependent binding, indicating that
      galectin-3 modulates HSC phagocytosis via cross-linking this integrin and
      enhancing the tethering of apoptotic cells. Blocking integrin alpha(v)beta(3)
      resulted in decreased phagocytosis. Galectin-3 expression and release were
      induced in active HSC engulfing apoptotic cells, and this was mediated by the
      nuclear factor-kappaB signaling. The upregulation of galectin-3 in active HSC was
      further confirmed in vivo in bile duct-ligated (BDL) rats. Galectin-3(-/-) mice
      displayed significantly decreased fibrosis, with reduced expression of alpha
      smooth muscle actin and procollagen alpha1(I) following BDL. In summary,
      extracellular galectin-3 plays a key role in liver fibrosis by mediating HSC
      phagocytosis, activation, and subsequent autocrine and paracrine signaling by a
      feedforward mechanism.

PMID- 22159283
TI  - Oxygen molecule dissociation on carbon nanostructures with different types of
      nitrogen doping.
AB  - The energy barrier of oxygen molecule dissociation on carbon nanotubes or
      graphene with different types of nitrogen doping is investigated using density
      functional theory. The results show that the energy barriers can be reduced
      efficiently by all types of nitrogen doping in both carbon nanotubes and
      graphene. Graphite-like nitrogen and Stone-Wales defect nitrogen decrease the
      energy barrier more efficiently than pyridine-like nitrogen, and a dissociation
      barrier lower than 0.2 eV can be obtained. Higher nitrogen concentration reduces
      the energy barrier much more efficiently for graphite-like nitrogen. These
      observations are closely related to partial occupation of pi* orbitals and change
      of work functions. Our results thus provide useful insights into the oxygen
      reduction reactions.

PMID- 22159282
TI  - Functionalization of multi-walled carbon nanotubes with coumarin derivatives and
      their biological evaluation.
AB  - We report the synthesis and the characterization of different multi-walled carbon
      nanotubes (MWCNTs) linked to natural molecules, 5,7-coumarins and/or oleic acid,
      obtained from purified pristine MWCNTs by a cascade of chemical
      functionalization. The activities of these modified MWCNTs were investigated in
      vitro on human umbilical vein endothelial cells (HUVECs) by evaluating their
      ability to influence cell viability and to induce cell apoptosis. Our data showed
      that pristine MWCNTs are markedly cytotoxic; conversely, the carboxylated carbon
      nanotubes, much more readily dispersed in aqueous solutions and CNT-Link, the key
      intermediate designed by us for the drug anchorage, are biocompatible at the
      tested concentrations (1 and 10 MUg ml(-1)).

PMID- 22159284
TI  - A rapid and facile method for measuring corrosion rates using dynamic light
      scattering.
AB  - A dynamic light scattering (DLS) method was adopted for measuring the corrosion
      of iron nanoparticles. The average diameter of the nanoparticles in a sodium
      chloride suspension increased linearly with time as iron oxide layers formed
      around the nanoparticles. The nanoparticle corrosion rate determined by DLS was
      found to be almost identical to the value obtained by conventional immersion
      tests (ASTM G31). The DLS method offers the advantage that measurements may be
      completed within several hours under natural corrosion conditions whereas the
      conventional immersion method requires several months. Application of the DLS
      method to alloy nanoparticles with a variety of chromium compositions showed that
      the nanoparticle sizes changed nonlinearly over time, and the curves were best
      fit by a first order exponential function. The first order time constants were
      found to be linearly related to the corrosion rates determined by ASTM G31.

PMID- 22159286
TI  - Novel hexagonal {V=O}6-containing sandwich-type cluster accompanied by in situ
      carbon-carbon bond formation of organic cations.
AB  - Two novel sandwich-type polyanions containing hexagonal {V=O}(6) group
      (H(2)tpy)(Hbpe)(3)H[(VO)(6)(SbW(9)O(33))(2)].2H(2)O (1) and
      (H(2)tcy)(6)(Hbpp)(6)H(4)[VW(12)O(40)][(VO)(6)(SbW(9)O(33))(2)](3).30H(2)O (2)
      (tpy = 4-(2,3,4-tri(pyridin-4-yl)butyl)pyridine, bpe = 1,2-(4-pyridyl)ethene, tcy
      = 1,2,4,5-tetra(pyridin-4-yl)cyclohexanol, bpp = 1,3-bis-(4-pyridyl)propane),
      were reported. Both compounds are built upon the complex hydrogen bonding
      networks of C-H...O and N-H...O occurred among inorganic anions and organic
      cations. Unusual in situ organic reactions involving C-C coupling are also
      observed in 1 and 2 regardless of the rigid bpe or flexible bpp. Compound 2
      represents a rare case in which nano-sized alpha-Keggin [VW(12)O(40)](4-) and
      sandwich-type [(VO)(6)(SbW(9)O(33))(2)](6-) anionic clusters are present in a
      common crystal framework.

PMID- 22159287
TI  - A methodology for preparing nanostructured biomolecular interfaces with high
      enzymatic activity.
AB  - The development of a novel method for functionalizing nanopatterned surfaces with
      catalytically active proteins is reported. This method involves using dip-pen
      nanolithography (DPN) and polymer pen lithography (PPL) to generate nanoscale
      patterns of coenzyme A, followed by a phosphopantetheinyl transferase-mediated
      coupling between coenzyme A and proteins fused to the ybbR-tag. By exploiting the
      ability to generate protein features over large areas afforded by DPN and PPL, it
      was now possible to measure protein activity directly on these surfaces. It was
      found that proteins immobilized on the nanoscale features not only display higher
      activity per area with decreasing feature size, but are also robust and can be
      used for repeated catalytic cycles. The immobilization method is applicable to a
      variety of proteins and gives rise to superior activity compared to proteins
      attached in random orientations on the surface.

PMID- 22159289
TI  - Impact of phloretin and phloridzin on the formation of Maillard reaction products
      in aqueous models composed of glucose and L-lysine or its derivatives.
AB  - In the present study, the effects of phloretin and phloridzin on the formation of
      Maillard reaction products in a lysine-glucose model with different reactant
      ratios were systematically investigated. In terms of the formation of Maillard
      type volatiles, phloretin and phloridzin treatmen could significantly reduce
      their generation, where the effects depend on the ratio of lysine to glucose used
      in the model systems. Phloretin and phloridzin could also affect the colour
      development of Maillard reactions; especially phloretin, which could
      significantly promote the formation of brown products in the system with the
      lowest ratio of lysine to glucose. Based on the carbon module labelling (CAMOLA)
      technique and HPLC-DAD-ESI/MS analysis, it was found that phloretin and
      phloridzin could actively participate in the Maillard reaction and directly react
      with different reactive carbonyl species. The effect of phloretin and phloridzin
      treatment in both N(alpha)-acetyllysine-glucose (AC-glu), and N-acetyl-gly-lys
      methyl ester acetate salt-glucose (AG-glu) model systems, which are close to the
      Maillard reactions occurring in real food, where the free amino groups of lysine
      residues were considered as the reactive site, were further investigated. Similar
      impacts on the formation of Maillard-type volatiles and brown products as in the
      lysine-glucose models were observed which can also be explained by the capability
      of phloretin and phloridzin to quench sugar fragments formed in these model
      reactions.

PMID- 22159290
TI  - One pot biosynthesis of gold NPs using red cabbage extracts.
AB  - Red cabbage extract was used as reducing agent and capping agent for the
      synthesis of gold NPs. The method developed is environmentally friendly and
      allows the control of NPs shape and size by changing the pH value and the
      concentration of aqueous red cabbage extract solution.

PMID- 22159292
TI  - Synthesis and reactivity of a bis-sultone cross-linker for peptide conjugation
      and [18F]-radiolabelling via unusual "double click" approach.
AB  - A novel homobifunctional cross-linker based on a bis-sultone benzenic scaffold
      was synthesised. The potential utility of this bioconjugation reagent was
      demonstrated through the preparation of an original prosthetic group suitable for
      the [(18)F]-labelling of peptides. The labelling strategy is based on the
      nucleophilic fluorination via the ring-opening of a first sultone moiety followed
      by the nucleophilic ring-opening of the second remanent sultone by a reactive
      amine of the biopolymer. Beyond the one-step radiolabelling of the peptide, the
      second main advantage of this strategy is the release of free sulfonic acid
      moieties making the separation of the targeted [(18)F]-tagged sulfonated compound
      from its non-sulfonated precursor easier and thus faster. This first report of
      the successful use of a bis-sultone moiety as a versatile bioconjugatable group
      was demonstrated through a comprehensive reactivity study involving various
      nucleophiles, especially those commonly found in biopolymers. An illustrative
      example, highlighting the potential of this unusual and promising "double click"
      conjugation approach, was devoted to the radiolabelling of a biological relevant
      peptide.

PMID- 22159293
TI  - Random dsDNA-templated formation of copper nanoparticles as novel fluorescence
      probes for label-free lead ions detection.
AB  - A simple label-free method for the detection of Pb(2+) ions with high selectivity
      and sensitivity has been developed by using random double-strand DNA-templated
      formation of copper nanoparticles as novel fluorescence probes in aqueous
      solution.

PMID- 22159294
TI  - Molecular wire of urea in carbon nanotube: a molecular dynamics study.
AB  - We perform molecular dynamics simulations of narrow single-walled carbon
      nanotubes (SWNTs) in aqueous urea to investigate the structure and dynamical
      behavior of urea molecules inside the SWNT. Even at low urea concentrations
      (e.g., 0.5 M), we have observed spontaneous and continuous filling of SWNT with a
      one-dimensional urea wire (leaving very few water molecules inside the SWNT). The
      urea wire is structurally ordered, both translationally and orientationally, with
      a contiguous hydrogen-bonded network and concerted urea's dipole orientations.
      Interestingly, despite the symmetric nature of the whole system, the potential
      energy profile of urea along the SWNT is asymmetric, arising from the ordering of
      asymmetric urea partial charge distribution (or dipole moment) in confined
      environment. Furthermore, we study the kinetics of confined urea and find that
      the permeation of urea molecules through the SWNT decreases significantly (by a
      factor of ~20) compared to that of water molecules, due to the stronger
      dispersion interaction of urea with SWNT than water, and a maximum in urea
      permeation happens around a concentration of 5 M. These findings might shed some
      light on the better understanding of unique properties of molecular wires
      (particularly the wires formed by polar organic small molecules) confined within
      both artificial and biological nanochannels, and are expected to have practical
      applications such as the electronic devices for signal transduction and
      multiplication at the nanoscale.

PMID- 22159295
TI  - The first facile stereoselectivity switch in the polymerization of rac-lactide-
      from heteroselective to isoselective dialkylgallium alkoxides with the help of N
      heterocyclic carbenes.
AB  - The reaction of N-heterocyclic carbene (NHC) with dimeric dialkylgallium
      alkoxides, acting as nonselective or heteroselective catalysts in the
      polymerization of rac-LA, leads to highly active and isoselective monomeric
      Me(2)Ga(NHC)OR catalysts, resulting for the first time in the facile switch of
      stereoselectivity.

PMID- 22159296
TI  - Unusual coordination mode of tetradentate Schiff base cobalt(III) complexes.
AB  - Contrary to the stereotype, Jacobsen's catalyst, chiral (salcy)Co(III)OAc adopts
      an unusual binding mode. The tetradentate {ONNO} ligand does not form a square
      plane but wraps cobalt in a cis-beta fashion while acetate is chelating.

PMID- 22159297
TI  - Lentil polyphenol extract prevents angiotensin II-induced hypertension, vascular
      remodelling and perivascular fibrosis.
AB  - The objective of the study was to investigate whether chronic administration of
      the Morton lentil polyphenol extract (MLPE), which possesses rich phenolic
      compounds and a high antioxidant activity, had any protective effects on
      angiotensin II-induced hypertension. After four weeks of subcutaneous infusion of
      angiotensin II (200 ng kg(-1) min(-1)) in male SD rats, the water intake and mean
      artery pressure was significantly increased by 39.8% and 48.3%, respectively, as
      compared with the control. The media/lumen ratio of the small arteries in the
      heart and kidneys were increased by 117% and 168% by angiotensin II infusion. The
      perivascular fibrosis was increased by 65% and 32% in the heart and kidneys,
      respectively. Levels of the reactive oxygen species in the aorta was enhanced by
      115.8%. In another group of rats, which received four weeks of lentil extract
      administration (1% freeze-dried MLPE in the drinking water), followed by another
      four weeks of extract administration plus angiotensin II infusion, the
      angiotensin II-induced enhancement in water intake and mean artery pressures
      decreased by 12.7% and 8.2%, respectively, as compared with the rats that
      received angiotensin II infusion alone. The angiotensin II-induced rats showed
      increases in the media/lumen ratios which were attenuated by 43.6% and 47.2% in
      the small arteries of heart and kidneys, respectively. Angiotensin II-induced
      perivascular fibrosis was attenuated by 30% and 26% in the rats that received the
      extract. Angiotensin II-induced rats showed reactive oxygen species levels in the
      aorta was reduced by 48.9%. These findings demonstrated that lentil extract
      attenuated angiotensin II-induced hypertension and associated pathological
      changes, including remodelling and perivascular fibrosis in the small resistant
      arteries of heart and kidneys.

PMID- 22159298
TI  - Synthesis and characterization of self-assembled nanofiber-bundles of V2O5: their
      electrochemical and field emission properties.
AB  - High-quality self-assembled V(2)O(5) nanofiber-bundles (NBs) are synthesized by a
      simple and direct hydrothermal method using a vanadium(v) hydroxylamido complex
      as a vanadium source in the presence of HNO(3). The possible reaction pathway for
      the formation of V(2)O(5) NBs is discussed and demonstrated that HNO(3) functions
      both as an oxidizing and as an acidification agent. V(2)O(5) NBs are single
      crystals of an orthorhombic phase that have grown along the [010] direction. A
      bundle is made of indefinite numbers of homogeneous V(2)O(5) nanofibers where
      nanofibers have lengths up to several micrometres and widths ranging between 20
      and 50 nm. As-prepared V(2)O(5) NBs display a high electrochemical performance in
      a non-aqueous electrolyte as a cathode material for lithium ion batteries. Field
      emission properties are also investigated which shows that a low turn-on field of
      ~1.84 V MUm(-1) is required to draw the emission current density of 10 MUA cm(
      2).

PMID- 22159299
TI  - Insights on the binding ability of a new adenine analog: 7-amine-1,2,4
      triazolo[1,5-a]pyrimidine. Synthesis and magnetic study of the first copper(II)
      complexes.
AB  - Conventional reactions of the new multidentate ligand 7-amine-1,2,4-triazolo[1,5
      a]pyrimidine (7atp, 1) with copper(II) salts lead to four novel multidimensional
      coordination complexes [Cu(7atp)(mal)(H(2)O)(2)].H(2)O (2), [Cu(2)(MU
      7atp)(4)(H(2)O)(2)](ClO(4))(4).3H(2)O (3), {[Cu(7atp)(2)(MU-ox)].3H(2)O}(n) (4)
      and {[Cu(7atp)(2)(MU-suc)].2H(2)O}(n) (5), where ox(2-), mal(2-) and suc(2-) mean
      oxalate, malonate and succinate, respectively. In these compounds, the 7atp
      ligand coordinates monodentately through its atom N3, except for compound 3,
      which displays N3-N4 coordination mode, giving rise to all to structures with
      diverse topologies and dimensionality. Compound 2 is a mononuclear entity, 3
      consists of dinuclear species, 4 is a zig-zag chain with oxalate as a bridging
      ligand and 5 is a succinate-bridged mono-dimensional system. All polynuclear
      metal complexes show antiferromagnetic interactions of with J values ranging from
      -0.12 to -49.5 cm(-1). The ligand donor capabilities have been estimated by
      topological analyses of the electron density (QTAIM) and electron localization
      function (ELF), obtained by DFT calculations. The compounds are the first
      structurally characterized copper(II) complexes containing the 7atp ligand.

PMID- 22159300
TI  - Transition metal-catalysed (4 + 3) cycloaddition reactions involving allyl
      cations.
AB  - In this emerging area article, we focus on novel intramolecular transition metal
      catalysed (4 + 3)-cycloaddition reactions of allenedienes in which the allene
      acts as an allylic-cation surrogate. This process has emerged as a powerful tool
      for the construction not only of complex seven-membered rings containing
      compounds but also different types of useful molecular skeletons by the proper
      selection of the catalyst. The transformation proceeds with high chemo- and
      stereoselectivity mainly because it occurs through an exo-like concerted
      transition state which exhibits a clear in-plane aromatic character. Despite
      that, different reaction mechanisms (i.e. stepwise processes) are also possible
      depending on the nucleophilicity of the diene moiety.

PMID- 22159301
TI  - The impact of systematic dietary counseling during the first year of life on
      prevalence rates of anemia and iron deficiency at 12-16 months.
AB  - OBJECTIVE: To evaluate the impact that a program based on maternal dietary
      counseling covering breastfeeding and healthy complementary feeding had on the
      prevalence of iron deficiency, anemia and iron deficiency anemia in children aged
      12 to 16 months. METHODS: Newborn infants were randomized at birth to an
      intervention or a control group. Mothers in the intervention group received home
      visits during the children's first year of life on a monthly basis up to 6
      months, and at 8, 10 and 12 months. The mothers in the control group received
      visits for data collection when children reached 6 and 12 months. All children
      were visited at ages between 12 and 16 months and 24-hour dietary recalls and
      hemoglobin and ferritin tests were conducted. RESULTS: There was no evidence that
      the intervention had an effect on anemia incidence, which was 66.5% in the
      intervention group and 61.8% in the control group. There was also no evidence of
      any difference between the groups in the prevalence of iron deficiency anemia or
      of iron deficiency. However, a higher percentage of children in the intervention
      group were exclusively breastfed at 4 and 6 months, and breastfed at 6 and 12
      months. Intervention group children also consumed more meat and were fed diets
      with better iron bioavailability and consumed less cow's milk and calcium than
      children from the control group. CONCLUSION: This intervention had no effect on
      the prevalence of anemia, iron deficiency or iron deficiency anemia. Clinical
      trial registry identification number: NCT00629629.

PMID- 22159305
TI  - High internal phase emulsion gels (HIPE-gels) from polymer dispersions reinforced
      with quadruple hydrogen bond functionality.
AB  - A convenient route to organogels templated by high internal phase emulsions has
      been developed. Key is the use of a waterborne polymer latex loaded with a
      multiple hydrogen bond (MHB) functionality that becomes disentangled and
      transfers across the oil-water interface forming a gel network in the oil phase
      via hydrogen bond interactions.

PMID- 22159306
TI  - Temporary restriction of right ventricle-pulmonary artery conduit flow using
      haemostatic clips following Norwood I reconstruction: potential for improved
      outcomes.
AB  - Improved outcomes of the Norwood procedure in hypoplastic left heart syndrome
      have been achieved by the manipulation of the pulmonary:systemic flow ratio
      (Qp:Qs) in the early post-operative period, with focus on improving systemic
      perfusion. As an extension of this Qp:Qs-limiting strategy, we evolved a novel
      surgical technique to achieve transient flow restriction in the right ventricle
      pulmonary artery (RV-PA) conduit for the first 48 h, using haemostatic clips, in
      a cohort of patients and compared the early outcomes with a non-clipped cohort.
      Clips were subsequently removed at 48 h at the time of definitive chest closure.
      We performed RV-PA shunt flow clipping in 37 patients; 75 historical controls had
      not received clips. Groups were matched for weight, size of ascending aorta,
      anatomy and circulatory arrest times. Thirty-day mortality was lower in the
      clipped cohort (2 of 37; 5.4%) versus the unclipped cohort (10 of 75; 13.3%). The
      minimum blood lactate levels within the first 24 h post-surgery in the unclipped
      group were significantly higher (P = 0.049), with a significantly lower Qp:Qs in
      the first 6 h in the clipped patients. These data suggest that limiting Qp:Qs in
      the early post-operative period following the Norwood procedure may help in the
      post-operative management of these difficult patients. These results warrant
      further study.

PMID- 22159307
TI  - Cavitary lung cancer presenting as subcutaneous emphysema on the contralateral
      side.
AB  - Bronchocutaneous fistula is an extremely rare complication of lung cancer and is
      frequently seen following biopsy or radiotherapy. A 67-year old male patient was
      administered to our hospital due to sudden onset of shortness of breath and
      subcutaneous emphysema on the right side. Chest computed tomography revealed a
      cavitary lesion in the left upper lobe in connection with the subcutaneous
      emphysema on the right side through sternum and anterior chest wall. The
      pathological examination of the biopsy performed during tube insertion revealed a
      well-differentiated squamous cell carcinoma of the lung. The patient was referred
      for adjuvant therapy to local oncology hospital. He passed away 9 months
      following diagnosis.

PMID- 22159308
TI  - After-effects of lithium-mediated alumination of 3-iodoanisole: isolation of
      molecular salt elimination and trapped-benzyne products.
AB  - Gaining a deeper understanding of the modus operandi of heterometallic lithium
      aluminate bases towards deprotonative metallation of substituted aromatic
      substrates, we have studied the reactions and their aftermath between our
      recently developed bis-amido base '(i)Bu(2)Al(MU-TMP)(2)Li'3 and 3-halogenated
      anisoles. Ortho-metallation of 3-iodoanisole with 3 results in a delicately
      poised heterometallic intermediate whose breakdown into homometallic species and
      benzyne cannot be suppressed, even at low temperature or in a non-polar solvent
      (hexane). Homometallic components [LiI.TMP(H)](4) (5) and (i)Bu(2)Al(TMP).THF (6)
      have been isolated while the reactive benzyne intermediate has been trapped via
      Diels-Alder cyclization with 1,3-diphenylisobenzofuran yielding 1-methoxy-9-10
      diphenyl-9-10-epoxyanthracene (7). In polar THF solution, nucleophilic addition
      of LiTMP across the benzyne functionality followed by electrophilic quenching
      with iodine yields the trisubstituted aromatic species 1-(2-iodo-3-methoxyphenyl)
      2,2,6,6-tetramethylpiperidide (8). Compounds 5-8 have been characterized by
      single-crystal X-ray diffraction in the solid state and multinuclear NMR
      spectroscopy in solution. By considering these collated results, a plausible
      reaction mechanism has been proposed for the breakdown of the aforementioned
      intermediate bimetallic framework. Interestingly, the metallation reaction can be
      controlled by changing to 3-chloroanisole with an excess of base 3, as evidenced
      by electrophilically trapping the deprotonated aromatic with iodine to give 2
      iodo-3-chloroanisole (9).

PMID- 22159309
TI  - Structural and thermodynamic features of covalent conjugates of sodium caseinate
      with maltodextrins underlying their functionality.
AB  - The sodium caseinate (SCN)-maltodextrin (MD) covalent conjugates were prepared by
      a food-grade process involving the first step of the Maillard reaction. The
      covalent conjugates were prepared with different weight ratios of biopolymers
      (R(MD : SCN) = 0.4; 1; 2; 5) in the system using maltodextrins of strongly
      different dextrose equivalents (DE), i.e., DE = 2 and 10. We have observed that
      the covalent conjugation of SCN with MD, in contrast to their simple mixing,
      improved the protein solubility in an aqueous medium in a wide pH range that was
      more pronounced in the vicinity of the SCN isoelectric point (pH 3.8-4.4). The
      extent of SCN solubility was mainly governed by the weight/molar ratio of the
      biopolymers in the covalent conjugates, R(MD : SCN). Data of static multiangle
      laser light scattering showed that the revealed increase in the solubility of the
      conjugates could be predominantly attributable to the dramatic increase in their
      thermodynamic affinity for an aqueous medium. Which was most pronounced for the
      maltodextrin with the higher DE (DE = 10). The direct relationship between the
      increase in the solubility of the conjugates and the increase in their foaming
      ability, as compared against SCN, has been revealed as a rule both at neutral pH
      and at the pI. In addition, the found improvement in the protein foaming ability
      was also defined by both the weight/molar ratio (R(MD : SCN)) and the dextrose
      equivalent of the maltodextrins attached to the protein.

PMID- 22159310
TI  - A bienzymatic amperometric immunosensor exploiting supramolecular construction
      for ultrasensitive protein detection.
AB  - Self-assembly of a ferrocene-appended polymer bearing an antigen fragment and
      lactate oxidase on a cyclodextrin-modified surface provides a highly sensitive,
      easy-to-operate and self-sufficient immunosensor.

PMID- 22159311
TI  - A highly selective and sensitive BODIPY-based colourimetric and turn-on
      fluorescent sensor for Hg2+ ions.
AB  - A series of monostyryl boron dipyrromethenes appended with an NO(4), NO(2)S(2),
      N(3)O(4), or N(3)O(2)S(2)-type ligand have been prepared and characterised. While
      the UV-Vis spectra of the former three compounds in CH(3)CN/H(2)O (2 : 3 v/v) do
      not respond towards a wide range of metal ions, the derivative with an
      N(3)O(2)S(2)-ligand exhibits a highly selective and sensitive spectral response
      towards Hg(2+) ions. The absorption band is blue-shifted by 40 nm due to
      inhibition of the intramolecular charge transfer process upon metal complexation.
      The fluorescence is also turned on giving a strong emission band at 572 nm. The
      colour changes can be easily detected by the naked eye. The results suggest that
      this compound serves as a promising colourimetric and fluorescent sensor for
      Hg(2+) ions in this mixed aqueous medium.

PMID- 22159312
TI  - Synthesis, structural investigation and computational modelling of water-binding
      aquafoldamers.
AB  - Detailed studies on water-binding aquafoldamers are presented that illustrate the
      potential use of the elongated larger aquafoldamers for recognizing larger water
      clusters of diverse topologies. A novel self-trapping dimerization mode involving
      two tetramer molecules is proposed, which is consistent with the obtained varying
      experimental evidences.

PMID- 22159313
TI  - Growth differentiation factor-9 expression is inversely correlated with an
      aggressive behaviour in human bladder cancer cells.
AB  - Growth differentiation factor-9 (GDF-9) is a family member of bone morphogenetic
      proteins (BMPs), which belong to the TGF-beta superfamily. There has been a
      recent surge of interest in the role of growth differentiation factors and other
      BMPs in the development and spread of cancer. However, the role of GDF-9 in
      bladder cancer remains unknown. The present study investigated the expression of
      GDF-9 in normal and malignant human bladder tissue and its molecular interactions
      within bladder cancer cells. The expression of GDF-9 in human bladder tissues and
      bladder cancer cell lines was assessed at both the mRNA and protein levels using
      RT-PCR and immunohistochemistry, respectively. Full-length GDF-9 cDNA was
      amplified from normal mammary tissues. GDF-9 was overexpressed in bladder cancer
      cell lines using a mammalian expression construct. The effect of GDF-9 on
      cellular functions, was examined in bladder cancer cells overexpressing GDF-9
      using a variety of in vitro assays. In normal bladder tissues, stronger staining
      of GDF-9 was seen in transitional cells, both in the cytoplasm and in the
      nucleus. In contrast, the staining of GDF-9 was notably weak or absent in cancer
      cells of tumour tissues. Similarly, the bladder cancer cell lines RT112 and
      EJ138, expressed very low levels of GDF-9. Moreover, overexpression of GDF-9
      reduced the growth, adhesion and migration of bladder cell lines in vitro.
      However, the overexpression of GDF-9 had little bearing on the invasion of
      bladder cell lines in vitro. In conclusion, GDF-9 is expressed at lower levels in
      human bladder cancer cells compared with normal transitional cells of the
      bladder. GDF-9 levels are inversely correlated with the growth, adhesion and
      migration of bladder cancer cells in vitro. The results of the present study
      suggest that GDF-9 is a potential tumour suppressor in human bladder cancer.

PMID- 22159314
TI  - The metabolic syndrome: a definition dilemma.

PMID- 22159315
TI  - Prevalence of asymptomatic left ventricular systolic dysfunction in hypertensive
      Nigerians: echocardiographic study of 832 subjects.
AB  - BACKGROUND: We sought to determine the prevalence of echocardiographically
      determined left ventricular systolic dysfunction in asymptomatic hypertensive
      subjects seen in Abeokuta, Nigeria. METHODS: Echocardiography was performed in
      832 consecutive hypertensive subjects referred for cardiac evaluation over a
      three-year period. RESULTS: Data were obtained in 832 subjects (50.1% women) aged
      56.0 +/- 12.7 years (men 56.9 +/- 13.3 years, women 55.0 +/- 12.0 years, range 15
      88). The prevalence of left ventricular systolic dysfunction (LVSD) was 18.1% in
      the study population (mild LVSD = 9.6%, moderate LVSD = 3.7% and severe LVSD =
      4.8%). In a multivariate analysis, male gender, body mass index and LV mass were
      the predictors of LVSD. CONCLUSION: Significant numbers of hypertensive subjects
      in this study had varying degrees of left ventricular systolic dysfunction. Early
      introduction of disease-modifying drugs in these patients, such as angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers may retard or
      prevent the progression to overt heart failure.

PMID- 22159316
TI  - Prevalence of the metabolic syndrome in people of Asian Indian origin: outcomes
      by definitions.
AB  - BACKGROUND: The prevalence of the metabolic syndrome (MS) is high among south
      Asian Indians. In order to better comprehend the MS, its definition and
      modifications require region-specific cut-off values and common minimum criteria
      for people of Indian origin. METHODS: To define the MS, the criteria as defined
      in the National Cholesterol Education Program (NCEP): expert panel on detection,
      evaluation, and treatment of high blood cholesterol in adults (Adult Treatment
      Panel III) (ATP III 2001), followed by the modified ATP III of 2005 were used,
      along with a modified version specific to the people of south Asian origin (ATP
      III SAS, 2009). RESULTS: The three definitions showed differences in prevalence
      of the MS among the adult Asian Indians. According to the criteria of NCEP ATP
      III 2001, the prevalence was found to be 32.3%. Using the modified ATP III 2005,
      the prevalence was 48.3%, and for south Asian-specific (SAS) ATP III, it was
      31.4%. For all three definitions, females had a considerably higher prevalence of
      the MS than males. It was also observed that that a large number of individuals
      were misclassified due to lack of common minimum criteria. CONCLUSION: In order
      to curb the growing threat of the MS, and to aid clinical management among people
      of Indian origin, a more comprehensive definition of the MS is urgently required.

PMID- 22159317
TI  - Down syndrome and congenital heart disease: why the regional difference as
      observed in the Libyan experience?
AB  - BACKGROUND: Children with Down syndrome (DS) have about a 40 to 50% incidence of
      congenital heart disease (CHD). The objectives of this study were to evaluate the
      distribution and frequency of CHD patterns in Libyan children with DS. METHODS:
      All patients with DS who were referred to the cardiology clinic between January
      1995 and December 2008 were reviewed. RESULTS: Of the 1 193 patients reviewed,
      537 (45%) had an associated CHD. Overall there were 349 (65%) patients who had a
      single cardiac lesion, and 188 (35%) had multiple cardiac lesions. The most
      common isolated cardiac lesion was atrial septal defect (ASD), found in 125 (23%)
      patients, followed by atrioventricular septal defect (AVSD) in 103 (19%), and
      ventricular septal defect (VSD) in 76 (14%). CONCLUSION: Atrial septal defect was
      the most common cardiac lesion. The distribution of CHDs in Libyan children with
      DS was similar to what has been reported internationally, but the frequency was
      not compared with international rates.

PMID- 22159318
TI  - Diagnosis and follow up of patients with primary cardiac tumours: a single-centre
      experience of myxomas.
AB  - OBJECTIVE: In this study, 12 patients who were diagnosed as having cardiac
      tumours and were operated on in the Department of Cardiovascular Surgery
      following referral from the Department of Cardiology were enrolled between
      January 1995 and October 2007. METHODS: The symptoms, clinical findings,
      diagnostic methods, localisation of masses and surgical applications were
      recorded retrospectively. RESULTS: There were 10 female (83%) and two (17%) male
      patients; their ages ranged from 35 to 70 years (mean 68.7 years). Twelve
      patients were diagnosed with myxomas, nine of which were located within the left
      atrium and three in the right atrium. The most common symptoms at clinical
      presentation were those associated with heart failure or embolisation. Diagnosis
      of the tumours was made by echocardiography in all patients. The masses were
      completely resected in eight patients and the interatrial septae were partially
      excised with mass resection in two patients. The defect was reconstructed with a
      pericardial patch in one of the patients, and primarily reconstructed in the
      other. We carried out debridement with mass resection in another case. Femoro
      popliteal aorto-iliac thrombo-endarterectomy was performed with mass resection in
      a further case. CONCLUSION: Atrial myxomas are the most common primary cardiac
      tumours. They can cause valvular or inflow-outflow tract obstruction, thrombo
      embolism, arrhythmias, or pericardial disorders. Most atrial myxomas are benign
      but due to non-specific symptoms, early diagnosis may be a challenge and they
      must be removed by surgical resection. Diagnosis and follow up with the
      collaboration of cardiology and cardiovascular surgery departments is important
      for meticulous care of these patients.

PMID- 22159319
TI  - Role of stromal-derived factor-1<alpha>/CXCR4 in neo-intimal repair.
AB  - Neo-intimal hyperplasia is one of the major causes of restenosis in which stromal
      cell-derived factor-1<alpha> (SDF-1alpha) and its receptor CXCR4 play an
      important role. In a rat common carotid artery balloon injury model, the number
      of CD34(+)CXCR4(+) cells was significantly increased immediately after injury (p
      < 0.01), followed by a gradual decrease to baseline seven days after the injury.
      Furthermore, the plasma (SDF-1alpha) level was markedly elevated, and peaked 24
      hours after injury (p < 0.01), followed by a rapid decrease to baseline level
      seven days after the injury. In the injured common carotid artery, the mRNA
      expression of (SDF-1alpha) was elevated immediately after injury, followed by a
      gradual decline, but that of CXCR4 was increased four days after injury. Immuno
      histochemistry displayed CXCR4-positive staining one day after injury, which then
      gradually increased and continued for at least one month. In addition,
      administration of AMD3100 (200 ng/kg, i.p.), a CXCR4 antagonist, did not affect
      the number of CD34(+)CXCR4(+) cells, the elevated level of plasma (SDF-1alpha)
      and expression of (SDF-1alpha) mRNA.  The expression of CXCR4 mRNA and protein
      however was markedly decreased, and detectable CXCR4-positive cells occurred four
      days after injury, followed by a decreased intensity of staining. We also found
      that, three months after balloon injury, stenosis of the carotid artery intima in
      the group that received AMD3100 was significantly less than in the untreated
      group (p < 0.05). Therefore, (SDF-1alpha)/CXCR4 played a crucial role in the
      intimal hyperplasia, and restenosis may have be attenuated after inhibition of
      CD34(+)CXCR4(+) cells in the intima.

PMID- 22159320
TI  - The effect of mebudipine on cardiac function and activity of the myocardial
      nitric oxide system in ischaemia-reperfusion injury in rats.
AB  - OBJECTIVES: Previous studies have suggested that failure of the synthesis of
      nitric oxide is involved in the pathophysiology of myocardial ischaemia
      reperfusion injury. In this study, we investigated the effect of mebudipine, a
      new dihydropyridine calcium channel blocker, on cardiac function and activity of
      the myocardial nitric oxide system in ischaemia-reperfusion injury in isolated
      rat hearts. METHODS: Forty male Wistar rats (250-300 g) were divided into four
      groups (n = 10): sham, control, vehicle and drug groups. The animals were
      anesthetised with sodium pentobarbital (6 mg/kg intraperitoneal). The hearts were
      quickly removed, mounted on a Longendorff apparatus and perfused with Krebs
      Henseleit solution under constant pressure at 37 degrees C. After 20 min
      stabilisation period, the ischaemic groups received 30 min global ischaemia and
      120 min reperfusion. For the drug and vehicle groups, before ischaemia the hearts
      were perfused with mebudipine (10(-3) uM) or ethanol-enriched solution (0.01%)
      for 25 min, respectively. Myocardial function, and creatine kinase, lactate
      dehydrogenase and total nitric oxide metabolite (nitrite and nitrate) levels were
      analysed. RESULTS: Cardiac functions had recovered significantly in the
      mebudipine group (p < 0.01). Furthermore, mebudipine remarkably reduced the
      levels of lactate dehydrogenase and creatine kinase in the coronary effluent and
      increased myocardial nitric oxide metabolite levels compared with the control
      group. CONCLUSION: Our results indicate that mebudipine reduced the intensity of
      myocardial ischaemia-reperfusion injury, and that activation of the myocardial
      nitric oxide system played an important role in this regard.

PMID- 22159321
TI  - Analysis of omega-3 fatty acid content of South African fish oil supplements.
AB  - INTRODUCTION: Substantial evidence describes the protective effects of marine
      derived omega-3 (n-3) polyunsaturated fatty acids (PUFA) on cardiovascular
      diseases as well as many other conditions. Numerous fatty acid preparations are
      marketed for supplementing the Western diet, which is low in n-3 fats. Since
      these preparations may vary in their n-3 PUFA content, we tested 45 commercially
      available products on the South African market for their fatty acid composition.
      METHOD: Forty-five commercially available n-3 fatty acid supplements were
      analysed using gas-liquid chromatography to determine their fatty acid content.
      RESULTS: More than half of the n-3 supplements available on the South African
      market contained <= 89% of the claimed content of EPA and/or DHA as stated on the
      product labels. To meet ISSFAL's recommendation of 500 mg EPA + DHA/day can cost
      consumers between R2 and R5 per person per day (R60 to R150 p/p/month). Regarding
      rancidity, the majority of capsules contained conjugated diene (CD) levels higher
      than that of vegetable oil obtained from opened containers (three months) used
      for domestic cooking purposes, despite the addition of vitamin E as antioxidant.
      CONCLUSION: Since no formal regulatory structure for dietary supplements
      currently exists in South Africa, consumers depend on self-regulation within the
      nutraceutical industry for assurance of product quality, consistency, potency and
      purity. Our results indicate that more than half of the n-3 fatty acid
      supplements on the South African market do not contain the claimed EPA and/or DHA
      contents as stated on product labels, and they contained CD levels higher than
      that in unused vegetable oils obtained from opened containers used for domestic
      cooking purposes.

PMID- 22159322
TI  - Potentially increasing rates of hypertension in women of childbearing age and
      during pregnancy--be prepared!
AB  - The incidence of hypertension in young women is likely to increase in the near
      future because of the rising rates of the metabolic syndrome, obesity and
      dyslipidaemia worldwide. Consequently, more women will be on antihypertensive
      agents, which have the potential for teratogenicity. It is also likely that the
      increasing number of young women with essential hypertension who become pregnant
      will develop pregnancy-specific disorders such as pre-eclampsia. Health
      professionals should be aware of the effects of hypertension in women during the
      childbearing years, as well as the impact of pre-eclampsia on cardiovascular
      disease in later life. Pre-conception counselling skills, and knowledge on the
      use of antihypertensives and the changes that occur during pregnancy should be
      added to the clinical armamentarium of all health professionals.

PMID- 22159323
TI  - A rare complication after coronary artery bypass graft surgery: Ogilvie's
      syndrome.
AB  - Gastrointestinal (GI) complications occur in less than 2% of patients undergoing
      open-heart surgery. Acute colonic pseudo-obstruction, known as Ogilvie's
      syndrome, is also a rare complication encountered in 0.046% of patients
      undergoing coronary artery bypass graft surgery. It is characterised by massive
      colonic dilatation without mechanical obstruction in patients with underlying
      medical or surgical conditions. In this report we describe a patient who suffered
      from acute renal failure requiring haemodialysis, and subsequently Ogilvie's
      syndrome, which was treated with high-dose neostigmine.

PMID- 22159324
TI  - Anaesthesia for emergency Caesarean section in a patient with peripartum
      cardiomypathy.
AB  - Peripartum cardiomyopathy (PPCM) is defined as the onset of acute heart failure
      without demonstrable cause in the last trimester of pregnancy or within the first
      six months after delivery. We report a case of PPCM (LVEF < 39%) in a 30-year-old
      housekeeper requiring emergency Caesarean section, who was successfully managed
      with combined spinal-epidural anesthesia, using low-dose fentanyl for the spinal
      anesthesia.

PMID- 22159325
TI  - Diagnostic assessment of prosthetic mitral valve thrombosis by real-time three
      dimensional transoesophageal echocardiography and successful thrombolytic
      treatment.
AB  - Prosthetic valve thrombosis (PVT) is a rare but serious complication of valve
      replacement, most often encountered with mechanical prostheses. The different
      therapeutic modalities for PVT (fibrinolysis with heparin treatment or surgery)
      will largely be influenced by the presence of valvular obstruction, the valve
      location (left or right sided), the patient's clinical status, the existence of
      and expertise in therapeutic modalities at the institution, and the patient's
      decision. This report describes a patient with thrombosis of a prosthetic mitral
      valve, which was successfully treated with recombinant streptokinase in a
      hospital without cardiac surgery. In this context, the authors present the real
      time transoesophageal echocardiographic appearance of this complication, and give
      a brief review of the literature.

PMID- 22159326
TI  - Dramatic reductions in plaque volumes on maximum statin therapy.

PMID- 22159327
TI  - Raft of rivaroxaban good news from the USA, implications for South African
      clinical practice.

PMID- 22159328
TI  - Medical devices in cardiovascular medicine.
AB  - Global PANORAMA study collects largest database on 10,000 patients from the
      Middle East and Africa.

PMID- 22159329
TI  - Marine fungal metabolite 1386A alters the microRNA profile in MCF-7 breast cancer
      cells.
AB  - Marine fungal metabolite 1386A is a newly identified small molecular compound
      extracted from the mangrove fungus 1386A in the South China Sea. Preliminary
      experiments have demonstrated its amazing cytotoxity to cancer cells, while the
      mechanism remains poorly understood. microRNAs (miRNAs) are a newly identified
      class of small regulatory RNAs which play an important role in gene regulation at
      the post-transcriptional level. They usually function as oncogenes or tumor
      suppressors and are related to drug sensitivity and resistance. We aimed to test
      the hypothesis that the potential antineoplastic compound, 1386A, alters the
      miRNA profile in MCF-7 and whether its unknown mechanism may be predicted by
      analysis of the altered miRNA profile. Cell proliferation was analyzed by MTT
      assay. The alteration of the miRNA expression profile of MCF-7 cells was
      investigated using advanced microarray technology. Silico analysis using
      TargetScan was used to predict the putative targeted transcripts encoding the
      dysregulated miRNAs. 1386A inhibited MCF-7 cell proliferation in a time- and dose
      dependent manner (the IC50 value at 48 h was 17.1 umol/l). 1386A (17.1 umol/l)
      significantly altered the global miRNA expression profile of the MCF-7 cells at
      48 h. Forty-five miRNAs were differentially expressed in MCF-7 cells. Target
      prediction suggested that these miRNAs potentially target many oncogenes and
      tumor-suppressor genes associated with cancer development, progression and
      metastasis. The promising antineoplastic compound marine fungal metabolite 1386A
      alters the miRNA profiles of MCF-7 breast cancer cells. Analyzing the alteration
      of the miRNA profile caused by this potential antineoplastic compound may help to
      predict the unknown mechanism of 1386A.

PMID- 22159330
TI  - Clicking 1,2,4,5-tetrazine and cyclooctynes with tunable reaction rates.
AB  - Substituted tetrazines have been found to undergo facile inverse electron demand
      Diels-Alder reactions with "tunable" reaction rates.

PMID- 22159331
TI  - Utilizing hydrogen bonds and halogen-halogen interactions in the design of uranyl
      hybrid materials.
AB  - Reactions of the uranyl cation (UO(2)(2+)) with 4-halopyridinium ions (X = Cl,
      Br, I) in high halide media (X' = Cl, Br) have produced six novel compounds, the
      structures of which have been determined by single crystal X-ray diffraction
      (XRD). The compounds can be divided into two categories based on the different
      modes of hydrogen bonding and halogen-halogen interactions present in the crystal
      structures, with one group showing approximately Type I halogen-halogen
      interactions and the second showing Type II. Presented is a discussion of the
      relative strengths of the interactions as a function of halogen size.

PMID- 22159332
TI  - A self-assembled, metallo-organic supramolecular frequency doubler.
AB  - The dimeric self-assembly program of a new, multidentate ligand with cuprous ions
      overcomes crystal packing forces, which leads to C(i) symmetry in the solid
      state, to form a no less than partially C(2)-symmetric structure in solution. The
      resulting tetranitro-substituted dicopper(i) metallocyclophane displays an
      exceptionally strong second harmonic frequency response (beta = (3000 +/- 600) *
      10(-30) esu for a fundamental at 800 nm).

PMID- 22159333
TI  - Caveolin-1 as a potential high-risk prostate cancer biomarker.
AB  - Current diagnostic techniques of prostate cancer cannot efficiently distinguish
      the latent and low-risk forms from the high-risk significant forms of prostate
      cancer. Caveolin-1 (Cav-1), except other functions, plays an important role in
      cell transformation and the process of tumorigenesis. Furthermore, Cav-1 is
      involved in metastatic processes. It has also been shown that Cav-1 expression is
      induced under stress conditions, such as oxidative stress. The present study
      focused on the determination of prognostic markers of aggressive (high-grade)
      forms of prostate cancer. We determined serum Cav-1 and serum markers of
      antioxidant activity-glutathione (GSH), 2,2-diphenyl-1-picrylhydrazyl (DPPH),
      Trolox equivalent antioxidant capacity (TEAC), ferric-reducing antioxidant power
      (FRAP), N,N-dimethyl-1,4-diaminobenzene (DMPD), free radicals method (FRK) and
      blue chromium peroxide (Cro) in 97 serum samples (82 prostate cancer patients and
      15 controls). We found insignificant differences in Cav-1 between the sera of
      patients and controls (5.69 in the cancer group vs. 5.42 ng/ml in the control
      group). However, we found a significant (p<0.004) 2.8-fold elevation of Cav-1 in
      high tumour stages (TNM T4) compared to lower stages and a significant positive
      association with histological grading (r=0.29, p=0.028). We also found that in
      patients with high serum Cav-1 the antioxidant capacity of the body is reduced.
      These findings indicate that Cav-1 may be an interesting tool for the prediction
      of disease burden.

PMID- 22159334
TI  - [Alternative treatment methods in otorhinolaryngology].

PMID- 22159336
TI  - [Chinese medicine as vegetative systems biology. Part II: the structure of TCM
      diagnosis].
AB  - This section describes the main features of functional vegetative diagnosis in
      traditional Chinese medicine (TCM). A complete diagnosis comprises four
      components: constitution, agent, orb, and guiding criterion. These are based on a
      stringent, almost mathematically precise theoretical matrix as shown by the
      Heidelberg Model of Chinese Medicine. Accordingly, the core concepts of Chinese
      medicine, yin, yang and the phases, can be made rationally accessible to Western
      doctors as technical terms of vegetative regulation.

PMID- 22159335
TI  - [Chinese medicine as vegetative systems biology. Part I: therapeutic methods].
AB  - Chinese medicine (CM) enjoys increasing popularity in Germany despite doubts
      about whether the measures taken make sense and whether they are safe and
      effective. In quantitative terms, CM de facto has already established itself, but
      very often it is reduced to the level of Asian philosophy in the form of mystical
      philosophical remnants. In this bipartite article we present a short overview of
      CM as a traditional approach to stringent and complex systems biology. Only if
      the internal logic of CM can clearly be appreciated by the Western doctor will
      its increasing integration be successful.

PMID- 22159337
TI  - [Forty years of acupuncture experience in an ENT practice].
AB  - Acupuncture as a complementary method provides optimal conditions for ENT
      specialists, particularly when somatotopic microsystems are used, e.g., ear,
      skull, and oral acupuncture. Via points of these systems, pain conditions and
      functional disorders as well as specific ENT indications (e.g., rhinitis
      pollinosa, sinusitis, pharyngitis) can be treated successfully. Therapy is
      performed quickly and without side effects.

PMID- 22159338
TI  - [Phytomedicine in otorhinolaryngology - evidence-based medicine with medicinal
      plants].
AB  - Phytomedicine has become an increasingly important treatment option for patients
      in the western world. Patients who experienced failure or adverse reactions with
      conventional western medicine often switch to natural and holistic methods. In
      eastern countries, with their long history of traditional medicine, patients
      often resort to herbal preparations as the majority of western medicines are
      unaffordable. The desire of western physicians for evidence-based medicine also
      applies in the sector of phytomedicine. A serious perception of natural products
      in scientific medicine can therefore only be based on data from prospective,
      controlled, randomized double-blind clinical trials. In order to illuminate the
      present scientific foundation of effective and reliable phytomedicine, a
      literature search in PubMed (Medline) was conducted based on inclusion and
      exclusion criteria. The main focus was on the field of otorhinolaryngology.
      Besides the presentation of selected, reliable studies and the evaluation of the
      efficacy of various medicinal plants, shortcomings of selected publications are
      discussed.

PMID- 22159339
TI  - [Is a differentiation between low-level and higher phonological processing in
      primary school children justified?].
AB  - BACKGROUND: Several sensory, perceptual and cognitive processes contribute to
      phonological processing. Distinguishing between low- and high-level phonological
      processing has proven useful in clinical tests (speech and language diagnostics).
      Only in the case of the latter is it necessary to operate consciously with speech
      sounds. This study aims to evaluate whether the aforementioned differentiation
      between low- and high-level phonological processing is justified. MATERIAL AND
      METHODS: A retrospective correlation analysis was carried out using the data from
      85 primary school children (6.7-11.3 years old) on low- and high-level
      phonological processing. RESULTS: Total values showed a moderate to strong
      correlation between the results of low- and high-level phonological processing.
      The subscales showed correlation coefficients below 0.5. DISCUSSION: Results
      confirm that a differentiation between low- and high-level phonological
      processing, as mentioned above, is justified. Future studies will need to clarify
      whether therapeutic strategies which take a differentiation of this kind into
      account are more effective than broad-based or unspecific therapy.

PMID- 22159340
TI  - [QR-Code-what is that?].

PMID- 22159341
TI  - [Medical examination: Preparation for ENT specialisation :  Part 2].

PMID- 22159342
TI  - [Traumatology of the ear and temporal bone].
AB  - In addition to injuries to the pinna otologic traumatology comprises in
      particular injuries of the tympanic membrane and ossicular chain, temporal bone
      fractures together with accompanying impairment of the labyrinth and facial nerve
      as well as acoustic trauma and barotrauma. Depending on the mechanism of injury
      and typical symptoms, such as hemorrhagic otorrhoea, hearing loss, vertigo,
      tinnitus, facial nerve palsy, otoliquorrhea or pseudorhinoliquorrhea, further
      investigations should be planned. The present article provides an overview of the
      necessary further diagnostic measures as well as the therapeutic options
      currently available for all forms of injury mentioned here.

PMID- 22159343
TI  - A green and high energy density asymmetric supercapacitor based on ultrathin MnO2
      nanostructures and functional mesoporous carbon nanotube electrodes.
AB  - A green asymmetric supercapacitor with high energy density has been developed
      using birnessite-type ultrathin porous MnO(2) nanoflowers (UBMNFs) as positive
      electrode and functional mesoporous carbon nanotubes (FMCNTs) as negative
      electrode in 1 M Na(2)SO(4) electrolyte. Both of the electrode materials possess
      excellent electrochemical performances, with high surface areas and narrow pore
      size distributions. More significantly, the assembled asymmetric supercapacitor
      with optimal mass ratio can be cycled reversibly in the high-potential range of 0
      2.0 V and exhibits an excellent energy density as high as 47.4 W h kg(-1), which
      is much higher than those of symmetric supercapacitors based on UBMNFs//UBMNFs
      and FMCNTs//FMCNTs supercapacitors. Furthermore, our asymmetric supercapacitor
      (ASC) device also exhibits a superior cycling stability with 90% retention of the
      initial specific capacitance after 1000 cycles and stable Coulombic efficiency of
      ~98%. These intriguing results exhibit great potential in developing high energy
      density "green supercapacitors" for practical applications.

PMID- 22159344
TI  - Atorvastatin inhibits collar-induced intimal thickening of rat carotid artery:
      effect on C-type natriuretic peptide expression.
AB  - The present study was performed to elucidate the mechanism underlying the anti
      atherogenic action of atorvastatin (ATV). We investigated the effect of ATV on
      intimal thickening of the rat carotid artery induced by collar placement and
      further examined the effect of ATV on the expression of C-type natriuretic
      peptide (CNP), cGMP-dependent protein kinase (PKG) Ialpha and PKG Ibeta in
      carotid arteries. The expression of CNP was examined by enzyme-linked
      immunosorbent assay (ELISA) and quantitative real-time RT-PCR. Western blotting
      was used to determine the expression of PKG Ialpha and PKG Ibeta. After 14 days,
      the collar placement induced a marked neointima formation and a reduction in CNP
      and PKG Ialpha expression. These effects were significantly reversed by ATV
      treatment. However, no obvious changes in PKG Ibeta expression were observed
      throughout the study. In conclusion, the present data suggest that elevation of
      CNP represents an additional mechanism by which ATV treatment may prevent the
      development and progression of atherosclerosis.

PMID- 22159347
TI  - Folk uses and pharmacological properties of Casearia sylvestris: a medicinal
      review.
AB  - Folk uses and scientific investigations have highlighted the importance of
      Casearia sylvestris extracts and their relevant bioactive potential. The aim of
      this work was to review the pharmacological properties of C. sylvestris,
      emphasizing its anti-ulcer, anti-inflammatory, anti-ophidian and antitumor
      potentialities. Ethanolic extracts and essential oil of their leaves have
      antiulcerogenic activity and reduce gastric volume without altering the stomach
      pH, which corroborates their consumption on gastrointestinal disorders. Leaf
      water extracts show phospholipase A(2) inhibitory activity that prevents damage
      effects on the muscular tissue after toxin inoculation. This antiphospholipasic
      action is probably related to the use as an anti-inflammatory, proposing a
      pharmacological blockage similar to that obtained with non-steroidal anti
      inflammatory drugs on arachidonic acid and cyclooxygenase pathways. Bioguided
      assay fractionations lead to the identification of secondary metabolites,
      especially the clerodane diterpenes casearins (A-X) and casearvestrins (A-C),
      compounds with a remarkable cytotoxic and antitumor action. Therefore, the C.
      sylvestris shrub holds a known worldwide pharmacological arsenal by its extensive
      folk utilization, exciting searches for new molecules and a better comprehension
      about biological properties.

PMID- 22159348
TI  - Elastase-induced pulmonary emphysema: insights from experimental models.
AB  - Several distinct stimuli can be used to reproduce histological and functional
      features of human emphysema, a leading cause of disability and death. Since
      cigarette smoke is the main cause of emphysema in humans, experimental researches
      have attempted to reproduce this situation. However, this is an expensive and
      cumbersome method of emphysema induction, and simpler, more efficacious
      alternatives have been sought. Among these approaches, elastolytic enzymes have
      been widely used to reproduce some characteristics of human cigarette smoke
      induced disease, such as: augmentation of airspaces, inflammatory cell influx
      into the lungs, and systemic inflammation. Nevertheless, the use of elastase
      induced emphysema models is still controversial, since the disease pathways
      involved in elastase induction may differ from those occurring in smoke-induced
      emphysema. This indicates that the choice of an emphysema model may impact the
      results of new therapies or drugs being tested. The aim of this review is to
      compare the mechanisms of disease induction in smoke and elastase emphysema
      models, to describe the differences among various elastase models, and to
      establish the advantages and disadvantages of elastase-induced emphysema models.
      More studies are required to shed light on the mechanisms of elastase-induced
      emphysema.

PMID- 22159349
TI  - Computer program for distance learning of pesticide application technology.
AB  - Distance learning presents great potential for mitigating field problems on
      pesticide application technology. Thus, due to the lack of teaching material
      about pesticide spraying technology in the Portuguese language and the increasing
      availability of distance learning, this study developed and evaluated a computer
      program for distance learning about the theory of pesticide spraying technology
      using the tools of information technology. The modules comprising the course,
      named Pulverizar, were: (1) Basic concepts, (2) Factors that affect application,
      (3) Equipments, (4) Spraying nozzles, (5) Sprayer calibration, (6) Aerial
      application, (7) Chemigation, (8) Physical-chemical properties, (9) Formulations,
      (10) Adjuvants, (11) Water quality, and (12) Adequate use of pesticides. The
      program was made available to the public on July 1(st), 2008, hosted at the web
      site www.pulverizar.iciag.ufu.br, and was simple, robust and practical on the
      complementation of traditional teaching for the education of professionals in
      Agricultural Sciences. Mastering pesticide spraying technology by people involved
      in agricultural production can be facilitated by the program Pulverizar, which
      was well accepted in its initial evaluation.

PMID- 22159350
TI  - Poly(ADP-ribose) polymerase-1 in high glucose-induced epithelial-mesenchymal
      transition during peritoneal fibrosis.
AB  - Peritoneal fibrosis is a major complication of continuous ambulatory peritoneal
      dialysis (CAPD). The present study tested the hypothesis that ADP-ribose
      polymerase-1 (PARP-1) may play a role in peritoneal epithelial-mesenchymal
      transition and fibrosis under high glucose conditions. High glucose (126 mmol/l)
      induced peritoneal EMT and fibrosis via the PARP-1 mechanism was examined in the
      primary culture of rat peritoneal mesothelial cells (PMCs) and in the human
      peritoneal mesothelial cell line (HMrSv5) in the presence or absence of a PARP-1
      inhibitor PJ34 (3x10-6 M) or by knocking down PARP-1 with the PARP-1 siRNA
      technique. High glucose significantly increased PARP-1 expression and EMT as
      demonstrated by de novo expression of a mesenchymal marker alpha-SMA and loss of
      epithelial phenotype E-cadherin by both rat and human PMC, resulting in
      peritoneal fibrosis including up-regulation of plasminogen activator inhibitor-1
      (PAI-1), collagen I, and fibronectin mRNA and protein expression. All these
      fibrotic responses induced by high glucose were significantly inhibited by the
      PARP-1 inhibitor PJ34 (all P<0.05) or by knocking down PARP-1 with the siRNA
      technique. Results from this study suggested that high glucose stimulates
      peritoneal EMT and fibrosis via a PARP-1-dependent mechanism, and targeting the
      PARP-1 may represent an alternative therapeutic potential for CAPD-related
      peritoneal fibrosis.

PMID- 22159351
TI  - 'Hemilabile' silyl pincer ligation: platinum group PSiN complexes and triple C-H
      activation to form a (PSiC)Ru carbene complex.
AB  - The first example of PSiN mixed-donor silyl pincer ligation is described. Studies
      involving platinum group metal complexes of [(2-(t)Bu(2)PC(6)H(4))(2
      Me(2)NC(6)H(4))SiMe](-) ((t)Bu-PSiN-Me) confirmed that the ligand amino donor is
      labile. Within the coordination sphere of Ru, (t)Bu-PSiN-Me is transformed into a
      PSiC ligand via multiple C-H bond activation events.

PMID- 22159352
TI  - A giant pericardial cyst.
AB  - Pericardial cysts are rare, benign, congenital anomalies. Most are asymptomatic
      and are found incidentally on chest radiographs. Some may cause  symptoms and
      complications. Giant pericardial cysts are even more rare, and few reports on
      their natural history, presentation and management are available. This report
      describes a giant pericardial cyst that exerted pressure on the heart and lungs
      and was excised  surgically. Subsequently, the patient has been asymptomatic for
      nine years and appears to be in complete remission.

PMID- 22159353
TI  - Right common iliac artery stenosis and stent insertion in Behcet's disease.
AB  - Behcet's disease is a multisystem inflammatory disorder that is classified among
      the vasculitides and can affect all types and sizes of blood vessels.  Vascular
      manifestations of Behcet's disease are venous and arterial occlusion, and
      arterial aneurysms. As vasculitis of the vasa vasorum is the main pathological
      hallmark of Behcet's disease, it is generally seen as superficial thrombo
      phlebitis or  occlusion of the major veins; however arterial obstruction and
      aneurysms may also be seen to a lesser extent. Iliac artery stenosis is highly
      uncommon. Here, a case of common iliac stenosis in a 48-year-old patient with
      Behcet's disease is reported. As the risk of aneurysm during an operation was
      high  in this patient, he was treated with vascular stent implantation. Due to
      stent occlusion two months after the operation, percutaneous transluminal
      angioplasty was performed with  an 8-mm balloon. During the three-year follow up,
      no obstruction was observed.

PMID- 22159354
TI  - Percutaneous closure of a tricuspid paravalvular leak with an Amplatzer duct
      occluder II via antegrade approach.
AB  - Paravalvular leaks are seen after valve-replacement surgery and most patients
      with these leaks are asymptomatic, probably due to the small size of the  leak.
      Nevertheless, a paravalvular leak after tricuspid valve replacement is a rare
      complication and may cause severe haemoylsis and hepatic dysfunction. It is
      usually treated  surgically. There are no data on percutaneous transcatheter
      closure of paravalvular leaks. In this report, we present a successful
      percutaneous closure of a paravalvular leak  using an Amplatzer duct occluder II
      device after a tricuspid valve replacement in a patient with high operative risk
      who had also had mitral and aortic valve  replacements.

PMID- 22159355
TI  - Two-dimensional assembly of tetrahedral chalcogenide clusters with
      tetrakis(imidazolyl)borate ligands.
AB  - A new two-dimensional inorganic-organic hybrid solid, formulated as
      Cd(17)S(4)(SPh)(25)B(im)(4) (SPh = benzenethiolate, im = imidazolate), has been
      synthesized under solvothermal conditions. The structure features a 6(3) network
      with 17-nuclear cadmium clusters linked by B(im)(4)(-) ligands. The compound is a
      semiconductor with the band gap of 2.66 eV and displays a green luminescence upon
      excitation at 390 nm.

PMID- 22159358
TI  - Spontaneous abortion and NSAIDs.

PMID- 22159356
TI  - MicroRNA-205 functions as a tumor suppressor in human glioblastoma cells by
      targeting VEGF-A.
AB  - MicroRNAs (miRNAs) are endogenously small non-coding RNAs which are key post
      transcriptional regulators of gene expression. Deregulation of miRNAs is common
      in human tumorigenesis. We report that miRNA-205 is significantly down-regulated
      in glioma cell lines and tissue specimens. Ectopic expression of miRNA-205
      induces apoptosis, cell cycle arrest, impairs cell viability, clonability and
      invasive properties of glioma cells. We further demonstrate that miRNA-205 can
      specifically suppress expression of VEGF-A by directly interacting with the
      putative miRNA-205 binding site at the 3'-UTR. Identification of VEGF-A as a
      direct target for miRNA-205 may imply that miRNA-205 is a novel target for glioma
      therapy. Taken together, the present study for the first time provides evidence
      that miRNA-205 is a glioma-specific tumor suppressor by targeting VEGF-A.

PMID- 22159361
TI  - Research of the Holiday kind: Tabulating Ingestion of Mocha Solution (TIMS): a
      longitudinal prospective cohort study.
AB  - The annual "Roll Up the Rim to Win" contest at Tim Hortons restaurants provides
      customers the opportunity to win prizes. This study investigated win ratios,
      prize types and patterns of coffee consumption.

PMID- 22159362
TI  - Holiday reading: department of advice: how to ensure that you never get asked to
      present at rounds again.

PMID- 22159363
TI  - [Holiday reading: in other words].

PMID- 22159365
TI  - Research of a Holiday kind: elevators or stairs?
AB  - BACKGROUND: Staff in hospitals frequently travel between floors and choose
      between taking the stairs or elevator. We compared the time savings with these
      two options. METHODS: Four people aged 26-67 years completed 14 trips ranging
      from one to six floors, both ascending and descending. We compared the amount of
      time per floor travelled by stairs and by two banks of elevators. Participants
      reported their fatigue levels using a modified Borg scale. We performed two-way
      analysis of variance to compare the log-transformed data, with participant and
      time of day as independent variables. RESULTS: The mean time taken to travel
      between each floor was 13.1 (standard deviation [SD] 1.7) seconds by stairs and
      37.5 (SD 19.0) and 35.6 (SD 23.1) seconds by the two elevators (F=8.61, p<0.001).
      The difference in time taken to travel by stairs and elevator equaled about 15
      minutes a day. Self-reported fatigue was less than 13 (out of 20) on the Borg
      scale for all participants, and they all stated that they were able to continue
      their duties without resting. The extra time associated with elevator use was
      because of waiting for its arrival. There was a difference in the amount of time
      taken to travel by elevator depending on the time of day and day of the week.
      INTERPRETATION: Taking the stairs rather than the elevator saved about 15 minutes
      each workday. This 3% savings per workday could translate into improved
      productivity as well as increased fitness.

PMID- 22159366
TI  - Holiday reading: department of advice: the art of presenting.

PMID- 22159367
TI  - Holiday reading: satire: "The first thing we do, let's kill all the actuaries".

PMID- 22159368
TI  - Facile, mild and fast thermal-decomposition reduction of graphene oxide in air
      and its application in high-performance lithium batteries.
AB  - We firstly propose a facile, mild and effective thermal-decomposition strategy to
      prepare high-quality graphene at a low temperature of 300  degrees C in only 5
      min under an ambient atmosphere. Applying the advantage of this strategy that
      provides an oxidizing atmosphere, pure V(2)O(5)/graphene composite is
      successfully synthesized and exerts excellent lithium storage properties.

PMID- 22159369
TI  - Monitoring metabolites consumption and secretion in cultured cells using ultra
      performance liquid chromatography quadrupole-time of flight mass spectrometry
      (UPLC-Q-ToF-MS).
AB  - Here we present an ultra-performance liquid chromatography-mass spectrometry
      (UPLC-MS) method for extracellular measurements of known and unexpected
      metabolites in parallel. The method was developed by testing 86 metabolites,
      including amino acids, organic acids, sugars, purines, pyrimidines, vitamins, and
      nucleosides, that can be resolved by combining chromatographic and m/z
      dimensions. Subsequently, a targeted quantitative method was developed for 80
      metabolites. The presented method combines a UPLC approach using hydrophilic
      interaction liquid chromatography (HILIC) and MS detection achieved by a hybrid
      quadrupole-time of flight (Q-ToF) mass spectrometer. The optimal setup was
      achieved by evaluating reproducibility and repeatability of the analytical
      platforms using pooled quality control samples to minimize the drift in
      instrumental performance over time. Then, the method was validated by analyzing
      extracellular metabolites from acute lymphoblastic leukemia cell lines (MOLT-4
      and CCRF-CEM) treated with direct (A-769662) and indirect (AICAR) AMP activated
      kinase (AMPK) activators, monitoring uptake and secretion of the targeted
      compound over time. This analysis pointed towards a perturbed purine and
      pyrimidine catabolism upon AICAR treatment. Our data suggest that the method
      presented can be used for qualitative and quantitative analysis of extracellular
      metabolites and it is suitable for routine applications such as in vitro drug
      screening.

PMID- 22159370
TI  - Ion mobility spectrometry as a high-throughput analytical tool in occupational
      pyrethroid exposure.
AB  - The capabilities of ion mobility spectrometry (IMS) as a high throughput and
      green analytical tool in the occupational health and safety control, using
      pyrethroids as models has been evidenced. The method used for dermal and
      inhalation exposure assessment is based on the passive pyrethroid sampling using
      Teflon membranes, direct thermal extraction of the pyrethroids, and measurement
      of the vaporized analytes by IMS without reagent and solvent consumption. The IMS
      signatures of the studied synthetic pyrethroids under atmospheric pressure
      chemical ionization by investigating the formed negative ion products have been
      obtained. The main advantages of the proposed procedure are related to the
      obtained limits of detection, ranging from 0.08 to 5 ng, the simplicity of
      measurement, the lack of sample treatment, and therefore, solvent consumption and
      waste generation, and finally, the speed of analysis.

PMID- 22159371
TI  - Sequential growth in solution of NiFe Prussian blue coordination network
      nanolayers on Si(100) surfaces.
AB  - Controlling the elaboration of Coordination Networks (CoNet) on surfaces at the
      nanoscale remains a challenge. One suitable technique is the Sequential Growth in
      Solution (SGS), which has the advantage to be simple, cheap and fast. We
      addressed two issues in this article: i) the controlled synthesis of ultra thin
      films of CoNet (thickness lower than 10 nm), and ii) the investigation of the
      influence of the precursors' concentration on the growth process. Si(100) was
      used because it is possible to prepare atomically flat Si-H surfaces, which is
      necessary for the growth of ultrathin films. We used, as a model system, the
      sequential reactions of K(4)[Fe(II)(CN)(6)] and [Ni(II)(H(2)O)(6)]Cl(2) that
      occur by the substitution of the water molecules in the coordination sphere of
      Ni(II) by the nitrogen atoms of ferrocyanide. We demonstrated that the nature of
      the deposited film depends mainly on the relative concentration of the anchoring
      sites versus the precursors' solution. Attenuated Total Reflection Fourier
      Transformed Infra Red (ATR-FTIR), X-ray reflectivity, X-ray Photoelectron
      Spectroscopy (XPS) and Atomic Force Microscopy (AFM) were used to characterize
      the steps of the growth process.

PMID- 22159372
TI  - Enhancement of enterohemorrhagic Escherichia coli O157:H7 stress tolerance via
      pre-heating.
AB  - Enterohemorrhagic Escherichia coli O157:H7 infection causes several hundred cases
      of food poisoning every year in Japan. In severe cases, this type of food
      poisoning can be fatal. In the present study, we examined the induction of HSP70
      in E. coli O157:H7 cells at various temperatures and the thermotolerance of E.
      coli O157:H7 cells alone and in contaminated food following pre-heating. We
      evaluated the possibility that thermotolerance by E. coli O157:H7 increases the
      likelihood of food poisoning. E. coli O157:H7 cells were heated at 43-51  degrees
      C, and the survival rate was examined. The temperature of highest induction of
      HSP70 was used as the pre-heating temperature. We measured the thermotolerance of
      E. coli O157:H7 cells following pre-heating as the survival after heating at 53 
      degrees C (lethal temperature). Additionally, we evaluated the thermotolerance of
      E. coli O157:H7 cells in ground beef following pre-heating. Heating at 47 
      degrees C for 30 min caused the highest induction of HSP70 and this temperature
      was selected as the pre-heating temperature. The survival rate was significantly
      higher for 0-90 min compared to that in cultures incubated at 53  degrees C
      without pre-heating indicating thermotolerance. Additionally, in ground beef,
      thermotolerance in E. coli O157:H7 cells was induced by pre-heating. We showed
      that E. coli O157:H7 cells acquired thermotolerance after pre-heating, which
      significantly increased survival after a lethal temperature, and increased the
      likelihood of food poisoning.

PMID- 22159373
TI  - Development of the Japanese reference man model for age-specific phantoms.
AB  - Recent interest in improving methods for calculating radiation doses to atomic
      bomb survivors necessitates reinforcing the data on masses of organs of the
      Japanese population in 1945, including those that are not calculated by DS02, as
      well as increasing the number of phantoms for different ages. Reference is made
      to published data on the masses of organs in normal Japanese subjects of 0-90 y
      of age with more than 5000 samples during 1970-80, as well as the weight and size
      of the total body. The first Japanese Reference Man model, primarily based on
      these data and following the ICRP Reference Man concept, is briefly explained. It
      provides a set of reference values for males and females of six age groups, i.e.
      3 months, 1, 5, 10, 15 and 20-50 y. To consider the organ masses of the Japanese
      population in 1945, the data during the period 1970-80 are compared with the
      literature data of normal Japanese reported in 1952. Differences between the two
      sets of organ data in adults are discussed in relation to changes in the national
      status of nutrition. Additional organ masses of current interest for the Japanese
      population in 1945 are preliminarily considered.

PMID- 22159375
TI  - Cancer stem cells. From characterization to therapeutic implications.
AB  - The cancer stem cell (CSC), or alternatively referred to as the tumor initiating
      cell (TIC) model, proposes that human cancers are organized in a hierarchical
      structure with the CSC at the apex. Cancer stem cells are functionally defined by
      their ability to self-renew, and to recapitulate the hierarchy of the original
      tumor from which they were derived. Emerging data from the literature suggest
      that CSCs might be the fraction within the tumor that resists conventional
      therapies; hence, the CSC paradigm provides new insight into tumor progression
      and relapse. Herein, we provide literature review of the CSC model, with emphasis
      on the translational and clinical implications of this model.

PMID- 22159374
TI  - Gold nanorod-sphingosine kinase siRNA nanocomplexes: a novel therapeutic tool for
      potent radiosensitization of head and neck cancer.
AB  - Radiation therapy (RT) is an important treatment modality used against a number
      of human cancers, including head and neck squamous cell carcinoma (HNSCC).
      However, most of these cancers have an inherent anti-apoptotic mechanism that
      makes them resistant to radiation therapy. This radioresistance of cancer cells
      necessitates the irradiation of tumor areas with extremely high doses of
      radiation to achieve effective therapy, resulting in damage to normal tissues and
      leading to several treatment related side effects. These side effects
      significantly impair the quality of life of treated patients, and preclude the
      possibility of repeat radiation treatment in patients with tumor recurrence. Our
      previous research has correlated the upregulation of the anti-apoptotic
      sphingosine kinase (SphK1) gene in HNSCC cells with their radioresistance
      properties. In the current study, we hypothesized that by downregulating the
      SphK1 gene using nanotechnology mediated gene silencing, we can render these
      cells more vulnerable to radiation therapy by enabling apoptosis at lower
      radiation doses. We have employed biocompatible gold nanorods (GNRs) as carriers
      of short interfering RNA (siRNA) targeting the SphK1 gene. GNRs play a critical
      role in protecting the siRNA molecules against physiological degradation, as well
      as delivering them inside target cells. Following their synthesis and
      characterization, these nanoplexes were applied to HNSCC cells in culture,
      resulting in the radiosensitization of the treated cells. Furthermore, the GNR
      siRNA nanoplexes were injected intratumorally into subcutaneous HNSCC tumors
      grown in mice, prior to the initiation of radiation therapy in vivo. Subsequent
      exposure of GNR-SphK1siRNA nanoplex-treated tumors to radiation (GNR-SphK1siRNA +
      IRRA) resulted in over 50% tumor regression compared to control GNR-GFPsiRNA
      nanoplex and radiation treated tumors (GNR-GFPsiRNA + IRRA). In addition, we were
      able to induce this tumor regression in nanoplex treated tumors with radiation
      doses much lower than those commonly required in clinical RT. These experiments
      lay the foundation for the development of a nanotechnology-mediated gene
      silencing tool for more potent radiation therapy of a number of human cancers,
      with minimal, if any, toxic side effects.

PMID- 22159376
TI  - Expression of alkaline phosphatase in immortalized murine cementoblasts in
      response to compression-force.
AB  - OBJECTIVE: To determine the effect of compression-force on the expression of
      alkaline phosphatase (ALP), and ALP activity in cementoblasts. METHODS: We
      performed this study in the State Key Laboratory of Oral Diseases, West China
      Stomatology Hospital, Sichuan University, Chengdu, Sichuan, China from October to
      December 2010. We exposed murine immortalized cementoblasts (OCCM-30) to 2000
      ustrain compression-force at a frequency of 0.5 Hz for 1, 3, 6, 12, and 24 hours.
      We assayed the cellular ALP activity after the treatments. We used real-time
      polymerase chain reaction (RT-PCR) and western blot to examine the gene and
      protein expression of ALP in the OCCM-30 cells at each time point. RESULTS: Two
      thousand ustrain compressive force significantly up-regulated the mRNA expression
      of ALP in OCCM-30 cells, which reached a peak at 12 hours loading, and the
      protein expression change of ALP in response to compression-force was consistent
      with the variation of gene level. We also noted marked enhancement of ALP
      activity in OCCM-30 cells during the application of mechanical stress.
      CONCLUSION: The compression-force increased the expression of ALP in OCCM-30
      cells, suggesting that mechanical stimulation may affect the cellular function of
      cementoblasts by regulating ALP expression, which may participate in cementum
      metabolism during orthodontic tooth movement.

PMID- 22159377
TI  - Serum hyaluronic acid level does not reliably differentiate minimal and
      significant liver disease in chronic hepatitis C.
AB  - OBJECTIVE: To evaluate the predictive value of hyaluronic acid (HA) for the
      assessment of liver fibrosis and inflammation in chronic hepatitis C (CHC).
      METHODS: This cross-sectional study was conducted at Ziauddin University,
      Karachi, Pakistan from June 2006 to July 2010. Ninety-eight CHC patients, 52
      (53%) males, and 46 (47%) females, with an age range of 20-60 years (mean 36.0+/
      10.5) were recruited. Liver fibrosis was staged on a 5-point scale, F0 to F4, and
      inflammation was graded on a 4-point scale, A0 to A3. Patients were divided into
      minimal (F<2 and A<2) and significant (F>/=2 or A>/=2) overall disease groups.
      The HA was measured in the serum by ELISA. Diagnostic value was assessed through
      receiver operating characteristic (ROC) curve. RESULTS: Significant liver disease
      was present in 46 (47%) patients. Mean serum HA was significantly different among
      severity groups (p = 0.001). Area under ROC curve for overall disease was 0.716.
      Negative predictive value (NPV) for significant overall disease remained 71% at a
      low HA level of 20 ng/mL. Positive predictive value (PPV) of 85% was obtained at
      60 ng/mL and 100% at 120 ng/mL. Those high levels were present in 15% and 10% of
      the patients. CONCLUSION: Serum HA levels showed a low NPV for significant liver
      disease. An acceptable PPV was found only in a small proportion of the patients.
      Hyaluronic acid may not be regarded as a reliable marker for making treatment
      decisions.

PMID- 22159378
TI  - Plasma total antioxidant capacity and its related factors in Iranian pregnant
      women.
AB  - OBJECTIVE: To determine the plasma total antioxidant capacity (TAC) and its
      related factors in pregnant Iranian women attending maternity clinics. METHODS:
      In a cross-sectional study carried out in Naghavi Maternity Clinic, Shaheed
      Beheshti Specialty and Subspecialty Polyclinic and 10 antenatal centers,
      affiliated to Kashan University of Medical Sciences, Kashan, Iran, we determined
      the plasma TAC and its related factors including maternal age, weight, and body
      mass index (BMI) at the beginning, thirteenth, and twenty-first to twenty-fourth
      weeks of pregnancy, and gestational age at the twenty-first to twenty-fourth
      weeks of pregnancy in 137 primigravid pregnant women, 18-30 years old from
      October 2010 to March 2011. We used multiple linear regression to assess the
      relationship between TAC and its related factors. RESULTS: Plasma TAC in the
      twenty-first to twenty-fourth weeks of pregnancy was 0.75+/-0.11 mmol/l. The BMI
      at the beginning was 25.06+/-4, 25.72+/-4.13 at the thirteenth, and 26.95+/-4.19
      kg/m2 at the twenty-first to twenty-fourth weeks of pregnancy. Multiple
      regression analysis showed that gestational age was inversely associated with the
      plasma TAC (beta: -0.234, p=0.007). Regression analysis also suggested a trend
      toward significant association between maternal age and plasma TAC (beta: 0.150,
      p=0.080), but there was no association between other variables and plasma TAC.
      CONCLUSION: Gestational age was inversely correlated with plasma TAC and maternal
      age had a trend toward significant association with TAC in 18-30 year-old Iranian
      pregnant women in their sixth month of pregnancy.

PMID- 22159379
TI  - Characteristics of patients with fluid extravasation during retrograde
      ureteroscopic holmium laser lithotripsy for renal calculi.
AB  - OBJECTIVE: To explore the risk factors of fluid extravasation during retrograde
      ureteroscopic holmium laser lithotripsy for renal calculi. METHODS: Three hundred
      and twenty-seven patients with renal calculi ranging 10 to 20 mm received
      retrograde ureteroscopic holmium laser lithotripsy at Renmin Hospital of Wuhan
      University, Wuhan, China from January 2004 to December 2010. The clinical records
      were reviewed, and the correlation was studied between various clinical factors
      and fluid extravasation complications during operation. The clinical factors to
      be tested included patients' gender and age (<30, 30-50, and >50 years),
      hydronephrosis degree, previous intervention for renal calculi (none, shock-wave
      lithotripsy, and open surgery), upper urinary tract infection, ureteral access
      sheath placement, and procedure duration (<60, 60-120, and >120 mins). The data
      were processed by SPSS Version 16.0 statistical software, x2 test, and binary
      logistic regression were used for analysis. RESULTS: Fluid extravasation
      complications appeared in 35 patients. Patients' gender, age, and hydronephrosis
      degree were irrelevant to the occurrence of fluid extravasation, while having
      previous open surgery for renal calculi, without ureteral access sheath
      placement, upper urinary tract infection, and long procedure duration were all
      responsible for higher incidence of the complications. CONCLUSION: Reasonable
      selection of patients, effective control of upper urinary tract infection,
      routine ureteral access sheath placement, and controlling procedure duration help
      to decrease the incidence of fluid extravasation complications in retrograde
      ureteroscopic holmium laser lithotripsy for renal calculi.

PMID- 22159380
TI  - One month outcome of ocular related emergencies in a tertiary hospital in Central
      Saudi Arabia.
AB  - OBJECTIVE: To investigate the number and characteristics of patients attending
      the Accident/Emergency (A/E) Department of a tertiary care hospital in Riyadh,
      and to determine their route of referral, and pattern of ocular emergency cases.
      METHODS: A retrospective study was carried out using the records and history of
      all patients attending the A/E at King Abdulaziz University Hospital (KAUH) in
      Riyadh, Kingdom of Saudi Arabia in July 2010. Data collected included time of
      arrival, age, gender, source of referral, principal diagnosis, attending doctor,
      action taken, and discharge plan. RESULTS: A total of 1,412 patients were
      recruited in our study with an average daily attendance of 47 patients. A total
      of 863 (61%) patients were male, and their mean age was 28.2 years. The most
      frequent diagnosis in patients was trauma (382, 27%), followed by conjunctivitis
      (211, 14.9%), lids and lacrimal system (133, 9.4%), retina problems (51, 3.6%),
      glaucoma (30, 2.1%), neuro-ophthalmology (22, 1.6%), keratitis (20, 1.4%),
      uveitis (10, 0.7%), and episcleritis (5, 0.35%). Most cases (77.5%) seen were
      self-referrals. Additionally, 712 (50.4%) of cases were considered as non
      emergency, which are visiting the A/E for dry eye, chalazion, blepharitis, and
      allergy. CONCLUSION: Most cases seen at our ophthalmic A/E had non-urgent
      conditions that could be managed satisfactorily by trained ophthalmic assistants
      under supervision of an ophthalmologist.

PMID- 22159381
TI  - Reverse breech extraction versus head pushing in cesarean section for obstructed
      labor. A comparative study in Yemen.
AB  - OBJECTIVE: To compare the maternal and fetal outcome of 2 different methods of
      delivering the baby during cesarian section when the fetal head is deeply
      engaged. METHODS: A prospective case control study was carried out in the
      Obstetrics and Gynecology Department, Al-Thawra General Hospital, Sana'a, Yemen
      from January to December 2010. A total of 118 women who met our criteria were
      included in the study. They were divided randomly into 2 groups. A study group
      (n=59) was assigned to deliver the baby by reverse breech extraction, and control
      group (n=59) was assigned to deliver by the conventional method. The maternal and
      neonatal outcomes between the 2 groups were compared. RESULTS: Extension of the
      uterine incision occurred in significantly less women using reverse breech
      extraction compared to cephalic delivery (5% versus 40.6%; p=0.0001). It was
      observed that the mean operation time and blood loss in the study group were
      lower than that in the control group (52.9 +/- 5.1, 787 +/- 519 versus 67.2 +/-
      4.7, 1231 +/- 471; p<0.0001). No significant difference between groups was noted
      in the maternal and neonatal outcomes. CONCLUSION: Reverse breech extractions is
      an attractive and safe alternative to the standard method for intraoperative
      disengagement of a deeply impacted fetal head in order to reduce maternal and
      fetal morbidly.

PMID- 22159382
TI  - Secular trend of infant mortality rate during wars and sanctions in Western Iraq.
AB  - OBJECTIVE: To study the infant mortality rate (IMR) trend during wars and
      sanction periods in Western Iraq. METHODS: Data collected from the birth and
      death certificates of Haditha Health Vital Statistics Center, Haditha city
      (80,000 population), Western Iraq, included name, age, gender, residence, and
      infant's place and date of births and deaths, in 5 different sanction and war
      stages of the country from 1987 to 2010, in a study period from July to December,
      2010. The IMRs were analyzed and compared between these stages and with other
      studies. RESULTS: The IMR of last 2 years of the Iraq-Iran war (1980-1988) was
      35.6/1000 and 33.8/1000, this  decreased in the war free period (1989-1990) to
      28.6/1000, then increased during the sanction period (1991-2003) to 46/1000 in
      2002, decreased to 16/1000 in 2006 during no sanctions but increased violence,
      then increased to 24.5/1000 in 2010. Approximately two-thirds of deaths occurred
      during the neonatal period, and one third in the post neonatal periods. Males had
      higher IMR than females, and rural residence higher than urban. CONCLUSION:
      Economic sanctions increased IMR more than wars or violence in Haditha city. When
      compared with other parts of Iraq, and despite the different conflicts that faced
      the country during the 24 studied years, Haditha had a lower IMR, however, this
      was still higher than developed, and many developing countries.

PMID- 22159383
TI  - Impact of tinnitus on the quality of life among Saudi patients.
AB  - OBJECTIVE: To assess the impact of tinnitus on the quality of life of Saudi
      patients, and to compare the findings with those of other studies. METHODS: A
      retrospective chart review of 100 tinnitus patients, who visited the
      Otology/Neurotology Clinic at King Abdulaziz University Hospital, Riyadh, Kingdom
      of Saudi Arabia between January 2008 and December 2010, and completed the 25-item
      Tinnitus Handicap Inventory (THI), was conducted. Age, gender, duration of
      symptoms, laterality, and associated hearing loss were included in the data.
      RESULTS: The mean age of 54 men, and 46 women was 47.1+/-13.1 years. The male
      patients had higher THI total scores, emotional and functional total subscale
      scores as compared with the female patients. Associated hearing loss was present
      in 76% of patients. Patients with a long duration of tinnitus had a significantly
      higher scoring of the emotional (p=0.009), and catastrophic total subscale scores
      (p=0.006) compared with those with a short duration. The risk of a male patient
      experiencing a catastrophic score was 3.15 times higher than that in a female
      patient. Associated hearing loss, and tinnitus over a long duration affected the
      catastrophic subscale scores more than the other subscales. Fifty-one percent of
      the patients were grade 4 in the THI. CONCLUSION: Tinnitus had a negative impact
      on the quality of life of Saudi patients. The THI may be a useful tool for
      screening patients, counseling, and charting treatment progress.

PMID- 22159384
TI  - The burden of ischemic heart disease at a major cardiac center in Central Saudi
      Arabia.
AB  - OBJECTIVE: To estimate the direct medical costs associated with ischemic heart
      disease (IHD) at Prince Sultan Cardiac Center (PSCC) in Riyadh, Saudi Arabia.
      METHODS: This is a prevalence-based prospective observational cost of illness
      study conducted in PSCC, Riyadh, Kingdom of Saudi Arabia between April and June
      2009. All patients diagnosed or suspected of having IHD at admission were
      included. They were followed up until discharge, or performing coronary artery
      bypass graft (CABG), or changing  diagnosis. Clinical data were extracted from
      the patients' computerized database, and combined with the unit cost of services
      to calculate costs. RESULTS: A total of 205 patients were recruited and diagnosed
      with stable angina (SA, 47.8%), unstable angina (USA, 24.4%), ST-segment
      elevation myocardial infarction (STEMI, 19.5%), and non-ST-segment elevation
      myocardial infarction (NSTEMI, 8.3%). Most of the patients were Saudi males, aged
      between 40-75 years. Eighty-seven percent of patients had 2 or more co
      morbidities, and 32% of the patients were obese. The average cost was 40,164
      Saudi Riyals (SAR)/patient (US$10,710). Medication contributed the lowest in the
      costs (3.2%). A cost associated with SA was SAR33,991, USA was SAR35,107, NSTEMI
      was SAR46,585, and STEMI was SAR58,877 per patient. The lowest mean hospital
      length of stay was 6.5 days with SA. The average length of stay increased with
      the number of co-morbidities from 5.67 days (no co-morbidity) to 11.25 days (6 co
      morbidities). CONCLUSION: The IHD is of high economic burden in the country.
      Among IHD types studied, the resource consumption associated to STEMI was the
      highest in terms of costs, and hospital length of stay.

PMID- 22159385
TI  - Assessment of quality of life in patients with type 2 diabetes mellitus in Oman.
AB  - OBJECTIVE: To measure quality of life of type 2 diabetes patients in Oman, and
      examine which patients' socio-demographic and diabetes-related clinical
      characteristics are associated with better quality of life. METHODS: This cross
      sectional study of 200 diabetic subjects was conducted in Sultan Qaboos
      University Hospital, Al-Khod, Oman between April and September 2009. A short form
      of the diabetes quality of life questionnaire (DQoL) was used to elicit indices
      of quality of life on subjects (n=200) seeking consultation at the diabetic
      outpatient clinic. Socio-demographic variables, body mass index (kg/m) and
      clinical parameters relevant for the diagnosis of type 2 diabetes, including
      glycated hemoglobin A1c level, (HbA1c), were also sought. RESULTS: The results
      show that patients with less than 5 years of disease duration and HbA1c less than
      8% reported significantly better overall DQoL. Patients with HbA1c less than 8%
      showed significantly higher glycemic control satisfaction score. The same trend
      was observed in patients with less than 5 years duration of diabetes. Patients
      with ages less than 40 years have significantly better self care adherence scores
      and total score of QoL. CONCLUSION: Patients' reported moderate DQoL, which
      appears to be related to demographics, medical history, and management regimens.
      Patients with HbA1c less than 8% showed significantly higher glycemic control
      satisfaction score. Furthermore, patients who are less than 40 years of age have
      significantly better quality of life compared to other age groups.

PMID- 22159386
TI  - Vitiligo-epidemiological study of 4134 patients at the National Center for
      Vitiligo and Psoriasis in Central Saudi Arabia.
AB  - OBJECTIVE: To assess the clinical patterns, epidemiological profile of vitiligo,
      and its awareness among Saudi nationals. METHODS: A retrospective study was
      conducted among Saudi nationals with a confirmed diagnosis of vitiligo 
      presenting to the National Center for Vitiligo and Psoriasis, Riyadh, Saudi
      Arabia, from August 2002 to August 2006 using a retrospective questionnaire based
      on the history and medical records of patients. RESULTS: Of the 4134 cases, 53.5%
      were females. The mean age of onset of vitiligo was 17.4 years. Vitiligo vulgaris
      was the most common type in 42.3% of cases, 90.5% had no associated autoimmune
      conditions. The family history was positive in 42.8%. Twenty-nine percent
      developed depigmentation on multiple sites, and 68.2% over exposed areas. Nearly
      1912 (46.2%) were not aware of its cause, and 2682 (64.9%) were unaware of
      aggravating factors. Stress as an aggravating factor was considered by 15.1%.
      Herbal treatments were considered very effective by 45.8%. CONCLUSION: Vitiligo
      is affecting Saudi women more than men with an early age of onset. Vitiligo
      vulgaris being the most prevalent form with a high rate of positive family
      history and low rate of associated autoimmune diseases. Knowledge of genetic and
      environmental factors affecting vitiligo is poorly conveyed and explored.

PMID- 22159387
TI  - Research productivity among faculty members at medical and health schools in
      Saudi Arabia. Prevalence, obstacles, and associated factors.
AB  - OBJECTIVE: To identify the prevalence, factors and obstacles affecting research
      productivity among academic staff at medical and health colleges in the Kingdom
      of Saudi Arabia. METHODS: This cross-sectional survey employed self-administered
      questionnaires to collect data on faculty members' profile, research activities,
      and obstacles impeding research productivity. The questionnaires were distributed
      randomly to 500 faculty members, of which 389 (77.8%) completed the questionnaire
      at 10 medical and health colleges during January to April 2011. The data were
      analyzed and presented in a descriptive fashion. RESULTS: Only 150 (38.6%)
      respondents reported published work in the past 2 years. Of these, 80% indicated
      sole-authors research and around a quarter (26%) reported co-authors work. Males
      and young faculty members were more likely to publish research than their
      counterparts. Faculty members who reported involvement in administrative
      activities were less likely to publish. Those who reported supervising
      postgraduate students or had attained training on research methods were more
      likely to produce research. Respondents perceived that lack of time, lack of
      research assistants, lack of funds for research, and being busy with teaching
      load were the most cited obstacles impeding research productivity. CONCLUSION:
      Understanding factors and barriers impeding research productivity is a
      prerequisite for interventions that are directed to promote health services
      research among faculty members in medical schools.

PMID- 22159388
TI  - Hyperphosphatasemia in an adult. Clinical, conventional roentgenographic, and CT
      findings.
AB  - A 47-year-old Saudi deaf lady with short stature presented being unable to walk.
      She had long standing diffuse skeletal deformities, and progressive head
      enlargement. She had markedly elevated serum alkaline phosphatase. The
      radiographic changes were those of hyperphosphatasemia, and the CT scanning of
      the skull, which was not studied before, further elicited the extensive calvarial
      and basilar changes. The various entities of hyperphosphatasemia with and without
      bony changes are reviewed.

PMID- 22159389
TI  - Intranodal angiolipoma.
AB  - Angiolipomas are not uncommon tumors of the soft tissue, but are rarely found in
      other parts of the body. We report a case of intranodal angiolipoma in a 64-year
      old man who presented with right inguinal swelling. Histopathological examination
      showed a tumor composed of mature adipose tissue and prominent vascular
      component, which is consistent with angiolipoma. We conclude that angiolipoma can
      be added to the list of conditions or diseases in the differential diagnosis of
      localized lymphadenopathy.

PMID- 22159390
TI  - Genotoxicity and cytotoxicity of ovine collagen on human dermal fibroblasts.

PMID- 22159391
TI  - A severity score for intraventricular hemorrhage in preterm neonates.

PMID- 22159392
TI  - Bacillus Calmette-Guerins vaccination at birth causing tuberculous granulomatous
      lymphadenitis.

PMID- 22159393
TI  - Comparison of the effects of sedation and general anesthesia in surgically
      assisted rapid palatal expansion.

PMID- 22159394
TI  - Drug susceptibility pattern of Mycobacterium tuberculosis isolates against
      conventional anti-tuberculosis drugs in Dhaka, Bangladesh.

PMID- 22159395
TI  - Microscopy, culture, and sensitive management of uncomplicated urinary tract
      infections in adults in the primary care setting.

PMID- 22159396
TI  - Vitamin A status in wheezing Saudi children.

PMID- 22159397
TI  - Palladium(II)-selenoether complexes as new single source precursors: first
      synthesis of Pd4Se and Pd7Se4 nanoparticles.
AB  - Pd(4)Se and Pd(7)Se(4) nanoparticles (size 38-104 nm), protected by TOP, have
      been obtained for the first time using Pd(II) ligated with selenated primary and
      secondary amines (see 1 and 2) as single source precursors respectively. TEM,
      SEM, powder XRD and photoluminescence have been used to characterize them. 1 and
      2 are also the first Pd(II)-selenoether complexes used for the synthesis of
      nanoparticles containing palladium and selenium.

PMID- 22159398
TI  - Does the time of inactivation of pRb determine the cell of origin of
      retinoblastoma?

PMID- 22159399
TI  - Can vision loss be predicted by a mathematical model of Fuchs dystrophy?

PMID- 22159401
TI  - Keratinocyte growth factor induces matrix metalloproteinase-9 expression and
      correlates with venous invasion in pancreatic cancer.
AB  - Keratinocyte growth factor (KGF), also known as fibroblast growth factor-7, and
      KGF receptor (KGFR) play important roles in the growth of epithelial cells and
      are overexpressed in a variety of malignant epithelial tumors, including
      pancreatic ductal adenocarcinoma (PDAC). We previously reported that co
      expression of KGF and KGFR in PDAC is associated with venous invasion, enhanced
      vascular endothelial growth factor A expression and poor prognosis. Matrix
      metalloproteinase-9 (MMP-9) is known to participate in the degradation of type IV
      collagen, which is a primary component of extracellular matrices in the vascular
      basement membrane. In the present study, we examined the expression and roles of
      KGF, KGFR and MMP-9 in human PDAC cell lines and tissues. Quantitative real-time
      polymerase chain reaction analysis demonstrated the expression of MMP-9 mRNA in
      all eight PDAC cell lines. KGF, KGFR and MMP-9 were, respectively, expressed in
      27 (43%), 23 (37%) and 35 (56%) of 63 patients. Each expression of KGF, KGFR or
      MMP-9 correlated positively with venous invasion. Furthermore, expression of KGF
      or MMP-9 correlated positively with liver metastasis. KGF-positive cases
      exhibited shorter survival than KGF-negative cases, while KGFR and MMP-9
      expression were unrelated to prognosis. Administration of recombinant human KGF
      increased MMP-9 expression in PDAC cells, while transient transfection with short
      hairpin RNAs targeting KGF transcripts reduced MMP-9 expression in PDAC cells.
      Moreover, recombinant human KGF significantly enhanced migration and invasion of
      PDAC cells. These findings suggest that KGF and KGFR promote venous invasion via
      MMP-9 in PDAC, and closely correlate with liver metastasis. The KGF/KGFR pathway
      may be a critical therapeutic target for PDAC metastasis.

PMID- 22159402
TI  - Prognostic determinants of patients with chronic systolic heart failure secondary
      to systemic arterial hypertension.
AB  - BACKGROUND: Systemic arterial hypertension (SAH) is an important cause of chronic
      systolic heart failure (CHF) in underdeveloped countries. It would be desirable
      to know predictors of mortality for patients with this condition in order to
      provide proper scientific treatment. OBJECTIVE: To determine risk factors for all
      cause mortality in patients with CHF secondary to SAH in the current era of heart
      failure therapy for left ventricular systolic dysfunction. METHODS: All patients
      routinely and prospectively followed at the Cardiomyopathy Clinic of our
      Institution from January, 2000 to April, 2008 with the diagnosis of CHF secondary
      to SAH were screened for the study. Cox proportional hazards model was used to
      establish independent predictors of all-cause mortality. RESULTS: One hundred
      thirty patients were included; 74 (57%) were male. Thirty one (24%) patients
      died, 5 (4%) underwent heart transplantation, and 94 (72%) were alive at study
      end. Survival probability at 12, 24, 36, 48, and 60 months was 96%, 93%, 84%,
      79%, and 76%, respectively. Age (Hazard Ratio=1,05, 95% Confidence Interval 95%
      1,01 to 1,08, p value=0,01), left ventricular diastolic dimension (Hazard
      Ratio=1,08; 95% Confidence Interval 1,02 to 1,09; p value=0,003), and B-Blocker
      therapy (Hazard Ratio=0,41; 95% Confidence Interval 0,19 to 0,86; p value=0,02)
      were found to be independent predictors of mortality. CONCLUSION: Age, left
      ventricular diastolic dimension and underuse of Beta-Blocker therapy were
      independent predictors of mortality for patients with CHF secondary to SAH in the
      population studied.

PMID- 22159403
TI  - Cross-cultural adaptation into Brazilian portuguese of the Dietary Sodium
      Restriction Questionnaire (DSRQ).
AB  - BACKGROUND: Sodium restriction is a non-pharmacological measure often recommended
      to patients with heart failure (HF). However, adherence is low, being among the
      most common causes of HF decompensation. The Dietary Sodium Restriction
      Questionnaire (DSRQ) aims at identifying factors that affect adherence to dietary
      sodium restriction by patients with HF. In Brazil, there are no instruments to
      assess these factors. OBJECTIVE: Perform the transcultural adaptation of DSRQ.
      METHODS: Methodological study that involved the following steps: translation,
      synthesis, back-translation, review by an expert committee, pretest of the final
      version and analysis of interobserver agreement. In the pretest, items and their
      understanding were evaluated, as well as internal consistency by Cronbach's
      alpha. The instrument was simultaneously and independently administered by two
      researchers and the kappa test was used for agreement analysis. RESULTS: Only one
      question underwent major semantic and/or cultural alteration. At the pretest,
      Cronbach's alpha for the total obtained was 0.77; for the Attitude, Subjective
      Norm and Behavioral Control scales were obtained, respectively: 0.66, 0.50 and
      0.85. At the agreement step, the Kappa was calculated for 12 of the 16 questions,
      with values ranging from 0.62 to 1.00. In items for which the calculation was not
      possible, the incidence of equal responses ranged from 95% to 97.5%. CONCLUSION:
      Based on the transcultural adaptation of DSRQ, it was possible to propose a
      version of the questionnaire for further evaluation of psychometric properties.

PMID- 22159404
TI  - Interaction between serotoninergic-and beta-adrenergic receptors signaling
      pathways in rat femoral artery.
AB  - BACKGROUND: Coronary heart disease has been widely studied in cardiovascular
      research. However, patients with peripheral artery disease (PAD) have worst
      outcomes compared to those with coronary artery disease. Therefore,
      pharmacological studies using femoral artery are highly relevant for a better
      understanding of the pathophysiologic responses of the PAD. OBJECTIVE: The aim of
      this study was to evaluate the pharmacologic properties of the contractile and
      relaxing agents in rat femoral artery. METHODS: Concentration response curves to
      the contractile phenylephrine (PE) and serotonin (5-HT) and the relaxing agents
      isoproterenol (ISO) and forskolin were obtained in isolated rat femoral artery.
      For relaxing responses, tissues were precontracted with PE or 5-HT. RESULTS: The
      order rank potency in femoral artery was 5-HT > PE for contractile responses. In
      tissues precontracted with 5-HT, relaxing responses to isoproterenol was
      virtually abolished as compared to PE-contracted tissues. Forskolin, a stimulant
      of adenylyl cyclase, partially restored the relaxing response to ISO in 5-HT
      precontracted tissues. CONCLUSION: An interaction between beta-adrenergic- and
      serotoninergic- receptors signaling pathway occurs in femoral artery. Moreover,
      this study provides a new model to study serotoninergic signaling pathway under
      normal and pathological conditions which can help understanding clinical outcomes
      in the PAD.

PMID- 22159405
TI  - microRNA-1301-mediated inhibition of tumorigenesis.
AB  - The relatively recent discovery of microRNAs has added a completely new dimension
      to the study of the regulation of tumor cells, but how they control cell behavior
      remains largely elusive. HepG2 cells were assigned to the miR-1301 group and the
      control group. RT-PCR, Western blotting, wound healing, the Transwell chamber
      migration and MTT assays, and apoptosis detection assays were used to analyze
      cell behavior of HepG2 cells after miR-1301 mimic transfection. Our study showed
      that miR-1301 was downregulated in HepG2 cells, and that miR-1301 inhibited
      migration and invasion of HepG2 cells and promoted cellular apoptosis after
      transfection with miR-1301 mimics. In addition, p53 mRNA and p53 protein
      expression was upregulated, and Bcl-2 and Bcl-xL mRNA and protein expression was
      downregulated in the miR-1301 group. These results indicate that miR-1301 may be
      an inhibitor of tumorigenesis in HepG2 cells.

PMID- 22159406
TI  - Self-association free bifunctional thiourea organocatalysts: synthesis of chiral
      alpha-amino acids via dynamic kinetic resolution of racemic azlactones.
AB  - Concentration-independent high enantioselectivity in the dynamic kinetic
      resolution (DKR) of racemic azlactones affording chiral alpha-aminoesters has
      been achieved using self-association free thiourea-based dimeric cinchona
      alkaloid organocatalysts. Detailed experimental studies and single crystal X-ray
      analysis confirmed that these bifunctional organocatalysts I do not form H-bonded
      self-aggregates in either solution or solid state.

PMID- 22159407
TI  - Carbon nanodots as fluorescence probes for rapid, sensitive, and label-free
      detection of Hg2+ and biothiols in complex matrices.
AB  - In this work, unmodified carbon nanodots are demonstrated as novel and
      environmentally-friendly fluorescence probes for the sensing of Hg(2+) and
      biothiols with high sensitivity and selectivity.

PMID- 22159408
TI  - Facile and mild solution synthesis of Cu2O nanowires and nanotubes driven by
      screw dislocations.
AB  - We report a green synthesis of Cu(2)O nanowires and nanotubes in aqueous solution
      by reducing Cu(2+) to Cu(+) with glucose or fructose via Fehling's reaction. The
      screw dislocation-driven growth of Cu(2)O nanowires and nanotubes is confirmed by
      imaging the dislocation contrast, the Eshelby twist associated with dislocations
      and the spontaneously formed hollow nanotubes.

PMID- 22159409
TI  - A dual-route cascaded model of reading by deaf adults: evidence for grapheme to
      viseme conversion.
AB  - There is an ongoing debate whether deaf individuals access phonology when
      reading, and if so, what impact the ability to access phonology might have on
      reading achievement. However, the debate so far has been theoretically unspecific
      on two accounts: (a) the phonological units deaf individuals may have of oral
      language have not been specified and (b) there seem to be no explicit cognitive
      models specifying how phonology and other factors operate in reading by deaf
      individuals. We propose that deaf individuals have representations of the
      sublexical structure of oral-aural language which are based on mouth shapes and
      that these sublexical units are activated during reading by deaf individuals. We
      specify the sublexical units of deaf German readers as 11 "visemes" and
      incorporate the viseme set into a working model of single-word reading by deaf
      adults based on the dual-route cascaded model of reading aloud by Coltheart,
      Rastle, Perry, Langdon, and Ziegler (2001. DRC: A dual route cascaded model of
      visual word recognition and reading aloud. Psychological Review, 108, 204-256.
      doi: 10.1037//0033-295x.108.1.204). We assessed the indirect route of this model
      by investigating the "pseudo-homoviseme" effect using a lexical decision task in
      deaf German reading adults. We found a main effect of pseudo-homovisemy,
      suggesting that at least some deaf individuals do automatically access sublexical
      structure during single-word reading.

PMID- 22159410
TI  - A novel mono-carbonyl analogue of curcumin induces apoptosis in ovarian carcinoma
      cells via endoplasmic reticulum stress and reactive oxygen species production.
AB  - The aim of the present study was to investigate the apoptosis of human ovarian
      cancer cell lines, A2780 and CP70, induced by a novel curcumin analogue, B19. The
      proliferation of cells was detected with methyl thiazolyl tetrazolium (MTT) assay
      and apoptosis was examined by flow cytometry. Reactive oxygen species (ROS) were
      assessed by the fluorescent indicator DCF-DA. The protein expression of the
      endoplasmic reticulum (ER) stress pathways, GRP78, XBP-1, ATF-4 and CHOP, was
      examined with Western blotting. A growth inhibitory effect was observed after
      treatment with B19 in a dose-dependent manner and with more potential than
      curcumin. At 20 uM, B19 induced significant apoptosis in CP70 cells. Furthermore,
      B19 induced the ER stress response, while curcumin had no effect on ER stress.
      These results suggest that B19 has more effective antitumor properties than
      curcumin, and is associated with the activation of ER stress and ROS in ovarian
      cancer cells.

PMID- 22159411
TI  - Is nevirapine atropisomeric? Experimental and computational evidence for rapid
      conformational inversion.
AB  - The non-nucleoside reverse transcriptase inhibitor nevirapine displays in its
      room temperature (1)H-NMR spectrum signals characteristic of a chiral compound.
      Following suggestions in the recent literature that nevirapine may display
      atropisomerism-and therefore be a chiral compound, due to slow interconversion
      between two enantiomeric conformers-we report the results of an NMR and
      computational study which reveal that while nevirapine does indeed possess two
      stable enantiomeric conformations, they interconvert with a barrier of about 76
      kJ mol(-1) at room temperature. Nevirapine has a half life for enantiomerisation
      at room temperature of the order of seconds, is not atropisomeric, and cannot
      exist as separable enantiomers.

PMID- 22159412
TI  - Linking cytoplasmic dynein and transport of Rab8 vesicles to the midbody during
      cytokinesis by the doublecortin domain-containing 5 protein.
AB  - Completion of mitosis requires microtubule-dependent transport of membranes to
      the midbody. Here, we identified a role in cytokinesis for doublecortin domain
      containing protein 5 (DCDC5), a member of the doublecortin protein superfamily.
      DCDC5 is a microtubule-associated protein expressed in both specific and dynamic
      fashions during mitosis. We show that DCDC5 interacts with cytoplasmic dynein and
      Rab8 (also known as Ras-related protein Rab-8A), as well as with the Rab8
      nucleotide exchange factor Rabin8 (also known as Rab-3A-interacting protein).
      Following DCDC5 knockdown, the durations of the metaphase to anaphase transition
      and cytokinesis, and the proportion of multinucleated cells increases, whereas
      cell viability decreases. Furthermore, knockdown of DCDC5 or addition of a dynein
      inhibitor impairs the entry of Golgi-complex-derived Rab8-positive vesicles to
      the midbody. These findings suggest that DCDC5 plays an important role in
      mediating dynein-dependent transport of Rab8-positive vesicles and in
      coordinating late cytokinesis.

PMID- 22159413
TI  - Characterization of Pax3-expressing cells from adult blood vessels.
AB  - We report expression of Pax3, an important regulator of skeletal muscle stem cell
      behaviour, in the brachial and femoral arteries of adult mice. In these
      contractile arteries of the limb, but not in the elastic arteries of the trunk,
      bands of GFP-positive cells were observed in Pax3(GFP/+) mice. Histological and
      biochemical examination of the vessels, together with clonal analysis after
      purification of Pax3-GFP-positive cells by flow cytometry, established their
      vascular smooth muscle identity. These blood-vessel-derived cells do not respond
      to inducers of other mesodermal cell types, such as bone, however, they can
      contribute to muscle fibre formation when co-cultured with skeletal muscle cells.
      This myogenic conversion depends on the expression of Pax3, but is rare and non
      cell autonomous as it requires cell fusion. Myocardin, which promotes acquisition
      of a mature smooth muscle phenotype in these Pax3-GFP-positive cells, antagonises
      their potential for skeletal muscle differentiation. Genetic manipulation shows
      that myocardin is, however, positively regulated by Pax3, unlike genes for other
      myocardin-related factors, MRTFA, MRTFB or SRF. Expression of Pax3 overlaps with
      that reported for Msx2, which is required for smooth muscle differentiation of
      blood vessel-derived multipotent mesoangioblasts. These observations are
      discussed with respect to the origin and function of Pax3-expressing cells in
      blood vessels, and more general questions of cell fate determination and adult
      cell plasticity and reprogramming.

PMID- 22159414
TI  - MT1-MMP regulates the turnover and endocytosis of extracellular matrix
      fibronectin.
AB  - The extracellular matrix (ECM) is dynamically remodeled by cells during
      development, normal tissue homeostasis and in a variety of disease processes. We
      previously showed that fibronectin is an important regulator of ECM remodeling.
      The deposition and/or polymerization of fibronectin into the ECM controls the
      deposition and stability of other ECM molecules. In addition, agents that inhibit
      fibronectin polymerization promote the turnover of fibronectin fibrils and
      enhance ECM fibronectin endocytosis and intracellular degradation. Endocytosis of
      ECM fibronectin is regulated by beta1 integrins, including alpha5beta1 integrin.
      We have examined the role of extracellular proteases in regulating ECM
      fibronectin turnover. Our data show that membrane type matrix metalloproteinase 1
      (MT1-MMP; also known as MMP14) is a crucial regulator of fibronectin turnover.
      Cells lacking MT1-MMP show reduced turnover and endocytosis of ECM fibronectin.
      MT1-MMP regulates ECM fibronectin remodeling by promoting extracellular cleavage
      of fibronectin and by regulating alpha5beta1-integrin endocytosis. Our data also
      show that fibronectin polymerization stabilizes fibronectin fibrils and inhibits
      ECM fibronectin endocytosis by inhibiting alpha5beta1-integrin endocytosis. These
      data are the first to show that an ECM protein and its modifying enzyme can
      regulate integrin endocytosis. These data also show that integrin trafficking
      plays a major role in modulating ECM fibronectin remodeling. The dual dependence
      of ECM fibronectin turnover on extracellular proteolysis and endocytosis
      highlights the complex regulatory mechanisms that control ECM remodeling to
      ensure maintenance of proper tissue function.

PMID- 22159415
TI  - Differential regulation of adherens junction dynamics during apical-basal
      polarization.
AB  - Adherens junctions (AJs) in epithelial cells are constantly turning over to
      modulate adhesion properties under various physiological and developmental
      contexts, but how such AJ dynamics are regulated during the apical-basal
      polarization of primary epithelia remains unclear. Here, we used new and
      genetically validated GFP markers of Drosophila E-cadherin (DE-cadherin,
      hereafter referred to as DE-Cad) and beta-catenin (Armadillo, Arm) to
      quantitatively assay the in vivo dynamics of biosynthetic turnover and membrane
      redistribution by fluorescence recovery after photobleaching (FRAP) assays. Our
      data showed that membrane DE-Cad and Arm in AJs of polarizing epithelial cells
      had much faster biosynthetic turnover than in polarized cells. Fast biosynthetic
      turnover of membrane DE-Cad is independent of actin- and dynamin-based
      trafficking, but is microtubule-dependent. Furthermore, Arm in AJs of polarizing
      cells showed a faster and diffusion-based membrane redistribution that was both
      quantitatively and qualitatively different from the slower and exchange-based DE
      Cad membrane distribution, indicating that the association of Arm with DE-Cad is
      more dynamic in polarizing cells, and only becomes stable in polarized epithelial
      cells. Consistently, biochemical assays showed that the binding of Arm to DE-Cad
      is weaker in polarizing cells than in polarized cells. Our data revealed that the
      molecular interaction between DE-Cad and Arm is modulated during apical-basal
      polarization, suggesting a new mechanism that might be crucial for establishing
      apical-basal polarity through regulating the AJ dynamics.

PMID- 22159416
TI  - SrGAP3 interacts with lamellipodin at the cell membrane and regulates Rac
      dependent cellular protrusions.
AB  - SrGAP3/MEGAP is a member of the Slit-Robo GAP (srGAP) family and is implicated in
      repulsive axon guidance and neuronal migration through Slit-Robo-mediated signal
      transduction. Here we describe an inhibitory role of srGAP3 on actin dynamics,
      specifically on lamellipodia formation. We show that the F-BAR domain localizes
      srGAP3 to the leading edge of cellular protrusions whereas the SH3 domain is
      important for focal adhesion targeting. We report on a novel srGAP3 interaction
      partner, lamellipodin, which localizes with srGAP3 at the leading edge. Live-cell
      analyses revealed that srGAP3 influences lamellipodin-evoked lamellipodial
      dynamics. Furthermore, we show that mouse embryonic fibroblasts derived from
      homozygous srGAP3-knockout embryos display an increased cell area and
      lamellipodia formation that can be blocked by shRNA-mediated knockdown of
      lamellipodin.

PMID- 22159417
TI  - Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase
      Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor
      cells.
AB  - Chondroitin sulfates (CSs) and dermatan sulfates (DSs) are enriched in the
      microenvironment of neural stem cells (NSCs) during development and in the adult
      neurogenic niche, and have been implicated in mechanisms governing neural
      precursor migration, proliferation and differentiation. In contrast to previous
      studies, in which a chondroitinaseABC-dependent unselective deglycosylation of
      both CSs and DSs was performed, we used chondroitin 4-O-sulfotransferase-1
      (Chst11/C4st1)- and dermatan 4-O-sulfotransferase-1 (Chst14/D4st1)-deficient NSCs
      specific for CSs and DSs, respectively, to investigate the involvement of
      specific sulfation profiles of CS and DS chains, and thus the potentially
      distinct roles of CSs and DSs in NSC biology. In comparison to wild-type
      controls, deficiency for Chst14 resulted in decreased neurogenesis and diminished
      proliferation of NSCs accompanied by increased expression of GLAST and decreased
      expression of Mash-1, and an upregulation of the expression of the receptors for
      fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF). By
      contrast, deficiency in Chst11 did not influence NSC proliferation, migration or
      differentiation. These observations indicate for the first time that CSs and DSs
      play distinct roles in the self-renewal and differentiation of NSCs.

PMID- 22159419
TI  - ARL4A acts with GCC185 to modulate Golgi complex organization.
AB  - ADP-ribosylation factor-like protein 4A (ARL4A) is a developmentally regulated
      member of the ARF/ARL GTPase family. The primary structure of ARL4A is very
      similar to that of other ARF/ARL molecules, but its function remains unclear. The
      trans-Golgi network golgin GCC185 is required for maintenance of Golgi structure
      and distinct endosome-to-Golgi transport. We show here that GCC185 acts as a new
      effector for ARL4 to modulate Golgi organization. ARL4A directly interacts with
      GCC185 in a GTP-dependent manner. Sub-coiled-coil regions of the CC2 domain of
      GCC185 are required for the interaction between GCC185 and ARL4A. Depletion of
      ARL4A reproduces the GCC185-depleted phenotype, causing fragmentation of the
      Golgi compartment and defects in endosome-to-Golgi transport. GCC185 and ARL4A
      localize to the Golgi independently of each other. Deletion of the ARL4A
      interacting region of GCC185 results in inability to maintain Golgi structure.
      Depletion of ARL4A impairs the interaction between GCC185 and cytoplasmic linker
      associated proteins 1 and 2 (CLASP1 and CLASP2, hereafter CLASPs) in vivo, and
      abolishes the GCC185-mediated Golgi recruitment of these CLASPs, which is crucial
      for the maintenance of Golgi structure. In summary, we suggest that ARL4A alters
      the integrity of the Golgi structure by facilitating the interaction of GCC185
      with CLASPs.

PMID- 22159418
TI  - Cell organization, growth, and neural and cardiac development require alphaII
      spectrin.
AB  - Spectrin alpha2 (alphaII-spectrin) is a scaffolding protein encoded by the Spna2
      gene and constitutively expressed in most tissues. Exon trapping of Spna2 in
      C57BL/6 mice allowed targeted disruption of alphaII-spectrin. Heterozygous
      animals displayed no phenotype by 2 years of age. Homozygous deletion of Spna2
      was embryonic lethal at embryonic day 12.5 to 16.5 with retarded intrauterine
      growth, and craniofacial, neural tube and cardiac anomalies. The loss of alphaII
      spectrin did not alter the levels of alphaI- or betaI-spectrin, or the
      transcriptional levels of any beta-spectrin or any ankyrin, but secondarily
      reduced by about 80% the steady state protein levels of betaII- and betaIII
      spectrin. Residual betaII- and betaIII-spectrin and ankyrins B and G were
      concentrated at the apical membrane of bronchial and renal epithelial cells,
      without impacting cell morphology. Neuroepithelial cells in the developing brain
      were more concentrated and more proliferative in the ventricular zone than
      normal; axon formation was also impaired. Embryonic fibroblasts cultured on
      fibronectin from E14.5 (Spna2(-/-)) animals displayed impaired growth and
      spreading, a spiky morphology, and sparse lamellipodia without cortical actin.
      These data indicate that the spectrin-ankyrin scaffold is crucial in vertebrates
      for cell spreading, tissue patterning and organ development, particularly in the
      developing brain and heart, but is not required for cell viability.

PMID- 22159420
TI  - Collagen V is a dominant regulator of collagen fibrillogenesis: dysfunctional
      regulation of structure and function in a corneal-stroma-specific Col5a1-null
      mouse model.
AB  - Collagen V is a regulatory fibril-forming collagen that forms heterotypic fibrils
      with collagen I. Deletion of collagen V in the mouse is associated with a lack of
      fibril assembly in the embryonic mesenchyme, with a resultant lethal phenotype.
      The current work elucidates the regulatory roles of collagen V during development
      and growth of tissues. A conditional mouse model with a mutation in Col5a1 was
      developed using a Cre-loxP approach. Col5a1 was ablated in Col5a1(flox/flox) mice
      using a cornea stroma-specific Kera-Cre driver mouse to produce a bitransgenic
      Col5a1(Deltast/Deltast) line that is null for collagen V. This permits analyses
      of the corneal stroma, a widely used model for studies of collagen V. The
      collagen-V-knockout stroma demonstrated severe dysfunctional regulation of
      fibrillogenesis. Fibril diameters were significantly increased, with an abnormal,
      heterogeneous distribution; fibril structure was abnormal, fibril number was
      decreased and lamellae were disorganized with decreased stroma thickness. The
      phenotype was more severe in the anterior versus posterior stroma. Opacity was
      demonstrated throughout the Col5a1(Deltast/Deltast) stroma, with significantly
      increased haze intensity compared with control mice. These data indicate central
      regulatory roles for collagen V in fibril and matrix assembly during tissue
      development, with dysfunctional regulation resulting in a functional loss of
      transparency.

PMID- 22159422
TI  - CCAAT enhancer-binding proteins have long boney fingers.

PMID- 22159421
TI  - WRN helicase regulates the ATR-CHK1-induced S-phase checkpoint pathway in
      response to topoisomerase-I-DNA covalent complexes.
AB  - Checkpoints are cellular surveillance and signaling pathways that coordinate the
      response to DNA damage and replicative stress. Consequently, failure of cellular
      checkpoints increases susceptibility to DNA damage and can lead to profound
      genome instability. This study examines the role of a human RECQ helicase, WRN,
      in checkpoint activation in response to DNA damage. Mutations in WRN lead to
      genomic instability and the premature aging condition Werner syndrome. Here, the
      role of WRN in a DNA-damage-induced checkpoint was analyzed in U-2 OS (WRN wild
      type) and isogenic cells stably expressing WRN-targeted shRNA (WRN knockdown).
      The results of our studies suggest that WRN has a crucial role in inducing an S
      phase checkpoint in cells exposed to the topoisomerase I inhibitor campthothecin
      (CPT), but not in cells exposed to hydroxyurea. Intriguingly, WRN decreases the
      rate of replication fork elongation, increases the accumulation of ssDNA and
      stimulates phosphorylation of CHK1, which releases CHK1 from chromatin in CPT
      treated cells. Importantly, knockdown of WRN expression abolished or delayed all
      these processes in response to CPT. Together, our results strongly suggest an
      essential regulatory role for WRN in controlling the ATR-CHK1-mediated S-phase
      checkpoint in CPT-treated cells.

PMID- 22159423
TI  - Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines:
      clinical implications.
AB  - Although colorectal cancer can be successfully treated by conventional strategies
      such as chemo/radiotherapy and surgery, a substantial number of cases, in
      particular those with liver metastases, remain incurable. Therefore, novel
      treatment approaches are warranted. The IGF-1R and its ligands, mainly IGF-1 and
      IGF-2, have been suggested to play pivotal roles in proliferation, survival and
      migration of adenocarcinoma cells of the colon/rectum. Therefore, interference
      with IGF-1R-mediated signaling may represent a therapeutic option for this
      malignancy. In this study, semi-quantitative RT-PCR analyses of 48 paired,
      colorectal cancer patient samples showed significant overexpression of tumor IGF
      1R and IGF-2 mRNA. There was also an overexpression of MMP-7, which was
      significantly correlated with histopathological parameters. Based on these
      findings, the effect of the IGF-1R-inhibitory cyclolignan picropodophyllin (PPP)
      was assessed in the four colon carcinoma cell lines HT-29, HCT-116, DLD-1 and
      CaCO-2. PPP strongly and dose-dependently inhibited proliferation and migration
      in all cell lines. However, when exposed to 0.5 uM PPP, only HT-29 showed a net
      decrease of viable cells as compared with the cell number at the beginning of the
      experiment, a finding that coincided with decreased expression/phosphorylation of
      IGF-1R, AKT and ERK. This cell line also exhibited PPP-induced downregulation of
      MMP-7 and MMP-9. Similar to the DLD-1 and HCT-116 cell lines, HT-29 also showed
      substantial cell detachment in response to PPP. Although a net reduction of cells
      by PPP seems to require a synchronized downregulation of IGF-1R, AKT and ERK1/2,
      part of the antitumor effect may be explained by other, possibly IGF-1R-unrelated
      mechanism(s). Such a multitude of inhibitory effects of PPP in colon cancer cells
      together with its low toxicity in vivo makes it a promising drug candidate in the
      treatment of this disease.

PMID- 22159424
TI  - Recombinant antibodies and their use in biosensors.
AB  - Inexpensive, noninvasive immunoassays can be used to quickly detect disease in
      humans. Immunoassay sensitivity and specificity are decidedly dependent upon high
      affinity, antigen-specific antibodies. Antibodies are produced biologically. As
      such, antibody quality and suitability for use in immunoassays cannot be readily
      determined or controlled by human intervention. However, the process through
      which high-quality antibodies can be obtained has been shortened and streamlined
      by use of genetic engineering and recombinant antibody techniques. Antibodies
      that traditionally take several months or more to produce when animals are used
      can now be developed in a few weeks as recombinant antibodies produced in
      bacteria, yeast, or other cell types. Typically most immunoassays use two or more
      antibodies or antibody fragments to detect antigens that are indicators of
      disease. However, a label-free biosensor, for example, a quartz-crystal
      microbalance (QCM) needs one antibody only. As such, the cost and time needed to
      design and develop an immunoassay can be substantially reduced if recombinant
      antibodies and biosensors are used rather than traditional antibody and assay
      (e.g. enzyme-linked immunosorbant assay, ELISA) methods. Unlike traditional
      antibodies, recombinant antibodies can be genetically engineered to self-assemble
      on biosensor surfaces, at high density, and correctly oriented to enhance antigen
      binding activity and to increase assay sensitivity, specificity, and stability.
      Additionally, biosensor surface chemistry and physical and electronic properties
      can be modified to further increase immunoassay performance above and beyond that
      obtained by use of traditional methods. This review describes some of the
      techniques investigators have used to develop highly specific and sensitive,
      recombinant antibody-based biosensors for detection of antigens in simple or
      complex biological samples.

PMID- 22159426
TI  - Assessing temporal representativeness of water quality monitoring data.
AB  - The effectiveness of different monitoring methods in detecting temporal changes
      in water quality depends on the achievable sampling intervals, and how these
      relate to the extent of temporal variation. However, water quality sampling
      frequencies are rarely adjusted to the actual variation of the monitoring area.
      Manual sampling, for example, is often limited by the level of funding and not by
      the optimal timing to take samples. Restrictions in monitoring methods therefore
      often determine their ability to estimate the true mean and variance values for a
      certain time period or season. Consequently, we estimated how different sampling
      intervals determine the mean and standard deviation in a specific monitoring area
      by using high frequency data from in situ automated monitoring stations. Raw
      fluorescence measurements of chlorophyll a for three automated monitoring
      stations were calibrated by using phycocyanin fluorescence measurements and
      chlorophyll a analyzed from manual water samples in a laboratory. A moving block
      bootstrap simulation was then used to estimate the standard errors of the mean
      and standard deviations for different sample sizes. Our results showed that in a
      temperate, meso-eutrophic lake, relatively high errors in seasonal statistics can
      be expected from monthly sampling. Moreover, weekly sampling yielded relatively
      small accuracy benefits compared to a fortnightly sampling. The presented method
      for temporal representation analysis can be used as a tool in sampling design by
      adjusting the sampling interval to suit the actual temporal variation in the
      monitoring area, in addition to being used for estimating the usefulness of
      previously collected data.

PMID- 22159425
TI  - Identification of oligosaccharides from histopathological sections by MALDI
      imaging mass spectrometry.
AB  - Direct tissue analysis using matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometry (MS) provides the means for in situ molecular analysis of a
      wide variety of biomolecules. This technology--known as imaging mass spectrometry
      (IMS)--allows the measurement of biomolecules in their native biological
      environments without the need for target-specific reagents such as antibodies. In
      this study, we applied the IMS technique to formalin-fixed paraffin-embedded
      samples to identify a substance(s) responsible for the intestinal obstruction
      caused by an unidentified foreign body. In advance of IMS analysis, some
      pretreatments were applied. After the deparaffinization of sections, samples were
      subjected to enzyme digestion. The sections co-crystallized with matrix were
      desorbed and ionized by a laser pulse with scanning. A combination of alpha
      amylase digestion and the 2,5-dihydroxybenzoic acid matrix gave the best mass
      spectrum. With the IMS Convolution software which we developed, we could
      automatically extract meaningful signals from the IMS datasets. The
      representative peak values were m/z 1,013, 1,175, 1,337, 1,499, 1,661, 1,823, and
      1,985. Thus, it was revealed that the material was polymer with a 162-Da unit
      size, calculated from the even intervals. In comparison with the mass spectra of
      the histopathological specimen and authentic materials, the main component
      coincided with amylopectin rather than amylose. Tandem MS analysis proved that
      the main components were oligosaccharides. Finally, we confirmed the
      identification of amylopectin by staining with periodic acid-Schiff and iodine.
      These results for the first time show the advantages of MALDI-IMS in combination
      with enzyme digestion for the direct analysis of oligosaccharides as a major
      component of histopathological samples.

PMID- 22159427
TI  - Outcome of biventricular repair in infants with multiple left heart obstructive
      lesions.
AB  - The decision to perform biventricular repair for infants with multiple
      obstructive or hypoplastic left heart lesions (LHL) and borderline left ventricle
      (LV) may be controversial. This study sought to assess the mortality and
      morbidity of patients with LHL after biventricular repair and to determine the
      growth of the left-sided cardiac structures. Retrospective analysis of 39
      consecutive infants with LHL who underwent biventricular repair was performed.
      The median age at surgery was 7 days (range 1-225 days), and the median follow-up
      period was 34 months (range 1-177 months). Between diagnosis and the end of the
      follow-up period, the size of the aortic annulus (z-score -4.1 +/- 2.8 vs. -0.1
      +/- 2.7) and the LV (LV end-diastolic diameter z-score -1.7 +/- 2.8 vs. 0.21 +/-
      1.7) normalized. During the follow-up period, 23 patients required 39
      reinterventions (62%) consisting of redo surgery for 21 patients (57%) and
      catheter-guided reinterventions for 8 patients (22%). At the end of the follow-up
      period, 25 of 34 patients were doing subjectively well; 10 children (29%)
      received cardiac medication; 12 (35%) presented with failure to thrive (weight <=
      P3) and 5 (15%) with pulmonary hypertension. The overall mortality rate was 13%.
      Biventricular repair for patients with multiple LHL results in sufficient growth
      of the left-sided cardiac structures. Nevertheless, residual or newly developing
      obstructive lesions and pulmonary hypertension are frequent, causing significant
      morbidity that requires reintervention.

PMID- 22159428
TI  - The relevance of P2Y(12)-receptor gene variation for the outcome of clopidogrel
      treated patients undergoing elective coronary stent implantation: a clinical
      follow-up.

PMID- 22159429
TI  - Mechanistic aspects of molecular formation and crystallization of zinc oxide
      nanoparticles in benzyl alcohol.
AB  - Zinc oxide nanostructures are known to exist in a great variety of morphologies.
      However, the underlying mechanisms leading to these architectures are far from
      being fully understood. Here, we present a time dependent study of the generation
      of zinc oxide nanorods, which arrange into bundles with a fan- or bouquet-like
      structure, using the benzyl alcohol route. The structural evolution of the
      nanoparticles was monitored by electron microscopy techniques, whereas the
      progress of the chemical reaction was followed by quantification of the organic
      by-products using gas chromatography. With this study we give a detailed insight
      into the formation of the zinc oxide structures, which involves a complex pathway
      based on many in parallel occurring processes such as crystallization of primary
      particles, their oriented attachment and surface reconstruction inside the
      nanoparticulate agglomerates. However, in spite of such an intricate growth
      behavior, the ZnO nanostructures are surprisingly uniform in size and shape.

PMID- 22159430
TI  - The high yielding synthesis of pillar[5]arenes under Friedel-Crafts conditions
      explained by dynamic covalent bond formation.
AB  - Systematic investigations of the cyclooligomerization of 1,4-disubstituted
      hydroquinone derivatives under Friedel-Crafts conditions have been carried out to
      demonstrate that the formation of pillar[5]arenes occurs under thermodynamic
      control.

PMID- 22159431
TI  - Effect of zafirlukast on capsular contracture around silicone implants in rats.
AB  - PURPOSE: To evaluate the effect of zafirlukast on capsular contracture around
      silicone implants by measuring the pressure within the implant, using a rat
      experimental model. METHODS: Forty adult female Wistar rats were used. Each one
      received two silicone implants, one with smooth-surface and the other with
      textured-surface. They were randomly divided into four groups (n=10). The rats of
      control group I were sacrificed after the implants. The remaining animals were
      subjected to a daily regimen of intra-peritoneal injection for a period of 90
      days and they were distributed as follows: control group II received 0.9%
      physiological saline solution; experimental group I received zafirlukast 1.25
      mg/kg; and experimental group II received zafirlukast 5 mg/kg. The measurement of
      intra-implant pressure of control group I was determined on the surgery day and
      in other groups on the ninetieth day, after being sacrificed. RESULTS: In the
      evaluation of textured implants there was an increase of internal pressure in the
      control group II, and there was no increase in the experimental groups. Compared
      to the controls there were not significant differences in smooth implants.
      CONCLUSION: Zafirlukast reduced the risk of developing capsular contracture
      around silicone implants with textured surface.

PMID- 22159432
TI  - The effect of maternal hypercholesterolemia on the placenta and fetal arteries in
      rabbits.
AB  - PURPOSE: To investigate the degree of placental permeability in dyslipidemic
      rabbits and the consequent vascular dysfunction in fetuses of female rabbits with
      high lipoprotein levels. METHODS: Fifteen adult females New Zealand White rabbits
      were divided into two groups. Group 1(n=5) - hypercholesterolemic diet with 0.5%
      cholesterol, and Group 2 (n=10) - control. On day 30, the levels of plasma
      lipoproteins and triglycerides were analyzed in the mothers, and the presence of
      collagen was analyzed in the placenta as well as in fetal coronary and aorta.
      Statistical analyses used the Student's t and the Mann-Whitney tests. RESULTS:
      Lipoprotein levels were significantly different (p=0.02 to p<0.001) in
      experimental and control groups. In the hypercholesterolemic group, total
      cholesterol levels were in average 793 mg/dl; triglycerides were in average 257
      mg/dl; HDL-C was 48 mg/dl, and LDL-C was in average 692 mg/dl. The amount of
      collagen per micrometers square (mu2) in samples from hypercholesterolemic
      animals was significantly higher than in the control group. CONCLUSIONS: The
      study confirmed placental permeability to lipoproteins, shown by increased
      amounts of collagen in fetal tissues. This alteration results in increased
      susceptibility to atherosclerosis in adult life, representing a risk factor for
      the early development of disease, which may appear even in the prenatal period.

PMID- 22159433
TI  - [Experimental model of ultrasound thermotherapy in rats inoculated with Walker
      236 tumor].
AB  - PURPOSE: To develop a model to evaluate the effects of focal pulsed ultrasound
      (US) waves as a source of heat for treatment of murine subcutaneous implanted
      Walker tumor. METHODS: An experimental, controlled, comparative study was
      conducted. Twenty male Wistar rats (160-300 g) randomized in 2 equal groups (G-1:
      Control and G-2: Hyperthermia) were inoculated with Walker-256 carcinosarcoma
      tumor. After 5 days G-2 rats were submitted to 45oC hyperthermia. Heat was
      delivered directly to the tumor by an ultrasound (US) equipment (3 MHz frequency,
      1,5W/cm3). Tumor temperature reached 45o C in 3 minutes and was maintained at
      this level for 5 minutes. Tumor volume was measured on days 5, 8, 11, 14 e 17
      post inoculation in both groups. Unpaired t-test was used for comparison. P<0.05
      was considered significant. RESULTS: Tumor volume was significantly greater in
      day 5 and decreased in days 11, 14 and 17 in treated rats. Rats treated with
      hyperthermia survived longer than control animals. On the 29th day following
      tumor inoculation, 40% of control rats and 77.78% of hyperthermia-treated rats
      remained alive. CONCLUSION: The proposed model is quite simple and may be used in
      less sophisticated laboratory settings for studying the effects of focal
      hyperthermia in the treatment of malignant implanted tumours or in survival
      studies.

PMID- 22159434
TI  - Experimental model of smoking and simulation of reflux with acid and pepsin in
      rats.
AB  - PURPOSE: To develop experimental models to evaluate the effects of hydrochloric
      acid associated with the pepsin instilled in the mucosa of the upper esophagus
      and the esophagogastric junction of young male rats Wistar, simulating injury
      caused by gastroesophageal reflux on the mucosa of aero-digestive tract in humans
      as well as the action of the risk exposure of mucosa to cigarette smoke. METHODS:
      Fifty young male Wistar rats divided in 5 groups with 10 animals each one,
      respectively simulating pharyngo-laryngeal reflux and gastroesophageal reflux,
      pharyngo-laryngeal reflux and smoking, smoking only, gastroesophageal reflux and
      control group. RESULTS: The histopathologic studies no recorded neoplasias, only
      mild changes and no significant alterations. The hemo-oximetry (carboxyhemoglobin
      and methemoglobim) and CO2 concentration confirm that the animals were submitted
      to high intensity of exposure to carcinogens in tobacco and its derivatives.
      CONCLUSION: The experimental models were highly efficient, practical, easy to use
      and economical and can be employed in other similar studies to determine the
      harmful effects by smoking and reflux.

PMID- 22159435
TI  - The effect of progesterone in the prevention of the chemically induced
      experimental colitis in rats.
AB  - PURPOSE: To study the effects of progesterone on an experimental colitis model.
      METHODS: Wistar albino rats were treated subcutaneously with 2mg/kg once a day
      during seven days Colitis was induced by intrarectal administration of 5mg
      trinitrobenzene sulfonic acid (TNBS). Disease activities, macroscopic and
      microscopic scores were evaluated. To determine the response provoked by
      progesterone we measured Colonic malondialdehyde (MDA), TNF alfa, IL-6 and Nitric
      oxide (NO) levels in addition to the MPO (Myeloperoxidase) and caspase-3
      activities. RESULTS: Progesterone ameliorated significantly the macroscopic and
      microscopic scores. TNBS-induced colitis significantly increased the colonic MDA
      levels and caspase-3 activities in group 2 in comparison to the control group.
      The results of the study revealed a decline in MDA, NO, IL6 and TNF-alpha levels
      in the colon tissue and in blood due to progesterone therapy in group 3 when
      compared to the group 2, a significant improvement. Progesterone treatment was
      associated with decreased MDA, MPO, TNF alfa and caspase-3 activity. CONCLUSION:
      Progesterone therapy decreased oxidative damage in the colonic mucosa.

PMID- 22159436
TI  - Effect of a hyperlipidic diet rich in omegas 3, 6 and 9 on aberrant crypt
      formation in rat colonic mucosa.
AB  - PURPOSE: To determine whether a hypercaloric and hyperlipidic diet enriched with
      polyunsaturated fatty acids influences the formation of aberrant crypt foci (ACF)
      in colonic mucosa of Wistar rats treated with azoxymethane (AOM). METHODS: At
      eight weeks of life, the rats were assigned to four groups: Group I-standard diet
      (STD) not treated with AOM; Group II-hypercaloric and hyperlipidic diet (FED),
      not treated with AOM; Group III-STD, treated with AOM; Group IV-FED, treated with
      AOM. At 16 weeks, the animals were injected intraperitoneal with 0.9% saline
      solution (Group I and II) or AOM at 15 mg/Kg (Groups III and IV) once a week for
      two weeks. Fifteen weeks later, the animals were euthanized. RESULTS: FED
      promoted weight gain in Groups II and IV compared to Groups I and III,
      respectively. The groups did not differ with regard to the total number of ACF.
      The Chi-square test revealed no predominance of the presence of foci with <4
      crypts. However, foci with >=5 crypts were proportionally more prevalent in Group
      III than in Group IV (p=0.043). CONCLUSION: The administration of polyunsaturated
      fatty acids did not interfere with the formation of aberrant crypt foci, but
      reduced ACF multiplicity, exercising an attenuating effect on carcinogenesis.

PMID- 22159437
TI  - Renal histology and immunohistochemistry after acute hemorrhage in rats under
      sevoflurane and ketoprofen effect.
AB  - PURPOSE: To investigate the influence of intravenous nonselective cyclooxygenase
      inhibitor, ketoprofen (keto), on kidney histological changes and kidney
      cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1),
      levels after hemorrhage of 30% of volemia (three times 10%, intervals of 10 min)
      in rats. METHODS: Under sevoflurane (sevo) anesthesia, sevo and sevo+keto groups
      (10 rats each) were instrumented for Ringer solution (5 mL/kg/h) administration
      and mean arterial pressure (MAP) evaluation, plus keto (1.5mg/kg) administration
      in sevo+keto group in the beginning of anesthesia. Rectal temperature was
      continuously measured. The baseline data of temperature and MAP were collected at
      the first hemorrhage (T1), the third hemorrhage (T2) and 30 min after T2 (T3).
      Bilateral nephrectomy was achieved for histology and immunohistochemistry.
      RESULTS: In both groups, temperature and MAP diminished from initial values.
      Hypothermia was greater in sevo group (p=0.0002). Tubular necrosis was more
      frequent in sevo group (p=0.02). The studied cytokines were equally present in
      the kidneys of both groups. CONCLUSION: Ketoprofen was more protective to the rat
      kidney in condition of anesthesia with sevoflurane and hypovolemia, but it seems
      that TNF-alpha and IL-1 were not involved in that protection.

PMID- 22159438
TI  - Electroanalgesia for the postoperative control pain in dogs.
AB  - PURPOSE: To evaluate the analgesic and neuroendocrine effects of electroanalgesia
      in dogs undergoing ovariohysterectomy. METHODS: Eighteen dogs were randomly
      distributed to three groups of six animals each and received either electrical
      stimuli at acupuncture points (EA), at peri-incisional dermatomes (DER) and at
      both acupuncture points and peri-incisional dermatomes (EAD). Pre-anesthetic
      medication was acepromazine (0.05mg kg-1, IV). Anesthesia was induced with
      propofol (4 to 5mg kg-1, IV) and maintained with isoflurane. Postoperatively pain
      degree was measured using a numerical rating scale. Dogs were scored at 1, 3, 6,
      12 and 24 hours postoperative. If the pain score was >=6, supplemental morphine
      (0.5mg kg-1, IM) was administered. Serum cortisol concentration was measured
      before pre-anesthetic medication (basal), and at 1, 12 and 24 hours
      postoperative. RESULTS: EA and EAD- treated dogs had lower pain scores than DER
      treated dogs one hour postoperatively. Fewer EA and EAD-treated dogs required
      rescue analgesia. Serum cortisol did not differ among treatments. CONCLUSION:
      Preoperative application of electrical stimuli to acupuncture points isolated or
      in combination with peri-incisional dermatomes provides a reduced postoperative
      opioid requirement and promotes an effective analgesia in dogs undergoing
      ovariohysterectomy.

PMID- 22159439
TI  - The role of N-acetyl-cysteine in the lung remote injury after hepatic ischemia
      and reperfusion in rabbits.
AB  - PURPOSE: To study the lesions in the lung of rabbits caused by
      ischemia/reperfusion hepatic (I/R) after the use of N-acetyl-cysteine (NAC).
      METHODS: Twenty-four rabbits distributed in two groups: control group GI (n = 12)
      5% glucose solution and experiment group GII (n = 12) NAC. The animals were pre
      anesthetized with 1% acepromazine maleate and anesthetized with ketamine 10% and
      2% xylazine intramuscularly. The GI and GII were given glucose solution
      intravenously or NAC 15 min before occlusion of the hepatic pedicle (30 min).
      After the period of reperfusion of 24h (n = 6) or 48 h (n = 6), liver and lung
      samples were collected for histology and immunohistochemistry to assess the
      impairment of cell. RESULTS: The animals of GII and GII-24h-48 h showed
      parenchyma liver close to normal, when using NAC. The GII and GII-24h-48 h showed
      lower thickness of alveolar cells that GI and GI-24h-48 h. The expression of
      caspase 3 in lung cells GII presented smaller value compared to the GI group.
      CONCLUSION: N-acetyl-cysteine administered 15 min prior to the injury
      ischemia/reperfusion had a significant protective role by minimizing lung injury
      and apoptotic morphology in the period observed.

PMID- 22159440
TI  - Castor oil polyurethane containing silica nanoparticles as filling material of
      bone defect in rats.
AB  - PURPOSE: To evaluate the biologic behavior of the castor polymer containing
      silica nanoparticles as a bone substitute in diafisary defect. METHODS: Twenty
      seven male Rattus norvegicus albinus Wistar lineage were submitted to bone defect
      filled with castor oil polymer. Three experimental groups had been formed with
      nine animals each: (1) castor oil polymer containing only calcium carbonate; (2)
      castor oil polymer with calcium carbonate and doped with 5% of silica
      nanoparticles; (3) castor polymer with calcium carbonate doped with 10% of silica
      nanoparticles; 3 animals of each group were submitted to euthanasia 15, 30 and 60
      days after experimental procedure, and their femurs were removed to histological
      evaluation. RESULTS: there was bone growth in all the studied groups, with a
      greater tendency of growth in the group 1. After 30 days all the groups presented
      similar results. After 60 days a greater amount of fibroblasts, osteoblasts,
      osteocytes and osteoclasts in group 3 was observed, with integrated activity of 3
      kinds of cells involved in the bone activation-reabsorption-formation.
      CONCLUSIONS: The castor polymer associated to the silica nanoparticles is
      biocompatible and allows osteoconduction. The presence of osteoprogenitors cells
      suggests silica osteoinduction capacity.

PMID- 22159441
TI  - Evaluation of the effects of carbon dioxide pneumoperitoneum on abdominal wall
      wound healing in rats undergoing segmental resection and anastomosis of the left
      colon.
AB  - PURPOSE: To evaluate the influence of carbon dioxide pneumoperitoneum on
      abdominal wall wound healing in rats. METHODS: Eighty rats underwent laparotomy,
      segmental left colon resection, and anastomosis. The animals were divided into
      three experimental groups and one control group: EI = pneumoperitoneum for 30
      minutes before laparotomy (n=20); EII = pneumoperitoneum for 30 minutes after
      abdominal closure (n=20); EIII = pneumoperitoneum for 30 minutes before
      laparotomy and 30 minutes after abdominal closure (n=20); C = control group,
      without pneumoperitoneum (n=20). In each group, 10 animals were killed 7 days and
      10 animals 14 days postoperatively. A segment of the abdominal wall was resected
      and subjected to tensile strength testing. Another segment of abdominal muscle
      was used for histopathological analysis; the specimens were fixed in formalin and
      stained with hematoxylin and eosin. RESULTS: There were no differences in
      histopathology and tensile strength values among animals in the experimental and
      control groups 7 or 14 days after surgery. CONCLUSION: Under the present
      experimental conditions, carbon dioxide pneumoperitoneum did not interfere with
      abdominal wall wound healing.

PMID- 22159442
TI  - Proliferative effect of aqueous extract of Hyptis fructicosa on liver
      regeneration after partial hepatectomy in rats.
AB  - PURPOSE: To evaluate the effect of aqueous extract of Hyptis fructicosa on
      hepatic regeneration after partial hepatectomy in rats. METHODS: Sixteen rats
      were divided in two groups: C (Control Group) and HF (Whose rats received aqueous
      extract of Hyptis fructicosa during 4 days using the dose of 100 mg/kg/day). On
      the consecutive day of this treatment, the animals of both groups underwent
      hepatectomy of about 67% of liver. Twenty four hours later, they were sacrificed,
      and the remaining mass of liver was removed and prepared to be studied through
      the PCNA immunohistochemical technique. RESULTS: The liver regeneration index of
      HF group was 53.56 +/- 18.91%, while in C group was 21.12 +/- 8.29% (p=0.0003).
      CONCLUSION: These results show that the administration of aqueous extract of
      Hyptis fructicosa using the dose of 100mg/kg/day increased the hepatocyte
      proliferation in the group HF.

PMID- 22159443
TI  - New kidney immobilization method for percutaneous renal biopsy technique in cats.
      Operational aspects and complications.
AB  - PURPOSE: Evaluate a new immobilization kidney method for collecting blind
      percutaneous renal biopsies (RB) in healthy cats. METHODS: Ten cats were biopsied
      by a modified blinded percutaneous technique using semi-automated needles. Were
      evaluated the operational aspects of the technique, its complications, and the
      quality of the obtained samples. The evaluation included physical examination,
      hemogram, urinalysis, abdominal ultrasound, renal function, and histopathology of
      the biopsy specimens. RESULTS: The developed technique was fast and easy to
      perform; it required two operators, and the right kidney was elected for specimen
      collection. After the RB, a decrease in hematocrit levels was observed in
      addition to hematuria and perirenal transient hematoma; however, no clinical
      consequences were observed, and normal parameters were restored within 48 hrs.
      There were no major complications or deaths, alterations in the physical
      examination or renal function, or signs of infection. Of the samples, 95%
      revealed the presence of renal tissue, and in 100% of the cats the samples were
      of diagnostic quality. CONCLUSION: The technique was easily performed, provided
      adequate material for diagnosis with minimal transient complications.

PMID- 22159444
TI  - Filling of extraction sockets with autogenous bone in cats.
AB  - PURPOSE: To evaluate bone healing in the extraction socket of the feline
      mandibular canine tooth after grafting. METHODS: Eighteen adult cats were
      submitted to unilateral extraction of mandibular canine tooth and divided into
      three groups. In group 1 (n=6), control, the extraction socket was left empty. In
      group 2 (n=6), the extraction socket was filled with autogenous cancellous bone
      from the iliac crest and in group 3 (n=6), with cortical bone chips from the
      iliac crest. Cats were euthanized at 6 weeks postoperative. RESULTS: Immediate
      postoperative radiographs in dorsoventral view showed a radiolucent area at the
      extraction wound. A decreased radiolucency was observed on the radiographs taken
      at 6 weeks postoperative. Histological examination showed formation of woven bone
      within the extraction socket. The percentage of newly formed bone within the
      extraction socket, measured by the histometry, showed no statistically
      significant difference among the values of the three groups (Kruskal-Wallis'test
      p>0.05) (group 1: 52.54 +/- 15.46, group 2: 50.51 +/- 5.01, group 3: 51.85 +/-
      9.52). CONCLUSION: The bone regeneration observed in the extraction sockets
      filled with autogenous cancellous bone or autogenous cortical bone chips was
      similar to that observed in the control sites, given an observation period of 6
      weeks after extraction of the mandibular canine tooth.

PMID- 22159445
TI  - Organic bench model to complement the teaching and learning on basic surgical
      skills.
AB  - PURPOSE: To propose an organic bench model made with fruits/vegetables as an
      alternative to complement the arsenal of simulators used in the teaching and
      learning of basic surgical skills during medical graduation and education.
      METHODS: They were described the training strategies, through the use of fruits
      (or vegetables) to the learning of different techniques of incision, sutures,
      biopsies and basic principles of reconstruction. The preparation of bench model,
      the processes of skill acquisition, feedback and evaluation were also delineated.
      RESULTS: A proposal for teaching based on an organic model with training
      delivered in multiple sessions, with increasing levels of difficulty, and with
      feedback and evaluation during all the process was structured. CONCLUSION: The
      organic model, being simple, versatile, portable, reproducible, readily
      available, and having low cost, is another option to complement the existing
      simulators for teaching and learning of basic surgical skills.

PMID- 22159446
TI  - A catalytic version of hypervalent aryl-lambda3-iodane-induced Hofmann
      rearrangement of primary carboxamides: iodobenzene as an organocatalyst and m
      chloroperbenzoic acid as a terminal oxidant.
AB  - The first catalytic version of hypervalent aryl-lambda(3)-iodane-induced Hofmann
      rearrangement of primary carboxamides, which probably involves in situ generation
      of a tetracoordinated bis(aqua)(hydroxy)phenyl-lambda(3)-iodane complex as an
      active oxidant from a catalytic amount of iodobenzene by the reaction with m
      chloroperbenzoic acid in the presence of HBF(4) in dichloromethane-water under
      mild conditions, was developed.

PMID- 22159447
TI  - Matrine inhibits proliferation and induces apoptosis of the androgen-independent
      prostate cancer cell line PC-3.
AB  - Current strategies to treat androgen-independent prostate cancer are associated
      with a number of challenges and are not yet curative. Matrine is a naturally
      occurring alkaloid extracted from the Chinese herb Sophora flavescens. Matrine
      has shown anti-proliferative properties in a number of types of cancer, including
      breast, gastric, lung and pancreatic tumors. Matrine was also found to promote
      apoptosis and inhibit invasion of cancer cells. We evaluated the antitumor
      effects of matrine on androgen-independent PC-3 prostate cancer cells. The
      effects of matrine on cell cycle progression and apoptosis of PC-3 cells were
      tested. Matrine-treated PC-3 cells underwent G0/G1 cell cycle arrest. There was a
      significant reduction in the number of S phase and G2/M phase cells in the
      treated group when compared to untreated cells. Flow cytometry, as well as
      Annexin-V/PI staining, showed a significant, dose-dependent increase in the
      number of early, as well as late, stage apoptotic cells in matrine-treated cells
      compared to untreated cells. There was also an increase in the number of necrotic
      cells in the matrine-treated group when compared to untreated cells. Matrine
      treatment resulted in increased levels of caspase-3 and Bax and decreased levels
      of Bcl-2. Our data suggest that matrine inhibits the proliferation of androgen
      independent prostate cancer cells by causing G0/G1 cell cycle arrest and
      promoting apoptosis. Matrine-induced apoptosis was mediated by downregulation of
      Bcl-2/Bax ratios and upregulation of caspase-3 levels. Based on our data, we
      suggest that matrine may be a novel addition to the current arsenal of strategies
      used to treat androgen-independent prostate cancer.

PMID- 22159449
TI  - IR laser photodeposition of a-Fe/Si films developing nanograins of ferrisilicate,
      iron disilicide and rare hexagonal iron upon annealing.
AB  - IR laser-induced gas-phase photolysis of Fe(CO)(5)-SiH(4) mixtures occurs as
      SiH(4)-photosensitized decomposition of Fe(CO)(5) is accelerated by products of
      this decomposition and it results in deposition of amorphous Si/Fe nanocomposite
      films. Analyses of the deposited and subsequently annealed solid films were made
      by FTIR, Raman and X-ray photoelectron spectroscopy, X-ray diffraction and
      electron microscopy. The deposited films are amorphous, contain crystalline
      nanostructures of iron silicide FeSi(2) and undergo atmospheric oxidation in
      topmost layers to iron oxide and hydrogenated silicon oxide. Upon annealing they
      develop nanocrystalline structures of ferrisilicate, Fe(1.6)SiO(4), carbon
      encaged iron disilicide, FeSi(2), and very rare hexagonal (high-pressure) Fe
      surviving at ambient conditions. The mechanism of formation of these
      nanostructures is discussed in terms of gas-phase and solid-phase reactions.

PMID- 22159450
TI  - Comparative effects of histone deacetylase inhibitors on p53 target gene
      expression, cell cycle and apoptosis in MCF-7 breast cancer cells.
AB  - Histone deacetylase inhibitors are currently being evaluated for their
      therapeutic potential and have shown considerable promise as adjuvant therapies
      for a number of cancers. This study compared the effects of 2 hydroxamic acid
      based inhibitors, CG-1521 and SAHA, on gene expression, cell cycle and cell death
      in MCF-7 human breast cancer cells. Both compounds show a dose- and time
      dependent effect on cell number (evaluated using crystal violet), however CG-1521
      exerts its effects significantly earlier than SAHA, and CG-1521 induces apoptosis
      (assessed by Apo-BrdU staining and flow cytometry) more rapidly than SAHA. qPCR
      of cell cycle regulatory and apoptotic genes shows that CG-1521 and SAHA modulate
      similar cohorts of p53-responsive genes, however, the levels of induction and the
      timing of the induction differs significantly between the 2 inhibitors. In
      particular SAHA downregulates cell cycle-associated genes that modulate the G1/S
      transition (including cyclin D1 and cdc25a) and the G2/M transition [cyclin B1,
      Plk1, Stk6 (serine-threonine kinase 6, Aurora kinase A) and Kntc2] more
      significantly than CG-1521. In contrast, CG-1521 significantly induces the
      expression of several p53 target genes associated with apoptosis including
      Bnip3/Bnip3L, p21/p21B and Gdf15. The differential levels of gene induction
      provide molecular evidence of both cell cycle arrest and apoptosis, and suggest a
      molecular mechanism that explains the difference in the biological effects of the
      2 histone deacetylase inhibitors.

PMID- 22159451
TI  - Circulating microRNAs: novel biomarkers for cardiovascular diseases.
AB  - MicroRNAs (miRNAs) are a novel class of small, non-coding, single-stranded RNAs
      that negatively regulate gene expression via translational inhibition or mRNA
      degradation followed by protein synthesis repression. Many miRNAs are expressed
      in a tissue- and/or cell-specific manner and their expression patterns are
      reflective of underlying patho-physiologic processes. miRNAs can be detected in
      serum or in plasma in a remarkably stable form, making them attractive biomarkers
      for human diseases. This review describes the progress of identifying circulating
      miRNAs as novel biomarkers for diverse cardiovascular diseases, including acute
      myocardial infarction, heart failure, coronary artery disease, diabetes, stroke,
      essential hypertension, and acute pulmonary embolism. In addition, the origin and
      function and the different strategies to identify circulating miRNAs as novel
      biomarkers for cardiovascular diseases are also discussed. Rarely has an
      opportunity arisen to advance such new biology for the diagnosis of cardiac
      diseases.

PMID- 22159452
TI  - Intravenous and intradermal TriMix-dendritic cell therapy results in a broad T
      cell response and durable tumor response in a chemorefractory stage IV-M1c
      melanoma patient.
AB  - Dendritic cells (DCs) electroporated with mRNA encoding CD70, CD40L and a
      constitutively active toll-like receptor 4 (TriMix-DC) have an increased T-cell
      stimulatory capacity. In a prospective phase IB clinical trial, we treated
      melanoma patients with intradermal and intravenous injections of autologous
      TriMix-DC co-electroporated with mRNA encoding full-length MAGE-A3, MAGE-C2,
      tyrosinase and gp100. We report here the immunological and clinical results
      obtained in one patient with a particularly favorable outcome. This patient had
      stage IV-M1c melanoma with documented progression during dacarbazine chemotherapy
      and received 5 TriMix-DC injections. Following DC therapy, a broad CD8(+) T-cell
      response against multiple epitopes derived from all four treatment antigens was
      found in the blood and among T cells derived from DTH biopsy. In addition, CD4(+)
      T cells recognizing different MAGE-A3-derived epitopes were detected in DTH
      derived cells. A spontaneous anti-MAGE-C2 CD8(+) T-cell response was present
      prior to TriMix-DC therapy and increased during treatment. The tumor response was
      assessed with 18-fluorodeoxyglucose-positron emission/computed tomography. We
      documented a partial tumor response according to RECIST criteria with a marked
      reduction in (18)F-FDG-uptake by lung, lymph node and bone metastases. The
      patient remains free from progression after 12 months of follow-up. This case
      report indicates that administration of autologous TriMix-DC by the combined
      intradermal and intravenous route can mediate a durable objective tumor response
      accompanied by a broad T-cell response in a chemorefractory stage IV-M1c melanoma
      patient.

PMID- 22159453
TI  - Hemicryptophane host as efficient primary alkylammonium ion receptor.
AB  - Hemicryptophane 3 was found to be an efficient and selective primary
      alkylammonium receptor. Binding constants are 1000-fold higher than those
      previously reported for hemicryptophane hosts. Efficient complexation of dopamine
      emphasizes the use of this host for neurotransmitter complexation. Density
      functional theory calculations were performed and highlight host-guest
      complementarities.

PMID- 22159455
TI  - 2,3-unsubstituted chromones and their enaminone precursors as versatile reagents
      for the synthesis of fused pyridines.
AB  - A divergent and regioselective approach to fused pyridines was developed through
      formal [3 + 3] cyclocondensations from simple 2,3-unsubstituted chromones or
      their enaminone precursors.

PMID- 22159456
TI  - Revisiting the molecular epidemiology of factor XI deficiency: nine new mutations
      and an original large 4qTer deletion in western Brittany (France).
AB  - Constitutional deficiency in factor XI (FXI) is a rare bleeding disorder in the
      general population, with the exception of Ashkenazi Jews. During the last decade,
      the detection of FXI-deficient patients has shifted from clinical screening
      identifying mostly severe bleeders to biological screening combining findings of
      prolonged activated partial thromboplastin time and FXI coagulation activity
      (FXI:C) below 50 U/dl. The goal of this study was to determine the molecular
      basis of FXI deficiency in western Brittany, France. Over the course of four
      years, we detected 98 FXI-deficient patients through biological screening, and 44
      patients agreed to participate in this study corresponding to 25 index cases. We
      developed an efficient mutation detection strategy (combining direct sequencing
      and QFM-PCR to search for heterozygous rearrangements in a routine setting) that
      detected  F11  mutations in 24 out of the 25 index cases. An unexpected allelic
      heterogeneity was found, with 14 different single point mutations being detected,
      among which nine are new. Moreover, a large heterozygous deletion of the entire 
      F11  gene was detected, and was then further defined using a CGH array as a
      4q34.2 telomeric deletion of 7 Mb containing 77 genes. We propose that the
      observed recurrent mutations may be considered as  genetic tags  of a population.
      This study highlights the importance of screening for large deletions in
      molecular studies of  F11 .

PMID- 22159457
TI  - Aptamer optical biosensor without bio-breakage using upconversion nanoparticles
      as donors.
AB  - LRET-based optical biosensor of an aptamer-upconversion conjugate was
      constructed. It is demonstrated that photosensitized breakage and damage of
      aptamers are eliminated by employing UCNPs as donors, and the as-designed
      biosensor is specific and sensitive in the detection of ATP.

PMID- 22159459
TI  - Biochemical sensor tubing for point-of-care monitoring of intravenous drugs and
      metabolites.
AB  - In medical facilities, there is strong motivation to develop detection systems
      that can provide continuous analysis of fluids in medical tubing used to either
      deliver or remove fluids from a patient's body. Possible applications include
      systems that increase the safety of intravenous (IV) drug injection and point-of
      care health monitoring. In this work, we incorporated a surface-enhanced Raman
      scattering (SERS) sensor comprised of an array of closely spaced metal nanodomes
      into flexible tubing commonly used for IV drug delivery and urinary catheters.
      The nanodome sensor was fabricated by a low-cost, large-area process that enables
      single use disposable operation. As exemplary demonstrations, the sensor was used
      to kinetically detect promethazine (pain medication) and urea (urinary
      metabolite) within their clinically relevant concentration ranges. Distinct SERS
      peaks for each analyte were used to demonstrate separate detection and co
      detection of the analytes.

PMID- 22159460
TI  - DNA binding protein A expression and methylation status in hepatocellular
      carcinoma and the adjacent tissue.
AB  - We investigated the expression and promoter methylation of dbpA in human
      hepatocellular carcinoma (HCC) and examined their correlation with
      clinicopathological features. In 96 paired samples of HCC and adjacent non
      tumorous liver, and 10 normal liver specimens, dbpA mRNA was quantified by real
      time RT-PCR, and promoter methylation was examined by methylation-specific
      polymerase chain reaction and bisulfite sequencing. The results showed that dbpA
      mRNA expression levels were higher in HCC compared to corresponding non-tumor
      tissues (P<0.01) and higher in non-virus-associated HCC compared to virus
      associated cases (P<0.01). dbpA promoter was methylated in 37.7% of HCC samples
      and the promoter methylation was significantly correlated with the low expression
      of dbpA in non-virus-associated HCC (P<0.01), but not in virus-associated HCC.
      Surprisingly, poor prognosis was more significantly associated with high dbpA
      expression in non-tumorous liver (P=0.018) but not with that in HCC. Non-tumorous
      tissues consist of chronic hepatitis or liver cirrhosis, and these conditions are
      the background of hepatocarcinogenesis, defined as the hypercarcinogenic state.
      Our results suggest that the high expression of dbpA in the hypercarcinogenic
      state is an indicator of poor prognosis.

PMID- 22159461
TI  - Recent trends in molecular beacon design and applications.
AB  - A molecular beacon (MB) is a hairpin-structured oligonucleotide probe containing
      a photoluminescent species (PLS) and a quencher at different ends of the strand.
      In a recognition and detection process, the hybridization of MBs with target DNA
      sequences restores the strong photoluminescence, which is quenched before
      hybridization. Making better MBs involves reducing the background
      photoluminescence and increasing the brightness of the PLS, which therefore
      involves the development of new PLS and quenchers, as well as innovative PLS
      quencher systems. Heavy-metal complexes, nanocrystals, pyrene compounds, and
      other materials with excellent photophysical properties have been applied as PLS
      of MBs. Nanoparticles, nanowires, graphene, metal films, and many other media
      have also been introduced to quench photoluminescence. On the basis of their high
      specificity, selectivity, and sensitivity, MBs are developed as a general
      platform for sensing, producing, and carrying molecules other than
      oligonucleotides.

PMID- 22159462
TI  - Measurement of benzene concentration in urban air using passive sampling.
AB  - The concentration of benzene in urban air in the Tri-City area of Poland (Gdansk
      Sopot-Gdynia, and Tczew) was assessed using diffusive passive samplers
      (Radiello). Samples were collected during a four-year monitoring campaign (2007
      2010) at selected monitoring stations managed by the Agency of Regional Air
      Quality Monitoring in the Gdansk Metropolitan Area (ARMAAG) Foundation. The
      performance of the passive samplers was investigated in a field study that
      measured the benzene concentration in urban air. The results obtained by the
      Radiello samplers were compared with the results obtained using an on-line
      monitor (Chrompack CP 7001). Statistical analysis of the results obtained by the
      two different techniques (passive and on-line) was performed by a linear
      regression method (Student's t-test). The influence of temperature fluctuations
      on the uptake rate behavior of the passive samplers was also investigated.

PMID- 22159464
TI  - Analytical techniques in art, archaeology and conservation science.

PMID- 22159463
TI  - A review of recent developments in the speciation and location of arsenic and
      selenium in rice grain.
AB  - Rice is a staple food yet is a significant dietary source of inorganic arsenic, a
      class 1, nonthreshold carcinogen. Establishing the location and speciation of
      arsenic within the edible rice grain is essential for understanding the risk and
      for developing effective strategies to reduce grain arsenic concentrations.
      Conversely, selenium is an essential micronutrient and up to 1 billion people
      worldwide are selenium-deficient. Several studies have suggested that selenium
      supplementation can reduce the risk of some cancers, generating substantial
      interest in biofortifying rice. Knowledge of selenium location and speciation is
      important, because the anti-cancer effects of selenium depend on its speciation.
      Germanic acid is an arsenite/silicic acid analogue, and location of germanium may
      help elucidate the mechanisms of arsenite transport into grain. This review
      summarises recent discoveries in the location and speciation of arsenic,
      germanium, and selenium in rice grain using state-of-the-art mass spectrometry
      and synchrotron techniques, and illustrates both the importance of high
      sensitivity and high-resolution techniques and the advantages of combining
      techniques in an integrated quantitative and spatial approach.

PMID- 22159465
TI  - Metal-enhanced fluorescent probes based on silver nanoparticles and its
      application in IgE detection.
AB  - In this paper, a novel metal plasmon coupled with an aptamer-nucleotide
      hybridized probe was fabricated and applied for protein detection. The specific
      aptamer and single-strand oligonucleotide were chemically bound to silver
      nanoparticles (AgNPs), and Cy5-labeled, complementary single-strand
      oligonucleotides were hybridized with the particle-bound oligonucleotides. The
      hybridized DNA duplexes were regarded as rigid rods that separated the
      fluorophore Cy5 and the surface of AgNPs to reduce the competitive quenching.
      Using a model system comprising human immunoglobulin E (IgE) as the analyte and
      goat antihuman IgE as immobilized capture antibody on glass slides, we
      demonstrate that the detection performance of the synthetic probe was superior to
      the aptamer-based fluorescent probes. The results showed a good linear
      correlation for human IgE in the range from 10 ng/ml to 6.25 MUg/ml. The
      detection limit obtained was 1 ng/ml, which was 50 times lower than that using
      Cy5 oligonucleotide/aptamer hybrid duplex (Probe2) due to the metal-enhanced
      fluorescence effect. This new strategy opens the possibility for the preparation
      of high-sensitivity detection probes based on metal nanoparticles.

PMID- 22159466
TI  - Optical sensors with molecularly imprinted nanospheres: a promising approach for
      robust and label-free detection of small molecules.
AB  - Molecularly imprinted nanospheres obtained by miniemulsion polymerization have
      been applied as the sensitive layer for label-free direct optical sensing of
      small molecules. Using these particles as the sensitive layer allowed for
      improving response times in comparison to sensors using MIP layers. As a model
      compound, well-characterized nanospheres imprinted against L-Boc-phenylalanine
      anilide (L-BFA) were chosen. For immobilization, a simple concept based on
      electrostatic adsorption was used, showing its applicability to different types
      of surfaces, leading to a good surface coverage. The sensor showed short response
      times, good selectivity, and high reversibility with a limit of detection down to
      60 MUM and a limit of quantitation of 94 MUM. Furthermore, reproducibility,
      selectivity, and long-term stability of the sensitive layers were tested. The
      best results were achieved with an adsorption on aminopropylsilane layers,
      showing a chip-to-chip reproducibility of 22%. Furthermore, the sensors showed no
      loss in signal after a storage time of 1 year.

PMID- 22159467
TI  - Critical assessment of the elemental composition of Corning archeological
      reference glasses by LA-ICP-MS.
AB  - Corning archeological reference glasses A, B, C, and D have been made to simulate
      different historic technologies of glass production and are used as standards in
      historic glass investigations. In this work, nanoseconds (193, 266 nm) and
      femtosecond (800 nm) laser ablation were used to study the elemental composition
      of Corning glasses using laser ablation inductively coupled plasma mass
      spectrometry. The determined concentrations of 26 oxides (Li(2)O, B(2)O(3),
      Na(2)O, MgO, Al(2)O(3), SiO(2), P(2)O(5), K(2)O, CaO, TiO(2), V(2)O(5),
      Cr(2)O(3), MnO, Fe(2)O(3), CoO, NiO, CuO, ZnO, Rb(2)O, SrO, ZrO(2), SnO(2),
      Sb(2)O(5), BaO, PbO, Bi(2)O(3)) are compared with values reported in the
      literature. Results show variable discrepancies between the data, with the
      largest differences found for Cr(2)O(3) in Corning A; Li(2)O, B(2)O(3), and
      Cr(2)O(3) in Corning B; and MnO, Sb(2)O(5), Cr(2)O(3), and Bi(2)O(3) in Corning
      C. The best agreement between the measured and literature values was found for
      Corning D. However, even for this reference, glass re-evaluation of the data was
      necessary and new values for PbO, BaO, and Bi(2)O(3) are proposed.

PMID- 22159468
TI  - Collection of trace metals with cationic surfactant-silica particles followed by
      flotation with an anionic surfactant for seawater analysis.
AB  - The analysis of seawater for trace metals is important for pollution monitoring
      and better understanding of marine systems. The present paper describes an
      efficient preconcentration method for the determination of trace metals in
      seawater. Trace metals [Ni(II), Cu(II), Ga(III), Cd(II), Pb(II), and Bi(III)] in
      1,000 mL of seawater sample were complexed with ammonium
      pyrrolidinedithiocarbamate and sorbed onto silica particles covered with
      cetyltrimethylammonium chloride. After the addition of sodium dodecyl sulfate,
      the particles were floated to the solution surface by bubbling and then collected
      by suction. The trace metals were desorbed with dilute nitric acid and determined
      by inductively coupled plasma-mass spectrometry. The rapid 200-fold
      preconcentration was demonstrated with certified seawater samples.

PMID- 22159469
TI  - Multiplexed quantification of proteins adsorbed to surface-modified and non
      modified microdialysis membranes.
AB  - A simple and straightforward method for discovery and quantification of proteins
      adsorbed onto delicate and sensitive membrane surfaces is presented. The adsorbed
      proteins were enzymatically cleaved while still adsorbed onto the membranes using
      an on-surface enzymatic digestion (oSED). This was followed by isobaric tagging,
      nanoliquid chromatography, and tandem mass spectrometry. Protein adsorption on
      tri-block copolymer Poloxamer 407 surface-modified microdialysis (MD) membranes
      were compared with protein adsorption on unmodified MD membranes. Ventricular
      cerebrospinal fluid (vCSF) kept at 37  degrees C was used as sample matrix. In
      total, 19 proteins were quantified in two biological replicates. The surface
      modified membranes adsorbed 33% less proteins than control membranes and the most
      abundant proteins were subunits of hemoglobin and clusterin. The adsorption of
      clusterin on the modified membranes was on average 36% compared to control
      membranes. The most common protein in vCSF, Albumin, was not identified adsorbed
      to the surface at all. It was also experimentally verified that oSED, in
      conjunction with tandem mass spectrometry can be used to quantify femtomole
      amounts of proteins adsorbed on limited and delicate surfaces, such as MD
      membranes. The method has great potential and can be used to study much more
      complex protein adsorption systems than previously reported.

PMID- 22159470
TI  - Cellular uptake of a fluorescent vanadyl sulfonylcalix[4]arene.
AB  - Vanadyl bearing calix[4]arene ligands have undergone evaluation against several
      cell lines, and show varying degrees of toxicity. For vanadyl complexed to a
      sulfonylcalix[4]arene, monitoring of the strong blue fluorescence revealed slow
      uptake kinetics. The complex is exclusively found in the cytoplasm of the cells
      and uptake is not due to active endocytotic mechanisms.

PMID- 22159471
TI  - Chemopreventive effect of saikosaponin-d on diethylinitrosamine-induced
      hepatocarcinogenesis: involvement of CCAAT/enhancer binding protein beta and
      cyclooxygenase-2.
AB  - Cyclooxygenase-2 (COX-2) and CCAAT/enhancer binding protein beta (C/EBPbeta) have
      been shown to be involved in inflammation and carcinogenesis, and our previous
      study revealed that they were co-overexpressed in human hepatocellular carcinoma
      (HCC) tissue and a positive correlation was found. Saikosaponin-d (SSD), a
      triterpene saponin extracted from Bupleurum falcatum L. (Umbelliferae), is known
      to exert inhibitory effects on COX-2 expression, together with inflammation and
      hepatic fibrosis. These findings prompted us to investigate the chemopreventive
      potential of SSD against hepatocarcinogenesis and its possible molecular
      mechanism in vivo. An experimental model with diethylinitrosamine (DEN)-treated
      Sprague Dawley rats was used in the present study. DEN (50 mg/kg body weight) and
      SSD (2 mg/kg body weight) were intraperitoneally injected weekly and daily,
      respectively. Administration of SSD alone had no side effects. The liver nodule
      formation, tumorous invasion to surrounding organs and increased cellular atypia
      induced by DEN were markedly reduced by SSD in the SSD + DEN group compared with
      the DEN group. On the other hand, immunohistochemical staining demonstrated that
      the expression of COX-2 and C/EBPbeta proteins was significantly increased in
      tumor cells and macrophages of liver tissue from DEN-treated rats, whereas the
      expression of the two proteins was markedly lowered in the SSD + DEN group.
      Overall, our results suggest that SSD prevents DEN-induced hepatocarcinogenesis
      in rats through inhibition of C/EBPbeta and COX-2, providing indispensable
      experimental evidence for the clinical application of SSD as a novel
      chemopreventive agent against HCC in the future.

PMID- 22159472
TI  - Regulatory T-cell-mediated inhibition of antitumor immune responses is associated
      with clinical outcome in patients with liver metastasis from colorectal cancer.
AB  - Adaptive regulatory T cells (Tregs) contribute to an immunosuppressive
      microenvironment in colorectal cancer (CRC). Here, we examined whether the level
      of Treg-mediated inhibition of antitumor immune responses in patients with
      metastatic CRC (metCRC) selected for liver resection is associated with clinical
      outcome. Preoperatively and at follow-ups, we did flow-based phenotyping,
      examined antitumor immunity using peptides from carcinoembryonic antigen (CEA)
      protein in the presence or absence of CD4(+)CD25(+)CD127(dim/-) cells (Tregs) and
      determined cytokine and PGE(2) levels in patient blood samples. At 18 months post
      surgery, 8 patients were disease free (7 alive and 1 dead of unrelated cause) and
      10 had experienced disease recurrence (7 alive and 3 dead of metCRC). Prior to
      surgery, the patients demonstrated Treg-mediated suppression of TNFalpha and
      IFNgamma expression that could be perturbed through the PGE(2)/cAMP pathway and
      the immune suppression was significantly higher in the group that later developed
      disease recurrence (P = 0.046). Furthermore, the post-surgery plasma PGE(2)
      levels were related to the clinical outcome (PGE(2) levels of 280 +/- 47 vs. 704
      +/- 153 pg/ml (mean +/- SEM) for disease free and recurrent disease,
      respectively). T-cell phenotyping revealed higher frequencies of COX-2(+) cells
      in the patients with recurrent disease. These findings support the notion that
      the level of Treg-mediated suppression of adaptive antitumor immune responses at
      the time of surgery may influence later clinical outcome of metCRC and provide
      valuable prognostic information.

PMID- 22159473
TI  - Collective action of hematopoietic cell subsets mediates anti-IL10R1 and CpG
      tumor immunity.
AB  - Based on the specificity of antigen recognition and the ability to generate long
      lived memory responses, cancer immunotherapies primarily target tumor-associated
      T cells. Systemic administration of anti-IL-10R1 antibody in combination with
      local CpG administration has been shown to induce tumor regression in a T-cell
      dependent manner. Here, we confirmed the anti-tumor efficacy of anti-IL-10R1 and
      CpG therapy in the highly aggressive B16F10 melanoma model. However, T cells were
      not required for tumor growth inhibition. Through cellular depletions and genetic
      models of leukocyte deficiency, we demonstrated that T, B, and NK cells, and
      neutrophils are not essential for anti-tumor efficacy. Nevertheless,
      hematopoietic cells as a whole are required for anti-IL-10R1- and CpG-induced
      tumor growth inhibition, suggesting that the collective action of multiple
      subsets of hematopoietic-derived cells is required for anti-tumor efficacy.

PMID- 22159474
TI  - Neutrophil function and apoptosis in patients with chronic hepatitis C treated
      with pegylated interferon alpha and ribavirin.
AB  - The role of neutrophils in the pathogenesis of chronic hepatitis C as well as the
      effect of pegylated interferon alpha (PEG-IFN-alpha) and ribavirin treatment on
      neutrophil function is not precisely known. The study included 32 patients with
      CCH aged between 19 and 58 years (mean 33.5 years). Before and after 12 weeks of
      treatment with Peg-IFN-alpha and ribavirin, intracellular reactive oxygen species
      (ROS) level, expression of adhesion molecules CD11b/MAC-1, CD16, CD18 and CD62L
      on neutrophils, as well as apoptosis and necrosis of these cells were analyzed
      with the use of flow cytometry. During antiviral therapy, a statistically
      significant decrease of mean fluorescence intensity for CD16 high and CD62 and
      increase for CD11b/MAC-1 along with the increased apoptosis and decreased
      necrosis of neutrophils were observed. After 12 weeks of treatment, intracellular
      ROS production by unstimulated neutrophils did not change, but after stimulation
      with phorbol 12-myristate 13-acetate, statistically significant increase of ROS
      level was observed. During PEG-IFN-alpha and ribavirin treatment, activation of
      neutrophil function and increased ROS production were reported, which possibly
      resulted in accelerated apoptosis of these cells.

PMID- 22159475
TI  - Acetylcholine receptor-induced experimental myasthenia gravis: what have we
      learned from animal models after three decades?
AB  - Myasthenia gravis (MG) is an autoimmune disease caused by an immunological
      response against the acetylcholine receptor (AChR) at the neuromuscular junction.
      Anti-AChR antibodies induce degradation of the receptor, activation of complement
      cascade and destruction of the post-synaptic membrane, resulting in a functional
      reduction of AChR availability. The pathophysiological role of autoantibodies
      (auto-Abs) and T helper lymphocytes has been studied in the experimental
      autoimmune MG (EAMG) models. EAMG models have been employed to investigate the
      factors involved in the development of MG and to suggest new therapies aimed to
      preventing or modulating the ongoing disease. EAMG can be induced in susceptible
      mouse and rat strains, which develop clinical symptoms such as muscular weakness
      and fatigability, mimicking the human disease. Two major types of EAMG can be
      induced, passive and active EAMG. Passive transfer MG models, involving the
      injection of auto-Abs, are helpful for studying the role of complement molecules
      and their regulatory proteins, which can prevent neuromuscular junction
      degradation. Active models, induced by immunization, are employed for the
      analysis of antigen-specific immune responses and their modulation in order to
      improve disease progression. In this review, we will concentrate on the main
      pathogenic mechanisms of MG, focusing on recent findings on EAMG experimental
      models.

PMID- 22159476
TI  - Immune regulation by sphingosine 1-phosphate and its receptors.
AB  - It is well established that the lysophospholipid and signalling molecule
      sphingosine 1-phosphate (S1P) has many important functions in immune
      surveillance. S1P is produced from sphingosine by two distinct sphingosine
      kinases, SphK1 and SphK2, and acts as an intracellular messenger and as an
      extracellular ligand of five G protein-coupled cell surface receptors designated
      S1P(1)-S1P(5). S1P not only regulates peripheral lymphocyte circulation, but also
      influences their differentiation, activation, infiltration, and local
      positioning. The therapeutic value of modulating S1P metabolism and S1P receptor
      function is currently tested in clinical trials and holds great promise for
      treatment of different autoimmune diseases. Despite its obvious contribution to
      immune regulation, the analysis of S1P is still challenging. A major obstacle is
      the difficulty to analyze S1P locally in tissues and within cells due to its high
      metabolic turnover and the limited resolution of current analytical techniques
      like liquid chromatography and mass spectrometry. This review focuses on recent
      advancements to our understanding how different sources of S1P contribute to
      immune function, and how changes in production, secretion, and degradation of S1P
      can influence immune responses.

PMID- 22159477
TI  - [Emergencies invisibility].

PMID- 22159478
TI  - [Evaluation of the toxic activity of the pyrethroid insecticides deltamethrin and
      lambdacyhalothrin in two Panamanian field populations of Rhodnius pallescens
      (Hemiptera: Reduviidae)].
AB  - INTRODUCTION: Systematic evaluation of the susceptibility of disease vectors to
      insecticides permits the detection of the development of insecticide resistance
      over time. This is necessary to evaluate the effectiveness of control methods and
      to plan management strategies of the resistance. OBJECTIVE: The baseline
      susceptibility was determined for I and V instar nymphs of Rhodnius pallescens to
      the active ingredients of the insecticides deltamethrin and lambdacyhalothrin.
      MATERIALS AND METHODS: The bioassays were applied to two field populations of R.
      pallescens collected in Chilibre and Cerro Cama, Panama. A standard protocol for
      topical application was adapted from that developed for Rhodnius prolixus.
      Bioassays were performed using topical applications on the dorsal abdominal
      surface, with volumes of 0.1ul and 0.5ul acetone solution of insecticide for
      nymphs of stage I and V respectively, using 5ul and 25ul Hamilton microsyringes
      with a repeating dispenser. Ten nymphs were used for each insecticide
      concentration. Results. With the topical application of lambdacyhalothrin on
      first-instar nymphs from Chilibre and Cerro Cama, the LD50 values expressed in
      ng/insect were 0.13 and 0.11 respectively. In fifth-instar nymphs the LD50 values
      were 1.71 and 3.48, respectively. For deltamethrin, the topical application on
      first-instar nymphs resulted in LD50 values of 0.02 and 0.02, and in fifth-instar
      nymphs the LD50 values were 2.11 and 1.55, respectively. CONCLUSIONS: In I and V
      instar nymphs from the two R. pallescens populations, resistance factor values
      demonstrated no significant difference in the toxic effects of the two
      insecticides and indicated that the R. pallescens populations were susceptible
      them.

PMID- 22159479
TI  - [Distribution of extended spectrum beta-lactamases-codifying genes in Klebsiella
      pneumoniae isolates from hospitals of Bogota, D.C., Colombia].
AB  - INTRODUCTION: Extended spectrum beta-lactamases (ESBL) are the most widely
      distributed enzymes in Enterobacteriaceae of Latin America and are key enzymes in
      resistance to antibiotics in common use. However, in Colombia, little information
      is available concerning the identity of genes coding for these enzymes in
      Klebsiella pneumoniae. OBJECTIVE: The bla genes were identified in K. pneumoniae
      isolated from hospitals in Bogota D.C., Colombia. Materials and methods. One
      hundred seventy-seven isolates of ESBL producers were collected from 10 hospitals
      in Bogota between 2003 and 2005. Antibiotic susceptibility was determined by disk
      diffusion, and the number of beta-lactamases in each isolate was assessed by
      isoelectric focusing. blaCTX-M, blaSHV and blaTEM were identified by PCR and
      subsequent sequencing. RESULTS: Besides, the resitenance to third generation
      cephalosporins, 44.7 % and 49.7 % were resistant to amikacyn and thrimetoprim
      sulaphametoxazole respectively. Lower resistance rates to other antibiotics were
      observed as well. An average of three beta-lactamases were detected by
      isoelectric focusing, and the genes blaCTX-M-12 (56.0%) and blaSHV-12 (33.3%)
      were the most prevalent. blaSHV-5 (11.8%), blaCTX-M-1-1 (4.0%), blaSHV-27 (2.8%),
      blaSHV-2 (2.8%), blaCTX-M-1-2 (1.7%) and blaCTX-M-1-15 (0.6%) were present in
      smaller percentages. In addition, three genes were identified that coded for
      narrow spectrum beta-lactamases. CONCLUSION: Eleven bla genes were identified,
      eight of which were ESBL-coding. The diversity of the bla genes suggested a
      continuing exposure of K. pneumoniae to strong antibiotic pressures in Bogota
      hospitals.

PMID- 22159480
TI  - [Enteric Gram negative rods and unfermented of glucose bacteria in patients with
      peri-implant disease].
AB  - INTRODUCTION: Implants can be colonized by microorganisms from oral biofilms and
      may affect peri-implant tissues health. Among these bacteria, pathogens typically
      associated with periodontitis can be found, such as Aggregatibacter
      actinomycetemcomitans and Porphyromonas gingivalis, as well as Gram negative
      enteric bacilli not typically associated with periodontal diseases. OBJECTIVE:
      Superinfecting bacteria were characterized from peri-implant lesions in patients
      with history of periodontitis. MATERIALS AND METHODS: Sixty-eight implants were
      studied in 55 patients; the average patient age was 56 years. Forty-nine implants
      had peri-implant lesions and 19 were considered stable. Subgingival samples were
      obtained in affected and stable implants. The samples were streaked on Mac-Conkey
      agar and incubated at 37 degrees C for 24 hours. The colonies were identified
      with the kit-BD BBL Crystal E/NF(r). RESULTS: Superinfecting organisms were
      detected in 20 patients--they were seen more frequently at diseased implants
      (n=15) than at healthy implants (n=5). The prevalence of superinfecting bacteria
      on the selected implants was 33.8% (n=23/68). These bacteria were more prevalent
      among affected implants (n=17 or 25%) than those with stable implants n=6 (8.8%).
      Klebsiella pneumoniae was the most frequent Gram negative rod detected (n=12).
      CONCLUSIONS: One-third of the implants had superinfecting organisms. Implants
      with a peri-implant lesion had a higher frequency of superinfecting bacteria.
      Klebsiella pneumoniae was the most common superinfecting organism isolated. A
      multiple infection caused by superinfecting bacteria was present only at diseased
      implants. These microbial agents potentially affect implant stability.

PMID- 22159481
TI  - [Systematic review of antimicrobial resistance among Gram positive cocci in
      hospitals in Colombia].
AB  - INTRODUCTION: Bacterial resistance is a public health problem worldwide whose
      proper management requires knowledge of its presence and its behavior in each
      region and country. OBJECTIVES: A survey of the medical literature was conducted
      to identify levels of resistance to antibiotic markers in Gram positive bacterial
      isolates from Colombian hospitals. MATERIALS AND METHODS: A systematic review of
      the literature included articles indexed in MEDLINE and LILACS. A manual search
      was made of Colombian scientific journals and other infectious disease literature
      not available electronically. RESULTS: A total of 34 observational studies were
      located, including a series of consecutive reports initiated in 2001. Most of the
      reports came from the city of Bogota. The rate of methicillin resistance for
      Staphylococcus aureus and coagulase-negative staphylococci in non intensive care
      unit isolates ranged between 35%-50% and 72%-76%, respectively. Resistance in
      intensive care unit isolates had a range between 35%-71% and 74%-83%,
      respectively. The rate of vancomycin-resistant Enterococcus faecium averaged less
      than 20% over the years but with large annual variation . CONCLUSIONS: Resistance
      markers appeared in high frequency among Gram positive isolates identified in
      hospitals in major Colombian cities.

PMID- 22159482
TI  - [Roll of antibodies antiplatelets in viral infection: a systematic review of
      literature].
AB  - INTRODUCTION: Thrombocytopenia is a frequent phenomenon in viral infections.
      Peripheral platelet destruction mediated by anti-platelet antibodies has been one
      of the proposed causal mechanisms. OBJECTIVE: Results were collected and analyzed
      from published studies on associations of human viral infections on anti-platelet
      antibodies and total platelet counts. MATERIALS AND METHODS: A PubMed search was
      conducted using the following terms: Viral infection (OR Virus diseases) AND
      antiplatelet antibody (OR thrombocytopenia) AND HIV (OR measles OR dengue OR
      chickenpox OR varicella OR Epistein Barr OR mumps OR rubella). Two hundred
      eighteen reference hits were obtained, 65 of which were relevant to this review.
      RESULTS: Antiplatelet antibody-mediated thrombocytopenia has been documented in
      cases of HIV, measles, dengue, chickenpox, Epstein-Barr, mumps and rubella.
      Moreover, the presence of these antibodies has been associated with severity the
      disease and thrombocytopenia in viral infections. CONCLUSIONS: Although the
      presence of antiplatelet antibodies was not the only mechanism for explaining the
      thrombocytopenia developed in these viral infections, their presence was
      associated with severity of thrombocytopenia and with the clinical presentation
      of these patients.

PMID- 22159483
TI  - Differential expression of human beta defensins in placenta and detection of
      allelic variants in the DEFB1 gene from HIV-1 positive mothers.
AB  - INTRODUCTION: Low infection rates in neonates born to HIV-1-seropositive mothers
      highlight the existence of natural defense mechanisms in the maternal-fetal
      interface. Human beta defensins (HBDs) inhibit HIV-1 replication in vitro and
      their variants are associated with HIV-1 resistance/susceptibility. OBJECTIVE:
      Levels of HBD mRNA expression in placentas were obtained from seropositive and
      healthy mothers to determine whether HIV-1 infection induces anti-viral factors.
      Materials and methods. HBD-1, -2 and -3 transcripts were quantified by real time
      RT-PCR, and A692G/G1654A/A1836G variants in the DEFB1 gene were evaluated by
      sequencing. RESULTS: Transcript levels of HBD-1 were significantly higher, and
      those of HBD-3 were lower in placenta from seropositive mothers compared to
      controls. Additionally, simultaneous presence of the A692G A/G and A1836G G/G
      genotypes was associated with high expression of HBD-1 in all populations and the
      A692G variant in babies born to seropositive mothers was in Hardy-Weinberg
      disequilibrium. CONCLUSION: Contrasting results in levels of HBDs were probably
      due to viral stimuli and suggest that HIV-1 induce a differential expression of
      HBDs in placenta and these proteins could be involved in protecting against HIV-1
      at least early in pregnancy. However, it was not possible to associate these
      findings directly with protection against HIV-1 vertical transmission since none
      of the newborn infants became infected.

PMID- 22159484
TI  - [Evaluation of rapid diagnostic tests for malaria in Colombia as an integral part
      of the disease control strategy].
AB  - INTRODUCTION: The Andean Health Organization has been responsible for the
      coordination and evaluation of the malaria rapid diagnostic test strategy. This
      undertaking was organized to strengthen the malaria diagnostic capacity in ten
      provinces of Colombia. OBJECTIVE: The implementation cycle of malaria rapid
      diagnostic tests was evaluated, along with its impact, performance, usage and
      coverage under the project "Malaria control in bordering areas of the Andean
      Region: a community cpproach" (PAMAFRO), as an integral part of the malaria
      control strategy. MATERIALS AND METHODS: A descriptive retrospective study was
      organized in two stages. The first stage was an evaluation of the implementation
      of the rapid diagnostic test cycle. The second stage evaluated indicators of
      impact, performance, usage and coverage of this strategy. These evaluations were
      conducted from October 2007 to July 2008 in 10 Andean provinces of Colombia. A
      multi-criteria scoring method was applied to determine the critical variables.
      RESULTS: The compliance in the implementation cycle for rapid diagnostic tests
      was 71%. Planning was the weakest component of the cycle with 50% of the goals
      accomplished. The critical variables with low compliance were as follows: study
      of rapid diagnostic test needs in the country (50%), study of rapid diagnostic
      test needs in each province (50%), rapid diagnostic test distribution according
      to needs (50%), assessment of health workers performance (50%), compliance with
      temperature and humidity requirements for storage of the rapid diagnostic tests
      at the provincial level (50%), logistics (67%) and supervision (25%). CONCLUSION:
      Implementation strategies are important to strengthen the critical variables
      found asociated with low compliance.

PMID- 22159485
TI  - [Interaction of rotavirus with protein disulfide isomerase in vitro and cell
      system].
AB  - INTRODUCTION: Rotavirus entry process involves a multi-step mechanism, the first
      of which is when the outermost viral proteins interact with four different
      integrins and Hsc70. Recently, rotavirus infection reportedly has been decreased
      after blocking cell surface protein disulfide isomerase (PDI). This suggested
      that this protein interacts with rotavirus during the entry process. OBJECTIVES:
      The aim was to establish the rotavirus-PDI interaction in an in vitro system
      using PDI isolated from bovine liver, and in a cell system consisting of MA104
      cells and mouse small intestinal villi. MATERIALS AND METHODS: Protein disulfide
      isomerase was isolated from a bovine liver homogenate using anti-PDI antibodies
      coupled to agarose through hydrazone bonds. Purity of purified protein was
      assessed by SDS-PAGE and Western blot. The purified PDI was used to study its in
      vitro interaction with the rotavirus particles. This interaction was compared
      with that taking place in MA104 cells and small intestinal villi isolated from
      sucking mice ICR. RESULTS: The purified PDI showed an electrophoretic homogeneity
      and was able to bind rotavirus particles in vitro. Rotavirus-PDI interaction was
      detected by capture ELISA using purified protein and rotavirus strains RRV and
      wild-type ECwt. Interaction between rotavirus particles and cellular PDI was
      detected by ELISA using cell lysates after virus inoculation. CONCLUSIONS:
      Rotavirus-PDI interaction was demonstrated in vitro as well as inMA104 cells and
      intestinal villi from suckling mice.

PMID- 22159487
TI  - [Knowledge and practices about the prevention and the control of the influenza A
      H1N1 in the community of Floridablanca, Santander].
AB  - INTRODUCTION: The influenza A H1N1 generated a pandemic during 2009; governments
      around the world developed mitigation and control strategies to contain its
      spread. In Santander prevention plans in a local community were put into
      practice. OBJECTIVES: The knowledge and practices of the population were assessed
      with respect to the prevention and control of pandemic influenza A H1N1.
      MATERIALS AND METHODS: A cross-sectional study of a random sample of processed
      survey designed by one of the investigators, was conducted by personnel
      experienced with the survey method. Analysis was by univariate, bivariate and
      logistic regression methods. RESULTS: The sample obtained was of 340 inhabitants.
      Nearly the entire population (97.4%) were aware of the pandemic. Hand washing and
      use of surgical masks were the best known preventative actions. An association
      was seen between gender and level of knowledge, and between knowledge of
      preventative action and the media exposure. The educational level was related to
      symptom control measures. Age was related with the duration of hand washing and
      the use of quarantine. CONCLUSIONS: The community appeared to have acceptable
      levels of knowledge and practices for the prevention of influenza A H1N1.
      Continued mitigation plans at government level were recommended to prevent the
      spread of influenza.

PMID- 22159486
TI  - [Mutational frequencies in usherin(USH2A gene) in 26 Colombian individuals with
      Usher syndrome type II].
AB  - INTRODUCTION: Usher syndrome is a disorder characterized by progressive retinitis
      pigmentosa, prelingual sensory hearing loss and vestibular dysfunction. It is the
      most frequent cause of deaf-blindness in humans. Three clinical types and twelve
      genetic subtypes have been characterized. Type II is the most common, and among
      these cases, nearly 80% have mutations in the USH2A gene. OBJECTIVE: The aim of
      the study was to establish the mutational frequencies for the short isoform of
      USH2A gene in Usher syndrome type II. MATERIALS AND METHODS: Twenty-six Colombian
      individuals with Usher syndrome type II were included. SSCP analysis for 20 exons
      of the short isoform was performed and abnormal patterns were sequenced.
      Sequencing of exon 13 of the USH2A gene was performed for all the individuals
      because the most frequent mutation is located in this exon. RESULTS: The most
      frequent mutation was c.2299delG, identified in the 27% (n=8) of the sample. The
      second mutation, p.R334W, showed a frequency of 15%. A new variant identified in
      the 5'UTR region, g.129G>T, was present in 1 individual (4%). Four polymorphisms
      were identified; one of them is a new deletion in exon 20, first reported in this
      study. CONCLUSIONS: Mutations in the usherin short isoform were identified in 38%
      of a sample of 26 USH2 cases. Molecular diagnosis was established in 7 of the 26.

PMID- 22159488
TI  - [Evaluation of atypical semen parameters in individuals whose couples had a
      history of early recurrent embryo death: in search for a reference value].
AB  - INTRODUCTION: Previous studies related alterations in non-conventional seminal
      parameters with recurrent early embryonic death for one couple. A reference
      standard of clinical assessment is required for the management of these kinds of
      patients. OBJECTIVE: Normal semen parameters were established based on functional
      tests including lipid peroxidation of sperm membranes, antioxidant capacity of
      seminal plasma and integrity of sperm chromatin to compare with men whose
      partners have recurrent early embryonic death. These parameters set reference
      values to identify subfertile individuals whose condition can be attributed to
      altered semen parameters. MATERIALS AND METHODS: The conventional and non
      conventional semen parameters of 47 samples of semen were evaluated. Thirty-six
      samples were from subfertile individuals whose partners had a history of early
      recurrent embryo death, and 11 samples were from individuals with recent evidence
      of normal fertility. RESULTS: By discriminant analysis, the two groups were
      classified as follows: a value below 0.50 for 86.1% of individuals in the group
      of recurrent early embryonic death, and a value above 0.50 to classify 81.8% of
      individuals in the group of recent fertility. CONCLUSIONS: This reference value
      of 0.5 based on the results of sperm tests can identify infertile male patients
      whose partners have a history of early embryonic death. This will aid the
      physician to suggest treatments more focused on the possible cause of
      subfertility.

PMID- 22159489
TI  - [Morphometric analysis of Panstrongylus geniculatus (Heteroptera: Reduviidae)
      from Caracas City, Venezuela].
AB  - INTRODUCTION: In recent years, the assassin bug, Panstrongylus geniculatus, has
      been found infected with Trypanosoma cruzi in rural and urban areas of Caracas,
      Venezuela. Although historically this insect has been considered a forest
      species, it has become adapted to more urban artificial environments. OBJECTIVE:
      The presence of sexual dimorphism was determined as an indicator of adaptation to
      domiciles. MATERIAL AND METHODS: By Generalized Procrustes Analysis (GPA) and
      Elliptical Fourier Analysis (EFA), the isometric size and shape of wings, head
      and pronotums of P. geniculatus was assessed for actively and passively captured
      specimens. These were collected within domiciles in urban areas of Petare and
      Altagracia in Caracas City, and from rural or wild environments of Sanare in
      Andres Eloy Blanco in the state of Lara. RESULTS: Sexual dimorphism was observed
      in the Sanare specimens, with female wings consistently larger than male wings.
      Similarly, female wings and heads from bugs captured in Caracas were smaller than
      those of female bugs captured in Sanare. No significative differences in the
      conformation of the pronotum were found between male and female bugs.
      CONCLUSIONS: Based on the assumption that the sexual dimorphism of bugs is
      reflected by smaller size in domesticated triatomines than in wild bugs, the
      conclusion is that Caracas P. geniculatus has become adapted to living indoors.
      This represents an additional risk factor for the Chagas disease transmission in
      Caracas.

PMID- 22159490
TI  - First environmental isolation of Cryptococcus gattii serotype B, from Cucuta,
      Colombia.
AB  - INTRODUCTION: In Cucuta, Cryptococcus gattii serotype B is commonly recovered
      from immunocompetent patients with cryptococcosis, but it has not been recovered
      from the environment in spite of its high incidence which is 77% out of reported
      cases. OBJECTIVE: The aim of this work was to carry out an extensive
      environmental sampling in Cucuta, in an attempt to isolate C. gattii serotype B
      and to expand our knowledge about the ecology and epidemiology of this important
      yeast. MATERIALS AND METHODS: Samples associated with 3,634 trees from 40 zones
      of Cucuta were collected and processed with 28 samples collected near the houses
      of four patients with cryptococcosis caused by C. gattii serotype B. The serotype
      of the recovered isolates was done using multiplex PCR, molecular patterns were
      determined by RFLP of the URA5 gene and mating type was determined using the
      primers MfI+/-U, MfI+/-L, MFa2U and MFa2L. RESULTS: In total, 4,389 samples were
      processed and one isolate of C. gattii serotype B (VGI/a), two isolates of C.
      gattii serotype C (VGIII/I+/-) and three isolates of C. neoformans var. grubii,
      serotype A (VNI/I+/-), were recovered. The density of the recovered isolates
      varied from 50 to 350 cfu/g of soil. CONCLUSIONS: This is the first report on the
      environmental isolation of C. gattii serotype B from Cucuta. However, because of
      the low rate of recovery of isolates from soil only, the environmental niche of
      C. gattii has not been established and further environmental studies in Cucuta
      are necessary, owing that this serotype is not only causing cryptococcosis but
      also has shown a higher virulence after the Vancouver outbreak.

PMID- 22159491
TI  - [Increase in erythromycin-resistant Streptococcus pneumoniae in Colombia, 1994
      2008].
AB  - INTRODUCTION: Streptococcus pneumoniae is a commonly implicated agent in invasive
      disease. For infections of S. pneumoniae resistant to b-lactam, macrolides are an
      alternative treatment. However, resistance to macrolides has increased worldwide
      as well. OBJECTIVE: The frequency of resistance to erythromycin was determined
      for S. pneumoniae over a 15-year surveillance period, and the resistant isolates
      were characterized phenotypically and genotypically. MATERIALS AND METHODS:
      Demographic data of the patients, antimicrobial susceptibility and serotypes were
      analyzed for 3,241 S. pneumoniae isolates recovered between 1994 and 2008. The
      phenotypes were determined by the double-disc technique and genotypes by PCR
      (polymerase chain reaction) and PFGE (pulsed field gel electrophoresis). Isolates
      were recovered from invasive diseases and were provided by national public health
      laboratories. RESULTS: Of the 3,241 isolates, 136 were resistant to erythromycin.
      In the 12-year period between 1994-1996 and 2006-2008, resistance in each 2-year
      sampling had increased from 2.4% to 6.9% in children under 6 years and from 3.3%
      to 5.7% in adults. The most common serotypes were 6B (36.8%), 14 (16.9%) and 6A
      (17.6%). Constitutive phenotype cMLSB was determined in 87 isolates; 82 of these
      expressed the ermB gene. Phenotype M was determined in 46 isolates; 45 had the
      mefA gene. An additional three isolates expressed the inducible phenotype
      (iMLSB), and one expressed the ermB gene. By PFGE, 50 of the isolates were found
      to be related to international clones--58% were Spain6B-ST90, 26% Spain9V-ST156,
      8% Colombia23F-ST338 and 8% Spain23F-ST81. CONCLUSION: The increase in
      erythromycin resistance was primarily related to the mechanism of ribosomal
      methylation. More than half the cases were congeneric with the clone Spain6B-ST90
      that has been circulating in Colombia since 1994.

PMID- 22159492
TI  - [Cyclospora cayetanensis: biology, environmental distribution and transfer].
AB  - Cyclospora cayetanensis is an apicomplexan protozoan that has emerged as an
      important pathogen causing endemic or epidemic diarrheal disease worldwide. In
      industrialized countries, the parasite has been recognized as the causative agent
      of several outbreaks of diarrheal illness mostly associated with produce imported
      from endemic areas. In developing countries, human cyclosporosis is widely
      distributed. Infection rates from 0% to 41.6% have been described in the general
      population. However, the epidemiology, biology, and ecology of C. cayetanensis
      are not fully understood. The life cycle is not completely characterized,
      although it appears to require a single human host to be accomplished. The role
      of animals as natural reservoirs of the parasite remains to be determined. Little
      information is available concerning the environmental distribution and vehicles
      of transmission of C. cayetanensis. Contaminated water, foods or soil can be
      vehicles of spread of the parasite. The significant uncertainties that remain in
      the knowledge of C. cayetanensis highlight the need for continuing research in
      several areas, including its basic biology and environmental distribution.

PMID- 22159493
TI  - [Virtual microscopy systems: analysis and perspectives].
AB  - Microscopy has been constantly evolving since the end of the Twentieth Century,
      with the introduction of new resources which have improved its practice. For
      example, the use of the virtual microscope has reached a high level of maturity;
      it is a synergy among disciplines such as pathology, histology, medical
      informatics and image analysis. This technology has moved forward many paradigms
      in research, diagnosis, education and medical training. The virtual microscopy
      systems require the digitalization of a physical slide, using motorized
      microscopes, pre and post image processing, compression, transmission and
      visualization. This article provides an extensive analysis of each of these
      processes.A The main characteristics of virtual microscopy are presented as well
      as the impact of these systems in image interpretation and in diagnostic
      activities.

PMID- 22159494
TI  - A simple FRET-based modular design for diagnostic probes.
AB  - In recent years, there has been a massive effort to develop molecular probes with
      optical modes of action. Probes generally produce detectable signals based on
      changes in fluorescence properties. Here, we demonstrate the potential of self
      immolative molecular adaptors as a platform for Turn-On probes based on the FRET
      technique. The probe is equipped with identical fluorophore pairs or a
      fluorophore/quencher FRET pair and a triggering substrate. Upon reaction of the
      analyte of interest with the triggering substrate, the self-immolative adaptor
      spontaneously releases the two dye molecules to break off the FRET effect. As a
      result, a new measurable fluorescent signal is generated. The fluorescence
      obtained can be used to quantify the analyte. The modular structure of the probe
      design will allow the preparation of various chemical probes based on the FRET
      activation technique.

PMID- 22159496
TI  - Reconfigurable virtual electrowetting channels.
AB  - Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a
      fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are
      almost always application specific and far from a true "laboratory." The second
      involves electrowetting droplet movement (digital microfluidics), and allows two
      dimensional computer control of fluidic transport and mixing. The merging of the
      two paradigms in the form of programmable electrowetting channels takes advantage
      of both the "continuous" functionality of rigid channels based on which a large
      number of applications have been developed to date and the "programmable"
      functionality of digital microfluidics that permits electrical control of on-chip
      functions. In this work, we demonstrate for the first time programmable formation
      of virtual microfluidic channels and their continuous operation with pressure
      driven flows using an electrowetting platform. Experimental, theoretical, and
      numerical analyses of virtual channel formation with biologically relevant
      electrolyte solutions and electrically-programmable reconfiguration are
      presented. We demonstrate that the "wall-less" virtual channels can be formed
      reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven
      transport in these virtual channels at flow rates up to 100 MUL min(-1) is
      achievable without distortion of the channel shape. We further demonstrate that
      these virtual channels can be switched on-demand between multiple inputs and
      outputs. Ultimately, we envision a platform that would provide rapid prototyping
      of microfluidic concepts and would be capable of a vast library of functions and
      benefitting applications from clinical diagnostics in resource-limited
      environments to rapid system prototyping to high throughput pharmaceutical
      applications.

PMID- 22159495
TI  - Donor-site-related functional problems following anterior cruciate ligament
      reconstruction: development of a self-administered questionnaire.
AB  - PURPOSE: To develop a self-administered questionnaire for the evaluation of donor
      site-related functional problems after anterior cruciate ligament (ACL)
      reconstruction with autograft harvested from the hamstring tendon or patellar
      tendon and to determine the content validity, reliability and preliminary factor
      structure of this new instrument. METHODS: Seven physiotherapists with long
      clinical experience of rehabilitation after ACL reconstruction and 60 patients
      from the target population participated as experts in the developmental stages of
      the questionnaire. Content validity was determined and quantified with the
      content validity index (CVI). Test-retest reliability, internal consistency and
      factor structure were evaluated in another 64 patients reconstructed with an
      autograft. RESULTS: The final questionnaire included 16 items on symptoms and
      function during activities of daily living and exercise. Excellent content
      validity on both item level (I-CVI >= 0.83, range 0.83-1.00) and scale level (S
      CVI = 0.93) was found. The test-retest reliability was good, ICC = 0.94. Internal
      consistency was high, and Cronbach's alpha was 0.92 and 0.94 at each test
      occasion. The principal components analysis yielded a four-component structure.
      CONCLUSIONS: The questionnaire "Donor-site-Related Functional Problems following
      Anterior Cruciate Ligament (ACL) Reconstruction" is a patient-reported
      questionnaire with high content validity and reliability for the evaluation of
      donor-site-related functional problems after ACL reconstruction, with autograft
      harvested from the hamstring tendon or patellar tendon. The results of this study
      support the use of this questionnaire as a standardized outcome measure for both
      research purposes and in clinical settings.

PMID- 22159497
TI  - Community structure, abundance, and activity of methanotrophs in the Zoige
      wetland of the Tibetan Plateau.
AB  - The Zoige wetland of the Tibetan Plateau is a high-altitude tundra wetland and
      one of the biggest methane emission centers in China. In this study,
      methanotrophs with respect to community structure, abundance, and activity were
      investigated in peat soils collected in the vicinity of different marshland
      plants that dominate different regions of the wetland, including Polygonum
      amphibium, Carex muliensis, and Eleocharis valleculosa (EV). 16S rRNA gene and
      particulate methane monooxygenase gene (pmoA) clone library sequence data
      indicated the presence of methanotrophs with two genera, Methylobacter and
      Methylocystis. Methylococcus, like pmoA gene sequences, were also retrieved and
      showed low similarity to those from Methylococcus spp. and thus indicates the
      existence of novel methanotrophs in the Zoige wetland. Quantitative polymerase
      chain reaction (qPCR) assays were used to measure the abundance of methantrophs
      and detected 10(7) to 10(8) of total pmoA gene copies per gram dry weight of soil
      in the three marshes. Group-specific qPCR and reverse transcriptase qPCR results
      found that the Methylobacter genus dominates the wetland, and Methylocystis
      methanotrophs were less abundant, although this group of methanotrophs was
      estimated to be more active according to mRNA/DNA ratio. Furthermore, EV marsh
      demonstrated the highest methanotrophs abundance and activity among the three
      marshes investigated. Our study suggests that both type I and type II
      methanotrophs contribute to the methane oxidation in the Zoige wetland.

PMID- 22159498
TI  - Influences of plant species composition, fertilisation and Lolium perenne
      ingression on soil microbial community structure in three Irish grasslands.
AB  - Semi-natural grassland soils are frequently fertilised for agricultural
      improvement. This practice often comes at a loss of the indigenous flora while
      fast-growing nitrogen-responsive species, such as Lolium perenne, take over.
      Since soil microbial communities depend on plant root exudates for carbon and
      nitrogen sources, this shift in vegetation is thought to influence soil microbial
      community structure. In this study, we investigated the influence of different
      plant species, fertilisation and L. perenne ingression on microbial communities
      in soils from three semi-natural Irish grasslands. Bacterial and fungal community
      compositions were determined by automated ribosomal intergenic spacer analysis,
      and community changes were linked to environmental factors by multivariate
      statistical analysis. Soil type had a strong effect on bacterial and fungal
      communities, mainly correlated to soil pH, as well as soil carbon and nitrogen
      status. Within each soil type, plant species composition was the main influencing
      factor followed by nitrogen fertilisation and finally Lolium ingression in the
      acidic upland and mesotrophic grassland. In the alkaline grassland, however,
      Lolium ingression had a stronger effect than fertilisation. Our results suggest
      that a change in plant species diversity strongly influences the microbial
      community structure, which may subsequently lead to significant changes in
      ecosystem functioning.

PMID- 22159499
TI  - Mono- and ditopic models of binding of a photochromic chromene annelated with an
      18-crown-6 ether with protonated amino acids.
AB  - In this work, the interaction of protonated amino acids with a chromene bearing a
      fused 18-crown-6 ether moiety was studied by UV-vis and NMR spectroscopy. Initial
      closed forms of the chromene form monotopic 1 : 1 complexes, the ammonium group
      being localized inside the crown ether cavity. UV-irradiation leads to
      transformation of the ring-closed species into the ring-opened form. Depending on
      the amino acid length, either ditopic or monotopic 1 : 1 complexes are formed.
      Such complexes are stabilized by the additional H-bonding between the carboxylic
      group of the acid and the carbonyl oxygen atom of the ring-opened form. Cessation
      of the irradiation results in ring-closure to the chromene with concomitant
      change of the complexation mode.

PMID- 22159500
TI  - Array-based identification of common DNA methylation alterations in ulcerative
      colitis.
AB  - Patients with long-standing ulcerative colitis (UC) have higher risk of
      developing colorectal cancer. Albeit the causes remain to be understood,
      epigenetic alterations have been suggested to play a role in the long-term cancer
      risk of these patients. In this work, we developed a novel microarray platform
      based on methylation-sensitive amplified fragment length polymorphism (MS-AFLP)
      DNA fingerprinting. The over 10,000 NotI sites of the human genome were used to
      generate synthetic primers covering these loci that are equally distributed into
      CpG rich regions (promoters and CpG islands) and outside the CpG islands,
      providing a panoramic view of the methylation alterations in the genome. The
      arrays were first tested using the colon cancer cell line CW-2 showing the
      reproducibility and sensitivity of the approach. We next investigated DNA
      methylation alterations in the colonic mucosa of 14 UC patients. We identified
      epigenetic alterations affecting genes putatively involved in UC disease, and in
      susceptibility to develop colorectal cancer. There was a strong concordance of
      methylation alterations (both hypermethylation and hypomethylation) shared by the
      cancer cells of the CW-2 cell line and the non-cancer UC samples. To the best of
      our knowledge, this work defines the first high-throughput aberrant DNA
      methylation profiles of the colonic mucosa of UC patients. These epigenetic
      profiles provide novel and relevant knowledge on the molecular alterations
      associated to the UC pathology. Some of the detected alterations could be
      exploited as cancer risk predictors underlying a field defect for cancerization
      in UC-associated carcinogenesis.

PMID- 22159501
TI  - Potent and selective inhibition of T-cell protein tyrosine phosphatase (TCPTP) by
      a dinuclear copper(II) complex.
AB  - A dinuclear Cu(II) complex, [Cu(2)(MU-IDA)(phen)(3)(NO(3))]NO(3).4H(2)O (phen =
      1,10-phenanthroline, H(2)IDA = iminodiacetic acid), was found to potently and
      selectively inhibit T-cell protein tyrosine phosphatase, and lead to the anti
      proliferation and apoptosis of C6 glioma cells.

PMID- 22159502
TI  - [Prevention of road accidents involving non-motorized traffic participants
      (pedestrians and cyclists) in Germany].
AB  - During a 1-day workshop organized by the German Society of Orthopaedics and
      Traumatology (DGOU) 15 German accident researchers used different approaches to
      improve the effectiveness of accident prevention for pedestrians and bicyclists
      on German roads. The main results of this analysis show: Fatal injuries of
      pedestrians have been significantly reduced by 82% between 1970 (n=6.056) and
      2007 (n=695). Similarly, fatalities of bicyclists have been reduced during the
      same time period from 1,835 to 425 which amount to almost 80%. However, the total
      number of injured cyclists increased almost twice, i.e. from 40,531 (in 1979) to
      78,579 (in 2007) a fact that needs to be analyzed in more detail. Although
      scientifically proven to provide protection against severe head injuries, helmets
      are worn less frequently by adolescents and women as compared to younger children
      and men. Fatalities of bicyclists might be reduced by using Dobli mirrors which
      allow the truck driver to see the bicyclist when turning right. Recently
      developed sensors are able to detect pedestrians walking closely (<2.5 m) and
      warn the truck driver acoustically. Bicycle lanes should be planned for one
      direction only, separated from the pedestrian way and large enough (2.0 m are
      safer than 1.6 m). Traffic education for school beginners and younger children
      should be repeated to be effective. Training for elderly bicyclists in cities
      with heavy traffic would also be reasonable. Active security systems in cars like
      ESP (electronic stability program), BAS (brake assist system), special light
      systems for curves, and night vision utilities are most effective to prevent
      collision with pedestrians and bicyclists. TV spots for bicyclists could help to
      point out dangerous situations and the proven benefits of wearing a helmet in the
      same way as previous campaigns, e.g."The 7th Sense" for car drivers.

PMID- 22159503
TI  - [Is multiple trauma currently affordable?].

PMID- 22159504
TI  - [A new reduction technique for posterior locked shoulder dislocation. Case report
      and technique description].
AB  - The case of a 61-year-old male with posterior dislocation of the right shoulder
      joint is presented and a new technique for closed reduction of posterior locked
      shoulder dislocation is described. The technique involves four steps: in step 1 a
      constant traction is applied on the injured arm, in step 2 the arm is internally
      rotated and in steps 3 and 4  the second arm of the physician is used as a lever
      arm to lateralize and ventralize the shoulder. Lateralization and ventralization
      of the humeral head are essential to engage the humeral head and to pass it
      around the glenoid during reduction. Steps 3 and 4 are performed simultaneously.
      In the presented case the patient suffered a traumatic shoulder dislocation with
      a rim fracture of the glenoid. After reduction the shoulder was stable and
      conservative treatment was performed. A 2 year follow-up examination revealed a
      pain-free and stable shoulder with free range of motion and an Oxford instability
      score of 48 points. The described reduction technique for posterior locked
      shoulder dislocation is a simple and gentle technique, which can be performed
      easily by one person.Presentation of a reduction technique for locked posterior
      shoulder dislocation. Constant traction and internal rotation is performed for
      engaging the locked humeral head. After disengaging the humeral head the
      reduction is performed by using the arm of the physician as a lever arm.

PMID- 22159505
TI  - Effects of cycle stage on regionalised galanin, galanin receptors 1-3, GNRH and
      GNRH receptor mRNA expression in the ovine hypothalamus.
AB  - The neurotransmitter galanin has been implicated in the steroidogenic regulation
      of reproduction based on work mainly conducted in rodents. This study
      investigated the temporal changes in the expression of galanin and its three
      receptor isoforms and GNRH and GNRHR mRNA in specific hypothalamic nuclei known
      to be involved in the regulation of reproductive cyclicity, namely the medial pre
      optic area (mPOA), the rostral mPOA/organum vasculosum of the lamina terminalis,
      the paraventricular nucleus and the arcuate nucleus using an ovine model.
      Following synchronisation of their oestrous cycles, tissues were collected from
      ewes at five time points: the early follicular, mid follicular (MF) and late
      follicular phases and the early luteal and mid luteal phases. The results
      indicated significant differences in regional expression of most of the genes
      studied, with galanin mRNA expression being highest during the MF phase at the
      start of the GNRH/LH surge and the expression of the three galanin receptor
      (GalR) isoforms and GNRH and its receptor highest during the luteal phase. These
      findings are consistent with a role for galanin in the positive feedback effects
      of oestradiol (E(2)) on GNRH secretion and a role for progesterone induced
      changes in the pattern of expression of GalRs in the regulation of the timing of
      E(2)'s positive feedback through increased sensitivity of galanin-sensitive
      systems to secreted galanin.

PMID- 22159507
TI  - Mechanisms of ligand specificity of the mineralocorticoid receptor.
AB  - The mineralocorticoid receptor (MR) differs from the other steroid receptors in
      that it responds to two physiological ligands, aldosterone and cortisol. In
      epithelial tissues, aldosterone selectivity is determined by the activity of
      11beta-hydroxysteroid dehydrogenase type 2, while in other tissues, including the
      heart and regions of the central nervous system, cortisol is the primary ligand
      for the MR where it may act as an antagonist. Clinical trials have demonstrated
      the potential of MR antagonists in the treatment of cardiovascular disease,
      though their use has been limited by concurrent hyperkalaemia. In order to better
      target the MR, an understanding of the structural determinants of tissue- and
      ligand-specific MR activation is needed. Interactions of the MR have been
      identified, which exhibit ligand discrimination and/or specificity. These
      interactions include those of the ligand-binding domain with ligand, with the N
      terminal domain and with putative co-regulatory molecules. Agonist and antagonist
      binding have been characterised using chimeras between the human MR and the
      glucocorticoid receptor or the zebra fish MR together with molecular modelling.
      The interaction between the N-terminus and the C-terminus is aldosterone
      dependent but is unexpectedly antagonised by cortisol and deoxycorticosterone in
      the human MR. Nuclear receptor-mediated transactivation is critically dependent
      on, and modulated by, co-regulatory molecules. Proteins that interact with the MR
      in the presence of either aldosterone or cortisol, but not both, have been
      identified. The successful identification of ligand-specific interactions of the
      MR may provide the basis for the development of novel MR ligands with tissue
      specificity.

PMID- 22159509
TI  - Dose-dependent effect of early antiplatelet therapy in acute ischaemic stroke.
AB  - Antiplatelet agents are essential in treating patients with acute ischaemic
      stroke (AIS) to prevent recurrent ischaemic events. The aim of this study was to
      evaluate the effectiveness of early antiplatelet therapy with different aspirin
      (ASA) dosages in patients with AIS. This observational study included 454
      patients with AIS in whom antiplatelet treatment was initiated. The antiplatelet
      effect was determined by whole blood aggregometry within 48 hours after
      antplatelet therapy was initiated. An impedance change exceeding 0 W after
      stimulation with arachidonic acid was defined as ASA low response (ALR) and >=5 
      Omega in ADP-stimulated specimen as clopidogrel LR. Of the study group 53.5%
      patients were treated with 200 mg ASA orally, 27.5% with 500 mg ASA
      intravenously, 8.6% with 100 mg ASA orally, and 7.7% with 75 mg clopidogrel. A
      dose-dependent antiplatelet effect of ASA treatment was found: 18.4% of patients
      with 500 mg ASA intravenously were ALR, in contrast to 32.5% on 200 mg and 35.9%
      on 100 mg ASA orally. Clopidogrel treatment without a loading dose resulted in a
      high proportion of LR (45.7%). Using the propensity score method revealed a three
      times higher risk for ALR for patients treated with ASA 200 mg [odds ratio 2.99
      (1.55-5.79)] compared to treatment with ASA 500 mg. In conclusion, initiating
      antiplatelet therapy in patients with AIS resulted in a dose-dependent
      insufficient platelet inhibitory effect. Our findings suggest using a loading
      dose of 500 mg ASA intravenously as this seems to be favourable when a sufficient
      early platelet inhibitory effect is wanted.

PMID- 22159510
TI  - Direct characterization of protein oligomers and their quaternary structures by
      single-molecule FRET.
AB  - Using a single-molecule method, we directly distinguish among oligomers from
      monomers to tetramers and determine their quaternary structures. Using this
      method, we found that RecR forms a stable dimer and its oligomeric form is
      modulated by its own concentration and the interaction with RecO.

PMID- 22159511
TI  - In vivo treatment of HCV core-positive HepG2 cells with the transfer of
      recombinant caspase-3 using a 2'-5' OAS promoter.
AB  - Hepatitis C virus (HCV) is one of the most common pathogens causing liver-related
      morbidity and mortality, which affect 170 million individuals worldwide. There is
      no vaccine available, and current therapy is only partially effective. In a
      previous study, we constructed a recombinant caspase-3 expression vector under
      the 2'-5'-oligoadenylate synthetase gene (OAS) promoter (pGL3-OAS-re-caspase-3)
      and demonstrated that it is an effective gene therapy for HCV core-positive liver
      cells in vitro. In the present study, the human hepatoma cell line HepG2 was
      transfected with the pcDNA3.1-HCV-core-EGFP plasmid and selected by G418.
      Expression of HCV core protein was confirmed by RT-PCR and immunocytochemistry.
      Both HepG2-expressing HCV core protein and parental HepG2 cells were inoculated
      subcutaneously into BALB/c mice, respectively. Tumor-bearing mice were treated
      with an intratumoral injection of pGL3-OAS-re-caspase-3. The mice were sacrificed
      after 48 h. The correlation between HCV core and caspase-3 expression in tumor
      tissues was analyzed by immunohistochemical staining and double-label
      immunofluorescence staining. The subcutaneous hepatoma in vivo mouse models
      stably expressing HCV core protein and co-expressing HCV core protein and pGL3
      OAS-re-caspase-3 were established. Double-label immunofluorescence staining
      showed that the percentage of co-expression of both HCV core and caspase-3 was 76
      +/- 6% in the group treated with pGL3-OAS-re-caspase-3. There was a significant
      increase in the number of apoptotic cells in the group treated with the pGL3-OAS
      re-caspase-3 system by terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling and transmission electron microscopy. The results suggest that the
      pGL3-OAS-re-caspase-3 construct can effectively induce apoptosis in HCV core
      positive hepatocytes in vivo. The results presented strongly suggest that the
      transfer of pGL3-OAS-re-caspase-3 is an effective and promising gene therapy
      strategy for HCV infection.

PMID- 22159506
TI  - Sirtuin 1 (SIRT1) and steroid hormone receptor activity in cancer.
AB  - Sirtuins, which are class III NAD-dependent histone deacetylases that regulate a
      number of physiological processes, play important roles in the regulation of
      metabolism, aging, oncogenesis, and cancer progression. Recently, a role for the
      sirtuins in the regulation of steroid hormone receptor signaling is emerging. In
      this mini-review, we will summarize current research into the regulation of
      estrogen, androgen, progesterone, mineralocorticoid, and glucocorticoid signaling
      by sirtuins in cancer. Sirtuins can regulate steroid hormone signaling through a
      variety of molecular mechanisms, including acting as co-regulatory transcription
      factors, deacetylating histones in the promoters of genes with nuclear receptor
      binding sites, directly deacetylating steroid hormone nuclear receptors, and
      regulating pathways that modify steroid hormone receptors through
      phosphorylation. Furthermore, disruption of sirtuin activity may be an important
      step in the development of steroid hormone-refractory cancers.

PMID- 22159512
TI  - Preparation and certification of hijiki reference material, NMIJ CRM 7405-a, from
      the edible marine algae hijiki (Hizikia fusiforme).
AB  - A certified reference material, NMIJ CRM 7405-a, for the determination of trace
      elements and As(V) in algae was developed from the edible marine hijiki (Hizikia
      fusiforme) and certified by the National Metrology Institute of Japan (NMIJ), the
      National Institute of Advanced Industrial Science and Technology (AIST). Hijiki
      was collected from the Pacific coast in the Kanto area of Japan, and was washed,
      dried, powdered, and homogenized. The hijiki powder was placed in 400 bottles
      (ca. 20 g each). The concentrations of 18 trace elements and As(V) were
      determined by two to four independent analytical techniques, including (ID)ICP
      (HR)MS, ICP-OES, GFAAS, and HPLC-ICP-MS using calibration solutions prepared from
      the elemental standard solution of Japan calibration service system (JCSS) and
      the NMIJ CRM As(V) solution, and whose concentrations are certified and SI
      traceable. The uncertainties of all the measurements and preparation procedures
      were evaluated. The values of 18 trace elements and As(V) in the CRM were
      certified with uncertainty (k = 2).

PMID- 22159513
TI  - Polystyrene-coated micropallets for culture and separation of primary muscle
      cells.
AB  - Despite identification of a large number of adult stem cell types, current
      primary cell isolation and identification techniques yield heterogeneous samples,
      making detailed biological studies challenging. To identify subsets of isolated
      cells, technologies capable of simultaneous cell culture and cloning are
      necessary. Micropallet arrays, a new cloning platform for adherent cell types,
      hold great potential. However, the microstructures composing these arrays are
      fabricated from an epoxy photoresist 1002F, a growth surface unsuitable for many
      cell types. Optimization of the microstructures' surface properties was conducted
      for the culture of satellite cells, primary muscle cells for which improved cell
      isolation techniques are desired. A variety of surface materials were screened
      for satellite cell adhesion and proliferation and compared to their optimal
      substrate, gelatin-coated Petri dishes. A 1-MUm thick, polystyrene copolymer was
      applied to the microstructures by contact printing. A negatively charged
      copolymer of 5% acrylic acid in 95% styrene was found to be equivalent to the
      control Petri dishes for cell adhesion and proliferation. Cells cultured on
      control dishes and optimal copolymer-coated surfaces maintained an
      undifferentiated state and showed similar mRNA expression for two genes
      indicative of cell differentiation during a standard differentiation protocol.
      Experiments using additional contact-printed layers of extracellular matrix
      proteins collagen and gelatin showed no further improvements. This micropallet
      coating strategy is readily adaptable to optimize the array surface for other
      types of primary cells.

PMID- 22159514
TI  - Solution-state NMR spectroscopy of famotidine revisited: spectral assignment,
      protonation sites, and their structural consequences.
AB  - Multinuclear one (1D-) and two-dimensional (2D) nuclear magnetic resonance (NMR)
      spectroscopic investigations of famotidine, the most potent and widely used
      histamine H(2)-receptor antagonist, were carried out in dimethyl sulfoxide-d(6)
      (DMSO-d(6)) and water. Previous NMR assignments were either incomplete or full
      assignment was based only on 1D spectra and quantum-chemical calculations. Our
      work revealed several literature misassignments of the (1)H, (13)C, and (15)N NMR
      signals and clarified the acid-base properties of the compound at the site
      specific level. The erroneous assignment of Baranska et al. (J. Mol. Struct.
      2001, 563) probably originates from an incorrect hypothesis about the major
      conformation of famotidine in DMSO-d(6). A folded conformation similar to that
      observed in the solid-state was also assumed in solution, stabilized by an
      intramolecular hydrogen bond involving one of the sulphonamide NH(2) protons and
      the thiazole nitrogen. Our detailed 1D and 2D NMR experiments enabled complete ab
      initio (1)H, (13)C, and (15)N assignments and disproved the existence of the
      sulphonamide NH hydrogen bond in the major conformer. Rather, the molecule is
      predominantly present in an extended conformation in DMSO-d(6). The aqueous acid
      base properties of famotidine were studied by 1D (1)H- and 2D (1)H/(13)C
      heteronuclear multiple-bond correlation (HMBC) NMR-pH titrations. The experiments
      identified its basic centers including a new protonation step at highly acidic
      conditions, which was also confirmed by titrations and quantum-chemical
      calculations on a model compound, 2-[4-(sulfanylmethyl)-1,3-thiazol-2
      yl]guanidine. Famotidine is now proved to have four protonation steps in the
      following basicity order: the sulfonamidate anion protonates at pH = 11.3,
      followed by the protonation of the guanidine group at pH = 6.8, whereas, in
      strong acidic solutions, two overlapping protonation processes occur involving
      the amidine and thiazole moieties.

PMID- 22159515
TI  - Thermal stability of Li2MnO3: from localized defects to the spinel phase.
AB  - The thermal stability of Li(2)MnO(3) has been investigated by the means of
      coupled differential thermal analysis and thermogravimetric analysis associated
      with powder X ray diffraction. Various experiments performed in air and in argon
      allowed us to propose a mechanism of spinel-type defects formation in intergrowth
      with Li(2)MnO(3) when treated in air above 900  degrees C. The fidelity of the
      DIFFaX simulations performed led to the understanding of the influence of the
      existence of spinel type defects intergrowth on X ray and electron diffraction
      patterns. The formation of these defects occurs during cooling and is preceded by
      the formation of LiMnO(2) defects in heating. With sufficiently long thermal
      treatments, defects expand such that a spinel type phase can be observed after
      cooling.

PMID- 22159516
TI  - Droplet-based microfluidic device for multiple-droplet clustering.
AB  - We present a multiple-droplet clustering device that can perform sequential
      droplet trapping and storing. Shape-dependent droplet manipulation in forward and
      backward flows has been incorporated to achieve high trapping and storing
      efficiency in a 10 * 12 array of clustering structures (e.g., storing well,
      storing chamber, trapping well, and guiding track). In the forward flow,
      flattened droplets are trapped in each trapping well. In the backward flow, the
      trapped droplets are released from the trapping well and follow the guiding
      tracks to their corresponding storing wells. The guided droplets float up out of
      the confining channel to the super stratum of the storing chamber due to
      interfacial energy and buoyancy effects. This forward/backward flow-based
      trapping/storing process can be repeated several times to cluster droplets with
      different contents and samples in the storing chambers. We expect that the
      proposed platform will be a valuable tool to study complex droplet-based
      reactions in clustered droplets.

PMID- 22159518
TI  - Activation-induced cell death of memory CD8+ T cells from pleural effusion of
      lung cancer patients is mediated by the type II Fas-induced apoptotic pathway.
AB  - Lung cancer is the second most common form of cancer and the leading cause of
      cancer death worldwide. Pleural effusions, containing high numbers of mononuclear
      and tumor cells, are frequent in patients with advanced stages of lung cancer. We
      reported that in pleural effusions from primary lung cancer, the CD8+ T cell
      subpopulation, and particularly the terminally differentiated subset, is reduced
      compared to that of non-malignant effusions. We analyzed the participation of
      activation-induced cell death (AICD) and extrinsic pathways (type I or II) as
      mechanisms for the decrease in pleural effusion CD8+ T cell subpopulation.
      Pleural effusion or peripheral blood CD4+ and CD8+ T cells, from lung cancer
      patients, were stimulated with anti-CD3 antibody and analyzed for (a) apoptosis
      by annexin-V-binding and TUNEL assay, (b) transcript levels of Fas ligand (FasL)
      and TRAIL by real-time RT-PCR, (c) expression of FasL and TRAIL, measured as
      integrated mean fluorescence intensities (iMFI) by flow cytometry, (d) expression
      of Bcl-2 and BIM molecules, measured as MFI, and (e) apoptosis inhibition using
      caspase-8 and -9 inhibitors. Pleural effusion CD8+ T cells, but not CD4+ T cells,
      from cancer patients underwent AICD. Blocking FasL/Fas pathway protected from
      AICD. Upregulation of FasL and TRAIL expressions was found in pleural effusion
      CD8+ T cells, which also showed a subset of Bcl-2 low cells. In memory CD8+ T
      cells, AICD depended on both extrinsic and intrinsic apoptotic pathways. Hence,
      in the pleural space of lung cancer patients, AICD might compromise the antitumor
      function of CD8+ T cells.

PMID- 22159517
TI  - Potent antitumor effects of combination therapy with IFNs and monocytes in mouse
      models of established human ovarian and melanoma tumors.
AB  - Interferon-activated monocytes are known to exert cytocidal activity against
      tumor cells in vitro. Here, we have examined whether a combination of IFN-alpha2a
      and IFN-gamma and human monocytes mediate significant antitumor effects against
      human ovarian and melanoma tumor xenografts in mouse models. OVCAR-3 tumors were
      treated i.t. with monocytes alone, IFN-alpha2a and IFN-gamma alone or combination
      of all three on day 0, 15 or 30 post-tumor implantation. Mice receiving
      combination therapy beginning day 15 showed significantly reduced tumor growth
      and prolonged survival including complete regression in 40% mice. Tumor volumes
      measured on day 80 in mice receiving combination therapy (206 mm(3)) were
      significantly smaller than those of mice receiving the IFNs alone (1,041 mm(3)),
      monocytes alone (1,111 mm(3)) or untreated controls (1,728 mm(3)). Similarly,
      combination therapy with monocytes and IFNs of much larger tumor also inhibited
      OVCAR-3 tumor growth. Immunohistochemistry studies showed a large number of
      activated macrophages (CD31(+)/CD68(+)) infiltrating into OVCAR-3 tumors and
      higher densities of IL-12, IP10 and NOS2, markers of M1 (classical) macrophages
      in tumors treated with combination therapy compared to the controls.
      Interestingly, IFNs-activated macrophages induced apoptosis of OVCAR-3 tumor
      cells as monocytes alone or IFNs alone did not mediate significant apoptosis.
      Similar antitumor activity was observed in the LOX melanoma mouse model, but not
      as profound as seen with the OVCAR-3 tumors. Administration of either mixture of
      monocytes and IFN-alpha2a or monocytes and IFN-gamma did not inhibit Lox melanoma
      growth; however, a significant inhibition was observed when tumors were treated
      with a mixture of monocytes, IFN-alpha2a and IFN-gamma. These results indicate
      that monocytes and both IFN-alpha2a and IFN-gamma may be required to mediate
      profound antitumor effect against human ovarian and melanoma tumors in mouse
      models.

PMID- 22159519
TI  - Cyst following meniscal repair.
AB  - We present a case of meniscal cyst formation 1 year following a successful
      meniscal repair in a 30-year-old male using a hybrid suture-anchor meniscal
      repair system. Open excision of the cyst revealed it to be in continuity with the
      suture-anchor fragments. The patient made an uneventful recovery. Level of
      evidence V.

PMID- 22159520
TI  - Evaluating rotational kinematics of the knee in ACL-ruptured and healthy patients
      using 3.0 Tesla magnetic resonance imaging.
AB  - PURPOSE: Rotational knee laxity is an important measure in restoring knee
      stability following anterior cruciate ligament (ACL) injury, but is difficult to
      quantify with current clinical tools. The hypothesis of the study is that there
      is greater tibial rotation (TR) in women than men, and also in ACL-deficient than
      healthy knees. METHODS: Sixteen healthy (8 men, 26.8 +/- 6.4 years; 8 women, 26.9
      +/- 3.8 years) and ten ACL-deficient (5 men, 33.6 +/- 10.5 years; 5 women, 36.3
      +/- 10.7 years) subjects received bilateral knee MRI in 15 degrees  of flexion
      using a custom device to apply a constant axial compressive load (44 N). A
      rotational torque (3.35 Nm) was sequentially applied to obtain images at internal
      and external rotation positions. T (2)-weighted images were acquired in internal
      and external rotation. Images were segmented and TR was calculated. To assess
      reproducibility, six knees were scanned twice on separate days. Group comparisons
      were made with unpaired t tests, while intrasubject comparisons were made using
      paired t tests. RESULTS: Healthy women demonstrated greater TR than men (13.6
      degrees  +/- 4.7 degrees  vs. 8.3 degrees  +/- 3.6 degrees ; P = 0.001). Male ACL
      deficient knees showed greater TR than the contralateral knee (15.7 degrees  +/-
      6.9 degrees  vs. 7.7 degrees  +/- 5.6 degrees ; P = 0.003), and compared to male
      controls (P = 0.002). ACL-deficient women showed greater TR compared to their
      contralateral leg (15.1 degrees  +/- 2.3 degrees  vs. 10.0 degrees  +/- 4.3
      degrees ; P = 0.01). The intraclass correlation coefficient of the TR measurement
      was 0.913, and the SEM = 1.1 degrees . CONCLUSIONS: Kinematic MRI is a
      reproducible method to quantify total knee rotation. Women have more rotational
      laxity than men, particularly in the external rotation position. ACL rupture
      leads to increased rotational laxity of the knee. LEVEL OF EVIDENCE:
      Retrospective case-control series, Level III.

PMID- 22159521
TI  - Effects of four different surgical approaches on intra-operative joint gap in
      posterior-stabilized total knee arthroplasty.
AB  - PURPOSE: The effects of surgical approaches and patellar positions on joint gap
      measurement during total knee arthroplasty (TKA) remain unclear. We hypothesized
      that joint gap changes with different knee flexion angles would not be consistent
      within four different approaches and two different patellar positions. METHODS:
      This study enrolled 80 knees undergoing posterior-stabilized TKA. For 60 varus
      knees, parapatellar, midvastus, and subvastus approaches were used in 20 knees
      each. For 20 valgus knees, a lateral subvastus approach was used. Component gap
      length and inclination were measured intra-operatively using a specific tensor
      device under 40 lb with the patella reduced or shifted laterally, at 0 degrees ,
      45 degrees , 90 degrees , and 135 degrees  of knee flexion. RESULTS: Mean gap
      lengths at 45 degrees  and 90 degrees  of knee flexion were significantly larger
      with the parapatellar approach than with midvastus or lateral subvastus
      approaches (P < 0.05). Regarding gap inclination, varus angle increased linearly
      through the entire arc of flexion in all four approaches. When the patella was
      shifted laterally, gap lengths at 45 degrees , 90 degrees , and 135 degrees  were
      significantly reduced compared with those for the patella reduced in the
      subvastus approach, whereas gap length was constant in the parapatellar approach,
      regardless of patellar position. CONCLUSION: Joint gap kinematics was not
      consistent within four different approaches and two different patellar positions.
      Relatively large gaps at 45 degrees  and 90 degrees  were unique features for the
      parapatellar approach. Surgeons should be aware that the flexion gap is reduced
      when the patella is shifted laterally in vastus medialis-preserving approaches
      such as the subvastus approach. LEVEL OF EVIDENCE: II.

PMID- 22159522
TI  - A CT-based classification of prior ACL femoral tunnel location for planning
      revision ACL surgery.
AB  - PURPOSE: The purposes of this study are to describe an ACL femoral tunnel
      classification system for use in planning revision ACL reconstruction based on 3
      D computed tomography (CT) reconstructions and to evaluate its inter- and intra
      rater reliability. METHODS: A femoral tunnel classification system was developed
      based on the location of the femoral tunnel relative to the lateral intercondylar
      ridge. The femoral tunnel was classified as Type I if it was located entirely
      below and posterior to the ridge as viewed from distally, Type II if it was
      slightly malpositioned (either vertically, anteriorly, or both), and Type III if
      it was significantly malpositioned. To evaluate the reproducibility of the
      classification system, CT scans of 27 knees were obtained from patients scheduled
      for revision ACL reconstruction, and 3-D reconstructions were created. Four views
      of the 3-D reconstruction of each femur were then obtained, and inter- and intra
      observer reliability was determined following classification of the tunnels by
      eight observers. RESULTS: Twenty-five tunnels were classified as Type I (5
      tunnels), Type II (9 tunnels), or type III (11 tunnels) by at least 5 of 8
      observers, while insufficient agreement was noted to classify two tunnels. The
      interobserver reliability of tunnel classification as type I, II, or III yielded
      a kappa coefficient of 0.57, while intra-observer reliability yielded a kappa
      coefficient of 0.67. Subclassification of type II femoral tunnels into the
      subgroups anterior, vertical, and both was possible in four of the nine type II
      patients. The interobserver reliability of the complete classification system
      yielded a kappa coefficient of 0.50, while the intra-observer reliability yielded
      a kappa coefficient of 0.54. CONCLUSION: Classification of the location of ACL
      femoral tunnels utilizing 3-D reconstructions of CT data yields moderate to
      substantial inter- and intra-observer reliability. LEVEL OF EVIDENCE: Diagnostic
      Level III.

PMID- 22159523
TI  - Genetics and molecular epidemiology of multiple myeloma: the rationale for the
      IMMEnSE consortium (review).
AB  - There is strong evidence suggesting the presence of a genetic component in the
      aetiology of multiple myeloma (MM). However no genetic risk factors have been
      unequivocally established so far. To further our understanding of the genetic
      determinants of MM risk, a promising strategy is to collect a large set of
      patients in a consortium, as successfully done for other cancers. In this
      article, we review the main findings in the genetic susceptibility and
      pharmacogenetics of MM and present the strategy of the IMMEnSE (International
      Multiple Myeloma rESEarch) consortium in contributing to determine the role of
      genetic variation in pharmacogenetics and in MM risk.

PMID- 22159524
TI  - Vancomycin-loaded nano-hydroxyapatite pellets to treat MRSA-induced chronic
      osteomyelitis with bone defect in rabbits.
AB  - OBJECTIVE: To investigate nano-hydroxyapatite (nHA) pellets as carriers for
      vancomycin in the treatment of chronic osteomyelitis and bone defects due to
      methicillin-resistant Staphylococcus aureus (MRSA) strains. METHODS: Chronic
      osteomyelitis was induced in 45 New Zealand white rabbits. After 3 weeks (chronic
      infection), all animals were treated with debridement. The rabbits were divided
      into an experimental group (the bone was filled with vancomycin-loaded nHA
      pellets), a control group (the bone was filled with nHA pellets alone), and a
      blank group. The drug release profiles were determined in vitro and in vivo. X
      rays, bone specimens, and microorganism cultures were used to evaluate the
      efficacy of the treatments. RESULTS: Following a rapid initial release into the
      circulation, the drug concentration remained effective in the osseous and soft
      tissues for 12 weeks after debridement. Within 3 months, all rabbits in the
      experimental group recovered from osteomyelitis without a recurrence of the
      infection and the bone defects were partially repaired, whereas the infection and
      bone defects persisted in the control and blank groups. CONCLUSIONS: The results
      demonstrate that vancomycin-loaded nHA pellets successfully repair bone defects
      and control infection in MRSA-induced chronic osteomyelitis. In addition, nHA is
      an effective and safe controlled-release vancomycin carrier for chronic
      osteomyelitis with bone defects that is induced by MRSA.

PMID- 22159525
TI  - Clickosomes--using triazole-linked phospholipid connectors to fuse vesicles.
AB  - Two complementary artificial diether phospholipids were synthesized that can
      undergo a Cu(I)-catalyzed Huisgen-Sharpless click reaction. The resulting lipid
      can bridge the membranes of large unilamellar vesicles and cause their
      aggregation and ultimately their fusion.

PMID- 22159527
TI  - Acidosis downregulates platelet haemostatic functions and promotes neutrophil
      proinflammatory responses mediated by platelets.
AB  - Acidosis is one of the hallmarks of tissue injury such as trauma, infection,
      inflammation, and tumour growth. Although platelets participate in the
      pathophysiology of all these processes, the impact of acidosis on platelet
      biology has not been studied outside of the quality control of laboratory
      aggregation assays or platelet transfusion optimization. Herein, we evaluate the
      effect of physiologically relevant changes in extracellular acidosis on the
      biological function of platelets, placing particular emphasis on haemostatic and
      secretory functions. Platelet haemostatic responses such as adhesion, spreading,
      activation of alphaIIbbeta3 integrin, ATP release, aggregation, thromboxane B2
      generation, clot retraction and procoagulant activity including
      phosphatidilserine exposure and microparticle formation, showed a statistically
      significant inhibition of thrombin-induced changes at pH of 7.0 and 6.5 compared
      to the physiological pH (7.4). The release of alpha granule content was
      differentially regulated by acidosis. At low pH, thrombin or collagen-induced
      secretion of vascular endothelial growth factor and endostatin were dramatically
      reduced. The release of von Willebrand factor and stromal derived factor-1alpha
      followed a similar, albeit less dramatic pattern. In contrast, the induction of
      CD40L was not changed by low pH, and P-selectin exposure was significantly
      increased. While the generation of mixed platelet-leukocyte aggregates and the
      increased chemotaxis of neutrophils mediated by platelets were further augmented
      under acidic conditions in a P-selectin dependent manner, the increased
      neutrophil survival was independent of P-selectin expression. In conclusion, our
      results indicate that extracellular acidosis downregulates most of the
      haemostatic platelet functions, and promotes those involved in amplifying the
      neutrophil-mediated inflammatory response.

PMID- 22159528
TI  - Near-infrared chiro-optical effects in metallogels.
AB  - A series of novel metallogelators containing near-IR nickel-bis(dithiolene)
      absorbers were rationally designed and synthesized. Robust gel networks are
      formed by right handed helical 1D-nanofibers which generate strong and remarkable
      chiro-optical effects in the near-infrared region.

PMID- 22159529
TI  - [Avulsion fracture of the patella with intra-articular dislocation : a rare form
      of injury to the growing skeleton].
AB  - Sleeve avulsion fractures of the patella in children are a rare condition. We
      present a patient history of an unusual case of an irreducible avulsion fracture
      with intra-articular dislocation including the surgical management and a review
      of the literature.

PMID- 22159530
TI  - [Global access to medications in the actual international context ].

PMID- 22159531
TI  - [Clinical application of diffusion tensor imaging and tractography in a child
      with holoprosencephaly].
AB  - Diffusion tensor imaging and fiber tracking can be methods used for the study of
      congenital brain malformations associated to white matter bundle
      abnormalities.Their use is illustrated in a child with semilobar
      holoprosencephaly in whom diffusion tensor imaging and tractography showed
      diencephalic ventral induction failure and abnormal white matter fascicles in
      brain and brainstem.

PMID- 22159526
TI  - Bacterial, archaeal and fungal succession in the forefield of a receding glacier.
AB  - Glacier forefield chronosequences, initially composed of barren substrate after
      glacier retreat, are ideal locations to study primary microbial colonization and
      succession in a natural environment. We characterized the structure and
      composition of bacterial, archaeal and fungal communities in exposed rock
      substrates along the Damma glacier forefield in central Switzerland. Soil samples
      were taken along the forefield from sites ranging from fine granite sand devoid
      of vegetation near the glacier terminus to well-developed soils covered with
      vegetation. The microbial communities were studied with genetic profiling (T
      RFLP) and sequencing of clone libraries. According to the T-RFLP profiles,
      bacteria showed a high Shannon diversity index (H) (ranging from 2.3 to 3.4) with
      no trend along the forefield. The major bacterial lineages were Proteobacteria,
      Actinobacteria, Acidobacteria, Firmicutes and Cyanobacteria. An interesting
      finding was that Euryarchaeota were predominantly colonizing young soils and
      Crenarchaeota mainly mature soils. Fungi shifted from an Ascomycota-dominated
      community in young soils to a more Basidiomycota-dominated community in old
      soils. Redundancy analysis indicated that base saturation, pH, soil C and N
      contents and plant coverage, all related to soil age, correlated with the
      microbial succession along the forefield.

PMID- 22159532
TI  - [Cold urticaria: case series and literature review].
AB  - Cold urticaria is one of the five most common causes of chronic urticaria and is
      grouped as a physical urticaria. It can occur after exposure to cold, either
      through solid objects, air or liquids. Patients may have symptoms of urticaria,
      angioedema, respiratory distress and even anaphylaxis when the skin is exposed to
      a cold environment, such as handling refrigerated objects, swimming in cold water
      or entering an air-conditioned room. Five cases of cold urticaria are presented,
      followed by a brief literature review.

PMID- 22159533
TI  - [Using S35-S36 and TcH2AF-R primer-based PCR tests to follow-up a Chagas' disease
      patient who had undergone a heart transplant].
AB  - INTRODUCTION: Cardiomyopathy is the most common clinical form of Chagas' disease
      in Colombia, and one treatment option is a heart transplant. Tracking the
      behavior of the Chagas' parasite, Trypanosoma cruzi, is a priority due to the
      risk of post-transplant reactivation of the infection. OBJECTIVE: A case is
      presented of a patient who had suffered from dilated chagasic cardiopathy and
      cardiac failure, and had subsequently undergone heart transplant. The case was
      monitored by PCR, histopathological and echocardiographic examinations. MATERIALS
      AND METHODS: Blood samples were drawn before and after the transplant, and post
      transplant endomyocardial biopsies were taken. The extracted DNA was amplified
      with the TcH2AF-R and S35-S36 primers. Parasitemia was examined by the
      microhematocrit test. In addition, histopathological studies determined the
      parasite presence and transplant rejection status. Echocardiograms were
      administered to evaluate cardiac function. RESULTS: Of the blood samples taken 83
      and 48 days pre-transplant, the latter was positive by the S35-S36 PCR test. PCR
      tests in blood with both primers were negative up to the second month post
      transplant. However, both PCR tests were positive by the third month post
      transplant. Thereupon, the patient was treated with nifurtimox. Both tests
      presented negative results in blood 35 days after treatment was started and
      remained negative thereafter at 0, 3, 10 and 12 months post-treatment. The
      pathology, microhematocrit, and PCR test results from biopsies were negative on
      all the specified dates. CONCLUSIONS: PCR tests were used as indicators of a
      reactivation of trypanosomid infection in the patient. After treatment
      administration, PCR tests became negative. The patient's clinical evolution was
      favorable.

PMID- 22159534
TI  - [Probable outbreak of oral transmission of Chagas disease in Turbo, Antioquia].
AB  - INTRODUCTION: Chagas' disease is endemic in 21 countries of South and Central
      America, including Colombia, where 700,000 to 1.2 million persons are infected
      and eight millions are at risk. In endemic areas, chronic cases are predominant.
      However, in recent years, increasing reports of acute oral transmission have
      appeared. Objective. An outbreak of acute Chagas' disease was verified in the
      municipality of Turbo (Antioquia), and the most probable cause of transmission
      was determined in order to establish prevention and control measures. MATERIALS
      AND METHODS: A descriptive study was done. A search for information from local
      health authorities was conducted to uncover all case reports. Laboratory tests,
      risk factor analysis and search for vectors and reservoirs were undertaken in
      Turbo. RESULTS: Of the 156 people evaluated, 11 cases of acute Chagas' disease
      were identified. Ten had significant titers of IgM and IgG antibodies against the
      Trypanosoma cruzi parasite by IFAT and Elisa tests; one fatal case was linked
      epidemiologically. In 3 cases, PCR was positive for T. cruzi, two of which
      displayed Chagas cardiomyopathy, and one with acute fever. Four cases required
      specialized health care for acute cardiomyopathy. All positive cases had a common
      source of food. One specimen of the triatomid vector species, Panstrongylus
      geniculatus, and one reservoir, the woolly opossum Caluromys lanatus, were
      collected; both were negative to T. cruzi. CONCLUSIONS: An outbreak of acute
      Chagas' disease occurred in Turbo, Antioquia. The mode of transmission may have
      occurred by the ingestion of T. cruzi-contaminated food by infected triatomines
      or opossum feces.

PMID- 22159535
TI  - Perirectal block for out-patient anorectal surgery: a new technique.
AB  - INTRODUCTION: Perirectal block using four puncture places has been classically
      described for rectal surgery. OBJECTIVE: This paper was aimed at showing the
      quality of anesthesia and postoperative analgesia using a new two-puncture-site
      technique. MATERIALS AND METHODS: Patients scheduled for ambulatory rectal
      surgery between January/2003 and December/2007 were included consecutively. The
      new two-puncture technique was used. Alternative anesthetic management and level
      of postoperative pain requirements were evaluated (rated visual analogue scale
      VAS). Follow-up was done by telephone between 1st and 10th postoperative day to
      evaluate complications, pain (yes/no), and satisfaction level (1-5 points score).
      RESULTS: Four hundred and nine subjects were included; 50.61% were female. Mean
      age was 43 (95%CI: 41-44; range: 17-85), 12.7% were aged over 60. According to
      the American Society of Anesthesiology (ASA), 72.6% were classified as ASA1 and
      26.1% ASA2. External and internal hemorrhoidectomy was performed on 31% of
      patients; 61.6% had two or more procedures. Lidocaine was used on 406 subjects.
      Ropivacaine was added for 9.2% of them and levobupivacaine for 89.4%. 394
      patients were followed-up. Median follow-up was 4 days. A response was obtained
      from 346 subjects (84.6%); 105 (30.3%) recalled having suffered pain during the
      post-operative period, being most frequent in the lidocaine+ropivacaine group
      (17/39, 43.5%) than in the lidocaine+bupivacaine group (88/307, 28.6%).
      Satisfaction was evaluated by 336 subjects (82.1%), 332 of them (98.8%) awarding
      a score of 5. Two subjects (0.6%) scored this 2 and 1. Subjects did not mention
      complications. CONCLUSIONS: The new peri-rectal two-puncture block technique is
      easy and also provides analgesia and a high degree of satisfaction.

PMID- 22159536
TI  - [Venous thromboembolism prophylaxis in Colombian surgical and medical patients:
      results for Colombia of the ENDORSE study].
AB  - INTRODUCTION: More information is needed on the risk of venous thromboembolism in
      the hospital setting, and on patterns of use of thromboprophylaxis, as advocated
      in consensus guidelines. ENDORSE was an international study aimed at evaluating
      hospital venous thromboembolism prevention practices in medical and surgical
      patients. OBJECTIVES: The risk of venous thromboembolism was evaluated along with
      the use of thromboprophylaxis in hospitalized medical and surgical subjects;
      these data were compared with the international sample from the ENDORSE study.
      MATERIALS AND METHODS: Participating institutions in Colombia were selected
      arbitrarily. The medical charts for medical and surgical patients were evaluated
      randomly. The 2004 American College of Chest Physician guidelines were used to
      evaluate risk of venous thromboembolism and adherence to recommended
      thromboprophylaxis regimens. RESULTS: The study included 761 subjects (218
      surgical, 543 medical) located in five acute care hospitals; 49% of these
      subjects were considered at risk of venous thromboembolism (40% medical, 72%
      surgical), compared with 52% in the international sample. Prophylaxis use was
      higher in medical patients at risk (63.7%, n=137) than in surgical patients
      (48.4%, n=76; p=0.01). Compared with the international sample, the use of
      prophylaxis in Colombia was greater in medical patients (63.7% vs. 39.5%,
      p=0.003), but lower in surgical patients (48.4% vs. 58.5%, p=0.02). CONCLUSIONS:
      Participating Colombian centers treat patients at risk of venous thromboembolism
      similarly to other participant countries, but appropriate prophylaxis was
      prescribed more frequently to medical patients. Greater efforts are needed, both
      in Colombia and around the world, to improve rates of appropriate venous
      thromboembolism prophylaxis in at-risk subjects.

PMID- 22159537
TI  - [Paragonimus sp. in crabs and awareness of the educational community to aquatic
      ecosystems in La Miel and La Clara, Caldas, Antioquia].
AB  - INTRODUCTION: Previous research has demonstrated the presence of Paragonimus spp.
      in crabs of three municipalities located in the Medellin river basin. To design a
      plan for the control and prevention of paragonimosis, parasite presence must be
      demonstrated in the upper area of the river, and an awareness campaign of its
      risks must involve the participation of the educational community in focusing
      attention on the local aquatic resources. OBJECTIVE: The presence of Paragonimus
      spp. metarcercariae was established in freshwater crabs from La Miel and La Clara
      streams, and an awareness campaign created public awareness to management of the
      aquatic ecosystems for risk reduction. MATERIALS AND METHODS: Nine crabs were
      collected from streams of La Miel and La Clara villages in 2007 and 2008. The
      crabs were indentified, sacrificed in the laboratory and examined for presence of
      Paragonimus spp. metacercariae. Five workshops were conducted with students of
      educational institutions of the two villages to improve the student perception of
      paragonimosis risks associated with the local streams. RESULTS: The crabs were
      identified as Hypolobocera bouvieri. One crab was found with Paragonimus spp. in
      La Miel. A mollusk, Aroapyrgus colombiensis, another host of the parasite was
      found in La Clara. That aquatic ecosystems are a great attraction for the local
      was well established. CONCLUSIONS: Foci of Paragonimus spp. flatworms are present
      in the upper area of Medellin river which includes Caldas. However, local school
      children were uninformed about the risk of paragonimosis associated with the
      local aquatic ecosystem. Therefore this province must be included in programs for
      prevention and control of paragonimosis. The prevalence of this disease
      recommends educational programs that promote awareness of local aquatic
      ecosystems and their parasitic inhabitants.

PMID- 22159538
TI  - [Surveillance of Rickettsia sp. infection in capybaras (Hydrochoerus
      hydrochaeris) a potential model of epidemiological alert in endemic areas].
AB  - INTRODUCTION: Capybaras (Hydrochoerus hydrochaeris) are considered amplifying
      hosts of Rickettsia sp. These rodents are usually parasitized by the tick vector,
      Amblyomma cajennense, the main vector of rickettsioses in humans and animals in
      South America. Capybaras can be used as sentinels in detection of circulation of
      rickettsiae. OBJECTIVE: Antibodies to rickettsiae of spotted fever group were
      detected in capybaras in a rural area of Cordoba Province, northern Colombia.
      MATERIALS AND METHODS: Sera were analyzed from 36 capybaras in a rural area of
      Monteria (village of San Jeronimo) in Cordoba. For the detection of IgG
      antibodies, indirect immunofluorescence was performed. The antigens were derived
      from R. rickettsia strain Taiacu isolated in Brazil. Capybara sera were diluted
      1:64 for IFA analysis. Ticks were collected from each capybara (also known as
      chiguiro) and identified to species. RESULTS: The seroprevalence of spotted fever
      group Rickettsia was 22% (8 capybaras). Four sera had a titer of 1:64, 3 had a
      titer of 1:128 and one serum had a titer of 1:512. All ticks removed from the
      capybaras (n=933) were taxonomically identified as Amblyomma cajennense.
      CONCLUSION: Colombia has areas endemic for rickettsioses, as indicated by
      confirmed annual outbreaks. The current study reports the first evidence of
      natural rickettsial infection of the spotted fever group in capybaras from
      Colombia. The findings suggest that capybaras can be used as sentinels for the
      circulation of rickettsiae and can identify endemic areas for the transmission of
      rickettsial diseases.

PMID- 22159539
TI  - [Microscopic diagnosis of Pneumocystis jirovecii pneumonia in bronchoalveolar
      lavage and oropharyngeal wash samples of immunocompromised patients with
      pneumonia].
AB  - INTRODUCTION: The diagnosis of Pneumocystis jirovecii pneumonia is based on
      observation of the microorganism using several staining techniques in respiratory
      samples, especially bronchoalveolar lavage and induced sputum. Recently, the
      fungus also has been detected in oropharyngeal wash samples, but only using
      molecular tests. OBJECTIVE: The diagnostic yield of two microscopic stains,
      toluidine blue O and direct fluorescent antibody, was compared in bronchoalveolar
      lavage and oropharyngeal wash samples for the detection of P. jirovecii in
      immunocompromised patients with pneumonia. MATERIALS AND METHODS: Cross-sectional
      evaluation diagnostic tests were used in 166 immunosuppressed patients with
      suspected P. jirovecii. By protocol, bronchoscopic bronchoalveolar lavage and
      oropharyngeal wash samples were prepared by cytocentrifugation, and slides were
      stained with toluidine blue and fluorescent antibody. The proportion of positive
      results from each stain and concordance between them were determined. RESULTS:
      Twenty-four cases (14.5%) of P. jirovecii were detected in bronchoalveolar lavage
      samples. Of them, 21 were positive by both toluidine blue and fluorescent
      antibody stains, whereas 3 cases were detected by fluorescent antibody alone.
      None of the 166 oropharyngeal wash samples were positive by either of these
      techniques. No significant differences were found between proportions from
      positive results (p=0.63). Concordance (kappa coefficient) between both stains
      was 0.92 (95% CI: 0.84-1.00). CONCLUSIONS: Both techniques were useful to
      diagnose P. jirovecii in bronchoalveolar lavage samples. However, toluidine blue
      stain did not detect 12% of fluorescent antibody positive cases. Oropharyngeal
      wash samples do not provide sufficient material for the microscopic
      identification of this fungus.

PMID- 22159540
TI  - [Inotropic activity induced by carbamazepine-alkyne derivative in an isolated
      heart model and perfused to constant flow].
AB  - Inotropic activity induced by carbamazepine-alkyne derivative in an isolated
      heart model and perfused to constant flow Introduction. Few data exist with
      respect to the effects of carbamazepine and its derivatives at cardiovascular
      level; furthermore, the molecular mechanisms and cellular site of action are
      still unclear. Objective. The effects induced by carbamazepine-alquine derivative
      on perfusion pressure, vascular resistance and left ventricular pressure were
      evaluated. Materials and methods. The effects of carbamazepine and carbamazepine
      alquine on the perfusion pressure, vascular resistance and left ventricular
      pressure were examined in isolated rat hearts (Langendorff model). Results. Four
      results were obtained: (1) The carbamazepine-alquine derivative 10-9 mM increased
      the perfusion pressure and vascular resistance in comparison with the
      carbamazepine 10-9 mM; (2) the effect of carbamazepine-alquine derivative 10-9-10
      4 mM on left ventricular pressure not was inhibited by metoprolol or prazosin at
      a dose of 10-6 mM; (3) nifedipine 10-6 mM blocked the effects exerted by the
      carbamazepine-alquine derivative 10-9-10--4 mM on left ventricular pressure, and
      (4) the carbamazepine-alquine derivative at dose of 10-9 mM increased the
      concentration of intracellular calcium over a time period of 3-18 min;
      nevertheless, in presence of nifedipine 10-6 mM this effect was inhibited
      significantly (p=0.005). Conclusions. The activity exerted by carbamazepine
      alquine derivative on perfusion pressure, vascular resistance and left
      ventricular pressure involved activation of calcium channel type-L, brought
      indirectly changes in the intracellular calcium levels and subsequently induced a
      positive inotropic effect.

PMID- 22159541
TI  - [Percentile values for physical condition for Cali, Colombian children and
      adolescents].
AB  - INTRODUCTION: Baseline data for physical condition are not available for
      adolescents in Cali, Colombia. OBJECTIVE: This study aimed to develop
      representative age- and sex- specific percentile baseline data for physical
      condition (mL.kg-1.min-1) for urban adolescents aged 10-16 years. Materials and
      methods. The sample (n=1,773) consisted of 865 males and 908 females from the
      cross-sectional population survey, the IFRECNTEC Study (Identification of Risk
      Factors of Non-Transmissible Adult Chronic Diseases in School-age Populations in
      the City of de Cali), for whom the data for physical condition were recorded.
      Smoothed age- and sex- specific 5th, 25th, 50th, 75th, 90th and 95th centile
      values where derived using least mean squares regression analysis. RESULTS:
      Percentile-based reference data for physical condition were presented for
      adolescent Colombian boys and girls for the first time. In males, the p50 of the
      PWC-170 (VO2max) ranged 49-43, and in females 52-40. A decreasing trend (~10%) in
      the p50 was seen in both sexes over 16 years of age. In general, more
      heterogeneity was present among males than females in terms of physical aptitude
      through VO2max test. CONCLUSION: The results established a baseline level of
      physical condition in adolescents that can be interpreted as an indicator of
      future cardiovascular health. They also recommend that the physical condition of
      Colombian adolescents must be improved to protect against cardiovascular disease
      in adulthood.

PMID- 22159542
TI  - [Profile of use of anti tumor necrosis factor in Colombian patients].
AB  - INTRODUCTION: Tumor necrosis factor-alpha antagonists (anti-TNFalpha) have shown
      an increasing consumption and generate a significant economic burden on health
      systems. OBJECTIVES: The prescribing patterns of tumor necrosis factor-alpha
      antagonists were determined in a patient population associated with the Sistema
      General de Seguridad Social en Salud in Colombia. MATERIALS AND METHODS: A
      descriptive observational study was conducted in 316 patients with respect to use
      of tumor necrosis factor-alpha antagonists during a treatment period from January
      2008 to June 2009. The database examined contained indications of use, inclusion
      criteria to medication, duration of illness, co-morbidities and adverse
      reactions. The data were retrieved from the clinical histories. Student's t test
      was used for the comparison of quantitative variables, and the chi-square test
      was used to establish associations between categorical variables and multivariate
      analysis were used. RESULTS: Mean age was 44.613.9 years; 63.9% of participants
      were female. Of the 316 patients, 17.1% received monotherapy. The order of
      prescription drugs was as follows: adalimumab (37.3%), infliximab (37.3%) and
      etanercept (25.4%), all were prescribed in appropriately defined daily doses. Co
      medication drugs most frequently prescribed were: disease-modifying anti
      rheumatic (82.9%), NSAIDs (29.1%), omeprazole (22.5%), antihypertensives (21.2%),
      folic acid (19.9%) calcium plus vitamin D (9.8%), calcitriol (6.0%). 10.4% of
      patients had a record of some adverse drug reaction. The average cost of therapy
      per patient per year was US$23,464. CONCLUSIONS: Anti-TNFalpha are being used at
      recommended doses, particularly in rheumatoid arthritis and in combination with
      other anti-rheumatic drugs. The direct cost of therapy was high for the country's
      health system.

PMID- 22159543
TI  - Utility of nitrate reductase assay for detection of multidrug-resistant
      Mycobacterium tuberculosis in a low resource setting.
AB  - Introduction. The performance of a drug susceptibility test may change when
      moving from the research stage to implementation on a population level in actual
      public health practice. Objective. The performance of a rapid drug susceptibility
      test was described for detecting multidrug-resistant Mycobacterium tuberculosis
      when implemented in the routine workflow of a low-resource reference laboratory.
      Materials and methods. A prospective study was done comparing the performance of
      the nitrate reductase assay with the conventional proportion method for
      rifampicin and isoniazid on 364 isolates were obtained from multidrug-resistant
      tuberculosis risk patients referred from diffrent Colombian laboratories.
      Results. When compared with the proportion method, the nitrate reductase assay
      sensitivity was 86.8% and 84.9% for rifampicin and isoniazid, respectively,
      whereas nitrate reductase assay specificity was 100% for isoniazid and
      rifampicin. Nitrate reductase assay sensitivity was significantly higher when the
      age of isolate was less than 70 days. A sensitivity of 94.4% dropped to 78.1% for
      rifampicin resistance for fresh and old isolates, respectively (Fisher exact
      test, p=0.05). For isoniazid resistance using fresh and old isolates, 94.7%
      vs.74.3% sensitivities, were achieved (chi square test, p=0.03). The proportion
      of nitrate reductase assay ambiguous results was significantly higher in
      multidrug-resistant than in non-multidrug-resistant isolates (17.6% vs. 4.0%, chi
      square test, p<0.005). Conclusions. The nitrate reductase assay demonstrated
      provided reliable results for antibiotic resistance. However, using old cultures
      leds to a higher proportion of false sensitive results; furthermore, the nitrate
      reductase assay capability to detect multidrug-resistant tuberculosis decreased
      due to a higher proportion of non-interpretable results.

PMID- 22159544
TI  - [New trap for the capture of triatomines in wild and peridomestic habitats].
AB  - INTRODUCTION: Wild triatomines have become increasingly important in the
      transmission of Chagas disease because of their frequent house entry behavior.
      Knowledge of their biology is limited, and few tools are available for their
      collection. These needs led to the design of a new trap for live triatomines.
      OBJECTIVES: The characteristics are described of a new bait trap designed for
      collecting triatomines. Trap usage and preliminary results are described for
      collections in several regional natural habitats in Colombia. MATERIALS AND
      METHODS: The trap houses a live animal as bait and provides a shelter for
      triatomines that are attracted by the bait. RESULTS: The trap was very effective
      for collecting Rhodnius prolixus, Triatoma dimidiata and Rhodnius pallescens in
      the natural habitats of each species. Triatomine density ranged widely in palm
      environments in each of two regions, and a relatively higher density in areas
      surrounding dwellings in the Andean region. CONCLUSIONS: The new trap for
      collecting triatomines proved successful in collecting live wild triatomines,
      using live bait native to the study areas. It is easy to transport and place, it
      is functions well in a variety of habitats, and it is more effective than other
      traps using live bait.

PMID- 22159545
TI  - Mechanisms of human natural resistance to HIV: a summary of ten years of research
      in the Colombian population.
AB  - The natural history of human immunodeficiency virus type-1 (HIV-1) infection is a
      complex and variable process that, similarly to other infections, has clearly
      demonstrated the existence of mechanisms of human natural resistance. The
      resistance either inhibits the establishment of infection or delays disease
      progression. When there is continuous exposure to infectious viral particles,
      several genetic and immunological mechanisms are essential to lead to resistance
      to HIV-1 infection/progression. The objective of this manuscript was to review
      the different mechanisms so far proposed to be responsible for HIV-1 resistance
      and to present the main results derived from 10 years of research in this area
      among Colombian subjects. In particular, this review focuses on determining the
      mechanisms involved in the protection of a group of individuals repeatedly
      exposed to the virus but who remained exempt of serological and clinical evidence
      of HIV-1 infection. Although the studies carried out in our research group
      corroborated the protective role of some of the previously proposed mechanisms of
      protection, ongoing research worldwide has made it clear that the phenomenon of
      human natural resistance depends on multiple factors with an important genetic
      influence, and only multicenter studies involving individuals with different
      genetic backgrounds may determine more universal mechanisms of resistance.
      Increasing our knowledge in this field will contribute to the development of
      novel preventive and therapeutic measures.

PMID- 22159546
TI  - [ILT3+/ILT4+ tolerogenic dendritic cells and their influence on allograft
      survival].
AB  - Dendritic cells, the most powerful antigen-presenting cells, are important for
      triggering of the immune responses to allo-antigens. However, they also play a
      fundamental role in the peripheral tolerance maintenance. Tolerance is enhanced
      by the presence on the dendritic cell surface of the inhibitor receptors ILT3 and
      ILT4. They recruit protein tyrosine-phosphatases to their ITIM domains and
      inhibit antigen-presenting cell activation, leading T cell hypo-responsivensess.
      Moreover, these receptors favor a bidirectional interaction with T-suppressor and
      T-regulator cells, generating an antigen-specific immunoregulator cascade, in
      which the dendritic cell behaves as a tolerogenic cell. In the current review,
      analysis is centered on the biology and behavior of the tolerogenic dendritic
      cells that express high levels of ILT3 and ILT4. Some molecular and genetics
      aspects of these receptors are discussed as well as their importance in the
      modulation of the allo-specific antigen immune response to transplants.

PMID- 22159547
TI  - A digital microfluidic method for multiplexed cell-based apoptosis assays.
AB  - Digital microfluidics (DMF), a fluid-handling technique in which picolitre
      microlitre droplets are manipulated electrostatically on an array of electrodes,
      has recently become popular for applications in chemistry and biology. DMF
      devices are reconfigurable, have no moving parts, and are compatible with
      conventional high-throughput screening infrastructure (e.g., multiwell plate
      readers). For these and other reasons, digital microfluidics has been touted as
      being a potentially useful new tool for applications in multiplexed screening.
      Here, we introduce the first digital microfluidic platform used to implement
      parallel-scale cell-based assays. A fluorogenic apoptosis assay for caspase-3
      activity was chosen as a model system because of the popularity of apoptosis as a
      target for anti-cancer drug discovery research. Dose-response profiles of caspase
      3 activity as a function of staurosporine concentration were generated using both
      the digital microfluidic method and conventional techniques (i.e., pipetting,
      aspiration, and 96-well plates.) As expected, the digital microfluidic method had
      a 33-fold reduction in reagent consumption relative to the conventional
      technique. Although both types of methods used the same detector (a benchtop
      multiwell plate reader), the data generated by the digital microfluidic method
      had lower detection limits and greater dynamic range because apoptotic cells were
      much less likely to de-laminate when exposed to droplet manipulation by DMF
      relative to pipetting/aspiration in multiwell plates. We propose that the
      techniques described here represent an important milestone in the development of
      digital microfluidics as a useful tool for parallel cell-based screening and
      other applications.

PMID- 22159548
TI  - Postoperative infections of the lumbar spine: presentation and management.
AB  - PURPOSE: Postoperative surgical site infections (SSI) are a frequent complication
      following posterior lumbar spinal surgery. In this manuscript we review
      strategies for prevention, diagnosis and treatment of SSI. METHODS: The
      literature was reviewed using the Pubmed database. RESULTS: We identified fifty
      nine relevant manuscripts almost exclusively composed of Level III and IV
      studies. CONCLUSIONS: Risk factors for SSI include: 1) factors related to the
      nature of the spinal pathology and the surgical procedure and 2) factors related
      to the systemic health of the patient. Staphylococcus aureus is the most common
      infectious organism in reported series. Proven methods to prevent SSI include
      prophylactic antibiotics, meticulous adherence to aseptic technique and frequent
      release of retractors to prevent myonecrosis. The presentation of SSI is varied
      depending on the virulence of the infectious organism. Frequently, increasing
      pain is the only presenting complaint and can lead to a delay in diagnosis.
      Magnetic resonance imaging and the use of C-reactive protein laboratory studies
      are useful to establish the diagnosis. Treatment of SSI is centered on surgical
      debridement of all necrotic tissue and obtaining intra-operative cultures to
      guide antibiotic therapy. We recommend the involvement of an infectious disease
      specialist and use of minimum serial bactericidal titers to monitor the efficacy
      of antibiotic treatment. In the most cases, SSI can be adequately treated while
      leaving spinal instrumentation in place. For severe SSI, repeat debridement,
      delayed closure and involvement of a plastic surgeon may be necessary.

PMID- 22159549
TI  - Wrist arthroscopy in children and adolescents: a single surgeon experience of
      thirty-four cases.
AB  - PURPOSE: The purpose of this study was to report our experience of wrist
      arthroscopy in children and adolescents with chronic wrist pain in a
      retrospective single surgeon series. Therefore, technical differences or
      obstacles compared to standard wrist arthroscopy in adults, and complications
      were highlighted. METHODS: A retrospective data review of all patients undergoing
      wrist arthroscopy between 2002 and 2011 was performed. The basic inclusion
      criteria was chronic, therapy refractory wrist pain for more than three months in
      children and adolescents aged 18 years and younger. In total, 34 arthroscopies in
      27 girls and six boys were reviewed. The mean age at time of arthroscopic
      exploration was 14.6 years (range, 9.8-17.9 years). RESULTS: A total of 28 wrists
      showed a triangular fibrocartilage complex (TFCC) tear (82.4%). In 26 of 34
      (76.5%) inspected wrist joints additional pathologies besides TFCC tears were
      documented. As a consequence, 14 arthroscopic TFCC resections, two arthroscopic
      TFCC repairs and seven open resection arthroplasties were performed. Other
      concomitant procedures (e.g., ulna shortening) were performed in 25 patients (26
      wrists) because of predisposing malformations. No intraoperative or postoperative
      complications related to the arthroscopies were observed. No relevant technical
      differences to wrist arthroscopy in adults were experienced apart from cases of
      major anatomical malformations. CONCLUSIONS: Wrist arthroscopy has been shown to
      be a safe procedure to detect and treat paediatric wrist disorders. Nevertheless,
      we believe that this procedure should only be carried out by well-trained,
      experienced hand surgeons.

PMID- 22159550
TI  - An ERP study on the processing of common fractions.
AB  - The aim of this study was to examine how adults processed common fractions with
      common numerators under two distinct conditions. Whereas participants were
      presented with only common fractions in a "simple" condition, a "complex"
      condition involved the random presentation of common fractions as well as decimal
      fractions. In both conditions, participants were required to assess whether
      various "target" fractions were larger than or smaller than a "standard" common
      fraction (1/5). Behavioral results indicated that under both conditions,
      participants mentally processed the fractions componentially in terms of their
      constituent parts rather than holistically in terms of the numerical value of the
      fraction as a whole. The data provided by the event-related potentials (ERPs)
      demonstrated electrophysiological correlates of the componential processing of
      common fractions in the simple condition, as reflected in the latency and
      amplitude of P3. However, in contrast to what the behavioral data showed, there
      was no strong electrophysiological evidence to indicate that common fractions
      were accessed componentially in the complex condition. In addition, the complex
      condition was linked to longer latency and more negative amplitude of N2 over the
      frontal scalp than the simple condition, which could be attributed to the fact
      that the comparison of fractions in the complex condition involved task switching
      and thus was more taxing on cognitive control than the simple condition.

PMID- 22159551
TI  - Butylated hydroxyanisole affects immunomodulation and promotes macrophage
      phagocytosis in normal BALB/c mice.
AB  - Butylated hydroxyanisole (BHA), a synthetic antioxidant, has been used in fat and
      fatty foods to prevent oxidative deterioration. However, the functions of BHA on
      immune responses in normal mice remain elusive. The aim of the present study was
      to investigate the effects of oral treatment of BHA on immune responses in normal
      mice in vivo. BALB/c mice received various treatments. Blood samples were
      collected and analyzed. Flow cytometry was used to determine the levels of the
      cell markers. Results showed that BHA did not significantly affect the weight of
      the animal body and spleen in normal mice. BHA promoted macrophage phagocytosis
      from peripheral blood mononuclear cells, but did not alter this process in the
      peritoneal cavity. Furthermore, BHA did not influence natural-killer cell
      cytotoxicity in normal mice. Notably, BHA promoted the levels of CD3 (T cells)
      and decreased the level of CD19 (B cells), but did not significantly affect the
      levels of CD11b (monocytes) and macrophages (Mac-3) in normal mice. Based on
      these observations it can be concluded that BHA promotes immune responses by
      increasing T cells and activating phagocytosis by macrophages in normal mice.
      However, the molecular mechanisms require further investigation.

PMID- 22159552
TI  - Two pathogenic NF1 gene mutations identified in DNA from a child with mild
      phenotype.

PMID- 22159553
TI  - Chiari V or Chiari II plus?

PMID- 22159554
TI  - Menstrual cycle and knee joint position sense in healthy female athletes.
AB  - PURPOSE: The aim of this study was to investigate the effect of menstrual cycle
      on knee joint position sense (JPS) in healthy female athletes. METHODS: Sixteen
      healthy female athletes participated in this study. Serum estrogen and
      progesterone levels were collected during the three phases of menstrual cycle.
      The knee JPS was also measured during the same phases using a system comprise of
      skin markers, digital photography, and AutoCAD software. Absolute angular errors
      were calculated as well as changes in hormone levels between the three phases.
      RESULTS: Serum estrogen concentration was significantly higher during the mid
      luteal (179.5 Pg/ml) and mid-follicular (125.6 Pg/ml) phases as compared with the
      early-follicular (menses) (22.8 Pg/ml) phase (P = 0.0001). Also serum
      progesterone concentration was significantly higher during the mid-luteal phase
      (7.35 Ng/ml) as compared with the menses (0.58 Ng/ml) and mid-follicular (0.5
      Ng/ml) phases (P = 0.0001). The greatest amount of mean (SD) value of absolute
      error was at menses (4.2 degrees ), and the least amount of it was at mid-luteal
      (2.5 degrees ) phase. Also, a significant difference was observed within three
      phases of menstrual cycle (P = 0.025). CONCLUSION: The result of this study
      suggests that healthy female athletes have different levels of knee JPS across a
      menstrual cycle. JPS accuracy decreases in menses, when circulating sex-hormones
      levels are low. Therefore, female athletes are at higher risk of injury at menses
      and improving their awareness regarding the knee injury risk factors can be a
      fundamental step toward preventing injuries. LEVEL OF EVIDENCE: Case series,
      Level IV.

PMID- 22159556
TI  - Emodin reverses gemcitabine resistance in pancreatic cancer cells via the
      mitochondrial apoptosis pathway in vitro.
AB  - Gemcitabine resistance is a common problem of pancreatic cancer chemotherapy, and
      how to reverse it plays an important role in the treatment of pancreatic cancer.
      This study investigated the effect of emodin on the gemcitabine-resistant
      pancreatic cancer cell line SW1990/Gem, and explored the potential mechanism of
      its action. SW1990/Gem was obtained by culture of the pancreatic cancer cell line
      SW1990 in vitro by intermittently increasing the concentration of gemcitabine in
      the culture medium for 10 months, observing the morphology using inverted
      microscopy. SW1990/Gem cells were pretreated with emodin (10 uM) for different
      periods followed by treatment with gemcitabine (20 uM) for 48 h; cell
      proliferation was tested by MTT assay. SW1990/Gem cells were treated by emodin
      with different concentrations for 48 h, cell apoptosis was detected by flow
      cytometry (FCM). The expression of gene and protein, such as MDR-1 (P-gp), NF
      kappaB, Bcl-2, Bax, cytochrome-C (cytosol), caspase-9 and -3 were measured by RT
      PCR and Western blotting. The function of P-gp in SW1990/Gem cells was checked by
      FCM. The results showed that the SW1990/Gem cells changed greatly in morphology
      and the resistance index was 48.63. Emodin promoted cell apoptosis of the
      gemcitabine-resistant cell line SW1990/Gem in a dose-dependent manner. Emodin
      enhanced the SW1990/Gem cell sensitivity to gemcitabine in a time-dependent
      manner. Emodin monotherapy or combination with gemcitabine both decreased the
      gene and protein expression levels of MDR-1 (P-gp), NF-kappaB and Bcl-2 and
      inhibited the function of P-gp, but increased the expression levels of Bax,
      cytochrome-C (cytosol), caspase-9 and -3, and promoted cell apoptosis. This
      demonstrated that emodin had a reversing effect on the gemcitabine-resistant cell
      line SW1990/Gem, possibly via decreasing the function of P-gp and activating the
      mitochondrial apoptosis pathway in vitro.

PMID- 22159557
TI  - Development of the first sphingomyelin biomimetic stationary phase for
      immobilized artificial membrane (IAM) chromatography.
AB  - A prototype sphingomyelin stationary phase for Immobilized Artificial Membrane
      (IAM) chromatography was synthesized by an ultra-short, solid-phase inspired
      methodology, in which an oxidative release monitoring strategy played a vital
      role. Evaluated in a proof-of-concept model for blood-brain barrier passage,
      partial least squares regression demonstrated its potential as an in vitro
      prediction tool.

PMID- 22159558
TI  - SNX3-dependent regulation of epidermal growth factor receptor (EGFR) trafficking
      and degradation by aspirin in epidermoid carcinoma (A-431) cells.
AB  - Since being introduced globally as aspirin in 1899, acetylsalicylic acid has been
      widely used as an analgesic, anti-inflammation, anti-pyretic, and anti-thrombotic
      drug for years. Aspirin had been reported to down-regulate surface expression of
      CD40, CD80, CD86, and MHCII in myeloid dendritic cells (DC), which played
      essential roles in regulating the immune system. We hypothesized that the down
      regulation of these surface membrane proteins is partly due to the ability of
      aspirin in regulating trafficking/sorting of endocytosed surface membrane
      proteins. By using an established epidermoid carcinoma cell line (A-431), which
      overexpresses the epidermal growth factor receptor (EGFR) and transferrin
      receptor (TfnR), we show that aspirin (1) reduces cell surface expression of EGFR
      and (2) accumulates endocytosed-EGFR and -TfnR in the early/sorting endosome
      (ESE). Further elucidation of the mechanism suggests that aspirin enhances
      recruitment of SNX3 and SNX5 to membranes and consistently, both SNX3 and SNX5
      play essential roles in the aspirin-mediated accumulation of endocytosed-TfnR at
      the ESE. This study sheds light on how aspirin may down-regulate surface
      expression of EGFR by inhibiting/delaying the exit of endocytosed-EGFR from the
      ESE and recycling of endocytosed-EGFR back to the cell surface.

PMID- 22159559
TI  - Morphological and functional characterization of leech circulating blood cells:
      role in immunity and neural repair.
AB  - Unlike most invertebrates, annelids possess a closed vascular system distinct
      from the coelomic liquid. The morphology and the function of leech blood cells
      are reported here. We have demonstrated the presence of a unique cell type which
      participates in various immune processes. In contrast to the mammalian spinal
      cord, the leech CNS is able to regenerate and restore function after injury. The
      close contact of the blood with the nerve cord also led us to explore the
      participation of blood in neural repair. Our data evidenced that, in addition to
      exerting peripheral immune functions, leech blood optimizes CNS neural repair
      through the release of neurotrophic substances. Circulating blood cells also
      appeared able to infiltrate the injured CNS where, in conjunction with microglia,
      they limit the formation of a scar. In mammals, CNS injury leads to the
      generation of a glial scar that blocks the mechanism of regeneration by
      preventing axonal regrowth. The results presented here constitute the first
      description of neuroimmune functions of invertebrate blood cells. Understanding
      the basic function of the peripheral circulating cells and their interactions
      with lesioned CNS in the leech would allow us to acquire insights into the
      complexity of the neuroimmune response of the injured mammalian brain.

PMID- 22159560
TI  - The interplay between posture control and memory for spatial locations.
AB  - Three experiments examined interactions between posture control in upright stance
      and a concurrent location memory task. Healthy young participants stood upright
      and memorized the locations of dots presented on a computer screen. In the
      retrieval phase, they indicated whether arrows presented on the screen would pass
      through any of the memorized locations. Postural sway variability was measured
      either during the retention period or during retrieval. Relative to not
      performing the memory task, postural sway variability increased in the retention
      period when the eyes were closed, but remained unaffected when the eyes were
      open. During retrieval, postural sway variability was reduced relative to the no
      memory-task condition. Results were interpreted in terms of dual-task costs
      associated with maintaining multiple frames of reference.

PMID- 22159561
TI  - The prevalence of urinary incontinence in American Indian women from a South
      Dakota tribe.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this pilot study was to evaluate the
      prevalence and associated risk factors for urinary incontinence in a Northern
      Plains tribe of American Indian women. METHODS: The Urogenital Distress Inventory
      Short Form was used to assess urinary incontinence in a sample of American Indian
      women from one tribe. This was a cross-sectional convenience sampling of 234
      eligible participants. Participant's ages ranged from 18 to 80 years. Stata/Se
      9.1 software was used in statistical analysis. RESULTS: The overall prevalence of
      urinary stress incontinence was 15.4%, urgency incontinence 2.14%, and mixed
      incontinence 20.5%. Both stress and urgency incontinence was found to be low in
      this sample population. CONCLUSIONS: A reduced prevalence of stress and urgency
      incontinence is seen in our sample. Our study group showed a high prevalence of
      known risk factors associated with urinary incontinence. We intend to extend our
      study for further understanding of this patient population.

PMID- 22159563
TI  - Repeatability of post-void residual urine >= 100 ml in urogynaecologic patients.
AB  - INTRODUCTION AND HYPOTHESIS: Post-void residual urine (PVR) is a key variable in
      the assessment of the emptying function of the lower urinary tract and is often
      used as an outcome measure after treatment. Increased PVR can lead to further
      investigation and treatment, or cancellation of planned incontinence surgery. In
      a prospective study, we aimed to assess the repeatability of the finding of PVR
      >= 100 ml in urogynaecologic patients. METHODS: Of 396 women with urogynaecologic
      complaints visiting our outpatient clinic, 297 had PVR measured after a
      micturition in full privacy preceded by normal desire to void. Women with PVR >=
      100 ml were offered a second and eventually a third PVR measurement after a
      subsequent micturition. A Verathon Bladder Scanner BV 9400 was used to measure
      PVR immediately after micturition. RESULTS: The prevalence of PVR >= 100 was 14%,
      which declined to 1.3% on repeated measurements. Voided volumes did not vary
      between voids. CONCLUSIONS: One PVR measurement >= 100 ml is unreliable and needs
      repetition to confirm consistency.

PMID- 22159564
TI  - Haemostatic variables during normal menstrual cycle. A systematic review.
AB  - For a number of haemostatic factors menstrual cycle variation has been studied.
      Such variation could have clinical implications for the timing of haemostatic
      testing in women. It was our objective to systematically review the literature
      about evidence for timing of haemostatic testing during menstrual cycle.We
      searched MEDLINE, EMBASE and the Cochrane library to identify studies that
      measured haemostatic variables [platelet function, von Willebrand factor (VWF),
      factor VIII (FVIII), factor IX (FIX), factor XI (FXI), factor XIII (FXIII), D
      dimer, plasminogen activator inhibitor-I (PAI-I), tissue plasminogen activator
      (tPA), urokinase-type plasminogen activator (uPA), alpha2-antiplasmin and
      fibrinogen] during normal menstrual cycle without hormonal contraceptives. Two
      investigators independently selected studies, and abstracted data in duplicate.
      We identified 1,046 studies of which we included 30 studies (25 longitudinal and
      5 cross-sectional studies). All studies reported on haemostatic variables during
      menstrual cycle. Overall, most of the studies found no cyclic variation in VWF,
      FVIII, FXI, FXIII, fibrinolytic factors (PAI, t-PA, uPA, D-dimer and alpha2
      antiplasmin) and fibrinogen. However, in studies where these variables showed any
      variation, they reached the lowest levels during menstrual and early follicular
      phase, especially for VWF, FVIII and platelet function tests. In conclusion, the
      optimal timing for haemostatic testing during menstrual cycle seems to be
      menstrual and early follicular phase.

PMID- 22159565
TI  - Acoustic analysis of the alarm call of the Anatolian ground squirrel Spermophilus
      xanthoprymnus: a description and comparison with alarm calls of the Taurus S.
      taurensis and European S. citellus ground squirrels.
AB  - The Anatolian ground squirrel Spermophilus xanthoprymnus like other ground
      dwelling sciurids, emits alarm calls in the presence of predators. In this study,
      we provide a description of the acoustic structure of alarm call of this species
      and compare it to those of two closely related species, the Taurus ground
      squirrel Spermophilus taurensis and the European ground squirrel Spermophilus
      citellus. The alarm call of S. xanthoprymnus is a tonal sound mostly consisting
      of two different elements-the first element has low frequency modulation while
      the second element is highly frequency modulated. A similar basic structure can
      be found in the alarm calls of some other old world ground squirrel species of
      the genus Spermophilus, including S. taurensis and S. citellus. Despite this
      similarity, we found that these three species can be clearly distinguished on the
      basis of their alarm calls. Differences in the acoustic structure of S.
      xanthoprymnus and S. taurensis calls are especially remarkable, as these two
      species were considered to be conspecific until 2007. S. xanthoprymnus and S.
      taurensis were also demonstrated to have closer acoustic similarity, which is in
      contrast to results based on molecular data indicating that S. taurensis is most
      closely related to S. citellus.

PMID- 22159566
TI  - Naturwissenschaften: recent advances, changes and challenges.

PMID- 22159568
TI  - Palladium-catalyzed synthesis of terminal acetals via highly selective anti
      Markovnikov nucleophilic attack of pinacol on vinylarenes, allyl ethers, and 1,5
      dienes.
AB  - A palladium-catalyzed reaction of vinylarenes, allyl ethers, and 1,5-dienes with
      pinacol proceeded via a selective anti-Markovnikov nucleophilic attack to afford
      corresponding terminal acetals as major products. The bulkiness of pinacol was
      found to be critical in controlling the regioselectivity.

PMID- 22159569
TI  - A phase II study of docetaxel weekly in combination with carboplatin every three
      weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer:
      neurological toxicity and quality-of-life evaluation.
AB  - The purpose of this study was to assess the response rate, toxicity, progression
      free survival (PFS) and overall survival (OS) in a series of advanced stage
      ovarian carcinoma patients treated with a first-line weekly docetaxel and three
      weekly carboplatin regimens. All eligible patients were treated with intravenous
      docetaxel (30 mg/m2) on Days 1, 8 and 15, and carboplatin (area under the curve,
      5) on Day 1; Q21 days for at least 6 cycles. Neurological tests, questionnaires,
      and the EORTC QLQ-C30 and OV28 were used for quality-of-life assessments. One
      hundred and six patients received at least one cycle of primary chemotherapy
      (median 6.0; range, 1-9) and they were evaluable for toxicity assessment. Eighty
      five patients had evaluable disease and received at least 3 courses of
      chemotherapy and were evaluable for clinical response rate. The overall response
      rate was 78.8% (95% CI 70.1-87.5%) and the biochemical response was 92.8% (95% CI
      87.2-98.4%). The median PFS was 12.0 months and the median OS was 35.3 months.
      Thirty-six patients (34.0%) experienced grades 3 and 4 neutropenia, which
      resulted in the removal of 3 patients. Six patients (5.7%) experienced grades 3
      or 4 thrombocytopenia. No patients experienced grade 3-4 sensory neuropathy.
      Epiphora, nail changes and fatigue were frequently recorded non-hematological
      side effects. The tolerable hematological toxicity (no need for colony
      stimulating factors) and the low rate of severe neurotoxicity (only grade 1-2)
      and response rates in line with the standard 3-week paclitaxel-carboplatin
      regimen for advanced primary ovarian carcinoma after suboptimal cytoreductive
      surgery make this regimen an interesting alternative in selected patients.

PMID- 22159570
TI  - Reliability of CARD-FISH procedure for enumeration of Archaea in deep-sea
      surficial sediments.
AB  - The enumeration of Archaea in deep-sea sediment samples is still limited,
      although different methodological procedures have been applied. Among these,
      catalysed reporter deposition-fluorescence in situ hybridisation (CARD-FISH)
      technique is a promising tool for estimation of archaeal abundance in deep-sea
      sediment samples. Comparing different permeabilisation treatments, the best
      results obtained both on archaeal pure cultures and on natural assemblages were
      with hydrochloric acid (0.1 M) and proteinase K (0.004 U/ml) treatments. The
      application of CARD-FISH on deep-sea sediments revealed that Archaea reach up to
      41% of total prokaryotic cells. Specific probes for planktonic Archaea showed
      that marine Crenarchaea dominated archaeal seafloor communities. No clear
      bathymetric trends were observed for archaeal abundances and the morphology of
      continental margin (slope vs. canyon) seems not to have a direct influence on
      archaeal relative abundances. The site-specific sediment habitat-both abiotic
      environmental setting and sedimentary organic matter quality-explain up to 65% of
      variance of archaeal, crenarchaeal and euryarchaeal relative abundance,
      suggesting a wide ecophysiological adaptation to deep-sea benthic ecosystems. The
      findings demonstrate that Archaea are an important component of benthic microbial
      assemblages so far neglected, and hence they lay the groundwork for more focused
      research on their ecological importance in the functioning of deep-sea benthic
      ecosystems.

PMID- 22159571
TI  - Infections after spinal correction and fusion for spinal deformities in childhood
      and adolescence.
AB  - BACKGROUND: Infection after spinal fusion for scoliosis is a commonly reported
      complication. Although techniques in paediatric spinal fusion have improved with
      regard to infection prophylaxis, postoperative infection rates range from 0.4% to
      8.7%. INFECTION RATES AND CAUSATIVE FACTORS: The rate of infection in surgery for
      adolescent idiopathic scoliosis (AIS) has ranged from 0.9% to 3%. The rate of
      infection in spinal surgery for deformity related to myelomeningocele has been
      reported to be from 8% to 24%. The rate of infection in spinal surgery for
      deformity related to cerebral palsy has been reported to be from 6.1% to 8.7%.
      Infection after spinal fusion for scoliosis related to a muscular dystrophy is
      generally less frequent. Despite a large number of cases and studies, the
      literature did not provide documentation of several factors that may be related
      to the occurrence of wound infection. The rate of wound infection after spine
      surgery is dependent on many factors, including the complexity of the procedure,
      health status of the patient, and potentially the experience and technique of the
      operating surgeon. TREATMENT ALGORITHM: The general algorithm for treatment
      depends on a variety of factors, including the delay from the index procedure,
      the infecting organism, the location and extent of the infection, the gross
      appearance of the fusion mass, and the surgical strategy used to correct the
      initial deformity. For infections that develop within the first 90 days after the
      index procedure all attempts to retain the instrumentation should be made. In
      late infections, the fusion mass must be carefully inspected before
      instrumentation removal is considered. Although fusion may appear to be solid
      both radiographically and intra-operatively, there still may be the possibility
      of loss of correction at last follow-up. CONCLUSION: Deep wound infection after
      instrumented fusion of the spine remains a difficult and challenging clinical
      problem and entails substantial morbidity, cost, and recovery time for the
      patient. An aggressive approach to deep wound infection emphasising early
      irrigation and debridement allowed preservation of instrumentation and successful
      fusion in most cases. At the conclusion of treatment, patients can expect a
      medium-term clinical outcome similar to patients in whom infectious complication
      did not occur.

PMID- 22159572
TI  - Differential blood lipid-lowering effects of alkylsulfonated chitosan of
      different molecular weights in Syrian hamsters in vivo.
AB  - This study investigated the effects of alkylsulfonated chitosan of different
      molecular weights on intestinal lipid absorption, blood lipid profiles and
      circulating adhesion molecules. Syrian hamsters were fed an AIN-93G-based high
      fat diet (HFD) and were orally administered 5 or 10 mg/kg BW of oligomer (6 kDa)
      chitosan (OC), low-molecular-weight (70 kDa) chitosan (LMC) or high-molecular
      weight (200 kDa) chitosan (HMC) four times per week for 12 weeks. Animals
      receiving 2.5 mg/kg BW lovastatin (LOVA) served as a positive control. The blood
      lipid profiles of these control animals revealed that all chitosans and LOVA
      significantly decreased total triglyceride, total cholesterol, low-density
      lipoprotein (LDL)-cholesterol and very-low-density lipoprotein (VLDL)-cholesterol
      levels in a dose-dependent manner compared to the HFD-fed controls (P<0.05). The
      blood lipid lowering effectiveness of the three chitosans followed the order of
      LMC>OC>HMC. Hamsters receiving 5 and 10 mg/kg LMC (P<0.05) exhibited an increase
      in fecal fat content. Immunoblot assay revealed that acyl-coenzyme A:cholesterol
      acyltransferase-2 (ACAT-2) expression was suppressed in all chitosan-fed animals
      compared to the HFD-fed controls (P<0.05). These results suggest that chitosan
      effectively decreases blood lipid content, and its effectiveness depends on the
      molecular size of chitosan. The hypolipidemic effect of chitosan is partly
      attributed to its suppression of intestinal lipid absorption and hepatic ACAT-2
      expression.

PMID- 22159574
TI  - Electronic tuning of chiral diene ligands in iridium-catalyzed asymmetric 1,6
      addition of arylboroxines to delta-aryl-alpha,beta,gamma,delta-unsaturated
      ketones.
AB  - Asymmetric addition of arylboroxines to delta-aryl-alpha,beta,gamma,delta
      unsaturated ketones proceeded in the presence of an iridium catalyst coordinated
      with a chiral diene ligand to give high yields of delta-diaryl ketones with very
      high enantioselectivity.

PMID- 22159573
TI  - Protein profiling of microdomains purified from renal cell carcinoma and normal
      kidney tissue samples.
AB  - Renal cell carcinoma (RCC) is representing about 3% of all adult cancers. A
      promising strategy for cancer biomarker discovery is subcellular comparative
      proteomics, allowing enriching specific cell compartments and assessing
      differences in protein expression patterns. We investigated the proteomic profile
      of a peculiar RCC subcellular compartment, plasma membrane microdomains (MD),
      involved in cell signalling, transport, proliferation and in many human diseases,
      such as cancer. Subcellular fractions were prepared by differential
      centrifugation from surgical samples of RCC and adjacent normal kidney (ANK). MD
      were isolated from plasma-membrane-enriched fractions after Triton X-100
      treatment and sucrose density gradient ultracentrifugation. MD derived from RCC
      and ANK tissues were analyzed after SDS-PAGE separation by LC-ESI-MS/MS. We
      identified 93 proteins from MD isolated from RCC tissue, and 98 proteins from ANK
      MD. About 70% of the identified proteins are membrane-associated and about half
      of these are known as microdomain-associated. GRAVY scores assignment shows that
      most identified proteins (about 70%) are in the hydrophobic range. We chose a
      panel of proteins to validate their differential expression by WB. In conclusion,
      our work shows that RCC microdomain proteome is reproducibly different from ANK,
      and suggests that mining into such differences may support new biomarker
      discovery.

PMID- 22159575
TI  - Role of COX-2 activity and CRP levels in patients with non-melanoma skin cancer. 
      765G>C PTGS2 polymorphism and NMSC risk.
AB  - Non-melanoma skin cancer is one of the most common of all cancers and the
      incidence has increased in the last years as a result of many factors including
      increased tanning, life style and possible global climate change. Inflammation
      plays an important role in cancer development and is frequently evaluated by
      serum C-reactive protein (CRP) levels. PTGS2 -765C allele coding for COX-2 has
      been found to be associated with lower plasma levels of CRP. The objectives of
      this study are: evaluation of the association between PTGS2 -765G>C polymorphism
      and the occurrence of non-melanoma skin cancer, the relationship between this
      polymorphism and cyclooxygenase-2 activity in skin tissue, as well as the
      correlation with serum CRP levels in patients with non-melanoma skin cancer. We
      used PCR-RFLP technique to explore -765G>C PTGS2 gene polymorphism, colorimetric
      analysis for cyclooxygenase-2 activity in skin tissue and immunoturbidimetric
      assay for CRP serum levels in 174 patients with non-melanoma skin cancer [54
      patients with basal cell carcinoma (BCC) and 120 patients with squamous cell
      carcinoma (SCC)] and 80 healthy subjects. PTGS2 -765G>C polymorphism failed to
      show an association with non-melanoma skin cancer risk. We observed a significant
      increase in COX-2 activity in SCC and BCC patients compared to control tissue
      (0.58 +/- 0.11 and 0.63 +/- 0.09 U/mg protein, respectively vs. 0.16 +/- 0.01
      U/mg protein). BCC and SCC intra-group analysis showed lower COX-2 activity in C
      allele carriers versus non-carriers (p < 0.001 and p < 0.0001, respectively). In
      BCC and SCC patients with GG genotype, CRP level is significantly increased
      compared to control group (p < 0.0001 and p < 0.0001, respectively). Intra-group
      comparison of CRP levels showed significantly lower CRP levels in patients
      carrying C-allele compared to GG homozygotes in BCC (p = 0.0001) and SCC patients
      (p < 0.0001). PTGS2 -765G>C polymorphism failed to show an association with non
      melanoma skin cancer risk. Regarding prognostic indicators, no consistent
      association emerged between PTGS2 -765G>C polymorphism and COX-2 activity or CRP
      levels.

PMID- 22159576
TI  - Pediatric risk of malignancy index for preoperative evaluation of childhood
      ovarian tumors.
AB  - PURPOSE: This study aimed to develop and provisionally validate a novel scoring
      index for preoperative cancer-risk prediction in childhood ovarian tumors.
      METHODS: Fifty-five girls aged 18 and below underwent surgery for ovarian masses
      between 2004 and 2009. Benign or non-benign histological diagnoses (the latter
      including all malignant and borderline tumors and tumors containing immature
      components) were correlated with clinical and biochemical parameters, and blinded
      scores of ultrasound and computed-tomography using multivariate logistic
      regression. Regression coefficients were used as weighting factors to create an
      additive index. This index was validated prospectively against 23 consecutive
      adnexal masses operated in 2010. RESULTS: In total, 67 tumors were benign and 11
      non-benign. Non-benign diagnosis was independently associated with the maximum
      diameter of the largest solid component (score = value in cm), the presence of
      sex hormone-related symptoms (score = +6), and enhancement or flow in a septum or
      solid papillary projection (score = +4). The novel scoring index was calculated
      as the total score of these three parameters. A cutoff score of 7 gave a
      specificity of 97.9% and sensitivity of 87.5% for the training data set, and
      specificity and sensitivity of 100% for the pilot testing set. CONCLUSION: The
      novel pediatric risk-of-malignancy index is able to accurately discriminate
      between benign and non-benign ovarian tumors in children and adolescents. Its
      preoperative application may guide surgical management decisions before the
      availability of histological confirmation.

PMID- 22159577
TI  - Infectious complications in the management of gastroschisis.
AB  - BACKGROUND/PURPOSE: Neonates with gastroschisis make up an increasing proportion
      of prolonged surgical NICU admissions. While infectious complications are known
      to increase patient morbidity, it is unclear whether they vary according to
      abdominal closure method, or can be predicted by initial patient assessment.
      METHODS: A national, prospective, disease-specific database was evaluated for
      episodes of wound infection (WI) and catheter-related infection (CRI). Antibiotic
      use and timing, as well as method and location of abdominal closure were studied.
      The gastroschisis prognostic score (GPS) was calculated and evaluated as a
      predictor of infectious complications. RESULTS: Of 395 patients, 48 (12.6%) had a
      documented abdominal WI, and 59 patients (14.9%) had at least one episode of CRI
      most commonly coagulase negative staphylococcus. Most abdominal closures took
      place within 6 h of admission (194 = 51.3%), while 132 (34.9%) were delayed
      greater than 24 h. The WI rate was greater in the delayed group (21.2 vs. 8.2%, p
      = 0.0006). The GPS was found to predict development of an infectious complication
      (WI + CRI, p = 0.04). CONCLUSION: Infectious complications remain an important
      consideration in the management of gastroschisis. GPS correlates with the
      development of infectious complications. Prophylaxis for skin flora and early
      closure, when feasible, may reduce WI rates.

PMID- 22159578
TI  - Canonical BMP7 activity is required for the generation of discrete neuronal
      populations in the dorsal spinal cord.
AB  - BMP activity is essential for many steps of neural development, including the
      initial role in neural induction and the control of progenitor identities along
      the dorsal-ventral axis of the neural tube. Taking advantage of chick in ovo
      electroporation, we show a novel role for BMP7 at the time of neurogenesis
      initiation in the spinal cord. Using in vivo loss-of-function experiments, we
      show that BMP7 activity is required for the generation of three discrete
      subpopulations of dorsal interneurons: dI1-dI3-dI5. Analysis of the BMP7 mouse
      mutant shows the conservation of this activity in mammals. Furthermore, this BMP7
      activity appears to be mediated by the canonical Smad pathway, as we demonstrate
      that Smad1 and Smad5 activities are similarly required for the generation of dI1
      dI3-dI5. Moreover, we show that this role is independent of the patterned
      expression of progenitor proteins in the dorsal spinal cord, but depends on the
      BMP/Smad regulation of specific proneural proteins, thus narrowing this BMP7
      activity to the time of neurogenesis. Together, these data establish a novel role
      for BMP7 in primary neurogenesis, the process by which a neural progenitor exits
      the cell cycle and enters the terminal differentiation pathway.

PMID- 22159579
TI  - Nervous systems of the sea anemone Nematostella vectensis are generated by
      ectoderm and endoderm and shaped by distinct mechanisms.
AB  - As a sister group to Bilateria, Cnidaria is important for understanding early
      nervous system evolution. Here we examine neural development in the anthozoan
      cnidarian Nematostella vectensis in order to better understand whether similar
      developmental mechanisms are utilized to establish the strikingly different
      overall organization of bilaterian and cnidarian nervous systems. We generated a
      neuron-specific transgenic NvElav1 reporter line of N. vectensis and used it in
      combination with immunohistochemistry against neuropeptides, in situ
      hybridization and confocal microscopy to analyze nervous system formation in this
      cnidarian model organism in detail. We show that the development of neurons
      commences in the ectoderm during gastrulation and involves interkinetic nuclear
      migration. Transplantation experiments reveal that sensory and ganglion cells are
      autonomously generated by the ectoderm. In contrast to bilaterians, neurons are
      also generated throughout the endoderm during planula stages. Morpholino-mediated
      gene knockdown shows that the development of a subset of ectodermal neurons
      requires NvElav1, the ortholog to bilaterian neural elav1 genes. The orientation
      of ectodermal neurites changes during planula development from longitudinal (in
      early-born neurons) to transverse (in late-born neurons), whereas endodermal
      neurites can grow in both orientations at any stage. Our findings imply that
      elav1-dependent ectodermal neurogenesis evolved prior to the divergence of
      Cnidaria and Bilateria. Moreover, they suggest that, in contrast to bilaterians,
      almost the entire ectoderm and endoderm of the body column of Nematostella
      planulae have neurogenic potential and that the establishment of connectivity in
      its seemingly simple nervous system involves multiple neurite guidance systems.

PMID- 22159580
TI  - The kinase Sgg modulates temporal development of macrochaetes in Drosophila by
      phosphorylation of Scute and Pannier.
AB  - Evolution of novel structures is often made possible by changes in the timing or
      spatial expression of genes regulating development. Macrochaetes, large sensory
      bristles arranged into species-specific stereotypical patterns, are an
      evolutionary novelty of cyclorraphous flies and are associated with changes in
      both the temporal and spatial expression of the proneural genes achaete (ac) and
      scute (sc). Changes in spatial expression are associated with the evolution of
      cis-regulatory sequences, but it is not known how temporal regulation is
      achieved. One factor required for ac-sc expression, the expression of which
      coincides temporally with that of ac-sc in the notum, is Wingless (Wg; also known
      as Wnt). Wingless downregulates the activity of the serine/threonine kinase
      Shaggy (Sgg; also known as GSK-3). We demonstrate that Scute is phosphorylated by
      Sgg on a serine residue and that mutation of this residue results in a form of Sc
      with heightened proneural activity that can rescue the loss of bristles
      characteristic of wg mutants. We suggest that the phosphorylated form of Sc has
      reduced transcriptional activity such that sc is unable to autoregulate, an
      essential function for the segregation of bristle precursors. Sgg also
      phosphorylates Pannier, a transcriptional activator of ac-sc, the activity of
      which is similarly dampened when in the phosphorylated state. Furthermore, we
      show that Wg signalling does not act directly via a cis-regulatory element of the
      ac-sc genes. We suggest that temporal control of ac-sc activity in cyclorraphous
      flies is likely to be regulated by permissive factors and might therefore not be
      encoded at the level of ac-sc gene sequences.

PMID- 22159582
TI  - Balancing of ephrin/Eph forward and reverse signaling as the driving force of
      adaptive topographic mapping.
AB  - The retinotectal projection, which topographically maps retinal axons onto the
      tectum of the midbrain, is an ideal model system with which to investigate the
      molecular genetics of embryonic brain wiring. Corroborating Sperry's seminal
      hypothesis, ephrin/Eph counter-gradients on both retina and tectum were found to
      represent matching chemospecificity markers. Intriguingly, however, it has never
      been possible to reconstitute topographically appropriate fiber growth in vitro
      with these cues. Moreover, experimentally derived molecular mechanisms have
      failed to provide explanations as to why the mapping adapts to grossly diverse
      targets in some experiments, while displaying strict point-to-point specificity
      in others. In vitro, ephrin-A/EphA forward, as well as reverse, signaling mediate
      differential repulsion to retinal fibers, instead of providing topographic
      guidance. We argue that those responses are indicative of ephrin-A and EphA being
      members of a guidance system that requires two counteracting cues per axis.
      Experimentally, we demonstrate by introducing novel double-cue stripe assays that
      the simultaneous presence of both cues indeed suffices to elicit topographically
      appropriate guidance. The peculiar mechanism, which uses forward and reverse
      signaling through a single receptor/ligand combination, entails fiber/fiber
      interactions. We therefore propose to extend Sperry's model to include ephrin
      A/EphA-based fiber/fiber chemospecificity, eventually out-competing fiber/target
      interactions. By computational simulation, we show that our model is consistent
      with stripe assay results. More importantly, however, it not only accounts for
      classical in vivo evidence of point-to-point and adaptive topographic mapping,
      but also for the map duplication found in retinal EphA knock-in mice.
      Nonetheless, it is based on a single constraint of topographic growth cone
      navigation: the balancing of ephrin-A/EphA forward and reverse signaling.

PMID- 22159581
TI  - Transmembrane voltage potential controls embryonic eye patterning in Xenopus
      laevis.
AB  - Uncovering the molecular mechanisms of eye development is crucial for
      understanding the embryonic morphogenesis of complex structures, as well as for
      the establishment of novel biomedical approaches to address birth defects and
      injuries of the visual system. Here, we characterize change in transmembrane
      voltage potential (V(mem)) as a novel biophysical signal for eye induction in
      Xenopus laevis. During normal embryogenesis, a striking hyperpolarization
      demarcates a specific cluster of cells in the anterior neural field. Depolarizing
      the dorsal lineages in which these cells reside results in malformed eyes.
      Manipulating V(mem) of non-eye cells induces well-formed ectopic eyes that are
      morphologically and histologically similar to endogenous eyes. Remarkably, such
      ectopic eyes can be induced far outside the anterior neural field. A Ca(2+)
      channel-dependent pathway transduces the V(mem) signal and regulates patterning
      of eye field transcription factors. These data reveal a new, instructive role for
      membrane voltage during embryogenesis and demonstrate that V(mem) is a crucial
      upstream signal in eye development. Learning to control bioelectric initiators of
      organogenesis offers significant insight into birth defects that affect the eye
      and might have significant implications for regenerative approaches to ocular
      diseases.

PMID- 22159583
TI  - Light-dependent phosphorylation of the carboxy tail of mouse melanopsin.
AB  - Melanopsin-based phototransduction is involved in non-image forming light
      responses including circadian entrainment, pupil constriction, suppression of
      pineal melatonin synthesis, and direct photic regulation of sleep in vertebrates.
      Given that the functions of melanopsin involve the measurement and summation of
      total environmental luminance, there would appear to be no need for the rapid
      deactivation typical of other G-protein coupled receptors. In this study,
      however, we demonstrate that heterologously expressed mouse melanopsin is
      phosphorylated in a light-dependent manner, and that this phosphorylation is
      involved in regulating the rate of G-protein activation and the lifetime of
      melanopsin's active state. Furthermore, we provide evidence for light-dependent
      phosphorylation of melanopsin in the mouse retina using an in situ proximity
      ligation assay. Finally, we demonstrate that melanopsin preferentially interacts
      with the GRK2/3 family of G-protein coupled receptor kinases through co
      immunoprecipitation assays. Based on the complement of G-protein receptor kinases
      present in the melanopsin-expressing retinal ganglion cells, GRK2 emerges as the
      best candidate for melanopsin's cognate GRK.

PMID- 22159584
TI  - CHFR: a key checkpoint component implicated in a wide range of cancers.
AB  - CHFR (Checkpoint with Forkhead-associated and RING finger domains) has been
      implicated in a checkpoint regulating entry into mitosis. However, the details
      underlying its roles and regulation are unclear due to conflicting lines of
      evidence supporting different notions of its functions. We provide here an
      overview of how CHFR is thought to contribute towards regulating mitotic entry
      and present possible explanations for contradictory observations published on the
      functions and regulation of CHFR. Furthermore, we survey key data showing
      correlations between promoter hypermethylation or down-regulation of CHFR and
      cancers, with a view on the likely reasons why different extents of correlations
      have been reported. Lastly, we explore the possibilities of exploiting CHFR
      promoter hypermethylation status in diagnostics and therapeutics for cancer
      patients. With keen interest currently focused on the association between
      hypermethylation of CHFR and cancers, details of how CHFR functions require
      further study to reveal how its absence might possibly contribute to
      tumorigenesis.

PMID- 22159585
TI  - Annexins as organizers of cholesterol- and sphingomyelin-enriched membrane
      microdomains in Niemann-Pick type C disease.
AB  - Growing evidence suggests that membrane microdomains enriched in cholesterol and
      sphingomyelin are sites for numerous cellular processes, including signaling,
      vesicular transport, interaction with pathogens, and viral infection, etc.
      Recently some members of the annexin family of conserved calcium and membrane
      binding proteins  have been recognized as cholesterol-interacting molecules and
      suggested to play a role in the formation, stabilization, and dynamics of
      membrane microdomains  to affect membrane lateral organization and to attract
      other proteins and signaling molecules onto their territory. Furthermore,
      annexins were implicated in the interactions between cytosolic and membrane
      molecules, in the turnover and storage of cholesterol  and in various signaling
      pathways. In this review, we focus on the mechanisms of interaction of annexins
      with lipid microdomains and the role of annexins in membrane microdomains
      dynamics including possible participation of the domain-associated forms of
      annexins in the etiology of human lysosomal storage disease called Niemann-Pick
      type C disease, related to the abnormal storage of cholesterol in the lysosome
      like intracellular compartment. The involvement of annexins and
      cholesterol/sphingomyelin-enriched membrane microdomains in other pathologies
      including cardiac dysfunctions, neurodegenerative diseases, obesity, diabetes
      mellitus, and cancer is likely, but is not supported by substantial experimental
      observations, and therefore awaits further clarification.

PMID- 22159586
TI  - MAPK pathway activation in pilocytic astrocytoma.
AB  - Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central
      nervous system (CNS). A body of research over recent years has demonstrated a key
      role for mitogen-activated protein kinase (MAPK) pathway signaling in the
      development and behavior of PAs. Several mechanisms lead to activation of this
      pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF
      kinase activation subsequent to gene fusion being the most frequent. The high
      specificity of this fusion to PA when compared with other CNS tumors has
      diagnostic utility. In addition, the frequency of alteration of this key pathway
      provides an opportunity for molecularly targeted therapy in this tumor. Here, we
      review the current knowledge on mechanisms of MAPK activation in PA and some of
      the downstream consequences of this activation, which are now starting to be
      elucidated both in vitro and in vivo, as well as clinical considerations and
      possible future directions.

PMID- 22159587
TI  - Principles of mRNA transport in yeast.
AB  - mRNA localization and localized translation is a common mechanism by which
      cellular asymmetry is achieved. In higher eukaryotes the mRNA transport machinery
      is required for such diverse processes as stem cell division and neuronal
      plasticity. Because mRNA localization in metazoans is highly complex, studies at
      the molecular level have proven to be cumbersome. However, active mRNA transport
      has also been reported in fungi including Saccharomyces cerevisiae, Ustilago
      maydis and Candida albicans, in which these events are less difficult to study.
      Amongst them, budding yeast S. cerevisiae has yielded mechanistic insights that
      exceed our understanding of other mRNA localization events to date. In contrast
      to most reviews, we refrain here from summarizing mRNA localization events from
      different organisms. Instead we give an in-depth account of ASH1 mRNA
      localization in budding yeast. This approach is particularly suited to providing
      a more holistic view of the interconnection between the individual steps of mRNA
      localization, from transcriptional events to cytoplasmic mRNA transport and
      localized translation. Because of our advanced mechanistic understanding of mRNA
      localization in yeast, the present review may also be informative for scientists
      working, for example, on mRNA localization in embryogenesis or in neurons.

PMID- 22159588
TI  - Reaching while standing in microgravity: a new postural solution to oversimplify
      movement control.
AB  - Many studies showed that both arm movements and postural control are
      characterized by strong invariants. Besides, when a movement requires
      simultaneous control of the hand trajectory and balance maintenance, these two
      movement components are highly coordinated. It is well known that the focal and
      postural invariants are individually tightly linked to gravity, much less is
      known about the role of gravity in their coordination. It is not clear whether
      the effect of gravity on different movement components is such as to keep a
      strong movement-posture coordination even in different gravitational conditions
      or whether gravitational information is necessary for maintaining motor
      synergism. We thus set out to analyze the movements of eleven standing subjects
      reaching for a target in front of them beyond arm's length in normal conditions
      and in microgravity. The results showed that subjects quickly adapted to
      microgravity and were able to successfully accomplish the task. In contrast to
      the hand trajectory, the postural strategy was strongly affected by microgravity,
      so to become incompatible with normo-gravity balance constraints. The distinct
      effects of gravity on the focal and postural components determined a significant
      decrease in their reciprocal coordination. This finding suggests that movement
      posture coupling is affected by gravity, and thus, it does not represent a unique
      hardwired and invariant mode of control. Additional kinematic and dynamic
      analyses suggest that the new motor strategy corresponds to a global
      oversimplification of movement control, fulfilling the mechanical and sensory
      constraints of the microgravity environment.

PMID- 22159589
TI  - Incidence-based cost estimates require population-based incidence data. A
      critique of Mahan et al.

PMID- 22159590
TI  - Vesicovaginal fistula: what is the preferred closure technique?

PMID- 22159592
TI  - Synthesis of 1,3,4-oxadiazoles from 1,2-diacylhydrazines using [Et2NSF2]BF4 as a
      practical cyclodehydration agent.
AB  - The preparation of 1,3,4-oxadiazoles from 1,2-diacylhydrazines using XtalFluor-E
      ([Et(2)NSF(2)]BF(4)) as cyclodehydration reagent is described. Various
      functionalized 1,3,4-oxadiazoles were synthesized and it was found that the use
      of acetic acid as an additive generally improved the yields.

PMID- 22159591
TI  - Is antibiotic prophylaxis necessary for midurethral sling procedures? A series of
      174 cases without preoperative antibiotics.
AB  - INTRODUCTION AND HYPOTHESIS: Despite the lack of evidence, antibiotic prophylaxis
      has been recommended for midurethral sling procedures. The goal of this study was
      to evaluate the rate of infectious complications in women undergoing midurethral
      sling procedures without antibiotic prophylaxis. METHODS: We reviewed the
      baseline characteristics and postoperative infectious complications of 174
      consecutive women who underwent midurethral sling procedures without prophylactic
      antibiotics from April 2005 to January 2010. Patients undergoing concomitant
      vaginal surgery were excluded. RESULTS: The average age, parity, and body mass
      index of were 51.3 +/- 12.6 years, 2.4 +/- 1.3, and 30.1 +/- 7.4 kg/m(2),
      respectively. There were no wound infections, 2 (1.4%) vaginal mesh exposures and
      12 (8%) cases of bacteriuria. CONCLUSIONS: The risk of infections is low when a
      midurethral sling is performed without antibiotic prophylaxis. Antibiotic
      prophylaxis does not appear to offer any benefit in midurethral sling procedures.

PMID- 22159593
TI  - Torpor use during gestation and lactation in a primate.
AB  - Torpor is an energy-saving mechanism that allows endotherms to overcome energetic
      challenges. Torpor should be avoided during reproduction because of potential
      incompatibility with offspring growth. To test if torpor can be used during
      gestation and lactation to compensate for food shortage, we exposed reproductive
      female grey mouse lemurs (Microcebus murinus), a heterothermic primate, to
      different levels of food availability. Torpor use was characterised by daily skin
      temperature profiles, and its energetic outcome was assessed from changes in body
      mass. Food shortage triggered torpor during the end of the gestation period (n =
      1), ranging from shallow in response to 40% food restriction to deep daily torpor
      in response to 80% restriction. During the early period of lactation, females fed
      ad libitum (n = 2) or exposed to a 40% restriction (n = 4) remained normothermic;
      but 80% food restricted females (n = 5) gave priority to energy saving,
      increasing the frequency and depth of torpor bouts. The use of torpor was
      insufficient to compensate for 80% energetic shortage during lactation resulting
      in loss of mass from the mother and delayed growth in the pups. This study
      provides the first evidence that a heterothermic primate can use torpor to
      compensate for food shortages even during reproduction. This physiological
      flexibility likely evolved as a response to climate-driven fluctuations in food
      availability in Madagascar.

PMID- 22159595
TI  - Adult diffuse gliomas produce mRNA transcripts encoding EGFR isoforms lacking a
      tyrosine kinase domain.
AB  - The epidermal growth factor receptor (EGFR) gene encodes four alternatively
      spliced mRNA, variants 1, 2, 3 and 4, respectively, encoding the whole isoform a
      (EGFR) and truncated isoforms b, c and d, all of which lack the receptor's
      intracellular domain. In addition, a mutant EGFRvIII differs from isoform a in a
      truncated extracellular domain. The expression pattern of these isoforms is
      unknown in adult diffuse gliomas. Thus, we investigated in 47 cases: i) EGFR
      protein expression by immunohistochemistry using an extracellular domain
      recognizing antibody (Ext-Ab) and an intracellular domain specific one (Int-Ab),
      ii) mRNA expression of EGFRv1, -v2, -v3, -v4 and -vIII by RT-PCR and iii) EGFR
      amplification by fluorescent in situ hybridization. The relation of these data
      with histological criteria and patient outcome was studied. The immunostaining
      was stronger with the Ext-Ab than with the Int-Ab. EGFRv1, -v2, -v3 and -v4 mRNA
      expression were highly correlated. They were expressed in all tumors, with
      highest levels in glioblastomas. EGFRv1 strong levels and the presence of vIII
      mRNAs were more closely associated with Int-Ab staining. EGFR gene amplification
      concerned only glioblastomas and was associated with the presence of EGFRvIII and
      high levels of EGFRv2, -v3 and -v4 transcripts. A pejorative outcome was
      associated with: histology (glioblastomas), EGFR amplification, strong Int-Ab
      labeling and high levels of variant mRNAs. Our results indicated that the full
      length EGFR and mutant EGFRvIII are not the sole EGFR isoform expressed in
      diffuse gliomas. This could explain discordant immunohistochemical results
      reported in the literature and may have therapeutic implications.

PMID- 22159596
TI  - Association of aberrant DNA methylation with clinicopathological features in
      breast cancer.
AB  - Aberrant DNA methylation is responsible for the epigenetic silencing of genes
      associated with tumourigenesis and progression of cancer. In this study, we
      assessed the methylation status of eight genes in 49 snap-frozen primary breast
      tumours. Epigenetic alterations of 8 genes were analysed with methylation
      specific polymerase chain reaction (MS-PCR) (DCR1, DAPK1, RASSF1A and DCR2) or
      methylation-sensitive high-resolution melting analysis (MS-HRM) (APC, MGMT, GSTP1
      and PTEN). MS-HRM performance was validated by bisulfite pyrosequencing regarding
      the methylation levels of MGMT. Promoter methylation was observed in APC 54.34%,
      40.4% DCR1, 37.5% DAPK1, 33.3% RASSF1A, 22.44% MGMT, 16.6% GSTP1, 6% PTEN and 0%
      DCR2 promoters, respectively. Interestingly, 37 out of 49 cases (75.5%) displayed
      aberrant promoter methylation in at least one gene. An association of MGMT
      promoter methylation with age and tumour grade was recorded. Moreover, a
      correlation with advanced T-category was elicited for GSTP1, RASSF1 and DAPK1
      promoter methylation. Finally, concurrent methylation of several genes showed a
      marginal statistical relationship with N-category. We conclude that APC, DCR1,
      DAPK1 and RASSF1A promoter methylation represents a common event in breast cancer
      tumourigenesis. Our results suggest that GSTP1, RASSF1, DAPK1 and MGMT may be
      implicated in the acquisition of a more aggressive phenotype in breast cancer.

PMID- 22159597
TI  - Bioinformatics analysis of proteomic profiles during the process of anti-Thy1
      nephritis.
AB  - Anti-Thy1 nephritis is a well-established experimental mesangial proliferative
      nephritis model. Exploring the molecular mechanisms of pathophysiology in anti
      Thy1 nephritis may elucidate the pathogeneses of mesangial proliferation. We
      examined the roles and acting mechanisms of differentially expressed proteins
      (DEPs) by bioinformatics analysis of glomeruli proteomic profiles during the
      course of anti-Thy1 nephritis. In total, 108 DEPs were found by two-dimensional
      fluorescence difference gel electrophoresis (2D-DIGE), and 40 DEPs were
      identified by matrix-assisted laser desorption ionization/time of flight and
      liquid chromatography-MS. DEPs were classified into five clusters (Clusters 1-5),
      according to their expression trends using Cluster 3.0 software, involved in
      regulating biological processes such as the stress response, cell proliferation,
      apoptosis, energy metabolism, transport, and the actin cytoskeleton. The
      expression patterns of ten DEPs, distributed across five clusters, including
      AKR1A1, AGAT, ATP6V1B2, HIBADH, MDH1, MPST, NIT2, PRDX6, PSMB7, and TPI1, were
      validated by Western blotting. Based on Western blotting and
      immunohistochemistry, we also found that the DEP FHL2, which was primarily
      expressed in the mesangial region, was down-regulated on days 3 and 5, and up
      regulated on day 10. In vitro, we found that FHL2 overexpression induced
      mesangial cell proliferation by increasing the number of S-phase cells and
      decreasing G2/M-phase cells, whereas inhibiting FHL2 had the opposite effect.
      This study explored novel DEPs and their expression patterns during anti-Thy1
      nephritis, and elucidated FHL2's effect on mesangial cell proliferation. These
      results will contribute to our understanding of the pathogenesis of mesangial
      proliferation.

PMID- 22159598
TI  - Proteomic identification of betaig-h3 as a lysophosphatidic acid-induced secreted
      protein of human mesenchymal stem cells: paracrine activation of A549 lung
      adenocarcinoma cells by betaig-h3.
AB  - Lysophosphatidic acid (LPA) is enriched in the serum and malignant effusion of
      cancer patients and plays a key role in tumorigenesis and metastasis. LPA
      activated mesenchymal stem cells promote tumorigenic potentials of cancer cells
      through a paracrine mechanism. LPA-conditioned medium (LPA CM) from human adipose
      tissue-derived mesenchymal stem cells (hASCs) elicited adhesion and proliferation
      of A549 human lung adenocarcinoma cells. To identify proteins involved in the LPA
      stimulated paracrine functions of hASCs, we analyzed the LPA CM using liquid
      chromatography tandem mass spectrometry-based shotgun proteomics. We identified
      betaig-h3, an extracellular matrix protein that is implicated in tumorigenesis
      and metastasis, as an LPA-induced secreted protein in hASCs. LPA-induced betaig
      h3 expression was abrogated by pretreating hASCs with the LPA receptor(1/3)
      inhibitor Ki16425 or small interfering RNA-mediated silencing of endogenous
      LPA(1). LPA-induced betaig-h3 expression was blocked by treating the cells with
      the Rho kinase inhibitor Y27632, implying that LPA-induced betaig-h3 expression
      is mediated by the LPA(1)- Rho kinase pathway. Immunodepletion or siRNA-mediated
      silencing of betaig-h3 abrogated LPA CM-stimulated adhesion and proliferation of
      A549 cells, whereas retroviral overexpression of betaig-h3 in hASCs potentiated
      it. Furthermore, recombinant betaig-h3 protein stimulated the proliferation and
      adhesion of A549 human lung adenocarcinoma cells. These results suggest that hASC
      derived betaig-h3 plays a key role in tumorigenesis by stimulating the adhesion
      and proliferation of cancer cells and it can be applicable as a biomarker and
      therapeutic target for lung cancer.

PMID- 22159599
TI  - Regulatory control or oxidative damage? Proteomic approaches to interrogate the
      role of cysteine oxidation status in biological processes.
AB  - Oxidation is a double-edged sword for cellular processes and its role in normal
      physiology, cancer and aging remains only partially understood. Although
      oxidative stress may disrupt biological function, oxidation-reduction (redox)
      reactions in a cell are often tightly regulated and play essential physiological
      roles. Cysteines lie at the interface between these extremes since the chemical
      properties that make specific thiols exquisitely redox-sensitive also predispose
      them to oxidative damage by reactive oxygen or nitrogen species during stress.
      Thus, these modifications can be either under reversible redox regulatory control
      or, alternatively, a result of reversible or irreversible oxidative damage. In
      either case, it has become increasingly important to assess the redox status of
      protein thiols since these modifications often impact such processes as catalytic
      activity, conformational alterations, or metal binding. To better understand the
      redox changes that accompany protein cysteine residues in complex biological
      systems, new experimental approaches have been developed to identify and
      characterize specific thiol modifications and/or changes in their overall redox
      status. In this review, we describe the recent technologies in redox proteomics
      that have pushed the boundaries for detecting and quantifying redox cysteine
      modifications in a cellular context. While there is no one-size-fits-all
      analytical solution, we highlight the rationale, strengths, and limitations of
      each technology in order to effectively apply them to specific biological
      questions. Several technological limitations still remain unsolved, however these
      approaches and future developments play an important role toward understanding
      the interplay between oxidative stress and redox signaling in health and disease.

PMID- 22159601
TI  - Photoinduced reversible changes in morphology of plasmonic Ag nanorods on TiO2
      and application to versatile photochromism.
AB  - We achieved reversible changes in length and spectrum of Ag nanorods based on
      plasmon-induced photoelectrochemical reactions. The changes are applied to multi
      wavelength and dual-polarization photochromism in visible-infrared regions. It
      allows display of invisible images viewable only by infrared cameras. Also
      possible is display of superimposed visible and invisible images.

PMID- 22159600
TI  - Profilin 1 is a potential biomarker for bladder cancer aggressiveness.
AB  - Of the most important clinical needs for bladder cancer (BC) management is the
      identification of biomarkers for disease aggressiveness. Urine is a "gold mine"
      for biomarker discovery, nevertheless, with multiple proteins being in low
      amounts, urine proteomics becomes challenging. In the present study we applied a
      fractionation strategy of urinary proteins based on the use of immobilized metal
      affinity chromatography for the discovery of biomarkers for aggressive BC. Urine
      samples from patients with non invasive (two pools) and invasive (two pools) BC
      were subjected to immobilized metal affinity chromatography fractionation and
      eluted proteins analyzed by 1D-SDS-PAGE, band excision and liquid chromatography
      tandem MS. Among the identified proteins, multiple corresponded to proteins with
      affinity for metals and/or reported to be phosphorylated and included proteins
      with demonstrated association with BC such as MMP9, fibrinogen forms, and
      clusterin. In agreement to the immobilized metal affinity chromatography results,
      aminopeptidase N, profilin 1, and myeloblastin were further found to be
      differentially expressed in urine from patients with invasive compared with non
      invasive BC and benign controls, by Western blot or Elisa analysis, nevertheless
      exhibiting high interindividual variability. By tissue microarray analysis,
      profilin 1 was found to have a marked decrease of expression in the epithelial
      cells of the invasive (T2+) versus high risk non invasive (T1G3) tumors with
      occasional expression in stroma; importantly, this pattern strongly correlated
      with poor prognosis and increased mortality. The functional relevance of profilin
      1 was investigated in the T24 BC cells where blockage of the protein by the use
      of antibodies resulted in decreased cell motility with concomitant decrease in
      actin polymerization. Collectively, our study involves the application of a
      fractionation method of urinary proteins and as one main result of this analysis
      reveals the association of profilin 1 with BC paving the way for its further
      investigation in BC stratification.

PMID- 22159602
TI  - Interactions between CD44 protein and hyaluronan: insights from the computational
      study.
AB  - CD44 is a protein, being a major cell surface receptor for hyaluronan (HA).
      Molecular modeling investigation was carried out on the murine CD44 in complex
      with a HA heptasaccharide in order to: (i) elucidate the nature and dynamics of
      interactions between the HA chain and CD44; (ii) find out if the existence of two
      conformational forms of CD44 discovered in the XRD (X-Ray Diffraction) study can
      be responsible for its switching between low and high affinity for HA. The
      results indicate that the contact of CD44 with HA is dominated by hydrogen
      bonding with small contribution of hydrophobic interactions and salt bridges. In
      addition, the two ('A' and 'B') conformational forms of the HA-CD44 complex
      reported experimentally by Banerji et al. cannot be observed during simulations
      when considering the distance between HA and the sidechain of the R45 residue.
      There exists, however, a free energy barrier associated with the change of the
      phi dihedral angle value at Y46. Additionally, some thermodynamic parameters
      (e.g. the Gibbs free energy change) accompanying the HA binding by CD44 were
      estimated.

PMID- 22159603
TI  - Characterization of a novel ginsenoside-hydrolyzing alpha-L-arabinofuranosidase,
      AbfA, from Rhodanobacter ginsenosidimutans Gsoil 3054T.
AB  - The gene encoding an alpha-L-arabinofuranosidase that could biotransform
      ginsenoside Rc {3-O-[beta-D-glucopyranosyl-(1-2)-beta-D-glucopyranosyl]-20-O
      [alpha-L-arabinofuranosyl-(1-6)-beta-D-glucopyranosyl]-20(S)-protopanaxadiol} to
      ginsenoside Rd {3-O-[beta-D-glucopyranosyl-(1-2)-beta-D-glucopyranosyl]-20-O-beta
      D-glucopyranosyl-20(S)-protopanaxadiol} was cloned from a soil bacterium,
      Rhodanobacter ginsenosidimutans strain Gsoil 3054(T), and the recombinant enzyme
      was characterized. The enzyme (AbfA) hydrolyzed the arabinofuranosyl moiety from
      ginsenoside Rc and was classified as a family 51 glycoside hydrolase based on
      amino acid sequence analysis. Recombinant AbfA expressed in Escherichia coli
      hydrolyzed non-reducing arabinofuranoside moieties with apparent K (m) values of
      0.53 +/- 0.07 and 0.30 +/- 0.07 mM and V (max) values of 27.1 +/- 1.7 and 49.6 +/
      4.1 MUmol min(-1) mg(-1) of protein for p-nitrophenyl-alpha-L-arabinofuranoside
      and ginsenoside Rc, respectively. The enzyme exhibited preferential substrate
      specificity of the exo-type mode of action towards polyarabinosides or
      oligoarabinosides. AbfA demonstrated substrate-specific activity for the
      bioconversion of ginsenosides, as it hydrolyzed only arabinofuranoside moieties
      from ginsenoside Rc and its derivatives, and not other sugar groups. These
      results are the first report of a glycoside hydrolase family 51 alpha-L
      arabinofuranosidase that can transform ginsenoside Rc to Rd.

PMID- 22159604
TI  - Effects of polysaccharides from Morchella conica on nitric oxide production in
      lipopolysaccharide-treated macrophages.
AB  - Morchella conica is a species of rare edible mushroom whose multiple medicinal
      functions have been proven. However, reports barely mention the mechanisms of
      these functions. In this study, the effects of two polysaccharides from M. conica
      (PMCs) on nitric oxide (NO) production in lipopolysaccharide (LPS)-treated
      macrophages were investigated. The results showed that 50-200 MUg/ml of the
      extracellular polysaccharide (EPMC) and 25-200 MUg/ml of the intracellular
      polysaccharide (IPMC) significantly inhibited NO production. Accordingly, the
      signal mechanisms were also explored. It was found that 100 MUg/ml of EPMC and 25
      MUg/ml of IPMC could efficiently down-regulate the inducible nitric oxide
      synthase (iNOS) expression and nuclear factor-kappaB (NF-kappaB) DNA-binding
      activity and up-regulate heme oxygenase 1 (HO-1) expression. Moreover, by using a
      HO-1 inhibitor NaPP to treat the cells, the PMC-inhibited NO production and iNOS
      expression, rather than NF-kappaB activation, were released partially, indicating
      that HO-1 probably medicates the inhibition of PMCs on iNOS and NO. Besides, EPMC
      also significantly suppressed the phosphorylation of p38 mitogen-activated
      protein kinase (p38), c-jun N-terminal kinase, mitogen-activated protein kinase
      kinase 4, and expression of NF-kappaB inducing kinase, while IPMC seemed to show
      no regular effect on p38. In conclusion, PMCs inhibited NO production in LPS
      induced macrophages through regulating a series of signal pathways, suggesting
      that PMCs play a potential role on immunomodulation and treating related
      diseases.

PMID- 22159605
TI  - The complete genome sequence of Pantoea ananatis AJ13355, an organism with great
      biotechnological potential.
AB  - Pantoea ananatis AJ13355 is a newly identified member of the Enterobacteriaceae
      family with promising biotechnological applications. This bacterium is able to
      grow at an acidic pH and is resistant to saturating concentrations of L-glutamic
      acid, making this organism a suitable host for the production of L-glutamate. In
      the current study, the complete genomic sequence of P. ananatis AJ13355 was
      determined. The genome was found to consist of a single circular chromosome
      consisting of 4,555,536 bp [DDBJ: AP012032] and a circular plasmid, pEA320, of
      321,744 bp [DDBJ: AP012033]. After automated annotation, 4,071 protein-coding
      sequences were identified in the P. ananatis AJ13355 genome. For 4,025 of these
      genes, functions were assigned based on homologies to known proteins. A high
      level of nucleotide sequence identity (99%) was revealed between the genome of P.
      ananatis AJ13355 and the previously published genome of P. ananatis LMG 20103.
      Short colinear regions, which are identical to DNA sequences in the Escherichia
      coli MG1655 chromosome, were found to be widely dispersed along the P. ananatis
      AJ13355 genome. Conjugal gene transfer from E. coli to P. ananatis, mediated by
      homologous recombination between short identical sequences, was also
      experimentally demonstrated. The determination of the genome sequence has paved
      the way for the directed metabolic engineering of P. ananatis to produce
      biotechnologically relevant compounds.

PMID- 22159606
TI  - Comparative metabolomic analysis of Saccharomyces cerevisiae during the
      degradation of patulin using gas chromatography-mass spectrometry.
AB  - A comparative metabolomic analysis was conducted on Saccharomyces cerevisiae
      cells with and without patulin treatment using gas chromatography-mass
      spectrometry-based approach. A total of 72 metabolites were detected and
      compared, including 16 amino acids, 29 organic acids and alcohols, 19 sugars and
      sugar alcohols, 2 nucleotides, and 6 miscellaneous compounds. Principle component
      analysis showed a clear separation of metabolome between the cells with and
      without patulin treatment, and most of the identified metabolites contributed to
      the separation. A close examination of the identified metabolites showed an
      increased level of most of the free amino acids, an increased level of the
      intermediates in the tricarboxylic acid cycle, a higher amount of glycerol, a
      changed fatty acid composition, and a decreased level of cysteine and glutathione
      in the cells with patulin treatment. This finding indicated a slower protein
      synthesis rate and induced oxidative stress in the cells with patulin treatment,
      and provided new insights into the effect of toxic chemicals on the metabolism of
      organisms.

PMID- 22159607
TI  - Bioconversion of lignin model compounds with oleaginous Rhodococci.
AB  - Although economically efficient biomass conversion depends on the utilization of
      the complete cell wall (biorefinery concept), including polysaccharides and
      lignin, current biofuels research concentrate mostly on cellulose conversion,
      while lignin is viewed as a side-product that is used primarily as a thermal
      resource. Microbiological conversion of lignin is almost exclusive to fungi,
      usually resulting in increased cell mass and lignolytic enzymes. Some bacteria
      can also degrade lignin-related compounds using the beta-ketoadipate pathway; for
      example, Rhodococcus opacus DSM 1069 can degrade coniferyl alcohol and grow on it
      as sole carbon source. Moreover, this strain belongs to the actinomycetes group
      that is also known for oleaginous species with lipid accumulation over 20%.
      Present work shows that R. opacus DSM 1069 and PD630 strains under nitrogen
      limiting conditions can convert lignin model compounds into triacylglycerols,
      also known as neutral lipids. 4-Hydroxybenzoic and vanillic acid lignin model
      compounds were used as sole carbon sources, and after brief adaptation periods,
      the cells not only began growing but accumulated lipids to the level of
      oleaginicity. These lipids were extracted for transesterification and analysis of
      fatty acid methyl esters showed good composition for biodiesel applications with
      no aromatics. Furthermore, the two strains showed distinct substrate metabolism
      and product profiles.

PMID- 22159608
TI  - Novel magnetic microspheres of P (GMA-b-HEMA): preparation, lipase immobilization
      and enzymatic activity in two phases.
AB  - Magnetic oleic-acid-coated Fe3O4 nanoparticles were first introduced into 1, 1
      diphenylethylene (DPE)-controlled radical polymerization system to prepare
      superparamagnetic microspheres for enzyme immobilization by two steps of
      polymerization. In the presence of DPE, glycidyl methacrylate, 2-hydroxyethyl
      methacrylate and methacryloxyethyl trimethyl ammonium chloride with charge were
      selected as copolymering monomers based on their reactive functional group and
      excellent biocompatibility which were suitable for immobilization of Candida
      rugosa lipase (CRL). The resulting magnetic microspheres were characterized by
      means of scanning electron microscope, Fourier transform infrared spectrum,
      thermogravimetric analysis and vibrating sample magnetometry. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis SDS-PAGE analysis was also conducted
      to demonstrate whether CRL is covalently immobilized or only physically adsorbed.
      The results indicated that the polymerization was successfully carried out, and
      lipase was immobilized on the magnetic microspheres through ionic adsorption and
      covalent binding under mild conditions. The immobilized lipase exhibited high
      activity recovery (69.7%), better resistance to pH and temperature inactivation
      in aqueous phase, as well as superior reusability in nonaqueous phase. The data
      showed that the resulting carrier could hold an amphiphilic property.

PMID- 22159609
TI  - Identification of suitable ionic liquids for application in the enzymatic
      hydrolysis of rutin by an automated screening.
AB  - An automated method in milliliter scale was developed for the screening of
      process parameters concerning the hydrolysis of the flavonoid rutin catalyzed by
      the rhamnosidase activity of naringinase from Penicillium decumbens. Besides the
      effect of additives such as ionic liquids and low molecular salts, the
      productivity in a multiple phase system as well as the recyclability of the
      enzyme in repetitive batches were studied. The hydrophobic ionic liquid (IL)
      trihexyl(tetradecyl)phosphonium bis(trifluormethylsulfonyl)imide
      [P(h(3))t][Tf(2)N] was identified to combine the most favorable characteristics
      out of 23 investigated ILs with regard to enzyme compatibility, substrate
      solubility and enzyme partition coefficient. Also, for the corresponding cations
      1-ethyl-3-methylimidazolium [EMIM], 1-butyl-3-methylimidazolium [BMIM], 1-butyl-1
      methylpyrrolidinium [BMPL] and 1-octyl-3-methylimidazolium [OMIM], the entity
      with the [Tf(2)N] anion was best tolerated by the naringinase. With increasing IL
      content, higher space time yields with up to 1.5 g/(L h) for 80% (v/v)
      [P(h(3))t][Tf(2)N] were achieved. Enhanced specific enzyme activity was observed
      in the presence of Ca(2+) ions. By addition of [P(h(3))t][Tf(2)N] and calcium
      chloride, the reactive aqueous phase was successfully used in three repetitive
      batches with full conversion.

PMID- 22159610
TI  - A novel single-chain Fv antibody for connective tissue growth factor against the
      differentiation of fibroblast into myofibroblast.
AB  - This study was aimed to investigate the effect of a single-chain fragment
      variable antibody of connective tissue growth factor (anti-CTGF scFv) against the
      differentiation of fibroblast into myofibroblast. The scFv antibody was firstly
      expressed in Escherichia coli cells and was then purified by affinity
      chromatography. The yield scFv protein reached a purity over 95% after
      purification. Immunoreactivity assay demonstrated that scFv possessed a special
      affinity toward CTGF. RT-PCR, western blot, and immunofluorescence experiments
      showed that increased expression of alpha-smooth muscle actin induced by TGF
      beta1 could be suppressed by this scFv antibody through inhibiting the
      phosphorylation of Akt.

PMID- 22159611
TI  - A combined physiological and proteomic approach to reveal lactic-acid-induced
      alterations in Lactobacillus casei Zhang and its mutant with enhanced lactic acid
      tolerance.
AB  - Lactobacillus casei has traditionally been recognized as a probiotic and
      frequently used as an adjunct culture in fermented dairy products, where acid
      stress is an environmental condition commonly encountered. In the present study,
      we carried out a comparative physiological and proteomic study to investigate
      lactic-acid-induced alterations in Lactobacillus casei Zhang (WT) and its acid
      resistant mutant. Analysis of the physiological data showed that the mutant
      exhibited 33.8% higher glucose phosphoenolpyruvate:sugar phosphotransferase
      system activity and lower glycolytic pH compared with the WT under acidic
      conditions. In addition, significant differences were detected in both cells
      during acid stress between intracellular physiological state, including
      intracellular pH, H(+)-ATPase activity, and intracellular ATP pool. Comparison of
      the proteomic data based on 2D-DIGE and i-TRAQ indicated that acid stress invoked
      a global change in both strains. The mutant protected the cells against acid
      damage by regulating the expression of key proteins involved in cellular
      metabolism, DNA replication, RNA synthesis, translation, and some chaperones.
      Proteome results were validated by Lactobacillus casei displaying higher
      intracellular aspartate and arginine levels, and the survival at pH 3.3 was
      improved 1.36- and 2.10-fold by the addition of 50-mM aspartate and arginine,
      respectively. To our knowledge, this is the first demonstration that aspartate
      may be involved in acid tolerance in Lactobacillus casei. Results presented here
      may help us understand acid resistance mechanisms and help formulate new
      strategies to enhance the industrial applications of this species.

PMID- 22159612
TI  - Continuous bio-catalytic conversion of sugar mixture to acetone-butanol-ethanol
      by immobilized Clostridium acetobutylicum DSM 792.
AB  - Continuous production of acetone, n-butanol, and ethanol (ABE) was carried out
      using immobilized cells of Clostridium acetobutylicum DSM 792 using glucose and
      sugar mixture as a substrate. Among various lignocellulosic materials screened as
      a support matrix, coconut fibers and wood pulp fibers were found to be promising
      in batch experiments. With a motive of promoting wood-based bio-refinery concept,
      wood pulp was used as a cell holding material. Glucose and sugar mixture
      (glucose, mannose, galactose, arabinose, and xylose) comparable to lignocellulose
      hydrolysate was used as a substrate for continuous production of ABE. We report
      the best solvent productivity among wild-type strains using column reactor. The
      maximum total solvent concentration of 14.32 g L(-1) was obtained at a dilution
      rate of 0.22 h(-1) with glucose as a substrate compared to 12.64 g L(-1) at 0.5
      h(-1) dilution rate with sugar mixture. The maximum solvent productivity (13.66 g
      L(-1) h(-1)) was obtained at a dilution rate of 1.9 h(-1) with glucose as a
      substrate whereas solvent productivity (12.14 g L(-1) h(-1)) was obtained at a
      dilution rate of 1.5 h(-1) with sugar mixture. The immobilized column reactor
      with wood pulp can become an efficient technology to be integrated with existing
      pulp mills to convert them into wood-based bio-refineries.

PMID- 22159613
TI  - Adaptation mechanisms of bacteria during the degradation of polychlorinated
      biphenyls in the presence of natural and synthetic terpenes as potential
      degradation inducers.
AB  - In this study, we examined the effect of polychlorinated biphenyls (PCBs) in the
      presence of natural and synthetic terpenes and biphenyl on biomass production,
      lipid accumulation, and membrane adaptation mechanisms of two PCB-degrading
      bacterial strains Pseudomonas stutzeri and Burkholderia xenovorans LB400.
      According to the results obtained, it could be concluded that natural terpenes,
      mainly those contained in ivy leaves and pine needles, decreased adaptation
      responses induced by PCBs in these strains. The adaptation processes under
      investigation included growth inhibition, lipid accumulation, composition of
      fatty acids, cis/trans isomerization, and membrane saturation. Growth inhibition
      effect decreased upon addition of these natural compounds to the medium. The
      amount of unsaturated fatty acids that can lead to elevated membrane fluidity
      increased in both strains after the addition of the two natural terpene sources.
      The cells adaptation changes were more prominent in the presence of carvone,
      limonene, and biphenyl than in the presence of natural terpenes, as indicated by
      growth inhibition, lipid accumulation, and cis/trans isomerization. Addition of
      biphenyl and carvone simultaneously with PCBs increased the trans/cis ratio of
      fatty acids in membrane fractions probably as a result of fluidizing effects of
      PCBs. This stimulation is more pronounced in the presence of PCBs as a sole
      carbon source. This suggests that PCBs alone have a stronger effect on bacterial
      membrane adaptation mechanisms than when added together with biphenyl or natural
      or synthetic terpenes.

PMID- 22159614
TI  - Biotin protein ligase from Corynebacterium glutamicum: role for growth and L: 
      lysine production.
AB  - Corynebacterium glutamicum is a biotin auxotrophic Gram-positive bacterium that
      is used for large-scale production of amino acids, especially of L-glutamate and
      L-lysine. It is known that biotin limitation triggers L-glutamate production and
      that L-lysine production can be increased by enhancing the activity of pyruvate
      carboxylase, one of two biotin-dependent proteins of C. glutamicum. The gene
      cg0814 (accession number YP_225000) has been annotated to code for putative
      biotin protein ligase BirA, but the protein has not yet been characterized. A
      discontinuous enzyme assay of biotin protein ligase activity was established
      using a 105aa peptide corresponding to the carboxyterminus of the biotin
      carboxylase/biotin carboxyl carrier protein subunit AccBC of the acetyl CoA
      carboxylase from C. glutamicum as acceptor substrate. Biotinylation of this
      biotin acceptor peptide was revealed with crude extracts of a strain
      overexpressing the birA gene and was shown to be ATP dependent. Thus, birA from
      C. glutamicum codes for a functional biotin protein ligase (EC 6.3.4.15). The
      gene birA from C. glutamicum was overexpressed and the transcriptome was compared
      with the control strain revealing no significant gene expression changes of the
      bio-genes. However, biotin protein ligase overproduction increased the level of
      the biotin-containing protein pyruvate carboxylase and entailed a significant
      growth advantage in glucose minimal medium. Moreover, birA overexpression
      resulted in a twofold higher L-lysine yield on glucose as compared with the
      control strain.

PMID- 22159615
TI  - A comparative study of Colles' fractures in patients between fifty and seventy
      years of age: percutaneous K-wiring versus volar locking plating.
AB  - PURPOSE: This retrospective study was to compare the clinical outcomes of volar
      locking plating (VLP) and percutaneous Kirschner wiring (PKW) for the management
      of displaced Colles type distal radius fractures in patients between 50 and 70
      years old. METHODS: There were 31 elderly patients with displaced Colles'
      fractures treated by VLP. We compared them to 31 match-paired patients treated by
      PKW. The patients were matched according to age (within five years) and sex. All
      patients were followed up retrospectively for at least 12 months. The functional
      outcomes and radiological results were compared between the two groups. RESULTS:
      All fractures healed within three months. There were two complications (6.5%) in
      the PKW group and one complication (3.2%) in the VLP group. At final follow-up,
      wrist flexion, extension, and ulnar deviation were significantly better in the
      VLP group compared with the PKW group (all p values<0.05). According to modified
      Green and O'Brien criteria, the VLP group showed a trend towards increased rate
      of satisfactory outcome compared with the PKW group (p = 0.09). CONCLUSION: For
      the treatment of displaced Colles' fractures in patients between 50 and 70 years
      old, both groups had high union rate and low complication rate. However, better
      functional results can be expected in association with open reduction and volar
      locking plating.

PMID- 22159616
TI  - [Gestational diabetes, what did change in the criteria for diagnosis?].

PMID- 22159617
TI  - [Maternal and perinatal outcomes in pregnant women with leukemia].
AB  - PURPOSE: To describe the maternal and perinatal outcomes of pregnant women
      diagnosed with leukemia who were followed up for prenatal care and delivery at a
      university hospital. METHODS: A retrospective study of the period from 2001 to
      2011, which included 16 pregnant women with a diagnosis of leukemia followed by
      antenatal care specialists in hematological diseases and pregnancy. For acute
      leukemia diagnosed after the first trimester, the recommendation was to perform
      chemotherapy despite the current pregnancy. For chronic leukemia, patients who
      were controlled in hematological terms were maintained without medication during
      pregnancy, or chemotherapy was introduced after the first trimester. We analyzed
      the maternal and perinatal outcome. RESULTS: Acute lymphoblastic leukemia (ALL)
      was diagnosed in five cases (31.3%), acute myeloid leukemia (AML) in two cases
      (12.5%) and chronic myeloid leukemia (CML) in nine cases (56.3%). Of the cases of
      acute leukemia, two (28.6%) were diagnosed in the first trimester, two (28.6%) in
      the second and three (42.9%) in the third. Two patients with ALL diagnosed in the
      first trimester opted for therapeutic abortion. Four patients with acute leukemia
      received chemotherapy during pregnancy, with a diagnosis established after the
      20th week. In one case of ALL with a late diagnosis (30 weeks), chemotherapy was
      started after delivery. All pregnant women with acute leukemia developed anemia
      and thrombocytopenia, and four (57.1%) developed febrile neutropenia. Of nine
      pregnant women with CML, four were treated with imatinib mesylate when they
      became pregnant, with treatment being interrupted in the first trimester in three
      of them and in the second trimester in one. During pregnancy, three patients
      (33.3%) required no chemotherapy after discontinuation of imatinib, and six
      (66.7%) were treated with the following drugs: interferon (n=5) and/or
      hydroxyurea (n=3 ). In the group of pregnant women with CML, anemia occurred in
      four (44.4%) cases and thrombocytopenia in one (11.1%). The perinatal outcomes of
      pregnancies complicated by acute leukemia were as follows: mean gestational age
      at delivery was 32 weeks (standard deviation - SD=4.4) and the mean birth weight
      was 1476 g (SD=657 g), there were 2 (40.0%) perinatal deaths (a fetal one and a
      neonatal one). In pregnancies complicated by CML, the mean gestational age at
      delivery was 37.6 weeks (SD=1.1) and the mean birth weight was 2870 g (SD=516 g).
      There was no perinatal death and no fetal abnormality was detected. CONCLUSIONS:
      Maternal and fetal morbidity is high in pregnancies complicated by acute
      leukemia. Whereas, in pregnancies complicated by CML, the maternal and fetal
      prognosis appears to be more favorable, with greater ease in management of
      complications.

PMID- 22159618
TI  - [Assessment of psychosocial adaptation to pregnancy in Brazilian pregnant women].
AB  - PURPOSE: to evaluate psychosocial adaptation to pregnancy by translating and
      cross-culturally adapting a specific assessment instrument to be used with
      Brazilian women. METHODS: this was a cross-sectional observational study. the
      translation and cross-cultural adaptation and of the Prenatal Self-evaluation
      Questionnaire (PSeQ) was performed following all the required methodological
      steps. another questionnaire was applied to characterize the sociodemographic and
      clinical status of the pregnant women (n=36). Statistical analysis consisted of
      the determination of the mean and standard deviation (SD) and of absolute and
      relative frequency. the statistical test used for the analysis of internal
      consistency was Cronbach's alpha coefficient, using SPSS version 17.0. RESULTS:
      the volunteers were of low socioeconomic status, aged on average 25.1 years (
      5.5), and had an average gestational age of 25.9 weeks ( 8.1). 58.3% of these
      volunteers had not planned their current pregnancy. the pretest showed that 75%
      of the pregnant women found the questionnaire easy to understand. Regarding the
      PSeQ instrument, the identification with the maternal role was the subcategory
      which showed the highest average, 24.8 ( 5.6), while the relationship with the
      mother had the lowest average 15.4 ( 7.7). the internal consistency ranged from
      0.52 to 0.89. CONCLUSION: the assessment of psychosocial adaptation to pregnancy
      in pregnant women is very important during the progress of pregnancy and permits
      intervention through obstetric-neonatal actions of promotion and prevention
      regarding the well-being of mother and child.

PMID- 22159619
TI  - [Epidemiological and nutritional characteristics of pregnant HIV-infected women].
AB  - PURPOSE: To describe the epidemiological profile and nutritional status of
      pregnant women infected with human immunodeficiency virus (HIV) and its effect on
      the nutritional status of these women during pregnancy. METHODS: A retrospective
      cohort study was conducted on 121 pregnant women with HIV infection, single fetus
      pregnancies, who received prenatal care and delivered at a referral unit for HIV
      infected pregnant women during the period from 1997 to 2007. Outcomes of the
      study were the initial and final nutritional status as measured by body mass
      index, weight gain, anemia (hemoglobin <11 g/dL) and low birth weight. Bivariate
      analysis investigated the association of these outcomes with socio-demographic,
      clinical-care and dietary characteristics. We estimated the relative risks (RR)
      with 95% confidence intervals (CI). RESULTS: At the beginning of pregnancy, 11.0%
      of the women were underweight, and in late pregnancy, the prevalence was 29.3%.
      Low educational level, urinary infection and worm infestation were associated
      with low gestational weight in late pregnancy. The percentage of insufficient
      weight gain was 47.5%, with well-nourished pregnant women (RR=3.3 95%CI 1.3-8.1)
      and women with no companion (RR=1.5 95%CI 1.1-2.2) having a higher risk for this
      outcome. The prevalences of overweight at the beginning and at the end of
      pregnancy were 26.8 and 29.4, respectively. There was a significant prevalence of
      anemia (61.0%). CONCLUSIONS: The high percentage of negative nutritional outcomes
      identified at this referral service with multidisciplinary care for pregnant
      women living with HIV reveals the need to establish more effective strategies to
      deal with the complex context of HIV.

PMID- 22159620
TI  - [Clinical predictors of asymptomatic bacteriuria during pregnancy].
AB  - PURPOSE: To estimate the prevalence of asymptomatic bacteriuria among pregnant
      women attended at our university prenatal care clinic and to identify probable
      clinical predictors. METHODS: Across-sectional study was carried out from August
      2008 to October 2009 at the Bahiana School of Medicine involving 260 pregnant
      women without symptoms of urinary tract infection. The following exclusion
      criteria were considered: presence of clinical signs such as fever, dysuria,
      vesical tenesmus, lumbar pain, history of active genital bleeding or loss of
      amniotic fluid, use of antimicrobial agents in the 30 days prior to sample
      collection, and refusal to participate in the project. The presence of single
      pathogen bacterial colonization >=10(5) CFU/mL in the urine sample obtained from
      the middle jet was considered to be a dependent variable. The predictive factors
      evaluated were as follows: age, race, marital status, schooling, gestational age,
      hypertension, anemia, vaginal infection, sickle cell trait and previous history
      of urinary tract infection, urinary symptoms related to the lower urinary tract
      (frequency, urgency and nocturia) and data obtained from the urine summary
      (leukocyturia, increased bacterial flora, hematuria, proteinuria, and presence of
      nitrite). Statistical analysis was performed with the Statistical Package for the
      Social Sciences (SPSS) software version 13.0 and the level of significance was
      set at p<0.05. Prevalences were expressed as percentage, and the confidence
      interval considered was 95% (95%CI). RESULTS: The prevalence of asymptomatic
      bacteriuria was 12.3% (95%CI=8.3-16.3). E. coli was the most frequent etiologic
      agent (59.4%). Logistic regression indicated that urgency to void (OR=5.99;
      95%CI=2.20-16.31; p<0.001); leukocyturia (OR=2.85; 95%CI=1.04-7.83; p=0.042) and
      increased bacterial flora (OR=10.62; 95%CI=3.95-28.56; p<0.001) were independent
      predictors of asymptomatic bacteriuria. CONCLUSION: The prevalence of
      asymptomatic bacteriuria in the studied population was high. The prediction score
      created for the final logistic regression model has an accuracy of 91.9% for
      bacteriuria.

PMID- 22159621
TI  - [Impact of the myoma arterial embolization by uterine volume, diameter myoma
      greater and in the ovarian function].
AB  - PURPOSE: To evaluate the impact of uterine artery embolization (UAE) on uterine
      volume (UV), greater myoma diameter (GMD) and ovarian function three months after
      the procedure, by transvaginal pelvic ultrasonography (TVPUS) and by the
      determination of follicle-stimulating hormone (FSH). METHODS: Thirty patients
      with leiomyomas were submitted to UAE. TVPUS and FSH determination were performed
      before and three months after UAE. UV was determined in cm3, GMD in cm and FSH in
      IU/mL. Data are reported as as mean standard deviation (SD) and were analyzed
      statistically by the nonparametric Mann-Whitney test. RESULTS: Twenty-nine
      patients were analyzed. Before UAE, mean UV was 402.4 165.9 cm3 and GMD was 5.9
      2.1 cm. After UAE, mean UV was 258.9 118.6 cm3 and GMD was 4.6 1.8 cm. Mean FSH
      concentration was 4.9 3.5 IU/mL before UAE and 5.5 4.7 IU/mL after UAE, with
      p=0.5. There was a 35% reduction of UV and a 22% reduction of GMD, with no
      changes in FSH values after three months. CONCLUSION: The procedure significantly
      reduced UV and GMD but did not cause a significant increase in FSH levels, thus
      causing no changes in ovarian function.

PMID- 22159622
TI  - [Factors associated with changes in energy intake of women after treatment for
      breast cancer].
AB  - PURPOSE: To investigate changes in the dietary consumption as well as the
      influence of the general characteristics, of the sociodemographic, clinical and
      nutritional factors, and of the antineoplastic therapy on the changes in the
      energy intake of women from southern Brazil, before and after adjuvant therapy
      for breast cancer. METHODS: A non-randomized clinical study was conducted on 53
      patients at a hospital of the public health network. Dietary information was
      collected with a food frequency questionnaire. A mixed-effects linear regression
      model was used to evaluate the factors that influenced longitudinal alterations
      of energy intake. RESULTS: A significant increase was observed in daily energy
      intake of fats, calcium, iron, copper, polyunsaturated fatty acids, omega 6 and
      omega 3, and a significant decrease in vitamin B2 intake. The final regression
      model for the change in energy intake showed an average increase of 19.2
      kcal/month. Fruit and legume consumption showed the highest association with
      energy intake, with each 100 g consumed resulting in an average increase of 68.4
      and 370.5 kcal, respectively. Women in the 51 to 60 year age range consumed 403.5
      kcal less than those in the 31 to 50 year age range. CONCLUSION: There was an
      increase in energy intake during treatment and the increase in the ingestion of
      fruits and legumes was associated with significant increases in energy intake.

PMID- 22159623
TI  - [Hyperandrogenic syndrome in a postmenopausal woman: a case report].
AB  - Hyperandrogenic syndromes include diseases that manifest through an increased
      biological activity of androgens and that can originate from neoplastic or
      functional diseases. Androgen-secreting ovarian tumors represent about 1% of
      ovarian neoplasias. Steroid cell tumors are among the more rare types which
      account for less than 0.1% of all ovarian tumors. They are usually benign, of
      small dimensions and unilateral. We report here a rare case of a unilateral
      steroid cell tumor. A 60-year-old woman was seen after four months of evolution
      of hirsutism, clitoris hypertrophy and elevation of serum estradiol levels. Her
      total testosterone and 17-OH-progesterone levels were also increased.

PMID- 22159624
TI  - Ligand-guided pathway selection in nickel-catalyzed couplings of enals and
      alkynes.
AB  - Nickel-catalyzed couplings of enals and alkynes utilizing triethylborane as the
      reducing agent illustrate a significant dependence on ligand structure. Simple
      variation of monodentate phosphines allows selective access to alkylative
      couplings or reductive cycloadditions, while further variation of reaction
      conditions provides clean access to reductive couplings and redox-neutral
      couplings.

PMID- 22159625
TI  - Evidence-based policy revisited: orientation towards the policy process and a
      public health policy science.

PMID- 22159626
TI  - Triplatin, a platelet aggregation inhibitor from the salivary gland of the
      triatomine vector of Chagas disease, binds to TXA(2) but does not interact with
      glycoprotein PVI.
AB  - Salivary glands from haematophagous animals express a notable diversity of
      negative modulators of platelet function. Triplatin is an inhibitor of collagen
      induced platelet aggregation which has been described as an antagonist of
      glycoprotein VI (GPVI). Because triplatin displays sequence homology to members
      of the lipocalin family of proteins, we investigated whether triplatin mechanism
      of action could be explained by interaction with pro-haemostatic prostaglandins.
      Our results demonstrate that triplatin inhibits platelet aggregation induced by
      low doses of collagen, thromboxane A2 (TXA(2)) mimetic (U46619), and arachidonic
      acid (AA). On the other hand, it does not inhibit platelet aggregation by
      convulxin, PMA, or low-dose ADP. Isothermal titration calorimetry (ITC) revealed
      that triplatin binds AA, cTXA(2), TXB(2), U46619 or prostaglandin (PG)H(2)
      mimetic (U51605). Consistent with its ligand specificity, triplatin induces
      relaxation of rat aorta contracted with U46619. Triplatin also interacts with
      PGF(2alpha) and PGJ(2), but not with leukotrienes, AA or biogenic amines. Surface
      plasmon resonance experiments failed to demonstrate interaction of triplatin with
      GPVI; it also did to inhibit platelet adhesion to fibrillar or soluble collagen.
      Because triplatin displays sequence similarity to apolipoprotein D (ApoD) - a
      lipocalin associated with high-density lipoprotein, ApoD was tested as a putative
      TXA(2)-binding molecule. ITC failed to demonstrate binding of ApoD to all
      prostanoids described above, or to AA. Furthermore, ApoD was devoid of inhibitory
      properties towards platelets activation by AA, collagen, or U46619. In
      conclusion, triplatin mechanism of action has been elucidated without ambiguity
      as a novel TXA(2)- and PGF(2alpha)- binding protein. It conceivably blocks
      platelet aggregation and vasoconstriction, thus contributing to successful blood
      feeding at the vector-host interface.

PMID- 22159627
TI  - Overexpression of SGLT1 is correlated with tumor development and poor prognosis
      of ovarian carcinoma.
AB  - PURPOSE: Overexpression of glucose transporters has been identified in a variety
      of human cancers. However, the expression status of Sodium dependent Glucose
      Transporter 1 (SGLT1) in ovarian carcinoma has not been investigated. METHODS: In
      our study, protein expression levels of SGLT1 were explored by semiquantitative
      immunohistochemical staining on archival formalin-fixed paraffin-embedded
      pathologic specimen consisting of 178 epithelial ovarian tumors. Receiver
      operating characteristic curve analysis, Spearman's rank correlation, Kaplan
      Meier plots and Cox proportional hazards regression model were utilized to
      analyze the data. RESULTS: The threshold for high expression of SGLT1 was
      determined to be above 40% (areas under curve = 0.683, P = 0.003) based on the
      area under curves. Significantly overexpression of SGLT1 was observed in 39.7%
      invasive carcinomas, 11.5% borderline tumors, 10% cystadenomas but in none of the
      normal ovaries (0%). In ovarian carcinomas, SGLT1 overexpression was positively
      correlated with later pT status (P = 0.029) and advanced FIGO stage (P = 0.024).
      By univariate survival analysis on the ovarian carcinoma cohorts, overexpression
      of SGLT1 was associated with shortened patient survival (mean 70.5 months in
      tumors with overexpression of SGLT1 versus 89.3 months in tumors with normal
      levels of SGLT1; P = 0.019). By multivariate analysis, SGLT1 protein expression
      remained as a significant and independent prognostic factor for the prediction of
      patient survival (P = 0.033). CONCLUSIONS: SGLT1 overexpression, as examined by
      immunohistochemistry, is an independent biomarker for poor prognosis of patients
      with ovarian carcinoma.

PMID- 22159628
TI  - Cutting through the clutter: searching for targets in evolving complex scenes.
AB  - We evaluated the use of visual clutter as a surrogate measure of set size effects
      in visual search by comparing the effects of subjective clutter (determined by
      independent raters) and objective clutter (as quantified by edge count and
      feature congestion) using "evolving" scenes, ones that varied incrementally in
      clutter while maintaining their semantic continuity. Observers searched for a
      target building in rural, suburban, and urban city scenes created using the game
      SimCity. Stimuli were 30 screenshots obtained for each scene type as the city
      evolved over time. Reaction times and search guidance (measured by scan path
      ratio) were fastest/strongest for sparsely cluttered rural scenes, slower/weaker
      for more cluttered suburban scenes, and slowest/weakest for highly cluttered
      urban scenes. Subjective within-city clutter estimates also increased as each
      city matured and correlated highly with RT and search guidance. However, multiple
      regression modeling revealed that adding objective estimates failed to better
      predict search performance over the subjective estimates alone. This suggests
      that within-city clutter may not be explained exclusively by low-level feature
      congestion; conceptual congestion (e.g., the number of different types of
      buildings in a scene), part of the subjective clutter measure, may also be
      important in determining the effects of clutter on search.

PMID- 22159629
TI  - Roles of the upper and lower bodies in direction discrimination of point-light
      walkers.
AB  - We can easily recognize human movements from very limited visual information
      (biological motion perception). The present study investigated how upper and
      lower body areas contribute to direction discrimination of a point-light (PL)
      walker. Observers judged the direction that the PL walker was facing. The walker
      performed either normal walking or hakobi, a walking style used in traditional
      Japanese performing arts, in which the amount of the local motion of extremities
      is much smaller than that in normal walking. Either the upper, lower, or full
      body of the PL walker was presented. Discrimination performance was found to be
      better for the lower body than for the upper body. We also found that
      discrimination performance for the lower body was affected by walking style
      and/or the amount of local motion signals. Additional eye movement analyses
      indicated that the observers initially inspected the region corresponding to the
      upper body, and then the gaze shifted toward the lower body. This held true even
      when the upper body was absent. We conjectured that the upper body subserved to
      localize the PL walker and the lower body to discriminate walking direction. We
      concluded that the upper and lower bodies play different roles in direction
      discrimination of a PL walker.

PMID- 22159630
TI  - Optimal decisions for contrast discrimination.
AB  - Contrast discrimination functions for simple gratings famously look like a
      dipper. Discrimination thresholds are lower than detection thresholds for
      moderate pedestal contrasts, and the rate of growth of thresholds as the pedestal
      contrast gets larger typically lies between the values implied by two popular
      treatments of noise. Here, we suggest a new normative treatment of the dipper,
      showing how it emerges from Bayesian inference based on the responses of a
      population of orientation-tuned units. Our central assumption concerns the noise
      corrupting the outputs of these units as a function of the contrast: We suggest
      that it has the shape of a hinge. We show the match to the psychophysical data
      and discuss the neurobiological and statistical rationales for this form of
      noise. Finally, we relate our model to other major accounts of contrast
      discrimination.

PMID- 22159631
TI  - Redundancy gains in pop-out visual search are determined by top-down task set:
      behavioral and electrophysiological evidence.
AB  - We combined behavioral and electrophysiological measures to find out whether
      redundancy gain effects in pop-out visual search are exclusively determined by
      bottom-up salience or are modulated by top-down task search goals. Search arrays
      contained feature singletons that could be defined in a single dimension (color
      or shape) or redundantly in both dimensions. In the baseline condition, both
      color and shape were task-relevant, and behavioral redundancy gain effects were
      accompanied by an earlier onset of the N2pc component for redundant as compared
      to single-dimension targets. This demonstrates that redundancy gains are
      generated at an early visual-perceptual level of processing. In the color target
      and shape target conditions, only one dimension was task-relevant, while the
      other could be ignored. In these two conditions, behavioral and
      electrophysiological redundancy gains were eliminated. We conclude that redundant
      signals effects in pop-out visual search are not driven by bottom-up salience but
      are instead strongly dependent on top-down task set.

PMID- 22159632
TI  - Differential responsiveness to 17beta-estradiol of mesenchymal stem cells from
      postmenopausal women between osteoporosis and osteoarthritis.
AB  - Differential osteogenic potential and responsiveness to 17beta-estradiol (E2) of
      mesenchymal stem cells (MSCs) were found between postmenopausal women with
      osteoporosis (OP) and osteoarthritis (OA). These results suggest differential
      biological mechanisms of estrogen deficiency in regulation of bone remodeling
      between OP and OA. INTRODUCTION: OP and OA are two common disorders in
      postmenopausal women. The inverse relationship has been suggested between OP and
      OA, but their mechanisms that relate to estrogen deficiency are not fully
      understood. The aim of this study was to compare the differential responsiveness
      to E2 of MSCs from osteoporotic versus osteoarthritic donors. METHODS: Twenty
      postmenopausal patients, ten with osteoporotic hip fractures and ten with hip
      osteoarthritis, were included into this study. MSCs were derived from cancellous
      bones of femoral heads from OA and OP donors and cultured in osteogenic and
      adipogenic medium with or without E2 added. The alkaline phosphatase (ALP)
      activity, calcium content, calcified nodules, lipid droplets, messenger RNA
      (mRNA) expression of ALP, osteocalcin (OC), collagen 1alpha (COL1alpha),
      peroxisome proliferators-activated receptor gamma2 (PPARgamma2) and lipoprotein
      lipase (LPL) were measured and compared between two groups with OP and OA.
      RESULTS: In osteogenic medium, ALP activity, calcium content and mRNA expression
      of OC and COL1alpha in MSCs from OA were significantly higher than those from OP
      group. In adipogenic condition, there was no significant difference in lipid
      droplets formation and mRNA expression of PPARgamma2 and LPL between OP and OA
      groups. With E2 added in osteogenic medium, ALP activity, calcium content and OC
      mRNA were significantly higher in OP group than in OA group, whereas E2 had no
      significant effect on lipid droplet formation and mRNA expression of PPARgamma2
      and LPL. CONCLUSION: Differential osteogenic potential and responsiveness to E2
      of MSCs were found between postmenopausal women with OP and OA. These results may
      provide information for clinical application of MSCs in the differential setting
      of estrogen deficiency.

PMID- 22159633
TI  - A clinical decision rule to enhance targeted bone mineral density testing in
      healthy mid-life women.
AB  - SUMMARY: The rates of bone mineral density testing for osteoporosis among healthy
      mid-life women are high, although their osteoporosis or fracture risk is low. To
      reduce unnecessary testing, we created and evaluated a tool to guide bone density
      testing based on the woman's age, weight, fracture history, and menopausal
      status. INTRODUCTION: This study aims to improve case finding of mid-life women
      with low bone mass on bone mineral density (BMD) assessment. METHODS: Among
      healthy women aged 40-60 years having their first BMD test, osteoporosis risk
      factors were assessed by questionnaire and BMD by dual-energy X-ray
      absorptiometry. The combination of risk factors that best discriminated women
      with/without low bone mass (T-score <= -2.0) was determined from the logistic
      regression model area under the curve (AUC) and internally validated using
      bootstrapping. Using the model odds ratios, a clinical prediction rule was
      created and its discriminative properties assessed and compared with that of the
      osteoporosis self-assessment tool (OST). Sensitivity analyses examined results
      for pre-/peri- and post-menopausal women, separately. RESULTS: Of 1,664 women
      referred for baseline BMD testing, 433 with conditions known to be associated
      with bone loss were excluded. Of 1,231 eligible women, 944 (77%) participated and
      87 (9.2%) had low bone mass (35 pre-/peri- and 52 post-menopausal). Four risk
      factors for low bone mass were identified and incorporated into a clinical
      prediction rule. Selecting women for BMD testing with weight of <=70 kg or any
      two of age >51, years' post-menopause of >=1, and history of fragility fracture
      after age 40 was associated with 93% sensitivity to identify women with low bone
      mass, compared with 47% sensitivity for an OST score of <=1 (AUC 0.75 versus OST
      AUC 0.69, p = 0.04). Results restricted to post-menopausal women were similar.
      CONCLUSIONS: Among healthy mid-life women receiving a baseline BMD test, few had
      low bone mass, supporting the need for guidance about testing. A prediction rule
      with four risk factors had improved sensitivity over the OST. Further validation
      is warranted.

PMID- 22159634
TI  - Glutamine prevents intestinal mucosal injury induced by cyclophosphamide in rats.
AB  - PURPOSE: High doses of anticancer drugs often damage the intestinal mucosa. The
      purpose of the present study was to examine the effect of glutamine on mucosal
      damage induced by cyclophosphamide in a rat model, and to elucidate the
      mechanisms responsible for its protective effects. METHOD: Rats were randomly
      assigned to one of the three experimental groups. Group A (control) (n = 8):
      intraperitoneal injection of saline, group B (n = 8): intraperitoneal injection
      of cyclophosphamide (300 mg/kg), group C (n = 8): intraperitoneal injection of
      cyclophosphamide (300 mg/kg) and oral glutamine (1.0 g/kg). After 3 days, the
      ileal segment was removed for morphological and the biochemical analyses. We also
      evaluated the level of mucosal apoptosis by the TUNEL method and enterocyte
      proliferation using bromodeoxyuridine (BrdU). RESULTS: Mucosal atrophy was
      observed in group B but not in groups A or C. The mucosal wet weight, protein and
      glutathione levels were significantly decreased in group B compared with group A,
      and were increased significantly in group C compared with group B. While
      enterocyte proliferation significantly decreased and the apoptotic index
      significantly increased in group B compared with group A, a significant increase
      in the enterocyte proliferation and a significant decrease in apoptosis were
      observed in group C compared with group B. CONCLUSIONS: Glutamine prevented
      intestinal mucosal injury induced by cyclophosphamide via increased glutathione,
      decreased apoptosis and increased proliferation of intestinal epithelial cells.

PMID- 22159635
TI  - Presence and potential role of thermophilic bacteria in temperate terrestrial
      environments.
AB  - Organic sulfur and nitrogen are major reservoirs of these elements in terrestrial
      systems, although their cycling remains to be fully understood. Both sulfur and
      nitrogen mineralization are directly related to microbial metabolism. Mesophiles
      and thermophiles were isolated from temperate environments. Thermophilic isolates
      were classified within the Firmicutes, belonging to the Geobacillus,
      Brevibacillus, and Ureibacillus genera, and showed optimum growth temperatures
      between 50 degrees C and 60 degrees C. Sulfate and ammonium produced were higher
      during growth of thermophiles both for isolated strains and natural bacterial
      assemblages. They were positively related to organic nutrient load. Temperature
      also affected the release of sulfate and ammonium by thermophiles. Quantitative,
      real-time reverse-transcription polymerase chain reaction on environmental
      samples indicated that the examined thermophilic Firmicutes represented up to
      3.4% of the total bacterial community RNA. Temperature measurements during summer
      days showed values above 40 degrees C for more than 10 h a day in soils from
      southern Spain. These results support a potential role of thermophilic bacteria
      in temperate terrestrial environments by mineralizing organic sulfur and nitrogen
      ruled by the existence and length of warm periods.

PMID- 22159636
TI  - (Z)-9-tricosene identified in rectal gland extracts of Bactrocera oleae males:
      first evidence of a male-produced female attractant in olive fruit fly.
AB  - It is well-known that Bactrocera oleae (olive fruit fly) females attract
      conspecific males by using 1,7-dioxaspiro[5,5]undecane (1) as the main component
      of their sex pheromone, and that 1 is produced in the female rectal gland.
      Although some authors have claimed that B. oleae males also attract females, to
      date no male-produced female attractants have been found in this species. In this
      paper, we report the first identification of a substance unique to males and able
      to attract females. The findings of the study include the following: (1) females
      responded in a bioassay to hexane extracts obtained from rectal glands of 15-day
      old B. oleae males, (2) the presence of (Z)-9-tricosene (2) was consistently and
      unambiguously identified in these extracts using gas chromatography (GC) and GC
      mass spectrometry methods, (3) in preliminary bioactivity tests, low doses
      (equivalent to a few males) of chemically and stereoisomerically pure synthetic
      (Z)-9-tricosene (2) attracted olive fruit fly females. Interestingly, compound 2,
      commonly called muscalure, is also a well-known component of the house fly (Musca
      domestica) sex pheromone.

PMID- 22159637
TI  - Exploring structural change of protein bovine serum albumin by external
      perturbation using extrinsic fluorescence probe: spectroscopic measurement,
      molecular docking and molecular dynamics simulation.
AB  - Structural modification through binding interaction of plasma protein bovine
      serum albumin (BSA) with an extrinsic charge transfer fluorophore 5-(4
      dimethylamino-phenyl)-penta-2,4-dienoic acid (DMAPPDA) and its response to
      external perturbation due to interactions with surfactant sodium dodecyl sulphate
      (SDS) have been explored at physiological pH by steady state absorption,
      emission, fluorescence anisotropy, red edge excitation shift, far-UV circular
      dichroism and time resolved spectral measurements in combination with Molecular
      Docking and Molecular Dynamics (MD) simulation. Interaction of the probe with BSA
      is reflected by a small change in protein secondary structure with fluorescence
      enhancement and blue shift of probe emission. Molecular docking studies revealed
      that the probe binds to the hydrophobic cavity of sub-domain IIA of BSA. The
      distance for energy transfer from the tryptophan of BSA to the bound DMAPPDA
      measured by Fluorescence Resonance Energy Transfer is in good agreement with the
      molecular docking results. MD simulation predicts stabilization of the complex
      with respect to the bare molecule. Interaction of BSA and SDS with DMAPPDA
      supports the movement of the probe from hydrophilic free water region to a more
      restricted hydrophobic zone inside the protein.

PMID- 22159638
TI  - Valproic acid overcomes hypoxia-induced resistance to apoptosis.
AB  - Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), has been shown to
      be an effective tool in cancer treatment. Although its ability to induce
      apoptosis has been described in many cancer types, the data come from experiments
      performed in normoxic (21% O2) conditions only. Therefore, we questioned whether
      VPA would be equally effective under hypoxic conditions (1% O2), which is known
      to induce resistance to apoptosis. Four neuroblastoma cell lines were used: UKF
      NB-3, SK-N-AS, plus one cisplatin-resistant subline derived from each of the two
      original sensitive lines. All were treated with VPA and incubated under hypoxic
      conditions. Measurement of apoptosis and viability using TUNEL assay and Annexin
      V/propidium iodide labeling revealed that VPA was even more effective under
      hypoxic conditions. We show here that hypoxia-induced resistance to
      chemotherapeutic agents such as cisplatin could be overcome using VPA. We also
      demonstrated that apoptosis pathways induced by VPA do not differ between
      normoxic and hypoxic conditions. VPA-induced apoptosis proceeds through the
      mitochondrial pathway, not the extrinsic pathway (under both normoxia and
      hypoxia), since inhibition of caspase-8 failed to decrease apoptosis or influence
      bid cleavage. Our data demonstrated that VPA is more efficient in triggering
      apoptosis under hypoxic conditions and overcomes hypoxia-induced resistance to
      cisplatin. The results provide additional evidence for the use of VPA in
      neuroblastoma (NBL) treatment.

PMID- 22159639
TI  - Reduced motor asymmetry in older adults when manually tracing paths.
AB  - Handedness, a preference towards using the right or left hand, is established in
      early childhood. Such specialisation allows a higher level of skill to be
      maintained in the preferred hand on specific tasks through continuous practice
      and performance. Hand asymmetries might be expected to increase with age because
      of the time spent practising with the preferred hand. However, neurophysiological
      work has suggested reduced hemispheric function lateralisation in the ageing
      brain, and behavioural studies have found reduced motor asymmetries in older
      adults (Przybyla et al., in Neurosci Lett 489:99-104, 2011). We therefore tested
      the predictions of behavioural change from reduced hemispheric function by
      measuring tracing performance (arguably one of the most lateralised of human
      behaviours) along paths of different thickness in a group of healthy young and
      older adults. Participants completed the task once with their preferred (right)
      hand and once with their non-preferred (left) hand. Movement time (MT) and shape
      accuracy (SA) were dependant variables. A composite measure of MT and SA, the
      speed accuracy cost function (SACF) provided an overall measure of motor
      performance. Older participants were slower and less accurate when task demands
      were high. Combined analyses of both hands revealed reduced asymmetries in MT and
      SACF in the older group. The young were significantly faster when tracing with
      their preferred hand, but older participants were equally slow with either hand.
      Our results are consistent with the growing literature reporting decreased
      hemispheric function lateralisation in the ageing brain.

PMID- 22159641
TI  - Tripeptide self-assembled hydrogels: unexpected twists of chirality.
AB  - Change of chirality of the first N-terminal amino acid of tripeptides VFF and FFV
      from l to d results in self-assembled hydrogels at physiological pH from non
      assembling l-analogues. Interestingly, changing the chirality of F yields very
      different nanostructures; nanotapes are observed for (D)VFF, twisted fibers for
      (D)FFV.

PMID- 22159640
TI  - Stem cells with fused gene expression of cytosine deaminase and interferon-beta
      migrate to human gastric cancer cells and result in synergistic growth inhibition
      for potential therapeutic use.
AB  - Genetically engineered stem cells (GESTECs) producing suicide enzymes and
      immunotherapeutic cytokines have therapeutic effects on tumors, and may possibly
      reduce the side effects of toxic drugs used for treatments. Suicide enzymes can
      convert non-toxic pro-drugs to toxic metabolites that can reduce tumor growth.
      Cytosine deaminase (CD) is a suicide enzyme that metabolizes a non-toxic pro
      drug, 5-fluorocytosine (5-FC), into the cytotoxic agent, 5-fluorouracil (5-FU).
      As an immunotherapeutic agent, human interferon-beta (IFN-beta) has anticancer
      effects. In this study, we used modified human neural stem cells (HB1.F3)
      expressing the Escherichia coli (E. coli) CD gene (HB1.F3.CD) or both the CD and
      human IFN-beta genes (HB1.F3.CD.IFN-beta) and evaluated their effectiveness on
      gastric carcinoma cells (AGS); migration of GESTECs to AGS was analyzed as well
      as formation of 5-FU and IFN-beta. Reverse transcription-polymerase chain
      reaction (RT-PCR) was used to confirm the expression of CD and IFN-beta genes in
      GESTECs along with confirming the production of chemoattractant molecules such as
      stem cell factor (SCF), CXCR4, c-Kit, vascular endothelial growth factor (VEGF)
      and VEGF receptor 2 (VEGFR2). In addition, by co-culturing GESTECs with AGS in
      the presence of 5-FC, we were able to confirm that cancer growth was inhibited,
      along with a synergistic effect when the CD and IFN-beta genes (HB1.F3.CD.IFN
      beta) were co-expressed. Indeed a marked anticancer effect was demonstrated when
      the CD and IFN-beta genes were expressed together compared to expression of the
      CD gene alone (HB1.F3.CD). According to a modified transwell migration assay, the
      migration of GESTECs toward AGS was confirmed. In conclusion, these data suggest
      potential application of GESTECs to gastric cancer therapy, due to a remarkable
      synergistic effect of CD and IFN-beta genes in the presence of 5-FC.
      Additionally, the tumor-selective migration capability in vitro suggests that
      GESTECs are a potential anticancer therapy candidate that may result in minimal
      side effects compared to the conventional chemotherapy.

PMID- 22159643
TI  - Open-ended TiO2 nanotubes formed by two-step anodization and their application in
      dye-sensitized solar cells.
AB  - We demonstrate a simple method to fabricate open-ended TiO(2) nanotube (NT) based
      dye-sensitized solar cells (DSSCs), where the NTs are attached to either TiO(2)
      nanorods (NRs) grown on fluorine-doped tin oxide (FTO) or FTO directly by
      nanoparticles (NPs). A completely hole-through TiO(2) NT layer is fabricated via
      a two-step anodization with heat treatment immediately after the first
      anodization. DSSCs with the open-ended NTs show better photovoltaic performance
      than those with close-ended NTs, due to the enhanced charge transport in the open
      ended structure. Under optimum conditions, DSSCs fabricated with the open-ended
      NT layer exhibit a short circuit current density (J(sc)) of 19.10 mA cm(-2), an
      open circuit voltage (V(oc)) of 0.68 V, a fill factor (FF) of 0.49, and a power
      conversion efficiency (eff) of 6.3%.

PMID- 22159642
TI  - On the page number of RNA secondary structures with pseudoknots.
AB  - Let S denote the set of (possibly noncanonical) base pairs {i, j } of an RNA
      tertiary structure; i.e. {i, j} ? S if there is a hydrogen bond between the ith
      and jth nucleotide. The page number of S, denoted pi(S), is the minimum number k
      such that Scan be decomposed into a disjoint union of k secondary structures.
      Here, we show that computing the page number is NP-complete; we describe an exact
      computation of page number, using constraint programming, and determine the page
      number of a collection of RNA tertiary structures, for which the topological
      genus is known. We describe an approximation algorithm from which it follows that
      omega(S) <= pi(S) <= omega(S) ?log n,where the clique number of S, omega(S),
      denotes the maximum number of base pairs that pairwise cross each other.

PMID- 22159644
TI  - [Impact of the fortification of food with folic acid on neural tube defects in
      Costa Rica].
AB  - OBJECTIVE: Evaluate the impact of the fortification of food with folic acid on
      prevalence trends for neural tube defects (NTD) and the infant mortality rate
      (IMR) associated with this disorder in Costa Rica. METHODS: The surveillance data
      from the Congenital Disease Registry Center and the Central American Population
      Center were analyzed. The neural tube defects considered were anencephaly, spina
      bifida, and encephalocele. The trends from 1987-2009, as well as the differences
      in prevalence and mortality rates prior to and up to 12 years after food
      fortification with folic acid, were examined (95% confidence interval [CI]). The
      contribution of fortification to the decrease in the overall IMR was determined.
      RESULTS: During 1987-1997, prior to the period of food fortification with folic
      acid, NTD prevalence was 12/10 000 births (95% CI: 11.1-12.8), whereas in 2009
      prevalence was 5.1/10 000 births (3.3-6.5). The IMR associated with NTD was
      0.64/1 000 births (46-0.82) in 1997 and 0.19/1 000 births (0.09-9.3) in 2009.
      There were significant decreases in the IMR associated with NTD and the
      prevalence of NTD: 71%, and 58%, respectively (P < 0.05). The overall IMR
      decreased from 14.2/1 000 births in 1997 to 8.84/1 000 births in 2009 (P < 0.05).
      The decrease in the IMR associated with NTD contributed to an 8.8% decrease in
      the overall IMR from 1997 to 2009. CONCLUSIONS: Food fortification with folic
      acid caused a decrease in NTD at birth and the IMR associated with this
      malformation during the 1997-2009 period. It also led to a decrease in the
      overall IMR. There is a temporal relationship between the introduction of
      fortification policies and the decrease in prevalence and mortality associated
      with NTD. This intervention should be promoted in Latin American and Caribbean
      countries where it has not yet been implemented.

PMID- 22159645
TI  - Brazilian experience with rapid monitoring of vaccination coverage during a
      national rubella elimination campaign.
AB  - OBJECTIVE: To describe an adapted version of the Pan American Health Organization
      (PAHO) methodology for rapid monitoring of vaccination coverage and its use as a
      supervisory tool to guide decision-making and strategies for end-stage
      vaccination activities ("mop-up" operations) following a six-week national
      rubella elimination campaign in Brazil. METHODS: Vaccination coverage assessments
      modeled on a variation of PAHO's rapid house-to-house coverage monitoring
      methodology were conducted by Brazilian municipalities following mass
      immunization of adults and adolescents from August to December 2008. Results of
      monitoring assessments conducted in 3 658 (65.7%) of 5 564 municipalities were
      reported to Brazil's National Immunization Program. RESULTS: Information on
      vaccination against rubella was obtained from more than 1.5 million Brazilians
      (2.1% of the 70.1 million people targeted for immunization) during vaccination
      coverage monitoring. According to the assessment data, vaccination targets of 95%
      coverage were reached in 2 175 (59.5%) of the 3 658 municipalities that reported
      results. The percentage of municipalities that reached coverage targets was lower
      than administrative coverage estimates (number of vaccine doses administered
      divided by the immunization target population). These results informed targeted
      "mop-up" campaigns to reach unvaccinated populations. CONCLUSIONS: Rapid coverage
      monitoring implemented at the local level proved useful for deciding when to
      conclude vaccination activities and where to focus additional efforts to achieve
      desired coverage.

PMID- 22159646
TI  - [Child mortality from cancer in Colombia, 1985-2008].
AB  - OBJECTIVE: Determine the magnitude of child mortality from cancer in Colombia and
      evaluate the trends in its evolution from 1985 to 2008. METHODS: Mortality in the
      Colombian population aged 0-14 years from cancer in any site (e.g., leukemia,
      malignant tumors of the central nervous system (CNS), non-Hodgkin's lymphoma,
      Hodgkin's lymphoma, bone tumors, kidney tumors) during this period was analyzed.
      The mean change in the variations of cancer mortality trends in this age group
      was calculated. RESULTS: Deaths from cancer accounted for 3.5% of mortality in
      children under 15 years of age. During the periods 1985-1989 and 2005-2008 there
      was a decrease in mortality from cancer in both sexes, with figures dropping from
      54.4 deaths per million to 44.8 deaths per million in boys and from 40.9 deaths
      per million to 37.9 deaths per million in girls. There was a statistically
      significant decrease in leukemia- and lymphoma-related mortality, whereas
      mortality associated with cancers of the CNS increased significantly.
      CONCLUSIONS: In spite of slight downward trends in mortality from leukemia and
      non-Hodgkin's lymphoma, childhood cancer mortality rates in Colombia remain high.
      Significant work on treatments for childhood cancer is required to obtain greater
      success.

PMID- 22159647
TI  - [Influence of family environment and social group on smoking among Brazilian
      youth aged 15 to 24 years].
AB  - OBJECTIVE: To estimate the prevalence of smoking among Brazilian youth, examining
      individual, family, and social group factors associated with this habit. METHODS:
      Data from youth aged 15 to 24 years living in 17 Brazilian state capitals and the
      Federal District, obtained from the Household Survey on Risk Factors for Chronic
      Diseases and Reported Morbidity carried out in 2002 and 2003 by the National
      Cancer Institute was analyzed. Individual variables (sex, age, schooling, alcohol
      consumption, self-rated health, physical activity, current school attendance),
      family variables (age and education of head of household and father, mother, or
      sibling smoking), and social group variables (best friend smoking, most friends
      smoking, boyfriend/girlfriend smoking) were analyzed. Generalized estimating
      equations (GEE) approach to evaluate the factors associated with smoking were
      used. RESULTS: Considering the effect of the sampling design, smoking prevalence
      was 12.8%, ranging from 6.8% in Aracaju to 24.1% in Porto Alegre. The following
      factors were predictors of smoking: male sex, older age, less schooling, not
      attending school at the time of the survey, poorer health perception, and alcohol
      consumption. Peer smoking (friends or boyfriend/girlfriend) and smoking among
      family members (father/mother or sibling) were associated with smoking. There was
      an effect of parental birth cohort on smoking, with a higher prevalence of
      smoking among youth whose parents were born in the 1930s. CONCLUSIONS: Individual
      characteristics and the influence of peers and family were relevant for smoking
      by the youth. Increasing the dialogue among teenagers, school, schoolmates,
      friends, and parents could lead to a reduction of substance use among youth.

PMID- 22159648
TI  - [Epidemiology and registry of congenital heart disease in Costa Rica].
AB  - OBJECTIVE: Characterize the population of children born with congenital heart
      disease (CHD) in Costa Rica and evaluate the country's registry processes.
      METHODS: Exploratory observational study that included all children with CHD
      diagnosed at the National Children's Hospital between 1 May 2006 and 1 May 2007.
      Considering children under 1 year of age and their respective birth cohort,
      prevalence was estimated by sex, type of heart disease, age at diagnosis,
      maternal age, habitual residence, and associated extracardiac malformations, with
      95% confidence intervals (95% CI). The data was compared with those of the
      Congenital Disease Registry Center (CREC). RESULTS: During the period studied,
      534 cases with CHD were diagnosed. There were 473 cases in children under 1 year
      of age in a birth cohort of 77 140 children. Prevalence was 0.6% (95% CI: 0.5
      0.7). Based on CREC data, it was demonstrated that 71% of the cases were not
      detected at birth. The average age of diagnosis in infants under 1 year of age
      was 46.6 days. There were no differences by sex. Prevalence of CHD in children of
      mothers aged 35 years or over was significantly higher. However, when chromosomal
      abnormalities were excluded, the risk was no longer statistically significant.
      The provinces in the country with maritime ports were the areas with the highest
      risk in children of adolescent mothers. The most common CHDs were ventricular and
      atrial septal defects, patent ductus arteriosus, pulmonary valve stenosis,
      atrioventricular septal defects, coarctation of the aorta, and tetralogy of
      Fallot. Thirty-four percent of the cases of CHD were multiple, 11.2% were
      associated with chromosomal abnormalities, and 19% had associated congenital
      malformations. CONCLUSIONS: CHD prevalence in Costa Rica is within the range
      reported globally. Significant underreporting of CHD was found in the CREC,
      primarily due to the age criteria applied. The results suggest that maternal age
      (under 20 and over 34) is a factor associated with CHD.

PMID- 22159649
TI  - Bioelectrical impedance values among indigenous children and adolescents in Rio
      Grande do Sul, Brazil.
AB  - OBJECTIVE: To describe the nutritional status of indigenous children and
      adolescents in Rio Grande do Sul, Brazil, through bioelectrical values, and to
      compare the nutritional classifications of the anthropometric method to those of
      the body composition method. METHODS: A cross-sectional survey was conducted of 3
      204 subjects at 35 schools in the 12 Kaingang indigenous lands of Rio Grande do
      Sul, Brazil. Following World Health Organization recommendations, the weight and
      height (H) of each subject was measured twice and the body mass index/age (BMI/A)
      was classified. Body composition was assessed by Bioelectrical Impedance Vector
      Analysis (BIVA). Resistance (R) and reactance (Xc) were estimated using a
      bioelectrical impedance analyzer. Divergences between these two methods were
      performed on RXc graph. RESULTS: Of the sample, 56.8% were adolescents and 50.6%
      were males. The mean values of phase angle were higher in adolescents, in males,
      and in individuals overweight by BMI/A. Mean values of R, Xc, R/H, and Xc/H were
      higher among children and among those with BMI/A < +2 z scores. Divergences in
      overweight classification were: male children, 94.6%; male adolescents, 77.1%;
      female children, 85.4%; and female adolescents, 94.8%. CONCLUSIONS: The mean
      values of bioelectrical measures observed among the Kaingang children and
      adolescent were similar to those found for different populations in other
      studies. For both gender and age groups, differences were observed between
      nutritional classifications by BMI/age and by BIVA. These results reinforce the
      importance of employing multiple techniques, such as anthropometry and BIVA, when
      conducting nutritional assessments of a population.

PMID- 22159650
TI  - [Prevalence of bacterial vaginosis in Chilean sex workers].
AB  - OBJECTIVE: To determine the prevalence of bacterial vaginosis (BV) in Chilean sex
      workers and relate the findings to sociodemographic, sexual, and clinical
      variables. METHODS: A sample of 379 sex workers seen in Chilean Sexual Health
      Monitoring and Care Units for check-ups was studied. All of them were interviewed
      to obtain their sociodemographic and sexual history. A clinical examination was
      performed that included the characteristics of vaginal discharge, pH, and amine
      test. A vaginal sample was taken for Gram stain. The Nugent criteria were used
      for the diagnosis of BV. The data was analyzed with EPI-INFO 3.4.1 and BioStat,
      using a degree of significance of P < 0.005. RESULTS: BV prevalence was 69.1%.
      The syndrome was not associated with the sociodemographic variables, age or
      education. BV was less common in women (married or unmarried) who lived with
      their partners than in single women (P < 0.001). There were no sexual variables
      associated with BV, whereas use of intrauterine devices was related (P < 0.0001).
      The presence of vaginal discharge, abnormal vaginal pH, and positive amine test
      were associated with infection (P < 0.0001). CONCLUSIONS: Like other studies
      conducted in different countries, this study observed that Chilean sex workers
      have a high prevalence of BV, with greater risk for women who use IUDs for birth
      control or women (married or unmarried) who do not live with their partners.

PMID- 22159651
TI  - [Nutrition and health in children from former slave communities (quilombos) in
      the state of Alagoas, Brazil].
AB  - OBJECTIVE: To describe the nutrition and health status of children aged 6 to 59
      months from 39 former slave communities in the state of Alagoas. METHODS: Data on
      anthropometric, demographic, socioeconomic, and health variables were collected
      for this cross-sectional study. Deficits in weight-for-age (WFA), weight-for
      height (WFH), and height-for-age (HFA) were defined as a Z score < -2. Overweight
      was defined as a Z score > 2 for WFH. The 2006 World Health Organization growth
      standards were used as reference. Anemia was diagnosed based on hemoglobin levels
      (HemoCue) < 11 g/dL. RESULTS: We assessed 973 children (50.4% boys). Most
      families (60.8%) belonged to social class E (lowest), and most (76.0%) were
      assisted by the federal welfare program Bolsa Familia. Heads of family had < 4
      years of schooling (75.9%), and more than 5 people lived in the house in 57.1% of
      the households. The prevalence of WFA, WFH, and HFA (stunting) deficits and
      overweight was, respectively, 3.4, 2.0, 11.5, and 7.1%. Anemia was diagnosed in
      52.7% of the children, without differences between the stunting and overweight
      groups (P = 0.43). CONCLUSIONS: Stunting, an indicator of chronic malnutrition,
      was the most prevalent anthropometric deviation, followed by overweight, despite
      the disadvantaged socioeconomic profile. Anemia was a severe problem, affecting
      children with both stunting and overweight. Taken together, these findings
      suggest that the human right to adequate food is not guaranteed for the children
      from former slave communities from Alagoas. Therefore, the government should take
      the necessary measures to revert this situation.

PMID- 22159652
TI  - [Assessment of core capacities for enforcement of the International Health
      Regulations at points of entry in Uruguay].
AB  - OBJECTIVE: To describe the characteristics and results of the assessment of core
      capacities for enforcement of the International Health Regulations (IHR) at
      points of entry in Uruguay through simultaneous application of the World Health
      Organization (WHO) and MERCOSUR instruments, and indicate the strengths and
      weaknesses identified in both instruments when applied in the field. METHODS: A
      descriptive cross-sectional study was conducted through the application of the
      WHO and MERCOSUR instruments to assess core capacities for the enforcement of the
      IHR. Two points of entry (POE 1 and 2) were selected as a convenience sample
      because they had the highest volume of passenger and goods traffic in the
      country. Both instruments were characterized individually and qualitatively in
      terms of strengths and weaknesses. RESULTS: The average values for the
      implementation of core capacities were 69% (WHO) and 67.4% (MERCOSUR) for POE 1
      and 68% (WHO) and 63.9% (MERCO-SUR) for POE 2. The average differences recorded
      between the instruments were 1.6% for POE 1 and 4.1% for POE 2. Both instruments
      examined nonmeasurable factors that are subject to the evaluator's judgment,
      without using operational definitions of the relevant variables. CONCLUSIONS:
      Simultaneous application of the WHO and MERCOSUR instruments yielded similar
      levels of implementation at the two points of entry assessed. The assessment
      processes of the two instruments would be enhanced by capitalizing on each
      other's strengths and addressing the weaknesses observed and recorded in this
      study.

PMID- 22159653
TI  - Structural actions toward HIV/AIDS prevention in Cartagena, Colombia: a
      qualitative study.
AB  - OBJECTIVE: To obtain a thorough understanding of the complexity and dynamics of
      the social determination of HIV infection among inhabitants of Cartagena,
      Colombia, as well as their views on necessary actions and priorities. METHODS: In
      a five-year ethnography of HIV/AIDS in collaboration with 96 citizens of
      Cartagena, different methods and data collection techniques were used. Through 40
      in-depth interviews and 30 life histories of inhabitants, the scenario of HIV
      vulnerability was summarized in a diagram. This diagram was evaluated and
      complemented through group discussions with key representatives of local
      governmental and nongovernmental organizations and with people who were
      interested in the epidemic or affected by it. RESULTS: The diagram illustrates
      the dynamic and complex interrelationships among structural factors (i.e., social
      determinants) of HIV infection, such as machismo; lack of work, money, and social
      services; local dynamics of the performance of the state; and international
      dynamics of the sexual tourism industry. On the basis of the diagram, groups of
      key representatives proposed prioritizing structural actions such as reducing
      socioeconomic inequalities and providing access to health care and education.
      CONCLUSIONS: The social determinants displayed in the diagram relate to historic
      power forces that have shaped vulnerable scenarios in Cartagena. Collaboration
      between participants and researchers generates conceptual frameworks that make it
      possible to understand and manage the complexity of HIV's social determination.
      This way of understanding effectively connects local inequalities with
      international flows of power such as sexual tourism and makes evident the
      strengths and limitations of current approaches to HIV prevention.

PMID- 22159654
TI  - [Depression and self-perceived burden of care by hemodialysis patients and their
      caregivers].
AB  - OBJECTIVE: To determine the depressive symptoms, perceived social support, and
      self-perceived burden in chronic hemodialysis (CHD) patients; identify depressive
      symptoms and degree of fatigue in caregivers of CHD patients; evaluate-in
      patients-the association between self-perceived burden and perceived social
      support, and between self-perceived burden and depressive symptoms; and evaluate
      in caregivers-the relationship between the number of years of care and the degree
      of fatigue reached. METHODS: A sample of 162 patient-caregiver pairs was selected
      in which an adapted version of the Multidimensional Scale of Perceived Social
      Support, along with the Self-perceived Burden Scale, the Center for Epidemiologic
      Studies Depression Scale, and the Fatigue Severity Scale were applied. The
      instruments were administered to patients by trained research assistants and, in
      the case of the caregivers, were self-administered. RESULTS: Forty percent of the
      patients were women, with an average age of 56 +/- 14.9 years, whereas 75% of the
      primary caregivers were female spouses, with an average age of 50 +/- 16.1 years.
      It was observed that the patients (40.74%) as well as the primary caregivers
      (43.82%) had depressive symptoms. A positive association (r = 0.43, P < 0.001)
      was found between self-perceived burden and the presence of depressive symptoms
      in patients. CONCLUSIONS: The majority of the primary caregivers were women and
      relatives of the patients. They perceived themselves as fatigued with care, as
      did the patients themselves. The presence of depressive symptoms was similar in
      patients and caregivers. There was a statistically significant association
      between self-perceived burden and the presence of depressive symptoms in
      patients.

PMID- 22159655
TI  - [Evidence of the contribution of elderly support programs to healthy aging in
      Brazil].
AB  - OBJECTIVE: To search the literature for evidence of the contribution of elderly
      health programs to the process of healthy aging in Brazil. METHODS: The databases
      Science Direct, SciELO, LILACS, IBECS, the Cochrane Library, and MEDLINE were
      searched to find articles focusing on initiatives developed for the elderly
      population and to promote healthy aging, providing a multidimensional evaluation
      of the quality of life of the elderly, and covering aspects relating to specific
      health promotion practices. The initiatives were considered effective if the
      following criteria were met: having goals that included the improvement of health
      and well-being, having a focus on holistic health, using empowerment as a central
      mechanism to improve health, and meeting the prerequisites for health and
      developing actions in the priority areas described in the Ottawa Charter.
      RESULTS: Ten articles referring to five elderly health promotion programs in
      Brazil were identified. All the programs met the efficacy criteria, and included
      elements that promoted healthy aging through characteristics that fostered the
      insertion of the elderly in society through the creation of a support environment
      for the prevention of injury, increase in functional capacity, and improvement of
      quality of life. CONCLUSIONS: Studies are required to produce scientific evidence
      on the efficacy, efficiency, and effectiveness of elderly health programs to
      determine the value of these actions to promote healthy aging.

PMID- 22159656
TI  - Prospective registration and results disclosure of clinical trials in the
      Americas: a roadmap toward transparency.
AB  - The objective of this article is to propose a roadmap toward transparency of
      clinical trials in the Americas by their prospective registration and results
      disclosure. This will broaden access to more complete and accurate data and
      facilitate evidence-informed decision-making and participation in research.
      Consequently, it should have a positive impact on people's health and should
      promote trust in health research. Existing initiatives were identified,
      registration of trials was analyzed following the World Health Organization (WHO)
      standards on trial registration, and a roadmap is proposed to address the gaps in
      advancing transparency. The analysis shows that, in spite of numerous regional
      and country initiatives, clinical trials taking place in nonEnglish-speaking
      parts of the Americas are underregistered. A roadmap is proposed to enhance
      research governance and good research practice by improving the transparency of
      clinical trials. The proposed roadmap includes strategies for implementing WHO
      international standards for trial registration, for developing international
      standards of public disclosure of trial results, and for a potential role of the
      Pan American Health Organization.

PMID- 22159657
TI  - Effect of rat brain tissue extracts on osteoblast proliferation and
      differentiation.
AB  - PURPOSE: The reason for enhanced fracture healing in traumatic brain injury
      patients is not clearly understood. It is possible that factors inherent in the
      brain passing through the blood-brain barrier to the peripheral circulation, or a
      disruption of central nervous system (CNS) control of the sympathetic nervous
      system (SNS), stimulates the process of fracture healing. METHODS: In this study,
      we assessed proliferation [using the 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assay] and differentiation [using alkaline
      phosphatase (ALP)] in rat osteoblasts incubated with gray matter or other tissue
      extracts with and without the addition of an alpha- or beta-adrenergic receptor
      blocker (phentolamine or propranolol). RESULTS: Gray matter extract from normal
      brain caused a dose-dependent increase in osteoblast proliferation and
      differentiation. Serum from normal rats enhanced differentiation but not
      proliferation. Alpha-receptor blockade had no effect on proliferation or
      differentiation. Beta-receptor blockade caused a partial, but statistically
      significant, decrease in gray matter stimulation of osteoblast differentiation.
      CONCLUSION: The results of this study indicate that gray matter extract from
      normal brain increases osteoblast proliferation and differentiation and that beta
      receptors may be involved in differentiation under these conditions.

PMID- 22159658
TI  - Postoperative disc space infection after discectomy: a report on thirty-five
      patients.
AB  - PURPOSE: The focus of this study was to analyse the patient with disc space
      infection and the need for re-exploration. METHOD: Thirty-five patients were
      analysed within the period from April 1992 and May 2011. The diagnosis was
      confirmed by the cardinal clinical features, raised erythrocyte sedimentation
      rate [ESR], raised C-reactive protein and MRI findings. All received 500-mg
      intravenous amikacin and one gram ceftriaxone at the time of anaesthetic
      induction and six hours after surgery. RESULTS: Age range was between 25-62
      years. The appearance of symptoms was between four days and three weeks. Nine
      patients had silent chronic urinary tract infection. Twenty-nine patients had re
      exploration while the others did well on conservative treatment. Neurological
      deficit was not recorded. All recovered well within six to nine months.
      CONCLUSION: Re-exploration is recommended if no response is achieved after four
      day's conservative treatment for or if the patient's condition is critical.

PMID- 22159659
TI  - Operative versus nonoperative treatment for acute Achilles tendon rupture: a meta
      analysis based on current evidence.
AB  - PURPOSE: The aim of this study was to evaluate, in a meta-analysis, the clinical
      effectiveness of operative treatment for acute Achilles tendon rupture (AATR)
      compared with nonoperative treatment. METHODS: We systematically searched six
      electronic databases (Medline, Embase, Clinical Ovid, BIOSIS and Cochrane
      registry of controlled clinical trials) to identify randomised controlled trials
      (RCTs) in which operative treatment was compared with nonoperative treatment for
      AATR from 1980 to 2011. Trial quality was assessed using the modified Jadad
      scale. The data was using fixed-effects and random-effects models with mean
      differences and risk ratios for continuous and dichotomous variables,
      respectively. RESULTS: Ten RCTs with a total of 894 patients were screened. The
      results showed that operative was superior to nonoperative treatment regarding
      lower risk of re-rupture (P = 0.002) and shorter time for sick leave (P = 0.009)
      but inferior to nonoperative treatment regarding complication risks (P = 0.004).
      No significant difference was identified between the two methods regarding the
      number of patients who successfully returned to pre-injury sports (P = 0.30).
      Subgroup analyses revealed significant differences in relation to scar adhesion
      (P < 0.00001), superficial infection (P = 0.05), and sensibility disturbance (P =
      0.0003). However, no significant differences were found between the two
      interventions in relation to deep infection (P = 0.22), deep vein thrombosis
      (DVT) (P = 0.14), and extreme Achilles tendon lengthening (P = 0.31). Little
      consensus was obtained in the functional recovery from current trials as a result
      of an inconsistent assessment system. CONCLUSIONS: Compared with conservative
      treatment, operative treatment can effectively reduce the risk of re-rupture but
      increase the probability of complications. The increased complication risk may be
      associated with open repair surgery. However, no sufficient evidence is available
      from current studies to support the belief that operation may lead to better
      functional recovery.

PMID- 22159661
TI  - Directed evolution of a highly active Yersinia mollaretii phytase.
AB  - Phytase improves as a feed supplement the nutritional quality of phytate-rich
      diets (e.g., cereal grains, legumes, and oilseeds) by hydrolyzing indigestible
      phytate (myo-inositol 1,2,3,4,5,6-hexakis dihydrogen phosphate) and increasing
      abdominal absorption of inorganic phosphates, minerals, and trace elements.
      Directed phytase evolution was reported for improving industrial relevant
      properties such as thermostability (pelleting process) or activity. In this
      study, we report the cloning, characterization, and directed evolution of the
      Yersinia mollaretii phytase (Ymphytase). Ymphytase has a tetrameric structure
      with positive cooperativity (Hill coefficient was 2.3) and a specific activity of
      1,073 U/mg which is ~10 times higher than widely used fungal phytases. High
      throughput prescreening methods using filter papers or 384-well microtiter plates
      were developed. Precise subsequent screening for thermostable and active phytase
      variants was performed by combining absorbance and fluorescence-based detection
      system in 96-well microtiter plates. Directed evolution yielded after mutant
      library generation (SeSaM method) and two-step screening (in total ~8,400 clones)
      a phytase variant with ~20% improved thermostability (58 degrees C for 20 min;
      residual activity wild type ~34%; variant ~53%) and increased melting temperature
      (1.5 degrees C) with a slight loss of specific activity (993 U/mg).

PMID- 22159660
TI  - The effect of acetylated xylan and sugar beet pulp on the expression and
      secretion of enzymes by Penicillium purpurogenum.
AB  - Sugar beet pulp is a natural carbon source composed mainly of pectin and
      cellulose, which is utilized and degraded by the ascomycete Penicillium
      purpurogenum. The fungus also grows on and degrades acetylated xylan which lacks
      cellulose and pectin. Both carbon sources have been used in our laboratory to
      grow the fungus and to purify different enzymes secreted to the medium. The
      enzymes involved in the complex process of degradation of these carbon sources by
      the fungus have been explored previously under non-denaturing conditions;
      multienzyme complexes were separated and some subunits identified by Western
      blots and mass spectrometry. In this work, proteomic profiles show that the
      secretome is composed of numerous proteins varying in pI and molecular weight.
      Some enzymes are common to both growth conditions, while others are specific for
      each carbon source. The results show that the carbon sources utilized exert
      strong regulatory control over the proteins secreted. This is the first secretome
      study from a lignocellulolytic Penicillium.

PMID- 22159662
TI  - Low tolerability of carbamazepine in psychiatric patients may restrict its
      clinical usefulness.
AB  - There are reports of prophylactic efficacy of carbamazepine (CBZ) in manic depres
      sives when compared with placebo and chlorpromazine. Following a successful open
      pilot study by one of the authors, an attempt was made to compare carbamazepine
      and lithium carbonate in a double-blind, crossover trial, each patient being
      assigned to take each drug for 9 months in random order. However, of the first 14
      patients to take carbamazepine four were withdrawn because of drug rashes and
      another two because of other adverse effects. The trial was discontinued, and a
      casenotes survey of 50 consecutive psychiatric patients who had been prescribed
      carbamazepine for mood disorders was then carried out, to establish the
      tolerability of the drug in clinical practice. Of these, 22 per cent had suffered
      dizziness, nausea or unsteadiness despite slow introduction of doses. Drug rashes
      occurred in 16 per cent of patients within the two weeks of starting treatment. A
      further 14 per cent had other unwanted effects. In total, 36 per cent of the
      patients had the drug stopped because of adverse effects. With regard to
      efficacy, in those taking the drug for more than 4 weeks, clinicians reported a
      definite or probable advantageous effect in 62 per cent of the sample, definite
      or probable lack of effect in 19 per cent and no opinion in 19 per cent. This low
      tolerability is not in accordance with previous reports of 2-6 per cent incidence
      of drug rashes and 10 per cent overall intolerance in neurological patients. We
      conclude that tolerability is a major drawback to the use of carbamazepine in
      some groups of psychiatric patients, although all the side- effects were
      reversible. However, clinical impressions suggested that in a number of patients
      no other therapeutic strategy was as effective in preventing mood swings.

PMID- 22159663
TI  - Evidence that background GABAergic tone and possible ligand release may alter the
      action of the 'neutral' benzodiazepine-receptor antagonist, Ro 15-1788, in
      hypothalamic self-stimulation.
AB  - Upward or downward shifts in the level of brain GABAergictransmission have been
      held to be necessary and sufficient to promote release of endogenous ligands
      ('endocoids') for the benzodiazepine (BZD) recognition site. To investigate this
      possibility, variable-interval self-stimulation performance was used to monitor
      'intrinsic' benzodiazepine-like and anti- benzodiazepine activity by the
      'neutral' benzodiazepine-receptor antagonist, Ro 15-1788 (flumazenil) (10 or 30
      mg/kg intraperitoneally). Rats were pretreated with either a GABA synthesis
      blocking agent (isoniazid, 130 mg/kg subcutaneously), or with a GABA agonist
      (progabide, 30 or 100 mg/kg intraperitoneally). The lower dose of Ro 15-1788 (10
      mg/kg), without pretreatment, did not affect self-stimulation; higher doses (30
      mg/kg) caused a brief (<20 min) depression. Isoniazid (130 mg/kg) depressed self
      stimulation, but did not modify the activity of Ro 15-1788. In rats pretreated
      with progabide (100 mg/kg), low doses of Ro 15- 1788 (10 mg/kg) that were
      previously without effect now caused a sharp fall in responding. These findings
      can be interpreted as showing that even low doses of Ro 15-1788 may affect self
      stimulation under certain conditions, and that they do so by competing with an
      endogenous ligand for the benzodiazepine site, released by upward shifts in
      GABAergic activity. Alternative explanations in terms of altered receptor
      function seem less feasible. The results imply that the action of the endogenous
      ligand would not resemble that of a typical benzodiazepine, but that of an
      inverse agonist (that is, proconflict and proconvulsant); this conclusion agrees
      with recent biochemical evidence.

PMID- 22159664
TI  - Corticotropin-releasing factor immunoreactivity in post-mortem brain from
      depressed suicides.
AB  - Corticotropin-releasing factor immunoreactivity (CRF-I) was measured in cortical
      brain tissue obtained at post-mortem from 12 suicide victims with clear evidence
      of depressive illness and 12 age-matched and sex-matched control subjects dying
      by natural causes. There were no significant differences in mean CRF-I
      concentrations in frontal, temporal, motor and parietal cortex between the total
      suicide group, or the eight drug-free suicides and their matched controls. These
      findings suggest that cortical CRF-I concentrations are unaltered in depressive
      illness and are discussed in relation to recent reports of elevated CRF-I con
      centrations in the cerebrospinal fluid of depressed patients.

PMID- 22159665
TI  - Effects of caffeine on vigilance and other performance tests in normal subjects.
AB  - In two randomized double-blind crossover studies, 8 and 10 healthy volunteers
      took either 200 mg caffeine or placebo. Objective and subjective measures of
      caffeine effects were carried out over the following 1-3.5 h. Auditory vigilance,
      a test lasting 1 h, showed significantly better performance on caffeine than on
      placebo. In the second study, this effect was only apparent in the second half of
      the test. Of the shorter objective tests used, only finger tapping showed a
      significant effect of caffeine, the rate of tapping over 1 min being increased.
      The subjective assessments showed increased interest and alertness in the
      caffeine session. Reliable detection of the effects of mild stimulant drugs using
      objective measures may require the use of tests of long duration.

PMID- 22159666
TI  - Mediation by serotonin of the antiaversive effect of zimelidine and propranolol
      injected into the dorsal midbrain central grey.
AB  - Previously reported results indicate that serotonin (5-HT) inhibits the neural
      sub strate of aversion in the dorsal midbrain central grey (DCG) of the rat. In
      addition, the present results show that microinjection of the 5-HT uptake
      inhibitor zimelidine (100 nmol) into the DCG of rats with chronically implanted
      chemitrodes raised the threshold of aversive electrical stimulation. This
      antiaversive effect of zimelidine was antagonized by pretreatment with the 5
      HT(2) receptor blocker ritanserin (10 nmol), also microinjected into the DCG. In
      contrast, the antiaversive effect of the benzodiazepine agonist midazolam (40
      nmol) was unaffected by ritanserin. Propranolol (2.2, 4.4 and 8.8 nmol) raised
      the aversive threshold in a dose-depen dent way following its injection into the
      DCG. The antiaversive effect of 4.4 nmol of propranolol was antagonized by
      previous administration of ritanserin (10 nmol). Moreover, combined
      administration of zimelidine (100 nmol) followed by propranolol (4.4 nmol) caused
      an anti aversive effect which was equivalent to the sum of the effect of each
      drug alone. These results indicate that the antiaversive effect of
      intracerebrally injected zimelidine and propranolol is mediated by endogenous 5
      HT, through activation of 5-HT(2) receptors.

PMID- 22159667
TI  - Measures of anxiety and stress in the rat following chronic treatment with
      yohimbine.
AB  - Yohimbine (2.5 and 5 mg/kg) was investigated in two animal tests of anxiety and
      on baseline corticosterone plasma concentrations, following both acute and
      chronic administration. Acute treatment with yohimbine produced the following
      effects: a reduction in the percentage of total arm entries made onto the open
      arms and in the percentage of time spent on the open arms of an elevated plus
      maze (indicating anxiogenic properties), an increase in baseline plasma
      corticosterone concentrations, and a reduction in locomotor activity (recorded in
      the social interaction test). No significant effects were observed on anxiety
      levels as measured by the social interaction test. Following chronic treatment,
      we saw no evidence for sensitization to the effects of yohimbine.

PMID- 22159668
TI  - Relationship between extrapyramidal symptoms and serum anticholinergic levels in
      treated chronic schizophrenics.
AB  - Serum anticholinergic levels were measured by radioreceptor assay (RRA) in
      schizophrenic patients treated for drug-induced Parkinsonism; 68 patients
      stabilized on a single neuroleptic and an anticholinergic antiparkinsonian agent
      (benzhexol, benztropine or procyclidine) were assessed using the extrapyramidal
      side effects (EPS) scale prior to each blood sampling. Serum anticholinergic
      levels showed a significant inverse correlation with EPS but did not appear to be
      dose-related in any of the three anticholinergic drug groups. Percentage binding
      to proteins was significantly less with benztropine than either benzhexol or
      procyclidine. Serum-free anticholinergic levels correlated significantly with
      total serum levels in the benzhexol and procyclidine groups but not in the
      benztropine group. At serum levels above 4.5 pmol/ml atropine equivalents, EPS
      was significantly less than at levels below that. We discuss the implications of
      this finding and suggest practical clinical applications of measurement of serum
      anticholinergic levels. Serum neuroleptic and serum prolactin levels did not
      correlate with either dose or serum level of anticholinergics.

PMID- 22159669
TI  - Effects of the putative 5-HT agonist 5-OH-DPAC on male rat sexual behaviour: a
      comparison with effects produced by 8-OH-DPAT and buspirone.
AB  - The new 5-HT agonist 5-hydroxy-3-(di-n-propylamino)chroman (5-OH-DPAC), 0.025-3.2
      mg:kg(-1), produced a marked facilitation of male rat sexual behaviour,
      characterized by a decrease in the number of intromissions preceding ejaculation
      and in time to ejaculation. The compound is in this regard as efficacious as 8-OH
      DPAT, but about 3 times less potent. Buspirone, 2-4 mg:kg(-1), also produced a
      facilitation of the male rat sexual behaviour, but with less efficacy and with
      considerably less potency than either 8-OH-DPAT or 5-OH-DPAC. In the experiment
      where 5-OH-DPAC and 8-OH-DPAT were directly compared, the display of flat body
      posture was recorded immediately before the sexual behaviour observations. These
      observations indicate: (1) that the occurrence of this behavioural syndrome does
      not interfere with the performance of sexual behaviour in 8-OH-DPAT treated rats;
      and (2) at doses where the male rat sexual behaviour was affected to the same
      degree by 8-OH-DPAT and 5-OH- DPAC, only the former compound produced the flat
      body posture.

PMID- 22159670
TI  - The application of single-crystal-to-single-crystal transformation towards
      adjustable SMM properties.
AB  - Reversible single-crystal-to-single-crystal transformation (SCSC) was for the
      first time observed between 4f-based molecular magnets.

PMID- 22159671
TI  - Prevention of disuse osteoporosis in rats by Cordyceps sinensis extract.
AB  - Cordyceps sinensis has been known as a traditional medicine in China, and C.
      sinensis plus strontium could prevent osteoporosis in ovariectomized rats. The
      present study shows that daily oral administration of C. sinensis at higher doses
      in adult hind limb suspension rats can prevent disuse-induced bone loss and
      deterioration of trabecular microarchitecture. INTRODUCTION: Cordyceps sinensis
      induces estradiol production and prevents osteoporosis in ovariectomized rats.
      This study was to examine whether C. sinensis can prevent disuse-induced
      osteoporosis. METHODS: Rats were randomly divided into six groups, and five
      groups were treated with hind limb suspension (HLS). One HLS group received
      alendronate (2.0 mg/kg/day) orally, and to the three other HLS groups to each
      group, a different amount of C. sinensis (100, 300, and 500 mg/kg/day) was orally
      administered for 8 weeks before and after HLS. The remaining HLS group was set as
      a control without treatment. Each group consisted of 10 males and females. The
      body weights, biochemical parameters in serum and urine, bone mineral density
      (BMD), bone mineral content (BMC), mechanical testing, and bone microarchitecture
      were examined. RESULTS: Treatments with higher C. sinensis dosage (300 and 500
      mg/kg/day) or alendronate had a positive effect on body weights, mechanical
      strength, BMD, and BMC compared to the other HLS groups. C. sinensis decreased
      markers of bone turnover dose dependently and increased the osteocalcin levels in
      HLS rats. The result of micro-CT analysis from the L4 vertebra showed that C.
      sinensis (500 mg/kg) significantly prevented the reduction of the bone volume
      fraction, connectivity density, trabeculae number, and thickness as well as
      improved the trabeculae separation and structure model index in HLS rats.
      CONCLUSIONS: The present study demonstrates that administration of C. sinensis at
      higher doses over an 8-week period can prevent the disuse osteoporosis in rats.
      It implies that C. sinensis might be an alternative therapy for prevention of
      disuse-induced osteoporosis also in humans.

PMID- 22159672
TI  - The effect of teriparatide compared with risedronate on reduction of back pain in
      postmenopausal women with osteoporotic vertebral fractures.
AB  - The effect of teriparatide and risedronate on back pain was tested, and there was
      no difference in the proportion of patients experiencing a reduction in back pain
      between groups after 6 or 18 months. Patients receiving teriparatide had greater
      increases in bone mineral density and had fewer vertebral fractures.
      INTRODUCTION: This study aimed to understand the effect of teriparatide in
      reducing back pain in patients with prevalent back pain and vertebral fracture
      compared to risedronate. METHODS: In an 18-month randomized, double-blind, double
      dummy trial, we investigated the effects of teriparatide (20 MUg/day) vs.
      risedronate (35 mg/week) in postmenopausal women with back pain likely due to
      vertebral fracture. The primary objective was to compare the proportion of
      subjects reporting >=30% reduction in worst back pain severity from baseline to 6
      months as assessed by a numeric rating scale in each treatment group. Pre
      specified secondary and exploratory outcomes included assessments of average and
      worst back pain at additional time points, disability and quality of life, bone
      mineral density, incidence of fractures, and safety. RESULTS: At 6 months, 59% of
      teriparatide and 57% of risedronate patients reported >=30% reduction in worst
      back pain and there were no differences between groups in the proportion of
      patients experiencing reduction in worst or average back pain at any time point,
      disability, or quality of life. There was a greater increase from baseline in
      bone mineral density at the lumbar spine (p = 0.001) and femoral neck (p = 0.02)
      with teriparatide compared to risedronate and a lower incidence of vertebral
      fractures at 18 months (4% teriparatide and 9% risedronate; p = 0.01). Vertebral
      fractures were less severe (p = 0.04) in the teriparatide group. There was no
      difference in the overall incidence of adverse events. CONCLUSIONS: Although
      there were no differences in back pain-related endpoints, patients receiving
      teriparatide had greater skeletal benefit than those receiving risedronate.

PMID- 22159673
TI  - Retinal ganglion cell layer thickness and local visual field sensitivity in
      glaucoma.
AB  - OBJECTIVE: To compare loss in sensitivity measured using standard automated
      perimetry (SAP) with local retinal ganglion cell layer (RGC) thickness measured
      using frequency-domain optical coherence tomography in the macula of patients
      with glaucoma. METHODS: To compare corresponding locations of RGC thickness with
      total deviation (TD) of 10-2 SAP for 14 patients with glaucoma and 19 controls,
      an experienced operator hand-corrected automatic segmentation of the combined RGC
      and inner plexiform layer (RGC+IPL) of 128 horizontal B-scans. To account for
      displacement of the RGC bodies around the fovea, the location of the SAP test
      points was adjusted to correspond to the location of the RGC bodies rather than
      to the photoreceptors, based on published histological findings. For analysis,
      RGC+IPL thickness vs SAP (TD) data were grouped into 5 eccentricities, from 3.4
      degrees  to 9.7 degrees  radius on the retina with respect to the fovea. RESULTS:
      The RGC+IPL thickness correlated well with SAP loss within approximately 7.2
      degrees  of the fovea (Spearman rho = 0.71-0.74). Agreement was worse (0.53-0.65)
      beyond 7.2 degrees , where the normal RGC layer is relatively thin. A linear
      model relating RGC+IPL thickness to linear SAP loss provided a reasonable fit for
      eccentricities within 7.2 degrees . CONCLUSION: In the central 7.2 degrees ,
      local RGC+IPL thickness correlated well with local sensitivity loss in glaucoma
      when the data were adjusted for RGC displacement.

PMID- 22159674
TI  - Neonatal bacteremia and retinopathy of prematurity: the ELGAN study.
AB  - OBJECTIVE: To explore whether early or late and presumed or definite neonatal
      bacteremia are associated with an increased risk of severe retinopathy of
      prematurity (ROP). METHODS: We evaluated 1059 infants born before week 28 of
      gestation for ROP. Infants were classified as having early (postnatal week 1) or
      late (weeks 2-4) definite (culture-proven) or presumed (antibiotics taken for >72
      hours despite negative blood culture results) bacteremia. Severe ROP was defined
      as stage 3 to 5, zone 1, prethreshold/threshold, or plus disease. We used time
      oriented risk models to adjust for confounders. RESULTS: In univariable, but not
      multivariable, analysis, newborns with presumed early bacteremia were at
      increased risk for plus disease (odds ratio [OR], 1.7; 95% CI, 1.1-2.7), and
      those with definite early bacteremia were at increased risk for stage 3 to 5
      disease (1.9; 1.1-3.2). Infants who had presumed or definite late bacteremia were
      at increased risk for all 4 indicators of severe ROP in univariable analysis. In
      multivariable analysis, newborns with presumed late bacteremia were at increased
      risk for prethreshold/threshold ROP (OR, 1.8; 95% CI, 1.02-3.2), and those with
      definite late bacteremia were at increased risk for prethreshold/threshold ROP
      (1.8; 1.1-2.9) and plus disease (1.8; 1.05-2.9). CONCLUSIONS: Definite late
      neonatal bacteremia seems to be an independent risk factor for
      prethreshold/threshold ROP and plus disease, and presumed late bacteremia seems
      to be related to prethreshold/threshold ROP.

PMID- 22159675
TI  - Insights into levator muscle dysfunction in a cohort of patients with molecularly
      confirmed blepharophimosis-ptosis-epicanthus inversus syndrome using high
      resolution imaging, anatomic examination, and histopathologic examination.
AB  - OBJECTIVE: To study the basis of defective levator palpebrae superioris (LPS)
      function in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), an
      autosomal dominant eyelid malformation sometimes associated with ovarian
      dysfunction. METHODS: Eight patients with molecularly proved BPES underwent high
      resolution surface-coil 3-T magnetic resonance imaging before surgical
      intervention. The features of LPS muscle and adjoining connective tissue were
      compared with an age-matched control subject. During LPS resection for ptosis
      repair, detailed anatomic examination of the LPS was performed. Histopathologic
      characteristics were compared with normal control samples from a cadaver and a
      patient with simple severe congenital ptosis. RESULTS: The most striking feature
      shown on magnetic resonance imaging was the thin, long anterior part of the LPS.
      During the operation, this consisted of a disorganized, thin, long aponeurosis.
      However, in the posterior part of the LPS, there was an organized thick structure
      suggestive of a muscle belly. Histopathologic examination revealed posteriorly
      well-formed striated muscle fibers in all patients with BPES but not in the
      control sample from the patient with simple severe congenital ptosis. These
      striated muscle fibers were comparable to those of the normal control tissue but
      were more intermixed with collagenous tissue and little fatty degeneration.
      CONCLUSIONS: The presence of striated muscle fibers in LPS of patients with BPES
      contrasts with the fatty degeneration in patients with simple severe congenital
      ptosis. To our knowledge, this is the first study providing novel insights into
      the pathogenesis of the eyelid malformation in BPES through extensive imaging,
      anatomic study, and histopathologic testing in a unique cohort of patients with
      molecularly proved BPES.

PMID- 22159676
TI  - Ability of an upright-supine test to differentiate skew deviation from other
      vertical strabismus causes.
AB  - OBJECTIVE: To determine the sensitivity and specificity of a new upright-supine
      test to differentiate skew deviation from trochlear nerve palsy and other causes
      of vertical strabismus in a large number of patients. METHODS: The study
      consisted of 125 consecutive patients who sought treatment from January 1, 2008,
      through December 31, 2010, for vertical strabismus of various causes: skew
      deviation (25 patients), trochlear nerve palsy (58 patients), restrictive causes
      (14 patients), and other causes (eg, myasthenia gravis and childhood strabismus)
      (28 patients). Twenty healthy participants served as controls. The deviation was
      measured by the prism and alternate cover test using a near target at &frac13; m
      in both the upright and supine positions. A vertical strabismus that decreased by
      50% or more from the upright to supine position constituted a positive test
      result. RESULTS: The upright-supine test result was positive in 20 of 25 patients
      with skew deviation (sensitivity, 80%) but negative in all patients with
      trochlear nerve palsy, restrictive, or other causes (specificity, 100%).
      CONCLUSIONS: The upright-supine test is highly specific for differentiating skew
      deviation from other causes of vertical strabismus. This test could be added as a
      fourth step after the 3-step test, and if the result is positive, neuroimaging
      should be considered if indicated clinically.

PMID- 22159677
TI  - Characterization of computed tomography scan abnormalities in patients with
      biopsy-proven hepatic metastases from uveal melanoma.
AB  - OBJECTIVES: To describe the computed tomography (CT) features in patients with
      biopsy-proven hepatic metastases of uveal melanoma and correlate these findings
      with survival. METHODS: The medical records of patients with uveal melanoma
      evaluated at Memorial Sloan-Kettering Cancer Center from January 1998 to
      September 2009 were reviewed. Inclusion criteria were biopsy-proven liver
      metastasis and CT scan images available within 2 months of biopsy. Exclusion
      criteria were prior systemic or liver-directed therapy for uveal melanoma.
      Statistical analyses were carried out using the t test, chi(2) test, and Kaplan
      Meier log-rank analyses. RESULTS: Of 505 medical records reviewed, 76 were
      selected for study. Characteristic CT findings included multiple (68 patients
      [90%]), hypodense (100%), heterogeneous (100%), and enhancing (100%) hepatic
      lesions with a mean dominant lesion size of 46.8 cm(2). Eighteen patients (24%)
      exhibited hepatomegaly. Predominant lesion size larger than 100 cm(2),
      hepatomegaly, and ascites correlated with a lower survival rate (P = .008, P <
      .001, and P < .001, respectively). Radiographic evidence of extrahepatic
      metastases was present in 40 patients (53%). However, the presence of
      extrahepatic metastases did not affect survival. The results of at least 1 liver
      function test were abnormal in 46 of 67 patients (69%), and elevation of at least
      1 serum transaminase and elevation of alkaline phosphatase were associated with
      larger lesions (P = .009 and P = .004, respectively) and hepatomegaly (P < .001
      for both). CONCLUSIONS: Radiographic evidence of predominant lesion size larger
      than 100 cm(2), hepatomegaly, and ascites-but not radiographic evidence of
      extrahepatic metastases-correlate with a lower survival rate in patients with
      biopsy-proven hepatic metastases of uveal melanoma.

PMID- 22159678
TI  - Cellular inflammation in nonarteritic anterior ischemic optic neuropathy and its
      primate model.
AB  - OBJECTIVE: To correlate potential inflammatory responses in nonarteritic anterior
      ischemic optic neuropathy (NAION) with a lesion possessing many physiologic and
      histologic similarities from a model of nonhuman primate NAION (pNAION). METHODS:
      Using immunohistochemistry and confocal microscopic analysis, we evaluated the
      relative numbers of inflammatory cell types in the single available clinical
      specimen of early NAION (21 days after event). We correlated this with the
      temporal inflammatory response occurring in optic nerve tissue at different times
      following pNAION induction. RESULTS: In pNAION, there is a previously unsuspected
      infiltration of polymorphonuclear leukocytes occurring almost immediately after
      infarct induction, followed by invasion of ED1+ extrinsic macrophages, which
      peaks 5 weeks after infarct. Intrinsic microglia accumulate up to 70 days after
      induction in the area of primary axonal loss. The analyzed human NAION specimen
      was similar to 21-day pNAION tissue, with extrinsic macrophages and intrinsic
      microglial cells in the region of focal axon loss. CONCLUSIONS: Cellular
      inflammation plays a major early role following white-matter (optic nerve)
      infarct, with both polymorphonuclear leukocyte and macrophage function involved
      in debris elimination and tissue remodeling. The optic nerve in NAION and its
      primate model are associated with early cellular inflammation, previously
      unsuspected, that may contribute to postinfarct optic nerve damage.

PMID- 22159679
TI  - Tailored and targeted interventions to encourage dilated fundus examinations in
      older African Americans.
AB  - OBJECTIVES: To compare the effects of a tailored (individualized) and targeted
      (designed for a subgroup) print intervention in promoting dilated fundus
      examinations (DFEs) in older African Americans and to determine whether other
      factors (eg, demographics, preventive health practices, health literacy score,
      behavioral intentions, and DFE rates) are associated with getting a DFE. METHODS:
      African Americans aged 65 years or older who had not had a DFE in at least 2
      years were recruited from community settings. Participants were randomized to
      receive either a tailored or targeted newsletter. Telephone follow-up was
      conducted at 1, 3, and 6 months to ascertain eye examination status. All
      participant-reported DFEs were confirmed by contacting their eye doctor
      (optometrist or ophthalmologist) by telephone. Main Outcome Measure  Eye doctor
      confirmed DFE at 6 months. RESULTS: Of the 329 participants enrolled, 128 (38.9%)
      had an eye doctor-confirmed DFE. No significant difference was noted in this
      measure by intervention group (relative risk, 1.07; 95% confidence interval, 0.82
      1.40), with 66 participants in the tailored group (40.2%) and 62 participants in
      the targeted group (37.6%) having an eye doctor-confirmed DFE. Based on logistic
      regression analysis, reading the newsletter (odds ratio, 1.76; 95% confidence
      interval, 1.08-2.87) and planning to make an appointment for a DFE (odds ratio,
      2.46; 95% confidence interval, 1.42-4.26) were significant predictors for DFE.
      CONCLUSIONS: The tailored and targeted interventions were equally effective in
      promoting eye doctor-confirmed DFEs at 6 months. Given the increased cost and
      effort associated with tailoring, our results suggest that well-designed targeted
      print messages can motivate older African Americans to get DFEs. Trial
      Registration  clinicaltrials.gov Identifier: NCT00649766.

PMID- 22159680
TI  - Microincision vitrectomy procedure using Intrector technology.
AB  - OBJECTIVE: To describe the procedure of pars plana vitrectomy (PPV) using an
      instrument designed for microincision vitrectomy. METHODS: In this retrospective,
      noncomparative, interventional case series, 6 different surgeons performed 4509
      PPV procedures from August 1, 2005, through May 31, 2010, with 1-port vitrectomy
      using a miniaturized multifunction probe (the Intrector). RESULTS: Complications
      were reported in 20 eyes (0.44%). Culture-positive endophthalmitis occurred in 2
      eyes (0.04%), sterile endophthalmitis occurred in 6 eyes (0.13%), intraoperative
      or postoperative retinal detachment occurred in 4 eyes (0.09%), and vitreous
      hemorrhage occurred in 8 eyes (0.18%). None of the 20 eyes with complications of
      4509 total eyes had worse visual outcomes than preoperative visual acuity.
      CONCLUSION: One-port vitrectomy using the Intrector is a procedure that can be
      used efficiently for selected cases that do not require membrane peeling.

PMID- 22159681
TI  - Risk assessment models for late age-related macular degeneration.

PMID- 22159682
TI  - Endophthalmitis after intravitreal injections: should the use of face masks be
      the standard of care?

PMID- 22159683
TI  - Use of autologous serum in the treatment of ocular surface disorders.

PMID- 22159684
TI  - Fifty years of ophthalmic laser therapy.

PMID- 22159685
TI  - Insertion slanting strabismus surgical procedures.
AB  - Insertion slanting recessions or biased resections have been reported to be
      useful for treating A- and V-pattern strabismus, convergence insufficiency, and
      convergence excess esotropia. Paradoxically, good results have been reported with
      methods that are opposite in nature. For example, some researchers would recess
      the medial rectus muscles and slant the superior pole of each muscle back farther
      than the inferior pole (Simonsz/von Graefe method) for a V-pattern esotropia, and
      others would slant the inferior poles back farther (Bietti method). The
      Simonsz/von Graefe method seems to be based on sound concepts of oculomotor
      mechanics. The Bietti method has been justified based on a misquoting and
      misinterpretation of previous work by Alan Scott, MD. Probably neither method
      contributes substantially to the outcome of strabismus surgery because sarcomere
      remodeling should rapidly negate the effect of the slanting. Most likely it is
      the recession or resection itself that affects the outcome.

PMID- 22159687
TI  - Human herpesvirus 8 in corneal endotheliitis resulting in graft failure after
      penetrating keratoplasty refractory to allograft rejection therapy.

PMID- 22159686
TI  - Responsiveness of choroidal neovascular membranes in patients with R345W mutation
      in fibulin 3 (Doyne honeycomb retinal dystrophy) to anti-vascular endothelial
      growth factor therapy.

PMID- 22159688
TI  - The 10-year incidence of glaucoma among patients with treated and untreated
      ocular hypertension.

PMID- 22159689
TI  - Progressive synechial angle closure from an enlarging Soemmering ring.

PMID- 22159690
TI  - Photoreceptor restoration in unilateral acute idiopathic maculopathy on adaptive
      optics scanning laser ophthalmoscopy.

PMID- 22159691
TI  - Mesectodermal suprauveal iridociliary leiomyoma: transscleral excision without
      postoperative iris defect.

PMID- 22159692
TI  - A report of high intraocular pressure with the dexamethasone intravitreal
      implant.

PMID- 22159694
TI  - Prevalence and risk factors of HPV infection among women from various provinces
      of the world.
AB  - OBJECTIVE: We set to estimate the genotype-specific prevalence of human papilloma
      virus (HPV) and its associated risk factors responsible among women with normal
      and abnormal cytology by systematic literature survey. METHODS: Reports on HPV
      prevalence published between 2000 and 2011 were retrieved. To be included,
      studies required information on cervical cytology, plus detailed descriptions of
      study populations, methods used to collect cervical samples, and assays used for
      HPV DNA detection and typing. Final analyses included 280 studies of which 120
      were included in the final analysis. The OR, 95% CI and P value were calculated
      using SPSS 16.0. RESULTS: Overall HPV prevalence in 576,281 women was estimated
      to be 32.1% (95% CI 32.098, 32.102). Corresponding estimates by region showed
      Eastern Asia (China) with the highest prevalence of about 57.7% of the HPV
      infection followed by South Central Asia (Indian subcontinent). The HPV
      prevalence was higher in less developed countries (42.2%) than in more developed
      regions (22.6%). The type-specific HPV prevalence study showed HPV 16 (9.5%) and
      18 (6.2%) to be the prevalent type irrespective of the region of study. First
      coitus at a younger (<= 15) age, increased number of pregnancies, increased
      number of sexual partners, use of contraceptives, smoking and chewing habit and
      early age at marriage were recognized as the significant risk factors for HPV
      infection. The phylogenetic analysis of HPV-16 showed the clustering of Indian
      sequence with the European and American sequences suggesting a similarity between
      HPV types. Even though the oncogenic proteins of HPV-16 detected in more
      developed and less developed regions clustered, the prevalence and the severity
      of the diseases among the less developed regions could be well explained as the
      exposure of the population to the possible associated risk factors concerning to
      the living conditions and nature of the life style adopted by the population.

PMID- 22159695
TI  - A randomized controlled trial of anorectal biofeedback for constipation.
AB  - PURPOSE: The purposes of this study were: (1) to examine the efficacy of
      anorectal biofeedback (AB) for constipation compared to a biofeedback control
      (BC) treatment and (2) to examine the extent to which self-reported childhood
      sexual/physical abuse predicted biofeedback outcome. METHODS: Twenty-one patients
      with pelvic floor dyssynergia were randomized to either (1) an AB arm, where
      patients learned to isolate the anal sphincter using an electromyography probe,
      or (2) a BC arm that controlled for the nonspecific effects of biofeedback, where
      patients learned to relax trapezius or temporalis muscles with EMG feedback. Both
      treatments were delivered by registered nurses for six sessions. Prior to
      randomization and post-treatment, patients completed the validated Constipation
      Severity Instrument and two measures of quality of life (QOL), the Irritable
      Bowel Syndrome-QOL, and the SF-36. Generalized estimating equations examined the
      within-group and between-group differences over time. RESULTS: Pre- and post
      treatment data were obtained for six AB and nine BC patients. AB patients'
      overall constipation severity scores decreased by 35.5% (vs. 15.3%), and their
      obstructive defecation symptom scores decreased by 37.9% (vs. 19.7%) compared to
      BC. A similar pattern was shown on the IBS-QOL. On the SF-36 Mental Health
      Composite (MCS), AB scores improved 28.0% compared to BC scores, which worsened
      12.7%. Those without (vs. with) a childhood sexual/physical abuse history showed
      improvement on the MCS post-biofeedback. CONCLUSIONS: While our sample was
      statistically underpowered, AB produced clinical improvements in constipation
      severity and QOL.

PMID- 22159696
TI  - Colonic bowel wall thickening: is there a need for endoscopic evaluation?
AB  - PURPOSE: Clinical relevance of colonic bowel wall thickening seen on abdominal CT
      scans is unknown. Recommendations for further diagnostic procedures are lacking.
      The aim of this retrospective study was to evaluate detecting of bowel wall
      thickening on CT scan and findings that were seen in case of endoscopical
      evaluation. METHODS: The radiological database was retrospectively reviewed for
      all reports of CT scans from 2003 to 2009 at the University Hospital Regensburg,
      Germany. Patients with underlying diseases for suspected bowel wall thickening
      were excluded. RESULTS: Sixty-two patients with bowel wall thickening were
      detected. Twenty-one percent (13/62) had generalized bowel wall thickening. In
      58%, bowel wall thickening was limited to one segment of the colon (36/62),
      mostly left sided (25/62). Forty-four percent of patients (27/62) were sent to
      endoscopy. In 15% (4/27), malignancy was suspected, and it could be
      histologically confirmed in two patients. Nineteen percent (5/27) had normal
      endoscopy, and 67% (18/62) showed benign findings. CONCLUSION: Colonic bowel wall
      thickening is not a common finding on CT scan in this study. Consequential
      endoscopic evaluation was performed in less than 50% of patients. Pathological
      findings were detected in 80% of these patients. We recommend endoscopical
      evaluation if bowel wall thickening is reported on CT scan.

PMID- 22159697
TI  - Diagnostic accuracy of C-reactive protein and white blood cell counts in the
      early detection of infectious complications after colorectal surgery.

PMID- 22159698
TI  - Inhibition of heme oxygenase-1 partially reverses the arsenite-mediated decrease
      of CYP1A1, CYP1A2, CYP3A23, and CYP3A2 catalytic activity in isolated rat
      hepatocytes.
AB  - Heme oxygenase (HO-1), the rate-limiting enzyme in the physiological breakdown of
      heme, is ubiquitous, and its expression can be increased by arsenite [As(III)],
      and similar other stimuli that induce cellular oxidative stress. Interestingly,
      it has been shown that the As(III)-induced HO-1 is inversely correlated with a
      decrease in cytochromes P450 (P450s) activity; however, the direct role for HO-1
      in the inhibition of P450 enzymes remains unknown. Our results showed that
      As(III) at a concentration of 5 MUM decreased the constitutive and inducible
      expression of CYP1A1, CYP1A2, CYP3A23, and CYP3A2 at the mRNA, protein, and
      catalytic activity levels. Moreover, As(III) decreased the nuclear accumulation
      of aryl hydrocarbon receptor (AhR) and pregnane X receptor without increasing
      their degradation. As(III) also increased the binding of cytosolic AhR to heat
      shock protein 90 and hepatitis B virus X-associated protein 2. In the presence of
      2,3,7,8-tetrachlorodibenzo-p-dioxin as an inducer for CYP1A and rifampin as an
      inducer for CYP3A, As(III) decreased the enzymatic activity of the four P450s
      more than it decreased their mRNA or protein expression levels. It is noteworthy
      that treatment with the competitive HO-1 inhibitor, tin-mesoporphyrin, or
      supplementing external heme partially reversed the As(III)-mediated decrease in
      activities of the four P450s. In conclusion, the current study provides the first
      evidence that As(III) decreases CYP1A1, CYP1A2, CYP3A23, and CYP3A2 expression in
      freshly isolated rat primary hepatocytes. Furthermore, inhibiting the As(III)
      mediated induction of HO-1 partially restores the enzymatic activity of these
      P450s that was initially decreased by As(III), confirming the direct role of HO-1
      in the inhibition of P450s.

PMID- 22159699
TI  - Which CYP2B6 variants have functional consequences for cyclophosphamide
      bioactivation?

PMID- 22159700
TI  - [Medicine and economy are not a contradiction].

PMID- 22159701
TI  - [Market and competitive positioning of specialized practices: competitive
      advantages through strategic productivity planning].
AB  - The provision of outpatient services will be confronted by increased market
      concentration. Under these circumstances, individual medical practices are
      predicted to have a minimal chance for survival since by nature the specialized
      physician can only accommodate the considerably heterogeneous needs of the
      patients up to justifiable limits. Due to patients' higher rate of mobility in
      the elective process, specialty physicians in rural areas are obliged to
      transform their practices into professional service enterprises. While hospitals
      are attempting to combat a continuing economization of the health care sector, in
      part by applying aggressive leadership and management methods, an increasing
      polarization can be noted in the outpatient setting. Also in the field of
      urology, patients consider themselves medical treatment clients who are unwilling
      to be relegated to cases of the often criticized"5-minute medicine."

PMID- 22159702
TI  - [Pharmacoeconomics in uro-oncology: the concept of QALYs].
AB  - The QALY (quality-adjusted life year) is often used in pharmacoeconomic
      evaluations. It combines the two dimensions 'quality of life' and 'life
      expectancy' into one index. Quality of life is expressed as a utility,
      corresponding to a value between 0 (death) and 1 (perfect health). Life
      expectancy is then multiplied by the utility corresponding to the quality of life
      of the respective life time. Accordingly, 1 QALY corresponds to 1 year in perfect
      health (1 year multiplied by utility 1) or 2 years with a quality of life reduced
      by 50% (2 years multiplied by utility 0.5). Results of pharmacoeconomic
      evaluations are often reported as additional costs in relation to the added value
      of a new treatment, expressed as cost per additional QALY gained for the patient
      with the new therapeutic intervention. The main advantage of the QALY concept is
      its validity for all patients and indications. And the use of benefit measures
      which are not restricted to a specific indication is most important for resource
      allocation, i.e. to avoid that varying amounts of money are paid for the same
      health benefit in different disease areas.

PMID- 22159703
TI  - [Empathic leadership: shaping positive change].
AB  - This paper explains the concept of empathic leadership in the setting of
      fundamental organisational changes. It deals with the question of how you can
      establish a culture of leadership, which motivates employees positively and
      enthuses them for the upcoming changes. It discusses the basics of empathic
      leadership and considers the question of how handling of emotions influences
      change processes and how different management styles can be used supportively
      during changes. With the help of a practical example the different phases of
      change are presented from a management point of view. Thereby the theory of
      different levels of employee motivation is explained inter alia. The article
      shows that empathic leadership also has a lasting economic effect. This can be
      seen particularly in the power of motivation for change, in addition to
      recruitment and long-term employee retention.

PMID- 22159704
TI  - [Evaluation of cancer therapy from the perspective of a statutory health
      insurance].
AB  - Increasing life expectancy, the introduction of costly new drugs and
      contributions from the health fund which do not cover overall costs, all
      contribute to financial problems for statutory health insurances (SHI) in
      oncology. Only an evidence-based approach can help to address these problems. In
      a first step patient-relevant benefits have to be substantiated as a necessary
      prerequisite for coverage of any treatment by SHIs. For products with no
      additional benefit compared to established forms of therapy the price will be
      limited by the established cost-benefit ratio. For products with additional
      benefits pricing is more difficult. For this situation the Institute for Quality
      and Efficiency in Healthcare (IQWiG) has developed general methods for the
      assessment of the relation of benefits to costs. Pricing based on this health
      economic evaluation is developed using efficiency frontier plots. However, this
      method is prone to manipulation and needs to be refined. Therapies without
      comparators, so-called soloists, cannot be priced in this way. New approaches to
      increase cost efficiency need to be developed in order to ensure the availability
      of high quality care in the future.

PMID- 22159705
TI  - [First line therapy for local advanced or metastasized urothelial carcinoma:
      randomized double-blind phase II study to compare gemcitabin and cisplatin in
      combination with OGX-427 or placebo for advanced transitional cell carcinoma of
      the bladder (OGX-427 - AB 39/11 of the Working Group Urological Oncology)].

PMID- 22159710
TI  - RANK(L)-ing biomarkers as surrogates for coronary calcium score.

PMID- 22159711
TI  - Weighted integration of visual position information.
AB  - The ability to localize visual objects is a fundamental component of human
      behavior and requires the integration of position information from object
      components. The retinal eccentricity of a stimulus and the locus of spatial
      attention can affect object localization, but it is unclear whether these factors
      alter the global localization of the object, the localization of object
      components, or both. We used psychophysical methods in humans to quantify
      behavioral responses in a centroid estimation task. Subjects located the centroid
      of briefly presented random dot patterns (RDPs). A peripheral cue was used to
      bias attention toward one side of the display. We found that although subjects
      were able to localize centroid positions reliably, they typically had a bias
      toward the fovea and a shift toward the locus of attention. We compared
      quantitative models that explain these effects either as biased global
      localization of the RDPs or as anisotropic integration of weighted dot component
      positions. A model that allowed retinal eccentricity and spatial attention to
      alter the weights assigned to individual dot positions best explained subjects'
      performance. These results show that global position perception depends on both
      the retinal eccentricity of stimulus components and their positions relative to
      the current locus of attention.

PMID- 22159712
TI  - The apoptosis regulators p53, bax and PUMA: Relationship and impact on outcome in
      early stage (FIGO I-II) ovarian carcinoma after post-surgical taxane-based
      treatment.
AB  - The objective of this study was to evaluate the prognostic effect of the
      apoptosis regulators p53, bax and PUMA for recurrent disease and disease-free
      survival (DFS) in a series of 105 patients in FIGO-stages I-II with epithelial
      ovarian cancer, all treated with post-surgical platinum-taxane chemotherapy. For
      the detection of positivity of the biological markers p53, bax and PUMA the
      techniques of tissue microarrays and immunohistochemistry (IHC) were used. In
      tumors the frequency of p53 positivity was 24%, that of bax positivity was 83%,
      and strong positivity was found for PUMA (43%). The bax status was related to
      tumor grade (P=0.029). Positive staining for bax was related to strong positivity
      of PUMA in the tumors (P=0.004). The p53, bax or PUMA status alone or concomitant
      (p53 bax, p53 PUMA and bax PUMA) were not related to age, histopathological
      subtype, serous/non-serous tumors or type of the staging procedure at primary
      surgery. In survival analysis p53-positive tumors (P=0.014) and concomitant p53
      positive and weak PUMA-positive tumors (P=0.015) were significantly correlated
      with shorter DFS. Concomitant p53-negative and bax-positive tumors were
      significantly correlated with longer survival (P=0.019). FIGO-stage (OR=6.0) and
      p53 status (OR=4.1) were predictive factors for tumor recurrence in logistic
      regression analysis and independent prognostic factors (HR=2.4 for both) in
      multivariate Cox regression analysis. In a separate Cox multivariate regression
      analysis the p53 bax status (HR=2.2) was an independent prognostic factor for
      DFS. The p53 PUMA status (HR=0.4) was not an independent prognostic factor,
      however, a borderline significance (P=0.07) was noted. Our results indicate that
      FIGO stage and p53 status alone were independent predictive factors for
      recurrence and prognostic factors for survival. Furthermore, p53 bax status was
      an independent prognostic factor for survival in this study.

PMID- 22159713
TI  - Recent trends in the management of maculopathy secondary to pathological myopia.
AB  - BACKGROUND: Pathological myopia is a frequent cause of secondary visual
      disturbance in young individuals worldwide. Myopic maculopathy describes a
      spectrum of clinical changes that comprise the main cause of visual loss among
      highly myopic individuals. Our aim is to describe current trends in the medical
      and surgical management of maculopathy secondary to pathological myopia. METHODS:
      The epidemiology, natural history, medical and surgical treatment modalities for
      choroidal neovascular membrane (CNV) and vitreomacular disorders secondary to
      pathological myopia (PM) are reviewed and evaluated. RESULTS: The medical and
      surgical treatment modalities in the management of myopic maculopathy have
      evolved over time. Laser photocoagulation, photodynamic therapy with verteporfin
      and other medical treatments have been superseded by the use of anti-vascular
      endothelial growth factor in the management of CNV secondary to PM. Surgical
      treatments are beneficial in the treatment of vitreomacular interface disorders
      such as macular hole retinal detachment and macular traction; however, primary
      success rates remain lower than those for non-myopic individuals. CONCLUSIONS:
      This updated clinical perspective demonstrates that CNV and vitreomacular
      disorders in pathological myopia are treatable conditions. There are numerous
      medical and surgical interventions that have significantly improved the outcome
      of myopic maculopathy and several others currently under investigation.
      Nonetheless, as technology advances, further well-designed studies are necessary
      to establish a uniform evidence-based approach for classification and treatment.

PMID- 22159714
TI  - The CD49d+/high subpopulation from isolated human breast sarcoma spheres
      possesses tumor-initiating ability.
AB  - Primary breast sarcomas (PBSs) that arise from mammary stroma are very rare,
      highly aggressive and therapy- resistant tumors with a heterogeneous phenotype.
      In this study, we sought to identify tumor-initiating cells (TICs) in PBSs and to
      describe their features. We isolated long-term self-renewing sarcospheres
      (designated NDY-1) from primary breast carcinosarcoma tissue (sarcoma component
      >95%) using the anchorage-independent culture method. NDY-1 spheres expressed
      various mesenchymal cell markers, and their tumorigenic potential was markedly
      reduced in adherent culture conditions, compared to spheres. Screening for
      integrins revealed a marked decrease in CD49d expression in adherent culture
      conditions of NDY-1. The CD49d+/high subpopulation sorted from NDY-1 spheres
      displayed higher cell viability and sphere-forming ability than CD49d-/low
      population in vitro. Moreover, the CD49d+/high population displayed high tumor
      initiating ability in limiting dilution transplantation to NOD/SCID mice, and the
      xenotransplanted CD49d+/high population recapitulated the complexity of the
      original primary tumors. Greater doxorubicin resistance was exhibited by the
      CD49d+/high population, compared with the CD49d-/low population. Thus, our
      results collectively demonstrate that CD49d+/high cells from sarcospheres display
      enhanced sphere-forming, drug resistance and tumor-initiating abilities. To our
      knowledge, this is the first study to identify TICs from breast sarcoma.

PMID- 22159715
TI  - Hydrous RuO(2)-Carbon Nanofiber electrodes with high mass and electrode-specific
      capacitance for efficient energy storage.
AB  - We demonstrate a new strategy for the fabrication of supercapacitor electrodes
      possessing high mass and area-specific capacitance for efficient charge storage,
      which can be extremely useful for the development of light, compact and high
      performance supercapacitors for a variety of high power demanding applications.
      High mass and electrode area specific capacitances were attained by using Hydrous
      Ruthenium Oxide (HRO)-Carbon Nanofiber (CNF) hybrid electrodes prepared by the
      deposition of HRO (~31% Ru content) on both the outer and inner surfaces of a
      cylindrical hollow CNF having open tips. Electrochemical studies of the uniformly
      deposited HRO nanoparticles on the CNF surface showed a mass specific capacitance
      of 645 F g(-1) and an electrode specific capacitance of 1.29 F cm(-2) with a HRO
      CNF material loading of 2 mg cm(-2) in the supercapacitor electrodes. The mass
      specific capacitance of pure HRO is 301 F g(-1), whereas the mass specific
      capacitance of HRO in the HRO-CNF electrode is ~1300 F g(-1), which is very close
      to the theoretical capacitance of HRO. This enhanced charge storage ability, high
      rate capability, better cyclic stability and low ESR of the HRO-CNF will be
      useful for the development of high performance supercapacitors.

PMID- 22159717
TI  - The matrisome: in silico definition and in vivo characterization by proteomics of
      normal and tumor extracellular matrices.
AB  - The extracellular matrix (ECM) is a complex meshwork of cross-linked proteins
      providing both biophysical and biochemical cues that are important regulators of
      cell proliferation, survival, differentiation, and migration. We present here a
      proteomic strategy developed to characterize the in vivo ECM composition of
      normal tissues and tumors using enrichment of protein extracts for ECM components
      and subsequent analysis by mass spectrometry. In parallel, we have developed a
      bioinformatic approach to predict the in silico "matrisome" defined as the
      ensemble of ECM proteins and associated factors. We report the characterization
      of the extracellular matrices of murine lung and colon, each comprising more than
      100 ECM proteins and each presenting a characteristic signature. Moreover, using
      human tumor xenografts in mice, we show that both tumor cells and stromal cells
      contribute to the production of the tumor matrix and that tumors of differing
      metastatic potential differ in both the tumor- and the stroma-derived ECM
      components. The strategy we describe and illustrate here can be broadly applied
      and, to facilitate application of these methods by others, we provide resources
      including laboratory protocols, inventories of ECM domains and proteins, and
      instructions for bioinformatically deriving the human and mouse matrisome.

PMID- 22159719
TI  - International public health: between old and new paradigms.

PMID- 22159718
TI  - Ultra high resolution linear ion trap Orbitrap mass spectrometer (Orbitrap Elite)
      facilitates top down LC MS/MS and versatile peptide fragmentation modes.
AB  - Although only a few years old, the combination of a linear ion trap with an
      Orbitrap analyzer has become one of the standard mass spectrometers to
      characterize proteins and proteomes. Here we describe a novel version of this
      instrument family, the Orbitrap Elite, which is improved in three main areas. The
      ion transfer optics has an ion path that blocks the line of sight to achieve more
      robust operation. The tandem MS acquisition speed of the dual cell linear ion
      trap now exceeds 12 Hz. Most importantly, the resolving power of the Orbitrap
      analyzer has been increased twofold for the same transient length by employing a
      compact, high-field Orbitrap analyzer that almost doubles the observed
      frequencies. An enhanced Fourier Transform algorithm-incorporating phase
      information-further doubles the resolving power to 240,000 at m/z 400 for a 768
      ms transient. For top-down experiments, we combine a survey scan with a selected
      ion monitoring scan of the charge state of the protein to be fragmented and with
      several HCD microscans. Despite the 120,000 resolving power for SIM and HCD
      scans, the total cycle time is within several seconds and therefore suitable for
      liquid chromatography tandem MS. For bottom-up proteomics, we combined survey
      scans at 240,000 resolving power with data-dependent collision-induced
      dissociation of the 20 most abundant precursors in a total cycle time of 2.5 s
      increasing protein identifications in complex mixtures by about 30%. The speed of
      the Orbitrap Elite furthermore allows scan modes in which complementary
      dissociation mechanisms are routinely obtained of all fragmented peptides.

PMID- 22159720
TI  - Remaking international health: refreshing perspectives from Latin America.

PMID- 22159721
TI  - The Pan American Health Organization and international health: a history of
      training, conceptualization, and collective development.
AB  - A constantly changing and increasingly complex global environment requires
      leaders with special competencies to respond effectively to this scenario. Within
      this context, the Pan American Health Organization (PAHO) goes beyond traditional
      leadership training models both in terms of its design as well as its conceptual
      approach to international health. As an intergovernmental, centenary organization
      in health, PAHO allows participants a unique vantage point from which to
      conceptualize, share experiences and develop projects relevant to international
      health. Derived from over two decades of experience (1985-2006) training
      professionals through its predessor Training Program in International Health, the
      Leaders in International Health Program "Edmundo Granda Ugalde" (LIHP) utilizes
      an innovative design, virtual and practical learning activities, and a problem
      based approach to analyze the main concepts, theories, actors, forces, and
      processes relevant to international health. In collaboration with PAHO/WHO
      Representative Offices and national institutions, participants develop country
      projects based on priority health issues, many of which are integrated into the
      Organization's technical cooperation and/or implemented by relevant ministries
      and other entities in their respective countries/subregions. A total of 185
      participants representing 31 countries have participated in the LIHP since its
      inception in 2008, building upon the 187 trained through its predecessor. These
      initiatives have contributed to the development of health professionals in the
      Region of the Americas devoted to international health, as well as provided
      important input towards a conceptual understanding of international health by
      fostering debate on this issue.

PMID- 22159722
TI  - [International financing for cooperation to develop health in Latin America and
      the Caribbean].
AB  - The purpose of this study is (a) to examine the ways in which Latin America and
      the Caribbean (LAC) have benefited from increases in international development
      assistance for health (DAH) at the global level and whether the trend observed
      after the Millennium Summit has also applied to the Region; (b) to determine
      whether there are differences in the distribution of this assistance, based on
      the gross per capita income of each country; (c) to identify the possible effects
      of the 2008 international financial crisis on official bilateral assistance; and
      (d) to compare trends in public health expenditure in relation to DAH before and
      after the Millennium Summit. The study has found that DAH in LAC follows a very
      different pattern than in other regions of the world. The period from 1997 to
      2008 was one of fluctuating stagnation, with average annual disbursements of US$
      1 200 million. Multilateral financial institutions accounted for 79% of the
      average disbursements in the upper-middle income countries between 2002 and 2008,
      while official bilateral assistance held the greatest share (61%) in the low- and
      lower-middle income countries. Bilateral assistance grew at an annual rate of 13%
      during this period, but in the year after the crisis, disbursements fell to US$
      20 million. Sixty-four percent of bilateral assistance came from the United
      States, Spain, and Canada, with 29% of it being directed to HIV/AIDS and sexually
      transmitted diseases. After the Millennium Summit DAH channeled to governments
      decreased 30% in the period 2001-2006, and its share of public health expenditure
      in the region was 0.3% for the same period, with an equally marginal proportion
      in relation to total health expenditure for 2008 (0.37%; US$ 2 per capita). The
      study concludes that after the Millennium Summit, DAH in LAC did not grow nor did
      it equal the trends prior to 2000, and public health expenditure followed its
      historical growth trend, without further increases in relation to the regional
      gross domestic product. Given these realities and the fact that LAC is the
      world's most unequal region, but not its poorest, it is imperative to reconsider
      the concepts, management, and delivery of cooperation in the development of
      health, using innovative approaches and alternative financing mechanisms that
      respond more effectively to the realities of the region.

PMID- 22159723
TI  - [International health and new forms of association: the Multipartite Dialogue and
      the Partners Forum].
AB  - Two cooperative public health initiatives involving representatives of civil
      society, academia, and the public and private sectors of the Americas are
      described and analyzed. One of them-the Multipartite Dialogue-promotes an
      intersectoral approach in its broadest sense, and the other-the Partners Forum
      while it represents an institutional initiative, pays particular attention to
      chronic noncommunicable diseases. Both are a call to action for governments and
      offer alternatives to tackle regional health problems more effectively.

PMID- 22159724
TI  - [An international health proposal to harmonize crossborder health surveillance].
AB  - A quantitative and qualitative study to identify mechanisms and actions to help
      harmonize cross-border health surveillance and provide a timely and effective
      response to events that may threaten international health security. The
      capacities of Brazil, Colombia, and Peru were analyzed in three areas: (a) the
      legal and administrative framework; (b) the ability to detect, evaluate, and
      report risk situations and (c) the ability to investigate, intervene in, and
      communicate international health risk situations. Data were collected through a
      document review, workshops, group work, and semistructured interviews with key
      individuals in health surveillance in the three countries. The average national
      capacity for the trio of countries within "the legal and administrative
      framework" was 69.4%; 83.3% in "the ability to detect, evaluate and report"; and
      78.7% in "the ability to investigate, intervene in, and communicate international
      health risk situations." More resources should be directed toward coordinated
      action among the three countries in order to strengthen surveillance and public
      health monitoring in their border areas.

PMID- 22159725
TI  - [Technical cooperation for health between Colombia and bordering countries].
AB  - OBJECTIVE: Characterize the technical cooperation of Colombia with four bordering
      countries and determine the training needs of the binational technical groups
      (BTGs). METHODS: Qualitative investigation based on document review and
      information provided by key actors in this field. To explore training needs, a
      survey of Colombia-Ecuador BTGs was conducted. Further information was obtained
      through discussion groups. Deductive and inductive categorization techniques were
      applied, as well as convergence using the triangulation method. RESULTS: Eighteen
      agreements/conventions and the documentation from 12 borderarea health
      cooperation projects were obtained. The majority of the projects involved
      multilateral cooperation. The two priority cooperation topics were the
      International Health Regulations and Millennium Development Goals 6 and 7. The
      BTGs considered training in management, health diplomacy, and capacity-building
      necessary for cooperation in border areas. CONCLUSIONS: The border areas
      exhibited complex intervention scenarios, where international law and foreign
      policy have defined cooperative actions. In determining the training for BTGs,
      the national and international regulatory framework and context of the border
      areas should be taken into account.

PMID- 22159726
TI  - [The 2010 earthquake in Chile: the response of the health system and
      international cooperation].
AB  - OBJECTIVE: Understand the health system and international cooperation response to
      the catastrophic situation left by the earthquake and tsunami of 27 February 2010
      in Chile, and draft proposals for improving strategies to mitigate the
      devastating effects of natural disasters. METHODS: Descriptive and qualitative
      study with a first phase involving the analysis of secondary information-such as
      news articles, official statements, and technical reports-and a second phase
      involving semistructured interviews of institutional actors in the public health
      sector responsible for disaster response and users of the health system who acted
      as leaders and/or managers of the response. The study was conducted between May
      and October 2010, and information-gathering focused on the Maule, Bio Bio, and
      Metropolitan regions. RESULTS: Procedures for recording, distributing, and
      controlling donations were lacking. The health services suffered significant
      damage, including the complete destruction of 10 hospitals. The presence of field
      hospitals and foreign medical teams were appreciated by the community. The family
      health model and the commitment of personnel helped to ensure the quality of the
      response. While public health management was generally good, problems dealing
      with mental health issues were encountered due to a lack of local plans and
      predisaster simulations. The poor were the most affected. Women became social
      leaders, organizing the community. CONCLUSIONS: Although the health response to
      the emergency was satisfactory, both the health system and the mobilization of
      international assistance suffered from weaknesses that exacerbated existing
      inequities, revealing the need for multisectoral participatory mitigation plans
      for better disaster preparedness.

PMID- 22159727
TI  - [Costly drugs: analysis and proposals for the Mercosur countries].
AB  - OBJECTIVE: Determine how the Mercosur countries access, regulate, and finance
      costly drugs and propose joint selection and financing strategies at the
      subregional level. METHODS: Qualitative design, using content analyses of primary
      and secondary sources, document reviews, interviews, focus groups, and case
      studies. The variables selected included: selection criteria, access, financing,
      and regulations in the various countries. Costly drugs were divided into those
      that do not alter the natural course of the disease and those with demonstrated
      efficacy, using the defined daily dose to compare the costs of classical
      treatments and those involving costly drugs. RESULTS: The Mercosur countries
      generally lack formal strategies for dealing with the demand for costly drugs,
      and governments and insurers wind up financing them by court order. The case
      studies show that there are costly drugs whose efficacy has not been established
      but that nonetheless generate demand. The fragmentation of procurement,
      international commitments with regard to intellectual property, and low
      negotiating power exponentially increase the price of costly drugs, putting
      health system finances in jeopardy. CONCLUSIONS: Costly drugs must be regulated
      and rationally selected so that only those that substantively benefit people are
      accepted. To finance the drugs so selected, common country strategies are needed
      that include such options as flexible in trade agreements, the creation of
      national resource funds, or joint procurement by countries to enhance their
      negotiating power.

PMID- 22159728
TI  - [The emigration of physicians in Venezuela].
AB  - OBJECTIVE: Ascertain the factors that could affect the intention of Venezuelan
      health professionals to emigrate to other countries. METHODS: Exploratory study
      that applied a semistructured interview and survey, respectively, to a population
      consisting of four health professionals and 36 medical students. The interview
      data were analyzed by deductive and inductive categorization and the survey data
      by means of univariate and bivariate analysis. RESULTS: It was observed that
      13.8% of the students generally intended to emigrate, with differences between
      the two study groups. It was found that work-related issues had a high motivating
      effect (16.6%), particularly the possibility of balancing work with personal
      life, better pay, access to continuing education, working in a better health
      system, and having the basic resources necessary for professional practice. It
      was determined that professional reasons had a moderate motivating effect
      (13.8%), whereas personal and contextual reasons had little influence (less than
      3%). Although the interviews of physicians who had obtained their medical degree
      revealed clashes involving political and economic interests, only 5.5% of the
      students surveyed considered the political or economic situation a determinant in
      the emigration of professionals. CONCLUSIONS: It is recommended that the
      management and professional development of medical personnel be strengthened,
      reconciling their expectations with the legal framework and needs of the health
      system. A formal system for tracking the emigration of professionals and
      broadening the study of the causative factors at the national level should be set
      up, since better knowledge about the phenomena linked with emigration would help
      generate and support proposals to guarantee self-sufficiency with respect to
      human resources for health.

PMID- 22159729
TI  - [Mercosur's regional health agenda: architecture and themes].
AB  - This article describes the shaping of institutional health spaces in the
      Mercosur, with analysis of themes and results and considerations on the
      construction of the regional agenda and on the effects of regional economic
      integration processes on health policies and systems. We discuss the
      organization, operation, focus topics, and results achieved in specific health
      forums (Meeting of Ministers of Health and Sub-Working Group 11), seeking to
      analyze the architecture and issues addressed by the regional agenda and drawing
      parallels with the European experience. The aim of this reflection is to identify
      how the work done by Mercosur structures contributes to building a regional
      agenda, with the expectation that the integration can contribute to reducing
      inequalities in access to health care in the region.

PMID- 22159730
TI  - Modeling the spread of Phytophthora.
AB  - We consider a model for the morphology and growth of the fungus-like plant
      pathogen Phytophthora using the example of Phytophthora plurivora. Here, we are
      utilizing a correlated random walk describing the density of tips. This random
      walk incorporates a delay in branching behavior: newly split tips only start to
      grow after a short while. First, we question the effect of such a delay on the
      running fronts, for uniform- as well as non-uniform turning kernels. We find that
      this delay primarily influences the slope of the front and therewith the way of
      spatial appropriation, and not its velocity. Our theoretical predictions are
      confirmed by the growth of Phytophthora in concrete experiments performed in
      Petri dishes. The second question addressed in this paper, concerns the manner
      tips are interacting, especially the point why tips stop to grow "behind" the
      interface of the front, respectively in confrontation experiments at the
      interface between two colonies. The combination of experimental data about the
      spatially structured time course of the glucose concentration and simulations of
      a model taking into account both, tips and glucose, reveals that nutrient
      depletion is most likely the central mechanism of tip interaction and hyphal
      growth inhibition. We presume that this is the growing mechanism for our kind of
      Phytophthora in infected plant tissue. Thus, the pathogen will sap its hosts via
      energy depletion and tissue destruction in infected areas.

PMID- 22159731
TI  - Quantitative T2* magnetic resonance imaging for evaluation of iron deposition in
      the brain of beta-thalassemia patients.
AB  - BACKGROUND: Iron overload is a common clinical problem in patients with beta
      thalassemia major. The purpose of this study was to assess the presence of excess
      iron in certain areas of the brain (thalamus, midbrain, adenohypophysis and basal
      ganglia) in patients with beta-thalassemia major and evaluate the association
      with serum ferritin and liver iron content. MATERIALS AND METHODS: A cross
      sectional study on 53 patients with beta-thalassemia major and 40 healthy
      controls was carried out. All patients and healthy controls underwent magnetic
      resonance imaging (MRI) examinations of the brain and liver. Multiecho fast
      gradient echo sequence was used and T2* values were calculated based on the
      Brompton protocol. Correlations between T2* values in the brain with T2* values
      in the liver as well as serum ferritin levels were investigated. RESULTS: There
      were no significant differences between patients and healthy controls with
      respect to age and sex. Patients had significantly lower T2* values in basal
      ganglia (striatum), thalamus and adenohypophysis compared to controls while there
      were no differences in the midbrain (red nucleus). There were no significant
      correlations between liver T2* values or serum ferritin with T2* values of basal
      ganglia (striatum), thalamus and adenohypophysis in patients or healthy controls.
      There were no significant correlations between T2* values of adenohypophysis and
      thalamus or basal ganglia (striatum) while these variables were significantly
      correlated in healthy controls. CONCLUSIONS: Serum ferritin and liver iron
      content may not be good indicators of brain iron deposition in patients with beta
      thalassemia major. Nevertheless, the quantitative T2* MRI technique is useful for
      evaluation of brain iron overload in beta thalassemia major patients.

PMID- 22159732
TI  - How reliable is the attentional blink? Examining the relationships within and
      between attentional blink tasks over time.
AB  - When the second of two targets is presented temporally close (within 500 ms) to
      the first target in rapid serial visual presentation, accuracy for reporting the
      second target is markedly diminished-an attentional blink (AB). The AB has become
      a well-studied phenomenon, and multiple different versions of the AB are
      currently in use. However, little is known about the stability of individual
      performance on the AB. The current study examined the reliability of two
      different versions of the AB task (a task-switch and no-task-switch version)
      within session, and over the period of 7-10 days, in order to examine performance
      stability. In addition to testing the reliability, we also examined the
      relationship between both versions of our AB tasks. Both versions of the AB were
      shown to be reliable within session, and over time, suggesting that performance
      is quite stable on this task. In addition, performance on the two different AB
      tasks was significantly correlated within and across sessions, suggesting that
      the AB phenomenon is being accurately captured by versions of the AB that include
      a task-switch. These findings are important given the recent interest in
      individual differences in performance on the AB.

PMID- 22159733
TI  - Impact of an indigenous microbial enhanced oil recovery field trial on microbial
      community structure in a high pour-point oil reservoir.
AB  - Based on preliminary investigation of microbial populations in a high pour-point
      oil reservoir, an indigenous microbial enhanced oil recovery (MEOR) field trial
      was carried out. The purpose of the study is to reveal the impact of the
      indigenous MEOR process on microbial community structure in the oil reservoir
      using 16Sr DNA clone library technique. The detailed monitoring results showed
      significant response of microbial communities during the field trial and large
      discrepancies of stimulated microorganisms in the laboratory and in the natural
      oil reservoir. More specifically, after nutrients injection, the original
      dominant populations of Petrobacter and Alishewanella in the production wells
      almost disappeared. The expected desirable population of Pseudomonas aeruginosa,
      determined by enrichment experiments in laboratory, was stimulated successfully
      in two wells of the five monitored wells. Unexpectedly, another potential
      population of Pseudomonas pseudoalcaligenes which were not detected in the
      enrichment culture in laboratory was stimulated in the other three monitored
      production wells. In this study, monitoring of microbial community displayed a
      comprehensive alteration of microbial populations during the field trial to
      remedy the deficiency of culture-dependent monitoring methods. The results would
      help to develop and apply more MEOR processes.

PMID- 22159734
TI  - Effects of dissolved organic matter (DOM) at environmentally relevant carbon
      concentrations on atrazine degradation by Chelatobacter heintzii SalB.
AB  - The dissolved organic matter (DOM) is the term used for organic components of
      natural origin present in the soil solution and is probably the most available C
      source that primes microbial activity in subsoils. Contrasting effects of organic
      C components on pesticide degradation have been reported; however, most studies
      have used model organic compounds with compositions and concentrations which
      differ substantially from those found in the environment. Degradation of atrazine
      (AT) by Chelatobacter heintzii SalB was monitored in liquid batch assays in the
      absence or presence of well-defined model C compounds (glucose, gluconate and
      citrate) as model DOM (mDOM) or complex, less-defined, environmental DOM
      solutions (eDOM: isolated humic substances, soil and plant residue extracts) at
      environmentally relevant concentrations. Glucose significantly increased AT
      degradation rate by more than a factor of 8 at and above 2.5 mg C L( - 1).
      Optical density measurements showed that this stimulation is related to microbial
      growth. Gluconate and citrate had no effects unless at non-relevant
      concentrations (1,000 mg DOC L( - 1)) at which stimulations (gluconate) or
      inhibitions (citrate) were found. The effects of eDOM added at 10 mg DOC L( - 1)
      on AT degradation were generally small. The AT degradation time was reduced by
      factors 1.4-1.9 in the presence of humic acids and eDOM from soils amended with
      plant residues; however, no effects were found for fulvic acids or eDOM from a
      soil leachate solution or extracted from unamended peat or forest soil. In
      conclusion, DOM supplied as both mDOM and eDOM did not inhibit AT degradation at
      environmentally relevant concentrations, and stimulation can be found for
      selected DOM samples and this is partly related to its effect on growth.

PMID- 22159735
TI  - Biological synthesis of quercetin 3-O-N-acetylglucosamine conjugate using
      engineered Escherichia coli expressing UGT78D2.
AB  - Biotransformation of flavonoids using Escherichia coli harboring nucleotide sugar
      dependent uridine diphosphate-dependent glycosyltransferases (UGTs) commonly
      results in the production of a glucose conjugate because most UGTs are specific
      for UDP-glucose. The Arabidopsis enzyme AtUGT78D2 prefers UDP-glucose as a sugar
      donor and quercetin as a sugar acceptor. However, in vitro, AtUGT78D2 could use
      UDP-N-acetylglucosamine as a sugar donor, and whole cell biotransformation of
      quercetin using E. coli harboring AtUGT78D2 produced quercetin 3-O-N
      acetylglucosamine. In order to increase the production of quercetin 3-O-N
      acetylglucosamine via biotransformation, two E. coli mutant strains deleted in
      phosphoglucomutase (pgm) or glucose-1-phosphate uridylyltransferase (galU) were
      created. The galU mutant produced up to threefold more quercetin 3-O-N
      acetylglucosamine than wild type, resulting in the production of 380-mg/l
      quercetin 3-O-N-acetylglucosamine and a negligible amount of quercetin 3-O
      glucoside. These results show that construction of bacterial strains for the
      synthesis of unnatural flavonoid glycosides is possible through rational
      selection of the nucleotide sugar-dependent glycosyltransferase and engineering
      of the nucleotide sugar metabolic pathway in the host strain.

PMID- 22159736
TI  - Combinatorial modulation of galP and glk gene expression for improved alternative
      glucose utilization.
AB  - Phosphoenolpyruvate (PEP) is an important precursor for anaerobic production of
      succinate and malate. Although inactivating PEP/carbohydrate phosphotransferase
      systems (PTS) could increase PEP supply, the resulting strain had a low glucose
      utilization rate. In order to improve anaerobic glucose utilization rate for
      efficient production of succinate and malate, combinatorial modulation of
      galactose permease (galP) and glucokinase (glk) gene expression was carried out
      in chromosome of an Escherichia coli strain with inactivated PTS. Libraries of
      artificial regulatory parts, including promoter and messenger RNA stabilizing
      region (mRS), were firstly constructed in front of beta-galactosidase gene (lacZ)
      in E. coli chromosome through lambda-Red recombination. Most regulatory parts
      selected from mRS library had constitutive strengths under different cultivation
      conditions. A convenient one-step recombination method was then used to modulate
      galP and glk gene expression with different regulatory parts. Glucose utilization
      rates of strains modulated with either galP or glk all increased, and the rates
      had a positive relation with expression strength of both genes. Combinatorial
      modulation had a synergistic effect on glucose utilization rate. The highest rate
      (1.64 g/L h) was tenfold higher than PTS(-) strain and 39% higher than the wild
      type E. coli. These modulated strains could be used for efficient anaerobic
      production of succinate and malate.

PMID- 22159737
TI  - Polyclonal antibody against conserved sequences of mce1A protein blocks MTB
      infection in macrophages.
AB  - The pathogenesis of Mycobacterium tuberculosis is largely due to its ability to
      enter and survive within human macrophages. It is suggested that a specific
      protein namely mammalian cell entry protein is involved in the pathogenesis and
      the specific gene for this protein mce1A has been identified in several
      pathogenic organisms such as Rickettsia, Shigella, Escherichia coli,
      Helicobacter, Streptomyces, Klebsiella, Vibrio, Neisseria, Rhodococcus,
      Nocardioides, Saccharopolyspora erthyrae, and Pseudomonas. Analysis of mce1
      operons in the above mentioned organisms through bioinformatics tools has
      revealed the presence of unique sequences (conserved regions) suggesting that
      these sequences may be involved in the process of infection. Presently, the mce1A
      full-length (1,365 bp) region from Mycobacterium bovis and its conserved regions
      (303 bp) were cloned in to an expression vector and the purified expressed
      proteins of molecular weight ~47 and ~11 kDa, respectively, were injected to
      rabbits to raise the polyclonal antibodies. The purified polyclonal antibodies
      were checked for their ability to inhibit the Mycobacterium infection in cultured
      human macrophages. In macrophage invasion assay, when antibody added at high
      concentration, decrease in viable counts was observed in all cell cultures within
      the first 5 days after infection, where the intracellular bacterial CFU obtained
      from the infected MTB increased by the 3rd day at low concentration of antibody.
      The macrophage invasion assay has indicated that the purified antibodies of mce1A
      conserved region can inhibit the infection of Mycobacterium.

PMID- 22159738
TI  - Assessing the impact of alumina nanoparticles in an anaerobic consortium:
      methanogenic and humus reducing activity.
AB  - The impact of gamma-Al(2)O(3) nanoparticles (NP) on specific methanogenic
      activity (SMA) and humus reducing activity (HRA) in an anaerobic consortium was
      evaluated. SMA in sludge incubations without gamma-Al(2)O(3) was always higher
      compared with those performed in the presence of 100 g/L of gamma-Al(2)O(3).
      Nevertheless, the SMA in incubations with gamma-Al(2)O(3) was not completely
      inhibited, indicating that some methanogenic microorganisms were physiologically
      active even in the presence of gamma-Al(2)O(3) NP during the incubation period
      (~400 h). SMA and HRA of the anaerobic consortium were also conducted in the
      presence of gamma-Al(2)O(3) NP coated with humic acids (HA). Microbial HA
      reduction occurred 3.7-fold faster using HA immobilized on gamma-Al(2)O(3) NP
      (HA(Imm)), compared with the control with suspended HA (HA(Sus)). Furthermore,
      immobilized HA decreased the toxicological effects of gamma-Al(2)O(3) NP on
      methanogenesis. Scanning electron microscopy (SEM) images revealed cell membrane
      damage in those sludge incubations exposed to uncoated gamma-Al(2)O(3) NP. In
      contrast, cell damage was not observed in incubations with HA-coated gamma
      Al(2)O(3) NP. Methanogenesis out-competed microbial humus reduction regardless if
      HA was HA(Imm) or HA(Sus). The present study provides a clear demonstration that
      HA immobilized in gamma-Al(2)O(3) NP are effective terminal electron acceptor for
      microbial respiration and suggests that HA could mitigate the toxicological
      effects of metal oxide NP on anaerobic microorganisms.

PMID- 22159739
TI  - SMP production by activated sludge in the presence of a metabolic uncoupler,
      3,3',4',5-tetrachlorosalicylanilide (TCS).
AB  - 3,3',4',5-Tetrachlorosalicylanilide (TCS) is an effective metabolic uncoupler
      utilized for microbial yield reduction. However, its potential impact, in
      particular on the soluble microbial products (SMP) formation, is unknown yet.
      Herein we study the effect of TCS on SMP production and analyze the related
      mechanism. The addition of TCS in activated sludge system led to an increased
      production of SMP, especially proteins. The SMP were produced in proportion to
      the substrate utilization at a low TCS concentration, while more non-substrate
      associated SMP were released at a high TCS concentration. TCS simulated the
      production of extracellular polymeric substances (EPS) and enhanced cell lysis,
      which both contributed to SMP production. FTIR and EEM analyses show that the
      SMP, EPS, and cell lysis products have similar functional groups and fluorescence
      properties, indicating a similar origin of these substances. In addition, a dose
      of TCS increased the release of high molecular weight compounds due to cell
      lysis. This study might benefit for a better understanding of the response of
      activated sludge to metabolic uncouplers like TCS.

PMID- 22159740
TI  - Modulation of guanosine nucleotides biosynthetic pathways enhanced GDP-L-fucose
      production in recombinant Escherichia coli.
AB  - Guanosine 5'-triphosphate (GTP) is the key substrate for biosynthesis of
      guanosine 5'-diphosphate (GDP)-L-fucose. In this study, improvement of GDP-L
      fucose production was attempted by manipulating the biosynthetic pathway for
      guanosine nucleotides in recombinant Escherichia coli-producing GDP-L-fucose. The
      effects of overexpression of inosine 5'-monophosphate (IMP) dehydrogenase,
      guanosine 5'-monophosphate (GMP) synthetase (GuaB and GuaA), GMP reductase (GuaC)
      and guanosine-inosine kinase (Gsk) on GDP-L-fucose production were investigated
      in a series of fed-batch fermentations. Among the enzymes tested, overexpression
      of Gsk led to a significant improvement of GDP-L-fucose production. Maximum GDP-L
      fucose concentration of 305.5 +/- 5.3 mg l(-1) was obtained in the pH-stat fed
      batch fermentation of recombinant E. coli-overexpressing Gsk, which corresponds
      to a 58% enhancement in the GDP-L-fucose production compared with the control
      strain overexpressing GDP-L-fucose biosynthetic enzymes. Such an enhancement of
      GDP-L-fucose production could be due to the increase in the intracellular level
      of GMP.

PMID- 22159744
TI  - Evaluation of patients with Behcet's disease by cervical cytology and colposcopic
      examination.
AB  - PURPOSE: We evaluated the genital involvement in women with Behcet's disease (BD)
      by cervical cytology and colposcopy, and compared these findings with healthy
      controls. METHODS: A total of 152 women were referred to the Gynecology Clinic of
      Meram School of Medicine between March 2008 and December 2009. The study group
      was composed of 78 women with BD, and the control group included 74 healthy women
      admitted for routine gynecologic examination. These patients were subjected to
      cervical cytology and colposcopic examination. Cervical biopsy was performed in
      cases with abnormal cytology. These findings and some gynecologic complaints were
      compared. RESULTS: The demographic features were similar between each group.
      Genital involvement (scar + ulcer) was detected in 58 (74.3%) patients. The most
      common sites of ulcers (55.1%) and scars (7.6%) were the labia majora. Abnormal
      cytology in study and control groups was detected in nine (11.5%) and three (4%)
      of the patients, respectively, and a slight statistical significance was obtained
      (p = 0.048). Acetowhite and iodine-negative epithelium were higher in the study
      group than in controls (p = 0.015 and p = 0.042). Dyspareunia was higher in BD
      patients (p = 0.001). CONCLUSION: Patients with BD are more prone to having an
      abnormal cervical cytology and acetowhite and iodine-negative epithelium on
      colposcopic examination. However, these findings are mostly benign conditions.
      The complaint of dyspareunia should be considered during treatment of female
      patients with BD.

PMID- 22159745
TI  - The diagnostic value of the Doppler ultrasonography in distinguishing the
      endometrial malignancies in women with postmenopausal bleeding.
AB  - PURPOSE: To investigate the diagnostic value of blood flow measurements in
      endometrial, myometrial and uterine vasculature by transvaginal Doppler
      ultrasonography in the differentiation of the neoplastic endometrial pathologies
      in women with postmenopausal bleeding. METHODS: 106 women who presented with
      postmenopausal bleeding were enrolled in a prospective cohort study. Endometrial
      thickness, pulsatility and resistance indices of the uterine, myometrial and
      endometrial vasculature, endometrial histopathology were measured by transvaginal
      Doppler sonography. Dilatation and curettage were performed for all women.
      Sonographic and histopathological results were evaluated. RESULTS: Endometrial
      malignancy was diagnosed in 24 of the patients (22.7%). Endometrial thickness was
      found to be higher in the patients with malign histopathology compared with the
      patients of benign histopathology. Statistically, uterine artery PI, RI, radial
      artery PI, spiral artery PI, and RI were also significantly lower in patients
      with malign histopathology. According to ROC curve analysis the endometrial
      thickness of 5 mm, uterine artery PI of 1.450, uterine artery RI of 0.715, radial
      artery PI of 1.060, and radial artery RI of 0.645 were defined as the cut-off
      points. In multivariate regression model, only uterine artery PI was identified
      as independent determinant of malignant endometrium. CONCLUSIONS: Blood flow of
      uterine artery and also myometrial and endometrial vasculature displayed lower
      impedance in patients with malignant endometrium, but these lower indices are not
      already adequate for using as diagnostic tests.

PMID- 22159746
TI  - The management of stage III and IV endometriosis.
AB  - The clinical manifestations of severe endometriosis are variable and
      unpredictable in both presentation and course. There are also a proportion of
      women with severe endometriosis who remain asymptomatic. The treatment of severe
      endometriosis must be individualised, taking into account the impact of the
      disease and treatment on pain, fertility and quality of life. Surgery is usually
      required and multiple organs are sometimes involved. Therefore, if endometriosis
      is severe, referral to a center with the expertise to offer all available
      treatments in a multidisciplinary team, including advanced laparoscopic surgery
      and laparotomy, is strongly recommended. It is also important to involve the
      woman in all decisions, to be flexible in diagnostic and therapeutic thinking, to
      maintain a good relationship with the woman and to seek advice where appropriate.

PMID- 22159747
TI  - Screening for postpartum depression using Kurdish version of Edinburgh postnatal
      depression scale.
AB  - BACKGROUND: One of the important public health problems affecting maternal and
      child health is postpartum depression (PPD). It generally occurs within 6-8 weeks
      after childbirth. OBJECTIVES: To determine the prevalence of postpartum
      depression (PPD) using a Kurdish version of Edinburgh postpartum depression scale
      (EPDS) and to analyze the risk factors for postpartum depression in a population
      of puerperal Kurdish women in Erbil city. PATIENTS AND METHODS: A cross-sectional
      study was conducted between 20th of June and 30th of November 2010, in 14
      antenatal care units of primary health centers, in Erbil city, Kurdistan region,
      Iraq. The sample of the study included 1,000 puerperal women (6-8 weeks
      postpartum), ranging in age from 14 to 48 years. Data were collected after
      interviewing the women using a questionnaire designed by the researchers, and the
      Kurdish version of the EPDS. Chi square test of association and the logistic
      regression tests were used in the analysis. RESULTS: The prevalence of postpartum
      depression was 28.4%. Logistic regression analysis showed that the factors found
      to be associated with PPD were: physical or sexual abuse, delivery by cesarean
      section, history of past psychiatric illness, and family history of past
      psychiatric illness; while marriage with no previous agreement, and high socio
      economic level were associated with lower levels of PPD. CONCLUSION: The Kurdish
      version of the EPDS can be successfully used to screen depression in a Kurdish
      population of puerperal women.

PMID- 22159748
TI  - The impact of teriparatide adherence and persistence on fracture outcomes.
AB  - The study investigated the real-world relationship between teriparatide adherence
      and persistence and fracture outcomes in a US claims database. Fracture risk was
      estimated to decrease as adherence and persistence increased for any clinical,
      vertebral, and non-vertebral fractures. Greater emphasis on programs to increase
      patient adherence may improve clinical outcomes. INTRODUCTION: Adherence to
      osteoporosis treatment is essential for achieving optimal therapeutic outcomes.
      Previous findings from clinical trials and observational studies demonstrate that
      longer teriparatide (TPTD) exposure is associated with fewer fractures. The study
      aim was to investigate real-world relationships between TPTD adherence and
      persistence and fracture outcomes. METHODS: The Thomson Reuters MarketScan(r)
      database, 2004-2008, was used to identify TPTD users with continuous enrollment
      12 months pre- and 24 months post-TPTD initiation. Post-index fractures included
      vertebral and non-vertebral. Adherence (medication possession ratio, MPR) groups
      were defined as high (MPR >= 0.80), medium (0.5 <= MPR < 0.8), and low (MPR <
      0.5). Persistence groups were defined by periods 1-6, 7-12, 13-18, and 19-24
      months. Logistic regressions modeled fracture risk for any clinical, hip,
      vertebral, and non-vertebral fractures, controlling for patient characteristics,
      insurance and healthcare provider types, Charlson comorbidity index, bone mineral
      density screening, medication use, and fracture history. RESULTS: Among 3,587
      TPTD patients (mean age 68.9 years; 91% female), fracture risk was lowest in high
      MPR patients in all models except hip (OR = 1.17; p = 0.64). Medium versus high
      MPR was a significant risk factor for any fracture (OR = 1.49; p = 0.004) and non
      vertebral fracture (OR = 1.45; p = 0.014); low-MPR was a significant risk factor
      for any fracture (OR = 1.64; p < 0.01), vertebral fracture (OR = 2.56; p =
      0.001), and non-vertebral fracture (OR = 1.44; p = 0.013). Persistence of 1-6
      months versus 19-24 months was associated with higher risk for any clinical (OR =
      1.88, p < 0.001), vertebral (OR = 3.69; p < 0.001), and non-vertebral fracture
      (OR = 1.51; p = 0.011), but not hip (OR = 1.93; p = 0.08). CONCLUSIONS: Fracture
      risk decreased as TPTD adherence and persistence increased for any clinical,
      vertebral, and non-vertebral fractures.

PMID- 22159750
TI  - RETRACTED ARTICLE: Vertebroplasty: an international point of view on this
      "minimally invasive" surgical technique.

PMID- 22159749
TI  - Does maternal long chain polyunsaturated fatty acid status in pregnancy influence
      the bone health of children? The Southampton Women's Survey.
AB  - In this large, population-based, prospective, mother-offspring cohort study,
      maternal long chain polyunsaturated fatty acid (LCPUFA) status during pregnancy
      was found to be positively associated with bone mass in the offspring at age 4
      years. The findings suggest that variation in intrauterine exposure to n-3 and n
      6 LCPUFAs may have potential consequences for skeletal development. INTRODUCTION:
      Maternal diet in pregnancy has been linked to childhood bone mass, but the
      mechanisms and nutrients involved are uncertain. Long-chain polyunsaturated fatty
      acids (LCPUFAs) have been shown to affect bone metabolism, but the relationship
      between maternal fatty acid status and bone mass in the offspring remains
      unknown. METHODS: We evaluated the association between maternal LCPUFA status in
      late pregnancy (34 weeks gestation) and bone density in their children at age 4
      years within 727 mother-child pairs taking part in the Southampton Women's
      Survey. RESULTS: Concentrations of the n-3 LCPUFA component of maternal plasma
      phosphatidylcholine were positively associated with a number of bone mineral
      measures at the age of 4 years; these associations persisted after adjustment for
      maternal body build, walking speed and infant feeding. Relationships were most
      evident for eicosapentaenoic acid (r = 0.09, p = 0.02 for whole body areal bone
      mineral density [aBMD] and r = 0.1, p = 0.008 for lumbar spine aBMD) and for
      docosapentaenoic acid (r = 0.09, p = 0.02 for whole body aBMD and r = 0.12, p =
      0.002 for lumbar spine aBMD). CONCLUSIONS: These findings suggest that variation
      in early exposure to n-3 and n-6 LCPUFA may have potential consequences for bone
      development and that the effects appear to persist into early childhood.

PMID- 22159751
TI  - Racial and ethnic disparities in outcomes with radiation therapy for rectal
      adenocarcinoma.
AB  - BACKGROUND: Race/ethnicity may modify cancer outcomes and manifest as survival
      disparities for patients with rectal cancer. Our objective was to determine
      whether disparate rectal cancer outcomes result from variable efficacy of
      radiation therapy for major racial/ethnic groups. METHODS: The Los Angeles County
      Cancer Surveillance Program (CSP) identified patients with rectal adenocarcinoma
      between the years 1988 and 2006. Patients who underwent curative-intent surgery
      were grouped by race/ethnicity and by receipt (yes vs. no) and timing
      (neoadjuvant vs. adjuvant) of radiation therapy. The impact of receipt and timing
      of radiation therapy on overall survival was then assessed. RESULTS: Of 4,961
      patients in CSP, 2,229 (45%) received radiation therapy. Overall, there was no
      difference in survival among patients according to receipt of radiation therapy.
      We then examined the radiation cohort, wherein 919 (41%) and 1,310 (59%) patients
      received neoadjuvant or adjuvant radiation, respectively. Overall, patients who
      received neoadjuvant compared to adjuvant radiation had improved survival (median
      survival (MS), 9.4 vs. 6.8 years, respectively; p < 0.001). Among those patients
      who received neoadjuvant radiation, whites, Hispanics, and Asians had
      significantly longer survival than blacks (MS, 10.4, 10.4, and 10.4 vs. 4.4
      years, respectively; p = 0.003). On multivariate analysis, race/ethnicity was an
      independent predictor of survival (p = 0.001). CONCLUSIONS: To our knowledge,
      this is the first study examining the efficacy of radiation therapy for
      racial/ethnic groups with rectal cancer. Disparate outcomes were observed for the
      administration of radiation therapy for select racial/ethnic groups. The reasons
      for these disparities in outcomes should be investigated to better optimize
      radiation therapy for patients with rectal cancer.

PMID- 22159752
TI  - COX-2-independent induction of apoptosis by celecoxib and polyamine naphthalimide
      conjugate mediated by polyamine depression in colorectal cancer cell lines.
AB  - BACKGROUND: Polyamine metabolism is an intriguing tumor therapeutic target. The
      present study was designed to assess the synergistic antitumor effects of NPC-16,
      a novel polyamine naphthalimide conjugate, with celecoxib and to elucidate the
      mechanism of these effects on human colorectal cancer cells. METHODS: Cell
      proliferation was assessed by the MTT assay. Cell apoptosis and mitochondria
      membrane potential were evaluated by high content screening analysis.
      Intracellular polyamine content was detected by HPLC. Protein expression was
      detected by western blot analysis. RESULTS: The co-treatment with celecoxib
      enhanced NPC-16-induced apoptosis in HCT116 (COX-2 no expression), HT29 (COX-2
      higher expression) and Caco-2 (COX-2 higher expression) colorectal cancer cells,
      which was mediated by the elevated NPC-16 uptake via the effect of celecoxib on
      polyamine metabolism, including the up-regulated spermidine/spermine N(1)
      acetyltransferase (SSAT) activity and reduced intracellular polyamine levels. The
      presence of celecoxib does not result in obviously different effect on the NPC-16
      triggered apoptosis in diverse COX-2 expressed colorectal cell lines, suggesting
      that COX-2 was not one vital factor in the apoptotic mechanism. Furthermore, this
      synergistic apoptosis was involved in the PKB/AKT signal pathway, Bcl-2 and
      caspase family members. Z-VAD-FMK, a cell permeable pan caspase inhibitor, almost
      completely inhibited celecoxib and NPC-16 co-induced apoptosis, indicating that
      this apoptosis was caspase dependent. CONCLUSIONS: Co-treatment of celecoxib and
      NPC-16 could induce colorectal cancer cell apoptosis via COX-2-independent and
      caspase-dependent mechanisms. The combination therapy with these agents might
      provide a novel therapeutic model for colorectal cancer.

PMID- 22159753
TI  - Unimolecular and bimolecular binding system for the prediction of CYP2D6-mediated
      metabolism.
AB  - We have developed a template system for the prediction of CYP2D6-mediated
      metabolism of compounds. The system is composed of two types of two-dimensional
      templates (templates A and B), which were generated from mutually occupied areas
      of typical CYP2D6 substrates. The areas of templates are expressed as hexagonal
      blocks for application to the two-dimensional structures of chemicals.
      Experiments with 93 reactions with 69 typical substrates indicated the necessity
      for two similar but distinct shapes for template A (A1 and A2) for optimal
      placement. A frequently occupied area for substrates in template A1 was defined
      as a trigger area in which to capture a substrate for initiation of metabolism.
      Another frequently occupied area was found near the site of metabolism in
      template B. Both frequently occupied areas are linked to a pinching area.
      Occupancy of substrates on two template areas is suggested to be essential for
      the metabolism of CYPD6 substrates. In cases of CYP2D6 substrates without
      simultaneous occupancy of both areas, bimolecular placement, in which two
      molecules are placed coordinately, is proposed. Metabolism of small molecules,
      including naphthalene and quinoline, became explainable with the use of this
      idea. Validation of this template system with the use of both good and poor
      CYP2D6 substrates indicated clear advantages of the present system as a tool for
      drug modification, in addition to enabling highly accurate estimation of the site
      of metabolism.

PMID- 22159754
TI  - A mixed model QTL analysis for sugarcane multiple-harvest-location trial data.
AB  - Sugarcane-breeding programs take at least 12 years to develop new commercial
      cultivars. Molecular markers offer a possibility to study the genetic
      architecture of quantitative traits in sugarcane, and they may be used in marker
      assisted selection to speed up artificial selection. Although the performance of
      sugarcane progenies in breeding programs are commonly evaluated across a range of
      locations and harvest years, many of the QTL detection methods ignore two- and
      three-way interactions between QTL, harvest, and location. In this work, a
      strategy for QTL detection in multi-harvest-location trial data, based on
      interval mapping and mixed models, is proposed and applied to map QTL effects on
      a segregating progeny from a biparental cross of pre-commercial Brazilian
      cultivars, evaluated at two locations and three consecutive harvest years for
      cane yield (tonnes per hectare), sugar yield (tonnes per hectare), fiber percent,
      and sucrose content. In the mixed model, we have included appropriate
      (co)variance structures for modeling heterogeneity and correlation of genetic
      effects and non-genetic residual effects. Forty-six QTLs were found: 13 QTLs for
      cane yield, 14 for sugar yield, 11 for fiber percent, and 8 for sucrose content.
      In addition, QTL by harvest, QTL by location, and QTL by harvest by location
      interaction effects were significant for all evaluated traits (30 QTLs showed
      some interaction, and 16 none). Our results contribute to a better understanding
      of the genetic architecture of complex traits related to biomass production and
      sucrose content in sugarcane.

PMID- 22159756
TI  - Breeding maize as biogas substrate in Central Europe: I. Quantitative-genetic
      parameters for testcross performance.
AB  - Biofuels have gained importance recently and the use of maize biomass as
      substrate in biogas plants for production of methane has increased tremendously
      in Germany. The objectives of our research were to (1) estimate variance
      components and heritability for different traits relevant to biogas production in
      testcrosses (TCs) of maize, (2) study correlations among traits, and (3) discuss
      strategies to breed maize as a substrate for biogas fermenters. We evaluated 570
      TCs of 285 diverse dent maize lines crossed with two flint single-cross testers
      in six environments. Data were recorded on agronomic and quality traits,
      including dry matter yield (DMY), methane fermentation yield (MFY), and methane
      yield (MY), the product of DMY and MFY, as the main target trait. Estimates of
      variance components showed general combining ability (GCA) to be the major source
      of variation. Estimates of heritability exceeded 0.67 for all traits and were
      even much greater in most instances. Methane yield was perfectly correlated with
      DMY but not with MFY, indicating that variation in MY is primarily determined by
      DMY. Further, DMY had a larger heritability and coefficient of genetic variation
      than MFY. Hence, for improving MY, selection should primarily focus on DMY rather
      than MFY. Further, maize breeding for biogas production may diverge from that for
      forage production because in the former case, quality traits seem to be of much
      lower importance.

PMID- 22159755
TI  - Bin mapping of tomato diversity array (DArT) markers to genomic regions of
      Solanum lycopersicum * Solanum pennellii introgression lines.
AB  - Marker-trait association studies in tomato have progressed rapidly due to the
      availability of several populations developed between wild species and
      domesticated tomato. However, in the absence of whole genome sequences for each
      wild species, molecular marker methods for whole genome comparisons and fine
      mapping are required. We describe the development and validation of a diversity
      arrays technology (DArT) platform for tomato using an introgression line (IL)
      population consisting of wild Solanum pennellii introgressed into Solanum
      lycopersicum (cv. M82). A tomato diversity array consisting of 6,912 clones from
      domesticated tomato and twelve wild tomato/Solanaceous species was constructed.
      We successfully bin-mapped 990 polymorphic DArT markers together with 108 RFLP
      markers across the IL population, increasing the number of markers available for
      each S. pennellii introgression by tenfold on average. A subset of DArT markers
      from ILs previously associated with increased levels of lycopene and carotene
      were sequenced, and 44% matched protein coding genes. The bin-map position and
      order of sequenced DArT markers correlated well with their physical position on
      scaffolds of the draft tomato genome sequence (SL2.40). The utility of sequenced
      DArT markers was illustrated by converting several markers in both the S.
      pennellii and S. lycopersicum phases to cleaved amplified polymorphic sequence
      (CAPS) markers. Genotype scores from the CAPS markers confirmed the genotype
      scores from the DArT hybridizations used to construct the bin map. The tomato
      diversity array provides additional "sequence-characterized" markers for fine
      mapping of QTLs in S. pennellii ILs and wild tomato species.

PMID- 22159757
TI  - Breeding maize as biogas substrate in Central Europe: II. Quantitative-genetic
      parameters for inbred lines and correlations with testcross performance.
AB  - Breeding maize for use as a biogas substrate (biogas maize) has recently gained
      considerable importance. To optimize hybrid breeding programs, information about
      line per se performance (LP) of inbreds and its relation to their general
      combining ability (GCA) is required. The objectives of our research were to (1)
      estimate variance components and heritability of LP for agronomic and quality
      traits relevant to biogas production, (2) study correlations among traits as well
      as between LP and GCA, and (3) discuss implications for breeding of biogas maize.
      We evaluated 285 diverse dent maize inbred lines in six environments. Data were
      recorded on agronomic and quality traits, including dry matter yield (DMY),
      methane fermentation yield (MFY), and their product, methane yield (MY), as the
      main target trait. In agreement with observations made for GCA in a companion
      study, variation in MY was mainly determined by DMY. MFY, which showed moderate
      correlation with lignin but only weak correlation with starch, revealed only low
      genotypic variation. Thus, our results favor selection of genotypes with high DMY
      and less focus on ear proportion for biogas maize. Genotypic correlations between
      LP and GCA [r (g) (LP, GCA)] were highest (>=0.94) for maturity traits (days to
      silking, dry matter concentration) and moderate (>=0.65) for DMY and MY.
      Multistage selection is recommended. Selection for GCA of maturity traits, plant
      height, and to some extent also quality traits and DMY on the level of LP looks
      promising.

PMID- 22159758
TI  - Molecular tagging and validation of microsatellite markers linked to the low
      germination stimulant gene (lgs) for Striga resistance in sorghum [Sorghum
      bicolor (L.) Moench].
AB  - Striga is a devastating parasitic weed in Africa and parts of Asia. Low Striga
      germination stimulant activity, a well-known resistance mechanism in sorghum, is
      controlled by a single recessive gene (lgs). Molecular markers linked to the lgs
      gene can accelerate development of Striga-resistant cultivars. Using a high
      density linkage map constructed with 367 markers (DArT and SSRs) and an in vitro
      assay for germination stimulant activity towards Striga asiatica in 354
      recombinant inbred lines derived from SRN39 (low stimulant) * Shanqui Red (high
      stimulant), we precisely tagged and mapped the lgs gene on SBI-05 between two
      tightly linked microsatellite markers SB3344 and SB3352 at a distance of 0.5 and
      1.5 cM, respectively. The fine-mapped lgs region was delimited to a 5.8 cM
      interval with the closest three markers SB3344, SB3346 and SB3343 positioned at
      0.5, 0.7 and 0.9 cM, respectively. We validated tightly linked markers in a set
      of 23 diverse sorghum accessions, most of which were known to be Striga
      resistant, by genotyping and phenotyping for germination stimulant activity
      towards both S. asiatica and S. hermonthica. The markers co-segregated with
      Striga germination stimulant activity in 21 of the 23 tested lines. The lgs locus
      similarly affected germination stimulant activity for both Striga species. The
      identified markers would be useful in marker-assisted selection for introgressing
      this trait into susceptible sorghum cultivars. Examination of the sorghum genome
      sequence and comparative analysis with the rice genome suggests some candidate
      genes in the fine-mapped region (400 kb) that may affect strigolactone
      biosynthesis or exudation. This work should form a foundation for map-based
      cloning of the lgs gene and aid in elucidation of an exact mechanism for
      resistance based on low Striga germination stimulant activity.

PMID- 22159759
TI  - Extending the rapeseed gene pool with resynthesized Brassica napus II: Heterosis.
AB  - Hybrid breeding relies on the combination of parents from two differing heterotic
      groups. However, the genetic diversity in adapted oilseed rape breeding material
      is rather limited. Therefore, the use of resynthesized Brassica napus as a
      distant gene pool was investigated. Hybrids were derived from crosses between 44
      resynthesized lines with a diverse genetic background and two male sterile winter
      oilseed rape tester lines. The hybrids were evaluated together with their parents
      and check cultivars in 2 years and five locations in Germany. Yield, plant
      height, seed oil, and protein content were monitored, and genetic distances were
      estimated with molecular markers (127 polymorphic RFLP fragments). Resynthesized
      lines varied in yield between 40.9 dt/ha and 21.5 dt/ha, or between 85.1 and
      44.6% of check cultivar yields. Relative to check cultivars, hybrids varied from
      91.6 to 116.6% in yield and from 94.5 to 103.3% in seed oil content. Mid-parent
      heterosis varied from -3.5 to 47.2% for yield. The genetic distance of parental
      lines was not significantly correlated with heterosis or hybrid yield. Although
      resynthesized lines do not meet the elite rapeseed standards, they are a valuable
      source for hybrid breeding due to their large distance from present breeding
      material and their high heterosis when combined with European winter oilseed
      rape.

PMID- 22159760
TI  - TRAIL is involved in CpG ODN-mediated anti-apoptotic signals.
AB  - Synthetic oligodeoxynucleotides (ODNs) with the CpG-motifs are recognized by toll
      like receptor 9 (TLR9), which elicits an immune response. Serum starvation of
      Raw264.7 cells increased tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) expression. However, treatment with CpG ODN reduced TRAIL expression as
      well as apoptosis by serum starvation. In serum starved cells, TLR9 inhibitors
      recovered the decreasing TRAIL expression and sub-G1 accumulation by CpG ODN. CpG
      ODN-regulated anti-apoptotic signals which were dependent on the Akt-FoxO3a
      signaling pathway. CpG ODNs activated Akt and inactivated FoxO3a in serum starved
      cells. Knockdown of FoxO3a by siRNA decreased TRAIL expression and apoptosis in
      serum-starved cells. In contrast, FoxO3a overexpression increased apoptosis by
      serum starvation, and CpG ODNs blocked these effects through TRAIL expression.
      LY294002, a PI3K-Akt inhibitor, blocked the CpG ODN effect of TRAIL expression
      and the sub-G1 population in serum starved cells. In contrast, overexpression of
      wild-type Akt reduced additional sub-G1 cells both in non-CpG ODN- and CpG ODN
      treated cells. Taken together, these results demonstrate the involvement of Akt
      FoxO3a signaling in TLR9-mediated downregulation of TRAIL and anti-apoptotic
      signals.

PMID- 22159761
TI  - Locally produced insulin-like growth factor-1 by orbital fibroblasts as
      implicative pathogenic factor rather than systemically circulated IGF-1 for
      patients with thyroid-associated ophthalmopathy.
AB  - BACKGROUND: To determine the correlation between clinical activity scores (CAS)
      of thyroid-associated ophthalmology (TAO) patients and their locally produced
      and/or systemically circulating insulin-like growth factor-1 (IGF-1), and to
      assess the possible pathogenic role of IGF-1 in TAO. METHODS: Eighteen patients
      with TAO, and 16 age- and gender-matched controls were included in the present
      study. Among them, orbital tissue surgically collected from five TAO patients and
      five healthy controls was used for orbital fibroblasts (OFs) culture and in vitro
      study. Total and free IGF-1 in serum levels were determined by an ELISA kit for
      all the participants in this study. The IGF-1 concentration in culture media of
      OFs was determined using a noncompetitive time-resolved radioimmunoassay kit. The
      effect of octreotide (OCT), a somatostatin analog, on proliferation of OFs was
      assessed using the MTT assay. IGF-1 mRNA levels were measured by real-time
      polymerase chain reaction (PCR). RESULTS: Cultured OFs from both TAO patients and
      normal donors secreted IGF-1, and the secretion continued over a 72 hour period
      in vitro. IGF-1 secretion by OFs was elevated in the TAO group. Both the elevated
      secretion of IGF-1 and proliferation of OFs from TAO patients could be inhibited
      by OCT. Result of quantitative PCR showed that IGF-1 mRNA expression by OFs in
      TAO patients was up-regulated more than 2-fold compared with normal controls (P <
      0.05), and this up-regulation was prevented by OCT treatment. Total and free
      serum IGF-1 levels in TAO patients were similar to those of normal controls.
      However, the IGF-1 level in cultured medium of OFs from TAO patients, but not
      serum levels of IGF-1, was positively correlated with CAS (r = 0.97, P = 0.017).
      CONCLUSIONS: Local production of IGF-1 by cultured OFs may be positively
      correlated with CAS, whereas systemically circulating IGF-1 may remain unchanged
      in TAO patients. Thus, locally produced IGF-1 may develop a role in the
      pathogenesis of TAO in an autocrine or paracrine fashion. The inhibitory effect
      of OCT on proliferating and IGF-1 mRNA levels of cultured OFs from TAO patients
      may be used as the mechanistic explanation for somatostatin analog as a valuable
      option in the treatment of TAO.

PMID- 22159762
TI  - Expecting to lift a box together makes the load look lighter.
AB  - The action abilities of an individual observer modulate his or her perception of
      spatial properties of the environment and of objects. The present study
      investigated how joint action abilities shape perception. Four experiments
      examined how the intention to lift an object with another individual affects
      perceived weight. In Experiments 1, 2a, and 2b, participants judged the perceived
      weight of boxes while expecting to lift them either alone or with a co-actor. In
      Experiment 3, the co-actor was healthy or injured. Participants intending to lift
      a box with a co-actor perceived the box as lighter than participants intending to
      lift the same box alone, provided that the co-actor appeared healthy and
      therefore capable of helping. These findings suggest that anticipated effort
      modulates the perception of object properties in the context of joint action. We
      discuss implications for the role of action prediction and action simulation
      processes in social interaction.

PMID- 22159763
TI  - Response-mode shifts during sequence learning of macaque monkeys.
AB  - Incidental sequence learning has been conceptualized as involving a shift from
      stimulus-based to plan-based performance (e.g., Tubauet et al. in Journal of
      Experimental Psychology: General 136:43-63, 2007). We analyzed the response time
      (RT) data of two macaque monkeys that were trained for thousands of trials on a
      sequential reaching task in a study by Matsuzaka et al. in Journal of
      Neurophysiology 97, 1819-1832 (2007). The animals learned to respond predictively
      to a repeating 3-element sequence. During a transitional period, RT distributions
      were bimodal, indicating that the animals alternated between two processing
      modes. An analysis of trial-to-trial mode shifting probabilities provided
      preliminary evidence for a strategic process.

PMID- 22159764
TI  - Concept of a thin film memory transistor based on ZnO nanoparticles insulated by
      a ligand shell.
AB  - In this work, we report on the synthesis and the electrical properties of ZnO
      nanoparticles, which differ in their organic shell. The introduction of a 2
      ethylhexanoate shell instead of a common acetate shell has an impact on the
      accessible size of the ZnO nanoparticles and changes the electrical properties of
      thin films in transistors. While acetate covered ZnO particles behave as a
      semiconductor with an electron mobility of 0.38 cm(2) V(-1) s(-1), the 2
      ethylhexanoate ligand shell inhibits a charge transport resulting in insulating
      films (with an average epsilon(r) = 9.4). These films can be reconverted to
      semiconductive layers by removing the ligand shell with oxygen plasma treatment
      or they can be used as a solution processed dielectric layer in organic
      transistors. Its use as dielectric allows low voltage device operation and shows
      potential application as a charge storage layer as needed in non-volatile memory
      transistors.

PMID- 22159765
TI  - Body circumferences are predictors of weight adjusted resting energy expenditure
      in older people.
AB  - OBJECTIVE: To evaluate predictors of resting energy expenditure (REE) in older
      people which are more comfortable for them than indirect calorimetry and which
      are suitable for field studies. DESIGN: Cross-sectional study. SETTING:
      Department of Human Biology, Kiel University. PARTICIPANTS: 100 (51 males, 49
      females) healthy independently-living normal-weight (BMI, males 26.0+/-2.67
      kg/m2, females 25.0+/-3.29 kg/m2) Germans, aged 60-83 years. MEASUREMENTS: REE,
      body composition, anthropometry, peak expiratory flow rate (PEF), and physical
      activity level were determined using indirect calorimetry, bioimpedance analysis,
      anthropometrics, peak-flow-meter, and standardized questionnaire, respectively.
      Stepwise linear multiple regression analysis was performed with REE or weight
      adjusted REE as dependent variables. Independent variables were body height,
      weight, body mass index (BMI), waist circumference, abdomen circumference, hip
      circumference, waist-to-hip ratio (WHR), lean body mass (LBM), PEF, and physical
      activity level. RESULTS: The only significant predictor of REE was LBM in males
      and BMI in females. Trunk circumferences emerged as strong predictors of weight
      adjusted REE. Abdomen circumference and hip circumference explained in males and
      females 69% and 70% of variation in adjusted REE, respectively. Weaker predictors
      were LBM in males (R2 increased from 0.69 to 0.80) as well as body height and BMI
      in females (R2 increased from 0.70 to 0.91). Waist circumference, WHR, physical
      activity level, and PEF were no significant determinants of adjusted REE.
      CONCLUSION: These findings demonstrate that trunk circumferences, but not WHR,
      are very strong predictors of weight adjusted REE in non-geriatric older people.
      This implies that the sex-specific use of abdomen or hip circumference in
      combination with LBM or body height and BMI seems to be well sufficient to
      predict weight adjusted REE in the aged. These measures might also be of clinical
      relevance, because they are more comfortable for older sick people than indirect
      calorimetry. Further studies are needed to test the applicability of the
      prediction equations to frail older populations.

PMID- 22159766
TI  - Validity of retrospective diet history: assessing recall of midlife diet using
      food frequency questionnaire in later life.
AB  - OBJECTIVES: Limited information exists on the validity of dietary information
      given by elderly people on their past diet. Here we test the relative validity of
      a food frequency questionnaire asking older persons about their midlife diet.
      DESIGN: Retrospective food intake of 56-72-year-old subjects was estimated using
      a food frequency questionnaire designed for the AGES-Reykjavik Study (AGES-FFQ),
      an epidemiological study of older individuals. Results were compared with
      detailed dietary data gathered from the same individuals 18-19 years previously,
      i.e., in midlife, as part of a national cohort. Spearman correlation and cross
      classifications were used to assess the ability of the AGES-FFQ to rank subjects
      according to their intake. SETTING: Nationwide, Iceland. PARTICIPANTS: Subjects,
      born 1937-1952 (n=174), who participated in the 1990 Icelandic National Dietary
      Survey. MEASUREMENTS: Dietary intake, estimated by the AGES-FFQ (2008-2009), and
      dietary history obtained from the 1990 Icelandic National Dietary Survey as a
      reference method. RESULTS: The strongest correlation between the AGES-FFQ and the
      reference method was found for cod liver oil, r=0.53, p<0.001 and r=0.56,
      p<0.001, for men and women, respectively. For men the corresponding correlation
      coefficient for milk and dairy products was r=0.43, p<0.001. The correlation
      coefficients were lower but within a reasonably acceptable range (r=0.26-0.40)
      for meat, fish and potatoes for both genders, as well as fresh fruits and
      milk/dairy products for women and whole-wheat bread, oatmeal/muesli and
      blood/liver-sausage for men. No correlation was found between the AGES-FFQ and
      the dietary history for rye bread and vegetable consumption. Subjects were
      categorized into five groups according to level of consumption by the two
      methods. Cross-classification showed that 16-59% were classified into same group
      and 43-91% into same or adjacent group, 0-14% were grossly misclassified into
      opposite groups. CONCLUSION: The AGES-FFQ on midlife diet was found suitable to
      rank individuals by their intake of several important food groups.

PMID- 22159767
TI  - A simple food quality index predicts mortality in elderly Taiwanese.
AB  - OBJECTIVES: To assess the relative predictive ability for mortality of the
      Overall Dietary Index-Revised (ODI-R) and the Dietary Diversity Score (DDS) among
      representative Taiwanese aged 65 and older. DESIGN: Prospective cohort. SETTING:
      The Elderly Nutrition and Health Survey in Taiwan during 1999-2000. PARTICIPANTS:
      One thousand seven hundred forty three (860 men and 883 women). MEASUREMENTS:
      Dietary quality measures, the ODI-R (0-100) and DDS (0-6) were based on 24-hour
      dietary recall and a food frequency questionnaire at baseline. Death by National
      Death Registry up to 2008 was the outcome measure. RESULTS: During follow-up, 624
      subjects died. The survivors had both significantly higher (P <0.001) ODI-R (66.9
      vs. 63.6) and DDS (4.69 vs. 4.30) than the deceased. The two indices were
      correlated (r=0.46). After adjustment for potential covariates, the hazard ratios
      (HR) (95% CI) were 0.63 (0.42-0.97), 0.71 (0.49-1.04) and 0.53 (0.37-0.76) for
      those whose ODI-R scores were 60-65, 65-70, >70, respectively, compared to those
      whose ODI-R scores were > 50 (P for trend <0.001). For DDS, the multi-variable
      HRs (95% CI) were 0.74 (0.55-1.00), 0.52 (0.38-0.72) and 0.50 (0.31-0.81) for
      those whose DDS were 4, 5, 6, respectively, compared to those whose DDS were <=3
      (P for trend<0.001). Total cancer, diabetes mortalities and pneumonia were
      similarly benefited according to trends. CONCLUSION: ODI-R >= 60, and DDS >= 4
      are predictors of all-cause and cause-specific mortalities. Of the two, DDS is
      the more predictive. Nutrition policy could be informed and clinical practice
      enhanced by these population relevant food-health relationships.

PMID- 22159769
TI  - Pro-dromal sarcopenia.

PMID- 22159770
TI  - Sarcopenia: biomarkers and imaging (International Conference on Sarcopenia
      research).

PMID- 22159768
TI  - Health and nutrition promotion program for patients with dementia (NutriAlz):
      cluster randomized trial.
AB  - OBJECTIVE: To assess the effectiveness of health and nutrition program (NutriAlz)
      versus usual care on functional level in elderly people with dementia living at
      home, as well as on clinical practice related to nutrition and on the caregiver's
      burden. DESIGN: Cluster randomized multi-centre study with one-year follow-up.
      SETTING: 11 Alzheimer outpatients and day care centres (Barcelona, Spain).
      PARTICIPANTS: Nine hundred and forty six home-living Alzheimer patients with
      identified caregiver were consecutively recruited (intervention group: 6 centres,
      448 patients vs control group: 5 centres, 498 patients). INTERVENTION: The
      intervention was a teaching and training intervention on health and nutrition
      program, NutriAlz, directed both to physician and main caregiver, as well as
      persons affected by Alzheimer's disease or other dementias, including a
      standardised protocol for feeding and nutrition. MAIN OUTCOME MEASURES: The main
      outcome measure was the reduction in the loss of autonomy (Activities of daily
      living (ADL/IADL) scales) assessed at 6 and 12 months. Secondary outcomes
      measures were Improvement in nutritional status (Mini Nutritional Assessment
      (MNA), BMI, and weight changes), and caregiver burden (Zarit scale). RESULTS: The
      one-year assessment was completed for 293 patients (65.4%) in the intervention
      group and 363 patients (72.9%) in the control group (usual care). The annual rate
      of ADL change was -0.83 vs -0.62 (p=0.984), and the caregiver's subjective burden
      0.59 vs 2.36 (p=0.681) in intervention and control group, respectively. MNA,
      however, showed an improvement (+0.46 vs -0.66, p=0.028), suggesting an effective
      nutritional behaviour. CONCLUSION: The NutriAlz program had no effect on
      functional decline in Alzheimer disease patients living at home over one year,
      but reduced the risk for malnutrition, as recommendations concerning diet and
      exercise were provided.

PMID- 22159771
TI  - Are current definitions of sarcopenia applicable for older Chinese adults?
AB  - This study aims to explore whether the current definitions of sarcopenia are
      applicable to the older Chinese population. Participants were 783 Chinese adults
      recruited from four regions in Mainland China: Jinan, Guangzhou, Xi'an, and
      Chengdu. Body composition was measured by dual energy x-ray absorptiometry.
      Handgrip strength, body weight, and height were measured by trained technicians,
      and demographic data were collected through questionnaires. Relative appendicular
      skeletal muscle, skeletal muscle index (SMI=100 * skeletal muscle mass/ body
      mass) and residuals methods were applied to identify sarcopenia. Compared with
      young adults, no significant decrease was found in the relative appendicular
      skeletal muscle (ASM/height2) in older adults. If the criterion of two standard
      deviations below the mean value of ASM/height2 in young adults is used, none of
      older adults in this study could be diagnosed with sarcopenia. In addition,
      compared with the ASM/height2 and residuals methods, SMI shows higher
      discriminating power in the identifying persons with low handgrip strength. The
      data suggest that ASM/height2 method may not be appropriate for diagnosis of
      sarcopenia in Chinese population. However, whether SMI is a better choice remains
      inconclusive. Prospective studies are needed to clearly define sarcopenia in
      Chinese population.

PMID- 22159772
TI  - The prevalence of frailty syndrome in an older population from Spain. The Toledo
      Study for Healthy Aging.
AB  - OBJECTIVE: To assess the prevalence of the frailty syndrome and its associated
      variables among the older adult population in the province of Toledo (Spain).
      METHODS: Data were taken from the Toledo Study for Healthy Aging, a population
      based study conducted on 2,488 individuals aged 65 years and older. Study
      participants were selected by a two-stage random sampling from the municipal
      census of Toledo, covering both institutionalized and community dwelling persons
      from rural and urban settings. Data were collected from 2006 to 2009, and
      included information on social support, activities of daily living, comorbidity,
      physical activity, quality of life, depressive symptoms, and cognitive function.
      In addition, a nurse collected anthropometric data, conducted tests of physical
      performance (walk speed, upper and lower extremities strength, and the stand-and
      sit from a chair test) and obtained a blood sample. The diagnosis of the frailty
      syndrome was based on the Fried criteria (weakness, low speed, low physical
      activity, exhaustion, and weight loss). RESULTS: In total, 41.8% (95% confidence
      interval [CI] 39.4-44.2%) of the study participants were prefrail, and 8.4% (95%
      CI 7.1-9.8%) were frail. There were no differences in the prevalence of frailty
      by sex, level of education, occupation, marital status, or place of residence.
      The frequency of the frailty syndrome increased with age, and was higher in those
      with disability, depression, hip fracture and other comorbidity, such as
      cardiovascular disease and disorders of the central nervous system. CONCLUSIONS:
      The prevalence of the frailty syndrome in older Spanish adults is high and
      similar to that reported in other populations in the Mediterranean basin.

PMID- 22159773
TI  - Physical frailty in older adults is associated with metabolic and atherosclerotic
      risk factors and cognitive impairment independent of muscle mass.
AB  - OBJECTIVE: Metabolic and atherosclerotic diseases are known risk factors for
      disability in old age, and can result in sarcopenia as well as cognitive
      impairment, which are both components of frailty syndrome. As muscle loss
      increases with ageing, it is unclear whether muscle loss per se, or the diseases
      themselves, are the underlying cause of physical frailty in those suffering from
      these diseases. We tested the hypothesis that metabolic and atherosclerotic
      diseases and cognitive impairment are associated with physical frailty
      independent of muscle loss in old age, and further examined their impact on the
      relationship between physical frailty and mortality. DESIGN: Prospective.
      SETTING: Community. PARTICIPANTS: 4000 community dwelling Chinese elderly >=65
      years. MEASUREMENTS: Diabetes, hypertension, stroke, heart disease, cognitive
      impairment, smoking, physical activity, waist hip ratio (WHR) and ankle-brachial
      index (ABI)) were recorded. Physical frailty measurements (grip-strength, chair
      stands, stride length and 6-metre walks) were summarized into a composite frailty
      score (0-20), 0 being the most frail) according to quartiles of performance.
      Appendicular muscle mass (ASM) was measured using dual X-ray absorptiometry.
      Relationships between the score and covariates were analyzed. Cox regression was
      used to study the impact of metabolic and atnerosclerotic risk factors on the
      relationship between physical frailty and 6-year mortality. RESULTS: After
      adjustment for ASM, all metabolic diseases and indexes, and cognitive impairment
      were significantly associated with the composite physical frailty score in
      univariate analysis. In multivariate analysis, cognitive impairment, high WHR,
      diabetes, stroke and heart disease were all independently associated with higher
      physical frailty with adjustment for age, physical activity level and ASM.
      Hypertension was associated with physical frailty in men but not in women. In Cox
      regression, increased physical frailty was associated with higher 6-year
      mortality. The impact of metabolic and atherosclerotic risk factors was however
      only modest after adjustment for age and cognitive function. CONCLUSION:
      Metabolic and atherosclerotic diseases and high WHR, was associated with physical
      frailty, independent of their adverse effect on cognitive function and muscle
      mass.

PMID- 22159774
TI  - Transitions in cognitive status in relation to frailty in older adults: a
      comparison of three frailty measures.
AB  - OBJECTIVES: Cognitive decline is related to frailty. Frailty can be
      operationalized in different ways, which have an unknown impact on the estimation
      of risk. Here, we compared 3 frailty measures in relation to cognitive changes
      and mortality in the Canadian Study of Health and Aging (CSHA). DESIGN:
      Prospective population-based study, with 5 year follow up. PARTICIPANTS/SETTING:
      2,305 subjects aged 70+ years. METHODS: For each participant, cognitive status
      was measured by the errors in the Modified Mini-Mental State Examination (3MS)
      score. Three frailty measures were used: a Frailty Index based on the
      Comprehensive Geriatric Assessment (FI-CGA) evaluated from 47 potential deficits,
      a Clinical Frailty Score and the Fried frailty phenotype. Multivariate Poisson
      regression and multivariate logistic regression were used to examine the
      association between baseline cognitive errors and frailty and death,
      respectively, while controlling for possible confounders (age, sex, education,
      and baseline cognitive status). RESULTS: Changes in cognitive status were
      strongly associated with baseline cognition and frailty, however defined. In
      multivariate models adjusted for age, sex and education, each frailty measure was
      associated with cognitive decline and with mortality. The frailest people (from
      the highest FI-CGA tertile) rarely showed cognitive improvement or stabilization
      (1.5%, 95% CI=0.002%-2.8%) compared with non-frail people (from the lowest
      tertile of the FI-CGA), of whom 27.8% (95% CI=24.5%-31.1%) did not deteriorate.
      CONCLUSIONS: Frail elderly people have an increased risk of cognitive decline.
      All frailty measures allowed quantification of individual vulnerability and
      predict both cognitive changes and mortality.

PMID- 22159775
TI  - The effect of medical nutrition therapy on changes in dietary knowledge and DASH
      diet adherence in older adults with cardiovascular disease.
AB  - OBJECTIVE: To examine the effect of MNT on dietary knowledge of older adults at
      baseline, 6 months and 12 months and to assess the effect of dietary knowledge on
      change in DASH diet adherence from baseline to 12 months. DESIGN: Data for the
      analysis come from a controlled, randomized prospective design conducted from
      2003-2005 with the outcome measures taken pre-, mid-, and post-intervention.
      SETTING: Data were collected from participants in their homes in an urban
      community in North Carolina. PARTICIPANTS: Participants (N=147) were adults aged
      60+ with a diagnosis of hypertension and/or hyperlipidemia. INTERVENTION:
      Intervention recipients received three sessions of MNT throughout the 1 year
      study period. The control group received nutrition information at enrollment.
      MEASUREMENTS: Participants completed a dietary knowledge questionnaire and a 24
      dietary recall at baseline, 6 months, and 12 months. Instrumental variables
      models with participant fixed effects were used to determine the impact of MNT on
      dietary knowledge and dietary knowledge on DASH diet adherence. RESULTS: Among
      those who received MNT, dietary knowledge increased from baseline to twelve
      months (p<.01). Changes in dietary knowledge were not associated with changes in
      DASH adherence from baseline to 12 months (p=0.44). CONCLUSIONS: The MNT
      administered was effective at improving dietary knowledge, but not at improving
      DASH adherence. Three MNT sessions may be insufficient to change behavior.
      Integrating behavioral change theory and cultural sensitivity to MNT may improve
      diet adherence among diverse older adults.

PMID- 22159776
TI  - Serum albumin and hemoglobin are associated with physical function in community
      living older persons in Singapore.
AB  - OBJECTIVES: Albumin and hemoglobin are viewed as markers of nutritional and
      inflammatory status. This study examined the associations of serum albumin and
      hemoglobin with physical function in community-living older adults. DESIGN:
      Population-based cross-sectional and longitudinal study. SETTING: The Singapore
      Longitudinal Aging Studies (SLAS), a community-based study in urban Singapore.
      PARTICIPANTS: 2762 older adults aged 55 and above assessed at baseline, and 1829
      at follow up 1-2 years later. MEASUREMENTS: Serum albumin and hemoglobin,
      Performance Oriented Mobility Assessment (POMA), knee extension strength at
      baseline, and Instrumental Activities of Daily Living (IADL) at baseline and
      follow up. RESULTS: In cross-sectional multivariate analyses that adjusted for
      haemoglobin and other confounders, albumin showed a significant linear
      association (p<0.001) with POMA balance score (b=0.06, SE=0.02) and knee
      extension strength (b=0.70, SE=0.10). Independently of albumin, hemoglobin also
      showed a significant linear association with POMA balance score (b=0.09,
      SE=0.04). In longitudinal analyses, albumin was significantly associated with
      IADL decline (IADL total score drop>=1 during follow-up), OR= 0.92 (0.87 - 0.97),
      p=<0.01. CONCLUSION: The findings suggest that low levels of albumin and
      hemoglobin are potentially useful risk markers of physical functional decline in
      older adults. Further research should investigate whether improvements in the
      levels of albumin and hemoglobin alter the level of functional disability and
      risk of functional decline.

PMID- 22159777
TI  - Combined effect of antioxidant supplementation and resistance training on
      oxidative stress markers, muscle and body composition in an elderly population.
AB  - This study was aimed to examine the effect of vitamin C/E intake alone or
      combined with resistance training on antioxidant/pro-oxidant status, muscle
      strength and body composition in an elderly population. Fifty-seven men and women
      with a mean age of 65.6 +/- 3.8 years were recruited and randomized in a double
      blind fashion into four groups: control-placebo; resistance training (RT);
      vitamins C/E supplementation (AS); AS+RT. Oxidative stress status and metabolic
      and lipid profiles were determined at baseline and after six months. Fat-free
      mass and fat mass measured by DXA were similar at baseline for all groups. At six
      month, there was a significant difference among the groups as a function of
      vitamin E supplementation. Moreover, although there was no effect on pro
      oxidative parameters, a significant effect on body composition was noted, but no
      difference was noted on strength gain. The combination of RT+AS had a positive
      effect on the plasma antioxidant profile but not on the pro-oxidant status.

PMID- 22159778
TI  - Discovering pathways of sarcopenia in older adults: a role for insulin resistance
      on mitochondria dysfunction.
AB  - The precise cause of sarcopenia, skeletal muscle loss and strength, in older
      persons is unknown. However, there is a strong evidence for muscle loss due to
      insulin resistance as well as mitochondrial dysfunction over aging. Considering
      that epidemiological studies have underlined that insulin resistance may have a
      specific role on skeletal muscle fibre atrophy and mitochondrial dysfunction has
      also been extensively shown to have a pivotal role on muscle loss in older
      persons, a combined pathway may not be ruled out. Considering that there is
      growing evidence for an insulin-related pathway on mitochondrial signaling, we
      hypothesize that a high degree of insulin resistance will be associated with the
      development of sarcopenia through specific alterations on mitochondrial
      functioning. This paper will highlight recent reviews regarding the link between
      skeletal muscle mitochondrial dysfunction and insulin resistance. We will
      specifically emphasize possible steps involved in sarcopenia over aging,
      including potential biomolecular mechanisms of insulin resistance on
      mitochondrial functioning.

PMID- 22159779
TI  - Dietary antioxidant intake is associated with the prevalence but not incidence of
      age-related hearing loss.
AB  - OBJECTIVES: Diet is one of the few modifiable risk factors for age-related
      hearing loss. We aimed to examine the link between dietary and supplement intakes
      of antioxidants, and both the prevalence and 5-year incidence of measured hearing
      loss. DESIGN: Cross-sectional and 5-year longitudinal analyses. SETTING: Blue
      Mountains, Sydney, Australia. PARTICIPANTS: 2,956 Blue Mountains Hearing Study
      participants aged 50+ at baseline, examined during 1997-9 to 2002-4.
      MEASUREMENTS: Age-related hearing loss was measured and defined as the pure-tone
      average of frequencies 0.5, 1.0, 2.0 and 4.0 kHz >25 dB HL. Dietary data were
      collected in a semi-quantitative food frequency questionnaire, and intakes of
      alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein and zeaxanthin;
      lycopene; vitamins A, C and E; iron and zinc were calculated. RESULTS: After
      adjusting for age, sex, smoking, education, occupational noise exposure, family
      history of hearing loss, history of diagnosed diabetes and stroke, each standard
      deviation (SD) increase in dietary vitamin E intake was associated with a 14%
      reduced likelihood of prevalent hearing loss, odds ratio, OR, 0.86 (95%
      confidence interval, CI, 0.78-0.98). Those in the highest quintile of dietary
      vitamin A intake had a 47% reduced risk of having moderate or greater hearing
      loss (>40 dB HL) compared to those in the lowest quintile of intake,
      multivariable-adjusted OR 0.53 (CI 0.30-0.92), P for trend = 0.04. However,
      dietary antioxidant intake was not associated with the 5-year incidence of
      hearing loss. CONCLUSIONS: Dietary vitamin A and vitamin E intake were
      significantly associated with the prevalence of hearing loss. However, dietary
      antioxidant intake did not increase the risk of incident hearing loss. Further
      large, prospective studies are warranted to assess these relationships in older
      adults.

PMID- 22159781
TI  - Effects of a short-term personalized Intermittent Work Exercise Program (IWEP) on
      maximal cardio-respiratory function and endurance parameters among healthy young
      and older seniors.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficiency of a short-term
      Intermittent Work Exercise Program (IWEP) among healthy elderly subjects. STUDY
      DESIGN AND SETTING: This longitudinal prospective study took place at the
      Strasbourg University Hospital geriatric department. STUDY PARTICIPANTS: One
      hundred and fifty older volunteers, previously determined as being free from
      cardiac and pulmonary disease, were separated into two age groups: the "young
      senior" (60.2 +/- 3.1 yr) and the "older senior" groups (70.8 +/- 5.2 yr). These
      groups were then subdivided by gender into the "young female senior", "young male
      senior" "older female senior" and "older male senior" groups. INTERVENTION:
      Before and after the IWEP, all subjects were asked to perform an incremental
      cycle exercise to obtain their first ventilatory threshold (VT1), maximal
      tolerated power (MTP), peak oxygen uptake (VO2peak) and maximal minute
      ventilation (MMV). The IWEP consisted of a 30-min cycling exercise which took
      place twice a week, and was divided into six 5-min stages consisting of 4 min at
      VT1 intensity and 1 min at 90% MTP. MEASUREMENTS: An assessment was made of the
      effects of the IWEP on maximal cardio-respiratory function (MTP, VO2peak, MMV)
      and endurance parameters (VT1, heart rate [HR] measured at pretraining VT1 and
      lactate concentrations at pre-training MTP). RESULTS: This short-term training
      program resulted in a significant increase of MTP (from 13.2% to 20.6%), VO2peak
      (from 8.9% to 16.6%) and MMV (from 11.1% to 21.8%) in all groups (p<0.05). VT1
      improved from 21% at pretraining to 27%, while HR at pre-training VT1 as well as
      lactate concentrations at pre-training MTP decreased significantly in all groups
      (p<0.05). The post-training values for VO2peak and MMV of the "older seniors"
      were not significantly different (p>0.05) from the "young seniors" pre-training
      values for the same parameters. CONCLUSION: The most striking finding in this
      study is that after only 9 weeks, our short-term "individually-tailored" IWEP
      significantly improved both maximal cardio-respiratory function and endurance
      parameters in healthy, previously untrained seniors.

PMID- 22159780
TI  - Study of Mini-Mental State Exam evolution in community-dwelling subjects aged
      over 60 years without dementia.
AB  - OBJECTIVE: In recent years, the Mini-Mental State Examination (MMSE) has been
      widely used and has been proposed for cognitive decline screening in the
      framework of a systematic geriatric evaluation in health centers. The aim of the
      present longitudinal study was to identify the potential determinants of MMSE
      score and its evolution over a 4-year period in a population aged over sixty
      years with good general health without dementia and consulting for a health check
      up. DESIGN: Longitudinal study. SETTING: The preventive medical center (CMP) in
      Nancy. PARTICIPANTS: 687 subjects over 60 years of age (mean age 65.6 +/- 5.07
      years) were included from the Senior health examination study. MEASUREMENTS: All
      subjects underwent 2 visits over a period of 4 years. MMSE measurement and a self
      administered questionnaire of emotional and psychological state were evaluated at
      baseline and at the follow-up visit. RESULTS: The major components of total
      variance of baseline MMSE were represented by education level, practice of
      regular physical activity, nervousness and despair. Multivariate analysis
      identified 3 variables at baseline visit that independently predicted annual
      changes in MMSE: MMSE score, education level and "Difficulty in social relations"
      (r= -0.222, 0.154 and -0.255 respectively). CONCLUSIONS: Education level and
      several psychological factors may influence MMSE score and its evolution over
      time in community-dwelling subjects aged over 60 years without dementia. In these
      subjects, a low MMSE score does not predict cognitive decline over a period of 4
      years. Therefore, the reliability of MMSE in this type of population is
      questionable.

PMID- 22159782
TI  - Antioxidant micronutrients improve intrinsic and UV-induced apoptosis of human
      lymphocytes particularly in elderly people.
AB  - OBJECTIVE: Aging and oxidative stress may lead to enhanced cellular damage and
      programmed cell death. To study the association of intrinsic apoptosis with age
      and the effect of antioxidant supplementation on intrinsic and UV-induced
      apoptosis in children, young and elderly people. METHODS: The study was a 2
      months, double-blind, randomized trial. Three age groups were studied: children,
      young adults and elderly people. A total of 274 healthy subjects were allocated
      to a group supplemented with moderate amounts of retinol, beta-carotene, alpha
      tocopherol, ascorbic acid and selenium or placebo. Plasma oxidative stress
      parameters were detected and apoptosis of lymphocytes was evaluated with TUNEL
      staining. RESULTS: At baseline, percentages of intrinsic apoptosis were 13.8% and
      11.1% in elderly and young people, respectively, both significantly higher than
      children (6.3%). A decrease of 1.7% and 2.3% in intrinsic apoptosis of
      lymphocytes was found in the supplemented groups of young and elderly people
      compared with their control groups (all p values <0.001), but no significant
      decrease in children. Moreover, percentages UV-induced apoptosis significantly
      decreased by 1.4%, 1.9% and 3.1% in children, young and elderly people,
      respectively, compared with control groups after the trial. There were
      considerable increments in concentrations of plasma beta-carotene, retinol,
      tocopherol, ascorbic acid and selenium in all three treated groups after the
      supplementation. CONCLUSIONS: Young and elderly people have a higher intrinsic
      apoptosis than children, which was improved by antioxidant supplementation. UV
      induced damage was attenuated by the supplementation in all three age groups.

PMID- 22159783
TI  - A new hierarchical classification for prognosis of hip fracture after 2 years'
      follow-up.
AB  - OBJECTIVES: To examine the prognostic value of different profiles of hip fracture
      patients for recovery of pre-fracture functional level and for post-fracture
      mortality. DESIGN: Observational, longitudinal study. SETTING: University
      hospital. PARTICIPANTS: Five hundred and eight patients who received surgery for
      hip fracture and were followed for 24 months post-fracture. MEASUMENTS: Patients
      were assessed according to age, number of independent activities of daily living
      (ADLs) and dementia. The probability of recovery of previous ambulation level and
      mortality was established at 3, 6, 12 and 24 months post-fracture. Patients were
      first classified according to the seven different profiles previously established
      by Penrod. A new patient classification system was then created using different
      patient groups: persons aged 75 or older were first classified based on the
      number of independent ADLs they could perform (4, 3-2 and 1-0) and were then
      subdivided according to age (75-84 years and >84 years) and presence of dementia.
      RESULTS: Mean age was 84.5 (SD 6.3) years. Almost all (90.6%) patients walked
      independently before the fracture. At 24 months' follow-up, the probability of
      recovery to previous level of ambulation was 73.6%. The new classification into
      seven groups had higher prognostic value than Penrod's system. Patients under 75
      had 95.1% probability of functional recovery and 9.6% of dying. At the other
      extreme, those over 84 years with 0-1 independent activities of daily living and
      dementia had 23.9% probability of recovery and 71.4% of dying. CONCLUSION: Hip
      fracture patients can be classified into homogeneous groups with different
      prognostic profiles based on pre-fracture characteristics. This new
      classification improves Penrod's previous system by establishing groups of
      patients hierarchically ordered by the probability of recovery and mortality at
      3, 6, 12 and 24 months post-fracture.

PMID- 22159784
TI  - Direct relationship of body mass index and waist circumference with body tissue
      distribution in elderly persons.
AB  - OBJECTIVES: To explore the relationship of BMI and WC with muscle/adipose tissue
      mass ratios and with trunk adipose tissue distribution, based on an anatomical 5
      compartment model, by dissection of cadavers of elderly persons. DESIGN: Cross
      sectional explorative study. SETTING: Brussels Cadaver Analysis Study.
      PARTICIPANTS: Cadavers of twenty-nine white Caucasian elderly persons (17 females
      and 12 males, aged 78.1+/-6.9 years). MEASUREMENTS: Whole body and trunk
      composition were determined at the anatomical tissue-system level by direct
      dissection. RESULTS: BMI and WC were significantly and positively related to
      absolute tissue masses in both sexes. Muscle tissue mass, adipose tissue mass and
      trunk internal adipose tissue mass correlated better with BMI (r-values between
      0.68 and 0.89) than with WC (r-values between 0.49 and 0.71). BMI was
      significantly and inversely related with various muscle/adipose tissue ratios in
      both sexes (r-values between -0.54 and -0.68). WC correlated with muscle/adipose
      tissue ratios in females only (r-values between -0.55 and -0.64). BMI was also
      significantly related to trunk adipose tissue distribution in elderly females,
      but not in males. When comparing individual tissue proportions within and between
      adjacent BMI-classifications or WC categories, body composition varied
      considerably. CONCLUSION: Our results show that BMI and WC are significantly
      related with adipose tissue mass and with several ratios of muscle to adipose
      tissue in elderly subjects. However, cautious clinical interpretation is
      warranted since important differences in tissue mass proportions were found in
      subjects with similar BMI and/or WC values.

PMID- 22159785
TI  - Timed Up and Go test and risk of falls in older adults: a systematic review.
AB  - OBJECTIVE: To assess the association and the predictive ability of the Timed Up
      and Go test (TUG) on the occurrence of falls among people aged 65 and older.
      METHODS: A systematic English Medline literature search was conducted on November
      30, 2009 with no limit of date using the following Medical Subject Heading (MeSH)
      terms "Aged OR aged, 80 and over" AND "Accidental falls" combined with the terms
      "Timed Up and Go" OR "Get Up and Go". The search also included the Cochrane
      library and the reference lists of the retrieved articles. RESULTS: Of the 92
      selected studies, 11 met the selection criteria and were included in the final
      analysis. Fall rate ranged from 7.5 to 60.0% in the selected studies. The cut-off
      time separating non-fallers and fallers varied from 10 to 32.6 seconds. All
      retrospective studies showed a significant positive association between the time
      taken to perform the TUG and a history of falls with the highest odds ratio (OR)
      calculated at 42.3 [5.1 - 346.9]. In contrast, only one prospective study found a
      significant association with the occurrence of future falls. This association
      with incident falls was lower than in retrospective studies. CONCLUSIONS:
      Although retrospective studies found that the TUG time performance is associated
      with a past history of falls, its predictive ability for future falls remains
      limited. In addition, standardization of testing conditions combined with a
      control of the significant potential confounders (age, female gender and
      comorbidities) would provide better information about the TUG predictive value
      for future falls in older adults.

PMID- 22159786
TI  - Bone quantitative ultrasound measurements in relation to the metabolic syndrome
      and type 2 diabetes mellitus in a cohort of elderly subjects at high risk of
      cardiovascular disease from the PREDIMED study.
AB  - OBJECTIVE: The aim of this study is to determine whether metabolic syndrome, its
      individual components, or the presence of type 2 diabetes mellitus are associated
      with a better bone status estimated by quantitative ultrasound at the calcaneus.
      DESIGN: Cross-sectional study. SETTING: Outpatient clinics. PARTICIPANTS: 251
      elderly subjects at high cardiovascular risk from the PREDIMED study were
      included. MEASUREMENTS: MetS was defined according to the ATPIII diagnosis
      criteria. Calcaneus quantitative ultrasound (QUS) assessment was performed using
      the Sahara system. RESULTS: Subjects with MetS showed significantly lower 24-hour
      urinary deoxypyridinoline/creatinine (u-DPD/creatinine) levels and higher
      broadband ultrasound attenuation, and a tendency to higher bone mineral density
      (BMD) and quantitative ultrasound index (QUI) than their counterparts.
      Individuals with type 2 diabetes mellitus (T2DM) showed a significantly higher
      bone broadband ultrasound attenuation (BUA) and QUI than their non-diabetic
      counterparts, despite they shown a higher prevalence of osteoporotic fractures.
      Multiple linear regression analyses showed that quantitative ultrasound
      parameters were positively associated with the metabolic syndrome and T2DM. Of
      the bone biochemical markers, only u-DPD/creatinine was related to MetS,
      abdominal obesity, hypertriglyceridemia component of the MetS, and the number of
      features that define the MetS. CONCLUSION: This is the first study showing a
      positive association between MetS or T2DM with better bone status and lower bone
      resorption markers measured by quantitative ultrasound. Our results suggest that
      metabolic abnormalities have a positive effect on healthy bone in elderly
      subjects at high risk of cardiovascular disease.

PMID- 22159787
TI  - The role of entropy in initializing the aggregation of peptides: a first
      principle study on oligopeptide oligomerization.
AB  - The initiation and progression of Alzheimer's disease is coupled to the oligo-
      and polymerization of amyloid peptides in the brain. Amyloid like aggregates of
      protein domains were found practically independent of their primary sequences.
      Thus, the driving force of the transformation from the original to a disordered
      amyloid fold is expected to lie in the protein backbone common to all proteins.
      In order to investigate the thermodynamics of oligomerization, full geometry
      optimizations and frequency calculations were performed both on parallel and
      antiparallel beta-pleated sheet model structures of [HCO-(Ala)(1-6)-NH(2)](2) and
      (For-Ala(1-2)-NH(2))(1-6) peptides, both at the B3LYP and M05-2X/6
      311++G(d,p)//M05-2X/6-31G(d) levels of theory, both in vacuum and in water. Our
      results show that relative entropy and enthalpy both show a hyperbolic decrease
      with increasing residue number and with increasing number of strands as well.
      Thus, di- and oligomerization are always thermodynamically favored. Antiparallel
      arrangements were found to have greater stability than parallel arrangements of
      the polypeptide backbones. During our study the relative changes in thermodynamic
      functions are found to be constant for long enough peptides, indicating that
      stability and entropy terms are predictable. All thermodynamic functions of
      antiparallel di- and oligomers show a staggered nature along the increasing
      residue number. By identifying and analyzing the 6 newly emerging dimer
      vibrational modes of the 10- and 14-membered building units, the staggered nature
      of the entropy function can be rationalized. Thus, the vanishing rotational and
      translational modes with respect to single strands are converted into entropy
      terms "holding tight" the dimers and oligomers formed, rationalizing the
      intrinsic adherence of natural polypeptide backbones to aggregate.

PMID- 22159789
TI  - Mathematical ecology: why mechanistic models?

PMID- 22159788
TI  - Evaluation of methylation status of the eNOS promoter at birth in relation to
      childhood bone mineral content.
AB  - Our previous work has shown associations between childhood adiposity and
      perinatal methylation status of several genes in umbilical cord tissue, including
      endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS
      is important in bone metabolism; we therefore related the methylation status of
      the eNOS gene promoter in stored umbilical cord to childhood bone size and
      density in a group of 9-year-old children. We used Sequenom MassARRAY to assess
      the methylation status of two CpGs in the eNOS promoter, identified from our
      previous study, in stored umbilical cords of 66 children who formed part of a
      Southampton birth cohort and who had measurements of bone size and density at age
      9 years (Lunar DPXL DXA instrument). Percentage methylation varied greatly
      between subjects. For one of the two CpGs, eNOS chr7:150315553 + , after taking
      account of age and sex, there were strong positive associations between
      methylation status and the child's whole-body bone area (r = 0.28, P = 0.02),
      bone mineral content (r = 0.34, P = 0.005), and areal bone mineral density (r =
      0.34, P = 0.005) at age 9 years. These associations were independent of
      previously documented maternal determinants of offspring bone mass. Our findings
      suggest an association between methylation status at birth of a specific CpG
      within the eNOS promoter and bone mineral content in childhood. This supports a
      role for eNOS in bone growth and metabolism and implies that its contribution may
      at least in part occur during early skeletal development.

PMID- 22159811
TI  - Actinomycosis of the nasopharynx causing carotid occlusion.

PMID- 22159812
TI  - Testing the role of patch openness as a causal mechanism for apparent area
      sensitivity in a grassland specialist.
AB  - Area sensitivity, species being disproportionately present on larger habitat
      patches, has been identified in many taxa. We propose that some apparently area
      sensitive species are actually responding to how open a habitat patch is, rather
      than to patch size. We tested this hypothesis for Bobolinks (Dolichonyx
      oryzivorus) by comparing density and occupancy to a novel openness index, patch
      area, and edge effects. Bobolink density and occupancy showed significant
      relationships with openness, but logistic models based on an openness occupancy
      threshold had greater explanatory power. Thresholds remained approximately
      consistent from June through August, and shifted to be more open in September.
      Variance partitioning supported the openness index as unique and relevant. We
      found no relationships between measures of body condition (body mass, body size,
      circulating corticosterone levels) and either openness or area. Our findings have
      implications for studies of area sensitivity, especially with regards to
      inconsistencies reported within species: specifically, (1) whether or not a study
      finds a species to be area sensitive may depend on whether small, open sites were
      sampled, and (2) area regressions were sensitive to observed densities at the
      largest sites, suggesting that variation in these fields could lead to
      inconsistent area sensitivity responses. Responses to openness may be a
      consequence of habitat selection mediated by predator effects. Finally, openness
      measures may have applications for predicting effects of habitat management or
      development, such as adding wind turbines, in open habitat.

PMID- 22159813
TI  - The predictability of traits and ecological interactions on 17 different crosses
      of hybrid oaks.
AB  - Herbivory on hybrid plants has the potential to affect patterns of plant
      evolution, such as limiting gene-flow through hybrids, and can also affect
      herbivore biodiversity. However, few studies have surveyed multiple hybrid
      species to identify phylogenetic patterns in the inheritance of plant traits that
      may drive herbivory. We surveyed 15 leaf traits and patterns of chewing, mining,
      and galling herbivory in a common garden of 17 artificially crossed hybrid oak
      species and each of their parental species over a 2-year period. Using a
      phylogeny of oaks, we tested whether hybrids that resulted from more divergent
      parents received more herbivory than those derived from closely related parents
      (as would be predicted by a build-up of incompatibilities in defensive systems
      over evolutionary time) and found only marginal evidence in support of this. We
      found that chewing damage to hybrids was weakly predicted by the relatedness of a
      parental species to the single native oak. The levels of chewing and mining
      herbivory on hybrids were typically intermediate to those of their parental
      species, though less than the parental mean for chewing damage in 2008. Most leaf
      traits of hybrids were also intermediate to those of their parental species.
      There was no clear pattern in terms of an association between 11 species of
      cynipid gall wasps and hybrids. The patterns of (1) intermediate levels of
      herbivory on hybrids and (2) no trend in herbivory on hybrids based on the
      phylogenetic relatedness of parental species suggest that herbivory may not play
      a general role in limiting hybrid fitness (and thus gene-flow through hybrids) in
      oaks.

PMID- 22159815
TI  - Mild renal disease increases major bleeding in patients with atrial fibrillation
      undergoing percutaneous coronary stenting. ...or why clinical cardiologists and
      interventionalists should be friends.

PMID- 22159814
TI  - NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in
      human gastric cancer cells harboring KRAS mutations.
AB  - Aberrations of Phosphoinositide 3-kinase (PI3K)/AKT signaling are frequently
      observed in many types of cancer, promoting its emergence as a promising target
      for cancer treatment. PI3K can become activated by various pathways, one of which
      includes RAS. RAS can not only directly activate the PI3K/AKT pathway via binding
      to p110 of PI3K, but also regulates mTOR via ERK or RSK independently of the
      PI3K/AKT pathway. Thus, actively mutated RAS can constitutively activate PI3K
      signaling. Additionally, in RAS tumorigenic transformation, signal transducer and
      activator of transcription 3 (STAT3) has been known also to be required. In this
      study, we examined the efficacy of NVP-BKM120, a pan-class I PI3K inhibitor in
      human gastric cancer cells and hypothesized that the combined inhibition of PI3K
      and STAT3 would be synergistic in KRAS mutant gastric cancer cells. NVP-BKM120
      demonstrated anti-proliferative activity in 11 human gastric cancer cell lines by
      decreasing mTOR downstream signaling. But NVP-BKM120 treatment increased p-AKT by
      subsequent abrogation of feedback inhibition by stabilizing insulin receptor
      substrate-1. In KRAS mutant gastric cancer cells, either p-ERK or p-STAT3 was
      also increased upon treatment of NVP-BKM120. The synergistic efficacy study
      demonstrated that dual PI3K and STAT3 blockade showed a synergism in cells
      harboring mutated KRAS by inducing apoptosis. The synergistic effect was not seen
      in KRAS wild-type cells. Together, these findings suggest for the first time that
      the dual inhibition of PI3K and STAT3 signaling may be an effective therapeutic
      strategy for KRAS mutant gastric cancer patients.

PMID- 22159816
TI  - Alpinetin suppresses proliferation of human hepatoma cells by the activation of
      MKK7 and elevates sensitization to cis-diammined dichloridoplatium.
AB  - Alpinetin is a type of novel plant flavonoid derived from Alpinia katsumadai
      Hayata, found to possess strong anti-hepatoma effects. However, the detailed
      antitumor mechanism of alpinetin remains unclear. Mitogen-activated protein
      kinase kinase-7 (MKK7) can regulate cellular growth, differentiation and
      apoptosis. The aim of this study was to investigate the role of MKK7 in the anti
      hepatoma effect mediated by alpinetin. HepG2 cells were treated with alpinetin at
      various doses and for different times, and the levels of phosphorylated MKK7 (p
      MKK7) and total MKK7 were tested by RT-PCR and western blotting. Following
      transient transfection with RNA interference, cell viability and cell cycle stage
      were determined using methyl thiazolyl tetrazolium assay and flow cytometry, in
      order to assess the antitumor action of alpinetin. In addition,
      chemosensitization to cis-diammined dichloridoplatium (CDDP) by alpinetin was
      assessed by cell counting array and the cell growth inhibitory rate was
      calculated. The results showed that alpinetin suppressed HepG2 cell proliferation
      and arrested cells in the G0/G1 phase by up-regulating the expression levels of p
      MKK7. On the contrary, inhibiting the expression of MKK7 reversed the antitumor
      effect of alpinetin. Moreover, alpinetin enhanced the sensitivity of HepG2
      hepatoma cells to the chemotherapeutic agent CDDP. Taken together, our studies
      indicate that activation of MKK7 mediates the anti-hepatoma effect of alpinetin.
      MKK7 may be a putative target for molecular therapy against hepatoma and
      alpinetin could serve as a potential agent for the development of hepatoma
      therapy.

PMID- 22159817
TI  - Novel mutations of MVK gene in Japanese family members affected with
      hyperimmunoglobulinemia D and periodic fever syndrome.
AB  - Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) is a recessively
      inherited recurrent fever syndrome. We describe a family of eldest son and
      monozygotic twin younger sisters with characteristic syndrome of HIDS, but normal
      level of IgD. Mevalonate kinase (MK) activity was deficient in all of them, and
      analysis of the MVK gene revealed compound heterozygosity for 2 new mutations,
      one of which was the disease-causing splicing mutation and the other was a novel
      missense mutation. All the patients had the same compound heterozygous mutations
      c.227-1 G > A and c.833 T > C, which resulted in exon 4 skipping and p.Val278Ala.
      This is the first case in which exon skipping mutation of the MVK gene has been
      certainly identified at the genomic DNA level. In each case, in which HIDS is
      clinically suspected, despite normal IgD level, analysis of MK activity and the
      MVK gene should be performed.

PMID- 22159818
TI  - Spinal inflammation by magnetic resonance imaging in patients with ankylosing
      spondylitis: association with disease activity and outcome parameters.
AB  - Magnetic resonance imaging (MRI) has major contribution in early diagnosis of
      ankylosing spondylitis (AS). As it is difficult to determine disease activity
      owing to the lack of close relation between laboratory tests, clinical findings
      and imaging, MRI has been used as an objective outcome measure. The aim of this
      study is to investigate the relation between spinal MRI findings with disease
      activity and other outcome measures. Fifty patients fulfilling modified New York
      criteria for AS were enrolled to the study. All the patients were evaluated with
      Bath AS Disease Activity Index (BASDAI), AS Disease Activity Score (ASDAS), Bath
      AS Functional Index (BASFI), Bath AS Metrology Index (BASMI), Bath AS Radiology
      Index (BASRI) and As Quality of Life. Erythrocyte sedimentation rate (ESR) and C
      reactive protein (CRP) were measured as laboratory parameters, and ASspiMR scores
      were determined by spinal MRI. The median total ASspiMR-a score was 5.2. Spinal
      inflammation was evaluated in spinal segments, and thoracic segments had the
      highest mean ASspiMR-a level (3.1 +/- 5.94). Cervical and lumbar ASspiMR were
      correlated with only BASRI, and total ASspiMR score was correlated with BASRI,
      BASMI and CRP. Thoracic ASspiMR score was correlated with patient's and doctor's
      global assessments, BASFI, BASMI, BASRI, ASDAS A, ASDAS B, ASDAS C, ASDAS D, ESR
      and CRP (P < 0.05). According to our results, the thoracic spine was the most
      related region with disease activity parameters and clinical outcome measures, so
      we suggest thoracic spine MRI evaluation in order to determine the disease
      activity.

PMID- 22159820
TI  - Resistive vibration exercise retards bone loss in weight-bearing skeletons during
      60 days bed rest.
AB  - Countermeasures are desirable to retard bone loss during long-term space flight.
      We evaluated the effect of an intervention protocol on bed rest-induced bone
      loss. INTRODUCTION: We developed a resistive vibration exercise (RVE) platform to
      test if an intervention RVE protocol would be effective to protect bed rest
      induced bone loss. METHODS: Fourteen male subjects were assigned randomly to
      either the RVE group (n = 7) that performed daily supervised resistive vibration
      exercise or to the no any exercise control (CON) group (n = 7). Both dual-energy
      X-ray absorptiometry and peripheral quantitative computed tomography were used to
      monitor changes in bone mineral density. RESULTS: RVE significantly prevented
      bone loss at multiple skeletal sites, including calcaneus, distal tibia, hip, and
      lumbar spine (L2-L4). The ratio of urinary calcium and creatinine was found
      higher after starting bed rest in CON group while no significant changes were
      observed in RVE group. No significant temporal change was found for osteocalcin-N
      during and after bed rest in CON group. However, a significant increase was shown
      after bed rest in RVE group. In both groups, the urinary concentration of bone
      resorption markers, such as C-telopeptide of type I collagen (CTX-I) and
      deoxypyridinoline (DPD), were significantly elevated after bed rest. In the CON
      group, no significant temporal effect was found for hydroxyproline (HOP), CTX-I,
      and DPD during bed rest and the serum concentration of HOP and TGF-beta
      significantly increased about 52.04% and 24.03%, respectively only after bed
      rest. However, all these markers tended to decrease in the RVE group.
      CONCLUSIONS: Our results might imply that the intervention of RVE retarded bone
      loss induced by simulated microgravity in humans that was mainly attributed to
      its anabolic effects.

PMID- 22159821
TI  - A follow-up association study of two genetic variants for bone mineral density
      variation in Caucasians.
AB  - SUMMARY: We tested whether two genetic variants were associated with BMD at
      multiple clinically relevant skeletal sites in Caucasians. We found that variant
      rs7776725 is consistently associated with hip, spine, wrist and whole-body BMD,
      which highlights the potential importance of this variant or linked variants for
      osteoporosis. INTRODUCTION: A recent genome-wide association study identified two
      single nucleotide polymorphisms (SNPs), rs7776725 and rs1721400, that were
      associated with bone mineral density (BMD) variation at the radius, tibia and
      calcaneus in a Korean population. In this study, we aimed to test whether the
      association of these two genetic variants can be replicated in Caucasians and
      whether their association with BMD can be extended to other clinically relevant
      skeletal sites. METHODS: We performed this study in two large cohorts of
      unrelated US Caucasians. Area BMD at the hip, spine, wrist (ultra-distal radius)
      and whole body were measured with Hologic dual-energy X-ray absorptiometer. SNPs
      were genotyped with Affymetrix human genome-wide genotyping arrays. Association
      analyses were performed using PLINK. RESULTS: We detected highly significant
      association (combined p = 1.42 * 10(-16)) of rs7776725 with wrist BMD but only
      borderline association signal (combined p = 0.017) for rs1721400 with wrist BMD.
      In addition, we found that rs7776725 was associated with BMD at the hip, spine
      and whole body. At the FAM3C gene locus where rs7776725 was located, we
      identified several other SNPs (rs4727922, rs1803389, rs718766 and rs7793554) that
      were also associated with BMD. CONCLUSIONS: This is the first follow-up
      association study of rs7776725 and rs1721400 with BMD. The rs7776725 showed
      consistent association with BMD at multiple clinically important skeletal sites,
      which highlighted the potential importance of rs7776725 or linked SNPs for risk
      of osteoporosis. Further in-depth re-sequencing studies and functional assays are
      necessary to elucidate the underlying mechanisms.

PMID- 22159822
TI  - Longitudinal assessment of in vivo bone dynamics in a mouse tail model of
      postmenopausal osteoporosis.
AB  - Recently, it has been shown that transient bone biology can be observed in vivo
      using time-lapse micro-computed tomography (MUCT) in the mouse tail bone.
      Nevertheless, in order for the mouse tail bone to be a model for human disease,
      the hallmarks of any disease must be mimicked. The aim of this study was to
      investigate whether postmenopausal osteoporosis could be modeled in caudal
      vertebrae of C57Bl/6 mice, considering static and dynamic bone morphometry as
      well as mechanical properties, and to describe temporal changes in bone
      remodeling rates. Twenty C57Bl/6 mice were ovariectomized (OVX, n = 11) or sham
      operated (SHM, n = 9) and monitored with in vivo MUCT on the day of surgery and
      every 2 weeks after, up to 12 weeks. There was a significant decrease in bone
      volume fraction for OVX (-35%) compared to SHM (+16%) in trabecular bone (P <
      0.001). For OVX, high-turnover bone loss was observed, with the bone resorption
      rate exceeding the bone formation rate (P < 0.001). Furthermore there was a
      significant decrease in whole-bone stiffness for OVX (-16%) compared to SHM
      (+11%, P < 0.001). From these results we conclude that the mouse tail vertebra
      mimics postmenopausal bone loss with respect to these parameters and therefore
      might be a suitable model for postmenopausal osteoporosis. When evaluating
      temporal changes in remodeling rates, we found that OVX caused an immediate
      increase in bone resorption rate (P < 0.001) and a delayed increase in bone
      formation rate (P < 0.001). Monitoring transient bone biology is a promising
      method for future research.

PMID- 22159823
TI  - Clinical impact of right accessory hepatic artery injury in deceased donor
      livers.
AB  - BACKGROUND: Right accessory hepatic artery (RAHA) injury at retrieval is a rare
      complication of deceased liver procurement. Arterial reconstruction is often
      required under these circumstances which could potentially increase the risk of
      hepatic artery thrombosis (HAT). The aim of this study is to investigate whether
      RAHA injury affects the incidence of HAT, early biliary complications, or 3-month
      graft and patient survival rates. METHODS: All adult liver transplants performed
      between 1994 and February 2007 at Addenbrooke's Hospital, Cambridge, UK were
      considered for inclusion in the study. Grafts were divided into three groups
      depending on the presence of RAHA and injury (Group 1: normal anatomy and single
      hepatic artery anastomosis; Group 2: RAHA requiring reconstruction; Group 3: RAHA
      injury requiring reconstruction). RESULTS: Eight hundred and forty-four liver
      transplants were included in the study (Group 1: 654 grafts; Group 2: 63 grafts;
      Group 3: 14 grafts). The incidence of HAT (Group 1, 2.9%; Group 2, 6.4%; Group 3,
      14.3%) was significantly different between the three groups (P = 0.01); biliary
      complications at 3 months (Group 1, 7.1%; Group 2, 11.1%; Group 3, 7.1%) were not
      significantly different. Graft and patient survival at 3 months were
      significantly worse in Group 3 when compared with Group 2 (61.5 vs. 88.3%, P =
      0.01; 81.8 vs. 98.2%, P = 0.02). CONCLUSION: This is the first study analysing
      the clinical impact of RAHA injury during liver procurement. We conclude that the
      use of liver grafts with RAHA injury does result in a higher HAT rate and is also
      associated with lower graft and patient survival rates at 3 months.

PMID- 22159824
TI  - Reappraisal of percutaneous transhepatic biliary drainage tract recurrence after
      resection of perihilar bile duct cancer.
AB  - BACKGROUND: The high incidence of percutaneous transhepatic biliary drainage
      (PTBD) tract recurrence after resection of perihilar bile duct cancer (BDC) at a
      reference single center has suggested the need for endoscopic biliary drainage
      (EBD) to prevent PTBD-related tumor recurrence. To determine the general
      applicability of these findings, we validated the risk of PTBD tract recurrence
      in patients with resected BDC in our high-volume center. METHODS: The medical
      records of 306 patients with perihilar BDC who underwent hepatobiliary resection
      with curative intent over 10 years were reviewed retrospectively. RESULTS: Of the
      306 patients, 293 (95.8%) underwent biliary decompression, 171 (56.1%) by
      preoperative PTBD, 62 (20.3%) by EBD alone, and 60 (19.7%) by both. Of the 231
      patients who underwent PTBD, 160 (69.3%), 62 (26.8%), and 9 (3.9%) had one, two,
      or three catheters, respectively (mean of 1.3 catheters per patient for a median
      23 days). No patient experienced synchronous PTBD tract metastasis, whereas 4
      (1.7%) experienced PTBD tract recurrence a median 13.5 months after surgery, with
      3 of these patients having an intraabdominal recurrence soon afterward. Only one
      patient had a solitary tract recurrence without intraabdominal metastasis. These
      patients survived for a median 25 months, which is comparable to survival
      outcomes after noncurative resection. No risk factor was significantly associated
      with PTBD tract recurrence. CONCLUSIONS: We think that the risk of PTBD tract
      recurrence after resection of perihilar BDC is not negligible but is much lower
      than previously reported. There is no definitive reason to avoid PTBD when it is
      indicated.

PMID- 22159826
TI  - Spatiotemporal mapping of visual attention.
AB  - The spatial distribution and the temporal dynamics of attention are well
      understood in isolation, but their interaction remains an open question. How does
      the shape of the attentional focus evolve over time? To answer this question, we
      measured spatiotemporal maps of endogenous and exogenous attention in humans
      (more than 140,000 trials in 23 subjects). We tested the visibility of a low
      contrast target presented (50 ms) at different spatial distances and temporal
      delays from a cue in a noisy background. The cue was a non-informative salient
      peripheral (5 degrees ) stimulus for exogenous attention and a central arrow cue
      (valid 66.6%) pointing left or right for endogenous attention. As a measure of
      attention, we determined, for each distance and delay, the background contrast
      compensation required to keep performance at 75%. The spatiotemporal mapping of
      exogenous attention revealed a significant enhancement zone from 150 to 430 ms,
      extending up to 6 degrees  from the cue. Endogenous attention maps showed a peak
      at the cued side at 400 ms and between 8 and 10 degrees  from the cue. Modeling
      suggests that the data are compatible with a constant spotlight shape across
      time. Our results represent the first detailed spatiotemporal maps of both
      endogenous and exogenous attention.

PMID- 22159825
TI  - Identification and characterization of a novel powdery mildew resistance gene
      PmG3M derived from wild emmer wheat, Triticum dicoccoides.
AB  - Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt) is one of the
      most important wheat diseases worldwide. Wild emmer wheat, Triticum turgidum ssp.
      dicoccoides, the tetraploid ancestor (AABB) of domesticated bread and durum
      wheat, harbors many important alleles for resistance to various diseases,
      including powdery mildew. In the current study, two tetraploid wheat mapping
      populations, derived from a cross between durum wheat (cv. Langdon) and wild
      emmer wheat (accession G-305-3M), were used to identify and map a novel powdery
      mildew resistance gene. Wild emmer accession G-305-3M was resistant to all 47 Bgt
      isolates tested, from Israel and Switzerland. Segregation ratios of F(2)
      progenies and F(6) recombinant inbred line (RIL) mapping populations, in their
      reactions to inoculation with Bgt, revealed a Mendelian pattern (3:1 and 1:1,
      respectively), indicating the role of a single dominant gene derived from T.
      dicoccoides accession G-305-3M. This gene, temporarily designated PmG3M, was
      mapped on chromosome 6BL and physically assigned to chromosome deletion bin 6BL
      0.70-1.00. The F(2) mapping population was used to construct a genetic map of the
      PmG3M gene region consisted of six simple sequence repeats (SSR), 11 resistance
      gene analog (RGA), and two target region amplification polymorphism (TRAP)
      markers. A second map, constructed based on the F(6) RIL population, using a set
      of skeleton SSR markers, confirmed the order of loci and distances obtained for
      the F(2) population. The discovery and mapping of this novel powdery mildew
      resistance gene emphasize the importance of the wild emmer wheat gene pool as a
      source for crop improvement.

PMID- 22159827
TI  - Previous cesarean section, gestational age at first delivery and subsequent risk
      of pre-eclampsia in obese mothers.
AB  - PURPOSE: We examine the association between prior C-section and subsequent pre
      eclampsia; and describe the effect of gestational age at prior C-section, and
      obesity status on this association. METHODS: The study population included women
      with two subsequent singleton births in Missouri between 1998 and 2005. The risk
      for pre-eclampsia/eclampsia was assessed among women with and without prior
      cesarean delivery. The two groups were followed to their second pregnancy and the
      occurrence of pre-eclampsia was documented. Additionally, the history of pre
      eclampsia, prior cesarean at preterm, and obesity status were examined for their
      differential effects on the risk of pre-eclamsia. RESULTS: Women with prior C
      section were 28% more likely to have pre-eclampsia in their subsequent pregnancy
      [OR = 1.28; 95% CI = 1.20-1.37]. However, this result was not significant when
      women with pre-eclampsia in their first pregnancy were excluded. After this
      exclusion, a more than threefold increased risk for subsequent pre-eclampsia was
      observed in women with prior early C-section [OR = 3.15; 95% CI= 2.43-4.08],
      while the level of risk did not change in the prior late C-section group [OR =
      0.90; 95% CI= 0.82-1.00]. Subgroup analysis suggested that obesity status
      modified the risk of prior early C-section but did not affect the risk for prior
      late C-section. CONCLUSION: Preterm C-section in the first pregnancy may be
      associated with subsequent pre-eclampsia regardless of prior pre-eclampsia
      status.

PMID- 22159828
TI  - [Geriatric traumatology--new treatments, new opportunities].

PMID- 22159829
TI  - The Tyrolean Geriatric Fracture Center: an orthogeriatric co-management model.
AB  - BACKGROUND: The aging population is growing rapidly and this change results in an
      increase in the number of fragility fracture patients. Several reports describe
      their poor outcome. Integrated models of care have been published in order to
      improve quality of patient care. We established an orthogeriatric model of care
      at the Department of Trauma Surgery in Innsbruck in cooperation with the
      Department of Geriatric Medicine (Hochzirl) and the Department for
      Anesthesiology. This report describes our concept as well as initial experience.
      PATIENTS AND METHODS: We included all geriatric patients according to the
      definition of the German Geriatric Society. In all patients, basic demographic
      data, Charlson Comorbidity Index, and type of fracture were recorded. Main
      principles of the newly implemented system are the integration of a geriatrician
      in our team of trauma surgeons and anesthesiologists, prioritization of patients,
      development of our own clinical treatment guidelines, regular interdisciplinary
      and interprofessional meetings, a special outpatient clinic for these patients,
      and the better cooperation with the nearby Department of Geriatric Medicine.
      RESULTS: A total of 529 patients met our inclusion criteria during 2010; 77.4%
      were female and the mean age was 84.1 years. The overall medical complication
      rate was 20.4%. Of the patients, 36.1% had hip fractures and 70.5% could be
      operated mainly using spinal anesthesia within 24 h and their mean length of stay
      was significantly shorter than operations performed 5 years previously. At 3
      months, 86.7% of the patients had returned home and, thus, had reached their
      prefracture residency. CONCLUSION: A coordinated, multidisciplinary model for the
      treatment of fragility fractures has the potential to improve the quality of
      patient care. Several international studies report superior outcome and our own
      findings are promising as well. We could show that our major goals, e.g.,
      reduction of complications, shortening the length of stay, and restoration of the
      prefracture residency, can be improved by implementing such a model.

PMID- 22159830
TI  - "N-active": a new comanaged, orthogeriatric ward: observations and prospects.
AB  - The incidence of hip fractures increases with increasing age. Besides the actual
      trauma, it is mainly the comorbidities and an increased postoperative
      complication rate in old patients that lead to increased mortality in this
      patient population. Around 25% of patients who had previously been living
      independently continue to need long-term care after a hip fracture. Given this
      situation, the comanaged orthogeriatric unit "N-active" was opened at the
      Nuremberg Hospital in December 2010. The following article describes
      implementation of the ward and preliminary data. These show a positive impact of
      comanagement in terms of patient outcome, staff satisfaction, and also financial
      aspects.

PMID- 22159831
TI  - Risk assessment after hip fracture: check the "healthy" leg!
AB  - BACKGROUND AND AIM: Functional deficits may increase the risk for further falls
      after hip fracture. The aim of this study was to elucidate function and range of
      movement (ROM)-related risk factors. METHODS: The consecutive, prospective study
      included all patients admitted to the rehabilitation unit. The geriatric
      assessment was performed after admission and before discharge; ROM was measured
      using the neutral zero method. Falls, defined as unintentionally coming to rest
      on the floor, were documented. Patients' functions were analyzed comparing
      fallers to nonfallers. RESULTS: A total of 1,497 patients with a mean age of 81.1
      +/- 8.2 years were included. The incidence of falls during rehabilitation was 9.6
      per 1,000 patient-days and was related to patients' age: patients younger than 75
      years had an incidence of falls of 5.0, those between 75-84 years had an
      incidence of 9.5, and those >84 years had an incidence of 12.0, respectively.
      Fallers showed significantly more functional deficits both in the operated and on
      the nonoperated leg. Using logistic regression models, especially ROM measured in
      the frontal plane (hip adduction and abduction) of the nonoperated hip was
      significantly associated with an increased risk of falling (OR 0.986, 95% CI
      0.973-0.999, p = 0.037). CONCLUSION: Patients are at high risk for falls after
      hip fracture, with age itself being one of the most dominant risk factors. In
      addition to previously identified gait and mobility disorders, the physical
      limitations of arthritis of the "healthy" hip seem to be responsible for the
      functional decline. Therefore, it would be of interest to include the examination
      of the hips into a falls risk assessment battery.

PMID- 22159832
TI  - Treatment of osteoporosis in postmenopausal hip fracture patients after geriatric
      rehabilitation: changes over the last decade.
AB  - BACKGROUND: Osteoporotic hip fractures are a major cause of morbidity and
      mortality in postmenopausal women, and their impacts on society are substantial.
      Although adequate osteoporotic treatment reduces the risk of subsequent fractures
      and also mortality, only a minor proportion of the patients receives sufficient
      therapy. OBJECTIVES: The goal of the present study was to evaluate osteoporosis
      treatment in two different cohorts and to describe the changes after the
      implementation of a Geriatric Facture Center (GFC) in cooperation with a level 1
      trauma center. STUDY DESIGN: A retrospective, single-center cross sectional study
      design was used. METHODS: A total of 455 patients (70 years and older) were
      included at our department of geriatric medicine. The patients were split into
      two groups. The usual care (UC) group consisted of 327 patients admitted to our
      department from 2001-2004. The GFC group included 128 patients admitted from 2009
      2010. In addition to recording osteoporosis therapy, we collected demographic
      data, comorbidities, and different functional parameters of the patients. The
      data were collected retrospectively using medical records. SPSS 18.0 was used for
      statistical analysis. RESULTS: Of the patients, 43% in the GFC group received a
      specific antiresorptive or anabolic treatment (SAAT). Basic treatment with
      calcium and vitamin D3 was prescribed in 88% of the patients. The diagnosis
      "osteoporosis" was found in 73.4% of the discharge letters. In the UC group, the
      percentage of patients with a SAAT was 14.7%, calcium and vitamin D3 was
      prescribed in 30%, and the diagnosis was documented in 24.5%. All these
      differences are statistically significant (p < 0.0001). In the GFC group, better
      functional status and cognition were significantly associated with a higher rate
      of a prescribed SAAT, whereas age and comorbidities showed a negative
      association. CONCLUSION: Our results show that the management of osteoporosis in
      postmenopausal hip fracture patients has significantly improved over the last
      decade. From our point of view, the main impact on this development is due to the
      implementation of a GFC with corresponding guidelines and treatment steps. In
      addition to structural changes, the improved evidence for osteoporosis treatment,
      especially of geriatric patients, has a positive influence on osteoporosis
      therapy.

PMID- 22159833
TI  - Robotic-assisted rehabilitation of proximal humerus fractures in virtual
      environments: a pilot study.
AB  - BACKGROUND AND OBJECTIVE: With the growing incidence of upper arm fractures among
      older people, innovative treatment strategies will be needed in geriatric
      rehabilitation. A pilot study was designed to test the feasibility of robotic
      assisted rehabilitation after proximal humeral fractures. PATIENTS AND METHODS:
      Within a sample of 8 older patients (79.5 +/- 6.12 years), functional ability,
      quality and range of movement, self-rated impairment, quality of life, and user
      satisfaction were measured in an observational pre-/postdesign. During
      rehabilitation robotic-assisted training was applied. RESULTS: Training
      motivation and acceptance were high in this sample, showing improvements in
      functional ability (p = 0.03), quality of movement (p = 0.02), range of motion,
      self-evaluation (p = 0.01), and quality of life. CONCLUSION: This pilot study
      highlights the possible implementation of robotic-assisted rehabilitation after
      proximal humeral fractures in geriatric rehabilitation. The measurement and
      training protocol was suitable to document progress in rehabilitation.

PMID- 22159834
TI  - Bilateral heterotopic ossification after bilateral hip arthroplasty in a
      geriatric patient.
AB  - The case of a geriatric patient with total hip arthroplasty for coxarthrosis and
      an inpatient fall 12 days after the first operation is reported. Six weeks after
      the first operation, the patient reported new pain in the area of both hips and
      thighs. X-ray and scintigraphy confirmed the diagnosis of bilateral heterotopic
      ossification. NSAID therapy was started, and rapid improvement was observed. At
      discharge, the patient was able to walk with aids in- and outside. At the 12
      month follow-up, x-ray control showed Brooker state 3 for the right and 4 for the
      left hip. Walking ability did not change during follow-up.

PMID- 22159840
TI  - A rate law model for the explanation of complex pH oscillations in the thiourea
      iodate-sulfite flow system.
AB  - In a continuous flow stirred tank reactor (CSTR), the reaction of thiourea-iodate
      sulfite (TuIS) exhibits a rich variety of complex oscillations in pH. The
      transitions from 1(n) type oscillations to 1(3), 1(2) type and simple
      oscillations were observed on decreasing the flow rate gradually in small steps
      at 30.2  degrees C and 20.5  degrees C, respectively. The transitions from 1(n)
      type oscillations to 1(0)1(4), 1(0)1(3) type and simple oscillations were
      observed as well on increasing the temperature in small steps at a given flow
      rate. Based on the analogous iodate-sulfite-thiosulfate system a simple empirical
      rate law model is suggested to give a sound agreement between the experimental
      and simulated results on the complex oscillatory behaviour. A possible
      explanation of the emergence of the simple empirical rate law model from the
      mechanism of the individual reactions of the TuIS system is also discussed.

PMID- 22159835
TI  - [Recommendation of an assessment protocol to describe geriatric inpatient
      rehabilitation of lower limb mobility based on ICF: an interdisciplinary
      consensus process].
AB  - Because of the growing demand of geriatric rehabilitation, objective and clear
      indication decisions are needed with respect to limited financial resources. The
      aim of an interdisciplinary consensus group was to critically evaluate the most
      commonly used tests of functional performance of the lower limbs and to recommend
      useful tests to document progress of inpatient rehabilitation. Assessment of
      standing, walking, walking with a dual-task, sit-to-stand transfer, lying-to-sit
      to-stand transfer, and stair climbing were recommended to document functional
      performance of the lower limbs and to describe rehabilitation targets. Future
      research is needed, because reasonably validated assessment tools do not exist
      for all of these domains. In addition to a standardized assessment of physical
      capacity, physical activity and participation with regard to the International
      Classification of Functioning, Disability, and Health (ICF) context have to be
      assessed. Body fixed sensors seem to be a promising assessment tool to
      objectively document progress in rehabilitation.

PMID- 22159841
TI  - Isolation, characterization, and quantification of Clostridium kluyveri from the
      bovine rumen.
AB  - A strain of Clostridium kluyveri was isolated from the bovine rumen in a medium
      containing ethanol as an electron donor and acetate and succinate (common
      products of rumen fermentation) as electron acceptors. The isolate displayed a
      narrow substrate range but wide temperature and pH ranges atypical of ruminal
      bacteria and a maximum specific growth rate near the typical liquid dilution rate
      of the rumen. Quantitative real-time PCR revealed that C. kluyveri was widespread
      among bovine ruminal samples but was present at only very low levels (0.00002% to
      0.0002% of bacterial 16S rRNA gene copy number). However, the species was present
      in much higher levels (0.26% of bacterial 16S rRNA gene copy number) in lucerne
      silage (but not maize silage) that comprised much of the cows' diet. While C.
      kluyveri may account for several observations regarding ethanol utilization and
      volatile fatty acid production in the rumen, its population size and growth
      characteristics suggest that it is not a significant contributor to ruminal
      metabolism in typical dairy cattle, although it may be a significant contributor
      to silage fermentation. The ability of unadapted cultures to produce substantial
      levels (12.8 g L(-1)) of caproic (hexanoic) acid in vitro suggests that this
      strain may have potential for industrial production of caproic acid.

PMID- 22159842
TI  - Flexible photovoltaic cells based on a graphene-CdSe quantum dot nanocomposite.
AB  - We have fabricated the flexible photoelectrode by loading graphene sheets
      modified with CdSe QDs. A power conversion efficiency of ~0.6% and an incident
      photon to current conversion efficiency of 17% have been achieved for this
      flexible photovoltaic cell based on a graphene-CdSe nanocomposite.

PMID- 22159843
TI  - [Tibiocalcaneal arthrodesis using retrograde insertion of a compression nail].
AB  - OPERATION GOAL: Arthrodesis of the upper and lower ankle joint because of
      problematic bone positioning or failed arthrodesis. Osteosynthesis procedure
      using a retrograde compression nail. To achieve stable, fully weight-bearing
      osteosynthesis for early, pain-free mobilization. INDICATIONS: Rearthrodesis
      because of failure of the conventional arthrodesis technique and development of
      osteoarthritis of the lower ankle joint. Painful osteoarthritis of the upper
      ankle joint because of inadequate perfusion or a major bone defect because of
      sclerosis or necrosis. Primary arthrodesis because of facture of the lower leg
      (pilon tibial) with joint involvement and preexisting osteoarthritis.
      CONTRAINDICATIONS: Acute osteitis/osteomyelitis, sclerosis in the marrow of the
      distal tibia, malalignment of the distal tibial shaft and local soft tissue
      inflammation. SURGICAL TECHNIQUE: Preparation of the articular surface of the
      upper and lower ankle for arthrodesis using a transfibular approach. If
      necessary, correction of bone defects with iliac crest spongiosa. Stabile
      osteosynthesis by retrograde insertion of a compression nail. POSTOPERATIVE
      MANAGEMENT: A split lower leg cast on the 2nd postoperative day, mobilization of
      the patient with underarm crutches with floor contact for 2 weeks, then with
      application of a lower leg walking cast for 8 weeks with partial weight-bearing
      for 4 weeks and full weight-bearing for the last 4 weeks of cast fixation. X-ray
      controls immediately postoperatively, then after 6 and 12 weeks. RESULTS: From
      2006 to 2008, 12 patients (7 men, 5 women; mean age 59 years) with various
      indications were treated with retrograde insertion of a compression nail. All
      patients were routinely controlled radiologically and clinically after 2, 4, 8
      and 12 weeks. Follow-up was carried out at 6, 12 and 24 months. All arthrodeses
      showed osseous consolidation 16 weeks postoperatively. Ten patients were able to
      use full weight-bearing without pain after 12 weeks. Two patients reported
      experiencing pain after walking for 2 h. In total three complications occurred:
      one hindfoot healed with varus malalignment; one patient fell, fracturing the
      lower leg above the nail; one distal locking screw loosened.

PMID- 22159844
TI  - [Intramedullary nailing of the distal tibia illustrated with the Expert(TM) tibia
      nail].
AB  - OBJECTIVE: Restoration of axis, length, and rotation of the lower leg. Sufficient
      primary stability of the osteosynthesis for functional aftercare and to maintain
      joint mobility. Good bony healing in closed and open fractures. INDICATIONS:
      Closed and open fractures of the tibia and complete lower leg fractures distal to
      the isthmus (AO 42), extraarticular fractures of the distal tibia (AO 43
      A1/A2/A3), segmental fractures of the tibia with a fracture in the distal tibia,
      and certain intraarticular fractures of the distal tibia without impression of
      the joint line with the use of additional implants (AO 43 C1) CONTRAINDICATIONS:
      Patient in reduced general condition (e.g., bed ridden), flexion of the knee of
      less than 90 degrees , patients with knee arthroplasty of the affected leg,
      infection in the area of the nail's insertion, infection of the tibial cavity,
      complex articular fractures of the proximal or distal tibia with joint
      depression. SURGICAL TECHNIQUE: Closed reduction of the fracture preferably on a
      fracture table or using a distractor or an external fixation frame. If necessary,
      use pointed reduction clamps or sterile drapery. In some cases, additional
      implants like percutaneous small fragment screws, poller screws or k-wires are
      helpful. Open reduction is rarely necessary and must be avoided. Opening of the
      proximal tibia in line with the medullary canal. Canulated insertion of the
      Expert(TM) tibia nail (ETN; Synthes GmbH, Oberdorf, Switzerland) with reaming of
      the medullary canal. Control of axis, length, and rotation. Distal interlocking
      with the radiolucent drill and proximal interlocking with the targeting device.
      POSTOPERATIVE MANAGEMENT: Immediate mobilization of ankle and knee joint.
      Mobilization with 20 kg weight-bearing with crutches. X-ray control 6 weeks
      postoperatively and increased weight-bearing depending on the fracture status. In
      cases with simple fractures, good bony contact, or transverse fracture pattern,
      full weight-bearing at the end of week 6 is targeted. RESULTS: Between July 2004
      and May 2005, 180 patients were included in a multicenter study. The follow-up
      rate was 81% after 1 year. Of these, 91 fractures (50.6%) were located in the
      distal third of the tibia. In this segment, the rate of delayed union was 10.6%.
      Malalignment of > 5 degrees  was observed in 5.4%. A secondary malalignment after
      initial good reduction was detected in only 1.1% of all cases. The implant
      specific risk for screw breakage was 3.2%. One patient sustained a deep
      infection. If additional fibula plating was performed an 8-fold higher risk for
      delayed bone healing was observed (95%CI: 2.9-21.2, p< 0.001). If the fracture of
      the fibula was at the same height as on the tibia, the risk for delayed healing
      was even 14-fold (95% CI: 3.4-62.5, p< 0.001). Biomechanically plating of the
      fibula does not increase stability in suprasyndesmal distal tibia-fibular
      fractures treated with an intramedullary nail. Using the ETN with its optimized
      locking options, fibula plating is not recommended, thus, avoiding soft tissue
      problems and potentially delayed bone healing.

PMID- 22159845
TI  - HAS3-induced accumulation of hyaluronan in 3D MDCK cultures results in mitotic
      spindle misorientation and disturbed organization of epithelium.
AB  - The amount of hyaluronan (HA) is low in simple epithelia under normal conditions,
      but during tumorigenesis, trauma or inflammation HA is increased on the
      epithelial cells and surrounding stroma. Excessive HA in epithelia is suggested
      to interfere with cell-cell adhesions, resulting in disruption of the epithelial
      barrier function. In addition, stimulated HA synthesis has been correlated with
      epithelial-to-mesenchymal transition and invasion of cancer cells. However, the
      effects of HA overload on normal epithelial morphogenesis have not been
      characterized in detail. Madin-Darby canine kidney (MDCK) cells form polarized
      epithelial cysts, when grown in a 3-dimensional (3D) matrix. These cells were
      used to investigate whether stimulated HA synthesis, induced by stable
      overexpression of GFP-HAS3, influences cell polarization and epithelial
      morphogenesis. GFP-HAS3 expression in polarized MDCK cells resulted in active HA
      secretion at apical and basolateral membrane domains. HA-deposits interfered with
      the formation of cell-cell junctions, resulting in impaired barrier function. In
      3D cyst cultures, HA accumulated into apical lumina and was also secreted from
      the basal side. The HAS3-expressing cysts failed to form a single lumen and
      instead displayed multiple small lumina. This phenotype was correlated with
      aberrant mitotic spindle orientation in dividing cells. The results of this study
      indicate that excess pericellular HA disturbs the normal cell-cell and cell-ECM
      interactions in simple epithelia, leading to aberrant epithelial morphogenesis.
      The morphological abnormalities observed in 3D epithelial cultures upon
      stimulated HAS3 expression may be related to premalignant changes, including
      intraluminal invasion and deregulated epithelialization, probably mediated by the
      mitotic spindle orientation defects.

PMID- 22159848
TI  - Orthopaedic journals and conflict of interest.

PMID- 22159849
TI  - A prospective randomized trial comparing nonoperative treatment with volar
      locking plate fixation for displaced and unstable distal radial fractures in
      patients sixty-five years of age and older.
AB  - BACKGROUND: Despite the recent trend toward the internal fixation of distal
      radial fractures in older patients, the currently available literature lacks
      adequate randomized trials examining whether open reduction and internal fixation
      (ORIF) with a volar locking plate is superior to nonoperative (cast) treatment.
      The purpose of the present randomized clinical trial was to compare the outcomes
      of two methods that were used for the treatment of displaced and unstable distal
      radial fractures in patients sixty-five years of age or older: (1) ORIF with use
      of a volar locking plate and (2) closed reduction and plaster immobilization
      (casting). METHODS: A prospective randomized study was performed. Seventy-three
      patients with a displaced and unstable distal radial fracture were randomized to
      ORIF with a volar locking plate (n = 36) or closed reduction and cast
      immobilization (n = 37). The outcome was measured on the basis of the Patient
      Rated Wrist Evaluation (PRWE) score; the Disabilities of the Arm, Shoulder and
      Hand (DASH) score; the pain level; the range of wrist motion; the rate of
      complications; and radiographic measurements including dorsal radial tilt, radial
      inclination, and ulnar variance. RESULTS: There were no significant differences
      between the groups in terms of the range of motion or the level of pain during
      the entire follow-up period (p > 0.05). Patients in the operative treatment group
      had lower DASH and PRWE scores, indicating better wrist function, in the early
      postoperative time period (p < 0.05), but there were no significant differences
      between the groups at six and twelve months. Grip strength was significantly
      better at all times in the operative treatment group (p < 0.05). Dorsal radial
      tilt, radial inclination, and radial shortening were significantly better in the
      operative treatment group than in the nonoperative treatment group at the time of
      the latest follow-up (p < 0.05). The number of complications was significantly
      higher in the operative treatment group (thirteen compared with five, p < 0.05).
      CONCLUSIONS: At the twelve-month follow-up examination, the range of motion, the
      level of pain, and the PRWE and DASH scores were not different between the
      operative and nonoperative treatment groups. Patients in the operative treatment
      group had better grip strength through the entire time period. Achieving
      anatomical reconstruction did not convey any improvement in terms of the range of
      motion or the ability to perform daily living activities in our cohorts.

PMID- 22159851
TI  - Prevalence of pseudotumor in asymptomatic patients after metal-on-metal hip
      arthroplasty.
AB  - BACKGROUND: The cause of recently reported pseudotumor formation in patients with
      metal-on-metal hip replacements is unknown. It has been postulated that there is
      an association between elevated levels of serum metal ions and pseudotumor
      formation. The primary purpose of this study was to assess the prevalence of
      pseudotumor formation in asymptomatic patients with a metal-on-metal total hip
      replacement after a minimum duration of follow-up of two years. A secondary
      purpose was to assess whether a correlation exists between elevated serum metal
      ion levels and pseudotumor formation. METHODS: In the present study, the
      prevalence of pseudotumor formation, as detected with ultrasound, was evaluated
      for thirty-one asymptomatic patients with a metal-on-metal total hip
      arthroplasty, twenty-four asymptomatic patients with a metal-on-polyethylene
      total hip arthroplasty, and twenty asymptomatic patients with a metal-on-metal
      hip resurfacing arthroplasty. Serum levels of cobalt and chromium were measured
      in the metal-on-metal total hip arthroplasty and hip resurfacing arthroplasty
      groups. RESULTS: Ten patients (32%) in the metal-on-metal total hip arthroplasty
      group had a solid or cystic mass, with another three patients (10%) having a
      substantial fluid collection. Five patients (25%) in the hip resurfacing
      arthroplasty group had a solid or cystic mass, with another patient (5%) having a
      fluid collection. Pseudotumor formation was significantly more frequent in the
      metal-on-metal total hip arthroplasty group compared with the metal-on
      polyethylene total hip arthroplasty group (p = 0.015). We did not detect a
      significant correlation between the serum metal ion levels and the size of
      pseudotumor abnormality. The median serum metal ion level was greater in patients
      with pseudotumor formation than it was in those without pseudotumor formation,
      but the difference was not significant. CONCLUSIONS: We recommend high-resolution
      ultrasound surveillance of all asymptomatic patients with a metal-on-metal
      implant that is known to result in high serum metal ion levels. Once a metal-on
      metal implant is known to be associated with high serum metal ions, the
      measurement of ion levels does not helpfully contribute to surveillance.

PMID- 22159850
TI  - Variations in the use of internal fixation for distal radial fracture in the
      United States medicare population.
AB  - BACKGROUND: Distal radial fractures affect an estimated 80,000 elderly Americans
      each year. Although the use of internal fixation for the treatment of distal
      radial fractures is becoming increasingly common, there have been no population
      based studies to explore the dissemination of this technique. The aims of our
      study were to determine the current use of internal fixation for the treatment of
      distal radial fractures in the Medicare population and to examine regional
      variations and other factors that influence use of this treatment. We
      hypothesized that internal fixation of distal radial fractures would be used less
      commonly in male and black populations compared with other populations because
      the prevalence of osteoporosis is lower in these populations, and that use of
      internal fixation would be correlated with the percentage of the patients who
      were treated by a hand surgeon in a particular region. METHODS: We performed an
      analysis of complete 2007 Medicare data to determine the percentage of distal
      radial fractures that were treated with internal fixation in each hospital
      referral region. We then analyzed the association of patient and physician
      factors with the type of fracture treatment received, both nationally and within
      each hospital referral region. RESULTS: We identified 85,924 Medicare
      beneficiaries with a closed distal radial fracture who met the inclusion
      criteria, and 17.0% of these patients were treated with internal fixation.
      Fractures were significantly less likely to be treated with internal fixation in
      men than in women (odds ratio, 0.84; 95% confidence interval, 0.80 to 0.89) and
      in black patients than in white patients (odds ratio, 0.74; 95% confidence
      interval, 0.65 to 0.85). Patients were more likely to be treated with internal
      fixation rather than with another treatment if they were treated by a hand
      surgeon than if they were treated by an orthopaedic surgeon who was not a hand
      surgeon (odds ratio, 2.49; 95% confidence interval, 2.29 to 2.70). Use of
      internal fixation ranged from 4.6% to 42.1% (nearly a ten-fold difference) among
      hospital referral regions. The percentage of patients treated with internal
      fixation within a hospital referral region was positively correlated with the
      percentage of patients in that region who were treated by a hand surgeon
      (correlation coefficient, 0.34; p < 0.0001). CONCLUSIONS: The use of internal
      fixation for the treatment of a distal radial fracture differs widely among
      geographical regions and patient populations. Such variations highlight the need
      for improved comparative-effectiveness data to guide the treatment of this
      fracture.

PMID- 22159852
TI  - Angular-stable locked intramedullary nailing of two-part surgical neck fractures
      of the proximal part of the humerus. A multicenter retrospective observational
      study.
AB  - BACKGROUND: The ideal fixation technique for the treatment of proximal humeral
      fractures remains unclear. In the present study, we evaluated the experience of
      three surgeons with the treatment of two-part surgical neck fractures with
      angular-stable intramedullary fixation. METHODS: Forty-eight patients with forty
      eight Neer two-part surgical neck proximal humeral fractures were managed with
      locked angular-stable intramedullary nail fixation by three surgeons. Shoulder
      pain and outcomes were quantified with Constant scores and standard radiographs.
      RESULTS: Thirty-eight patients (including twenty-eight female patients and ten
      male patients) with a mean age of sixty-five years were followed for at least
      twelve months (mean, twenty months; range, twelve to thirty-six months). All
      fractures healed primarily. The mean follow-up Constant score (and standard
      deviation) was 71 +/- 12 points (range, 37 to 88 points), with a mean age
      adjusted Constant score of 97% (range, 58% to 119%). The mean Constant pain score
      was 13 +/- 2.2 (possible range, 0 to 15 points, with 15 points representing no
      pain). The mean forward flexion was 132 degrees  +/- 22 degrees . All fractures
      but one healed with a neck-shaft angle of >=125 degrees . CONCLUSIONS: Patients
      who were managed with locked angular-stable intramedullary nailing of two-part
      surgical neck proximal humeral fractures via an articular entry point had
      reliable fracture-healing, favorable clinical outcomes, and little residual
      shoulder pain.

PMID- 22159853
TI  - The in vivo linear and volumetric wear of hip resurfacing implants revised for
      pseudotumor.
AB  - BACKGROUND: Metal-on-metal arthroplasty-related pseudotumors can cause severe
      local destruction of bone and soft tissues. The cause of pseudotumors is unknown,
      although some authors have implicated metal wear debris. The aim of this study
      was to measure the location and magnitude of wear on resurfacing devices that
      were retrieved during revision procedures for pseudotumor (the pseudotumor group)
      and for other reasons (the control group). METHODS: We examined thirty-six hip
      resurfacing implants, which were divided into two groups: eighteen implants from
      patients with a diagnosis of pseudotumor and eighteen control implants. Implant
      orientation and patient demographics were recorded. Three-dimensional,
      contactless metrology was used to scan the surface of the femoral and acetabular
      components to a resolution of 20 nm. Linear and volumetric wear were measured,
      and the components were examined for evidence of edge wear. RESULTS: There was
      three times more total linear wear and over six times more total volumetric wear
      of the femoral and acetabular components in the pseudotumor group as compared
      with that in the control group. The mean linear wear rate and standard deviation
      of the femoral components in the pseudotumor group (8.4 +/- 8.7 MUm/yr) were
      significantly greater than those in the control group (2.9 +/- 3.9 MUm/yr; p =
      0.01). The mean volumetric wear rate of the femoral components was also
      significantly greater in the pseudotumor group (3.3 +/- 5.7 mm3/yr) than it was
      in the control group (0.8 +/- 1.2 mm3/yr; p = 0.009). Seventeen of eighteen
      subjects in the pseudotumor group had edge wear, compared with six of eighteen in
      the control group (p < 0.001). CONCLUSIONS: Implants that were retrieved because
      of pseudotumor had a significantly higher wear rate and prevalence of edge wear
      than the control implants did. There was a strong association between pseudotumor
      and the high levels of wear debris that are generated during edge-loading.
      However, not all patients with high wear developed pseudotumors, and not all
      pseudotumors had high wear; therefore, other factors are most likely involved in
      the cause of pseudotumors.

PMID- 22159854
TI  - Anabolic steroids reduce muscle damage caused by rotator cuff tendon release in
      an experimental study in rabbits.
AB  - BACKGROUND: Muscles of the rotator cuff undergo retraction, atrophy, and fatty
      infiltration after a chronic tear, and a rabbit model has been used to
      investigate these changes. The purpose of this study was to test the hypothesis
      that the administration of anabolic steroids can diminish these muscular changes
      following experimental supraspinatus tendon release in the rabbit. METHODS: The
      supraspinatus tendon was released in twenty New Zealand White rabbits.
      Musculotendinous retraction was monitored over a period of six weeks. The seven
      animals in group I had no additional intervention, the six animals in group II
      had local and systemic administration of nandrolone decanoate, and the seven
      animals in group III had systemic administration of nandrolone decanoate during
      the six weeks. Two animals (group III) developed a postoperative infection and
      were excluded from the analysis. At the time that the animals were killed, in
      vivo muscle performance as well as imaging and histological muscle changes were
      investigated. RESULTS: The mean supraspinatus retraction was higher in group I
      (1.8 cm; 95% confidence interval: 1.64, 2.02 cm) than in group II (1.5 cm; 95%
      confidence interval: 1.29, 1.81 cm) or III (1.2 cm; 95% confidence interval:
      0.86, 1.54 cm). Histologically, no fatty infiltration was measured in either
      treated group II (mean, 2.2%; range, 0% to 8%) or III (mean, 1%; range, 0% to
      3.4%), but it was measured in the untreated group I (mean, 5.9%; range, 0% to
      14.1%; p = 0.031). The radiographic cross-sectional area indicating atrophy and
      the work of the respective muscle during one standardized contraction with
      supramaximal stimulation decreased in all groups, but the work of the muscle was
      ultimately highest in group III. CONCLUSIONS: To our knowledge, this is the first
      documentation of partial prevention of important muscle alterations after
      retraction of the supraspinatus musculotendinous unit caused by tendon
      disruption. Nandrolone decanoate administration in the phase after tendon release
      prevented fatty infiltration of the supraspinatus muscle and reduced functional
      muscle impairment caused by myotendinous retraction in this rabbit rotator cuff
      model, but two of seven rabbits that received the drug developed infections.

PMID- 22159855
TI  - The treatment of low-energy femoral shaft fractures: a prospective study
      comparing the "walking spica" with the traditional spica cast.
AB  - BACKGROUND: A single-leg, walking hip spica cast has been shown to be a safe and
      effective treatment for a low-energy femoral shaft fracture in young children. We
      designed a prospective cohort trial comparing walking and traditional hip spica
      casting to determine whether a walking hip spica cast was superior to a
      traditional hip spica cast following a low-energy femoral shaft fracture in
      children one to six years old. METHODS: We studied forty-five consecutive low
      energy femoral shaft fractures during a three-year period in children one to six
      years old. Three surgeons treated their patients with a walking hip spica cast,
      and three other surgeons treated their patients with a traditional spica cast.
      Complications and subsequent interventions were recorded prospectively.
      Caregivers were asked to complete the validated Impact on Family Scale as well as
      a ten-item questionnaire developed by the authors at the time of cast removal.
      RESULTS: Forty-five patients with a low-energy fracture were enrolled in the
      study. Nineteen patients were treated with a walking hip spica cast and twenty
      six, with a traditional hip spica cast. The two cohorts were similar with respect
      to age, length of hospital stay, time to initial callus formation, and time to
      fracture union. Two children treated with a traditional hip spica cast and no
      children in the walking hip spica group returned to the operating room for the
      treatment of spontaneous loss of fracture reduction. Five of the nineteen
      children treated with a walking hip spica cast and one of the twenty-six treated
      with a traditional hip spica cast required wedge adjustment of the cast in the
      clinic to treat fracture malalignment (p = 0.04). One patient treated with a
      walking hip spica cast required repeat reduction in the operating room because of
      overcorrection during wedge adjustment. The malunion rate did not differ
      significantly between the groups (three of twenty-six in the traditional hip
      spica group compared with none of nineteen in the walking hip spica group). All
      patients treated with a walking hip spica cast were able to crawl in the cast,
      and 71% (twelve of seventeen) were able to walk. Use of the traditional hip spica
      cast resulted in a significantly greater care burden for the family as measured
      with use of the Impact on Family Scale (43.3 for the traditional hip spica group
      compared with 35.6 for the walking hip spica group, p = 0.04). Insurance-funded
      ambulance transportation was needed for eleven of the twenty-six patients treated
      with a traditional hip spica cast compared with none of the nineteen patients
      treated with a walking hip spica cast (p = 0.001). CONCLUSIONS: The walking hip
      spica cast and the traditional hip spica cast resulted in similar orthopaedic
      outcomes, and the walking hip spica cast resulted in a lower care burden for the
      family. Surgeons and families should be aware that use of a walking hip spica
      cast rather than a traditional hip spica cast may be associated with a greater
      likelihood that wedge adjustment of the cast will be necessary to treat fracture
      malalignment.

PMID- 22159856
TI  - A population-based comparison of the incidence of adverse outcomes after
      simultaneous-bilateral and staged-bilateral total knee arthroplasty.
AB  - BACKGROUND: It is unclear whether simultaneous-bilateral total knee arthroplasty
      is as safe as staged-bilateral arthroplasty is. We are aware of no randomized
      trials comparing the safety of these surgical strategies. The purpose of this
      study was to retrospectively compare these two strategies, with use of an
      intention-to-treat approach for the staged-bilateral arthroplasty cohort.
      METHODS: We used linked hospital discharge data to compare the safety of
      simultaneous-bilateral and staged-bilateral knee arthroplasty procedures
      performed in California between 1997 and 2007. Estimates were generated to take
      into account patients who had planned to undergo staged-bilateral arthroplasty
      but never underwent the second procedure because of death, a major complication,
      or elective withdrawal. Hierarchical logistic regression modeling was used to
      adjust the comparisons for patient and hospital characteristics. The principal
      outcomes of interest were death, a major complication involving the
      cardiovascular system, and a periprosthetic knee infection or mechanical
      malfunction requiring revision surgery. RESULTS: Records were available for
      11,445 simultaneous-bilateral arthroplasty procedures and 23,715 staged-bilateral
      procedures. On the basis of an intermediate estimate of the number of
      complications that occurred after the first procedure in a staged-bilateral
      arthroplasty, patients who underwent simultaneous-bilateral arthroplasty had a
      significantly higher adjusted odds ratio (OR) of myocardial infarction (OR = 1.6,
      95% confidence interval [CI] = 1.2 to 2.2) and of pulmonary embolism (OR = 1.4,
      95% CI = 1.1 to 1.8), similar odds of death (OR = 1.3, 95% CI = 0.9 to 1.9) and
      of ischemic stroke (OR = 1.0, 95% CI = 0.6 to 1.6), and significantly lower odds
      of major joint infection (OR = 0.6, 95% CI = 0.5 to 0.7) and of major mechanical
      malfunction (OR = 0.7, 95% CI = 0.6 to 0.9) compared with patients who planned to
      undergo staged-bilateral arthroplasty. The unadjusted thirty-day incidence of
      death or a coronary event was 3.2 events per thousand patients higher after
      simultaneous-bilateral arthroplasty than after staged-bilateral arthroplasty, but
      the one-year incidence of major joint infection or major mechanical malfunction
      was 10.5 events per thousand lower after simultaneous-bilateral arthroplasty.
      CONCLUSIONS: Simultaneous-bilateral total knee arthroplasty was associated with a
      clinically important reduction in the incidence of periprosthetic joint infection
      and malfunction within one year after arthroplasty, but it was associated with a
      moderately higher risk of an adverse cardiovascular outcome within thirty days.
      If patients who are at higher risk for cardiovascular complications can be
      identified, simultaneous-bilateral knee arthroplasty may be the preferred
      surgical strategy for the remaining lower-risk patients.

PMID- 22159857
TI  - Responsiveness of the SF-36 and WOMAC following periacetabular osteotomy for
      acetabular dysplasia.
AB  - BACKGROUND: Periacetabular osteotomy is a relatively common reconstructive
      procedure for the adolescent or young adult with acetabular dysplasia. Although
      several measures have been used to characterize the outcome, the responsiveness
      of these measures in this population has not been determined. The purpose of this
      study was to estimate the responsiveness of the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) and the Short Form-36 (SF-36) in
      patients with acetabular dysplasia treated with periacetabular osteotomy.
      METHODS: Eighty-three patients with acetabular dysplasia treated with
      periacetabular osteotomy between 2000 and 2005 completed the WOMAC and SF-36 both
      preoperatively and postoperatively. The scores on each domain of these outcome
      measures were calculated and analyzed to determine the parameters of
      responsiveness, including the minimal detectable change at the 90% confidence
      level. RESULTS: The mean duration of follow-up was 1.9 years. Comparison of the
      effect size, standardized response mean, and minimal detectable change for the SF
      36 and WOMAC demonstrated that the WOMAC was more sensitive to change than the SF
      36 was, particularly in the physical function domain (minimal detectable change,
      9.1) and the pain domain (minimal detectable change, 5.5). Only one of the eight
      domains of the SF-36, bodily pain, demonstrated a change in outcome that exceeded
      the minimal detectable change, which was 2.38. CONCLUSIONS: Both the WOMAC and
      the SF-36 demonstrated adequate responsiveness to change over time in patients
      with acetabular dysplasia treated with periacetabular osteotomy, although the
      WOMAC was more sensitive to change. These results indicate that the WOMAC is
      sufficiently responsive to be used as a joint-specific measure for assessing
      changes following periacetabular osteotomy for the treatment of acetabular
      dysplasia.

PMID- 22159858
TI  - The osteoinductivity of silicate-substituted calcium phosphate.
AB  - BACKGROUND: The osteoinductivity of silicate-substituted calcium phosphate and
      stoichiometric calcium phosphate was investigated with use of ectopic
      implantation. Implants with a macroporosity of 80% and a strut porosity of 30%
      were inserted into sites located in the left and right paraspinal muscles of six
      female sheep. METHODS: After twelve weeks in vivo, a longitudinal thin section
      was prepared through the center of each implant. Bone formation within the
      implant, bone formation in contact with the implant surface, and implant
      resorption were quantified with use of a line intersection method. The specimens
      were also analyzed with use of backscattered scanning electron microscopy and
      energy-dispersive x-ray analysis. RESULTS: Silicate substitution had a
      significant effect on the formation of bone both within the implant and on the
      implant surface during the twelve-week period. Bone area within the implant was
      greater in the silicate-substituted calcium phosphate group (mean, 7.65% +/-
      3.2%) than in the stoichiometric calcium phosphate group (0.99% +/- 0.9%, p =
      0.01). The amount of bone formed at the surface of the implant was also
      significantly greater in the silicate-substituted calcium phosphate group (mean,
      26.00% +/- 7.8%) than in the stoichiometric calcium phosphate group (2.2% +/-
      2.0%, p = 0.01). Scanning electron microscopy demonstrated bone formation within
      pores that were <5 MUm in size, and energy-dispersive x-ray analysis confirmed
      the presence of silicon within the new bone in the silicate-substituted calcium
      phosphate group. CONCLUSIONS: The formation of bone within muscle during the
      twelve-week period showed both silicate-substituted calcium phosphate and
      stoichiometric calcium phosphate to be osteoinductive in an ovine model. Silicate
      substitution significantly increased the amount of bone that formed and the
      amount of bone attached to the implant surface. New bone formation occurred
      through an intramembranous process within the implant structure.

PMID- 22159859
TI  - Autogenous bone graft: donor sites and techniques.
AB  - Autogenous cancellous bone graft provides an osteoconductive, osteoinductive, and
      osteogenic substrate for filling bone voids and augmenting fracture-healing.The
      iliac crest remains the most frequently used site for bone-graft harvest, but the
      proximal part of the tibia, distal end of the radius, distal aspect of the tibia,
      and greater trochanter are alternative donor sites that are particularly useful
      for bone-grafting in the ipsilateral extremity.The most common complication
      associated with the harvest of autogenous bone graft is pain at the donor site,
      with less frequent complications including nerve injury, hematoma, infection, and
      fracture at the donor site.Induced membranes is a method that uses a temporary
      polymethylmethacrylate cement spacer to create a bone-graft-friendly environment
      to facilitate graft incorporation, even in large segmental defects.

PMID- 22159860
TI  - Ankle dorsiflexor function after plantar flexor surgery in children with cerebral
      palsy.
AB  - BACKGROUND: Surgical lengthening is used to address both overactivity and
      shortening of the spastic agonist muscle in children with cerebral palsy. It has
      been presumed that the function of the antagonist muscle will improve when the
      spastic agonist muscle has been surgically lengthened. The purposes of the
      current study were to use quantitative gait analysis to determine the prevalence
      of the ankle dorsiflexor muscles (antagonist) dysfunction during the swing phase
      of the gait cycle and to analyze how this function is affected following surgical
      lengthening of the ankle plantar flexor muscles (agonist). METHODS: The study
      design was a retrospective, cohort series of fifty-three children with cerebral
      palsy who underwent gait analysis before and after surgical lengthening of the
      gastrocnemius-soleus muscle group. Data from the physical examination, gait study
      kinematics, and dynamic electromyography in swing phase were analyzed. RESULTS:
      The mean age at the time of the initial gait analysis was eight years and eleven
      months. Significant improvements were noted in ankle dorsiflexion passive range
      of motion (p < 0.001), ankle dorsiflexor selective control (p = 0.002), ankle
      dorsiflexor strength (p = 0.001), and peak and mean ankle dorsiflexion in swing
      phase (p < 0.001 for each) following ankle plantar flexor lengthening surgery.
      Active ankle dorsiflexor function in swing phase was present in 79% of the
      extremities prior to ankle plantar flexor surgery. Swing phase dorsiflexor
      function was present in 96% of the extremities following surgery, with ten
      extremities improving from absent to present. CONCLUSIONS: The kinematic data
      support the clinical impression that ankle dorsiflexion during swing phase is
      improved following ankle plantar flexor lengthening surgery in children with
      cerebral palsy. In the majority of patients, this was a consequence of the
      correction of a fixed equinus contracture of the ankle plantar flexors that was
      constraining preexisting ankle dorsiflexor function. Weakness of all of the
      muscles is common, and surgical lengthening should only be considered for the
      correction of recalcitrant muscle contractures. Improved function of the
      antagonist muscle should be anticipated and optimized by appropriately focused
      strength training and other modalities during rehabilitation.

PMID- 22159861
TI  - Gangrenous testicular torsion, presenting as refusal to bear weight, in a
      fourteen-month-old child: a case report.

PMID- 22159862
TI  - Treatment of glenohumeral arthrosis and inferior shoulder subluxation in an adult
      with cerebral palsy: a case report.

PMID- 22159863
TI  - Occupational hazards to the pregnant orthopaedic surgeon.
AB  - The number of female orthopaedic residents and orthopaedic surgeons has increased
      substantially. Concerns have been raised regarding the effect of the work
      environment on the health of the female orthopaedic surgeon and her fetus or
      neonate. Occupational risks, and specifically risks to the pregnant orthopaedic
      surgeon, are becoming an important issue in medicine. Such risks include exposure
      to methylmethacrylate (MMA), anesthetic gases, blood-borne pathogens, radiation,
      emotional stress, and physical stress. Awareness of and knowledge about such
      exposures are needed for the pregnant orthopaedic surgeon to make informed
      decisions about her occupational exposures and to be proactive about her own and
      her child's health.

PMID- 22159864
TI  - Orthopaedic resident and program director opinions of resident duty hours: a
      national survey.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      established national guidelines for resident duty hours in July 2003. Following
      an Institute of Medicine report in December 2008, the ACGME recommended further
      restrictions on resident duty hours that went into effect in July 2011. We
      conducted a national survey to assess the opinions of orthopaedic residents and
      of directors of residency and fellowship programs in the U.S. regarding the 2003
      and 2011 ACGME resident duty-hour regulations and the effects of these
      regulations on resident education and patient care. METHODS: A fifteen-item
      questionnaire was electronically distributed by the Candidate, Resident, and
      Fellow Committee of the American Academy of Orthopaedic Surgeons (AAOS) to all
      U.S. orthopaedic residents (n = 3860) and directors of residency programs (n =
      184) and fellowship programs (n = 496) between January and April 2011. Thirty
      four percent (1314) of the residents and 27% (185) of the program directors
      completed the questionnaire. Statistical analyses were performed to detect
      differences between the responses of residents and program directors and between
      the responses of junior and senior residents. RESULTS: The responses of
      orthopaedic residents and program directors differed significantly (p < 0.001)
      for fourteen of the fifteen survey items. The responses of residents and program
      directors were divergent for questions regarding the 2003 rules. Overall, 71% of
      residents thought that the eighty-hour work week was appropriate, whereas only
      38% of program directors agreed (p < 0.001). Most program directors (70%) did not
      think that the 2003 duty-hour rules had improved patient care, whereas only 24%
      of residents responded in the same way (p < 0.001). The responses of residents
      and program directors to questions regarding the 2011 duty-hour rules were
      generally compatible, but the degree to which they perceived the issues was
      different. Only 18% of residents and 19% of program directors thought that the
      suggested strategic five-hour evening rest period implemented in July 2011 for on
      call residents was appropriate (p > 0.05), and both groups (84% of residents and
      74% of program directors) also disagreed with the limitation of intern shifts to
      sixteen hours (p < 0.001). Seventy percent of residents and 79% of program
      directors thought that the new duty-hour regulations would result in an increased
      number of handoffs that would be detrimental to patient care (p < 0.001). The
      mean responses of junior residents and senior residents differed for eight of the
      fifteen survey items (p < 0.001), with the responses of senior residents more
      closely resembling those of program directors on six of these eight questions.
      The mean responses and percentiles for the survey items did not differ
      significantly between residency directors and fellowship directors (p > 0.05).
      CONCLUSIONS: This national survey indicated significant differences between the
      opinions of orthopaedic residents and program (residency and fellowship)
      directors regarding the 2003 ACGME resident duty-hour regulations and the effects
      of these regulations on resident education and patient care. However, both
      residents and program directors agreed that the further reductions in duty hours
      in the 2011 rules may be detrimental to resident education and patient care.

PMID- 22159865
TI  - Hip resurfacing arthroplasty: moving toward sex-specific surgery?

PMID- 22159866
TI  - Important preliminary findings on the potential role for nandrolone decanoate in
      the treatment of chronic rotator cuff tears.

PMID- 22159867
TI  - Transcriptional and post-transcriptional regulation of betaIII-tubulin protein
      expression in relation with cell cycle-dependent regulation of tumor cells.
AB  - The expression of betaIII-tubulin (TUBB3) is generally restricted to neurons, but
      its mRNA is often expressed at low levels in non-neuronal cells. Interestingly,
      however, a number of non-neural tumors occasionally express high levels of TUBB3
      protein, leading to a significant resistance to taxane derivatives. However, the
      molecular mechanisms controlling TUBB3 expression and its turnover during normal
      cell growth are largely unknown. Here, we present evidence that TUBB3 expression
      occurs in a cell cycle-dependent manner, and that its protein levels are
      controlled by the ubiquitin-proteasome system. Both mRNA and protein of TUBB3
      accumulated around the G2/M stage of the cell cycle, and reduction of TUBB3
      expression by siRNA resulted in partial inhibition of cell growth. Furthermore,
      the cell cycle-dependent expression of TUBB3 was mediated by the RE-1-silencing
      transcription factor REST through its binding to the RE-1 element that is present
      in the first intron of the TUBB3 gene. These results demonstrate a novel role of
      TUBB3 in cell cycle progression in non-neuronal cells, and further suggest that
      dysregulation of the REST-TUBB3 system could be a primary cause of the TUBB3
      overexpression.

PMID- 22159868
TI  - Lectin genes in the Frankia alni genome.
AB  - Frankia alni strain ACN14a's genome was scanned for the presence of determinants
      involved in interactions with its host plant, Alnus spp. One such determinant
      type is lectin, proteins that bind specifically to sugar motifs. The genome of F.
      alni was found to contain 7 such lectin-coding genes, five of which were of the
      ricinB-type. The proteins coded by these genes contain either only the lectin
      domain, or also a heat shock protein or a serine-threonine kinase domain
      upstream. These lectins were found to have several homologs in Streptomyces spp.,
      and a few in other bacterial genomes among which none in Frankia EAN1pec and CcI3
      and two in strain EUN1f. One of these F. alni genes, FRAAL0616, was cloned in E.
      coli, fused with a reporter gene yielding a fusion protein that was found to bind
      to both root hairs and to bacterial hyphae. This protein was also found to modify
      the dynamics of nodule formation in A. glutinosa, resulting in a higher number of
      nodules per root. Its role could thus be to permit binding of microbial cells to
      root hairs and help symbiosis to occur under conditions of low Frankia cell
      counts such as in pioneer situations.

PMID- 22159869
TI  - Metabolism of alprazolam (a marker of CYP3A4) in hemodialysis patients with
      persistent inflammation.
AB  - OBJECTIVE: To investigate the impact of persistent inflammation in hemodialysis
      (HD) patients on the pharmacokinetics of alprazolam, a cytochrome P450 (CYP) 3A4
      substrate, and its metabolites and the role of HD in the impact of persistent
      inflammation in this clinical context. METHODS: The study population comprised 26
      HD patients (mean age 64 years, range 27-79 years; 19 men, 7 women) who were
      given 1 mg of alprazolam orally in the evening before the day of HD. Unconjugated
      and conjugated alprazolam and its 4-hydroxy and alpha-hydroxy metabolites were
      measured by liquid chromatography-mass spectrometry at 10, 34 (start of HD) and
      38 (end of HD) h after intake. C-reactive protein (CRP) was measured weekly
      beginning 2 months before study initiation, and alpha 1-acid glycoprotein and
      4beta-hydroxycholesterol were measured at baseline. CYP3A4 activity was estimated
      as the ratio of unconjugated alprazolam to 4-hydroxyalprazolam between 10 and 34
      h following alprazolam intake. RESULTS: After a single dose of alprazolam, plasma
      concentrations of unconjugated alprazolam and its metabolites decreased
      gradually, and unconjugated 4-hydroxyalprazolam was eliminated more rapidly than
      unconjugated alprazolam by HD. In contrast, the plasma concentrations of
      conjugated alprazolam and its conjugated metabolites increased during the 34 h
      following drug intake and the subsequent HD decreased their levels by almost 80%.
      The ratio of unconjugated alprazolam to 4-hydroxyalprazolam was correlated with
      CRP levels (r(s) = 0.49, P = 0.01). There was no significant correlation between
      CYP3A4 activity measured by alprazolam (4-hydroxylation) and alpha 1-acid
      glycoprotein or 4beta-hydroxycholesterol. Conjugated alprazolam was also found in
      the plasma. CONCLUSIONS: The correlation between CYP3A4 activity (assessed by
      alprazolam 4-hydroxylation) and CRP level suggests that inflammation may
      downregulate CYP3A4 activity. If confirmed, this could have major implications
      for drug dosing in persistently inflamed patients.

PMID- 22159870
TI  - Response of dominant grass and shrub species to water manipulation: an
      ecophysiological basis for shrub invasion in a Chihuahuan Desert grassland.
AB  - Increases in woody vegetation and declines in grasses in arid and semi-arid
      ecosystems have occurred globally since the 1800s, but the mechanisms driving
      this major land-cover change remain uncertain and controversial. Working in a
      shrub-encroached grassland in the northern Chihuahuan Desert where grasses and
      shrubs typically differ in leaf-level nitrogen allocation, photosynthetic
      pathway, and root distribution, we asked if differences in leaf-level
      ecophysiology could help explain shrub proliferation. We predicted that the
      relative performance of grasses and shrubs would vary with soil moisture due to
      the different morphological and physiological characteristics of the two life
      forms. In a 2-year experiment with ambient, reduced, and enhanced precipitation
      during the monsoon season, respectively, the encroaching C(3) shrub (honey
      mesquite Prosopis glandulosa) consistently and substantially outperformed the
      historically dominant C(4) grass (black grama Bouteloua eriopoda) in terms of
      photosynthetic rates while also maintaining a more favorable leaf water status.
      These differences persisted across a wide range of soil moisture conditions,
      across which mesquite photosynthesis was decoupled from leaf water status and
      moisture in the upper 50 cm of the soil profile. Mesquite's ability to maintain
      physiologically active leaves for a greater fraction of the growing season than
      black grama potentially amplifies and extends the importance of physiological
      differences. These physiological and phenological differences may help account
      for grass displacement by shrubs in drylands. Furthermore, the greater
      sensitivity of the grass to low soil moisture suggests that grasslands may be
      increasingly susceptible to shrub encroachment in the face of the predicted
      increases in drought intensity and frequency in the desert of the southwestern
      USA.

PMID- 22159871
TI  - Contrasted effects of an oxidative challenge and alpha-melanocyte-stimulating
      hormone on cellular immune responsiveness: an experiment with red-legged
      partridges Alectoris rufa.
AB  - Oxidative stress is increasingly recognized as a key selective force shaping
      evolutionary trade-offs. One such trade-off involves investing in immunity versus
      combating oxidative stress. While there is broad evidence that mounting an immune
      response causes increased oxidative stress, the effect that increased oxidative
      stress during development has at a later stage on immune responsiveness remains
      little known. The production of melanin-based coloration in vertebrates is
      influenced by oxidative stress and by hormones, such as the alpha-melanocyte
      stimulating hormone (alpha-MSH). Oxidative stress could impair immunity, and this
      might be a cost associated with the production of melanin traits. alpha-MSH has
      immunomodulatory effects, with most evidence pointing towards an improvement of
      immunity (improved pro-inflammatory activity). Here, we investigated the effects
      of an oxidative challenge (exposure to a pro-oxidant compound, diquat) and of
      experimentally elevated alpha-MSH on the cell-mediated immune responses (CMIR) of
      growing young (1 month old) red-legged partridges Alectoris rufa in captivity.
      CMIR were assessed in response to primary and secondary challenges with
      phytohemagglutinin (PHA). We specifically tested whether an oxidative challenge
      during growth and development had a delayed effect (4 months after exposure) on
      immunity. We found that the diquat treatment did not affect primary CMIR, but
      significantly reduced secondary CMIR. Elevated alpha-MSH increased primary CMIR
      in males, but not in females. Our experimental results are consistent with a
      trade-off between investing in activities that generate oxidative stress (e.g.,
      growth, reproduction, production of ornaments) versus investing in immunity, and
      shed new lights onto the inter-relationships between immunity, oxidative stress
      and the expression of melanin-based coloration in vertebrates, revealing a novel,
      delayed physiological cost that can contribute to ensuring honest signaling.

PMID- 22159872
TI  - p53 codon 72 polymorphisms and random amplified polymorphic DNA analysis of non
      melanoma skin cancer through archival formalin-fixed paraffin-embedded tissue.
AB  - Non-melanoma skin cancer (NMSC) is classified among the ten most frequent cancers
      in Malaysia. A common polymorphism at codon 72 of the p53 tumor suppressor gene
      and its influence on cancer risk has been studied for different types of cancer
      with mixed and inconsistent results with limited published data on the Malaysian
      population so far. In the present study, the frequency of p53 codon 72
      polymorphism in 60 patients with NMSC was investigated from archival formalin
      fixed paraffin-embedded (FFPE) tissue obtained from Hospital Universiti
      Kebangsaan Malaysia (HUKM). Additionally, random amplified polymorhic DNA 
      polymorphic chain reaction (RAPD-PCR) was employed for preliminary biomarker
      development. NMSC FFPE samples (70%) possess Arg/Arg, 20% with Pro/Pro and 10%
      with Arg/Pro. In total, there was no significant difference in the p53 codon 72
      genotypes between histological types of NMSC, gender, race, tumor location and
      age group. However, there was an apparent age-associated increase in the Arg/Arg
      genotype but did not reach statistical significance (P=0.235). NMSC types and
      demographic characteristics did not influence genotype distribution. On the other
      hand, BCC and SCC distributions are influenced by age group, race and tumor
      location.

PMID- 22159873
TI  - TraML--a standard format for exchange of selected reaction monitoring transition
      lists.
AB  - Targeted proteomics via selected reaction monitoring is a powerful mass
      spectrometric technique affording higher dynamic range, increased specificity and
      lower limits of detection than other shotgun mass spectrometry methods when
      applied to proteome analyses. However, it involves selective measurement of
      predetermined analytes, which requires more preparation in the form of selecting
      appropriate signatures for the proteins and peptides that are to be targeted.
      There is a growing number of software programs and resources for selecting
      optimal transitions and the instrument settings used for the detection and
      quantification of the targeted peptides, but the exchange of this information is
      hindered by a lack of a standard format. We have developed a new standardized
      format, called TraML, for encoding transition lists and associated metadata. In
      addition to introducing the TraML format, we demonstrate several implementations
      across the community, and provide semantic validators, extensive documentation,
      and multiple example instances to demonstrate correctly written documents.
      Widespread use of TraML will facilitate the exchange of transitions, reduce time
      spent handling incompatible list formats, increase the reusability of previously
      optimized transitions, and thus accelerate the widespread adoption of targeted
      proteomics via selected reaction monitoring.

PMID- 22159875
TI  - CD70: probably being a therapeutic target in human multiple sclerosis.

PMID- 22159874
TI  - Neb: a zebrafish model of nemaline myopathy due to nebulin mutation.
AB  - Nemaline myopathy is one of the most common and severe non-dystrophic muscle
      diseases of childhood. Patients typically present in infancy with hypotonia,
      weakness, delayed motor development, and bulbar and respiratory difficulties.
      Mutations in six different genes are associated with nemaline myopathy, with
      nebulin mutations being the most common. No treatments or disease-modifying
      therapies have been identified for this disease. One of the major barriers to
      treatment development is the lack of models amenable to rapid and coordinated
      testing of potential therapeutic strategies. To overcome this barrier, we have
      characterized the first zebrafish model of nemaline myopathy. This model, termed
      neb, harbors a recessive mutation in the nebulin gene that results in decreased
      Nebulin protein levels, a severe motor phenotype and premature lethality. In
      addition to impaired motor function, neb zebrafish exhibit many of the features
      associated with human nemaline myopathy. These include impaired force generation,
      altered thin filament length and the presence of specific histopathological
      changes, including the formation of nemaline bodies. In summary, neb zebrafish
      mirror the genetic, clinical and pathological aspects of nemaline myopathy due to
      NEB mutation, and thus are an excellent model for future therapy development for
      this devastating disorder.

PMID- 22159876
TI  - Renal vein lengthening using gonadal vein reduces surgical difficulty in living
      donor kidney transplantation.

PMID- 22159879
TI  - Remifentanil use for cesarean section in a patient with intracranial re-ruptured
      arteriovenous malformation.
AB  - We describe the successful administration of remifentanil as part of the
      anesthetic technique used for cesarean section performed under general anesthesia
      in a 24-year-old woman with intracranial re-hemorrhage caused by re-ruptured
      arteriovenous malformation. A low dose of remifentanil was useful to obtund the
      hypertensive response during induction and maintenance of anesthesia without
      neonatal respiratory depression.

PMID- 22159881
TI  - Total spinal block after spinal anesthesia following ongoing epidural analgesia
      for cesarean delivery.

PMID- 22159882
TI  - Difficult tracheal intubation using the Airway Scope in a patient with unexpected
      mouth-opening difficulty.

PMID- 22159880
TI  - Caudal bupivacaine supplemented with morphine or clonidine, or supplemented with
      morphine plus clonidine in children undergoing infra-umbilical urological and
      genital procedures: a prospective, randomized and double-blind study.
AB  - PURPOSE: We aimed to evaluate postoperative analgesia of morphine, or clonidine,
      or morphine plus clonidine, added to caudal bupivacaine in children undergoing
      infra-umbilical urological and genital procedures. METHODS: Eighty patients aged
      1-10 years were prospectively enrolled. After the induction of general
      anesthesia, the patients were randomized to four caudal anesthesia groups: Group
      B (1.0 mL/kg of bupivacaine 0.166% with epinephrine 1:600,000); Group BM (1.0
      mL/kg of bupivacaine 0.166% with epinephrine 1:600,000 plus morphine 20 MUg/kg);
      Group BC (bupivacaine 0.166% with epinephrine 1:600,000 plus clonidine 1.0
      MUg/kg), and Group BMC (bupivacaine 0.166% with epinephrine 1:600,000 plus
      morphine 20 MUg/kg and clonidine 1.0 MUg/kg). Duration of surgery, emergence
      time, postoperative pain score measured by the face, legs, activity, cry,
      consolability (FLACC) scale, postoperative analgesia time, and overall use of
      rescue analgesics were recorded. RESULTS: The FLACC pain score (6, 12, and 24 h
      after the surgery) and the number of patients requiring analgesics during the
      first 24 h of the postoperative period were higher in Groups B and BC than in
      Groups BM and BMC (p < 0.05). The incidence of pruritus and urinary retention was
      comparable between the groups (p > 0.05). However, the incidence of postoperative
      nausea and vomiting (PONV) was higher in Groups BM (35%) and BMC (25%) than in
      Groups B (5%) and BC (5%) (p < 0.05). CONCLUSION: To conclude, we showed that 20
      MUg/kg of morphine added to caudal bupivacaine 0.166% plus epinephrine 1:600,000
      decreased the use of analgesics in the postoperative period, although it was
      associated with an increased incidence of PONV. However, the addition of
      clonidine (1.0 MUg/kg) to caudal bupivacaine provided no additional clinical
      benefit over bupivacaine alone.

PMID- 22159883
TI  - Bilateral aplasia of paranasal sinuses.
AB  - Paranasal sinus anatomical anomalies with unknown etiology are common. Maxillary
      and/or frontal sinus aplasia or hypoplasia are more common than the other types.
      Although there are some reports about paranasal sinus anomalies in the
      literature, there is no case similar to ours, with total paranasal sinus aplasia.
      Here, we present a unique case of total paranasal sinus aplasia with a symptom of
      fullness on the face.

PMID- 22159884
TI  - Increased metabolic rate and insulin sensitivity in male mice lacking the carcino
      embryonic antigen-related cell adhesion molecule 2.
AB  - AIMS/HYPOTHESIS: The carcino-embryonic antigen-related cell adhesion molecule
      (CEACAM)2 is produced in many feeding control centres in the brain, but not in
      peripheral insulin-targeted tissues. Global Ceacam2 null mutation causes insulin
      resistance and obesity resulting from hyperphagia and hypometabolism in female
      Ceacam2 homozygous null mutant mice (Cc2 [also known as Ceacam2](-/-)) mice.
      Because male mice are not obese, the current study examined their metabolic
      phenotype. METHODS: The phenotype of male Cc2(-/-) mice was characterised by body
      fat composition, indirect calorimetry, hyperinsulinaemic-euglycaemic clamp
      analysis and direct recording of sympathetic nerve activity. RESULTS: Despite
      hyperphagia, total fat mass was reduced, owing to the hypermetabolic state in
      male Cc2(-/-) mice. In contrast to females, male mice also exhibited insulin
      sensitivity with elevated beta-oxidation in skeletal muscle, which is likely to
      offset the effects of increased food intake. Males and females had increased
      brown adipogenesis. However, only males had increased activation of sympathetic
      tone regulation of adipose tissue and increased spontaneous activity. The
      mechanisms underlying sexual dimorphism in energy balance with the loss of
      Ceacam2 remain unknown. CONCLUSIONS/INTERPRETATION: These studies identified a
      novel role for CEACAM2 in the regulation of metabolic rate and insulin
      sensitivity via effects on brown adipogenesis, sympathetic nervous outflow to
      brown adipose tissue, spontaneous activity and energy expenditure in skeletal
      muscle.

PMID- 22159885
TI  - Polyphasic approach for the characterization of rhizobial symbionts effective in
      fixing N(2) with common bean (Phaseolus vulgaris L.).
AB  - Common bean (Phaseolus vulgaris L.) is a legume that has been reported as highly
      promiscuous in nodulating with a variety of rhizobial strains, often with low
      effectiveness in fixing nitrogen. The aim of this work was to assess the
      symbiotic efficiency of rhizobial strains isolated from common bean seeds,
      nodules of Arachis hypogaea, Mucuna pruriens, and soils from various Brazilian
      agroecosystems, followed by the characterization of elite strains identified in
      the first screening. Forty-five elite strains were analyzed for symbiotic
      properties (nodulation, plant-growth, and nitrogen-fixation parameters) under
      greenhouse conditions in pots containing non-sterile soil, and variation in
      symbiotic performance was observed. Elite strains were also characterized in
      relation to morpho-physiological properties, genetic profiles of rep-polymerase
      chain reaction (PCR; BOX), and restriction fragment length polymorphism (RFLP)
      PCR of the 16S rRNA. Sequence analyses of the 16S rRNA were obtained for 17
      strains representative of the main groups resulting from all previous analyses.
      One of the most effective strains, IPR-Pv 2604, was clustered with Rhizobium
      tropici, whereas strain IPR-Pv 583, showing lower effectiveness in fixing N(2),
      was clustered with Herbaspirillum lusitanum. Surprisingly, effective strains were
      clustered with unusual symbiotic genera/species, including Leifsonia xyli,
      Stenotrophomonas maltophilia, Burkholderia, and Enterobacter. Some strains
      recognized in this study were outstanding in their nitrogen-fixing capacity and
      therefore, show high biotechnological potential for use in commercial inoculants.

PMID- 22159886
TI  - Synthesis and characterization of the antibacterial potential of ZnO
      nanoparticles against extended-spectrum beta-lactamases-producing Escherichia
      coli and Klebsiella pneumoniae isolated from a tertiary care hospital of North
      India.
AB  - The reemergence of infectious diseases and the continuous development of
      multidrug resistance among a variety of disease-causing bacteria in clinical
      setting pose a serious threat to public health worldwide. Extended-spectrum beta
      lactamases (ESBLs) that mediate resistance to third-generation cephalosporin are
      now observed all over the world in all species of Enterobacteriaceae, especially
      Escherichia coli and Klebsiella pneumoniae. In this work, ZnO nanoparticles (NPs)
      were synthesized by the sol-gel method and characterized by powder X-ray
      diffraction, scanning electron microscopy (SEM) and atomic force microscopy
      (AFM). The image of synthesized ZnO NPs appeared spherical in SEM with a diameter
      of ~19 nm and as hexagonal crystal in AFM. Clinical isolates were assessed for
      ESBL production and shown to be sensitive to ZnO NPs by different methods such as
      minimal inhibitory concentration (MIC) and minimal bactericidal concentration,
      time-dependent growth inhibition assay, well diffusion agar methods and
      estimation of colony forming units (CFU) of bacteria. The lowest MIC value for E.
      coli and K. pneumoniae was found to be 500 MUg/ml. The results showed that ZnO
      NPs at 1,000 MUg/ml completely inhibit the bacterial growth. The antibacterial
      effect of ZnO nanoparticles was gradual, but time- and concentration-dependent.
      The maximum inhibition zone at100 MUg/ml for E. coli and K. pneumoniae was 22 and
      20 mm, respectively. With the increasing ZnO NP loading, there is significant
      reduction in the numbers of CFU. At the concentration of 1,000 MUg/ml, the
      decline in per cent survival of E. coli and K. pneumoniae was found to be 99.3%
      and 98.6%, respectively.

PMID- 22159887
TI  - Beneficial effects of Lactobacillus paracasei subsp. paracasei NTU 101 and its
      fermented products.
AB  - It is well-known that probiotics have a number of beneficial health effects in
      humans and animals, including the reduction of symptoms in lactose intolerance
      and enhancement of the bioavailability of nutrients. Probiotics have showed to
      possess antimutagenic, anticarcinogenic and hypocholesterolemic properties.
      Further, they were also observed to have antagonistic actions against intestinal
      and food-borne pathogens, to decrease the prevalence of allergies in susceptible
      individuals and to have immunomodulatory effects. Typically, the bacteria
      colonise the intestinal tract first and then reinforce the host defence systems
      by inducing a generalised mucosal immune response, balanced T-helper cell
      response, self-limited inflammatory response and secretion of polymeric IgA.
      Scientific reports showed that the Taiwan native lactic acid bacterium from
      newborn infant faeces identified as Lactobacillus paracasei subsp. paracasei NTU
      101 and its fermented products proved to be effective for the management of blood
      cholesterol and pressure, prevention of gastric mucosal lesion development,
      immunomodulation and alleviation of allergies, anti-osteoporosis and inhibition
      the fat tissue accumulation. This review article describes that the beneficial
      effects of this Lactobacillus strains and derivative products may be suitable for
      human and animals.

PMID- 22159888
TI  - CHO cells in biotechnology for production of recombinant proteins: current state
      and further potential.
AB  - Recombinant Chinese hamster ovary cells (rCHO) cells have been the most commonly
      used mammalian host for large-scale commercial production of therapeutic
      proteins. Recent advances in cell culture technology for rCHO cells have achieved
      significant improvement in protein production leading to titer of more than 10
      g/L to meet the huge demand from market needs. This achievement is associated
      with progression in the establishment of high and stable producer and the
      optimization of culture process including media development. In this review
      article, we focus on current strategies and achievements in cell line
      development, mainly in vector engineering and cell engineering, for high and
      stable protein production in rCHO cells. The approaches that manipulate various
      DNA elements for gene targeting by site-specific integration and cis-acting
      elements to augment and stabilize gene expression are reviewed here. The genetic
      modulation strategy by "direct" cell engineering with growth-promoting and/or
      productivity-enhancing factors and omics-based approaches involved in
      transcriptomics, proteomics, and metabolomics to pursue cell engineering are also
      presented.

PMID- 22159889
TI  - Long-term field fertilization alters the diversity of autotrophic bacteria based
      on the ribulose-1,5-biphosphate carboxylase/oxygenase (RubisCO) large-subunit
      genes in paddy soil.
AB  - Carbon dioxide (CO(2)) assimilation by autotrophic bacteria is an important
      process in the soil carbon cycle with major environmental implications. The long
      term impact of fertilizer on CO(2) assimilation in the bacterial community of
      paddy soils remains poorly understood. To narrow this knowledge gap, the
      composition and abundance of CO(2)-assimilating bacteria were investigated using
      terminal restriction fragment length polymorphism and quantitative PCR of the
      cbbL gene [that encodes ribulose-1,5-biphosphate carboxylase/oxygenase (RubisCO)]
      in paddy soils. Soils from three stations in subtropical China were used. Each
      station is part of a long-term fertilization experiment with three treatments: no
      fertilizer (CK), chemical fertilizers (NPK), and NPK combined with rice straw
      (NPKM). At all of the stations, the cbbL-containing bacterial communities were
      dominated by facultative autotrophic bacteria such as Rhodopseudomonas palustris,
      Bradyrhizobium japonicum, and Ralstonia eutropha. The community composition in
      the fertilized soil (NPK and NPKM) was distinct from that in unfertilized soil
      (CK). The bacterial cbbL abundance (3-8 * 10(8) copies g soil(-1)) and RubisCO
      activity (0.40-1.76 nmol CO(2) g soil(-1) min(-1)) in paddy soils were
      significantly positively correlated, and both increased with the addition of
      fertilizer. Among the measured soil parameters, soil organic carbon and pH were
      the most significant factors influencing the community composition, abundance,
      and activity of the cbbL-containing bacteria. These results suggest that long
      term fertilization has a strong impact on the activity and community of cbbL
      containing bacterial populations in paddy soils, especially when straw is
      combined with chemical fertilizers.

PMID- 22159890
TI  - Construction of new Pichia pastoris X-33 strains for production of lycopene and
      beta-carotene.
AB  - In this study, we used the non-carotenogenic yeast Pichia pastoris X33 as a
      receptor for beta-carotene-encoding genes, in order to obtain new recombinant
      strains capable of producing different carotenoidic compounds. We designed and
      constructed two plasmids, pGAPZA-EBI* and pGAPZA-EBI*L*, containing the genes
      encoding lycopene and beta-carotene, respectively. Plasmid pGAPZA-EBI*, expresses
      three genes, crtE, crtB, and crtI*, that encode three carotenogenic enzymes,
      geranylgeranyl diphosphate synthase, phytoene synthase, and phytoene desaturase,
      respectively. The other plasmid, pGAPZA-EBI*L*, carried not only the three genes
      above mentioned, but also the crtL* gene, that encodes lycopene beta-cyclase. The
      genes crtE, crtB, and crtI were obtained from Erwinia uredovora, whereas crtL*
      was cloned from Ficus carica (JF279547). The plasmids were integrated into P.
      pastoris genomic DNA, and the resulting clones Pp-EBI and Pp-EBIL were selected
      for either lycopene or beta-carotene production and purification, respectively.
      Cells of these strains were investigated for their carotenoid contents in YPD
      media. These carotenoids produced by the recombinant P. pastoris clones were
      qualitatively and quantitatively analyzed by high-resolution liquid
      chromatography, coupled to photodiode array detector. These analyses confirmed
      that the recombinant P. pastoris clones indeed produced either lycopene or beta
      carotene, according to the integrated vector, and productions of 1.141 MUg of
      lycopene and 339 MUg of beta-carotene per gram of cells (dry weight) were
      achieved. To the best of our knowledge, this is the first time that P. pastoris
      has been genetically manipulated to produce beta-carotene, thus providing an
      alternative source for large-scale biosynthesis of carotenoids.

PMID- 22159891
TI  - Chemically inhibited ATP synthesis promoted detachment of different-age biofilms
      from membrane surface.
AB  - This study investigated the response of different-age biofilms developed on
      membrane surface to a chemical uncoupler 3, 3', 4', 5-tetrachlorosalicylanilide
      (TCS). Results showed that adenosine triphosphate (ATP) dissipation caused by TCS
      would promote different-age biofilms detachment, whereas chemically inhibited
      cellular ATP synthesis subsequently suppressed autoinducer-2 (AI-2) and
      extracellular polymeric substances (EPS) production. The extent of biofilm
      detachment was found to be closely related to AI-2-regulated EPS contents of
      bacteria. It was revealed that energy dissipation induced biofilm detachability
      was controlled by AI-2 regulated cellular communication via AI-2-mediated EPS
      secretion. This study would lead to a new cleaning strategy of biologically
      fouled membrane.

PMID- 22159892
TI  - Evolution and some functions of the NprR-NprRB quorum-sensing system in the
      Bacillus cereus group.
AB  - Quorum-sensing (QS) is a bacterial mechanism for regulation of gene expression in
      response to cell density. In Gram-positive bacteria, oligopeptides are the
      signaling molecules to elicit QS. The RNPP protein family (Rap, NprR, PlcR, and
      PrgX) are intracellular QS receptors that bind directly to their specific
      signaling peptide for regulating the transcription of several genes. NprR is the
      activator of a neutral protease in Bacillus subtilis, and it has been recently
      related to sporulation, cry genes transcription and extracellular protease
      activity in strains from the B. cereus group. In the B. thuringiensis genome,
      downstream nprR, a gene encoding a putative QS signaling propeptide (nprRB) was
      found. We hypothesized that the nprR and nprRB co-evolved because of their
      coordinated function in the B. cereus group. A phylogenetic tree of nucleotide
      sequences of nprR revealed six pherotypes, each corresponding to one putative
      mature NprRB sequence. The nprR tree does not match the current taxonomic
      grouping of the B. cereus group or the phylogenetic arrangement obtained when
      using MLST markers from the same strains. SKPDI and other synthetic peptides
      encoded in the nprRB gene from B. thuringiensis serovar thuringiensis strain 8741
      had effect on temporal regulation of sporulation and expression of a cry1Aa'Z
      transcriptional fusion, but those peptides that stimulated earlier detection of
      spores decreased cry1Aa expression suggesting that NprR may either activate or
      repress the transcription of different genes.

PMID- 22159893
TI  - Phenylboronic acid functionalized gold nanoparticles for highly sensitive
      detection of Staphylococcus aureus.
AB  - Herein, we report a phenylboronic acid functionalized gold nanoparticle (GNP)
      based colorimetric assay for rapid detection of Staphylococcus aureus (S. aureus)
      with high sensitivity. In this approach, GNPs can bind to S. aureus by the
      reaction of phenylboronic acid with the cis-diol configuration in glycans on the
      bacterial surface, providing a colorimetric readout of the binding event. Using
      this strategy, we have been able to quantify S. aureus at a concentration of 50
      cells per mL (three times the standard deviation divided by the slope of the
      working curve) in aqueous solution.

PMID- 22159894
TI  - In vitro anti-neuroblastoma activity of saquinavir and its association with
      imatinib.
AB  - Neuroblastoma (NB) has a poor prognosis when in advanced stages, highlighting the
      need for new therapeutic options. The human immunodeficiency virus (HIV) protease
      inhibitor saquinavir is active in vitro against chronic myeloid leukaemia cells,
      in synergy with the tyrosine kinase inhibitor imatinib. Here, we evaluated the
      effects of saquinavir, alone or in association with imatinib, on cell
      proliferation (count of viable cells after trypan blue exclusion), apoptosis
      (Annexin V binding) and invasion (through a transwell membrane coated with
      Matrigel) in SJ-N-KP, IMR5, AF-8, SK-N-SH and SK-N-BE NB lines, all expressing c
      kit and PDGF-R (determined by flow cytometry). Saquinavir showed a dose-dependent
      anti-proliferative and anti-invasive activity on NB lines, increased by the
      association with imatinib when the two drugs were utilized at clinically
      attainable concentrations. The same low saquinavir concentrations inhibited in NB
      cells the nuclear activation of NF-kappaB (Western immuno-blotting for nuclear NF
      kappaB p50 and p65). Saquinavir at high concentrations also exerted a pro
      apoptotic activity on NB lines, significantly increased by the association with
      imatinib. In conclusion, saquinavir and imatinib are both drugs utilized for long
      term therapies, with good oral bioavailability and a well-known toxicity profile.
      The anti-NB activity of saquinavir and of its association with imatinib suggests
      a potential usefulness in the treatment of NB, particularly for remission
      maintenance.

PMID- 22159895
TI  - Sustained risk of recurrent thromboembolic events in patients with patent foramen
      ovale and paradoxical embolism: long-term follow-up over more than 15 years.
AB  - BACKGROUND: Patients with patent foramen ovale (PFO) and cryptogenic stroke are
      at risk of recurrence. Therapeutic regimens range from no treatment to
      anticoagulation treatment to surgical or interventional closure. However, long
      term follow-up is only available for up to 4 years. METHODS: Among ~5,000
      transesophageal echocardiographies in stroke/TIA-patients between 1988 and 1997,
      a PFO was found and considered a possible mediator for the neurological event in
      97 patients. In these patients, the PFO was judged to be responsible for the
      neurological event. Patients with cardiac or other reasons for embolism were
      excluded. The therapy for stroke was chosen by the attending physician. Follow-up
      information was obtained through telephone interviews. RESULTS: Follow-up was
      available for 86 patients (89%) with a mean period of 15.4 years (range, 11.2
      25.9 years). Thirteen patients (15%) suffered from recurrent ischemic events (7
      TIAs, 5 strokes, 1 peripheral embolism) after a mean period of 4.9 years. Four
      patients died, not associated with recurrent thromboembolism. The risk of
      recurrence was increased over the entire length of the mean follow-up period. The
      occurrence of recurrent events was not associated with differences in baseline
      data, the presence of ASA, PFO size or the chosen treatment. CONCLUSION: In
      patients with paradoxical embolism, recurrent ischemic events are frequent
      despite medical therapy. These events are not limited to the early years after
      the index event; this long-term follow-up revealed a risk of occurrence over the
      entire follow-up. These patients have a sustained risk of recurrence, requiring
      lifetime protection, which should be considered in tailoring individual
      therapeutic strategies.

PMID- 22159896
TI  - Morphological and phenological shoot plasticity in a Mediterranean evergreen oak
      facing long-term increased drought.
AB  - Mediterranean trees must adjust their canopy leaf area to the unpredictable
      timing and severity of summer drought. The impact of increased drought on the
      canopy dynamics of the evergreen Quercus ilex was studied by measuring shoot
      growth, leaf production, litterfall, leafing phenology and leaf demography in a
      mature forest stand submitted to partial throughfall exclusion for 7 years. The
      leaf area index rapidly declined in the throughfall-exclusion plot and was 19%
      lower than in the control plot after 7 years of treatment. Consequently, leaf
      litterfall was significantly lower in the dry treatment. Such a decline in leaf
      area occurred through a change in branch allometry with a decreased number of
      ramifications produced and a reduction of the leaf area supported per unit
      sapwood area of the shoot (LA/SA). The leafing phenology was slightly delayed and
      the median leaf life span was slightly longer in the dry treatment. The canopy
      dynamics in both treatments were driven by water availability with a 1-year lag:
      leaf shedding and production were reduced following dry years; in contrast, leaf
      turnover was increased following wet years. The drought-induced decrease in leaf
      area, resulting from both plasticity in shoot development and slower leaf
      turnover, appeared to be a hydraulic adjustment to limit canopy transpiration and
      maintain leaf-specific hydraulic conductivity under drier conditions.

PMID- 22159897
TI  - Differences in metabolite burden of di(2-ethylhexyl)phthalate in pregnant and
      postpartum dams and their offspring in relation to drug-metabolizing enzymes in
      mice.
AB  - Di(2-ethylhexyl)phthalate (DEHP) induced adverse effects on mice offspring, and
      the metabolite mono(2-ethylhexyl)phthalate (MEHP) may be essential to determine
      the toxicity. In this experiment, we measured liver MEHP levels and the factors
      determining the metabolism, two enzyme activities [lipase and uridine 5'
      diphosphate-glucuronosyltransferase (UGT)] or expression of cytochrome P450 4A14
      (CYP4A14) in dams (on gestational day 18 and postnatal day 2) and their
      offspring. MEHP concentrations in the liver from pregnant dams were 1.5 times
      higher than those of postpartum dams at exposure to 0.05% DEHP. Accordingly, MEHP
      concentrations were 1.7 times higher in fetuses than in pups at the dose.
      Interestingly, lipase activity was 1.8-fold higher in pregnant dams than
      postpartum ones, but no such difference was noted in the activity between fetuses
      and pups. UGT activity was also 1.5-fold higher in pregnant dams than postpartum
      ones, whereas the activity in the fetuses was 1/2 that of pups. No difference was
      noted in CYP4A14 levels between pregnant and postpartum mice, whereas the levels
      in the fetuses were <1/10 those of pups. DEHP exposure did not influence lipase
      activity, whereas it slightly enhanced UGT activity and exclusively increased
      CYP4A14 levels in pregnant and/or postpartum dams. Taken together, the higher
      MEHP levels in pregnant dams than postpartum ones may be primarily due to higher
      lipase activities in pregnant dams, which may closely reflect those in fetuses
      and pups.

PMID- 22159898
TI  - Mechanism of ziram-induced apoptosis in human T lymphocytes.
AB  - Ziram as a dithiocarbamate fungicide is widely used throughout the world in
      agriculture. We previously found that ziram significantly inhibited cytotoxic T
      lymphocyte activity in a dose-dependent manner. To explore the mechanism of this
      inhibition, we investigated ziram-induced apoptosis in human T lymphocytes.
      Jurkat T cells were treated with ziram at 0.031-1 MUM for 2-24 h. Freshly
      isolated primary human T cells were treated with ziram at 0.0625-1 MUM for 15 and
      24 h. Apoptosis was determined by FITC-Annexin V/PI staining and the TUNEL assay.
      To explore the mechanism of apoptosis, intracellular levels of active caspases 3,
      3/7, 8, and 9 and pan-caspase and mitochondrial cytochrome-c release were
      determined by flow cytometry. Disruption to mitochondrial transmembrane potential
      was determined with a MitoLight(TM) Apoptosis Detection Kit. We found that ziram
      induced apoptosis in a time- and dose-dependent manner in both Jurkat cells and
      primary human T cells. The primary human T cells were more sensitive to ziram
      than the Jurkat cell line. Ziram induced increases in active caspases 3, 3/7, 8,
      and 9 and pan-caspase in a dose-dependent manner, and a caspase-3 inhibitor, Z
      DEVD-FMK, partially but significantly inhibited the apoptosis. Moreover, a
      general caspase inhibitor, Z-VAD-FMK, significantly and almost completely blocked
      the apoptosis. Ziram also disrupted mitochondrial transmembrane potential and
      caused mitochondrial cytochrome-c release. These findings indicate that ziram can
      induce apoptosis in human T cells, and the apoptosis is mediated by both the
      caspase-cascade and the mitochondria/cytochrome-c pathways.

PMID- 22159899
TI  - The novel function of Oct3/4 in mouse tooth development.
AB  - Octamer-binding factor 3/4 (Oct3/4) is one of the key regulators maintaining the
      pluripotency and self-renewal in embryonic stem cells and is involved in the
      developmental events. However, the functional significance of Oct3/4 remains to
      be clarified during tooth morphogenesis. This study aimed to examine the
      functional role of Oct3/4 in mouse. During tooth morphogenesis (E11-E16.5),
      Oct3/4-positive cells, detected by nuclear immunoreaction, increased in number,
      and subsequently, their immunoreaction shifted from the nucleus to the cytoplasm
      at the stage of cell differentiation (E18.5). Quantitative real-time PCR clearly
      demonstrated the relationship between isoforms of Oct3/4 and the in vivo cellular
      localization of Oct3/4, suggesting that the Oct3/4 expressed in nucleus was
      Oct3/4A, whereas that expressed in the cytoplasm was Oct3/4B. RNAi knockdown of
      Oct3/4 induced apoptosis and arrested tooth morphogenesis. Our results suggest
      that (1) the increased number of Oct3/4-positive cells with nuclear
      immunoreaction correlate with active cell proliferation during tooth
      morphogenesis and (2) the shift of Oct3/4 from the nucleus to the cytoplasm plays
      a crucial role in cell differentiation.

PMID- 22159901
TI  - Transient atrial fibrillation complicating acute myocardial infarction: a
      nuisance or a nemesis?

PMID- 22159900
TI  - Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor
      immune response in an immunocompetent murine model of human prostate cancer.
AB  - Advanced castration-resistant prostate cancer has high mortality rates and
      limited treatment options. Novel therapies are needed to better contend with this
      disease. Polysaccharide-K(r) (PSK), an extract of the mushroom Trametes
      versicolor, has immunomodulatory and tumor suppressive activities. PSK is used in
      Asia as a cancer immunotherapy. However, its benefit in combination with taxanes
      for prostate cancer is unknown. We examined whether PSK would enhance docetaxel
      induced apoptosis and augment anti-tumor immune responses in orthotopic tumors
      using transgenic adenocarcinoma of the mouse prostate (TRAMP)-C2-bearing mice.
      Combining PSK with docetaxel induced significantly higher tumor suppression than
      either treatment alone (p<0.05), including a reduction in tumor proliferation and
      enhanced apoptosis. Combined PSK and docetaxel treatment led to a lower decrease
      in number of white blood cells than docetaxel alone, an effect accompanied by
      increased numbers of tumor-infiltrating CD4+ and CD8+ T cells. PSK with or
      without docetaxel significantly enhanced mRNA expression of IFN-gamma compared to
      control, but did not significantly alter T-regulatory FoxP3 mRNA expression in
      tumors. PSK also augmented docetaxel-induced splenic natural killer cell
      cytolytic activity against YAC-1 target cells (p=0.045). This study is the first
      to show that PSK enhances docetaxel-induced prostate cancer tumor suppression,
      apoptosis and antitumor responses.

PMID- 22159902
TI  - Fixing simple olecranon fractures with the Olecranon Osteotomy Nail (OleON).
AB  - OBJECTIVE: Stable fixation of simple olecranon fractures or olecranon osteotomies
      in order to allow early functional treatment. INDICATIONS: Simple (non
      comminuted) olecranon fractures and (Chevron) osteotomies of the olecranon.
      CONTRAINDICATIONS: Comminuted fractures and fractures more than 40 mm distal than
      the tip of the olecranon are contraindications. SURGICAL TECHNIQUE: Using a
      slightly curved posterior approach, the fracture is anatomically reduced. The
      fracture is temporary stabilized using K-wires. A guiding K-wire is positioned
      centrally in the medullary canal in the lateral projection. The medullary canal
      is reamed over the K-wire. The distal part of the nail is inserted and locked.
      The proximal part is inserted and screwed onto the distal part to compress the
      fracture. For osteotomies, the distal part is inserted and locked (using the same
      technique as described before) prior to performing the osteotomy. At the end of
      the surgery, the osteotomy is reduced, the proximal part is inserted, and the
      osteotomy is compressed. POSTOPERATIVE MANAGEMENT: As the stability of this
      compressive osteosynthesis is very high, early post-operative mobilization is
      allowed. No immobilization is used. Depending on the soft tissue situation,
      active range of motion and passive stretching is initiated immediately
      postoperatively. RESULTS: Using this technique in 21 patients (mean age 42 years)
      with acute fractures or osteotomies, sound fracture healing was achieved in 19 of
      21 patients. The active range of motion was 130.2 degrees  flexion, 10.6 degrees 
      extension deficit, and a normal pro-supination arch. In one patient, delayed
      union caused implant failure. In this patient, a surgical error jeopardized
      stability. In a second patient, a peri-implant fracture after adequate trauma
      made a change in therapy necessary.

PMID- 22159903
TI  - Insights into electrocatalysis.
AB  - When standard reversible potentials for bulk solution reactions, U(0), are known,
      the reversible potentials when the reactant and product are adsorbed on an
      electrocatalyst surface, U(surf)(rev), are given in terms of these potentials and
      the adsorption Gibbs energy bond strengths: U(surf)(rev) = U0 + D(ads)G (Ox)/F
      Delta(ads)G (R)/F (i). When the Delta(ads)G (Ox) and Delta(ads)G (Red) values are
      known at potential U, this equation is exact. When the overpotential for a multi
      electron transfer reaction is minimal, each electron transfer takes place at the
      standard reversible potential for the overall reaction. In the case of O(2)
      reduction to water via the intermediate step OOH(aq) -> O(aq) + OH(aq), or via
      O(2)(g) -> 2O(aq), the respective endergonic O-O dissociation Gibbs energies are
      shown to be 2.52 eV and 4.76 eV. When the oxygen product and water reactant
      adsorb weakly, as on platinum, the adsorption Gibbs energies, Delta(ads)G, for O,
      OH, and OOH intermediates can be uniquely predicted using these data. All of the
      above depend exclusively on experimentally determined data. Reversible potentials
      have been calculated for oxygen reduction steps on the platinum electrocatalyst
      surface using Interface 1.0, a comprehensive computational code for the potential
      dependence of the electrochemical interface. Using these results as benchmarks,
      is found to be accurate to around 0.1 V when the Delta(ads)G are values
      calculated for the potentials of zero charge, instead of 1.229 V, which is a
      significant simplification. The variation in Delta(ads)G values between the
      calculated potentials of zero charge and 1.229 V are found to be 0.2 eV V(-1) or
      less. Prior work, using internal adsorption energies calculated at the potential
      of zero charge in place of Gibbs energies in was found to be accurate to within
      about 0.2 V. On platinum Delta(ads)G of the reaction OOH(ads) -> O(ads) + OH(ads)
      is calculated at the potential of zero charge for the reactant and product to be
      about 1.2 eV exergonic under Langmuir conditions, and this Gibbs energy loss
      reduces the 1.229 V four-electron reversible potential on the platinum surface to
      an effective reversible potential of about 0.93 V for this mechanism on platinum.
      The effective reversible potential is a consequence of efficiency loss, not
      kinetics. Based on these values, the onset potential for four-electron oxygen
      reduction will be less than or equal to the effective reversible potential and on
      pure Pt(111) it appears to be equal to it.

PMID- 22159904
TI  - Coronary artery lesions of incomplete Kawasaki disease: a nationwide survey in
      Japan.
AB  - Incomplete Kawasaki disease (KD) is associated with delayed diagnosis and
      treatment, which in turn can lead to the development of coronary artery lesions
      (CALs). The aim of this study was to determine the epidemiological features of
      incomplete KD compared with complete KD and to identify risk factors for CALs
      from incomplete KD patients using data from a nationwide survey of 2007-2008 in
      Japan. A total of 23,263 patients were classified according to the number of
      principal clinical signs: 80% (n = 18,620) had complete forms of KD, 14.2% had
      four principal signs, 4.6% had three signs, and 1.2% had only one or two signs.
      In comparison with complete KD cases, the prevalence of CAL development tended to
      be larger and the proportion receiving initial intravenous immunoglobulin (IVIG)
      treatment were significantly smaller in patients with incomplete forms. In
      addition, hospital attendance after 7 days of illness or later was significantly
      associated with CAL development in all incomplete groups (OR: 2.52 in total
      patients with incomplete KD, 3.26 in those with one or two principal signs, 2.94
      in those with three signs, 2.35 in those with four signs). CONCLUSION: The higher
      prevalence of CALs in incomplete KD reflects difficulties in diagnosis and delays
      in treatment. More timely diagnosis and treatment of incomplete KD patients could
      further prevent the development of cardiac lesions.

PMID- 22159905
TI  - Two cases of type A infant botulism in Grenoble, France: no honey for infants.
AB  - We report two severe cases of infant botulism diagnosed at Grenoble University
      Hospital, France, respectively in 2006 and 2009. Both cases were characterized by
      a delay in diagnosis, severe neurological manifestations and extended period of
      hospitalization in intensive care unit, but a complete recovery. Infant botulism
      is a rare but life-threatening disease. It primarily affects infants, and the
      main risk factor is honey ingestion. Diagnosis should be systematically evoked by
      pediatricians in infants suffering from constipation, fatigue, muscle weakness,
      difficult feeding and altered cry, but before the onset of generalized flaccid
      paralysis, so as to administer specific treatment (BabyBIG(r), a human derived
      botulinum antitoxin) at an early stage of the disease when it is most effective.
      In conclusion, parents should be aware of the role of honey as a source of spores
      of Clostridium botulinum and therefore infant botulism in the first year of life.

PMID- 22159906
TI  - A systematic review of protocols for the three-dimensional morphologic assessment
      of abdominal aortic aneurysms using computed tomographic angiography.
AB  - The morphology of infrarenal abdominal aortic aneurysms (AAAs) directly
      influences the perioperative outcome and long-term durability of endovascular
      aneurysm repair. A variety of methods have been proposed for the characterization
      of AAA morphology using reconstructed three-dimensional (3D) computed tomography
      (CT) images. At present, there is lack of consensus as to which of these methods
      is most applicable to clinical practice or research. The purpose of this review
      was to evaluate existing protocols that used 3D CT images in the assessment of
      various aspects of AAA morphology. An electronic search was performed, from
      January 1996 to the end of October 2010, using the Embase and Medline databases.
      The literature review conformed to PRISMA statement standards. The literature
      search identified 604 articles, of which 31 studies met inclusion criteria. Only
      15 of 31 studies objectively assessed reproducibility. Existing published
      protocols were insufficient to define a single evidence-based methodology for
      preoperative assessment of AAA morphology. Further development and expert
      consensus are required to establish a standardized and validated protocol to
      determine precisely how morphology relates to outcomes after endovascular
      aneurysm repair.

PMID- 22159907
TI  - Percutaneous transsplenic access to the portal vein for management of vascular
      complication in patients with chronic liver disease.
AB  - PURPOSE: To evaluate the safety and feasibility of percutaneous transsplenic
      access to the portal vein for management of vascular complication in patients
      with chronic liver diseases. METHODS: Between Sept 2009 and April 2011,
      percutaneous transsplenic access to the portal vein was attempted in nine
      patients with chronic liver disease. Splenic vein puncture was performed under
      ultrasonographic guidance with a Chiba needle, followed by introduction of a 4 to
      9F sheath. Four patients with hematemesis or hematochezia underwent variceal
      embolization. Another two patients underwent portosystemic shunt embolization in
      order to improve portal venous blood flow. Portal vein recanalization was
      attempted in three patients with a transplanted liver. The percutaneous
      transsplenic access site was closed using coils and glue. RESULTS: Percutaneous
      transsplenic splenic vein catheterization was performed successfully in all
      patients. Gastric or jejunal varix embolization with glue and lipiodol mixture
      was performed successfully in four patients. In two patients with a massive
      portosystemic shunt, embolization of the shunting vessel with a vascular plug,
      microcoils, glue, and lipiodol mixture was achieved successfully. Portal vein
      recanalization was attempted in three patients with a transplanted liver;
      however, only one patient was treated successfully. Complete closure of the
      percutaneous transsplenic tract was achieved using coils and glue without
      bleeding complication in all patients. CONCLUSION: Percutaneous transsplenic
      access to the portal vein can be an alternative route for portography and further
      endovascular management in patients for whom conventional approaches are
      difficult or impossible.

PMID- 22159908
TI  - Uteroenteric fistula resulting from fibroid expulsion after uterine fibroid
      embolization: case report and review of the literature.
AB  - A 44-year-old woman underwent uncomplicated uterine fibroid embolization (UFE)
      for menstrual and bulk-related symptoms in an enlarged, myomatous uterus. After
      surgery, she spontaneously sloughed a large mass of fibroids that arrested in the
      cervical canal during passage. Four days after gynecological extraction, she
      developed copious vaginal discharge that contained enteric contents. Contrast
      enhanced computed tomography (CT) demonstrated a fistula between the small bowel
      and the uterus. She subsequently underwent hysterectomy, left oophorectomy, and
      small-bowel resection. Her postoperative recovery was uneventful.

PMID- 22159909
TI  - Decreased neointimal extracellular matrix formation in RAGE-knockout mice after
      microvascular denudation.
AB  - PURPOSE: To evaluate in vivo the role of RAGE (receptor for advanced glycated end
      products) in the development of restenosis and neointimal proliferation in RAGE
      deficient knockout (KO) mice compared with wild-type (WT) mice in an animal
      model. MATERIALS AND METHODS: Sixteen WT and 15 RAGE-deficient mice underwent
      microvascular denudation of the common femoral artery under general anaesthesia.
      Contralateral arteries underwent a sham operation and served as controls. Four
      weeks after the intervention, all animals were killed, and paraformaldehyde-fixed
      specimens of the femoral artery were analysed with different stains (hematoxylin
      and eosin and Elastica van Gieson) and several different types of immunostaining
      (proliferating cell nuclear antigen, alpha-actin, collagen, von Willebrand
      factor, RAGE). Luminal area, area of the neointima, and area of the media were
      measured in all specimens. In addition, colony-formation assays were performed,
      and collagen production by WT smooth muscle cells (SMCs) and RAGE-KO SMCs was
      determined. For statistical analysis, P < 0.05 was considered statistically
      significant. RESULTS: Four weeks after denudation, WT mice showed a 49.6% loss of
      luminal area compared with 14.9% loss of luminal area in RAGE-deficient mice
      (sham = 0% loss) (P < 0.001). The neointima was 18.2 (*1000 MUm(2) [n = 15) in
      the WT group compared with only 8.4 (*1000 MUm(2) [n = 16]) in the RAGE-KO group.
      RAGE-KO SMCs showed significantly decreased proliferation activity and production
      of extracellular matrix protein. CONCLUSION: RAGE may be shown to play a
      considerable role in the formation of neointima leading to restenosis after
      vascular injury.

PMID- 22159910
TI  - B-type natriuretic peptide (BNP) affects the initial response to intravenous
      glucose: a randomised placebo-controlled cross-over study in healthy men.
AB  - AIMS/HYPOTHESIS: B-type natriuretic peptide (BNP) is a hormone released from
      cardiomyocytes in response to cell stretching and elevated in heart failure.
      Recent observations indicate a distinct connection between chronic heart failure
      and diabetes mellitus. This study investigated the role of BNP on glucose
      metabolism. METHODS: Ten healthy volunteers (25 +/- 1 years; BMI 23 +/- 1
      kg/m(2); fasting glucose 4.6 +/- 0.1 mmol/l) were recruited to a participant
      blinded investigator-open placebo-controlled cross-over study, performed at a
      university medical centre. They were randomly assigned (sequentially numbered
      opaque sealed envelopes) to receive either placebo or 3 pmol kg(-1) min(-1) BNP
      32 intravenously during 4 h on study day 1 or 2. One hour after beginning the
      BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose
      + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C
      peptide were frequently measured. RESULTS: Ten volunteers per group were
      analysed. BNP increased the initial glucose distribution volume (13 +/- 1% body
      weight vs 11 +/- 1%, p < 0.002), leading to an overall reduction in glucose
      concentration (p < 0.001), particularly during the initial 20 min of the test (p
      = 0.001), accompanied by a reduction in the initial C-peptide levels (1.42 +/-
      0.13 vs 1.62 +/- 0.10 nmol/l, p = 0.015). BNP had no impact on beta cell
      function, insulin clearance or insulin sensitivity and induced no adverse
      effects. CONCLUSIONS/INTERPRETATION: Intravenous administration of BNP increases
      glucose initial distribution volume and lowers plasma glucose concentrations
      following a glucose load, without affecting beta cell function or insulin
      sensitivity. These data support the theory that BNP has no diabetogenic
      properties, but improves metabolic status in men, and suggest new questions
      regarding BNP-induced differences in glucose availability and signalling in
      various organs/tissues. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01324739
      FUNDING: The study was funded by Jubilee Fonds of the Austrian National Bank
      (OeNB-Fonds).

PMID- 22159911
TI  - Fatty acids acutely enhance insulin-induced oxidative stress and cause insulin
      resistance by increasing mitochondrial reactive oxygen species (ROS) generation
      and nuclear factor-kappaB inhibitor (IkappaB)-nuclear factor-kappaB (NFkappaB)
      activation in rat muscle, in the absence of mitochondrial dysfunction.
AB  - AIMS/HYPOTHESIS: Insulin effects reportedly involve reactive oxygen species (ROS)
      and oxidative stress in vitro, but skeletal muscle oxidative stress is an
      emerging negative regulator of insulin action following high-fat feeding. NEFA
      may enhance oxidative stress and insulin resistance. We investigated the acute
      impact of insulin with or without NEFA elevation on muscle ROS generation and
      insulin signalling, and the potential association with altered muscle
      mitochondrial function. METHODS: We used hyperinsulinaemic-euglycaemic clamping,
      150 min, without or with lipid infusion to modulate plasma NEFA concentration in
      lean rats. RESULTS: Insulin and glucose (Ins) infusion selectively enhanced
      xanthine oxidase-dependent muscle ROS generation. Ins with lipid infusion
      (Ins+NEFA) lowered whole-body glucose disposal and muscle insulin signalling, and
      these effects were associated with high muscle mitochondrial ROS generation and
      activation of the proinflammatory nuclear factor-kappaB inhibitor (IkappaB)
      nuclear factor-kappaB (NFkappaB) pathway. Antioxidant infusion prevented NEFA
      induced systemic insulin resistance and changes in muscle mitochondrial ROS
      generation, IkappaB-NFkappaB pathway and insulin signalling. Changes in insulin
      sensitivity and signalling were independent of changes in mitochondrial enzyme
      activity and ATP production, which, in turn, were not impaired by changes in ROS
      generation under any condition. CONCLUSIONS/INTERPRETATION: Acute muscle insulin
      effects include enhanced ROS generation through xanthine oxidase. Additional NEFA
      elevation enhances mitochondrial ROS generation, activates IkappaB-NFkappaB and
      reduces insulin signalling. These alterations are not associated with acute
      reductions in mitochondrial enzyme activity and ATP production, and are reversed
      by antioxidant infusion. Thus, NEFA acutely cause systemic and muscle insulin
      resistance by enhancing muscle oxidative stress through mitochondrial ROS
      generation and IkappaB-NFkappaB activation.

PMID- 22159912
TI  - Involvement of the RNA-binding protein ARE/poly(U)-binding factor 1 (AUF1) in the
      cytotoxic effects of proinflammatory cytokines on pancreatic beta cells.
AB  - AIMS/HYPOTHESIS: Chronic exposure of pancreatic beta cells to proinflammatory
      cytokines leads to impaired insulin secretion and apoptosis. ARE/poly(U)-binding
      factor 1 (AUF1) belongs to a protein family that controls mRNA stability and
      translation by associating with adenosine- and uridine-rich regions of target
      messengers. We investigated the involvement of AUF1 in cytokine-induced beta cell
      dysfunction. METHODS: Production and subcellular distribution of AUF1 isoforms
      were analysed by western blotting. To test for their role in the control of beta
      cell functions, each isoform was overproduced individually in insulin-secreting
      cells. The contribution to cytokine-mediated beta cell dysfunction was evaluated
      by preventing the production of AUF1 isoforms by RNA interference. The effect of
      AUF1 on the production of potential targets was assessed by western blotting.
      RESULTS: MIN6 cells and human pancreatic islets were found to produce four AUF1
      isoforms (p42>p45>p37>p40). AUF1 isoforms were mainly localised in the nucleus
      but were partially translocated to the cytoplasm upon exposure of beta cells to
      cytokines and activation of the ERK pathway. Overproduction of AUF1 did not
      affect glucose-induced insulin secretion but promoted apoptosis. This effect was
      associated with a decrease in the production of the anti-apoptotic proteins, B
      cell leukaemia/lymphoma 2 (BCL2) and myeloid cell leukaemia sequence 1 (MCL1).
      Silencing of AUF1 isoforms restored the levels of the anti-apoptotic proteins,
      attenuated the activation of the nuclear factor-kappaB (NFkappaB) pathway, and
      protected the beta cells from cytokine-induced apoptosis.
      CONCLUSIONS/INTERPRETATION: Our findings point to a contribution of AUF1 to the
      deleterious effects of cytokines on beta cell functions and suggest a role for
      this RNA-binding protein in the early phases of type 1 diabetes.

PMID- 22159914
TI  - Addition of a video camera system improves the ease of Airtraq((r)) tracheal
      intubation during chest compression.
AB  - Recent resuscitation guidelines for cardiopulmonary resuscitation emphasize that
      rescuers should perform tracheal intubation with minimal interruption of chest
      compressions. We evaluated the use of video guidance to facilitate tracheal
      intubation with the Airtraq (ATQ) laryngoscope during chest compression. Eighteen
      novice physicians in our anesthesia department performed tracheal intubation on a
      manikin using the ATQ with a video camera system (ATQ-V) or with no video
      guidance (ATQ-N) during chest compression. All participants were able to intubate
      the manikin using the ATQ-N without chest compression, but five failed during
      chest compression (P < 0.05). In contrast, all participants successfully secured
      the airway with the ATQ-V, with or without chest compression. Concurrent chest
      compression increased the time required for intubation with the ATQ-N (without
      chest compression 14.8 +/- 4.5 s; with chest compression, 28.2 +/- 10.6 s; P <
      0.05), but not with the ATQ-V (without chest compression, 15.9 +/- 5.8 s; with
      chest compression, 17.3 +/- 5.3 s; P > 0.05). The ATQ video camera system
      improves the ease of tracheal intubation during chest compressions.

PMID- 22159913
TI  - Preclinical efficacy of sodium narcistatin to reduce inflammation and joint
      destruction in rats with adjuvant-induced arthritis.
AB  - Current therapies for the treatment of rheumatoid arthritis (RA) do not work for
      all patients, can lose efficacy over time, and can have significant side effects.
      The discovery of new, effective therapies for RA remains an unmet medical need.
      The Amaryllidaceae isocarbostyril narciclasine was previously shown to
      prophylactically reduce paw swelling in rats with adjuvant-induced arthritis
      (AA). In this study, the efficacy of sodium narcistatin (SNS), a water-soluble
      cyclic phosphate pro-drug of narciclasine, was assessed in AA rats for anti
      inflammatory and bone-sparing properties after disease onset. AA rats were given
      daily intraperitoneal injections of SNS (1.75, 3.5, or 5 mg/kg/day, in 500 MUl
      sterile endotoxin-free saline) or saline from disease onset through severe
      disease stages. Footpad widths and radiographic scoring were used as indicators
      of inflammation and joint destruction, respectively. Ex vivo cytokine production
      by peripheral blood mononuclear cells (PMBC), splenocytes, and draining lymph
      node (DLN) cells were determined using ELISAs. SNS treatment dose-dependently
      reduced joint inflammation (~70%) and bone loss (~50%) compared with AA controls.
      SNS treatment also reduced spleen weight (without affecting body weight), pro
      inflammatory cytokine production by PMBC, splenocytes, and DLN cells, and site
      dependently altered T-helper (Th)1-/Th2-type and anti-inflammatory cytokine
      profiles. SNS dramatically reduces inflammation and has bone-sparing properties,
      possibly by reducing immune cell pro-inflammatory cytokine production. Our
      findings support the development of SNS as a therapeutic for RA.

PMID- 22159915
TI  - Objective measurement of real time subglottic pressure during medialization
      thyroplasty: a feasibility study.
AB  - It is hypothesized that real time objective measurement of the subglottic
      pressure could contribute to the choice of the implant's size (IS) in
      medialization thyroplasty (MT). A prospective study was conducted with patients
      with glottal insufficiency. Patients had a MT using a Montgomery implant((r))
      (Boston medical, Boston, USA). Peak direct subglottic pressure (PDSGP) was
      measured intraoperatively using a catheter inserted in the cricothyroid membrane.
      The implant's choice was based on the results of PDSGP measured prior and after
      placement of the implant and was compared to the surgeon's and patient's
      perception and fiber optic estimation of the glottis aperture. Six patients were
      included in the first part of the study. The PDSGP could be measured in all the
      patients without increasing the surgical time or patients' discomfort. The mean
      PDSGP before and after the placement of the implant was 15.2 (SD = 5) and 10.6
      (SD = 4) cmH(2)O, respectively. In the second part of the study, five patients
      were included. The PDSGP varied with the size of the implant and the implant with
      the lowest pressure was chosen in 4/5 patients. Peroperative measurement of PDSGP
      is easy, feasible and might allow a more objective choice of the IS in MT. Level
      of evidence 2c.

PMID- 22159916
TI  - Cochlear implantation outcomes in children with Waardenburg syndrome.
AB  - Waardenburg syndrome (WS) is an autosomal dominant disease, characterized by
      dystopia canthorum, hyperplasia of the eyebrows, heterochromia iridis, white
      forelock, and congenital sensori-neural hearing loss (SNHL). The aim of this
      study was to evaluate the outcome of cochlear implantation in children with WS
      and compare it with children with pure SNHL. In a prospective study we evaluated
      336 cochlear implanted children from 2008 to 2010. The WS was diagnosed by its
      established criteria and for control group children without any dysmorphic
      features, anatomical, behavioral, and developmental disorders were also enrolled.
      We evaluated children of both groups 1 year after cochlear implantation by
      categories of auditory performance (CAP) and speech intelligibility rating (SIR)
      tests. Eighty-one children out of the total 336 who had SNHL were included in
      study. Out of these 75 (22.3%) were healthy and six (1.78%) had WS. Of the 75
      healthy children 40 (53.3%) were girls, while of the six children with WS, three
      (50%) were girls. There was a significant difference in SIR between WS and cases
      with pure SNHL (2.67 +/- 1.03 vs. 3.79 +/- 1.11, p = 021) however, the difference
      was not significant in CAP (4 +/- 1.26 vs. 5.13 +/- 1.13, p = 0.082). Prevalence
      of WS was 1.78% at Baqiyatallah Cochlear Implant Center. One year after
      implantation there was no significant difference in auditory outcome; however,
      the difference in speech outcome was significant between WS and cases with pure
      SNHL.

PMID- 22159917
TI  - Water-soluble, deep-red fluorescent squaraine rotaxanes.
AB  - Eight fluorescent squaraine rotaxanes with deep-red absorption/emission
      wavelengths were prepared and assessed for chemical stability and suitability as
      water-soluble, fluorescent tracers. The most stable squaraine rotaxanes have four
      large stopper groups attached to the ends of the encapsulated squaraine, and two
      members of this structural class have promise as highly fluorescent tracers with
      rapid renal clearance and very low tissue uptake in living mice.

PMID- 22159918
TI  - Non-interactive multiple predator effects on tadpole survival.
AB  - Interactions among and within three species of predators were estimated in terms
      of their effects on prey survival using short-term predation experiments. The
      prey were tadpoles (Rana temporaria), and the predators were dragonfly larvae
      (Anax imperator), newts (Triturus alpestris), and backswimmers (Notonecta
      glauca). Mortality rate per predator imposed by Triturus and Notonecta did not
      decline with predator density, whereas the predation rate of Anax was strongly
      reduced when the number of predator individuals increased. Impacts of all three
      predators were not altered by the presence of other species in pairwise
      combinations. This system is therefore characterized by interference between
      individual dragonflies but relatively independent effects of predator species.
      These results were largely predictable based on the natural history of the
      predators and are encouraging for attempts to model communities as assemblages of
      interacting species.

PMID- 22159919
TI  - Sources of variation in plant responses to belowground insect herbivory: a meta
      analysis.
AB  - Growing interest in belowground herbivory and the remarkable diversity of the
      accumulated information on this topic inspired us to quantitatively explore the
      variation in the outcomes of individual studies. We conducted a meta-analysis of
      85 experimental studies reporting the effects of root-feeding insect herbivores
      (36 species) on plants (75 species). On average, belowground herbivory led to a
      36.3% loss of root biomass, which was accompanied by a reduction in aboveground
      growth (-16.3%), photosynthesis (-11.7%) and reproduction (-15.5%). The effects
      of root herbivory on aboveground plant characteristics were significant in
      agricultural and biological control studies, but not in studies of natural
      systems. Experiments conducted in controlled environments yielded larger effects
      on plants than field experiments, and infestation experiments resulted in more
      severe effects than removal studies employing natural levels of herbivory.
      Simulated root herbivory led to greater aboveground growth reductions than
      similar root loss imposed by insect feeding. External root chewers caused
      stronger detrimental effects than sap feeders or root borers; specialist
      herbivores imposed milder adverse effects on plants than generalists. Woody
      plants suffered from root herbivory more than herbaceous plants, although root
      loss was similar in these two groups. Evergreen woody plants responded to root
      herbivory more strongly than deciduous woody plants, and grasses suffered from
      root herbivory more than herbs. Environmental factors such as drought, poor
      nutrient supply, among-plant competition, and aboveground herbivory increased the
      adverse effects of root damage on plants in an additive manner. In general, plant
      tolerance to root herbivores is lower than tolerance to defoliating aboveground
      herbivores.

PMID- 22159920
TI  - A MRI classification of periprosthetic soft tissue masses (pseudotumours)
      associated with metal-on-metal resurfacing hip arthroplasty.
AB  - OBJECTIVE: Metal-on-metal hip resurfacing arthroplasty (MoMHRA) has become a
      popular option for young patients requiring hip replacement. A recognised
      complication is the formation of a symptomatic reactive periprosthetic soft
      tissue mass (pseudotumour). We present a radiological classification system for
      these reactive masses, dividing them into three groups: Type I are thin-walled
      cystic masses (cyst wall <3 mm), Type II are thick-walled cystic masses (cyst
      wall >3 mm, but less than the diameter of the cystic component) and Type III are
      predominantly solid masses. MATERIALS AND METHODS: We reviewed all MRI performed
      over a 4-year period in patients with primary MoMHRA referred to our institution.
      In all cases the masses were assessed on MRI according to size, anatomical
      position, signal intensity and involvement of bone, muscle or neighbouring
      neurovascular bundles. RESULTS: Periprosthetic masses were seen in 33 hips in 17
      female (7 bilateral) and 8 male patients (1 bilateral). The Type I lesions were
      the most common and more likely to be posterior to the hip joint. The Type III
      masses were significantly larger than the cystic lesions and were more likely to
      be located anterior to the hip joint. To date 22 patients have undergone revision
      surgery with conversions to total hip replacement. Severity of symptoms and
      revision rates were lowest in the Type I group and highest in the Type III group.
      CONCLUSION: Solid anterior pseudotumours were most likely to have the more severe
      symptoms and require revision surgery.

PMID- 22159922
TI  - On the methodology and scientific fundamentals of organizing, representing and
      analysing data, information and knowledge in biomedicine and health care.
AB  - This issue of  Methods of Information in Medicine  celebrates the journal's first
      50 years. As the oldest journal in biomedical and health informatics and, being
      broader in its scope, as the journal dealing with the methodology and scientific
      fundamentals of organizing, representing and analysing data, information and
      knowledge in biomedicine and health care, the journal publications during the
      last five decades also reflect the formation of a scientific field that deals
      with information in biomedicine and health care. Five papers that arose from a
      scientific symposium on "biomedical informatics: confluence of multiple
      disciplines" held in Heidelberg, Germany, in June 2011 are included in this
      volume. The papers reflect not only the broad interdisciplinary scope of the
      journal, but also the broad and evolving scope of the field itself. We can also
      recognise that there is an ongoing need for original and relevant research. As a
      discipline that has an impact on many other fields and is also influenced by
      them, scientific exchange and collaborative research continues to be needed.

PMID- 22159921
TI  - The involvement of FoxO in cell survival and chemosensitivity mediated by
      Mirk/Dyrk1B in ovarian cancer.
AB  - Minibrain-related kinase (Mirk) is a serine/threonine kinase which is also known
      as the dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B). It
      is known that Dyrk1A, the closest family member to Mirk/Dyrk1B can mediate
      cellular localization of mammalian forkhead subclass O (FoxO1), a transcription
      factor, although the effect of Mirk/Dyrk1B on FoxO factors remains to be defined.
      In this study, we showed that Mirk/Dyrk1B protein was overexpressed in 5 of 8
      ovarian cancer cell lines and negatively correlated with the protein level of
      FoxO factors (FoxO1+FoxO3A). Knockdown of Mirk by small interfering RNA (siRNA)
      resulted in cell apoptosis and sensitized cells to cisplatin accompanied by
      nuclear translocation of FoxO1 and/or FoxO3A as well as increased Bim, TRADD,
      cleaved caspase-3 and PARP. Furthermore, combined siRNAs of Mirk with FoxO1
      and/or FoxO3A led to fewer apoptotic cells and cisplatin sensitivity compared to
      Mirk siRNA alone, suggesting that FoxO is involved in Mirk-mediated cell survival
      and chemosensitivity of ovarian cancer. Taken together, Mirk/Dyrk1B plays an
      important role in ovarian cancer cell survival through modulating FoxO
      translocation and may be a novel therapeutic target for ovarian cancer.

PMID- 22159923
TI  - Biological monitoring of carcinogens: current status and perspectives.
AB  - Biomonitoring exposures to carcinogens is common practice and a variety of
      biomarkers have been developed to assess both exposures and
      biochemical/biological effects. However, their clinical and preventive relevance
      is still uncertain. The understanding of cancer as a genetic disease has
      dramatically evolved during last decades, showing that cancer cell types acquire
      their characteristics with different strategies, time frames and
      microenvironments. Therefore, the place of current biomarkers within this complex
      scenario of gene-environment interactions leading to cancer cannot be defined.
      Reasons are manifold. Most studies assessed cancer risk on a group basis through
      snapshots taken at unknown time-points of the postulated chain of events. Little
      attention has been paid to the variety and variability of exposures, and no
      prospective study validated the indicators of biochemical/biological effects. New
      opportunities and suggestions for biomonitoring exposures to carcinogens could
      derive from exploring the exposome that combines exposures from all sources both
      external and internal. The discovery of new biomarkers and the identification of
      relevant gene-specific pathways could be achieved through metabolomic and genome
      wide studies. In conclusion, it is possible to envisage personalized
      biomonitoring procedures, such as those already implemented in the context of
      nutrition and clinical oncology.

PMID- 22159925
TI  - Electrocardiography Series. ECGs of structural heart disease: Part 1.
AB  - Electrocardiogram (ECG) is a useful but imperfect investigation in the diagnosis
      and possible follow-up of structural heart disease such as ventricular
      hypertrophy. Different ECG criteria with different sensitivity and specificity
      are available to aid the detection of left or right ventricular hypertrophy.
      Subsequent echocardiography can help in the quantification of ventricular mass
      and identification of the aetiology.

PMID- 22159924
TI  - A weight-of-evidence review of colorectal cancer in pesticide applicators: the
      agricultural health study and other epidemiologic studies.
AB  - OBJECTIVE: To systematically evaluate epidemiologic studies on pesticides and
      colon cancer and rectal cancer in agricultural pesticide applicator populations
      using a transparent "weight-of-evidence" (WOE) methodological approach. METHODS:
      Twenty-nine (29) publications from the Agricultural Health Study (AHS) and 13
      additional epidemiologic studies were identified that reported data for pesticide
      applicators and/or specific pesticide compounds and colorectal, colon, or rectal
      cancer. The AHS evaluated pesticide applicators as well as dose-response
      associations for specific pesticide compounds, whereas the large majority of non
      AHS evaluated applicators but did not analyze specific compounds or dose-response
      trends. This WOE assessment of 153 different pesticide-outcome pairs emphasized
      several key evidentiary features: existence of statistically significant relative
      risks, magnitude of observed associations, results from the most reliable
      exposure assessments, and evidence of convincing dose-response relationships
      (i.e., those monotonically increasing, with statistically significant trend
      tests). RESULTS: Occupation as a pesticide applicator or pesticide application as
      a farming-related function was not associated with increasing the risk of colon
      or rectal cancer. Deficits of colon or rectal cancer were observed across most
      studies of pesticide applicators. After applying the WOE methodology to the
      epidemiologic studies of specific pesticide compounds and colon or rectal cancer,
      a number of pesticide-outcome pairs were identified and evaluated further based
      on positive statistical associations. Of these, only two-aldicarb and colon
      cancer and imazethapyr and proximal colon cancer-appears to warrant further
      discussion regarding a possible causal relationship, although the epidemiologic
      data are limited. For the remainder, a lack of a clear dose-response trend,
      inconsistencies in associations between exposure metrics and comparison groups,
      imprecise associations, variable participation rates for analyses of specific
      compounds, and the reliance upon data from one study (the AHS) limit
      interpretation regarding risk. CONCLUSION: The available epidemiologic evidence
      does not support a causal relationship between occupation as a pesticide
      applicator or specific pesticide exposures and colon or rectal cancer.

PMID- 22159926
TI  - Acute HIV infection in Singapore: predominance of men who have sex with men.
AB  - INTRODUCTION: The incidence of human immunodeficiency virus (HIV) infection in
      Singapore is on the rise. We aimed to study the clinical epidemiology of acute
      HIV infection in Singapore. METHODS: All patients that fulfilled the criteria for
      definite and probable acute HIV infection were prospectively identified from
      January 1, 2003 to June 30, 2006. Demographic, clinical and laboratory data were
      recorded. RESULTS: A total of 16 out of 34 patients had definite acute HIV
      infection, and 68 percent of the entire cohort comprised men who have sex with
      men (MSM). Ten percent of the patients were co-infected with hepatitis B and C
      viruses, while 27 percent were infected with syphilis. Signs and symptoms were
      nonspecific, with fever, rash and diarrhoea being the three most common symptoms.
      Only 35 percent of the patients required hospitalisation. CONCLUSION: Men who
      have sex with men account for the majority of patients with acute HIV infections
      in Singapore, many of them also being co-infected with syphilis. Safer sex
      campaign among MSM should be implemented or intensified.

PMID- 22159927
TI  - Markers of genital tuberculosis in infertility.
AB  - INTRODUCTION: Although genital tuberculosis is a condition that is prevalent
      worldwide, it is still a diagnostic dilemma. This study aimed to find an
      effective diagnostic modality for the condition. METHODS: A total of 100
      infertile women were clinically evaluated with haemoglobin estimation, total and
      differential count, Mantoux test, tubercle bacilli enzyme-linked immunosorbent
      assay (TB ELISA), hysterosalpingography, pelvic ultrasonography,
      laparohysteroscopy, premenstrual endometrial biopsy for histopathology, culture
      and tubercle bacilli polymerase chain reaction (TBPCR). The womens' Day 2
      hormonal profile (luteinising, follicle-stimulating, prolactin and
      thyroidstimulating hormones) and their husbands' semen analysis were also
      conducted. RESULTS: A total of 58 women had primary infertility and 42 had
      secondary infertility. Female factor infertility was present in 63 percent of the
      cases (mostly tubal; 45.97 percent). 26 women tested positive for endometrial
      TBPCR. Erythrocyte sedimentation rate, Mantoux test, TB ELISA and
      hysterosalpingography were found to have high negative predictive value (greater
      than 80 percent), while the positive predictive value was 35-45 percent.
      Laparoscopy findings were suggestive of tuberculosis in 13 percent of the women,
      out of which 83.3 percent were positive for endometrial TBPCR. Hysteroscopy
      revealed intrauterine adhesions in 34.8 percent of the women, with 68.8 percent
      being positive for tubercular bacilli. CONCLUSION: Our study established that in
      cases of genital tuberculosis, the use of expensive endometrial TBPCR tests may
      be avoided with a detailed workup, which would also help in the institution of
      anti-tubercular treatment in early disease, thus enhancing the chance of
      pregnancy.

PMID- 22159928
TI  - The efficacy and safety of intramuscular injections of methylcobalamin in
      patients with chronic nonspecific low back pain: a randomised controlled trial.
AB  - INTRODUCTION: Chronic, nonspecific low back pain is a difficult ailment to treat
      and poses an economic burden in terms of medical expenses and productivity loss.
      The aim of this study was to determine the efficacy and safety of intramuscular
      metylcobalamin in the treatment of chronic nonspecific low back pain. METHODS:
      This was a double-blinded, randomised, controlled experimental study. 60 patients
      were assigned to either the methylcobalamin group or the placebo group. The
      former received intramuscular injections of 500 mcg parenteral methylcobalamin in
      1 ml solution three times a week for two weeks, and the placebo group received 1
      ml normal saline. Patients were assessed with Oswestry Disability Index
      questionnaire Version 2.0 and Visual Analogue Scale pain score. They were scored
      before commencement of the injections and at two months interval. RESULTS: Of the
      60 patients, 27 received the placebo injections and 33 were given methylcobalamin
      injections. A total of 58 patients were available for review at two months
      (placebo: n is 26; methylcobalamin: n is 32). There was a significant improvement
      in the Oswestry Disability Index and Visual Analogue Scale pain scores in the
      methylcobalamin group as compared with the placebo group (p-value less than
      0.05). Only minor adverse reactions such as pain and haematoma at the injection
      sites were reported by some patients. CONCLUSION: Intramuscular methylcobalamin
      is both an effective and safe method of treatment for patients with nonspecific
      low back pain, both singly or in combination with other forms of treatment.

PMID- 22159929
TI  - A randomised controlled study comparing the effects of laryngeal mask airway and
      endotracheal tube on early postoperative pulmonary functions.
AB  - INTRODUCTION: Classic laryngeal mask airway (LMA) has long been used for airway
      management. General anaesthesia has been associated with a significant decrease
      in pulmonary functions during the postoperative period. The decrease in pulmonary
      functions has been found to be greater with the use of a tracheal tube (TT). In
      this study, we compared the effects on pulmonary functions during the early
      postoperative period when the airway was managed using an LMA versus a TT.
      METHODS: A total of 20 patients in each group received either LMA or TT for
      airway management. Postoperative pulmonary functions were recorded at 30 and 60
      minutes after removal of the airway device in patients undergoing peripheral limb
      surgeries. Forced vital capacity (FVC) , forced expiratory volume during the
      first second (FEV1), vital capacity, FEV1/FVC, peak expiratory flow rate and
      percentage saturation of oxygenated haemoglobin were compared. Postoperative
      coughing and hoarseness were also recorded. RESULTS: Pulmonary functions were
      significantly decreased in both groups at 30 and 60 minutes postoperatively. The
      decrease in the TT group was significantly greater than that in the LMA group at
      both 30 and 60 minutes. The FEV1/ FVC was not significantly changed, indicating a
      restrictive pattern. Patients in the TT group had a significantly higher
      incidence of coughing at both 30 and 60 minutes. CONCLUSION: The use of LMA
      instead of TT for airway management during peripheral limb surgeries causes less
      depression of pulmonary functions during the early postoperative period. The
      incidence of coughing is also significantly lower.

PMID- 22159930
TI  - Effect of pre-emptive gabapentin on postoperative pain following lower extremity
      orthopaedic surgery under spinal anaesthesia.
AB  - INTRODUCTION: Gabapentin has demonstrated efficacy in clinical trials as a pre
      emptive analgesic and in acute postoperative pain management. However, our
      experience with the drug is still limited. The present study was conducted in
      order to evaluate the effect of gabapentin on reduction of postoperative pain in
      the first 24 hours after internal fixation of the tibia under spinal anaesthesia.
      METHODS: In a double-blind, randomised controlled clinical trial, 64 American
      Society of Anesthesiologists Class I or II patients, who underwent internal
      fixation of the tibia, were administered 300 mg of gabapentin or a placebo two
      hours before surgery. The postoperative pain was assessed using Visual Analogue
      Scale two, 12 and 24 hours after surgery. The time from the end of surgery until
      the first bolus dose of morphine on demand (pain score > 4) and the total
      morphine requirement were recorded. Patients were also asked about the possible
      side effects of gabapentin. RESULTS: The pain score was significantly lower in
      the gabapentin group at two hours post surgery (p-value is 0.004), while the
      scores at 12 and 24 hours post surgery were not significantly different between
      the two groups. No side effect of gabapentin was observed. CONCLUSION: Pre
      emptive use of gabapentin 300 mg orally significantly decreases postoperative
      pain two hours after surgery.

PMID- 22159931
TI  - Perioperative administration of gabapentin 1,200 mg day-1 and pregabalin 300 mg
      day-1 for pain following lumbar laminectomy and discectomy: a randomised, double
      blinded, placebo-controlled study.
AB  - INTRODUCTION: Gabapentin and pregabalin have been compared in studies conducted
      on management of neuropathic and postoperative pain. In neuropathic pain studies,
      the analgesic effects of the two drugs were compared, and pregabalin has been
      found to be more potent. However, in postoperative pain studies, the effects of
      each drug were examined separately. This study compared the analgesic effects of
      pregabalin (300 mg day-1), gabapentin (1,200 mg day-1) and a placebo in managing
      postoperative pain following laminectomy and discectomy. METHODS: 90 patients
      were randomly assigned to three groups (pregabalin, gabapentin and placebo) of 30
      patients each. Pregabalin 150 mg, gabapentin 600 mg and a placebo were
      administered every 12 hours, two times pre- and post surgery. Study data
      collected included morphine consumption, Visual Analogue Scale records,
      preoperative anxiety, patient satisfaction, adverse effects and observation
      notes. RESULTS: In the gabapentin and pregabalin groups, overall morphine
      consumption, preoperative anxiety, pruritus, postoperative shivering were
      significantly lower (p-value less than 0.05 for all), and patient satisfaction
      was significantly higher than those in the placebo group (p-value less than
      0.05). CONCLUSION: This study showed that both pregabalin 300 mg day-1 and
      gabapentin 1,200 mg day-1 have more analgesic, anxiolytic and opioid-sparing
      effects, higher patient satisfaction and are more effective for preventing
      postoperative shivering than the placebo following lumbar laminectomy and
      discectomy. The findings revealed that pregabalin 300 mg day-1 had equivalent
      analgesic, adverse and opioid-sparing effects and patient satisfaction as
      gabapentin 1,200 mg day-1.

PMID- 22159932
TI  - Changes in serum leptin and adiponectin concentrations and insulin resistance
      after curative parathyroidectomy in moderate to severe primary
      hyperparathyroidism.
AB  - INTRODUCTION: Primary hyperparathyroidism (PHPT) is considered a state of insulin
      resistance. However, it is unclear whether the state of insulin resistance and
      adverse levels of adipocytokines are reversed in PHPT patients who have undergone
      curative parathyroidectomy. METHODS: Ten consecutive patients with PHPT were
      studied at baseline and three months after curative parathyroid surgery in this
      prospective interventional study. Fasting blood calcium, intact parathyroid
      hormone (PTH), glucose, insulin, adiponectin and leptin concentrations were
      measured. Insulin resistance was assessed using the homeostasis model assessment
      of insulin resistance (HOMA- IR) and insulin sensitivity, by the quantitative
      insulin sensitivity check index (QUICKI). RESULTS: Four out of the ten patients
      were male. The mean age of the patients was 32.40 +/- 11.42 years, and the mean
      body mass index was 23.70 +/- 5.19 kg/m2. The HOMA-IR value was found to be
      higher, while the QUICKI value was significantly lower before surgery in patients
      with PHPT compared to the published reference ranges. Serum leptin concentrations
      were higher in patients with PHPT than in normal healthy individuals; however,
      there was no difference in the adiponectin concentrations. There was no
      statistical difference in the mean values of fasting plasma glucose, plasma
      insulin, leptin, adiponectin, as well as the HOMA-IR and QUICKI estimates three
      months postoperatively, as compared to the preoperative measures. CONCLUSION:
      Peripheral insulin resistance/sensitivity and the concentrations of leptin and
      adiponectin did not change three months after curative parathyroidectomy.

PMID- 22159933
TI  - Changes in the BODE index, exacerbation duration and hospitalisation in a cohort
      of COPD patients.
AB  - INTRODUCTION: We investigated the relationship between frequency of exacerbation
      and duration and change in functional status, as measured by the BODE index in
      chronic obstructive pulmonary disease (COPD) patients. METHODS: This was a
      longitudinal cohort study of 56 patients with moderate to severe COPD. Body mass
      index, spirometry, Modified Medical Research Council (MMRC) dyspnoea score and
      six-minute walk distance (6MWD) were measured annually when the patients were
      clinically stable. Data on frequency and duration of COPD exacerbations occurring
      in the community and requiring hospitalisation were collected prospectively.
      Early stage exacerbations were identified through the use of individualised
      patient action plans and further reinforced by fortnightly phone contact.
      RESULTS: At the two-year follow-up, the BODE index increased in 33 patients,
      remained stable in 18 and decreased in five patients. Patients with increased
      BODE index had significantly higher hospital presentation rates and longer total
      bed-days compared to those with stable BODE index. Among the 33 patients with
      increased BODE index, 20 had lower 6MWD and higher MMRC scores, indicating
      deteriorating functional status, and 13 had higher levels of airway obstruction.
      Between these two subgroups, patients with deteriorating functional status had
      higher exacerbation frequency, longer exacerbation duration and higher inpatient
      bed-days. Linear regression showed that total annual duration of exacerbation was
      predictive of change in 6MWD. CONCLUSION: Change in the BODE index is a sensitive
      measure of deteriorating functional status in COPD patients. Duration of
      exacerbation has greater impact on functional status than frequency of
      exacerbation episodes.

PMID- 22159934
TI  - The development of hyperbaric and diving medicine in Singapore.
AB  - Hyperbaric oxygen therapy is a noninvasive therapy used in the treatment of
      diving-related medical illnesses. It is an important adjunct in the management of
      a variety of medical conditions. The Republic of Singapore Navy Medical Service
      (NMS) is the main driver of the development of hyperbaric and diving medicine in
      Singapore. The practice of hyperbaric medicine has inherent risks, and
      unregulated application of this therapy may do more harm than good. NMS and
      Singapore General Hospital (SGH) signed a Memorandum of Understanding to combine
      NMS' experience with the clinical expertise of SGH to provide holistic care for
      diving and clinical hyperbaric treatment patients. This collaboration would
      increase the profile of this clinical specialty in Singapore, and help to
      establish safe clinical practice guidelines, training and accreditation
      requirements for diving and hyperbaric medicine practitioners in Singapore, thus
      ensuring that the practice of bona fide hyperbaric medicine is safeguarded and
      patient care is not compromised.

PMID- 22159935
TI  - Incidental cardiac abnormalities on non-electrocardiogram-gated multi-detector
      computed tomography imaging of the thorax and abdomen.
AB  - Little attention is usually paid to the heart on non-electrocardiogram (ECG)
      gated multi-detector computed tomography (MDCT) imaging of the thorax and
      abdomen. The current MDCT systems have fast scanning capabilities that render non
      ECG-gated images with reduced cardiac motion artefacts due to greater temporal
      and spatial resolution. This has allowed for better evaluation of the cardiac
      structures. We present a pictorial review of incidental cardiac abnormalities
      found on MDCT imaging of the thorax and abdomen performed in our institution. We
      systematically describe abnormalities involving the pericardium, myocardium,
      cardiac valves, cardiac chambers, coronary artery and congenital heart disease.
      Some of these images have echocardiograph and magnetic resonance imaging
      correlation. The purpose of this pictorial essay is to draw attention to cardiac
      abnormalities found incidentally on non-ECG-gated MDCT imaging of the thorax and
      abdomen, which may or may not be related to the patient's symptoms.

PMID- 22159936
TI  - Ministry of Health clinical practice guidelines: bipolar disorder.
AB  - The Ministry of Health (MOH) has published clinical practice guidelines on
      Bipolar Disorder to provide doctors and patients in Singapore with evidence-based
      guidance on the management of bipolar disorders. This article reproduces the
      introduction and executive summary (with recommendations from the guidelines)
      from the MOH clinical practice guidelines on Bipolar Disorder, for the
      information of readers of the Singapore Medical Journal. Chapters and page
      numbers mentioned in the reproduced extract refer to the full text of the
      guidelines, which are available from the Ministry of Health website: http:
      //www.moh.gov.sg/content/moh_web/home/Publications/guidelines/clinical_practicegu
      delines/2011/bipolar_disorder.html. The recommendations should be used with
      reference to the full text of the guidelines. Following this article are multiple
      choice questions based on the full text of the guidelines.

PMID- 22159937
TI  - Comment on: Aviation medicine: global historical perspectives and the development
      of aviation medicine alongside the growth of Singapore's aviation landscape.

PMID- 22159943
TI  - Management of choledochal cyst with portal hypertension.
AB  - Portal hypertension (PHT) is a rare complication associated with choledochal
      cysts. Management issues of PHT patients are inadequately addressed, as its
      incidence is low and underlying causes variable. We report three cases of
      choledochal cyst with PHT. All patients had type IVa choledochal cysts, and the
      causes of PHT were secondary biliary cirrhosis (SBC) (two cases) and alcoholic
      liver disease (one case). Clinical presentation included jaundice,
      gastrointestinal bleeding and ascites. One patient with SBC successfully
      underwent excision with Rouxen-Y hepaticojejunostomy, while the patient with
      cholangitis was managed with endoscopic retrograde cholangiopancreatography
      stenting. The last patient with alcoholic liver disease was managed
      conservatively for seven years and died of liver failure. Management of
      choledochal cysts depends on the severity of liver disease in cases of cirrhosis
      of unrelated cause, while those with SBC should be considered for surgical
      management. Endoscopic stenting may be considered as a temporary measure in high
      risk cases.

PMID- 22159944
TI  - Endovascular exclusion of aberrant splenic artery aneurysm with covered stent.
AB  - The splenic artery arising from the superior mesenteric artery is an uncommon
      anatomical variant. This aberrant origin may rarely be associated with an
      aneurysm. Previous cases have been managed with surgery and combined
      surgical/endovascular or endovascular techniques, with the latter involving
      occlusion of the aneurysm with coils. We report a case of aberrant splenic artery
      aneurysm that was excluded with a balloon-mounted covered stent, and discuss the
      technical issues encountered in using this approach. A follow-up computed
      tomography performed six months after the covered stent placement showed
      persistent exclusion with marked shrinkage of the aneurysm sac.

PMID- 22159945
TI  - Colonic perforation caused by direct trauma during computed tomographic
      colonography performed via end colostomy.
AB  - We report the case of a woman with a history of abdominoperineal resection for
      cancer, who had an inadvertent perforation during screening computed tomographic
      colonography performed via end colostomy. Revision of the stoma was promptly
      performed, which prevented a full laparotomy. We reviewed the literature on the
      subject and found that such perforations may be more common than previously
      thought. With appropriate precautions, such occurrences can be minimised in the
      future.

PMID- 22159946
TI  - Paraganglioma with acute hyperamylasaemia masquerading as acute pancreatitis.
AB  - Phaeochromocytomas are rare catecholamine-producing tumours. Although classically
      described to present with headache, diaphoresis and palpitations, they also
      present in unusual ways; hyperamylasaemia is one such rare presentation. We
      describe a man with an extra-adrenal phaeochromocytoma (paraganglioma) presenting
      with diaphoresis, abdominal pain and multi-organ failure. He had hyperamylasaemia
      of 1,087 (normal range [NR] 44-161) U/L, which mimicked acute severe
      pancreatitis. Serum lipase and radiographic imaging of the pancreas appeared
      normal, and the serial amylase levels normalised over six days upon stabilisation
      of his condition. 24-hour urinary metanephrines of 10,406 (NR 400-1,500) nmol/day
      suggested a catecholamine-secreting tumour, and metaiodobenzylguanine
      scintigraphy confirmed this. We postulate that amylase (of the salivary isotype)
      is released by hypoxic tissues when high catecholamine levels cause
      vasoconstriction and that fluctuating hypotension decreases organ perfusion. This
      case highlights the need for awareness of rare presentations of
      phaeochromocytomas and encourages physicians to rethink the diagnosis when
      investigations are inconsistent.

PMID- 22159947
TI  - Proliferating tricholemmal tumour: clinicopathological aspects of a case.
AB  - We report the case of a 49-year-old man who presented with an enlarging mass over
      his occipital scalp. The clinical impression was either a squamous cell carcinoma
      or an unusual adnexal tumour. A wide excision was performed with skin grafting.
      Gross examination revealed a large exophytic tumour mass measuring 10 cm.
      Histopathological examination showed a circumscribed, well-differentiated
      squamoproliferative lesion with a lobulated architecture. Clear cell features,
      pilar-type keratinisation, microcalcifications and the presence of mucinous
      degeneration were noted. A diagnosis of proliferating tricholemmal tumour was
      made. This entity incorporates a spectrum of lesions, ranging from the mostly
      benign proliferating tricholemmal cyst to tumours having more atypical cellular
      and invasive features, the latter features correlating with an increased capacity
      for aggressive behaviour. Management-wise, such tumours require complete excision
      with follow-up. As the tumours are often large in size at presentation,
      reconstruction is required.

PMID- 22159948
TI  - Primary cutaneous precursor B-cell lymphoblastic lymphoma with late
      dissemination.
AB  - A 20-year-old woman presented with multiple painless nodular swellings on the
      skin of the extremities and face, without any systemic symptoms. Biopsy with
      immunohistochemistry revealed a diagnosis of precursor B-cell lymphoblastic
      lymphoma. There was no extracutaneous site of involvement. The patient denied
      chemotherapy and was subsequently lost to follow-up. She presented with
      symptomatic disseminated disease 18 months later and rapidly succumbed to her
      illness.

PMID- 22159949
TI  - Unique origin of the cystic artery.
AB  - The cystic artery (CA) is known to exhibit variations in its origin and branching
      pattern. This is attributed to the developmental changes occurring in the
      primitive ventral splanchnic arteries. During routine dissection of a male
      cadaver, we observed that the CA originated from the middle hepatic artery (MHA)
      at a distance of about 1 cm from its origin, and the MHA originated from the
      right hepatic artery at a distance of 2.1 cm from its origin. The CA traversed
      for a distance of 1.5 cm, giving off a branch to the cystic duct. It then passed
      anterior to the cystic duct. The origin of the CA was located to the left of the
      common hepatic duct, outside the Calot's triangle. The topographical anatomy of
      the arterial system of the hepatobiliary region and their anomalous origin should
      be considered during hepatobiliary surgeries. This knowledge is also important
      for interventional radiologists in routine clinical practice.

PMID- 22159950
TI  - Thyrolingual trunk arising from the common carotid bifurcation.
AB  - Carotid arteries and their branches exhibit a wide range of variations. However,
      variations in the origin of the thyrolingual trunk from the common carotid artery
      are rare. We observed a case of thyrolingual trunk arising from the bifurcation
      point of the right common carotid artery during a routine dissection class for
      medical undergraduates. The thyrolingual trunk was running medially and downward
      before dividing into the upper lingual artery and the lower superior thyroid
      artery. No such variation was noted from the bifurcation point of the left common
      carotid artery.

PMID- 22159951
TI  - Polymorphisms of miRNAs genes are associated with the risk and prognosis of
      coronary artery disease.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small, single-stranded, non-protein-coding
      RNAs of about 22 nucleotides. miRNA molecules have been identified that plays key
      roles in a broad range of physiologic and pathologic processes. Polymorphisms in
      the corresponding sequence space are likely to make a significant contribution to
      phenotypic variation. METHODS AND RESULTS: To assess the variations of rs11614913
      T -> C in hsa-mir-196a2 and rs3746444 A -> G in hsa-mir-499 in the complex
      etiology of coronary artery disease (CAD), 956 CAD patients diagnosed by coronary
      arterial angiography and 620 controls were enrolled. Among the patients, 785
      (785/956) had complete follow-ups for 42 months. The variant genotypes CC/CT of
      hsa-mir-196a2 rs11614913 T -> C were not associated with a significantly
      increased risk of CAD (adjusted OR = 1.02, 95% CI = 0.76-1.38), compared with
      wide genotype TT, but CC and CC/CT genotypes were associated with 34 and 35%
      increased risks of serious prognosis of CAD (adjusted HR = 1.34, 95% CI = 1.02
      1.75 for CC; adjusted HR = 1.35, 95% CI = 1.03-1.75 for CC/CT). In the variant of
      hsa-mir-499 rs3746444A -> G, GG was associated with the 223% increased risk of
      CAD (adjusted OR = 3.23, 95% CI = 1.56-6.67). Cox regression analysis showed that
      age, smoking status, numbers of pathological changes in coronary arteries,
      rs11614913 T -> C, and diabetes mellitus were associated with serious prognosis
      of CAD. CONCLUSION: Our findings strongly implicate the functional miRNAs
      polymorphisms of hsa-mir-196a2 and hsa-mir-499 genes may modulate the occurrence
      or prognosis in Chinese CAD.

PMID- 22159953
TI  - Whatever happened to thiazides?

PMID- 22159952
TI  - Serum vitamin D concentration status and its correlation with early biomarkers of
      remodeling following acute myocardial infarction.
AB  - BACKGROUND: Low serum level of vitamin D was shown to be associated with
      cardiovascular diseases as well as the presence of diabetes, dyslipidemia, and
      hypertension. Vitamin D deficiency is a global problem, and is an Iranian problem
      as well. To the best of our knowledge, this was the first study on acute
      myocardial infarction that evaluates the correlation of vitamin D level with
      inpatients' outcomes, particularly on the early biomarkers of myocardial
      remodeling. METHODS: In a prospective study, patients with acute ST segment
      elevation myocardial infarction were included. The patients' 25 (OH) D levels
      were identified and the associations with clinical characteristics, including
      early remodeling biomarkers and in-hospital outcomes, were investigated. RESULTS:
      From the 139 included patients, 80.5% were male. The 25 (OH) deficiency was
      present in 72.7% of the patients. Hypertension and positive history of
      cardiovascular drug use were risk factors for the presence of low vitamin D
      levels (OR = 2.92; CI = 1.34-6.37, P < 0.05) and (OR = 2.36; CI = 1.05-5.29, P <
      0.05), respectively. Moreover, a significant positive relationship between the
      inpatients' survival and the concentration of vitamin D was present (P < 0.001).
      By performing a multivariate analysis, we found that there was a significant
      inverse relationship between the level of 25 (OH) D and the level of MMP-9 after
      72 h (P = 0.011). CONCLUSION: The results of our study revealed a significant
      inverse relationship between serum MMP-9 as a biomarker of early remodeling and
      the level of 25(OH) D in patients after an acute myocardial infarction. Moreover,
      low level of vitamin D was associated with patients' mortality in this study.

PMID- 22159954
TI  - Headgroup conformations of phospholipids from molecular dynamics simulation:
      sampling challenges and comparison to experiment.
AB  - The preferred conformations of the glycerol region of a phospholipid have been
      explored using replica exchange molecular dynamics (MD) simulations and compared
      with the results of standard MD approaches and with experiment. We found that due
      to isomerization rates in key torsions that are slow on the timescale of
      atomistic MD simulations, standard MD is not able to produce accurate equilibrium
      conformer distributions from reasonable trajectory lengths (e.g., on the 100 ns)
      timescale. Replica exchange MD, however, results in quite efficient sampling due
      to the rapid increase in isomerization rate with temperature. The equilibrium
      distributions obtained from replica exchange MD have been compared with the
      results of experimental nuclear magnetic resonance observations. This comparison
      suggests that the sampling approach demonstrated here is a valuable tool that can
      be used in evaluating force fields for molecular simulation of lipids.

PMID- 22159955
TI  - Aerobic fitness related to cardiovascular risk factors in young children.
AB  - Low aerobic fitness (maximum oxygen uptake (VO(2 PEAK))) is predictive for poor
      health in adults. In a cross-sectional study, we assessed if VO(2 PEAK) is
      related to a composite risk factor score for cardiovascular disease (CVD) in 243
      children (136 boys and 107 girls) aged 8 to 11 years. VO(2 PEAK) was assessed by
      indirect calorimetry during a maximal exercise test and scaled by body mass
      (milliliters per minute per kilogram). Total body fat mass (TBF) and abdominal
      fat mass (AFM) were measured by Dual-energy X-ray absorptiometry. Total body fat
      was expressed as a percentage of total body mass (BF%) and body fat distribution
      as AFM/TBF. Systolic and diastolic blood pressure (SDP and DBP) and resting heart
      rate (RHR) were measured. The mean artery pressure (MAP) and pulse pressure (PP)
      were calculated. Echocardiography, 2D-guided M-mode, was performed. Left atrial
      diameter (LA) was measured and left ventricular mass (LVM) and relative wall
      thickness (RWT) were calculated. Z scores (value for the individual - mean value
      for group)/SD were calculated by sex. The sum of z scores for DBP, SDP, PP, MAP,
      RHR, LVM, LA, RWT, BF%, AFM and AFM/TBF were calculated in boys and girls,
      separately, and used as composite risk factor score for CVD. Pearson correlation
      revealed significant associations between VO(2 PEAK) and composite risk factor
      score in both boys (r = -0.48 P < 0.05) and in girls (r = -0.42, P < 0.05). One
      way ANOVA analysis indicated significant differences in composite risk factor
      score between the different quartiles of VO(2 PEAK) (P < 0.001); thus, higher
      VO(2 PEAK) was associated with lower composite risk factor score for CVD. In
      conclusion, low VO(2 PEAK) is associated with an elevated composite risk factor
      score for CVD in both young boys and girls.

PMID- 22159956
TI  - A newborn with unilateral limb enlargement.
AB  - On routine neonatal examination, a newborn term male was noted to have unilateral
      enlargement of the right lower limb, loose thickened red skin over the palm and
      widening of all the fingers on the right hand. His body was pinker and warmer on
      the right side compared with the left and he had a right undescended testicle and
      hypoplastic scrotum. Radiological examination of the lower limbs demonstrated the
      enlargement of the soft tissue of the right lower limb compared to the left (Fig.
      1). Therefore, the diagnosis was unclear from this constellation of findings and
      an ophthalmic assessment was requested.

PMID- 22159957
TI  - Panton-Valentine leukocidin-associated Staphylococcus aureus necrotizing
      pneumonia in infants: a report of four cases and review of the literature.
AB  - Four children under 16 months of age presented within an 18-month period with
      severe, rapidly progressive Panton-Valentine leukocidin-associated ST93
      Staphylococcus aureus necrotizing pneumonia. Two of the cases that required
      extracorporeal membranous oxygenation and proved fatal had poor prognostic
      features of leukopenia, rash and pulmonary haemorrhage. All four cases had recent
      contact with S. aureus infection in a family member. Reported cases of S. aureus
      necrotizing pneumonia in infants are reviewed, and approach to management is
      discussed.

PMID- 22159958
TI  - A novel TFF2 splice variant (?EX2TFF2) correlates with longer overall survival
      time in cholangiocarcinoma.
AB  - Trefoil factor 2 (TFF2) is a member of trefoil factor family found to be
      overexpressed in many cancers including cholangiocarcinoma (CCA). The majority of
      studies have focused on wild-type TFF2 (wtTFF2) expression, but information
      regarding alternative splicing variants of TFF2 mRNA has not been reported. In
      this study, we aimed to identify and quantify a novel TFF2 splice variant in
      cholangiocarcinoma (CCA). Seventy-eight tumors and 15 normal adjacent tissues
      were quantified for the expression of the TFF2 splice variant relative to wild
      type (wt) TFF2 mRNA using quantitative reverse transcriptase polymerase chain
      reaction (QRT-PCR). The ratio of TFF2 splice variant against wtTFF2 was analyzed
      for associations with clinical parameters. We found a novel TFF2 splice variant,
      exon 2 skipping (?EX2TFF2), resulting in a stop codon (TAG) at exon 1. The
      ?EX2TFF2/wtTFF2 ratio in tumors was significantly higher than in normal tissue
      (P<0.01). Interestingly, high ?EX2TFF2/wtTFF2 ratio was significantly associated
      with good prognosis compared with low ratio (P=0.017). In contrast, the presence
      of wtTFF2 protein was associated with poor survival of CCA patients (P=0.034).
      This is the first report of a trefoil factor splice variant and its potential
      application as a prognostic biomarker in CCA.

PMID- 22159959
TI  - Gastrostomy tube placement without nasogastric tube: a retrospective evaluation
      in 85 patients.
AB  - PURPOSE: Our study evaluated techniques for percutaneous gastrostomy (G)-tube
      placement without the use of a nasogastric (NG) tube. Instead, direct puncture of
      a physiologic air bubble or effervescent-enhanced gastric bubble distention was
      performed in patients with upper digestive tract obstruction (UDTO) or
      psychological objections to NG tubes. MATERIALS AND METHODS: A total of 886
      patients underwent G-tube placement in our department during a period of 7 years.
      We present our series of 85 (9.6%) consecutive patients who underwent
      percutaneous G-tube placement without use of an NG tube. RESULTS: Of these 85
      patients, fluoroscopic guided access was attempted by direct puncture of a
      physiologically present gastric air bubble in 24 (28%) cases. Puncture of an
      effervescent-induced large gastric air bubble was performed in 61 (72%) patients.
      Altogether, 82 (97%) of 85 G tubes were successfully placed in this fashion. The
      three failures comprised refusal of effervescent, vomiting of effervescent, and
      one initial tube misplacement when a deviation from our standard technique
      occurred. CONCLUSION: The described techniques compare favorably with published
      large series on G-tube placement with an NG tube in place. The techniques are
      especially suited for patients with UDTO due to head, neck, or esophageal
      malignancies, but they should be considered as an alternative in all patients.
      Direct puncture of effervescent-enhanced gastric bubble distention is a safe,
      patient-friendly and effective technique.

PMID- 22159960
TI  - Thermally modulated multilayered graphene oxide for hydrogen storage.
AB  - We have obtained high pressure H(2) isotherms with respect to the interlayer
      distance of multilayered graphene oxide (GO) modulated by thermal annealing. The
      maximum storage capacity is 4.8 (0.5) wt% at 77 K (298 K) and at 9.0 MPa
      pressure. We found the optimum GO interlayer distance for maximum H(2) uptake at
      6.5 A, similar to the predicted distances from first-principles calculations for
      graphite materials. Our results reveal that multilayered GO can be a practical
      material of choice to allow the use of graphene as a hydrogen storage material,
      provided that only small amounts of O and OH functional groups exist as spacers
      on GO sheets.

PMID- 22159961
TI  - Intervening in clinical research to prevent the onset of psychoses: conflicts and
      obligations.
AB  - A prevailing issue in clinical research is the duty clinicians have to treat or
      prevent the progression of disease during a study that they are conducting. While
      all clinical researchers have a duty of care for the patients who participate in
      clinical research, intervening at the onset or progression of disease may skew
      results and have a negative impact on the scientific validity of a study. Extreme
      examples of failures to intervene can be found in the Tuskegee syphilis study and
      in an attempt to determine if cervical smears were an accurate predictor of
      cancer, which was uncovered by the Cartwright Inquiry. However, the issue arises
      in all research where delay in intervention can cause harm. A current study in
      Singapore is investigating the significance of an 'ultra-high risk' state that
      may constitute the prodromal phase of psychosis. This project called 'The
      Longitudinal Youth at Risk Study' is potentially contentious because it is
      recruiting young people who are identified as being 'at risk' of developing
      psychosis. In this paper, the decision to offer treatment to all participants as
      well as a fast track for those who are assessed to have developed serious mental
      illness into treatment is discussed. It is argued that this approach is ethically
      justified because of the duty of care that is owed to research participants, and
      suggests that the principle of equipoise may be used to guide intervention
      decisions in other clinical research protocols.

PMID- 22159963
TI  - Expression of the major mugwort pollen allergen Art v 1 in tobacco plants and
      cell cultures: problems and perspectives for allergen production in plants.
AB  - An economic and cheap production of large amounts of recombinant allergenic
      proteins might become a prerequisite for the common use of microarray-based
      diagnostic allergy assays which allow a component-specific diagnosis. A molecular
      pharming strategy was applied to express the major allergen of Artemisia vulgaris
      pollen, Art v 1, in tobacco plants and tobacco cell cultures. The original Art v
      1 with its endogenous signal peptide which directs Art v 1 to the secretory
      pathway, was expressed in transiently transformed tobacco leaves but was lost in
      stable transformed tobacco plants during the alternation of generations. Using a
      light-regulated promoter and "hiding" the recombinant Art v 1 in the ER succeeded
      in expression of Art v 1 over three generations of tobacco plants and in cell
      cultures generated from stable transformed plants. However, the amounts of the
      recombinant allergen were sufficient for analysis but not high enough to allow an
      economic production. Although molecular pharming has been shown to work well for
      the production of non-plant therapeutic proteins, it might be less efficient for
      closely related plant proteins.

PMID- 22159962
TI  - Current status and perspectives of plant-based candidate vaccines against the
      human immunodeficiency virus (HIV).
AB  - Genetically engineered plants are economical platforms for the large-scale
      production of recombinant proteins and have been used over the last 21 years as
      models for oral vaccines against a wide variety of human infectious and
      autoimmune diseases with promising results. The main inherent advantages of this
      approach consist in the absence of purification needs and easy production and
      administration. One relevant infectious agent is the human immunodeficiency virus
      (HIV), since AIDS evolved as an alarming public health problem implicating very
      high costs for government agencies in most African and developing countries. The
      design of an effective and inexpensive vaccine able to limit viral spread and
      neutralizing the viral entry is urgently needed. Due to the limited efficacy of
      the vaccines assessed in clinical trials, new HIV vaccines able to generate broad
      immune profiles are a priority in the field. This review discusses the current
      advances on the topic of using plants as alternative expression systems to
      produce functional vaccine components against HIV, including antigens from Env,
      Gag and early proteins such as Tat and Nef. Ongoing projects of our group based
      on the expression of chimeric proteins comprising C4 and V3 domains from gp120,
      as an approach to elicit broadly neutralizing antibodies are mentioned. The
      perspectives of the revised approaches, such as the great need of assessing the
      oral immunogenicity and a detailed immunological characterization of the elicited
      immune responses, are also discussed.

PMID- 22159964
TI  - Modulation of ethanol stress tolerance by aldehyde dehydrogenase in the
      mycorrhizal fungus Tricholoma vaccinum.
AB  - We report the first mycorrhizal fungal aldehyde dehydrogenase gene, ald1, which
      was isolated from the basidiomycete Tricholoma vaccinum. The gene, encoding a
      protein Ald1 of 502 amino acids, is up-regulated in ectomycorrhiza. Phylogenetic
      analyses using 53 specific fungal aldehyde dehydrogenases from all major phyla in
      the kingdom of fungi including Ald1 and two partial sequences of T. vaccinum were
      performed to get an insight in the evolution of the aldehyde dehydrogenase
      family. By using competitive and real-time RT-PCR, ald1 is up-regulated in
      response to alcohol and aldehyde-related stress. Furthermore, heterologous
      expression of ald1 in Escherichia coli and subsequent in vitro enzyme activity
      assay demonstrated the oxidation of propionaldehyde and butyraldehyde with
      different kinetics using either NAD(+) or NADP(+) as cofactors. In addition,
      overexpression of ald1 in T. vaccinum after Agrobacterium tumefaciens-mediated
      transformation increased ethanol stress tolerance. These results demonstrate the
      ability of Ald1 to circumvent ethanol stress, a critical function in mycorrhizal
      habitats.

PMID- 22159965
TI  - In vitro and in vivo studies on the use of Histoacryl((r)) as a soft tissue glue.
AB  - The skin adhesive Histoacryl((r)) consists of n-butyl-2-cyanoacrylate which
      polymerises in contact with moisture. It is not fully biodegradable, produces
      heat during polymerisation and releases products which are toxic and inhibit cell
      growth. Clinical application is exclusively approved to glue skin. However, there
      are also clinical studies and case reports in the scientific literature, which
      discuss the application of Histoacryl((r)) as a soft tissue adhesive. In parallel
      to an analysis of the literature which discusses the usage of Histoacryl((r)) in
      head and neck surgery, we performed in vitro and in vivo investigations with this
      adhesive. In vitro, the vitality of cultured cell lines which where treated with
      extracts of Histoacryl((r)) was determined with a viability assay. In addition,
      Histoacryl((r)) was examined by fixing defined mucous membrane of the nasal
      septum in an animal study in rabbits. The analysis of the literature shows both
      positive and negative results for the application of Histoacryl((r)) as a soft
      tissue adhesive depending on the manner and place of the application as well as
      the applied amount of glue. Our own results confirm a negative influence of
      Histoacryl((r)) on the viability of cultured cells and soft tissue. The
      histological examination showed that a better biocompatibility is achieved if the
      glue is used in small amounts. Both the literature study as well as the in vitro
      and in vivo examinations showed that the usage of Histoacryl((r)) as a soft
      tissue glue may be arguable. Critical factors are the moisture at the application
      area and the applied amount of glue.

PMID- 22159966
TI  - Topical Mitomycin C in functional endoscopic sinus surgery.
AB  - In recent literature, there has been an interest in the use of Mitomycin C to
      reduce post-operative complications following endoscopic sinus surgery. We report
      our results on a prospective, randomized controlled trial involving 50 patients
      with chronic bilateral rhino sinusitis. We eliminated various confounding factors
      by studying a single group of patients, with symmetrical disease, without pre
      existing gross anatomical abnormalities. Patients requiring revision sinus
      surgery were excluded. On completion of the surgery, a cotton pledget soaked in
      Mitomycin C was placed in one nostril (test) and saline-soaked pledget (control)
      was placed in the other side of the nose, both in the middle meatus. The side of
      the nasal cavity receiving the topical Mitomycin C was randomized. The patients
      were assessed periodically (first week, first month, third month and sixth month)
      for synechiae formation and presence or absence of their symptoms. At the first
      week follow up, there was a statistically significant difference in the incidence
      of synechiae between the saline and Mitomycin C side. Furthermore, there was a
      statistically significant improvement with regards to patient symptoms (nasal
      block and discharge) in the Mitomycin C side when compared to the saline side. At
      the third and sixth month, there was no difference between the two groups. The
      incidence of adverse tissue reaction (granulation, discharge, polypoidal mucosa
      and crusting) was less in the Mitomycin C side when compared to the saline side
      at the first month follow up. Topically applied Mitomycin C reduces the incidence
      of synechiae in the immediate post-operative period in patients undergoing
      endoscopic sinus surgery. There is also an improvement in nasal obstruction and
      discharge with a reduction in the incidence of adverse tissue reaction in the
      early post-operative period.

PMID- 22159967
TI  - Harmonic scalpel versus bipolar tonsillectomy: a double-blind clinical trial.
AB  - This is a double bind clinical trial which evaluated harmonic scalpel versus
      bipolar diathermy tonsillectomy The study was conducted at Diyarbakir government
      hospital, Diyarbakir, Turkey. The study population comprised 144 patients, aged 4
      18 years (mean 9 years +/- 4.12 SD). All patients underwent tonsillectomy with or
      without adenoidectomy. The indications for tonsillectomy were obstructive sleep
      apnea (84 patients [58.3%]) and chronic tonsillitis (60 patients [41.7%]). All
      144 patients were randomly divided into two groups: bipolar dissection (81
      patients [56.2%] with mean age 8.98 years +/- 4.22) and harmonic scalpel (63
      patients [43.8%] with mean age 9 years +/- 4.02). BD group showed statistically
      significantly less intraoperative bleeding (< 0.05). There was no statistically
      significant difference on postoperative day 1 but a statistically significant
      difference was determined on postoperative days 4, 7 and 14. There was no
      statistically significant difference between the two techniques with regard to
      immediate and delayed bleeding. The mean operative time was the same in both the
      groups. Bipolar dissection group showed statistically significant less
      intraoperative bleeding than harmonic scalpel group. An analysis of postoperative
      pain scores showed that the harmonic scalpel group pain scores are lower than the
      bipolar dissection group on all recorded days, and no statistically significant
      complications was seen in both groups. The results of this study indicate that
      the HS technique is associated with lower pain scores with the same complication
      rates as the BD technique.

PMID- 22159969
TI  - Internet sites offering adolescents help with headache, abdominal pain, and
      dysmenorrhoea: a description of content, quality, and peer interactions.
AB  - OBJECTIVES: To analyze content and quality of headache, abdominal pain, and
      dysmenorrhoea websites, and to thematically analyze online pain forums. METHODS:
      Websites offering support, advice, or information regarding pain were explored.
      Websites were analyzed quantitatively using the Health-Related Website Evaluation
      Form and the DISCERN scale. Websites containing forum functions were thematically
      analysed assessing how the Internet is used for support and advice. RESULTS: 63
      websites were included. Few websites scored in the upper quartiles of scores on
      the measures. 7 websites contained supportive posts, pertaining only to
      dysmenorrhoea. The ways users cope and the coping judgements of other forum users
      are presented thematically. 3 themes emerged: (1) passively engaged postings, (2)
      actively engaged postings, and (3) reactively engaged postings. CONCLUSIONS:
      Internet pain resources are of low quality and questionable value in providing
      help to adolescents. Future research should explore how to improve quality.

PMID- 22159968
TI  - Subconscious olfactory influences of stimulant and relaxant odors on immune
      function.
AB  - Brain and immune system are linked by bidirectional pathways so that changes of
      the central nervous system may influence various immune functions. The olfactory
      system may be involved in this interaction. In most odor studies subjects are
      aware of an odor exposure, using frequently high odor concentrations or long-term
      exposures without controls. In this pilot study, the potential immune effects of
      short-term odor exposure were examined in 32 blinded subjects (16 male, 16
      female). Subjects were exposed without their knowledge either to a stimulant
      essential oil (grapefruit, fennel, pepper), a no-odor control or a relaxant
      essential oil (lavender, patchouli, rose) during a set of psychological
      questionnaires for 30 min at three separate visits. Activity of neutrophil
      granulocytes (CXCL8 release, CD16) and peripheral blood concentrations of mainly
      neutrophil-related immunological markers were measured. We tested the triple of
      stimulant odor, control and relaxant odor for every subject in a model which
      assumed opposite effects of the stimulant and the relaxant odor. This hypothesis
      was falsified by our experimental data, as no significant effect was observed for
      the parameters tested. The human immune functions tested in our study are not
      modulated by short-term odor exposure in blinded subjects. Further studies should
      directly dissect possible differences between long-term and short-term exposures
      of non-blinded subjects versus blinded subjects.

PMID- 22159970
TI  - Agreement with night-waking strategies among community mothers of preschool-aged
      children.
AB  - OBJECTIVE: To explore the night-waking schemas of mothers of preschool-aged
      children, using a new measure of agreement with night-waking strategies (Night
      waking Vignettes Scale; NVS). METHOD: A community sample of 203 mothers (M age =
      32 years, SD = 5.1) of 2- to 5-year-olds (M age = 3.4 years, SD = 1.0) provided
      demographic information and completed the NVS and measures of night-waking and
      general parenting behavior. RESULTS: Few mothers endorsed strong agreement or
      disagreement with limit-setting, active comforting, or rewards; mothers generally
      disagreed with punishment. Significant associations between agreement with night
      waking strategies, child sex, and maternal educational attainment were observed;
      only agreement with punishment was correlated with general parenting. Agreement
      with night-waking strategies differed across the night-waking behaviors depicted
      in the NVS vignettes. Agreement with limit-setting and agreement with active
      comforting were correlated with night-waking. CONCLUSIONS: Mothers may be
      ambivalent about common night-waking strategies. Night-waking schemas appear to
      be complex.

PMID- 22159971
TI  - Commentary: health and behavior codes in a pediatric headache program:
      reimbursement data and recommendations for practice.

PMID- 22159972
TI  - Family courts, risk assessment, and the moral compass.

PMID- 22159973
TI  - Physicians as gatekeepers in the use of medical marijuana.

PMID- 22159974
TI  - Restraint and seclusion in psychiatric treatment settings: regulation, case law,
      and risk management.
AB  - Changing federal regulations, civil rights and malpractice cases, and new
      treatment methods have influenced the use of restraint and seclusion (R&S) in
      inpatient psychiatric treatment settings, such that restraint and seclusion today
      are among the most highly regulated practices in psychiatry. Despite increased
      pressure from regulatory bodies and litigation, the use of R&S remains
      controversial and risky. These procedures can compromise safety if performed
      incorrectly or monitored inadequately, but intervention by restraint or seclusion
      may be necessary to maintain safety on the treatment unit, especially during
      emergencies. Case law and medical research have demonstrated the importance of a
      patient-focused, treatment-oriented approach toward risk management. Analysis of
      specific clinical scenarios can help to develop risk mitigation strategies that
      are therapeutically conceptualized rather than driven by regulation. Insights
      drawn from clinical cases that have resulted in litigation can offer an
      opportunity to develop an approach oriented to patient care from a clinical or
      risk management perspective. In this article, we seek to provide a foundation for
      evaluation of current protocols, an analysis of adverse R&S events, and
      strategies to minimize risk.

PMID- 22159975
TI  - Commentary: On regulation, wishfulness, and denial.
AB  - Restraint and seclusion are unsavory topics within a discipline that cherishes
      verbal interventions. As such, the principles of use are haphazardly taught by in
      house clinicians or private agencies. Policy standards were published in the
      1980s, but they have not been officially updated, despite the fact that an
      American Psychiatric Association (APA) committee met in 2003 to overhaul the
      standards of care. In training programs, violence is given little syllabus space,
      compared with the treatment of mood and thought disorders. Aggression remains a
      stepchild symptom, even though it is frequently encountered in clinical practice.

PMID- 22159976
TI  - Commentary: Interventions based on learning principles can supplant seclusion and
      restraint.
AB  - Regulatory and administrative imperatives, when paired with staff training in
      humanistic, verbally mediated interventions can reduce the frequency of seclusion
      and restraint but can be associated with increases in the frequency and severity
      of staff injury, with concomitant tension and apprehension in the treatment
      setting. Even when educational programs for staff are made available for patient
      centered, therapeutic, and persuasion-based modes of de-escalation, aggression,
      destructiveness and self-injury may continue to occur or even increase.
      Administrative contingencies can lead to less reporting of such incidents by
      staff with consequential, adverse effects on their morale and the unit milieu.
      Given the neurocognitive deficits, learning disabilities and lengthy histories of
      inadvertent reinforcement of provocative and aggressive behavior among persons
      with developmental and serious psychiatric disorders, basic principles of
      learning are needed to teach alternatives for belligerent behavior. Examples of
      behavior therapies that have been documented as effective in reducing aggression
      and self-injury include differential reinforcement of other behavior, social
      skills training, teaching interaction, social learning modalities, and time out
      from reinforcement. These evidence-based behavioral interventions must be
      superimposed on optimal, diagnostically driven, and monitored pharmacotherapy.
      When evidence-based, person-centered, and recovery-oriented biobehavioral
      interventions are made available to inpatient units, favorable clinical outcomes
      with reductions in the use of seclusion and restraint are likely.

PMID- 22159977
TI  - Diagnosing and litigating hebephilia in sexually violent predator civil
      commitment proceedings.
AB  - In recent years, state and federal legislative initiatives have heavily
      emphasized punitive laws to combat sexual crime. These statutes include
      indefinite civil commitment, which is the ultimate infringement on sexual
      offenders' civil liberties. Many of these committed offenders have repeatedly
      offended against prepubescent children (pedophiles), and many have committed
      nonconsensual sexual offenses against adults (rapists). A substantial number of
      sex offenders have offended against postpubescent adolescents and teenagers
      outside the age range of pedophilia (commonly referred to by some clinicians and
      researchers as hebephilia). The use of the term hebephilia has recently received
      heightened scrutiny in sexually violent predator civil commitment proceedings.
      Specifically, experts debate whether hebephilia is recognized within the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision (DSM-IV-TR) and whether it is a generally accepted diagnosis within the
      field of sexual offender assessment. Scholars and practitioners question how
      hebephilia pertains to sexual deviance and one's risk of reoffending and whether
      it ultimately meets the legal mental abnormality threshold of civil commitment
      through DSM diagnostic criteria. This article addresses these questions and
      provides recent federal case law that attends to hebephilia in sexually violent
      predator proceedings.

PMID- 22159978
TI  - Commentary: Hebephilia--a would-be paraphilia caught in the twilight zone between
      prepubescence and adulthood.
AB  - This commentary addresses the controversy surrounding the proposed Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Revision (DSM-5) diagnosis of
      pedohebephilia. We examine adult male sexual attraction to young pubescent
      females and whether such attraction is deviant and constitutes a mental disorder,
      and, independent of that question, whether there is any defensible basis for
      asserting that hebephilia is a legitimate paraphilia. We conclude our analysis by
      looking at three profiles: adults with sexualized interest in pre- and
      postpubescent children, adults with sexualized interest in adult and pubescent
      adolescent women, and adults with exclusive sexualized interest in young
      pubescent women. We suggest that in the third instance of exclusivity, the
      Criterion B requirement of impairment may become critical to legitimizing a
      diagnosis of hebephilia.

PMID- 22159979
TI  - Diffusion tensor imaging in mild traumatic brain injury litigation.
AB  - A growing body of literature addresses the application of diffusion tensor
      imaging (DTI) to traumatic brain injury (TBI). Most TBIs are of mild severity,
      and their diagnosis and prognosis are often challenging. These challenges may be
      exacerbated in medicolegal contexts, where plaintiffs seek to present objective
      evidence that supports a clinical diagnosis of mild (m)TBI. Because DTI permits
      quantification of white matter integrity and because TBI frequently involves
      white matter injury, DTI represents a conceptually appealing method of
      demonstrating white matter pathology attributable to mTBI. However, alterations
      in white matter integrity are not specific to TBI, and their presence does not
      necessarily confirm a diagnosis of mTBI. Guided by rules of evidence shaped by
      Daubert v. Merrell Dow Pharmaceuticals, Inc., we reviewed and analyzed the
      literature describing DTI findings in mTBI and related neuropsychiatric
      disorders. Based on this review, we suggest that expert testimony regarding DTI
      findings will seldom be appropriate in legal proceedings focused on mTBI.

PMID- 22159980
TI  - The effect of length of hospitalization on re-arrest among insanity plea
      acquittees.
AB  - State psychiatric hospitals are increasingly populated by forensic patients. In
      New York State, the growth in the forensic population is largely attributable to
      increased lengths of stay of patients deemed not guilty by reason of insanity
      (NGRI). This research was conducted to determine whether longer periods of
      hospitalization are associated with better outcomes in the community, as measured
      by re-arrest for any offense and re-arrest for violence. The sample included 386
      NGRI patients released into the community in New York State. A Cox regression
      proportional hazards model was used to assess the unique effects of length of
      hospitalization on re-arrest. The results showed that the length of treatment had
      little effect on either measure of re-arrest. Re-arrest was largely explained by
      demographics and prior criminal histories.

PMID- 22159981
TI  - "I did what?" Zolpidem and the courts.
AB  - Zolpidem is a widely prescribed nonbenzodiazepine hypnotic medication available
      in the United States since 1992. Attention has been drawn recently to its
      potential to cause sleep-related, complex behaviors such as sleepwalking and
      sleep driving. These automatic behaviors have led to a deluge of legal claims. To
      the authors' knowledge, this is the first review in the forensic literature of
      the legal ramifications of zolpidem. In this article, the medical literature will
      be reviewed to explore the current understanding of zolpidem's specific
      psychopharmacology. Case law will be explored to determine how the courts have
      handled the claims surrounding sleep-related, complex behaviors alleged to be
      caused by zolpidem. Finally, a summary of recommendations will be provided for
      forensic psychiatrists who are asked to be experts in these cases.

PMID- 22159982
TI  - Assessing the risk of violent behavior before issuing a license to carry a
      handgun.
AB  - Handguns are intended to be used for protection, but they can also be used as
      weapons of assault that may endanger others or inflict self-harm and facilitate
      suicide. Research has revealed a direct correlation between firearm availability
      and suicide risk. Gun control is intended to reduce violence through legislation
      that restricts ownership and use of firearms. How can we ensure that firearms
      will not reach the hands of individuals who may pose a danger to themselves or to
      others, without infringing on the rights of other citizens to carry guns for
      protection, which is in the public interest? The potential to commit a crime will
      materialize, depending on dynamic interactions among personality factors,
      environmental factors, and the individual's history of offending. We present
      illustrative cases involving various aspects of gun control and a description of
      instruments for the assessment of dangerousness that can facilitate the licensing
      process for carrying and using firearms.

PMID- 22159983
TI  - Meeting the needs of those persons with serious mental illness who are most
      likely to become criminalized.
AB  - Persons with serious mental illness are a heterogeneous group. A large majority
      recognize that they are mentally ill, and they are treatment adherent, often able
      to work, and do not have major problems with substance abuse and violence.
      However, a substantial minority exists who receive little attention in the
      literature. They may not believe that they are mentally ill (the possible result
      of anosognosia), are nonadherent to psychiatric treatment, may have acute
      psychotic symptoms and serious substance abuse problems, may become violent when
      stressed, and may show less potential for recovery. This minority is at most risk
      for criminalization. High degrees of structure may help reduce this risk. They
      need a range of outpatient and inpatient treatment, including assertive community
      treatment, intensive case management, assisted outpatient treatment, structured
      housing, co-occurring substance abuse treatment, pre- and postbooking diversion,
      and available hospital beds. The mental health system can reduce criminalization
      by taking greater responsibility for these challenging persons.

PMID- 22159984
TI  - Paraphilia NOS, nonconsent: not ready for the courtroom.
AB  - Sexually violent predators (SVP) constitute a serious potential risk to public
      safety, especially when they are released after too short a prison sentence.
      Twenty states and the federal government have developed a seemingly convenient
      way to reduce this risk. They have passed statutes that allow for the involuntary
      (often lifetime) psychiatric commitment of mentally disordered sexual offenders
      after prison time is up. In three separate cases, the Supreme Court has accepted
      the constitutionality of this procedure, but only if the offender's dangerousness
      is caused by a mental disorder and is not a manifestation of simple criminality.
      The idea that paraphilic rape should be an official category in the psychiatric
      diagnostic manual has been explicitly rejected by Diagnostic and Statistical
      Manual of Mental Disorders (DSM)-III, DSM-III-R, DSM-IV, and, recently, DSM-5.
      Despite this, paraphilia NOS, nonconsent, is still frequently used by mental
      health evaluators in SVP cases to provide a mental disorder diagnosis that
      legitimizes psychiatric commitment and makes it appear constitutional. This
      commentary will show how the diagnosis paraphilia NOS, nonconsent, is based on a
      fundamental misreading of the original intent of the DSM-IV Paraphilia Workgroup
      and represents a misuse of psychiatry, all in the admittedly good cause of
      protecting public safety.

PMID- 22159985
TI  - Batterers: a review of violence and risk assessment tools.
AB  - Batterers are often identified in the criminal justice system after they have
      inflicted significant abuse on their victims. The increasing public health
      initiatives surrounding intimate partner violence focus on identification of
      victims and their protection. Little emphasis is placed, however, on the
      batterers themselves. Forensic specialists become involved in risk assessment for
      violence only after a perpetrator has inflicted significant damage on his victim
      and entered the criminal justice system. This article serves to bring awareness
      of the many factors, including neurobiology and neuropsychology, that contribute
      to the development of a batterer. Two instruments useful in identifying violence
      risk will be highlighted, along with a proposal for future research that could
      broaden risk assessment applications to other noncriminal settings, allowing for
      early detection and prevention of violent acts.

PMID- 22159986
TI  - Survey of forensic mental health experts on pro se competence after Indiana v.
      Edwards.
AB  - In Indiana v. Edwards (2008) the U.S. Supreme Court held that a higher standard
      may be required for pro se competence (PSC) than for competence to stand trial
      (CST), but provided little guidance for the trial court judge. This survey of
      forensic mental health experts studied potential PSC criteria. Sixty-eight
      (22.7%) forensic evaluators replied. Three McGarry criteria were reported as
      requiring a much higher standard for PSC: to appraise the available legal
      defenses (45.6%), to plan a legal strategy (51.5%), and to question and challenge
      witnesses (44.1%). Sixty percent agreed that standby counsel should be mandatory.
      Respondents opined that average abilities were sufficient for intelligence
      (77.9%), literacy (69.1%), and verbal ability (70.6%) were sufficient. PSC
      examiners may wish to assess appraisal of available legal defenses, planning a
      legal strategy, and questioning and challenging witnesses for a higher standard
      than CST. Evaluators should also assess the defendant's willingness to accept
      standby counsel (SBC) and the defendant's motivation for attempting a pro se
      defense.

PMID- 22159987
TI  - Cloudy confidentiality: clinical and legal implications of cloud computing in
      health care.
AB  - The Internet has grown into a world of its own, and its ethereal space now offers
      capabilities that could aid physicians in their duties in numerous ways. In
      recent years software functions have moved from the individual's local hardware
      to a central server that operates from a remote location. This centralization is
      called cloud computing. Privacy laws that speak to the protection of patient
      confidentiality are complex and often difficult to understand in the context of
      an ever-growing cloud-based technology. This article is a review of the legal
      background of protected health records, as well as cloud technology and physician
      applications. An attempt is made to integrate both concepts and examine Health
      Insurance Portability and Accountability Act (HIPAA) compliance for each of the
      examples discussed. The legal regulations that may inform care and standards of
      practice are reviewed, and the difficulties that arise in assessment and
      monitoring of the current situation are analyzed. For forensic psychiatrists who
      may be asked to provide expert opinions regarding malpractice situations
      pertaining to confidentiality standards, it is important to become acquainted
      with the new digital language from which these questions may arise.

PMID- 22159988
TI  - A reflection on violence.

PMID- 22159989
TI  - Incidence of inadvertent intra-articular lumbar facet joint injection during
      fluoroscopically guided interlaminar epidural steroid injection.
AB  - OBJECTIVE: To determine the incidence of inadvertent lumbar facet joint injection
      during an interlaminar epidural steroid injection (ESI). MATERIALS AND METHODS: A
      total of 686 interlaminar lumbar ESIs were performed from January 1, 2009 to
      December 31, 2009. Archived images from these cases were retrospectively reviewed
      on the PACS. Positive cases of inadvertent lumbar facet joint injection were
      identified by the characteristic sigmoid-shaped contrast pattern projecting over
      the posterior elements on the lateral view and/or ovoid contrast projecting over
      the facet joints on the anteroposterior (AP) view. RESULTS: Eight positive events
      were identified (1.2%). There was no statistically significant gender or lumbar
      level predilection. In 3/8 of the positive cases (37.5%), the inadvertent facet
      joint injection was recognized by the operator. The needle was repositioned as a
      result, and contrast within the posterior epidural space was documented by the
      end of the procedure. In 5/8 of the positive cases (62.5%), the patients reported
      an immediate decrease in the presenting pain. CONCLUSIONS: The incidence of
      inadvertent lumbar facet joint injection during an interlaminar epidural steroid
      injection is low. Recognizing the imaging features of this event permits the
      operator to redirect the needle tip into the epidural space and/or identify the
      facet joint(s) as a source of the patient's presenting pain.

PMID- 22159990
TI  - Dietary relationships among coexisting anuran amphibians: a worldwide
      quantitative review.
AB  - Anuran amphibians have traditionally been considered suitable model organisms for
      community ecology studies. In this paper, we review and quantitatively re-analyze
      the original studies published on dietary relationships among anuran communities
      worldwide. We re-analyzed 33 independent communities from all continents,
      including data on prey numbers and/or prey volumes. All datasets underwent null
      model re-analysis using two randomization algorithms. In addition, logistic
      regression models were used to identify specific assemblage patterns. We
      discovered three main patterns: (1) one particular algorithm (RA2, which replaces
      every cell in the matrix with one randomly chosen, but retains the zero structure
      of the matrix) performed much better at uncovering community structure; (2)
      nonrandom structure was more likely to occur in tropical than in nontropical
      regions; (3) prey volume was a better descriptor of dietary relationships than
      prey number when attempting to detect nonrandom structure. We showed that:
      pattern (1) depended on both the overall generalist nature of the anurans in
      general and on the mathematical properties of RA2; pattern (2) was consistent
      with theoretical attributes of tropicality; and pattern (3) was due to the
      intrinsic ecological properties of generalist organisms, which forage more or
      less opportunistically on prey of very different sizes; hence, when prey number
      is used as a diet descriptor, there is a risk of approximating different prey
      taxa that make different relative volume contributions to the overall diet as
      being of similar relevance .

PMID- 22159991
TI  - Associational resistance and associational susceptibility: specialist herbivores
      show contrasting responses to tree stand diversification.
AB  - Heterospecific neighbors may reduce damage to a focal plant by lowering
      specialist herbivore loads (associational resistance hypothesis), or enhance
      damage by increasing generalist herbivore loads (associational susceptibility
      hypothesis). We tested the associational effects of tree diversity on herbivory
      patterns of the tropical focal tree Tabebuia rosea in an experimental plantation
      setup, which contained tree monocultures and mixed stands. We found higher
      herbivore damage to T. rosea at higher tree diversity, indicating that T. rosea
      did not benefit from associational resistance but rather experienced
      associational susceptibility. The specific consideration of the two dominant
      insect herbivore species of T. rosea, the specialist chrysomelid Walterianella
      inscripta and the specialist pyralid Eulepte gastralis, facilitated understanding
      of the detected damage patterns. Tree diversity exerted opposite effects on tree
      infestation by the two herbivores. These findings point to resource concentration
      effects for the chrysomelid beetle (favored by tree monoculture) and to resource
      dilution effects for the pyralid caterpillar (favored by tree mixture) as
      underlying mechanisms of herbivore distribution. A strong contribution of the
      pyralid to overall damage patterns in diversified stands suggests that
      associational susceptibility may not necessarily be related to higher abundances
      of generalist herbivores but may also result from specialized herbivores affected
      by resource dilution effects. Thus, the identity and biology of herbivore species
      has to be taken into account when attempting to predict damage patterns in forest
      ecosystems.

PMID- 22159992
TI  - Relationships between the extent of apnea-induced bradycardia and the vascular
      response in the arm and leg during dynamic two-legged knee extension exercise.
AB  - Our aim was to test the hypothesis that apnea-induced hemodynamic responses
      during dynamic exercise in humans differ between those who show strong
      bradycardia and those who show only mild bradycardia. After apnea-induced changes
      in heart rate (HR) were evaluated during dynamic exercise, 23 healthy subjects
      were selected and divided into a large response group (L group; n = 11) and a
      small response group (S group; n = 12). While subjects performed a two-legged
      dynamic knee extension exercise at a work load that increased HR by 30 beats/min,
      apnea-induced changes in HR, cardiac output (CO), mean arterial pressure (MAP),
      arterial O(2) saturation (Sa(O(2))), forearm blood flow (FBF), and leg blood flow
      (LBF) were measured. During apnea, HR in the L group (54 +/- 2 beats/min) was
      lower than in the S group (92 +/- 3 beats/min, P < 0.05). CO, Sa(O(2)), FBF, LBF,
      forearm vascular conductance (FVC), leg vascular conductance (LVC), and total
      vascular conductance (TVC) were all reduced, and MAP was increased in both
      groups, although the changes in CO, TVC, LBF, LVC, and MAP were larger in the L
      group than in the S group (P < 0.05). Moreover, there were significant positive
      linear relationships between the reduction in HR and the reductions in TVC, LVC,
      and FVC. We conclude that individuals who show greater apnea-induced bradycardia
      during exercise also show greater vasoconstriction in both active and inactive
      muscle regions.

PMID- 22159993
TI  - Quantitative comparison of cardiac ventricular myocyte electrophysiology and
      response to drugs in human and nonhuman species.
AB  - Explanations for arrhythmia mechanisms at the cellular level are usually based on
      experiments in nonhuman myocytes. However, subtle electrophysiological
      differences between species may lead to different rhythmic or arrhythmic cellular
      behaviors and drug response given the nonlinear and highly interactive cellular
      system. Using detailed and quantitatively accurate mathematical models for human,
      dog, and guinea pig ventricular action potentials (APs), we simulated and
      compared cell electrophysiology mechanisms and response to drugs. Under basal
      conditions (absence of beta-adrenergic stimulation), Na(+)/K(+)-ATPase changes
      secondary to Na(+) accumulation determined AP rate dependence for human and dog
      but not for guinea pig where slow delayed rectifier current (I(Ks)) was the major
      rate-dependent current. AP prolongation with reduction of rapid delayed rectifier
      current (I(Kr)) and I(Ks) (due to mutations or drugs) showed strong species
      dependence in simulations, as in experiments. For humans, AP prolongation was 80%
      following I(Kr) block. It was 30% for dog and 20% for guinea pig. Under basal
      conditions, I(Ks) block was of no consequence for human and dog, but for guinea
      pig, AP prolongation after I(Ks) block was severe. However, with beta-adrenergic
      stimulation, I(Ks) played an important role in all species, particularly in AP
      shortening at fast rate. Quantitative comparison of AP repolarization, rate
      dependence mechanisms, and drug response in human, dog, and guinea pig revealed
      major species differences (e.g., susceptibility to arrhythmogenic early
      afterdepolarizations). Extrapolation from animal to human electrophysiology and
      drug response requires great caution.

PMID- 22159994
TI  - Hypoxia differentially regulates arterial and venous smooth muscle cell
      proliferation via PDGFR-beta and VEGFR-2 expression.
AB  - Despite intensive research studies, theories have yet to focus on the
      contribution of hypoxia to patency differences observed clinically between
      arterial vs. venous grafts. This study investigates the differential hypoxic
      response of smooth muscle cells (SMC) to hypoxia-derived endothelial cell (EC)
      growth factors. Initiation of SMC proliferation under hypoxia (<5% O(2)) occurred
      only after incubation with hypoxic endothelial cell-conditioned media (H-ECM).
      After the investigation of several possible growth factors in the H-ECM that may
      be responsible for SMC proliferation, the greatest difference was observed in
      vascular endothelial growth factor (VEGF-A) and platelet-derived growth factor
      homodimer B (PDGF-BB) expression. VEGF-A increased (2-fold) significantly (P <
      0.05) in arterial-derived smooth muscle cells (ASMC) under hypoxia compared with
      venous-derived smooth muscle cells (VSMC), which showed no significant change.
      VSMC showed significant (P < 0.05) increase in VEGFR-2 expression under hypoxia
      compared with ASMC. Incubation with VEGFR-2-neutralizing antibody/PDGFR
      antagonist in VSMC before addition of H-ECM resulted in decreased proliferation.
      ASMC proliferation under hypoxia did not decrease during incubation with VEGFR-2
      neutralizing antibody but did decrease upon PDGFR antagonist incubation. Current
      therapies focusing on treating intimal hyperplasia have negated the fact that
      combinational therapy might be required to combat induction of SMC proliferation.
      Clinically, therapy with PDGFR antagonists plus anti-VEGFR-2 may prove to be
      efficacious in managing SMC proliferation in venous-derived grafts.

PMID- 22159995
TI  - Prostacyclin receptor-mediated ATP release from erythrocytes requires the voltage
      dependent anion channel.
AB  - Erythrocytes have been implicated as controllers of vascular caliber by virtue of
      their ability to release the vasodilator ATP in response to local physiological
      and pharmacological stimuli. The regulated release of ATP from erythrocytes
      requires activation of a signaling pathway involving G proteins (G(i) or G(s)),
      adenylyl cyclase, protein kinase A, and the cystic fibrosis transmembrane
      conductance regulator as well as a final conduit through which this highly
      charged anion exits the cell. Although pannexin 1 has been shown to be the final
      conduit for ATP release from human erythrocytes in response to reduced oxygen
      tension, it does not participate in transport of ATP following stimulation of the
      prostacyclin (IP) receptor in these cells, which suggests that an additional
      protein must be involved. Using antibodies directed against voltage-dependent
      anion channel (VDAC)1, we confirm that this protein is present in human
      erythrocyte membranes. To address the role of VDAC in ATP release, two
      structurally dissimilar VDAC inhibitors, Bcl-x(L) BH4(4-23) and TRO19622, were
      used. In response to the IP receptor agonists, iloprost and UT-15C, ATP release
      was inhibited by both VDAC inhibitors although neither iloprost-induced cAMP
      accumulation nor total intracellular ATP concentration were altered. Together,
      these findings support the hypothesis that VDAC is the ATP conduit in the IP
      receptor-mediated signaling pathway in human erythrocytes. In addition, neither
      the pannexin inhibitor carbenoxolone nor Bcl-x(L) BH4(4-23) attenuated ATP
      release in response to incubation of erythrocytes with the beta-adrenergic
      receptor agonist isoproterenol, suggesting the presence of yet another channel
      for ATP release from human erythrocytes.

PMID- 22159996
TI  - Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons
      accounts for the pressor effect of ethanol in spontaneously hypertensive rats.
AB  - We have previously shown that ethanol microinjection into the rostral
      ventrolateral medulla (RVLM) elicits sympathoexcitation and hypertension in
      conscious spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY)
      rats. In this study, evidence was sought to implicate the oxidative breakdown of
      ethanol in this strain-dependent hypertensive action of ethanol. Biochemical
      experiments revealed significantly higher catalase activity and similar aldehyde
      dehydrogenase (ALDH) activity in the RVLM of SHRs compared with WKY rats. We also
      investigated the influence of pharmacological inhibition of catalase (3
      aminotriazole) or ALDH (cyanamide) on the cardiovascular effects of intra-RVLM
      ethanol or its metabolic product acetaldehyde in conscious rats. Compared with
      vehicle, ethanol (10 MUg/rat) elicited a significant increase in blood pressure
      in SHRs that lasted for the 60-min observation period but had no effect on blood
      pressure in WKY rats. The first oxidation product, acetaldehyde, played a
      critical role in ethanol-evoked hypertension because 1) catalase inhibition (3
      aminotriazole treatment) virtually abolished the ethanol-evoked pressor response
      in SHRs, 2) intra-RVLM acetaldehyde (2 MUg/rat) reproduced the strain-dependent
      hypertensive effect of intra-RVLM ethanol, and 3) ALDH inhibition (cyanamide
      treatment) uncovered a pressor response to intra-RVLM acetaldehyde in WKY rats
      similar to the response observed in SHRs. These findings support the hypothesis
      that local production of acetaldehyde, due to enhanced catalase activity, in the
      RVLM mediates the ethanol-evoked pressor response in SHRs.

PMID- 22159999
TI  - Ghrelin protects musculocutaneous tissue from ischemic necrosis by improving
      microvascular perfusion.
AB  - Persistent ischemia in musculocutaneous tissue may lead to wound breakdown and
      necrosis. The objective of this experimental study was to analyze, whether the
      gastric peptide ghrelin prevents musculocutaneous tissue from necrosis and to
      elucidate underlying mechanisms. Thirty-two C57BL/6 mice equipped with a dorsal
      skinfold chamber containing ischemic musculocutaneous tissue were allocated to
      four groups: 1) ghrelin; 2) N(omega)-nitro-l-arginine methyl ester (l-NAME); 3)
      ghrelin and l-NAME; and 4) control. Microcirculation, inflammation, angiogenesis,
      and tissue survival were assessed by fluorescence microscopy. Inducible and
      endothelial nitric oxide synthase (iNOS I and eNOS), vascular endothelial growth
      factor (VEGF), as well as nuclear factor kappaB (NF-kappaB) were assessed by
      Western blot analysis. Ghrelin-treated animals showed an increased expression of
      iNOS and eNOS in critically perfused tissue compared with controls. This was
      associated with arteriolar dilation, increased arteriolar perfusion, and a
      sustained functional capillary density. Ghrelin further upregulated NF-kappaB and
      VEGF and induced angiogenesis. Finally, ghrelin reduced microvascular leukocyte
      endothelial cell interactions, apoptosis, and overall tissue necrosis (P < 0.05
      vs. control). Inhibition of nitric oxide by l-NAME did not affect the anti
      inflammatory and angiogenic action of ghrelin but completely blunted the ghrelin
      induced tissue protection by abrogating the arteriolar dilation, the improved
      capillary perfusion, and the increased tissue survival. Ghrelin prevents
      critically perfused tissue from ischemic necrosis. Tissue protection is the
      result of a nitric oxide synthase-mediated improvement of the microcirculation
      but not due to induction of angiogenesis or attenuation of inflammation. This
      might represent a promising, noninvasive, and clinically applicable approach to
      protect musculocutaneous tissue from ischemia.

PMID- 22159998
TI  - Effects of elastin degradation and surrounding matrix support on artery
      stability.
AB  - Tortuous arteries are often associated with aging, hypertension, atherosclerosis,
      and degenerative vascular diseases, but the mechanisms are poorly understood. Our
      recent theoretical analysis suggested that mechanical instability (buckling) may
      lead to tortuous blood vessels. The objectives of this study were to determine
      the critical pressure of artery buckling and the effects of elastin degradation
      and surrounding matrix support on the mechanical stability of arteries. The
      mechanical properties and critical buckling pressures, at which arteries become
      unstable and deform into tortuous shapes, were determined for a group of five
      normal arteries using pressurized inflation and buckling tests. Another group of
      nine porcine arteries were treated with elastase (8 U/ml), and the mechanical
      stiffness and critical pressure were obtained before and after treatment. The
      effect of surrounding tissue support was simulated using a gelatin gel. The
      critical pressures of the five normal arteries were 9.52 kPa (SD 1.53) and 17.10
      kPa (SD 5.11) at axial stretch ratios of 1.3 and 1.5, respectively, while model
      predicted critical pressures were 10.11 kPa (SD 3.12) and 17.86 kPa (SD 5.21),
      respectively. Elastase treatment significantly reduced the critical buckling
      pressure (P < 0.01). Arteries with surrounding matrix support buckled into
      multiple waves at a higher critical pressure. We concluded that artery buckling
      under luminal pressure can be predicted by a buckling equation. Elastin
      degradation weakens the arterial wall and reduces the critical pressure, which
      thus leads to tortuous vessels. These results shed light on the mechanisms of the
      development of tortuous vessels due to elastin deficiency.

PMID- 22159997
TI  - Impairments in the intrinsic contractility of mesenteric collecting lymphatics in
      a rat model of metabolic syndrome.
AB  - Numerous studies on metabolic syndrome (MetSyn), a cluster of metabolic
      abnormalities, have demonstrated its profound impact on cardiovascular and blood
      microvascular health; however, the effects of MetSyn on lymphatic function are
      not well understood. We hypothesized that MetSyn would modulate lymphatic muscle
      activity and alter muscularized lymphatic function similar to the impairment of
      blood vessel function associated with MetSyn, particularly given the direct
      proximity of the lymphatics to the chronically inflamed adipose depots. To test
      this hypothesis, rats were placed on a high-fructose diet (60%) for 7 wk, and
      their progression to MetSyn was assessed through serum insulin and triglyceride
      levels in addition to the expression of metabolic and inflammatory genes in the
      liver. Mesenteric lymphatic vessels were isolated and subjected to different
      transmural pressures while lymphatic pumping and contractile parameters were
      evaluated. Lymphatics from MetSyn rats had significant negative chronotropic
      effects at all pressures that effectively reduced the intrinsic flow-generating
      capacity of these vessels by ~50%. Furthermore, lymphatics were remodeled to a
      significantly smaller diameter in the animals with MetSyn. Wire myograph
      experiments demonstrated that permeabilized lymphatics from the MetSyn group
      exhibited a significant decrease in force generation and were less sensitive to
      Ca(2+), although there were no significant changes in lymphatic muscle cell
      coverage or morphology. Thus, our data provide the first evidence that MetSyn
      induces a remodeling of collecting lymphatics, thereby effectively reducing their
      potential load capabilities and impairing the intrinsic contractility required
      for proper lymph flow.

PMID- 22160000
TI  - Prevention of adverse cardiac remodeling to volume overload in female rats is the
      result of an estrogen-altered mast cell phenotype.
AB  - Previously, we have reported sex differences in the cardiac remodeling response
      to ventricular volume overload whereby male and ovariectomized (OVX) female rats
      develop eccentric hypertrophy, and intact (Int) female rats develop concentric
      hypertrophy. In males, this adverse remodeling has been attributed to an initial
      cascade of events involving myocardial mast cell and matrix metalloproteinase
      activation and extracellular collagen matrix degradation. The objective of this
      study was to determine the effect of female hormones on this initial cascade.
      Accordingly, an aortocaval fistula (Fist) was created in 7-wk-old Int and OVX
      rats, which, together with sham-operated (sham) controls, were studied at 1, 3,
      and 5 days postsurgery. In Int-Fist rats, myocardial mast cell density, collagen
      volume fraction, endothelin (ET)-1, stem cell factor (SCF), and TNF-alpha
      remained at control levels or were minimally elevated throughout the study
      period. This was not the case in the OVX-Fist group, where the initial response
      included significant increases in mast cell density, collagen degradation, ET-1,
      SCF, and TNF-alpha. These events in the OVX-Fist group were abolished by
      prefistula treatment with a mast cell stabilizer nedocromil. Of note was the
      observation that ET-1, TNF-alpha, SCF, and collagen volume fraction values for
      the OVX-sham group were greater than those of the Int-sham group, suggesting that
      the reduction of female hormones alone results in major myocardial changes. We
      concluded that female hormone-related cardioprotection to the volume stressed
      myocardium is the result of an altered mast cell phenotype and/or the prevention
      of mast cell activation.

PMID- 22160001
TI  - Calixarene-induced aggregation of perylene bisimides.
AB  - The complex-induced aggregation of perylene bisimides by p
      sulfonatocalix[n]arenes was studied, where the aggregation stability, aggregation
      distance, as well as the degree of order of aggregation were all improved.

PMID- 22160002
TI  - Adenosine A2A receptor contributes to the anti-inflammatory effect of the fixed
      herbal combination STW 5 (Iberogast(r)) in rat small intestinal preparations.
AB  - STW 5 (Iberogast(r)), an established herbal combination, was effective in
      randomized, double blind clinical studies in functional dyspepsia and irritable
      bowel syndrome. Since STW 5 was found to influence intestinal motility and has
      anti-inflammatory properties, this study investigated the expression of adenosine
      receptors and characterized their role in the control of the anti-inflammatory
      action of STW 5 and its fresh plant component STW 6 in inflammation-disturbed rat
      small intestinal preparations. The inflammation was induced by intraluminal
      instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 0.01 M). The effects
      of coincubation with selective receptor agonists and antagonists, STW 5, STW 6,
      or combinations of these compounds on acetylcholine (ACh)-evoked contraction of
      ileum/jejunum preparations were tested. Adenosine receptor mRNA expression was
      examined by reverse transcription-polymerase chain reaction (RT-PCR). In
      untreated preparations, RT-PCR revealed the presence of all adenosine receptor
      subtypes. Suppressed expression was detected for all subtypes in inflamed
      tissues, except for A(2B)R mRNA, which was unaffected. STW 5 reversed these
      effects and enhanced A(2A)R expression above control levels. Radioligand binding
      assays confirm the affinity of STW 5 to the A(2A)R, and the A(2A)R antagonist was
      able to prevent the effect of STW 5 on TNBS-induced attenuation of the ACh
      contraction. Our findings provide evidence that STW 5, but not STW 6 interacts
      with A(2A)R, which is involved in the anti-inflammatory action of STW 5. STW 6
      did not contribute to adenosine A(2A)R-mediated anti-inflammatory effect of STW
      5. Other signaling pathways could be involved in the mechanism of action of STW
      6.

PMID- 22160003
TI  - Prevalence of overweight, obesity, and associated risk factors among school
      children and adolescents in Tianjin, China.
AB  - To estimate the prevalence and determinants of overweight and obesity among
      school children and adolescents (7-18 years), a cross-sectional study was
      conducted in Tianjin City of Northeast China. Five primary and middle schools
      were selected using a multistage random cluster sampling. Anthropometric
      measurements were taken by the research team. Then, standardized questionnaires
      on socioeconomic status, diet and lifestyle, parental weight and height were sent
      to the parents to be completed together with their child. Overall, 3,140 students
      were screened for overweight and associated risk factors. Body mass index
      classification reference proposed by the Working Group on Obesity in China was
      used as a screening reference to calculate the prevalence of overweight in these
      groups. The prevalence of overweight and obesity was found to be 12.5% and 15.7%,
      respectively. Logistic regression analysis (overweight compared with normal
      weight) showed that, overweight in children was significantly associated with
      male gender, parental obesity, parental educational level, mother's history of
      gestational diabetes, high birth weight, less hours of physical activity per day,
      urban residence, motorized transportation, and eating food not prepared at home.
      After adjusting for parental obesity, the odds ratio of overweight children was
      increased by urban residence (rural as a reference, 2.68, 2.16-3.32), positive
      gestational diabetes (2.76, 1.37-4.50), and fast-food/restaurant food service
      (2.03, 1.34-3.07). Children who walked to school and participated in outdoor
      activities were 54% and 63% less likely to be overweight respectively.
      CONCLUSIONS: The prevalence of overweight and obesity is high among school
      children and adolescents in Tianjin. Changes in lifestyle, high socioeconomic
      status, parental obesity, mother's history of gestational diabetes, and high
      birth weight are among the highly associated risk factors of overweight. An
      educational approach about maintaining a healthy weight should be introduced much
      earlier to high-risk children, parents, and women of childbearing age.

PMID- 22160004
TI  - Gilbert syndrome.
AB  - Gilbert syndrome is a common autosomal dominant hereditary condition with
      incomplete penetrance and characterized by intermittent unconjugated
      hyperbilirubinemia in the absence of hepatocellular disease or hemolysis. In
      patients with Gilbert syndrome, uridine diphosphate-glucuronyl transferase
      activity is reduced to 30% of the normal, resulting in indirect
      hyperbilirubinemia. In its typical form, hyperbilirubinemia is first noticed as
      intermittent mild jaundice in adolescence. However, Gilbert syndrome in
      combination with other prevailing conditions such as breast feeding, G-6-PD
      deficiency, thalassemia, spherocytosis, or cystic fibrosis may potentiate severe
      hyperbilirubinemia and/or cholelithiasis. It may also reduce plasma oxidation,
      and it may also affect drug metabolism. Although in general the diagnosis of the
      syndrome is one of exclusion, molecular genetic tests can now be performed when
      there is a diagnostic problem. The most common genotype of Gilbert syndrome is
      the homozygous polymorphism A(TA)7TAA in the promoter of the gene for UDP
      glucuronosyltransferase 1A1 (UGT1A1), which is a TA insertion into the promoter
      designated UGT1A1*28. No specific management is necessary as Gilbert syndrome is
      a benign condition. CONCLUSION: Gilbert genotype should be kept in the
      clinician's mind, at least as a contributor factor, in cases with unexplained
      indirect hyperbilirubinemia.

PMID- 22160005
TI  - Angiogenesis: a target in solid tumors, also in leukemia?
AB  - Targeting angiogenesis has become an established therapeutic approach to fighting
      solid tumor growth in cancer patients. Even though increased angiogenesis has
      long been recognized in various types of hematologic malignancies, the molecular
      basis underlying this angiogenic switch in leukemias remains poorly understood.
      The BM stroma is gaining increasing attention for its role in promoting leukemia
      growth and resistance against current treatments with tyrosine kinase inhibitors.
      This article provides a brief overview of the role of angiogenesis in leukemias,
      discusses recent insights into the role of placenta growth factor (PlGF), a VEGF
      family member, as a novel disease candidate in chronic myeloid leukemia (CML),
      and highlights the therapeutic potential of PlGF blockade for imatinib-resistant
      CML.

PMID- 22160006
TI  - Too much of a good thing at the site of tissue injury: the instructive example of
      the complement system predisposing to thrombotic microangiopathy.
AB  - The interplay between the complement and coagulation systems is just beginning to
      be explored and characterized. This interaction, however, is ancient. For
      example, if endotoxin is added to the hemolymph of the horseshoe crab, a protease
      is activated that triggers both the coagulation and complement systems. However,
      in extant mammals, these 2 cascades have diverged. These infamous "terrible C's"
      are the scourge of many a medical student (and possibly even a few
      hematologists). They also are intimately involved in the pathophysiology of
      thrombomicroangiopathies (TMAs). The complement system generates a procoagulant
      microenvironment and the coagulation system forms a clot in the renal
      microvasculature, and thus the 2 systems are partners in mediating multiple
      pathophysiological conditions.

PMID- 22160007
TI  - Atypical hemolytic uremic syndrome, genetic basis, and clinical manifestations.
AB  - Atypical hemolytic uremic syndrome (aHUS) is now well recognized to be a disease
      characterized by excessive complement activation in the microvasculature. In both
      the familial and sporadic forms, inherited and acquired abnormalities affecting
      components of the alternative complement pathway are found in ~ 60% of patients.
      These include mutations in the genes encoding both complement regulators (factor
      H, factor I, membrane cofactor protein, and thrombomodulin) and activators
      (factors B and C3) and autoantibodies against factor H. Multiple hits are
      necessary for the disease to manifest, including a trigger, mutations, and at
      risk haplotypes in complement genes. The prognosis for aHUS is poor, with most
      patients developing end-stage renal failure. Renal transplantation in most
      patients also has a poor prognosis, with frequent loss of the allograft to
      recurrent disease. However, improving results with combined liver-kidney
      transplantation and the advent of complement inhibitors such as eculizumab offer
      hope that the prognosis for aHUS will improve in future years.

PMID- 22160008
TI  - Management of paroxysmal nocturnal hemoglobinuria in the era of complement
      inhibitory therapy.
AB  - Despite the availability of safe, effective targeted therapy that controls
      intravascular hemolysis, the management of paroxysmal nocturnal hemoglobinuria
      (PNH) remains complicated because of disease heterogeneity and close association
      with BM failure syndromes. The purpose of this review is to provide a framework
      for individualizing treatment based on disease classification. According to the
      recommendations of the International PNH Interest Group, patients can be placed
      into one of the following 3 categories: (1) classic PNH, (2) PNH in the setting
      of another BM failure syndrome, or (3) subclinical PNH. The PNH clone in patients
      with subclinical disease is insufficiently large to produce even biochemical
      evidence of hemolysis, and consequently, patients who fit into this category
      require no PNH-specific therapy. Patients with PNH in the setting of another BM
      failure syndrome (usually aplastic anemia or low-risk myelodysplastic syndrome)
      have at least biochemical evidence of hemolysis, but typically the PNH clone is
      small (< 10%) so that hemolysis does not contribute significantly to the
      underlying anemia. In these cases, the focus of treatment is on the BM failure
      component of the disease. Intravascular hemolysis is the dominant feature of
      classic PNH, and this process is blocked by the complement inhibitor eculizumab.
      The thrombophilia of PNH also appears to be ameliorated by eculizumab, but the
      drug has no effect on the BM failure component of the disease. Low-grade
      extravascular hemolysis due to complement C3 opsonization develops in most
      patients treated with eculizumab, and in some cases is a cause for suboptimal
      response to treatment. Allogeneic BM transplantation can cure classic PNH, but
      treatment-related toxicity suggests caution for this approach to management.

PMID- 22160009
TI  - Genomics of AML: clinical applications of next-generation sequencing.
AB  - In the past decade, a series of technological advances have revolutionized our
      ability to interrogate cancer genomes, culminating in whole-genome sequencing,
      which provides genome-wide coverage at a single base-pair resolution. As
      sequencing technologies improve and costs decrease, it is likely that whole
      genome sequencing of cancer cells will become commonplace in the diagnostic
      workup of patients with acute myelogenous leukemia (AML) and other cancers. The
      unprecedented molecular characterization provided by whole-genome sequencing
      offers the potential for an individualized approach to treatment in AML, bringing
      us one step closer to personalized medicine. In this chapter, we discuss how next
      generation sequencing is being used to study cancer genomes. Recent publications
      of whole-genome sequencing in AML are reviewed and current limitations of whole
      genome sequencing are examined, as well as current and potential future clinical
      applications of whole-genome sequencing.

PMID- 22160010
TI  - Impact of genetic features on treatment decisions in AML.
AB  - In recent years, research in molecular genetics has been instrumental in
      deciphering the molecular pathogenesis of acute myeloid leukemia (AML). With the
      advent of the novel genomics technologies such as next-generation sequencing, it
      is expected that virtually all genetic lesions in AML will soon be identified.
      Gene mutations or deregulated expression of genes or sets of genes now allow us
      to explore the enormous diversity among cytogenetically defined subsets of AML,
      in particular the large subset of cytogenetically normal AML. Nonetheless, there
      are several challenges, such as discriminating driver from passenger mutations,
      evaluating the prognostic and predictive value of a specific mutation in the
      concert of the various concurrent mutations, or translating findings from
      molecular disease pathogenesis into novel therapies. Progress is unlikely to be
      fast in developing molecular targeted therapies. Contrary to the initial
      assumption, the development of molecular targeted therapies is slow and the
      various reports of promising new compounds will need to be put into perspective
      because many of these drugs did not show the expected effects.

PMID- 22160011
TI  - Novel approaches to the treatment of acute myeloid leukemia.
AB  - Approximately 12 000 adults are diagnosed with acute myeloid leukemia (AML) in
      the United States annually, the majority of whom die from their disease. The
      mainstay of initial treatment, cytosine arabinoside (ara-C) combined with an
      anthracycline, was developed nearly 40 years ago and remains the worldwide
      standard of care. Advances in genomics technologies have identified AML as a
      genetically heterogeneous disease, and many patients can now be categorized into
      clinicopathologic subgroups on the basis of their underlying molecular genetic
      defects. It is hoped that enhanced specificity of diagnostic classification will
      result in more effective application of targeted agents and the ability to create
      individualized treatment strategies. This review describes the current treatment
      standards for induction, consolidation, and stem cell transplantation; special
      considerations in the management of older AML patients; novel agents; emerging
      data on the detection and management of minimal residual disease (MRD); and
      strategies to improve the design and implementation of AML clinical trials.

PMID- 22160012
TI  - The role of platelets in atherothrombosis.
AB  - Platelets have evolved highly specialized adhesion mechanisms that enable cell
      matrix and cell-cell interactions throughout the entire vasculature irrespective
      of the prevailing hemodynamic conditions. This unique property of platelets is
      critical for their ability to arrest bleeding and promote vessel repair. Platelet
      adhesion under conditions of high shear stress, as occurs in stenotic
      atherosclerotic arteries, is central to the development of arterial thrombosis;
      therefore, precise control of platelet adhesion must occur to maintain blood
      fluidity and to prevent thrombotic or hemorrhagic complications. Whereas the
      central role of platelets in hemostasis and thrombosis has long been recognized
      and well defined, there is now a major body of evidence supporting an important
      proinflammatory function for platelets that is linked to host defense and a
      variety of autoimmune and inflammatory diseases. In the context of the
      vasculature, experimental evidence indicates that the proinflammatory function of
      platelets can regulate various aspects of the atherosclerotic process, including
      its initiation and propagation. The mechanisms underlying the proatherogenic
      function of platelets are increasingly well defined and involve specific adhesive
      interactions between platelets and endothelial cells at atherosclerotic-prone
      sites, leading to the enhanced recruitment and activation of leukocytes. Through
      the release of chemokines, proinflammatory molecules, and other biological
      response modulators, the interaction among platelets, endothelial cells, and
      leukocytes establishes a localized inflammatory response that accelerates
      atherosclerosis. These inflammatory processes typically occur in regions of the
      vasculature experiencing low shear and perturbed blood flow, a permissive
      environment for leukocyte-platelet and leukocyte-endothelial interactions.
      Therefore, the concept has emerged that platelets are a central element of the
      atherothrombotic process and that future therapeutic strategies to combat this
      disease need to take into consideration both the prothrombotic and
      proinflammatory function of platelets.

PMID- 22160013
TI  - Advances in antiplatelet therapy.
AB  - Because of the central role of platelets in cardiovascular atherothrombosis,
      there is a well-established therapeutic role for antiplatelet therapy that
      includes aspirin (a cyclooxygenase 1 [COX1] inhibitor), clopidogrel (an
      antagonist of the ADP P2Y(12) receptor), and the GPIIb-GPIIIa (alphaIIbbeta3)
      antagonists. However, there remains a significant incidence of arterial
      thrombosis in patients treated with currently available antiplatelet therapy.
      Novel P2Y(12) antagonists such as the recently US Food and Drug Administration
      (FDA)-approved prasugrel, along with ticagrelor, cangrelor, and elinogrel, have
      advantages over clopidogrel, including more rapid, less variable, and more
      complete inhibition of platelet function. Currently ongoing phase 3 studies will
      determine whether these new P2Y(12) antagonists will result in better and/or more
      rapid antithrombotic effects than clopidogrel, without an unacceptable increase
      in hemorrhagic or other side effects, as has been recently reported in some
      clinical settings for prasugrel and ticagrelor. Antagonists of the thrombin
      receptor protease-activated receptor 1 (PAR1) are also undergoing phase 3 trials,
      and many other novel antiplatelet agents are under investigation as
      antithrombotic agents.

PMID- 22160014
TI  - The clinical relevance of response variability to antiplatelet therapy.
AB  - Interindividual variability in the pharmacological response to antiplatelet drugs
      has been reported in some studies. Suboptimal response to aspirin, as determined
      by specific tests (serum thromboxane B(2)), appears to be rare and in most cases
      is caused by poor compliance. In contrast, studies using specific tests to
      measure the pharmacological effect of clopidogrel showed a wide variability of
      responses, with a significant number of subjects (approximately one-third) who
      were very poor responders. Interindividual differences in the extent of
      metabolism of clopidogrel to its active metabolite is the most plausible
      mechanism for the observed interindividual variability in platelet inhibition.
      Tailored treatment based on laboratory monitoring of platelet function has been
      proposed as a solution to poor responsiveness to clopidogrel. However, we still
      need to identify the ideal laboratory test and to answer basic questions on its
      clinical utility and cost-effectiveness before monitoring clopidogrel therapy can
      be recommended in clinical practice.

PMID- 22160015
TI  - Diagnosis and management of aplastic anemia.
AB  - Aplastic anemia remains a diagnosis of exclusion. Our ability to reliably
      diagnose, and therefore exclude, a variety of inherited or acquired diseases with
      similar phenotypes has improved markedly. An efficient diagnostic plan is
      important because time from diagnosis to treatment is related to outcome
      regardless of the therapeutic option chosen. HSCT remains the mainstay of therapy
      for those with matched sibling donors, and results have improved even further in
      recent years. For those without a sibling donor, the high response and overall
      survival rates of combined immunosuppressive therapy (IST) have proven robust.
      Nonetheless, incomplete response, relapse, and progression to
      myelodysplasia/leukemia have more clearly emerged as significant long-term
      issues. Improvements in outcome of alternative donor transplantation and the use
      of established and novel immunosuppressive agents provide multiple alternatives
      for treating refractory or relapsed patients. Best practices in this regard are
      not yet clearly established and may vary by a variety of demographic and
      treatment-specific factors. Regardless of the type of therapeutic approach,
      patients require ongoing monitoring for occurrence of disease and/or therapy
      related side effects.

PMID- 22160016
TI  - Therapy for aplastic anemia.
AB  - A 24-year-old man from Ecuador presents to your clinic with dyspnea on exertion,
      bruising, and petechiae. He is noted to be pancytopenic with ANC 430, hemoglobin
      7.4 g/dL (reticulocyte count 0.9%), and platelets 18 000. His BM biopsy is
      hypocellular for age. Ultimately, he is diagnosed with severe aplastic anemia. He
      is the only child of 2 South American parents without any matches in the
      unrelated donor registry, including cord blood. He is red cell- and platelet
      transfusion-dependent. He has been recommended therapy with antithymocyte
      globulin and cyclosporine but declined it. He seeks recommendations about new
      alternatives to this regimen to improve his chance of response.

PMID- 22160017
TI  - Classification of childhood aplastic anemia and myelodysplastic syndrome.
AB  - Hypoplastic BM disorders in children and adolescents comprise a broad spectrum of
      disorders. Acquired severe aplastic anemia (SAA), refractory cytopenia of
      childhood (RCC), a subtype of myelodysplastic syndrome (MDS), and inherited BM
      failure (IBMF) disorders are the main and most difficult hematological
      differential diagnoses. Whereas IBMF disorders can often be diagnosed by their
      clinical features and/or underlying genetic aberrations, the morphological
      distinction between SAA and hypocellular RCC has been controversial. The
      histopathological pattern of RCC consists of islands of immature erythroid
      precursors accompanied by sparsely distributed granulocytic cells. Megakaryocytes
      are significantly decreased or absent and, rarely, micromegakaryocytes are
      detected on immunohistochemistry. Because fatty tissue between areas of
      hematopoiesis can mimic SAA, 2 biopsies are recommended to facilitate the
      detection of representative BM spaces. Recent data indicate that the response to
      immunosuppressive therapy is inferior in RCC compared with SAA. Furthermore,
      approaches to allogeneic hematopoietic transplantation differ. Controlled
      prospective clinical studies in patients with hypoplastic BM failure disorders
      will require comprehensive guidelines for diagnosing SAA, RCC, and the different
      IBMF disorders.

PMID- 22160018
TI  - Clonal evolution in aplastic anemia.
AB  - Current immunosuppressive treatment (IST) induces remissions in 50%-70% of
      patients with aplastic anemia (AA) and result in excellent long-term survival. In
      recent years, the survival of refractory patients has also improved. Apart from
      relapse and refractoriness to IST, evolution of clonal diseases, including
      paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome (MDS), are the
      most serious long-term complications and constitute a strong argument for
      definitive therapy with BM transplantation if possible. Consequently, the
      detection of diagnostic chromosomal abnormalities (mostly monosomy 7) is of great
      clinical importance. Newer whole-genome scanning technologies such as single
      nucleotide polymorphism (SNP) array-based karyotyping may be a helpful diagnostic
      test for the detection of chromosomal defects in AA due to its
      precision/resolution and lack of reliance on cell division.

PMID- 22160019
TI  - Nurture versus nature: the microenvironment in chronic lymphocytic leukemia.
AB  - Intrinsic factors such as genetic lesions, anti-apoptotic proteins, and aberrant
      signaling networks within leukemia cells have long been the main focus of chronic
      lymphocytic leukemia (CLL) research. However, over the past decade, it became
      increasingly clear that external signals from the leukemia microenvironment make
      pivotal contributions to disease progression in CLL and other B-cell
      malignancies. Consequently, increasing emphasis is now placed on exploring and
      targeting the CLL microenvironment. This review highlights critical cellular and
      molecular pathways of CLL-microenvironment cross-talk. In vitro and in vivo
      models for studying the CLL microenvironment are discussed, along with their use
      in searching for therapeutic targets and in drug testing. Clinically, CXCR4
      antagonists and small-molecule antagonists of B cell receptor (BCR)-associated
      kinases (spleen tyrosine kinase [Syk], Bruton's tyrosine kinase [Btk], and
      PI3Kdelta) are the most advanced drugs for targeting specific interactions
      between CLL cells and the miocroenvironment. Preclinical and first clinical
      evidence suggests that high-risk CLL patients can particularly benefit from these
      alternative agents. These findings indicate that interplay between leukemia
      inherent and environmental factors, nature and nurture determines disease
      progression in CLL.

PMID- 22160020
TI  - Using the biology of chronic lymphocytic leukemia to choose treatment.
AB  - In recent years, our understanding of the pathophysiology of chronic lymphocytic
      leukemia (CLL) has advanced significantly. It is now clear that CLL is a
      relatively proliferative disorder that requires the help of its microenvironment
      to be maintained and to progress. The stimulation of the CLL cell occurs in most,
      if not all, patients through antigen stimulation via the BCR. In addition, there
      is now a clearer appreciation of the role of the p53 pathway leading to
      chemoresistance. These insights are allowing a more targeted approach with the
      use of p53-independent drugs such as mAbs and high-dose steroids to overcome
      genetically poor-risk CLL. The elucidation of the molecular and intracellular
      signaling mechanisms of disease is just beginning to facilitate the development
      of several targeted small molecules that promise to revolutionize the treatment
      of CLL. The measurement of the level of minimal residual disease (MRD) in CLL is
      becoming more available, facilitating approaches in which the aim of therapy is
      the eradication of detectable MRD. This also promises to improve personalization
      of therapy to the individual. Recently, the addition of rituximab to fludarabine
      plus cyclophosphamide (FCR) has improved overall survival in CLL for the first
      time, and it appears that this will only be the first small step on the path to
      much more effective therapies and, hopefully, less toxic targeted therapies.

PMID- 22160021
TI  - The treatment of relapsed refractory chronic lymphocytic leukemia.
AB  - Despite the widespread use of highly effective chemoimmunotherapy (CIT),
      fludarabine-refractory chronic lymphocytic leukemia (CLL) remains a challenging
      clinical problem associated with poor overall survival (OS). The traditional
      definition, which includes those patients with no response or relapse within 6
      months of fludarabine, is evolving with the recognition that even patients with
      longer remissions of up to several years after CIT have poor subsequent treatment
      response and survival. Approved therapeutic options for these patients remain
      limited, and the goal of therapy for physically fit patients is often to achieve
      adequate cytoreduction to proceed to allogeneic stem cell transplantation
      (alloSCT). Fortunately, several novel targeted therapeutics in clinical trials
      hold promise of significant benefit for this patient population. This review
      discusses the activity of available and novel therapeutics in fludarabine
      refractory or fludarabine-resistant CLL as well as recently updated data on
      alloSCT in CLL.

PMID- 22160022
TI  - Alemtuzumab use in relapsed and refractory chronic lymphocytic leukemia.
      [corrected].
AB  - A 62-year-old woman with chronic lymphocytic leukemia [corrected] (CLL) who
      initially presented with lymphocytosis and 13q deletion in 1996 now presents to
      the clinic for recommendations regarding relapsed disease. The patient has
      received multiple prior therapies, including single-agent fludarabine,
      fludarabine and rituximab, and bendamustine and rituximab. She now has recurrent
      lymphocytosis with a WBC count that has increased from 13,000 2 months ago to
      115,000 today and a platelet count of 55,000 but no lymphadenopathy. In addition,
      your evaluation finds that she has acquired a 17p deletion.

PMID- 22160023
TI  - Tyrosine kinase inhibitor therapy for chronic myeloid leukemia: approach to
      patients with treatment-naive or refractory chronic-phase disease.
AB  - The 21st century ushered in the dawn of a new era of targeted therapeutics and a
      dramatic shift in the management of chronic-phase chronic myeloid leukemia (CP
      CML) patients. Groundbreaking scientific and translational studies have led to
      the rapid development and approval of several effective BCR-ABL tyrosine kinase
      inhibitors (TKIs). In the United States, there are currently 3 approved BCR-ABL
      TKIs for newly diagnosed CP-CML patients. It is anticipated that clinical
      outcomes will continue to improve as more TKIs that address unmet medical needs
      are approved. However, to achieve this goal, it is critical to carefully monitor
      and optimally manage patients. To this end, the latest seminal clinical trial
      results of approved and investigational BCR-ABL TKIs and some of the salient
      unique features of each of these agents are summarized herein.

PMID- 22160024
TI  - Educational session: managing chronic myeloid leukemia as a chronic disease.
AB  - Elucidation of the pathogenesis of chronic myeloid leukemia (CML) and the
      introduction of tyrosine kinase inhibitors (TKIs) has transformed this disease
      from being invariably fatal to being the type of leukemia with the best
      prognosis. Median survival associated with CML is estimated at > 20 years.
      Nevertheless, blast crisis occurs at an incidence of 1%-2% per year, and once
      this has occurred, treatment options are limited and survival is short. Due to
      the overall therapeutic success, the prevalence of CML is gradually increasing.
      The optimal management of this disease includes access to modern therapies and
      standardized surveillance methods for all patients, which will certainly create
      challenges. Furthermore, all available TKIs show mild but frequent side effects
      that may require symptomatic therapy. Adherence to therapy is the key
      prerequisite for efficacy of the drugs and for long-term success. Comprehensive
      information on the nature of the disease and the need for the continuous
      treatment using the appropriate dosages and timely information on efficacy data
      are key factors for optimal compliance. Standardized laboratory methods are
      required to provide optimal surveillance according to current recommendations.
      CML occurs in all age groups. Despite a median age of 55-60 years, particular
      challenges are the management of the disease in children, young women with the
      wish to get pregnant, and older patients. The main challenges in the long-term
      management of CML patients are discussed in this review.

PMID- 22160025
TI  - Minimal residual disease and discontinuation of therapy in chronic myeloid
      leukemia: can we aim at a cure?
AB  - Patients with chronic myeloid leukemia (CML) who have achieved a complete
      molecular response (CMR) defined by no detectable BCR-ABL mRNA on imatinib (IM)
      treatment often ask whether it is necessary for treatment to continue. We now
      know that approximately 40% of patients with a stable CMR for at least 2 years
      are able to stop IM treatment and remain in molecular remission for at least 2
      years. This exciting observation has raised hopes that many patients can be cured
      of CML without the need for transplantation and its attendant risks. One might
      argue that for many patients maintenance therapy with IM or an alternative kinase
      inhibitor is so well tolerated that there is no imperative to stop treatment;
      however, chronic medical therapy may be associated with impaired quality of life
      and reduced compliance. Inferences about the biology of CML in patients
      responding to kinase inhibitors can be drawn from clinical experience, molecular
      monitoring data, and experimental observations. We summarize this information
      herein, and propose 3 possible pathways to "cure" of CML by kinase inhibitors:
      stem-cell depletion, stem-cell exhaustion, and immunological control.

PMID- 22160026
TI  - How I diagnose and manage HIT.
AB  - Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by
      platelet-activating IgG antibodies that recognize platelet factor 4
      (PF4)/polyanion complexes. Platelet activation assays, such as the serotonin
      release assay, are superior to PF4-dependent immunoassays in discerning which
      heparin-induced antibodies are clinically relevant. When HIT is strongly
      suspected, standard practice includes substituting heparin with an alternative
      anticoagulant; the 2 US-approved agents are the direct thrombin inhibitors (DTIs)
      lepirudin and argatroban, which are "niche" agents used only to manage HIT.
      However, only ~ 10% of patients who undergo serological investigation for HIT
      actually have this diagnosis. Indeed, depending on the clinical setting, only 10%
      50% of patients with positive PF4-dependent immunoassays have platelet-activating
      antibodies. Therefore, overdiagnosis of HIT can be minimized by insisting that a
      positive platelet activation assay be required for definitive diagnosis of HIT.
      For these reasons, a management strategy that considers the real possibility of
      non-HIT thrombocytopenia is warranted. One approach that I suggest is to
      administer an indirect, antithrombin (AT)-dependent factor Xa inhibitor
      (danaparoid or fondaparinux) based upon the following rationale: (1)
      effectiveness in treating and preventing HIT-associated thrombosis; (2)
      effectiveness in treating and preventing thrombosis in diverse non-HIT
      situations; (3) both prophylactic- and therapeutic-dose protocols exist,
      permitting dosing appropriate for the clinical situation; (4) body weight
      adjusted dosing protocols and availability of specific anti-factor Xa monitoring
      reduce risk of under- or overdosing (as can occur with partial thromboplastin
      time [PTT]-adjusted DTI therapy); (5) their long half-lives reduce risk of
      rebound hypercoagulability; (6) easy coumarin overlap; and (7) relatively low
      cost.

PMID- 22160027
TI  - Is thrombophilia testing useful?
AB  - Thrombophilia is found in many patients presenting with venous thromboembolism
      (VTE). However, whether the results of such tests help in the clinical management
      of such patients has not been determined. Thrombophilia testing in asymptomatic
      relatives may be useful in families with antithrombin, protein C, or protein S
      deficiency or homozygosity for factor V Leiden, but is limited to women who
      intend to become pregnant or who would like to use oral contraceptives. Careful
      counseling with knowledge of absolute risks helps patients in making an informed
      decision in which their own preferences can be taken into account. Observational
      studies show that patients who have had VTE and have thrombophilia are at most at
      a slightly increased risk for recurrence. In an observational study, the risk of
      recurrent VTE in patients who had been tested for inherited thrombophilia was not
      lower than in patients who had not been tested. In the absence of trials
      comparing routine and prolonged anticoagulant treatment in patients testing
      positive for thrombophilia, testing for such defects to prolong anticoagulant
      therapy cannot be justified. Diagnosing antiphospholipid syndrome (APS) in women
      with recurrent miscarriage usually leads to treatment with aspirin and low
      molecular-weight heparin (LMWH), although the evidence to support this treatment
      is limited. Because testing for thrombophilia serves a limited purpose, this test
      should not be performed on a routine basis.

PMID- 22160028
TI  - Endovascular procedures in the management of DVT.
AB  - The post-thrombotic syndrome (PTS) develops in 25%-50% of patients with proximal
      lower extremity deep vein thrombosis (DVT) despite the use of standard
      anticoagulant therapy and elastic compression stockings. PTS is a major cause of
      quality of life impairment in DVT patients and often leads to limiting venous
      claudication, work disability, and venous ulcers. Endovascular thrombolytic
      procedures that eliminate venous thrombus, restore venous flow, and show strong
      potential to prevent PTS are now under study in multicenter randomized clinical
      trials. In addition, endovascular procedures can be used to treat valvular reflux
      and venous obstruction and thereby provide symptom improvement to patients with
      chronic established PTS.

PMID- 22160029
TI  - Heparin-induced thrombocytopenia screening and management in pediatric patients.
AB  - The diagnosis and management of heparin-induced thrombocytopenia (HIT) in
      pediatric patients poses significant challenges. The cardinal findings in HIT,
      thrombocytopenia and thrombosis with heparin exposure, are seen commonly in
      critically ill children, but are most often secondary to etiologies other than
      HIT. However, without prompt diagnosis, discontinuation of heparin, and treatment
      with an alternative anticoagulant such as a direct thrombin inhibitor (DTI), HIT
      can result in life- and limb-threatening thrombotic complications. Conversely,
      DTIs are associated with higher bleeding risks than heparin in adults and their
      anticoagulant effects are not rapidly reversible; furthermore, the experience
      with their use in pediatrics is limited. Whereas immunoassays are widely
      available to aid in diagnosis, they carry a significant false positive rate. Age
      dependent differences in the coagulation and immune system may potentially affect
      manifestations of HIT in children, but have not been extensively examined. In
      this chapter, diagnostic approaches and management strategies based on a
      synthesis of the available pediatric studies and adult literature on HIT are
      discussed.

PMID- 22160030
TI  - Bleeding and clotting disorders in pediatric liver disease.
AB  - The coagulopathy of liver disease in pediatric patients presents an unusual set
      of challenges. Little pediatric data have been published, so this review is based
      largely on adult studies. There is a precarious balance between deficiencies of
      clotting factors and anticoagulation factors in liver disease that result in
      abnormal prothrombin time (PT) and activated partial thromboplastin time (aPTT)
      tests that would suggest a bleeding tendency, yet the patients can form a clot
      and are at risk of thromboembolic disease. Attention has centered on
      thromboelastography and thrombin-generation assays to clarify the patient's
      ability to control bleeding, but these tests are not routinely available to many
      treating physicians.

PMID- 22160031
TI  - Approach to hemophagocytic syndromes.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory
      condition. It may occur as a primary (genetic) condition due to mutations in
      genes important in the cytolytic secretory pathway that cause perforin and
      granzymes to induce apoptosis in target cells. Primary HLH is divided into
      familial HLH (FHLH1-5), in which HLH is the only manifestation of disease, and
      other genetic causes in which HLH is one of several clinical manifestations. The
      identical clinical findings may arise secondary to infectious, rheumatologic,
      malignant, or metabolic conditions. Whether primary or secondary, HLH therapy
      needs to be instituted promptly to prevent irreversible tissue damage. It is
      helpful to think of HLH as the severe end of the spectrum of hyperinflammatory
      disorders when the immune system starts to damage host tissues (immunopathology).
      Therefore, no single clinical feature alone is diagnostic for HLH, and it is
      important that the entire clinical presentation be considered in making the
      diagnosis. This article contains a discussion of the genetic background, clinical
      presentation, diagnostic dilemmas, and features that are helpful in making the
      diagnosis of HLH, along with a discussion of common problems in its management.

PMID- 22160032
TI  - New insights into therapeutic targets in myeloma.
AB  - Patient outcome in multiple myeloma (MM) has been remarkably improved due to the
      use of combination therapies including proteasome inhibitors and immunomodulatory
      drugs, which target the tumor in its BM microenvironment. Ongoing efforts to
      improve the treatment paradigm even further include using oncogenomics to better
      characterize molecular pathogenesis and to develop refined patient stratification
      and personalized medicine in MM; using models of MM in its BM milieu to identify
      novel targets and to validate next-generation therapeutics directed at these
      targets; developing immune-based therapies including mAbs, immunotoxins targeting
      MM cells and cytokines, and novel vaccine strategies; and using functional
      oncogenomics to inform the design of novel combination therapies. With continued
      rapid evolution of progress in these areas, MM will be a chronic illness with
      sustained complete response in a significant number of patients.

PMID- 22160033
TI  - Stem cell transplantation for multiple myeloma: current and future status.
AB  - High-dose melphalan with autologous stem cell support has been an integral part
      of myeloma therapy for more than 25 years, either as salvage therapy or as
      consolidation of an initial remission. Although multiple phase 3 trials have
      demonstrated that this therapy results in higher response rates and longer
      remission times than conventional chemotherapy, the use of thalidomide,
      lenalidomide, and bortezomib as induction therapy has limited the clinical
      relevance of these trials. Moreover, ongoing trials have shown that initial
      induction therapy may affect transplantation outcome, and that long-term disease
      control can be achieved in a substantial number of patients with a variety of
      posttransplantation maintenance therapies. This article summarizes the results of
      ongoing and recently published clinical trials and describes how they have
      affected current transplantation recommendations.

PMID- 22160034
TI  - Posttransplantation maintenance therapy and optimal frontline therapy in myeloma.
AB  - One of the major efforts to improve the results of intensive therapy and
      autologous stem cell transplantation (ASCT) in multiple myeloma involves the
      integration of novel agents into the transplantation sequence. This can include
      their administration before, during, and after the transplantation procedure.
      Several phase 2 and 3 studies have evaluated the use of novel agents as part of
      induction therapy before transplantation to produce higher response rates and
      progression-free survival (PFS). Similarly, posttransplantation maintenance-or
      consolidation-with these agents consistently improves PFS. Survival benefits have
      been more difficult to demonstrate, although one trial using bortezomib before
      and after transplantation and a second using lenalidomide as maintenance have
      shown significantly longer survival times. This article reviews the different
      regimens used with ASCT, with an emphasis on randomized trials.

PMID- 22160035
TI  - What is the benefit of maintenance therapy with lenalidomide or bortezomib after
      autologous stem cell transplantation in multiple myeloma and what is the risk of
      developing a secondary primary malignancy?
AB  - An otherwise healthy 60-year-old male was diagnosed with stage II multiple
      myeloma by the International Staging System characterized by anemia, diffuse
      lytic bone lesions, IgG kappa paraproteinemia, 45% bone marrow plasmacytosis and
      the t(4;14) by FISH and conventional cytogenetics. The patient had a very good
      partial remission with initial induction therapy consisting of four 3-week cycles
      of bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, and 11 plus dexamethasone 40 mg
      days 1-4 (all cycles), followed by a cyclophosphamide and G-CSF mobilized
      melphalan 200 mg/m(2) autologous stem cell transplantation (ASCT) and experienced
      minimal side effects. He is doing well 60 days post-ASCT and is in a near
      complete remission. His oncologist recommends maintenance therapy with
      lenalidomide or bortezomib, but the patient is concerned about the increased risk
      of developing a secondary malignancy (SM), and because he has had such an
      encouraging response to induction therapy, he wonders if he could remain off
      therapy.

PMID- 22160036
TI  - Genetic and epigenetic complexity in myeloproliferative neoplasms.
AB  - The past 7 years have witnessed remarkable progress in our understanding of the
      genetics of BCR-ABL-negative myeloproliferative neoplasms (MPNs) and has revealed
      layers of unexpected complexity. Deregulation of JAK2 signaling has emerged as a
      central feature, but despite having biological activities that recapitulate the
      cardinal features MPNs in model systems, JAK2 mutations are often secondary
      events. Several other mutated genes have been identified with a common theme of
      involvement in the epigenetic control of gene expression. Remarkably, the somatic
      mutations identified to date do not seem to be acquired in any preferred order,
      and it is possible that the disease-initiating events remain to be identified.
      The finding of complex clonal hierarchies in many cases suggests genetic
      instability that, in principle, may be inherited or acquired. A common haplotype
      has been identified that is strongly associated with the acquisition of JAK2
      mutations, but the cause of relatively high-penetrance familial predisposition to
      MPNs remains elusive. This review summarizes the established facts relating to
      the genetics of MPNs, but highlights recent findings and areas of controversy.

PMID- 22160037
TI  - Management of essential thrombocythemia.
AB  - Essential thrombocythemia (ET) is a Philadelphia chromosome (Ph)-negative
      myeloproliferative neoplasm (MPN) characterized by thrombocytosis and
      megakaryocytic hyperplasia of the bone marrow, with presence of the JAK2 V617F
      mutation in 50%-60% of patients. ET evolves to myelofibrosis in a minority of
      cases, whereas transformation to acute leukemia is rare and increases in
      association with the use of certain therapies. Survival of ET patients does not
      substantially differ from that of the general population. However, important
      morbidity is derived from vascular complications, including thrombosis,
      microvascular disturbances, and bleeding. Because of this, treatment of ET must
      be aimed at preventing thrombosis and bleeding without increasing the risk of
      transformation of the disease. Patients are considered at high risk of thrombosis
      if they are older than 60 years or have a previous history of thrombosis and at
      high risk of bleeding if platelet counts are > 1500 * 10(9)/L. Patients with low
      risk ET are usually managed with low-dose aspirin, whereas treatment of high-risk
      ET is based on the use of cytoreductive therapy, with hydroxyurea as the drug of
      choice and IFN-alpha being reserved for young patients or pregnant women. For
      patients resistant or intolerant to hydroxyurea, anagrelide is recommended as
      second-line therapy. Strict control of coexistent cardiovascular risk factors is
      mandatory for all patients. The role in ET therapy of new drugs such as pegylated
      IFN or the JAK2 inhibitors is currently under investigation.

PMID- 22160038
TI  - Management of myelofibrosis.
AB  - Myelofibrosis (MF), either primary or arising from previous polycythemia vera
      (PV) or essential thrombocythemia (ET), is the worst among the chronic
      myeloproliferative neoplasms in terms of survival and quality of life. Patients
      with MF have to face several clinical issues that, because of the poor
      effectiveness of medical therapy, surgery or radiotherapy, represent largely
      unmet clinical needs. Powerful risk stratification systems, applicable either at
      diagnosis using the International Prognostic Scoring System (IPSS) or during the
      variable course of illness using the Dynamic International Prognostic Scoring
      System (DIPSS) and DIPSS Plus, allow recognition of categories of patients with
      survival times ranging from decades to < 2 years. These scores are especially
      important for therapeutic decisions that include allogeneic stem cell
      transplantation (allogeneic SCT), the only curative approach that still carries a
      nonnegligible risk of morbidity and mortality even with newest reduced intensity
      conditioning (RIC) regimens. Discovery of JAK2V617F mutation prompted the
      development of clinical trials using JAK2 inhibitors; these agents overall have
      resulted in meaningful symptomatic improvement and reduction of splenomegaly that
      were otherwise not achievable with conventional therapy. Intriguing differences
      in the efficacy and tolerability of JAK2 inhibitors are being recognized, which
      could lead to a nonoverlapping spectrum of activity/safety. Other agents that do
      not directly target JAK2 and have shown symptomatic efficacy in MF are
      represented by inhibitors of the mammalian target of rapamycin (mTOR) and histone
      deacetylases (HDACs). Pomalidomide appears to be particularly active against MF
      associated anemia. However, because these agents are all poorly effective in
      reducing the burden of mutated cells, further advancements are needed to move
      from enhancing our ability to palliate the disease to arriving at an actual cure
      for MF.

PMID- 22160039
TI  - Current treatment of Philadelphia chromosome-positive acute lymphoblastic
      leukemia.
AB  - The author discusses both the standards of care and more controversial areas in
      the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

PMID- 22160040
TI  - Late effects of acute lymphoblastic leukemia therapy in patients diagnosed at 0
      20 years of age.
AB  - Survival rates for children with acute lymphoblastic leukemia (ALL) have
      increased dramatically over the past 4 decades, with 5-year survival rates of >
      90% in recent trials. With the increasing number of children and adolescents
      cured of ALL, identifying and characterizing the occurrence of long-term adverse
      late effects has become increasingly important. In this young population,
      successful treatment of ALL is associated with increased risk of adverse outcomes
      such as late mortality, second neoplasms, chronic health conditions, endocrine
      dysfunction, and psychological function. Research efforts conducted through large
      survivor cohorts, such as the Childhood Cancer Survivor Study, are providing new
      and important insights into the very long-term consequences of ALL therapy, while
      providing direction for screening recommendations and intervention-based
      approaches for reducing late morbidity and mortality.

PMID- 22160041
TI  - Novel antibody-based therapies for acute lymphoblastic leukemia.
AB  - A major breakthrough in the treatment of acute lymphoblastic leukemia (ALL) was
      the availability of targeted therapies targeting either specific transcripts,
      such as bcr-abl fusion protein by tyrosine kinase inhibitors (TKIs), or specific
      antigens by mAbs. ALL blast cells express a variety of specific antigens (eg,
      CD19, CD20, CD22, CD33, and CD52) that serve as targets for mAbs. To date, the
      most data are available for anti-CD20 (rituximab), which has been combined with
      chemotherapy for the treatment of mature B-ALL/Burkitt lymphoma. Studies with
      rituximab have also been completed in B-precursor ALL. Another antigen, CD19, is
      of great interest due to a very high rate of expression in ALL. It can be
      targeted by a bispecific mAb, blinatumomab, directed against CD19 and CD3.
      Smaller studies or case reports are also available for the anti-CD52
      (alemtuzumab), anti-CD22 (epratuzumab), and anti-CD33 (gemtuzumab) mAbs.
      Available data demonstrate that mAb therapy in ALL is a highly promising
      treatment approach. However, several details for an optimal treatment approach,
      such as the required level of antigen expression, timing, schedule, dosage, and
      stage of disease, still need to be defined.

PMID- 22160042
TI  - World health organization classification, evaluation, and genetics of the
      myeloproliferative neoplasm variants.
AB  - There is no single category in the fourth edition (2008) of the World Health
      Organization (WHO) classification of myeloid neoplasms that encompasses all of
      the diseases referred to by some authors as the myeloproliferative neoplasm (MPN)
      "variants." Instead, they are considered as distinct entities and are distributed
      among various subgroups of myeloid neoplasms in the classification scheme. These
      relatively uncommon neoplasms do not meet the criteria for any so-called
      "classical" MPN (chronic myelogenous leukemia, polycythemia vera, primary
      myelofibrosis, or essential thrombocythemia) and, although some exhibit
      myelodysplasia, none meets the criteria for any myelodysplastic syndrome (MDS).
      They are a diverse group of neoplasms ranging from fairly well-characterized
      disorders such as chronic myelomonocytic leukemia to rare and thus poorly
      characterized disorders such as chronic neutrophilic leukemia. Recently, however,
      there has been a surge of information regarding the genetic infrastructure of
      neoplastic cells in the MPN variants, allowing some to be molecularly defined.
      Nevertheless, in most cases, correlation of clinical, genetic, and morphologic
      findings is required for diagnosis and classification. The fourth edition of the
      WHO classification provides a framework to incorporate those neoplasms in which a
      genetic abnormality is a major defining criterion of the disease, such as those
      associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1, as
      well as for those in which no specific genetic defect has yet been discovered and
      which remain clinically and pathologically defined. An understanding of the
      clinical, morphologic, and genetic features of the MPN variants will facilitate
      their diagnosis.

PMID- 22160044
TI  - Myelodysplastic/myeloproliferative neoplasms.
AB  - According to the World Health Organization (WHO) classification of tumors of
      hematopoietic and lymphoid tissues, myelodysplastic/myeloproliferative neoplasms
      are clonal myeloid neoplasms that have some clinical, laboratory, or morphologic
      findings that support a diagnosis of myelodysplastic syndrome, and other findings
      that are more consistent with myeloproliferative neoplasms. These disorders
      include chronic myelomonocytic leukemia, atypical chronic myeloid leukemia (BCR
      ABL1 negative), juvenile myelomonocytic leukemia, and
      myelodysplastic/myeloproliferative neoplasms, unclassifiable. The best
      characterized of these latter unclassifiable conditions is the provisional entity
      defined as refractory anemia with ring sideroblasts associated with marked
      thrombocytosis. This article focuses on myelodysplastic/myeloproliferative
      neoplasms of adulthood, with particular emphasis on chronic myelomonocytic
      leukemia and refractory anemia with ring sideroblasts associated with marked
      thrombocytosis. Recent studies have partly clarified the molecular basis of these
      disorders, laying the groundwork for the development of molecular diagnostic and
      prognostic tools. It is hoped that these advances will soon translate into
      improved therapeutic approaches.

PMID- 22160045
TI  - Hematopoietic stem cell transplantation for sickle cell disease: current practice
      and emerging trends.
AB  - Allogeneic HSCT controls sickle cell disease (SCD)-related organ damage and is
      currently the only curative therapy available. Over the last 2 decades, HSCT has
      been limited largely to myeloablative matched sibling donor (MSD) procedures that
      are feasible only in a minority of patients. As the natural history of the
      disease has evolved, it is clear that subsets of patients with severe disease are
      at risk for sudden death, devastating CNS and pulmonary complications, and
      debilitating vasoocclusive crises. For these patients, the benefits of
      transplantation can outweigh the risks if HSCT can be safely and successfully
      performed with low early and late toxicities. This review describes advances and
      ongoing investigation of HSCT for SCD from the perspectives of recipient age and
      presentation, donor stem cell source, intensity of conditioning, family and
      medical perspectives, and other variables that influence outcome. Ultimately,
      HSCT should be viewed as a viable treatment option for SCD on par with other
      therapies for select patients who can benefit from the procedure.

PMID- 22160043
TI  - Eosinophilic myeloproliferative disorders.
AB  - Despite recent attempts to define and classify patients with marked eosinophilia
      and features consistent with myeloproliferative disease, areas of controversy
      remain. These are particularly apparent in situations in which multiple lineages
      are involved in a clonal process and clinical manifestations are overlapping.
      Although the introduction of new molecular diagnostics and targeted therapies has
      begun to clarify the boundaries between some of these disorders, several
      questions remain with respect to the classification of patients with
      myeloproliferative hypereosinophilic syndrome (HES) of unknown etiology.

PMID- 22160046
TI  - Successes and failures of stem cell transplantation in autoimmune diseases.
AB  - Over the past 15 years, more than 1500 patients have received HSCT, mostly
      autologous, as treatment for a severe autoimmune disease (AD). More than 1000 of
      these have been registered in the European Group for Bone Marrow Transplantation
      (EBMT) and European League Against Rheumatism (EULAR) combined database. A recent
      retrospective analysis of 900 patients showed that the majority had multiple
      sclerosis (MS; n = 345) followed by systemic sclerosis (SSc; n = 175), systemic
      lupus erythematosus (SLE; n = 85), rheumatoid arthritis (RA; n = 89), juvenile
      idiopathic arthritis (JIA; n = 65), and idiopathic cytopenic purpura (ITP; n =
      37). An overall 85% 5-year survival and 43% progression-free survival was seen,
      with 100-day transplantation-related mortality (TRM) ranging between 1% (RA) and
      11% (SLE and JIA). Approximately 30% of patients in all disease subgroups had a
      complete response, often durable despite full immune reconstitution. In many
      patients, such as in those with SSc, morphological improvement such as reduction
      of skin collagen and normalization of microvasculature was documented beyond any
      predicted known effects of intense immunosuppression alone. The high TRM was in
      part related to conditioning intensity, comorbidity, and age, but until the
      results of the 3 prospective randomized trials are known, an evidence-based
      modification of the conditioning regimen will not be possible.(1) In recent
      years, multipotent mesenchymal stromal cells (MSCs) have been tested in various
      AD, exploiting their immune-modulating properties and apparent low acute
      toxicity. Despite encouraging small phase 1/2 studies, no positive data from
      randomized, prospective studies are as yet available in the peer-reviewed
      literature.

PMID- 22160047
TI  - Stem cell transplantation in inherited metabolic disorders.
AB  - Allogeneic HSCT is performed for a small number of inborn errors of metabolism
      (IEM). Over the last years, transplantation outcomes have improved in this group
      of patients as the factors that predicted for poor transplantation outcomes were
      understood and addressed. The role of transplantation and its potential benefit
      for an individual patient with a certain IEM is therefore now much better
      defined. In parallel with improvements in transplantation techniques, other
      therapies such as pharmacological enzyme replacement therapy (ERT), substrate
      inhibition, and gene therapy have been developed and are increasingly available
      to clinicians and their patients. This review covers the following areas: (1) the
      scientific principles that underpin transplantation in IEM; (2) the variables of
      the transplantation process itself that predict for successful outcome in terms
      of engrafted survival after HSCT; (3) the reasons that some apparently
      phenotypically similar disorders might respond very differently to
      transplantation therapy; (4) the factors that currently influence the response of
      a particular patient with a particular disease to allogeneic transplantation, and
      how these factors might be manipulated in the future to further improve
      transplantation outcomes in different metabolic illnesses; and (5) how other
      therapeutic modalities, including ERT, gene therapy, and substrate reduction
      therapy, might complement and compete with HSCT in the coming years.

PMID- 22160048
TI  - Allogeneic immunotherapy to optimize the graft-versus-tumor effect: concepts and
      controversies.
AB  - Allogeneic stem cell transplantation (SCT) can be considered the most successful
      method of adoptive immunotherapy of cancer. It is successful in part because of
      the potent graft-versus-tumor (GVT) effects of the donor graft, which are
      independent of the conditioning regimen. This potent GVT reaction can be
      harnessed in some cases to treat patients who relapse after allogeneic SCT with
      the use of donor leukocyte infusions (DLIs). This has led to the rapid
      development of reduced-intensity conditioning (RIC) regimens for allogeneic SCT,
      an approach that relies primarily on GVT activity. However, the effects of GVT
      have clear disease specificity and remain associated with significant GVHD.
      Optimization of GVT induction will require a better understanding of the
      important target antigens and effector cells, as well as the development of
      methods that enhance GVT reactivity without excessive GVHD. The appropriate
      clinical setting and timing for GVT induction need to be defined more clearly,
      but ultimately, the immunologic control of cancer through allogeneic adoptive
      immunotherapy represents one of the most potent and promising therapeutic
      strategies for patients with hematologic malignancies.

PMID- 22160049
TI  - Posttransplantation vaccination: concepts today and on the horizon.
AB  - Allogeneic hematopoietic stem cell transplantation (allogeneic HSCT) remains a
      curative treatment for hematological malignancies resistant to other treatment
      approaches through the unique GVL effect. However, relapse remains a major cause
      of treatment failure after allogeneic HSCT for patients with high-risk
      hematological malignancies. Further improvements in exploiting the GVL effect to
      prevent relapse in high-risk leukemias while minimizing toxicity have focused on
      the use of targeted antileukemic immunotherapy. These strategies include methods
      to boost the GVL effect with leukemia vaccines or the adoptive transfer of
      leukemia-specific lymphocytes. Vaccines can be classified as those against
      defined antigens such as minor histocompatibility antigens (mHags) or leukemia
      associated antigens (PR1, WT1, and BCR-ABL) and those that have broad
      "antileukemic" activity such as engineered irradiated leukemia cells or leukemia
      derived dendritic cells (DCs). The unique posttransplantation milieu, which is
      characterized by lymphopenia, regulatory T-cell depletion, and the release of
      growth factors, provides a unique opportunity for effective antitumor
      immunotherapy and augmenting specific GVL responses. This review focuses on
      approaches to enhancimg the GVL response by combining allogeneic HSCT with
      vaccination.

PMID- 22160050
TI  - Complications, diagnosis, management, and prevention of CMV infections: current
      and future.
AB  - Although major progress has been made in the prevention of CMV disease after
      hematopoietic cell transplantation (HCT), specific problems remain and available
      antiviral agents are associated with major toxicities. This article reviews
      current aspects of CMV diagnosis, prevention, and treatment in HCT recipients and
      defines areas of unmet medical need.

PMID- 22160051
TI  - Optimal therapy of advanced Hodgkin lymphoma.
AB  - Advanced-stage Hodgkin lymphoma (HL) has become a curable disease in the majority
      of patients. Research during the last decade has challenged chemotherapy with
      Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) as the standard of care
      and debates continue regarding the role of radiation therapy (RT) in this patient
      population. The incorporation of interim positron emission tomography (PET)
      imaging and, recently, further characterization of HL on cellular and molecular
      levels are emerging as tools for treatment stratification and predictors of
      disease status. Newer targeted therapies have emerged that are very effective in
      the relapsed setting and are actively being explored as frontline therapy.
      Lastly, the expanding population of survivors cured of HL outnumbers patients
      with the disease and needs to be monitored for therapy-related late effects.

PMID- 22160052
TI  - Positron emission tomography in the management of Hodgkin lymphoma.
AB  - Accurate imaging of lymphoma is essential for optimal management. Positron
      emission tomography (PET), by providing both anatomic and functional information,
      is fundamentally altering staging, monitoring of response, response assessment,
      and choice of treatment modality for lymphomas, including Hodgkin lymphoma. This
      imaging technique, when used carefully in conjunction with standard testing,
      increases the sensitivity of lesion detection, provides an opportunity to monitor
      the quality of response during treatment, permits separation of fibronecrotic
      scar tissue from viable tumor, and adds prognostic information. PET has become
      integral to modern lymphoma management, but as a relatively new diagnostic
      technique, it is still being studied and neither its full potential nor its major
      limitations are fully understood. Discussed herein are recent observations from
      clinical trials and single-center experiences with PET to explore its advantages
      and limitations from a clinician's point of view.

PMID- 22160053
TI  - Late effects in the era of modern therapy for Hodgkin lymphoma.
AB  - Extended-field and subtotal nodal radiation therapy (RT), developed in the 1960s,
      was the first reliably curative treatment for early-stage Hodgkin lymphoma (HL).
      However, the large volume of normal tissue irradiated resulted in significant
      delayed toxicity, including cardiac disease and second cancers (SCs). The 30-year
      cumulative incidence of heart disease among adult survivors receiving 40-45 Gy of
      extended-field or mantle RT is approximately 30%; the incidence of SCs is
      similar. Improving disease control while reducing the toxicity of treatment has
      been a major objective of HL trials for more than 2 decades. Contemporary
      involved-field RT (IFRT) reduces irradiated volumes and produces significant
      reductions in normal tissue dose compared with historic treatments. Recent data
      indicate that, compared with mantle RT, IFRT reduces the relative risk of breast
      cancer among young females receiving mediastinal RT by approximately 60% and also
      reduces cardiac dose. The recent transition to involved-node RT allows further
      reductions in normal tissue dose. Response-adapted therapy is being evaluated in
      clinical trials as a means of identifying those patients most likely to benefit
      from treatment reduction or intensification, enhanced screening will facilitate
      early intervention to reduce the clinical burden of late effects, and there is
      increasing interest in elucidating the genetic correlates of treatment toxicity.

PMID- 22160054
TI  - B cells behaving badly: a better basis to behold belligerence in B-cell
      lymphomas.
AB  - A plethora of genetic abnormalities has been described in B-cell lymphomas, some
      of which arise when physiologic mechanisms involved in the generation of
      immunologic diversity go awry. Several different lymphoma types, such as
      follicular lymphoma (FL), mantle cell lymphoma (MCL), and Burkitt lymphoma (BL),
      are associated with hallmark translocations that occur as a consequence of these
      errors (t(14;18)(q32;q21), t(11;14)(q13;q32), and t(8;14)(q24;q32),
      respectively); however, none of these associations is absolute and none is
      completely diagnostically specific or sensitive. The advantages and limitations
      of a variety of different testing strategies in the 2 most common lymphomas, FL
      and diffuse large B-cell lymphoma (DLBCL), are reviewed herein, including an
      evaluation of the role of PCR-based approaches, FISH, and more nascent genomic
      technologies. The use of immunophenotypic strategies that may potentially
      provide, albeit imperfectly, more user-friendly surrogates for underlying genetic
      aberrations and cell-of-origin designations derived from gene-expression
      profiling analyses are also discussed. Finally, a newly designated category of
      lymphoma with features intermediate between DLBCL and BL is appraised,
      highlighting the central role of genetic analysis in this diagnostic gray zone.

PMID- 22160055
TI  - Tricky and terrible T-cell tumors: these are thrilling times for testing:
      molecular pathology of peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) encompass a group of rare and usually
      clinically aggressive diseases. The classification and diagnosis of these
      diseases are compounded by their marked pathological heterogeneity and complex
      clinical features. With the exception of ALK-positive anaplastic large cell
      lymphoma (ALCL), which is defined on the basis of ALK rearrangements, genetic
      features play little role in the definition of other disease entities. In recent
      years, hitherto unrecognized chromosomal translocations have been reported in
      small subsets of PTCLs, and genome-wide array-based profiling investigations have
      provided novel insights into their molecular characteristics. This article
      summarizes the current knowledge on the best-characterized genetic and molecular
      alterations underlying the pathogenesis of PTCLs, with a focus on recent
      discoveries, their relevance to disease classification, and their management
      implications from a diagnostical and therapeutical perspective.

PMID- 22160057
TI  - Targeting epigenetic programs in MLL-rearranged leukemias.
AB  - Rearrangements of the Mixed-Lineage Leukemia (MLL) gene are found in > 70% of
      infant leukemia, ~ 10% of adult acute myelogenous leukemia (AML), and many cases
      of secondary acute leukemias. The presence of an MLL rearrangement generally
      confers a poor prognosis. There are more than 60 known fusion partners of MLL
      having some correlation with disease phenotype and prognosis. The most common
      fusion proteins induce the inappropriate expression of homeotic (Hox) genes,
      which, during normal hematopoiesis, are maintained by wild-type MLL. MLL
      rearranged leukemias display remarkable genomic stability, with very few gains or
      losses of chromosomal regions. This may be explained by recent studies suggesting
      that MLL-rearranged leukemias are largely driven by epigenetic dysregulation.
      Several epigenetic regulators that modify DNA or histones have been implicated in
      MLL-fusion driven leukemogenesis, including DNA methylation, histone acetylation,
      and histone methylation. The histone methyltransferase DOT1L has emerged as an
      important mediator of MLL-fusion-mediated leukemic transformation. The clinical
      development of targeted inhibitors of these epigenetic regulators may therefore
      hold promise for the treatment of MLL-rearranged leukemia.

PMID- 22160056
TI  - Many multiple myelomas: making more of the molecular mayhem.
AB  - Multiple myeloma (MM) is malignancy of isotype-switched, BM-localized plasma
      cells that frequently results in bone destruction, BM failure, and death.
      Important molecular subgroups are identified by three classes of recurrent
      immunoglobulin gene translocations and hyperdiploidy, both of which affect
      disease course. From a clinical standpoint, it is critical to identify MM
      patients carrying the t(4;14) translocation, which is present in 15% of myelomas
      and is associated with dysregulation of WHSC1/MMSET and often FGFR3. These
      patients should all receive bortezomib as part of their initial induction
      treatment because this has been shown to significantly prolong survival. In
      contrast, patients with translocations affecting the MAF family of transcription
      factors, del17p, or gene-expression profiling (GEP)-defined high-risk disease
      appear to have a worse prognosis that is not dramatically improved by any
      intervention. These patients should be enrolled in innovative clinical trials.
      The remaining patients with cyclin D translocations or hyperdiploidy do well with
      most therapies, and the goal should be to control disease while minimizing
      toxicity.

PMID- 22160058
TI  - Tyrosine kinase inhibitor use in pediatric Philadelphia chromosome-positive acute
      lymphoblastic anemia.
AB  - Until recently, pediatric Philadelphia chromosome-positive (Ph(+)) acute
      lymphoblastic leukemia (ALL) was associated with an extremely poor outcome when
      treated with chemotherapy alone, and only modest survival benefits were obtained
      with the widespread use of hematopoietic stem cell transplantation (HSCT). The
      development of first-generation (imatinib) and second-generation (dasatinib and
      nilotinib) tyrosine kinase inhibitors (TKIs) that target the BCR-ABL1 fusion
      protein produced by the Ph chromosome revolutionized the treatment of chronic
      myelogenous leukemia (CML). The Children's Oncology Group (COG) AALL0031 trial
      showed that the addition of imatinib to intensive chemotherapy did not cause
      increased toxicity and resulted in 3-year event-free survival rates that were
      more than double those of historical control data from the pre-imatinib era.
      These findings create a new paradigm for integrating molecularly targeted agents
      with conventional chemotherapy and call for a reassessment of the routine use of
      HSCT for children and adolescents with Ph(+) ALL. Second-generation TKIs have
      theoretical advantages over imatinib, and are now being tested in Ph(+) ALL. The
      focus of contemporary trials is to define the optimal use of chemotherapy, HSCT,
      and TKI in Ph(+) ALL. In the coming years, it is anticipated that additional
      agents will become available to potentiate TKI therapy and/or circumvent TKI
      resistance in Ph(+) ALL. Recent genomic studies have identified a subtype of high
      risk pediatric B-cell-precursor ALL with a gene-expression profile similar to
      that of Ph(+) ALL, suggestive of active kinase signaling. Many of these Ph-like
      ALL cases harbor chromosome rearrangements and mutations that dysregulate
      cytokine receptor and kinase signaling, and these leukemias may also be
      candidates for TKI therapy.

PMID- 22160059
TI  - Pediatric acute leukemia therapies informed by molecular analysis of high-risk
      disease.
AB  - The acute leukemias are the most common cancer of children, adolescents, and
      young adults. These diseases are characterized by a tremendous variability in
      clinical course, prompting a continuing search for accurate predictors of
      outcome. Using algorithms based on clinical features at presentation, response to
      therapy, and several molecular analyses, some patients are diagnosed with
      features of high-risk disease and comparatively greater risk for relapse.
      Molecular analyses of patients with high-risk acute leukemias have resulted in an
      improved understanding of how dysregulated cellular signaling can affect
      resistance to conventional therapy. Whereas exciting discoveries continue to be
      made in the identification of relevant molecular biomarkers and targeted
      therapies, the challenges and opportunities associated with these findings remain
      to be clearly defined in future clinical trials.

PMID- 22160060
TI  - Recommendations for broader coverage antifungal prophylaxis in childhood acute
      myeloid leukemia: ASH evidence-based review 2011.
AB  - A 16-year-old female diagnosed with acute myeloid leukemia (AML) with inversion
      16, a favorable prognostic indicator, has persistent neutropenia after her fourth
      cycle of dose-intensified chemotherapy. She was recently admitted for treatment
      with empiric antibiotics for febrile neutropenia, and an astute intern noticed a
      new lesion on her right foot with a dark necrotic center. A biopsy of the lesion
      showed spreading hyphae, consistent with Aspergillus. Despite her compliance with
      fluconazole fungal prophylaxis, computed tomography imaging revealed disseminated
      aspergillosis involving her lungs, liver, and kidneys. Amphotericin was started,
      but systemic fungemia and the development of multiorgan failure resulted in her
      death. You are in the difficult position of having to explain to her parents that
      she died in remission from chemotherapy-related complications. All of those
      involved in this unfortunate scenario wonder if something could have been done to
      prevent her death.

PMID- 22160061
TI  - What to do when you suspect an inherited platelet disorder.
AB  - Inherited platelet disorders (IPDs) comprise a heterogenous group of diseases
      that include defects in platelet function and disordered megakaryopoiesis. Some
      IPDs overlap as both defects in function and thrombopoiesis, resulting in both
      altered aggregation and/or secretion and thrombocytopenia. This review examines
      the key features of the presentation of IPDs in children and adults and presents
      a diagnostic algorithm for the evaluation of these patients. In addition, recent
      advances in our understanding of the pathophysiology of platelet disorders are
      addressed, with attention given to some of the novel genetic associations.
      Finally, treatment options and future therapies are briefly discussed.

PMID- 22160062
TI  - Diagnosis and management of immune thrombocytopenia in the era of thrombopoietin
      mimetics.
AB  - The recognition of that patients with Immune Thrombocytopenia (ITP) have
      functional thrombopoietin deficiency and decreased platelet production due to
      immune-mediated megakaryocytic injury has challenged the traditional view of this
      disease as predominantly a disorder of antibody-mediated platelet destruction.
      The therapy of chronic refractory ITP has been transformed by the approval of the
      thrombopoietin minetics, romiplostim and eltrombopag, which have shown remarkable
      efficacy in randomized trials. The use of these agents earlier in the disease
      course after failure of corticosteroid therapy remains controversial. In this
      article, we review the current data on the efficacy and safety of thrombopoietin
      receptor agonists and discuss other therapies as well as diagnostic work up of
      ITP.

PMID- 22160063
TI  - Acquired disorders of platelet function.
AB  - Platelet dysfunction is commonly acquired due to medications, procedures, medical
      conditions, and underlying hematologic disease. These issues are presented, the
      data reviewed, and recommendations given herein. Many medications and dietary
      supplements have platelet-inhibitory effects in vitro, although the clinical
      effects on bleeding risks are unclear for many. Platelet-inhibitory drugs are key
      in the treatment of vascular disease. Data are available to aid in the management
      of these medications to prevent hemorrhagic complications. Bleeding in patients
      with renal failure has decreased with improved dialysis and the use of
      erythropoietin, but remains a challenge. Platelet dysfunction accompanies cardiac
      valvular disease and use of cardiopulmonary bypass (CPB) and extracorporeal
      membrane oxygenation. Hematologic disorders including myeloproliferative
      disorders (MPDs), myelodysplasia, paraproteinemias, and immune thrombocytopenia
      (ITP) can also be associated with hemorrhagic complications due to platelet
      dysfunction. Knowledge of which factors affect bleeding risk and how to treat
      individuals with acquired platelet dysfunction are important in optimizing
      patient care.

PMID- 22160064
TI  - Biological rationale for new drugs in the bleeding disorders pipeline.
AB  - Since the introduction of replacement coagulation factor infusions for the
      treatment of hemophilia in the 1970s and subsequent improvements in the safety
      profile of available factor VIII (FVIII) and factor IX (FIX) concentrates,
      mortality among patients with hemophilia has improved considerably and now
      parallels that of the noncoagulopathic population in developed countries.
      Substantial morbidity, however, continues from the development of inhibitory
      antibodies, a recognized complication of clotting factor replacement; from
      infections and thrombosis complicating placement of central venous catheters,
      which are required in children with hemophilia due to frequent prophylactic
      infusions of coagulation factors with defined half-lives; and from disabling
      joint disease in individuals without access to costly prophylaxis regimens. In
      response to the need for long-acting, more potent, less immunogenic, and more
      easily administered therapies, an impressive array of novel agents is nearly
      ready for use in the clinical setting. These therapeutics derive from rational
      bioengineering of recombinant coagulation factors or from the discovery of
      nonpeptide molecules that have the potential to support hemostasis through
      alternative pathways. The number of novel agents in clinical trials is
      increasing, and many of the initial results are promising. In addition to
      advancing treatment of bleeding episodes or enabling adherence to prophylactic
      infusions of clotting factor concentrate, newer therapeutics may also lead to
      improvements in joint health, quality of life, and tolerability of iatrogenic or
      comorbidity-associated bleeding challenges.

PMID- 22160065
TI  - What is the evidence for the use of immunomodulatory agents to eradicate
      inhibitory antibodies in patients with severe hemophilia a who have previously
      failed to respond to immune tolerance induction?
AB  - An 18-year-old man has severe hemophilia A that has been complicated by a high
      titer inhibitory antibody (peak 170 BU/mL). He had previously failed a trial of
      immune tolerance induction (ITI) using daily high-dose (100 units/kg/d) factor
      VIII (FVIII) for 20 months and would like to know if immunomodulatory agents,
      with or without another course of ITI, might eradicate the inhibitor.

PMID- 22160066
TI  - Current controversies in the formation and treatment of alloantibodies to factor
      VIII in congenital hemophilia A.
AB  - Hemophilia A is a rare bleeding disorder treated with numerous factor VIII
      (FVIII)-containing replacement concentrates. This treatment approach has led to
      the formation of alloantibodies that neutralize the FVIII activity (inhibitors)
      conveyed by these commercially available concentrates in ~ 25% of patients with
      severe hemophilia A (FVIII activity < 1% of normal). This phenomenon
      significantly complicates the treatment of these patients and compromises the
      effectiveness and efficiency of these products to reverse or prevent bleeding
      complications. Studying the population with alloantibody inhibitors is imperative
      but difficult due to the overall small number of individuals affected and the
      heterogeneity within this limited group. Furthermore, few randomized clinical
      trials have been conducted to answer pertinent questions so many controversies
      persist. This article focuses on the conflicting data on the variables associated
      with alloantibody FVIII inhibitor development with a particular emphasis on age
      and intensity of first treatment, the role of primary prophylaxis regimens in
      modulating this phenomenon, and the degree of purity of FVIII product as a
      potential contributing risk factor. The optimal dosing regimen and type of FVIII
      replacement product that should be used to achieve the highest success rate in
      immune tolerance induction (ITI) protocols are also discussed, as well as whether
      the addition of immunomodulatory agents, especially rituximab, to ITI regimens
      enhances the durability of ITI and the eradication of alloantibody FVIII
      inhibitors.

PMID- 22160067
TI  - Costs of care in hemophilia and possible implications of health care reform.
AB  - Economic evaluation in health care is increasingly used to assist policy makers
      in their difficult task of allocating limited resources. The high cost of care,
      including that for clotting factor concentrates, makes hemophilia a potential
      target for cost-cutting efforts by health care payers. Although the appropriate
      management of hemophilia is key to minimizing and preventing long-term morbidity,
      comparative effectiveness studies regarding the relative benefit of different
      treatment options are lacking. Cost-of-illness (COI) analysis, which includes
      direct and indirect costs from a societal perspective, can provide information to
      be used in cost-effectiveness and other economic analyses. Quality-of-life
      assessment provides another methodology with which to measure outcomes and
      benefits of appropriate disease management. Health care reform has implications
      for individuals with hemophilia and their families through changes in payment,
      insurance coverage expansion, and health care delivery system changes that reward
      quality and stimulate cooperative, team-based care. Providers will benefit from
      the expansion of insurance coverage and some financial benefits in rural areas,
      and from the expansion of coverage for preventive services. Accountable care
      organizations will potentially change the way providers are paid and financial
      incentives under reform will reward high quality of care.

PMID- 22160068
TI  - Pulmonary hypertension, tricuspid regurgitant velocity screening, and the nitric
      oxide pathway.
AB  - Chronic pulmonary complications, including pulmonary hypertension (PH), are
      common in sickle cell disease (SCD), especially in adults with sickle cell anemia
      (SCA). The underlying pathophysiology is complex and variable, involving multiple
      biological systems. Recent emphasis has been placed on the pleotropic biological
      factor nitric oxide (NO). An elevated tricuspid regurgitant velocity (TRV)
      appears to have limitations in specificity in SCA, but may indicate the presence
      of PH, a diagnosis confirmed by right heart catheterization. TRV has been used in
      recent clinical trials to identify or define subjects with PH for enrollment into
      PH-specific interventions; these include sildenafil, which enhances NO-induced
      vasorelaxation. Results from a controlled trial show no benefit and an unexpected
      increase in adverse events, emphasizing the biological complexities of SCA.
      Management remains principally supportive, includes recognition and treatment of
      comorbidities, and may incorporate individualized PH-specific strategies (despite
      recent trials) based on appropriate diagnostic testing. Ultimately, therapy is
      likely to be multimodal and tailored to the processes identified to be the most
      contributory in a given individual. Based on the relative prevalence of the
      conditions, routine screening for asthma in children with SCD and by Doppler
      echocardiography to measure TRV as an initial screen for PH in adults with SCA
      may be warranted. Data are limited regarding the clinical utility of screening in
      other forms of SCD and the pediatric population. This article offers an
      individual perspective on practical and challenging clinical considerations.

PMID- 22160069
TI  - Secondary prevention of overt strokes in sickle cell disease: therapeutic
      strategies and efficacy.
AB  - Overt strokes, previously one of the most common neurological complications in
      sickle cell disease (SCD), have become far less frequent with routine
      transcranial Doppler (TCD) assessment followed by regular blood transfusion
      therapy. Nevertheless, children and adults with SCD continue to have overt
      strokes, and in the foreseeable future will continue to require secondary
      prevention of strokes. With the exception of the most recently completed "Stroke
      With Transfusions Changing to Hydroxyurea" Trial (SWiTCH; NCT00122980),
      randomized trials providing best evidence for long-term management of overt
      strokes in SCD is lacking. Instead of randomized clinical trials, a series of
      observational and single-arm studies have predominated. This review assesses the
      best available evidence for acute and chronic management of overt stroke and the
      efficacy of regular blood transfusion therapy, hydroxyurea therapy, and
      hematopoietic stem cell transplantation (HSCT), including matched sibling donor
      and unrelated HSCT.

PMID- 22160070
TI  - Primary prophylaxis in sickle cell disease: is it feasible? Is it effective?
AB  - Consideration of primary prophylaxis to prevent complications of sickle cell
      disease (SCD) requires a clear understanding of the earliest manifestations of
      SCD-related organ injury, a reliable clinical or laboratory tool to detect organ
      dysfunction, and evidence that an intervention instituted in the presymptomatic
      state can mitigate disease progression. This review examines the pathophysiology
      of SCD in organs that may be potential targets for intervention, our current
      capacity to evaluate early SCD manifestations, results of clinical trials, and
      opportunities for future interventions.

PMID- 22160071
TI  - What is the evidence for using hydroxyurea for secondary stroke prevention?
AB  - A 10-year-old male patient with hemoglobin SS suffered a stroke at 7 years of age
      and was initially transfused at the time of presentation to lower the hemoglobin
      S concentration to < 30%. You are asked by the family if their child can be
      treated with oral hydroxyurea rather than monthly transfusions for the secondary
      prevention of strokes.

PMID- 22160072
TI  - Impact of iron assessment by MRI.
AB  - The use of magnetic resonance imaging (MRI) to estimate tissue iron was conceived
      in the 1980s, but has only become a practical reality in the last decade. The
      technique is most often used to estimate hepatic and cardiac iron in patients
      with transfusional siderosis and has largely replaced liver biopsy for liver iron
      quantification. However, the ability of MRI to quantify extrahepatic iron has had
      a greater impact on patient care and on our understanding of iron overload
      pathophysiology. Iron cardiomyopathy used to be the leading cause of death in
      thalassemia major, but is now relatively rare in centers with regular MRI
      screening of cardiac iron, through earlier recognition of cardiac iron loading.
      Longitudinal MRI studies have demonstrated differential kinetics of uptake and
      clearance among the difference organs of the body. Although elevated serum
      ferritin and liver iron concentration (LIC) increase the risk of cardiac and
      endocrine toxicities, some patients unequivocally develop extrahepatic iron
      deposition and toxicity despite having low total body iron stores. These
      observations, coupled with the advent of increasing options for iron chelation
      therapy, are allowing clinicians to more appropriately tailor chelation therapy
      to individual patient needs, producing greater efficacy with fewer toxicities.
      Future frontiers in MRI monitoring include improved prevention of endocrine
      toxicities, particularly hypogonadotropic hypogonadism and diabetes.

PMID- 22160073
TI  - Real-world use of iron chelators.
AB  - Whereas RBC transfusion therapy is lifesaving in thalassemia, obligatory iron
      loading accompanies such treatment and chelation therapy to remove and detoxify
      iron resulting from these chronic transfusions must therefore be administered.
      Morbidity and mortality in thalassemia is linked closely to the adequacy of
      chelation. Three chelators are currently available worldwide-deferoxamine,
      deferasirox, and deferiprone, although the latter is available in North America
      only in research protocols and compassionate use programs. These chelators can be
      used as monotherapy or in combination, although only the combination of
      deferiprone and deferoxamine has been extensively studied to date. Several
      factors, including chelator availability and its properties, drug tolerability,
      degree of organ-specific iron loading, ongoing transfusional iron burden, and
      patient preference, must be considered in the design of optimal, individualized
      chelation regimens, and these factors must periodically be reviewed and chelation
      adjusted accordingly. Ultimately, comparative effectiveness trials may help to
      determine the ideal strategy (eg, intensification of monotherapy or combined
      therapy including agents and doses) for treating various scenarios of organ
      specific iron loading.

PMID- 22160074
TI  - Targeted therapeutic strategies for fetal hemoglobin induction.
AB  - Increased levels of fetal hemoglobin (HbF) can ameliorate the severity of the
      beta-hemoglobin disorders, sickle cell disease (SCD) and beta-thalassemia, which
      are major sources of morbidity and mortality worldwide. As a result, there has
      been a longstanding interest in developing therapeutic approaches for inducing
      HbF. For more than 3 decades, the majority of HbF inducers developed were based
      on empiric observations and have had limited success. Recently, human genetic
      approaches have provided insight into previously unappreciated regulators of the
      fetal-to-adult hemoglobin switch and HbF silencing, revealing molecular targets
      to induce HbF. This article reviews these developments and discusses how
      molecules including BCL11A, KLF1, MYB, SOX6, miRNAs 15a and 16-1, and histone
      deacetylase 1 and 2 (HDAC1/2) could be important targets for HbF induction in
      humans. The current understanding of how these molecules function and the
      benefits and drawbacks of each of these potential therapeutic targets are also
      examined. The identification of these regulators of HbF expression is extremely
      promising and suggests that rationally designed approaches targeting the very
      mechanisms mediating this switching process could lead to better, less toxic, and
      more effective strategies for HbF induction.

PMID- 22160075
TI  - Immunoregulatory effects of stored red blood cells.
AB  - Some clinical studies have identified potential adverse patient outcomes
      associated with RBC storage length. This may in part be due to the release of
      potentially hazardous bioactive products that accumulate during storage and are
      delivered at high concentrations during transfusion. In this situation, a
      proinflammatory tissue microenvironment may be established that can alter
      immunoregulatory mechanisms. This review highlights some of the potential
      immunomodulatory effects of stored RBCs that may be responsible for adverse
      transfusion reactions.

PMID- 22160076
TI  - Immunomodulatory mediators in platelet transfusion reactions.
AB  - Our appreciation of the roles that platelets play in vascular biology is
      constantly expanding. One of the major roles of platelets is in initiating and
      accelerating immune responses. Platelet transfusion may be associated with
      adverse inflammatory outcomes manifested as fever, discomfort, tachycardia, and
      respiratory issues. This may in part be due to immune mediators either expressed
      by activated platelets or released into the platelet media during platelet
      storage. This review will highlight some more recent knowledge gained regarding
      the platelet storage lesion and potential mediators of platelet transfusion
      reactions.

PMID- 22160078
TI  - Dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is a multisystem inherited syndrome exhibiting marked
      clinical and genetic heterogeneity. In its classic form, it is characterized by
      mucocutaneous abnormalities, BM failure, and a predisposition to cancer. BM
      failure is the principal cause of premature mortality. Studies over the last 15
      years have led to significant advances, with 8 DC genes (DKC1, TERC, TERT, NOP10,
      NHP2, TIN2, C16orf57, and TCAB1) having been characterized. Seven of these are
      important in telomere maintenance either because they encode components of the
      telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the
      shelterin complex (TINF2). DC is therefore principally a disease of defective
      telomere maintenance and patients usually have very short telomeres. The genetic
      advances have led to the unification of DC with several other disorders,
      including the severe multisystem disorders Hoyeraal-Hreidarsson and Revesz
      syndromes, as well as a subset of patients with aplastic anemia, myelodysplasia,
      leukemia, and idiopathic pulmonary fibrosis. This wide spectrum of diseases
      ranging from classic DC to aplastic anemia can be regarded as disorders of
      defective telomere maintenance-"the telomereopathies." These advances have
      increased our understanding of normal hematopoiesis and highlighted the important
      role of telomerase and telomeres in human biology. They are also facilitating the
      diagnosis (especially when presentation is atypical) and management of DC.

PMID- 22160077
TI  - Vascular effects of the red blood cell storage lesion.
AB  - Transfusion of RBCs is often clinically necessary--and life-saving--for anemic
      patients. RBCs can be stored for up to 42 days between the time of donation and
      the time of transfusion. For many years, investigators have studied the
      biochemical changes that occur in RBCs stored before transfusion (the RBC
      "storage lesion"). More recently, clinical studies have suggested that RBC units
      stored for long periods (often described as > 14-21 days) may mediate adverse
      effects in the recipient, leading to morbidity and mortality. Unfortunately,
      these effects are difficult to identify and study because there are no agreed
      upon mechanisms for these adverse events and few good assays to study them in
      individual transfusion recipients. We have proposed the hypothesis of
      insufficient NO bioavailability (INOBA) to explain the adverse events associated
      with transfusion of older RBC units. INOBA postulates that the combination of
      impaired NO production and increased NO scavenging by stored RBCs, together with
      reduced NO synthesis by dysfunctional endothelial cells, collectively reduce NO
      levels below a critical threshold in vascular beds. In this situation,
      inappropriate vasoconstriction occurs, leading to reduced blood flow and
      insufficient O(2) delivery to end organs. If confirmed, the INOBA hypothesis may
      lead to improved methods for blood storage and collection, as well as new
      screening and matching tools for blood donors and transfusion recipients.

PMID- 22160079
TI  - Diamond Blackfan anemia.
AB  - Mutations affecting genes encoding ribosomal proteins cause Diamond Blackfan
      anemia (DBA), a rare congenital syndrome associated with physical anomalies,
      short stature, red cell aplasia, and an increased risk of malignancy. p53
      activation has been identified as a key component in the pathophysiology of DBA
      after cellular and molecular studies of knockdown cellular and animal models of
      DBA and other disorders affecting ribosomal assembly or function. Other potential
      mechanisms that warrant further investigation include impaired translation as the
      result of ribosomal insufficiency, which may be ameliorated by leucine
      supplementation, and alternative splicing leading to reduced expression of a
      cytoplasmic heme exporter, the human homolog of the receptor for feline leukemia
      virus C (FVLCR). However, the molecular basis for the characteristic steroid
      responsiveness of the erythroid failure in DBA remains unknown. This review
      explores the clinical and therapeutic implications of the current state of
      knowledge and delineates important but as-yet-unanswered questions.

PMID- 22160080
TI  - Fanconi anemia.
AB  - Fanconi anemia (FA) is the most frequent inherited cause of BM failure (BMF).
      Fifteen FANC genes have been identified to date, the most prevalent being FANCA,
      FANCC, FANCG, and FANCD2. In addition to classical presentations with progressive
      BMF during childhood and a positive chromosome breakage test in the blood,
      atypical clinical and/or biological situations can be seen in which a FA
      diagnosis has to be confirmed or eliminated. For this, a range of biological
      tools have been developed, including analysis of skin fibroblasts. FA patients
      experience a strong selective pressure in the BM that predisposes to clonal
      evolution and to the emergence in their teens or young adulthood of
      myelodysplasia syndrome (MDS) and/or acute myeloid leukemia (AML) with a specific
      pattern of somatic chromosomal lesions. The cellular mechanisms underlying (1)
      the hematopoietic defect which leads to progressive BMF and (2) somatic clonal
      evolutions in this background, are still largely elusive. Elucidation of these
      mechanisms at the molecular and cellular levels should be useful to understand
      the physiopathology of the disease and to adapt the follow-up and treatment of FA
      patients. This may also ultimately benefit older, non-FA patients with aplastic
      anemia, MDS/AML for whom FA represents a model genetic condition.

PMID- 22160081
TI  - Relapsed/refractory diffuse large B-cell lymphoma.
AB  - Despite overall improvements in outcomes of diffuse large B-cell lymphoma
      (DLBCL), approximately one-third of patients will develop relapsed/refractory
      disease that remains a major cause of morbidity and mortality. Novel insights
      from gene-expression analyses have increased our understanding of chemotherapy
      resistance and yielded rational targets for therapeutic intervention to both
      prevent and treat relapsed/refractory DLBCL. The clinical approach to
      relapsed/refractory DLBCL should include high-dose therapy and autologous stem
      cell transplantation (HD-ASCT) with curative intent in patients without
      comorbidities. Results from the recently reported CORAL study suggest that
      patients refractory to rituximab-containing regimens have inferior outcomes with
      HD-ASCT. Ongoing efforts to improve ASCT include novel conditioning regimens and
      evaluation of maintenance approaches after ASCT. Unfortunately, because the
      majority of patients are not eligible for ASCT due to refractory disease or
      age/comorbidities, these approaches have limited impact. The large group of
      patients not eligible for ASCT have incurable disease and should be referred for
      clinical trials of rationally targeted agents.

PMID- 22160082
TI  - Aggressive B-cell lymphomas: a review of new and old entities in the WHO
      classification.
AB  - Aggressive B-cell lymphomas are clinically and pathologically diverse and reflect
      multiple pathways of transformation. The 2008 World Health Organization (WHO)
      classification reflects this complexity with the addition of several new entities
      and variants. Whereas MYC translocations have long been associated with Burkitt
      lymphoma (BL), deregulation of MYC has been shown to occur in other aggressive B
      cell lymphomas, most often as a secondary event. Lymphomas with translocations of
      both MYC and BCL2 are highly aggressive tumors, with a high failure rate with
      most treatment protocols. These "double-hit" lymphomas are now separately
      delineated in the WHO classification as B-cell lymphoma, unclassifiable, with
      features intermediate between diffuse large B-cell lymphoma (DLBCL) and BL. A MYC
      translocation is also found uncommonly in DLBCL, but the clinical consequences of
      this in the absence of a double hit are not yet fully delineated. Most recently,
      MYC translocations have been identified as a common secondary event in plasma
      cell neoplasms, seen in approximately 50% of plasmablastic lymphoma. Another area
      that has received recent attention is the spectrum of EBV-driven B-cell
      proliferations in patients without iatrogenic or congenital immunosuppression;
      most of these occur in patients of advanced age and include the EBV-positive
      large B-cell lymphomas of the elderly.

PMID- 22160083
TI  - Therapies for peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of
      disorders that, for the most part, are associated with a very poor prognosis. The
      standard therapy for PTCLs is CHOP (cyclophosphamide, doxorubicin, vincristine,
      and prednisone) or a comparable CHOP-like regimen that incorporates
      anthracyclines. With the exception of anaplastic lymphoma kinase-positive
      anaplastic large cell lymphoma (ALK(+) ALCL), the cure rate for PTCLs with CHOP
      is low, and limited evidence suggests that anthracyclines do not improve the
      prognosis. However, there is no compelling evidence that any other regimen or
      approach is superior. It remains challenging to compare alternative therapies or
      treatment strategies with CHOP because the majority of data are retrospective and
      include diverse patient populations. Recently, prospective studies have been
      initiated exclusively for PTCL, and in some, select histologic subtypes are
      evaluated in an effort to remove heterogeneity. Encouragingly, there have been
      several new therapies emerging with activity in PTCLs and exciting novel
      combinations under consideration that will hopefully move the field forward and
      improve outcome in this challenging group of diseases.

PMID- 22160084
TI  - Congenital sideroblastic anemias: iron and heme lost in mitochondrial
      translation.
AB  - The congenital sideroblastic anemias (CSAs) are an uncommon, diverse class of
      inherited hematopoietic disorders characterized by pathological deposition of
      iron in the mitochondria of erythroid precursors. In recent years, the genetic
      causes of several clinically distinctive forms of CSA have been elucidated, which
      has revealed common themes in their pathogenesis. In particular, most, if not
      all, can be attributed to disordered mitochondrial heme synthesis, iron-sulfur
      cluster biogenesis, or pathways related to mitochondrial protein synthesis. This
      review summarizes the clinical features, molecular genetics, and pathophysiology
      of each of the CSAs in the context of these pathways.

PMID- 22160085
TI  - Unraveling mechanisms regulating systemic iron homeostasis.
AB  - Systemic iron balance must be tightly regulated to prevent the deleterious
      effects of iron deficiency and iron overload. Hepcidin, a circulating hormone
      that is synthesized by the liver, has emerged as a key regulator of systemic iron
      homeostasis. Hepcidin inhibits the absorption of dietary iron from the intestine
      and the release of iron derived from red blood cells from macrophages. Therefore,
      variation in hepcidin levels modifies the total amount of iron stored in the body
      and the availability of iron for erythropoiesis. The production of hepcidin by
      the liver is modulated by multiple physiological stimuli, including iron loading,
      inflammation, and erythropoietic activity. Investigation of the functions of the
      gene products mutated in inherited iron disorders using tissue-culture systems
      and animal models has provided valuable insights into the mechanisms by which
      these hepcidin responses are mediated. This review focuses on recent advances in
      our understanding of the molecular mechanisms underlying the regulation of
      systemic iron homeostasis.

PMID- 22160086
TI  - The hepcidin-ferroportin system as a therapeutic target in anemias and iron
      overload disorders.
AB  - The review summarizes the current understanding of the role of hepcidin and
      ferroportin in normal iron homeostasis and its disorders. The various approaches
      to therapeutic targeting of hepcidin and ferroportin in iron-overload disorders
      (mainly hereditary hemochromatosis and beta-thalassemia) and iron-restrictive
      anemias (anemias associated with infections, inflammatory disorders, and certain
      malignancies, anemia of chronic kidney diseases, and iron-refractory iron
      deficiency anemia) are also discussed.

PMID- 22160087
TI  - Genetics of myelodysplastic syndromes: new insights.
AB  - Myelodysplastic syndromes (MDS) are a heterogenous group of hematologic
      malignancies characterized by clonal expansion of BM myeloid cells with impaired
      differentiation. The identification of recurrent mutations in MDS samples has led
      to new insights into the pathophysiology of these disorders. Of particular
      interest is the recent recognition that genes involved in the regulation of
      histone function (EZH2, ASXL1, and UTX) and DNA methylation (DNMT3A, IDH1/IDH2,
      and TET2) are recurrently mutated in MDS, providing an important link between
      genetic and epigenetic alterations in this disease. The mechanism by which these
      mutated genes contribute to disease pathogenesis is an active area of research,
      with a current focus on which downstream target genes may be affected. Recent
      advances from sequencing studies suggest that multiple mutations are required for
      MDS initiation and progression to acute myeloid leukemia (AML). The past several
      years have yielded many new insights, but the complete genetic landscape of MDS
      is not yet known. Moreover, few (if any) of the findings are sufficiently robust
      to be incorporated into routine clinical practice at this time. Additional
      studies will be required to understand the prognostic implications of these
      mutations for treatment response, progression to AML, and survival.

PMID- 22160088
TI  - New ways to use DNA methyltransferase inhibitors for the treatment of
      myelodysplastic syndrome.
AB  - Ongoing analysis of the seminal AZA-001 study has taught many important lessons
      in the use of DNA methyltransferase (DNMT) inhibitors. The data emphasize the
      importance of patience in the use of these drugs, with several cycles required
      for the manifestations of hematologic responses. Improved survival in patients
      with high-risk myelodysplastic syndrome (MDS) treated with azacitidine extends to
      patients with any International Working Group-defined hematologic response;
      however, the benefit to patients with stable disease is less clear. A great deal
      remains to be learned about the optimal dosing and scheduling of the DNMT
      inhibitors, alone and in combination. New information on the impact of DNMT
      inhibitors on the immune system and on stem cells will likely lead to novel uses
      of these drugs in MDS and other hematologic and nonhematologic malignancies.

PMID- 22160089
TI  - Immunomodulating drugs in myelodysplastic syndromes.
AB  - Based on immune mechanisms that appear to play an important role in the
      pathophysiology of at least part of the lower-risk myelodysplastic syndrome
      (MDS), the immunomodulating drug (IMID) thalidomide and its derivative
      lenalidomide (LEN) have been used in MDS, principally in lower-risk MDS. LEN has
      become the first-line US Food and Drug Administration (FDA)-approved treatment
      for lower-risk MDS with 5q deletion (del5q), in which its main mechanism of
      action is probably a direct cytotoxic activity on the del5q clone. This possibly
      specific effect is currently being investigated in higher-risk MDS-and even acute
      myeloid leukemia (AML)-with del5q, but LEN has also demonstrated some efficacy in
      MDS and AML without del5q. Thalidomide also has some activity in lower-risk MDS
      without del5q, but its side effects limit its practical use in these patients.

PMID- 22160090
TI  - Job stress and job satisfaction of physicians in private practice: comparison of
      German and Norwegian physicians.
AB  - PURPOSE: This study examined job satisfaction and job stress of German compared
      to Norwegian physicians in private practice. METHODS: A representative sample of
      physicians in private practice of Schleswig-Holstein, Germany (N = 414) and a
      nationwide sample of Norwegian general practitioners and private practice
      specialists (N = 340) were surveyed in a cross-sectional design in 2010. The
      questionnaire comprised the standard instruments "Job Satisfaction Scale (JSS)"
      and a short form of the "Effort-Reward Imbalance Questionnaire (ERI)". RESULTS:
      Norwegian physicians scored significantly higher (<0.01) on all items of the job
      satisfaction scale compared to German physicians (M 5.57, SD 0.74 vs. M 4.78, SD
      1.01). The effect size was highest for the items freedom to choose method (d =
      1.012), rate of pay (d = 0.941), and overall job satisfaction (d = 0.931). While
      there was no significant difference in the mean of the overall effort scale
      between German and Norwegian physicians, Norwegian physicians scored
      significantly higher (p < 0.01) on the reward scale. A larger proportion of
      German physicians (27.6%) presented with an effort/reward ratio beyond 1.0,
      indicating a risky level of work-related stress, compared to only 10.3% of
      Norwegian physicians. Working hours, effort, reward, and country differences
      accounted for 37.4% of the explained variance of job satisfaction. CONCLUSIONS:
      Job satisfaction and reward were significantly higher in Norwegian than in German
      physicians. An almost threefold higher proportion of German physicians exhibited
      a high level of work-related stress. Findings call for active prevention and
      health promotion among stressed practicing physicians, with a special focus on
      improved working conditions.

PMID- 22160092
TI  - Cytogenetic and molecular cytogenetic findings in giant dedifferentiated
      liposarcoma of the thigh.
AB  - Non-retroperitoneal dedifferentiated liposarcoma (DDLS) is relatively uncommon
      and its characterization at the molecular genetic level has been limited. We
      describe the cyto-genetic and molecular cytogenetic findings of giant DDLS
      arising in the right thigh of an 83-year-old woman. Magnetic resonance imaging
      revealed a mass composed of two components with heterogeneous signal intensities,
      suggesting the coexistence of a fatty area and another soft tissue component. A
      wide resection of the tumor was performed. The resected, grossly heterogeneous
      mass, measuring 26x18x8 cm, was histopathologically composed of a well
      differentiated liposarcomatous component transitioning abruptly into a
      dedifferentiated one. Cytogenetic analysis exhibited a complex karyotype with
      several numerical and structural alterations, including ring and giant marker
      chromosomes. Metaphase-based comparative genomic hybridization analysis showed
      high-level amplifications of 1q21-q25 and 12q13-q21. Interphase fluorescence in
      situ hybridization analysis revealed MDM2 and CDK4 gene amplification in both the
      well-differentiated and dedifferentiated components. These findings indicate that
      DDLS of the extremity shares a similar genetic background to retroperitoneal
      DDLS.

PMID- 22160091
TI  - Concurrent drug eluting/bare metal stent implantation during percutaneous
      coronary intervention in target vessel: outcomes and 1-year follow-up.
AB  - AIM: We aimed at analyzing the safety of concurrent drug eluting stent (DES)/bare
      metal stent (BMS) placement in the same target segment using the dataset of the
      German Drug Eluting Stent Registry (DES.DE). METHODS AND RESULTS: In DES.DE a
      total of 5,296 patients either received concurrent BMS/DES (n = 526; 9.9%) or
      DES/DES stenting (n = 4,770; 90.1%) in the same target segment (5,407 segments).
      Patient and clinical characteristics were essentially similar in both groups. ACS
      was a positive adjusted predictor of BMS/DES concurrent stenting (OR 1.52; 95% CI
      1.23-1.87) as was age (OR 1.14; 1.04-1.25). Negative predictors were in-stent
      stenosis (OR 0.49; 0.35-0.68), lesion length >20 mm (OR 0.62; 0.51-0.75), >85%
      stenosis prior to PCI (OR 0.68; 0.56-0.83) and cardiogenic shock (OR 0.29; 0.09
      0.93). The in-hospital mortality in patients receiving BMS/DES concurrent
      stenting was higher than in those receiving DES/DES placement (OR 2.61; 95% CI
      1.05-6.49). At the 12 months follow-up there were no statistical differences with
      respect to mortality (OR 0.94; 95% CI 0.55-1.61). However, the incidence of
      recurrent myocardial infarction (OR 1.86; 1.11-3.12) and target vessel
      revascularization (TVR) (OR 1.37; 1.06-1.76) was borderline to significantly
      higher in BMS/DES patients. Multivariable predictors of 1-year mortality were
      age, ACS, cardiogenic shock, renal insufficiency, PAD, heart failure and smoking.
      CONCLUSIONS: Concurrent BMS/DES stenting is associated with an increase in in
      hospital but not long-term mortality. Further, there was a significant increase
      in recurrent myocardial infarction and TVR, but absolute differences were low.

PMID- 22160093
TI  - Targeted endovascular temporary vessel occlusion with a reverse thermosensitive
      polymer for near-bloodless partial nephrectomy: comparison to standard surgical
      clamping techniques.
AB  - PURPOSE: To determine whether reversible blood flow interruption to a randomly
      chosen target region of the kidney may be achieved with the injection of a
      reverse thermoplastic polymer through an angiographic catheter, thereby
      facilitating partial nephrectomy without compromising blood flow to the remaining
      kidney or adding risks beyond those encountered by the use of hilar clamping.
      METHODS: Fifteen pigs underwent partial nephrectomy after blood flow interruption
      by vascular cross-clamping or injection of polymer (LumagelTM) into a segmental
      artery. Five animals were euthanized after surgery (three open and two
      laparoscopic resection, cross-clamping n = 2), and 10 (open resection, cross
      clamping n = 4) were euthanized after 6 weeks' survival. Blood specimens were
      obtained periodically, and angiogram and necropsy were performed at 6 weeks.
      RESULTS: Selective renal ischemia was achieved in all cases. Surgical resection
      time averaged 9 and 24.5 min in the open and laparoscopic groups, respectively.
      Estimated blood loss was negligible with the exception of one case where an
      accessory renal artery was originally overlooked. Reversal of the polymer to a
      liquid state was consistent angiographically and visually in all cases. Time to
      complete flow return averaged 7.4 and 2 min for polymer and clamping,
      respectively. Angiography at 6 weeks revealed no evidence of vascular injury.
      Laboratory data and necropsies revealed no differences between animals undergoing
      vascular clamping or polymer injection. CONCLUSION: Lumagel was as effective as
      vascular clamping in producing a near bloodless operative field for partial
      nephrectomy while maintaining flow to the uninvolved portion of the affected
      kidney.

PMID- 22160094
TI  - Endovascular treatment of blunt traumatic abdominal aortic occlusion with kissing
      stent placement.
AB  - Blunt traumatic abdominal aortic dissection is extremely rare and potentially
      deadly. We present the case of a 62-year-old man involved in a frontal car crash.
      After emergency undergoing laparotomy for bowel injuries, he was referred to our
      hospital due to acute ischemia of bilateral lower extremities on day 3 after the
      trauma. Computed tomography and aortography showed an aortobiiliac dissection
      with complete occlusion. This injury was successfully treated by endovascular
      treatment with "kissing"-technique stent placement, which appears to be a safe,
      effective, and minimally invasive treatment.

PMID- 22160095
TI  - Endovascular mechanical recanalisation after intravenous thrombolysis in acute
      anterior circulation stroke: the impact of a new temporary stent.
AB  - PURPOSE: Treatment of acute stroke by endovascular mechanical recanalisation
      (EMR) has shown promising results and continues to be further refined. We
      evaluated the impact of a temporary stent compared with our results using other
      mechanical devices. MATERIALS AND METHODS: We analysed clinical and radiological
      data of all patients who were treated by EMR after intravenous thrombolysis for
      acute carotid T- and middle-cerebral artery (M1) occlusions at our centre between
      2007 and 2011. A comparison was performed between those patients in whom solely
      the stent-retriever was applied (group S) and those treated with other devices
      (group C). RESULTS: We identified 14 patients for group S and 16 patients for
      group C. Mean age, National Institute of Health Stroke Scale score, and time to
      treatment were 67.1 years and 16.5 and 4.0 h for group S and 61.1 years and 17.6
      and 4.5 h for group C, respectively. Successful recanalisation (thrombolysis in
      cerebral infarction scores >=IIb) was achieved in 93% of patients in group S and
      56% of patients in group C (P < 0.05). Mean recanalisation times for M1
      occlusions were 23 min (group S) and 29 min (group C) and for carotid-T
      occlusions were 39 min (group S) and 50 min (group C), and 45% of the patients in
      group S and 33% in group C had a favourable outcome (Modified Rankin Scale score
      <=2). CONCLUSION: The findings suggest an improvement in recanalisation success
      by the application of a temporary stent compared with previously used devices.
      These results are to be confirmed by larger studies.

PMID- 22160096
TI  - Effect of simvastatin on the expression and regulation mechanism of
      apolipoprotein M.
AB  - Apolipoprotein M (ApoM) is a recently discovered human apolipoprotein
      predominantly present in high-density lipoprotein (HDL) in the plasma. Statins
      have effects on many HDL-associated apolipoproteins. However, it is unknown
      whether statins have effects on ApoM. In the present study, we investigated the
      effects of simvastatin on ApoM expression and the underlying mechanism(s).
      Simvastatin up-regulated hepatic ApoM mRNA and protein expression in mice. In
      HepG2 cells, simvastatin significantly enhanced ApoM mRNA and protein expression
      in a dose-dependent manner. Simvastatin increased hepatic hepatocyte nuclear
      factor-1alpha (HNF-1alpha) mRNA and reduced liver X receptor-alpha (LXRalpha)
      mRNA expression in mice. The simvastatin-induced up-regulation of ApoM was
      blocked by an HNF-1alpha inhibitor (UCDA) or an LXRalpha agonist (TO901317) in
      HepG2 cells which indicates that this effect is mediated via the regulation of
      HNF-1alpha and LXRalpha. In conclusion, simvastatin significantly up-regulated
      ApoM expression in vivo and in vitro, which indicates that ApoM is another novel
      apolipoprotein regulated by simvastatin. The mechanism of this effect is related
      to the regulation of HNF-1alpha and LXRalpha.

PMID- 22160097
TI  - Prevalence of personality disorders using two diagnostic systems in psychiatric
      outpatients in Shanghai, China: a comparison of uni-axial and multi-axial
      formulation.
AB  - OBJECTIVE: To compare multi-axial (DSM-IV) with uni-axial diagnostic system (CCMD
      3, Chinese Classification and Diagnostic Criteria of Mental Disorders) as
      diagnostic methods to determine the prevalence of personality disorders (PDs) in
      Chinese psychiatric outpatients. METHOD: 3,075 outpatients were randomly sampled
      from clinical settings in China. CCMD-3 PDs were evaluated as per routine
      psychiatric practice. DSM-IV PDs were assessed using both self-reported
      questionnaire and structured clinical interview. RESULTS: The prevalence estimate
      for any type of PD in the total sample is 31.93% as reflected in the DSM-IV. This
      figure is nearly 110 times as large as the prevalence estimate for the CCMD-3.
      Only 9 outpatients were diagnosed with PD based on the CCMD-3. Amongst the 10
      forms of DSM-IV PDs, avoidant (8.1%), obsessive-compulsive (7.6%), paranoid
      (6.0%), and borderline (5.8%) PDs were the most prevalent subtypes. This study
      found that PDs are commonly associated with the following: (i) the younger aged;
      (ii) single marital status; (iii) those who were not raised by their parents;
      (iv) introverted personalities; (v) first-time seekers of psycho-counseling
      treatment; and (vi) patients with co-morbid mood or anxiety disorders.
      CONCLUSIONS: PDs are easily overlooked when the diagnosis is made based on the
      CCMD-3 uni-axial diagnostic system. However, it was found that personality
      pathology is common in the Chinese psychiatric community when using the DSM-IV
      classification system. Existing evidence suggest, at least indirectly, that there
      are important benefits of moving towards a multi-axial diagnostic approach in
      psychiatric practice.

PMID- 22160098
TI  - The effectiveness of poloxamer 407-based new anti-adhesive material in a
      laminectomy model in rats.
AB  - PURPOSE: In the laminectomy model in rats, to verify anti-adhesive effectiveness
      of the new material, a mixture composed of poloxamer 407, calcium chloride, and
      xanthorrhizol, we compared it with that of commercially used solution form anti
      adhesive agent GUARDIX-SL, Biorane. MATERIALS AND METHODS: A total of 108 Sprague
      Dawley rats (SD rats) were divided equally into three groups: negative control
      group (NCG), positive control group (PCG), and experimental group (EG). After
      exposing the dura on L4 level, we closed the wound shortly after hemostasis,
      after administering the anti-adhesive agent. To evaluate effectiveness, 18 SD
      rats from each group were killed after 1 week of rearing. Nine were examined by
      grading of gross adhesion and the other nine, by grading of histological
      adhesion. The degree of adhesion in the remainder of 18 SD rats in each group was
      examined with the same method after four weeks of rearing. RESULTS: Comparing the
      degree of adhesion after growth for 1 week, the gross and histological adhesion
      of the EG was lower than that of the NCG. There was no statistical significance
      in the gross score (P = 0.63), but there was statistical significance in the
      histological score (P = 0.04). The EG showed similar or improved degrees of
      adhesion in comparison with the PCG. In comparison after growth for 4 weeks,
      although gross adhesion of the EG was not significantly lower than the NCG,
      histological adhesion was remarkably low in the EG (P = 0.01). The EG showed
      similar or improved degrees of gross and histological adhesion in comparison to
      that of the PCG. (P = 0.20, 0.07). CONCLUSION: The new anti-adhesive material
      showed similar or improved effectiveness with the existing agents for commercial
      use. This result suggests that the new anti-adhesive material will be a
      successful candidate as a future product for clinical use.

PMID- 22160099
TI  - Thoracoscopic treatment for single level symptomatic thoracic disc herniation: a
      prospective followed cohort study in a group of 167 consecutive cases.
AB  - PROBLEM: Thoracic disc disease with radicular pain and myelopathic symptoms can
      have serious neurological sequelae. The authors present a relevant treatment
      option. METHODS: Data of patients with single level symptomatic thoracic disc
      herniation treated with thoracoscopic microdiscectomy were prospectively
      collected over a period of 10 years. Data collection included the preoperative
      status and the follow-up status was 6, 12 and 24 months after surgery for every
      patient. RESULTS: A total of 167 single level thorascoscopic discectomies without
      previous surgery on the level of the procedure were included in this study. The
      average preoperative duration of pain symptoms was 14.3 months, myelopathic
      symptoms were present for an average of 16.7 months before surgery. After the
      procedure pain scores measured with visual analog scale (VAS) decreased by 4.4
      points and the muscle strength improved by a mean of 4.6 points (American Spinal
      Injury Association ASIA motor score). After 2 years, 79% of the patients reported
      a excellent or good outcome for pain and 80% of the patients reported a excellent
      or good outcome for motor function. The overall complication rate was 15.6%.
      CONCLUSIONS: Thoracoscopic microdiscectomy for single level symptomatic disc
      herniation is a highly effective and reliable technique, it can be performed
      safely with low complication rate.

PMID- 22160100
TI  - Scientific journals and impact factors.

PMID- 22160101
TI  - Cytotoxic effects of nasal buserelin on nasal mucosal tissue in rabbits.
AB  - To investigate the cytotoxic effects of nasal buserelin on rabbit nasal mucosal
      tissue, twenty-four female rabbits were studied prospectively. The rabbits were
      divided into 4 groups including 6 rabbits. The rabbits' left noses were included
      in the all study groups: 150 MUg/puff/day of buserelin acetate was administered
      topically twice daily during 21, 42 and 63 days. Saline was administered
      topically twice daily to the left nasal cavity in the control group. The nasal
      septal mucosal stripe tissue was carefully removed from underlaying cartilage
      after sedation. HE staining, Masson's trichrome, toluidine blue and TUNEL
      staining were used to evaluate mucosal changes. Each preparation was investigated
      via apoptotic cells, and they were accounted. Kruskal-Wallis test was used to
      evaluate nonparametric comparison of apoptotic cells. Mononuclear cells have been
      raised in the sub-epithelial connective tissue, nucleuses of epithelial cells in
      the apical region were pyknotic, and apoptotic cells were determined on 21-day
      group. In the 42-day group, nasal epithelial tissue was similar to 21-day group
      and epithelial cells including pyknotic nucleus were present in this group, too.
      In the 63-day group, epithelial cells were light colored. Venous sinuses in the
      sub-epithelial connective tissue were wide but not congested and not raised
      collagen filaments. In the intra-epithelial tissue, some of cells were TUNEL (+).
      Apoptotic cells were fewer in the control group according to 21-day group. In 42-
      and 63-day groups, these cells were fewer than in 21-day group. Numerical
      difference was present between the groups, but statistical significance was not
      found between the groups. We concluded that nasal buserelin cytotoxicity was not
      potent in the nasal cavity in rabbits. We use nasal buserelin in all indications
      with confidence.

PMID- 22160102
TI  - Early combination treatment with intratympanic steroid injection in severe to
      profound sudden sensorineural hearing loss improves speech discrimination
      performance.
AB  - The objective of the study was to determine the therapeutic efficacy of early
      combined treatment with intratympanic steroid injection (ITSI) in patients with
      severe to profound sudden sensorineural hearing loss (SSNHL), who did not respond
      to initial systemic steroid treatment (SST). The study design included historical
      controlled trials (retrospective analysis for the SST group). Patients (n = 73;
      38 women and 35 men) diagnosed with severe to profound SSNHL at the time of their
      first visit in tertiary referral centers were recruited. Among these 73 patients,
      30 patients who showed no early response within a week after the start of initial
      SST were prospectively included as the ITSI group. ITSI was performed twice a
      week for two consecutive weeks. In contrast, 43 patients with the same condition
      who did not receive ITSI were retrospectively included as the SST group. For each
      group, pure-tone audiogram (PTA) and speech discrimination score (SDS) tests were
      performed before SST and more than 2 months after termination of treatment in
      each group. After termination of each treatment, the final average gain on PTA
      showed no significant difference between the two groups; however, the final
      average gain of SDS demonstrated a significantly better recovery in the ITSI
      group. ITSI as part of an early combined therapy represents an effective
      treatment in terms of the improvement of SDS in severe to profound SSNHL showing
      no early response to initial SST.

PMID- 22160103
TI  - Nickel phosphide-embedded graphene as counter electrode for dye-sensitized solar
      cells.
AB  - Nickel phosphide-embedded graphene, prepared by the hydrothermal reaction of red
      phosphorus, nickel chloride, and graphene oxide in a mixture of ethylene glycol
      water, is investigated as the counter electrode of DSSCs. It is demonstrated that
      the DSSC with the nickel phosphide-embedded graphene as the new counter electrode
      presents an excellent performance competing with that of the Pt electrode.

PMID- 22160104
TI  - Natal dispersal in relation to population density and sex ratio in the field
      vole, Microtus agrestis.
AB  - In a sample of 240 juvenile field voles 8% of the males and 22% of the females
      reached sexual maturity within their natal home range. Among individuals
      retrapped as adults, 58% of males and 23% of females had dispersed, i.e. had
      moved more than one home range diameter. The mean distance moved for males (58.5
      m) exceeded that for females (28.6 m). Male movement distances were negatively
      associated with total density, and with density of adult females, but not with
      male density. Female movements were not related to population density. There were
      no relation between sex ratio and distance moved. The distribution of distances
      moved for both males and females fit a geometrical distribution, suggesting the
      importance of competitive processes.

PMID- 22160105
TI  - Lizards reduce food consumption by spiders: mechanisms and consequences.
AB  - To determine the effect of lizards on webspider populations, we conducted a long
      term field experiment in the Bahamas. Numbers of spider individuals were about 3
      times higher in lizard-removal enclosures than in control enclosures with natural
      densities of lizards. Dietary analyses showed that lizards ate spiders and that
      lizard and spider diets overlapped substantially. Lizards reduced biomass of prey
      consumed by spiders; details indicated that they reduced biomass of large (> 4
      mm) prey consumed by spiders more than biomass of small (<=4 mm) prey. Similarly,
      lizards reduced biomass of large aerial arthropods caught in sticky traps but not
      biomass of small aerial arthropods. We found no evidence that the lizard effect
      on prey consumption by spiders was caused by a spatial shift from areas with high
      aerial arthropod abundance to areas with low aerial arthropod abundance. Lizards
      reduced adult female cephalothorax width and fecundity of spiders. In a separate
      experiment, food-supplemented spiders were more fecund than control spiders. This
      study indicates that the interaction between lizards and spiders includes both
      predation and competition for food.

PMID- 22160106
TI  - Local adaptation and host race formation of a gall-forming aphid in relation to
      environmental heterogeneity.
AB  - The process of host race formation in the aphid Tetraneura yezoensis is examined
      in relation to its population structure. T. yezoensis induces pouch galls on new
      leaves of Ulmus davidiana and U. laciniata. Its populations on the two host
      species are often sympatric. Fundatrices found on one elm species, when
      reciprocally transplanted to the other, suffered greatly reduced average fitness.
      This shows that aphid populations associated with the two elm species are
      genetically differentiated in physiological traits. Individual trees of each elm
      species showed large differences in susceptibility to gall formation and in bud
      burst time, and such between-tree variations were consistent over years.
      Overwintered eggs taken in early spring from four trees (two from each species)
      were incubated under the same temperature conditions. The average hatching time
      differed significantly even between populations from conspecific trees, and the
      sequence of egg hatching paralleled that of the leafing of those four trees. This
      between-tree difference in hatching time was consistent over years and was found
      to be genetic, showing that gene flow between aphid populations on separate trees
      is often restricted. The heterogeneity in host traits may have promoted the
      evolution of philopatry in this aphid. Of the fundatrices that hatched on a tree
      of one elm species, a few precent were preadapted to gall formation on the other
      elm species. This suggests that the formation of a new host race proceeds
      parapatrically under disruptive selection and at a low level of gene flow.
      Evidence was actually obtained that a small fraction of Tetraneura alates are
      passively transported and land on non-host plants.

PMID- 22160107
TI  - Ecological significance of light controlled seed germination in two contrasting
      tropical habitats.
AB  - The effects of temperature, photoperiod, phytochrome photoreversion and the
      response to a R/FR ratio gradient were investigated in seeds of four species from
      two contrasting tropical habitats; two species from a rain forest (Cecropia
      obtusifolia and Piper umbellatum) and two from a high altitude lava field covered
      by low vegetation (Buddleja cordata and Chenopodium ambrosioides). In the rain
      forest seed species the photoblastic response seems to be adapted to light
      quality changes due to canopy destruction, on the other hand, the lava field seed
      species seem to be adapted to instantaneous light stimulus such as would be
      produced by the sudden exposure of a buried seed to the soil surface light
      environment.

PMID- 22160108
TI  - Differences in environmental response between the sexes of the dioecious shrub
      Baccharis halimifolia (Compositae).
AB  - Baccharis halimifolia (Compositae) is a dioecious shrub which grows on the upland
      fringe of tidal marshes along the Atlantic and Gulf Coasts of North America. We
      examined the responses of the two sexes to variation in nutrient and moisture
      availability plant density, and defoliation. By growing plants from seedlings to
      flowering adults under various combinations of soil type, fertilization rate and
      plant density, we were able to establish different rates of plant growth and
      mortality. Plants grown at high density and low nutrient and water supply grew
      the least, incurrent the most mortality and showed a male-biased sex ratio (73%
      male). At low density with abundant nutrients and water, plants grew more,
      survived well, flowered frequently, and were female-biased (75% female). Changes
      in sex ratio were probably the result of sex-related mortality rather than sexual
      lability of the seedlings. While changes in sex ratio occurred under experimental
      conditions in the green-house, no evidence for differences in habitat utilization
      between the sexes were found in the field and the sex ratio (59% female) did not
      vary across habitats. In the marsh habitats we sampled where water and nutrients
      were apparently available, there was no evidence for differential mortality
      between the sexes. When defoliated (75% of leaf tissue), both sexes showed
      similar reductions in reproductive effort (number of flower heads/shoot). Our
      results indicate that differences between the sexes of Baccharis in their
      response to environmental growing conditions is an important ecological factor
      associated with the separation of male and female function into separate
      individuals.

PMID- 22160109
TI  - Patterns of growth, reproduction, defense, and herbivory in the dioecious shrub
      Baccharis halimifolia (Compositae).
AB  - Patterns of growth, reproduction, defense (leaf resin) and herbivory were
      compared between the sexes of the dioecious shrub Baccharis halimifolia
      (Compositae). Male plants possessed longer shoots and more tender leaves, grew
      faster, and flowered and senesced earlier than female plants. Levels of leaf
      nitrogen, water content, and acetone-soluble resin (shown to deter feeding by
      polyphagous insect herbivores) did not differ between male and female plants.
      When offered a choice between leaves from male and female plants, adults of two
      leaf beetles (Chrysomelidae), the monophagous Trirhabda bacharidis and the
      polyphagous Paria thoracica, both preferred to feed on male leaves. Similarly,
      the daily fecundity of older females of T. bacharidis was higher when they were
      fed leaves from male compared to female plants. However, adult survivorship and
      total fecundity of T. baccharidis did not differ between male and female leaf
      treatments. We attribute the feeding preference for and slight increase in
      fecundity on male plants to the tenderness of male leaves. Larvae of the fly
      Tephritis subpura (Tephritidae) fed exclusively in the sterile receptacle of male
      flower heads (85% infested), but the phenology was such that pollen production
      was not adversely affected. Larvae of two other flies Dasineura sp. and
      Contarinia sp. (Cecidomyiidae) occupied >95% of only female flower heads where
      they fed among and on the developing seeds. We conclude that foliage-feeding
      herbivores are unlikely candidates to explain the female-biased sex ratio (59%
      female) of B. halimifolia plants in the field, and that their preference for male
      plants is a result of plant characteristics (e.g. rapid growth) that have been
      selected by some other factor. However, our data on selective floral herbivory in
      B. halimifolia are in accord with the argument that dioecy reduces the
      inadvertent loss of flower parts of one sex when herbivores feed on flower parts
      of the opposite sex.

PMID- 22160110
TI  - Pollen limitation and distance-dependent fecundity in females of the clonal
      gynodioecious herb Glechoma hederacea (Lamiaceae).
AB  - Pollen movement is often restricted in natural populations, and insufficient
      pollination is a potential constraint on sexual reproduction in outcrossing
      species. Seed-set should decrease with increased distance from the pollen source
      in outcrossing plants. This prediction was tested using females of the clonal,
      gynodioecious herb Glechoma hederacea in three natural populations. In controlled
      pollinations, both hermaphrodites and females had similar high percentages of
      fruit-set and seed-set. In a natural population where a female clone was isolated
      from the nearest hermaphroditic clone by c. 100 m, fruit-set was low (1%). In
      another population where hemaphroditic clones were rare and female clones had a
      patchy distribution, fruit-and seed-set in females were pollen-limited and
      decreased with increased distance from the nearest pollen source. The estimated
      mean pollen dispersal distance was 5.9 m when calculated on fruit-set and 5.3 m
      when calculated on seed-set. The most frequent pollinators were bumblebees. The
      mean and median distances moved by pollinators between ramets were 0.13 m and
      0.05 m. In a third population where female clones were isolated from the nearest
      hermaphrodites by more than 200 m, fruit-set was 0%. After introduction of 16
      hermaphroditic ramets in the center of the female clone, fruit-set varied between
      0% and 100% in individual female ramets. Fruit-set decreased with increased
      distance from the pollen source. The mean and median pollen movement distances
      were 1.06 m and 0.54 m.

PMID- 22160111
TI  - Metabolic rates, food consumption and thermoregulation in seasonal
      acclimatization of the Cape porcupine Hystrix africaeaustralis.
AB  - Metabolic rates by means of oxygen consumption (VO(2)) at various ambient
      temperatures (T (a)) and food consumption as well as water intake and
      thermoregulation were compared between individuals of the Cape porcupine Hystrix
      africaeaustralis acclimated to T (a)=32 degrees C with a photoperiod of 16L:8D
      summer-acclimated and T (a)=10 degrees C; 8L:16D winter-acclimated. The lower
      critical temperature as well as overall minimal thermal conductance were lower
      for the winter-acclimated porcupines when compared to summer-acclimated ones,
      while VO(2) at the thermoneutral-zone was significantly (P<0.001) higher in the
      winter-acclimated porcupines. Dry matter intake, apparent digestible dry matter
      intake, gross digestible energy intake, as well as water intake, were
      significantly higher in the winter-acclimated porcupines. Yet, while dry matter
      intake increased 4 times in the winter-acclimated porcupines, apparent digestible
      dry matter increased only at a rate of 2.9 times. This difference is better
      reflected in terms of digestibility efficiency which in the winter-acclimated
      porcupines is only at a rate of 67.5% while in the summer-acclimated porcupines
      it is at a rate of 90%. From the results of this study, it is possible to assume
      that heat production in the winter-acclimated porcupines is partly increased by
      food intake. Increased heat production on the one hand, and a decrease in overall
      minimal thermal conductance on the other, seem to be important mechanisms in
      winter acclimatization of the Cape porcupine.

PMID- 22160112
TI  - Ecological and evolutionary importance of neighbors in the grass Anthoxanthum
      odoratum.
AB  - A field experiment was performed to estimate the relative importance of neighbors
      and the rest of the environment for the growth, mortality and reproductive output
      of cloned individuals of the perennial bunchgrass Anthoxanthum odoratum. Single
      cloned Anthoxanthum tillers (targets) were reciprocally transplanted between a
      xeric and a mesic grassland site with one of four neighbor treatments: (1) no
      neighbors, (2) Anthoxanthum neighbors transplanted from the xeric site, (3)
      Anthoxanthum neighbors from the mesic site, and (4) Holcus lanatus neighbors.
      Targets without neighbors had a twofold higher two year reproductive output (RO)
      than those with neighbors, but there was no difference among neighbor treatments.
      No overall site effect on two year RO was found, because the site with the
      highest mortality among targets produced larger plants, with more inflorescences.
      Neighborhood competition was more intense at the xeric site than at the mesic
      site. The effects of environmental and neighborhood variation on Anthoxanthum
      were additive, rather than interactive. Population origin did not affect target
      performance significantly. Anthoxanthum neighbors of different origin did respond
      differentially to transplant site. There was a strong target genotype x site
      interaction, but no genotype x neighborhood interaction.

PMID- 22160113
TI  - Simulated acid rain reduces the susceptibility of the European pine sawfly
      (Neodiprion sertifer) to its nuclear polyhedrosis virus.
AB  - The study dealt with the effect of simulated acid rain (both H(2)SO(4) and
      HNO(3); acidities of pH 4 and pH 3) on the susceptibility of the larvae of
      Neodiprion sertifer to its nuclear polyhedrosis virus. Scots pines growing in a
      subarctic area with low ambient pollution levels were irrigated with simulated
      acid rain during two summers. Neodiprion larvae fed with foliage from the
      experimental trees were infected with a dilute virus suspension. The acid
      treatment of host trees had a significant effect on the proportion of virus
      treated larvae alive 16 days after the virus application: there were almost no
      differences between the controls and the pH 4 irrigation group, but on the
      needles of pH 3-treated trees larval survival was twice as high as with other
      treatments. The direct spraying of acid water on the needles before they were fed
      to the larvae did not significantly affect the survival of virus infected larvae.
      Our results suggest that acid rain may reduce the susceptibility of Neodiprion
      larvae to virus disease via changes in the quality of pine foliage.

PMID- 22160114
TI  - Seed predation by insects in tropical mangrove forests: extent and effects on
      seed viability and the growth of seedlings.
AB  - Although insects are known to be important seed predators in most terrestrial
      forests, their role in marine tidal (mangrove) forests has not been examined.
      Surveys at 12 sites in tropical Australia showed that between 3.1 and 92.7
      percent of the seeds or propagules of 12 mangrove tree species had been attacked
      by insects. Seeds/propagules of six species (Avicennia marina, Bruguiera
      gymnorrhiza, B. parviflora, Heritiera littoralis, Xylocarpus australasicus and X.
      granatum) showed consistently high (>40%) levels of insect damage. Greater than
      99% of H. littoralis seeds were attacked by insect predators. The survival and
      subsequent growth in height and biomass of insect-damaged and non-damaged control
      seeds/propagules of eight mangrove species were compared in shadehouse
      experiments. Mangrove species fell into 4 groups with regard to the effect of
      insect predators on their seeds and seedlings. Xylocarpus australasicus and X.
      granatum had significantly decreased survival (X 48 and 70%) and growth in height
      (X 61 and 96%) and biomass (X 66 and 85%). Bruguiera parviflora showed decreased
      survival (X 59%), but there was no effect of insects on the growth of surviving
      propagules. In contrast, there was no effect of insect damage on the survival of
      seedlings of Avicennia marina and Bruguiera exaristata, but decreased growth in
      height (X 22 and 25%) and biomass (X 22 and 26%). Survival and growth of
      seedlings of Rhizophora stylosa and Bruguiera gymnorrhiza were not affected. The
      influence of insect seed predators on the survival and growth of seeds of
      mangrove species in forests will depend on the relative abundance of seed-eating
      crabs and intertidal position in mangrove forests.

PMID- 22160115
TI  - Patterns of coexistence in sexual and asexual species of Cnemidophorus lizards.
AB  - The lizard genus Cnemidophorus (family Teiidae) contains sexual as well as
      parthenogenetic species. The theoretical two-fold fitness advantage of asexuality
      does not translate into any obvious distributional or numerical superiority of
      the parthenogenic species in the southwestern US and northern Mexico where their
      ranges overlap. I tested the prediction that the genetically diverse sexual
      species should have a higher between-individual niche width than a similar
      sympatric asexual species by studying the prey in stomach contents of sympatric
      and allopatric populations of C. tigris (sexual) and C. sonorae (asexual) in
      southern Arizona. The expectation proved true for niche breadths based on both
      prey length and prey taxa categories. The within-individual component of niche
      breadth was not different between species. Meaningful comparisons between species
      in sympatry and allopatry are confounded by the uncontrolled differences in the
      availability and diversity of food items between sites. Before the generality of
      these results can be assessed the study should be repeated in other areas where
      sexual and asexual species are syntopic and of similar body size.

PMID- 22160116
TI  - Evolution of thermal physiology and growth rate between populations of the
      western fence lizard (Sceloporus occidentalis).
AB  - Hatchling Sceloporus occidentalis from northern populations (central Oregon) grow
      more slowly than hatchlings from southern populations (southern California) in
      nature. In this study, I determine whether this difference in growth rate results
      from differences in thermal environment and/or in thermoregulatory behavior. To
      determine the degree to which the thermal environment affects growth rate among
      populations, I reared hatchings from the northern and southern populations in a
      cycling thermal regime in one of three experimental treatments differing in
      access to radiant heat (6, 9, or 12 h radiant heat; remainder of 24 h at 15
      degrees C). I also measured the body temperature that each individual voluntarily
      selected over the course of the daily activity cycle. Growth rate varied
      positively with duration of access to radiant heat. Within the three treatments,
      individual growth rate was positively correlated with body temperature. Moreover,
      the difference in growth rate between the northern and southern populations was
      due in part to differences in behavior - individuals from northern populations
      selected lower body temperatures. I found that significant variation in body
      temperature was associated with family membership, suggesting that thermal
      physiology has a genetic basis. Moreover, growth rate was correlated with body
      temperature among families in each population suggesting a genetic correlation
      underlies the phenotypic correlations. Thus, genetically based variation in
      thermal physiology contributes to differences in growth rate among individuals
      within a population as well as to differences among populations.

PMID- 22160117
TI  - Effects of nectar volume and concentration on sugar intake rates of Australian
      honeyeaters (Meliphagidae).
AB  - Sugar intake rates of captive Australian honeyeaters (Meliphagidae) feeding at
      artificial flowers varied across species, and as a function of nectar volume and
      concentration within each species. Red Wattlebirds (Anthochaera carunculata, 110
      g), achieved higher intake rates than New Holland Honeyeaters (Phylidonyris
      novaehollandiae, 20 g), and both achieved higher rates than Eastern Spinebills
      (Acanthorhynchus tenuirostris, 10 g). These results reflect differences in bill
      and tongue dimensions as well as in body mass. Sugar intake rates for all three
      species increased with volume (5-50 MUl) at any given concentration (10-60%
      mass/mass sucrose). For a given volume, sugar intake rates peaked at intermediate
      concentrations: 40-50% for the two larger species, and 30-40% for the smallest
      species. Published studies for other nectarivores foraging at unlimited volume
      feeders also show optimal nectar concentrations of 30-50%. However, biophysical
      theory predicts optima at 20-26% for small volumes, and plants presumed to be
      adapted for bird-pollination often have dilute nectar (20-30%). To explore this
      discrepancy further, we presented New Holland Honeyeaters with a range of sucrose
      concentrations (10-50%) using two presentation schemes. In the first we varied
      concentration but kept volume constant, thus varying gross sugar reward available
      in each concentration. This gave maximum sugar intake rates at 50%. In the second
      we varied both volume and concentration so that gross sugar rewards were equal
      for all solutions, decoupling high concentrations and large sugar rewards. This
      gave optima at 20%. We argue that variation among plants in nature more closely
      resembles the latter, "equal sugar presentation" scheme, and therefore, that
      dilute nectars may indeed represent adaptations for bird pollination.

PMID- 22160118
TI  - Carbon isotope ratios are correlated with irradiance levels in the Panamanian
      orchid Catasetum viridiflavum.
AB  - Carbon isotope composition ((13)C/(12)C) in leaves of the Panamanian epiphytic
      orchid Catasetum viridiflavum were measured on individuals growing in canopies
      over a water surface to distinguish the effects of a change in source CO(2) and
      humidity from those of intercellular CO(2) concentration in determining isotopic
      composition. Carbon isotope ratios were observed to vary by over 4 in response to
      changes in total daily photon flux (PFD, 400-700 nm). Changes in isotopic
      composition of source CO(2) or changes in humidity were not likely to have played
      a role in determining leaf isotopic composition. Observed changed in carbon
      isotope discrimination (Delta) of leaves experiencing different light levels
      ranged from 17 to 21. Because leaf nitrogen contents were similar among all
      orchids, we suggest that the carbon isotope discrimination data indicated that
      stomatal limitation to photosynthesis increased with increasing irradiance.

PMID- 22160119
TI  - Gas exchange and habitat selection in the aquatic salamanders Necturus maculosus
      and Cryptobranchus alleganiensis.
AB  - The standard metabolic rate (SMR) and critical O(2) tension (P(c)) of water
      breathing mudpuppies and hellbenders were determined at 20 degrees  C using open
      system respirometry. Both species are metabolic O(2) regulators, although the
      P(c) of hellbenders (90 mmHg) is much higher than that of mudpuppies (40 mmHg).
      The SMR of the two species in water saturated with air was similar (19.5 and 20.0
      MUl O(2)/g.h for Cryptobranchus and Necturus, respectively) and not different
      from that of salamanders in general. Both species were able to survive for at
      least 5-11 days in severely hypoxic water (9-10 mmHg) by breathing air,
      indicating that the lungs are functional accessory respiratory structures.We
      conclude that hellbenders are restricted to relatively cool and flowing waters
      because of their limited gas exchange capabilities, particularly with regard to
      their limited aerobic scope for activity and slow recovery from exercise.
      Necturus maculosus is much more tolerant of hypoxia, but it is not known if they
      can inhabit areas were hypoxia is combined with hypercarbia.

PMID- 22160120
TI  - A reexamination of hilltopping in Euphydryas editha.

PMID- 22160121
TI  - Olfactory conditioning during the recruitment process in a leaf-cutting ant.
AB  - During recruitment, workers of Acromyrmex lundi are conditioned to the odor of
      the food fragment initially carried by the scout worker. The learned odor cue is
      used as a decision criterion during food collection.

PMID- 22160122
TI  - Variation in the use of orchid extrafloral nectar by ants.
AB  - The relation between ant-plant specificity and the use of host plants as a
      resource was investigated in the facultative, myrmecophytic orchid, Caularthron
      bilamellatum (Rchg.f.) Schult. Using stable isotopes, we determined the portion
      of the ants' diets derived from host plants. We documented that six ant species
      inhabiting the orchid: (1) derived nutritional benefit from host orchids, and (2)
      had species-specific levels of extrafloral nectar use. Proportionate contribution
      of extrafloral nectar to ant diets ranged from 11 to 48%. These results
      demonstrate extreme interspecific differences in the nutritional benefits
      received by ants from host orchids. Interspecific differences in nutritional
      benefits from orchid nectar may be affected by colony size, nutritional needs,
      behavioral ecology of the ants, and the abundance of alternate food sources.

PMID- 22160123
TI  - Amphipods on seaweeds: partners or pests?
AB  - Herbivorous marine amphipods have been implicated as important grazers on
      filamentous and ephemeral algae, and thus as beneficial to macrophytes in
      reducing overgrowth by epiphytic competitors. In North Carolina, USA, amphipods
      comprise 97% of all macroscopic animals inhabiting the abundant brown seaweed
      Sargassum filipendula, and peak in abundance between late winter and early
      summer. I used outdoor tank experiments to test the species-specific impact of
      common phytal amphipods on the growth of Sargassum and its epiphytes. The results
      show that seaweed-associated amphipods are a trophically diverse group that could
      either increase or decrease host fitness depending on their feeding preferences.
      The amphipods Ampithoe marcuzii, Caprella penantis, and Jassa falcata each
      significantly reduced growth of epiphytes on Sargassum plants relative to
      amphipod-free controls, while Ericthonius brasiliensis had no significant effect
      on Sargassum or its epiphytes. However, amphipod grazing was not necessarily
      beneficial to Sargassum. A. marcuzii consumed Sargassum in one outdoor tank
      experiment, reducing its mass by 11%, while Sargassum plants without amphipods
      grew by 81%. Epiphytes (mostly diatoms and the filamentous brown alga Ectocarpus
      siliculosus) and detritus remained abundant on these plants suggesting that A.
      marcuzii preferred the host to its epiphytes. Similarly, when given simultaneous
      access to Sargassum and to several common foliose and filamentous epiphytes in
      the lab, A. marcuzii ate Sargassum almost exclusively. The other three amphipods
      ate no macroalgae. In contrast to A. marcuzii, C. penantis consistently reduced
      epiphytes with no negative effect on Sargassum. Thus the species composition of
      the amphipod fauna can determine whether these animals increase or decrease
      seaweed fitness.

PMID- 22160124
TI  - The relationship between seed dormancy, seed size and weediness, in Crepis
      tectorum (Asteraceae).
AB  - I examined the germination characteristics of weed and outcrop populations of
      Crepis tectorum to test the hypothesis that the presumably more ephemeral weed
      habitat favors the highest levels of seed dormancy. The winter annual habit
      characterizing most plants of this species was reflected in a rapid germination
      of seeds sown in late summer. A slightly higher fraction of surface-sown seeds of
      weed plants delayed germination. Buried seeds of weed plants also survived better
      than seeds produced by plants in most outcrop populations, supporting the idea
      that weediness favors seed dormancy and a persistent seed bank. However, the
      differences in seed dormancy between the two ecotypes were small and not entirely
      consistent. Furthermore, high levels of seed dormancy were induced during burial
      in the outcrop group, suggesting that there is a potential for a dormant seed
      population in this habitat as well. Demographic data from one of the outcrop
      populations verified the presence of a large between-year seed bank. Possible
      environmental factors favoring seed dormancy in outcrop populations are
      discussed. The unusually large seeds of weedy Crepis contrasts with the
      relatively small difference in seed dormancy between the two ecotypes.

PMID- 22160125
TI  - Role of plant abundance in determining the abundance of herbivorous insects.
AB  - The proposal (Gaston and Lawton 1988a, b) that small species of insects are more
      abundant because they have lower per capita resource requirements than large
      species does not hold for aphids (Dixon 1990a). There are good theoretical
      grounds, supported by empirical data, for the suggestion that host specific
      aphids that live on uncommon plants incur great losses in finding their host
      plants and as a consequence have a lower realized r ( m ) and are rarer than
      aphids living on common plants. This is also likely to apply to other organisms
      that are host specific and 'time-limited' dispersers.

PMID- 22160126
TI  - Effects of larval diet on myrmecophilous qualities of Polyommatus icarus
      caterpillars (Lepidoptera: Lycaenidae).
AB  - Fourth instar larvae of Polyommatus icarus maintain myrmecophilous associations
      with ants. In laboratory experiments, the attractiveness of larvae reared on
      foliage of the tree Robinia pseudacacia was significantly reduced compared with
      caterpillars fed with herbaceous Fabaceae. The ability to secrete
      carbohydraterich liquids from the dorsal nectary organ was also strongly reduced,
      while the function of the tentacle organs remained unaffected. The reductions in
      attractiveness and secretion abilities are caused by the food quality itself and
      not by secondary effects such as reduced larval size. The ecological significance
      of the results are discussed with respect to facultatively and obligately
      myrmecophilous lycacnids.

PMID- 22160127
TI  - Dispersal and predation in alien Acacia.
AB  - I investigated seed removal in the litter layer of alien Acacia stands at
      bimonthly intervals throughout one year. Both ants (dispersers) and rodents
      (predators) removed significant quantities of seeds and may compete for seeds in
      low density Acacia stands. Seed removal from depots was greatest prior to seed
      fall (Sept.-Nov.) and lowest during seed-fall (Jan.-Mar.). As rodents may consume
      a large proportion of the annual seed production at low Acacia densities, I
      propose that ants have played a critical role in accumulating Acacia seed banks.

PMID- 22160128
TI  - Complete genome sequence of mandarin decline Citrus tristeza virus of the
      Northeastern Himalayan hill region of India: comparative analyses determine
      recombinant.
AB  - The complete genome sequence of a mandarin (Citrus reticulata) decline CTV
      isolate, Kpg3, of the Darjeeling hills of the Northeastern Himalayan region of
      India is reported for the first time. The complete Kpg3 genome has 19253 nt, and
      its nucleotide sequence identity ranged from 79% with the Florida CTV isolate T36
      to 94% with the Israel isolate VT, whereas its identity to B165, the other Indian
      isolate, was 89%. Phylogenetic analysis indicated that the Kpg3 genome is closely
      related to isolate VT and distantly to T36 and B165. Recombination analysis
      indicated that Kpg3 is recombinant and originated through multiple recombination
      events in which parts of the genome were exchanged between divergent CTV
      sequences.

PMID- 22160129
TI  - Genetic diversity in the 3'-terminal region of papaya ringspot virus (PRSV-W)
      isolates from watermelon in Oklahoma.
AB  - The 3'-terminal region (1191 nt) containing part of the NIb gene, complete coat
      protein (CP) and poly-A tail of 64 papaya ringspot virus (PRSV-W) isolates
      collected during 2008-2009 from watermelon in commercial fields of four different
      counties of Oklahoma were cloned and sequenced. Nucleotide and amino acid
      sequence identities ranged from 95.2-100% and 97.1-100%, respectively, among the
      Oklahoman PRSV-W isolates. Phylogenetic analysis showed that PRSW-W isolates
      clustered according to the locations where they were collected within Oklahoma,
      and each cluster contained two subgroups. All subgroups of Oklahoman PRSV-W
      isolates were on separate branches when compared to 35 known isolates originating
      from other parts of the world, including the one reported previously from the
      USA. This study helps in our understanding about the genetic diversity of PRSV-W
      isolates infecting cucurbits in Oklahoma.

PMID- 22160130
TI  - Etoposide, vincristine, doxorubicin and dexamethasone (EVAD) combination
      chemotherapy as second-line treatment for advanced AIDS-related Kaposi's sarcoma.
AB  - OBJECTIVE: To evaluate through retrospective analysis the efficacy and toxicity
      of combination chemotherapy with etoposide, vincristine, doxorubin and
      dexamethasone (EVAD) as second-line therapy in patients with advanced AIDS
      related Kaposi's sarcoma (AIDS-KS) after failure of first-line chemotherapy.
      METHODS: Eighty-eight patients with poor-risk AIDS-KS were treated intravenously
      with combination chemotherapy with EVAD; etoposide at a dose of 100 mg/m(2) on
      three consecutive days, vincristine 1.4 mg/m(2) with a maximum single dosage of
      2.0 mg on day one, doxorubicin 30 mg/m(2) on day one and dexamethasone 40 mg on
      three consecutive days, with a three week cycle. All eligible patients had
      relapsed or progressed after prior two to six cycles of combination chemotherapy
      with doxorubicin, bleomycin and vincristine (ABV) or bleomycin and vincristine
      (BV). RESULTS: Assessment of the response of all the patients was made. The
      overall objective response rate was 59.1% (95% CI 48.83-69.37%), with five
      complete responses and 47 partial responses. Twenty-six cases of stable disease
      and 10 of progressive disease were observed in the remaining patients. The median
      follow-up period was 27 months (range 8-52 months). The median time to
      progression was 6.80 months (95% CI 2.04-11.56 months), and the median overall
      survival was 14.24 months (95% CI 10.26-18.22 months). Leucopenia was seen in
      92.0% of patients, of which 20 patients had grade 3 and 12 had grade 4.
      Conclusions Combination chemotherapy with EVAD offers a new, active and safe
      therapeutic approach for the treatment of advanced AIDS-related KS.

PMID- 22160132
TI  - A sulfated polysaccharide, fucoidan, enhances the immunomodulatory effects of
      lactic acid bacteria.
AB  - Fucoidan, a sulfated polysaccharide contained in brown algae, has a variety of
      immunomodulatory effects, including antitumor and antiviral effects. On the other
      hand, lactic acid bacteria (LAB) also have immunomodulatory effects such as anti
      allergic effects. In this study, we demonstrated that fucoidan enhances the
      probiotic effects of LAB on immune functions. By using Peyer's patch cells and
      spleen cells in vitro, fucoidan amplified interferon (IFN)-gamma production in
      response to a strain of LAB, Tetragenococcus halophilus KK221, and this activity
      was abolished by desulfation of fucoidan. Moreover, this IFN-gamma response was
      abolished by interleukin (IL)-12 neutralization. These results indicate that
      fucoidan enhanced IL-12 production in response to KK221, resulting in promoting
      IFN-gamma production. In an in vivo study, Th1/Th2 immunobalance was most
      improved by oral administration of both fucoidan and KK221 to ovalbumin-immunized
      mice. These findings suggest that fucoidan can enhance a variety of beneficial
      effects of LAB on immune functions.

PMID- 22160131
TI  - Evaluation of genotoxic effects of lead in pottery-glaze workers using
      micronucleus assay, alkaline comet assay and DNA diffusion assay.
AB  - PURPOSE: We investigated genotoxic effects of occupational exposure to lead
      acetate in pottery-glaze ceramic workers. METHODS: The study was carried out in
      30 exposed workers and 30 matched controls, to whom several biochemical
      parameters-the blood lead (B-Pb; range: exposed, 41.68-404.77; controls, 12-52)
      and cadmium (B-Cd) level, the activity of delta-aminolevulinic acid dehydratase
      (ALAD), erythrocyte protoporphyrin (EP), the level of vitamin B(12) and folate in
      serum-were measured. The genotoxic effects were evaluated by the alkaline comet
      assay, the DNA diffusion assay and micronucleus test in peripheral blood
      lymphocytes. RESULTS: Subjects exposed to lead had significantly higher B-Pb
      level and, consequently, increased values of tail intensity (TI), frequency of
      apoptotic and necrotic cells, and frequency of micronuclei (MN). In contrast,
      their activity of ALAD, the level of vitamin B(12) and folate in serum were
      significantly lower compared to controls. Poisson regression analysis showed a
      significant correlation of profession, duration of exposure, smoking, level of
      cadmium in blood, ALAD and EP with primary DNA damage. A majority of primary
      damage repairs in a short period after exposure to a genotoxic agent. In
      addition, the influence of gender and level of vitamin B(12) and folate in serum
      MN frequency in exposed group was observed. CONCLUSIONS: In this study, DNA
      diffusion and micronucleus test showed higher influence of tested parameters to
      DNA damage. The results indicate a need for concomitant use of at least two
      different biomarkers of exposure when estimating a genetic risk of lead exposure.

PMID- 22160134
TI  - Concentrations of polybrominated diphenyl ethers in sediments from Jukskei River,
      Gauteng, South Africa.
AB  - This study determined concentration levels of polybrominated diphenyl ethers
      (PBDEs) in sediment samples collected from Jukskei River in South Africa. Final
      extracts, after concentration and dilution to 200 MUL were analyzed by injecting
      1 MUL in the GC-ECD and GC-MS. Results obtained showed good recoveries (73%-114%,
      with RSD < 17%). The concentrations of ?PBDEs in sediment for the seven sampling
      sites ranged from 0.92 to 6.76 ng g(-1) dry weight and total PBDEs with a total
      BDE sum of 23.85 ng g(-1) dry weights. Concentrations of PBDEs obtained in the
      present study are significantly lower than the values reported from developed
      countries.

PMID- 22160135
TI  - Determination of 4,4'-, 3,4'-, and 2,2'-diaminodiphenylethers in sediment samples
      from the sea using liquid chromatography-tandem mass spectrometry.
AB  - A selective method has been developed for determining the concentration of 4,4'-,
      3,4'-, and 2,2'-diaminodiphenylethers in sediment samples from the sea, using
      liquid chromatography/tandem mass spectrometry (LC/MS/MS). 4,4'
      diaminodiphenylether is a suspected toxic compound, and categorized as "Class I
      Designated Chemical Substance" in Japan. We have investigated the levels of 4,4'
      diaminodiphenylether in sediments to evaluate long-term water pollution. The
      methods detection limits for the 4,4'-, 3,4'-, and 2,2'-diaminodiphenylethers
      were 2.0, 1.7, and 4.8 ng/g-dry, respectively.

PMID- 22160133
TI  - From miracle fruit to transgenic tomato: mass production of the taste-modifying
      protein miraculin in transgenic plants.
AB  - The utility of plants as biofactories has progressed in recent years. Some
      recombinant plant-derived pharmaceutical products have already reached the
      marketplace. However, with the exception of drugs and vaccines, a strong effort
      has not yet been made to bring recombinant products to market, as cost
      effectiveness is critically important for commercialization. Sweet-tasting
      proteins and taste-modifying proteins have a great deal of potential in industry
      as substitutes for sugars and as artificial sweeteners. The taste-modifying
      protein, miraculin, functions to change the perception of a sour taste to a sweet
      one. This taste-modifying function can potentially be used not only as a low
      calorie sweetener but also as a new seasoning that could be the basis of a new
      dietary lifestyle. However, miraculin is far from inexpensive, and its potential
      as a marketable product has not yet been fully developed. For the last several
      years, biotechnological production of this taste-modifying protein has progressed
      extensively. In this review, the characteristics of miraculin and recent advances
      in its production using transgenic plants are summarized, focusing on such topics
      as the suitability of plant species as expression hosts, the cultivation method
      for transgenic plants, the method of purifying miraculin and future advances
      required to achieve industrial use.

PMID- 22160136
TI  - An efficient analytical method for analysis of spirotetramat and its metabolite
      spirotetramat-enol by HPLC.
AB  - Spirotetramat is a new compound which belongs to the chemical class of ketoenols.
      As per the available literature analysis of spirotetramat and its metabolites
      spirotetramat-enol is carried out by high pressure liquid chromatograph with mass
      spectrometry (HPLC-MS/MS). In this study we have standardized a method where
      analysis of both the compounds is carried out by HPLC. The extraction and cleanup
      of spirotetramat and its metabolites spirotetramat-enol was carried out by
      QuEChERS method. The cleaned up residues were estimated by HPLC equipped with a
      photo diode array detector at a wavelength of 250 nm. The mobile phase used was
      acetonitrile: water at a proportion of 40:60. The limit of quantification (LOQ)
      of the method was 0.05 mg kg(-1) for both spirotetramat and its metabolite
      spirotetramat-enol. The recoveries of both the compounds at the LOQ level were in
      the range of 72.72%-86.76% from mango and 74.82% to 86.92% from cabbage.

PMID- 22160137
TI  - Dissociable role of tumor necrosis factor alpha gene deletion in methamphetamine
      self-administration and cue-induced relapsing behavior in mice.
AB  - RATIONALE: During the development of addiction, addictive drugs induce transient
      and long-lasting changes in the brain including expression of endogenous
      molecules and alteration of morphological structure. Of the altered endogenous
      molecules, some facilitate but others slow the development of drug addiction.
      Previously, we have reported that tumor necrosis factor alpha (TNF-alpha) is a
      critical molecule among endogenous anti-addictive modulators using animal models
      of drug-conditioned place preference and drug discrimination. OBJECTIVES: Does
      targeted deletion of the TNF-alpha gene in mice affect methamphetamine (METH)
      self-administration, motivation to self-administer METH, cue-induced
      reinstatement of METH-seeking behavior, and food reinforcement or seeking
      behavior? METHODS: Both METH self-administration and reinstatement of drug
      seeking behavior and food self-delivery and food-seeking behavior were measured
      in TNF-alpha (-/-) and wild-type mice. RESULTS: There were an upward shift of
      dose responses to METH self-administration under a fixed ratio schedule of
      reinforcement and higher breaking points under a progressive ratio schedule of
      reinforcement in TNF-alpha knockout (TNF-alpha (-/-)) mice as compared with wild
      type mice. There was no significant difference in cue-induced reinstatement of
      METH-seeking behavior, food-maintained operant behavior, motivation to natural
      food, and cue-induced food-seeking behavior between TNF-alpha (-/-) and wild-type
      mice. CONCLUSION: TNF-alpha affects METH self-administration and motivation to
      self-administer METH but contributes to neither METH-associated cue-induced
      relapsing behavior nor food reward and food-seeking behavior. TNF-alpha may be
      explored for use as a diagnostic biomarker for the early stage of drug addiction.

PMID- 22160138
TI  - Suppression of endogenous PPARgamma increases vulnerability to methamphetamine
      induced injury in mouse nigrostriatal dopaminergic pathway.
AB  - RATIONALE: Methamphetamine is a commonly abused drug and dopaminergic neurotoxin.
      Repeated administration of high doses of methamphetamine induces programmed cell
      death, suppression of dopamine release, and reduction in locomotor activity.
      Previous studies have shown that pretreatment with peroxisome proliferator
      activated receptor gamma (PPARgamma) agonist reduced methamphetamine-induced
      neurodegeneration. OBJECTIVES: The purpose of this study was to examine the role
      of endogenous PPARgamma in protecting against methamphetamine toxicity. METHODS:
      Adeno-associated virus (AAV) encoding the Cre recombinase gene was unilaterally
      injected into the left substantia nigra of loxP-PPARgamma or control wild-type
      mice. Animals were treated with high doses of methamphetamine 1 month after viral
      injection. Behavioral tests were examined using rotarod and rotometer. In vivo
      voltammetry was used to examine dopamine release/clearance and at 2 months after
      methamphetamine injection. RESULTS: Administration of AAV-Cre selectively removed
      PPARgamma in left nigra in loxP-PPARgamma mice but not in the wild-type mice. The
      loxP-PPARgamma/AAV-Cre mice that received methamphetamine showed a significant
      reduction in time on the rotarod and exhibited increased ipsilateral rotation
      using a rotometer. The peak of dopamine release induced by local application of
      KCl and the rate of dopamine clearance were significantly attenuated in the left
      striatum of loxP-PPARgamma/AAV-Cre animals. Tyrosine hydroxylase immunoreactivity
      was reduced in the left, compared to right, nigra, and dorsal striatum in loxP
      PPARgamma/AAV-Cre mice receiving high doses of methamphetamine. CONCLUSION: A
      deficiency in PPARgamma increases vulnerability to high doses of methamphetamine.
      Endogenous PPARgamma may play an important role in reducing methamphetamine
      toxicity in vivo.

PMID- 22160139
TI  - Characterizing the effects of Eugenol on neuronal ionic currents and
      hyperexcitability.
AB  - RATIONALE: Eugenol (EUG, 4-allyl-2-methoxyphenol), the main component of
      essential oil extracted from cloves, has various uses in medicine because of its
      potential to modulate neuronal excitability. However, its effects on the ionic
      mechanisms remains incompletely understood. OBJECTIVES: We aimed to investigate
      EUG's effects on neuronal ionic currents and excitability, especially on voltage
      gated ion currents, and to verify the effects on a hyperexcitability-temporal
      lobe seizure model. METHODS: With the aid of patch-clamp technology, we first
      investigated the effects of EUG on ionic currents in NG108-15 neuronal cells
      differentiated with cyclic AMP. We then used modified Pinsky-Rinzel simulation
      modeling to evaluate its effects on spontaneous action potentials (APs). Finally,
      we investigated its effects on pilocarpine-induced seizures in rats. RESULTS: EUG
      depressed the transient and late components of I(Na) in the neurons. It not only
      increased the degree of I(Na) inactivation, but specifically suppressed the non
      inactivating I(Na) (I(Na(NI))). Its inhibition of I (Na(NI)) was reversed by
      tefluthrin. In addition, EUG diminished L-type Ca(2+) current and delayed
      rectifier K(+) current only at higher concentrations. EUG's effects on APs
      frequency reduction was verified by the simulation modeling. In pilocarpine
      induced seizures, the EUG-treated rats showed no shorter seizure latency but a
      lower seizure severity and mortality than the control rats. The EUG's effect on
      seizure severity was occluded by the I(Na(NI)) antagonist riluzole. CONCLUSION:
      The synergistic blocking effects of I (Na) and I(Na(NI)) contributes to the main
      mechanism through which EUG affects the firing of neuronal APs and modulate
      neuronal hyperexcitability such as pilocarpine-induced temporal lobe seizures.

PMID- 22160140
TI  - Sodium butyrate-induced DAPK-mediated apoptosis in human gastric cancer cells.
AB  - Epigenetic mechanisms of histone acetylation/deacetylation play an important role
      in the regulation of gene expression associated with the cell cycle and
      apoptosis. Recently, sodium butyrate, a histone deacetylase (HDAC) inhibitor, has
      been shown to exhibit anticancer effects via differentiation and apoptosis of
      cancer cells. Sodium butyrate may be a potential anticancer chemotherapeutic
      drug; however, the precise mechanism underlying the anticancer effects of sodium
      butyrate has not been clearly elucidated. In the present study, we investigated
      the role of death-associated protein kinase (DAPK) on the apoptosis of human
      gastric cancer cells induced by sodium butyrate. We observed that sodium butyrate
      induced apoptosis in human gastric cancer cells. Treatment with the HDAC
      inhibitor sodium butyrate increased the expression of caspase-3 and DAPK1/2 genes
      but decreased the expression of Bcl-2 in human gastric cancer cells. The
      expression of DAPK3, p53 and p21 were not altered by sodium butyrate treatment.
      Analysis of the general expression patterns revealed that sodium butyrate
      increased the expression of DAPK1/2 but decreased the expression of FAK and
      induced changes in the proliferation of apoptosis-related genes in human gastric
      cancer cells. These data suggest that DAPK expression prompts apoptosis by
      reducing the FAK protein level in sodium butyrate-induced apoptosis of human
      gastric cancer cells.

PMID- 22160141
TI  - Stress distribution in the temporo-mandibular joint discs during jaw closing: a
      high-resolution three-dimensional finite-element model analysis.
AB  - PURPOSE: This study aims at analysing the stresses distribution in the
      temporomandibular joint (TMJ) using a complete high-resolution finite element
      model (FE Model). This model is used here to analyse the stresses distribution in
      the discs during a closing jaw cycle. In the end, this model enables the
      prediction of the stress evolution in the TMJ disc submitted to various loadings
      induced by mandibular trauma, surgery or parafunction. MATERIALS AND METHODS: The
      geometric data for the model were obtained from MRI and CT scans images of a
      healthy male patient. Surface and volume meshes were successively obtained using
      a 3D image segmentation software (AMIRA((r))). Bone components of skull and
      mandible, both of joint discs, temporomandibular capsules and ligaments and
      dental arches were meshed as separate bodies. The volume meshes were transferred
      to the FE analysis software (FORGE((r))). Material properties were assigned for
      each region. Boundary conditions for closing jaw simulations were represented by
      different load directions of jaws muscles. The von Mises stresses distribution in
      both joint discs during closing conditions was analyzed. RESULTS: The pattern of
      von Mises stresses in the TMJ discs is non-symmetric and changed continuously
      during jaw movement. Maximal stress is reached on the surface disc in areas in
      contact with others bodies. CONCLUSIONS: The three-dimension finite element model
      of masticatory system will make it possible to simulate different conditions that
      appear to be important in the cascade of events leading to joint damage.

PMID- 22160143
TI  - Nasal septal packing: which one?
AB  - The aim of this study was to investigate the effects of four different types of
      nasal packs on pain, nasal fullness and postoperative bleeding following
      septoplasty. Prospective randomised double blind study was conducted. The study
      group included 119 patients who underwent endonasal septoplasty under general
      anaesthesia. Four types of nasal packing materials were utilized: (1) Merocel
      standard 8-cm nasal dressing without airway, (2) Doyle Combo splint (DCS), (3)
      Merocel in a glove finger and (4) Vaseline gauze. All packs were removed at the
      48th hour (+/-3 h) after the surgery. Three different variables were investigated
      following the surgical procedure: (1) pain, (2) nasal fullness and (3) bleeding
      after removal of the nasal packing material. DCS produced the greatest pain at
      the first and sixth postoperative hours. At the first postoperative day, the
      greatest pain score was reported for Merocel in the glove finger and the least
      for Merocel. The pain scores during the removal of the nasal packings were
      highest for Merocel and lowest for Merocel in the glove finger. DCS had the
      lowest nasal fullness score. Bleeding ratio was highest for Merocel, followed by
      Vaseline gauze, DCS and Merocel in the glove finger. Many different commercially
      available packing materials are presently used, each with inherent advantages and
      disadvantages. We evaluated the pain, nasal fullness and bleeding potential of
      four nasal packing materials and determined that Merocel had the highest pain
      potential during removal and the highest rate of bleeding following removal.

PMID- 22160144
TI  - Primary tumors and tumor-like lesions of the eustachian tube: a systematic review
      of an emerging entity.
AB  - Eustachian tube (ET) primary tumors and tumor-like lesions are rare diseases
      presenting with common ear, nose and throat symptoms. Pathology can range from
      developmental anomalies to high malignant neoplasms. Hence this review aimed at
      suggesting a classification and outline relevant aspects of ET primary tumors and
      tumor-like lesions, describing clinical findings, diagnostic management and
      therapeutic approaches. MEDLINE, CINAHL, OVIDSP, HIGHWIRE, and GOOGLE databases
      were searched from inception to July 2011 for relevant studies. Further papers
      were identified by examining the reference lists of all included. Sixty-five
      papers met the inclusion criteria, enclosing 78 cases. Case reports are
      increasing in the past few years. Benign lesions and tumor-like lesions of ET
      have been reported. Moreover, melanomas, carcinomas, and sarcomas can affect the
      ET as a primary site.

PMID- 22160145
TI  - Long-term efficacy of darunavir/ritonavir monotherapy in patients with HIV-1
      viral suppression: week 96 results from the MONOI ANRS 136 study.
AB  - OBJECTIVES: Long-term results at week 96 are needed to evaluate the capacity of
      the darunavir/ritonavir monotherapy strategy to maintain a sustained control of
      the HIV-1 viral load. METHODS: MONOI is a prospective, open-label, non
      inferiority, randomized, 96 week trial comparing darunavir/ritonavir monotherapy
      versus a darunavir/ritonavir triple-therapy strategy to maintain HIV-1 viral load
      suppression in HIV-1-infected patients. CLINICAL TRIAL REGISTRATION: NCT00412551.
      RESULTS: From 225 randomized patients, 219 patients reached the 48 week follow-up
      and 211 reached the 96 week follow-up (106 patients in the darunavir monotherapy
      arm and 105 in the darunavir triple-therapy arm). Baseline characteristics were
      well balanced between the two treatment groups. At week 96, in intent-to-treat
      analysis, 91/103 patients (88%, 95% CI 81-94) allocated to the
      darunavir/ritonavir monotherapy arm and 87/104 patients (84%, 95% CI 75-90)
      allocated to the darunavir triple-therapy arm achieved an HIV-1 viral load <50
      copies/mL, with no statistical difference between the two groups. Throughout the
      96 week follow-up, 66/112 patients (59%, 95% CI 49-68) and 79/113 patients (70%,
      95% CI 61-78) consistently had HIV-1 RNA <50 copies/mL with darunavir/ritonavir
      monotherapy and darunavir/ritonavir triple therapy, respectively. CONCLUSIONS:
      The MONOI study establishes darunavir/ritonavir monotherapy as durable and
      efficacious for maintaining virological suppression in HIV-1 patients.
      Darunavir/ritonavir monotherapy should be considered as a (tailored) treatment
      option for standard triple-therapy patients who have had a substantial period of
      viral suppression.

PMID- 22160146
TI  - Novel structurally related compounds reactivate latent HIV-1 in a bcl-2
      transduced primary CD4+ T cell model without inducing global T cell activation.
AB  - BACKGROUND: The latent reservoir of HIV-1 in resting memory CD4+ T cells is a
      major barrier to curing HIV-1 infection. Eradication strategies involve
      reactivation of this latent reservoir; however, agents that reactivate latent HIV
      1 through non-specific T cell activation are toxic. METHODS: Using latently
      infected Bcl-2-transduced primary CD4+ T cells, we screened the MicroSource
      Spectrum library for compounds that reactivate latent HIV-1 without global T cell
      activation. Based on the structures of the initial hits, we assembled ~50
      derivatives from commercial sources and mostly by synthesis. The dose-response
      relationships of these derivatives were established in a primary cell model.
      Activities were confirmed with another model of latency (J-Lat). Cellular
      toxicity and cytokine secretion were tested using freshly isolated human CD4+ T
      cells. RESULTS: We identified two classes of quinolines that reactivate latent
      HIV-1. Class I compounds are the Mannich adducts of 5-chloroquinolin-8-ol. Class
      II compounds are quinolin-8-yl carbamates. Most EC(50) values were in the 0.5-10
      MUM range. HIV-1 reactivation ranged from 25% to 70% for anti-CD3+ anti-CD28 co
      stimulation. All quinolin-8-ol derivatives that reactivate latent HIV-1 follow
      Lipinski's Rule of Five, and most follow the stricter rule of three for leads.
      After 48 h of treatment, none of the analogues induced detectable cytokine
      secretion in primary resting CD4+ T cells. CONCLUSIONS: We discovered a group of
      quinolin-8-ol derivatives that can induce latent HIV-1 in a primary cell model
      without causing global T cell activation. This work expands the number of latency
      reversing agents and provides new possible scaffolds for further drug development
      research.

PMID- 22160148
TI  - Lower brain diffusivity in postpartum period compared to late pregnancy: results
      from a prospective imaging study of multiple sclerosis patients.
AB  - INTRODUCTION: A positive correlation has been observed between multiple sclerosis
      (MS) disease activity status and the apparent diffusion coefficient (ADC) of the
      brain. Moreover, the relapse frequency of MS has been reported to decrease during
      pregnancy and increase postpartum. The aim of this study was to evaluate whether
      ADC histograms correlate with MS activity during pregnancy and postpartum, with a
      leading hypothesis that the ADC would increase postpartum compared to pregnancy.
      METHODS: Magnetic resonance imaging, as well as diffusion-weighted imaging, was
      performed in 19 patients with relapsing-remitting MS once during the third
      trimester and once 4-12 weeks postpartum. Brain tissue was extracted from
      nonbrain tissue with an automated computer program, and whole-brain histograms
      were generated. New or growing T2 lesions in postpartum images were counted on T2
      weighted images. RESULTS: In conventional brain magnetic resonance imaging, a
      significant increase in T2-lesion load was seen in postpartum images; 58% of
      patients showed signs of disease activity on their postpartum scan. Despite of
      this, and contrary to the original hypothesis, whole-brain ADC values were
      significantly lower in the postpartum period compared to the time of pregnancy.
      CONCLUSION: This is the first study to address the ADC of the brain during
      pregnancy and postpartum period. We hypothesize that the higher ADC values
      observed during pregnancy in this study reflect the physiological status of the
      cerebral vasculature during pregnancy (generalized vasodilatation of downstream
      resistance arterioles and an increase of endothelial permeability), which
      overwhelm the alterations in ADC values normally seen related to MS activity.

PMID- 22160149
TI  - Modelling study of prognostic indicators for patients with locally advanced or
      metastatic cancer identifies variables that predict short-term survival in
      palliative care.

PMID- 22160150
TI  - Hammering the point home: serologic testing costs more and harms more patients
      than other strategies for the diagnosis of active tuberculosis in India.

PMID- 22160151
TI  - Varenicline for 4 weeks prior to target quit date reduces prequit date smoking
      and increases 12-week abstinence.

PMID- 22160152
TI  - Antitumor and anti-angiogenic activities of Scutellaria barbata extracts in vitro
      are partially mediated by inhibition of Akt/protein kinase B.
AB  - The Akt pathway is considered a pivotal player in regulating cell survival,
      growth, migration and angiogenesis. Disruption of normal Akt/PKB/PTEN signaling
      frequently occurs in numerous types of human cancers. Therefore, this signaling
      pathway is regarded as an important target for effective cancer therapeutic
      strategies. In the present study, methanol extracts from Scutellaria barbata (S.
      barbata) were determined to be Akt/protein kinase B inhibitory, after screening a
      panel of 40 traditional Chinese herbs with the Fast Activated Cell-based ELISA
      (FACE) assay. S. barbata extracts were found to suppress the phosphorylation
      levels of Akt. This inhibition was Akt kinase-specific as it had no effect on
      PI3K, the upstream kinase of Akt, whereas the levels of phosphorylated Bad and
      FHKR, the two downstream targets of Akt, changed as the levels of Akt changed. S.
      barbata extracts also exhibited cytotoxicity against LoVo and human umbilical
      vein endothelial cells (HUVECs). Furthermore, this extract inhibited the process
      of in vitro angiogenesis of HUVECs on Matrigel. S. barbata may be a suitable
      alternative source with which to isolate small molecules for use as Akt kinase
      inhibitors.

PMID- 22160153
TI  - Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT in
      Germany: two sides of two different coins.

PMID- 22160154
TI  - Special issue: bioenergy.

PMID- 22160155
TI  - Three-staged correction of severe rigid idiopathic scoliosis using limited halo
      gravity traction.
AB  - INTRODUCTION: Despite the advantages of modern instrumentation techniques, the
      treatment of severe rigid idiopathic scoliosis could be very demanding. Traction
      can provide better, safer correction and minimize complications related to
      forceful intra-operative maneuvers; however, several side effects are associated
      with prolonged periods of traction. The aim of this work is to review the
      clinical and radiographic results of limited perioperative halo-gravity traction
      in severe rigid curves analyzing its efficacy, advantages and possible
      complications and comparing it to classic two staged corrections performed
      without traction. METHODS: A retrospective case control study including 47
      adolescents with severe rigid idiopathic scoliosis divided into two groups; a
      consecutive series of 21 patients who had a three-staged correction by an
      anterior release, 2 weeks of halo-gravity traction then posterior instrumentation
      (TRN group); compared to an earlier series of 26 consecutive patients treated
      without traction (SAP group). The average age was 18 years + 1 month and 16 years
      + 2 months, respectively. The average preoperative dorsal and lumbar curves for
      (TRN) group were 106.5 degrees  and 87 degrees , respectively, and for (SAP)
      group were 102 degrees  and 81 degrees , respectively. RESULTS: Patients were
      followed up for an average of 6 years (range 3-8 years). A significantly better
      correction was achieved in (TRN) group (average 59%) compared to (SAP) group
      (average 47%). At final follow-up, the loss of correction had an average of 8
      degrees  for (TRN) group and 11 degrees  for (SAP) group. A shorter hospital stay
      was found in (SAP) group; a shorter operative time was found in (TRN) group and
      there was no significant difference in blood loss, early or delayed
      complications. CONCLUSIONS: Limited halo-gravity traction is an efficient, safe
      modality in the treatment of severe rigid adolescent scoliosis. The application
      of gradual traction over a limited period of 2 weeks led to better correction,
      shorter operative time with no significant complications.

PMID- 22160156
TI  - Assessment of radiant temperature in a closed incubator.
AB  - In closed incubators, radiative heat loss (R) which is assessed from the mean
      radiant temperature (Tr) accounts for 40-60% of the neonate's total heat loss. In
      the absence of a benchmark method to calculate Tr--often considered to be the
      same as the air incubator temperature-errors could have a considerable impact on
      the thermal management of neonates. We compared Tr using two conventional methods
      (measurement with a black-globe thermometer and a radiative "view factor"
      approach) and two methods based on nude thermal manikins (a simple, schematic
      design from Wheldon and a multisegment, anthropometric device developed in our
      laboratory). By taking the Tr estimations for each method, we calculated
      metabolic heat production values by partitional calorimetry and then compared
      them with the values calculated from V(O2) and V(CO2) measured in 13 preterm
      neonates. Comparisons between the calculated and measured metabolic heat
      production values showed that the two conventional methods and Wheldon's manikin
      underestimated R, whereas when using the anthropomorphic thermal manikin, the
      simulated versus clinical difference was not statistically significant. In
      conclusion, there is a need for a safety standard for measuring TR in a closed
      incubator. This standard should also make available estimating equations for all
      avenues of the neonate's heat exchange considering the metabolic heat production
      and the modifying influence of the thermal insulation provided by the diaper and
      by the mattress. Although thermal manikins appear to be particularly appropriate
      for measuring Tr, the current lack of standardized procedures limits their
      widespread use.

PMID- 22160158
TI  - Extend the power of cellular models.

PMID- 22160159
TI  - Expression profile of microRNAs in fetal lung development of Sprague-Dawley rats.
AB  - As well-known regulators of gene expression, microRNAs (miRNAs) play an important
      role not only in cell proliferation and differentiation, but also in
      tumorigenesis and organ development. Furthermore, it is estimated that miRNAs may
      be responsible for regulating the expression of nearly one-third of the human
      genome. Simultaneously, in the clinic, with advances in neonatal care, a larger
      number of premature infants are being saved, and thus diseases of lung
      development, including bronchopulmonary dysplasia (BPD) have become more and more
      common. However, only a few miRNA studies have studied their connection with
      diseases of lung development. In our study, we used a miRNA microarray including
      more than 1891 capture probes to profile the expression of miRNAs at three time
      points of rat lung development [embryonic (E) Day 16 (E16), E19, E21]. miRNAs
      found to have consistent fold-changes (fold-change>2.0) during all three time
      points were selected and validated by real-time PCR. As a result, 167
      differentially expressed miRNAs were found during rat lung organogenesis,
      including 81 upregulated and 86 downregulated miRNAs. Seven miRNAs were selected
      and characterized by having a consistent >2-fold changes between all three
      groups. Among these 7 miRNAs, except for let-7a, the other 6 miRNAs (miR-1949,
      miR-125b-5p, miR-296, miR-93, miR-146b, miR-3560) are all first reported for the
      first time in lung development. Finally, due to the fact that they demonstrated
      higher fold changes, from these 7 miRNAs we selected miR-125b-5p, miR-296, miR
      93, miR-146b and miR-3560 for real-time PCR. We hypothesized that these newly
      identified miRNAs may play an important role in fetal lung development, and this
      experimental result could help us to further clarify the mechanism of normal lung
      development including the development of type II pneumocytes. This may provide a
      physiological basis for future research on diseases of lung development.

PMID- 22160157
TI  - Retrograde vesicle transport in the Golgi.
AB  - The Golgi apparatus is the central sorting and biosynthesis hub of the secretory
      pathway, and uses vesicle transport for the recycling of its resident enzymes.
      This system must operate with high fidelity and efficiency for the correct
      modification of secretory glycoconjugates. In this review, we discuss recent
      advances on how coats, tethers, Rabs and SNAREs cooperate at the Golgi to achieve
      vesicle transport. We cover the well understood vesicle formation process
      orchestrated by the COPI coat, and the comprehensively documented fusion process
      governed by a set of Golgi localised SNAREs. Much less clear are the steps in
      between formation and fusion of vesicles, and we therefore provide a much needed
      update of the latest findings about vesicle tethering. The interplay between Rab
      GTPases, golgin family coiled-coil tethers and the conserved oligomeric Golgi
      (COG) complex at the Golgi are thoroughly evaluated.

PMID- 22160160
TI  - High KIT and PDGFRA are associated with shorter patients survival in
      gastroenteropancreatic neuroendocrine tumors, but mutations are a rare event.
AB  - PURPOSE: (1) To test whether in genomewide expression profiling differentially
      expressed genes were also distinct on the protein level including KIT and PDGFRA
      (2) to correlate the expression with clinicopathological parameters (3) to
      identify activating mutations that might be eligible for tyrosine kinase
      inhibitor therapy by mutational analysis of tumors with high expression. METHODS:
      Gastroenteropancreatic neuroendocrine tumors (GEP NETs) from 119 patients were
      analyzed for protein expression of ten biomarkers. Mutational analysis of KIT
      (exon 9, 13, 11 and 17) and PDGFRA (exons 12 and 18) was performed on those
      samples that showed high protein expression. RESULTS: High KIT expression was
      observed in 13% of all specimens, PDGFRA in 33%, CK19 in 26%, CK7 in 2%, CK20 in
      5%, S100 in 6%, CD56 in 25%, Chromogranin in 55%, and Synapthophysin in 80%. High
      expression of KIT and PDGFRA was significantly correlated with shorter disease
      specific survival (P = 0.003, P = 0.018, respectively). In multivariate analysis
      expression of PDGFRA, radicality of surgical treatment and WHO grading influenced
      disease-specific 10-year survival independently (P = 0.032, P = 0.001 and P =
      0.008, respectively). Mutational analysis of highly expressed specimens (n = 51)
      reveals a novel mutation of KIT in exon 11 (K558N_V559insP) in a well
      differentiated metastatic pancreatic neuroendocrine tumor. CONCLUSIONS: High
      expression of KIT and PDGFRA was significantly correlated with shorter patients
      survival and could serve as prognostic marker. Mutations of the KIT gene might
      open new avenues for tyrosine kinase inhibitor therapy in a subset of patients
      with advanced pancreatic neuroendocrine tumors.

PMID- 22160161
TI  - Possible predictors of histopathological response to neoadjuvant
      chemoradiotherapy for rectal cancer.
AB  - PURPOSE: The response to neoadjuvant chemoradiotherapy (CRT) varies greatly in
      patients suffering from locally advanced rectal cancer. Our aim was to correlate
      the response to CRT with the pre-treatment expression of heat shock protein 90
      (Hsp90), small heat shock protein 16.2 (sHsp 16.2), phospho-Akt (p-Akt), growth
      hormone-releasing hormone receptor (GHRH-R) and heme-binding protein 2 (SOUL) in
      order to try to identify one or more as a predictive marker. MATERIALS AND
      METHODS: Sixty-nine patients receiving combined CRT for locally advanced rectal
      cancer were examined retrospectively. Surgical resection was carried out 6-9
      weeks following CRT. The histopathological response to neoadjuvant treatment was
      determined according to the modified Mandard score. Using immunohistochemistry,
      we investigated the relationship between the expression of the five cited
      proteins in the pre-operative samples as well as various clinical parameters and
      the histopathological regression of the tumors. RESULTS: Thirty-one patients
      (48%) were good responders, and 33 patients (52%) were found to respond poorly to
      neoadjuvant therapy. Among patients undergoing surgery 7 weeks following CRT,
      there were significantly more good responders than among patients who underwent
      surgery sooner (63% vs. 37%). High levels of expression of GHRH-R and Hsp90 were
      shown to be significantly correlated with minor or absent histological
      regression. CONCLUSIONS: GHRH-R and Hsp90 were found to be independent predictive
      factors of histopathological response to neoadjuvant RCT. Since GHRH-R
      antagonists and Hsp90 inhibitors are currently being tested as potential
      anticancer agents, our study implies the possible elaboration of an effective and
      individualized treatment of poor responders.

PMID- 22160162
TI  - Quinpirole elicits differential in vivo changes in the pre- and postsynaptic
      distributions of dopamine D2 receptors in mouse striatum: relation to cannabinoid
      1 (CB1) receptor targeting.
AB  - RATIONALE: The nucleus accumbens (Acb) shell and caudate-putamen nucleus (CPu)
      are respectively implicated in the motivational and motor effects of dopamine,
      which are mediated in part through dopamine D2-like receptors (D2Rs) and
      modulated by activation of the cannabinoid-1 receptor (CB1R). The dopamine
      D(2/D3) receptor agonist, quinpirole elicits internalization of D2Rs in isolated
      cells; however, dendritic and axonal targeting of D2Rs may be highly influenced
      by circuit-dependent changes in vivo and potentially influenced by endogenous
      CB1R activation. OBJECTIVE: We sought to determine whether quinpirole alters the
      surface/cytoplasmic partitioning of D2Rs in striatal neurons in vivo. METHODS: To
      address this question, we examined the electron microscopic immunolabeling of D2
      and CB1 receptors in the Acb shell and CPu of male mice at 1 h following a single
      subcutaneous injection of quinpirole (0.5 mg/kg) or saline, a time point when
      quinpirole reduced locomotor activity. RESULTS: Many neuronal profiles throughout
      the striatum of both treatment groups expressed the D2R and/or CB1R. As compared
      with saline, quinpirole-injected mice showed a significant region-specific
      decrease in the plasmalemmal and increase in the cytoplasmic density of D2R
      immunogold particles in postsynaptic dendrites without CB1R-immunolabeling in the
      Acb shell. However, quinpirole produced a significant increase in the
      plasmalemmal density of D2R immunogold in CB1R negative axons in both the Acb
      shell and CPu. CONCLUSIONS: Our results provide in vivo evidence for agonist
      induced D2R trafficking that is inversely related to CB1R distribution in
      postsynaptic neurons of Acb shell and in presynaptic axons in this region and in
      the CPu.

PMID- 22160166
TI  - Metal concentrations in surface sediments of Beyler reservoir (Turkey).
AB  - The accumulation of metals (Iron, Aluminium, Zinc, Copper, Manganese, Boron,
      Chromium, Nickel, Cadmium, Lead) was seasonally (November 2009 to July 2010)
      measured in sediment samples taken from different areas of Beyler reservoir which
      is an important water source for irrigation in West Black Sea region (Turkey).
      Metals in sediment samples were analyzed by ICP-OES. The difference between the
      stations except for Zn metal (p < 0.05) has not been considered as important and
      a statistical difference between seasons for Fe, Ni metals (p < 0.01) and Cu
      metal (p < 0.05) has been observed. The magnitude of metal concentrations in
      sediment was determined as Aluminium > Iron > Manganese > Zinc > Chromium >
      Copper > Boron > Nickel > Lead > Cadmium. Enrichment factor (EF) for all metals
      has been calculated (EF < 1). In the evaluation done by considering the EF
      values, it is seen that the metal concentrations found in the Beyler Dam Lake
      sediment stem from the natural composition of the sediment.

PMID- 22160165
TI  - Lateralized hippocampal effects of vasoactive intestinal peptide on learning and
      memory in rats in a model of depression.
AB  - RATIONALE: Findings of pharmacological studies revealed that vasoactive
      intestinal peptide (VIP) plays a modulatory role in learning and memory. A role
      of the peptide in the neurobiological mechanisms of affective disorders was also
      suggested. OBJECTIVE: The objectives are to study the involvement of VIP in
      learning and memory processes after unilateral and bilateral local application
      into hippocampal CA1 area in rats with a model of depression (bilateral olfactory
      bulbectomy--OBX) and to test whether VIP receptors could affect cognition.
      RESULTS: VIP (50 ng) and combination (VIP(6-28) 10 ng + VIP 50 ng) microinjected
      bilaterally or into the right CA1 area improved the learning and memory of OBX
      rats in shuttle-box and step-through behavioral tests as compared to the saline
      treated OBX controls. Left-side VIP microinjections did not affect the number of
      avoidances (shuttle box) and learning criteria (step through) as compared to the
      left-side saline-treated OBX controls. The administration of the combination into
      left CA1 influenced positively the performance in the step-through task. VIP
      antagonist (VIP(6-28), 10 ng) did not affect learning and memory of OBX rats.
      These findings suggest asymmetric effect of VIP on cognitive processes in
      hippocampus of rats with OBX model of depression. CONCLUSION: Our results point
      to a lateralized modulatory effect of VIP injected in the hippocampal CA1 area on
      the avoidance deficits in OBX rats. The right CA1 area was predominantly involved
      in the positive effect of VIP on learning and memory. A possible role of the PAC1
      receptors is suggested.

PMID- 22160164
TI  - Agomelatine (S20098) modulates the expression of cytoskeletal microtubular
      proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC.
AB  - RATIONALE: Agomelatine is described as a novel and clinical effective
      antidepressant drug with melatonergic (MT(1)/MT(2)) agonist and 5-HT(2C) receptor
      antagonist properties. Previous studies suggest that modulation of neuronal
      plasticity and microtubule dynamics may be involved in the treatment of
      depression. OBJECTIVE: The present study investigated the effects of agomelatine
      on microtubular, synaptic and brain-derived neurotrophic factor (BDNF) proteins
      in selected rat brain regions. METHODS: Adult male rats received agomelatine (40
      mg/kg i.p.) once a day for 22 days. The pro-cognitive effect of agomelatine was
      tested in the novel object recognition task and antidepressant activity in the
      forced swimming test. Microtubule dynamics markers, microtubule-associated
      protein type 2 (MAP-2), phosphorylated MAP-2, synaptic markers [synaptophysin,
      postsynaptic density-95 (PSD-95) and spinophilin] and BDNF were measured by
      Western blot in the hippocampus, amygdala and prefrontal cortex (PFC). RESULTS:
      Agomelatine exerted pro-cognitive and antidepressant activity and induced
      molecular changes in the brain areas examined. Agomelatine enhanced microtubule
      dynamics in the hippocampus and to a higher magnitude in the amygdala. By
      contrast, in the PFC, a decrease in microtubule dynamics was observed.
      Spinophilin (dendritic spines marker) was decreased, and BDNF increased in the
      hippocampus. Synaptophysin (presynaptic) and spinophilin were increased in the
      PFC and amygdala, while PSD-95 (postsynaptic marker) was increased in the
      amygdala, consistent with the phenomena of synaptic remodelling. CONCLUSIONS:
      Agomelatine modulates cytoskeletal microtubule dynamics and synaptic markers.
      This may play a role in its pharmacological behavioural effects and may result
      from the melatonergic agonist and 5-HT(2C) antagonist properties of the compound.

PMID- 22160167
TI  - Urinary stone size estimation: a new segmentation algorithm-based CT method.
AB  - OBJECTIVES: The size estimation in CT images of an obstructing ureteral calculus
      is important for the clinical management of a patient presenting with renal
      colic. The objective of the present study was to develop a reader independent
      urinary calculus segmentation algorithm using well-known digital image processing
      steps and to validate the method against size estimations by several readers.
      METHODS: Fifty clinical CT examinations demonstrating urinary calculi were
      included. Each calculus was measured independently by 11 readers. The mean value
      of their size estimations was used as validation data for each calculus. The
      segmentation algorithm consisted of interpolated zoom, binary thresholding and
      morphological operations. Ten examinations were used for algorithm optimisation
      and 40 for validation. Based on the optimisation results three segmentation
      method candidates were identified. RESULTS: Between the primary segmentation
      algorithm using cubic spline interpolation and the mean estimation by 11 readers,
      the bias was 0.0 mm, the standard deviation of the difference 0.26 mm and the
      Bland-Altman limits of agreement 0.0 +/- 0.5 mm. CONCLUSIONS: The validation
      showed good agreement between the suggested algorithm and the mean estimation by
      a large number of readers. The limit of agreement was narrower than the inter
      reader limit of agreement previously reported for the same data. KEY POINTS: The
      size of kidney stones is usually estimated manually by the radiologist. An
      algorithm for computer-aided size estimation is introduced. The variability
      between readers can be reduced. A reduced variability can give better information
      for treatment decisions.

PMID- 22160168
TI  - Flat panel CT following stapes prosthesis insertion: an experimental and clinical
      study.
AB  - OBJECTIVES: Anatomical information of the middle and inner ear is becoming
      increasingly important in post-operative evaluation especially after stapesplasty
      with unsuccessful improvement of the air-bone gap (ABG). So far computed
      tomography (CT) has been the first choice for detection of reasons for recurrent
      hearing loss. CT has the disadvantage of metal-induced artefacts after insertion
      of middle ear implants and of a relatively high irradiation dose. METHODS: Flat
      panel CT (fpCT) was performed in three temporal bone specimen after experimental
      insertion of different stapes prostheses, aiming to validate the accuracy of fpCT
      of the middle and inner ear. Additionally, 28 consecutive patients, supplied with
      different stapes prostheses underwent post-operative fpCT to compare the pre- and
      post-operative hearing results with the determined prosthesis position in the
      middle and inner ear. RESULTS: In all cases, fpCT showed a statistically
      significant correlation between hearing improvement and prosthesis position. This
      technique provided detailed post-operative information of the implant position in
      patients and temporal bone specimen. CONCLUSIONS: The new imaging technique of
      fpCT allows the immediate and almost artefact-free evaluation of surgical results
      following stapesplasty. Further benefits are a lower irradiation dose and higher
      isovolumetric resolution compared with standard CT. KEY POINTS: Flat panel
      computed tomography (fpCT) helps otosurgeons design precise stapes protheses.
      fpCT allows a prediction of the postoperative hearing outcome in patients. fpCT
      is an adequate imaging technique for immediate postoperative quality control.
      Postoperative management of patients with prosthesis-related complications is
      more appropriate.

PMID- 22160169
TI  - Waist-to-height ratio, waist circumference, and body mass index as indices of
      cardiometabolic risk among 36,642 Taiwanese adults.
AB  - PURPOSE: We aimed to investigate the association of body mass index (BMI), waist
      circumference (WC), and waist-to-height ratio (WHtR) with cardiometabolic risk.
      METHODS: In this cross-sectional study, 21,038 men and 15,604 women who
      participated in a health check-up were included. RESULTS: In both men and women,
      the area under the curve (AUC) of WHtR was significantly greater than that of BMI
      or WC in the prediction of diabetes, hypertension, high total cholesterol, high
      triglycerides, and low HDL-cholesterol (P < 0.05 for all). The AUC for WHtR in
      the prediction of metabolic syndrome (MS) was also highest in the women (P <
      0.05). After adjustment for potential confounders, the odds ratios and 95%
      confidence intervals for MS for each standard deviation increase in BMI, WHtR,
      and WC were 1.47 (1.46-1.49), 1.32 (1.31-1.33), and 1.19 (1.18-1.19),
      respectively. Finally, patients of either sex with a normal BMI or WC level, but
      with an elevated WHtR, had higher levels of various cardiometabolic risk factors
      in comparison with their normal BMI or WC, but low WHtR, counterparts (P < 0.05
      for all). CONCLUSION: Among Taiwanese adults, a WHtR greater than 0.5 is a
      simple, yet effective indicator of centralized obesity and associated
      cardiometabolic risk, even among individuals deemed 'healthy' according to BMI
      and WC.

PMID- 22160170
TI  - Ellagic acid coordinately attenuates Wnt/beta-catenin and NF-kappaB signaling
      pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis.
AB  - PURPOSE: Constitutive activation of the Wnt signaling pathway and its downstream
      effectors plays a key role in neoplastic transformation. The objective of this
      study was to investigate the effect of ellagic acid, a plant-derived polyphenol
      on Wnt/beta-catenin signaling and its downstream circuits- NF-kappaB and
      mitochondrial apoptosis in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced
      hamster buccal pouch (HBP) carcinogenesis model. METHODS: Hamsters were divided
      into six groups. The right buccal pouches of animals in groups 1-4 were painted
      with 0.5% DMBA three times a week for 14 weeks. Animals in groups 2-4 received in
      addition basal diet containing ellagic acid at a concentration of 0.1, 0.2, and
      0.4% in the diet. Group 5 animals were given 0.4% ellagic acid alone. Group 6
      animals served as control. The expression of the members of Wnt and NF-kappaB
      signaling and intrinsic apoptosis was evaluated by western blot analysis.
      RESULTS: Dietary supplementation of 0.4% ellagic acid suppressed the development
      of HBP carcinomas by preventing the constitutive activation of Wnt pathway
      through the downregulation of Fz, Dvl-2, GSK-3beta and nuclear translocation of
      beta-catenin. Abrogation of Wnt signaling by ellagic acid was also associated
      with inactivation of NF-kappaB and modulation of key components of the
      mitochondrial apoptotic network. CONCLUSIONS: Our findings suggest a functional
      crosstalk between Wnt and NF-kappaB signaling pathways in HBP carcinomas that is
      blocked by ellagic acid supplementation. Dietary ellagic acid that targets the
      Wnt/beta-catenin pathway as well as its downstream signaling mediators is a
      unique candidate for cancer chemoprevention.

PMID- 22160172
TI  - Prophylactic intraoperative powdered vancomycin and postoperative deep spinal
      wound infection: 1,512 consecutive surgical cases over a 6-year period.
AB  - PURPOSE: The purpose of this study is to evaluate the effect of intraoperative
      powdered vancomycin on the rates of postoperative deep spinal wound infection.
      The use of intraoperative powdered vancomycin as a prophylactic measure in an
      attempt to reduce the incidence of postoperative spinal wound infection has not
      been sufficiently evaluated in the existing literature. A retrospective review of
      a large clinical database was performed to determine the rates of deep wound
      infection associated with the use of intraoperative operative site powdered
      vancomycin. MATERIALS AND METHODS: During the period from 2005 to 2010, 1,512
      consecutive spinal surgery cases were performed by the same fellowship-trained
      spinal surgeon (RWM) at a level 1 trauma-university medical center. One gram of
      powdered vancomycin was placed in all surgical sites prior to wound closure.
      Eight hundred forty-nine cases were uninstrumented, 478 cases were instrumented
      posterior thoracic or lumbar, 12 were instrumented anterior thoracic or lumbar,
      126 were instrumented anterior cervical, and 47 were instrumented posterior
      cervical cases. Fifty-eight cases were combined anterior and posterior surgery
      and 87 were revision surgeries. A retrospective operative database and medical
      record review was performed to evaluate for evidence of postoperative deep wound
      infection. RESULTS: 15 of the 1,512 patients (0.99%) were identified as having
      evidence of postoperative deep wound infection. At least one pre-existing risk
      factor for deep infection was present in 8/15 pts (54%). Staphylococcus aureus
      and methicillin-resistant S. aureus (MRSA) were the most commonly identified
      organisms (11/15 cases). The rate of deep wound infection was 1.20% (8/663) for
      instrumented spinal surgeries, and 0.82% (7/849) for uninstrumented surgeries.
      Deep infection occurred in only 1.23% (4/324) of multilevel instrumented
      posterior spinal fusions, 1.37% (1/73) of open PLIF procedures, and 1.23% (1/81)
      of single-level instrumented posterior fusions. Deep infection was not observed
      in any patient who had uninstrumented spinal fusion (0/64). The deep infection
      rate for revision surgeries was 1.15% (1/87) and 0.55% (1/183) for trauma
      surgery. Increased rates of complications related to powdered vancomycin use were
      not identified in this series. Conclusion In this series of 1,512 consecutive
      spinal surgeries, the use of 1 g of powdered intraoperative vancomycin placed in
      the wound prior to wound closure appears to associated with a low rate deep
      spinal wound infection for both instrumented and uninstrumented cases. Rates of
      deep infection for instrumented fusion surgery, trauma, and revision surgery
      appear to be among the lowest reported in the existing literature. Further
      investigation of this prophylactic adjunctive measure is warranted.

PMID- 22160173
TI  - Percutaneous augmented instrumentation of unstable thoracolumbar burst fractures.
AB  - BACKGROUND: Internal fixation of unstable thoracolumbar spine fractures requires
      correction of the lacking anterior column support. This usually entails insertion
      of a vertebral body replacement strut through an anterior approach, or a long
      posterior construct spanning at least two vertebrae above and two vertebrae below
      the fracture. Posterior short-segment pedicle instrumentation (SSPI)--one
      vertebra above and below--is suitable for approximately 40% of fractures, but not
      for all. METHODS: A total of 52 patients with unstable thoracolumbar burst
      fractures meeting our inclusion criteria were instrumented using a novel
      approach, combining percutaneous SSPI, pedicle screw augmentation with polymethyl
      methacrylate (PMMA) and fractured vertebra kyphoplasty. We retrospectively
      reviewed patient and fracture data, operative results and 1 year radiographic
      follow-up postoperatively in 40 of the patients. We reviewed operative
      complications of all 52 patients. RESULTS: Most fractures were AO/Magerl type
      A3.1, A3.2 and A3.3. They were instrumented within 72 h and ambulated without
      additional external bracing. Operative time averaged 2 h and blood loss was less
      than 50 cc in most cases. Complications were mostly related to PMMA leakage. On
      average, 3.3 degrees  (0-13) of correction was lost after 3 months, but remained
      constant afterward. CONCLUSIONS: Percutaneous augmented short-segment pedicle
      instrumentation of unstable thoracolumbar fractures can be done with short
      operative times, minimal blood loss and a low complication rate. The
      radiographical results at 1 year are equal to anterior stabilization and are
      better than other posterior-only techniques.

PMID- 22160175
TI  - Identification of ERp29 as a biomarker for predicting nasopharyngeal carcinoma
      response to radiotherapy.
AB  - Radioresistance continues to be a major problem in the treatment of
      nasopharyngeal carcinoma (NPC). This study aimed to identify novel proteins
      associated with NPC radio-resistance. We used a mass spectrometry driven
      proteomic strategy to identify novel proteins associated with NPC radio
      resistance, and differential proteins were subsequently processed by bio
      informatic analysis. As a result, twelve proteins were identified with aberrant
      expression in radioresistant (RR) NPC tissues compare to radiosensitive (RS) NPC
      tissues. Among these proteins, ERp29, Mn-SOD, HSP27 and GST omega1 were found to
      be significantly up-regulated in RR NPC tissues, and ERp29 was selected for
      further validation. Immunohistochemistry analysis confirmed that ERp29 was
      overexpressed in RR NPC tissues compared with RS NPC tissues. To prove the role
      of ERp29 in the induction of NPC radioresistance, ERp29 was down-regulated in the
      ERp29 enriched NPC cells CNE-1 and 6-10B by specific shRNA. Radiosensitivity was
      measured using cell proliferation assay and clonogenic survival assay, and cell
      apoptosis was measured using flow cytometric analysis. We found that ERp29
      knockdown attenuated CNE-1 and 6-10B cell radioresistance and enhanced cell
      apoptosis. These results suggest that ERp29 associates with radioresistance in
      NPC, and ERp29 could be a potential biomarker for predicting NPC response to
      radiotherapy.

PMID- 22160176
TI  - Preclinical characterization of 18F-D-FPHCys, a new amino acid-based PET tracer.
AB  - PURPOSE: The imaging potential of a new (18)F-labelled methionine derivative, S
      (3-[(18)F]fluoropropyl)-D-homocysteine ((18)F-D-FPHCys), and its selectivity for
      amino acid transporter subtypes were investigated in vitro and by imaging of
      human tumour xenografts. METHODS: Expression of members of the system L (LAT
      isoforms 1-4 and 4F2hc) and ASCT (ASCT isoforms 1 and 2) amino acid transporter
      subclasses were assessed by quantitative real-time PCR in four human tumour
      models, including A431 squamous cell carcinoma, PC3 prostate cancer, and Colo 205
      and HT-29 colorectal cancer lines. The first investigations for the
      characterization of (18)F-D-FPHCys were in vitro uptake studies by comparing it
      with [1-(14)C]-L-methionine ((14)C-MET) and in vivo by PET imaging. In addition,
      the specific involvement of LAT1 transporters in (18)F-D-FPHCys accumulation was
      tested by silencing LAT1 mRNA transcription with siRNAs. To determine the
      proliferative activity in tumour xenografts ex vivo, Ki-67 staining was used as a
      biomarker. RESULTS: A431 cells showed the highest (18)F-D-FPHCys uptake in vitro
      and in vivo followed by Colo 205, PC3 and HT-29. A similar pattern of retention
      was observed with (14)C-MET. (18)F-D-FPHCys retention was strongly correlated
      with LAT1 expression both in vitro (R(2) = 0.85) and in vivo (R(2) = 0.99).
      Downregulation of LAT1 by siRNA inhibited (18)F-D-FPHCys uptake, demonstrating a
      clear dependence on this transporter for tumour uptake. Furthermore, (18)F-D
      FPHCys accumulation mirrored cellular proliferation. CONCLUSION: The favourable
      properties of (18)F-D-FPHCys make this tracer a promising imaging probe for
      detection of tumours as well as for the noninvasive evaluation and monitoring of
      tumour growth.

PMID- 22160177
TI  - Interaction of cartilage and ceramic matrix.
AB  - As subchondral bone is often affected during cartilage injuries, the aim of
      research is to generate osteochondral implants in vitro using tissue engineering
      techniques. These constructs consist of a cartilage layer grown on top of a bone
      phase. In clinical applications, phosphate ceramics have gained acceptance as
      bone substitute materials because of their great affinity to natural bone.
      Furthermore, the interaction between cartilage and the underlying bone equivalent
      is essential for the development and success of osteochondral implants. Here, the
      influence of a carrier containing hydroxyapatite on the quality of cartilage
      constructs generated in vitro is investigated. Attempts are made to explain the
      effects described, by considering chemical and physical properties of the
      biomaterial.

PMID- 22160178
TI  - Anatomical relationship between cranial surface landmarks and venous sinus in
      posterior cranial fossa using CT angiography.
AB  - PURPOSE: The purpose of this study was to determine the reliability of applying
      conventional anatomical landmarks to locate venous sinus in posterior fossa using
      subtraction computed tomography angiography (CTA) technique. METHODS: We
      retrospectively reconstructed transverse sinus (TS), sigmoid sinus (SS), and
      cranial imaging from 100 patients undergoing head CTA examination. Subtraction
      CTA data was merged with nonenhanced data and then cranium transparency was
      adjusted to 50% on three-dimensional volume rendering, indicating the anatomical
      relationship between surface landmarks of cranium and confluens sinuum, TS, and
      SS. RESULTS: CTA technique precisely displayed the anatomical relations between
      venous sinus in posterior fossa and cranial surface landmarks. The asterion was
      located directly over the transverse-sigmoid sinus junction (TSST) in 81% cases,
      inferior to TSST in 15%, and superior to TSST in 4%, mainly distributing on the
      TS side of TSST, namely the distal-end of TS. Superior nuchal line had complex
      relation with TS and the line drawn from the zygoma root to the inion (LZI), but
      failed to represent the location of TS and the trend of LZI. In proximal-end of
      TS, majority of LZI overlapped with TS line. However, most LZI was gradually
      positioned below TS line as TS moved outwards. Almost half of line drawn from the
      squamosal-parietomastoid suture junction to the inion and line drawn from the
      asterion to the inion shared the same trend with TS. CONCLUSION: Subtraction CTA
      merged into nonenhanced cranial bone with 50% skull transparency provides a
      feasible method to identify the anatomical relation between venous sinus and
      surface landmarks of cranium, which is significantly varied among individuals, so
      it is not accurate to determine venous sinus in posterior fossa merely using
      surface landmarks.

PMID- 22160179
TI  - Differential diagnosis of frontal lobe dilated perivascular spaces.

PMID- 22160181
TI  - Thoracic neoplasms at the Jena reference center for soft tissue tumors.
AB  - INTRODUCTION: The Jena Soft Tissue Tumor Reference Center is the major German
      pathology institute for consultation of malignant mesenchymal tumors. Here, we
      present the clinicopathological data on thoracic soft tissue tumors of a two-year
      period. METHODS: The tumors were analyzed according to their localization, type
      (soft tissue tumor, other tumor type, non-neoplastic lesion) and biological
      behavior. The frequency of the defined soft tissue tumor entities were considered
      after categorizing the cases according to the WHO Classification of Tumors.
      Gender and age were also assessed. RESULTS: In total, 1,071 cases of thoracic
      tumors were recorded within the 2 years. The majority were non-epithelial lesions
      (75.3%, n = 806/1,071), of which 68.1% (n = 549/806) were malignant or
      intermediate malignant. 107 non-epithelial lesions involved the lung and 37 the
      pleura. By far the most common lung and pleural tumors were undifferentiated
      sarcomas. In the lung, other frequent entities were solitary fibrous tumors,
      synovial sarcomas and leiomyosarcomas. We also recorded 13 non-epithelial tumors
      of the heart and 66 tumors of the breast with angiosarcomas being the most
      frequent subtype. There was a female predominance for vascular neoplasms, while
      men prevailed for adipocytic tumors. CONCLUSIONS: Our study provides information
      about the frequency, distribution, age and gender of patients with thoracic soft
      tissue tumors including several rare entities. Thus, it may help in the
      differential diagnosis of these neoplasms. In addition, we present a model
      highlighting the potential progression of lung carcinoma to undifferentiated
      sarcoma via the process of epithelial-mesenchymal transition.

PMID- 22160182
TI  - Inhibition of Aurora kinases enhances chemosensitivity to temozolomide and causes
      radiosensitization in glioblastoma cells.
AB  - BACKGROUND: Glioblastoma remains one of the most devastating human malignancies,
      and despite therapeutic advances, there are no drugs that significantly improve
      the patient survival. Altered expression of the Aurora kinases was found in
      different malignancies, and their inhibition has been studied in cancer therapy.
      In this study, we analyzed the expression of Aurora A and Aurora B in
      glioblastoma samples and also analyzed whether the effects of Aurora kinase
      inhibition were associated with temozolomide or not on cell lines and primary
      cultures of glioblastoma. MATERIALS AND METHODS: RT-PCR assays were used to
      determine the mRNA expression in glioblastoma tumor samples and in the cell
      lines. Cell proliferation was measured by XTT assay, and apoptosis was determined
      by flow cytometry. Drug combination analyses were made based in Chou-Talalay
      method. Gamma radiation for clonogenic survival used the doses of 2, 4 and 6 Gy.
      Changes in Aurora B level were assessed by Western blot analysis. RESULTS: Aurora
      A and B were expressed in glioblastoma samples as well as in the glioblastoma
      cell lines (n = 6). Moreover, ZM447439, a selective Aurora kinase inhibitor,
      decreased the proliferation separately and synergistically with temozolomide in
      primary cultures and cell lines of glioblastoma. ZM also enhanced the effects of
      radiation on the two cell lines studied (U343 and U251), mainly when associated
      with TMZ in U343 cells. Treatment with ZM induced apoptotic cell death and
      diminished Aurora B protein level. CONCLUSIONS: These data suggest that Aurora
      kinase inhibition may be a target for glioblastoma treatment and could be used as
      adjuvant to chemo- and radiotherapy.

PMID- 22160183
TI  - Dietary herring improves plasma lipid profiles and reduces atherosclerosis in
      obese low-density lipoprotein receptor-deficient mice.
AB  - Diet is a significant modifiable risk factor for cardiovascular disease and high
      fish intake has been associated with vascular health in population studies.
      However, intervention studies have been inconclusive. In this study, male low
      density lipoprotein receptor-deficient mice were given 16-week high fat/high
      sucrose diets, supplemented with either minced herring fillets or minced beef.
      The diets were matched in total fat and cholesterol content; taurine content and
      fatty acid composition was analysed. Body weights were recorded throughout the
      study; plasma lipids were analysed at week 8 and 16. Body composition and
      adipocyte size were evaluated at study end. Atherosclerosis was evaluated at week
      12 (ultrasound) and at termination (en face histology). Herring-fed mice had a
      higher proportion of long-chain n-3 polyunsaturated fatty acids in the hepatic
      triacylglycerides (TAG) and phospholipid fractions. The herring-fed mice had
      increased body weight (P=0.007), and reduced epididymal adipocyte size (P=0.009),
      despite similar food intake and body composition as the beef-fed mice. The
      herring-fed mice had lower plasma TAG and very-low-density lipoprotein (VLDL)
      cholesterol concentrations throughout the study (TAG; P=0.0012 and 0.004, VLDL
      cholesterol; P=0.006 and 0.041, week 8 and 16, respectively). At week 16, the
      herring-fed had higher plasma concentrations of HDL-cholesterol (P=0.004) and
      less atherosclerotic lesions in the aortic arch (P=0.007) compared with the beef
      fed mice. In conclusion, dietary herring in comparison to beef markedly improved
      vascular health in this mouse model, suggesting that herring provides an added
      value beyond its content of macronutrients.

PMID- 22160184
TI  - New similarity search based glioma grading.
AB  - INTRODUCTION: MR-based differentiation between low- and high-grade gliomas is
      predominately based on contrast-enhanced T1-weighted images (CE-T1w). However,
      functional MR sequences as perfusion- and diffusion-weighted sequences can
      provide additional information on tumor grade. Here, we tested the potential of a
      recently developed similarity search based method that integrates information of
      CE-T1w and perfusion maps for non-invasive MR-based glioma grading. METHODS: We
      prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III
      gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and
      perfusion sequences was performed. Cerebral blood volume, cerebral blood flow,
      and mean transit time maps as well as CE-T1w images were used as input for the
      similarity search. Data sets were preprocessed and converted to four-dimensional
      Gaussian Mixture Models that considered correlations between the different MR
      sequences. For each patient, a so-called tumor feature vector (= probability
      based classifier) was defined and used for grading. Biopsy was used as gold
      standard, and similarity based grading was compared to grading solely based on CE
      T1w. RESULTS: Accuracy, sensitivity, and specificity of pure CE-T1w based glioma
      grading were 64.9%, 78.6%, and 56.5%, respectively. Similarity search based tumor
      grading allowed differentiation between low-grade (I or II) and high-grade (III)
      gliomas with an accuracy, sensitivity, and specificity of 83.8%, 78.6%, and
      87.0%. CONCLUSION: Our findings indicate that integration of perfusion parameters
      and CE-T1w information in a semi-automatic similarity search based analysis
      improves the potential of MR-based glioma grading compared to CE-T1w data alone.

PMID- 22160180
TI  - Measurement of human energy expenditure, with particular reference to field
      studies: an historical perspective.
AB  - Over the years, techniques for the study of human movement have ranged in
      complexity and precision from direct observation of the subject through activity
      diaries, questionnaires, and recordings of body movement, to the measurement of
      physiological responses, studies of metabolism and indirect and direct
      calorimetry. This article reviews developments in each of these domains.
      Particular reference is made to their impact upon the continuing search for valid
      field estimates of activity patterns and energy expenditures, as required by the
      applied physiologist, ergonomist, sports scientist, nutritionist and
      epidemiologist. Early observers sought to improve productivity in demanding
      employment. Direct observation and filming of workers were supplemented by
      monitoring of heart rates, ventilation and oxygen consumption. Such methods still
      find application in ergonomics and sport, but many investigators are now
      interested in relationships between habitual physical activity and chronic
      disease. Even sophisticated questionnaires still do not provide valid information
      on the absolute energy expenditures associated with good health. Emphasis has
      thus shifted to use of sophisticated pedometer/accelerometers, sometimes
      combining their output with GPS and other data. Some modern
      pedometer/accelerometers perform well in the laboratory, but show substantial
      systematic errors relative to laboratory reference criteria such as the
      metabolism of doubly labeled water when assessing the varied activities of daily
      life. The challenge remains to develop activity monitors that are sufficiently
      inexpensive for field use, yet meet required accuracy standards. Possibly,
      measurements of oxygen consumption by portable respirometers may soon satisfy
      part of this need, although a need for valid longer term monitoring will remain.

PMID- 22160186
TI  - Development of a protocol for supercritical carbon dioxide extraction of
      ubiquinone-10 from dried biomass of Pseudomonas diminuta.
AB  - Ubiquinone (Coenzyme Q10, CoQ10), a yellow-to-orange-colored lipophilic substance
      having nutraceutical value, was extracted from dried biomass of Pseudomonas
      diminuta using supercritical carbon dioxide (SC-CO(2)). The effect of different
      operational parameters (temperature, pressure, and extraction time) and addition
      of co-solvent on SC-CO(2) extraction of CoQ10 was studied in detail. The
      solubility parameter of CoQ10, CO(2), and CO(2) with ethanol and methanol as co
      solvents was calculated and validated with experimental results. Theoretically,
      ethanol and methanol had significant effect as co-solvent, and the difference
      between the two was only marginal. A maximum recovery of 22.33% was obtained
      using pure SC-CO(2) at 40  degrees C, 150 bar, and run time of 60 min. Ethanol as
      co-solvent at 3 mL/g of dried biomass at 40  degrees C and 150 bar increased the
      recovery from 22.33 to 68.57%. Further optimization of the extraction conditions
      by Box-Behnken design effectively increased the recovery to 96.2%. The optimized
      conditions were a temperature of 38  degrees C, pressure of 215 bar, and run time
      of 58 min.

PMID- 22160185
TI  - Airway IFN-gamma production during RSV bronchiolitis is associated with
      eosinophilic inflammation.
AB  - STUDY OBJECTIVE: This study was designed to investigate the possible role of IFN
      gamma in eosinophil degranulation that occurs during respiratory syncytial virus
      (RSV) bronchiolitis. METHODS: Sixty-seven infants, 2-24 months old and
      hospitalized with their first episode of acute RSV bronchiolitis, were selected
      for this study. Eosinophil-active cytokine and chemokine profiles in nasal lavage
      supernatants taken within the first 48 h of admission were determined by a
      multiplex bead array system (Luminex). Comparisons were made with control
      (Control group) subjects (n = 20). RESULTS: Nasal IFN-gamma levels were
      significantly higher (P < 0.0001) in RSV bronchiolitis (median = 4.4 pg/ml)
      infants compared to controls (0.0 pg/ml). IFN-gamma levels correlated
      significantly with the levels of nasal eotaxin (r = 0.566, P < 0.0001), RANTES (r
      = 0.627, P < 0.0001), GM-CSF (r = 0.849, P < 0.0001), and EDN (r = 0.693, P <
      0.001). Nasal interleukin (IL)-4, IL-5, and IL-13 were below sensitivity levels
      in most RSV bronchiolitis and control subjects. CONCLUSION: These results suggest
      that IFN-gamma may play an important role in eosinophilic inflammation in RSV
      bronchiolitis.

PMID- 22160187
TI  - Suppression of microRNA-96 expression inhibits the invasion of hepatocellular
      carcinoma cells.
AB  - MicroRNA-96 (miR-96) expression is dysregulated in certain types of cancers.
      However, the role of miR-96 in hepatocellular carcinoma (HCC) invasion and
      metastasis remains elusive. miR-96 expression was investigated in a number of HCC
      cell lines by quantitative reverse transcription-polymerase chain reaction (RT
      PCR). Cell invasive ability of metastatic HCCLM6 cells transfected with anti-miR
      96 oligonucleotides or miR-96 mimic was determined by Matrigel invasion assay in
      vitro. In addition, metastasis-associated protein, osteopontin, was evaluated by
      Western blotting. miR-96 expression was significantly increased in highly
      metastatic HCCLM6 cells. Decreasing miR-96 expression with anti-miR-96
      oligonucleotides led to reduced migration and invasion of HCCLM6 cells in vitro.
      In particular, down-regulation of miR-96 decreased osteopontin expression in
      HCCLM6 cells. Suppression of miR-96 expression inhibits the invasion of HCC
      cells, suggesting that miR-96 may be a therapeutic target for inhibiting HCC
      invasion and metastasis.

PMID- 22160188
TI  - Plant cell wall secretion and lipid traffic at membrane contact sites of the cell
      cortex.
AB  - Plant cell wall secretion is the result of dynamic vesicle fusion events at the
      plasma membrane. The importance of the lipid bilayer environment of the plasma
      membrane and its interactions with the endomembrane system through vesicle
      traffic are well recognized. Recent advances in yeast molecular biology and
      biochemistry lead us to re-examine the hypothesis that non-vesicular traffic of
      lipids through close contact sites of the plasma membrane and endoplasmic
      reticulum could also be important in plant cell wall biosynthesis. Non-vesicular
      traffic is the extraction and transfer of individual lipid molecules from a donor
      bilayer to a target bilayer, usually with the assistance of lipid transfer
      proteins.

PMID- 22160189
TI  - Expression characterization of genes for CMS-C in maize.
AB  - Cytoplasmic male sterility (CMS)-C is one of the most attractive sources of male
      sterility in the production of hybrid maize. However, the abortion mechanism of
      CMS-C is currently unknown. The major aim of this work was to characterize the
      expression of genes and proteins during pollen abortion. The materials assayed
      included CMS-C line C48-2, its maintainer line N48-2, and fertile F(1) (C48-2 *
      18 white). A total of 20 unique genes and 25 proteins were identified by
      suppression subtractive hybridization and 2-D electrophoresis, respectively. Most
      of the genes and proteins identified are closely related to energy metabolism,
      stress responses, molecular chaperones, and cell death, which are generally
      considered to be essential to pollen development. Based on the function of these
      identified genes and proteins, reactive oxygen species in isolated mitochondria
      and DNA fragments were analyzed. The results from this study indicate that the
      oxidative stress which was associated with the specific expression patterns of
      some genes may be the physiological cause for the abortion of premature
      microspores in the maize CMS-C line.

PMID- 22160190
TI  - Mitotic inheritance of endoplasmic reticulum in the primitive red alga
      Cyanidioschyzon merolae.
AB  - Endoplasmic reticulum (ER) is a major site for secretory protein folding and
      lipid synthesis. Since ER cannot be synthesized de novo, it must be inherited
      during the cell cycle. Studying ER inheritance can however be difficult because
      the ER of typical plant and animal cells is morphologically complex. Therefore,
      our study used Cyanidioschyzon merolae, a species that has a simple ER structure,
      to investigate the inheritance of this organelle. Using immunofluorescence
      microscopy, we demonstrated that C. merolae contains a nuclear ER (nuclear
      envelope) and a small amount of peripheral ER extending from the nuclear ER.
      During mitosis, the nuclear ER became dumbbell-shaped and underwent division.
      Peripheral ER formed ring-like structures during the G1 and S phases, and
      extended toward the mitochondria and cell division planes during the M phase.
      These observations indicated that C. merolae undergoes closed mitosis, whereby
      the nuclear ER does not diffuse, and the peripheral ER contains cell cycle
      specific structures.

PMID- 22160191
TI  - Silk and silkworm pupa peptides suppress adipogenesis in preadipocytes and fat
      accumulation in rats fed a high-fat diet.
AB  - PURPOSE: The objective was to confirm the anti-obesity activity of a silk peptide
      (SP) and a silkworm pupa peptide (SPP) in rats fed a high-fat diet (HFD) and to
      elucidate their action mechanism(s) in a preadipocyte culture system. METHODS: In
      an in vitro mechanistic study, the differentiation and maturation of 3T3-L1
      preadipocytes were stimulated with insulin (5 MUg/mL), and effects of SP and SPP
      on the adipogenesis of mature adipocytes were assessed. In an in vivo anti
      obesity study, male C57BL/6 mice were fed an HFD containing SP or SPP (0.3, 1.0,
      or 3.0%) for 8 weeks, and blood and tissue parameters of obesity were analyzed.
      RESULTS: Hormonal stimulation of preadipocytes led to a 50-70% increase in
      adipogenesis. Polymerase chain reaction and Western blot analyses revealed
      increases in adipogenesis-specific genes (leptin and Acrp30) and proteins
      (peroxisome proliferator-activated receptor-gamma and Acrp30). The hormone
      induced adipogenesis and activated gene expression was substantially inhibited by
      treatment with SP and SPP (1-50 MUg/mL). The HFD markedly increased body weight
      gain by increasing the weight of epididymal and mesenteric fat. Body and fat
      weights were significantly reduced by SP and SPP, in which decreases in the area
      of abdominal adipose tissue and the size of epididymal adipocytes were confirmed
      by magnetic resonance imaging and microscopic examination, respectively. Long
      term HFD caused hepatic lipid accumulation and increased blood triglycerides and
      cholesterol, in addition to their regulatory factors Acrp30 and leptin. However,
      SP and SPP recovered the concentrations of Acrp30 and leptin, and attenuated
      steatosis. CONCLUSIONS: SP and SPP inhibit the differentiation of preadipocytes
      and adipogenesis by modulating signal transduction pathways and improve HFD
      induced obesity by reducing lipid accumulation and the size of adipocytes.

PMID- 22160192
TI  - [Awake fiberoptic intubation].
AB  - Airway management is a core task for anesthesiologists. Deficiencies in training
      or equipment as well as fateful complications in this field are responsible for a
      significant proportion of anesthesia-associated morbidity and mortality. Nowadays
      there are a variety of advanced technical aids on the market to overcome the
      difficult airway. Nevertheless, the "cannot intubate cannot ventilate scenario"
      still occurs and regularly results in poor outcome, such as permanent
      neurological deficits or even death. Therefore, awake fiberoptic intubation
      remains the gold standard in the expected difficult airway because when applied
      correctly this technique never leads to a point where a patient's respiration is
      compromised as a result of medical measures before a secure airway has been
      established.

PMID- 22160193
TI  - Flavanones inhibit the clonogenicity of HCT116 cololectal cancer cells.
AB  - Naringenin has been shown to display various biological effects such as
      antioxidant, anticancer, anti-inflammatory, and antiviral activities. Taxifolin
      inhibits the production of lipopolysaccharide-induced prostaglandin E, and fustin
      suppresses the activity of acetylcholinesterase. They all belong to flavanone
      which is a class of flavonoids with a C6-C3-C6 skeleton. Since the anticancer
      activities of flavanone derivatives have rarely been reported, we examined the
      effects of 26 flavanone derivatives on HCT116 colorectal cancer cells. Our
      results suggest that flavanone derivatives control the expression of cell cycle
      regulatory proteins, which blocks G1 cell cycle progression and inhibits the
      clonogenicity of HCT116 cells. In addition, in order to design flavanone
      derivatives that show better anticancer activity, structure-activity
      relationships were examined.

PMID- 22160194
TI  - Diffusion tensor imaging applications in multiple sclerosis patients using 3T
      magnetic resonance: a preliminary study.
AB  - OBJECTIVES: This study evaluated patients with multiple sclerosis using diffusion
      tensor imaging (DTI) to obtain fractional anisotropy (FA) and mean diffusivity
      (MD) values. METHODS: We investigated the possible statistically significant
      variation of MD and FA in different MS patients, compared simultaneously, putting
      in comparison their normal appearing white matter (NAWM) and white matter
      affected by disease (plaques), both during activity and in remission, with normal
      white matter (NWM) of control subjects. RESULTS: Statistical analysis using
      Levene's test for comparison of variances revealed significant (P < 0.05)
      differences between FA values of the NWM of the controls and those of NAWM and
      active or inactive lesions, of the patients in the study. However, the
      differences between MD values of the NWM of the controls and those of NAWM and
      active or inactive lesions of the patients in the study were judged not
      significant (P > 0.05). CONCLUSION: Imaging of MS using MRI techniques is
      constantly searching for reproducible quantitative parameter. This study shows
      how these parameters can be identified in the MD and FA values, and thus suggests
      the implementation of MRI routine protocols for diagnosing MS with the DTI
      analysis, since it can provide valuable information otherwise unobtainable. KEY
      POINTS: Magnetic resonance imaging is widely performed in multiple sclerosis (MS)
      patients Diffusion tensor imaging (DTI) can be implemented using a 3T magnet DTI
      provides quantitative parameters as mean diffusivity (MD) and fractional
      anisotropy (FA) MD and, especially, FA can help evaluate the lesion load in MS
      patients and also assess variation in normal appearing white matter (NAWM) in MS.

PMID- 22160195
TI  - Suggested pathway to assess radiation safety of 11C-labeled PET tracers for first
      in-human studies.

PMID- 22160197
TI  - ST-segment depression during vasodilator stress is of minor clinical importance
      in women with normal myocardial perfusion imaging and low or intermediate risk of
      coronary artery disease.
AB  - PURPOSE: The prognostic value of electrocardiographic (ECG) ST-segment depression
      during vasodilator stress testing in patients with normal myocardial perfusion
      scintigraphy (MPS) is based on retrospective studies with controversial results.
      Moreover, the true incidence of obstructive coronary artery disease (CAD) in
      these patients is unknown. METHODS: During a 33-month period, all consecutive
      patients referred for MPS were prospectively evaluated for interpretable ST
      segment depression >= 1 mm during vasodilator stress testing. Of 1,687 patients
      with normal MPS and without known CAD, 109 (100 women) aged 65.2 +/- 9.2 years
      demonstrated ST-segment shifts and formed the ECG-positive group. The pretest
      probability of CAD was low in 56%, intermediate in 39% and high in 5%. They were
      advised to proceed to coronary angiography. An equal number of patients with
      normal MPS and no ECG abnormalities matched for CAD predisposing factors
      comprised the control group. Follow-up of both groups was accomplished through a
      telephone interview. RESULTS: Fifty-two patients from the ECG-positive group
      (48%) consented to coronary angiography. Six (11.5%) had obstructive CAD (>=50%
      lumen stenosis), one with left main artery disease, while three required
      revascularization. Follow-up was complete in 99 ECG-positive patients for a
      period of 20.6 +/- 8.9 months. One hard event (non-fatal myocardial infarction)
      and one soft event (revascularization) were observed. No event was recorded in
      the control group. CONCLUSION: In patients with low-intermediate risk of CAD,
      "ischaemic" ECG changes during vasodilator stress combined with normal MPS are
      encountered mostly in women and are associated with a low prevalence of
      significant CAD and a low cardiac event rate.

PMID- 22160199
TI  - Technical feasibility vs. clinical utility: a question of "can we?" vs. "should
      we?".

PMID- 22160198
TI  - Prognostic value of sentinel lymph node biopsy in 121 low-risk melanomas (tumour
      thickness <1.00 mm) on the basis of a long-term follow-up.
AB  - PURPOSE: Sentinel lymph node biopsy (SLNB) is a widely accepted procedure to
      accurately stage melanomas with a thickness >=1 mm. The value of SLNB in thin
      melanomas is still controversial, especially because long-term observations of
      these patients are rare. The purpose of the current study was to identify the
      positive sentinel lymph node (SLN) ratio in low-risk patients with cutaneous
      melanoma (CM) of thickness less than 1 mm and its possible prognostic value,
      focusing on long-term follow-up data. METHODS: In a retrospective single-centre
      study performed at the Department of Dermatology and Allergy, University of Bonn,
      121 patients who had received SLNB were identified out of 621 patients with a
      diagnosis of CM of <1.00 mm thickness presenting between September 2000 and
      February 2009 (mean follow-up time, 50.9 months). RESULTS: Of the 121 patients, 5
      (4.1%) had a positive SLN. All positive SLNs were found in patients with a tumour
      thickness between 0.90 mm and 1.00 mm. There were no significant differences in
      the presence of positive SLNs according to Clark level and ulceration status
      (Clark levels II and III and no ulceration vs. Clark levels IV and V or
      ulceration), regression, gender or age. Disease-free survival was 100% in the SLN
      positive patients. On the other hand, five SLN-negative patients (4.1%) developed
      disease progression. One of these five progressive patients showed recurrence in
      the former negative SLN basin (16.7% false-negative rate). CONCLUSION: A positive
      SLN in thin melanomas is uncommon with a prevalence of 4.1% in our study
      population. We could not identify reliable clinicopathological risk factors which
      could predict results of SLNB in thin melanomas. Based on our results, SLNB may
      be considered in patients with a melanoma of thickness in the range 0.90-0.99 mm,
      because all SLN-positive patients belonged to this subgroup.

PMID- 22160200
TI  - Discontinuation of prolonged infusions of dexmedetomidine in critically ill
      children with heart disease.
AB  - PURPOSE: To describe changes in hemodynamic variables, sedation, and pain score
      after discontinuation of prolonged infusions of dexmedetomidine in a pediatric
      population of critically ill cardiac patients. METHODS: Retrospective case series
      of patients who received continuous infusions of dexmedetomidine for longer than
      3 days in a pediatric cardiac intensive care unit from 2008 to 2010. RESULTS:
      Sixty-two patients, age 5.2 months (range 0.3 months-17 years) and weight 5.1 kg
      (range 2.2-84 kg), were included. Thirty-nine patients (63%) were younger than 1
      year of age. Median duration of dexmedetomidine infusion was 5.8 days (range 4-26
      days) and median infusion dose was 0.71 MUg/kg/h (range 0.2-2.1 MUg/kg/h). Median
      weaning time and dose at discontinuation were 43 h (range 0-189 h) and 0.2
      MUg/kg/h (range 0.1-1.3 MUg/kg/h). Tachycardia, transient hypertension and
      agitation were observed in 27, 35 and 27% of patients. Episodes of tachycardia
      were more frequent in children older than 1 year of age (61 vs. 8%, p < 0.001),
      patients who received dexmedetomidine for 4 days when compared to those who
      received 5 days or longer (48 vs. 17%, p = 0.011), and patients whose infusion
      was discontinued abruptly (42 vs. 14%, p = 0.045). Tachyarrhythmias were seen in
      nine patients (15%) after discontinuation of the dexmedetomidine infusion.
      Adequate sedation and analgesia scores at the moment of infusion discontinuation
      were seen in 90 and 88% of patients, respectively. CONCLUSIONS: Our study
      suggests that tachycardia, transient hypertension, and agitation are frequently
      observed in pediatric cardiac intensive care unit patients after discontinuing
      prolonged dexmedetomidine infusions.

PMID- 22160202
TI  - Forensic analysis of Salvia divinorum using multivariate statistical procedures.
      Part II: association of adulterated samples to S. divinorum.
AB  - Salvia divinorum is a plant material that is of forensic interest due to the
      hallucinogenic nature of the active ingredient, salvinorin A. In this study, S.
      divinorum was extracted and spiked onto four different plant materials (S.
      divinorum, Salvia officinalis, Cannabis sativa, and Nicotiana tabacum) to
      simulate an adulterated sample that might be encountered in a forensic
      laboratory. The adulterated samples were extracted and analyzed by gas
      chromatography-mass spectrometry, and the resulting total ion chromatograms were
      subjected to a series of pretreatment procedures that were used to minimize non
      chemical sources of variance in the data set. The data were then analyzed using
      principal components analysis (PCA) to investigate association of the adulterated
      extracts to unadulterated S. divinorum. While association was possible based on
      visual assessment of the PCA scores plot, additional procedures including
      Euclidean distance measurement, hierarchical cluster analysis, Student's t tests,
      Wilcoxon rank-sum tests, and Pearson product moment correlation were also applied
      to the PCA scores to provide a statistical evaluation of the association
      observed. The advantages and limitations of each statistical procedure in a
      forensic context were compared and are presented herein.

PMID- 22160201
TI  - Xenon offers stable haemodynamics independent of induced hypothermia after
      hypoxia-ischaemia in newborn pigs.
AB  - PURPOSE: To assess the effect of 18 hour (h) 50% xenon (Xe) inhalation at
      normothermia (NT, 38.5 degrees C) or hypothermia (HT, 33.5 degrees C) on mean
      arterial blood pressure (MABP), inotropic support and heart rate (HR) following
      an induced perinatal global hypoxic-ischaemic insult (HI) in newborn pigs.
      METHODS: Newborn pigs ventilated under inhalational anaesthesia, following a 45
      min HI (inhaled oxygen fraction reduced until amplitude integrated
      electroencephalogram was less than 7 MUV), were randomised to three Xe (n = 45)
      (50% Xe 18 h with NT, HT 12 h or HT 24 h) or three non-Xe groups (n = 53) (0% Xe
      with NT, HT 12 h or HT 24 h) under otherwise identical conditions. We measured
      MABP and HR every minute. Hypotension (MABP <40 mmHg) was treated sequentially
      with 2 * 10 mL/kg saline, dopamine, norepinephrine and hydrocortisone if
      required. RESULTS: Xe maintained higher MABP during HT (5.1 mmHg, 95% CI 2.34,
      7.89), rewarming (10.1 mmHg, 95% CI 6.26, 13.95) and after cessation (4.1 mmHg,
      95% CI 0.37, 7.84) independent of HT, inotropic support and acidosis. Xe reduced
      the duration of inotropic support by 12.6 h (95% CI 5.5, 19.73). Inotropic
      support decreased the HR reduction induced by HT from 9 to 5 bpm/ degrees C
      during cooling and from 10-7 to 4-3 bpm/ degrees C during rewarming. There was no
      interaction between Xe, HT, inotropic support and acidosis. Xe during HT cleared
      lactate faster; 3 h post-HI median (IQR) values of (Xe HT) 2.8 mmol/L (0.9, 3.1)
      vs. (HT) 5.9 mmol/L (2.5, 7.9), p = 0.0004. CONCLUSION: Xe maintained stable
      blood pressure, thereby reducing the inotropic support requirements during and
      after administration independently of induced HT-current neonatal encephalopathy
      treatment. Xe may offer haemodynamic benefits in clinical neuroprotection
      studies.

PMID- 22160203
TI  - A high-resolution phosphorus-31 nuclear magnetic resonance (NMR) spectroscopic
      method for the non-phosphorus markers of chemical warfare agents.
AB  - A high-resolution phosphorus-31 nuclear magnetic resonance (NMR) spectroscopic
      method has been developed for detection, identification and quantification of non
      phosphorus markers of toxic nerve agents (soman and V-class), vesicants (HD, HN
      2, HN-3), and incapacitating agent (Bz). These analytes were converted to
      phosphorus-containing derivatives via phosphitylation reaction of their hydroxyl
      and sulfhydryl functions (using 2-chloro-4,4,5,5-tetramethyl-1,3,2
      dioxaphospholane). This was followed by (31)P{(1)H} and (31)P NMR analysis of
      these derivatives. The chemical shifts (delta) and coupling constants ((3)J(P-H))
      of derivatives were used for their specific detection and identification. The
      method allowed clear distinction between the alcohols and thiols. The lower
      limits of detection of these analytes were found to be between 12 and 28 MUg
      obtained from 128 transients of (31)P{(1)H} quantitative NMR experiments. Utility
      of the method was ensured by the detection and identification of triethanolamine
      present (at an original concentration of 5 MUg/mL) in an aqueous sample from 28th
      OPCW Official Proficiency Tests.

PMID- 22160204
TI  - Evaluation of a novel ELISA for serotonin: urinary serotonin as a potential
      biomarker for depression.
AB  - Depression is a common disorder with physical and psychological manifestations
      often associated with low serotonin. Since noninvasive diagnostic tools for
      depression are sparse, we evaluated the clinical utility of a novel ELISA for the
      measurement of serotonin in urine from depressed subjects and from subjects under
      antidepressant therapy. We developed a competitive ELISA for direct measurement
      of serotonin in derivatized urine samples. Assay performance was evaluated and
      applied to clinical samples. The analytical range of the assay was from 6.7 to
      425 MUg serotonin/g creatinine (Cr). The limit of quantification was 4.7 MUg/g
      Cr. The average recovery for spiked urine samples was 104.4%. Average intra-assay
      variation was 4.4%, and inter-assay variation was <20%. The serotonin analysis
      was very specific. No significant interferences were observed for 44 structurally
      and nonstructurally related urinary substances. Very good correlation was
      observed between urinary serotonin levels measured by ELISA and liquid
      chromatography tandem mass spectrometry (LC-MS/MS; ELISA = 1.16 * LC-MS/MS -
      53.8; r = 0.965; mean % bias = 11%; n = 18). Serotonin was stable in acidified
      urine for 30 days at room temperature and at -20  degrees C. The established
      reference range for serotonin was 54-366 MUg/g Cr (n = 64). Serotonin levels
      detected in depressed patients (87.53 +/- 4.89 MUg/g Cr; n = 60) were
      significantly lower (p < 0.001) than in nondepressed subjects (153.38 +/- 7.99
      MUg/g Cr). Urinary excretion of serotonin in depressed individuals significantly
      increased after antidepressant treatment by 5-hydroxy-tryptophane and/or
      selective serotonin re-uptake inhibitor (p < 0.01). The present ELISA provides a
      convenient and robust method for monitoring urinary serotonin. It is suitable to
      monitor serotonin imbalances and may be particularly helpful in evaluating
      antidepressant therapies.

PMID- 22160205
TI  - Simultaneous online SPE-LC-MS/MS quantification of six widely used synthetic
      progestins in human plasma.
AB  - Co-administration of synthetic progestin containing hormonal contraceptives (HCs)
      and antiepileptic drugs (AEDs) is a common clinical situation which needs
      specific considerations due to drug interactions. Several studies have
      demonstrated that lamotrigine plasma levels are significantly decreased during co
      medication with HCs, and that this interaction is associated with increased
      seizure frequency in most of the cases. Additionally, an increase in
      contraceptive failure and unintended pregnancy could be observed during co
      medication. Hence, monitoring of progestin plasma levels in patients with AED co
      medication is of interest. A rapid and reliable online solid-phase extraction
      high performance liquid chromatography-tandem mass spectrometry (online SPE-LC
      MS/MS) method using gradient elution in the LC domain was established and
      validated for the simultaneous quantitative determination of gestodene,
      dienogest, drospirenone, etonogestrel, cyproterone acetate, and levonorgestrel in
      human plasma. The online SPE-LC-MS/MS method covered a quantification
      concentration range of 5-100 ng/ml for dienogest, 1-100 ng/ml for etonogestrel
      and 2-100 ng/ml for all other analytes. Stable isotope-labeled internal standards
      were used for analyte quantification based on selected reaction monitoring
      experiments. Inter- and intra-assay precision and accuracy were determined from
      quality control (QC) samples at the lower limits of quantification and at low,
      medium, and high concentration levels within the calibration range. Inter-assay
      reproducibility at the QC levels was better than 10% (relative standard
      deviation, RSD), accuracy at these levels ranged from -3.7% to 11.3%. Total
      extraction efficiency, tested at three concentrations, ranged from 92.5% to
      106.4%. Matrix interferences were excluded by post-column infusion experiments.
      To prove the applicability of the assay in clinical cohorts, a sample set (n =
      298) stemming from study patients under AED/oral HC co-medication was screened
      for progestin plasma levels. This method has to be considered a research-use-only
      assay and must not be used for diagnostic or therapeutic purposes, since it did
      not undergo formal performance evaluation in the sense of the IVD directive
      (98/79/EG) of the European Community.

PMID- 22160206
TI  - Specific peptides as alternative to antibody ligands for biomagnetic separation
      of Clostridium tyrobutyricum spores.
AB  - Nowadays, the reference method for the detection of Clostridium tyrobutyricum in
      milk is the most-probable-number method, a very time-consuming and non-specific
      method. In this work, the suitability of the use of superparamagnetic beads
      coated with specific antibodies and peptides for bioseparation and concentration
      of spores of C. tyrobutyricum has been assessed. Peptide or antibody
      functionalized nanoparticles were able to specifically bind C. tyrobutyricum
      spores and concentrate them up to detectable levels. Moreover, several factors,
      such as particle size (200 nm and 1 MUm), particle derivatization (aminated and
      carboxylated beads), coating method, and type of ligand have been studied in
      order to establish the most appropriate conditions for spore separation. Results
      show that concentration of spore is favored by a smaller bead size due to the
      wider surface of interaction in relation to particle volume. Antibody
      orientation, related to the binding method, is also critical in spore recovery.
      However, specific peptides seem to be a better ligand than antibodies, not only
      due to the higher recovery ratio of spores obtained but also due to the prolonged
      stability over time, allowing an optimal recovery of spores up to 3 weeks after
      bead coating. These results demonstrate that specific peptides bound to magnetic
      nanoparticles can be used instead of traditional antibodies to specifically bind
      C. tyrobutyricum spores being a potential basis for a rapid method to detect this
      bacterial target.

PMID- 22160207
TI  - Antiretroviral drug treatment of CNS HIV-1 infection.
AB  - The advent of combination antiretroviral treatment has had a profound impact on
      CNS HIV infection and its clinical complications, but neurological impairment
      still occurs in patients on systemically effective combination therapy, and in
      some patients it may be important to consider antiretroviral drug entry and
      effects within the CNS. There are now data on the CNS exposure for most
      antiretroviral drugs. This review focuses on the CNS pharmacokinetics and
      pharmacodynamics of antiretroviral drugs in humans, and also discusses
      controversies in this field.

PMID- 22160209
TI  - miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits
      tumor formation by targeting Bcl-2.
AB  - microRNAs (miRNAs) are small non-coding RNA molecules of 21-24 nt that regulate
      the expression of other genes by transcriptional inhibition or translational
      repression. Multiple lines of evidence suggest that miRNAs play important roles
      in tumor development and progression. We identified 24 miRNAs markedly and
      aberrantly expressed in human cervical cancer. The most significantly deregulated
      was miR-143 as determined by miRNA microarray analysis. miR-143 was introduced
      into HeLa cells and it was found that the overexpression of miR-143 significantly
      inhibited HeLa cell proliferation and promoted apoptosis; anti-miR-143 rescued
      the effects. HeLa cells transfected with pre-miR-143, pre-anti-miR-143 or control
      miRNA precursor were injected subcutaneously into the flanks of female athymic
      nude mice, and the overexpression of miR-143 suppressed the formation of tumors.
      Compared with normal cervical tissues, the levels of Bcl-2 were increased in miR
      143-downregulated tissues. Sustained overexpression of miR-143 in HeLa cells
      resulted in suppression of Bcl-2 expression, and knockdown of miR-143 by anti-miR
      143 increased Bcl-2 expression. In addition, overexpression of Bcl-2 partially
      reversed the inhibition of proliferation and promotion of apoptosis in the HeLa
      cells caused by miR-143. Furthermore, miR-143 suppressed the activity of a
      luciferase reporter carrying the 3'-UTR of Bcl-2, which was abolished by mutation
      of the predicted miR-143-binding site, indicating that Bcl-2 is a miR-143 target
      gene. Our study revealed a molecular link between miR-143 and Bcl-2. Direct
      involvement in the regulation of Bcl-2 may be one of the mechanisms through which
      miR-143 may play a role in the pathogenesis of cervical cancer.

PMID- 22160208
TI  - Upregulation of arginase-II contributes to decreased age-related myocardial
      contractile reserve.
AB  - Arginase-II (Arg-II) reciprocally regulates nitric oxide synthase (NOS) and
      offsets basal myocardial contractility. Furthermore, decreased or absent
      myocardial NOS activity is associated with a depression in myocardial contractile
      reserve. We therefore hypothesized that upregulation of Arg-II might in part be
      responsible for depressed myocardial contractility associated with age. We
      studied arginase activity/expression, NOS expression, NO production in the
      presence and absence of the arginase inhibitor S-(2-boronoethyl)-L: -cysteine
      (BEC) in old (22 months) and young (3 months) rat hearts and myocytes. The
      spatial confinement of Arg-II and NOS was determined with immuno-electron
      miocrographic (IEM) and immuno-histochemical studies. We tested the effect of BEC
      on the force frequency response (FFR) in myocytes, as well as NOS abundance and
      activity. Arginase activity and Arg-II expression was increased in old hearts
      (2.27 +/- 0.542 vs. 0.439 +/- 0.058 nmol urea/mg protein, p = 0.02). This was
      associated with a decrease in NO production, which was restored with BEC (4.54 +/
      0.582 vs. 12.88 +/- 0.432 MUmol/mg, p < 0.01). IEM illustrates increased
      mitochondrial density in old myocytes (51.7 +/- 1.8 vs. 69 +/- 2.2 * 10(6)/cm(2),
      p < 0.01), potentially contributing to increased Arg-II abundance and activity.
      Immunohistochemistry revealed an organized pattern of mitochondria and Arg-II
      that appears disrupted in old myocytes. The FFR was significantly depressed in
      old myocytes (61.42 +/- 16.04 vs. -5.15 +/- 5.65%), while inhibition of Arg-II
      restored the FFR (-5.15 +/- 5.65 vs. 70.98 +/- 6.10%). NOS-2 is upregulated
      sixfold in old hearts contributing to increased production of reactive oxygen
      species which is attenuated with NOS-2 inhibition by 1400 W (4,735 +/- 427 vs.
      4,014 +/- 314 RFU/min/mg protein, p = 0.005). Arg-II upregulation in aging rat
      hearts contributes to age-related decreased contractile function.

PMID- 22160210
TI  - Clinical worsening during long-term follow-up in inoperable chronic
      thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Pulmonary endarterectomy is the treatment of choice in chronic
      thromboembolic pulmonary hypertension (CTEPH). Modern pulmonary vasoactive
      medication (like endothelin receptor antagonists, phosphodiesterase type 5
      inhibitors, and prostacyclins) is used in patients with an inoperable disease and
      improved prognosis. We evaluate mortality and time to clinical worsening (TtCW)
      in inoperable CTEPH patients during long-term follow-up. METHODS: All 32 patients
      with inoperable CTEPH were enrolled between June 2002 and January 2009. TtCW was
      defined as the combination of death, need for intravenous pulmonary arterial
      hypertension medication, or 15% decrease in 6-minute walk distance (6-MWD)
      without improvement in functional class. The Cox proportional hazard regression
      was used to identify predictors. RESULTS: During a mean follow-up of 3.4 years
      (range = 0.2-10.2 years), 11 patients died (34%). The 1- and 3-year survival
      rates were 87 and 77%, respectively. Baseline functional class, 6-MWD, mean
      pulmonary artery pressure, and pulmonary vascular resistance were predictors for
      survival. Clinical worsening occurred in 16 patients (50%). The 1- and 3-year
      rates of freedom from clinical worsening were 74 and 60%, respectively. The only
      predictor for clinical worsening was the baseline 6-MWD. CONCLUSION: Despite the
      improvement in medical treatment of inoperable CTEPH, the mortality rate is still
      high, and clinical worsening occurred in a substantial number of patients during
      a follow-up of more than 3 years.

PMID- 22160211
TI  - Comparison of oxidized porous silicon with bare porous silicon as a photothermal
      agent for cancer cell destruction based on in vitro cell test results.
AB  - In the systematic administration of cancer, cancer markers are normally used to
      help the therapeutic agents access the cancer cells spontaneously. Therefore, it
      is essential to functionalize the surface of porous silicon (pSi) for cancer
      markers to attach well to pSi in systematic administration because most cancer
      markers does not attach easily to pSi. The thermal oxidation of pSi is adopted
      most widely as a surface functionalization technique for pSi. This study examined
      the photothermal properties and cancer cell-killing ability of oxidized pSi
      (pSiO). The temperature measurement and in vitro cell tests including the annexin
      V-fluorescein isothiocyanate (FITC) apoptosis assay tests, MTT assay tests, and
      Trypan blue cell death assay tests were performed to compare the photothermal
      properties and the cytotoxic effect of pSiO with those of pSi in combination with
      an 808-nm NIR laser. pSiO showed lower photothermal properties and a lower cell
      death rate than bare pSi. On the other hand, the pSiO treatment used in
      combination with an NIR laser treatment showed a cytotoxic effect high enough to
      kill a considerable portion of the cancer cells.

PMID- 22160212
TI  - Risk factors predicting the new symptomatic vertebral compression fractures after
      percutaneous vertebroplasty or kyphoplasty.
AB  - INTRODUCTION: Percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty
      (PKP) are effective procedures to alleviate pain caused by osteoporotic vertebral
      compression fractures (VCFs). New vertebral compression fracture (NVCF) has been
      noted as a potential late sequela of the procedures. The incidence of NVCFs and
      affecting risk factors were investigated. MATERIALS AND METHODS: The authors
      retrospectively analyzed the occurrence of NVCFs in 147 patients treated with PVP
      or PKP for osteoporotic VCFs. Possible risk factors, such as age, gender, body
      mass index, bone mineral density (BMD), location of treated vertebra, treatment
      modality, amount of bone cement injected, anterior-posterior ratio of the
      fractured vertebra, cement leakage into the disc space, and pattern of cement
      distribution, were assessed. RESULTS: Twenty-seven patients (18.4%) had
      subsequent symptomatic NVCFs with a median time to new fracture was of 70 days.
      The 1-year symptomatic fracture-free rate was 85.0% by the Kaplan-Meier estimate.
      Eighteen (66.7%) of the 27 patients had an NVCF on the adjacent vertebra.
      Significant differences (P < 0.05) were found between the NVCF and control groups
      in regard to age, treatment modality, BMD, and the proportion of cement leakage
      into the disc space. Discal cement leakage and low BMD affected on adjacent
      NVCFs. CONCLUSION: The most important risk factors affecting NVCFs were
      osteoporosis and intervertebral discal cement leakage.

PMID- 22160213
TI  - No association between Agent Orange exposure and monoclonal gammopathies.

PMID- 22160215
TI  - Fatal brain haemorrhage after MCA dissection: how aggressive should we treat?

PMID- 22160214
TI  - In vivo evaluation of white matter pathology in patients of progressive
      supranuclear palsy using TBSS.
AB  - INTRODUCTION: The purpose of this research is to study white matter (WM) changes
      in patients of progressive supranuclear palsy (PSP) using automated analysis of
      diffusion tensor imaging (DTI) indices. METHODS: This was a prospective study
      comprising of 24 patients of PSP and 26 matched healthy controls. Fractional
      anisotropy, mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD)
      changes were studied in the WM of the PSP patients using an automated analysis
      technique, tract-based spatial statistics (TBSS). Two subtypes of PSP, i.e.,
      classic Richardson's syndrome (PSP-RS) and parkinsonian type (PSP-P), were also
      compared among themselves to identify relative severity of WM changes as well as
      identify spatial distribution of the differences. Clinicoradiological correlation
      was done to determine the strength of correlation between WM abnormalities
      identified using TBSS and clinical scores. RESULTS: There were areas of
      significant abnormality seen in the frontoparietal cerebral WM, thalamus,
      midbrain tectum, superior cerebellar peduncle, and cerebellar WM. The
      abnormalities were more spatially widespread on MD and RD maps. Compared to PSP
      P, the patients of PSP-RS had more spatial abnormalities localized to the frontal
      WM. There was no correlation between the observed WM changes and clinical rating
      scales. CONCLUSIONS: The TBSS analysis showed widespread WM abnormalities in PSP
      patients including areas which have been shown to be involved in previous
      pathological studies. PSP-RS showed more severe white matter abnormality compared
      to the PSP-P subtype.

PMID- 22160216
TI  - Denitrification by plant roots? New aspects of plant plasma membrane-bound
      nitrate reductase.
AB  - A specific form of plasma membrane-bound nitrate reductase in plants is
      restricted to roots. Two peptides originated from plasma membrane integral
      proteins isolated from Hordeum vulgare have been assigned as homologues to the
      subunit NarH of respiratory nitrate reductase of Escherichia coli. Corresponding
      sequences have been detected for predicted proteins of Populus trichocarpa with
      high degree of identities for the subunits NarH (75%) and NarG (65%), however,
      with less accordance for the subunit NarI. These findings coincide with
      biochemical properties, particularly in regard to the electron donors menadione
      and succinate. Together with the root-specific and plasma membrane-bound
      nitrite/NO reductase, nitric oxide is produced under hypoxic conditions in the
      presence of nitrate. In this context, a possible function in nitrate respiration
      of plant roots and an involvement of plants in denitrification processes are
      discussed.

PMID- 22160217
TI  - Biomedical impact of splicing mutations revealed through exome sequencing.
AB  - Splicing is a cellular mechanism, which dictates eukaryotic gene expression by
      removing the noncoding introns and ligating the coding exons in the form of a
      messenger RNA molecule. Alternative splicing (AS) adds a major level of
      complexity to this mechanism and thus to the regulation of gene expression. This
      widespread cellular phenomenon generates multiple messenger RNA isoforms from a
      single gene, by utilizing alternative splice sites and promoting different exon
      intron inclusions and exclusions. AS greatly increases the coding potential of
      eukaryotic genomes and hence contributes to the diversity of eukaryotic
      proteomes. Mutations that lead to disruptions of either constitutive splicing or
      AS cause several diseases, among which are myotonic dystrophy and cystic
      fibrosis. Aberrant splicing is also well established in cancer states.
      Identification of rare novel mutations associated with splice-site recognition,
      and splicing regulation in general, could provide further insight into genetic
      mechanisms of rare diseases. Here, disease relevance of aberrant splicing is
      reviewed, and the new methodological approach of starting from disease phenotype,
      employing exome sequencing and identifying rare mutations affecting splicing
      regulation is described. Exome sequencing has emerged as a reliable method for
      finding sequence variations associated with various disease states. To date,
      genetic studies using exome sequencing to find disease-causing mutations have
      focused on the discovery of nonsynonymous single nucleotide polymorphisms that
      alter amino acids or introduce early stop codons, or on the use of exome
      sequencing as a means to genotype known single nucleotide polymorphisms. The
      involvement of splicing mutations in inherited diseases has received little
      attention and thus likely occurs more frequently than currently estimated.
      Studies of exome sequencing followed by molecular and bioinformatic analyses have
      great potential to reveal the high impact of splicing mutations underlying human
      disease.

PMID- 22160218
TI  - Functional characterization of glycine N-methyltransferase and its interactive
      protein DEPDC6/DEPTOR in hepatocellular carcinoma.
AB  - Glycine N-methyltransferase (GNMT) is a tumor suppressor for hepatocellular
      carcinoma (HCC). High rates of Gnmt knockout mice developed HCC. Epigenetic
      alteration and dysregulation of several pathways including wingless-type MMTV
      integration site (Wnt), mitogen-activated protein kinase (MAPK) and Janus kinase
      and signal transducer and activator of transcription (JAK-STAT) are associated
      with HCC development in Gnmt knockout mice. We hypothesized that GNMT may
      regulate signal transduction through interacting with other proteins directly. In
      this report, we identified a mammalian target of rapamycin (mTOR) inhibitor (DEP
      domain containing MTOR-interacting protein [DEPDC6/DEPTOR]) as a GNMT-binding
      protein by using yeast two-hybrid screening. Fluorescence resonance energy
      transfer assay demonstrated that the C-terminal half of GNMT interact with the
      PSD-95/Dlg1/ZO-1 (PDZ) domain of DEPDC6/DEPTOR. Immunohistochemical staining
      showed that 27.5% (14/51) of HCC patients had higher expression levels of
      DEPDC6/DEPTOR in the tumorous tissues than in tumor-adjacent tissues, especially
      among HCC patients with hepatitis B viral infection (odds ratio 10.3, 95%
      confidence interval [CI] 1.05-11.3) or patients with poor prognosis (death hazard
      ratio 4.51, 95% CI 1.60-12.7). In terms of molecular mechanism, knockdown of
      DEPDC6/DEPTOR expression in HuH-7 cells caused S6K and 4E-BP activation, but
      suppressed Akt. Overexpression of DEPDC6/DEPTOR activated Akt and increased
      survival of HCC cells. Overexpression of GNMT caused activation of mTOR/raptor
      downstream signaling and delayed G2/M cell cycle progression, which altogether
      resulted in cellular senescence. Furthermore, GNMT reduced proliferation of HuH-7
      cells and sensitized them to rapamycin treatment both in vitro and in vivo. In
      conclusion, GNMT regulates HCC growth in part through interacting with
      DEPDC6/DEPTOR and modulating mTOR/raptor signaling pathway. Both GNMT and
      DEPDC6/DEPTOR are potential targets for developing therapeutics for HCC.

PMID- 22160219
TI  - beta-Amyloid carrying the Dutch mutation has diverse effects on calpain-mediated
      toxicity in hippocampal neurons.
AB  - Hereditary cerebral hemorrhage with amyloidosis-Dutch type is a disorder
      associated with a missense mutation (E693Q) in the beta-amyloid (Abeta)-coding
      region of the amyloid precursor protein (APP). This familial disease is
      characterized by cognitive deficits secondary to intracerebral hemorrhage and, in
      some cases, progressive Alzheimer's disease (AD)-like dementia. Although this
      mutation was the first ever reported in the human APP gene, little is known about
      the molecular mechanisms underlying the direct toxic effects of this mutated
      Abeta on central neurons. In the present study, we assessed the role of calpain
      mediated toxicity in such effects using an AD primary culture model system. Our
      results showed that Dutch mutant Abeta (E22Q) induced calpain-mediated cleavage
      of dynamin 1 and a significant decrease in synaptic contacts in mature
      hippocampal cultures. These synaptic deficits were similar to those induced by
      wild-type (WT) Abeta. In contrast, calpain-mediated tau cleavage leading to the
      generation of a 17-kDa neurotoxic fragment, as well as neuronal death, were
      significantly reduced in E22Q Abeta-treated neurons when compared with WT Abeta
      treated ones. This complex regulation of the calpain-mediated toxicity pathway by
      E22Q Abeta could have some bearing in the pathobiology of this familial AD form.

PMID- 22160220
TI  - Insulin receptor substrate 2 (IRS2)-deficient mice show sensorineural hearing
      loss that is delayed by concomitant protein tyrosine phosphatase 1B (PTP1B) loss
      of function.
AB  - The insulin receptor substrate (IRS) proteins are key mediators of insulin and
      insulinlike growth factor 1 (IGF-1) signaling. Protein tyrosine phosphatase (PTP)
      1B dephosphorylates and inactivates both insulin and IGF-1 receptors. IRS2
      deficient mice present altered hepatic insulin signaling and beta-cell failure
      and develop type 2-like diabetes. In addition, IRS2 deficiency leads to
      developmental defects in the nervous system. IGF1 gene mutations cause syndromic
      sensorineural hearing loss in humans and mice. However, the involvement of IRS2
      and PTP1B, two IGF-1 downstream signaling mediators, in hearing onset and loss
      has not been studied. Our objective was to study the hearing function and
      cochlear morphology of Irs2-null mice and the impact of PTP1B deficiency. We have
      studied the auditory brainstem responses and the cochlear morphology of systemic
      Irs2-/-Ptpn1+/+, Irs2+/+Ptpn1-/- and Irs2-/-Ptpn1-/- mice at different postnatal
      ages. The results indicated that Irs2-/-Ptpn1+/+ mice present a profound
      congenital sensorineural deafness before the onset of diabetes and altered
      cochlear morphology with hypoinnervation of the cochlear ganglion and aberrant
      stria vascularis, compared with wild-type mice. Simultaneous PTP1B deficiency in
      Irs2-/-Ptpn1-/- mice delays the onset of deafness. We show for the first time
      that IRS2 is essential for hearing and that PTP1B inhibition may be useful for
      treating deafness associated with hyperglycemia and type 2 diabetes.

PMID- 22160223
TI  - [Sensitive skin].

PMID- 22160221
TI  - Hematopoietic CC-chemokine receptor 2 (CCR2) competent cells are protective for
      the cognitive impairments and amyloid pathology in a transgenic mouse model of
      Alzheimer's disease.
AB  - Monocytes emigrate from bone marrow, can infiltrate into brain, differentiate
      into microglia and clear amyloid beta (Abeta) from the brain of mouse models of
      Alzheimer's disease (AD). Here we show that these mechanisms specifically require
      CC-chemokine receptor 2 (CCR2) expression in bone marrow cells (BMCs). Disease
      progression was exacerbated in APP(Swe)/PS1 mice (transgenic mice expressing a
      chimeric amyloid precursor protein [APPSwe] and human presenilin 1 [PS1])
      harboring CCR2-deficient BMCs. Indeed, transplantation of CCR2-deficient BMCs
      enhanced the mnesic deficit and increased the amount of soluble Abeta and
      expression of transforming growth factor (TGF)-beta1 and TGF-beta receptors. By
      contrast, transplantation of wild-type bone marrow stem cells restored memory
      capacities and diminished soluble Abeta accumulation in APP(Swe)/PS1 and
      APP(Swe)/PS1/CCR2-/- mice. Finally, gene therapy using a lentivirus-expressing
      CCR2 transgene in BMCs prevented cognitive decline in this mouse model of AD.
      Injection of CCR2 lentiviruses restored CCR2 expression and functions in
      monocytes. The presence of these cells in the brain of non-irradiated
      APP(Swe)/PS1/CCR2-/- mice supports the concept that they can be used as gene
      vehicles for AD. Decreased CCR2 expression in bone marrow-derived microglia may
      therefore play a major role in the etiology of this neurodegenerative disease.

PMID- 22160224
TI  - [Neuropeptides and their receptors as a molecular explanation for sensitive
      skin].
AB  - The concept of sensitive skin represents a symptom of physiological reactions
      rather than a disease entity. According to epidemiological studies, up to 50% of
      adults report on sensitivity of the face with various distinctive symptoms such
      as prickling, burning, tingling, pain or itching. These sensations can be
      mediated by receptors expressed on neurons and keratinocytes. The heat receptor
      TRPV1 is for example involved in nociception and mediates not only warmth but
      also burning. Furthermore, neurotrophins and exogenic factors such as stress may
      have a biological role as discussed in this review.

PMID- 22160225
TI  - [New insights into the pathogenesis of sensitive skin].
AB  - Many persons in the developed countries report sensitive skin. Persons with
      sensitive skin have a predisposition to several skin diseases, most importantly
      dry skin, but also atopy, seborrheic dermatitis, acne vulgaris, rosacea, and
      perioral dermatitis. Their complaints may be triggered by environmental factors
      such as low temperature, wind, high temperature, sun exposure and stress. Various
      skin care products and cosmetics are not tolerated. A disturbed skin barrier
      function and reduced stratum corneum water content are most important in the
      pathophysiology of sensitive skin. Environmental factors and cosmetics may induce
      irritation of the skin because of the disturbed skin barrier. Of further
      importance for the pathogenesis are neurogenic factors including stress and hyper
      excitability. Mechanisms in signal transduction involve cytokines and
      neurotransmitters, but the exact pathways are unknown.

PMID- 22160226
TI  - [Principles of treatment and protection for sensitive skin].
AB  - Patients with sensitive skin complain of itching, burning, pricking or stretching
      sensations of the skin and even pain following application of external agents or
      exposure to certain environmental factors. In most cases of sensitive skin the
      cause remains unclear and allergic contact dermatitis, toxic irritant dermatitis
      or contact urticaria can be diagnosed only in a few patients. After exclusion of
      known exogenous or endogenous causes patients should be informed on the
      characteristics of sensitive skin. Potential irritating substances and procedures
      should be extensively avoided or utilized cautiously.

PMID- 22160227
TI  - [Trivial injury to the sole of the foot].
AB  - A 67-year-old male patient noticed a foreign body sensation following a trivial
      trauma to the sole of the left foot approximately 4 months before presentation.
      The existing skin alteration had been self-treated with pumice stone and an
      unidentifiable wart tincture. The examination revealed an approximately 2 cm in
      diameter macula on the left heel with a zonal construction. The periphery was
      formed by a polycyclic dark brown ring which enclosed a reddish skin colored
      macula with several minute erosions. Dermatoscopy revealed an unspecific pattern
      with polymorphic vessels in the center. The peripheral ring showed radially
      running streaks as well as a parallel track-like pattern in one region. Histology
      revealed this to be an acral melanoma. A melanoma should always be included in
      the differential diagnostic considerations of atypical acral lesions. A biopsy
      should always be carried by unclear clinical and light microscopical findings out
      to enable a final diagnosis.

PMID- 22160228
TI  - [Malignant lymphoma of the skin: update on diagnostics and therapy of primary
      cutaneous B-cell lymphoma].
AB  - The diagnosis of primary cutaneous B-cell lymphoma is made based principally on
      the results of histological investigations and staging. For an exact staging
      abdominal sonography and chest X-ray examinations and for appropriate clinical
      symptoms special investigations as well as radiological imaging procedures
      including PET are indicated in addition to conventional laboratory
      investigations. For therapy rituximab is normally administered as monotherapy in
      order to avoid over therapy of indolent lymphoma. Further options are
      radiotherapy and new approaches with electrochemotherapy as well as pegylated
      doxorubicin.

PMID- 22160230
TI  - Pheromone synthesis.
AB  - Various aspects of pheromone synthesis were reviewed by analyzing 61 synthetic
      examples from 9 different structural categories of pheromones. Syntheses executed
      with new methodologies such as organoborane reactions, organotransition metal
      chemistry including ring-closing olefin metathesis, asymmetric epoxidations and
      dihydroxylations, and enzymatic reactions are selected to illustrate the
      usefulness of modern new reactions.

PMID- 22160229
TI  - The dopaminergic system in patients with functional dyspepsia analysed by single
      photon emission computed tomography (SPECT) and an alpha-methyl-para-tyrosine
      (AMPT) challenge test.
AB  - PURPOSE: Functional dyspepsia (FD) is a chronic condition characterized by upper
      abdominal symptoms without an identifiable cause. While the serotonergic system
      is thought to play a key role in the regulation of gut physiology, the role of
      the dopaminergic system, which is important in the regulation of visceral pain
      and stress, is under-studied. Therefore, this study investigated the dopaminergic
      system and its relationship with drinking capacity and symptoms in FD patients.
      METHODS: In FD patients and healthy volunteers (HV) the dopaminergic system was
      investigated by in-vivo assessment of central dopamine D2 receptors (D2Rs) with
      [(123)I]IBZM SPECT and by an acute, but reversible, dopamine depletion alpha
      methyl-para-tyrosine (AMPT) challenge test. A nutrient drink test was performed
      to investigate the association between maximal ingested volume, evoked symptoms,
      and D2Rs. RESULTS: The HV subjects comprised 12 women and 8 men (mean age 31 +/-
      3 years), and the FD patients comprised 5 women and 3 men (mean age 39 +/- 5
      years). The FD patients had a lower left plus right average striatal binding
      potential (BP(NP)) for the caudate nucleus (p = 0.02), but not for putamen (p =
      0.15), which in the FD patients was correlated with maximal ingested volume (r =
      0.756, p = 0.03). The D2R BP(NP) in the putamen was correlated with nausea (r =
      0.857, p = 0.01). The acute dopamine depletion test, however, failed to reveal
      differences in prolactin release between the FD patients and the HV subjects.
      CONCLUSION: These preliminary data suggest that chronic rather than acute
      alterations in the dopaminergic system may be involved in the pathogenesis of FD.
      Further studies are required to reproduce our novel findings and to evaluate to
      what extent the dopaminergic changes may be secondary to abnormalities in
      serotonergic pathways.

PMID- 22160231
TI  - Lepidopteran sex pheromones.
AB  - As a consequence of the diversity of Lepidoptera, including 150,000 described
      species, interesting species-specific sex pheromone systems are exhibited in this
      insect group. The quite varied pheromones, which have been identified from female
      moths of nearly 530 species from around the world, are classified into groups of
      Type I (75%), Type II (15%), and miscellaneous (10%), according to their chemical
      structures. Additionally, many pheromones produced by male moths and butterflies
      have been known. While new sex pheromones from about 70 lepidopteran species have
      been reported in the last five years utilizing GC-EAD, GC-MS, LC, and NMR, our
      information about the pheromones is still rudimentary, and these kinds of
      semiochemicals remain an exciting research target for natural product chemistry.
      In addition to the overview of their chemical structures, this chapter deals with
      current methods for their identification. Furthermore, an actual application of
      the synthetic pheromones for pest control is briefly introduced.

PMID- 22160232
TI  - Insect pheromone biosynthesis.
AB  - Pheromones are utilized by many insects in a complex chemical communication
      system. This review will look at the biosynthesis of sex and aggregation
      pheromones in the model insects, moths, flies, cockroaches, and beetles. The
      biosynthetic pathways involve altered pathways of normal metabolism of fatty
      acids and isoprenoids. Endocrine regulation of the biosynthetic pathways will
      also be reviewed for the model insects. A neuropeptide named pheromone
      biosynthesis activating neuropeptide regulates sex pheromone biosynthesis in
      moths. Juvenile hormone regulates pheromone production in the beetles and
      cockroaches, while 20-hydroxyecdysone regulates pheromone production in the
      flies.

PMID- 22160233
TI  - Hymenopteran semiochemicals.
AB  - Hymenoptera is a very large and diverse insect order that includes the majority
      of both the social and the parasitic insects. With such diversity comes a variety
      and complexity of semiochemicals that reflect the varied biology of members of
      this order. This chapter reviews the chemical identification of pheromones and
      semiochemicals in the order Hymenoptera since 1990. For this review, the species
      in Hymenoptera have been classified as solitary, parasitic, or social. The
      chemical diversity of semiochemicals in Hymenoptera and future trends in
      pheromone identification are also discussed.

PMID- 22160234
TI  - Chemical defense strategies of marine organisms.
AB  - The diverse habitats of the marine environment and the adaptation required to
      live either in the open water or attached to a substrate resulted in various
      defense strategies. This review covers different ways how organisms from the
      plankton can maintain a chemical defense as well as the dynamic chemical defense
      strategies of benthic organisms. It opens with a detailed discussion of recent
      studies of chemical defenses among organisms floating in the open water. These
      defenses include the production of toxins by harmful algal blooms as well as the
      rapid production of defensive metabolites from non-toxic precursors upon cell
      disruption. A comprehensive account of recent advances in the field of dynamic
      chemical defense strategies of benthic organisms is then presented. It includes
      the known examples of activated defense based on the enzymatic transformation of
      storage metabolites as well as induced chemical defense strategies. These
      strategies depend on the recognition of signals from an herbivore or pathogen,
      followed by the up-regulation of the biosynthesis of metabolites involved in the
      chemical defense.

PMID- 22160236
TI  - Pulsed rf-GD-TOFMS for depth profile analysis of ultrathin layers using the
      analyte prepeak region.
AB  - Direct solid analysis of ultrathin layers is investigated using pulsed
      radiofrequency (rf) glow discharge (GD) time-of-flight mass spectrometry (TOFMS).
      In particular, previous studies have always integrated the detected ion signals
      in the afterglow region of the rf-GD pulse, which is known to be the most
      sensitive one. Nevertheless, the analytical capabilities of other pulse time
      regions have not been evaluated in detail. Therefore, in this work, we
      investigate the analyte prepeak region, which is the pulse region where the
      analyte ions peak after the initial sputtering process of each GD pulse, aiming
      at obtaining improved depth profile analysis with high depth resolution and with
      minimum polyatomic spectral interferences. To perform these studies, challenging
      ultrathin Si-Co bilayers deposited on a Si substrate were investigated. The
      thickness of the external Si layer was 30 nm for all the samples, whilst the
      internal Co layer thicknesses were 30, 10, 5, 2 and 1 nm, respectively. It should
      be remarked that the top layer and the substrate have the same matrix composition
      (Si > 99.99%). Therefore, the selected samples are suitable to evaluate the
      response of the Si ion signal in the presence of an ultrathin Co layer as well as
      the possible oxygen contaminations or its reactions. Additionally, these samples
      have been evaluated using time-of-flight secondary ion mass spectrometry, and the
      results compare well to those obtained by our pulsed rf-GD time-of-flight mass
      spectrometry results.

PMID- 22160235
TI  - Monitoring induced gene expression of single cells in a multilayer microchip.
AB  - We present a microfluidic system that facilitates long-term measurements of
      single cell response to external stimuli. The difficulty of addressing cells
      individually was overcome by using a two-layer microfluidic device. The top layer
      is designed for trapping and culturing of cells while the bottom layer is
      employed for supplying chemical compounds that can be transported towards the
      cells in defined concentrations and temporal sequences. A porous polyester
      membrane that supports transport and diffusion of compounds from below separates
      the microchannels of both layers. The performance and potential of the device are
      demonstrated using human embryonic kidney cells (HEK293) transfected with an
      inducible gene expression system. Expression of a fluorescent protein (ZsGreen1
      DR) is observed while varying the concentration and exposure time of the inducer
      tetracycline. The study reveals the heterogeneous response of the cells as well
      as average responses of tens of cells that are analyzed in parallel. The
      microfluidic platform enables systematic studies under defined conditions and is
      a valuable tool for general single cell studies to obtain insights into
      mechanisms and kinetics that are not accessible by conventional macroscopic
      methods.

PMID- 22160237
TI  - Quantification of plasma homocitrulline using hydrophilic interaction liquid
      chromatography (HILIC) coupled to tandem mass spectrometry.
AB  - Homocitrulline (HCit), an amino acid formed by the carbamylation of epsilon-amino
      groups of lysine residues, is considered a promising biomarker for monitoring
      diseases such as chronic renal failure and atherosclerosis. This paper describes
      a tandem mass spectrometric method for total, protein-bound and free HCit
      measurement in plasma samples. HCit was separated from other plasma components by
      hydrophilic interaction liquid chromatography. Detection was achieved by
      monitoring transitions of 190.1 > 127.1 and 190.1 > 173.1 for HCit, and 183.1 >
      120.2 for d(7)-citrulline used as internal standard. This method allowed HCit
      quantification within 5.2 min and was precise (inter-assay CV < 5.85%), accurate
      (mean recoveries ranging from 97% to 106%), and exhibited a good linearity from
      10 nmol/L to 1.6 MUmol/L. Plasma samples from control and uremic mice (n = 10)
      were analyzed. In control mice, mean total plasma HCit concentration was 0.78 +/-
      0.12 MUmol/mol amino acids, whereas it was increased 2.7-fold in uremic mice
      plasma, reaching 2.10 +/- 0.50 MUmol/mol amino acids (p < 0.001). In conclusion,
      this method exhibits good analytical performances and meets the criteria of
      sensitivity suitable for HCit concentration assessment in plasma samples.

PMID- 22160238
TI  - Saliva secretion rate and acidity in a group of physically disabled older care
      home residents.
AB  - A growing number of older people have teeth, which are vulnerable to oral
      diseases. To maintain good oral health, an adequate amount of saliva should be
      secreted and the saliva should possess adequate buffer capacity. The study aim
      was to investigate the associations of saliva secretion rate and acidity with
      gender, age, and some medical characteristics in a convenience sample of
      physically disabled older care home residents. In 20 male and 30 female
      physically disabled older care home residents with a mean age of 78.1 +/- 9.7
      years, the resting, chewing-stimulated, and acid-stimulated whole saliva
      secretion rate and acidity, as well as the main medical diagnosis and the number
      of medications used, were registered. Resting, chewing-stimulated and acid
      stimulated whole saliva secretion rates were lower in women than in men and
      negatively associated with age and the number of medications used. In female
      residents, the acidity of acid-stimulated whole saliva was negatively associated
      with the acid-stimulated whole saliva secretion rate. In residents aged >70
      years, the acidity of resting whole saliva was positively associated with age.
      The acidity of acid-stimulated whole saliva of all residents was positively
      associated with the number of medications used.

PMID- 22160239
TI  - Dobutamine for patients with severe heart failure: a systematic review and meta
      analysis of randomised controlled trials.
AB  - PURPOSE: Dobutamine is recommended for patients with severe heart failure;
      however uncertainty exists as to its effect on mortality. This study aims to
      critically review the literature to evaluate whether dobutamine, compared with
      placebo or standard care, is associated with lower mortality and a range of
      secondary outcomes, in patients with severe heart failure. METHODS: A systematic
      review and meta-analysis of randomised controlled trials was performed. PubMed,
      EMBASE, the Cochrane Central Trials Registry, the metaRegister of Controlled
      Trials and bibliographies of retrieved articles were searched. Randomised trials
      comparing dobutamine with placebo or standard care, in human, adult patients with
      severe heart failure, were included if they reported at least one outcome of
      interest. Data regarding trial validity, methodological processes and clinical
      outcomes were extracted, and a meta-analysis was performed. RESULTS: Fourteen
      studies, with 673 participants, met the inclusion criteria and were included; 13
      studies reported mortality. There was minimal heterogeneity (I(2) = 4.5%). The
      estimate of the odds ratio for mortality for patients with severe heart failure
      treated with dobutamine compared with standard care or placebo was 1.47 (95%
      confidence interval 0.98-2.21, p = 0.06). CONCLUSIONS: This meta-analysis showed
      that dobutamine is not associated with improved mortality in patients with heart
      failure, and there is a suggestion of increased mortality associated with its
      use, although this did not reach the conventional level of statistical
      significance. Further research to define the role of dobutamine in treatment of
      severe heart failure should be a priority.

PMID- 22160240
TI  - "The beach position": crossed legs as a marker for a favourable clinical course
      in neurological intensive care unit patients.

PMID- 22160241
TI  - Principal component 1 score calculated from metabolic syndrome diagnostic
      parameters is a possible marker for the development of metabolic syndrome in
      middle-aged Japanese men without treatment for metabolic diseases.
AB  - PURPOSE: The risk of metabolic syndrome (MetS) is assessed based on the presence
      of risk factors that include dyslipidemia, hyperglycemia, hypertension and
      obesity. In this study, we assessed the risk of MetS using principle component
      (PC) analysis of MetS diagnostic parameters and examined whether the resulting
      eigenvalues are associated with the circulating concentrations of inflammatory
      cytokines [interleukin (IL)-1beta and IL-6] and a marker for insulin sensitivity
      (adiponectin) in middle-aged Japanese men without treatment for metabolic
      diseases. MATERIALS: We conducted a cross-sectional study of 308 Japanese men
      without treatment for metabolic diseases aged 40-69 years who participated in
      health checkups in Japan. We calculated the PC1 score from the following MetS
      diagnostic parameters: body mass index (BMI), fasting blood glucose, diastolic
      blood pressure, triacylglycerol and high-density lipoprotein cholesterol. We
      compared the relationship between PC1 scores and other clinical parameters,
      including IL-1beta, IL-6 and adiponectin, by Spearman's rank correlation
      coefficient analyses and Jonckheere-Terpstra test. RESULTS: The associations for
      most clinical parameters were higher with the PC1 score than with other MetS
      diagnostic parameters. Homeostasis model assessment-insulin resistance, an index
      of insulin resistance, showed stronger associations with PC1 score than with MetS
      diagnostic parameters. Significant associations for IL-1beta, IL-6 and
      adiponectin were observed with the PC1 score, BMI and triacylglycerol; these
      associations were higher with the PC1 score than with BMI and triacylglycerol.
      CONCLUSIONS: The present results show that the PC1 score is closely associated
      with parameters of MetS, inflammation and insulin resistance.

PMID- 22160242
TI  - Scram1 is a modifier of spinal cord resistance for astrocytoma on mouse Chr 5.
AB  - Tumor location can profoundly affect morbidity and patient prognosis, even for
      the same tumor type. Very little is known about whether tumor location is
      determined stochastically or whether genetic risk factors can affect where tumors
      arise within an organ system. We have taken advantage of the Nf1-/+;Trp53-/+cis
      mouse model of astrocytoma/glioblastoma to map genetic loci affecting whether
      astrocytomas are found in the spinal cord. We identify a locus on distal Chr 5,
      termed Scram1 for spinal cord resistance to astrocytoma modifier 1, with a LOD
      score of 5.0 and a genome-wide significance of P < 0.004. Mice heterozygous for
      C57BL/6J*129S4/SvJae at this locus show less astrocytoma in the spinal cord
      compared to 129S4/SvJae homozygous mice, although we have shown previously that
      129S4/SvJae mice are more resistant to astrocytoma than C57BL/6J. Furthermore,
      the astrocytomas that are found in the spinal cord of Scram1 heterozygous mice
      arise in older mice. Because spinal cord astrocytomas are very rare and difficult
      to treat, a better understanding of the genetic factors that govern astrocytoma
      in the spine may lead to new targets of therapy or prevention.

PMID- 22160243
TI  - A systematic review of the indications for genetic testing and prophylactic
      gastrectomy among patients with hereditary diffuse gastric cancer.
AB  - BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is a familial cancer
      syndrome specifically associated with germline mutations to the E-cadherin (CDH1)
      gene. HDGC is characterized by autosomal dominance and high penetrance and a high
      cumulative risk for advanced gastric cancer. Our purpose in this study was to
      identify and synthesize findings from all articles on: (1) current
      recommendations for CDH1 screening and prophylactic gastrectomy; (2) CDH1 testing
      results in HDGC patients; and (3) prophylactic gastrectomy results in HDGC
      patients. METHODS: Systematic electronic literature searches were conducted using
      Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1985
      to 2009. RESULTS: Seventy articles were included in this review. Among patients
      with a positive family history of gastric cancer, 1085 were screened from 454
      families, and 38.4% tested positive. Mutation-positive families also had a
      considerable family history of breast and colon cancer. Of the 322 patients
      screened for CDH1 mutations by current HDGC screening criteria, 29.2% tested
      positive. Among the 76.8% of patients who underwent prophylactic gastrectomy
      following positive CDH1 test results, 87.0% had positive final histopathology
      results and 64.6% had signet ring cells identified. Some of the patients with
      negative final histopathology results had opted to undergo prophylactic
      gastrectomy prior to CDH1 testing, and were ultimately found to be negative for
      CDH1 mutations. CONCLUSION: CDH1 mutation testing in families with a history of
      gastric cancer and prophylactic gastrectomy in mutation-positive patients are
      recommended for the management of HDGC.

PMID- 22160244
TI  - Three-week combination chemotherapy with S-1 and cisplatin as first-line
      treatment in patients with advanced gastric cancer: a retrospective study with
      159 patients.
AB  - BACKGROUND: Doses and schedules of the combination of S-1 and cisplatin for the
      treatment of advanced gastric cancer (AGC) have not been standardized. We
      therefore evaluated the efficacy and feasibility of a 3-week schedule of S-1 and
      cisplatin in patients with AGC, as well as assessing factors prognostic of
      patient outcomes. METHODS: A total of 159 patients with AGC were treated with S-1
      (40 mg/m(2) bid on days 1-14) and cisplatin (60 mg/m(2) IV on day 1) between
      January 2004 and December 2008. RESULTS: Median follow-up duration was 20.0
      months (range, 11.4-48.5 months), during which time 129 patients (81.1%) died.
      Patients received a median 6 cycles of chemotherapy (range, 1-19 cycles). Among
      the 59 patients with measurable disease, 1 achieved a complete response (1.7%)
      and 24 (40.7%) had partial responses, giving an overall response rate of 42.4%
      (95% CI, 23.0-61.8%). The median progression-free survival (PFS) was 5.8 months
      (95% CI, 4.8-6.9 months), and the median overall survival (OS) was 11.3 months
      (95% CI, 9.6-13.0 months). Multivariate analysis showed that initial metastasis,
      bone metastasis, and liver metastasis were independent prognostic factors for
      reduced PFS, whereas poor performance status, initial metastasis, and bone
      metastasis were prognostic for reduced OS. Application of a previous prognostic
      model showed that observed PFS and OS survival curves for patients in various
      risk groups differed significantly (P < 0.001 each). CONCLUSIONS: A 3-week
      regimen of S-1 plus cisplatin was active and well tolerated as first-line
      treatment in patients with AGC. Disease status and bone metastasis were the most
      important prognostic factors.

PMID- 22160245
TI  - Persistence of biological traces in gun barrels--an approach to an experimental
      model.
AB  - Traces of backspatter in gun barrels after homicidal or suicidal contact shots
      may be a valuable source of forensic evidence. Yet, a systematic investigation of
      the persistence and durability of DNA from biological traces in gun barrels is
      lacking. Our aim was to generate a realistic model to emulate blood and tissue
      spatters in gun barrels generated by contact gunshots at biological targets and
      to analyse the persistence and typability of DNA recovered from such stains.
      Herein, we devise and evaluate three different models for the emulation of
      backspatter from contact shots: a gelatine-based model with embedded blood bags,
      a model based on a spongious matrix soaked with blood and covered with a thin
      plastic membrane and a head model consisting of an acrylic half sphere filled
      with ballistic gelatine and with blood bags attached to the sphere under a 3-mm
      silicone layer. The sampling procedure for all three models: a first shot was
      fired with several types of guns at each model construction and subsequently a
      second shot was fired at a backstop. Blood samples were collected after each shot
      by probing the inner surface of the front and rear end of the respective gun
      barrel with a sterile swab. DNA was then extracted and quantified and up to 20
      different short tandem repeat (STR) systems were amplified to generate DNA
      profiles. Although DNA quantity and STR typing results were heterogenous between
      the models, all models succeeded in delivering full STR profiles even after more
      than one shot. We conclude that biological traces in gun barrels are robust and
      accessible to forensic analysis and that systematic examination of the inside of
      gun barrels may be advisable for forensic casework.

PMID- 22160246
TI  - Improvement in psoriasis after treatment with the glucagon-like peptide-1
      receptor agonist liraglutide.
AB  - A 59-year old man with moderate and stable psoriasis through 15 years was
      admitted to our Department with inadequately controlled type 2 diabetes.
      Treatment was initiated with the glucagon-like peptide-1 receptor (GLP-1R)
      agonist liraglutide. The patient experienced marked improvement in his psoriasis
      immediately after the start of liraglutide treatment. Itching stopped within
      days, scaling was reduced and spots of normal skin emerged. After 3 months,
      psoriasis was still improving. Excellent glycaemic control and a weight loss of
      approximately 8 kg over 3 months were moreover obtained. The patient had
      previously been well controlled in his diabetes without improvement in psoriasis,
      and the effect of liraglutide on psoriasis started before weight loss occurred.
      We discuss the possibility of a direct anti-inflammatory effect of liraglutide in
      psoriasis as well as indirect effects through improvement in comorbidities such
      as overweight. Randomized clinical trials are needed to reveal whether GLP-1R
      agonists represent a new therapeutic option for psoriasis.

PMID- 22160247
TI  - Association between EPCs count and rate of coronary revascularization in
      asymptomatic type 2 diabetic patients.
AB  - Coronary arterial disease (CAD) is common in diabetic patients, and endothelial
      progenitor cells (EPCs) are considered a surrogate marker for CAD, but
      controversies regarding this issue still remain. We investigated the potential
      clinical role of EPCs during coronary screening in asymptomatic type 2 diabetic
      patients screened with cardiovascular magnetic resonance (CMR). A total of 100
      asymptomatic type 2 diabetic subjects (51 men and 49 women) were enrolled.
      Clinical and laboratory parameters, including EPCs (CD34(+)/CD133(+)/VEGFR-2(+))
      count, were evaluated and CMR was performed. A total of 51 patients [silent
      myocardial infarction (n = 3), inducible ischemia (n = 11), suspected CAD (n =
      37)] had abnormal finding on CMR. Of the 20 patients who later underwent invasive
      coronary angiography, 8 were treated with revascularization. Fifty-one subjects
      with abnormal finding on CMR were divided into two groups [subjects with
      revascularization (group I, n = 8) vs. without revascularization (group II, n =
      43)]. Group I had a significantly increased EPCs level than group II (833 vs.
      415, P = 0.027). Multivariate logistic regression analysis revealed that an
      increased EPCs level (OR = 1.003, P = 0.024) and a high body-mass index (OR =
      1.907, P = 0.028) were independently correlated with revascularization. In our
      study, increased EPCs count is associated with performing revascularization in
      asymptomatic type 2 diabetic patients, and that increased EPCs count can provide
      clinically important information while performing intervention.

PMID- 22160248
TI  - Vicilin genes of Vigna luteola: structure, organization, expression, and
      variation.
AB  - Two different but related sequences that encode Vigna luteola 7S vicilins were
      isolated and characterized. The sequences differ by two nucleotide substitutions,
      each of which results in an amino acid replacement. This low level of divergence
      suggests that a recent gene duplication has occurred. Both variants are expressed
      in cDNA populations; therefore, neither gene is a pseudogene. Both copies were
      present in all individuals (72) analyzed using real-time PCR and TaqMan probes.
      Segregation was not observed. The two sequences are not independent alleles.
      Vicilin genomic sequences of 11 specimens from six geographic locations were
      determined. No polymorphic sites were identified in either of the two gene
      copies. This lack of polymorphism suggests that either a population bottleneck or
      selection has occurred. The genetic structure, expression patterns, and protein
      composition of the V. luteola vicilins were compared to those of other legume
      vicilins.

PMID- 22160249
TI  - Association of CYP19 gene polymorphism with vertebral fractures in Japanese
      postmenopausal women.
AB  - This study investigates aromatase gene polymorphism, which might influence bone
      strength in terms of mineral density and quality. We explored the relationship
      between CYP19 polymorphisms and vertebral fractures in postmenopausal Japanese
      women. In addition, we compared estrogen and testosterone levels in Japanese
      postmenopausal women with and without fractures. Osteoporotic postmenopausal
      women showed higher incidences of vertebral fractures than osteopenic women or
      women with normal lumbar bone mineral density (L2-4 BMD). Estrogen concentrations
      in postmenopausal women were associated with BMD; however, no association was
      found between sex hormone levels and the presence of fractures. The C allele
      rs2470152 was significantly associated with increased risk of vertebral fractures
      (P = 0.04), whereas none of the CYP19 polymorphisms showed differences in sex
      steroid levels between subjects with and without fractures. Allelic variants of
      aromatase genes appear to interact to influence the risk of vertebral fractures
      in postmenopausal Japanese women.

PMID- 22160251
TI  - A thousand new year's greetings from the ESNR.

PMID- 22160250
TI  - Fasudil, a Rho-kinase inhibitor, protects against excessive endurance exercise
      training-induced cardiac hypertrophy, apoptosis and fibrosis in rats.
AB  - Excessive endurance exercise training (EEET) is accompanied by cardiac
      remodeling, changes in ventricular function and increased heart failure risk.
      Fasudil, a potent Rho-kinase inhibitor, has been demonstrated to blunt
      cardiomyocyte hypertrophy, cardiac remodeling, and heart failure progression in
      pre-clinical trials and has been approved for clinical use in Japan. We examined
      the in vivo bioefficacy of fasudil against EEET-induced cardiac remodeling and
      the underlying molecular mechanisms. Male Sprague-Dawley rats were randomly
      divided into three groups: sedentary control (SC), EEET, and EEET with fasudil
      treatment (EEET-F). Rats in EEET and EEET-F groups ran on a motorized treadmill
      for 12 weeks. The results revealed that EEET increased myocardial hypertrophy (LV
      weight/tibial length), myocyte cross-sectional area, hypertrophy-related pathways
      (IL6/STAT3-MEK5-ERK5, calcineurin-NFATc3, p38 and JNK MAPK), hypertrophic markers
      (ANP/BNP), pro-apoptotic molecules (cytochrome C, cleaved caspase-3 and PARP),
      and fibrosis-related pathways (FGF-2-ERK1/2) and fibrosis markers (uPA, MMP-9 and
      -2). These pathways were then expressed lower in the EEET-F group when compared
      with the EEET group. The cardiac hypertrophic level, apoptotic pathway and
      fibrosis signaling were further inhibited in the fasudil-treated group. We
      systematically investigated the possible signaling pathways leading to EEET
      induced cardiac hypertrophy, apoptosis and fibrosis. We also provide evidence for
      the novel function of fasudil in suppressing EEET-induced cardiac remodeling and
      impairment by multiple mechanisms, which suggests that the RhoA signaling pathway
      contributes to EEET-induced cardiac remodeling and dysfunction.

PMID- 22160252
TI  - Effect of combined chlorhexidine gluconate and neosporin on experimental
      keratitis with two pathogenic strains of Acanthamoeba.
AB  - Acanthamoeba keratitis (AK) is a painful, sight-threatening, and difficult-to
      treat corneal infection caused by the ubiquitous free-living amoebae Acanthamoeba
      species. The aim of the present study was to compare the severity of keratitis,
      caused by Acanthamoeba hatchetii and Acanthamoeba castellanii infections, and to
      assess the therapeutic effects of combined chlorhexidine (CHX) and Neosporin(r)
      treatment in rats. The rats were first divided into two groups, in which the eyes
      of the animals were infected with A. hatchetii or A. castellanii trophozoites. On
      day 5, all corneas were examined in order to determine the degree of infection
      (grade 0 to 3), and animals were divided into two new groups, treatment and
      infected control groups. The treatment was continued for 28 days, followed by
      excision and histological evaluation of the corneas. In conclusion, the clinical
      picture progressed more rapidly and severely in eyes infected by A. castellanii,
      while it was non-invasive and slower to progress with A. hatchetii. Moreover,
      eyes infected by A. hatchetii responded quicker and more positively to therapy,
      consistent with its clinical course, while a longer recovery was seen with A.
      castellanii. Histological examinations revealed the presence of A. castellanii
      and A. hatchetii trophozoites in the stroma of eyes of the treatment and control
      groups. As a result, our findings suggest that a combination of Neosporin with
      lower doses of CHX may be beneficial to treat patients with early diagnosis of
      AK.

PMID- 22160255
TI  - Rituximab in combination with CHOP chemotherapy for the treatment of diffuse
      large B cell lymphoma in China: a 10-year retrospective follow-up analysis of 437
      cases from Shanghai Lymphoma Research Group.
AB  - The purpose of the study is to evaluate the 10 years follow-up of the efficacy in
      Chinese patients receiving cyclophosphamide, doxorubicin/epirubicin, vincristine,
      and prednisone (CHOP) or rituximab plus CHOP (R-CHOP) regimen as the initial
      treatment for diffuse large B cell lymphoma (DLBCL). We have retrospectively
      analyzed 437 patients with DLBCL who were newly diagnosed and received CHOP or R
      CHOP regimen in six university hospitals and closely followed up after the
      completion of treatment. For all patients, there were significant differences
      between R-CHOP and CHOP for overall survival (OS) (median follow-up 86 months,
      84.1% vs 70.2%, p = 0.018) and progression-free survival (PFS) (81.5% vs 66.7%, p
      = 0.015), while elder patients (>60 years old) received higher OS (median follow
      up 66 months, 80.7% vs 53.0%, p = 0.011). But for younger patients (<=60 years
      old), the treatments with rituximab did not demonstrate a significant effect on
      OS (85.5% vs 79.4%, p = 0.428). In the R-CHOP group, International Prognostic
      Index (IPI) distinguished three risk groups instead of four risk groups. But in
      the CHOP group, IPI still distinguished four risk groups. Furthermore, for 212 of
      437 patients diagnosed with extranodal involvement DLBCL, R-CHOP regimen provided
      a longer OS than CHOP regimen did (OS, 89.9% vs 71.7%, p = 0.014). Moreover,
      patients with extranodal lymphoma had a significant longer survival in rituximab
      era (OS, 89.9% vs 79.2% for extranodal and nodal, respectively; p = 0.048). The
      results of this large-scale study suggested that R-CHOP provided a greater
      survival benefit in the initial treatment of DLBCL. As for the patients with
      extranodal lymphoma, R-CHOP was also a good choice as first-line treatment.
      Extranodal disease seems to be an independent good prognostic factor in rituximab
      era.

PMID- 22160253
TI  - Larvicidal and repellent activity of Hyptis suaveolens (Lamiaceae) essential oil
      against the mosquito Aedes albopictus Skuse (Diptera: Culicidae).
AB  - Lamiaceae have traditionally been used in developing countries for their
      insecticidal and repellent properties against several insect species. In our
      research, the essential oil (EO) extracted from fresh leaves of Hyptis suaveolens
      (Lamiaceae), and its main constituents were evaluated for larvicidal and
      repellent activity against the Asian tiger mosquito, Aedes albopictus Skuse
      (Diptera: Culicidae), currently the most invasive mosquito worldwide. H.
      suaveolens EO had insecticidal activity against A. albopictus larvae and
      mortality was dosage dependent. At the highest dosages of 450 and 400 ppm, there
      were no significant differences on larval mortality, as mortality ranged between
      98.33% and 93.33%, respectively. At dosages ranging from 250 to 350 ppm,
      mortality rates were lower and not significantly different from each other.
      Terpinolene was found to be the most effective pure compound. Efficacy protection
      from H. suaveolens EO, at dosages ranging from 0.03748 to 0.7496 MUg cm(-2) of
      skin, was evaluated during 150 min of observation. Results indicated that this EO
      had a significant repellent activity (RD(50) = 0.00035 MUg cm(-2); RD(90) =
      0.00048 MUg cm(-2)), with differences in repellency rates, as a function of both
      concentration and observation time. Protection time ranged from 16 to 135 min.
      These results clearly evidenced that the larvicidal and repellent activity of H.
      suaveolens EO could be used for the development of new and safer products against
      A. albopictus.

PMID- 22160256
TI  - Postpartum anemia II: prevention and treatment.
AB  - This review focuses on the prevention and treatment of anemia in women who have
      just given childbirth (postpartum anemia). The problem of anemia both prepartum
      and postpartum is far more prevalent in developing countries than in the Western
      societies. The conditions for mother and child in the postpartum, nursing, and
      lactation period should be as favorable as possible. Many young mothers have a
      troublesome life due to iron deficiency and iron deficiency anemia (IDA) causing
      a plethora of symptoms including fatigue, physical disability, cognitive
      problems, and psychiatric disorders. Routine screening for postpartum anemia
      should be considered as part of the national maternal health programs. Major
      causes of postpartum anemia are prepartum iron deficiency and IDA in combination
      with excessive blood losses at delivery. Postpartum anemia should be defined as a
      hemoglobin level of <110 g/l at 1 week postpartum and <120 g/l at 8 weeks
      postpartum. Bleeding exceeding normal blood losses of approximately 300 ml may
      lead to rapid depletion of body iron reserves and may, unless treated, elicit
      long-standing iron deficiency and IDA in the postpartum period. The prophylaxis
      of postpartum anemia should begin already in early pregnancy in order to ensure a
      good iron status prior to delivery. The most reliable way to obtain this goal is
      to give prophylactic oral ferrous iron supplements 30-50 mg daily from early
      pregnancy and take obstetric precautions in pregnancies at risk for
      complications. In the treatment of slight-to-moderate postpartum IDA, the first
      choice should be oral ferrous iron 100 to 200 mg daily; it is essential to
      analyze hemoglobin after approximately 2 weeks in order to check whether
      treatment works. In severe IDA, intravenous ferric iron in doses ranging from 800
      to 1,500 mg should be considered as first choice. In a few women with severe
      anemia and blunted erythropoiesis due to infection and/or inflammation,
      additional recombinant human erythropoietin may be considered. Blood transfusion
      should be restricted to women who develop circulatory instability due to
      postpartum hemorrhage. National health authorities should establish guidelines to
      combat iron deficiency in pregnancy and postpartum in order to facilitate a
      prosperous future for both mothers and children in a continuing globalized world.

PMID- 22160257
TI  - Effects of leucine and citrulline versus non-essential amino acids on muscle
      protein synthesis in fasted rat: a common activation pathway?
AB  - Leucine (LEU) is recognized as a major regulator of muscle protein synthesis
      (MPS). Citrulline (CIT) is emerging as a potent new regulator. The aim of our
      study was to compare MPS modulation by CIT and LEU in food-deprived rats and to
      determine whether their action was driven by similar mechanisms. Rats were either
      freely fed (F, n = 10) or food deprived for 18 h. Food-deprived rats were
      randomly assigned to one of four groups and received per os, i.e., gavage, saline
      (S, n = 10), L: -leucine (1.35 g/kg, LEU, n = 10), L: -citrulline (1.80 g/kg CIT,
      n = 10) or isonitrogenous non-essential amino acids (NEAA, n = 10). After gavage,
      the rats were injected with a flooding dose of [(13)C] valine to determine MPS.
      The rats were killed 50 min after the injection of the flooding dose. Blood was
      collected for amino acid, glucose and insulin determinations. Tibialis anterior
      muscles were excised for determination of MPS and for Western blot analyses of
      the PI3K/Akt, mTORC1, ERK1/2/MAPK pathways and AMP kinase component. MPS was
      depressed by 61% in starved rats (Saline vs. Fed, P < 0.05). Administration of
      amino acids (NEAA, LEU or CIT) completely abolished this decrease (NEAA, CIT, LEU
      vs. Fed, NS). Food deprivation affected the phosphorylation status of the mTORC1
      pathway and AMP kinase (Saline vs. Fed, P < 0.05). LEU and CIT administration
      differently stimulated the mTORC1 pathway (LEU > CIT). LEU but not CIT increased
      the phosphorylation of rpS6 at serine 235/236. Our findings clearly demonstrated
      that both CIT and LEU were able to stimulate MPS, but this effect was likely
      related to the nitrogen load. LEU, CIT and NEAA may have different actions on MPS
      in this model as they share different mTORC1 regulation capacities.

PMID- 22160258
TI  - Plant aminoaldehyde dehydrogenases oxidize a wide range of nitrogenous
      heterocyclic aldehydes.
AB  - The metabolic degradation of aldehydes is catalyzed by oxidoreductases from which
      aldehyde dehydrogenases (EC 1.2.1) comprise nonspecific or substrate-specific
      enzymes. The latter subset is represented, e.g., by NAD(+)-dependent
      aminoaldehyde dehydrogenases (AMADHs; EC 1.2.1.19) oxidizing a group of naturally
      occurring omega-aminoaldehydes including polyamine oxidation products.
      Recombinant isoenzymes from pea (PsAMADH1 and 2) and tomato (LeAMADH1 and 2) were
      subjected to kinetic measurements with synthetic aldehydes containing a
      nitrogenous heterocycle such as pyridinecarbaldehydes and their halogenated
      derivatives, (pyridinylmethylamino)-aldehydes, pyridinyl propanals and aldehydes
      derived from purine, 7-deazapurine and pyrimidine to characterize their substrate
      specificity and significance of the resulting data for in vivo reactions. The
      enzymatic production of the corresponding carboxylic acids was analyzed by liquid
      chromatography coupled to electrospray ionization mass spectrometry. Although the
      studied AMADHs are largely homologous and supposed to have a very similar active
      site architecture, significant differences were observed. LeAMADH1 displayed the
      broadest specificity oxidizing almost all compounds followed by PsAMADH2 and 1.
      In contrast, LeAMADH2 accepted only a few compounds as substrates. Pyridinyl
      propanals were converted by all isoenzymes, usually better than
      pyridinecarbaldehydes and aldehydes with fused rings. The K (m) values for the
      best substrates were in the range of 10(-5)-10(-4) M. Nevertheless, the catalytic
      efficiency values (V (max)/K (m)) reached only a very small fraction of that with
      3-aminopropanal (except for LeAMADH1 activity with two pyridine-derived
      compounds). Docking experiments using the crystal structure of PsAMADH2 were
      involved to discuss differences in results with position isomers or alkyl chain
      homologs.

PMID- 22160259
TI  - Recent advances in the development of tissue transglutaminase (TG2) inhibitors.
AB  - Tissue transglutaminase (TG2) is a Ca(2+)-dependent enzyme and probably the most
      ubiquitously expressed member of the mammalian transglutaminase family. TG2 plays
      a number of important roles in a variety of biological processes. Via its
      transamidating function, it is responsible for the cross-linking of proteins by
      forming isopeptide bonds between glutamine and lysine residues. Intracellularly,
      Ca(2+) activation of the enzyme is normally tightly regulated by the binding of
      GTP. However, upregulated levels of TG2 are associated with many disease states
      like celiac sprue, certain types of cancer, fibrosis, cystic fibrosis, multiple
      sclerosis, Alzheimer's, Huntington's and Parkinson's disease. Selective
      inhibitors for TG2 both cell penetrating and non-cell penetrating would therefore
      serve as novel therapeutic tools for the treatment of these disease states.
      Moreover, they would provide useful tools to fully elucidate the cellular
      mechanisms TG2 is involved in and help comprehend how the enzyme is regulated at
      the cellular level. The current paper is intended to give an update on the
      recently discovered classes of TG2 inhibitors along with their structure-activity
      relationships. The biological properties of these derivatives, in terms of both
      activity and selectivity, will also be reported in order to translate their
      potential for future therapeutic developments.

PMID- 22160260
TI  - Relationship between protein folding kinetics and amino acid properties.
AB  - The successful prediction of protein-folding rates based on the sequence
      predicted secondary structure suggests that the folding rates might be predicted
      from sequence alone. To pursue this question, we directly predict the folding
      rates from amino acid sequences, which do not require any information on
      secondary or tertiary structure. Our work achieves 88% correlation with folding
      rates determined experimentally for proteins of all folding types and peptide,
      suggesting that almost all of the information needed to specify a protein's
      folding kinetics and mechanism is comprised within its amino acid sequence. The
      influence of residue on folding rate is related to amino acid properties.
      Hydrophobic character of amino acids may be an important determinant of folding
      kinetics, whereas other properties, size, flexibility, polarity and isoelectric
      point, of amino acids have contributed little to the folding rate constant.

PMID- 22160261
TI  - GABA is an effective immunomodulatory molecule.
AB  - In recent years, it has become clear that there is an extensive cross-talk
      between the nervous and the immune system. Somewhat surprisingly, the immune
      cells themselves do express components of the neuronal neurotransmitters systems.
      What role the neurotransmitters, their ion channels, receptors and transporters
      have in immune function and regulation is an emerging field of study. Several
      recent studies have shown that the immune system is capable of synthesizing and
      releasing the classical neurotransmitter GABA (gamma-aminobutyric acid). GABA has
      a number of effects on the immune cells such as activation or suppression of
      cytokine secretion, modification of cell proliferation and GABA can even affect
      migration of the cells. The immune cells encounter GABA when released by the
      immune cells themselves or when the immune cells enter the brain. In addition,
      GABA can also be found in tissues like the lymph nodes, the islets of Langerhans
      and GABA is in high enough concentration in blood to activate, e.g., GABA-A
      channels. GABA appears to have a role in autoimmune diseases like multiple
      sclerosis, type 1 diabetes, and rheumatoid arthritis and may modulate the immune
      response to infections. In the near future, it will be important to work out what
      specific effects GABA has on the function of the different types of immune cells
      and determine the underlying mechanisms. In this review, we discuss some of the
      recent findings revealing the role of GABA as an immunomodulator.

PMID- 22160262
TI  - Polymorphism of transglutaminase 2: unusually low frequency of genomic variants
      with deficient functions.
AB  - Transglutaminase 2 (TG2) is a multifunctional member of an enzyme family: it
      modifies glutamine residues by cross-linking proteins and incorporating primary
      amines into them, has protein disulphide isomerase and protein kinase activities,
      mediates trans-membrane signal transduction and interactions between cell surface
      proteins and the extracellular matrix. These unusual multiple roles encoded into
      one polypeptide chain suggest that genomic variations in the TGM2 gene should be
      limited. Indeed, the available information in databases shows that unlike in the
      case of most other transglutaminases there are no common single nucleotide
      polymorphisms in exons of human TGM2. We collected data on and produced some of
      the rare genetic variants of TGM2 by site directed mutagenesis and found that
      some were less stable than the most abundant (wild type) enzyme variant and the
      majority had deficient transamidating activity. Further studies are required to
      clarify the pathologic significance of these rare TGM2 alleles in the human
      population.

PMID- 22160263
TI  - Synaptic localisation of agmatinase in rat cerebral cortex revealed by virtual
      pre-embedding.
AB  - Light microscopic evidence suggested a synaptic role for agmatinase, an enzyme
      capable of inactivating the putative neurotransmitter and endogenous anti
      depressant agmatine. Using electron microscopy and an alternative pre-embedding
      approach referred to as virtual pre-embedding, agmatinase was localised pre- and
      postsynaptically, to dendritic spines, spine and non-spine terminals, and
      dendritic profiles. In dendritic spines, labelling displayed a tendency towards
      the postsynaptic density. These results further strengthen a synaptic role for
      agmatine and strongly suggest a regulatory role for synaptically expressed
      agmatinase.

PMID- 22160264
TI  - Homocysteine enhances clot-promoting activity of endothelial cells via
      phosphatidylserine externalization and microparticles formation.
AB  - Total elevated plasma homocysteine (Hcy) is a risk factor for thromboembolism.
      Vascular endothelium is important to regulate coagulation, but the impact of Hcy
      on the clot-promoting activity (CPA) of endothelial cells has not been fully
      understood. In our study, human umbilical vein endothelial cells (HUVECs) were
      treated with Hcy (8, 20, 80, 200, 800 MUmol/L) for 24 h. Annexin V was utilized
      to detect phosphatidylserine (PS) externalization and endothelial microparticles
      (MPs) formation. CPA was assessed by recalcification time and purified clotting
      complex tests. We found that Hcy enhanced the externalized PS and consequent CPA
      of HUVECs in a dose-dependent fashion, effect of Hcy had statistical significance
      at 800 MUmol/L. In addition, Hcy also increased the shedding of procoagulant
      endothelial MPs. Blocking of PS with 128 nmol/L annexin V reduced approximately
      70% CPA of HUVECs and endothelial MPs, but human anti-tissue factor antibody had
      little inhibitive effect. Our results showed that Hcy increased CPA of HUVECs via
      PS externalization and MPs release. Our present study has implications for
      hyperhomocysteinemia-related hypercoagulability.

PMID- 22160265
TI  - Prevention of fibrosis progression in CCl4-treated rats: role of the hepatic
      endocannabinoid and apelin systems.
AB  - Endocannabinoids behave as antifibrogenic agents by interacting with cannabinoid
      CB2 receptors, whereas the apelin (AP) system acts as a proangiogenic and
      profibrogenic mediator in the liver. This study assessed the effect of long-term
      stimulation of CB2 receptors or AP receptor (APJ) blockade on fibrosis
      progression in rats under a non-discontinued fibrosis induction program. The
      study was performed in control and CCl(4)-treated rats for 13 weeks. Fibrosis
      induced rats received a CB2 receptor agonist (R,S)-3-(2-iodo-5-nitrobenzoyl)-1-(1
      methyl-2-piperidinylmethyl)-1H-indole (AM1241) (1 mg/kg b.wt.), an APJ antagonist
      [Ala(13)]-apelin-13 sequence: Gln-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Ala
      (F13A) (75 MUg/kg b.wt.), or vehicle daily during the last 5 weeks of the CCl(4)
      inhalation program. Mean arterial pressure (MAP), portal pressure (PP), hepatic
      collagen content, angiogenesis, cell infiltrate, and mRNA expression of a panel
      of fibrosis-related genes were measured in all animals. Fibrosis-induced rats
      showed increased hepatic collagen content, reduced MAP, portal hypertension, and
      increased expression of the assessed messengers in comparison with control rats.
      However, fibrotic rats treated with either AM1241 or F13A had reduced hepatic
      collagen content, improved MAP and PP, ameliorated cell viability, and reduced
      angiogenesis and cell infiltrate compared with untreated fibrotic rats. These
      results were associated with attenuated induction of platelet-derived growth
      factor receptor beta, alpha-smooth muscle actin, matrix metalloproteinases, and
      tissue inhibitors of matrix metalloproteinase. CB2 receptor stimulation or APJ
      blockade prevents fibrosis progression in CCl(4)-treated rats. The mechanisms
      underlying these phenomena are coincident despite the marked dissimilarities
      between the CB2 and APJ signaling pathways, thus opening new avenues for
      preventing fibrosis progression in liver diseases.

PMID- 22160266
TI  - Antenatal phosphodiesterase 4 inhibition restores postnatal growth and pulmonary
      development in a model of chorioamnionitis in rabbits.
AB  - Chorioamnionitis is implicated in the pathophysiology of bronchopulmonary
      disease, and the associated inflammatory response is responsible for adverse
      effects on alveolar development. The aim of this work was to analyze the effects
      of a phosphodiesterase 4 (PDE4)-selective inhibitor, rolipram (a modulator of the
      inflammatory response), in an experimental model of chorioamnionitis on pulmonary
      development and on the processes of infection and inflammation. Rabbit mothers
      were assigned to four groups: 1) saline serum inoculation (controls); 2)
      Escherichia coli intrauterine inoculation (C+); 3) rolipram infusion (R+); and 4)
      E. coli inoculation + rolipram infusion (C+R+). High rates of morbility and
      mortality were noticed in mothers and pups (5 of 13 pregnant rabbits in groups
      with rolipram). Alveolar development, inflammation, and infection were analyzed
      in pups at day 0 and day 5. At day 0, in the context of chorioamnionitis,
      rolipram significantly decreased birth weight (p < 0.01) relative to that of
      controls (p < 0.05). At day 5, weight normalized in group C+R+ but not in group
      C+ relative to controls (p < 0.001); moreover, alveolar airspace volume was
      preserved in group C+R+ but not in group C+ (p < 0.05). Interstitial volume
      decreased in group C+ versus controls (p < 0.05) but was preserved in group C+R+.
      Specific alveolar area was not significantly modified by rolipram. No significant
      difference was found concerning bronchoalveolar lavage cellularity, and all blood
      cultures remained sterile. In this model of impaired alveologenesis, rolipram
      significantly preserved specific alveolar density. However, PDE4 inhibition
      induced antenatal fetal demise and growth retardation.

PMID- 22160267
TI  - A fibrinogen-derived peptide provides intercellular adhesion molecule-1-specific
      targeting and intraendothelial transport of polymer nanocarriers in human cell
      cultures and mice.
AB  - Intercellular adhesion molecule-1 (ICAM-1), a transmembrane glycoprotein
      expressed on activated endothelium and many other cells, represents a suitable
      target for delivery of drug nanocarriers (NCs) to disease areas. Numerous works
      have shown efficient targeting and intracellular transport of ICAM-1-targeted
      NCs, rendering significant therapeutic potential. This is the case for enzyme
      delivery for treatment of multitissue lysosomal storage disorders. However, those
      studies used formulations targeted to ICAM-1 by antibodies (anti-ICAM NCs). This
      poses an obstacle to preclinical evaluation of long-term treatment of such
      chronic maladies, caused by immunogenicity of foreign proteins administered to
      animals, compelling development of alternative strategies. In this work, we used
      radioisotope tracing, fluorescence and electron microscopy, and in vitro, cell
      cultures, and mouse models to evaluate polymer nanocarriers targeted to ICAM-1 by
      a 17-mer linear peptide derived from the ICAM-1-binding sequence of fibrinogen
      (gamma3). Our results show that gamma3 NCs target ICAM-1 with efficiency and
      specificity similar to that of anti-ICAM NCs, determined by using immobilized
      ICAM-1, native ICAM-1 expressed on endothelial cell cultures, and intravenous
      administration in mice. Furthermore, gamma3 NCs are internalized by cells in
      culture and in vivo and transported to lysosomes via cell adhesion molecule
      mediated endocytosis, without apparent disruption of cell junctions, similar to
      anti-ICAM counterparts. The degree of conservation of fibrinogen gamma3 sequence
      and its cognate site on ICAM-1 among species (e.g., mouse, chimpanzee, and
      humans) reflects the interspecies targeting found for gamma3 NCs, providing an
      avenue for exploring the translation of ICAM-1-targeting platforms in the
      preclinical and, perhaps, future clinical realm.

PMID- 22160268
TI  - Preclinical evaluation of an inhibitor of cytosolic phospholipase A2alpha for the
      treatment of asthma.
AB  - Asthma is a chronic inflammatory lung disease with considerable unmet medical
      needs for new and effective therapies. Cytosolic phospholipase A(2)alpha
      (cPLA(2)alpha) is the rate-limiting enzyme that is ultimately responsible for the
      production of eicosanoids implicated in the pathogenesis of asthma. We
      investigated a novel cPLA(2)alpha inhibitor, PF-5212372, to establish the
      potential of this drug as a treatment for asthma. PF-5212372 was a potent
      inhibitor of cPLA(2)alpha (7 nM) and was able to inhibit prostaglandin (PG)D(2)
      and cysteinyl leukotriene release from anti-IgE-stimulated human lung mast cells
      (0.29 and 0.45 nM, respectively). In a mixed human lung cell population, PF
      5212372 was able to inhibit ionomycin-stimulated release of leukotriene B(4),
      thromboxane A(2), and PGD(2) (2.6, 2.6, and 4.0 nM, respectively) but was
      significantly less effective against PGE(2) release (>301 nM; p < 0.05). In an in
      vitro cell retention assay, PF-5212372 retained its potency up to 24 h after
      being washed off. In a sheep model of allergic inflammation, inhalation of PF
      5212372 significantly inhibited late-phase bronchoconstriction (78% inhibition; p
      < 0.001) and airway hyper-responsiveness (94% inhibition; p < 0.001), and
      isolated sheep lung mast cell assays confirmed species translation via effective
      inhibition of PGD(2) release (0.78 nM). Finally, PF-5212372 was assessed for its
      ability to inhibit the contraction of human bronchi induced by AMP. PF5212372
      significantly inhibited AMP-induced contraction of human bronchi (81% inhibition;
      p < 0.001); this finding, together with the ability of this drug to be effective
      in a wide range of preclinical asthma models, suggests that inhibition of
      cPLA(2)alpha with PF-5212372 may represent a new therapeutic option for the
      treatment of asthma.

PMID- 22160269
TI  - Regulation of tissue-specific expression of renal organic anion transporters by
      hepatocyte nuclear factor 1 alpha/beta and DNA methylation.
AB  - We have reported previously that the kidney- and liver-specific expression of
      transporters in mice involves the coordinated regulation by hepatocyte nuclear
      factor 1 (HNF1) and DNA methylation. The present study was aimed at investigating
      the role of this cascade in the transcriptional regulation of renal organic anion
      transporters (OATs) yet to be characterized in human and mouse. Luciferase assays
      and electrophoretic mobility-shift assays demonstrated that HNF1alpha/beta
      enhances the promoter activity of OAT4/SLC22A11 via binding to the HNF1 motif
      located near the transcriptional start site (TSS). DNA methylation profiles of
      human OAT1, OAT3, OAT4, and urate transporter 1 (URAT1) were determined in human
      liver and kidney cortex by bisulfite sequencing. Most of the CpG dinucleotides
      around the TSSs of OAT1 and OAT3 were highly methylated in the liver compared
      with kidney cortex, being consistent with their tissue specificity, whereas the
      difference in the DNA methylation status was less remarkable between the two
      tissues for OAT4 and URAT1. Mouse Oat1 gene also contained CpG dinucleotides
      hypomethylated in the kidney and hypermethylated in the liver downstream its TSS,
      whereas two of the seven CpG dinucleotides around the TSS of mouse Oat3 were
      significantly methylated in the liver compared with the kidney. Taken together,
      these findings underscored the central role of HNF1alpha/beta in the
      transcriptional regulation of OATs and highlighted DNA methylation-dependent gene
      silencing as one of the mechanisms underlying the tissue-specific transactivation
      by this master regulator.

PMID- 22160270
TI  - The social ecology of adolescent-initiated parent abuse: a review of the
      literature.
AB  - This article provides an ecological framework for understanding adolescent
      initiated parent abuse. We review research on adolescent-initiated parent abuse,
      identifying sociodemographic characteristics of perpetrators and victims (e.g.,
      gender, age, race/ethnicity, and socioeconomic status [SES]). Bronfenbrenner's
      [1] ecological systems theory is applied, which examines the risk and protective
      factors for adolescent-initiated parent abuse within micro- (maltreatment,
      domestic violence, parenting behavior and disciplinary strategies), meso- (peer
      influence), exo- (media influence), macro- (gender role socialization), and
      chronosystem (change in family structure) levels. Findings from our review
      suggest that older and White children are significantly more likely to abuse
      their parents. Females are selective in the target of their aggression, while
      males target family members in general. Mothers are significantly more likely to
      be abused than fathers. However, researchers also report variations in the
      association between SES and parent abuse. Domestic violence and child
      maltreatment are risk factors, while findings on parenting behavior and
      disciplinary strategies are mixed. Peer influence, exposure to media violence,
      gender role socialization, and change in family structure can potentially
      increase the risk of parent abuse. Practice and research implications are also
      discussed. An ecological systems framework allows for an examination of how
      various contexts interact and influence parent abuse behavior, and can provide
      needed directions for further research.

PMID- 22160271
TI  - Emotion regulation and depressive symptoms in preadolescence.
AB  - This study examined associations among several measures of emotion regulation,
      and their links to depressive symptoms, in a sample of children ages 10-12 years
      old (N=87). Both temporal features of emotion regulation and regulation processes
      involved in the evaluation, monitoring, and modification of emotion were assessed
      through parent and child report and behavioral observation. Children also
      completed a self-report measure of depressive symptoms. Children with more
      depressive symptoms were reported by mothers and rated by observers as having
      higher levels of negative affect intensity. Regarding emotion regulation
      processes, children with more depressive symptoms reported more biased
      interpretations of emotionally charged situations, less awareness of their
      emotions, and their mothers reported that they utilized less problem-focused
      coping and positive reframing when coping with upsetting events. Findings suggest
      that children with depressive symptoms experience a wide range of difficulties
      with emotion regulation.

PMID- 22160274
TI  - Impact of chronic atrial fibrillation in patients with severe heart failure and
      indication for CRT: data of two registries with 711 patients (1999-2006 and 2007
      6/2008).
AB  - AIMS: Atrial fibrillation (AF) is a relevant comorbidity in heart failure (HF)
      patients. In milestone cardiac resynchronization therapy (CRT) studies, patients
      with AF were excluded. We sought to investigate the influence of chronic atrial
      fibrillation (AF) on patients with CRT. AV node (AVN) ablation is frequently
      recommended. Converting AF to sinus rhythm (SR) is not a standard concept.
      METHODS: A total of 584 consecutive patients with CRT devices were included in a
      single-center registry from 1999-2006 (retrospective registry) and 127/324
      patients from 2007-06/2008 (prospective registry). The impact of persistent AF
      (group 1) on clinical and echocardiographic improvement compared with patients in
      SR (group 2) after 12 (6) months follow-up were analyzed. Re-establishing SR
      after initial cardioversion or need for AVN ablation was examined. RESULTS: In
      the retrospective registry, 139 (24%) patients presented with AF (group 1) and
      445 with SR (group 2). The groups differed in age, gender, and left atrium (LA)
      size but not in NYHA class, ejection fraction (EF), left ventricular end
      diastolic dimension (LVEDD), B-type natriuretic peptide (BNP) levels, QRS width,
      and underlying disease. After 1 year, CRT improvement of NYHA class and EF was
      similar with higher mortality in group 1 (12% vs. 7%; OR 1.80; 95% confidence
      interval 0.95-3.4). The AF group presented with SR in 33/82 (40%) patients and
      11% needed AVN ablation. The prospective data showed 27 (21%) patients in AF with
      conversion to SR in 41% after 6 months. CONCLUSION: Patients with severe HF and
      chronic AF had a comparable improvement with CRT as those in SR. CRT is a
      successful treatment option in patients with chronic AF offering the potential to
      restore SR in a significant number of patients.

PMID- 22160273
TI  - Influence of growth manner on nitrifying bacterial communities and nitrification
      kinetics in three lab-scale bioreactors.
AB  - The effects of growth type, including attached growth, suspended growth, and
      combined growth, on the characteristics of communities of ammonia-oxidizing
      bacteria (AOB) and nitrite-oxidizing bacteria (NOB) were studied in three lab
      scale Anaerobic/Anoxic(m)-Oxic(n) (AmOn) systems. These systems amplified
      activated sludge, biofilms, and a mixture of activated sludge and biofilm (AS
      BF). Identical inocula were adopted to analyze the selective effects of mixed
      growth patterns on nitrifying bacteria. Fluctuations in the concentration of
      nitrifying bacteria over the 120 days of system operation were analyzed, as was
      the composition of nitrifying bacterial community in the stabilized stage.
      Analysis was conducted using polymerase chain reaction-denaturing gradient gel
      electrophoresis (PCR-DGGE) and real-time PCR. According to the DGGE patterns, the
      primary AOB lineages were Nitrosomonas europaea (six sequences), Nitrosomonas
      oligotropha (two sequences), and Nitrosospira (one sequence). The primary
      subclass of NOB community was Nitrospira, in which all identified sequences
      belonged to Nitrospira moscoviensis (14 sequences). Nitrobacter consisted of two
      lineages, namely Nitrobacter vulgaris (three sequences) and Nitrobacter alkalicus
      (two sequences). Under identical operating conditions, the composition of
      nitrifying bacterial communities in the AS-BF system demonstrated significant
      differences from those in the activated sludge system and those in the biofilm
      system. Major varieties included several new, dominant bacterial sequences in the
      AS-BF system, such as N. europaea and Nitrosospira and a higher concentration of
      AOB relative to the activated sludge system. However, no similar differences were
      discovered for the concentration of the NOB population. A kinetic study of
      nitrification demonstrated a higher maximum specific growth rate of mixed sludge
      and a lower half-saturation constant of mixed biofilm, indicating that the AS-BF
      system maintained relatively good nitrifying ability.

PMID- 22160275
TI  - Outcome of laser-assisted laparoscopic partial nephrectomy without ischaemia for
      peripheral renal tumours.
AB  - OBJECTIVES: Evaluation of clamp-off laser-assisted laparoscopic partial
      nephrectomy technique (LLPN) compared to the clamp-off laparoscopic (LPN) and
      open (OPN) techniques. PATIENTS AND METHODS: Between September 2008 and July
      2011, 36 patients suffering from small peripheral renal tumours (RT) underwent
      LLPN (n = 12), LPN (n = 12) and OPN (n = 12) in a prospective single-centre
      study. RT were excised with laser, Sonosurg or monopolar scissors during LLPN,
      LPN and OPN, respectively. Blood vessels are identified and sutured before
      opening them; alternatively, laser energy was used to coagulate them (LLPN).
      Early and late postoperative complications were assessed. Follow-up was done
      according to EAU-guidelines. RESULTS: Mean age was 64.9 years. Mean operative
      time was 135.8 min (100-180) versus 144.2 (85-255) versus 113.6 (50-170) for LLPN
      versus LPN versus OPN, respectively. Median estimated blood loss (EBL) was 170.8
      ml (50-600) versus 245.2 (50-700) versus 425.8 (100-900) for LLPN versus LPN
      versus OPN, respectively. Tumours (19 right and 17 left) were located in upper
      (11), midparenchyma (13) and lower pole (12). Mean tumour size was 2.7 cm (1.2
      5.5). There were no reported perioperative complications/conversions. There were
      no positive margins. Histological evaluations were not compromised in any LLPN
      case. Compared to LPN, LLPN offered significant lower EBL, shorter operative
      time, otherwise, comparable results. Follow-up was uneventful without tumour
      recurrences. CONCLUSION: Current prospective comparative study shows that LLPN is
      a reproducible efficient alternative to LPN/OPN. Besides the absence of renal
      ischaemia, LLPN offered lower EBL, good haemostasis and minimal parenchyma
      damage. Surgical and oncological outcomes are comparable to LPN and OPN.

PMID- 22160272
TI  - Role of peroxisomes in the biosynthesis and secretion of beta-lactams and other
      secondary metabolites.
AB  - Peroxisomes are eukaryotic organelles surrounded by a single bilayer membrane,
      containing a variety of proteins depending on the organism; they mainly perform
      degradation reactions of toxic metabolites (detoxification), catabolism of linear
      and branched-chain fatty acids, and removal of H(2)O(2) (formed in some oxidative
      processes) by catalase. Proteins named peroxins are involved in recruiting,
      transporting, and introducing the peroxisomal matrix proteins into the
      peroxisomes. The matrix proteins contain the peroxisomal targeting signals PTS1
      and/or PTS2 that are recognized by the peroxins Pex5 and Pex7, respectively.
      Initial evidence indicated that the penicillin biosynthetic enzyme isopenicillin
      N acyltransferase (IAT) of Penicillium chrysogenum is located inside peroxisomes.
      There is now solid evidence (based on electron microscopy and/or biochemical
      data) confirming that IAT and the phenylacetic acid- and fatty acid-activating
      enzymes are also located in peroxisomes. Similarly, the Acremonium chrysogenum
      CefD1 and CefD2 proteins that perform the central reactions (activation and
      epimerization of isopenicillin N) of the cephalosporin pathway are targeted to
      peroxisomes. Growing evidence supports the conclusion that some enzymes involved
      in the biosynthesis of mycotoxins (e.g., AK-toxin), and the biosynthesis of
      signaling molecules in plants (e.g., jasmonic acid or auxins) occur in
      peroxisomes. The high concentration of substrates (in many cases toxic to the
      cytoplasm) and enzymes inside the peroxisomes allows efficient synthesis of
      metabolites with interesting biological or pharmacological activities. This
      compartmentalization poses additional challenges to the cell due to the need to
      import the substrates into the peroxisomes and to export the final products; the
      transporters involved in these processes are still very poorly known. This
      article focuses on new aspects of the metabolic processes occurring in
      peroxisomes, namely the degradation and detoxification processes that lead to the
      biosynthesis and secretion of secondary metabolites.

PMID- 22160276
TI  - Screening pediatric delirium with an adapted version of the Sophia Observation
      withdrawal Symptoms scale (SOS).

PMID- 22160277
TI  - Declining rates of hepatocellular carcinoma in urban Shanghai: incidence trends
      in 1976-2005.
AB  - In China, hepatocellular carcinoma (HCC) incidence rates in several registry
      catchment populations are amongst the highest worldwide. The incidence rates in
      urban Shanghai were analyzed between 1976 and 2005 to describe and interpret the
      time trends. Age-specific and age-standardized rates were calculated and
      graphically presented. An age-period-cohort model was fitted to assess the
      effects of age at diagnosis, calendar period, and birth cohort on the changing
      HCC incidence rates. In total, 35,241 and 13,931 men and women were diagnosed
      with HCC during 1976-2005 in urban Shanghai. The age-standardized incidence rates
      in urban Shanghai were 33.9 per 10(5) among men and 11.4 per 10(5) among women in
      1976-1980, but decreased in both sexes to 25.8 per 10(5) and 8.5 per 10(5),
      respectively by 2001-2005. Accelerating rates in birth cohorts born in the early
      1930s and decelerating rates circa 1945 were observed in both sexes, with further
      accelerations noted in the late-1950s (in women) and early-1960s (in men). Given
      the parameterization, increases in risk of HCC were seen in successive male and
      female generations between 1900 and 1935, followed by a further increase among
      successive cohorts born around 1960, with a reduction in risk in the most recent
      generations. The incidence rates of HCC in urban Shanghai from 1976 to 2005 have
      declined in both sexes, with the complex but similar patterns observed in
      successive generations suggestive of a shared changing prevalence in risk factors
      in men and women, with a role possibly for HBV interventions reducing risk of HCC
      in cohorts born after 1960.

PMID- 22160278
TI  - Leishmania major protein disulfide isomerase as a drug target: enzymatic and
      functional characterization.
AB  - Leishmaniasis is a major health problem worldwide and tools available for their
      control are limited. Effective vaccines are still lacking, drugs are toxic and
      expensive, and parasites develop resistance to chemotherapy. In this context, new
      antimicrobials are urgently needed to control the disease in both human and
      animal. Here, we report the enzymatic and functional characterization of a
      Leishmania virulence factor, Leishmania major Protein disulfide isomerase (LmPDI)
      that could constitute a potential drug target. LmPDI possesses domain structure
      organization similar to other PDI family members (a, a', b, b' and c domains),
      and it displays the three enzymatic and functional activities specific of PDI
      family members: isomerase, reductase and chaperone. These results suggest that
      LmPDI plays a key role in assisting Leishmania protein folding via its capacity
      to catalyze formation, breakage, and rearrangement of disulfide bonds in nascent
      polypeptides. Moreover, Bacitracin, a reductase activity inhibitor, and
      Ribostamycin, a chaperone activity inhibitor, were tested in LmPDI enzymatic
      assays and versus Leishmania promastigote in vitro cultures and Leishmania
      amastigote multiplication inside infected THP-1-derived macrophages. Bacitracin
      inhibited both isomerase and reductase activities, while Ribostamycin had no
      effect on the chaperone activity. Interestingly, Bacitracin blocked in vitro
      promastigote growth as well as amastigote multiplication inside macrophages with
      EC(50) values of 39 MUM. These results suggest that LmPDI may constitute an
      interesting target for the development of new anti-Leishmania drugs.

PMID- 22160279
TI  - Increased expression of TLR-2, COX-2, and SOD-2 genes in the peripheral blood
      leukocytes of opisthorchiasis patients induced by Opisthorchis viverrini antigen.
AB  - Re-infection with liver fluke, Opisthorchis viverrini, increases proinflammatory
      molecules involved in inflammation-mediated disease and carcinogenesis in an
      animal model. To clarify whether these genes respond to parasite antigen in
      peripheral blood leukocytes (PBL) of opisthorchiasis patients, we examined the
      transcriptional level of oxidant-generating (toll-like receptor 2 (TLR-2),
      nuclear factor-kappa B (NF-KB), and cyclooxygenase 2 (COX-2)), anti-oxidant
      generating (manganese superoxide dismutase 2 (SOD-2) and catalase (CAT)),
      proinflammatory cytokine (interleukin (IL)-1beta), and anti-inflammatory cytokine
      (IL-10), in PBL exposed to parasite antigen in O. viverrini-infected patients
      compared with healthy individuals in an in vitro experiment. After O. viverrini
      antigen-treated PBL, quantitative RT-PCR analysis revealed that increased
      expression of cytokines and oxidant-generating genes in PBL was similar between
      O. viverrini-infected and healthy groups. Interestingly, compared with healthy
      subjects, increase of TLR-2, COX-2, and SOD-2 and decreased CAT mRNA expression
      levels were observed in O. viverrini-infected group. The results indicate that O.
      viverrini antigen induces upregulation of TLR-2, COX-2, and SOD-2 and
      downregulation of CAT genes in opisthorchiasis patients, suggesting that
      imbalance of oxidant/anti-oxidant transcripts during re-infection may be involved
      in the inflammatory-driven carcinogenesis. These molecules may be used as the
      chemopreventive target for intervention of opisthorchiasis patients in an endemic
      area.

PMID- 22160280
TI  - In vitro amoebicidal activities of Satureja cuneifolia and Melissa officinalis on
      Acanthamoeba castellanii cysts and trophozoites.
AB  - Amoebic keratitis is difficult to treat without total efficacy in some patients
      because of cysts, which are less susceptible than trophozoites to the usual
      treatments. The aim of this study is to evaluate the in vitro amoebicidal
      activity of the methanolic extracts of Satureja cuneifolia and Melissa
      officinalis. In the presence of methanolic extracts (ranging from 1.0 to 32.0
      mg/ml), numbers of the viable Acanthamoe castellanii trophozoites and cysts were
      decreased during the experimental process. Both extracts showed a time- and dose
      dependent amoebicidal action on the trophozoites and cysts. Among the extracts
      tested, S. cuneifolia showed the strongest amoebicidal effect on the trophozoites
      and cysts. In the presence of 32 mg/ml extract, no viable trophozoites were
      observed within 24 h. At the same concentration value, the extract was found
      effective against the cysts at a rate of 46.3% within 72 h of the experimental
      process. At 16 mg/ml extract concentration, no viable trophozoites were also
      observed in the 24th hour of the experiment. At the end of the experimental
      process, 34.7% of the cysts were killed by the extract. M. officinalis showed
      moderate amoebicidal effect. At the concentration of 32 mg/ml, 44.3% and 30.0% of
      the trophozoites and cysts were killed by the extract, respectively. Results
      obtained from these concentration values were found statistically different in
      terms of their actions both on trophozoites and cysts (p<0.05).

PMID- 22160281
TI  - Fish as a possible reservoir for zoonotic Giardia duodenalis assemblages.
AB  - Giardiasis is a re-emerging infectious disease of worldwide significance caused
      by Giardia duodenalis. This study investigated the occurrence of zoonotic G.
      duodenalis assemblages in fish to explore the possible role of fish in the
      epidemiology of human giardiasis. For this purpose, 92 fish (Tilapia nilotica and
      Mugil cephalus) collected from (fish farms and Nile River) at different
      governorates in Egypt were examined for the presence of G. duodenalis in their
      feces by using enzyme linked immunosorbent assay, then positive fecal samples
      were tested by duplex PCR for identification of triose phosphate isomerase (tpi)
      gene specific for zoonotic assemblages A and B. The overall prevalence of G.
      duodenalis in the examined fish was 3.3%, while the detection rates among the
      examined fish species were 2.9% and 4.2% for T. nilotica and M. cephalus,
      respectively. G. duodenalis was detected in the feces of both farmed and wild
      fish whereas all isolates were genotyped as assemblage A. In conclusion, the
      occurrence of zoonotic G. duodenalis assemblage A in the examined fish species at
      two different aquatic environments underlines the possibility of fish to be an
      additional reservoir for zoonotic G. duodenalis assemblages that contributes in
      the contamination of water with this pathogen and thus the role of fish in the
      epidemiology of human giardiasis cannot be ruled out.

PMID- 22160283
TI  - Imaging the pregnant patient with abdominal pain.
AB  - Imaging of pregnant patients with non-obstetric abdominal pain is reviewed, with
      an accompanying pictorial essay of cases with concentration on magnetic resonance
      imaging. Non-obstetric causes of abdominal pain during pregnancy are similar to
      those of non-pregnant patients. The most common causes are appendicitis and
      cholecystitis. Other causes are myriad and include biliary, gastrointestinal,
      infectious, inflammatory, and malignant etiologies, among others. The approach to
      imaging in pregnant patient is unique, as it is imperative to minimize
      potentially harmful radiation exposures to the fetus. Ultrasound and MRI are the
      primary modalities for evaluation of the pregnant patient with abdominal pain.
      The use of intravenous contrast is discouraged, except in highly-selected
      patients where there is no other way to obtain vital diagnostic information. CT
      is still used as the mainstay of evaluation of blunt abdominal trauma and is
      commonly used for diagnosis of small bowel obstruction, stone disease, and work
      up of malignancy during pregnancy. A discussion of test selection and underlying
      rationale is presented.

PMID- 22160282
TI  - Single session removal of forgotten encrusted ureteral stents: combined
      endourological approach.
AB  - Forgotten ureteral stents represent a difficult problem for urologists; the major
      complications are infection, migration, encrustation, stone formation, and
      multifractured stent, and a consensus on the best therapeutic approach is
      lacking. Here we present our experience with endoscopic management of this
      challenging problem and discuss the various endourological approaches for
      treating forgotten encrusted ureteral stents. From January 2005 to December 2010,
      19 patients (11 women and 8 men) with encrusted ureteral stents were
      retrospectively analyzed. Combined endourologic therapies including
      extracorporeal shock wave lithotripsy (SWL), percutaneous nephrolithotomy (PCNL),
      ureterorenoscopic lithotripsy (URSL), and cystolithotripsy (CLT) were used to
      achieve stent removal. A total of 19 patients with encrusted ureteral stents were
      treated at our center. The mean patient age was 46.2 +/- 18.5 years (8-81), the
      average indwelling time of the stent was 24.7 +/- 19.0 months (8-93), and the
      mean hospital stay was 3.4 +/- 4.0 days (range 1-15 days). Using the described
      combination of techniques, all stents and the associated stones were eventually
      removed without any complications and patients were rendered stone- and stent
      free. A main element of the treatment strategy was to keep the number of
      interventions as low as possible. The use of various combinations of
      endourological techniques can achieve effective stent and stone treatment after a
      single anesthesia session with minimal morbidity and short hospital stay.

PMID- 22160284
TI  - Intrapancreatic accessory spleen: CT appearance and differential diagnosis.
AB  - Although autopsy studies report that the second most common site of the accessory
      spleen is in the tail of the pancreas, intrapancreatic accessory spleens (IPASs)
      are rarely recognized radiologically. With recent improvements in imaging
      techniques, IPASs are more commonly detected on imaging studies. IPAS can be
      mistaken for other type of mass-forming lesions in the tail of the pancreas,
      particularly an asymptomatic small neuroendocrine neoplasm. Rarely, an epidermoid
      cyst originating from IPAS may simulate other cystic pancreatic lesion. Accurate
      preoperative diagnosis would obviate unnecessary surgery. IPAS should be
      considered when a hypervascular mass is seen in the tail of the pancreas on CT.
      Typical location, similar attenuation of the lesion to the spleen on noncontrast,
      and postcontrast CT at different phases are helpful to make diagnosis of IPAS. In
      particular, characteristic heterogeneous contrast enhancement of IPAS on the
      arterial phase may be helpful for correct diagnosis. However, when it remains
      difficult to exclude the other diagnosis, (99m)Tc labeled heat-damaged red blood
      cell scintigraphy or superparamagnetic iron oxide-enhanced MRI can be used to
      confirm the diagnosis of IPAS.

PMID- 22160285
TI  - Adrenergic modulation of immune cells: an update.
AB  - Sympathoadrenergic pathways are crucial to the communication between the nervous
      system and the immune system. The present review addresses emerging issues in the
      adrenergic modulation of immune cells, including: the specific pattern of
      adrenoceptor expression on immune cells and their role and changes upon cell
      differentiation and activation; the production and utilization of noradrenaline
      and adrenaline by immune cells themselves; the dysregulation of adrenergic immune
      mechanisms in disease and their potential as novel therapeutic targets. A wide
      array of sympathoadrenergic therapeutics is currently used for non-immune
      indications, and could represent an attractive source of non-conventional
      immunomodulating agents.

PMID- 22160286
TI  - Magic-angle spinning: a historical perspective.

PMID- 22160287
TI  - New horizons for magic-angle spinning NMR.
AB  - Recent developments in sample rotation technology have had a profound impact on
      magic-angle-spinning NMR. First, rotation frequencies approaching, and even
      exceeding, strong homonuclear spin interactions have made high-resolution solid
      state (1)H spectroscopy much more accessible. Second, the new concept of fast
      rotation sweep spectroscopy has emerged. Third, high-resolution NMR at cryogenic
      temperatures has become feasible, offering an enormous sensitivity gain and the
      opportunity to study a wide range of physical phenomena.

PMID- 22160288
TI  - Strategies for high-resolution proton spectroscopy in solid-state NMR.
AB  - We describe radiofrequency (RF) pulse schemes in solid-state NMR applied to
      samples rotating at the magic angle (MAS) to obtain high-resolution (1)H spectra.
      Without combined RF schemes and MAS, (1)H spectra are normally severely broadened
      by the strong homonuclear proton-proton dipolar couplings. This review gives an
      outline of a representative class of multiple-pulse sequences, designed to work
      with and without MAS, and commonly used for high-resolution proton spectroscopy
      in solid-state NMR. We give a theoretical treatment of these sequences based on
      Floquet theory, both single-mode and bimodal. Using this approach, we define
      first-order homonuclear decoupling efficiency parameters which provide the line
      narrowing characteristics of the various pulse sequences when applied to fast
      rotating samples. These parameters are used to compare the line-narrowing
      efficiencies of the multiple-pulse schemes.

PMID- 22160289
TI  - High-resolution solid-state NMR studies of inclusion complexes.
AB  - New applications of 1D and 2D solid state (SS) NMR spectroscopy in structural
      studies of inclusion complexes (ICs) formed by organic host lattices
      (cyclodextrins, calixarenes, cyclophosphazenes, and fullerenes) are described.
      Each section of the review gives short characteristics of host molecules and
      recent applications of SS NMR. Less common systems, which are interesting as
      models for SS NMR studies, (bis[6-O,6-O'-(1,2;3,4-diisopropylidene-alpha-D
      galactopyranosyl) thiophosphoryl] disulfide (DGTD) and 1,2-dichloro-ethane/tris(5
      acetyl-3-thienyl) methane (TATM)), are also discussed.

PMID- 22160290
TI  - Progress in multiple-quantum magic-angle spinning NMR spectroscopy.
AB  - Recent advances in nuclear magnetic resonance spectroscopy of quadrupolar (I>1/2)
      nuclei with half-integer spins in solids have been reviewed. The advent of
      multiple-quantum (MQ) magic-angle spinning (MAS) spectroscopy gave new momentum
      to the study of quadrupolar nuclei in materials of academic and industrial
      interest such as minerals, ceramics and glasses, microporous and mesoporous
      solids and biological materials. It is now possible to record high-resolution
      solid-state NMR spectra of a range of important nuclei, namely (11)B, (17)O,
      (23)Na, (27)Al, (71)Ga, (91)Nb. Since its introduction in 1995 MQMAS NMR has
      evolved considerably and, at present, a range of very useful related techniques
      are available and have been reviewed, in particular satellite transition (ST)
      MAS, Inverse-STMAS NMR, fast amplitude modulation, and techniques based on the
      dipolar interactions between quadrupolar and spin-1/2 nuclei, such as cross
      polarization MQMAS and MQ heteronuclear correlation spectroscopy (HETCOR) and the
      recently introduced J-coupling based experiments (such as J-HMQC).

PMID- 22160291
TI  - Dipolar solid state NMR approaches towards medium-range structure in oxide
      glasses.
AB  - Modern solid state nuclear magnetic resonance presents new powerful opportunities
      for the elucidation of medium range order in glasses in the sub-nanometer region.
      In contrast to standard chemical shift spectroscopy, the strategy presented here
      is based on the precise measurement and quantitative analysis of internuclear
      magnetic dipole-dipole interactions, which can be related to distance information
      in a straightforward manner. The review discusses the most commonly employed
      experimental techniques, producing dipolar coupling information in both homo- and
      heteronuclear spin systems. The approach is particularly powerful in combination
      with magic-angle sample spinning, producing site-resolved dipolar coupling
      information. We present new applications to oxide-based network glasses,
      permitting network connectivities and spatial cation distributions to be
      elucidated.

PMID- 22160292
TI  - Solid-state NMR studies of bone.
AB  - Solid-state NMR studies on bone, bone mineral standards and collagen are
      reviewed. NMR spectroscopy was mostly applied to the bone mineral and confirmed
      that the structure resembles that of calcium carbonatoapatite of type B. Apatite
      in bone was found to be deficient in structural hydroxyl groups. Concentration
      and distribution of hydrogenphosphate and carbonate ions, and of water in apatite
      crystals (interior vs surface and crystal defects vs structural positions) were
      closely investigated. The NMR characterization of the organic matrix still
      remains a challenge for future research.

PMID- 22160293
TI  - Natural Abundance (15)N and (13)C CP/MAS NMR of Dialkyldithiocarbamate Compounds
      with Ni(II) and Zn(II).
AB  - Different symmetrically substituted and cyclic dialkydithiocarbamate (R=CH(3),
      C(2)H(5), C(3)H(7), i-C(3)H(7), C(4)H(9), i-C(4)H(9) and R(2)=(CH(2))(5),
      (CH(2))(6), (CH(2))(4)O) compounds, such as tetraalkylthiuram disulfides,
      mononuclear nickel(II), binuclear zinc(II) and heteropolynuclear complexes and
      their adducts (both non-solvated and solvated forms) with planar and non-planar N
      donor organic bases, have been prepared and studied by means of natural abundance
      (13)C and (15)N CP/MAS NMR spectroscopy. Useful correlations between molecular
      structures and (13)C and (15)N chemical shifts in these compounds have been
      established and assignments to carbon and nitrogen sites in resolved molecular
      structures have been suggested. A combination of the mesomeric effect of
      dithiocarbamate groups and the (+)inductive effect of alkyl substituents at the
      nitrogen atoms has been discussed in interpretations of (13)C and (15)N chemical
      shifts of the studied compounds. A high sensitivity of (15)N chemical shift to
      the subtle structural differences of both dithiocarbamate groups and N-donor
      molecules has been revealed. Several remarkable cases of conformational isomerism
      have been recognized for both dithiocarbamate complexes and their adducts.

PMID- 22160294
TI  - Age estimation based on a combined arteriosclerotic index.
AB  - This study introduces a new quantity, the combined arteriosclerotic index (CAI),
      which is defined as the ratio between the diameter and the longitudinal prestrain
      of an artery. The longitudinal prestrain has been adopted as the ratio between
      the in situ length and the excised length of the abdominal aorta, and is a
      measure of arterial elasticity. During ageing, arteriosclerosis is manifested by
      the loss of pretension and by enlargement of the diameter of the artery. CAI
      combines these two effects. A sample of 61 female and 194 male autopsy
      measurements of human abdominal aortas shows that CAI correlates significantly
      with chronological age (R = 0.916/0.921; female/male). The sample had the
      following parameters: age 53 +/- 19/48 +/- 16 years; diameter of the abdominal
      aorta 12.4 +/- 2.2/13.4 +/- 2.1 mm; and longitudinal prestrain 1.13 +/- 0.10/1.15
      +/- 0.10 (mean +/- sample standard deviation; female/male). The resulting CAI was
      11.2 +/- 2.7/11.9 +/- 2.6 mm. The classical linear regression model was employed
      for age estimation by CAI. The model gave a residual standard deviation of
      7.6/6.3 years and a 95% prediction interval range of  +/- 15.4/12.5 years
      (female/male). A two-sample t-test confirmed that there are significant
      differences between the female and male population during ageing, reflected by
      CAI, unlike longitudinal prestrain. It was concluded that CAI is a suitable
      predictor of age at time of death and is easily obtainable in the autopsy room.

PMID- 22160295
TI  - Examining the feasibility of bulk commodity production in Escherichia coli.
AB  - Escherichia coli is currently used by many research institutions and companies
      around the world as a platform organism for the development of bio-based
      production processes for bulk biochemicals. A given bulk biochemical bioprocess
      must be economically competitive with current production routes. Ideally the
      viability of each bioprocess should be evaluated prior to commencing research,
      both by metabolic network analysis (to determine the maximum theoretical yield of
      a given biocatalyst) and by techno-economic analysis (TEA; to determine the
      conditions required to make the bioprocess cost-competitive). However, these
      steps are rarely performed. Here we examine theoretical yields and review
      available TEA for bulk biochemical production in E. coli. In addition, we examine
      fermentation feedstocks and review recent strain engineering approaches to
      achieve industrially-relevant production, using examples for which TEA has been
      performed: ethanol, poly-3-hydroxybutyrate, and 1,3-propanediol.

PMID- 22160296
TI  - Increase in pectin deposition by overexpression of an ERF gene in cultured cells
      of Arabidopsis thaliana.
AB  - Ethylene-responsive transcription factor (ERF) family genes, which are involved
      in regulation of metabolic pathways and/or are useful for metabolic engineering,
      were investigated in the cultured cells of Arabidopsis thaliana. The pectin
      content in the gelatinous precipitates after the ethanol precipitation of
      extracts derived from calli of a transgenic cell line, A17, overexpressing an ERF
      gene (At1g44830), increased in comparison with the control. Expression of genes
      involved in pectin biosynthesis was up-regulated in the A17 calli. Overexpression
      of the ERF gene coordinately activates the pectin biosynthetic pathway genes and
      increases the content of pectin. These results therefore will be useful as a
      genetic resource for engineering pectin biosynthesis in plants.

PMID- 22160297
TI  - The potential value of bursectomy in operations for trans-serosal gastric
      adenocarcinoma.

PMID- 22160298
TI  - A phase I dose-escalation and pharmacokinetic study of enzastaurin and erlotinib
      in patients with advanced solid tumors.
AB  - PURPOSE: Enzastaurin, an oral serine/threonine kinase inhibitor, targets the
      protein kinase C and AKT pathways with anti-tumor and anti-angiogenic effects.
      Erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has
      activity in solid tumors. Based on the promising combination of EGFR inhibitors
      and anti-angiogenic agents, this phase I trial was initiated. METHODS: This
      single-institution, open-label, non-randomized trial used a standard 3 + 3 dose
      escalation model in patients with advanced solid malignancies including non-small
      cell lung cancer (NSCLC). Two dose levels of enzastaurin (with loading doses)
      were explored: 250 mg daily and 500 mg daily. Erlotinib was given at 150 mg
      daily. RESULTS: Sixteen patients were enrolled in this study (median age, 64
      years). Most patients were heavily pre-treated, female, and Caucasian and had
      NSCLC. The highest dose of enzastaurin, 500 mg daily, was tolerated with no
      unexpected adverse events and no alteration in the pharmacokinetics of either
      drug at this dose level. The mean clearance was 5.75 L/h for erlotinib and 53.8
      L/h for enzastaurin. The most common possibly drug-related grade 3-4 adverse
      events included diarrhea (25.0%), neurologic symptoms (18.8%), and vomiting
      (18.8%). Activity was noted, with a partial response in one patient and prolonged
      disease stability for >12 cycles in three patients. CONCLUSION: The combination
      of enzastaurin 500 mg daily and erlotinib 150 mg daily is well tolerated and does
      not alter the pharmacokinetics of the individual drugs, with clinical activity
      seen. A phase II trial of this combination has been initiated in patients with
      advanced-stage NSCLC.

PMID- 22160299
TI  - Patterns of contact with hospital for children with an autism spectrum disorder:
      a Danish register-based study.
AB  - The aim of this study was to study patterns of contact with hospital for children
      with autism spectrum disorder (ASD) using Danish population based register data.
      We included all children born in Denmark from 1994 through 2002. We found that
      children diagnosed with ASD had an increased rate of contact with hospital,
      almost regardless of the cause for the hospital contact. Given the overall
      association between hospital contact for various causes and ASD observed in these
      data, hospital data should be used cautiously in future studies searching for
      associations between a specific disease and ASD. If the increased rate of
      hospital contact overall for children with ASD is not considered, then misleading
      over interpretations might be made of observed associations between specific
      diseases and ASD.

PMID- 22160300
TI  - Melatonin for sleep in children with autism: a controlled trial examining dose,
      tolerability, and outcomes.
AB  - Supplemental melatonin has shown promise in treating sleep onset insomnia in
      children with autism spectrum disorders (ASD). Twenty-four children, free of
      psychotropic medications, completed an open-label dose-escalation study to assess
      dose-response, tolerability, safety, feasibility of collecting actigraphy data,
      and ability of outcome measures to detect change during a 14-week intervention.
      Supplemental melatonin improved sleep latency, as measured by actigraphy, in most
      children at 1 or 3 mg dosages. It was effective in week 1 of treatment,
      maintained effects over several months, was well tolerated and safe, and showed
      improvement in sleep, behavior, and parenting stress. Our findings contribute to
      the growing literature on supplemental melatonin for insomnia in ASD and inform
      planning for a large randomized trial in this population.

PMID- 22160301
TI  - Relationships between youth and caregiver strengths and mental health outcomes in
      community based public mental health services.
AB  - To examine relationships between youth and caregiver strengths and behavioral
      health outcomes for youth in community service settings. Strengths and behavioral
      health needs of youth (N = 793) receiving Home and Community Based Services
      Waiver from 2002-2008 were characterized using the child and adolescent needs and
      strengths mental health assessment. Comparisons of assessment scores at admission
      and program completion were conducted using Chi-square, repeated measures ANOVA
      and Cohen's d effect size. Associations between strengths at admission and having
      behavioral health needs met were examined using multivariable logistic
      regression. Youth had high levels of needs on mental health, risk and functioning
      dimensions at admission. All needs improved significantly over the course of the
      service episode. Youth and caregiver strengths at admission were associated with
      significant improvements in youth behavioral needs areas at discharge. The
      findings support the importance of assessing and incorporating youth and
      caregiver strengths in planning and delivering public mental health services.

PMID- 22160303
TI  - Ghrelin attenuates brain injury after traumatic brain injury and uncontrolled
      hemorrhagic shock in rats.
AB  - Traumatic brain injury (TBI) and hemorrhagic shock often occur concomitantly due
      to multiple injuries. Gastrointestinal dysfunction occurs frequently in patients
      with TBI. However, whether alterations in the gastrointestinal system are
      involved in modulating neuronal damage and recovery after TBI is largely
      neglected. Ghrelin is a "gut-brain" hormone with multiple functions including
      antiinflammation and antiapoptosis. The purpose of this study was to determine
      whether ghrelin attenuates brain injury in a rat model of TBI and uncontrolled
      hemorrhage (UH). To study this, brain injury was induced by dropping a 450-g
      weight from 1.5 m onto a steel helmet attached to the skull of male adult rats.
      Immediately after TBI, a midline laparotomy was performed and both lumbar veins
      were isolated and severed at the junction with the vena cava. At 45 min after
      TBI/UH, ghrelin (4, 8 or 16 nmol/rat) or 1 mL normal saline (vehicle) was
      intravenously administered. Brain levels of TNF-alpha and IL-6, and cleaved PARP
      1 levels in the cortex were measured at 4 h after TBI/UH. Beam balance test,
      forelimb placing test and hindlimb placing test were used to assess sensorimotor
      and reflex function. In additional groups of animals, ghrelin (16 nmol/rat) or
      vehicle was subcutaneously (s.c.) administered daily for 10 d after TBI/UH. The
      animals were monitored for 28 d to record body weight changes, neurological
      severity scale and survival. Our results showed that ghrelin downregulated brain
      levels of TNF-alpha and IL-6, reduced cortical levels of cleaved PARP-1, improved
      sensorimotor and reflex functions, and decreased mortality after TBI/UH. Thus,
      ghrelin has a great potential to be further developed as an effective
      resuscitation approach for the trauma victims with brain injury and severe blood
      loss.

PMID- 22160304
TI  - Nadph oxidase regulates alveolar epithelial sodium channel activity and lung
      fluid balance in vivo via O-2 signaling.
AB  - To define roles for reactive oxygen species (ROS) and epithelial sodium channel
      (ENaC) in maintaining lung fluid balance in vivo, we used two novel whole animal
      imaging approaches. Live X-ray fluoroscopy enabled quantification of air space
      fluid content of C57BL/6J mouse lungs challenged by intratracheal (IT)
      instillation of saline; results were confirmed by using conventional lung wet-to
      dry weight ratios and Evans blue as measures of pulmonary edema. Visualization
      and quantification of ROS produced in lungs was performed in mice that had been
      administered a redox-sensitive dye, hydro-Cy7, by IT instillation. We found that
      inhibition of NADPH oxidase with a Rac-1 inhibitor, NSC23766, resulted in
      alveolar flooding, which correlated with a decrease in lung ROS production in
      vivo. Consistent with a role for Nox2 in alveolar fluid balance, Nox2(-/-) mice
      showed increased retention of air space fluid compared with wild-type controls.
      Interestingly, fluoroscopic analysis of C57BL/6J lungs IT instilled with LPS
      showed an acute stimulation of lung fluid clearance and ROS production in vivo
      that was abrogated by the ROS scavenger tetramethylpiperidine-N-oxyl (TEMPO).
      Acute application of LPS increased the activity of 20 pS nonselective ENaC
      channels in rat type 1 cells; the average number of channel and single-channel
      open probability (NPo) increased from 0.14 +/- 0.04 to 0.62 +/- 0.23. Application
      of TEMPO to the same cell-attached recording caused an immediate significant
      decrease in ENaC NPo to 0.04 +/- 0.03. These data demonstrate that, in vivo, ROS
      has the capacity to stimulate lung fluid clearance by increasing ENaC activity.

PMID- 22160305
TI  - Pulmonary T cell activation in response to chronic particulate air pollution.
AB  - The purpose of this study was to investigate the effects of chronically inhaled
      particulate matter <2.5 MUm (PM(2.5)) on inflammatory cell populations in the
      lung and systemic circulation. A prominent component of air pollution exposure is
      a systemic inflammatory response that may exaggerate chronic diseases such as
      atherosclerosis and insulin resistance. T cell response was measured in wild-type
      C57B/L6, Foxp3-green fluorescent protein (GFP) "knockin," and chemokine receptor
      3 knockout (CXCR3(-/-)) mice following 24-28 wk of PM(2.5) or filtered air.
      Chronic PM(2.5) exposure resulted in increased CXCR3-expressing CD4(+) and CD8(+)
      T cells in the lungs, spleen, and blood with elevation in CD11c(+) macrophages in
      the lung and oxidized derivatives of 1-palmitoyl-2-arachidonyl-sn-glycero-3
      phosphorylcholine in wild-type mice. CXCR3 deficiency decreased T cells in the
      lung. GFP(+) regulatory T cells increased with PM(2.5) exposure in the spleen and
      blood of Foxp3-GFP mice but were present at very low levels in the lung
      irrespective of PM(2.5) exposure. Mixed lymphocyte cultures using primary,
      PM(2.5)-treated macrophages demonstrated enhanced T cell proliferation. Our
      experiments indicate that PM(2.5) potentiates a proinflammatory Th1 response
      involving increased homing of CXCR3(+) T effector cells to the lung and
      modulation of systemic T cell populations.

PMID- 22160306
TI  - Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in
      preterm lamb lungs.
AB  - The proinflammatory stimulus of chorioamnionitis is commonly associated with
      preterm delivery. Women at risk of preterm delivery receive antenatal
      glucocorticoids to functionally mature the fetal lung. However, the effects of
      the combined exposures of chorioamnionitis and antenatal glucocorticoids on the
      fetus are poorly understood. Time-mated ewes with singleton fetuses received an
      intra-amniotic injection of lipopolysaccharide (LPS) either preceding or
      following maternal intramuscular betamethasone 7 or 14 days before delivery, and
      the fetuses were delivered at 120 days gestational age (GA) (term = 150 days GA).
      Gestation matched controls received intra-amniotic and maternal intramuscular
      saline. Compared with saline controls, intra-amniotic LPS increased inflammatory
      cells in the bronchoalveolar lavage and myeloperoxidase, Toll-like receptor 2 and
      4 mRNA, PU.1, CD3, and Foxp3-positive cells in the fetal lung. LPS-induced lung
      maturation measured as increased airway surfactant and improved lung gas volumes.
      Intra-amniotic LPS-induced inflammation persisted until 14 days after exposure.
      Betamethasone treatment alone induced modest lung maturation but, when
      administered before intra-amniotic LPS, suppressed lung inflammation.
      Interestingly, betamethasone treatment after LPS did not counteract inflammation
      but enhanced lung maturation. We conclude that the order of exposures of intra
      amniotic LPS or maternal betamethasone had large effects on fetal lung
      inflammation and maturation.

PMID- 22160307
TI  - Lung heparan sulfates modulate K(fc) during increased vascular pressure: evidence
      for glycocalyx-mediated mechanotransduction.
AB  - Lung endothelial cells respond to changes in vascular pressure through
      mechanotransduction pathways that alter barrier function via non-Starling
      mechanism(s). Components of the endothelial glycocalyx have been shown to
      participate in mechanotransduction in vitro and in systemic vessels, but the
      glycocalyx's role in mechanosensing and pulmonary barrier function has not been
      characterized. Mechanotransduction pathways may represent novel targets for
      therapeutic intervention during states of elevated pulmonary pressure such as
      acute heart failure, fluid overload, and mechanical ventilation. Our objective
      was to assess the effects of increasing vascular pressure on whole lung
      filtration coefficient (K(fc)) and characterize the role of endothelial heparan
      sulfates in mediating mechanotransduction and associated increases in K(fc).
      Isolated perfused rat lung preparation was used to measure K(fc) in response to
      changes in vascular pressure in combination with superimposed changes in airway
      pressure. The roles of heparan sulfates, nitric oxide, and reactive oxygen
      species were investigated. Increases in capillary pressure altered K(fc) in a
      nonlinear relationship, suggesting non-Starling mechanism(s). nitro-l-arginine
      methyl ester and heparanase III attenuated the effects of increased capillary
      pressure on K(fc), demonstrating active mechanotransduction leading to barrier
      dysfunction. The nitric oxide (NO) donor S-nitrosoglutathione exacerbated
      pressure-mediated increase in K(fc). Ventilation strategies altered lung NO
      concentration and the K(fc) response to increases in vascular pressure. This is
      the first study to demonstrate a role for the glycocalyx in whole lung
      mechanotransduction and has important implications in understanding the
      regulation of vascular permeability in the context of vascular pressure, fluid
      status, and ventilation strategies.

PMID- 22160308
TI  - Geranylgeranyl transferase 1 modulates autophagy and apoptosis in human airway
      smooth muscle.
AB  - Geranylgeranyl transferase 1 (GGT1) is involved in the posttranslational
      prenylation of signaling proteins, such as small GTPases. We have shown that
      blocking the formation of isoprenoids with statins regulates survival of human
      lung mesenchymal cells; thus, we tested the hypothesis that GGT1 may specifically
      modulate programmed cell death pathways in these cells. To this end, human airway
      smooth muscle (HASM) cells were treated with the selective GGT1 inhibitor GGTi
      298. Apoptosis was seen using assays for cellular DNA content and caspase
      activation. Induction of autophagy was observed using transmission electron
      microscopy, immunoblotting for LC3 lipidation and Atg5-12 complex content, and
      confocal microscopy to detect formation of lysosome-localized LC3 punctae.
      Notably, GGT1 inhibition induced expression of p53-dependent proteins, p53
      upregulated modulator of apoptosis (Noxa), and damage-regulated autophagy
      modulator (DRAM), this was inhibited by the p53 transcriptional activation
      inhibitor cyclic-pifithrin-alpha. Inhibition of autophagy with bafilomycin-A1 or
      short-hairpin RNA silencing of Atg7 substantially augmented GGTi-298-induced
      apoptosis. Overall, we demonstrate for the first time that pharmacological
      inhibition of GGT1 induces simultaneous p53-dependent apoptosis and autophagy in
      HASM. Moreover, autophagy regulates apoptosis induction. Thus, our findings
      identify GGT1 as a key regulator of HASM cell viability.

PMID- 22160309
TI  - TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial
      pneumonia.
AB  - Toll-like receptors (TLRs) are required for protective host defense against
      bacterial pathogens. However, the role of TLRs in regulating lung injury during
      Gram-negative bacterial pneumonia has not been thoroughly investigated. In this
      study, experiments were performed to evaluate the role of TLR4 in pulmonary
      responses against Klebsiella pneumoniae (Kp). Compared with wild-type (WT)
      (Balb/c) mice, mice with defective TLR4 signaling (TLR4(lps-d) mice) had
      substantially higher lung bacterial colony-forming units after intratracheal
      challenge with Kp, which was associated with considerably greater lung
      permeability and lung cell death. Reduced expression of granulocyte-macrophage
      colony-stimulating factor (GM-CSF) mRNA and protein was noted in lungs and
      bronchoalveolar lavage fluid of TLR4 mutant mice postintratracheal Kp compared
      with WT mice, and primary alveolar epithelial cells (AEC) harvested from TLR4(lps
      d) mice produced significantly less GM-CSF in vitro in response to heat-killed Kp
      compared with WT AEC. TLR4(lps-d) AEC underwent significantly more apoptosis in
      response to heat-killed Kp in vitro, and treatment with GM-CSF protected these
      cells from apoptosis in response to Kp. Finally, intratracheal administration of
      GM-CSF in TLR4(lps-d) mice significantly decreased albumin leak, lung cell
      apoptosis, and bacteremia in Kp-infected mice. Based on these observations, we
      conclude that TLR4 plays a protective role on lung epithelium during Gram
      negative bacterial pneumonia, an effect that is partially mediated by GM-CSF.

PMID- 22160310
TI  - Detection and identification of bacteria in clinical samples by 16S rRNA gene
      sequencing: comparison of two different approaches in clinical practice.
AB  - Amplification and sequence analysis of the 16S rRNA gene can be applied to detect
      and identify bacteria in clinical samples. We examined 75 clinical samples (17
      culture-positive, 58 culture-negative) prospectively by two different PCR
      protocols, amplifying either a single fragment (1343 bp) or two fragments
      (762/598 bp) of the 16S rRNA gene. The 1343 bp PCR and 762/598 bp PCRs detected
      and identified the bacterial 16S rRNA gene in 23 (31 %) and 38 (51 %) of the 75
      samples, respectively. The 1343 bp PCR identified 19 of 23 (83 %) PCR-positive
      samples to species level while the 762/598 bp PCR identified 14 of 38 (37 %)
      bacterial 16S rRNA gene fragments to species level and 24 to the genus level
      only. Amplification of shorter fragments of the bacterial 16S rRNA gene (762 and
      598 bp) resulted in a more sensitive assay; however, analysis of a large fragment
      (1343 bp) improved species discrimination. Although not statistically
      significant, the 762/598 bp PCR detected the bacterial 16S rRNA gene in more
      samples than the 1343 bp PCR, making it more likely to be a more suitable method
      for the primary detection of the bacterial 16S rRNA gene in the clinical setting.
      The 1343 bp PCR may be used in combination with the 762/598 bp PCR when
      identification of the bacterial rRNA gene to species level is required.

PMID- 22160311
TI  - A rare pulmonary infection caused by Arthrographis kalrae.
AB  - Arthrographis kalrae is a rare isolate in clinical specimens. Only ten cases of
      infection with this species have been described so far. To our knowledge, we
      report the first case of a pulmonary infection caused by A. kalrae in a patient
      with a past history of stage IIA Hodgkin's lymphoma and demonstrate that this
      organism can act as an opportunistic human pathogen.

PMID- 22160312
TI  - Helicobacter pylori isolates from Greek children express type 2 and type 1 Lewis
      and alpha1,6-glucan antigens in conjunction with a functional type IV secretion
      system.
AB  - Helicobacter pylori infection is often acquired in childhood and can persist for
      life. Previous studies in adult patients have shown that H. pylori isolates from
      North American and European hosts express predominantly type 2 Lewis x (Le(x))
      and Le(y) epitopes, while Asian strains have the capacity to express type 1 Le(a)
      and Le(b) structures. In order to understand the influence of environmental and
      host factors on the expression of Le antigens, we analysed 50 Greek H. pylori
      isolates from symptomatic children. Both CagA-positive and -negative strains were
      evaluated. The expression of Le antigens was determined by whole-cell indirect
      ELISA (WCE), and LPS profiles were assessed by gel electrophoresis and
      immunoblotting. Occurrence of Le(x) and/or Le(y) antigens was confirmed in 35 of
      the isolates (70 %) while 15 of the isolates were non-typable. It was found that
      11 of the paediatric isolates had the propensity to express type 1 Le(b) blood
      group antigen (22 %), a feature relatively uncommon in H. pylori isolates from
      adults. One strain expressed both Le(b) and Le(a) antigens. The majority of the
      isolates (49/50, 98 %) expressed alpha1,6-glucan, an antigenic non-Le determinant
      present in the outer core region of H. pylori LPS. All Le(x)- and Le(y)
      expressing strains also carried a functional cag pathogenicity island-encoding a
      type IV secretion system, capable of translocating CagA protein, as well as the
      vacAs1 allele, suggesting that Le(x) and Le(y) epitopes may aid the persistence
      of more aggressive strains. No association between bacterial virulence
      characteristics and the histopathological observations was evident.

PMID- 22160313
TI  - Comparison of the effects of subinhibitory concentrations of ciprofloxacin and
      colistin on the morphology of cardiolipin domains in Escherichia coli membranes.
AB  - Membrane domains characterized by unique protein and lipid composition allow for
      compartmentalization and regulation of various biological processes. In
      Escherichia coli cardiolipin domains play a key role in the dynamic organization
      of bacterial membranes, and their distribution depends on the stage of the cell
      cycle. We studied the influence of subinhibitory concentrations of ciprofloxacin
      and colistin on the morphology and distribution of E. coli cardiolipin domains.
      Using the fluorescent dye 10-N-nonyl acridine orange we found that exposure of
      bacteria to ciprofloxacin significantly increased the percentage of filamentous
      cells with altered morphology of the cardiolipin domains, while colistin did not
      induce any significant changes. These results allow us to conclude that
      inhibition of DNA gyrase causes effects even at the bacterial membrane level and
      those changes can be easily visualized using 10-N-nonyl acridine orange.

PMID- 22160314
TI  - In vitro antibacterial activity of different adenosine analogues.
AB  - Nucleoside analogues may represent good candidates for the discovery of new
      antibacterial agents, therefore, a library of adenosine analogues was assessed
      for their antibacterial activity, and the relationship between the structure and
      activity of these molecules was outlined. Antibacterial activity was evaluated
      against that of reference strains of Staphylococcus aureus, Staphylococcus
      epidermidis, Streptococcus pneumoniae, Escherichia coli and Pseudomonas
      aeruginosa. We tested 54 adenosine analogues, modified both at ribose and base
      moieties, including adenine and 1/3-deazaadenine derivatives substituted in the 2
      and/or N(6)-positions and bearing N-9 sugar moieties, such as ribose, 2'
      deoxyribose, 3'-deoxyribose, 2',3'-dideoxyribose or cycloalkyl groups like
      cyclopentane. The data obtained, MIC and minimal bactericidal concentrations
      demonstrated that the presence of bulky substituents such as cycloheptyl and
      cyclooctyl rings on the N(6)-amino, together with a chlorine atom in the 2
      position, conferred antibacterial activity against the Gram-positive group with
      MIC values ranging from 16 to 128 mg l(-1). The intact sugar moiety seemed to be
      not essential for antimicrobial activity and nucleosides bearing deoxyribose or
      cyclopentyl groups associated with bulky substituents in N(6)-position showed
      good antimicrobial properties. Furthermore, N-1 proved to be non-crucial and the
      2-chloro-N(6)-cyclooctyl-1-deaza-3'-deoxyadenosine and 2',3'-dideoxyadenosine
      compounds were among the more active in the series with an MIC of 32 mg l(-1)
      against Staph. aureus and Strep. pneumoniae. None of the analogues was active
      against the two gram-negative species tested. Hence, adenosine derivatives
      bearing bulky substituents in the N(6)-position may represent good lead compounds
      for the future discovery of a novel series of antibacterial agents.

PMID- 22160315
TI  - Development of monoclonal antibodies to recombinant terrelysin and
      characterization of expression in Aspergillus terreus.
AB  - Aspergillus terreus is an emerging pathogen that mostly affects immunocompromised
      patients, causing infections that are often difficult to manage therapeutically.
      Current diagnostic strategies are limited to the detection of fungal growth using
      radiological methods or biopsy, which often does not enable species-specific
      identification. There is thus a critical need for diagnostic techniques to enable
      early and specific identification of the causative agent. In this study, we
      describe monoclonal antibodies (mAbs) developed to a previously described
      recombinant form of the haemolysin terrelysin. Sixteen hybridomas of various IgG
      isotypes were generated to the recombinant protein, of which seven demonstrated
      reactivity to the native protein in hyphal extracts. Cross-reactivity analysis
      using hyphal extracts from 29 fungal species, including 12 Aspergillus species
      and five strains of A. terreus, showed that three mAbs (13G10, 15B5 and 10G4)
      were A. terreus-specific. Epitope analysis demonstrated mAbs 13G10 and 10G4
      recognize the same epitope, PSNEFE, while mAb 15B5 recognizes the epitope
      LYEGQFHS. Time-course studies showed that terrelysin expression was highest
      during early hyphal growth and dramatically decreased after mycelial expansion.
      Immunolocalization studies demonstrated that terrelysin was not only localized
      within the cytoplasm of hyphae but appeared to be more abundant at the hyphal
      tip. These findings were confirmed in cultures grown at room temperature as well
      as at 37  degrees C. Additionally, terrelysin was detected in the supernatant of
      A. terreus cultures. These observations suggest that terrelysin may be a
      candidate biomarker for A. terreus infection.

PMID- 22160316
TI  - Method comparison for molecular typing of French and Tunisian Mycoplasma
      genitalium-positive specimens.
AB  - In this study, 76 French and Tunisian urogenital specimens were subjected to
      molecular typing by using the two main Mycoplasma genitalium molecular typing
      methods, the mgpB single nucleotide polymorphism (SNP) typing method and the
      combination analysis of a variable-number tandem-repeat (VNTR) marker in MG309
      and mgpB SNP. Furthermore, we tried to develop a multiple-locus VNTR analysis
      (MLVA) method. The genome of M. genitalium G37(T) was analysed for VNTRs and four
      VNTRs were used for an MLVA. The method, applied directly on clinical specimens,
      was based on a genescan analysis of VNTR loci labelled with fluorescent dyes by
      using multiplex PCR and capillary electrophoresis. This method had a 1.00
      diversity index (DI) while the mgpB SNP typing and the combination of MG309 and
      mgpB SNPs had DIs of 0.853 and 0.989, respectively. However, among the sets of
      two concurrent specimens, taken at the same time from the urogenital tracts of 12
      patients, only nine had matching MLVA profiles, while the two other methods gave
      identical profiles for all specimens amplified, except for one set. Moreover,
      eight new sequence types were described with the mgpB SNP typing method. The
      three molecular typing methods revealed a genetic heterogeneity, suggesting that
      M. genitalium was endemic in France and Tunisia and that the infections were not
      due to the clonal dissemination of one strain. Comparison of the typing results
      obtained with the three methods showed that the MLVA assay seemed too
      discriminatory to be used in future studies of sexual networks of M. genitalium
      infection. According to the discriminatory power and the feasibility of each mgpB
      based method, we recommend that the mgpB analysis be used for general
      epidemiological studies and that the combination of MG309-STR and mgpB SNP
      methods should be used for sexual-network studies of M. genitalium infection.

PMID- 22160317
TI  - Streptomyces temperate bacteriophage integration systems for stable genetic
      engineering of actinomycetes (and other organisms).
AB  - phiC31, phiBT1, R4, and TG1 are temperate bacteriophages with broad host
      specificity for species of the genus Streptomyces. They form lysogens by
      integrating site-specifically into diverse attB sites located within individual
      structural genes that map to the conserved core region of streptomycete linear
      chromosomes. The target genes containing the phiC31, phiBT1, R4, and TG1 attB
      sites encode a pirin-like protein, an integral membrane protein, an acyl-CoA
      synthetase, and an aminotransferase, respectively. These genes are highly
      conserved within the genus Streptomyces, and somewhat conserved within other
      actinomycetes. In each case, integration is mediated by a large serine
      recombinase that catalyzes unidirectional recombination between the bacteriophage
      attP and chromosomal attB sites. The unidirectional nature of the integration
      mechanism has been exploited in genetic engineering to produce stable
      recombinants of streptomycetes, other actinomycetes, eucaryotes, and archaea. The
      phiC31 attachment/integration (Att/Int) system has been the most widely used, and
      it has been coupled with the phiBT1 Att/Int system to facilitate combinatorial
      biosynthesis of novel lipopeptide antibiotics in Streptomyces fradiae.

PMID- 22160318
TI  - Comparative use of InDel and SSR markers in deciphering the interspecific
      structure of cultivated citrus genetic diversity: a perspective for genetic
      association studies.
AB  - Genetic stratification associated with domestication history is a key parameter
      for estimating the pertinence of genetic association study within a gene pool.
      Previous molecular and phenotypic studies have shown that most of the diversity
      of cultivated citrus results from recombination between three main species: C.
      medica (citron), C. reticulata (mandarin) and C. maxima (pummelo). However, the
      precise contribution of each of these basic species to the genomes of secondary
      cultivated species, such as C. sinensis (sweet orange), C. limon (lemon), C.
      aurantium (sour orange), C. paradisi (grapefruit) and recent hybrids is unknown.
      Our study focused on: (1) the development of insertion-deletion (InDel) markers
      and their comparison with SSR markers for use in genetic diversity and
      phylogenetic studies; (2) the analysis of the contributions of basic taxa to the
      genomes of secondary species and modern cultivars and (3) the description of the
      organisation of the  Citrus gene pool, to evaluate how genetic association
      studies should be done at the cultivated Citrus gene pool level. InDel markers
      appear to be better phylogenetic markers for tracing the contributions of the
      three ancestral species, whereas SSR markers are more useful for intraspecific
      diversity analysis. Most of the genetic organisation of the Citrus gene pool is
      related to the differentiation between C. reticulata, C. maxima and C. medica.
      High and generalised LD was observed, probably due to the initial differentiation
      between the basic species and a limited number of interspecific recombinations.
      This structure precludes association genetic studies at the genus level without
      developing additional recombinant populations from interspecific hybrids.
      Association genetic studies should also be affordable at intraspecific level in a
      less structured pool such as C. reticulata.

PMID- 22160319
TI  - In memoriam: John D. Baxter, M.D., 1940-2011.

PMID- 22160320
TI  - Hyperphosphorylated tau in young and middle-aged subjects.
AB  - The brain tissue obtained from ninety-five cognitively unimpaired subjects, with
      ages ranging from 22 to 50 years upon death, were immunohistochemically assessed
      for neurodegenerative changes, i.e., hyperphosphorylated tau (HPtau) and beta
      amyloid (Abeta) pathology in predilection neuroanatomical areas. HPtau pathology
      was observed in the transentorhinal cortex and/or the locus coeruleus (LC) in 33%
      of the subjects, without any obvious risk factors known to alter the microtubule
      associated protein. HPtau pathology was noted in the LC in 25 out of 83 subjects
      (30%), lacking concomitant cortical Abeta or transentorhinal HPtau pathology.
      This observation was present even when assessing only one routine section of 7
      MUm thickness. The recent suggestion of prion-like propagation of
      neurodegeneration and the finding of neurodegeneration being quite common in
      middle-aged persons is alarming. It is noteworthy, however, that a substantial
      number of neurologically unimpaired subjects even at a very old age display only
      sparse to modest extent of neurodegenerative pathology. Thus, only a subset of
      subjects with neurodegenerative changes early in life seem to progress to a
      symptomatic disease with ageing. This observation brings forth the notion that
      other, yet unknown modifying factors influence the progression of degeneration
      that leads to a symptomatic disorder. The known association between alterations
      in the LC and mood disorders, and the finding of the LC being frequently affected
      with HPtau pathology suggest that clinicopathological studies on young subjects
      both with or without mood disorders are warranted.

PMID- 22160321
TI  - Myofibrillar disorganization characterizes myopathy of camptocormia in
      Parkinson's disease.
AB  - Camptocormia is a highly disabling syndrome that occurs in various diseases but
      is particularly associated with Parkinson's disease (PD). Although first
      described nearly 200 years ago, the morphological changes associated with
      camptocormia are still under debate and the pathophysiology is unknown. We
      analyzed paraspinal muscle biopsies of 14 PD patients with camptocormia and
      compared the findings to sex-matched postmortem controls of comparable age to
      exclude biopsy site-specific changes. Camptocormia in PD showed a consistent
      lesion pattern composed of myopathic changes with type-1 fiber hypertrophy, loss
      of type-2 fibers, loss of oxidative enzyme activity, and acid phosphatase
      reactivity of lesions. Ultrastructurally, myofibrillar disorganization and Z-band
      streaming up to electron-dense patches/plaques were seen in the lesions. No
      aberrant protein aggregation, signs of myositis or mitochondriopathy were found,
      but the mitochondrial content of paraspinal muscles in patients and controls was
      markedly higher than known from limb biopsies. Additionally, we were able to
      demonstrate a link between the severity of the clinical syndrome and the degree
      of the myopathic changes. Because of the consistent lesion pattern, we propose
      criteria for the diagnosis of camptocormia in PD from muscle biopsies. The
      morphological changes show obvious parallels to the muscle pathology of
      experimental tenotomy reported in the 1970s, which depend on an intact
      innervation and do not occur after interruption of the myotactic reflexes. A
      dysregulation of the proprioception could be part of the pathogenesis of
      camptocormia in Parkinson's disease, particularly in view of the clinical
      symptoms of rigidity and loss of muscle strength.

PMID- 22160323
TI  - Failures and complications in pelvic floor surgery.
AB  - OBJECTIVES: To review current literature on the failures of different surgical
      approaches in pelvic floor surgery, in particular the use of alloplastic
      materials, and to analyze complications related to them. METHODS: A Medline
      search was performed to retrieve English language literature (from the year 1995
      to 2011) on the success rates, failures, and complications profiles of pelvic
      floor surgery. Search terms used are "pelvic organ prolapse," "stress urinary
      incontinence," "complications," "vaginal mesh," "mid-urethral slings," and
      "colposuspension." The review includes surgical techniques for the correction of
      pelvic organ prolapse and stress urinary incontinence. Failure rates and
      complications in different studies are compiled and analyzed. RESULTS: Use of
      synthetic materials in pelvic organ prolapse surgery has reduced surgical
      failures but it is associated with an increased risk of complications compared to
      traditional surgical repairs. Synthetic mid-urethral slings for stress urinary
      incontinence seem to have good success rates over long term, but they have unique
      complication profile including de novo development of overactive bladder, voiding
      dysfunction, sling exposures, dyspareunia, and long-term pain. However, some of
      these complications seem to be related to wrong surgical indications and improper
      surgical techniques, although some complications may be directly related to the
      use of synthetic material itself. CONCLUSION: Use of synthetic materials in
      pelvic floor surgery has definitely reduced surgical failures, but at the same
      time, it is associated with an increased risk of complications (some of which are
      unique to synthetic materials) compared to traditional surgical repairs.

PMID- 22160324
TI  - Partial stapled hemorrhoidopexy: a minimally invasive technique for hemorrhoids.
AB  - PURPOSE: This study was designed to assess the safety, efficacy, and
      postoperative outcomes of partial stapled hemorrhoidopexy (PSH). METHODS: A
      prospective study was conducted between February and March 2010. PSH was
      performed with single-window anoscopes for single isolated hemorrhoids, bi-window
      anoscopes for two isolated hemorrhoids, and tri-window anoscopes for three
      isolated hemorrhoids or circumferential hemorrhoids. The data pertaining to
      demographics, preoperative characteristics and postoperative outcomes were
      collected and analyzed. RESULTS: Forty-four eligible patients underwent PSH.
      Single-window anoscopes were used in 2 patients, and bi- and tri-window anoscopes
      in 6 and 36 patients. The blood loss in patients with single-window, bi-window,
      and tri-window anoscopes was 6.0 ml (range 5.0-7.0 ml), 5.0 ml (range 5.0-6.5
      ml), and 5.0 ml (4.5-14.5 ml) (P = 0.332). The mean postoperative visual analog
      scale score for pain was 3 (range, 1-4), 2 (range 1-4), 3 (range 2-6), 1 (range 0
      3), 1 (range 0-2) and 2 (range 2-4) at 12 h, days 1, 2, 3, and 7, and at first
      defecation. The rate of urgency was 9.1%. No patients developed anal incontinence
      or stenosis. The 1-year recurrence rate of prolapsing hemorrhoids was 2.3%.
      CONCLUSIONS: Partial stapled hemorrhoidopexy appears to be a safe and effective
      technique for grade III-IV hemorrhoids. Encouragingly, PSH is associated with
      mild postoperative pain, few urgency episodes, and no stenosis or anal
      incontinence.

PMID- 22160325
TI  - Green tea protects human osteoblasts from cigarette smoke-induced injury:
      possible clinical implication.
AB  - PURPOSE: Recent reports discuss the altered bone homeostasis in cigarette
      smokers, being a risk factor for osteoporosis and negatively influencing fracture
      healing. Cigarette smoke is known to induce oxidative stress in the body via an
      increased production of reactive oxygen species (ROS). These increases in ROS are
      thought to damage the bone-forming osteoblasts. Naturally occurring polyphenols
      contained in green tea extract (GTE), e.g., catechins, are known to have anti
      oxidative properties. Therefore, the aim of this study was to investigate whether
      GTE and especially catechins protect primary human osteoblasts from cigarette
      smoke-induced damage and to identify the underlying mechanisms. METHODS: Primary
      human osteoblasts were isolated from patients' femur heads. Cigarette smoke
      medium (CSM) was obtained using a gas-washing bottle and standardized by its
      optical density (OD(320)) at lambda = 320 nm. ROS formation was measured using
      2'7'dichlorofluorescein diacetate, and osteoblasts' viability was detected by
      resazurin conversion. RESULTS: Co-, pre-, and post-incubation with GTE and
      catechins significantly reduced ROS formation and thus improved the viability of
      CSM-treated osteoblasts. Besides GTE's direct radical scavenging properties, pre
      incubation with both GTE and catechins protected osteoblasts from CSM-induced
      damage. Inhibition of the anti-oxidative enzyme HO-1 significantly reduced the
      protective effect of GTE and catechins emphasizing the key role of this enzyme in
      GTE anti-oxidative effect. CONCLUSIONS: Our data suggest possible beneficial
      effects on bone homeostasis, fracture healing, and bone mineral density following
      a GTE-rich diet or supplementation.

PMID- 22160322
TI  - Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms.
AB  - Neurofibromas, schwannomas and malignant peripheral nerve sheath tumors (MPNSTs)
      all arise from the Schwann cell lineage. Despite their common origin, these tumor
      types have distinct pathologies and clinical behaviors; a growing body of
      evidence indicates that they also arise via distinct pathogenic mechanisms.
      Identification of the genes that are mutated in genetic diseases characterized by
      the development of either neurofibromas and MPNSTs [neurofibromatosis type 1
      (NF1)] or schwannomas [neurofibromatosis type 2 (NF2), schwannomatosis and Carney
      complex type 1] has greatly advanced our understanding of these mechanisms. The
      development of genetically engineered mice with ablation of NF1, NF2,
      SMARCB1/INI1 or PRKAR1A has confirmed the key role these genes play in peripheral
      nerve sheath tumorigenesis. Establishing the functions of the NF1, NF2,
      SMARCB1/INI1 and PRKAR1A gene products has led to the identification of key
      cytoplasmic signaling pathways promoting Schwann cell neoplasia and identified
      new therapeutic targets. Analyses of human neoplasms and genetically engineered
      mouse models have established that interactions with other tumor suppressors such
      as TP53 and CDKN2A promote neurofibroma-MPNST progression and indicate that
      intratumoral interactions between neoplastic and non-neoplastic cell types play
      an essential role in peripheral nerve sheath tumorigenesis. Recent advances have
      also provided new insights into the identity of the neural crest-derived
      populations that give rise to different types of peripheral nerve sheath tumors.
      Based on these findings, we now have an initial outline of the molecular
      mechanisms driving the pathogenesis of neurofibromas, MPNSTs and schwannomas.
      However, this improved understanding in turn raises a host of intriguing new
      questions.

PMID- 22160326
TI  - Evaluation of selected cognitive functions before and after surgery for primary
      hyperparathyroidism.
AB  - BACKGROUND AND AIMS: Cognitive functions have been reported to be impaired in
      patient with primary hyperparathyroidism (pHPT). The aim of this psychological
      study was to evaluate cognitive disturbances in pHPT in relation to serum calcium
      levels before and after surgery. PATIENTS AND METHODS: A prospective, case
      control study with 1-year follow-up of 35 pHPT patients versus 35 matched
      controls was undertaken. All patients were tested before surgery and at 12-18
      months following surgery with a battery of selected cognitive function
      psychological tools: Benton Visual Retention Test (BVRT), Wisconsin Card Sorting
      Test (WCST), Memory Verbal Learning Test (DCS), The Rey's Auditory Verbal
      Learning Test (RAVLT), Trail Making Test A & B, Verbal Fluency Test, and Beck
      Depression Inventory. In addition to psychological testing, serum calcium,
      parathyroid hormone and phosphate levels were evaluated. RESULTS: The following
      cognitive functions of pHPT patients versus controls were deteriorated before
      surgery: impaired concentration, decreased nonverbal learning process,
      difficulties in using direct memory, verbal fluency and visual constructive
      abilities. However, no correlation was found between serum calcium levels and the
      results of neuropsychological tests. In longitudinal comparison of pHPT patients
      before and 1 year after surgery, there was a significant improvement in visual
      memory, visual-constructive abilities and direct memory. CONCLUSIONS: pHPT
      patients have significantly decreased concentration level, nonverbal learning
      process, access to verbal resources and constructional and visual memory ability.
      Thus, neuropsychological testing may be useful in the decision making for early
      surgery in patients with mild asymptomatic disease in order to avoid further
      deterioration of cognitive functions.

PMID- 22160327
TI  - The adaptor-related protein complex 2, alpha 2 subunit (AP2alpha2) gene is a
      peroxisome proliferator-activated receptor cardiac target gene.
AB  - A peroxisome proliferator-actived receptor (PPAR) response element (RE) in the
      promoter region of the adaptor-related protein complex 2, alpha 2 subunit
      (AP2alpha2) of mouse heart has been identified. The steroid hormone nuclear PPARs
      and the retinoid X receptors (RXRs) are important transcriptional factors that
      regulate gene expression, cell differentiation and lipid metabolism. They form
      homo- (RXR) and hetero- (PPAR-RXR) dimers that bind DNA at various REs. The
      AP2alpha2 gene is part of complex and process that transports lipids and proteins
      from the plasma membrane to the endosomal system. A PPAR activator (Wy14643) and
      DMSO (vehicle) was introduced into control and delta337T thyroid hormone receptor
      (TRbeta1) transgenic mice. Heart tissue was extracted and AP2alpha2 gene
      expression was compared using Affymetrix expression arrays and qRT PCR among four
      groups [control, control with Wy14643, delta337T TRbeta1 and delta337T TRbeta1
      with Wy14643]. The gene expression of AP2alpha2 in the Wy14643 control and
      transgenic mouse groups was significantly up regulated over the vehicle mouse
      groups in both the array (p < 0.01) and qRT PCR (p < 0.01) studies. Duplex oligo
      DNAs containing the PPAR/RXR motif (AGGTCA/TCCAGT) from the AP2alpha2 promoter
      were used in EMSA to verify binding of the PPAR and RXR receptors to their REs.
      pGL4.0 [Luc] constructs of the AP2alpha2 promoter with and without the PPAR/RXR
      motifs were co-transfected with mouse PPARalpha, beta or gamma1 into HepG2 cells
      and used in lucerifase assays to verify gene activation. In conclusion our study
      revealed that PPARalpha regulates the mouse cardiac AP2alpha2 gene in both the
      control and transgenic mouse.

PMID- 22160328
TI  - High-level expression and characterization of a highly thermostable chitosanase
      from Aspergillus fumigatus in Pichia pastoris.
AB  - The sequence of an endo-chitosanase gene (CSN) from Aspergillus fumigatus was
      optimized based on the preferred codons of Pichia pastoris and synthesized in
      vitro through overlapping PCR (CSN-P). The gene was cloned into a yeast
      expression vector, pHBM905A, and secretorily expressed in Pichia pastoris GS115.
      The yield of CSN-P reached ~3 mg/ml with a high-density fermentation in a 14 l
      fermenter and the enzyme activity was ~25,000 U/ml. The enzyme had half-lives of
      2.5 h at 80 degrees C, 1 h at 90 degrees C and 32 min at 100 degrees C. It
      retained 70% activity after incubation with 10 M urea at room temperature for 30
      min. This enzyme was used for a large-scale preparation of oligosaccharides: 3 g
      enzyme converted 200 kg chitosan into oligosaccharides in 24 h at 60 degrees C.

PMID- 22160329
TI  - Development and structure of a novel barrier membrane composed of drug-loaded
      poly(lactic-co-glycolic acid) particles for guided bone regeneration.
AB  - A novel barrier membrane composed of poly(lactic-co-glycolic acid) particles
      loaded with dexamethasone (DEX) as a bioactive molecule was produced via a
      modified nanoprecipitation method without any mixing. The particle membranes had
      a bilayer structure: one side was smooth and had a compact surface that was
      connected to larger particles, while the opposite side was rough, porous and
      connected to smaller particles. Additionally, a cross-section of the particle
      membrane had a porous structure with nano and micro sized irregular pores.
      Process optimization revealed that NaCl concentration in the water phase, with
      acetone as solvent and water as a non-solvent, played critical roles in
      determining the properties of the particle membranes, such as DEX encapsulation
      efficiency, thickness and surface morphologies of the particle membranes. A novel
      barrier membrane containing DEX using polymer particle drug capture technology
      has been successfully developed.

PMID- 22160330
TI  - Fed-batch versus batch cultures of Yarrowia lipolytica for gamma-decalactone
      production from methyl ricinoleate.
AB  - Constant medium feeding rate and intermittent fed-batch fermentation strategies
      were investigated aiming to increase the yields of gamma-decalactone production
      by Yarrowia lipolytica, using methyl ricinoleate as substrate and ricinoleic acid
      source. The accumulation of another compound, 3-hydroxy-gamma-decalactone, was
      also analyzed since it derives from the direct precursor of gamma-decalactone
      thereby providing information about the enzymatic activities of the pathway. Both
      strategies were compared with the traditional batch mode in terms of overall
      productivity and yield in respect to the substrate. Although the productivity of
      gamma-decalactone was considerably higher in the batch mode (168 mg l(-1) h(-1)),
      substrate conversion to lactone (73 mg gamma-decalactone g(-1)) was greater in
      the intermittent fed-batch giving 6.8 g gamma-decalactone l(-1). This last
      strategy therefore has potential for gamma-decalactone production at an
      industrial level.

PMID- 22160331
TI  - Extracellular protease in Actinomycetes culture supernatants inhibits and
      detaches Staphylococcus aureus biofilm formation.
AB  - Bacterial biofilms are associated with chronic infections due to their resistance
      to antimicrobial agents. Staphylococcus aureus is a versatile human pathogen and
      can form biofilms on human tissues and diverse medical devices. To identify novel
      biofilm inhibitors of S. aureus, the supernatants from a library of 458
      Actinomycetes strains were screened. The culture supernatants (1% v/v) of more
      than 10 Actinomycetes strains inhibited S. aureus biofilm formation by more than
      80% without affecting the growth. The culture supernatants of these biofilm
      reducing Actinomycetes strains contained a protease (equivalent to 0.1 MUg
      proteinase K ml(-1)), which both inhibited S. aureus biofilm formation and
      detached pre-existing S. aureus biofilms. This study suggests that protease
      treatment could be a feasible tool to reduce and eradicate S. aureus biofilms.

PMID- 22160332
TI  - Floral odor bouquet loses its ant repellent properties after inhibition of
      terpene biosynthesis.
AB  - In their natural environment, plants are synchronously confronted with mutualists
      and antagonists, and thus benefit from signals that contain messages for both
      functional groups of interaction partners. Floral scents are complex blends of
      volatiles of different chemical classes, including benzenoids and terpenoids. It
      has been hypothesized that benzenoids have evolved as pollinator attracting
      signals, while monoterpenoids serve as defensive compounds against antagonists.
      In order to test this hypothesis, we reduced terpene emission in flowers of Phlox
      paniculata with specific biosynthetic inhibitors and compared the responses of
      Lasius niger ants to natural and inhibited floral scent bouquets. While the
      natural odors were strongly repellent to ants, the bouquets with a reduced
      emission rate of terpenoids were not. The loss of the flowers' ability to repel
      ants could be attributed predominantly to reduced amounts of linalool, a
      monoterpene alcohol. Flying flower visitors, mainly hoverflies, did not
      discriminate between the two types of flowers in an outdoor experiment. Since
      individual compounds appear to be capable of either attracting pollinators or
      defending the flower from enemies, the complexity of floral scent bouquets may
      have evolved to allow flowers to respond to both mutualists and antagonists
      simultaneously.

PMID- 22160333
TI  - The positivity assumption and marginal structural models: the example of warfarin
      use and risk of bleeding.
AB  - Estimates of the average causal effect (ACE) of warfarin on the risk of bleeding
      may be confounded by indication as patients at high risk of bleeding are unlikely
      to be prescribed warfarin. One approach to estimating the ACE is inverse
      probability of treatment weighting (IPTW). This study was designed to examine the
      use of IPTW in this setting, and to demonstrate problems with the violation of
      the positivity assumption. We analyzed a case-control study on 4,028 cases of
      gastro-intestinal bleeding and 79,239 controls set in the United Kingdom's
      General Practice Research Database. Warfarin exposure was defined as a
      prescription issued in the 90 days before the index date. Secondary analyses were
      conducted restricted to patients more likely to receive warfarin and with a
      truncated weight distribution, to exclude subjects highly unlikely to be treated.
      The estimated association between warfarin use and bleeding was stronger with
      IPTW [odds ratio (OR): 17.2; 95% confidence interval (CI): 6.5-37.7] than with a
      standard logistic regression model (OR: 2.1; 95% CI: 1.7-2.5). The presence of
      large weights (five subjects with stabilized weight >500) indicated a potential
      violation of the positivity assumption. In the restricted analysis, both IPTW
      (OR: 2.0; 95% CI: 0.4-9.6) and standard regression (OR: 1.6; 95% CI: 1.3-2.0)
      were compatible with a meta-analysis of randomized trials inverse probability of
      treatment weighting is sensitive to the positivity assumption; however, such
      sensitivity may assist in diagnosing off-support inference.

PMID- 22160334
TI  - A drug rape case involving triazolam detected in hair and urine.
AB  - In recent years, there has been heightened awareness regarding the use of drugs
      to modify a person's behavior to facilitate crime. A drug rape case involving the
      potent, short-acting sedative triazolam will be presented. On three occasions,
      the victim consumed green tea and chocolate before being massaged and ultimately
      sexually abused. Screening for alcohol, commonly used drugs and illicit
      substances in blood and urine sampled during the forensic examination 20 h after
      the last incident, was negative. Consequently, hair samples for chemical analysis
      were taken from the assaulted individual 34 days after the last incidents. The
      hair was cut into three 2-cm segments (0-6 cm) that were washed, dissolved in
      extraction solvent and screened and verified by ultra performance liquid
      chromatography coupled with time of flight mass spectrometry (UPLC-TOF-MS) and
      with tandem mass spectrometry (UPLC-MS/MS), respectively. In the 2-cm hair
      segment corresponding to the period of the alleged assaults, the presence of the
      sedative triazolam was revealed at a concentration of 1.0 pg/mg hair. The
      preserved urine sample, taken 20 h after the last incident, was reanalyzed by
      UPLC-MS/MS for metabolites of triazolam, and 39 MUg/l alpha-hydroxytriazolam was
      detected in the hydrolyzed urine. This case illustrates that hair is a valuable
      forensic specimen in situations where natural processes have eliminated the drug
      from typical biological specimens due to delays in the crime being reported.
      Furthermore, it was possible to verify the hair finding with a urine sample by
      detection of a metabolite of triazolam.

PMID- 22160335
TI  - Gelation with Small Molecules: from Formation Mechanism to
      NanostructureArchitecture.
AB  - The mechanism of fiber and fiber network formation of small molecular gelling
      agents is treated on the basis of a generic heterogeneous nucleation model. The
      formation of a crystallite fiber network can take place via the so-called
      crystallographic mismatch branching. At very low supersaturations, unbranched
      fibers form predominantly. As supersaturation increases, small-angle
      crystallographic mismatch branching occurs at the side face of growth fibers. At
      very high supersaturations, the so-called wide-angle crystallographic mismatch
      branching becomes kinetically favorable. Both give rise to the formation of fiber
      networks, but of different types. Controlling the branching of the nanofibers of
      small molecular gelatins allows us to achieve the micro/nanostructure
      architecture of networks having the desired rheological properties. In this
      regard, the engineering of supramolecular functional materials can be achieved by
      constructing and manipulating the micro/nanostructure in terms of a "branching
      creator", or by tuning processing conditions.

PMID- 22160336
TI  - Cholesterol-based gelators.
AB  - This chapter is intended to provide a comprehensive overview of the chemistry and
      molecular structures of cholesterol-based low molecular mass organogelators and
      to describe the underlying principles that are responsible for self-assembly and,
      in turn, organogel formation within this important class of systems. In
      particular, the properties of the resulting organogels are discussed in terms of
      the relationship between the designed structure of the gelator, the nature of the
      gelled organic fluid component, the influence of molecular interactions (pi-pi
      stacking, Van der Waals, hydrogen bonding, ...), and chirality. Emphasis is given
      to the remarkably high synthetic tunability of the cholesterol-based
      organogelators, which enable access to a range of functional gels. The prospects
      for future applications of cholesteryl molecular gels will be illustrated and
      discussed at the end of the chapter.

PMID- 22160337
TI  - Systematic design of amide- and urea-type gelators with tailored properties.
AB  - The formation of gels by structurally highly diverse low molecular weight organic
      molecules is paradigmatically a supramolecular phenomenon. It is based on the
      self-assembly of certain organic molecules and involves highly specific
      noncovalent intermolecular interactions, in particular those inducing
      predominantly unidirectional aggregation. In this chapter, the design of low
      molecular weight gelators that incorporate single or multiple amide units as
      intermolecular hydrogen-bonding functionalities and methods of their preparation
      are given. Many efficient gelators of organic solvents and water could be
      prepared by the structural combination of amidic, carbamate, urea, or oxalamide
      groups and long aliphatic chains or aromatic groups with a large surface. The
      numerous potential applications in slow drug-delivery systems, the fabrication of
      templated materials, and in sensing devices are also discussed.

PMID- 22160338
TI  - Nucleobase-containing gelators.
AB  - Nucleobases are nitrogenous heterocyclic compounds and have high ability to form
      directionally controlled multiple intermolecular interaction, i.e., in-plane
      multiple hydrogen-bonding interactions and stacking interactions perpendicular to
      the plane. Here the recent development of nucleobase-containing low molecular
      mass gelators in aqueous and organic systems is reviewed, and the self-assemblies
      of nucleobase-containing small molecules and their arrangement within the gel are
      discussed from the molecular, and mesoscopic to the macroscopic level in regard
      to becoming a macroscale three-dimensional network. Brief overview of the
      nucleoside-containing supramolecular materials are also presented.

PMID- 22160339
TI  - Chirality Effects in Self-assembled Fibrillar Networks.
AB  - Chirality seems to be intimately associated with the growth and stability of self
      assembled fibrillar networks and with the most common macroscopic property of
      these networks, which is the thermoreversible gelation of the solvent. The
      presence and the relative configurations of stereogenic centers in the structure
      of a small molecule gelator are generally (but not always) observed to be
      critical to its ability to form gels. Symmetry considerations of chiral molecular
      packing provide thermodynamic and kinetic arguments that may explain why
      chirality favors fiber growth. Additionally, molecular chirality is sometimes
      expressed at a scale of nanometers or micrometers and gives rise to twisted or
      coiled fiber structures that are readily observable by microscopic techniques.
      These chiral fiber morphologies have already found some applications as templates
      for helical protein crystallization or for the growth of chiral inorganic
      replicas. The chiroptical properties of assembled chiral molecules, e.g.,
      circular dichroism, allow monitoring of aggregation and may sometimes give
      insights into molecular packing. But determining chiral molecular arrangements in
      the fibers remains a challenge and requires the use of multiple techniques.

PMID- 22160340
TI  - Gelation of liquid crystals with self-assembled fibers.
AB  - Physical gelation of liquid crystals with low molecular weight gelators leads to
      the formation of a new class of anisotropic gels that have great potentials for
      optical, electrical, and photofunctional materials. The liquid crystalline (LC)
      physical gels are microphase-separated anisotropic composites consisting of
      liquid crystals and self-assembled solid fibers. For these materials, the
      isotropic-anisotropic transitions due to liquid crystals and the sol-gel
      transitions due to gelators occur reversibly and independently. The thermal,
      optical, and electrical properties of the LC gels are tuned by the selection and
      combination of the components, which determine the microphase-separated
      structures. LC gels based on room temperature nematic liquid crystals show
      electro-optical switching on twisted nematic and light scattering modes. The
      electro-optical properties can be improved in the presence of fiber additives.
      Discotic liquid crystals that function as hole transport materials have been used
      as LC components of anisotropic gels. The discotic gels exhibit hole mobilities
      higher than those of the liquid crystal alone. Chemical modification of gelators
      with functional moieties is another versatile approach for functionalization of
      LC gels. Hydrogen-bonded gelators with photoswitchable azobenzene moieties have
      been developed and complexed with liquid crystals. The resultant photoresponsive
      LC gels show light-induced structural changes, which are applicable to rewritable
      information recording.

PMID- 22160341
TI  - Dendritic gelators.
AB  - Dendritic molecules fall somewhere between small-molecule organic systems and
      polymers. Like polymers, they are constructed from a repeating motif, often have
      nanoscopic dimensions, and are capable of forming multiple non-covalent
      interactions. However, they are synthesized using organic chemistry methods and,
      unlike polymers, have well-defined, discrete structures which can be precisely
      controlled. This combination of properties makes dendritic molecules of
      particular interest for application in the assembly of gel-phase materials. In
      particular, this review focusses on the way in which molecular-scale information,
      put into place using organic synthesis, is transcribed up to the nanoscale, as
      visualised by electron microscopy techniques. Furthermore, it is illustrated that
      the molecular and nanoscale structures have a direct impact on the macroscopic
      materials properties of the gel-phase network. We discuss the structural effects
      on macroscopic gelation in terms of molecular size, shape and chirality, and
      clearly outline the specific advantages of using dendritic structures for this
      type of soft materials application.

PMID- 22160342
TI  - Plicae palmatae of the cervical canals in uterus didelphys: MR imaging.
AB  - The plicae palmatae are normal endocervical folds on the anterior and posterior
      walls. The median longitudinal ridges of the plicae palmatae have been considered
      to represent a remnant of fused Mullerian ducts. We present a case of uterus
      didelphys in which the longitudinal ridge of the plicae palmatae were obviously
      demonstrated on both of the uterine cervices on axial T2-weighted image. The
      observation of the plicae palmatae on the duplicated uterine cervices indicates
      the plicae palmatae is an inherent structure of the cervical canal, not a remnant
      of fused Mullerian duct.

PMID- 22160343
TI  - Stereoselective bioreduction of 1-(4-methoxyphenyl)ethanone by whole cells of
      marine-derived fungi.
AB  - Nine strains of marine-derived fungi (Aspergillus sydowii Ce15, A. sydowii Ce19,
      Aspergillus sclerotiorum CBMAI 849, Bionectria sp. Ce5, Beauveria felina CBMAI
      738, Cladosporium cladosporioides CBMAI 857, Mucor racemosus CBMAI 847,
      Penicillium citrinum CBMAI 1186, and Penicillium miczynskii Gc5) were screened,
      catalyzing the asymmetric bioreduction of 1-(4-methoxyphenyl)ethanone 1 to its
      corresponding 1-(4-methoxyphenyl)ethanol 2. A. sydowii Ce15 and Bionectria sp.
      Ce5 produced the enantiopure (R)-alcohol 2 (>99% ee) in accordance with the anti
      Prelog rule and, the fungi B. felina CBMAI 738 (>99% ee) and P. citrinum CBMAI
      1186 (69% ee) in accordance with the Prelog rule. Stereoselective bioreduction by
      whole cells of marine-derived fungi described by us is important for the
      production of new reductases from marine-derived fungi.

PMID- 22160344
TI  - Detection of bioactive exometabolites produced by the filamentous marine
      cyanobacterium Geitlerinema sp.
AB  - Marine cyanobacteria are noted for their ability to excrete metabolites with
      biotic properties. This paper focuses on such exometabolites obtained from the
      culture of the marine filamentous cyanobacterium Geitlerinema sp. strain, their
      purification and subsequent analyses. By this means the recoveries of the active
      compounds, a prerequisite for properly determining their concentration, are
      quantified here for the first time. We demonstrate a new procedure using
      Amberlite XAD-1180 resin in combination with the eluent isopropanol for
      extraction of the culture media and gas chromatography as simplified chemical
      analysis. This procedure reduced necessary bacteria cultivation time (from 150 to
      21 days) at low volumes of culture media (300 mL) required for identification of
      two selected bioactive compounds: 4,4'-dihydroxybiphenyl and harmane.

PMID- 22160345
TI  - Proteomic strategy for identifying mollusc shell proteins using mild chemical
      degradation and trypsin digestion of insoluble organic shell matrix: a pilot
      study on Haliotis tuberculata.
AB  - A successful strategy for the identification of shell proteins is based on
      proteomic analyses where soluble and insoluble fractions isolated from organic
      shell matrix are digested with trypsin with the aim of generating peptides, which
      are used to identify novel shell proteins contained in databases. However, using
      trypsin as a sole degradative agent is limited by the enzyme's cleavage
      specificity and is dependent upon the occurrence of lysine and arginine in the
      shell protein sequence. To bypass this limitation, we investigated the ability of
      trifluoroacetic acid (TFA), a low-specificity chemical degradative agent, to
      generate clusters of analyzable peptides from organic shell matrix, suitable for
      database annotation. Acetic acid-insoluble fractions from Haliotis tuberculata
      shell were processed by trypsin followed by TFA digestion. The hydrolysates were
      used to annotate an expressed sequence tag library constructed from the mantle
      tissue of Haliotis asinina, a tropical abalone species. The characterization of
      sequences with repeat motifs featured in some of the shell matrix proteins
      benefited from TFA-induced serial cutting, which can result in peptide ladder
      series. Using the degradative specificities of TFA and trypsin, we were able to
      identify five novel shell proteins. This pilot study indicates that a mild
      chemical digestion of organic shell matrix combined with trypsin generates
      peptides suitable for proteomic analysis for better characterization of mollusc
      shell matrix proteins.

PMID- 22160346
TI  - Identification and characterization of piRNA-like small RNAs in the gonad of sea
      urchin (Strongylocentrotus nudus).
AB  - Piwi-interacting RNAs (piRNAs) and their partner PIWI proteins play an essential
      role in fertility, germline stem cell development, as well as the basic control
      and evolution of animal genomes. However, research was rare with regard to piRNA
      population in sea urchin, a model animal intensively used for development and
      genetics studies. Utilizing Solexa sequencing, we present an identification of
      13,051 piRNA-like RNAs expressed in male gonad of Strongylocentrotus nudus. Out
      of 202 tested RNAs, 94 sequences were confirmed to express in female gonad using
      microarray assay, suggesting that both male and female gonads are piRNA-like RNA
      enriched organs. These RNAs with "U" at the 5' end or "A" at position of 10, in
      size from 26 to 30 nucleotides, were predominantly 28 nt in length and tend to be
      clustered in small regions in genome, achieving the longest piRNA-like RNA
      enriched region about 5.5 kb in scaffold78427. Alignment results showed 11 RNAs
      were homologous to the known piRNAs. Furthermore, BLASTn searching against sea
      urchin repeat element database showed these piRNA-like RNAs matched to 101 types
      of DNA transposons and retrotransposons, of which SPRP1, Harbinger-N2, piggyBac
      N10, SINE2-1, and piggyBac-N11 were the most frequent hit elements, suggesting a
      transposon silencing function of these piRNA-like RNAs.

PMID- 22160347
TI  - The home TEACCHing program for toddlers with autism.
AB  - The study evaluated the efficacy a parent training intervention for children with
      autism based on the TEACCH model. Twenty families were randomly assigned to the
      treatment or waitlist group. All families were compared at pre- and post
      treatment on formal dependent measures. Direct measures of behavior were compared
      across six matched pairs using a multiple baseline probe design. The results of
      the multiple baseline design showed robust support for improvement in child and
      parent behavior. Due to the sample size and short time frame, results of a
      repeated measures analysis of variance did not reach significance.

PMID- 22160348
TI  - Social support and well-being at mid-life among mothers of adolescents and adults
      with autism spectrum disorders.
AB  - The present study investigated the impact of social support on the psychological
      well-being of mothers of adolescents and adults with ASD (n = 269). Quantity of
      support (number of social network members) as well as valence of support
      (positive support and negative support) were assessed using a modified version of
      the "convoy model" developed by Antonucci and Akiyama (1987). Having a larger
      social network was associated with improvements in maternal well-being over an 18
      month period. Higher levels of negative support as well as increases in negative
      support over the study period were associated with increases in depressive
      symptoms and negative affect and decreases in positive affect. Social support
      predicted changes in well-being above and beyond the impact of child behavior
      problems. Implications for clinical practice are discussed.

PMID- 22160349
TI  - The novel object recognition memory: neurobiology, test procedure, and its
      modifications.
AB  - Animal models of memory have been considered as the subject of many scientific
      publications at least since the beginning of the twentieth century. In humans,
      memory is often accessed through spoken or written language, while in animals,
      cognitive functions must be accessed through different kind of behaviors in many
      specific, experimental models of memory and learning. Among them, the novel
      object recognition test can be evaluated by the differences in the exploration
      time of novel and familiar objects. Its application is not limited to a field of
      research and enables that various issues can be studied, such as the memory and
      learning, the preference for novelty, the influence of different brain regions in
      the process of recognition, and even the study of different drugs and their
      effects. This paper describes the novel object recognition paradigms in animals,
      as a valuable measure of cognition. The purpose of this work was to review the
      neurobiology and methodological modifications of the test commonly used in
      behavioral pharmacology.

PMID- 22160350
TI  - Phase II study of S-1 monotherapy in patients with previously treated, advanced
      non-small-cell lung cancer.
AB  - BACKGROUND: In this phase II clinical trial, we evaluated the efficacy and safety
      of S-1 monotherapy in patients with previously treated advanced non-small-cell
      lung cancer (NSCLC). We also measured plasma concentrations of 5-fluorouracil (5
      FU) and 5-chloro-2,4-dihydroxypyridine components of S-1 and examined correlation
      with effectiveness and toxicity. METHODS: S-1 was given orally at a dose of 80
      mg/m(2)/day for 14 consecutive days, followed by a 7-day rest period. This
      treatment course was repeated until disease progression or intolerable toxicity.
      RESULTS: We enrolled 30 patients. The response rate was 26.7% (8/30), and the
      disease control rate was 70% (21/30). Median progression-free survival (PFS) was
      3.1 months, and median overall survival (OS) was 11.2 months. Mutations in the
      epidermal growth factor receptor (EGFR) gene were analyzed in 27 patients. The
      response rate was higher in patients with mutant EGFR (50.0%) than in those with
      wild-type EGFR (11.8%, P = 0.0288). Median PFS was 4.8 and 2.5 months (P =
      0.038), and median OS was 22.4 and 8.4 months (P = 0.071). There was no grade 4
      toxicity in this study. Five patients had grade 3 non-hematologic toxicity, and
      there was a trend toward higher plasma concentrations of 5-FU in those patients
      than in another patients. CONCLUSIONS: S-1 monotherapy is effective and well
      tolerated treatment for previously treated advanced NSCLC.

PMID- 22160351
TI  - Association of PDE4B polymorphisms and schizophrenia in Northwestern Han Chinese.
AB  - The phosphodiesterase 4B (PDE4B) is a candidate susceptibility gene for
      schizophrenia (SCZ), interacting with DISC1, a known genetic risk factor for SCZ.
      To examine if variants within PDE4B gene are associated with SCZ in Northwestern
      Han Chinese, and if these effects vary in gender-specific subgroup, we analyzed
      20 SNPs, selected from previous studies and preliminary HapMap data analyses with
      minor allele frequency (MAF) >= 20%, in a cohort of 428 cases and 572 controls
      from genetically independent Northwestern Han Chinese. Single SNP association,
      haplotype association and sex-specific association analysis were performed. We
      found that rs472952 is significantly associated with SCZ and rs7537440 is
      associated with SCZ in females. Further analysis indicated that a haplotype block
      spanning PDE4B2 splice site is highly associated with SCZ and several haplotypes
      in this block have about twofold to threefold increase in cases. Our results
      provide further evidence that PDE4B may play important roles in the etiology of
      SCZ.

PMID- 22160352
TI  - Analysis of GABA-induced inhibition of spontaneous firing in chick accessory lobe
      neurons.
AB  - It has been hypothesized that chick accessory lobes (ALs) contain functional
      neurons and act as a sensory organ of equilibrium. It was reported that neurons
      located in an outer layer of ALs showed gamma-aminobutyric acid (GABA)- and
      glutamic acid decarboxylase (GAD)-like immunoreactivity more strongly than
      centrally located neurons, which were surrounded by the GAD-immunoreactive
      terminals. We investigated effects of GABA on the electrical activity of AL
      neurons. About 50% of embryonic AL neurons exhibited spontaneous firing. In the
      on-cell recording, GABA, muscimol, and GABA in combination with CGP35348
      inhibited this firing. In whole-cell voltage clamp recordings, GABA and muscimol
      evoked a transient current. The mean reversal potential of GABA-evoked currents
      was close to the theoretical reversal potential of Cl-. These results indicate
      that GABA exerts the inhibitory effect on the firing through the activation of
      GABA(A) receptors. In addition, the intracellular concentration of Cl- was
      estimated to be about 16 mM in measurements with the gramicidin-perforated
      configuration, indicating the physiological reversal potential of the GABA
      current was about -60 mV. In conclusion, AL neurons have an intrinsic mechanism
      to evoke the spontaneous firing, which can be arrested by the inhibitory
      mechanism through the activation of the GABA(A) receptors.

PMID- 22160353
TI  - Alternating from subtotal thyroid resection to total thyroidectomy in the
      treatment of Graves' disease prevents recurrences but increases the frequency of
      permanent hypoparathyroidism.
AB  - PURPOSE: This study aims to compare the results of three different surgical
      techniques in the treatment of Graves' disease. METHODS: All patients operated on
      due to Graves' disease at a single institution between 1985 and 2009 were
      followed up for a median time of 152 months. The same endocrine surgeon operated
      altogether 265 patients; 111 with bilateral subtotal thyroid resection, 65 with
      lobectomy + unilateral subtotal resection (Dunhill's operation) and 99 with total
      thyroidectomy. RESULTS: Recurrence of thyreotoxicosis was seen in 11 (9.9%)
      patients operated on with bilateral thyroid resection, in two (3.1%) of those
      operated on with Dunhill's method and in none treated with total thyroidectomy.
      Permanent hypoparathyroidism was observed in 6% of the patients with total
      thyroidectomy, in 0.9% of those operated with bilateral subtotal resection and in
      none of the patients with Dunhill's procedure (p < 0.001). The frequency of
      permanent paresis of one recurrent laryngeal nerve was 2%, 0% and 1.5%,
      respectively, in the three different groups. At follow-up, thyroxine
      supplementation therapy was given to 81 (73%) of the patients treated with
      bilateral subtotal resection, to 58 (89%) of those treated with Dunhill's
      operation and to all of those treated with total thyroidectomy. CONCLUSIONS: It
      is concluded that surgical treatment of Graves' disease with Dunhill's procedure,
      leaving a remnant of 1-2 g, seems to minimize the risks of both recurrences and
      permanent hypoparathyroidism.

PMID- 22160354
TI  - Extended and stable gene expression via nucleofection of MIDGE construct into
      adult human marrow mesenchymal stromal cells.
AB  - Human mesenchymal stromal cell (hMSC) is a potential target for cell and gene
      therapy-based approaches against a variety of different diseases. Whilst cationic
      lipofection has been widely experimented, the Nucleofector technology is a
      relatively new non-viral transfection method designed for primary cells and hard
      to-transfect cell lines. Herein, we compared the efficiency and viability of
      nucleofection with cationic lipofection, and used the more efficient transfection
      method, nucleofection, to deliver a construct of minimalistic, immunologically
      defined gene expression encoding the erythropoietin (MIDGE-EPO) into hMSC. MIDGE
      construct is relatively safer than the viral and plasmid expression systems as
      the detrimental eukaryotic and prokaryotic gene and sequences have been
      eliminated. Using a plasmid encoding the luciferase gene, we demonstrated a high
      transfection efficiency using the U-23 (21.79 +/- 1.09%) and C-17 (5.62 +/-
      1.09%) pulsing program in nucleofection. The cell viabilities were (44.93 +/-
      10.10)% and (21.93 +/- 5.72)%, respectively 24 h post-nucleofection. On the other
      hand, lipofection treatment only yielded less than 0.6% efficiencies despite
      showing higher viabilities. Nucleofection did not affect hMSC renewability,
      immunophenotype and differentiation potentials. Subsequently, we nucleofected
      MIDGE-EPO using the U-23 pulsing program into hMSC. The results showed that,
      despite a low nucleofection efficiency with this construct, the EPO protein was
      stably expressed in the nucleofected cells up to 55 days when determined by ELISA
      or immunocytochemical staining. In conclusion, nucleofection is an efficient non
      viral transfection approach for hMSC, which when used in conjunction with a MIDGE
      construct, could result in extended and stable transgene expression in hMSC.

PMID- 22160355
TI  - Liver-specific contrast agent-enhanced magnetic resonance and 18F
      fluorodeoxyglucose positron emission tomography findings of hepatocellular
      adenoma: report of a case.
AB  - We report a case of hepatocellular adenoma, focusing on the findings of liver
      specific contrast agent-enhanced magnetic resonance imaging (MRI) and 18F
      fluorodeoxyglucose positron emission tomography (FDG-PET). The patient was a 37
      year-old woman, referred to us after contrast-enhanced computed tomography showed
      a homogeneous, poorly enhanced liver tumor, 2.8 cm in diameter. Magnetic
      resonance imaging showed a liver mass with significant fatty change. The tumor
      increased in size to 3.3 cm over 9 months of follow-up. Gadolinium-ethoxybenzyl
      diethylenetriamine penta-acetic acid-enhanced MRI revealed spotty enhancement in
      the hypointense tumor in the hepatobiliary phase. Subsequent FDG-PET showed
      increased uptake of FDG (maximum standardized uptake value 5.0), which suggested
      the possibility of malignancy. The patient underwent partial hepatectomy, and
      histological examination of the resected specimen revealed a tumor composed of
      hepatocyte-like cells with minimal cellular atypia and significant diffuse fatty
      change. Based on these findings, we diagnosed hepatocellular adenoma.

PMID- 22160356
TI  - Huge inflammatory pseudotumor of the spleen with postoperative portal vein
      thrombosis: report of a case.
AB  - We report the rare case of a splenic inflammatory pseudotumor associated with
      massive splenomegaly, diagnosed after surgery. A 51-year-old woman was admitted
      to our hospital for investigation of anemia. Physical examination revealed a
      palpable left upper quadrant mass. Computed tomography and magnetic resonance
      imaging showed a splenic mass, 20 cm in diameter. We performed splenectomy for
      both diagnosis and treatment. The spleen weighed 2400 g, and histologic
      examination of the mass confirmed an inflammatory pseudotumor. Portal vein
      thrombosis (PVT) developed the day after surgery, but resolved with
      anticoagulation therapy. This case highlights that there is a risk of PVT after
      splenectomy in patients with massive splenomegaly, and that anticoagulant therapy
      should be initiated promptly.

PMID- 22160357
TI  - Sarcoid-like reaction in breast cancer: a long-term follow-up series of eight
      patients.
AB  - PURPOSE: Finding an intrathoracic or axillary mass in a breast cancer patient
      should raise suspicion of a pulmonary or mediastinal nodal metastasis or axillary
      recurrence. Surprisingly, noncaseating epithelioid cell granuloma can be found in
      this type of lesion, as in sarcoidosis or a sarcoid-like reaction. METHODS: This
      series included eight breast cancer patients in whom a late sarcoid-like reaction
      developed: as an intrathoracic lesion in six, and as an ipsilateral axillary
      lesion in two. The latency period from oncological surgery to the diagnosis of
      sarcoidosis was 40 months and the average follow-up after the diagnosis of
      sarcoidosis was 63.38 months. RESULTS: None of the patients suffered relapse or
      oncological events during the period of this study. CONCLUSION: To avoid
      misdiagnosis and overtreatment, pathological examination should always be carried
      out. We do not recommend any specific treatment for sarcoidosis in a breast
      cancer patient, but routine oncological follow-up is appropriate. A larger series
      with statistical analysis is necessary to evaluate the prognosis.

PMID- 22160358
TI  - True left-sided gallbladder with a portal anomaly: report of a case.
AB  - A 65-year-old female who presented with back pain was diagnosed to have the
      presence of biliary sludge in the gallbladder. Computed tomography showed that
      the round ligament connected to the left portal umbilical portion was in the
      normal anatomical position. However, the gallbladder was located to the left of
      the middle hepatic vein and the round ligament, attached to the left lateral
      segment of the liver. The right posterior portal vein diverged alone from the
      main portal vein, and there was a long stem from the right anterior and left
      portal veins. Laparoscopic cholecystectomy confirmed the abnormal location of the
      gallbladder. Most reported cases of left-sided gallbladder are caused by a right
      sided round ligament, which is called a "false" left-sided gallbladder. A case of
      left-sided gallbladder with a normal left-sided round ligament, which is
      designated as a case of "true" left-sided gallbladder, is extremely rare.

PMID- 22160359
TI  - Sexual dimorphism of femoral neck cross-sectional bone geometry in athletes and
      non-athletes: a hip structural analysis study.
AB  - The characterisation of bone geometry in male and female athletes may increase
      our understanding of how physical loading may enhance bone strength in both
      sexes. This study investigated sexual dimorphism in hip geometry of athletes and
      age- and sex-matched non-athletes. Dual energy X-ray absorptiometry of the left
      proximal femur was performed in 62 male (n = 31; 30.2 +/- 4.6 years) and female
      (n = 31; 27.9 +/- 5.2 years) competitive endurance runners, and 36 male (n = 18;
      28.7 +/- 5.8 years) and female (n = 18; 29.1 +/- 5.3 years) non-athletes. The hip
      structural analysis programme determined areal bone mineral density (aBMD), bone
      area (BA), hip axis length, cross-sectional area (CSA), and cross-sectional
      moment of inertia (CSMI) of the femoral neck. Strength indices were derived from
      the femoral strength index (FSI) (Yoshikawa et al., J Bone Miner Res 9:1053-1064,
      1994). Despite similar size-adjusted aBMD, sexual dimorphism was apparent for BA,
      CSA and CSMI, with superior values in men compared to women (P < 0.01). FSI was
      greater in male and female athletes than non-athletes (P < 0.01). From all
      groups, results in male athletes inferred greatest resistance to axial (CSA) and
      bending loads (FSI). Estimates of bone strength (FSI) were greater in female
      athletes than male and female non-athletes, supporting the osteogenic value of
      regular loading of the hip.

PMID- 22160361
TI  - New spectrofluorimetric method for determination of cephalosporins in
      pharmaceutical formulations.
AB  - Simple, accurate and sensitive spectrofluorimetric method has been proposed for
      the determination of three cephalosporins, namely; cefixime (cefi), cephalexine
      (ceph), cefotaxime sodium (cefo) in pharmaceutical formulations. The method is
      based on a reaction between cephalosporins with 1, 2-naphthoquinone-4-sulfonic
      (NQS) in alkaline medium, at pH values of 12.0 for cefi and 13.0 for ceph and
      cefo to give highly fluorescent derivatives extracted with chloroform and
      subsequently measured at 600,580 and 580 nm after excitation at 520,455 and 490
      nm for cefi, ceph and cefo respectively. The optimum experimental conditions have
      been studied. Beer's law is obeyed over the concentrations of 10-35 ng/mL, 10-60
      ng/mL and 20-45 ng/mL for cefi,ceph and cefo, respectively. The detection limits
      were 2.02 ng/mL, 2.09 ng/mL and 2.30 ng/mL for cefi, ceph and cefo, respectively,
      with a linear regression correlation coefficient of 0.9987, 0.9995 and 0.9991 and
      recoveries in range from 98.5-107.04, 95.17-101.00 and 95.00-109.55% for cefi,
      ceph and cefo, respectively. This method is simple and can be applied for the
      determination of cefi, ceph and cefo in pharmaceutical formulations in quality
      control laboratories.

PMID- 22160360
TI  - Entorhinal verrucae geometry is coincident and correlates with Alzheimer's
      lesions: a combined neuropathology and high-resolution ex vivo MRI analysis.
AB  - Entorhinal cortex displays a distinctive organization in layer II and forms small
      elevations on its surface called entorhinal verrucae. In Alzheimer's disease, the
      verrucae disappear due to neurofibrillary tangle formation and neuronal death.
      Isosurface models were reconstructed from high-resolution ex vivo MRI volumes
      scanned at 7.0 T and individual verruca were measured quantitatively for height,
      width, volume, and surface area on control and mild Alzheimer's cases. Mean
      verruca height was 0.13 +/- 0.04 mm for our cognitively normal (controls) sample
      set whereas for mild AD samples mean height was 0.11 mm +/- 0.05 mm (p < 0.001)
      in entorhinal cortex (n = 10 cases). These quantitative methods were validated by
      a significant correlation of verrucae height and volume with qualitative verrucae
      ratings (n = 36 cases). Entorhinal surfaces were significantly different from
      other cortical heights such as, cingulate, frontal, occipital, parietal and
      temporal cortices. Colocalization of verrucae with entorhinal islands was
      confirmed in ex vivo MRI and, moreover, verrucae ratings were negatively
      correlated to Braak and Braak pathological stage. This study characterizes novel
      methods to measure individual entorhinal verruca size, and shows that verrucae
      size correlates to Alzheimer's pathology. Taken together, these results suggest
      that verrucae may have the potential to serve as an early and specific
      morphological marker for mild cognitive impairment and Alzheimer's disease.

PMID- 22160362
TI  - Mining of miRNAs and potential targets from gene oriented clusters of transcripts
      sequences of the anti-malarial plant, Artemisia annua.
AB  - miRNAs involved in the biosynthesis of artemisinin, an anti-malarial compound
      form the plant Artemisia annua, have been identified using computational
      approaches to find conserved pre-miRNAs in available A. annua UniGene
      collections. Eleven pre-miRNAs were found from nine families. Targets predicted
      for these miRNAs were mainly transcription factors for conserved miRNAs. No
      target genes involved in artemisinin biosynthesis were found. However, miR390 was
      predicted to target a gene involved in the trichome development, which is the
      site of synthesis of artemisinin and could be a candidate for genetic
      transformation aiming to increase the content of artemisinin. Phylogenetic
      analyses were carried out to determinate the relation between A. annua and other
      plant pre-miRNAs: the pre-miRNA-based phylogenetic trees failed to correspond to
      known phylogenies, suggesting that pre-miRNA primary sequences may be too
      variable to accurately predict phylogenetic relations.

PMID- 22160363
TI  - Fibroblast growth factor 2-functionalized collagen matrices for skeletal muscle
      tissue engineering.
AB  - Fibroblast growth factor 2 (FGF2) protein plays important roles in wound healing
      and tissue regeneration. Collagen is clinically used for wound care applications.
      We investigated the potential value of FGF2-functionalized collagen matrices for
      skeletal muscle tissue engineering. When C2C12 cells were treated with FGF2, cell
      adhesion increased after 3 and 5 days compared to the control (P < 0.05). Wound
      healing activity of FGF2 was slightly higher than the control through cell
      migration. Cell proliferation activity of FGF2-functionalized collagen matrices
      on C2C12 cells also increased. Taken together, FGF2 stimulated C2C12 myoblast
      growth by promoting cell adhesion, proliferation and wound healing activity after
      injury. The potential effect of FGF2-functionalized collagen matrices was also
      observed. Thus FGF2 stimulates skeletal muscle development and regeneration,
      thereby leading to potential utility for skeletal muscle tissue engineering.

PMID- 22160364
TI  - PolyA RT-PCR-based quantification of microRNA by using universal TaqMan probe.
AB  - Quantification of microRNAs (miRNAs) in tissues under normal and pathological
      conditions is important for elucidating miRNA functions. Based on a PolyA RT-PCR
      method we have described (J Zhang et al. Biochem Biophys Res Commun 2008 377:136
      140), a modified miRNA quantification method was developed and validated using a
      universal TaqMan probe complementary to the reverse transcript primer. This
      method effectively detects miRNA expression in cell lines and tissues. The TaqMan
      probe is more accurate and reliable than the SYBR Green method since it was free
      from primer dimers. A series of miRNAs were tested in five different mouse
      tissues: the method differentiated different miRNAs of the same family. This
      universal TaqMan probe-based PolyA RT-PCR method showed its advantages in
      precision, simplicity and high-throughput capability compared with other miRNA
      detecting methods.

PMID- 22160365
TI  - Application of PVA-derived porous media to accelerate biodegradation (composting)
      of organic solid substrates.
AB  - Poly(vinyl alcohol) (PVA)-derived cubes with fine pores and high water-binding
      and microbial adhesion capacities, enhanced the biodegradation of organic solid
      substrates with the temperature of the mixture increasing to over 65 degrees C on
      the second day and being maintained ~60 degrees C for the following 3 days,
      averaging at least 15 degrees C higher than the control. The amount of CO(2)
      evolved also reflected a higher level of biodegradation. The compost made with
      PVA porous cubes for 2 weeks improved lettuce cultivation and crop losses
      decreased by at least 10% compared with the control. Thus PVA porous cubes can
      facilitate the production of mature compost for plants.

PMID- 22160366
TI  - Enhancing acid tolerance of Leuconostoc mesenteroides with glutathione.
AB  - Leuconostoc mesenteroides is a commercially important lactic acid bacterium
      currently used as a starter for kimchi and kefir. However, its sensitivity to
      acid stress limits its performance. L. mesenteroides was grown in a medium
      supplemented with 3.2 or 6.4 mM glutathione (GSH), and cell survival rates were
      measured during a long-term mild acid challenge (pH 4.0). As a result, GSH was
      imported by the cells and protected against acid stress; thereafter it was
      consumed as a nutrient. Acid stress resistance of starter cultures of this
      bacterium can thus be improved by cultivating it in media supplemented with GSH.

PMID- 22160367
TI  - Polyamines increase carpospore output and growth during in vitro cultivation of
      Hydropuntia cornea.
AB  - Carpospore output and development in the marine red alga Hydropuntia cornea J.
      Agardh. were increased by adding polyamines (PAs) (putrescine, spermidine and
      spermine) singly or in combinations at 10(-9), 10(-6) and 10(-3) M. Cell
      divisions after spore release and development of apical axis between 17 and 21
      days characterized carpospore development. PAs increased carpospore development
      by promoting cell divisions to form cell masses between day 2 and 3.
      Morphogenesis to develop apical axes occurred at day 7. Spermine at 10(-6) M and
      a combination of putrescine 10(-9) M + spermidine 10(-9) M + spermine 10(-9) M
      gave a higher number of carpospores and enhanced their further development to
      sporelings.

PMID- 22160368
TI  - Polymorphic NumtS trace human population relationships.
AB  - The human genome is constantly subjected to evolutionary forces which shape its
      architecture. Insertions of mitochondrial DNA sequences into nuclear genome
      (NumtS) have been described in several eukaryotic species, including Homo sapiens
      and other primates. The ongoing process of the generation of NumtS has made them
      valuable markers in primate phylogenetic studies, as well as potentially
      informative loci for reconstructing the genetic history of modern humans. Here,
      we report the identification of 53 human-specific NumtS by inspection of the UCSC
      genome browser, showing that they may be direct insertions of mitochondrial DNA
      into the human nuclear DNA after the human-chimpanzee split. In silico analyses
      allowed us to identify 14 NumtS which are polymorphic in terms of their
      presence/absence within the human genome in individuals of different ancestry.
      The allele frequencies of these polymorphic NumtS were calculated for 1000
      Genomes Project sequence data from 13 populations worldwide, and principal
      components analysis and hierarchical clustering methods allowed the detection of
      strong signals of geographical structure related to the genetic diversity of
      these loci. All identified polymorphic human-specific NumtS together with a
      tandemly duplicated NumtS have also been validated by PCR amplification on a
      panel of 60 samples belonging to five native populations worldwide, confirming
      the expected NumtS variability. On the basis of these findings, we have succeeded
      in depicting the landscape of variation of a series of NumtS in several ethnic
      groups, making an advance in their identification as useful markers in the study
      on human population genetics.

PMID- 22160369
TI  - Training increases peroxiredoxin 2 contents in the erythrocytes of
      overweight/obese men suffering from type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is associated with an increased release of free
      radicals which play an important role in the manifestation of diabetes and in the
      progression of diabetic complications. Peroxiredoxins are thought to be essential
      components of the erythrocyte antioxidative defense. Therefore, we compared
      peroxiredoxin isoform contents (PRDX1-6 immuno-histochemial stainings) in the
      erythrocytes of overweight/obese T2DM men (n = 6) and of BMI-matched non-diabetic
      male control subjects (n = 6). Only erythrocyte PRDX1 and PRDX2 proteins were
      detectable using immunohistochemical methods. PRDX1 was significantly increased
      in T2DM men relative to control subjects (+95.9%, P <= 0.05). Furthermore, we
      studied the influence of a 3-month endurance training program (3 times a week,
      cycling at 75% maximal heart rate) on erythrocyte PRDX1 and PRDX2 contents in
      overweight/obese T2DM men (n = 11). Training significantly increased PRDX2 at
      rest (+96%, P <= 0.05). The up-regulation of the peroxiredoxin system may help
      counteract free radicals in the erythrocytes of T2DM patients.

PMID- 22160370
TI  - Prevalence and correlates of screen-based media use among youths with autism
      spectrum disorders.
AB  - Anecdotal reports indicate that individuals with autism spectrum disorders (ASD)
      are often preoccupied with television, computers, and video games (screen-based
      media). However, few studies have examined this issue. The current study examined
      screen-based media use among a large, nationally representative sample of youths
      participating in the National Longitudinal Transition Study-2 (NLTS2). The
      majority of youths with ASD (64.2%) spent most of their free time using non
      social media (television, video games), while only 13.2% spent time on social
      media (email, internet chatting). Compared with other disability groups
      (speech/language impairments, learning disabilities, intellectual disabilities),
      rates of non-social media use were higher among the ASD group, and rates of
      social media use were lower. Demographic and symptom-specific correlates were
      also examined.

PMID- 22160371
TI  - Just another social scene: evidence for decreased attention to negative social
      scenes in high-functioning autism.
AB  - The adaptive threat-detection advantage takes the form of a preferential
      orienting of attention to threatening scenes. In this study, we compared
      attention to social scenes in 15 high-functioning individuals with autism (ASD)
      and matched typically developing (TD) individuals. Eye-tracking was recorded
      while participants were presented with pairs of scenes, either emotional positive
      neutral, emotional negative-neutral or neutral-neutral scenes. Early allocation
      of attention, the first image fixated in each pair, differed between groups:
      contrary to TD individuals who showed the typical threat-detection advantage
      towards negative images, the ASD group failed to show a bias toward threat
      related scenes. Later processing of stimuli, indicated by the total fixation to
      the images during the 3-s presentation, was found unaffected in the ASD group.
      These results support the hypothesis of an early atypical allocation of attention
      towards natural social scenes in ASD, that is compensated in later stages of
      visual processing.

PMID- 22160372
TI  - Transcriptomic characterization of the larval stage in gilthead seabream (Sparus
      aurata) by 454 pyrosequencing.
AB  - Gilthead seabream (Sparus aurata) is a teleost belonging to the family Sparidae
      with a high economical relevance in the Mediterranean countries. Although genomic
      tools have been developed in this species in order to investigate its physiology
      at the molecular level and consequently its culture, genomic information on post
      embryonic development is still scarce. In this study, we have investigated the
      transcriptome of a marine teleost during the larval stage (from hatching to 60
      days after hatching) by the use of 454 pyrosequencing technology. We obtained a
      total of 68,289 assembled contigs, representing putative transcripts, belonging
      to 54,606 different clusters. Comparison against all S. aurata expressed
      sequenced tags (ESTs) from the NCBI database revealed that up to 34,722 contigs,
      belonging to about 61% of gene clusters, are sequences previously not described.
      Contigs were annotated through an iterative Blast pipeline by comparison against
      databases such as NCBI RefSeq from Danio rerio, SwissProt or NCBI teleost ESTs.
      Our results indicate that we have enriched the number of annotated sequences for
      this species by more than 50% compared with previously existing databases for the
      gilthead seabream. Gene Ontology analysis of these novel sequences revealed that
      there is a statistically significant number of transcripts with key roles in
      larval development, differentiation, morphology, and growth. Finally, all
      information has been made available online through user-friendly interfaces such
      as GBrowse and a Blast server with a graphical frontend.

PMID- 22160373
TI  - Crohn's disease: prevalence of intestinal and extraintestinal manifestations
      detected by computed tomography enterography with water enema.
AB  - BACKGROUND: Computed tomography enterography (CTE) may detect the presence,
      severity, and extent of bowel inflammation in patients with Crohn's disease (CD).
      The aim of our study was to assess, among a cohort of 22 histologically proven CD
      patients, the prevalence of disease distribution, behavior, anastomotic
      recurrence and extraintestinal manifestations detected by an original CTE
      technique. METHODS: Two radiologists reviewed 221 CTEs performed providing both
      small and large bowel distension by oral administration of neutral contrast
      material and trans-rectal introduction of a water enema (CTE-WE). RESULTS: Ileal
      CD was detected in 116 CTE-WEs (52.4%), including 71/116 (61.2%) non
      stricturing/non-penetrating, 17/116 (14.6%) stricturing, and 28/116 (24.1%)
      penetrating forms. Colonic CD was appreciable in 35 (15.8%) patients, including
      18/35 (51.4%) non-stricturing/non-penetrating, 6/35 (17.1%) stricturing, and
      11/35 (31.4%) penetrating forms. Ileocolic CD was present in 52 (23.5%) CTE-WEs,
      including 30/52 (57.7%) non-stricturing/ non-penetrating; 3/52 (5.7%)
      stricturing, and 19/52 (36.5%) penetrating forms. In 10/221 patients (4.5%),
      upper gastrointestinal involvement (UGI) was present. Perianal disease was
      observed in 17/221 patients (7.7%). Fistulas were present in 52 (23.5%) and
      abscesses in 24 (10.8%) CTE-WEs, respectively. Among 57/221 (25.8%) patients who
      had undergone a disease-related intestinal resection, in 30/57 cases (52.6%) CD
      recurrence at the anastomosis was present. 4/221 patients (1.8%) with a
      histologically confirmed intestinal neoplastic stenosis were observed.
      Sacroiliitis (24%) was found to be prevalent over hepatic steatosis (10.8%),
      cholelithiasis (8.6%), and nephrolithiasis (4%). CONCLUSIONS: CTE-WE represents a
      comprehensive imaging technique which may demonstrate bowel inflammation and CD
      extraintestinal manifestations. A peculiar prevalence of UGI involvement and
      neoplastic strictures were observed. In our study the prevalence of sacroiliitis
      resulted higher than previously reported.

PMID- 22160375
TI  - Effect of natalizumab on clinical and radiological disease activity in a French
      cohort of patients with relapsing-remitting multiple sclerosis.
AB  - "Disease activity free" in relapsing-remitting multiple sclerosis (RRMS) is a new
      concept introduced by the results of the AFFIRM study. Our objective was to
      analyze the clinical and radiological efficacy of natalizumab treatment in actual
      clinical practice and compare it with the post hoc analysis of the AFFIRM study.
      All patients with RRMS who began treatment with natalizumab at our two French MS
      centres between April 2007 and May 2008 were included and followed-up for at
      least 2 years. No measurable disease activity ("disease activity free") was
      defined as no activity on clinical measures (no relapses and no sustained
      disability progression) and radiological measures (no gadolinium-enhancing
      lesions and no new T2-hyperintense lesions on cerebral MRI). A total of 193
      patients were included. Natalizumab was discontinued in 25.9% of cases before the
      completion of 2 years of treatment. In our cohort, we observed patients with more
      severe disease than in the AFFIRM study. The proportion of patients remaining
      free of clinical activity during 2 years of treatment was lower than in the
      AFFIRM study (37.8% vs. 64.3%). The proportion of patients remaining free of
      radiological activity during 2 years of treatment was higher than in the AFFIRM
      study (68.9% vs. 57.7%), while the proportion of patients remaining free of
      disease activity during 2 years of treatment was comparable to the AFFIRM study
      (33.3% vs. 36.7%). Natalizumab seems to be as effective in a real-life setting as
      in pivotal and post hoc studies. The confirmation of such benefits is important
      because of the progressive multifocal leukoencephalopathy risk.

PMID- 22160374
TI  - Colonization, pathogenicity, host susceptibility, and therapeutics for
      Staphylococcus aureus: what is the clinical relevance?
AB  - Staphylococcus aureus is a human commensal that can also cause a broad spectrum
      of clinical disease. Factors associated with clinical disease are myriad and
      dynamic and include pathogen virulence, antimicrobial resistance, and host
      susceptibility. Additionally, infection control measures aimed at the
      environmental niches of S. aureus and therapeutic advances continue to impact
      upon the incidence and outcomes of staphylococcal infections. This review article
      focuses on the clinical relevance of advances in our understanding of
      staphylococcal colonization, virulence, host susceptibility, and therapeutics.
      Over the past decade key developments have arisen. First, rates of nosocomial
      methicillin-resistant S. aureus (MRSA) infections have significantly declined in
      many countries. Second, we have made great strides in our understanding of the
      molecular pathogenesis of S. aureus in general and community-associated MRSA in
      particular. Third, host risk factors for invasive staphylococcal infections, such
      as advancing age, increasing numbers of invasive medical interventions, and a
      growing proportion of patients with healthcare contact, remain dynamic. Finally,
      several new antimicrobial agents active against MRSA have become available for
      clinical use. Humans and S. aureus co-exist, and the dynamic interface between
      host, pathogen, and our attempts to influence these interactions will continue to
      rapidly change. Although progress has been made in the past decade, we are likely
      to face further surprises such as the recent waves of community-associated MRSA.

PMID- 22160377
TI  - EGFL7: a unique angiogenic signaling factor in vascular development and disease.
AB  - EGFL7 is a secreted angiogenic factor that is highly conserved in vertebrates.
      Most secreted angiogenic signaling molecules, including VEGF and fibroblast
      growth factor-2, are mainly expressed by non-endothelial cell types such as
      fibroblasts. In contrast, EGFL7 is unique because it is almost exclusively
      expressed by and acts on endothelial cells. Egfl7 expression is highest when the
      endothelium is in an active, proliferating state. This factor acts as a
      chemoattractant for endothelial cells and binds to components of the
      extracellular matrix. In vivo, Egfl7 is important for regulating tubulogenesis in
      zebrafish and for controlling vascular patterning and integrity in mice. Its
      function in blood vessel development is mediated, at least in part, through
      modulation of Notch signaling. In this review, we summarize the findings that
      support a role for Egfl7 in developmental and postnatal angiogenesis and describe
      the EGFL7-signaling pathways that underlie these processes. In addition, we
      discuss a potential role for EGFL7 in vascular repair and its possible use as a
      therapeutic target for treatment of hypoxia-induced injury. Finally, we consider
      EGFL7 action during tumorigenesis and its potential as an antiangiogenic agent.

PMID- 22160378
TI  - KIT with D816 mutations cooperates with CBFB-MYH11 for leukemogenesis in mice.
AB  - KIT mutations are the most common secondary mutations in inv(16) acute myeloid
      leukemia (AML) patients and are associated with poor prognosis. It is therefore
      important to verify that KIT mutations cooperate with CBFB-MYH11, the fusion gene
      generated by inv(16), for leukemogenesis. Here, we transduced wild-type and
      conditional Cbfb-MYH11 knockin (KI) mouse bone marrow (BM) cells with KIT D816V/Y
      mutations. KIT transduction caused massive BM Lin(-) cell death and fewer
      colonies in culture that were less severe in the KI cells. D816Y KIT but not wild
      type KIT enhanced proliferation in Lin(-) cells and led to more mixed lineage
      colonies from transduced KI BM cells. Importantly, 60% and 80% of mice
      transplanted with KI BM cells expressing D816V or D816Y KIT, respectively, died
      from leukemia within 9 months, whereas no control mice died. Results from
      limiting dilution transplantations indicate higher frequencies of leukemia
      initiating cells in the leukemia expressing mutated KIT. Signaling pathway
      analysis revealed that p44/42 MAPK and Stat3, but not AKT and Stat5, were
      strongly phosphorylated in the leukemia cells. Finally, leukemia cells carrying
      KIT D816 mutations were sensitive to the kinase inhibitor PKC412. Our data
      provide clear evidence for cooperation between mutated KIT and CBFB-MYH11 during
      leukemogenesis.

PMID- 22160379
TI  - Histone deacetylase inhibitors are potent inducers of gene expression in latent
      EBV and sensitize lymphoma cells to nucleoside antiviral agents.
AB  - Induction of EBV lytic-phase gene expression, combined with exposure to an
      antiherpes viral drug, represents a promising targeted therapeutic approach to
      EBV-associated lymphomas. Short-chain fatty acids or certain chemotherapeutics
      have been used to induce EBV lytic-phase gene expression in cultured cells and
      mouse models, but these studies generally have not translated into clinical
      application. The recent success of a clinical trial with the pan-histone
      deacetylase (pan-HDAC) inhibitor arginine butyrate and the antiherpes viral drug
      ganciclovir in the treatment of EBV lymphomas prompted us to investigate the
      potential of several HDAC inhibitors, including some new, highly potent
      compounds, to sensitize EBV(+) human lymphoma cells to antiviral agents in vitro.
      Our study included short-chain fatty acids (sodium butyrate and valproic acid);
      hydroxamic acids (oxamflatin, Scriptaid, suberoyl anilide hydroxamic acid,
      panobinostat [LBH589], and belinostat [PXD101]); the benzamide MS275; the cyclic
      tetrapeptide apicidin; and the recently discovered HDAC inhibitor largazole. With
      the exception of suberoyl anilide hydroxamic acid and PXD101, all of the other
      HDAC inhibitors effectively sensitized EBV(+) lymphoma cells to ganciclovir.
      LBH589, MS275, and largazole were effective at nanomolar concentrations and were
      10(4) to 10(5) times more potent than butyrate. The effectiveness and potency of
      these HDAC inhibitors make them potentially applicable as sensitizers to
      antivirals for the treatment of EBV-associated lymphomas.

PMID- 22160380
TI  - Safety of anticoagulants in children with arterial ischemic stroke.
AB  - Pediatric arterial ischemic stroke (AIS) is increasingly diagnosed and carries
      significant risks of recurrence, morbidity, and mortality. Anticoagulant therapy
      (ACT) is commonly prescribed in childhood AIS. Hemorrhagic complication rates in
      pediatric stroke are unknown, and adult safety data are of limited applicability.
      We analyzed a prospectively enrolled cohort of children (aged 1 month-18 years)
      with acute AIS selected using standardized criteria for protocol-based ACT over
      14-year period. We assessed ACT-associated intracranial hemorrhage (ICH),
      including frequency, clinical and radiologic characteristics, predictors, and
      outcome. Among 215 children with AIS, 123 received ACT within 7 days after
      diagnosis. During anticoagulation, 14 (11%) children developed new or increased
      ICH, all within 26 days from diagnosis. ICH was symptomatic in 5 (4%),
      asymptomatic in 9 (7%), and mild (European Cooperative Acute Stroke Study grades
      HI1 or HI2) in all but 1 child (ECASS PH-2). Long-term neurologic outcomes after
      ACT-associated ICH in survivors were abnormal in 73% (8/11). Comparably, 12 of 75
      (16%) children treated without anticoagulation developed new or increased ICH on
      follow-up imaging (P = .3507). We conclude that ACT is relatively safe in
      children with AIS, with a 4% risk of symptomatic ICH. Based on the safety of ACT
      in our study, clinical trials of ACT in childhood AIS are warranted.

PMID- 22160381
TI  - Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral
      decitabine.
AB  - The deoxycytidine analog decitabine (DAC) can deplete DNA methyl-transferase 1
      (DNMT1) and thereby modify cellular epigenetics, gene expression, and
      differentiation. However, a barrier to efficacious and accessible DNMT1-targeted
      therapy is cytidine deaminase, an enzyme highly expressed in the intestine and
      liver that rapidly metabolizes DAC into inactive uridine counterparts, severely
      limiting exposure time and oral bioavailability. In the present study, the
      effects of tetrahydrouridine (THU), a competitive inhibitor of cytidine
      deaminase, on the pharmacokinetics and pharmacodynamics of oral DAC were
      evaluated in mice and nonhuman primates. Oral administration of THU before oral
      DAC extended DAC absorption time and widened the concentration-time profile,
      increasing the exposure time for S-phase-specific depletion of DNMT1 without the
      high peak DAC levels that can cause DNA damage and cytotoxicity. THU also
      decreased interindividual variability in pharmacokinetics seen with DAC alone.
      One potential clinical application of DNMT1-targeted therapy is to increase fetal
      hemoglobin and treat hemoglobinopathy. Oral THU-DAC at a dose that would produce
      peak DAC concentrations of less than 0.2MUM administered 2*/wk for 8 weeks to
      nonhuman primates was not myelotoxic, hypomethylated DNA in the gamma-globin gene
      promoter, and produced large cumulative increases in fetal hemoglobin. Combining
      oral THU with oral DAC changes DAC pharmacology in a manner that may facilitate
      accessible noncytotoxic DNMT1-targeted therapy.

PMID- 22160382
TI  - Mechanisms and clinical significance of BIM phosphorylation in chronic
      lymphocytic leukemia.
AB  - B-cell receptor and microenvironment-derived signals promote accumulation of
      chronic lymphocytic leukemia (CLL) cells through increased proliferation and/or
      decreased apoptosis. In this study, we investigated the regulation of BIM, a
      proapoptotic BCL2-related protein, which is tightly regulated by phosphorylation.
      Surface IgM stimulation increased phosphorylation of 2 BIM isoforms, BIM(EL) and
      BIM(L), in a subset of CLL samples. In contrast, in normal B cells, anti-IgM
      triggered selective phosphorylation of BIM(EL) only. In CLL, anti-IgM-induced BIM
      phosphorylation correlated with unmutated IGHV gene status and with progressive
      disease. Strikingly, it was also associated with progressive disease within the
      mutated IGHV gene subset. BIM phosphorylation was dependent on MEK1/2 kinase
      activity, and we identified BIM(EL) serine 69, previously linked to pro-survival
      responses, as the major site of phosphorylation in CLL and in Ramos cells.
      BIM(EL)/BIM(L) phosphorylation was associated with release of the pro-survival
      protein MCL1. Coculture of CLL cells with HK cells, a model of the CLL
      microenvironment, promoted CLL cell survival and was associated with MEK1/2
      activation and BIM(EL) phosphorylation. Hence, BIM phosphorylation appears to
      play a key role in apoptosis regulation in CLL cells, potentially coordinating
      antigen and microenvironment-derived survival signals. Antigen-mediated effects
      on BIM may be an important determinant of clinical behavior.

PMID- 22160383
TI  - Administration of bortezomib before and after autologous stem cell
      transplantation improves outcome in multiple myeloma patients with deletion 17p.
AB  - In patients with multiple myeloma (MM), risk stratification by chromosomal
      abnormalities may enable a more rational selection of therapeutic approaches. In
      the present study, we analyzed the prognostic value of 12 chromosomal
      abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4
      trial. Because of the 2-arm design of the study, we were able to analyze the
      effect of a bortezomib-based treatment before and after autologous stem cell
      transplantation (arm B) compared with standard treatment without bortezomib (arm
      A). For allanalyzed chromosomal aberrations, progression-free survival (PFS) and
      overall survival (OS) were at least equal or superior in the bortezomib arm
      compared with the standard arm. Strikingly, patients with del(17p13) benefited
      the most from the bortezomib-containing treatment: the median PFS in arm A was
      12.0 months and in arm B it was 26.2 months (P = .024); the 3 year-OS for arm A
      was 17% and for arm B it was 69% (P = .028). After multivariate analysis,
      del(17p13) was an independent predictor for PFS (P < .0001) and OS (P < .0001) in
      arm A, whereas no statistically significant effect on PFS (P = .28) or OS (P =
      .12) was seen in arm B. In conclusion, the adverse impact of del(17p13) on PFS
      and OS could be significantly reduced by bortezomib-based treatment, suggesting
      that long-term administration of bortezomib should be recommended for patients
      carrying del(17p13).

PMID- 22160385
TI  - Remediation of hydrocarbons in crude oil-contaminated soils using Fenton's
      reagent.
AB  - Sandy soil samples spiked with Bonny light crude oil were subsequently treated
      with Fenton's reagent at acidic, neutral, and basic pH ranges. Oil extracts from
      these samples including an untreated one were analyzed 1 week later with a gas
      chromatograph to provide evidence of hydrocarbon depletion by the oxidant. The
      reduction of three broad hydrocarbon groups-total petroleum hydrocarbon (TPH);
      benzene, toluene, ethylbenzene, and xylene (BTEX); and polycyclic aromatic
      hydrocarbon (PAH) were investigated at various pHs. Hydrocarbon removal was
      efficient, with treatment at the acidic pH giving the highest removal of about
      96% for PAH, 99% for BTEX, and some TPH components experiencing complete
      disappearance. The four-ringed PAHs were depleted more than their three-ringed
      counterparts at the studied pH ranges.

PMID- 22160384
TI  - B-cell depletion and remissions of malignancy along with cytokine-associated
      toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T
      cells.
AB  - We conducted a clinical trial to assess adoptive transfer of T cells genetically
      modified to express an anti-CD19 chimeric Ag receptor (CAR). Our clinical
      protocol consisted of chemotherapy followed by an infusion of anti-CD19-CAR
      transduced T cells and a course of IL-2. Six of the 8 patients treated on our
      protocol obtained remissions of their advanced, progressive B-cell malignancies.
      Four of the 8 patients treated on the protocol had long-term depletion of normal
      polyclonal CD19(+) B-lineage cells. Cells containing the anti-CD19 CAR gene were
      detected in the blood of all patients. Four of the 8 treated patients had
      prominent elevations in serum levels of the inflammatory cytokines IFNgamma and
      TNF. The severity of acute toxicities experienced by the patients correlated with
      serum IFNgamma and TNF levels. The infused anti-CD19-CAR-transduced T cells were
      a possible source of these inflammatory cytokines because we demonstrated
      peripheral blood T cells that produced TNF and IFNgamma ex vivo in a CD19
      specific manner after anti-CD19-CAR-transduced T-cell infusions. Anti-CD19-CAR
      transduced T cells have great promise to improve the treatment of B-cell
      malignancies because of a potent ability to eradicate CD19(+) cells in vivo;
      however, reversible cytokine-associated toxicities occurred after CAR-transduced
      T-cell infusions.

PMID- 22160386
TI  - Baseline values for metals in soils on Fildes Peninsula, King George Island,
      Antarctica: the extent of anthropogenic pollution.
AB  - Metal contents (Al, Ca, Cd, Cr, Cu, Fe, Hg, Mg, Mn, Ni, Pb, Ti, and Zn) have been
      measured in 30 surface soils on Fildes Peninsula, King George Island, Antarctica,
      yielding values (in milligrams kilogram(-1)) of 41.57-80.65 (Zn), 2.76-60.52
      (Pb), 0.04-0.34 (Cd), 7.18-25.03 (Ni), 43,255-70,534 (Fe), 449-1,401 (Mn), 17.10
      64.90 (Cr), 1,440-25,684 (Mg), 10,941-49,354 (Ca), 51.10-176.50 (Cu), 4,388
      12,707 (Ti), 28,038-83,849 (Al), and for Hg (in nanograms gram(-1)) 0.01-0.06.
      Relative cumulative frequency analysis was used to determine the baseline values
      for the 13 metals. Compared with adjacent areas in Antarctica, Mg and Ni are
      significantly lower, but Cu is significantly higher than that of McMurdo Station.
      Enrichment factor analysis and the geo-accumulation index method were applied in
      order to determine the extent of anthropogenic contamination, and both show that
      Pb, Cd, and Hg have been significantly increased by human activities. Principal
      component analysis was used to identify the sources of metals in these soil
      samples.

PMID- 22160388
TI  - Structure and dynamics of nucleic acids.
AB  - In this chapter we describe the application of CW and pulsed EPR methods for the
      investigation of structural and dynamical properties of RNA and DNA molecules and
      their interaction with small molecules and proteins. Special emphasis will be
      given to recent applications of dipolar spectroscopy on nucleic acids.

PMID- 22160389
TI  - ABPP methodology: introduction and overview.
AB  - Activity-based protein profiling (ABPP) is emerging as a mature method for
      chemically interrogating the proteome of a cell. This chapter serves to introduce
      the reader to ABPP by providing overviews of the general principles of the
      technique, analytical methods used in ABPP, the classes of enzymes that can be
      specifically addressed by ABPP probes, and biological applications of ABPP.

PMID- 22160387
TI  - The physiology of the honey possum, Tarsipes rostratus, a small marsupial with a
      suite of highly specialised characters: a review.
AB  - Field and laboratory studies of the iconic nectarivorous and 'pollenivorous'
      honey possum, Tarsipes rostratus, are reviewed with the aim of identifying
      aspects of its physiology that are as yet poorly understood and needed to
      implement management strategies for its long-term conservation. Dietary
      specialisations include the loss of teeth, a modified gut with a high rate of
      passage, exceptionally low minimum nitrogen requirements, an apparently high
      basal metabolic rate and a permanently polyuric kidney. In contrast, its
      reproductive physiology is plesiomorphic, combining aspects such as a post-partum
      oestrus, embryonic diapause, photoperiodicity and extended maternal care that are
      usually separate characteristics of other marsupial groups. In common with a
      number of other marsupials, the honey possum has the potential for trichromatic
      colour vision and has been the subject of several studies attempting to correlate
      visual quality with ecological realities. Field physiological studies have
      established its high rates of nectar and pollen intake needed to maintain energy
      balance and highlight the need for a constant intake from floral sources. Early
      allometric studies suggesting that the honey possum's relatively low reproductive
      rate may be linked to a diet limited in protein have not been supported and
      nitrogen intakes in the field exceed by a factor of 10 the animal's basic
      requirements for balance. Measurements of rates of protein turnover in field
      caught lactating females suggest that they divert nitrogen from the protein pool
      to milk production by reducing rates of degradation, rather than by increasing
      rates of synthesis of protein. Although not yet an endangered species, the honey
      possum's habitat has been drastically reduced since European occupation of
      Australia and future-targeted research on the animal's unique physiology and
      habitat linkage is needed that can be translated into effective management
      practices. Only then will its long-term survival be assured.

PMID- 22160390
TI  - Supramolecular naphthalenediimide nanotubes.
AB  - Amino acid functionalized naphthalenediimides (NDIs) when dissolved in chloroform
      form a dynamic combinatorial library (DCL) in which the NDI building blocks are
      connected through reversible hydrogen bonds forming a versatile new
      supramolecular assembly in solution with intriguing host-guest properties. In
      chlorinated solvents the NDIs form supramolecular nanotubes which complex C(60),
      ion-pairs, and extended aromatic molecules. In the presence of C(70) a new
      hexameric receptor is formed at the expense of the nanotube; the equilibrium
      nanotube - hexameric receptor can be influenced by acid-base reactions. Achiral
      NDIs are incorporated in nanotubes formed by either dichiral or monochiral NDIs
      experiencing the "sergeants-and-soldiers" effect.

PMID- 22160391
TI  - Contemporary methods in structure determination of membrane proteins by solution
      NMR.
AB  - Integral membrane proteins are vital to life, being responsible for information
      and material exchange between a cell and its environment. Although high
      resolution structural information is needed to understand how these functions are
      achieved, membrane proteins remain an under-represented subset of the protein
      structure databank. Solution NMR is increasingly demonstrating its ability to
      help address this knowledge shortfall, with the development of a diverse array of
      techniques to counter the challenges presented by membrane proteins. Here we
      document the advances that are helping to define solution NMR as an effective
      tool for membrane protein structure determination. Developments introduced over
      the last decade in the production of isotope-labeled samples, reconstitution of
      these samples into the growing selection of NMR-compatible membrane-mimetic
      systems, and the approaches used for the acquisition and application of
      structural restraints from these complexes are reviewed.

PMID- 22160392
TI  - Benefits of recombinant adeno-associated virus (rAAV)-mediated insulinlike growth
      factor I (IGF-I) overexpression for the long-term reconstruction of human
      osteoarthritic cartilage by modulation of the IGF-I axis.
AB  - Administration of therapeutic genes to human osteoarthritic (OA) cartilage is a
      potential approach to generate effective, durable treatments against this slow,
      progressive disorder. Here, we tested the ability of recombinant adeno-associated
      virus (rAAV)-mediated overexpression of human insulinlike growth factor (hIGF)-I
      to reproduce an original surface in human OA cartilage in light of the
      pleiotropic activities of the factor. We examined the proliferative, survival and
      anabolic effects of the rAAV-hIGF-I treatment in primary human normal and OA
      chondrocytes in vitro and in explant cultures in situ compared with control
      (reporter) vector delivery. Efficient, prolonged IGF-I secretion via rAAV
      stimulated the biological activities of OA chondrocytes in all the systems
      evaluated over extended periods of time, especially in situ, where it allowed for
      the long-term reconstruction of OA cartilage (at least for 90 d). Remarkably,
      production of high, stable amounts of IGF-I in OA cartilage using rAAV
      advantageously modulated the expression of central effectors of the IGF-I axis by
      downregulating IGF-I inhibitors (IGF binding protein [IGFBP]-3 and IGFBP4) while
      up-regulating key potentiators (IGFBP5, the IGF-I receptor and downstream mitogen
      activated protein kinase/extracellular signal-regulated kinase 1/2 [MAPK/ERK-1/2]
      and phosphatidylinisitol-3/Akt [PI3K/Akt] signal transduction pathways), probably
      explaining the enhanced responsiveness of OA cartilage to IGF-I treatment. These
      findings show the benefits of directly providing an IGF-I sequence to articular
      cartilage via rAAV for the future treatment of human osteoarthritis.

PMID- 22160393
TI  - Homeobox D10 gene, a candidate tumor suppressor, is downregulated through
      promoter hypermethylation and associated with gastric carcinogenesis.
AB  - Homeobox D10 (HoxD10 ) gene plays a critical role in cell differentiation and
      morphogenesis during development. However, the function of HoxD10 in tumor
      progression remains largely unknown. We demonstrate that the expression of HoxD10
      is commonly downregulated in gastric cancer tissues (n = 33) and cell lines (n =
      8) relative to normal stomach tissues. Functionally, reexpression of HoxD10
      results in significant inhibition of cell survival, induction of cell apoptosis,
      and impairment of cell migration and invasion. Moreover, ectopic expression of
      HoxD10 suppresses gastric tumor growth in a mouse xenograft model. To identify
      target candidates of HoxD10, we performed cDNA microarray and showed that HoxD10
      regulates multiple downstream genes including IGFBP3. Reintroduction of HoxD10
      transcriptionally upregulates IGFBP3, activates caspase 3 and caspase 8, and
      subsequently induces cell apoptosis. Methylation specific PCR revealed that
      HoxD10 promoter DNA was hypermethylated in gastric cancer cell lines.
      Additionally, 5-aza demethylation treatment could transiently reactivate the
      expression of HoxD10 in gastric cancer cells. HoxD10 promoter methylation
      frequently was detected in gastric cancer tissues obtained from endoscopic
      biopsies (85.7%, 24/28) and surgically resected samples (82.6%, 57/69).
      Intestinal metaplasia tissues showed a 60% methylation rate (18/30), but no
      detectable methylation in normal stomach tissues (0%, 0/10). Taken together, our
      results suggest that HoxD10 functions as a candidate tumor suppressor in gastric
      cancer, which is inactivated through promoter hypermethylation.

PMID- 22160395
TI  - Elasticity changes anti-correlate with NO production for human endothelial cells
      stimulated with TNF-alpha.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a critical cytokine that is involved
      in systemic inflammatory response and contributes to the activation of the pro
      inflammatory phenotype of the endothelium. In the present study, effects of TNF
      alpha on morphology and elasticity of endothelium in relation to the production
      of NO and actin fiber reorganization were analyzed in human dermal microvascular
      endothelial cells. The cells were incubated in MCDB medium solution and
      stimulated with [Formula: see text] of TNF-alpha. Atomic force microscopy
      measurements have enabled characterization of cell morphology and elastic
      properties in physiological conditions. The spectrophotometric Griess method was
      applied to estimate nitric oxide (NO) production of the cells. We demonstrated
      that TNF-alpha-induced changes in elasticity of endothelium anti-correlate with
      NO production and are associated with the reorganization of actin cytoskeleton.

PMID- 22160394
TI  - Differential contribution of TM6 and TM12 to the pore of CFTR identified by three
      sulfonylurea-based blockers.
AB  - Previous studies suggested that four transmembrane domains 5, 6, 11, 12 make the
      greatest contribution to forming the pore of the CFTR chloride channel. We used
      excised, inside-out patches from oocytes expressing CFTR with alanine-scanning
      mutagenesis in amino acids in TM6 and TM12 to probe CFTR pore structure with four
      blockers: glibenclamide (Glyb), glipizide (Glip), tolbutamide (Tolb), and
      Meglitinide. Glyb and Glip blocked wildtype (WT)-CFTR in a voltage-, time-, and
      concentration-dependent manner. At V (M) = -120 mV with symmetrical 150 mM Cl(-)
      solution, fractional block of WT-CFTR by 50 MUM Glyb and 200 MUM Glip was 0.64 +/
      0.03 (n = 7) and 0.48 +/- 0.02 (n = 7), respectively. The major effects on block
      by Glyb and Glip were found with mutations at F337, S341, I344, M348, and V350 of
      TM6. Under similar conditions, fractional block of WT-CFTR by 300 MUM Tolb was
      0.40 +/- 0.04. Unlike Glyb, Glip, and Meglitinide, block by Tolb lacked time
      dependence (n = 7). We then tested the effects of alanine mutations in TM12 on
      block by Glyb and Glip; the major effects were found at N1138, T1142, V1147,
      N1148, S1149, S1150, I1151, and D1152. From these experiments, we infer that
      amino acids F337, S341, I344, M348, and V350 of TM6 face the pore when the
      channel is in the open state, while the amino acids of TM12 make less important
      contributions to pore function. These data also suggest that the region between
      F337 and S341 forms the narrow part of the CFTR pore.

PMID- 22160396
TI  - Preparation and purification of monoclonal antibodies against chloramphenicol.
AB  - Monoclonal antibodies (McAbs) against chloramphenicol (CAP) were produced to
      detect CAP residues, which could be toxic and possesses a potential threat to
      human health. The CAP-BSA conjugate was obtained by bovine serum albumin (BSA)
      coupled with CAP, and used to immunize the mice. The splenocytes from the
      immunized mice were fused with mouse myeloma cells SP2/0 to form hybridoma, which
      may secrete McAbs against CAP. Hybridomas 1D(1) and 3G(12) secreting McAbs
      against CAP were obtained by screening. Ascites containing McAbs were prepared by
      injecting 1 x 10(6) cells of hybridoma 1D(1) and 3G(12) into the abdomen of mice.
      Protein A affinity chromatography was used to purify McAbs against CAP in a
      single chromatographic step with recovery yield above 80% and purity above 95%
      and full recovery of antibody activity. Experiments showed that McAb 3G(12) was
      highly specific for CAP and had no cross-reactivity with analogues which have a
      structure similar to CAP. The IC(50) value was 50.8 ng/mL.

PMID- 22160399
TI  - C2 intralaminar (crossing/ipsilateral) fixation as a bailout procedure for failed
      transpedicular/pars interarticularis screw placement.

PMID- 22160398
TI  - Preventive effect of risedronate on bone loss and frailty fractures in elderly
      women treated with anastrozole for early breast cancer.
AB  - The aim of this study was to assess the effect of adjuvant anastrozole, alone or
      associated with risedronate, on BMD and bone fracture risk in women more than 70
      years old with hormone receptor-positive early breast cancer (EBC). In a group of
      51 elderly women (aged 76.4 +/- 5.0 years) considered for adjuvant aromatase
      inhibitors for EBC, 24 patients with T-scores >= -2 and no prevalent fractures
      received anastrozole 1 mg/day (group A), and 27 patients with T-scores < -2, or
      with T-scores >= -2 and prevalent fractures (group B), received anastrozole (1
      mg/day) plus risedronate (35 mg/week). Both groups received supplementation with
      1 g calcium carbonate and 800 IU vitamin D per day. Differences in BMD and
      frailty fractures were evaluated after 1 and 2 years. In group A, significant
      decreases in BMD were observed in the lumbar spine (Delta BMD, -0.030 +/- 0.04
      g/cm2, P < 0.05), femoral neck (Delta BMD, -0.029 +/- 0.05 g/cm2, P < 0.05), and
      trochanter (Delta BMD, -0.026 +/- 0.03 g/cm2, P < 0.01) after 2 years. The
      greatest percent reduction in height (Hpr) emerged in the thoracic spine (3.6 +/-
      2.4%, P < 0.01), although only one incident vertebral fracture was observed. In
      group B, BMD increased in the lumbar spine (Delta BMD, 0.038 +/- 0.04, P <
      0.001), although no significant changes were seen in the hip regions. The decline
      in Hpr was negligible (about 1%). No incident fractures were observed at follow
      up. In conclusion, anastrozole treatment for EBC in elderly women seems to have
      only mild negative effects on the femoral bone. Risedronate makes the use of
      anastrozole safer, even for osteopenic or osteoporotic elderly patients.

PMID- 22160397
TI  - Can vitamin D slow down the progression of chronic kidney disease?
AB  - Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) is
      the cornerstone of renoprotective therapy, and the reduction of persistent RAAS
      activation is considered to be an important target in the treatment of chronic
      kidney disease (CKD). Vitamin D is a steroid hormone that controls a broad range
      of metabolic and cell regulatory functions. It acts as a transcription factor and
      can suppress the renin gene, thereby acting as a negative endocrine regulator of
      RAAS. RAAS activation can reduce renal Klotho expression, and the Klotho
      fibroblast growth factor 23 interaction may further reduce the production of
      active vitamin D. Results from both clinical and experimental studies suggest
      that vitamin D therapy is associated with a reduction in blood pressure and left
      ventricular hypertrophy and improves cardiovascular outcomes. In addition, a
      reduction in angiotensin II through RAAS blockade may have anti-proteinuric and
      anti-fibrotic effects. Vitamin D has also been shown to modulate the immune
      system, regulate inflammatory responses, improve insulin sensitivity and reduce
      high-density lipoprotein cholesterol. Taken together, these pleiotropic effects
      of vitamin D may slow down the progression of CKD. In this review, we discuss the
      experimental and early clinical findings that suggest a renoprotective effect of
      vitamin D, thereby providing an additional rationale beyond mineral metabolism
      for the close monitoring of, and supplementation with vitamin D from the earliest
      stages of CKD.

PMID- 22160400
TI  - Outcomes of surgical treatment for hemifacial spasm associated with the vertebral
      artery: severity of compression, indentation, and color change.
AB  - OBJECT: The object of surgical treatment for hemifacial spasm (HFS) is the
      exclusion of pulsatile neurovascular compression of the root exit zone (REZ).
      However, spasm persists transiently or permanently in some cases even after
      complete decompression. In particular, we mainly experience these results when
      the vertebral artery (VA) is the offender. Hence, we verified color changes of
      the nerve and indentations from within the operative field in HFS patients with
      the VA as the offender. So, we reviewed retrospectively the records of those
      patients who were treated with microvascular decompression (MVD) in order to
      assess the relationship between operative findings and clinical results. METHODS:
      A total of 232 patients with HFS associated with the VA were treated with MVD
      between January 1994 and January 2009 at our institution. The patients were
      classified into one of the following three categories based on compression
      severity: Group I, mild; Group II, moderate; Group III, severe. The patients were
      also classified into one of the following four categories based on the existence
      of indentation and discoloration of nerve VII: Group A (-/-), B (+/-), C (-/+),
      or D (+/+). RESULTS: A total of 94.2% and 96.6% of the patients in Groups I and
      II, respectively, had improved to grades I-II at the last follow-up. The surgical
      outcomes of Group III were slightly poorer than those of Groups I and II. Group A
      showed the poorest outcomes with 60% of the patients classified as grades III-IV.
      In Group B, 98.4% of the patients showed a marked improvement and Groups C and D
      showed relatively poor outcomes compared with those of Group B. CONCLUSIONS:
      Severe deviations and color changes of the facial nerves may be the risk factors
      for poor surgical outcomes. Future studies with larger sample sizes and
      investigations of the pathophysiology underlying these findings are needed.

PMID- 22160402
TI  - Biological and clinical heterogeneity of MYCN-amplified medulloblastoma.
AB  - Focal high-level amplifications of MYC (or MYCC) define a subset of high-risk
      medulloblastoma patients. However, the prognostic role of MYCN oncogene
      amplification remains unresolved. We aimed to evaluate the prognostic value of
      this alteration alone and in combination with biological modifiers in 67
      pediatric medulloblastomas with MYCN amplification (MYCN-MB). Twenty-one MYCN-MB
      were examined using gene expression profiling and array-CGH, whereas for 46
      tumors immunohistochemical analysis and FISH were performed. All 67 tumors were
      further subjected to mutational analyses. We compared molecular, clinical, and
      prognostic characteristics both within biological MYCN-MB groups and with non
      amplified tumors. Transcriptomic analysis revealed SHH-driven tumorigenesis in a
      subset of MYCN-MBs indicating a biological dichotomy of MYCN-MB. Activation of
      SHH was accompanied by variant-specific cytogenetic aberrations including
      deletion of 9q in SHH tumors. Non-SHH MB were associated with gain of 7q and
      isochromosome 17q/17q gain. Among clinically relevant variables, SHH subtype and
      10q loss for non-SHH tumors comprised the most powerful markers of favorable
      prognosis in MYCN-MB. In conclusion, we demonstrate considerable heterogeneity
      within MYCN-MB in terms of genetics, tumor biology, and clinical outcome. Thus,
      assessment of disease group and 10q copy-number status may improve risk
      stratification of this group and may delineate MYCN-MB with the same dismal
      prognosis as MYC amplified tumors. Furthermore, based on the enrichment of MYCN
      and GLI2 amplifications in SHH-driven medulloblastoma, amplification of these
      downstream signaling intermediates should be taken into account before a patient
      is enrolled into a clinical trial using a smoothened inhibitor.

PMID- 22160401
TI  - The major facilitator superfamily-type protein LbtC promotes the utilization of
      the legiobactin siderophore by Legionella pneumophila.
AB  - The Gram-negative bacterium Legionella pneumophila elaborates the siderophore
      legiobactin. We previously showed that cytoplasmic LbtA helps mediate legiobactin
      synthesis, inner-membrane LbtB promotes export of legiobactin, and outer-membrane
      LbtU acts as the ferrisiderophore receptor. RT-PCR analyses now identified lbtC
      as an iron-repressed gene that is the final gene in an operon containing lbtA and
      lbtB. In silico analysis predicted that LbtC is an inner-membrane protein that
      belongs to the major facilitator superfamily (MFS). Although capable of normal
      growth in standard media, lbtC mutants were defective for growth on iron-depleted
      agar media. While producing normal levels of legiobactin, lbtC mutants were
      unable to utilize supplied legiobactin to stimulate growth on iron-depleted media
      and displayed an impaired ability to take up radiolabelled iron. All lbtC mutant
      phenotypes were complemented by reintroduction of an intact copy of lbtC. When a
      cloned copy of both lbtC and lbtU was introduced into a heterologous bacterium
      (Legionella longbeachae), the organism acquired the ability to utilize
      legiobactin to grow better on low-iron media. Together, these data indicate that
      LbtC is involved in the uptake of legiobactin, and based upon its predicted
      location is most likely the mediator of ferrilegiobactin transport across the
      inner membrane. The data are also a unique documentation of how an MFS protein
      can promote bacterial iron-siderophore import, standing in contrast to the vast
      majority of studies which have defined ABC-type permeases as the mediators of
      siderophore import across the Gram-negative inner membrane or the Gram-positive
      cytoplasmic membrane.

PMID- 22160403
TI  - Genetic counseling through hope.

PMID- 22160404
TI  - Exercise-induced right ventricular dysfunction and structural remodelling in
      endurance athletes.
AB  - AIMS: Endurance training may be associated with arrhythmogenic cardiac
      remodelling of the right ventricle (RV). We examined whether myocardial
      dysfunction following intense endurance exercise affects the RV more than the
      left ventricle (LV) and whether cumulative exposure to endurance competition
      influences cardiac remodelling (including fibrosis) in well-trained athletes.
      METHODS AND RESULTS: Forty athletes were studied at baseline, immediately
      following an endurance race (3-11 h duration) and 1-week post-race. Evaluation
      included cardiac troponin (cTnI), B-type natriuretic peptide, and
      echocardiography [including three-dimensional volumes, ejection fraction (EF),
      and systolic strain rate]. Delayed gadolinium enhancement (DGE) on cardiac
      magnetic resonance imaging (CMR) was assessed as a marker of myocardial fibrosis.
      Relative to baseline, RV volumes increased and all functional measures decreased
      post-race, whereas LV volumes reduced and function was preserved. B-type
      natriuretic peptide (13.1 +/- 14.0 vs. 25.4 +/- 21.4 ng/L, P = 0.003) and cTnI
      (0.01 +/- .03 vs. 0.14 +/- .17 MUg/L, P < 0.0001) increased post-race and
      correlated with reductions in RVEF (r = 0.52, P = 0.001 and r = 0.49, P = 0.002,
      respectively), but not LVEF. Right ventricular ejection fraction decreased with
      increasing race duration (r = -0.501, P < 0.0001) and VO(2)max (r = -0.359, P =
      0.011). Right ventricular function mostly recovered by 1 week. On CMR, DGE
      localized to the interventricular septum was identified in 5 of 39 athletes who
      had greater cumulative exercise exposure and lower RVEF (47.1 +/- 5.9 vs. 51.1 +/
      3.7%, P = 0.042) than those with normal CMR. CONCLUSION: Intense endurance
      exercise causes acute dysfunction of the RV, but not the LV. Although short-term
      recovery appears complete, chronic structural changes and reduced RV function are
      evident in some of the most practiced athletes, the long-term clinical
      significance of which warrants further study.

PMID- 22160405
TI  - Exercise-induced arrhythmogenic right ventricular cardiomyopathy: fact or
      fallacy?

PMID- 22160406
TI  - Use of microperimetry to compare macular light sensitivity in eyes with open
      angle and angle-closure glaucoma.
AB  - PURPOSE: Use of microperimetry to compare macular light sensitivity in early and
      moderate primary open-angle glaucoma (POAG), chronic angle-closure glaucoma
      (CACG), and normal controls. PATIENTS AND METHODS: A cross-sectional, case
      control, comparative study. A total of 126 eyes from 126 subjects, 53 normal
      eyes, 50 POAG eyes, and 23 CACG eyes were studied. A macular 10 degrees  program
      was performed with MP-1 microperimetry. The mean sensitivities (MS) of the
      central 2 degrees , 6 degrees , and 10 degrees  visual fields were compared among
      the POAG, CACG, and normal controls. The mean light sensitivities of the four
      quadrants in the central 6 degrees  were also analyzed in each group. RESULTS:
      The MS of the central 2 degrees , 6 degrees , 10 degrees , and total macular
      areas in the POAG patients were significantly reduced compared with those for the
      normal controls (all P < 0.05). The MS of the central 6 degrees , 10 degrees ,
      and total areas, except those at the central 2 degrees , in the CACG patients
      were significantly reduced. In the central 6 degrees , more severe loss of MS was
      observed in the inferotemporal quadrant in the POAG group. In the CACG group, the
      reduction in the MS among the four quadrants was not significantly different (P =
      0.623). CONCLUSIONS: Different patterns of macular function damage were
      identified in both early and moderate stage POAG and in CACG patients.

PMID- 22160407
TI  - Video-assisted thoracoscopic patent ductus arteriosus closure in 2,000 patients.
AB  - Video-assisted thoracoscopic surgery has proved to be a safe and effective method
      with low complication and high success rates. From 1997 to 2008, 2,000
      consecutive patients with patent ductus arteriosus underwent closure of the
      ductus with 2 titanium clips via a video-assisted thoracoscopic technique.
      Complete closure was confirmed using our handmade intraesophageal stethoscope.
      The mean age was 5.2 years, and mean weight was 9.8 kg. One death was reported 1
      month after surgery, due to sepsis during hospitalization for chylothorax
      treatment. The procedure was converted to an emergency thoracotomy in one case,
      due to ductal wall rupture. There were 4 late residual shunts treated via
      thoracotomy. We observed transient laryngeal nerve dysfunction in 14 patients.
      All patients were reassessed by postoperative echocardiography. The mean
      procedure (skin-to-skin) time was 10 +/- 2 min, and hospitalization was 21 h.
      This study indicates that video-assisted thoracoscopic closure of patent ductus
      arteriosus is a safe, simple, and cost-effective method with low complication and
      high success rates. Furthermore, the cosmetic benefits make it appropriate as an
      out-patient procedure.

PMID- 22160408
TI  - NT-pro-brain natriuretic peptide levels after valve replacement.
AB  - Elevated plasma N-terminal pro-brain natriuretic peptide levels have been
      demonstrated in patients with chronic valvular disease. To assess whether changes
      in N-terminal pro-brain natriuretic peptide levels after mitral, aortic, and
      double-valve replacement reflect changes in heart failure symptoms, a prospective
      observational nonrandomized study was undertaken in 24 consecutive patients (mean
      age, 55.3 +/- 16.2 years; 58% male) undergoing mitral and/or aortic valve
      replacement. Mitral valve replacement was carried out in 12 patients, aortic
      valve replacement in 8, and combined mitral and aortic valve replacement in 4. N
      terminal pro-brain natriuretic peptide measurements, echocardiography, and
      functional class assessment were performed before and 6 months after surgery. A
      decrease in N-terminal pro-brain natriuretic peptide at 6 months postoperatively
      was significantly associated with decreased left atrial dimension, left
      ventricular end-diastolic and end-systolic dimensions, increased ejection
      fraction, and improvement in functional class. Thus we can hypothesize that
      measurement of N-terminal pro-brain natriuretic peptide might allow early
      detection of any clinical deterioration as well as assessment of the long-term
      outcome in valve replacement patients.

PMID- 22160409
TI  - Totally endoscopic atrial septal repair using no robotic techniques.
AB  - Standard surgical closure of an atrial septal defect via sternotomy is safe and
      effective. To avoid sternotomy and improve the cosmetic result, minimally
      invasive cardiac surgery has emerged as an alternative. Robot-assisted totally
      endoscopic atrial septal defect repair is convincingly superior, but the robotic
      system is expensive and complicated. We describe a technique of totally
      endoscopic closed-chest atrial septal defect closure without the aid of a robotic
      device. Twenty patients underwent totally endoscopic atrial septal defect repair
      using no robotic techniques between May 2009 and December 2009. No major
      intraoperative or postoperative complications were observed. One operation was
      converted to a conventional sternotomy because bleeding from the aortic root
      could not be controlled. Closure of an atrial septal defect can be performed
      safely and effectively via an endoscopic approach using no robotic techniques.

PMID- 22160410
TI  - Coronary pseudoaneurysm in a non-polymer drug-eluting stent: a rare entity.
AB  - Coronary pseudoaneurysms following implantation of drug-eluting stents, although
      rare, are not unknown. Nearly all such cases have been reported in patients with
      sirolimus or paclitaxel polymer-based stents. We describe a case of coronary
      pseudoaneurysm developing with a non-polymer-based drug-eluting stent in a 50
      year-old man who was successfully managed by coronary artery bypass grafting.

PMID- 22160411
TI  - An interrupted technique for difficult distal anastomosis during arch surgery.
AB  - During aortic arch replacement, construction of the distal anastomosis represents
      the crucial step because of the time limit of circulatory arrest. If the
      aneurysmal neck is located at the level of the 5(th) thoracic vertebra, it
      becomes difficult to carry out through a sternotomy approach. We describe a case
      in which an interrupted suture technique, similar to that used for valve
      replacement, was employed to maximize the limited exposure and achieve a water
      tight anastomosis.

PMID- 22160412
TI  - Coagulase-negative Staphylococcus endocarditis: Staphylococcus lugdunensis.
AB  - Staphylococcus lugdunensis is an infrequent cause of native valve endocarditis. A
      case of triple-valve involvement of Staphylococcus lugdunensis with intracardiac
      fistula formation in a 47-year-old woman was managed successfully with surgery.
      The importance of early diagnosis and prompt referral for surgical treatment is
      highlighted.

PMID- 22160413
TI  - Ruptured saphenous vein graft aneurysm after aortocoronary bypass grafting.
AB  - Computed tomography demonstrated a giant saphenous vein graft aneurysm that
      compressed the right atrium of a 72-year-old woman 20 years after undergoing
      coronary artery bypass grafting. Angiography revealed contrast medium leakage in
      the mid-portion of the graft aneurysm. Aneurysmectomy was performed without
      repeat grafting. Postoperative myocardial scintigraphy demonstrated no
      significant myocardial ischemia. The ischemic effect of non-revascularization
      should be considered preoperatively because of the difficulties with repeat
      grafting.

PMID- 22160414
TI  - A case of aortoesophageal fistula.
AB  - Aneurysms of the thoracic aorta can have various manifestations, some of which
      may simulate esophageal diseases, clinically and radiographically.
      Aortoesophageal fistula is rare and usually fatal. We report a case of
      aortoesophageal fistula presenting with progressive dysphagia and intermittent
      episodes of upper gastrointestinal bleeding.

PMID- 22160415
TI  - Aneurysm of sinus of Valsalva: uncommon presentation.
AB  - A 28-year-old man presented with acute onset of chest pain. Transthoracic
      echocardiography confirmed an aneurysm of the sinus of Valsalva dissecting into
      the interventricular septum. During the next 12 h, the aneurysm enlarged to
      involve the entire interventricular septum, and the patient developed features of
      cardiac tamponade. He underwent successful surgical repair.

PMID- 22160416
TI  - Thoracoscopic management of spontaneous pneumothorax due to azygos lobe bullae.
AB  - A 22-year-old man presented with recurrent right-sided spontaneous pneumothorax
      caused by rupture of azygos lobe bullae. Surgical management was successfully
      completed using a video-assisted thoracoscopic approach. Resection of the bullae
      harboring azygos lobe and subsequent pleurodesis were performed, sparing the meso
      azygos and azygos vein.

PMID- 22160417
TI  - Fenestration closure in a calcified ventricular septal defect patch.
AB  - Ventricular septal defect closure with a fenestrated patch is a recognized rescue
      maneuver to decrease the risk of right ventricular failure after complete repair
      in patients with pulmonary atresia. If the fenestration needs surgical closure,
      severe calcification of the patch may make it extremely difficult. We describe
      the closure of such a defect in a 6-year-old boy, using a double Dacron patch
      sandwich.

PMID- 22160418
TI  - Adenocarcinoma in pulmonary sequestration.
AB  - A 67-year-old male smoker presented with hemoptysis and recurrent pneumonia.
      Chest computed tomography showed an emphysematous cyst and air-fluid level
      cavities in the left lower lobe. A left lower lobectomy was performed. The
      intraoperative finding was intralobar sequestration. Histopathology revealed
      adenocarcinoma within the sequestrated lobe. Only 8 cases of lung cancer and
      sequestration have been reported since 1963.

PMID- 22160419
TI  - Ruptured pulmonary artery aneurysm: a surgical emergency.
AB  - Idiopathic pulmonary artery aneurysm rupture was diagnosed in a 79-year-old man
      who presented with a dry cough. He was considered unlikely to tolerate extensive
      pulmonary artery reconstruction or lung resection; hence, he was salvaged by
      timely ligation of the distal pulmonary artery at the origin of the aneurysm.

PMID- 22160420
TI  - Simple home-made suction device to aid excision of friable atrial myxoma.
AB  - Atrial myxoma, especially the papillary subtype, is known to be friable and
      gelatinous. Manipulation of an atrial myxoma during surgery can be very
      difficult, and not uncommonly results in fragmentation and embolization of part
      of the tumor. The conventional method using a metallic spoon to manipulate the
      tumor is widely practiced because alternatives are sparse. We describe a novel
      home-made suction device to aid the excision of friable atrial myxomas.

PMID- 22160421
TI  - Angina in an adolescent.

PMID- 22160422
TI  - Stridor with recurrent chest infection.

PMID- 22160423
TI  - Pneumopericardium from esophageal-pericardial fistula due to cancer recurrence.

PMID- 22160424
TI  - Missing floating thrombus in the aorta.

PMID- 22160425
TI  - Identification of a Delta5-like fatty acyl desaturase from the cephalopod Octopus
      vulgaris (Cuvier 1797) involved in the biosynthesis of essential fatty acids.
AB  - Long-chain polyunsaturated fatty acids (LC-PUFA) have been identified as
      essential compounds for common octopus (Octopus vulgaris), but precise dietary
      requirements have not been determined due, in part, to the inherent difficulties
      of performing feeding trials on paralarvae. Our objective is to establish the
      essential fatty acid (EFA) requirements for paralarval stages of the common
      octopus through characterisation of the enzymes of endogenous LC-PUFA
      biosynthetic pathways. In this study, we isolated a cDNA with high homology to
      fatty acyl desaturases (Fad). Functional characterisation in recombinant yeast
      showed that the octopus Fad exhibited Delta5-desaturation activity towards
      saturated and polyunsaturated fatty acyl substrates. Thus, it efficiently
      converted the yeast's endogenous 16:0 and 18:0 to 16:1n-11 and 18:1n-13,
      respectively, and desaturated exogenously added PUFA substrates 20:4n-3 and 20:3n
      6 to 20:5n-3 (EPA) and 20:4n-6 (ARA), respectively. Although the Delta5 Fad
      enables common octopus to produce EPA and ARA, the low availability of its
      adequate substrates 20:4n-3 and 20:3n-6, either in the diet or by limited
      endogenous synthesis from C(18) PUFA, might indicate that EPA and ARA are indeed
      EFA for this species. Interestingly, the octopus Delta5 Fad can also participate
      in the biosynthesis of non-methylene-interrupted FA, PUFA that are generally
      uncommon in vertebrates but have been found previously in marine invertebrates,
      including molluscs, and now also confirmed to be present in specific tissues of
      common octopus.

PMID- 22160426
TI  - Altered patterns of multiple recombinant events are associated with
      nondisjunction of chromosome 21.
AB  - We have previously examined characteristics of maternal chromosomes 21 that
      exhibited a single recombination on 21q and proposed that certain recombination
      configurations are risk factors for either meiosis I (MI) or meiosis II (MII)
      nondisjunction. The primary goal of this analysis was to examine characteristics
      of maternal chromosomes 21 that exhibited multiple recombinant events on 21q to
      determine whether additional risk factors or mechanisms are suggested. In order
      to identify the origin (maternal or paternal) and stage (MI or MII) of the
      meiotic errors, as well as placement of recombination, we genotyped over 1,500
      SNPs on 21q. Our analyses included 785 maternal MI errors, 87 of which exhibited
      two recombinations on 21q, and 283 maternal MII errors, 81 of which exhibited two
      recombinations on 21q. Among MI cases, the average location of the distal
      recombination was proximal to that of normally segregating chromosomes 21 (35.28
      vs. 38.86 Mb), a different pattern than that seen for single events and one that
      suggests an association with genomic features. For MII errors, the most proximal
      recombination was closer to the centromere than that on normally segregating
      chromosomes 21 and this proximity was associated with increasing maternal age.
      This pattern is same as that seen among MII errors that exhibit only one
      recombination. These findings are important as they help us better understand
      mechanisms that may underlie both age-related and nonage-related meiotic
      chromosome mal-segregation.

PMID- 22160427
TI  - Molecular capsules derived from resorcin[4]arenes by metal-coordination.
AB  - A short introduction to the fundamental features and recent developments of
      supramolecular chemistry is presented besides defining scope and limitation of
      this review article. A brief overview about calix[n]arenes and especially
      resorcin[4]arenes and their conformationally rigid cavitands is given. Selected
      examples are presented to demonstrate the dependence of self-assembly of
      cavitands exhibiting different flexibility either due to their basic macrocycle
      or due to flexible receptor units commonly located at the o,o'-position of the
      resorcinarene ring. In addition, the process of self-assembly is also controlled
      by metal coordination geometry as shown by one example. The receptor units may
      also be connected at the methylene group of the cavitand as shown by one example.
      Examples of supramolecular architectures are presented utilizing the special
      features of 2,2':6',2"-terpyridine (terpy) metal-binding ligand. The synthesis
      and characterization of a metallo-supramolecular Zn-coordination cage with a
      diameter of 4-5 nm based on a cavitand-terpy building block is presented in
      detail.

PMID- 22160428
TI  - Impaired gremlin 1 (GREM1) expression in cumulus cells in young women with
      diminished ovarian reserve (DOR).
AB  - PURPOSE: A symbiotic relationship between ovarian granulosa cells (GC) and the
      developing oocyte is critical. Genetic modulations in GC's can lead to
      reproductive insufficiency, highlighting the role of GC's in reproductive
      competence. Utilizing gene expression analyses in cumulus GC's, we attempt to
      enhance our understanding of mechanisms that may contribute to poor reproductive
      capacity in young women with diminished ovarian reserve (DOR). METHODS: We
      measured gremlin 1 (GREM1) gene expression in GC's from infertile women <38 years
      undergoing in vitro fertilization in the context of DOR. RESULTS: GREM1, a member
      of the differential screening-selected gene aberrative in neuroblastoma (DAN)
      family of genes known for its highly regulated expression pattern during
      folliculogenesis and a downstream effecter of oocyte-derived growth and
      differentiation factor 9, was down-regulated 3-fold (-3.08) in women with DOR
      versus control; down-regulation was confirmed by qRT-PCR (-4.02). CONCLUSION:
      This is the first demonstration linking differential expression of Gremlin with
      etiology of infertility in women.

PMID- 22160429
TI  - Short-term in-vitro culture of goat enriched spermatogonial stem cells using
      different serum concentrations.
AB  - PURPOSE: To investigate the effect of serum supplementing on short-term culture,
      fate determination and gene expression of goat spermatogonial stem cells (SSCs).
      METHODS: Crude testicular cells were plated over Datura-Stramonium Agglutinin
      (DSA) for 1 h, and non-adhering cells were cultured in the presence of different
      serum concentrations (1, 5, 10, and 15%) for 7 days in a highly enriched medium
      initially developed in mice. Colonies developed in each group were used for the
      assessment of morphology, immunocytochemistry, and gene expression. RESULTS:
      Brief incubation of testicular cells with DSA resulted in a significant increase
      in the number of cells that expressed the germ cell marker (VASA). The expression
      of THY1, a specific marker of undifferentiated spermatogonia, was significantly
      higher in colonies developed in the presence of 1% rather than 5, 10 and 15%
      serum. CONCLUSION: Goat SSCs could proliferate and maintain in SSC culture media
      for 1 week at serum concentrations as low as 1%, while higher concentrations had
      detrimental effects on SSC culture/expansion.

PMID- 22160430
TI  - Towards an understanding of wheat chloroplasts: a methodical investigation of
      thylakoid proteome.
AB  - We utilized Percoll density gradient centrifugation to isolate and fractionate
      chloroplasts of Korean winter wheat cultivar cv. Kumgang (Triticum aestivum L.).
      The resulting protein fractions were separated by one dimensional polyacrylamide
      gel electrophoresis (1D-PAGE) coupled with LTQ-FTICR mass spectrometry. This
      enabled us to detect and identify 767 unique proteins. Our findings represent the
      most comprehensive exploration of a proteome to date. Based on annotation
      information from the UniProtKB/Swiss-Prot database and our analyses via WoLF
      PSORT and PSORT, these proteins are localized in the chloroplast (607 proteins),
      chloroplast stroma (145), thylakoid membrane (342), lumens (163), and integral
      membranes (166). In all, 67% were confirmed as chloroplast thylakoid proteins.
      Although nearly complete protein coverage (89% proteins) has been accomplished
      for the key chloroplast pathways in wheat, such as for photosynthesis, many other
      proteins are involved in regulating carbon metabolism. The identified proteins
      were assigned to 103 functional categories according to a classification system
      developed by the iProClass database and provided through Protein Information
      Resources. Those functions include electron transport, energy, cellular
      organization and biogenesis, transport, stress responses, and other metabolic
      processes. Whereas most of these proteins are associated with known complexes and
      metabolic pathways, about 13% of the proteins have unknown functions. The
      chloroplast proteome contains many proteins that are localized to the thylakoids
      but as yet have no known function. We propose that some of these familiar
      proteins participate in the photosynthetic pathway. Thus, our new and
      comprehensive protein profile may provide clues for better understanding that
      photosynthetic process in wheat.

PMID- 22160431
TI  - Systematic analysis of genomic organization and heterogeneities of miRNA cluster
      in vertebrates.
AB  - The clustering propensity of microRNA genes is a common biological phenomenon in
      various animal and plant species. To gain novel insight into genomic organization
      and potential functional heterogeneities of miRNA clusters in vertebrates from a
      genome scale, we used large scale data and presented a comprehensive analysis to
      examine various features of genomic organization of miRNA clusters across seven
      vertebrates by a combination of comparative genomics and bioinformatics
      approaches. The results of pair-wise distance analysis of same-strand consecutive
      miRNAs suggested that the fractions of the miRNA gene pairs are higher at
      relatively short pair-wise distances than those of protein-coding genes and other
      non-coding RNA genes. Especially relatively small number of miRNAs is more
      clustered at very short pair-wise distances than expected at random. We further
      observed significant difference between real miRNA clusters and randomly
      organized clusters for different aspects, including higher overlap of target
      genes, fewer seed types and significant enrichment in diseases. However, the
      extent of these features of clustered miRNAs has a different tendency and largely
      depends on inter-miRNA distances because of diverse clustering propensity of
      miRNAs in vertebrates, suggesting that this cooperated function or cooperative
      effects between miRNAs in clusters perhaps be affected by inter-miRNA distances.

PMID- 22160432
TI  - Effects of dual tasking on the postural performance of people with and without
      multiple sclerosis: a pilot study.
AB  - People with multiple sclerosis (MS) exhibit both cognitive and postural
      impairments. This study examined the effects of MS and of dual tasking on
      postural performance, and explored associations among dual-task postural
      performance, cognitive capacity, fear of falling, and fatigue. Thirteen subjects
      with MS (Expanded Disability Status Scale: 0-4.5) and 13 matched subjects without
      MS performed three tasks of standing postural control, with and without dual
      tasking amid an auditory Stroop task: (1) step initiation, (2) forward leaning to
      the limits of stability, and (3) postural responses to rotations of the support
      surface. Two-factor general linear models were used to evaluate differences
      between the groups (with or without MS) and two conditions (single or dual
      tasking) for each postural task. During step initiation, dual tasking
      significantly delayed the onset of the anticipatory postural adjustment (APA)
      more for the subjects with MS than for those without MS, and step lengths
      increased for the subjects with MS but decreased for those without MS. No other
      significant group-by-condition interactions were evident on the recorded
      variables of stepping, leaning, postural responses, or Stroop-response accuracies
      and latencies. The scores for the subjects with MS on the Modified Fatigue Impact
      Scale significantly associated with the change between single-task to dual-task
      conditions in APA onset and foot-lift onset during step initiation as well as in
      lean position variability and lean onset times during forward leaning. The
      results suggest dual-task effects were more evident during step initiation and
      are associated with levels of fatigue for subjects with MS.

PMID- 22160433
TI  - Drummer's lower limb dystonia.

PMID- 22160435
TI  - Classification of air quality using fuzzy synthetic multiplication.
AB  - Proper identification of environment's air quality based on limited observations
      is an essential task to meet the goals of environmental management. Various
      classification methods have been used to estimate the change of air quality
      status and health. However, discrepancies frequently arise from the lack of clear
      distinction between each air quality, the uncertainty in the quality criteria
      employed and the vagueness or fuzziness embedded in the decision-making output
      values. Owing to inherent imprecision, difficulties always exist in some
      conventional methodologies when describing integrated air quality conditions with
      respect to various pollutants. Therefore, this paper presents two fuzzy
      multiplication synthetic techniques to establish classification of air quality.
      The fuzzy multiplication technique empowers the max-min operations in "or" and
      "and" in executing the fuzzy arithmetic operations. Based on a set of air
      pollutants data carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, and
      particulate matter (PM(10)) collected from a network of 51 stations in Klang
      Valley, East Malaysia, Sabah, and Sarawak were utilized in this evaluation. The
      two fuzzy multiplication techniques consistently classified Malaysia's air
      quality as "good." The findings indicated that the techniques may have
      successfully harmonized inherent discrepancies and interpret complex conditions.
      It was demonstrated that fuzzy synthetic multiplication techniques are quite
      appropriate techniques for air quality management.

PMID- 22160434
TI  - The association of systemic lupus erythematosus and myasthenia gravis: a series
      of 17 cases, with a special focus on hydroxychloroquine use and a review of the
      literature.
AB  - The coexistence of systemic lupus erythematosus (SLE) and myasthenia gravis (MG)
      is rarely reported, and most of the published studies are case reports.
      Hydroxychloroquine, an antimalarial agent, is an essential treatment in patients
      with SLE but special caution is recommended when used in MG patients. We
      retrospectively analyzed the clinical features, laboratory findings, and outcome
      of 17 patients with both diseases with a special focus regarding
      hydroxychloroquine use and with a review of the literature. All patients were
      women. The mean age at MG onset and SLE diagnosis was 34.5 [14-64] and 37.8 [18
      72] years, respectively. The presenting symptoms of MG were limb weakness (94%),
      ocular (88%) and bulbar involvement (53%). Autoantibodies against the
      acetylcholine receptor were positive in 94% of cases. The main manifestations of
      SLE included arthritis (88%), cytopenias (53%) and skin rash (41%). Treatment of
      SLE required hydroxychloroquine (94%), steroids (47%) and immunosuppressive drugs
      (18%). Among eight patients (47%) who developed MG after initiation of
      hydroxychloroquine, the question of induction of MG by hydroxychloroquine was
      raised in one patient. On the other hand, an exacerbation of myasthenic symptoms
      was only seen in one of the eight patients who received hydroxychloroquine after
      the diagnosis of MG. Including our cases, we reviewed a total of 70 patients with
      SLE and MG. Compared with a large series of 1,000 unselected SLE patients, those
      with associated MG were older, had lower incidence of cutaneous, renal, and
      neurological manifestations, and higher frequency of anticardiolipin antibodies
      and lupus anticoagulant. In conclusion, the clinical pattern of patients with SLE
      and MG seems to be characterized by a less severe course of SLE and higher
      frequency of antiphospholipid antibodies. Hydroxychloroquine treatment appears to
      be safe in this setting.

PMID- 22160436
TI  - Decreased body weight in young Osterix-Cre transgenic mice results in delayed
      cortical bone expansion and accrual.
AB  - Conditional gene inactivation using the Cre/loxP system has lead to significant
      advances in our understanding of the function of genes in a wide range of
      disciplines. It is becoming increasingly apparent in the literature, that Cre
      transgenic mice may themselves have a phenotype. In the following study we
      describe the bone phenotype of a commonly used Cre transgenic mouse line to study
      osteoblasts, the Osx-GFP::Cre (Osx-Cre) mice. Cortical and trabecular bone
      parameters were determined in the femurs of Osx-Cre mice at 6 and 12 weeks of age
      by microtomography (MUCT). At 6 weeks of age, Osx-Cre mice had reduced body
      weight by 22% (P < 0.0001) and delayed cortical bone expansion and accrual,
      characterized by decreases in periosteal circumference by 7% (P < 0.05) and
      cortical thickness by 11% (P < 0.01), compared to wild type controls.
      Importantly, the cortical bone phenotype of the skeletally immature Osx-Cre mice
      at 6 weeks of age could be accounted for by their low body weight. The delayed
      weight gain and cortical growth of Osx-Cre mice was overcome by 12 weeks of age,
      with no differences observed between Osx-Cre and wild type controls. In
      conclusion, Osx-Cre expressing mice display a delayed growth phenotype in the
      absence of doxycycline treatment, evidenced by decreased cortical bone expansion
      and accrual at 6 weeks of age, as an indirect result of decreased body weight.
      While this delay in growth is overcome by adulthood at 12 weeks of age, caution
      together with appropriate data analysis must be considered when assessing the
      experimental data from skeletally immature Cre/loxP knockout mice generated using
      the Osx-Cre mouse line to avoid misinterpretation.

PMID- 22160437
TI  - Remodelling of human atrial K+ currents but not ion channel expression by chronic
      beta-blockade.
AB  - Chronic beta-adrenoceptor antagonist (beta-blocker) treatment in patients is
      associated with a potentially anti-arrhythmic prolongation of the atrial action
      potential duration (APD), which may involve remodelling of repolarising K(+)
      currents. The aim of this study was to investigate the effects of chronic beta
      blockade on transient outward, sustained and inward rectifier K(+) currents
      (I(TO), I(KSUS) and I(K1)) in human atrial myocytes and on the expression of
      underlying ion channel subunits. Ion currents were recorded from human right
      atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA
      and protein levels were measured using real time RT-PCR and Western blotting.
      Chronic beta-blockade was associated with a 41% reduction in I(TO) density: 9.3
      +/- 0.8 (30 myocytes, 15 patients) vs 15.7 +/- 1.1 pA/pF (32, 14), p < 0.05;
      without affecting its voltage-, time- or rate dependence. I(K1) was reduced by
      34% at -120 mV (p < 0.05). Neither I(KSUS), nor its increase by acute beta
      stimulation with isoprenaline, was affected by chronic beta-blockade.
      Mathematical modelling suggested that the combination of I(TO)- and I(K1)
      decrease could result in a 28% increase in APD(90). Chronic beta-blockade did not
      alter mRNA or protein expression of the I(TO) pore-forming subunit, Kv4.3, or
      mRNA expression of the accessory subunits KChIP2, KChAP, Kvbeta1, Kvbeta2 or
      frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account
      for the reduction in I(K1). A reduction in atrial I(TO) and I(K1) associated with
      chronic beta-blocker treatment in patients may contribute to the associated
      action potential prolongation, and this cannot be explained by a reduction in
      expression of associated ion channel subunits.

PMID- 22160438
TI  - Electron microscopic study of mouse embryonic stem cell-derived cardiomyocytes.
AB  - Differentiation of embryonic stem cell (ESC)-derived embryoid bodies (EBs) is a
      heterogeneous process. ESCs can differentiate in vitro into different cell types
      including beating cardiomyocytes. The main aim of the present study was to
      develop an improved preparation method for scanning electron microscopic study of
      ESC-derived cardiac bundles and to investigate the fine structural
      characteristics of mouse ESCs-derived cardiomyocytes using electron microscopy.
      The mouse ESCs differentiation was induced by EBs' development through hanging
      drop, suspension and plating stages. Cardiomyocytes appeared in the EBs'
      outgrowth as beating clusters that grew in size and formed thick branching
      bundles gradually. Cardiac bundles showed cross striation even when they were
      observed under an inverted microscope. They showed a positive immunostaining for
      cardiac troponin I and alpha-actinin. Transmission and scanning electron
      microscopy (TEM & SEM) were used to study the structural characteristics of ESC
      derived cardiomyocytes. Three weeks after plating, differentiated EBs showed a
      superficial layer of compact fibrous ECM that made detailed observation of
      cardiac bundles impossible. We tried several preparation methods to remove
      unwanted cells and fibers, and finally we revealed the branching bundles of
      cardiomyocytes. In TEM study, most cardiomyocytes showed parallel arrays of
      myofibrils with a mature sarcomeric organization marked by H-bands, M-lines and
      numerous T-tubules. Cardiomyocytes were connected to each other by intercalated
      discs composed of numerous gap junctions and fascia adherences.

PMID- 22160439
TI  - Prognostic implications of chronic kidney disease and anemia after percutaneous
      coronary intervention in acute myocardial infarction patients.
AB  - Anemia is a common complication of chronic kidney disease (CKD), and a few
      studies suggest that both CKD and anemia have a marked impact on the prognosis of
      patients with cardiovascular disease. We retrospectively analyzed the prevalence
      of CKD and anemia in 312 patients with acute myocardial infarction (AMI). The
      patients were divided into four groups according to the presence of CKD and
      anemia. Chronic kidney disease was defined as estimated glomerular filtration
      rate <60 ml/min/1.73 m(2), and anemia was defined according to the World Health
      Organization definition. Of 312 AMI patients, 166 (53.2%) had CKD and 87 (27.8%)
      had anemia. A powerful relationship was observed between both CKD and anemia and
      major adverse cardiac and cerebrovascular events (MACCE) or death by any cause.
      After adjustment for comorbidities, the hazard ratio (HR) for MACCE was
      significantly higher in the anemia-only group (HR 5.42, 95% confidence interval
      (CI) 1.38-21.27, P = 0.015), the CKD-only group (HR 6.4, 95% CI 2.09-19.58, P =
      0.001), and the CKD and anemia group (HR 11.61, 95% CI 3.65-36.89, P < 0.001).
      With respect to death by any cause, the HR was significantly higher in the CKD
      only group (HR 2.68, 95% CI 1.02-7.02, P = 0.045) and the CKD and anemia group
      (HR 4.40, 95% CI 1.56-12.43, P = 0.005). One-half of the patients with AMI had
      CKD as well. Furthermore, when anemia coexisted with CKD, these conditions had a
      multiplicative amplification effect on the risk of MACCE and death by any cause
      in patients with AMI.

PMID- 22160440
TI  - Outbreak of hemolytic uremic syndrome caused by E. coli O104:H4 in Germany: a
      pediatric perspective.
AB  - In May-June 2011, an unprecedented outbreak of hemolytic uremic syndrome (HUS)
      caused by Shiga toxin-producing E. coli (STEC) O104:H4 affected >800 adults, in
      whom this disorder is usually rarely seen. Over 90 children were also affected in
      the largest STEC-associated HUS outbreak in children to date. Despite high
      patient numbers and chronic staff shortages in pediatric institutions, almost all
      patients were treated locally, mainly because of maximally increased staff input.
      Epidemiologic features were characterized by relatively high age at presentation,
      possibly related to the isolated etiologic agent, raw bean sprouts. Fortunately,
      in children, other clinical features, including neurological complications,
      dialysis requirement, and short-term outcome, were comparable to previous
      historical series. Only one child died, compared to 35 adults. Differences in
      treatment recommendations and approaches between adults and children were noted.
      Treatment with eculizumab was available, but handled more restrictively in
      children. Despite treatment differences, children and adult clinical outcomes
      were comparable, pending a final analysis. In summary the STEC O104:H4 HUS
      outbreak was challenging for pediatric resources but clinical presentation and
      complications were comparable to previous experience. Acute outbreak onset made
      structured approaches to treatments impossible, however, ongoing analysis may
      provide evidence for improving care of children with STEC HUS.

PMID- 22160441
TI  - Internalizing symptoms: effects of a preventive intervention on developmental
      pathways from early adolescence to young adulthood.
AB  - This study examined the mediated and moderated effects of a universal family
      focused preventive intervention, delivered during young adolescence, on
      internalizing symptoms assessed in young adulthood. Sixth grade students (N=446;
      52% female; 98% White) and their families from 22 rural Midwestern school
      districts were randomly assigned to the experimental conditions in 1993. Self
      report questionnaires were administered at seven time points (pre-test to young
      adulthood-age 21) to those receiving the Iowa Strengthening Families Program
      (ISFP) and to the control group. Results showed that growth factors of adolescent
      internalizing symptoms (grades 6-12) were predicted by ISFP condition and risk
      status (defined as early substance initiation). Moderation of the condition
      effect by risk status was found, with higher-risk adolescents benefitting more
      from the ISFP. Results also supported the hypothesis that the ISFP's effect on
      internalizing symptoms in young adulthood was mediated through growth factors of
      adolescents' internalizing symptoms; risk moderation, however, was only
      marginally significant in young adulthood. The relative reduction rate on
      clinical or subclinical levels of young adult internalizing symptoms was 28%,
      indicating that for every 100 young adults displaying clinical or subclinical
      levels of internalizing symptoms from school districts not offering an
      intervention, there could be as few as 72 displaying those levels of symptoms in
      school districts that offered middle school prevention programming. These
      findings highlight how the positive effects of family-focused universal
      interventions can extend to non-targeted outcomes and the related potential
      public-health impact of scaling up these interventions.

PMID- 22160442
TI  - Too much of a good thing? How breadth of extracurricular participation relates to
      school-related affect and academic outcomes during adolescence.
AB  - Although adolescents often participate in multiple extracurricular activities,
      little research has examined how the breadth of activities in which an adolescent
      is involved relates to school-related affect and academic performance. Relying on
      a large, multi-ethnic sample (N = 864; 55.9% female), the current study
      investigated linear and non-linear relationships of 11th grade activity
      participation in four activity domains (academic/leadership groups, arts
      activities, clubs, and sports) to adolescents' sense of belonging at school,
      academic engagement, and grade point average, contemporarily and in 12th grade.
      Results of multiple regression models revealed curvilinear relationships for
      sense of belonging at school in 11th and 12th grade, grade point average in 11th
      grade, and academic engagement in 12th grade. Adolescents who were moderately
      involved (i.e., in two domains) reported a greater sense of belonging at school
      in 11th and 12th grade, a higher grade point average in 11th grade, and greater
      academic engagement in 12th grade, relative to those who were more or less
      involved. Furthermore, adolescents' sense of belonging at school in 11th grade
      mediated the relationship of domain participation in 11th grade to academic
      engagement in 12th grade. This study suggests that involvement in a moderate
      number of activity domains promotes positive school-related affect and greater
      academic performance. School policy implications and recommendations are
      discussed.

PMID- 22160443
TI  - Neurotoxic sequelae of mercury exposure: an intervention and follow-up study in
      the Brazilian Amazon.
AB  - Since 1995, the Caruso Project used an Ecosystem Approach to Human Health to
      examine mercury (Hg) exposure in fish-eating communities in the Brazilian Amazon
      and develop interventions to maximise nutrition from traditional diet and
      minimise toxic risk. In 1995, 2000 and 2006, this study followed fish
      consumption, Hg levels, and visual and motor functions in 31 villagers.
      Questionnaires gathered information on socio-demographics and diet. Hair Hg (H
      Hg) levels were measured. Visual acuity, colour vision, manual dexterity and grip
      strength were assessed. Data was analysed using general linear models of repeated
      measures. Total fish consumption, similar in 1995 and 2000, decreased in 2006.
      Carnivorous fish consumption initially decreased and then remained stable,
      whereas non-carnivorous fish consumption first increased and then decreased. H-Hg
      declined from 17.6 to 7.8 MUg/g. Visual functions showed a significant decrease
      over time, with those with H-Hg >= 20 MUg/g in 1995 showing greater loss. Motor
      functions showed initial improvement and then returned to the 1995 performance
      level. Decrease in Hg exposure is attributed to the intervention and socio
      economic changes in the village. While there may be a certain reversibility of
      motor deficits, visual capacities may decrease progressively with respect to
      exposure prior to the intervention.

PMID- 22160444
TI  - Parasitic infections, anemia and malnutrition among rural settled and mobile
      pastoralist mothers and their children in Chad.
AB  - Malnutrition, resulting from various etiologies, is common in rural Chadian women
      and children. This cross-sectional study assessed the spectrum of parasitic
      infection and level of anemia and their effect on nutritional status in settled
      and mobile pastoral mothers and children near Lake Chad. Intestinal parasites
      were evaluated using direct fecal smears and the Kato-Katz technique. Malaria
      status was determined using Paracheck-Pf((r)) rapid diagnostic test, and anemia
      was assessed with the Hemocue photometer. Nutritional status was evaluated using
      anthropometric parameters. At the end of the 2008 wet season, the prevalence of
      malnutrition was 36% [confidence interval (CI) 30-42] among women and 15% (CI 11
      18) among children. The prevalence of intestinal parasitic infection was 75% (CI
      68-83) among women and 60% (CI 53-66) among children. The predominant helminth
      species was Ascaris lumbricoides while Entamoeba histolytica/dispar was the most
      common protozoan. The hookworm prevalence was 14% (CI 8-20) in women and 18% (CI
      13-23) in children. Malaria prevalence was low among women (1%, CI 0.5-2) and
      children (3% CI 2-5). No significant difference was observed in the prevalence of
      parasitic infection between the mobile pastoralist and rural sedentary
      populations. Thirty-four percent (CI 27-40) of nonpregnant women, 53% (CI 34-72)
      of pregnant women, and 27% (CI 23-32) of children were anemic. In subjects
      infected with Plasmodium, all women and 54% (CI 22-85) of children were anemic.
      Malnutrition was significantly associated with anemia in mothers and with
      selected intestinal parasites, anemia and age in their children.

PMID- 22160445
TI  - Exposure to partner, family, and community violence: gang-affiliated Latina women
      and risk of unintended pregnancy.
AB  - While teen pregnancy rates appear to be declining in the U.S.A. overall, the rate
      of decline among young Latinas has been less than other ethnic groups. Among the
      myriad factors associated with elevated pregnancy rates, for Latina girls living
      in the inner city, exposure to gang and community violence may be a critical
      context for increased pregnancy risk. This study explores the relationship
      between gang involvement and reproductive health, and the pathways through which
      childhood, family, and relationship violence exposure may lead to unintended
      pregnancy. Interviews of 20 young adult Latinas with known gang involvement in
      Los Angeles County were audiotaped, transcribed, and coded for key themes related
      to violence exposure and reproductive health. Limited access to reproductive
      health care compounded by male partner sexual and pregnancy coercion, as well as
      physical and sexual violence, emerged in the interviews. Exposures to
      interparental domestic violence, childhood physical and sexual abuse, and gang
      violence were prominent and closely associated with unhealthy and abusive
      intimate relationships. Adverse childhood experiences and exposure to partner,
      family, and community violence impact the reproductive lives and choices of young
      Latina women in gangs. These findings may guide targeted pregnancy prevention
      efforts among urban gang-affiliated Latinas as well as encourage the integration
      of sexual violence prevention and reproductive health promotion within gang
      violence intervention programs.

PMID- 22160446
TI  - Linking neighborhood characteristics to food insecurity in older adults: the role
      of perceived safety, social cohesion, and walkability.
AB  - Among the 14.6% of American households experiencing food insecurity,
      approximately 2 million are occupied by older adults. Food insecurity among older
      adults has been linked to poor health, lower cognitive function, and poor mental
      health outcomes. While evidence of the association between individual or
      household-level factors and food insecurity has been documented, the role of
      neighborhood-level factors is largely understudied. This study uses data from a
      representative sample of 1,870 New York City senior center participants in 2008
      to investigate the relationship between three neighborhood-level factors
      (walkability, safety, and social cohesion) and food insecurity among the elderly.
      Issues relating to food security were measured by three separate outcome
      measures: whether the participant had a concern about having enough to eat this
      past month (concern about food security), whether the participant was unable to
      afford food during the past year (insufficient food intake related to financial
      resources), and whether the participant experienced hunger in the past year
      related to not being able to leave home (mobility-related food insufficiency).
      Unadjusted and adjusted logistic regression was performed for each measure of
      food insecurity. Results indicate that neighborhood walkability is an important
      correlate of mobility-related food insufficiency and concern about food
      insecurity, even after controlling the effects of other relevant factors.

PMID- 22160447
TI  - A self-contained, programmable microfluidic cell culture system with real-time
      microscopy access.
AB  - Utilizing microfluidics is a promising way for increasing the throughput and
      automation of cell biology research. We present a complete self-contained system
      for automated cell culture and experiments with real-time optical read-out. The
      system offers a high degree of user-friendliness, stability due to simple
      construction principles and compactness for integration with standard
      instruments. Furthermore, the self-contained system is highly portable enabling
      transfer between work stations such as laminar flow benches, incubators and
      microscopes. Accommodation of 24 individual inlet channels enables the system to
      perform parallel, programmable and multiconditional assays on a single chip. A
      modular approach provides system versatility and allows many different chips to
      be used dependent upon application. We validate the system's performance by
      demonstrating on-chip passive switching and mixing by peristaltically driven
      flows. Applicability for biological assays is demonstrated by on-chip cell
      culture including on-chip transfection and temporally programmable gene
      expression.

PMID- 22160448
TI  - Abstracts of the 15th International Conference on Biological Inorganic Chemistry.
      August 7-12, 2011. Vancouver, British Columbia, Canada.

PMID- 22160449
TI  - The production of conjugated alpha-linolenic, gamma-linolenic and stearidonic
      acids by strains of bifidobacteria and propionibacteria.
AB  - Conjugated fatty acids are regularly found in nature and have a history of
      biogenic activity in animals and humans. A number of these conjugated fatty acids
      are microbially produced and have been associated with potent anti-carcinogenic,
      anti-adipogenic, anti-atherosclerotic and anti-diabetogenic activities.
      Therefore, the identification of novel conjugated fatty acids is highly
      desirable. In this study, strains of bifidobacteria and propionibacteria
      previously shown by us and others to display linoleic acid isomerase activity
      were assessed for their ability to conjugate a range of other unsaturated fatty
      acids during fermentation. Only four, linoleic, alpha-linolenic, gamma-linolenic
      and stearidonic acids, were converted to their respective conjugated isomers,
      conjugated linoleic acid (CLA), conjugated alpha-linolenic acid (CLNA),
      conjugated gamma-linolenic acid (CGLA) and conjugated stearidonic acid (CSA),
      each of which contained a conjugated double bond at the 9,11 position. Of the
      strains assayed, Bifidobacterium breve DPC6330 proved the most effective
      conjugated fatty acid producer, bio-converting 70% of the linoleic acid to CLA,
      90% of the alpha-linolenic acid to CLNA, 17% of the gamma-linolenic acid to CGLA,
      and 28% of the stearidonic acid to CSA at a substrate concentration of 0.3 mg mL
      1. In conclusion, strains of bifidobacteria and propionibacteria can bio-convert
      linoleic, alpha-linolenic, gamma-linolenic and stearidonic acids to their
      conjugated isomers via the activity of the enzyme linoleic acid isomerase. These
      conjugated fatty acids may offer the combined health promoting properties of
      conjugated fatty acids such as CLA and CLNA, along with those of the unsaturated
      fatty acids from which they are formed.

PMID- 22160450
TI  - Paraoxonase 1 activity in chylomicrons and VLDL: the effect of type 2 diabetes
      and meals rich in saturated fat and oleic acid.
AB  - Paraoxonase 1 (PON 1) has antioxidant and cardioprotective properties and is
      abnormally low in type 2 diabetic serum. This study aimed to determine the effect
      of type 2 diabetes and meals rich in saturated fat and oleic acid on PON1
      activity in chylomicrons and very low density lipoproteins (VLDL). PON1
      arylesterase activity was measured in chylomicrons and VLDL that were isolated in
      serum from 20 patients with type 2 diabetes and 20 age- and gender-matched,
      overweight controls 3 h after meals rich in cream or olive oil in a randomized,
      cross-over study. Chylomicron-PON1 activity (45%, P = 0.02), ratio chylomicron
      PON1/chylomicron-triacylglycerides (TAG) (42%, P = 0.03) and chylomicron-protein
      content (46%, P < 0.001) were significantly lower in patients with type 2
      diabetes compared with controls after the olive oil meal with comparable findings
      after the meal rich in cream. After ingestion of olive oil, chylomicron-PON1
      activity was significantly higher in controls (P = 0.01) and marginally higher (P
      = 0.06) in diabetic patients and chylomicron-TAG were significantly (P < 0. 05)
      higher in both groups of subjects, compared with values after ingestion of cream.
      VLDL-PON1 increased (two-fold) significantly (P < 0.003) during both meals.
      Chylomicron-PON1 activity was correlated significantly with chylomicron-protein
      (P < 0.001, n = 40) and with postprandial serum PON1 activity (P <= 0.001, n =
      40). Our data suggest that type 2 diabetes is associated with abnormally low
      chylomicron-PON1 activity after fatty meals and this may be linked to lower
      chylomicron-protein content and serum PON1 activity. Switching from saturated fat
      to olive oil in the meal increases PON1 activity in the chylomicron fraction
      largely due to increased numbers of chylomicron particles.

PMID- 22160452
TI  - Learning to define myself.

PMID- 22160451
TI  - Aberrations in plasma phospholipid fatty acids in lung cancer patients.
AB  - Abnormalities in lipid metabolism have been frequently observed in cancer and are
      associated with a poor prognosis. However, a detailed, longitudinal
      characterization of fatty acid status is lacking. This study aimed to assess
      plasma phospholipid fatty acids before chemotherapy, immediately after and 1
      month following chemotherapy in a group of 50 patients newly diagnosed with lung
      cancer and explore factors which may contribute to aberrations in fatty acids.
      Their mean +/- SD characteristics: age 64 +/- 8.5 years, 75% advanced stage
      disease, body mass index 27.0 +/- 5.4 kg/m2, 6 month weight loss -4.6 +/- 6.1%.
      Compared to patients with early stage disease, patients with advanced disease had
      abnormal fatty acid profiles including significantly lower (P < 0.05) amounts of
      total phospholipid fatty acids, saturated, and polyunsaturated fatty acids
      (linoleic, arachidonic, eicosapentaenoic and docosahexaenoic). Longitudinal
      analysis revealed that patients with advanced disease who completed chemotherapy
      had stable fatty acid levels and continued to maintain levels 1 month following
      completion of chemotherapy. Comparatively, patients who did not complete
      chemotherapy due to toxicity or disease progression had progressive loss of total
      phospholipid fatty acids, stearic, linoleic and n-6 fatty acids and a trend
      towards lower docosahexaenoic, arachidonic, palmitic, n-3 and saturated fatty
      acids. These results suggest that loss of fatty acids is prevalent, progressive
      and potentially influenced by advanced disease and chemotherapy treatment.

PMID- 22160453
TI  - "Sometimes, it's hard to be a parent".

PMID- 22160455
TI  - Development of respiratory trees in the holothurian Apostichopus japonicus
      (Aspidochirotida: Holothuroidea).
AB  - The development of respiratory trees in the holothurian Apostichopus japonicus
      has been studied using light and electron microscopy. Primordial respiratory
      trees emerge in 2-3-mm-long animals (2 months after fertilization). They arise as
      two independent outgrowths from the dorsal wall of the anterior part of the
      cloaca. Upon first emerging and throughout the course of development, the left
      respiratory tree is longer than the right one. A common base develops in 4-mm
      long animals (2-3 months after fertilization). In yearlings, the left respiratory
      tree grows into gaps between the loops of the intestinal tube interlaced with
      intestinal hemal vessels. The developing coelomic and luminal epithelia have
      ultrastructural peculiarities. The luminal epithelium of respiratory trees has
      been shown for the first time to comprise nerve cells and their processes.
      Characteristic structural features of the epithelia are shown to begin developing
      as early as in 4-mm-long animals (2-3 months after fertilization). In yearlings,
      the respiratory trees demonstrate definitive structural patterns and are entirely
      functional.

PMID- 22160456
TI  - Morphological and immunohistochemical characterisation of the thymus in juvenile
      turbot (Psetta maxima, L.).
AB  - We performed structural and immunohistochemical studies on the thymus of juvenile
      turbot (Psetta maxima L.) in order to define its cellular composition. The thymic
      stroma was mainly composed of two subpopulations of reticulo-epithelial cells
      (RECs). RECs immunoreactive to anti-actin antibody were distributed through the
      organ, while RECs that were cytokeratin-immunopositive were located in the outer
      zone of the thymus. The parenchyma of the thymus was composed of several cell
      types such as lymphocytes/thymocytes, lymphoblasts, melano-macrophages and to a
      lesser extent of nurse-like cells, immunoglobulin positive (Ig+) cells, mucous
      cells, rodlet cells and neuroendocrine cells. CD3epsilon+ lymphocytes were mainly
      located in the outer zone. On the other hand, Ig+ cells were observed in the
      transitional region between the inner and outer zones of the thymus. The
      neuroendocrine cells were large and exhibited immunoreactivity to neuropeptide Y
      and vasoactive intestinal polypeptide. They were located in the inner zone of the
      thymus in close association with lymphoblasts and lymphocytes/thymocytes. This
      work provides useful information on the structure and cellular composition of the
      thymus of turbot, identifying several immunomarkers that allow the identification
      of different cell types, providing the basis for further studies on the immune
      response of turbot against diseases.

PMID- 22160457
TI  - IL-17 and FGF signaling involved in mouse mesenchymal stem cell proliferation.
AB  - The mouse is a suitable experimental model to study the biology of mesenchymal
      stem cells (MSCs), as well as to be used in biocompatibility studies and tissue
      engineering models. However, the isolation and purification of murine MSCs is far
      more challenging than their counterparts from other species. In this study, we
      isolated, expanded and characterized mouse MSCs from bone marrow (BM-MSCs).
      Additionally, we analyzed the effects of two regulatory molecules, interleukin 17
      (IL-17) and basic fibroblast growth factor (bFGF), on BM-MSCs growth and
      elucidated the signaling pathways involved. The results revealed that IL-17
      increased the frequency of colony-forming units fibroblast (CFU-F) as well as the
      BM-MSCs proliferation in a dose-dependent manner, while bFGF supplementation had
      no significant effect on CFU-F frequency but induced an increase in cell
      proliferation. Their combined usage did not produce additive effects on BM-MSCs
      proliferation and even induced reduction in the number of CFU-F. Also, the
      involvement of both p38 and extracellular signal-regulated kinase (ERK) mitogen
      activated protein kinases (MAPKs) signaling in proliferative activity of IL-17
      and bFGF on murine BM-MSCs and, moreover, the increased co-activation of a common
      signaling molecule, p38 MAPK, were demonstrated. Together, the data presented
      highlighted the role of IL-17 and bFGF in murine BM-MSCs proliferation and
      pointed to the complexity and specificity of the signaling networks leading to
      MSCs proliferation in response to different regulatory molecules.

PMID- 22160458
TI  - Functional dissimilarity of melanomacrophage centres in the liver and spleen from
      females of the teleost fish Prochilodus argenteus.
AB  - Melanomacrophage centres (MMCs) are formed by macrophage aggregates containing
      pigments such as hemosiderin, melanin and lipofuscin. MMCs are found in animals
      such as reptiles, amphibians and, mainly, fishes, in organs such as the kidney,
      spleen, thymus and liver. In teleost fish, several functions have been attributed
      to MMCs, including the capture and storage of cations, the phagocytosis of
      cellular debris and immunological reactions. As the use of MMCs has been
      suggested as a tool for the assessment of environmental impacts, our aim has been
      to describe the various metabolic processes performed by MMCs in diverse organs
      (liver and spleen) by using the teleost Prochilodus argenteus as an animal model.
      MMCs from the liver and spleen were assessed by histochemistry, transmission
      electron microscopy, scanning electron microscopy, X-ray microanalysis techniques
      and biochemical assay for N-acetylglucosaminidase activity. The data showed
      metabolic differences in MMCs between the liver and spleen of P. argenteus in
      their morphometric characteristics and biochemical and elemental composition. The
      implications of these findings are discussed, focusing on their role in organ
      metabolism.

PMID- 22160459
TI  - LINE-1 retrotransposition in human neuroblastoma cells is affected by oxidative
      stress.
AB  - Long interspersed element-1s (LINE-1 or L1s) are abundant retrotransposons that
      occur in mammalian genomes and that can cause insertional mutagenesis and genomic
      instability. L1 activity is generally repressed in most cells and tissues but has
      been found in some embryonic cells and, in particular, in neural progenitors.
      Moreover, L1 retrotransposition can be induced by several DNA-damaging agents. We
      have carried out experiments to verify whether L1 retrotransposition is affected
      by oxidative DNA damage, which plays a role in a range of human diseases,
      including cancer and inflammatory and neurodegenerative disease. To this purpose,
      BE(2)C neuroblastoma cells, which are thought to represent embryonic precursors
      of sympathetic neurons, have been treated with hydrogen peroxide and subjected to
      an in vitro retrotransposition assay involving an episomal L1(RP) element tagged
      with enhanced green fluorescent protein. Our results indicate that hydrogen
      peroxide treatment induces an increase in the retrotransposition of transiently
      transfected L1(RP) and an increase in the expression of endogenous L1
      transcripts. An increase of gamma-H2AX foci and changes in the mRNA levels of
      MRE11, RAD50, NBN and ERCC1 (all involved in DNA repair) have also been found.
      Thus, oxidative stress can cause L1 dysregulation.

PMID- 22160460
TI  - Coronates, spherical containers, bowl-shaped surfaces, porous 1D-, 2D-, 3D
      metallo-coordination polymers, and metallodendrimers.
AB  - Supramolecular coordination cages and polymers bear exceptional advantages over
      their organic counterparts. They are available in one-pot reactions and in high
      yields and display physical properties that are generally inaccessible with
      organic species. Moreover, their weak, reversible, noncovalent bonding
      interactions facilitate error checking and self-correction. This review
      emphasizes the achievements in supramolecular coordination container as well as
      polymer chemistry initiated by serendipity and their materialization based on
      rational design. The recognition of similarities in the synthesis of different
      supramolecular assemblies allows prediction of potential structures in related
      cases. The combination of detailed symmetry considerations with the basic rules
      of coordination chemistry has only recently allowed for the design of rational
      strategies for the construction of a variety of nanosized spherical containers,
      bowls, 1D-, 2D-, and 3D-coordination polymers with specified size and shape.

PMID- 22160461
TI  - Protein structure determination by solid-state NMR.
AB  - Membrane proteins are a large, diverse group of proteins, representing about 20
      30% of the proteomes of most organisms, serving a multitude of cellular functions
      and more than 40% of drug targets. Knowledge of a membrane protein structure
      enables us insight into its function and dynamics, and can be used for further
      rational drug design. Owing to the intrinsic hydrophobicity, flexibility, and
      instability of membrane proteins, solid-state NMR may offer an unique opportunity
      to study membrane protein structure, ligand binding, and activation at atomic
      resolution in the native membrane environment on a wide ranging time scale. Over
      the past several years, solid-state NMR has made tremendous progress, showing its
      capability of determining membrane protein structure, ligand binding, and protein
      dynamic conformation on a variety of time scales at atomic resolution. In this
      chapter we will mainly discuss some recent achievements on membrane protein
      structure determination, ligand conformation and binding, structure changes upon
      activation, and structure of insoluble fibrous proteins investigated by using
      magic-angle spinning solid-state NMR from the structural biology point of view.
      Protein dynamics, sensitivity enhancement, and the possibility of chemical shift
      based structure determination in solid-state NMR are also briefly touched upon.

PMID- 22160462
TI  - Key outcomes are usually not reported in published fracture secondary prevention
      programs: results of a systematic review.
AB  - OBJECTIVE: A secondary analysis of a systematic review on interventions to
      improve osteoporosis (OP) investigation and treatment was conducted to examine
      reported key outcomes: (1) the cost of the intervention; (2) the proportion of
      patients taking OP medication beyond 6 months of the intervention; and (3) the
      proportion of patients who re-fractured. METHODS: Fifty-seven articles reporting
      on 54 studies (64 interventions) from 11 countries were included. Intervention
      studies to improve OP management were eligible if they were conducted in an
      orthopedic setting and included primary data on >=20 patients presenting with a
      hip fracture or any fragility fracture. To compare outcome data across all
      interventions regardless of study design, an equated proportion (EP) using a
      denominator based on the intention-to-treat principle was derived. Whether a cost
      analysis had been conducted, the EP of patients who were taking medication beyond
      6 months of the intervention, and the EP of patients who re-fractured during the
      study period were documented. RESULTS: Of the 54 studies, 2 reported a cost
      analysis and demonstrated that the interventions were at least cost-effective.
      The EP for medication use beyond 6 months of the intervention ranged from 17 to
      56% for four studies. The EP for re-fracture ranged from 0 to 5% for four
      studies. CONCLUSION: Most interventions did not report key outcomes. In addition,
      authors used varying time frames for re-fracture and medication use, making
      direct comparisons impossible. Authors should consider including intervention
      costs, medication use beyond 6 months of the intervention, and re-fracture data
      in future fracture secondary prevention programs.

PMID- 22160463
TI  - Stress-inducible expression of barley Hva1 gene in transgenic mulberry displays
      enhanced tolerance against drought, salinity and cold stress.
AB  - Coping with different kinds of biotic and abiotic stresses is the foundation of
      sustainable agriculture. Although conventional breeding and marker-assisted
      selection are being employed in mulberry (Morus indica L.) to develop better
      varieties, nonetheless the longer time periods required for these approaches
      necessitates the use of precise biotechnological approaches for sustainable
      agriculture. In an attempt to improve stress tolerance of mulberry, an important
      plant of the sericulture industry, an encoding late embryogenesis abundant gene
      from barley (HVA1) was introduced into mulberry plants by Agrobacterium-mediated
      transformation. Transgenic mulberry with barley Hva1 under a constitutive
      promoter actin1 was shown to enhance drought and salinity tolerance. Here, we
      report that overexpression of barley Hva1 also confers cold tolerance in
      transgenic mulberry. Further, barley Hva1 gene under control of a stress
      inducible promoter rd29A can effectively negate growth retardation under non
      stress conditions and confer stress tolerance in transgenic mulberry. Transgenic
      lines display normal morphology to enhanced growth and an increased tolerance
      against drought, salt and cold conditions as measured by free proline, membrane
      stability index and PSII activity. Protein accumulation was detected under stress
      conditions confirming inductive expression of HVA1 in transgenics. Investigations
      to assess stress tolerance of these plants under field conditions revealed an
      overall better performance than the non-transgenic plants. Enhanced expression of
      stress responsive genes such as Mi dnaJ and Mi 2-cysperoxidin suggests that Hva1
      can regulate downstream genes associated with providing abiotic stress tolerance.
      The investigation of transgenic lines presented here demonstrates the acquisition
      of tolerance against drought, salt and cold stress in plants overexpressing
      barley Hva1, indicating that Arabidopsis rd29A promoter can function in mulberry.

PMID- 22160464
TI  - Effect of estrogen priming through luteal phase and stimulation phase in poor
      responders in in-vitro fertilization.
AB  - PURPOSE: To verify whether a novel protocol administering E(2) during the luteal
      phase of the preceding cycle and during ovarian stimulation in GnRH antagonist
      cycle could enhance follicular response and hence improve outcomes in poor
      responders. METHODS: In this retrospective analysis, a total of 155 poor
      responder patients subjected to IVF/ICSI were analyzed. All the patients had
      history of more than one prior IVF cycle failure with poor response (less than 5
      oocytes retrieved and/or maximal E2 level less than 500 pg/mL) by using
      conventional long agonist or antagonist protocol. In luteal E2 treatment protocol
      (n = 86), oral estradiol valerate 4 mg/day was initiated on luteal day 21 and
      either stopped at menstrual cycle day 3 (Protocol A, n = 28) or continued during
      the period of ovarian stimulation until the day of hCG injection (Protocol B, n =
      58). IVF parameters and pregnancy outcome of luteal E2 treatments group were
      compared with a standard GnRH antagonist protocol (n = 69) which the patients
      received no hormonal pretreatment. RESULTS: Compared to standard GnRH antagonist
      protocol, cancellation rate was lower with luteal E2 group (15.1% vs 37.7%, p <
      0.01). Moreover, patients treated with luteal estrogen resulted in an increased
      number of oocytes retrieved (4.5 +/- 2.9 vs 3.2 +/- 1.9; p < 0.01). A trend
      toward increase in number of normally fertilized embryos (2.9 +/- 2.1vs 2.3 +/-
      1.9; p = 0.043), and increased prevalence of good quality embryos (51.2% vs 25%;
      p = 0.047) were noted. Comparing protocol A and B, there were no significant
      difference between embryologic data, however there were slight increase in
      ongoing pregnancy rate in protocol B compared to A (27.1% vs 20%, p = 0.357),
      although statistical significance was not achieved. CONCLUSION: Estrogen priming
      through luteal phase and stimulation phase improved ovarian responsiveness and
      this may lead to an increase in pregnancy rate in poor responders with failed
      cycle.

PMID- 22160465
TI  - Genomic organization, phylogenetic comparison and differential expression of the
      SBP-box family of transcription factors in tomato.
AB  - SBP-box genes represent transcription factors ubiquitously found in the plant
      kingdom and recognized as important regulators of many different aspects of plant
      development. In this study, 15 SBP-box gene family members were identified in
      tomato and analyzed with respect to their genomic organization and other
      structural features. Phylogenetic reconstruction based on the DNA-binding SBP
      domain, allowed the classification of the SlySBP proteins into eight groups
      representing clear orthologous relationships to family members of other flowering
      plants and the moss Physcomitrella. In order to have a better understanding of
      their possible function in the development of a fleshy-fruit species like tomato,
      the mRNA expression levels of all SlySBP genes were quantified in vegetative and
      reproductive organs of plants, at different stages of growth. As transcripts of
      ten SlySBP genes were found to carry putative miR156- and miR157-response
      elements, the expression levels of the corresponding microRNAs were determined as
      well, revealing different patterns of expression. In addition, eight putative
      miR156 and four miR157 encoding loci could be identified in the tomato genome,
      four of them forming a polycistronic cluster. Whereas miR156 and miR157 levels
      were highest in seedlings, leaves and anthers of young flowers, most miR156
      targeted SlySBP genes were found to be expressed in young inflorescences and
      during fruit development and ripening, suggesting a particularly important role
      during tomato reproductive growth. The data presented provide a basis for future
      clarification of the various functions that SBP-box gene family members play in
      tomato growth and development.

PMID- 22160466
TI  - Decreased microglial activation in MS patients treated with glatiramer acetate.
AB  - Activated microglia are thought to be an important contributor to tissue damage
      in multiple sclerosis (MS). The level of microglial activation can be measured
      non-invasively using [(11)C]-R-PK11195, a radiopharmaceutical for positron
      emission tomography (PET). Prior studies have identified abnormalities in the
      level of [(11)C]-R-PK11195 uptake in patients with MS, but treatment effects have
      not been evaluated. Nine previously untreated relapsing-remitting MS patients
      underwent PET and magnetic resonance imaging of the brain at baseline and after 1
      year of treatment with glatiramer acetate. Parametric maps of [(11)C]-R-PK11195
      uptake were obtained for baseline and post-treatment PET scans, and the change in
      [(11)C]-R-PK11195 uptake pre- to post-treatment was evaluated across the whole
      brain. Region-of-interest analysis was also applied to selected subregions. Whole
      brain [(11)C]-R-PK11195 binding potential per unit volume decreased 3.17% (95%
      CI: -0.74, -5.53%) between baseline and 1 year (p = 0.018). A significant
      decrease was noted in cortical gray matter and cerebral white matter, and a trend
      towards decreased uptake was seen in the putamen and thalamus. The results are
      consistent with a reduction in inflammation due to treatment with glatiramer
      acetate, though a larger controlled study would be required to prove that
      association. Future research will focus on whether the level of baseline
      microglial activation predicts future tissue damage in MS and whether [(11)C]-R
      PK11195 uptake in cortical gray matter correlates with cortical lesion load.

PMID- 22160467
TI  - Characterization and expression of attacin, an antibacterial protein-encoding
      gene, from the beet armyworm, Spodoptera exigua (Hubner) (Insecta: Lepidoptera:
      Noctuidae).
AB  - To isolate antimicrobial-related genes from the beet armyworm, Spodoptera exigua,
      we performed GeneFishing, a polymerase chain reaction (PCR)-based differential
      display technique. An attacin-like complementary DNA (cDNA) including a 3'
      untranslated region was identified from among 18 over-expressed genes in
      microbial-infected larvae. The full-length attacin cDNA from S. exigua cDNA
      (Seattacin) was cloned using rapid amplification of cDNA ends PCR. The attacin
      like cDNA transcript was 765 nucleotides in length, and the predicted polypeptide
      was 254 amino acids in length with a calculated molecular mass of 27.6 kDa and an
      isoelectric point of 6.44. The protein sequence of the attacin-like cDNA showed
      high identity to that of Trichoplusia ni (61.2%). The amino acid sequence
      identity of Seattacin to the orthologous proteins in Bombyx mori, Manduca sexta,
      Heliothis virescens, Hlicoverpa armigera, Hyphantria cunea, Hyalophora cecropia,
      and Drosophila melanogaster was 61.2, 46.1, 44.5, 42.2, 39.5, 45.1, and 24.0%,
      respectively. To examine possible immune functions of the attacin-like cDNA, its
      expression was investigated by reverse transcriptase PCR analysis after
      challenging S. exigua with microorganisms. The attacin-like cDNA was expressed at
      high levels 12 h post-infection, and its expression was slightly induced 4-8 h
      post-infection compared to control larvae inoculated with sterile water.
      Furthermore, induced Seattacin showed biological activity against several
      bacteria including Escherichia coli DH5alpha, Pseudomonas cichorii, Bacillus
      subtilis, and Listeria monocytogenes. These results suggest that the attacin-like
      cDNA of S. exigua codes for antimicrobial peptides.

PMID- 22160468
TI  - A novel mutation (Cys308Phe) of the LDL receptor gene in families from the South
      Eastern part of Poland.
AB  - The purpose of this investigation was to characterize a new mutation in the LDL
      receptor (LDLR) gene in three families with clinically diagnosed familial
      hypercholesterolemia (FH) from the South-Eastern part of Poland. Mutational
      screening with exon by exon sequencing analysis was performed in all probands.
      The novel mutation c986G>T (Cys308Phe) in the exon 7 of LDLR gene was found in
      three apparently unrelated probands with FH. Analysis of the receptor activity of
      peripheral blood lymphocytes by binding and uptake of DiL-LDL showed a
      significant reduction (by 24% versus healthy control) of the fluorescent label in
      the lymphocytes of patients heterozygous for this mutation. Concentrations of
      serum LDL-C in probands before treatment were between 9.5 and 10.5 mmol/l. All
      patients had corneal arcus and tendon xanthoma. Clinically, families were
      characterized by premature coronary artery disease. This mutation occurred
      relatively frequently in our group of patients with FH, but this could be
      explained by a founder effect since we demonstrated their common ancestors.

PMID- 22160469
TI  - Role of NYGGF4 in insulin resistance.
AB  - Insulin resistance is a clinical condition that is characterized by reducing
      glucose uptake in response to insulin. A major factor in the development of
      insulin resistance syndrome is obesity. NYGGF4 is a novel gene that is abundantly
      expressed in the adipose tissue of obese subjects. NYGGF4 induced the secretion
      of FFAs and TNF-alpha and caused mitochondrial dysfunction, which may cause
      insulin resistance. This review will summarize the effect of NYGGF4 on the
      adipogenesis, glucose uptake and mitochondrial dysfunction in vitro, and the
      possible mechanism and signal pathway of NYGGF4 for insulin resistance.

PMID- 22160470
TI  - Identification of an intronic cis-acting element in the human dopamine
      transporter gene.
AB  - The human dopamine transporter gene (hDAT) encodes the dopamine transporter in
      dopamine (DA) neurons to regulate DA transmission. hDAT expression varies
      significantly from neuron to neuron, and from individual to individual so that
      dysregulation of hDAT is related to many neuropsychiatric disorders. It is
      critical to identify hDAT-specific cis-acting elements that regulate the hDAT
      expression. Previous studies showed that hDAT Intron 1 displayed inhibitory
      activity for reporter gene expression. Here we report that the hDAT Intron 1
      contains a 121-bp fragment that down-regulated both SV40 and hDAT promoter
      activities by 80% in vitro. Subfragments of 121-bp still down-regulated the SV40
      promoter but not the hDAT promoter, as supported by nuclear protein-binding
      activities. Collectively, 121-bp is a silencer in vitro that might coordinate
      with transcriptional activities both inside and outside 121-bp in regulation of
      hDAT.

PMID- 22160471
TI  - Interleukin 1 beta -511 C/T gene polymorphism and susceptibility to febrile
      seizures: a meta-analysis.
AB  - One previous meta-analysis found no evidence that interleukin 1 beta (IL-1beta) 
      511 gene polymorphism was associated with febrile seizures (FS) by pooling a
      limited number of studies. However, it is necessary for the meta-analysis to
      reevaluate the relationship with more recent findings. Electronic databases were
      systematically searched for studies published before June 2011. Pooled odds
      ratios (OR) and 95% confidence interval (CI) were estimated by means of a genetic
      model free approach. Subgroup and sensitivity analyses were also performed. All
      statistical analyses were conducted using Stata 9.0. A total of eight studies,
      728 FS cases and 1,223 controls, met the selection criteria. The results show a
      significant association between IL-1beta -511 C/T gene polymorphism and FS
      (recessive genetic model TT vs. CC + CT: OR = 1.361, 95% CI: 1.065-1.738, P =
      0.014). Subgroup analyses show a significant association in Asia (OR = 1.394, 95%
      CI: 1.005-1.935, P = 0.047), but not in Europe (OR = 1.387, 95% CI: 0.750-2.565,
      P = 0.298). IL-1beta -511 C/T gene polymorphism may play a role in susceptibility
      to FS, especially in Asia. Geographic differences may be a critical factor in the
      risk of FS.

PMID- 22160472
TI  - Molecular cloning and functional characterization of Catharanthus roseus
      hydroxymethylbutenyl 4-diphosphate synthase gene promoter from the methyl
      erythritol phosphate pathway.
AB  - The Madagascar periwinkle produces monoterpenoid indole alkaloids (MIA) of high
      interest due to their therapeutical values. The terpenoid moiety of MIA is
      derived from the methyl erythritol phosphate (MEP) and seco-iridoid pathways.
      These pathways are regarded as the limiting branch for MIA biosynthesis in C.
      roseus cell and tissue cultures. In previous studies, we demonstrated a
      coordinated regulation at the transcriptional and spatial levels of genes from
      both pathways. We report here on the isolation of the 5'-flanking region (1,049
      bp) of the hydroxymethylbutenyl 4-diphosphate synthase (HDS) gene from the MEP
      pathway. To investigate promoter transcriptional activities, the HDS promoter was
      fused to GUS reporter gene. Agrobacterium-mediated transformation of young
      tobacco leaves revealed that the cloned HDS promoter displays a tissue-specific
      GUS staining restricted to the vascular region of the leaves and limited to a
      part of the vein that encompasses the phloem in agreement with the previous
      localization of HDS transcripts in C. roseus aerial organs. Further functional
      characterizations in stably or transiently transformed C. roseus cells allowed us
      to identify the region that can be consider as the minimal promoter and to
      demonstrate the induction of HDS promoter by several hormonal signals (auxin,
      cytokinin, methyljasmonate and ethylene) leading to MIA production. These
      results, and the bioinformatic analysis of the HDS 5'-region, suggest that the
      HDS promoter harbours a number of cis-elements binding specific transcription
      factors that would regulate the flux of terpenoid precursors involved in MIA
      biosynthesis.

PMID- 22160473
TI  - Heavy metal contamination in feathers of Western Reef Heron (Egretta gularis) and
      Siberian gull (Larus heuglini) from Hara biosphere reserve of Southern Iran.
AB  - The main objectives of article were monitor the metal concentrations of cadmium,
      lead, copper, zinc, cobalt, and iron, in the feather of shorebirds species,
      Western Reef Heron (Egretta gularis) and Siberian Gull (Larus heuglini) from Hara
      Biosphere Reserve of Southern Iran; and identify any relationships between
      species. Assaying heavy metals by using Shimadzu AA 680 flame atomic absorption
      spectrophotometer, the results were given as micrograms per gram dry weight. The
      concentrations of heavy metal were found to follow the order of
      iron>zinc>copper>lead>cadmium>cobalt for E. gularis and of
      iron>zinc>lead>copper>cadmium>cobalt for L. heuglini. Also, they showed that the
      cadmium, copper, and cobalt concentrations were higher in females than in the
      males, while the lead concentration for E. gularis and L. heuglini was higher in
      males. The cadmium concentration means they were measured as1.16 and 1.37 MUg/g
      for E. gularis and L. heuglini, respectively, whereas the lead concentration
      means 7.04 and 5.48 MUg/g for E. gularis and L. heuglini, respectively. The
      concentrations of nonessential trace elements in E. gularis and L. heuglini were
      generally comparable to values reported in other studies. The average levels of
      lead we observed in these birds were greater than 5 MUg/g dry weight in the
      feather that is known to be associated with adverse behavioral or reproductive
      effects. Data analysis showed that there was a positive correlation between
      copper and zinc (P < 0.01), copper and cobalt (P < 0.05).

PMID- 22160474
TI  - Estimation of 210Po and 210Pb and its dose to human beings due to consumption of
      marine species of Ennore Creek, South India.
AB  - A systemic study on the natural radionuclides such as (210)Po and (210)Pb in the
      environmental matrices and biota of Ennore Creek has been undertaken to establish
      a baseline data on the radiation profile of Ennore Creek environment. The
      environmental samples such as water, sediment, and biota (seaweeds, molluscs,
      crustaceans, and fishes) have been subjected to analyses. It has been observed
      that the concentration of (210)Po and (210)Pb in the water samples of Ennore
      Creek as 2.7 and 1.63 m Bq L(-1), respectively. The activity concentration of
      (210)Po and (210)Pb in the sediment sample was 17.9 and 28.9 Bq kg(-1),
      respectively. The bivalve mollusk Perna viridis have been identified to
      accumulate higher concentrations of (210)Po and (210)Pb suggesting that they
      could serve as bioindicator of radionuclides in the Ennore Creek environment. The
      committed effective dose for human beings was found at 81.13-216.8 and 2.1-297.2
      MUSv year(-1) for (210)Po and (210)Pb, respectively.

PMID- 22160475
TI  - The impact of traditional coffee processing on river water quality in Ethiopia
      and the urgency of adopting sound environmental practices.
AB  - Although waste from coffee processing is a valuable resource to make biogas,
      compost, and nutrient-rich animal food, it is usually dumped into nearby water
      courses. We carried out water quality assessment at 44 sampling sites along 18
      rivers that receive untreated waste from 23 coffee pulping and processing plants
      in Jimma Zone, Ethiopia. Twenty upstream sampling sites free from coffee waste
      impact served as control, and 24 downstream sampling sites affected by coffee
      waste were selected for comparison. Physicochemical and biological results
      revealed a significant river water quality deterioration as a result of disposing
      untreated coffee waste into running water courses. During coffee-processing (wet)
      season, the highest organic load (1,900 mg/l), measured as biochemical oxygen
      demand, depleted dissolved oxygen (DO) to a level less than 0.01 mg/l, and thus
      curtailed nitrification. During off season, oxygen started to recuperate and
      augmented nitrification. The shift from significantly elevated organic load and
      reduced DO in the wet season to increased nitrate in the off season was found to
      be the determining factor for the difference in macroinvertebrate community
      structure as verified by ordination analysis. Macroinvertebrate diversity was
      significantly reduced in impacted sites during the wet season contrary to the off
      season. However, there was a significant difference in the ratio of sensitive to
      pollution-tolerant taxa in the off season, which remained depreciated in the
      longer term. This study highlights the urgency of research exploring on the
      feasibility of adopting appropriate pollution abatement technologies to implement
      ecologically sound coffee-processing systems in coffee-growing regions of
      Ethiopia.

PMID- 22160476
TI  - Multimodality treatment approach in children with cerebral arteriovenous
      malformation--a survey in the Danish population.
AB  - INTRODUCTION: Arteriovenous malformations are not a common disease in childhood.
      A national survey was conducted to reveal the Danish incidence of the disease,
      presentation, choice of treatment, and outcome. MATERIALS AND METHODS: Forty
      patients were admitted to any of the five neurosurgical centers during the years
      2000-2008. A retrospective survey was conducted using hospital records. RESULTS:
      Twenty-three males and 17 females presented with AVM with a mean age of 11.3 (1
      month-18 years). The incidence was found to be 0.4/100,000. Early fatal outcome
      was seen in three patients. Treatment was surgery (12), endovascular (5),
      radiosurgery (6), or a combination of the above (10). Four patients were treated
      conservatively. Complications of the treatment were seen in 27%. Occlusion rate
      was 74%. Good or excellent outcome was seen in 65%. CONCLUSION: A national survey
      may give a lower rate of success than in the specialized centers accepting
      patients more eligible for treatment. Still, the low number of children could
      call for centralization and collaboration in this population.

PMID- 22160477
TI  - Subcutaneous blood patch for iatrogenic suboccipital pseudomeningocele following
      decompressive suboccipital craniectomy and enlarging duroplasty for the treatment
      of Chiari I malformation. Technical note.
AB  - PURPOSE: Epidural blood patch (EBP) represents one of the best nonsurgical
      treatment for intracranial hypotension syndrome. Orthostatic headache caused by
      reduced intracranial cerebrospinal fluid (CSF) pressure, like in "spontaneous"
      intracranial hypotension or as consequence of lumbar puncture or
      anesthesiological procedure, can be managed with the injection of autologous
      blood on the epidural space with a successful rate of 89%, increased to 97% after
      a second application. MATERIALS AND METHODS: This 9-year-old girl was admitted to
      our department because of a suboccipital pseudomeningocele. She was previously
      operated on for a Chiari type I malformation by suboccipital craniectomy, C1
      laminectomy and duraplasty. At the admission, she complained for nucal pain.
      Brain MRI showed a large suboccipital fluid collection that persisted even after
      the revision of the duraplasty and the placement of an external lumbar drainage.
      The child underwent a first injection of a mixture of blood (10 ml) and fibrin
      glue (10 ml) within the subcutaneous space after needle-aspiration of the
      collection. The same treatment was repeated 3 weeks later. RESULTS: The
      procedures were well tolerated and no local or systemic complications occurred.
      The fluid collection was significantly reduced after the first injection and it
      was completely effaced following the second one. Such a result remained stable
      after 3 months, as demonstrated by MRI. No recurrence of the pseudomeningocele
      was detected at the last clinical control (8-month follow-up). CONCLUSION:
      Subcutaneous blood patch could represent a safe and effective option for the
      treatment of CSF fistula, especially in case of failure of the traditional
      management.

PMID- 22160478
TI  - Intracranial, supratentorial dermoid cysts in paediatric patients--two cases and
      a review of the literature.
AB  - BACKGROUND: Intracranial dermoid cysts are rare space-occupying lesions in
      paediatric patients. Supratentorial or lateralized localisations are described
      even less frequently. Diagnosis may be hard to obtain using standard imaging.
      Surgical removal provides cure for these benign, but growing lesions. METHODS: We
      describe the cases of two paediatric patients in which supratentorially located
      (one lateralized) dermoid cysts were diagnosed and operated on. Due to unusual
      presenting symptoms, diagnosis was not straightforward in these cases. Complete
      resection could be achieved in both patients without any neurological sequelae.
      We reviewed the current literature available on dermoid cysts in paediatric
      patients which comprises mainly case reports and only two series. We could
      identify a total of 61 patients harbouring dermoid cysts. Only ten of these were
      located supratentorially, and only one was lateralized. DISCUSSION: Most of the
      midline dermoids were associated with a dermal sinus. Complete surgical removal
      was discussed as the only treatment option in all cases. Difficulties in
      diagnosis were reported frequently. Despite good availability of routine MR
      imaging, the diagnosis of a dermoid cysts, probably due to the low incidence,
      still remains a challenge. These lesions represent benign intracranial masses.
      Yet non-neoplastic, they can lead to neurological deficits due to their space
      occupying effect. CONCLUSIONS: Radical surgical resection, if feasible without
      major risk for the patient, remains the only option of cure. Due to their unusual
      position and their unique symptomatology, our cases add favourably to the current
      literature, showing, once more, the multiple facets of this disease.

PMID- 22160480
TI  - Endoscopic therapy for Barrett's esophagus: a review of its emerging role in
      optimal diagnosis and endoluminal therapy.
AB  - Barrett's esophagus (BE) is a premalignant lesion known to sequentially progress
      to esophageal adenocarcinoma. Management of BE has changed significantly over the
      last 5 years with the development of endoscopic resection and ablation, which has
      replaced esophagectomy as the treatment of choice in BE with high-grade
      dysplasia. The aim of this review is to discuss the details of these new
      endotherapies in regards to response and durability and to define the role of
      these new therapies in the current management of BE.

PMID- 22160481
TI  - Multi-person sex among a sample of adolescent female urban health clinic
      patients.
AB  - Adolescent sexual activity involving three or more people is an emerging public
      health concern. The goal of this exploratory, cross-sectional study was to
      describe the prevalence, correlates, and context of multiple-person sex among a
      sample of adolescent females seeking health care from an urban clinic. Because
      sex involving multiple people may either be consensual (i.e., "three-ways" or
      "group sex") or forced (i.e., "gang rape"), we use the term "multi-person sex"
      (MPS) to encompass these experiences. Subjects were 328 females, ages 14-20 years
      old, who utilized a Boston-area community- or school-based health clinic between
      April and December of 2006, and completed an anonymous survey using computer
      assisted self-interview software. Overall, 7.3% reported ever having had a MPS
      experience. Of these, 52% reported ever being pressured to engage in MPS and 43%
      reported ever being threatened or forced. Condom nonuse by at least one male
      participant in the most recent MPS was reported by 45%. Controlling for potential
      demographic confounders, MPS was associated with cigarette smoking (adjusted
      prevalence ratio [APR], 3.83; 95% confidence interval [CI], 1.56-9.44), sexual
      initiation prior to age 15 (APR, 2.50; 95% CI, 1.04-5.98), ever being diagnosed
      with an STI (APR, 2.55; 95% CI, 1.08-6.03), dating violence victimization (APR,
      4.43; 95% CI, 1.68-11.69), childhood sexual abuse victimization (APR, 4.30; 95%
      CI, 1.83-10.07) and past-month pornography exposure (APR, 4.79; 95% CI, 1.91
      11.98). Additional study of the perpetration and prevention of adolescent MPS is
      urgently needed.

PMID- 22160482
TI  - A small molecule screening strategy with validation on human leukemia stem cells
      uncovers the therapeutic efficacy of kinetin riboside.
AB  - Gene regulatory networks that govern hematopoietic stem cells (HSCs) and leukemia
      initiating cells (L-ICs) are deeply entangled. Thus, the discovery of compounds
      that target L-ICs while sparing HSC is an attractive but difficult endeavor.
      Presently, most screening approaches fail to counter-screen compounds against
      normal hematopoietic stem/progenitor cells (HSPCs). Here, we present a multistep
      in vitro and in vivo approach to identify compounds that can target L-ICs in
      acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel
      leukemia cell lines derived from human experimental leukemogenesis models yielded
      80 hits, of which 10 were less toxic to HSPC. We characterized a single compound,
      kinetin riboside (KR), on AML L-ICs and HSPCs. KR demonstrated comparable
      efficacy to standard therapies against blast cells in 63 primary leukemias. In
      vitro, KR targeted the L-IC-enriched CD34(+)CD38(-) AML fraction, while sparing
      HSPC-enriched fractions, although these effects were mitigated on HSC assayed in
      vivo. KR eliminated L-ICs in 2 of 4 primary AML samples when assayed in vivo and
      highlights the importance of in vivo L-IC and HSC assays to measure function.
      Overall, we provide a novel approach to screen large drug libraries for the
      discovery of anti-L-IC compounds for human leukemias.

PMID- 22160484
TI  - Development of disposable PDMS micro cell culture analog devices with
      photopolymerizable hydrogel encapsulating living cells.
AB  - Microscale cell culture devices with two or more cell types, such as the micro
      cell culture analog (microCCA), are promising devices to predict mammalian
      response to toxic drug and chemical exposure. A polydimethylsiloxane (PDMS)
      version of such microfluidic devices has been challenging to construct due to the
      difficulty of patterning multi cell types directly into designated individual
      cell culture chambers in an oxygen plasma bonded PDMS device. Approaches with
      micro-valves for flow control are complex, expensive and inconvenient to use. In
      this study, an alternative approach using polyethylene glycol diacrylate (PEG-DA)
      for spatially controlled multi-cell type patterning inside a bonded microCCA
      device is described. We constructed a three-cell type PDMS microCCA following a
      human physiologically based pharmacokinetic (PBPK) modeling, and applied
      continuous cell culture medium recirculation within the device as a blood
      surrogate. A fluorescence microscope based direct pattern writing method was used
      to form cell/hydrogel microstructures with higher cell viability than the
      traditional UV lamp based method. The positive effect of mixed molecular weight
      PDG-DA on hydrogel-encapsulated cell membrane integrity was also studied. This
      prototype PDMS microCCA device was then tested with Triton X-100 as a model
      toxicant. The combination of hydrogel photo-patterning and the microfluidic cell
      culture platform enables the fabrication of simple and low cost multi-cell type
      biosensors for drug development, toxicity study and clinical diagnosis.

PMID- 22160483
TI  - Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia:
      2-year follow-up from a randomized phase 3 trial (DASISION).
AB  - Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and
      safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia
      (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase
      (CP) CML were randomized to receive dasatinib 100 mg (n = 259) or imatinib 400 mg
      (n = 260) once daily. Primary data showed superior efficacy for dasatinib
      compared with imatinib after 12 months, including significantly higher rates of
      complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and
      major molecular response (MMR). Here, 24-month data are presented. Cumulative
      response rates by 24 months in dasatinib and imatinib arms were: CCyR in 86%
      versus 82%, MMR in 64% versus 46%, and BCR-ABL reduction to <= 0.0032% (4.5-log
      reduction) in 17% versus 8%. Transformation to accelerated-/ blast-phase CML on
      study occurred in 2.3% with dasatinib versus 5.0% with imatinib. BCR-ABL
      mutations, assessed after discontinuation, were detected in 10 patients in each
      arm. In safety analyses, fluid retention, superficial edema, myalgia, vomiting,
      and rash were less frequent with dasatinib compared with imatinib, whereas
      pleural effusion and grade 3/4 thrombocytopenia were more frequent with
      dasatinib. Overall, dasatinib continues to show faster and deeper responses
      compared with imatinib, supporting first-line use of dasatinib in patients with
      newly diagnosed CML-CP. This study was registered at ClinicalTrials.gov:
      NCT00481247.

PMID- 22160485
TI  - Hematologic outcomes and blood utilization in cancer patients with chemotherapy
      induced anemia (CIA) pre- and post-national coverage determination (NCD): results
      from a multicenter chart review.
AB  - PURPOSE: In July 2007, the Centers for Medicare and Medicaid Services (CMS)
      limited coverage of erythropoiesis-stimulating agents (ESAs) in cancer patients
      with chemotherapy-induced anemia (CIA) through a National Coverage Determination
      (NCD). The primary objective of this study was to compare transfusion rates in
      patients with CIA with lung, breast, or colorectal cancer before and after the
      NCD. METHODS: Adult Medicare patients with CIA treated at 49 community oncology
      clinics were selected from two time periods based on clinics' NCD implementation
      date. Chart data were abstracted for 12 weeks post-CIA episode start, defined as
      hemoglobin (Hb) level <11 g/dL while receiving chemotherapy or within 60 days of
      the last chemotherapy dose. Multivariate analyses were used to calculate the odds
      of transfusion and to assess the units of blood transfused, controlling for
      differences in demographics, clinical history, and chemotherapy. RESULTS: Eight
      hundred pre-NCD and 994 post-NCD patients from 49 sites were selected. Of the
      patients, 56% used ESAs post-NCD vs. 88% pre-NCD (p < 0.0001). The duration of
      ESA use decreased in the post-NCD (32.1 days) vs. pre-NCD (48.4 days, p < 0.0001)
      group. The post-NCD group reported significantly lower Hb levels, higher odds of
      receiving a transfusion (odds ratio: 1.41, 95% CI 1.05-1.89, p = 0.0238) and
      increased blood utilization of 53% (units transfused: OR 1.53, 95% CI 1.15-2.04,
      p = 0.0034). CONCLUSIONS: Decreased frequency and duration of ESA administration
      were reported in the post-NCD vs. pre-NCD period. Findings were accompanied by a
      modest but statistically significant increase in transfusions and a decrease in
      Hb values.

PMID- 22160486
TI  - Engineering of a phosphorylatable tag for specific protein binding on zirconium
      phosphonate based microarrays.
AB  - A phosphorylatable tag was designed and fused at the C-terminal end of proteins,
      which allowed efficient and oriented immobilization of capture proteins on glass
      substrates coated with a zirconium phosphonate monolayer. The concept is
      demonstrated using Nanofitin directed against lysozyme. This peptide tag
      (DSDSSSEDE) contains four serines in an acidic environment, which favored its in
      vitro phosphorylation by casein kinase II. The resulting phosphate cluster at the
      C-terminal end of the protein provided a specific, irreversible, and multipoint
      attachment to the zirconium surface. In a microarray format, the high surface
      coverage led to high fluorescence signal after incubation with Alexa Fluor 647
      labeled lysozyme. The detection sensitivity of the microarray for the labeled
      target was below 50 pM, owing to the exceptionally low background staining, which
      resulted in high fluorescence signal to noise ratios. The performance of this new
      anchoring strategy using a zirconium phosphonate modified surface compares
      favorably with that of other types of microarray substrates, such as
      nitrocellulose-based or epoxide slides, which bind proteins in a nonoriented way.

PMID- 22160487
TI  - Nicotinic acetylcholine receptor expression on B-lymphoblasts of healthy versus
      schizophrenic subjects stratified for smoking: [3H]-nicotine binding is decreased
      in schizophrenia and correlates with negative symptoms.
AB  - Heavy smoking and schizophrenia are diversely associated with nicotinic
      acetylcholine receptor expression, as was shown for brain and lymphocytes. Most
      studies so far have not systematically differentiated between schizophrenia
      smokers and non-smokers and were confined either to in vivo or post-mortem study
      approaches. In order to avoid variable in vivo influences or post-mortem bias, we
      used stably transformed B-lymphoblast cultures derived from healthy and
      schizophrenia subjects stratified for smoking versus non-smoking in order to
      differentiate these clinical conditions with regard to nicotinic acetylcholine
      receptor expression and regulation. Receptor quantities were measured using
      [(3)H]-nicotine and [(3)H]-epibatidine binding. At baseline, [(3)H]-nicotine
      binding was not statistically different between healthy smokers and never-smokers
      (1.59 +/- 0.73 vs. 1.26 +/- 0.91 fmol/10(6) cells), while it was reduced in
      schizophrenia smokers compared to healthy smokers (1.05 +/- 0.69 fmol vs. 1.44 +/
      0.84/10(6) cells, P = 0.01). In schizophrenia, baseline [(3)H]-nicotine
      correlated inversely with higher PANSS negative subscale scores. After long-term
      nicotine incubation (1 MUM), [3H]-nicotine binding increased in the group of
      schizophrenia smokers only (from 1.05 +/- 0.69 to 1.54 +/- 0.77 fmol/106 cells, P
      = 0.013), while [(3)H]-epibatidine binding decreased in this group (4.52 +/- 1.52
      to 3.82 +/- 1.38 fmol/10(6) cells, P = 0.038). Our data are in further support of
      a decrease of nicotinic acetylcholine receptor expression in schizophrenia linked
      to negative psychotic symptoms, which may be counter-regulated by nicotine
      exposure.

PMID- 22160488
TI  - Effect of the calcineurin inhibitor FK506 on K+-Cl- cotransporter 2 expression in
      the mouse hippocampus after kainic acid-induced status epilepticus.
AB  - Calcineurin (CaN)-mediated excitotoxicity impairs gamma-aminobutyric acid (GABA)
      transmission and induces neuronal apoptosis. Ca(2+)-dependent K(+)-Cl(-)
      cotransporter 2 (KCC2) participates in GABAergic inhibitory transmission.
      However, the mechanism by which CaN mediates GABA receptor-mediated KCC2 in
      seizures is not fully understood. In the present study, we investigated the
      altered expression of KCC2 and the effects of the CaN inhibitor FK506 on KCC2
      expression in the mouse hippocampus following kainic acid (KA) treatment. FK506
      was injected twice 24 h and 30 min before KA treatment and then mice were treated
      with KA and killed 2 days later. FK506 had anticonvulsant effect on KA-induced
      seizure activities. CaN cleavage was evident in the hippocampus 24 h after KA
      treatment. FK506 pretreatment blocked the truncation of CaN in the KA-treated
      hippocampus. Cresyl violet and TUNEL staining showed that FK506 prevented KA
      induced hippocampal cell death. In particular, Western blot analysis showed that
      KCC2 expression was time dependent, with a peak at 6 h and a return to decreased
      levels at 48 h, whereas FK506 pretreatment inhibited the KA-induced decrease in
      KCC2 expression in the hippocampus. Immunofluorescence showed that FK506
      pretreatment protected the loss of inhibitory GABAergic KCC2-expressing neurons
      following KA treatment. Taken together, these results provide evidence that
      altered KCC2 expression may be associated with Ca(2+)-mediated seizure activity
      and indicate that neuron-specific KCC2 may be involved in neuroprotection after
      seizures.

PMID- 22160489
TI  - Cannabinoid modulation of subgenual anterior cingulate cortex activation during
      experience of negative affect.
AB  - Cannabinoids affect positive and negative affective experience and emotional
      perception, possibly by modulating limbic brain reactivity. In this double-blind
      crossover, placebo-controlled functional magnetic resonance imaging study in
      humans, an acute oral dose of ?(9)-tetrahydrocannabinol (THC) attenuated
      subgenual anterior cingulate cortex (sgACC) reactivity during the induction of
      negative affect. This observation extends prior findings implicating a cortico
      limbic, emotion-related central mechanism underlying cannabinoid function.

PMID- 22160490
TI  - Kynurenines and the nervous system: therapeutic perspectives.

PMID- 22160491
TI  - Multiple brain abscess from dental origin: case report and literature review.
AB  - BACKGROUND: Brain abscess of dental origin is a rare situation and deserves
      attention due to its high mortality rate even when adequate treatment is done.
      Few reports are available when dental origin is the main cause of this infection.
      CASE REPORT: We present the case of a 70-year-old man diagnosed with cerebral
      abscess caused by apical lesions located at superior and inferior teeth. The
      three lesions containing pus were drained from anterior and posterior brain
      region and the laboratory evaluation revealed the presence of Streptococcus
      viridians and Bacteroides. Postoperative period was uneventful with excellent
      recovery after 1 year of surgery. Final diagnosis was able to be done due to
      excellent image exams availability like computer tomography and magnetic
      resonance using diffusion and perfusion techniques. DISCUSSION: The early
      detection of this pathology with the correct diagnosis essential to give the
      patient the best treatment including antimicrobial drugs and drainage is of
      extreme importance.

PMID- 22160492
TI  - The impact of population-based screening studies on hemochromatosis screening
      practices.
AB  - OBJECTIVES: To determine if community population screening studies for
      hemochromatosis affected HFE genetic screening practices in non-study
      populations. METHODS: An audit of all genetic testing for HFE mutations at London
      Health Sciences Center, London, Ontario, Canada from 1997 to 2010 was performed.
      The frequency of genetic testing and the frequency of C282Y homozygous cases
      identified during the years of the London Red Cross (1998-1999) and HEIRS (2000
      2005) screening studies were compared with the corresponding frequencies in the
      specified years outside this range (1997-1998 and 2006-2010). RESULTS: An
      increase in HFE gene mutation testing is seen during the London Red Cross study,
      and the frequency of testing rose further during the HEIRS study. Genetic
      screening activity continued to increase in the years after publication of the
      HEIRS study. The proportion of patients with homozygosity for C282Y mutation
      remained relatively constant despite fluctuations in numbers of persons screened
      per annum. CONCLUSIONS: The rise in HFE gene testing among non-study populations
      during the HH studies could be explained by the Hawthorne effect, a phenomenon
      referring to the improvement or modification of behavior by a population as a
      consequence of it being studied. In this case, we postulate that primary care
      physicians at our center performed more HFE gene tests for their patients as a
      consequence of being affected by knowledge of the screening studies. Despite a
      general increase in testing during and after completion of the studies, the total
      number of hemochromatosis cases (C282Y homozygotes) diagnosed per annum remained
      relatively constant.

PMID- 22160493
TI  - PSS-3D1D: an improved 3D1D profile method of protein fold recognition for the
      annotation of twilight zone sequences.
AB  - Annotation of any newly determined protein sequence depends on the pairwise
      sequence identity with known sequences. However, for the twilight zone sequences
      which have only 15-25% identity, the pair-wise comparison methods are inadequate
      and the annotation becomes a challenging task. Such sequences can be annotated by
      using methods that recognize their fold. Bowie et al. described a 3D1D profile
      method in which the amino acid sequences that fold into a known 3D structure are
      identified by their compatibility to that known 3D structure. We have improved
      the above method by using the predicted secondary structure information and
      employ it for fold recognition from the twilight zone sequences. In our Protein
      Secondary Structure 3D1D (PSS-3D1D) method, a score (w) for the predicted
      secondary structure of the query sequence is included in finding the
      compatibility of the query sequence to the known fold 3D structures. In the
      benchmarks, the PSS-3D1D method shows a maximum of 21% improvement in predicting
      correctly the alpha + beta class of folds from the sequences with twilight zone
      level of identity, when compared with the 3D1D profile method. Hence, the PSS
      3D1D method could offer more clues than the 3D1D method for the annotation of
      twilight zone sequences. The web based PSS-3D1D method is freely available in the
      PredictFold server at http://bioinfo.bdu.ac.in/servers/ .

PMID- 22160494
TI  - N-acyl taurines are anti-proliferative in prostate cancer cells.
AB  - Endocannabinoids have been implicated in cancer development and cause
      heterogenous effects in tumor cells, by inducing apoptosis, reducing migration,
      causing anti-angiogenic activity and alterations in the cell cycle resulting in
      growth arrest. Recently, several novel amides of fatty acids that are
      structurally related to endocannabinoids have been isolated from mammalian
      sources, although the functions of these fatty amides are not well studied. One
      group of these novel fatty acid amides are the N-acyl taurines (fatty acids
      conjugated to the amino acid taurine). This study examined if N-acyl taurines,
      specifically N-arachidonoyl taurine and N-oleoyl taurine could function in a
      similar way to endocannabinoids and result in cell cycle alterations or growth
      arrest in the human prostate adenocarcinoma cell line PC-3. PC-3 cells were
      treated with various concentrations of N-arachidonoyl taurine and N-oleoyl
      taurine and cell proliferation and viability was measured using resazurin and
      colony formation assays. Effects of N-acyl taurines on the cell cycle was
      measured using FACS analysis. Treatment with N-arachidonoyl taurine and N-oleoyl
      taurine resulted in a significant reduction in proliferation of PC-3 cells, even
      at concentrations as low as 1 MUM. Treatment with N-oleoyl taurine resulted in an
      increased number of cells in the subG1 population, suggesting apoptosis, and a
      lower number of cells in S-phase of the cell cycle. In summary, our results show
      that novel biologically active lipids, the N-acyl taurines, result in reduced
      proliferation in PC-3 cells.

PMID- 22160495
TI  - Fish oil supplementation improves neutrophil function during cancer chemotherapy.
AB  - Cancer chemotherapy is associated with neutropenia and impaired neutrophil
      function. This study aimed to investigate whether supplementation with low dose
      fish oil (FO), providing n-3 polyunsaturated fatty acids, in cancer patients
      receiving chemotherapy after surgical tumor (mainly gastrointestinal) removal is
      able to improve the function of blood neutrophils. Patients (n = 38) receiving
      chemotherapy (5-fluorouracil and leucovorin) were randomized into two groups; one
      group (control) did not receive a supplement, while the other group (FO) received
      2 g FO/day for 8 weeks; the FO provided 0.3 g eicosapentaenoic acid plus 0.4 g
      docosahexaenoic acid per day. Patients in the control group lost an average of
      2.5 kg of weight over the 8 weeks of the study. The number of blood
      polymorphonuclear cells (PMNC), mainly neutrophils, and their functions
      (phagocytosis and hydrogen peroxide production) decreased in the control group
      (average decreases of approximately 30, 45 and 17%, respectively). FO prevented
      these decreases and actually increased body weight (average of 1.7 kg weight
      gain; p < 0.002 vs. control group), PMNC number (average 29% increase),
      phagocytosis (average 14% increase) and superoxide production (average 28%
      increase). FO may be useful in preventing chemotherapy-induced decline in
      neutrophil number and function.

PMID- 22160496
TI  - The revised Atlanta classification for acute pancreatitis: a CT imaging guide for
      radiologists.
AB  - Accurate diagnosis and description of the various findings in acute pancreatitis
      is important for treatment. The original Atlanta classification for acute
      pancreatitis sought to create a uniform system for classifying the severity of
      acute pancreatitis as well as common language to describe the various events that
      can occur in acute pancreatitis. The goal was to allow accurate communication
      between physicians using standardized language so correct treatment options could
      be used. Since that time, advances in the understanding of acute pancreatitis as
      well as improvements in both interventions and imaging have led to criticisms of
      the system and its abandonment by physicians. A 2007 revision of the Atlanta
      classifications sought to address many of these issues. This article will explain
      the changes to the Atlanta classification system and provide pictorial examples
      of the findings in acute pancreatitis as described by the Atlanta classification
      system.

PMID- 22160497
TI  - Giving and withholding of information following genomic screening: challenges
      identified in a study of primary care physicians in Estonia.
AB  - The use of predictive genomic information to improve medical care remains a
      contentious topic. However, it is generally agreed that the potential of genomics
      to improve medicine relies on medical care providers' ability to effectively
      communicate and put in context the meaning of test results. As the amount of
      information available increasingly outstrips providers' ability to offer
      qualified judgments on what the information means, consumers inevitably will be
      faced with test results of uncertain significance, as well as difficult questions
      about what they do or do not wish to know. Results of this survey of 64 primary
      care doctors in Estonia suggests that it may be inherently difficult for
      physicians to withhold genetic information obtained by genome scans or
      sequencing, even when they believe that having that information is not in the
      best interests of their patient. The descriptive data suggest introducing genomic
      medicine through primary care physicians, as proposed by the Estonian Genome
      Center of the University of Tartu, will require further genetics education as
      well as a carefully developed set of guidelines for determining where, when and
      how to use test results.

PMID- 22160498
TI  - Discovering resilience.

PMID- 22160499
TI  - Evaluating a session--punitive vs. reflective.

PMID- 22160500
TI  - Sesuvium portulacastrum (L.) L.: a potential halophyte for the degradation of
      toxic textile dye, Green HE4B.
AB  - Sesuvium portulacastrum is a common halophyte growing well in adverse
      surroundings and is exploited mainly for the environmental protection including
      phytoremediation, desalination and stabilization of contaminated soil. In the
      present investigation, attempts have been made on the decolorization of a toxic
      textile dye Green HE4B (GHE4B) using in vitro grown Sesuvium plantlets. The
      plantlets exhibited significant (70%) decolorization of GHE4B (50 mg l(-1)) that
      sustain 200 mM sodium chloride (NaCl) within 5 days of incubation. The enzymatic
      analysis performed on the root and shoot tissues of the in vitro plantlets
      subjected to GHE4B decolorization in the presence of 200 mM NaCl showed a
      noteworthy induction of tyrosinase, lignin peroxidase and NADH-DCIP reductase
      activities, indicating the involvement of these enzymes in the metabolism of the
      dye GHE4B. The UV-visible spectrophotometer, HPLC and Fourier Transform Infrared
      Spectroscopy (FTIR) analyses of the samples before and after decolorization of
      the dye confirmed the efficient phytotransformation of GHE4B in the presence of
      200 mM NaCl. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis of the
      products revealed the formation of three metabolites such as p -amino benzene, p 
      amino toluene and 1, 2, 7-amino naphthalene after phytotransformation of GHE4B.
      Based on the FTIR and GC-MS results, the possible pathway for the biodegradation
      of GHE4B in the presence of 200 mM NaCl has been proposed. The phytotoxicity
      experiments confirmed the non-toxicity of the degraded products. The present
      study demonstrates for the first time the potential of Sesuvium for the efficient
      degradation of textile dyes and its efficacy on saline soils contaminated with
      toxic compounds.

PMID- 22160501
TI  - High biological variability of plastids, photosynthetic pigments and pigment
      forms of leaf primordia in buds.
AB  - To study the formation of the photosynthetic apparatus in nature, the carotenoid
      and chlorophyllous pigment compositions of differently developed leaf primordia
      in closed and opening buds of common ash (Fraxinus excelsior L.) and horse
      chestnut (Aesculus hippocastanum L.) as well as in closed buds of tree of heaven
      (Ailanthus altissima P. Mill.) were analyzed with HPLC. The native organization
      of the chlorophyllous pigments was studied using 77 K fluorescence spectroscopy,
      and plastid ultrastructure was investigated with electron microscopy. Complete
      etiolation, i.e., accumulation of protochlorophyllide, and absence of
      chlorophylls occurred in the innermost leaf primordia of common ash buds. The
      other leaf primordia were partially etiolated in the buds and contained
      protochlorophyllide (0.5-1 MUg g(-1) fresh mass), chlorophyllides (0.2-27 MUg g(
      1) fresh mass) and chlorophylls (0.9-643 MUg g(-1) fresh mass). Etio-chloroplasts
      with prolamellar bodies and either regular or only low grana were found in leaves
      having high or low amounts of chlorophyll a and b, respectively. After bud break,
      etioplast-chloroplast conversion proceeded and the pigment contents increased in
      the leaves, similarly to the greening processes observed in illuminated etiolated
      seedlings under laboratory conditions. The pigment contents and the ratio of the
      different spectral forms had a high biological variability that could be
      attributed to (i) various light conditions due to light filtering in the buds
      resulting in differently etiolated leaf primordia, (ii) to differences in the
      light-exposed and inner regions of the same primordia in opening buds due to
      various leaf folding, and (iii) to tissue-specific slight variations of plastid
      ultrastructure.

PMID- 22160502
TI  - Protein myozap--a late addition to the molecular ensembles of various kinds of
      adherens junctions.
AB  - The protein myozap, a polypeptide of 54 kDa, has recently been identified as a
      component of the cytoplasmic plaques of the composite junctions (areae
      compositae) in the myocardiac intercalated disks and of the adherens junctions
      (AJs) in vascular endothelia. Now we report that using very sensitive new
      antibodies and drastic localization methods, we have also identified this protein
      as a component of the AJ plaques in simple and complex epithelia, in the
      adluminal cell layer of the transitional epithelium of the urinary tract and in
      certain cell layers of diverse stratified epithelia, including gingiva, tongue,
      pharynx and esophagus, cervix, vagina and epidermis. Myozap has not been
      identified in desmosomal and tight junction plaques. We have also detected
      protein myozap in AJ structures of carcinomas. The discovery of a novel major
      protein in AJ plaques now calls for re-examinations of molecular interactions in
      AJ formation and maintenance and also offers a new marker for diagnostic
      immunocytochemistry. We also discuss the need for progressive unravelling,
      extractive treatments and buffer rinses of sections and cultured cells to reveal
      obscured or masked antigens, before definitive negative conclusions in
      immunohistochemistry can be made.

PMID- 22160503
TI  - Lions and tigers and bears, oh my! Three barriers to progress in computer-aided
      molecular design.
AB  - The computational chemistry and cheminformatics community faces many challenges
      to advancing the state of the art. We discuss three of those challenges here:
      accurately estimating the contribution of entropy to ligand binding; reliably
      estimating the uncertainties in model predictions for new molecules; and being
      able to effectively curate the ever-expanding literature and commercial databases
      needed to build new models.

PMID- 22160504
TI  - Visualizing the hill of vision in 3D using the free programming language 'R'.

PMID- 22160506
TI  - Reply to the letter by Zhang and Hoffman: Relationship between femtosecond laser
      parameters and quality of the corneal stromal bed surface.

PMID- 22160505
TI  - Intraocular pressure correlates with optic nerve sheath diameter in patients with
      normal tension glaucoma.
AB  - PURPOSE: 1. Identify differences in optic nerve sheath diameter (ONSD) as an
      indirect measure of intracranial pressure (ICP) in glaucoma patients and a
      healthy population. 2. Identify variables that may correlate with ONSD in primary
      open-angle glaucoma (POAG) and normal tension glaucoma (NTG) patients. METHODS:
      Patients with NTG (n = 46) and POAG (n = 61), and healthy controls (n = 42)
      underwent B-scan ultrasound measurement of ONSD by an observer masked to the
      patient diagnosis. Intraocular pressure (IOP) was measured in all groups, with
      additional central corneal thickness (CCT) and visual field defect measurements
      in glaucomatous patients. Only one eye per patient was selected. Kruskal-Wallis
      or Mann-Whitney were used to compare the different variables between the
      diagnostic groups. Spearman correlations were used to explore relationships among
      these variables. RESULTS: ONSD was not significantly different between healthy,
      NTG and POAG patients (6.09 +/- 0.78, 6.03 +/- 0.69, and 5.71 +/- 0.83
      respectively; p = 0.08). Visual field damage and CCT were not correlated with
      ONSD in either of the glaucoma groups (POAG, p = 0.31 and 0.44; NTG, p = 0.48 and
      0.90 respectively). However, ONSD did correlate with IOP in NTG patients (r =
      0.53, p < 0.001), while it did not in POAG patients and healthy controls (p =
      0.86, p = 0.46 respectively). Patient's age did not relate to ONSD in any of the
      groups (p > 0.25 in all groups). CONCLUSIONS: Indirect measurements of ICP by
      ultrasound assessment of the ONSD may provide further insights into the
      retrolaminar pressure component in glaucoma. The correlation of ONSD with IOP
      solely in NTG patients suggests that the translaminar pressure gradient may be of
      particular importance in this type of glaucoma.

PMID- 22160507
TI  - Single-session combined photodynamic therapy with verteporfin and intravitreal
      anti-vascular endothelial growth factor therapy for chronic central serous
      chorioretinopathy: a pilot study at 12-month follow-up.

PMID- 22160508
TI  - Combination of vitrectomy, IVTA, and laser photocoagulation for diabetic macular
      edema unresponsive to prior treatments; 3-year results.
AB  - PURPOSE: To evaluate the long-term effects of combined therapy of vitrectomy,
      intravitreal triamcinolone, and macular laser photocoagulation on diabetic
      macular edema (DME) unresponsive to prior treatment. METHODS: Medical records of
      46 eyes of 41 subjects who underwent sequential combined therapy consisting of
      vitrectomy, intravitreal triamcinolone, and macular laser photocoagulation for
      refractory DME of non-tractional origin were reviewed. Best-corrected visual
      acuity (BCVA), central subfield thickness (CST) of macula, and number of
      additional treatments were analyzed. RESULTS: Forty eyes of 35 patients completed
      a 3-year follow-up. The mean (+/- SD) CSTs before and 6 months, 1 year, 2 years,
      and 3 years after the administration of combined therapy in these eyes were 499.1
      +/- 174.9, 224.2 +/- 110.2, 273.4 +/- 173.5, 237.5 +/- 84.2 and 219.4 +/- 66.6
      um, respectively (p < 0.001). The mean (+/- SD) logMAR BCVA before and 6 months,
      1 year, 2 years, and 3 years after the combined therapy were 0.82 +/- 0.32, 0.69
      +/- 0.40, 0.63 +/- 0.39, 0.61 +/- 0.46, and 0.55 +/- 0.44, respectively (p <
      0.001). Thirty-one of 40 eyes (77.5%) exhibited no recurrence of DME after the
      combined therapy. No visually significant complications other than progression of
      lens opacity and elevation of intraocular pressure were noted during the study
      period. CONCLUSIONS: This study demonstrated the long-term stability and efficacy
      of the combined therapy described herein for the treatment of refractory DME.

PMID- 22160509
TI  - A novel germline SDHB mutation in a gastrointestinal stromal tumor patient
      without bona fide features of the Carney-Stratakis dyad.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchyme neoplasms
      of the gastrointestinal tract. Gain-of-function somatic mutations of the KIT or
      PDGFRA genes represent the most prevalent molecular alterations in GISTs. In
      Carney-Stratakis dyad, patients portray germline mutations of the succinate
      dehydrogenase subunits B (SDHB), C (SDHC) and D (SDHD) and develop multifocal
      GISTs and multicentric paragangliomas (PGLs). We herein report a novel germline
      SDHB mutation (c.T282A--Ile44Asn) occurring in a 26 years-old patient diagnosed
      with a spindle cell intermediate risk GIST that did not present KIT/PDGFRA/BRAF
      gene mutations. Further analyses revealed loss of the wild-type SDHB allele and
      complete loss of SDHB expression in the tumor tissue. After genetic screening of
      other family members, we detected in the patient's mother a SDHB mutation without
      any clinical/laboratorial evidence of GIST or PGL. Altogether, our findings
      (germline SDHB mutation with absence of PGL in the index case and of GIST and/or
      PGL in his mother) raise the possibility that this familiar setting corresponds
      to an incomplete phenotype of the Carney-Stratakis dyad.

PMID- 22160510
TI  - Detection of stapylococcal enterotoxin, methicillin-resistant and Panton
      Valentine leukocidin genes in coagulase-negative staphylococci isolated from cows
      and ewes with subclinical mastitis.
AB  - Coagulase-negative staphylococci (CNS) are the most prevalent mastitis pathogens.
      However, virulence characteristics of CNS have not been well determined. The
      presence of genes for enterotoxins (sea-sej), toxic shock syndrome toxin-1 (tst),
      the exfoliative toxins (eta, etb), Panton-Valentine leukocidin (pvl) and mecA of
      CNS species isolated from cows and ewes with subclinical mastitis was
      investigated in this study. A total of 121 CNS (81 cows, 40 ewes) representing 18
      different Staphylococci species were examined by PCR, and 38.1% (33 cows and 13
      ewes) of CNS isolates had one or more se genes. The difference between
      percentages for SE toxin genes of CNS strains isolated from cows (40.7%) and ewes
      (32.5%) was not statistically significant (P > 0.05; chi(2) = 0.380). It was
      found that S. simulans isolates had the highest prevalent se genes. Furthermore,
      the most common SE gene types was seh-sej. In this study, none of the isolates
      harbored the toxic shock syndrome toxin gene (tsst) and the exfoliative toxin
      genes (eta, etb). Five cow (6.17%) and three ewe CNS (7.5%) isolates had mecA
      gene. Three cow (3.7%) and two ewe CNS (5.0%) isolates had pvl gene. In
      conclusion, the present study showed that CNS species isolated from cows and ewes
      could serve as potential reservoir of se, mecA, and pvl genes.

PMID- 22160511
TI  - Smallholder goat breeding and flock management practices in the central rift
      valley of Ethiopia.
AB  - The study was conducted in the central rift valley of Ethiopia to define Arsi
      Bale goat keepers' breeding objectives and breeding practices and to describe
      flock management practices and rate of inbreeding in Arsi-Bale goat population.
      Two-stage sampling techniques were employed to select study sites and 202
      respondents. Semistructured questionnaire and group discussion were used to
      collect the required information. Data were analyzed using statistical package
      for social science. Rate of inbreeding in the population and indices were also
      calculated. On average, each respondent holds around 12 goats in which 30.7, 66.6
      and 2.7% were males, females and castrates, respectively. The most important
      purpose of goat production in the study area was for milk utilization. Farmers
      have multiple breeding objectives and they considered both subjective and
      objective selection criteria with slightly more emphasis on morphological
      characteristics for buck selection than replacement doe selection. Only 39.1% (n
      = 79) of respondents have their own breeding bucks. None of the respondents
      practiced controlled mating. Average rate of inbreeding in the population was
      around 0.20. Arsi-Bale goats are found to be adaptive to the prevailing
      condition. Therefore, any breed improvement strategy to be designed or
      implemented in the study area and other similar areas should consider important
      traditional breeding practices.

PMID- 22160512
TI  - Systematic review of cemented versus uncemented hemiarthroplasty for displaced
      femoral neck fractures in older patients.
AB  - The purpose of this review was to assess the effectiveness and safety of cemented
      versus uncemented hemiarthroplasty for displaced femoral neck fractures in older
      patients. We searched the Cochrane Library, MEDLINE and EMBASE for published
      randomized clinical trials comparing cemented with uncemented hemiarthroplasty
      for femoral neck fractures. Eight trials assessing 1,175 hips were eligible for
      meta-analysis. The pooled results showed that there was no significant difference
      between cemented and uncemented group with regard to the mortality, reoperation
      rates and postoperational complications. The overall incidence of residual pain
      at 1 year after operation was 23.6% in the cemented prosthesis and 34.4% in the
      uncemented, with significant difference (relative risk 0.69, 95% CI 0.53-0.90; P
      = 0.007; fixed-effect models).The available evidence suggested that compared with
      uncemented hemiarthroplasty, cemented hemiarthroplasty in treating the elderly
      with displaced femoral neck fractures was not associated with a higher risk of
      mortality, reoperation and complications but can reduce the risk of residual pain
      and provide better functional results.

PMID- 22160513
TI  - Follow-up investigation of open trigger digit release.
AB  - PURPOSE: The purpose of this retrospective study was to identify the
      postoperative complications and disorders associated with open trigger finger
      release. Factors that were investigated by this study included demographic
      details, the number of digits affected, BMI, level of manual strain, trauma,
      received systemic medication, hand dominance, pre-treatment with steroid
      injection, and concomitant diseases. METHODS: One hundred and three patients, who
      underwent open release surgery for 117 trigger fingers and thumbs, were followed
      up until complete resolution of all complaints. Patients' age, BMI, hand
      dominance, occupational manual strain, and previous medical history regarding
      trigger finger or thumb were obtained. Associated conditions and medical
      treatment, trauma, and previous hand surgical interventions were included as
      well. Details regarding duration of complaints, ROM, visual analogue pain scale,
      swelling, recurrence of the disease following previous surgical release, and
      persistence of complaints following corticosteroid injection were examined.
      RESULTS: The dominant hand was not significantly more frequently affected than
      the non-dominant hand. Occupation also did not influence the incidence of trigger
      digit. Patients with systemic steroid therapy had a significantly shorter
      duration of postoperative symptoms with a mean duration of 29.3 days (range, 28
      31 days +/- 1.3). Significantly less postoperative swelling was noticed in
      patients with a pre-surgical steroid injection. The mean duration of symptoms
      before and after surgery was significantly shorter for a trigger thumb than for
      trigger finger. DISCUSSION: Open trigger digit release constitutes an adequate
      low-risk surgical procedure for treatment of trigger digit. In this study, we
      could show that the incidence of this disease is not significantly correlated
      with the manual strain, trauma, BMI, hand dominance or concomitant diseases like
      diabetes mellitus, rheumatoid arthritis, renal insufficiency, and hypothyroidism.
      Additionally, this study illustrates the importance of a careful postoperative
      follow-up treatment to avoid potential persistent functional limitations.

PMID- 22160514
TI  - Prospective evaluation of patients with anterior cruciate ligament reconstruction
      using a patient-based health-related survey: comparison of single-bundle and
      anatomical double-bundle techniques.
AB  - PURPOSE: To compare the treatment outcomes of single-bundle and anatomical double
      bundle anterior cruciate ligament (ACL) reconstructions, we used the patient
      based health-related QOL questionnaire SF-36 to evaluate patients with ACL injury
      who underwent surgical reconstruction using the two techniques. PATIENTS AND
      METHODS: A prospective study was performed on patients who were diagnosed with
      ACL injury and underwent ACL reconstruction. Eighty-four male patients who were
      followed for at least 2 years were analyzed in this study. Forty-four patients
      were operated by single-bundle technique, and 40 by double-bundle technique. SF
      36, Lysholm score, anterior tibial translation, and pivot shift were assessed
      before surgery and 6, 12 and 24 months after surgery. RESULTS: In the
      preoperative SF-36 survey, the scores of almost all the subscales were lower than
      the national standard scores in both groups. After operation, the scores of all
      the subscales improved to the national standard values in all patients, but no
      difference was observed between two groups. Lysholm score, distance of anterior
      tibial translation and pivot shift positive rate improved significantly after
      operation in all patients, but there were no significant differences between two
      groups. DISCUSSION: Although good clinical results have been reported for double
      bundle ACL reconstruction, some studies reported no clear difference compared to
      the conventional single-bundle technique. In the present study, significant
      improvements were achieved after operation in both groups, confirming the
      usefulness of both techniques. No clear merit of one method over the other was
      found, not only from the conventional objective assessments but also from the
      patient-based subjective evaluation.

PMID- 22160515
TI  - Difference in miRNA expression profiles between two cotton cultivars with
      distinct salt sensitivity.
AB  - MicroRNAs (miRNAs) are a class of endogenous, non-coding small RNAs that play
      important roles in many developmental processes and stress responses in plants
      and animals. Cotton (Gossypium hirsutum L.) is considered a relatively salt
      tolerant non-halophytic plant species. To study the role of miRNAs in salt
      adaptation, a salt-tolerant cotton cultivar SN-011 and a salt-sensitive cultivar
      LM-6 were used to detect differentially expressed miRNAs. Using miRNA microarray
      analysis and a computational approach, 17 cotton miRNAs belonging to eight
      families were identified. Although they are conserved, 12 of them showed a
      genotype-specific expression model in both the cultivars. Under salt stress
      treatment, miR156a/d/e, miR169, miR535a/b and miR827b were dramatically down
      regulated in SN-011, while miR167a, miR397a/b and miR399a were up-regulated. Only
      miR159 was found to be down-regulated in LM-6 under salt stress. To gain insight
      into their functional significance, 26 target genes were predicted and their
      functional similarity was further analyzed. Quantitative real-time PCR showed
      that the expression of seven target genes showed a significant inverse
      correlation with corresponding miRNAs. These differentially expressed miRNAs can
      help in further study into the role of transcriptome homeostasis in the
      adaptation responses of cotton to salt.

PMID- 22160516
TI  - The functional SLC11A1 gene polymorphisms are associated with sarcoidosis in
      Turkish population.
AB  - Sarcoidosis (SA) is an immune-mediated multisystemic disorder of unknown etiology
      characterized by the accumulation of lymphocytes, mononuclear phagocytes and
      epithelioid cell granulomas involved in different organs and tissues. The belief
      that genetics contribute to SA etiology is supported by twin studies, disease
      clustering in families and racial differences in incidence rates. Involvements of
      SLC11A1 in macrophage function and activation, makes it an attractive candidate
      gene for immune-mediated and infectious diseases. We investigated the association
      between SA and four polymorphisms of the SLC11A1 gene, including a single
      nucleotide change in intron 4 (INT4); a nonconservative single-base substitution
      at codon 543 (D543N); a TGTG deletion in the 3' untranslated region; and the
      functional (GT)(n) repeat polymorphism in the 5' region, in 95 Turkish SA
      patients and 150 healthy controls, by using amplification refractory mutation
      system-polymerase chain reaction and sequencing. We found significant association
      between SA and INT4 G/C allele frequency (P = 0.0000; odds ratio 2.75; 95%
      confidence interval 1.68-4.52) and 5'(GT)(n) allele 2/3 frequency (P = 0.0000;
      odds ratio 2.69; 95% confidence interval 1.61-4.47) suggesting that SLC11A1 might
      be a plausible candidate gene for SA.

PMID- 22160517
TI  - Identification of a fructose-1,6-bisphosphate aldolase gene and association of
      the single nucleotide polymorphisms with growth traits in the clam Meretrix
      meretrix.
AB  - This study investigated whether there were single nucleotide polymorphisms (SNPs)
      in fructose-1,6-bisphosphate aldolase (FBA) gene associated with growth traits of
      the clam Meretrix meretrix. A FBA gene was identified in M. meretrix and its
      deduced amino acid residues shared high identity with type I aldolase. The FBA
      (MmeFBA) mRNA expression profile was examined by real-time PCR in different
      tissues and the significantly high expression level in foot and adduct muscle
      suggests that MmeFBA is a muscle type aldolase which functions in glycolytic
      pathway. In the MmeFBA gene, we identified four intron SNPs and three exon SNPs
      including a nonsynonymous SNP (mmfbae-2). These SNPs were genotyped in 205 clams
      from two clam populations with significantly different growth performance.
      Results showed that allele frequencies of three SNPs (mmfbai-1, mmfbai-3 and
      mmfbae-2) and the genotype frequency of mmfbai-1 were all significantly different
      between the two populations. The haplotype analysis further supported the three
      SNPs distributed differently between the two populations. This study successively
      characterized three growth-related SNPs in a gene involved in energy metabolism
      of M. meretrix. These findings could contribute the development of phenotype
      selective breeding program in M. meretrix.

PMID- 22160518
TI  - Identification of potential serum biomarkers for Wilms tumor after excluding
      confounding effects of common systemic inflammatory factors.
AB  - Wilms tumor is the most common pediatric tumor of the kidney. Previous studies
      have identified several serum biomarkers for Wilms tumor; however, they lack
      sufficient specificity and may not adequately distinguish Wilms tumor from
      confounding conditions. To date, no specific protein biomarker has been confirmed
      for this pediatric tumor. To identify novel serum biomarkers for Wilms tumor, we
      used proteomic technologies to perform protein profiling of serum samples from
      pre-surgery and post-surgery patients with Wilms tumor and healthy controls. Some
      common systemic inflammatory factors were included to control for systemic
      inflammation. By comparing protein peaks among the three groups of sera, we
      identified two peaks (11,526 and 4,756 Da) showing significant differential
      expression not only between pre-surgery and control sera but also between pre
      surgery and post-surgery sera. These two peaks were identified as serum amyloid
      A1 (SAA1) and apolipoprotein C-III (APO C-III). Western blot analysis confirmed
      that both proteins were expressed at higher levels in pre-surgery sera than in
      post-surgery and control sera. Using the method of leave-1-out for cross
      detection, we demonstrate that detection of these two candidate biomarkers had
      high sensitivity and specificity in discriminating pre-surgery sera from post
      surgery and normal control sera. Taken together, these findings suggest that SAA1
      and APO C-III are two potential biomarkers for Wilms tumor.

PMID- 22160519
TI  - Ethical challenges and interventional pain medicine.

PMID- 22160520
TI  - Computational fluid dynamics of fish gill rakers during crossflow filtration.
AB  - We study crossflow filtration mechanisms in suspension-feeding fishes using
      computational fluid dynamics to model fluid flow and food particle movement in
      the vicinity of the gill rakers. During industrial and biological crossflow
      filtration, particles are retained when they remain suspended in the mainstream
      flow traveling across the filter surface rather than traveling perpendicularly to
      the filter. Here we identify physical parameters and hydrodynamic processes that
      determine food particle movement and retention inside the fish oral cavity. We
      demonstrate how five variables affect flow patterns and particle trajectories:
      (1) flow speed inside the fish oral cavity, (2) incident angle of the flow
      approaching the filter, (3) dimensions of filter structures, (4) particle size,
      and (5) particle density. Our study indicates that empirical experiments are
      needed to quantify flow parameters inside the oral cavity, and morphological
      research is needed to quantify dimensions of the filter apparatus such as gill
      rakers, the gaps between rakers, and downstream barriers. Ecological studies on
      suspension-feeding fishes are also needed to quantify food particle size and
      density, as these variables can affect particle retention due to hydrodynamic
      processes during crossflow filtration.

PMID- 22160521
TI  - Clinical and self breast examination remain important in the era of modern
      screening.
AB  - BACKGROUND: Breast cancer screening recommendations are in flux. We reviewed the
      methods of detecting newly diagnosed breast neoplasms at our institution.
      METHODS: A retrospective review of patients stratified by age was performed to
      compare mammography with self- (SBE) and clinical (CBE) breast examination
      methods of cancer detection from 2005 to 2009. RESULTS: We identified 782
      patients. Patients aged <50 years were more likely to present with palpable
      disease (P < 0.001). Overall, 75% of patients had a mammogram within 24 months.
      There was a higher incidence of Tis tumors and lower incidence of T1 tumors if
      patients had mammography performed within 12 months versus 13-24 months (P <
      0.01); tumor size, hormonal status, and lymph node (LN) status were comparable
      between these two groups. Patients diagnosed by SBE/CBE who had mammography
      performed within 12 months versus 13-24 months did not differ statistically
      according to tumor characteristics. In the screened cohort (mammography within 24
      months), the majority of patients (64%) were diagnosed by mammography. Cancers
      detected by SBE/CBE were larger tumors (2.4 vs. 1.3 cm), higher grade, more
      frequently ER- (29 vs. 16%), triple-negative (21 vs. 10%), and lymph node
      positive (39 vs. 18%; all P <= 0.01). There were no statistically significant
      differences in tumor size, T stage, or hormonal status in patients who had analog
      versus digital mammography. CONCLUSIONS: Whereas the majority of patients had
      image-detected breast cancer, a significant number of image-screened patients
      presented with palpable disease, which were more aggressive cancers. Until
      imaging techniques are refined, SBE and CBE remain important for breast cancer
      diagnosis.

PMID- 22160537
TI  - Plaque-left-behind after brushing: intra-oral reservoir for antibacterial
      toothpaste ingredients.
AB  - OBJECTIVES: Plaque is never fully removed by brushing and may act as a reservoir
      for antibacterial ingredients, contributing to their substantive action. This
      study investigates the contribution of plaque-left-behind and saliva towards
      substantivity of three antibacterial toothpastes versus a control paste without
      antibacterial claims. MATERIALS AND METHODS: First, volunteers brushed 2 weeks
      with a control or antibacterial toothpaste. Next, plaque and saliva samples were
      collected 6 and 12 h after brushing and bacterial concentrations and viabilities
      were measured. The contributions of plaque and saliva towards substantivity were
      determined by combining control plaques with experimental plaque or saliva
      samples and subsequently assessing their viabilities. Bacterial compositions in
      the various plaque and saliva samples were compared using denaturing gradient gel
      electrophoresis. RESULTS: The viabilities of plaques after brushing with Colgate
      Total(r) and Crest-Pro-Health(r) were smaller than of control plaques and up to
      12 h after brushing with Crest-Pro-Health(r) plaques still contained effective,
      residual antibacterial activity against control plaques. No effective, residual
      antibacterial activity could be measured in saliva samples after brushing. There
      was no significant difference in bacterial composition of plaque or saliva after
      brushing with the different toothpastes. CONCLUSIONS: Plaque-left-behind after
      mechanical cleaning contributes to the substantive action of an antibacterial
      toothpaste containing stannous fluoride (Crest-Pro-Health(r)). CLINICAL
      RELEVANCE: The absorptive capacity of plaque-left-behind after brushing is of
      utmost clinical importance, since plaque is predominantly left behind in places
      where its removal and effective killing matter most. Therewith this study
      demonstrates a clear and new beneficial effect of the use of antibacterial
      toothpastes.

PMID- 22160538
TI  - Bleeding incidence after oral surgery with continued oral anticoagulation.
AB  - OBJECTIVES: The aim of this retrospective study was to assess the incidence of
      postoperative hemorrhage in patients treated with coumarins without interruption
      of the anticoagulant treatment undergoing oral surgical procedures, mostly
      osteotomies for tooth removal, when compared with patients who had never been
      anticoagulated. MATERIAL AND METHODS: Six hundred thirty-seven patients underwent
      934 oral surgical procedures on an outpatient basis. The INR was measured
      preoperatively being 2.44 in the mean SD 0.61. Local hemostasis was carried out
      routinely (80%) with collagen fleece, local flap, and acrylic splint. RESULTS: Of
      these 637 patients, 47 presented with a postoperative hemorrhage (7.4%), 15 of
      these 47 cases had to be treated in hospital (2.4%). All patients showed up
      finally with a good wound healing, no administration of blood was necessary, and
      local measures revealed to be sufficient in all cases except for two patients,
      where the preoperative anticoagulant treatment had to be changed for 6 days. The
      bleeding incidence in 285 patients with comparable oral surgical procedures, who
      had never been anticoagulated, was 0.7%. CONCLUSIONS: The results suggest that
      oral surgical procedures can be performed safely without alteration of the oral
      anticoagulant treatment. CINICAL RELEVANCE: Local hemostasis with collagen
      fleece, local flap, and acrylic splint seems to be sufficient to prevent
      postoperative bleeding.

PMID- 22160539
TI  - Identification of cis elements necessary for glucocorticoid induction of growth
      hormone gene expression in chicken embryonic pituitary cells.
AB  - Glucocorticoid (GC) treatment of rat or chicken embryonic pituitary (CEP) cells
      induces premature production of growth hormone (GH). GC induction of the GH gene
      requires ongoing protein synthesis, and the GH genes lack a canonical GC response
      element (GRE). To characterize cis-acting elements and identify trans-acting
      proteins involved in this process, we characterized the regulation of a
      luciferase reporter containing a fragment of the chicken GH gene (-1727/+48) in
      embryonic day 11 CEP cells. Corticosterone (Cort) increased luciferase activity
      and mRNA expression, and mRNA induction was blocked by protein synthesis
      inhibition. Through deletion analysis, we identified a GC-responsive region
      (GCRR) at -1045 to -954. The GCRR includes an ETS-1 binding site and a degenerate
      GRE (dGRE) half site. Nuclear proteins, including ETS-1, bound to a GCRR probe in
      electrophoretic mobility shift assays, and Cort regulated protein binding. Using
      chromatin immunoprecipitation, we found that ETS-1 and GC receptor (GR) were
      associated with the GCRR in CEP cells, and Cort increased GR recruitment to the
      GCRR. Mutation of the ETS-1 site or dGRE site in the -1045/+48 GH reporter
      abolished Cort responsiveness. We conclude that GC regulation of the GH gene
      during development requires cis-acting elements in the GCRR and involves ETS-1
      and GR binding to these elements. Similar ETS-1 elements/dGREs are located in the
      5'-flanking regions of GH genes in mammals, including rodents and humans. This is
      the first study to demonstrate involvement of ETS-1 in GC regulation of the GH
      gene during embryonic development in any species, enhancing our understanding of
      GH regulation in vertebrates.

PMID- 22160540
TI  - Glucose sensing by gut endocrine cells and activation of the vagal afferent
      pathway is impaired in a rodent model of type 2 diabetes mellitus.
AB  - Glucose in the gut lumen activates gut endocrine cells to release 5-HT, glucagon
      like peptide 1/2 (GLP-1/2), and glucose-dependent insulinotropic polypeptide
      (GIP), which act to change gastrointestinal function and regulate postprandial
      plasma glucose. There is evidence that both release and action of incretin
      hormones is reduced in type 2 diabetes (T2D). We measured cellular activation of
      enteroendocrine and enterochromaffin cells, enteric neurons, and vagal afferent
      neurons in response to intestinal glucose in a model of type 2 diabetes mellitus,
      the UCD-T2DM rat. Prediabetic (PD), recent-diabetic (RD, 2 wk postonset), and 3
      mo diabetic (3MD) fasted UCD-T2DM rats were given an orogastric gavage of vehicle
      (water, 0.5 ml /100 g body wt) or glucose (330 MUmol/100 g body wt); after 6 min
      tissue was removed and cellular activation was determined by immunohistochemistry
      for phosphorylated calcium calmodulin-dependent kinase II (pCaMKII). In PD rats,
      pCaMKII immunoreactivity was increased in duodenal 5-HT (P < 0.001), K (P < 0.01)
      and L (P < 0.01) cells in response to glucose; glucose-induced activation of all
      three cell types was significantly reduced in RD and 3MD compared with PD rats.
      Immunoreactivity for GLP-1, but not GIP, was significantly reduced in RD and 3MD
      compared with PD rats (P < 0.01). Administration of glucose significantly
      increased pCaMKII in enteric and vagal afferent neurons in PD rats; glucose
      induced pCaMKII immunoreactivity was attenuated in enteric and vagal afferent
      neurons (P < 0.01, P < 0.001, respectively) in RD and 3MD. These data suggest
      that glucose sensing in enteroendocrine and enterochromaffin cells and activation
      of neural pathways is markedly impaired in UCD-T2DM rats.

PMID- 22160542
TI  - Effects of body temperature maintenance on glucose, insulin, and corticosterone
      responses to acute hypoxia in the neonatal rat.
AB  - One of the biggest challenges of premature birth is acute hypoxia. Hypothermia
      during acute hypoxic periods may be beneficial. We hypothesized that prevention
      of hypothermia during neonatal hypoxia disrupts glucose homeostasis and places
      additional metabolic challenges on the neonate. Pups at PD2 and PD8 were exposed
      to 8% O2 for 3 h, during which they were allowed to either spontaneously cool or
      were kept isothermic. There was also a time control group that was subjected to
      normoxia and kept isothermic. Plasma glucose, insulin, C-peptide, corticosterone,
      and catecholamines were measured from samples collected at baseline, 1 h, 2 h,
      and 3 h. In postnatal day 2 (PD2) rats, hypoxia alone resulted in no change in
      plasma glucose by 1 h, an increase by 2 h, and a subsequent decrease below
      baseline values by 3 h. Hypoxia with isothermia in PD2 rats elicited a large
      increase in plasma insulin at 1 h. In PD8 rats, hypoxia with isothermia resulted
      in an initial increase in plasma glucose, but by 3 h, glucose had decreased
      significantly to below baseline levels. Hypoxia with and without isothermia
      elicited an increase in plasma corticosterone at both ages and an increase in
      plasma epinephrine in PD8 rats. We conclude that the insulin response to hypoxia
      in PD8 rats is associated with an increase in glucose similar to an adult;
      however, insulin responses to hypoxia in PD2 rats were driven by something other
      than glucose. Prevention of hypothermia during hypoxia further disrupts glucose
      homeostasis and increases metabolic challenges.

PMID- 22160541
TI  - Arousal from sleep in response to intermittent hypoxia in rat pups is modulated
      by medullary raphe GABAergic mechanisms.
AB  - Arousal is an important defense against hypoxia during sleep. Rat pups exhibit
      progressive arousal impairment (habituation) with multiple hypoxia exposures. The
      mechanisms are unknown. The medullary raphe (MR) is involved in autonomic
      functions, including sleep, and receives abundant GABAergic inputs. We
      hypothesized that inhibiting MR neurons with muscimol, a GABA(A) receptor
      agonist, or preventing GABA reuptake with nipecotic acid, would impair arousal
      and enhance arousal habituation and that blocking GABA(A) receptors with
      bicuculline would enhance arousal and attenuate habituation. Postnatal day 15
      (P15) to P25 rat pups were briefly anesthetized, and microinjections with aCSF,
      muscimol, bicuculline, or nipecotic acid were made into the MR. After a ~30-min
      recovery, pups were exposed to four 3-min episodes of hypoxia separated by 6 min
      of normoxia. The time to arousal from the onset of hypoxia (latency) was
      determined for each trial. Latency progressively increased across trials
      (habituation) in all groups. The overall latency was greater after muscimol and
      nipecotic acid compared with aCSF, bicuculline, or noninjected controls. Arousal
      habituation was reduced after bicuculline compared with aCSF, muscimol, nipecotic
      acid, or noninjected pups. Increases in latency were mirrored by decreases in
      chamber [O2] and oxyhemoglobin saturation. Heart rate increased during hypoxia
      and was greatest in muscimol-injected pups. Our results indicate that the MR
      plays an important, not previously described, role in arousal and arousal
      habituation during hypoxia and that these phenomena are modulated by GABAergic
      mechanisms. Arousal habituation may contribute to sudden infant death syndrome,
      which is associated with MR serotonergic and GABAergic receptor dysfunction.

PMID- 22160544
TI  - Median preoptic nucleus and subfornical organ drive renal sympathetic nerve
      activity via a glutamatergic mechanism within the paraventricular nucleus.
AB  - The paraventricular nucleus (PVN) of the hypothalamus is involved in the neural
      control of sympathetic drive, but the precise mechanism(s) that influences the
      PVN is not known. The activation of the PVN may be influenced by input from
      higher forebrain areas, such as the median preoptic nucleus (MnPO) and the
      subfornical organ (SFO). We hypothesized that activation of the MnPO or SFO would
      drive the PVN through a glutamatergic pathway. Neuroanatomical connections were
      confirmed by the recovery of a retrograde tracer in the MnPO and SFO that was
      injected bilaterally into the PVN in rats. Microinjection of 200 pmol of N-methyl
      d-aspartate (NMDA) or bicuculline-induced activation of the MnPO and increased
      renal sympathetic activity (RSNA), mean arterial pressure, and heart rate in
      anesthetized rats. These responses were attenuated by prior microinjection of a
      glutamate receptor blocker AP5 (4 nmol) into the PVN (NMDA - DeltaRSNA 72 +/- 8%
      vs. 5 +/- 1%; P < 0.05). Using single-unit extracellular recording, we examined
      the effect of NMDA microinjection (200 pmol) into the MnPO on the firing activity
      of PVN neurons. Of the 11 active neurons in the PVN, 6 neurons were excited by 95
      +/- 17% (P < 0.05), 1 was inhibited by 57%, and 4 did not respond. The increased
      RSNA after activation of the SFO by ANG II (1 nmol) or bicuculline (200 pmol) was
      also reduced by AP5 in the PVN (for ANG II - DeltaRSNA 46 +/- 7% vs. 17 +/- 4%; P
      < 0.05). Prior microinjection of ANG II type 1 receptor blocker losartan (4 nmol)
      into the PVN did not change the response to ANG II or bicuculline microinjection
      into the SFO. The results from this study demonstrate that the sympathoexcitation
      mediated by a glutamatergic mechanism in the PVN is partially driven by the
      activation of the MnPO or SFO.

PMID- 22160543
TI  - Role of omega-hydroxylase in adenosine-mediated aortic response through MAP
      kinase using A2A-receptor knockout mice.
AB  - Previously, we have shown that A(2A) adenosine receptor (A(2A)AR) knockout mice
      (KO) have increased contraction to adenosine. The signaling mechanism(s) for
      A(2A)AR is still not fully understood. In this study, we hypothesize that, in the
      absence of A(2A)AR, omega-hydroxylase (Cyp4a) induces vasoconstriction through
      mitogen-activated protein kinase (MAPK) via upregulation of adenosine A(1)
      receptor (A(1)AR) and protein kinase C (PKC). Organ bath and Western blot
      experiments were done using isolated aorta from A(2A)KO and corresponding wild
      type (WT) mice. Isolated aortic rings from WT and A(2A)KO mice were precontracted
      with submaximal dose of phenylephrine (10(-6) M), and concentration responses for
      selective A(1)AR, A(2A)AR agonists, angiotensin II and cytochrome P-450
      epoxygenase, 20-hydroxyeicosatrienoic acid (20-HETE) PKC, PKC-alpha, and ERK1/2
      inhibitors were obtained. 2-p-(2-Carboxyethyl)-phenethylamino-5'-N
      ethylcarboxamidoadenosine hydrochloride (CGS-21680, A(2A)AR agonist) induced
      concentration-dependent relaxation in WT, which was blocked by methylsulfonyl
      propargyloxyphenylhexanamide (cytochrome P-450-epoxygenase inhibitor; 10(-5) M)
      and also with removal of endothelium. A(1) agonist, 2-chloro-N(6)
      cyclopentyladenosine (CCPA) produced higher contraction in A(2A)KO aorta than WT
      (49.2 +/- 8.5 vs. 27 +/- 5.9% at 10(-6) M, P < 0.05). 20-HETE produced higher
      contraction in A(2A)KO than WT (50.6 +/- 8.8 vs. 21.1 +/- 3.3% at 10(-7) M, P <
      0.05). Contraction to CCPA in WT and A(2A)KO aorta was inhibited by PD-98059
      (p42/p44 MAPK inhibitor; 10(-6) M), chelerythrine chloride (nonselective PKC
      blocker; 10(-6) M), Go-6976 (selective PKC-alpha inhibitor; 10(-7) M), and
      HET0016 (20-HETE inhibitor; 10(-5) M). Also, contraction to 20-HETE in WT and
      A(2A)KO aorta was inhibited by PD-98059 and Go-6976. Western blot analysis
      indicated the upregulation of A(1)AR, Cyp4a, PKC-alpha, and phosphorylated-ERK1/2
      in A(2A)KO compared with WT (P < 0.05), while expression of Cyp2c29 was
      significantly higher in WT. CCPA (10(-6) M) increased the protein expression of
      PKC-alpha and phosphorylated-ERK1/2, while HET0016 significantly reduced the CCPA
      induced increase in expression of these proteins. These data suggest that, in the
      absence of A(2A)AR, Cyp4a induces vasoconstriction through MAPK via upregulation
      of A(1)AR and PKC-alpha.

PMID- 22160545
TI  - Measuring mitochondrial respiration in intact single muscle fibers.
AB  - Measurement of mitochondrial function in skeletal muscle is a vital tool for
      understanding regulation of cellular bioenergetics. Currently, a number of
      different experimental approaches are employed to quantify mitochondrial
      function, with each involving either mechanically or chemically induced
      disruption of cellular membranes. Here, we describe a novel approach that allows
      for the quantification of substrate-induced mitochondria-driven oxygen
      consumption in intact single skeletal muscle fibers isolated from adult mice.
      Specifically, we isolated intact muscle fibers from the flexor digitorum brevis
      muscle and placed the fibers in culture conditions overnight. We then quantified
      oxygen consumption rates using a highly sensitive microplate format. Peak oxygen
      consumption rates were significantly increased by 3.4-fold and 2.9-fold by
      simultaneous stimulation with the uncoupling agent, carbonyl cyanide p
      (trifluoromethoxy)phenylhydrazone (FCCP), and/or pyruvate or palmitate exposure,
      respectively. However, when calculating the total oxygen consumed over the entire
      treatment, palmitate exposure resulted in significantly more oxygen consumption
      compared with pyruvate. Further, as proof of principle for the procedure, we
      isolated fibers from the mdx mouse model, which has known mitochondrial deficits.
      We found significant reductions in initial and peak oxygen consumption of 51% and
      61% compared with fibers isolated from the wild-type (WT) animals, respectively.
      In addition, we determined that fibers isolated from mdx mice exhibited less
      total oxygen consumption in response to the FCCP + pyruvate stimulation compared
      with the WT mice. This novel approach allows the user to make mitochondria
      specific measures in a nondisrupted muscle fiber that has been isolated from a
      whole muscle.

PMID- 22160546
TI  - Calcium influx determines the muscular response to electrotransfer.
AB  - Cell membrane permeabilization by electric pulses (electropermeabilization),
      results in free exchange of ions across the cell membrane. The role of
      electrotransfer-mediated Ca(2+)-influx on muscle signaling pathways involved in
      degeneration (beta-actin and MurF), inflammation (IL-6 and TNF-alpha), and
      regeneration (MyoD1, myogenin, and Myf5) was investigated, using pulse parameters
      of both electrochemotherapy (8 HV) and DNA delivery (HVLV). Three pulsing
      conditions were used: 8 high-voltage pulses (8 HV), resulting in large
      permeabilization and ion flux, and a combination of one high-voltage pulse and
      one low-voltage pulse (HVLV), either alone or in combination with injection of
      DNA. Mice and rats were anesthetized before pulsing. At the times given, animals
      were killed, and intact tibialis cranialis muscles were excised for analysis.
      Uptake of Ca(2+) was assessed using (45)Ca as a tracer. Using gene expression
      analyses and histology, we showed a clear association between Ca(2+) influx and
      muscular response. Moderate Ca(2+) influx induced by HVLV pulses results in
      activation of pathways involved in immediate repair and hypertrophy. This
      response could be attenuated by intramuscular injection of EGTA reducing Ca(2+)
      influx. Larger Ca(2+) influx as induced by 8-HV pulses leads to muscle damage and
      muscle fiber regeneration through recruitment of satellite cells. The extent of
      Ca(2+) influx determines the muscular response to electrotransfer and, thus, the
      success of a given application. In the case of electrochemotherapy, in which the
      objective is cell death, a large influx of Ca(2+) may be beneficial, whereas for
      DNA electrotransfer, muscle recovery should occur without myofiber loss to ensure
      preservation of plasmid DNA.

PMID- 22160547
TI  - Assessing the body image: relevance, application and instruments for oncological
      settings.
AB  - PURPOSE: Body image is the sum of physical, cognitive, emotional, and relational
      elements that, when integrated, allow the development of a whole, healthy self
      identity. Even though body image is normally studied in relation to eating
      disorders, it can also be influenced by other pathologies, including cancer. In
      oncology, an effective body image assessment is fundamental. The physical effects
      of cancer and cancer treatments are important and frequently irreversible also on
      a functional and emotional level; however, only few surveys have investigated
      body image in this peculiar context. METHODS: An extensive literature review was
      carried out in PubMed and PsycINFO. We considered articles published from 1990 to
      2010. RESULTS: Two hundred sixty-three papers matched the search criteria.
      Assessment methodologies included clinical interviews, self-report measures,
      questionnaires, symptom check lists, and graphic tests and projective techniques.
      After excluding the instruments that referred to eating disorders, validated only
      for adolescents, and/or projective and graphic tests, we found 81 articles with
      six questionnaires specifically dedicated to body image assessment in oncology.
      CONCLUSIONS: From our systematic review, we could identify six instruments
      specifically designed for assessing body image in the oncological area. In this
      paper, we discuss their general characteristics, psychometrics properties and the
      clinical implications, and body image relevance on the quality of life in cancer
      patients.

PMID- 22160549
TI  - Incidence of propofol injection pain and effect of lidocaine pretreatment during
      upper gastrointestinal endoscopy.
AB  - BACKGROUND/AIMS: Propofol has been used in the past for sedation in upper
      gastrointestinal (GI) endoscopic procedures. This study aimed to measure the
      incidence of propofol injection pain and evaluate the effect of lidocaine on pain
      caused during sedative upper GI endoscopic examinations. METHODS: Subjects
      scheduled to undergo sedative diagnostic upper GI endoscopy were randomly
      assigned to lidocaine and placebo groups. Pretreatment with a bolus of 1%
      lidocaine 2 ml or normal saline 2 ml into the largest dorsal vein of the non
      dominant hand was followed by propofol administration. Pain intensity was
      estimated by an examiner blinded to the group assignment using a four-point
      verbal rating scale. A score of 1-3 was regarded as pain. RESULTS: A total of 121
      patients (males, 69; age, 58.6 +/- 12.1 years) completed the study; 61 and 60
      subjects were randomly assigned to the lidocaine and placebo groups,
      respectively. The incidence of pain during upper GI endoscopy was 60%. The
      lidocaine group showed a lower incidence of pain than the placebo group (37.7%
      vs. 60.0%, P = 0.018). The lidocaine group perceived significantly less pain than
      the placebo group (median pain score, 0 vs. 1, P = 0.008). Only lidocaine
      pretreatment was an independently associated factor against pain perception (OR,
      0.380; 95% CI, 0.177-0.815; P = 0.013). CONCLUSIONS: Pretreatment using lidocaine
      was found to be effective in reducing propofol injection-induced pain. However,
      its usefulness for GI endoscopic procedures in daily clinical practice needs
      further evaluation because of the low intensity of pain.

PMID- 22160550
TI  - Neuropsychology, neuroimaging or motor phenotype in diagnosis of Parkinson's
      disease-dementia: which matters most?
AB  - Parkinson's disease (PD) is a neurodegenerative disorder affecting not only the
      motor system but also the cognitive and behavioral domains. Although there are
      many studies addressing the issue of cognition, a universally recognized method
      to diagnose patients with dementia is still lacking. The aim of this study was to
      determine which neuropsychological test is the most reliable in the diagnosis of
      dementia in PD and to establish if mini mental state examination (MMSE) is enough
      to detect this condition. We studied 200 consecutive PD patients through an
      extensive neuropsychological battery, clinical evaluation and brain magnetic
      resonance imaging over a period of 4 years. A logistic regression model was used
      to evaluate the interplay between possible risk factors and the accuracy of
      different neuropsychological tests. PD patients with dementia performed
      significantly worse in all the tests as compared to patients with PD alone:
      phonological verbal fluency, attentional matrices, Rey auditory verbal learning
      test and digit span were the most useful tools. Age and disease duration were
      correlated with cognitive impairment. No relevant differences were detected in
      phenotype, affected body side at onset, levodopa equivalent daily dose or
      neuroimaging findings (except for the occurrence of atrophy). Despite reasonable
      accuracy of MMSE (90%), its positive predictive value is only 74%. Using at least
      3 neuropsychological tests, among those more significant detected with logistic
      regression analysis, the positive predictive value rises to 91%. In conclusion,
      the use of an extensive neuropsychological battery is still recommended in the
      diagnosis of dementia in PD.

PMID- 22160551
TI  - Imipramine reverses depressive-like parameters in pneumococcal meningitis
      survivor rats.
AB  - Pneumococcal meningitis is a severe infectious disease of the central nervous
      system, associated with acute inflammation and might cause damage to the host,
      such as deafness, blindness, seizure, and learning deficits. However, infectious
      diseases can play a significant role in the etiology of neuropsychiatric
      disturbances. In this context, we evaluated depressive-like parameters;
      corticosterone and ACTH levels in pneumococcal meningitis surviving rats. Wistar
      rats underwent a magna cistern tap receiving either 10 MUL sterile saline or a
      Streptococcus pneumoniae suspension at the concentration of 5 * 10(9) cfu/mL.
      After 3 days of meningitis induction procedure, the animals were treated with
      imipramine at 10 mg/kg or saline for 14 days (3rd-17th day). The consumption of
      sweet food was measured for 7 days (10th-17th day). The meningitis group
      decreased the sucrose intake and increased the levels of corticosterone and ACTH
      levels in the serum and TNF-alpha in the cortex; however, the treatment with
      imipramine reverted the reduction of sweet food consumption, normalized hormonal
      levels and TNF-alpha in the cortex. Our results supported the hypothesis that the
      pneumococcal meningitis surviving rats showed depressive-like behavior and
      alterations in the hypothalamus-pituitary-adrenal axis.

PMID- 22160553
TI  - Can we really do computer-aided drug design?
AB  - In this article, we discuss what we mean by 'design' and contrast this with the
      application of computational methods in drug discovery. We suggest that the
      predictivity of the computational models currently applied in drug discovery is
      not yet sufficient to permit a true design paradigm, as demonstrated by the large
      number of compounds that must currently be synthesised and tested to identify a
      successful drug. However, despite the uncertainties in predictions, computational
      methods have enormous potential value in narrowing the range of compounds to
      consider, by eliminating those that have negligible chance of being a successful
      drug, while focussing efforts on chemistries with the best likelihood of success.
      Applied appropriately, computational approaches can support decision-makers in
      achieving multi-parameter optimisation to guide the selection and design of
      compounds with the best chance of achieving an appropriate balance of properties
      for a drug discovery project's objectives. Finally, we consider some approaches
      that may contribute over the next 25 years to improve the accuracy and
      transferability of computational models in drug discovery and move towards a
      genuine design process.

PMID- 22160552
TI  - Multifunctional acyltransferases from Tetrahymena thermophila.
AB  - Multifunctional acyltransferases are able to catalyze the esterification of
      various acyl-acceptors with activated fatty acids. Here we describe the
      identification of four proteins from Tetrahymena thermophila that share certain
      properties with mammalian acyltransferases regarding their predicted
      transmembrane structure, their molecular mass and the typical acyltransferase
      motif. Expression of the Tetrahymena sequences results in production of
      triacylglycerols and wax esters in recombinant yeast when appropriate substrates
      are provided. The in vitro characterization shows, that these enzymes are capable
      of esterifying different acyl-acceptors including fatty alcohols, diols,
      diacylglycerols and isoprenols with acyl-CoA thioesters. Based on these catalytic
      activities and the sequence similarities of the Tetrahymena proteins with acyl
      CoA:diacylglycerol acyltransferase 2 (DGAT2) family members, we conclude that we
      identified a new group of DGAT2-related multifunctional acyltransferases from
      protozoan organisms.

PMID- 22160554
TI  - The perspectives of computational chemistry modeling.
AB  - The on-line tools for computational chemistry modeling will be increasingly used
      in the future. This will bring the advantages both for the authors and the
      readers.

PMID- 22160555
TI  - Computation, experiment and molecular design.

PMID- 22160556
TI  - A very short history of structure-based design: how did we get here and where do
      we need to go?

PMID- 22160557
TI  - Rebuilding my fortress.

PMID- 22160558
TI  - When work, family and friendship collide.
AB  - Mandi's sister was diagnosed with breast cancer and was referred to our Familial
      Cancer Program. The young age of diagnosis, characteristics of the cancer and
      family history suggested genetic testing and Helen was the genetic counselor
      involved throughout the testing process. In relaying this personal and
      professional story we have tried to describe the issues we faced and how we
      negotiated some of the difficulties when the boundaries between our many roles of
      family member, friends, colleagues and professionals became blurred.

PMID- 22160559
TI  - The incentive.

PMID- 22160560
TI  - Salvage chemotherapy for recurrent or persistent clear cell carcinoma of the
      ovary: a single-institution experience for a series of 20 patients.
AB  - BACKGROUND: Recurrent or persistent clear cell carcinoma (CCC) of the ovary is
      particularly chemotherapy resistant. The purpose of this study was to review our
      extensive institutional experiences with recurrent or persistent CCC with the aim
      of finding a more effective chemotherapy regimen. METHODS: The medical records of
      67 patients treated for CCC of the ovary were retrospectively reviewed to select
      patients subsequently treated for recurrence or persistence of the disease.
      RESULTS: The review identified 20 patients treated for recurrent or persistent
      CCC. For these 20 patients, 9 chemotherapeutic regimens, with 125 cycles, were
      administered. Gemcitabine monotherapy showed the best response rate [1 partial
      response (20%) and 2 stable diseases out of 5 patients so treated]. A partial
      response was observed with a combination of docetaxel plus irinotecan in 1 of 11
      patients (9%). Stable disease was observed in 1 of 9 cases on a
      paclitaxel/carboplatin doublet and in 1 case on a docetaxel/carboplatin doublet.
      The median overall survival time was 8 months (range, 2-52). One group of
      patients who received gemcitabine therapy showed significantly better survival (n
      = 5, median 18 months) compared with a group who did not (n = 15, median 7
      months) (P = 0.0108, by univariate analysis). In addition, multivariate Cox
      proportional hazards analysis revealed that gemcitabine administration was a
      significant factor for survival (hazard ratio: 13.0, 95% CI: 1.4727-115.2255, P =
      0.02). CONCLUSION: Although most chemotherapeutic regimens for recurrent or
      persistent CCC have little or no effect, gemcitabine showed modest activity and
      is the most effective agent we have tested to date.

PMID- 22160561
TI  - Glial reactivity in dogs with visceral leishmaniasis: correlation with T
      lymphocyte infiltration and with cerebrospinal fluid anti-Leishmania antibody
      titres.
AB  - Visceral leishmaniasis is a multisystemic zoonotic disease that can manifest with
      several symptoms, including neurological disorders. Because glial cells are
      extensively associated with the immune response within the brain, we evaluated
      the morphology of astrocytes and microglia of dogs naturally infected with
      Leishmania chagasi. We used immunohistochemical and lectin-histochemical
      techniques for morphological analyses and we also examined the glial correlation
      with lymphocyte infiltration of the brain and with the presence of anti
      Leishmania antibodies within the cerebrospinal fluid of the dogs. Although we did
      not detect a shared morphological pattern in the astrocytes or microglia in the
      brain tissue, these cells were more intensely labelled in infected dogs than in
      the control group. The density of microglia was increased in the
      ependymal/subependymal area, thus demonstrating a strong correlation with the
      presence of T lymphocytes and with cerebrospinal fluid antibody titres. Thus, our
      results indicate a pro-inflammatory state in the brains of dogs naturally
      infected with L. chagasi and strongly suggest that microglia and astrocytes are
      involved in the pathogenesis of the neurological disorders of visceral
      leishmaniasis in dogs.

PMID- 22160562
TI  - Genetic and phenotypic parameter estimates for reproduction traits in indigenous
      Arsi-Bale goats.
AB  - The study was conducted to evaluate reproductive performances and estimate
      genetic parameters for reproduction traits in Arsi-Bale goats. A total of 792
      kidding records collected from 2001 to 2007 were used. Parity of dam, year,
      season and type of kidding were investigated as fixed effects by PROC GLM of SAS.
      Derivative-Free Restricted Maximum Likelihood (DFREML) method was used to
      estimate genetic parameters by fitting four animal models. Parity of dam and year
      of kidding influenced (P < 0.05) all the traits. The overall means for age at
      first kidding (AFK), kidding interval (KI), litter size at birth (LSB), litter
      size at weaning (LSW), litter weight at birth (LWB), litter weight at weaning
      (LWW), abortion and dystocia were 574.9 +/- 8.3 days, 280.0 +/- 13.7 days, 1.6 +/
      0.03, 1.37 +/- 0.03, 3.7 +/- 0.08 kg, 9.11 +/- 0.38 kg, 3.8% and 0.13%,
      respectively. The estimates of direct additive heritability for the traits,
      except for abortion and dystocia, under the best model (direct animal for AFK and
      repeatability model for other traits) were 0.245 +/- 0.19, 0.060 +/- 0.08, 0.074
      +/- 0.05, 0.006 +/- 0.05, 0.125 +/- 0.05, 0.053 +/- 0.07, respectively, while the
      corresponding permanent environmental effects were 0.00 +/- 0.00, 0.07 +/- 0.07,
      0.08 +/- 0.05, 0.172 +/- 0.06, 0.03 +/- 0.04 and 0.07 +/- 0.05, respectively.
      Repeatability estimates for KI, LSB, LSW, LWB and LWW were 0.13, 0.15, 0.18, 0.16
      and 0.12, respectively. Genetic correlations between reproductive traits vary
      from medium to high. Arsi-Bale goats have good reproductive performance with low
      incidence of reproductive disorder. Except for AFK, other traits have low
      estimates of heritabilities with high genetic correlation among the traits.
      Repeated measures of the traits are needed before deciding to keep or cull the
      animal.

PMID- 22160563
TI  - Massive choroidal effusion and painful secondary glaucoma from underlying uveal
      melanoma.

PMID- 22160564
TI  - Cysteine-rich 61 (CYR61) is up-regulated in proliferative diabetic retinopathy.
AB  - BACKGROUND: To investigate the role of CYR61 as a retinal angiogenic factor in
      proliferative diabetic retinopathy (PDR). METHODS: Effects of CYR61 on RF/6A cell
      proliferation, migration and angiogenesis were observed by MTT assay, Transwell
      assay, and tube formation assay. The expression and distribution of CYR61 on
      retina layers of diabetic mouse were demonstrated by immunohistochemistry. The
      expression of Cyr61 mRNA in diabetic mouse retina was evaluated by reverse
      transcription-polymerase chain reaction (RT-PCR). Vitreous CYR61 levels of PDR
      and non-diabetic patients were measured by enzyme-linked immunosorbent assay
      (ELISA). Expression and distribution of CYR61 on epiretinal membrane of PDR,
      proliferative vitreoretinopathy (PVR) and idiopathic epiretinal membrane were
      evaluated by immunohistochemistry. RESULTS: RF/6A cell proliferation, migration
      and tube formation capacity increased with increased concentration of CYR61 (p =
      0.000). Anti-CYR61 antibody could inhibit cell migration and tube formation
      promoted by CYR61. In diabetic mouse, CYR61 was expressed in retina layers just
      as normal mouse, but the staining was stronger than normal in ganglion cell layer
      and inner plexiform layer. The Cyr61 mRNA expression in retina of diabetic mouse
      was more than that in normal mouse (p = 0.009). Vitreous CYR61 level was higher
      in patients with PDR than non-diabetic patients (p = 0.000). PDR patients with
      plenty of neovasculature on retina and epiretinal membranes had higher level of
      vitreous CYR61 than patients with little neovasculature (p = 0.001). CYR61
      expressed in the cytoplasm of epiretinal membranes in PDR, especially in the wall
      cells of the tube-like structure. CONCLUSIONS: CYR61 are likely to be involved in
      the pathogenesis of diabetic retinopathy, and may play a role in the course of
      neovasculation.

PMID- 22160565
TI  - Urologists' and GPs' knowledge of hereditary prostate cancer is suboptimal for
      prostate cancer counseling: a nation-wide survey in The Netherlands.
AB  - A family history of prostate cancer (PCa) is an established risk factor for PCa.
      In case of a positive family history, the balance between positive and adverse
      effects of prostate-specific antigen (PSA) testing might be different from the
      general population, for which the European Randomized Study of Screening for
      Prostate Cancer (ERSPC) showed a beneficial effect on mortality. This, however,
      went at the cost of considerable overtreatment. This study assessed Dutch
      physicians' knowledge of heredity and PCa and their 'post-ERSPC' attitude towards
      PCa testing, including consideration of family history. In January 2010, all
      Dutch urologists and clinical geneticists (CGs) and 300 general practitioners
      (GPs) were invited by email to complete an anonymous online survey, which
      contained questions about hereditary PCa and their attitudes towards PCa case
      finding and screening. 109 urologists (31%), 69 GPs (23%) and 46 CGs (31%)
      completed the survey. CGs had the most accurate knowledge of hereditary PCa. All
      but 1 CG mentioned at least one inherited trait with PCa, compared to only 25% of
      urologists and 9% of GPs. CGs hardly ever counseled men about PCa testing. Most
      urologists and GPs discuss possible risks and benefits before testing for PCa
      with PSA. Remarkably, 35-40% of them do not take family history into
      consideration. Knowledge of urologists and GPs about heredity and PCa is
      suboptimal. Hence, PCa counseling might not be optimal for men with a positive
      family history. Multidisciplinary guidelines on this topic should be developed to
      optimize personalized counseling.

PMID- 22160566
TI  - Direct targets of the tomato-ripening regulator RIN identified by transcriptome
      and chromatin immunoprecipitation analyses.
AB  - The physiological and biochemical changes in fruit ripening produce key
      attributes of fruit quality including color, taste, aroma and texture. These
      changes are driven by the highly regulated and synchronized activation of a huge
      number of ripening-associated genes. In tomato (Solanum lycopersicum), a typical
      climacteric fruit, the MADS-box transcription factor RIN is one of the earliest
      acting ripening regulators, required for both ethylene-dependent and ethylene
      independent pathways. Although we previously identified several direct RIN
      targets, many additional targets remain unidentified, likely including key
      ripening-associated genes. Here, we report the identification of novel RIN
      targets by transcriptome and chromatin immunoprecipitation (ChIP) analyses.
      Transcriptome comparisons by microarray of wild-type and rin mutant tomatoes
      identified 342 positively regulated genes and 473 negatively regulated genes by
      RIN during ripening. Most of the positively regulated genes contained possible
      RIN-binding (CArG-box) sequences in their promoters. Subsequently, we selected
      six genes from the positively regulated genes and a ripening regulator gene, CNR,
      and assayed their promoters by quantitative ChIP-PCR to examine RIN binding. All
      of the seven genes, which are involved in cell wall modification, aroma and
      flavor development, pathogen defense and transcriptional regulation during
      ripening, are targets of RIN, suggesting that RIN may control multiple diverse
      ripening processes. In particular, RIN directly regulates the expression of the
      ripening-associated transcription factors, CNR, TDR4 and a GRAS family gene,
      providing an important clue to elucidate the complicated transcriptional cascade
      for fruit ripening.

PMID- 22160567
TI  - GsZFP1, a new Cys2/His2-type zinc-finger protein, is a positive regulator of
      plant tolerance to cold and drought stress.
AB  - Plant acclimation to environmental stress is controlled by a complex network of
      regulatory genes that compose distinct stress-response regulons. The C2H2-type
      zinc-finger proteins (ZFPs) have been implicated in different cellular processes
      involved in plant development and stress responses. Through microarray analysis,
      an alkaline (NaHCO(3))-responsive ZFP gene GsZFP1 was identified and subsequently
      cloned from Glyycine soja. GsZFP1 encodes a 35.14 kDa protein with one C2H2-type
      zinc-finger motif. The QALGGH domain, conserved in most plant C2H2-type ZFPs, is
      absent in the GsZFP1 protein sequence. A subcellular localization study using a
      GFP fusion protein indicated that GsZFP1 is localized to the nucleus. Real-time
      RT-PCR analysis showed that GsZFP1 was induced in the leaf by ABA (100 MUM), salt
      (200 mM NaCl), and cold (4 degrees C), and in the root by ABA (100 MUM), cold (4
      degrees C), and drought (30% PEG 6000). Over-expression of GsZFP1 in transgenic
      Arabidopsis resulted in a greater tolerance to cold and drought stress, a
      decreased water loss rate, and an increase in proline irrespective of
      environmental conditions. The over-expression of GsZFP1 also increased the
      expression of a number of stress-response marker genes, including CBF1, CBF2,
      CBF3, NCED3, COR47, and RD29A in response to cold stress and RAB18, NCED3, P5CS,
      RD22, and RD29A in response to drought stress, especially early during stress
      treatments. Our studies suggest that GsZFP1 plays a crucial role in the plant
      response to cold and drought stress.

PMID- 22160568
TI  - Drug-induced lupus anticoagulants and antiphospholipid antibodies.
AB  - Lupus anticoagulants (LA) are immunoglobulins (IgG, IgM, and/or IgA) which
      interfere with one or more of phospholipid-dependent in vitro coagulation tests,
      eg, activated partial thromboplastin time (aPTT), kaolin clotting time (KCT),
      dilute Russell viper venom time (dRVVT), and dilute prothrombin time (dPT). LAs
      may be seen in a variety of clinical settings including the primary
      antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE), other
      autoimmune diseases, secondary to infections, malignancies, and in association
      with certain drugs. LAs associated with the antiphospholipid syndrome and other
      autoimmune disease recognize certain phospholipid-binding proteins (beta(2)
      glycoprotein I [beta(2)GPI] or prothrombin). Many drugs have been implicated as
      possibly causing LAs, although the majority of such cases are limited to a select
      few. Drug-induced LAs are heterogeneous, differing in laboratory findings as well
      as related clinical complications. This paper reviews the English medical
      literature on drug-induced LA and potential mechanisms of induction.

PMID- 22160569
TI  - The interaction of blood proteins with brucine.
AB  - The features of brucine (BC) binding to two blood proteins, bovine hemoglobin
      (BHb), and bovine serum albumin (BSA), were investigated via fluorescence,
      circular dichroism and UV/Vis absorption spectroscopy. The results revealed that
      BC caused the fluorescence quenching of blood proteins by the formation of BC
      protein complex. The corresponding thermodynamic parameters were measured at
      different temperatures. The process of binding BC molecule on protein was a
      spontaneous molecular interaction procedure in which entropy increased and Gibbs
      free energy decreased. Hydrophobic and electrostatic interactions play a major
      role in stabilizing the complex. The molecular docking has been employed to
      explore the binding site of the BC in BHb and BSA on the Autodock 4.2. The
      distances r between BC and protein were calculated to be 4.93 and 5.08 nm for
      BHb, and BSA, respectively. The effect of BC on the conformation of blood
      proteins was analyzed using CD, synchronous fluorescence and three-dimensional
      fluorescence spectra.

PMID- 22160571
TI  - Inositol phosphate kinase Vip1p interacts with histone chaperone Asf1p in
      Saccharomyces cerevisiae.
AB  - Histone eviction and deposition are critical steps in many nuclear processes. The
      histone H3/H4 chaperone Asf1p is highly conserved and is involved in DNA
      replication, DNA repair, and transcription. To identify the factors concerned
      with anti-silencing function 1 (ASF1), we purified Asf1p-associated factors from
      the yeast Saccharomyces cerevisiae by a GST pull-down experiment, and mass
      spectrometry analysis was performed. Several factors are specifically associated
      with Asf1p, including Vip1p. VIP1 is conserved from yeast to humans and encodes
      inositol hexakisphoshate and inositol heptakisphosphate kinase. Vip1p interacted
      with Asf1p as a dimer or in a complex with another protein(s). Deletion of VIP1
      did not affect the interaction between Asf1p and other Asf1p-associated factors.
      An in vitro GST pull-down assay indicated a direct interaction between Asf1p and
      Vip1p, and the interaction between the two factors in vivo was detected by an
      immunoprecipitation experiment. Furthermore, genetic experiments revealed that
      VIP1 disruption increased sensitivity to 6-azauracil (6-AU), but not to DNA
      damaging reagents in wild-type and ASF1-deleted strains. It is thought that 6-AU
      decreases nucleotide levels and reduces transcription elongation. These
      observations suggest that the association of Asf1p and Vip1p may be implicated in
      transcription elongation.

PMID- 22160570
TI  - Synergistic inhibitory effects by the combination of gefitinib and genistein on
      NSCLC with acquired drug-resistance in vitro and in vivo.
AB  - In clinical practice, most patients with non small cell lung cancer (NSCLC) who
      respond to tyrosine kinase inhibitors eventually progress because of an acquired
      resistance mutation, T790M, in epidermal growth factor receptor (EGFR). Thus, it
      is important to identify a new drug to reduce resistance. The aim of this study
      was to test whether genistein combined with gefitinib is effective against NSCLC
      in a cell line carrying T790M, and to clarify the underlying mechanisms. The
      human lung cancer cell line H1975 was used as an in vitro and in vivo model.
      Cells were treated with gefitinib, genistein, or a combination at a range of
      concentrations. Cell proliferation was calculated to assess the anticancer
      effects of the compounds in vitro. Flow cytometry and Western blotting were
      employed to determine the inhibitory effects on proliferation and the induction
      of apoptosis. The in vivo effects of the compounds were examined using a
      xenografted nude mouse model for validation. Gefitinib together with genistein
      enhanced both growth inhibition and apoptosis; however, the greatest synergistic
      effect was observed at low concentrations. p-EGFR, p-Akt, and p-mTOR expressions
      in vitro were reduced more by the combined use of the drugs, whereas caspase-3
      and PARP activities were increased. Significantly more tumor growth inhibition
      was detected following combination treatment in the in vivo model. These findings
      suggest that genistein enhanced the antitumor effects of gefitinib in a NSCLC
      cell line carrying the T790M mutation. This synergistic activity may be due to
      increased inhibition of the downstream molecular and pro-apoptotic effects of
      EGFR.

PMID- 22160572
TI  - Glutathione S-transferase M1 and T1 gene polymorphism and COPD risk in smokers:
      an updated analysis.
AB  - We evaluated the association between GSTM1 and GSTT1 gene polymorphisms and
      susceptibility to chronic obstructive pulmonary disease (COPD) in smokers. A meta
      analysis of the published case-control studies was performed. Published
      literature was retrieved from PubMed, EMBASE, and China National Knowledge
      Infrastructure (CNKI), with last update in February, 2011. Data were extracted
      and a fixed- or random-effects model was used to calculate pooled odds ratios
      with 95% confidence intervals depending on statistical heterogeneity. Fourteen
      eligible studies, comprising 1,665 COPD cases and 1,614 controls, were included
      in the meta-analysis. The combined analyses showed that there was a significant
      difference in GSTM1 genotype distribution between COPD cases and controls among
      Caucasians, but not among Asians. The combined GSTM1/GSTT1 null genotype
      conferred a 1.36-fold greater risk for COPD in Asian smokers. The GSTT1 null
      genotype alone was not associated with enhanced risk for COPD. The GSTM1 null
      genotype is significantly associated with an increasing susceptibility to COPD in
      Caucasian smokers, but not in Asian smokers. The GSTM1/GSTT1 null genotype is a
      significant risk factor for developing COPD in Asian smokers. The GSTT1 null
      genotype, however, was not associated with COPD.

PMID- 22160573
TI  - Interaction of human serum albumin with 10-hydroxycamptothecin: spectroscopic and
      molecular modeling studies.
AB  - In this work, fluorescence spectroscopy in combination with circular dichroism
      spectroscopy and molecular modeling was employed to investigate the binding of 10
      hydroxycamptothecin (HCPT) to human serum albumin (HSA) under simulative
      physiological conditions. The experiment results showed that the fluorescence
      quenching of HSA by HCPT was a result of the formation of HCPT-HSA complex. The
      corresponding association constants (K (a)) between HCPT and HSA at four
      different temperatures were determined according to the modified Stern-Volmer
      equation. The results of thermodynamic parameters DeltaG, DeltaH, and DeltaS
      indicated that hydrogen bonds and van der Waals forces played major roles for
      HCPT-HSA association. Site marker competitive displacement experiment indicated
      that the binding of HCPT to HSA primarily took place in sub-domain IIA (site I).
      Molecular docking study further confirmed the binding mode and the binding site
      obtained by fluorescence and site marker competitive experiments. The
      conformational investigation showed that the presence of HCPT decreased the alpha
      helical content of HSA and induced the slight unfolding of the polypeptides of
      protein, which confirmed some micro-environmental and conformational changes of
      HSA molecules.

PMID- 22160574
TI  - Lack of association between MDR1 C3435T polymorphism and chemotherapy response in
      advanced breast cancer patients: evidence from current studies.
AB  - The transmembrane transport of anticancer drugs is mainly regulated by P
      glycoprotein encoded by the human multidrug resistance gene 1 gene (MDR1). Since
      there were controversies regarding the association between MDR1 C3435T
      polymorphism and response to chemotherapy among patients with advanced breast
      cancer, a meta-analysis of the link was conducted. A total of 7 studies consist
      of 464 advanced breast cancer patients relating MDR1 C3435T polymorphism to the
      response of chemotherapy were included in this meta-analysis. The main analysis
      revealed a lack of association between the MDR1 C3435T and response to
      chemotherapy, with odds ratios (ORs) and their corresponding 95% confidence
      intervals (CIs) of 1.37 (95% CI: 0.78-2.40), 1.17 (95% CI: 0.69-2.01), 1.18 (95%
      CI: 0.76-1.84) and 1.61 (95% CI: 0.70-3.68) for homozygous comparison,
      heterozygous comparison, dominant model and recessive model, respectively. The
      subgroup analysis by ethnicity did not change the pattern of results, with ORs of
      0.99 (95% CI: 0.11-9.07), 0.68 (95% CI: 0.29-1.60), 0.81 (95% CI: 0.36-1.85) and
      1.51 (95% CI: 0.77-2.96), in homozygous comparison, heterozygous comparison,
      dominant model and recessive model, respectively in Caucasian, and 1.50 (95% CI:
      0.75-3.03), 1.72 (95% CI: 0.85-3.47), 1.59 (95% CI: 0.90-2.80) and 2.29 (95% CI:
      0.51-10.35), respectively in Asian. The available evidence indicates that MDR1
      C3435T polymorphism cannot be considered as a reliable predictor of response to
      chemotherapy in patients with advanced breast cancer.

PMID- 22160575
TI  - Expression analysis and functional characterization of a novel cold-responsive
      gene CbCOR15a from Capsella bursa-pastoris.
AB  - The cold-responsive (COR) genes involved in C-repeat binding factor signaling
      pathway function essentially in cold acclimation of higher plants. A novel COR
      gene CbCOR15a from shepherd's purse (Capsella bursa-pastoris) was predicted to be
      a homolog of COR15 in Arabidopsis. The analysis of tissue specific expression
      pattern as well as characterization of the CbCOR15a promoter revealed that the
      expression of CbCOR15a was induced by coldness not only in leaves and stem but
      also in roots. Sequence analysis showed that a 909 bp promoter region of CbCOR15a
      contained two CRT/DRE elements, two ABRE elements, one auxin-responsive TGA
      element and one MeJA-responsive CGTCA-motif. In young seedlings the expression of
      CbCOR15a could be apparently increased by SA, ABA, MeJA and IAA, and transiently
      increased by GA(3) accompanied by obvious feedback suppression. According to the
      altered physiological index values in tobacco under cold treatments, the
      overexpression of CbCOR15a significantly increased the cold tolerance of
      transgenic tobacco plants. It can be suggested that CbCOR15a was involved in cold
      response of Capsella bursa-pastoris associated with SA, ABA, MeJA, IAA and GA(3)
      regulation and confers enhanced cold acclimation in transgenic plants.

PMID- 22160576
TI  - Meta-analysis of association between cytokine gene polymorphisms and lung cancer
      risk.
AB  - The aim of this study was to evaluate the association between various cytokine
      gene polymorphisms and lung cancer (LC) susceptibility. We searched Pubmed,
      Elsevier Science Direct, China National Knowledge Infrastructure database,
      Chinese Biomedical database, Google scholar. Totally, 20 studies involving 6,467
      cases and 8,320 controls were included in the meta-analysis. The effects of eight
      polymorphisms, i.e. TNF-alpha 308G/A, IL-6 174G/C, IL-1beta 31T/C, IL-1beta
      511C/T, COX-2 8473T/C, IL-10 1082G/A, IL-10 819C/T, and IL-10 592C/A were
      evaluated. The combined odds ratio (OR) with 95% confidence interval (95% CI) was
      calculated to estimate the strength of the association in a fixed or random
      effect model. Heterogeneity and publication bias were also assessed. We found a
      significant association between IL-10 polymorphism and LC. For IL-10 1082G/A, the
      overall ORs (95% CI) of the G versus A, GG versus AA, and GG/GA versus AA were
      2.35 (1.16-4.76), 2.07 (1.16-3.70) and 3.17 (1.31-7.68), respectively. For IL-10
      819C/T, the pooled ORs (95% CI) of the C versus T and CC versus TT were 1.27
      (1.01-1.58) and 2.27 (1.32-3.89). For IL-10 592C/A, the comparison of subjects in
      the CC or CC/CA genotype versus AA homozygotes showed significant results (OR =
      2.00, 95% CI: 1.24-3.23; OR = 1.80, 95% CI: 1.28-2.54). But, other gene
      polymorphisms did not reach statistical associations. IL-10 1082G/A, 819C/T and
      592C/A polymorphisms might be risk factors for LC. TNF-alpha 308G/A, IL-6 174G/C,
      IL-1beta 31T/C, IL-1beta 511C/T, COX-2 8473T/C polymorphisms were not detected to
      be related to the risk for LC. Due to the limitation of the number of the
      studies, we should take the conclusion with caution. While, further studies are
      necessary for more precise association.

PMID- 22160577
TI  - The current status of alternatives to animal testing and predictive toxicology
      methods using liver microfluidic biochips.
AB  - In this paper, we will consider new in vitro cell culture platforms and the
      progress made, based on the microfluidic liver biochips dedicated to
      pharmacological and toxicological studies. Particular emphasis will be given to
      recent developments in the microfluidic tools dedicated to cell culture (more
      particularly liver cell culture), in silico opportunities for Physiologically
      Based PharmacoKinetic (PBPK) modelling, the challenge of the mechanistic
      interpretations offered by the approaches resulting from "multi-omics" data
      (transcriptomics, proteomics, metabolomics, cytomics) and imaging microfluidic
      platforms. Finally, we will discuss the critical features regarding
      microfabrication, design and materials, and cell functionality as the key points
      for the future development of new microfluidic liver biochips.

PMID- 22160578
TI  - Decomposition and description of the nasal cavity form.
AB  - Patient-specific studies of physiological flows rely on anatomically realistic or
      idealized models. Objective comparison of datasets or the relation of specific to
      idealized geometries has largely been performed in an ad hoc manner. Here, two
      rational procedures (based respectively on Fourier descriptors and medial axis
      (MA) transforms) are presented; each provides a compact representation of a
      complex anatomical region, specifically the nasal airways. The techniques are
      extended to furnish average geometries. These retain a sensible anatomical form,
      facilitating the identification of a specific anatomy as a set of weighted
      perturbations about the average. Both representations enable a rapid translation
      of the surface description into a virtual model for computation of airflow,
      enabling future work to comprehensively investigate the relation between anatomic
      form and flow-associated function, for the airways or for other complex
      biological conduits. The methodology based on MA transforms is shown to allow
      flexible geometric modeling, as illustrated by a local alteration in airway
      patency. Computational simulations of steady inspiratory flow are used to explore
      the relation between the flow in individual vs. averaged anatomical geometries.
      Results show characteristic flow measures of the averaged geometries to be within
      the range obtained from the original three subjects, irrespective of averaging
      procedure. However the effective regularization of anatomic form resulting from
      the shape averaging was found to significantly reduce trans-nasal pressure loss
      and the mean shear stress in the cavity. It is suggested that this may have
      implications in attempts to relate model geometries and flow patterns that are
      broadly representative.

PMID- 22160579
TI  - Development and characterization of phyto-vesicles of beta-sitosterol for the
      treatment of androgenetic alopecia.
AB  - Alopecia is a psychologically distressing phenomenon. Androgenetic alopecia (AGA)
      is the most common form of alopecia, which affects millions of men and women
      worldwide, and is an androgen driven disorder. To study the effect of beta
      sitosterol phyto-vesicles on AGA, the testosterone-induced alopecia model was
      used. For the study, the albino rats were used and the period of study was 21
      days. beta-Sitosterol is a phytosterol which is chemically similar to
      cholesterol. This compound was found suitable for the preparation of phyto
      vesicles by the process involving its complexation with phosphatidyl choline.
      Pharmacokinetic studies of beta-sitosterol reveal its poor absorption through the
      intestine. The objective of the present study is to enhance the bioavailability
      of beta-sitosterol by its complexation with phosphatidyl choline and then to
      formulate it as phyto-vesicles for the treatment of alopecia. The complex of beta
      sitosterol was prepared with phosphatidyl choline and characterized on the basis
      of solubility, melting point, TLC, UV, IR and NMR spectroscopy. This complex was
      then formulated as phyto-vesicles and then characterized. The results revealed
      that effect on alopecia is better in case of phyto-vesicles as compared to the
      complex, physical mixture and the beta-sitosterol itself. Enhanced
      bioavailability of the beta-sitosterol complex may be due to the amphiphilic
      nature of the complex, which greatly enhance the water and lipid solubility of
      the compound. The present study clearly indicates the superiority of phyto
      vesicles over the complex and beta-sitosterol, in terms of better absorption and
      improved activity for the treatment of alopecia.

PMID- 22160580
TI  - Spin electron paramagnetic resonance of albumin for diagnosis of oral squamous
      cell carcinoma (OSCC).
AB  - OBJECTIVES: Albumin has a known capability to modulate free serum concentrations
      of proteins produced by tumour cells. The technique of spin probe labelling of
      albumin followed by electron paramagnetic resonance (EPR) spectroscopy may allow
      identification of these structural and functional changes, which regularly occur
      as consequence of binding tumour metabolites as ligands. The aim of the present
      study was a proof of principle evaluation of EPR-analysis of peripheral blood
      samples as possible predictor for oral squamous cell carcinoma (OSCC). MATERIAL
      AND METHODS: The present study is designed as gender-matched cohort. EPR was
      tested after retrieval of peripheral blood samples. The study group is
      represented by 32 patients with OSCC, and the control group consisted of 30
      healthy patients. RESULTS: Overall analysis exhibited a diagnostic sensitivity of
      72% (23/32 OSCC group) and a specificity of 80% (24/30 control group). Subgroup
      analysis revealed ten patients with elevated leukocytes (>10,000/MUl; n = 9 [OSCC
      group] and n = 1 [control group]). After exclusion of patients with elevated
      white blood cell count, sensitivity considerably increased to 87% and specificity
      to 83%. CONCLUSION: EPR analysis of peripheral blood samples might be appropriate
      to support the clinician in primary and follow-up diagnosis of potential tumours
      such as OSCC. Unfortunately, subgroup analysis characterises the method
      vulnerable to inflammation. CLINICAL RELEVANCE: Nevertheless, our preliminary
      results are intriguing, as diagnosis of OSCC appears possible by simple
      peripheral blood examination. Thus, further appraisal of this novel method with
      inclusion of different tumour entities, systemic conditions and inflammation in a
      larger study population appears highly valuable.

PMID- 22160581
TI  - Mindfulness and problem gambling: a review of the literature.
AB  - This article reviews the literature with respect to mindfulness and its potential
      for reducing the severity of problem gambling behaviour. Interest in the role of
      mindfulness as a treatment for problem gambling has gained the attention of
      researchers across Australia, the United States, and Canada. However, the
      literature is limited and current studies have severe methodological limitations.
      Despite this issue, investigations have revealed that dispositional mindfulness
      is related to less severe problem gambling outcomes and that psychological
      distress, overconfidence and risk willingness, myopic focus on reward and ego
      involvement may act as mediators in this relationship. Moreover, the literature
      indicates that the inverse relationship between dispositional mindfulness and
      psychological distress may be mediated by factors such as values clarification;
      emotional, cognitive, and behavioural flexibility; non-attachment; emotion
      dysregulation/distress intolerance; thought suppression; and rumination. This
      article discusses the theoretical and clinical implications of these
      relationships with respect to mindfulness-based interventions for problem
      gambling. It is recommended that the approach be considered with cautious
      optimism.

PMID- 22160582
TI  - Health-related quality of life in high-grade glioma patients: a prospective
      single-center study.
AB  - PURPOSE: In this single center study, we aimed to assess quality of life and
      cognitive and emotional distress in patients treated for high-grade glioma.
      METHODS AND MATERIALS: A hundred and eighteen patients with high-grade glioma
      were prospectively enrolled. We assessed HRQoL at baseline (after surgery before
      radiotherapy), at the end of radiotherapy and during follow-up (every 3 months
      for the first 2 years and every 6 months between 2 and 5 years) using the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire 30 (EORTC-C30), Brain Cancer Module-20 (BN-20), Minimental State
      Examination (MMSE) and Hospital Anxiety and Depression Scale (HADS). Baseline
      scores, and first 18-month follow-up period scores were included to statistical
      analysis. RESULTS: Sixty-five (55%) patients had progressive tumor. Global score,
      physical, role and emotional function, insomnia (p for each <0.001) and appetite
      loss (p: 0.008) scores of EORTC-C30 significantly related to disease progression.
      According to BN-20 seizure and leg weakness (p < 0.001), drowsiness and bladder
      control (p: 0.002), motor dysfunction (p: 0.001), future uncertainty (p: 0.04),
      visual disorder (p: 0.008) and communication deficit (p: 0.006) symptoms
      significantly related to disease progression. There were significant decrements
      in orientation, attention and calculation and language scores (p values were
      0.017, 0.005 and 0.003, respectively) of MMSE. The baseline and follow-up anxiety
      and depression scores did not differ significantly. CONCLUSION: We conclude that
      there were many changes in patients with high-grade glioma during the course of
      the disease and most of them were related to disease progression.

PMID- 22160585
TI  - Phylogenetic and serological analysis of turnip ringspot virus and radish mosaic
      virus isolates.
AB  - Turnip ringspot virus (TuRSV) has been proposed to be a member of a new species
      in the genus Comovirus. Its remarkable host-range similarity to radish mosaic
      virus (RaMV) may have led to its misrecognition in the past. Findings from both
      sequence analysis and serological tests support the assignment of TuRSV to a new
      comovirus species. In addition, phylogenetic analysis suggests that the two
      genome segments of some TuRSV isolates have a heterogeneous origin.

PMID- 22160584
TI  - Involvement of liver X receptor alpha in histone modifications across the target
      fatty acid synthase gene.
AB  - The liver X receptor alpha (LXRalpha), a member of the nuclear receptor
      superfamily, has been shown to regulate the expression of the fatty acid synthase
      (FAS) gene through direct interaction with the FAS promoter. However, its
      regulation of gene expression is not completely understood. Histone modifications
      and chromatin remodeling are closely linked to transcriptional activation of
      genes. In the present study, we examined the effect of LXRalpha activation or
      silencing on histone modifications (i.e., acetylation, methylation, and
      phosphorylation) across the FAS gene, with the aim to investigate whether
      LXRalpha could regulate its target gene expression at the epigenetic level. The
      addition of LXR agonist T0901317 or ectopic expression of LXRalpha stimulated the
      FAS transcription, which was coupled with increased levels of histones H3 and H4
      acetylation and H3 phosphorylation and methylation at the LXR response element
      (LXRE). LXR ligation or overexpression induced distinct histone modification
      patterns at the distal region 2,272 bp upstream from the transcription start site
      (TSS) and TSS of the FAS gene. Moreover, RNA interference-mediated downregulation
      of LXRalpha impaired the histone acetylation and methylation but not
      phosphorylation on the FAS gene. In conclusion, we provide evidence that LXRalpha
      ligation-mediated transcriptional activation of the FAS gene is associated with
      LXRalpha-dependent histone acetylation and methylation rather than
      phosphorylation on this target gene.

PMID- 22160586
TI  - Computational chemistry and cheminformatics: an essay on the future.
AB  - Computers have changed the way we do science. Surrounded by a sea of data and
      with phenomenal computing capacity, the methodology and approach to scientific
      problems is evolving into a partnership between experiment, theory and data
      analysis. Given the pace of change of the last twenty-five years, it seems folly
      to speculate on the future, but along with unpredictable leaps of progress there
      will be a continuous evolution of capability, which points to opportunities and
      improvements that will certainly appear as our discipline matures.

PMID- 22160587
TI  - Some thoughts on the "A" in computer-aided molecular design.

PMID- 22160588
TI  - Computational chemistry in 25 years.
AB  - Here we are making some predictions based on three methods: a straightforward
      extrapolations of the existing trends; a self-fulfilling prophecy; and picking
      some current grievances and predicting that they will be addressed or solved. We
      predict the growth of multicore computing and dramatic growth of data, as well as
      the improvements in force fields and sampling methods. We also predict that
      effects of therapeutic and environmental molecules on human body, as well as
      complex natural chemical signalling will be understood in terms of three
      dimensional models of their binding to specific pockets.

PMID- 22160589
TI  - Characterization of Prototheca zopfii associated with outbreak of bovine clinical
      mastitis in herd of Beijing, China.
AB  - Prototheca zopfii (P. zopfii) has become an important cause of bovine mastitis in
      many countries. In the present study, to better understand the occurrence of one
      clinical mastitis (CM) outbreak due to P. zopfii, the molecular characterization
      and resistance patterns of the microalga were described. P. zopfii strains were
      isolated from 17 of 23 quarters, which suffered CM in the outbreak, and 7 of 46
      CM recovered quarters before the outbreak, as well as 2 of 75 environmental
      samples in the dairy farm. All strains were identified as genotype 2 by genotype
      specific PCR analysis. Results of in vitro antimicrobial and antifungal
      susceptibility tests indicated that these strains were resistant to majority of
      tested drugs, with the only exception of amphotericin B, nystatin, streptomycin,
      gentamicin, and amikacin. This is the first report about CM outbreak caused by P.
      zopfii in China. These data suggest that P. zopfii may represent a serious risk
      in the studied herd, and this microalga could be an important potential pathogen
      causing mastitis in dairy herds of Beijing.

PMID- 22160590
TI  - Protein kinase Calpha inhibitor enhances the sensitivity of human pancreatic
      cancer HPAC cells to Clostridium perfringens enterotoxin via claudin-4.
AB  - Protein kinase C (PKC) is overexpressed in cancer, including pancreatic cancer,
      compared with normal tissue. Moreover, PKCalpha is considered one of the
      biomarkers for the diagnosis of cancers. In several human cancers, the claudin
      tight junction molecules are abnormally regulated and are thus promising
      molecular targets for diagnosis and therapy with Clostridium perfringens
      enterotoxin (CPE). In order to investigate the changes of tight junction
      functions of claudins via PKCalpha activation in pancreatic cancer cells, the
      well-differentiated human pancreatic cancer cell line HPAC, with its highly
      expressed tight junction molecules and well-developed barrier function, was
      treated with the PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA).
      Treatment with TPA modified the activity of phosphoPKCalpha and caused an
      increase of the Snail family members Snail, Slug and Smad-interacting protein 1
      and a decrease of E-cadherin. In HPAC cells treated with TPA, downregulation of
      claudin-1 and mislocalization of claudin-4 and occludin around the nuclei were
      observed, together with a decrease in the numbers of tight junction strands and
      an increase in phosphorylation of claudin-4. The barrier function and the
      cytotoxicity of CPE were significantly decreased on TPA treatment. All such
      changes after TPA treatment were prevented by inhibitors of panPKC and PKCalpha.
      These findings suggest that, in human pancreatic cancer cells, PKCalpha
      activation downregulates tight junction functions as a barrier and as a receptor
      of CPE via the modification of claudin-1 and -4 during epithelial to mesenchymal
      transition-like changes. PKCalpha inhibitors might represent potential
      therapeutic agents against human pancreatic cancer cells by use of CPE
      cytotoxicity via claudin-4.

PMID- 22160591
TI  - A genetic risk predictor for breast cancer using a combination of low-penetrance
      polymorphisms in a Japanese population.
AB  - Genome-wide association studies (GWASs) have identified genetic variants
      associated with breast cancer. Most GWASs to date have been conducted in women of
      European descent, however, and the contribution of these variants as predictors
      in Japanese women is unknown. Here, we analyzed 23 genetic variants identified in
      previous GWASs and conducted a case-control study with 697 case subjects and
      1,394 age- and menopausal status-matched controls. We fit conditional regression
      models with genetic variants and conventional risk factors. In addition, we
      created a polygenetic risk score, using those variants with a statistically
      significant association with breast cancer risk, and also evaluated the
      contribution of these genetic predictors using the c statistic. Eleven single
      nucleotide polymorphisms (SNPs) revealed significant associations with breast
      cancer risk. A dose-dependent association was observed between the risk of breast
      cancer and the genetic risk score, which was an aggregate measure of alleles in
      seven selected variants, namely FGFR2-rs2981579, TOX3/TNRC9-rs3803662, C6orf97
      rs2046210, 8q24-rs13281615, SLC4A7-rs4973768, LSP1-rs38137198, and CASP8
      rs10931936. Compared to women with scores of 3 or less, odds ratios (ORs) for
      women with scores of 4-5, 6-7, 8-9, and 10 or more were 1.33 (95% confidence
      interval, 1.00-1.80), 1.71 (1.26-2.30), 3.01 (1.97-4.58), and 8.69 (2.75-27.5),
      respectively (P (trend) = 1.9 * 10(-9)). The c statistic for a model including
      the genetic risk score in addition to the conventional risk factors was 0.6933,
      versus 0.6652 with the conventional risk factors only (P = 1.3 * 10(-4)).
      Population-attributable fraction of the risk score was 33.0%. In conclusion, we
      identified a genetic risk predictor of breast cancer in a Japanese population.
      Risk models which include a genetic risk score are possibly useful in
      distinguishing women at high risk of breast cancer from those at low risk,
      particularly in the context of targeted prevention.

PMID- 22160592
TI  - Super-sticky familial infections caused by Panton-Valentine leukocidin-positive
      ST22 community-acquired methicillin-resistant Staphylococcus aureus in Japan.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), which
      often produces Panton-Valentine leukocidin (PVL), is an emerging threat in the
      community. In Japan, for example, PVL-positive ST8 CA-MRSA (USA 300), which
      originated from the United States, persisted in families for a year and caused
      severe invasive infection in a child. In this study, we describe a long-term
      familial infection cluster caused by novel PVL-positive CA-MRSA, which most
      probably originated from India. This MRSA persisted in related families for more
      than 2 years with colonization of, for example, the nares and cheek. At least 6
      of 12 members (50%) developed deep cutaneous abscesses, including recurrent and
      multifocal abscesses, every 1.2 months on average. All MRSA isolates from
      colonization and abscesses were the same, albeit with a variant in pulsed-field
      gel electrophoresis analysis. The MRSA exhibited the genotype
      ST22/spa113(t005)/SCCmecIVa/coagulase gene (coa) novel type and strong hemolysis
      activity. Moreover, the MRSA exhibited high biofilm formation (which was markedly
      enhanced by sub-MICs of oxacillin). Some patients were treated with levofloxacin,
      with successful MRSA eradication even from the whole body surface sites; however,
      short-term patient follow-up was not sufficient to demonstrate eradication of the
      familial infection cluster. The data suggest that PVL-positive novel ST22 CA-MRSA
      emerged in Japan, causing a long-term familial infection cluster, and that the
      success of ST22 CA-MRSA as both a colonizer and a pathogen could result from the
      combination of its strong biofilm formation and other virulence factors. A long
      term patient (or carrier) follow-up is needed in the community.

PMID- 22160593
TI  - Promiscuous targeting of polytopic membrane proteins to SecYEG or YidC by the
      Escherichia coli signal recognition particle.
AB  - Protein insertion into the bacterial inner membrane is facilitated by SecYEG or
      YidC. Although SecYEG most likely constitutes the major integration site, small
      membrane proteins have been shown to integrate via YidC. We show that YidC can
      also integrate multispanning membrane proteins such as mannitol permease or TatC,
      which had been considered to be exclusively integrated by SecYEG. Only SecA
      dependent multispanning membrane proteins strictly require SecYEG for
      integration, which suggests that SecA can only interact with the SecYEG
      translocon, but not with the YidC insertase. Targeting of multispanning membrane
      proteins to YidC is mediated by signal recognition particle (SRP), and we show by
      site-directed cross-linking that the C-terminus of YidC is in contact with SRP,
      the SRP receptor, and ribosomal proteins. These findings indicate that SRP
      recognizes membrane proteins independent of the downstream integration site and
      that many membrane proteins can probably use either SecYEG or YidC for
      integration. Because protein synthesis is much slower than protein transport, the
      use of YidC as an additional integration site for multispanning membrane proteins
      may prevent a situation in which the majority of SecYEG complexes are occupied by
      translating ribosomes during cotranslational insertion, impeding the
      translocation of secretory proteins.

PMID- 22160594
TI  - Epidermal growth factor induction of front-rear polarity and migration in
      keratinocytes is mediated by integrin-linked kinase and ELMO2.
AB  - Epidermal growth factor (EGF) is a potent chemotactic and mitogenic factor for
      epidermal keratinocytes, and these properties are central for normal epidermal
      regeneration after injury. The involvement of mitogen-activated protein kinases
      as mediators of the proliferative effects of EGF is well established. However,
      the molecular mechanisms that mediate motogenic responses to this growth factor
      are not clearly understood. An obligatory step for forward cell migration is the
      development of front-rear polarity and formation of lamellipodia at the leading
      edge. We show that stimulation of epidermal keratinocytes with EGF, but not with
      other growth factors, induces development of front-rear polarity and directional
      migration through a pathway that requires integrin-linked kinase (ILK),
      Engulfment and Cell Motility-2 (ELMO2), integrin beta1, and Rac1. Furthermore,
      EGF induction of front-rear polarity and chemotaxis require the tyrosine kinase
      activity of the EGF receptor and are mediated by complexes containing active
      RhoG, ELMO2, and ILK. Our findings reveal a novel link between EGF receptor
      stimulation, ILK-containing complexes, and activation of small Rho GTPases
      necessary for acquisition of front-rear polarity and forward movement.

PMID- 22160595
TI  - Calpains promote alpha2beta1 integrin turnover in nonrecycling integrin pathway.
AB  - Collagen receptor integrins recycle between the plasma membrane and endosomes and
      facilitate formation and turnover of focal adhesions. In contrast, clustering of
      alpha2beta1 integrin with antibodies or the human pathogen echovirus 1 (EV1)
      causes redistribution of alpha2 integrin to perinuclear multivesicular bodies,
      alpha2-MVBs. We show here that the internalized clustered alpha2 integrin remains
      in alpha2-MVBs and is not recycled back to the plasma membrane. Instead, receptor
      clustering and internalization lead to an accelerated down-regulation of
      alpha2beta1 integrin compared to the slow turnover of unclustered alpha2
      integrin. EV1 infection or integrin degradation is not associated with
      proteasomal or autophagosomal processes and shows no significant association with
      lysosomal pathway. In contrast, degradation is dependent on calpains, such that
      it is blocked by calpain inhibitors. We show that active calpain is present in
      alpha2-MVBs, internalized clustered alpha2beta1 integrin coprecipitates with
      calpain-1, and calpain enzymes can degrade alpha2beta1 integrin. In conclusion,
      we identified a novel virus- and clustering-specific pathway that diverts
      alpha2beta1 integrin from its normal endo/exocytic traffic to a nonrecycling,
      calpain-dependent degradative endosomal route.

PMID- 22160597
TI  - Three-dimensional ultrastructure of the septin filament network in Saccharomyces
      cerevisiae.
AB  - Septins are conserved GTP-binding proteins involved in membrane
      compartmentalization and remodeling. In budding yeast, five mitotic septins
      localize at the bud neck, where the plasma membrane is enriched in
      phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P(2)). We previously established
      the subunit organization within purified yeast septin complexes and how these
      hetero-octamers polymerize into filaments in solution and on PtdIns4,5P(2)
      containing lipid monolayers. How septin ultrastructure in vitro relates to the
      septin-containing filaments observed at the neck in fixed cells by thin-section
      electron microscopy was unclear. A morphological description of these filaments
      in the crowded space of the cell is challenging, given their small cross section.
      To examine septin organization in situ, sections of dividing yeast cells were
      analyzed by electron tomography of freeze-substituted cells, as well as by cryo
      electron tomography. We found networks of filaments both perpendicular and
      parallel to the mother-bud axis that resemble septin arrays on lipid monolayers,
      displaying a repeat pattern that mirrors the molecular dimensions of the
      corresponding septin preparations in vitro. Thus these in situ structures most
      likely represent septin filaments. In viable mutants lacking a single septin, in
      situ filaments are still present, although more disordered, consistent with other
      evidence that the in vivo function of septins requires filament formation.

PMID- 22160596
TI  - Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is
      accompanied by a nutritional stress response involving Atf1p and Pcr1p that is
      suppressible by Xpo-t/Los1p.
AB  - Deletion of the sla1(+) gene, which encodes a homologue of the human RNA-binding
      protein La in Schizosaccharomyces pombe, causes irregularities in tRNA
      processing, with altered distribution of pre-tRNA intermediates. We show, using
      mRNA profiling, that cells lacking sla1(+) have increased mRNAs from amino acid
      metabolism (AAM) genes and, furthermore, exhibit slow growth in Edinburgh minimal
      medium. A subset of these AAM genes is under control of the AP-1-like, stress
      responsive transcription factors Atf1p and Pcr1p. Although S. pombe growth is
      resistant to rapamycin, sla1-Delta cells are sensitive, consistent with
      deficiency of leucine uptake, hypersensitivity to NH4, and genetic links to the
      target of rapamycin (TOR) pathway. Considering that perturbed intranuclear pre
      tRNA metabolism and apparent deficiency in tRNA nuclear export in sla1-Delta
      cells may trigger the AAM response, we show that modest overexpression of S.
      pombe los1(+) (also known as Xpo-t), encoding the nuclear exportin for tRNA,
      suppresses the reduction in pre-tRNA levels, AAM gene up-regulation, and slow
      growth of sla1-Delta cells. The conclusion that emerges is that sla1(+) regulates
      AAM mRNA production in S. pombe through its effects on nuclear tRNA processing
      and probably nuclear export. Finally, the results are discussed in the context of
      stress response programs in Saccharomyces cerevisiae.

PMID- 22160598
TI  - Yeast formin Bni1p has multiple localization regions that function in polarized
      growth and spindle orientation.
AB  - Formins are conserved proteins that assemble unbranched actin filaments in a
      regulated, localized manner. Budding yeast's two formins, Bni1p and Bnr1p,
      assemble actin cables necessary for polarized cell growth and organelle
      segregation. Here we define four regions in Bni1p that contribute to its
      localization to the bud and at the bud neck. The first (residues 1-333) requires
      dimerization for its localization and encompasses the Rho-binding domain. The
      second (residues 334-821) covers the Diaphanous inhibitory-dimerization-coiled
      coil domains, and the third is the Spa2p-binding domain. The fourth region
      encompasses the formin homology 1-formin homology 2-COOH region of the protein.
      These four regions can each localize to the bud cortex and bud neck at the right
      stage of the cell cycle independent of both F-actin and endogenous Bni1p. The
      first three regions contribute cumulatively to the proper localization of Bni1p,
      as revealed by the effects of progressive loss of these regions on the actin
      cytoskeleton and fidelity of spindle orientation. The fourth region contributes
      to the localization of Bni1p in tiny budded cells. Expression of mislocalized
      Bni1p constructs has a dominant-negative effect on both growth and nuclear
      segregation due to mislocalized actin assembly. These results define an
      unexpected complexity in the mechanism of formin localization and function.

PMID- 22160599
TI  - The phosphoinositide-associated protein Rush hour regulates endosomal trafficking
      in Drosophila.
AB  - Endocytosis regulates multiple cellular processes, including the protein
      composition of the plasma membrane, intercellular signaling, and cell polarity.
      We have identified the highly conserved protein Rush hour (Rush) and show that it
      participates in the regulation of endocytosis. Rush localizes to endosomes via
      direct binding of its FYVE (Fab1p, YOTB, Vac1p, EEA1) domain to
      phosphatidylinositol 3-phosphate. Rush also directly binds to Rab GDP
      dissociation inhibitor (Gdi), which is involved in the activation of Rab
      proteins. Homozygous rush mutant flies are viable but show genetic interactions
      with mutations in Gdi, Rab5, hrs, and carnation, the fly homologue of Vps33.
      Overexpression of Rush disrupts progression of endocytosed cargo and increases
      late endosome size. Lysosomal marker staining is decreased in Rush-overexpressing
      cells, pointing to a defect in the transition between late endosomes and
      lysosomes. Rush also causes formation of endosome clusters, possibly by affecting
      fusion of endosomes via an interaction with the class C Vps/homotypic fusion and
      vacuole protein-sorting (HOPS) complex. These results indicate that Rush controls
      trafficking from early to late endosomes and from late endosomes to lysosomes by
      modulating the activity of Rab proteins.

PMID- 22160600
TI  - Fibroblast morphology on dynamic softening of hydrogels.
AB  - Despite cellular environments having dynamic characteristics, many laboratories
      utilized static polyacrylamide hydrogels to study the ECM-cell relationship. To
      attain a more in vivo like environment, we have developed a dynamic, DNA
      crosslinked hydrogel (DNA gel). Through the controlled delivery of DNA, we can
      temporally decrease or increase gel stiffness while expanding or contracting the
      gel, respectively. These dual mechanical changes make DNA gels a cell-ECM model
      for studying dynamic mechano-regulated processes, such as wound healing. Here, we
      characterized DNA gels on a mechanical and cellular level. In contrast to our
      previous publication, in which we examined the increasing stiffness effects on
      fibroblast morphology, we examined the effects of decreased matrix stiffness on
      fibroblast morphology. In addition, we quantified the bulk and/or local stress
      and strain properties of dynamic gels. Gels generated about 0.5 Pa stress and
      about 6-11% strain upon softening to generate larger and more circular
      fibroblasts. These results complemented our previous study, where dynamic gels
      contracted upon stiffening to generate smaller and longer fibroblasts. In
      conclusion, we developed a biomaterial that increases and decreases in stiffness
      while contracting and expanding, respectively. We found that the dynamic
      deformation directionality of the matrix determined the fibroblast morphology and
      possibly influences function.

PMID- 22160601
TI  - "The Proceedings of the Collaborative Group of the Americas on Inherited
      Colorectal Cancer" Delta Centre-Ville Hotel, Montreal, Quebec, Canada, October 10
      11, 2011. Abstracts.

PMID- 22160602
TI  - Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO
      and BOADICEA in a population-based series of 183 German families.
AB  - Many studies have evaluated the performance of risk assessment models for BRCA1/2
      mutation carrier probabilities in different populations, but to our knowledge
      very few studies have been conducted in the German population so far. In the
      recent study, we validated the performance of three risk calculation models by
      names BRCAPRO, Myriad and BOADICEA in 183 German families who had undergone
      molecular testing of mutations in BRCA1 and BRCA2 with an indication based on
      clinical criteria regarding their family history of cancer. The sensitivity and
      specificity at the conventional threshold of 10% as well as for a threshold of
      20% were evaluated. The ability to discriminate between carriers and non-carriers
      was judged by the area under the receiver operating characteristics curve. We
      further focused on the performance characteristic of these models in patients
      carrying large genomic rearrangements as a subtype of mutations which is
      currently gaining increasing importance. BRCAPRO and BOADICEA performed almost
      equally well in our patient population, but we found a lack of agreement to
      Myriad. The results obtained from this study were consistent with previously
      published results from other population and racial/ethnic groups. We suggest
      using model specific decision thresholds instead of the recommended universal
      value of 10%. We further suggest integrating the CaGene5 software package, which
      includes BRCAPRO and Myriad, in the genetic counselling of German families with
      suspected inherited breast and ovarian cancer because of the good performance of
      BRCAPRO and the substantial ease of use of this software.

PMID- 22160603
TI  - Evaluation and management of small renal masses: looking beyond the tumor margin.
AB  - In an effort to preserve renal function, nephron-sparing approaches such as
      partial nephrectomy are now routinely performed for the treatment of small renal
      masses (SRMs). To date, several groups have studied the utility of examining the
      renal parenchyma contained beyond the tumor margin of partial nephrectomy
      specimens for histopathologic evidence of non-neoplastic disease processes. The
      diagnosis of progressive renal disease through the study of this tissue allows
      for early medical intervention with possible further preservation of renal
      function. In this review, we discuss the management of SRMs with an emphasis on
      the emerging role of evaluating tumor specimens for non-neoplastic pathologic
      abnormalities. We believe that the thorough study of tissue contained beyond the
      tumor margin of partial nephrectomy specimens is the next step in preserving
      renal function and improving survival for patients with SRMs.

PMID- 22160605
TI  - Intake, digestibility, performance, and carcass traits of beef cattle of
      different gender.
AB  - The performance, intake, feed efficiency, and carcass traits of beef cattle from
      different gender profile were assessed. Fifteen animals (five steers, five spayed
      heifers, and five intact heifers) with +/-250 kg of initial body weight were
      randomly assigned in individual pens and fed the same diet for 106 days. At the
      end of the trial, all the animals were slaughtered and the pH, temperature, and
      weight of the carcass were recorded. The right side of each carcass was then
      separated into chuck, shoulder, flank sirloin, and round for evaluation of
      commercial cuts yield. The left carcass sides were ribbed between the 12th and
      13th ribs where the rib eye area and fat thickness measurements were taken. The
      9th-11th rib section was removed from the left half carcass and then dissected
      into muscle, fat, and bones in order to estimate carcass composition. Gender had
      no effect (P > 0.05) on performance, intake, digestibility of dry matter and all
      the nutrients evaluated, feed efficiency, and carcass characteristics. It can be
      concluded that steers and heifers (spayed or not) have the same potential to
      produce beef. From a productive and welfare standpoint, there is no reason to
      spay heifers.

PMID- 22160604
TI  - Naturally occurring genetic variability in expression of Gsta4 is associated with
      differential survival of axotomized rat motoneurons.
AB  - A large number of molecular pathways have been implicated in the degeneration of
      axotomized motoneurons. We previously have demonstrated substantial differences
      in the survival rate of axotomized motoneurons across different rat strains.
      Identification of genetic differences underlying such naturally occurring strain
      differences is a powerful approach, also known as forward genetics, to gain
      knowledge of mechanisms relevant for complex diseases, like injury-induced
      neurodegeneration. Overlapping congenic rat strains were used to fine map a gene
      region on rat chromosome eight previously shown to regulate motoneuron survival
      after ventral root avulsion. The smallest genetic fragment, R5, contains 35 genes
      and displays a highly significant regulatory effect on motoneuron survival.
      Furthermore, expression profiling in a F2(DAxPVG) intercross demonstrates one
      single cis-regulated gene within the R5 fragment; Gsta4, encoding glutathione S
      transferase alpha-4. Confirmation with real-time PCR shows higher Gsta4
      expression in PVG compared with DA both in naive animals and at several time
      points after injury. Immunolabeling with a custom made rat Gsta4 antibody
      demonstrates a neuronal staining pattern, with a strong cytoplasmic labeling of
      motoneurons. These results demonstrate and map naturally occurring genetic
      differences in the expression of Gsta4 is associated both with a highly
      significant increase in the survival of axotomized motoneurons and with a trans
      regulation of several molecular pathways involved in neurodegenerative processes.
      This adds to a large body of evidence implicating lipid peroxidation as an
      important pathway for neurodegeneration.

PMID- 22160606
TI  - Evaluation of a website providing information on regional health care services
      for patients with rheumatoid arthritis: an observational study.
AB  - Studies on the effectiveness of information provision for patients with arthritis
      through the Internet are scarce. This study aimed to describe rheumatoid
      arthritis (RA) patients' knowledge and information needs before and after
      launching a website providing information on regional health care services for
      patients with rheumatic conditions. The intervention consisted of a weekly
      updated website comprising practical information on regional health care services
      for patients with arthritis. In addition, patients were offered information
      leaflets and an information meeting. Before (T1) and 24 months after (T2) the
      website was launched, a random sample of 400 RA patients filled in a
      questionnaire regarding knowledge and information need (scores 0-18) about
      accessibility and contents of 18 regional health care services. Two hundred and
      fifty-one patients returned the questionnaire (response rate 63%) at T1 and 200
      patients (50%) at T2, respectively, with 160 paired observations (112 females
      (70%), mean age 60.4 years (SD 9.9)). The total score for insufficient knowledge
      about contents decreased from 9.3 (SD 4.9) to 8.5 (SD 4.8; p = 0.03) and for
      accessibility from 8.6 (SD 4.7) to 8.4 (SD 4.9; p = 0.59). Total score for
      information need about contents decreased from 4.2 (SD 4.5) to 1.9 (SD 2.9; p <
      0.01) and for accessibility from 3.6 (SD 4.5) to 1.4 (SD 2.4; p < 0.01) (paired t
      tests).After the administration of a website comprising practical health care
      information, RA patients' information need and to a lesser extent their
      perception of having insufficient knowledge on relevant regional health care
      services decreased significantly. The results of this descriptive study suggest
      that the use of the Internet to inform patients may be effective, although
      controlled studies are required to evaluate and optimize web-delivered
      information.

PMID- 22160607
TI  - Acting in perspective: the role of body and language as social tools.
AB  - We investigated how the reach-to-grasp movement is influenced by the presence of
      another person (friend or non-friend), who was either invisible (behind) or
      located in different positions with respect to an object and to the agent, and by
      the perspective conveyed by linguistic pronouns ("I", "You"). The interaction
      between social relationship and relative position influenced the latency of both
      maximal fingers aperture and velocity peak, showing shorter latencies in the
      presence of a non-friend than in the presence of a friend. However, whereas the
      relative position of a non-friend did not affect the kinematics of the movement,
      the position of a friend mattered: latencies were significantly shorter with
      friends only in positions allowing them to easily reach for the object. Finally,
      the investigation of the overall reaching movement time showed an interaction
      between the speaker and the pronoun: participants reached the object more quickly
      when the other spoke, particularly if she used the "I" pronoun. This suggests
      that speaking, and particularly using the "I" pronoun, evokes a potential action.
      Implications of the results for embodied cognition are discussed.

PMID- 22160608
TI  - Putty lung: pulmonary parenchymal calcification due to tuberculosis.

PMID- 22160609
TI  - Chondromyxoid fibroma of the rib with prominent exophytic configuration.
AB  - Chondromyxoid fibroma (CMF) of the rib is exceedingly unusual and few detailed
      image findings have been reported. Plain radiograph, computed tomography (CT),
      and magnetic resonance (MR) imaging findings and pathological aspects of a case
      of CMF of the right 2nd rib in a 15-year-old woman are reported, which was
      difficult to diagnose preoperatively. Though it is challenging to diagnose CMF
      preoperatively, it is important to be aware that CMF can exhibit atypical
      prominent exophytic features in unexpected locations such as the ribs.

PMID- 22160610
TI  - Recognition, assessment, and treatment of non-union after surgical fixation of
      fractures: emphasis on 3D CT.
AB  - For the post-operative patient, conventional axial computed tomography (CT)
      imaging and 2D multiplanar reconstruction are of limited value because of the
      beam-hardening artifact. However, three-dimensional (3D) CT imaging is an
      effective means of detecting subtle fracture healing, or confirming non-union,
      and for evaluating the integrity of metal hardware. In this article we emphasize
      the advantages of 3D CT imaging in the assessment and preoperative planning of
      non-union for patients who have been surgically treated for fractures.

PMID- 22160611
TI  - Late potentials in the signal-averaged electrocardiogram in pre-pubertal children
      with ADHD, before and after methylphenidate treatment.
AB  - Reports on sudden cardiac death (SCD) of children and adolescents treated with
      stimulant agents have raised concerns regarding the need for cardiovascular
      monitoring and risk stratification schedules. Cardiac ventricular late potentials
      (LPs) represent delayed ventricular activation that might predispose to fatal
      ventricular arrhythmias and SCD in cardiac patients. LPs have not previously been
      measured in children with attention deficit/hyperactivity disorder (ADHD). LPs
      were measured in 18 physically healthy ADHD children (5 girls and 13 boys, age
      11.9 +/- 2.5 years, treatment duration 2.6 +/- 1.9 years) before and 2 h after
      oral methylphenidate administration. No significant changes were detected and LPs
      were found to be within normal ranges. In conclusion, this preliminary small
      scale study suggests that methylphenidate in physically healthy children with
      ADHD was not associated with cardiac ventricular LPs, suggesting the safety of
      the agent in this age group.

PMID- 22160612
TI  - Assessing pregnancy intention and associated risks in pregnant adolescents.
AB  - Unintended pregnancy and associated behaviors may play a substantial role in the
      increased risk of adverse maternal and neonatal outcomes associated with teen
      pregnancy. We evaluate a multi-dimensional measure of pregnancy intention among
      pregnant adolescents and quantify the association between intention dimensions
      and adverse outcomes and risk behaviors. Pregnancy intention measures were
      examined in a cohort of 300 pregnant adolescent women. We considered 18 items
      assessing elements of pregnancy intention including pregnancy planning, timing,
      emotional response, and readiness. Latent class analysis was performed to
      identify dimensions of pregnancy intention. Parsimonious scores were created by
      minimizing the number of covariates while maintaining substantial agreement with
      the latent class. Associations between intention measures and prenatal care, risk
      behaviors, and pregnancy outcomes were quantified using multivariable logistic
      regression. Two constructs of pregnancy intention were identified: planning and
      emotional readiness. Compared with emotionally ready adolescents, adolescents
      categorized as not emotionally ready had an increased odds of inadequate prenatal
      care (OR = 2.70, 95% CI:1.27-5.72), delayed prenatal care (OR = 2.54, 95% CI:1.27
      5.09), and self-reported depression at the time of the first prenatal visit (OR =
      2.21, 95% CI:1.03-4.77). Pregnancy planning was not associated with adverse
      pregnancy risk factors or outcomes. Among pregnant adolescents, emotional
      readiness for pregnancy and parenting was inversely associated with known risk
      factors for adverse pregnancy outcomes, suggesting that emotional readiness
      rather than pregnancy planning may be the more pertinent intention construct for
      adolescents.

PMID- 22160613
TI  - Dietary intakes of preschool-aged children in relation to caregivers'
      race/ethnicity, acculturation, and demographic characteristics: results from the
      2007 California Health Interview Survey.
AB  - Few studies have examined the influence of acculturation on dietary behaviors of
      young children while controlling for other demographic variables. The purpose of
      this study was to assess reported dietary intakes of preschool-aged children (3-5
      years) and subsequent associations with caregivers' race/ethnicity, acculturation
      and demographic characteristics, using data from the 2007 California Health
      Interview Survey (CHIS). Analysis was restricted to Hispanic and non-Hispanic
      white caregivers and their preschool-aged children (n = 1,105). Caregivers'
      acculturation was assessed using place of birth, duration of United States
      residence, and language spoken at home. Proxy-reports by caregivers to a dietary
      screener were used to estimate children's intakes of fruit, 100% fruit juice,
      vegetables, sweets, and sugar-sweetened beverages consumed. In multivariate
      analyses, Hispanic caregivers reported their children consumed fewer servings of
      vegetables than did the children of non-Hispanic white caregivers; there were no
      other statistically significant differences in children's dietary intakes by
      caregivers' race/ethnicity. Caregivers' acculturation was associated with
      caregiver-reported consumption of sweets by children (beta = 0.09, 95%CI = 0.01
      0.18). Demographic characteristics that were associated with reported dietary
      intakes of children included caregivers' age, education, and geographic region of
      residence. In contrast to past studies of acculturation and diet in older
      children and adults, this study suggests that for 3-5 year olds, caregivers'
      level of acculturation does not play as strong a role in the dietary intakes of
      the younger children under their care.

PMID- 22160614
TI  - The dynamics of oral lichen planus: a retrospective clinicopathological study.
AB  - To evaluate disease dynamics, treatment results, and frequency of malignant
      transformation. Ten-year single center retrospective study. The study included
      171 patients, 28-99 years old. Follow-up was 1-16 years. 49.5% exhibited changes
      in clinical presentation, with 19% yearly increase of probability for type shift.
      Index of extent (number of oral locations) showed a mean 40% decrease and 94.1%
      reported improvement. There were significant differences between treated and
      untreated patients (P=0.012). Patients with or without systemic diseases had
      identical treatment requirements for oral lesions. The prevalence of SCC was
      5.8%. Oral lichen planus constantly changes presentation and extent of
      involvement. The effect of systemic diseases was insignificant in the present
      study. There is a clear value for treatment to reduce the extent of lesions. The
      results indicate that all clinical forms of the disease need to be equally
      followed since the clinical presentation typically changes over time, while
      malignant transformation can occur in all forms.

PMID- 22160616
TI  - Prognostic factors in transformed mycosis fungoides: a retrospective analysis of
      100 cases.
AB  - Large cell transformation (LCT) in mycosis fungoides (MF) is generally associated
      with an aggressive clinical course and poor survival, requiring aggressive
      therapeutic approach. However, a proportion of cases may follow an indolent
      clinical course. To identify prognostic factors, we analyzed the prognostic
      relevance of clinical, histologic, and immunophenotypical features in a large
      cohort of transformed MF patients, including 75 patients with only skin lesions,
      19 patients with LCT in skin and lymph nodes, and 6 patients with LCT in lymph
      nodes only. Multivariate analysis of the total group showed that CD30 negativity,
      folliculotropic MF, extent of skin lesions and extracutaneous transformation were
      associated with reduced disease-specific survival (DSS) and, except for CD30
      negativity and folliculotropic MF, also overall survival. In a multivariate
      analysis of 75 patients with only skin lesions at the time of LCT, CD30
      negativity, folliculotropic MF and extent of skin lesions were independent
      parameters for both DSS and overall survival. Using the most discriminating
      parameters as a prognostic index, in both study groups differences in DSS between
      patients with 0-1 unfavorable prognostic factor(s) and >= 2 unfavorable
      prognostic factors were statistically significant (P < .001). This prognostic
      index may be helpful in predicting prognosis and selecting the most appropriate
      treatment in patients with transformed MF.

PMID- 22160615
TI  - Prognostic significance of regulators of cell cycle and apoptosis, p16(INK4a),
      p53, and bcl-2 in primary mucosal melanomas of the head and neck.
AB  - Abnormalities in cell cycle regulation, tumor suppressor gene functions and
      apoptosis are frequent events in tumorigenesis. Their role in the pathogenesis
      and prognosis of primary mucosal melanomas (MM) of the upper aerodigestive tract
      remains unknown. Sixty-four patients (40 men, 24 women, median age 64 years) with
      MM were included in this study; 32 had tumors in the nasal/paranasal cavities, 28
      in the oral cavity and 4 in the pharynx. Archival tissues from 47 initial mucosal
      tumors, 17 mucosal recurrences, and 13 nodal/distant metastases were subjected to
      immunohistochemistry using antibodies against p16, p53, and bcl-2. The results
      were correlated with histological features and survival data. Expressions of p16,
      p53, and bcl-2 proteins were seen in 25% (N=19/76), 21% (N=16/76), and 74%
      (N=56/76) of all tumors, respectively. bcl-2 expression in the initial tumors was
      associated with significantly longer overall and disease specific survival (3.3
      vs. 1.5 years, P <= 0.05). Expression of p16 was increasingly lost, from 32% in
      initial tumors to 12% in recurrent and 15% in metastatic tumors (P=0.06). Tumors
      comprised of undifferentiated cells were significantly more p53 positive than
      epithelioid or spindle cells (80% vs. 33%, P=0.02). Expression of these markers
      did not correlate with necrosis, or vascular and/or deep tissue invasion.
      Expression of bcl-2 is associated with better survival in MM. Loss of p16 was
      seen with tumor progression whereas aberrant p53 expression was frequent in
      undifferentiated tumor cells.

PMID- 22160617
TI  - Assessment and prognostic value of the European LeukemiaNet criteria for
      clinicohematologic response, resistance, and intolerance to hydroxyurea in
      polycythemia vera.
AB  - Criteria of response and definition of resistance and intolerance to hydroxyurea
      (HU) in polycythemia vera (PV) were proposed by the European LeukemiaNet (ELN).
      Such criteria were evaluated in 261 PV patients (median follow-up, 7.2 years)
      treated with HU for a median of 4.4 years. Complete response, partial response,
      and no response were observed in 24%, 66%, and 10% of patients, respectively.
      Achieving ELN response (complete or partial) or hematocrit response did not
      result in better survival or less thrombosis and bleeding. On the contrary,
      having no response in leukocyte count was associated with higher risk of death
      (HR, 2.7; 95% confidence interval [CI], 1.3%-5.4%; P = .007), whereas lack of
      response in platelet count involved a higher risk of thrombosis and bleeding.
      Resistance and intolerance to HU was registered in 11% and 13% of patients,
      respectively. Resistance to HU was associated with higher risk of death (HR, 5.6;
      95% CI, 2.7%-11.9%; P < .001) and transformation (HR, 6.8; 95% CI, 3.0%-15.4%; P
      < .001). In summary, fulfilling the ELN definition for response to HU was not
      associated with a benefit in the clinical outcome in PV, whereas response in
      platelet and white blood cell counts were predictive of less thrombohemorrhagic
      complications and better prognosis, respectively. Resistance to HU was an adverse
      prognostic factor.

PMID- 22160619
TI  - Risk of complications during hematopoietic stem cell collection in pediatric
      sibling donors: a prospective European Group for Blood and Marrow Transplantation
      Pediatric Diseases Working Party study.
AB  - We investigated prospectively factors influencing the safety of hematopoietic
      stem cell (HSC) collection in 453 pediatric donors. The children in the study
      donated either BM or peripheral blood stem cells (PBSCs) according to center
      policy. A large variability in approach to donor issues was observed between the
      participating centers. Significant differences were observed between BM and PBSC
      donors regarding pain, blood allotransfusion, duration of hospital stay, and iron
      supplementation; however, differences between the groups undergoing BM vs PBSC
      donation preclude direct risk comparisons between the 2 procedures. The most
      common adverse event was pain, reported mainly by older children after BM
      harvest, but also observed after central venous catheter (CVC) placement for PBSC
      collection. With regard to severe adverse events, one patient (0.7%) developed a
      pneumothorax with hydrothorax after CVC placement for PBSC collection. The risk
      of allotransfusion after BM harvest was associated with a donor age of < 4 years
      and a BM harvest volume of > 20 mL/kg. Children < 4 years were at higher risk
      than older children for allotransfusion after BM harvest and there was a higher
      risk of complications from CVC placement before apheresis. We conclude that PBSC
      and BM collection are safe procedures in children.

PMID- 22160618
TI  - Enhanced outgrowth of EBV-transformed chronic lymphocytic leukemia B cells
      mediated by coculture with macrophage feeder cells.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the clonal
      expansion of CD5-expressing B lymphocytes that produce mAbs often reactive with
      microbial or autoantigens. Long-term culture of B-CLL clones would permit the
      collection and characterization of B-CLL mAbs to study antigen specificity and of
      B-CLL DNA to investigate molecular mechanisms promoting the disease. However, the
      derivation of long-term cell lines (eg, by EBV), has not been efficient. We have
      improved the efficiency of EBV B-CLL transformation of CpG oligonucleotide
      stimulated cells by incubating patient peripheral blood mononuclear cells in the
      presence of an irradiated mouse macrophage cell line, J774A.1. Using this
      approach, peripheral blood mononuclear cells isolated from 13 of 21 B-CLL
      patients were transformed as documented by IGHV-D-J sequencing. Four clones grew
      and retained CD5 expression in culture for 2 to 4 months. However, despite
      documentation of EBV infection by expression of EBNA2 and LMP1, B-CLL cells died
      after removal of macrophage feeder cells. Nevertheless, using electrofusion
      technology, we generated 6 stable hetero-hybridoma cell lines from EBV
      transformed B-CLL cells, and these hetero-hybridomas produced immunoglobulin.
      Thus, we have established enhanced methods of B-CLL culture that will enable
      broader interrogation of B-CLL cells at the genetic and protein levels.

PMID- 22160620
TI  - Defective nuclear localization of Hsp70 is associated with dyserythropoiesis and
      GATA-1 cleavage in myelodysplastic syndromes.
AB  - Normal human erythroid cell maturation requests the transcription factor GATA-1
      and a transient activation of caspase-3, with GATA-1 being protected from caspase
      3-mediated cleavage by interaction with the chaperone heat shock protein 70
      (Hsp70) in the nucleus. Erythroid cell dysplasia observed in early
      myelodysplastic syndromes (MDS) involves impairment of differentiation and excess
      of apoptosis with a burst of caspase activation. Analysis of gene expression in
      MDS erythroblasts obtained by ex vivo cultures demonstrates the down-regulation
      of a set of GATA-1 transcriptional target genes, including GYPA that encodes
      glycophorin A (GPA), and the up-regulation of members of the HSP70 family. GATA-1
      protein expression is decreased in MDS erythroblasts, but restores in the
      presence of a pan-caspase inhibitor. Expression of a mutated GATA-1 that cannot
      be cleaved by caspase-3 rescues the transcription of GATA-1 targets, and the
      erythroid differentiation, but does not improve survival. Hsp70 fails to protect
      GATA-1 from caspases because the protein does not accumulate in the nucleus with
      active caspase-3. Expression of a nucleus-targeted mutant of Hsp70 protects GATA
      1 and rescues MDS erythroid cell differentiation. Alteration of Hsp70 cytosolic
      nuclear shuttling is a major feature of MDS that favors GATA-1 cleavage and
      differentiation impairment, but not apoptosis, in dysplastic erythroblasts.

PMID- 22160621
TI  - Chore or priority? Barriers and facilitators affecting dilator use after pelvic
      radiotherapy for gynaecological cancer.
AB  - PURPOSE: Pelvic radiotherapy for gynaecological cancer often leads to damage of
      the vaginal mucosa, resulting in stenosis (obstruction by scar tissue). Stenosis
      has been associated with sexual dysfunction and can hinder medical examinations
      to detect recurrence. The use of vaginal dilators is frequently recommended to
      prevent or minimise stenosis, but women are reluctant to use these devices. The
      aim of this study was to explore the patient experience of dilator use and
      identify the barriers and facilitators affecting compliance with clinician
      recommendations. METHODS: Women were eligible for the study if they had undergone
      pelvic radiotherapy for gynaecological cancer up to 2 years ago and received a
      vaginal dilator as part of their post-treatment rehabilitation. Fifteen
      participants completed a semi-structured interview. RESULTS: Barriers to dilator
      use included: uncertainty about how/when to use dilators, viewing it as a
      negative experience, lack of time or forgetting and the need for discretion due
      to an association with sex aids. Facilitators included: concern about stenosis,
      belief that dilators work, reminders of stenosis, acceptance of dilator use as
      part of their normal routine or an extension of medical treatment and focusing on
      positive aspects. These factors were incorporated into a model of dilator use
      based on the Health Belief Model. CONCLUSIONS: This is the first qualitative
      study to specifically investigate the patient experience of dilator use. The
      barriers and facilitators identified in this study and the proposed theory-based
      model provide new insights to inform future research and clinical management of
      dilator use.

PMID- 22160622
TI  - Validation of the Chinese version of the Gamblers' Belief Questionnaire (GBQ-C).
AB  - A growing body of evidence is documenting the significant role of cognitive
      factors in influencing gambling behaviors. Although measures of cognitive biases
      have been developed, further validation of these scales is needed among non
      Western samples. The 21-item Gamblers' Belief Questionnaire was originally
      developed and validated by Steenbergh et al. (in Psychol. Addict. Behav., 16: 143
      149, 2002). The scale then has been widely used in the gambling research of the
      West. The present study was designed to examine and validate the Chinese version
      of Gamblers' Belief Questionnaire (GBQ-C) using 258 Chinese participants.
      Confirmatory factor analyses indicated the 2-factor model provided a good fit to
      the data as evidenced by various model fit indices (CFI = .91, RMSEA = .08 and
      SRMR = .05). Additional evidence for the validity of the GBQ-C was provided by
      significant correlations with other relevant measures (range .40-.75). In sum,
      the present study provides support for the GBQ-C as a valuable tool for assessing
      gambling cognitions among Chinese samples.

PMID- 22160623
TI  - Geographical differentiation of the molecular diversity of cacao swollen shoot
      virus in Togo.
AB  - The variability of cacao swollen shoot virus (CSSV) was studied in two areas of
      Togo with distinct epidemiological backgrounds, Kloto and Litime. This molecular
      study was based on 120 sequence comparisons of the first part of ORF3 of the
      viral genome. The phylogenetic study distinguished three groups of CSSV isolates,
      A, B, and C, with clear geographical differentiation between the Kloto and Litime
      areas. The only group detected in Kloto was group C, whereas the Litime area only
      contained isolates from groups A and B, which most probably originated from
      Ghana. The divergence between the three groups strongly suggests a different
      origin for each of the groups.

PMID- 22160624
TI  - HIV-infection resistance in PMBC-derived dendritic cells modified with
      recombinant virus.
AB  - This study aimed to identify the characteristics of recombinant-adenovirus
      modified PBMC-derived dendritic cells and their resistance to HIV-1 infection by
      integrating the CCR5?32, CCR5siRNA, HIV-1 pol and HIV-1 int genes into a
      recombinant adenovirus vector using the AdEasy system. Dendritic cells (DCs) were
      isolated from human PBMCs from blood of healthy donors. The expression of
      CCR5?32, CCR5, CXCR4 and HIV-1 p24 in PBMCs or modified cells was measured by
      western blot, p24 expression in cell lysates was measured by ELISA, and HIV-1
      entry was measured by beta-galactosidase assay. Furthermore, T-cell immunity
      induced by the recombinant adenovirus was measured by ELISPOT assay. After the
      cells were modified by Ad-R5?32siRNA, the expression of CCR5?32 increased, while
      the expression of CCR5 and CXCR4 decreased. There was no adverse effect of
      adenoviral gene transfer on DC development. CD83 expression on the surface of
      mature DCs did not change after gene transfer. The expression of p24 remained at
      low levels in modified cells when challenged by HIV-1. The modified cells showed
      resistance to HIV-1 infection. Results indicated that recombinant-adenovirus
      modified cells demonstrated good resistance to HIV-1 infection. Modification of
      HSC-derived immune cells, such as DCs, may be a potent strategy to resist HIV-1
      infection.

PMID- 22160626
TI  - Molecular simulation methods in drug discovery: a prospective outlook.
AB  - Over the last decades, molecular simulations have spread through the drug
      discovery arena. This trend is expected to continue in the foreseeable future
      thanks to increased performance and the positive impact they can exert on
      productivity. In this article we highlight three aspects of molecular modelling
      for which we expect significant improvements over the next 25 years. Increased
      computational resources, faster algorithms and novel methods to sample rare
      events will provide a better handle on target flexibility and its relation with
      ligand binding. More accurate target druggability predictions will improve the
      success, but also broaden the scope of target-based drug discovery strategies.
      Finally, the use of higher levels of theory will increase the accuracy of protein
      ligand binding affinity predictions, resulting in better hit identification
      success rates as well as more efficient lead optimization processes.

PMID- 22160625
TI  - Morocco underwent a drift of circulating hepatitis C virus subtypes in recent
      decades.
AB  - Hepatitis C virus (HCV) isolates circulating in Morocco are poorly documented. To
      determine the subgenotype distribution of HCV in chronically infected patients,
      serum samples from 185 anti-HCV-positive patients were analyzed. Determination of
      the HCV genotype and subtype was performed by sequencing the 5'UTR, NS5B and core
      regions. According to the NS5B phylogeny, the HCV strains primarily belonged to
      subtypes 1b (75.2%), 2i (19.1%) and 2k (2.8%). Using a Bayesian approach, the
      mean date of appearance of the most recent common ancestor was estimated to be
      1910 for HCV-1b and 1854 for HCV-2i. Although it is currently the most frequent
      genotype in Morocco and the dominant form in hepatocellular carcinoma, it thus
      appears that HCV-1b was introduced into the population subsequently to HCV-2i.

PMID- 22160627
TI  - Beta-elemene inhibits Hsp90/Raf-1 molecular complex inducing apoptosis of
      glioblastoma cells.
AB  - beta-Elemene, an active component of herb medicine Curcuma wenyujin, has been
      shown to antagonize glioblastoma cells by inducing apoptosis. However, how beta
      elemene induces apoptosis of these cells remains unclear. In this study, we
      report that beta-elemene disrupted the formation of the Hsp90/Raf-1 complex, a
      key step in maintaining the conformation stability of Raf-1, and caused
      deactivation of Raf-1 and inhibition of the ERK pathway, thereby leading to
      apoptosis of glioblastoma cells. Specifically, treatment of glioblastoma cell
      lines with beta-elemene attenuated phosphorylation of multiple members of the
      kinase families in the Ras/Raf/MEK/ERK cascade, including Raf-1 and ERK as well
      as downstream signaling targets such as Bcl-2. These results suggest that the
      Hsp90/Raf-1 complex could be a promising molecular target for new drug
      development for the treatment of glioblastoma.

PMID- 22160628
TI  - Health-related quality of life and biomarkers in breast cancer survivors
      participating in tai chi chuan.
AB  - INTRODUCTION: Breast cancer survivors experience diminished health-related
      quality of life (HRQOL). We report on the influence of tai chi chuan exercise
      (TCC) on HRQOL and explore associations between changes in HRQOL and biomarkers.
      METHODS: Breast cancer survivors (N = 21) were randomly assigned to TCC or
      standard support therapy (SST) for 12 weeks (three times/week; 60 min/session).
      Interleukin-6, interleukin-8 (IL-8), insulin-like growth factor-1 (IGF-1),
      insulin-like growth factor-binding protein (IBFBP)-1, IGFBP-3, glucose, insulin,
      and cortisol were measured pre- and postintervention. Overall HRQOL and
      subdomains were assessed at preintervention (T1), midintervention (T2) and
      postintervention (T3) and biomarkers at T1 and T3. RESULTS: The TCC group
      improved in total HRQOL (T1-T2:CS = 8.54, P = 0.045), physical functioning (T1
      T2:CS = 1.89, P = 0.030), physical role limitations (T1-T2 CS = 1.55, P = 0.023),
      social functioning (T1-T3:CS = 1.50, P = 0.020), and general mental health (T1
      T2:CS = 2.67, P = 0.014; T1-T3:CS = 2.44, P = 0.019). The SST improved in social
      functioning (T1-T2:CS = 0.64, P = 0.043) and vitality (T1-T2:CS = 0.90, P =
      0.01). There were relationships between changes in IGF-1 and overall HRQOL (r = 
      0.56; P < 0.05), physical role limitation (r = -0.68; P < 0.05), and social
      functioning (r = -0.56; P < 0.05). IGFBP-1 changes were associated with physical
      role limitations changes (r = 0.60; P < 0.05). IGFBP-3 changes were associated
      with physical functioning changes (r = 0.46; P <= 0.05). Cortisol changes were
      associated with changes in physical role limitations (r = 0.74; P < 0.05) and
      health perceptions (r = 0.46; P < 0.05). Glucose changes were associated with
      emotional role limitation changes (r = -0.70; P < 0.001). IL-8 changes were
      associated with emotional role limitation changes (r = 0.59; P < 0.05).
      DISCUSSION/CONCLUSIONS: TCC may improve HRQOL by regulating inflammatory
      responses and other biomarkers associated with side effects from cancer and its
      treatments. IMPLICATIONS FOR CANCER SURVIVORS: TCC may be an intervention capable
      of improving HRQOL in breast cancer survivors.

PMID- 22160629
TI  - A randomized trial of exercise on well-being and function following breast cancer
      surgery: the RESTORE trial.
AB  - OBJECTIVES: This study aimed to determine the effect of a moderate, tailored
      exercise program on health-related quality of life, physical function, and arm
      volume in women receiving treatment for nonmetastatic breast cancer. METHODS:
      Women who were within 4-12 weeks of surgery for stage I-III breast cancer were
      randomized to center-based exercise and lymphedema education intervention or
      patient education. Functional assessment of cancer therapy-breast cancer (FACT
      B), 6-min walk, and arm volume were performed at 3-month intervals through 18
      months. Repeated measures analysis of covariance was used to model the total
      meters walked over time, FACT-B scores, and arm volume. Models were adjusted for
      baseline measurement, baseline affected arm volume, number of nodes removed, age,
      self-reported symptoms, baseline SF-12 mental and physical component scores,
      visit, and treatment group. RESULTS: Of the recruited 104 women, 82 completed all
      18 months. Mean age (range) was 53.6 (32-82) years; 88% were Caucasian; 45% were
      employed full time; 44% were overweight; and 28% obese. Approximately, 46% had
      breast-conserving surgery; 79% had axillary node dissection; 59% received
      chemotherapy; and 64% received radiation. The intervention resulted in an average
      increase of 34.3 ml (SD = 12.8) versus patient education (p = 0.01). Changes in
      FACT-B scores and arm volumes were not significantly different. CONCLUSIONS: With
      this early exercise intervention after breast cancer diagnosis, a significant
      improvement was achieved in physical function, with no decline in health-related
      quality of life or detrimental effect on arm volume. IMPLICATIONS FOR CANCER
      SURVIVORS: Starting a supervised exercise regimen that is tailored to an
      individual's strength and stamina within 3 months following breast cancer surgery
      appears safe and may hasten improvements in physical functioning.

PMID- 22160631
TI  - Physical attributes, limitations, and future potential for PET and SPECT.
AB  - Advances in SPECT and PET imaging hardware, software, and radiotracers are vastly
      improving the non-invasive evaluation of myocardial perfusion and function. In
      contrast to traditional dual-headed, sodium iodide crystal and photomultiplier
      cameras with mechanical collimators, new SPECT camera designs utilize novel,
      collimators, and solid-state detectors that convert photons directly to
      electrical signals. These cameras simultaneously collect data from as many as 76
      small detectors narrowly focused on the heart. New noise regularization and
      resolution recovery/noise reduction reconstruction software interprets emitted
      counts more efficiently and thus more effectively discriminates between useful
      signals and noise. As a result, shorter acquisition times and/or lower tracer
      doses produce higher quality SPECT images than were possible before. PET
      perfusion imaging has benefitted from the introduction of novel detectors that
      now allow true 3D imaging, new radiopharmaceuticals, and precise attenuation
      correction (AC). These developments have resulted in perfusion images with higher
      spatial and contrast resolution that may be acquired in shorter protocols and/or
      with less patient radiation exposure than traditional SPECT. Hybrid SPECT/CT and
      PET/CT cameras utilize transmission computed tomographic (CT) scans for AC, and
      offer the additional clinical advantages of evaluating coronary calcium,
      myocardial anatomy (including non-invasive CT angiography), myocardial function,
      and myocardial perfusion in a single imaging procedure.

PMID- 22160630
TI  - Reduced septal glucose metabolism predicts response to cardiac resynchronization
      therapy.
AB  - BACKGROUND: Up to 50% of patients do not respond to Cardiac Resynchronization
      Therapy (CRT). Recent work has focused on quantifying mechanical dyssynchrony and
      left ventricular scar. Septal reverse-mismatch (R-MM) (reduced FDG uptake vs
      perfusion) has been observed in patients with cardiomyopathy and prolonged QRS
      duration. We hypothesized that a greater quantity of septal R-MM would indicate a
      greater potential for reversibility of the cardiomyopathy, when the dyssynchrony
      is improved with CRT. Therefore, this study's objective was to assess whether
      greater septal R-MM pattern predicts response to CRT. METHODS AND RESULTS: Forty
      nine patients had pre-implant Rubidium-82 and Fluorine-18-fluorodeoxyglucose PET
      scanning. Total and regional left ventricular scar size and extent of R-MM were
      calculated. Response to CRT was defined as >=10% improvement in left ventricular
      end-systolic volume or >=5% absolute ejection fraction improvement. In the non
      ischemic cardiomyopathy subset non-responders had significantly less septal R-MM
      than responders (13.1% compared to 27.1%, P = .012). There were correlations
      between the extent of septal R-MM and the increase in ejection fraction (r =
      0.692, P = .0004) and reduction in left ventricular end-systolic volume (r = 
      0.579, P = .004). For each 5% absolute increase in extent of septal R-MM the odds
      ratio of being a responder was 2.17 (95% CI 1.15, 4.11, P = .017). Extent of
      septal R-MM displayed high sensitivity and specificity (area under curve = 0.855,
      P = .017) to predict response. CONCLUSIONS: In patients with non-ischemic
      cardiomyopathy, greater extent of septal glucose metabolic R-MM pattern,
      predicted response to CRT. This parameter may be useful for identifying patients
      who benefit from CRT.

PMID- 22160632
TI  - Ion levels in the gastrointestinal tract content of freshwater and marine
      estuarine teleosts.
AB  - This study investigated the relationship between ion levels (Na+, Cl-, K+, Ca2+,
      and Mg2+) in the fluid phase and total chyme of the contents of the
      gastrointestinal tract segments of freshwater and marine-estuarine teleosts
      collected in different salinities (0-34 ppt) in estuarine and freshwater portions
      of the Sao Goncalo channel, southern Brazil. In addition, the relative
      contribution of feeding and osmoregulation to the ionic content of each portion
      of the gastrointestinal tract of fishes collected in different ambient salinities
      was analyzed. There was no relationship between salinity and ion levels in the
      fluid phase and total chyme of the segments of the gastrointestinal tract when
      considering all species together. However, there was a significant positive
      relationship between salinity and ion levels in the fluid phase and total chyme
      of two fish species (Micropogonias furnieri and Genidens barbus) collected in
      three or more different salinities. In most species, ion levels in the fluid
      phase and total chyme changed throughout the gastrointestinal tract, suggesting
      absorption, but the ionoregulatory mechanisms of the gastrointestinal tract seem
      to vary according to species.

PMID- 22160633
TI  - Daily variance of urinary excretion of AQP2 determined by sandwich ELISA method.
AB  - BACKGROUND: Urinary excretion of aquaporin 2 (AQP2) is a useful marker of kidney
      collecting duct function. A specific and convenient method to measure AQP2 in
      human urine would help to treat water balance disorders. It is unknown whether
      urinary excretion of AQP2 shows any daily variance. METHODS: A sandwich enzyme
      linked immunosorbent assay (ELISA) method for AQP2 was established using two
      different kinds of antibodies, and its sensitivity and specificity were examined.
      Daily variance of urinary excretion of AQP2 and responses to acute water load
      were examined. RESULTS: The established ELISA specifically detected urine AQP2
      with high sensitivity (detected as low as 0.34 pmol/mL). Urinary excretion of
      AQP2 did not show daily variance between 9 a.m. and 9 p.m. in healthy subjects.
      CONCLUSIONS: The developed ELISA method using two different antibodies is
      convenient and highly sensitive, and could be useful in clinical practice.
      Urinary excretion of AQP2 is relatively constant from morning to night, and spot
      urine sampling at any time during this time period does not affect the results.

PMID- 22160634
TI  - Vesicular glutamate transporter-3 contributes to visceral hyperalgesia induced by
      Trichinella spiralis infection in rats.
AB  - BACKGROUND: According to a recent study, vesicular glutamate transporter-3
      (VGLUT3) contributes to injury-induced mechanical hyperalgesia in mice. AIMS: The
      aims of the study were to investigate whether VGLUT3 is involved in visceral
      pain, and whether transient intestinal infection or acute cold restraint stress
      (ACRS) affects VGLUT3 expression levels in rats. METHODS: Changes in VGLUT3 and c
      Fos proteins were evaluated in rats which received noxious colorectal distension
      (CRD) stimulation. Transient intestinal infection was effected by oral
      administration of Trichinella spiralis (T. spiralis) larvae in Brown Norway rats.
      On the 100th day post-infection (PI), half of the PI-rats and non infected
      controls were subjected to an ACRS procedure. The visceromotor response to CRD
      was measured using the abdominal withdrawal reflex (AWR) score.
      Immunofluorescence and western blot analysis were used to estimate the expression
      of VGLUT3 in both peripheral and central neurons. RESULTS: Noxious stimulation
      induced a significant increase in the expression of VGLUT3 in the L6S1 spinal
      dorsal horn. Compared with the control group, the pain threshold was
      significantly decreased in the ACRS, PI, and PI + ACRS groups. VGLUT3 expression
      in the L6S1 dorsal root ganglion (DRG) and spinal neurons were significantly
      increased in PI and PI + ACRS groups as compared with the control group.
      CONCLUSIONS: VGLUT3 is involved in conduction of visceral pain sensation and in
      visceral hyperalgesia induced by Trichinella spiralis infection in rats.

PMID- 22160635
TI  - Genetic variation in the peroxisome proliferator activated receptor-gamma gene is
      associated with histologically advanced NAFLD.
AB  - BACKGROUND: The peroxisome proliferator activated receptor-gamma (PPARG) is a
      nuclear receptor that regulates adipocyte differentiation, insulin sensitivity
      and lipid metabolism, thus, it represents a good candidate gene for non-alcoholic
      fatty liver disease (NAFLD). PURPOSE AND METHOD: We investigated the association
      of two PPARG variants (Pro12Ala and C1431T) with NAFLD and its histological
      features. DNA was extracted from 274 archived, formalin-fixed liver biopsy
      specimens from 212 patients with NAFLD and 62 controls with normal liver
      histology. RESULTS: Individual SNPs did not show significant association with
      NAFLD or its histological features. A haplotype comprised of both minor alleles
      (GT) was less enriched whereas a haplotype comprised of the two major alleles
      (CC) was more enriched in subjects with NAFLD compared to controls [9.3% vs.
      28.1% for GT (P = 0.001, OR 0.26 (range 0.14-0.48) and 80.4% vs. 64.8% for CC (P
      = 0.037, OR 2.23 (range 1.30-3.81)]. Both haplotypes were significantly
      associated with steatosis and fibrosis. The GT haplotype was also associated with
      lobular inflammation. CONCLUSIONS: Genetic variation in PPARG is associated with
      NAFLD, and the GT haplotype is associated with inflammatory and fibrotic changes
      that denote histologically advanced NAFLD.

PMID- 22160636
TI  - Efficacy of high-dose intra-dermal hepatitis B virus vaccine in previous
      vaccination non-responders with chronic liver disease.
AB  - BACKGROUND: Hepatitis B virus (HBV) vaccination is essential in chronic liver
      disease (CLD), because it can help prevent acute-on-chronic disease, which has
      potentially fatal complications. Unfortunately, this group has a significant
      proportion of HBV vaccination non-responders. A variety of intra-muscular (IM)
      vaccination methods have been used in an attempt to remedy this poor-response,
      but with limited success. AIMS: Herein is reported the safety and efficacy of
      high-dose intra-dermal (ID) HBV vaccination in CLD individuals who had failed
      previous IM standard and boost-dosing regimens. METHODS: Forty-eight CLD
      individuals, known HBcAb negative, who had failed both a three-dose schedule of
      40 MUg IM vaccination, and boost dosing of either 40 or 80 MUg IM, were
      identified, of which 42 completed the vaccination course. Each received a 40 MUg
      ID total dose (20 MUg per arm) during their clinic visits until a response was
      documented or a maximum of three doses had been administered. HBsAb titer >= 10
      mIU/ml was regarded as an immunologic response; the intention was to achieve an
      optimum response of >= 100 mIU/ml. RESULTS: Twenty-nine of forty-two (69%)
      individuals had an immunologic response, with 15 (51%) of the responders having
      the optimum response. No changes in serologic data occurred. No serious
      dermatologic reactions were observed. No differences between those who responded
      and those who did not were observed with regard to the presence of cirrhosis,
      diabetes mellitus, or chronic kidney disease. CONCLUSIONS: High-dose ID HBV
      vaccination of previous CLD non-responders to the standard IM regimen with boost
      dosing is both safe and efficacious, and should be considered for all such
      groups.

PMID- 22160637
TI  - TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant
      anthracyclines in high-risk breast cancer patients.
AB  - HER2 amplification, TOP2A aberrations, and absence of tissue inhibitor of
      metalloproteinase (TIMP-1) expression in breast carcinomas have been shown to be
      associated with incremental benefit from anthracycline-containing adjuvant
      chemotherapy, and this study was undertaken to validate these findings in a
      similar, but independent, randomized clinical trial. TIMP-1 was examined by
      immunohistochemistry in archival tumor tissue from 403 of 716 premenopausal high
      risk patients with known HER2 and TOP2A status who were randomized to
      cyclophosphamide, epirubicin, and fluorouracil (CEF) or cyclophosphamide,
      methotrexate, and fluorouracil (CMF) in the MA.5 trial. Ninety-eight (24%)
      patients had no TIMP-1 staining of tumor cells, 27% were HER2 amplified, and 18%
      were TOP2A aberrant. Forty-four percentage was classified as HT responsive (HER2
      amplified and/or TIMP-1 negative) and 37% as 2T responsive (TOP2A aberrant and/or
      TIMP-1 negative). There was no heterogeneity in treatment effect of CEF versus
      CMF according to TIMP-1. In HT-responsive patients, CEF was superior to CMF with
      an improved RFS (adjusted HR, 0.64; 95% CI, 0.42-0.97), but this was not
      significant for OS (adjusted HR, 0.66; 95% CI, 0.42-1.04). A significant HT
      profile versus treatment interaction was detected for OS (P = 0.03). In 2T
      responsive patients, CEF seemed to improve RFS compared to CMF (adjusted HR,
      0.67; 95% CI, 0.43-1.03) and improved OS (adjusted HR, 0.58; 95% CI, 0.36-0.93).
      A significant 2T profile versus treatment interaction was detected for OS (P =
      0.01). With this study, we validate a more substantial reduction in mortality by
      CEF compared to CMF in patients with an HT- or 2T-responsive profile; however, we
      could not show a similarly significant reduction in RFS events, where a benefit
      of CEF over CMF was found irrespective of TIMP-1 status. Further studies are
      necessary before the HT and 2T profiles may be used to direct the use of
      anthracyclines.

PMID- 22160638
TI  - Comparison of two nomograms to predict pathologic complete responses to
      neoadjuvant chemotherapy for breast cancer: evidence that HER2-positive tumors
      need specific predictors.
AB  - The aim of this study is to compare two published nomograms, the "Institut
      Gustave Roussy/M.D. Anderson Cancer Center" (IGR/MDACC) and the Colleoni
      nomograms, in predicting pathologic complete responses (pCR) to preoperative
      chemotherapy in an independent cohort and to assess the impact of HER2 status.
      Data from 200 patients with breast carcinoma treated with preoperative
      chemotherapy were collected. We calculated pCR rate predictions with the two
      nomograms and compared the predictions with the outcomes. Sixty percent of the
      patients with HER2-positive tumors received trastuzumab concomitantly with
      taxanes. Model performances were quantified with respect to discrimination and
      calibration. In the whole population, the area under the ROC curve (AUC) for the
      IGR/MDACC nomogram and the Colleoni nomogram were 0.74 and 0.75, respectively.
      Both of them underestimated the pCR rate (P = 0.026 and 0.0005). When patients
      treated with trastuzumab were excluded, the AUC were excellent: 0.78 for both
      nomograms with no significant difference between the predicted and the observed
      pCR (P = 0.14 and 0.15). When the specific population treated with trastuzumab
      preoperatively was analyzed, the AUC for the IGR/MDACC nomogram and the Colleoni
      nomogram were poor, 0.52 and 0.53, respectively. The IGR/MDACC and the Colleoni
      nomograms were accurate in predicting the probability of pCR after preoperative
      chemotherapy in the HER2-negative population but did not correctly predict pCR in
      the HER2-positive patients who received trastuzumab. This suggests that responses
      to preoperative chemotherapy, including trastuzumab, are biologically driven and
      that a specific nomogram or predictor for HER2-positive patients has to be
      developed.

PMID- 22160639
TI  - Multilevel determinants of breast cancer survival: association with geographic
      remoteness and area-level socioeconomic disadvantage.
AB  - A major priority for cancer control agencies is to reduce geographical
      inequalities in cancer outcomes. While the poorer breast cancer survival among
      socioeconomically disadvantaged women is well established, few studies have
      looked at the independent contribution that area- and individual-level factors
      make to breast cancer survival. Here, we examine relationships between geographic
      remoteness, area-level socioeconomic disadvantage and breast cancer survival
      after adjustment for patients' socio-demographic characteristics and stage at
      diagnosis. Multilevel logistic regression and Markov chain Monte Carlo simulation
      were used to analyze 18,568 breast cancer cases extracted from the Queensland
      Cancer Registry for women aged 30-70 years diagnosed between 1997 and 2006 from
      478 Statistical Local Areas in Queensland, Australia. Independent of individual
      level factors, area-level disadvantage was associated with breast cancer survival
      (P = 0.032). Compared to women in the least disadvantaged quintile (quintile 5),
      women diagnosed while resident in one of the remaining four quintiles had
      significantly worse survival (OR 1.23, 1.27, 1.30, 1.37 for quintiles 4, 3, 2,
      and 1, respectively). Geographic remoteness was not related to lower survival
      after multivariable adjustment. There was no evidence that the impact of area
      level disadvantage varied by geographic remoteness. At the individual-level,
      Indigenous status, blue collar occupations and advanced disease were important
      predictors of poorer survival. A woman's survival after a diagnosis of breast
      cancer depends on the socio-economic characteristics of the area where she lives,
      independently of her individual-level characteristics. It is crucial that the
      underlying reasons for these inequalities be identified to appropriately target
      policies, resources and effective intervention strategies.

PMID- 22160640
TI  - Ethanol promotes mammary tumor growth and angiogenesis: the involvement of
      chemoattractant factor MCP-1.
AB  - Alcohol consumption is a risk factor for breast cancer in humans. Experimental
      studies indicate that alcohol exposure promotes malignant progression of mammary
      tumors. However, the underlying cellular and molecular mechanisms remain unclear.
      Alcohol induces a pro-inflammatory response by modulating the expression of
      cytokines and chemokines. Monocyte chemoattractant protein-1 (MCP-1), also known
      as chemokine (C-C motif) ligand 2, is a pro-inflammatory chemokine implicated in
      breast cancer development/malignancy. We investigated the role of MCP-1 in
      alcohol-promoted mammary tumor progression. Using a xenograft model, we
      demonstrated that alcohol increased tumor angiogenesis and promoted
      growth/metastasis of breast cancer cells in C57BL/6 mice. Alcohol up-regulated
      the expression of MCP-1 and its receptor CCR2 in breast cancer cells in vitro and
      in vivo. Using a three-dimensional tumor/endothelial cell co-culture system, we
      demonstrated MCP-1 regulated tumor/endothelial cell interaction and promoted
      tumor angiogenesis. More importantly, MCP-1 mediated alcohol-promoted
      angiogenesis; an antagonist of the MCP-1 receptor CCR2 significantly inhibited
      alcohol-stimulated tumor angiogenesis. The CCR2 antagonist abolished ethanol
      stimulated growth of mammary tumors in mice. We further demonstrated that MCP-1
      enhanced the migration, but not the proliferation of endothelial cells as well as
      breast cancer cells. These results suggest that MCP-1 plays an important role in
      ethanol-stimulated tumor angiogenesis and tumor progression.

PMID- 22160641
TI  - Fingolimod potentiates the effects of sunitinib malate in a rat breast cancer
      model.
AB  - Most of the antiangiogenic strategies used in oncology principally target
      endothelial cells through the vascular endothelial growth factor (VEGF) pathway.
      Multiple kinase inhibitors can secondarily reduce mural cell stabilization of the
      vessels by blocking platelet-derived growth factor receptor (PDGFR) activity.
      However, sphingosine-1-phosphate (S1P), which is also implicated in mural cell
      recruitment, has yet to be targeted in clinical practice. We therefore
      investigated the potential of a simultaneous blockade of the PDGF and S1P
      pathways on the chemotactic responses of vascular smooth muscle cells (VSMCs) and
      the resulting effects of this blockade on breast tumor growth. Due to crosstalk
      between the S1P and PDGF pathways, we used AG1296 and/or VPC-23019 to inhibit
      PDGFR-beta and S1PR1/S1PR3 receptors, respectively. We showed that S1PR1 and
      S1PR3 are the principal receptors that mediate the S1P chemotactic signal on rat
      VSMCs and that they act synergistically with PDGFR-beta during PDGF-B signaling.
      We also showed that simultaneous blockade of the PDGFR-beta and S1PR1/S1PR3
      signals had a synergistic effect, decreasing VSMC migration velocity toward
      endothelial cell and breast carcinoma cell-secreted cytokines by 65-90%. This
      blockade also strongly decreased the ability of VSMCs to form a three-dimensional
      cell network. Similar results were obtained with the combination of sunitinib
      malate (a VEGFR/PDGFR kinase inhibitor) and fingolimod (an S1P analog). Sunitinib
      malate is a clinically approved cancer treatment, whereas fingolimod is currently
      indicated only for treatment of multiple sclerosis. Orally administered, the
      combination of these drugs greatly decreased rat breast tumor growth in a
      syngeneic cancer model (Walker 256). This bi-therapy did not exert cumulative
      toxicity and histological analysis of the tumors revealed normalization of the
      tumor vasculature. The simultaneous blockade of these signaling pathways with
      sunitinib malate and fingolimod may provide an effective means of reducing tumor
      angiogenesis, and may improve the delivery of other chemotherapies.

PMID- 22160643
TI  - Positive and null effects of interprofessional education on attitudes toward
      interprofessional learning and collaboration.
AB  - Interprofessional education (IPE) for health and social care students may improve
      attitudes toward IPE and interprofessional collaboration (IPC). The quality of
      research on the association between IPE and attitudes is mediocre and IPE effect
      sizes are unknown. Students at a college in Toronto, Canada, attended an IPE
      workshop. A comparison group of non-attenders was formed. Both groups completed
      pre- and post-workshop questionnaires and two measurement scales for IPE
      attitudes-the Interprofessional Education Perceptions Scale and the University of
      West England questionnaire. Eight multiple linear regressions modeled post
      workshop attitude scores as a function of workshop attendance, pre-workshop
      attitudes, and background factors. Workshop effect sizes and relative importance
      of variables were estimated. Published results were used to calculate IPE effect
      sizes in other studies. Pre-workshop measures of post-workshop attitudes were
      dominant, positive predictors of outcomes; other predictors were subordinate to
      them. The relationship between workshop attendance and IPE attitudes was positive
      in seven models, statistically significant in four (P < 0.05), and not
      statistically significant in four. In hierarchical regressions the average
      workshop effect was small, about 0.08 in DeltaR(2) terms, amounting to about one
      quarter of a model's explained variance. The workshop was associated with
      improved IPE and IPC attitudes in some domains but not others. The results should
      help educators focus IPE efforts on IPE/IPC attitudes where small, short-term
      improvements can be obtained.

PMID- 22160642
TI  - Incremental increase in VEGFR1+ hematopoietic progenitor cells and VEGFR2+
      endothelial progenitor cells predicts relapse and lack of tumor response in
      breast cancer patients.
AB  - Animal models have demonstrated the critical role of bone marrow-derived
      VEGFR1(+) hematopoietic progenitor cells (HPCs) and VEGFR2(+) endothelial
      progenitor cells (EPCs) in metastatic progression. We explored whether these
      cells could predict relapse and response in breast cancer (BC) patients. One
      hundred and thirty-two patients with stages 1-4 BC were enrolled on 2 studies.
      Circulating CD45(+)/CD34(+)/VEGFR1(+) HPCs and CD45(dim)/CD133(+)/VEGFR2(+) EPCs
      were assessed from peripheral blood mononuclear cells using flow cytometry.
      Changes in HPCs and EPCs were analyzed in (1) patients without overt disease that
      relapsed and (2) metastatic patients according to response by RECIST. At study
      entry, 102 patients were without evidence of disease and 30 patients had
      metastatic BC. Seven patients without evidence of BC by exam, labs, and imaging
      developed recurrence while on study. Median HPC/ml (range) increased from 645.8
      (23.5-1,914) to 2,899 (1,176-37,336), P = 0.016, followed by an increase in
      median EPC/ml from 21.3 (4.7-42.5) to 94.7 (28.2-201.3), P = 0.016, prior to
      clinical relapse. In metastatic patients with progressive disease, median HPC/ml
      increased from 1,696 (10-16,470) to 5,124 (374-77,605), P = 0.0009, and median
      EPC/ml increased from 26 (0-560) to 71 (0-615) prior to progression, P = 0.10. In
      patients with responding disease, median HPC/ml decreased from 6,147 (912-85,070)
      to 633 (47-18,065), P = 0.05, and EPC/ml decreased from 46 (0-197) to 23 (0-105),
      P = 0.41, at response. There were no significant changes in these cells over time
      in patients with stable disease. Circulating bone marrow-derived HPCs and EPCs
      predict relapse and disease progression in BC patients.

PMID- 22160645
TI  - Visual preferences for sex and status in female rhesus macaques.
AB  - Most primates are both highly visual and highly social. These qualities predict
      that visual cues to social variables, such as identity, sex, social status, and
      reproductive quality, would be intrinsically valuable and systematically attract
      attention. Supporting this idea, thirsty male rhesus macaques (Macaca mulatta)
      will forego fluid reward to view images of the faces of high-ranking males and
      the sexual skin of females. Whether female rhesus macaques, who experience
      dramatically different social pressures and reproductive costs than male
      macaques, also systematically and spontaneously value visual cues to social
      information remains untested experimentally. We probed the preferences of female
      rhesus macaques, given the opportunity to display an image from a known class of
      social stimuli or touch a second target to display a blank screen. We found that
      females preferred faces of high-status males and also images of the perinea of
      both males and females, but were not motivated to display images of subordinate
      males or control stimuli. These findings endorse the view that both male and
      female rhesus macaques-and presumably other highly social primates-seek
      information about other individuals in a way that matches the adaptive value of
      that information for guiding social behavior.

PMID- 22160646
TI  - Evaluation of advanced glycation end products accumulation, using skin
      autofluorescence, in CKD and dialysis patients.
AB  - PURPOSE: Advanced glycation end products (AGE), biomarkers of metabolic stress,
      are frequently encountered in chronic kidney disease (CKD) patients with
      cardiovascular disease. Our aim was to evaluate tissue accumulation of AGEs in
      CKD patients and possible correlations with traditional and non-traditional
      cardiovascular risk factors. METHODS: Skin AF was measured using AGE Reader in
      310 patients: 157 haemodialysis patients (HD) (mean age 60 years, dialysis
      vintage 29 months, 19.1% diabetic), 102 peritoneal dialysis patients (PD) (mean
      age 56.3 years, dialysis vintage 16 months, 17.6% diabetic), 32 CKD patients
      (mean age 68 years, CKD duration 30 months, 34.4% diabetic) and 19 type 2
      diabetic patients, without renal failure (mean age 59 years and median duration
      of diabetes 36 months). RESULTS: HD patients have higher AGE levels compared to
      PD ones. Dialysis patients have the highest skin AF values compared to CKD
      patients (P < 0.05) and diabetic, without renal impairment, patients (P < 0.01).
      Skin AF levels in patients using ARBs and statins are comparable to those without
      treatment in dialysis group (HD + PD) but significantly different in PD sub-group
      and CKD patients. In dialysis patients, diabetes explains 17% of AGE values
      variance. In PD skin, AF correlates with CKD duration (P < 0.01) and dialysis
      vintage (P < 0.05). Skin AF values were significantly higher in anuric PD
      patients (P < 0.05). In our CKD group, we found no significant association with
      diabetes or GFR. CONCLUSIONS: CKD patients have higher AGE values depending on
      duration (disease, RRT) and GFR (dialysis adequacy and RRF). Other important
      determinants were diabetes and age.

PMID- 22160647
TI  - [Pelvic hydatid cyst: differential diagnosis with a bacterial abscess with
      cutaneous fistula].
AB  - The genus Echinococcus is a worldwide tapeworm with a two host mammalian cycle.
      Among the six described species, Echinococcus granulosus (EG) and Echinococcus
      multilocularis are the most important in respect to their public health
      importance. Infected human, as an intermediate accidental host, presents single
      to several cysts, mainly located in the liver. We are describing the clinical,
      radiological and histological findings of a woman born in Morocco, recently
      arrived in France and presenting a pelvic hydatid cyst. The misknowledge of such
      a diagnosis conducted to initial surgery and thus a risk of further metastasised
      lesions. We are suggesting that any hypoechogenic pelvic lesion in a patient
      originated from a Mediterranean country should be considered as a pelvic
      localization of EG.

PMID- 22160648
TI  - Analysis of dose-volume parameters predicting radiation pneumonitis in patients
      with esophageal cancer treated with 3D-conformal radiation therapy or IMRT.
AB  - PURPOSE: Multimodality therapy for esophageal cancer can cause various kinds of
      treatment-related sequelae, especially pulmonary toxicities. This prospective
      study aims to investigate the clinical and dosimetric parameters predicting lung
      injury in patients undergoing radiation therapy for esophageal cancer. METHODS:
      Forty-five esophageal cancer patients were prospectively analyzed. The pulmonary
      toxicities (or sequelae) were evaluated by comparing chest X-ray films, pulmonary
      function tests and symptoms caused by pulmonary damage before and after
      treatment. All patients were treated with either three-dimensional radiotherapy
      (3DCRT) or with intensity-modulated radiotherapy (IMRT). The planning dose volume
      histogram was used to compute the lung volumes receiving more than 5, 10, 20 and
      30 Gy (V5, V10, V20, V30) and mean lung dose. RESULTS: V20 was larger in the IMRT
      group than in the 3DCRT group (p = 0.002). V20 (>15%) and V30 (>20%) resulted in
      a statistically significant increase in the occurrence of chronic pneumonitis (p
      = 0.03) and acute pneumonitis (p = 0.007), respectively. CONCLUSIONS: The study
      signifies that a larger volume of lung receives lower doses because of multiple
      beam arrangement and a smaller volume of lung receives higher doses because of
      better dose conformity in IMRT plans. Acute pneumonitis correlates more with V30
      values, whereas chronic pneumonitis was predominantly seen in patients with
      higher V20 values.

PMID- 22160649
TI  - Chronological evaluation of liver enhancement in patients with chronic liver
      disease at Gd-EOB-DTPA-enhanced 3-T MR imaging: does liver function correlate
      with enhancement?
AB  - PURPOSE: To investigate the chronological relationship between scan delay and
      liver enhancement for the hepatobiliary phase on Gd-EOB-DTPA-enhanced MRI and
      evaluate the effects of liver function on liver enhancement. MATERIALS AND
      METHODS: Hepatobiliary-phase images were retrospectively evaluated in 125
      patients with chronic liver disease. Hepatobiliary phase images were obtained at
      5, 10, 15, and 20 min after injection. We calculated relative liver enhancement
      (RLE) at t min after injection by dividing the signal intensity (SI) of the liver
      at t min by precontrast SI. We compared RLE values at 5, 10, 15, and 20 min and
      evaluated the detectability of focal hepatic lesions. We analyzed the effect of
      liver function on RLE with the generalized linear model. RESULTS: There was not
      significant difference in RLE and lesion detectability at 15 and 20 min. RLE in
      the Child-Pugh C group was significantly lower than in the Child-Pugh A and B
      groups. The serum albumin level and prothrombin time were significantly
      correlated with the liver enhancement. CONCLUSION: A delay time of 15 min for the
      hepatobiliary phase was thought to be adequate in patients with mild liver
      dysfunction. The serum albumin level and prothrombin time would be predictive of
      liver enhancement in the hepatobiliary phase.

PMID- 22160650
TI  - High dose rate brachytherapy using molds after chemoradiotherapy for oral cavity
      cancer.
AB  - PURPOSE: The aim of this study was to investigate the role of the combined use of
      customized molds and a high dose rate (HDR) remote afterloading brachytherapy
      apparatus with a (192)Ir microsource in the treatment of superficial oral
      carcinomas after chemoradiotherapy. MATERIALS AND METHODS: Nine patients with
      oral squamous cell carcinoma who were treated using this combined technique were
      analyzed retrospectively. The primary sites of the tumors were the mouth floor,
      gingiva, and soft palate. For each patient, a customized mold was fabricated in
      which 2-3 afterloading catheters were placed for the (192)Ir source. Three to
      eight fractions of 3 Gy, 5 mm below the mold surface, were given following
      external radiotherapy of 24-50 Gy/2 Gy combined with chemotherapy (peplomycin or
      taxotere). The total dose of HDR brachytherapy ranged from 9 to 24 Gy. RESULTS:
      The 2-year local control probability was 100% and the 2-year cause-specific
      survival rate was 100%. No serious complications (i.e., ulcer or bone exposure)
      have been observed thus far during the follow-up period of 29-120 months.
      CONCLUSION: HDR brachytherapy using the mold technique after chemoradiotherapy is
      a safe and excellent method for selected early and superficial oral cavity
      cancers.

PMID- 22160651
TI  - Computational study of the Sonogashira cross-coupling reaction in the gas phase
      and in dichloromethane solution.
AB  - The Sonogashira cross-couplig reaction, consisting of oxidative addition, cis
      trans isomerization, transmetalation, and reductive elimination, was
      computationally modeled using the DFT B3LYP/cc-pVDZ method for reaction between
      bromobenzene and phenylacetylene. Palladium diphosphane was used as a catalyst,
      copper(I) bromide as a co-catalyst and trimethylamine as a base. The reaction
      mechanism was studied both in the gas phase and in dichloromethane solution using
      PCM method. The complete catalytic cycle is thermodynamically strongly shifted
      toward products (diphenylacetylene and regenerated palladium catalyst) and is
      exothermic being in accordance with experimental data. The rate-determining step
      is the oxidative addition, since the highest point on the Gibbs energy graph of
      the complete reaction is the transition state of this step. This conclusion is
      also supported by recent experimental data. The computed energy profile suggests
      that the transmetalation step is initiated by the dissociation of neutral ligand,
      while the activation Gibbs energy of this step is 0.1 kcal mol(-1) in the gas
      phase.

PMID- 22160653
TI  - vHoT: a database for predicting interspecies interactions between viral microRNA
      and host genomes.
AB  - Some viruses have been reported to transcribe microRNAs, implying complex
      relationships between the host and the pathogen at the post-transcriptional level
      through microRNAs in virus-infected cells. Although many computational algorithms
      have been developed for microRNA target prediction, few have been designed
      exclusively to find cellular or viral mRNA targets of viral microRNAs in a user
      friendly manner. To address this, we introduce the viral microRNA host target
      (vHoT) database for predicting interspecies interactions between viral microRNA
      and host genomes. vHoT supports target prediction of 271 viral microRNAs from
      human, mouse, rat, rhesus monkey, cow, and virus genomes. vHoT is freely
      available at http://dna.korea.ac.kr/vhot.

PMID- 22160654
TI  - FDG-PET performed concurrently with initial I-131 ablation for differentiated
      thyroid cancer.
AB  - OBJECTIVE: Differentiated thyroid cancers (DTCs) are commonly treated by total
      thyroidectomy followed by I-131 radioiodine ablation to eradicate any residual
      thyroid tissue and to detect any metastatic lesions on post-treatment whole body
      scans (TxWBS). However, some DTCs do not trap iodine, resulting in negative whole
      body scanning. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG
      PET) has proven to be a valuable diagnostic technique for detecting many types of
      malignant tumors and metastases. The purpose of this study was to evaluate FDG
      PET performed concurrently with initial I-131 ablation for its ability to detect
      lymph node metastasis and for its role in the management of DTC patients.
      METHODS: A total of 54 patients (16 males and 38 females; median age = 50 years)
      with histologically proven DTC underwent both FDG-PET and subsequent I-131
      ablation. A dose of 3.7 GBq I-131 was administered to 51 patients, 2.96 GBq was
      administered to 1 patient, and 2.22 GBq was administered to 2 patients. FDG-PET
      or PET/CT was performed 3-4 days prior to ablation. TxWBS was conducted 1 week
      after therapy. FDG-PET scans and TxWBS were interpreted by consensus of 2
      experienced radiologists. Serum thyroglobulin (Tg) levels at 3-6 months after
      ablation were compared between PET-positive and PET-negative patients. RESULTS:
      FDG-PET was positive in 25 sites (thyroid bed: n = 9; cervical lymph nodes: n =
      12; mediastinal lymph nodes: n = 3; and axillary lymph nodes: n = 1) of 18
      patients (33%). Only 5 of 16 lymph nodes (31%) that were PET-positive were also
      positive on TxWBS. The success rate of Tg-negative after ablation was
      significantly lower for patients with PET-positive scans than for those with PET
      negative scans (p = 0.026). CONCLUSIONS: FDG-PET performed concurrently with I
      131 ablation can detect lymph node metastases in which radioiodine does not
      accumulate and may influence the management and treatment options for DTC
      patients.

PMID- 22160652
TI  - Theoretical prediction of the binding free energy for mutants of replication
      protein A.
AB  - The replication protein A (RPA) is a heterotrimeric (70, 32, and 14 kDa
      subunits), single stranded DNA (ssDNA) binding protein required for pivotal
      functions in the cell metabolism, such as chromosomal replication, prevention of
      hairpin formation, DNA repair and recombination, and signaling after DNA damage.
      Studies based on deletions and mutations have identified the high affinity ssDNA
      binding domains in the 70 kDa subunit of RPA, regions A and B. Individually, the
      domain A and B have a low affinity for ssDNA, while tandems composed of AA, AB,
      BB, and BA sequences bind the ssDNA with moderate to high affinity. Single and
      double point mutations on polar residues in the binding domains leads to a
      reduction in affinity of RPA for ssDNA, in particular when two hydrophilic
      residues are involved. In view of these results, we performed a study based on
      molecular dynamics simulation aimed to reproduce the experimental change in
      binding free energy, DeltaDeltaG, of RPA70 mutants to further elucidate the
      nature of the protein-ssDNA interaction. The MM-PB(GB)SA methods implemented in
      Amber10 and the code FoldX were used to estimate the binding free energy. The
      theoretical and experimental DeltaDeltaG values correlate better when the results
      are obtained by MM-PBSA calculated on individual trajectories for each mutant. In
      these conditions, the correlation coefficient between experimental and
      theoretical DeltaDeltaG reaches a value of 0.95 despite the overestimation of the
      energy change by one order of magnitude. The decomposition of the MM-GBSA energy
      per residue allows us to correlate the change of the affinity with the residue
      polarity and energy contribution to the binding. The method revealed reliable
      predictions of the change in the affinity in function of mutations, and can be
      used to identify new mutants with distinct binding properties.

PMID- 22160655
TI  - Assessing the impact of chemotherapy-induced peripheral neurotoxicity on the
      quality of life of cancer patients: the introduction of a new measure.
AB  - PURPOSE: To investigate the impact of chemotherapy-induced neurotoxicity on daily
      activities and quality of life (QoL) of cancer patients. METHODS: QoL of all
      patients visiting the oncological outpatient ward of the Maxima Medical Centre in
      the Netherlands from October 2006 until March 2007 treated with taxanes, vinca
      alkaloids and/or platinum compounds (n = 88) was compared with the QoL of
      patients that did not receive these treatments yet (n = 43). Patient-reported
      neuropathy symptoms were evaluated with the newly developed Chemotherapy Induced
      Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer
      Therapy/Gynaecologic Oncology Group/Neurotoxicity (FACT/GOG-Ntx) questionnaire.
      RESULTS: Patients treated with chemotherapy reported significantly more
      complaints of neuropathy (p < 0.001) and more paresthesias and dysesthesias in
      the upper (p < 0.001; p < 0.01) and lower extremities (p < 0.001) compared to
      those not treated with chemotherapy. They additionally experienced problems with
      fine motor function (e.g., getting (un)dressed, writing, and picking up small
      objects). Moreover, cold-induced paresthesias were frequently reported. Overall,
      patients indicated that their neuropathy had a negative effect on QoL.
      CONCLUSIONS: The newly developed CINQ and the FACT/GOG-Ntx results suggest a
      considerable negative impact of patient-reported neuropathy symptoms on daily
      activities and QoL in cancer patients treated with chemotherapy. However, further
      validation of the CINQ is needed.

PMID- 22160656
TI  - Perceptions of low-income African-American mothers about excessive gestational
      weight gain.
AB  - A rising number of low-income African-American mothers gain more weight in
      pregnancy than is recommended, placing them at risk for poor maternal and fetal
      health outcomes. Little is known about the perceptions of mothers in this
      population that may influence excessive gestational weight gain. In 2010-2011, we
      conducted 4 focus groups with 31 low-income, pregnant African-Americans in
      Philadelphia. Two readers independently coded the focus group transcripts to
      identify recurrent themes. We identified 9 themes around perceptions that
      encouraged or discouraged high gestational weight gain. Mothers attributed high
      weight gain to eating more in pregnancy, which was the result of being hungrier
      and the belief that consuming more calories while pregnant was essential for
      babies' health. Family members, especially participants own mothers, strongly
      reinforced the need to "eat for two" to make a healthy baby. Mothers and their
      families recognized the link between poor fetal outcomes and low weight gains but
      not higher gains, and thus, most had a greater pre-occupation with too little
      food intake and weight gain rather than too much. Having physical symptoms from
      overeating and weight retention after previous pregnancies were factors that
      discouraged higher gains. Overall, low-income African-American mothers had more
      perceptions encouraging high gestational weight gain than discouraging it.
      Interventions to prevent excessive weight gain need to be sensitive to these
      perceptions. Messages that link guideline recommended weight gain to optimal
      infant outcomes and mothers' physical symptoms may be most effective for weight
      control.

PMID- 22160657
TI  - Silver threads.

PMID- 22160658
TI  - The role of self-help voluntary associations for women empowerment and social
      capital: the experience of women's iddirs (burial societies) in Ethiopia.
AB  - Mutual help is essential to the human race to progress to a full humanity.
      Participating in voluntary associations has multiple benefits and makes a bigger
      contribution to resiliency in socio-economically deprived neighborhoods.
      Therefore, the objective of the study is to assess the role of women's iddirs
      (burial societies) in promoting their lives, particularly in terms of their
      social and economic well-being. We employed a quantitative cross-sectional
      survey. The study population from which the survey data were collected was
      members of five women's iddirs'. Majority of them (52.5%) reported that their
      iddirs helped them to a great extent to become more connected with the people in
      their local community and 36.4% reported that their confidence has increased to
      have their own say. Nearly three-fourth (70.3%) of the participants indicated
      that members were willing to help each other. About 71.6% totally agreed that
      participation in iddirs alleviates stress and difficulty when a relative or
      family member dies. Majority of the participants (93.3%) stated that their iddirs
      didn't help them to have access to money. All participants (100%) reported that
      their iddirs don't have explicitly stated credit mechanisms and nearly all
      (94.8%) didn't have any experience of borrowing money from banks. Most study
      participants appeared to appreciate the social benefits of iddirs much higher
      than that of their economic benefits. This suggests that iddirs need to be well
      organized and co-operate with each other and ensuring flexible lending and
      interest payment criteria need to be established logistically to serve the needs
      of the poor members.

PMID- 22160659
TI  - Sociodemographic determinants of leisure participation among elderly in Malaysia.
AB  - Leisure participation has been proven to be beneficial and has a positive link to
      successful ageing. This study aims to explore the sociodemographic determinants
      of leisure participation among the Malaysian elderly. A cross-sectional study was
      conducted among persons aged 60 years and above, purposively selected from eight
      health clinics in the state of Selangor. Leisure participation was measured using
      a validated Leisure Participation Questionnaire specific for Malaysian elderly,
      consisting of 25 activities, categorized into 4 categories, namely recreational
      (physical), cognitive, social and productive. Frequency of such participation was
      measured on a 6-point scale. Its association with sociodemographic variables was
      examined using inferential and regression analysis. 268 participants were
      involved in this study (response rate = 100%). The most common daily leisure
      activities were having conversations while relaxing (78.7%), watching television
      (74.6%) and reading (63.4%). The least frequently done leisure activities were
      from the recreational and cognitive categories. The activities were weakly
      correlated to each other, reflecting the lack of diversity of leisure activities
      among respondents. Education was the main predictor for leisure participation
      among elderly, with higher educational level is associated with high RAS (B =
      1.020, P < 0.05), CAS (B = 1.580, P < 0.05) and SAS (B = 1.276, P < 0.05).
      Education level, marital status and locality were important determinants of
      leisure participation among elderly, with education being the main predictor.
      Further studies exploring the effective method of educating the ageing society
      are recommended.

PMID- 22160660
TI  - Measures of the consumer food store environment: a systematic review of the
      evidence 2000-2011.
AB  - Description of the consumer food environment has proliferated in publication.
      However, there has been a lack of systematic reviews focusing on how the consumer
      food environment is associated with the following: (1) neighborhood
      characteristics; (2) food prices; (3) dietary patterns; and (4) weight status. We
      conducted a systematic review of primary, quantitative, observational studies,
      published in English that conducted an audit of the consumer food environment.
      The literature search included electronic, hand searches, and peer-reviewed from
      2000 to 2011. Fifty six papers met the inclusion criteria. Six studies reported
      stores in low income neighborhoods or high minority neighborhoods had less
      availability of healthy food. While, four studies found there was no difference
      in availability between neighborhoods. The results were also inconsistent for
      differences in food prices, dietary patterns, and weight status. This systematic
      review uncovered several key findings. (1) Systematic measurement of determining
      availability of food within stores and store types is needed; (2) Context is
      relevant for understanding the complexities of the consumer food environment; (3)
      Interventions and longitudinal studies addressing purchasing habits, diet, and
      obesity outcomes are needed; and (4) Influences of price and marketing that may
      be linked with why people purchase certain items.

PMID- 22160661
TI  - Fatigue and quality of life in breast cancer survivors: temporal courses and long
      term pattern.
AB  - INTRODUCTION: Fatigue is a frequent problem during and after cancer treatment. We
      investigated different courses of fatigue from pre-diagnosis, through therapy, to
      long-term survivorship and evaluated potential implications on long-term quality
      of life (QoL). METHODS: Breast cancer patients diagnosed in 2001-2005 were
      recruited in a case-control study in Germany (MARIE). At follow-up in 2009
      (median 5.8 years, MARIEplus), patients self-reported current fatigue and QoL
      status using validated questionnaires (FAQ, EORTC QLQ-C30). In addition,
      survivors retrospectively rated fatigue levels pre-diagnosis, during different
      treatment phases, and 1 year post-surgery. Our analyses included 1,928 disease
      free cancer survivors and comparisons with fatigue and QoL scores from the
      general population. RESULTS: Fatigue levels were substantially increased during
      chemotherapy and radiotherapy. Among patients who received both therapies, 61.4%
      reported higher, 30.0% same, and 8.6% lower fatigue levels during chemotherapy
      compared to radiotherapy. Courses of fatigue varied widely between individuals.
      Survivors with persisting long-term fatigue had significantly and markedly worse
      scores for all QoL functions and symptoms about 6 years post-diagnosis than other
      survivors and compared to the general population. Survivors without substantial
      fatigue post-treatment had QoL scores largely comparable to the general
      population. DISCUSSIONS/CONCLUSION: Chemotherapy appears to have a stronger
      impact on fatigue than radiotherapy. Breast cancer survivors may experience long
      term QoL comparable to the general population, even when suffering from
      substantial fatigue during treatment. Yet, persistent fatigue post-treatment may
      lead to extensive long-term loss in QoL concerning physical, social, cognitive,
      and financial aspects. IMPLICATIONS FOR CANCER SURVIVORS: Fatigue management
      should be obligatory during and post cancer treatment.

PMID- 22160662
TI  - "Weaving balance into life": Development and cultural adaptation of a cancer
      symptom management toolkit for Southwest American Indians.
AB  - INTRODUCTION: Self-management of cancer symptoms has the potential to decrease
      the suffering of cancer survivors while improving their health and quality of
      life. For many racial/ethnic groups, culturally appropriate self-management
      instruction is not readily available. This paper reports on the first symptom
      management toolkit developed for American Indian cancer survivors. METHODS: Part
      of a larger research study, a three-phase project tested a cancer symptom self
      management toolkit to be responsive to the unique learning and communication
      needs of American Indians in the Southwest U.S.A. American Indian cancer
      survivors and family members participated in 13 focus groups to identify cultural
      concepts of cancer and illness beliefs, communication styles, barriers, and
      recommendations for self-management techniques. Sessions were audiotaped and
      transcriptions were coded using grounded theory. RESULTS: Participants expressed
      a need for an overview of cancer, tips on management of common symptoms,
      resources in their communities, and suggestions for how to communicate with
      providers and others. The "Weaving balance into life" toolkit is comprised of a
      self-help guide, resource directory, and video. Preferred presentation style and
      content for the toolkit were pilot tested. DISCUSSION/CONCLUSIONS: American
      Indian survivors favor educational materials that provide information on symptom
      management and are tailored to their culture and beliefs. Suggestions for
      adapting the toolkit materials for other American Indian populations are made.
      IMPLICATIONS FOR CANCER SURVIVORS: Many cancer survivors lack effective self
      management techniques for symptoms, such as pain, fatigue, and depression. The
      toolkit promotes self-management strategies for survivors and provides family
      members/caregivers tangible ways to offer support.

PMID- 22160663
TI  - Application of artificial photoperiod in fish: a factor that increases
      susceptibility to infectious diseases?
AB  - This paper describes and evaluates the mortality associated with the potential
      stressor effect induced by application of artificial photoperiods in rainbow
      trout (Oncorhynchus mykiss). After application of artificial photoperiods, high
      mortalities of trout subjected to this management were recorded (36% in LD 14:10
      and 25% in LD 24:0) as compared to controls (7%). The recorded signology related
      to diseased trout included darkening, lethargy and erratic swimming. Among the
      morphological changes, skin lesions and ulcerative-type necrosis could be
      observed. Blood tests, histopathology and isolation of pathogens identified as
      Flavobacterium psychrophilum, associated with Aeromonas, Pseudomonas and
      Saprolegnia sp., were performed. The application of artificial photoperiods
      suggests that fish may be more susceptible to opportunistic diseases; thus, it is
      advisable to emphasize preventive measures in fish subjected to this management.

PMID- 22160664
TI  - Dietary choline, betaine and lecithin mitigates endosulfan-induced stress in
      Labeo rohita fingerlings.
AB  - A five-week experiment was conducted to delineate stress-mitigating effects of
      three different methyl donors in Labeo rohita fingerlings subjected to endosulfan
      toxicity. Four iso-nitrogenous and iso-caloric feed were prepared with and
      without supplementation of methyl donors. The feed were basal or control diet
      (i.e., without methyl donor supplementation), feed supplemented with choline,
      feed supplemented with betaine and feed supplemented with lecithin. Two hundred
      and twenty-five fishes were distributed randomly in five treatment groups each
      with three replicates. The experimental setup were normal water (without
      endosulfan) and fed with control diet (control group), endosulfan-treated water
      and fed with control diet (T1), endosulfan-treated water and fed with choline
      supplemented feed (T2), endosulfan-treated water and fed with betaine
      supplemented feed (T3) and endosulfan-treated water and fed with lecithin
      supplemented feed (T4). The level of endosulfan in endosulfan treated water was
      maintained at the level of 1/10 of LC50, that is, 0.2 ppb. During the experiment,
      growth performances, metabolic enzyme activity and histological examination were
      done to assess the effect of treatments. The growth performance (percentage
      weight gain, feed conversion ratio, specific growth rate and protein efficiency
      ratio) and nutrient digestibility were significantly different (P<0.01) in
      lecithin, betaine and choline fed group when compared to endosulfan-exposed group
      fed with basal diet. The liver LDH and MDH activity were significantly (P<0.01)
      improved in the groups fed with methyl donor supplemented diet. The liver AST and
      ALT, brain AChE and muscle ALT did not change with supplementation in the diet,
      but muscle ALT and G6PDH significantly (P<0.01) changed with supplementation. The
      gill and liver ATPase and intestinal ALP were significantly (P<0.01) noticeably
      changed in supplemented group. After endosulfan exposure, histopathology alter
      like slight large vacuolation in hepatocyte and lipoid vacuole were observed and
      with supplementation normal appearance of liver were observed. The chromosome
      aberration (karyotype) was observed in endosulfan-exposed group. The result
      obtained in present study concluded that inclusion of methyl donors, particularly
      lecithin and betaine, in feed as nutritional supplements has a potential stress
      mitigating effect in L. rohita fingerlings.

PMID- 22160665
TI  - F10 gene hypomethylation, a putative biomarker for glioma prognosis.
AB  - Tumors are usually characterized by an imbalance in cytosine methylation,
      including hypomethylation of CpG islands. In this study, bisulfite sequencing PCR
      was used to assess the promoter methylation status of coagulation factor X (F10)
      gene in tumors of 96 glioma patients and in glioma cells U251, SF767, and SF126,
      and the effect of promoter hypomethylation on protein expression was evaluated
      immunohistochemically. The study showed that the demethylation ratio of F10 in
      SF126, SF767, and U251 cells was 38.6, 26.4, and 24.3% respectively.
      Hypomethylation of F10 was detected in 82.3% of glioma specimens and in no normal
      brain tissues, with significant correlation with its protein expression. However
      there was no remarkable relationship between F10 hypomethylation and sex, age,
      and advanced tumor grade. The correlation between F10 hypomethylation, protein
      expression, and overall survival (OS) was statistically significant.
      Hypomethylation of F10 promoter in gliomas accounted for F10 encoding protein FX
      overexpression and aggressive biological behavior in a subset of patients.
      Furthermore, in the F10 hypomethylation group, OS was shorter for patients with
      F10 overexpression than for those without. Detection of these epigenetic changes
      in tumors may provide important information regarding prognosis.

PMID- 22160666
TI  - Automated quantification of carotid artery stenosis on contrast-enhanced MRA data
      using a deformable vascular tube model.
AB  - The purpose of this study was to develop and validate a method for automated
      segmentation of the carotid artery lumen from volumetric MR Angiographic (MRA)
      images using a deformable tubular 3D Non-Uniform Rational B-Splines (NURBS)
      model. A flexible 3D tubular NURBS model was designed to delineate the carotid
      arterial lumen. User interaction was allowed to guide the model by placement of
      forbidden areas. Contrast-enhanced MRA (CE-MRA) from 21 patients with carotid
      atherosclerotic disease were included in this study. The validation was performed
      against expert drawn contours on multi-planar reformatted image slices
      perpendicular to the artery. Excellent linear correlations were found on cross
      sectional area measurement (r = 0.98, P < 0.05) and on luminal diameter (r =
      0.98, P < 0.05). Strong match in terms of the Dice similarity indices were
      achieved: 0.95 +/- 0.02 (common carotid artery), 0.90 +/- 0.07 (internal carotid
      artery), 0.87 +/- 0.07 (external carotid artery), 0.88 +/- 0.09 (carotid
      bifurcation) and 0.75 +/- 0.20 (stenosed segments). Slight overestimation of
      stenosis grading by the automated method was observed. The mean differences was
      7.20% (SD = 21.00%) and 5.2% (SD = 21.96%) when validated against two observers.
      Reproducibility in stenosis grade calculation by the automated method was high;
      the mean difference between two repeated analyses was 1.9 +/- 7.3%. In
      conclusion, the automated method shows high potential for clinical application in
      the analysis of CE-MRA of carotid arteries.

PMID- 22160667
TI  - Characterization of the failing murine heart in a desmin knock-out model using a
      clinical 3 T MRI scanner.
AB  - The purpose of this study was to establish an MRI protocol on a clinical scanner
      for assessment of left (LV) and right (RV) ventricular myocardial function of the
      murine heart, and to apply this protocol for the first in vivo assessment of
      myocardial function in a mouse model of cardiomyopathy (Desmin-/-). MRI was
      performed on a clinical 3 T whole body MRI system using a dedicated solenoid
      receive-only coil. Contiguous short axis slices were acquired covering the entire
      heart using a spoiled cine gradient echo sequence (TR 9-12 ms, TE 3-4 ms, alpha
      25 degrees , 1.0 * 0.23 * 0.23 mm3). Global LV- and RV-myocardial functional
      parameters such as end-diastolic ventricular volume, ejection fraction (EF), LV
      mass and cardiac output (CO) of Desmin-/- mice and age-matched controls were
      determined. Global myocardial functional data of healthy controls (n = 4) were in
      very good agreement with previously reported data. The transgenic mice (n = 8)
      revealed a significantly reduced LV- and RV-EF as well as CO. Body weight
      normalized LV- and RV-end-diastolic volumes and LV mass were significantly
      increased. In addition desmin deficient mice exhibited segmental wall thinning
      and akinesia, suggesting myocardial necrosis. This study demonstrates that
      clinical 3 T MRI-systems may reliably be used for non-invasive assessment of LV-
      and RV-myocardial function in normal and in genetically engineered mice with
      cardiomyopathies. In addition, this proof of principle study presents first in
      vivo MRI data of the cardiac phenotype of desmin knock-out mice.

PMID- 22160668
TI  - New automated Markov-Gibbs random field based framework for myocardial wall
      viability quantification on agent enhanced cardiac magnetic resonance images.
AB  - A novel automated framework for detecting and quantifying viability from agent
      enhanced cardiac magnetic resonance images is proposed. The framework identifies
      the pathological tissues based on a joint Markov-Gibbs random field (MGRF) model
      that accounts for the 1st-order visual appearance of the myocardial wall (in
      terms of the pixel-wise intensities) and the 2nd-order spatial interactions
      between pixels. The pathological tissue is quantified based on two metrics: the
      percentage area in each segment with respect to the total area of the segment,
      and the trans-wall extent of the pathological tissue. This transmural extent is
      estimated using point-to-point correspondences based on a Laplace partial
      differential equation. Transmural extent was validated using a simulated phantom.
      We tested the proposed framework on 14 datasets (168 images) and validated
      against manual expert delineation of the pathological tissue by two observers.
      Mean Dice similarity coefficients (DSC) of 0.90 and 0.88 were obtained for the
      observers, approaching the ideal value, 1. The Bland-Altman statistic of infarct
      volumes estimated by manual versus the MGRF estimation revealed little bias
      difference, and most values fell within the 95% confidence interval, suggesting
      very good agreement. Using the DSC measure we documented statistically
      significant superior segmentation performance for our MGRF method versus
      established intensity-based methods (greater DSC, and smaller standard
      deviation). Our Laplace method showed good operating characteristics across the
      full range of extent of transmural infarct, outperforming conventional methods.
      Phantom validation and experiments on patient data confirmed the robustness and
      accuracy of the proposed framework.

PMID- 22160669
TI  - "Fatal" gas in the kidney.

PMID- 22160670
TI  - High plasma pentosidine level is accompanied with cardiovascular events in
      hemodialysis patients.
AB  - BACKGROUND: Cardiovascular disease is a major complication in patients with end
      stage renal disease (ESRD). The accumulation of advanced glycation end products
      (AGEs) is facilitated in these patients. The aim of this study was to investigate
      the relationship between circulating AGEs and cardiovascular events in
      hemodialysis patients. METHODS: The plasma level of pentosidine, a well-defined
      AGEs, was measured in 110 hemodialysis patients who were prospectively followed
      for 90 months. The relationship between plasma pentosidine level and
      cardiovascular events was assessed using Kaplan-Meier and Cox regression
      analysis. RESULTS: Thirty-nine cardiovascular events (14 coronary heart disease
      and 25 strokes) occurred during the follow-up period. Multivariable Cox
      proportional hazard analysis showed that plasma pentosidine levels (HR 1.040, 95%
      CI 1.022-1.058, p < 0.01) were correlated to increased risk for cardiovascular
      events. When patients were divided into four groups according to plasma
      pentosidine levels, Kaplan-Meier analysis revealed that cardiovascular events in
      the highest pentosidine group were significantly greater than in the other groups
      (p < 0.01 in lower and low, and p < 0.05 in high pentosidine groups). CONCLUSION:
      The plasma pentosidine level predicts cardiovascular events in hemodialysis
      patients. The effects of lowering circulating AGE levels on cardiovascular events
      should be examined in ESRD patients.

PMID- 22160671
TI  - Structural interconversions modulate activity of Escherichia coli ribonucleotide
      reductase.
AB  - Essential for DNA biosynthesis and repair, ribonucleotide reductases (RNRs)
      convert ribonucleotides to deoxyribonucleotides via radical-based chemistry.
      Although long known that allosteric regulation of RNR activity is vital for cell
      health, the molecular basis of this regulation has been enigmatic, largely due to
      a lack of structural information about how the catalytic subunit (alpha(2)) and
      the radical-generation subunit (beta(2)) interact. Here we present the first
      structure of a complex between alpha(2) and beta(2) subunits for the prototypic
      RNR from Escherichia coli. Using four techniques (small-angle X-ray scattering, X
      ray crystallography, electron microscopy, and analytical ultracentrifugation), we
      describe an unprecedented alpha(4)beta(4) ring-like structure in the presence of
      the negative activity effector dATP and provide structural support for an active
      alpha(2)beta(2) configuration. We demonstrate that, under physiological
      conditions, E. coli RNR exists as a mixture of transient alpha(2)beta(2) and
      alpha(4)beta(4) species whose distributions are modulated by allosteric
      effectors. We further show that this interconversion between alpha(2)beta(2) and
      alpha(4)beta(4) entails dramatic subunit rearrangements, providing a stunning
      molecular explanation for the allosteric regulation of RNR activity in E. coli.

PMID- 22160672
TI  - Self-assembly of soft-matter quasicrystals and their approximants.
AB  - The surprising recent discoveries of quasicrystals and their approximants in soft
      matter systems poses the intriguing possibility that these structures can be
      realized in a broad range of nanoscale and microscale assemblies. It has been
      theorized that soft-matter quasicrystals and approximants are largely
      entropically stabilized, but the thermodynamic mechanism underlying their
      formation remains elusive. Here, we use computer simulation and free-energy
      calculations to demonstrate a simple design heuristic for assembling
      quasicrystals and approximants in soft-matter systems. Our study builds on
      previous simulation studies of the self-assembly of dodecagonal quasicrystals and
      approximants in minimal systems of spherical particles with complex, highly
      specific interaction potentials. We demonstrate an alternative entropy-based
      approach for assembling dodecagonal quasicrystals and approximants based solely
      on particle functionalization and shape, thereby recasting the interaction
      potential-based assembly strategy in terms of simpler-to-achieve bonded and
      excluded-volume interactions. Here, spherical building blocks are functionalized
      with mobile surface entities to encourage the formation of structures with low
      surface contact area, including non-close-packed and polytetrahedral structures.
      The building blocks also possess shape polydispersity, where a subset of the
      building blocks deviate from the ideal spherical shape, discouraging the
      formation of close-packed crystals. We show that three different model systems
      with both of these features-mobile surface entities and shape polydispersity
      consistently assemble quasicrystals and/or approximants. We argue that this
      design strategy can be widely exploited to assemble quasicrystals and
      approximants on the nanoscale and microscale. In addition, our results further
      elucidate the formation of soft-matter quasicrystals in experiment.

PMID- 22160673
TI  - Large-area optoelastic manipulation of colloidal particles in liquid crystals
      using photoresponsive molecular surface monolayers.
AB  - Noncontact optical trapping and manipulation of micrometer- and nanometer-sized
      particles are typically achieved by use of forces and torques exerted by tightly
      focused high-intensity laser beams. Although they were instrumental for many
      scientific breakthroughs, these approaches find few technological applications
      mainly because of the small-area manipulation capabilities, the need for using
      high laser powers, limited application to anisotropic fluids and low-refractive
      index particles, as well as complexity of implementation. To overcome these
      limitations, recent research efforts have been directed toward extending the
      scope of noncontact optical control through the use of optically-guided
      electrokinetic forces, vortex laser beams, plasmonics, and optofluidics. Here we
      demonstrate manipulation of colloidal particles and self-assembled structures in
      nematic liquid crystals by means of single-molecule-thick, light-controlled
      surface monolayers. Using polarized light of intensity from 1,000 to 100,000
      times smaller than that in conventional optical tweezers, we rotate, translate,
      localize, and assemble spherical and complex-shaped particles of various sizes
      and compositions. By controlling boundary conditions through the monolayer, we
      manipulate the liquid crystal director field and the landscape of ensuing elastic
      forces exerted on colloids by the host medium. This permits the centimeter-scale,
      massively parallel manipulation of particles and complex colloidal structures
      that can be dynamically controlled by changing illumination or assembled into
      stationary stable configurations dictated by the "memorized" optoelastic
      potential landscape due to the last illumination pattern. We characterize the
      strength of optically guided elastic forces and discuss the potential uses of
      this noncontact manipulation in fabrication of novel optically- and electrically
      tunable composites from liquid crystals and colloids.

PMID- 22160674
TI  - Imaging protein synthesis in cells and tissues with an alkyne analog of
      puromycin.
AB  - Synthesis of many proteins is tightly controlled at the level of translation, and
      plays an essential role in fundamental processes such as cell growth and
      proliferation, signaling, differentiation, or death. Methods that allow imaging
      and identification of nascent proteins are critical for dissecting regulation of
      translation, both spatially and temporally, particularly in whole organisms. We
      introduce a simple and robust chemical method to image and affinity-purify
      nascent proteins in cells and in animals, based on an alkyne analog of puromycin,
      O-propargyl-puromycin (OP-puro). OP-puro forms covalent conjugates with nascent
      polypeptide chains, which are rapidly turned over by the proteasome and can be
      visualized or captured by copper(I)-catalyzed azide-alkyne cycloaddition. Unlike
      methionine analogs, OP-puro does not require methionine-free conditions and,
      uniquely, can be used to label and assay nascent proteins in whole organisms.
      This strategy should have broad applicability for imaging protein synthesis and
      for identifying proteins synthesized under various physiological and pathological
      conditions in vivo.

PMID- 22160675
TI  - Chemoresponsive alternating supramolecular copolymers created from
      heterocomplementary calix[4]pyrroles.
AB  - The importance of noncovalent interactions in the realm of biological materials
      continues to inspire efforts to create artificial supramolecular polymeric
      architectures. These types of self-assembled materials hold great promise as
      environmentally stimuli-responsive materials because they are capable of
      adjusting their various structural parameters, such as chain length,
      architecture, conformation, and dynamics, to new surrounding environments upon
      exposure to appropriate external stimuli. Nevertheless, in spite of considerable
      advances in the area of responsive materials, it has proved challenging to create
      synthetic self-assembled materials that respond to highly disparate analytes and
      whose environmentally induced changes in structure can be followed directly
      through both various spectroscopic and X-ray diffraction analyses. Herein, we
      report a new set of artificial self-assembled materials obtained by simply mixing
      two appropriately chosen, heterocomplementary macrocyclic receptors, namely a
      tetrathiafulvalene-functionalized calix[4]pyrrole and a bis(dinitrophenyl)-meso
      substituted calix[4]pyrrole. The resulting polymeric materials, stabilized by
      combination of donor-acceptor and hydrogen bonding interactions, undergo dynamic,
      reversible dual guest-dependent structural transformations upon exposure to two
      very different types of external chemical inputs, namely chloride anion and
      trinitrobenzene. The structure and dynamics of the copolymers and their analyte
      dependent responsive behavior was established via single crystal X-ray
      crystallography, SEM, heterocomplementary isodesmic analysis, 1- and 2D NMR, and
      dynamic light scattering spectroscopies. Our results demonstrate the benefit of
      using designed heterocomplementary interactions of two functional macrocyclic
      receptors to create synthetic, self-assembled materials for the development of
      "smart" sensory materials that mimic the key biological attributes of
      multianalyte recognition and substrate-dependent multisignaling.

PMID- 22160676
TI  - Cumulative impacts of mountaintop mining on an Appalachian watershed.
AB  - Mountaintop mining is the dominant form of coal mining and the largest driver of
      land cover change in the central Appalachians. The waste rock from these surface
      mines is disposed of in the adjacent river valleys, leading to a burial of
      headwater streams and dramatic increases in salinity and trace metal
      concentrations immediately downstream. In this synoptic study we document the
      cumulative impact of more than 100 mining discharge outlets and approximately 28
      km(2) of active and reclaimed surface coal mines on the Upper Mud River of West
      Virginia. We measured the concentrations of major and trace elements within the
      tributaries and the mainstem and found that upstream of the mines water quality
      was equivalent to state reference sites. However, as eight separate mining
      impacted tributaries contributed their flow, conductivity and the concentrations
      of selenium, sulfate, magnesium, and other inorganic solutes increased at a rate
      directly proportional to the upstream areal extent of mining. We found strong
      linear correlations between the concentrations of these contaminants in the river
      and the proportion of the contributing watershed in surface mines. All
      tributaries draining mountaintop-mining-impacted catchments were characterized by
      high conductivity and increased sulfate concentration, while concentrations of
      some solutes such as Se, Sr, and N were lower in the two tributaries draining
      reclaimed mines. Our results demonstrate the cumulative impact of multiple mines
      within a single catchment and provide evidence that mines reclaimed nearly two
      decades ago continue to contribute significantly to water quality degradation
      within this watershed.

PMID- 22160677
TI  - Ultrahydrous stishovite from high-pressure hydrothermal treatment of SiO2.
AB  - Stishovite (SiO(2) with the rutile structure and octahedrally coordinated
      silicon) is an important high-pressure mineral. It has previously been considered
      to be essentially anhydrous. In this study, hydrothermal treatment of silica
      glass and coesite at 350-550  degrees C near 10 GPa produces stishovite with
      significant amounts of H(2)O in its structure. A combination of methodologies (X
      ray diffraction, thermal analysis, oxide melt solution calorimetry, secondary ion
      mass spectrometry, infrared and nuclear magnetic resonance spectroscopy) indicate
      the presence of 1.3 +/- 0.2 wt % H(2)O and NMR suggests that the primary
      mechanism for the H(2)O uptake is a direct hydrogarnet-like substitution of 4H(+)
      for Si(4+), with the protons clustered as hydroxyls around a silicon vacancy.
      This substitution is accompanied by a substantial volume decrease for the system
      (SiO(2) + H(2)O), although the stishovite expands slightly, and it is only
      slightly unfavorable in energy. Stishovite could thus be a host for H(2)O at
      convergent plate boundaries, and in other relatively cool high-pressure
      environments.

PMID- 22160678
TI  - Role of structurally and magnetically modified nanoclusters in colossal
      magnetoresistance.
AB  - It is generally accepted that electronic and magnetic phase separation is the
      origin of many of exotic properties of strongly correlated electron materials,
      such as colossal magnetoresistance (CMR), an unusually large variation in the
      electrical resistivity under applied magnetic field. In the simplest picture, the
      two competing phases are those associated with the material state on either side
      of the phase transition. Those phases would be paramagnetic insulator and
      ferromagnetic metal for the CMR effect in doped manganites. It has been
      speculated that a critical component of the CMR phenomenon is nanoclusters with
      quite different properties than either of the terminal phases during the
      transition. However, the role of these nanoclusters in the CMR effect remains
      elusive because the physical properties of the nanoclusters are hard to measure
      when embedded in bulk materials. Here we show the unexpected behavior of the
      nanoclusters in the CMR compound La(1-x)Ca(x)MnO(3) (0.4 <= x < 0.5) by directly
      correlating transmission electron microscopy observations with bulk measurements.
      The structurally modified nanoclusters at the CMR temperature were found to be
      ferromagnetic and exhibit much higher electrical conductivity than previously
      proposed. Only at temperatures much below the CMR transition, the nanoclusters
      are antiferromagnetic and insulating. These findings substantially alter the
      current understanding of these nanoclusters on the material's functionality and
      would shed light on the microscopic study on the competing spin-lattice-charge
      orders in strongly correlated systems.

PMID- 22160679
TI  - Solar hydrogen-producing bionanodevice outperforms natural photosynthesis.
AB  - Although a number of solar biohydrogen systems employing photosystem I (PSI) have
      been developed, few attain the electron transfer throughput of oxygenic
      photosynthesis. We have optimized a biological/organic nanoconstruct that
      directly tethers F(B), the terminal [4Fe-4S] cluster of PSI from Synechococcus
      sp. PCC 7002, to the distal [4Fe-4S] cluster of the [FeFe]-hydrogenase (H(2)ase)
      from Clostridium acetobutylicum. On illumination, the PSI-[FeFe]-H(2)ase
      nanoconstruct evolves H(2) at a rate of 2,200 +/- 460 MUmol mg chlorophyll(-1) h(
      1), which is equivalent to 105 +/- 22 e(-)PSI(-1) s(-1). Cyanobacteria evolve
      O(2) at a rate of approximately 400 MUmol mg chlorophyll(-1) h(-1), which is
      equivalent to 47 e(-)PSI(-1) s(-1), given a PSI to photosystem II ratio of 1.8.
      The greater than twofold electron throughput by this hybrid biological/organic
      nanoconstruct over in vivo oxygenic photosynthesis validates the concept of
      tethering proteins through their redox cofactors to overcome diffusion-based rate
      limitations on electron transfer.

PMID- 22160680
TI  - Conformational plasticity of glycogenin and its maltosaccharide substrate during
      glycogen biogenesis.
AB  - Glycogenin initiates the synthesis of a maltosaccharide chain covalently attached
      to itself on Tyr195 via a stepwise glucosylation reaction, priming glycogen
      synthesis. We have captured crystallographic snapshots of human glycogenin during
      its reaction cycle, revealing a dynamic conformational switch between ground and
      active states mediated by the sugar donor UDP-glucose. This switch includes the
      ordering of a polypeptide stretch containing Tyr195, and major movement of an
      approximately 30-residue "lid" segment covering the active site. The rearranged
      lid guides the nascent maltosaccharide chain into the active site in either an
      intra- or intersubunit mode dependent upon chain length and steric factors and
      positions the donor and acceptor sugar groups for catalysis. The Thr83Met
      mutation, which causes glycogen storage disease XV, is conformationally locked in
      the ground state and catalytically inactive. Our data highlight the
      conformational plasticity of glycogenin and coexistence of two modes of
      glucosylation as integral to its catalytic mechanism.

PMID- 22160681
TI  - Proton-coupled electron transfer at modified electrodes by multiple pathways.
AB  - In single site water or hydrocarbon oxidation catalysis with polypyridyl Ru
      complexes such as [Ru(II)(Mebimpy)(bpy)(H(2)O)](2+) [where bpy is 2,2'
      bipyridine, and Mebimpy is 2,6-bis(1-methylbenzimidazol-2-yl)pyridine] 2, or its
      surface-bound analog [Ru(II)(Mebimpy)(4,4'-bis-methlylenephosphonato-2,2'
      bipyridine)(OH(2))](2+) 2-PO(3)H(2), accessing the reactive states, Ru(V) =
      O(3+)/Ru(IV) = O(2+), at the electrode interface is typically rate limiting. The
      higher oxidation states are accessible by proton-coupled electron transfer
      oxidation of aqua precursors, but access at inert electrodes is kinetically
      inhibited. The inhibition arises from stepwise mechanisms which impose high
      energy barriers for 1e- intermediates. Oxidation of the Ru(III)-OH(2+) or forms
      of 2-PO(3)H(2) to Ru(IV) = O(2+) on planar fluoride-doped SnO(2) electrode and in
      nanostructured films of Sn(IV)-doped In(2)O(3) and TiO(2) has been investigated
      with a focus on identifying microscopic phenomena. The results provide direct
      evidence for important roles for the nature of the electrode, temperature,
      surface coverage, added buffer base, pH, solvent, and solvent H(2)O/D(2)O isotope
      effects. In the nonaqueous solvent, propylene carbonate, there is evidence for a
      role for surface-bound phosphonate groups as proton acceptors.

PMID- 22160682
TI  - Experimental free energy surfaces reveal the mechanisms of maintenance of protein
      solubility.
AB  - The identification of the factors that enable normally folded proteins to remain
      in their soluble and functional states is crucial for a comprehensive
      understanding of any biological system. We have determined a series of energy
      landscapes of the acylphosphatase from Drosophila melanogaster under a variety of
      conditions by combining NMR measurements with restrained molecular dynamics
      simulations. We thus analyzed the differences in the structures, dynamics, and
      energy surfaces of the protein in its soluble state or in situations where it
      aggregates through conformational states that have native-like structure, folding
      stability, and enzymatic activity. The study identifies the nature of the energy
      barriers that under normal physiological conditions prevent the protein ensemble
      from populating dangerous aggregation-prone states. We found that such states,
      although similar to the native conformation, have altered surface charge
      distribution, alternative topologies of the beta-sheet region, and modified
      solvent exposure of hydrophobic surfaces and aggregation-prone regions of the
      sequence. The identified barriers allow the protein to undergo functional
      dynamics while remaining soluble and without a significant risk of misfolding and
      aggregation into nonfunctional and potentially toxic species.

PMID- 22160683
TI  - Nonlinear structured-illumination microscopy with a photoswitchable protein
      reveals cellular structures at 50-nm resolution.
AB  - Using ultralow light intensities that are well suited for investigating
      biological samples, we demonstrate whole-cell superresolution imaging by
      nonlinear structured-illumination microscopy. Structured-illumination microscopy
      can increase the spatial resolution of a wide-field light microscope by a factor
      of two, with greater resolution extension possible if the emission rate of the
      sample responds nonlinearly to the illumination intensity. Saturating the
      fluorophore excited state is one such nonlinear response, and a realization of
      this idea, saturated structured-illumination microscopy, has achieved
      approximately 50-nm resolution on dye-filled polystyrene beads. Unfortunately,
      because saturation requires extremely high light intensities that are likely to
      accelerate photobleaching and damage even fixed tissue, this implementation is of
      limited use for studying biological samples. Here, reversible photoswitching of a
      fluorescent protein provides the required nonlinearity at light intensities six
      orders of magnitude lower than those needed for saturation. We experimentally
      demonstrate approximately 40-nm resolution on purified microtubules labeled with
      the fluorescent photoswitchable protein Dronpa, and we visualize cellular
      structures by imaging the mammalian nuclear pore and actin cytoskeleton. As a
      result, nonlinear structured-illumination microscopy is now a biologically
      compatible superresolution imaging method.

PMID- 22160684
TI  - A macrocyclic HCV NS3/4A protease inhibitor interacts with protease and helicase
      residues in the complex with its full-length target.
AB  - Hepatitis C virus (HCV) infection is a global health burden with over 170 million
      people infected worldwide. In a significant portion of patients chronic hepatitis
      C infection leads to serious liver diseases, including fibrosis, cirrhosis, and
      hepatocellular carcinoma. The HCV NS3 protein is essential for viral polyprotein
      processing and RNA replication and hence viral replication. It is composed of an
      N-terminal serine protease domain and a C-terminal helicase/NTPase domain. For
      full activity, the protease requires the NS4A protein as a cofactor. HCV NS3/4A
      protease is a prime target for developing direct-acting antiviral agents. First
      generation NS3/4A protease inhibitors have recently been introduced into clinical
      practice, markedly changing HCV treatment options. To date, crystal structures of
      HCV NS3/4A protease inhibitors have only been reported in complex with the
      protease domain alone. Here, we present a unique structure of an inhibitor bound
      to the full-length, bifunctional protease-helicase NS3/4A and show that parts of
      the P4 capping and P2 moieties of the inhibitor interact with both protease and
      helicase residues. The structure sheds light on inhibitor binding to the more
      physiologically relevant form of the enzyme and supports exploring inhibitor
      helicase interactions in the design of the next generation of HCV NS3/4A protease
      inhibitors. In addition, small angle X-ray scattering confirmed the observed
      protease-helicase domain assembly in solution.

PMID- 22160685
TI  - Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA
      recognition.
AB  - MDA5, an RIG-I-like helicase, is a conserved cytoplasmic viral RNA sensor, which
      recognizes dsRNA from a wide-range of viruses in a length-dependent manner. It
      has been proposed that MDA5 forms higher-order structures upon viral dsRNA
      recognition or during antiviral signaling, however the organization and nature of
      this proposed oligomeric state is unknown. We report here that MDA5 cooperatively
      assembles into a filamentous oligomer composed of a repeating segmental
      arrangement of MDA5 dimers along the length of dsRNA. Binding of MDA5 to dsRNA
      stimulates its ATP hydrolysis activity with little coordination between
      neighboring molecules within a filament. Individual ATP hydrolysis in turn
      renders an intrinsic kinetic instability to the MDA5 filament, triggering
      dissociation of MDA5 from dsRNA at a rate inversely proportional to the filament
      length. These results suggest a previously unrecognized role of ATP hydrolysis in
      control of filament assembly and disassembly processes, thereby autoregulating
      the interaction of MDA5 with dsRNA, and provides a potential basis for dsRNA
      length-dependent antiviral signaling.

PMID- 22160686
TI  - Inhibition of eye blinking reveals subjective perceptions of stimulus salience.
AB  - Spontaneous eye blinking serves a critical physiological function, but it also
      interrupts incoming visual information. This tradeoff suggests that the
      inhibition of eye blinks might constitute an adaptive reaction to minimize the
      loss of visual information, particularly information that a viewer perceives to
      be important. To test this hypothesis, we examined whether the timing of blink
      inhibition, during natural viewing, is modulated between as well as within tasks,
      and also whether the timing of blink inhibition varies as a function of viewer
      engagement and stimulus event type. While viewing video scenes, we measured the
      timing of blinks and blink inhibition, as well as visual scanning, in a group of
      typical two-year-olds, and in a group of two-year-olds known for attenuated
      reactivity to affective stimuli: toddlers with Autism Spectrum Disorders (ASD).
      Although both groups dynamically adjusted the timing of their blink inhibition at
      levels greater than expected by chance, they inhibited their blinking and shifted
      visual fixation differentially with respect to salient onscreen events. Moreover,
      typical toddlers inhibited their blinking earlier than toddlers with ASD,
      indicating active anticipation of the unfolding of those events. These findings
      indicate that measures of blink inhibition can serve as temporally precise
      markers of perceived stimulus salience and are useful quantifiers of atypical
      processing of social affective signals in toddlers with ASD.

PMID- 22160687
TI  - Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of
      synaptic protein targets.
AB  - The p53-family member TAp73 is a transcription factor that plays a key role in
      many biological processes. Here, we show that p73 drives the expression of
      microRNA (miR)-34a, but not miR-34b and -c, by acting on specific binding sites
      on the miR-34a promoter. Expression of miR-34a is modulated in parallel with that
      of TAp73 during in vitro differentiation of neuroblastoma cells and cortical
      neurons. Retinoid-driven neuroblastoma differentiation is inhibited by knockdown
      of either p73 or miR-34a. Transcript expression of miR-34a is significantly
      reduced in vivo both in the cortex and hippocampus of p73(-/-) mice; miR-34a and
      TAp73 expression also increase during postnatal development of the brain and
      cerebellum when synaptogenesis occurs. Accordingly, overexpression or silencing
      of miR-34a inversely modulates expression of synaptic targets, including
      synaptotagmin-1 and syntaxin-1A. Notably, the axis TAp73/miR-34a/synaptotagmin-1
      is conserved in brains from Alzheimer's patients. These data reinforce a role for
      TAp73 in neuronal development.

PMID- 22160688
TI  - Behavioral evidence for the evolution of walking and bounding before
      terrestriality in sarcopterygian fishes.
AB  - Tetrapods evolved from sarcopterygian fishes in the Devonian and were the first
      vertebrates to colonize land. The locomotor component of this transition can be
      divided into four major events: terrestriality, the origins of digited limbs,
      solid substrate-based locomotion, and alternating gaits that use pelvic
      appendages as major propulsors. As the sister group to tetrapods, lungfish are a
      morphologically and phylogenetically relevant sarcopterygian taxon for
      understanding the order in which these events occurred. We found that a species
      of African lungfish (Protopterus annectens) uses a range of pelvic fin-driven,
      tetrapod-like gaits, including walking and bounding, in an aquatic environment,
      despite having a derived limb endoskeleton and primitively small, muscularly
      supported pelvis. Surprisingly, given these morphological traits, P. annectens
      also lifts its body clear of the substrate using its pelvic fins, an ability
      thought to be a tetrapod innovation. Our findings suggest that some fundamental
      features of tetrapod locomotion, including pelvic limb gait patterns and
      substrate association, probably arose in sarcopterygians before the origin of
      digited limbs or terrestriality. It follows that the attribution of some of the
      nondigited Devonian fossil trackways to limbed tetrapods may need to be
      revisited.

PMID- 22160689
TI  - High salt and DNA double-strand breaks.

PMID- 22160690
TI  - Antagonistic gene transcripts regulate adaptation to new growth environments.
AB  - Cells have evolved complex regulatory networks that reorganize gene expression
      patterns in response to changing environmental conditions. These changes often
      involve redundant mechanisms that affect various levels of gene expression. Here,
      we examine the consequences of enhanced mRNA degradation in the galactose
      utilization network of Saccharomyces cerevisiae. We observe that glucose-induced
      degradation of GAL1 transcripts provides a transient growth advantage to cells
      upon addition of glucose. We show that the advantage arises from relief of
      translational competition between GAL1 transcripts and those of cyclin CLN3, a
      translationally regulated initiator of cell division. This competition creates a
      translational bottleneck that balances the production of Gal1p and Cln3p and
      represents a posttranscriptional control mechanism that enhances the cell's
      ability to adapt to changes in carbon source. We present evidence that the
      spatial regulation of GAL1 and CLN3 transcripts is what allows growth to be
      maintained during fluctuations of glucose availability. Our results provide
      unique insights into how cells optimize energy use during growth in a dynamic
      environment.

PMID- 22160691
TI  - Systematic control of protein interactions for systems biology.

PMID- 22160692
TI  - Polyfunctional responses by human T cells result from sequential release of
      cytokines.
AB  - The release of cytokines by T cells defines a significant part of their
      functional activity in vivo, and their ability to produce multiple cytokines has
      been associated with beneficial immune responses. To date, time-integrated end
      point measurements have obscured whether these polyfunctional states arise from
      the simultaneous or successive release of cytokines. Here, we used serial, time
      dependent, single-cell analysis of primary human T cells to resolve the temporal
      dynamics of cytokine secretion from individual cells after activation ex vivo. We
      show that multifunctional, Th1-skewed cytokine responses (IFN-gamma, IL-2,
      TNFalpha) are initiated asynchronously, but the ensuing dynamic trajectories of
      these responses evolve programmatically in a sequential manner. That is, cells
      predominantly release one of these cytokines at a time rather than maintain
      active secretion of multiple cytokines simultaneously. Furthermore, these dynamic
      trajectories are strongly associated with the various states of cell
      differentiation suggesting that transient programmatic activities of many
      individual T cells contribute to sustained, population-level responses. The
      trajectories of responses by single cells may also provide unique, time-dependent
      signatures for immune monitoring that are less compromised by the timing and
      duration of integrated measures.

PMID- 22160693
TI  - Imaging dynamic insulin release using a fluorescent zinc indicator for monitoring
      induced exocytotic release (ZIMIR).
AB  - Current methods of monitoring insulin secretion lack the required spatial and
      temporal resolution to adequately map the dynamics of exocytosis of native
      insulin granules in intact cell populations in three dimensions. Exploiting the
      fact that insulin granules contain a high level of Zn(2+), and that Zn(2+) is
      coreleased with insulin during secretion, we have developed a fluorescent, cell
      surface-targeted zinc indicator for monitoring induced exocytotic release
      (ZIMIR). ZIMIR displayed a robust fluorescence enhancement on Zn(2+) chelation
      and bound Zn(2+) with high selectivity against Ca(2+) and Mg(2+). When added to
      cultured beta cells or intact pancreatic islets at low micromolar concentrations,
      ZIMIR labeled cells rapidly, noninvasively, and stably, and it reliably reported
      changes in Zn(2+) concentration near the sites of granule fusion with high
      sensitivity that correlated well with membrane capacitance measurement.
      Fluorescence imaging of ZIMIR-labeled beta cells followed the dynamics of
      exocytotic activity at subcellular resolution, even when using simple
      epifluorescence microscopy, and located the chief sites of insulin release to
      intercellular junctions. Moreover, ZIMIR imaging of intact rat islets revealed
      that Zn(2+)/insulin release occurred largely in small groups of adjacent beta
      cells, with each forming a "secretory unit." Concurrent imaging of ZIMIR and Fura
      2 showed that the amplitude of cytosolic Ca(2+) elevation did not necessarily
      correlate with insulin secretion activity, suggesting that events downstream of
      Ca(2+) signaling underlie the cell-cell heterogeneity in insulin release. In
      addition to studying stimulation-secretion coupling in cells with Zn(2+)
      containing granules, ZIMIR may find applications in beta-cell engineering and
      screening for molecules regulating insulin secretion on high-throughput
      platforms.

PMID- 22160694
TI  - Avoidance of overheating and selection for both hair loss and bipedality in
      hominins.
AB  - Two frequently debated aspects of hominin evolution are the development of
      upright bipedal stance and reduction in body hair. It has long been argued, on
      the basis of heat-balance models, that thermoregulation might have been important
      in the evolution of both of these traits. Previous models were based on a
      stationary individual standing in direct sunlight; here we extend this approach
      to consider a walking hominin, having argued that walking is more thermally
      challenging than remaining still. Further, stationary activities may be more
      compatible with shade seeking than activities (such as foraging) involving travel
      across the landscape. Our model predictions suggest that upright stance probably
      evolved for nonthermoregulatory reasons. However, the thermoregulatory
      explanation for hair loss was supported. Specifically, we postulate progressive
      hair loss being selected and this allowing individuals to be active in hot, open
      environments initially around dusk and dawn without overheating. Then, as our
      ancestors' hair loss increased and sweating ability improved over evolutionary
      time, the fraction of the day when they could remain active in such environments
      extended. Our model suggests that only when hair loss and sweating ability reach
      near-modern human levels could hominins have been active in the heat of the day
      in hot, open environments.

PMID- 22160695
TI  - Whole-body deletion of LPS-induced TNF-alpha factor (LITAF) markedly improves
      experimental endotoxic shock and inflammatory arthritis.
AB  - LPS-induced TNF-alpha factor (LITAF) mediates cytokine expression in response to
      endotoxin challenge. Previously, we reported that macrophage-specific LITAF
      deficient (macLITAF-/-) mice exposed to LPS have a delayed onset in the serum
      levels of proinflammatory cytokines and prolonged persistence of anti
      inflammatory cytokines, but only partial protection from endotoxic shock. We
      postulated that greater protection might be achieved if LITAF were deleted from
      all LITAF-producing cells, including macrophages. Using a Cre-loxP system, we
      engineered a tamoxifen-induced recombination mouse [tamLITAF(i)-/-] that resulted
      in whole-body LITAF deficiency. Our findings demonstrate that (i) tamLITAF(i)-/-
      mice are more resistant to systemic Escherichia coli LPS-induced lethality than
      our previous macLITAF-/- mice, providing evidence that LITAF-producing cells
      other than LysMCre-positive cells play an important role in mediating endotoxic
      shock; (ii) tamLITAF(i)-/- mice show a similar pattern of cytokine expression
      with decreased proinflammatory and prolonged anti-inflammatory mediators compared
      with WT mice; and (iii) tamLITAF(i)-/- mice, compared with WT mice, display a
      significant reduction in bone resorption and inflammation associated with a local
      chronic inflammatory disease--namely, collagen antibody-induced arthritis. Our
      findings offer a unique model to study the role of LITAF in systemic and chronic
      local inflammatory processes, and pave the way for anti-LITAF therapeutic
      approaches for the treatment of TNF-mediated inflammatory diseases.

PMID- 22160696
TI  - The mirror game as a paradigm for studying the dynamics of two people improvising
      motion together.
AB  - Joint improvisation is the creative action of two or more people without a script
      or designated leader. Examples include improvisational theater and music, and day
      to-day activities such as conversations. In joint improvisation, novel action is
      created, emerging from the interaction between people. Although central to
      creative processes and social interaction, joint improvisation remains largely
      unexplored due to the lack of experimental paradigms. Here we introduce a
      paradigm based on a theater practice called the mirror game. We measured the hand
      motions of two people mirroring each other at high temporal and spatial
      resolution. We focused on expert actors and musicians skilled in joint
      improvisation. We found that players can jointly create novel complex motion
      without a designated leader, synchronized to less than 40 ms. In contrast, we
      found that designating one player as leader deteriorated performance: The
      follower showed 2-3 Hz oscillation around the leader's smooth trajectory,
      decreasing synchrony and reducing the range of velocities reached. A mathematical
      model suggests a mechanism for these observations based on mutual agreement on
      future motion in mirrored reactive-predictive controllers. This is a step toward
      understanding the human ability to create novelty by improvising together.

PMID- 22160697
TI  - Structural and energetic evidence for highly peptide-specific tumor antigen
      targeting via allo-MHC restriction.
AB  - Immunotherapies targeting peptides presented by allogeneic MHC molecules offer
      the prospect of circumventing tolerance to key tumor-associated self-antigens.
      However, the degree of antigen specificity mediated by alloreactive T cells, and
      their ability to discriminate normal tissues from transformed cells presenting
      elevated antigen levels, is poorly understood. We examined allorecognition of an
      HLA-A2-restricted Hodgkin's lymphoma-associated antigen and were able to isolate
      functionally antigen-specific allo-HLA-A2-restricted T cells from multiple
      donors. Binding and structural studies, focused on a prototypic allo-HLA-A2
      restricted T-cell receptor (TCR) termed NB20 derived from an HLA-A3 homozygote,
      suggested highly peptide-specific allorecognition that was energetically focused
      on antigen, involving direct recognition of a distinct allopeptide presented
      within a conserved MHC recognition surface. Although NB20/HLA-A2 affinity was
      unremarkable, TCR/MHC complexes were very short-lived, consistent with suboptimal
      TCR triggering and tolerance to low antigen levels. These data provide strong
      molecular evidence that within the functionally heterogeneous alloreactive
      repertoire, there is the potential for highly antigen-specific "allo-MHC
      restricted" recognition and suggest a kinetic mechanism whereby allo-MHC
      restricted T cells may discriminate normal from transformed tissue, thereby
      outlining a suitable basis for broad-based therapeutic targeting of tolerizing
      tumor antigens.

PMID- 22160698
TI  - Mature clustered, regularly interspaced, short palindromic repeats RNA (crRNA)
      length is measured by a ruler mechanism anchored at the precursor processing
      site.
AB  - Precise RNA processing is fundamental to all small RNA-mediated interference
      pathways. In prokaryotes, clustered, regularly interspaced, short palindromic
      repeats (CRISPR) loci encode small CRISPR RNAs (crRNAs) that protect against
      invasive genetic elements by antisense targeting. CRISPR loci are transcribed as
      a long precursor that is cleaved within repeat sequences by CRISPR-associated
      (Cas) proteins. In many organisms, this primary processing generates crRNA
      intermediates that are subject to additional nucleolytic trimming to render
      mature crRNAs of specific lengths. The molecular mechanisms underlying this
      maturation event remain poorly understood. Here, we defined the genetic
      requirements for crRNA primary processing and maturation in Staphylococcus
      epidermidis. We show that changes in the position of the primary processing site
      result in extended or diminished maturation to generate mature crRNAs of constant
      length. These results indicate that crRNA maturation occurs by a ruler mechanism
      anchored at the primary processing site. We also show that maturation is mediated
      by specific cas genes distinct from those genes involved in primary processing,
      showing that this event is directed by CRISPR/Cas loci.

PMID- 22160699
TI  - High-throughput VDJ sequencing for quantification of minimal residual disease in
      chronic lymphocytic leukemia and immune reconstitution assessment.
AB  - The primary cause of poor outcome following allogeneic hematopoietic cell
      transplantation (HCT) for chronic lymphocytic leukemia (CLL) is disease
      recurrence. Detection of increasing minimal residual disease (MRD) following HCT
      may permit early intervention to prevent clinical relapse; however, MRD
      quantification remains an uncommon diagnostic test because of logistical and
      financial barriers to widespread use. Here we describe a method for quantifying
      CLL MRD using widely available consensus primers for amplification of all Ig
      heavy chain (IGH) genes in a mixture of peripheral blood mononuclear cells,
      followed by high-throughput sequencing (HTS) for disease-specific IGH sequence
      quantification. To achieve accurate MRD quantification, we developed a systematic
      bioinformatic methodology to aggregate cancer clone sequence variants arising
      from systematic and random artifacts occurring during IGH-HTS. We then compared
      the sensitivity of IGH-HTS, flow cytometry, and allele-specific oligonucleotide
      PCR for MRD quantification in 28 samples collected from 6 CLL patients following
      allogeneic HCT. Using amplimer libraries generated with consensus primers from
      patient blood samples, we demonstrate the sensitivity of IGH-HTS with 454
      pyrosequencing to be 10(-5), with a high correlation between quantification by
      allele-specific oligonucleotide PCR and IGH-HTS (r = 0.85). From the same dataset
      used to quantify MRD, IGH-HTS also allowed us to profile IGH repertoire
      reconstitution after HCT-information not provided by the other MRD methods. IGH
      HTS using consensus primers will broaden the availability of MRD quantification
      in CLL and other B cell malignancies, and this approach has potential for
      quantitative evaluation of immune diversification following transplant and
      nontransplant therapies.

PMID- 22160700
TI  - Specific neural substrate linking respiration to locomotion.
AB  - When animals move, respiration increases to adapt for increased energy demands;
      the underlying mechanisms are still not understood. We investigated the neural
      substrates underlying the respiratory changes in relation to movement in
      lampreys. We showed that respiration increases following stimulation of the
      mesencephalic locomotor region (MLR) in an in vitro isolated preparation, an
      effect that persists in the absence of the spinal cord and caudal brainstem. By
      using electrophysiological and anatomical techniques, including whole-cell patch
      recordings, we identified a subset of neurons located in the dorsal MLR that send
      direct inputs to neurons in the respiratory generator. In semi-intact
      preparations, blockade of this region with 6-cyano-7-nitroquinoxaline-2,3-dione
      and (2R)-amino-5-phosphonovaleric acid greatly reduced the respiratory increases
      without affecting the locomotor movements. These results show that neurons in the
      respiratory generator receive direct glutamatergic connections from the MLR and
      that a subpopulation of MLR neurons plays a key role in the respiratory changes
      linked to movement.

PMID- 22160701
TI  - Structural basis for basal activity and autoactivation of abscisic acid (ABA)
      signaling SnRK2 kinases.
AB  - Abscisic acid (ABA) is an essential hormone that controls plant growth,
      development, and responses to abiotic stresses. Central for ABA signaling is the
      ABA-mediated autoactivation of three monomeric Snf1-related kinases (SnRK2.2, 
      2.3, and -2.6). In the absence of ABA, SnRK2s are kept in an inactive state by
      forming physical complexes with type 2C protein phosphatases (PP2Cs). Upon relief
      of this inhibition, SnRK2 kinases can autoactivate through unknown mechanisms.
      Here, we report the crystal structures of full-length Arabidopsis thaliana
      SnRK2.3 and SnRK2.6 at 1.9- and 2.3-A resolution, respectively. The structures,
      in combination with biochemical studies, reveal a two-step mechanism of
      intramolecular kinase activation that resembles the intermolecular activation of
      cyclin-dependent kinases. First, release of inhibition by PP2C allows the SnRK2s
      to become partially active because of an intramolecular stabilization of the
      catalytic domain by a conserved helix in the kinase regulatory domain. This
      stabilization enables SnRK2s to gain full activity by activation loop
      autophosphorylation. Autophosphorylation is more efficient in SnRK2.6, which has
      higher stability than SnRK2.3 and has well-structured activation loop phosphate
      acceptor sites that are positioned next to the catalytic site. Together, these
      data provide a structural framework that links ABA-mediated release of PP2C
      inhibition to activation of SnRK2 kinases.

PMID- 22160702
TI  - Hunter-gatherers and other primates as prey, predators, and competitors of
      snakes.
AB  - Relationships between primates and snakes are of widespread interest from
      anthropological, psychological, and evolutionary perspectives, but surprisingly,
      little is known about the dangers that serpents have posed to people with
      prehistoric lifestyles and nonhuman primates. Here, we report ethnographic
      observations of 120 Philippine Agta Negritos when they were still preliterate
      hunter-gatherers, among whom 26% of adult males had survived predation attempts
      by reticulated pythons. Six fatal attacks occurred between 1934 and 1973. Agta
      ate pythons as well as deer, wild pigs, and monkeys, which are also eaten by
      pythons, and therefore, the two species were reciprocally prey, predators, and
      potential competitors. Natural history data document snake predation on tree
      shrews and 26 species of nonhuman primates as well as many species of primates
      approaching, mobbing, killing, and sometimes eating snakes. These findings,
      interpreted within the context of snake and primate phylogenies, corroborate the
      hypothesis that complex ecological interactions have long characterized our
      shared evolutionary history.

PMID- 22160703
TI  - Retinoblastoma (Rb) regulates laminar dendritic arbor reorganization in retinal
      horizontal neurons.
AB  - Neuronal differentiation with respect to the acquisition of synaptic competence
      needs to be regulated precisely during neurogenesis to ensure proper formation of
      circuits at the right place and time in development. This regulation is
      particularly important for synaptic triads among photoreceptors, horizontal cells
      (HCs), and bipolar cells in the retina, because HCs are among the first cell
      types produced during development, and bipolar cells are among the last. HCs
      undergo a dramatic transition from vertically oriented neurites that form
      columnar arbors to overlapping laminar dendritic arbors with differentiation.
      However, how this process is regulated and coordinated with differentiation of
      photoreceptors and bipolar cells remains unknown. Previous studies have suggested
      that the retinoblastoma (Rb) tumor suppressor gene may play a role in horizontal
      cell differentiation and synaptogenesis. By combining genetic mosaic analysis of
      individual synaptic triads with neuroanatomic analyses and multiphoton live
      imaging of developing HCs, we found that Rb plays a cell-autonomous role in the
      reorganization of horizontal cell neurites as they differentiate. Aberrant
      vertical processes in Rb-deficient HCs form ectopic synapses with rods in the
      outer nuclear layer but lack bipolar dendrites. Although previous reports
      indicate that photoreceptor abnormalities can trigger formation of ectopic
      synapses, our studies now demonstrate that defects in a postsynaptic partner
      contribute to the formation of ectopic photoreceptor synapses in the mammalian
      retina.

PMID- 22160704
TI  - Spontaneous generation of anchorless prions in transgenic mice.
AB  - Some prion protein mutations create anchorless molecules that cause Gerstmann
      Straussler-Scheinker (GSS) disease. To model GSS, we generated transgenic mice
      expressing cellular prion protein (PrP(C)) lacking the glycosylphosphatidyl
      inositol (GPI) anchor, denoted PrP(DeltaGPI). Mice overexpressing PrP(DeltaGPI)
      developed a late-onset, spontaneous neurologic dysfunction characterized by
      widespread amyloid deposition in the brain and the presence of a short protease
      resistant PrP fragment similar to those found in GSS patients. In
      Tg(PrP,DeltaGPI) mice, disease onset could be accelerated either by inoculation
      with brain homogenate prepared from spontaneously ill animals or by coexpression
      of membrane-anchored, full-length PrP(C). In contrast, coexpression of N
      terminally truncated PrP(Delta23-88) did not affect disease progression.
      Remarkably, disease from ill Tg(PrP,DeltaGPI) mice transmitted to mice expressing
      wild-type PrP(C), indicating the spontaneous generation of prions.

PMID- 22160705
TI  - Variable motif utilization in homeotic selector (Hox)-cofactor complex formation
      controls specificity.
AB  - Homeotic selector (Hox) proteins often bind DNA cooperatively with cofactors such
      as Extradenticle (Exd) and Homothorax (Hth) to achieve functional specificity in
      vivo. Previous studies identified the Hox YPWM motif as an important Exd
      interaction motif. Using a comparative approach, we characterize the contribution
      of this and additional conserved sequence motifs to the regulation of specific
      target genes for three Drosophila Hox proteins. We find that Sex combs reduced
      (Scr) uses a simple interaction mechanism, where a single tryptophan-containing
      motif is necessary for Exd-dependent DNA-binding and in vivo functions. Abdominal
      A (AbdA) is more complex, using multiple conserved motifs in a context-dependent
      manner. Lastly, Ultrabithorax (Ubx) is the most flexible, in that it uses
      multiple conserved motifs that function in parallel to regulate target genes in
      vivo. We propose that using different binding mechanisms with the same cofactor
      may be one strategy to achieve functional specificity in vivo.

PMID- 22160706
TI  - microRNA-34a regulates neurite outgrowth, spinal morphology, and function.
AB  - The p53 family member TAp73 is a transcription factor that plays a key role in
      many biological processes, including neuronal development. In particular, we have
      shown that p73 drives the expression of miR-34a, but not miR-34b and c, in mouse
      cortical neurons. miR-34a in turn modulates the expression of synaptic targets
      including synaptotagmin-1 and syntaxin-1A. Here we show that this axis is
      retained in mouse ES cells committed to differentiate toward a neurological
      phenotype. Moreover, overexpression of miR-34a alters hippocampal spinal
      morphology, and results in electrophysiological changes consistent with a
      reduction in spinal function. Therefore, the TAp73/miR-34a axis has functional
      relevance in primary neurons. These data reinforce a role for miR-34a in neuronal
      development.

PMID- 22160707
TI  - Drosophila Piwi functions downstream of piRNA production mediating a chromatin
      based transposon silencing mechanism in female germ line.
AB  - Transposon control is a critical process during reproduction. The PIWI family
      proteins can play a key role, using a piRNA-mediated slicing mechanism to
      suppress transposon activity posttranscriptionally. In Drosophila melanogaster,
      Piwi is predominantly localized in the nucleus and has been implicated in
      heterochromatin formation. Here, we use female germ-line-specific depletion to
      study Piwi function. This depletion of Piwi leads to infertility and to axis
      specification defects in the developing egg chambers; correspondingly, widespread
      loss of transposon silencing is observed. Germ-line Piwi does not appear to be
      required for piRNA production. Instead, Piwi requires Aubergine (and presumably
      secondary piRNA) for proper localization. A subset of transposons that show
      significant overexpression in germ-line Piwi-depleted ovaries exhibit a
      corresponding loss of HP1a and H3K9me2. Germ-line HP1a depletion also leads to a
      loss of transposon silencing, demonstrating the functional requirement for HP1a
      enrichment at these loci. Considering our results and those of others, we infer
      that germ-line Piwi functions downstream of piRNA production to promote silencing
      of some transposons via recruitment of HP1a. Thus, in addition to its better
      known function in posttranscriptional silencing, piRNA also appears to function
      in a targeting mechanism for heterochromatin formation mediated by Piwi.

PMID- 22160708
TI  - Transcranial magnetic stimulation modulates the brain's intrinsic activity in a
      frequency-dependent manner.
AB  - Intrinsic activity in the brain is organized into networks. Although constrained
      by their anatomical connections, functional correlations between nodes of these
      networks reorganize dynamically. Dynamic organization implies that couplings
      between network nodes can be reconfigured to support processing demands. To
      explore such reconfigurations, we combined repetitive transcranial magnetic
      stimulation (rTMS) and functional connectivity MRI (fcMRI) to modulate cortical
      activity in one node of the default network, and assessed the effect of this upon
      functional correlations throughout the network. Two different frequencies of rTMS
      to the same default network node (the left posterior inferior parietal lobule,
      lpIPL) induced two topographically distinct changes in functional connectivity.
      High-frequency rTMS to lpIPL decreased functional correlations between cortical
      default network nodes, but not between these nodes and the hippocampal formation.
      In contrast, low frequency rTMS to lpIPL did not alter connectivity between
      cortical default network nodes, but increased functional correlations between
      lpIPL and the hippocampal formation. These results suggest that the default
      network is composed of (at least) two subsystems. More broadly, the finding that
      two rTMS stimulation regimens to the same default network node have distinct
      effects reveals that this node is embedded within a network that possesses
      multiple, functionally distinct relationships among its distributed partners.

PMID- 22160710
TI  - Retraction for Dougan et al., Probing osmolyte participation in the unfolding
      transition state of a protein.

PMID- 22160709
TI  - Parallel up-regulation of the profilin gene family following independent
      domestication of diploid and allopolyploid cotton (Gossypium).
AB  - Cotton is remarkable among our major crops in that four species were
      independently domesticated, two allopolyploids and two diploids. In each case
      thousands of years of human selection transformed sparsely flowering, perennial
      shrubs into highly productive crops with seeds bearing the vastly elongated and
      abundant single-celled hairs that comprise modern cotton fiber. The genetic
      underpinnings of these transformations are largely unknown, but comparative gene
      expression profiling experiments have demonstrated up-regulation of profilin
      accompanying domestication in all three species for which wild forms are known.
      Profilins are actin monomer binding proteins that are important in cytoskeletal
      dynamics and in cotton fiber elongation. We show that Gossypium diploids contain
      six profilin genes (GPRF1-GPRF6), located on four different chromosomes (eight
      chromosomes in the allopolyploid). All but one profilin (GPRF6) are expressed
      during cotton fiber development, and both homeologs of GPRF1-GPRF5 are expressed
      in fibers of the allopolyploids. Remarkably, quantitative RT-PCR and RNAseq data
      demonstrate that GPRF1-GPRF5 are all up-regulated, in parallel, in the three
      independently domesticated cottons in comparison with their wild counterparts.
      This result was additionally supported by iTRAQ proteomic data. In the
      allopolyploids, there This usage of novel should be fine, since it refers to a
      novel evolutionary process, not a novel discovery has been novel recruitment of
      the sixth profilin gene (GPRF6) as a result of domestication. This parallel up
      regulation of an entire gene family in multiple species in response to strong
      directional selection is without precedent and suggests unwitting selection on
      one or more upstream transcription factors or other proteins that coordinately
      exercise control over profilin expression.

PMID- 22160712
TI  - Retraction for Dougan et al., Solvent molecules bridge the mechanical unfolding
      transition state of a protein.

PMID- 22160711
TI  - Carbon and sulfur back flux during anaerobic microbial oxidation of methane and
      coupled sulfate reduction.
AB  - Microbial degradation of substrates to terminal products is commonly understood
      as a unidirectional process. In individual enzymatic reactions, however,
      reversibility (reverse reaction and product back flux) is common. Hence, it is
      possible that entire pathways of microbial degradation are associated with back
      flux from the accumulating product pool through intracellular intermediates into
      the substrate pool. We investigated carbon and sulfur back flux during the
      anaerobic oxidation of methane (AOM) with sulfate, one of the least exergonic
      microbial catabolic processes known. The involved enzymes must operate not far
      from the thermodynamic equilibrium. Such an energetic situation is likely to
      favor product back flux. Indeed, cultures of highly enriched archaeal-bacterial
      consortia, performing net AOM with unlabeled methane and sulfate, converted label
      from (14)C-bicarbonate and (35)S-sulfide to (14)C-methane and (35)S-sulfate,
      respectively. Back fluxes reached 5% and 13%, respectively, of the net AOM rate.
      The existence of catabolic back fluxes in the reverse direction of net reactions
      has implications for biogeochemical isotope studies. In environments where
      biochemical processes are close to thermodynamic equilibrium, measured fluxes of
      labeled substrates to products are not equal to microbial net rates. Detection of
      a reaction in situ by labeling may not even indicate a net reaction occurring in
      the direction of label conversion but may reflect the reverse component of a so
      far unrecognized net reaction. Furthermore, the natural isotopic composition of
      the substrate and product pool will be determined by both the forward and back
      flux. This finding may have to be considered in the interpretation of stable
      isotope records.

PMID- 22160713
TI  - Rapid experience-dependent plasticity of synapse function and structure in ferret
      visual cortex in vivo.
AB  - The rules by which visual experience influences neuronal responses and structure
      in the developing brain are not well understood. To elucidate the relationship
      between rapid functional changes and dendritic spine remodeling in vivo, we
      carried out chronic imaging experiments that tracked visual responses and
      dendritic spines in the ferret visual cortex following brief periods of monocular
      deprivation. Functional changes, which were largely driven by loss of deprived
      eye responses, were tightly regulated with structural changes at the level of
      dendritic spines, and occurred very rapidly (on a timescale of hours). The
      magnitude of functional changes was correlated with the magnitude of structural
      changes across the cortex, and both these features reversed when the deprived eye
      was reopened. A global rule governed how the responses to the two eyes or changes
      in spines were altered by monocular deprivation: the changes occurred
      irrespective of regional ocular dominance preference and were independently
      mediated by each eye, and the loss or gain of responses/spines occurred as a
      constant proportion of predeprivation drive by the deprived or nondeprived eye,
      respectively.

PMID- 22160715
TI  - Histone deacetylase inhibitors prevent the degradation and restore the activity
      of glucocerebrosidase in Gaucher disease.
AB  - Gaucher disease (GD) is caused by a spectrum of genetic mutations within the gene
      encoding the lysosomal enzyme glucocerebrosidase (GCase). These mutations often
      lead to misfolded proteins that are recognized by the unfolded protein response
      system and are degraded through the ubiquitin-proteasome pathway. Modulating this
      pathway with histone deacetylase inhibitors (HDACis) has been shown to improve
      protein stability in other disease settings. To identify the mechanisms involved
      in the regulation of GCase and determine the effects of HDACis on protein
      stability, we investigated the most prevalent mutations for nonneuronopathic
      (N370S) and neuronopathic (L444P) GD in cultured fibroblasts derived from GD
      patients and HeLa cells transfected with these mutations. The half-lives of
      mutant GCase proteins correspond to decreases in protein levels and enzymatic
      activity. GCase was found to bind to Hsp70, which directed the protein to TCP1
      for proper folding, and to Hsp90, which directed the protein to the ubiquitin
      proteasome pathway. Using a known HDACi (SAHA) and a unique small-molecule HDACi
      (LB-205), GCase levels increased rescuing enzymatic activity in mutant cells. The
      increase in the quantity of protein can be attributed to increases in protein
      half-life that correspond primarily with a decrease in degradation rather than an
      increase in chaperoned folding. HDACis reduce binding to Hsp90 and prevent
      subsequent ubiquitination and proteasomal degradation without affecting binding
      to Hsp70 or TCP1. These findings provide insight into the pathogenesis of GD and
      indicate a potent therapeutic potential of HDAC inhibitors for the treatment of
      GD and other human protein misfolding disorders.

PMID- 22160714
TI  - Structural basis for gating charge movement in the voltage sensor of a sodium
      channel.
AB  - Voltage-dependent gating of ion channels is essential for electrical signaling in
      excitable cells, but the structural basis for voltage sensor function is unknown.
      We constructed high-resolution structural models of resting, intermediate, and
      activated states of the voltage-sensing domain of the bacterial sodium channel
      NaChBac using the Rosetta modeling method, crystal structures of related
      channels, and experimental data showing state-dependent interactions between the
      gating charge-carrying arginines in the S4 segment and negatively charged
      residues in neighboring transmembrane segments. The resulting structural models
      illustrate a network of ionic and hydrogen-bonding interactions that are made
      sequentially by the gating charges as they move out under the influence of the
      electric field. The S4 segment slides 6-8 A outward through a narrow groove
      formed by the S1, S2, and S3 segments, rotates ~30 degrees , and tilts sideways
      at a pivot point formed by a highly conserved hydrophobic region near the middle
      of the voltage sensor. The S4 segment has a 3(10)-helical conformation in the
      narrow inner gating pore, which allows linear movement of the gating charges
      across the inner one-half of the membrane. Conformational changes of the
      intracellular one-half of S4 during activation are rigidly coupled to lateral
      movement of the S4-S5 linker, which could induce movement of the S5 and S6
      segments and open the intracellular gate of the pore. We confirmed the validity
      of these structural models by comparing with a high-resolution structure of a
      NaChBac homolog and showing predicted molecular interactions of hydrophobic
      residues in the S4 segment in disulfide-locking studies.

PMID- 22160717
TI  - QnAs with John A. Rogers. Interview by Prashant Nair.

PMID- 22160716
TI  - Membrane protein complexes catalyze both 4- and 3-hydroxylation of cinnamic acid
      derivatives in monolignol biosynthesis.
AB  - The hydroxylation of 4- and 3-ring carbons of cinnamic acid derivatives during
      monolignol biosynthesis are key steps that determine the structure and properties
      of lignin. Individual enzymes have been thought to catalyze these reactions. In
      stem differentiating xylem (SDX) of Populus trichocarpa, two cinnamic acid 4
      hydroxylases (PtrC4H1 and PtrC4H2) and a p-coumaroyl ester 3-hydroxylase
      (PtrC3H3) are the enzymes involved in these reactions. Here we present evidence
      that these hydroxylases interact, forming heterodimeric (PtrC4H1/C4H2,
      PtrC4H1/C3H3, and PtrC4H2/C3H3) and heterotrimeric (PtrC4H1/C4H2/C3H3) membrane
      protein complexes. Enzyme kinetics using yeast recombinant proteins demonstrated
      that the enzymatic efficiency (V(max)/k(m)) for any of the complexes is 70-6,500
      times greater than that of the individual proteins. The highest increase in
      efficiency was found for the PtrC4H1/C4H2/C3H3-mediated p-coumaroyl ester 3
      hydroxylation. Affinity purification-quantitative mass spectrometry, bimolecular
      fluorescence complementation, chemical cross-linking, and reciprocal
      coimmunoprecipitation provide further evidence for these multiprotein complexes.
      The activities of the recombinant and SDX plant proteins demonstrate two protein
      complex-mediated 3-hydroxylation paths in monolignol biosynthesis in P.
      trichocarpa SDX; one converts p-coumaric acid to caffeic acid and the other
      converts p-coumaroyl shikimic acid to caffeoyl shikimic acid. Cinnamic acid 4
      hydroxylation is also mediated by the same protein complexes. These results
      provide direct evidence for functional involvement of membrane protein complexes
      in monolignol biosynthesis.

PMID- 22160718
TI  - Geoengineering: the good, the MAD, and the sensible.

PMID- 22160719
TI  - Reverse signaling through the costimulatory ligand CD137L in epithelial cells is
      essential for natural killer cell-mediated acute tissue inflammation.
AB  - Renal ischemia-reperfusion injury (IRI) after kidney transplantation is a major
      cause of delayed graft function. Even though IRI is recognized as a highly
      coordinated and specific process, the pathways and mechanisms through which the
      innate response is activated are poorly understood. In this study, we used a
      mouse model of acute kidney IRI to examine whether the interactions of
      costimulatory receptor CD137 and its ligand (CD137L) are involved in the early
      phase of acute kidney inflammation caused by IRI. We report here that the
      specific expressions of CD137 on natural killer cells and of CD137L on tubular
      epithelial cells (TECs) are required for acute kidney IRI. Reverse signaling
      through CD137L in TECs results in their production of the chemokine (C-X-C motif)
      receptor 2 ligands CXCL1 and CXCL2 and the subsequent induction of neutrophil
      recruitment, resulting in a cascade of proinflammatory events during kidney IRI.
      Our findings identify an innate pathogenic pathway for renal IRI involving the
      natural killer cell-TEC-neutrophil axis, whereby CD137-CD137L interactions
      provide the causal contribution of epithelial cell dysregulation to renal IRI.
      The CD137L reverse signaling pathway in epithelial cells therefore may represent
      a good target for blocking the initial stage of inflammatory diseases, including
      renal IRI.

PMID- 22160720
TI  - Dysregulation of Kruppel-like factor 4 during brain development leads to
      hydrocephalus in mice.
AB  - Kruppel-like factor 4 (KLF4) is involved in self-renewal of embryonic stem cells
      and reprogramming of somatic cells to pluripotency. However, its role in lineage
      committed stem cells remains largely unknown. Here, we show that KLF4 is
      expressed in neural stem cells (NSCs) and is down-regulated during neuronal
      differentiation. Unexpectedly, enhanced expression of KLF4 reduces self-renewal
      of cultured NSCs and inhibits proliferation of subventricular neural precursors
      in transgenic mice. Mice with increased KLF4 in NSCs and NSCs-derived ependymal
      cells developed hydrocephalus-like characteristics, including enlarged
      ventricles, thinned cortex, agenesis of the corpus callosum, and significantly
      reduced subcommissural organ. These characteristics were accompanied by elevation
      of GFAP expression and astrocyte hypertrophy. The ventricular cilia, vital for
      cerebrospinal fluid flow, are also disrupted in the mutant mice. These results
      indicate that down-regulation of KLF4 is critical for neural development and its
      dysregulation may lead to hydrocephalus.

PMID- 22160721
TI  - Experience-dependent regulation of CaMKII activity within single visual cortex
      synapses in vivo.
AB  - Unbalanced visual input during development induces persistent alterations in the
      function and structure of visual cortical neurons. The molecular mechanisms that
      drive activity-dependent changes await direct visualization of underlying signals
      at individual synapses in vivo. By using a genetically engineered Forster
      resonance energy transfer (FRET) probe for the detection of CaMKII activity, and
      two-photon imaging of single synapses within identified functional domains, we
      have revealed unexpected and differential mechanisms in specific subsets of
      synapses in vivo. Brief monocular deprivation leads to activation of CaMKII in
      most synapses of layer 2/3 pyramidal cells within deprived eye domains, despite
      reduced visual drive, but not in nondeprived eye domains. Synapses that are
      eliminated in deprived eye domains have low basal CaMKII activity, implying a
      protective role for activated CaMKII against synapse elimination.

PMID- 22160722
TI  - Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of
      oligodendrocyte myelination.
AB  - A requisite component of nervous system development is the achievement of
      cellular recognition and spatial segregation through competition-based refinement
      mechanisms. Competition for available axon space by myelinating oligodendrocytes
      ensures that all relevant CNS axons are myelinated properly. To ascertain the
      nature of this competition, we generated a transgenic mouse with sparsely labeled
      oligodendrocytes and establish that individual oligodendrocytes occupying similar
      axon tracts can greatly vary the number and lengths of their myelin internodes.
      Here we show that intercellular interactions between competing oligodendroglia
      influence the number and length of myelin internodes, referred to as myelinogenic
      potential, and identify the amino-terminal region of Nogo-A, expressed by
      oligodendroglia, as necessary and sufficient to inhibit this process. Exuberant
      and expansive myelination/remyelination is detected in the absence of Nogo during
      development and after demyelination, suggesting that spatial segregation and
      myelin extent is limited by microenvironmental inhibition. We demonstrate a
      unique physiological role for Nogo-A in the precise myelination of the developing
      CNS. Maximizing the myelinogenic potential of oligodendrocytes may offer an
      effective strategy for repair in future therapies for demyelination.

PMID- 22160723
TI  - Human monocytes are severely impaired in base and DNA double-strand break repair
      that renders them vulnerable to oxidative stress.
AB  - Monocytes are key players in the immune system. Crossing the blood barrier, they
      infiltrate tissues and differentiate into (i) macrophages that fight off
      pathogens and (ii) dendritic cells (DCs) that activate the immune response. A
      hallmark of monocyte/macrophage activation is the generation of reactive oxygen
      species (ROS) as a defense against invading microorganisms. How monocytes,
      macrophages, and DCs in particular respond to ROS is largely unknown. Here we
      studied the sensitivity of primary human monocytes isolated from peripheral blood
      and compared them with macrophages and DCs derived from them by cytokine
      maturation following DNA damage induced by ROS. We show that monocytes are
      hypersensitive to ROS, undergoing excessive apoptosis. These cells exhibited a
      high yield of ROS-induced DNA single- and double-strand breaks and activation of
      the ATR-Chk1-ATM-Chk2-p53 pathway that led to Fas and caspase-8, -3, and -7
      activation, whereas macrophages and DCs derived from them were protected.
      Monocytes are also hypersensitive to ionizing radiation and oxidized low-density
      lipoprotein. The remarkable sensitivity of monocytes to oxidative stress is
      caused by a lack of expression of the DNA repair proteins XRCC1, ligase IIIalpha,
      poly(ADP-ribose) polymerase-1, and catalytic subunit of DNA-dependent protein
      kinase (DNA-PK(cs)), causing a severe DNA repair defect that impacts base
      excision repair and double-strand break repair by nonhomologous end-joining.
      During maturation of monocytes into macrophages and DCs triggered by the
      cytokines GM-CSF and IL-4, these proteins become up-regulated, making macrophages
      and DCs repair-competent and ROS-resistant. We propose that impaired DNA repair
      in monocytes plays a role in the regulation of the monocyte/macrophage/DC system
      following ROS exposure.

PMID- 22160724
TI  - Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic
      viral infection.
AB  - CD4 T cells play a critical role in regulating CD8 T-cell responses during
      chronic viral infection. Several studies in animal models and humans have shown
      that the absence of CD4 T-cell help results in severe dysfunction of virus
      specific CD8 T cells. However, whether function can be restored in already
      exhausted CD8 T cells by providing CD4 T-cell help at a later time remains
      unexplored. In this study, we used a mouse model of chronic lymphocytic
      choriomeningitis virus (LCMV) infection to address this question. Adoptive
      transfer of LCMV-specific CD4 T cells into chronically infected mice restored
      proliferation and cytokine production by exhausted virus-specific CD8 T cells and
      reduced viral burden. Although the transferred CD4 T cells were able to enhance
      function in exhausted CD8 T cells, these CD4 T cells expressed high levels of the
      programmed cell death (PD)-1 inhibitory receptor. Blockade of the PD-1 pathway
      increased the ability of transferred LCMV-specific CD4 T cells to produce
      effector cytokines, improved rescue of exhausted CD8 T cells, and resulted in a
      striking reduction in viral load. These results suggest that CD4 T-cell
      immunotherapy alone or in conjunction with blockade of inhibitory receptors may
      be a promising approach for treating CD8 T-cell dysfunction in chronic infections
      and cancer.

PMID- 22160725
TI  - Low-affinity cation transporter (OsLCT1) regulates cadmium transport into rice
      grains.
AB  - Accumulation of cadmium (Cd) in rice (Oryza sativa L.) grains poses a potential
      health problem, especially in Asia. Most Cd in rice grains accumulates through
      phloem transport, but the molecular mechanism of this transport has not been
      revealed. In this study, we identified a rice Cd transporter, OsLCT1, involved in
      Cd transport to the grains. OsLCT1-GFP was localized at the plasma membrane in
      plant cells, and OsLCT1 showed Cd efflux activity in yeast. In rice plants,
      strong OsLCT1 expression was observed in leaf blades and nodes during the
      reproductive stage. In the uppermost node, OsLCT1 transcripts were detected
      around large vascular bundles and in diffuse vascular bundles. RNAi-mediated
      knockdown of OsLCT1 did not affect xylem-mediated Cd transport but reduced phloem
      mediated Cd transport. The knockdown plants of OsLCT1 accumulated approximately
      half as much Cd in the grains as did the control plants. The content of other
      metals in rice grains and plant growth were not negatively affected by OsLCT1
      suppression. These results suggest that OsLCT1 functions at the nodes in Cd
      transport into grains and that in a standard japonica cultivar, the regulation of
      OsLCT1 enables the generation of "low-Cd rice" without negative effects on
      agronomical traits. These findings identify a transporter gene for phloem Cd
      transport in plants.

PMID- 22160726
TI  - Resilience and stability in bird guilds across tropical countryside.
AB  - The consequences of biodiversity decline in intensified agricultural landscapes
      hinge on surviving biotic assemblages. Maintaining crucial ecosystem processes
      and services requires resilience to natural and anthropogenic disturbances.
      However, the resilience and stability of surviving biological communities remain
      poorly quantified. From a 10-y dataset comprising 2,880 bird censuses across a
      land-use gradient, we present three key findings concerning the resilience and
      stability of Costa Rican bird communities. First, seed dispersing, insect eating,
      and pollinating guilds were more resilient to low-intensity land use than high
      intensity land use. Compared with forest assemblages, bird abundance, species
      richness, and diversity were all ~15% lower in low-intensity land use and ~50%
      lower in high-intensity land use. Second, patterns in species richness generally
      correlated with patterns in stability: guilds exhibited less variation in
      abundance in low-intensity land use than in high-intensity land use. Finally,
      interspecific differences in reaction to environmental change (response
      diversity) and possibly the portfolio effect, but not negative covariance of
      species abundances, conferred resilience and stability. These findings point to
      the changes needed in agricultural production practices in the tropics to better
      sustain bird communities and, possibly, the functional and service roles that
      they play.

PMID- 22160727
TI  - Control of glucose homeostasis and insulin sensitivity by the Let-7 family of
      microRNAs.
AB  - Diabetes mellitus is the most common metabolic disorder worldwide and a major
      risk factor for cardiovascular disease. MicroRNAs are negative regulators of gene
      expression that have been implicated in many biological processes, including
      metabolism. Here we show that the Let-7 family of microRNAs regulates glucose
      metabolism in multiple organs. Global and pancreas-specific overexpression of Let
      7 in mice resulted in impaired glucose tolerance and reduced glucose-induced
      pancreatic insulin secretion. Mice overexpressing Let-7 also had decreased fat
      mass and body weight, as well as reduced body size. Global knockdown of the Let-7
      family with an antimiR was sufficient to prevent and treat impaired glucose
      tolerance in mice with diet-induced obesity, at least in part by improving
      insulin sensitivity in liver and muscle. AntimiR treatment of mice on a high-fat
      diet also resulted in increased lean and muscle mass, but not increased fat mass,
      and prevented ectopic fat deposition in the liver. These findings demonstrate
      that Let-7 regulates multiple aspects of glucose metabolism and suggest antimiR
      induced Let-7 knockdown as a potential treatment for type 2 diabetes mellitus.
      Furthermore, our Cre-inducible Let-7-transgenic mice provide a unique model for
      studying tissue-specific aspects of body growth and type 2 diabetes.

PMID- 22160728
TI  - Practical issues regarding the incorporation of PET into a busy SPECT practice.
AB  - Incorporating positron emission tomography (PET) imaging or PET/computed
      tomographic (PET/CT) imaging into a clinical cardiology practice provides
      opportunities to better assess patients as well as to expand the services offered
      by the practice. Clinical evidence continues to accrue, demonstrating the
      superior quality, the breadth of assessments possible, the diagnostic certainty
      and accuracy, and the lower patient radiation exposure of PET versus single
      photon emission computerized tomography (SPECT) myocardial perfusion imaging
      (MPI). PET imaging is more accessible to non-hospital imaging centers than ever
      before because of the availability of radiopharmaceuticals that can be generated
      on-site or delivered in unit doses from regional cyclotrons, and camera systems
      of lower cost than previously available. In this manuscript, we offer guidance on
      the many factors a practice must address before replacing an aging SPECT camera
      or adding new PET or PET/CT imaging capabilities. Key among these are defining
      the PET and CT procedures the practice members wish to perform, learning the
      equipment and radiotracers required to perform those procedures, determining
      whether their facility has sufficient physical space and shielding to accommodate
      the dedicated PET or PET/CT instrumentation, and addressing issues related to the
      practice's referral base, competition, cost-of-entry, reimbursement, and return
      on investment.

PMID- 22160729
TI  - Organ-sparing surgery of the bilateral testicular large cell calcifying sertoli
      cell tumor in patient with atypical Peutz-Jeghers syndrome.
AB  - Large cell calcifying sertoli cell tumor (LCCSCT) is an exceptionally rare
      neoplasm originating from sperm cord cells. The tumors have relatively low
      malignant potential and unlikely proceed to metastasis formation. The lesions may
      occur in an isolated form or in ca. 40% of cases may be associated with genetic
      abnormalities, by and large Peutz-Jeghers syndrome and Carney complex. At
      presentation, 20% of LCCSCT cases are bilateral and/or multifocal. Owning to
      characteristic skin lesions and particular hyperechoic ultrasound image of the
      tumor, preliminary diagnosis of the syndromic LCCSCT is possible in the
      preoperative period. Consequently, testicle organ-sparing procedure can be
      attempted, which is especially justified in bilateral lesions. Here, we report a
      case of a bilateral LCCSCT in a 20-year-old man with atypical Peutz-Jeghers
      syndrome due to amplification of the exon 1 of STK11 gene who was successfully
      treated with bilateral testicle-sparing tumorectomies.

PMID- 22160730
TI  - "My sister's hand is in my bed": a case of somatoparaphrenia.

PMID- 22160731
TI  - Transcranial sonography on Parkinson's disease and essential tremor in a Chinese
      population.
AB  - We analyzed the results of transcranial sonography (TCS) on 110 Parkinson's
      disease (PD) patients, 30 essential tremor (ET) patients and 110 controls in a
      Chinese population and compared our findings to the previous literatures. The
      echo signal intensity of midbrain substantia nigra (SN) was measured and divided
      into grade I-V. If the high echo signal intensity (grade III, IV or V) was
      detected in either side of SN, it was measured as well as the whole area of
      midbrain and the ratio of both sides of SN hyperechogenicity to the whole area of
      midbrain (S/M) were calculated. In addition, the width of the third ventricle in
      the level of thalamus was also determined. There were more individuals with the
      grade of SN >= III in PD group (100/110, 85.45%) than these in ET group (4/30,
      13.33%, x ( 2 ) = 58.38, P < 0.001) and control group (11/110, 10%, x ( 2 ) =
      125.51, P < 0.001). The median and quartile range of SN hyperechogenicity area
      and S/M in PD patients were greater than those in ET patients and controls. Both
      the area of SN hyperechogenicity >=0.2 cm(2) and the S/M >= 0.07 were useful
      indexes to distinguish PD and ET in Chinese population. In conclusion, TCS is an
      effective and useful tool to detect PD and to distinguish PD from ET in Chinese
      patients.

PMID- 22160732
TI  - The Effectiveness of Cultural Adjustment and Trauma Services (CATS): generating
      practice-based evidence on a comprehensive, school-based mental health
      intervention for immigrant youth.
AB  - A collaborative study of Cultural Adjustment and Trauma Services (CATS), a
      comprehensive, school-based mental health program for traumatized immigrant
      children and adolescents, was conducted to generate practice-based evidence on
      the service delivery model across two school districts. Program effectiveness was
      assessed by testing whether client functioning and PTSD symptoms improved as a
      result of 7 separate service elements. An array of clinical services including
      CBT, supportive therapy, and coordinating services were provided to all students,
      and an evidence-based intervention for trauma, TF-CBT, was implemented with a
      subset of students. Greater quantities of CBT and supportive therapy increased
      functioning, while greater quantities of coordinating services decreased symptoms
      of PTSD. TF-CBT services were associated with both improved functioning and PTSD
      symptoms, although TF-CBT was implemented with fidelity to the overall
      comprehensive service model rather than the structured intervention model.
      Results suggest the comprehensive school-based model was effective, though
      different service components affected different student outcomes. Implications of
      these findings for immigrant mental health interventions and implementing
      structured evidence-based practices into community mental health programs are
      discussed. Suggestions are made for future research on existing mental health
      practices with immigrants.

PMID- 22160733
TI  - Convulsions associated with the use of a synthetic cannabinoid product.
AB  - INTRODUCTION: Clinical presentations following the use of various "spice" or
      synthetic cannabinoids have included agitation, anxiety, emesis, hallucinations,
      psychosis, tachycardia, and unresponsiveness. Convulsions were described in a one
      report although there was not laboratory confirmation for synthetic cannabinoids.
      In another published report laboratory confirmation for a synthetic cannabinoid
      was done in which the patient manifested activity that was interpreted as a
      possible convulsion. CASE REPORT: We describe a patient who had two witnessed
      generalized convulsions soon after smoking a "spice" product that we later
      confirmed to have four different synthetic cannabinoids. DISCUSSION: Convulsions
      have only rarely been associated with marijuana exposures. Recreational use of
      synthetic cannabinoids is a very recent phenomenon and there is a very limited,
      albeit burgeoning, literature detailing the associated complications including
      convulsions we have reported here. The absence of anticonvulsant
      phytocannabinoids in spice products could potentially be one of multiple unknown
      mechanisms contributing to convulsions.

PMID- 22160734
TI  - A comparative theoretical study for the methanol dehydrogenation to CO over Pt3
      and PtAu2 clusters.
AB  - The density functional theory (DFT) calculations are carried out to study the
      mechanism details and the ensemble effect of methanol dehydrogenation over Pt(3)
      and PtAu(2) clusters, which present the smallest models of pure Pt clusters and
      bimetallic PtAu clusters. The energy diagrams are drawn out along both the
      initial O-H and C-H bond scission pathways via the four sequential
      dehydrogenation processes, respectively, i.e., CH(3)OH -> CH(2)OH -> CH(2)O ->
      CHO -> CO and CH(3)OH -> CH(3)O -> CH(2)O -> CHO -> CO, respectively. It is
      revealed that the reaction kinetics over PtAu(2) is significantly different from
      that over Pt(3). For the Pt(3)-mediated reaction, the C-H bond scission pathway,
      where an ensemble composed of two Pt atoms is required to complete methanol
      dehydrogenation, is energetically more favorable than the O-H bond scission
      pathway, and the maximum barrier along this pathway is calculated to be 12.99
      kcal mol(-1). In contrast, PtAu(2) cluster facilitates the reaction starting from
      the O-H bond scission, where the Pt atom acts as the active center throughout
      each elementary step of methanol dehydrogenation, and the initial O-H bond
      scission with a barrier of 21.42 kcal mol(-1) is the bottom-neck step of methanol
      decomposition. Importantly, it is shown that the complete dehydrogenation product
      of methanol, CO, can more easily dissociate from PtAu(2) cluster than from Pt(3)
      cluster. The calculated results over the model clusters provide assistance to
      some extent for understanding the improved catalytic activity of bimetal PtAu
      catalysts toward methanol oxidation in comparison with pure Pt catalysts.

PMID- 22160735
TI  - Role of forensic pathologists in mass disasters.
AB  - The forensic pathologist has always had a central role in the identification of
      the dead in every day practice, in accidents, and in disasters involving hundreds
      or thousands of victims. This role has changed in recent years, as advances in
      forensic odontology, genetics and anthropology have improved the chances of
      identifying victims beyond recognition. According to the Interpol DVI Guide,
      fingerprints, dental examination and DNA are the primary identifiers, and this
      has given new emphasis to the role of the forensic pathologist as the leader of a
      multidisciplinary team of experts in a disaster situation, based on his or her
      qualifications and the experience gained from doing the same work in the everyday
      situation of an institute of forensic medicine.

PMID- 22160736
TI  - Fatal exsanguination from hemodialysis vascular access sites.
AB  - Exsanguination from hemodialysis vascular sites may cause a rapid death. Due to
      extensive blood loss at the scene, investigators may initially suspect a homicide
      or suicide. We reviewed 100 deaths due to hemorrhage from hemodialysis shunt
      sites. The majority (81%) of these hemorrhages occurred at home and 44%
      subsequently died at home. Recognition of this medical complication at the scene
      is important to prevent the dispatch of the crime scene or homicide unit. In
      these instances, the common causes of kidney failure included hypertensive
      cardiovascular disease and diabetes mellitus. The manners of death were certified
      as therapeutic complication (93%), accident (5%), and suicide (2%). These fatal
      shunt hemorrhages are rapid and large due to their superficial subcutaneous
      locations and elevated shunt pressures from the arterial-venous anastamosis. The
      cause of death statement must include the proximate cause of death, which is
      usually the disease that resulted in kidney failure, if it is known.

PMID- 22160737
TI  - Effective use of strontium-89 in osseous metastases.
AB  - Bone is one of the organs to which cancer metastasizes most frequently. However,
      it is not a vital organ, therefore, survival after the occurrence of osseous
      metastasis is relatively favorable. Improvements of medical treatment bring
      prolonged survival to patients with osseous metastases. But this makes us to
      recognize the importance of quality of life (QOL) due to several factors,
      including pain. It is important for oncologists to know how to deal with such
      painful osseous metastases, as pain relief may enable patients to live their
      remaining lives to the fullest. Strontium-89 (89Sr) has been used worldwide as in
      Japan, while being reported to have positive effects on pain relief and QOL
      improvement in patients with osseous metastases. This review paper is aimed to
      present not only the history, roles, and medical characters of 89Sr, but also new
      aspects, such as how to use bone turnover markers, which location of osseous
      metastases is suitable for effective use of 89Sr.

PMID- 22160738
TI  - Monte Carlo simulation of scintillation photons for the design of a high
      resolution SPECT detector dedicated to human brain.
AB  - OBJECTIVE: In a typical single photon emission computed tomography (SPECT)
      system, intrinsic spatial resolution depends on the accuracy of the
      identification of an interacting point, which is dominated by propagation of the
      scintillation photons in the detector block. This study was intended to establish
      a Monte Carlo simulation-based evaluation tool taking into account the
      propagation of scintillation photons to estimate the intrinsic spatial and energy
      resolutions of the position-sensitive scintillator block in a SPECT detector.
      METHODS: We employed Geant4 Monte Carlo simulation library which incorporated the
      optical photon processes for two different designs of the position-sensitive
      scintillator blocks. The validation of the simulation code was performed for a
      monolithic NaI(Tl) scintillator (251 * 147 * 6.4 mm(3)) coupled to 15 flat-panel
      type multi-anode photo multiplier tubes (PMT) (H8500: Hamamatsu) and results were
      compared with those obtained experimentally. The code was then applied to a
      LaBr(3)(Ce) scintillator of 120 mm square with varied thicknesses for designing
      high-resolution detector. RESULTS: The simulation resulted in 2.6 mm full width
      at half maximum (FWHM) of spatial resolution and 9.0% FWHM of energy resolution
      for the NaI(Tl)-based detector, which were in a good agreement of the
      experimental results, i.e., 2.7 mm and 10%, respectively. These findings suggest
      that Geant4 simulation including optical photon processes enables to predict the
      spatial and energy resolutions of a SPECT detector block accurately. The
      simulation also demonstrated that 2 mm spatial resolution can be obtained for a 6
      mm thickness of the LaBr(3)(Ce), which is a significant improvement in
      performance as compared to existing gamma camera system that employs the
      scintillation detector fitted with PMTs. CONCLUSIONS: The Monte Carlo simulation
      based evaluation tool was established to estimate the intrinsic spatial and
      energy resolutions of SPECT detector with position sensitive PMTs. This
      simulation may be useful to provide an optimal design of a SPECT detector without
      physical experiments.

PMID- 22160743
TI  - Audiovisual interactions depend on context of congruency.
AB  - In this study, we addressed how the particular context of stimulus congruency
      influences audiovisual interactions. We combined an audiovisual congruency task
      with a proportion-of-congruency manipulation. In Experiment 1, we demonstrated
      that the perceived duration of a visual stimulus is modulated by the actual
      duration of a synchronously presented auditory stimulus. In the following
      experiments, we demonstrated that this crossmodal congruency effect is modulated
      by the proportion of congruent trials between (Exp. 2) and within (Exp. 4)
      blocks. In particular, the crossmodal congruency effect was reduced in the
      context with a high proportion of incongruent trials. This effect was attributed
      to changes in participants' control set as a function of the congruency context,
      with greater control applied in the context where the majority of the trials were
      incongruent. These data contribute to the ongoing debate concerning crossmodal
      interactions and attentional processes. In sum, context can provide a powerful
      cue for selective attention to modulate the interaction between stimuli from
      different sensory modalities.

PMID- 22160739
TI  - Metachronous liver metastasis from early gastric cancer.
AB  - INTRODUCTION: Early gastric cancer (EGC) has an excellent prognosis, but tumors
      recur in some patients even after apparently successful treatment. Among
      recurrent sites, the liver is one of the most common. In this study, we
      investigated clinicopathological features and factors predicting the development
      of liver metastasis from EGC. PATIENTS AND METHODS: We examined the medical
      records of 2,707 consecutive patients who underwent open gastrectomy for EGC
      (pT1; m, sm) between 1991 and 2005. We assessed clinicopathological features and
      predictive factors for EGC metastasis in the liver. RESULTS: Fifteen (0.6%) of
      the 2,707 patients developed liver metastasis. All primary gastric tumors of
      patients with liver recurrence demonstrated invasion to the submucosal layer.
      Macroscopically, nine patients had elevated-type and six depressed-type. Nodal
      metastasis was documented in seven patients (47%). Lymphatic and vascular
      involvements were seen in 11 (73%) and 7 (47%) patients, respectively.
      Multivariate analysis of patients with submucosal invasion revealed macroscopic
      elevated type and vascular involvement to be independent risk factors for liver
      metastasis. CONCLUSIONS: With submucosal cancer, the macroscopic elevated type
      and vascular involvement are significant predictive factors for EGC recurrence in
      the liver.

PMID- 22160744
TI  - Clinical indications and determinants of the rise of cesarean section in three
      hospitals in rural China.
AB  - This study investigated changes in cesarean delivery rate and cesarean
      indications in 3 county-level hospitals in rural China. Hospital delivery records
      in 1997 and 2003 were used to examine the reasons behind the changes. In Chengde
      County Hospital, the cesarean delivery rate increased from 28% in 1997 to 54% in
      2003. The rate increased from 43% in 1997 to 65% in 2003 in Anxian County
      Hospital and Anxian Maternal and Child Health Hospital. The dramatic increase in
      cesarean delivery in the study hospitals was associated with a shift from more
      severe to mild or no clinical indications. The ratio of mild to moderate to
      severe hypertension increased substantially. More than half of the cephalopelvic
      disproportion cases were diagnosed prior to labor. The majority of nuchal cord
      cases were diagnosed without fetal distress. Maternal/family request was the
      number one cesarean indication in Anxian County Hospital and Anxian MCH Hospital
      in 2003. Ultrasound evidence of nuchal cord moved from the ninth ranked
      indication in 1997 to the second in 2003 in Chengde County Hospital.

PMID- 22160745
TI  - Corrosion properties of S-phase layers formed on medical grade austenitic
      stainless steel.
AB  - The corrosion properties of S-phase surface layers formed in AISI 316LVM (ASTM
      F138) and High-N (ASTM F1586) medical grade austenitic stainless steels by plasma
      surface alloying with nitrogen (at 430 degrees C), carbon (at 500 degrees C) and
      both carbon and nitrogen (at 430 degrees C) has been investigated. The corrosion
      behaviour of the S-phase layers in Ringer's solutions was evaluated using
      potentiodynamic and immersion corrosion tests. The corrosion damage was evaluated
      using microscopy, hardness testing, inductive coupled plasma mass spectroscopy
      and X-ray diffraction. The experimental results have demonstrated that low
      temperature nitriding, carburising and carbonitriding can improve the localised
      corrosion resistance of both industrial and medical grade austenitic stainless
      steels as long as the threshold sensitisation temperature is not reached.
      Carburising at 500 degrees C has proved to be the best hardening treatment with
      the least effect on the corrosion resistance of the parent alloy.

PMID- 22160746
TI  - Gelatin-based anionic hydrogel as biocompatible substrate for human keratinocyte
      growth.
AB  - Ionic hydrogels are biocompatible candidates for skin tissue engineering. Two
      hydrogels synthesized by crosslinking gelatin with polylysine (positively charged
      HG1) or polyglutamic acid (negatively charged HG2) were tested using
      spontaneously immortalized human keratinocytes (HaCaT). HaCaT cells displayed
      higher adhesion and proliferation onto HG2, forming a continuous and stratified
      epithelium after 7 days. Moreover HaCaT cells grown onto HG2 showed a decreased
      Epilysin and Filaggrin expression, while transglutaminase-1 expression was
      increased. Those data indicate that human keratinocyte can form a stratified
      epithelium onto HG2 that could therefore be an useful tool for skin tissue
      engineering.

PMID- 22160747
TI  - Incorporating what promotoras learn: becoming role models to effect positive
      change.
AB  - Promotoras (community health workers) play an important health promotion role and
      must be continuously trained, but little is known about how much of their
      learning they actually put into practice. This non-randomized, longitudinal study
      examined knowledge and home environmental outcomes of an asthma and healthy homes
      training offered to promotoras using a train-the-trainer model. Eighty-five
      promotoras received the training and pre- and post-test surveys were used to
      measure training outcomes. Results showed a statistically significant increase in
      asthma and healthy home-related knowledge (P < .001). At 12-months post
      intervention, a majority of the promotoras (69%) reported they made household
      changes to improve their indoor environment as a result of the training. This
      study suggests that effective trainings can improve promotoras knowledge and
      behaviors for the promotion of healthy homes in the community. Further evaluation
      is needed to investigate whether these trainings allow promotoras to serve as
      role models within their communities "by educating through example" and thereby
      enhance their credibility as health educators.

PMID- 22160748
TI  - Preconditioning with a novel metallopharmaceutical NO donor in anesthetized rats
      subjected to brain ischemia/reperfusion.
AB  - Rut-bpy is a novel nitrosyl-ruthenium complex releasing NO into the vascular
      system. We evaluated the effect of Rut-bpy (100 mg/kg) on a rat model of brain
      stroke. Forty rats were assigned to four groups (Saline solution [SS], Rut-bpy,
      SS+ischemia-reperfusion [SS+I/R] and Rut-bpy+ischemia-reperfusion [Rut-bpy+I/R])
      with their mean arterial pressure (MAP) continuously monitored. The groups were
      submitted (SS+I/R and Rut-bpy+I/R) or not (SS and Rut-bpy) to incomplete global
      brain ischemia by occlusion of the common bilateral carotid arteries during 30
      min followed by reperfusion for further 60 min. Thirty minutes before ischemia,
      rats were treated pairwise by intraperitoneal injection of saline solution or Rut
      bpy. At the end of experiments, brain was removed for triphenyltetrazolium
      chloride staining in order to quantify the total ischemic area. In a subset of
      rats, hippocampus was obtained for histopathology scoring, nitrate and nitrite
      measurements, immunostaining and western blotting of the nuclear factor- kappaB
      (NF-kappaB). Rut-bpy pre-treatment decreased MAP variations during the transition
      from brain ischemia to reperfusion and decreased the fractional injury area. Rut
      bpy pre-treatment reduced NF-kappaB hippocampal immunostaining and protein
      expression with improved histopathology scoring as compared to the untreated
      operated control. In conclusion, Rut-bpy improved the total brain infarction area
      and hippocampal neuronal viability in part by inhibiting NF-kappaB signaling and
      helped to stabilize the blood pressure during the transition from ischemia to
      reperfusion.

PMID- 22160749
TI  - Anaesthesia of farmed fish: implications for welfare.
AB  - During their life cycle as farmed animals, there are several situations in which
      fish are subjected to handling and confinement. Netting, weighing, sorting,
      vaccination, transport and, at the end, slaughter are frequent events under
      farming conditions. As research subjects, fish may also undergo surgical
      procedures that range from tagging, sampling and small incisions to invasive
      procedures. In these situations, treatment with anaesthetic agents may be
      necessary in order to ensure the welfare of the fish. The main objective of this
      paper is to review our knowledge of the effects of anaesthetic agents in farmed
      fish and their possible implications for welfare. As wide variations in response
      to anaesthesia have been observed both between and within species, special
      attention has been paid to the importance of secondary factors such as body
      weight, water temperature and acute stress. In this review, we have limited
      ourselves to the anaesthetic agents such as benzocaine, metacaine (MS-222),
      metomidate hydrochloride, isoeugenol, 2-phenoxyethanol and quinaldine.
      Anaesthetic protocols of fish usually refer to one single agent, whereas
      protocols of human and veterinary medicine cover combinations of several drugs,
      each contributing to the effects needed in the anaesthesia. As stress prior to
      anaesthesia may result in abnormal reactions, pre-anaesthetic sedation is
      regularly used in order to reduce or avoid stress and is an integral part of the
      veterinary protocols of higher vertebrates. Furthermore, the anaesthetic agents
      that are used in order to obtain general anaesthesia are combined with analgesic
      agents that target nociception. The increased use of such combinations in fish is
      therefore included as a special section. Anaesthetic agents are widely used to
      avoid stress during various farming procedures. While several studies report that
      anaesthetics are effective in reducing the stress associated with confinement and
      handling, there are indications that anaesthesia may in itself induce a stress
      response, measured by elevated levels of cortisol. MS-222 has been reported to
      elicit high cortisol release rates immediately following exposure, while
      benzocaine causes a bimodal response. Metomidate has an inhibitory effect on
      cortisol in fish and seems to induce the lowest release of cortisol of the agents
      reported in the literature. Compared to what is observed following severe
      stressors such as handling and confinement, the amount of cortisol released in
      response to anaesthesia appears to be low but may represent an extra load under
      otherwise stressful circumstances. Furthermore, anaesthetics may cause secondary
      adverse reactions such as acidosis and osmotic stress due to respiratory arrest
      and insufficient exchange of gas and ions between the blood and the water. All in
      all, anaesthetics may reduce stress and thereby improve welfare but can also have
      unwanted side effects that reduce the welfare of the fish and should therefore
      always be used with caution. Finally, on the basis of the data reported in the
      literature and our own experience, we recommend that anaesthetic protocols should
      always be tested on a few fish under prevailing conditions in order to ensure an
      adequate depth of anaesthesia. This recommendation applies whether a single agent
      or a combination of agents is used, although it appears that protocols comprising
      combinations of agents provide wider safety margins. The analgesic effects of
      currently used agents, in spite of their proven local effects, are currently
      being debated as the agents are administrated to fish via inhalation rather than
      locally at the target site. We therefore recommend that all protocols of
      procedures requiring general anaesthesia should be complemented by administration
      of agents with analgesic effect at the site of tissue trauma.

PMID- 22160750
TI  - Capsicum annuum L. trypsin inhibitor as a template scaffold for new drug
      development against pathogenic yeast.
AB  - A 6,000 Da peptide, named CaTI, was isolated from Capsicum annuum L. seeds and
      showed potent inhibitory activity against trypsin and chymotrypsin. The aim of
      this study was to determine the effect of CaTI on Saccharomyces cerevisiae,
      Candida albicans, Candida tropicalis and Kluyveromyces marxiannus cells. We
      observed that CaTI inhibited the growth of S. cerevisiae, K. marxiannus as well
      as C. albicans and induced cellular agglomeration and the release of cytoplasmic
      content. No effect on growth was observed in C. tropicalis but morphological
      changes were noted. In the spot assay, different degrees of sensitivity were
      shown among the strains and concentrations tested. Scanning electron microscopy
      showed that S. cerevisiae, K. marxiannus and C. albicans, in the presence of
      CaTI, exhibited morphological alterations, such as the formation of pseudohyphae,
      cellular aggregates and elongated forms. We also show that CaTI induces the
      generation of nitric oxide and interferes in a dose-dependent manner with glucose
      stimulated acidification of the medium mediated by H(+)-ATPase of S. cerevisiae
      cells.

PMID- 22160751
TI  - Long-term efficacy of autologous haematopoietic stem cell transplantation in
      multiple sclerosis at a single institution in China.
AB  - Autologous haematopoietic stem cell transplantation (AHSCT) is a promising
      treatment for multiple sclerosis (MS) patients who have not adequately responded
      to conventional therapies. We retrospectively evaluated the safety and long-term
      clinical outcome of AHSCT in MS patients in China. Twenty-five patients with
      various types of MS were treated with AHSCT. Peripheral blood stem cells were
      derived by leukapheresis after mobilized with granulocyte colony-stimulating
      factor. Then CD34+ cell selection of the graft was performed and anti-thymocyte
      globulin was given for T-cell depletion, with the conditioning regimen BEAM
      adopted and early and late toxicities recorded. Long-term responses were
      evaluated by the expanded disability status scale (EDSS), progression-free
      survival and gadolinium-enhanced magnetic resonance imaging scans. 10, 7 and 8
      patients experienced neurological improvement, stabilization and progression,
      respectively. The median EDSS scores observed over 1-year follow-up after
      transplantation (5.5-7.0) were consistently lower than the baseline (8.0). The
      progression-free survival rate was 74, 65 and 48% at 3, 6 and 9 years post
      transplant. 58% cases (7/12) had active lesions at baseline and all turned to
      inactive status in the years of follow-up. 25% cases (3/12) experienced
      progression after transplantation but had no active lesions in MRI over the whole
      follow-up period. 17% cases (2/12) without active lesions at baseline progressed
      active lesions in MRI. The major early toxicity resulted in fever and late
      toxicity caused transplantation-related mortality due to severe pneumonia and
      varicella-zoster virus hepatitis, respectively. AHSCT is a feasible treatment for
      severe MS and its long-term efficacy is favorable.

PMID- 22160752
TI  - A modeling study of the responses of the lateral superior olive to ipsilateral
      sinusoidally amplitude-modulated tones.
AB  - The lateral superior olive (LSO) is a brainstem nucleus that is classically
      understood to encode binaural information in high-frequency sounds. Previous
      studies have shown that LSO cells are sensitive to envelope interaural time
      difference in sinusoidally amplitude-modulated (SAM) tones (Joris and Yin, J
      Neurophysiol 73:1043-1062, 1995; Joris, J Neurophysiol 76:2137-2156, 1996) and
      that a subpopulation of LSO neurons exhibit low-threshold potassium currents
      mediated by Kv1 channels (Barnes-Davies et al., Eur J Neurosci 19:325-333, 2004).
      It has also been shown that in many LSO cells the average response rate to
      ipsilateral SAM tones decreases with modulation frequency above a few hundred
      Hertz (Joris and Yin, J Neurophysiol 79:253-269, 1998). This low-pass feature is
      not directly inherited from the inputs to the LSO since the response rate of
      these input neurons changes little with increasing modulation frequency. In the
      current study, an LSO cell model is developed to investigate mechanisms
      consistent with the responses described above, notably the emergent rate decrease
      with increasing frequency. The mechanisms explored included the effects of after
      hyperpolarization (AHP) channels, the dynamics of low-threshold potassium
      channels (KLT), and the effects of background inhibition. In the model, AHP
      channels alone were not sufficient to induce the observed rate decrease at high
      modulation frequencies. The model also suggests that the background inhibition
      alone, possibly from the medial nucleus of the trapezoid body, can account for
      the small rate decrease seen in some LSO neurons, but could not explain the large
      rate decrease seen in other LSO neurons at high modulation frequencies. In
      contrast, both the small and large rate decreases were replicated when KLT
      channels were included in the LSO neuron model. These results support the
      conclusion that KLT channels may play a major role in the large rate decreases
      seen in some units and that background inhibition may be a contributing factor, a
      factor that could be adequate for small decreases.

PMID- 22160753
TI  - Sound-evoked olivocochlear activation in unanesthetized mice.
AB  - Genetic tools available for the mouse make it a powerful model to study the
      modulation of cochlear function by descending control systems. Suppression of
      distortion product otoacoustic emission (DPOAE) amplitude by contralateral
      acoustic stimulation (CAS) provides a robust tool for noninvasively monitoring
      the strength of descending modulation, yet investigations in mice have been
      performed infrequently and only under anesthesia, a condition likely to reduce
      olivocochlear activation. Here, we characterize the contralateral olivocochlear
      reflex in the alert, unanesthetized mouse. Head-fixed mice were restrained
      between two closed acoustic systems, while an artifact rejection protocol
      minimized contamination from self-generated sounds and movements. In mice
      anesthetized with pentobarbital, ketamine or urethane, CAS at 80 dB SPL evoked,
      on average, a <1-dB change in DPOAE amplitude. In contrast, the mean CAS-induced
      DPOAE suppression in unanesthetized mice was nearly 8 dB. Experiments in mice
      with targeted deletion of the alpha9 subunit of the nicotinic acetylcholine
      receptor confirmed the contribution of the medial olivocochlear efferents to this
      phenomenon. These findings demonstrate the utility of the CAS assay in the
      unanesthetized mouse and highlight the adverse effects of anesthesia when probing
      the functional status of descending control pathways within the auditory system.

PMID- 22160754
TI  - Effects of the rate of formant-frequency variation on the grouping of formants in
      speech perception.
AB  - How speech is separated perceptually from other speech remains poorly understood.
      Recent research suggests that the ability of an extraneous formant to impair
      intelligibility depends on the modulation of its frequency, but not its
      amplitude, contour. This study further examined the effect of formant-frequency
      variation on intelligibility by manipulating the rate of formant-frequency
      change. Target sentences were synthetic three-formant (F1 + F2 + F3) analogues of
      natural utterances. Perceptual organization was probed by presenting stimuli
      dichotically (F1 + F2C + F3C; F2 + F3), where F2C + F3C constitute a competitor
      for F2 and F3 that listeners must reject to optimize recognition. Competitors
      were derived using formant-frequency contours extracted from extended passages
      spoken by the same talker and processed to alter the rate of formant-frequency
      variation, such that rate scale factors relative to the target sentences were 0,
      0.25, 0.5, 1, 2, and 4 (0 = constant frequencies). Competitor amplitude contours
      were either constant, or time-reversed and rate-adjusted in parallel with the
      frequency contour. Adding a competitor typically reduced intelligibility; this
      reduction increased with competitor rate until the rate was at least twice that
      of the target sentences. Similarity in the results for the two amplitude
      conditions confirmed that formant amplitude contours do not influence across
      formant grouping. The findings indicate that competitor efficacy is not tuned to
      the rate of the target sentences; most probably, it depends primarily on the
      overall rate of frequency variation in the competitor formants. This suggests
      that, when segregating the speech of concurrent talkers, differences in speech
      rate may not be a significant cue for across-frequency grouping of formants.

PMID- 22160755
TI  - Integrin-epigenetics: a system with imperative impact on cancer.
AB  - Integrin-associated signaling is a crucial signaling network in mammalian cells.
      Thousands of molecules are involved in this signaling network. For example, the
      RTK, Src-family kinase, Ras, Wnt-, Notch-, and Raft/caveolae-mediated signaling
      pathways are related to integrin signaling. Integrin signaling is also associated
      with direct involvement of lipid rafts. Tumor formation, angiogenesis,
      metastasis, and attachment to distant tissues are largely associated with
      integrin signaling. Recent evidence has indicated that integrin expression and
      its functions are tightly regulated by epigenetic mechanisms (modifications of
      DNA and histones). Aberrations in these epigenetic regulation patterns are
      frequently associated with the development of various diseases, including cancer.
      In this review, we discuss influences of integrin signaling along with their
      epigenetic relationship on other signals of a normal functioning cell and its
      dysregulation in cancer.

PMID- 22160756
TI  - Analysis and validation of putative substances involved in fatal poisonings.
AB  - Each year, poison control centers throughout the United States respond to over 4
      million calls for help in treating individuals exposed to toxic substances.
      Although most cases develop no or minimal clinical effects, a small proportion of
      patients who receive medical care for overdoses with poison center consultation
      expire. When such cases are investigated by a medical examiner, the postmortem
      toxicology results may show substances other than those considered in the
      consultation with the poison center. We sought to determine the characteristics
      of discordance in fatal cases between the toxic substances reported to a regional
      poison control center and postmortem toxicology results. We conducted a
      retrospective study of the New Jersey regional poison control center records of
      all fatal cases between the years 1986 and 2006. Substances reported as putative
      agents to the poison center were compared to the postmortem toxicology results
      obtained by the medical examiner. The frequencies and characteristics surrounding
      discordance were examined. Of the 708 fatal cases reported to our poison center
      within the study period, complete postmortem toxicological evaluations were
      available for 206 (29.0%). Comparison of putative agents between information
      obtained by history and at postmortem evaluation showed discordance in 41
      (19.9%). In a substantial number of fatal cases receiving poison center
      consultation, substances were found at the time of postmortem examination that
      were not considered in the poison center consultation. The reasons for this
      discordance may include a lack of thorough history-taking or a cognitive bias to
      the substances initially reported.

PMID- 22160757
TI  - Prediction of drug response and safety in clinical practice.
AB  - Many clinicians hoped that the completion of the Human Genome Project would
      result in "individualized drug therapy," i.e., determining the right medication
      at the right dose 100% of the time based upon the individual's genetics. The
      pharmacogenomic prediction of drug efficacy and safety has not become a reality
      due to continuing realization of the complexity dictating the human-drug
      interaction. New methods of metabolomics, proteomics, and transcriptomics that
      account for this complexity hold promise for translational researchers hoping to
      increase drug efficacy and decrease drug toxicity.

PMID- 22160758
TI  - Hydrogen adsorption capacities of multi-walled boron nitride nanotubes and
      nanotube arrays: a grand canonical Monte Carlo study.
AB  - Hydrogen adsorption in multi-walled boron nitride nanotubes and their arrays was
      studied using grand canonical Monte Carlo simulation. The results show that
      hydrogen storage increases with tube diameter and the distance between the tubes
      in multi-walled boron nitride nanotube arrays. Also, triple-walled boron nitride
      nanotubes present the lowest level of hydrogen physisorption, double-walled boron
      nitride nanotubes adsorb hydrogen better when the diameter of the inner tube
      diameter is sufficiently large, and single-walled boron nitride nanotubes adsorb
      hydrogen well when the tube diameter is small enough. Boron nitride nanotube
      arrays adsorb hydrogen, but the percentage of adsorbed hydrogen (by weight) in
      boron nitride nanotube arrays is rather similar to that found in multi-walled
      boron nitride nanotubes. Also, when the Langmuir and Langmuir-Freundlich
      equations were fitted to the simulated data, it was found that multi-layer
      adsorptivity occurs more prominently as the number of walls and the tube diameter
      increase. However, in single-walled boron nitride nanotubes with a small
      diameter, the dominant mechanism is monolayer adsorptivity.

PMID- 22160759
TI  - The effect of annual surgical caseload on the rates of in-hospital pneumonia and
      other in-hospital outcomes after radical prostatectomy.
AB  - PURPOSE: To examine the effect of annual surgical caseload (ASC) on contemporary
      in-hospital pneumonia (IHP) rates and three other in-hospital outcomes after
      radical prostatectomy (RP). METHODS: Between 1999 and 2008, 34,490 open RPs were
      performed in the state of Florida. First, logistic regression models predicting
      the rate of IHP were fitted. Second, other logistic regression models examined
      the association between IHP and three other outcomes: in-hospital mortality,
      hospital charges within the highest quartile, and length of stay (LOS) within the
      highest quartile. Covariates included ASC, age, race, baseline Charlson
      Comorbidity Index (CCI), interval between admission and surgery, as well as blood
      transfusion. RESULTS: The overall IHP rate was 0.5%. It was higher in patients
      operated within the low (0.7%) and intermediate (0.5%) ASC tertile versus high
      ASC tertile (0.2%, P < 0.001). Mortality rate was 4.3% in IHP patients versus
      0.1% in others (P < 0.001). Median total hospital charges and median LOS were
      $55,350 versus $28,171 and 7 versus 3 days in IHP patients versus others,
      respectively (both P < 0.001). In multivariable analyses predicting IHP, the
      likelihood was 3.2-fold in patients operated by low ASC surgeons versus high ASC
      surgeons (P < 0.001). Second, in multivariable analyses, IHP patients were
      predisposed to 41-fold higher in-hospital mortality, were tenfold more likely to
      have total hospital charges >$37,333, and were 20-fold more likely to have a LOS
      >3 days (all P < 0.001). CONCLUSIONS: RP by high ASC surgeons exerts a protective
      effect on IHP rates. Additionally, IHP is associated with higher in-hospital
      mortality, prolonged LOS, and higher hospital charges.

PMID- 22160760
TI  - Lethal gallstone ileus.

PMID- 22160761
TI  - Mesenteric venous thrombosis.

PMID- 22160762
TI  - Smoking cessation and quality of life: changes in life satisfaction over 3 years
      following a quit attempt.
AB  - BACKGROUND: There has been limited research addressing changes in subjective well
      being as a result of quitting smoking. PURPOSE: The purpose of this study was to
      use longitudinal data to determine the relation between smoking cessation and
      subjective measures of well-being, including global quality of life (QOL), health
      related QOL (HR-QOL), affect, relationship satisfaction, and stressor occurrence.
      METHODS: As part of a randomized, placebo-controlled smoking cessation trial,
      1,504 participants (58.2% women, 83.9% white) completed assessments and had their
      smoking status biochemically confirmed at baseline and years 1 and 3 post-quit.
      RESULTS: Compared with continuing smokers, quitters showed improved global QOL,
      HR-QOL, and affect at years 1 and 3 and fewer stressors by year 3. Smoking status
      did not influence marital relationship satisfaction. CONCLUSIONS: Successful
      quitters, in contrast to continuing smokers, reported improved subjective well
      being, which could be used to motivate quit attempts by individuals with concerns
      about what life will be like without cigarettes.

PMID- 22160763
TI  - Junior doctors: the best kept secret in the NHS?

PMID- 22160764
TI  - Relationship between prenatal lead exposure and infant blood lead levels.
AB  - Recent literature has shown that analyzing newborn dried blood spots (DBS) may be
      effective in assessing some prenatal environmental exposures, such as exposure to
      lead. The purpose of this study was to evaluate the relationship between prenatal
      exposure to lead (as measured by newborn DBS results) and blood lead levels
      (BLLs) in infants 6 months of age or younger, using public health registry data
      for infants born in Texas from July 2002 through July 2006. The Texas Child Lead
      Registry (TCLR) was used to identify infants with documented elevated BLLs of 10
      MUg/dL or higher as well as infants with documented low BLLs. BLLs for these
      children were compared to their corresponding newborn DBS results using Pearson
      correlation coefficients and exact logistic regression models. Overall, a
      significant but weak positive correlation was found between infant BLLs and
      corresponding newborn DBS lead levels (r = 0.48). However, the odds of an infant
      with an elevated newborn DBS lead level having an elevated BLL at 6 months of age
      or younger were much greater than for an infant with a low newborn DBS lead level
      of <5 MUg/dL (adjusted odds ratio 27.95, 95% CI: 5.52-277.28). Although an
      association was observed between newborn DBS lead levels and BLLs in infants
      tested between 0 to 6 months of age, our findings suggest that prenatal exposure
      may not be the only significant source of lead exposure for infants <=6 months of
      age.

PMID- 22160766
TI  - ALF--a simulation framework for genome evolution.
AB  - In computational evolutionary biology, verification and benchmarking is a
      challenging task because the evolutionary history of studied biological entities
      is usually not known. Computer programs for simulating sequence evolution in
      silico have shown to be viable test beds for the verification of newly developed
      methods and to compare different algorithms. However, current simulation packages
      tend to focus either on gene-level aspects of genome evolution such as character
      substitutions and insertions and deletions (indels) or on genome-level aspects
      such as genome rearrangement and speciation events. Here, we introduce Artificial
      Life Framework (ALF), which aims at simulating the entire range of evolutionary
      forces that act on genomes: nucleotide, codon, or amino acid substitution (under
      simple or mixture models), indels, GC-content amelioration, gene duplication,
      gene loss, gene fusion, gene fission, genome rearrangement, lateral gene transfer
      (LGT), or speciation. The other distinctive feature of ALF is its user-friendly
      yet powerful web interface. We illustrate the utility of ALF with two possible
      applications: 1) we reanalyze data from a study of selection after globin gene
      duplication and test the statistical significance of the original conclusions and
      2) we demonstrate that LGT can dramatically decrease the accuracy of two well
      established orthology inference methods. ALF is available as a stand-alone
      application or via a web interface at http://www.cbrg.ethz.ch/alf.

PMID- 22160767
TI  - Nonallelic gene conversion is not GC-biased in Drosophila or primates.
AB  - Gene conversion is the unidirectional transfer of genetic information between
      allelic (orthologous) or nonallelic (paralogous) DNA segments. Recently, there
      has been much interest in understanding how gene conversion shapes the nucleotide
      composition of the genomic landscape. A widely held hypothesis is that gene
      conversion is universally GC-biased. However, direct experimental evidence of
      this hypothesis is limited to a single study of meiotic crossovers in yeast.
      Although there have been a number of indirect studies of gene conversion,
      evidence of GC-biased replacements gathered from such studies can also be
      attributed to positive selection, which has the same evolutionary dynamics as
      biased gene conversion. Here, we apply a direct phylogenetic approach to examine
      nucleotide replacements produced by nonallelic gene conversion in Drosophila and
      primate genomes. We find no evidence for GC-biased gene conversion in either
      lineage, suggesting that previously observed GC biases may be due to positive
      selection rather than to biased gene conversion.

PMID- 22160768
TI  - Does history repeat itself? Wavelets and the phylodynamics of influenza A.
AB  - Unprecedented global surveillance of viruses will result in massive sequence data
      sets that require new statistical methods. These data sets press the limits of
      Bayesian phylogenetics as the high-dimensional parameters that comprise a
      phylogenetic tree increase the already sizable computational burden of these
      techniques. This burden often results in partitioning the data set, for example,
      by gene, and inferring the evolutionary dynamics of each partition independently,
      a compromise that results in stratified analyses that depend only on data within
      a given partition. However, parameter estimates inferred from these stratified
      models are likely strongly correlated, considering they rely on data from a
      single data set. To overcome this shortfall, we exploit the existing Monte Carlo
      realizations from stratified Bayesian analyses to efficiently estimate a
      nonparametric hierarchical wavelet-based model and learn about the time-varying
      parameters of effective population size that reflect levels of genetic diversity
      across all partitions simultaneously. Our methods are applied to complete genome
      influenza A sequences that span 13 years. We find that broad peaks and trends, as
      opposed to seasonal spikes, in the effective population size history distinguish
      individual segments from the complete genome. We also address hypotheses
      regarding intersegment dynamics within a formal statistical framework that
      accounts for correlation between segment-specific parameters.

PMID- 22160769
TI  - Constructing instruction for struggling writers: what and how.
AB  - To respond to the articles in the current issue, I begin with an amalgamated
      conception of a transactional universe of reciprocal reading and composing
      processes that includes cognitive and social processes. Next, I situate the four
      studies in the current issue according to their epistemological emphases in the
      transactional conception. Three focal epistemological questions are framed as a
      way of situating each study: (a) what knowledge or processes do researchers
      emphasize most in the universe of composing processes? (b) Where do the
      researchers think that knowledge or those processes reside(s)? (c) How does one
      get or create that knowledge or those processes? Next, beneficial contributions
      to the field from the four studies are highlighted, and finally, future research
      directions are suggested.

PMID- 22160770
TI  - Isolated interstitial nodal spaces may facilitate preferential solute and fluid
      mixing in the rat renal inner medulla.
AB  - Recent anatomic findings indicate that in the upper inner medulla of the rodent
      kidney, tubules, and vessels are organized around clusters of collecting ducts
      (CDs). Within CD clusters, CDs and some of the ascending vasa recta (AVR) and
      ascending thin limbs (ATLs), when viewed in transverse sections, form
      interstitial nodal spaces, which are arrayed at structured intervals throughout
      the inner medulla. These spaces, or microdomains, are bordered on one side by a
      single CD, on the opposite side by one or more ATLs, and on the other two sides
      by AVR. To study the interactions among these CDs, ATLs, and AVR, we have
      developed a mathematical compartment model, which simulates steady-state solute
      exchange through the microdomain at a given inner medullary level. Fluid in all
      compartments contains Na(+), Cl(-), urea and, in the microdomain, negative fixed
      charges that represent macromolecules (e.g., hyaluronan) balanced by Na(+). Fluid
      entry into AVR is assumed to be driven by hydraulic and oncotic pressures. Model
      results suggest that the isolated microdomains facilitate solute and fluid mixing
      among the CDs, ATLs, and AVR, promote water withdrawal from CDs, and consequently
      may play an important role in generating the inner medullary osmotic gradient.

PMID- 22160771
TI  - Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia
      reperfusion-induced kidney injury.
AB  - cGMP-dependent protein kinase (PKG) is a multifunctional protein. Whether PKG
      plays a role in ischemia-reperfusion-induced kidney injury (IRI) is unknown. In
      this study, using an in vivo mouse model of renal IRI, we determined the effect
      of renal IRI on kidney PKG-I levels and also evaluated whether overexpression of
      PKG-I attenuates renal IRI. Our studies demonstrated that PKG-I levels (mRNA and
      protein) were significantly decreased in the kidney from mice undergoing renal
      IRI. Moreover, PKG-I transgenic mice had less renal IRI, showing improved renal
      function and less tubular damage compared with their wild-type littermates.
      Transgenic mice in the renal IRI group had decreased tubular cell apoptosis
      accompanied by decreased caspase 3 levels/activity and increased Bcl-2 and Bag-1
      levels. In addition, transgenic mice undergoing renal IRI demonstrated reduced
      macrophage infiltration into the kidney and reduced production of inflammatory
      cytokines. In vitro studies showed that peritoneal macrophages isolated from
      transgenic mice had decreased migration compared with control macrophages. Taken
      together, these results suggest that PKG-I protects against renal IRI, at least
      in part through inhibiting inflammatory cell infiltration into the kidney,
      reducing kidney inflammation, and inhibiting tubular cell apoptosis.

PMID- 22160772
TI  - Persistent disruption of mitochondrial homeostasis after acute kidney injury.
AB  - While mitochondrial dysfunction is a pathological process that occurs after acute
      kidney injury (AKI), the state of mitochondrial homeostasis during the injury and
      recovery phases of AKI remains unclear. We examined markers of mitochondrial
      homeostasis in two nonlethal rodent AKI models. Myoglobinuric AKI was induced by
      glycerol injection into rats, and mice were subjected to ischemic AKI. Animals in
      both models had elevated serum creatinine, indicative of renal dysfunction, 24 h
      after injury which partially recovered over 144 h postinjury. Markers of proximal
      tubule function/injury, including neutrophil gelatinase-associated lipocalin and
      urine glucose, did not recover during this same period. The persistent
      pathological state was confirmed by sustained caspase 3 cleavage and evidence of
      tubule dilation and brush-border damage. Respiratory proteins NDUFB8, ATP
      synthase beta, cytochrome c oxidase subunit I (COX I), and COX IV were decreased
      in both injury models and did not recover by 144 h. Immunohistochemical analysis
      confirmed that COX IV protein was progressively lost in proximal tubules of the
      kidney cortex after ischemia-reperfusion (I/R). Expression of mitochondrial
      fission protein Drp1 was elevated after injury in both models, whereas the fusion
      protein Mfn2 was elevated after glycerol injury but decreased after I/R AKI. LC3
      I/II expression revealed that autophagy increased in both injury models at the
      later time points. Markers of mitochondrial biogenesis, such as PGC-1alpha and
      PRC, were elevated in both models. These findings reveal that there is persistent
      disruption of mitochondrial homeostasis and sustained tubular damage after AKI,
      even in the presence of mitochondrial recovery signals and improved glomerular
      filtration.

PMID- 22160773
TI  - 2-Hydroxyestradiol slows progression of experimental polycystic kidney disease.
AB  - Male gender is a risk factor for progression of polycystic kidney disease (PKD).
      17beta-Estradiol (E2) protects experimentally, but clinical use is limited by
      adverse effects. Novel E2 metabolites provide many benefits of E2 without
      stimulating the estrogen receptor, and thus may be safer. We hypothesized that E2
      metabolites are protective in a model of PKD. Studies were performed in male
      control Han:SPRD rats, and in cystic males treated with orchiectomy, 2
      methoxyestradiol, 2-hydroxyestradiol (2-OHE), or vehicle, from age 3 to 12 wk.
      Cystic rats exhibited renal functional impairment (~50% decrease in glomerular
      filtration and renal plasma flow rates, P < 0.05) and substantial cyst
      development (20.5 +/- 2.0% of cortex area). 2-OHE was the most effective in
      limiting cysts (6.0 +/- 0.7% of cortex area, P < 0.05 vs. vehicle-treated cystic
      rats) and preserving function, in association with suppression of proliferation,
      apoptosis, and angiogenesis markers. Downregulation of p21 expression and
      increased expression of Akt, the mammalian target of rapamycin (mTOR), and some
      of its downstream effectors were significantly reversed by 2-OHE. Thus, 2-OHE
      limits disease progression in a cystic rodent model. Mechanisms include reduced
      renal cell proliferation, apoptosis, and angiogenesis. These effects may be
      mediated, at least in part, by preservation of p21 and suppression of Akt and
      mTOR. Estradiol metabolites may represent a novel, safe intervention to slow
      progression of PKD.

PMID- 22160774
TI  - Transcriptional analysis of infiltrating T cells in kidney ischemia-reperfusion
      injury reveals a pathophysiological role for CCR5.
AB  - Although T cells have been shown to play a direct role in kidney ischemia
      reperfusion injury (IRI), little is known about the underlying mechanisms. We
      hypothesized that studying the transcriptional responses in kidney-infiltrating T
      cells would help elucidate novel therapeutic targets for kidney IRI. Unilateral
      renal pedicle clamping for 45 min was performed in male C57BL/6 mice, and CD3(+)
      T cells were isolated from the kidney and purified. Transcriptional activities of
      T cell were measured by array-based PCR compared between ischemic kidneys and
      contralateral nonischemic kidneys. Among total of 89 genes analyzed, 24, 22, 24,
      and 37 genes were significantly changed at 6 h, day 3, day 10, and day 28 after
      IRI. Genes associated with cytokines, chemokines, and costimulatory molecules
      were upregulated. Pathway analysis identified CC motif chemokine receptor 5
      (CCR5) as a candidate pathophysiological pathway. CCR5 upregulation was validated
      at the protein level, and CCR5 blockade improved renal function after kidney IRI.
      Using discovery techniques to identify transcriptional responses in purified
      kidney-infiltrating cells enabled the elucidation of novel mechanisms and
      therapeutic targets for IRI.

PMID- 22160775
TI  - Exposure to maternal overnutrition and a high-fat diet during early postnatal
      development increases susceptibility to renal and metabolic injury later in life.
AB  - Overnutrition during pre- and postnatal development both confer increased
      susceptibility to renal and metabolic risks later in life; however, whether they
      have an additive effect on the severity of renal and metabolic injury remains
      unknown. The present study tested the hypothesis that a combination of a pre- and
      postnatal diet high in fat/fructose would exacerbate renal and metabolic injury
      in male offspring later in life. Male offspring born to high fat/high-fructose
      fed mothers and fed a high-fat/high-fructose diet postnatally (HF-HF) had
      increased urine albumin excretion (450%), glomerulosclerosis (190%), and
      tubulointerstitial fibrosis (101%) compared with offspring born to mothers fed a
      standard diet and fed a standard diet postnatally (NF-NF). No changes in blood
      pressure or glomerular filtration were observed between any of the treatment
      groups. The HF-HF offspring weighed ~23% more than offspring born to mothers fed
      a high-fat/high-fructose diet and fed a normal diet postnatally (HF-NF), as well
      as offspring born to mothers fed a standard diet regardless of their postnatal
      diet. The HF-HF rats also had increased (and more variable) blood glucose levels
      over 12 wk of being fed a high-fat/high-fructose diet. A combination of exposure
      to a high-fat/high-fructose diet in utero and postnatally increased plasma
      insulin levels by 140% compared with NF-NF offspring. Our data suggest that the
      combined exposure to overnutrition during fetal development and early postnatal
      development potentiate the susceptibility to renal and metabolic disturbances
      later in life.

PMID- 22160776
TI  - Activation of renal angiotensin type 1 receptor contributes to the pathogenesis
      of progressive renal injury in a rat model of chronic cardiorenal syndrome.
AB  - Although chronic cardiac dysfunction is known to progressively exacerbate renal
      injury, a condition known as type 2 cardiorenal syndrome (CRS), the mechanism
      responsible is largely unknown. The present study was undertaken to clarify the
      mechanism of renal injury in rats with both unilateral nephrectomy (NX) and
      surgically induced myocardial infarction (MI), corresponding to a model of type 2
      CRS. Compared with a control group, rats with both MI and NX (MI+NX) exhibited
      progressive proteinuria during the experimental period (34 wk after MI surgery),
      whereas proteinuria was not observed in rats with MI alone and was moderate in
      rats with NX alone. The proteinuria in rats with MI+NX was associated with renal
      lesions such as glomerulosclerosis and infiltration of mononuclear cells and
      upregulation of the renal proinflammatory and -fibrotic cytokine and angiotensin
      II type 1a receptor (AT1aR) genes. In contrast, plasma renin activity was lowered
      in rats with MI+NX. Immunohistochemistry revealed that the increased AT1R protein
      was present mainly in renal interstitial mononuclear cells. Olmesartan medoxomil,
      an AT1R blocker, markedly reduced the proteinuria and infiltration of mononuclear
      cells, whereas spironolactone, a mineralocorticoid receptor blocker, did not. The
      present findings demonstrate the pathogenetic role of renal interstitial AT1R
      signaling in a model of type 2 CRS, providing evidence that AT1R blockade can be
      a useful therapeutic option for this syndrome.

PMID- 22160777
TI  - Functional consequences of inhibiting exocytosis of Weibel-Palade bodies in acute
      renal ischemia.
AB  - Exocytosis of Weibel-Palade bodies (WPB) represents a distinct response of
      endothelial cells to stressors, and local release of WPB contents leads to
      systemic escalation of this response. We synthesized a glycine-(Nalpha-Et)lysine
      proline-arginine (ITF 1697) peptide that has a potential to inhibit exocytosis of
      WPB and protect microcirculation. Here, we confirmed an inhibitory effect of ITF
      1697 using intravital videoimaging and point-tracking of individual organelles.
      In an in vivo study, mice were implanted with Alzet osmotic pumps (10 MUg ITF
      1697.kg(-1).min(-1) at volume of 1 MUl/h) and subjected to renal ischemia (IRI).
      IRI resulted in marked renal injury and elevation of serum creatinine in mice
      treated with a vehicle. In contrast, renal injury and elevation of creatinine
      were significantly ameliorated in mice subjected to IRI and receiving ITF 1697.
      ITF 1697 prevented a systemic response to IRI: a significant surge in the levels
      of eotaxin and IL-8 (KC; both components of WPB), IL-1alpha, IL-1beta, and RANTES
      was all prevented or blunted by the administration of ITF 1697, whereas the
      levels of an anti-inflammatory, IL-10, and macrophage inflammatory protein-1alpha
      were upregulated in ITF 1697-treated animals. En face staining of aortic
      endothelial cells showed that WPB were depleted after 40-180 min post-IRI, and
      this was significantly blunted in aortic preparations obtained from mice treated
      with ITF 1697. WPB exocytosis contributed to IRI-associated mobilization of
      endothelial progenitor cells and hematopoietic stem cells, and ITF 1697 blunted
      their mobilization. Unexpectedly, 1 mo after IRI, mice treated with ITF 1697
      showed a significantly more pronounced degree of scarring than nontreated
      animals. In conclusion, 1) application of ITF 1697 inhibits exocytosis of WPB and
      IRI; 2) the systemic inflammatory response of IRI is in part due to the
      exocytosis of WPB and its blockade blunts it; and 3) ITF 1697 improves short-term
      renal function after IRI, but not the long-term fibrotic complications.

PMID- 22160778
TI  - The laparoscopic approach to paraesophageal hernia repair.
AB  - INTRODUCTION: Laparoscopic paraesophageal hernia repair continues to be one of
      the most challenging procedures facing the minimally invasive surgeon.
      DISCUSSION: A thorough understanding of the tenets of the operation and advanced
      skills in minimally invasive laparoscopy are needed for long-term freedom from
      symptomatic and anatomic recurrence. These include complete reduction of the
      hernia sac from the mediastinum back into the abdomen with careful preservation
      of the integrity of muscle and peritoneal lining of the crura, aggressive and
      complete mobilization of the esophagus to the level of the inferior pulmonary
      vein, vagal preservation, clear identification of the gastroesophageal junction
      to allow accurate assessment of the intraabdominal esophageal length, and use of
      Collis gastroplasty when esophageal lengthening is required for a tension-free
      intraabdominal repair. Liberal mobilization of the phrenosplenic and
      phrenogastric attachments substantially increases the mobility of the left limb
      of the crura, allowing for a tension-free primary closure in a large percentage
      of patients. CONCLUSION: The following describes our current approach to
      laparoscopic paraesophageal hernia repair following a decade of refinement in a
      high-volume center.

PMID- 22160779
TI  - Public perception of LESS surgery and NOTES.
AB  - INTRODUCTION: This study was undertaken to determine public attitudes toward
      laparoendoscopic single-site (LESS) surgery and natural orifice transluminal
      endoscopic surgery (NOTES) and to determine how they are impacted by age, gender,
      and obesity. METHODS: One hundred fifty-two citizens completed a validated
      questionnaire. Pearson correlations were computed to determine relationships
      among items queried. Scores ranged from 1 (lowest) to 5 (highest) and are
      presented as median, mean +/- SD. RESULTS: The citizens generally liked their
      physique (4, 4 +/- 1.0) and felt attractive (4, 4 +/- 1.0). LESS surgery was
      appealing if it involved no more risk or recovery and none to minimally more
      pain, operative time, and cost. Older and heavier citizens were more interested
      in reduced risk, pain, and operative/recovery time and less interested in
      scarring/appearance. Thirty-nine percent would consider NOTES, though only with
      no more risk, pain, operative time, and cost (<$200). Older people regarded NOTES
      more favorably. Lack of scarring with NOTES was most important by only 32% of
      those participants that would consider undergoing a NOTES procedure. CONCLUSION:
      Acceptance of LESS surgery and NOTES depends upon no additional risk and no or
      minimally increased pain, recovery time, and cost. Improved cosmesis is not
      generally a priority, particularly in older or heavier people. Safety, pain, and
      recovery time remain major issues in deciding operative choices.

PMID- 22160781
TI  - Totally laparoscopic Billroth II gastrectomy with a novel, safe, simple, and time
      saving anastomosis by only stapling devices.
AB  - BACKGROUND: Totally laparoscopic gastrectomy represents the evolution of
      laparoscopy-assisted gastrectomy. Most surgeons prefer laparoscopy-assisted
      gastrectomy rather than totally laparoscopic procedures because of technical
      difficulties of intracorporeal anastomosis. We created one novel stapling
      anastomosis without hand-sewn technique in totally laparoscopic Billroth II
      gastrectomy. The feasibility and early surgical outcomes of totally laparoscopic
      Billroth II gastrectomy with stapling anastomosis and with hand-sewn anastomosis
      were introduced in this study. METHODS: We retrospectively analyzed early
      surgical outcomes in 70 patients who underwent totally laparoscopic Billroth II
      distal gastrectomy for gastric cancer between January 2010 and July 2011. The
      patients were divided into hand-sewn and device groups according to whether
      intracorporeal anastomosis was performed by only hand-sewn technique (n = 36) or
      only stapling devices (n = 34). In the device group, the gastrojejunostomy was
      performed using a circular stapler, and an additional side-to-side
      jejunojejunostomy was made at the site of jejunal enterotomy. RESULTS: There was
      no difference in the mean number of lymph nodes retrieved in both groups. The
      blood loss (hand-sewn group 205.8 +/- 37.4 vs. device group 201.2 +/- 51.2 ml, p
      > 0.05) and hospital stay (hand-sewn group 6.5 +/- 3.7 vs. device group 5.9 +/-
      4.1 days, p > 0.05) were similar in both groups. We found that intracorporeal
      anastomosis by totally stapling devices was associated with decreased operative
      time (hand-sewn group 239.0 +/- 40.1 vs. device group 203.6 +/- 27.9 min, p <
      0.05). CONCLUSION: We suggest that intracorporeal anastomosis using only stapling
      devices in the described method was as safe and feasible as by hand-sewn
      technique. Moreover, it is a simple and time-saving method without any difficult
      hand-sewn procedures.

PMID- 22160780
TI  - Neo-adjuvant chemoradiation therapy using S-1 followed by surgical resection in
      patients with pancreatic cancer.
AB  - OBJECTIVE: The aim of this study was to compare short-term surgical results in
      pancreatic cancer patients who underwent surgical resection after neo-adjuvant
      chemoradiation therapy (NACRT) using S-1. METHODS: The study population comprised
      77 patients with pancreatic cancer between 2006 and 2010. Out of 34 patients who
      underwent staging laparoscopy between 2008 and 2010, 31 patients without occult
      distant organ metastasis underwent chemoradiation and of whom 30 underwent
      pancreatectomy (NACRT group). Of the other 43 patients, 36 underwent surgical
      resection in 2006-2008, followed by adjuvant therapy (adjuvant group). The
      primary endpoint was frequency of pathological curative resection (R0). RESULTS:
      The new regimen of NACRT was feasible and safe. Twenty-eight of 30 (93%) patients
      in the NACRT group had R0 resection, which was significantly higher than in the
      adjuvant group (21 of 36 patients, 58%, p = 0.005). The number and extent of
      metastatic lymph nodes in the NACRT group (1 (0-25), N0/1; 18 of 38) was
      significantly lower than in the adjuvant group (2 (0-19), N0/1; 23 of 30), p =
      0.0363). The frequency of intractable ascites in the NACRT group (eight of 30)
      was significantly higher than in the adjuvant group (two of 36, p = 0.035).
      CONCLUSION: Neo-adjuvant chemoradiation therapy using S-1 followed by
      pancreatectomy can improve the rate of pathologically curative resection and
      reduces the number and extent of lymph node metastasis.

PMID- 22160782
TI  - Pancreatic neoplasms in pregnancy: diagnosis, complications, and management.
AB  - BACKGROUND: Neoplasms of the pancreas during pregnancy are rare, with less than
      25 cases of benign and malignant tumors reported in the literature. METHODS: We
      present three unique cases of pancreatic tumors occurring during pregnancy--one
      mucinous cystic neoplasm and two adenocarcinomas. We review the literature
      regarding pancreatic neoplasms during pregnancy and discuss the diagnosis,
      complications, and management of these tumors. RESULTS: Magnetic resonance
      imaging and ultrasound are the imaging modalities of choice in pregnancy. In
      patients with benign or premalignant tumors, surgical resection may be postponed
      until the second trimester. In symptomatic patients, or if there is a concern for
      intrauterine growth restriction, urgent surgical intervention should be
      performed. With malignant tumors, the benefit of delaying surgery must be
      balanced with the risk of maternal disease progression. Termination of the
      pregnancy should be discussed when a malignant tumor is diagnosed during the
      first trimester. Pancreatic tumors diagnosed during the third trimester may be
      resected after delivery. If malignant, early delivery of the fetus and subsequent
      maternal operation can be considered at appropriate fetal maturity. CONCLUSION:
      When these tumors occur during pregnancy, they present a diagnostic and treatment
      dilemma, with variation in treatment based on gestational age and patient
      preference.

PMID- 22160783
TI  - Encapsulation of Huh-7 cells within alginate-poly(ethylene glycol) hybrid
      microspheres.
AB  - Novel calcium alginate poly(ethylene glycol) hybrid microspheres (Ca-alg-PEG)
      were developed and evaluated as potentially suitable materials for cell
      microencapsulation. Grafting 5-13% of the backbone units of sodium alginate (Na
      alg) with alpha-amine-omega-thiol PEG maintained the gelling capacity in presence
      of calcium ions, while thiol end groups allowed for preparing chemically
      crosslinked hydrogel via spontaneous disulfide bond formation. The combination of
      these two gelling mechanisms yielded Ca-alg-PEG. Human hepatocellular carcinoma
      cells (Huh-7) were encapsulated in Ca-alg-PEG and calcium alginate beads (Ca
      alg), and cultured for 2 weeks under agitation conditions. Immediately after
      completion of the microencapsulation, the cell viability was 60% and similar in
      Ca-alg-PEG and Ca-alg. The proliferation of Huh-7 encapsulated in Ca-alg-PEG was
      slightly higher than in Ca-alg. Accelerated proliferation after 2 weeks was
      observed for the encapsulation in Ca-alg-PEG. The production of albumin confirmed
      the functionality of the encapsulated Huh-7 cells. The study confirms the
      suitability of Ca-alg-PEG and the one-step technology for cell
      microencapsulation.

PMID- 22160785
TI  - Response to an intervening event reverses nonspatial repetition effects in 2AFC
      tasks: nonspatial IOR?
AB  - The repetition effect in two-alternatiave forced choice (2AFC) tasks is a
      cornerstone effect in human cognition. Yet the experiments described here show
      that the customary benefit of repetition reverses to a cost of repetition when
      participants respond to an irrelevant event between targets. In Experiments 1A
      1C, participants made manual 2AFC decisions to both of two consecutive targets on
      a trial and, on some trials, also made a manual response to an intervening event
      that appeared between the two targets. A repetition benefit was observed when no
      intervening event appeared, whereas a repetition cost was observed when a
      response was required to an intervening event. Experiment 2 ruled out a solely
      strategic interpretation of the repetition cost effect observed on intervening
      event trials. In Experiments 3A and 3B, an intervening event that required a
      simple vocal "go" response also produced a repetition cost. In Experiment 4, a
      repetition cost was observed when the intervening event was changed to a tone
      presented aurally. In Experiment 5, the repetition benefit was observed when a
      response was withheld to an intervening event. A dual-process interpretation of
      these results is discussed, with one process related to episodic integration, and
      the other related to processes that produce inhibition of return.

PMID- 22160784
TI  - In vitro mannose trimming property of human ER alpha-1,2 mannosidase I.
AB  - Endoplasmic reticulum alpha-1,2 mannosidase I (ERManI) is an enzyme, which
      removes alpha(1-2) linked mannoses from asparagine-linked oligosaccharides on
      glycoproteins in the endoplasmic reticulum (ER). ERManI preferentially removes
      one alpha(1-2) linked mannose from B-chain of Man(9)GlcNAc(2). When glycoproteins
      fail to achieve properly folding, increased removal of alpha(1-2) linked mannoses
      on their oligosaccharides is induced and leads them to be disposed and degraded
      by ER-associated degradation pathway. However, it is still inconclusive whether
      accelerated removal of alpha(1-2) linked mannoses on those glycoproteins is
      catalyzed by the alpha-1,2 mannosidase I, proteins similar to mannosidase I [e.g.
      ER degradation-enhancing alpha-1,2 mannosidase-like protein (EDEM)], or both of
      them. Therefore, to approach this issue, we have investigated its in vitro
      activities using various oligosaccharides and glycoproteins as substrates. A
      recombinant form of human ERManI (hERManI) was prepared by using Escherichia
      coli. First, the enzyme generated Man(6)GlcNAc(2)-PA and Man(5)GlcNAc(2)-PA from
      100 MUM Man(9)GlcNAc(2)-PA after a one-hour reaction. Second, we have exposed
      bovine thyroglobulin and soybean agglutinin to denaturing conditions, e.g. 8 M
      urea, and used those glycoproteins as substrates. Sugar moieties were released
      from the reactant by PNGase F and their structures and amounts were elucidated by
      HPLC analysis. Intriguingly, the enzyme was shown to remove mannoses from bovine
      thyroglobulin and soybean agglutinin to larger extents when they were exposed to
      a denaturant. Therefore, our results suggested that hERManI could recognize
      tertiary and/or quaternary structures of glycoproteins and remove more alpha-1,2
      linked mannoses from misfolded glycoproteins in living cells.

PMID- 22160786
TI  - Partnerships for the design, conduct, and analysis of effectiveness, and
      implementation research: experiences of the prevention science and methodology
      group.
AB  - What progress prevention research has made comes through strategic partnerships
      with communities and institutions that host this research, as well as
      professional and practice networks that facilitate the diffusion of knowledge
      about prevention. We discuss partnership issues related to the design, analysis,
      and implementation of prevention research and especially how rigorous designs,
      including random assignment, get resolved through a partnership between community
      stakeholders, institutions, and researchers. These partnerships shape not only
      study design, but they determine the data that can be collected and how results
      and new methods are disseminated. We also examine a second type of partnership to
      improve the implementation of effective prevention programs into practice. We
      draw on social networks to studying partnership formation and function. The
      experience of the Prevention Science and Methodology Group, which itself is a
      networked partnership between scientists and methodologists, is highlighted.

PMID- 22160787
TI  - Increased placental growth factor in cerebrospinal fluid of patients with
      epilepsy.
AB  - Recent studies suggest that angiogenesis and vascular endothelial growth factor
      (VEGF) are involved in the pathophysiology of epilepsy. However, relatively
      little data are available linking placenta growth factor (PIGF) with epilepsy. In
      this study, we assessed concentrations of PIGF in cerebrospinal fluid (CSF) of 60
      epileptic patients and 24 non-seizure subjects using sandwich enzyme-linked
      immunosorbent assays. Epileptic patients in general had higher concentration of
      CSF-PIGF than controls (7.95 +/- 0.88 ng/l vs. 5.87 +/- 0.79 ng/l, P < 0.01). CSF
      PIGF level in secondary epileptic patients (8.59 +/- 1.26 ng/l) was higher than
      that in idiopathic epileptic patients (7.62 +/- 0.20 ng/l) (P < 0.05). In
      idiopathic epilepsy, CSF-PIGF level in patients with high seizure frequency was
      higher than those in patients with low seizure frequency and seizure-free in
      recent 3 years (7.78 +/- 0.23 ng/l vs. 7.49 +/- 0.09 ng/l and 7.59 +/- 0.10 ng/l,
      P < 0.05). Concentration of CSF-PIGF in patients with a disease duration of > 5
      years was higher than those in patients with durations of 1-5 years and <1 year
      (7.72 +/- 0.20 ng/l vs. 7.52 +/- 0.09 ng/l and 7.41 +/- 0.07 ng/l, P < 0.05).
      These results indicate that preexisting brain damage, seizure frequency and
      disease duration are important factors contributing to elevated PIGF.

PMID- 22160788
TI  - An analysis of content in comprehensive cancer control plans that address chronic
      hepatitis B and C virus infections as major risk factors for liver cancer.
AB  - Chronic hepatitis B and hepatitis C virus (HBV and HCV) infections are among the
      leading causes of preventable death worldwide. Chronic viral hepatitis is the
      cause of most primary liver cancer, which is the third leading cause of cancer
      deaths globally and the ninth leading cause of cancer deaths in the United
      States. The extent to which comprehensive cancer control (CCC) programs in
      states, tribal governments and organizations, territories, and Pacific Island
      jurisdictions address chronic hepatitis B and/or hepatitis C infections as risk
      factors for liver cancer or recommend interventions for liver cancer prevention
      in their CCC plans remains unknown. We searched CCC plans for this information
      using the search tool at http://www.cdc.gov/cancer/ncccp/ to access the content
      of plans for this information. A combination of key search terms including "liver
      cancer", "hepatitis", "chronic alcohol", and "alcohol abuse" were used to
      identify potential content regarding liver cancer risk factors and prevention.
      Relevant content was abstracted for further review and classification. Of 66
      (Although CDC funds 65 programs, one of the Pacific Island Jurisdiction grantees
      is the Federated States of Micronesia (FSM). This national program supports four
      FSM states, each of which submits a cancer plan to CDC for a total of 69 plans.
      During this time period, 66 plans were available on the website.) CCC plans, 27%
      (n = 18) addressed liver cancer using the above-mentioned search terms. In the 23
      plans that addressed HBV and/or HCV, there were 25 goals, objectives, strategies,
      and outcomes aimed at reducing the incidence or prevalence of HBV and/or HCV
      infection. While nearly a third of CCC programs identify at least one goal,
      objective, strategy, outcome, or prevention program to reduce cancer burden in
      their CCC plans, few plans discuss specific actions needed to reduce the burden
      of liver cancer.

PMID- 22160789
TI  - Lethal serotonin syndrome after methylone and butylone ingestion.
AB  - INTRODUCTION: A new generation of designer phenethylamines have emerged and
      aggressively marketed as "legal highs." The drugs are labeled "not for human
      consumption" to avoid widespread recognition and prosecution under the existing
      analog drug laws. The newest generation includes methylone and butylone.
      Methylone and butylone have minor structural changes and similar pharmacodynamics
      properties to scheduled drugs. CASE REPORT: We report a case of a healthy 24-year
      old who ingested a capsule containing methylone and butylone sold as "Ecstasy" at
      a concert. The patient presented to the emergency department, comatose febrile,
      tachycardic, tachypnic, and hypertensive. On exam, she was diaphoretic,
      tremulous, hyperreflexic, and had sustained clonus. The patient was aggressively
      cooled, and despite maximal supportive care, the patient progressed to multi
      system organ failure and ultimately expired. We obtained and analyzed both her
      urine and a capsule found on her person similar to the capsules ingested. In both
      samples, laboratory analysis identified only methylone and butylone. CONCLUSION:
      This is the first reported death for methylone or butylone and the first human or
      animal ingestion of butylone. Clinicians and public health officials should work
      together as new designer drugs emerge.

PMID- 22160790
TI  - Mechanistic insights into arterial repair with mesenchymal stromal cells :
      editorial to: "Stem cell therapy for arterial restenosis: potential parameters
      contributing to the success of bone marrow-derived mesenchymal stromal cells" by
      A. Forte et al.

PMID- 22160791
TI  - Across-channel timing differences as a potential code for the frequency of pure
      tones.
AB  - When a pure tone or low-numbered harmonic is presented to a listener, the
      resulting travelling wave in the cochlea slows down at the portion of the basilar
      membrane (BM) tuned to the input frequency due to the filtering properties of the
      BM. This slowing is reflected in the phase of the response of neurons across the
      auditory nerve (AN) array. It has been suggested that the auditory system
      exploits these across-channel timing differences to encode the pitch of both pure
      tones and resolved harmonics in complex tones. Here, we report a quantitative
      analysis of previously published data on the response of guinea pig AN fibres, of
      a range of characteristic frequencies, to pure tones of different frequencies and
      levels. We conclude that although the use of across-channel timing cues provides
      an a priori attractive and plausible means of encoding pitch, many of the most
      obvious metrics for using that cue produce pitch estimates that are strongly
      influenced by the overall level and therefore are unlikely to provide a
      straightforward means for encoding the pitch of pure tones.

PMID- 22160792
TI  - Ipsilateral hemiparesis and spontaneous horizontal nystagmus caused by middle
      cerebral artery territory infarct in a patient with agenesis of the corpus
      callosum.
AB  - Ipsilateral hemiparesis and spontaneous nystagmus have rarely been reported after
      a cerebral lesion. A 35-year-old man with agenesis of the corpus callosum
      developed ipsilateral hemiparesis and spontaneous horizontal nystagmus after an
      infarct in the right middle cerebral artery territory. Magnetic resonance imaging
      revealed the presence of an acute infarct in the right middle and inferior
      frontal gyrus, supramarginal gyrus, insular gyrus, internal capsule, head of
      caudate nucleus, putamen, and globus pallidus. Transcranial stimulation of the
      hand area of the cerebral motor cortex produced motor-evoked potentials in the
      abductor pollicis brevis muscle exclusively on the ipsilateral side. No motor
      evoked potentials were evoked in the abductor pollicis brevis muscle
      contralateral to the stimulation. The motor-evoked potentials and magnetic
      resonance imaging findings in our case suggest that anomalies of the decussation
      of the corticospinal tracts can be found in agenesis of the corpus callosum.

PMID- 22160793
TI  - Reversible progressive supranuclear palsy-like phenotype as an initial
      manifestation of HIV infection.
AB  - Movement disorders are common manifestations of human immunodeficiency virus
      (HIV) infection, and may sometimes be the initial manifestations of HIV
      infection. Although secondary progressive supranuclear palsy (PSP) due to factors
      such as paraneoplastic, vascular, and hypoxic-ischemic injury have been reported,
      PSP associated with HIV infection has received little attention. We describe a
      patient who displayed a progressive parkinsonian phenotype fulfilling the
      criteria for PSP over a period of a year. The parkinsonism was the initial
      manifestation of HIV infection and was eliminated by highly active antiretroviral
      therapy. This case report indicates that one should consider HIV infection as a
      cause of PSP-like parkinsonism.

PMID- 22160794
TI  - Molecular design of aminopolynitroazole-based high-energy materials.
AB  - The density functional theory (DFT) was employed to calculate the energetic
      properties of several aminopolynitroazoles. The calculations were performed to
      study the effect of amino and nitro substituents on the heats of formation,
      densities, detonation performances, thermal stabilities, and sensitivity
      characteristics of azoles. DFT-B3LYP, DFT-B3PW91, and MP2 methods utilizing the
      basis sets 6-31 G* and 6-311 G (2df, 3p) were adopted to predict HOFs via
      designed isodesmic reactions. All of the designed aminopolynitroazoles had heats
      of formation of >220 kJ mol(-1). The crystal densities of the
      aminopolynitroazoles were predicted with the cvff force field. All of the
      energetic azoles had densities of >1.83 g/cm(3). The detonation velocities and
      pressures were evaluated using the Kamlet-Jacobs equations, utilizing the
      predicted densities and heats of formation. It was found that
      aminopolynitroazoles have a detonation velocity of about 9.1 km/s and detonation
      pressure of 36 GPa. The bond dissociation energies for the C-NO(2) and N-NO(2)
      bonds were analyzed to investigate the stabilities of the designed molecules. The
      charge on the nitro group was used to assess impact sensitivity in the present
      study. The results obtained imply that the designed molecules are stable and are
      expected to be candidates for high-energy materials (HEMs).

PMID- 22160795
TI  - SWIFT MODELLER v2.0: a platform-independent GUI for homology modeling.
AB  - SWIFT MODELLER v2.0 is a platform-independent Java-based graphical user interface
      to MODELLER. It provides an interactive homology modeling solution by automating
      the formatting, scripting, and data extraction processes, meaning that the user
      only needs to paste in the protein target sequence as input. SWIFT MODELLER v2.0
      takes a step-by-step approach where the flow of the software screens depicts
      steps in the homology modeling protocol. Ramachandran plots and DOPE profile
      graphs are sketched and displayed for in-depth model analysis, along with an
      embedded Jmol viewer for 3D visualization of the constructed model. SWIFT
      MODELLER v2.0 is functional on all Linux-based and Microsoft Windows operating
      systems for which MODELLER has been developed. The software is available as
      freeware at http://www.bitmesra.ac.in/swift-modeller/swift.htm .

PMID- 22160796
TI  - Lack of evidence for increased level of circulating urothelial cells in the
      peripheral blood after transurethral resection of bladder tumors.
AB  - PURPOSE: Aggressive intervention against the bladder wall during transurethral
      resection of bladder tumors (TURBT) causes damage and leakage from blood vessels
      to the bladder lumen. The aim of this study was to determine whether TURBT could
      increase the level of circulating urothelial cells. METHODS: Expression of tumor
      markers, discriminative for nucleated blood cells and urothelium, was evaluated
      by quantitative (q) RT-PCR on RNA isolated from peripheral blood samples of 51
      patients who underwent TURBT for >=cT1c bladder tumors. RESULTS: Four of 14
      studied genes, epidermal growth factor receptor (EGFR), Collagen alpha-1(I)
      chain, Mast/stem cell growth factor receptor (KIT) and CD47, exhibited
      significant differences in gene expression between controls and cancer patients.
      While TURBT did not significantly increase the number of PCR-positive results of
      any transcripts, positive RT-PCR detection for EGFR was significantly less
      frequent on day 30 compared to results obtained before surgery. CONCLUSIONS:
      Although the results of our study do not provide evidence for increased tumor
      cell release into the peripheral blood after TURBT, they seem to indicate that
      EGFR mRNA measurement in the blood may provide useful information for urologists.

PMID- 22160798
TI  - Commentary: benefits of adherence to psychotropic medications on depressive
      symptoms and antiretroviral medication adherence among HIV-positive men and
      women.

PMID- 22160797
TI  - Relationship between amounts of daily cigarette consumption and abdominal obesity
      moderated by CYP2A6 genotypes in Chinese male current smokers.
AB  - BACKGROUND: Cigarette smoking is an important risk factor for abdominal obesity.
      However, the degree to which the CYP2A6 genotype moderates the relationship
      between smoking and abdominal obesity has not been established. PURPOSE: This
      study aims to investigate whether or not the relationship between smoking
      quantity and abdominal obesity is influenced by CYP2A6 genotypes. METHODS: Nine
      hundred fifty-four male current smokers were selected. A venous specimen was
      collected to test serum cotinine and CYP2A6 genotype, and all smokers were
      divided into heavy (>15 cigarettes/day) and light smokers (<=15 cigarettes/day).
      RESULTS: Heavy smoking increased the risk of abdominal obesity (odds ratio (OR) =
      1.57; 95% CI, 1.13-2.19) compared with light smoking. Furthermore, heavy smoking
      had a positive interactive effect with CYP2A6 poor metabolizer genotype on
      abdominal obesity (OR = 3.90; 95% CI, 1.25-12.18). Moreover, CYP2A6 poor
      metabolizer genotypes were associated with slower nicotine metabolism.
      CONCLUSIONS: Heavy smoking may increase the risk of abdominal obesity
      particularly in smokers with CYP2A6 poor metabolizer genotypes.

PMID- 22160799
TI  - A multi-factorial model for examining racial and ethnic disparities in acute
      asthma visits by children.
AB  - BACKGROUND: Causes of children's asthma health disparities are complex. Parents'
      asthma illness representations may play a role. PURPOSE: The study aims to test a
      theoretically based, multi-factorial model for ethnic disparities in children's
      acute asthma visits through parental illness representations. METHODS: Structural
      equation modeling investigated the association of parental asthma illness
      representations, sociodemographic characteristics, health care provider factors,
      and social-environmental context with children's acute asthma visits among 309
      White, Puerto Rican, and African American families was conducted. RESULTS: Forty
      five percent of the variance in illness representations and 30% of the variance
      in acute visits were accounted for. Statistically significant differences in
      illness representations were observed by ethnic group. Approximately 30% of the
      variance in illness representations was explained for whites, 23% for African
      Americans, and 26% for Puerto Ricans. The model accounted for >30% of the
      variance in acute visits for African Americans and Puerto Ricans but only 19% for
      the whites. CONCLUSION: The model provides preliminary support that ethnic
      heterogeneity in asthma illness representations affects children's health
      outcomes.

PMID- 22160800
TI  - Transitions to regular smoking and nicotine dependence in the Adolescent National
      Comorbidity Survey (NCS-A).
AB  - OBJECTIVE: This study aims to investigate the occurrence of nicotine dependence
      following the achievement of previous smoking milestones (initiation, weekly, and
      daily smoking). METHOD: Analyses are based on data from The National Comorbidity
      Survey-Adolescent, a nationally representative face-to-face survey of 10,123
      adolescents (age 13-17) conducted between 2001 and 2004. RESULTS: Among
      adolescents who had ever smoked (36.0%), 40.7% reached weekly smoking levels and
      32.8% had reached daily smoking. Approximately one in five adolescents who had
      ever smoked (19.6%) met criteria for nicotine dependence. An earlier age of
      smoking initiation, a shorter time since the onset of smoking and faster
      transitions among smoking milestones were independently associated with the onset
      of daily smoking and nicotine dependence. CONCLUSIONS: These findings shed new
      light on the course of smoking and nicotine dependence during adolescence by
      demonstrating a rapid transition across smoking stages for those most at risk for
      the development of chronic and dependent use.

PMID- 22160801
TI  - Is a cerebellar deficit the underlying cause of reading disabilities?
AB  - This study investigated whether children with dyslexia differed in their
      performance on reading, phonological, rapid naming, motor, and cerebellar-related
      tasks and automaticity measures compared to reading age (RA)-matched and
      chronological age (CA)-matched control groups. Participants were 51 children
      attending mainstream English elementary schools in Quebec. All participants
      completed measures of IQ, word and nonword reading fluency, elision, nonword
      decoding, rapid naming, bead threading, peg moving, toe tapping, postural
      stability, and muscle tone. Results from both group contrasts and analyses at the
      individual case level did not provide support for claims of motor-cerebellar
      involvement in either typical or atypical reading acquisition. Results were more
      consistent with a phonological core process account of both typical reading and
      reading difficulty. Phonological deficits for children with dyslexia compared to
      RA-matched controls were, however, only evident in group contrasts. Findings thus
      also have important implications for identifying at-risk readers among their same
      aged peers.

PMID- 22160802
TI  - A multicenter phase II study of the stop-and-go modified FOLFOX6 with bevacizumab
      for first-line treatment of patients with metastatic colorectal cancer.
AB  - Currently, no prospective data exists to support a "stop-and-go" modified FOLFOX6
      regimen with bevacizumab in metastatic colorectal cancer (mCRC) patients. This
      study aimed to evaluate the efficacy and safety of this regimen in first-line
      mCRC patients. Eligible patients (age >=20 years) had previously untreated mCRC;
      Eastern Cooperative Oncology Group performance status of 0-2; and adequate
      hematologic, hepatic, and renal function. The modified FOLFOX6 regimen and
      bevacizumab (5 mg/kg) was administered intravenously every 2 weeks. After 8
      cycles, patients received maintenance therapy with simplified LV5FU2 and
      bevacizumab until completion of 8 cycles or disease progression. After
      maintenance therapy, patients received another 8 cycles of modified FOLFOX6 with
      bevacizumab until completion of 8 cycles or disease progression. We recruited 50
      patients between August 2007 and January 2009. The overall response rate was 48%
      (80% confidence interval [CI]; 38.2-58) with outcomes as follows: complete
      response, n = 1; partial response, n = 23; stable disease, n = 21; progression, n
      = 1; and not evaluated, n = 4. Median time to treatment failure was 7.7 months
      (80% CI: 6.2-8.0), and median progression-free survival was 12.8 months (80% CI:
      10.8-14). Grade 3/4 toxicities included neutropenia (40%), nausea (4%), diarrhea
      (14%), thrombosis (4%), and hypertension (4%) et al. Grade 1, 2, or 3 peripheral
      neuropathy was reported in 38%, 40%, and 10% of patients, respectively. The stop
      and-go modified FOLFOX6 and bevacizumab regimen is effective and well tolerated
      as first-line chemotherapy for mCRC patients.

PMID- 22160803
TI  - External Qi of Yan Xin Qigong induces cell death and gene expression alterations
      promoting apoptosis and inhibiting proliferation, migration and glucose
      metabolism in small-cell lung cancer cells.
AB  - Small-cell lung cancer (SCLC) is a highly malignant carcinoma with poor long-term
      survival. Effective treatment remains highly demanded. In the present study, we
      demonstrated that External Qi of Yan Xin Qigong (YXQ-EQ) exerted potent cytotoxic
      effect towards SCLC cell line NCI-H82 via induction of apoptosis. Global gene
      expression profiling identified 39 genes whose expression was altered by YXQ-EQ
      in NCI-82 cells. Among them, semi-quantitative RT-PCR and real-time qPCR analyses
      confirmed that the gene expression levels of apoptotic proteins death-associated
      protein kinase 2 and cell death-inducing DFFA-like effector b were upregulated,
      whereas that of oncoproteins DEK and MYCL1, cell migration-promoting proteins
      CD24 and integrin-alpha 9, and glycolytic enzyme aldolase A were downregulated.
      These findings suggest that YXQ-EQ may exert anticancer effect through modulating
      gene expression in a way that facilitates cancer cell apoptosis while represses
      proliferation, metastasis, and glucose metabolism.

PMID- 22160804
TI  - Ouabain increases iNOS-dependent nitric oxide generation which contributes to the
      hypertrophic effect of the glycoside: possible role of peroxynitrite formation.
AB  - In addition to inotropic effects, cardiac glycosides exert deleterious effects on
      the heart which limit their use for cardiac therapeutics. In this study, we
      determined the possible contribution of ouabain-induced iNOS stimulation to the
      resultant hypertrophic as well as cytotoxic effects of the glycoside on cultured
      adult rat ventricular myocytes. Myocytes were treated with ouabain (50 MUM) for
      up to 24 h. Ouabain significantly increased gene and protein levels of inducible
      nitric oxide synthase (iNOS) which was associated with significantly increased
      release of NO from myocytes as well as increased total release of reactive oxygen
      species (ROS), superoxide anion (O(2) (-)), and increased peroxynitrite formation
      as assessed by protein tyrosine nitration. Administration of ouabain was also
      associated with increased levels of myocyte toxicity as determined by myocyte
      morphology, trypan blue staining and lactate dehydrogenase (LDH) efflux. The
      nonspecific NOS inhibitor Nomega-nitro-L: -arginine methyl ester and the more
      selective iNOS inhibitor 1400W both abrogated the increase in LDH release but had
      no significant effect on either morphology or trypan blue staining. Ouabain also
      significantly increased both myocyte surface area and expression of atrial
      natriuretic peptide indicating a hypertrophic response with both parameters being
      completely prevented by NOS inhibition. The effects of iNOS inhibitors were
      associated with diminished ouabain tyrosine nitration as well as abrogation of
      ouabain-induced p38 and ERK phosphorylation. Our study shows that ouabain is a
      potent inducer of NO formation, iNOS upregulation, and increased production of
      ROS. Inhibition of ouabain-dependent peroxynitrite formation may contribute to
      the antihypertrophic effect of iNOS inhibition possibly by preventing downstream
      MAPK activation.

PMID- 22160805
TI  - Can recovery-oriented mental health services be created in Hong Kong? Struggles
      and strategies.
AB  - Recovery has been adopted as either the national policy or guiding principle for
      reforming mental health services in many countries. Development and
      implementation of the concept of recovery is still in its infancy in most Asian
      countries, and Hong Kong is no exception. The present authors propose three
      strategies to guide the transformation of Hong Kong mental health services toward
      becoming more recovery-oriented.

PMID- 22160806
TI  - Challenges to quality assurance and improvement efforts in behavioral health
      organizations: a qualitative assessment.
AB  - Behavioral health organizations have been increasingly required to implement
      plans to monitor and improve service quality. This qualitative study explores
      challenges that quality assurance and improvement (QA/I) personnel experience in
      performing their job in those practice settings. Sixteen QA/I personnel from
      different agencies in St. Louis, Missouri, U.S.A., were interviewed face-to-face
      using a semi-structured instrument to capture challenges and a questionnaire to
      capture participant and agency characteristics. Data analysis followed a grounded
      theory approach. Challenges involved agency resources, agency buy-in, personnel
      training, competing demands, shifting standards, authority, and research
      capacity. Further research is needed to assess these challenges given expected
      outcomes.

PMID- 22160807
TI  - The perceived rehabilitation needs of people with schizophrenia in Hong Kong:
      perspectives from consumers and care-givers.
AB  - A quantitative survey was conducted to investigate the perceived rehabilitation
      needs based on people with schizophrenia and their caregivers. A total of 194
      persons with schizophrenia and 83 caregivers were recruited by convenience
      sampling to complete the two newly developed questionnaires for this purpose
      which included the Perceived Rehabilitation Needs Questionnaire for People with
      Schizophrenia and the Perceived Rehabilitation Needs Questionnaire for Caregivers
      towards People with Schizophrenia respectively. The findings deepened the
      understanding of this area. Some policy and service development suggestions for
      mental health strategies in Hong Kong and the Asian-Pacific region were made.

PMID- 22160808
TI  - The social meanings of traditional Chinese medicine: elderly Chinese immigrants'
      health practice in the United States.
AB  - We situate elderly Chinese immigrants' utilization of traditional Chinese
      medicine (TCM) in social contexts (e.g., family and social networks), exploring
      how TCM is used as a tool, a resource, and a product of meaning-construction in
      their everyday life. We conducted in in-depth interviews with 20 elderly Chinese
      immigrants in the United State, exploring the complexity of their understanding
      and practice of TCM. We used grounded theory to identify the set of meanings that
      are particular to elderly Chinese immigrants' use of TCM as a part of their
      health practice. For our participants, TCM is not just a resource for illness
      management. Instead, incorporating TCM in their health practice allows them to:
      (a) perform and reaffirm their cultural identity as Chinese, (b) maintain their
      moral status and fulfill their social roles, and (c) pass down health knowledge
      and cultural heritage. Clinical implications were discussed.

PMID- 22160810
TI  - Validation of the BacT/ALERT(r)3D automated culture system for the detection of
      microbial contamination of epithelial cell culture medium.
AB  - Living tissue engineering for regenerative therapy cannot withstand the usual
      pharmacopoeia methods of purification and terminal sterilization. Consequently,
      these products must be manufactured under aseptic conditions at microbiologically
      controlled environment facilities. This study was proposed to validate
      BacT/ALERT((r))3D automated culture system for microbiological control of
      epithelial cell culture medium (ECCM). Suspensions of the nine microorganisms
      recommended by the European Pharmacopoeia (Chap. 2.6.27: "Microbiological control
      of cellular products"), plus one species from oral mucosa and two negative
      controls with no microorganisms were prepared in ECCM. They were inoculated in FA
      (anaerobic) and SN (aerobic) culture bottles (Biomerieux, Lyon, France) and
      incubated in a BacT/ALERT((r))3D automated culture system. For each species, five
      sets of bottles were inoculated for reproducibility testing: one sample was
      incubated at the French Health Products Agency laboratory (reference) and the
      four others at Cell and Tissue Bank of Lyon, France. The specificity of the
      positive culture bottles was verified by Gram staining and then subcultured to
      identify the microorganism grown. The BacT/ALERT((r))3D system detected all the
      inoculated microorganisms in less than 2 days except Propionibacterium acnes
      which was detected in 3 days. In conclusion, this study demonstrates that the
      BacT/ALERT((r))3D system can detect both aerobic and anaerobic bacterial and
      fungal contamination of an epithelial cell culture medium consistent with the
      European Pharmacopoeia chapter 2.6.27 recommendations. It showed the specificity,
      sensitivity, and precision of the BacT/ALERT((r))3D method, since all the
      microorganisms seeded were detected in both sites and the uncontaminated medium
      ECCM remained negative at 7 days.

PMID- 22160811
TI  - GUARDD: user-friendly MATLAB software for rigorous analysis of CPMG RD NMR data.
AB  - Molecular dynamics are essential for life, and nuclear magnetic resonance (NMR)
      spectroscopy has been used extensively to characterize these phenomena since the
      1950s. For the past 15 years, the Carr-Purcell Meiboom-Gill relaxation dispersion
      (CPMG RD) NMR experiment has afforded advanced NMR labs access to kinetic,
      thermodynamic, and structural details of protein and RNA dynamics in the crucial
      MUs-ms time window. However, analysis of RD data is challenging because datasets
      are often large and require many non-linear fitting parameters, thereby
      confounding assessment of accuracy. Moreover, novice CPMG experimentalists face
      an additional barrier because current software options lack an intuitive user
      interface and extensive documentation. Hence, we present the open-source software
      package GUARDD (Graphical User-friendly Analysis of Relaxation Dispersion Data),
      which is designed to organize, automate, and enhance the analytical procedures
      which operate on CPMG RD data ( http://code.google.com/p/guardd/). This MATLAB
      based program includes a graphical user interface, permits global fitting to
      multi-field, multi-temperature, multi-coherence data, and implements chi (2)
      mapping procedures, via grid-search and Monte Carlo methods, to enhance and
      assess fitting accuracy. The presentation features allow users to seamlessly
      traverse the large amount of results, and the RD Simulator feature can help
      design future experiments as well as serve as a teaching tool for those
      unfamiliar with RD phenomena. Based on these innovative features, we expect that
      GUARDD will fill a well-defined gap in service of the RD NMR community.

PMID- 22160809
TI  - Immunomodulation at epithelial sites by obesity and metabolic disease.
AB  - Obesity and related type 2 diabetes are increasing at epidemic proportions
      globally. It is now recognized that inflammatory responses mediated within the
      adipose tissue in obesity are central to the development of disease. Once
      initiated, chronic inflammation associated with obesity leads to the modulation
      of immune cell function. This review will focus specifically on the impact of
      obesity on gammadelta T cells, a T-cell subset that is found in high
      concentrations in epithelial tissues such as the skin, intestine, and lung.
      Epithelial gammadelta T cell function is of particular concern in obesity as they
      are the guardians of the epithelial barrier and mediate repair. A breakdown in
      their function, and subsequently the deterioration of the epithelium can result
      in dire consequences for the host. Obese patients are more prone to non-healing
      injuries, infection, and disease. The resulting inflammation from these
      pathologies further perpetuates the disease condition already present in obese
      hosts. Here we will provide insight into the immunomodulation of gammadelta T
      cells that occurs in the epithelial barrier during obesity and discuss current
      therapeutic options.

PMID- 22160812
TI  - Introducing survival ethics into engineering education and practice.
AB  - Given the possibilities of synthetic biology, weapons of mass destruction and
      global climate change, humans may achieve the capacity globally to alter life.
      This crisis calls for an ethics that furnishes effective motives to take global
      action necessary for survival. We propose a research program for understanding
      why ethical principles change across time and culture. We also propose
      provisional motives and methods for reaching global consensus on engineering
      field ethics. Current interdisciplinary research in ethics, psychology,
      neuroscience and evolutionary theory grounds these proposals. Experimental
      ethics, the application of scientific principles to ethical studies, provides a
      model for developing policies to advance solutions. A growing literature proposes
      evolutionary explanations for moral development. Connecting these approaches
      necessitates an experimental or scientific ethics that deliberately examines
      theories of morality for reliability. To illustrate how such an approach works,
      we cover three areas. The first section analyzes cross-cultural ethical systems
      in light of evolutionary theory. While such research is in its early stages, its
      assumptions entail consequences for engineering education. The second section
      discusses Howard University and University of Puerto Rico/Mayaguez (UPRM) courses
      that bring ethicists together with scientists and engineers to unite ethical
      theory and practice. We include a syllabus for engineering and STEM (Science,
      Technology, Engineering and Mathematics) ethics courses and a checklist model for
      translating educational theory and practice into community action. The model is
      based on aviation, medicine and engineering practice. The third and concluding
      section illustrates Howard University and UPRM efforts to translate engineering
      educational theory into community action. Multidisciplinary teams of engineering
      students and instructors take their expertise from the classroom to global
      communities to examine further the ethicality of prospective technologies and the
      decision-making processes that lead to them.

PMID- 22160813
TI  - Detecting a secreted gastric cancer biomarker molecule by targeted nanoparticles
      for real-time diagnostics.
AB  - PURPOSE: A real time detection of gastric cancer-associated biomarker molecules
      in the lumen of the stomach could assist in early detection of this multi-step
      malignancy. METHODS: Employing alpha1-antitrypsin precursor (A1AT) as a secreted
      biomarker model, a platform with immunoassay capabilities, comprising sensing and
      detecting compartments was developed. It was made of a microarray-type
      functionalized glass, containing a high density of amine groups. Trypsin, the
      capturing moiety, was immobilized to the glass surface with the aid of a PEG
      based spacer mixture, identified as being crucial for both capturing and
      detecting properties. The detecting compartment contained near infrared
      fluorescently labeled nanoparticles conjugated to A1AT-specific antibodies, aimed
      at generating an optical signal, detectable by a conventional endoscope or a
      video capsule. RESULTS: The specific recognition reaction between the captured
      A1AT and the immuno-nanoparticles generated a profound fluorescence with a signal
      to noise ratio (SNR) of 12-32, in a biomarker-concentration dependent manner.
      Moreover, the optical recognition signal was intense enough to be detected by a
      video capsule simulator (with optical detection capabilities of a video capsule)
      with a SNR of 6-20. CONCLUSIONS: This platform could serve as a real time
      diagnostic kit for early detection of a secreted biomarker of gastric cancer.

PMID- 22160814
TI  - Early changes in clinical characteristics after emergency department therapy for
      acute heart failure syndromes: identifying patients who do not respond to
      standard therapy.
AB  - Clinical trials for acute heart failure syndromes (AHFS) have traditionally
      enrolled patients well after emergency department (ED) presentation. We
      hypothesized a large proportion of patients would undergo changes in clinical
      profiles during the first 24 h of hospitalization, and these changes would be
      associated with adverse events. We evaluated a prospective cohort of patients
      with clinical data available at ED presentation and 12-24 h after ED treatment
      for AHFS. Patients were categorized into distinct clinical profiles at these time
      points based on (1) systolic blood pressure: a-hypertensive (>160 mmHg); b
      normotensive (100-159 mmHg); or c-hypotensive (<100 mmHg); (2) moderate-to-severe
      renal dysfunction (GFR <= 60 ml/min/1.73 m(2)); and (3) presence of troponin
      positivity. A composite outcome of 30-day cardiovascular events was determined by
      phone follow-up. In the 370 patients still hospitalized with data available at
      the 12-24 h time point, 196 (53.0%) had changed their clinical profiles, with 117
      (59.7%) improving and 79 (40.3%) worsening. The composite 30-day event rate was
      16.9%. Patients whose clinical profile started and stayed abnormal had a
      significantly greater proportion of events than those who started and stayed
      normal (26.1% vs. 11.3%; P = 0.03). Patients with abnormal clinical profiles at
      presentation that remain abnormal throughout the first 12-24 h of hospitalization
      are at increased risk of 30-day adverse events. Future clinical trials may need
      to consider targeting these patients, as they may be the most likely to benefit
      from experimental therapy.

PMID- 22160815
TI  - The Massachusetts journey to expand health insurance coverage.

PMID- 22160816
TI  - A follow-up report card on computer-assisted diagnosis--the grade: C+.

PMID- 22160817
TI  - Do physician organizations located in lower socioeconomic status areas score
      lower on pay-for-performance measures?
AB  - BACKGROUND: Physician organizations (POs)--independent practice associations and
      medical groups--located in lower socioeconomic status (SES) areas may score
      poorly in pay-for-performance (P4P) programs. OBJECTIVE: To examine the
      association between PO location and P4P performance. DESIGN: Cross-sectional
      study; Integrated Healthcare Association's (IHA's) P4P Program, the largest non
      governmental, multi-payer program for POs in the U.S. PARTICIPANTS: 160 POs
      participating in 2009. MAIN MEASURES: We measured PO SES using established
      methods that involved geo-coding 11,718 practice sites within 160 POs to their
      respective census tracts and weighting tract-specific SES according to the number
      of primary care physicians at each site. P4P performance was defined by IHA's
      program and was a composite mainly representing clinical quality, but also
      including measures of patient experience, information technology and registry
      use. KEY RESULTS: The area-based PO SES measure ranged from -11 to +11 (mean 0,
      SD 5), and the IHA P4P performance score ranged from 23 to 86 (mean 69, SD 15).
      In bivariate analysis, there was a significant positive relationship between PO
      SES and P4P performance (p < 0.001). In multivariate analysis, a one standard
      deviation increase in PO SES was associated with a 44% increase (relative risk
      1.44, 95%CI, 1.22-1.71) in the likelihood of a PO being ranked in the top two
      quintiles of performance (p < 0.001). CONCLUSIONS: Physician organizations'
      performance scores in a major P4P program vary by the SES of the areas in which
      their practice sites are located. P4P programs that do not account for this are
      likely to pay higher bonuses to POs in higher SES areas, thus increasing the
      resource gap between these POs and POs in lower SES areas, which may increase
      disparities in the care they provide.

PMID- 22160818
TI  - Health sources of cancer screening knowledge for Vietnamese women.
AB  - The study examined sources of health information among Vietnamese women and
      whether these sources were associated with cancer screening outcomes. One hundred
      eleven participants completed a questionnaire with measures of breast and
      cervical cancer screening attitudes, efficacy, and behavior. A factor analysis of
      items that measured sources for information on cancer screening produced three
      factors: English media sources, Vietnamese media sources, and informal sources.
      These sources were included along with demographic variables in regression
      analyses to predict cancer screening outcomes. Results indicated that using
      informal sources for breast screening information predicted positive attitudes
      toward breast cancer screening and efficacy for breast and cervical cancer
      screening. Reliance on Vietnamese media sources was associated with lower
      cervical screening efficacy. Being older, having health insurance, and a higher
      income were associated with favorable cancer screening outcomes. The findings
      suggest that cancer screening programs for Vietnamese women should take into
      consideration preferred mediums for receiving health information.

PMID- 22160819
TI  - Substitution and pooling in crowding.
AB  - Unless we fixate directly on it, it is hard to see an object among other objects.
      This breakdown in object recognition, called crowding, severely limits peripheral
      vision. The effect is more severe when objects are more similar. When observers
      mistake the identity of a target among flanker objects, they often report a
      flanker. Many have taken these flanker reports as evidence of internal
      substitution of the target by a flanker. Here, we ask observers to identify a
      target letter presented in between one similar and one dissimilar flanker letter.
      Simple substitution takes in only one letter, which is often the target but, by
      unwitting mistake, is sometimes a flanker. The opposite of substitution is
      pooling, which takes in more than one letter. Having taken only one letter, the
      substitution process knows only its identity, not its similarity to the target.
      Thus, it must report similar and dissimilar flankers equally often. Contrary to
      this prediction, the similar flanker is reported much more often than the
      dissimilar flanker, showing that rampant flanker substitution cannot account for
      most flanker reports. Mixture modeling shows that simple substitution can account
      for, at most, about half the trials. Pooling and nonpooling (simple substitution)
      together include all possible models of crowding. When observers are asked to
      identify a crowded object, at least half of their reports are pooled, based on a
      combination of information from target and flankers, rather than being based on a
      single letter.

PMID- 22160820
TI  - The multiple-weighting-systems hypothesis: theory and empirical support.
AB  - Observers respond faster when the task-relevant perceptual dimension repeats
      across consecutive trials (e.g., color-color) relative to when it changes
      (orientation-color)-the phenomenon termed the dimension repetition effect (DRE).
      Similarly, when two (or more) different tasks are made to vary randomly across
      trials, observers are faster when the task repeats, relative to task changes-the
      phenomenon termed task-switch cost (TSC). Hitherto, the DRE and TSC effects have
      been discussed independently of each other. Critically, either effect was
      explained by assuming a single mechanism giving rise to DREs or TSCs. Here, we
      elaborate strong conceptual similarities between the DRE and TSC effects; we
      introduce the concept of criterion-specific intertrial sequence effects, with
      DREs and TSCs being different manifestations of criterion-specific effects.
      Second, we review available evidence suggesting that none of the single mechanism
      explanations can readily account for all the findings in the literature. Third,
      we elaborate on the multiple-weighting-systems (or MWS) hypothesis, a recently
      proposed account that postulates the existence of several, independent mechanisms
      sensitive to intertrial sequences. Finally, we test predictions derived from the
      MWS hypothesis in two novel experiments and discuss the results from both the
      single- and multiple-mechanism perspectives.

PMID- 22160821
TI  - Improved top-down control reduces oculomotor capture: the case of action video
      game players.
AB  - Action video game players (AVGPs) have been demonstrated to outperform non-video
      game players(NVGPs) on a range of cognitive tasks. Evidence to date suggests that
      AVGPs' enhanced performance in attention based tasks can be accounted for by
      improved top-down control over the allocation of visuospatial attention. Thus,we
      propose that AVGPs provide a population that can be used to investigate the role
      of top-down factors in key models of attention. Previous work using AVGPs has
      indicated that they experience less interfering effects from a salient but task
      irrelevant distractor in an attentional capture paradigm (Chisholm, Hickey,
      Theeuwes, & Kingstone,2010). Two fundamentally different bottom-up and top-down
      models of attention can account for this result. In the present study, we
      compared AVGP and NVGP performance in an oculomotor capture paradigm to address
      when and how top-down control modulates capture. In tracking eye movements, we
      acquired an explicit measurement of attention allocation and replicated the
      covert attention effect that AVGPs are quicker than NVGPs to attend to a target
      in the presence of a task-irrelevant distractor. Critically, our study reveals
      that this top-down gain is the result of fewer shifts of attention to the salient
      distractor, rather than faster disengagement after bottom-up capture has
      occurred. This supports the theory that top-down control can modulate the
      involuntary capture of attention [added].

PMID- 22160822
TI  - Intrinsically photosensitive retinal ganglion cells.
AB  - Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond to light in
      the absence of all rod and cone photoreceptor input. The existence of these
      ganglion cell photoreceptors, although predicted from observations scattered over
      many decades, was not established until it was shown that a novel photopigment,
      melanopsin, was expressed in retinal ganglion cells of rodents and primates.
      Phototransduction in mammalian ipRGCs more closely resembles that of invertebrate
      than vertebrate photoreceptors and appears to be mediated by transient receptor
      potential channels. In the retina, ipRGCs provide excitatory drive to
      dopaminergic amacrine cells and ipRGCs are coupled to GABAergic amacrine cells
      via gap junctions. Several subtypes of ipRGC have been identified in rodents
      based on their morphology, physiology and expression of molecular markers. ipRGCs
      convey irradiance information centrally via the optic nerve to influence several
      functions including photoentrainment of the biological clock located in the
      hypothalamus, the pupillary light reflex, sleep and perhaps some aspects of
      vision. In addition, ipRGCs may also contribute irradiance signals that interface
      directly with the autonomic nervous system to regulate rhythmic gene activity in
      major organs of the body. Here we review the early work that provided the
      motivation for searching for a new mammalian photoreceptor, the ground-breaking
      discoveries, current progress that continues to reveal the unusual properties of
      these neuron photoreceptors, and directions for future investigation.

PMID- 22160823
TI  - Culture-based detection of methicillin-resistant Staphylococcus aureus by a
      network of European laboratories: an external quality assessment study.
AB  - Twenty-three hospital laboratories from Europe and Israel participated in an
      external quality assessment (EQA) of the culture-based detection of methicillin
      resistant Staphylococcus aureus (MRSA). Participants also reported the MRSA
      prevalence in clinical cultures and patient screening specimens, as well as the
      MRSA screening practices employed at their hospitals. An EQA panel of 18 samples
      consisting of two MRSA harbouring SCCmec IV and I, and one strain each of
      methicillin-resistant coagulase-negative S. epidermidis, methicillin-sensitive S.
      aureus and Escherichia coli as pure strains or in mixtures at 10(7)-1 cfu
      absolute loads was analysed by the 23 participants. Seventeen (74%) participants
      identified 17 or more samples correctly. Of these, 15 (88%) utilised a
      chromogenic medium alone (ChromID, bioMerieux; BBL CHROMagar, BD Diagnostics;
      MRSA Select, Bio-Rad Laboratories) or combined with a conventional medium and up
      to three confirmatory tests. Proportions of MRSA among S. aureus isolated from
      clinical cultures varied widely, even among hospitals within countries, ranging
      from 11-20% to 61-70%. MRSA carriage rates were less variable (0-20%) between
      countries. Almost all participants (n=22, 96%) screened patients for MRSA
      carriage during 2009-2010, of which 15 (68%) screened intensive care unit (ICU)
      patients alone or combined with other targeted high-risk groups, and 10 (45%)
      combined nasal screening with another body site.

PMID- 22160824
TI  - Prevalence and distribution of Helicobacter pylori cagA and vacA genotypes in the
      Moroccan population with gastric disease.
AB  - Helicobacter pylori infection is the etiologic agent of various gastric
      pathologies. The severity of disease outcome has been attributed to some H.
      pylori genotypes, which varies geographically. In Morocco, there are no data
      regarding the pattern of H. pylori genotypes; therefore, this is the first
      prospective study conducted in our country to investigate the genotype profiles
      (vacA and cagA) of H. pylori in patients with gastric pain. Endoscopic biopsies
      were obtained in patients attending the gastroenterology department of the
      Hospital University Hassan II of Fez for gastric pain and were directly used for
      H. pylori detection and genotyping by polymerase chain reaction (PCR). The SPSS
      software program was used to study the genotype correlation to different clinical
      outcomes. A total of 429 patients were included in this study, with an infection
      rate of 69.9%. cagA was detected in 42.3% of cases. However, vacA genotyping
      reveal a large predominance of s2m2. Infection with multiple strains was detected
      in 10.8% of cases and incomplete vacA was observed in 31.5%. In Morocco, vacA
      s1m1 was significantly associated to peptic ulcer diseases, while s2m2 was
      associated to gastritis. Moroccan H. pylori vacA genotype profiles differ from
      the Latin American, European, and South African profiles, with more similarities
      to the North African profile. Because of the small number of cases with gastric
      cancer, no correlations with H. pylori have been studied, so, further studies
      will be required in order to highlight the effects of those genes on this
      disease.

PMID- 22160826
TI  - Circulating CXCL11 and CXCL10 are increased in hepatitis C-associated
      cryoglobulinemia in the presence of autoimmune thyroiditis.
AB  - OBJECTIVE: No data are available about circulating levels of the CXCL11 chemokine
      in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) patients with
      or without autoimmune thyroiditis (AT). The aim of the present study, therefore,
      was to evaluate serum CXCL11 levels in these patients. DESIGN: Serum CXCL11 (and
      for comparison, CXCL10) was measured in 45 patients with MC, 45 patients with MC
      and AT (MC + AT), 45 sex- and age-matched controls without AT (control 1), 45 sex
      and age-matched patients with AT without cryoglobulinemia (control 2), and in 45
      sex- and age-matched patients with hepatitis C chronic infection without MC
      (HCV+). RESULTS: Serum CXCL11 and CXCL10 levels were significantly higher in
      control 2 than in control 1 (p < 0.01). MC patients had CXCL11 and CXCL10
      significantly higher than control 1 (p < 0.01). MC + AT patients had CXCL11 and
      CXCL10 higher than control 2 (p < 0.01) and MC patients (p = 0.02). Serum CXCL11
      levels were not associated with any of the clinical features of cryoglobulinemia
      in patients with MC and MC + AT, which was the same for CXCL10. CXCL10 and CXCL11
      in HCV+ patients were significantly higher than in controls 1 and 2, but lower
      than in MC or MC+AT patients. CONCLUSION: Our study first demonstrates higher
      serum levels of CXCL11 chemokine in patients with MC than in HCV+ patients, and
      in particular in the presence of AT.

PMID- 22160825
TI  - Impaired regulatory T cell reconstitution in patients with acute graft-versus
      host disease and cytomegalovirus infection after allogeneic bone marrow
      transplantation.
AB  - To elucidate the correlation between regulatory T cells (Tregs) and acute graft
      versus-host disease (aGVHD) or cytomegalovirus infection following allogeneic
      bone marrow transplantation (allo-BMT), we evaluated either CD4+CD25(high) or
      FOXP3+ Treg-enriched cells in peripheral blood (PB) from 20 patients who received
      allo-BMT, and in biopsies of skin with aGVHD. Proportions of CD4+CD25(high)FOXP3+
      cells in total lymphocytes, but not other types of T cells, were lower in
      patients who eventually developed grades II-IV aGVHD (n = 13) than in others (n =
      7, P < 0.001). Proportions of CD62L+ cells in CD4+CD25(high) cells at day +30
      were lower (P < 0.01) in patients who eventually showed cytomegalovirus viremia
      (n = 6) than in others (n = 14). Incidence of aGVHD (P < 0.05) or cytomegalovirus
      viremia (P < 0.05) was higher in patients without these complications, but with
      lower proportions of PB CD4+CD25(high)FOXP3+ cells at day +30 (n = 8) than in
      others (n = 8). However, in skin with aGVHD (n = 5), there was marked or slightly
      increased infiltration of CD8+ cells (P < 0.001) or CD3+FOXP3+ cells (P < 0.05),
      respectively, when compared with control (n = 5), resulting in threefold higher
      ratio of CD8+/CD3+FOXP3+ cells in aGVHD relative to controls (P < 0.05). Thus,
      impaired reconstitution of Tregs may be associated with aGVHD and CMV infection.
      Moreover, imbalance of Tregs and CD8+ cells may play a role in aGVHD tissue.

PMID- 22160827
TI  - Molecular detection of novel picornaviruses in chickens and turkeys.
AB  - Fecal specimens, including swabs and litter extracts, collected from chickens,
      domestic ducks, turkeys, and Canadian geese were tested using degenerate primers
      targeting regions encoding for conserved amino acid motifs (YGDD and
      DY(T/S)(R/K/G)WDST) in calicivirus RNA-dependent RNA polymerases. Similar motifs
      are also present in other RNA viruses. Two fecal specimens and 18 litter extracts
      collected from chickens and turkeys yielded RT-PCR products. BLAST search and
      phylogenetic analysis revealed that all amplicons represented picornaviruses that
      clustered into two major groups. Four chicken and one turkey samples yielded 250
      bp amplicons with 84-91% nucleotide identity to the recently described turkey
      hepatitis viruses, while 280 and 283 bp amplicons obtained from 11 chicken and 4
      turkey samples represented novel picornaviruses with the closest nucleotide
      identity to kobuviruses (54-61%) and turdiviruses (47-54%). Analysis of 2.2-3.2
      kb extended genome sequences including the partial P2 (2C) and complete P3 (3A,
      3B (VPg), 3C(pro), and 3D(pol)) regions of selected strains indicated that
      viruses yielding the 280/283 bp amplicons represent a putative new genus of
      Picornaviridae. The 3'-non-translated region (NTR) of the turkey hepatitis-like
      viruses described in this study was significantly longer (641-654 nt) than that
      of any of the other piconaviruses and included a putative short open reading
      frame (ORF). In summary, we report the molecular detection of novel
      picornaviruses that appear to be endemic in both chickens and turkeys.

PMID- 22160828
TI  - Birth, death, and replacement of karyopherins in Drosophila.
AB  - Nucleocytoplasmic transport is a broadly conserved process across eukaryotes.
      Despite its essential function and conserved mechanism, components of the nuclear
      transport apparatus have been implicated in genetic conflicts in Drosophila,
      especially in the male germ line. The best understood case is represented by a
      truncated RanGAP gene duplication that is part of the segregation distorter
      system in Drosophila melanogaster. Consistent with the hypothesis that the
      nuclear transport pathway is at the heart of mediating genetic conflicts, both
      nucleoporins and directionality imposing components of nuclear transport have
      previously been shown to evolve under positive selection. Here, we present a
      comprehensive phylogenomic analysis of importins (karyopherins) in Drosophila
      evolution. Importins are adaptor molecules that physically mediate the transport
      of cargo molecules and comprise the third component of the nuclear transport
      apparatus. We find that importins have been repeatedly gained and lost throughout
      various stages of Drosophila evolution, including two intriguing examples of an
      apparently coincident loss and gain of nonorthologous and noncanonical importin
      alpha. Although there are a few signatures of episodic positive selection,
      genetic innovation in importin evolution is more evident in patterns of recurrent
      gene birth and loss specifically for function in Drosophila testes, which is
      consistent with their role in supporting host genomes defense against segregation
      distortion.

PMID- 22160829
TI  - Widdrol activates DNA damage checkpoint through the signaling Chk2-p53-Cdc25A-p21
      MCM4 pathway in HT29 cells.
AB  - Widdrol is an odorant compound isolated from Juniperus chinensis. We previously
      reported that widdrol induces Gap 1 (G1) phase cell cycle arrest and leads to
      apoptosis in human colon adenocarcinoma HT29 cells. It was also reported that
      this cell cycle arrest is associated with the induction of checkpoint kinase 2
      (Chk2), p53 phosphorylation and cyclin dependent kinase (Cdk) inhibitor p21
      expression. In this paper, we investigated the molecular mechanisms of widdrol on
      the activation of G1 DNA damage checkpoint at early phase when DNA damages
      occurred in HT29 cells. First of all, we examined that widdrol breaks DNA
      directly or not. As the results of DNA electrophoresis and formation of
      phosphorylated histone H2AX (gammaH2AX) foci in HT29 cells, widdrol generates DNA
      double-strand breaks directly within 0.5 h both in vitro and in vivo. Based on
      this result, the change of proteins related in checkpoint pathway was examined
      over a time course of 0.5-24 h. Treatment of HT29 cells with widdrol elicits the
      following: (1) phosphorylation of Chk2 and p53, (2) reduction of cell division
      cycle 25A (Cdc25A) expression, (3) increase of Cdk inhibitor p21 expression, and
      (4) decrease of the levels of Cdk2 and cyclin E expression in a time-dependent
      manner. Moreover, only the expression level of mini-chromosome maintenance 4
      (MCM4) protein, a subunit of the eukaryotic DNA replicative helicase, is rapidly
      down-regulated in HT29 cells treated with widdrol over the same time course, but
      those of the other MCM proteins are unchanged. Overall, our results indicated
      that widdrol breaks DNA directly in HT29 cells, and this DNA damage results in
      checkpoint activation via Chk2-p53-Cdc25A-p21-MCM4 pathway and finally cells go
      to G1-phase cell cycle arrest and apoptosis.

PMID- 22160830
TI  - Functional analysis of pig myostatin gene promoter with some adipogenesis- and
      myogenesis-related factors.
AB  - Myostatin (MSTN) is primarily expressed in muscle and plays an important role in
      muscle and fat development in pigs. However, there is little information about
      the regulation of pig MSTN. In order to elucidate whether pig MSTN could be
      regulated by muscle- and fat-related factors, the porcine MSTN promoter was
      amplified and cloned into pGL3-basic vector, and transfected into cells to
      analyze the transcriptional activity of promoter with muscle- and fat-related
      factors through dual-luciferase reporter assays. 5'-deletion expression showed
      that there was a negative-regulatory region located between nucleotides -1519 and
      -1236 bp, and there were some positive-regulatory regions located between -1236
      and -568 bp. The longest fragment (1.7 kb) was cotransfected with muscle-related
      transcription factor myogenic differentiation 1 (MyoD), resulting in promoter
      transcriptional activity upregulation. The fragment was treated by the adipogenic
      agents (DIM) including dexamethasone, insulin, and isobutyl-1-methylxanthine
      (IBMX). We found that MSTN promoter transcriptional activity can be regulated by
      IBMX, but not by DIM. CCAAT/enhancer binding protein (C/EBP) alpha and C/EBPbeta,
      two proteins which are induced by DIM during adipogenesis were cotransfected with
      the 1.7-kb fragment, respectively, resulting in promoter transcriptional activity
      downregulation. Treating the fragment with rosiglitazone which induce the
      expression of peroxisome proliferator-activated receptor gamma (PPARgamma),
      resulting in promoter transcriptional activity upregulation. Cotransfection
      experiments confirmed this result. Taken together, we showed that porcine MSTN
      could be upregulated by IBMX, MyoD, and PPARgamma but downregulated by C/EBPalpha
      and C/EBPbeta.

PMID- 22160831
TI  - Eosinophilic disorders in various diseases.
AB  - Peripheral and tissue eosinophilia are usually associated with a variety of
      inflammatory, malignant, and infectious conditions. As the presence of
      eosinophils in the tissues may cause significant cellular damage to vital organs
      such as the heart, tissue eosinophilia should be diagnosed and treated promptly.
      One operative way to evaluate eosinophilic disorders is to classify them into
      extrinsic and intrinsic. While extrinsic eosinophilic disorders are usually due
      to the production of eosinopoietic factors derived from T cells or tumor cells,
      the intrinsic types generally are the result of genetic mutations in the
      eosinophilic lineage. As we understand more the biology of eosinophils, only a
      few eosinophilic disorders remain idiopathic. The purpose of this article is to
      help the clinician classify in an operational manner most eosinophilic disorders,
      using the extrinsic and intrinsic model. This may facilitate not only a better
      understanding of the role of eosinophils in these disorders, but also help the
      systematic clinical work-up and potential treatment of affected patients.

PMID- 22160832
TI  - First report of human biting activity of Ixodes acutitarsus (Acari: Ixodidae)
      collected in Taiwan.
AB  - Ixodes acutitarsus is said to be the largest Ixodes tick in the world. Human
      biting activity of I. acutitarsus was reported for the first time in Taiwan.
      Ticks were observed from April to December and collected from infested humans
      during trips to the mountainous areas of northern, central, southern and eastern
      Taiwan. Host range, seasonal prevalence, and the vectorial capacity of I.
      acutitarsus ticks for various human pathogens need to be further identified.

PMID- 22160833
TI  - Impact of age, race and decade of treatment on overall survival in a critical
      population analysis of 40,000 multiple myeloma patients.
AB  - With the availability of novel agents, the overall survival (OS) in patients
      diagnosed with multiple myeloma (MM) has improved over the last decade. Data on
      40,294 MM patients in the years from 1973 to 2003 were obtained from the
      Surveillance, Epidemiology, and End Results Program (SEER) of the US National
      Cancer Institute. Statistical analyses evaluating gender, race, age, and year of
      diagnosis were performed using univariate and multivariate Cox regression models
      for the OS endpoint. The mean patient age at diagnosis was 68.3 years. Mean
      survival was 30 months (median = 19 months). Asian/Pacific Islander race was
      associated with an improved OS, HR 0.90 (CI 0.86-0.95, P < 0.001). American
      Indian/Alaska Native race was associated with a decreased OS, HR 1.18 (CI 1.01
      1.38, P = 0.040). Multivariate analysis did not reveal statistically significant
      differences in OS between patients in the white and black race (P = 0.709).
      Younger age (age <65, and 65-75) was associated with improved OS when compared
      with patients >75 years of age (all P < 0.001). Recent treatment decades (1983
      1992 and 1993-2003) were associated with improved OS on multivariate analysis
      with HR 0.88 (CI 0.88-0.89, P < 0.001) and HR 0.83 (CI 0.81-0.85, P < 0.001),
      respectively. As the largest population analysis to date, this study reveals a
      statistically significant improvement in OS for patients who were treated in more
      recent decades, even before the availability of novel agents. Patients who were
      <65 years of age and Asian/Pacific Islander race groups exhibited superior levels
      of OS, whereas American Indian/Alaska Native groups had decreased OS.

PMID- 22160834
TI  - Recombinant activated factor VII (rFVIIa/NovoSeven(r)) in the management of
      severe postpartum haemorrhage: initial report of a multicentre case series in
      Japan.
AB  - Only a limited number of case reports documenting the off-label use of
      recombinant factor VIIa (rFVIIa) in Japanese patients with postpartum haemorrhage
      (PPH) have been published. Data on Japanese cases with severe PPH in which rFVIIa
      was administered were collected. Data of obstetric haemorrhage patients treated
      with rFVIIa between 2005 and 2010 were retrospectively collected throughout
      Japan. The data included patients' background information, blood product
      requirements, dose/timing of rFVIIa, and adverse effects. Treating clinicians
      subjectively assessed the effect of rFVIIa on bleeding at each administration
      using four categories: "Stopped", "Decreased", "Unchanged", and "Increased". A
      total of 25 women received rFVIIa for the treatment of obstetric haemorrhage in
      18 institutions. After the final administration, bleeding was "stopped" in 16
      patients (64%), "decreased" in eight patients (32%), and "unchanged" in one
      patient (4%). A significant reduction in blood product requirement was observed
      following the first rFVIIa administration. Hysterectomy was required in two
      patients (15.4%) after rFVIIa administration. Four asymptomatic thrombotic events
      were reported in three patients. These results suggest that rFVIIa can be a
      beneficial therapeutic option that can reduce blood loss and prevent hysterectomy
      in Japanese patients with massive obstetric bleeding.

PMID- 22160835
TI  - The role of body mass index and other body composition parameters in early post
      transplant complications in patients undergoing allogeneic stem cell
      transplantation with busulfan-cyclophosphamide conditioning.
AB  - Patients with impaired nutritional status may show increased risk of
      hematopoietic stem cell transplantation (HSCT)-related complications. This study
      was conducted to determine whether body mass index (BMI) and other body
      composition parameters, such as lean body mass index (LBMI) and body fat mass
      (BFM), are associated with early post-transplantation toxicity and mortality in
      allogeneic HSCT recipients. The records of 71 patients diagnosed with acute
      myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid
      leukemia (CML), or myelodysplastic leukemia (MDS) who had undergone allogeneic
      HSCT with a conditioning regimen of busulfan-cyclophosphamide (Bu-Cy), between
      September 2003 and January 2009 at the Stem Cell Transplantation Unit of Gazi
      University Hospital were retrospectively evaluated. BMI was found to be
      negatively correlated with the NCI grade of mucositis, cardiotoxicity, emesis,
      and hyperglycemia, and with the number of erythrocyte transfusions. LBMI was also
      negatively correlated with the number of erythrocyte transfusions,
      cardiotoxicity, emesis, and hyperglycemia. BFM was negatively correlated with the
      day of neutrophil engraftment, and NCI grade of mucositis. Nutritional status did
      not have an impact on overall survival (OS), progression-free survival (PFS), or
      100-day transplant related mortality (TRM).

PMID- 22160837
TI  - Immunologic research at Thomas Jefferson University: a recent history.

PMID- 22160836
TI  - Posterior reversible encephalopathy syndrome in an adult patient with acute
      lymphoblastic leukemia after remission induction chemotherapy.
AB  - Posterior reversible encephalopathy syndrome (PRES) has been reported in
      childhood leukemia patients increasingly frequently. However, the development of
      PRES in adult leukemia patients during chemotherapy is very rare. We present a
      case of PRES in an adult patient with acute lymphoblastic leukemia (ALL) after
      remission induction chemotherapy. A 28-year-old woman with ALL was administered
      remission induction chemotherapy consisting of cyclophosphamide, daunorubicin,
      vincristine, prednisone, and L-asparaginase. After initiation of chemotherapy,
      the patient developed paralytic ileus and hypertension, and on day 30, she
      suddenly developed generalized convulsions, loss of visual acuity, and muscle
      weakness in the legs. Magnetic resonance imaging findings and her signs and
      symptoms were typical of PRES. The symptoms gradually improved following
      treatment with an anticonvulsant and an antihypertensive agent, and the patient
      underwent allogeneic bone marrow transplantation. She has completely recovered
      from PRES and has been asymptomatic without leukemia relapse. During remission
      induction chemotherapy for ALL, PRES may be caused by multiple drugs, such as L
      asparaginase, vincristine, and corticosteroids, with different mechanisms of
      action. PRES should be recognized as an important complication, which will occur
      more frequently with the increased intensity of chemotherapy for adult ALL
      patients.

PMID- 22160838
TI  - Youth experiences of family violence and teen dating violence perpetration:
      cognitive and emotional mediators.
AB  - This article describes a conceptual model of cognitive and emotional processes
      proposed to mediate the relation between youth exposure to family violence and
      teen dating violence perpetration. Explicit beliefs about violence, internal
      knowledge structures, and executive functioning are hypothesized as cognitive
      mediators, and their potential influences upon one another are described. Theory
      and research on the role of emotions and emotional processes in the relation
      between youths' exposure to family violence and teen dating violence perpetration
      are also reviewed. We present an integrated model that highlights how emotions
      and emotional processes work in tandem with hypothesized cognitive mediators to
      predict teen dating violence.

PMID- 22160839
TI  - Morphine, but not ketamine, decreases the ratio of Th1/Th2 in CD4-positive cells
      through T-bet and GATA3.
AB  - This study was conducted to investigate the effect of morphine on CD4-positive T
      cells differentiation and the transcriptional factors induced by phorbol
      myristate acetate (PMA) and ionomycin. CD4-positive lymphocytes separated from
      healthy volunteers were incubated by PMA (25 ng/ml) + ionomycin (1 MUg/ml) with
      or without the presence of morphine, ketamine, or naloxone. Th subsets,
      supernatant cytokines, and transcriptional factors were detected 4 h later. Th1
      and Th2 cells, levels of INF-gamma, IL-2, IL-4 and the activities of T-bet and
      GATA3 were significantly increased after incubation with PMA and ionomycin.
      However, the number of Th1 cells, Th1/ Th2, the levels of INF-gamma and INF
      gamma/IL-4, and the activities and protein levels of T-bet and GATA3 were
      decreased after incubation with PMA and ionomycin in the presence of morphine.
      Naloxone can abolish morphine's suppressive effect on Th cell differentiation.
      Morphine has a negative effect on Th cell balance induced by PMA and ionomycin,
      the mechanism is related to T-bet and GATA3.

PMID- 22160840
TI  - The anti-inflammatory mechanism of heme oxygenase-1 induced by hemin in primary
      rat alveolar macrophages.
AB  - Alveolar macrophages (AMs) can initiate lung inflammation by producing pro
      inflammatory cytokines and chemokines, but they participate actively in the
      prevention of inflammation during acute lung injury (ALI). Heme oxygenase-1 (HO
      1) is mainly expressed in AMs and has anti-inflammatory properties in ALI, but
      the anti-inflammatory mechanisms of HO-1 are largely unknown. In this study, AMs
      were treated with saline, LPS (1 MUg/ml), hemin (10 MUM), zinc protoporphyrin
      (ZnPP; 10 MUM, 1 h prior to LPS and hemin), SB203580 (10 MUM, 1 h prior to LPS
      and hemin), or their combination up to 24 h. The specific HO-1 inhibitor ZnPP and
      SB203580 were used to inhibit the effects of HO-1 and the phosphorylated p38
      mitogen-activated protein kinase (MAPK), respectively. The protein levels of HO-1
      and p38 MAPK were analyzed by western blotting; arginase activity was measured in
      lysates obtained from cultured cells; nitric oxide production in the
      extracellular medium of AMs cultured for 24 h was monitored by assessing nitrite
      levels; the phagocytic ability of macrophage was measured by neutral red uptake.
      IL-10 of culture supernatants in AMs was determined by enzyme-linked
      immunosorbent assay. The results indicated that HO-1 induced by hemin increased
      arginase activity and phagocytic ability and decreased iNOS activity via p38 MAPK
      pathway in primary rat AMs. These changes and p38 MAPK may be the anti
      inflammatory mechanism of HO-1 induced by hemin in primary rat AMs.

PMID- 22160841
TI  - Pre-inflammatory mediators and lymphocyte subpopulations in preterm neonates with
      sepsis.
AB  - The aim of this study is to investigate prospectively specific immune system
      factors in preterm neonates with late-onset sepsis and infection-free controls.
      Matched preterm neonates (n = 82) were divided into three groups: suspected
      infection (n = 25), sepsis (n = 17), and infection-free controls (n = 40). Serial
      measurements were made of interleukin-6 (IL-6), IL-1beta, tumor necrosis factor
      alpha (TNF-alpha), lymphocyte subsets [CD3+, CD4+, CD8+, natural killer (NK)
      cells, and B cells], the immunoglobulins (IgG, IgM, and IgA), C-reactive protein
      (CRP), and the total blood count, before, 2 days after initiation of treatment,
      and after stopping treatment. The percentages of NK and B cells were higher in
      the sepsis group, but those of CD3+, CD4+, and CD8+ showed no differences. IgG
      was lower in the sepsis group. IL-6 >30 pg/ml and TNF-alpha >30 pg/ml were
      sensitive sepsis predictors with sensitivity 1 (0.78-1) and 1 (0.79-1),
      respectively, but their specificity was poor. CRP was a specific [0.90 (0.80
      0.96)] but not sensitive index [0.68 (0.48-0.85)], and its combination with IL-6
      or TNF-alpha could enhance their diagnostic accuracy. It is concluded that NK and
      B cells may be elevated in late neonatal sepsis. IL-6 or TNF-alpha combined with
      CRP is a good diagnostic marker for late-onset sepsis in preterm neonates.

PMID- 22160842
TI  - The "Latina epidemiologic paradox" revisited: the role of birthplace and
      acculturation in predicting infant low birth weight for Latinas in Los Angeles,
      CA.
AB  - The "Latina epidemiologic paradox" refers to the observation that despite
      socioeconomic disadvantages, Latina mothers in the United States (US) have a
      similar or lower risk for delivering an infant with low birth weight (LBW)
      compared to non-Latina White mothers. An analogous paradox may exist between
      foreign-born (FB) and US-born (USB) Latinas. Our goal was to assess differences
      in LBW in USB Latinas, FB Latinas, and non-Latina Whites in Los Angeles County in
      2003 using birth records and survey data. Using logistic regression, we estimated
      associations between LBW and birthplace/ethnicity in a birth cohort and nested
      survey responder group and between LBW and acculturation in responders to a
      follow-up survey. USB Latinas and FB Latinas had a higher prevalence of LBW
      infants compared to Whites (odds ratio [OR] = 1.34, 95% confidence interval [CI]
      = (1.17, 1.53) and OR = 1.32, 95% CI = (1.18, 1.49), respectively); when we
      adjusted for additional maternal risk factors these point estimates were
      attenuated, and interval estimates were consistent with a modest positive or
      inverse association. Among Latinas only, LBW was more common for high
      acculturated FB and USB Latinas compared to low-acculturated FB Latinas, and
      there was limited evidence that environmental or behavior risk factors had less
      impact in low-acculturated Latinas. In summary, adjusting only for demographics,
      Latinas in our study were more likely to have LBW infants compared to Whites, in
      contrast to the Latina paradox hypothesis. Furthermore, adjusting for
      environmental or behavioral factors attenuated the positive association, but
      there was little evidence that Latinas had a lower prevalence of LBW regardless
      of the variables included in the models. Finally, among Latinas, there was
      limited evidence that associations between known risk factors and LBW were
      modified by acculturation.

PMID- 22160843
TI  - Brain oscillatory activity associated with task switching and feedback
      processing.
AB  - In this study, we sought to dissociate event-related potentials (ERPs) and the
      oscillatory activity associated with signals indicating feedback about
      performance (outcome-based behavioral adjustment) and the signals indicating the
      need to change or maintain a task set (rule-based behavioral adjustment). With
      this purpose in mind, we noninvasively recorded electroencephalographic signals,
      using a modified version of the Wisconsin card sorting task, in which feedback
      processing and task switching could be studied separately. A similar late
      positive component was observed for the switch and correct feedback signals on
      the first trials of a series, but feedback-related negativity was observed only
      for incorrect feedback. Moreover, whereas theta power showed a significant
      increase after a switch cue and after the first positive feedback of a new
      series, a selective frontal beta-gamma increase was observed exclusively in the
      first positive feedback (i.e., after the selection of the new rule). Importantly,
      for the switch cue, beta-alpha activity was suppressed rather than increased.
      This clear dissociation between the cue and feedback stimuli in task switching
      emphasizes the need to accurately study brain oscillatory activity to disentangle
      the role of different cognitive control processes.

PMID- 22160844
TI  - Clinical significance of serum growth differentiation factor-15 levels in
      systemic sclerosis: association with disease severity.
AB  - OBJECTIVE: To determine serum growth differentiation factor-15 (GDF-15) levels
      and their clinical associations in patients with systemic sclerosis (SSc).
      METHODS: Serum GDF-15 levels were examined by enzyme-linked immunosorbent assay
      in 61 patients with SSc and 24 healthy individuals. In a retrospective
      longitudinal study, sera from 14 patients with SSc were analyzed (duration of
      follow-up 1.2-7.2 years). RESULTS: Serum GDF-15 levels were significantly
      elevated in SSc patients (1340 +/- 910 pg/ml) compared with healthy individuals
      (213 +/- 79 pg/ml; P < 0.001). Among SSc patients, patients with diffuse
      cutaneous SSc (n = 31) had higher levels of serum GDF-15 (1609 +/- 1069 pg/ml)
      than those with limited cutaneous SSc (n = 30; 1142 +/- 646 pg/ml; P < 0.05). SSc
      patients with high GDF-15 levels (>=1000 pg/ml) had pulmonary fibrosis, decreased
      vital capacity, and decreased diffusion capacity for carbon monoxide more often
      than those with low GDF-15 levels (<1000 pg/ml). GDF-15 levels correlated
      positively with the extent of skin sclerosis and inversely with percentage vital
      capacity and diffusion capacity for carbon monoxide in patients with SSc. In a
      longitudinal study, serum GDF-15 levels were generally decreased during the
      follow-up. CONCLUSION: Serum GDF-15 levels were increased in patients with SSc
      and associated with the extent of skin sclerosis and the severity of pulmonary
      fibrosis. These results suggest that GDF-15 may play a role in the development of
      cutaneous and pulmonary fibrosis in SSc. Measurement of serum GDF-15 may be
      useful for risk stratification in early disease stage.

PMID- 22160845
TI  - Therapeutic response of patients with adult Still's disease to biologic agents:
      multicenter results in Japan.
AB  - OBJECTIVE: The efficacy of biologics in treating adult Still's disease (ASD) is
      suggested, but the information is still lacking and the validation is
      insufficient. To determine the efficacy of several biologic agents in refractory
      ASD in Japan, a multicenter survey was performed. METHOD: Clinical data on 16 ASD
      patients who had been treated with at least 1 of the biological agents (total 24
      occasions) were collected retrospectively. RESULTS: Infliximab was used in 9
      cases, etanercept in 4, and tocilizumab in 11. Half of the patients that had been
      treated initially with infliximab or etanercept were changed to another
      biologics. Tocilizumab was effective in cases switched from another 2 drugs.
      Tocilizumab showed efficacy in treating both systemic and arthritic symptoms and
      showed apparent steroid-sparing effect and the highest continuation rate.
      CONCLUSION: Tocilizumab may be a promising biologic agent in refractory ASD.

PMID- 22160846
TI  - In vitro activity and in vivo efficacy of tigecycline alone and in combination
      with daptomycin and rifampin against Gram-positive cocci isolated from surgical
      wound infection.
AB  - The aim of this work was to determine the in vitro activity of tigecycline and
      its bactericidal effect for a large number of Gram-positive cocci, as well as to
      investigate its in vitro interaction with six clinically used antibiotics. In
      vivo, a wound model was established through the panniculus carnosus of BALB/c
      mice, and then inoculated with 5 * 10(7) colony-forming units (CFU) of
      Staphylococcus aureus or Enterococcus faecalis. For each bacterial strain, the
      study included an infected or non-infected group that did not receive any
      treatment, three groups singly treated with tigecycline, rifampin, and
      daptomycin, and two groups that received tigecycline treatment plus rifampin or
      daptomycin. In the in vitro studies, tigecycline, daptomycin, and teicoplanin
      were active against all of the 48 Gram-positive isolates. The combination of
      tigecycline with rifampicin and daptomycin was synergistic against S. aureus and
      Enterococcus spp. In the in vivo studies, all groups treated with single drugs
      showed statistically significant results compared to the control group. The two
      groups treated with a combination of drugs showed the highest antimicrobial
      efficacy. In conclusion, our results suggested a strong activity of tigecycline
      alone and in combination with other antimicrobial agents against multi-resistant
      Gram-positive organisms isolated from wound infections.

PMID- 22160847
TI  - Blood pressure monitoring technique impacts hypertension treatment.
AB  - BACKGROUND: In 2005 the American Heart Association (AHA) released updated
      recommendations for blood pressure (BP) monitoring in order to ensure accurate BP
      measurements. OBJECTIVE: To determine if current methods of BP assessment in an
      ambulatory clinic result in significantly different BP measurements than those
      obtained by following the AHA recommendations and if these BP differences impact
      treatment decisions. RESEARCH DESIGN: Randomized prospective analysis. SETTING:
      University of New Mexico Hospital Adult Internal Medicine clinic. PATIENTS: Forty
      adults with hypertension METHODS: Patient BPs were measured using both the
      traditional triage method and the AHA-recommended method in cross-over fashion in
      random order. Two complete medical profile summaries were then constructed for
      each patient: one for each BP measurement obtained by each technique. These
      profiles were then reviewed by a panel of providers who provided hypothetical
      hypertension treatment recommendations. RESULTS: Individual BP results varied
      greatly between the two methods. SBP readings differed by >=5 mmHg in either
      direction for 68% of patients while 78% of patient's DBP readings differed by >=2
      mmHg in either direction. Overall, 93% of patients had a BP difference of either
      >=5 mmHg systolic or >=2 mmHg diastolic. Five patients were determined to be at
      goal with the triage method, but were higher than their goal BP with the AHA
      method Significant differences were also seen in treatment recommendations for a
      given patient based on the differences seen between the two obtained BP readings.
      The number of patients with treatment variations between their two profiles
      ranged from 13% to 23% depending on the reviewing provider (p < 0.01 for all
      providers). CONCLUSION: Inaccurate BP assessment is common and may impact
      hypertension treatment decisions.

PMID- 22160848
TI  - P2X3 receptor expression by HEK cells conditions their survival.
AB  - On nociceptive neurons, one important mechanism to generate pain signals is the
      activation of P2X3 receptors, which are membrane proteins gated by extracellular
      ATP. In this work, we have studied the recovery of recombinant P2X3 receptor
      expression in human embryonic kidney (HEK) cells. Our data demonstrated that HEK
      cells were not permissive for stable P2X3 expression, since the significant time
      dependent cell loss. In vivo treatment with P2X3 receptor antagonist limited the
      effect. The expression of a single P2X3 point mutant Y393A, also largely
      accelerated cell death. We suggest the requirements of a permissive intracellular
      molecular machinery for appropriate receptor expression. The present report
      suggests that despite HEK cells are often used as recombinant expression system
      for the study a variety of receptors function, they represent a limiting
      permissive environment for P2X3 receptors.

PMID- 22160849
TI  - Introduction to the minireviews series on mitochondrial matters in amyotrophic
      lateral sclerosis, Lou Gehrig's disease.

PMID- 22160850
TI  - Mitochondria from Dipodascus (Endomyces) magnusii and Yarrowia lipolytica yeasts
      did not undergo a Ca2+-dependent permeability transition even under anaerobic
      conditions.
AB  - In this study we used tightly-coupled mitochondria from Yarrowia lipolytica and
      Dipodascus (Endomyces) magnusii yeasts. The two yeast strains are good
      alternatives to Saccharomyces cerevisiae, being aerobes containing well
      structured mitochondria (thus ensuring less structural limitation to observe
      their appreciable swelling) and fully competent respiratory chain with three
      invariantly functioning energy conservation points, including Complex I, that can
      be involved in induction of the canonical Ca2+/P(i)-dependent mitochondrial
      permeability transition (mPTP pore) with an increased open probability when
      electron flux increases(Fontaine et al. J Biol Chem 273: 25734-25740, 1998;
      Bernardi et al. FEBS J 273:2077-2099, 2006). High amplitude swelling and collapse
      of the membrane potential were used as parameters for demonstrating pore opening.
      Previously (Kovaleva et al. J Bioenerg Biomembr 41:239-249, 2009; Kovaleva et al.
      Biochemistry (Moscow) 75: 297-303, 2010) we have shown that mitochondria from
      Y.lipolytica and D. magnusii were very resistant to the Ca2+overload combined
      with varying concentrations of P(i),palmitic acid, SH-reagents,
      carboxyatractyloside (an inhibitor of ADP/ATP translocator), as well as depletion
      of intramitochondrial adenine nucleotide pools, deenergization of mitochondria,
      and shifting to acidic pH values in the presence of high [P(i)]. Here we
      subjected yeast mitochondria to other conditions known to induce an mPTP in
      animal and plant mitochondria, namely to Ca2+ overload under hypoxic conditions
      (anaerobiosis). We were unable to observe Ca2+-induced high permeability of the
      inner membrane of D. magnusii and Y. lipolytica yeast mitochondria under
      anaerobic conditions, thus suggesting that an mPTP-like pore, if it ever occurs
      in yeast mitochondria, is not coupled with the Ca2+ uptake. The results provide
      the first demonstration of ATP-dependent energization of yeast mitochondria under
      conditions of anaerobiosis.

PMID- 22160851
TI  - High knowledge about obesity and its health risks, with the exception of cancer,
      among Mexican individuals.
AB  - Mexico has the second biggest prevalence in the world of obese adults (30%). We
      conducted a survey to determine knowledge concerning obesity co-morbidities.
      Three groups were surveyed with a questionnaire divided into three sections:
      demographic characteristics; knowledge and awareness in relation to obesity being
      a disease; causes of obesity and the health risks it represents; weight auto
      perception and the subject's personal experiences regarding weight. In all groups
      we found high knowledge regarding that obesity is a disease and the causes of its
      development, as well as that it greatly increases the risk of presenting type 2
      diabetes, high blood pressure and knee osteoarthritis. However, in all groups,
      there was a gap in knowledge regarding the risk obesity poses for the development
      of breast and colon cancer. Aggressive health promotion campaigns concerning
      obesity, which have been implemented recently in Mexico, must emphasize cancer as
      a potential outcome for obese patients.

PMID- 22160853
TI  - Phase I study of the safety, tolerability and pharmacokinetics of PHA-848125AC, a
      dual tropomyosin receptor kinase A and cyclin-dependent kinase inhibitor, in
      patients with advanced solid malignancies.
AB  - PURPOSE: This phase I trial assessed the safety, maximally tolerated dose (MTD)
      and pharmacokinetics of TRKA/CDK inhibitor PHA-848125AC in adult patients with
      advanced/metastatic solid tumors. PATIENTS AND METHODS: Patients with relapsed or
      refractory solid tumors, for which no standard therapy existed, were eligible.
      PHA-848125AC was administered orally in two schedules: daily for 7 consecutive
      days in 2-week cycles (i.e. 7 days on/7 days off q2wks; S1) or daily for 4
      consecutive days a week for 3 weeks in 4-week cycles (i.e. 4 days on/3 days off x
      3wks q4wks; S2). RESULTS: Thirty-seven patients were treated in this study, 22 in
      S1 and 15 in S2. The recommended phase II dose (RP2D) was 150 mg/day for either
      schedule. The dose-limiting toxicities (DLTs) in S1 included ataxia (Grade 2-4)
      and tremors (Grade 2-3). In S2, DLTs included tremors (Grade 2-3), elevated
      lipase (Grade 3), increased creatinine (Grade 2), and nausea and vomiting (Grade
      3). These events were all reversible. In S2, out of 14 patients evaluable for
      efficacy, 2 patients with thymic carcinoma, showed partial response and stable
      disease was observed in 3 patients. Stable disease was observed in 6 out 14
      patients evaluable for efficacy on S1. Drug pharmacokinetics demonstrated a half
      life of approximately 33 h, and dose-proportionality with accumulation by a
      factor of 3 after repeated administrations. CONCLUSION: The RP2D of PHA-848125AC
      was 150 mg/day on both schedules. Based on the responses noted in thymic
      carcinoma, a phase II study for patients with that disease is currently
      enrolling.

PMID- 22160854
TI  - A phase I study of temozolomide and everolimus (RAD001) in patients with newly
      diagnosed and progressive glioblastoma either receiving or not receiving enzyme
      inducing anticonvulsants: an NCIC CTG study.
AB  - PURPOSE: This phase I trial was designed to determine the recommended phase II
      dose(s) of everolimus (RAD001) with temozolomide (TMZ) in patients with
      glioblastoma (GBM). Patients receiving enzyme-inducing antiepileptic drugs
      (EIAEDs) and those not receiving EIAEDs (NEIAEDs) were studied separately.
      PATIENTS AND METHODS: Enrollment was restricted to patients with proven GBM,
      either newly diagnosed or at first progression. Temozolomide was administered at
      a starting dose of 150 mg/m(2)/day for 5 days every 28 days, and everolimus was
      administered continuously at a starting dose of 2.5 mg orally on a daily schedule
      starting on day 2 of cycle 1 in 28-day cycles. RESULTS: Thirteen patients
      receiving EIAEDs and 19 not receiving EIAEDs were enrolled and received 83 and
      116 cycles respectively. Everolimus 10 mg daily plus TMZ 150 mg/m(2)/day for 5
      days was declared the recommended phase II dose for the NEIAEDs cohort. In the
      EIAEDs group, doses were well tolerated without DLTs, and pharmacokinetic
      parameters indicated decreased everolimus exposure. Temozolomide pharmacokinetic
      parameters were unaffected by EIAEDs or everolimus. In the subset of 28 patients
      with measurable disease, 3 had partial responses (all NEIAEDs) and 16 had stable
      disease. CONCLUSION: A dosage of 10 mg everolimus daily with TMZ 150 mg/m(2)/day
      for five consecutive days every 28 days in patients is the recommended dose for
      this regimen. Everolimus clearance is increased by EIAEDs, and patients receiving
      EIAEDs should be switched to NEIAEDs before starting this regimen.

PMID- 22160855
TI  - Comparative epigenetic analysis of Oct4 regulatory region in RA-induced
      differentiated NT2 cells under adherent and non-adherent culture conditions.
AB  - Oct4 is a POU domain homeobox gene, expressed in undifferentiated embryonal
      carcinoma and embryonic stem cells and is quickly down-regulated upon induction
      of differentiation. Transcriptional repression of Oct4 is followed by pronounced
      epigenetic changes on the regulatory region of the gene. Oct4 has a long upstream
      regulatory region of about 2,600 bp, consisting of proximal enhancer (PE), distal
      enhancer (DE), and proximal promoter (PP). In this study, we induced
      differentiation of a human embryonic carcinoma cell line, NT2, under two
      different adherent and non-adherent culture conditions, and compared histone
      modifications as the epigenetic marks on the regulatory region of Oct4 gene after
      3 days of differentiation. Using chromatin immunoprecipitation coupled with real
      time PCR technique, it was shown that the after induction of differentiation the
      repressive epigenetic marks of hypoacetylation and methylation on lysine-9 of
      histone H3 occurred very effectively on the upstream of Oct4, especially in PP
      region. Also, comparing the two culturing systems it was shown that methylation
      of lysine-9 of H3 histone was more drastic in PE region of adherent cells rather
      than suspension cells. This epigenetic profile was in agreement with the
      difference observed in the expression level of Oct4 in these two culturing
      systems. The current study clearly shows the effective role of cell culture
      condition on the epigenetic regulation of gene expression.

PMID- 22160856
TI  - Conditioned medium from hypoxic cells protects cardiomyocytes against ischemia.
AB  - The hypothesis of the present study is that cardiomyocytes subjected to prolonged
      ischemia, may release survival factors that will protect new cardiac cells from
      ischemic stress. We exposed neonatal rat cardiomyocyte primary cultures to
      hypoxia, collected the supernatant, treated intact cardiac cells by this
      posthypoxic supernatant, and exposed them to hypoxia. The results show
      cardioprotection of the treated cells compared with the untreated ones. We named
      the collected posthypoxic supernatant "conditioned medium" (CM), which acts in a
      dose-dependent manner to protect new cardiac cells from hypoxia: 100 or 75% of CM
      diluted in phosphate-buffered saline (PBS) protected cells as if they were not
      exposed to hypoxia (P < 0.001). When CM was removed from the cells before
      hypoxia, protection was not observed. CM also protected skeletal muscle cultures
      from hypoxia, but not cardiac cells against H(2)O(2)-induced cell damage.
      Finally, CM treatment protected the isolated heart in Langendorff set-up against
      ischemia. Smaller infarct size (9.9 +/- 4.4% vs. 28.3 +/- 8.5%, P < 0.05), better
      Rate Pressure Product (67 +/- 11% vs. 48.6 +/- 13.4%, P < 0.05) and better rate
      of contraction and relaxation were observed following ischemia and reperfusion
      (1341 +/- 399 mmHg/s vs. 951 +/- 349 mmHg/s, P < 0.05 and 1053 +/- 347 mmHg/s vs.
      736 +/- 314 mmHg/s, P < 0.05). To conclude, there are factors that are released
      from the heart cells subjected to ischemia/hypoxia that protects cardiomyocytes
      from ischemic stress.

PMID- 22160857
TI  - Myocardial infarction in mice alters sarcomeric function via post-translational
      protein modification.
AB  - Myocardial physiology in the aftermath of myocardial infarction (MI) before
      remodeling is an under-explored area of investigation. Here, we describe the
      effects of MI on the cardiac sarcomere with focus on the possible contributions
      of reactive oxygen species. We surgically induced MI in 6-7-month-old female CD1
      mice by ligation of the left anterior descending coronary artery. Data were
      collected 3-4 days after MI or sham (SH) surgery. MI hearts demonstrated
      ventricular dilatation and systolic dysfunction upon echo cardiographic analysis.
      Sub-maximum Ca-activated tension in detergent-extracted fiber bundles from
      papillary muscles increased significantly in the preparations from MI hearts.
      Ca(2+) sensitivity increased after MI, whereas cooperativity of activation
      decreased. To assess myosin enzymatic integrity we measured splitting of Ca-ATP
      in myofibrillar preparations, which demonstrated a decline in Ca-ATPase activity
      of myofilament myosin. Biochemical analysis demonstrated post-translational
      modification of sarcomeric proteins. Phosphorylation of cardiac troponin I and
      myosin light chain 2 was reduced after MI in papillary samples, as measured using
      a phospho-specific stain. Tropomyosin was oxidized after MI, forming disulfide
      products detectable by diagonal non-reducing-reducing SDS-PAGE. Our analysis of
      myocardial protein oxidation post-MI also demonstrated increased S
      glutathionylation. We functionally linked protein oxidation with sarcomere
      function by treating skinned fibers with the sulfhydryl reducing agent
      dithiothreitol, which reduced Ca(2+) sensitivity in MI, but not SH, samples. Our
      data indicate important structural and functional alterations to the cardiac
      sarcomere after MI, and the contribution of protein oxidation to this process.

PMID- 22160858
TI  - Endonuclease G interacts with histone H2B and DNA topoisomerase II alpha during
      apoptosis.
AB  - Apoptosis is a natural form of cell death involved in many physiological changes
      in the cell. Defects in the process of apoptosis can lead to serious diseases.
      During some apoptotic pathways, proteins apoptosis-inducing factor (AIF) and
      endonuclease G (EndoG) are released from the mitochondria and they translocate
      into the cell nuclei, where they probably participate in chromatin degradation
      together with other nuclear proteins. Exact mechanism of EndoG activity in cell
      nucleus is still unknown. Some interacting partners like flap endonuclease 1,
      DNase I, and exonuclease III were already suggested, but also other interacting
      partners were proposed. We conducted a living-cell confocal fluorescence
      microscopy followed by an image analysis of fluorescence resonance energy
      transfer to analyze the possibility of protein interactions of EndoG with histone
      H2B and human DNA topoisomerase II alpha (TOPO2a). Our results show that EndoG
      interacts with both these proteins during apoptotic cell death. Therefore, we can
      conclude that EndoG and TOPO2a may actively participate in apoptotic chromatin
      degradation. The possible existence of a degradation complex consisting of EndoG
      and TOPO2a and possibly other proteins like AIF and cyclophilin A have yet to be
      investigated.

PMID- 22160859
TI  - Selective isolation of dematiaceous fungi from the workers of Atta laevigata
      (Formicidae: Attini).
AB  - Leaf-cutting ants (Formicidae: Attini) are considered pests in agriculture for
      their impact in human crops, as they utilize leaf fragments to raise their fungal
      mutualist (Agaricales: Lepiotaceae). Basically, the basidiomycetous fungus is
      cultivated to supply food to adult workers and broads; in return, the ants
      protect it against natural enemies. However, recent studies have claimed that
      other microorganisms are associated to ant nests where a wide range of
      interactions may take place. To investigate the occurrence of dematiaceous fungi
      on the cuticle of Atta laevigata ants, 30 workers were sampled from an adult nest
      located in the surroundings of the Center for the Studies of Social Insects,
      UNESP-Rio Claro, SP, Brazil. The use of selective techniques to avoid high
      sporulation fungi has been recommended and was tested in this study. To favor the
      isolation of the desired fungi, heads and cuticle scrapings of ant bodies were
      inoculated on Mycosel agar and incubated for 3 weeks at 35 degrees C.
      Morphological and molecular methods were used to identify the filamentous fungi
      recovered. From 56 isolates, 19 were hyaline filamentous species, and among the
      remaining 37, some are mentioned as phyto-associated fungi like Alternaria
      arborescens, Bipolaris sorokiniana, Bipolaris eleusines, Bipolaris zeae,
      Curvularia trifolii, and Paraphaeosphaeria michotii. These species are reported
      from A. laevigata bodies for the first time. None of the isolation trials
      revealed the presence of the parasite Escovopsis or entomopathogenic fungi. The
      possible spread of the fungi in nature by the ants is discussed.

PMID- 22160860
TI  - Caspase-8 isoform 6 promotes death effector filament formation independent of
      microtubules.
AB  - Caspase-8 can trigger cell death following prodomain-mediated recruitment to the
      'death-inducing signaling complex.' The prodomain consists of two death effector
      domain (DED) motifs that undergo homotypic interactions within the cell. Aside
      from mediating recruitment of procaspase-8, the prodomains have also been
      implicated in regulating cell survival, proliferation, death, senescence,
      differentiation, and substrate attachment. Here, we perform the initial
      characterization of a novel isoform of caspase-8, designated caspase-8 isoform 6
      (Casp-8.6), which encodes both prodomain DEDs followed by a unique C-terminal
      tail. Casp-8.6 is detected in cells of the hematopoietic compartment as well as
      several other tissues. When Casp-8.6 expression is reconstituted in caspase-8
      deficient cells, Casp-8.6 does not significantly impact cellular proliferation,
      contrasting with our previous results using a domain-defined 'DED-only' construct
      that lacks the C-terminal tail. Like the DED-only construct, Casp-8.6 also
      robustly forms 'death effector' filaments, but in contrast to the DED construct,
      it does not exhibit a dependence upon intact microtubules to scaffold filament
      formation. Both types of death effector filaments promote apoptosis when
      expressed in the presence of full length caspase-8 (isoform 1). Together, the
      results implicate Casp-8.6 as a new physiological modulator of apoptosis.

PMID- 22160861
TI  - Neuroprotective effects of human mesenchymal stem cells on neural cultures
      exposed to 6-hydroxydopamine: implications for reparative therapy in Parkinson's
      disease.
AB  - Stem cell (SC) transplantation represents a promising tool to treat
      neurodegenerative disorders, such as Parkinson's disease (PD), but positive
      therapeutic outcomes require elucidation of the biological mechanisms involved.
      Therefore, we investigated human Mesenchymal SCs (hMSCs) ability to protect
      murine differentiated Neural SCs (mdNSCs) against the cytotoxic effects of 6
      hydroxydopamine (6-OHDA) in a co-culture model mimicking the in vivo
      neurovascular niche. The internalization of 6-OHDA mainly relies on its uptake by
      the dopamine active transporter (DAT), but its toxicity could also involve other
      pathways. We demonstrated that mdNSCs consistently expressed DAT along the
      differentiative process. Exposure to 6-OHDA did not affect hMSCs, but induced DAT
      independent apoptosis in mdNSCs with generation of reactive oxygen species and
      caspases 3/7 activation. The potential neuroprotective action of hMSCs on mdNSCs
      exposed to 6-OHDA was tested in different co-culture conditions, in which hMSCs
      were added to mdNSCs prior to, simultaneously, or after 6-OHDA treatment. In the
      presence of the neurotoxin, the majority of mdNSCs acquired an apoptotic
      phenotype, while co-cultures with hMSCs significantly increased their survival
      (up to 70%) in all conditions. Multiplex human angiogenic array analysis on the
      conditioned media demonstrated that cytokine release by hMSCs was finely
      modulated. Moreover, sole growth factor addition yielded a similar
      neuroprotective effect on mdNSCs. In conclusion, our findings demonstrate that
      hMSCs protect mdNSCs against 6-OHDA neurotoxicity, and rescue cells from ongoing
      neurodegeneration likely through the release of multiple cytokines. Our findings
      provide novel insights for the development of therapeutic strategies designed to
      counteract the neurodegenerative processes of PD.

PMID- 22160862
TI  - Does aggressive glycemic control benefit macrovascular and microvascular disease
      in type 2 diabetes? Insights from ACCORD, ADVANCE, and VADT.
AB  - Diabetes is increasing rapidly worldwide and frequently results in severe
      vascular complications. A target glycated hemoglobin of less than 7% has commonly
      been recommended in hopes of preventing both macrovascular and microvascular
      complications. Although results from trials of intensive glycemic control have
      generally supported the notion that lower glycated hemoglobin values reduce
      microvascular disease, the evidence for similar benefits for macrovascular
      disease has been less clear. As macrovascular disease is the major cause of
      morbidity and mortality in type 2 diabetes, this remains one of the more
      important unresolved clinical questions. Recent results from the ACCORD, ADVANCE,
      and VADT studies have challenged the conventional believe that lower glycated
      hemoglobin values should be pursued in all diabetic patients. Factors that may
      influence whether intensive glucose management is advisable include duration of
      diabetes, pre-existing macrovascular disease, hypoglycemic unawareness, and
      significant comorbidities. Glycated hemoglobin goals should account for these
      factors and be individualized for each patient.

PMID- 22160863
TI  - Bacopa monnieri extract offsets rotenone-induced cytotoxicity in dopaminergic
      cells and oxidative impairments in mice brain.
AB  - Bacopa monnieri (BM), an ayurvedic medicinal herb is widely known for its memory
      enhancing ability and improvement of brain function. In this study, we tested the
      hypothesis that BM extract (BME) could offset neurotoxicant-induced oxidative
      dysfunctions in developing brain in a rotenone (ROT) mouse model. Pretreatment of
      dopaminergic (N27 cell lines) cells with BME exhibited significant cytoprotective
      effect as evidenced by the attenuation of ROT-induced oxidative stress and cell
      death. Further, the neuroprotective efficacy of BME was assessed in prepubertal
      mice administered ROT (i.p. 1.0 mg/kg b.w./day) for 7 days. BME treatment
      significantly offset ROT-induced oxidative damage in striatum (St) and other
      brain regions as evident by the normalized levels of oxidative markers
      (malondialdehyde, ROS levels, and hydroperoxides) and restoration of depleted GSH
      levels. Further, BME effectively normalized the protein carbonyl content in all
      brain regions suggesting its ability to prevent protein oxidation. Furthermore,
      BME treatment restored the activity levels of cytosolic antioxidant enzymes,
      neurotransmitter function, and dopamine levels in St. Based on our findings, we
      hypothesize that the neuroprotective effects of BM extract may be at least in
      part related to its ability to enhance reduced glutathione and antioxidant
      defenses in brain regions. It is suggested that BM may be effectively exploited
      as a prophylactic/therapeutic adjuvant for neurodegenerative disorders involving
      oxidative stress.

PMID- 22160864
TI  - Subacute seizure incidence in thrombolysis-treated ischemic stroke patients.
AB  - BACKGROUND: To assess the incidence of seizures in acute ischemic stroke patients
      treated with chemical (tPA) thrombolysis. METHODS: Retrospective study including
      all thrombolysis patients treated in Calgary between January 1, 2001, and October
      31, 2006. Descriptive statistics and age/sex-adjusted P values were calculated.
      RESULTS: Of 400 eligible patients (median age 74.0 years, range: 24-77), 16 (4%)
      developed post-stroke seizures: 10 (62.5%) within one week (early) and 6 (37.5%)
      after 1 week but within the hospital stay (late). Single-vessel anterior
      circulation involvement (93.8% vs. 87%, P = 0.34) and hemorrhage (37.5% vs. 20%,
      P = 0.15) were more common in those with compared to without seizures but did not
      reach statistical significance. Atrial fibrillation was more common in those with
      (56.3%) than without (36.1%) seizures (P = 0.04). Death during admission was more
      likely (P = 0.03) in those who sustained seizures (37.5%) compared to those
      without seizures (17.6%). CONCLUSIONS: In this cohort of tPA-treated patients,
      post-stroke seizures were associated with atrial fibrillation and early
      mortality.

PMID- 22160865
TI  - Intraventricular nicardipine for aneurysmal subarachnoid hemorrhage related
      vasospasm: assessment of 90 days outcome.
AB  - BACKGROUND: Delayed cerebral arterial vasospasm is one of the leading causes of
      death and disability after aneurysmal subarachnoid hemorrhage (aSAH). We
      evaluated the safety of intraventricular nicardipine (IVN) for vasospasm (VSP) in
      aSAH patients, and outcomes compared with a control population. METHODS: A
      retrospective case-control study was conducted for aSAH patients treated with IVN
      at Mayo Clinic, Jacksonville, FL, from March 2009 to January 2011. Controls were
      matched by age, gender, and Fisher grade. Safety was evaluated by the incidence
      of intracranial bleeding and infection. Outcome was measured by Glasgow Outcome
      Scale at 30 and 90 days. IVN effects on VSP were evaluated by transcranial
      Doppler (TCD). RESULTS: Thirteen aSAH patients and one arteriovenous malformation
      (AVM)-related SAH patient received IVN for VSP and were matched with 14 aSAH
      patients without IVN therapy for a total of 28 cases. Median dose was 4 mg (range
      3-7), and median number of doses was seven (range 1-17). Mean flow velocity
      decreased after IVN (120.2 and 101.6 cm/s-82.0 and 72.8 cm/s, right and left
      middle cerebral arteries, respectively). No significant difference was seen in
      clinical outcomes between controls and cases at 30 days (P = 0.443) and 90 days
      (P = 0.153). There were no incidences of bleeding or infection with 111
      nicardipine injections. CONCLUSIONS: IVN appears relatively safe and effective in
      treating VSP by TCD, but there was no difference in clinical outcomes between
      nicardipine and control patients at 30 and 90 days. In the future, larger studies
      are needed to evaluate the clinical outcome with IVN.

PMID- 22160867
TI  - Epidermal growth factor receptor downregulation by small heterodimeric binding
      proteins.
AB  - No single engineered protein has been shown previously to robustly downregulate
      epidermal growth factor receptor (EGFR), a validated cancer target. A panel of
      fibronectin-based domains was engineered to bind with picomolar to nanomolar
      affinity to multiple epitopes of EGFR. Monovalent and homo- and hetero-bivalent
      dimers of these domains were tested for EGFR downregulation. Selected
      orientations of non-competitive heterodimers decrease EGFR levels by up to 80% in
      multiple cell types, without activating receptor signaling. These heterodimers
      inhibit autophosphorylation, proliferation and migration, and are synergistic
      with the monoclonal antibody cetuximab in these activities. These small (25 kDa)
      heterodimers represent a novel modality for modulating surface receptor levels.

PMID- 22160868
TI  - Directed evolution of mammalian anti-apoptosis proteins by somatic hypermutation.
AB  - Recently, researchers have created novel fluorescent proteins by harnessing the
      somatic hypermutation ability of B cells. In this study, we examined if this
      approach could be used to evolve a non-fluorescent protein, namely the anti
      apoptosis protein Bcl-x(L), using the Ramos B-cell line. After demonstrating that
      Ramos cells were capable of mutating a heterologous bcl-x(L) transgene, the cells
      were exposed to multiple rounds of the chemical apoptosis inducer staurosporine
      followed by rounds of recovery in fresh medium. The engineered B cells expressing
      Bcl-x(L) exhibited progressively lower increases in apoptosis activation as
      measured by caspase-3 activity after successive rounds of selective pressure with
      staurosporine treatment. Within the B-cell genome, a number of mutated bcl-x(L)
      transgene variants were identified after three rounds of evolution, including a
      mutation of Bcl-x(L) Asp29 to either Asn or His, in 8 out of 23 evaluated
      constructs that represented at least five distinct Ramos subpopulations.
      Subsequently, Chinese hamster ovary (CHO) cells engineered to overexpress the Bcl
      x(L) Asp29Asn variant showed enhanced apoptosis resistance against an orthogonal
      apoptosis insult, Sindbis virus infection, when compared with cells expressing
      the wild-type Bcl-x(L) protein. These findings provide, to our knowledge, the
      first demonstration of evolution of a recombinant mammalian protein in a
      mammalian expression system.

PMID- 22160869
TI  - Effect of HSP65 on the expression of adhesion molecules in mice heart endothelial
      cells.
AB  - This study aims to research the effect of HSP65 on the expression of adhesion
      molecules in activated mice heart endothelial cells (MHECs), which were from
      myocardial tissue of newborn animals. We used different concentrations of LPS as
      potent inducers to stimulate MHECs, adhesion molecule expression in vitro,
      including intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule
      1 (VCAM-1), E-, and P-selectins, then compared the mRNA and protein levels of
      adhesion molecules expression with or without HSP65 treatment at different
      levels. The optimal concentration of LPS to induce MHECs adhesion molecule
      expression is 100 ng/ml; HSP65 treatment significantly reduced the mRNA and
      protein levels of MHECs' ICAM-1, VCAM-1, E-, and P-selectins expression (p <
      0.05), and the optimal concentration of HSP65 in inhibiting MHECs activation is
      0.8 ng. HSP65 has the inhibitory effect on adhesion molecules expression in
      activated MHECs.

PMID- 22160870
TI  - The E6 oncoprotein from HPV16 enhances the canonical Wnt/beta-catenin pathway in
      skin epidermis in vivo.
AB  - The contribution of the Wnt signaling pathway to human papilloma virus (HPV)
      induced carcinogenesis is poorly understood. In high-grade dysplastic lesions
      that are caused by high-risk HPVs (HR-HPV), beta-catenin is often located in the
      cell nucleus, which suggests that Wnt pathway may be involved in the development
      of HPV-related carcinomas. Most of the oncogenic potential of HR-HPVs resides on
      the PDZ-binding domain of E6 protein. We hypothesized that the PDZ-binding domain
      of the HPV16-E6 oncoprotein induces the nuclear accumulation of beta-catenin due
      to its capacity to degrade PDZ-containing cellular targets. To test this
      hypothesis, we evaluated the staining pattern of beta-catenin in the skin
      epidermis of transgenic mice expressing the full-length E6 oncoprotein (K14E6
      mice) and measured LacZ gene expression in K14E6 mice that were crossed with a
      strain expressing LacZ that was knocked into the Axin2 locus (Axin2(+/LacZ)
      mice). Here, we show that the E6 oncoprotein enhances the nuclear accumulation of
      beta-catenin, the accumulation of cellular beta-catenin-responsive genes, and the
      expression of LacZ. None of these effects were observed when a truncated E6
      oncoprotein that lacks the PDZ-binding domain was expressed alone (K14E6DeltaPDZ
      mice) or in combination with Axin2(+/LacZ). Conversely, cotransfection with
      either E6 or E6DeltaPDZ similarly enhanced canonical Wnt signaling in short-term
      in vitro assays that used a luciferase Wnt/beta-catenin/TCF-dependent promoter.
      We propose that the activation of canonical Wnt signaling could be induced by the
      HPV16-E6 oncoprotein; however, the participation of the E6 PDZ-binding domain
      seems to be important in in vivo models only.

PMID- 22160871
TI  - With the past behind and the future ahead: back-to-front representation of past
      and future sentences.
AB  - Several studies support the psychological reality of a mental timeline that runs
      from the left to the right and may strongly affect our thinking about time.
      Ulrich and Maienborn (Cognition 117:126-138, 2010) examined the linguistic
      relevance of this timeline during the processing of past- and future-related
      sentences. Their results indicate that the timeline is not activated
      automatically during sentence comprehension. While no explicit reference of
      temporal expressions to the left-right axis has been attested (e.g., *the meeting
      was moved to the left), natural languages refer to the back-front axis in order
      to encode temporal information (e.g., the meeting was moved forward). Therefore,
      the present study examines whether a back-frontal timeline becomes automatically
      activated during the processing of past- and future-related sentences. The
      results demonstrate a clear effect on reaction time that emerges from a time
      space association along the frontal timeline (Experiment 1). However, this
      activation seems to be nonautomatic (Experiment 2), rendering it unlikely that
      this frontal timeline is involved in comprehension of the temporal content of
      sentences.

PMID- 22160872
TI  - The origin of the interaction between learning method and delay in the testing
      effect: the roles of processing and conceptual retrieval organization.
AB  - Recent research has demonstrated a relationship between retrieval organization
      and the efficacy of prior repeated retrieval on delayed tests. The present study
      asked why repeated study engenders higher recall at a short delay despite lower
      retrieval organization but produces a decline at a long delay, and why repeated
      retrieval engenders lower recall at a short delay despite higher retrieval
      organization but produces stable recall over time. This relationship was examined
      through the inclusion of two successive recall tests-one immediately after
      learning method and one a week later. Results replicated the interaction in
      recall between learning method and delay characterizing the testing effect and,
      critically, revealed the qualitative differences inherent in the retrieval
      organization of each method. Specifically, stable recall in repeated retrieval
      was accompanied by strong and sustained conceptual organization, whereas
      organization for repeated study was tenuous and weakened across tests. These
      differences quantitatively were assessed through the use of five targeted
      analyses: specifically, the examination of cumulative recall curves, the
      accumulation of organization across time (a curve akin to cumulative recall),
      item gains and losses across time, changes in the size of categories across time,
      and the fate of specific clusters of recalled items across time. These
      differences are discussed within the context of differential processes occurring
      during learning method.

PMID- 22160873
TI  - Semantic predictability eliminates the transposed-letter effect.
AB  - Semantic predictability facilitates word recognition during language processing.
      One possible explanation for this facilitation is that highly specific
      predictions generated online during language processing preactivate some features
      of upcoming words. To explore whether, how, and when these predictions affect
      visual word recognition, in the two experiments reported here we investigated the
      influence of semantic predictability on transposed-letter priming. In order to do
      so, a paradigm that combines self-paced word-by-word reading with masked priming
      was developed. Transposed-letter priming occurred in nonconstraining contexts but
      not in constraining contexts, indicating that readers use context to make
      predictions about both letter identity and position in upcoming words, and that
      these predictions have an early influence on visual word recognition.

PMID- 22160875
TI  - Dual-labeling strategies for nuclear and fluorescence molecular imaging: a review
      and analysis.
AB  - Molecular imaging is used for the detection of biochemical processes through the
      development of target-specific contrast agents. Separately, modalities such as
      nuclear and near-infrared fluorescence (NIRF) imaging have been shown to non
      invasively monitor disease. More recently, merging of these modalities has shown
      promise owing to their comparable detection sensitivity and benefited from the
      development of dual-labeled imaging agents. Dual-labeled agents hold promise for
      whole-body and intraoperative imaging and could bridge the gap between surgical
      planning and image-guided resection with a single, molecularly targeted agent. In
      this review, we summarized the literature for dual-labeled antibodies and
      peptides that have been developed and have highlighted key considerations for
      incorporating NIRF dyes into nuclear labeling strategies. We also summarized our
      findings on several commercially available NIRF dyes and offer perspectives for
      developing a toolkit to select the optimal NIRF dye and radiometal combination
      for multimodality imaging.

PMID- 22160876
TI  - Germinal center texture entropy as possible indicator of humoral immune response:
      immunophysiology viewpoint.
AB  - PURPOSE: In this article, we present the results indicating that spleen germinal
      center (GC) texture entropy determined by gray-level co-occurrence matrix (GLCM)
      method is related to humoral immune response. PROCEDURES: Spleen tissue was
      obtained from eight outbred male short-haired guinea pigs previously immunized by
      sheep red blood cells (SRBC). A total of 312 images from 39 germinal centers (156
      GC light zone images and 156 GC dark zone images) were acquired and analyzed by
      GLCM method. Angular second moment, contrast, correlation, entropy, and inverse
      difference moment were calculated for each image. Humoral immune response to SRBC
      was measured using T cell-dependent antibody response (TDAR) assay. RESULTS:
      Statistically highly significant negative correlation was detected between light
      zone entropy and the number of TDAR plaque-forming cells (r (s) = -0.86, p <
      0.01). The entropy decreased as the plaque-forming cells increased and vice
      versa. A statistically significant negative correlation was also detected between
      dark zone entropy values and the number of plaque-forming cells (r (s) = -0.69, p
      < 0.05). CONCLUSIONS: Germinal center texture entropy may be a powerful indicator
      of humoral immune response. This study is one of the first to point out the
      potential scientific value of GLCM image texture analysis in lymphoid tissue
      cytoarchitecture evaluation. Lymphoid tissue texture analysis could become an
      important and affordable addition to the conventional immunophysiology
      techniques.

PMID- 22160877
TI  - Promises of PAR-1 inhibition in acute coronary syndrome.
AB  - Platelet activation is a key process in the pathogenesis of acute coronary
      syndromes (ACS). Of the many triggers involved in this process, three are
      presumed to be critical: thromboxane A(2) (TBXA(2)) via the TBXA(2) receptor,
      adenosine diphosphate via the P2Y(12) receptor, and thrombin via the protease
      activated receptor (PAR)-1. Despite the effective inhibition of the first two
      pathways with aspirin and an expanding family of P2Y(12) inhibitors, the
      incidence of recurrent ischemic events remains high after ACS. PAR-1 inhibitors
      are a novel class of antiplatelet agents that inhibit thrombin-mediated platelet
      activation. Preclinical data and phase 2 clinical trials in patients with stable
      and unstable coronary disease support the potential of these compounds to improve
      clinical outcome. In this review we discuss the rationale for developing this
      novel class of agents with a focus on the two compounds in most advanced clinical
      development, vorapaxar (SCH 530348) and atopaxar (E5555).

PMID- 22160878
TI  - Tcf7l2 is tightly controlled during myelin formation.
AB  - Recent, studies have shown that Tcf7l2, an important transcription factor in Wnt
      pathway, plays critical roles in oligodendrocyte development. In this article we
      report a study showing that Tcf7l2 is under tight regulation during myelin
      formation. We have found that during early development, Tcf7l2 mRNA appears much
      earlier than the protein, suggesting a regulation at the translational level. We
      induced demyelination in a mouse model by a dietary toxin, where remyelination
      followed after a few weeks, and found that Tcf7l2 protein was expressed
      specifically during the active remyelination phase. Similarly, in human patients
      with demyelination diseases, Tcf7l2 protein expression was specifically promoted
      in regions undergoing active remyelination. During remyelination, Tcf7l2 was only
      expressed in non-dividing oligodendrocyte precursors and was associated with
      modest levels of nuclear beta-catenin. We also documented that Tcf7l2 could form
      protein complex with Olig2, but not with Olig1. Our data showed that during
      myelin formation, Tcf7l2/beta-catenin is regulated temporally, spatially, and
      also at levels of expression. These data suggest a key role for Tcf7l2 in
      myelination/remyelination processes via a tightly controlled activation of
      Wnt/beta-catenin pathway and the interaction with Olig2.

PMID- 22160879
TI  - Dissociation of modular total hip arthroplasty at the neck-stem interface without
      dislocation.
AB  - Modular femoral and acetabular components are now widely used, but only a few
      complications related to the modularity itself have been reported. We describe a
      case of dissociation of the modular total hip arthroplasty (THA) at the femoral
      neck-stem interface during walking. The possible causes of this dissociation are
      discussed. Successful treatment was provided with surgical revision and
      replacement of the modular neck components. Surgeons who use modular components
      in hip arthroplasties should be aware of possible early complications in which
      the modularity of the prostheses is the major factor of failure.

PMID- 22160880
TI  - Differential effect of postnatal lead exposure on gene expression in the
      hippocampus and frontal cortex.
AB  - Although developmental lead exposure is known to have detrimental effects on a
      variety of cognitive functions that depend on the integrity of the hippocampus
      and frontal cortex, little is known about how low levels of lead exposure affect
      expression of key families of genes in these structures. The present study
      examined the effects of exposure to environmentally relevant levels of lead
      during the sensitive early post-weaning period in the rat on the expression
      profiles of a select number of neurobiologically relevant genes (i.e., genes for
      neurotrophic factors, NMDA receptors, metabotropic glutamate receptors, synaptic
      function/plasticity, cell signaling, and transcription/regulation) in the rat
      hippocampus and frontal cortex. Exposure to lead (180 and 375-ppm lead acetate in
      food for 30 days) significantly increased blood lead levels (5.8 to 10.3 MUg/dl)
      and significantly affected expression of many of the genes examined. In many
      instances, lead exposure had different effects on the same gene depending on the
      brain region in which the expression of that gene was examined. Gene expression
      in the frontal cortex was often more sensitive to modification than gene
      expression in the hippocampus. These results suggest that even past infancy,
      exposures to low levels of lead can have significant effects on gene expression
      in the frontal cortex and the hippocampus with the potential to exert long-term
      effects on behavior and cognition.

PMID- 22160882
TI  - Adult baby syndrome and age identity disorder: comment on Kise and Nguyen (2011).

PMID- 22160881
TI  - Sexual touching and difficulties with sexual arousal and orgasm among U.S. older
      adults.
AB  - Little is known about the non-genitally-focused sexual behavior of those
      experiencing sexual difficulties. The objective of this study was to review the
      theory supporting a link between sexual touching and difficulties with sexual
      arousal and orgasm, and to examine associations between these constructs among
      older adults in the United States. The data were from the 2005-2006 National
      Social Life Health and Aging Project, which surveyed 3,005 community-dwelling men
      and women ages 57-85 years. The 1,352 participants who had had sex in the past
      year reported on their frequency of sexual touching and whether there had been a
      period of several months or more in the past year when they were unable to
      climax, had trouble getting or maintaining an erection (men) or had trouble
      lubricating (women). Women also reported how often they felt sexually aroused
      during partner sex in the last 12 months. The odds of being unable to climax were
      greater by 2.4 times (95% CI 1.2-4.8) among men and 2.8 times (95% CI 1.4-5.5)
      among women who sometimes, rarely or never engaged in sexual touching, compared
      to those who always engaged in sexual touching, controlling for demographic
      factors and physical health. These results were attenuated but persisted after
      controlling for emotional relationship satisfaction and psychological factors.
      Similar results were obtained for erectile difficulties among men and subjective
      arousal difficulties among women, but not lubrication difficulties among women.
      Infrequent sexual touching is associated with arousal and orgasm difficulties
      among older adults in the United States.

PMID- 22160883
TI  - In vitro characterization of chitosan gels for buccal delivery of celecoxib:
      influence of a penetration enhancer.
AB  - Celecoxib (Cx) shows high efficacy in the treatment of osteoarthritis and
      rheumatoid arthritis as a result of its high specificity for COX-2, without
      gastrolesivity or interference with platelet function at therapeutic
      concentrations. Besides of anti-inflammatory effects, Cx also has a potential
      role for oral cancer chemoprevention. For these conditions, oral administration
      in long-term treatment is a concern due to its systemic side effects. However,
      local application at the site of injury (e.g., buccal inflammation conditions or
      chemoprevention of oral cancer) is a promising way to reduce its toxicity. In
      this study, the in vitro characterization of mucoadhesive chitosan (CHT) gels
      associated to Azone(r) was assessed to explore the potential buccal mucosal
      administration of Cx in this tissue. Rheological properties of gels were analyzed
      by a rheometer with cone-plate geometry. In vitro Cx release and permeability
      studies used artificial membranes and pig cheek mucosa, respectively.
      Mucoadhesion were measured with a universal test machine. CHT gels (3.0%)
      containing 2.0% or 3.0% Az showed more appropriate characteristics compared to
      the others: pH values, rheology, higher amount of Cx retained in the mucosa, and
      minimal permeation through mucosa, besides the highest mucoadhesion values, ideal
      for buccal application. Moreover, the flux (J) and amounts of drug released
      decreased with increased CHT and Az concentrations. CHT gels (3.0%) associated
      with 2.0% or 3.0% Az may be considered potential delivery systems for buccal
      administration of Cx.

PMID- 22160884
TI  - Miniaturization in pharmaceutical extrusion technology: feeding as a challenge of
      downscaling.
AB  - In recent years, extrusion technology has shifted the focus of pharmaceutical
      research due to versatile applications like pelletization, bioavailability
      improvement or manipulation of solid-state properties of drugs, continuous
      granulation, and the development of novel solid dosage forms. Meanwhile, a major
      effort has been devoted to the miniaturization of equipment in pharmaceutical
      extrusion technology, particularly with regard to the requirements of the
      development of new chemical entities and formulations. In the present study, a
      lab-scale twin-screw extruder was investigated in order to determine the
      limitations imposed by the feeding systems. The wet extrusion process was
      considered as challenging because both a powder and a liquid feeder have to be
      considered. Initially, the accuracy and uniformity of the powder and liquid
      feeder were tested independently of the extrusion process. After modification of
      the powder feeder, both feeders were investigated in conjunction with extrusion.
      Based on this, an optimization of the liquid feeder was required and completed.
      Both feeder modifications reduced the variability of the moisture content in the
      extrudates 10-fold. This led to a reliable small-scale extrusion process.

PMID- 22160885
TI  - Nano-intercalated organophosphorus-hydrolyzing enzymes in organophosphorus
      antagonism.
AB  - A dendritic poly(2-alkyloxazoline)-based polymer was studied as a new carrier
      system for the organophosphorus-hydrolyzing recombinant enzymes, organophosphorus
      acid anhydrolase and organophosphorus hydrolase. Paraoxon (PO) and
      diisopropylfluorophosphate (DFP) were used as model organophosphorus compounds.
      Changes in plasma cholinesterase activity were monitored. The cholinesterase
      activity was proportional to the concentrations of DFP or PO. Plasma
      cholinesterase activity was higher in animals receiving enzyme and oxime before
      the organophosphates than in the oxime-only pretreated groups. These studies
      suggest that cholinesterase activity can serve as an indicator for the in vivo
      protection by the nano-intercalated organophosphorus acid anhydrolase or
      organophosphorus hydrolase against organophosphorus intoxications. These studies
      represent a practical application of polymeric nano-delivery systems as enzyme
      carriers in drug antidotal therapy.

PMID- 22160887
TI  - Molecular genetic analysis of Mycobacterium tuberculosis strains spread in
      different patient groups in St. Petersburg, Russia.
AB  - Molecular epidemiological features of Mycobacterium tuberculosis strains among
      different patient groups in Russia have not been studied well. The aim of our
      study was to compare the genotypes of M. tuberculosis strains circulating among
      tuberculosis (TB) patients from different groups: homeless, human
      immunodeficiency virus (HIV)-infected, prisoners, and the general population of
      St. Petersburg citizens. One hundred and forty-two M. tuberculosis complex
      isolates from different TB patient groups were studied using the spacer
      oligonucleotide typing (spoligotyping) method. The majority of the studied M.
      tuberculosis isolates in all groups belonged to the Beijing family (55% among
      homeless; 77% among HIV-infected; 60% among the general population; 81% among
      prisoners). There were no significant differences in the Beijing family
      prevalence among homeless patients, HIV/TB co-infected patients, and the general
      population of TB patients. The lowest genetic diversity of the pathogen was
      detected among imprisoned patients. The results of our study demonstrate that M.
      tuberculosis strains circulating among patients from high-risk groups are also
      spread among the general population of St. Petersburg citizens.

PMID- 22160886
TI  - Preparation, characterization, and in vitro intestinal permeability evaluation of
      thalidomide-hydroxypropyl-beta-cyclodextrin complexes.
AB  - Thalidomide is emerging as a therapeutic agent with renewed clinical importance,
      presenting anti-inflammatory, immunomodulatory, and antineoplasic properties. In
      this work, we studied the complexation of thalidomide with cyclodextrins as a
      strategy to circumvent the poor aqueous solubility of the drug. Thalidomide
      hydroxypropyl-beta-cyclodextrin complexes were obtained by kneading method and
      were characterized by differential scanning calorimetry, powder X-ray
      diffractometry, and scanning electronic microscopy. The aqueous solubility and in
      vitro dissolution of thalidomide were significantly improved through the
      complexation. Physicochemical analysis of the complexes in solid state revealed a
      decreased crystallinity of the complexed drug in comparison with free
      thalidomide. Thalidomide was able to dissociate from the complexes and permeates
      across intestinal epithelial Caco-2 cells with a favorable high permeability
      profile equivalent to that of the free drug. In summary, the present results
      suggest that thalidomide-hydroxypropyl-beta-cyclodextrin complexes could be
      regarded as a promising strategy for improving the gastrointestinal absorption of
      thalidomide.

PMID- 22160888
TI  - Safety analysis of high dose (>6 mg/kg/day) daptomycin in patients with
      concomitant statin therapy.
AB  - There is a paucity of data regarding efficacy and safety of concomitant therapy
      of daptomycin and statins, so we reviewed patients that concomitantly received
      daptomycin and statins to identify any potential increase in toxicity in our
      cohort. This retrospective study included all patients that received >6 mg/kg/day
      of daptomycin along with statins and had efficacy and safety data. Patients on
      high dose (>6 mg/kg/day) daptomycin therapy that did not received statins served
      as controls. One hundred four patients were included. Median daptomycin dose was
      7.8 mg/kg/day (range 6.5-10.8 mg/kg/day), for a mean duration of therapy of 17
      days (range 10-51 days). Thirty-six patients received daptomycin and statins and
      68 received only daptomycin. Muscular toxicity defined as CPK levels>1000 UI/L
      (2.5 times upper normal limit, range of determination 200-400 UI/L) was equally
      distributed between both groups (3/36, 8% vs 7/68, 10%; p=0.746). Despite
      biochemical toxicity, we did not find clinical toxicity and daptomycin treatment
      was completed in all cases. We did not find predictors of increased CPK during
      daptomycin therapy. Based on our data, concomitant administration of daptomycin
      and statins is safe and is not associated with an increased risk of
      rhabdomyolysis.

PMID- 22160890
TI  - Improvement happens: an interview with Deeb Salem, MD and Brian Cohen, MD.

PMID- 22160889
TI  - How safe is your neighborhood? Perceived neighborhood safety and functional
      decline in older adults.
AB  - BACKGROUND: Neighborhood characteristics are associated with health and the
      perception of safety is particularly important to exercise and health among older
      adults. Little is known about the relationship between perception of neighborhood
      safety and functional decline in older adults. OBJECTIVE: To determine the
      relationship between perceived neighborhood safety and functional decline in
      older adults. DESIGN/SETTING: Longitudinal, community-based. PARTICIPANTS: 18,043
      persons, 50 years or older, who participated in the 1998 and 2008 Health and
      Retirement Study. MAIN MEASURES: The primary outcome was 10-year functional
      decline (new difficulty or dependence in any Activity of Daily Living, new
      mobility difficulty, and/or death). The primary predictor was perceived
      neighborhood safety categorized into three groups: "very safe", "moderately
      safe", and "unsafe." We evaluated the association between perceived neighborhood
      safety and 10-year functional decline using a modified Poisson regression to
      generate unadjusted and adjusted relative risks (ARR). KEY RESULTS: At baseline
      11,742 (68.0%) participants perceived their neighborhood to be very safe, 4,477
      (23.3%) moderately safe, and 1,824 (8.7%) unsafe. Over 10 years, 10,338 (53.9%)
      participants experienced functional decline, including 6,266 (50.2%) who had
      perceived their neighborhood to be very safe, 2,839 (61.2%) moderately safe, and
      1,233 (63.6%) unsafe, P < 0.001. For the 11,496 (63.3%) of participants who were
      functionally independent at baseline, perceived neighborhood safety was
      associated with 10-year functional decline (moderately safe ARR 1.15 95% CI 1.09
      1.20; unsafe ARR 1.21 95% CI: 1.03-1.31 compared to very safe group). The
      relationship between perceived neighborhood safety and 10-year functional decline
      was not statistically significant for participants who had baseline functional
      impairment. CONCLUSION: Asking older adults about their perceived neighborhood
      safety may provide important information about their risk of future functional
      decline. These findings also suggest that future studies might focus on assessing
      whether interventions that promote physical activity while addressing safety
      concerns help reduce functional decline in older adults.

PMID- 22160891
TI  - Using folding promoting agents in recombinant protein production: a review.
AB  - Recombinant production has become an invaluable tool for supplying research and
      therapy with proteins of interest. The target proteins are not in every case
      soluble and/or correctly folded. That is why different production parameters such
      as host, cultivation conditions and co-expression of chaperones and foldases are
      applied in order to yield functional recombinant protein. There has been a
      constant increase and success in the use of folding promoting agents in
      recombinant protein production. Recent cases are reviewed and discussed in this
      chapter. Any impact of such strategies cannot be predicted and has to be analyzed
      and optimized for the corresponding target protein. The in vivo effects of the
      agents are at least partially comparable to their in vitro mode of action and
      have been studied by means of modern systems approaches and even in combination
      with folding/activity screening assays. Resulting data can be used directly for
      experimental planning or can be fed into knowledge-based modelling. An overview
      of such technologies is included in the chapter in order to facilitate a decision
      about the potential in vivo use of folding promoting agents.

PMID- 22160892
TI  - Routine identity confirmation of recombinant proteins by MALDI-TOF mass
      spectrometry.
AB  - Peptide mass fingerprinting (PMF) by matrix-assisted laser-desorption ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) provides a simple and direct
      means to unequivocally confirm identity of recombinant proteins based on
      predicted peptide profiles. Many universities or research institutions now carry
      mass spectrometry instrumentation as part of their core bioanalytical facilities
      or provide public service to outside investigators. This chapter provides methods
      we have used to generate routinely high quality samples for MALDI-TOF MS
      analysis. Following resolution of protein preparations by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), we easily process sets of 12
      samples manually for MS analysis. Target bands are alkylated and digested in-gel
      with trypsin, followed by extraction of peptides and desalting with a C18
      adsorbent resin (e.g., a "ZipTips"). Acquisition of PMF data on MALDI-TOF mass
      spectrometers is fast, and with on-site instrumentation, the entire process can
      be completed within 2 days.

PMID- 22160893
TI  - A matter of packaging: influence of nucleosome positioning on heterologous gene
      expression.
AB  - The organization of DNA into the various levels of chromatin compaction is the
      main obstacle that restricts the access of transcriptional machinery to genes.
      Genome-wide chromatin analyses have shown that there are common chromatin
      organization patterns for most genes but have also revealed important differences
      in nucleosome positioning throughout the genome. Such chromatin heterogeneity is
      one of the reasons why recombinant gene expression is highly dependent on
      integration sites. Different solutions have been tested for this problem,
      including artificial targeting of chromatin-modifying factors or the addition of
      DNA elements, which efficiently counteract the influence of the chromatin
      environment.An influence of the chromatin configuration of the recombinant gene
      itself on its transcriptional behavior has also been established. This view is
      especially important for heterologous genes since the general parameters of
      chromatin organization change from one species to another. The chromatin
      organization of bacterial DNA proves particularly dramatic when introduced into
      eukaryotes. The nucleosome positioning of recombinant genes is the result of the
      interaction between the machinery of the hosting cell and the sequences of both
      the recombinant genes and the promoter regions. We discuss the key aspects of
      this phenomenon from the heterologous gene expression perspective.

PMID- 22160894
TI  - Tools of the trade: developing antibody-based detection capabilities for
      recombinant proteins.
AB  - Protein-specific antibodies serve as critical tools for detection,
      quantification, and characterization of recombinant proteins. Perhaps the most
      important and widely used antibody-based procedures for recombinant protein
      applications are Western immunoblotting and enzyme-linked immunosorbent assays
      (ELISAs). These analyses require well-characterized, sensitive, and high-affinity
      antibodies that specifically and selectively recognize the recombinant target
      protein in the native or denatured form. Although the number of commercially
      available antibodies is quite substantial and rapidly growing, the appropriate
      antibody tools for many applications currently do not exist. In this chapter,
      strategies to develop and characterize both polyclonal and monoclonal antibodies
      directed against a specific protein of interest are discussed. Experimental
      strategies and methods are presented for producing and selecting the best
      antibodies and optimizing protocols for Western analyses, ELISAs, and other
      applications. Once antibody and procedure optimization is completed to ensure
      specificity, sensitivity, accuracy, and reliability, these immune-based
      approaches can now serve as powerful and enabling tools in the characterization,
      detection and diagnostics, structure/function analysis, and quality assessment of
      recombinant proteins.

PMID- 22160895
TI  - Heat-shock protein fusion vectors for improved expression of soluble recombinant
      proteins in Escherichia coli.
AB  - Molecular chaperones or heat-shock proteins (HSPs) are protein machines that
      interact with unfolded or partially folded polypeptides and assist them in
      attaining their proper conformation. The folding reaction relies on a complex
      array of scaffolding effects and ATP-driven conformational changes that mediate
      the temporary unfolding and subsequent refolding of protein substrates. DnaK and
      GroEL are the two major Escherichia coli chaperones. They belong to the HSP70 and
      HSP60 families of proteins, respectively, and play a major role in protein
      folding. Here, we describe a set of bacterial expression vectors that permits the
      fusion of a protein of interest to DnaK or GroEL and its subsequent quantitative
      expression in a soluble, easily purifiable form. We also provide a set of
      compatible co-chaperone expression constructs that permit the simultaneous co
      expression of the DnaK and GroEL physiological partners to further increase
      protein solubility. The system was successfully tested using the murine prion
      protein (PrP). Although PrP is normally insoluble when expressed in E. coli, we
      show that utilizing our vectors it can be produced in a soluble form as a DnaK or
      GroEL fusion. This system is useful for the production of a large array of
      proteins that fail to fold properly when expressed in E. coli.

PMID- 22160896
TI  - The use of a flagellar export signal for the secretion of recombinant proteins in
      Salmonella.
AB  - The flagellum-specific export system is a specialized type III export machinery,
      which exports external flagellar proteins through the central channel of the
      flagellar filament. A number of evidence indicates that short segments within the
      disordered N-terminal region of flagellar axial proteins are recognized by the
      flagellum-specific export apparatus. Recently, we have demonstrated that the 26
      47 segment of Salmonella typhimurium flagellin is capable of mediating flagellar
      export. N-terminal flagellin segments containing the export signal combined with
      a hexahistidine tag can be attached to heterologous proteins (preferentially in
      the size range of 9-40 kDa) facilitating their secreted expression and easy
      purification from the medium. Certain over-expressed proteins that are easily
      degraded within the cells are found intact in the medium implying a potential
      application of this expression system for proteins of high proteolytic
      susceptibility.

PMID- 22160897
TI  - Optimization of purification protocols based on the step-by-step monitoring of
      the protein aggregates in soluble fractions.
AB  - Soluble protein fractions are often considered containing exclusively
      monodispersed and correctly folded molecules. This is not the case, being soluble
      aggregates of different complexity widely represented in such fractions. The use
      of fusing target protein domains to highly soluble carriers may strongly
      contribute to soluble aggregate accumulation. Therefore, reliable analytical
      methods must be used to evaluate the biophysical characteristics of soluble
      proteins. On the other hand, conventional methodologies are often technically
      demanding and time consuming. In this method paper, a protocol is presented that
      enables the rapid evaluation of the protein monodispersity from the initial step
      aimed at screening several conditions in parallel to the setup of the complete
      protocol for large-scale purification. The analysis is performed by means of
      simple lab equipment and starting from small sample volumes.

PMID- 22160898
TI  - Heterologous protein expression by Lactococcus lactis.
AB  - This chapter describes the use of Lactococcus lactis as a safe and efficient cell
      factory to produce heterologous proteins of medical interest. The relevance of
      the use of this lactic acid bacterium (LAB) is that it is a noncolonizing,
      nonpathogenic microorganism that can be delivered in vivo at a mucosal level. The
      use of strains of L. lactis in clinical trials in humans to alleviate
      inflammatory bowel diseases has opened up the possibility of using this same LAB
      to target other diseases.Several crucial aspects are addressed in this chapter,
      such as the expression of heterologous protein, subcellular compartment into
      which the heterologous protein is located, and description of a standardized
      protocol to process samples in cell and cell-free fractions to detect the
      targeted protein expressed by L. lactis.

PMID- 22160899
TI  - An extended suite of genetic tools for use in bacteria of the Halomonadaceae: an
      overview.
AB  - Halophilic gammaproteobacteria of the family Halomonadaceae (including the genera
      Aidingimonas, Carnimonas, Chromohalobacter, Cobetia, Halomonas, Halotalea,
      Kushneria, Modicisalibacter, Salinicola, and Zymobacter) have current and
      promising applications in biotechnology mainly as a source of compatible solutes
      (powerful stabilizers of biomolecules and cells, with exciting potentialities in
      biomedicine), salt-tolerant enzymes, biosurfactants, and extracellular
      polysaccharides, among other products. In addition, they display a number of
      advantages to be used as cell factories, alternative to conventional prokaryotic
      hosts like Escherichia coli or Bacillus, for the production of recombinant
      proteins: (1) their high salt tolerance decreases to a minimum the necessity for
      aseptic conditions, resulting in cost-reducing conditions, (2) they are very easy
      to grow and maintain in the laboratory, and their nutritional requirements are
      simple, and (3) the majority can use a large range of compounds as a sole carbon
      and energy source. In the last 15 years, the efforts of our group and others have
      made possible the genetic manipulation of this bacterial group. In this review,
      the most relevant and recent tools for their genetic manipulation are described,
      with emphasis on nucleic acid isolation procedures, cloning and expression
      vectors, genetic exchange mechanisms, mutagenesis approaches, reporter genes, and
      genetic expression analyses. Complementary sections describing the influence of
      salinity on the susceptibility of these bacteria to antimicrobials, as well as
      the growth media most routinely used and culture conditions, for these
      microorganisms, are also included.

PMID- 22160900
TI  - Regulated recombinant protein production in the Antarctic bacterium
      Pseudoalteromonas haloplanktis TAC125.
AB  - This review reports results from our laboratory on the development of an
      effective inducible expression system for the homologous/heterologous protein
      production in cold-adapted bacteria. Recently, we isolated and characterized a
      regulative genomic region from Pseudoalteromonas haloplanktis TAC125; in
      particular, a two-component regulatory system was identified. It is involved in
      the transcriptional regulation of the gene coding for an outer membrane porin
      (PSHAb0363) that is strongly induced by the presence of L: -malate in the growth
      medium.We used the regulative region comprising the two-component system located
      upstream the PSHAb0363 gene to construct an inducible expression vector - named
      pUCRP - under the control of L: -malate. Performances of the inducible system
      were tested using the psychrophilic beta-galactosidase from P. haloplanktis TAE79
      as model enzyme to be produced. Our results demonstrate that the recombinant cold
      adapted enzyme is produced in P. haloplanktis TAC125 in good yields and in a
      completely soluble and catalytically competent form. Moreover, an evaluation of
      optimal induction conditions for protein production was also carried out in two
      consecutive steps: (1) definition of the optimal cellular growth phase in which
      the gene expression has to be induced; (2) definition of the optimal inducer
      concentration that has to be added in the growth medium.

PMID- 22160901
TI  - A novel strategy for the construction of genomic mutants of the Antarctic
      bacterium Pseudoalteromonas haloplanktis TAC125.
AB  - The sequencing and the annotation of the marine Antarctic Pseudoalteromonas
      haloplanktis TAC125 genome has paved the way to investigate on the molecular
      mechanisms involved in adaptation to cold conditions. The growing interest in
      this unique bacterium prompted the developing of several genetic tools for
      studying it at the molecular level. To allow a deeper understanding of the
      PhTAC125 physiology a genetic system for the reverse genetics in this bacterium
      was developed. In the present work, we describe a practical technique for allelic
      exchange and/or gene inactivation by in-frame deletion and the use of a
      counterselectable marker in P. haloplanktis. The construction of suitable non
      replicating plasmid and methods used to carry out a two-step integration
      segregation strategy in this bacterium are reported in detail.Furthermore two
      examples, in which the developed methodology was applied to find out gene
      function or to construct genetically engineered bacterial strains, were
      described.

PMID- 22160902
TI  - A new bacterial co-expression system for over-expressing soluble protein and
      validating protein-protein interaction.
AB  - Toxic, membrane, and hydrophobic proteins are usually difficult to individually
      over-express in Escherichia coli because they require a binding-partner protein
      for folding and stability. To obtain these types of soluble proteins or protein
      complexes, protein co-expression is used. Such co-expression systems are
      extremely suitable for the high-throughput validation of protein-protein
      interactions. In a previous study, we developed a novel co-expression vector,
      pHEX, which is compatible, and thus can be partnered, with many commercially
      available E. coli vectors, such as pGEX and pMAL. Either of the vectors allows
      proteins to be expressed individually as a tagged fusion protein and can be used
      directly for protein co-purification. This protocol presents the experimental
      procedure for the co-expression method.

PMID- 22160903
TI  - Heterologous high-level gene expression in the photosynthetic bacterium
      Rhodobacter capsulatus.
AB  - The functional expression of heterologous genes in standard hosts such as
      Escherichia coli is often hampered by various limitations including improper
      folding, incomplete targeting, and missassembly of the corresponding enzymes.
      This observation led to the development of numerous expression systems that are
      based on alternative, metabolic versatile hosts. One such organism is the Gram
      negative phototrophic nonsulfur purple bacterium Rhodobacter capsulatus. During
      photosynthetic growth, R. capsulatus exhibits several unique properties including
      the formation of an intracytoplasmic membrane system as well as the synthesis of
      various metal-containing cofactors. These properties make R. capsulatus a
      promising expression host particularly suited for difficult-to-express proteins
      such as membrane proteins. In this chapter, we describe a novel R. capsulatus
      expression system and its application.

PMID- 22160904
TI  - Plasmid DNA production for therapeutic applications.
AB  - Plasmid DNA (pDNA) is the base for promising DNA vaccines and gene therapies
      against many infectious, acquired, and genetic diseases, including HIV-AIDS,
      Ebola, Malaria, and different types of cancer, enteric pathogens, and influenza.
      Compared to conventional vaccines, DNA vaccines have many advantages such as high
      stability, not being infectious, focusing the immune response to only those
      antigens desired for immunization and long-term persistence of the vaccine
      protection. Especially in developing countries, where conventional effective
      vaccines are often unavailable or too expensive, there is a need for both new and
      improved vaccines. Therefore the demand of pDNA is expected to rise significantly
      in the near future. Since the injection of pDNA usually only leads to a weak
      immune response, several milligrams of DNA vaccine are necessary for immunization
      protection. Hence, there is a special interest to raise the product yield in
      order to reduce manufacturing costs. In this chapter, the different stages of
      plasmid DNA production are reviewed, from the vector design to downstream
      operation options. In particular, recent advances on cell engineering for
      improving plasmid DNA production are discussed.

PMID- 22160905
TI  - Recombinant protein production in the eukaryotic protozoan parasite Leishmania
      tarentolae: a review.
AB  - Leishmania tarentolae is a trypanosomatid protozoan parasite of the gecko, and
      has been established as a new eukaryotic expression system for the production of
      recombinant proteins. It seems that a protozoan parasite is a curious choice as
      the expression host; however, Trypanosomatidae are rich in glycoproteins with a
      pattern of glycosylation closely related to those in mammals and higher
      vertebrates. Thus, one of the main advantages of a L. tarentolae expression
      system is the mammalian-type posttranslational modification of target proteins.
      Although there are few examples of recombinant protein expression using this
      system, it can be an attractive alternative to using mammalian cells. This
      chapter presents an overview of the newly developed protein expression system
      based on L. tarentolae.

PMID- 22160906
TI  - Expression of multisubunit proteins in Leishmania tarentolae.
AB  - Heterologous gene expression in mammalian cells is the first choice for the
      production of recombinant proteins when posttranslational modifications affect
      the biological activity of target proteins. However, the expression efficiency of
      mammalian cells is relatively low compared to other expression systems, such as
      Escherichia coli or yeast. Recently, a novel protein expression system based on
      Leishmania tarentolae, a protozoan parasite of gecko, was developed. This system
      allows not only easy handling like E. coli and yeast, but also full eukaryotic
      protein folding and the mammalian-type posttranslational modifications of target
      proteins. Here, we attempt to produce recombinant human laminin (LM)-332, a large
      heterotrimeric glycoprotein, in the L. tarentolae expression system. A
      recombinant strain harboring three subunits of LM-332 efficiently formed a
      heterotrimer and secreted it into the medium. The purified rLM-332 showed similar
      cell adhesion activity to rLM-332 purified from mammalian cells, indicating its
      proper folding and assembly. In this chapter, we describe a detailed protocol for
      multiple gene expression in the L. tarentolae expression system.

PMID- 22160907
TI  - Recombinant protein production in yeasts.
AB  - Recombinant protein production is a multibillion-dollar market. The development
      of a new product begins with the choice of a production host. While one single
      perfect host for every protein does not exist, several expression systems ranging
      from bacterial hosts to mammalian cells have been established. Among them, yeast
      cell factories combine the advantages of being single cells, such as fast growth
      and easy genetic manipulation, as well as eukaryotic features including a
      secretory pathway leading to correct protein processing and post-translational
      modifications. In this respect, especially the engineering of yeast glycosylation
      to produce glycoproteins of human-like glycan structures is of great interest.
      Additionally, different attempts of cellular engineering as well as the design of
      different production processes that are leading to improved productivities are
      presented. With the advent of cheaper next-generation sequencing techniques,
      systems biotechnology approaches focusing on genome scale analyses will advance
      and accelerate yeast cell factories and thus recombinant protein production
      processes in the near future. In this review we summarize advantages and
      limitations of the main and most promising yeast hosts, including Saccharomyces
      cerevisiae, Pichia pastoris, and Hansenula polymorpha as those presently used in
      large scale production of heterologous proteins.

PMID- 22160908
TI  - Yeasts as a tool for heterologous gene expression.
AB  - The yeasts Saccharomyces cerevisiae and Pichia pastoris are attractive hosts for
      production of human proteins. The main advantages offered by these systems are
      the well-developed and easily accessible genetic tools, rapid growth, the simple
      and inexpensive culture media, and many of the cellular and metabolic processes
      found in higher eukaryotes are conserved in both yeast species. In this chapter,
      we describe the production of two proteins of therapeutic interest: the human P53
      tumor suppressor and the viral HBsAg in P. pastoris and S. cerevisiae using the
      strong and inducible promoters AOX1 and Gal10/Cyc1, respectively. Besides the
      production as a goal of both expressions, we also report on an unexpected result
      that has occurred in S. cerevisiae: The overexpression of human p53 induces yeast
      cell death with characteristic markers of apoptosis, such as the externalization
      of phosphatidylserines and DNA strand cleavage.

PMID- 22160909
TI  - The Cre/lox system: a practical tool to efficiently eliminate selectable markers
      in fungal endophytes.
AB  - Interspecific hybridization is a common evolutionary process for the many
      epichloid fungi that consequently possess multiple gene copies accumulated from
      their parental strains. Serial gene manipulations in such strains are impeded by
      the limited availability of selectable resistance marker genes. Therefore, we
      developed a method for marker elimination suitable for a range of filamentous
      fungi that allows the reuse of the same marker for successive manipulations, and
      can also generate gene knockout mutants free of any foreign genes. For epichloae,
      the complete elimination of the marker gene from the genome would mitigate public
      concerns and regulatory hurdles to the use of such fungal strains in field
      experiments.

PMID- 22160910
TI  - Aptamer-regulated expression of essential genes in yeast.
AB  - Conditional gene expression systems are important tools for the functional
      analysis of essential genes. Tetracycline (tc)-binding aptamers can be exploited
      as artificial riboswitches for the efficient control of gene expression by
      inserting them into the 5' untranslated region of an mRNA. The ligand-bound form
      of those mRNAs inhibits gene expression by interfering with translation
      initiation. In contrast to previous tc-dependent regulatory systems, where tc
      inhibits or activates transcription upon binding to the repressor protein TetR,
      the tc-binding aptamer system inhibits translation of the respective mRNA. We
      describe here a simple and powerful PCR-based strategy which allows easy tagging
      of any target gene in yeast using a tc aptamer-containing insertion cassette. The
      expression window can be adjusted with different promoters and protein synthesis
      is rapidly switched off.

PMID- 22160911
TI  - Cloning and expression of hemicellulases from Aspergillus nidulans in Pichia
      pastoris.
AB  - The methylotrophic yeast Pichia pastoris is increasingly used for heterologous
      expression of high quality proteins in laboratory-scale (milligram) quantities.
      Commercially available polysaccharide-active enzyme preparations have limited
      applications in plant cell wall research due to their heterogeneous mix of
      hydrolytic activities. P. pastoris provides an ideal in vitro expression system
      for producing monocomponent enzymes, since it lacks endogenous plant cell wall
      active enzymes and can perform eukaryotic post-translational modifications (i.e.,
      glycosylation). We have routinely prepared cDNA constructs from Aspergillus
      nidulans encoding a broad array of hydrolases active on various linkages
      contained in plant cell wall polysaccharides. The cDNAs were inserted into the
      pPICZalpha C shuttle vector (Invitrogen) in-frame with the Saccharomyces
      cerevisiae alpha-secretion factor and expressed under the transcriptional control
      of the highly inducible alcohol oxidase 1 (AOX1) promoter. The enzyme products
      were efficiently secreted into buffered complex methanol medium (BMMY) as C
      terminal his-tagged proteins for simple one-step affinity purification. The
      insertion of the c-Myc epitope enabled easy immunodetection. Here we present the
      detailed protocols for primer design, cloning, expression, and activity assays
      for a representative set of xylan-acting hemicellulases produced in P. pastoris.

PMID- 22160912
TI  - A thiamine-regulatable epitope-tagged protein expression system in fission yeast.
AB  - Schizosaccharomyces pombe, the fission yeast, has been a popular and useful model
      system for investigating the mechanisms of biological processes for a long time.
      To facilitate purification, localization, and functional analysis of gene
      products, a wide range of expression vectors have been developed. Several of
      these vectors utilize the inducible/repressible promoter systems and enable the
      episomal expression of proteins as fusion proteins with epitope tags attached to
      their N terminus or C terminus.This chapter provides a detailed protocol for
      expression of the epitope-tagged proteins from thiamine-regulatable nmt promoter
      in fission yeast. The yeast culture conditions and procedures for yeast
      transformation, expression induction, preparation of whole-cell extracts, and
      analysis of epitope-tagged protein expression by Western blotting are described.

PMID- 22160913
TI  - Heterologous gene expression by chromosomal integration in fission yeast.
AB  - Thanks to the convenience and flexibility of the multicopy plasmid-based approach
      for heterologous gene expression, this technique has long been used for
      biological studies, especially in prokaryotes and lower eukaryotes. For better
      understanding of biological mechanisms, however, there are increasing demands on
      the experimental technologies enabling fine-tuned expression of introduced
      heterologous genes or serving conditions that are closer to the physiological
      conditions. For this purpose, the use of direct tagging of a chromosomal gene has
      been gradually increasing, although the use conditions of this approach are
      relatively limited compared to plasmid-based methods. Expression of a cloned gene
      using chromosomal integration has a property intermediate between multicopy
      plasmid-based method and direct tagging of an endogenous gene. Here, we describe
      the principle and methods of introduction of a cloned gene into the targeting
      loci of the chromosome in fission yeast.

PMID- 22160914
TI  - Genetic engineering of industrial strains of Saccharomyces cerevisiae.
AB  - Genetic engineering has been successfully applied to Saccharomyces cerevisiae
      laboratory strains for different purposes: extension of substrate range,
      improvement of productivity and yield, elimination of by-products, improvement of
      process performance and cellular properties, and extension of product range. The
      potential of genetically engineered yeasts for the massive production of biofuels
      as bioethanol and other nonfuel products from renewable resources as
      lignocellulosic biomass hydrolysates has been recognized. For such applications,
      robust industrial strains of S. cerevisiae have to be used. Here, some relevant
      genetic and genomic characteristics of industrial strains are discussed in
      relation to the problematic of the genetic engineering of such strains. General
      molecular tools applicable to the manipulation of S. cerevisiae industrial
      strains are presented and examples of genetically engineered industrial strains
      developed for the production of bioethanol from lignocellulosic biomass are
      given.

PMID- 22160915
TI  - Recombinant protein production in plants: challenges and solutions.
AB  - In a recent presentation at the 2010 International Association for Plant
      Biotechnology meeting, Dr. Richard Flavell (Ceres, Malibu, CA, USA) motivated the
      plant community to act quickly and with purpose to move a multitude of traits
      into crop plants to improve their productivity. Current progress toward
      understanding of plants is too slow and will not achieve our communal goal of
      doubling agricultural productivity by 2050. Major breakthroughs are necessary!
      Thus, high-throughput methods that couple gene identification and phenotype
      observations are required to put potential products into the hands of plant
      breeders to make varieties with good agronomic characteristics that will be
      approved by the regulatory agencies. These first improved crops must be on the
      market in the next 10 years, according to Flavell, in order to begin to meet our
      doubled productivity goals in 30 years. Because it takes approximately 10 years
      to produce a characterized variety from an identified gene and move it through
      product development and regulatory approval, we must begin now. Presumably, by
      employing the techniques in the following -chapters, we can do that.

PMID- 22160916
TI  - A novel plant cell bioproduction platform for high-yield secretion of recombinant
      proteins.
AB  - Plant cell suspension culture integrates the merits of whole-plant systems with
      those of microbial fermentation and mammalian cell culture, and has been
      recognized as a promising alternative biosynthetic platform for valuable
      proteins. However, the low protein productivity dilemma has been the bottleneck
      toward commercializing this technology. Here, we describe a new technology,
      termed hydroxyproline (Hyp)-Glyco technology, that dramatically increases the
      yield of secreted recombinant proteins from cultured plant cells by expressing
      them as fusions with a novel glycomodule tag comprising an Hyp-rich repetitive
      peptide (HypRP) backbone that is subsequently glycosylated through the Hyp
      residues. The extensive glycosylation of the HypRP tags greatly extends the serum
      half-life of small therapeutic proteins, such as interferon alpha2b or human
      growth hormone, without significantly impairing their bioactivities and the tag
      greatly enhances solubility.

PMID- 22160917
TI  - Super-promoter:TEV, a powerful gene expression system for tobacco hairy roots.
AB  - In order to identify a promoter system for high-level expression of transgenes in
      hairy roots, we characterized the chimeric super-promoter fused to the
      translational enhancer from tobacco etch virus (TEV). Transgenic tobacco plants
      and hairy roots were generated with the super-promoter:TEV sequence and a
      modified green fluorescence protein (mGFP5) as a reporter gene. To exploit the
      utility of hairy root cultures as a secretion-based expression system, the signal
      peptide of patatin was fused to mGFP5 to direct its secretion into the culture
      medium. Levels of mGFP5 RNA were on average sixfold higher in hairy roots than
      leaves. Likewise, GFP protein levels per gram of fresh weight were at least
      tenfold higher in hairy roots than leaves. Furthermore, more than 10% of the
      recombinant protein produced in the hairy root culture system was found in the
      medium. Immunoblotting with anti-GFP antibodies showed two products of 27.1 and
      29.9 kDa in all leaf and hairy root tissue extracts, whereas a single 27.1-kDa
      product was detected in the medium. Inducibility of the promoter was studied with
      mature leaves and 14-day (midlog phase) hairy roots. A twofold increase in mRNA
      levels was found immediately after wounding in both mature leaves and hairy
      roots, with a corresponding increase in mGFP5 protein after 24 h. Our studies
      demonstrate the utility of the super-promoter:TEV system for high-level
      expression of recombinant proteins in hairy root bioreactors.

PMID- 22160918
TI  - Bioseparation of recombinant proteins from plant extract with hydrophobin fusion
      technology.
AB  - Two main hurdles hinder the widespread acceptance of plants as a preferred
      protein expression platform: low accumulation levels and expensive
      chromatographic purification methods. Fusion of proteins of interest to fungal
      hydrophobins has provided a tool to address both accumulation and purification
      issues. In this method, we describe the one-step purification of a GFP-HFBI
      fusion from crude plant extract using an aqueous two-phase system (ATPS). ATPS
      can be carried out in a very short time frame, yields relatively pure protein
      with very few contaminants, and does not require any chromatographic column
      steps. This purification system takes advantage of the affinity of hydrophobins
      to the micellar phase of widely available nonionic surfactants, such as Triton X
      114, and can be easily scaled up for industrial-scale protein purification.

PMID- 22160919
TI  - Quality assessment of recombinant proteins produced in plants.
AB  - Plant-based expression technologies for recombinant proteins have begun to
      receive acceptance for pharmaceuticals and other commercial markets. Protein
      products derived from plants offer safer, more cost-effective, and less capital
      intensive alternatives to traditional manufacturing systems using microbial
      fermentation or animal cell culture bioreactors. Moreover, plants are now known
      to be capable of expressing bioactive proteins from a diverse array of species
      including animals and humans. Methods development to assess the quality and
      performance of proteins manufactured in plants are essential to support the QA/QC
      demands as plant-produced protein products transition to the commercial
      marketplace. Within the pharmaceutical arena, process validation and acceptance
      criteria for biological products must comply with the Food and Drug
      Administration (FDA) and ICH Q6B guidelines in order to initiate the regulatory
      approval process. Detailed product specifications will also need to be developed
      and validated for plant-made proteins for the bioenergy, food, chemical
      synthesis, or research reagent markets.We have, therefore, developed assessment
      methods for important qualitative and quantitative parameters of the products and
      the manufacturing methods utilized in plant-based production systems. In this
      chapter, we describe a number of procedures to validate product identity and
      characteristics including mass analyses, antibody cross-reactivity, N-terminal
      sequencing, and bioactivity. We also address methods for routine assessment of
      yield, recovery, and purity. The methods presented are those developed for the
      synthesis and recovery of the avian cytokine, chicken interleukin-12 (ChIL-12),
      produced in the leaves of Nicotiana benthamiana. The ChIL-12 protein used as a
      model for this chapter includes a C-terminal histidine epitope (HIS-tag) and,
      thus, these methods may be directly applicable to other HIS-tagged proteins
      produced in plants. However, the overall strategy presented using the ChIL
      12(HIS) example should provide the basis of standard procedures for assessing the
      quality of other plant-based protein products and manufacturing systems.

PMID- 22160920
TI  - Cell-free protein synthesis as a promising expression system for recombinant
      proteins.
AB  - Cell-free protein synthesis (CFPS) has major advantages over traditional cell
      based methods in the capability of high-throughput protein synthesis and special
      protein production. During recent decades, CFPS has become an alternative protein
      production platform for both fundamental and applied purposes. Using Renilla
      luciferase as model protein, we describe a typical process of CFPS in wheat germ
      extract system, including wheat germ extract preparation, expression vector
      construction, in vitro protein synthesis (transcription/translation), and target
      protein assay.

PMID- 22160921
TI  - The use of bacterial artificial chromosomes for recombinant protein production in
      mammalian cell lines.
AB  - The choice of an expression vector is a critical step in the field of recombinant
      protein production in mammalian cells lines. Most expression vectors used in the
      field are sensitive to the surrounding chromatin to their integration site into
      the host genome cell. This so-called chromatin positional effects influences the
      expression levels of the transgene and tends to silence its expression over time.
      Bacterial artificial chromosomes (BACs) are vectors that can accommodate inserts
      of up to 400 kb. Due to the large cloning capacity, BACs can harbour an entire
      locus with all or most of the regulatory elements controlling the expression of a
      gene. Therefore, BACs contain their own natural chromatin domain and are
      subjected to chromatin positional effects to a lesser extend or not at all. This
      makes cell lines generated with BAC-based expression vectors more predictable in
      terms of protein production and stability. In this chapter, we explore the use of
      BACs as expression vectors for recombinant protein production in mammalian cells.

PMID- 22160922
TI  - Engineering the chaperone network of CHO cells for optimal recombinant protein
      production and authenticity.
AB  - All proteins fold into a defined three-dimensional shape that is compatible with
      the cellular role and/or biological activity of those proteins. Molecular
      chaperones are a family of proteins whose role is to assist the folding and
      targeting of proteins in both normal and stressed cells. The rational
      manipulation of chaperone levels in a cell line engineered to produce a defined
      recombinant protein (rP) can significantly improve both the achievable steady
      state levels and authenticity of a wide range of recombinant proteins. Here, we
      describe the methodology associated with expressing a variety of molecular
      chaperones in Chinese hamster ovary (CHO) lines in order to improve their
      recombinant protein production capacity. These chaperones include both those that
      facilitate the folding of the polypeptide chain (i.e. Hsp70, Hsp40) and those
      that can re-fold proteins that have misfolded in the cell (i.e. ClpB/Hsp104).
      This latter property is particularly important given the propensity for highly
      expressed recombinant proteins to misfold in the "foreign" cellular environment.

PMID- 22160923
TI  - High-throughput baculovirus expression in insect cells.
AB  - Historically, it has been proved difficult to adapt the traditional baculovirus
      expression systems to an automated platform because of the complexity of the
      processes involved. One of the major bottlenecks is the selection of recombinant
      from parental viruses. We have developed a bacmid vector (flashBACTM) that does
      not require any form of selection pressure to separate recombinant virus from
      nonrecombinant parental virus. The method relies on homologous recombination in
      insect cells between a transfer plasmid containing the gene of interest and a
      replication-deficient bacmid. The gene of interest replaces the bacterial
      replicon at the polyhedrin locus, simultaneously restoring a virus gene essential
      for replication, and as only recombinant virus can replicate, no further
      separation techniques are required. This chapter describes methods for producing
      and expression testing multiple recombinant baculoviruses on automated platforms
      using the flashBAC system.

PMID- 22160924
TI  - Recombinant protein expression in milk of livestock species.
AB  - Producing complex recombinant proteins in the milk of transgenic animals offers
      several advantages: large amounts of proteins can be obtained, and in most cases,
      these proteins are properly folded, assembled, cleaved, and glycosylated. The
      level of expression of foreign genes in the mammalian gland cannot be predicted
      in all cases, and appropriate vectors must be used. The main elements of these
      vectors are as follows: a well-characterized specific promoter, the coding region
      of the gene of interest, preferably with a homologous or heterologous intron, to
      improve transcription efficiency, and an insulator or boundary element to
      counteract the chromosomal position effects at the integration site. Once high
      expression levels are achieved, and the recombinant protein is purified, an
      essential step in the analysis of the final product is determining its degree of
      glycosylation. This is an important readout because it can affect among other
      parameters the stability and immunogenicity of the recombinant protein.

PMID- 22160925
TI  - Isolation and characterization of stem-like cells from a human ovarian cancer
      cell line.
AB  - Increasing evidence supports the existence of a subpopulation of cancer cells
      capable of self-renewal and differentiation into diverse cell lineages. These
      cancer stem-like or cancer-initiating cells (CICs) also demonstrate resistance to
      chemo- and radiotherapy and may function as a primary source of cancer
      recurrence. We report here on the isolation and in vitro propagation of
      multicellular ovarian cancer spheroids from a well-established ovarian cancer
      cell line (OVCAR-3). The spheroid-derived cells (SDCs) display self-renewal
      potential, the ability to produce differentiated progeny, and increased
      expression of genes previously associated with CICs. SDCs also demonstrate higher
      invasiveness, migration potential, and enhanced resistance to standard anticancer
      agents relative to parental OVCAR-3 cells. Furthermore, SDCs display up
      regulation of genes associated with epithelial-to-mesenchymal transition (EMT),
      anticancer drug resistance and/or decreased susceptibility to apoptosis, as well
      as, down-regulation of genes typically associated with the epithelial cell
      phenotype and pro-apoptotic genes. Pathway and biological process enrichment
      analyses indicate significant differences between the SDCs and precursor OVCAR-3
      cells in TGF-beta-dependent induction of EMT, regulation of lipid metabolism,
      NOTCH and Hedgehog signaling. Collectively, our results indicate that these SDCs
      will be a useful model for the study of ovarian CICs and for the development of
      novel CIC-targeted therapies.

PMID- 22160927
TI  - A retrospective evaluation of radiation dose associated with low dose FDG
      protocols in whole-body PET/CT.
AB  - The objective of the study is to retrospectively measure patient radiation dose
      resulting from whole body X-ray CT and FDG PET studies using a low-dose protocol
      performed on the Siemens Biograph mCT scanner. A total of 483 patient studies
      were reviewed. For each, the CT dose-length product was used to estimate
      radiation dose to the patient as a result of the whole body X-ray CT component of
      the PET/CT study. The net injected FDG dose was used to calculate the whole body
      effective dose based on ICRP recommendations. Dose calculations were also
      modified to take into account individual patient weight. The total effective dose
      received by each patient was taken as the sum of the PET and CT components of the
      study. The mean effective dose from the CT component of the diagnostic study was
      found to be 8.2 mSv (3.4-23.4 mSv), for a CT protocol of 120 kV(p) and effective
      tube current-time product of 80 mAs with automatic exposure control. For an
      average injected FDG activity of 304 MBq the mean PET effective dose was found to
      be 6.3 mSv when using the ICRP standard models, or 6.0 mSv when scaling effective
      dose to individual patient weight or patient blood volume. The average total
      effective dose across the entire patient cohort for a combined PET/CT study was
      found to be ~14.5 mSv (9.6-29.8 mSv). Low-dose protocols for whole-body PET/CT
      scanning result in an effective radiation dose to the patient of approximately
      14.5 mSv. Additional reductions through the use of iterative CT reconstruction
      and optimized low-dose FDG protocols could see total effective doses for whole
      body PET/CT fall to below 10 mSv.

PMID- 22160926
TI  - Stimulation of mechano-growth factor expression by myofibrillar proteins in
      murine myoblasts and myotubes.
AB  - Mechano-growth factor (MGF) is a product of alternative splicing of the insulin
      like growth factor 1 (IGF-1) mRNA. MGF is known to stimulate myoblast
      proliferation and to protect neurons and cardiomyocytes from apoptosis. MGF
      expression is dramatically increased in response to mechanical stimuli and tissue
      damage. The mechanisms of induction of MGF expression are as yet imperfectly
      understood. There is certain evidence that some protein factors able to stimulate
      MGF synthesis in normal myoblasts are released from damaged muscle. This study
      was undertaken to explore the nature of these protein inductors of MGF expression
      and to investigate the mechanism of their action. We report here that
      myofibrillar fraction of skeletal muscle homogenate activated MGF expression in
      murine myoblasts and myotubes in culture. The expression of another splice form
      of IGF-1 gene, IGF-1Ea, was also stimulated by myofibrils. Three myofibrillar
      proteins able to stimulate MGF synthesis were isolated. These proteins were
      identified by MALDI and immunoblotting as myomesin, myosin-binding protein C, and
      titin. The activation of MGF expression was associated with the increase of cAMP
      level in the cells. Inhibitor of adenylyl cyclase dideoxyadenosine arrested
      stimulation of MGF synthesis by all three myofibrillar proteins.

PMID- 22160928
TI  - Therapeutic effect of Withania somnifera on pristane-induced model of SLE.
AB  - Systemic lupus erythematosus commonly known as lupus is an intricate disorder
      with multiple organ involvement characterized primarily by inflammation caused
      due to deposition of immune-complexes formed by production of autoantibodies
      against nuclear, nucleolar as well as cytoplasmic self-antigens. Lack of
      availability of suitable treatments or treatments that are only symptomatic calls
      for investigation of possible modalities. Withania somnifera with its
      immunomodulatory properties is prescribed for arthritis in ayurveda. In the
      present study, the therapeutic effect of Withania somnifera pure root powder (at
      1,000 and 500 mg/kg body weight) on pristane-induced Balb/c model of lupus was
      investigated to elucidate its remedial outcome on SLE. SLE-like symptoms are
      produced in the model of lupus: production of autoantibodies, proteinuria,
      nephritis as well as immune-complex deposition along with various other
      inflammatory markers such as formation of lipogranuloma, production of pro
      inflammatory cytokines including interleukin-6 and tumor necrosis factor-alpha,
      nitric oxide and reactive oxygen species. Withania somnifera was found to have
      potent inhibitory effect on proteinuria, nephritis and other inflammatory
      markers. Humoral response, however, was found to be impervious. The potent
      reduction in inflammation in the present model of lupus suggests further
      investigation of this herb for its possible therapeutic use in SLE.

PMID- 22160929
TI  - High-level secretion of recombinant monomeric murine and human single-chain Fv
      antibodies from Drosophila S2 cells.
AB  - Single-chain variable fragment (scFvs) antibodies are small polypeptides (~26 kD)
      containing the heavy (V(H)) and light (V(L)) immunoglobulin domains of a parent
      antibody connected by a flexible linker. In addition to being frequently used in
      diagnostics and therapy for an increasing number of human diseases, scFvs are
      important tools for structural biology as crystallization chaperones. Although
      scFvs can be expressed in many different organisms, the expression level of an
      scFv strongly depends on its particular amino acid sequence. We report here a
      system allowing for easy and efficient cloning of (i) scFvs selected by phage
      display and (ii) individual heavy and light chain sequences from hybridoma cDNA
      into expression plasmids engineered for secretion of the recombinant fragment
      produced in Drosophila S2 cells. We validated the method by producing five scFvs
      derived from human and murine parent antibodies directed against various
      antigens. The production yields varied between 5 and 12 mg monomeric scFv per
      liter of supernatant, indicating a relative independence on the individual
      sequences. The recombinant scFvs bound their cognate antigen with high affinity,
      comparable with the parent antibodies. The suitability of the produced
      recombinant fragments for structural studies was demonstrated by crystallization
      and structure determination of one of the produced scFvs, derived from a broadly
      neutralizing antibody against the major glycoprotein E2 of the hepatitis C virus.
      Structural comparison with the Protein Data Bank revealed the typical spatial
      organization of V(H) and V(L) domains, further validating the here-reported
      expression system.

PMID- 22160931
TI  - Cognitive behavioral therapy for institutionalized elders complaining of sleep
      disturbance in Alexandria, Egypt.
AB  - BACKGROUND: Behavioral interventions such as cognitive behavioral therapy (CBT)
      are among the most widely used nonpharmacologic alternatives for the treatment of
      insomnia. PURPOSE: The aim of this study was to determine the prevalence of
      insomnia, factors affecting it, and the impact of a cognitive behavioral therapy
      for institutionalized elders complaining of sleep disturbance in Alexandria,
      Egypt. METHODS: This study was done through two phases. A cross-sectional design
      was used in the first phase to detect the prevalence of sleep problems and their
      correlates among the elderly, then pretest-posttest design was used to apply an
      intervention program to the elders who suffered from insomnia. A pre-designed
      structured interview questionnaire was presented to the participants. The main
      outcome measure was sleep quality, as measured by the Pittsburgh Sleep Quality
      Index. RESULTS: The study included a total of 210 elders (97 males and 113
      females), with a mean age of 72.2 +/- 5.3 years, about two thirds of them were
      poor sleepers (63.3%). The results show that after carrying out the behavioral
      therapy for the elders, the percentage of poor sleepers decreased from 63.3% to
      46.2%. Two variables (educational level and female sex) proved to be
      statistically significantly related to the improvement in sleep quality.
      CONCLUSIONS: A goal of this intervention program was considerably achieved.
      Importantly, the intervention appears to improve sleep quality among the elders.
      Data from this study re-enforce the continuing need for more sleep educational
      programs that are intended to attract the attention of elders especially those
      institutionalized.

PMID- 22160930
TI  - Constitutive K-RasG12D activation of ERK2 specifically regulates 3D invasion of
      human pancreatic cancer cells via MMP-1.
AB  - Pancreatic ductal adenocarcinomas (PDAC) are highly invasive and metastatic
      neoplasms commonly unresponsive to current drug therapy. Overwhelmingly, PDAC
      harbors early constitutive, oncogenic mutations in K-Ras(G12D) that exist prior
      to invasion. Histologic and genetic analyses of human PDAC biopsies also exhibit
      increased expression of extracellular signal-regulated kinase (ERK) 1/2 and
      proinvasive matrix metalloproteinases (MMP), indicators of poor prognosis.
      However, the distinct molecular mechanisms necessary for K-Ras/ERK1/2 signaling
      and its influence on MMP-directed stromal invasion in primary human pancreatic
      ductal epithelial cells (PDEC) have yet to be elucidated in three-dimensions.
      Expression of oncogenic K-Ras(G12D) alone in genetically defined PDECs reveals
      increased invadopodia and epithelial-to-mesenchymal transition markers, but only
      when cultured in a three-dimensional model incorporating a basement membrane
      analog. Activation of ERK2, but not ERK1, also occurs only in K-Ras(G12D)-mutated
      PDECs cultured in three-dimensions and is a necessary intracellular signaling
      event for invasion based upon pharmacologic and short hairpin RNA (shRNA)
      inhibition. Increased active invasion of K-Ras(G12D) PDECs through the basement
      membrane model is associated with a specific microarray gene expression signature
      and induction of MMP endopeptidases. Specifically, MMP-1 RNA, its secreted
      protein, and its proteolytic cleavage activity are amplified in K-Ras(G12D) PDECs
      when assayed by real-time quantitative PCR, ELISA, and fluorescence resonance
      energy transfer (FRET). Importantly, shRNA silencing of MMP-1 mimics ERK2
      inhibition and disrupts active, vertical PDEC invasion. ERK2 isoform and MMP-1
      targeting are shown to be viable strategies to attenuate invasion of K-Ras(G12D)
      mutated human pancreatic cancer cells in a three-dimensional tumor
      microenvironment.

PMID- 22160932
TI  - Protective function of nicotinamide against ketamine-induced apoptotic
      neurodegeneration in the infant rat brain.
AB  - During development, anesthetics activate neuroapoptosis and produce damage in the
      central nervous system that leads to several types of neurological disorders. A
      single dose of ketamine (40 mg/kg) during synaptogenesis in a 7-day-old rat brain
      activated the apoptotic cascade and caused extensive neuronal cell death in the
      forebrain. In this study, we investigated the protective effect of nicotinamide
      against ketamine-induced apoptotic neurodegeneration. After 4 h, neuronal cell
      death induced by ketamine was associated with the induction of Bax, release of
      cytochrome c into the cytosol, and activation of caspase-3. One single dose of 1
      mg/g nicotinamide was administered to a developing rat and was found to inhibit
      ketamine-induced neuroapoptosis by downregulating Bax, inhibiting cytochrome c
      release from mitochondria into cytosol, and inhibiting the expression of
      activated caspase-3. TUNEL and immunohistochemical analyses showed that ketamine
      induced cell death occurred through apoptosis and that it was inhibited by
      nicotinamide. Fluoro-Jade-B staining demonstrated an increased number of dead
      cells in the cortex and thalamus after ketamine treatment; treatment with
      nicotinamide reduced the number of dead cells in these brain regions. Our
      findings suggest that nicotinamide attenuated ketamine-induced neuronal cell loss
      in the developing rat brain and is a promising therapeutic and neuroprotective
      agent for the treatment of neurodevelopmental disorders.

PMID- 22160934
TI  - Predictors of adherence with self-care guidelines among persons with type 2
      diabetes: results from a logistic regression tree analysis.
AB  - Type 2 diabetes is known to contribute to health disparities in the U.S. and
      failure to adhere to recommended self-care behaviors is a contributing factor.
      Intervention programs face difficulties as a result of patient diversity and
      limited resources. With data from the 2005 Behavioral Risk Factor Surveillance
      System, this study employs a logistic regression tree algorithm to identify
      characteristics of sub-populations with type 2 diabetes according to their
      reported frequency of adherence to four recommended diabetes self-care behaviors
      including blood glucose monitoring, foot examination, eye examination and HbA1c
      testing. Using Andersen's health behavior model, need factors appear to dominate
      the definition of which sub-groups were at greatest risk for low as well as high
      adherence. Findings demonstrate the utility of easily interpreted tree diagrams
      to design specific culturally appropriate intervention programs targeting sub
      populations of diabetes patients who need to improve their self-care behaviors.
      Limitations and contributions of the study are discussed. 

PMID- 22160935
TI  - Ribosome inactivating proteins from plants inhibiting viruses.
AB  - Many plants contain ribosome inactivating proteins (RIPs) with N-glycosidase
      activity, which depurinate large ribosomal RNA and arrest protein synthesis. RIPs
      so far tested inhibit replication of mRNA as well as DNA viruses and these
      proteins, isolated from plants, are found to be effective against a broad range
      of viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV)
      and herpes simplex virus (HSV). Most of the research work related to RIPs has
      been focused on antiviral activity against HIV; however, the exact mechanism of
      antiviral activity is still not clear. The mechanism of antiviral activity was
      thought to follow inactivation of the host cell ribosome, leading to inhibition
      of viral protein translation and host cell death. Enzymatic activity of RIPs is
      not limited to depurination of the large rRNA, in addition they can depurinate
      viral DNA as well as RNA. Recently, Phase I/II clinical trials have demonstrated
      the potential use of RIPs for treating patients with HIV disease. The aim of this
      review is to focus on various RIPs from plants associated with anti-HIV activity.

PMID- 22160936
TI  - Caspase work model during pathogen infection.
AB  - Caspases are an evolutionarily conserved family of aspartate-specific cystein
      dependent proteases with essential functions in apoptosis and normally exist in
      cells as inactive proenzymes. In addition to the inflammatory caspases, the
      initiator and effector caspases have been shown to have an important role in
      regulating the immune response, but are involved in different ways. We give a
      brief introduction on the benefit of apoptosis on the clearance of invasive
      pathogens, and the caspase functions involved in the immune response. Then we
      construct a working model of caspases during pathogen invasion. A detailed
      description of the three modes is given in the discussion. These three modes are
      regulated by different inhibitors, and there may be a novel way to treat
      intracellular pathogen and autoimmune diseases based on the specific inhibitors.

PMID- 22160937
TI  - Phylogenetic analysis of the non-structural (NS) gene of influenza A viruses
      isolated in Kazakhstan in 2002-2009.
AB  - Although the important role of the non-structural (NS1 and NEP) gene of influenza
      A in virulence of the virus is well established, our knowledge about the extent
      of variation in the NS gene pool of influenza A viruses in their natural
      reservoirs in Kazakhstan is incomplete. 17 influenza A viruses of different
      subtypes were studied in this paper. Seven types of haemagglutinin and five
      different neuraminidase subtypes in eight combinations were found among the
      isolated viruses. A comparison of nucleotide sequences of isolated viruses
      revealed a substantial number of silent mutations, which results in high degree
      of homology in amino acid sequences. By phylogenetic analysis it was shown that
      two distinct gene pools, corresponding to both NS allele A with 5 Clades and B,
      were present at the same time in Kazakhstan. The degree of variation within the
      alleles was very low. In our study allele A viruses had a maximum of 5% amino
      acid divergence in Clade while allele B viruses had only 4% amino acid
      divergence.

PMID- 22160938
TI  - Emerging trends of drug-resistant HIV-1 among drug-treated patients in former
      blood donors in Hubei, China: a three-year surveillance from 2004 to 2006.
AB  - This study aimed to evaluate emerging trends of drug resistance to nucleoside
      reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase
      inhibitors (NNRTIs) among 290 former blood donor HIV-1 infected patients in
      Hubei, China, from 2004 to 2006, all of whom had received anti-HIV-1 therapy. The
      presence of NRTI- and NNRTI-associated mutations were established by sequencing;
      genotypic and predicted phenotypic drug resistance were evaluated using HIVdb
      Program version 5.0.1 (http://hivdb.stanford.edu/pages/algs/HIVdb.html ).
      Genotypic drug resistance analysis showed significant increases in percentages of
      patients carrying HIV-1 strains with M41L, T215Y/F, D67N, K103N, G190A/S, Y181C/F
      or L210W mutations. Of the variants' predicted phenotypic drug resistance, highly
      significant increases were detected in percentages of patients carrying HIV-1
      with high resistance to zidovudine (AZT) or stavudine (D4T) in NRTIs, and to
      delavirdine (DLV), efavirenz (EFV) or nevirapine (NVP) in NNRTIs; intermediate
      resistance to abacavir (ABC), AZT, D4T, didanosine (DDI) or tenofovir disoproxil
      fumarate (TDF) in NRTIs, and to etravirine (ETR) in NNRTIs; and low and potential
      low resistance to lamivudine (3TC), ABC, emtricitabine (FTC) or TDF in NRTIs, and
      to ETR in NNRTIs.

PMID- 22160939
TI  - Molecular characterization of Banana streak virus isolate from Musa Acuminata in
      China.
AB  - Banana streak virus (BSV), a member of genus Badnavirus, is a causal agent of
      banana streak disease throughout the world. The genetic diversity of BSVs from
      different regions of banana plantations has previously been investigated, but
      there are relatively few reports of the genetic characteristic of episomal (non
      integrated) BSV genomes isolated from China. Here, the complete genome, a total
      of 7722bp (GenBank accession number DQ092436), of an isolate of Banana streak
      virus (BSV) on cultivar Cavendish (BSAcYNV) in Yunnan, China was determined. The
      genome organises in the typical manner of badnaviruses. The intergenic region of
      genomic DNA contains a large stem-loop, which may contribute to the ribosome
      shift into the following open reading frames (ORFs). The coding region of BSAcYNV
      consists of three overlapping ORFs, ORF1 with a non-AUG start codon and ORF2
      encoding two small proteins are individually involved in viral movement and ORF3
      encodes a polyprotein. Besides the complete genome, a defective genome lacking
      the whole RNA leader region and a majority of ORF1 and which encompasses 6525bp
      was also isolated and sequenced from this BSV DNA reservoir in infected banana
      plants. Sequence analyses showed that BSAcYNV has closest similarity in terms of
      genome organization and the coding assignments with an BSV isolate from Vietnam
      (BSAcVNV). The corresponding coding regions shared identities of 88% and -95% at
      nucleotide and amino acid levels, respectively. Phylogenetic analysis also
      indicated BSAcYNV shared the closest geographical evolutionary relationship to
      BSAcVNV among sequenced banana streak badnaviruses.

PMID- 22160940
TI  - Bovine herpesvirus 1 protein bICP0 represses the transcription of bISG15 in fetal
      bovine lung cells.
AB  - The ubiquitin-like modifier bISG15 is an antiviral protein found in fetal bovine
      lung (FBL) cells. Bovine Herpesvirus 1(BHV-1), which is a viral pathogen of
      cattle, can infect FBL cells and induce cytopathic effects. Real-time PCR assays
      showed that BHV-1's infection could repress the basal or inducible transcription
      of bISG15 in FBL cells. It demonstrates that this repression effect depends on
      BHV-1 viral infection and new protein synthesis. Our previous work showed that
      bIRF-3 was the key factor in the stimulation of bISG15 in FBL cells, so the
      effect of BHV-1 viral protein on bIRF-3 activating the promoter of bISG15 was
      confirmed. The luciferase assay showed the BHV-1 viral protein bICP0 inhibited
      the activation of bISG15 promoter stimulated by bIRF-3. Taken together, our work
      suggested that BHV-1 had some molecular mechanism to resist the cellular bISG15's
      antiviral functions.

PMID- 22160941
TI  - Surface display of domain III of Japanese encephalitis virus E protein on
      Salmonella typhimurium by using an ice nucleation protein.
AB  - A bacterial cell surface display technique based on an ice nucleation protein has
      been employed for the development of live vaccine against viral infection. Due to
      its ubiquitous ability to invade host cells, Salmonella typhimurium might be a
      good candidate for displaying viral antigens. We demonstrated the surface display
      of domain III of Japanese encephalitis virus E protein and the enhanced green
      fluorescent protein on S. typhimurium BRD509 using the ice nucleation protein.
      The effects of the motif in the ice nucleation protein on the effective display
      of integral protein were also investigated. The results showed that display
      motifs in the protein can target integral foreign protein on the surface of S.
      typhimurium BRD509. Moreover, recombinant strains with surface displayed viral
      proteins retained their invasiveness, suggesting that the recombinant S.
      typhimurium can be used as live vaccine vector for eliciting complete
      immunogenicity. The data may yield better understanding of the mechanism by which
      ice nucleation protein displays foreign proteins in the Salmonella strain.

PMID- 22160942
TI  - Genetic characteristics of 2009 pandemic H1N1 influenza a viruses isolated from
      Mainland China.
AB  - A total of 100 H1N1 flu real-time-PCR positive throat swabs collected from fever
      patients in Zhejiang, Hubei and Guangdong between June and November 2009, were
      provided by local CDC laboratories. After MDCK cell culture, 57 Influenza A
      Pandemic (H1N1) viruses were isolated and submitted for whole genome sequencing.
      A total of 39 HA sequences, 52 NA sequences, 36 PB2 sequences, 31 PB1 sequences,
      40 PA sequences, 48 NP sequences, 51 MP sequences and 36 NS sequences were
      obtained, including 20 whole genome sequences. Sequence comparison revealed they
      shared a high degree of homology (96%-99%) with known epidemic strains
      (A/California/04/2009(H1N1). Phylogenetic analysis showed that although the
      sequences were highly conserved, they clustered into a small number of groups
      with only a few distinct strains. Site analysis revealed three substitutions at
      loop 220 (221-228) of the HA receptor binding site in the 39 HA sequences:
      A/Hubei/86/2009 PKVRDQEG -> PKVRDQEA, A/Zhejiang/08/2009 PKVRDQEG -> PKVRDQER,
      A/Hubei/75/2009 PKVRDQEG -> PKVRDQGG, the A/Hubei/75/2009 was isolated from an
      acute case, while the other two were from patients with mild symptoms. Other key
      sites such as 119, 274, 292 and 294 amino acids of NA protein, 627 of PB2 protein
      were conserved. Meanwhile, all the M2 protein sequences possessed the Ser32Asn
      mutation, suggesting that these viruses were resistant to adamantanes. Comparison
      of these sequences with other H1N1 viruses collected from the NCBI database
      provides insight into H1N1 transmission and circulation patterns.

PMID- 22160943
TI  - The adjectives of inpatient glycemic management.

PMID- 22160944
TI  - Using respondents' uncertainty scores to mitigate hypothetical bias in community
      based health insurance studies.
AB  - Community-based health insurance has been implemented in several developing
      countries to help the poor to gain access to adequate health-care services.
      Assessing what the poor are willing to pay is of paramount importance for
      policymaking. The contingent valuation method, which relies on a hypothetical
      market, is commonly used for this purpose. But the presence of the hypothetical
      bias that is most often inherent in this method tends to bias the estimates
      upward and compromises policymaking. This paper uses respondents' uncertainty
      scores in an attempt to mitigate hypothetical bias in community-based health
      insurance in one rural setting in Cameroon. Uncertainty scores are often employed
      in single dichotomous choice surveys. An originality of the paper is to use such
      an approach in a double-bounded dichotomous choice survey. The results suggest
      that this instrument is effective at decreasing the mean WTP.

PMID- 22160945
TI  - Liminal Masculinity in Richard Selzer's Knife Song Korea.
AB  - The doctor in a foreign country is a recurring theme in physician writer Richard
      Selzer's stories. In his 2009 novel, Knife Song Korea, Selzer returns to this
      theme, examining it in depth through the lens of gender. Selzer features the
      American military surgeon Sloane's multiple border-crossings, namely, from
      America to Korea, from health to patienthood, and from sex-exploitation to love.
      Crossing those visible or invisible borders in the gender and race conscious
      contexts of medical profession and military in wartime Korea, Sloane finds
      himself liminally located among various masculine stereotypes. The mixed-race
      situation in the novel further pushes Sloane to realize the unbearability of the
      baggage of American manhood as represented in his profession. Selzer's punishment
      of Sloane's border-crossings seems to suggest that physicians, together with
      patients, are equally likely to be victimized by the macho norms in medicine. 

PMID- 22160946
TI  - Effect of Chinese drugs for activating blood circulation and detoxifying on
      indices of thrombosis, inflammatory reaction, and tissue damage in a rabbit model
      of toxin-heat and blood stasis syndrome.
AB  - OBJECTIVE: To observe the regulatory effect of Chinese drugs for activating blood
      circulation (ABC) and for activating blood circulation and detoxifying (ABCD) on
      indices of thrombosis, inflammatory reaction, and tissue damage in a rabbit model
      of toxin-heat and blood stasis syndrome. METHODS: Fifty-four rabbits were
      randomized into the normal control group, model group, simvastatin group
      (simvastatin, 0.93 mg/kg per day), ABC group [Xiongshao Capsule, 0.07 g/kg per
      day], and ABCD group [Xiongshao Capsule, 0.07 g/kg per day, and Huanglian
      Capsule, 0.14 g/kg per day]. All except the normal control group received a
      single injection of bovine serum albumin and were fed with high-fat diets for 6
      weeks. At the end of week 4 of giving high-fat diets, a dose of endoxitin was
      given by ear vein injection, and a randomized 2-week treatment was initiated. At
      the end of treatment, blood lipids, circulating endothelial cells, and the
      pathological changes of the aortic arch were assessed. The serum levels of matrix
      metalloproteinases (MMP-9), tissue inhibitors to metalloproteinase (TIMP-1),
      granule membrane protein-140 (GMP-140), plasminogen activator inhibitor-1 (PAI
      1), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor
      necrosis factor-alpha(TNF-alpha) were determined. RESULTS: Compared with the
      model group, ABCD group showed decreased serum triglyceride (TG) level,
      improvement in the pathological change in the aortic arch, and reduction in the
      number of circulating endothelial cells (4.00 +/- 1.41 per 0.9 MUL for ABCD group
      vs 7.83 +/- 1.72 per 0.9 MUL for the model group). In addition, the levels of
      serum GMP-140, PAI-1, and IL-6 in ABCD group were also significantly reduced
      [0.79 +/- 0.20 ng/mL, 5.23 +/- 1.39 ng/mL, 40.64 +/- 10.11 pg/mL for ABCD group
      vs 1.08 +/- 0.31 ng/mL, 7.28 +/- 2.01 ng/mL, 54.44 +/- 13.56 pg/mL for the model
      group, respectively, P < 0.05]. A trend showing improvement in the indices of
      thrombosis, inflammatory reaction, and tissue damage was observed in the ABC
      group when compared to the model group, but the changes were not statistically
      significant (P > 0.05). CONCLUSIONS: Chinese drugs for activating blood
      circulation and detoxifying have beneficial effects on regulating indices of
      thrombosis (GMP-140 and PAI-1) and inflammatory reaction (IL-6) in rabbit model
      with toxic-heat and blood stasis. The effect of the activating blood circulation
      and detoxifying drugs in regulating the levels of serum GMP-140, PAI-1, and IL-6
      was superior to that of the activating blood circulation drugs.

PMID- 22160947
TI  - Analysis of the prognostic factors of very severe aplastic anemia treated with
      Chinese Kidney-invigorating drugs in combination with anti-lymphocyte globulin or
      anti-thymocyte globulin.
AB  - OBJECTIVE: To explore the prognostic factors for very severe aplastic anemia
      (VSAA) patients treated mainly with Chinese Kidney (Shen)-invigorating drugs
      (CKID) combined with anti-lymphocyte globulin (ALG) or anti-thymocyte globulin
      (ATG). METHODS: Twenty-seven VSAA patients were treated with CSID+ALG/ATG therapy
      in conjunction with cyclosporine A, androgen, hemopoietic growth factor, etc. The
      relationship of the effectiveness and some factors (age of patients, course of
      illness, blood and bone marrow figures, etc.) were analyzed. RESULTS: In the 25
      evaluated VSAA patients who had been followed up for over 1 year, 9 patients
      (36.0%) were basically cured, 5 (20.0%) remitted, 6 (24.0%) were markedly
      improved, and 5 (20.0%) were treated in vain, with the total effective rate of
      treatment being 80.0% (20/25). Better clinical therapeutic effects were shown in
      patients newly diagnosed with VSAA, of male sex (P=0.037), >20 years old
      (P=0.045), with an illness course [Symbol: see text] month (P=0.048), with
      peripheral neutrophil count >0.1 * 10(9)/L (P=0.023), and with reticulocyte count
      >10 * 10(9)/L (P=0.002). Platelet count (P=0.620) and bone marrow lymphocyte
      percentage (P=0.736) showed no correlation with the therapeutic effectiveness.
      Multi-factor analysis by the Kaplan-Meier procedure on the factors influencing
      survival showed that rather longer survival times occurred in patients > 20 years
      old, with peripheral neutrophil count [Symbol: see text] 0.1 * 10(9)/L,
      reticulocyte count [Symbol: see text]10 * 10(9)/L, and platelet count > 10 *
      10(9)/L (all P=0.0001). Bone marrow lymphocyte percentage and the initiation time
      of ALG/ATG application (from onset of the illness) showed no significant
      influence on patients' survival time (P=0.085 and P=0.935, respectively).
      CONCLUSIONS: CSKD+ALG/ATG therapy for treatment of VSAA could enhance the current
      clinical therapeutic effects and elevate patients' survival rate. Conditions
      including male sex, age >20 years, illness course [Symbol: see text]1 month,
      neutrophil count >0.1 * 10(9)/L, and reticulocyte count >10 * 10(9)/L are the
      likely effective indices for predicting favorable therapeutic effectiveness in
      newly diagnosed VSAA patients.

PMID- 22160948
TI  - Anticancer effects of 5-fluorouracil combined with warming and relieving cold
      phlegm formula on human breast cancer.
AB  - OBJECTIVE: To investigate the anticancer effects of warming and relieving cold
      phlegm formula (, WRCP), a Chinese medical mixture composed of the aqueous
      extracts of Aconitum carmichaeli, Rhizoma bolbostemmatis, Phytolacca acinosa,
      Panax notoginseng, and Gekko swinhonis Guenther, combined with 5-fluorouracil (5
      FU) on human breast cancer in vivo. METHODS: Seventy-two Nu/Nu mice inoculated
      with MDA-MB-231 breast cancer cells were randomized into the control group, 5-FU
      group, high-dose WRCP (hWRCP) group, medium-dose WRCP (mWRCP) group, low-dose
      WRCP (lWRCP) group, or combination of mWRCP and 5-FU group in a 1:1:1:1:1:1
      ratio. Drug administration was commenced on the day following tumor implantation.
      The control group was injected daily with normal saline (N.S.) intraperitoneally;
      the 5-FU group was injected with 5-FU at 30 mg/kg intraperitoneally every third
      day for a total of 7 treatments; the hWRCP group, mWRCP group and lWRCP group
      received daily doses of 5, 1, and 0.2 g/kg of WRCP, respectively, by gastric
      perfusion; and the combination group was treated with 5-FU plus mWRCP on the same
      schedules as above. All treatments lasted for 22 days. Tumor volume, tumor
      weight, inhibition rate of tumor weight, necrosis rate of tumor, organ index, and
      change in body weight of nude mice were measured. RESULTS: The combination group
      and the hWRCP group had significantly smaller tumor volumes (580+/-339 mm(3) and
      587+/-249 mm(3) versus 1055+/-234 mm(3), respectively), lower tumor weights
      (0.42+/-0.29 g and 0.52+/-0.29 g versus 0.80+/-0.15 g, respectively), and higher
      tumor necrosis rates (22.7% and 25.6% versus 9.4%, respectively) as compared with
      the control group (all <0.05). Similar changes were found in the 5-FU, mWRCP, and
      lWRCP groups when compared with the control group but were not statistically
      significant, except for the tumor weight for the 5-FU group. The combination
      group and the hWRCP group had significantly smaller tumor volumes compared with
      the 5-FU group (778+/-202 mm(3), both <0.05). The combination group had the
      highest tumor inhibition rate (47.7%), followed by the hWRCP group (35.2%) and 5
      FU group (28.3%). The 5-FU group had a lower body weight increase (1.37+/-2.06 g
      versus 5.60+/-0.72 g, <0.05) and a lower spleen index (4.064+/-1.774 mg/10 g
      versus 5.294+/-1.796 mg/10 g) as compared with the control group, whereas the
      combination group reversed the changes in the 5-FU group with the body weight
      increase of 3.52+/-1.80 g (P <0.05) and spleen index of 7.036+/-1.599 mg/10 g (P
      <0.05). The spleen indices in the hWRCP, mWRCP, and IWRCP group were all
      significantly higher than that in the 5-FU group (P <0.01 or P<0.05). No
      significant differences in body weight change were observed in WRCP groups
      compared with the control group P>0.05). CONCLUSION: The treatment combination of
      WRCP and 5-FU was more effective in the inhibition of tumor growth than either
      agent alone and may have potentially additional benefit in improving the general
      condition and immunity of the mice with human breast cancer cell implants.

PMID- 22160949
TI  - Quantitative analysis and simulation of anti-inflammatory effects from the active
      components of Paino Powder () in rats.
AB  - OBJECTIVE: To explore different combinations of the active ingredients of Paino
      Powder ()), including paeoniflorln, naringin, neohesperidln and platyeodin-D,
      which are responsible for the inhibition of carrageenin-induced edema in rats,
      and to evaluate the performance of the orthogonal simulation method in
      quantitative analysis and the simulation of the combinations. METHODS: A 1-level
      (used) and 2-level (unused) orthogonal design was applied to assign 7
      combinations of active components. Aspirin and saline were set as the two
      controls. The carrageen In-Induced edema in the right hind paws of rats was
      established as the acute inflammation model The efficacy indices were expressed
      by the area under the curve (AUC) and the peak value of the swelling change (%)
      over time in rats. RESULTS: Compared with the saline group, the rats in active
      component combinations showed a significant reduction of AUG and peak value in
      the swelling (P<0.05). The maximum anti-inflammatory effect was from the whole
      four-ingredient combination. Among the four ingredients, naringin showed a
      dominant contribution to the combination, while paeoniflorin > platycodin-D >
      naringin contributed in succession. These results are consistent with the results
      of computer simulation. CONCLUSIONS: A single component from Paino Powder does
      not exhibit any anti-inflammatory effect, but some combinations show such effect.
      The strongest inhibition to edema comes from the full 4-ingredient combination.
      The orthogonal simulation method is feasible in the research on decomposed
      formulas of Chinese medicine.

PMID- 22160951
TI  - [Plain abdominal radiograph - is there any additional clinical value based on the
      supine projection?].
AB  - BACKGROUND: To assess the diagnostic value of an additionally acquired plain
      abdominal radiograph in supine position. MATERIALS AND METHODS: Two experienced
      radiologists evaluated retrospectively 2148 consecutive patients having plain
      abdominal radiographs acquired in a tertiary care center. There were 1385
      patients having an erect view and 763 patients with a left lateral decubitus
      view. All patients had a second examination in supine position. First the
      radiographs in erect or decubitus view were evaluated regarding the presence and
      details of pathological changes. After 4 weeks all radiographs including the
      supine view were evaluated again. Next to pathological changes the additional
      value of the supine projection was assessed. The results were compared and the
      additional diagnostic value using the supine view was noted. RESULTS: We
      evaluated 2148 patients having a plain abdominal radiograph (1325 men, 823 women,
      mean 58.9 years, range 15-96 years). The average age within the group acquired
      with left decubitus view was 61.1 years, while patients having an erect view had
      a mean age of 57.0 years. For the first evaluation we found pathological changes
      in 10.5% (decubitus view: 13.1%, erect view 9.5%; p = 0.01). The most frequent
      diagnosis was ileus (7.7%) followed by abdominal free air (2.4%). The results
      were confirmed during the second reading in 99.2%. In 3.5% (decubitus view 5.8%,
      erect view 2.2%) more anatomical structures were depicted considering the supine
      projection and the decubitus/erect projections. The anatomical information was in
      no case relevant for the diagnosis. CONCLUSION: Having the information of an
      supine view additionally to an decubitus/erect view increases the depiction of
      anatomical structures up to 5.8%. Nevertheless there was no additional diagnostic
      relevant information based on the supine view.

PMID- 22160950
TI  - Copper sulfate affects Nile tilapia (Oreochromis niloticus) cardiomyocytes
      structure and contractile function.
AB  - Copper sulfate (CuSO(4))is an inorganic chemical product worldwide used as an
      algaecide and a fungicide in aquaculture and agriculture and being discharged
      into freshwater environments where it can affect the freshwater fauna, especially
      fishes. The impact of copper on fish cardiac function was analyzed in two groups
      of Nile tilapias, Oreochromis niloticus (control group and group exposed to 1 mg
      l(-1) of CuSO(4) for 96 h). Structural and ultra-structural changes were studied
      and related to perturbations of the inotropic and chronotropic responses of
      ventricle strips. Fish of Cu exposed group did not show significant alterations
      in the medium diameter and in the percentage of collagen in the cardiac myocytes
      when evaluated through the light microscope. However, the ultrastructural
      analysis revealed cellular swelling followed by mitochondrial swelling. The
      myofibrils did not show significant variations among groups. Force contraction
      was significantly decreased, and rates of time to tension increase (contraction)
      and decrease (relaxation) were significantly augmented after copper exposure. The
      results suggest that the copper sulfate impairs the oxidative mitochondrial
      function and consequently alters the cardiac performance of this species.

PMID- 22160952
TI  - [70-year-old woman with cardiac hypertrophy and severe pulmonary hypertension:
      pre- or postcapillary?].
AB  - HISTORY AND ADMISSION FINDINGS: A 70-year-old female patient was admitted with
      progressive dyspnea and peripheral edema. The patient had a medical history of
      myocardial hypertrophy, diastolic dysfunction and concomitant pulmonary
      hypertension (PH). INVESTIGATIONS: The physical exam was suggestive of cardiac
      decompensation. Echocardiography showed myocardial hypertrophy, an enlarged left
      atrium as well as enlarged right-sided heart chambers. A prominent tricuspid
      regurgitation jet was present, and the estimated systolic right ventricular
      pressure was 65 mmHg. Invasive hemodynamic measurements showed a marked pressure
      elevation in the pulmonary circulation (mean PAP 51 mmHg), combined with an
      elevated left ventricular end-diastolic pressure (LVEDP) of 30 mmHg and a
      profound increase in the transpulmonary gradient (TPG, 21 mmHg). TREATMENT AND
      COURSE: The synopsis of these findings led to the diagnosis of postcapillary PH
      with a prominent precapillary involvement and cardiac decompensation. Due to
      signs of volume overload, an adequate diuretic therapy was initiated. The patient
      was recompensated and lost 7 kg of weight, which was associated with substantial
      clinical improvement. At invasive follow-up hemodynamic measurement, the
      patient's PAP was substantially decreased and almost reached normal values. The
      previously diagnosed precapillary involvement had disappeared. CONCLUSION: PH is
      a frequent phenomenon in patients with systolic and diastolic heart failure, and
      might initially appear as a combination of pre- and postcapillary involvement.
      The patients' volume status has a major influence on pulmonary hemodynamics. An
      adequate therapy of the underlying heart failure, especially an adequate
      diuresis, may have marked beneficial effects on pulmonary hemodynamics.
      Hemodynamic measurements should always be performed in compensated status.

PMID- 22160953
TI  - [62-year-old woman with breast pain and dizziness after bypass surgery].

PMID- 22160954
TI  - [Right heart catheterization in pulmonary hypertension].

PMID- 22160955
TI  - [A rare differential diagnosis of primary hyperparathyreoidism - case 12/2011].
AB  - HISTORY AND ADMISSION FINDINGS: A 51-year-old woman was admitted from a mental
      institution for evaluation of hypercalcemia. She was treated with lithium for a
      bipolar disorder since 25 years. She complained of polydypsia and polyuria. The
      physical examination findings were unremarkable up to manic symptoms.
      INVESTIGATIONS: Laboratory values showed elevated serum calcium and parathormone.
      Serum phosporus was within the normal range. Neck ultrasound revealed a goiter
      with one nodule in the right thyroid lobe and a suspected enlarged lower left
      parathyroid gland. The sesta-MIBI-scan failed to detect an adenoma. DIAGNOSIS,
      TREATMENT AND COURSE: In light of long-term treatment with lithium and negative
      MIBI-scan, lithium-associated- hyperparathyreoidism (LAH) was suspected. The
      patient refused further preoperative imaging studies, such as c-11 methionine
      positron emission tomography and thyroid scan. Until surgery after stabilization
      of the psychiatric condition, treatment with the calcimimetic cinacalcet was
      initiated. CONCLUSIONS: Long-term lithium therapy is frequently associated with
      LAH. The criteria of diagnosis and therapy are similar to those of primary
      hyperparathyroidism. Lithium alters the set-point of the calcium-sensing-receptor
      and results in elevation of parathormone und hyperplasia of the parathyroid
      glands. Patient with LAH have a higher prevalence of multiglandular disease
      compared with sporadic hyperparathyreoidism. Thus, the preoperative localization
      is challenging. After surgery recurrent or resistant disease is more frequent.
      The calcimimetic cinacalcet is a potential alternative for patients who have
      contraindications to surgery, refuse surgery, or experience recurrent disease
      after surgery.

PMID- 22160956
TI  - [Autonomic dysfunction and cardiac arrhythmia in patients with obstructive  and
      central sleep apnea].
AB  - Obstructive sleep apnea and central sleep apnea with Cheyne-Stokes respiration
      are associated with an increased risk of cardiac arrhythmia. Apnea- associated
      arrhythmia may contribute to sudden cardiac death and premature mortality in
      those patients. Both forms of sleep apnea excert strong modulatory effects on the
      autonomic system with a special autonomic profile. Profound vagal activity is
      leading to bradyarrhythmias, and sypathico-excitation to tachyarrhythmias. Atrial
      fibrillation and ventricular arrhythmias in obstructive and central sleep apnea
      patients are mainly found in combination with cardiovascular comorbidity
      (coronary heart disease, hypertensive heart disease, chronic heart failure).
      Bradyarrhythmias in OSA are induced by a cardioinhibitory vagal reflex due to
      obstructed airway. CPAP-therapy has been demonstrated to reduce arrhythmias.

PMID- 22160990
TI  - The desired moral attitude of the physician: (II) compassion.
AB  - Professional medical ethics demands of health care professionals in addition to
      specific duties and rules of conduct that they embody a responsible and
      trustworthy personality. In the public discussion, different concepts are
      suggested to describe the desired implied attitude of physicians. In a sequel of
      three articles, a set of three of these concepts is presented in an
      interpretation that is meant to characterise the morally emotional part of this
      attitude: "empathy", "compassion" and "care". In the first article of the series,
      "empathy" has been developed as a mainly cognitive and morally neutral capacity
      of understanding. In this article, the emotional and virtuous core of the desired
      professional attitude-compassion-is elaborated. Compassion is distinguished from
      sympathy, empathy and pity. Several problems of compassion as a spontaneous, warm
      emotion for being a professional virtue are discussed: especially questions of
      over-demand, of justice and of concerns because of a possible threat to the
      patient's dignity and autonomy. An interpretation of compassion as processed and
      learned professional attitude, that founds dignity on the general idea of man as
      a sentient being and on solidarity, not on his independence and capacities, is
      developed. It is meant to rule out the possible side effects and to make
      compassion as a professional attitude and as professional virtue attractive,
      teachable and acquirable. In order to reach the adequate warmth and closeness for
      the particular physician-patient-relation, professional compassion has to be
      combined with the capacity of empathy. If appropriate, the combination of both
      empathy and compassion as "empathic compassion" can demand a much warmer attitude
      towards the patient than each of the elements alone, or the simple addition of
      them can provide. The concept of "care" that will be discussed in a forthcoming
      article of this sequel is a missing necessary part to describe the active
      potential of the desired moral attitude of the physician more completely. The
      reconstruction of the desired professional attitude in terms of "empathic
      compassionate care" is certainly not the only possible description, but it is a
      detailed proposal in order to give an impulse for the discussion about the inner
      tacit values and the meaning of medicine and clinical healthcare professions.

PMID- 22160991
TI  - Cornea plana associated with open-angle glaucoma: a case report.
AB  - Cornea plana is a rare disease in which the cornea is flattened with a low
      refractive power. In addition to these features, hypermetropia, deep central
      corneal opacities, hazy corneal limbus, peripheral scleralization of the cornea
      and early arcus senilis can also be seen. Closed-angle glaucoma may occur as a
      result of shallow anterior chamber and narrow angle; however, open-angle glaucoma
      has also been reported in these patients. Measuring the real intraocular pressure
      (IOP) value of such eyes is difficult since tonometers are affected by corneal
      curvature. Therefore, the diagnosis of glaucoma may be delayed for a long time.
      In this case report we aimed to present a case of cornea plana with early open
      angle glaucoma and to investigate which tonometer was appropriate for measuring
      the correct IOP value in such eyes.

PMID- 22160992
TI  - The pathophysiological basis of pharmacological interventions in CAVD.
AB  - Calcific aortic valve disease (CAVD) results in aortic valve stenosis and is one
      of the most common cardiac diseases in both Western and developing countries. The
      burden of this disease is expected to increase rapidly in the future, but there
      are still no relevant pharmacological therapies available and aortic valve
      replacement remains the sole definite therapy. This review presents an overview
      of the most common causes of CAVD, followed by current debates and trials related
      to the onset and progression of this disease. Several differences and
      similarities between the different causes of CAVD are presented. Additionally,
      stages of CAVD are compared with stages in atherosclerosis. Finally, future
      directions for research on CAVD will be discussed.

PMID- 22160993
TI  - Genetics and tailored therapy in cardiovascular disease.

PMID- 22161014
TI  - Molecular cloning, phylogenetic analysis, tissue distribution, and expression of
      the cytokine TWEAK in zebrafish (Danio rerio).

PMID- 22161015
TI  - Clinical and genotypic characteristics of childhood tuberculosis in Chongqing,
      China.
AB  - The aims of this study were to assess the prevalence of isolates of Beijing
      lineage in childhood tuberculosis (TB) and the association between strain family
      and clinical characteristics. A total of 105 children aged less than 18 years
      with culture-confirmed TB were evaluated by spoligotyping and the 12-locus
      mycobacterial interspersed repetitive units-variable number of tandem repeats
      (MIRU-VNTR) scheme. Of 105 isolates spoligotyped, the major spoligotypes found
      were Beijing plus Beijing-like lineages (64.8%), followed by T1 lineages (12.3%)
      and MANU2 lineages (5.7%). MIRU typing identified 72 types that defined 17
      clusters and 55 unique isolates. The largest cluster was 223325173533, which
      belongs to the Beijing lineage. Children in rural areas accounted for 68.8% and
      50.5% of the children with TB were older than 5 years. Extrapulmonary
      tuberculosis accounted for 67.6%, and tuberculous meningitis (TBM) 53.3%. There
      was no association with clinical characterization (P>0.05). In conclusion,
      Beijing isolates are the dominant genotype family in children in China. Beijing
      and non-Beijing strains did not differ in their propensities to cause
      extrapulmonary tuberculosis in general or meningitis in particular and there was
      no significant difference between children infected with Beijing strains and
      those infected with non-Beijing strains with respect to the clinical features.

PMID- 22161016
TI  - "Age is associated with self-reported sleep bruxism, independently of tooth
      loss." A critical commentary.

PMID- 22161017
TI  - Multiple independent evolutionary losses of XY pairing at meiosis in the grey
      voles.
AB  - In many eutherian mammals, X-Y chromosome pairing and recombination is required
      for meiotic progression and correct sex chromosome disjunction. Arvicoline
      rodents present a notable exception to this meiotic rule, with multiple species
      possessing asynaptic sex chromosomes. Most asynaptic vole species belong to the
      genus Microtus sensu lato. However, many of the species both inside and outside
      the genus Microtus display normal X-Y synapsis at meiosis. These observations
      suggest that the synaptic condition was present in the common ancestor of all
      voles, but gaps in current taxonomic sampling across the arvicoline phylogeny
      prevent identification of the lineage(s) along which the asynaptic state arose.
      In this study, we use electron and immunofluorescent microscopy to assess
      heterogametic sex chromosome pairing in 12 additional arvicoline species. Our
      sample includes ten species of the tribe Microtini and two species of the tribe
      Lagurini. This increased breadth of sampling allowed us to identify asynaptic
      species in each major Microtine lineage. Evidently, the ability of the sex
      chromosomes to pair and recombine in male meiosis has been independently lost at
      least three times during the evolution of Microtine rodents. These results
      suggest a lack of evolutionary constraint on X-Y synapsis in Microtini, hinting
      at the presence of alternative molecular mechanisms for sex chromosome
      segregation in this large mammalian tribe.

PMID- 22161018
TI  - The potential role of microRNAs in regulating gonadal sex differentiation in the
      chicken embryo.
AB  - Differential gene expression regulates tissue morphogenesis. The embryonic gonad
      is a good example, where the developmental decision to become an ovary or testis
      is governed by female- or male-specific gene expression. A number of genes have
      now been identified that control gonadal sex differentiation. However, the
      potential role of microRNAs (miRNAs) in ovarian and testicular pathways is
      unknown. In this review, we summarise our current understanding of gonadal
      differentiation and the possible involvement of miRNAs, using the chicken embryo
      as a model system. Chickens and other birds have a ZZ/ZW sex chromosome system,
      in which the female, ZW, is the heterogametic sex, and the male, ZZ, is
      homogametic (opposite to mammals). The Z-linked DMRT1 gene is thought to direct
      testis differentiation during embryonic life via a dosage-based mechanism. The
      conserved SOX9 gene is also likely to play a key role in testis formation. No
      master ovary determinant has yet been defined, but the autosomal FOXL2 and
      Aromatase genes are considered central. No miRNAs have been definitively shown to
      play a role in embryonic gonadal development in chickens or any other vertebrate
      species. Using next generation sequencing, we carried out an expression-based
      screen for miRNAs expressed in embryonic chicken gonads at the time of sexual
      differentiation. A number of miRNAs were identified, including several that
      showed sexually dimorphic expression. We validated a subset of miRNAs by qRT-PCR,
      and prediction algorithms were used to identify potential targets. We discuss the
      possible roles for these miRNAs in gonadal development and how these roles might
      be tested in the avian model.

PMID- 22161019
TI  - Imatinib has the potential to exert its antileukemia effects by down-regulating
      hERG1 K+ channels in chronic myelogenous leukemia.
AB  - Imatinib is a powerful protein tyrosine kinase (PTK) inhibitor that specifically
      targets BCR-ABL, KIT, and PDGFR kinases, has become the current first-line
      therapy for all newly diagnosed chronic myeloid leukemia (CML). Beside PTKs, PTK
      inhibitors alter the activity of a large number of voltage-dependent ion
      channels. hERG1 K(+) channels are highly expressed in leukemia cells and appear
      of exceptional importance in favoring leukemogenesis. The present study explored
      a possible regulatory effect of imatinib upon hERG1 K(+) channels as a means to
      uncover new molecular events involved in the antileukemic activity of this PTK
      inhibitor in CML. The results demonstrated that hERG1 was highly detected in K562
      cells and primary CML cells, and down-regulated by imatinib at mRNA and protein
      levels. Furthermore, imatinib markedly reduced hERG currents in HEK293T-hERG
      cells, this effect was accompanied by inhibition of CML cell proliferation and
      apoptosis, as well as suppression of vascular endothelial growth factor (VEGF)
      secretion. Moreover, these antileukemia effects of imatinib were potentiated by E
      4031, a specific hERG1 inhibitor. Together, these results provide evidence of a
      novel potential molecular mechanism of antileukemic activities by imatinib which,
      independent of targeting tyrosine kinase, highlight hERG1 K(+) channels as a
      therapeutic target for CML treatment.

PMID- 22161020
TI  - Physiological response of Cu and Cu mine tailing remediation of Paulownia
      fortunei (Seem) Hemsl.
AB  - The physiological responses and Cu accumulation of Paulownia fortunei (Seem)
      Hemsl. were studied under 15.7-157 MUmol L(-1) Cu treatments in liquid culture
      for 14 days; the impacts of Cu concentration in the seedlings were evaluated
      under Cu mine tailing culture with acetic acid and EDTA treatment for 60 days.
      Results showed that the concentrations of Chl-a, Chl-b and Carotenoids
      significantly increased (p < 0.05) at 15.7-78.7 MUmol L(-1)Cu treatment and
      significantly decreased at 157 MUmol L(-1) treatment after 14 days of Cu
      exposure. The activities of superoxide dismutase (SOD) and catalase (CAT)
      significantly increased as Cu levels were enhanced and the activities of both SOD
      and CAT under 157 MUmol L(-1) Cu stress were 2.9 and 1.9 times higher than that
      of control, respectively. The concentrations of proline and soluble sugars in the
      leaves of P. fortunei significantly increased as the Cu concentrations were
      elevated. Cu concentrations in roots, stems and leaves of P. fortunei increased
      significantly as Cu levels increased and reached 1911, 101 and 93 MUg g(-1) dry
      weights (DW) at 157 MUmol L(-1) Cu treatment, respectively. The seedlings of P.
      fortunei cultivated in Cu tailing experienced unsuccessful growth and loss of
      leaves in all treatments due to poor nutrition of the Cu tailing. The dry weight
      of P. fortunei increased under all the treatments of acetic acid after 60 days
      exposure. However, dry weight significantly decreased under both levels of EDTA.
      The Cu concentrations increased significantly in roots and decreased in leaves
      when each was treated with both concentrations of acetic acid. The Cu
      concentrations in the roots, stems and leaves increased significantly, and the
      concentrations of Cu in the stems and leaves under the treatment of 2 MUmol L(-1)
      EDTA reached 189.5 and 763.1 MUg g(-1) DW, respectively. The result indicated
      that SOD, CAT, proline and soluble sugars played an important role in coping with
      the oxidative stress of copper. Acetic acid could promote growth and EDTA at the
      experimental levels, which could also enhance Cu absorption and translocation
      into the stems and leaves of P. fortune. Furthermore, acetic acid and EDTA could
      be rationally utilized in Cu-contaminated soil.

PMID- 22161021
TI  - Matrix compliance and RhoA direct the differentiation of mammary progenitor
      cells.
AB  - The regenerative capacity of the mammary gland following post-lactational
      involution depends on the presence of multipotent stem or progenitor cells.
      Mammary progenitor cells exist as a quiescent and self-renewing population
      capable of differentiating into luminal epithelial and myoepithelial cells and
      generating ductal and alveolar structures. The fate choices of these cells are
      regulated by several soluble signals as well as their surrounding extracellular
      matrix. Whereas matrix stiffness has been implicated in organ-specific
      differentiation of embryonic and mesenchymal stem cells, the effects of
      substratum compliance on the more limited fate switches typical of tissue
      specific progenitor cells are unknown. Here, we examined how the mechanical
      properties of the microenvironment affect the differentiation of mammary
      progenitor cells. Immortalized human mammary progenitor cells were cultured on
      synthetic hydrogels of varying stiffness, and their self-renewal and fate
      decisions were quantified. We found that cells cultured on soft substrata
      differentiated preferentially into luminal epithelial cells, whereas those
      cultured on stiff substrata differentiated preferentially into myoepithelial
      cells. Furthermore, pharmacological manipulations of cytoskeletal tension in
      conjunction with analysis of gene expression revealed that mechanical properties
      of the microenvironment signal through the small GTPase RhoA and cytoskeletal
      contractility to modulate the differentiation of mammary progenitor cells. These
      data suggest that subtle variations in the mechanical compliance of a tissue can
      direct the fate decisions of its resident progenitor cells.

PMID- 22161022
TI  - Resistance-associated variants in chronic hepatitis C patients treated with
      protease inhibitors.
AB  - Direct-acting antiviral agents in combination with pegylated interferon (PEG-IFN)
      and ribavirin (RBV) significantly improve sustained virologic response rate and
      reduce duration of therapy among both treatment-naive and treatment-experienced
      patients with genotype 1 chronic hepatitis C. One of the most important
      considerations with both boceprevir and telaprevir is the potential development
      of resistant variants with therapy. Patients with poor intrinsic responsiveness
      to interferon, and those with incomplete virological suppression on protease
      inhibitor therapy, appear to be at higher risk for resistance. In this article we
      will define antiviral resistance and review the data on both in vitro and in vivo
      resistance to protease inhibitors, concentrating on data on boceprevir and
      telaprevir. We will also explore the significance of resistant variants present
      at the baseline, as well as the fate of the resistant variants and the ways to
      minimize the development of resistance to protease inhibitors.

PMID- 22161023
TI  - Management of hepatitis C in patients with chronic kidney disease.
AB  - Chronic kidney disease represents a global health problem. Chronic hepatitis C
      virus (HCV) infection is prevalent in patients with end stage renal disease
      (ESRD) on hemodialysis (HD) and in renal transplant recipients with significant
      impact on morbidity and mortality. Furthermore, HCV can cause various forms of
      glomerulopathy with the predominant type being cryglobulinemia associated
      membranoproliferative glomerulonephritis. Liver enzymes are traditionally used as
      markers of liver injury; however, there is wide variation in aminotransferase
      levels in patients with ESRD. Therefore, diagnosis of chronic hepatitis C (CHC)
      in patients with ESRD is based on HCV antibody testing and further confirmation
      with polymerase chain reaction testing. Current standard therapy for CHC is
      composed of pegylated interferon and ribavirin. However, this combination is
      challenging in patients with ESRD due to its tolerability. We describe in this
      review relevant issues in epidemiology, diagnosis and management of CHC in ESRD,
      HD and renal transplant recipients.

PMID- 22161024
TI  - Amplification of thymosin beta 10 and AKAP13 genes in metastatic and aggressive
      papillary thyroid carcinomas.
AB  - Papillary thyroid carcinoma (PTC) is the most common well-differentiated thyroid
      cancer. Although the great majority of the cases exhibit an indolent clinical
      course, some of them develop local invasion with distant metastasis, and a few
      cases transform into undifferentiated/anaplastic thyroid carcinoma with a rapidly
      lethal course. To identify gene copy number alterations predictive of metastatic
      potential or aggressive transformation, array-based comparative genomic
      hybridization (CGH-array) was performed in 43 PTC cases. Formalin-fixed and
      paraffin-embedded samples from primary tumours of 16 cases without metastasis, 14
      cases with only regional lymph node metastasis, and 13 cases with distant
      metastasis, recurrence or extrathyroid extension were analysed. The CGH-array and
      confirmatory quantitative real-time PCR results identified the deletion of the
      EIF4EBP3 and TRAK2 gene loci, while amplification of thymosin beta 10 (TB10) and
      Tre-2 oncogene regions were observed as general markers for PTC. Although there
      have been several studies implicating TB10 as a specific marker based on gene
      expression data, our study is the first to report on genomic amplification.
      Although no significant difference could be detected between the good and bad
      prognosis cases in the A-kinase anchor protein 13 (AKAP13) gene region, it was
      discriminative markers for metastasis. Amplification in the AKAP13 region was
      demonstrated in 42.9% and 15.4% of the cases with local or with distant
      metastasis, respectively, while no amplification was detected in non-metastatic
      cases. AKAP13 and TB10 regions may represent potential new genomic markers for
      PTC and cancer progression.

PMID- 22161025
TI  - Therapeutic mechanisms of a mindfulness-based treatment for IBS: effects on
      visceral sensitivity, catastrophizing, and affective processing of pain
      sensations.
AB  - Irritable bowel syndrome (IBS) is a prevalent functional disorder characterized
      by abdominal pain and hypervigilance to gastrointestinal sensations. We
      hypothesized that mindfulness training (MT), which promotes nonreactive awareness
      of emotional and sensory experience, may target underlying mechanisms of IBS
      including affective pain processing and catastrophic appraisals of
      gastrointestinal sensations. Seventy five female IBS patients were randomly
      assigned to participate in either 8 weeks of MT or a social support group. A
      theoretically grounded, multivariate path model tested therapeutic mediators of
      the effect of MT on IBS severity and quality of life. Results suggest that MT
      exerts significant therapeutic effects on IBS symptoms by promoting nonreactivity
      to gut-focused anxiety and catastrophic appraisals of the significance of
      abdominal sensations coupled with a refocusing of attention onto interoceptive
      data with less emotional interference. Hence, MT appears to target and ameliorate
      the underlying pathogenic mechanisms of IBS. 

PMID- 22161026
TI  - Autonomy-based arguments against physician-assisted suicide and euthanasia: a
      critique.
AB  - Respect for autonomy is typically considered a key reason for allowing physician
      assisted suicide and euthanasia. However, several recent papers have claimed this
      to be grounded in a misconception of the normative relevance of autonomy. It has
      been argued that autonomy is properly conceived of as a value, and that this
      makes assisted suicide as well as euthanasia wrong, since they destroy the
      autonomy of the patient. This paper evaluates this line of reasoning by
      investigating the conception of valuable autonomy. Starting off from the current
      debate in end-of-life care, two different interpretations of how autonomy is
      valuable is discussed. According to one interpretation, autonomy is a personal
      prudential value, which may provide a reason why euthanasia and assisted suicide
      might be against a patient's best interests. According to a second
      interpretation, inspired by Kantian ethics, being autonomous is unconditionally
      valuable, which may imply a duty to preserve autonomy. We argue that both lines
      of reasoning have limitations when it comes to situations relevant for end-of
      life care. It is concluded that neither way of reasoning can be used to show that
      assisted suicide or euthanasia always is impermissible.

PMID- 22161027
TI  - Autofluorescence and optical coherence tomography findings in optic disc pit
      associated maculopathy: case series.
AB  - The aim of this case series was to report and discuss the clinical, fundus
      autofluorescence (FAF), and optical coherence tomography (OCT) findings of four
      eyes of three cases with optic disc pit (ODP)-related serous macular detachment.
      Three cases were referred to the retina department of our hospital for decreased
      visual acuities in four of their eyes. In addition to ophthalmological
      examinations, OCT and FAF were also performed. ODP-related serous macular
      detachment was detected clinically in all the eyes. OCT also showed two typical
      components named as 'bilaminar structure' in all eyes and OCT and FAF photography
      showed precipitates in the retinal outer layers of the detachment area in three
      eyes. OCT and autofluorescence photography findings can support clinical
      observations in the diagnosis of ODP-related maculopathy.

PMID- 22161073
TI  - Abnormal development of lung innervation in experimental esophageal atresia.
AB  - BACKGROUND/AIM: Patients with esophageal atresia and tracheo-esophageal fistula
      (EA-TEF) have chronic respiratory tract disease and deficient tracheal
      innervation. This study tests the hypothesis in rats with EA-TEF that deficient
      lung innervation could be one of the causes of respiratory disease. MATERIAL AND
      METHODS: Pregnant rats were treated with either 2 mg/kg i.p. adriamycin or
      vehicle on E7, E8 and E9. Lungs and tracheas were retrieved on E15, E18 and E21
      (term: E22). Innervation was examined by regular (PGP 9.5 and GDNF) and whole
      mount (PGP 9.5 and alpha-actin) immunohistochemistry. PGP 9.5 and GDNF mRNA were
      measured by real-time, quantitative RT-PCR and the levels of PGP 9.5 protein by
      immunoblot. Embryonic lung primordia harvested on E13 were cultured for 72 h and
      airway peristalsis was assessed under an inverted microscope. PGP 9.5 expression
      was then examined in explants by whole-mount immunohistochemistry and RT-PCR.
      Values were compared with non-parametric tests. RESULTS: Neural networks were
      present in both EA-TEF and control fetuses on E15, E18 and E21, but the neural
      network was obviously disorganized in whole-mount immunohistochemistry of EA-TEF.
      The pan-neural marker PGP 9.5 protein was increased at term whereas the neural
      chemo-attractant GDNF protein was unchanged. PGP 9.5 mRNA significantly increased
      from subnormal levels on E15 to very increased ones on E18 compared with
      controls. GDNF mRNA levels followed the same trend. Airway peristalsis of
      explanted embryonal lungs was similar in both groups. The neural networks were
      underdeveloped in these primordia, as assessed by whole-mount PGP 9.5
      immunohistochemistry and RT-PCR. CONCLUSIONS: The development of respiratory
      tract innervation in adriamycin-induced EA-TEF was delayed and abnormally
      controlled in rats compared with controls. However, these deficiencies were
      apparently compensated for at term and had no effect on airway peristalsis. The
      possible significance of innervation anomalies for respiratory sequelae in EA-TEF
      patients deserves further investigation.

PMID- 22161074
TI  - The clip and drop back technique in the management of multifocal necrotizing
      enterocolitis: a single centre experience.
AB  - AIM: The surgical management of multifocal necrotizing enterocolitis (NEC)
      remains a major challenge. The "clip-and-drop" strategy with a second-look
      laparotomy permits re-assessment of bowel viability after optimization, thus
      offering the potential of both improving survival and conserving bowel length.
      This study reviews the outcome of this strategy in a single regional center.
      METHODS: Since 2000, NEC patients undergoing emergency laparotomy selectively
      underwent a "clip-and-drop" operation if there was peri-operative instability
      and/or multifocal disease with uncertain bowel viability. Bowel with full
      thickness gangrene was resected and bowel-ends were temporarily tied-off; a
      second-look definitive procedure was performed when the patient had stabilized.
      For this review, in-hospital and follow-up records were studied retrospectively
      for demographics, 30-day mortality and long-term outcome. MAIN RESULTS: Between
      2000 and 2010, 16 patients underwent a "clip-and-drop" operation. The mean post
      conception age was 32.8 weeks (27.7-41.7 weeks) with a median body weight of 1.4
      kg (0.76-4.4 kg) at first operation. Preoperative radiograph showed free gas in
      43.8% and portal venous gas in 37.5% of patients. 2 patients did not survive to
      the second laparotomy. 14 patients received a second laparotomy, after a mean of
      51 h (35-74 h). 2 patients were found to suffer from NEC totalis on the second
      laparotomy and died without further procedures. All other patients (n = 12) had
      stoma formation. 1 patient died 4 days after stoma formation. The 30-day
      mortality for NEC with the "clip-and-drop" strategy was 31.6% (5/16). Among the
      11 survivors, 1 died from liver failure complicated by short bowel syndrome at 5
      months post operation, 2 others died from respiratory complications of
      prematurity despite adequate gastrointestinal function. The median follow-up time
      for the 8 long-term survivors was 45 months (7-129 months). Their median time to
      achieving full feeds was 41 days (range 21-105 days) after the second operation.
      CONCLUSION: The "clip-and-drop" strategy, when used in selected patients with
      multifocal NEC, may help bowel conservation in survivors.

PMID- 22161075
TI  - Liver transplantation in children with cystic fibrosis: experience in our centre
      and preliminary results with a combined en bloc liver-pancreas graft.
AB  - AIM OF THE STUDY: Cystic fibrosis (CF) is a multisystemic disease, with some
      patients developing end-stage liver disease (ESLD), requiring liver
      transplantation (LT). These children usually present with severe mutations of the
      CFTR gene. Almost 100% of patients with severe mutations develop exocrine
      pancreatic insufficiency, leading later to endocrine insufficiency.
      Immunosuppression accelerates the development of insulin-dependent diabetes (IDD)
      in transplanted children with CF. Our aims were: (1) to analyze our experience
      with CF-related ESLD children who received LT, and the relationship to the
      development of IDD; (2) to report our preliminary results with en bloc liver
      pancreas transplantation (CLPT). METHODS: 9 children (6M/3F) with CF and ESLD
      underwent LT between 1993 and 2010; median age and weight were 12.3 years (range:
      5.4-17.0) and 36.7 kg (range: 14.2-58.5), respectively. 4 patients received a
      whole graft, 4 had reduced grafts (1 split) and 1 underwent CLPT.
      Immunosuppression followed the protocols at the time of transplantation. RESULTS:
      Liver function was restored in all patients and none of them needed re
      transplantation. Median follow-up was 105 months (range: 4-206). 1 child died of
      respiratory failure at 23 months after transplantation while awaiting pulmonary
      transplantation. Survival (Kaplan-Meier) at 105 months was 87.5%. 4 children
      already had IDD before transplantation and 3 developed diabetes immediately after
      transplantation. 2 had not developed IDD at the end of the study: the youngest at
      the time of LT (5.4 years, follow-up 7.1 years) and the girl who had had CLPT and
      who recovered normal exocrine and endocrine pancreatic function after
      transplantation. CONCLUSIONS: LT is a realistic option to treat CF-related ESLD
      children. IDD is common in these patients. En bloc liver-pancreas transplantation
      is an appealing option, since it simultaneously restores exocrine function and
      prevents IDD. This procedure has clear technical advantages over simultaneous
      isolated liver and pancreas transplantation.

PMID- 22161076
TI  - Role of growth hormone, glutamine and enteral nutrition in pediatric short bowel
      syndrome: a pilot follow-up study.
AB  - OBJECTIVE: Aim of the study was to evaluate whether growth hormone (GH),
      glutamine (Gln), and enteral nutrition (EN) have a positive effect on intestinal
      adaptation in pediatric patients with short bowel syndrome (SBS). METHOD: 7
      pediatric patients with SBS (small bowel remnant length: 60.57 +/- 15.18 cm; mean
      +/- SEM) were treated with GH (0.05 mg/kg/day), supplemental Gln (0.45 g/kg/day),
      plus EN for 3 weeks. After 3 weeks of treatment, GH was discontinued, and
      patients were maintained on Gln and EN or additionally received a high
      carbohydrate-low-fat diet. Repeat treatment was given at regular intervals.
      Changes in weight and height increase, intestinal absorptive capacity and blood
      indices were evaluated. RESULT: All patients completed the treatment. The
      intestinal absorptive capacity and plasma levels of proteins were significantly
      improved after treatment. There were no major adverse effects in any patient and
      no death occurred. Growth velocity was also well maintained on follow-up. 6
      patients were weaned off PN and lived on HCLF diet supplement with EN, while the
      last patient required less volume of PN. CONCLUSION: Multiple treatment
      approaches with GH, Gln, and EN at an early stage significantly improved
      intestinal adaptation in pediatric patients with SBS. Furthermore, the positive
      effect appeared to be sustained even after GH was discontinued.

PMID- 22161077
TI  - Continuation of vitamin K antagonists as acceptable anticoagulation regimen in
      patients undergoing pulmonary vein isolation.
AB  - BACKGROUND: Recent studies have demonstrated that radiofrequency isolation of the
      pulmonary veins (PVI) is an effective treatment for symptomatic atrial
      fibrillation. Based on these positive results, non- pharmacological therapy has
      been incorporated in the guidelines for drug refractory atrial fibrillation,
      resulting in an increased popularity. The prevention of thromboembolic
      complications remains an important issue. METHODS: In January 2010, we adopted an
      anticoagulation strategy based on continuation of vitamin K antagonists (VKAs)
      and selective use of transoesophageal echocardiogram (TEE). We retrospectively
      analysed the results of this strategy in all patients referred for PVI treatment.
      VKAs were started for all patients 2 months prior to treatment. Discontinuation
      of oral anticoagulation was considered 3 months after treatment based on
      thromboembolic and bleeding risk profile. Bleeding and thromboembolic
      complications were registered during outpatient clinic follow-up up until 3
      months. RESULTS: We performed 151 PVI procedures from January 2010 to March 2011.
      All patients were seen 6 weeks after discharge. No transient ischaemic accidents
      or ischaemic cerebrovascular incidents occurred pre-, peri- or postprocedure.
      Four (2.7%) procedures were complicated by tamponade requiring
      pericardiocentesis. CONCLUSIONS: Our data support the increasing evidence for
      continuation of periprocedural administration of VKAs complemented by a selective
      TEE approach as a safe therapy for thromboembolic complications.

PMID- 22161078
TI  - Interaction between plant polyphenols and the erythrocyte membrane.
AB  - The purpose of these studies was to determine the effect of polyphenols contained
      in extracts from apple, strawberry and blackcurrant on the properties of the
      erythrocyte membrane, treated as a model of the biological membrane. To this end,
      the effect of the substances used on hemolysis, osmotic resistance and shape of
      erythrocytes, and on packing order in the hydrophilic region of the erythrocyte
      membrane was studied. The investigation was performed with spectrophotometric and
      fluorimetric methods, and using the optical microscope. The hemolytic studies
      have shown that the extracts do not induce hemolysis at the concentrations used.
      The results obtained from the spectrophotometric measurements of osmotic
      resistance of erythrocytes showed that the polyphenols contained in the extracts
      cause an increase in the resistance, rendering them less prone to hemolysis in
      hypotonic solutions of sodium chloride. The fluorimetric studies indicate that
      the used substances cause a decrease of packing order in the hydrophilic area of
      membrane lipids. The observations of erythrocyte shapes in a biological optical
      microscope have shown that, as a result of the substances' action, the
      erythrocytes become mostly echinocytes, which means that the polyphenols of the
      extracts localize in the outer lipid monolayer of the erythrocyte membrane. The
      results obtained indicate that, in the concentration range used, the plant
      extracts are incorporated into the hydrophilic area of the membrane, modifying
      its properties.

PMID- 22161080
TI  - Medical malpractice reform: the role of alternative dispute resolution.
AB  - BACKGROUND: Alternative dispute resolution (ADR) refers to techniques used to
      resolve conflicts without going to the courtroom. As healthcare and malpractice
      costs continue to rise, there is growing interest in tactics such as early
      apology, mediation, and arbitration in the medical arena. QUESTIONS/PURPOSES: (1)
      Why is ADR needed? (2) Is ADR useful in health care? (3) What are the current
      legal and political developments favoring ADR? (4) What obstacles remain?
      METHODS: We performed MEDLINE, PubMed, and Google Scholar searches with key words
      "medical malpractice", "ADR", and "alternative dispute resolution" to obtain
      public policy studies, law review articles, case analyses, ADR surveys, and
      healthcare review articles. RESULTS: Early apology and disclosure programs report
      50% to 67% success in avoiding litigation as well as substantial reductions in
      the amount paid per claim. Mediation boasts 75% to 90% success in avoiding
      litigation, cost savings of $50,000 per claim, and 90% satisfaction rates among
      both plaintiffs and defendants. Arbitration is viewed as less satisfying and less
      efficient than mediation but still more time- and cost-effective than litigation.
      The current legal environment is favorable to ADR with recent court decisions
      upholding pretreatment arbitration clauses. The main obstacle to ADR is the
      mandatory reporting requirement of the National Practitioner Data Bank (NPDB).
      CONCLUSIONS: ADR has the potential to help reform the current tort system,
      reducing cost and increasing both parties' satisfaction. Easing the reporting
      requirements for the NPDB would lead to more widespread acceptance of ADR among
      physicians.

PMID- 22161081
TI  - Surgical treatment of Neer Group VI proximal humeral fractures: retrospective
      comparison of PHILOS(r) and hemiarthroplasty.
AB  - BACKGROUND: Neer Group VI proximal humeral fractures often are related to
      persistent disability despite surgical treatment. We retrospectively compared the
      outcome after open reduction and internal fixation with the PHILOS((r)) plate or
      primary hemiarthroplasty in patients with Neer Group VI fractures focusing on
      complications, shoulder function, health-related quality of life (SF-36), and
      potential risk factors for complications. QUESTIONS/PURPOSES: The aim of this
      study was to compare the PHILOS((r)) plate with primary hemiarthroplasty for
      treatment of specific Neer Group VI fractures. We asked whether (1) both
      procedures have comparable clinical and radiologic complication rates; (2) one
      procedure is superior in terms of revision rate; (3) objective and subjective
      shoulder function (Constant-Murley score) and health-related quality of life (SF
      36) were comparable in both groups at final followup; and (4) there are clinical
      or radiologic predictors for complications in any group? METHODS: Between 2002
      and 2007, 44 consecutive patients (mean, 75.2 years) with a Neer Group VI
      proximal humeral fracture were included. Twenty-two patients treated with a
      PHILOS((r)) plate were compared with 22 patients treated by primary
      hemiarthroplasty. Both groups were similar in all criteria. At minimum followup
      of 12 months (mean, 30 months; range, 12-83 months), radiographic control,
      Constant-Murley score, and SF-36 were performed. RESULTS: Fourteen patients with
      complications (63.6%) were counted in the PHILOS((r)) plate group, of which 10
      (45.4%) needed revision surgery, mostly as a result of avascular necrosis and
      screw cut-outs. In the primary hemiarthroplasty group, only one patient needed
      revision surgery (4.5%). Smoking and steroid therapy were substantially
      associated with complications in the PHILOS((r)) plate group. There were no
      differences between the two groups regarding Constant-Murley or SF-36 scores.
      CONCLUSIONS: Angular stable open reduction and internal fixation was associated
      with high complication and revision rates, especially in patients who smoked and
      those receiving steroid therapy. Primary hemiarthroplasty provides limited
      function, which had little influence on the quality of life in this elderly
      collective. There are predictive factors for complications after the treatment of
      Neer Group VI proximal humeral fractures with the PHILOS((r)) plate. Primary
      hemiarthroplasty remains a good option, especially when treating elderly
      patients.

PMID- 22161082
TI  - Does ramosetron reduce postoperative emesis and pain after TKA?
AB  - BACKGROUND: Current pain management protocols involving many anesthetic and
      analgesic drugs reportedly provide adequate analgesia after TKA. However, control
      of emetic events associated with the drugs used in current multimodal pain
      management remains challenging. QUESTIONS/PURPOSES: We determined (1) whether
      ramosetron prophylaxis reduces postoperative emetic events; and (2) whether it
      influences pain levels and opioid consumption in patients managed with a current
      multimodal pain management protocol after TKA. METHODS: We randomized 119
      patients undergoing TKA to receive either ramosetron (experimental group, n = 60)
      or no prophylaxis (control group, n = 59). All patients received regional
      anesthesia, preemptive analgesic medication, continuous femoral nerve block,
      periarticular injection, and fentanyl-based intravenous patient-controlled
      analgesia. We recorded the incidence of emetic events, rescue antiemetic
      requirements, complete response, pain level, and opioid consumption during three
      periods (0-6, 6-24, and 24-48 hours postoperatively). The severity of nausea was
      evaluated using a 0 to 10 VAS. RESULTS: The ramosetron group tended to have a
      lower incidence of nausea with a higher complete response and tended to have less
      severe nausea and fewer rescue antiemetic requirements during the 6- to 24-hour
      period. However, the overall incidences of emetic events, rescue antiemetic
      requirements, and complete response were similar in both groups. We found no
      differences in pain level or opioid consumption between the two groups.
      CONCLUSIONS: Ramosetron reduced postoperative emetic events only during the 6- to
      24-hour postoperative period and did not affect pain relief. More efficient
      measures to reduce emetic events after TKA should be explored. LEVEL OF EVIDENCE:
      Level I, therapeutic study. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 22161083
TI  - Case report: multifocal subchondral stress fractures of the femoral heads and
      tibial condyles in a young military recruit.
AB  - BACKGROUND: Subchondral stress fractures of the femoral head may be either of the
      insufficiency-type with poor quality bone or the fatigue-type with normal quality
      bone but subject to high repetitive stresses. Unlike osteonecrosis, multiple site
      involvement rarely has been reported for subchondral stress fractures. We
      describe a case of multifocal subchondral stress fractures involving femoral
      heads and medial tibial condyles bilaterally within 2 weeks. CASE DESCRIPTION: A
      27-year-old military recruit began having left knee pain after 2 weeks of basic
      training, without any injury. Subsequently, right knee, right hip, and left hip
      pain developed sequentially within 2 weeks. The diagnosis of multifocal
      subchondral stress fracture was confirmed by plain radiographs and MR images.
      Nonoperative treatment of the subchondral stress fractures of both medial tibial
      condyles and the left uncollapsed femoral head resulted in resolution of
      symptoms. The collapsed right femoral head was treated with a fibular strut
      allograft to restore congruity and healed without further collapse. LITERATURE
      REVIEW: There has been one case report in which an insufficiency-type subchondral
      stress fracture of the femoral head and medial femoral condyle occurred within a
      2-year interval. CLINICAL RELEVANCE: Because the incidence of bilateral
      subchondral stress fractures of the femoral head is low and multifocal
      involvement has not been reported, multifocal subchondral stress fractures can be
      confused with multifocal osteonecrosis. Our case shows that subchondral stress
      fractures can occur in multiple sites almost simultaneously.

PMID- 22161084
TI  - Does primary or secondary chondrocalcinosis influence long-term survivorship of
      unicompartmental arthroplasty?
AB  - BACKGROUND: Coexistence of degenerative arthritis and calcium pyrophosphate
      dihydrate (CPPD) crystals (or radiological chondrocalcinosis) with osteoarthritis
      (OA) of the knees is frequent at the time of arthroplasty. Several studies
      suggest more rapid clinical and radiographic progression with CPPD than with OA
      alone. However, it is unclear whether chondrocalcinosis predisposes to higher
      risks of progression of arthritis in other compartments. QUESTION/PURPOSES: We
      questioned whether chondrocalcinosis influences clinical scores, degeneration of
      other compartments, rupture of the ACL, survivorship, reason for revision, or
      timing of failures in case of UKA. METHODS: We retrospectively reviewed 206
      patients (234 knees) who had UKAs between 1990 and 2000. Of these 234 knees, 85
      had chondrocalcinosis at the time of surgery and 63 of the knees subsequently had
      radiographic evidence of chondrocalcinosis observed during followup. We evaluated
      patients with The Knee Society rating system and compared function and
      radiographic progression in the other compartments of patients without and with
      chondrocalcinosis. RESULTS: The use of conventional NSAIDs, radiographic
      progression of OA in the opposite femorotibial compartment of the knee, failure
      of the ACL, and aseptic loosening did not occur more frequently among patients
      with chondrocalcinosis. The 15-year cumulative survival rates were 90% and 87%
      for the knees without and with chondrocalcinosis, respectively, using revision to
      TKA as the end point. CONCLUSION: Our findings show chondrocalcinosis does not
      influence progression and therefore is not a contraindication to UKA.

PMID- 22161085
TI  - Fixation failures of dual mobility cups: a mid-term study of 2601 hip
      replacements.
AB  - BACKGROUND: The use of dual-mobility cups has increased because of a low rate of
      dislocations combined with a 96% 15-year survival rate. However, late cup
      migrations have been attributed to their fixation (tripod - exact fit with two
      pegs and one extraacetabular screw) and the absence of porous coating. In a
      second-generation device, the designs were modified to achieve press-fit fixation
      and a layer of titanium beads was sintered on stainless steel cups.
      QUESTIONS/PURPOSES: We therefore (1) determined the midterm survival of press
      fit, grit-blasted, second-generation cups with or without additional screws,
      compared with original tripod and (2) compared survival of grit-blasted dual
      mobility cups with bimetallic porous-coated cups. METHODS: From a
      multiinstitutional trial, we reviewed 2408 patients with osteoarthritis implanted
      with 2601 prostheses of seven designs of a second-generation dual-mobility cup.
      The criteria for failure were migration, widening radiolucencies in any zone of
      the interface, or revision for cup loosening. The minimum followup was 5 years
      (mean, 7.7 years; range, 5-11 years). RESULTS: The 8-year survival rate of press
      fit, grit-blasted cups was lower than that for press-fit, grit-blasted cups fixed
      with screws (91% versus 100%) and for tripod fixation (98%). The 8-year survival
      rate of press-fit, grit-blasted cups was less than that for press-fit, porous
      coated cups made of the same alloy (91% versus 95%). CONCLUSIONS: The data
      suggested primary fixation of grit-blasted dual-mobility cups should be secured
      with screws. Porous coating sintered on the convex side improved midterm
      survivorship. No deleterious effect of metallosis resulted from sintered titanium
      beads on stainless steel. Long-term followup is required to confirm these
      findings.

PMID- 22161086
TI  - A lipoprotein source of cholesteryl esters is essential for proliferation of CEM
      CCRF lymphoblastic cell line.
AB  - Tumour are characterised by a high content of cholesteryl esters (CEs) stored in
      lipid droplets purported to be due to a high rate of intracellular esterification
      of cholesterol. To verify whether and which pathways involved in CE accumulation
      are essential in tumour proliferation, the effect of CE deprivation, from both
      exogenous and endogenous sources, on CEM-CCRF cells was investigated. Cholesterol
      synthesis, esterification and content, low-density lipoprotein (LDL) binding and
      high-density lipoprotein (HDL)-CE uptake were evaluated in cultured in both
      conventional and delipidated bovine serum with or without oleic or linoleic
      acids, cholesteryl oleate, LDL and HDL. High content of CEs in lipid droplets in
      this cell line was due to esterification of both newly synthesised cholesterol
      and that obtained from hydrolysis of LDL; moreover, a significant amount of CE
      was derived from HDL-CE uptake. Cell proliferation was slightly affected by
      either acute or chronic treatment up to 400 MUM with Sz-58035, an acyl
      cholesteryl cholesterol esterification inhibitor (ACAT); although when the enzyme
      activity was continuously inhibited, CE content in lipid droplets was
      significantly higher than those in control cells. In these cells, analysis of
      intracellular and medium CEs revealed a profile reflecting the characteristics of
      bovine serum, suggesting a plasma origin of CE molecules. Cell proliferation
      arrest in delipidated medium was almost completely prevented in the first 72 h by
      LDL or HDL, although in subsequent cultures with LDL, it manifested an increasing
      mortality rate. This study suggests that high content of CEs in CEM-CCRF is
      mainly derived from plasma lipoproteins and that part of CEs stored in lipid
      droplets are obtained after being taken up from HDL. This route appears to be up
      regulated according to cell requirements and involved in low levels of c-HDL
      during cancer. Moreover, the dependence of tumour cells on a source of
      lipoprotein provides a novel impetus in developing therapeutic strategies for use
      in the treatment of some tumours.

PMID- 22161087
TI  - [Synpolydactyly in a Chinese kindred: mutation detection, prenatal
      ultrasonographic and molecular diagnosis].
AB  - OBJECTIVE: To identify potential mutation responsible for synpolydactyly (SPD) in
      a large Chinese kindred and to offer genetic counseling and prenatal diagnosis
      for the members of the family. METHODS: All family members were examined
      clinically, and blood samples were obtained for linkage analysis and mutation
      screening. Ultrasound examinations were conducted at 16-21 weeks. Amniotic fluid
      sample was obtained by ultrasound-guided amniocentesis at 18 weeks of gestation.
      RESULTS: A large kindred affected with SPD was identified and characterized. With
      two short tandem repeat (STR) markers (D2S1238 and D2S1245) flanking the HOXD13
      gene, the disease was mapped to 2q31. A heterozygous 27 bp expansion within the
      imperfect GCN triplet-repeat of exon 1, c. 184_210dup, was identified. The
      mutation resulted in a gain of 9 alanine residues between the 14th and 15th
      alanine of the normal 15-amino-acid-long polyalanine tract. On ultrasound
      examination, all fingers and toes of the fetus appeared to be normal. Linkage
      analysis and mutation detection confirmed that the fetus did not inherit the
      mutant allele from his affected mother. CONCLUSION: HOXD13 gene mutation was
      responsible for the SPD phenotype in this family. Accurate prenatal diagnosis of
      SPD was achieved with combined ultrasound and molecular analysis.

PMID- 22161088
TI  - [Analysis of survival motor neuron gene conversion in patients with spinal
      muscular atrophy].
AB  - OBJECTIVE: To investigate the type and frequency of gene conversion from SMN1 to
      SMN2 in Chinese patients affected with spinal muscular atrophy (SMA), and to
      explore the relationship between gene conversion and clinical phenotype. METHODS:
      Non-homozygous deletion of SMN1 gene exon 8 was screened among 417 patients with
      SMN1 exon 7 homozygous deletions. To analyze and verify the types of gene
      conversion, genomic DNA sequencing, multiplex ligation-dependent probe
      amplification (MLPA), and gene subcloning and sequencing were carried out.
      RESULTS: Thirty-one patients (7.4% of all) with non-homozygous deletions of SMN1
      exon 8 were detected. Through series of experiments, the fusion genes SMN1/SMN2
      in all cases were delineated. Five types of gene conversions were identified,
      which included SMN2-I7b/SMN1 E8, SMN2-I7a/SMN1 I7b, SMN2-E7/SMN1 I7a, SMN1
      I6/SMN2 E7/SMN1 I7a and SMN2-E7/SMN1 I7a/SMN2 I7b. Such conversions were found in
      the type I-III patients. For 10 patients with type I-III SMA and 3 copies of SMN2
      gene produced by conversion, the average survival age was 5 year and 4 months.
      CONCLUSION: Partial conversions of SMN1 gene have been found among Chinese SMA
      patients. The type of conversion and frequency seem to be different from those of
      other races. Gene conversion to some extent may impact on survival time and rate
      of SMA patients, especially type I SMA.

PMID- 22161089
TI  - [Mutation analysis of keratin 5 and keratin 14 genes in a family with
      epidermolysis bullosa simplex with mottled pigmentation].
AB  - OBJECTIVE: To identify keratin 5 (K5) and keratin 14 (K14) gene mutations in a
      family affected with epidermolysis bullosa simplex with mottled pigmentation.
      METHODS: Genomic DNA was extracted from peripheral blood samples obtained from
      eleven patients from the family and controls. All the exons of K5 and K14 genes
      were amplified using polymerase chain reaction (PCR) and directly sequenced.
      RESULTS: By DNA sequence analysis, a missense mutation in K5 gene (c.237C>T) was
      detected. The same mutation was not found in non-affected members from the family
      and normal controls. CONCLUSION: Mutation in K5 gene (c.237C>T) may be
      responsible for the development of disease in this family.

PMID- 22161090
TI  - [Genetic analysis and prenatal diagnosis for a family with megalencephalic
      leukoencephalopathy and subcortical cysts].
AB  - OBJECTIVE: To identify potential mutation in the MLC1 gene in a Chinese family
      affected with megalencephalic leukoencephalopathy and subcortical cysts (MLC),
      and to provide prenatal diagnosis. METHODS: Genomic DNA of the patients, their
      parents and younger sister were extracted from peripheral blood. That of the
      fetus was extracted from an amniotic fluid sample. A total of 12 exons and at
      least 100 bp flanking the intronic sequence of the MLC1 gene were amplified with
      PCR. MLC1 mutations were screened by sequencing. Linkage analysis was performed
      for the family to assure accuracy of prenatal diagnosis. RESULTS: The two
      patients were both heterozygote for c.177_178delG (p.Ser60AlafsX5) mutation in
      exon 2 and c.598-2A>C change in intron 7. The c.177_178delG mutation was
      inherited from the father, and the c.598-2A>C mutation was inherited from the
      mother. The younger sister and the fetus have both inherited c.177_178delG from
      the father but did not inherit c.598-2A>C from the mother. Prenatal diagnosis
      suggested the fetus to be a carrier for a MLC1 mutation. Linkage analysis was
      consistent with the result of mutation detection. The fetus was born normal as
      predicted. CONCLUSION: The c.598-2A>C is a novel splicing mutation. Prenatal
      diagnosis through DNA sequencing and linkage analysis were performed for the
      first time on Chinese patients with MLC.

PMID- 22161091
TI  - [Expressional changes of neuregulin-1 gene mRNA in peripheral blood from
      schizophrenia patients].
AB  - OBJECTIVE: To explore the effect of anti-psychotic treatment on the expression of
      Neuregulin-1 (NRG1) mRNA in the peripheral blood lymphocytes of schizophrenia
      patients. METHODS: The NRG1 mRNA in peripheral blood lymphocytes was measured
      using semi-quantitative reverse transcription (RT)-PCR in 80 first-onset
      schizophrenia patients, 37 sibling controls and 83 non-related controls. The
      patients were treated with risperdone and quetiapine for 4 weeks. Positive and
      negative symptom scale (PANSS) was used to evaluate the severity and clinical
      efficacy. RESULTS: Prior to the treatment, the expression of NRG1 mRNA expression
      was significantly lower in patients than other two groups (F=73.004, P=0.000).
      From the second week on, the level of NRG1 mRNA expression in patients became
      significantly higher than before and gradually increased, whilst no significant
      difference between sib and non-sib controls. Prior to the treatment, there was
      significant correlation (r=-0.232, P=0.038) between the level of NRG1 mRNA and
      PANSS scores. Four weeks after the treatment, a significant correlation between
      the reduction rate of PANSS and the change of NRG1 mRNA (r=0.27, P=0.016).
      CONCLUSION: The expression of NRG1 gene mRNA is associated with schizophrenia.
      Decreased expression of NRG1 may play a role in the development of schizophrenia,
      which can be improved by anti-psychotic drugs.

PMID- 22161092
TI  - [Molecular genetic study of MECP2 gene for a patient with typical Rett syndrome].
AB  - OBJECTIVE: To provide genetic diagnosis and counseling for a 2-year-old girl with
      typical Rett syndrome through analyzing the methyl-CpG binding protein 2 (MECP2)
      gene. METHODS: Potential mutation of the MECP2 gene was screened by DNA
      sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis
      of members of the family as well as normal controls. Lymphocyte culture for
      karyotype analysis was carried out for the patient to exclude chromosomal
      abnormalities. RESULTS: The karyotype of the girl was normal. No variation of the
      MECP2 gene was detected in the patient by direct sequencing. A heterozygosis
      variation, c.1072G>A in exon 4 of the MECP2 gene was detected in a normal female
      control, which was not found in other controls. The son and daughter of the
      female control were respectively heterozygous and homozygous carriers of the same
      mutation. By MLPA analysis, a heterozygosis deletion of exon 3 and part of exon 4
      was detected in the patient. cDNA amplification and sequencing confirmed the
      presence of a 1176 bp deletion (c.27-1202del1176). The same deletion was not
      detected in the parents. CONCLUSION: A large deletion in MECP2 gene was detected
      with MLPA in a patient featuring typical Rett syndrome. The same deletion was
      missed by sequencing analysis. With cDNA sequencing, the breakage point of the
      mutation can be mapped precisely.

PMID- 22161093
TI  - [ASS1 mutation leading to citrullinemia I in a Chinese Han family].
AB  - OBJECTIVE: To investigate potential mutation of the ASS1 gene in a male infant
      with acute citrullinemia type I. METHODS: Genomic DNA was prepared from
      peripheral blood samples of the family members. Mutation analysis of the 14 ASS1
      exons was carried out by PCR and direct DNA sequencing. RESULTS: A homozygous
      missense mutation of c.970G>A located in exon 13, which results in p.G324S, was
      identified in the child. Sequencing of the parents showed a heterozygous status
      for the same mutation. CONCLUSION: A missense mutation of c.970G>A in the ASS1
      gene is responsible for the pathogenesis of the disease in the infant.

PMID- 22161094
TI  - [Preliminary mapping of an autosomal dominant retinitis pigmentosa gene by
      linkage analysis].
AB  - OBJECTIVE: To map the gene responsible for a three generations family with
      autosomal dominant retinitis pigmentosa (ADRP) and screen the mutation in
      candidate genes. METHODS: For a 14-member family with 7 suspected patients,
      systematic and ophthalmic examinations were performed including visual acuity,
      ophthalmoscopy, perimetry and electrophysiologic test. After the genomic DNA was
      extracted, genome scanning was performed, and candidate genes were screened for
      potential mutations. RESULTS: The maximal two-point LOD score was obtained at
      D1S252 with a value of 2.02 (theta=0.00), and multi-point LOD score reached its
      maximum 2.28 at D1S252. However, no mutations were detected in two candidate
      genes in this region, namely PRPF3 and SEMA4A by direct sequencing. CONCLUSION:
      Significant evidence for linkage was found at the chromosome region of 1p21.1
      q23.3. However, neither PRPF3 nor SEMA4A has harbored a mutation. There may exist
      an additional gene which is responsible for this disease.

PMID- 22161095
TI  - [Analysis of full intronic sequences of HLA-A alleles].
AB  - OBJECTIVE: To analyze the full intronic sequences of human leukocyte antigen
      (HLA)-A alleles in Han Chinese. METHODS: The full-length HLA-A alleles, including
      8 exons and 7 introns, were amplified with a long-template PCR system from 165
      donors from the Chinese Marrow Donor Program (CMDP). The products were cloned
      into a PGEM-T Vector System and sequenced from both directions. Genetic analysis
      was performed using a MEGA4.0 software. All sequences were aligned with a
      ClustalW algorithm. Phylogenetic trees were constructed with a neighbor-joining
      method. Genetic distances were estimated based on p-distance, and a bootstrap
      analysis was applied for assessing the confidence limits of the trees. RESULTS: A
      total of thirty-three full-length sequences of HLA-A alleles, containing 2902
      2918 nucleotides, were derived. A total of 138 point mutations and 9 insertions
      or deletions were found among the 7 introns, which showed remarkable group
      specificity. Intron 1 appeared to be most polymorphic with the highest average GC
      content and evolutionary distances. Eight phylogenetic trees were constructed
      respectively with the derived full-length sequences as well as each of the 7
      introns sequences. Based on full-length sequences, sequences of the HLA-A locus
      were classified into five groups: group I consisted of A*01/03/11/30; group II
      consisted of A*23/24(A9); group III consisted of A*02/68/69(A2/28); group IV
      consisted of A*26/34(A10); and group V consisted of A*29/31/32/33/74(A19). The
      five groups were derived from two ancient lineages, one including groups I and
      II, and another including groups III, IV and V. No substantial difference was
      detected between the trees constructed with the 7 intronic sequences, except that
      group II belonged to different lineages based on introns 2-5 and introns 1 and 7.
      The A*30 variant cluster was close to group I (A*01/03/11/30) and differed from
      group V (A19). CONCLUSION: The full-length sequences of 18 alleles have been
      submitted to GenBank and accepted by the international ImMunoGeneTics database
      (IMGT). Polymorphisms identified within the introns of HLA-A alleles showed
      remarkable group specificity. Such sequences seem to have substantially
      contributed to the recombination of the HLA-A alleles. The A*30 may represent an
      atypical group in which the rates of gene conversion and mutation have been
      unusually high.

PMID- 22161096
TI  - [Association study of a functional SNP rs28493229 of ITPKC gene and Kawasaki
      disease in a Chinese population].
AB  - OBJECTIVE: Kawasaki disease (KD) is a form of acute multi-systemic vasculitis
      with unknown etiology. It is the leading cause of acquired heart disease in
      children due to the frequent occurrence of coronary artery lesions (CALs).
      Recently, a C allele of rs28493229 (G/C) in inositol 1,4,5-trisphosphate 3-kinase
      C (ITPKC) gene was found to significantly increase the risk for KD/CALs in
      Japanese population. It is important to confirm such finding in Chinese
      population to enable prognosis and personalized therapy for KD. METHODS: A case
      control study was performed. The patient group has included 206 unrelated
      patients with KD, and the control group included 285 age, gender and ethnically
      matched children who never had KD. Genotyping of rs28493229 was performed using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      DNA sequencing. The allele, genotype and C allele carrier frequencies were
      compared between the two groups, patients with or without CALs, and patients who
      were resistant or responsive to (intravenous immunoglobulin, IVIG) treatment.
      RESULTS: Frequency of the C allele of rs28493229 was significantly lower in both
      groups than that in the Japanese population (P< 0.01). No significant difference
      was detected between the two groups in terms of allele, genotype and C carrier of
      rs28493229 frequencies. Such frequencies were also similar between patients with
      or without CALs, resistant or responsive to IVIG treatment. CONCLUSION: Our study
      has failed to prove any association between rs28493229 and KD/CALs in Chinese
      patients, which indicated that the C allele of rs28493229 may not be used as a
      molecular marker for determining KD susceptibility, prognosis and effect of
      treatment. The much lower frequency of C allele does not support its significance
      in the occurrence of KD/CALs in Chinese population. It is still necessary to find
      functional SNPs in ITPKC gene which is associated with KD/CALs in Chinese
      population.

PMID- 22161097
TI  - [The research of combining high resolution melting with multiplex ligation
      dependent probe amplification technology in the mutation scanning for PAH gene].
AB  - OBJECTIVE: To explore the value of combining high resolution melting (HRM) with
      multiplex ligation-dependent probe amplification (MLPA) for detecting mutations
      underlying phenylketonuria. METHODS: HRM was used for detecting small mutations
      in phenylalanine hydroxylase gene (PAH) of 26 phenylketonuria patients. The
      results were verified with DNA sequencing. MLPA was used for detecting potential
      deletions/duplications in the PAH gene. Polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) analysis was performed for additional
      potential mutations. RESULTS: A total of 21 mutations were found in 44/52 alleles
      (84.62%), which included a dupEx4. Among the 21 types of mutation, 19 were
      reported previously, and the remaining two were novel mutations: c.584_585insA
      and IVS10+1G>T. In addition, the mutation of R243Q (25%) was the most common type
      in China. CONCLUSION: The study showed that the combination of HRM and MLPA could
      increase the detection rate for mutation in PKU. The study has added new
      information to the human mutation database of PAH and provided a basis for
      clinical diagnosis and prenatal counseling.

PMID- 22161098
TI  - [A case with partial trisomy 7 (q34->qter) derived from a paternal reciprocal
      translocation t(7;14)(q34;q32)].
AB  - OBJECTIVE: To determine the origin of chromosomal aberrants in a mentally
      retarded children, and to correlate the karyotype with phenotype. METHODS:
      Routine G-banding were performed to analyze the karyotype of the patient and her
      parents, and array comparative genomic hybridization (array CGH) were used for
      finely mapping the aberrant regions. RESULTS: The mother had a normal karyotype.
      The father had an apparently balanced translocation involving chromosome 7q and
      14q, the karyotype was 46, XX, t(7;14) (q34;q32), the karyotype of the child was
      then ascertained as 46, XX, der(14) t(7;14) (q34;q32.33) pat. Array CGH finely
      mapped the duplication to 7q34-qter, a 17.09 Mb region, and a very small
      associated deletion of distal chromosome 14 to 14q32.33-qter, a 2.27 Mb region.
      The patient presented some frequently seen features in partial trisomy 7q cases
      such as mental retardation, low birth weight, small nose, cleft palate, low-set
      ears and short neck. CONCLUSION: This result suggested that partial trisomy 7q
      exert mainly phenotypic effect on the patient. Parental karyotype analysis could
      help define the aberrant type.

PMID- 22161099
TI  - [Optimized procedure for fluorescence in situ hybridization in rapid prenatal
      diagnosis of common aneuploidy].
AB  - OBJECTIVE: To optimize the procedure of fluorescence in situ hybridization
      (FISH), and evaluate it in rapid prenatal diagnosis of common aneuploidy.
      METHODS: Amniotic fluid samples from 300 pregnant women were tested by both
      interphase FISH and conventional cell culture for karyotyping from September 2009
      and September 2010. RESULTS: Seven cases of trisomy 21, 4 of trisomy 18, 2 of
      monosomy X, 1 of XXY, 1 of XXX, and 1 of triploidy were detected by FISH in the
      300 amniotic fluid samples. It was concordant with the results from conventional
      karyotype analysis. The concordance rate was 100%. CONCLUSION: Through a
      technical modification of FISH procedure, the detection accuracy and specificity
      was not affected but testing cost reduced greatly. It can be used in rapid
      prenatal diagnosis of common aneuploidy.

PMID- 22161100
TI  - [Impact of five genetic polymorphisms on inter-individual variation in warfarin
      maintenance dose].
AB  - OBJECTIVE: To investigate the effect of genetic polymorphisms in VKORC1, CYP2C9,
      GGCX, EPHX1, APOE genes on inter-individual variation in warfarin maintenance
      dose. METHODS: Two hundred and forty-nine patients with stable warfarin dose were
      enrolled in this study, and the clinical data and blood samples of the patients
      were collected. Genotypes for the 5 genes were determined by using PCR and
      denaturing high performance liquid chromatography (DHPLC) assay. The warfarin
      maintenance doses were compared among patients with different genotypes of the 5
      genes, and a warfarin stable dosing algorithm was derived based on genetic and
      non-genetic factors. RESULTS: Of the 5 genes, VKORC1, CYP2C9 and GGCX were
      associated with warfarin stable dose. The multiple linear regression analysis
      indicated that  VKORC1, CYP2C9 and GGCX genes, age and weight,  had significant
      influence on inter-individual variation in warfarin stable dose, which
      contributed 30.2%, 22.8%, 1.5%, 4.7% and 6.7% respectively. The warfarin stable
      dosing algorithm acquired from the optimal regression model could explain 57.8%
      variation in warfarin dose. CONCLUSION: This study suggested that genetic factors
      are the major determinants of the warfarin maintenance dose, and warfarin stable
      dosing algorithm may be useful for helping clinicians to prescribe warfarin with
      greater safety and efficiency.

PMID- 22161101
TI  - [Analysis of an hereditary coagulation factor XII deficiency in a consanguineous
      pedigree].
AB  - OBJECTIVE: To analyze genetic mutation and explore its molecular pathogenesis for
      an hereditary coagulation factor XII(F XII) deficiency in a pedigree featuring
      consanguineous marriage. METHODS: Activated partial thromboplastin time (APTT), F
      XII procoagulant activity (F XII:C), F XII antigen (F XII:Ag) and other coagulant
      parameters were assayed. For the proband and his family members, exons 1-4,
      introns including the splice junctions of the F XII gene were amplified with
      polymerase chain reaction (PCR). The PCR product was purified and sequenced. The
      mutations were confirmed by sequencing the complimentary strand. RESULTS: The
      proband has featured prolonged APTT at 157.5 s (reference range, 27.0-41.0 s).
      The APTT of his son has increased slightly at 48.3 s. The remaining members of
      the family were in normal range. F XII activity and F XII antigen of the proband
      were significantly decreased (<1%). The F XII activity of his wife, daughter, son
      and mother was also dropped to about 51%, 21%, 21% and 50%, respectively, and so
      was the F XII antigen (42%, 32%, 37% and 48%, respectively). Homozygous missense
      mutation of G->A transition at position 8699 in exon 14 resulting in Gly542Ser
      was identified in the proband. His mother, son and daughter were heterozygous for
      Gly542Ser. In the promoter regions of  F XII gene, the genotype of the proband
      and the other members was 46T/T. CONCLUSION: Homozygous missense mutation
      Gly542Ser was found in a pedigree of hereditary F XII deficiency. The homozygous
      missense mutation might have resulted from his parents by consanguineous
      marriage. Gly542Ser and 46T/T have contributed to the pathogenesis of the
      hereditary factor XII deficiency pedigree.

PMID- 22161102
TI  - [Detection of common deletions and mutations causing alpha-thalassemia in
      Southeast Asians and Southern Chinese with denaturing high performance liquid
      chromatography].
AB  - OBJECTIVE: To establish a comprehensive and simple assay using denaturing high
      performance liquid chromatography (DHPLC) for the diagnosis of most common
      mutations and deletions of alpha-thalassemia gene in Southeast Asians and
      Southern Chinese. METHODS: This assay has included a duplex polymerase chain
      reaction (PCR) followed by DHPLC analysis. An improved PCR was also performed
      followed by DHPLC analysis. With this assay, a blinded study of 160 samples was
      screened for three common mutations and three common deletions. RESULTS: The
      duplex PCR-DHPLC combined with the improved PCR-DHPLC analysis has detected all
      mutations and the wild-type allele. The results were consistent with those by the
      original methods. CONCLUSION: This molecular assay may be used for the diagnosis
      of alpha-thalassemia patients from this geographical region. The method is
      accurate, rapid, semi-automatic and cost-effective, which makes it suitable for
      large-scale screening.

PMID- 22161103
TI  - [Analysis of sex chromosome mosaicisms in early cleavage-stage human embryos and
      blastocysts with poor embryo quality scores].
AB  - OBJECTIVE: To analyze sex chromosome mosaicisms in early cleavage-stage human
      embryos and blastocysts with poor embryo quality score based on the numbers of
      pronucleus(PN) zygotes using X,Y dual color fluorescence in situ hybridization
      (FISH), and to discuss the possible mechanisms. METHODS: Fresh or frozen-thawed
      early cleavage-stage human embryos and blastocysts with poor embryo quality score
      not suitable for embryo transfer were studied with dual color FISH. RESULTS:
      Double signal rate of 2PN among early cleavage-stage embryos was 66.67%, which
      was significantly higher than 1PN and 3PN embryos. Single signal rate of 1PN
      early cleavage-stage embryos was 90.41%, which was significantly higher than 2PN
      and 3PN ones. Three signal rate of 3PN early cleavage-stage embryos was 28.00%,
      which was significantly higher than 1PN and 2PN ones. Double signal rate of 3PN
      ones was 46.00%, which was significantly higher than 1PN ones. The polyploid rate
      of frozen-thawed early cleavage-stage embryos was 23.53%, which was slightly
      higher than that of fresh embryos, but with no statistical significance. The
      mosaicism rate of 24 blastocysts was 100.00% and the double signal dominant (>=
      50%) rate was 62.50%, which was significantly higher than the rate of early
      cleavage-stage embryos. CONCLUSION: Using 2PN as the criterion for embryo quality
      score cannot guarantee the selection of normal fertilized embryo for
      transplantation. Frozen-thawed embryos may harbor more polyploid cells. To avoid
      the selection of embryos with abnormal chromosomes, combinations of pre
      implantation genetic diagnosis (PGD) and prenatal diagnosis are necessary.
      Meanwhile, blastocysts with poor quality scores may provide an important source
      for embryo stem cells.

PMID- 22161104
TI  - [Prenatal diagnosis for two families of congenital factor V deficiency].
AB  - OBJECTIVE: To provide genetic consulting and prenatal diagnosis for two families
      with congenital factor V deficiency based on the known mutations of factor V gene
      (G16088C and G69969T). METHODS: Chorionic DNA was obtained at 12 weeks of
      gestation and analyzed to exclude maternal cell contamination through
      microsatellite DNA analysis. It was then amplified with PCR and sequenced to
      determine the presence of mutations in exons 3 and 23. Factor V activity of the
      blood was assayed at 22 weeks of gestation and 6 months after birth. RESULTS: The
      fetus in case 1 was found to be a heterozygous carrier of the G16088C mutation,
      for whom factor V activity of the cord blood and peripheral blood were 15% and
      53%, respectively. Fetus 2 did not carry the familiar G69969T mutation, for whom
      the factor V activity of cord blood and peripheral blood has measured 32% and
      93%, respectively. Follow-up studies demonstrated that the two infants were both
      in good health without a tendency for bleeding. CONCLUSION: In both cases, the
      genotypes were consistent with the phenotypes. This is the first report of
      prenatal diagnosis of congenital factor V deficiency.

PMID- 22161105
TI  - [Association of ABCG2 gene C421A polymorphism and susceptibility of primary gout
      in Han Chinese males].
AB  - OBJECTIVE: To assess the association between a C421A single nucleotide
      polymorphism (SNP) in exon 5 of ATP-binding cassette, sub-family G (WHITE),
      member 2 (ABCG2) gene and susceptibility of primary gout in Han Chinese males.
      METHODS: For 200 male patients with primary gout and 235 controls, the genotype
      of C421A locus was analyzed by PCR and direct sequencing. Blood glucose, uric
      acid, total cholesterol, triglycerides, creatinine and urea nitrogen was measured
      by an automatic biochemical analyzer. RESULTS: Compared with the controls, there
      was a higher frequency for AA genotype and A allele of the rs2231142 SNP in gout
      patients (22.5% vs. 8.5% by genotype; 44.9% vs. 32.3% by allele). The association
      with gout reached significance (chi-square =15.91, P< 0.001, crude OR=3.02, 95%
      CI:1.36-4.90 and OR (adjusted by age)=1.80, 95% CI: 1.32-2.45 by dominant mode;
      chi-square=6.82, P=0.009, OR=1.67, 95% CI: 1.54-2.27 by recessive mode). Blood
      glucose, uric acid, triglycerides, creatinine and urea nitrogen levels in gout
      patients were significantly higher than those of controls (P< 0.001). CONCLUSION:
      The C421A SNP, in particular AA phenotype, may be associated with susceptibility
      of primary gout in Han Chinese males.

PMID- 22161106
TI  - [Investigation of 1q21 amplification in patients with multiple myeloma using I
      FISH and cIg-FISH].
AB  - OBJECTIVE: To investigate the prevlance of 1q21 amplification in patients with
      multiple myeloma (MM) and its correlation with the progression and prognosis of
      the disease. METHODS: 1q21 amplification was detected in 48 patients with MM
      using cytoplasmic light chain immunofluorescence with fluorescence in situ
      hybridization analysis (cIg-FISH) and interphase fluorescence in situ
      hybridization (I-FISH) analysis combined with CD138 immunomagnetic cell sorting
      (MACS). RESULTS: 1q21 amplification (>= 3 red signals) was detected in
      26/48(54.2%) cases by cIg-FISH and 31/48 (64.6%) cases by I-FISH combined with
      CD138 MACS. There was a good consistency between the two methods (P>0.05). The
      mortality of patients with 1q21 amplification was significantly higher than those
      without (P< 0.05). No significant difference was detected in terms of sex, age,
      Durie-Salmon stage, subgroup and international staging system (ISS) stage between
      patients with 1q21 amplification and those without (P>0.05). CONCLUSION: The
      frequency of 1q21 amplification in MM is high. There was also an association
      between the amplification and poor prognosis. cIg-FISH is consistent with CD138
      MACS combined with I-FISH.

PMID- 22161107
TI  - [Fluorescence in situ hybridization study of acute myeloid leukemia with cryptic
      chromosome rearrangements].
AB  - OBJECTIVE: To detect specific chromosome rearrangements in acute myeloid leukemia
      (AML) using interphase-fluorescence in situ hybridization (FISH). METHODS: All
      cases were studied by R-band karyotypic analysis using direct method and/or short
      term culture for chromosomes preparation. Interphase-FISH was performed in 108
      cases of AML with M5, M4, M2, M3 subtypes including 103 cases with normal
      karyotypes, 4 cases with chromosomal abnormalities other than specific
      chromosomal rearrangements using chromosome translocation probe such as AML1/ETO,
      PML/RARalpha, CBFbeta/MYH11 and MLL. RESULTS: Of 38 cases of M2-AML without
      t(8;21) on conventional cytogenetics(CC) analysis, 4 cases showed positivity for
      AML1/ETO fusion transcript, which included 2 cases with typical signal model and
      2 with insertion. Of 9 cases of M3-AML without t(15;17) on CC analysis, 6 showed
      positivity for PML/RARalpha fusion transcript including 2 with typical signal
      model, 3 with insertion, one without PML/RARalpha rearrangement on reverse
      transcription-PCR and FISH assay using PML/RARalpha probe. FISH assay using the
      RARalpha dual color, break-apart rearrangement probe indicated a partial deletion
      of RARalpha. Of 23 cases with M4 or M4EO-AML without inv(16) on CC analysis, 3
      showed positivity for CBFbeta/MYH11 fusion transcript. Of 38 cases without 11q23
      translocation on CC analysis, all cases were negative for MLL rearrangement.
      CONCLUSION: Interphase-FISH can detect specific chromosome rearrangements such as
      AML1/ETO, PML/RARalpha or CBFbeta/MYH11 in some AML cases with normal karyotype,
      though it seemed less useful for the detection of MLL rearrangement.

PMID- 22161108
TI  - [Mutational analysis for FUT1 gene in two cases with para-Bombay blood type].
AB  - OBJECTIVE: To study two cases of rare para-Bombay blood types Bmh and Amh in
      order to determine clinical strategies of blood transfusion. METHODS: ABO blood
      type was determined with serological assays. The samples were also genotyped with
      polymerase chain reaction-sequence specific primer (PCR-SSP) for potential
      mutations in alpha-1,2-fucosyltransferase gene (FUT1). The results were verified
      with direct sequencing. RESULTS: Two rare para-Bombay blood types, namely Bmh and
      Amh, were identified by serological method, with one being BO1 which contained a
      FUT1 allele 547-548delAG deletion (h1h1), and another being A205O2 which
      contained FUT1 allele a 547-548delAG deletion and a FUT1 allele 658C/T missense
      mutation (h1h3). CONCLUSION: FUT1 allele 547-548delAG deletion and 658C>T
      missense mutation in part form the molecular basis of para-Bombay blood types. As
      Bmh and Amh contain anti-HI in sera, great attention should be paid to avoid
      adverse reaction of blood transfusion in clinics.

PMID- 22161109
TI  - [Clinical application of multiplex ligation-dependent probe amplification for the
      detection exonic copy number alterations in the Dystrophin gene].
AB  - OBJECTIVE: To clarify advantages and disadvantages of using multiplex ligation
      dependent probe amplification (MLPA) for detecting exonic deletions and
      duplications of the Dystrophin gene, and to explore the appropriate management
      for single-exon abnormality detected by MLPA. METHODS: MLPA were performed to
      detect exonic copy number changes in 70 Duchenne/Becker muscular dystrophy
      (DMD/BMD) patients diagnosed by clinical and histological findings. PCR, DNA
      sequencing and real-time PCR were applied to the samples in which MLPA indicated
      single-exon deletion or duplication. RESULTS: Of all 70 patients, MLPA detected
      exonic deletions in 42 (60%), including 12 with single-exon deletion and one with
      ambiguous single-exon deletion. Exon duplications were found in 7 patients (10%),
      among which two were single-exon duplication. 21 patients showed normal results
      (30%). For the 12 patients with single-exon deletion, MLPA results were confirmed
      by PCR in 11. In one patient, a deletion of two nucleotides (c.4470-4471delAA)
      was found by sequencing. A novel two-nucleotide deletion (c.4746-4747delCT) was
      identified in the patient with the ambiguous single-exon deletion. For the two
      patients showed single-exon duplication, MLPA results were confirmed by real-time
      PCR. CONCLUSION: MLPA should be the first choice in detecting Dystrophin gene
      exon deletions and duplications. Single-exon deletion/duplication resulted from
      MLPA should be further evaluated by other methods.

PMID- 22161110
TI  - [Mutation analysis of FGFR3 gene in a family featuring hereditary dwarfism].
AB  - OBJECTIVE: To investigate the clinical symptoms and potential mutation in FGFR3
      gene for a family featuring hereditary dwarfism in order to attain diagnosis and
      provide prenatal diagnosis. METHODS: Five patients and two unaffected relatives
      from the family, in addition with 100 healthy controls, were recruited. Genome
      DNA was extracted. Exons 10 and 13 of the FGFR3 gene were amplified using
      polymerase chain reaction (PCR). PCR products were sequenced in both directions.
      RESULTS: All patients had similar features including short stature, short limbs,
      lumbar hyperlordosis but normal craniofacial features. A heterozygous mutation
      G1620T (N540K) was identified in the cDNA from all patients but not in the
      unaffected relatives and 100 control subjects. A heterozygous G380R mutation was
      excluded. CONCLUSION: The hereditary dwarfism featured by this family has been
      caused by hypochondroplasia (HCH) due to a N540K mutation in the FGFR3 gene.

PMID- 22161111
TI  - [Chromosome 22q11.2 microdeletion and phenotype analysis of patients with non
      syndromic tetralogy of Fallot].
AB  - OBJECTIVE: To investigate the frequency and clinical phenotypes of 22q11.2
      microdeletion in patients with non-syndromic tetralogy of Fallot (TOF). METHODS:
      Six-eight non-syndromic TOF patients (38 males and 30 females, aged 0-11 years)
      were selected and evaluated by history, physical examination and review of
      medical records. After informed consent was obtained, peripheral blood was drawn
      for genomic DNA extraction. Chromosome 22q11.2 microdeletion was screened by
      multiplex ligation-dependent probe amplification (MLPA). Suspected cases were
      confirmed with fluorescence in situ hybridization (FISH). Data was analyzed with
      SPSS 11.5 software. Phenotype-genotype correlations were assessed using Fisher's
      exact test. P values less than 0.05 on a 2-sided test were considered to be
      significant. RESULTS: Six-eight non-syndromic TOF children were screened for a
      22q11.2 deletion, among which 59 (86.8%) presented pulmonary stenosis (PS) and 9
      (13.2%) presented pulmonary atresia (PA). Seven patients (10.3%) were found to
      have carried a deletion. Among these, four had TOF-PS, three had TOF-PA. The
      frequency of 22q11.2 deletion in patients with TOF-PA (3/9, 33.3%) is much higher
      than that of TOF-PS (4/59, 6.80%) (P< 0.05). CONCLUSION: 22q11.2 microdeletion is
      present in approximately 10.3% of patients with non-syndromic TOF. The deletion
      tends to have a higher prevalence in patients with TOF-PA. 22q11.2 deletion
      should be screened in non-syndromic TOF children and genetic counselling may be
      provided.

PMID- 22161112
TI  - [A new human leukocyte antigen class I allele, HLA- B*52:11].
AB  - OBJECTIVE: To identify and confirm a novel HLA allele. METHODS: A new human
      leukocyte antigen class I allele was found during routine HLA genotyping by
      polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) and
      sequencing-based typing (SBT). RESULTS: The novel HLA-B*52 allele was identical
      to B*52:01:01 with an exception of one base substitution at position 583 of exon
      3 where a C was changed to T resulting in codon 195 changed from CAC(H) to
      TAC(Y). CONCLUSION: A new HLA class I allele, B*52:11, is identified, and is
      named officially by the WHO Nomenclature Committee.

PMID- 22161113
TI  - Omental gene expression of adiponectin correlates with degree of insulin
      sensitivity before and after gastric bypass surgery.
AB  - BACKGROUND: Circulating adiponectin is known to correlate negatively with insulin
      resistance in patients with obesity and diabetes. The aim of this study was to
      assess the effect of gastric bypass (GB) surgery on adiponectin gene expression
      in subcutaneous and omental adipose tissues. METHODS: Adipose tissues and plasma
      were obtained from 25 subjects undergoing GB surgery, 15 non-obese subjects, and
      12 subjects after GB surgery. Real-time quantitative reverse transcription
      polymerase chain reaction was used for analysis of the adipose tissues.
      Adiponectin expression was normalized for glyceraldehyde 3-phosphate
      dehydrogenase and expressed as percentage of subject-matched subcutaneous
      expression which was given an arbitrary value of 100%. Insulin resistance was
      assessed by the homeostatic model assessment (HOMA). Circulating adiponectin was
      assayed by ELISA. RESULTS: Omental adiponectin gene expression was fivefold
      higher in subjects after GB when compared with age-matched morbidly obese
      subjects before GB (P < 0.01). There were no statistical differences in omental
      adiponectin gene expression observed in subjects after GB and age-matched non
      obese subjects. For the entire cohort of subjects, there was a significant
      negative correlation between omental adiponectin expression and insulin
      resistance expressed by HOMA values (r = -0.62, P < 0.001). Circulating
      adiponectin was significantly lower (P < 0.05) in the obese group than in the non
      obese and post-GB groups. CONCLUSIONS: Omental adiponectin gene expression
      significantly increases after GB surgery reaching levels equal to age-matched non
      obese subjects. Omental adiponectin expression has a significant negative
      correlation with the insulin resistance status.

PMID- 22161114
TI  - Improvement of nonalcoholic fatty liver disease after bariatric surgery in
      morbidly obese Chinese patients.
AB  - BACKGROUND: Obesity is a risk factor for nonalcoholic fatty liver disease
      (NAFLD), which appears to improve after weight loss induced by bariatric surgery
      in Western countries. The present study aims to determine the alterations of
      clinical measurements and liver histology of NAFLD after bariatric surgery in
      morbidly obese Chinese patients. METHODS: Between November 2006 and December
      2007, 21 morbidly obese patients receiving intra-operative liver biopsy and
      follow-up liver biopsy 1 year after laparoscopic Roux-en-Y gastric bypass were
      enrolled. NAFLD activity score (NAS) and fibrosis stage were histologically
      evaluated. RESULTS: The mean body mass index fell from 43.8 +/- 7.5 to 28.3 +/-
      4.6 kg/m(2) (P < 0.01). Biochemical improvement was found in serum levels of
      alanine aminotransferase (P < 0.01) and gamma-glutamyltransferase (P < 0.01), but
      not aspartate aminotransferase (P = 0.66). Histological improvement was noted in
      NAS (P < 0.01) and individual components, including steatosis (P < 0.01),
      ballooning degeneration (P < 0.01), and lobular inflammation (P = 0.02). Pre
      operatively, 4 (19.0%), 11 (52.4%), and 6 (28.6%) patients were found to have NAS
      >/=5, 3 or 4, and </=2, respectively. All patients had NAS </=2 after surgery.
      Fibrosis stage also showed significant improvement (P < 0.01). CONCLUSIONS:
      Bariatric surgery can achieve a dramatic improvement of NAFLD both biochemically
      and histologically in morbidly obese Chinese patients.

PMID- 22161116
TI  - Application of central composite face-centered design and response surface
      methodology for the optimization of electro-Fenton decolorization of Azure B dye.
AB  - PURPOSE: The aim of this work was to improve the ability of electro-Fenton
      technique for the remediation of wastewater contaminated with synthetic dyes
      using a model azo dye such as Azure B. METHODS: Batch experiments were conducted
      to study the effects of main parameters, such as dye concentration, electrode
      surface area, treatment time, and voltage. In this study, central composite face
      centered experimental design matrix and response surface methodology were applied
      to design the experiments and evaluate the interactive effects of the four
      studied parameters. A total of 30 experimental runs were set, and the kinetic
      data were analyzed using first- and second-order models. RESULTS: The
      experimental data fitted to the empirical second-order model of a suitable degree
      for the maximum decolorization of Azure B by electro-Fenton treatment. ANOVA
      analysis showed high coefficient of determination value (R(2) = 0.9835) and
      reasonable second-order regression prediction. Pareto analysis suggests that the
      variables, time, and voltage produce the largest effect on the decolorization
      rate. CONCLUSION: Optimum conditions suggested by the second-order polynomial
      regression model for attaining maximum decolorization were dye concentration 4.83
      mg/L, electrode surface area 15 cm(2), voltage 14.19 V, and treatment time of
      34.58 min.

PMID- 22161117
TI  - Genotoxic effect of ciprofloxacin during photolytic decomposition monitored by
      the in vitro micronucleus test (MNvit) in HepG2 cells.
AB  - PURPOSE: Ciprofloxacin (CIP), a broad-spectrum, second-generation
      fluoroquinolone, has frequently been found in hospital wastewaters and effluents
      of sewage treatment plants. CIP is scarcely biodegradable, has toxic effects on
      microorganisms and is photosensitive. The aim of this study was to assess the
      genotoxic potential of CIP in human HepG2 liver cells during photolysis. METHODS:
      Photolysis of CIP was performed in aqueous solution by irradiation with an Hg
      lamp, and transformation products were monitored by HPLC-MS/MS and by the
      determination of dissolved organic carbon (DOC). The cytotoxicity and
      genotoxicity of CIP and of the irradiated samples were determined after 24 h of
      exposure using the WST-1 assay and the in vitro micronucleus (MN) test in HepG2
      cells. RESULTS: The concentration of CIP decreased during photolysis, whereas the
      content of DOC remained unchanged. CIP and its transformation products were not
      cytotoxic towards HepG2 cells. A concentration-dependent increase of MN
      frequencies was observed for the parent compound CIP (lowest observed effect
      level, 1.2 MUmol L(-1)). Furthermore, CIP and the irradiated samples were found
      to be genotoxic with a significant increase relative to the parent compound after
      32 min (P < 0.05). A significant reduction of genotoxicity was found after 2 h of
      irradiation (P < 0.05). CONCLUSIONS: Photolytic decomposition of aqueous CIP
      leads to genotoxic transformation products. This proves that irradiated samples
      of CIP are able to exert heritable genotoxic effects on human liver cells in
      vitro. Therefore, photolysis as a technique for wastewater treatment needs to be
      evaluated in detail in further studies, not only for CIP but in general.

PMID- 22161118
TI  - An investigation of anthraquinone dye biodegradation by immobilized Aspergillus
      flavus in fluidized bed bioreactor.
AB  - PURPOSE: Biodegradation and biodecolorization of Drimarene blue K(2)RL
      (anthraquinone) dye by a fungal isolate Aspergillus flavus SA2 was studied in lab
      scale immobilized fluidized bed bioreactor (FBR) system. METHOD: Fungus was
      immobilized on 0.2-mm sand particles. The reactor operation was carried out at
      room temperature and pH 5.0 in continuous flow mode with increasing
      concentrations (50, 100, 150, 200, 300, 500 mg l(-1)) of dye in simulated textile
      effluent on the 1st, 2nd, 5th, 8th, 11th, and 14th days. The reactors were run on
      fill, react, settle, and draw mode, with hydraulic retention time (HRT) of 24-72
      h. Total run time for reactor operation was 17 days. RESULTS: The average overall
      biological oxygen demand (BOD), chemical oxygen demand (COD), and color removal
      in the FBR system were up to 85.57%, 84.70%, and 71.3%, respectively, with 50-mg
      l(-1) initial dye concentration and HRT of 24 h. Reductions in BOD and COD levels
      along with color removal proved that the mechanism of biodecolorization and
      biodegradation occurred simultaneously. HPLC and LC-MS analysis identified
      phthalic acid, benzoic acid, 1, 4-dihydroxyanthraquinone, 2,3-dihydro-9,10
      dihydroxy-1,4-anthracenedione, and catechol as degradation products of Drimarene
      blue K(2)RL dye. Phytotoxicity analysis of bioreactor treatments provided
      evidence for the production of less toxic metabolites in comparison to the parent
      dye. CONCLUSION: The present fluidized bed bioreactor setup with indigenously
      isolated fungal strain in its immobilized form is efficiently able to convert the
      parent toxic dye into less toxic by-products.

PMID- 22161119
TI  - Introducing a knee endoprosthesis model increases risk of early revision surgery.
AB  - BACKGROUND: New equipment and techniques often are used in clinical practice,
      occasionally without evidence of effectiveness and safety. QUESTIONS/PURPOSES: We
      asked whether the stage of introduction of an endoprosthesis model for TKA
      affected the risk of early revision. METHODS: We studied mandatory registry data
      from all centers in Finland (n = 69) that performed TKAs for primary
      osteoarthritis between 1998 and 2004. Of the total of 23,707 patients (28,760
      TKAs), 22,551 patients (27,105 TKAs) had a followup of 5 years; we excluded
      longer followup from the analysis as subsequent revisions might result from wear
      rather than early technical failures. We used proportional hazards modeling for
      calculating the hazard ratios for the first 15 operations and subsequent
      increments of numbers of operations while adjusting for potentially confounding
      variables. RESULTS: For the first 15 operations with a new endoprosthesis, the
      risk was elevated (hazard ratio, 1.48; 95% confidence interval, 1.14-1.91).
      Absolute risk increase of early revision for the first 15 patients was 1.7% (95%
      confidence interval, 0.7-2.7). The risk was not increased as the numbers of TKAs
      incrementally performed increased. CONCLUSIONS: Our data show an increased risk
      of early revision surgery for the first patients obtaining a knee endoprosthesis
      model previously unused in the hospital. Patients should be informed if there is
      a plan to introduce a new model of endoprosthesis in the hospital and offered the
      possibility to choose a conventional endoprosthesis instead. Although introducing
      potentially better endoprostheses is important, there is a need for managed
      introduction of new technology. LEVEL OF EVIDENCE: Level I, prognostic study. See
      the Guidelines for Authors for a complete description of levels of evidence.

PMID- 22161120
TI  - Second-generation annealed highly cross-linked polyethylene exhibits low wear.
AB  - BACKGROUND: Compared with conventional polyethylene, first-generation highly
      cross-linked polyethylenes have low wear, but controversy exists regarding their
      reduced mechanical strength and/or retained free radicals. Second-generation
      highly cross-linked polyethylenes have been developed to reduce wear, maintain
      mechanical strength, and have oxidative resistance, but it is unclear whether
      they do so. QUESTIONS/PURPOSES: The primary objective of this study therefore was
      to determine if a second-generation annealed material has low linear wear at 5
      years followup. Secondary objectives were to evaluate for overall survivorship,
      implant fixation, osteolysis, and effect of socket inclination on wear. METHODS:
      In a multicenter prospective study, we radiographically evaluated 155 patients
      (167 hips) at 3 years, 124 patients (132 hips) at 4 years, and 46 patients (51
      hips) at 5 years. The linear head penetration rate was measured at 6 weeks, 1
      year, and yearly through 5 years. RESULTS: The head penetration per year after
      the first year of bedding-in was 0.024 mm per year at 3 years, 0.020 mm per year
      at 4 years, and 0.008 mm per year at 5 years. The average wear rate over 5 years
      was 0.015 mm per year and represents a 58% improvement over a first-generation
      annealed highly cross-linked polyethylene. The Kaplan-Meier survivorship
      (revision for any reason) was 97.8%. We revised no hip for bearing surface
      failure and observed no osteolysis. Socket inclination did not affect linear
      wear. CONCLUSIONS: These data suggest the linear wear rate for a second
      generation annealed highly cross-linked polyethylene is no greater than that for
      historic controls of first-generation highly cross-linked polyethylenes, and no
      untoward complications were encountered with this new material. LEVEL OF
      EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 22161122
TI  - Combining click-multicomponent reaction: one-pot synthesis of triazolyl methoxy
      phenyl indazolo[2,1-b]phthalazine-trione derivatives.
AB  - [(1,2,3-Triazol-4-yl)methoxy-phenyl]-2H-indazolo[2,1-b]phthalazine-trione
      derivatives were synthesized in a simple and efficient method from the one-pot
      four-component condensation reaction of phthalhydrazide, aromatic propargyloxy
      aldehydes, active methylene compounds (dimedone and 1,3-cyclohexanedione), and
      azides in the presence of Cu(OAc)(2)/sodium ascorbate and p-toluenesulfonic acid
      as catalysts in good to excellent yields.

PMID- 22161121
TI  - Surgical approach to mitral regurgitation in chronic heart failure: when is it an
      option?
AB  - Functional mitral regurgitation (MR) is common in patients with chronic heart
      failure and adversely affects survival and quality of life. Surgery is effective
      in improving symptoms and reverse remodeling of the ventricle. However, its
      effect on survival is unclear. Indications for surgery are challenging given the
      elevated surgical risk of these patients, lack of prospective randomized data,
      and uncertain long-term results in the historical series. A systematic approach
      to functional mitral regurgitation that addresses both the mitral insufficiency
      and the ventricular remodeling with careful patient selection can achieve
      reliable, reproducible, and lasting results. This article reviews the surgical
      procedures to treat functional mitral regurgitation and presents an algorithm for
      their application in patients with congestive heart failure.

PMID- 22161123
TI  - Genomic analysis of phospholipase D family and characterization of GmPLDalphas in
      soybean (Glycine max).
AB  - Phospholipase D (PLD) and its product phosphatidic acid play important roles in
      the regulation of plant growth, development, and stress responses. The genome
      database analysis has revealed PLD family in Arabidopsis, rice, poplar and grape.
      In this study, we report a genomic analysis of 18 putative soybean (Glycine max)
      PLD genes (GmPLDs), which exist in the 14 of 20 chromosomes. GmPLDs were grouped
      into six types, alpha(3), beta(4), gamma, delta(5), epsilon(2), and zeta(3),
      based on gene architectures, protein domains, evolutionary relationship, and
      sequence identity. These GmPLDs contained two HKD domains, PX/PH domains (for
      GmPLDzetas), and C2 domain (for the other GmPLDs). The expression patterns
      analyzed by quantitative reverse transcription PCR demonstrated that GmPLDs were
      expressed differentially in various tissues. GmPLDalpha1, alpha2, and beta2 were
      highly expressed in most tissues, whereas GmPLDdelta5 was only expressed in
      flowers and GmPLDzeta1 was predominantly expressed in flowers and early pods. The
      expression of GmPLDalpha1 and alpha2 was increased and that of GmPLDgamma was
      decreased by salt stress. GmPLDalpha1 protein expressed in E. coli was active
      under the reaction conditions for both PLDalpha and PLDdelta, hydrolyzing the
      common membrane phospholipids phosphatidylcholine, phosphatidylethanolamine, and
      phosphatidylglycerol. The genomic analysis for soybean PLD family provides
      valuable data for further identity and characterization of their functions.

PMID- 22161124
TI  - SRY protein function in sex determination: thinking outside the box.
AB  - Even though the mammalian sex-determining gene Sry has been intensively studied
      for the two decades since its discovery, the regions outside the conserved HMG
      box DNA-binding domain have received less attention due to a lack of sequence
      conservation and of obvious structural/functional motifs. Here, we summarize the
      available evidence for function beyond the HMG box, identify the known and
      postulated biochemical functions of the non-HMG-box domains in sex determination,
      and present possible explanations for the puzzling diversity of these non-HMG-box
      domains.

PMID- 22161125
TI  - A role for estrogen in somatic cell fate of the mammalian gonad.
AB  - Estrogen is both necessary and sufficient to drive ovarian development in many
      nonmammalian vertebrates. However, the role of estrogen in the mammalian gonad is
      less clear. Mouse ovarian development can proceed in the absence of estrogen
      signaling, but granulosa cell fate cannot be maintained. Estrogen receptor
      expression is conserved in the indifferent gonad of all mammals and many species
      also express the CYP19 gene that encodes aromatase, in the early ovary.
      Furthermore, estrogen is sufficient to drive ovarian development of the
      indifferent gonad in marsupial mammals. Here we review the function of estrogen
      in the mammalian gonad and propose a model for its action in establishing and
      maintaining ovarian somatic cell fate.

PMID- 22161127
TI  - Monitoring cardiac fibrosis: a technical challenge.
AB  - The heart contains a collagen network that contributes to the contractility of
      the heart and provides cardiac strength. In cardiac diseases, an increase in
      collagen deposition is often observed. This fibrosis formation causes systolic
      and diastolic dysfunction, and plays a major role in the arrythmogenic substrate.
      Therefore, accurate detection of cardiac fibrosis and its progression is of
      clinical importance with regard to diagnostics and therapy for patients with
      cardiac disease. To evaluate cardiac collagen deposition, both invasive and non
      invasive techniques are used. In this review the different techniques that are
      currently used in clinical and experimental setting are summarised, and the
      advantages and disadvantages of these techniques are discussed.

PMID- 22161126
TI  - Measuring the avoidance behaviour shown by the snail Hydrobia ulvae exposed to
      sediment with a known contamination gradient.
AB  - This study tested the hypothesis that the snail Hydrobia ulvae will recognise
      differences in the contamination levels of sediment and avoid the more
      contaminated zones. Instead of testing avoidance behaviour in a two-compartment
      system, a linear contamination gradient has been devised in which several zones
      containing sediment with different contamination levels could be "chosen". A
      sediment of known severe contamination was collected and mixed with a non-toxic
      sediment to comprise a linear gradient with four concentrations of 0, 30, 60 and
      100% contamination. Thus, the individuals were free to move between fields of
      different concentration (unforced conditions). During 24 h of exposure, the
      distribution of the organisms on fields was recorded and organisms' percentage
      that avoided each field was calculated for each concentration. At 30 and 60% of
      contamination, avoidance was around 50% for all periods of exposure. Avoidance at
      100% contamination ranged between 11 and 56% (rates lower than expected).
      Organisms that did not avoid the 100% contamination revealed that they were
      inactive, indicating either that non-mobility and retraction within their shell
      may be alternative defence strategies, or else the high contamination may have
      impaired their ability to escape. The percentage of preference shown to the
      uncontaminated sediment ranged between 64 and 74%. The initial hypothesis was
      supported: H. ulvae avoids the more contaminated sediment. The assay proposed has
      been shown to be simple, rapid and effective; in addition, it is considered
      ecologically useful since the effects resulting from the avoidance are similar to
      the extinction of the population.

PMID- 22161130
TI  - Progranulin overexpression predicts overall survival in patients with
      glioblastoma.
AB  - Despite multimodal treatment, patients with astrocytoma still face a poor
      survival, and identification of valuable prognostic factors is crucial to yield
      effective individual therapy strategies. The aim of this study was to investigate
      progranulin (PGRN) expression in astrocytomas and explore its association with
      tumor grade and overall patient survival by scoring the PGRN immunoreactivity of
      both tumor cells and blood vessels. About 210 astrocytoma samples with different
      WHO grades and 14 normal brain tissues were studied by immunohistochemistry for
      PGRN. Semi-quantitative RT-PCR and Western blot were carried out to confirm its
      expression in 35 tumor specimens. Serum levels of PGRN in glioblastoma were
      examined by enzyme immunometric assay. PGRN expression was almost undetectable in
      the normal brain tissues by immunohistochemistry but increased in both
      astrocytoma cells and tumor blood vessels with pathological grading. Sera in
      glioblastoma were significantly higher than in healthy control. In grade II
      astrocytoma, strong vascular PGRN expression was closely related to tumor
      recurrence. In glioblastoma, high total PGRN expression, strong vascular PGRN
      expression, and strong tumor cellular PGRN expression all correlated with
      decreased patient survival in univariate analysis. However, only total PGRN
      expression as well as vascular PGRN expression status was independently
      associated with patient's survival in the multivariate analysis. These results
      suggest that PGRN, involved in astrocytoma progression, may serve as a prognostic
      biomarker for glioblastoma.

PMID- 22161131
TI  - Atypical eye lesion in a human immunodeficiency virus-positive patient.
AB  - AIDS-related Kaposi sarcoma (KS), nowadays known to be an angioproliferative
      disease, occurs in several clinical-epidemiological forms, all of which are
      associated with infection by human herpesvirus-8. KS can affect the eye, with the
      bulbar conjunctiva and lacrimal gland being rare sites of occurrence. We present
      a case of AIDS-related KS of the conjunctiva and also discuss recent literature.

PMID- 22161132
TI  - Histological study of graft failure in AlphaCor transplantation.
AB  - To report clinical and histopathologic findings in a case of a failed AlphaCor
      artificial cornea explanted due to corneal stromal melting. We describe the case
      of a 77-year-old man who received multiple penetrating keratoplasties (PKPs) and
      subsequent placement of an AlphaCor artificial cornea. Examination showed total
      corneal infiltration as well as an AlphaCor that was partially dehisced from the
      host cornea. After explantation, the implant and adjacent host tissue underwent
      hematoxylin and eosin staining and high-resolution scanning electron microscopy
      (HR-SEM). Histopathologic analysis of the specimens revealed infiltration of the
      skirt pores by reactive corneal fibroblasts. Although the AlphaCor implant is an
      established method of treating multiple failed PKPs, in this case, HR-SEM imaging
      strongly suggests that the strength of the interface between the implant and
      corneal tissue is highly dependent on collagen deposition between the pores found
      in the implant skirt. Collagen deposition then increases the mechanical strength
      of the cornea-skirt interface.

PMID- 22161133
TI  - Interweaving microRNAs and proinflammatory cytokines in gastric mucosa with
      reference to H. pylori infection.
AB  - Using endoscopic biopsies, gastric mucosal expression levels of interleukin (IL)
      1beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) messenger RNA
      (mRNA) and microRNAs (miRNAs) that were differentially expressed in association
      with Helicobacter pylori were assessed by quantitative reverse-transcriptase
      polymerase chain reaction. Among the H. pylori-positive mucosa, 17 out of 29
      miRNAs had significant correlations with at least one of the four proinflammatory
      cytokines in expression. Among the 17 miRNAs, 15 were associated with the degree
      of neutrophil infiltration and, more prominently, the degree of mononuclear cell
      infiltration, according to the updated Sydney system. Persistent H. pylori
      infection may affect the mucosal expression profiles of miRNAs via chronic
      inflammation mediated by proinflammatory cytokines. There were significant
      positive correlations between certain miRNAs including the microRNA-200 family
      and IL-1beta, IL-6, or TNF-alpha mRNA in H. pylori-negative gastric mucosa.
      Underscoring the causal association between miRNAs and proinflammatory cytokines
      may provide insights into the pathogenesis of H. pylori-associated gastritis
      linking to gastric carcinogenesis.

PMID- 22161134
TI  - Subacute toxicity assessment of water disinfection byproducts on zebrafish.
AB  - Disinfection of raw water is essential to the production of drinking water.
      However, by-products of disinfection may exert toxic effects. The potential toxic
      effects of two of these compounds, 4-ethylbenzaldehyde (EBA) and 2,4
      difluoroaniline (DFA) were investigated using the zebrafish (Danio rerio) model.
      The two compounds, dissolved, were introduced in duplicate aquariums containing
      zebrafish in two different concentrations based on LC50 values. The aquarium
      water containing EBA or DFA was changed every 96 h throughout the 3 months of
      treatment. Behavior of the fish in each replicate was inspected twice daily. In
      course of treatment with both concentrations, fish exposed to DFA displayed
      behavior associated with visible anxiety, while EBA treated were lethargic and
      did not evade capture. Application of both concentrations of each component into
      the aquarium water resulted in dystrophic lesions in the liver, kidney and skin
      of the fish while preneoplastic lesions and tumors were not observed.

PMID- 22161135
TI  - Retrieval of proximally migrated plastic biliary stents using a     metal stent.

PMID- 22161136
TI  - Use of Foley's catheter to control port-site bleeding in bariatric surgery.
AB  - Abdominal wall bleeding in the port-site insertion placed during laparoscopic
      bariatric surgery is often difficult to control. From January 2005 to August
      2011, 226 patients underwent bariatric surgery at our institutions. Seventeen
      patients (7.5%) presented port-site bleeding that could not be controlled with
      electrocautery and Foley's catheter (24 F) was used for bleeding inhibition. Of
      the 17 patients, there were 12 females (70.6%) and five males (29.4%) with a mean
      age of 38.35 years. Mean body mass index (BMI) was 44.2. Most of bleeding port
      sites were located in hypochondrium and were 12-mm size. After the catheter
      removal (median 36 h), bleeding did not recur in any case. There were no other
      complications related to the port-side bleeding and the Foley catheter placement.
      Hospital stay was not prolonged due to the use of the Foley catheter. Port-site
      bleeding in bariatric surgery is a frequent complication. In up to 7.5% of the
      cases, the haemorrhage cannot be controlled with electrocautery. Compression with
      Foley catheter balloon is a safe and efficient method to stop bleeding.

PMID- 22161137
TI  - Programmed cell death 6 (PDCD6) as a prognostic marker for gastric cancers.
AB  - Programmed cell death 6 (PDCD6) plays an important role in apoptotic cell death
      and tumorigenesis. In this study, we investigated whether PDCD6 contributes to
      the development and/or progression of gastric cancers. PDCD6 protein expression
      was examined in 169 advanced gastric cancer specimens by immunohistochemistry and
      then correlated with clinicopathologic parameters. We also analyzed mutations,
      methylation status, and alterations in DNA copy number and mRNA transcripts, and
      protein expression of PDCD6 in gastric cancers. The effect of PDCD6 on cell
      viability and death was further examined in wild- and mutant-type PDCD6
      transfected AGS and HEK293T cell lines. Increased expression of PDCD6 expression
      was detected in 124 (73.4%) out of 169 gastric cancer specimens. Statistically,
      altered expression of PDCD6 was closely associated with survival rates (P =
      0.0069). One non-sense mutation was found at codon 175 of PDCD6, and no
      hypermethylation was found in gastric cancers. Decreased copy numbers and mRNA
      expression of PDCD6 were found in 7 (16.7%) and 10 (23.8%) of 42 gastric cancer
      specimens, respectively. AGS and HEK293T cells transfected with wild-type PDCD6
      showed marked inhibition of cell viability and induction of cell death via
      activation of mitochondrial cell death pathways, whereas mutant-type PDCD6 showed
      partial ablation of tumor suppressor activity. In addition, AGS cells transfected
      with wild-type PDCD6 and treated with 5-FU showed synergistic inhibition of cell
      viability (P < 0.001). These data provide evidence that the PDCD6 gene is a
      significant prognostic biomarker for advanced gastric cancer patients.

PMID- 22161138
TI  - System review and metaanalysis of the relationships between five metabolic gene
      polymorphisms and colorectal adenoma risk.
AB  - The relationships between some metabolic (including EPHX1, GSTs and NQO1) gene
      polymorphisms and colorectal adenoma (CRA) risk have been commonly studied, and
      no conclusions are available up to now. Therefore, we quantitatively studied the
      relationships by a metaanalysis. The databases of Medline and Embase were
      retrieved updated to June 15th, 2011. Crude or adjusted odds ratio (crude OR or
      adjusted OR) and 95% confidence interval (95%CI) were calculated to present the
      strength of the associations. Overall, nine case-control studies for EPHX1
      Tyr113His and His139Arg, five case-control studies for GSTM1, four studies for
      GSTP1 Ile105Val, two studies for GSTP1 Ala114Val, six studies for GSTT1 and four
      studies for NQO1 Pro187Ser were included in this metaanalysis. The results of
      combined analyses indicated that EPHX1 Tyr113His and His139Arg, GSTT1, GSTM1,
      GSTP1 Ile105Val and Ala114Val were not associated with CRA risk [crude OR
      (95%CI): 0.98 (0.90-1.07) and P ( z-test) = 0.65 for EPHX1 His carriers vs.
      Tyr/Tyr; 1.05 (0.97-1.15) and P ( z-test) = 0.21 for EPHX1 Arg carriers vs.
      His/His; 1.05 (0.92-1.20) and P ( z-test) = 0.47 for GSTT1 Null vs. Present; 1.01
      (0.90-1.13) and P ( z-test) = 0.90 for GSTM1 Null vs. Present; 1.04 (0.92-1.17)
      and P ( z-test) = 0.56 for G carriers vs. AA for GSTP1 Ile105Val; 0.88 (0.70
      1.11) and P ( z-test) = 0.28 for T carriers vs. CC for GSTP1 Ala114Val]. In
      contrast, Ser allele of NQO1 Ser187Pro might be a modest risk factor for CRA
      development [1.19 (1.06-1.33) and P ( z-test) = 0.003 for Ser carriers vs.
      Pro/Pro]. To get more precise evidences, adjusted ORs (95%CI) for EPHX1
      Tyr113His, His139Arg, GSTP1 Ile105Val and NQO1 Ser187Pro were also calculated
      based on adjusted ORs (95%CIs) reported in primary studies. The results still
      indicated that EPHX1 Tyr113His, His139Arg and GSTP1 Ile105Val were not associated
      with CRA risk except for NQO1 Ser187Pro. When subgroup analyses were performed
      for population-based case-control studies or studies in HWE for EPHX1 Tyr113His
      and His139Arg, and NQO1 Ser187Pro polymorphisms, the results were persistent.
      Although with modest limitations and biases, this metaanalysis suggests that
      EPHX1 Tyr113His and His139Arg, GSTT1, GSTM1, GSTP1 Ile105Val and Ala114Val
      polymorphisms may be not risk factors for CRA development, while Ser allele of
      NQO1 Ser187 Pro may be a modest risk factor for CRA development, and may be used
      with other genetic markers for screening CRA in the future.

PMID- 22161140
TI  - Purification and biochemical characterization of a highly thermostable xylanase
      from Actinomadura sp. strain Cpt20 isolated from poultry compost.
AB  - An extracellular thermostable xylanase from a newly isolated thermophilic
      Actinomadura sp. strain Cpt20 was purified and characterized. Based on matrix
      assisted laser desorption-ionization time-of-flight mass spectrometry analysis,
      the purified enzyme is a monomer with a molecular mass of 20,110.13 Da. The 19
      residue N-terminal sequence of the enzyme showed 84% homology with those of
      actinomycete endoxylanases. The optimum pH and temperature values for xylanase
      activity were pH 10 and 80  degrees C, respectively. This xylanase was stable
      within a pH range of 5-10 and up to a temperature of 90  degrees C. It showed
      high thermostability at 60  degrees C for 5 days and half-life times at 90 
      degrees C and 100  degrees C were 2 and 1 h, respectively. The xylanase was
      specific for xylans, showing higher specific activity on soluble oat-spelt xylan
      followed by beechwood xylan. This enzyme obeyed the Michaelis-Menten kinetics,
      with the K (m) and k (cat) values being 1.55 mg soluble oat-spelt xylan/ml and
      388 min(-1), respectively. While the xylanase from Actinomadura sp. Cpt20 was
      activated by Mn(2+), Ca(2+), and Cu(2+), it was, strongly inhibited by Hg(2+),
      Zn(2+), and Ba(2+). These properties make this enzyme a potential candidate for
      future use in biotechnological applications particularly in the pulp and paper
      industry.

PMID- 22161141
TI  - Identification and molecular characterization of a novel DyP-type peroxidase from
      Pseudomonas aeruginosa PKE117.
AB  - A new DyP-type peroxidase from Pseudomonas aeruginosa PKE117 was identified and
      characterized. The dypPa was first identified via sequence analysis and then
      cloned in Escherichia coli. Subsequently, the recombinant protein DyPPa was
      expressed and purified. Its DNA sequence analysis revealed an open reading frame
      of 897 bp, encoding a protein monomer of 299 amino acid residues with isoelectric
      point 4.62. According to SDS-PAGE analysis and FPLC result, DyPPa mainly existed
      as homodimer (64 kDa). DyPPa displayed typical heme absorbance of Soret band,
      with an Rz value of 1.18. Inductively coupled plasma-atomic absorption spectrum
      data also indicated DyPPa contained iron. Multiple amino acid sequence alignment
      of DyPPa with other members of the DyP-type peroxidases family showed the
      presence of conserved D139, H210, and R227 amino acids and GXXDG motifs, which
      were commonly shared by the DyP-type peroxidase family. Although the primary
      structure homology between DyPPa and other family members was very low, their
      secondary and tertiary structure displayed high homology, which explained the
      high decolorizing activity of DyPPa. Specifically, DyPPa displayed a good thermal
      stability and maximal activity on Reactive blue 5 under pH 3.5. Therefore, it was
      proposed that DyPPa, with a wide range of substrate specificity, was a novel
      member of the DyP-type peroxidases family.

PMID- 22161143
TI  - TGF-beta-induced epithelial-mesenchymal transition of A549 lung adenocarcinoma
      cells is enhanced by pro-inflammatory cytokines derived from RAW 264.7 macrophage
      cells.
AB  - Cancer cells undergo epithelial-mesenchymal transition (EMT) during invasion and
      metastasis. Although transforming growth factor-beta (TGF-beta) and pro
      inflammatory cytokines have been implicated in EMT, the underlying molecular
      mechanisms remain to be elucidated. Here, we studied the effects of
      proinflammatory cytokines derived from the mouse macrophage cell line RAW 264.7
      on TGF-beta-induced EMT in A549 lung cancer cells. Co-culture and treatment with
      conditioned medium of RAW 264.7 cells enhanced a subset of TGF-beta-induced EMT
      phenotypes in A549 cells, including changes in cell morphology and induction of
      mesenchymal marker expression. These effects were increased by the treatment of
      RAW 264.7 cells with lipopolysaccharide, which also induced the expression of
      various proinflammatory cytokines, including TNF-alpha and IL-1beta. The effects
      of conditioned medium of RAW 264.7 cells were partially inhibited by a TNF-alpha
      neutralizing antibody. Dehydroxy methyl epoxyquinomicin, a selective inhibitor of
      NFkappaB, partially inhibited the enhancement of fibronectin expression by TGF
      beta, TNF-alpha, and IL-1beta, but not of N-cadherin expression. Effects of other
      pharmacological inhibitors also suggested complex regulatory mechanisms of the
      TGF-beta-induced EMT phenotype by TNF-alpha stimulation. These findings provide
      direct evidence of the effects of RAW 264.7-derived TNF-alpha on TGF-beta-induced
      EMT in A549 cells, which is transduced in part by NFkappaB signalling.

PMID- 22161142
TI  - Macrophages participate in IL-17-mediated inflammation.
AB  - The involvement of macrophages (MPhis) in Th17-cell responses is still poorly
      understood. While neutrophils are thought to be the predominant effector of Th17
      cell responses, IL-17 is also known to induce myelotropic chemokines and growth
      factors. Other T-cell-derived cytokines induce non-classical functions,
      suggesting that IL-17 sigxnaling may similarly elicit unique MPhi functions.
      Here, we characterized the expression of subunits of the IL-17 receptor on
      primary murine MPhis from different anatomical compartments. The greatest
      expression of IL-17 receptors was observed on mucosal Ly6C(hi)  "inflammatory"
      MPhis. We further observed upregulation of IL-17 receptors in vitro on bone
      marrow-derived macrophages (BMMPhis) in response to peptidoglycan or CpG
      oligonucleotide stimuli, and in vivo, upon CFA administration. Macrophages
      expressing IL-17 receptors were observed infiltrating the hearts of mice with
      myocarditis, and genetic ablation of IL-17RA altered MPhi recruitment. Treating
      primary MPhis from a wide variety of different anatomic sources (as well as cell
      lines) with IL-17A induced the production of unique profiles of cytokines and
      chemokines, including GM-CSF, IL-3, IL-9, CCL4/MIP-1beta and CCL5/RANTES. IL-17A
      also induced production of IL-12p70; IL-17-signaling-deficient MPhis elicited
      diminished IFN-gamma production by responding DO11.10 CD4(+)  T cells when used
      as APCs. These data indicate that MPhis from different anatomic locations direct
      IL-17-mediated responses.

PMID- 22161144
TI  - Effect of particle size of titanium dioxide nanoparticle aggregates on the
      degradation of one azo dye.
AB  - INTRODUCTION: Titanium dioxide (TiO(2)) nanoparticle powders have been
      extensively studied to quickly photodegrade some organic pollutants; however, the
      effect of the particle size of TiO(2) nanoparticle aggregates on degradation
      remains unclear because microscale aggregates form once the nanoparticle powders
      enter into water. METHODS: The degradation of azo dye by different particle sizes
      of TiO(2) nanoparticle aggregates controlled by NaCl concentrations was
      investigated to evaluate the particle size effect. Removal reactions of reactive
      black 5 (RB5) with TiO(2) nanoparticles followed pseudo-first-order kinetics.
      RESULTS: The increase of TiO(2) dosage from 40 to 70 mg/L enhanced the
      degradation. At doses around 100 mg/L TiO(2), degradation rates decreased which
      could be the result of poor UV light transmittance at high-particle
      concentrations. At average particle sizes of TiO(2) nanopowders less than around
      500 nm, the degradation rates increased with decreasing particle size. As the
      average particle size exceeded 500 nm, the degradation rates were not
      significantly changed. CONCLUSIONS: For the complete degradation experiments, the
      mineralization rates of total organic carbon disappearance are generally
      following the RB5 decolorization kinetic trend. These findings can facilitate the
      application of TiO(2) nanoparticles to the design of photodegradation treatments
      for wastewater.

PMID- 22161145
TI  - Effects of phosphorus amendments and plant growth on the mobility of Pb, Cu, and
      Zn in a multi-metal-contaminated soil.
AB  - PURPOSE: Phosphorus amendments have been widely and successfully used in
      immobilization of one single metal (e.g., Pb) in contaminated soils. However,
      application of P amendments in the immobilization of multiple metals and
      particularly investigations about the effects of planting on the stability of the
      initially P-induced immobilized metals in the contaminated soils are far limited.
      METHODS: This study was conducted to determine the effects of phosphate rock
      tailing (PR), triple superphosphate fertilizer (TSP), and their combination (P+T)
      on mobility of Pb, Cu, and Zn in a multimetal-contaminated soil. Chinese cabbage
      (Brassica rapa subsp. chinensis) (metal-sensitive) and Chinese kale (Brassica
      alboglabra Bailey) (metal-resistant) were introduced to examine the effects of
      planting on leaching of Pb, Cu, and Zn in the P-amended soils. RESULTS: All three
      P treatments greatly reduced CaCl(2)-extractable Pb and Zn by 55.2-73.1% and 14.3
      33.6%, respectively. The PR treatment decreased CaCl(2)-extractable Cu by 27.8%,
      while the TSP and P+T treatments increased it by 47.2% and 44.4%, respectively.
      All three P treatments were effective in reducing simulated rainwater leachable
      Pb, with dissolved and total leachable Pb decrease by 15.6-81.9% and 16.3-64.5%,
      respectively. The PR treatment reduced the total leachable Zn by 16.8%, while TSP
      and P+T treatments increased Zn leaching by 92.7% and 78.9%, respectively.
      However, total Cu leaching were elevated by 17.8-178% in all P treatments.
      Planting promoted the leaching of Pb and Cu by 98.7-127% and 23.5-170%,
      respectively, especially in the colloid fraction, whereas the leachable Zn was
      reduced by 95.3-96.5% due to planting. The P treatments reduced the uptake of Pb,
      Cu, and Zn in the aboveground parts of Chinese cabbage by up to 65.1%, 34.3%, and
      9.59%, respectively. Though P treatments were effective in reducing Zn
      concentrations in the aboveground parts of the metal-resistant Chinese kale by
      22.4-28.9%, they had little effect on Pb and Cu uptake. CONCLUSIONS: The results
      indicated that all P treatments were effective in immobilizing Pb. The effect on
      the immobilization of Cu and Zn varied with the different P treatments and
      evaluation methods. Metal-sensitive plants are more responsive to the P
      treatments than metal-resistant plants. Planting affects leaching of metals in
      the P-amended soils, specially leaching of colloid fraction. The conventional
      assessment on leaching risks of heavy metals by determining dissolved metals
      (filtered through 0.45-MUm pore size membrane) in leachates could be
      underestimated since colloid fraction may also contribute to the leaching.

PMID- 22161147
TI  - Between candidate genes and whole genomes: time for alternative approaches in
      blood pressure genetics.
AB  - Blood pressure has a significant genetic component, but less than 3% of the
      observed variance has been attributed to genetic variants identified to date.
      Candidate gene studies of rare, monogenic hypertensive syndromes have
      conclusively implicated several genes altering renal sodium balance, and studies
      of essential hypertension have inconsistently implicated over 50 genes in
      pathways affecting renal sodium balance and other functions. Genome-wide linkage
      scans have replicated numerous quantitative trait loci throughout the genome, and
      over 50 single nucleotide polymorphisms (SNPs) have been replicated in multiple
      genome-wide association studies. These studies provide considerable evidence that
      epistasis and other interactions play a role in the genetic architecture of blood
      pressure regulation, but candidate gene studies have limited scope to test for
      epistasis, and genome-wide studies have low power for both main effects and
      interactions. This review summarizes the genetic findings to date for blood
      pressure, and it proposes focused, pathway-based approaches involving epistasis,
      gene-environment interactions, and next-generation sequencing to further the
      genetic dissection of blood pressure and hypertension.

PMID- 22161146
TI  - Removal of arsenate from groundwater by electrocoagulation method.
AB  - PURPOSE: Arsenic, a toxic metalloid in drinking water, has become a major threat
      for human beings and other organisms. In the present work, attempts have been
      made to remove arsenate from the synthetic as well as natural water of Ballia
      district, India by electrocoagulation method. Efforts have also been made to
      optimize the various parameters such as initial arsenate concentration, pH,
      applied voltage, processing time, and working temperature. METHOD:
      Electrocoagulation is a fast, inexpensive, selective, accurate, reproducible, and
      eco-friendly method for arsenate removal from groundwater. The present paper
      describes an electrocoagulation method for arsenate removal from groundwater
      using iron and zinc as anode and cathode, respectively. RESULTS: The maximum
      removal of arsenate was 98.8% at 2.0 mg L(-1), 7.0, 3.0 V, 10.0 min, and 30
      degrees C as arsenate concentration, pH, applied voltage, processing time, and
      working temperature, respectively. Relative standard deviation, coefficient of
      determination (r (2)), and confidence limits were varied from 1.50% to 1.59%,
      0.9996% to 0.9998%, and 96.0% to 99.0%, respectively. The treated water was
      clear, colorless, and odorless without any secondary contamination. The developed
      and validated method was applied for arsenate removal of two samples of
      groundwater of Ballia district, U.P., India, having 0.563 to 0.805 mg L(-1),
      arsenate concentrations. CONCLUSIONS: The reported method is capable for the
      removal of arsenate completely (100% removal) from groundwater of Ballia
      district. There was no change in the groundwater quality after the removal of
      arsenate. The treated water was safe for drinking, bathing, and recreation
      purposes. Therefore, this method may be the choice of arsenate removal from
      natural groundwater.

PMID- 22161148
TI  - Scaffold hopping for identification of novel D(2) antagonist based on 3D
      pharmacophore modelling of illoperidone analogs.
AB  - The dopamine D(2) receptor is involved in the etiology of a number of disorders,
      such as Parkinson's disease, Huntington's Chorea, tardive dyskinesia and
      schizophrenia. Antagonism of D(2) receptors is implicated in the treatment of
      various psychiatric disorders. In order to understand essential structural
      features required for D(2) antagonism, this research article elaborates on the
      generation of a four-point 3D pharmacophore model which was extracted from a
      series of 45 novel 3-[[(aryloxy)alkyl]piperidinyl]-1,2-benzisoxazole derivatives.
      The best pharmacophore model generated consisted of four PRRR features: a
      positively charged group (P), and three aromatic rings (R). Based on the model
      generated, a statistically valid 3D-QSAR with good predictability (Q(2) = 0.756)
      was derived. For the validation of the pharmacophore hypothesis, active compounds
      were docked against the 3D structure of the D(2) receptor which was constructed
      through homology modeling. Further, the derived pharmacophore was used as a query
      to search the Zinc 'clean drug-like' database. Hits retrieved were passed
      progressively through filters, such as fitness score, predicted activity and
      docking scores. The resulting hits present new scaffolds with a strong potential
      for D(2) antagonist.

PMID- 22161149
TI  - Interest and use of mental health and specialty behavioral medicine counseling in
      US primary care patients.
AB  - BACKGROUND: Counseling interventions have the potential to improve health and
      quality of life for primary care patients, but there are few studies describing
      the interest in and utilization of counseling among this patient population in
      the USA. PURPOSE: The purpose of the study was to evaluate interest in mental
      health and specialty behavioral medicine counseling and predictors of utilization
      over 1 year among US primary care patients. METHOD: Participants in this two
      survey longitudinal study included 658 primary care patients in an urban US
      academic medical center (461 females, age M = 51.05, SD = 15.46 years). Retention
      rate was 61.2% at survey 2. Patient demographics, depression, anxiety, and
      interest in counseling services were assessed through a survey mailed 1 week
      following an outpatient appointment. Respondents to survey 1 were re-contacted 1
      year later to assess. Interest and use of the following counseling services were
      evaluated in the relevant subgroups: mental health (the entire sample and
      patients with elevated anxiety and/or depression), health/lifestyle (overweight
      and obese participants), smoking cessation (current and occasional smokers), and
      pain management (participants with elevated daily pain ratings). RESULTS: At
      survey 1, 45.7% of the sample reported interest in mental health counseling, and
      58.9% of the sample reported interest in behavioral medicine counseling. Among
      overweight or obese participants, 59.9% were interested in health/lifestyle
      counseling. Among smokers, 55.3% were interested in smoking cessation, and among
      participants with chronic pain, 33.8% were interest in pain management. Rates of
      utilization of services at survey 2 were 21.3% for mental health, 7.7% for
      health/lifestyle, 6.7% for smoking cessation, and 6.6% for pain management.
      Interest in receiving services at survey 1 was the strongest predictor of
      utilization. CONCLUSION: Results demonstrate high interest but low utilization
      over 1 year among US primary care patients. Identifying patients interested in
      counseling services and reducing barriers may help facilitate receipt of services
      for those with interest and need for behavioral treatments.

PMID- 22161150
TI  - Systematic review of intervention practices for depression in the workplace.
AB  - DESIGN: Systematic Review. OBJECTIVE: To determine which intervention approaches
      to manage depression in the workplace have been successful and yielded value for
      employers in developed economies. DATA SOURCES: We searched MEDLINE, EMBASE,
      CINAHL, Central, PsycINFO, and Business Source Premier up to June 2010 using
      search terms in four broad areas: work setting, depression, intervention, and
      work outcomes. STUDY SELECTION: Two independent reviewers selected potential
      articles that met the following criteria: working age individuals with mild or
      moderate depression; interventions or programs that were workplace-based or could
      be implemented and/or facilitated by the employer; inclusion of a comparator
      group in the analysis; outcomes of prevention, management, and recurrences of
      work disability or sickness absence, and work functioning. METHODS: Two reviewers
      independently reviewed each article for quality and extracted data using
      standardised forms. Following guidelines from the GRADE Working Group, the
      quality of evidence addressing each outcome was graded as high, moderate, low, or
      very low on the basis of six criteria: study design, risk of bias, consistency,
      generalisability, data precision, and economic benefit. Using this information
      and following Cochrane Collaboration guidelines, the findings for each
      intervention were summarised and key messages were developed. RESULTS: We
      identified ten randomised trials and two non-randomised studies from various
      countries and jurisdictions that evaluated a wide range of intervention
      practices. The evidence was graded as "very low" for all outcomes identified.
      Therefore, no intervention could be recommended. CONCLUSIONS: To date, there is
      insufficient quality of evidence to determine which interventions are effective
      and yield value to manage depression in the workplace.

PMID- 22161152
TI  - Disentangling the associations between autistic-like and internalizing traits: a
      community based twin study.
AB  - Internalizing difficulties are prevalent in children with autism spectrum
      disorders (ASD), yet little is known about the underlying cause of this
      comorbidity. It is also unclear which types of autistic-like and internalizing
      difficulties are most strongly associated. The current study investigated the
      phenotypic and etiological associations between specific autistic-like traits and
      internalizing traits within a population-based sample. Parent-reported data were
      analyzed from 7,311 twin pairs at age 7 to 8 years. Structural equation modeling
      revealed distinguishable patterns of overlap between the three autistic-like
      traits (social difficulties, communication problems and repetitive/restricted
      behaviors) and four subtypes of internalizing traits (social anxiety, fears,
      generalized anxiety, negative affect). Although all phenotypic associations were
      modest (rph = 0.00-0.36), autistic-like communication impairments and
      repetitive/restricted behaviors correlated most strongly with generalized anxiety
      and negative affect both phenotypically and genetically. Conversely, autistic
      like social difficulties showed little overlap with internalizing behaviors.
      Disentangling these associations and their etiological underpinnings may help
      contribute to the conceptualization and diagnosis of 'comorbidity' within ASD and
      internalizing disorders.

PMID- 22161153
TI  - Spatial distribution of calcium in food, water and soil and its possible
      influence on rickets disease in Northern Nigeria.
AB  - Since the 1990s, children of the Gbagyi tribe in Northern Nigeria have been
      suffering severe rickets with an incidence of up to 40% in the children's
      generation. The disease seems to be prevalent in an area of approximately 100
      km(2) south-east of Kaduna. According to broad medical studies in that area,
      there is no evidence for a genetic disposition but for a nutritional cause of the
      disease. A lack of calcium was found in blood and was calculated to originate
      from diet. We therefore checked parent material, soil, maize cobs (Zea mays) and
      drinking water for their specific Ca contents from a region with rickets problem
      (study area A) and compared the results to Ca amounts in similar samples from a
      region where rickets is unknown among the Gbagyi population (study area B). It
      thereby became apparent that there are no differences in mineralogical
      composition of the parent material between the study areas, but that Ca contents
      in soil, maize cobs and drinking water are 47.6%, 26.6%, respectively, 79.1%
      lower in study area A compared to study area B. This result suggests that there
      may indeed be a nutritionally and/or environmentally influence on rickets
      disease. Nevertheless, further research on this topic is required.

PMID- 22161151
TI  - Herbivore-induced changes in tomato (Solanum lycopersicum) primary metabolism: a
      whole plant perspective.
AB  - Induced changes in primary metabolism are important plant responses to herbivory,
      providing energy and metabolic precursors for defense compounds. Metabolic shifts
      also can lead to reallocation of leaf resources to storage tissues, thus
      increasing a plant's tolerance. We characterized whole-plant metabolic responses
      of tomato (Solanum lycopersicum) 24 h after leaf herbivory by two caterpillars
      (the generalist Helicoverpa zea and the specialist Manduca sexta) by using GC-MS.
      We measured 56 primary metabolites across the leaves, stems, roots, and apex,
      comparing herbivore-attacked plants to undamaged plants and mechanically damaged
      plants. Induced metabolic change, in terms of magnitude and number of individual
      concentration changes, was stronger in the apex and root tissues than in
      undamaged leaflets of damaged leaves, indicating rapid and significant whole
      plant responses to damage. Helicoverpa zea altered many more metabolites than M.
      sexta across most tissues, suggesting an enhanced plant response to H. zea
      herbivory. Helicoverpa zea herbivory strongly affected concentrations of defense
      related metabolites (simple phenolics and precursor amino acids), while M. sexta
      altered metabolites associated with carbon and nitrogen transport. We conclude
      that herbivory induces many systemic primary metabolic changes in tomato, and
      that changes often are specific to a single tissue or type of herbivore. The
      potential implications of primary metabolic changes are discussed in relation to
      resistance and tolerance.

PMID- 22161154
TI  - The concentration and distribution of organochlorine pesticides in the air from
      the karst cave, South China.
AB  - Organochlorine pesticides (OCPs) in the air of Dayan Cave in Guilin were
      analyzed, to investigate the source and contamination levels. Generally, air
      outside of the cave had much higher concentrations than inside air, and both
      outside and inside air showed much lower contamination levels than those observed
      in other regions in China and abroad. The ratios of alpha-/gamma-HCHs and the
      percentages of beta-(or delta-)HCH implied a residue of historical local
      technical HCH contamination. The DDT concentrations, o,p'-DDT/p,p'-DDT, and p,p'
      DDE/p,p'-DDT suggested fresh DDT-containing products acted as the primary source
      of DDT for the air in Dayan Cave. An intermediate level concentration of alpha
      endosulfan (156.00 pg/m(3)) was observed in the outside air, implying local
      source was dominant. Based on the similar sources of HCH and DDT and the
      relationships between outside and inside air, it appeared that outside air
      pollutants affected on inside HCH and DDT's distribution. For other OCPs, outside
      air might be major contributor to inside air contamination under conditions of
      high concentrations in outside air compared with low levels in inside air for
      semi-closed karstic caves.

PMID- 22161155
TI  - Recurrent inflammatory pseudotumor of the jaw with perineural intracranial
      invasion demonstrating sustained response to Rituximab.
AB  - Corticosteroids are the mainstay of treatment of inflammatory pseudotumor (IPT)
      of the head and neck; however, involvement of the skull base and mandible can be
      unresponsive to steroids and require surgical resection. IPT is known to usually
      contain a CD20+ lymphocyte subgroup. Rituximab, a chimeric anti-CD20 antibody,
      has been successfully utilized in the treatment of other CD20+ diseases,
      including the similar idiopathic orbital inflammatory disease. This is the first
      report to describe successful treatment with Rituximab of a recurrent IPT of the
      mandible with trigeminal spread and leptomeningeal involvement with clinical and
      radiologic evidence demonstrating a sustained response to therapy.

PMID- 22161156
TI  - Reciprocal expression of survivin and SMAC/DIABLO in primary breast cancer.
AB  - There is an intimate relation between disturbance in survivin and SMAC/DIABLO
      expressions and cancer formation in many tissues; however, this was not confirmed
      in the primary breast cancer. The aim of this study was to evaluate the
      relationship between survivin and SMAC/DIABLO mRNA expressions in primary breast
      cancer using RT-PCR and their relationship to some of the risk factors (age,
      family history, breast-feeding, use of contraceptive pills and hormonal
      receptors). Breast cancer tissues were studied for the detection of the mRNA
      expression of survivin and SMAC/DIABLO. This was done by qualitative reverse
      transcription-polymerase chain reaction (RT-PCR). SMAC/DIABLO mRNA was detected
      by RT-PCR only in 1 sample in breast cancer tissues (6.25%). However, it was
      expressed in 16 out of 25 (64%) of the benign tumor tissues (P=0.00). In
      contrast, survivin mRNA was highly expressed in breast cancer tissues, 36 out of
      48 (75%) (P=0.00), while its expression was very low in benign tumor tissues,
      only 1 out of 37 (2.7%) (P=0.00). Expressions of SMAC/DIABLO and survivin were
      significantly reciprocal in breast cancer and benign tumor tissues. SMAC/DIABLO
      inhibits apoptosis of breast cancer cells by suppression of survivin. These two
      genes probably form an important link in the signaling pathway of formation of
      breast cancer cells, which may be chosen as therapeutic targets in the primary
      breast cancer.

PMID- 22161157
TI  - Weapons ovarian epithelial tumors may use in immune escape: an
      immunohistochemical correlational study.
AB  - Investigate FasL and survivin expression in a series of primary ovarian surface
      epithelial tumors, correlate their expression with each other, and characterize
      the presence of CD3+ T-lymphocytes in studied tumors and determine whether their
      presence correlates with FasL or survivin expression in malignant cases. FasL and
      survivin expression was assessed in 54 ovarian epithelial tumors. The results
      were compared between different tumor types and grades. Correlation between both
      markers' expression in all studied tumors was done. Either marker's expression
      was compared to the mean CD3+ T-lymphocytes per HPF in the studied malignant
      tumors. Either FasL or survivin expression was significantly higher in malignant
      versus benign ovarian epithelial tumors (p < 0.001 for both) and both markers
      were strongly correlated to each other (r = 0.877 & p < 0.001). Malignant tumors
      show significantly higher mean CD3+ T-lymphocytes than benign and borderline
      tumors. The mean CD3+ T-lymphocytes decrease significantly on increasing
      malignant tumor grade (p = 0.019) and expression of both FasL and survivin (r = 
      0.729, -0.582, respectively & p < 0.001 for both). The higher expression of FasL
      and survivin in malignant as compared to benign ovarian tumors suggest that they
      have a significant role in pathogenesis of ovarian carcinoma. Both markers are
      strongly correlated to each other and may contribute to immune escape of ovarian
      carcinoma as their higher expression is associated with decreased number of CD3 +
      T-lymphocytes.

PMID- 22161158
TI  - Depressive symptoms and impaired physical function after acute lung injury: a 2
      year longitudinal study.
AB  - RATIONALE: Survivors of acute lung injury (ALI) frequently have substantial
      depressive symptoms and physical impairment, but the longitudinal epidemiology of
      these conditions remains unclear. OBJECTIVES: To evaluate the 2-year incidence
      and duration of depressive symptoms and physical impairment after ALI, as well as
      risk factors for these conditions. METHODS: This prospective, longitudinal cohort
      study recruited patients from 13 intensive care units (ICUs) in four hospitals,
      with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital
      Anxiety and Depression Scale depression score greater than or equal to 8
      ("depressive symptoms") in patients without a history of depression before ALI,
      and two or more dependencies in instrumental activities of daily living
      ("impaired physical function") in patients without baseline impairment.
      MEASUREMENTS AND MAIN RESULTS: During 2-year follow-up of 186 ALI survivors, the
      cumulative incidences of depressive symptoms and impaired physical function were
      40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal
      durations were greater than 21 months for each outcome. Risk factors for incident
      depressive symptoms were education 12 years or less, baseline disability or
      unemployment, higher baseline medical comorbidity, and lower blood glucose in the
      ICU. Risk factors for incident impaired physical function were longer ICU stay
      and prior depressive symptoms. CONCLUSIONS: Incident depressive symptoms and
      impaired physical function are common and long-lasting during the first 2 years
      after ALI. Interventions targeting potentially modifiable risk factors (e.g.,
      substantial depressive symptoms in early recovery) should be evaluated to improve
      ALI survivors' long-term outcomes.

PMID- 22161159
TI  - Critical role of the axonal guidance cue EphrinB2 in lung growth, angiogenesis,
      and repair.
AB  - RATIONALE: Lung diseases characterized by alveolar damage currently lack
      efficient treatments. The mechanisms contributing to normal and impaired alveolar
      growth and repair are incompletely understood. Axonal guidance cues (AGC) are
      molecules that guide the outgrowth of axons to their targets. Among these AGCs,
      members of the Ephrin family also promote angiogenesis, cell migration, and
      organogenesis outside the nervous system. The role of Ephrins during alveolar
      growth and repair is unknown. OBJECTIVES: We hypothesized that EphrinB2 promotes
      alveolar development and repair. METHODS: We used in vitro and in vivo
      manipulation of EphrinB2 signaling to assess the role of this AGC during normal
      and impaired lung development. MEASUREMENTS AND MAIN RESULTS: In vivo EphrinB2
      knockdown using intranasal siRNA during the postnatal stage of alveolar
      development in rats arrested alveolar and vascular growth. In a model of O(2)
      induced arrested alveolar growth in newborn rats, air space enlargement, loss of
      lung capillaries, and pulmonary hypertension were associated with decreased lung
      EphrinB2 and receptor EphB4 expression. In vitro, EphrinB2 preserved alveolar
      epithelial cell viability in O(2), decreased O(2)-induced alveolar epithelial
      cell apoptosis, and accelerated alveolar epithelial cell wound healing,
      maintained lung microvascular endothelial cell viability, and proliferation and
      vascular network formation. In vivo, treatment with intranasal EphrinB2 decreased
      alveolar epithelial and endothelial cell apoptosis, preserved alveolar and
      vascular growth in hyperoxic rats, and attenuated pulmonary hypertension.
      CONCLUSION: The AGC EphrinB2 may be a new therapeutic target for lung repair and
      pulmonary hypertension.

PMID- 22161160
TI  - Activin-A overexpression in the murine lung causes pathology that simulates acute
      respiratory distress syndrome.
AB  - RATIONALE: Activin-A is up-regulated in various respiratory disorders. However,
      its precise role in pulmonary pathophysiology has not been adequately
      substantiated in vivo. OBJECTIVES: To investigate in vivo the consequences of
      dysregulated Activin-A expression in the lung and identify key Activin-A-induced
      processes that contribute to respiratory pathology. METHODS: Activin-A was
      ectopically expressed in murine lung, and functional, structural, and molecular
      alterations were extensively analyzed. The validity of Activin-A as a therapeutic
      target was demonstrated in animals overexpressing Activin-A or treated with
      intratracheal instillation of LPS. Relevancy to human pathology was substantiated
      by demonstrating high Activin-A levels in bronchoalveolar lavage (BAL) samples
      from patients with acute respiratory distress syndrome (ARDS). MEASUREMENTS AND
      MAIN RESULTS: Overexpression of Activin-A in mouse airways caused pulmonary
      pathology reminiscent of acute lung injury (ALI)/ARDS. Activin-A triggered a
      lasting inflammatory response characterized by acute alveolar cell death and
      hyaline membrane formation, sustained up-regulation of high-mobility group box 1,
      development of systemic hypercoagulant state, reduction of surfactant proteins
      SpC, SpB, and SpA, decline of lung compliance, transient fibrosis, and eventually
      emphysema. Therapeutic neutralization of Activin-A attenuated the ALI/ARDS-like
      pathology induced either by ectopic expression of Activin-A or by intratracheal
      instillation of LPS. In line with the similarity of the Activin-A-induced
      phenotype to human ARDS, selective up-regulation of Activin-A was found in BAL of
      patients with ARDS. CONCLUSIONS: Our studies demonstrate for the first time in
      vivo the pathogenic consequences of deregulated Activin-A expression in the lung,
      document novel aspects of Activin-A biology that provide mechanistic explanation
      for the observed phenotype, link Activin-A to ALI/ARDS pathophysiology, and
      provide the rationale for therapeutic targeting of Activin-A in these disorders.

PMID- 22161161
TI  - Risk of tuberculosis in pregnancy: a national, primary care-based cohort and self
      controlled case series study.
AB  - OBJECTIVES: Tuberculosis (TB) disease adversely affects mother and child, and
      strategies to control TB in this group are important. The aim of this study was
      to analyze the epidemiology of TB in pregnancy, and to establish whether
      pregnancy is an independent risk factor for TB. METHODS: The United Kingdom-wide
      cohort study was based on the General Practitioner Research Database (GPRD),
      enrolling all women with pregnancies between 1996 and 2008. Incidence rates and
      incidence rate ratios (IRRs) of TB events during pregnancy, 6 months postpartum,
      and outside pregnancy were calculated and compared by Poisson regression. A
      nested self-controlled case series compared the risk of TB in these periods,
      adjusting for individual and time-bound confounders. MEASUREMENTS AND MAIN
      RESULTS: The crude TB rate for the combined pregnancy and postpartum period was
      15.4 per 100,000 person-years, significantly higher than outside of pregnancy
      (9.1 per 100,000 person-years; P = 0.02). Adjusting for age, region, and
      socioeconomic status the postpartum TB risk was significantly higher than outside
      pregnancy (IRR, 1.95; 95% confidence interval [CI], 1.24-3.07), whereas there was
      no significant increase during pregnancy (IRR, 1.29; 95% CI, 0.82-2.03). These
      observations were confirmed in the self-controlled case series (IRR, 1.62; 95%
      CI, 1.01-2.58 and IRR, 1.03; 95% CI, 0.64-1.65, respectively). CONCLUSIONS: The
      incidence of TB diagnosis is significantly increased postpartum. Although we did
      not find an increase during pregnancy, the postpartum incidence may reflect an
      increase during pregnancy given diagnostic, immunological and administrative
      delays. Clinicians' awareness should be improved and the effectiveness of public
      health policy measures such as targeted screening of pregnant and postpartum
      women in high-risk groups should be evaluated.

PMID- 22161162
TI  - Discordance among commercially available diagnostics for latent tuberculosis
      infection.
AB  - RATIONALE: There is uncertainty regarding how to interpret discordance between
      tests for latent tuberculosis infection. OBJECTIVES: The objective of this study
      was to assess discordance between commercially available tests for latent
      tuberculosis in a low-prevalence population, including the impact of
      nontuberculous mycobacteria. METHODS: This was a cross-sectional comparison study
      among 2,017 military recruits at Fort Jackson, South Carolina, from April to June
      2009. Several tests were performed simultaneously with a risk factor
      questionnaire, including (1) QuantiFERON-TB Gold In-Tube test, (2) T-SPOT.TB
      test, (3) tuberculin skin test, and (4) Battey skin test using purified protein
      derivative from the Battey bacillus. MEASUREMENTS AND MAIN RESULTS: In this low
      prevalence population, the specificities of the three commercially available
      diagnostic tests were not significantly different. Of the 88 subjects with a
      positive test, only 10 (11.4%) were positive to all three tests; 20 (22.7%) were
      positive to at least two tests. Bacille Calmette-Guerin vaccination, tuberculosis
      prevalence in country of birth, and Battey skin test reaction size were
      associated with tuberculin skin test-positive, IFN-gamma release assay-negative
      test discordance. Increasing agreement between the three tests was associated
      with epidemiologic criteria indicating risk of infection and with quantitative
      test results. CONCLUSIONS: For most positive results the three tests identified
      different people, suggesting that in low-prevalence populations most discordant
      results are caused by false-positives. False-positive tuberculin skin test
      reactions associated with reactivity to nontuberculous mycobacteria and bacille
      Calmette-Guerin vaccination may account for a proportion of test discordance
      observed.

PMID- 22161163
TI  - Variable DNA methylation is associated with chronic obstructive pulmonary disease
      and lung function.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with local
      (lung) and systemic (blood) inflammation and manifestations. DNA methylation is
      an important regulator of gene transcription, and global and specific gene
      methylation marks may vary with cigarette smoke exposure. OBJECTIVES: To perform
      a comprehensive assessment of methylation marks in DNA from subjects well
      phenotyped for nonneoplastic lung disease. METHODS: We conducted array-based
      methylation screens, using a test-replication approach, in two family-based
      cohorts (n = 1,085 and 369 subjects). MEASUREMENTS AND MAIN RESULTS: We observed
      349 CpG sites significantly associated with the presence and severity of COPD in
      both cohorts. Seventy percent of the associated CpG sites were outside of CpG
      islands, with the majority of CpG sites relatively hypomethylated. Gene ontology
      analysis based on these 349 CpGs (330 genes) suggested the involvement of a
      number of genes responsible for immune and inflammatory system pathways,
      responses to stress and external stimuli, as well as wound healing and
      coagulation cascades. Interestingly, our observations include significant,
      replicable associations between SERPINA1 hypomethylation and COPD and lower
      average lung function phenotypes (combined P values: COPD, 1.5 * 10(-23);
      FEV(1)/FVC, 1.5 * 10(-35); FEV(1), 2.2 * 10(-40)). CONCLUSIONS: Genetic and
      epigenetic pathways may both contribute to COPD. Many of the top associations
      between COPD and DNA methylation occur in biologically plausible pathways. This
      large-scale analysis suggests that DNA methylation may be a biomarker of COPD and
      may highlight new pathways of COPD pathogenesis.

PMID- 22161164
TI  - Inhibition of microRNA-17 improves lung and heart function in experimental
      pulmonary hypertension.
AB  - RATIONALE: MicroRNAs (miRs) control various cellular processes in tissue
      homeostasis and disease by regulating gene expression on the posttranscriptional
      level. Recently, it was demonstrated that the expression of miR-21 and members of
      the miR-17-92 cluster was significantly altered in experimental pulmonary
      hypertension (PH). OBJECTIVES: To evaluate the therapeutic efficacy and
      antiremodeling potential of miR inhibitors in the pathogenesis of PH. METHODS: We
      first tested the effects of miR inhibitors (antagomirs), which were specifically
      designed to block miR-17 (A-17), miR-21 (A-21), and miR-92a (A-92a) in chronic
      hypoxia-induced PH in mice and A-17 in monocrotaline-induced PH in rats.
      Moreover, biological function of miR-17 was analyzed in cultured pulmonary artery
      smooth muscle cells. MEASUREMENTS AND MAIN RESULTS: In the PH mouse model, A-17
      and A-21 reduced right ventricular systolic pressure, and all antagomirs
      decreased pulmonary arterial muscularization. However, only A-17 reduced hypoxia
      induced right ventricular hypertrophy and improved pulmonary artery acceleration
      time. In the monocrotaline-induced PH rat model, A-17 treatment significantly
      decreased right ventricular systolic pressure and total pulmonary vascular
      resistance index, increased pulmonary artery acceleration time, normalized
      cardiac output, and decreased pulmonary vascular remodeling. Among the tested miR
      17 targets, the cyclin-dependent kinase inhibitor 1A (p21) was up-regulated in
      lungs undergoing A-17 treatment. Likewise, in human pulmonary artery smooth
      muscle cells, A-17 increased p21. Overexpression of miR-17 significantly reduced
      p21 expression and increased proliferation of smooth muscle cells. CONCLUSIONS:
      Our data demonstrate that A-17 improves heart and lung function in experimental
      PH by interfering with lung vascular and right ventricular remodeling. The
      beneficial effects may be related to the up-regulation of p21. Thus, inhibition
      of miR-17 may represent a novel therapeutic concept to ameliorate disease state
      in PH.

PMID- 22161165
TI  - [Deep brain stimulation in Parkinson's disease: overview on the pros and cons of
      an effective therapy].

PMID- 22161166
TI  - [Psychiatric side effects of deep brain stimulation in Parkinson's disease].
AB  - Since the 1990 s deep brain stimulation (DBS) has provided an effective tool for
      the treatment of Parkinson's disease. About fifty thousand Parkinson patients
      have been treated by DBS so far. Although a relatively safe intervention, there
      are still some considerable side effects, psychiatric and non-psychiatric. We
      conducted a structured search using PubMed and included publications from 1999 to
      February 2011 to provide an overview of the current data concerning psychiatric
      side effects of DBS in Parkinson's disease. There was a tremendous variety and
      inconsistency concerning methods and results of the studies we included. However,
      it became apparent that postoperatively increased attention should be paid
      concerning a potentially increased suicidality and affective alterations
      (particularly manic states). We suggest frequent pre- and postoperative
      evaluations of Parkinson patients treated with DBS.

PMID- 22161167
TI  - [Neurobiology, clinical characteristics and therapy in Tourette's syndrome].
AB  - Tourette's syndrome (TS) is characterised by motor and vocal tics. The clinical
      manifestation during childhood and the frequent remission during early adulthood
      point to a dysregulation in the maturation of neuronal pathways. As a
      neurobiological correlate, the cortico-striato-thalamo-cortical circuit is the
      main focus of research. Two main features of a movement, the speed and direction
      of a movement, are controlled by the basal ganglia. Both features are
      dysregulated in TS.  Besides the motor symptoms, patients with TS suffer from
      comorbidities such as attention deficit hyperactivity syndrome, depression and
      obsessive compulsive disorders. Tics are modified in frequency and intensity by
      actions that require a high level of concentration such as reading or by
      distress, e.g., teasing by peers. The results of structural and functional
      imaging data support the hypothesis of altered signal transmission in the basal
      ganglia and a dysfunction in the limbic system. They also point to a complex
      interaction between cortical motor areas, the anterior cingulum, prefrontal
      regions and the basal ganglia.

PMID- 22161168
TI  - [Current treatment strategies for Parkinson's disease].

PMID- 22161170
TI  - Acarbose improves hypoglycaemia following gastric bypass surgery without
      increasing glucagon-like peptide 1 levels.
AB  - BACKGROUND: Postprandial hypoglycaemia is a severe complication of Roux-en-Y
      gastric bypass (RYGBP). Acarbose, an alpha-glucosidase inhibitor (AGI), is
      employed in its treatment. Several studies have shown that AGIs increase the
      postprandial levels of glucagon-like peptide 1 (GLP-1). However, an excessive
      level of GLP-1 is one of the factors involved in the physiopathology of this
      condition. We analysed the effect of acarbose oral administration in eight RYBGP
      patients with clinically significant hypoglycaemia or dumping syndrome. METHODS:
      Glucose, insulin and GLP-1 plasma levels in fasting and after ingestion of a
      standard meal (Ensure Plus(r); 13 g protein, 50 g carbohydrate, 11 g fat) were
      measured. The test was repeated the following week with the oral administration
      of 100 mg of acarbose 15 min prior to the meal. RESULTS: Five patients developed
      asymptomatic hypoglycaemia during the test (glucose level <50 mg/dl) with
      inappropriately high insulin levels and exaggerated GLP-1 response. Acarbose
      ingestion avoided hypoglycaemia in all of the patients and increased the lowest
      plasma glucose level (46.4 +/- 4.8 vs. 59.0 +/- 2.6 mg/dl, p < 0.01). Acarbose
      ingestion decreased the area under the curve for serum insulin and GLP-1 levels
      at 15 min after the meal. CONCLUSIONS: Acarbose avoided postprandial
      hypoglycaemia following RYGBP by decreasing the hyperinsulinemic response. This
      was associated with a decrease in early GLP-1 secretion, in contrast to that
      observed in non-surgical subjects. This finding could be explained by the
      reduction of glucose load in the jejunum produced by the alpha-glucosidase
      inhibition, which is the main stimulus for GLP-1 secretion.

PMID- 22161208
TI  - The role of stimulus type in list length effects in recognition memory.
AB  - While many studies have investigated the list length effect in recognition
      memory, few have done so with stimuli other than words. This article presents the
      results of four list length experiments that involved word pairs, faces,
      fractals, and photographs of scenes as the stimuli. A significant list length
      effect was identified when faces and fractals were the stimuli, but the effect
      was nonsignificant when the stimuli were word pairs or photographs of scenes.
      These findings suggest that the intrastimulus similarity is what dictates whether
      list length has a significant effect on recognition performance. As is the case
      with words, word pairs and photographs of scenes are not sufficiently similar to
      generate detectable item interference.

PMID- 22161209
TI  - Making related errors facilitates learning, but learners do not know it.
AB  - Producing an error, so long as it is followed by corrective feedback, has been
      shown to result in better retention of the correct answers than does simply
      studying the correct answers from the outset. The reasons for this surprising
      finding, however, have not been investigated. Our hypothesis was that the effect
      might occur only when the errors produced were related to the targeted correct
      response. In Experiment 1, participants studied either related or unrelated word
      pairs, manipulated between participants. Participants either were given the cue
      and target to study for 5 or 10 s or generated an error in response to the cue
      for the first 5 s before receiving the correct answer for the final 5 s. When the
      cues and targets were related, error-generation led to the highest correct
      retention. However, consistent with the hypothesis, no benefit was derived from
      generating an error when the cue and target were unrelated. Latent semantic
      analysis revealed that the errors generated in the related condition were related
      to the target, whereas they were not related to the target in the unrelated
      condition. Experiment 2 replicated these findings in a within-participants
      design. We found, additionally, that people did not know that generating an error
      enhanced memory, even after they had just completed the task that produced
      substantial benefits.

PMID- 22161211
TI  - Fermentation of reactive-membrane-extracted and ammonium-hydroxide-conditioned
      dilute-acid-pretreated corn stover.
AB  - Acid-pretreated biomass contains various compounds (acetic acid, etc.) that are
      inhibitory to fermentative microorganisms. Removing or deactivating these
      compounds using detoxification methods such as overliming or ammonium hydroxide
      conditioning (AHC) improves sugar-to-ethanol yields. In this study, we treated
      the liquor fraction of dilute-acid-pretreated corn stover using AHC and a new
      reactive membrane extraction technique, both separately and in combination, and
      then the sugars in the treated liquors were fermented to ethanol with the glucose
      xylose-fermenting bacterium, Zymomonas mobilis 8b. We performed reactive
      extraction with mixtures of octanol/Alamine 336 or oleyl alcohol/Alamine 336. The
      best ethanol yields and rates were achieved for oleyl alcohol-extracted
      hydrolysates followed by AHC hydrolysates, while octanol-extracted hydrolysates
      were unfermentable because highly toxic octanol was found in the hydrolysate.
      Adding olive oil significantly improved yields for octanol-extracted hydrolysate.
      Additional work is underway to determine if this technology is a cost-effective
      alternative to traditional hydrolysate conditioning processes.

PMID- 22161212
TI  - Recycling of cellulosic fibers by enzymatic process.
AB  - In this research, enzymatic treatment as an environmental friendly process has
      been used for recycling process of old cellulosic wastes such as cotton, viscose,
      and lyocell. Cellulase hydrolyses cellulosic chains and shortens cellulosic
      fibers. This study investigates to detect the optimum enzyme concentration and
      time of treatments for suitable changes of length and weight loss. The main
      purposes of this article are shortening of cellulosic fibers and evaluating of
      enzymatic treatment in different kind of cellulosic fibers. According to the data
      of experiments, with the increase of enzyme concentration and the treatment time,
      the length and weight loss percentage of the cellulosic fibers has been
      decreased. The length and weight loss percentage of treated viscose is more than
      that of lyocell and cotton fibers. Optimized condition, reaction time, and enzyme
      concentration have been determined by mean length of treated cellulosic samples.
      Suitable longitudinal distribution of fiber for papermaking industries is in the
      range of 0 to 4 mm. Optimum enzyme concentration and treatment time for recycling
      cotton, lyocell, and viscose fibers are 2% and 48 h for cotton and lyocell and
      0.5% and 48 h for viscose, respectively. According to the data of experiment, the
      length of treated fibers is appropriate for its usage as a raw material in
      papermaking industries.

PMID- 22161213
TI  - Improvement of ethanol yield from glycerol via conversion of pyruvate to ethanol
      in metabolically engineered Saccharomyces cerevisiae.
AB  - The conversion of low-priced glycerol to higher value products has been proposed
      as a way to improve the economic viability of the biofuels industry. In a
      previous study, the conversion of glycerol to ethanol in a metabolically
      engineered strain of Saccharomyces cerevisiae was accomplished by minimizing the
      synthesis of glycerol, the main by-product in ethanol fermentation processing. To
      further improve ethanol production, overexpression of the native genes involved
      in conversion of pyruvate to ethanol in S. cerevisiae was successfully
      accomplished. The overexpression of an alcohol dehydrogenase (adh1) and a
      pyruvate decarboxylase (pdc1) caused an increase in growth rate and glycerol
      consumption under fermentative conditions, which led to a slight increase of the
      final ethanol yield. The overall expression of the adh1 and pdc1 genes in the
      modified strains, combined with the lack of the fps1 and gpd2 genes, resulted in
      a 1.4-fold increase (about 5.4 g/L ethanol produced) in fps1Deltagpd2Delta
      (pGcyaDak, pGupCas) (about 4.0 g/L ethanol produced). In summary, it is possible
      to improve the ethanol yield by overexpression of the genes involved in the
      conversion of pyruvate to ethanol in engineered S. cerevisiae using glycerol as
      substrate.

PMID- 22161214
TI  - In vitro reduction of hexavalent chromium by cytoplasmic fractions of
      Pannonibacter phragmitetus LSSE-09 under aerobic and anaerobic conditions.
AB  - Hexavalent chromate reductase was characterized and was found to be localized in
      the cytoplasmic fraction of a chromium-resistant bacterium Pannonibacter
      phragmitetus LSSE-09. The Cr(VI) reductase activity of cell-free extract (S12)
      was significantly improved by external electron donors, such as NADH, glucose,
      acetate, formate, citrate, pyruvate, and lactate. The reductase activity was
      optimal at pH 7.0 with NADH as the electron donor. The aerobic and anaerobic
      Cr(VI)-reduction enhanced by 0.1 mM NADH were respectively 3.5 and 3.4 times as
      high as that without adding NADH. The Cr(VI) reductase activity was inhibited by
      Mn2+, Cd2+, Fe3+, and Hg2+, whereas Cu2+ enhanced the chromate reductase activity
      by 29% aerobically and 33% anaerobically. The aerobic and anaerobic specific
      Michaelis-Menten constant K(m) of S12 fraction was estimated to be 64.95 and
      47.65 MUmol L-1, respectively. The soluble S150 fractions showed similar activity
      to S12 and could reduce 39.7% and 53.4% of Cr(VI) after 1 h of incubation
      aerobically and anaerobically while the periplasmic contents showed no obvious
      reduction activity, suggesting an effective enzymatic mechanism of Cr(VI)
      reduction in the cytoplasmic fractions of the bacterium. Results suggest that the
      enzymatic reduction of Cr(VI) could be useful for Cr(VI) detoxification in
      wastewater.

PMID- 22161215
TI  - Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in
      early gastric cancer.
AB  - Although minimal invasive treatment is widely accepted in the early stages of
      gastric cancer (GCa), we still do not have any appropriate risk markers to detect
      residual neoplasia and the potential for recurrence. We previously reported that
      aberrant DNA methylation is an early and frequent process in gastric
      carcinogenesis and could be useful for the detection of gastric neoplasia. Our
      goal is to find and identify some candidate genes, using genome-wide DNA
      methylation analysis, as a treatment marker for early gastric cancer (EGC). We
      performed methylated CpG island amplification microarray analysis using 12
      gastric washes (six each of pre- and post-endoscopic treatment in each of the
      same patients). We finally focused on Sox17 gene. We examined the DNA methylation
      status of Sox17 in a validation set consisting of 128 wash samples (pre, 64;
      post, 64) at EGC. We next carried out functional studies to identify Sox17. Sox17
      showed significant differential methylation between pre- and post-treatments in
      EGC patients (Sox17, p < 0.0001). Moreover, treating GCa cells that lacked Sox17
      expression with a methyltransferase inhibitor, 5-aza-2'-deoxycytidine, restored
      the gene's expression. Additionally, the introduction of exogenous Sox17 into
      silenced cells suppressed colony formation. Gastric wash-based DNA methylation
      analysis could be useful for early detection of recurrence following endoscopic
      resection in EGC patients. Our data suggest that the silencing of Sox17 occurs
      frequently in EGC and may play a key role in the development and progression of
      the disease.

PMID- 22161216
TI  - Lentivirus-mediated siRNA interference targeting SGO-1 inhibits human NSCLC cell
      growth.
AB  - Aneuploid is recognized as a hallmark of cancer and is caused by chromosome mis
      segregation during mitosis. Recent studies have identified shugoshin (SGO-1) as
      an important player in proper chromosome segregation and the involvement in
      tumorigenesis. But, little is known about how SGO-1 is involved. The aim of this
      study was to obtain information about the role of SGO-1 in human lung cancer
      cells. In our study, real-time PCR and western blotting assay were performed to
      detect the expression of SGO-1 in nonsmall cell lung cancer (NSCLC) cell lines.
      Then, we successfully constructed a lentivirus vector mediating RNAi targeting of
      SGO-1 (LV-SGO-1 siRNA) and proved that it can suppress the expression of SGO-1
      gene in H1299 cells. We found that SGO-1 was highly expressed in NSCLC cancer
      cell lines. RNA interference of SGO-1 by the LV-SGO-1 siRNA construct
      significantly decreased SGO-1 protein expression and inhibited the growth and
      ability of forming colonies of H1299 cells with more cells arrested in G2/M
      phase, but lentivirus vector control had no effect on H1299 cells. Moreover,
      suppression of SGO-1 by LV-SGO-1 siRNA increased the apoptosis of H1299 cells
      with down-regulated Bcl-2 and up-regulated Bax. SGO-1 may provide a novel
      therapeutic target for the treatment of lung cancer since it inhibits the growth
      and increases the apoptosis of lung cancer cells.

PMID- 22161217
TI  - Identification of furo[3', 2':3,4]naphtho[1,2-d]imidazole derivatives as orally
      active and selective inhibitors of microsomal prostaglandin E(2) synthase-1
      (mPGES-1).
AB  - This study describes the synthesis and anti-inflammatory effects of furo[3',
      2':3,4]naphtho[1,2-d] imidazole derivatives. Among these furo[3',
      2':3,4]naphtho[1,2-d]imidazole derivatives, 2-(4-methoxyphenyl)furo [3',
      2':3,4]naphtho[1,2-d]imidazole (12) exhibited a strong inhibitory activity
      against LPS-induced PGE(2) production, with an IC(50) value of 47 nM. Compound 12
      is then further examined for its inhibitory effects in the protein expression of
      COX-2 and microsomal prostaglandin E(2) synthase-1 (mPGES-1) in Raw 264.7 cells.
      Our results indicate that compound 12 was capable against inhibiting LPS-induced
      mPGES-1 protein expression at a concentration of 1.0 MUM and no inhibitory effect
      in COX-2 expression. The sepsis-induced PGE(2) production in rat serum decreased
      ~250% by the pretreatment of 12 at 10 mg/kg. These results are especially
      important since compound 12 exhibited good oral bioavailability (72%) and was not
      cytotoxic at a concentration of 10.0 MUM. Therefore, compound 12 is a highly
      selective mPGES-1 inhibitor that can serve as a lead for the development of novel
      oral anti-inflammatory drug candidates.

PMID- 22161219
TI  - Predictors of hearing protection behavior among firefighters in the United
      States.
AB  - BACKGROUND: Noise-induced hearing loss (NIHL) is a major occupational health
      problem that can be prevented through the use of hearing protection devices
      (HPDs). PURPOSE: The purpose of this study is to identify significant factors
      related to firefighters' use of HPDs. METHODS: A total of 404 firefighters from
      35 fire departments in multiple states in the United States participated in an
      Internet-based survey from March 2010 to May 2011. RESULTS: Pearson correlations
      and multiple regression analysis suggested that several modifying and cognitive
      perceptual factors were significantly related to HPD use, including noise
      exposure, interpersonal influences, organizational support, perceived barriers to
      HPD use, and perceived susceptibility to hearing loss. The multiple regression
      model explained 56% (R(2) = .56, adjusted R(2) = .54) of the variance in
      firefighters' use of HPDs (F(13, 372) = 35.65, p < .001). CONCLUSIONS: Future
      research should focus on incorporating these significant predictors into
      effective behavioral interventions designed to promote the use of HPDs in this
      population.

PMID- 22161220
TI  - Life changes in patients after out-of-hospital cardiac arrest : the effect of
      near-death experiences.
AB  - BACKGROUND: Cardiac arrest is a traumatic event that often affects patients'
      lives in many ways. Patients after near-death experiences (NDEs) often express
      strong and permanent change of their values, beliefs and principles. PURPOSE: The
      aim of this study was to determine the association between NDEs and life changes
      in patients 6 months after out-of-hospital cardiac arrest. METHOD: This was a
      prospective observational study, which included 37 patients (average age 54.0
      years, range 22-81 years, 29 males) 6 months after out-of-hospital cardiac
      arrest. The presence of NDEs was assessed with a self-administered Greyson's NDE
      scale. The intensity of life changes was assessed with a self-administered Ring's
      life change inventory. Univariate analysis was performed. RESULTS: NDEs were
      reported by seven (18.9%) patients. In comparison to the non-NDEs group, patients
      in the NDEs group expressed significantly stronger changes in the following
      items: tolerance for others, understanding of myself, appreciation of nature,
      sense that there is some inner meaning to my life and concern with questions of
      social justice. CONCLUSIONS: Cardiac arrest survivors do not express extensive
      life changes. But, the presence of NDEs is significantly associated with the
      change of interest in some aspects of patients' lives. Such patients should be
      prepared for significant life changes that might occur after NDEs by health
      workers and receive professional help to accommodate to them.

PMID- 22161218
TI  - Mendelian randomization: application to cardiovascular disease.
AB  - In the absence of an ethical, practical, and economical randomized trial, the
      epidemiologist is left to explore other methods in efforts to assert causality.
      An approach based on genotypic variation has the potential to mitigate against
      some of the problems found within conventional observational studies. Genetic
      variations associated with risk factors of interest at the population level can
      be used as proxy measures for these risk factors and to generate estimates of
      causal effect. The potential and the possible limitations of this approach within
      the cardiovascular field are presented in this review.

PMID- 22161221
TI  - BioDMET: a physiologically based pharmacokinetic simulation tool for assessing
      proposed solutions to complex biological problems.
AB  - We developed a detailed, whole-body physiologically based pharmacokinetic (PBPK)
      modeling tool for calculating the distribution of pharmaceutical agents in the
      various tissues and organs of a human or animal as a function of time. Ordinary
      differential equations (ODEs) represent the circulation of body fluids through
      organs and tissues at the macroscopic level, and the biological transport
      mechanisms and biotransformations within cells and their organelles at the
      molecular scale. Each major organ in the body is modeled as composed of one or
      more tissues. Tissues are made up of cells and fluid spaces. The model accounts
      for the circulation of arterial and venous blood as well as lymph. Since its
      development was fueled by the need to accurately predict the pharmacokinetic
      properties of imaging agents, BioDMET is more complex than most PBPK models. The
      anatomical details of the model are important for the imaging simulation
      endpoints. Model complexity has also been crucial for quickly adapting the tool
      to different problems without the need to generate a new model for every problem.
      When simpler models are preferred, the non-critical compartments can be
      dynamically collapsed to reduce unnecessary complexity. BioDMET has been used for
      imaging feasibility calculations in oncology, neurology, cardiology, and
      diabetes. For this purpose, the time concentration data generated by the model is
      inputted into a physics-based image simulator to establish imageability criteria.
      These are then used to define agent and physiology property ranges required for
      successful imaging. BioDMET has lately been adapted to aid the development of
      antimicrobial therapeutics. Given a range of built-in features and its inherent
      flexibility to customization, the model can be used to study a variety of
      pharmacokinetic and pharmacodynamic problems such as the effects of inter
      individual differences and disease-states on drug pharmacokinetics and
      pharmacodynamics, dosing optimization, and inter-species scaling. While
      developing a tool to aid imaging agent and drug development, we aimed at
      accelerating the acceptance and broad use of PBPK modeling by providing a free
      mechanistic PBPK software that is user friendly, easy to adapt to a wide range of
      problems even by non-programmers, provided with ready-to-use parameterized models
      and benchmarking data collected from the peer-reviewed literature.

PMID- 22161222
TI  - Design of pharmacokinetic studies for latent covariates.
AB  - Latent covariates are covariates that are known to exist but are either
      observable but unavailable or unobservable at the time of the clinical study.
      Designs to account for latent covariates must incorporate both uncertainty in the
      prevalence of the covariate and the data-type of the covariate. The
      informativeness of the covariate will then depend on whether the covariate data
      is continuous, ordinal or nominal. In this work we consider designs for latent
      covariates that may either directly influence the parameter of interest, or
      indirectly via actions on an observable covariate which then influences the
      parameter of interest. We consider a motivating example based on the effect of a
      genetic polymorphism on the influence of a continuous covariate (age) on drug
      clearance (CL). The polymorphism could take the case of a haplotype with many
      variant alleles, or a copy number variation in genes with different phenotypic
      expressions which could be treated as continuous data, or as a bi- or tri-allelic
      single nucleotide polymorphism that could form either an ordinal or nominal
      covariate on drug CL. The aim of this study was to investigate designs for
      clinical studies for latent covariates that accommodate both unknown prevalence
      and unknown data-type. Initially, the informativeness of a covariate was explored
      using linear regression assuming the three data-types continuous, ordinal and
      nominal. The linear covariate model was then considered within a nonlinear mixed
      effects modelling framework. Two simulation scenarios were considered: (1) the
      influence of the latent covariate directly on the parameter of interest and (2)
      the influence of the latent covariate on an observable non-latent continuous
      covariate, which was assumed to follow a normal or stratified distribution, and
      the effect of this covariate on the parameter of interest. A power analysis for
      population PK modelling (1) where the latent covariate had direct influence on
      the parameter also showed similar behaviour to the linear regression solution.
      When the influence of the latent covariate was mediated via another observable
      non-latent continuous covariate, the power for the continuous model was highest
      but the power of the ordinal model was indistinguishable from that of the nominal
      model. Stratification of the observable non-latent continuous covariate did not
      appreciably change the power to identify the latent covariate from that when we
      assumed the observable covariate conformed to a normal distribution. It was found
      that parameter estimation is generally at least 1.5 to 7 fold more precise for
      continuous models than for categorical models.

PMID- 22161223
TI  - Interspecific differences in tannin intakes of forest-dwelling rodents in the
      wild revealed by a new method using fecal proline content.
AB  - Mammalian herbivores adopt various countermeasures against dietary tannins, which
      are among the most widespread plant secondary metabolites. The large Japanese
      wood mouse Apodemus speciosus produces proline-rich salivary tannin-binding
      proteins in response to tannins. Proline-rich proteins (PRPs) react with tannins
      to form stable complexes that are excreted in the feces. Here, we developed a new
      method for estimating the tannin intake of free-living small rodents, by
      measuring fecal proline content, and applied the method to a field investigation.
      A feeding experiment with artificial diets containing various levels of tannic
      acid revealed that fecal proline content was clearly related to dietary tannin
      content in three species (A. speciosus, Apodemus argenteus, and Myodes
      rufocanus). We then used fecal proline content to estimate the tannin intakes of
      these three forest-dwelling species in a forest in Hokkaido. In the autumn,
      estimated tannin intakes increased significantly in the Apodemus species, but not
      in M. rufocanus. We speculated that an increase in tannin intake during autumn
      may result from consumption of tannin-rich acorns. This hypothesis was consistent
      with population fluctuation patterns of the three species, which were well
      synchronized with acorn abundance for the Apodemus species but not for M.
      rufocanus.

PMID- 22161224
TI  - The scent of a partner: ambrosia beetles are attracted to volatiles from their
      fungal symbionts.
AB  - Invasive fungus-growing ambrosia beetles are an emerging threat to forest
      ecosystems and fruit industries, but management tools are lacking. Here we
      explored the potential of beetle symbionts-ambrosia fungi-as a source of
      attractants. Our focus was the redbay ambrosia beetle, Xyleborus glabratus, and
      its symbiotic fungus, Raffaelea lauricola, which are devastating lauraceous hosts
      in the southeastern United States. We also tested three additional co-occurring
      beetle species and their symbionts. Each beetle species was consistently
      attracted to the odors of its symbiotic fungal species, occasionally also to
      symbionts of other species, but never to non-symbiotic Trichoderma. We further
      confirmed attraction to ethanol (positive control) in some species. Thus,
      ambrosia fungi produce volatiles attractive to their vector beetles, which may
      have potential as novel lures for ambrosia beetle management.

PMID- 22161226
TI  - Attainment of 15-fold higher affinity of a Fusarium-specific single-chain
      antibody by directed molecular evolution coupled to phage display.
AB  - Fusarium head blight (FHB) caused by Fusarium graminearum infection is a
      devastating disease of wheat, maize, and other cereals. A previously isolated
      chicken single-chain Fv antibody (scFv), CWP2, that conferred durable resistance
      in planta was subjected to directed evolution by error-prone PCR and DNA
      shuffling, generating a mutated library. Panning of the mutated library against
      cell wall-bound proteins (CWPs) from F. graminearum by phage display enriched
      phage clones that were used for a further round of DNA shuffling to construct a
      combinatorial library comprising 3 * 10(6) variants. Screening of this library by
      phage display for variants reactive against the CWPs led to the identification of
      a number of clones. Comparative enzyme-linked immunosorbent assay analyses
      revealed eight clones exhibiting a higher reactivity than the parent, CWP2, and
      containing four different single-chain antibody sequences. Surface plasmon
      resonance measurements confirmed that three mutated scFvs, CWPa, CWPb, and CWPd,
      displayed 15-fold, 11-fold, and 7-fold higher affinities, respectively, compared
      with CWP2. Three-dimension modeling of CWPa illustrates a conformational change
      bringing all six complementary domain regions on the antibody surface in one
      direction. These results provide promising unique resistance molecules for
      effective control of FHB and its associated mycotoxins in food/feed chains.

PMID- 22161227
TI  - [Pharmacotherapy for anorexia nervosa and bulimia nervosa].
AB  - Psychotherapy is the treatment of choice for both anorexia nervosa and for
      bulimia nervosa. However, many patients are also treated by pharmaceutical drugs.
      For the clinician it is difficult to choose pharmacotherapy, because the drugs
      may not be licensed, because of pharmacodynamic problems due to underweight or
      purging behaviour, or because of comorbidity. The present review summarises the
      current knowledge on pharmacotherapy for anorexia nervosa and bulimia nervosa
      considering the available guidelines. In general, the knowledge based on studies
      is insufficient for anorexia nervosa. Up to now, there is no proof of efficacy
      for any antidepressant or atypical antipsychotic with respect to weight gain;
      atypical antipsychotics may be helpful for ruminating or excessive motor
      hyperactivity. For bulimia nervosa antidepressants are the pharmacotherapy of
      first choice. Long-term effects, however, are still unknown.

PMID- 22161228
TI  - [Use of amino acid PET in the Diagnostic and Treatment Management of cerebral
      gliomas].
AB  - Structural as well as functional imaging methods are of special importance in
      neurooncology. Improvements of radionuclide and magnetic resonance-based imaging
      modalities over the past decade have enabled clinicians to non-invasively assess
      the dynamics of disease-specific processes at the molecular level in patients
      with malignant gliomas. To date, a range of complementary imaging parameters have
      been established in the diagnostic work-up of patients with brain tumours.
      Magnetic resonance imaging (MRI) provides morphological information as well as
      functional information such as vascular permeability, cell density, tumour
      perfusion, and metabolic information by using magnetic resonance spectroscopy.
      The use of radiolabelled amino acids for positron emission tomography (PET)
      allows a better delineation of tumour margins and improves targeting of biopsy
      and radiotherapy, and planning surgery. In addition, amino acid imaging appears
      useful in distinguishing tumour recurrence from non-specific post-therapeutic
      scar tissue, in predicting prognosis in low-grade gliomas, and in monitoring
      metabolic response during treatment. Taken together, MRI and PET provide
      complementary information about tumour biology and activity, thereby resulting in
      an improved understanding of the kinetics of tumour growth and therefore allow
      new insights into the pathophysiology of malignant brain tumours. However,
      multimodal imaging studies comparing the value of amino acid PET and functional
      methods of MRI (e. g., perfusion and diffusion weighted imaging) are needed. From
      these studies, surrogate MRI and PET imaging techniques need to be derived to
      gain complementary structural and functional information of brain tumours that
      can be placed into common clinical practice which will optimise the clinical
      management of patients with malignant gliomas.

PMID- 22161225
TI  - Modern trends into the epidemiology and screening of ovarian cancer. Genetic
      substrate of the sporadic form.
AB  - Ovarian cancer (OC) is a heterogeneous disease, including a broad spectrum of
      histological subtypes and demonstrating diverse biological behavior. Epithelial
      derived ovarian malignant tumours constitute the predominant and most lethal form
      of the disease. Age, genetic predisposition, gynecological and reproductive
      factors and environmental factors are the main risk factors that increase the
      risk for acquiring OC. Vaginal examination, ultrasonography and measurement of
      blood serum levels of tumour markers, especially CA125 constitute the first-line
      screening modalities for OC, whereas second-line testing involves more accurate
      imaging techniques such as color Doppler ultrasound of the lesion or/and a CT
      scan. Sex steroid hormone pathway genes, cell cycle genes, DNA repair genes,
      oncogenes and onco-suppressor genes have been associated with a genetic
      susceptibility to sporadic OC. In the present review we focus on the major
      oncogenes and onco-suppressor genes in the sporadic form of the disease. Each
      tumour subtype is associated with a unique molecular signature, as revealed by
      current genetic and biomarker profiling studies. Different OC pathways emerge
      early in the process of carcinogenesis, ultimately leading to clinically
      different tumour types. As mutations acquired early during tumourigenesis will be
      present in all later stages, large-scale gene expression profiling using DNA
      microarray analysis techniques can help to classify ovarian cancers into
      clinically relevant subtypes.

PMID- 22161229
TI  - [Post-traumatic and psychotic symptoms in severely traumatised patients].
AB  - BACKGROUND: Severely traumatised patients may show a variety of impairments,
      including psychotic symptoms. The therapist's specific professional background
      (e. g., trauma-focussed psychotherapy or general psychiatry) may impede adequate
      diagnosis and treatment of these patients. METHODS: Three case reports show the
      development and change of post-traumatic and psychotic symptoms over time and the
      influence of specific interventions. CONCLUSIONS: It is important not to jump to
      conclusions and interpret perceptual disturbances (flashbacks, dissociative or
      psychotic ones) too quickly in an one-sided way. Further scientific
      investigations are mandatory in order to understand and treat patients in an
      adequate way.

PMID- 22161230
TI  - [Expert opinions in German statutory accident insurance].
AB  - German statutory accident insurance covers employees and trainees against
      occupational accidents, employers bear the inherent charges. Expert opinion is
      obtained, in particular, for discussing causality questions and for rating
      accidental health disorders. Causality has to be estimated based on the "theory
      of essential condition", health disorders have to be substantiated without any
      reasonable doubt. Reduction in earning capacity due to an accident may not
      consider the individual kind of occupation and has to be rated by an abstract
      approach.

PMID- 22161231
TI  - Ten years experience of banded gastric bypass: does it make a difference?
AB  - Many surgeons support some sort of restriction of the gastric pouch outlet by
      placing a ring around the gastric reservoir. Previous studies have shown positive
      results of banded gastric bypass (BGBP); however, there are not many comparative
      long-term studies to assess the real advantage of placing a ring during gastric
      bypass (GBP) surgery. This study aims to evaluate the long-term outcome of
      patients subjected to BGBP and nonbanded GBP procedures. We studied 260
      retrospective, nonrandomized obese patients who underwent BGBP and 218 patients
      without the ring (i.e., GBP). They were followed up for 10 years, and the
      following parameters were evaluated: excess weight loss (EWL), quality of life
      (QOL), food tolerance, and correction of comorbidities. The study was approved by
      the Committee on Ethics, and all the patients gave their informed consent. There
      is a significant difference in %EWL from the third year until the tenth year of
      observation, with the proportion being 82% in BGBP versus 63% in nonbanded GBP
      patients at the end of the study. Although there was some increased intolerance
      to food intake in the BGBP patients, this was not felt to reduce the QOL. The
      outcome in terms of comorbidities was not conclusive. There is a clear advantage
      in terms of %EWL in the BGBP patients. No differences in QOL were found in both
      groups. Further, selecting the right type of material and the right size of the
      ring is important to improve results and avoid complications.

PMID- 22161232
TI  - The value of an employment-based green card.
AB  - The need for and role of highly skilled immigrant workers in the U.S. economy is
      fiercely debated. Proponents and opponents agree that temporary foreign workers
      are paid a lower wage than are natives. This lower wage partly originates from
      the restricted mobility of workers while on a temporary visa. In this article, we
      estimate the wage gain to employment-based immigrants from acquiring permanent
      U.S. residency. We use data from the New Immigrant Survey (2003) and implement a
      difference-in-difference propensity score matching estimator. We find that for
      employer-sponsored immigrants, the acquisition of a green card leads to an annual
      wage gain of about $11,860.

PMID- 22161233
TI  - [Structure and process quality of quality-assured mamma diagnostics in Schleswig
      Holstein].
AB  - PURPOSE: To demonstrate the structure and process quality of quality-assured
      mamma diagnostics (QuaMaDi) by means of quality indicators as defined in the
      European Guidelines for Quality Assurance in Breast Cancer Screening and
      Diagnosis and in the National Guideline on Early Detection of Cancer in Germany.
      Furthermore, spatial differences and changes in the chronological sequence were
      analyzed. MATERIALS AND METHODS: We used administrative data as documented in the
      time period 2006 - 2009 in QuaMaDi in Schleswig-Holstein (SH), Germany, and
      analyzed quality indicators as defined in the abovementioned guidelines (absolute
      and relative frequencies, 95 % confidence intervals). RESULTS: Each year
      approximately 6 % of all women age 20 or older living in SH are examined using
      QuaMaDi. Only minor differences regarding age and clinical data were seen between
      the patients in the four regions of SH. Reference values for the quality
      indicators are largely reached (i. e., proportion of women with breast density
      ACR 3 or 4 plus additional ultrasound = 96.2 %; proportion with repeated
      mammography = 0.2 %). Spatial differences are only minor. In the chronological
      sequence, quality indicators improve, if they did not reach the reference values
      in the beginning, or indicate a high and constant quality. CONCLUSION: With
      regard to those quality indicators that were computable, reference values as
      defined in the guidelines were reached in 9 of 12 cases. In one case the
      difference between the observed value and the reference values is system-immanent
      and in another case the difference is less than four percentage points (reference
      value 90 %).

PMID- 22161234
TI  - [Change in health-related quality of life and change in clinical symptoms after
      uterine artery embolization in patients with symptomatic adenomyosis uteri -
      evaluation using a standardized questionnaire].
AB  - AIM: To evaluate the clinical response of uterine artery embolization (UAE) in
      women with symptomatic uterine adenomyosis by comparing health-related quality of
      life and symptom severity before and after UAE using a standardized
      questionnaire. MATERIAL AND METHODS: This longitudinal study at two time points
      included 17 patients with a median age of 47.1 years with symptomatic uterine
      adenomyosis (n = 7 pure adenomyosis; n = 10 with concomitant fibroids). The
      diagnosis was based on clinical symptoms and magnetic resonance imaging (MRI)
      criteria. Data on health-related quality of life and severity of symptoms before
      and after UAE were obtained by the standardized "Uterine Fibroid Symptom and
      Quality of Life" (UFS-QOL) questionnaire and correlated in the following.
      Treatment failure was defined as the need for a second invasive procedure because
      of recurrent symptoms or persistent symptoms after UAE. RESULTS: The median
      interval between the evaluation of the UFS-QOL questionnaire before and after UAE
      was 46.0 months. 70.6 % (12/17; 95 % confidence interval 44.0 %  - 88.6 %) of the
      patients had therapy response with a significant improvement of health-related
      quality of life and clinical symptoms (p-value = 0.002). The therapy failure rate
      was 29.4 % (5/17; 95 % confidence interval 11.4 %  - 56.0 %). One patient
      underwent dilatation and curettage and four patients underwent hysterectomy
      because of therapy failure. CONCLUSION: UAE to treat symptomatic adenomyosis
      uteri can significantly improve the health-related quality of life and clinical
      symptoms. However, therapy failure is possible in up to one-third of patients.

PMID- 22161235
TI  - [Assessment of patient movement in interventional procedures using
      electromagnetic detection - comparison between conventional fixation and vacuum
      mattress].
AB  - PURPOSE: To assess patient movement on a vacuum mattress compared to a standard
      viscoelastic mattress during interventional procedures using an electromagnetic
      tracking device. MATERIALS AND METHODS: In 17 consecutive patients who underwent
      a diagnostic or interventional procedure, the patient was positioned using a
      vacuum mattress (VL, n = 9) or a standard viscoelastic mattress (SL, n = 8). The
      patient position was recorded continuously after the start of the procedure (S)
      using an electromagnetic navigation device. After the intervention (E), patients
      were asked to lift up the upper part of the body and to lie down again
      (repositioning maneuver, P). Based on the recorded patient positions, the patient
      movement (PM) at rest DeltaP(SE), PM due to the repositioning maneuver
      DeltaP(EP), total PM DeltaP(SP) and maximum PM during the intervention
      DeltaPMax(SE) were calculated. RESULTS: Using VL, PM at rest (DeltaP[SE]: VL: 4.3
      +/- 2.8 mm, SL: 17.1 +/- 15.7 mm; p = 0.036) and total PM (DeltaP[SP]: VL: 4.6 mm
      +/- 2.5 +/- mm, SL: 27.8 +/- 19.6 mm; p = 0.002) were significantly smaller. In
      contrast, the maximum PM as a parameter for the mobility of the patient
      (DeltaPMax(SE): VL: 14.2 +/- 15.1 mm, SL: 17.6 +/- 13.4 mm; p = 0.48) and the PM
      due to the repositioning maneuver (DeltaP[EP]: VL: 4.4 +/- 2.5 mm, SL: 15.7 mm +/
      15.9 mm, p = 0.32) were similar. CONCLUSION: Patient positioning on a vacuum
      mattress is fast, easy, comfortable for the patient and reduces relevant patient
      movements. Therefore, vacuum mattress positioning can be used for image-guided
      interventions relying on preprocedural imaging data, where minimal patient
      movement is a prerequisite.

PMID- 22161236
TI  - [Peripartal sacrum fracture - a rare cause of peripartal lumbar sciatica].

PMID- 22161237
TI  - Utility of serum tumor markers as an aid in the differential diagnosis of
      patients with clinical suspicion of cancer and in patients with cancer of unknown
      primary site.
AB  - Cancer may be diagnosed in advanced stages, when the patient has already
      developed metastasis, with symptoms that can be also observed in benign diseases.
      The objective of this study was to evaluate tumor marker sensitivity and
      specificity in the differential diagnosis of patients with suspected signs of
      cancer. We studied 2.711 consecutive patients admitted to the Internal Medicine
      Department of our hospital with suspected cancer; 1.240 patients had non
      malignant processes and 1.471 had malignant disease. Determinations were
      considered positive for suspected malignancy when serum levels were
      carcinoembryonic antigen >15 ng/ml (>20 in patients with renal failure or liver
      disease), alpha fetoprotein >40 ng/ml (>80 ng/ml in patients with liver
      diseases), carbohydrate antigen (CA) 19.9 > 200 U/ml (>500 U/ml in patients with
      liver diseases or gamma glutamyl transpeptidase (GGT) <150 UI/L or effusions;
      >1.000 U/ml in patients with jaundice or GGT > 150 UI/L), neuron-specific enolase
      >45 ng/ml (renal failure >50 ng/ml; samples with hemolysis were excluded),
      prostate-specific antigen > 30 ng/ml (excluding acute prostatitis), tumor
      associated glycoprotein-72 >80 U/ml, cytokeratin 19 fragment 21-1 > 7.5 ng/ml
      (>19 ng/ml in patients with renal failure; >11 ng/ml in patients with liver
      cirrhosis or jaundice), >3.5 ng/ml for squamous cell carcinoma (excluding
      patients with renal failure or skin disorders), CA 15.3 >100 U/ml, and CA 125
      >350 U/ml (>600 U/ml in patients with pleural effusion and >900 U/ml in those
      with ascites). There was a specificity of 97.6% in patients without malignancy,
      67.4% of sensitivity in patients with malignancy, and 75.4% of sensitivity in the
      1,280 patients with epithelial tumors (53.7% in patients with locally advanced
      tumors and 79.4% in patients with metastases). Sensitivity was 81.4% in patients
      with cancer of unknown primary site. Tumor markers were useful in the
      differential diagnosis between epithelial and non-epithelial tumors, brain masses
      (metastases vs. primary tumors), and between benign or malignant origin of
      different clinical situations such as wasting syndrome, effusions, liver or bone
      lesions, and effusions with a positive predictive value higher than 95%. Tumor
      markers are useful as an aid in the evaluation of the risk of cancer of these
      patients with suspected cancer and may be useful to reduce the hospitalization
      time, morbidity, and the number of diagnostic tests required for diagnosis.

PMID- 22161238
TI  - Lactobacillus plantarum AS1 isolated from south Indian fermented food Kallappam
      suppress 1,2-dimethyl hydrazine (DMH)-induced colorectal cancer in male Wistar
      rats.
AB  - The relationship between antioxidant and anticancer properties of probiotic
      bacterium strain Lactobacillus plantarum AS1 (AS1) in colon cancer induced by 1,2
      dimethylhydrazine (DMH) has been studied. In this study, an increased level of
      lipid peroxide (LPO) products and increased activities of antioxidant enzymes
      (superoxide dismutase, catalase and glutathione-S transferase) and marker enzymes
      (alkaline phosphatase and acid phosphatase) in colon and plasma of cancer-bearing
      animals have been observed. AS1 was supplemented either before initiation or
      during initiation and selection/promotion phases of colon carcinogenesis and was
      found to be effective in altering lipid peroxidation and antioxidant enzyme
      activities and marker enzymes to a statistically significant level measured
      either in the colon and in the plasma. These alterations inclined towards normal
      in a time-dependent manner on AS1 supplementation. The mean tumor volume diameter
      and total number of tumors were found to be statistically decreased in AS1 pre-
      and post-treated rats. Furthermore, histopathological examination shows
      remarkable difference between control and treated groups. The in vitro
      antioxidant assay shows that AS1 has promising antioxidant property. These
      results demonstrate that AS1 strain can modulate the development of DMH-induced
      rat colon carcinogenesis through an antioxidant-dependent mechanism.

PMID- 22161239
TI  - Identification of WA-type three-line hybrid rice with real-time polymerase chain
      reaction (PCR) method.
AB  - A real-time fluorescent PCR (RTF-PCR) was developed to detect and quantify wild
      abortive (WA)-type three-line hybrid rice (Oryza sativa L.). The mitochondrial R2
      630 WA gene was reported to be closely related to male sterility in plants, and
      developed as a molecular maker to identify the cytoplasmic male sterility system
      of hybrid rice. First, we got the DNA sequence of R2-630 WA gene in 17 rice
      species with traditional PCR. Then, a pair of specific primers (P3, P4) and
      TaqMan fluorescence probe (P3-14) were designed based on the R2-630 DNA sequence.
      The following RTF-PCR was performed on the 17 rice species finally. The results
      indicate that the probes used here are specific for three-line hybrid rice F1 and
      male sterile lines. We can even identify a single hybrid seed using the probes,
      which confirmed that the probes can be applied to the identification and
      quantification of the WA-type three-line hybrid rice. In addition, the RFT-PCR
      system can be optimized when the annealing temperature is 60  degrees C and the
      Mg2+ concentration is 3.5 mmol/L.

PMID- 22161240
TI  - Current concept in the pathophysiology of hepatitis delta infection.
AB  - Hepatitis delta virus (HDV) is a unique human virus, showing similarities with
      plant viroids. Although impressive knowledge on virus structure and replication
      has been achieved, several questions like HBV/HDV interaction and post
      translational modifications of HD antigens remain to be answered. Potential
      targets for therapeutic strategies are now emerging. To date, eight major
      genotypes of the HDV have been identified. The HDV-1 is the prevailing genotype
      in Europe, but migration phenomena may change this profile. Immune response is
      likely to play an important role in the pathogenesis of HDV-induced liver
      disease; few data are available on T cells response either during infection and
      therapy. HDV usually suppresses HBV replication; recent studies show as viral
      dominances may change over time. Delta infection leads to severe liver disease,
      with different patterns of progression to liver fibrosis and decompensation.
      Beside the association between HDV/HBV and HCC is demonstrated a risk
      specifically related to HDV remains controversial.

PMID- 22161241
TI  - Review article: new directions in medical education related to anesthesiology and
      perioperative medicine.
AB  - PURPOSE: We aim to provide a broad overview of current key issues in
      anesthesiology education to encourage both "clinician teachers" and "clinician
      educators" in academic health centres to consider how medical educational theory
      can inform their own practice. PRINCIPAL FINDINGS: Evolving contextual issues,
      such as work-hour reform and the patient safety movement, necessitate innovative
      approaches to anesthesiology education. There is a substantial amount of relevant
      literature from other disciplines, such as sociology, psychology, and human
      factors research, using methodologies that are often unfamiliar to most
      clinicians. Recurring themes include the increasing use of simulation-based
      education, the importance of faculty development, challenges in teaching and
      assessing the non-medical expert roles, and the promise of team training and
      interprofessional education. Interdisciplinary collaborations are likely key to
      answering pressing questions in anesthesiology education, and a greater
      understanding of qualitative and mixed methods research will allow a broader
      range of questions to be answered. Simulation offers the opportunity to learn
      from failures without exposing patients to risk and brings the challenge of
      integrating innovations into existing curricula. Interprofessional education
      allows learning in the teams that will work together; even so, it needs to be
      prioritized to overcome logistical barriers. The challenges of introducing a
      competency-based curriculum have resulted in hybrid systems where elements of
      competency-based medical education have been combined with traditional
      apprenticeship curricula. The value of faculty development to encourage even
      simple measures, such as establishing learning objectives and discussing these
      with trainees, cannot be over-emphasized. Key issues in assessment include the
      need to evaluate multiple levels of performance in a cohesive system of
      assessment and the need to identify the unintended consequences of assessment.
      CONCLUSIONS: We have identified a number of key themes and challenges for
      anesthesiology education. This discussion will continue in greater depth in
      individual articles in this issue so as to promote further interest in a growing
      body of literature that is relevant to anesthesiology education.

PMID- 22161243
TI  - Bleeding in a Jehovah's Witness patient undergoing a redo aortic valve
      replacement controlled with cryoprecipitate and a prothrombin complex
      concentrate.
AB  - PURPOSE: This is a case report involving a middle-aged Jehovah's Witness patient
      who underwent a redo aortic valve replacement, coronary artery bypass graft, and
      Maze procedure facilitated by cardiopulmonary bypass. The consent process
      included a discussion of the management of bleeding and hemostasis in the
      perioperative period in the context of the patients' religious choice and the
      possible consequences of avoiding transfusion in massive bleeding. The medical
      team agreed to abide by the patient's wishes with respect to the blood and blood
      products deemed unacceptable by the patient irrespective of the consequences. The
      consent included a discussion of manufactured hemostatic agents that are
      designated by the Hospital Liaison Committee Network for Jehovah's Witnesses as
      subject to personal decision. There was also a discussion of recombinant agents
      available, all of which are acceptable to Jehovah's Witness patients. The patient
      accepted the use of cryoprecipitate, prothrombin complex concentrate, and
      recombinant factor VIIa. CLINICAL FEATURES: After separation from cardiopulmonary
      bypass and protamine administration, blood loss was 350 mL over a ten-minute
      period. The international normalized ratio (INR) was 3.5 at that time.
      Cryoprecipitate 15 U, 1-deamino-8-D-arginine vasopressin 16 U, and a prothrombin
      complex concentrate, Octaplex(r), 60 mL were administered. Blood loss improved
      significantly. The INR in the cardiac surgical intensive care unit was 1.3. The
      sample was taken approximately one hour following the administration of the
      hemostatic agents. The patient's chest was closed, and chest tube drainage was
      310 mL over the next 12 hr. CONCLUSION: This is a novel case involving the use of
      prothrombin complex concentrate in the setting of a Jehovah's Witness patient
      undergoing a complex operative procedure.

PMID- 22161244
TI  - Persistent hypothermia after intrathecal morphine: case report and literature
      review.
AB  - PURPOSE: To describe a case of persistent hypothermia following spinal anesthesia
      with intrathecal morphine. CLINICAL FEATURES: Following elective right total knee
      arthroplasty under spinal anesthesia with isobaric 0.5% bupivacaine 11 mg,
      fentanyl 15 MUg, and preservative-free morphine 150 MUg, a 57-yr-old female (93.5
      kg, 151 cm) developed postoperative hypothermia with a nadir rectal temperature
      of 33.6 degrees C four hours after surgery. At times, her temperature could not
      be measured by tympanic, temporal arterial, oral, axillary, or rectal routes. In
      spite of the low temperature, the patient complained of feeling hot and was
      diaphoretic without shivering. With the exception of her temperature, her vital
      signs were normal postoperatively, and aside from hyperglycemia, complete blood
      count, electrolytes, thyroid-stimulating hormone, serum cortisol, troponin, and
      twelve-lead electrocardiogram were normal. Her temperature did not respond to
      warming efforts with a forced-air warming blanket, infusion of warmed intravenous
      crystalloid, and hourly bladder irrigation with warm saline through an indwelling
      urinary catheter. Normothermia returned after she received a small dose of
      sublingual lorazepam eight hours after surgery. The remainder of her
      postoperative stay was uneventful. CONCLUSION: Patients undergoing spinal
      anesthesia with intrathecal morphine may develop postoperative hypothermia that
      is resistant to warming measures. This complication may be treated successfully
      with lorazepam.

PMID- 22161245
TI  - Analysis of genetic variability at codon 42 within caprine prion protein gene in
      relation to production traits in Chinese domestic breeds.
AB  - In this study, genetic variability at codon 42 within prion protein (PRNP) gene
      and its associations with production traits were investigated in 2002 goats from
      four Chinese domestic breeds. The frequencies of allele "A" ranged from 0.353 to
      0.562 in analyzed goat breeds with Hardy-Weinberg equilibrium (P > 0.05) except
      Xinong Sannen (XNSN) dairy breed. The establishment of relationships between
      different genotypes and growth traits was performed in Inner Mongolia white
      Cashmere (IMWC) breed and revealed an association of the polymorphism with body
      weight at 7-year-old goats (P = 0.033). The individuals with genotype GG showed
      heavier body weight than those with genotype AA. Moreover, association analysis
      detected two significant associations between different genotypes and cashmere
      yield and fiber length in IMWC breed (P = 0.009, P = 0.048, respectively). In
      addition, three significant associations of different genotypes with density of
      milk (a.m. and p.m.), solids-not-fat of milk (P = 0.013, P = 0.009 and P =
      0.002), respectively, were found in XNSN breed. Genotype GG had better milk
      quality than others. These findings suggested that the polymorphism of codon 42
      within PRNP was a useful DNA marker for eliminating or selecting excellent
      individuals in relation to production traits in marker-assist selection breeding
      of goat.

PMID- 22161246
TI  - Post-transcriptional silencing of Notch2 mRNA in chronic lymphocytic [corrected]
      leukemic cells of B-CLL patients.
AB  - Environmental and genomic stresses induce different pathological conditions and
      one of them is blood cancer. This escalating load of disease with a constant
      threat to life requires an intensive comprehensive response. For our
      understanding about the cancer treatment capabilities, novel medicinal platforms
      should be strived to explore among the existing conventional and molecular
      approaches that have already been proven to be successful in fighting against
      genetic diseases. Several DNA therapeutics previously studied are currently in
      clinical settings. RNA interfering antisense oligonucleotide (AS-ODN) is the most
      experimentally advanced molecular therapeutic which has the potential to modify
      the gene activity resulting in the down regulation of particular protein. In this
      study, we focused on the inhibition of Notch2 function in B-cell chronic
      lymphocytic leukemia (B-CLL) by AS-ODN (phosphorothioate oligomers) targeted to
      the initiation codon region of the Notch2 mRNA. We investigated the in vitro
      ability of four such oligomers to reduce the expression of Notch2 gene in
      peripheral blood mononuclear cells from B-CLL patients. Our findings implicate
      that AS-ODNs specifically designed for the region of 314-333 neucleotides (AS1)
      of Notch2 inhibits its gene expression better than other AS-ODNs designed for
      other regions and respond in a dose dependent manner. The results of cell
      proliferation assay for the evaluation of AS1 in gene silencing, infer that the
      number of cells were reduced to 80% (P < 0.001). Our results implicate that using
      the AS-ODNs against specific Notch2 nucleotide sequence can be used as future
      therapeutic agent with the ability of Notch2 down regulation, which is the root
      problem in the pathogenicity of B-CLL.

PMID- 22161247
TI  - VEGF is essential for the growth and migration of human hepatocellular carcinoma
      cells.
AB  - Vascular endothelial growth factor (VEGF) plays a crucial role in tumor
      angiogenesis. VEGF induces new vessel formation and tumor growth by inducing
      mitogenesis and chemotaxis of normal endothelial cells and increasing vascular
      permeability. However, little is known about VEGF function in the proliferation,
      survival or migration of hepatocellular carcinoma cells (HCC). In the present
      study, we have found that VEGF receptors are expressed in HCC line BEL7402 and
      human HCC specimens. Importantly, VEGF receptor expression correlates with the
      development of the carcinoma. By using a comprehensive approaches including TUNEL
      assay, transwell and wound healing assays, migration and invasion assays,
      adhesion assay, western blot and quantitative RT-PCR, we have shown that
      knockdown of VEGF165 expression by shRNA inhibits the proliferation, migration,
      survival and adhesion ability of BEL7402. Knockdown of VEGF165 decreased the
      expression of NF-kappaB p65 and PKCalpha while increased the expression of p53
      signaling molecules, suggesting that VEGF functions in HCC proliferation and
      migration are mediated by P65, PKCalpha and/or p53.

PMID- 22161248
TI  - Association between the XRCC3 polymorphisms and breast cancer risk: meta-analysis
      based on case-control studies.
AB  - The previous published data on the association between X-ray repair cross
      complementing group 3 (XRCC3) T241M, A4541G, and A17893G polymorphisms and breast
      cancer risk remained controversial. Hence, we performed a meta-analysis to
      investigate the association between breast cancer and XRCC3 T241M (21,910 cases
      and 23,961 controls), A4541G (9,633 cases and 10,994 controls), and A17893G
      polymorphisms (10,761 cases and 12,235 controls) in different inheritance models.
      When all the eligible studies were pooled into the meta-analysis of XRCC3 T241M
      polymorphism, significantly increased risk of breast cancer was observed in
      recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04
      1.16) and in additive model (OR = 1.10, 95% CI = 1.03-1.16). No significant
      association was found between A4541G polymorphism and breast cancer risk. When
      all the eligible studies were pooled into the meta-analysis of XRCC3 A17893G
      polymorphism, no significant association was found in any genetic model.
      Additionally, when one study was deleted in the sensitive analysis, the results
      of XRCC3 A17893G were changed in the additive model (OR = 0.90, 95% CI = 0.82
      0.99) and dominant model (OR = 0.94, 95% CI = 0.89-0.99). In summary, this meta
      analysis indicates that T241M polymorphism show an increased breast cancer risk
      and A17893G polymorphism may be associated with decreased breast cancer risk. A
      study with the larger sample size is needed to further evaluated gene-environment
      interaction on XRCC3 T241M, A4541G, and A17893G polymorphisms and breast cancer
      risk.

PMID- 22161249
TI  - Determination of combined sibship indices "gray zone" using 15 STR loci for
      central Bosnian human population.
AB  - In our previous population studies of Bosnia and Herzegovina human population, we
      have used autosomal STR, Y-STR, and X-STR loci, as well as Y-chromosome NRY
      biallelic markers. All obtained results were included in Bosnian referent
      database. In order of future development of applied population molecular genetics
      researches of Bosnia and Herzegovina human population, we have examined the
      effectiveness of 15 STR loci system in determination of sibship by using 15 STR
      loci and calculating different cut-off points of combined sibship indices (CSI)
      and distribution of sharing alleles. From the perspective of its application, it
      is very difficult and complicated to establish strict CSI cut-off values for
      determination of the doubtless sibship. High statistically significant difference
      between the means of CSI values and in distribution of alleles sharing in
      siblings and non-siblings was noticed (P < 0.0001). After constructing the "gray
      zone", only one false positive result was found in three CSI cut-off levels with
      the highest percent of determined sibship/non-sibship at the CSI = 0.067,
      confirming its practical benefit. Concerning the distribution of sharing alleles,
      it is recommended as an informative estimator for its usage within Bosnia and
      Herzegovina human population.

PMID- 22161250
TI  - Prevention of type 2 diabetes: the strategic approach for implementation.
AB  - A growing need exists to deliver effective and affordable prevention programs and
      to take urgent action to address the major public health challenge that diabetes
      represents. Achieving prevention of type 2 diabetes requires moving through a
      series of steps from basic science discovery to widespread distribution of
      effective interventions. Understanding the cellular level influences on diabetes
      prevention will help target particular interventions to those who may be most
      responsive. Several randomized controlled trials conducted throughout the world
      have demonstrated that type 2 diabetes can be prevented or delayed. Subsequent
      real-world translation studies have provided important information necessary to
      reduce cost and increase access. Ultimately achieving a population impact in
      diabetes prevention requires widespread distribution of effective interventions,
      which is supported by policies that help achieve sustainability and reach. The
      use of a global stakeholder network can help to share experiences and build on
      partner knowledge gained.

PMID- 22161251
TI  - [Positive and negative feedback regulation in the production and secretion of
      insulin from INS-1 cells by testosterone. ].

PMID- 22161252
TI  - OPG-Fc treatment in growing pigs leads to rapid reductions in bone resorption
      markers, serum calcium, and bone formation markers.
AB  - Inhibition of the receptor activator of NF-kappaB ligand (RANKL) is a novel
      therapeutic option in the treatment of osteoporosis and related diseases. The aim
      of this study was to evaluate bone metabolism and structure in pigs after RANKL
      inhibition. 12 growing pigs were assigned to 2 groups with 6 animals each. The
      OPG group received recombinant human OPG-Fc (5 mg/kg IV) at day 0, the control
      group was given 0.9% NaCl solution. Serum levels of OPG-Fc, calcium (Ca),
      phosphorus (P), and bone turnover markers were evaluated every 5 days, and pigs
      were euthanized on day 20. Serum OPG-Fc concentration peaked at day 5 and
      coincided with significantly decreased Ca, P, and bone turnover markers. By day
      15, measureable OPG-Fc serum levels could only be detected in 2/6 animals. With
      OPG-Fc clearance starting at day 10, serum Ca and P concentrations were not
      different between the 2 groups. TRACP5b, P1CP, and BAP levels significantly
      decreased by 40-70% relative to vehicle controls in the OPG-Fc group between days
      5 and 10, indicating that pharmacologic concentration of OPG-Fc led to systemic
      concomitant inhibition of bone formation and resorption in young growing pigs.
      Dual X-ray absorptiometry data derived from the proximal femur did not differ
      between the 2 groups. MUCT analysis of selected bone sites demonstrated an OPG-Fc
      induced improvement of specific bone architectural indices and bone
      mineralization.

PMID- 22161253
TI  - Monitoring the active conformation of green fluorescent protein (GFP) and beta
      glucosidase adsorbed on soil particles.
AB  - In order to determine the effect of various soil components on the activity of
      proteins, we monitored the fluorescence and the enzymatic activity of,
      respectively, green fluorescent protein (GFP) and beta-glucosidase adsorbed on
      fine soil particles. We also monitored the activity of these proteins in the
      presence of components that are representative of soil colloids: a
      montmorillonite clay, goethite and organic matter extracted from soil. Upon
      adsorption on clay and goethite, GFP lost its fluorescence properties while beta
      glucosidase suffered only a partial loss of its catalytic activity. Extractable
      organic matter had an inactivating role on GFP while it did not cause
      inactivation of beta-glucosidase. When GFP and beta-glucosidase adsorbed on
      particles from natural soil samples, their behaviour was consistent with the
      behaviour observed for these proteins in the presence of the separate components,
      suggesting that the macroscopic activity of proteins adsorbed on soil particles
      corresponds to an average of the activities of proteins adsorbed on a mixture of
      surfaces. The monitoring of the proteins on soil particles with different organic
      matter contents has also shown that organic matter can have different effects
      (protecting or inactivating) on different proteins.

PMID- 22161255
TI  - Dynamics of defense-related components in two contrasting genotypes of tomato
      upon infection with Tomato Leaf Curl New Delhi Virus.
AB  - Tomato leaf curl virus (ToLCV) disease is a serious threat for tomato cultivation
      in the tropics and subtropics. Despite serious efforts no immune commercial
      varieties or F(1) hybrids are available till date. In this study, the interaction
      between Solanum lycopersicum and ToLCV was characterized on molecular and
      biochemical basis. RNA silencing mediated by short interfering RNA (siRNA) and
      reactive oxygen species (ROS) has been proposed as central components of plant
      adaptation to several stresses. A comparative RNA interference study between two
      contrasting tomato genotypes, LA1777 (tolerant) and 15SBSB (susceptible) infected
      with Tomato Leaf Curl New Delhi Virus (ToLCNDV) revealed relatively higher
      accumulation of siRNA in the leaves of tolerant genotype. In LA1777, ToLCNDV
      produced chlorotic as well as necrotic areas at the inoculation sites 5-10 days
      post-inoculation. Caspase-9- and caspase-3-like activities were significantly
      increased in response to ToLCNDV infection in LA1777 at inoculated region.
      Activities of antioxidant enzymes involved in the detoxification of ROS were
      examined in both systemic and localized area of infection, and their expression
      level was further validated through quantitative real-time PCR of the
      corresponding transcripts. Expression patterns of three genes encoding
      pathogenesis-related proteins showed higher accumulation in tolerant genotype.
      Tolerance against the ToLCNDV in LA1777 can be attributed to the higher siRNA
      accumulation, localized cell death, altered levels of antioxidant enzymes and
      activation of pathogenesis-related genes at different durations of virus
      infection. Based on these direct and indirect evidences, we have proposed a
      putative mechanism for ToLCNDV tolerance in the tolerant genotype.

PMID- 22161254
TI  - Routine invasive versus conservative management strategies in acute coronary
      syndrome: time for a "hybrid" approach.
AB  - The acute coronary syndrome is most often caused by plaque rupture and can result
      in a variety of clinical conditions. There are two general strategies (early
      invasive versus conservative) currently employed in the treatment of unstable
      angina or non-ST elevation myocardial infarction. Pooled data from recent
      clinical trials have demonstrated that high-risk patients benefit from a routine
      or early invasive approach while certain low-risk subgroups have similar outcomes
      with a conservative approach. Most patients in the USA are treated aggressively
      given advances in technology and the relative ease of interventional therapy. The
      routine invasive approach, however, remains controversial and has important
      limitations that are not well identified in trials. Furthermore, data from trials
      are difficult to interpret given their relevance to contemporary practice in
      today's cost conscious, health care environment. The decision to pursue an
      invasive or conservative approach should be based upon an individual patient's
      risk profile, and the level of medical therapy should be based on the underlying
      pathophysiology. The best strategy incorporates aggressive anti-atherosclerotic
      therapy with early risk stratification and invasive therapy when appropriate-the
      so-called hybrid approach. Identifying plaque rupture helps identify patients
      that would benefit from potent antiplatelet, antithrombotic, and anti
      inflammatory therapies, and further insight into the natural history of coronary
      artery disease coupled with continued advances in diagnostic and interventional
      approaches will hopefully help guide long-term primary and secondary management.

PMID- 22161257
TI  - Attendance at clinical visits predicts weight loss after gastric bypass surgery.
AB  - BACKGROUND: Clinicians working with patients who undergo bariatric surgery have
      found loss to follow-up challenging; however, the impact of this factor on
      postsurgical weight loss has not been adequately examined. The purpose of this
      study was to determine whether patients who returned for office visits after
      their gastric bypass (GBP) lost more weight than those who did not. METHODS: All
      patients treated with GBP by a single surgeon during 2003 were eligible. Measured
      weights were obtained from surgical and local physician records over 24 months
      after GBP. Attender status was defined by whether patients attended the 12-month
      post-GBP visit, and number of visits attended was recorded. When measured weights
      were not available at 1.5, 6, 12, or 24 months, the previous measured weight was
      carried forward. Weight loss over time was compared by attender group and by
      visit number using mixed models and >= 50% excess weight loss (EWL) by logistic
      regression. RESULTS: Weight loss was greater in attenders and men (both p <
      0.05). Increasing number of visits and BMI were associated with increased
      kilogram weight loss and %EWL (both p < 0.001). The odds of >= 50% EWL were 3.3
      fold greater at 12 months and 2.8-fold greater at 24 months with each unit
      increase in visit number (both p = 0.001). CONCLUSIONS: For optimal weight loss
      over 24 months after GBP, follow-up is important. Further studies are needed to
      develop strategies that will optimize follow-up and weight loss, and to evaluate
      whether a threshold number of clinic visits can be established.

PMID- 22161256
TI  - Screening of adult ADHD among patients presenting for bariatric surgery.
AB  - BACKGROUND: In the field of bariatric surgery, research on symptoms of adult
      attention deficit hyperactivity disorder (ADHD) and their interrelationships with
      other psychological risk factors such as depression and anxiety is scarce. The
      symptoms of adult ADHD seem to be common in the obese population, but they are
      rarely investigated before bariatric surgery. ADHD-related symptoms such as
      impulsivity have at the same time been identified as potential risk factors for
      less successful weight loss among bariatric surgery patients. The aims of the
      current study were to screen for symptoms of adult ADHD and to investigate their
      relationships with other psychological risk factors. METHODS: Candidates for
      bariatric surgery (N = 187) were anonymously screened for symptoms of anxiety,
      depression, and adult ADHD, in addition to disordered eating patterns, by means
      of questionnaires. The relations between these symptoms were investigated.
      RESULTS: In the current sample, 10% of patients screened positively for adult
      ADHD, and the symptoms of adult ADHD were significantly correlated with those of
      anxiety, depression, and disordered eating. CONCLUSIONS: The results show that
      adult ADHD is more common in this clinical group than in the general population
      (4%) and that adult ADHD is associated with disordered eating patterns,
      depression, and anxiety. Further prospective research, using multivariate
      analysis, is needed to investigate whether the symptoms of adult ADHD, and their
      interaction with anxiety, depression, or disordered eating, may possibly
      constitute a risk factor in terms of difficulties in adhering to the post-surgery
      regime and its potential unfavorable outcome.

PMID- 22161258
TI  - Characteristics of non-typhi Salmonella gastroenteritis associated with
      bacteremia in infants and young children.
AB  - PURPOSE: To characterize the clinical and laboratory manifestations of non-typhi
      Salmonella gastroenteritis associated with bacteremia in children less than 36
      months old. METHODS: The study group included 17 patients, aged 2-34 months, with
      non-typhi Salmonella gastroenteritis and bacteremia, hospitalized in a tertiary
      pediatric medical center during the period 1995-2010. Clinical data were
      collected by medical chart review. Culture-related data were taken from the
      microbiology laboratory files. The results were compared with an assigned, age
      matched, control group of 17 infants hospitalized with non-typhi Salmonella
      gastroenteritis without bacteremia. RESULTS: Eleven cases (65%) occurred during
      the summer season. All patients presented with diarrhea, usually mixed with blood
      or mucus (clinical dysentery 65%). All but one had a high-grade fever (average
      39.5 degrees C). Three patients (19%) experienced convulsions during the acute
      episode of gastroenteritis. None of the patients had been previously treated with
      antibiotics. The most prevalent Salmonella serotype identified in the stool and
      blood was group C. Toxic appearance and convulsions on admission were more common
      among children with non-typhi Salmonella bacteremia, as opposed to those with non
      typhi Salmonella gastroenteritis alone. No other epidemiological or laboratory
      differences were found. CONCLUSIONS: Non-typhi Salmonella gastroenteritis poses a
      risk of bacteremia not only in infants younger than 3 months of age, but also in
      children younger than 36 months of age.

PMID- 22161259
TI  - Changing epidemiology of methicillin-resistant Staphylococcus aureus in the
      Veterans Affairs Healthcare System, 2002-2009.
AB  - PURPOSE: The epidemiology of infections caused by methicillin-resistant
      Staphylococcus aureus (MRSA) is changing. Temporal trends and differences between
      healthcare settings must be described in order to better predict future risk
      factors associated with this dangerous bacterial infection. METHODS: A national
      MRSA-infected cohort was identified from 2002 to 2009 in the Veterans Affairs
      Healthcare System of the United States: hospital (HOS), long-term care (LTC), and
      outpatient (OPT). We analyzed within-setting time trends using generalized linear
      mixed models and between-setting differences with chi(2) and Wilcoxon rank-sum
      tests. RESULTS: The incidence of S. aureus, methicillin-susceptible S. aureus
      (MSSA), and MRSA infections increased significantly over time in all three
      settings based on modeled annual percentage changes (P < 0.001). MRSA incidence
      rates rose by 14, 10, and 37% per year in the HOS, LTC, and OPT settings,
      respectively. Among 56,345 MRSA-infected patients, the comorbidity burden was
      highest among LTC inpatients (n = 4,427) and lowest among outpatients (n =
      7,250), with an average absolute difference in specific comorbidities of +2 and 
      7%, respectively, compared to HOS inpatients (n = 44,668). Over time, there was a
      significant (P <= 0.02) decrease in previous inpatient admissions and surgeries
      (all settings); diabetes with complications and surgical site infections (HOS,
      OPT); and median length of stay and inpatient mortality (HOS, LTC).
      Alternatively, obesity, chronic renal disease, and depression were more common
      between 2002 and 2009 (P <= 0.02). CONCLUSIONS: Over the past 8 years, we
      observed significant changes in the epidemiology of MRSA infections, including
      decreases in traditional MRSA risk factors, improvements in clinical outcomes,
      and increases in other patient characteristics that may affect risk.

PMID- 22161260
TI  - Heterologous expression of a Nelumbo nucifera phytochelatin synthase gene
      enhances cadmium tolerance in Arabidopsis thaliana.
AB  - Phytochelatin synthase (PCS) is a key enzyme involved in the synthesis of
      phytochelatins, which are thought to play important roles in heavy metal
      detoxification. The sacred lotus (Nelumbo nucifera), one of the most popular
      ornamental species, has been shown to be a potential phytoremediator of heavy
      metal polluted water. However, the phytochelatin synthase gene in N. nucifera has
      not been identified yet. Here, we report the isolation and function
      characterization of a N. nucifera homologue of phytochelatin synthase. The
      sequence obtained shares a high degree of similarity with PCSs from other plant
      species and was named as Nelumbo nucifera phytochelatin synthase1 (NnPCS1). By
      using quantitative RT-PCR, we found that the expression of NnPCS1 in leaves of N.
      nucifera was dramatically increased in response to Cadmium (Cd) treatment. We
      further showed that, when exposed to Cd stress, Arabidopsis transgenic plants
      heterologous expressing NnPCS1 accumulated more Cd when compared with wild type.
      These results suggest that NnPCS1 involved in the response of N. nucifera to Cd
      stress and may represent a useful target gene for the phytoremediation of Cd
      polluted water.

PMID- 22161261
TI  - Metabolic engineering of Nocardia sp. CS682 for enhanced production of nargenicin
      A1.
AB  - A number of secondary metabolites having therapeutic importance have been
      reported from the genus Nocardia. One of the polyketide antibiotic compounds
      isolated from Nocardia is nargenicin A(1). Recently, nargenicin A(1) has been
      isolated from Nocardia sp. CS682, a new Nocardia strain isolated from soil in
      Jeonnam, South Korea. It possesses strong antibacterial activity against
      methicillin-resistant Staphylococcus aureus. In this study, we applied a
      metabolic engineering approach based on recombinant DNA technology in order to
      boost the production of nargenicin A(1) from Nocardia sp. CS682. Initially, we
      optimized the transformation of this new strain by electroporation method.
      Heterologous expression of S-adenosylmethionine synthetase (MetK1-sp) in Nocardia
      sp. CS682 enhanced the production of nargenicin A(1) by about 2.8 times due to
      transcriptional activation of biosynthetic genes as revealed by reverse
      transcription polymerase chain reaction analysis. Similarly, expression of acetyl
      CoA carboxylase genes improved nargenicin A(1) production by about 3.8 times in
      Nocardia sp. ACC18 compared to that in Nocardia sp. CS682 and Nocardia sp. NV18
      by increasing precursor pool. Thus, enhanced production of nargenicin A(1) from
      Nocardia sp. CS682 can be achieved by expression of transcriptional activator
      genes and precursor genes from Streptomyces strains.

PMID- 22161262
TI  - [Attitudes of winter sport participants toward ski helmet mandatory].
AB  - The aim of this study was to examine attitudes of winter sport participants
      toward a ski helmet mandatory. In total, 959 persons who had to estimate
      statements regarding ski helmet and helmet mandatory with the aid of a five level
      Likert scale were interviewed. About 85 % of interviewed persons totally agreed
      that a ski helmet reduces head injury risk although only 64 % are wearing a ski
      helmet. Significant more helmet wearers and females compared to non-wearers and
      males totally agreed that all winter sport participants should wear ski helmets
      on slopes as well as that all children on slopes should wear a ski helmet. Also,
      significant more helmet wearers and females compared to non-wearers and males
      totally agreed that a ski helmet mandatory for all people has to be recommended
      as well as that a ski helmet mandatory for children under 16 years has to be
      recommended. However, the acceptance for a helmet mandatory for all people as
      well as for children was significantly lower compared to recommendations for
      helmet use irrespective of helmet use or gender. Therefore, we conclude that
      preventive helmet campaigns possibly attain a higher acceptance leading to a
      higher helmet use compared to a helmet mandatory.

PMID- 22161263
TI  - [Skiing injuries in school sport and possibilioties to prevent them].
AB  - INTRODUCTION: Tyrol (Austria) is one of the regions which pioneered skiing.
      Skiing is considered as a national sport and is deeply rooted within the school
      system. Thus most pupils partake in skiing courses in this period. It is clear
      that such a large group of pupils also leads to a significant number of skiing
      injuries. Preventive issues may be derived from an analysis of the pattern and
      circumstances of skiing injuries. METHODS: During a period of ten years (2000 -
      2009) 1522 school sports injuries have been reported to the health insurance
      agency (Allgemeine Unfallversicherungsanstalt) from all secondary schools in
      Tyrol. RESULTS: The major disciplines were ski (48 %, n = 734) ice skateing (23
      %, n = 349) and snowboard injuries (21 %, n = 315), followed by tobogganing (6 %,
      n = 91), cross-country skiing (1 %, n = 17) and other wintersports (1 %, n = 16).
      Fractures (31 %) dominated in skiing, followed by contusions (23 %), and sprains
      (22 %). In the analysis of the distribution of injuries during alpine skiing
      accidents, lower extremity injuries (39 %) dominated followed by upper extremity
      injuries (34 %). Head and spine injuries (13 %) were rare. Analysing the
      circumstances of the injuries, most injuries during skiing occurred without
      person to person collision (82 %), 81 % either shortly before lunch-break or in
      the afternoon. CONCLUSION: Skiing injuries account for a significant proportion
      of all school sport-related injuries in Tyrol. Lower extremity injuries account
      for the vast majority of all injuries. Overestimation and overtiredness may be
      responsible for skiing sport injuries. Preventive measures such as a fitness
      training (e. g., skiing exercises) prior to skiing courses, appropriate breaks
      and proper protective gear (i. e., helmet and spine protector) may reduce the
      injury rate in skiing school sport.

PMID- 22161264
TI  - [Traumatology and sport injuries in professional and amateur show-jumping
      competitors].
AB  - The objective of this study was to investigate the frequency, extent, and
      effective preventive measures of sport injuries in professional and amateur-show
      jumping competitors. In a retrospective study design, 264 show-jumping riders
      (105 professionals, 159 amateurs) were interviewed by means of a standardised
      questionnaire. In total, 636 injuries were reported in detail. Injuries were
      categorised into severity grade I (36.0 %) (not requiring medical attention),
      grade II (34.6 %) (single medical treatment), grade III (20.9 %) (several
      outpatient medical treatments) and grade IV (8.5 %) (requiring hospitalisation).
      Specifically, 40.9 % of the reported injuries to professional riders and 23.9 %
      of those to amateurs were classified as severe (grade III or IV). The time
      related injury rate in professional athletes was 1.1 / 1000 h compared to 2.1 /
      1000 h in amateurs. The predominating types of sustained injuries were contusions
      (22 %), articular sprains (16 %) and abrasions (16 %). Fractures were reported in
      12 % of all injuries. There were 95 head injuries (15 %). The ratio between
      injured lower and upper extremities was 1.12 in professional athletes and 0.85 in
      amateur riders. Persistent pain at any site was reported by 33.7 %. Helmet use
      was reported in 89 % of professional and 94 % of amateur riders. In spite of a
      high level of expertise and longer experience, professional show-jumping riders
      seem to be at higher risk for sustaining severe injuries. Both performance
      oriented style of riding and readiness to assume risk are presumably factors
      leading to this increased rate of severe injuries. No significant differences
      were seen between the use of safety measures in amateur and professional
      athletes. While most of the riders indicated the regular use of protective head
      gear, craniocerebral injuries are still frequent. Taken together, besides a
      circumspect riding style, the wearing of helmets remains the most important
      safety measure.

PMID- 22161265
TI  - [Effects of compression textiles on performance enhancement and recovery].
AB  - INTRODUCTION: In competitive sports different types of compression garments
      (socks, shorts, tights and whole body suits) have become popular. The results of
      scientific studies regarding their effectiveness, however, are heterogeneous. The
      aim of this literature review is to (i) survey the scientific data regarding
      performance enhancing benefits and the support of recovery when applying
      compression fabrics and (ii) to describe the practical relevance for the
      application of compression textiles in the competitive sport context. METHOD: In
      order to detect relevant publications for the present review an internet search
      using the medical databases "Medline" and "PubMed" was performed. Altogether, 37
      studies were analysed. All publications were from the years 1987 to 2010.
      RESULTS: The literature review showed no general scientific indications regarding
      the benefit of compression garments in competitive sports. CONCLUSION: In
      particular, the different study designs and different clothing styles as well as
      different pressure gradients gave rise to contradictory data.

PMID- 22161266
TI  - [Cruciate ligament injuries under gender aspects].
AB  - An injury of cruciate ligament is one the most common knee injuries. This
      accident happens mostly without external impact and towards the end of training
      and competition sessions. Women, especially athletes playing team sports ball
      games such as soccer or disciplines such as tennis, are affected 2 to 8 times
      more often than men. Anatomic, biomechanical and endocrinological differences are
      currently discussed as potential risk factors. In terms of prevention,
      biomechanical impact is of greatest importance given its influenceability through
      various training opportunities. Training programs including endurance aspects,
      strengthening knee musculature, balance as well as plyometric trainings were most
      effective. Further studies should focus more on concomitants of course of
      injuries.

PMID- 22161267
TI  - [A false aneurysm as a rare complication of knee arthroscopy].
AB  - We present the rare case of a false aneurysm of the genus lat which occurred
      after knee arthroscopy. Apart from a pulse-synchronic swelling in close proximity
      to the former anterolateral portal there were no complaints and no pain. The
      diagnostic and therapeutic strategies - in this case performed with coiling of
      the involved vessel - are presented and discussed.

PMID- 22161268
TI  - [Fracture of the diaphyseal radius during Cyr wheel practice - an uncommon injury
      of wheel gymnastics].
AB  - The cyr wheel is a modified gymnastic wheel with only one ring that can lead to
      extreme forces on the gymnast. We report on a distal radius shaft fracture (AO 22
      A 2.1) and a fracture of the styloid process of the ulna that occurred after
      holding on to a slipping Cyr wheel and exposition to high pressure on the lower
      arm. The fracture was fixed by screws and a plate.

PMID- 22161270
TI  - Review article: closing the research gap at the interface of learning and
      clinical practice.
AB  - PURPOSE: The dialogue at the interface of education and clinical practice
      highlights areas of critical importance to the development of new approaches for
      educating anesthesiologists. The purpose of this article is to examine the
      literature on education and acquisition of competence in three areas relevant to
      the interface of learning and clinical practice, with the aim to suggest a
      research agenda that adds to the evidence on preparing physicians for independent
      practice. The three areas are: 1) transitions across the continuum of education;
      2) the effect of reductions in hours of clinical training on competence; and 3)
      efforts to incorporate the competencies and CanMEDS roles into teaching and
      evaluation. PRINCIPAL FINDINGS: Fifty-six articles relevant to one or more of the
      themes were identified in the review, including 21 studies of transitions (in,
      during, and after residency education), 19 studies on the effects of duty hour
      limits on residents' acquisition of competence, and 16 articles that assessed
      competency-based teaching and assessment in anesthesiology. Overall, the findings
      suggested a relative paucity of scientific evidence and a need for research and
      the development of new scientific theory. Studies generally treated one of the
      themes in isolation, while in actuality they interact to produce optimal as well
      as suboptimal learning situations, while medical education research often is
      limited by small samples, brief follow-up, and threats to validity. This suggests
      a "research gap" where editorials and commentaries have moved ahead of an
      evidence base for education. Promising areas for research include preparation for
      care deemed important by society, work to apply knowledge about the development
      of expertise in other disciplines to medicine, and ways to embed the competencies
      in teaching and evaluation more effectively. CONCLUSION: Closing the research gap
      in medical education will require clear direction for future work. The starting
      point, at an institution or nationally, is dialogue within the specialty to
      achieve consensus on some of the most pressing questions.

PMID- 22161269
TI  - Perforin plays an unexpected role in regulating T-cell contraction during
      prolonged Listeria monocytogenes infection.
AB  - After infection or vaccination, antigen-specific T cells proliferate then
      contract in numbers to a memory set point. T-cell contraction is observed after
      both acute and prolonged infections although it is unknown if contraction is
      regulated similarly in both scenarios. Here, we show that contraction of antigen
      specific CD8(+)  and CD4(+)  T cells is markedly reduced in TNF/perforin-double
      deficient (DKO) mice responding to attenuated Listeria monocytogenes infection.
      Reduced contraction in DKO mice was associated with delayed clearance of
      infection and sustained T-cell proliferation during the normal contraction
      interval. Mechanistically, sustained T-cell proliferation mapped to prolonged
      infection in the absence of TNF; however, reduced contraction required the
      additional absence of perforin since T cells in mice lacking either TNF or
      perforin (singly deficient) underwent normal contraction. Thus, while T-cell
      contraction after acute infection is independent of peforin, a perforin-dependent
      pathway plays a previously unappreciated role to mediate contraction of antigen
      specific CD8(+)  and CD4(+)  T cells during prolonged L. monocytogenes infection.

PMID- 22161271
TI  - Review article: leading the future: guiding two predominant paradigm shifts in
      medical education through scholarship.
AB  - PURPOSE: The purpose of this article is to consolidate some of the key concepts
      about scholarship in education related to the specialty of anesthesiology. We
      frame the discussion on two paradigm shifts in medical education, i.e.,
      competency-based education and lifelong learning, and the scholarly approaches to
      lead these paradigm shifts in anesthesiology. PRINCIPAL FINDINGS: Conventional
      medical education is being challenged by a shift from time-based education to
      competency-based education. This potential shift will also create a continuous
      need to foster a culture of lifelong learning in contrast with the traditional
      compartmentalized model of undergraduate, postgraduate, and continuing medical
      education. The specialty of anesthesia has the capacity to lead these changes by
      enhancing scholarship in education locally and nationally. The promotion of
      scholarship in education necessitates the creation of infrastructure and
      accountability frameworks to show return on investment. High-quality scholarship
      in medical education requires a solid rationale and, ultimately, a demonstrable
      benefit to patient care. CONCLUSION: Accountability of lifelong learning to
      established competency frameworks seems inevitable. Anesthesiology is one of only
      a few specialties that can truly protect faculty from clinical responsibilities
      in favour of scholarship pursuits. With appropriate support for scholarship in
      education, anesthesiologists have an opportunity to lead these paradigm shifts.

PMID- 22161273
TI  - Acute liver failure: what is it?

PMID- 22161272
TI  - Considerations for Endpoint Selection When Designing HIV Clinical Trials.
AB  - Selecting the primary endpoint is one of the most important decisions in
      designing clinical trials. Many HIV trials are powered for surrogate markers,
      often virologic suppression. Among 49 recently published Phase 3 or higher
      randomized HIV trials only 14% were powered for clinical outcomes such as the
      progression to AIDS, death, or serious non-AIDS diseases. We provide two examples
      where interventions modified the targeted surrogate markers but failed to provide
      clinical benefit. We review the use of surrogate and clinical endpoints, discuss
      the composition of clinical endpoints, and the need for endpoint verification. In
      HIV-infected individuals with CD4 cell counts above 200 cells/mm(3) serious non
      AIDS conditions such as cardiovascular, renal, hepatic diseases and cancer
      contribute substantially to morbidity and mortality. In this population clinical
      endpoint trials should be powered for non-AIDS morbidity along with AIDS.

PMID- 22161274
TI  - Cadmium a metalloestrogen: are we convinced?
AB  - Metalloestrogens are inorganic metal ions that bind to and activate oestrogen
      receptors. They are implicated in the aetiology of oestrogen-dependent diseases
      such as cancers of the breast and endometrium as well as endometriosis. Cadmium
      is one of the most studied metalloestrogens. In this review, scientific evidence
      for the oestrogenic effects of cadmium is critically evaluated to determine if
      there is sufficient evidence to support cadmium as an aetiological factor of
      oestrogen-dependent disease in humans. Results of the review indicated that,
      although the in vitro and in vivo evidence of the oestrogenic properties of
      cadmium was persuasive, evidence from population-based human studies remains
      conflicting. Considerable knowledge gaps exist on the potential oestrogenic
      effect of cadmium in humans. Research that focuses on bridging these knowledge
      gaps would be useful in preventing and managing oestrogen-dependent disease in
      humans.

PMID- 22161275
TI  - Bayesian adjusted R2 for the meta-analytic evaluation of surrogate time-to-event
      endpoints in clinical trials.
AB  - A two-stage model for evaluating both trial-level and patient-level surrogacy of
      correlated time-to-event endpoints has been introduced, using patient-level data
      when multiple clinical trials are available. However, the associated maximum
      likelihood approach often suffers from numerical problems when different baseline
      hazards among trials and imperfect estimation of treatment effects are assumed.
      To address this issue, we propose performing the second-stage, trial-level
      evaluation of potential surrogates within a Bayesian framework, where we may
      naturally borrow information across trials while maintaining these realistic
      assumptions. Posterior distributions on surrogacy measures of interest may then
      be used to compare measures or make decisions regarding the candidacy of a
      specific endpoint. We perform a simulation study to investigate differences in
      estimation performance between traditional maximum likelihood and new Bayesian
      representations of common meta-analytic surrogacy measures, while assessing
      sensitivity to data characteristics such as number of trials, trial size, and
      amount of censoring. Furthermore, we present both frequentist and Bayesian trial
      level surrogacy evaluations of time to recurrence for overall survival in two
      meta-analyses of adjuvant therapy trials in colon cancer. With these results, we
      recommend Bayesian evaluation as an attractive and numerically stable alternative
      in the multitrial assessment of potential surrogate endpoints.

PMID- 22161276
TI  - Preoperative CT evaluation of intraductal spread of breast cancer and surgical
      treatment.
AB  - It is always a challenge to accurately determine the appropriate extent of
      resection in breast-conserving surgery (BCS), in order to reduce the need for re
      excision, prevent local recurrence, and optimize cosmetic results. Detecting
      intraductal spread alone with high sensitivity may not be enough to realize safe
      BCS. Computed tomography carried out with the patient in the supine position
      accompanied by adequate marking is effective for preoperative determination of
      the optimum extent of BCS.

PMID- 22161277
TI  - Diffusion-weighted imaging (b value = 1500 s/mm(2)) is useful to decrease false
      positive breast cancer cases due to fibrocystic changes.
AB  - BACKGROUND: We aimed to evaluate the application of apparent diffusion
      coefficient (ADC) values calculated from diffusion-weighted imaging (DWI) (b
      value = 1500 s/mm(2)) in the breast imaging reporting and data system (BI-RADS).
      METHODS: For 104 cases of breast lesions with definitive histology diagnosis (45
      benign cases, 59 malignant cases) in which breast magnetic resonance imaging was
      performed, ADC values were compared between benign and malignant cases, between
      ductal carcinoma in situ (DCIS) and fibrocystic changes, and between DCIS and
      ductal hyperplasia (one type of fibrocystic change). Diagnostic accuracy was
      compared for a total of 101 images and for 34 images including only nine DCIS and
      25 fibrocystic changes between BI-RADS alone (with categories 4a, 4b, and 5
      defined as malignancies) and BI-RADS plus ADC. RESULTS: There were significant
      differences in mean ADC values between malignant and benign cases (p < 0.0001)
      and between DCIS and fibrocystic changes (p < 0.002), but not between DCIS and
      ductal hyperplasia. Positive predictive values were significantly greater for BI
      RADS plus ADC than for BI-RADS alone in all cases (70.5% for BI-RADS alone, 81.3%
      for BI-RADS plus ADC) and in cases of DCIS versus fibrocystic changes (40.9% for
      BI-RADS alone, 64.3% for BI-RADS plus ADC), resulting in a significant
      improvement in diagnostic accuracy with the addition of ADC. CONCLUSION: Adding
      ADC values calculated from DWI (b value = 1500 s/mm(2)) to BI-RADS is a useful
      way to improve differential diagnostic accuracy for malignant tumors and benign
      lesions, especially for DCIS versus fibrocystic changes, except in cases of
      ductal hyperplasia.

PMID- 22161278
TI  - Costal hydatidosis: management and outcome of five cases.
AB  - The objective of the study was to report our experience in the management of
      hydatid cyst of the rib. Between December 2001 and December 2009, five patients
      underwent surgery for costal echinococcosis, among 234 cases of thoracic hydatid
      cyst managed in our department. They were three males and two females, aged 19-42
      years (mean = 32.2 years). Imaging investigations consisted of chest X-ray and
      computed tomography. All the patients underwent thoracotomy along the arch of the
      infected rib. Albendazole was administered postoperatively in all cases. The
      echinococcosis of the rib was primary in 3 cases, and secondary to thoracic
      localization in 2 cases. It was located on the right side in four patients, on
      the left one in one patient. The posterior arch was the site of infection in 3
      cases, and the anterior arch in 2 cases. The cyst was intact in 4 cases, and the
      invasion of adjacent structures was found in one case. There were no concomitant
      hydatid lesions. The resection of the infected rib was total in 2 cases and
      partial in 3 cases. There was no postoperative mortality or complications. The
      follow-up ranged from 28 months to 8 years did not show any recurrence.
      Echinococcosis of the rib is very rare. To avoid complications and to allow the
      eradication of the disease, the combination of surgery and antihelmentic drugs
      remains the best therapeutic choice.

PMID- 22161280
TI  - C.U.R.R.F. (Codon Usage regarding Restriction Finder): a free Java((r))-based
      tool to detect potential restriction sites in both coding and non-coding DNA
      sequences.
AB  - The synthesis of complete genes is becoming a more and more popular approach in
      heterologous gene expression. Reasons for this are the decreasing prices and the
      numerous advantages in comparison to classic molecular cloning methods. Two of
      these advantages are the possibility to adapt the codon usage to the host
      organism and the option to introduce restriction enzyme target sites of choice.
      C.U.R.R.F. (Codon Usage regarding Restriction Finder) is a free Java((r))-based
      software program which is able to detect possible restriction sites in both
      coding and non-coding DNA sequences by introducing multiple silent or non-silent
      mutations, respectively. The deviation of an alternative sequence containing a
      desired restriction motive from the sequence with the optimal codon usage is
      considered during the search of potential restriction sites in coding DNA and
      mRNA sequences as well as protein sequences. C.U.R.R.F is available at
      http://www.zvm.tu
      dresden.de/die_tu_dresden/fakultaeten/fakultaet_mathematik_und_naturwissenschafte
      /fachrichtung_biologie/mikrobiologie/allgemeine_mikrobiologie/currf.

PMID- 22161281
TI  - Nanostructured material surfaces--preparation, effect on cellular behavior, and
      potential biomedical applications: a review.
AB  - Nanostructures play important roles in vivo, where nanoscaled features of
      extracellular matrix (ECM) components influence cell behavior and resultant
      tissue formation. This review summarizes some of the recent developments in
      fostering new concepts and approaches to nanofabrication, such as top-down and
      bottom-up and combinations of the two. As in vitro investigations demonstrate
      that man-made nanotopography can be used to control cell reactions to a material
      surface, its potential application in implant design and tissue engineering
      becomes increasingly evident. Therefore, we present recent progress in directing
      cell fate in the field of cell mechanics, which has grown rapidly over the last
      few years, and in various tissue-engineering applications. The main focus is on
      the initial responses of cells to nanostructured surfaces and subsequent
      influences on cellular functions. Specific examples are also given to illustrate
      the potential nanostructures may have for biomedical applications and
      regenerative medicine.

PMID- 22161279
TI  - IKKbeta-induced inflammation impacts the kinetics but not the magnitude of the
      immune response to a viral vector.
AB  - Microbial adjuvants in vaccines activate key transcription factors, including NF
      kappaB and interferon response factors (IRFs). However, the individual role of
      these transcription factor pathways in promoting adaptive immunity by adjuvants
      is not clear. It is widely believed that induction of a strong inflammatory
      response potentiates an adaptive immune response. In this study, we sought to
      determine whether activation of the pro-inflammatory inhibitor of kappaB kinase
      beta (IKKbeta) canonical NF-kappaB pathway promoted vaccine-induced immune
      responses. An adenovirus expressing constitutively activated IKKbeta (AdIKK)
      induced robust DC maturation and high expression of key cytokines compared with a
      control virus. In vivo, AdIKK triggered rapid inflammation after pulmonary
      infection, increased leukocyte entry into draining LNs, and enhanced early
      antibody and T-cell responses. Notably, AdIKK did not influence the overall
      magnitude of the adaptive immune response. These results indicate that induction
      of inflammation by IKKbeta/NFkappaB in this setting impacts the kinetics but not
      the magnitude of adaptive immune responses. These findings therefore help define
      the individual role of a key pathway induced by vaccine adjuvants in promoting
      adaptive immunity.

PMID- 22161282
TI  - A review of developments in electrospinning technology: new opportunities for the
      design of artificial tissue structures.
AB  - PURPOSE: As a technology for the production of micro- and nanostructured scaffold
      materials, electrospinning has gained widespread acceptance in the medical
      research community over the last decade. The process generates a non-woven fiber
      mat consisting of one continuous filament with diameters ranging from the micron
      to the nanometer range. Because of its similarity to the filamentous
      microenvironment in native tissues, it is most often used as scaffold material in
      tissue engineering applications. This similarity promotes a more positive cell
      response to the generated fibers than to bulk material alone. However, because
      current electrospinning equipment does not yet fully utilize the potential of the
      process technology, the reproducibility of the scaffold structure is often
      limited. It is thus the goal of this review to describe the current state of
      electrospinning process technology with respect to the design of artificial
      tissue structures. METHOD: This review is based on a comprehensive examination
      conducted in 2007 and 2008 of patents filed with the European Patent Organization
      and other scientific publications. RESULTS: It describes selected technical
      developments in electrospinning related to the production of non-woven fiber
      scaffolds and their implications in the design of artificial tissue structures.
      Specifically, it describes techniques for the production of aligned fiber
      structures, multilayered, multiscaled and multifiber scaffolds, fiber
      modification and functionalization, and useful advances in process control. It
      also presents technical sketches showing in detail how to implement the
      techniques presented into electrospinning equipment setups. Finally, it discusses
      remaining limitations that pertain to the design of scaffold materials.

PMID- 22161283
TI  - Effects of osteogenic differentiation inducers on in vitro expanded adult
      mesenchymal stromal cells.
AB  - PURPOSE: For bone regeneration therapy using stem cells, well-defined ex vivo
      protocols to expand mesenchymal stromal cells (MSC), as well as assays to show
      their potential differentiation into the osteogenic lineage, are needed. Aim of
      this study was to analyze the role of the biochemical osteogenic inducers, i.e.
      ascorbic acid, dexamethasone, and beta-glycerophosphate, employed in the current
      protocols for osteogenic differentiation of MSC in vitro, to address the
      requirements for reliable differentiation systems. METHODS: MSC were isolated
      from the bone marrow of donors (46-73 years of age) undergoing total hip
      replacement, and expanded in vitro. At confluence, MSC were cultured under four
      different conditions: alpha-MEM plus serum (basal medium or C1), basal medium
      plus ascorbate (C2), basal medium plus ascorbate and dexamethasone (C3), or basal
      medium plus ascorbate, dexamethasone and beta-glycerophosphate (C4). Morphology,
      proliferation, mineralization, alkaline phosphatase, collagen and expression of
      bone-related genes of MSC under the different media were analyzed at fixed time
      points. RESULTS: MSC proliferation and the number of colony forming units were
      increased by ascorbic acid, whereas dexamethasone enhanced the proportion of ALP
      positive CFU and was critical for mineral deposition. Runx-2 and type I collagen
      gene expression decreased along with additive-induced MSC differentiation, i.e.
      from C1 to C4, while ALP and osteocalcin were differently regulated. CONCLUSION:
      Our findings support the role of different inducers on the sequential stages of
      MSC expansion and osteogenic differentiation in vitro, suggesting the addition of
      DEX following proliferation to ensure mineralization, as an index of in vivo
      osteogenic potency of human mesenchymal cells.

PMID- 22161284
TI  - Differentiation of embryonic stem cells into neural cells on 3D poly (D, L-lactic
      acid) scaffolds versus 2D cultures.
AB  - In this study, a highly porous poly (D, L-lactic acid) (PDLLA) scaffold was
      designed and fabricated using dioxane and thermal-induced phase separation (TIPS)
      methods (liquid-liquid and solid-liquid). Additionally, we characterized the
      ability of mouse embryonic stem cells (ESCs) to differentiate into neural cells
      in PDLLA scaffold with uniform porosity, interconnectivity, and high porosity,
      and then compared them with cells seeded under conventional two-dimensional (2D)
      culture conditions. Histochemistry staining showed the migration of
      differentiated cells through the scaffold. Immunofluorescence analysis of the
      differentiated cells by counting positive cells revealed that the PDLLA scaffold
      resulted in a significantly greater number of neural markers, microtubule
      associated protein-2, beta-tubulin III, neurofilament protein, and glial
      fibrillary acidic protein (the astrocyte marker) when compared to those in 2D
      culture condition. Moreover, the expression of Nestin, Mash1, Pax6, and HB9
      increased significantly in 3D scaffolds when compared with 2D cultures as
      detected by semi-quantitative RT-PCR. Scanning electron microscopy of
      differentiated neurons on scaffolds also demonstrated favorable results for
      neurite outgrowth. The results of this study demonstrated a promising effect of
      3D scaffold culture for neural cell differentiation from ESCs in prospective
      tissue engineering applications.

PMID- 22161285
TI  - Effects of arteriovenous fistula on clinical, laboratory and echocardiographic
      findings in renal allograft recipients.
AB  - PURPOSE: Left ventricular hypertrophy (LVH) is frequently observed in patients
      with end-stage renal disease and renal allograft recipients, and is an
      independent and strong predictor of morbidity and mortality. Presence of a patent
      arteriovenous fistula (AVF) after renal transplantation may contribute to the
      persistent LVH. We investigated the clinical, laboratory, and echocardiographic
      findings in patients with renal transplants with or without AVF. METHODS: A total
      of 130 renal transplant recipients were included in this study: 60 hemodialysis
      patients whose fistulas were still functional, 49 hemodialysis patients whose
      fistulas were spontaneous stopped or closed, and 21 peritoneal dialysis patients
      who had never had fistulas created. Laboratory parameters were measured and
      echocardiographic measurements were performed. RESULTS: There were no significant
      differences regarding smoking status, blood pressures, or NT-proBNP, hs-CRP,
      iPTH, and TSH levels between the study groups. Left atrial, right atrial
      diameters, left ventricle end-diastolic diameter, left ventricle end-systolic
      diameter, interventricular septum thickness (IVST), left ventricle mass index
      (LVMI), pulmonary artery pressure (PAP), and ejection fraction were similar in
      the three groups. In correlation analysis, PAP was significantly correlated with
      serum uric acid and NT-proBNP levels. Also, there were positive and moderate
      correlations between the serum uric acid and the IVST. CONCLUSION: Patent AVFs
      have not affected cardiovascular abnormalities such as LVH and LV mass index in
      patients with renal transplant. Hyperuricemia may be associated with increased
      PAP and high LVMI.

PMID- 22161286
TI  - HBV-related liver disease in renal insufficiency: successful antiviral therapy
      with entecavir.
AB  - Hepatitis B virus (HBV) infection persists among patients with renal
      insufficiency in the industrialized world. A variety of therapeutic options are
      now available for the treatment of chronic hepatitis B infection, including
      potent new nucleos(t)ide analogs, along with standard and pegylated interferon.
      We report on a patient with aggressive hepatitis B and renal insufficiency who
      was successfully treated with nucleoside analogs (mostly entecavir monotherapy)
      for two years. He received intense immunosuppression for severe myopathy of lower
      limbs, probably related to vasculitis. HBV DNA (at the beginning, > 1 x 10(8)
      IU/mL) was no longer detectable in serum after a few months of antiviral therapy,
      while HBeAg and HBsAg seroconversion occurred with ALT normalization. Clinical
      signs of vasculitis disappeared. Five months after discontinuation of entecavir
      therapy, he remained HBsAg negative with detectable anti-HBs antibody in serum.
      We conclude that nucleos(t)ide analogs can offer excellent response in selected
      patients with renal insufficiency and hepatitis B-related liver disease.
      Prospective, controlled clinical trials are needed to confirm these encouraging
      results.

PMID- 22161287
TI  - Magnetorelaxometry assisting biomedical applications of magnetic nanoparticles.
AB  - Due to their biocompatibility and small size, iron oxide magnetic nanoparticles
      (MNP) can be guided to virtually every biological environment. MNP are
      susceptible to external magnetic fields and can thus be used for transport of
      drugs and genes, for heat generation in magnetic hyperthermia or for contrast
      enhancement in magnetic resonance imaging of biological tissue. At the same time,
      their magnetic properties allow one to develop sensitive and specific measurement
      methods to non-invasively detect MNP, to quantify MNP distribution in tissue and
      to determine their binding state. In this article, we review the application of
      magnetorelaxometry (MRX) for MNP detection. The underlying physical properties of
      MNP responsible for the generation of the MRX signal with its characteristic
      parameters of relaxation amplitude and relaxation time are described. Existing
      single and multi-channel MRX devices are reviewed. Finally, we thoroughly
      describe some applications of MRX to cellular MNP quantification, MNP organ
      distribution and MNP-based binding assays. Providing specific MNP signals, a
      detection limit down to a few nanogram MNP, in-vivo capability in conscious
      animals and measurement times of a few seconds, MRX is a valuable tool to improve
      the application of MNP for diagnostic and therapeutic purposes.

PMID- 22161288
TI  - Preparation and biological effect of nucleotide-capped CdSe/ZnS quantum dots on
      Tetrahymena thermophila.
AB  - In this paper, we described the preparation and characterization of different
      types of modified CdSe/ZnS quantum dots (QDs) and explored the biological effects
      of QDs with different surface modifications on the whole growth of unicellular
      protozoan Tetrahymena thermophila BF(5) using a thermal activity monitor air
      isothermal microcalorimeter. Our results demonstrated that adenosine 5'
      monophosphate (AMP) showed stronger interaction with QDs than other types of
      nucleotide. AMP-QDs could stimulate the growth of T. thermophila while
      mercaptoacetic acid-capped CdSe/ZnS quantum dots inhibited it. In addition, the
      population density determination and fluorescence imaging of T. thermophila BF(5)
      also confirmed the results obtained from microcalorimetry. It is believed that
      this approach will provide a more convenient methodology for the kinetics and
      thermodynamics of microorganism when coexisting with QDs in real time, and all of
      which are very significant to understanding the effect of QDs to organism.

PMID- 22161289
TI  - The influence of selenium on root growth and oxidative stress induced by lead in
      Vicia faba L. minor plants.
AB  - The effect of selenium (Se) on Vicia faba L. minor roots subjected to lead (Pb)
      stress was studied by investigating root growth, root viability, and antioxidant
      enzyme activity. The experiments were carried out on plants grown for 2 weeks on
      Hoagland medium supplied with 50 MUM Pb in the form of lead nitrate Pb(NO(3))(2)
      and/or Se concentrations of 1.5 and 6 MUM in the form of sodium selenite
      Na(2)SeO(3). It was shown that Pb reduced the root growth and caused serious
      damage in the roots, which was accompanied by metal accumulation in these
      tissues. The exposition of roots to Pb led to significant changes in the
      biochemical parameters: the MDA and T-SH content and glutathione peroxidase (GSH
      Px) activity increased but the guaiacol peroxidase (GPOX) activity decreased.
      Moreover, Pb intensified O(2)(.-) production in the roots. Selenium at a lower
      concentration alleviated Pb toxicity which was accompanied by a decreased O(2)(.
      ) production in the apical parts of roots and increased the T-SH content and GPOX
      activity. However, higher Se concentration intensified MDA and T-SH accumulation
      and GPOX and GSH-Px activity in Pb-treated plant roots. At low concentration, Se
      improved cell viability whereas at high concentration it was pro-oxidant and
      enhanced the lipid peroxidation and cell membrane injury.

PMID- 22161290
TI  - Efficacious outcome employing fecal bacteriotherapy in severe Crohn's colitis
      complicated by refractory Clostridium difficile infection.

PMID- 22161291
TI  - Severe hypoxemia in a patient with massive leukocytosis.

PMID- 22161292
TI  - Stars in the sky: neurocysticercosis.

PMID- 22161293
TI  - QTc pseudoprolongation and hypokalemia-induced T-U fusion: the authors reply.

PMID- 22161294
TI  - Beyond 9/11: health consequences of the terror attacks outside the USA.

PMID- 22161295
TI  - Run performance of middle-aged and young adult runners in the heat.
AB  - The aging process may impair exercise tolerance in the heat. It is not clear
      whether this impairment is partly due to a reduction in aerobic capacity. To
      compare the exercise performance and thermoregulatory responses of middle-aged
      and young adults with similar aerobic capacities and training statuses, 7 middle
      aged (54+/-2 years; 58+/-4 ml.kg - 1.min - 1) and 7 young (28+/-1 years; 61+/-5
      ml.kg - 1.min - 1) male competitive endurance runners underwent 2 10-km self
      paced and 2 fixed-workload (90% of race speed) runs until fatigue on a treadmill
      in hot (40 degrees C) and moderate (20 degrees C) environments on separate days.
      The runners' total time, average speed, rectal temperature, heat storage rate,
      physiological strain index, sweat rate, sweat sensitivity, number of heat
      activated sweat glands and sweat rate per sweat gland were measured or
      calculated. Body fat, body surface area, body surface area per body mass,
      training volume and VO2max were similar between the 2 groups. No differences were
      observed in total time (59+/-3; 49+/-3; 27+/-2; 54+/-5 min in the middle-aged and
      60+/-2; 49+/-3; 27+/-2; 51+/-4 min in the young group), average speed, rectal
      temperature, heat storage rate, physiological strain index, sweat rate (17+/-7;
      15+/-3; 23+/-7; 13+/-2 g.m - 2.min - 1 in the middle-aged and 20+/-5; 14+/-4;
      22+/-5; 15+/-4 g.m - 2.min - 1 in the young group) or sweat sensitivity between
      age groups (p>0.05) in any trial. The number of heat-activated sweat glands (88+/
      14; 80+/-18; 90+/-16; 66+/-14 cm - 2 in the middle-aged and 43+/-10; 32+/-10;
      37+/-11; 31+/-11 cm - 2 in the young group) was higher, and the sweat rate per
      sweat gland was smaller, in the middle-aged than the young group (p<0.05) in all
      of the trials. We conclude that running performance and body thermoregulation are
      similar between young and middle-aged runners with similar aerobic capacities and
      training statuses under hot and moderate conditions in self-paced and fixed
      intensity runs. The decrease observed in the sweat rate per sweat gland in middle
      aged men was compensated for by a higher number of heat-activated sweat glands.

PMID- 22161296
TI  - Philips monitors: catch the wave!

PMID- 22161297
TI  - Equilibrium, kinetic and thermodynamic studies on the biosorption of reactive
      acid dye on Enteromorpha flexuosa and Gracilaria corticata.
AB  - PURPOSE: Biosorption is an emerging, eco-friendly and economical method for
      treating the wastewater effluents. Compared to many other biological materials,
      algae biomass proved to be the better biosorbent due to the presence of cell wall
      polymers in them. METHODS: Algal biomasses namely Enteromorpha flexuosa and
      Gracilaria corticata were dried, crushed and used as biosorbents. Ponceau S, a
      diazo dye was used as a model adsorbate for the biosorption studies. The
      biosorbents were characterized by Scanning Electron Microscopy, FT-IR and zero
      point charge. Batch studies were performed by varying pH, biosorbent dosage and
      initial dye concentrations. Adsorption isotherms, kinetic and thermodynamic
      analyses were carried out. The effect of electrolytes was also studied. Batch
      desorption studies were also carried out using various reagents. RESULTS:
      Isotherm data were tested with Langmuir and Freundlich isotherm models and the
      results suggested that the Freundlich isotherm fitted the data well. Kinetic
      studies were performed with varying initial dye concentrations and the data were
      incorporated with pseudo first-order and pseudo second-order kinetic equations
      and was found that the studied biosorption processes followed pseudo second-order
      kinetic equation. Thermodynamic parameters were evaluated at three different
      temperatures 293 K, 300 K and 313 K. About 95% of the dye could be desorbed from
      both the biosorbents. CONCLUSION: Both the algal biomasses had heterogeneous
      surfaces and followed pseudo second-order chemical kinetics. Thermodynamic
      parameters proved that the biosorption by both the biomasses were spontaneous,
      feasible and endothermic processes. Desorption studies proved the worth of the
      algal biomasses as biosorbents in industrial level.

PMID- 22161298
TI  - Bacterial assisted phytoremediation for enhanced degradation of highly sulfonated
      diazo reactive dye.
AB  - PURPOSE: Phytoremediation is the exploitation of plants and their rhizospheric
      microorganisms for pollutants treatment like textile dyes, which are toxic,
      carcinogenic and mutagenic from the effluent. The purpose of this work was to
      explore a naturally found plant and bacterial synergism to achieve an enhanced
      degradation of Remazol Black B dye (RBB). METHODS: In vitro cultures of Zinnia
      angustifolia were obtained by seed culture method. Enzymatic analysis of the
      plant roots and Exiguobacterium aestuarii strain ZaK cells was performed before
      and after decolorization of RBB. Metabolites of RBB formed after its degradation
      were analyzed using UV-Vis spectroscopy, high-performance liquid chromatography
      (HPLC), Fourier transform infrared (FTIR) and gas chromatography-mass
      spectrometry (GC-MS). Phytotoxicity studies were performed. RESULTS: The
      consortium ZE was found to be more efficient than individual plant and bacteria.
      Z. angustifolia roots showed significant induction in the activities of lignin
      peroxidase, laccase, DCIP reductase and tyrosinase during dye decolorization. E.
      aestuarii showed significant induction in the activities of veratryl alcohol
      oxidase, azo reductase and DCIP reductase. Analysis of metabolites revealed
      differential metabolism of RBB by plant, bacteria and consortium ZE. E. aestuarii
      and Z. angustifolia led to the formation of 3,6-diamino-4-hydroxynaphthalene-2
      sulfonic acid, (ethylsulfonyl)benzene, and 3,4,6-trihydroxynaphthalene-2-sulfonic
      acid and propane-1-sulfonic acid, respectively, whereas consortium ZE produced 4
      hydroxynaphthalene-2-sulfonic acid, naphthalene-2-sulfonic acid and 4
      (methylsulfonyl)phenol. The phytotoxicity study revealed the nontoxic nature of
      the metabolites formed after dye degradation. CONCLUSION: Consortium ZE was found
      to be more efficient and faster in the degradation of RBB when compared to
      degradation by Z. angustifoila and E. aestuarii individually.

PMID- 22161299
TI  - Comparison of two wild rodent species as sentinels of environmental contamination
      by mine tailings.
AB  - BACKGROUND: Contamination with heavy metals is among the most hazardous
      environmental concerns caused by mining activity. A valuable tool for monitoring
      these effects is the use of sentinel organisms. Particularly, small mammals
      living inside mine tailings are an excellent study system because their analysis
      represents a realistic approach of mixtures and concentrations of metal exposure.
      PURPOSE: We analyzed metal tissue concentrations and DNA damage levels for
      comparison between genders of a sentinel (Peromyscus melanophrys) and a
      nonsentinel (Baiomys musculus) species. Also, the relationship between DNA damage
      and the distance from the contamination source was evaluated. METHODS: This study
      was conducted in an abandoned mine tailing at Morelos, Mexico. Thirty-six
      individuals from both species at the exposed and reference sites were sampled.
      Metal concentrations in bone and liver of both species were analyzed by atomic
      absorption spectrophotometry, and DNA damage levels were assayed using the
      alkaline comet assay. RESULTS: In general, concentrations of zinc, nickel, iron,
      and manganese were statistically higher in exposed individuals. A significant
      effect of the organ and the site on all metal tissue concentrations was detected.
      Significant DNA damage levels were registered in the exposed group, being higher
      in B. musculus. Females registered higher DNA damage levels than males. A
      negative relationship between distance from the mine tailing and DNA damage in B.
      musculus was observed. CONCLUSIONS: We consider that B. musculus is a suitable
      species to assess environmental quality, especially for bioaccumulable pollutants
      -such as metals--and recommend that it may be considered as a sentinel species.

PMID- 22161301
TI  - Aldosterone and the kidney.
AB  - The mineralocorticoid aldosterone is a key regulator of blood pressure, fluid and
      electrolyte homeostasis, and acts via the mineralocorticoid receptor (MR). In
      recent years, an increasing number of studies revealed deleterious effects of
      aldosterone via its receptor. Especially in patients with primary
      hyperaldosteronism (PHA) a significant higher risk of developing cardiovascular
      comorbidities and comortalities was reported. Also renal insufficiency is clearly
      increased in patients with PHA indicating a role of aldosterone and the MR in the
      pathogenesis of renal injury. It has been shown that aldosterone in combination
      with an elevated salt intake, leads to renal inflammation, fibrosis, podocyte
      injury, and mesangial cell proliferation. This review focuses on the current
      knowledge of aldosterone effects in the kidney and highlights this topic from 2
      perspectives: from clinical medicine and from experimental studies.

PMID- 22161300
TI  - Short-term effects of compost amendment on the fractionation of cadmium in soil
      and cadmium accumulation in rice plants.
AB  - PURPOSE: We used a sequential extraction to investigate the effects of compost
      amendment on Cd fractionation in soil during different incubation periods in
      order to assess Cd stabilization in soil over time. METHODS: Pot experiments
      using rice plants growing on Cd-spiked soils were carried out to evaluate the
      influence of compost amendment on plant growth and Cd accumulation by rice. Two
      agricultural soils (Pinchen and Lukang) of Taiwan were used for the experiments.
      The relationship between the redistribution of Cd fractions and the reduction of
      plant Cd concentration due to compost amendment was then investigated. RESULTS
      AND DISCUSSION: Compost amendment in Pinchen soil (lower pH) could transform
      exchangeable Cd into the Fe- and Mn-oxide-bound forms. With increasing incubation
      time, exchangeable Cd tended to transform into carbonate- and Fe- and Mn-oxide
      bound fractions. In Lukang soil (higher pH), carbonate- and Fe- and Mn-oxide
      bonded Cd were the main fractions. Exchangeable Cd was low. Compost amendment
      transformed the carbonate-bound form into the Fe and Mn oxide form. Pot
      experiments of rice plants showed that compost amendment enhanced plant growth
      more in Pinchen soil than in Lukang soil. Compost amendment could significantly
      reduce Cd accumulation in rice roots in both Pinchen and Lukang soils and
      restrict internal transport of Cd from the roots to the shoots. Because
      exchangeable Cd can be transformed into the stronger bonded fractions quickly in
      Pinchen soil, a reduction of Cd accumulation in rice due to compost amendment of
      Pinchen soil was significant by 45 days of growth. However, carbonate-bonded
      fractions in Lukang soil may provide a source of available Cd to rice plants, and
      exchangeable and carbonate-bonded fractions are transformed into the other
      fractions slowly. Thus, reduction of Cd accumulation by rice due to compost
      amendment in Lukang soil was significant by 75 days of growth. CONCLUSIONS: The
      results of the study suggest that the effectiveness of compost amendment used for
      stabilization of Cd and to decrease the phytoavailability of Cd for rice plants
      is different in acidic and alkaline soils. In acidic soil, Cd fractionation
      redistributes quickly after compost amendment and shows a significant reduction
      of Cd accumulation by the plant within a few weeks. In alkaline soil, due to the
      strongly bound fractions of Cd being in greater quantity than the weakly bound
      ones, a longer period (a few months) to redistribute Cd fractions is needed.

PMID- 22161302
TI  - Preparation of antioxidant peptide from egg white protein and improvement of its
      activities assisted by high-intensity pulsed electric field.
AB  - BACKGROUND: Egg white protein powder was hydrolyzed by three proteases-alcalase,
      trypsin, and pepsin-to produce antioxidant peptides. Three kinds of hydrolysates
      were prepared under optimal enzymatic parameters that were obtained from the
      preliminary one-factor-at-a-time test and response surface methodology.
      Thereafter, three enzymatic hydrolysates were sequentially fractionated by
      ultrafiltration membranes in cut-off MW of 30, 10, and 1 kDa, and tested in terms
      of their reducing power (RP). Effects of high-intensity pulsed electric field
      (PEF) were further investigated on the antioxidant peptides to improve their
      activities. RESULTS: Alcalase hydrolysates possessed stronger RP ability than the
      other two hydrolysates, particularly for the fraction within < 1 kDa. After PEF
      treatment, this fraction showed an improvement of RP ability within 4 h; however,
      the effects were reversible. High-performance liquid chromatographic analysis
      showed some MW changes of PEF-treated sample compared with control. CONCLUSIONS:
      Among the three kinds of proteases, alcalase could be regarded as the most
      appropriate enzyme for preparation of bioactive peptide from egg white protein,
      with the best antioxidant activity. Also, PEF showed some effects on the peptide
      and could be further applied to improve its antioxidant activity.

PMID- 22161303
TI  - Treatment of brain metastases: chemotherapy.
AB  - Although systemic therapy is the primary therapeutic modality for disseminated
      cancer, it plays a limited role in the treatment of brain metastases (BM). This
      review discusses the blood-brain barrier (BBB), interactions of systemic therapy
      with supportive care agents used in BM patients, the role of primary tumor
      sensitivity in the treatment of BM, and unique issues related to the specific
      primary tumor histologies. The specialized physiology of the brain vasculature
      that forms the BBB may preclude large and/or water-soluble systemic agents from
      reaching BM. Once metastases grow larger than 1-2 mm, there is preclinical and
      clinical evidence that the BBB is at least partially disrupted. Thus, the best
      treatment strategy in established BM may be to use an agent that is effective
      against the primary tumor regardless of its apparent BBB permeability. The use of
      anticonvulsants and corticosteroids must be carefully considered as they can
      decrease the effectiveness of systemic anti-tumor therapy. Despite the absence of
      level I data to routinely recommend the use of systemic therapy for solid tumor
      BM, these treatments should be considered in patients with good performance
      status and multiple, small metastases, especially if the primary tumor is
      chemosensitive. The systemic treatment of BM will continue to evolve as effective
      small-molecule inhibitors are developed and treatment regimens for each specific
      primary tumor are optimized.

PMID- 22161304
TI  - Data processing and analysis in real-world traditional Chinese medicine clinical
      data: challenges and approaches.
AB  - Traditional Chinese medicine (TCM) is a clinical-based discipline in which real
      world clinical practice plays a significant role for both the development of
      clinical therapy and theoretical research. The large-scale clinical data
      generated during the daily clinical operations of TCM provide a highly valuable
      knowledge source for clinical decision making. Secondary analysis of these data
      would be a vital task for TCM clinical studies before the randomised controlled
      trials are conducted. In this article, we discuss the challenges and issues, such
      as structured data curation, data preprocessing and quality, large-scale data
      management and complex data analysis requirements, in the data processing and
      analysis of real-world TCM clinical data. Furthermore, we also discuss related
      state-of-the-art research and solutions in China. We have shown that the clinical
      data warehouse based on the collection of structured electronic medical record
      data and clinical terminology would be a promising approach for generating
      clinical hypotheses and helping the discovery of clinical knowledge from large
      scale real-world TCM clinical data.

PMID- 22161305
TI  - Nematode-induced interference with the anti-Plasmodium CD8+ T-cell response can
      be overcome by optimizing antigen administration.
AB  - Malaria is still responsible for up to 1 million deaths per year worldwide,
      highlighting the need for protective malaria vaccines. Helminth infections that
      are prevalent in malaria endemic areas can modulate immune responses of the host.
      Here we show that Strongy-Ioides ratti, a gut-dwelling nematode that causes
      transient infections, did not change the efficacy of vaccination against
      Plasmodium berghei. An ongoing infection with Litomosoides sigmodontis, a tissue
      dwelling filaria that induces chronic infections in BALB/c mice, significantly
      interfered with vaccination efficacy. The induction of P. berghei circumspor
      ozoite protein (CSP)-specific CD8(+)  T cells, achieved by a single immunization
      with a CSP fusion protein, was diminished in L. sigmodontis-infected mice. This
      modulation was reflected by reduced frequencies of CSP-specific CD8(+)  T cells,
      reduced CSP-specific IFN-y and TNF-a production, reduced CSP-specific
      cytotoxicity, and reduced protection against P. berghei challenge infection.
      Implementation of a more potent vaccine regime, by first priming with CSP
      expressing recombinant live Salmonella prior to CSP fusion protein immunization,
      restored induction of CSP-specific CD8(+)  T cells and conferred almost sterile
      immunity to P. berghei challenge infection also in L. sigmodontis-infected mice.
      In summary, we show that appropriate vaccination regimes can overcome helminth
      induced interference with vaccination efficacy.

PMID- 22161306
TI  - Oxidative stress induced by aluminum oxide nanomaterials after acute oral
      treatment in Wistar rats.
AB  - This study investigated the oxidative stress induced after acute oral treatment
      with 500, 1000 and 2000 mg kg-1 doses of Al2O3 -30 and -40 nm and bulk Al2O3 in
      Wistar rats. Both the nanomaterials induced significant oxidative stress in a
      dose-dependent manner in comparison to the bulk. There was no significant
      difference between the two nanomaterials. However, the effect decreased with
      increase with time after treatment. The histopathological examination showed
      lesions only in liver with Al2O3 nanomaterials at 2000 mg kg-1.

PMID- 22161308
TI  - Prediction and in vitro evaluation of selected protease inhibitor antiviral drugs
      as inhibitors of carboxylesterase 1: a potential source of drug-drug
      interactions.
AB  - PURPOSE: To predict and determine whether the protease inhibitors (PIs)
      nelfinavir, amprenavir, atazanavir, ritonavir, and saquinavir could serve as
      metabolic inhibitors of the human CES1 (hCES1) using both molecular modeling
      techniques and in vitro inhibition assays. METHODS: Initially, a molecular
      modeling approach was utilized to predict whether the selected PIs could serve as
      hCES1 inhibitors. The inhibitory effects of these PIs on hCES1 activity were then
      further evaluated utilizing previously established in vitro assay. RESULTS:
      Pharmacophore and 2D-QSAR modeling predicted that nelfinavir would serve as a
      potent hCES1 inhibitor. This hypothesis was validated by in vitro hCES1
      inhibition studies. Other PIs (amprenavir, atazanavir, ritonavir, saquinavir)
      were evaluated and also shown to be hCES1 inhibitors in vitro, although
      substantially less potent relative to nelfinavir. CONCLUSION: Computational
      molecular modeling is a valid approach to identify potential hCES1 inhibitors as
      candidates for further assessment using validated in vitro techniques. DDIs could
      occur when nelfinavir is co-administered with drugs metabolized by hCES1.

PMID- 22161311
TI  - Is M65 really better than M30 as a biomarker of hepatic fibrosis?

PMID- 22161310
TI  - Investigation into the influence of primary crystallization conditions on the
      mechanical properties and secondary processing behaviour of fluticasone
      propionate for carrier based dry powder inhaler formulations.
AB  - PURPOSE: To investigate the influence of primary crystallization conditions on
      the mechanical properties and secondary processing behaviour of fluticasone
      propionate (FP) for carrier based dry powder inhaler (DPI) formulations. METHODS:
      Young's modulus of FP crystals produced using different anti-solvents was
      determined using nanoindentation. Physicochemical and surface interfacial
      properties via the cohesive-adhesive balance (CAB) approach to colloid probe
      atomic force microscopy (AFM) of air-jet micronised FP crystals were
      investigated. These data were correlated to in vitro aerosolization performance
      of binary and combination DPI formulations containing salmeterol xinafoate (SX).
      RESULTS: Young's modulus of FP crystals produced using different anti-solvents
      ranged from 0.6-12.4 GPa. Crystals with low Young's modulus required multiple
      passes in the microniser to reduce the particle size to less than 5 MUm, whilst
      those with the highest Young's modulus required a single pass. CAB of micronized
      FP samples was similar with respect to lactose, however, their adhesive affinity
      to SX varied. Samples of FP with greatest adhesion to SX produced greater fine
      particle delivery of SX in combination DPI formulations. CONCLUSIONS:
      Crystallisation conditions may affect the mechanical properties of FP, and
      therefore secondary processing of the material and their interfacial properties
      and product performance in carrier based DPI formulations.

PMID- 22161312
TI  - Combined proteomic and molecular approaches for cloning and characterization of
      copper-zinc superoxide dismutase (Cu, Zn-SOD2) from garlic (Allium sativum).
AB  - Superoxide dismutases (SODs; EC 1.15.1.1) are key enzymes in the cells protection
      against oxidant agents. Thus, SODs play a major role in the protection of aerobic
      organisms against oxygen-mediated damages. Three SOD isoforms were previously
      identified by zymogram staining from Allium sativum bulbs. The purified Cu, Zn
      SOD2 shows an antagonist effect to an anticancer drug and alleviate cytotoxicity
      inside tumor cells lines B16F0 (mouse melanoma cells) and PAE (porcine aortic
      endothelial cells). To extend the characterization of Allium SODs and their
      corresponding genes, a proteomic approach was applied involving two-dimensional
      gel electrophoresis and LC-MS/MS analyses. From peptide sequence data obtained by
      mass spectrometry and sequences homologies, primers were defined and a cDNA
      fragment of 456 bp was amplified by RT-PCR. The cDNA nucleotide sequence analysis
      revealed an open reading frame coding for 152 residues. The deduced amino acid
      sequence showed high identity (82-87%) with sequences of Cu, Zn-SODs from other
      plant species. Molecular analysis was achieved by a protein 3D structural model.

PMID- 22161313
TI  - ENAC1, a NAC transcription factor, is an early and transient response regulator
      induced by abiotic stress in rice (Oryza sativa L.).
AB  - The plant-specific NAC (NAM, ATAF, and CUC)-domain proteins play important roles
      in plant development and stress responses. In this research, a full-length cDNA
      named ENAC1 (early NAC-domain protein induced by abiotic stress 1) was isolated
      from rice. ENAC1 possess one NAC domain in the N-terminus. Comparative time
      course expression analysis indicated that ENAC1 expression, similar with
      OsDREB1A, was induced very quickly by various abiotic stresses including salt,
      drought, cold, and exogenous abscisic acid. However, the induction of ENAC1 by
      abiotic stress was transient and lasted up to 3 h, whereas that of OsDREB1A
      maintained longer. The promoter sequence of ENAC1 harbors several cis-elements
      including ABA response elements, but the well-known dehydration responsive
      element/C-repeat element is absent. The ENAC1-GFP (green fluorescent protein)
      fusion protein was localized in the nucleus of rice protoplast cell. Yeast hybrid
      assays revealed that ENAC1 was a transcription activator and bound to NAC
      recognition sequence (NACRS). Co-expression analysis suggested that ENAC1 co
      expressed with a number of stress-related genes. Taken together, ENAC1 may be an
      early transcription activator of stress responses and function in the regulation
      of NACRS-mediated gene expression under abiotic stress.

PMID- 22161314
TI  - Effects of zinc supplementation on the element distribution in kidney tissue of
      diabetic rats subjected to acute swimming.
AB  - In this study, we report the effect of zinc supplementation on the distribution
      of elements in kidney tissue of diabetic rats subjected to acute swimming
      exercise. Diabetes was induced by two subcutaneous injections of 40 mg/kg of
      streptozotocin within a 24-h period. Zinc was given intraperitoneally at a dose
      of 6 mg/kg per day for a period of 4 weeks. The rats (n = 80) were equally
      divided into eight study groups: controls, zinc-supplemented, swimming, diabetic,
      zinc-supplemented diabetic, zinc-supplemented swimming, diabetic swimming, and
      zinc-supplemented diabetic swimming. The levels of lead, cobalt, molybdenum,
      chromium, boron, magnesium, iron, copper, calcium, zinc, and selenium were
      determined in the kidney tissue samples by ICP-AES. Higher molybdenum, calcium,
      zinc, and selenium values were found in both swimming and nonswimming diabetic
      rats. Significantly higher iron values were found in swimming, diabetic, diabetic
      swimming, and zinc-supplemented diabetic swimming rats (p < 0.001). Diabetic,
      zinc-supplemented diabetic, diabetic swimming, and zinc-supplemented diabetic
      swimming rats had the highest copper values. These results show that zinc
      supplementation normalized the higher levels of molybdenum, calcium, selenium,
      and iron levels seen in diabetic rats, indicating that zinc may have a regulatory
      effect on element metabolism in kidney tissue.

PMID- 22161307
TI  - Immune mediated diseases and immune modulation in the neurocritical care unit.
AB  - This chapter will review the spectrum of immune-mediated diseases that affect the
      nervous system and may result in an admission to the neurological intensive care
      unit. Immunomodulatory strategies to treat acute exacerbations of neurological
      diseases caused by aberrant immune responses are discussed, but strategies for
      long-term immunosuppression are not presented. The recommendations for
      therapeutic intervention are based on a synthesis of the literature, and include
      recommendations by the Cochrane Collaborative, the American Academy of Neurology,
      and other key organizations. References from recent publications are provided for
      the disorders and therapies in which randomized clinical trials and large
      evidenced-based reviews do not exist. The chapter concludes with a brief review
      of the mechanisms of action, dosing, and side effects of commonly used
      immunosuppressive strategies in the neurocritical care unit.

PMID- 22161315
TI  - Using the pollen viability and morphology for fluoride pollution biomonitoring.
AB  - The methods using plants for biomonitoring of air and soil quality are simple,
      cheap, and fast and can supplement the classical physicochemical methods. In this
      study, biological pollen characterization of some collected legume species from
      an aluminum smelter area in Iran (IRALCO) was carried out to determine the actual
      value of pollen as a bioindicator of the effects of soil and atmospheric
      pollution. Young buds and flowers of six legumes (Cercis siliquastrum L.,
      Medicago sativa L., Robinia pseudoacacia L., Melilotus officinalis (L.) lam,
      Trifolium repens L., and Sophora alopecuroides L.) in polluted and control plants
      were removed and compared. Studies of light and electron microscopic preparation
      showed some abnormalities during pollen development in affect of fluoride
      pollution. The viability of pollen grains estimated by staining with acetocarmine
      shows sharp differences in smearing advanced pollen grains from abnormal ones.
      Except M. officinalis, the pollen grains of C. siliquastrum, M. sativa, R.
      pseudoacacia, T. repens, and S. alopecuroides in polluted areas showed light,
      partial, or no staining with acetocarmine, whereas almost all of the control ones
      clearly stained. Observation of the pollen grains by light microscopy and
      scanning electron microscopy showed the significant effect of fluoride on shapes
      and sizes of pollen grains. The stimulation and inhibition of these pollen
      characteristics depend on the pollen species as well as on the pollutant and its
      concentration. Therefore, pollen grains provide essential information on
      biological impact of pollutants and they are good candidates for biomonitoring
      the atmospheric and edaphic pollutions.

PMID- 22161316
TI  - Determination of mineral elements in Gentiana rigescens from different zones of
      Yunnan, China.
AB  - The concentrations of nine mineral elements were determined by atomic absorption
      spectroscopy in Gentiana rigescens from three zones (middle, southeast, and
      northwest zones) of Yunnan province in China. The average concentrations of
      mineral elements were found in the order K>Ca>Mg>Fe>Na>Zn>Cu>Cr>Se. Samples
      collected from the middle zone of Yunnan were enriched in Na (242.24 +/- 50.80
      mg/kg) and Mg (959.78 +/- 54.60 mg/kg). However, materials from the southeast
      zone were particularly enriched in Ca (3,448.70 +/- 749.82 mg/kg), but depleted
      in Se. Whereas those from the northwest zone were plentiful of K (2,746.89 +/-
      84.84 mg/kg), Fe (923.06 +/- 127.52 mg/kg), Zn (261.38 +/- 53.05 mg/kg), Cu
      (110.08 +/- 46.23 mg/kg), and Se (53.99 +/- 22.38 mg/kg).

PMID- 22161317
TI  - Improving quality through clinical risk management: a triage sentinel event
      analysis.
AB  - "Triage" is a useful tool used in emergency departments (EDs) to prioritize the
      care of patients. Through a methodical process of different sequential steps, the
      triage nurse assigns a color code which goes from red-critical patient with
      immediate access to medical examination-to a white code that represents no
      urgency. Clinical studies have shown that patients can be victims of errors
      during the process of care, especially in complex systems such as EDs. To reduce
      errors it is essential to map the risks in order to identify the causes (both
      individual and organizational); the introduction of corrective changes cannot be
      postponed. The incorrect assessment at triage represents one of the major errors
      in EDs. By monitoring this activity, through the analysis of sentinel events we
      can reduce adverse consequences. Missed recognition of a red code indicates a
      sentinel event. We used a "root cause analysis" to explain an episode of missed
      recognition of red code at triage. A nurse without specific training in triage
      and inexperienced in critical care was identified as the "root cause" of the
      sentinel event. To make improvements we planned a triage training course (for
      newly employed nurses and a refresher course for existing staff) and created a
      team of dedicated triage nurses.

PMID- 22161318
TI  - Cardiovascular toxicity of anticancer-targeted therapy: emerging issues in the
      era of cardio-oncology.
AB  - Over the last decade, the advent of molecular targeted therapy radically changed
      the treatment of several forms of cancer. However, these innovative anticancer
      drugs, namely monoclonal antibodies and small molecule tyrosine kinase inhibitors
      were found to adversely affect cardiovascular function. These "on-target" and
      "off-target" drug side effects encompass a wide range of cardio toxicities,
      including left ventricular dysfunction leading to heart failure,
      electrocardiographic abnormalities with dysrhythmias, hypertension, myocardial
      ischemia and thromboembolic events. The unclear incidence of drug-induced
      cardiovascular events together with uncertainty on their reversibility and long
      term safety call for a multidisciplinary effort embracing cardio-oncological
      expertise supported by primary care physicians, pharmacologists and
      toxicologists. Here we address emerging cardiovascular events associated with
      targeted anticancer drugs by offering a concise review on: (1) mechanistic basis
      subtending cardiotoxicity and (2) clinical advice for effective patient
      management (i.e., detection, treatment, monitoring and reporting of
      cardiovascular side effects). In this scenario, onco-vigilance (i.e.,
      pharmacovigilance oriented to oncologic drugs) is emerging as a key to support
      cardio-oncologists in appropriateness [corrected].

PMID- 22161320
TI  - Modular analysis of biological networks.
AB  - The analysis of complex biological networks has traditionally relied on
      decomposition into smaller, semi-autonomous units such as individual signaling
      pathways. With the increased scope of systems biology (models), rational
      approaches to modularization have become an important topic. With increasing
      acceptance of de facto modularity in biology, widely different definitions of
      what constitutes a module have sparked controversies. Here, we therefore review
      prominent classes of modular approaches based on formal network representations.
      Despite some promising research directions, several important theoretical
      challenges remain open on the way to formal, function-centered modular
      decompositions for dynamic biological networks.

PMID- 22161319
TI  - Matrix metalloproteinases in cytotoxic lymphocytes impact on tumour infiltration
      and immunomodulation.
AB  - To efficiently combat solid tumours, endogenously or adoptively transferred
      cytotoxic T cells and natural killer (NK) cells, need to leave the vasculature,
      traverse the interstitium and ultimately infiltrate the tumour mass. During this
      locomotion and migration in the three dimensional environment many obstacles need
      to be overcome, one of which is the possible impediment of the extracellular
      matrix. The first and obvious one is the sub-endothelial basement membrane but
      the infiltrating cells will also meet other, both loose and tight, matrix
      structures that need to be overridden. Matrix metalloproteinases (MMPs) are
      believed to be one of the most important endoprotease families, with more than 25
      members, which together have function on all known matrix components. This review
      summarizes what is known on synthesis, expression patterns and regulation of MMPs
      in cytotoxic lymphocytes and their possible role in the process of tumour
      infiltration. We also discuss different functions of MMPs as well as the possible
      use of other lymphocyte proteases for matrix degradation.

PMID- 22161321
TI  - Modeling signaling networks using high-throughput phospho-proteomics.
AB  - Cellular communication and information processing is performed by complex,
      dynamic, and context specific signaling networks. Mathematical modeling is a very
      useful tool to make sense of this complexity. Building a model relies on two main
      ingredients: data and an adequate model formalism. In the case of signaling
      networks, we build mainly upon data at the proteome level, in particular about
      the phosphorylation of proteins. In this chapter we review recent developments in
      both data acquisition and computational analysis. We describe two approaches,
      antibody based technologies and mass spectrometry (MS), along with their main
      features and limitations. We then go on to describe some model formalisms that
      have been applied to such high-throughput phospho-proteomics data sets. We
      consider a variety of formalisms from clustering and data mining approaches to
      differential equation-based mechanistic models, rule-based, and logic based
      models, and on through Bayesian network inference and linear regressions.

PMID- 22161322
TI  - An integrated Bayesian framework for identifying phosphorylation networks in
      stimulated cells.
AB  - One of the primary mechanisms of signal transduction in cells is protein
      phosphorylation. Upon ligand stimulation a series of phosphorylation events take
      place which eventually lead to transcription. Different sets of phosphorylation
      events take place due to different stimulating ligands in different types of
      cells. Knowledge of these phosphorylation events is essential to understand the
      underlying signaling mechanisms. We have developed a Bayesian framework to infer
      phosphorylation networks from time series measurements of phosphosite
      concentrations upon ligand stimulation. To increase the prediction accuracy we
      integrated different types of data, e.g., amino acid sequence data, genomic
      context data (gene fusion, gene neighborhood, and phylogentic profiles), primary
      experimental evidence (physical protein interactions and gene coexpression),
      manually curated pathway databases, and automatic literature mining with time
      series data in our inference framework. We compared our results with data
      available from public databases and report a high level of prediction accuracy.

PMID- 22161323
TI  - Signaling cascades: consequences of varying substrate and phosphatase levels.
AB  - We study signaling cascades with an arbitrary number of layers of one-site
      phosphorylation cycles. Such cascades are abundant in nature and integrated parts
      of many pathways. Based on the Michaelis-Menten model of enzyme kinetics and the
      law of mass-action, we derive explicit analytic expressions for how the steady
      state concentrations and the total amounts of substrates, kinase, and
      phosphatates depend on each other. In particular, we use these to study how the
      responses (the activated substrates) vary as a function of the available amounts
      of substrates, kinase, and phosphatases. Our results provide insight into how the
      cascade response is affected by crosstalk and external regulation.

PMID- 22161324
TI  - Heterogeneous biological network visualization system: case study in context of
      medical image data.
AB  - We have developed a system called megNet for integrating and visualizing
      heterogeneous biological data in order to enable modeling biological phenomena
      using a systems approach. Herein we describe megNet, including a recently
      developed user interface for visualizing biological networks in three dimensions
      and a web user interface for taking input parameters from the user, and an in
      house text mining system that utilizes an existing knowledge base. We demonstrate
      the software with a case study in which we integrate lipidomics data acquired in
      house with interaction data from external databases, and then find novel
      interactions that could possibly explain our previous associations between
      biological data and medical images. The flexibility of megNet assures that the
      tool can be applied in diverse applications, from target discovery in medical
      applications to metabolic engineering in industrial biotechnology.

PMID- 22161325
TI  - Evolution of the cognitive proteome: from static to dynamic network models.
AB  - Integrative analysis of the neuronal synapse proteome has uncovered an
      evolutionarily conserved signalling complex that underpins the cognitive
      capabilities of the brain. Highly dynamic, cell type specific and intricately
      regulated, the synaptic proteome presents many challenges to systems biology
      approaches, yet this is likely to be the best route to unlock a new generation of
      neuroscience research and CNS drug development that society so urgently demands.
      Most systems biology approaches today have focussed on exploiting protein-protein
      interaction data to their fullest extent within static interaction models. These
      have revealed structure-function relationships within the protein network,
      uncovered new candidate genes for genetic studies and drug research and
      development and finally provided a means to study the evolution of the system.
      The rapid maturation of medium and high-throughput biochemical technologies means
      that dissecting the synapse proteome's dynamic complexity is fast becoming a
      reality. Here we look at these new challenges and explore rule-based modelling as
      a basis for a new generation of synaptic models.

PMID- 22161326
TI  - Molecular systems biology of Sic1 in yeast cell cycle regulation through
      multiscale modeling.
AB  - Cell cycle control is highly regulated to guarantee the precise timing of events
      essential for cell growth, i.e., DNA replication onset and cell division. Failure
      of this control plays a role in cancer and molecules called cyclin-dependent
      kinase (Cdk) inhibitors (Ckis) exploit a critical function in cell cycle timing.
      Here we present a multiscale modeling where experimental and computational
      studies have been employed to investigate structure, function and temporal
      dynamics of the Cki Sic1 that regulates cell cycle progression in Saccharomyces
      cerevisiae. Structural analyses reveal molecular details of the interaction
      between Sic1 and Cdk/cyclin complexes, and biochemical investigation reveals Sic1
      function in analogy to its human counterpart p27(Kip1), whose deregulation leads
      to failure in timing of kinase activation and, therefore, to cancer. Following
      these findings, a bottom-up systems biology approach has been developed to
      characterize modular networks addressing Sic1 regulatory function. Through
      complementary experimentation and modeling, we suggest a mechanism that underlies
      Sic1 function in controlling temporal waves of cyclins to ensure correct timing
      of the phase-specific Cdk activities.

PMID- 22161327
TI  - Proteome-wide screens in Saccharomyces cerevisiae using the yeast GFP collection.
AB  - The budding yeast is a simple and genetically tractable eukaryotic organism. It
      remains a leading system for functional genomic work and has been the focus of
      many pioneering efforts, including the systematic construction and analysis of
      gene deletion mutants. Over the past decade, many large-scale studies have made
      use of the deletion and other mutant collections to assay genetic interactions,
      chemical sensitivities, and other phenotypes, contributing enormously to our
      understanding of gene function. The deletion mutant collection has also been used
      in cell biological surveys to identify genes that control cell and organelle
      morphology. One valuable approach for systematic definition of gene function and
      biological pathways involves global assessment of the localization patterns of
      the proteins they encode and how these patterns are altered in response to
      environmental or genetic perturbation. However, proteome-wide, cell biological
      screens are extremely challenging, from both a technical and computational
      perspective. The yeast GFP collection, an elegant and unique strain set, is ideal
      for studying both protein localization and abundance across the proteome (
      http://yeastgfp.yeastgenome.org/ ). In this chapter, we outline how the yeast GFP
      collection has been used to date and discuss approaches for conducting future
      surveys of the proteome.

PMID- 22161329
TI  - The cell as a thermostat: how much does it know?
AB  - How does bacterial thermotaxis compare to a simple wall thermostat? Elements with
      similar function can be found in the two, including a temperature-sensing
      element, an output switch, and an external control. But they differ in their
      origins. A thermostat is designed and made by humans and embodies their
      understanding of seasonal fluctuations in temperature and how these affect room
      comfort. By contrast, the bacterial system is self-contained and assembles
      according to information in its genome acquired by evolution. This information is
      far richer than anything carried by a thermostat and closer to the 'knowledge'
      that higher animals have about the world.

PMID- 22161328
TI  - Unraveling the complex regulatory relationships between metabolism and signal
      transduction in cancer.
AB  - Cancer cells exhibit an altered metabolic phenotype, known as the Warburg effect,
      which is characterized by high rates of glucose uptake and glycolysis, even under
      aerobic conditions. The Warburg effect appears to be an intrinsic component of
      most cancers and there is evidence linking cancer progression to mutations,
      translocations, and alternative splicing of genes that directly code for or have
      downstream effects on key metabolic enzymes. Many of the same signaling pathways
      are routinely dysregulated in cancer and a number of important oncogenic
      signaling pathways play important regulatory roles in central carbon metabolism.
      Unraveling the complex regulatory relationship between cancer metabolism and
      signaling requires the application of systems biology approaches. Here we discuss
      computational approaches for modeling protein signal transduction and metabolism
      as well as how the regulatory relationship between these two important cellular
      processes can be combined into hybrid models.

PMID- 22161330
TI  - Stem cell differentiation as a renewal-reward process: predictions and validation
      in the colonic crypt.
AB  - Stem cells serve as persistent reservoirs for replenishment of rapidly renewing
      tissues, frequently also ensuring that the correct tissue morphology is
      maintained. This process is inherently stochastic due to the small number and
      stochastic division patterns within the stem cell compartments, as well as the
      essentially stochastic differentiation events that follow the initial stem cell
      expansion. Here we propose a new formalism to describe this process, by employing
      the approach known in statistics as the renewal-reward process. Using this
      approximation allows application of the mathematical apparatus developed for
      renewal-reward processes to the stochastic stem cell biology. We show in the
      context of colonic crypts that the resulting predictions match the experimental
      results, while also providing a convenient tool for analysis of normal and
      abnormal differentiation processes.

PMID- 22161331
TI  - A dynamic physical model of cell migration, differentiation and apoptosis in
      Caenorhabditis elegans.
AB  - The germ line of the nematode C. elegans provides a paradigm to study essential
      developmental concepts like stem cell differentiation and apoptosis. Here, we
      have created a computational model encompassing these developmental landmarks and
      the resulting movement of germ cells along the gonadal tube. We have used a
      technique based on molecular dynamics (MD) to model the physical movement of
      cells solely based on the force that arises from dividing cells. This novel way
      of using MD to drive the model enables calibration of simulation and experimental
      time. Based on this calibration, the analysis of our model shows that it is in
      accordance with experimental observations. In addition, the model provides
      insights into kinetics of molecular pathways within individual cells as well as
      into physical aspects like the cell density along the germ line and in local
      neighbourhoods of individual germ cells. In the future, the presented model can
      be used to test hypotheses about diverse aspects of development like stem cell
      division or programmed cell death. An iterative process of evolving this model
      and experimental testing in the model system C. elegans will provide new insights
      into key developmental aspects.

PMID- 22161332
TI  - A modular model of the apoptosis machinery.
AB  - Using a modular principle of computer hardware as a metaphor, we defined and
      implemented in the BioUML platform a module concept for biological pathways.
      BioUML provides a user interface to create modular models and convert them
      automatically into plain models for further simulations. Using this approach, we
      created the apoptosis model including 13 modules: death stimuli (TRAIL, CD95L,
      and TNF-alpha)-induced activation of caspase-8; survival stimuli (p53, EGF, and
      NF-kappaB) regulation; the mitochondria level; cytochrome C- and Smac-induced
      activation of caspase-3; direct activation of effector caspases by caspase-8 and 
      12; PARP and apoptosis execution phase modules. Each module is based on earlier
      published models and extended by data from the Reactome and TRANSPATH databases.
      The model ability to simulate the apoptosis-related processes was checked; the
      modules were validated using experimental data. AVAILABILITY:
      http://www.biouml.org/apoptosis.shtml .

PMID- 22161333
TI  - An ensemble approach for inferring semi-quantitative regulatory dynamics for the
      differentiation of mouse embryonic stem cells using prior knowledge.
AB  - The process of differentiation of embryonic stem cells (ESCs) is currently
      becoming the focus of many systems biologists not only due to mechanistic
      interest but also since it is expected to play an increasingly important role in
      regenerative medicine, in particular with the advert to induced pluripotent stem
      cells. These ESCs give rise to the formation of the three germ layers and
      therefore to the formation of all tissues and organs. Here, we present a
      computational method for inferring regulatory interactions between the genes
      involved in ESC differentiation based on time resolved microarray profiles. Fully
      quantitative methods are commonly unavailable on such large-scale data; on the
      other hand, purely qualitative methods may fail to capture some of the more
      detailed regulations. Our method combines the beneficial aspects of qualitative
      and quantitative (ODE-based) modeling approaches searching for quantitative
      interaction coefficients in a discrete and qualitative state space. We further
      optimize on an ensemble of networks to detect essential properties and compare
      networks with respect to robustness. Applied to a toy model our method is able to
      reconstruct the original network and outperforms an entire discrete boolean
      approach. In particular, we show that including prior knowledge leads to more
      accurate results. Applied to data from differentiating mouse ESCs reveals new
      regulatory interactions, in particular we confirm the activation of Foxh1 through
      Oct4, mediating Nodal signaling.

PMID- 22161334
TI  - Cell death and life in cancer: mathematical modeling of cell fate decisions.
AB  - Tumor development is characterized by a compromised balance between cell life and
      death decision mechanisms, which are tightly regulated in normal cells.
      Understanding this process provides insights for developing new treatments for
      fighting with cancer. We present a study of a mathematical model describing
      cellular choice between survival and two alternative cell death modalities:
      apoptosis and necrosis. The model is implemented in discrete modeling formalism
      and allows to predict probabilities of having a particular cellular phenotype in
      response to engagement of cell death receptors. Using an original parameter
      sensitivity analysis developed for discrete dynamic systems, we determine
      variables that appear to be critical in the cellular fate decision and discuss
      how they are exploited by existing cancer therapies.

PMID- 22161335
TI  - Theoretical aspects of cellular decision-making and information-processing.
AB  - Microscopic biological processes have extraordinary complexity and variety at the
      sub-cellular, intra-cellular, and multi-cellular levels. In dealing with such
      complex phenomena, conceptual and theoretical frameworks are crucial, which
      enable us to understand seemingly different intra- and inter-cellular phenomena
      from unified viewpoints. Decision-making is one such concept that has attracted
      much attention recently. Since a number of cellular behavior can be regarded as
      processes to make specific actions in response to external stimuli, decision
      making can cover and has been used to explain a broad range of different cellular
      phenomena [Balazsi et al. (Cell 144(6):910, 2011), Zeng et al. (Cell 141(4):682,
      2010)]. Decision-making is also closely related to cellular information
      processing because appropriate decisions cannot be made without exploiting the
      information that the external stimuli contain. Efficiency of information
      transduction and processing by intra-cellular networks determines the amount of
      information obtained, which in turn limits the efficiency of subsequent decision
      making. Furthermore, information-processing itself can serve as another concept
      that is crucial for understanding of other biological processes than decision
      making. In this work, we review recent theoretical developments on cellular
      decision-making and information-processing by focusing on the relation between
      these two concepts.

PMID- 22161336
TI  - Zooming in on yeast osmoadaptation.
AB  - Saccharomyces cerevisiae is considered as a model organism for the investigation
      of cellular and molecular processes and gene regulation. Specifically, the
      response of S. cerevisiae to increase in osmolarity of the external medium
      (osmoadaptation) is a model adaptation process. The first mathematical model of
      volume changes in S. cerevisiae due to osmolarity has been proposed as early as
      1983 by Schwartz and Diller (Cryobiology 20(5):542-552). Since then, both
      experimental and computational methods in biology have progressed dramatically.
      Especially in recent years, the study of response to hyperosmotic stress in S.
      cerevisiae by systems biology approaches has advanced rapidly. However, a
      holistic understanding of osmoadaptation combining environmental conditions,
      cellular preconditions, biophysical processes, molecular and biochemical network
      dynamics, has not yet been reached. Here, we review recent advances in the
      investigation of different aspects of osmoadaptation and discuss them with
      respect to an integrated view. This leads us to critically evaluate how to
      approach the goal of such an integrated view.

PMID- 22161337
TI  - Receptor dynamics in signaling.
AB  - Reliable inter- and intracellular communication is central to both the
      development and the integrity of multicellular organisms. Key mediators of these
      processes are cell surface receptors that perceive and convert extracellular cues
      to trigger intracellular signaling networks and ultimately a phenotypic response.
      Deregulation of signal transduction leads to a variety of diseases, and
      aberrations in receptor proteins are very common in various cancer types.
      Therefore, cell surface receptors have been established as major targets in drug
      discovery. However, in order to efficiently apply therapeutics, it is crucial to
      gain knowledge about design principles of receptor signaling. In this chapter, we
      will discuss signal transduction at the receptor level for examples from
      different receptor classes.

PMID- 22161339
TI  - Modeling morphodynamic phenotypes and dynamic regimes of cell motion.
AB  - Many cellular processes and signaling pathways converge onto cell morphology and
      cell motion, which share important components. The mechanisms used for propulsion
      could also be responsible for shape changes, if they are capable of generating
      the rich observed variety of dynamic regimes. Additionally, the analysis of cell
      shape changes in space and time promises insight into the state of the
      cytoskeleton and signaling pathways controlling it. While this has been obvious
      for some time by now, little effort has been made to systematically and
      quantitatively explore this source of information. First pioneering experimental
      work revealed morphodynamic phenotypes which can be associated with dynamic
      regimes like oscillations and excitability. Here, we review the current state of
      modeling of morphodynamic phenotypes, the experimental results and discuss the
      ideas on the mechanisms driving shape changes which are suggested by modeling.

PMID- 22161338
TI  - A systems-biology approach to yeast actin cables.
AB  - We focus on actin cables in yeast as a model system for understanding
      cytoskeletal organization and the workings of actin itself. In particular, we
      highlight quantitative approaches on the kinetics of actin-cable assembly and
      methods of measuring their morphology by image analysis. Actin cables described
      by these studies can span greater lengths than a thousand end-to-end actin
      monomers. Because of this difference in length scales, control of the actin-cable
      system constitutes a junction between short-range interactions - among actin
      monomers and nucleating, polymerization-facilitating, side-binding, severing, and
      cross-linking proteins - and the emergence of cell-scale physical form as
      embodied by the actin cables themselves.

PMID- 22161340
TI  - Time-structure of the yeast metabolism in vivo.
AB  - All previous studies on the yeast metabolome have yielded a plethora of
      information on the components, function and organisation of low molecular mass
      and macromolecular components involved in the cellular metabolic network. Here we
      emphasise that an understanding of the global dynamics of the metabolome in vivo
      requires elucidation of the temporal dynamics of metabolic processes on many time
      scales. We illustrate this using the 40 min oscillation in respiratory activity
      displayed in auto-synchronous continuously grown cultures of Saccharomyces
      cerevisiae, where respiration cycles between a phase of increased respiration
      (oxidative phase) and decreased respiration (reductive phase). Thereby an
      ultradian clock, i.e. a timekeeping device that runs through many cycles during
      one day, is involved in the co-ordination of the vast majority of events and
      processes in yeast. Through continuous online measurements, we first show that
      mitochondrial and redox physiology are intertwined to produce the temporal
      landscape on which cellular events occur. Next we look at the higher order
      processes of DNA duplication and mitochondrial structure to reveal that both
      events are choreographed during the respiratory cycles. Furthermore, spectral
      analysis using the discrete Fourier transformation of high-resolution (10 Hz)
      time-series of NAD(P)H confirms the existence of higher frequency components of
      biological origin and that these follow a scale-free architecture even in stable
      oscillating modes. A different signal-processing approach using discrete wavelet
      transformations (DWT) indicates that there is a significant contribution to the
      overall signal from ' ~5, ~ 10 and ~ 20-minutes cycles and the amplitudes of
      these cycles are phase-dependent. Further investigation (derivative of Gaussian
      continuous wavelet transformation) reveals that the observed 20-minutes cycles
      are actually confined to the reductive phase and consist of two ~15-minutes
      cycles. Moreover, the 5 and 10-minutes cycles are restricted to the oxidative
      phase of the cycle. The mitochondrial origin of these signals was confirmed by
      pulse-injection of the cytochrome c oxidase inhibitor H(2)S. We next discuss how
      these multi-oscillatory states can impinge on the apparently complex reactome
      (represented as a phase diagram of 1,650 chemical species that show oscillatory
      behaviour). We conclude that biological processes can be considerably more
      comprehensible when dynamic in vivo time-structure is taken into account.

PMID- 22161341
TI  - Coarse graining Escherichia coli chemotaxis: from multi-flagella propulsion to
      logarithmic sensing.
AB  - Various sensing mechanisms in nature can be described by the Weber-Fechner law
      stating that the response to varying stimuli is proportional to their relative
      rather than absolute changes. The chemotaxis of bacteria Escherichia coli is an
      example where such logarithmic sensing enables sensitivity over large range of
      concentrations. It has recently been experimentally demonstrated that under
      certain conditions E. coli indeed respond to relative gradients of ligands. We
      use numerical simulations of bacteria in food gradients to investigate the limits
      of validity of the logarithmic behavior. We model the chemotactic signaling
      pathway reactions, couple them to a multi-flagella model for propelling and take
      the effects of rotational diffusion into account to accurately reproduce the
      experimental observations of single cell swimming. Using this simulation scheme
      we analyze the type of response of bacteria subject to exponential ligand
      profiles and identify the regimes of absolute gradient sensing, relative gradient
      sensing, and a rotational diffusion dominated regime. We explore dependance of
      the swimming speed, average run time and the clockwise (CW) bias on ligand
      variation and derive a small set of relations that define a coarse grained model
      for bacterial chemotaxis. Simulations based on this coarse grained model compare
      well with microfluidic experiments on E. coli diffusion in linear and exponential
      gradients of aspartate.

PMID- 22161342
TI  - Self-feedback in actin polymerization.
AB  - Polymerization of actin, which is crucial for functions such as cell migration,
      membrane ruffling, cytokinesis, and endocytosis, must be tightly regulated in
      order to preserve an adequate supply of free actin monomers to respond to
      changing external conditions. The paper will describe mechanisms by which F-actin
      feeds back on its own assembly, thus regulating itself. I will present the
      experimental evidence for such feedback terms, discuss their use in current
      models of actin dynamics in cells, and present preliminary calculations for the
      role of feedback in transient endocytic actin patches. These calculations suggest
      a partial homeostasis of F-actin, in which the F-actin peak height depends only
      weakly on the actin filament nucleation rate.

PMID- 22161343
TI  - Global optimization in systems biology: stochastic methods and their
      applications.
AB  - Mathematical optimization is at the core of many problems in systems biology: (1)
      as the underlying hypothesis for model development, (2) in model identification,
      or (3) in the computation of optimal stimulation procedures to synthetically
      achieve a desired biological behavior. These problems are usually formulated as
      nonlinear programing problems (NLPs) with dynamic and algebraic constraints.
      However the nonlinear and highly constrained nature of systems biology models,
      together with the usually large number of decision variables, can make their
      solution a daunting task, therefore calling for efficient and robust optimization
      techniques. Here, we present novel global optimization methods and software tools
      such as cooperative enhanced scatter search (eSS), AMIGO, or DOTcvpSB, and
      illustrate their possibilities in the context of modeling including model
      identification and stimulation design in systems biology.

PMID- 22161344
TI  - Mathematical modeling of the human energy metabolism based on the Selfish Brain
      Theory.
AB  - Deregulations in the human energy metabolism may cause diseases such as obesity
      and type 2 diabetes mellitus. The origins of these pathologies are fairly
      unknown. The key role of the brain is the regulation of the complex whole body
      energy metabolism. The Selfish Brain Theory identifies the priority of brain
      energy supply in the competition for available energy resources within the
      organism. Here, we review mathematical models of the human energy metabolism
      supporting central aspects of the Selfish Brain Theory. First, we present a
      dynamical system modeling the whole body energy metabolism. This model takes into
      account the two central control mechanisms of the brain, i.e., allocation and
      appetite. Moreover, we present mathematical models of regulatory subsystems. We
      examine a neuronal model which specifies potential elements of the brain to sense
      and regulate cerebral energy content. We investigate a model of the HPA system
      regulating the allocation of energy within the organism. Finally, we present a
      robust modeling approach of appetite regulation. All models account for a
      systemic understanding of the human energy metabolism and thus do shed light onto
      defects causing metabolic diseases.

PMID- 22161345
TI  - Identification of sensitive enzymes in the photosynthetic carbon metabolism.
AB  - Understanding and optimizing the CO(2) fixation process would allow human beings
      to address better current energy and biotechnology issues. We focused on modeling
      the C(3) photosynthetic Carbon metabolism pathway with the aim of identifying the
      minimal set of enzymes whose biotechnological alteration could allow a functional
      re-engineering of the pathway. To achieve this result we merged in a single
      powerful pipe-line Sensitivity Analysis (SA), Single- (SO) and Multi-Objective
      Optimization (MO), and Robustness Analysis (RA). By using our recently developed
      multipurpose optimization algorithms (PAO and PMO2) here we extend our work
      exploring a large combinatorial solution space and most importantly, here we
      present an important reduction of the problem search space. From the initial
      number of 23 enzymes we have identified 11 enzymes whose targeting in the C(3)
      photosynthetic Carbon metabolism would provide about 90% of the overall
      functional optimization. Both in terms of maximal CO(2) Uptake and minimal
      Nitrogen consumption, these 11 sensitive enzymes are confirmed to play a key
      role. Finally we present a RA to confirm our findings.

PMID- 22161346
TI  - Formal methods for checking the consistency of biological models.
AB  - Formal modeling approaches such as process algebras and Petri nets seek to
      provide insight into biological processes by using both symbolic and numerical
      methods to reveal the dynamics of the process under study. These formal
      approaches differ from classical methods of investigating the dynamics of the
      process through numerical integration of ODEs because they additionally provide
      alternative representations which are amenable to discrete-state analysis and
      logical reasoning. Backed by these additional analysis methods, formal modeling
      approaches have been able to identify errors in published and widely-cited
      biological models. This paper provides an introduction to these analysis methods,
      and explains the benefits which they can bring to ensuring the consistency of
      biological models.

PMID- 22161347
TI  - Global parameter identification of stochastic reaction networks from single
      trajectories.
AB  - We consider the problem of inferring the unknown parameters of a stochastic
      biochemical network model from a single measured time-course of the concentration
      of some of the involved species. Such measurements are available, e.g., from live
      cell fluorescence microscopy in image-based systems biology. In addition,
      fluctuation time-courses from, e.g., fluorescence correlation spectroscopy (FCS)
      provide additional information about the system dynamics that can be used to more
      robustly infer parameters than when considering only mean concentrations.
      Estimating model parameters from a single experimental trajectory enables single
      cell measurements and quantification of cell-cell variability. We propose a novel
      combination of an adaptive Monte Carlo sampler, called Gaussian Adaptation (GaA),
      and efficient exact stochastic simulation algorithms (SSA) that allows parameter
      identification from single stochastic trajectories. We benchmark the proposed
      method on a linear and a non-linear reaction network at steady state and during
      transient phases. In addition, we demonstrate that the present method also
      provides an ellipsoidal volume estimate of the viable part of parameter space and
      is able to estimate the physical volume of the compartment in which the observed
      reactions take place.

PMID- 22161348
TI  - A systems biology view of adaptation in sensory mechanisms.
AB  - Adaptation, the desensitization to persistent changes in environmental
      conditions, is present throughout biological sensory mechanisms. Not
      surprisingly, it has been an active area of research to systems biologists. Here,
      we consider some of the models proposed to account for adaptation as well as the
      experiments used to motivate and validate these models. We discuss some salient
      features of these models including robustness, deadaptation, transient responses,
      and the response of these systems to more complex temporal stimuli. While most of
      these models have been used to study chemoattractant-induced responses in
      bacteria and amoebae, the system-theoretic issues associated with these systems
      are of importance in a broad spectrum of biological systems.

PMID- 22161350
TI  - Why and how to expand the role of systems biology in pharmaceutical research and
      development.
AB  - Seen from the perspective of funding organizations, investors, and the general
      public, the productivity of our world-wide biomedical research enterprise is
      declining despite increased investment. This opinion piece suggests a cause and a
      solution. The cause is the enormous complexity of human biology and
      pathophysiology. The unsolved human diseases involve so many interacting
      variables that single research laboratories headed by skilled principal
      investigators doing innovative experimental work cannot be expected to assemble
      the reductionist pieces into an integrated working model. Systems biology offers
      a solution, but it will require teamwork. Co-equal teams of experimental and
      computational biologists can construct multiscale differential equation models
      and test them against experimental data. A successful model provides actionable
      evidence-based guidance to the entire research and development team. These
      integrative biology teams may, for historical and cultural reasons, be
      unsustainable in academia, but they seem naturally suited to modern
      pharmaceutical research and development. One way to organize such teams and their
      workflow is described in detail.

PMID- 22161349
TI  - Leveraging modeling approaches: reaction networks and rules.
AB  - We have witnessed an explosive growth in research involving mathematical models
      and computer simulations of intracellular molecular interactions, ranging from
      metabolic pathways to signaling and gene regulatory networks. Many software tools
      have been developed to aid in the study of such biological systems, some of which
      have a wealth of features for model building and visualization, and powerful
      capabilities for simulation and data analysis. Novel high-resolution and/or high
      throughput experimental techniques have led to an abundance of qualitative and
      quantitative data related to the spatiotemporal distribution of molecules and
      complexes, their interactions kinetics, and functional modifications. Based on
      this information, computational biology researchers are attempting to build
      larger and more detailed models. However, this has proved to be a major
      challenge. Traditionally, modeling tools require the explicit specification of
      all molecular species and interactions in a model, which can quickly become a
      major limitation in the case of complex networks - the number of ways
      biomolecules can combine to form multimolecular complexes can be combinatorially
      large. Recently, a new breed of software tools has been created to address the
      problems faced when building models marked by combinatorial complexity. These
      have a different approach for model specification, using reaction rules and
      species patterns. Here we compare the traditional modeling approach with the new
      rule-based methods. We make a case for combining the capabilities of conventional
      simulation software with the unique features and flexibility of a rule-based
      approach in a single software platform for building models of molecular
      interaction networks.

PMID- 22161351
TI  - Multiscale mechanistic modeling in pharmaceutical research and development.
AB  - Discontinuation of drug development projects due to lack of efficacy or adverse
      events is one of the main cost drivers in pharmaceutical research and development
      (R&D). Investments have to be written-off and contribute to the total costs of a
      successful drug candidate receiving marketing authorization and allowing return
      on invest. A vital risk for pharmaceutical innovator companies is late stage
      clinical failure since costs for individual clinical trials may exceed the one
      billion Euro threshold. To guide investment decisions and to safeguard maximum
      medical benefit and safety for patients recruited in clinical trials, it is
      therefore essential to understand the clinical consequences of all information
      and data generated. The complexity of the physiological and pathophysiological
      processes and the sheer amount of information available overcharge the mental
      capacity of any human being and prevent a prediction of the success in clinical
      development. A rigorous integration of knowledge, assumption, and experimental
      data into computational models promises a significant improvement of the
      rationalization of decision making in pharmaceutical industry. We here give an
      overview of the current status of modeling and simulation in pharmaceutical R&D
      and outline the perspectives of more recent developments in mechanistic modeling.
      Specific modeling approaches for different biological scales ranging from
      intracellular processes to whole organism physiology are introduced and an
      example for integrative multiscale modeling of therapeutic efficiency in clinical
      oncology trials is showcased.

PMID- 22161352
TI  - Re-analysis of bipolar disorder and schizophrenia gene expression complements the
      Kraepelinian dichotomy.
AB  - The differential diagnosis of schizophrenia (SZ) and bipolar disorder (BD) is
      based solely on clinical features and upon a subset of overlapping symptoms.
      Within the last years, an increasing amount of clinical, epidemiological and
      genetic data suggested inconsistent with the Kraepelinian dichotomy. We performed
      re-analysis of genome-wide gene expression data obtained from postmortem
      prefrontal cortex (PEC) of both BD and SZ patients with matched controls from
      four independent microarray experiments. We found 2,577 and 477 genes
      specifically altered in BD and SZ, respectively. Of these, 164 genes were shared
      between the syndromes. We identified genes of the transcriptional and post
      transcriptional machineries altered in BD and genes of the development changed in
      SZ. Our results showed that the genomic expression profile of BD and SZ had some
      similarity but still could be well-distinguished by suitable statistical test.

PMID- 22161353
TI  - Bringing together models from bottom-up and top-down approaches: an application
      for growth of Escherichia coli on different carbohydrates.
AB  - Modeling in systems biology follows two lines: a data driven top-down approach
      that integrates experimental data from various "omics" technologies and a model
      based bottom-up approach where the model structure is given and kinetic
      parameters are chosen in such a way that an experimental observation can be
      reproduced quantitatively or qualitatively. Mathematical models are frequently
      used to elucidate cellular design principles in order to understand complex
      biochemical networks better. To show that both approaches lead to a consistent
      description of cellular dynamics, mathematical models from both approaches are
      explored. On the level of transcription factor activities a sufficient
      qualitative agreement is observed. Experimental data for the classical growth
      experiment of Escherichia coli on two carbon sources, glucose and lactose is
      available to set up the data driven model and to support the theoretical findings
      from the bottom-up approach.

PMID- 22161354
TI  - A differential equation model to investigate the dynamics of the bovine estrous
      cycle.
AB  - To investigate physiological factors affecting fertility of dairy cows, we
      developed a mechanistic mathematical model of the dynamics of the bovine estrous
      cycle. The model consists of 12 (delay) differential equations and 54 parameters.
      It simulates follicle and corpus luteum development and the periodic changes in
      hormones levels that regulate these processes. The model can be used to determine
      the level of control exerted by various system components on the functioning of
      the system. As an example, it was investigated which mechanisms could be
      candidates for regulation of the number of waves of follicle development per
      cycle. Important issues in model building and validation of our model were
      parameter identification, sensitivity analysis, stability, and prediction of
      model behavior in different scenarios.

PMID- 22161355
TI  - Reducing systems biology to practice in pharmaceutical company research; selected
      case studies.
AB  - Reviews of the productivity of the pharmaceutical industry have concluded that
      the current business model is unsustainable. Various remedies for this have been
      proposed, however, arguably these do not directly address the fundamental issue;
      namely, that it is the knowledge required to enable good decisions in the process
      of delivering a drug that is largely absent; in turn, this leads to a disconnect
      between our intuition of what the right drug target is and the reality of
      pharmacological intervention in a system such as a human disease state. As this
      system is highly complex, modelling will be required to elucidate emergent
      properties together with the data necessary to construct such models. Currently,
      however, both the models and data available are limited. The ultimate solution to
      the problem of pharmaceutical productivity may be the virtual human, however, it
      is likely to be many years, if at all, before this goal is realised. The current
      challenge is, therefore, whether systems modelling can contribute to improving
      productivity in the pharmaceutical industry in the interim and help to guide the
      optimal route to the virtual human. In this context, this chapter discusses the
      emergence of systems pharmacology in drug discovery from the interface of
      pharmacokinetic-pharmacodynamic modelling and systems biology. Examples of
      applications to the identification of optimal drug targets in given pathways,
      selecting drug modalities and defining biomarkers are discussed, together with
      future directions.

PMID- 22161356
TI  - System-scale network modeling of cancer using EPoC.
AB  - One of the central problems of cancer systems biology is to understand the
      complex molecular changes of cancerous cells and tissues, and use this
      understanding to support the development of new targeted therapies. EPoC
      (Endogenous Perturbation analysis of Cancer) is a network modeling technique for
      tumor molecular profiles. EPoC models are constructed from combined copy number
      aberration (CNA) and mRNA data and aim to (1) identify genes whose copy number
      aberrations significantly affect target mRNA expression and (2) generate markers
      for long- and short-term survival of cancer patients. Models are constructed by a
      combination of regression and bootstrapping methods. Prognostic scores are
      obtained from a singular value decomposition of the networks. We have previously
      analyzed the performance of EPoC using glioblastoma data from The Cancer Genome
      Atlas (TCGA) consortium, and have shown that resulting network models contain
      both known and candidate disease-relevant genes as network hubs, as well as
      uncover predictors of patient survival. Here, we give a practical guide how to
      perform EPoC modeling in practice using R, and present a set of alternative
      modeling frameworks.

PMID- 22161357
TI  - Early patient stratification and predictive biomarkers in drug discovery and
      development: a case study of ulcerative colitis anti-TNF therapy.
AB  - The current drug discovery paradigm is long, costly, and prone to failure. For
      projects in early development, lack of efficacy in Phase II is a major
      contributor to the overall failure rate. Efficacy failures often occur from one
      of two major reasons: either the investigational agent did not achieve the
      required pharmacology or the mechanism targeted by the investigational agent did
      not significantly contribute to the disease in the tested patient population. The
      latter scenario can arise due to insufficient study power stemming from patient
      heterogeneity. If the subset of disease patients driven by the mechanism that is
      likely to respond to the drug can be identified and selected before enrollment
      begins, efficacy and response rates should improve. This will not only augment
      drug approval percentages, but will also minimize the number of patients at risk
      of side effects in the face of a suboptimal response to treatment. Here we
      describe a systems biology approach using molecular profiling data from patients
      at baseline for the development of predictive biomarker content to identify
      potential responders to a molecular targeted therapy before the drug is tested in
      humans. A case study is presented where a classifier to predict response to a TNF
      targeted therapy for ulcerative colitis is developed a priori and verified
      against a test set of patients where clinical outcomes are known. This approach
      will promote the tandem development of drugs with predictive response, patient
      selection biomarkers.

PMID- 22161358
TI  - Biomedical atlases: systematics, informatics and analysis.
AB  - Biomedical imaging is ubiquitous in the Life Sciences. Technology advances, and
      the resulting multitude of imaging modalities, have led to a sharp rise in the
      quantity and quality of such images. In addition, computational models are
      increasingly used to study biological processes involving spatio-temporal changes
      from the cell to the organism level, e.g., the development of an embryo or the
      growth of a tumour, and models and images are extensively described in natural
      language, for example, in research publications and patient records. Together
      this leads to a major spatio-temporal data and model integration challenge.
      Biomedical atlases have emerged as a key technology in solving this integration
      problem. Such atlases typically include an image-based (2D and/or 3D) component
      as well as a conceptual representation (ontologies) of the organisms involved. In
      this chapter, we review the notion of atlases in the biomedical domain, how they
      can be created, how they provide an index to spatio-temporal experimental data,
      issues of atlas data integration and their use for the analysis of large volumes
      of biomedical data.

PMID- 22161359
TI  - International Clinical Trials Day & The Cochrane Library.

PMID- 22161360
TI  - WITHDRAWN: Caesarean delivery for the second twin.
AB  - BACKGROUND: The optimal mode of birth for a second twin in breech position is
      controversial, with support for both caesarean and vaginal birth. OBJECTIVES: The
      objective of this review was to assess the effects of caesarean birth compared
      with vaginal birth of a second twin not presenting cephalically. SEARCH METHODS:
      The Cochrane Pregnancy and Childbirth Group's Trials Register and bibliographies
      up to 31 January 2007. SELECTION CRITERIA: Randomised trials of caesarean birth
      compared with vaginal birth in women with a twin pregnancy where the second twin
      is not presenting cephalically. DATA COLLECTION AND ANALYSIS: All assessments of
      trial eligibility, quality and data extractions were done by the author without
      blinding. MAIN RESULTS: One trial involving 60 pairs of twins was included.
      Maternal febrile morbidity were increased in women allocated to the caesarean
      group (relative risk (RR) 3.67, 95% confidence interval (CI) 1.15-11.69), and
      there was a trend to an increased need for use of general anaesthesia (RR 2.40,
      95% CI 0.98-5.88). No differences were detected in neonatal outcome. AUTHORS'
      CONCLUSIONS: Caesarean section for the birth of a second twin not presenting
      cephalically is associated with increased maternal febrile morbidity with, as
      yet, no identified improvement in neonatal outcome. This policy should not be
      adopted except within the context of further controlled trials.

PMID- 22161361
TI  - Pre-operative traction for hip fractures in adults.
AB  - BACKGROUND: Following a hip fracture, traction may be applied to the injured limb
      before surgery. This is an update of a Cochrane review first published in 1997,
      and previously updated in 2006. OBJECTIVES: To evaluate the effects of traction
      applied to the injured limb prior to surgery for a fractured hip. Different
      methods of applying traction (skin or skeletal) were considered. SEARCH METHODS:
      We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register
      (April 2011), the Cochrane Central Register of Controlled Trials (in The Cochrane
      Library 2011, Issue 4), MEDLINE (1948 to April week 2 2011), EMBASE (1980 to 2011
      week 16), and CINAHL (1982 to 1 April 2011), conference proceedings, trials
      registries and reference lists of articles. SELECTION CRITERIA: All randomised or
      quasi-randomised trials comparing either skin or skeletal traction with no
      traction, or skin with skeletal traction for patients with an acute hip fracture
      prior to surgery. DATA COLLECTION AND ANALYSIS: At least two authors
      independently assessed trial quality and extracted data. Additional information
      was sought from all trialists. Wherever appropriate and possible, data were
      pooled. MAIN RESULTS: One new trial was included in this update. In all, 11
      trials (six were randomised and five were quasi-randomised), involving a total of
      1654 predominantly elderly patients with hip fractures, are included in the
      review. Most trials were at risk of bias, particularly that resulting from
      inadequate allocation concealment, lack of assessor blinding and incomplete
      outcome assessment. Only very limited data pooling was possible.Ten trials
      compared predominantly skin traction with no traction. The available data
      provided no evidence of benefit from traction either in the relief of pain (pain
      soon after immobilisation (visual analogue score 0: none to 10: worst pain): mean
      difference 0.11, 95% CI -0.27 to 0.50; 3 trials), ease of fracture reduction or
      quality of fracture reduction at time of surgery. There were inconclusive data
      for pressures sores and other complications, including fracture fixation failure.
      Three minor adverse effects (sensory disturbance and skin blisters) related to
      skin traction were reported.One of the above trials included both skin and
      skeletal traction groups. This trial and one other compared skeletal traction
      with skin traction and found no important differences between these two methods,
      although the initial application of skeletal traction was noted as being more
      painful and more costly. AUTHORS' CONCLUSIONS: From the evidence available, the
      routine use of traction (either skin or skeletal) prior to surgery for a hip
      fracture does not appear to have any benefit. However, the evidence is also
      insufficient to rule out the potential advantages for traction, in particular for
      specific fracture types, or to confirm additional complications due to traction
      use.Given the increasing lack of evidence for the use of pre-operative traction,
      the onus should now be on clinicians who persist in using pre-operative traction
      to either stop using it or to use it only in the context of a well-designed
      randomised controlled trial.

PMID- 22161362
TI  - Epidural versus non-epidural or no analgesia in labour.
AB  - BACKGROUND: Epidural analgesia is a central nerve block technique achieved by
      injection of a local anaesthetic close to the nerves that transmit pain and is
      widely used as a form of pain relief in labour. However, there are concerns
      regarding unintended adverse effects on the mother and infant. OBJECTIVES: To
      assess the effects of all modalities of epidural analgesia (including combined
      spinal-epidural) on the mother and the baby, when compared with non-epidural or
      no pain relief during labour. SEARCH METHODS: We searched the Cochrane Pregnancy
      and Childbirth Group's Trials Register (31 March 2011). SELECTION CRITERIA:
      Randomised controlled trials comparing all modalities of epidural with any form
      of pain relief not involving regional blockade, or no pain relief in labour. DATA
      COLLECTION AND ANALYSIS: Two of the review authors independently assessed trials
      for eligibility, methodological quality and extracted all data. We entered data
      into RevMan and double checked it for accuracy. Primary analysis was by intention
      to treat; we conducted subgroup and sensitivity analyses where substantial
      heterogeneity was evident. MAIN RESULTS: We included 38 studies involving 9658
      women; all but five studies compared epidural analgesia with opiates. Epidural
      analgesia was found to offer better pain relief (mean difference (MD) -3.36, 95%
      confidence interval (CI) -5.41 to -1.31, three trials, 1166 women); a reduction
      in the need for additional pain relief (risk ratio (RR) 0.05, 95% CI 0.02 to
      0.17, 15 trials, 6019 women); a reduced risk of acidosis (RR 0.80, 95% CI 0.68 to
      0.94, seven trials, 3643 women); and a reduced risk of naloxone administration
      (RR 0.15, 95% CI 0.10 to 0.23, 10 trials, 2645 women). However, epidural
      analgesia was associated with an increased risk of assisted vaginal birth (RR
      1.42, 95% CI 1.28 to 1.57, 23 trials, 7935 women), maternal hypotension (RR
      18.23, 95% CI 5.09 to 65.35, eight trials, 2789 women), motor-blockade (RR 31.67,
      95% CI 4.33 to 231.51, three trials, 322 women), maternal fever (RR 3.34, 95% CI
      2.63 to 4.23, six trials, 2741 women), urinary retention (RR 17.05, 95% CI 4.82
      to 60.39, three trials, 283 women), longer second stage of labour (MD 13.66
      minutes, 95% CI 6.67 to 20.66, 13 trials, 4233 women), oxytocin administration
      (RR 1.19, 95% CI 1.03 to 1.39, 13 trials, 5815 women) and an increased risk of
      caesarean section for fetal distress (RR 1.43, 95% CI 1.03 to 1.97, 11 trials,
      4816 women). There was no evidence of a significant difference in the risk of
      caesarean section overall (RR 1.10, 95% CI 0.97 to 1.25, 27 trials, 8417 women),
      long-term backache (RR 0.96, 95% CI 0.86 to 1.07, three trials, 1806 women),
      Apgar score less than seven at five minutes (RR 0.80, 95% CI 0.54 to 1.20, 18
      trials, 6898 women), and maternal satisfaction with pain relief (RR 1.31, 95% CI
      0.84 to 2.05, seven trials, 2929 women). We found substantial heterogeneity for
      the following outcomes: pain relief; maternal satisfaction; need for additional
      means of pain relief; length of second stage of labour; and oxytocin
      augmentation. This could not be explained by subgroup or sensitivity analyses,
      where data allowed analysis. No studies reported on rare but potentially serious
      adverse effects of epidural analgesia. AUTHORS' CONCLUSIONS: Epidural analgesia
      appears to be effective in reducing pain during labour. However, women who use
      this form of pain relief are at increased risk of having an instrumental
      delivery. Epidural analgesia had no statistically significant impact on the risk
      of caesarean section, maternal satisfaction with pain relief and long-term
      backache and did not appear to have an immediate effect on neonatal status as
      determined by Apgar scores. Further research may be helpful to evaluate rare but
      potentially severe adverse effects of epidural analgesia on women in labour and
      long-term neonatal outcomes.

PMID- 22161363
TI  - Long-chain polyunsaturated fatty acid supplementation in infants born at term.
AB  - BACKGROUND: The n-3 and n-6 fatty acids linolenic acid and linoleic acid are
      precursors of the n-3 and n-6 long chain fatty acids (LCPUFA). Infant formula has
      historically only contained the precursor fatty acids. Over the last few years,
      some manufacturers have added LCPUFA to formulae and marketed them as providing
      an advantage for the development of term infants. OBJECTIVES: To assess whether
      supplementation of formula with LCPUFA is safe and of benefit to term infants.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (The Cochrane Library, April, 2011), MEDLINE (1966 to April 2011), EMBASE (1980
      to April 2011), CINAHL (December 1982 to April 2011) and abstracts of the Society
      for Pediatric Research (1980 to 2010). No language restrictions were applied.
      SELECTION CRITERIA: Randomised and quasi randomised trials comparing LCPUFA
      supplemented vs. non-supplemented formula milk and with clinical endpoints were
      reviewed. DATA COLLECTION AND ANALYSIS: Methodological quality of studies was
      assessed using the guidelines of Cochrane neonatal review group. Data were sought
      regarding effects on visual acuity, neurodevelopmental outcomes and physical
      growth. When appropriate, meta-analysis was conducted to provide a pooled
      estimate of effect. MAIN RESULTS: Twenty-five randomised studies were identified;
      fifteen were included (n = 1889) and ten excluded.Visual acuity was assessed by
      nine studies. Visual evoked potential was used in six studies, two used Teller
      cards and one used both. Four studies reported beneficial effects while the
      remaining five did not.Neurodevelopmental outcome was measured by eleven studies.
      Bayley scales of infant development (BSID) was used in nine studies; only two
      showed beneficial effects. Meta-analysis did not show significant benefits of
      supplementation. One study followed the infants up to nine years of age and did
      not find benefit of supplementation. One study reported better novelty preference
      measured by Fagan Infant test at nine months. Another study reported better
      problem solving at 10 months. One study used Brunet and Lezine test to assess the
      developmental quotient and did not find beneficial effects.Physical growth was
      measured by thirteen studies; none found beneficial or harmful effects of
      supplementation. Meta-analysis found that supplemented group may have marginally
      lower weight at one year of age. AUTHORS' CONCLUSIONS: Majority of the RCTS have
      not shown beneficial effects of LCPUFA supplementation on the neurodevelopmental
      outcomes of term infants. The beneficial effects on visual acuity have not been
      consistently demonstrated. Routine supplementation of term infant milk formula
      with LCPUFA can not be recommended.

PMID- 22161364
TI  - Duration of treatment for asymptomatic bacteriuria during pregnancy.
AB  - BACKGROUND: A Cochrane systematic review has shown that drug treatment of
      asymptomatic bacteriuria in pregnant women substantially decreases the risk of
      pyelonephritis and reduces the risk of preterm delivery. However, it is not clear
      whether single-dose therapy is as effective as longer conventional antibiotic
      treatment. OBJECTIVES: To assess the effects of different durations of treatment
      for asymptomatic bacteriuria in pregnancy. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2011) and
      reference lists of identified articles. SELECTION CRITERIA: Randomized and quasi
      randomized trials comparing antimicrobial therapeutic regimens that differed in
      duration (particularly comparing single dose with longer duration regimens) in
      pregnant women diagnosed with asymptomatic bacteriuria. DATA COLLECTION AND
      ANALYSIS: We assessed trial quality and extracted data independently. MAIN
      RESULTS: We included 13 studies, involving 1622 women. All were comparisons of
      single-dose treatment with four- to seven-day treatments. The trials were
      generally of limited quality. The 'no cure rate' for asymptomatic bacteriuria in
      pregnant women was slightly higher for the single-dose than for the short-course
      treatment; however, these results were not statistically significant and showed
      heterogeneity. When comparing the trials that used the same antibiotic in both
      treatment and control groups with the trials that used different antibiotics in
      both groups, the 'no cure rate' risk ratio was similar. There was no
      statistically significant difference in the recurrence of asymptomatic
      bacteriuria rate between treatment and control groups. Slight differences were
      detected for preterm births and pyelonephritis although, apart from one trial,
      the sample size of the trials was inadequate. Single-dose treatment was
      associated with a decrease in reports of 'any side-effects' . AUTHORS'
      CONCLUSIONS: Single-dose regimen of antibiotics may be less effective than the
      seven-day regimen. Women with asymptomatic bacteriuria in pregnancy should be
      treated by the standard regimen of antibiotics until more data become available
      testing seven-day compared with three- or five-day regimens.

PMID- 22161365
TI  - Amnioinfusion for preterm premature rupture of membranes.
AB  - BACKGROUND: Preterm premature rupture of membranes (PPROM) is a leading cause of
      perinatal morbidity and mortality. Amnioinfusion aims to restore amniotic fluid
      volume by infusing a solution into the uterine cavity. OBJECTIVES: The objective
      of this review was to assess the effects of amnioinfusion for PPROM on perinatal
      and maternal morbidity and mortality. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (30 September 2011). SELECTION
      CRITERIA: Randomised trials of amnioinfusion compared to no amnioinfusion in
      women with PPROM. DATA COLLECTION AND ANALYSIS: Three review authors
      independently assessed trials for inclusion. Two review authors independently
      assessed trial quality and extracted data. Data were checked for accuracy. MAIN
      RESULTS: We included five trials but we only analysed data from four studies
      (with a total of 241 participants). One trial did not contribute any data to the
      review.Transcervical amnioinfusion improved fetal umbilical artery pH at delivery
      (mean difference 0.11; 95% confidence interval (CI) 0.08 to 0.14; one trial, 61
      participants) and reduced persistent variable decelerations during labour (risk
      ratio (RR) 0.52; 95% CI 0.30 to 0.91; one trial, 86 participants).Transabdominal
      amnioinfusion was associated with a reduction in neonatal death (RR 0.30; 95% CI
      0.14 to 0.66; two trials, 94 participants), neonatal sepsis (RR 0.26, 95% CI 0.11
      to 0.61; one trial, 60 participants), pulmonary hypoplasia (RR 0.22; 95% CI 0.06
      to 0.88; one trial, 34 participants) and puerperal sepsis (RR 0.20; 95% CI 0.05
      to 0.84; one trial, 60 participants). Women in the amnioinfusion group were also
      less likely to deliver within seven days of membrane rupture (RR 0.18; 95% CI
      0.05 to 0.70; one trial, 34 participants). These results should be treated with
      circumspection as the positive findings were mainly due to one trial with unclear
      allocation concealment. AUTHORS' CONCLUSIONS: These results are encouraging but
      are limited by the sparse data and unclear methodological robustness, therefore
      further evidence is required before amnioinfusion for PPROM can be recommended
      for routine clinical practice.

PMID- 22161366
TI  - Diuretics for respiratory distress syndrome in preterm infants.
AB  - BACKGROUND: Lung edema may complicate respiratory distress syndrome (RDS) in
      preterm infants. OBJECTIVES: The aim of this review was to assess the risks and
      benefits of diuretic administration in preterm infants with RDS. SEARCH METHODS:
      The standard search method of the Cochrane Neonatal Review Group was used. The
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library),
      MEDLINE and EMBASE were searched. These searches were updated in April 2003,
      March 2007, January 2011. In addition, the abstract books of the American
      Thoracic Society and Society for Pediatric Research were searched. MEDLINE and
      CENTRAL search was conducted using the keyword "Respiratory Distress Syndrome"
      alone, to find studies of medications recently classified as diuretics, such as
      theophylline. In addition, EMBASE, controlled-trials.com and clinicaltrials.gov
      searches were completed in January 2011. MEDLINE search updated to August 2011.
      SELECTION CRITERIA: Trials were included in which preterm infants with RDS and
      less than five days of age were randomly allocated to diuretic administration. Of
      those trials, studies were only included in which at least one of the following
      outcomes measures was evaluated: mortality, patent ductus arteriosus, hypovolemic
      shock, intraventricular hemorrhage, renal failure, duration of oxygen
      supplementation, duration of mechanical ventilation, need for oxygen
      supplementation at 28 days of life, oxygen supplementation at 36 weeks of
      postmenstrual age (gestational age + postnatal age), length of stay, number of
      rehospitalizations during the first year of life, and neurodevelopmental outcome.
      DATA COLLECTION AND ANALYSIS: The standard method for the Cochrane Collaboration,
      which is described in the Cochrane Collaboration Handbook, was used. Two
      investigators extracted, assessed and coded separately all data for each study.
      Any disagreement was resolved by discussion. MAIN RESULTS: Seven studies met
      inclusion criteria. Six studies using furosemide were done before the current era
      of prenatal steroids, surfactant and fluid restriction. Furosemide administration
      had no long-term benefits. Furosemide-induced transient improvement in pulmonary
      function did not outweigh an increased risk for patent ductus arteriosus and for
      hemodynamic instability. In one recent study, theophylline had no long-term
      benefits. Theophylline significantly decreased the risk of oligoanuria and
      transiently increased renal function, but did not significantly affect renal
      function at discharge or other outcomes. AUTHORS' CONCLUSIONS: There are no data
      to support routine administration of furosemide in preterm infants with RDS.
      Elective administration of furosemide to any patient with RDS should be carefully
      weighed against the risk of precipitating hypovolemia or developing a symptomatic
      patent ductus arteriosus. There are not enough data to support routine
      administration of low-dose theophylline in preterm infants with RDS.

PMID- 22161367
TI  - Interventions for preventing obesity in children.
AB  - BACKGROUND: Prevention of childhood obesity is an international public health
      priority given the significant impact of obesity on acute and chronic diseases,
      general health, development and well-being. The international evidence base for
      strategies that governments, communities and families can implement to prevent
      obesity, and promote health, has been accumulating but remains unclear.
      OBJECTIVES: This review primarily aims to update the previous Cochrane review of
      childhood obesity prevention research and determine the effectiveness of
      evaluated interventions intended to prevent obesity in children, assessed by
      change in Body Mass Index (BMI). Secondary aims were to examine the
      characteristics of the programs and strategies to answer the questions "What
      works for whom, why and for what cost?" SEARCH METHODS: The searches were re-run
      in CENTRAL, MEDLINE, EMBASE, PsychINFO and CINAHL in March 2010 and searched
      relevant websites. Non-English language papers were included and experts were
      contacted. SELECTION CRITERIA: The review includes data from childhood obesity
      prevention studies that used a controlled study design (with or without
      randomisation). Studies were included if they evaluated interventions, policies
      or programs in place for twelve weeks or more. If studies were randomised at a
      cluster level, 6 clusters were required. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data and assessed the risk of bias of included
      studies.  Data was extracted on intervention implementation, cost, equity and
      outcomes. Outcome measures were grouped according to whether they measured
      adiposity, physical activity (PA)-related behaviours or diet-related behaviours. 
      Adverse outcomes were recorded. A meta-analysis was conducted using available BMI
      or standardised BMI (zBMI) score data with subgroup analysis by age group (0-5, 6
      12, 13-18 years, corresponding to stages of developmental and childhood
      settings). MAIN RESULTS: This review includes 55 studies (an additional 36
      studies found for this update). The majority of studies targeted children aged 6
      12 years.  The meta-analysis included 37 studies of 27,946 children and
      demonstrated that programmes were effective at reducing adiposity, although not
      all individual interventions were effective, and there was a high level of
      observed heterogeneity (I(2)=82%).  Overall, children in the intervention group
      had a standardised mean difference in adiposity (measured as BMI or zBMI) of 
      0.15kg/m(2) (95% confidence interval (CI): -0.21 to -0.09).  Intervention effects
      by age subgroups were -0.26kg/m(2) (95% CI:-0.53 to 0.00) (0-5 years), 
      0.15kg/m(2) (95% CI -0.23 to -0.08) (6-12 years), and -0.09kg/m(2) (95% CI -0.20
      to 0.03) (13-18 years). Heterogeneity was apparent in all three age groups and
      could not explained by randomisation status or the type, duration or setting of
      the intervention.  Only eight studies reported on adverse effects and no evidence
      of adverse outcomes such as unhealthy dieting practices, increased prevalence of
      underweight or body image sensitivities was found.  Interventions did not appear
      to increase health inequalities although this was examined in fewer studies.
      AUTHORS' CONCLUSIONS: We found strong evidence to support beneficial effects of
      child obesity prevention programmes on BMI, particularly for programmes targeted
      to children aged six to 12 years. However, given the unexplained heterogeneity
      and the likelihood of small study bias, these findings must be interpreted
      cautiously. A broad range of programme components were used in these studies and
      whilst it is not possible to distinguish which of these components contributed
      most to the beneficial effects observed, our synthesis indicates the following to
      be promising policies and strategies:. school curriculum that includes healthy
      eating, physical activity and body image. increased sessions for physical
      activity and the development of fundamental movement skills throughout the school
      week. improvements in nutritional quality of the food supply in schools.
      environments and cultural practices that support children eating healthier foods
      and being active throughout each day. support for teachers and other staff to
      implement health promotion strategies and activities (e.g. professional
      development, capacity building activities). parent support and home activities
      that encourage children to be more active, eat more nutritious foods and spend
      less time in screen based activitiesHowever, study and evaluation designs need to
      be strengthened, and reporting extended to capture process and implementation
      factors, outcomes in relation to measures of equity, longer term outcomes,
      potential harms and costs.Childhood obesity prevention research must now move
      towards identifying how effective intervention components can be embedded within
      health, education and care systems and achieve long term sustainable impacts.  

PMID- 22161368
TI  - Macrolide antibiotics for cystic fibrosis.
AB  - BACKGROUND: Macrolide antibiotics may have a modifying role in diseases which
      involve airway infection and inflammation, like cystic fibrosis. OBJECTIVES: To
      test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics:
      1. improve clinical status compared to placebo or another antibiotic; 2. do not
      have unacceptable adverse effects. If benefit was demonstrated, we aimed to
      assess the optimal type, dose and duration of macrolide therapy. SEARCH METHODS:
      We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials
      Register comprising references identified from comprehensive electronic database
      searches, handsearching relevant journals and abstract books of conference
      proceedings.We contacted investigators known to work in the field, previous
      authors and pharmaceutical companies manufacturing macrolide antibiotics for
      unpublished or follow-up data (May 2010).Latest search of the Group's Cystic
      Fibrosis Trials Register: 09 February 2011. SELECTION CRITERIA: Randomised
      controlled trials of macrolide antibiotics compared to: placebo; another class of
      antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a
      different dose. DATA COLLECTION AND ANALYSIS: Two authors independently extracted
      data and assessed risk of bias. Seven groups were contacted and provided
      additional data which were incorporated into the review. MAIN RESULTS: Ten of 31
      studies identified were included (959 patients). Five studies with a low risk of
      bias examined azithromycin versus placebo and demonstrated consistent improvement
      in forced expiratory volume in one second over six months (mean difference at six
      months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four
      studies)). Patients treated with azithromycin were approximately twice as likely
      to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95%
      confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was
      a significant reduction in need for oral antibiotics and greater weight gain in
      those taking azithromycin. Adverse events were uncommon and not obviously
      associated with azithromycin, although a once-weekly high dose regimen was
      associated with more frequent gastrointestinal adverse events. Treatment with
      azithromycin was associated with reduced identification of Staphylococcus aureus
      on respiratory culture, but also a significant increase in macrolide resistance.
      AUTHORS' CONCLUSIONS: This review provides evidence of improved respiratory
      function after six months of azithromycin. Data beyond six months were less
      clear, although reduction in pulmonary exacerbation was sustained. Treatment
      appeared safe over a six-month period; however, emergence of macrolide resistance
      was a concern. A multi-centre trial examining long-term effects of this
      antibiotic treatment is needed, especially for infants recognised through newborn
      screening.

PMID- 22161369
TI  - Interventions for involutional lower lid entropion.
AB  - BACKGROUND: Entropion is a condition in which the eyelid margin turns in against
      the eyeball. Involutional or senile entropion is one of the most common lower lid
      malpositions in the elderly. The interventions described and currently used for
      the treatment of this condition are surgical in nature, although non-surgical
      temporary medical treatment for the early stages of entropion has also been
      reported. The relative effectiveness of these interventions has not yet been
      resolved. OBJECTIVES: To examine the effect of interventions for involutional
      entropion and to assess whether any method is superior to any other. SEARCH
      METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group
      Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to
      November 2011), EMBASE (January 1980 to November 2011), the metaRegister of
      Controlled Trials (mRCT) (www.controlled-trials.com),ClinicalTrials.gov
      (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry
      Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language
      restrictions in the electronic searches for trials. The electronic databases were
      last searched on 2 November 2011. We also searched oculoplastic textbooks,
      conference proceedings from the European and American Society of Ophthalmic
      Plastic and Reconstructive Surgery (ESOPRS, ASOPRS), European Ophthalmological
      Society (SOE), the Association for Recearch in Vision and Ophthalmology (ARVO)
      and American Academy of Ophthalmology (AAO) for the years 2000 to 2009 to
      identify relevant data. We attempted to contact researchers who are active in
      this field for information about further published or unpublished studies.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) with no
      restriction on date or language comparing two or more surgical methods for
      correction of involutional lower eyelid entropion in people older than 60 years
      of age with involutional lower lid entropion. DATA COLLECTION AND ANALYSIS: Each
      review author independently assessed study abstracts identified from the
      electronic and manual searches. Author analysis was then compared and full papers
      for appropriate studies were obtained according to the inclusion criteria.
      Disagreements between the authors were resolved by discussion. MAIN RESULTS: We
      identified one RCT which met our inclusion criteria and was included in this
      review. Sixty-three participants with primary involutional lower eyelid entropion
      were randomised to everting sutures alone or everting sutures with a lateral
      tarsal strip. Eight participants were lost to follow-up. The trial indicates that
      the combined procedure for horizontal and vertical eyelid tightening in the form
      of everting sutures and lateral tarsal strip is highly curative for involutional
      entropion compared to vertical tightening in the form of everting sutures alone.
      The superiority of the combined approach is also supported by many good quality
      uncontrolled studies on specific surgical procedures but these were not included
      in the analysis as they were not part of the inclusion criteria. AUTHORS'
      CONCLUSIONS: A single RCT showed that the combination of horizontal and vertical
      eyelid tightening with everting sutures and lateral tarsal strip is highly
      efficient for entropion compared to vertical tightening with everting sutures
      alone. Retrospective case series studies also support the combined surgical
      repair but details from these studies on specific surgical techniques cannot be
      included in the analysis.Evidence from a single RCT is unlikely to change
      clinical practice and thus it is still our view that there is a clear need for
      more randomised studies comparing two or more surgical techniques for entropion
      surgery addressing the recurrence and complications rate.

PMID- 22161370
TI  - Behavioural and cognitive interventions with or without other treatments for the
      management of faecal incontinence in children.
AB  - BACKGROUND: Faecal incontinence is a common and potentially distressing disorder
      of childhood. OBJECTIVES: To assess the effects of behavioural and/or cognitive
      interventions for the management of faecal incontinence in children. SEARCH
      METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register
      (searched 28 October 2011), which contains trials identified from the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE and CINAHL, and
      handsearching of journals and conference proceedings, and the reference lists of
      relevant articles. We contacted authors in the field to identify any additional
      or unpublished studies. SELECTION CRITERIA: Randomised and quasi-randomised
      trials of behavioural and/or cognitive interventions with or without other
      treatments for the management of faecal incontinence in children. DATA COLLECTION
      AND ANALYSIS: Reviewers selected studies from the literature, assessed study
      quality, and extracted data. Data were combined in a meta-analysis when
      appropriate. MAIN RESULTS: Twenty one randomised trials with a total of 1371
      children met the inclusion criteria. Sample sizes were generally small. All
      studies but one investigated children with functional faecal incontinence.
      Interventions varied amongst trials and few outcomes were shared by trials
      addressing the same comparisons.Combined results of nine trials showed higher
      rather than lower rates of persisting symptoms of faecal incontinence up to 12
      months when biofeedback was added to conventional treatment (OR 1.11 CI 95% 0.78
      to 1.58). This result was consistent with that of two trials with longer follow
      up (OR 1.31 CI 95% 0.80 to 2.15). In one trial the adjunct of anorectal manometry
      to conventional treatment did not result in higher success rates in chronically
      constipated children (OR 1.40 95% CI 0.72 to 2.73 at 24 months).In one small
      trial the adjunct of behaviour modification to laxative therapy was associated
      with a significant reduction in children's soiling episodes at both the three
      month (OR 0.14 CI 95% 0.04 to 0.51) and the 12 month assessment (OR 0.20 CI 95%
      0.06 to 0.65). AUTHORS' CONCLUSIONS: There is no evidence that biofeedback
      training adds any benefit to conventional treatment in the management of
      functional faecal incontinence in children. There was not enough evidence on
      which to assess the effects of biofeedback for the management of organic faecal
      incontinence. There is some evidence that behavioural interventions plus laxative
      therapy, rather than laxative therapy alone, improves continence in children with
      functional faecal incontinence associated with constipation.

PMID- 22161371
TI  - Antidepressants for cocaine dependence and problematic cocaine use.
AB  - BACKGROUND: Cocaine dependence is a disorder for which no pharmacological
      treatment of proven efficacy exists, advances in the neurobiology could guide
      future medication development. OBJECTIVES: To investigate the efficacy and
      acceptability of antidepressants alone or in combination with any psychosocial
      intervention for the treatment of cocaine dependence and problematic cocaine use.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), PubMed, EMBASE and CINAHL in July 2011 and researchers for unpublished
      trials. SELECTION CRITERIA: Randomised clinical trials comparing antidepressants
      alone or associated with psychosocial intervention with placebo, no treatment,
      other pharmacological or psychosocial interventions. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trial quality and extracted data.
      MAIN RESULTS: 37 studies were included in the review (3551
      participants).Antidepressants versus placebo: results for dropouts did not show
      evidence of difference, 31 studies, 2819 participants, RR 1.03 (Cl 95% 0.93 to
      1.14). Looking at Abstinence from cocaine use, even though not statistically
      significant, the difference shown by the analysis in the three-weeks abstinence
      rate was in favour of antidepressants (eight studies, 942 participants, RR 1.22
      (Cl 95% 0.99 to 1.51)). Considering only studies involving tricyclics, five
      studies, 367 participants, or only desipramine, four studies, 254 participants,
      the evidence was in favour of antidepressants. However, selecting only studies
      with operationally defined diagnostic criteria, statistical significance
      favouring antidepressants, as well as the trend for significance shown by the
      full sample, disappeared. Looking at safety issues, the results did not show
      evidence of differences (number of patients withdrawn for medical reasons,
      thirteen studies, 1396 participants, RR 1.39 (Cl 95% 0.91 to 2.12)). Subgroup
      analysis considering length of the trial, associated opioid dependence or
      associated psychosocial interventions as confounding factors, failed in showing
      consistent and statistically significant differences in favour of
      antidepressants.Antidepressants versus other drugs: Comparing antidepressants
      with dopamine agonists or with anticonvulsants, no evidence of differences was
      shown on dropouts and on other outcomes (abstinence from cocaine use, adverse
      events). AUTHORS' CONCLUSIONS: At the current stage of evidence data do not
      support the efficacy of antidepressants in the treatment of cocaine
      abuse/dependence. Partially positive results obtained on secondary outcome
      measures, such as depression severity, do not seem to be associated with an
      effect on direct indicators of cocaine abuse/dependence. Antidepressants cannot
      be considered a mainstay of treatment for unselected cocaine abusers/dependents.

PMID- 22161372
TI  - Naftidrofuryl for dementia.
AB  - BACKGROUND: Dementia is a brain disorder characterized by the permanent loss of
      higher cognitive functions. A number of vasodilatory drug treatments are
      prescribed for dementia. Naftidrofuryl is one such medicine which is reported to
      improve clinical symptoms significantly. The efficacy and possible adverse events
      of naftidrofuryl need to be reviewed systematically and assessed critically to
      inform clinical practice and guide the continued search for new treatment
      regimens. OBJECTIVES: To evaluate the efficacy and safety of naftidrofuryl in the
      treatment of dementia. SEARCH METHODS: We searched ALOIS: the Cochrane Dementia
      and Cognitive Improvement Group's Specialized Register on 11 January 2011 using
      the terms: naftidrofuryl. ALOIS contains records of clinical trials from major
      healthcare databases (MEDLINE, EMBASE, PsycINFO, LILACS and CINAHL), trial
      registries (such as ClinicalTrials.gov) and grey literature sources. SELECTION
      CRITERIA: Randomised placebo-controlled trials in which patients with dementia
      were treated with naftidrofuryl were considered eligible for inclusion. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected trials for
      inclusion, assessed trial quality, and extracted data using data extraction
      forms. The domains assessed for risk of bias were sequence generation, allocation
      concealment, blinding, incomplete outcome data, and selective outcome reporting.
      We used odds ratios (OR) for reporting dichotomous data, and mean differences
      (MD) and standardized mean differences (SMD) for continuous data. We assessed
      statistical heterogeneity using the I(2) statistic. MAIN RESULTS: We identified
      nine randomised controlled trials involving 847 patients with Alzheimer's
      disease, vascular dementia, mixed dementia, senile dementia and unspecified
      dementia. The beneficial effects were found on functional performance and
      behaviour (-1.04 standardized points, 95% CI -1.73 to -0.35, P = 0.003) with a
      high-level heterogeneity (I(2) = 54%), and mood (-0.80 standardized points, 95%
      CI -1.26 to -0.34, P=0.0006) for patients with dementia, as well as on cognitive
      function (-0.36 standardized points, 95% CI -0.71 to -0.02, P=0.04). However,
      this was not confirmed by clinical global measures. Naftidrofuryl was found to be
      well-tolerated by patients with dementia. AUTHORS' CONCLUSIONS: Oral
      administration of naftidrofuryl is well-tolerated by patients with dementia.The
      low-quality evidence shows that, by use of naftidrofuryl, people with dementia
      may benefit on performance, behaviour, cognition, and mood. However, the benefit
      on global impression is inconsistent and unconvincing.

PMID- 22161373
TI  - Parent training interventions for Attention Deficit Hyperactivity Disorder (ADHD)
      in children aged 5 to 18 years.
AB  - BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a
      neurodevelopmental disorder characterised by high levels of inattention,
      hyperactivity and impulsivity that are present before the age of seven years,
      seen in a range of situations, inconsistent with the child's developmental level
      and causing social or academic impairment. Parent training programmes are
      psychosocial interventions aimed at training parents in techniques to enable them
      to manage their children's challenging behaviour. OBJECTIVES: To determine
      whether parent training interventions are effective in reducing ADHD symptoms and
      associated problems in children aged between five and eigtheen years with a
      diagnosis of ADHD, compared to controls with no parent training intervention.
      SEARCH METHODS: We searched the following electronic databases (for all available
      years until September 2010): CENTRAL (2010, Issue 3), MEDLINE (1950 to 10
      September 2010), EMBASE (1980 to 2010 Week 36), CINAHL (1937 to 13 September
      2010), PsycINFO (1806 to September Week 1 2010), Dissertation Abstracts
      International (14 September 2010) and the metaRegister of Controlled Trials (14
      September 2010). We contacted experts in the field to ask for details of
      unpublished or ongoing research. SELECTION CRITERIA: Randomised (including quasi
      randomised) studies comparing parent training with no treatment, a waiting list
      or treatment as usual (adjunctive or otherwise). We included studies if ADHD was
      the main focus of the trial and participants were over five years old and had a
      clinical diagnosis of ADHD or hyperkinetic disorder that was made by a specialist
      using the operationalised diagnostic criteria of the DSM-III/DSM-IV or ICD-10. We
      only included trials that reported at least one child outcome. DATA COLLECTION
      AND ANALYSIS: Four authors were involved in screening abstracts and at least 2
      authors looked independently at each one. We reviewed a total of 12,691 studies
      and assessed five as eligible for inclusion. We extracted data and assessed the
      risk of bias in the five included trials. Opportunities for meta-analysis were
      limited and most data that we have reported are based on single studies. MAIN
      RESULTS: We found five studies including 284 participants that met the inclusion
      criteria, all of which compared parent training with de facto treatment as usual
      (TAU). One study included a nondirective parent support group as a second control
      arm.  Four studies targeted children's behaviour problems and one assessed
      changes in parenting skills. Of the four studies targeting children's behaviour,
      two focused on behaviour at home and two focused on behaviour at school. The two
      studies focusing on behaviour at home had different findings: one found no
      difference between parent training and treatment as usual, whilst the other
      reported statistically significant results for parent training versus control.
      The two studies of behaviour at school also had different findings: one study
      found no difference between groups, whilst the other reported positive results
      for parent training when ADHD was not comorbid with oppositional defiant
      disorder. In this latter study, outcomes were better for girls and for children
      on medication.We assessed the risk of bias in most of the studies as unclear at
      best and often as high. Information on randomisation and allocation concealment
      did not appear in any study report. Inevitably, blinding of participants or
      personnel was impossible for this intervention; likewise, blinding of outcome
      assessors (who were most often the parents who had delivered the intervention)
      was impossible.We were only able to conduct meta-analysis for two outcomes: child
      'externalising' behaviour (a measure of rulebreaking, oppositional behaviour or
      aggression) and child 'internalising' behaviour (for example, withdrawal and
      anxiety). Meta-analysis of three studies (n = 190) providing data on
      externalising behaviour produced results that fell short of statistical
      significance (SMD -0.32; 95% CI -0.83 to 0.18, I(2) = 60%). A meta-analysis of
      two studies (n = 142) for internalising behaviour gave significant results in the
      parent training groups (SMD -0.48; 95% CI -0.84 to -0.13, I(2) = 9%). Data from a
      third study likely to have contributed to this outcome were missing, and we have
      some concerns about selective outcome reporting bias.Individual study results for
      child behaviour outcomes were mixed. Positive results on an inventory of child
      behaviour problems were reported for one small study (n = 24) with the caveat
      that results were only positive when parent training was delivered to individuals
      and not groups. In another study (n = 62), positive effects (once results were
      adjusted for demographic and baseline data) were reported for the intervention
      group on a social skills measure.The study (n = 48) that assessed parenting skill
      changes compared parent training with a nondirective parent support group.
      Statistically significant improvements were reported for the parent training
      group. Two studies (n = 142) provided data on parent stress indices that were
      suitable for combining in a meta-analysis. The results were significant for the
      'child' domain (MD -10.52; 95% CI -20.55 to -0.48) but not the 'parent' domain
      (MD -7.54; 95% CI -24.38 to 9.30). Results for this outcome from a small study (n
      = 24) suggested a long-term benefit for mothers who received the intervention at
      an individual level; in contrast, fathers benefited from short-term group
      treatment. A fourth study reported change data for within group measures of
      parental stress and found significant benefits in only one of the two active
      parent training group arms (P <= 0.01).No study reported data for academic
      achievement, adverse events or parental understanding of ADHD. AUTHORS'
      CONCLUSIONS: Parent training may have a positive effect on the behaviour of
      children with ADHD. It may also reduce parental stress and enhance parental
      confidence. However, the poor methodological quality of the included studies
      increases the risk of bias in the results. Data concerning ADHD-specific
      behaviour are ambiguous. For many important outcomes, including school
      achievement and adverse effects, data are lacking.Evidence from this review is
      not strong enough to form a basis for clinical practice guidelines. Future
      research should ensure better reporting of the study procedures and results.

PMID- 22161374
TI  - Tracheal suctioning without disconnection in intubated ventilated neonates.
AB  - BACKGROUND: Assisted mechanical ventilation is a necessity in the neonatal
      population for a variety of respiratory and surgical conditions. However, there
      are a number of potential hazards associated with this life saving intervention.
      New suctioning techniques have been introduced into clinical practice which aim
      to prevent or reduce these untoward effects. OBJECTIVES: To assess the effects of
      endotracheal suctioning without disconnection in intubated ventilated neonates.
      SEARCH METHODS: The review has drawn on the search strategy for the Cochrane
      Neonatal Review Group. A comprehensive search of Cochrane databases, MEDLINE and
      CINAHL, and the Society for Pediatric Research abstracts was undertaken by the
      review authors (July 2011). SELECTION CRITERIA: All trials that utilised random
      or quasi-random patient allocation and in which suctioning with or without
      disconnection from the ventilator was compared. DATA COLLECTION AND ANALYSIS:
      Standard methods of the Cochrane Neonatal Group were used. Each review author
      separately reviewed trials for eligibility and quality and extracted data; they
      then compared and resolved differences. Analysis was performed using the fixed
      effect model and outcomes were reported using relative risk (RR) for categorical
      data and mean difference (MD) for outcomes measured on a continuous scale. MAIN
      RESULTS: Four trials (252 infants) were included in this review. The trials
      employed a cross-over design in which suctioning with or without disconnection
      was compared. Suctioning without disconnection resulted in a reduction in
      episodes of hypoxia (typical RR 0.48, CI 95% 0.31 to 0.74; 3 studies; 241
      participants). There were also fewer infants who experienced episodes where the
      transcutaneous partial pressure of oxygen (TcPO(2)) decreased by > 10% (typical
      RR 0.39, 95% CI 0.19 to 0.82; 1 study; 11 participants). Suctioning without
      disconnection resulted in a smaller percentage change in heart rate (weighted
      mean difference (WMD) 6.77, 95% CI 4.01 to 9.52; 4 studies; 239 participants) and
      a reduction in the number of infants experiencing a decrease in heart rate by >
      10% (typical RR 0.61, CI 0.40 to 0.93; 3 studies; 52 participants).The number of
      infants having bradycardic episodes was also reduced during closed suctioning
      (typical RR 0.38, CI 95% 0.15 to 0.92; 3 studies; 241 participants). AUTHORS'
      CONCLUSIONS: There is some evidence to suggest suctioning without disconnection
      from the ventilator improves the short term outcomes; however the evidence is not
      strong enough to recommend this practice as the only method of endotracheal
      suctioning. Future research utilising larger trials needs to address the
      implications of the different techniques on ventilator associated pneumonia,
      pulmonary morbidities and neurodevelopment. Infants less than 28 weeks also need
      to be included in the trials.

PMID- 22161375
TI  - Antiplatelet agents and anticoagulants for hypertension.
AB  - BACKGROUND: Elevated systemic blood pressure results in high intravascular
      pressure but the main complications, coronary heart disease (CHD), ischaemic
      strokes and peripheral vascular disease (PVD), are related to thrombosis rather
      than haemorrhage. Some complications related to elevated blood pressure, heart
      failure or atrial fibrillation, are themselves associated with stroke and
      thromboembolism. Therefore it is important to investigate if antithrombotic
      therapy may be useful in preventing thrombosis-related complications in patients
      with elevated blood pressure. OBJECTIVES: To conduct a systematic review of the
      role of antiplatelet therapy and anticoagulation in patients with high blood
      pressure, including those with elevations in both systolic and diastolic blood
      pressure, isolated elevations of either systolic or diastolic blood pressure, to
      address the following hypotheses: (i) antiplatelet agents reduce total deaths
      and/or major thrombotic events when compared to placebo or other active
      treatment; and (ii) oral anticoagulants reduce total deaths and/or major
      thromboembolic events when compared to placebo or other active treatment. SEARCH
      METHODS: Electronic databases (MEDLINE, EMBASE, DARE, CENTRAL, Hypertension Group
      specialised register) were searched up to January 2011. The reference lists of
      papers resulting from the electronic searches and abstracts from national and
      international cardiovascular meetings were hand-searched to identify missed or
      unpublished studies. Relevant authors of studies were contacted to obtain further
      data. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with
      elevated blood pressure were included if they were of at least 3 months in
      duration and compared antithrombotic therapy with control or other active
      treatment. DATA COLLECTION AND ANALYSIS: Data were independently collected and
      verified by two reviewers. Data from different trials were pooled where
      appropriate. MAIN RESULTS: Four trials with a combined total of 44,012 patients
      met the inclusion criteria and are included in this review. Acetylsalicylic acid
      (ASA) did not reduce stroke or 'all cardiovascular events' compared to placebo in
      primary prevention patients with elevated blood pressure and no prior
      cardiovascular disease. In one large trial ASA taken for 5 years reduced
      myocardial infarction (ARR 0.5%, NNT 200), increased major haemorrhage (ARI 0.7%,
      NNT 154), and did not reduce all cause mortality or cardiovascular mortality. In
      one trial there was no significant difference between ASA and clopidogrel for the
      composite endpoint of stroke, myocardial infarction or vascular death. In two
      small trials warfarin alone or in combination with ASA did not reduce stroke or
      coronary events. The ATC meta-analysis of antiplatelet therapy for secondary
      prevention in patients with elevated blood pressure reported an absolute
      reduction in vascular events of 4.1% as compared to placebo. Data on the 10,600
      patients with elevated blood pressure from the 29 individual trials included in
      the ATC meta-analysis was requested but could not be obtained. AUTHORS'
      CONCLUSIONS: Antiplatelet therapy with ASA for primary prevention in patients
      with elevated blood pressure provides a benefit, reduction in myocardial
      infarction, which is negated by a harm of similar magnitude, increase in major
      haemorrhage.The benefit of antiplatelet therapy for secondary prevention in
      patients with elevated blood pressure is many times greater than the harm.Benefit
      has not been demonstrated for warfarin therapy alone or in combination with
      aspirin in patients with elevated blood pressure. Ticlopidine, clopidogrel and
      newer antiplatelet agents such as prasugrel and ticagrelor have not been
      sufficiently evaluated in patients with high blood pressure. Newer antithrombotic
      oral drugs such as dabigatran, rivaroxaban, apixaban and endosaban are yet to be
      tested in patients with high blood pressure.Further trials of antithrombotic
      therapy including with newer agents and complete documentation of all benefits
      and harms are required in patients with elevated blood pressure.

PMID- 22161376
TI  - Dopamine agonists for the treatment of cocaine dependence.
AB  - BACKGROUND: Cocaine dependence is a disorder for which no pharmacological
      treatment of proven efficacy exists, advances in the neurobiology could guide
      future medication development OBJECTIVES: To investigate the efficacy and
      acceptability of dopamine agonists alone or in combination with any psychosocial
      intervention for the treatment of cocaine abuse and dependence SEARCH METHODS: We
      searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register,
      PubMed, EMBASE and CINAHL, PsycINFO in June 2011 and researchers for unpublished
      trials SELECTION CRITERIA: Randomised and controlled clinical trials comparing
      dopamine agonists alone or associated with psychosocial intervention with
      placebo, no treatment, other pharmacological interventions DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trial quality and extracted data
      MAIN RESULTS: Twenty three studies, 2066 participants, met the inclusion
      criteria. Comparing any dopamine agonist versus placebo, placebo performed better
      for severity of dependence, four studies, 232 participants, SMD 0.43 (95% CI 0.15
      to 0.71), depression, five studies, 322 participants, SMD 0.42 (95% CI 0.19 to
      0.65) and abstinent at follow up RR 0.57 (95% CI 0.35 to 0.93). No statistically
      significant different for the other outcomes considered. Comparing amantadine
      versus placebo, results never gain the statistical significance, but there is a
      trend in favour of amantadine for dropouts and depression. Results on adverse
      events and depression, were in favour of placebo although the difference do not
      reach the statistical significance. Comparing bromocriptine and Ldopa/Carbidopa
      versus placebo, results never reached statistical significance. Comparing
      amantadine versus antidepressants, antidepressants performed better for
      abstinence. The other two outcomes considered did not show statistically
      significant differences although dropouts and adverse events tended to be more
      common in the antidepressant group.The quality of evidence, assessed according to
      GRADE method, may be judged as moderate for the efficacy of any dopamine agonist
      versus placebo and as moderate to high for amantadine versus placebo and versus
      antidepressants. AUTHORS' CONCLUSIONS: Current evidence from randomised
      controlled trials does not support the use of dopamine agonists for treating
      cocaine dependence. This absence of evidence may leave to clinicians the
      alternative of balancing the possible benefits against the potential adverse
      effects of the treatment. Even the potential benefit of combining a dopamine
      agonist with a more potent psychosocial intervention which was suggested by the
      previous Cochrane review (Soares 2003), is not supported by the results of this
      updated review.

PMID- 22161377
TI  - Psychological and educational interventions for preventing depression in children
      and adolescents.
AB  - BACKGROUND: Depression is common in young people, has a marked negative impact
      and is associated with self-harm and suicide. Preventing its onset would be an
      important advance in public health.   OBJECTIVES: To determine whether
      psychological or educational interventions, or both, are effective in preventing
      the onset of depressive disorder in children and adolescents. SEARCH METHODS: The
      Cochrane Depression, Anxiety and Neurosis Review Group's trials registers
      (CCDANCTR) were searched at the editorial base in July 2010. Update searches of
      MEDLINE, EMBASE, PsycINFO and ERIC were conducted by the authors in September
      2009. Conference abstracts, reference lists of included studies and reviews were
      searched and experts in the field contacted. SELECTION CRITERIA: Randomised
      controlled trials of psychological or educational prevention programmes, or both,
      compared with placebo, any comparison intervention, or no intervention for young
      people aged 5 to 19 years-old, who did not currently meet diagnostic criteria for
      depression or who were below the clinical range on standardised, validated, and
      reliable rating scales of depression, or both, were included. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed studies for inclusion and rated
      their quality. Sample sizes were adjusted to take account of cluster designs and
      multiple comparisons. We contacted study authors for additional information where
      needed.  MAIN RESULTS: Fifty-three studies including 14,406 participants were
      included in the analysis. There were only six studies with clear allocation
      concealment, participants and assessors were mostly not blind to the intervention
      or blinding was unclear so that the overall risk of bias was moderately high.
      Sixteen studies including 3240 participants reported outcomes on depressive
      diagnosis. The risk of having a depressive disorder post-intervention was reduced
      immediately compared with no intervention (15 studies; 3115 participants risk
      difference (RD) -0.09; 95% confidence interval (CI) -0.14 to -0.05; P<0.0003), at
      three to nine months (14 studies; 1842 participants; RD -0.11; 95% CI -0.16 to 
      0.06) and at 12 months (10 studies; 1750 participants; RD -0.06; 95% CI -0.11 to 
      0.01). There was no evidence for continued efficacy at 24 months (eight studies;
      2084 participant; RD -0.01; 95% CI -0.04 to 0.03) but limited evidence of
      efficacy at 36 months (two studies; 464 participants; RD -0.10; 95% CI -0.19 to 
      0.02). There was significant heterogeneity in all these findings. There was no
      evidence of efficacy in the few studies that compared intervention with placebo
      or attention controls. AUTHORS' CONCLUSIONS: There is some evidence from this
      review that targeted and universal depression prevention programmes may prevent
      the onset of depressive disorders compared with no intervention. However,
      allocation concealment is unclear in most studies, and there is heterogeneity in
      the findings. The persistence of findings suggests that this is real and not a
      placebo effect. 

PMID- 22161378
TI  - Heroin maintenance for chronic heroin-dependent individuals.
AB  - BACKGROUND: Several types of medications have been used for stabilizing heroin
      users: Methadone, Buprenorphine and levo-alpha-acetyl-methadol (LAAM.) The
      present review focuses on the prescription of heroin to heroin-dependent
      individuals. OBJECTIVES: To compare heroin maintenance to methadone or other
      substitution treatments for opioid dependence regarding: efficacy and
      acceptability, retaining patients in treatment, reducing the use of illicit
      substances, and improving health and social functioning. SEARCH METHODS: A review
      of the Cochrane Central Register of Trials (The Cochrane Library Issue 1, 2005),
      MEDLINE (1966 to november 2009), EMBASE (1980 to 2005) and CINAHL until 2005 (on
      OVID) was conducted. Personal communications with researchers in the field of
      heroin prescription identified ongoing trials. SELECTION CRITERIA: Randomised
      controlled trials of heroin maintenance treatment (alone or combined with
      methadone) compared with any other pharmacological treatment for heroin-dependent
      individuals. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. MAIN RESULTS: Eight studies involving 2007
      patients met the inclusion criteria. Five studies compared supervised injected
      heroin plus flexible dosages of methadone treatment to oral methadone only and
      showed that heroin helps patients to remain in treatment (valid data from 4
      studies, N=1388 Risk Ratio 1.44 (95%CI 1.19-1.75) heterogeneity P=0.03), and to
      reduce use of illicit drugs. Maintenance with supervised injected heroin has a
      not statistically significant protective effect on mortality (4 studies, N=1477
      Risk Ratio 0.65 (95% CI 0.25-1.69) heterogeneity P=0.89), but it exposes at a
      greater risk of adverse events related to study medication (3 studies N=373 Risk
      Ratio 13.50 (95% CI 2.55-71.53) heterogeneity P=0.52). Results on criminal
      activity and incarceration were not possible to be pooled but where the outcome
      were measured results of single studies do provide evidence that heroin provision
      can reduce criminal activity and incarceration/imprisonment. Social functioning
      improved in all the intervention groups with heroin groups having slightly better
      results. If all the studies comparing heroin provision in any conditions vs any
      other treatment are pooled the direction of effect remain in favour of heroin.
      AUTHORS' CONCLUSIONS: The available evidence suggests an added value of heroin
      prescribed alongside flexible doses of methadone for long-term, treatment
      refractory, opioid users, to reach a decrease in the use of illicit substances,
      involvement in criminal activity and incarceration, a possible reduction in
      mortaliity; and an increase in retention in treatment. Due to the higher rate of
      serious adverse events, heroin prescription should remain a treatment for people
      who are currently or have in the past failed maintenance treatment, and it should
      be provided in clinical settings where proper follow-up is ensured.

PMID- 22161379
TI  - Corticosteroids for treating hypotension in preterm infants.
AB  - BACKGROUND: Systemic hypotension is a relatively common complication of preterm
      birth and is associated with periventricular haemorrhage, periventricular white
      matter injury and adverse neurodevelopmental outcome. Corticosteroid treatment
      has been used as an alternative or an adjunct to conventional treatment with
      volume expansion and vasopressor/inotropic therapy. OBJECTIVES: To determine the
      effectiveness and safety of corticosteroids used either as primary treatment of
      hypotension or for the treatment of refractory hypotension in preterm infants.
      SEARCH METHODS: Randomized or quasi-randomised controlled trials were identified
      by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 2, 2011), MEDLINE (1996 to Jan 2011), EMBASE (1974 to Jan
      2011), CINAHL (1981 to 2011), reference lists of published papers and abstracts
      from the Pediatric Academic Societies and the European Society for Pediatric
      Research meetings published in Pediatric Research (1995 to 2011). SELECTION
      CRITERIA: We included all randomised or quasi-randomised controlled trials
      investigating the effect of corticosteroid therapy in the treatment of
      hypotension in preterm infants (< 37 weeks gestation) less than 28 days old.
      Studies using corticosteroids as primary treatment were included as well as
      studies using corticosteroids in babies with hypotension resistant to
      inotropes/pressors and volume therapy. We included studies comparing
      oral/intravenous corticosteroids with placebo, other drugs used for providing
      cardiovascular support or no therapy in this review. DATA COLLECTION AND
      ANALYSIS: Methodological quality of eligible studies was assessed according to
      the methods used for minimising selection bias, performance bias, attrition bias
      and detection bias. Studies that evaluated corticosteroids (1) as primary
      treatment for hypotension or (2) for refractory hypotension unresponsive to prior
      use of inotropes/pressors and volume therapy, were analysed using separate
      comparisons. Data were analysed using the standard methods of the Neonatal Review
      Group using Rev Man 5.1.2. Treatment effect was analysed using relative risk,
      risk reduction, number needed to treat for categorical outcomes and weighted mean
      difference for outcomes measured on a continuous scale, with 95% confidence
      intervals. MAIN RESULTS: Four studies were included in this review enrolling a
      total of 123 babies. In one study, persistent hypotension was more common in
      hydrocortisone treated infants as compared to those who received dopamine as
      primary treatment for hypotension (RR 8.2, 95% CI 0.47 to 142.6; RD 0.19, 95% CI
      0.01 to 0.37). In two studies comparing steroid versus placebo, persistent
      hypotension (defined as a continuing need for inotrope infusion) was less common
      in steroid treated infants as compared to controls who received placebo for
      refractory hypotension (RR 0.35, 95% CI 0.19 to 0.65; RD -0.47, 95% CI - 0.68 to 
      0.26; NNT = 2.1, 95% CI 1.47, 3.8). There were no statistically significant
      effects on any other short or long-term outcome. A further two studies that have
      only been published in abstract form to date, may be eligible for inclusion in a
      future update of this review. AUTHORS' CONCLUSIONS: Hydrocortisone may be as
      effective as dopamine when used as a primary treatment for hypotension. But the
      long term safety data on the use of hydrocortisone in this manner is
      unknown.Steroids are effective in treatment of refractory hypotension in preterm
      infants without an increase in short term adverse consequences. However, long
      term safety or benefit data is lacking. With long term benefit or safety data
      lacking steroids cannot be recommended routinely for the treatment of hypotension
      in preterm infants.

PMID- 22161380
TI  - Auditory integration training and other sound therapies for autism spectrum
      disorders (ASD).
AB  - BACKGROUND: Auditory integration therapy was developed as a technique for
      improving abnormal sound sensitivity in individuals with behavioural disorders
      including autism spectrum disorders. Other sound therapies bearing similarities
      to auditory integration therapy include the Tomatis Method and Samonas Sound
      Therapy. OBJECTIVES: To determine the effectiveness of auditory integration
      therapy or other methods of sound therapy in individuals with autism spectrum
      disorders. SEARCH METHODS: For this update, we searched the following databases
      in September 2010: CENTRAL (2010, Issue 2), MEDLINE (1950 to September week 2,
      2010), EMBASE (1980 to Week 38, 2010), CINAHL (1937 to current), PsycINFO (1887
      to current), ERIC (1966 to current), LILACS (September 2010) and the reference
      lists of published papers. One new study was found for inclusion. SELECTION
      CRITERIA: Randomised controlled trials involving adults or children with autism
      spectrum disorders. Treatment was auditory integration therapy or other sound
      therapies involving listening to music modified by filtering and modulation.
      Control groups could involve no treatment, a waiting list, usual therapy or a
      placebo equivalent. The outcomes were changes in core and associated features of
      autism spectrum disorders, auditory processing, quality of life and adverse
      events. DATA COLLECTION AND ANALYSIS: Two independent review authors performed
      data extraction. All outcome data in the included papers were continuous. We
      calculated point estimates and standard errors from t-test scores and post
      intervention means. Meta-analysis was inappropriate for the available data. MAIN
      RESULTS: We identified six randomised comtrolled trials of auditory integration
      therapy and one of Tomatis therapy, involving a total of 182 individuals aged
      three to 39 years. Two were cross-over trials. Five trials had fewer than 20
      participants. Allocation concealment was inadequate for all studies. Twenty
      different outcome measures were used and only two outcomes were used by three or
      more studies. Meta-analysis was not possible due to very high heterogeneity or
      the presentation of data in unusable forms. Three studies (Bettison 1996; Zollweg
      1997; Mudford 2000) did not demonstrate any benefit of auditory integration
      therapy over control conditions. Three studies (Veale 1993; Rimland 1995; Edelson
      1999) reported improvements at three months for the auditory integration therapy
      group based on the Aberrant Behaviour Checklist, but they used a total score
      rather than subgroup scores, which is of questionable validity, and Veale's
      results did not reach statistical significance. Rimland 1995 also reported
      improvements at three months in the auditory integration therapy group for the
      Aberrant Behaviour Checklist subgroup scores. The study addressing Tomatis
      therapy (Corbett 2008) described an improvement in language with no difference
      between treatment and control conditions and did not report on the behavioural
      outcomes that were used in the auditory integration therapy trials. AUTHORS'
      CONCLUSIONS: There is no evidence that auditory integration therapy or other
      sound therapies are effective as treatments for autism spectrum disorders. As
      synthesis of existing data has been limited by the disparate outcome measures
      used between studies, there is not sufficient evidence to prove that this
      treatment is not effective. However, of the seven studies including 182
      participants that have been reported to date, only two (with an author in
      common), involving a total of 35 participants, report statistically significant
      improvements in the auditory intergration therapy group and for only two outcome
      measures (Aberrant Behaviour Checklist and Fisher's Auditory Problems Checklist).
      As such, there is no evidence to support the use of auditory integration therapy
      at this time.

PMID- 22161381
TI  - Oral rehydration salt solution for treating cholera: <= 270 mOsm/L solutions vs
      >= 310 mOsm/L solutions.
AB  - BACKGROUND: Oral rehydration solution (ORS) is used to treat the dehydration
      caused by diarrhoeal diseases, including cholera. ORS formulations with an
      osmolarity (a measure of solute concentration) of <= 270 mOsm/L (ORS <= 270) are
      safe and more effective than ORS formulations with an osmolarity of >= 310 mOsm/L
      (ORS >= 310) for treating non-cholera diarrhoea. As cholera causes rapid
      electrolyte loss, it is important to know if these benefits are similar for
      people suffering from cholera. OBJECTIVES: To compare the safety and efficacy of
      ORS <=270 with ORS >= 310 for treating dehydration due to cholera. SEARCH
      METHODS: We searched the Cochrane Infectious Disease Group Specialized Register
      (April 2011), CENTRAL (The Cochrane Library Issue 4, 2011), MEDLINE (1966 to
      April 2011), EMBASE (1974 to April 2011), and LILACS (1982 to April 2011). We
      also contacted organizations and searched reference lists. SELECTION CRITERIA:
      Randomized controlled trials comparing ORS <= 270 with ORS >= 310 for treating
      adults and children with acute diarrhoea due to cholera. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently applied eligibility criteria, assessed
      trial quality, and extracted data. We pooled dichotomous data using risk ratio
      (RR), pooled continuous data using mean difference (MD) or the standardized mean
      difference (SMD), and presented the results with 95% confidence intervals (CI).
      MAIN RESULTS: For glucose-based ORS, seven trials (718 participants) met the
      inclusion criteria. Biochemical hyponatraemia (blood sodium levels < 130 mmol/L)
      was more common with ORS <= 270 (RR 1.67, CI 1.09 to 2.57; 465 participants, four
      trials), while a higher level of severe biochemical hyponatraemia (blood sodium
      levels < 125 mmol/L) in the same group was not significant (RR 1.58, CI 0.62 to
      4.04; 465 participants, four trials). No instances of symptomatic hyponatraemia
      or death were noted in the trials that intended to record them. We found no
      statistically significant difference in the need for unscheduled intravenous
      infusion. Analyses separating children and adults showed no obvious trends.Two
      trials also examined rice-based ORS. In the ORS <= 270 group, duration of
      diarrhoea was shorter (MD -11.42 hours, CI -13.80 to -9.04; 102 participants, two
      trials). AUTHORS' CONCLUSIONS: In people with cholera, ORS <= 270 is associated
      with biochemical hyponatraemia when compared with ORS >= 310, but there are no
      differences in terms of other outcomes. Although this risk does not appear to be
      associated with any serious consequences, the total patient experience in
      existing trials is small. Under wider practice conditions, especially where
      patient monitoring is difficult, caution is warranted.

PMID- 22161382
TI  - Conservative prevention and management of pelvic organ prolapse in women.
AB  - BACKGROUND: Pelvic organ prolapse is common, and some degree of prolapse is seen
      in 50% of parous women. Women with prolapse can experience a variety of pelvic
      floor symptoms. Treatments include surgery, mechanical devices and conservative
      management. Conservative management approaches, such as giving lifestyle advice
      and delivering pelvic floor muscle training (PFMT), are often used in cases of
      mild to moderate prolapse. This is an update of a Cochrane review first published
      in 2004, and previously updated in 2006. OBJECTIVES: To determine the effects of
      conservative management (physical and lifestyle interventions) for the prevention
      or treatment of pelvic organ prolapse in comparison with no treatment or other
      treatment options (such as mechanical devices or surgery). SEARCH METHODS: We
      searched the Cochrane Incontinence Group Specialised Trials Register (searched 6
      May 2010), EMBASE (1 January 1996 to 6 May 2010), CINAHL (1 January 1982 to 10
      May 2010), PEDro (January 2009), the UK National Research Register (January
      2009), ClinicalTrials.gov (April 2009), Current Controlled Trials register (April
      2009), CENTRAL (Issue 1, 2009) and ZETOC (January 2009) and the reference lists
      of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised trials
      in women with pelvic organ prolapse that included a physical or lifestyle
      intervention in at least one arm of the trial. DATA COLLECTION AND ANALYSIS: Two
      reviewers assessed all trials for inclusion/exclusion and methodological quality.
      Data were extracted by the lead reviewer onto a standard form and cross checked
      by another. Disagreements were resolved by discussion. Data were processed as
      described in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN
      RESULTS: Six trials were included; three of these trials are new to this update.
      Four trials were small (less than 25 women per arm) and two had moderate to high
      risk of bias. Four trials compared PFMT as a treatment for prolapse against a
      control group (n = 857 women); two trials included women having surgery for
      prolapse and compared PFMT as an adjunct to surgery versus surgery alone (n = 118
      women).PFMT versus controlThere was a significant risk of bias in two out four
      trials in this comparison. Prolapse symptoms and women's reports of treatment
      outcomes (primary outcomes) were measured differently in the three trials where
      this was reported: all three indicated greater improvement in symptoms in the
      PFMT group compared to the control group. Pooling data on severity of prolapse
      from two trials indicated that PFMT increases the chance of an improvement in
      prolapse stage by 17% compared to no PFMT. The two trials which measured pelvic
      floor muscle function found better function (or improvement in function) in the
      PFMT group compared to the control group; measurements were not known to be
      blinded. Two out of three trials which measured urinary outcomes (urodynamics,
      frequency and bother of symptoms, or symptom score) reported differences between
      groups in favour of the PFMT group. One trial reported bowel outcomes, showing
      less frequency and bother with symptoms in the PFMT group compared to the control
      group.PFMT supplementing surgery versus surgery aloneBoth trials were small and
      neither measured prolapse-specific outcomes. Pelvic floor muscle function
      findings differed between the trials: one found no difference between trial
      groups in muscle strength, whilst the other found a benefit for the PFMT group in
      terms of stronger muscles. Similarly findings relating to urinary outcomes were
      contradictory: one trial found no difference in symptom score change between
      groups, whilst the other found more improvement in urinary symptoms and a
      reduction in diurnal frequency in the PFMT group compared to the control group.
      AUTHORS' CONCLUSIONS: There is now some evidence available indicating a positive
      effect of PFMT for prolapse symptoms and severity. The largest most rigorous
      trial to date suggests that six months of supervised PFMT has benefits in terms
      of anatomical and symptom improvement (if symptomatic) immediately post
      intervention. Further evidence relating to effectiveness and cost-effectiveness
      of PFMT, of different intensities, for symptomatic prolapse in the medium and
      long term is needed. A large trial of PFMT supplementing surgery is needed to
      give clear evidence about the usefulness of combining these treatments. Other
      comparisons which have not been addressed in trials to date and warrant
      consideration include those involving lifestyle change interventions, and trials
      aimed at prolapse prevention.

PMID- 22161383
TI  - Music therapy for people with schizophrenia and schizophrenia-like disorders.
AB  - BACKGROUND: Music therapy is a therapeutic method that uses musical interaction
      as a means of communication and expression. The aim of the therapy is to help
      people with serious mental disorders to develop relationships and to address
      issues they may not be able to using words alone. OBJECTIVES: To review the
      effects of music therapy, or music therapy added to standard care, compared with
      'placebo' therapy, standard care or no treatment for people with serious mental
      disorders such as schizophrenia. SEARCH METHODS: We searched the Cochrane
      Schizophrenia Group Trials Register (December 2010) and supplemented this by
      contacting relevant study authors, handsearching of music therapy journals and
      manual searches of reference lists. SELECTION CRITERIA: All randomised controlled
      trials (RCTs) that compared music therapy with standard care, placebo therapy, or
      no treatment. DATA COLLECTION AND ANALYSIS: Studies were reliably selected,
      quality assessed and data extracted. We excluded data where more than 30% of
      participants in any group were lost to follow-up. We synthesised non-skewed
      continuous endpoint data from valid scales using a standardised mean difference
      (SMD). If statistical heterogeneity was found, we examined treatment 'dosage' and
      treatment approach as possible sources of heterogeneity. MAIN RESULTS: We
      included eight studies (total 483 participants). These examined effects of music
      therapy over the short- to medium-term (one to four months), with treatment
      'dosage' varying from seven to 78 sessions. Music therapy added to standard care
      was superior to standard care for global state (medium-term, 1 RCT, n = 72, RR
      0.10 95% CI 0.03 to 0.31, NNT 2 95% CI 1.2 to 2.2). Continuous data identified
      good effects on negative symptoms (4 RCTs, n = 240, SMD average endpoint Scale
      for the Assessment of Negative Symptoms (SANS) -0.74 95% CI -1.00 to -0.47);
      general mental state (1 RCT, n = 69, SMD average endpoint Positive and Negative
      Symptoms Scale (PANSS) -0.36 95% CI -0.85 to 0.12; 2 RCTs, n=100, SMD average
      endpoint Brief Psychiatric Rating Scale (BPRS) -0.73 95% CI -1.16 to -0.31);
      depression (2 RCTs, n = 90, SMD average endpoint Self-Rating Depression Scale
      (SDS) -0.63 95% CI -1.06 to -0.21; 1 RCT, n = 30, SMD average endpoint Hamilton
      Depression Scale (Ham-D) -0.52 95% CI -1.25 to -0.21 ); and anxiety (1 RCT, n =
      60, SMD average endpoint SAS -0.61 95% CI -1.13 to -0.09). Positive effects were
      also found for social functioning (1 RCT, n = 70, SMD average endpoint Social
      Disability Schedule for Inpatients (SDSI) score -0.78 95% CI -1.27 to -0.28).
      Furthermore, some aspects of cognitive functioning and behaviour seem to develop
      positively through music therapy. Effects, however, were inconsistent across
      studies and depended on the number of music therapy sessions as well as the
      quality of the music therapy provided. AUTHORS' CONCLUSIONS: Music therapy as an
      addition to standard care helps people with schizophrenia to improve their global
      state, mental state (including negative symptoms) and social functioning if a
      sufficient number of music therapy sessions are provided by qualified music
      therapists. Further research should especially address the long-term effects of
      music therapy, dose-response relationships, as well as the relevance of outcomes
      measures in relation to music therapy.

PMID- 22161385
TI  - Combination fluticasone and salmeterol versus fixed dose combination budesonide
      and formoterol for chronic asthma in adults and children.
AB  - BACKGROUND: Long-acting beta-agonists are a common second line treatment in
      people with asthma inadequately controlled with inhaled corticosteroids. Single
      device inhalers combine a long-acting beta-agonist with an inhaled steroid
      delivering both drugs as a maintenance treatment regimen. This updated review
      compares two fixed-dose options, fluticasone/salmeterol FP/SALand
      budesonide/formoterol, since this comparison represents a common therapeutic
      choice. OBJECTIVES: To assess the relative effects of fluticasone/salmeterol and
      budesonide/formoterol in people with asthma. SEARCH METHODS: We searched the
      Cochrane Airways Group register of trials with prespecified terms. We performed
      additional hand searching of manufacturers' web sites and online trial
      registries. Search results are current to June 2011. SELECTION CRITERIA: We
      included randomised studies comparing fixed dose fluticasone/salmeterol and
      budesonide/formoterol in adults or children with a diagnosis of asthma. Treatment
      in the studies had to last for a minimum of 12 weeks. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed studies for inclusion in the review.
      We combined continuous data outcomes with a mean difference (MD), and dichotomous
      data outcomes with an odds ratio (OR). We assessed the quality of the evidence
      using the Grading of Recommendations Assessment, Development and Evaluation
      (GRADE) system. MAIN RESULTS: Five studies met the review entry criteria (5537
      adults). Study populations entered the studies having previously been treated
      with inhaled steroids and had moderate or mild airway obstruction (mean FEV(1)
      predicted between 65% and 84% at baseline). Most of the studies assessed
      treatment over a period of six months. The studies were at a low risk of
      selection and performance/detection bias, although we could not determine whether
      missing data had an impact on the results. Availablility of outcome data was
      satisfactory.Primary outcomesThe odds ratio for exacerbations requiring oral
      steroids was lower with fluticasone/salmeterol but did not reach statistical
      significance (OR 0.89, 95% confidence interval (CI) 0.74 to 1.07, four studies, N
      = 4949). With an assumed risk with budesonide/formoterol of 106/1000 participants
      requiring oral steroids, treatment with fluticasone/salmeterol would lead to
      between 25 fewer and seven more people per 1000 experiencing a course of oral
      steroids. Although the odds of hospital admission was higher with
      fluticasone/salmeterol, this did not reach statistical significance (OR 1.29, 95%
      CI 0.68 to 2.47, four studies, 4879 participants). With an assumed risk in the
      budesonide/formoterol of 7/1000, between two fewer and 10 more people per 1000
      would be hospitalised on fluticasone/salmeterol. The odds of a serious adverse
      event related to asthma was higher with fluticasone/salmeterol but did not differ
      significantly between treatments (OR 1.47, 95% CI 0.75 to 2.86, three studies,
      4054 participants). With an assumed risk in the budesonide/formoterol of 7/1000,
      between two fewer and 13 more people per 1000 would experience a serious adverse
      event on fluticasone/salmeterol.Secondary outcomesLung function outcomes,
      symptoms, rescue medication, composite of exacerbations leading to either
      emergency department visit or hospital admission, withdrawals and adverse events
      did not differ statistically between treatments. Assessment of quality of life
      was limited to two studies, both of which gave results that did not reach
      statistical significance. One study reported one death out of 1000 participants
      on fluticasone/salmeterol and no deaths in a similar number of participants
      treated with budesonide/formoterol. No deaths were reported in the other studies.
      AUTHORS' CONCLUSIONS: Statistical imprecision in the effect estimates for
      exacerbations and serious adverse events do not enable us to conclude that either
      therapy is superior. The uncertainty around the effect estimates justify further
      trials to provide more definitive conclusions; the overall quality of evidence
      based on GRADE recommendations for the three primary outcomes and withdrawals due
      to serious adverse events was moderate. We rated the quality of evidence for
      mortality to be low. Results for lung function outcomes showed that the drugs
      were sufficiently similar that further research is unlikely to change the
      effects. No trials were identified in the under-12s and research in this
      population is a high priority. Evaluation of quality of life is a priority for
      future research.

PMID- 22161384
TI  - Day hospital versus admission for acute psychiatric disorders.
AB  - BACKGROUND: Inpatient treatment is an expensive way of caring for people with
      acute psychiatric disorders. It has been proposed that many of those currently
      treated as inpatients could be cared for in acute psychiatric day hospitals.
      OBJECTIVES: To assess the effects of day hospital versus inpatient care for
      people with acute psychiatric disorders. SEARCH METHODS: We searched the Cochrane
      Schizophrenia Group Trials Register (June 2010) which is based on regular
      searches of MEDLINE, EMBASE, CINAHL and PsycINFO. We approached trialists to
      identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials of
      day hospital versus inpatient care, for people with acute psychiatric disorders.
      Studies were ineligible if a majority of participants were under 18 or over 65,
      or had a primary diagnosis of substance abuse or organic brain disorder. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted and cross
      checked data. We calculated risk ratios (RR) and 95% confidence intervals (CI)
      for dichotomous data. We calculated weighted or standardised means for continuous
      data. Day hospital trials tend to present similar outcomes in slightly different
      formats, making it difficult to synthesise data. We therefore sought individual
      patient data so that we could re-analyse outcomes in a common format. MAIN
      RESULTS: Ten trials (involving 2685 people) met the inclusion criteria. We
      obtained individual patient data for four trials (involving 646 people). We found
      no difference in the number lost to follow-up by one year between day hospital
      care and inpatient care (5 RCTs, n = 1694, RR 0.94 CI 0.82 to 1.08). There is
      moderate evidence that the duration of index admission is longer for patients in
      day hospital care than inpatient care (4 RCTs, n = 1582, WMD 27.47 CI 3.96 to
      50.98). There is very low evidence that the duration of day patient care
      (adjusted days/month) is longer for patients in day hospital care than inpatient
      care (3 RCTs, n = 265, WMD 2.34 days/month CI 1.97 to 2.70). There is no
      difference between day hospital care and inpatient care for the being readmitted
      to in/day patient care after discharge (5 RCTs, n = 667, RR 0.91 CI 0.72 to
      1.15). It is likely that there is no difference between day hospital care and
      inpatient care for being unemployed at the end of the study (1 RCT, n = 179, RR
      0.88 CI 0.66 to 1.19), for quality of life (1 RCT, n = 1117, MD 0.01 CI -0.13 to
      0.15) or for treatment satisfaction (1 RCT, n = 1117, MD 0.06 CI -0.18 to 0.30).
      AUTHORS' CONCLUSIONS: Caring for people in acute day hospitals is as effective as
      inpatient care in treating acutely ill psychiatric patients. However, further
      data are still needed on the cost effectiveness of day hospitals.

PMID- 22161386
TI  - Catheter policies for management of long term voiding problems in adults with
      neurogenic bladder disorders.
AB  - BACKGROUND: Management of the neurogenic bladder has the primary objectives of
      maintaining continence, ensuring low bladder pressure (to avoid renal damage) and
      avoiding or minimising infection. Options include intermittent urethral
      catheterisation, indwelling urethral or suprapubic catheterisation, timed
      voiding, use of external catheter (for men), drug treatment, augmentation
      cystoplasty and urinary diversion. OBJECTIVES: To assess the effects of using
      different types of urinary catheters and external (sheath) catheters in managing
      the neurogenic bladder, compared to alternative management strategies or
      interventions. SEARCH METHODS: We searched the Cochrane Incontinence Group
      Specialised Register (searched 1 November 2011), which contains trials identified
      from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and
      CINAHL, and handsearching of journals and conference proceedings. We sought
      additional trials from other sources such as reference lists of relevant articles
      and contacting consultants in Spinal Cord Injury Centres throughout the United
      Kingdom. SELECTION CRITERIA: All randomised and quasi-randomised controlled
      trials comparing methods of using catheters to manage urinary voiding in people
      with neurogenic bladder. DATA COLLECTION AND ANALYSIS: Abstracts were
      independently inspected by the reviewers and full papers were obtained where
      necessary. MAIN RESULTS: Approximately 400 studies were scrutinised. No trials
      were found that met the inclusion criteria, and five studies were excluded from
      the review. AUTHORS' CONCLUSIONS: Despite a comprehensive search no evidence from
      randomised or quasi-randomised controlled trials was found. It was not possible
      to draw any conclusions regarding the use of different types of catheter in
      managing the neurogenic bladder.

PMID- 22161387
TI  - Oxcarbazepine for acute affective episodes in bipolar disorder.
AB  - BACKGROUND: Oxcarbazepine, a keto derivative of the 'mood stabiliser'
      carbamazepine, may have efficacy in the treatment of acute episodes of bipolar
      disorder. Potentially, it may offer pharmacokinetic advantages over
      carbamazepine. OBJECTIVES: To review the efficacy and acceptability of
      oxcarbazepine compared to placebo and other agents in the treatment of acute
      bipolar episodes including mania, mixed episodes and depression. SEARCH METHODS:
      Electronic databases were searched up to 2 September 2011. Specialist journals
      and conference proceedings were handsearched. Authors, experts in the field and
      pharmaceutical companies were contacted requesting information on published and
      unpublished trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) which
      compared oxcarbazepine with placebo or alternative agents, where the stated
      intent of intervention was the acute treatment of bipolar affective disorder were
      sought. Participants with bipolar disorder of either sex and of all ages were
      included. DATA COLLECTION AND ANALYSIS: Data were extracted from the original
      reports individually by two review authors. For dichotomous data, odds ratios
      (ORs) were calculated with 95% confidence intervals (CI). Continuous data were
      analysed using standardised mean differences (with 95% CI). MAIN RESULTS: Seven
      studies were included in the analysis (368 participants in total). All were on
      mania, hypomania, mixed episodes or rapid-cycling disorder. Overall, their
      methodological quality was relatively low.There was no difference in the primary
      outcome analysis - a fall of  50% or more on the Young Mania Rating Scale (YMRS) 
      between oxcarbazepine and placebo (N=1, n=110, OR =2.10, 95% CI 0.94 to 4.73) in
      one study, conducted in children; no studies were available in adult
      participants.In comparison with other mood stabilisers, there was no difference
      between oxcarbazepine and valproate as an antimanic agent using the primary
      outcome (50% or more fall in YMRS, OR=0.44, 95% CI 0.10 to 1.97, 1 study, n=60,
      P=0.273) or the secondary outcome measure (differences in YMRS between the two
      groups, SMD=0.18, 95% CI -0.24 to 0.59, 2 studies, n=90, P=0.40). No primary or
      secondary efficacy outcome measures were found comparing oxcarbazepine with
      lithium monotherapy.As an adjunctive treatment to lithium, oxcarbazepine reduced
      depression rating scale scores more than carbamazepine in a group of manic
      participants on the Montgomery-Asberg Depression Rating Scale (MADRS) (SMD=-
      1.12, 95% CI -1.71 to -0.53, 1 study, n=52, P=0.0002) and on the Hamilton
      Depression Rating Scale (HDRS) (SMD=- 0.77, 95% CI -1.35 to -0.20, 1 study, n=52,
      P=0.008).There was a higher incidence of adverse effects, particularly
      neuropsychiatric, in participants randomised to oxcarbazepine compared to those
      on placebo (1 study, n=115, 17% to 39% of participants on oxcarbazepine had at
      least one such event compared to 7% to 10% on placebo).There was no difference in
      adverse events rates between oxcarbazepine and other mood stabilisers or
      haloperidol. AUTHORS' CONCLUSIONS: Currently, there are insufficient trials of
      adequate methodological quality on oxcarbazepine in the acute treatment of
      bipolar disorder to inform us on its efficacy and acceptability. Studies
      predominantly examine the treatment of mania: there are data from subgroup
      analysis on mixed affective, hypomania and rapid-cycling states.From the few
      studies included in this review, oxcarbazepine did not differ in efficacy
      compared to placebo in children and adolescents. It did not differ from other
      active agents in adults. It may have a poorer tolerability profile compared to
      placebo. No data were found on outcomes relevant to patients and clinicians, such
      as length of hospital admission.  There is a need for adequately powered
      randomised controlled trials of good methodological quality to inform us of the
      therapeutic potential of oxcarbazepine across the spectrum of acute episodes in
      bipolar disorder.

PMID- 22161389
TI  - Tiagabine in the maintenance treatment of bipolar disorder.
AB  - BACKGROUND: Tiagabine, an anticonvulsant, has been reported to have efficacy in
      prophylactic treatment of bipolar disorder in case reports and in case series.
      OBJECTIVES: To assess the efficacy and acceptability of tiagabine, relative to
      placebo, and other agents in the prevention or attenuation, or both, of episodes
      of bipolar disorder in adults. The efficacy and acceptability of tiagabine were
      considered in terms of mood symptoms, mortality, general health, social
      functioning, adverse effects and overall acceptability to participants. SEARCH
      METHODS: The Cochrane Collaboration Depression, Anxiety and Neurosis review
      group's specialised registers (CCDANCTR-Studies and CCDANCTR-References) were
      searched to 1 October 2011. These registers contains relevant randomised
      controlled trials from: The Cochrane Library (all years to date), EMBASE, (1974
      to date) MEDLINE (1950 to date) and PsycINFO (1967 to date). Reference lists of
      relevant papers and major textbooks of affective disorder were examined. Authors,
      other experts in the field and pharmaceutical companies were contacted for
      knowledge of suitable published or unpublished trials. Specialist journals and
      conference proceedings were handsearched. SELECTION CRITERIA: Randomised
      controlled trials of tiagabine versus placebo, alternative mood stabilisers or
      antipsychotics, for the maintenance treatment of bipolar disorder in adults, male
      and female, aged 18 to 74 years. DATA COLLECTION AND ANALYSIS: Data were to be
      extracted from the original reports of included studies independently by two
      authors. The main outcomes to be assessed were:(1) the efficacy of tiagabine
      treatment in preventing or attenuating further episodes of bipolar disorder,
      including its efficacy in rapid cycling disorder; (2) the acceptability of
      tiagabine treatment to participants; (3) the prevalence of side effects; and (4)
      mortality, if any, on tiagabine treatment.Outcomes concerning relapse or
      recurrence were to be analysed excluding data from studies using discontinuation
      protocols, which were to be analysed separately. Subgroup analyses were to be
      performed to examine the effects of tiagabine treatment in rapid cycling bipolar
      disorder and previous mood stabiliser non-responders. Data were to be analysed
      using Review Manager 5. MAIN RESULTS: No randomised controlled trials of
      tiagabine in the maintenance treatment of bipolar disorder were found. AUTHORS'
      CONCLUSIONS: There is an insufficient methodologically rigorous evidence base to
      draw any conclusions regarding the use of tiagabine in the maintenance treatment
      of bipolar disorder. There is a need for randomised controlled trials examining
      the therapeutic potential of this agent in bipolar disorder. There have been some
      reports of syncope or seizures, or both, when tiagabine has been used for the
      acute treatment of mania. It needs to be established if such adverse effects
      occur in the maintenance phase as well.

PMID- 22161388
TI  - Interventions to slow progression of myopia in children.
AB  - BACKGROUND: Nearsightedness (myopia) causes blurry vision when looking at distant
      objects. Highly nearsighted people are at greater risk of several vision
      threatening problems such as retinal detachments, choroidal atrophy, cataracts
      and glaucoma. Interventions that have been explored to slow the progression of
      myopia include bifocal spectacles, cycloplegic drops, intraocular pressure
      lowering drugs, muscarinic receptor antagonists and contact lenses. The purpose
      of this review was to systematically assess the effectiveness of strategies to
      control progression of myopia in children. OBJECTIVES: To assess the effects of
      several types of interventions, including eye drops, undercorrection of
      nearsightedness, multifocal spectacles and contact lenses, on the progression of
      nearsightedness in myopic children younger than 18 years. We compared the
      interventions of interest with each other, to single vision lenses (SVLs)
      (spectacles), placebo or no treatment. SEARCH METHODS: We searched CENTRAL (which
      contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane
      Library 2011, Issue 10), MEDLINE (January 1950 to October 2011), EMBASE (January
      1980 to October 2011), Latin American and Caribbean Literature on Health Sciences
      (LILACS) (January 1982 to October 2011), the metaRegister of Controlled Trials
      (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov
      (http://clinicaltrials.gov). There were no date or language restrictions in the
      electronic searches for trials. The electronic databases were last searched on 11
      October 2011. We also searched the reference lists and Science Citation Index for
      additional, potentially relevant studies. SELECTION CRITERIA: We included
      randomized controlled trials (RCTs) in which participants were treated with
      spectacles, contact lenses or pharmaceutical agents for the purpose of
      controlling progression of myopia. We excluded trials where participants were
      older than 18 years at baseline or participants had less than -0.25 diopters (D)
      spherical equivalent myopia. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted data and assessed the risk of bias for each included
      study. When possible, we analyzed data with the inverse variance method using a
      fixed-effect or random-effects model, depending on the number of studies and
      amount of heterogeneity detected. MAIN RESULTS: We included 23 studies (4696
      total participants) in this review, with 17 of these studies included in
      quantitative analysis. Since we only included RCTs in the review, the studies
      were generally at low risk of bias for selection bias. Undercorrection of myopia
      was found to increase myopia progression slightly in two studies; children who
      were undercorrected progressed on average 0.15 D (95% confidence interval (CI) 
      0.29 to 0.00) more than the fully corrected SVLs wearers at one year. Rigid gas
      permeable contact lenses (RGPCLs) were found to have no evidence of effect on
      myopic eye growth in two studies (no meta-analysis due to heterogeneity between
      studies). Progressive addition lenses (PALs), reported in four studies, and
      bifocal spectacles, reported in four studies, were found to yield a small slowing
      of myopia progression. For seven studies with quantitative data at one year,
      children wearing multifocal lenses, either PALs or bifocals, progressed on
      average 0.16 D (95% CI 0.07 to 0.25) less than children wearing SVLs. The largest
      positive effects for slowing myopia progression were exhibited by anti-muscarinic
      medications. At one year, children receiving pirenzepine gel (two studies),
      cyclopentolate eye drops (one study), or atropine eye drops (two studies) showed
      significantly less myopic progression compared with children receiving placebo
      (mean differences (MD) 0.31 (95% CI 0.17 to 0.44), 0.34 (95% CI 0.08 to 0.60),
      and 0.80 (95% CI 0.70 to 0.90), respectively). AUTHORS' CONCLUSIONS: The most
      likely effective treatment to slow myopia progression thus far is anti-muscarinic
      topical medication. However, side effects of these medications include light
      sensitivity and near blur. Also, they are not yet commercially available, so
      their use is limited and not practical. Further information is required for other
      methods of myopia control, such as the use of corneal reshaping contact lenses or
      bifocal soft contact lenses (BSCLs) with a distance center are promising, but
      currently no published randomized clinical trials exist.

PMID- 22161390
TI  - Complementary and miscellaneous interventions for nocturnal enuresis in children.
AB  - BACKGROUND: Nocturnal enuresis (bedwetting) is a socially disruptive and
      stressful condition which affects around 15% to 20% of five year olds, and up to
      2% of young adults. OBJECTIVES: To assess the effects of complementary
      interventions and others such as surgery or diet on nocturnal enuresis in
      children, and to compare them with other interventions. SEARCH METHODS: We
      searched PubMed (1950 to June 2010), EMBASE (1980 to June 2010), the Traditional
      Chinese Medical Literature Analysis and Retrieval System (TCMLARS) (1984 to June
      2010), Chinese Biomedical Literature Database (CBM) (1975 to June 2010), China
      National Knowledge Infrastructure (CNKI) (1979 to June 2010), VIP database (1989
      to June 2010), and the reference lists of relevant articles, all last searched 26
      June 2010. No language restriction was used. SELECTION CRITERIA: All randomised
      or quasi-randomised trials of complementary and other miscellaneous interventions
      for nocturnal enuresis in children were included except those focused solely on
      daytime wetting. Comparison interventions could include no treatment, placebo or
      sham treatment, alarms, simple behavioural treatment, desmopressin, imipramine
      and miscellaneous other drugs and interventions. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently assessed the quality of the eligible trials, and
      extracted data. MAIN RESULTS: In 24 randomised controlled trials, 2334 children
      were studied, of whom 1283 received a complementary intervention. The quality of
      the trials was poor: 5 trials were quasi-randomised, 5 showed differences at
      baseline and 17 lacked follow up data.The outcome was better after hypnosis than
      imipramine in one trial (relative risk (RR) for failure or relapse after stopping
      treatment 0.42, 95% confidence interval (CI) 0.23 to 0.78). Psychotherapy
      appeared to be better in terms of fewer children failing or relapsing than both
      alarm (RR 0.28, 95% CI 0.09 to 0.85) and rewards (RR 0.29, 95%CI 0.09 to 0.90)
      but this depended on data from only one trial. Medicinal herbs had better results
      than desmopressin in one trial (RR for failure or relapse after stopping
      treatment 0.35, 95% CI 0.14 to 0.85). Acupuncture had better results than sham
      control acupuncture (RR for failure or relapse after stopping treatment 0.67, 95%
      CI 0.48 to 0.94) in a further trial. Active chiropractic adjustment had better
      results than sham adjustment (RR for failure to improve 0.76, 95% CI 0.60 to
      0.95). However, each of these findings came from small single trials, and must be
      verified in further trials. The findings for diet and faradization were
      unreliable, and there were no trials including homeopathy or surgery. AUTHORS'
      CONCLUSIONS: There was weak evidence to support the use of hypnosis,
      psychotherapy, acupuncture, chiropractic and medicinal herbs but it was provided
      in each case by single small trials, some of dubious methodological rigour.
      Robust randomised trials are required with efficacy, cost-effectiveness and
      adverse effects clearly reported.

PMID- 22161391
TI  - Interventions to reduce risky sexual behaviour for preventing HIV infection in
      workers in occupational settings.
AB  - BACKGROUND: The workplace provides an important avenue to prevent HIV.
      OBJECTIVES: To evaluate the effect of behavioral interventions for reducing HIV
      on high risk sexual behavior when delivered in an occupational setting. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE,
      EMBASE and PsycINFO up until March 2011 and CINAHL, LILACS, DARE, OSH Update, and
      EPPI database up until October 2010. SELECTION CRITERIA: Randomised control
      trials (RCTs) in occupational settings or among workers at high risk for HIV that
      measured HIV, sexual transmitted diseases (STD), Voluntary Counseling and Testing
      (VCT), or risky sexual behaviour. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected studies for inclusion, extracted data and assessed risk of
      bias. We pooled studies that were similar. MAIN RESULTS: We found 8 RCTs with
      11,164 participants but one study did not provide enough data. Studies compared
      VCT to no VCT and education to no intervention and to alternative education.VCT
      uptake increased to 51% when provided at the workplace compared to a voucher for
      VCT (RR=14.0 (95% CI 11.8 to16.7)). After VCT, self-reported STD decreased (RR =
      0.10 (95% CI 0.01 to 0.73)) but HIV incidence (RR=1.4 (95% CI 0.7 to 2.7)) and
      unprotected sex (RR=0.71 (0.48 to 1.06)) did not decrease significantly.
      .Education reduced STDs (RR = 0.68 (95%CI 0.48 to 0.96)), unprotected sex
      (Standardised Mean Difference (SMD)= -0.17 (95% CI -0.29 to -0.05), sex with a
      commercial sex worker (RR = 0.88 (95% CI 0.81 to 0.96) but not multiple sexual
      partners (Mean Difference (MD) = -0.22 (95% CI -0.52 to 0.08) nor use of alcohol
      before sex (MD = -0.01 (95% CI of -0.11 to 0.08). AUTHORS' CONCLUSIONS: Workplace
      interventions to prevent HIV are feasible. There is moderate quality evidence
      that VCT offered at the work site increases the uptake of testing. Even though
      this did no lower HIV-incidence, there was a decrease in self-reported sexual
      transmitted diseases and a decrease in risky sexual behaviour. There is low
      quality evidence that educational interventions decrease sexually transmitted
      diseases, unprotected sex and sex with commercial sex workers but not sex with
      multiple partners and the use of alcohol before sex.More and better randomised
      trials are needed directed at high risk groups such as truck drivers or workers
      in areas with a very high HIV prevalence such as Southern Africa. Risky sexual
      behaviour should be measured in a standardised way.

PMID- 22161392
TI  - Botulinum toxin injections for adults with overactive bladder syndrome.
AB  - BACKGROUND: Overactive bladder syndrome (OAB) is a common condition with a
      significant negative impact on quality of life characterised by urgency with or
      without urge incontinence, frequency and nocturia.  Intravesical botulinum toxin
      is being increasingly used to treat severe overactive bladder refractory to
      standard management.  An increasing body of literature is forming that supports
      this technique as effective, well tolerated, and safe.  This review is a
      substantial update of the 2007 review of the same title. OBJECTIVES: The
      objective was to compare intravesical botulinum toxin with other treatments for
      neurogenic and idiopathic overactive bladder in adults. The hypothesis to be
      addressed were whether intravesical injection of botulinum toxin was better than
      placebo or no treatment; pharmacological and other non-pharmacological
      interventions; whether higher doses of botulinum toxin were better than lower
      doses; whether botulinum toxin in combination with other treatments was better
      than other treatments alone; whether one formulation of botulinum toxin is better
      than another; and whether one injection technique was better than another. SEARCH
      METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register
      (searched 23 February 2010). The Register contains trials identified from
      MEDLINE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL),
      and handsearching of journals and conference proceedings. Additionally, all
      reference lists of selected trials and relevant review papers were searched. No
      limitations were placed on the searches. SELECTION CRITERIA: All randomised or
      quasi-randomised controlled trials of treatment for OAB in adults in which at
      least one management arm involved intravesical injection of botulinum toxin were
      included. Participants had either neurogenic OAB or idiopathic OAB with or
      without stress incontinence. Comparison interventions could include no
      intervention, placebo, lifestyle modification, bladder retraining,
      pharmacological treatments, surgery, bladder instillation techniques,
      neuromodulation, and different types, doses, and injection techniques of
      botulinum toxin. DATA COLLECTION AND ANALYSIS: Binary outcomes were presented as
      relative risk and continuous outcomes by mean differences. Little data could be
      synthesised across studies due to differing study designs and outcome measures.
      Where applicable standard deviations were calculated from P values according to
      the formula described in section 7.7.3.3 of the Cochrane Handbook of Systematic
      Reviews of Interventions. Data were tabulated where possible with results taken
      from trial reports where this was not possible. Where multiple publications were
      found, the reports were treated as a single source of data. MAIN RESULTS:
      Nineteen studies were identified that met the inclusion criteria.  Most patients
      in the studies had neurogenic OAB, but some included patients with idiopathic
      OAB.  All studies demonstrated superiority of botulinum toxin to placebo.  Lower
      doses of botulinum toxin (100 to 150 U) appeared to have beneficial effects, but
      larger doses (300 U) may have been more effective and longer lasting, but with
      more side effects.  Suburothelial injection had comparable efficacy to
      intradetrusor injection. The effect of botulinum toxin may last for a number of
      months and is dependent upon dose and type of toxin used. Patients receiving
      repeated doses do not seem to become refractory to botulinum toxin. Botulinum
      toxin appeared to have beneficial effects in OAB that quantitatively exceeded the
      effects of intravesical resiniferatoxin. Intravesical botulinum toxin appeared to
      be reasonably safe; however, one study was halted due to a perceived unacceptable
      rate of urinary retention.  AUTHORS' CONCLUSIONS: Intravesical botulinum toxin
      appears to be an effective therapy for refractory OAB symptoms, but as yet little
      controlled trial data exist on benefits and safety compared with other
      interventions, or with placebo. Further robust data are required on long term
      outcomes, safety, and optimal dose of botulinum toxin for OAB.

PMID- 22161393
TI  - Progestogen for treating threatened miscarriage.
AB  - BACKGROUND: Miscarriage is a common complication encountered during pregnancy.
      The role of progesterone in preparing the uterus for the implantation of the
      embryo and its role in maintaining the pregnancy have been known for a long time.
      Inadequate secretion of progesterone in early pregnancy has been linked to the
      aetiology of miscarriage and progesterone supplementation has been used as a
      treatment for threatened miscarriage to prevent spontaneous pregnancy loss.
      OBJECTIVES: To determine the efficacy and the safety of progestogens in the
      treatment of threatened miscarriage. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (30 September 2011) and
      bibliographies of all located articles for any additional studies. SELECTION
      CRITERIA: Randomised or quasi-randomised controlled trials that compare
      progestogen with placebo, no treatment or any other treatment given in an effort
      to treat threatened miscarriage. DATA COLLECTION AND ANALYSIS: At least two
      authors assessed the trials for inclusion in the review, assessed trial quality
      and extracted the data. Data were checked for accuracy. MAIN RESULTS: We included
      four studies (421 participants) in the meta-analysis. In three studies all the
      participants met the inclusion criteria and in the fourth study, we included only
      the subgroup of participants who met the inclusion criteria in the meta-analysis.
      There was evidence of a reduction in the rate of spontaneous miscarriage with the
      use of progestogens compared to placebo or no treatment (risk ratio (RR) 0.53;
      95% confidence interval (CI) 0.35 to 0.79). There was no increase in the rate of
      antepartum haemorrhage (RR 0.76; 95% CI 0.30 to 1.94), or pregnancy-induced
      hypertension (RR 1.00; 95% CI 0.54 to 1.88) for the mother. The rate of
      congenital abnormalities was no different between the newborns of the mothers who
      received progestogens and those who did not (RR 0.70; 95% CI 0.10 to 4.82).
      AUTHORS' CONCLUSIONS: The data from this review suggest that the use of
      progestogens is effective in the treatment of threatened miscarriage with no
      evidence of increased rates of pregnancy-induced hypertension or antepartum
      haemorrhage as harmful effects to the mother, nor increased occurrence of
      congenital abnormalities on the newborn. However, the analysis was limited by the
      small number and the poor methodological quality of eligible studies (four
      studies) and the small number of the participants (421), which limit the power of
      the meta-analysis and hence of this conclusion.

PMID- 22161394
TI  - Interferon alpha for chronic hepatitis D.
AB  - BACKGROUND: Hepatitis D virus is a small defective RNA virus that requires the
      presence of hepatitis B virus infection to infect a person. Hepatitis D is a
      difficult-to-treat infection. Several clinical trials have been published on the
      efficacy of interferon alpha for hepatitis D virus (HDV) infection. However,
      there are few randomised trials evaluating the effects of interferon alpha, and
      it is difficult to judge any benefit of this intervention from the individual
      trials. OBJECTIVES: To evaluate the beneficial and harmful effects of interferon
      alpha for patients with chronic hepatitis D. SEARCH METHODS: We identified
      relevant for the review randomised clinical trials by electronic searches in the
      Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE,
      and Science Citation Index Expanded until May 2011. We also checked the
      bibliographic references of identified randomised trials, textbooks, and review
      articles in order to find randomised trials not identified by the electronic
      searches. SELECTION CRITERIA: Randomised clinical trials evaluating interferon
      alpha versus placebo or no intervention for patients with chronic hepatitis D
      infection. DATA COLLECTION AND ANALYSIS: Two authors assessed the trials and
      extracted data on mortality, virologic, biochemical, and histological response as
      well as adverse events at end of treatment and six months or more after
      completing treatment. The analyses were performed using the intention-to-treat
      principle including all randomised participants irrespective of follow-up. Drop
      outs, withdrawals, and non-compliance were considered as treatment failures. Data
      were analysed with fixed- and random-effects models. Reported results were based
      on fixed-effect model except in cases where statistical significance varied
      between the two models. MAIN RESULTS: Six randomised trials fulfilled the
      inclusion criteria. Two hundred and one randomised participants (male = 174) were
      included. The risk of bias in all the included trials was high. Five trials
      compared interferon alpha with no treatment in the control group. One of these
      trials had two treatment arms with a higher dose and lower dose of interferon
      alpha and a no-treatment control group. We analysed both treatment regimens as a
      single group in a primary analysis and as separate groups in the subgroup
      analysis of different interferon dosages. The sixth trial compared only a higher
      dose of interferon alpha with a lower dose.Meta-analysis of five trials comparing
      interferon alpha with no-treatment control group included 169 participants. There
      were seven drop-outs in the treatment group and nine in the control group. One
      patient out of 92 (1.1%) died in the interferon alpha group compared with zero
      out of 77 (0.0%) in the no-intervention control group (risk ratio (RR)) 3.00; 95%
      confidence interval (CI) 0.14 to 66.5). Interferon alpha led to failure of end of
      treatment virological response in 62/92 (67.4%) of the patients compared with
      71/77 (92.2%) in the untreated controls (RR 0.76, 95% CI 0.66 to 0.87, P = 0.0001
      by fixed-effect model and RR 0.71, 95% CI 0.43 to 1.16, P = 0.17 by random
      effects model). Failure of normalisation of alanine aminotransferase (ALT) at the
      end of treatment was seen in 60/92 (65.2%) patients treated with interferon alpha
      versus 76/77 (98.7%) in the control group (RR 0.69, 95% CI 0.59 to 0.80, P <
      0.00001). Sustained virological response was not achieved in 76/92 (82.6%) of
      patients on interferon compared with 73/77 (94.8%) of controls (RR 0.89, 95% CI
      0.80 to 0.98, P = 0.02). Serum alanine aminotransferase was abnormal in 81/92
      (88.0%) treated with interferon alpha patients at six months post-treatment
      follow-up compared with 76/77 (98.7%) in controls (RR 0.92, 95% CI 0.84 to 0.99,
      P = 0.04). There was no significant histological improvement in 67/92 (72.8%)
      patients treated with interferon alpha compared with 65/77 (84.4%) in controls
      (RR 0.86, 95% CI 0.74 to 1.00, P = 0.06).Two trials comparing a higher dose of
      interferon alpha with the lower dose showed no significant difference in
      sustained virological response (76.7% compared with 90.0%) (RR 0.85, 95% CI 0.68
      to 1.07, P = 0.16). Adverse events such as flu-like symptoms, asthenia, weight
      loss, alopecia, thrombocytopenia, and leukopenia were reported in all these
      trials and the adverse events were related to interferon alpha. These were common
      and sometimes severe. One patient in the treatment group was reported to have
      died by suicide towards the end of the study period. AUTHORS' CONCLUSIONS:
      Interferon alpha does not seem to cure hepatitis D in most patients. The agent
      seems effective in suppressing viral and liver disease activity in some patients,
      but this improvement is not sustained in the majority of patients. We cannot
      exclude overestimation of benefits and underestimation of harms due to high risk
      of bias (systematic errors) and high risk play of chance (random errors).
      Therefore, more randomised trials with large sample sizes and less risk of bias
      are needed before interferon can be recommended or refuted.

PMID- 22161396
TI  - Extracorporeal shock wave lithotripsy (ESWL) versus ureteroscopic management for
      ureteric calculi.
AB  - BACKGROUND: Ureteral stones frequently cause renal colic, and if left untreated,
      can lead to obstructive uropathy. Extracorporeal shock wave lithotripsy (ESWL)
      and ureteroscopy, with or without intracorporeal lithotripsy, are the most common
      interventions used to treat ureteral stones. ESWL treatment is less invasive than
      ureteroscopy, but has some limitations such as a high retreatment rate, and is
      not available in all centres. Recent advances in ureteroscopy have increased
      success rates and reduced complication rates. OBJECTIVES: To examine evidence
      from randomised controlled trials (RCTs) on the outcomes of ESWL or ureteroscopy
      in the treatment of ureteric calculi. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL in The Cochrane Library Issue 2,
      2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL,
      Clinicaltrials.gov, Google Scholar, reference lists of articles and abstracts
      from conference proceedings, all without language restriction. SELECTION
      CRITERIA: RCTs that compared ESWL with ureteroscopic retrieval of ureteric stones
      were included in this review. Study participants were adults with ureteric stones
      requiring intervention. Published and unpublished sources were considered for
      inclusion. DATA COLLECTION AND ANALYSIS: Three authors independently assessed
      study quality, risk of bias, and extracted data. Statistical analyses were
      performed using the random-effects model. Results were expressed as risk ratios
      (RR) for dichotomous outcomes or mean differences (MD) for continuous data, both
      with 95% confidence intervals (CI). MAIN RESULTS: Seven RCTs (1205 patients) were
      included in the review. Stone-free rates were lower in patients who underwent
      ESWL (7 studies, 1205 participants: RR 0.84, 95% CI 0.73 to 0.96) but re
      treatment rates were lower in ureteroscopy patients (6 studies, 1049
      participants: RR 6.18, 95% CI 3.68 to 10.38. ESWL-treated patients had less need
      for auxiliary treatment (5 studies, 751 participants: RR 0.43, 95% CI 0.25 to
      0.74; fewer complications (7 studies, 1205 participants: RR 0.54, 95% CI 0.33 to
      0.88); and shorter length of hospital stay (2 studies, 198 participants: MD -2.55
      days, 95% CI -3.24 to -1.86).Three studies adequately described the randomisation
      sequence, three studies were unclear on how they randomised, while one study had
      a high risk of selection bias. All the studies had an unclear risk of performance
      bias and detection bias, while all had a low risk of attrition bias, reporting
      bias, or other sources of bias identified. AUTHORS' CONCLUSIONS: Compared with
      ESWL, ureteroscopic removal of ureteral stones achieves a greater stone-free
      state, but with a higher complication rate and longer hospital stay.

PMID- 22161395
TI  - Interventions for reducing anxiety in women undergoing colposcopy.
AB  - BACKGROUND: Prior to the development of cervical cancer abnormal cervical cells
      can be detected on a cervical smear. The usual practice following an abnormal
      cervical smear is to perform colposcopy. Colposcopy is the visualisation of the
      cervix using a binocular microscope. Women experience high levels of anxiety and
      negative emotional responses at all stages of cervical screening. High levels of
      anxiety before and during colposcopy can have adverse consequences, including
      pain and discomfort during the procedure and high loss to follow-up rates. This
      review evaluates interventions designed to reduce anxiety levels during
      colposcopic examination. OBJECTIVES: To compare the efficacy of various
      interventions aimed at reducing anxiety during colposcopic examination in women.
      SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials
      Register, Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3,
      2010, MEDLINE and EMBASE up to July 2010. 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) of interventions to reduce anxiety during colposcopic examination. DATA
      COLLECTION AND ANALYSIS: Two review authors independently abstracted data and
      assessed risk of bias. Mean differences for anxiety levels, knowledge scores,
      pain, patient satisfaction and psychosexual dysfunction in women who underwent
      colposcopy were pooled in a random effects meta-analyses. MAIN RESULTS: We found
      six trials that met our inclusion criteria. These trials assessed the
      effectiveness of different interventions for reducing anxiety in women undergoing
      colposcopy for the first time.All comparisons were restricted to single trial
      analyses or meta analysis of just two trials. There was evidence from a
      reasonably large trial (n = 220) that was at low risk of bias to suggest that
      music during colposcopy significantly reduced anxiety levels (MD = -4.80, 95% CI:
      -7.86 to -1.74) and pain experienced during the procedure (MD = -1.71, 95% CI: 
      2.37 to -1.05) compared to not listening to music. There was no statistically
      significant difference between anxiety levels prior to colposcopy in women
      receiving information leaflets versus no leaflets and information leaflets, video
      and counselling versus information leaflets and video with no counselling.
      However, knowledge scores were significantly higher and psychosexual dysfunction
      scores were significantly lower in women who received leaflets compared to those
      who did not so there was some sort of benefit to giving patients information
      leaflets. There is evidence for video colposcopy from a quasi randomised trial
      which assessed 81 women showing significant anxiety reduction. AUTHORS'
      CONCLUSIONS: Anxiety appears to be reduced by playing music during colposcopy.
      Although information leaflets did not reduce anxiety levels, they did increase
      knowledge levels and are therefore useful in obtaining clinical consent to the
      colposcopic procedure. Leaflets also contributed to improved patient quality of
      life by reducing psychosexual dysfunction.

PMID- 22161397
TI  - Behavioral interventions to reduce the transmission of HIV infection among sex
      workers and their clients in high-income countries.
AB  - BACKGROUND: Interventions to change behaviour among sex workers and their clients
      have been identified as a strategy to reduce HIV transmission. However, there has
      been no systematic review that has examined and summarized their effects.
      OBJECTIVES: To identify and evaluate the effects of the studies performed on
      behavioural interventions to reduce the transmission of HIV infection among sex
      workers and their clients in high-income countries. SEARCH METHODS: Electronic
      searches were undertaken using MEDLINE, EMBASE, Cochrane Central Register of
      Controlled Trials (CENTRAL) and other databases between January 1980 and July
      2010. Experts in the field were contacted to locate any other studies. SELECTION
      CRITERIA: Randomised controlled trials or specified quasi-experimental designs
      with comparison groups that examined the effects of behavioural interventions
      aimed at reducing the risk of HIV or sexually transmitted infections (STIs)
      transmission among sex workers in high-income countries. We reviewed studies for
      outcome relevance and methodological rigor. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently applied the inclusion criteria to potential studies, and
      any disagreements were resolved by discussion. Studies were assessed for
      completeness of reporting and extracted data. MAIN RESULTS: A total of four
      studies were included, comprising two randomised controlled trials and two quasi
      experimental pretest-posttest trials with control groups involving 1795
      participants. No trials reported HIV prevalence/incidence as outcomes.Overall,
      the effects of behavioural interventions for sex workers in high-income countries
      on STI incidence did not differ significantly among two studies using a random
      effects model (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.11 to 1.98).
      Only one study found that the self-reported STI prevalence in clients of female
      sex workers was statistically significant (RR 0.09, 95%CI 0.01 to 0.72, P=0.02).
      There was no significant difference after behavioural intervention for condom
      use. Two studies demonstrated the effectiveness of intervention for knowledge of
      HIV transmission among sex workers (RR 1.82, 95%CI 1.55 to 2.14) and clients of
      sex workers (RR 1.93, 95%CI 1.46 to 2.55). AUTHORS' CONCLUSIONS: There is limited
      evidence from randomised controlled trials for the effectiveness of behavioural
      interventions to reduce the transmission of HIV infection among sex workers and
      their clients in high-income countries. Further randomised controlled trials are
      very likely to have important impacts on our confidence in the estimates of the
      effects, and are likely to change the estimates for effective interventions with
      outcomes of HIV incidence or prevalence and a variety of different settings among
      sex workers and their clients in high-income countries. Randomised controlled
      trials that test for the identification of effective interventions for HIV
      prevention with outcomes of biological endpoints, such as HIV incidence or
      prevalence, are needed for these neglected populations. More research is also
      needed for male or transgender sex workers and their clients in high-income
      countries.

PMID- 22161398
TI  - Methods of milk expression for lactating women.
AB  - BACKGROUND: This is an update of a 2008 Cochrane review. Breastfeeding is
      important. However, not all infants can feed at the breast and methods of
      expressing milk need evaluation. OBJECTIVES: To assess acceptability,
      effectiveness, safety, effect on composition, contamination and cost implications
      of methods of milk expression. SEARCH METHODS: We searched the Cochrane Pregnancy
      and Childbirth Group's Trials Register (20 January 2011), CINAHL (1982 to January
      2011), conference proceedings, secondary references and contacted researchers.
      SELECTION CRITERIA: Randomised and quasi-randomised trials comparing methods at
      any time after birth, and crossover trials commencing at least 28 days after
      birth. DATA COLLECTION AND ANALYSIS: Three authors independently assessed trials,
      extracted data and assessed risk of bias. Data were checked for accuracy. MAIN
      RESULTS: We included 23 studies with 10 studies (632 mothers) providing data for
      analysis.Mothers provided with a relaxation tape produced more milk than mothers
      who were not (mean difference (MD) 34.70 ml/single expression, 95% confidence
      interval (CI) 9.51 to 59.89, P = 0.007). A lower milk volume over six days was
      reported when comparing hand expression to the electric pump (standardised mean
      difference (SMD) -1.00 ml, 95% CI -1.64 to -0.36, P = 0.002); other studies of
      the same pump using different measures did not find a significant difference (12
      to 36 hours postpartum SMD -0.38 cc, 95% CI -0.86 to 0.10, P = 0.12); day five
      postpartum SMD -0.62 ml/day, 95% CI -1.43 to 0.19, P = 0.13). No evidence of
      difference in volume was found with simultaneous or sequential pumping, or
      between manual and electric pumps studied. One study reported a higher sodium
      concentration in hand expressed milk compared to a manual pump (SMD 0.59 mmol/L,
      95% CI 0.22 to 0.96, P = 0.002) and to an electric pump (SMD 0.70 mmol/L, 95% CI
      0.32 to 1.09, P = 0.0003), and lower potassium concentration compared to a manual
      pump (MD -0.37 mmol/L, 95% CI 0.00 to 0.73, P = 0.05) or to an electric pump (SMD
      -0.32 mmol/L, 95% CI -0.69 to 0.06, P = 0.10). No evidence of difference was
      found for energy content, milk contamination or adverse effects. Reports of
      maternal views were not comparable. Economic aspects were not reported.  
      AUTHORS' CONCLUSIONS: The most suitable method for milk expression may depend on
      the time since birth, purpose of expression and the individual mother and infant.
      Low cost interventions including early initiation when not feeding at the breast,
      relaxation, hand expression and lower cost pumps may be as effective, or more
      effective, than large electric pumps for some outcomes. Small sample sizes, large
      standard deviations, small number of studies reviewed, and the diversity of the
      interventions argue caution in applying these results beyond the specific method
      tested in the specific settings.

PMID- 22161399
TI  - Drug treatment for spinal muscular atrophy type I.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is caused by degeneration of anterior
      horn cells of the spinal cord, which leads to progressive muscle weakness.
      Children with SMA type I will never be able to sit without support and usually
      die by the age of two years. There are no known efficacious drug treatments that
      influence the course of the disease. This is an update of a review first
      published in 2009. OBJECTIVES: To evaluate whether drug treatment is able to slow
      or arrest the disease progression of SMA type I, and to assess if such therapy
      can be given safely. Drug treatment for SMA types II and III is the topic of a
      separate updated Cochrane review. SEARCH METHODS: We searched the Cochrane
      Neuromuscular Disease Group Specialized Register (8 March 2011), CENTRAL (The
      Cochrane Library 2011, Issue 1), MEDLINE (January 1991 to February 2011), EMBASE
      (January 1991 to February 2011) and ISI Web of Knowledge (January 1991 to 8 March
      2011). We searched the Clinical Trials Registry of the U.S. National Institute of
      Health (www.ClinicalTrials.gov) (8 March 2011) to identify additional trials that
      had not yet been published. SELECTION CRITERIA: We sought all randomised or quasi
      randomised trials that examined the efficacy of drug treatment for SMA type I.
      Participants had to fulfil the clinical criteria and have a deletion or mutation
      of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis.The primary outcome
      measure was time from birth until death or full time ventilation. Secondary
      outcome measures were development of rolling, sitting or standing within one year
      after the onset of treatment, and adverse events attributable to treatment during
      the trial period. DATA COLLECTION AND ANALYSIS: Two authors (RW and AV)
      independently reviewed and extracted data from all potentially relevant trials.
      For included studies, pooled relative risks and standardised mean differences
      were to be calculated to assess treatment efficacy. MAIN RESULTS: One small
      randomised controlled study comparing riluzole treatment to placebo for 10 SMA
      type 1 children was identified and included in the original review. No further
      trials were identified for the update in 2011. Regarding the primary outcome
      measure, three of seven children treated with riluzole were still alive at the
      ages of 30, 48 and 64 months, whereas all three children in the placebo group
      died; but the difference was not statistically significant. Regarding the
      secondary outcome measures, none of the children in the riluzole or placebo group
      developed the ability to roll, sit or stand, and no adverse effects were
      observed. For several reasons the overall quality of the study was low, mainly
      because the study was too small to detect an effect and because of baseline
      differences. Follow-up of the 10 included children was complete. AUTHORS'
      CONCLUSIONS: No drug treatment for SMA type I has been proven to have significant
      efficacy.

PMID- 22161400
TI  - Drug treatment for spinal muscular atrophy types II and III.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is caused by degeneration of anterior
      horn cells, which leads to progressive muscle weakness. Children with SMA type II
      do not develop the ability to walk without support and have a shortened life
      expectancy, whereas children with SMA type III develop the ability to walk and
      have a normal life expectancy. There are no known efficacious drug treatments
      that influence the disease course of SMA. This is an update of a review first
      published in 2009. OBJECTIVES: To evaluate whether drug treatment is able to slow
      or arrest the disease progression of SMA types II and III and to assess if such
      therapy can be given safely. Drug treatment for SMA type I is the topic of a
      separate updated Cochrane review. SEARCH METHODS: We searched the Cochrane
      Neuromuscular Disease Group Specialized Register (8 March 2011), Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1),
      MEDLINE (January 1991 to February 2011), EMBASE (January 1991 to February 2011)
      and ISI Web of Knowledge (January 1991 to March 8 2011). We also searched
      clinicaltrials.gov to identify as yet unpublished trials (8 March 2011).
      SELECTION CRITERIA: We sought all randomised or quasi-randomised trials that
      examined the efficacy of drug treatment for SMA types II and III. Participants
      had to fulfil the clinical criteria and have a deletion or mutation of the
      survival motor neuron 1 (SMN1) gene (5q11.2-13.2) that was confirmed by genetic
      analysis.The primary outcome measure was to be change in disability score within
      one year after the onset of treatment. Secondary outcome measures within one year
      after the onset of treatment were to be change in muscle strength, ability to
      stand or walk, change in quality of life, time from the start of treatment until
      death or full time ventilation and adverse events attributable to treatment
      during the trial period. DATA COLLECTION AND ANALYSIS: Two authors independently
      reviewed and extracted data from all potentially relevant trials. Pooled relative
      risks and pooled standardised mean differences were to be calculated to assess
      treatment efficacy. Risk of bias was systematically analysed. MAIN RESULTS: Six
      randomised placebo-controlled trials on treatment for SMA types II and III were
      found and included in the review: the four in the original review and two trials
      added in this update. The treatments were creatine (55 participants),
      phenylbutyrate (107 participants), gabapentin (84 participants), thyrotropin
      releasing hormone (9 participants), hydroxyurea (57 participants), and
      combination therapy with valproate and acetyl-L-carnitine (61 participants). None
      of these studies were completely free of bias. All studies had adequate blinding,
      sequence generation and reports of primary outcomes.None of the included trials
      showed any statistically significant effects on the outcome measures in
      participants with SMA types II and III. One participant died due to suffocation
      in the hydroxyurea trial and one participant died in the creatine trial. No
      participants in any of the other four trials died or reached the state of full
      time ventilation. Serious side effects were infrequent. AUTHORS' CONCLUSIONS:
      There is no proven efficacious drug treatment for SMA types II and III.

PMID- 22161401
TI  - Physical therapy for Bell's palsy (idiopathic facial paralysis).
AB  - BACKGROUND: Bell's palsy (idiopathic facial paralysis) is commonly treated by
      various physical therapy strategies and devices, but there are many questions
      about their efficacy. OBJECTIVES: To evaluate physical therapies for Bell's palsy
      (idiopathic facial palsy). SEARCH METHODS: We searched the Cochrane Database of
      Systematic Reviews and the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 1, 2011), MEDLINE (January 1966 to February 2011), EMBASE
      (January 1946 to February 2011), LILACS (January 1982 to February 2011), PEDro
      (from 1929 to February 2011), and CINAHL (January 1982 to February 2011). We
      included searches in clinical trials register databases until February 2011.
      SELECTION CRITERIA: We selected randomised or quasi-randomised controlled trials
      involving any physical therapy. We included participants of any age with a
      diagnosis of Bell's palsy and all degrees of severity. The outcome measures were:
      incomplete recovery six months after randomisation, motor synkinesis, crocodile
      tears or facial spasm six months after onset, incomplete recovery after one year
      and adverse effects attributable to the intervention. DATA COLLECTION AND
      ANALYSIS: Two authors independently scrutinised titles and abstracts identified
      from the search results. Two authors independently carried out risk of bias
      assessments, which , took into account secure methods of randomisation,
      allocation concealment, observer blinding, patient blinding, incomplete outcome
      data, selective outcome reporting and other bias. Two authors independently
      extracted data using a specially constructed data extraction form. We undertook
      separate subgroup analyses of participants with more and less severe disability.
      MAIN RESULTS: For this update to the original review, the search identified 65
      potentially relevant articles. Twelve studies met the inclusion criteria (872
      participants). Four trials studied the efficacy of electrical stimulation (313
      participants), three trials studied exercises (199 participants), and five
      studies compared or combined some form of physical therapy with acupuncture (360
      participants). For most outcomes we were unable to perform meta-analysis because
      the interventions and outcomes were not comparable.For the primary outcome of
      incomplete recovery after six months, electrostimulation produced no benefit over
      placebo (moderate quality evidence from one study with 86 participants). Low
      quality comparisons of electrostimulation with prednisolone (an active
      treatment)(149 participants), or the addition of electrostimulation to hot packs,
      massage and facial exercises (22 participants), reported no significant
      differences. Similarly a meta-analysis from two studies, one of three months and
      the other of six months duration, (142 participants) found no statistically
      significant difference in synkinesis, a complication of Bell's palsy, between
      participants receiving electrostimulation and controls. A single low quality
      study (56 participants), which reported at three months, found worse functional
      recovery with electrostimulation (mean difference (MD) 12.00 points (scale of 0
      to 100) 95% confidence interval (CI) 1.26 to 22.74).Two trials of facial
      exercises, both at high risk of bias, found no difference in incomplete recovery
      at six months when exercises were compared to waiting list controls or
      conventional therapy. There is evidence from a single small study (34
      participants) of moderate quality that exercises are beneficial on measures of
      facial disability to people with chronic facial palsy when compared with controls
      (MD 20.40 points (scale of 0 to 100), 95% CI 8.76 to 32.04) and from another
      single low quality study with 145 people with acute cases treated for three
      months where significantly fewer participants developed facial motor synkinesis
      after exercise (risk ratio 0.24, 95% CI 0.08 to 0.69). The same study showed
      statistically significant reduction in time for complete recovery, mainly in more
      severe cases (47 participants, MD -2.10 weeks, 95% CI -3.15 to -1.05) but this
      was not a prespecified outcome in this meta analysis.Acupuncture studies did not
      provide useful data as all were short and at high risk of bias. None of the
      studies included adverse events as an outcome. AUTHORS' CONCLUSIONS: There is no
      high quality evidence to support significant benefit or harm from any physical
      therapy for idiopathic facial paralysis. There is low quality evidence that
      tailored facial exercises can help to improve facial function, mainly for people
      with moderate paralysis and chronic cases. There is low quality evidence that
      facial exercise reduces sequelae in acute cases. The suggested effects of
      tailored facial exercises need to be confirmed with good quality randomised
      controlled trials.

PMID- 22161402
TI  - Infection control strategies for preventing the transmission of meticillin
      resistant Staphylococcus aureus (MRSA) in nursing homes for older people.
AB  - BACKGROUND: Nursing homes for older people provide an environment likely to
      promote the acquisition and spread of meticillin-resistant Staphylococcus aureus
      (MRSA), putting residents at increased risk of colonisation and infection. It is
      recognised that infection prevention and control strategies are important in
      preventing and controlling MRSA transmission. OBJECTIVES: To determine the
      effects of infection prevention and control strategies for preventing the
      transmission of MRSA in nursing homes for older people. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library 2011, Issue 2), the Cochrane Wounds Group Specialised Register
      (searched May 27th, 2011). We also searched Ovid MEDLINE (from 1950 to April Week
      2 2011), OVID MEDLINE (In-process and Other Non-Indexed Citations, April 26th
      2011) Ovid EMBASE (1980 to 2011 Week 16), EBSCO CINAHL (1982 to April 21st 2011),
      DARE (1992 to 2011, week 16), Web of Science (1981 to May 2011), and the Health
      Technology Assessment (HTA) website (1988 to May 2011). Research in progress was
      sought through Current Clinical Trials (www.controlled-trials.com), Medical
      Research Council Research portfolio, and HSRPRoj (current USA projects).
      SELECTION CRITERIA: All randomised and controlled clinical trials, controlled
      before and after studies and interrupted time series studies of infection
      prevention and control interventions in nursing homes for older people were
      eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors
      independently reviewed the results of the searches. Another review author
      appraised identified papers and undertook data extraction which was checked by a
      second review author. MAIN RESULTS: For this second update only one study was
      identified, therefore it was not possible to undertake a meta-analysis. A cluster
      randomised controlled trial in 32 nursing homes evaluated the effect of an
      infection control education and training programme on MRSA prevalence. The
      primary outcome was MRSA prevalence in residents and staff, and a change in
      infection control audit scores which measured adherence to infection control
      standards. At the end of the 12 month study, there was no change in MRSA
      prevalence between intervention and control sites, while mean infection control
      audit scores were significantly higher in the intervention homes compared with
      control homes. AUTHORS' CONCLUSIONS: There is a lack of research evaluating the
      effects on MRSA transmission of infection prevention and control strategies in
      nursing homes. Rigorous studies should be conducted in nursing homes, to test
      interventions that have been specifically designed for this unique environment.

PMID- 22161403
TI  - Pharmacologic interventions for treating phantom limb pain.
AB  - BACKGROUND: Phantom limb pain (PLP) is pain that arises in the missing limb after
      amputation and can be severe, intractable and disabling. Various medications have
      been studied in the treatment of phantom pain. Presently there is uncertainty in
      the optimal pharmacologic management of PLP.  OBJECTIVES: This review aims to
      summarize the evidence of effectiveness of pharmacologic interventions in
      treating PLP. SEARCH METHODS: We searched the Cochrane Pain, Palliative and
      Supportive Care Review Group (PaPaS) Trials Register, the Cochrane Controlled
      Trials Register (CENTRAL, The Cochrane Library), MEDLINE and EMBASE up to
      September 2011 for randomised and quasi-randomised trials comparing pharmacologic
      treatment with placebo, another active treatment, or no treatment. SELECTION
      CRITERIA: We included randomised and quasi-randomised trials studying the
      effectiveness of pharmacologic interventions in patients with established PLP.
      The outcomes considered were change in pain intensity, function, mood, sleep,
      quality of life, satisfaction and adverse effects. DATA COLLECTION AND ANALYSIS:
      Three review authors independently assessed the methodologic quality of the
      studies and extracted the data. We reported continuous and dichotomous data on
      change in pain intensity, function, mood/depression scores, sleep, quality of
      life, satisfaction for each study, where available. Because of the wide
      variability in the studies, we did not perform a meta-analysis for all the
      interventions and outcomes but we attempted to pool the results of some studies
      where possible. We prepared a qualitative description and narrative summary of
      results and described adverse effects. We assessed clinical heterogeneity by
      making qualitative comparisons in terms of the populations, interventions,
      outcomes/outcome measures and methods. MAIN RESULTS: From 583
      references/publications, we selected 13 studies involving 255 participants. Six
      groups of medications were reviewed, namely, N-methyl D-aspartate (NMDA) receptor
      antagonists, antidepressants, anticonvulsants, anaesthetics, opioids, and
      calcitonin. Ten studies were of high quality and three were of moderate quality
      based on both Jadad and Van Tulder criteria. Because of the wide variation
      (heterogeneity) in the pharmacologic interventions, outcome measures, analyses,
      reporting of results, duration of follow-ups and study designs, it was not
      possible to pool the results for most of the interventions and outcomes. Morphine
      (oral and intravenous) was effective in decreasing pain intensity in the short
      term with reported adverse effects being constipation, sedation, tiredness,
      dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory
      problems. The NMDA receptor antagonists, ketamine and dextromethorphan but not
      memantine, had analgesic effects. The adverse effects of ketamine were more
      serious and included loss of consciousness, sedation, hallucinations, hearing and
      position impairment, and insobriety. The results for gabapentin in terms of pain
      relief were conflicting but combining the results showed a trend towards benefit.
      Gabapentin, however, did not improve function, depression score and sleep
      quality. Side effects experienced were somnolence, dizziness, headache and
      nausea. Amitryptiline was not effective in PLP with dry mouth and dizziness as
      side effects based on one study. The findings for calcitonin and anaesthetics
      were variable. Adverse effects of calcitonin were headache, vertigo, drowsiness,
      nausea, vomiting, and hot and cold flushes. Most of the studies were limited by
      their small sample sizes. AUTHORS' CONCLUSIONS: The short- and long-term
      effectiveness of opioids, NMDA receptor antagonists, anticonvulsants,
      antidepressants, calcitonins, and anaesthetics for clinically relevant outcomes
      that include pain, function, mood, sleep, quality of life, satisfaction and
      adverse effects remains unclear. Morphine, gabapentin and ketamine demonstrate
      trends towards short-term analgesic efficacy. Memantine and amitriptyline were
      ineffective for PLP. Results, however, are to be interpreted with caution as
      these were based mostly on a small number of studies with limited sample sizes
      that varied considerably and also lacked long-term efficacy and safety outcomes.
      The direction of efficacy of calcitonin, anaesthetics and dextromethorphan need
      further clarification. Larger and more rigorous randomised controlled trials are
      needed to make stronger recommendations about which medications would be useful
      for clinical practice.

PMID- 22161404
TI  - Early additional food and fluids for healthy breastfed full-term infants.
AB  - BACKGROUND: Widespread recommendations from health organisations encourage
      exclusive breastfeeding for six months. However the addition of other fluids or
      foods before six months is common practice in many countries and communities.
      This practice suggests perceived benefits of early supplementation or lack of
      awareness of the possible risks. OBJECTIVES: To assess the benefits and harms of
      supplementation for full-term healthy breastfed infants and to examine the timing
      and type of supplementation. SEARCH METHODS: We searched the Cochrane Pregnancy
      and Childbirth Group's Trials Register (1 March 2011) and reference lists of all
      relevant retrieved papers. SELECTION CRITERIA: Randomised or quasi-randomised
      controlled trials in infants under six months of age comparing exclusive
      breastfeeding versus breastfeeding with any additional food or fluids. DATA
      COLLECTION AND ANALYSIS: Two authors independently selected the trials; three
      extracted data and assessed risk of bias. MAIN RESULTS: We included six trials
      (814 infants). Two trials in the early days after birth that reported data did
      not indicate that giving additional fluids was beneficial. For duration of
      breastfeeding, there was a significant difference favouring exclusive
      breastfeeding up to and including week 20 (risk ratio (RR) 1.45, 95% confidence
      interval (CI) 1.05 to 1.99), indicating that supplements may contribute to
      reducing the duration.For infant morbidity (three trials), one newborn trial
      found a statistically, but not clinically, significant difference in temperature
      at 72 hours (MD 0.10 degrees, 95% CI 0.01 to 0.19), and that serum glucose levels
      were higher in glucose supplemented infants in the first 24 hours, though not at
      48 hours (MD -0.24mmol/l, 95% CI -0.51 to 0.03). Two trials with four- to six
      month-old infants did not indicate any benefit to supplemented infants to 26
      weeks nor any risks related to morbidity or weight change.None of the trials
      reported on the remaining primary outcomes, infant mortality or physiological
      jaundice. AUTHORS' CONCLUSIONS: We were unable to fully assess the benefits or
      harms of supplementation or to determine the impact from timing and type of
      supplementation .We found no benefit to newborn infants and possible negative
      effects on the duration of breastfeeding from the brief use of additional water
      or glucose water. For infants at four to six months, we found no benefit from
      additional foods nor any risks related to morbidity or weight change. Future
      studies should examine the longer term effects on infants and mothers, though
      randomising infants to receive supplements without medical need may be considered
      unethical.We found no evidence for disagreement with the recommendation of
      international health associations that exclusive breastfeeding should be
      recommended for healthy infants for the first six months.

PMID- 22161405
TI  - Mirtazapine versus other antidepressive agents for depression.
AB  - BACKGROUND: Mirtazapine has a unique mechanism of antidepressive action and is
      one of the commonly used antidepressants in clinical practice. OBJECTIVES: The
      aim of the present review was to assess the evidence on the efficacy and
      acceptability of mirtazapine compared with other antidepressive agents in the
      acute-phase treatment of major depression in adults. SEARCH METHODS: We searched
      the Cochrane Collaboration Depression, Anxiety and Neurosis review group's
      specialised register (CCDANCTR), which includes relevant randomised controlled
      trials from the following bibliographic databases: The Cochrane Library (all
      years to April 2011), EMBASE, (1980 to July 2011) MEDLINE (1950 to July 2011) and
      PsycINFO (1974 to July 2011). Reference lists of the reports of relevant studies
      were checked and experts in the field contacted. The review was not limited to
      English-language articles. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) allocating participants with major depression to mirtazapine versus any
      other antidepressive agent. DATA COLLECTION AND ANALYSIS: Two authors
      independently checked eligibility and extracted data on an intention-to-treat
      basis. The primary outcome was response to treatment. The secondary outcomes
      included dropouts and individual adverse events.Meta-analyses were conducted
      using the random-effects model. MAIN RESULTS: A total of 29 RCTs (n = 4974),
      mostly following up the participants for six weeks in outpatient clinics and
      inadequately reporting the risk of bias, were included. In comparison with
      tricyclic antidepressants (10 trials, n = 1553) there was no robust evidence to
      detect a difference between mirtazapine and tricyclics in terms of response at
      two weeks (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.64 to 1.13) or at
      the end of acute-phase treatment (at 6 to 12 weeks) (OR 0.89, 95% CI 0.72 to
      1.10). In comparison with selective serotonin reuptake inhibitors (SSRIs) (12
      trials, n = 2626) mirtazapine was significantly more effective at two weeks (OR
      1.57, 95% CI 1.30 to 1.88) and at the end of acute-phase treatment (OR 1.19, 95%
      CI 1.01 to 1.39). Mirtazapine was significantly more effective than a serotonin
      noradrenaline reuptake inhibitor (venlafaxine only, two trials, n = 415) at two
      weeks (OR 2.29, 95% CI 1.45 to 3.59) and at the end of acute-phase treatment (OR
      1.53, 95% CI 1.03 to 2.25).In terms of dropouts, there was no robust evidence to
      detect a difference between mirtazapine and other antidepressants. Mirtazapine
      was more likely to cause weight gain or increased appetite and somnolence than
      SSRIs but less likely to cause nausea or vomiting and sexual dysfunction.
      AUTHORS' CONCLUSIONS: Some statistically significant and possibly clinically
      meaningful differences between mirtazapine and other antidepressive agents were
      found for the acute-phase treatment of major depression. Mirtazapine is likely to
      have a faster onset of action than SSRIs during the acute-phase treatment.
      Dropouts occur similarly in participants treated with mirtazapine and those
      treated with other antidepressants, although the adverse event profile of
      mirtazapine is unique.

PMID- 22161406
TI  - Planned caesarean section for women with a twin pregnancy.
AB  - BACKGROUND: Twin pregnancies are associated with increased perinatal mortality,
      mainly related to prematurity, but complications during birth may contribute to
      perinatal loss or morbidity. The option of planned caesarean section to avoid
      such complications must therefore be considered. On the other hand, randomised
      trials of other clinical interventions in the birth process to avoid problems
      related to labour and birth (planned caesarean section for breech, and continuous
      electronic fetal heart rate monitoring), have shown an unexpected discordance
      between short-term perinatal morbidity and long-term neurological outcome. The
      risks of caesarean section for the mother in the current and subsequent
      pregnancies must also be taken into account. OBJECTIVES: To determine the short-
      and long-term effects on mothers and their babies, of planned caesarean section
      for twin pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (30 September 2011). SELECTION CRITERIA:
      Randomised trials comparing a policy of caesarean section with planned vaginal
      birth for women with twin pregnancy. DATA COLLECTION AND ANALYSIS: Two
      researchers independently assessed eligibility, quality and extracted data. Data
      were checked for accuracy. MAIN RESULTS: One small trial with unconfirmed
      allocation concealment compared caesarean section with planned vaginal birth in
      60 women with vertex/non-vertex twin pregnancies. There were no differences in
      perinatal outcome. The trial was too small to exclude the possibility of
      clinically meaningful benefits of either approach. There is one additional trial
      currently ongoing. AUTHORS' CONCLUSIONS: There is a lack of robust evidence to
      guide clinical advice regarding the method of birth for twin pregnancies. Women
      should be informed of possible benefits and risks of either approach, including
      short-term and long-term consequences for both mother and babies. Future research
      should aim to provide unbiased evidence, including long-term outcomes.

PMID- 22161407
TI  - Perineal techniques during the second stage of labour for reducing perineal
      trauma.
AB  - BACKGROUND: Most vaginal births are associated with some form of trauma to the
      genital tract. The morbidity associated with perineal trauma is significant,
      especially when it comes to third- and fourth-degree tears. Different perineal
      techniques and interventions are being used to prevent perineal trauma. These
      interventions include perineal massage, warm compresses and perineal management
      techniques. OBJECTIVES: The objective of this review was to assess the effect of
      perineal techniques during the second stage of labour on the incidence of
      perineal trauma. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (20 May 2011), the Cochrane Central Register
      of ControlledTrials (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (January
      1966 to 20 May 2011) and CINAHL (January 1983 to 20 May 2011). SELECTION
      CRITERIA: Published and unpublished randomised and quasi-randomised controlled
      trials evaluating any described perineal techniques during the second stage. DATA
      COLLECTION AND ANALYSIS: Three review authors independently assessed trails for
      inclusion, extracted data and evaluated methodological quality. Data were checked
      for accuracy. MAIN RESULTS: We included eight trials involving 11,651 randomised
      women. There was a significant effect of warm compresses on reduction of third-
      and fourth-degree tears (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.28
      to 0.84 (two studies, 1525 women)). There was also a significant effect towards
      favouring massage versus hands off to reduce third- and fourth-degree tears (RR
      0.52, 95% CI 0.29 to 0.94 (two studies, 2147 women)). Hands off (or poised)
      versus hand on showed no effect on third- and fourth-degree tears, but we
      observed a significant effect of hands off on reduced rate of episiotomy (RR
      0.69, 95% CI 0.50 to 0.96 (two studies, 6547 women)). AUTHORS' CONCLUSIONS: The
      use of warm compresses on the perineum is associated with a decreased occurrence
      of perineal trauma. The procedure has shown to be acceptable to women and
      midwives. This procedure may therefore be offered to women.

PMID- 22161408
TI  - Framing of health information messages.
AB  - BACKGROUND: The same information about the evidence on health effects can be
      framed either in positive words or in negative words. Some research suggests that
      positive versus negative framing can lead to different decisions, a phenomenon
      described as the framing effect. Attribute framing is the positive versus
      negative description of a specific attribute of a single item or a state, for
      example, "the chance of survival with cancer is 2/3" versus "the chance of
      mortality with cancer is 1/3". Goal framing is the description of the
      consequences of performing or not performing an act as a gain versus a loss, for
      example, "if you undergo a screening test for cancer, your survival will be
      prolonged" versus "if you don't undergo screening test for cancer, your survival
      will be shortened". OBJECTIVES: To evaluate the effects of attribute (positive
      versus negative) framing and of goal (gain versus loss) framing of the same
      health information, on understanding, perception of effectiveness,
      persuasiveness, and behavior of health professionals, policy makers, and
      consumers. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, issue 3 2007), MEDLINE (Ovid)
      (1966 to October 2007), EMBASE (Ovid) (1980 to October 2007), PsycINFO (Ovid)
      (1887 to October 2007). There were no language restrictions. We reviewed the
      reference lists of related systematic reviews, included studies and of excluded
      but closely related studies. We also contacted experts in the field. SELECTION
      CRITERIA: We included randomized controlled trials, quasi-randomised controlled
      trials, and cross-over studies with health professionals, policy makers, and
      consumers evaluating one of the two types of framing. DATA COLLECTION AND
      ANALYSIS: Two review authors extracted data in duplicate and independently. We
      graded the quality of evidence for each outcome using the GRADE approach. We
      standardized the outcome effects using standardized mean difference (SMD). We
      stratified the analysis by the type of framing (attribute, goal) and conducted
      pre-planned subgroup analyses based on the type of message (screening,
      prevention, and treatment). The primary outcome was behaviour. We did not assess
      any adverse outcomes. MAIN RESULTS: We included 35 studies involving 16,342
      participants (all health consumers) and reporting 51 comparisons.In the context
      of attribute framing, participants in one included study understood the message
      better when it was framed negatively than when it was framed positively (1 study;
      SMD -0.58 (95% confidence interval (CI) -0.94 to -0.22); moderate effect size;
      low quality evidence). Although positively-framed messages may have led to more
      positive perception of effectiveness than negatively-framed messages (2 studies;
      SMD 0.36 (95% CI -0.13 to 0.85); small effect size; low quality evidence), there
      was little or no difference in persuasiveness (11 studies; SMD 0.07 (95% CI -0.23
      to 0.37); low quality evidence) and behavior (1 study; SMD 0.09 (95% CI -0.14 to
      0.31); moderate quality evidence).In the context of goal framing, loss messages
      led to a more positive perception of effectiveness compared to gain messages for
      screening messages (5 studies; SMD -0.30 (95% CI -0.49 to -0.10); small effect
      size; moderate quality evidence) and may have been more persuasive for treatment
      messages (3 studies; SMD -0.50 (95% CI -1.04 to 0.04); moderate effect size; very
      low quality evidence). There was little or no difference in behavior (16 studies;
      SMD -0.06 (95% CI -0.15 to 0.03); low quality evidence). No study assessed the
      effect on understanding. AUTHORS' CONCLUSIONS: Contrary to commonly held beliefs,
      the available low to moderate quality evidence suggests that both attribute and
      goal framing may have little if any consistent effect on health consumers'
      behaviour. The unexplained heterogeneity between studies suggests the possibility
      of a framing effect under specific conditions. Future research needs to
      investigate these conditions.

PMID- 22161409
TI  - Inhaled corticosteroids versus long-acting beta(2)-agonists for chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Long-acting beta(2)-agonists and inhaled corticosteroids can be used
      as maintenance therapy by patients with moderate to severe chronic obstructive
      pulmonary disease. These interventions are often taken together in a combination
      inhaler. However, the relative added value of the two individual components is
      unclear. OBJECTIVES: To determine the relative effects of inhaled corticosteroids
      (ICS) compared to long-acting beta(2)-agonists (LABA) on clinical outcomes in
      patients with stable chronic obstructive pulmonary disease. SEARCH METHODS: We
      searched the Cochrane Airways Group Specialised Register of trials (latest search
      August 2011) and reference lists of articles. SELECTION CRITERIA: We included
      randomised controlled trials comparing inhaled corticosteroids and long-acting
      beta(2)-agonists in the treatment of patients with stable chronic obstructive
      pulmonary disease. DATA COLLECTION AND ANALYSIS: Three authors independently
      assessed trials for inclusion and then extracted data on trial quality, study
      outcomes and adverse events. We also contacted study authors for additional
      information. MAIN RESULTS: We identified seven randomised trials (5997
      participants) of good quality with a duration of six months to three years. All
      of the trials compared ICS/LABA combination inhalers with LABA and ICS as
      individual components. Four of these trials included fluticasone and salmeterol
      monocomponents and the remaining three included budesonide and formoterol
      monocomponents. There was no statistically significant difference in our primary
      outcome, the number of patients experiencing exacerbations (odds ratio (OR) 1.22;
      95% CI 0.89 to 1.67), or the rate of exacerbations per patient year (rate ratio
      (RR) 0.96; 95% CI 0.89 to 1.02) between inhaled corticosteroids and long-acting
      beta(2)-agonists. The incidence of pneumonia, our co-primary outcome, was
      significantly higher among patients on inhaled corticosteroids than on long
      acting beta(2)-agonists whether classified as an adverse event (OR 1.38; 95% CI
      1.10 to 1.73) or serious adverse event (Peto OR 1.48; 95% CI 1.13 to 1.93).
      Results of the secondary outcomes analysis were as follows. Mortality was higher
      in patients on inhaled corticosteroids compared to patients on long-acting
      beta(2)-agonists (Peto OR 1.17; 95% CI 0.97 to 1.42), although the difference was
      not statistically significant. Patients treated with beta(2)-agonists showed
      greater improvements in pre-bronchodilator FEV(1) compared to those treated with
      inhaled corticosteroids (mean difference (MD) 18.99 mL; 95% CI 0.52 to 37.46),
      whilst greater improvements in health-related quality of life were observed in
      patients receiving inhaled corticosteroids compared to those receiving long
      acting beta(2)-agonists (St George's Respiratory Questionnaire (SGRQ) MD -0.74;
      95% CI -1.42 to -0.06). In both cases the differences were statistically
      significant but rather small in magnitude. There were no statistically
      significant differences between ICS and LABA in the number of hospitalisations
      due to exacerbations, number of mild exacerbations, peak expiratory flow,
      dyspnoea, symptoms scores, use of rescue medication, adverse events, all cause
      hospitalisations, or withdrawals from studies. AUTHORS' CONCLUSIONS: Placebo
      controlled trials have established the benefits of both long-acting beta-agonist
      and inhaled corticosteroid therapy for COPD patients as individual therapies.
      This review, which included trials allowing comparisons between LABA and ICS, has
      shown that the two therapies confer similar benefits across the majority of
      outcomes, including the frequency of exacerbations and mortality. Use of long
      acting beta-agonists appears to confer a small additional benefit in terms of
      improvements in lung function compared to inhaled corticosteroids. On the other
      hand, inhaled corticosteroid therapy shows a small advantage over long-acting
      beta-agonist therapy in terms of health-related quality of life, but inhaled
      corticosteroids also increase the risk of pneumonia. This review supports current
      guidelines advocating long-acting beta-agonists as frontline therapy for COPD,
      with regular inhaled corticosteroid therapy as an adjunct in patients
      experiencing frequent exacerbations.

PMID- 22161410
TI  - Edaravone for acute ischaemic stroke.
AB  - BACKGROUND: Neuroprotection is a promising therapeutic strategy for the treatment
      of acute ischaemic stroke. Edaravone is a neuroprotective agent that has been
      widely used in China, and several studies have suggested that it may be
      beneficial in acute ischaemic stroke. OBJECTIVES: To assess the efficacy and
      safety of edaravone for acute ischaemic stroke. SEARCH METHODS: We searched the
      Cochrane Stroke Group Trials Register (November 2010) and the Chinese Stroke
      Trials Register (November 2010). In addition, we searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4),
      MEDLINE (1950 to November 2010), EMBASE (1980 to November 2010), China National
      Knowledge Infrastructure (1979 to November 2010), Chinese Biomedical Database
      (1979 to November 2010), Chinese Evidence-Based Medicine Database (November 2010)
      and Chinese Science and Technology Journals Database (1980 to November 2010). In
      an attempt to identify further published, unpublished and ongoing trials we
      searched reference lists and clinical trials and research registers, and
      contacted a pharmaceutical company, researchers and study authors. SELECTION
      CRITERIA: We included randomised controlled trials comparing edaravone with
      placebo or no intervention in patients with acute ischaemic stroke. DATA
      COLLECTION AND ANALYSIS: Two review authors selected trials for inclusion,
      assessed trial quality and independently extracted the data. MAIN RESULTS: We
      included three trials, involving 496 participants, and defined four trials as
      waiting assessment. All three included trials were of edaravone plus another
      treatment compared with the other treatment alone. The dose of edaravone
      injections in the three trials was the same at 60 mg per day. The course of
      treatment in all three trials is 14 days. None of the included trials reported
      the pre-specified primary outcome of death or dependency defined using the
      modified Rankin scale during the follow-up period. The three trials evaluated the
      effect of edaravone at different times and using different methods. All three
      trials reported adverse events; there were no differences between the treatment
      group and the control group. Overall, edaravone appeared to increase the
      proportion of participants with marked neurological improvement compared with the
      control group, and the difference was significant (risk ratio (RR) 1.99, 95%
      confidence interval (CI) 1.60 to 2.49). AUTHORS' CONCLUSIONS: The risk of bias in
      the included trials was moderate and the sample was small. Hence, although the
      data in this review show an effective treatment trend of edaravone for acute
      ischaemic stroke, further large, high-quality trials are required to confirm this
      trend.

PMID- 22161411
TI  - Adjuvant radiotherapy following radical prostatectomy for prostate cancer.
AB  - BACKGROUND: Men who have a radical prostatectomy (RP) for prostate cancer that
      does not involve lymph nodes, but extends beyond the prostate capsule into the
      seminal vesicles or to surgical margins, are at increased risk of relapse. In men
      with these high risk factors, radiotherapy (RT) directed at the prostate bed
      after surgery may reduce this risk, and be curative. OBJECTIVES: To evaluate the
      effect of adjuvant RT following RP for prostate cancer in men with high risk
      features compared with RP. SEARCH METHODS: We searched the Cochrane Prostatic
      Diseases and Urological Cancers Specialised Register (23 February 2011), the
      Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE (January 1966 to
      February 2011), PDQ(r) (Physician Data Query) trial registry databases for
      ongoing studies (2 November 2010), reference lists from selected studies and
      reviews, and handsearched relevant conference proceedings. SELECTION CRITERIA:
      Randomised controlled trials (RCT) comparing RP followed by RT with RP alone.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for
      inclusion and bias and extracted data for analysis. Authors were contacted to
      clarify data and obtain missing information. MAIN RESULTS: We found three RCTs
      involving 1815 men. Adjuvant RT following prostatectomy did not affect overall
      survival at 5 years (RD (risk difference) 0.00; 95% CI -0.03 to 0.03), but
      improved survival at 10 years (RD -0.11; 95% CI -0.20 to -0.02). Adjuvant RT did
      not improve prostate cancer-specific mortality at 5 years (RD -0.01; 95% CI -0.03
      to 0.00). Adjuvant RT did not reduce metastatic disease at 5 years (RD -0.00; 95%
      CI -0.04 to 0.03), but reduced it at 10 years (RD -0.11; 95% CI -0.20 to -0.01).
      It improved local control at 5 and 10 years (RD -0.10; 95% CI -0.13 to -0.06 and
      RD -0.14; 95% CI -0.21 to -0.07, respectively), and biochemical progression-free
      survival at 5 years and 10 years (RD -0.16; 95% CI -0.21 to -0.11 and RD -0.29;
      95% CI -0.39 to -0.19, respectively). There were no data for clinical disease
      free survival. Adjuvant RT increased acute and late gastrointestinal toxicity [do
      you have the rd for this?], urinary stricture (RD 0.05; 95% CI 0.01 to 0.09) and
      incontinence (RD 0.04; 95% CI 0.01 to 0.08). It did not increase erectile
      dysfunction or degrade quality of life (RD 0.01; 95% CI -0.06 to -0.26), but with
      limited data. AUTHORS' CONCLUSIONS: Adjuvant RT after RP improves overall
      survival and reduces the rate of distant metastases, but these effects are only
      evident with longer follow up. At 5 and 10 years it improves local control and
      reduces the risk of biochemical failure, although the latter is not a clinical
      endpoint. Moderate or severe acute and late toxicity is minimal. There is an
      increased risk of urinary stricture and incontinence, but no detriment to quality
      of life, based on limited data. Given that the majority of men who have undergone
      a RP have a longer life expectancy, radiotherapy should be considered for those
      with high-risk features following radical prostatectomy. The optimal timing is
      unclear.

PMID- 22161412
TI  - Probiotics for maintenance of remission in ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis is a chronic relapsing disease characterised by
      diffuse mucosal inflammation limited to the colon. Current maintenance treatments
      have multiple adverse events and an effective treatment with minimal adverse
      events is desired. Several studies have demonstrated the importance of intestinal
      flora in the pathogenesis of ulcerative colitis. It has been suggested that
      modifying the bacterial flora with probiotics may attenuate the inflammatory
      process and prevent relapses in ulcerative colitis. OBJECTIVES: The primary
      objectives were to determine the efficacy and safety of probiotics for the
      maintenance of remission in ulcerative colitis. SEARCH METHODS: The Cochrane
      Central Register of Controlled Tials (CENTRAL), MEDLINE (1966 to July 2011),
      EMBASE (1974 to July 2011), CINAHL (1982 to July 2011) and the Cochrane
      Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialised Trial
      Register were searched. Manufacturers of probiotics were contacted to identify
      any unpublished trials. References of trials were also searched for any
      additional trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) that
      compared probiotics against placebo or any other intervention for the maintenance
      of remission in ulcerative colitis were eligible for inclusion. DATA COLLECTION
      AND ANALYSIS: Data extraction and assessment of methodological quality of
      included studies were independently performed by two authors. The main outcome
      measure was the occurrence of clinical or endoscopic relapse. MAIN RESULTS: Four
      studies (n = 587) met the inclusion criteria and were included in the review.
      Three trials compared probiotics to mesalazine and one trial compared probiotics
      with placebo. The studies ranged in length from 3 to 12 months. The risk of bias
      was high in two studies due to incomplete outcome data and lack of blinding. The
      methods used for allocation concealment were unclear for all four studies. There
      was no statistically significant difference between probiotics and mesalazine for
      maintenance of remission in UC. Relapse was reported in 40.1% of patients in the
      probiotics group compared to 34.1% of patients in the mesalazine group (3
      studies; 555 patients: OR 1.33; 95% CI 0.94 to 1.90 ; I(2) = 11%). There was no
      statistically significant difference in the incidence of adverse events. Twenty
      six per cent of patients in the probiotics group experienced at least one adverse
      event compared to 24% of patients in the mesalazine group (2 studies; 430
      patients OR 1.21; 95% CI 0.80 to 1.84; I(2) =27%). Adverse events reported in the
      mesalazine-controlled studies include diarrhea, mucous secretion, bloody stools,
      abdominal pain, flatulence and distension, nausea and vomiting and headache. A
      small placebo controlled trial (n = 32) found no statistically significant
      difference in efficacy. Seventy-five per cent of probiotic patients relapsed at
      one year compared to 92% of placebo patients (OR 0.27; 95% CI 0.03 to 2.68).
      Adverse events reported in the placebo-controlled study include flatulence,
      abdominal bloating and pain, changes in faecal consistency, arthralgia,
      sacroiliitis, tiredness, incontinence, stress, oral blisters, eye dryness,
      headache, dizziness, influenza, gastroenteritis, cystitis and pneumonia. AUTHORS'
      CONCLUSIONS: Given the relatively small number of patients in the pooled
      analysis, the small number of events and the high risk and unclear risk of bias
      in the included studies, there is insufficient evidence to make conclusions about
      the efficacy of probiotics for maintenance of remission in UC. There is a lack of
      well-designed RCTs in this area and further research is needed.

PMID- 22161413
TI  - Nitric oxide donors for cervical ripening in first-trimester surgical abortion.
AB  - BACKGROUND: Cervical priming before first-trimester surgical abortion is
      recommended in certain groups of women. Nitric oxide (NO) donors induce cervical
      ripening without uterine contractions, but the efficacy and side effects are of
      concern. OBJECTIVES: To evaluate efficacy, side effects and complications of NO
      donors for cervical ripening before first-trimester surgical abortion. SEARCH
      METHODS: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE and
      POPLINE. We also searched reference lists of retrieved papers. We contacted
      experts in the field for information on both published and unpublished trials.
      SELECTION CRITERIA: Randomised controlled trials comparing NO donors alone or in
      combination with other methods for cervical ripening in first-trimester surgical
      abortion. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected and
      extracted the data onto a data extraction form. We processed the data using
      Review Manager (RevMan5) software. MAIN RESULTS: We included nine studies
      involving 766 participants. There were no serious complications (infection
      requiring antibiotic treatment, blood transfusion, complications requiring
      unintended operation, cervical injury, uterine perforation, death or serious
      morbidity) in the trials included.NO donors were more effective in cervical
      ripening comparing with placebo or no treatment. Baseline cervical dilatation
      before the procedure was higher in NO donors group (mean difference 0.30, 95% CI
      0.01, 0.58) The cumulative force required to dilate the cervix to 8 mm (mean
      difference -4.29, 95% CI -9.92, 1.35), headache (RR 1.73, 95% CI 0.86, 3.46),
      abdominal pain (RR 0.87, 95% CI 0.50, 1.50) or patient satisfaction (RR 0.95, 95%
      CI 0.84, 1.07) were not different. More nausea and vomiting occurred in the women
      who received a NO donor (RR 2.62, 95% CI 1.07, 6.45).NO donors were inferior to
      prostaglandins for cervical ripening. The cumulative force required to dilate the
      cervix to 8-9 mm was higher (mean difference 13.12, 95% CI 9.72, 16.52) and
      baseline cervical dilatation was less (mean difference -0.73, 95% CI -1.01, 
      0.45) in the NO donor group. Side effects including headache (RR 5.13, 95% CI
      3.29, 8.00), palpitation (RR 3.43, 95% CI 1.64, 7.15), dizziness (RR 3.29, 95% CI
      1.46, 7.41) and intraoperative blood loss (mean difference 33.59 ml, 95% CI
      24.50, 42.67) were also higher. However, abdominal pain (RR 0.33, 95% CI 0.25,
      0.44) and vaginal bleeding (RR 0.14, 95% CI 0.07, 0.27) was less in the NO donor
      group. Patient satisfaction was not different.One trial compared a NO donor with
      a NO donor plus prostaglandin. The cumulative force required to dilate the cervix
      to 8 mm was higher (mean difference 14.50, 95% CI 0.50, 28.50) in the NO donor
      group. There was no difference in headache (RR 0.88, 95% CI 0.38, 2.00),
      abdominal pain (RR 0.14, 95% CI 0.02, 1.07) or intraoperative blood loss (mean
      difference -50, 95% CI -164.19, 64.19). AUTHORS' CONCLUSIONS: NO donors are
      superior to placebo or no treatment, but inferior to prostaglandins for first
      trimester cervical ripening, and associated with more side effects.

PMID- 22161414
TI  - Fluoride supplements (tablets, drops, lozenges or chewing gums) for preventing
      dental caries in children.
AB  - BACKGROUND: Dietary fluoride supplements were first introduced to provide
      systemic fluoride in areas where water fluoridation is not available. Since 1990,
      the use of fluoride supplements in caries prevention has been re-evaluated in
      several countries. OBJECTIVES: To evaluate the efficacy of fluoride supplements
      for preventing dental caries in children. SEARCH METHODS: We searched the
      Cochrane Oral Health Group's Trials Register (to 12 October 2011), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue
      3), MEDLINE via OVID (1950 to 12 October 2011), EMBASE via OVID (1980 to 12
      October 2011), WHOLIS/PAHO/MEDCARIB/LILACS/BBO via BIREME (1982 to 12 October
      2011), and Current Controlled Trials (to 12 October 2011). We handsearched
      reference lists of articles and contacted selected authors. SELECTION CRITERIA:
      We included randomised or quasi-randomised controlled trials comparing, with
      minimum follow-up of 2 years, fluoride supplements (tablets, drops, lozenges)
      with no fluoride supplement or with other preventive measures such as topical
      fluorides in children less than 16 years of age at the start. The main outcome
      was caries increment measured by the change in decayed, missing and filled tooth
      surfaces (DMFS). DATA COLLECTION AND ANALYSIS: Two review authors, independently
      and in duplicate, assessed the eligibility of studies for inclusion, and carried
      out risk of bias assessment and data extraction. In the event of disagreement, we
      sought consensus and consulted a third review author. We contacted trial authors
      for missing information. We used the prevented fraction (PF) as a metric for
      evaluating the efficacy of the intervention. The PF is defined as the mean caries
      increment in controls minus mean caries increment in the treated group divided by
      mean caries increment in controls. We conducted random-effects meta-analyses when
      data could be pooled. We assessed heterogeneity in the results of the studies by
      examining forest plots and by using formal tests for homogeneity. We recorded
      adverse effects (fluorosis) when the studies provided relevant data. MAIN
      RESULTS: We included 11 studies in the review involving 7196 children.In
      permanent teeth, when fluoride supplements were compared with no fluoride
      supplement (three studies), the use of fluoride supplements was associated with a
      24% (95% confidence interval (CI) 16 to 33%) reduction in decayed, missing and
      filled surfaces (D(M)FS). The effect of fluoride supplements was unclear on
      deciduous or primary teeth. In one study, no caries-inhibiting effect was
      observed on deciduous teeth while in another study, the use of fluoride
      supplements was associated with a substantial reduction in caries increment.When
      fluoride supplements were compared with topical fluorides or with other
      preventive measures, there was no differential effect on permanent or deciduous
      teeth.The review found limited information on the adverse effects associated with
      the use of fluoride supplements. AUTHORS' CONCLUSIONS: This review suggests that
      the use of fluoride supplements is associated with a reduction in caries
      increment when compared with no fluoride supplement in permanent teeth. The
      effect of fluoride supplements was unclear on deciduous teeth. When compared with
      the administration of topical fluorides, no differential effect was observed. We
      rated 10 trials as being at unclear risk of bias and one at high risk of bias,
      and therefore the trials provide weak evidence about the efficacy of fluoride
      supplements.

PMID- 22161415
TI  - Surgical orbital decompression for thyroid eye disease.
AB  - BACKGROUND: Orbital decompression is an established procedure for the management
      of exophthalmos and visual rehabilitation from optic neuropathy in cases of
      thyroid eye disease. Numerous procedures for removal of orbital bony wall, fat or
      a combination of these for a variety of indications in different stages of the
      disease have been well reported in the medical literature. However, the relative
      effectiveness and safety of these procedures in relation to the various
      indications remains unclear. OBJECTIVES: To review current published evidence for
      the effectiveness of surgical orbital decompression for disfiguring proptosis in
      adult thyroid eye disease and summa rise information on possible complications
      and the quality of life from the studies identified. SEARCH METHODS: We searched
      CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The
      Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to October 2011), EMBASE
      (January 1980 to October 2011), the metaRegister of Controlled Trials (mRCT)
      (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov).
      There were no date or language restrictions in the electronic searches for
      trials. The electronic databases were last searched on 6 October 2011. We
      searched oculoplastic textbooks, conference proceedings from the European and
      American Society of Ophthalmic Plastic and Reconstructive Surgery (ESOPRS,
      ASOPRS), European Ophthalmological Society (SOE), the Association for Research in
      Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) for
      the years 2000 to 2009 to identify relevant data. We attempted to contact
      researchers who are active in this field for information about further published
      or unpublished studies. SELECTION CRITERIA: We included randomised controlled
      trials (RCTs) with no restriction on date or language comparing two or more
      surgical methods for orbital decompression with removal of bony wall, orbital fat
      or a combination of both for disfiguring proptosis or comparison of surgical
      techniques with any form of medical decompression. DATA COLLECTION AND ANALYSIS:
      Each review author independently assessed study abstracts identified from the
      electronic and manual searches. Author analysis was then compared and full papers
      for appropriate studies were obtained according to the inclusion criteria.
      Disagreements between the authors were resolved by discussion. MAIN RESULTS: We
      identified two randomised trials eligible for inclusion in the review. There was
      significant variability between the trials for interventions, methodology and
      outcome measures and therefore meta-analysis was not performed. One study
      suggested that the transantral approach and endoscopic transnasal technique had
      similar effects in reducing exophthalmos but that the endoscopic approach may be
      safer, relating to fewer complications. This study had short-term follow-up and
      lacked information on our primary outcome (success or failure of treatment). The
      second study provided evidence that intravenous steroids may be superior to
      primary surgical decompression in the management of compressive optic neuropathy
      requiring less secondary surgical procedures, although it relates more frequently
      to transient side effects. This study was weakened by a small sample size. Until
      more credible evidence is available recommendations as to best treatment cannot
      be reliably made. AUTHORS' CONCLUSIONS: A single study showed that the
      transantral approach for orbital decompression was related to more complications
      than the endoscopic transnasal technique which is preferred by Ear, Nose and
      Throat (ENT) surgeons, usually as an adjunctive procedure. Intravenous steroids
      were reported in a single trial to be the most efficient intervention for
      dysthyroid optic neuropathy. The majority of published literature on orbital
      decompression for thyroid eye disease consists of retrospective, cohort, or case
      series studies. Although these provide useful descriptive information,
      clarification is required to show the relative effectiveness of each intervention
      for various indications.The two RCTs reviewed are not robust enough to provide
      credible evidence to our understanding of current decompressive surgery and to
      support recommendations for clinical practice. There is evidence from currently
      available uncontrolled studies that removal of the medial and lateral wall
      (balanced decompression) with or without fat removal may be the most effective
      surgical method related to only a few complications.There is a clear need for
      randomised studies evaluating the balanced two-wall, three-wall and orbital fat
      decompression techniques. Comparison with other surgical techniques for orbital
      decompression or with immunosuppression in cases of compressive optic neuropathy
      would also be important. These studies should primarily address the reduction of
      exophthalmos, disease severity, complication rates, quality of life and cost of
      the intervention.

PMID- 22161416
TI  - Physical training for McArdle disease.
AB  - BACKGROUND: McArdle disease is a rare metabolic myopathy caused by a complete
      absence of the enzyme muscle glycogen phosphorylase. Affected people experience
      symptoms of fatigue and cramping within minutes of exercise and are at risk for
      acute muscle injury (rhabdomyolysis) and acute renal failure. If the first few
      minutes of exercise are paced, a 'second wind' will occur enabling exercise to
      continue. This is due to mobilisation and utilisation of alternative fuel
      substrates. Aerobic training appears to improve work capacity by increasing
      cardiovascular fitness. OBJECTIVES: To assess the effects of aerobic training in
      people with McArdle disease. SEARCH METHODS: We searched the Cochrane
      Neuromuscular Disease Group Specialized Register (11 January 2011), CENTRAL
      (2010, Issue 4), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980
      to January 2011). SELECTION CRITERIA: All randomised and quasi-randomised
      controlled studies of aerobic exercise training in people of all ages with
      McArdle disease. DATA COLLECTION AND ANALYSIS: Two authors identified possible
      studies for inclusion and assessed their methodological quality. Had more than
      one study of sufficient methodological quality been identified we would have
      undertaken a meta-analysis. MAIN RESULTS: There were no randomised or quasi
      randomised controlled trials of aerobic training in people with McArdle disease.
      However, three open studies using small numbers of participants provided some
      evidence that aerobic training improves fitness without adverse events in people
      with McArdle disease. AUTHORS' CONCLUSIONS: Evidence from non-randomised studies
      using small numbers of patients suggest that it would be safe and worthwhile for
      larger controlled trials of aerobic training to be undertaken in people with
      McArdle disease.

PMID- 22161417
TI  - Light-emitting diode phototherapy for unconjugated hyperbilirubinaemia in
      neonates.
AB  - BACKGROUND: Phototherapy is the mainstay of treatment of neonatal
      hyperbilirubinaemia. The commonly used light sources for providing phototherapy
      are special blue fluorescent tubes, compact fluorescent tubes and halogen
      spotlights. However, light emitting diodes (LEDs) as light sources with high
      luminous intensity, narrow wavelength band and higher delivered irradiance could
      make phototherapy more efficacious than the conventional phototherapy units.
      OBJECTIVES: To evaluate the effect of LED phototherapy as compared to
      conventional phototherapy in decreasing serum total bilirubin levels and duration
      of treatment in neonates with unconjugated hyperbilirubinaemia. SEARCH METHODS:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library 2010, Issue 1), MEDLINE (1966 to April 30, 2010) and EMBASE
      (1988 to July 8, 2009). Handsearches of the proceedings of annual meetings of The
      European Society for Paediatric Research and The Society for Pediatric Research
      were conducted through 2010. SELECTION CRITERIA: Randomised or quasi-randomised
      controlled trials were eligible for inclusion if they enrolled neonates (term and
      preterm) with unconjugated hyperbilirubinaemia and compared LED phototherapy with
      other light sources (fluorescent  tubes, compact fluorescent tubes, halogen
      spotlight; method of administration: conventional or fibreoptic). DATA COLLECTION
      AND ANALYSIS: We used the standard methods of The Cochrane Collaboration and its
      Neonatal Review Group for data collection and analysis. MAIN RESULTS: Six
      randomised controlled trials met the inclusion criteria for this review. Four
      studies compared LED and halogen light sources. Two studies compared LED and
      compact fluorescent light sources. The duration of phototherapy (six studies, 630
      neonates) was comparable in LED and non-LED phototherapy groups (mean difference
      (hours) -0.43, 95% CI -1.91 to 1.05). The rate of decline of serum total
      bilirubin (STB) (four studies, 511 neonates) was also similar in the two groups
      (mean difference (mg/dL/hour) 0.01, 95% CI -0.02 to 0.04). Treatment failure,
      defined as the need of additional phototherapy or exchange blood transfusion (1
      study, 272 neonates), was comparable (RR 1.83, 95% CI 0.47 to 7.17). Side effects
      of phototherapy such as hypothermia (RR 6.41, 95% CI 0.33 to 122.97),
      hyperthermia (RR 0.61, 95% CI 0.18 to 2.11) and skin rash (RR 1.83, 95% CI 0.17
      to 19.96) were rare and occurred with similar frequency in the two groups.
      AUTHORS' CONCLUSIONS: LED light source phototherapy is efficacious in bringing
      down levels of serum total bilirubin at rates that are similar to phototherapy
      with conventional (compact fluorescent lamp (CFL) or halogen) light sources.
      Further studies are warranted for evaluating efficacy of LED phototherapy in
      neonates with haemolytic jaundice or in the presence of severe
      hyperbilirubinaemia (STB >= 20 mg/dL).

PMID- 22161418
TI  - Systemic corticosteroids for acute sinusitis.
AB  - BACKGROUND: Acute sinusitis is a common reason for patients to seek primary care
      consultations. The related impairment of daily functioning and quality of life is
      attributable to symptoms such as facial pain and nasal congestion. OBJECTIVES: To
      assess the effectiveness of systemic corticosteroids in relieving symptoms of
      acute sinusitis. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) Issue 2, 2011, which includes the Acute Respiratory
      Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects
      (DARE) and the NHS Health Economics Database, MEDLINE (1966 to June week 2, 2011)
      and EMBASE (January 2009 to June 2011). SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing systemic corticosteroids to placebo or standard clinical
      care for patients with acute sinusitis. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed methodological quality of the trials and extracted
      data. MAIN RESULTS: Four RCTs with a total of 1008 adult participants met our
      inclusion criteria. We judged studies to be of moderate methodological quality.
      Acute sinusitis was defined clinically in all trials. However, the three trials
      performed in ear, nose and throat (ENT) outpatient clinics also used radiological
      assessment as part of their inclusion criteria. All participants received oral
      antibiotics and were assigned to either oral corticosteroids (prednisone 24 mg to
      80 mg daily or betamethasone 1 mg daily) or the control treatment (placebo in
      three trials and non-steroidal anti-inflammatory drugs (NSAIDs) in one trial). In
      all trials, participants treated with oral corticosteroids were more likely to
      have short-term resolution or improvement of symptoms than those receiving the
      control treatment: at Days 3 to 7, risk ratio (RR) 1.4, 95% CI 1.1 to 1.8; risk
      difference (RD) 20% (6% to 34%) and at Days 4 to 10 or 12, RR 1.3, 95% CI (1.0 to
      1.7), RD 18% (3% to 33%). An analysis of the three trials with placebo as a
      control treatment showed similar results but with a lesser effect size: Days 3 to
      6: RR 1.2, 95% CI (1.1 to 1.4), RD 12% (5% to 19%) and Days 4 to 10 or 12: RR
      1.1, 95% CI (1.0 to 1.2), RD 10% (3% to 16%). Scenario analysis showed that
      outcomes missing from the trial reports might have introduced attrition bias (a
      worst-case scenario showed no statistically significant beneficial effect of oral
      corticosteroids). We did not identify any data on the long-term effects of oral
      corticosteroids on this condition, such as effects on relapse or recurrence
      rates. Reported side effects of oral corticosteroids were limited and mild.
      AUTHORS' CONCLUSIONS: Current evidence suggests that oral corticosteroids as an
      adjunctive therapy to oral antibiotics are effective for short-term relief of
      symptoms in acute sinusitis. However, data are limited and there is a significant
      risk of bias. High quality trials assessing the efficacy of systemic
      corticosteroids both as an adjuvant and a monotherapy in primary care patients
      with acute sinusitis should be initiated.

PMID- 22161419
TI  - Home-based child development interventions for preschool children from socially
      disadvantaged families.
AB  - BACKGROUND: Social disadvantage can have a significant impact on early child
      development, health and wellbeing. What happens during this critical period is
      important for all aspects of development. Caregiving competence and the quality
      of the environment play an important role in supporting development in young
      children and parents have an important role to play in optimising child
      development and mitigating the negative effects of social disadvantage. Home
      based child development programmes aim to optimise children's developmental
      outcomes through educating, training and supporting parents in their own home to
      provide a more nurturing and stimulating environment for their child. OBJECTIVES:
      To determine the effects of home-based programmes aimed specifically at improving
      developmental outcomes for preschool children from socially disadvantaged
      families. SEARCH METHODS: We searched the following databases between 7 October
      and 12 October 2010: Cochrane Central Register of Controlled Trials (CENTRAL)
      (2010, Issue 4), MEDLINE (1950 to week 4, September 2010), EMBASE (1980 to Week
      39, 2010), CINAHL (1937 to current), PsycINFO (1887 to current), ERIC (1966 to
      current), ASSIA (1987 to current), Sociological Abstracts (1952 to current),
      Social Science Citation Index (1970 to current). We also searched reference lists
      of articles. SELECTION CRITERIA: Randomised controlled trials comparing home
      based preschool child development interventions with a 'standard care' control.
      Participants were parents with children up to the age of school entry who were
      socially disadvantaged in respect of poverty, lone parenthood or ethnic minority
      status. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies,
      assessed the trials' risk of bias and extracted data. MAIN RESULTS: We included
      seven studies, which involved 723 participants. We assessed four of the seven
      studies as being at high risk of bias and three had an unclear risk of bias; the
      quality of the evidence was difficult to assess as there was often insufficient
      detail reported to enable any conclusions to be drawn about the methodological
      rigour of the studies. Four trials involving 285 participants measured cognitive
      development and we synthesised these data in a meta-analysis. Compared to the
      control group, there was no statistically significant impact of the intervention
      on cognitive development (standardised mean difference (SMD) 0.30; 95% confidence
      interval -0.18 to 0.78). Only three studies reported socioemotional outcomes and
      there was insufficient data to combine into a meta-analysis. No study reported on
      adverse effects. AUTHORS' CONCLUSIONS: This review does not provide evidence of
      the effectiveness of home-based interventions that are specifically targeted at
      improving developmental outcomes for preschool children from socially
      disadvantaged families. Future studies should endeavour to better document and
      report their methodological processes.

PMID- 22161420
TI  - Coenzyme Q10 for Parkinson's disease.
AB  - BACKGROUND: A number of preclinical studies in both in vitro and in vivo models
      of Parkinson's disease have demonstrated that coenzyme Q10 can protect the
      nigrostriatal dopaminergic system. Some clinical trials have looked at the
      neuroprotective effects of coenzyme Q10 in patients with early and midstage
      Parkinson's disease. OBJECTIVES: To assess the evidence from randomized
      controlled trials on the efficacy and safety of treatment with coenzyme Q10
      compared to placebo in patients with early and midstage Parkinson's disease.
      SEARCH METHODS: We searched the Cochrane Movment Disorders Group Trials Register,
      CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (January 1966 to March
      2011), and EMBASE (January 1985 to March 2011). We handsearched the references
      quoted in the identified trials, congress reports from the most important
      neurological association and movement disorder societies in Europe and America
      (March 2011), checked reference lists of relevant studies and contacted other
      researchers. SELECTION CRITERIA: We included randomized controlled trials (RCTs)
      that compared coenzyme Q10 to placebo for patients who suffered early and
      midstage primary Parkinson's disease. Studies in which the method of
      randomization or concealment were unknown were included. Cross-over studies were
      excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      trial quality and extracted data. All disagreements were resolved by consensus
      between authors and were explained. We attempted to contact the authors of
      studies for further details if any data were missing and to establish the
      characteristics of unpublished trials through correspondence with the trial
      coordinator or principal investigator. Adverse effects information was collected
      from the trials. MAIN RESULTS: Four randomized, double-blind, placebo-controlled
      trials with a total of 452 patients met the inclusion criteria and were included
      in the review. In overall, there were improvements in activities of daily living
      (ADL) UPDRS (WMD -3.12, 95% CI -5.88 to -0.36) and Schwab and England (WMD 4.43,
      95% CI 0.05 to 8.81) for coenzyme Q10 at 1200 mg/d for 16 months versus
      placebo.In safety outcomes, only the risk ratios (RR) of pharyngitis (RR 1.04,
      95% CI 0.18 to 5.89) and diarrhea (RR 1.39, 95% CI 0.62 to 3.16) are mild
      elevated between coenzyme Q10 therapy and placebo and there were no differences
      in the number of withdrawals due to adverse effects (RR 0.61, 95% CI 0.23 to
      1.62). AUTHORS' CONCLUSIONS: Coenzyme Q10 therapy with 1200 mg/d for 16 months
      was well tolerated by patients with Parkinson's disease. The improvements in ADL
      UPDRS and Schwab and England were positive, but it need to be further confirmed
      by larger sample. For total and other subscores of UPDRS, the effects of coenzyme
      Q10 seemed to be less clear.

PMID- 22161421
TI  - Statins for primary prevention of venous thromboembolism.
AB  - BACKGROUND: Venous thromboembolism (VTE) is common in clinical practice. The
      efficacy of statins in the primary prevention of VTE remains unproven.
      OBJECTIVES: To assess the efficacy of statins in the primary prevention of VTE.
      SEARCH METHODS: The Cochrane Peripheral Vascular Diseases (PVD) Group searched
      their Specialised Register (last searched April 2011) and CENTRAL (2011, Issue
      2). The authors searched MEDLINE (January 1966 to March 2011); EMBASE (1974 to
      March 2011); ISI Web of Knowledge (2001 to March 2011); the Chinese Biomedical
      Literature Database (1978 to March 2011) and other resources (including clinical
      trials registers, reference lists and presentations at various conferences.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed statins
      were considered. The outcomes we evaluated were the rates of VTE, cardiovascular
      and cerebrovascular events, death and adverse events. Two authors independently
      selected RCTs against inclusion criteria. Disagreements were resolved by
      discussion with a third author. DATA COLLECTION AND ANALYSIS: Data extraction was
      independently carried out by two authors. Disagreements were resolved by
      discussion with a third author. Two authors independently assessed the risk of
      bias according to a standard quality checklist provided by the PVD Group. MAIN
      RESULTS: We included one RCT (17 citations) with 17,802 participants that
      assessed rosuvastatin for preventing VTE. Our analysis showed that rosuvastatin
      reduced the incidence of VTE (odds ratio (OR) 0.57, 95% confidence interval (CI)
      0.37 to 0.86) and deep vein thrombosis (DVT) (OR 0.45, 95% CI 0.25 to 0.79), the
      risk of any (fatal and non-fatal) myocardial infarction (MI) (OR 0.45, 95% CI
      0.30 to 0.69), any (fatal and non-fatal) stroke (OR 0.51, 95% CI 0.34 to 0.78),
      but did not reduce the incidence of pulmonary embolism (PE) (OR 0.77, 95% CI 0.41
      to 1.46) and death after VTE (OR 0.50, 95% CI 0.20 to 1.24). Rosuvastatin did not
      reduce the incidence of any serious adverse event (OR 0.95, 95% CI 0.90 to 1.06).
      AUTHORS' CONCLUSIONS: Available evidence showed that rosuvastatin was associated
      with a reduced incidence of VTE, but the evidence was limited to a single RCT.
      Randomised controlled trials of statins (including rosuvastatin) are needed to
      evaluate the efficacy of statins in the prevention of VTE.

PMID- 22161422
TI  - Social skills training for Attention Deficit Hyperactivity Disorder (ADHD) in
      children aged 5 to 18 years.
AB  - BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) in children is
      associated with hyperactivity and impulsitivity, attention problems, and
      difficulties with social interactions. Pharmacological treatment may alleviate
      symptoms of ADHD but seldom solves difficulties with social interactions. Social
      skills training may benefit ADHD children in their social interactions. We
      examined the effects of social skills training on children's social competences,
      general behaviour, ADHD symptoms, and performance in school. OBJECTIVES: To
      assess the effects of social skills training in children and adolescents with
      ADHD. SEARCH METHODS: We searched the following electronic databases: CENTRAL
      (2011, Issue1), MEDLINE (1948 to March 2011), EMBASE (1980 to March 2011), ERIC
      (1966 to March 2011 ), AMED (1985 to June 2011), PsycINFO (1806 to March 2011),
      CINAHL (1980 to March 2011), and Sociological Abstracts (1952 to March 2011). We
      also searched the metaRegister of Controlled Trials on 15 October 2010. We did
      not apply any language or date restrictions to the searches. We searched online
      conference abstracts and contacted 176 experts in the field for possible
      information about unpublished or ongoing RCTs. SELECTION CRITERIA: Randomised
      trials investigating social skills training for children with ADHD as a stand
      alone treatment or as an adjunct to pharmacological treatment. DATA COLLECTION
      AND ANALYSIS: We conducted the review according to the Cochrane Handbook for
      Systematic Reviews of Intervention. Two authors (OJS, MS) extracted data
      independently using an appropriate data collection form. We performed the
      analyses using Review Manager 5 software. MAIN RESULTS: We included 11 randomised
      trials described in 26 records (all full text articles) in the review. The trials
      included a total of 747 participants. All participants were between five and 12
      years of age. No trials assessed adolescents. In 10 of the trials the
      participants suffered from different comorbidities.The duration of the
      interventions ranged from eight to 10 weeks (eight trials) up to two years. The
      types of social skills interventions were named social skills training, cognitive
      behavioural intervention, multimodal behavioural/psychosocial therapy,
      behavioural therapy/treatment, behavioural and social skills treatment, and
      psychosocial treatment. The content of the social skills interventions were
      comparable and based on a cognitive behavioural model. Most of the trials
      compared child social skills training and parent training plus medication versus
      medication alone. Some of the experimental interventions also included teacher
      consultations.More than half of the trials were at high risk of bias regarding
      generation of the allocation sequence and allocation concealment. No trial
      reported blinding of participants and personnel and most of the trials had no
      reports regarding differences between groups in collateral medication for
      comorbid disorders. Overall, the trials had high risk of bias due to systematic
      errors. Even so, as recommended by the Cochrane Handbook of Systematic Reviews of
      Interventions, we used all eligible trials in the meta-analysis, but the results
      are downgraded to low quality evidence.There were no statistically significant
      treatment effects either on social skills competences (positive value = better
      for the intervention group) (SMD 0.16; 95% CI -0.04 to 0.36; 5 trials, n = 392),
      on the teacher-rated general behaviour (negative value = better for the
      intervention group) (SMD 0.00; 95% CI -0.21 to 0.21; 3 trials, n = 358), or on
      the ADHD symptoms (negative value = better for the intervention group) (SMD 
      0.02; 95% CI -0.19 to 0.16; 6 trials, n = 515).No serious or non-serious adverse
      events were reported. AUTHORS' CONCLUSIONS: The review suggests that there is
      little evidence to support or refute social skills training for adolescents with
      ADHD. There is need for more trials, with low risk of bias and with a sufficient
      number of participants, investigating the efficacy of social skills training
      versus no training for both children and adolescents.

PMID- 22161423
TI  - Face-down positioning or posturing after macular hole surgery.
AB  - BACKGROUND: Macular holes cause significant loss of central vision. With the aim
      of improving the outcome of surgery, a variable period of face-down positioning
      may be advised. OBJECTIVES: To evaluate the evidence of the impact of
      postoperative face-down positioning on the outcome of surgery for macular hole.
      SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision
      Group Trials Register) (The Cochrane Library 2011, Issue 8), MEDLINE (January
      1950 to August 2011), EMBASE (January 1980 to August 2011), the International
      Standard Randomised Controlled Trial Number Register (ISRCTN Register)
      (http://www.controlled-trials.com), the WHO International Clinical Trials
      Registry Platform (ICTRP) (http://www.who.int/ictrp/search/en) and
      ClinicalTrials.gov (http://clinicaltrials.gov). There were no date or language
      restrictions in the electronic searches for trials. The electronic databases were
      last searched on 29 August 2011. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) in which postoperative face-down positioning was
      compared to no face-down positioning following surgery for macular holes. DATA
      COLLECTION AND ANALYSIS: Data were collected and analysed independently by two
      authors. MAIN RESULTS: Three RCTs were identified, A, B and C; one of which was
      unpublished data. We were unable to conduct a meta-analysis due to study
      heterogeneity regarding duration of face-down positioning and surgical methods
      (use of inner limiting peel). All three studies suggested an overall beneficial
      effect of posturing in terms of closure of holes: (A: risk ratio (RR) 1.10; 95%
      confidence interval (CI) 1.00 to 1.20, P = 0.05); B: RR 1.58, CI 1.0 to 2.5, P =
      0.01; C: RR 1.03, CI 0.9 to 1.17, P = 0.67). For holes which were smaller than
      400 microns in size, all three studies reported that there was no significant
      effect of face-down positioning on successful hole closure (A: RR 1.03, CI 0.95
      to 1.12; B: RR 1.0, CI 0.68 to 1.46; C: RR 1.03, CI 0.9 to 1.17). However, for
      holes which were larger than 400 microns in size, both of the studies which
      examined macular holes of this size agreed on the effectiveness of face-down
      positioning on hole closure following surgery (A: RR 1.2, CI 1.01 to 1.42, P =
      0.04; B: RR 2.27, CI 1.04 to 4.97, P = 0.04). AUTHORS' CONCLUSIONS: There is
      currently insufficient evidence from which to draw firm conclusions about the
      impact of postoperative face-down positioning on the outcome of surgery for
      macular hole. Of three RCTs, two suggested a benefit in larger holes but none
      demonstrated evidence of a benefit in smaller holes.CONSORT adherent RCTs and
      large scale, well designed non-randomised observational studies are needed to
      determine with confidence the value of this intervention.

PMID- 22161424
TI  - Topical interventions for genital lichen sclerosus.
AB  - BACKGROUND: Lichen sclerosus is a chronic, inflammatory skin condition that most
      commonly occurs in adult women, although it may also be seen in men and children.
      It primarily affects the genital area and around the anus, where it causes
      persistent itching and soreness. Scarring after inflammation may lead to severe
      damage by fusion of the vulval lips (labia); narrowing of the vaginal opening;
      and burying of the clitoris in women and girls, as well as tightening of the
      foreskin in men and boys, if treatments are not started early. Affected people
      have an increased risk of genital cancers. OBJECTIVES: To assess the effects of
      topical interventions for genital lichen sclerosus and adverse effects reported
      in included trials. SEARCH METHODS: We searched the following databases up to 16
      September 2011: the Cochrane Skin Group Specialised Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE
      (from 2005), EMBASE (from 2007), LILACS (from 1982), CINAHL (from 1981), British
      Nursing Index and Archive (from 1985), Science Citation Index Expanded (from
      1945), BIOSIS Previews (from 1926), Conference Papers Index (from 1982), and
      Conference Proceedings Citation Index - Science (from 1990). We also searched
      ongoing trial registries and scanned the bibliographies of included studies,
      published reviews, and papers that had cited the included studies. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) of topical interventions in genital
      lichen sclerosus. DATA COLLECTION AND ANALYSIS: Two authors independently
      selected trials, extracted data, and assessed the risk of bias. A third author
      was available for resolving differences of opinion. MAIN RESULTS: We included 7
      RCTs, with a total of 249 participants, covering 6 treatments. Six of these RCTs
      tested the efficacy of one active intervention against placebo or another active
      intervention, while the other trial tested three active interventions against
      placebo.When compared to placebo in one trial, clobetasol propionate 0.05% was
      effective in treating genital lichen sclerosus in relation to the following
      outcomes: 'participant-rated improvement or remission of symptoms' (risk ratio
      (RR) 2.85, 95% confidence interval (CI) 1.45 to 5.61) and 'investigator-rated
      global degree of improvement' (standardised mean difference (SMD) 5.74, 95% CI
      4.26 to 7.23).When mometasone furoate 0.05% was compared to placebo in another
      trial, there was a significant improvement in the 'investigator-rated change in
      clinical grade of phimosis' (SMD -1.04, 95% CI -1.77 to -0.31).Both trials found
      no significant differences in reported adverse drug reactions between the
      corticosteroid and placebo groups. The data from four trials found no significant
      benefit for topical testosterone, dihydrotestosterone, and progesterone. When
      used as maintenance therapy after an initial treatment with topical clobetasol
      propionate in another trial, topical testosterone worsened the symptoms (P <
      0.05), but the placebo did not.One trial found no differences between
      pimecrolimus and clobetasol propionate in relieving symptoms through change in
      pruritus (itching) (SMD -0.33, 95% CI -0.99 to 0.33) and burning/pain (SMD 0.03,
      95% CI -0.62 to 0.69). However, pimecrolimus was less effective than clobetasol
      propionate with regard to the 'investigator-rated global degree of improvement'
      (SMD -1.64, 95% CI -2.40 to -0.87). This trial found no significant differences
      in reported adverse drug reactions between the pimecrolimus and placebo groups.
      AUTHORS' CONCLUSIONS: The current limited evidence demonstrates the efficacy of
      clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital
      lichen sclerosus. Further RCTs are needed to determine the optimal potency and
      regimen of topical corticosteroids, examine other topical interventions, assess
      the duration of remission or prevention of flares, evaluate the reduction in the
      risk of genital squamous cell carcinoma or genital intraepithelial neoplasia, and
      examine the efficacy in improving the quality of the sex lives of people with
      this condition.

PMID- 22161425
TI  - Information interventions for orienting patients and their carers to cancer care
      facilities.
AB  - BACKGROUND: Cancer patients experience distress and anxiety related to their
      diagnosis, treatment and the unfamiliar cancer centre. Strategies with the aim of
      orienting patients to a cancer care facility may improve patient outcomes.
      Although meeting patients' information needs at different stages is important,
      there is little agreement about the type of information and the timing for
      information to be given. Orientation interventions aim to address information
      needs at the start of a person's experience with a cancer care facility. The
      extent of any benefit of these interventions is unknown. OBJECTIVES: To assess
      the effects of information interventions which orient patients and their
      carers/family to a cancer care facility, and to the services available in the
      facility. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2011, Issue 2); MEDLINE (OvidSP) (1966 to
      Jun 2011), EMBASE (Ovid SP) (1966 to Jun 2011), CINAHL (EBSCO) (1982 to Jun
      2011), PsycINFO (OvidSP) (1966 to Jun 2011), review articles and reference lists
      of relevant articles. We contacted principal investigators and experts in the
      field. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster RCTs and
      quasi-RCTs evaluating the effects of information interventions that orient
      patients and their carers/family to a cancer care facility. DATA COLLECTION AND
      ANALYSIS: Results of searches were reviewed against the pre-determined criteria
      for inclusion by two review authors. The primary outcomes were knowledge and
      understanding; health status and wellbeing, evaluation of care, and harms.
      Secondary outcomes were communication, skills acquisition, behavioural outcomes,
      service delivery, and health professional outcomes. We pooled results of RCTs
      using mean differences (MD) and 95% confidence intervals (CI). MAIN RESULTS: We
      included four RCTs involving 610 participants. All four trials aimed to
      investigate the effects of orientation programs for cancer patients to a cancer
      facility. There was high risk of bias across studies. Findings from two of the
      RCTs demonstrated significant benefits of the orientation intervention in
      relation to levels of distress (mean difference (MD) -8.96 (95% confidence
      interval (CI) -11.79 to -6.13), but non-significant benefits in relation to state
      anxiety levels (MD -9.77 (95% CI -24.96 to 5.41). Other outcomes for participants
      were generally positive (e.g. more knowledgeable about the cancer centre and
      cancer therapy, better coping abilities). No harms or adverse effects were
      measured or reported by any of the included studies. There were insufficient data
      on the other outcomes of interest. AUTHORS' CONCLUSIONS: This review has
      demonstrated the feasibility and some potential benefits of orientation
      interventions. There was a low level of evidence suggesting that orientation
      interventions can reduce distress in patients. However, most of the other
      outcomes remain inconclusive (patient knowledge recall/ satisfaction). The
      majority of studies were subject to high risk of bias, and were likely to be
      insufficiently powered. Further well conducted and powered RCTs are required to
      provide evidence for determining the most appropriate intensity, nature, mode and
      resources for such interventions. Patient and carer-focused outcomes should be
      included.

PMID- 22161426
TI  - Ayurvedic treatments for diabetes mellitus.
AB  - BACKGROUND: Patients with diabetes frequently use complimentary and alternative
      medications including Ayurvedic medications and hence it is important to
      determine their efficacy and safety. OBJECTIVES: To assess the effects of
      Ayurvedic treatments for diabetes mellitus. SEARCH METHODS: We searched The
      Cochrane Library (issue 10, 2011), MEDLINE (until 31 August 2011), EMBASE (until
      31 August 2011), AMED (until 14 October 2011), the database of randomised trials
      from South Asia (until 14 October 2011), the database of the grey literature
      (OpenSigle, until 14 October 2011) and databases of ongoing trials (until 14
      October 2011). In addition we performed hand searches of several journals and
      reference lists of potentially relevant trials. SELECTION CRITERIA: We included
      randomized trials of at least two months duration of Ayurvedic interventions for
      diabetes mellitus. Participants of both genders, all ages and any type of
      diabetes were included irrespective of duration of diabetes, antidiabetic
      treatment, comorbidity or diabetes related complications. DATA COLLECTION AND
      ANALYSIS: Two authors independently extracted data. Risk of bias of trials was
      evaluated as indicated in the Cochrane Handbook for Systematic Reviews of
      Intervention. MAIN RESULTS: Results of only a limited number of studies could be
      combined, in view of different types of interventions and variable quality of
      data. We found six trials of proprietary herbal mixtures and one of whole system
      Ayurvedic treatment. These studies enrolled 354 participants ( 172 on treatment,
      158 on controls, 24 allocation unknown). The treatment duration ranged from 3 to
      6 months. All these studies included adults with type 2 diabetes mellitus.With
      regard to our primary outcomes, significant reductions in glycosylated
      haemoglobin A1c (HbA1c), fasting blood sugar (FBS) or both were observed with
      Diabecon, Inolter and Cogent DB compared to placebo or no additional treatment,
      while no significant hypoglycaemic response was found with Pancreas tonic and
      Hyponidd treatment. The study of whole system Ayurvedic treatment did not provide
      data on HbA1c and FBS values. One study of Pancreas tonic treatment did not
      detect a significant change in health-related quality of life. The main adverse
      effects reported were drug hypersensitivity (one study, one patient in the
      treatment arm); hypoglycaemic episodes (one study, one participant in the
      treatment arm; none had severe hypoglycaemia) and gastrointestinal side effects
      in one study (1 of 20 in the intervention group and 0 of 20 participants in the
      control group). None of the included studies reported any deaths, renal,
      hematological or liver toxicity.With regard to our secondary outcomes, post
      prandial blood sugar (PPBS) was lower among participants treated with Diabecon,
      was unchanged with Hyponidd and was higher in patients treated with Cogent DB.
      Treatment with Pancreas tonic and Hyponidd did not affect lipid profile
      significantly, while patients treated with Inolter had significantly higher HDL-
      and lower LDL-cholesterol as well as lower triglycerides. Cogent DB treated
      participants also had lower total cholesterol and triglycerides.Studies of
      treatment with Diabecon reported increased fasting insulin levels; one study of
      treatment with Diabecon reported higher stimulated insulin levels and fasting C
      peptide levels in the treatment group. There was no significant difference in
      fasting and stimulated C-peptide and insulin levels with Hyponidd, Cogent DB and
      Pancreas tonic treatment. The study of Inolter did not assess these outcomes.No
      study reported on or was designed to investigate diabetic complications, death
      from any cause and economic data. AUTHORS' CONCLUSIONS: Although there were
      significant glucose-lowering effects with the use of some herbal mixtures, due to
      methodological deficiencies and small sample sizes we are unable to draw any
      definite conclusions regarding their efficacy. Though no significant adverse
      events were reported, there is insufficient evidence at present to recommend the
      use of these interventions in routine clinical practice and further studies are
      needed.

PMID- 22161427
TI  - Local intramuscular transplantation of autologous mononuclear cells for critical
      lower limb ischaemia.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a major health problem and in
      about 1% to 2% of patients the disease progresses to critical limb ischaemia
      (CLI). In a substantial number of patients with CLI, no effective treatment
      option other than amputation is available and around a quarter of these patients
      will require a major amputation during the following year. OBJECTIVES: To
      determine the effectiveness and safety of autologous adult bone marrow derived
      mononuclear cells (BMMNCs) as a treatment for CLI. SEARCH METHODS: The Cochrane
      Peripheral Vascular Diseases Group searched their Specialised Register (last
      searched November 2010) and CENTRAL (2010, Issue 4). We searched the reference
      lists of identified articles. SELECTION CRITERIA: All randomised controlled
      trials of CLI in which participants were randomly allocated to intramuscular
      administration of autologous adult BMMNCs or control (either no intervention or
      conventional conservative therapy) were included. Studies on patients with
      intermittent claudication were not included. DATA COLLECTION AND ANALYSIS: Two
      authors independently selected trials, assessed trials for eligibility and
      methodological quality, and extracted data. Disagreements were resolved by
      consensus or by the third author. MAIN RESULTS: Thirty-seven potential studies
      were identified after initial screening of titles and abstracts. Only two small
      studies, with a combined total of 57 patients, met our inclusion criteria and
      were finally included. In one study the effects of intramuscular injections of
      BMMNCs in the ischaemic lower limbs of patients with CLI were compared with
      control (standard conservative treatment). No deaths were reported and no
      significant difference was observed between the two groups for either pain (P =
      0.37) or the ankle brachial pressure index (ABI) parameter. However, the
      treatment group showed a significantly smaller proportion of participants
      undergoing amputation compared with the control group (P = 0.026).In the other
      study, following subcutaneous injections of granulocyte colony-stimulating factor
      (G-CSF) for five days peripheral blood derived mononuclear cells were collected
      and then transplanted by intramuscular injections into ischaemic lower limbs. The
      effects were compared with daily intravenous prostaglandin E1 injections (control
      group). No deaths were reported. Pain reduction was greater in the treatment
      group than in the control group (P < 0.001) as was increase in ABI (mean increase
      0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically
      significant increase in pain-free walking distance compared with the control
      group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of
      participants underwent amputation in the treatment group compared with the
      control group (0% versus 36%, P = 0.007). AUTHORS' CONCLUSIONS: The data from the
      published trials suggest that there is insufficient evidence to support this
      treatment. These results were based on only two trials which had a very small
      number of participants. Therefore evidence from larger randomised controlled
      trials is needed in order to provide adequate statistical power to assess the
      role of intramuscular mononuclear cell implantation in patients with CLI.

PMID- 22161428
TI  - Statins for multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease of
      the human central nervous system. Statins, prescribed as cholesterol lowering
      agents, have shown possible effects for treating MS in experimental and
      preliminary clinical studies. OBJECTIVES: To evaluate the efficacy and safety of
      statins administered alone or as add-on to approved treatments for MS. SEARCH
      METHODS: The Trials Search Coordinator searched the Cochrane MS Group Trials
      Register (1 August 2011). We searched the Chinese National Knowledge
      Infrastructure (CNKI) (1979 to 1 August 2011), trials registers and conference
      proceedings. Pharmaceutical companies and authors of included studies were
      contacted for additional information.There were no language restrictions.
      SELECTION CRITERIA: Randomised controlled trials comparing statins with placebo,
      or comparing statins in combination with approved treatments alone for patients
      with MS. DATA COLLECTION AND ANALYSIS: Three review authors independently
      assessed trial quality and extracted data. MAIN RESULTS: Four trials involving
      458 participants were included. All trials compared statins (two evaluating
      atorvastatin and two simvastatin) plus interferon beta-1a with interferon beta-1a
      alone for treating MS. The methodological quality was good for three studies and
      poor for remaining one. None of them showed statistically significant difference
      between both treatment groups in reducing relapses, preventing disease
      progression or developing new T2 or gadolinium-enhanced lesions on MRI after 9,
      12, 24 months follow up period. Statins resulted to be safe and well tolerated,
      no serious adverse effects were reported. Changes on quality of life after
      receiving statins were not reported in the trials. AUTHORS' CONCLUSIONS: There is
      no convincing evidence to support the use of either atorvastatin or simvastatin
      as an adjunctive therapy in MS.

PMID- 22161429
TI  - Remote ischaemic preconditioning versus no remote ischaemic preconditioning for
      vascular and endovascular surgical procedures.
AB  - BACKGROUND: Despite advances in perioperative care, elective major vascular
      surgical procedures carry a significant risk of morbidity and mortality. Remote
      ischaemic preconditioning is initiated by brief, non-lethal periods of ischaemia
      in a vascular bed different from the one which will be subjected to ischaemic
      insult during surgery. It has the potential to provide local tissue protection
      from further prolonged periods of ischaemia. OBJECTIVES: The aim of this review
      was to compare the outcomes from vascular and endovascular surgical procedures
      with and without the use of remote ischaemic preconditioning. SEARCH METHODS: The
      Cochrane Peripheral Vascular Diseases Group searched their Specialised Register
      (June 2011) and CENTRAL (2011, Issue 2). The authors searched MEDLINE via PubMed
      (July 2011), EMBASE (June 2011), and Science Citation Index Expanded (July 2011).
      SELECTION CRITERIA: We considered for inclusion all randomised controlled trials
      that evaluated the role of remote ischaemic preconditioning in reducing mortality
      and systemic injury in patients undergoing open vascular or endovascular surgery.
      DATA COLLECTION AND ANALYSIS: We collected the data on characteristics of the
      trial, methodological quality, the remote ischaemic preconditioning stimulus
      used, mortality, morbidity, operating time and hospital stay from each trial. We
      analysed the data with both the fixed-effect and the random-effects models using
      RevMan analysis. For each outcome we calculated the risk ratio (RR) or mean
      difference with 95% confidence interval (CI) based on an intention-to-treat
      analysis. MAIN RESULTS: We included four studies with a total of 115 patients
      randomised to undergo a vascular procedure with remote ischaemic preconditioning
      and 117 patients randomised to have the procedure without remote ischaemic
      preconditioning. None of the trials were of low risk of bias. There was no
      significant difference in mortality between the two groups (RR 1.70, 95% CI 0.51
      to 5.72). Similarly, there was no statistically significant difference between
      the two groups for all other outcomes except reduced risk of myocardial
      infarction in the remote ischaemic preconditioning group, which was significant
      by the fixed-effect model (RR 0.31, 95% CI 0.10 to 0.90) but not by the random
      effects model (RR 0.34, 95% CI 0.11 to 1.08). This positive effect was from the
      results of only one trial and was not consistently observed. Furthermore, it was
      noted that there was an observed trend of high incidence of unplanned critical
      care admission in the remote ischaemic preconditioning group, although this was
      not statistically significant (RR 2.15, 95% CI 0.87 to 5.33). AUTHORS'
      CONCLUSIONS: Based on current evidence from small pilot trials, there are too few
      data to be able to say whether remote ischaemic preconditioning has any
      beneficial or harmful effects. The safety of this technique needs to be confirmed
      in adequately powered trials. Therefore, further randomised trials on this
      technique are required.

PMID- 22161430
TI  - Computer-assisted versus oral-and-written dietary history taking for diabetes
      mellitus.
AB  - BACKGROUND: Diabetes is a chronic illness characterised by insulin resistance or
      deficiency, resulting in elevated glycosylated haemoglobin A1c (HbA1c) levels.
      Diet and adherence to dietary advice is associated with lower HbA1c levels and
      control of disease. Dietary history may be an effective clinical tool for
      diabetes management and has traditionally been taken by oral-and-written methods,
      although it can also be collected using computer-assisted history taking systems
      (CAHTS). Although CAHTS were first described in the 1960s, there remains
      uncertainty about the impact of these methods on dietary history collection,
      clinical care and patient outcomes such as quality of life.  OBJECTIVES: To
      assess the effects of computer-assisted versus oral-and-written dietary history
      taking on patient outcomes for diabetes mellitus. SEARCH METHODS: We searched The
      Cochrane Library (issue 6, 2011), MEDLINE (January 1985 to June 2011), EMBASE
      (January 1980 to June 2011) and CINAHL (January 1981 to June 2011). Reference
      lists of obtained articles were also pursued further and no limits were imposed
      on languages and publication status. SELECTION CRITERIA: Randomised controlled
      trials of computer-assisted versus oral-and-written history taking in patients
      with diabetes mellitus. DATA COLLECTION AND ANALYSIS: Two authors independently
      scanned the title and abstract of retrieved articles. Potentially relevant
      articles were investigated as full text. Studies that met the inclusion criteria
      were abstracted for relevant population and intervention characteristics with any
      disagreements resolved by discussion, or by a third party. Risk of bias was
      similarly assessed independently. MAIN RESULTS: Of the 2991 studies retrieved,
      only one study with 38 study participants compared the two methods of history
      taking over a total of eight weeks. The authors found that as patients became
      increasingly familiar with using CAHTS, the correlation between patients' food
      records and computer assessments improved. Reported fat intake decreased in the
      control group and increased when queried by the computer. The effect of the
      intervention on the management of diabetes mellitus and blood glucose levels was
      not reported. Risk of bias was considered moderate for this study. AUTHORS'
      CONCLUSIONS: Based on one small study judged to be of moderate risk of bias, we
      tentatively conclude that CAHTS may be well received by study participants and
      potentially offer time saving in practice. However, more robust studies with
      larger sample sizes are needed to confirm these. We cannot draw on any
      conclusions in relation to any other clinical outcomes at this stage.

PMID- 22161431
TI  - Computer-assisted versus oral-and-written family history taking for identifying
      people with elevated risk of type 2 diabetes mellitus.
AB  - BACKGROUND: Diabetes is a chronic illness characterised by insulin resistance or
      deficiency, resulting in elevated glycosylated haemoglobin A1c (HbA1c) levels.
      Because diabetes tends to run in families, the collection of data is an important
      tool for identifying people with elevated risk of type2 diabetes. Traditionally,
      oral-and-written data collection methods are employed but computer-assisted
      history taking systems (CAHTS) are increasingly used. Although CAHTS were first
      described in the 1960s, there remains uncertainty about the impact of these
      methods on family history taking, clinical care and patient outcomes such as
      health-related quality of life.  OBJECTIVES: To assess the effectiveness of
      computer-assisted versus oral-and-written family history taking for identifying
      people with elevated risk of developing type 2 diabetes mellitus. SEARCH METHODS:
      We searched The Cochrane Library (issue 6, 2011), MEDLINE (January 1985 to June
      2011), EMBASE (January 1980 to June 2011) and CINAHL (January 1981 to June 2011).
      Reference lists of obtained articles were also pursued further and no limits were
      imposed on languages and publication status. SELECTION CRITERIA: Randomised
      controlled trials of computer-assisted versus oral-and-written history taking in
      adult participants (16 years and older). DATA COLLECTION AND ANALYSIS: Two
      authors independently scanned the title and abstract of retrieved articles.
      Potentially relevant articles were investigated as full text. Studies that met
      the inclusion criteria were abstracted for relevant population and intervention
      characteristics with any disagreements resolved by discussion, or by a third
      party. Risk of bias was similarly assessed independently. MAIN RESULTS: We found
      no controlled trials on computer-assisted versus oral-and-written family history
      taking for identifying people with elevated risk of type 2 diabetes mellitus.
      AUTHORS' CONCLUSIONS: There is a need to develop an evidence base to support the
      effective development and use of computer-assisted history taking systems in this
      area of practice. In the absence of evidence on effectiveness, the implementation
      of computer-assisted family history taking for identifying people with elevated
      risk of type 2 diabetes may only rely on the clinicians' tacit knowledge,
      published monographs and viewpoint articles.

PMID- 22161432
TI  - Customised versus population-based growth charts as a screening tool for
      detecting small for gestational age infants in low-risk pregnant women.
AB  - BACKGROUND: Fetal growth restriction is defined as failure to reach growth
      potential and considered one of the major complications of pregnancy. These
      infants are often, although not universally, small for gestational age (SGA). SGA
      is defined as a weight less than a specified percentile (usually the 10th
      percentile). Identification of SGA infants is important because these infants are
      at increased risk of perinatal morbidity and mortality. Screening for SGA is a
      challenge for all maternity care providers and current methods of clinical
      assessment fail to detect many infants that are SGA. Large observational studies
      suggest that customised growth charts may be better able to differentiate between
      constitutional and pathologic smallness. Customised charts adjust for
      physiological variables such as maternal weight and height, ethnicity and parity.
      OBJECTIVES: To assess the benefits and harms of using population-based growth
      charts compared with customised growth charts as a screening tool for detection
      of fetal growth in pregnant women. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (30 September 2011), reviewed
      published guidelines and searched the reference lists of review articles.
      SELECTION CRITERIA: Randomised, quasi-randomised or cluster randomised clinical
      trials comparing customised versus population-based growth charts used as a
      screening tool for detection of fetal growth in pregnant women. DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed trials for inclusion.
      MAIN RESULTS: No randomised trials met the inclusion criteria. AUTHORS'
      CONCLUSIONS: There is no randomised trial evidence currently available. Further
      randomised trials are required to accurately assess whether the improvement in
      detection shown is secondary to customised charts alone or an effect of the
      policy change. Future research in large trials is needed to investigate the
      benefits and harms (including perinatal mortality) of using customised growth
      charts in different settings and for both fundal height and ultrasound
      measurements.

PMID- 22161433
TI  - Second-generation antidepressants for seasonal affective disorder.
AB  - BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent
      depressive episodes that is often treated with second-generation antidepressants
      (SGAs), light therapy or psychotherapy. OBJECTIVES: To assess the efficacy and
      safety of SGAs for the treatment of SAD in adults in comparison with placebo,
      light therapy, other SGAs or psychotherapy. SEARCH METHODS: We searched the
      Cochrane Depression, Anxiety and Neuorosis Review Group's specialised register
      (CCDANCTR) on the 26 August 2011. The CCDANCTR contains reports of relevant
      randomised controlled trials from The Cochrane Library (all years), EMBASE (1974
      to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). In addition, we
      searched pharmaceutical industry trials registers via the Internet to identify
      unpublished trial data. Furthermore, we searched OVID MEDLINE, MEDLINE In
      process, EMBASE and PsycINFO to 27July 2011 for publications on adverse effects
      (including non-randomised studies). SELECTION CRITERIA: For efficacy we included
      randomised trials of SGAs compared with other SGAs, placebo, light therapy or
      psychotherapy in adult participants with SAD. For adverse effects we also
      included non-randomised studies. DATA COLLECTION AND ANALYSIS: Two review authors
      screened abstracts and full-text publications against the inclusion criteria.
      Data abstraction and risk of bias assessment were conducted by one reviewer and
      checked for accuracy and completeness by a second. We pooled data for meta
      analysis where the participant groups were similar and the studies assessed the
      same treatments with the same comparator and had similar definitions of outcome
      measures over a similar duration of treatment. MAIN RESULTS: For efficacy we
      included three randomised trials of between five and eight weeks duration with a
      total of 204 participants. For adverse effects we included two randomised trials
      and three observational (non-randomised) studies of five to eight weeks duration
      with a total of 225 participants. Overall, the randomised trials had low-to
      moderate risk of bias, and the observational studies had a high risk of bias (due
      to small size and high attrition). The participants in the studies all met DSM
      (Diagnostic and Statistics Manual of Mental Disorders) criteria for SAD. The
      average age was approximately 40 years and 70% of the participants were
      female.Results from one trial with 68 participants showed that fluoxetine was not
      significantly more effective than placebo in achieving clinical response (risk
      ratio (RR) 1.62, 95% confidence interval (CI) 0.92 to 2.83). The number of
      adverse effects were similar between the two groups.We located two trials that
      contained a total of 136 participants for the comparison fluoxetine versus light
      therapy. Our meta-analysis of the results of the two trials showed fluoxetine and
      light therapy to be approximately equal in treating seasonal depression: RR of
      response 0.98 (95% CI 0.77 to 1.24), RR of remission 0.81 (95% CI 0.39 to 1.71).
      The number of adverse effects was similar in both groups.Two of the three
      randomised trials and three non-randomised studies contained adverse effect data
      on 225 participants who received fluoxetine, escitalopram, duloxetine,
      reboxetine, light therapy or placebo. We were only able to obtain crude rates of
      adverse effects, so any interpretation of this needs to be undertaken with
      caution. Between 22% and 100% of participants who received a SGA suffered an
      adverse effect and between 15% and 27% of participants withdrew from the studies
      because of adverse effects. AUTHORS' CONCLUSIONS: Evidence for the effectiveness
      of SGAs is limited to one small trial of fluoxetine compared with placebo, which
      shows a non-significant effect in favour of fluoxetine, and two small trials
      comparing fluoxetine against light therapy, which suggest equivalence between the
      two interventions. The lack of available evidence precludes the ability to draw
      any overall conclusions on the use of SGAs for SAD. Further larger RCTs are
      required to expand and strengthen the evidence base on this topic, and should
      also include comparisons with psychotherapy and other SGAs.Data on adverse events
      were sparse, and a comparative analysis was not possible. Therefore the data we
      obtained on adverse effects is not robust and our confidence in the data is
      limited. Overall, up to 27% of participants treated with SGAs for SAD withdrew
      from the studies early due to adverse effects. The overall quality of evidence in
      this review is very low.

PMID- 22161434
TI  - Cardiac testing for coronary artery disease in potential kidney transplant
      recipients.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk of
      coronary artery disease (CAD) and adverse cardiac events. Screening for CAD is
      therefore an important part of preoperative evaluation for kidney transplant
      candidates. There is significant interest in the role of non-invasive cardiac
      investigations and their ability to identify patients at high risk of CAD. 
      OBJECTIVES: We investigated the accuracy of non-invasive cardiac screening tests
      compared with coronary angiography to detect CAD in patients who are potential
      kidney transplant recipients. SEARCH METHODS: MEDLINE and EMBASE searches
      (inception to November 2010) were performed to identify studies that assessed the
      diagnostic accuracy of non-invasive screening tests, using coronary angiography
      as the reference standard. We also conducted citation tracking via Web of Science
      and handsearched reference lists of identified primary studies and review
      articles.   SELECTION CRITERIA: We included in this review all diagnostic cross
      sectional, cohort and randomised studies of test accuracy that compared the
      results of any cardiac test with coronary angiography (the reference standard)
      relating to patients considered as potential candidates for kidney
      transplantation or kidney-pancreas transplantation at the time diagnostic tests
      were performed.  DATA COLLECTION AND ANALYSIS: We used a hierarchical modelling
      strategy to produce summary receiver operating characteristic (SROC) curves, and
      pooled estimates of sensitivity and specificity. Sensitivity analyses to
      determine test accuracy were performed if only studies that had full verification
      or applied a threshold of >= 70% stenosis on coronary angiography for the
      diagnosis of significant CAD were included. MAIN RESULTS: The following screening
      investigations included in the meta-analysis were: dobutamine stress
      echocardiography (DSE) (13 studies), myocardial perfusion scintigraphy (MPS)
      (nine studies), echocardiography (three studies), exercise stress
      electrocardiography (two studies), resting electrocardiography (three studies),
      and one study each of electron beam computed tomography (EBCT), exercise
      ventriculography, carotid intimal media thickness (CIMT) and digital subtraction
      fluorography (DSF). Sufficient studies were present to allow hierarchical summary
      receiver operating characteristic (HSROC) analysis for DSE and MPS. When
      including all available studies, both DSE and MPS had moderate sensitivity and
      specificity in detecting coronary artery stenosis in patients who are kidney
      transplant candidates [DSE (13 studies) - pooled sensitivity 0.79 (95% CI 0.67 to
      0.88), pooled specificity 0.89 (95% CI 0.81 to 0.94); MPS (nine studies) - pooled
      sensitivity 0.74 (95% CI 0.54 to 0.87), pooled specificity 0.70 (95% CI 0.51 to
      0.84)]. When limiting to studies which defined coronary artery stenosis using a
      reference threshold of >= 70% stenosis on coronary angiography, there was little
      change in these pooled estimates of accuracy [DSE (9 studies) - pooled
      sensitivity 0.76 (95% CI 0.60 to 0.87), specificity 0.88 (95% CI 0.78 to 0.94);
      MPS (7 studies) - pooled sensitivity 0.67 (95% CI 0.48 to 0.82), pooled
      specificity 0.77 (95% CI 0.61 to 0.88)]. There was evidence that DSE had improved
      accuracy over MPS (P = 0.02) when all studies were included in the analysis, but
      this was not significant when we excluded studies which did not avoid partial
      verification or use a reference standard threshold of >=70% stenosis (P = 0.09). 
      AUTHORS' CONCLUSIONS: DSE may perform better than MPS but additional studies
      directly comparing these cardiac screening tests are needed. Absence of
      significant CAD may not necessarily correlate with cardiac-event free survival
      following transplantation. Further research should focus on assessing the ability
      of functional tests to predict postoperative outcome.

PMID- 22161435
TI  - Lamivudine with or without adefovir dipivoxil for postoperative hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a significant cause of death,
      especially in Asia and sub-Saharan Africa. Removal of the cancer through surgery
      or other techniques is considered the first-line therapy in early HCC, but
      relapse of HCC is the main postoperative problem. The main risk factor for HCC is
      hepatitis B virus (HBV) infection. Lamivudine and adefovir dipivoxil are
      effective and tolerable for chronic hepatitis B by suppressing the viral load and
      to reduce fibrosis in the liver.   OBJECTIVES: To assess the benefits and harms
      of postoperative administration of lamivudine with or without adefovir dipivoxil
      in participants with surgically treated HCC and chronic HBV infection or HBV
      carrier state. SEARCH METHODS: A systematic search was performed in The Cochrane
      Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science
      Citation Index Expanded (SCI Exp) in October 2011. Further trials have been
      sought through scanning reference lists of relevant articles. SELECTION CRITERIA:
      Randomised clinical trials comparing the administration of lamivudine with and
      without adefovir dipivoxil for participants with ablation treated HCC (surgical
      or through other techniques) and chronic HBV infection or HBV carrier state,
      regardless of publication status, language, blinding, and publication status,
      were to be included in this review. We planned to extract data on harms from
      quasi-randomised studies or cohort studies when retrieved with the search
      results. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies
      for inclusion, and extracted and analysed the data. The type and number of
      adverse events were reported descriptively. MAIN RESULTS: No randomised trials
      could be included into this systematic review. Thus, we were unable to follow our
      pre-published protocol and perform meta-analyses.Through our searches for
      randomised clinical trials, four cohort trials with 230 participants were
      retrieved. We read them in order to find data on harm, ie, adverse events.
      Breakthrough hepatitis was a serious adverse event attributable to lamivudine. No
      other adverse events seemed to be caused by the administration of lamivudine or
      adefovir dipivoxil were reported in the four cohort studies. AUTHORS'
      CONCLUSIONS: No evidence from randomised trials on the beneficial or harmful
      effects of lamivudine with or without adefovir dipivoxil for postoperative HCC
      was found. Randomised clinical trials with large number of participants and long
      follow-up period should be carried out to direct clinical practice.

PMID- 22161436
TI  - Use of electronic health records to support smoking cessation.
AB  - BACKGROUND: Health information systems such as electronic health records (EHR),
      computerized decision support systems, and electronic prescribing are potentially
      valuable components to improve the quality and efficiency of clinical
      interventions for tobacco use. OBJECTIVES: To assess the effectiveness of
      electronic health record-facilitated interventions on smoking cessation support
      actions by clinicians and on patient smoking cessation outcomes. SEARCH METHODS:
      We searched the Cochrane Tobacco Addiction Group Specialised Register, CENTRAL,
      MEDLINE, EMBASE, PsycINFO, CINAHL, and reference lists and bibliographies of
      included studies. We searched for studies published between January 1990 and May
      2011. SELECTION CRITERIA: We included both randomized studies and non-randomized
      studies that reported interventions targeting tobacco use through an EHR in
      health care settings. The intervention could include any use of an EHR to improve
      smoking status documentation or cessation assistance for patients who use
      tobacco, either by direct action or by feedback of clinical performance measures.
      DATA COLLECTION AND ANALYSIS: Characteristics and content of the interventions,
      participants, outcomes and methods of the included studies were extracted by one
      author and checked by a second. Because few randomized studies existed, we did
      not conduct a meta-analysis. MAIN RESULTS: We included three randomized and eight
      non-randomized observational studies of fair to good quality that tested the use
      of an existing EHR to improve documentation and/or treatment of tobacco use. None
      of the studies included a direct assessment of patient quit rates. Overall, these
      studies found only modest improvements in some of the recommended clinician
      actions steps on tobacco use. AUTHORS' CONCLUSIONS: At least in the short term,
      documentation of tobacco status and increased referral to cessation counseling do
      appear to increase following the introduction of an expectation to use the EHR to
      record and treat patient tobacco use at medical visits. There is a need for
      additional research to further understand the effect of EHRs on smoking treatment
      in healthcare settings.

PMID- 22161437
TI  - Sclerotherapy for lower limb telangiectasias.
AB  - BACKGROUND: Sclerotherapy has been used in clinical practice for centuries, but
      there is still no consensus about which, if any, sclerosing agent provides the
      best results. OBJECTIVES: To assess the effectiveness and safety of sclerosing
      agents in the treatment of telangiectasias of the lower limbs. SEARCH METHODS:
      The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialised
      Register (last searched 26 May 2011) and CENTRAL (2011, Issue 2). We searched
      references within identified studies and from the Cited References in the Web of
      Science. We contacted study authors and pharmaceutical companies. There were no
      language restrictions. SELECTION CRITERIA: We included randomised or quasi
      randomised controlled trials on the treatment of telangiectasias comparing
      sclerotherapy with a normal saline placebo, no treatment or an alternative
      sclerotherapy regimen. DATA COLLECTION AND ANALYSIS: Both authors determined
      which studies to include, extracted the data and rated risk of bias. One author
      (LS) contacted study authors and pharmaceutical companies and analysed the
      results. MAIN RESULTS: Ten studies involving 484 patients were included. There
      was no evidence suggesting superior efficacy of any one sclerosant over another,
      but there was evidence of superiority of sclerotherapy to placebo.The evidence
      did not suggest an increase in patient satisfaction with any one agent versus
      another, but there was evidence that patients were less satisfied with
      placebo.There was some evidence suggesting that polidocanol (POL) was more likely
      to cause adverse reactions at a concentration of 1% compared with lower
      concentrations or hypertonic saline, and that sodium tetradecyl sulfate (STS) was
      more likely to cause adverse reactions at a concentration of 1% compared with POL
      at 0.5%.There was some evidence suggesting that STS was more painful than POL,
      heparsal (20% saline mixed with heparin 100 units/mL) or placebo, and that POL
      was no more painful than placebo. Evidence from one study suggested that
      hypertonic saline (HS) was more painful than POL.The data were not suitable for
      meta-analysis. AUTHORS' CONCLUSIONS: The evidence did not suggest superior
      efficacy or patient satisfaction for any one sclerosing agent used in the
      treatment of telangiectasias of the lower limbs, but the agents studied showed
      superiority to a normal saline placebo. However, the amount of available evidence
      in this field is small and the overall methodological quality of the research was
      poor, as was the quality of reporting. More research is needed to determine the
      optimal agent(s) and the ideal dosing to achieve the best results and maximize
      patient satisfaction. Future research efforts should incorporate more demographic
      data and symptom measures to allow for comparison with findings from
      observational studies, thereby aiding assessment of how various risk groups
      respond to treatment.

PMID- 22161438
TI  - Flossing for the management of periodontal diseases and dental caries in adults.
AB  - BACKGROUND: Good oral hygiene is thought to be important for oral health. This
      review is to determine the effectiveness of flossing in addition to toothbrushing
      for preventing gum disease and dental caries in adults. OBJECTIVES: To assess the
      effects of flossing in addition to toothbrushing, as compared with toothbrushing
      alone, in the management of periodontal diseases and dental caries in adults.
      SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral
      Health Group Trials Register (to 17 October 2011), the Cochrane Central Register
      of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), MEDLINE via
      OVID (1950 to 17 October 2011), EMBASE via OVID (1980 to 17 October 2011), CINAHL
      via EBSCO (1980 to 17 October 2011), LILACS via BIREME (1982 to 17 October 2011),
      ZETOC Conference Proceedings (1980 to 17 October 2011), Web of Science Conference
      Proceedings (1990 to 17 October 2011), Clinicaltrials.gov (to 17 October 2011)
      and the metaRegister of Controlled Clinical Trials (to 17 October 2011). We
      imposed no restrictions regarding language or date of publication. We contacted
      manufacturers of dental floss to identify trials. SELECTION CRITERIA: We included
      randomised controlled trials conducted comparing toothbrushing and flossing with
      only toothbrushing, in adults. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed risk of bias for the included studies and extracted data.
      We contacted trial authors for further details where these were unclear. The
      effect measure for each meta-analysis was the standardised mean difference (SMD)
      with 95% confidence intervals (CI) using random-effects models. We examined
      potential sources of heterogeneity, along with sensitivity analyses omitting
      trials at high risk of bias. MAIN RESULTS: Twelve trials were included in this
      review, with a total of 582 participants in flossing plus toothbrushing
      (intervention) groups and 501 participants in toothbrushing (control) groups. All
      included trials reported the outcomes of plaque and gingivitis. Seven of the
      included trials were assessed as at unclear risk of bias and five were at high
      risk of bias.Flossing plus toothbrushing showed a statistically significant
      benefit compared to toothbrushing in reducing gingivitis at the three time points
      studied, the SMD being -0.36 (95% CI -0.66 to -0.05) at 1 month, SMD -0.41 (95%
      CI -0.68 to -0.14) at 3 months and SMD -0.72 (95% CI -1.09 to -0.35) at 6 months.
      The 1-month estimate translates to a 0.13 point reduction on a 0 to 3 point scale
      for Loe-Silness gingivitis index, and the 3 and 6 month results translate to 0.20
      and 0.09 reductions on the same scale.Overall there is weak, very unreliable
      evidence which suggests that flossing plus toothbrushing may be associated with a
      small reduction in plaque at 1 or 3 months.None of the included trials reported
      data for the outcomes of caries, calculus, clinical attachment loss, or quality
      of life. There was some inconsistent reporting of adverse effects. AUTHORS'
      CONCLUSIONS: There is some evidence from twelve studies that flossing in addition
      to toothbrushing reduces gingivitis compared to toothbrushing alone. There is
      weak, very unreliable evidence from 10 studies that flossing plus toothbrushing
      may be associated with a small reduction in plaque at 1 and 3 months. No studies
      reported the effectiveness of flossing plus toothbrushing for preventing dental
      caries.

PMID- 22161439
TI  - Interventions for treating anxiety after stroke.
AB  - BACKGROUND: Approximately 20% of stroke patients experience anxiety at some point
      after stroke. OBJECTIVES: To determine if any treatment for anxiety after stroke
      decreases the proportion of patients with anxiety disorders or symptoms, and to
      determine the effect of treatment on quality of life, disability, depression,
      social participation, risk of death or caregiver burden. SEARCH METHODS: We
      searched the trials register of the Cochrane Stroke Group (October 2010), CENTRAL
      (The Cochrane Library 2010, Issue 4), MEDLINE (1950 to October 2010), EMBASE
      (1947 to October 2010), PsycINFO (1806 to October 2010), Allied and Complementary
      Medicine database (AMED) (1985 to October 2010), Cumulative Index to Nursing and
      Allied Health (CINAHL) (1982 to October 2010), Proquest Digital Dissertations
      (1861 to October 2010), and Psychological Database for Brain Impairment Treatment
      Efficacy (PsycBITE) (2004 to October 2010). In an effort to identify further
      published, unpublished and ongoing trials, we searched trial registries and major
      international stroke conference proceedings, scanned reference lists, and
      contacted select individuals known to the review team who are actively involved
      in psychological aspects of stroke research, and the Association of the British
      Pharmaceutical Industry. SELECTION CRITERIA: Two review authors independently
      screened and selected titles and abstracts for inclusion in the review.
      Randomised trials of any intervention in patients with stroke where the treatment
      of anxiety was an outcome were eligible. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data for analysis. We performed a narrative
      review. A meta-analysis was planned but not carried out as studies were not of
      sufficient quality to warrant doing so. MAIN RESULTS: We included two trials
      (three interventions) involving 175 participants with co-morbid anxiety and
      depression in the review. Both trials used the Hamilton Anxiety Scale (HAM-A) to
      assess anxiety, and neither included a placebo control group. One trial
      randomised 81 patients to paroxetine, paroxetine plus psychotherapy or standard
      care. Mean level of anxiety severity scores were 58% and 71% lower in the
      paroxetine, and paroxetine plus psychotherapy groups respectively compared with
      those in standard care at follow-up (P < 0.01). The second trial randomised 94
      stroke patients, also with co-morbid anxiety and depression, to receive buspirone
      hydrochloride or standard care. At follow-up, the mean level of anxiety was
      significantly lower for those receiving buspirone relative to controls (P <
      0.01). Half of the participants receiving paroxetine experienced adverse events
      that included nausea, vomiting or dizziness; however, only 14% of those receiving
      buspirone experienced nausea or palpitations. No information was provided about
      the duration of symptoms associated with adverse events. AUTHORS' CONCLUSIONS:
      There is insufficient evidence to guide the treatment of anxiety after stroke.
      The data available suggest that pharmaceutical therapy (paroxetine and buspirone)
      may be effective in reducing anxiety symptoms in stroke patients with co-morbid
      anxiety and depression. No information was available for stroke patients with
      anxiety only. Randomised placebo controlled trials are needed.

PMID- 22161440
TI  - Patient education in the management of coronary heart disease.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is a complex multifaceted intervention
      consisting of three core modalities: education, exercise training and
      psychological support. Whilst exercise and psychological interventions for
      patients with coronary heart disease (CHD) have been the subject of Cochrane
      systematic reviews, the specific impact of the educational component of CR has
      not previously been investigated. OBJECTIVES: 1. Assess effects of patient
      education on mortality, morbidity, health-related quality of life (HRQofL) and
      healthcare costs in patients with CHD.2. Explore study level predictors of the
      effects of patient education (e.g. individual versus group intervention, timing
      with respect to index cardiac event). SEARCH METHODS: The following databases
      were searched: The Cochrane Library, (CENTRAL, CDSR, DARE, HTA, NHSEED), MEDLINE
      (OVID), EMBASE (OVID), PsycINFO (EBSCOhost) and CINAHL (EBSCOhost). Previous
      systematic reviews and reference lists of included studies were also searched. No
      language restrictions were applied. SELECTION CRITERIA: 1. Randomised controlled
      trials (RCTs) where the primary interventional intent was education.2. Studies
      with a minimum of six-months follow-up and published in 1990 or later.3. Adults
      with diagnosis of CHD. DATA COLLECTION AND ANALYSIS: Two review authors selected
      studies and extracted data. Attempts were made to contact all study authors to
      obtain relevant information not available in the published manuscript. For
      dichotomous variables, risk ratios and 95% confidence intervals (CI) were derived
      for each outcome. For continuous variables, mean differences and 95% CI were
      calculated for each outcome. MAIN RESULTS: Thirteen RCTs involving 68,556
      subjects with CHD and follow-up from six to 60 months were found. Overall,
      methodological quality of included studies was moderate to good. Educational
      'dose' ranged from a total of two clinic visits to a four-week residential stay
      with 11 months of follow-up sessions. Control groups typically received usual
      medical care. There was no strong evidence of an effect of education on all-cause
      mortality (Relative Risk (RR): 0.79, 95% CI 0.55 to 1.13), cardiac morbidity
      (subsequent myocardial infarction RR: 0.63, 95% CI 0.26 to 1.48,
      revascularisation RR: 0.58, 95% CI 0.19 to 1.71) or hospitalisation (RR: 0.83,
      95% CI:0.65 to 1.07). Whilst some HRQofL domain scores were higher with
      education, there was no consistent evidence of superiority across all domains.
      Different currencies and years studies were performed making direct comparison of
      healthcare costs challenging, although there is evidence to suggest education may
      be cost-saving by reducing subsequent healthcare utilisation.This review had
      insufficient power to exclude clinically important effects of education on
      mortality and morbidity of patients with CHD. AUTHORS' CONCLUSIONS: We did not
      find strong evidence that education reduced all cause mortality, cardiac
      morbidity, revascularisation or hospitalisation compared to control. There was
      some evidence to suggest that education may improve HRQofL and reduce overall
      healthcare costs. Whilst our findings are generally supportive of current
      guidelines that CR should include not only exercise and psychological
      interventions, further research into education is needed.

PMID- 22161441
TI  - Eslicarbazepine acetate add-on for drug-resistant partial epilepsy.
AB  - BACKGROUND: The majority of people with epilepsy will have a good prognosis, but
      up to 30% of patients will continue to have seizures despite several regimens of
      antiepileptic drugs. In this review we summarized the current evidence regarding
      eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant
      partial epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of ESL
      when used as an add-on treatment for people with drug-resistant partial epilepsy.
      SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (3
      November 2011), The Cochrane Central Register of Controlled Trials (CENTRAL issue
      4 of 4, The Cochrane Library 2011), and MEDLINE (1948 to October week 4, 2011).
      There were no language restrictions. We reviewed the reference lists of retrieved
      studies to search for additional reports of relevant studies. We also contacted
      the manufacturers of ESL and experts in the field for information about any
      unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo controlled
      double-blind add-on trials of ESL in people with drug-resistant partial epilepsy.
      DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials
      for inclusion and extracted data. Outcomes investigated included 50% or greater
      reduction in seizure frequency; seizure freedom; treatment withdrawal; adverse
      effects; and drug interactions. Primary analyses were by intention to treat. The
      dose response relationship was evaluated in regression models. MAIN RESULTS: Four
      trials (1146 participants) were included; all studies were funded by BIAL. The
      overall relative risk (RR) with 95% confidence interval (CIs) for 50% or greater
      reduction in seizure frequency outcome was 1.86 (95% CI 1.46 to 2.36). Dose
      regression analysis showed evidence that ESL reduced seizure frequency with an
      increase in efficacy with increasing doses of ESL. ESL was significantly
      associated with seizure freedom (RR 3.04, 95% CI 1.44 to 6.42). Participants
      seemed more likely (albeit not significantly) to have ESL withdrawn for adverse
      effects (RR 2.26, 95% CI 0.98 to 5.21) but not for any reason (RR 1.07, 95% CI
      0.73 to 1.57). The following adverse effects were significantly associated with
      ESL: dizziness (RR 3.09, 99% CI 1.76 to 5.43); nausea (RR 3.06, 99% CI 1.07 to
      8.74); and diplopia (RR 3.73, 99% CI 1.19 to 11.64). AUTHORS' CONCLUSIONS:
      Eslicarbazepine acetate reduces seizure frequency when used as an add-on
      treatment for people with drug-resistant partial epilepsy. The trials included in
      this review were of short-term duration and focused on adults.

PMID- 22161442
TI  - Interventions for the management of dry mouth: topical therapies.
AB  - BACKGROUND: Xerostomia (the feeling of dry mouth) is a common symptom especially
      in older adults. Causes of dry mouth include medications, autoimmune disease
      (Sjogren's Syndrome), radiotherapy or chemotherapy for cancer, hormone disorders
      and infections. OBJECTIVES: To determine which topical treatments for dry mouth
      are effective in reducing this symptom. SEARCH METHODS: We searched the following
      electronic databases: the Cochrane Oral Health Group Trials Register (28 October
      2011), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library, Issue 4 2011), MEDLINE via OVID (1950 to 28 October 2011), EMBASE via
      OVID (1980 to 28 October 2011), CINAHL via EBSCO (1980 to 28 October 2011), AMED
      via OVID (1985 to 28 October 2011), CANCERLIT via PubMed (1950 to 28 October
      2011). SELECTION CRITERIA: We included randomised controlled trials of topical
      interventions such as lozenges, sprays, mouthrinses, gels, oils, chewing gum or
      toothpastes for the treatment of dry mouth symptom. We classified interventions
      into two broad categories, saliva stimulants and saliva substitutes, and these
      were compared with either placebo or another intervention. We included both
      parallel group and crossover trials. DATA COLLECTION AND ANALYSIS: Two or more
      review authors independently carried out data extraction and assessed risk of
      bias. Trial authors were contacted for additional information as required. MAIN
      RESULTS: Thirty-six randomised controlled trials involving 1597 participants met
      the inclusion criteria. Two trials compared saliva stimulants to placebo, nine
      trials compared saliva substitutes to placebo, five trials compared saliva
      stimulants directly with saliva substitutes, 18 trials directly compared two or
      more saliva substitutes, and two trials directly compared two or more saliva
      stimulants. Only one trial was at low risk of bias and 17 were at high risk of
      bias. Due to the range of interventions, comparisons and outcome measures in the
      trials, meta-analysis was possible for only a few comparisons. Oxygenated
      glycerol triester (OGT) saliva substitute spray shows evidence of effectiveness
      compared to an electrolyte spray (standardised mean difference (SMD) 0.77, 95%
      confidence interval (CI) 0.38 to 1.15) which corresponds to approximately a mean
      difference of 2 points on a 10-point visual analogue scale (VAS) for mouth
      dryness. Both integrated mouthcare systems (toothpaste + gel + mouthwash) and
      oral reservoir devices show promising results but there is insufficient evidence
      at present to recommend their use. Although chewing gum is associated with
      increased saliva production in the majority of those with residual capacity,
      there is no evidence that gum is more or less effective than saliva substitutes.
      AUTHORS' CONCLUSIONS: There is no strong evidence from this review that any
      topical therapy is effective for relieving the symptom of dry mouth. OGT spray is
      more effective than an aqueous electrolyte spray (SMD 0.77, 95% CI 0.38 to 1.15)
      which is approximately equivalent to a mean difference of 2 points on a 10-point
      VAS scale for mouth dryness. Chewing gums appear to increase saliva production in
      those with residual secretory capacity and may be preferred by patients, but
      there is no evidence that gum is better or worse than saliva substitutes.
      Integrated mouthcare systems and oral reservoir devices may be helpful but
      further research is required to confirm this. Well designed, adequately powered
      randomised controlled trials of topical interventions for dry mouth, which are
      designed and reported according to CONSORT guidelines, are required to provide
      evidence to guide clinical care. For many people the symptom of dry mouth is a
      chronic problem and trials should evaluate whether treatments are palatable,
      effective in reducing xerostomia, as well as the long-term effects of treatments
      on quality of life of those with chronic dry mouth symptoms.

PMID- 22161443
TI  - Methods to decrease blood loss and transfusion requirements for liver
      transplantation.
AB  - BACKGROUND: Excessive blood loss and increased blood transfusion requirements may
      have significant impact on the short-term and long-term outcomes after liver
      transplantation. OBJECTIVES: To compare the potential benefits and harms of
      different methods of decreasing blood loss and blood transfusion requirements
      during liver transplantation. SEARCH METHODS: We searched The Cochrane Central
      Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, Science
      Citation Index Expanded, and metaRegister of Controlled Trials until September
      2011. SELECTION CRITERIA: We included all randomised clinical trials that were
      performed to compare various methods of decreasing blood loss and blood
      transfusion requirements during liver transplantation. DATA COLLECTION AND
      ANALYSIS: Two authors independently identified the trials and extracted the data.
      We analysed the data with both the fixed-effect and the random-effects model
      using RevMan Analysis. For each outcome we calculated the risk ratio (RR), mean
      difference (MD), or standardised mean difference (SMD) with 95% confidence
      intervals (CI) based on available data analysis. We also conducted network meta
      analysis. MAIN RESULTS: We included 33 trials involving 1913 patients. The sample
      size in the trials varied from 8 to 209 participants. The interventions included
      pharmacological interventions (aprotinin, tranexamic acid, epsilon amino caproic
      acid, antithrombin 3, recombinant factor (rFvIIa), oestrogen, prostaglandin,
      epinephrine), blood substitutes (blood components rather than whole blood,
      hydroxy-ethyl starch, thromboelastography), and cardiovascular interventions (low
      central venous pressure). All the trials were of high risk of bias. Primary
      outcomes were reported in at least two trials for the following comparisons:
      aprotinin versus control, tranexamic acid versus control, recombinant factor VIIa
      (rFVIIa) versus control, and tranexamic acid versus aprotinin. There were no
      significant differences in the 60-day mortality (3 trials; 6/161 (3.7%) in the
      aprotinin group versus 8/119 (6.7%) in the control group; RR 0.52; 95% CI 0.18 to
      1.45), primary graft non-function (2 trials; 0/128 (0.0%) in the aprotinin group
      versus 4/89 (4.5%) in the control group; RR 0.15; 95% CI 0.02 to 1.25),
      retransplantation (3 trials; 2/256 (0.8%) in the aprotinin group versus 12/178
      (6.7%) in the control group; RR 0.21; 95% CI 0.02 to 1.79), or thromboembolic
      episodes (3 trials; 4/161 (2.5%) in the aprotinin group versus 5/119 (4.2%) in
      the control group; RR 0.59; 95% CI 0.19 to 1.84) between the aprotinin and
      control groups. There were no significant differences in the 60-day mortality (3
      trials; 4/83 (4.8%) in the tranexamic acid group versus 5/56 (8.9%) in the
      control group; RR 0.55; 95% CI 0.17 to 1.76), retransplantation (2 trials; 3/41
      (7.3%) in the tranexamic acid group versus 3/36 (8.3%) in the control group; RR
      0.79; 95% CI 0.18 to 3.48), or thromboembolic episodes (5 trials; 5/103 (4.9%) in
      the tranexamic acid group versus 1/76 (1.3%) in the control group; RR 2.20; 95%
      CI 0.38 to 12.64) between the tranexamic acid and control groups. There were no
      significant differences in the 60-day mortality (3 trials; 8/195 (4.1%) in the
      recombinant factor VIIa (rFVIIa) group versus 2/91 (2.2%) in the control group;
      RR 1.51; 95% CI 0.33 to 6.95), thromboembolic episodes (2 trials; 24/185 (13.0%)
      in the rFVIIa group versus 8/81 (9.9%) in the control group; RR 1.38; 95% CI 0.65
      to 2.91), or serious adverse events (2 trials; 90/185 (48.6%) in the rFVIIa group
      versus 30/81 (37.0%) in the control group; RR 1.30; 95% CI 0.94 to 1.78) between
      the rFVIIa and control groups. There were no significant differences in the 60
      day mortality (2 trials; 6/91 (6.6%) in the tranexamic acid group versus 1/87
      (1.1%) in the aprotinin group; RR 4.12; 95% CI 0.71 to 23.76) or thromboembolic
      episodes (2 trials; 4/91 (4.4%) in the tranexamic acid group versus 2/87 (2.3%)
      in the aprotinin group; RR 1.97; 95% CI 0.37 to 10.37) between the tranexamic
      acid and aprotinin groups. The remaining outcomes in the above comparisons and
      the remaining comparisons included only only trial under the primary outcome or
      the outcome was not reported at all in the trials. There were no significant
      differences in the mortality, primary graft non-function, graft failure,
      retransplantation, thromboembolic episodes, or serious adverse events in any of
      these comparisons. However, the confidence intervals were wide, and it is not
      possible to reach any conclusion on the safety of the interventions. None of the
      trials reported the quality of life in patients.Secondary outcomes were reported
      in at least two trials for the following comparisons - aprotinin versus control,
      tranexamic acid versus control, rFVIIa versus control, thromboelastography versus
      control, and tranexamic acid versus aprotinin. There was significantly lower
      allogeneic blood transfusion requirements in the aprotinin group than the control
      group (8 trials; 185 patients in aprotinin group and 190 patients in control
      group; SMD -0.61; 95% CI -0.82 to -0.40). There were no significant differences
      in the allogeneic blood transfusion requirements between the tranexamic acid and
      control groups (4 trials; 93 patients in tranexamic acid group and 66 patients in
      control group; SMD -0.27; 95% CI -0.59 to 0.06); rFVIIa and control groups (2
      trials; 141 patients in rFVIIa group and 80 patients in control group; SMD -0.05;
      95% CI -0.32 to 0.23); thromboelastography and control groups (2 trials; 31
      patients in thromboelastography group and 31 patients in control group; SMD 
      0.73; 95% CI -1.69 to 0.24); or between the tranexamic acid and aprotinin groups
      (3 trials; 101 patients in tranexamic acid group and 97 patients in aprotinin
      group; SMD -0.09; 95% CI -0.36 to 0.19). The remaining outcomes in the above
      comparisons and the remaining comparisons included only only trial under the
      primary outcome or the outcome was not reported at all in the trials. There were
      no significant differences in the blood loss, transfusion requirements, hospital
      stay, or intensive care unit stay in most of the comparisons. AUTHORS'
      CONCLUSIONS: Aprotinin, recombinant factor VIIa, and thromboelastography groups
      may potentially reduce blood loss and transfusion requirements. However, risks of
      systematic errors (bias) and risks of random errors (play of chance) hamper the
      confidence in this conclusion. We need further well-designed randomised trials
      with low risk of systematic error and low risk of random errors before these
      interventions can be supported or refuted.

PMID- 22161445
TI  - Rituximab for relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: More than 80% of individuals with multiple sclerosis (MS) experience
      a relapsing-remitting disease course. Approximately ten years after disease
      onset, an estimated 50% of individuals with relapsing-remitting MS (RR-MS)
      convert to secondary progressive MS. Quality of life is considerably impaired in
      early RR-MS. The increased costs are associated with relapse occurrence and
      increasing disease severity. Pharmaceutical interventions aimed at delaying the
      progression of disease may help to reduce the economic burden of MS. It has been
      showed that B lymphocytes involve in the pathophysiology of MS and rituximab
      lyses B cells via complement and antibody-dependent cellular cytotoxicity.
      Current clinical trials are evaluating the role of rituximab as a B-cell-targeted
      therapy in the treatment of RR-MS. OBJECTIVES: The effectiveness and safety of
      rituximab alone or as add-on, versus placebo or other treatments for RR-MS were
      assessed. SEARCH METHODS: The Trials Search Co-ordinator searched the Cochrane
      Multiple Sclerosis Group's Specialised Register (3 March 2011). We checked
      references in identified trials and manually searched the reports (2004 to May
      2011) from neurological associations and MS Societies in Europe and America. We
      also communicated with researchers who were participating in trials on rituximab
      and contacted Genentech, BiogenIdec, Roche. SELECTION CRITERIA: All randomised
      double-blind controlled parallel clinical trials with a length of follow-up >=
      one year, evaluating rituximab, alone or as add-on with other therapies, versus
      placebo, or any other treatment for patients with RR-MS, without restrictions
      regarding dosage, administration frequency and duration of treatment. Titles and
      abstracts of the citations retrieved by the literature search were screened
      independently for inclusion/exclusion by two review authors. Any disagreement
      regarding inclusion was resolved by discussion, or by referral to a third
      assessor if necessary. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. Disagreements were
      discussed and resolved by consensus among review authors. Principal investigators
      of included studies were contacted for additional data or confirmation. MAIN
      RESULTS: One trial involving 104 adult RR MS patients with an entry score <= 5.0
      EDSS and at least one relapse during the preceding year was included. This trial
      evaluated rituximab alone versus placebo with a single course of rituximab (on
      day 1 and 15). Treated patients had a lower rate of relapse at 24 weeks but not
      at 48 weeks. The MRI data were available only at 24 weeks. A significant
      attrition bias was found at 48 week (40.0% in the placebo group and 15.9% in the
      rituximab group). Mild-to-moderate infusion-associated adverse events within 24
      hours after the first rituximab infusion occurred in the rituximab group.
      AUTHORS' CONCLUSIONS: We are unable to give any clear recommendations for the use
      of rituximab as a therapy for RR-MS. The beneficial effects of rituximab for RR
      MS remain inconclusive because of the high attrition bias, the small number of
      participants and the short follow-up. However, short-term treatment with a single
      course of rituximab resulted to be safe for most patients with RR-MS. The
      potential benefits of rituximab for treating RR-MS need to be evaluated in large
      scale studies along with long-term safety. Disability progression and quality of
      life should be addressed in future research.

PMID- 22161446
TI  - Bisphosphonates for osteoporosis in primary biliary cirrhosis.
AB  - BACKGROUND: Bisphosphonates are widely used for treatment of postmenopausal
      osteoporosis. Patients with primary biliary cirrhosis often have osteoporosis -
      either postmenopausal or secondary to the liver disease. No systematic review or
      meta-analysis has assessed the effects of bisphosphonates for osteoporosis in
      patients with primary biliary cirrhosis. OBJECTIVES: To assess the beneficial and
      harmful effects of bisphosphonates for osteoporosis in primary biliary cirrhosis.
      SEARCH METHODS: The Cochrane Hepato-Biliary Group Controlled Trials Register, The
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library,
      MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, clinicaltrials.gov, the
      WHO International Clinical Trials Registry Platform, and full text searches were
      conducted until November 2011. Manufacturers and authors were contacted for
      additional studies during the conductance of the review. SELECTION CRITERIA: All
      randomised clinical trials of bisphosphonates in primary biliary cirrhosis
      compared with placebo or no intervention, or another bisphosphonate, or any other
      drug. DATA COLLECTION AND ANALYSIS: Two authors extracted data. RevMan Analysis
      was used for statistical analysis of dichotomous data with risk ratio (RR) or
      risk difference (RD) and of continuous data with mean difference (MD) or
      standardised mean difference (SMD), all with 95% confidence intervals (CI).
      Methodological components were used to assess risk of systematic errors (bias).
      Trial sequential analysis was also used to control for random errors (play of
      chance). MAIN RESULTS: Six trials were included. Three trials with 106
      participants, of which two trials with high risk of bias, did not demonstrate
      significant effects of bisphosphonates (etidronate or alendronate) versus placebo
      or no intervention regarding mortality (RD 0.00; 95% CI -0.12 to 0.12, I2 = 0%),
      fractures (RR 0.87; 95% CI 0.29 to 2.66, I2 = 0%), or adverse events (RR 1.00;
      95% CI 0.49 to 2.04). Two trials with 62 participants with high risk of bias
      compared one bisphosphonate (etidronate or alendronate) versus another
      (alendronate or ibandronate) and found no significant difference regarding
      mortality (RD -0.03; 95% CI -0.14 to 0.07, I2 = 0%), fractures (RR 0.95; 95% CI
      0.18 to 5.06, I2 = 0%), or adverse events (RR 1.00; 95% CI 0.49 to 2.04, I2 =
      0%). Bisphosphonates had no significant effect on liver-related mortality, liver
      transplantation, or liver-related morbidity compared with placebo or no
      intervention, or another bisphosphonate. Bisphosphonates had no significant
      effect on bone mineral density compared with placebo or no intervention, or
      another bisphosphonate. Bisphosphonates compared with placebo or no intervention
      seem to decrease the urinary amino telopeptides of collagen I (NTx) concentration
      (MD -16.93 nmol bone collagen equivalents/mmol creatinine; 95% CI -23.77 to 
      10.10; 2 trials with 88 patients; I2 = 0%) and serum osteocalcin (SMD -0.81; 95%
      CI -1.22 to -0.39; 3 trials with 100 patients; I2 = 34 %) concentration. The
      former result was supported by trial sequential analysis, but not the latter.
      Alendronate compared with another bisphosphonate (ibandronate) had no significant
      effect on serum osteocalcin concentration (MD -3.61 ng/ml, 95% CI -9.41 to 2.18;
      2 trials with 47 patients; I2 = 82%) in a random-effects meta-analysis, but it
      significantly decreased serum osteocalcin (MD -4.40 ng/ml, 95% CI -6.75 to -2.05;
      2 trials with 47 patients; I2 = 82%), the procollagen type I N-terminal
      propeptide (MD -8.79 ng/ml, 95% CI -15.96 to -1.63; 2 trials with 47 patients; I2
      = 38%), and NTx concentration (MD -14.07 nmol bone collagen equivalents/mmol
      creatinine, 95% CI -24.23 to -3.90; 2 trials with 46 patients; I2=0%) in a fixed
      effect model. The latter two results were not supported by trial sequential
      analyses. There was no statistically significant difference in the number of
      patients having bisphosphonates withdrawn due to adverse events compared with
      placebo or no intervention (RD -0.04; 95% CI -0.21 to 0.12; 2 trials with 46
      patients; I2 = 0%), or another bisphosphonate (RR 0.56; 95% CI 0.14 to 2.17; 2
      trials with 62 patients; I2 = 0%). One trial with 32 participants and with high
      risk of bias compared etidronate versus sodium fluoride without finding
      significant difference regarding mortality, fractures, adverse events, or bone
      mineral density. Etidronate compared with sodium fluoride significantly decreased
      serum osteocalcin, urinary hydroxyproline, and parathyroid hormone concentration.
      AUTHORS' CONCLUSIONS: We did not find evidence to support or refute the use of
      bisphosphonates for patients with primary biliary cirrhosis. The data seem to
      indicate a possible positive intervention effect of bisphosphonates on decreasing
      urinary amino telopeptides of collagen I concentration compared with placebo or
      no intervention with no risk of random error. There is need for more randomised
      clinical trials assessing the effects of bisphosphonates for osteoporosis on
      patient-relevant outcomes in primary biliary cirrhosis.

PMID- 22161444
TI  - Intermittent iron supplementation for improving nutrition and development in
      children under 12 years of age.
AB  - BACKGROUND: Approximately 600 million children of preschool and school age are
      anaemic worldwide. It is estimated that half of the cases are due to iron
      deficiency. Consequences of iron deficiency anaemia during childhood include
      growth retardation, reduced school achievement, impaired motor and cognitive
      development, and increased morbidity and mortality. The provision of daily iron
      supplements is a widely used strategy for improving iron status in children but
      its effectiveness has been limited due to its side effects, which can include
      nausea, constipation or staining of the teeth. As a consequence, intermittent
      iron supplementation (one, two or three times a week on non-consecutive days) has
      been proposed as an effective and safer alternative to daily supplementation.
      OBJECTIVES: To assess the effects of intermittent iron supplementation, alone or
      in combination with other vitamins and minerals, on nutritional and developmental
      outcomes in children from birth to 12 years of age compared with a placebo, no
      intervention or daily supplementation. SEARCH METHODS: We searched the following
      databases on 24 May 2011: CENTRAL (2011, Issue 2), MEDLINE (1948 to May week 2,
      2011), EMBASE (1980 to 2011 Week 20), CINAHL (1937 to current), POPLINE (all
      available years) and WHO International Clinical Trials Registry Platform (ICTRP).
      On 29 June 2011 we searched all available years in the following databases:
      SCIELO, LILACS, IBECS and IMBIOMED. We also contacted relevant organisations (on
      3 July 2011) to identify ongoing and unpublished studies. SELECTION CRITERIA:
      Randomised and quasi-randomised trials with either individual or cluster
      randomisation. Participants were children under the age of 12 years at the time
      of intervention with no specific health problems. The intervention assessed was
      intermittent iron supplementation compared with a placebo, no intervention or
      daily supplementation. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed the eligibility of studies against the inclusion criteria, extracted
      data from included studies and assessed the risk of bias of the included studies.
      MAIN RESULTS: We included 33 trials, involving 13,114 children (~49% females)
      from 20 countries in Latin America, Africa and Asia. The methodological quality
      of the trials was mixed.Nineteen trials evaluated intermittent iron
      supplementation versus no intervention or a placebo and 21 studies evaluated
      intermittent versus daily iron supplementation. Some of these trials contributed
      data to both comparisons. Iron alone was provided in most of the trials.Fifteen
      studies included children younger than 60 months; 11 trials included children 60
      months and older, and seven studies included children in both age categories. One
      trial included exclusively females. Seven trials included only anaemic children;
      three studies assessed only non-anaemic children, and in the rest the baseline
      prevalence of anaemia ranged from 15% to 90%.In comparison with receiving no
      intervention or a placebo, children receiving iron supplements intermittently
      have a lower risk of anaemia (average risk ratio (RR) 0.51, 95% confidence
      interval (CI) 0.37 to 0.72, ten studies) and iron deficiency (RR 0.24, 95% CI
      0.06 to 0.91, three studies) and have higher haemoglobin (mean difference (MD)
      5.20 g/L, 95% CI 2.51 to 7.88, 19 studies) and ferritin concentrations (MD 14.17
      ug/L, 95% CI 3.53 to 24.81, five studies).Intermittent supplementation was as
      effective as daily supplementation in improving haemoglobin (MD -0.60 g/L, 95% CI
      -1.54 to 0.35, 19 studies) and ferritin concentrations (MD -4.19 ug/L, 95% CI 
      9.42 to 1.05, 10 studies), but increased the risk of anaemia in comparison with
      daily iron supplementation (RR 1.23, 95% CI 1.04 to1.47, six studies). Data on
      adherence were scarce and it tended to be higher among those children receiving
      intermittent supplementation, although this result was not statistically
      significant.We did not identify any differential effect of the type of
      intermittent supplementation regimen (one, two or three times a week), the total
      weekly dose of elemental iron, the nutrient composition, whether recipients were
      male or female or the length of the intervention. AUTHORS' CONCLUSIONS:
      Intermittent iron supplementation is efficacious to improve haemoglobin
      concentrations and reduce the risk of having anaemia or iron deficiency in
      children younger than 12 years of age when compared with a placebo or no
      intervention, but it is less effective than daily supplementation to prevent or
      control anaemia. Intermittent supplementation may be a viable public health
      intervention in settings where daily supplementation has failed or has not been
      implemented. Information on mortality, morbidity, developmental outcomes and side
      effects, however, is still lacking.

PMID- 22161447
TI  - Hormone replacement for osteoporosis in women with primary biliary cirrhosis.
AB  - BACKGROUND: Women with primary biliary cirrhosis often suffer from postmenopausal
      osteoporosis due to their age, or osteoporosis secondary to their liver disease,
      or treatments provided for their liver disease. Hormone replacement increases
      bone mineral density and reduces fractures in postmenopausal women. On the other
      hand, hormone replacement increases the risk of various adverse events. We could
      not identify any meta-analyses or systematic reviews on hormone replacement in
      women with primary biliary cirrhosis. OBJECTIVES: To assess the beneficial and
      harmful effects of hormone replacement for osteoporosis in women with primary
      biliary cirrhosis. SEARCH METHODS: The Cochrane Hepato-Biliary Group Controlled
      Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in
      The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS,
      clinicaltrials.gov, the WHO International Clinical Trials Registry Platform, and
      full text searches were conducted until November 2011. Manufacturers and authors
      were contacted during the review conductance. SELECTION CRITERIA: All randomised
      clinical trials of hormone replacement in primary biliary cirrhosis administered
      by any route, or regimen, or dose compared with placebo or no intervention. DATA
      COLLECTION AND ANALYSIS: Two authors extracted data. RevMan Analysis was used for
      statistical analysis of dichotomous data with risk ratio (RR) or risk difference
      (RD) and of continuous data with mean difference (MD), all with 95% confidence
      intervals (CI). Methodological domains were used to assess risk of systematic
      errors (bias). Trial sequential analysis was used to control for random errors
      (play of chance). MAIN RESULTS: Two trials with 49 participants were included.
      One trial had low risk of bias. The other trial had high risk of bias. Hormone
      replacement had no effect on all-cause mortality (RD 0.00; 95% CI -0.11 to 0.11,
      I2 = 0%) and fractures (RD -0.08; 95% CI -0.24 to 0.07, I2 = 0%). Hormone
      replacement significantly increased adverse events and number of patients having
      hormone replacement withdrawn due to adverse events (RR 5.26; 95% CI 1.26 to
      22.04, I2 = 0%). Hormone replacement had no significant effect on lumbar spine
      bone mineral density (MD 1.25 g/cm2 year?1; 95% CI -0.91 to 3.42, I2 = 0%). On
      the other hand, a significant increase in proximal femur bone mineral density was
      observed in the control group (MD 2.24 g/cm2 year?1; 95% CI 0.74 to 3.74, I2 =
      0%). Hormone replacement had no significant effect on liver-related mortality,
      liver transplantation, or liver-related morbidity. Hormone replacement had no
      significant effect on serum bilirubin concentration (MD 4.60 umol/L; 95% CI -3.42
      to 12.62, I2 = 0%). AUTHORS' CONCLUSIONS: We did not find evidence to support the
      use of hormone replacement for women with primary biliary cirrhosis. It seems
      that hormone replacement is connected with a significant increase in the
      occurrence of adverse events.

PMID- 22161448
TI  - Intermittent iron supplementation for reducing anaemia and its associated
      impairments in menstruating women.
AB  - BACKGROUND: Daily iron supplementation has been traditionally a standard practice
      for preventing and treating anaemia but its long term use has been limited as it
      has been associated with adverse side effects such as nausea, constipation and
      teeth staining. Intermittent iron supplementation has been suggested as an
      effective and safer alternative to daily iron supplementation for preventing and
      reducing anaemia at population level, especially in areas where this condition is
      highly prevalent. OBJECTIVES: To assess the effects of intermittent oral iron
      supplementation, alone or in combination with other nutrients, on anaemia and its
      associated impairments in menstruating women, compared with no intervention, a
      placebo or daily supplementation. SEARCH METHODS: We searched the following
      databases in May 2011: CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE
      (1948 to May Week 3, 2011), EMBASE (1980 to 2011 Week 20), CINAHL (1937 to
      current), POPLINE (all available years), Science Citation Index (1970 to 27 May
      2011), BIOSIS Previews (1969 to current), and CPCI-S (1990 to 27 May 2011). On 7
      July 2011 we searched all available years in the following databases: SCIELO,
      LILACS, IBECS and IMBIOMED, the Networked Digital Library of Theses and
      Dissertations, metaRegister and the WHO International Clinical Trials Registry
      Platform (ICTRP). We also contacted relevant organisations (on 11 October 2011)
      to identify ongoing and unpublished studies. SELECTION CRITERIA: Randomised and
      quasi-randomised trials with either individual or cluster randomisation.
      Participants were menstruating women, that is women beyond menarche and prior to
      menopause who were not pregnant or lactating and did not have a known condition
      that impeded the presence of menstrual periods. The intervention was the use of
      iron supplements intermittently (one, two or three times a week on non
      consecutive days) compared with no intervention, a placebo, or the use of same
      supplements on a daily basis. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the eligibility of studies against the inclusion criteria,
      extracted data from included studies, checked data entry for accuracy and
      assessed the risk of bias of the included studies. MAIN RESULTS: We included 21
      trials involving 10,258 women. Although the quality across trials was variable,
      the results consistently show that in comparison with no intervention or a
      placebo, intermittent iron supplementation (alone or with any other vitamins and
      minerals) reduces the risk of having anaemia (RR 0.73; 95% CI 0.56 to 0.95, 10
      trials) and improves the concentration of haemoglobin (MD 4.58 g/L; 95% CI 2.56
      to 6.59, 13 trials) and ferritin (MD 8.32 MUg/L; 95% CI 4.97 to 11.66, six
      trials). However, in comparison with daily supplementation, women receiving
      supplements intermittently presented anaemia more frequently (RR 1.26; 95% CI
      1.04 to 1.51, six trials), despite achieving similar haemoglobin concentrations
      on average (MD -0.15 g/L; 95% CI -2.20 to 1.91, eight trials).Information on
      disease outcomes, adherence, side effects, economic productivity and work
      performance is scarce and the evidence about the effects of intermittent
      supplementation on them is unclear.Overall, whether the supplements were given
      once or twice weekly, for less or more than three months, contained less or more
      than 60 mg of elemental iron per week, or to populations with different degrees
      of anaemia at baseline did not seem to affect the findings. Furthermore, the
      response did not differ in areas where malaria is frequent, although very few
      trials were conducted in these settings. AUTHORS' CONCLUSIONS: Intermittent iron
      supplementation in menstruating women is a feasible intervention in settings
      where daily supplementation is likely to be unsuccessful or not possible. In
      comparison with daily supplementation, the provision of iron supplements
      intermittently is less effective in preventing or controlling anaemia. More
      information is needed on morbidity (including malaria outcomes), side effects,
      work performance, economic productivity, depression and adherence to the
      intervention.

PMID- 22161449
TI  - Treadmill interventions with partial body weight support in children under six
      years of age at risk of neuromotor delay.
AB  - BACKGROUND: Delayed motor development may occur in children with Down syndrome,
      cerebral palsy or children born preterm, which in turn may limit the child's
      opportunities to explore the environment. Neurophysiologic and early intervention
      literature suggests that task-specific training facilitates motor development.
      Treadmill intervention is a good example of locomotor task-specific training.
      OBJECTIVES: To assess the effectiveness of treadmill intervention on locomotor
      motor development in pre-ambulatory infants and children under six years of age
      who are at risk for neuromotor delay. SEARCH METHODS: In March 2011 we searched
      CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE (1948 to March Week 2,
      2011), EMBASE (1980 to Week 11, 2011), PsycINFO (1887 to current), CINAHL (1937
      to current), Science Citation Index (1970 to 19 March 2011), PEDro (until 7 March
      2011), CPCI-S (1990 to 19 March 2011) and LILACS (until March 2011). We also
      searched ICTRP, ClinicalTrials.gov, mRCT and CenterWatch. SELECTION CRITERIA: We
      included randomised controlled trials, quasi-randomised controlled trials and
      controlled clinical trials that evaluated the effect of treadmill intervention in
      children up to six years of age with delays in gait development or the attainment
      of independent walking or who were at risk of neuromotor delay. DATA COLLECTION
      AND ANALYSIS: Four authors independently extracted the data using standardised
      forms. Outcome parameters were structured according to the "Body functions" and
      "Activity and Participation" components of the International Classification of
      Functioning, Disability and Health, Children & Youth version (ICFCY), which was
      developed by the World Health Organization. MAIN RESULTS: We included five
      studies, which reported on treadmill intervention in 139 children. Of the 139
      children, 73 were allocated to treadmill intervention groups, with the other
      children serving as controls. The studies varied in the type of population
      studied (children with Down syndrome, cerebral palsy or who were at risk for
      neuromotor delay); the type of comparison (for example, treadmill versus no
      intervention, high intensity treadmill versus low intensity); the time of
      evaluation (during the intervention or at various intervals after intervention),
      and the parameters assessed. Due to the diversity of the studies, we were only
      able to use data from three studies in meta-analyses and these were limited to
      two outcomes: age of onset of independent walking and gross motor
      function.Evidence suggested that treadmill intervention could lead to earlier
      onset of independent walking when compared to no treadmill intervention (two
      studies; effect estimate -1.47; 95% confidence interval (CI): -2.97, 0.03),
      though these trials studied two different populations and children with Down
      syndrome seemed to benefit while it was not clear if this was the case for
      children at high risk of neuromotor disabilities. Another two studies, both in
      children with Down syndrome, compared different types of treadmill intervention:
      one compared treadmill intervention with and without orthotics, while the other
      compared high versus low intensity treadmill intervention. Both were inconclusive
      regarding the impact of these different protocols on the age at which children
      started to walk.There is insufficient evidence to determine whether treadmill
      intervention improves gross motor function (two studies; effect estimate 0.88;
      95% CI: -4.54, 6.30). In the one study evaluating treadmill with and without
      orthotics, results suggested that adding orthotics might hinder gross motor
      progress (effect estimate -8.40; 95% CI: -14.55, -2.25).One study of children
      with Down syndrome measured the age of onset of assisted walking and reported
      those receiving the treadmill intervention were able to walk with assistance
      earlier than those who did not receive the intervention (effect estimate -74.00;
      95% CI: -135.40, -12.60). Another study comparing high and low intensity
      treadmill was unable to conclude whether one was more effective than the other in
      helping children achieve supported walking at an earlier age (effect estimate 
      1.86; 95% CI: -4.09, 0.37).One study of children at high risk of neuromotor
      disabilities evaluated step quality and found a statistically significant benefit
      from treadmill intervention compared to no treadmill intervention (effect
      estimate at 16 months of age: -15.61; 95% CI: -23.96, -7.27), but was not able to
      conclude whether there was a beneficial effect from treadmill training on step
      frequency at the same age (effect estimate at 16 months of age: 4.36; 95% CI: 
      2.63, 11.35). Step frequency was also evaluated in children with Down syndrome in
      another study and those who received high intensity rather than low intensity
      treadmill training showed an increased number of alternating steps (effect
      estimate 11.00; 95% CI: 6.03, 15.97).Our other primary outcome, falls and
      injuries due to falls, was not measured in any of the included studies. AUTHORS'
      CONCLUSIONS: The current review provided only limited evidence of the efficacy of
      treadmill intervention in children up to six years of age. Few studies have
      assessed treadmill interventions in young children using an appropriate control
      group (which would be usual treatment or no treatment). The available evidence
      indicates that treadmill intervention may accelerate the development of
      independent walking in children with Down syndrome. Further research is needed to
      confirm this and should also address whether intensive treadmill intervention can
      accelerate walking onset in young children with cerebral palsy and high risk
      infants, and whether treadmill intervention has a general effect on gross motor
      development in the various subgroups of young children at risk for developmental
      delay.

PMID- 22161450
TI  - Support surfaces for treating pressure ulcers.
AB  - BACKGROUND: Pressure ulcers are treated by reducing pressure on the areas of
      damaged skin. Special support surfaces (including beds, mattresses and cushions)
      designed to redistribute pressure, are widely used as treatments. The relative
      effects of different support surfaces are unclear. OBJECTIVES: To assess the
      effects of pressure-relieving support surfaces in the treatment of pressure
      ulcers. SEARCH METHODS: We searched: The Cochrane Wounds Group Specialised
      Register (searched 15 July 2011); The Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2011, Issue 3); Ovid MEDLINE (2007 to July
      Week 1 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, July 14,
      2011); Ovid EMBASE (2007 to 2011 Week 27); EBSCO CINAHL (2007 to 14 July 2011).
      The reference sections of included studies were also searched. SELECTION
      CRITERIA: We included published or unpublished randomised controlled trials
      (RCTs), that assessed the effects of support surfaces for treating pressure
      ulcers, in any patient group or setting, that reported an objective measure of
      wound healing. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of
      risk of bias were performed independently by two review authors. Trials with
      similar patients, comparisons and outcomes were considered for pooled analysis.
      Where pooling was inappropriate the results of the trials were reported
      narratively. Where possible, the risk ratio or mean difference was calculated for
      the results of individual studies. MAIN RESULTS: We identified 18 trials of
      support surfaces for pressure ulcer treatment, involving 1309 participants with
      samples sizes that ranged from 14 to 160. Of three trials comparing air-fluidized
      devices with conventional therapy, two reported significant reductions in
      pressure ulcer size associated with air-fluidized devices. Due to lack of
      reported variance data we could not replicate the analyses. In relation to three
      of the trials that reported significant reductions in pressure ulcer size
      favouring low air loss devices compared with foam alternatives, we found no
      significant differences. A small trial found that sheepskin placed under the legs
      significantly reduced redness and similarly a small subgroup analysis favoured a
      profiling bed compared with a standard bed in terms of the healing of existing
      grade 1 pressure ulcers. Poor reporting, clinical heterogeneity, lack of variance
      data and methodological limitations in the eligible trials meant that no pooled
      comparisons were undertaken. AUTHORS' CONCLUSIONS: There is no conclusive
      evidence about the superiority of any support surface for the treatment of
      existing pressure ulcers. Methodological issues included variations in outcomes
      measured, sample sizes and comparison groups. Many studies had small sample sizes
      and often there was inadequate description of the intervention, standard care and
      co-interventions. Individual study results were often inadequately reported, with
      failure to report variance data common, thus hindering the calculation of mean
      differences. Some studies did not report P values when reporting on differences
      in outcomes. In addition, the age of some trials (some being 20 years old), means
      that other technologies may have superseded those investigated.Further and
      rigorous studies are required to address these concerns and to improve the
      evidence base before firm conclusions can be drawn about the most effective
      support surfaces to treat pressure ulcers.

PMID- 22161451
TI  - Comparisons of approaches to pelvic floor muscle training for urinary
      incontinence in women.
AB  - BACKGROUND: Pelvic floor muscle training is the most commonly recommended
      physical therapy treatment for women with stress urinary incontinence. It is also
      sometimes recommended for mixed and, less commonly, urge urinary incontinence.
      The supervision and content of pelvic floor muscle training programmes are highly
      variable, and some programmes use additional strategies in an effort to increase
      adherence or training effects. OBJECTIVES: To compare the effects of different
      approaches to pelvic floor muscle training for women with urinary incontinence.
      SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials
      Register, which contains trials identified from the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE and CINAHL, and handsearching of journals
      and conference proceedings (searched 17 May 2011), and the reference lists of
      relevant articles. SELECTION CRITERIA: Randomised trials or quasi-randomised
      trials in women with stress, urge or mixed urinary incontinence (based on
      symptoms, signs or urodynamics). One arm of the study included pelvic floor
      muscle training. Another arm was an alternative approach to pelvic floor muscle
      training, such as a different way of teaching, supervising or performing pelvic
      floor muscle training. DATA COLLECTION AND ANALYSIS: We independently assessed
      trials for eligibility and methodological quality. We extracted then cross
      checked data. We resolved disagreements by discussion. We processed data as
      described in the Cochrane Handbook for Systematic Reviews of Interventions
      (version 5.2.2). We subgrouped trials by intervention. MAIN RESULTS: We screened
      574 records for eligibility and included 21 trials in the review. The 21 trials
      randomised 1490 women and addressed 11 comparisons. These were: differences in
      training supervision (amount, individual versus group), in approach (one versus
      another, the effect of an additional component) and the exercise training (type
      of contraction, frequency of training). In women with stress urinary
      incontinence, 10% of those who received weekly or twice-weekly group supervision
      in addition to individual appointments with the therapist did not report
      improvement post-treatment compared to 43% of the group who had individual
      appointments only (risk ratio (RR) for no improvement 0.29, 95% confidence
      interval (CI) 0.15 to 0.55, four trials). Looking at this another way, 90% of
      those who had combined group and individual supervision reported improvement
      versus 57% of women receiving individual supervision only. While women receiving
      the combination of frequent group supervision and individual supervision of
      pelvic floor muscle training were more likely to report improvement, the
      confidence interval was wide, and more than half of the 'control' group (the
      women who did not get the additional weekly or twice-weekly group supervision)
      reported improvement. This finding, of subjective improvement in both active
      treatment groups, with more improvement reported by those receiving more health
      professional contact, was consistent throughout the review.We feel there are
      several reasons why caution is needed when interpreting the results of the
      review: there were few data in any comparison; a number of trials were confounded
      by comparing two arms with multiple differences in the approaches to pelvic floor
      muscle training; there was a likelihood of a relationship between attention and
      reporting of more improvement in women who were not blind to treatment
      allocation; some trials chose interventions that were unlikely to have a muscle
      training effect; and some trials did not adequately describe their intervention.
      AUTHORS' CONCLUSIONS: This review found that the existing evidence was
      insufficient to make any strong recommendations about the best approach to pelvic
      floor muscle training. We suggest that women are offered reasonably frequent
      appointments during the training period, because the few data consistently showed
      that women receiving regular (e.g. weekly) supervision were more likely to report
      improvement than women doing pelvic floor muscle training with little or no
      supervision.

PMID- 22161452
TI  - Interventions to improve adherence to antiretroviral therapy in children with HIV
      infection.
AB  - BACKGROUND: Achieving and maintaining high levels of medication adherence are
      required to achieve the full benefits of antiretroviral therapy (ART), yet
      suboptimal adherence among children is common in both developed and developing
      countries. OBJECTIVES: To conduct a systematic review of the literature of
      evaluations of interventions for improving paediatric ART adherence. SEARCH
      METHODS: We created a comprehensive search strategy in order to identify all
      studies relevant to this topic. In July 2010, we searched the following
      electronic databases: EMBASE, MEDLINE, PsycINFO, Cochrane Central Register of
      Controlled Trials (CENTRAL), CINAHL, LILACS, Web of Science, Web of Social
      Science, NLM Gateway (supplemented by a manual search of the most recent
      abstracts not included in the Gateway database). We searched abstracts from the
      International AIDS Conference from 2002 to 2010, the International AIDS Society
      Conference on Pathogenesis, Treatment and Prevention from 2003 to 2009, and from
      the Conference on Retroviruses and Opportunistic Infections from 1997 to 2010. We
      used search strategies determined by the Cochrane Review Group on HIV/AIDS. We
      also contacted researchers who work in this field and checked reference lists of
      related systematic reviews and of all included studies. SELECTION CRITERIA:
      Randomised and non-randomised controlled trials of interventions to improve
      adherence to ART among children and adolescents (age <=18 years) were included.
      Studies had to report adherence to ART as an outcome. DATA COLLECTION AND
      ANALYSIS: After one author performed an initial screening to exclude citations
      that did not meet the inclusion criteria, two authors did a second screening of
      those citations that likely met the criteria. For all articles that passed the
      second screening, full articles were pulled in order to make a final
      determination. Two authors then extracted data and graded methodological quality
      independently. Differences were resolved through discussion. MAIN RESULTS: Four
      studies met the inclusion criteria. No single intervention was evaluated by more
      than one trial. Two studies were conducted in low-income countries. Two studies
      were randomised controlled trials (RCT), and two were non-randomised trials. An
      RCT of a home-based nursing programme showed a positive effect of the
      intervention on knowledge and medication refills (p=.002), but no effect on CD4
      count and viral load. A second RCT of caregiver medication diaries showed that
      the intervention group had fewer participants reporting no missed doses compared
      to the control group (85% vs. 92%, respectively), although this difference was
      not statistically significant (p=.08). The intervention had no effect on CD4
      percentage or viral load. A non-randomised trial of peer support group therapy
      for adolescents demonstrated no change in self-reported adherence, yet the
      percentage of participants with suppressed viral load increased from 30% to 80%
      (p=.06). The second non-randomised trial found that the percentage of children
      achieving >80% adherence was no different between children on a lopinavir
      ritonavir (LPV/r) regimen compared to children on a non-nucleoside reverse
      transcriptase regimen (p=.781). However, the proportion of children achieving
      virological suppression was significantly greater for children on the LPV/r
      regimen than for children on the NNRTI-containing regimen (p=.002). AUTHORS'
      CONCLUSIONS: A home-based nursing intervention has the potential to improve ART
      adherence, but more evidence is needed. Medication diaries do not appear to have
      an effect on adherence or disease outcomes. Two interventions, an LPV/r
      containing regimen and peer support therapy for adolescents, did not demonstrate
      improvements in adherence, yet demonstrated greater viral load suppression
      compared to control groups, suggesting a different mechanism for improved health
      outcomes. Well-designed evaluations of interventions to improve paediatric
      adherence to ART are needed.

PMID- 22161453
TI  - Relaxation techniques for pain management in labour.
AB  - BACKGROUND: Many women would like to avoid pharmacological or invasive methods of
      pain management in labour and this may contribute towards the popularity of
      complementary methods of pain management. This review examined currently
      available evidence supporting the use of relaxation therapies for pain management
      in labour. OBJECTIVES: To examine the effects of relaxation methods for pain
      management in labour on maternal and perinatal morbidity. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30
      November 2010), The Cochrane Complementary Medicine Field's Trials Register
      (November 2011), the Cochrane Central Register of Controlled Trials (The Cochrane
      Library 2010, Issue 4), MEDLINE (1966 to 30 November 2010), CINAHL (1980 to 30
      November 2010), the Australian and New Zealand Clinical Trial Registry (30
      November 2010), Chinese Clinical Trial Register (30 November 2010), Current
      Controlled Trials (30 November 2010), ClinicalTrials.gov, (30 November 2010)
      ISRCTN Register (30 November 2010), National Centre for Complementary and
      Alternative Medicine (NCCAM) (30 November 2010) and the WHO International
      Clinical Trials Registry Platform (30 November 2010). SELECTION CRITERIA:
      Randomised controlled trials comparing relaxation methods with standard care, no
      treatment, other non-pharmacological forms of pain management in labour or
      placebo. DATA COLLECTION AND ANALYSIS: Three review authors independently
      assessed trials for inclusion and extracted data. Data were checked for accuracy.
      Two review authors independently assessed trial quality. We attempted to contact
      study authors for additional information. MAIN RESULTS: We included 11 studies
      (1374 women) in the review. Relaxation was associated with a reduction in pain
      intensity during the latent phase (mean difference (MD) -1.25, 95% confidence
      interval (CI) -1.97 to -0.53, one trial, 40 women) and active phase of labour (MD
      -2.48, 95% CI -3.13 to 0.83, two trials, 74 women). There was evidence of
      improved outcomes from relaxation instruction with increased satisfaction with
      pain relief (risk ratio (RR) 8.00, 95% CI 1.10 to 58.19, one trial, 40 women) and
      lower assisted vaginal delivery (RR 0.07, 95% CI 0.01 to 0.50, two trials, 86
      women). Yoga was associated with reduced pain (mean difference (MD) -6.12, 95% CI
      -11.77 to -0.47), one trial, 66 women), increased satisfaction with pain relief
      (MD 7.88, 95% CI 1.51 to 14.25, one trial, 66 women), satisfaction with the
      childbirth experience (MD) 6.34, 95% CI 0.26 to 12.42, one trial, 66 women), and
      reduced length of labour when compared to usual care (MD -139.91, 95% CI -252.50
      to -27.32, one trial, 66 women) and when compared with supine position (MD 
      191.34, 95% CI -243.72 to -138.96, one trial, 83 women). Trials evaluating music
      and audio analgesia found no difference between groups in the primary outcomes
      pain intensity, satisfaction with pain relief, and caesarean delivery. The risk
      of bias was unclear for the majority of trials. AUTHORS' CONCLUSIONS: Relaxation
      and yoga may have a role with reducing pain, increasing satisfaction with pain
      relief and reducing the rate of assisted vaginal delivery. There was insufficient
      evidence for the role of music and audio-analgesia. However, there is a need for
      further research.

PMID- 22161454
TI  - The use of Cochrane Reviews in NICE clinical guidelines.

PMID- 22161455
TI  - We need access to all data from all clinical trials.

PMID- 22161456
TI  - Helping people make well-informed decisions before, during and after disasters:
      The Evidence Aid initiative.

PMID- 22161458
TI  - Recurrent early pregnancy loss.

PMID- 22161459
TI  - First trimester miscarriage evaluation.
AB  - Miscarriage is a relatively common occurrence for otherwise healthy women.
      Despite its frequency, evaluation for cause is rare. The most common cause of
      miscarriage is sporadic chromosome errors. Chromosomal analysis of the
      miscarriage offers an explanation in at least 50% of cases. Conventional
      cytogenetic evaluation can only be done on fresh tissue, so it is critical that
      the treating physician consider genetic testing at the time of the miscarriage.
      Ultrasound can estimate the gestational age at the time of miscarriage and
      identify major abnormalities in some embryos. A careful pathological examination
      can add to the evaluation by ruling out rare disorders with the highest
      recurrence risk. A multidisciplinary approach to miscarriage evaluation is
      essential to understanding the cause and risk of recurrence. A thorough
      evaluation of a miscarriage, in combination with emotional support, can often
      provide the necessary reassurance and confidence as the patient prepares for her
      next pregnancy.

PMID- 22161460
TI  - Management of recurrent pregnancy loss associated with a parental carrier of a
      reciprocal translocation: a systematic review.
AB  - This study reviews systematically the effectiveness of management strategies for
      carriers of a reciprocal translocation involving two chromosomes, ascertained on
      the basis of recurrent pregnancy loss. Subsequent pregnancy outcomes were
      tabulated based on whether management was medical or involved in vitro
      fertilization/preimplantation genetic diagnosis (IVF/PGD). A total of 129 cases
      from 13 articles met the criteria, of which 89% were managed medically. Before
      management, the overall live birthrate was 4% (19 of 484 pregnancies). Management
      was medical in 109 cases and IVF/PGD in 20 cases. Cumulative live birthrate was
      74% (81 of 109 cases) in the medical management group and 35% (7 of 20) in the
      IVF/PGD group. Based on this systematic review, successful pregnancy outcomes are
      high following either medical management or IVF/PGD for carriers of a reciprocal
      translocation, ascertained on the basis of recurrent pregnancy loss. But it is
      difficult to compare outcomes directly for these two strategies because of the
      different end points reported. Understanding the differences is essential for
      effective counseling. Until a well-designed study comparing the two strategies is
      performed, or at least prospective cohort studies with strict entry criteria and
      definitions, the cumulative experience and success of both medical management and
      IVF/PGD must be used to counsel patients who are carriers of a reciprocal
      translocation, ascertained on the basis of recurrent pregnancy loss.

PMID- 22161461
TI  - Endocrinology and recurrent early pregnancy loss.
AB  - Endocrine disorders have been frequently linked to recurrent pregnancy loss
      (RPL). Because embryo attachment and early implantation are exquisitely
      controlled by the local hormonal milieu, endocrine-related pregnancy failures are
      likely to occur early in gestation. Thyroid disorders, luteal phase defects, and
      polycystic ovary syndrome are the endocrine abnormalities most commonly
      associated with RPL. In this review we discuss new concepts in the
      pathophysiology and treatment of these diseases with the ultimate goal of
      improving pregnancy maintenance. We have also included our recommendations on
      testing and treatment of women with isolated and repeated pregnancy failure that
      is believed to be at least partially mediated by newly defined hypothyroidism,
      thyroid autoimmunity, luteal phase defects, obesity, and polycystic ovary
      syndrome.

PMID- 22161462
TI  - Clinical assessment and management of the endometrium in recurrent early
      pregnancy loss.
AB  - Unexplained and recurrent loss of pregnancies is a heartbreaking and frustrating
      condition. The routine diagnostic workup for pregnancy loss includes hormonal
      evaluation, screening for genetic or chromosomal defects, immunologic and
      thrombophilic testing, and evaluation of congenital or acquired Mullerian
      defects. In cases of idiopathic pregnancy loss, defects in endometrial
      receptivity are increasingly being investigated. The role of the endometrium in
      pregnancy loss has historical roots but remains controversial. Exciting new
      directions based on microRNAs, proteomics, and epigenetics promises to keep this
      area of investigation both interesting and complex. With each new diagnostic and
      therapeutic biomarker identified comes a greater potential for diagnosis and
      treatment of women. The clinical assessment of the endometrium remains an
      important part of the investigation of couples with unexplained pregnancy loss.

PMID- 22161463
TI  - Does obesity increase the risk of miscarriage in spontaneous conception: a
      systematic review.
AB  - Obesity has become an epidemic in developed societies. Retrospective studies
      suggest that obesity is associated with miscarriage in assisted reproduction. The
      objective of this study was to evaluate whether obesity is associated with
      miscarriage in spontaneous conception. We conducted a systematic review of
      published studies with pooled analysis. A literature review was performed.
      Studies in which fertility drugs or in vitro fertilization were used were
      excluded, unless data could be extracted for spontaneous conception. Data were
      compared for obese (body mass index [BMI]: >=28 or 30 kg/m (2)), overweight (BMI:
      25 to 29 kg/m (2)), and normal-weight (BMI: <25 kg/m (2)) women, with pooled odds
      ratios (ORs). Recurrent miscarriage data were analyzed separately. Six studies
      met the criteria for a cohort of 28,538 women. Pooled analysis revealed a higher
      miscarriage rate of 13.6% in 3800 obese versus 10.7% in 17,146 normal-BMI women
      (OR: 1.31; 95% confidence interval [CI], 1.18 to 1.46). Although the cohort was
      small, there was a higher prevalence of recurrent early miscarriage in obese
      versus normal-BMI women (0.4% versus 0.1%; OR: 3.51; 95% CI, 1.03 to 12.01). In
      women with recurrent miscarriage, there was a higher miscarriage rate in the
      obese versus nonobese women (46% versus 43%; OR: 1.71; 95% CI, 1.05). Based on
      retrospective studies, we concluded that obesity is associated with a higher
      miscarriage rate in women who conceive spontaneously. Larger prospective studies
      are urgently needed to verify these preliminary results.

PMID- 22161464
TI  - Uterine anomaly and recurrent pregnancy loss.
AB  - Women with recurrent pregnancy loss have a 3.2 to 6.9% likelihood of having a
      major uterine anomaly and a 1.0 to 16.9% chance of having an arcuate uterus.
      Bicornuate and septate uterine have a negative impact on reproductive outcomes
      and are associated with subsequent euploid miscarriage. The impact of an arcuate
      uterus on pregnancy outcome remains unclear. There are no definitive criteria to
      distinguish among the arcuate, septate, and bicornuate uteri. The American
      Fertility Society classification of Mullerian anomalies is the most common
      standardized classification of uterine anomalies. According to estimates, 65 to
      85% of patients with bicornuate or septate uteri have a successful pregnancy
      outcome after metroplasty. However, 59.5% of the patients with such anomalies
      have a successful subsequent pregnancy without surgery, with a cumulative live
      birthrate of 78.0%. There is no case-control study to compare live birthrates in
      women who had surgery compared with those who did not. Strict criteria to
      distinguish between the bicornuate and septate uterus should be established.
      Further study is needed to confirm the benefits of metroplasty.

PMID- 22161465
TI  - Obstetric antiphospholipid syndrome: an update on pathophysiology and management.
AB  - Antiphospholipid antibodies (aPLs) are acquired antibodies directed against
      negatively charged phospholipids, a group of inner and outer cell membrane
      antigens found in mammals. Obstetric antiphospholipid antibody syndrome (APS) is
      diagnosed in the presence of certain clinical features in conjunction with
      positive laboratory findings. Although obstetric APS was originally reported in
      association with slow progressive thrombosis and infarction in the placenta, it
      is most often associated with a poor obstetric outcome. In fact, obstetric APS is
      one of the most commonly identified causes of recurrent pregnancy loss (RPL).
      Thus obstetric APS is distinguished from APS in other organ systems where the
      most common manifestation is thrombosis. Several pathophysiological mechanisms of
      action of aPLs have been described. The most common histopathological finding in
      early pregnancy loss has been defective endovascular decidual trophoblastic
      invasion. Treatment with heparin and aspirin is emerging as the therapy of
      choice, with ~75% of treated women with RPL and aPLs having a successful delivery
      compared with <50% without treatment. This review highlights the diagnostic
      challenges of obstetric APS, the obstetric complications associated with APS,
      proposed pathophysiological mechanisms of APS during pregnancy, and the
      management of women during and after pregnancy.

PMID- 22161466
TI  - Testing for inherited thrombophilia in recurrent miscarriage.
AB  - Approximately 1-5% of women trying to conceive experience recurrent miscarriage,
      and in 50% of these women, the cause of the preceding miscarriages is unknown.
      Inherited thrombophilias such as factor V Leiden mutation, prothrombin gene
      mutation (PT 20210A), and deficiencies of natural anticoagulants protein C,
      protein S, and antithrombin are associated with recurrent miscarriage. Knowledge
      of the association between inherited thrombophilia and recurrent miscarriage and
      of potential treatment options for improving chances of a live birth could tempt
      physicians to test for inherited thrombophilia in women with recurrent
      miscarriage. However, the strength of the association between inherited
      thrombophilia and recurrent miscarriage is not very strong, and more importantly,
      no evidence indicates that the use of anticoagulants improves the chance of live
      birth in these women. With the current state of evidence, testing for inherited
      thrombophilia should not lead to altered clinical management and therefore,
      should not be performed routinely in women with recurrent miscarriage but only in
      the context of scientific studies.

PMID- 22161467
TI  - Is there a role for assisted reproductive technology in recurrent miscarriage?
AB  - Unexplained recurrent miscarriage (RM) is a significant health problem for which
      no effective treatment is available yet. In only 50% of couples with RM a cause
      can be found. In clinical practice, a frequently asked question is whether
      assisted reproductive technology (ART) is a treatment option. The scientific
      rationale and the chances of success for ART in couples with unexplained RM are
      still controversial. Presently, there is not enough evidence to justify IVF or
      intrauterine insemination (IUI) as a treatment option. Research on oocyte
      donation has been reported in one article. It is questionable whether couples
      with unexplained RM would undergo the potential risks and emotional aspects of
      ART. There is insufficient data on whether preimplantation genetic diagnosis
      improves the live birthrate in carriers of a structural chromosome rearrangement
      with a history of RM. No randomized controlled trials are available for
      preimplantation genetic screening (PGS) for unexplained RM. A recently published
      review concluded that the live birthrate for IVF/PGS and natural conception
      groups appears to be quite similar. Because evidence is lacking, we recommend
      refraining from ART in couples with recurrent miscarriage.

PMID- 22161468
TI  - The importance of preconception counseling and early pregnancy monitoring.
AB  - Preconception counseling plays a key role in preparing for a pregnancy. In
      couples with a history of recurrent early pregnancy loss, counseling is of
      particular importance because women are invariably more distressed and require
      reassurance that everything possible is being done to avoid future pregnancy
      losses. Because their subsequent pregnancies are more likely to be planned and
      these patients may be more willing to adopt recommendations that have been
      offered to them, it becomes more important to identify which investigations and
      interventions are the most beneficial. Several interventions ranging from genetic
      testing to lifestyle changes and medications may have a positive effect on the
      chances of a successful pregnancy. Early pregnancy monitoring and support
      increases the chance of a live birth and helps to predict potential future
      pregnancy complications. Recent research suggests that events that occur in the
      uterine decidua, even before a woman knows she is pregnant, may have a
      significant impact on fetal growth and the outcome of pregnancy. With this in
      mind, shifting future research and clinical practice to focus on the
      periconceptual period and the very early stages of pregnancy should offer
      significant benefits to the health of both the mother and her infant. The overall
      aim should be to effectively use every pregnancy as the health-care opportunity
      of two lifetimes.

PMID- 22161470
TI  - Myeloperoxidase inhibition ameliorates multiple system atrophy-like degeneration
      in a transgenic mouse model.
AB  - Multiple system atrophy (MSA) is a rare and fatal alpha-synucleinopathy
      characterized by a distinctive oligodendrogliopathy with glial cytoplasmic
      inclusions and associated neuronal multisystem degeneration. The majority of
      patients presents with a rapidly progressive parkinsonian disorder and atypical
      features such as early autonomic failure and cerebellar ataxia. We have
      previously reported that complete MSA pathology can be modeled in transgenic mice
      overexpressing oligodendroglial alpha-synuclein under conditions of oxidative
      stress induced by 3-nitropropionic acid (3-NP) including striatonigral
      degeneration, olivopontocerebellar atrophy, astrogliosis, and microglial
      activation. Here, we show that myeloperoxidase (MPO), a key enzyme involved in
      the production of reactive oxygen species by phagocytic cells, is expressed in
      both human and mouse MSA brains. We also demonstrate that in the MSA mouse model,
      MPO inhibition reduces motor impairment and rescues vulnerable neurons in
      striatum, substantia nigra pars compacta, cerebellar cortex, pontine nuclei, and
      inferior olives. MPO inhibition is associated with suppression of microglial
      activation but does not affect 3-NP induced astrogliosis in the same regions.
      Finally, MPO inhibition results in reduced intracellular aggregates of alpha
      synuclein. This study suggests that MPO inhibition may represent a novel
      candidate treatment strategy against MSA-like neurodegeneration acting through
      its anti-inflammatory and anti-oxidative properties.

PMID- 22161471
TI  - Social integration of people with severe mental illness: relationships between
      symptom severity, professional assistance, and natural support.
AB  - Reducing dependency on professionals and social integration has been a major goal
      of recovery-oriented mental health services. This cross-sectional study examined
      531 male outpatients at three public mental health centers in Southern
      Connecticut. Hierarchical multiple regression analyses were conducted to answer:
      (1) Do clients who have more severe clinical problems rely more on professional
      support and mental health services, and rely less on natural supports? (2) Do
      clients who have greater natural supports rely less on professional support and
      mental health services? Results found clients with more severe clinical problems
      do not rely more on professional support and report less natural social support.
      Natural support was also found to be a complement, rather than a substitute for
      professional support. These findings suggest the social integration of male
      clients with severe mental illness may include being more connected to mental
      health providers even as they develop increasing natural supports.

PMID- 22161472
TI  - Surface plasmon resonance and NMR analyses of anti Tn-antigen MLS128 monoclonal
      antibody binding to two or three consecutive Tn-antigen clusters.
AB  - Tn-antigens are tumour-associated carbohydrate antigens that are involved in
      metastatic processes and are associated with a poor prognosis. MLS128 monoclonal
      antibody recognizes the structures of two or three consecutive Tn-antigens (Tn2
      or Tn3). Since MLS128 treatment inhibits colon and breast cancer cell growth
      [Morita, N., Yajima, Y., Asanuma, H., Nakada, H., and Fujita-Yamaguchi, Y. (2009)
      Inhibition of cancer cell growth by anti-Tn monoclonal antibody MLS128. Biosci.
      Trends 3, 32-37.], understanding the interaction between MLS128 and Tn-clusters
      may allow us to the development of novel cancer therapeutics. Although MLS128 was
      previously reported to have specificity for Tn3 rather than Tn2, similar levels
      of Tn2/Tn3 binding were unexpectedly observed at 37 degrees C. Thus,
      thermodynamic analyses were performed via surface plasmon resonance (SPR) using
      synthetic Tn2- and Tn3-peptides at 10, 15, 20, 25 and 30 degrees C. SPR results
      revealed that MLS128's association constants for both antigens were highly
      temperature dependent. Below 25 degrees C MLS128's association constant for Tn3
      peptide was clearly higher than that for Tn2-peptide. At 30 degrees C, however,
      the association constant for Tn2-peptide was higher than that for Tn3-peptide.
      This reversal of affinity is due to the sharp increase in K(d) for Tn3. These
      results were confirmed by NMR, which directly measured MLS128-Tn binding in
      solution. This study suggested that thermodynamic control plays a critical role
      in the interaction between MLS128/Tn2 and MLS128/Tn3.

PMID- 22161473
TI  - [Effect of brimonidine on central corneal thickness].
AB  - BACKGROUND: Brimonidine, an alpha-2 adrenoceptor agonist, is widely used in
      glaucoma treatment. Although it is known that it is quickly taken up by the
      cornea following topical administration and although it is well established that
      the cornea expresses alpha-2 adrenoceptors there are only few studies available
      on the impact brimonidine has on the cornea. The aim of the present study was to
      show if topical application of brimonidine leads to an interaction with corneal
      alpha-2 adrenoceptors in terms of an increase in central corneal thickness.
      MATERIALS AND METHODS: Ten healthy test persons (five female and five male
      subjects) - mean age 30 +/- 7years - were tested in a pilot study. Measured were
      intraocular pressure, epithelial, stromal and endothelial thickness before as
      well as ten minutes, 24, 48, 72 and 96 hours after administration of brimonidine
      0.1 % eye drops twice daily. To check the impact of this medication, sodium
      hyaluronate eye drops were administered to the other eye twice daily. RESULTS:
      Administration of brimonidine 0.1 % resulted in a reduction of intraocular
      pressure from an initial value of 17 +/- 2 mmHg to 13 +/- 4 mmHg after four days
      (p = 0.001) as well as an increase in total corneal thickness from 559 +/- 8 MUm
      from the time of the baseline examination to 581 +/- 11 MUm (p < 0.001), an
      increase of epithelial thickness from 61 +/- 1 MUm to 68 +/- 7 MUm (p = 0.008)
      and stromal thickness from 488 +/- 8 MUm to 503 +/- 8 MUm (p < 0.001) after two
      days each. Another two days later total corneal thickness was 566 +/- 10 MUm (p =
      0.032), epithelial thickness 64 +/- 3 MUm (p = 0.104) and stromal thickness 492
      +/- 8 MUm (p = 0.139), which means that the values had returned more or less to
      the initial values measured. In contrast, endothelial thickness did not vary
      following administration of brimonidine 0.1 % (p = 0.109). CONCLUSION: Topical
      administration of brimonidine 0.1 % results in a reversible increase in corneal
      thickness. The question as to whether this increase is of clinical significance
      has to be answered by larger studies.

PMID- 22161474
TI  - Finite mixture varying coefficient models for analyzing longitudinal heterogenous
      data.
AB  - This paper aims to develop a mixture model to study heterogeneous longitudinal
      data on the treatment effect of heroin use from a California Civil Addict
      Program. Each component of the mixture is characterized by a varying coefficient
      mixed effect model. We use the Bayesian P-splines approach to approximate the
      varying coefficient functions. We develop Markov chain Monte Carlo algorithms to
      estimate the smooth functions, unknown parameters, and latent variables in the
      model. We use modified deviance information criterion to determine the number of
      components in the mixture. A simulation study demonstrates that the modified
      deviance information criterion selects the correct number of components and the
      estimation of unknown quantities is accurate. We apply the proposed model to the
      heroin treatment study. Furthermore, we identify heterogeneous longitudinal
      patterns.

PMID- 22161475
TI  - Two-year drinking water carcinogenicity study of methyl tertiary-butyl ether
      (MTBE) in Wistar rats.
AB  - Methyl tertiary-butyl ether (MTBE) has been used as a gasoline additive to reduce
      tailpipe emissions and its use has been discontinued. There remains a concern
      that drinking water sources have been contaminated with MTBE. A two-year drinking
      water carcinogenicity study of MTBE was conducted in Wistar rats (males, 0, 0.5,
      3, 7.5 mg ml(-1); and females, 0, 0.5, 3, and 15 mg ml(-1)). Body weights were
      unaffected and water consumption was reduced in MTBE-exposed males and females.
      Wet weights of male kidneys were increased at the end of two years of exposure to
      7.5 mg ml(-1) MTBE. Chronic progressive nephropathy was observed in males and
      females, was more severe in males, and was exacerbated in the high MTBE exposure
      groups. Brain was the only tissue with a statistically significant finding of
      neoplasms. One astrocytoma (1/50) was found in a female rat (15 mg ml(-1)). The
      incidence of brain astrocytomas in male rats was 1/50, 1/50, 1/50 and 4/50 for
      the 0, 0.5, 3 and 7.5 mg ml(-1) exposure groups, respectively. This was a
      marginally significant statistical trend, but not statistically significant when
      pairwise comparisons were made or when multiple comparisons were taken into
      account. The incidence of astrocytoma fell within historical control ranges for
      Wistar rats, and the brain has not been identified as a target organ following
      chronic administration of MTBE, ethyl tert-butyl ether, or tertiary butyl alcohol
      (in drinking water) to mice and rats. We conclude that the astrocytomas observed
      in this study are not associated with exposure to MTBE.

PMID- 22161476
TI  - Different effects of dihydropyridine calcium channel antagonists on CYP3A4 enzyme
      of human liver microsomes.
AB  - The present study investigated inhibitory effects of 1,4-dihydropyridines (1,4
      DHPs) calcium channel antagonists (1,4-DHP-CCAs) on cytochromeP450 3A4 (CYP3A4)
      of human liver microsomes and further explored importance of 1,4-DHPs molecular
      structural descriptors. Partial Least Squares method was applied to probe the
      quantitative relationships between the 1,4-DHPs molecular structural descriptors
      and its inhibitory actions, which demonstrated that different 1,4-DHP-CCAs could
      inhibit CYP3A4 enzyme's activity differently. The K (i) values of nicardipine,
      lercandipine, cilnidipine, nitrendipine, lacidipine, nifedipine, felodipine were
      10.13, 10.17, 11.44, 23.90, 29.34, 29.06 and 32.64 MUmol L-1, respectively. It is
      suggested that the 1,4-DHPs molecular structural descriptors are the most
      important for its inhibitory effects based on the quantitative structure-activity
      relationship (QSAR) formula. The LogP was positively correlated to the K (i),
      whereas molecular weight and molecule volume were negatively correlated. It is
      concluded that analysis of K (i) of 1,4-DHPs derivatives on the CYP3A4 activity
      may apply for the QSAR formula at the initial stage of clinical application of
      new drugs.

PMID- 22161495
TI  - Vancomycin-induced red man syndrome in pediatric oncology: still an issue?
AB  - Red man syndrome is a rare but possibly serious adverse reaction during treatment
      with intravenous vancomycin. It is extremely important that pediatricians,
      especially in oncology, recognize this reaction and treat it appropriately.
      Following two case-reports from a pediatric oncology setting, a series of
      practical recommendations to prevent or handle red man syndrome are described.

PMID- 22161496
TI  - A simple isotropic phantom for diffusional kurtosis imaging.
AB  - Dairy cream is shown to be a simple, inexpensive, isotropic phantom useful for
      testing diffusional kurtosis imaging data acquisition and postprocessing. The MR
      visible protons of cream exhibit slow and fast diffusion components, attributed
      to the fat and water protons, respectively, which give rise to a diffusion
      coefficient of 1.1 MUm(2)/ms and a diffusional kurtosis of 1.2. These parameter
      values are similar to those observed in vivo for human brain. Heating the cream
      is found to increase the T(2)-relaxation time of the fat protons, which
      facilitates the evaluation of typical diffusional kurtosis imaging protocols used
      in clinical settings. The diffusion coefficient and diffusional kurtosis can both
      be measured directly and predicted based on the corresponding diffusion
      parameters of the individual water and fat components, which are independently
      measurable due to chemical shift misregistration, thus providing an important
      consistency check. This phantom is proposed as a convenient calibration standard
      for multicenter diffusional kurtosis imaging studies.

PMID- 22161497
TI  - Feasibility and performance of the FibroScan XL probe.

PMID- 22161498
TI  - Signaling of cytokines is important in regulation of GnRH neurons.
AB  - Cytokines encompass a broad class of peptides that mediate signals in a broad
      range of physiological situations including inflammation, infection, and obesity.
      The cytokine receptor-associated tyrosine kinase, Jak2, is one of the most
      important proteins mediating cytokine signaling pathway activation. Recently, our
      group has demonstrated that Jak2 signaling in the gonadotropin-releasing hormone
      (GnRH) neuron plays a critical role in fertility in males and females,
      implicating cytokine activation of the neuron in GnRH neuronal development and
      function. To date, the specific cytokine(s) essential for activating Jak2 during
      neuroendocrine development are not known. In this article, we review the evidence
      for the role of several class 1 cytokines in regulating GnRH neuronal
      development, GnRH secretion, and GnRH expression.

PMID- 22161501
TI  - Mercury concentration in the breast milk of Iranian women.
AB  - Human milk is usually the only source of food for infants during the first 4 to 5
      months of their life. In this research, 80 human milk samples were collected from
      mothers in Tehran, Noushahr and the countryside of Tabriz, Iran, who were not
      occupationally exposed to mercury. The mean concentration of mercury in breast
      milk obtained from mothers in the countryside of Tabriz, Noushahr and Tehran was
      0.86, 0.15 and 0.12 MUg/L, respectively. There was a significant difference in
      mercury concentration in human breast milk between that from the countryside of
      Tabriz with that from Tehran and Noushahr. Only 3.7% of infant samples (three
      infants) had mercury concentration higher than normal versus the WHO recommended
      limit (0.5 MUg g(-1)). The fish consumption of these mothers in Tehran and
      Noushahr was a factor that significantly affected the mercury concentration in
      their breast milk. Also, their age affected the mercury levels in breast milk (p
      = 0.04).

PMID- 22161500
TI  - Metabolic changes of cerebrum by repetitive transcranial magnetic stimulation
      over lateral cerebellum: a study with FDG PET.
AB  - To better understand the functional role of cerebellum within the large-scale
      cerebellocerebral neural network, we investigated the changes of neuronal
      activity elicited by cerebellar repetitive transcranial magnetic stimulation
      (rTMS) using (18)F-fluorodeoxyglucose (FDG) and positron emission tomography
      (PET). Twelve right-handed healthy volunteers were studied with brain FDG PET
      under two conditions: active rTMS of 1 Hz frequency over the left lateral
      cerebellum and sham stimulation. Compared to the sham condition, active rTMS
      induced decreased glucose metabolism in the stimulated left lateral cerebellum,
      the areas known to be involved in voluntary motor movement (supplementary motor
      area and posterior parietal cortex) in the right cerebral hemisphere, and the
      areas known to be involved in cognition and emotion (orbitofrontal, medial
      frontal, and anterior cingulate gyri) in the left cerebral hemisphere. Increased
      metabolism was found in cognition- and language-related brain regions such as the
      left inferior frontal gyrus including Broca's area, bilateral superior temporal
      gyri including Wernicke's area, and bilateral middle temporal gyri. Left
      cerebellar rTMS also led to increased metabolism in the left cerebellar dentate
      nucleus and pons. These results demonstrate that rTMS over the left lateral
      cerebellum modulates not only the target region excitability but also
      excitability of remote, but interconnected, motor-, language-, cognition-, and
      emotion-related cerebral regions. They provide further evidence that the
      cerebellum is involved not only in motor-related functions but also in higher
      cognitive abilities and emotion through the large-scale cerebellocereberal neural
      network.

PMID- 22161502
TI  - Relationship between serum lithium, salivary lithium, and urinary lithium in
      patients on lithium therapy.
AB  - Lithium carbonate is used in the treatment of both psychiatric and nonpsychiatric
      disorders. The aim of this study was to explore the relationship between serum
      lithium, salivary lithium, and urinary lithium. Blood, saliva, and urine samples
      were collected from 50 patients, and estimation of serum, salivary, and urine
      lithium was done using an atomic absorption spectrophotometer. Mean serum lithium
      was 0.75 +/- 0.25 mEq/L, mean salivary lithium was 1.91 +/- 0.80 mEq/L, and mean
      urine lithium was 7.16 +/- 4.84 mEq/L. A significant direct correlation was found
      between serum lithium and salivary lithium (r = 0.695, p < 0.001). This
      correlation was higher in females (r = 0.770, p < 0.001) when compared to males
      (r = 0.665, p < 0.001). Even though a significant correlation was found between
      serum and salivary lithium levels, more studies are needed in this domain to
      establish salivary therapeutic monitoring as a feasible option for patients on
      lithium carbonate therapy.

PMID- 22161503
TI  - Postmortem role of calpains in Pekin duck skeletal muscles.
AB  - BACKGROUND: It is generally agreed that calpains are involved in postmortem
      proteolysis of skeletal muscle and improve meat tenderness. However, little
      information regarding the postmortem role of calpains in duck skeletal muscle is
      known. Therefore, the purpose of this study was to examine the role of calpains
      in Pekin duck postmortem breast muscles (BM) and leg and thigh muscles (LM)
      muscles at 5  degrees C. RESULTS: The postmortem pH was lower (P < 0.05) in BM
      than in LM. Western blots indicated that postmortem desmin degradation and the
      30/32 kDa troponin-T degradation product accumulation were more rapid in BM than
      in LM. Casein zymograms showed that at-death u-calpain activity was higher in BM
      than in LM. As time post mortem increased, u-calpain was activated and autolyzed
      more rapidly and extensively in BM than in LM, but u/m-calpain was activated at a
      relative slower rate compared with u-calpain. Correlation results showed that u
      calpain activity, rather than u/m-calpain activity, in BM samples was highly
      correlated with the abundance of desmin and the 30/32 kDa troponin-T degradation
      components across the postmortem period. However, no such correlations were found
      with LM u- and u/m-calpains. CONCLUSION: Therefore, our results suggest that BM u
      calpain with a faster and more extensive activation and autolysis would play a
      relatively dominant role in dictating degradation of desmin and troponin-T in
      postmortem duck muscle.

PMID- 22161504
TI  - Ceramicines J-L, new limonoids from Chisocheton ceramicus.
AB  - Three new limonoids, ceramicines J (1), K (2), and L (3), were isolated from the
      hexane layer of Chisocheton ceramicus bark extract. Their structures were
      elucidated from 1D and 2D NMR data. Ceramicines J-L (1-3) exhibited dose
      dependent moderate cytotoxicity against the HL-60 cell line.

PMID- 22161499
TI  - Consensus paper: roles of the cerebellum in motor control--the diversity of ideas
      on cerebellar involvement in movement.
AB  - Considerable progress has been made in developing models of cerebellar function
      in sensorimotor control, as well as in identifying key problems that are the
      focus of current investigation. In this consensus paper, we discuss the
      literature on the role of the cerebellar circuitry in motor control, bringing
      together a range of different viewpoints. The following topics are covered:
      oculomotor control, classical conditioning (evidence in animals and in humans),
      cerebellar control of motor speech, control of grip forces, control of voluntary
      limb movements, timing, sensorimotor synchronization, control of corticomotor
      excitability, control of movement-related sensory data acquisition, cerebro
      cerebellar interaction in visuokinesthetic perception of hand movement,
      functional neuroimaging studies, and magnetoencephalographic mapping of cortico
      cerebellar dynamics. While the field has yet to reach a consensus on the precise
      role played by the cerebellum in movement control, the literature has witnessed
      the emergence of broad proposals that address cerebellar function at multiple
      levels of analysis. This paper highlights the diversity of current opinion,
      providing a framework for debate and discussion on the role of this
      quintessential vertebrate structure.

PMID- 22161505
TI  - A dynamic model for the risk of bladder cancer progression.
AB  - We propose a multistate modeling approach to describe the observed evolution of
      patients diagnosed with non-muscle-invasive bladder cancer. On the basis of data
      from the Spanish Bladder Cancer/EPICURO study, we adjust a multistate model
      taking into account the disease-related events of interest (recurrence,
      progression, and disease-related deaths) as well as competing deaths due to other
      causes. We then develop a dynamic predictive process for bladder cancer
      progression, which allows the risk of a patient to be updated whenever new
      information of his or her evolution is available. By using specific measures of
      prospective accuracy in the presence of competing risks, the proposed dynamic
      model has shown to improve prediction accuracy and provides a more personalized
      management of bladder patients.

PMID- 22161506
TI  - Low-dose probenecid selectively inhibits urinary excretion of
      phenolsulfonphthalein in rats without affecting biliary excretion.
AB  - Renal organic anion transport systems play an important role in the excretion of
      anionic drugs and toxic compounds. Probenecid has been used as a potent inhibitor
      of urinary and biliary excretion of anionic compounds mediated by transporters
      such as organic anion transporters and multidrug resistance-associated protein 2
      (Mrp2). The purpose of this study was to optimize the dose of probenecid required
      for selective inhibition of urinary excretion of anionic compounds in rats,
      without inhibition of biliary excretion. Phenolsulfonphthalein (PSP), a model
      anionic compound that is excreted in urine and bile, was intravenously
      administered to rats after intraperitoneal injection of different doses of
      probenecid (0, 0.2, 2, 10, 100, 200 and 400 mg kg(-1) ). Treatment with 100, 200
      or 400 mg kg(-1) probenecid decreased both renal clearance (CLr ) and biliary
      clearance (CLb ) of PSP, whereas 0.2 mg kg(-1) probenecid did not have any
      effect. Probenecid administered at doses of 2 and 10 mg kg(-1) decreased only CLr
      . The median effective doses of probenecid for inhibiting CLr and CLb were 0.925
      and 23.9 mg kg(-1) , respectively. These data suggest that a low dose of
      probenecid selectively inhibits urinary excretion of PSP that may be mediated by
      organic anion transporters, without affecting biliary excretion that may be
      mediated by Mrp2.

PMID- 22161507
TI  - [Sleep disturbances in childhood - the rank of polysomnography].

PMID- 22161508
TI  - Electron transfer dissociation (ETD) of peptides containing intrachain disulfide
      bonds.
AB  - The fragmentation chemistry of peptides containing intrachain disulfide bonds was
      investigated under electron transfer dissociation (ETD) conditions. Fragments
      within the cyclic region of the peptide backbone due to intrachain disulfide bond
      formation were observed, including: c (odd electron), z (even electron), c-33 Da,
      z+33 Da, c+32 Da, and z-32 Da types of ions. The presence of these ions indicated
      cleavages both at the disulfide bond and the N-Calpha backbone from a single
      electron transfer event. Mechanistic studies supported a mechanism whereby the N
      Calpha bond was cleaved first, and radical-driven reactions caused cleavage at
      either an S-S bond or an S-C bond within cysteinyl residues. Direct ETD at the
      disulfide linkage was also observed, correlating with signature loss of 33 Da
      (SH) from the charge-reduced peptide ions. Initial ETD cleavage at the disulfide
      bond was found to be promoted amongst peptides ions of lower charge states, while
      backbone fragmentation was more abundant for higher charge states. The capability
      of inducing both backbone and disulfide bond cleavages from ETD could be
      particularly useful for sequencing peptides containing intact intrachain
      disulfide bonds. ETD of the 13 peptides studied herein all showed substantial
      sequence coverage, accounting for 75%-100% of possible backbone fragmentation.

PMID- 22161509
TI  - Supercharging protein complexes from aqueous solution disrupts their native
      conformations.
AB  - The effects of aqueous solution supercharging on the solution- and gas-phase
      structures of two protein complexes were investigated using traveling-wave ion
      mobility-mass spectrometry (TWIMS-MS). Low initial concentrations of m
      nitrobenzyl alcohol (m-NBA) in the electrospray ionization (ESI) solution can
      effectively increase the charge of concanavalin A dimers and tetramers, but at
      higher m-NBA concentrations, the increases in charge are accompanied by solution
      phase dissociation of the dimers and up to a ~22% increase in the collision cross
      section (CCS) of the tetramers. With just 0.8% m-NBA added to the ESI solution of
      a ~630 kDa anthrax toxin octamer complex, the average charge is increased by only
      ~4% compared with the "native" complex, but it is sufficiently destabilized so
      that extensive gas-phase fragmentation occurs in the relatively high pressure
      regions of the TWIMS device. Anthrax toxin complexes exist in either a prechannel
      or a transmembrane channel state. With m-NBA, the prechannel state of the complex
      has the same CCS/charge ratio in the gas phase as the transmembrane channel state
      of the same complex formed without m-NBA, yet undergoes extensive dissociation,
      indicating that destabilization from supercharging occurs in the ESI droplet
      prior to ion formation and is not a result of Coulombic destabilization in the
      gas phase as a result of higher charging. These results demonstrate that the
      supercharging of large protein complexes is the result of conformational changes
      induced by the reagents in the ESI droplets, where enrichment of the
      supercharging reagent during droplet evaporation occurs.

PMID- 22161539
TI  - Environmental factors associated with Crohn's disease in India.
AB  - BACKGROUND: The frequency of diagnosis of Crohn's disease (CD) in India is
      increasing. This case-control study was designed to detect associations of
      environmental and dietary factors with the diagnosis of CD. METHODS: In 200
      consecutive patients with CD and 200 control subjects without gastrointestinal
      disease, environmental hygiene exposures in childhood and in the past one year,
      and dietary preferences were recorded using a questionnaire. Univariate and
      multivariate analyses were done. RESULTS: In univariate analysis, CD showed
      positive association with urban residence (at birth and current), availability of
      protected drinking water (childhood and current), availability of piped water in
      the house (childhood and current), and strict vegetarian dietary habit, and
      negative association with regular fish consumption and presence of cattle in the
      house compound. Multivariate analysis showed that regular fish consumption (OR
      0.52, 95% CI 0.33-0.80, p = 0.003), and presence of cattle in the house compound
      currently (OR 0.57, 95% CI 0.35-0.92, p = 0.023) were significant protective
      associations, whereas use of safe drinking water was positively associated (OR
      1.59, 95% CI 1.02-2.47, p = 0.042) with the disease. CONCLUSION: Occurrence of CD
      was associated with dietary and environmental exposures, which indicate that diet
      and hygiene may influence the development of this disease.

PMID- 22161540
TI  - Effect of bovine colostrum-based food supplement in the treatment of HIV
      associated diarrhea in Northern Uganda: a randomized controlled trial.
AB  - AIM: HIV-associated diarrhea is common in HIV/AIDS patients in developing
      countries. An earlier uncontrolled study showed that a nutritional product made
      from bovine colostrum (ColoPlus(r)) alleviates HIV-associated diarrhea. We
      performed a randomized single-blind controlled trial of addition of colostrum
      based supplement (ColoPlus(r)) to standard anti-diarrhea treatment in HIV/AIDS
      patients with diarrhea. METHODS: Eighty-seven adult patients with HIV-associated
      diarrhea were recruited at Gulu Hospital and four community clinics in Northern
      Uganda. Forty-five patients were randomized to receive 50 g of colostrum-based
      supplement twice a day for 4 weeks in addition to standard anti-diarrhea
      treatment, and 42 patients received standard anti-diarrhea treatment alone.
      Patients were followed up for 9 weeks. Daily stool frequency was recorded, and
      body weight and body mass index were evaluated at weeks 1, 4 and 9. Baseline CD4+
      count was measured at baseline and at week 9. RESULTS: Mean daily stool frequency
      decreased by 79% from 7.5 to 1.3 motions over the study period in patients on
      colostrum-based supplement, compared to a 58% reduction in controls (p < 0.001).
      Self-reported fatigue was reduced by 85% in patients on colostrum-based
      supplement by week 9 compared to 43% reduction amongst controls (p < 0.001).
      Patients on colostrum-based supplement had 11% increase (p < 0,001) in mean body
      weight and body mass index by week 9, but no changes were observed in control
      subjects. Mean CD4+ count increased by 14% for patients on colostrum-based
      supplement, in contrast to 12% decrease in controls (p < 0.001). CONCLUSIONS:
      This study shows that addition of colostrum-based supplement to standard therapy
      is effective in treatment of HIV-associated diarrhea.

PMID- 22161541
TI  - Cystic duct clip migration into the common bile duct.

PMID- 22161542
TI  - Safety of the hepatitis E vaccine for pregnant women: a preliminary analysis.

PMID- 22161543
TI  - Complications of endoscopic surgery of the pituitary adenomas: analysis of 570
      patients and review of the literature.
AB  - Endoscopic transsphenoidal surgery is emerging as a minimally invasive and
      maximally effective procedure for pituitary adenomas. In this report we analyzed
      the complications in 624 procedures of endonasal transsphenoidal endoscopic
      surgery in the treatment of 570 patients with pituitary adenomas. The leading
      author (MB) operated pituitary adenomas via pure endoscopic endonasal
      transsphenoidal surgery between January 2006 and August 2011 at the Hacettepe
      University, Department of Neurosurgery in Ankara. Complications were assessed in
      624 surgical procedures under five groups; rhinological, CSF leaks, infection,
      vascular and endocrinologic complications. We observed a total of 76
      complications (12.1%). Rhinological complications occurred in 8 patients (1.3%):
      4 epistaxis (0.6%) and 4 hyposmia (0.6%). Postoperative CSF leaks occurred in 8
      patients (1.3%), and infectious complications occurred in 8 patients: 3 cases of
      sphenoidal sinusitis (0.4%), 5 cases of meningitis (0.8%). Only 1 case of
      internal carotid aneurysm rupture during the opening of sellar floor (0.16%) was
      observed. Endocrinologic complications occurred in 51 (8.1%) patients: Anterior
      pituitary deficiency in 12 (1.9%), transient diabetes insipidus (DI) in 29
      (4.6%), permanent DI in 3 (0.4%) and inappropriate antidiuretic hormone secretion
      syndrome occurred in 7 (1.1%). There was no mortality directly related to the
      surgical procedure. The complication rates observed in our study suggests that
      the endoscopic pituitary surgery is at least as safe as microscopic
      transphenoidal surgery. These rates were obtained with due experience and well
      coordinated teamwork. To further improve these rates, new technological
      developments will be helpful.

PMID- 22161545
TI  - Allosteric activation of kinases: design and application of RapR kinases.
AB  - Here we describe a method for the engineered regulation of protein kinases in
      living cells, the design and application of RapR (rapamycin regulated) kinases.
      The RapR kinase method enables activation of kinases with high specificity and
      precise temporal control. Insertion of an engineered allosteric switch, the iFKBP
      domain, at a structurally conserved position within the kinase catalytic domain
      makes the modified kinase inactive. Treatment with rapamycin or its non
      immunosuppressive analogs triggers interaction with a small FKBP-rapamycin
      binding domain (FRB), restoring the activity of the kinase. The reagents used in
      this method are genetically encoded or membrane permeable, enabling ready
      application in many systems. Based on the structural similarity of kinase
      catalytic domains, this method is likely applicable to a wide variety of kinases.
      Successful regulation has already been demonstrated for three kinases
      representing both tyrosine and serine/threonine kinase families (p38, FAK, Src).
      Procedures for designing and testing RapR kinases are discussed.

PMID- 22161546
TI  - Interaction trap/two-hybrid system to identify interacting proteins.
AB  - The yeast two-hybrid method (or interaction trap) is a powerful technique for
      detecting protein interactions. The procedure is performed using transcriptional
      activation of a dual reporter system in yeast to identify interactions between a
      protein of interest (the bait protein) and the candidate proteins for
      interaction. The method can be used to screen a protein library for interactions
      with a bait protein or to test for association between proteins that are expected
      to interact based on prior evidence. Interaction mating facilitates the screening
      of a library with multiple bait proteins.

PMID- 22161544
TI  - Genetically engineered mesenchymal stem cells as a proposed therapeutic for
      Huntington's disease.
AB  - There is much interest in the use of mesenchymal stem cells/marrow stromal cells
      (MSC) to treat neurodegenerative disorders, in particular those that are fatal
      and difficult to treat, such as Huntington's disease. MSC present a promising
      tool for cell therapy and are currently being tested in FDA-approved phase I-III
      clinical trials for many disorders. In preclinical studies of neurodegenerative
      disorders, MSC have demonstrated efficacy, when used as delivery vehicles for
      neural growth factors. A number of investigators have examined the potential
      benefits of innate MSC-secreted trophic support and augmented growth factors to
      support injured neurons. These include overexpression of brain-derived
      neurotrophic factor and glial-derived neurotrophic factor, using genetically
      engineered MSC as a vehicle to deliver the cytokines directly into the
      microenvironment. Proposed regenerative approaches to neurological diseases using
      MSC include cell therapies in which cells are delivered via intracerebral or
      intrathecal injection. Upon transplantation, MSC in the brain promote endogenous
      neuronal growth, encourage synaptic connection from damaged neurons, decrease
      apoptosis, reduce levels of free radicals, and regulate inflammation. These
      abilities are primarily modulated through paracrine actions. Clinical trials for
      MSC injection into the central nervous system to treat amyotrophic lateral
      sclerosis, traumatic brain injury, and stroke are currently ongoing. The current
      data in support of applying MSC-based cellular therapies to the treatment of
      Huntington's disease is discussed.

PMID- 22161547
TI  - Methods for growing and titrating African swine fever virus: field and laboratory
      samples.
AB  - Growing African swine fever virus (ASFV) isolates obtained mainly from the field,
      but also engineered in the laboratory, is a critical step for diagnosis,
      titration, or virus infection studies. This unit describes a set of methods and
      protocols to produce and titrate any ASFV strain in cell cultures. The procedures
      include (1) basic techniques to prepare virus-sensitive target cells; (2)
      strategies for growth, concentration, and purification of virus stocks; and (3)
      the semi-quantitative (end dilution) and quantitative (plaque) assays for the
      determination of viral titers, and the use of different ASFV-sensitive cells as
      targets for virus production and titration.

PMID- 22161548
TI  - Analyzing integrin-dependent adhesion.
AB  - In this unit, methods for the analysis of integrin-dependent adhesion are
      described. Two major types of assays are commonly used for this analysis. The
      first are cell adhesion assays (as described in UNIT 9.1). A key application of
      this type of assay is to identify which integrin(s) mediate cell-substrate
      interactions; a comprehensive list of antibodies suitable for this purpose is
      detailed. The second are solid-phase assays in which purified integrins and
      integrin ligands are used. These assays can be used, e.g., to measure apparent
      affinities of integrins for different ligands and IC(50) values of
      pharmacological inhibitors.

PMID- 22161549
TI  - Comparison of NMR lipid profiles in mitotic arrest and apoptosis as indicators of
      paclitaxel resistance in cervical cell lines.
AB  - This study aimed to characterize changes in lipid saturation using magnetic
      resonance spectroscopy of sensitive (HeLa) and resistant (C33A; Me180) cervical
      cancer cell lines following exposure to paclitaxel to explore lipid profiles as
      biomarkers of drug resistance. Spectra were acquired at 11.74 T. Flow cytometry,
      electron, and confocal microscopy assessed cellular morphology. Western blots
      assessed cytoplasmic phospholipase A(2) , fatty acid synthase, and acyl-CoA
      synthetase1 expression. After 24 h of paclitaxel exposure, >60% of cells showed
      mitotic arrest. At 48 h, HeLa cells showed apoptosis while C33A/Me180 cells
      showed normal morphology indicating resistance. MR-visible lipids increased
      significantly in all lines at 24 h with further increases at 48 h; resistant
      lines showed smaller increases than HeLa. Cytoplasmic phospholipase A(2) and
      fatty acid synthase levels were unchanged at 24 h and dropped at 48 h in HeLa;
      acyl-CoA synthetase1 was higher in Me180/C33A than in HeLa controls but did not
      increase significantly. The percentage of cells displaying lipid droplets
      increased significantly at 24 and 48 h in all lines; droplet size increased only
      in HeLa cells. Droplet number was >3-4* greater in apoptotic compared with
      mitotic-arrested cells. Apoptotic cells accumulate unsaturated fatty acids in
      large (relative to control) droplets; resistant lines accumulated smaller
      droplets with less triglycerides.

PMID- 22161550
TI  - Chemotherapy with modified docetaxel, cisplatin, and 5-fluorouracil in patients
      with metastatic head and neck cancer.
AB  - INTRODUCTION: This retrospective study evaluates the efficacy of palliative
      chemotherapy with a modified docetaxel, cisplatin, 5-fluorouracil (5-FU; "TPF"
      regimen) regimen (mTPF; reduced doses of docetaxel, cisplatin, and 5-FU with
      reduction of intravenous 5-FU from 4 days to 2 days) in Asian patients with
      recurrent and metastatic squamous cell carcinoma of head and neck (HNSCC) after
      surgery and adjuvant chemoradiation. METHODS: The mTPF regimen was used in this
      study. Fifty-five patients (from January 2007 to October 2009) received docetaxel
      on day 1, followed by cisplatin and 5-FU administered continuous infusion on day
      2 for another 48 hours every 3 weeks for three to six cycles. RESULTS: The
      disease control rate was 81%. The overall response rate was 56%. Five patients
      achieved complete remission; 26 patients had partial remission; 14 patients had
      stable disease. Ten patients had disease progression. The metastatic sites that
      responded well to mTPF regimen (either complete or partial remission) were: neck
      lymph node, lung, liver, and skin. The median follow-up was 15 months (range 1-28
      months). The median overall survival was 10 months (range 2-28 months). The
      common nonhematological toxicity was alopecia and the most common hematological
      adverse event was neutropenia. Thirty-one patients (56%) had grade 3-4
      neutropenia. CONCLUSION: The mTPF chemotherapy regimen is efficacious for the
      palliative treatment of recurrent and metastatic HNSCC in Asian patients.

PMID- 22161551
TI  - Potential toxic effects of iron oxide nanoparticles in in vivo and in vitro
      experiments.
AB  - The aim of this study was to determine the potential toxic effects of
      iron(II,III)oxide nanoparticles (IONPs). In in vivo experiments, the toxic
      effects of IONPs were monitored in adult male Wistar rats by morphological
      methods after a single intratracheal instillation. For the control group 1 ml of
      physiological saline per animal was given, and the treatment group received the
      same volume of a suspension containing 1 and 5 mg kg-1 body weight IONPs. Lungs
      and internal organs underwent histopathological examination after 1, 3, 7, 14 and
      30 days. The mutagenic effect of these nanoparticles was evaluated by the
      bacterial reverse mutation assay on Salmonella typhimurium TA98, TA100, TA1535
      and TA1537 strains, and on Escherichia coli WP2uvrA strain, in the presence and
      absence of the mammalian metabolic activation system S9. The in vitro cytotoxic
      effect of IONPs was also examined in Vero cells after short-term (4 h) and long
      term (24 h) exposure. There were no pathological changes in examined internal
      organs, except a very weak pulmonary fibrosis developing by the end of the first
      month in the treated rats. While in vitro MTT assay showed a moderate cytotoxic
      effect, IONPs proved to be devoid of mutagenic effect in the bacterial systems
      tested. The results may be a useful extension of our knowledge on the safety of
      magnetite nanoparticles in view of their possible medical applications, such as
      in hyperthermia and magnetic resonance imaging.

PMID- 22161553
TI  - [Abdominal ultrasound: clinically important and relevant for the future].

PMID- 22161552
TI  - Exposure to oral bisphosphonates and risk of cancer.
AB  - Recently, oral bisphosphonate use has increased markedly in the United States and
      elsewhere. Little is known about cancer risks associated with these drugs. A few
      studies have observed associations between bisphosphonates and the risk of
      breast, colorectal and esophageal cancer. However, the risk of all cancer and the
      risk of other cancers have not been investigated. In our study, we examined the
      risk of all cancer and site specific cancers in individuals taking
      bisphosphonates. Data were extracted from the UK General Practice Research
      Database to compare site-specific cancer incidence in a cohort of oral
      bisphosphonate users and a control cohort. Hazard ratios (HRs) were calculated
      using Cox regression modeling. The bisphosphonate and control cohort contained
      41,826 participants (mean age 70, 81% female). Overall, the bisphosphonate cohort
      compared with the control cohort had a reduced risk of all cancer after any
      bisphosphonate usage [HR=0.87, 95% confidence interval (CI) 0.82, 0.92]. In the
      bisphosphonate cohort, compared with the control cohort, there was no evidence of
      a difference in the risk of lung (HR=1.03, 95% CI 0.88, 1.20) or prostate cancer
      (HR=0.86, 95% CI 0.67, 1.09) but breast (HR=0.71, 95% CI 0.62, 0.81) and
      colorectal cancer (HR=0.74, 95% CI, 0.60-0.91) were both reduced. Our findings
      indicate that bisphosphonates do not appear to increase cancer risk. Although
      reductions in breast and colorectal cancer incidence were observed in
      bisphosphonate users it is unclear, particularly for breast cancer, to what
      extent confounding by low bone density may explain the association.

PMID- 22161554
TI  - Ultrasound in portal hypertension--part 1.

PMID- 22161555
TI  - Incidentally detected splenic lesions in ultrasound: does contrast-enhanced
      ultrasonography improve the differentiation of benign hemangioma/hamartoma from
      malignant lesions?
AB  - PURPOSE: The aim of the study was to identify and validate enhancing features for
      differentiating benign vascular neoplasms of the hemangioma/hamartoma type from
      malignant splenic lesions on contrast-enhanced ultrasonography (CEUS). MATERIALS
      AND METHODS: 136 splenic lesions (58 benign vascular neoplasms, 78 malignant) in
      136 patients underwent baseline US and pulse-inversion CEUS after sulfur
      hexafluoride-filled microbubble injection. Two on-site readers assessed lesion
      enhancement features during arterial and parenchymal phase in consensus. Best
      predicting CEUS features for lesion diagnosis were identified through univariate
      and multivariate analyses. Two blinded off-site readers independently issued a
      confidence rating for lesion diagnosis in baseline US and CEUS using extracted
      diagnostic CEUS features. Diagnostic performance, receiver operating curves (Az
      value), and interreader agreement were calculated. The reference standards were
      histopathology or CT and/or MR imaging with clinical follow-up.  RESULTS:
      Multivariate analysis outlined arterial hyperenhancement or isoenhancement to be
      an independent CEUS predictor of benign vascular neoplasms (odds ratio, 3.558; p
      < 0.0017). Within the subgroup of isoechoic or hypoechoic lesions, arterial
      hyperenhancement was virtually diagnostic for benign vascular neoplasm (odds
      ratio, 21.333; p < 0.001). The diagnostic accuracy and confidence (Az-value) of
      the two readers was 63.2 % and 70.6 % (0.785 and 0.818) for baseline US, which
      improved significantly to 87.5 % and 88.2 % (0.915 and 0.908) for CEUS (p <
      0.001). Interreader agreement also increased with CEUS (? = 0.88) compared to
      baseline US (? = 0.52). CONCLUSION: Sulfur hexafluoride-enhanced CEUS improves
      differentiation between benign vascular and malignant splenic tumors and may be
      especially useful in clinical scenarios in which the incidental hypoechoic
      splenic lesion is unclear on conventional US.

PMID- 22161556
TI  - Diagnostic accuracy of CEUS in the differential diagnosis of small (<= 20  mm)
      and subcentimetric (<= 10  mm) focal liver lesions in comparison with histology.
      Results of the DEGUM multicenter trial.
AB  - PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced ultrasound
      (CEUS) in the differential diagnosis of small and subcentimetric liver tumors in
      clinical practice. MATERIALS AND METHODS: 1349 patients with a hepatic tumor
      lacking a definite diagnosis based on B-mode ultrasound and power Doppler
      ultrasound were examined at 14 hospitals by CEUS using a standardized protocol
      (pulse/phase inversion imaging, mechanical index < 0.4). Differential diagnosis
      was based on the vascularity pattern and contrast enhancement pattern during the
      arterial, portal, and late phase according to the EFSUMB guidelines. 335 patients
      with focal liver lesions (FLL) <= 20  mm were analyzed. The tumor status
      established after CEUS was compared to histology (73.2 %) or in some cases to CT
      or MRI. RESULTS: A definitive diagnosis based on the gold standard was possible
      in 329 FLLs, while 6 FLLs remained unclear even in the combined gold standard
      (histology and/or CT and/or MRI). The final diagnoses of <= 20  mm FLL with
      histological confirmation (n = 241) included 87 benign and 154 malignant
      entities. The overall diagnostic accuracy of CEUS in FLL <= 20  mm with
      histological confirmation was 83.8 %. CEUS correctly identified 144 /154
      malignant FLLs (sensitivity 93.5 %) and 58 /87 benign FLLs (specificity 66.7 %).
      24 /241 FLLs remained unclear after CEUS (9.9 %). CEUS misclassified 15 /241 FLLs
      (6.2 %; 12 benign and 3 malignant FLLs). The positive predictive value of CEUS
      for a malignant FLL was 92.3 % and the negative predictive value was 95.1 %. Out
      of 241 small FLLs with histological confirmation, 62  FLLs were <= 10  mm
      (diagnostic accuracy of CEUS 80.6 %) and 179 FLLs were > 10  mm and <= 20  mm
      (diagnostic accuracy of CEUS 84.9 %). CONCLUSION: CEUS has a high diagnostic
      accuracy for the differential diagnosis of small and subcentimetric FLLs in
      clinical practice.

PMID- 22161557
TI  - Frequency of tumor entities among liver tumors of unclear etiology initially
      detected by sonography in the noncirrhotic or cirrhotic livers of 1349 patients.
      Results of the DEGUM multicenter study.
AB  - AIM: Investigation of the frequency of various solid focal liver lesions (SFLL)
      in noncirrhotic and cirrhotic livers with focus on the frequency of metastasis in
      cirrhotic livers. MATERIAL AND METHODS: The patient collective in the DEGUM
      multicenter study (n = 1349) was reevaluated and divided in subcollective A
      without (n = 1067) and B with cirrhosis (n = 282). 74.6 % of the various tumor
      entities were confirmed histologically (n = 1006). RESULTS: In subcollective A
      there were 385 patients with metastases (36.4 %) and 65 with HCC (6.1 %), whereas
      the most common benign lesions were hemangioma, with 237 cases (22.4 %) and FNH,
      with 170 cases (16.1 %). In subcollective B there were 216 cases of HCC (76.6 %)
      and 12 metastases (4.3 %), as well as 42 benign lesions (14.9 %). CCC was rare in
      both subcollective A (3.3 %) and subcollective B (2.5 %). A positive oncological
      history increased the probability of a malignant SFLL in subcollective A by 1.8
      times, but did not do so in subcollective B. CONCLUSION: The frequency of various
      tumor entities is different in patients with and without cirrhosis of the liver.
      In noncirrhotic livers, malignant and benign SFLL are equally common. The most
      common forms are metastases, hemangiomas and FNH, CCC is rare. A positive history
      of extrahepatic malignancy increases the probability of a malignant SFLL. In
      cirrhosis, HCC dominates, HCC is 18 times as common as metastases. Benign SFLL
      and CCC are rare.

PMID- 22161558
TI  - Hypothesis: human umbilical cord blood-derived stromal cells regulate the Foxp3
      expression of regulatory T cells through the TGF-beta1/Smad3 pathway.
AB  - Despite the improvements in transplant immunology and clinical and supportive
      care, graft-versus-host disease (GVHD) is still among the most common causes of
      overall mortality and morbidity after allogeneic hematopoietic cell
      transplantation. The development and severity of GVHD are strongly related with
      post-transplant outcomes. New strategies should be explored to overcome GVHD.
      Regulatory T cells (Treg cells), as dedicated suppressors of diverse immune
      responses and inflammation and important gatekeepers of immune homeostasis,
      contribute to the prevention of graft rejection and induce transplantation
      tolerance. Foxp3, a transcription factor, is predominantly expressed in Treg
      cells and is a master regulator of the development and function of Treg cells.
      Foxp3 mutations and Foxp3 deficiency lead to lethal autoimmune
      lymphoproliferative disease, which results from a defect in Treg cells. TGF-beta1
      is required to maintain Foxp3 expression in Treg cells. We isolated a novel
      population from among CD34(+) cells in our laboratory, referred to as human
      umbilical cord blood-derived stromal cells (hUCBDSCs), which exert an
      immunosuppressive effect and can notably increase Foxp3 expression in Treg cells.
      Our previous study also revealed that hUCBDSCs constantly secrete TGF-beta1.
      Based on the literature searchings and our experimental findings, we hypothesize
      that hUCBDSCs, which secrete a high level of TGF-beta1, modulate the Foxp3
      expression of Treg cells through the TGF-beta1/Smad3 pathway to regulate GVHD.

PMID- 22161559
TI  - Color compensation in nitrite-reduced meat batters incorporating paprika or
      tomato paste.
AB  - BACKGROUND: Nitrite is a key ingredient the manufacture of meat products, forming
      a stable pink color characteristic of cured products, retarding the development
      of rancidity and off-odors and flavors during storage, and preventing microbial
      growth. The negative aspects of nitrite and the demands for healthy foods result
      in the need to reduce nitrite in cured meat products. Paprika or tomato has been
      employed as natural pigments in meat products. The objective of this work was to
      determine the effect of incorporating paprika powder or tomato paste on the
      texture, rancidity and instrumental and sensory color compensation in nitrite
      reduced meat batters. RESULTS: Addition of tomato paste improved moisture
      content, resulting in harder but less cohesive samples as compared to control and
      paprika-containing meat batters. Color characteristics of reduced nitrite samples
      obtained higher a* red coloration (8.9 for paprika and 7.7-8.0 for tomato paste),
      as compared to control samples (5.65). Instrumental color was low in control
      samples, with high values for tomato paste and paprika samples. Nonetheless,
      tomato paste used to compensate color in nitrite-reduced meat batters was ranked
      closer to the control sample in sensory evaluation. CONCLUSION: Color
      characteristics-instrumental and sensory-in these kinds of meat products were
      enhanced by the addition of 2.5-3.0% of tomato paste, presenting results close to
      the non-reduced nitrite control. Similarly, antioxidant components of tomato
      paste or paprika reduced lipid oxidation. Nitrite reduction from 150 to 100 ppm
      could be achieved employing tomato paste as a natural pigment to improve color
      and texture.

PMID- 22161560
TI  - Suppression of immunodeficiency virus-associated neural damage by the p75
      neurotrophin receptor ligand, LM11A-31, in an in vitro feline model.
AB  - Feline immunodeficiency virus (FIV) infection like human immunodeficiency virus
      (HIV), produces systemic and central nervous system disease in its natural host,
      the domestic cat, that parallels the pathogenesis seen in HIV-infected humans.
      The ability to culture feline nervous system tissue affords the unique
      opportunity to directly examine interactions of infectious virus with CNS cells
      for the development of models and treatments that can then be translated to a
      natural infectious model. To explore the therapeutic potential of a new p75
      neurotrophin receptor ligand, LM11A-31, we evaluated neuronal survival, neuronal
      damage and calcium homeostasis in cultured feline neurons following inoculation
      with FIV. FIV resulted in the gradual appearance of dendritic beading, pruning of
      processes and shrinkage of neuronal perikarya in the neurons. Astrocytes
      developed a more activated appearance and there was an enhanced accumulation of
      microglia, particularly at longer times post-inoculation. Addition of 10 nM LM11A
      31, to the cultures greatly reduced or eliminated the neuronal pathology as well
      as the FIV effects on astrocytes and microglia. LM11A-31 also, prevented the
      development of delayed calcium deregulation in feline neurons exposed to
      conditioned medium from FIV treated macrophages. The suppression of calcium
      accumulation prevented the development of foci of calcium accumulation and
      beading in the dendrites. FIV replication was unaffected by LM11A-31. The strong
      neuroprotection afforded by LM11A-31 in an infectious in vitro model indicates
      that LM11A-31 may have excellent potential for the treatment of HIV-associated
      neurodegeneration.

PMID- 22161561
TI  - Global hypothesis testing for high-dimensional repeated measures outcomes.
AB  - High-throughput technology in metabolomics, genomics, and proteomics gives rise
      to high dimension, low sample size data when the number of metabolites, genes, or
      proteins exceeds the sample size. For a limited class of designs, the classic
      'univariate approach' for Gaussian repeated measures can provide a reasonable
      global hypothesis test. We derive new tests that not only accurately allow more
      variables than subjects, but also give valid analyses for data with complex
      between-subject and within-subject designs. Our derivations capitalize on the
      dual of the error covariance matrix, which is nonsingular when the number of
      variables exceeds the sample size, to ensure correct statistical inference and
      enhance computational efficiency. Simulation studies demonstrate that the new
      tests accurately control Type  I error rate and have reasonable power even with a
      handful of subjects and a thousand outcome variables. We apply the new methods to
      the study of metabolic consequences of vitamin B6 deficiency. Free software
      implementing the new methods applies to a wide range of designs, including one
      group pre-intervention and post-intervention comparisons, multiple parallel group
      comparisons with one-way or factorial designs, and the adjustment and evaluation
      of covariate effects.

PMID- 22161562
TI  - Plastic bronchitis 3 years after Fontan palliation.

PMID- 22161563
TI  - Pneumopericardium as a rare complication of continuous positive airway pressure
      in spontaneously breathing neonates.

PMID- 22161565
TI  - Using QIIME to analyze 16S rRNA gene sequences from microbial communities.
AB  - QIIME (canonically pronounced "chime") is a software application that performs
      microbial community analysis. It is an acronym for Quantitative Insights Into
      Microbial Ecology, and has been used to analyze and interpret nucleic acid
      sequence data from fungal, viral, bacterial, and archaeal communities. The
      following protocols describe how to install QIIME on a single computer and use it
      to analyze microbial 16S sequence data from nine distinct microbial communities.

PMID- 22161566
TI  - An introduction to the informatics of "next-generation" sequencing.
AB  - Next-generation sequencing (NGS) packs the sequencing throughput of a 2000's-era
      genome center into a single affordable machine. However, software developed for
      conventional sequencing technologies is often inadequate to deal with the nature
      of NGS technologies, which produce short, massively parallel reads. This unit
      surveys the software packages that are available for managing and analyzing NGS
      data.

PMID- 22161564
TI  - MicroRNAs in trees.
AB  - MicroRNAs (miRNAs) are 20-24 nucleotide long molecules processed from a specific
      class of RNA polymerase II transcripts that mainly regulate the stability of
      mRNAs containing a complementary sequence by targeted degradation in plants. Many
      features of tree biology are regulated by miRNAs affecting development,
      metabolism, adaptation and evolution. MiRNAs may be modified and harnessed for
      controlled suppression of specific genes to learn about gene function, or for
      practical applications through genetic engineering. Modified (artificial) miRNAs
      act as dominant suppressors and are particularly useful in tree genetics because
      they bypass the generations of inbreeding needed for fixation of recessive
      mutations. The purpose of this review is to summarize the current status of
      information on miRNAs in trees and to guide future studies on the role of miRNAs
      in the biology of woody perennials and to illustrate their utility in directed
      genetic modification of trees.

PMID- 22161567
TI  - Identification of novel and known miRNAs in deep-sequencing data with miRDeep2.
AB  - miRNAs comprise an abundant class of small non-coding RNAs that play important
      roles in a wide range of biological processes by post-transcriptional regulation
      of a large fraction of animal genes. High-throughput sequencing machines and the
      availability of completely sequenced genomes make it possible to reliably
      identify miRNAs with computational methods. This unit documents how to use the
      miRDeep2 software package to identify novel and known microRNAs in small RNA deep
      sequencing data. Moreover, the usage of miRDeep2 to profile miRNA expression
      across samples is illustrated.

PMID- 22161568
TI  - Using the scan-x Web site to predict protein post-translational modifications.
AB  - The recent plethora of proteomic mass spectrometry data is providing evidence
      that almost every protein in the cell undergoes some form of post-translational
      modification. We describe a protocol to use the scan-x Web site to view predicted
      acetylation sites in the human proteome and predicted phosphorylation sites in
      the human, mouse, fly, and yeast proteomes with high specificity. This tool is
      accessible from virtually any computer with a Web browser. The only requirement
      is a means of searching for a protein of interest in one of the represented
      organisms.

PMID- 22161569
TI  - Installation and use of LabKey Server for proteomics.
AB  - LabKey Server (formerly CPAS, the Computational Proteomics Analysis System)
      provides a Web-based platform for mining data from liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) proteomic experiments. This open source platform
      supports systematic proteomic analyses and secure data management, integration,
      and sharing. LabKey Server incorporates several tools currently used in proteomic
      analysis, including the X! Tandem search engine, the ProteoWizard toolkit, and
      the PeptideProphet and ProteinProphet data mining tools. These tools and others
      are integrated into LabKey Server, which provides an extensible architecture for
      developing high-throughput biological applications. The LabKey Server analysis
      pipeline acts on data in standardized file formats, so that researchers may use
      LabKey Server with other search engines, including Mascot or SEQUEST, that follow
      a standardized format for reporting search engine results. Supported builds of
      LabKey Server are freely available at http://www.labkey.com/. Documentation and
      source code are available under the Apache License 2.0 at http://www.labkey.org.

PMID- 22161570
TI  - Analyzing molecular interactions.
AB  - Molecular interactions are key processes that drive the functions of molecules.
      Large data sets of protein interaction data are being assembled that will help
      analyze structural and functional aspects of interactions. This chapter
      introduces techniques for analyzing both the structural aspects of molecular
      interactions and methods to use this information to understand and define
      biological pathways.

PMID- 22161571
TI  - Characterization of the acylglycerols and resulting biodiesel derived from
      vegetable oil and microalgae (Thalassiosira pseudonana and Phaeodactylum
      tricornutum).
AB  - Algal biofuels are a growing interest worldwide due to their potential in terms
      of sustainable greenhouse gas displacement and energy production. This article
      describes a comparative survey of biodiesel production and conversion yields of
      biodiesel via alkaline transesterification of acylglycerols extracted from the
      microalgae Thalassiosira pseudonana and Phaeodactylum tricornutum, grown under
      silicate or nitrate limitation, and that of model vegetable oils: soybean, and
      rapeseed oil. Acylglycerols were extracted with n-hexane and the total yield per
      biomass was determined by gravimetric assay. Under our conditions, the total
      acylglycerol yield from the microalgae studied was 13-18% of total dry weight.
      The biodiesel samples were analyzed using gas chromatography-flame ionization
      detector to determine quantitative information of residual glycerol, mono-, di-,
      and tri-acylglycerol concentrations in the biodiesel. All of the algal-based
      biodiesel demonstrated less mono-, di-, and tri-acylglycerol concentrations than
      the vegetable-based biodiesel under identical transesterification conditions. The
      fatty acid compositions of all the feedstock oils and their resultant biodiesel
      were also analyzed and reported. Based on the fatty acid methyl ester
      compositions of our samples we qualitatively assessed the suitability of the
      algal-derived biodiesel in terms of cetane number (CN), cold-flow properties, and
      oxidative stability.

PMID- 22161573
TI  - Particles in therapeutic protein formulations, Part 1: overview of analytical
      methods.
AB  - The presence of particles is a major issue during therapeutic protein formulation
      development. Both proteinaceous and nonproteinaceous particles need to be
      analyzed not only due to the requirements of the Pharmacopeias but also to
      monitor the stability of the protein formulation. Increasing concerns about the
      immunogenic potential together with new developments in particle analysis make a
      comparative description of established and novel analytical methods useful. Our
      review aims to provide a comprehensive overview on analytical methods for the
      detection and characterization of visible and subvisible particles in therapeutic
      protein formulations. We describe the underlying theory, benefits, shortcomings,
      and illustrative examples for quantification techniques, as well as
      characterization techniques for particle shape, morphology, structure, and
      identity.

PMID- 22161574
TI  - Formation of y + 10 and y + 11 ions in the collision-induced dissociation of
      peptide ions.
AB  - Tandem mass spectra of peptide ions, acquired in shotgun proteomic studies of
      selected proteins, tissues, and organisms, commonly include prominent peaks that
      cannot be assigned to the known fragmentation product ions (y, b, a, neutral
      losses). In many cases these persist even when creating consensus spectra for
      inclusion in spectral libraries, where it is important to determine whether these
      peaks represent new fragmentation paths or arise from impurities. Using spectra
      from libraries and synthesized peptides, we investigate a class of fragment ions
      corresponding to y(n-1) + 10 and y(n-1) + 11, where n is the number of amino acid
      residues in the peptide. These 10 and 11 Da differences in mass of the y ion were
      ascribed before to the masses of [+ CO - H(2)O] and [+ CO - NH(3)], respectively.
      The mechanism is suggested to involve dissociation of the N-terminal residue at
      the CH-CO bond following loss of H(2)O or NH(3). MS(3) spectra of these ions show
      that the location of the additional 10 or 11 Da is at the N-terminal residue. The
      y(n-1) + 10 ion is most often found in peptides with N-terminal proline,
      asparagine, and histidine, and also with serine and threonine in the adjacent
      position. The y(n-1) + 11 ion is observed predominantly with histidine and
      asparagine at the N-terminus, but also occurs with asparagine in positions two
      through four. The intensities of the y(n-1) + 10 ions decrease with increasing
      peptide length. These data for y(n-1) + 10 and y(n-1) + 11 ion formation may be
      used to improve peptide identification from tandem mass spectra.

PMID- 22161575
TI  - Preliminary demonstration of an IonCCD as an alternative pixelated anode for
      direct MCP readout in a compact MS-based detector.
AB  - We report on the preliminary testing of a new position-sensitive detector (PSD)
      by combining a microchannel plate (MCP) and a charge-sensitive pixilated anode
      with a direct readout based on charge-coupled detector (CCD) technology, which
      will be referred to as IonCCD (Hadjar et al. J Am Soc Mass Spectrom 22(4):612
      623, 2011; Johnson et al. J Am Soc Mass Spectrom 22(8):1388-1394, 2011; Hadjar et
      al. J Am Soc Mass Spectrom 22(10):1872-1884, 2011). This work exploits the
      recently discovered electron detection capability of the IonCCD (Hadjar et al. J
      Am Soc Mass Spectrom 22(4):612-623, 2011), allowing it to be used directly behind
      an MC. This MCP-IonCCD configuration potentially obviates the need for electro
      optical ion detector systems (EOIDs), which typically feature a relatively
      difficult-to-implement 5-kV power source as well as a phosphorus screen behind
      the MCP for conversion of electrons to photons prior to signal generation in a
      photosensitive CCD. Thus, the new system (MCP-IonCCD) has the potential to be
      smaller, simpler, more robust, and more cost efficient than EOID-based
      technologies in many applications. The use of the IonCCD as direct MCP readout
      anode, as opposed to its direct use as an ion detector, will benefit from the
      instant three-to-four-order-of-magnitude gain of the MCP with virtually no
      additional noise. The signal/noise gain can be used for either sensitivity or
      speed enhancement of the detector. The speed enhancement may motivate the
      development of faster IonCCD readout speeds (currently at 2.7 ms) to achieve the
      2 kHz frame rate for which the IonCCD chip was designed, a must for transient
      signal applications. The presented detector exhibits clear potential not only as
      a trace analysis detector in scan-free mass spectrometry and electron
      spectroscopy but also as a compact detector for photon and particle imaging
      applications.

PMID- 22161576
TI  - Detection of osteoarthritis in knee and hip joints by fast field-cycling NMR.
AB  - It is known that in the early stages of osteoarthritis, the concentration of
      glycan proteins decreases in articular cartilage. This phenomenon is under active
      research to develop a means to characterize osteoarthritis accurately in the
      early stages of the disease, when still reversible. However, no method of
      quantification has yet shown clear success in this area. In this article, we
      propose a novel approach to detect glycan depletion using fast field-cycling NMR.
      This technique was previously reported to allow noninvasive measurement of
      protein concentration via the (14)N quadrupolar relaxation in certain amide
      groups. We have demonstrated that the articular cartilage exhibits clear
      quadrupolar peaks that can be measured by a benchtop fast field-cycling NMR
      device and which changes significantly between normal and diseased tissues (P <
      0.01). This signal is probably glycan specific. The method may have potential for
      early evaluation of osteoarthritis in patients on fast field-cycling-MRI scanners
      currently under evaluation in the authors' laboratory.

PMID- 22161577
TI  - A C-terminal tyrosine-based motif in the bile salt export pump directs clathrin
      dependent endocytosis.
AB  - The liver-specific bile salt export pump (BSEP) is crucial for bile acid
      dependent bile flow at the apical membrane. BSEP, a member of the family of
      structurally related adenosine triphosphate (ATP)-binding cassette (ABC)
      proteins, is composed of 12 transmembrane segments (TMS) and two large
      cytoplasmic nucleotide-binding domains (NBDs). The regulation of trafficking of
      BSEP to and from the cell surface is not well understood, but is believed to play
      an important role in cholestatic liver diseases such as primary familial
      intrahepatic cholestasis type 2 (PFIC2). To address this issue, BSEP endocytosis
      was studied by immunofluorescence and a cell surface enzyme-linked immunosorbent
      assay (ELISA) endocytosis reporter system using a chimera of the interleukin-2
      receptor alpha (previously referred to as Tac) and the C-terminal tail of BSEP
      (TacCterm). An autonomous endocytosis motif in the carboxyl cytoplasmic terminus
      of BSEP was identified. We define this endocytic motif by site-directed
      mutagenesis as a canonical tyrosine-based motif (1310) YYKLV(1314) (YxxO). When
      expressed in HEK293T cells, TacCterm is constitutively internalized via a dynamin
      and clathrin-dependent pathway. Mutation of the Y(1310) Y(1311) amino acids in
      TacCterm and in full-length human BSEP blocks the internalization. Subsequent
      sequence analysis reveals this motif to be highly conserved between the closely
      related ABCB subfamily members that mediate ATP-dependent transport of broad
      substrate specificity. CONCLUSION: Our results indicate that constitutive
      internalization of BSEP is clathrin-mediated and dependent on the tyrosine-based
      endocytic motif at the C-terminal end of BSEP.

PMID- 22161578
TI  - Early neonatal outcome in late preterms.
AB  - OBJECTIVES: To study the maternal risk factors, morbidity, mortality of late
      preterm in comparison to term neonates. METHODS: This Cohort study involved two
      hundred fifty consecutively born late preterm and equal number of term newborns
      delivered in a tertiary care hospital. They were followed till discharge for
      morbidities and mortality. Detailed maternal and neonatal factors were studied
      and compared between the two groups. RESULTS: Late preterm babies constituted 55%
      of all live preterm births during the study period. The odds of babies developing
      major morbidity was significantly more in those whose mothers had hypertension
      and infections (OR 2.69 95% CI: 1.55, 4.68 and 2.08, 95% CI: 1.6, 2.71
      respectively). In the study group, 42.4% and 20.8% babies suffered major and
      minor morbidity compared to 8.4% and 6.8% of term controls respectively. Late
      preterm neonates had significantly higher odds of developing morbidity like
      respiratory distress (12.4% vs. 5.6%, OR 2.21, 95%CI 1.21,4.11), need for non
      invasive(17.3% vs. 5.7%, OR 3.05 95% CI 1.69, 5.47) and invasive ventilation
      (14.6% vs. 1.7%, OR 8.62, 95% CI 3.09, 24.04), sepsis (20.8% vs. 5.2%, OR 5.20,
      95% CI 2.71, 9.99), seizures (22.8% vs. 4.8%, OR 4.75 95%CI 2.61, 8.63), shock
      (17.6% vs. 4.4%, OR 4.00 95% CI 2.12,7.56), and jaundice (26% vs. 6%, OR 4.33
      95%CI 2.54, 7.39). By logistic regression, the odds of developing major morbidity
      decreased with increasing gestational age (aOR 0.28 95% CI 0.18, 0.45; p < 0.001)
      and increased with hypertensive disease of pregnancy (aOR 2.16 95% CI 1.09,
      4.260; p = 0.026). CONCLUSIONS: Late preterm neonates have significantly more
      mortality and morbidity compared to term controls. Maternal hypertension and
      lower gestational age are the strongest predictors of morbidity.

PMID- 22161579
TI  - Endosulfan poisoning resulting from skin exposure.

PMID- 22161580
TI  - Reversible, unilateral dilatation of upper urinary tract due to a tight waist
      string.

PMID- 22161581
TI  - Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon: successful
      treatment with vincristine and ticlopidine.

PMID- 22161582
TI  - Clinical suspicion of Maturity Onset of Diabetes of the Young in pediatric
      patients diagnosed with diabetes mellitus.
AB  - Type 1 diabetes remains the predominant form of diabetes in the pediatric
      population, while the incidence of type 2 diabetes has increased, paralleling the
      increase in obesity. Another form of diabetes, Maturity Onset Diabetes of the
      Young (MODY), should also be considered especially in those whose clinical
      presentation is atypical for type 1 and type 2 diabetes. Although testing for
      MODY is a challenge, testing in appropriate patients and family members should be
      standard of care. Knowledge of the genetic etiology of the type of diabetes will
      enable appropriate treatment and optimize outcomes, allow more accurate
      prediction of disease progression, as well as allow screening for and the
      diagnosis of MODY in family members.

PMID- 22161583
TI  - Congestive heart failure: an uncommon presentation of systemic onset juvenile
      idiopathic arthritis (SOJIA).
AB  - Children with systemic onset Juvenile idiopathic arthritis (SOJIA) are known to
      develop myocarditis and congestive heart failure as a complication of disease
      process infrequently. Cardiac involvement causing congestive heart failure as a
      presenting manifestation in SOJIA is rarely described in the literature. The
      authors describe a case of an 11- yr- old boy with SOJIA who presented with
      congestive heart failure following active myocarditis, with the flare of the
      disease process. The cardiac manifestations, along with the disease activity were
      controlled with intensive immunosuppressive therapy.

PMID- 22161584
TI  - End products of lipid peroxidation in erythrocyte membranes in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is accompanied by oxidative stress in the brain. Because
      the brain tissue is rich in polyunsaturated fatty acids, it is prone to the free
      radical attack resulting in lipid peroxidation. Intermediates of lipid
      peroxidation may diffuse from the primary site, cross the blood-brain barrier and
      modify erythrocyte membranes in the bloodstream. We exposed isolated erythrocyte
      membranes from patients with AD and the control group to in vitro free radical
      damage and monitored the accumulation of the end products of lipid peroxidation,
      lipofuscin-like pigments (LFPs), by fluorescence spectroscopy. LFPs were analyzed
      by means of tridimensional and synchronous fluorescence spectroscopy. The levels
      of LFP formed during in vitro peroxidation were significantly higher in
      erythrocyte membranes from patients with AD compared with the control group.
      Furthermore, the chemical composition of LFP in AD was different from the control
      group. The analysis of the specific modifications of erythrocyte membranes in AD
      is of great medical importance regarding the need of a diagnostic blood
      biomarker.

PMID- 22161611
TI  - Real-time elastography of hepatic thermal lesions in vitro: histopathological
      correlation.
AB  - PURPOSE: To evaluate the reliability of elastography, a new ultrasonographic
      method, for delineating thermal lesion boundaries in porcine liver tissue by
      comparing lesion dimensions determined by real-time elastography with the
      findings at gross pathology. MATERIALS AND METHODS: A total of 15 thermal lesions
      with diameters ranging from 17 to 60 mm were created using radiofrequency
      ablation (RFA). Color-coded elastography was performed by one experienced
      examiner, using a 6 - 15 MHz high frequency linear transducer (LOGIQ E9, GE).
      Lesions were examined using B-mode and real-time elastography (RTE). Lesion
      detection, delineation and size were assessed using B-mode and RTE immediately
      after each thermal ablation ( < 5 min). Measurements of the sections representing
      the same image plane used for elastography were taken during pathologic
      examination and compared to the measurements obtained from the elastograms.
      RESULTS: In our sample a statistically significant correlation in vitro between
      RTE and pathological measurements with respect to the lesion's principal axis and
      area (r2 = 0.9338 long axis, r2 = 0.8998 short axis and r2 = 0.9676 area) was
      found. Overall, elastography slightly underestimated the lesion size, as judged
      by the digitalized pathologic images. CONCLUSION: These results support that RTE
      outperforms conventional B-mode ultrasound and could potentially be used for the
      routine assessment of thermal therapies.

PMID- 22161612
TI  - Role of ultrasonography in the diagnosis and follow-up of pediatric eosinophilic
      gastroenteritis: a case report and review of the literature.
AB  - Eosinophilic gastroenteritis (EG) is a rare disease characterized by the
      infiltration of one or more layers of the digestive tract by eosinophilic
      leukocytes. The diagnosis is confirmed by histological examination of a
      characteristic biopsy, but radiological features are useful for diagnostic
      suspicion. We report the case of an adolescent boy with recurrent epigastric
      pain, nausea and vomiting, in whom sonographic features and eosinophilia of the
      peripheral blood suggested the diagnosis of EG. Moreover, we reviewed the
      radiological features of EG with particular regard to the role of sonography in
      the diagnosis and follow-up of EG, especially in children. We emphasize the
      utility of sonography in pediatric patients presenting with gastrointestinal
      symptoms, since it may provide useful information in a quick, inexpensive and
      noninvasive way. Ultrasonographic detection of features such as bowel wall
      thickness, ascites and peritoneal nodules may be largely suggestive of EG and may
      prevent other invasive exams and abdominal surgery. Ultrasonography can also be
      easily used in the follow-up of these patients, and may obviate the frequent and
      potentially dangerous exposure to radiation.

PMID- 22161613
TI  - Punched nerve syndrome: ultrasonographic appearance of functional vascular nerve
      impairment.
AB  - PURPOSE: The mechanical impact of a neighboring vessel on a "punched" nerve
      segment is thought to be one possible cause of compression neuropathy but has not
      been proven definitively. We report on 9 subjects with unclear clinical
      mononeuropathies in whom we could clearly define peripheral nerve impairment by
      such vessels on real-time high-resolution ultrasound (HRUS). MATERIALS AND
      METHODS: Nine subjects with unclear mononeuropathy based on clinical neurological
      examination were referred to our department for HRUS assessment. The shape, inner
      and outer echotexture, size and diameter, and overall integrity of these nerves
      were assessed including an exact analysis of the surrounding soft tissues to
      search for potentially extraneural pathology. This included duplex imaging to
      identify even tiny atypical vascular structures. RESULTS: In all patients duplex
      HRUS showed the pulsatile and "punching" character of the relevant vessels and
      the direct mechanical impact of these vessel. The involved nerve segments
      appeared enlarged with a hypoechoic change of echotexture including at least
      partial masking of their inner fascicular texture. CONCLUSION: Although rare, a
      "punching" vessel can be the cause of a compression neuropathy. Therefore, duplex
      HRUS must be included in every HRUS examination of patients with otherwise
      unclear mononeuropathy.

PMID- 22161614
TI  - Intravenous application of second-generation ultrasound contrast agents in
      children: a review of the literature.
AB  - CEUS examinations using second-generation ultrasound contrast agents (UCA) are
      conducted in children, despite not being registered for individuals less than 18
      years of age. We searched the Medline(r) database through Pubmed(r) and Scopus
      database, in order to find articles in which UCA were administered intravenously
      in patients under the age of 18. We analyzed in detail 9 papers (7 case reports,
      2 original research studies), describing the examinations with intravenous
      administration of the UCA in children, and 23 original papers, in which the study
      group included at least one individual under the age of 18. Neither of the
      analyzed studies included any reports of adverse effects after UCA
      administration.

PMID- 22161615
TI  - Sonographic assessment of fetal cardiac function: indirect measurements of fetal
      cardiac function, newer techniques and clinical applications.
AB  - Noninvasive blood flow measurements based on Doppler ultrasound studies are the
      main clinical tool for studying the cardiovascular status of fetuses at risk for
      circulatory compromise. Usually, qualitative analysis of peripheral arteries and
      in particular clinical situations such as severe growth restriction or volume
      overload also of venous vessels close to the heart or of flow patterns in the
      heart is being used to gauge the level of compensation in a fetus. However,
      quantitative assessment of the driving force of the fetal circulation, the
      cardiac output remains an elusive goal in fetal medicine. This article reviews
      the methods for direct and indirect assessment of cardiac function and explains
      new clinical applications. Part 1 of this review describes the concept of cardiac
      function and cardiac output and the techniques that have been used to quantify
      output. Part 2 summarizes the use of arterial and venous Doppler studies in the
      fetus and gives a detailed description of indirect measurements of cardiac
      function (like indices derived from the duration of segments of the cardiac
      cycle) with current examples of their application.

PMID- 22161616
TI  - Fetal anterior wall thickness and amniotic fluid insulin levels: an
      interdependence?
AB  - PURPOSE: Excessive fetal fat as the hallmark of GDM pregnancy complications is
      one consequence of fetal hyperinsulinism. Noninvasive methods for fetal
      surveillance and measurement of fetal fat are needed. The purpose of this study
      was to test the hypothesis that measurements of the fetal anterior abdominal wall
      thickness (AAWT) in women with GDM will allow early detection of fetal
      hyperinsulinism. MATERIALS AND METHODS: Amniocentesis was performed between 28
      and 32 weeks of gestation (wks) in 220 women with GDM (diagnosed by 75 g oGTT at
      24 to 28 wks). Amniotic fluid insulin levels (AFIL) were determined by a
      commercially available radioimmunoassay. Transabdominal ultrasound provided fetal
      biometric measurements following standard procedures and the AAWT including fetal
      skin and subcutaneous tissue at the time of amniocentesis. Maternal parameters
      (weight, BMI, oGTT blood glucose levels and mean daily blood glucose levels) were
      correlated with fetal biometric data and with AFIL. RESULTS: There was no
      difference in AAWT in women with GDM and no correlation with mean AFIL. AFIL also
      did not correlate with any other fetal measurement or with mean oGTT blood
      glucose levels. AFIL only showed a correlation with maternal weight (p = 0.02)
      and maternal BMI (p = 0.01). The correlation was present for values both before
      pregnancy and at the time of amniocentesis. CONCLUSION: In the early third
      trimester, AAWT measurements do not correlate with fetal insulin levels.

PMID- 22161617
TI  - Fetal anemia of unknown cause--a diagnostic challenge.
AB  - PURPOSE: To assess the spectrum of underlying diseases in cases of fetal anemia
      in which the cause was unknown at the time of first and second transfusion or
      thereafter. MATERIALS AND METHODS: All patients who underwent intrauterine
      transfusion were identified in the perinatal databases of two tertiary referral
      centers for prenatal medicine and treatment between 2002 and June 2010. RESULTS:
      82 fetuses received intrauterine transfusion in the study period. A total of 356
      transfusions were performed in these patients. The causes of fetal anemia in our
      cohort were alloimmunization (32), parvovirus infection (23), feto-fetal
      transfusion syndrome (9), sacrococcygeal teratoma (2) and cytomegalovirus
      infection (1). In the remaining 15 cases, the cause of fetal anemia was unknown
      at the time of first and second transfusion, and could only be ascertained in the
      further course of pregnancy, in the postnatal period or was ultimately left in
      doubt. In all cases markedly elevated peak systolic velocities in the middle
      cerebral artery accurately predicted fetal anemia. The final diagnosis in these
      cases was fetomaternal hemorrhage (4), Blackfan-Diamond anemia (1), diffuse
      neonatal hemangiomatosis with chorangioma (1), kaposi-like hemangioendothelioma
      (1), elliptocytosis (1), neonatal hemochromatosis (1), mucopolysaccharidosis type
      VII (1) and in 5 cases the cause of fetal anemia remained unexplained. The latter
      5 cases had an uneventful postnatal course and did not require further
      transfusions in infancy. CONCLUSION: In cases of fetal anemia with negative
      indirect Coombs test and TORCH serology, rare causes of anemia have to be
      considered. Fetal studies should therefore include reticulocyte count, parameters
      of hemolysis, peripheral blood smear and fetal liver function tests. Maternal
      studies should involve a search for fetal red cells using flow cytometry rather
      than Kleihauer-Betke test.

PMID- 22161618
TI  - Atypical ductal hyperplasia of the breast diagnosed by ultrasonographically
      guided core needle biopsy.
AB  - PURPOSE: We analysed the ultrasonographic (US) features of atypical ductal
      hyperplasia (ADH) of the breast diagnosed by US-guided core needle biopsy (CNB)
      with the aim of identifying factors that affect the underestimation of ADH.
      MATERIALS AND METHODS: A total of 134 ADH lesions sampled by US-guided CNB were
      reviewed retrospectively. All lesions were evaluated for pattern, size, lesion
      characteristics and margins, and the corresponding surgical outcome or imaging
      follow-up was obtained. Each patient's clinical and radiological features were
      analysed to identify factors involved in ADH underestimation. RESULTS: The
      prevalence of malignancy in each pattern of lesions following surgical excision
      was 32/81 (40%) for solid masses, 14/31 (45%) for ductal patterns, 5/17 (29%) for
      complex cystic lesions and 2/5 (40%) for architectural distortions. Based on the
      results of surgical and US follow-up, none of the category 3 lesions was proven
      to be a malignancy. Malignancy was found in 17 (21%) of the 80 BI-RADS (Breast
      Imaging Reporting and Data System) category 4a lesions, 20 (74%) of the 27
      category 4b lesions, 12 (92%) of the 13 category 4c lesions, and four (100%) of
      the four category 5 lesions. Lesions with a higher US assessment category,
      lacking circumscribed margins, or a mammographic finding of suspected malignancy
      were all significantly associated with underestimation (p < 0.05 for each).
      CONCLUSION: US is useful in evaluating ADH lesions and in clarifying the
      indication for biopsy of these lesions. Familiarity with the frequency associated
      with malignancy for each feature will improve the utility of US in the work-up of
      these breast abnormalities.

PMID- 22161619
TI  - Fetal gastroschisis: a comparison of second vs. third-trimester bowel dilatation
      for predicting bowel atresia and neonatal outcomes.
AB  - PURPOSE: To compare various gestational ages and thresholds for diagnosing bowel
      dilatation in fetuses with gastroschisis and to evaluate the prognostic value of
      bowel dilatation for predicting postnatal bowel atresia and neonatal outcomes.
      MATERIALS AND METHODS: This was a retrospective observational study conducted
      from March 1997 to September 2009 that included 78 pregnancies with fetal
      gastroschisis. The predictive value of prenatal bowel dilatation for neonatal
      bowel atresia and postnatal complications was investigated in three subgroups:
      those with bowel dilatations >= 10 mm at a gestational age < 27 + 0 weeks, >= 10
      mm at a gestational age < 30 + 0 weeks and >= 18 mm at a gestational age >= 30
      weeks. RESULTS: Prenatally, 6 %, 81 % and 13 % of the bowel malformations were
      identified in the first, second and third trimesters, respectively. There were
      three stillbirths and three neonatal deaths, and the mean gestational age at
      delivery was 35.4 weeks (range 31 + 4 to 41 + 6). Bowel atresia was significantly
      correlated with prenatal bowel dilatation in all three subgroups. Bowel
      dilatations of >= 10 mm before 30 + 0 gestational weeks achieved the best
      performance in predicting bowel atresia, with a sensitivity of 89 % (8 / 9) and a
      specificity of 79 % (30 / 38). A prenatal bowel diameter >= 10 mm through 30
      completed weeks was also the best predictor of a prolonged neonatal hospital stay
      >= 8 weeks (sensitivity = 61.1, 11 / 18, p = 0.002). CONCLUSION: Fetuses with
      isolated gastroschisis successfully underwent postnatal surgery in most cases
      (93.2 %), except for one termination, one intrauterine death and 3 cases of
      neonatal death. A fetal bowel dilatation > 10 mm before 30 + 0 weeks had the
      highest predictive value for postnatal bowel complications.

PMID- 22161620
TI  - Diabetes and risk of esophageal and gastric adenocarcinomas.
AB  - Diabetes has been consistently associated with an increased risk of liver,
      pancreas and endometrial cancer and has been implicated as a risk factor for
      esophageal and gastric cancers, although this association has been less well
      studied. We sought to determine the role of diabetes in the etiology of
      esophageal, gastric cardia and distal gastric adenocarcinomas (DGAs). This
      analysis included patients with esophageal adenocarcinoma (EA) (n = 209), gastric
      cardia adenocarcinoma (GCA) (n = 257) and DGA (n = 382), and 1,309 control
      participants from a population-based case-control study conducted in Los Angeles
      County. The study included non-Hispanic whites, African Americans, Hispanics and
      Asian Americans. The association of diabetes with the three tumor types was
      estimated using polytomous logistic regression. Odds ratios (ORs) and
      corresponding 95% confidence intervals (CIs) were estimated. Nine percent of
      control participants and 13% of the case patients reported a history of diabetes.
      After adjustment for age, gender, race, birthplace, education, cigarette smoking
      status and body mass index, diabetes was associated with an increased risk of EA
      (OR, 1.48; 95% CI, 0.94-2.32; p = 0.089) and DGA (OR, 1.47; 95% CI, 1.01-2.15; p
      = 0.045), but was not associated with risk of GCA (OR, 0.96; 95% CI, 0.59-1.55; p
      = 0.87). However, the association between diabetes and risk of DGA was
      statistically significant only among patients for whom we interviewed their next
      of kin. Our study further investigated the association between diabetes and
      adenocarcinomas of the esophagus and distal stomach.

PMID- 22161623
TI  - Microvascular cricoid cartilage reconstruction with the thoracodorsal artery
      scapular tip autogenous transplant.
AB  - Conservation laryngeal surgery has been limited by difficulties with partial
      resection of the cricoid. Numerous options have been suggested that include
      temporoparietal flaps, free cartilage grafts, radial forearm free tissue
      transfers, and tracheal autotransplantation with vascular carriers. The authors
      present a one-stage procedure for the reconstruction of the cricoid cartilage
      based on the thoracodorsal artery scapular tip (Tdast) autogenous transplant that
      uses the curved tip of the scapula and does not create a secondary tracheal
      defect. Because the Tdast is a vascularized graft it may withstand radiation
      treatment.

PMID- 22161621
TI  - Quantitative redox biology: an approach to understand the role of reactive
      species in defining the cellular redox environment.
AB  - Systems biology is now recognized as a needed approach to understand the dynamics
      of inter- and intra-cellular processes. Redox processes are at the foundation of
      nearly all aspects of biology. Free radicals, related oxidants, and antioxidants
      are central to the basic functioning of cells and tissues. They set the cellular
      redox environment and, therefore, are the key to regulation of biochemical
      pathways and networks, thereby influencing organism health. To understand how
      short-lived, quasi-stable species, such as superoxide, hydrogen peroxide, and
      nitric oxide, connect to the metabolome, proteome, lipidome, and genome we need
      absolute quantitative information on all redox active compounds as well as
      thermodynamic and kinetic information on their reactions, i.e., knowledge of the
      complete redoxome. Central to the state of the redoxome are the interactive
      details of the superoxide/peroxide formation and removal systems. Quantitative
      information is essential to establish the dynamic mathematical models needed to
      reveal the temporal evolution of biochemical pathways and networks. This new
      field of Quantitative Redox Biology will allow researchers to identify new
      targets for intervention to advance our efforts to achieve optimal human health. 

PMID- 22161622
TI  - Routes for formation of S-nitrosothiols in blood.
AB  - S-nitrosothiols (RSNO) are involved in post-translational modifications of many
      proteins analogous to protein phosphorylation. In addition, RSNO have many
      physiological roles similar to nitric oxide ((*)NO), which are presumably
      involving the release of (*)NO from the RSNO. However, the much longer life span
      in biological systems for RSNO than (*)NO suggests a dominant role for RSNO in
      mediating (*)NO bioactivity. RSNO are detected in plasma in low nanomolar levels
      in healthy human subjects. These RSNO are believed to be redirecting the (*)NO to
      the vasculature. However, the mechanism for the formation of RSNO in vivo has not
      been established. We have reviewed the reactions of (*)NO with oxygen,
      metalloproteins, and free radicals that can lead to the formation of RSNO and
      have evaluated the potential for each mechanism to provide a source for RSNO in
      vivo. 

PMID- 22161624
TI  - Phylogenetic analysis of the light-harvesting system in Chromera velia.
AB  - Chromera velia is a newly discovered photosynthetic eukaryotic alga that has
      functional chloroplasts closely related to the apicoplast of apicomplexan
      parasites. Recently, the chloroplast in C. velia was shown to be derived from the
      red algal lineage. Light-harvesting protein complexes (LHC), which are a group of
      proteins involved in photon capture and energy transfer in photosynthesis, are
      important for photosynthesis efficiency, photo-adaptation/accumulation and photo
      protection. Although these proteins are encoded by genes located in the nucleus,
      LHC peptides migrate and function in the chloroplast, hence the LHC may have a
      different evolutionary history compared to chloroplast evolution. Here, we
      compare the phylogenetic relationship of the C. velia LHCs to LHCs from other
      photosynthetic organisms. Twenty-three LHC homologues retrieved from C. velia EST
      sequences were aligned according to their conserved regions. The C. velia LHCs
      are positioned in four separate groups on trees constructed by neighbour-joining,
      maximum likelihood and Bayesian methods. A major group of seventeen LHCs from C.
      velia formed a separate cluster that was closest to dinoflagellate LHC, and to
      LHC and fucoxanthin chlorophyll-binding proteins from diatoms. One C. velia LHC
      sequence grouped with LI1818/LI818-like proteins, which were recently identified
      as environmental stress-induced protein complexes. Only three LHC homologues from
      C. velia grouped with the LHCs from red algae.

PMID- 22161625
TI  - Therapeutic management of advanced adrenocortical carcinoma: what do we know in
      2011?
AB  - The prognosis of advanced adrenocortical carcinoma (ACC) is dismal but
      heterogeneous. In 2011, mitotane is the only drug approved in Europe and US for
      the treatment of advanced ACC. Mitotane exerts both antisecretory and
      antiproliferative effects, which are delayed over time, and requires careful
      biological and morphological evaluations coupled with mitotane plasma measurement
      monitoring. In the absence of demonstration of any superior activity of combined
      polychemotherapy, the least toxic regimen should be considered in routine care.
      Locoregional therapies, including surgery of the primary tumor and metastases,
      should be considered part of the therapeutic arsenal. A prolonged survival can be
      observed in the case of tumor objective response and/or high plasma mitotane
      levels. New protocols are urgently needed, coupled with ancillary studies
      dedicated to progress in the findings of predictors or surrogates. International
      networks and comprehensive databases gathering clinical and biological data
      constitute the prerequisites for progress.

PMID- 22161628
TI  - Identification of a 21 amino acid peptide conferring 3-hydroxypropionic acid
      stress-tolerance to Escherichia coli.
AB  - We report the identification of a novel small open reading frame in Escherichia
      coli. The sORF (called iroK) encodes a 21 amino cid peptide, which when
      translated confers a 133% (ca. 20 g/L) increase in resistance to 3
      hydroxypropionic acid. We show that iroK conferred tolerance is additive to
      previously identified tolerance mechanisms involving relief of inhibited
      metabolism, yet does not involve altered 3-HP transport. This result demonstrates
      the continued surprises that microbial genomes hold and emphasize the importance
      of comprehensive discovery methods in future strain and metabolic engineering
      efforts.

PMID- 22161627
TI  - Prospective self-gating for swallowing motion: a feasibility study in carotid
      artery wall MRI using three-dimensional variable-flip-angle turbo spin-echo.
AB  - Three-dimensional black-blood MRI is a promising noninvasive imaging technique
      for the assessment of atherosclerotic carotid artery disease. However, this
      technique is inherently susceptible to motion. In particular, swallowing can
      result in considerable wall motion at the carotid bifurcations, which may induce
      drastic image degradation or substantial overestimation of wall thickness. Self
      gating techniques have previously been shown to be capable of resolving and
      compensating for cardiac or respiratory motion during MRI. This work presents a
      self-gating-based prospective motion gating scheme that is combined with a three
      dimensional variable-flip-angle turbo spin-echo sequence (SPACE) for detecting
      swallowing motion. Self-gating signal readouts along the superior-inferior
      direction during each repetition time period are used to derive the projection
      profiles of the imaging volume. Based on cross-correlation analysis between the
      projection profiles and the corresponding reference profiles, swallowing motion
      can be detected and the motion-contaminated data will subsequently be discarded
      and reacquired in the next repetition time. The self-gated SPACE sequence was
      validated on eight healthy volunteers and two patients and, when compared with
      the conventional SPACE sequence, proved to be more resistant to swallowing motion
      and significantly improved image quality as well as the sharpness of carotid
      artery wall boundaries.

PMID- 22161629
TI  - Coordination sphere tuning of the electron transfer dissociation behavior of
      Cu(II)-peptide complexes.
AB  - In contrast to previous electron capture dissociation (ECD) studies, we find that
      electron transfer dissociation (ETD) of Cu(II)-peptide complexes can generate c-
      and z-type product ions when the peptide has a sufficient number of strongly
      coordinating residues. Double-resonance experiments, ion-molecule reactions, and
      collision-induced dissociation (CID) prove that the c and z product ions are
      formed via typical radical pathways without the associated reduction of Cu(II),
      despite the high second ionization energy of Cu. A positive correlation between
      the number of Cu(II) binding groups in the peptide sequence and the extent of c
      and z ion formation was also observed. This trend is rationalized by considering
      that the recombination energy of Cu(II) can be lowered by strong binding ligands
      to an extent that enables electron transfer to non-Cu sites (e.g., protonation
      sites) to compete with Cu(II) reduction, thereby generating c/z ions in a manner
      similar to that observed for protonated (i.e., nonmetalated) peptides.

PMID- 22161631
TI  - [Computer assistance to improve therapy planning for head neck oncology].
AB  - The ongoing development in therapies of head and neck malignomas has led to a
      further differentiation of treatment options. Complex surgical procedures, a wide
      variety of multi modal therapy options, changing radiation technologies (IMRT -
      Intensity-modulated radiation therapy) and numerous "targeted therapies"
      emphasize the need for a precise treatment plan. Beside this, imaging has seen
      significant improvements beyond the technical ones, e. g. with the implementation
      of PET/CT scanners. This increase in pre-therapeutic data volume, together with a
      diversification of treatment options calls for a further discussion of the basics
      of therapeutic decisions. Planning relevant data processing by computer assisted
      systems can aid in these decisions. This work describes the current status of
      relevant computer assisted systems undergoing first testing for head and neck
      cancer therapy planning. Here, the integration of 3-dimensional patient data
      plays a central role. This planning tool forms the integrated base for a further
      development in the areas of radiation planning, documentation and study
      management.

PMID- 22161633
TI  - [Post-hospitalization after care in accordance with paragraph 15 a SGB V. When
      does the responsibility of the hospital physician begin and when does it end? ].

PMID- 22161634
TI  - [Tracheotomy, tracheostomy].

PMID- 22161635
TI  - Sufficient dimension reduction for longitudinally measured predictors.
AB  - We propose a method to combine several predictors (markers) that are measured
      repeatedly over time into a composite marker score without assuming a model and
      only requiring a mild condition on the predictor distribution. Assuming that the
      first and second moments of the predictors can be decomposed into a time and a
      marker component via a Kronecker product structure that accommodates the
      longitudinal nature of the predictors, we develop first-moment sufficient
      dimension reduction techniques to replace the original markers with linear
      transformations that contain sufficient information for the regression of the
      predictors on the outcome. These linear combinations can then be combined into a
      score that has better predictive performance than a score built under a general
      model that ignores the longitudinal structure of the data. Our methods can be
      applied to either continuous or categorical outcome measures. In simulations, we
      focus on binary outcomes and show that our method outperforms existing
      alternatives by using the AUC, the area under the receiver-operator
      characteristics (ROC) curve, as a summary measure of the discriminatory ability
      of a single continuous diagnostic marker for binary disease outcomes.

PMID- 22161636
TI  - Comparison of optimized soft-tissue suppression schemes for ultrashort echo time
      MRI.
AB  - Ultrashort echo time (UTE) imaging with soft-tissue suppression reveals short
      T(2) components (typically hundreds of microseconds to milliseconds) ordinarily
      not captured or obscured by long-T(2) tissue signals on the order of tens of
      milliseconds or longer. Therefore, the technique enables visualization and
      quantification of short-T(2) proton signals such as those in highly collagenated
      connective tissues. This work compares the performance of the three most commonly
      used long-T(2) suppression UTE sequences, i.e., echo subtraction (dual-echo UTE),
      saturation via dual-band saturation pulses (dual-band UTE), and inversion by
      adiabatic inversion pulses (IR-UTE) at 3 T, via Bloch simulations and
      experimentally in vivo in the lower extremities of test subjects. For unbiased
      performance comparison, the acquisition parameters are optimized individually for
      each sequence to maximize short-T(2) signal-to-noise ratio (SNR) and contrast-to
      noise ratio (CNR) between short- and long-T(2) components. Results show excellent
      short-T(2) contrast which is achieved with these optimized sequences. A
      combination of dual-band UTE with dual-echo UTE provides good short-T(2) SNR and
      CNR with less sensitivity to B(1) homogeneity. IR-UTE has the lowest short-T(2)
      SNR efficiency but provides highly uniform short-T(2) contrast and is well suited
      for imaging short-T(2) species with relatively short T(1) such as bone water.

PMID- 22161638
TI  - Severe limited joint mobility syndrome in a child with type 1 diabetes mellitus.

PMID- 22161639
TI  - Successful engraftment and survival following allogeneic hematopoietic stem cell
      transplant in a child with familial hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic syndrome is a rare disorder mainly affecting children. Symptoms
      include prolonged fever, hepatosplenomegaly and cytopenias. Allogeneic stem cell
      transplant appears to provide the best overall cure rate in this disease. The
      authors report a young boy, the second child of consanguineous parents, diagnosed
      with familial hemophagocytic lymphohistiocytosis (HLH) who underwent allogeneic
      stem cell transplant form HLA matched father.

PMID- 22161640
TI  - Mef2c deletion in osteocytes results in increased bone mass.
AB  - Myocyte enhancer factors 2 (MEF2) are required for expression of the osteocyte
      bone formation inhibitor Sost in vitro, implying these transcription factors in
      bone biology. Here, we analyzed the in vivo function of Mef2c in osteocytes in
      male and female mice during skeletal growth and aging. Dmp1-Cre-induced Mef2c
      deficiency led to progressive decreases in Sost expression by 40% and 70% in
      femoral cortical bone at 3.5 months and 5 to 6 months of age. From 2 to 3 months
      onward, bone mass was increased in the appendicular and axial skeleton of Mef2c
      mutant relative to control mice. Cortical thickness and long bone and vertebral
      trabecular density were elevated. To assess whether the increased bone mass was
      related to the decreased Sost expression, we characterized 4-month-old
      heterozygous Sost-deficient mice. Sost heterozygotes displayed similar increases
      in long bone mass and density as Mef2c mutants, but the relative increases in
      axial skeletal parameters were mostly smaller. At the cellular level, bone
      formation parameters were normal in 3.5-month-old Mef2c mutant mice, whereas bone
      resorption parameters were significantly decreased. Correspondingly, cortical
      expression of the anti-osteoclastogenic factor and Wnt/beta-catenin target gene
      osteoprotegerin (OPG) was increased by 70% in Mef2c mutant males. Furthermore,
      cortical expression of the Wnt signaling modulators Sfrp2 and Sfrp3 was strongly
      deregulated in both sexes. In contrast, heterozygous Sost deficient males
      displayed mildly increased osteoblastic mineral apposition rate, but osteoclast
      surface and cortical expression of osteoclastogenic regulators including OPG were
      normal and Sfrp2 and Sfrp3 were not significantly changed. Together, our data
      demonstrate that Mef2c regulates cortical Sfrp2 and Sfrp3 expression and is
      required to maintain normal Sost expression in vivo. Yet, the increased bone mass
      phenotype of Mef2c mutants is not directly related to the reduced Sost
      expression. We identified a novel function for Mef2c in control of adult bone
      mass by regulation of osteoclastic bone resorption.

PMID- 22161641
TI  - Influence of solvent on the morphology and subsequent comminution of ibuprofen
      crystals by air jet milling.
AB  - Crystal morphology plays an important role in drug processing and delivery, which
      may be controlled during crystallisation. In this study, ibuprofen particles with
      different size and morphology were produced by controlled crystallisation in
      order to evaluate their impact on particle size reduction. Results suggest that
      the micronisation behaviour of ibuprofen was markedly influenced by the
      morphology and size of starting materials. It was possible to reduce the size of
      ibuprofen particles to sizes less than 5 um during dry milling, which is markedly
      below the reported brittle-ductile transition size. Results also indicate that
      the particle size reduction mechanism is influenced by the size and morphology of
      the starting ibuprofen crystals. Dissolution behaviour of ibuprofen was shown to
      be influenced by the solid surface chemistry of micronised drug particles. The
      molecular modelling study provided deeper understanding of the experimental
      findings observed in this study.

PMID- 22161642
TI  - NBS1 deficiency promotes genome instability by affecting DNA damage signaling
      pathway and impairing telomere integrity.
AB  - Studies revealed that Nijmegen Breakage Syndrome protein 1 (NBS1) plays an
      important role in maintaining genome stability, but the underlying mechanism is
      controversial and elusive. Our results using clinical samples showed that NBS1
      was involved in ataxia-telangiectasia mutated (ATM)-dependent pathway. NBS1
      deficiency severely affected the phosphorylation of ATM as well as its downstream
      targets. BrdU proliferation assay revealed a delay of NBS cells in inhibiting DNA
      synthesis after Doxorubicin (Dox) treatment. In addition, under higher
      concentrations of Dox, NBS cells exhibited a much lower level of apoptosis
      compared to their normal counterparts, indicating a resistance to Dox treatment.
      Accelerated telomere shortening was also observed in NBS fibroblasts, consistent
      with an early onset of cellular replicative senescence in vitro. This abnormality
      may be due to the shelterin protein telomeric binding factor 2 (TRF2) which was
      found to be upregulated in NBS fibroblasts. The dysregulation of telomere
      shortening rate and of TRF2 expression level leads to telomere fusions and
      cellular aneuploidy in NBS cells. Collectively, our results suggest a possible
      mechanism that NBS1 deficiency simultaneously affects ATM-dependent DNA damage
      signaling and TRF2-regulated telomere maintenance, which synergistically lead to
      genomic abnormalities.

PMID- 22161643
TI  - Rapamycin impairs UV induction of mutant-p53 overexpressing cell clusters without
      affecting tumor onset.
AB  - Because of its antitumor effect, the immunosuppressant rapamycin holds great
      promise for organ transplant recipients in that it may lower their cancer risk.
      In a mouse model, we showed previously that rapamycin inhibits the outgrowth of
      primary skin carcinomas induced by UV radiation. However, the tumors that did
      grow out showed an altered p53 mutation spectrum. Here, we investigated whether
      this shift in p53 mutations already occurred in the smallest tumors, which were
      not affected in onset. We found that rapamycin did not alter the mutational
      spectrum in small tumors and in preceding microscopic clusters of cells
      expressing mutant-p53. However, rapamycin did reduce the number of these cell
      clusters. As this reduction did not affect tumor onset, we subsequently
      investigated whether rapamycin merely suppressed expression of mutated p53. This
      was not the case, as we could demonstrate that switching from a diet with
      rapamycin to one without, or vice versa, did not affect the number of existing
      mutant-p53 expressing cell clusters. Hence, rapamycin actually reduced the
      formation of mutant-p53 cell clusters. In wild-type and p53-mutant mice, we could
      not measure a significant enhancement of UV-induced apoptosis, but we did observe
      clear enhancement in human skin equivalents. This was associated with a clear
      suppression of HIF1alpha accumulation. Thus, we conclude that rapamycin reduces
      the formation of mutant-p53-expressing cell clusters without affecting tumor
      onset, suggesting that tumors grow out of a minor subset of cell clusters, the
      formation of which is not affected by rapamycin.

PMID- 22161645
TI  - Diagnosis and gland-preserving minimally invasive therapy for Wharton's duct
      stenoses.
AB  - OBJECTIVES/HYPOTHESIS: The management of stenoses of Wharton's duct has so far
      been little investigated or systematized. The development of minimally invasive
      treatment methods, including sialendoscopy, has made preservation of gland
      function possible. STUDY DESIGN: Retrospective study in a tertiary referral
      center. METHODS: A total of 153 stenoses of the submandibular duct were diagnosed
      and treated in 138 patients. Ultrasound and sialendoscopy were the first-choice
      diagnostic measures. A total of 62.7% of the stenoses were located in the distal,
      11.1% in the middle segment, and 18.3% in the proximal to posthilar duct. Diffuse
      stenoses were observed in 7.8% of the cases. Sialendoscopy-assisted intraductal
      cortisone administration, interventional sialendoscopy, and transoral ductal
      surgery were the treatment options. The mean period between treatment and data
      collection was 52.5 months. RESULTS: Fibrotic stenoses were diagnosed in 88.3%
      and bilateral involvement in 8.6% of the cases. Distal stenoses were treated
      predominantly by ductal incision (79.2%). Stenoses of the midsubmandibular duct
      were treated conservatively in 29.4% or with sialendoscopy or ductal incision in
      35.3% of cases each. Proximal up to posthilar stenoses could be dilated by
      interventional sialendoscopy in 82.2%. In 25% of all diffuse stenoses, glandular
      resection was carried out, representing 2.6% of all stenoses. Glandular function
      was preserved in 97.8% of cases. CONCLUSIONS: Stenoses of the submandibular duct
      can be treated using minimally invasive procedures and with preservation of
      glandular function with a high success rate. Ductal incision procedures are the
      most important measure, but sialendoscopy becomes more important the more
      centrally the stenosis is located.

PMID- 22161644
TI  - Unravelling the pluripotency paradox in fetal and placental mesenchymal stem
      cells: Oct-4 expression and the case of The Emperor's New Clothes.
AB  - Mesenchymal stem cells (MSC) from fetal-placental tissues have translational
      advantages over their adult counterparts, and have variably been reported to
      express pluripotency markers. OCT-4 expression in fetal-placental MSC has been
      documented in some studies, paradoxically without tumourogenicity in vivo. It is
      possible that OCT-4 expression is insufficient to induce true "stemness", but
      this issue is important for the translational safety of fetal-derived MSC. To
      clarify this, we undertook a systematic literature review on OCT-4 in fetal or
      adnexal MSC to show that most studies report OCT-4 message or protein expression,
      but no study provides definitive evidence of true OCT-4A expression. Discrepant
      findings were attributable not to different culture conditions, tissue sources,
      or gestational ages but instead to techniques used. In assessing OCT-4 as a
      pluripotency marker, we highlight the challenges in detecting the correct OCT-4
      isoform (OCT-4A) associated with pluripotency. Although specific detection of OCT
      4A mRNA is achievable, it appears unlikely that any antibody can reliably
      distinguish between OCT-4A and the pseudogene OCT-4B. Finally, using five robust
      techniques we demonstrate that fetal derived-MSC do not express OCT-4A (or by
      default OCT-4B). Reports suggesting OCT-4 expression in fetal-derived MSC warrant
      reassessment, paying attention to gene and protein isoforms, pseudogenes, and
      antibody choice as well as primer design. Critical examination of the OCT-4
      literature leads us to suggest that OCT-4 expression in fetal MSC may be a case
      of "The Emperor's New Clothes" with early reports of (false) positive expression
      amplified in subsequent studies without critical attention to emerging
      refinements in knowledge and methodology.

PMID- 22161646
TI  - [Formation of centers in general and abdominal surgery -- necessity or trend?].
AB  - The introduction of the DRG (diagnosis-related groups) system as basis for
      reimbursement in the German health-care system has led to a mentality of quality
      orientation and verification of therapeutic results. An immediate result was the
      formation of medical "centres" on rather different levels and consequently the
      inauguration of institutions, authorities, and organisations to review these
      centres. Finally, a range of certifications was installed in order to stratify
      the rather diverse aims of different centres. This review critically evaluates
      the current situation in the field of general and abdominal surgery in Germany.

PMID- 22161647
TI  - [Small intestinal signet-ring cell carcinoma in Crohn's disease: case report and
      review of the literature].

PMID- 22161648
TI  - [A rare cause of painless jaundice in a 38-year-old patient].

PMID- 22161649
TI  - Changes in lower extremity muscle mass and muscle strength after weight loss in
      obese patients with knee osteoarthritis: a prospective cohort study.
AB  - OBJECTIVE: To investigate the effects of low-energy diet-induced weight loss on
      lower-extremity muscle mass and knee muscle strength in obese patients with knee
      osteoarthritis (OA), and the associations of these effects. METHODS: We studied
      159 obese patients with knee OA and available data from body composition analysis
      that had been performed using dual x-ray absorptiometry scanning and isometric
      muscle strength testing of the knee in extension and in flexion. The data had
      been obtained as part of a randomized controlled trial, with measurements
      performed before and after a supervised low-energy diet-induced weight loss
      intervention lasting 16 weeks. RESULTS: The patients lost an average of 12.9 kg
      (95% confidence interval [95% CI] 10.2, 15.7) (13% of baseline weight). The
      weight loss consisted of 10.9 kg fat mass (95% CI 8.9, 12.9), of which 3.8 kg
      (95% CI 2.7, 4.9) was leg fat mass. Total lean body mass was reduced by 1.9 kg
      (95% CI 0.05, 3.8), of which 0.785 kg (95% CI 0.09, 1.476) was leg lean mass.
      Absolute muscle strength decreased by ~3-4% after the weight loss, whereas body
      mass-normalized muscle strength increased by 11-12%. At baseline, leg lean mass
      was significantly related to muscle strength, but changes in these measurements
      at followup were not related. CONCLUSION: Weight loss induced by a low-energy
      diet led to independent losses of leg muscle tissue and strength. The weight loss
      was accompanied by increased normalized muscle strength along with improved self
      reported disability and pain--all of which are beneficial to patients with knee
      OA. The present results suggest that significant weight loss in patients with
      knee OA should be followed by an exercise regimen to restore or increase muscle
      mass.

PMID- 22161650
TI  - Four-dimensional flow MRI using spiral acquisition.
AB  - Time-resolved three-dimensional phase-contrast MRI is an important tool for
      physiological as well as clinical studies of blood flow in the heart and vessels.
      The application of the technique is, however, limited by the long scan times
      required. In this work, we investigate the feasibility of using spiral readouts
      to reduce the scan time of four-dimensional flow MRI without sacrificing quality.
      Three spiral approaches are presented and evaluated in vivo and in vitro against
      a conventional Cartesian acquisition. In vivo, the performance of each method was
      assessed in the thoracic aorta in 10 volunteers using pathline-based analysis and
      cardiac output analysis. Signal-to-noise ratio and background phase errors were
      investigated in vitro. Using spiral readouts, the scan times of a four
      dimensional flow acquisition of the thoracic aorta could be reduced 2-3-fold,
      with no statistically significant difference in pathline validity or cardiac
      output. The shortened scan time improves the applicability of four-dimensional
      flow MRI, which may allow the technique to become a part of a clinical workflow
      for cardiovascular functional imaging.

PMID- 22161651
TI  - 384 hanging drop arrays give excellent Z-factors and allow versatile formation of
      co-culture spheroids.
AB  - We previously reported the development of a simple, user-friendly, and versatile
      384 hanging drop array plate for 3D spheroid culture and the importance of
      utilizing 3D cellular models in anti-cancer drug sensitivity testing. The 384
      hanging drop array plate allows for high-throughput capabilities and offers
      significant improvements over existing 3D spheroid culture methods. To allow for
      practical 3D cell-based high-throughput screening and enable broader use of the
      plate, we characterize the robustness of the 384 hanging drop array plate in
      terms of assay performance and demonstrate the versatility of the plate. We find
      that the 384 hanging drop array plate performance is robust in fluorescence- and
      colorimetric-based assays through Z-factor calculations. Finally, we demonstrate
      different plate capabilities and applications, including: spheroid transfer and
      retrieval for Janus spheroid formation, sequential addition of cells for
      concentric layer patterning of different cell types, and culture of a wide
      variety of cell types.

PMID- 22161682
TI  - CD8+ T cells patrol HSV-1-infected trigeminal ganglia and prevent viral
      reactivation.
AB  - A hallmark of herpes viruses is their capacity to cause recurrent disease.
      Recurrences of herpes simplex virus (HSV)-1 disease do not result from
      reinfection from external sources, but rather from reactivation of virus that is
      maintained in a latent state in sensory neurons and periodically reactivates from
      latency to cause recurrent disease. Recent findings implicate HSV-specific CD8(+)
      T cells in immune surveillance of HSV-1 latently infected sensory neurons in
      trigeminal ganglia (TG) and inhibition of HSV-1 reactivation from latency. This
      review summarizes recent findings regarding the characteristics of the TG
      resident CD8(+) T cell population and certain unique obstacles that might
      complicate the development of therapeutic vaccines.

PMID- 22161683
TI  - Investigation of varicella-zoster virus neurotropism and neurovirulence using
      SCID mouse-human DRG xenografts.
AB  - Varicella-zoster virus (VZV) is a medically important human alphaherpesvirus.
      Investigating pathogenic mechanisms that contribute to VZV neurovirulence are
      made difficult by a marked host restriction. Our approach to investigating VZV
      neurotropism and neurovirulence has been to develop a mouse-human xenograft model
      in which human dorsal root ganglia (DRG) are maintained in severe compromised
      immunodeficient (SCID) mice. In this review, we will describe our key findings
      using this model in which we have demonstrated that VZV infection of SCID DRG
      xenograft results in rapid and efficient spread, enabled by satellite cell
      infection and polykaryon formation, which facilitates robust viral replication
      and release of infectious virus. In neurons that persist following this acute
      replicative phase, VZV genomes are present at low frequency with limited gene
      transcription and no protein synthesis, a state that resembles VZV latency in the
      natural human host. VZV glycoprotein I and interaction between glycoprotein I and
      glycoprotein E are critical for neurovirulence. Our work demonstrates that the
      DRG model can reveal characteristics about VZV replication and long-term
      persistence of latent VZV genomes in human neuronal tissues, in vivo, in an
      experimental system that may contribute to our knowledge of VZV
      neuropathogenesis.

PMID- 22161686
TI  - Changes in 3-dimensional bone structure indices in hypoparathyroid patients
      treated with PTH(1-84): a randomized controlled study.
AB  - Hypoparathyroidism (hypoPT) is characterized by a state of low bone turnover and
      high bone mineral density (BMD) despite conventional treatment with calcium
      supplements and active vitamin D analogues. To assess effects of PTH substitution
      therapy on 3-dimensional bone structure, we randomized 62 patients with hypoPT
      into 24 weeks of treatment with either PTH(1-84) 100 ug/day subcutaneously or
      similar placebo as an add-on therapy. Micro-computed tomography was performed on
      44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24 weeks of
      treatment. Compared with placebo, PTH caused a 27% lower trabecular thickness (p
      < 0.01) and 4% lower trabecular bone tissue density (p < 0.01), whereas
      connectivity density was 34% higher (p < 0.05). Trabecular tunneling was evident
      in 11 (48%) of the biopsies from the PTH group. Patients with tunneling had
      significantly higher levels of biochemical markers of bone resorption and
      formation. At cortical bone, number of Haversian canals per area was 139% higher
      (p = 0.01) in the PTH group, causing a tendency toward an increased cortical
      porosity (p = 0.09). At different subregions of the hip, areal BMD (aBMD) and
      volumetric BMD (vBMD), as assessed by dual-energy X-ray absorptiometry (DXA) and
      quantitative computed tomography (QCT), decreased significantly by 1% to 4% in
      the PTH group. However, at the lumbar spine, aBMD decreased by 1.8% (p < 0.05),
      whereas vBMD increased by 12.8% (p = 0.02) in the PTH compared with the placebo
      group.

PMID- 22161684
TI  - Lack of reelin modifies the gene expression in the small intestine of mice.
AB  - We recently demonstrated that the mucosa of the small intestine of the rat
      expresses reelin and some components of its signaling system. The current study
      evaluates whether reelin affects the intestinal gene expression profile using
      microarray analysis and reeler mice, a natural mutant in which reelin is not
      expressed. The effect of the mutation on body weight and intestinal morphology is
      also evaluated. The mutation reduces body and intestinal weight during the first
      2 months of age and modifies the morphology of the crypts and villi. For the
      microarray assays, total RNA was obtained from either isolated epithelial cells
      or intact small intestine. Of the 45,101 genes present in the microarray the
      mutation significantly alters the expression of 62 genes in the isolated
      epithelial cell samples and of 84 in the intact small intestine. The expression
      of 83% of the genes tested for validation was substantiated by reverse
      transcriptase polymerase chain reaction. The mutation notably up-regulates genes
      involved in intestinal metabolism, while it down-regulates genes related with
      immune response, inflammation, and tumor development. Genes involved in cell
      proliferation, differentiation, apoptosis, membrane transport and cytoskeleton
      are also differently expressed in the reeler mice as compared with the control.
      This is the first report showing that the lack of reelin modifies intestinal
      morphology and gene expression profile and suggests a role for reelin in
      intestinal epithelium homeostasis.

PMID- 22161687
TI  - Program impact evaluation using a matching method with panel data.
AB  - Difference-in-differences with matching is a popular method to measure the impact
      of an intervention in health and social sciences. This method requires baseline
      data, that is, data before interventions, which are not always available in
      reality. Instead, panel data with two time periods are often collected after
      interventions begin. In this paper, a simple matching method is proposed to
      measure the impact of an intervention using two-period panel data after the
      intervention. The method is illustrated by the measurement of the effect of
      health insurance in Vietnam using household panel data.

PMID- 22161688
TI  - Vial freeze-drying, part 1: new insights into heat transfer characteristics of
      tubing and molded vials.
AB  - In order to optimize a freeze-drying cycle, information regarding the heat
      transfer characteristics of the container system is imperative. Two most recently
      developed tubing (TopLyoTM) and molded (EasyLyoTM) vial designs were compared
      with a standard serum tubing and molded vial, a polymer vial (TopPacTM), and an
      amber molded EasyLyoTM. In addition, the impact of methodology on the
      determination of reliable vial heat transfer coefficient (K(v) ) data is examined
      in detail. All K(v) s were gravimetrically determined by sublimation tests with
      pure water at 50, 100, 200, and 400 mTorr. In contrast to the traditional
      assumption that molded vials exhibit inefficient heat transfer characteristics,
      these vials showed a very similar performance compared with their serum tubing
      counterparts in the relevant pressure range for freeze-drying. At 100 mTorr, the
      TopLyoTM center vials show only 4% higher K(v) values than the EasyLyoTM center
      vials. All glass vials outmatch the polymer vial in terms of heat transfer, up to
      30% elevated heat transfer for the TopLyoTM center vials at 400 mTorr.
      Sublimation tests have demonstrated to be a valuable tool to investigate the heat
      transfer characteristics of vials, but results are dependent on methodology. New
      developments in molded vial manufacturing lead to improved heat transfer
      performance.

PMID- 22161689
TI  - Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated
      by the absence or presence of the ephrin-B2 ligand.
AB  - Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial
      cancers and linked to tumor progression by promoting angiogenesis, increasing
      survival and facilitating invasion and migration. However, other studies have
      reported loss of EphB4 suggesting a tumor suppressor function in some cancers.
      These opposing roles may be regulated by (i) the presence of the primary ligand
      ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the
      absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways
      that contribute to tumor promotion. To explore this theory, EphB4 was
      overexpressed in the prostate cancer cell line 22Rv1 and the mammary epithelial
      cell line MCF-10A. Overexpressed EphB4 localized to lipid-rich regions of the
      plasma membrane and confirmed to be ligand-responsive as demonstrated by
      increased phosphorylation of ERK1/2 and internalization. EphB4 overexpressing
      cells demonstrated enhanced anchorage-independent growth, migration and invasion,
      all characteristics associated with an aggressive phenotype, and therefore
      supporting the hypothesis that overexpressed EphB4 facilitates tumor promotion.
      Importantly, these effects were reversed in the presence of ephrin-B2 which led
      to a reduction in EphB4 protein levels, demonstrating that ligand-dependent
      signaling is tumor suppressive. Furthermore, extended ligand stimulation caused a
      significant decrease in proliferation that correlated with a rise in caspase-3/7
      and -8 activities. Together, these results demonstrate that overexpression of
      EphB4 confers a transformed phenotype in the case of MCF-10A cells and an
      increased metastatic phenotype in the case of 22Rv1 cancer cells and that both
      phenotypes can be restrained by stimulation with ephrin-B2, in part by reducing
      EphB4 levels.

PMID- 22161690
TI  - Nonuniform and multidimensional Shinnar-Le Roux RF pulse design method.
AB  - The Shinnar-Le Roux (SLR) radiofrequency (RF) pulse design algorithm is widely
      used for designing slice-selective RF pulses due to its intuitiveness,
      optimality, and speed. SLR is limited, however, in that it is only capable of
      designing one-dimensional pulses played along constant gradients. We present a
      nonuniform SLR RF pulse design framework that extends most of the capabilities of
      classical SLR to nonuniform gradient trajectories and multiple dimensions.
      Specifically, like classical SLR, the new method is a hard pulse approximation
      based technique that uses filter design relationships to produce the lowest power
      RF pulse that satisfies target magnetization ripple levels. The new method is
      validated and compared with methods conventionally used for nonuniform and
      multidimensional large-tip-angle RF pulse design.

PMID- 22161691
TI  - [Editorial].

PMID- 22161692
TI  - [Anatomy of knee arthritis--consequences for the planning of TKAs].

PMID- 22161693
TI  - [Fractures of the radial head and neck].
AB  - Fractures of the radial head and neck are the most common involving the elbow and
      account for 5 % of all fractures in adult individuals. Due to the complex anatomy
      and biomechanics of the elbow joint radial head fractures are challenging,
      particularly the comminuted ones. Detailed knowledge of the complex joint
      anatomy, biomechanics and operative approaches are indispensable for analysing
      and building a treatment plan. The aim of radial head fracture treatment is to
      restore the anatomy and joint kinematics, achieve a stable and pain-free range-of
      motion and to avoid posttraumatic degenerative changes. Treatment depends on the
      type of fracture and accompanying injuries. It ranges from conservative treatment
      with early initiation of physical therapy to open reduction and internal
      fixation. Sophisticated reconstructive efforts with combined screw- and plate
      osteosynthesis, partial resection or radial head arthroplasty are needed in
      comminuted fractures. The purpose of this article is to give a detailed review of
      the anatomy, biomechanics and fracture mechanism. Clinical examination techniques
      are displayed and operative approaches as well as the conservative and operative
      treatment algorithms are illustrated.

PMID- 22161694
TI  - Effects of donepezil on cognitive performance after sleep deprivation.
AB  - OBJECTIVES: To identify tasks that were sensitive to a temporary decline in
      cognitive performance after sleep deprivation and to investigate the ability of
      the acetylcholinesterase inhibitor donepezil to reverse any sleep deprivation
      induced impairment. METHODS: Thirty healthy volunteers were administered either a
      5-mg daily dose of donepezil or placebo for 14-17 days, in a double-blind
      parallel group design, then underwent either 24 h sleep deprivation or a normal
      night of sleep in non-blinded crossover, and were subsequently tested on a
      battery of cognitive tasks designed to measure different components of memory and
      executive function. RESULTS: Sleep deprivation selectively impaired performance
      on several memory tasks whilst also impairing non-memory function on these tasks.
      Performance on other tasks was spared. Despite partially reversing the decline in
      subjective alertness associated with sleep deprivation, treatment with donepezil
      failed to significantly reverse the decline in cognitive performance on any of
      the tasks. CONCLUSIONS: The results demonstrate the sensitivity of certain tests,
      particularly those that measure memory function, to cognitive impairment after
      sleep deprivation. The inability of donepezil to reverse this performance decline
      suggests that the sleep deprivation model of cognitive impairment may not be
      suitable for detecting pro-cognitive effects of cholinergic augmentation.

PMID- 22161695
TI  - Influence of dense-array EEG cap on fMRI signal.
AB  - Dense-array (>64 channel) electroencephalography (EEG) systems are increasingly
      being used in simultaneous EEG-functional magnetic resonance imaging (fMRI)
      studies. However, with increasing channel count, dense-array EEG caps can induce
      more severe signal dropout in the MRI images than conventional systems due to the
      radiofrequency shielding effect of the denser wire bundle. This study
      investigates the influence of a 256-channel EEG cap on MRI image quality and
      detection sensitivity of blood oxygen level dependent fMRI signal. A theoretical
      model is first established to describe the impact of the EEG cap on anatomic
      signal, noise, signal-to-noise ratio, and contrast-to-noise ratio of blood oxygen
      level dependent signal. Seven subjects were scanned to measure and compare the
      T(2)-weighted image quality and fMRI detection sensitivity with and without the
      EEG cap using an auditory/visual/sensorimotor task. The results show that the
      dense-array EEG cap can substantially reduce the anatomic signal in the brain
      areas (visual cortex) near the conducting wires (average percent decrease ~ 38%).
      However, the image signal-to-noise ratio with and without the EEG cap was
      comparable (percent decrease < 8%, not statistically significant), and there was
      no statistically significant difference in the extent of blood oxygen level
      dependent activation. This suggests that the ability to detect fMRI signal is
      nearly unaffected by dense-array EEG caps in simultaneous EEG-fMRI experiments.

PMID- 22161697
TI  - Brief report: genotype, phenotype, and clinical course in five patients with PAPA
      syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne).
AB  - OBJECTIVE: To describe the genotypes, phenotypes, immunophenotypes, and
      treatments of PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum,
      and acne), a rare autoinflammatory disease, in 5 patients. METHODS: Clinical
      information was gathered from medical records and through interviews with 5
      patients from 4 kindreds. PSTPIP1 (CD2BP1) exon 10 and exon 11 sequencing was
      performed in each patient. Neutrophil granule content and cytokine levels were
      determined in plasma and stimulated peripheral blood mononuclear cells (PBMCs)
      from patients and controls. RESULTS: We identified 2 previously described PAPA
      syndrome-associated PSTPIP1 mutations, A230T and E250Q, and a novel change,
      E250K. Disease penetrance was incomplete, with variable expressivity. The
      cutaneous manifestations included pathergy, cystic acne, and pyoderma
      gangrenosum. Interleukin-1beta (IL-1beta) and circulating neutrophil granule
      enzyme levels were markedly elevated in patients compared to those in controls.
      PBMC stimulation studies demonstrated impaired production of IL-10 and enhanced
      production of granulocyte-macrophage colony-stimulating factor. Good resolution
      of pyoderma gangrenosum was achieved in 3 patients with tumor necrosis factor
      alpha (TNFalpha) blockade treatment. CONCLUSION: This analysis of 5 patients
      demonstrates that mutations in PSTPIP1 are incompletely penetrant and variably
      expressed in the PAPA syndrome. Neutrophil granule proteins are markedly elevated
      ex vivo and in the plasma, and elevated levels might be compatible with a
      diagnosis of PAPA syndrome. TNFalpha blockade appears to be effective in treating
      the cutaneous manifestations of PAPA syndrome.

PMID- 22161723
TI  - Possible involvement of Wnt11 in colorectal cancer progression.
AB  - Our previous report revealed that the expression of Frizzled-7 (FZD7) in
      colorectal cancer (CRC) and its possible role in CRC progression. In this study
      we measured the expression levels of candidate FZD7 ligands, Wnt3 and Wnt11 in
      colon cancer cell lines (n = 7) and primary CRC tissues (n = 133) by quantitative
      RT-PCR. We also examined the functional effects of Wnt11 with the use of Wnt11
      transfectants of colon cancer HCT-116 cells. Wnt11 transfectants showed the
      increased proliferation and migration/invasion activities compared to mock cells.
      Western blot analysis of transfectants revealed that phosphorylation of JNK and c
      jun was increased after Wnt11 transfection. Wnt11 mRNA expression was
      significantly higher in the stage I, II, III, or IV tumor tissues than in non
      tumor tissues (overall P < 0.003), while there was no significant difference in
      Wnt3 mRNA expression between tumor and non-tumor tissues. In addition, Wnt11 mRNA
      expression was significantly higher in patients with recurrence or death after
      surgery than in those with no recurrence (disease free) after surgery (P =
      0.018). We also compared the expression levels of Wnt11 mRNA with those of FZD7
      mRNA in the same CRC samples. Wnt11 mRNA expression was significantly higher in
      patients with higher FZD7 mRNA levels than in those with lower FZD7 mRNA levels
      (P = 0.0005). The expression levels of Wnt11 mRNA were correlated with those of
      FZD7 mRNA (P < 0.0001). These data suggest that Wnt11 may play an important role
      in CRC progression.

PMID- 22161696
TI  - The therapeutic potential of epigenetics in autoimmune diseases.
AB  - Autoimmune diseases now include over 100 conditions and are estimated to affect
      over 20 million people in the United States or 5% of the world population with
      numerous geographical differences coined as geoepidemiology. Further, concordance
      rates in monozygotic twins are significantly higher compared to dizygotic sets
      while being significantly below 50% for most autoimmune diseases. These lines of
      evidence suggest that additional mechanisms are needed to link the individual
      susceptibility with the proposed chemical and infectious factors in the
      environment. Epigenetics may well constitute this missing link to include DNA
      methylation, histone changes, and microRNA which contribute to the epigenome
      characterizing specific diseases. Importantly, these epigenetic changes may be
      ideal targets for new personalized treatments as suggested by data in cancer. A
      number of chemical and physical factors, along with proposed infectious agents or
      aging, are involved in the etiopathogenesis of autoimmune diseases through
      epigenetic changes. The most prominent evidence on the association between
      environment and autoimmunity has been reported in systemic lupus erythematosus,
      but similar mechanisms were proposed in rheumatoid arthritis, systemic sclerosis,
      and type 1 diabetes.

PMID- 22161724
TI  - Functional taping applied to upper limb of children with hemiplegic cerebral
      palsy: a pilot study.
AB  - Functional taping with elastic bandages and adhesive tapes could limit the action
      of upper limb spastic muscles and sustain that of weaker muscles in children with
      hemiplegic cerebral palsy (CP). 16 young children with CP (3+/-2 years old) were
      enrolled in this pilot study including 5 months of taping in conjunction with
      conventional physical therapy, followed by 7 months of physical therapy alone
      (taping wash-out), and other 5 months of taping plus therapy. Large improvements
      in the Melbourne assessment score were found in the first period in which taping
      was used (+15.4%, p<0.001) and also in the second one despite 8 drop-outs (+8.4%,
      p=0.012), but not during the taping wash-out (- 4.6%; p=0.093). These results
      suggest that children with CP could benefit from the continuous correction
      provided by taping in order to limit the development of improper upper limb motor
      schemas and to favour that of proper ones.

PMID- 22161725
TI  - Health-related quality of life of mothers of very low birth weight children at
      the age of five: results from the Newborn Lung Project Statewide Cohort Study.
AB  - PURPOSE: This study aimed to determine the health-related quality of life (HRQoL)
      in mothers of 5-year-old very low birth weight (VLBW) and normal birth weight
      (NBW) children, with a focus on the role of stress. METHODS: This cohort study is
      ancillary to the Newborn Lung Project. A telephone interview collected
      information on symptoms of stress and HRQoL from 297 mothers of VLBW children and
      290 mothers of NBW children who were enrolled in the Newborn Lung Project
      Statewide Cohort Study. Staged multiple regression analyses were used to evaluate
      the relationship between caregiver status and maternal HRQoL and the role stress
      played in this relationship. Additional multiple regression analyses were also
      used to evaluate the correlates of poor maternal HRQoL among VLBW mothers.
      RESULTS: Mothers of VLBW children experienced worse physical and mental HRQoL
      than mothers of NBW children. Adjusted analyses showed that physical HRQoL was
      significantly different between these mothers (beta: -1.87, P = 0.001); this
      relationship was attenuated by maternal stress. Among the mothers of VLBW
      children, stress significantly contributed to adverse HRQoL outcomes when
      children were aged five. Child behavior problems at the age of two were also
      associated with worse subsequent maternal mental HRQoL (beta: -0.18, P = 0.004),
      while each week of neonatal intensive care unit stay was associated with worse
      physical HRQoL (beta: -0.26, P = 0.02). CONCLUSIONS: Caring for a VLBW child is
      negatively associated with the HRQoL of mothers; this relationship might be, in
      part, explained by maternal stress. Addressing maternal stress may be an
      important way to improve long-term HRQoL.

PMID- 22161726
TI  - The effect of weight loss on changes in health-related quality of life among
      overweight and obese women with urinary incontinence.
AB  - OBJECTIVE: To estimate the effect of change in weight and change in urinary
      incontinence (UI) frequency on changes in preference-based measures of health
      related quality of life (HRQL) among overweight and obese women with UI
      participating in a weight loss trial. METHODS: We conducted a longitudinal cohort
      analysis of 338 overweight and obese women with UI enrolled in a randomized
      clinical trial comparing a behavioral weight loss intervention to an educational
      control condition. At baseline, 6, and 18 months, health utilities were estimated
      using the Health Utilities Index Mark 3 (HUI3), a transformation of the SF-36 to
      the preference-based SF-6D, and the estimated Quality of Well-Being (eQWB) score
      (a summary calculated from the SF-36 physical functioning, mental health, bodily
      pain, general health perceptions, and role limitations-physical subscale scores).
      Potential predictors of changes in these outcomes were examined using generalized
      estimating equations. RESULTS: In adjusted multivariable models, weight loss was
      associated with improvement in HUI3, SF-6D, and eQWB at 6 and 18 months (P <
      0.05). Increases in physical activity also were independently associated with
      improvement in HUI3 (P = 0.01) and SF-6D (P = 0.006) scores at 18 months. In
      contrast, reduction in UI frequency did not predict improvements in HRQL at 6 or
      18 months. CONCLUSION: Weight loss and increased physical activity, but not
      reduction in UI frequency, were strongly associated with improvements in health
      utilities measured by the HUI3, SF-6D, and eQWB. These findings provide important
      information that can be used to inform cost-utility analyses of weight loss
      interventions.

PMID- 22161727
TI  - Aerobic epoxidation of olefins catalyzed by the cobalt-based metal-organic
      framework STA-12(Co).
AB  - A Co-based metal-organic framework (MOF) was investigated as a catalytic material
      in the aerobic epoxidation of olefins in DMF and exhibited, based on catalyst
      mass, a remarkably high catalytic activity compared with the Co-doped zeolite
      catalysts that are typically used in this reaction. The structure of STA-12(Co)
      is similar to that of STA-12(Ni), as shown by XRD Rietveld refinement and is
      stable up to 270  degrees C. For the epoxidation reaction, significantly
      different selectivities were obtained depending on the substrate. Although
      styrene was epoxidized with low selectivity due to oligomerization, (E)-stilbene
      was converted with high selectivities between 80 and 90 %. Leaching of Co was low
      and the reaction was found to proceed mainly heterogeneously. The catalyst was
      reusable with only a small loss of activity. The catalytic epoxidation of
      stilbene with the MOF featured an induction period, which was, interestingly,
      considerably reduced by styrene/stilbene co-epoxidation. This could be traced
      back to the formation of benzaldehyde promoting the reaction. Detailed parameter
      and catalytic studies, including in situ EPR and EXAFS spectroscopy, were
      performed to obtain an initial insight into the reaction mechanism.

PMID- 22161729
TI  - Co-culture of stromal and erythroleukemia cells in a perfused hollow fiber
      bioreactor system as an in vitro bone marrow model for myeloid leukemia.
AB  - We have developed a hematopoietic co-culture system using the hollow fiber
      bioreactor (HFBR) as a potential in vitro bone marrow model for evaluating
      leukemia. Supporting stroma using HS-5 cells was established in HFBR system and
      the current bioprocess configuration yielded an average glucose consumption of
      640 mg/day and an average protein concentration of 6.40 mg/mL in the
      extracapillary space over 28 days. Co-culture with erythroleukemia K562 cells was
      used as a model for myelo-leukemic cell proliferation and differentiation. Two
      distinct localizations of K562 cells (loosely adhered and adherent cells) were
      identified and characterized after 2 weeks. The HFBR co-culture resulted in
      greater leukemic cell expansion (3,130 fold vs. 43 fold) compared to a standard
      tissue culture polystyrene (TCP) culture. Majority of expanded cells (68%) in
      HFBR culture were the adherent population, highlighting the importance of cell
      cell contact for myelo-leukemic proliferation. Differentiation tendencies in TCP
      favored maturation toward monocyte and erythrocyte lineages but maintained a pool
      of myeloid progenitors. In contrast, HFBR co-culture exhibited greater lineage
      diversity, stimulating monocytic and megakaryocytic differentiation while
      inhibiting erythroid maturation. With the extensive stromal expansion capacity on
      hollow fiber surfaces, the HFBR system is able to achieve high cell densities and
      3D cell-cell contacts mimicking the bone marrow microenvironment. The proposed in
      vitro system represents a dynamic and highly scalable 3D co-culture platform for
      the study of cell-stroma dependent hematopoietic/leukemic cell functions and ex
      vivo expansion.

PMID- 22161728
TI  - The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a
      randomized extension to the HORIZON-Pivotal Fracture Trial (PFT).
AB  - Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in
      postmenopausal women with osteoporosis. To investigate long-term effects of ZOL
      on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced
      Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT)
      was extended to 6 years. In this international, multicenter, double-blind,
      placebo-controlled extension trial, 1233 postmenopausal women who received ZOL
      for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n
      = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD
      percentage change from year 3 to 6 in the intent-to-treat (ITT) population.
      Secondary endpoints included other BMD sites, fractures, biochemical bone
      turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and
      dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence
      interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other
      BMD sites showed similar differences. Biochemical markers remained constant in Z6
      but rose slightly in Z3P3, remaining well below pretreatment levels in both. New
      morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n =
      30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not
      different. Significantly more Z6 patients had a transient increase in serum
      creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in
      Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p =
      0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose
      symptoms were similar in both groups. Reports of hypertension were significantly
      lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone
      density and markers in those who continued versus those who stopped treatment
      suggest residual effects, and therefore, after 3 years of annual ZOL, many
      patients may discontinue therapy up to 3 years. However, vertebral fracture
      reductions suggest that those at high fracture risk, particularly vertebral
      fracture, may benefit by continued treatment.

PMID- 22161730
TI  - Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in
      Communities (ARIC) Study, 1990-2006.
AB  - Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized
      to be, in part, explanatory. We evaluated the association between glycated
      hemoglobin, a time-integrated glycemia measure, and cancer incidence and
      mortality in nondiabetic and diabetic men and women. We conducted a prospective
      study of 12,792 cancer-free participants attending the second visit (1990-1992)
      of the Atherosclerosis Risk in Communities (ARIC) Study. We measured glycated
      hemoglobin in whole-blood samples using HPLC. Incident cancers were ascertained
      from registries and hospital records through 2006. We estimated multivariable
      adjusted hazard ratios (HR) of cancer incidence and mortality for nondiabetic
      participants with values >= 5.7% (elevated), nondiabetic participants with <5.0%
      (low) and diabetic participants all compared with nondiabetic participants with
      5.0-5.6% (normal). We ascertained 2,349 incident cancer cases and 887 cancer
      deaths. Compared with nondiabetic women with normal glycated hemoglobin,
      nondiabetic women with elevated values had an increased risk of cancer incidence
      (HR:1.24; 95% CI:1.07,1.44) and mortality (HR:1.58; 95% CI:1.23,2.05) as did
      diabetic women (incidence, HR:1.30; 95% CI:1.06,1.60, mortality, HR:1.96; 95%
      CI:1.40,2.76). Nondiabetic women with low values also had increased risk.
      Diabetic women with good glycemic control (<7.0%) had a lower cancer risk than
      those with higher values. Glycated hemoglobin in nondiabetic and diabetic men,
      and diabetes were not statistically significantly associated with total cancer
      risk. Our findings support the hypothesis that chronic hyperglycemia, even in the
      nondiabetic range, increases cancer risk in women. Maintaining normal glycated
      hemoglobin overall, and good glycemic control among diabetic adults, may reduce
      the burden of cancer, especially in women.

PMID- 22161732
TI  - Characterization of in vitro metabolites of trimethoprim and diaveridine in pig
      liver microsomes by liquid chromatography combined with hybrid ion trap/time-of
      flight mass spectrometry.
AB  - Trimethoprim (TMP) and diaveridine (DVD) are used in combination with
      sulfonamides and sulfaquinoxlaine as an effective antibacterial agent and
      antiprotozoal agent, respectively, in humans and animals. To gain a better
      understanding of the metabolism of TMP and DVD in the food-producing animals, the
      metabolites incubated with liver microsomes of pigs were analyzed for the first
      time with high-performance liquid chromatography combined with hybrid ion
      trap/time-of-flight mass spectrometry. Seven TMP-related and six DVD-related
      metabolites were characterized based on the accurate MS2 spectra and known
      structure of the parent drug, respectively. The metabolites of TMP were
      identified as two O-demethylation metabolites, a di-O-demethylation metabolite,
      two N-oxides metabolites, a hydroxylated metabolite on the methylene carbon and a
      hydroxylated metabolite on the methyl group. DVD was also biotransformed to two O
      demethylation metabolites, a di-O-demethylation metabolite, an N-oxide
      metabolite, a hydroxylation metabolite on the methylene carbon and a
      hydroxylation metabolite followed by O-demethylation. The results indicate that
      the two compounds have similar biotransformation pathways in pigs. O
      Demethylation was the major metabolic route of TMP and DVD in the pig liver
      microsomes. The proposed metabolic pathways of TMP and DVD in liver microsomes
      will provide a basis for further studies of the in vivo metabolism of the two
      drugs in food-producing animals.

PMID- 22161731
TI  - A longitudinal study of families with technology-dependent children.
AB  - Few researchers have longitudinally examined families caring for technology
      dependent children at home. We tested a theoretically and empirically based
      conceptual model by examining family functioning and normalization in 82 mothers
      (female primary caregivers) twice over 12 months. Time 1 and Time 2 cross
      sectional findings were consistent; the only predictor of family functioning was
      mothers' depressive symptoms. Contrary to the proposed model, normalization,
      caregiving duration, and home nursing hours were not directly related to family
      functioning. Baseline family functioning significantly predicted future family
      functioning. Also, mothers whose children were no longer technology-dependent at
      Time 2 reported significant improvements in family functioning and normalization.
      An intervention to address high levels of depressive symptoms of these mothers is
      essential to optimizing family functioning.

PMID- 22161734
TI  - Nucleophilic reactivities of the anions of nucleobases and their subunits.
AB  - The kinetics of the reactions of different heterocyclic anions derived from
      imidazoles, purines, pyrimidines, and related compounds with benzhydrylium ions
      and structurally related quinone methides have been studied in DMSO and water.
      The second-order rate constants (log k(2)) correlated linearly with the
      electrophilicity parameters E of the electrophiles according to the correlation
      log k(2) = s(N)(N+E) (H. Mayr, M. Patz, Angew. Chem. 1994, 106, 990-1010; Angew.
      Chem. Int. Ed. Engl. 1994, 33, 938-957) allowing us to determine the
      nucleophilicity parameters N and s(N) for these anions. In DMSO, the reactivities
      of these heterocyclic anions vary by more than six orders of magnitude and are
      comparable to carbanions, amide and imide anions, or amines. The azole anions are
      generally four to five orders of magnitude more reactive than their conjugate
      acids.

PMID- 22161735
TI  - Toward understanding transverse relaxation in human brain through its field
      dependence.
AB  - Apparent transverse-relaxation rate constants (R2+ = 1/T2+) were measured in
      various regions of the healthy human brain using a multiecho adiabatic spin-echo
      sequence at five different magnetic fields, 1.5, 1.9, 3, 4.7, and 7 T. The R2+
      values showed a clear dependence on magnetic field strength (B(0) ). The regional
      distribution of the R 2+ was well explained by the sum of three components: (1)
      regional nonhemin iron concentration ([Fe]), (2) regional macromolecular mass
      fraction (f(M) ), and (3) a region-independent factor. Accordingly, R2+ =
      alpha[Fe] + betaf(M) + gamma, where coefficients alpha, beta, and gamma were
      experimentally determined at each magnetic field by a least square fitting method
      using multiple regression analysis. Although the coefficient alpha linearly
      increased with B(0) , beta showed a quadratic dependence on top of a field
      independent component. The coefficient gamma also increased slightly with B(0) on
      top of a field-independent component. The linear dependence of alpha on B(0) was
      consistent with that observed for the transverse-relaxation rate of water protons
      in ferritin solutions as found previously by others. The quadratic dependence of
      beta on B(0) was accounted for by isochronous and anisochronous exchange
      mechanisms using intrinsic-relaxation parameters obtained from the literature.

PMID- 22161736
TI  - Direct B0 field monitoring and real-time B0 field updating in the human breast at
      7 Tesla.
AB  - Large dynamic fluctuations of the static magnetic field (B(0)) are observed in
      the human body during MR scanning, compromising image quality and detection
      sensitivity in several MR imaging and spectroscopy sequences. Partially, these
      dynamic B(0) fluctuations are due to physiological motion such as breathing, but
      other sources of temporal B(0) field fluctuations are also present in the MR
      system (e.g., eddy currents). Especially at ultrahigh field (>=7 T), the
      increased susceptibility effects lead to large B(0) field variations over time.
      Direct measurement and correction of these temporal field variations of up to 70
      Hz will lead to a significant reduction of artifacts and improved measurement
      stability/reproducibility. For direct measurement of the temporally changing B(0)
      field, a simple field probe was developed, that was placed in proximity to the
      tissue of interest. In this work, it is shown how such a field probe system can
      be used to monitor temporal B(0) field variations in the human body during MRI
      and magnetic resonance spectroscopy. Furthermore, it is shown how the acquired
      temporal B(0) field information can drive a dynamic shim module to directly
      correct the B(0) magnetic field in real time.

PMID- 22161737
TI  - [Sledge versus bicondylar surface treatment in the endoprosthetic therapy for
      unicompartmental knee arthrtitis--a comparative cost analysis].
AB  - BACKGROUND: The G-DRG system reimburses sledge endoprosthetic implantations (UKA)
      at a much lower rate than surface replacements (TKA), at significantly different
      cost weights (CW). Therefore, when only G-DRG payments are considered, the
      complete endoprosthesis implantation produces higher gains. An orientation on
      these revenues alone, however, does not provide the basis for an economically
      sound decision-making process. The aim of this study is to present a comparison
      of the variable costs of the two procedures. MATERIAL AND METHODS: The mean cost
      and performance data of 28 Endo-Model UKA implantations and of 85 NexGen CR TKA
      replacements were compared with each other in 2007. RESULTS: From the perspective
      of the hospital, when the correct medical indication is present, UKA treatment is
      of greater economic advantage. In this way the total unit contribution margin can
      be improved, and although the relative weighting is comparatively low, the costs
      are significantly lower than in a comparative analysis of the TKA. CONCLUSION:
      For the desired maximisation of the unit contribution margin, assuming that it is
      the proper medical indication, the recommendation for the hospital would be
      implantation of the UKA. Considered from the economic perspective of gains and
      costs, the assumption that a TKA would be advantageous could not be confirmed in
      the present study.

PMID- 22161738
TI  - Efficacy of iloperidone in the short-term treatment of schizophrenia: a post hoc
      analysis of pooled patient data from four phase III, placebo- and active
      controlled trials.
AB  - OBJECTIVES: The efficacy and tolerability characteristics of an antipsychotic are
      difficult to determine from a single registration study. We thus conducted an
      analysis that assessed key efficacy and tolerability outcomes post hoc from four
      pooled short-term (4-6 weeks) phase III studies that evaluated iloperidone versus
      placebo in patients with schizophrenia or schizoaffective disorder. METHODS:
      Patient-level data were pooled from four prospective, randomized, double-blind,
      placebo-controlled and active-controlled, multicenter trials of iloperidone in
      patients with schizophrenia or schizoaffective disorder aged 18-65 years.
      Iloperidone 4-8, 10-16, and 20-24 mg/day (all dosed twice daily) were compared
      with placebo. Active controls used for assay sensitivity included risperidone 4-8
      mg/day, haloperidol 15 mg/day, and ziprasidone 160 mg/day. Outcomes of interest
      were change from baseline to endpoint in the Brief Psychiatric Rating Scale
      (derived) (BPRSd), Positive and Negative Syndrome Scale (PANSS)-total (PANSS-T)
      score, and PANSS-positive (PANSS-P) and PANSS-negative (PANSS-N) subscale scores.
      An analysis of covariance (with treatment and study as factors, baseline as a
      covariate) was performed to compare changes between the iloperidone treatment
      groups versus placebo, on the basis of a last-observation-carried-forward
      approach for the intent-to-treat (ITT) populations. Tolerability outcomes were
      obtained from spontaneously reported adverse events (AEs), and number needed to
      harm was calculated for each antipsychotic versus placebo for the total
      population. RESULTS: The ITT population included both schizoaffective and
      schizophrenia patients (N = 2401): n = 370, n = 494, and n = 424 for iloperidone
      4-8, 10-16, and 20-24 mg/day, respectively; n = 294 for risperidone; n = 114 for
      haloperidol; n = 144 for ziprasidone; and n = 561 for placebo. Treatment with
      iloperidone 10-16 mg/day or 20-24 mg/day was associated with significantly
      improved BPRSd, PANSS-T, PANSS-P, and PANSS-N scores versus treatment with
      placebo. When only patients with schizophrenia were included (n = 1941), the
      pattern of results was essentially unchanged. The active controls confirmed assay
      sensitivity. Across all iloperidone dose groups, the incidences of extrapyramidal
      disorders and akathisia were similar to those observed with placebo. AEs for
      which the frequency was greater for iloperidone than placebo and for which the
      95% confidence interval for number needed to harm did not contain infinity were
      dizziness, dry mouth, somnolence, nasal congestion, fatigue, sedation, and
      tachycardia; in general, for these AEs, frequency was higher with higher doses,
      resulting in a lower number needed to harm. CONCLUSIONS: Consistent with product
      labeling, iloperidone 10-16 mg/day or 20-24 mg/day demonstrated significant
      improvement over placebo on BPRSd and PANSS-T scores, as well as on PANSS-P and
      PANSS-N subscale scores over 6 weeks of treatment in patients with schizophrenia
      and in the ITT population, which includes patients with schizoaffective disorder.
      Iloperidone did not differ from placebo in terms of extrapyramidal disorders and
      akathisia.

PMID- 22161739
TI  - Biowaiver monographs for immediate-release solid oral dosage forms: primaquine
      phosphate.
AB  - Literature data relevant to the decision to allow a waiver of in vivo
      bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral
      dosage forms containing the antimalarial drug primaquine phosphate as the only
      active pharmaceutical ingredient (API) are reviewed. On the basis of permeability
      data and solubility studies, primaquine phosphate was found to be "highly
      soluble" and "highly permeable" API, thus conforming to Class I of the
      Biopharmaceutical Classification System (BCS). It has a wide therapeutic index.
      BCS-conform dissolution studies showed the products to be rapidly dissolving. No
      data pertaining to BE or bioinequivalence of IR primaquine phosphate products
      could be located in open literature. On the basis of the available data, a
      biowaiver-procedure-based approval can be recommended for IR solid oral dosage
      forms of primaquine phosphate, provided the generic product contains excipients
      present in products already approved by the International Conference on
      Harmonisation or associated countries in similar amounts and the test and
      reference products meet the dissolution criteria for "rapidly dissolving" (>85%
      drug release in 30 min in standard media at pH 1.2, 4.5, and 6.8; similarity
      factor (f(2)) > 50) or "very rapidly dissolving" products (>85% drug release in
      15 min in standard media at pH 1.2, 4.5, and 6.8).

PMID- 22161740
TI  - New triterpenoids from the leaves of Cyclocarya paliurus.
AB  - Six new triterpenoids including four new secodammarane triterpenoid glycosides (1
      4), an epoxydammarane triterpenoid glycoside (5), and a new secodammarane
      triterpenoid (6) were isolated from the ethanolic extract of the leaves of
      Cyclocarya paliurus. The structures of these compounds were elucidated by
      spectroscopic analysis methods. Compounds 1-6 were evaluated for their inhibitory
      activities against alpha-glucosidase, lipase, DPP-IV, and aldose reductase.

PMID- 22161741
TI  - How to deal with double partial verification when evaluating two index tests in
      relation to a reference test?
AB  - Research into the diagnostic accuracy of clinical tests is often hampered by
      single or double partial verification mechanisms, that is, not all patients have
      their disease status verified by a reference test, neither do all patients
      receive all tests under evaluation (index tests). We show methods that reduce
      verification bias introduced when omitting data from partially tested patients.
      Adjustment techniques are well established when there are no missing index tests
      and when the reference test is 'missing at random'. However, in practice, index
      tests tend to be omitted, and the choice of applying a reference test may depend
      on unobserved variables related to disease status, that is, verification may be
      missing not at random (MNAR). We study double partial verification in a clinical
      example from reproductive medicine in which we analyse the diagnostic values of
      the chlamydia antibody test and the hysterosalpingography in relation to a
      diagnostic laparoscopy. First, we plot all possible combinations of sensitivity
      and specificity of both index tests in two test ignorance regions. Then, we
      construct models in which we impose different assumptions for the verification
      process. We allow for missing index tests, study the influence of patient
      characteristics and study the accuracy estimates if an MNAR mechanism would
      operate. It is shown that data on tests used in the diagnostic process of the
      same population are preferably studied jointly and that the influence of an MNAR
      verification process was limited in a clinical study where more than half of the
      patients did not have the reference test.

PMID- 22161742
TI  - Advancing rheumatology: mission possible.

PMID- 22161743
TI  - Electronic structure and symmetry in conjugated pi-electron systems.
AB  - The continuous symmetry measures (CSM) method has been used to study the pi
      electron systems for a diverse set of molecules, illustrating the capabilities of
      this new analytical tool to quantify the changes in the electronic structure of
      molecules upon symmetry breaking perturbations induced either by geometry
      modifications or chemical substitutions. The symmetry analysis applied to the
      Hamiltonian, the molecular orbitals or the electron density obtained from a
      simple Huckel model for these compounds reveals the basic relations between
      symmetry and the electronic structure. Calculation of continuous symmetry
      measures from ab initio calculations confirms these relations, allowing at the
      same time a much more accurate description of the influence of symmetry on the
      electronic structure of these compounds.

PMID- 22161744
TI  - Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of
      oral tongue squamous cell carcinoma.
AB  - Enhancer of Zeste homolog 2 (EZH2) is a critical component of the polycomb
      repressive complex 2 (PRC2) that regulates many essential biological processes,
      including embryogenesis and many developmental events. The oncogenic role of EZH2
      has recently been implicated in several cancer types. In this study, we first
      confirmed that the over-expression of EZH2 is a frequent event in oral tongue
      squamous cell carcinoma (OTSCC). We further demonstrated that EZH2 over
      expression is correlated with advanced stages of the disease and is associated
      with lymph node metastasis. Statistical analysis revealed that EZH2 over
      expression was correlated with reduced overall survival. Furthermore, over
      expression of EZH2 was correlated with reduced expression of tumor suppressor
      gene E-cadherin. These observations were confirmed in vitro, in which knockdown
      of EZH2-induced E-cadherin expression and reduced cell migration and invasion. In
      contrast, ectopic transfection of EZH2 led to reduced E-cadherin expression and
      enhanced cell migration and invasion. Furthermore, EZH2 may act on cell migration
      in part by suppressing the E-cadherin expression. Taken together, these data
      suggest that EZH2 plays major roles in the progression of OTSCC, and may serve as
      a biomarker or therapeutic target for patients at risk of metastasis.

PMID- 22161745
TI  - Grand challenge competition to predict in vivo knee loads.
AB  - Impairment of the human neuromusculoskeletal system can lead to significant
      mobility limitations and decreased quality of life. Computational models that
      accurately represent the musculoskeletal systems of individual patients could be
      used to explore different treatment options and optimize clinical outcome. The
      most significant barrier to model-based treatment design is validation of model
      based estimates of in vivo contact and muscle forces. This paper introduces an
      annual "Grand Challenge Competition to Predict In Vivo Knee Loads" based on a
      series of comprehensive publicly available in vivo data sets for evaluating
      musculoskeletal model predictions of contact and muscle forces in the knee. The
      data sets come from patients implanted with force-measuring tibial prostheses.
      Following a historical review of musculoskeletal modeling methods used for
      estimating knee muscle and contact forces, we describe the first two data sets
      used for the first two competitions and summarize four subsequent data sets to be
      used for future competitions. These data sets include tibial contact force, video
      motion, ground reaction, muscle EMG, muscle strength, static and dynamic imaging,
      and implant geometry data. Competition participants create musculoskeletal models
      to predict tibial contact forces without having access to the corresponding in
      vivo measurements. These blinded predictions provide an unbiased evaluation of
      the capabilities and limitations of musculoskeletal modeling methods. The paper
      concludes with a discussion of how these unique data sets can be used by the
      musculoskeletal modeling research community to improve the estimation of in vivo
      muscle and contact forces and ultimately to help make musculoskeletal models
      clinically useful.

PMID- 22161746
TI  - The effect of family-based multidisciplinary cognitive behavioral treatment on
      health-related quality of life in childhood obesity.
AB  - PURPOSE: To evaluate the effect of multidisciplinary treatment on obesity and
      health-related quality of life (HRQOL). METHODS: Obese children were randomized
      to a multidisciplinary lifestyle treatment, including medical, nutritional,
      physical, and psychological counseling during 3 months, (n = 40, BMI-SDS; 4.2 +/-
      0.7, age; 13.3 +/- 2.0) or standard care, including an initial advice on
      nutrition and physical activity by the pediatrician (n = 39, BMI-SDS; 4.3 +/-
      0.7, age; 13.1 +/- 1.9). At baseline, after 3 months of treatment and at 12
      months follow-up, data were collected for BMI-SDS and a European validated
      questionnaire for assessing HRQOL (DISABKIDS). RESULTS: A significantly reduced
      BMI-SDS was found for the intervention group after 3 months treatment (4.0 +/-
      0.9 vs. 4.2 +/- 0.7, P = 0.02) and at 12 months follow-up (3.8 +/- 1.1 vs. 4.2 +/
      0.7, P = 0.03). HRQOL in the intervention group was significantly improved at 12
      months follow-up and unchanged in the obese control group. Agreement between
      child and parent report was moderate (67-85%), with parents reporting a lower
      HRQOL for their obese children than children themselves in both groups.
      CONCLUSION: Multidisciplinary treatment is effective in reducing BMI-SDS and
      improving HRQOL after 12 months follow-up.

PMID- 22161747
TI  - Chemoprevention of mouse lung and colon tumors by suberoylanilide hydroxamic acid
      and atorvastatin.
AB  - Atorvastatin and suberoylanilide hydroxamic acid (SAHA) were evaluated for
      chemoprevention of mouse lung tumors. In Experiment 1, lung tumors were induced
      by vinyl carbamate in strain A/J mice followed by 500 mg/kg SAHA, 60 or 180 mg/kg
      atorvastatin, and combinations containing SAHA and atorvastatin administered in
      their diet. SAHA and both combinations, but not atorvastatin, decreased the
      multiplicity of lung tumors, including large adenomas and adenocarcinomas with
      the combinations demonstrating the greatest efficacy. In Experiment 2, lung
      tumors were induced by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol in strain
      A/J mice followed by 180 mg/kg atorvastatin, 500 mg/kg SAHA, or both drugs
      administered in the diet. SAHA and the combination of both drugs, but not
      atorvastatin alone, decreased the multiplicity of lung tumors and large tumors,
      with the combination demonstrating greater efficacy. In Experiment 3, lung tumors
      were induced by 1,2-dimethylhydrazine in Swiss-Webster mice followed by 160 mg/kg
      atorvastatin, 400 mg/kg SAHA, or a combination of both drugs administered in the
      diet. SAHA and the combination, but not atorvastatin, decreased the multiplicity
      of lung tumors with the combination demonstrating greater efficacy. The
      multiplicity of colon tumors was decreased by SAHA, atorvastatin, and the
      combination, without any significant difference in their efficacy. mRNA
      expression analysis of lung tumor bearing mice suggested that the enhanced
      chemopreventive activity of the combination is related to atorvastatin modulation
      of DNA repair, SAHA modulation of angiogenesis, and both drugs modulating
      invasion and metastasis pathways. Atorvastatin demonstrated chemoprevention
      activity as indicated by the enhancement of the efficacy of SAHA to prevent mouse
      lung tumors.

PMID- 22161748
TI  - Significant deterioration in nanomechanical quality occurs through incomplete
      extrafibrillar mineralization in rachitic bone: evidence from in-situ synchrotron
      X-ray scattering and backscattered electron imaging.
AB  - Bone diseases such as rickets and osteoporosis cause significant reduction in
      bone quantity and quality, which leads to mechanical abnormalities. However, the
      precise ultrastructural mechanism by which altered bone quality affects
      mechanical properties is not clearly understood. Here we demonstrate the
      functional link between altered bone quality (reduced mineralization) and
      abnormal fibrillar-level mechanics using a novel, real-time synchrotron X-ray
      nanomechanical imaging method to study a mouse model with rickets due to reduced
      extrafibrillar mineralization. A previously unreported N-ethyl-N-nitrosourea
      (ENU) mouse model for hypophosphatemic rickets (Hpr), as a result of missense
      Trp314Arg mutation of the phosphate regulating gene with homologies to
      endopeptidase on the X chromosome (Phex) and with features consistent with X
      linked hypophosphatemic rickets (XLHR) in man, was investigated using in situ
      synchrotron small angle X-ray scattering to measure real-time changes in axial
      periodicity of the nanoscale mineralized fibrils in bone during tensile loading.
      These determine nanomechanical parameters including fibril elastic modulus and
      maximum fibril strain. Mineral content was estimated using backscattered electron
      imaging. A significant reduction of effective fibril modulus and enhancement of
      maximum fibril strain was found in Hpr mice. Effective fibril modulus and maximum
      fibril strain in the elastic region increased consistently with age in Hpr and
      wild-type mice. However, the mean mineral content was ~21% lower in Hpr mice and
      was more heterogeneous in its distribution. Our results are consistent with a
      nanostructural mechanism in which incompletely mineralized fibrils show greater
      extensibility and lower stiffness, leading to macroscopic outcomes such as
      greater bone flexibility. Our study demonstrates the value of in situ X-ray
      nanomechanical imaging in linking the alterations in bone nanostructure to
      nanoscale mechanical deterioration in a metabolic bone disease.

PMID- 22161749
TI  - Quantitative in vivo diffusion imaging of cartilage using double echo steady
      state free precession.
AB  - Single-shot echo-planar imaging techniques are commonly used for diffusion
      weighted imaging (DWI) but offer rather poor spatial resolution and field-of-view
      coverage for species with short T(2) . In contrast, steady-state free precession
      (SSFP) has shown promising results for DWI of the musculoskeletal system, but
      quantification is generally hampered by its prominent sensitivity on relaxation
      times. In this work, a new and truly diffusion-weighted (that is relaxation time
      independent) SSFP DWI technique is introduced using a double-echo steady-state
      approach. Within this framework (and this is in contrast to common SSFP DWI
      techniques using SSFP-Echo) both primary echo paths of nonbalanced SSFP are
      acquired, namely the FID and the Echo. Simulations and in vitro measurements
      reveal that the ratio of the Echo/FID signal ratios of two double-echo steady
      state scans acquired with and without diffusion sensitizing dephasing moments
      provides a highly relaxation independent quantity for diffusion quantification.
      As a result, relaxation-independent high-resolution (0.4 * 0.4 - 0.6 * 0.6 mm(2)
      in-plane resolution) quantitative in vivo SSFP DWI is demonstrated for human
      articular cartilage using diffusion-weighted double-echo steady-state scans in
      the knee and ankle joint at 3.0 T. The derived diffusion coefficients for
      cartilage (D ~ 1.0-1.5 MUm(2) /ms) and synovial fluid (D ~ 2.6 MUm(2) /ms) are in
      agreement with previous work.

PMID- 22161751
TI  - [Pitfalls of the current laboratory diagnosis and treatment  of vulvovaginal
      candidiasis].
AB  - Vulvovaginal candidiasis remains one of the most frequently diagnosed
      inflammatory diseases of the vagina, which affects most sexually active women. In
      most patients, it is manifested as acute inflammation which is easy to diagnose
      and treat. However, in the susceptible population, it may be characterized by
      recurrent episodes, usually with an unknown cause or exacerbating moment. These
      facts complicate the diagnosis and therapy. This is highlighted by both non
      specific symptoms shared with many other vaginal infections and paucity of
      reliable signs for diagnosis. Under these circumstances, it is difficult to
      associate vaginal complaints with yeasts and, vice versa, the presence of yeasts
      does not necessarily confirm fungal aetiology. Therefore, it is better to regard
      the condition as a syndrome and the chronic problems as vulvovaginal discomfort.
      It is a prerequisite for an unbiased diagnostic approach, increasing the
      probability of finding the real cause of the problem and the chances of treating
      or even curing the disease. The article is concerned with controversial and
      problematic aspects of diagnosis and treatment of vulvovaginal candidiasis with a
      focus on laboratory diagnosis, terminology, epidemiology and ecology of yeasts in
      relation to vaginal microbiota and, last but not least, on alternative
      therapeutic approaches.

PMID- 22161750
TI  - Cognitive functioning after cancer treatment: a 3-year longitudinal comparison of
      breast cancer survivors treated with chemotherapy or radiation and noncancer
      controls.
AB  - BACKGROUND: This study examined the influence of prior treatment on the course of
      cognitive functioning in breast cancer survivors. Changes in cognitive
      functioning over time were compared in breast cancer survivors treated with
      chemotherapy plus radiotherapy, breast cancer survivors treated with radiotherapy
      only, and women with no history of cancer. METHODS: Stage 0-II breast cancer
      patients treated with chemotherapy plus radiotherapy (CT group; n = 62) or
      radiotherapy only (RT group; n = 67) completed neuropsychological assessments 6
      months after completing treatment and again 36 months later. Women with no
      history of cancer (NC group; n = 184) were assessed over a similar interval.
      RESULTS: A significant group * time effect was found for processing speed (P =
      .009) that reflected a tendency for the NC group but not the RT and CT groups to
      improve over time. There was also a significant group effect for executive
      functioning (P = .006) that reflected the NC group performing better than the CT
      and RT groups. Additional analyses found the administration of hormonal therapy
      was not associated with change over time in cognitive performance. CONCLUSIONS:
      Findings provide limited support for the view that changes in cognitive
      functioning in cancer survivors are attributable to chemotherapy administration
      and illustrate the importance of including a radiotherapy comparison group.
      Future research should seek to examine possible mechanisms that could explain the
      apparent prolonged impact of both chemotherapy and radiotherapy on cognitive
      functioning in breast cancer survivors.

PMID- 22161752
TI  - [Microbiological and clinical aspects of tularaemia].
AB  - Francisella tularensis belongs to the most important biological agents
      potentially applicable in biological warfare and bioterrorism. High virulence,
      easy and rapid spread among individual vectors, stability of the cells in aerosol
      and good penetration into the lungs make F. tularensis one of the most important
      biological warfare agents in both human and veterinary medicine. The text
      provides comprehensive data about tularaemia and outlines the fate of the
      pathogen in the host. Special attention is paid to immunological aspects of the
      disease, therapy, and diagnostic methods.

PMID- 22161753
TI  - [Incidence of leptospirosis in Pardubice and Hradec Kralove region and a part of
      Vysocina region in the years 2002-2009].
AB  - BACKGROUND: The aim of this study was to evaluate the incidence of leptospirosis
      in Pardubice and Hradec Kralove regions and a part of Vysocina region in 2002
      2009. A group of patients was statistically analyzed and the incidence rates of
      leptospirosis in individual months and years were calculated. MATERIAL AND
      METHODS: A group of 4,813 patients with suspected leptospirosis from Pardubice
      and Hradec Kralove regions and a part of Vysocina region were examinated in our
      centre in 2002-2009. A total of 5,366 biological samples were studied. From 4,625
      blood samples, 3,958 were examinated with the serological microagglutination
      lysis method and the remaining 667 with the PCR method. RESULTS: From 4,813
      patients suspected to have leptospirosis, 89 were found to be leptospirosis
      positive. Leptospirosis was diagnosed in 63 males (70.7 %) a 26 females (29.3 %);
      the mean age were 39.52 +/- 17.67 years in males and 46.85 +/- 18.34 years in
      females; the mean age men + women was 41.66 +/- 18.13 years (range 3-78 years).
      Most positive male patients (n = 28) were in 26-45 age group; the findings were
      similar in females (n = 10). The highest number of leptospirosis cases was noted
      in 2005. Most frequently, infection caused by pathogenic leptospires was
      diagnosed in November. CONCLUSION: The incidence rates of leptospirosis in
      Pardubice and Hradec Kralove regions and a part of Vysocina region in 2002-2009
      (with the exception of 2008) exceeded the overall reported levels 0.4/100,000
      population.

PMID- 22161754
TI  - [Comparison of results of two serological methods for diagnosing leptospirosis -
      microagglutination test and ELISA].
AB  - BACKGROUND: The aim of this study was to evaluate diagnostic sensitivity and
      specificity of the SERION ELISA classic IgM and SERION ELISA classic IgG kits and
      to confirm the results by the microagglutination test (MAT). MATERIAL AND
      METHODS: A total of 45 blood serum samples from 45 patients, 30 from males and 15
      from females (mean age 44.24 +/- 15.56 range 19-82 year), were included in our
      study. Blood serum samples were examined using the ELISA and MAT methods and
      diagnostic sensitivity and specificity of both methods were calculated. RESULTS:
      The MAT was shown to have 100 % diagnostic sensitivity and specificity. The ELISA
      kits for detecting IgM and IgG antibodies against pathogenic leptospires had
      diagnostic sensitivity of 100 % and diagnostic specificity of 88.6 % and 54.3 %,
      respectively. CONCLUSION: The above results suggest that the MAT with diagnostic
      sensitivity and specificity of 100 % remains the gold standard for detection of
      specific antibodies against pathogenic leptospires. The diagnostic sensitivity of
      both ELISA kits is high but due to their low diagnostic specificity, especially
      in the case of IgG antibodies, the kits are inappropriate for use in routine
      clinical practice.

PMID- 22161755
TI  - [Monitoring the prevalence of pathogenic Borrelia burgdorferi sensu lato in ticks
      in two Brno locations].
AB  - OBJECTIVE: The aim of the article is to present the results of monitoring the
      prevalence of the spirochete Borrelia burgdorferi sensu lato (Bbsl) in Ixodes
      ricinus ticks in two different locations in the city of Brno, Pisarky and
      Zamilovany hajek (ZH). At the same time, factors potentially affecting the
      activity of ticks in these locations were studied. Results of the monitoring
      carried out in the first three spring months of the year 2011 are compared with
      2010 results. MATERIAL AND METHODS: In 2010-2011, Ixodes ricinus ticks were
      periodically sampled in two locations in Brno by flagging. Ticks were
      investigated by dark field microscopy (DFM) for the presence of spirochetes. DFM
      positive samples from 2010 were tested by PCR to identify Bbsl. RESULTS: In the
      first three spring months (March-May) of 2011, a total of 234 ticks were
      collected in Pisarky and 211 ticks in ZH. Positive samples detected by DFM
      accounted for 5.56 % in Pisarky and 25.12 % in ZH. PCR confirmed Bbsl in at least
      75 %. Statistical analysis confirmed the dependence of tick activity on the air
      temperature in both locations. CONCLUSION: Within the same city, seroprevalence
      was found to be different in two locations. High seroprevalence in ZH (25.12 %)
      could be attributed to focal spread of the disease from several sources, both
      ticks and reservoirs such as rodents. This may results in unfavourable
      epidemiological situation in Brno. On the other hand, the seroprevalence rates in
      Pisarky are consistent with findings from an earlier long-term study.

PMID- 22161757
TI  - Developmental status and home environment among children born to immigrant women
      married to Taiwanese men.
AB  - The aims of this cross-sectional study were to examine (a) the developmental
      status and home environments of children (6-24 months) of immigrant women married
      to Taiwanese men, and (b) the association of child developmental status with
      parental socio-demographics, maternal language abilities, and home environment
      qualities. Participants were 61 children and their mothers from China and
      Vietnam. Data were collected with interviews, home observations, and
      developmental testing. The children had lower cognitive and language but higher
      motor and social development scores compared with native norms. Home environment
      and maternal perceived language ability were positively associated with child
      development. The association of home environment and maternal language ability
      with early childhood development was supported for immigrant populations in
      Taiwan.

PMID- 22161756
TI  - Phenethyl isothiocyanate suppresses inhibitor of apoptosis family protein
      expression in prostate cancer cells in culture and in vivo.
AB  - BACKGROUND: Cruciferous vegetable constituent phenethyl isothiocyanate (PEITC)
      causes apoptosis in prostate cancer cells through mechanisms not fully
      understood. The present study was designed to determine the role of inhibitor of
      apoptosis (IAP) family proteins in PEITC-induced apoptosis induction. METHODS:
      Effect of PEITC treatment on protein and mRNA expression of IAP in cells was
      determined by Western blotting and reverse transcription PCR, respectively.
      Immunohistochemistry was performed to determine the in vivo effect of PEITC
      administration on X-linked IAP (XIAP) and Survivin protein expression.
      Overexpression of desired protein was achieved by transient transfection. Cell
      viability was determined by trypan blue dye exclusion assay, whereas apoptosis
      was quantified by measurement of histone-associated DNA fragment release into the
      cytosol. Transwell chamber assay was used to determine cell migration. RESULTS:
      Exposure of PC-3 and LNCaP human prostate cancer cells to PEITC resulted in
      downregulation of XIAP and Survivin proteins and Survivin mRNA. PEITC
      administration to transgenic adenocarcinoma of mouse prostate mice caused modest
      but significant downregulation of XIAP and Survivin proteins in the dorsolateral
      prostate. Proapoptotic response to PEITC was significantly attenuated by ectopic
      expression of XIAP and Survivin proteins. Survivin overexpression also conferred
      modest but significant protection against PEITC-mediated inhibition of PC-3 cell
      migration. CONCLUSIONS: The present study demonstrates that cellular responses to
      PEITC, including apoptosis induction and inhibition of cell migration, in
      prostate cancer cells are mediated by downregulation of XIAP and/or Survivin,
      which may serve as valid biomarkers of PEITC response in future clinical
      investigations.

PMID- 22161758
TI  - Racial/ethnic differences in serious psychological distress among older adults in
      California.
AB  - OBJECTIVES: This study examined racial/ethnic differences in the prevalence and
      correlates of past year serious psychological distress ([SPD] defined as having a
      score of 13 or higher on the K6 scale), as well as impairments caused by SPD
      among older adults in California. METHODS: Data drawn from the 2007 California
      health interview survey, representing racially/ethnically diverse adults 65 years
      and older, were analyzed: whites, African Americans, Latinos, Asians, and
      American Indians/Alaska Natives. Using weighted data, descriptive analyses for
      prevalence rates and logistic regression analyses were conducted. RESULTS: The
      prevalence of past year SPD was significantly different across the five
      racial/ethnic groups (p = 0.000), with American Indians/Alaska Natives having the
      highest prevalence (18.2%) and Asians having the lowest prevalence (2.6%).
      Disability was significantly associated with prevalence of SPD in all five
      racial/ethnic groups (all ps < 0.05). Impairments caused by past year SPD did not
      significantly differ across the five racial/ethnic groups, but overall functional
      impairments caused by SPD were highest among whites and lowest among Latinos.
      Racial/ethnic-specific correlates of past year SPD for Asians were lower
      educational attainment (OR = 0.71, 95% CI = 0.55-0.92) and for African Americans,
      a greater number of chronic diseases (OR = 2.35, 95% CI = 1.55-3.54).
      CONCLUSIONS: Apparent racial/ethnic differences existed in the prevalence and
      correlates of past year SPD among older adults in California. The findings
      suggest that different disease burden caused by SPD may exist across diverse
      racial/ethnic elderly groups and highlight the need to develop race/ethnicity
      specific intervention strategies.

PMID- 22161760
TI  - Rapid virological response: is it four or eight weeks?

PMID- 22161761
TI  - Down-regulation of microRNA-34a* in rheumatoid arthritis synovial fibroblasts
      promotes apoptosis resistance.
AB  - OBJECTIVE: To investigate the expression and effect of the microRNA-34 (miR-34)
      family on apoptosis in rheumatoid arthritis synovial fibroblasts (RASFs).
      METHODS: Expression of the miR-34 family in synovial fibroblasts with or without
      stimulation with Toll-like receptor (TLR) ligands, tumor necrosis factor alpha
      (TNFalpha), interleukin-1beta (IL-1beta), hypoxia, or 5-azacytidine was analyzed
      by real-time polymerase chain reaction (PCR). Promoter methylation was studied by
      combined bisulfite restriction analysis. The effects of overexpression and
      silencing of miR-34a and miR-34a* on apoptosis were analyzed by annexin
      V/propidium iodide staining. Production of X-linked inhibitor of apoptosis
      protein (XIAP) was assessed by real-time PCR and immunohistochemistry analysis.
      Reporter gene assay was used to study the signaling pathways of miR-34a*.
      RESULTS: Basal expression levels of miR-34a* were found to be reduced in synovial
      fibroblasts from RA patients compared to osteoarthritis patients, whereas levels
      of miR-34a, miR-34b/b*, and miR-34c/c* did not differ. Neither TNFalpha, IL
      1beta, TLR ligands, nor hypoxia altered miR-34a* expression. However, we
      demonstrated that the promoter of miR-34a/34a* was methylated and showed that
      transcription of the miR-34a duplex was induced upon treatment with demethylating
      agents. Enforced expression of miR-34a* led to an increased rate of FasL- and
      TRAIL-mediated apoptosis in RASFs. Moreover, levels of miR-34a* were highly
      correlated with expression of XIAP, which was found to be up-regulated in RA
      synovial cells. Finally, we identified XIAP as a direct target of miR-34a*.
      CONCLUSION: Our data provide evidence of a methylation-specific down-regulation
      of proapoptotic miR-34a* in RASFs. Decreased expression of miR- 34a* results in
      up-regulation of its direct target XIAP, thereby contributing to resistance of
      RASFs to apoptosis.

PMID- 22161762
TI  - Pharmacokinetic comparisons of albiflorin and paeoniflorin after oral
      administration of Shaoyao-Gancao-Tang and single herb Paeony decoction to rats.
AB  - Shaoyao-Gancao-Tang (SGT) is a traditional Chinese prescription containing Radix
      Paeoniae alba and Radix Glycyrrhizae and is commonly used to relieve pains.
      Albiflorin and paeoniflorin are the main effective compounds of Radix Paeoniae
      alba, and the pharmacokinetic differences of the two compounds in rats after oral
      administration of SGT and single herb Paeony decoction were studied. At different
      time points (5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, and 540 min)
      after administration, plasma concentrations of albiflorin and paeoniflorin were
      determined using a simple and reliable UPLC method, and main pharmacokinetic
      parameters were evaluated. It was found that there were significant differences
      (p < 0.05 or p < 0.01) between the two groups. The results indicated that some
      components in the other ingredient herb of SGT (Radix Glycyrrhizae) had a
      pharmacokinetic interaction with albiflorin and paeoniflorin and hence reduced
      their systematic exposure level.

PMID- 22161763
TI  - Isolation and bioactivity evaluation of terpenoids from the medicinal fungus
      Ganoderma sinense.
AB  - A new pentanorlanostane, ganosineniol A (1), eight new lanostane triterpenoids,
      ganosinoside A (2), ganoderic acid Jc (3), ganoderic acid Jd (4),
      ganodermatetraol (5), ganolucidic acid gammaa (6), ganolucidate F (7), ganoderiol
      J ( 8), and methyl lucidenate Ha ( 9), and a new sesquiterpenoid, ganosinensine
      (10), together with eleven known triterpenoids (11- 21), were isolated from the
      fruiting bodies of the fungus Ganoderma sinense. Chemical structures were
      determined based on spectroscopic evidence, including 1D, 2D NMR, and mass
      spectral data. Furthermore, all isolates were tested for cytotoxic activity and
      induction ability of hPXR-mediated CYP3A4 expression. Among them, ganoderic acid
      Jc (3) displayed selective inhibitory activity against HL-60 cells (IC50 = 8.30
      uM), and ganoderiol E (11) exhibited selective cytotoxic activity against MCF-7
      cells (IC50 = 6.35 uM). Meanwhile, compounds 5, 7, and ganolucidic acids B and C
      (19, 20) showed induction ability of hPXR-mediated CYP3A4 expression.

PMID- 22161764
TI  - Investigating the effect of Aloe vera gel on the buccal permeability of
      didanosine.
AB  - The buccal mucosal route offers several advantages but the delivery of certain
      drugs can be limited by low membrane permeability. This study investigated the
      buccal permeability properties of didanosine (ddI) and assessed the potential of
      Aloe vera gel (AVgel) as a novel buccal permeation enhancer. Permeation studies
      were performed using Franz diffusion cells, and the drug was quantified by UV
      spectroscopy. Histomorphological evaluations were undertaken using light and
      transmission electron microscopy. The permeability of ddI was concentration
      dependent, and it did not have any adverse effects on the buccal mucosae. A
      linear relationship (R2 = 0.9557) between the concentrations and flux indicated
      passive diffusion as the mechanism of drug transport. AVgel at concentrations of
      0.25 to 2 %w/v enhanced ddI permeability with enhancement ratios from 5.09 (0.25
      %w/v) to 11.78 (2 %w/v) but decreased permeability at 4 and 6 %w/v.
      Ultrastructural analysis of the buccal mucosae treated with phosphate buffer
      saline pH 7.4 (PBS), ddI/PBS, and ddI/PBS/AVgel 0.5 %w/v showed cells with normal
      plasmalemma, well-developed cristae, and nuclei with regular nuclear envelopes.
      However, cells from 1, 2, and 6 %w/v AVgel-treated mucosae showed irregular
      nuclear outlines, increased intercellular spacing, and plasmalemma crenulations.
      This study demonstrates the potential of AVgel as a buccal permeation enhancer
      for ddI to improve anti-HIV and AIDS therapy.

PMID- 22161765
TI  - Hierarchical TiO2 microspheres: synergetic effect of {001} and {101} facets for
      enhanced photocatalytic activity.
AB  - Well-faceted nanocrystals of anatase TiO(2) with specific reactive facets have
      attracted extraordinary research interest due to their many intrinsic shape
      dependent properties. In this work, hierarchical TiO(2) microspheres consisting
      of anatase nanosheets or decahedrons were synthesized by means of a facile
      hydrothermal technique; meanwhile, the percentage of {001} facets can be tuned
      from 82 to 45%. Importantly, by investigating the photo-oxidation reactions for
      OH radical generation and photoreduction reactions for hydrogen evolution, the
      TiO(2) microspheres consisting of nano-decahedrons with 45% {001} facets show
      superior photoreactivity (more than 4.8-times) compared to the nanosheets with
      82% {001} facets. By analyzing the results of scanning electron microscopy (SEM),
      photoluminescence (PL) and first-principles density functional theory (DFT)
      calculations, a model of charge separation between the well-formed {001} and
      {101} facets is proposed, and the enhanced photocatalytic efficiency is largely
      attributed to the efficient separation of photogenerated charges among the
      crystal facets co-exposed.

PMID- 22161766
TI  - Association of the miR-146aC>G, 149C>T, 196a2C>T, and 499A>G polymorphisms with
      colorectal cancer in the Korean population.
AB  - MicroRNAs (miRNAs) are small, 18- to 22-nucleotide non-coding RNAs that regulate
      target gene expression. Although recent studies focused on various diseases that
      harbor the miR-146aC>G (rs2910164), 149C>T (rs2292832), 196a2C>T (rs11614913),
      and 499A>G (rs3746444) polymorphisms, the role of miRNA genetic variants in
      colorectal cancer is still unknown. The present study aimed to evaluate the role
      of four miRNA polymorphisms in patients with colorectal cancer. We enrolled 446
      colorectal cancer patients and 502 control subjects from the Korean population.
      We found a significantly increased colorectal cancer risk with the miR-196a2CC
      genotype compared with the TT/CT genotype (AOR = 1.50; 95% CI = 1.11-2.04; P =
      0.01; FDR-P = 0.04). In the stratified analyses, we observed both weak and strong
      association data. We found stronger associations of the miR-196a2 variants in the
      non-diabetic and rectal cancer groups than other stratified groups. Our data
      suggest that the miRNA variants could affect the development of colorectal cancer
      in the Korean population.

PMID- 22161767
TI  - The origins of enantioselectivity in Rh-diene complex catalysed arylation of
      cyclohex-2-enones.

PMID- 22161768
TI  - Effect of atorvastatin on the cortical bones of corticosteroid treated rabbits.
AB  - Osteoporosis ("secondary" osteoporosis) and avascular necrosis (AVN) of the
      femoral head are well-known adverse effects of corticosteroid therapy. Statins
      have been reputed to increase bone strength and bone density. In this study, we
      evaluated the effect of atorvastatin calcium on the flexural properties (3-point
      bending strength and modulus) of corticosteroid (methylprednisolone acetate)
      treated rabbit femurs and tibias. Our study hypothesis was that the use of
      statins would counteract the loss of bone strength caused by corticosteroid
      treatment. The 40 rabbits were divided into 5 groups: control, corticosteroid
      alone and corticosteroid combined with oral doses of atorvastatin calcium (2, 10,
      or 20 mg/day). A daily oral dose of atorvastatin calcium treatment for 70 days
      weakened the long bones of methylprednisolone acetate treated rabbits
      irrespective of the dosage (2, 10, or 20 mg). Cortical bone strength was assessed
      using the 3-point bending test at the end of the study period. A daily oral dose
      of atorvastatin calcium did not attenuate the loss of cortical bone strength
      caused by corticosteroid treatment in rabbits. It appeared to decrease that bone
      strength. If these results hold true in humans, they would have wide
      applicability given the frequent combined use of corticosteroids and statins in
      many patients.

PMID- 22161769
TI  - Performance of binary markers for censored failure time outcome: nonparametric
      approach based on proportions.
AB  - This work focuses on the assessment of the discrimination ability of a binary
      marker to identify patients that will relapse in time. We consider the cumulative
      definition of sensitivity and dynamic definition of specificity at a time
      horizon, that is, the probability of a positive marker in the population that
      will relapse (cases) and that will not relapse (controls). In the presence of
      censoring, sensitivity and specificity cannot be estimated by proportions because
      it is not known whether censored subjects should be considered as cases or
      controls. The solutions proposed do not enable to obtain asymptotic confidence
      intervals. We explore the use of inverse probability of censoring
      weighting/imputation (borrowed from the methodology used to correct for
      verification bias) to adjust the classification matrix for the presence of
      censoring. The adjustment based on weights estimated conditional on the marker
      turned to be equivalent to the adjustment based on imputation. These approaches,
      which address for the presence of marker-dependent censoring, showed a better
      performance than the adjustment based on weights estimated on the entire sample,
      even in the case of marker-independent censoring. We derived single intervals and
      confidence region for sensitivity and 1-specificity using the delta method. The
      confidence region is particularly useful for a binary marker because the marker
      has some ability to discriminate among cases and controls only if the region does
      not intersect the first quadrant bisector.

PMID- 22161770
TI  - Multi-angle ratiometric approach to measure chemical exchange in amide proton
      transfer imaging.
AB  - Amide proton transfer imaging, a specific form of chemical exchange saturation
      transfer imaging, has previously been applied to studies of acute ischemic
      acidosis, stroke, and cancer. However, interpreting the resulting contrast is
      complicated by its dependence on the exchange rate between amides and water, the
      amide concentration, amide and water relaxation, and macromolecular magnetization
      transfer. Hence, conventional chemical exchange saturation transfer contrast is
      not specific to changes such as reductions in pH due to tissue acidosis. In this
      article, a multi-angle ratiometric approach based on several pulsed-chemical
      exchange saturation transfer scans at different irradiation flip angles is
      proposed to specifically reflect exchange rates only. This separation of exchange
      effects in pulsed-chemical exchange saturation transfer experiments is based on
      isolating rotation vs. saturation contributions, and such methods form a new
      subclass of chemical exchange rotation transfer (CERT) experiments. Simulations
      and measurements of creatine/agar phantoms indicate that a newly proposed imaging
      metric isolates the effects of exchange rate changes, independent of other sample
      parameters.

PMID- 22161771
TI  - Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective
      as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR:
      A meta-analysis from six phase III randomized controlled trials.
AB  - Gefiinib and erlotinib are two similar small molecules of selective and
      reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR
      TKIs), which have been approved for second-line or third-line indication in
      previously treated advanced Non-small-cell lung cancer (NSCLC) patients. The
      results of comparing the EGFR-TKI with standard platinum-based doublet
      chemotherapy as the first-line treatment in advanced NSCLC patients with
      activated EGFR mutation were still controversial. A meta-analysis was performed
      to derive a more precise estimation of these regimens. Finally, six eligible
      trials involved 1,021 patients were identified. The patients receiving EGFR-TKI
      as front-line therapy had a significantly longer progression-free survival (PFS)
      than patients treated with chemotherapy [median PFS was 9.5 versus 5.9 months;
      hazard ratio (HR)=0.37; 95% confidence intervals (CI)=0.27-0.52; p<0.001]. The
      overall response rate (ORR) of EGFR-TKI was 66.60%, whereas the ORR of
      chemotherapy regimen was 30.62%, which was also a statistically significant favor
      for EGFR-TKI [relative risk (RR)=5.68; 95% CI=3.17-10.18; p<0.001]. The overall
      survival (OS) was numerically longer in the patients received EGFR-TKI than
      patients treated by chemotherapy, although the difference did not reach a
      statistical significance (median OS was 30.5 vs. 23.6 months; HR=0.94; 95%
      CI=0.77-1.15; p=0.57). Comparing with first-line chemotherapy, treatment of EGFR
      TKI achieved a statistical significantly longer PFS, higher ORR and numerically
      longer OS in the advanced NSCLC patients harboring activated EGFR mutations,
      thus, it should be the first choice in the previously untreated NSCLC patients
      with activated EGFR mutation.

PMID- 22161773
TI  - Risk factors for prediction of inadequate response to antiresorptives.
AB  - Some patients sustain fractures while on antiresorptives. Whether this represents
      an inadequate response (IR) to treatment or a chance event has not been
      elucidated. We performed a study to identify which patients are more likely to
      fracture while on treatment. This is a multicentric, cross-sectional study of
      postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals,
      classified as adequate responders (ARs) if on treatment with antiresorptives for
      5 years with no incident fractures or inadequate responders (IRs) if an incident
      fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary
      osteoporosis, and previous anti-osteoporosis treatment other than the assessed
      were exclusion criteria. Clinical, demographic, analytical, dual-energy X-ray
      absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTxTM)
      and structural/fractal analyses of distal radius were performed. A total of 179
      women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years)
      were included. History of prior fracture (p = 0.005), two or more falls in the
      previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p =
      0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p =
      0.004) were associated with IR. In the logistic regression models a fracture
      before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47-8.82;
      p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI,
      1.55-9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx
      fracture load (OR, 0.96; 95% CI, 0.93-0.99; p = 0.006; per every 100 units) was
      protective, although the latter became not significant when all three variables
      were fitted into the model. Therefore, we can infer that severity of the disease,
      with microarchitectural and structure deterioration, as shown by previous
      fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher
      risk of inadequate response to antiresorptives. More potent regimes should be
      developed and adequate supplementation implemented to solve this problem.

PMID- 22161772
TI  - Human cytomegalovirus infection and atherothrombosis.
AB  - Vascular endothelium, as a key regulator of hemostasis, mediates vascular
      dilatation, prevents platelet adhesion, and inhibits thrombin generation.
      Endothelial dysfunction caused by acute or chronic inflammation, such as in
      atherosclerosis, creates a proinflammatory environment which supports leukocyte
      transmigration toward inflammatory sites, and at the same time promotes
      coagulation, thrombin generation, and fibrin deposition in an attempt to close
      the wound. Life-long persistent infection with human cytomegalovirus (HCMV) has
      been associated with atherosclerosis. In vivo studies have revealed that HCMV
      infection of the vessel wall affects various cells including
      monocytes/macrophages, smooth muscle cells (SMCs) and endothelial cells (ECs).
      HCMV-infected SMCs within vascular lesions display enhanced proliferation and
      impaired apoptosis, which contribute to intima-media thickening, plaque formation
      and restenosis. Monocytes play a central role in the process of viral
      dissemination, whereas ECs may represent a viral reservoir, maintaining
      persistent infection in HCMV-infected atherosclerotic patients following the
      primary infection. Persistent infection leads to dysfunction of ECs and activates
      proinflammatory signaling involving nuclear factor kappaB, specificity protein 1,
      and phosphatidylinositol 3-kinase, as well as expression of platelet-derived
      growth factor receptor. Activation of these pathways promotes enhanced
      proliferation and migration of monocytes and SMCs into the intima of the vascular
      wall as well as lipid accumulation and expansion of the atherosclerotic lesion.
      Moreover, HCMV infection induces enhanced expression of endothelial adhesion
      molecules and modifies the proteolytic balance in monocytes and macrophages. As a
      consequence, infected endothelium recruits naive monocytes from the blood stream,
      and the concomitant interaction between infected ECs and monocytes enables virus
      transfer to migrating monocytes. Endothelial damage promotes thrombin generation
      linking inflammation and coagulation. HCMV, in turn, enhances the thrombin
      generation. The virus carries on its surface the molecular machinery necessary to
      initiate thrombin generation, and in addition, may interact with the
      prothrombinase protein complex thereby facilitating thrombin generation. Thus,
      infection of endothelium may significantly increase the production of thrombin.
      This might not only contribute to thrombosis in patients with atherosclerosis,
      but might also induce thrombin-dependent proinflammatory cell activation. This
      review summarizes the existing evidence on the role of HCMV in vascular
      inflammation.

PMID- 22161774
TI  - Heparin-coated colloidal mesoporous silica nanoparticles efficiently bind to
      antithrombin as an anticoagulant drug-delivery system.

PMID- 22161775
TI  - Epidermal growth factor receptor protein expression and genomic alterations in
      renal cell carcinoma.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) is involved in the
      progression of many cancer types and represents an important therapeutic target.
      METHODS: To determine the role of EGFR in renal cell carcinoma (RCC), the authors
      analyzed 1088 tumors in a tissue microarray format by using immunohistochemistry
      and fluorescence in situ hybridization (FISH). A subset of 63 cancers was
      sequenced for EGFR exon 18 through 21 mutations. RESULTS: EGFR expression was
      observed in 83.8% of clear cell carcinomas, in 68.2% of papillary carcinomas, in
      75% of chromophobe carcinomas, and in 50% of oncocytomas. Within clear cell
      carcinomas, the expression level of EGFR was associated with high tumor grade (P
      < .0001), advanced pathologic tumor classification (P < .0001), and, to a lesser
      extent, lymph node status (P = .0326). FISH analysis revealed increased EGFR copy
      numbers (high polysomy) in 5.5% of tumors and amplification in 0.1% of tumors.
      EGFR copy number increases were associated with EGFR protein expression (P =
      .0015). Within clear cell carcinomas, EGFR copy number increases were associated
      with high tumor grade (P < .0001), advanced pathologic tumor classification (P =
      .0472), and lymph node status (P = .0065). No exon 18 through 21 mutations were
      identified in 63 sequenced tumors. CONCLUSIONS: The authors concluded that
      increased EGFR expression occurs in a fraction of patients who have RCC with an
      unfavorable histologic phenotype. EGFR copy number gain represents 1 possible
      cause for EGFR overexpression; however, many over expressing tumors have a normal
      genotype. High polysomy (which is suggested to be predictive of a response to
      tyrosine kinase inhibitors) occurs in 5.6% of RCCs. Thus, the potential utility
      of anti-EGFR medications may be worth further investigation in a small but
      significant subset of patients with RCC.

PMID- 22161776
TI  - Hsp90 inhibitor 17-AAG inhibits progression of LuCaP35 xenograft prostate tumors
      to castration resistance.
AB  - BACKGROUND: Advanced prostate cancer is currently treated with androgen
      deprivation therapy (ADT). ADT initially results in tumor regression; however,
      all patients eventually relapse with castration-resistant prostate cancer. New
      approaches to delay the progression of prostate cancer to castration resistance
      are in desperate need. This study addresses whether targeting Heat shock protein
      90 (HSP90) regulation of androgen receptor (AR) can inhibit prostate cancer
      progression to castration resistance. METHODS: The HSP90 inhibitor 17-AAG was
      injected intraperitoneally into nude mice bearing LuCaP35 xenograft tumors to
      determine the effect of HSP90 inhibition on prostate cancer progression to
      castration resistance and host survival. RESULTS: Administration of 17-AAG
      maintained androgen-sensitivity, delayed the progression of LuCaP35 xenograft
      tumors to castration resistance, and prolonged the survival of host. In addition,
      17-AAG prevented nuclear localization of endogenous AR in LuCaP35 xenograft
      tumors in castrated nude mice. CONCLUSIONS: Targeting Hsp90 or the mechanism by
      which HSP90 regulates androgen-independent AR nuclear localization and activation
      may lead to new approaches to prevent and/or treat castration-resistant prostate
      cancer.

PMID- 22161777
TI  - Caregiving and positioning effects on preterm infant states over 24 hours in a
      neonatal unit in Taiwan.
AB  - In this prospective, descriptive study, we used a repeated-measures design to
      explore the 24-hour effects of caregiving and positioning on preterm infants'
      states and the factors associated with state changes. Thirty preterm infants
      (gestational age 27.6-36.1 weeks) were observed for 3 days in the neonatal
      intensive care unit to record six states: quiet sleep (QS), active sleep,
      transition, active awake, quiet awake, and fussy or crying. The occurrences of QS
      increased when infants received no caregiving, social interaction, non-nutritive
      sucking (NNS), and were laterally positioned. However, QS significantly decreased
      and fussy or crying state increased when infants received routine and intrusive
      caregiving. These results suggest that caregiving, NNS, and positioning should be
      appropriately provided to facilitate infants' sleep, and reduce fussiness or
      crying.

PMID- 22161778
TI  - Psychosocial and other working conditions: variation by employment arrangement in
      a sample of working Australians.
AB  - BACKGROUND: The evidence linking precarious employment with poor health is mixed.
      Self-reported occupational exposures in a population-based Australian sample were
      assessed to investigate the potential for differential exposure to psychosocial
      and other occupational hazards to contribute to such a relationship,
      hypothesizing that exposures are worse under more precarious employment
      arrangements (EA). METHODS: Various psychoscial and other working conditions were
      modeled in relation to eight empirically derived EA categories with Permanent
      Full-Time (PFT) as the reference category (N = 925), controlling for sex, age,
      and occupational skill level. RESULTS: More precarious EA were associated with
      higher odds of adverse exposures. Casual Full-Time workers had the worst exposure
      profile, showing the lowest job control, as well as the highest odds of multiple
      job holding, shift work, and exposure to four or more additional occupational
      hazards. Fixed-Term Contract workers stood out as the most likely to report job
      insecurity. Self-employed workers showed the highest job control, but also the
      highest odds of long working hours. CONCLUSIONS: Psychosocial and other working
      conditions were generally worse under more precarious EA, but patterns of adverse
      occupational exposures differ between groups of precariously employed workers.

PMID- 22161779
TI  - First century of Chagas' disease: an overview on novel approaches to nifurtimox
      and benzonidazole delivery systems.
AB  - Hundred years after the discovery of Chagas' disease, there is a lack of
      effective treatment to control this neglected disease caused by the parasite
      Trypanosoma cruzi. The transmission is primarily through vector-borne blood
      transfusion or during pregnancy, producing high mortality and morbidity among
      poor people in many countries of Latin America. In the last decades, the efforts
      have been focused mainly on the elimination of vectors. At the same time,
      screening of blood donors in order to avoid transfusional transmission has been
      improved all over the world. However, Chagas' disease is still a major public
      health problem, with estimates of nearly 90 million people at risk of infection
      and more than eight million infected in 18 endemic countries. Despite the high
      incidence in endemic regions and the dissemination of neglected diseases in North
      America and Europe, to date, there are only two drugs developed and prescribed
      for the treatment of Chagas' disease, nifurtimox (tablets of 120 mg) and
      benzonidazole (tablets of 100 mg). In this review, different approaches carried
      out in the last decades for developing novel pharmaceutical formulations for the
      delivery of nifurtimox and benznidazole are discussed.

PMID- 22161781
TI  - Modelling zwitterions in solution: 3-fluoro-gamma-aminobutyric acid (3F-GABA).
AB  - The conformations and relative stabilities of folded and extended 3-fluoro-gamma
      aminobutyric acid (3F-GABA) conformers were studied using explicit solvation
      models. Geometry optimisations in the gas phase with one or two explicit water
      molecules favour folded and neutral structures containing intramolecular NH...O-C
      hydrogen bonds. With three or five explicit water molecules zwitterionic minima
      are obtained, with folded structures being preferred over extended conformers.
      The stability of folded versus extended zwitterionic conformers increases on
      going from a PCM continuum solvation model to the microsolvated complexes, though
      extended structures become less disfavoured with the inclusion of more water
      molecules. Full explicit solvation was studied with a hybrid quantum
      mechanical/molecular-mechanical (QM/MM) scheme and molecular dynamics
      simulations, including more than 6000 TIP3P water molecules. According to free
      energies obtained from thermodynamic integration at the PM3/MM level and
      corrected for B3LYP/MM total energies, the fully extended conformer is more
      stable than folded ones by about -4.5 kJ mol(-1). B3LYP-computed (3)J(F,H) NMR
      spin-spin coupling constants, averaged over PM3/MM-MD trajectories, agree best
      with experiment for this fully extended form, in accordance with the original NMR
      analysis. The seeming discrepancy between static PCM calculations and experiment
      noted previously is now resolved. That the inexpensive semiempirical PM3 method
      performs so well for this archetypical zwitterion is encouraging for further
      QM/MM studies of biomolecular systems.

PMID- 22161782
TI  - Double-targeted and double-enhanced suicide gene therapy mediated by generation 5
      polyamidoamine dendrimers for prostate cancer.
AB  - Herpes simplex virus (HSV)-thymidine kinase (TK)/ganciclovir (GCV) system is one
      of the most widely used and efficient suicide gene therapy for prostate cancer,
      but the lack of favorable gene vector and target limits its application. In this
      study, we established a novel system using nonviral gene vector G5-PAMAM-D to
      express HSV-TK and connexin43 (Cx43) gene driven by prostate-specific membrane
      antigen (PSMA) promoter, and evaluated the anti-tumor effect of this system. G5
      PAMAM-D delivered PSMAe/p-TK-Cx43 showed expression of TK and Cx43 only in LNCaP
      cells, but not in PC-3 and other cells. The transfection efficiency of this
      system was comparable to lipofectamine 2000 by propidium iodide staining assay.
      With gemcitabine, folate-G5-PAMAM-D delivered PSMAe/p-TK-Cx43 (folate-G5-PAMAM
      D/PSMAe/p-TK-Cx43) significantly decreased prostate cancer LNCaP cell
      proliferation and promoted apoptosis in vitro. With gemcitabine, the systemic
      deliver of folate-G5-PAMAM-D/PSMAe/p-TK-Cx43 significantly inhibited tumor growth
      in the LNCaP xenograft animal model. Our study demonstrates that this double
      targeted and double-enhanced system is effective in inducing cell growth
      inhibition and apoptosis in vitro and suppressing tumor growth in vivo. In
      conclusion, Cx43 and gemcitabine combined with HSV-TK/GCV gene therapy using
      nonviral vector G5-PAMAM-D hold great potential as a novel approach for the gene
      therapy of prostate cancer.

PMID- 22161780
TI  - Protein loop closure using orientational restraints from NMR data.
AB  - Protein loops often play important roles in biological functions. Modeling loops
      accurately is crucial to determining the functional specificity of a protein.
      Despite the recent progress in loop prediction approaches, which led to a number
      of algorithms over the past decade, few rigorous algorithmic approaches exist to
      model protein loops using global orientational restraints, such as those obtained
      from residual dipolar coupling (RDC) data in solution nuclear magnetic resonance
      (NMR) spectroscopy. In this article, we present a novel, sparse data, RDC-based
      algorithm, which exploits the mathematical interplay between RDC-derived sphero
      conics and protein kinematics, and formulates the loop structure determination
      problem as a system of low-degree polynomial equations that can be solved
      exactly, in closed-form. The polynomial roots, which encode the candidate
      conformations, are searched systematically, using provable pruning strategies
      that triage the vast majority of conformations, to enumerate or prune all
      possible loop conformations consistent with the data; therefore, completeness is
      ensured. Results on experimental RDC datasets for four proteins, including human
      ubiquitin, FF2, DinI, and GB3, demonstrate that our algorithm can compute loops
      with higher accuracy, a three- to six-fold improvement in backbone RMSD, versus
      those obtained by traditional structure determination protocols on the same data.
      Excellent results were also obtained on synthetic RDC datasets for protein loops
      of length 4, 8, and 12 used in previous studies. These results suggest that our
      algorithm can be successfully applied to determine protein loop conformations,
      and hence, will be useful in high-resolution protein backbone structure
      determination, including loops, from sparse NMR data. Proteins 2012. (c) 2011
      Wiley Periodicals, Inc. 

PMID- 22161783
TI  - Association of MR relaxation and cartilage deformation in knee osteoarthritis.
AB  - We assessed the relationship between cartilage MR relaxation times and
      biomechanical response of tibiofemoral articular cartilage to physiological
      loading in healthy subjects and patients with osteoarthritis (OA). Female
      subjects above 40 years of age with (N(1)  = 20) and without (N(2)  = 10) OA were
      imaged on a 3T MR scanner using a custom made loading device. MR images were
      acquired with the knee flexed at 20 degrees  with and without a compressive load
      of 50% of the subject's bodyweight. The subjects were categorized based on the
      clinical MRI scoring of medial and lateral cartilage surfaces. Data were
      stratified twice into two equal groups (low and high) at the median value of
      T(1rho) and T(2) relaxation time. The change in contact area and cartilage
      deformation was measured within these groups. Paired Student's t-test (alpha =
      0.05) was used to analyze the effect of loading on contact area and deformation.
      The average area of the contact region in the medial compartment was
      significantly higher in OA subjects compared with normal subjects in both
      unloaded (314 +/- 112 mm(2) vs. 227 +/- 106 mm(2), p = 0.023) and loaded (425 +/-
      128 mm(2) vs. 316 +/- 107 mm(2), p = 0.01) conditions. The overall relative
      change of cartilage thickness in the medial compartment was significantly higher
      than the lateral compartment (-5.3 +/- 9.9% vs. -1.9 +/- 9.2%, p = 0.042). When
      cartilage was divided into deep and superficial layers, superficial layers showed
      higher changes in relaxation time (T(1rho) and T(2)) than the changes in
      relaxation time of whole cartilage (Normal: 12.5% vs. 6.9%; OA: 10.9% vs. 4.6%).
      The average T(1rho) and T(2) times, change in area of contact region, and change
      in cartilage thickness in subjects with OA were higher when compared to normal
      subjects. This study provides support for a relationship between the mechanical
      response of cartilage to physiological loading (cartilage-on-cartilage contact
      area and cartilage deformation) and MR relaxation times (T(1rho) and T(2)) in
      both OA patients and normal subjects.

PMID- 22161785
TI  - New insights into molecular mechanisms of sunitinib-associated side effects.
AB  - The introduction of targeted therapy represents a major advance in the treatment
      of tumor progression. Targeted agents are a novel therapeutic approach developed
      to disrupt different cellular signaling pathways. The tyrosine kinase inhibitor
      sunitinib specifically blocks multiple tyrosine kinase receptors that are
      involved in the progression of many tumors. Sunitinib is the current standard of
      care in first-line treatment of advanced renal cell carcinoma, and it is approved
      in imatinib-intolerant and imatinib-refractory gastrointestinal stromal tumors.
      However, it is increasingly evident that sunitinib may display collateral effects
      on other proteins beyond its main target receptors, eliciting undesirable and
      unexpected adverse events. A better understanding of the molecular mechanisms
      underlying these undesirable sunitinib-associated side effects will help
      physicians to maximize efficacy of sunitinib and minimize adverse events. Here,
      we focus on new insights into molecular mechanisms that may mediate sunitinib
      associated adverse events.

PMID- 22161787
TI  - Time to presenting to hospital and associated factors in stroke patients. A
      hospital-based study in Japan.
AB  - OBJECTIVE: To investigate multifaceted factors that constrain early stroke
      treatment, from both clinical and social standpoints. METHODS: This was a cross
      sectional study conducted at a general hospital in northern Japan. Data on time
      to presenting to hospital after stroke onset and its potential associated factors
      were retrospectively extracted from the medical records of hospitalised stroke
      patients and analysed. RESULTS: Median time of presenting to hospital after
      stroke onset for 287 patients was 12 hours (range, 0.4-347 hours), and 16.7% of
      cases presented within 2 hours of onset. Multivariate analysis revealed a
      significant level of association between a Japan Coma Scale score of >=1
      (OR=0.41; 95% CI, 0.20-0.86) and cardiogenic cerebral embolism (OR=0.36; 95% CI,
      0.15-0.85). The proportions of patients treated with recombinant tissue
      plasminogen activator, those with a Modified Rankin Scale score of >=2, and those
      in a rehabilitation hospital/long-term care ward or who died were significantly
      higher among patients who presented within 2 hours. CONCLUSION: Less than one
      fifth of our stroke patients presented to hospital within 2 hours. Although our
      results are preliminary given their limited generalisability and the
      retrospective nature of data collection, medical rather than social factors were
      found to be associated with time of presenting to hospital. Patients with severe
      symptoms presented to the hospital at an earlier stage after stroke onset. It is
      important to promote the earliest possible presentation to hospital after a
      stroke.

PMID- 22161788
TI  - Numerical simulation of SAR induced around Co-Cr-Mo hip prostheses in situ
      exposed to RF fields associated with 1.5 and 3 T MRI body coils.
AB  - When patients with metallic prosthetic implants undergo an MR procedure, the
      interaction between the RF field and the prosthetic device may lead to an
      increase in specific absorption rate (SAR) in tissues surrounding the prosthesis.
      In this work, the distribution of SAR(10g) around bilateral CoCrMo alloy hip
      prostheses in situ in anatomically realistic voxel models of an adult male and
      female due to RF fields from a generic birdcage coil driven at 64 or 128 MHz are
      predicted using a time-domain finite integration technique. Results indicate that
      the spatial distribution and maximum values of SAR(10g) are dependent on body
      model, frequency, and the position of the coil relative to the body. Enhancement
      of SAR(10g) close to the extremities of a prosthesis is predicted. Values of
      SAR(10g) close to the prostheses are compliant with recommended limits if the
      prostheses are located outside the coil. However, caution is required when the
      prostheses are within the coil since the predicted SAR(10g) close to an extremity
      of a prosthesis exceeds recommended limits when the whole body averaged SAR is 2
      W kg(-1) . Compliance with recommended limits is likely to require a reduction in
      the time averaged input power.

PMID- 22161789
TI  - [Innovation in the psychiatric business].

PMID- 22161790
TI  - [Stigmatisation of psychiatric patients by general practitioners and medical
      students: a review of the literature].
AB  - BACKGROUND: In clinical practice general practitioners (GPS) and society tend to
      stigmatise patients with psychiatric problems. AIM: To attempt to describe this
      stigmatisation by GPS and medical students on the basis of information given in
      the literature. METHOD: We searched the literature via PubMed using mesh terms:
      'family practice', 'physicians', 'family', 'mental disorder', 'attitude' and
      'psychiatry' and the word 'stigma'. In addition, literature was supplied by
      experts and articles were located by the snowball method. RESULTS: Stigmatisation
      constitutes a major obstacle in the psychiatric and somatic care that gps provide
      for patients with a psychiatric disorder. Although such patients have a higher
      somatic vulnerability as a result of their psychiatric problems, they receive
      fewer technical and exploratory investigations than other categories of patients.
      Medical students too have a negative attitude towards patients with a psychiatric
      disorder. More education and training could lead to less stigmatisation but the
      effect would probably be only temporary. Personal experience is the main factor
      that leads to greater empathy. CONCLUSION: The literature suggests that
      psychiatric patients are victims of self-inflicted stigmatisation and
      stigmatisation by society and doctors. This leads to social exclusion and poorer
      healthcare. By tackling the problem of stigmatisation we could greatly improve
      the quality of life and healthcare for this group of patients.

PMID- 22161791
TI  - [Seven views on mental disorder].
AB  - BACKGROUND: Anyone attempting to devise a system for classifying mental
      disorders, such as DSM-5, needs to know what is meant by a mental disorder. This
      matter is also highly relevant for doctors in their daily practice and for
      persons involved in scientific research. AIM: To present and discuss important
      views on the concept of mental disorder. METHOD: Recent relevant literature is
      discussed, the main emphasis being on philosophical studies of the concept of
      mental disorder. RESULTS: None of the views discussed provides a satisfactory
      answer to the question of how mental disorder should be defined and demarcated.
      Each view, however, does contain valuable points and elements that may help to
      offer a meaningful perspective on mental disorder. CONCLUSION: Mental disorder is
      a complex concept. The way in which it is defined and applied has far-reaching
      consequences. Psychiatry has a duty to define this concept as clearly and
      accurately as possible.

PMID- 22161792
TI  - [Creativity and psychiatric disorders: recent neuroscientific insights].
AB  - BACKGROUND: Creativity is an important human characteristic on which many of
      mankind's achievements are based. For centuries practitioners of various
      disciplines have deliberated over the possible connection between creativity and
      psychopathology. Even today the issue is still being investigated, mainly by
      groups working more or less independently; these range from art experts to
      psychiatrists and neuroscientists. AIM: In this article we bring together the
      foremost recent neuroscientific findings on the subject. METHOD: We searched for
      relevant articles via electronic databases using a broad-band search strategy and
      concentrating mainly on neuroscientific publications. RESULTS: Our study of
      relevant articles showed that both the definition and the measurability of
      creativity are still problematic. Psychometric and psychodiagnostic research
      supports a link between creativity and the psychopathology of bipolar,
      schizophrenic and especially schizotypal disorders; the results of imaging
      techniques are less consistent and genetic research reveals a link between
      creativity and proneness to psychosis. CONCLUSION: There seems to be a connection
      between creativity and psychopathology in the bipolar-schizophrenic continuum.
      This connection is even more evident within the individual components of
      creativity and symptom groups of these pathologies. There is a need for accurate
      definitions, measuring instruments and multidisciplinary collaboration.

PMID- 22161793
TI  - [Reorganisation of the mental health services in Belgium in 2011. Will this lead
      to better care for patients with a serious mental illness?].
AB  - BACKGROUND: In Article 107 of the hospital legislation the Belgian government
      provides for a possible reorganisation of current mental health care. According
      to the Article, hospital managers and the medical staff of residential care units
      in each region are permitted tot re-allocate resources in such a way that their
      current government allowance is used for the development of an alternative type
      of health care that is more community-based. AIM: To explore the possible
      consequences that such a step is likely to have on the current users of long-term
      residential care. METHOD: We looked critically at the draft text which was
      circulated in order tot explain the proposed reorganisation. We evaluated the
      scientific evidence concerning the feasibility of the ideas put forward in the
      text, focusing particularly on the care of patients with a serious mental
      illness. RESULTS: The method, which involves the re-allocation of funds in order
      to stimulate the reorganisation of care, is considered to be self-defeating. On
      the one hand, it constitutes a threat, leading to possible closure of the least
      profitable services, including hospital wards for long-stay patients. On the
      other hand, the proposed health care organisation poses a threat to the very
      group of patients who reside in such hospitals and it may in fact lower the level
      of care they receive. CONCLUSION: It will be necessary to check on the effects
      that this reorganisation will have on patients with a serious mental illness. We
      therefore propose some ways of monitoring the effects that the planned
      reorganisation is likely to have on this vulnerable group of patients.

PMID- 22161794
TI  - [Antigone: brother, sister and the tension in their relationship].
AB  - BACKGROUND: Although about 2500 years have passed since the first performances of
      Sophocles' tragedy Antigone, the play is nevertheless still able to move and
      inspire a wide audience. AIM: To demonstrate whether erotism and erotic elements
      underlie the conflict between the private domain and the public domain. METHOD:
      The relevant literature was studied and interpreted. RESULTS: Antigone can be
      read and interpreted in many different ways. The tragedy is often seen as a play
      about the position of women. In the most of the interpretations the central theme
      is seen as the conflict between loyalty to the state and loyalty to the family.
      In this essay it is argued that the conflict between the public domain and the
      private domain also occurs at an erotic level. Sexual feelings towards a brother
      make it difficult for a female sibling to make the move to a sexual partner
      outside the family. CONCLUSION: By focusing on the erotic conflict between
      brother and sister we can obtain a deeper understanding of the sexual
      relationship between siblings.

PMID- 22161795
TI  - [Jan Wier: a heretical physician for the witches: historical truth and myths].
AB  - BACKGROUND: Jan Wier was a remarkable person, well known to many as a leader of
      the fight against the persecution of witches. In a broader sense, he is regarded
      as one of the earlier defenders of human rights and as a acute observant of
      psychiatric disorders. AIM: To investigate whether these and other theories about
      Jan Wier are correct. METHOD: The biography studied was : "Jan Wier; a heretical
      physician for the witches" written by Vera Hoorens, professor of social and
      cultural psychology. RESULTS: Hoorens places the complete works by Wier in the
      historical context in which they were written. Wier was a particularly
      influential opponent of the persecution of witches, but this was not his main
      aim. His ideas were not original, although his books on witches show an early
      understanding of later psychiatric insight. Nevertheless he did contribute to an
      improvement in the administration of justice. His ideas on pathological anger
      were innovative, because when describing this disorder he included causes,
      effects, prognosis, treatment and prevention. CONCLUSION: On the basis of a
      thorough study of the complete works of Jan Wier, Hoorens distinguishes the
      historical truth from the myths that have arisen around this important person.

PMID- 22161796
TI  - [The Christmas prize puzzle in PPmP: the left side of his body caused him
      problems...]].

PMID- 22161797
TI  - [After the congress is before the congress].

PMID- 22161798
TI  - [Burden and need for psychosocial intervention of glioblastoma patients].
AB  - Glioblastoma patients should be provided with a professional health care system
      that helps reduce their psychosocial burden. The aim of this study was to
      identify patients in need of psychosocial intervention. In addition, it was
      examined whether physicians' assessments adequately address the burden patients
      are under and their need for intervention. During their visit to one of two
      neurosurgery outpatient departments, n = 49 glioblastoma patients filled out the
      short version of the Hornheider questionnaire (HFK). Consulting physicians also
      rated their patients' burdens in a specially adapted version of the questionnaire
      (HFK-F). The results of the psychometric evaluation with both instruments were
      satisfactory. The majority of the patients (76 %) were identified as in need of
      psychosocial intervention. All of them were correctly categorized with the
      physicians' ratings. Physicians overestimated some aspects of the patients'
      burden, particularly in regard to their problems with relaxing and fear of living
      with the illness. The patients' ratings concerning the quality of the information
      physicians provided and their overall state of health only corresponded with the
      physicians' ratings in roughly half of the cases.

PMID- 22161799
TI  - [The BMI: reputable risk index or cash machine?].

PMID- 22161800
TI  - [Psychotherapy of chronic depression with cognitive behavioral analysis system of
      psychotherapy (CBASP)].

PMID- 22161801
TI  - Association between systemic antipsoriatic drugs and cardiovascular risk in
      patients with psoriasis with or without psoriatic arthritis: a nationwide cohort
      study.
AB  - OBJECTIVE: Psoriasis is associated with ischemic heart disease (IHD). Results of
      prior studies have suggested that methotrexate (MTX) may improve vascular disease
      in patients with psoriasis and rheumatoid arthritis. The aim of this study was to
      assess the risk of new-onset IHDs in psoriasis patients, comparing those taking
      MTX with those taking other nonbiologic antipsoriatic drugs. METHODS: In this
      retrospective cohort study, we utilized claims data from the National Health
      Insurance Research Database of Taiwan to identify 179,200 subjects who had
      received a diagnosis of psoriasis, with or without psoriatic arthritis, on at
      least 3 visits. The risk of hospitalization for new-onset IHD was compared
      between psoriasis patients taking MTX monotherapy (n = 6,578; MTX case cohort)
      and psoriasis patients taking other nonbiologic antipsoriatic drugs (n = 5,471;
      reference control cohort) between January 1996 and December 2008. Additional
      adjustments were made for cardiovascular risk factors, number of hospital visits,
      Charlson comorbidity score, and use of other antiinflammatory drugs. RESULTS: The
      incidence rates of IHD were 666 cases per 100,000 person-years in the MTX case
      cohort and 830 cases per 100,000 person-years in the reference control cohort
      (unadjusted P = 0.027). Increasing age, male sex, presence of hypertension,
      presence of diabetes, Charlson comorbidity score, and use of phototherapies were
      independent risk factors for hospitalization related to a new IHD in the study
      cohorts. However, the multivariate-adjusted hazard ratio for IHD-related
      hospitalizations among patients receiving MTX, in comparison with those receiving
      other nonbiologic antipsoriatic drugs, was 0.97 (95% confidence interval 0.79
      1.19), after adjustment for age, sex, comorbidity score, number of hospital
      visits, and other antiinflammatory treatments for psoriasis. CONCLUSION: In
      patients with psoriasis with or without coexisting psoriatic arthritis, the
      adjusted risk of hospitalization for an IHD among individuals receiving MTX was
      comparable with that among individuals receiving other nonbiologic antipsoriatic
      drugs.

PMID- 22161802
TI  - Comparisons of multi b-value DWI signal analysis with pathological specimen of
      breast cancer.
AB  - Previous studies have reported that the signal attenuation of diffusion weighted
      magnetic resonance imaging for tumor tissues displays a non-monoexponential
      biexponential decay, and the apparent diffusion coefficients (ADCs) can be
      divided into a fast and slow diffusion component by using a simple biexponential
      decay model. The purpose of this study is to examine the non-monoexponential
      character of the diffusion weighted magnetic resonance imaging signal
      attenuations of breast cancers, estimate the fast and slow diffusion components,
      and compare them with the extra- and intracellular component information obtained
      from the pathological specimens. Twenty-two subjects having breast cancers
      underwent diffusion weighted magnetic resonance imaging using six b-values up to
      3500 s/mm(2) and the signal attenuations were analyzed using the biexponential
      function. The derived slow component fraction correlated with the cellular
      fraction and the ADCs converged to 0.2-0.3 * 10(-3) mm(2) /s for the higher
      cellular fractions. The ADCs of the fast component ranged from 1.3 to 3.9 * 10(
      3) mm(2) /s and showed no correlation with the extracellular components. This
      result suggests that the main reason for the decreasing ADC of a breast tumor is
      the decreasing fraction of the fast component and the increasing fraction of the
      slow component having a low ADC rather than the decreasing ADC of the fast
      component by the restricted water diffusion in the reduced extracellular spaces.

PMID- 22161804
TI  - Catalytic hydrogenation with frustrated Lewis pairs: selectivity achieved by size
      exclusion design of Lewis acids.
AB  - Catalytic hydrogenation that utilizes frustrated Lewis pair (FLP) catalysts is a
      subject of growing interest because such catalysts offer a unique opportunity for
      the development of transition-metal-free hydrogenations. The aim of our recent
      efforts is to further increase the functional-group tolerance and
      chemoselectivity of FLP catalysts by means of size-exclusion catalyst design.
      Given that hydrogen molecule is the smallest molecule, our modified Lewis acids
      feature a highly shielded boron center that still allows the cleavage of the
      hydrogen but avoids undesirable FLP reactivity by simple physical constraint. As
      a result, greater latitude in substrate scope can be achieved, as exemplified by
      the chemoselective reduction of alpha,beta-unsaturated imines, ketones, and
      quinolines. In addition to synthetic aspects, detailed NMR spectroscopic, DFT,
      and (2)H isotopic labeling studies were performed to gain further mechanistic
      insight into FLP hydrogenation.

PMID- 22161803
TI  - Parathyroid hormone treatment improves the cortical bone microstructure by
      improving the distribution of type I collagen in postmenopausal women with
      osteoporosis.
AB  - Although an important index, the level of bone mineral density (BMD) does not
      completely describe fracture risk. Another bone structural parameter, the
      orientation of type I collagen, is known to add to risk determination,
      independently of BMD, ex vivo. We investigated the Haversian system of transiliac
      crest biopsies from postmenopausal women before and after treatment with
      parathyroid hormone (PTH). We used the birefringent signal of circularly
      polarized light and its underlying collagen arrangements by confocal and electron
      microscopy, in conjunction with the degree of calcification by high-resolution
      micro-X-ray. We found that PTH treatment increased the Haversian system area by
      11.92 +/- 5.82 mm2 to 12.76 +/- 4.50 mm2 (p = 0.04); decreased bright
      birefringence from 0.45 +/- 0.02 to 0.40 +/- 0.01 (scale zero to one, p =
      0.0005); increased the average percent area of osteons with alternating
      birefringence from 48.15% +/- 10.27% to 66.33% +/- 7.73% (p = 0.034); and
      nonsignificantly decreased the average percent area of semihomogeneous
      birefringent osteons (8.36% +/- 10.63% versus 5.41% +/- 9.13%, p = 0.40) and of
      birefringent bright osteons (4.14% +/- 8.90% versus 2.08% +/- 3.36%, p = 0.10).
      Further, lamellar thickness significantly increased from 3.78 +/- 0.11 um to 4.47
      +/- 0.14 um (p = 0.0002) for bright lamellae, and from 3.32 +/- 0.12 um to 3.70
      +/- 0.12 um (p = 0.045) for extinct lamellae. This increased lamellar thickness
      altered the distribution of birefringence and therefore the distribution of
      collagen orientation in the tissue. With PTH treatment, a higher percent area of
      osteons at the initial degree of calcification was observed, relative to the
      intermediate-low degree of calcification (57.16% +/- 3.08% versus 32.90% +/-
      3.69%, p = 0.04), with percentage of alternating osteons at initial stages of
      calcification increasing from 19.75 +/- 1.22 to 80.13 +/- 6.47, p = 0.001. In
      conclusion, PTH treatment increases heterogeneity of collagen orientation, a
      starting point from which to study the reduction in fracture risk when PTH is
      used to treat osteoporosis.

PMID- 22161805
TI  - A framework for joint modeling and joint assessment of efficacy and safety
      endpoints for probability of success evaluation and optimal dose selection.
AB  - The evaluation of clinical proof of concept, optimal dose selection, and phase
      III probability of success has traditionally been conducted by a subjective and
      qualitative assessment of the efficacy and safety data. This, in part, was
      responsible for the numerous failed phase III programs in the past. The need to
      utilize more quantitative approaches to assess efficacy and safety profiles has
      never been greater. In this paper, we propose a framework that incorporates
      efficacy and safety data simultaneously for the joint evaluation of clinical
      proof of concept, optimal dose selection, and phase III probability of success.
      Simulation studies were conducted to evaluate the properties of our proposed
      methods. The proposed approach was applied to two real clinical studies. On the
      basis of the true outcome of the two clinical studies, the assessment based on
      our proposed approach suggested a reasonable path forward for both clinical
      programs.

PMID- 22161807
TI  - Quantitative analysis of lumbar intervertebral disc abnormalities at 3.0 Tesla:
      value of T(2)  texture features and geometric parameters.
AB  - T(2) relaxation time mapping provides information about the biochemical status of
      intervertebral discs. The present study aimed to determine whether texture
      features extracted from T(2) maps or geometric parameters are sensitive to the
      presence of abnormalities at the posterior aspect of lumbar intervertebral discs,
      i.e. bulging and herniation. Thirty-one patients (21 women and 10 men; age range
      18-51 years) with low back pain were enrolled. MRI of the lumbar spine at 3.0
      Tesla included morphological T(1) - and T(2) -weighted fast spin-echo sequences,
      and multi-echo spin-echo sequences that were used to construct T(2) maps. On
      morphological MRI, discs were visually graded into 'normal', 'bulging' or
      'herniation'. On T(2) maps, texture analysis (based on the co-occurrence matrix
      and wavelet transform) and geometry analysis of the discs were performed. The
      three T(2) texture features and geometric parameters best-suited for
      distinguishing between normal discs and discs with bulging or herniation were
      determined using Fisher coefficients. Statistical analysis comprised ANCOVA and
      post hoc t-tests. Eighty-two discs were classified as 'normal', 49 as 'bulging'
      and 20 showed 'herniation.' The T(2) texture features Entropy and Difference
      Variance, and all three pre-selected geometric parameters differed significantly
      between normal and bulging, normal and herniated, and bulging and herniated discs
      (p < 0.05). These findings suggest that T(2) texture features and geometric
      parameters are sensitive to the presence of abnormalities at the posterior aspect
      of lumbar intervertebral discs, and may thus be useful as quantitative biomarkers
      that predict disease.

PMID- 22161806
TI  - Race and prevalence of human papillomavirus infection among men residing in
      Brazil, Mexico and the United States.
AB  - Human papillomavirus (HPV) causes anal, penile and oropharyngeal cancers in men.
      Genital HPV prevalence in men appears to vary by world region with men residing
      in Asia having among the lowest prevalence. Unfortunately, there is little
      information on prevalence of HPV infection in men by race. The purpose of this
      study was to examine HPV prevalence by race across three countries. 3,909 men
      ages 18-70 years enrolled in an ongoing prospective cohort study of the natural
      history of HPV in men (The HIM Study) were included in the analysis. Participants
      completed risk factor questionnaires and samples were taken from the penile
      epithelium and scrotum for HPV detection. HPV testing of the combined DNA extract
      was conducted using PCR and genotyping. Asian/Pacific Islanders had the lowest
      HPV prevalence of 42.2% compared to Blacks (66.2%), and Whites (71.5%). The
      Asian/Pacific Islander race was strongly protective in univariate analysis
      (prevalence ratio (PR) = 0.59; 95% confidence interval (CI): 0.48-0.74) and
      multivariate analysis for any HPV infection (PR = 0.65; 95% CI: 0.52-0.8).
      Stratified analysis by lifetime number of female partners also showed strong
      inverse associations with the Asian/Pacific Islander race. We consistently
      observed the lowest prevalence of HPV infection among Asian/Pacific Islanders
      with moderate inverse associations even after various adjustments for potential
      confounding factors. Unmeasured behavioral factors, sexual mixing with low risk
      women, and/or race-specific differences in the frequency of germline variations
      among immune regulating genes may underlie these associations. Further studies
      among Asian populations that incorporate measures of immuno-genetics are needed
      to understand this phenomenon.

PMID- 22161808
TI  - Couple functioning and post-traumatic stress symptoms in US Army couples: the
      role of resilience.
AB  - The purpose of this study was to investigate combat-related post-traumatic stress
      symptoms (PTSS) and couple relationships in Army couples. US Army combat veteran
      couples (N = 66 couples) completed self-report questionnaires on couple
      functioning, coercion, resilience, and PTSS. In 23% of the couples (n = 15), both
      members had PTSS above the clinical cut-off for suspected Post-traumatic Stress
      Disorder (PTSD). Higher levels of PTSS were associated with lower couple
      functioning and resilience. Individuals with high resilience scores reported
      higher couple functioning scores, regardless of PTSS (p = .004). Future
      researchers should focus on the role of resilience in relation to couple
      functioning, and ways to amplify resilience in military couples.

PMID- 22161809
TI  - Staining of fluid-catalytic-cracking catalysts: localising Bronsted acidity
      within a single catalyst particle.
AB  - A time-resolved in situ micro-spectroscopic approach has been used to investigate
      the Bronsted acidic properties of fluid-catalytic-cracking (FCC) catalysts at the
      single particle level by applying the acid-catalysed styrene oligomerisation
      probe reaction. The reactivity of individual FCC components (zeolite, clay,
      alumina and silica) was monitored by UV/Vis micro-spectroscopy and showed that
      only clay and zeolites (Y and ZSM-5) contain Bronsted acid sites that are strong
      enough to catalyse the conversion of 4-fluorostyrene into carbocationic species.
      By applying the same approach to complete FCC catalyst particles, it has been
      found that the fingerprint of the zeolitic UV/Vis spectra is clearly
      recognisable. This almost exclusive zeolitic activity is confirmed by the fact
      that hardly any reactivity is observed for FCC particles that contain no zeolite.
      Confocal fluorescence microscopy images of FCC catalyst particles reveal
      inhomogeneously distributed micron-sized zeolite domains with a highly
      fluorescent signal upon reaction. By examining laboratory deactivated FCC
      catalyst particles in a statistical approach, a clear trend of decreasing
      fluorescence intensity, and thus Bronsted acidity, of the zeolite domains is
      observed with increasing severity of the deactivation method. By comparing the
      average fluorescence intensities obtained with two styrenes that differ in
      reactivity, it has been found that the Bronsted acid site strength within FCC
      catalyst particles containing ZSM-5 is more uniform than within those containing
      zeolite Y, as confirmed with temperature-programmed desorption of ammonia.

PMID- 22161810
TI  - Impact of recovery on fraction unbound using equilibrium dialysis.
AB  - Historically, recovery had been used to evaluate the data quality of plasma
      protein binding or tissue binding obtained from equilibrium dialysis assays. Low
      recovery was often indicative of high nonspecific binding, instability, or low
      solubility. This study showed that, when equilibrium was fully established in the
      dialysis assay, low recovery due to nonspecific binding had no impact on the
      determination of fraction unbound. The conclusion was supported by the principles
      of the equilibrium dialysis assay, experimental data, and mathematic simulations.
      The results suggested that the use of recovery as an acceptance criterion for the
      equilibrium dialysis assay in drug discovery was too restrictive, and introduced
      the additional burden of repeating studies unnecessarily.

PMID- 22161811
TI  - Rational design of ambipolar organic semiconductors: is core planarity central to
      ambipolarity in thiophene-naphthalene semiconductors?
AB  - Herein, we report a new family of naphthaleneamidinemonoimide-fused
      oligothiophene semiconductors designed for facile charge transport in organic
      field-effect transistors (OFETs). These molecules have planar skeletons that
      induce high degrees of crystallinity and hence good charge-transport properties.
      By modulating the length of the oligothiophene fragment, the majority carrier
      charge transport can be switched from n-type to ambipolar behavior. The highest
      FET performance is achieved for solution-processed films of 10-[(2,2'-bithiophen)
      5-yl]-2-octylbenzo[lmn]thieno[3',4':4,5]imidazo[2,1-b][3,8]phenanthroline
      1,3,6(2H)-trione (NDI-3 Tp), with optimized film mobilities of 2*10(-2) and
      0.7*10(-2) cm(2) V(-1) s(-1) for electrons and holes, respectively. Finally,
      these planar semiconductors are compared with their twisted-skeleton
      counterparts, which exhibit only n-type mobility, in order to understand the
      origin of the ambipolarity in this new series of molecular semiconductors.

PMID- 22161812
TI  - Lysophosphatidic acid receptor-3 increases tumorigenicity and aggressiveness of
      rat hepatoma RH7777 cells.
AB  - Lysophosphatidic acid (LPA), which interacts with G protein-coupled transmembrane
      LPA receptors exhibits several biological effects, such as cell proliferation,
      migration, and differentiation. Recently, it has been reported that alteration of
      LPA receptor genes occurs in several cancer cells. In this study, to assess the
      biological role of LPA receptor-3 (LPA3 ) in the pathogenesis of tumor cells, we
      generated the Lpar3-expressing cells (RHa3B12 and RHa3G8) from rat hepatoma
      RH7777 cells, and examined their abilities of cell migration and tumorigenicity,
      compared with the Lpar3-unexpressing cells. In cell motility and invasion assays,
      RHa3B12 and RHa3G8 cells showed significantly higher intrinsic activity without
      LPA treatment than control RH7777AB cells. LPA treatment further increased cell
      motility and invasion of these cells. The cell motility of RHa3B12 and RHa3G8
      cells stimulated by LPA treatment was significantly suppressed by pretreatment
      with inhibitors of Gi or Gq proteins. In a soft agar assay, the large sized
      colonies were formed in RHa3B12 and RHa3G8 cells, but not in RH7777AB cells. The
      cell survival of RHa3G8 cells treated with cisplatin (CDDP) or doxorubicin (DOX)
      was higher than that of RH7777AB cells, correlating with the elevated expression
      levels of multidrug-resistance related genes, Mdr1a, Mdr1b, and Gstp1. These
      results suggest that LPA3 may be involved in progression and aggressiveness of
      rat hepatoma RH7777 cells.

PMID- 22161813
TI  - The burden of occupational injury: a 1-year prospective study in Xuan Tien
      Commune, Viet Nam.
AB  - BACKGROUND: Developing nations carry a substantial portion of the global burden
      of injury, but without reliable injury surveillance, there is no way to
      characterize or prioritize the causes of work-related injury for prevention.
      METHODS: Injury data from 52 treatment sites in the Xuan Tien Commune, Vietnam
      with over 10,000 inhabitants were collected between January 1 and December 31,
      2006. Injured residents were interviewed to determine work-relatedness, relevant
      causes, disability, and burden. RESULTS: Five hundred four work-related injuries
      were reported from formal treatment sites (incidence rate of 87 per 1,000 FTE)
      with a mean lost work day of 11 days. Four thousand five hundred seventy-four
      lost work day equivalents were estimated based on actual days lost to recover
      plus work days lost earning income to pay for medical costs, accumulating a total
      direct burden to the community of 8,641 lost work day equivalents. Almost half of
      that burden was caused by work in manufacturing. First aid boxes placed in 40
      manufacturing enterprises yielded the 2nd highest reporting source. CONCLUSION:
      This study demonstrated the feasibility and value at the local level to build an
      active injury surveillance system which could have a large impact on preventing
      the burden of injuries in workplaces in Vietnam.

PMID- 22161814
TI  - Suppression assays with human T regulatory cells: a technical guide.
AB  - The suppression of inappropriate immune responses by Treg cells is one of the
      major ways that the body maintains immune tolerance and homeostasis. Since
      defects in the suppressive capacity of Treg cells underlie many different immune
      mediated diseases, there is great interest in developing ways to track the number
      and function of Treg cells as biomarkers of tolerance and in devising ways to
      enhance their function therapeutically. However, the methods of studying human
      Treg cells are fraught with technical challenges that can often lead to
      misinterpretation. The most common way to determine the suppressive capacity of
      human Treg cells is to measure their ability to suppress the proliferation of
      responding CD4(+)  T cells. Here, we discuss the technical considerations that
      must be taken into account when performing suppression of T-cell proliferation
      assays with human Treg cells. We also consider how T cells may falsely appear
      suppressive because of dying cells in the system, improper resting of T-cell
      lines prior to the assay, or insufficient proliferation of the responding T
      cells. We propose that, in the future, classification of a population of cells as
      "regulatory" should rely on more than a simple test for blockade of CD4(+)  T
      cell proliferation.

PMID- 22161815
TI  - The epigenetic promise for prostate cancer diagnosis.
AB  - BACKGROUND: Prostate cancer is the most common cancer diagnosis in men and a
      leading cause of death. Improvements in disease management would have a
      significant impact and could be facilitated by the development of biomarkers,
      whether for diagnostic, prognostic, or predictive purposes. The blood-based
      prostate biomarker PSA has been part of clinical practice for over two decades,
      although it is surrounded by controversy. While debates of usefulness are
      ongoing, alternatives should be explored. Particularly with recent
      recommendations against routine PSA-testing, the time is ripe to explore
      promising biomarkers to yield a more efficient and accurate screening for
      detection and management of prostate cancer. Epigenetic changes, more
      specifically DNA methylation, are amongst the most common alterations in human
      cancer. These changes are associated with transcriptional silencing of genes,
      leading to an altered cellular biology. METHODS: One gene in particular, GSTP1,
      has been widely studied in prostate cancer. Therefore a meta-analysis has been
      conducted to examine the role of this and other genes and the potential
      contribution to prostate cancer management and screening refinement. RESULTS:
      More than 30 independent, peer reviewed studies have reported a consistently high
      sensitivity and specificity of GSTP1 hypermethylation in prostatectomy or biopsy
      tissue. The meta-analysis combined and compared these results. CONCLUSIONS: GSTP1
      methylation detection can serve an important role in prostate cancer managment.
      The meta-analysis clearly confirmed a link between tissue DNA hypermethylation of
      this and other genes and prostate cancer. Detection of DNA methylation in genes,
      including GSTP1, could serve an important role in clinical practice.

PMID- 22161816
TI  - Kinetic and kinematic changes with the use of valgus knee brace and lateral wedge
      insoles in patients with medial knee osteoarthritis.
AB  - The effect of a valgus knee brace and a lateral wedged insole on knee and ankle
      kinematics and kinetics was evaluated in ten patients with medial knee
      osteoarthritis (OA). The knee orthosis was tested in two valgus adjustments (4
      degrees  and 8 degrees ), and the laterally wedged insole was fabricated with an
      inclination of 4 degrees . A motion capture system and force platforms were used
      for data collection and joint moments were calculated using inverse dynamics. The
      valgus moment applied by the orthosis was also measured using a strain gauge
      implemented in the orthosis' rotational axis. For the second peak knee adduction
      moment, decreases of 18%, 21%, and 7% were observed between baseline and test
      conditions for the orthosis in 4 degrees  valgus, in 8 degrees  valgus, and
      insole, respectively. Similar decreases were observed for knee lever arm in the
      frontal plane. Knee adduction angular impulse decreased 14%, 18%, and 7% from
      baseline to conditions for the orthosis in 4 degrees  valgus, in 8 degrees 
      valgus, and insole, respectively. Knee angle in the frontal plane reached a more
      valgus position during gait using the valgus knee brace. The valgus moment
      applied by the orthosis with 8 degrees  valgus adjustment was 30% higher than
      with 4 degrees  valgus adjustment. The valgus knee orthosis was more effective
      than the laterally wedged insole in reducing knee adduction moment in patients
      with medial knee OA.

PMID- 22161817
TI  - Free-breathing inner-volume black-blood imaging of the human heart using two
      dimensionally selective local excitation at 3 T.
AB  - Black-blood fast spin-echo imaging is a powerful technique for the evaluation of
      cardiac anatomy. To avoid fold-over artifacts, using a sufficiently large field
      of view in phase-encoding direction is mandatory. The related oversampling
      affects scanning time and respiratory chest motion artifacts are commonly
      observed. The excitation of a volume that exclusively includes the heart without
      its surrounding structures may help to improve scan efficiency and minimize
      motion artifacts. Therefore, and by building on previously reported inner-volume
      approach, the combination of a black-blood fast spin-echo sequence with a two
      dimensionally selective radiofrequency pulse is proposed for selective "local
      excitation" small field of view imaging of the heart. This local excitation
      technique has been developed, implemented, and tested in phantoms and in vivo.
      With this method, small field of view imaging of a user-specified region in the
      human thorax is feasible, scanning becomes more time efficient, motion artifacts
      can be minimized, and additional flexibility in the choice of imaging parameters
      can be exploited.

PMID- 22161818
TI  - Scalar coupling across [C-H...F-C] interactions in (sigma-aryl)-chelating post
      metallocenes.
AB  - The nature and importance of C-H...F-C interactions is a topical yet
      controversial issue, and the development of spectroscopic methods to probe such
      contacts is therefore warranted. A series of Group 4 bis(benzyl) complexes
      supported by (sigma-aryl)-2-phenolate-6-pyridyl [O,C,N-R(1)] ligands bearing a
      fluorinated R(1) group (CF(3) or F) in the vicinity of the metal has been
      prepared. The X-ray crystal structure of the CF(3)-substituted Hf derivative
      features intramolecular C-H...F-C and Hf...F-C contacts. All complexes have been
      characterized by multinuclear NMR spectroscopy. The (1)H and (13)C NMR spectra of
      [M(O,C,N-CF(3))(CH(2)Ph)(2)] derivatives display coupling (assigned to (1h)J(HF)
      and (2h)J(CF) for Ti; (3)J(HF) and (2)J(CF) (through M...F) for Hf and Zr)
      between the benzyl CH(2) and CF(3) moieties. [(1)H,(19)F]-HMBC NMR experiments
      have been performed for the M-[O,C,N-R(1)] complexes and their [O,N,C]
      counterparts, revealing significant scalar coupling across the C-H...F-C
      interactions for Ti-[O,C,N] and [O,N,C] species.

PMID- 22161819
TI  - Effect of oxidative stress on protein tyrosine phosphatase 1B in scleroderma
      dermal fibroblasts.
AB  - OBJECTIVE: Platelet-derived growth factor (PDGF) and its receptor, PDGFR, promote
      fibrosis in systemic sclerosis (SSc; scleroderma) dermal fibroblasts, and such
      cells in scleroderma skin lesions produce excessive reactive oxygen species
      (ROS). PDGFR is phosphorylated upon PDGF stimulation, and is dephosphorylated by
      protein tyrosine phosphatases (PTPs), including PTP1B. This study was undertaken
      to determine whether the thiol-sensitive PTP1B is affected by ROS in SSc dermal
      fibroblasts, thereby enhancing the phosphorylation of PDGFR and synthesis of type
      I collagen. This study also sought to investigate the effect of a thiol
      antioxidant, N-acetylcysteine (NAC), in SSc. METHODS: Fibroblasts were isolated
      from the skin of patients with diffuse SSc and normal healthy donors for cell
      culture experiments and immunofluorescence analyses. A phosphate release assay
      was used to determine the activity of PTP1B. RESULTS: Levels of ROS and type I
      collagen were significantly higher and amounts of free thiol were significantly
      lower in SSc fibroblasts compared to normal fibroblasts. After stimulation with
      PDGF, not only were PDGFR and ERK-1/2 phosphorylated to a greater extent, but
      also the ability to produce PTP1B was hampered in SSc fibroblasts. The activity
      of PTP1B was significantly inactivated in SSc fibroblasts as a result of cysteine
      oxidation by the raised levels of ROS, which was confirmed by the oxidation of
      multiple PTPs, including PTP1B, in SSc fibroblasts. Decreased expression of PTP1B
      in normal fibroblasts led to increased expression of type I collagen. Treatment
      of the cells with NAC restored the activity of PTP1B, improved the profile of
      PDGFR phosphorylation, decreased the numbers of tyrosine-phosphorylated proteins
      and levels of type I collagen, and scavenged ROS in SSc fibroblasts. CONCLUSION:
      This study describes a new mechanism by which ROS may promote a profibrotic
      phenotype in SSc fibroblasts through the oxidative inactivation of PTP1B, leading
      to pronounced activation of PDGFR. The study also presents a novel molecular
      mechanism by which NAC may act on ROS and PTP1B to provide therapeutic benefit in
      SSc.

PMID- 22161820
TI  - Financial incentives to improve organ donation: what is the opinion of the Vaud
      French-speaking population?
AB  - BACKGROUND: With the increase of the organ shortage, several authors assume that
      financial incentives would improve organ donation rates and fill the unbalance
      between the demand and the organs available for transplant medicine. This line of
      argument has been criticised with people arguing that an exchange of money for
      organs would violate the legal and the ethical principle of gratuity, decrease
      voluntarism and increase the body parts commodification phenomena. PURPOSE:
      Switzerland is often highlighted as having under-average organ donation rates
      compared to other European countries. In this paper we investigate the opinions
      of the Vaud French-speaking population concerning direct, indirect and non
      financial incentives in order to assess their opinions and anticipate the further
      debate. METHODS: As part of a broad survey about the organ donation decision
      making process, questions about incentives for both living and deceased organ
      donation were addressed to Vaud inhabitants and physicians. RESULTS: The data
      collected showed that respondents were opposed to rewarding both living and
      deceased organ donation. The analysis of positive answers showed that indirect
      and non financial incentives were the most likely choice to acknowledge the
      donor's act. People in critical financial situations preferred direct financial
      incentives. CONCLUSIONS: These results showed that altruism and gratuity were key
      values in the organ donation and transplantation social perceptions of the
      respondents. Thus, we assume that introducing financial incentives could tarnish
      the image of transplant medicine. Nevertheless, further studies are needed to
      evaluate if their introduction would improve the organ donation rates or decrease
      voluntarism.

PMID- 22161821
TI  - Preserving the allocation ratio at every allocation with biased coin
      randomization and minimization in studies with unequal allocation.
AB  - The demand for unequal allocation in clinical trials is growing. Most commonly,
      the unequal allocation is achieved through permuted block randomization. However,
      other allocation procedures might be required to better approximate the
      allocation ratio in small samples, reduce the selection bias in open-label
      studies, or balance on baseline covariates. When these allocation procedures are
      generalized to unequal allocation, special care is to be taken to preserve the
      allocation ratio at every allocation step. This paper offers a way to expand the
      biased coin randomization to unequal allocation that preserves the allocation
      ratio at every allocation. The suggested expansion works with biased coin
      randomization that balances only on treatment group totals and with covariate
      adaptive procedures that use a random biased coin element at every allocation.
      Balancing properties of the allocation ratio preserving biased coin randomization
      and minimization are described through simulations. It is demonstrated that these
      procedures are asymptotically protected against the shift in the rerandomization
      distribution identified for some examples of minimization with 1:2 allocation.
      The asymptotic shift in the rerandomization distribution of the difference in
      treatment means for an arbitrary unequal allocation procedure is explicitly
      derived in the paper.

PMID- 22161822
TI  - Spectroscopic response of ferrocene derivatives bearing a BODIPY moiety to water:
      a new dissociation reaction.
AB  - Ferrocence and its derivatives have long been known to be a class of stable
      organometallic compounds, and their dissociation usually occurs under harsh
      conditions. Here we report a new type of ferrocene derivatives, 4,4-difluoro-8
      ferrocenyl-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene and 4,4-difluoro-2,6
      diethyl-8-ferrocenyl-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene, which
      surprisingly can hydrolyze under mild conditions. These two derivatives,
      initially developed as donor-acceptor probes for reactive oxygen species by
      incorporating the electron donor of ferrocene as a quencher into the fluorophore
      of BODIPY (boron dipyrromethene difluoride), barely emit fluorescence. Upon
      reaction with H(2)O under the irradiation of natural light at room temperature,
      however, both of the probes display a dramatic color change and fluorescence
      retrievement. Detailed experimental results reveal that the reaction of the
      probes with H(2)O leads to the removal of a cyclopentadiene unit and iron(II),
      yielding a BODIPY derivative that retains the other cyclopentadiene unit and
      shows a large fluorescence enhancement (over 100-fold). Moreover, the increase in
      fluorescence intensity is directly proportional to microamount of water, and the
      presence of both light and H(2)O is indispensable in the reaction, which makes
      the present system of great potential not only for determining water but also for
      forming a AND logic gate. Most importantly, the present mild dissociation
      reaction may give a new insight into the stability of ferrocene and its
      derivatives.

PMID- 22161823
TI  - Developmental and cancer research on the mammary gland nowadays.
AB  - In this Special Issue, a number of common biological mechanisms are presented
      that govern both mammary gland development and mammary cancer. About half of the
      contributors present data on normal growth and differentiation of the gland,
      while for the others, cancer is the dominating theme. Yet, nearly all of them
      cross-refer to both research fields, and one of the innovating concepts in this
      respect is the existence of cellular ecosystems operating in development and
      cancer.

PMID- 22161824
TI  - Ecosystems of invasion and metastasis in mammary morphogenesis and cancer.
AB  - The present review describes molecular and cellular mechanisms of cancer invasion
      and metastasis as compared to mammary gland development considering communication
      inside and between ecosystems. At the level of the individual cell, invasion
      programs are written by an ecosystem of signalling pathways each of which steers
      several invasion-related cellular activities. At the supracellular level,
      communication within the epithelial compartment involves cells of the same
      origin, but with different phenotypes including stem cells.  A similar
      interaction occurs between the various cells of the stromal compartment. Crucial
      for our understanding of tumor or mammary gland ecosystems are the mutual
      interactions between cells of the epithelial and cells of the stromal
      compartment. An update is provided for endothelial cells, cancer-associated
      fibroblasts and macrophages that are implicated in angiogenesis, desmoplasia and
      inflammation respectively. At the level of the organism, distant ecosystems,
      comprising primary tumor site, sites of metastasis, bone marrow and endocrine
      glands among others, are in continuous contact through circulating cells and
      soluble ligands. Our review suggests consideration of these ecosystems when
      designing therapeutic strategies.

PMID- 22161825
TI  - The epidermal growth factor receptor/Erb-B/HER family in normal and malignant
      breast biology.
AB  - The EGFR/Erb-B receptor tyrosine kinases each play distinct and complementary
      roles in normal breast development. The four receptors form both homodimers and
      heterodimers in response to binding by ligands which show selectivity for one or
      more of the receptors (except Erb-B2). Together with the additional flexibility
      generated by the formation of different dimer pairs, these signalling networks
      play key roles in directing a variety of both autocrine and paracrine cellular
      responses. Complex two-way interactions between mammary epithelial cells and the
      surrounding stroma direct proliferation, duct formation, branching and terminal
      differentiation during puberty, pregnancy and lactation, with each receptor and
      ligand fulfilling distinct roles. Caricatures of the normal role of EGFR/Erb-B
      signalling resulting in aberrant cellular responses are seen in breast cancers,
      where over-expression and/or (less commonly) mutation of one or more of the
      receptors results in enhanced cell proliferation, motility, release of proteases
      and angiogenic factors. Given their importance in tumour progression, compared
      with most normal adult tissues and their links with resistance to chemotherapy
      and anti-endocrine therapy, Erb-B receptors (most notably Erb-B2) have been
      exploited as therapeutic targets. Monoclonal antibodies (e.g. trastuzumab,
      pertuzumab) and small molecule tyrosine kinase inhibitors (e.g. lapatinib,
      afatinib) have shown significant clinical responses in some breast cancer
      subtypes. Additional approaches include targeted toxins or drugs, peptide
      vaccines, immunRNase and chaperone inhibitors to deplete Erb-B2 protein levels.
      Greater understanding of the full spectrum of Erb-B-mediated signalling pathways
      and their misregulation in breast cancer will provide additional strategies to
      control malignant progression.

PMID- 22161826
TI  - From the laboratory to the patient and back--an interview with Marc Mareel.
      Interview by Marc E. Bracke.
AB  - The career of Marc Mareel is a synthesis of scientific research and clinical
      activity. During his medical studies, he already made his first enthusiastic
      steps in research via experimental work on avian developmental biology. Later,
      during his training as a radiotherapist, he founded his own laboratory for
      experimental cancer research. There he built up his international reputation as a
      pioneer in invasion research. Although invasion is the hallmark of tumor
      malignancy, he also kept an open mind about invasion in non-cancer conditions,
      such as in placental behavior, developmental biology, immunology and
      parasitology. His contribution to our understanding of invasion mechanisms has
      been both technical and conceptual. A number of assays have been developed in his
      lab, such as the embryonic chick heart and collagen gel invasion models, that
      have been (and still are) useful for many other research teams. He also
      contributed to the discovery of a number of key elements in the process of
      invasion, such as the stromal influence (including its extracellular matrix) and
      the cadherin family of cell-cell adhesion molecules. Concerning metastasis
      formation, he developed the original concept that a number of interacting eco
      systems are implicated, such as the primary tumor, regional lymph nodes, the bone
      marrow and the (pre)metastatic niches in distant organs. Since his retirement,
      Marc Mareel has continued to integrate clinical practice with research
      creativity. He favours the idea of translational research bringing the results of
      laboratory findings to medical applications, and exploiting the feedback to the
      laboratory. The team in the Laboratory of Experimental Cancer Research at Ghent
      University currently consists of about 25 collaborators, who continue to
      appreciate his inspiring ideas and suggestions.

PMID- 22161827
TI  - Four decades of discovery in breast cancer research and treatment--an interview
      with V. Craig Jordan. Interview by Marc Poirot.
AB  - V. Craig Jordan is a pioneer in the molecular pharmacology and therapeutics of
      breast cancer. As a teenager, he wanted to develop drugs to treat cancer, but at
      the time in the 1960s, this was unfashionable. Nevertheless, he saw an
      opportunity and through his mentors, trained himself to re-invent a failed
      "morning-after pill" to become tamoxifen, the gold standard for the treatment and
      prevention of breast cancer. It is estimated that at least a million women
      worldwide are alive today because of the clinical application of Jordan's
      laboratory research. Throughout his career, he has always looked at "the good,
      the bad and the ugly" of tamoxifen. He was the first to raise concerns about the
      possibility of tamoxifen increasing endometrial cancer. He described selective
      estrogen receptor modulation (SERM) and he was the first to describe both the
      bone protective effects and the breast chemopreventive effects of raloxifene.
      Raloxifene did not increase endometrial cancer and is now used to prevent breast
      cancer and osteoporosis.The scientific strategy he introduced of using long term
      therapy for treatment and prevention caused him to study acquired drug resistance
      to SERMs. He made the paradoxical discovery that physiological estrogen can be
      used to treat and to prevent breast cancer once exhaustive anti-hormone
      resistance develops. His philosophy for his four decades of discovery has been to
      use the conversation between the laboratory and the clinic to improve women's
      health.

PMID- 22161828
TI  - Signaling networks in cancer--an interview with Christian Gespach. Interview by
      Olivier De Wever.
AB  - The dynamic, innovative temperament of Christian Gespach is ideally suited to
      unraveling some aspects of the complex molecular networks connected with signal
      transduction, cancer progression and treatment. He is one of the pioneers who
      opened, in the early 1980s, new insights into the signaling mechanisms of G
      protein coupled receptor (GPCR) activation, desensitization, internalisation and
      crosstalks. Twenty five years later and in collaboration with Gespach, IPSEN
      pharmaceuticals designed pan-inhibitors of GPCR signaling, targeting Galpha
      subunits in breast cancer progression and other epithelial cancers. Creativity is
      of vital importance to understand signal transduction pathways engaged in cancer
      cell motility, invasion and drug resistance. Christian Gespach has published more
      than 200 papers in cancer research, a true signal transduction tale.

PMID- 22161829
TI  - Mammary gland stem cells: current status and future challenges.
AB  - Distinct subsets of cells, including cells with stem cell-like properties, have
      been proposed to exist in normal human breast epithelium and breast carcinomas.
      The cellular origins of epithelial cells contributing to gland development,
      tissue homeostasis and cancer are, however, still poorly understood. The mouse is
      a widely used model of mammary gland development, both directly by studying the
      mouse mammary epithelial cells themselves and indirectly, by studying
      development, morphogenesis, differentiation and carcinogenesis of
      xenotransplanted human breast epithelium in vivo.  While in early studies, human
      or mouse epithelium was implanted as fragments into the mouse gland, more recent
      technical progress has allowed the self-renewal capacity and differentiation
      potential of distinct cell populations or even individual cells to be
      interrogated. Here, we review and discuss similarities and differences between
      mouse and human gland development with particular emphasis on the identity and
      localization of stem cells, and the influence of the surrounding
      microenvironment. It is concluded that while recent advances in the field have
      contributed immense insight into how the normal mammary gland develops and is
      maintained, significant discrepancies exist between the mouse and human gland
      which should be taken into consideration in current and future models of mammary
      stem cell biology.

PMID- 22161830
TI  - c-Jun N-terminal kinase activity supports multiple phases of 3D-mammary
      epithelial acinus formation.
AB  - Primary murine mammary epithelial cells cultured on a laminin-rich-extracellular
      matrix (ECM) require c-Jun N-terminal kinase (JNK) activity for acinus formation.
      Inhibition of JNK (using SP600125) or small interfering RNA-mediated knockdown of
      JNK1 blocked acinus formation, impaired cell polarisation and lumen clearance and
      allowed sustained extracellular signal-regulated kinase (ERK) phosphorylation,
      cell proliferation, adhesion-independent cell survival and expression of
      epithelial-mesenchymal transition markers. ERK inhibition abolished the effects
      of JNK blockade. Interestingly, inhibition of JNK from the time of cell seeding
      blocked cell polarisation and lumen clearance; later inhibition (>= 6 h) only
      affected lumen clearance. ERK inhibition effectively protected cell polarisation
      but less so, lumen clearance. SP600125-treatment similarly affected acinus
      formation by the 'normal' human mammary epithelial MCF10A cell line. Expression
      of dominant-negative JNK1 in MCF10A cells also undermined acinus formation,
      generating large 'multi-acinar spheres' whose formation is probably driven by
      excessive luminal cell proliferation and cell survival. As JNK activity must be
      suppressed from the time of cell seeding to block cell polarisation, we studied
      the behaviour of MCF10A cells immediately after seeding in laminin rich matrix: 
      we detected engagement of cells with the matrix, early polarisation, movement of
      cells into clusters and 'epithelial-cell- like' behaviour of clustered cells.
      Inhibition of JNK activity or expression of dominant-negative JNK1 allowed cell
      engagement to the matrix, but blocked cell polarisation and all subsequent
      'behaviours'. While integrin activation occurred, tyrosine-phosphorylation of
      paxillin, Fak and Src was significantly damped by JNK inhibition. These results
      emphasise the multi-phase dependency of the organisation of mammary cells in 3D
      on JNK activity and suggest a 'permissive' support of ECM-integrin 'outside-in'
      signalling and a 'damping' of growth-factor ERK signalling as its two key cell
      physiological effects.

PMID- 22161831
TI  - Non-steroidal anti-inflammatory drugs target the pro-tumorigenic extracellular
      matrix of the postpartum mammary gland.
AB  - Breast cancer patients diagnosed postpartum have poor prognosis. The postpartum
      mammary gland undergoes tissue regression to return to the pre-pregnant state.
      This involution is characterized by wound healing programs known to be tumor
      promotional in other contexts. Previous studies have shown that mammary
      extracellular matrix (ECM) from nulliparous rats has tumor suppressive
      attributes, while mammary ECM from involuting mammary glands is promotional. In
      models of pregnancy-associated breast cancer, non-steroidal anti-inflammatory
      drug (NSAID) treatment targeted to postpartum involution inhibits tumor
      progression, in part by suppressing COX-2 dependent collagen deposition. Because
      mammary ECM proteins are coordinately regulated, NSAID treatment is anticipated
      to result in additional protective changes in the mammary extracellular matrix.
      Here, systemic NSAID treatment was utilized during postpartum involution to
      reduce mammary COX-2 activity. ECM was isolated from actively involuting glands
      of rats treated with NSAIDs and compared to ECM isolated from control-involution
      and nulliparous rats in 3D cell culture and xenograft assays. Compositional
      changes in ECM between groups were identified by proteomics. In four distinct 3D
      culture assays, normal and transformed mammary epithelial cells plated in NSAID
      involution ECM, phenocopied cells plated in ECM from nulliparous rats rather than
      ECM from control-involution rats. Tumor cells mixed with NSAID-involution ECM and
      injected orthotopically in mice formed smaller tumors than cells mixed with
      control-involution ECM. Proteomic analyses identified and 3D culture assays
      implicated the ECM protein tenascin-C as a potential mediator of tumor
      progression during involution that is decreased by NSAID treatment. In summary,
      NSAID treatment decreases tumor-promotional attributes of postpartum involution
      mammary ECM.

PMID- 22161832
TI  - Remodeling mechanisms of the mammary gland during involution.
AB  - The process of post-lactational regression, or involution, of the mammary gland
      is a complex event characterised by extensive death of the secretory epithelium
      coupled with remodelling of the extracellular matrix and adipogenesis to
      regenerate the fat pad. Associated with these events is an inflammatory cascade
      and acute phase response. The critical signalling pathways that regulated
      involution have been defined and a wide variety of genes have been shown to
      modulate the various processes involved, including cell death, phagocytosis,
      tissue remodelling and innate immune response.

PMID- 22161833
TI  - Connexins: a junctional crossroad to breast cancer.
AB  - The mammary gland presents a valuable model for developmental studies, spanning
      the embryonic stage through menarche to menopause. The dynamic remodeling of this
      gland is orchestrated by cellular heterogeneity, integrating mammogenic, systemic
      and local cues. Gap junctional intercellular communication provides pivotal cross
      talk of mammary epithelial cells with the surrounding cells and their local
      microenvironment. Connexins are involved in regulating normal and pathological
      mammary gland development, through channel-dependent and channel-independent
      roles. Modulation of the isoforms of connexins expressed, as well as their
      differential assembly into connexons and recruitment of a variety of associated
      partners, contributes to the complexity of signaling relayed at the membrane.
      This confers context-dependent functions of connexins at different stages of
      development and carcinogenesis. This review will summarize available knowledge
      about the functional dynamics of connexins and gap junctions in regulating normal
      mammary gland development and its pathophysiology.

PMID- 22161834
TI  - Insulin-like growth factor binding proteins and mammary gland development.
AB  - Mammary gland development is dependent upon insulin-like growth factors (IGFs) as
      survival factors. The actions of the IGFs are modulated by a family of IGF
      binding proteins (IGFBP1-6). Expression of the IGFBPs is both time-dependent and
      cell-specific during both the developmental phases and the involution of the
      mammary gland. Although studied extensively in vitro, understanding the roles of
      IGFBPs in vivo has been difficult, largely due to the fact that IGFBP knock-out
      mice have no dramatic phenotypes. This review examines the evidence from in vitro
      studies and the attempts to examine in vivo actions utilising models with IGFBP
      deficiency or over-expression. In vitro studies demonstrate that IGFBPs can act
      by inhibition of the survival effects of IGFs, as well as by enhancing the
      effects of IGFs. Because the IGFBPs are found associated with the extracellular
      matrix, a role for IGFBPs as a reservoir of IGFs or, alternatively as a potential
      barrier to IGFs, thereby restricting their entry into particular tissues or
      cellular compartments was postulated. We also provide evidence with respect to
      the IGF-independent actions of the IGFBPs which include receptors, nuclear
      localization, and interaction with the extracellular matrix and cell surface
      proteins including integrins. We believe that recent findings place some of the
      IGFBPs in a larger family of extracellular proteins, the secreted cysteine-rich
      protein (CCN) family, which have similar structural domains (involved in binding
      to IGFs, extracellular matrix and integrins) and are heavily implicated in tissue
      re-modeling and morphogenesis.

PMID- 22161835
TI  - Canine mammary tumors contain cancer stem-like cells and form spheroids with an
      embryonic stem cell signature.
AB  - We have investigated the presence of tentative stem-like cells in the canine
      mammary tumor cell line CMT-U229. This cell line is established from an atypical
      benign mixed mammary tumor, which has the property of forming duct-like
      structures in collagen gels. Stem cells in mammary glands are located in the
      epithelium; therefore we thought that the CMT-U229 cell line would be suitable
      for detection of tentative cancer stem-like cells. Side population (SP) analyses
      by flow cytometry were performed with cells that formed spheroids and with cells
      that did not. Flow cytometric, single sorted cells were expanded and re-cultured
      as spheroids. The spheroids were paraffin embedded and characterized by
      immunohistochemistry. SP analyses showed that spheroid forming cells (retenate)
      as well as single cells (filtrate) contained SP cells. Sca1 positive cells were
      single cell sorted and thereafter the SP population increased with repeated SP
      analyses. The SP cells were positively labeled with the cell surface-markers CD44
      and CD49f (integrin alpha6); however the expression of CD24 was low or negative.
      The spheroids expressed the transcription factor and stem cell marker Sox2, as
      well as Oct4. Interestingly, only peripheral cells of the spheroids and single
      cells were positive for Oct4 expression. SP cells are suggested to correspond to
      stem cells and in this study, we have enriched for tentative tumor stem-like
      cells derived from a canine mammary tumor. All the used markers indicate that the
      studied CMT-U229 cell line contains SP cells, which in particular have cancer
      stem-like cell characteristics.

PMID- 22161836
TI  - Proteome changes induced by overexpression of the p75 neurotrophin receptor
      (p75NTR) in breast cancer cells.
AB  - In breast cancer cells, the neurotrophin receptor p75(NTR) acts as a prosurvival
      factor able to stimulate resistance to apoptosis, but its mechanism of action
      remains incompletely defined. In this study, we investigated the global proteome
      modification induced by p75(NTR) overexpression in breast cancer cells treated by
      the pro-apoptotic agent tumor necrosis factor (TNF)-related-apoptosis-inducing
      ligand (TRAIL). p75(NTR) was stably overexpressed in the MCF-7 breast cancer
      cells and the impact of a treatment by TRAIL was investigated in wild type vs.
      p75(NTR) overexpressing cells. Proteins were separated in two-dimensional
      electrophoresis, and regulated spots were detected by computer assisted analysis
      before identification by MALDI-TOF/TOF mass spectrometry. In the absence of TRAIL
      treatment, p75(NTR) did not induce any change in the proteome of breast cancer
      cells. In contrast, after treatment with TRAIL, fragments of cytokeratin-8, -18
      and -19, as well as full length cytokeratin-18, were up-regulated by p75(NTR)
      overexpression. Of note, spectrin alpha-chain and the ribosomal protein RPLP0
      were induced by TRAIL, independently of p75(NTR) level. Interestingly, the well
      known stress-induced protein HSP-27 was less abundant when p75(NTR) was
      overexpressed, indicating that p75(NTR) overexpression reduced TRAIL induced cell
      stress. These data indicate that overexpression of p75(NTR) induces proteome
      modifications in breast cancer cells and provide information on how this receptor
      contributes in tumor cell resistance to apoptosis.

PMID- 22161837
TI  - P-cadherin role in normal breast development and cancer.
AB  - P-cadherin is a cell-cell adhesion molecule, whose expression is highly
      associated with undifferentiated cells in normal adult epithelial tissues, as
      well as with poorly differentiated carcinomas. Its expression has been already
      reported in human embryonic stem cells and it is presumed to be a marker of stem
      or progenitor cells of some epithelial tissues. In normal breast, P-cadherin has
      an essential role during ductal mammary branching, being expressed by the
      monolayer of epithelial cap cells at the end buds. In mature mammary tissue, its
      expression is restricted to the myoepithelium; it has been postulated that it may
      also be present in early luminal progenitor cells. In breast cancer, P-cadherin
      is frequently overexpressed in high-grade tumours, being a well-established
      indicator of poor patient prognosis. It has been reported as an important inducer
      of cancer cell migration and invasion, with underlying molecular mechanisms
      involving the signalling mediated by its juxtamembrane domain, the secretion of
      matrix metalloproteases to the extracellular media, and the cleavage of a P
      cadherin soluble form with pro-invasive activity. Intracellularly, this protein
      interferes with the endogenous cadherin/catenin complex, inducing p120-catenin
      delocalization to the cytoplasm, and the consequent activation of Rac1/Cdc42 and
      associated alterations in the actin cytoskeleton. Considering P-cadherin's role
      in cancer cell invasion and metastasis formation, a humanized monoclonal antibody
      was recently produced to antagonize P-cadherin-associated signalling pathways,
      which is currently under Phase I clinical trials. In this review, the most
      important findings about the role of P-cadherin in normal breast development and
      cancer will be illustrated and discussed, with emphasis on the most recent data.

PMID- 22161838
TI  - Sialylation regulates galectin-3/ligand interplay during mammary tumour
      progression--a case of targeted uncloaking.
AB  - Galectin-3 is involved both in facilitating detachment of cells from primary
      tumour sites and favouring cancer cell adhesion and survival to anoikis in the
      blood stream. The mechanisms behind these apparently contradictory roles of the
      lectin have not yet been resolved. In order to investigate possible interplays
      between galectin-3 and its ligands underlying their role in the metastatic
      process, we examined mucin-1 (MUC1) and epidermal growth factor receptor (EGFR),
      well-known galectin-3 ligands, as well as galectin-3-binding site expression in a
      series of spontaneous canine malignant mammary tumours (CMMT) and a metastatic
      CMMT cell line. Despite the fact that CMMT cells expressed MUC1 and EGFR
      homogeneously over their plasma membrane, intravascular tumour cells, positive
      for galectin-3, expressed MUC1 and EGFR in a more focal membrane localization.
      Moreover, MUC1 overexpression in primary CMMT was present in parallel with down
      regulation of galectin-3. Furthermore, in the CMT-U27 cell line, galectin-3 knock
      down led to increased MUC1 expression, while MUC1 knock-down led to down
      regulation of the lectin. Finally, removal of sialic acid from both CMMT and CMT
      U27 xenograft samples exposed galectin-3-ligands throughout the tumour tissue,
      whereas these ligands were only present in galectin-3-positive invading cells in
      untreated samples. Interestingly indeed, we show that in vessel-invading cells,
      there is interaction between galectin-3 and the T antigen in vivo. We therefore
      hypothesized that loss of galectin-3 and sialylation-related masking of its
      ligands, in conjunction with their overexpression in specific tumour cell
      subpopulations, are crucial in regulating adhesive/de-adhesive events in the
      progression and invasive capacity of metastatic cells.

PMID- 22161839
TI  - The role of non-muscle myosin IIA in aggregation and invasion of human MCF-7
      breast cancer cells.
AB  - Human MCF-7/6 breast cancer cells differ from their MCF-7/AZ counterparts by
      their invasiveness in a number of assays in vitro, such as invasion of MCF-7
      spheroids into embryonic chick heart fragments or type I collagen gels.
      Comparative proteomic analysis of these two variants revealed an identical
      pattern, except for a 230 kDa protein present in the invasive MCF-7/6 variant,
      but hardly detectable in the non-invasive MCF-7/AZ one. This protein appeared to
      be the non-muscle myosin IIA heavy chain (NMIIA), also coined MYH9. Experimental
      inhibition of NMIIA by reducing either its expression (via stable shRNA
      transduction) or its function (via the specific ATPase inhibitor blebbistatin)
      underpinned the decisive role of NMIIA in MCF-7 cell invasion. Inhibition of
      NMIIA indeed blocked the invasion of MCF-7/6 cells in three-dimensional invasion
      substrata such as embryonic chick heart fragments and type I collagen gels.
      Invasiveness of MCF-7/6 cells has been related to poor formation and compaction
      of aggregates, due to a functionally defective E-cadherin/catenin complex. Both
      genetic and pharmacological inhibition of NMIIA stimulated MCF-7/6 cell
      aggregation. Together, these data indicate that NMIIA is a decisive protein for
      MCF-7 cells to invade, indicating that this molecule is a candidate for targeted
      anti-invasive treatment.

PMID- 22161840
TI  - Role of cancer-associated fibroblasts in breast cancer development and prognosis.
AB  - Since Paget's "Seed and Soil" hypothesis in 1889 on cancer growth and metastasis,
      several studies on various solid tumors have confirmed the active role of the
      tumor milieu on the onset, growth and spread of neoplastic cells. Fibroblasts
      constitute the major components of the tumor microenvironment (stroma), and are
      therefore the most studied cell type. Therefore, a large amount of data has
      emerged showing the cancer-promoting function of these cells through paracrine
      effects that escort tumor cells through all the carcinogenesis steps. This
      involves many signaling proteins that transmit the message in both directions,
      allowing cooperative crosstalk between cancer cells and their stroma. This
      prompted several researchers to investigate the potential use of the molecular
      and cellular features of active stromal fibroblasts to generate specific tools
      for prevention, prognosis and treatment of cancer. Herein, I review the cellular
      and molecular features of active cancer-associated fibroblasts and their origin.
      Additionally, I summarize our current understanding of the procarcinogenic
      actions of these cells and their potential prognostic value for breast cancer
      patients.

PMID- 22161841
TI  - Tumor-associated macrophages in breast cancer: distinct subsets, distinct
      functions.
AB  - Macrophages display remarkable plasticity, allowing these cells to adapt to
      changing microenvironments and perform functions as diverse as tissue development
      and homeostasis, inflammation, pathogen clearance and wound healing. Macrophage
      activation can be triggered by Th1 cytokines and pathogen-associated or
      endogenous danger signals, leading to the formation of classically activated or
      M1 macrophages. On the other hand, anti-inflammatory mediators, including IL-4,
      IL-10, TGF-beta and M-CSF, induce diverse anti-inflammatory types of macrophages,
      known under the generic term M2. In human breast carcinomas, tumor-associated
      macrophage (TAM) density correlates with poor prognosis. In mouse models of
      breast cancer, eliminating macrophages from the tumor site, either via genetic or
      therapeutic means, results in retarded tumor progression. Over the years,
      multiple signals from the mammary tumor microenvironment have been reported to
      influence the TAM phenotype and TAM have been propagated as anti-inflammatory M2
      like cells. Recent developments point to the existence of at least two distinct
      TAM subpopulations in mammary tumors, based on a differential expression of
      markers such as CD206 or MHC II and different in vivo behaviour: perivascular,
      migratory TAM which are less M2-like, and sessile TAM found at tumor-stroma
      borders and/or hypoxic regions that resemble more M2-like or "trophic"
      macrophages. Hence, a further refinement of the molecular and functional
      heterogeneity of TAM is an avenue for further research, with a potential impact
      on the usefulness of these cells as therapeutic targets.

PMID- 22161842
TI  - Recent insights into the effect of natural and environmental estrogens on mammary
      development and carcinogenesis.
AB  - The present work reviews recent findings related to the action of steroidal
      (physiological) estrogens on normal mammary gland development and carcinogenesis,
      as well as effects of related environmental mediators (phyto- and xeno
      estrogens), the role of which remains controversial. Orchestration by estrogen
      receptors (i.e. ERalpha and ERbeta) and coregulators of growth, apoptosis and
      differentiation of epithelial cells, directed our analysis. The bidirectional
      coordination between epithelium and stroma in parallel with maintenance of
      stemness are also investigated. The relevance of nuclear and extranuclear
      localization of ERs and other eventual estrogen binding sites, mediating
      differential actions in regard to these various topics, is critically addressed
      to delineate the importance of direct and indirect activation procedures and
      delicate feedback loops (ligand-induced or/and cross-talk activation,
      respectively). The inclusion of the outlined regulatory concepts in drug design
      programs for the prevention and treatment of breast cancer may have potent
      effects.

PMID- 22161843
TI  - Exosome signaling in mammary gland development and cancer.
AB  - Exosomes are 40-100 nm intraluminal vesicles that are released by cells upon
      fusion of multivesicular endosomes (MVEs) with the plasma membrane. The Rab
      family of small GTPases, including Rab27A and Rab27B, control different steps of
      exosome release, including transport of MVEs and docking at the plasma membrane.
      Exosomes are long range message particles that mediate communication between
      cells in physiological conditions such as mammary gland development and
      lactation, but also in pathology such as breast cancer. Metastasis is the
      culmination of cancer progression and involves a complex interaction with the
      local and distant environment. Exosome messaging contributes to tumor environment
      interactions such as immune escape, thrombosis and myofibroblast differentiation,
      thereby modulating metastatic niche preparation.

PMID- 22161844
TI  - The tumor macroenvironment and systemic regulation of breast cancer progression.
AB  - Breast cancer is the most common malignancy among women worldwide and is the most
      common cause of death for women between 35 and 50 years of age. Women with breast
      cancer are at risk of developing metastases for their entire lifetime and,
      despite local and systemic therapies, approximately 30% of breast cancer patients
      will relapse (Jemal et al., 2010). Nearly all breast cancer related deaths are
      due to metastatic disease, even though metastasis is considered to be an
      inefficient process. In some cases, tumor cells disseminate from primary sites at
      an early stage, but remain indolent for protracted periods of time before
      becoming overt, life-threatening tumors. Little is known about the mechanisms
      that cause these indolent tumors to grow into malignant disease. Because of this
      gap in our understanding, we are unable to predict which breast cancer patients
      are likely to experience disease relapse or develop metastases years after
      treatment of their primary tumor. A better understanding of the mechanisms and
      signals involved in the exit of tumor cells from dormancy would not only allow
      for more accurate selection of patients that would benefit from systemic therapy,
      but could also lead to the development of more targeted therapies to inhibit the
      signals that promote disease progression. In this review, we address the
      systemic, or "macroenvironmental", contribution to tumor initiation and
      progression and what is known about how a pro-tumorigenic systemic environment is
      established.

PMID- 22161845
TI  - Perampanel, an AMPA antagonist, found to have no benefit in reducing "off" time
      in Parkinson's disease.
AB  - BACKGROUND: Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5
      methyl-4-isoxazole-propionic acid receptor antagonist. Two multicenter
      randomized, double-blind, placebo-controlled, parallel-group phase III studies
      assessed the efficacy and safety of adjunctive perampanel in patients with
      Parkinson's disease and motor fluctuations. METHODS: In both phase III studies
      (301 and 302), levodopa-treated patients were randomized and treated with once
      daily oral placebo (n = 504), perampanel 2 mg (n = 509), or perampanel 4 mg (n =
      501). The primary end point was change in daily "off" time from baseline. The
      treatment period was 30 weeks in study 301 and 20 weeks in study 302. RESULTS:
      For any efficacy end point, perampanel 2 or 4 mg was not superior to placebo.
      Perampanel was well tolerated up to 4 mg/day. CONCLUSIONS: Perampanel failed to
      significantly improve motor symptoms versus placebo. There was also no effect on
      the duration or disability of levodopa-induced dyskinesia.

PMID- 22161846
TI  - From the observation DAC: romidepsin revisited.

PMID- 22161847
TI  - ITP: tolerance lost.

PMID- 22161848
TI  - Innovation in myeloma treatments PARP excellence!

PMID- 22161849
TI  - Getting to know JAK.

PMID- 22161850
TI  - It dices, it splices!

PMID- 22161851
TI  - Effect of combined dexamethasone/lenalidomide therapy on NK cell-receptor levels
      in myeloma patients.

PMID- 22161852
TI  - Homologous recombination of wild-type JAK2, a novel early step in the development
      of myeloproliferative neoplasm.

PMID- 22161853
TI  - Differential expression of MMP-2 and MMP-9 activity in megakaryocytes and
      platelets.

PMID- 22161854
TI  - Some observations on the geometry of megakaryocyte mitotic figures: Buckyballs in
      the bone marrow.

PMID- 22161855
TI  - [Physicians' resilience--salutogenetic practices and attitudes of experienced
      physicians].
AB  - What enables physicians to cope efficiently with their every day stressors? Which
      strategies and attitudes contribute to long term job satisfaction and
      biopsychosocial health throughout their career? In order to work out the
      resiliency processes and coping strategies of residents and senior physicians we
      conducted 200 qualtitative expert interviews. The analysis revealed 30 main
      categories, referring to 5 subsystems: relating to patients and colleagues,
      dealing with structural restrictions, maintaining private relations and fields of
      interests and developing self-awareness. Based on the empirical salutogenetic
      practices and attitudes we draw conclusions for prevention.

PMID- 22161856
TI  - [Psychometric analysis of the Turkish speaking version of the "Hamburg Modules
      for the Assessment of Psychosocial Health" (T-HEALTH-49)].
AB  - Based on the German original questionnaire of the "Hamburger modules for
      measuring generic aspects of psycho-social health in the therapeutic practice"
      (HEALTH-49) a Turkish speaking version (T-HEALTH-49) was cross-cultural
      sensitively developed. The psychometric properties have been analysed by means of
      a clinical sample of Turkish speaking patients (N=311). The questionnaire proves
      to be practical, the dimensional structure and the relatively independence of the
      modules have been confirmed by factor analysis. The single scales are
      characterised by satisfactory to high reliability and satisfactory validity. The
      T-HEALTH-49 considers adequately psychosocial aspects in diagnostic, therapy
      planning and quality assurance. The questionnaire can be downloaded for free
      (www.hamburger-module.de).

PMID- 22161857
TI  - [Steroid use in free time bodybuilders].
AB  - A sample of 74 male bodybuilders was analyzed for relationships between steroid
      abuse (abuse n=31; no abuse n=43) and self-esteem (Multidimensionale
      Selbstwertskala MSWS), body-image (Body-Image Questionnaire FK-ASA) as well as
      teasing (Physical Appearance Related Teasing Scale PARTS). In a logistic
      regression analysis age (p=0.001), low values for body expression (p=0.036) and
      high self-esteem (p=0.024) predicted steroid intake; training frequency or
      teasing experiences showed no effect. Contrary to earlier findings high and not
      low self-esteem was associated with steroid abuse. Because of the overlap between
      constructs narcissism and self-esteem further studies should disentangle the role
      of narcissism and self-esteem for steroid abuse in bodybuilders.

PMID- 22161858
TI  - Assessing mitochondrial respiration in isolated hearts using (17)O MRS.
AB  - The application of (17)O MRI and MRS for the evaluation of cardiac mitochondrial
      function has been limited because of the challenge of detecting metabolic
      H(2)(17)O in the vast background of naturally abundant H(2)(17)O. In this study,
      we have developed a direct (17)O MRS approach to examine the feasibility and
      sensitivity of detecting metabolically produced H(2)(17)O in isolated rat hearts
      perfused with (17)O(2)-enriched Krebs-Henseleit buffer containing normal (1.5 mm)
      and high (2.5 mm) calcium (Ca(2+)) concentrations to induce high workload.
      Consistent with increased workload at high Ca(2+) concentration, the measured
      myocardial oxygen consumption rate (MVO(2)) increased by 82%. Dynamic (17)O MRS
      showed an accelerated increase in the H(2)(17)O signal at high Ca(2+)
      concentration, suggesting increased mitochondrial production of H(2)(17)O in
      concordance with the increased workload. A compartment model was developed to
      describe the kinetics of H(2)(17)O production as a function of MVO(2). The
      myocardial (17)O(2) consumption rate (MV(17)O(2) was determined by least-squares
      fitting of the model to the NMR-measured H(2)(17)O concentration. Consistent with
      the measured MVO(2), the model-determined MV(17)O(2) showed a 92% increase at
      high Ca(2+) concentration. The increase in metabolic activity at high workload
      allowed the balance between ATP production and utilization to be maintained,
      leading to a similar phosphocreatine to ATP ratio. These results demonstrate that
      dynamic (17)O MRS can provide a valuable tool for the detection of an altered
      metabolic rate associated with a change in cardiac workload.

PMID- 22161859
TI  - Role of excipients on solid-state properties of piroxicam during processing.
AB  - There is a need for an improved process understanding of solid dosage
      pharmaceuticals. In the present study, Raman spectroscopy together with partial
      least squares (PLS) regression was used to monitor the solid-state composition of
      piroxicam during processing in the presence of excipients. It was found that
      including variable selection in PLS regression offers improved quantitative
      models in terms of predictive performance, easier interpretation of results and
      reduced experimental workload relative to full-spectrum PLS regression. By means
      of the applied interval PLS (iPLS) regression model, it was observed that
      excipients with high water-absorbing potential (microcrystalline cellulose and
      hydroxypropyl cellulose) and a water-activity-reducing solvent (ethanol) delayed
      the onset of monohydrate formation during processing in aqueous environments. An
      alkalizing excipient (sodium bicarbonate) decreased the onset time of monohydrate
      formation during wet granulation and decreased the dehydration rate during a
      drying operation. In this study it is demonstrated that the physical stability of
      hydrate-anhydrate systems in process environments is complicated by a multitude
      of factors on both macroscopic level and molecular level, and that variable
      selection for PLS regression is a valuable tool for screening the effects of
      excipients on the solid-state properties of pharmaceuticals.

PMID- 22161860
TI  - Overexpression of Evi-1 oncoprotein represses TGF-beta signaling in colorectal
      cancer.
AB  - Human colorectal cancer (CRC) cells are resistant to the anti-proliferative
      effect of transforming growth factor-beta (TGF-beta), suggesting that disruption
      of TGF-beta signaling plays an important role in colorectal carcinogenesis.
      Ecotropic virus integration site-1 (Evi-1) oncoprotein represses TGF-beta
      signaling by interacting with Smads, but its role in CRC has not been
      established. The purpose of this study is to determine whether Evi-1 plays
      role(s) in CRCs and to characterize Evi-1 transcript(s) in CRCs. Evi-1 was
      overexpressed in 53% of human CRC samples, 100% of colon adenoma samples, and
      100% of human colon cancer cell lines tested. Using 5' RACE, we cloned a novel
      Evi-1 transcript (Evi-1e) from a human CRC tissue and found that this novel
      transcript was expressed at a higher level in CRC tissues than in normal tissues
      and was the major Evi-1 transcript in CRCs. Transient Evi-1 transfection
      inhibited TGF-beta-induced transcriptional activity and reversed the growth
      inhibitory effect of TGF-beta in MC-26 mouse colon cancer cells. In conclusion,
      we have identified overexpression of Evi-1 oncoprotein as a novel mechanism by
      which a subset of human CRCs may escape TGF-beta regulation. We have also
      identified a novel Evi-1 transcript, Evi-1e, as the major Evi-1 transcript
      expressed in human CRCs.

PMID- 22161861
TI  - Epithelial-mesenchymal transition predicts sensitivity to the dual IGF-1R/IR
      inhibitor OSI-906 in hepatocellular carcinoma cell lines.
AB  - A growing body of data indicates that inhibiting the type 1 insulin-like growth
      factor receptor (IGF-1R) might be an effective treatment strategy for
      hepatocellular carcinoma (HCC). OSI-906 is a dual IGF-1R/IR kinase inhibitor
      currently in phase II clinical development for HCC. However, biomarkers are
      lacking to help identify patients with HCC who are more likely to benefit from
      OSI-906 treatment. We sought to determine the effect of OSI-906 on proliferation
      against a panel of 21 HCC cell lines and to investigate molecular determinants of
      responsiveness to OSI-906. We identified a subset of HCC cell lines that was
      sensitive to OSI-906, and sensitivity is associated with elevated phosphorylation
      levels of IGF-1R and IR and greater inhibition of AKT signaling. Dual targeting
      of both receptors seems to be important for maximal inhibition as treatment with
      a selective IGF-1R-neutralizing antibody was associated with increased IR
      signaling, whereas OSI-906 fully inhibited both phosphorylated IR and IGF-1R and
      resulted in greater inhibition of the IRS/AKT pathway. Epithelial-mesenchymal
      transition (EMT) seems to predict HCC cell sensitivity to OSI-906, as the
      epithelial phenotype is strongly associated with expression of IGF-2 and IR,
      activation of IGF-1R and IR, and sensitivity to OSI-906, alone or in combination
      with erlotinib. Induction of EMT upon treatment with TGFbeta reduced sensitivity
      to OSI-906. Collectively, these data support the concept for dual IGF-1R/IR
      targeting in HCC, where EMT status and expressions of IGF-2 and IR may be used to
      identify those patients who are most likely to benefit from treatment with an IGF
      1R/IR dual inhibitor.

PMID- 22161862
TI  - Biphenyl-based diaminophosphine oxides as air-stable preligands for the nickel
      catalyzed Kumada-Tamao-Corriu coupling of deactivated aryl chlorides, fluorides,
      and tosylates.

PMID- 22161863
TI  - Kinetic consequences of native state optimization of surface-exposed
      electrostatic interactions in the Fyn SH3 domain.
AB  - Optimization of surface exposed charge-charge interactions in the native state
      has emerged as an effective means to enhance protein stability; but the effect of
      electrostatic interactions on the kinetics of protein folding is not well
      understood. To investigate the kinetic consequences of surface charge
      optimization, we characterized the folding kinetics of a Fyn SH3 domain variant
      containing five amino acid substitutions that was computationally designed to
      optimize surface charge-charge interactions. Our results demonstrate that this
      optimized Fyn SH3 domain is stabilized primarily through an eight-fold
      acceleration in the folding rate. Analyses of the constituent single amino acid
      substitutions indicate that the effects of optimization of charge-charge
      interactions on folding rate are additive. This is in contrast to the trend seen
      in folded state stability, and suggests that electrostatic interactions are less
      specific in the transition state compared to the folded state. Simulations of the
      transition state using a coarse-grained chain model show that native
      electrostatic contacts are weakly formed, thereby making the transition state
      conducive to nonspecific, or even nonnative, electrostatic interactions. Because
      folding from the unfolded state to the folding transition state for small
      proteins is accompanied by an increase in charge density, nonspecific
      electrostatic interactions, that is, generic charge density effects can have a
      significant contribution to the kinetics of protein folding. Thus, the
      interpretation of the effects of amino acid substitutions at surface charged
      positions may be complicated and consideration of only native-state interactions
      may fail to provide an adequate picture.

PMID- 22161864
TI  - Comparison of vascular remodeling in patients treated with sirolimus-versus
      zotarolimus-eluting stent following acute myocardial infarction.
AB  - BACKGROUND: The differences in the vascular response to stent implantation or in
      the incidence of late acquired stent malapposition among different types of drug
      eluting stents are not well known in patients with acute myocardial infarction
      (MI). HYPOTHESIS: The pattern of vascular remodeling and degree of neointimal
      proliferation were different depending on the different types of drug-eluting
      stents. METHODS: This study used intravascular ultrasound (IVUS) to investigate
      vascular remodeling in patients treated with implantation of sirolimus-eluting
      stents (SESs) vs zotarolimus-eluting stents (ZESs) following acute MI. The study
      population consisted of 100 patients with acute MI who were treated either with
      SES (n = 41) or ZES (n = 59) and underwent both poststenting and 9-month follow
      up IVUS examination. Serial vascular changes surrounding stented segments were
      compared between SES- and ZES-treated lesions. RESULTS: Percentage of neointimal
      volume obstruction at follow-up was significantly smaller in SES-treated compared
      to ZES-treated lesions (2.8 +/- 7.1% vs 18.1 +/- 15.7%, respectively; P < 0.001).
      However, positive vascular remodeling, which was defined as greater than 10%
      increase in external elastic membrane volume index (31.7% vs 10.2%, respectively,
      P = 0.007), and late acquired stent malapposition (12.0% vs 0%, respectively, P =
      0.006 ) occurred more frequently in SES-treated than in ZES-treated lesions.
      CONCLUSIONS: The pattern of vascular remodeling, including positive remodeling,
      late acquired stent malapposition, and degree of neointimal proliferation might
      be different depending on the different types of drug-eluting stents in patients
      with acute MI.

PMID- 22161865
TI  - MiR-146a suppresses tumor growth and progression by targeting EGFR pathway and in
      a p-ERK-dependent manner in castration-resistant prostate cancer.
AB  - BACKGROUND: Castration-resistant prostate cancer (CRPC) is a leading cause of
      cancer-related deaths in elder men. This disease has limited therapeutic options
      and poor prognosis as the underlying molecular mechanisms are not clearly
      understood. Given the emerging roles of microRNA (miRNA) as a key regulator, we
      postulated that miRNA may play a significant role in CRPC formation. METHODS: miR
      146a levels in 15 androgen-dependent prostate cancer (ADPC) tissues and 5 CRPC
      tissues were measured by qRT-PCR. Effects of miR-146a in cell proliferation and
      migration in vitro and in vivo were evaluated by MTT assay, colony formation
      assay, transwell migratory assay, and tumor formation assay, respectively.
      RESULTS: we found that miR-146a expression was significantly decreased in CRPC
      tissues compared to ADPC tissues. Functional analyses showed that ectopic
      overexpression of miR-146a in androgen-independent cell lines not only inhibited
      cell growth, colony formation, and migration in vitro, but also reduced
      tumorigenicity and angiogenesis in vivo. Mechanistic studies revealed that miR
      146a repressed the expression of EGFR through binding to its 3'-untranslated
      region. Also, miR-146a inhibited the expression of MMP2, one of the most
      important genes in tumor progression. Moreover, downregulation of p-ERK
      expression significantly abrogated miR-146a-induced prostate cancer cell
      proliferation. CONCLUSIONS: Our findings suggest that ubiquitous loss of miR-146a
      is a critical mechanism for overexpression of EGFR in CRPC, which is crucial to
      better understanding the pathogenesis of CRPC.

PMID- 22161866
TI  - R*(2) mapping in the presence of macroscopic B0 field variations.
AB  - R2 mapping has important applications in MRI, including functional imaging,
      tracking of super-paramagnetic particles, and measurement of tissue iron levels.
      However, R2 measurements can be confounded by several effects, particularly the
      presence of fat and macroscopic B0 field variations. Fat introduces additional
      modulations in the signal. Macroscopic field variations introduce additional
      dephasing that results in accelerated signal decay. These effects produce
      systematic errors in the resulting R2 maps and make the estimated R2 values
      dependent on the acquisition parameters. In this study, we develop a complex
      reconstruction, confounder-corrected R2 mapping technique, which addresses the
      presence of fat and macroscopic field variations for both 2D and 3D acquisitions.
      This technique extends previous chemical shift-encoded methods for R2, fat and
      water mapping by measuring and correcting for the effect of macroscopic field
      variations in the acquired signal. The proposed method is tested on several 2D
      and 3D phantom and in vivo liver, cardiac, and brain datasets.

PMID- 22161868
TI  - Photoluminescence emission and photoinduced hydrogen production driven by Pt(II)
      pyridyl complexes anchored onto mesoporous silica.

PMID- 22161867
TI  - Prevalence of carpal tunnel syndrome among dairy workers.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence of carpal
      tunnel syndrome (CTS) among dairy workers. METHODS: Sixty-six dairy parlor
      workers and 58 non-parlor workers at dairies in Texas, New Mexico, and Colorado
      participated in structured interviews regarding demographics, work history, and
      hand symptoms. All participants had nerve conduction studies performed on both
      hands across the carpal tunnel. A CTS case definition was based on the presence
      of characteristic CTS symptoms and an abnormal median mononeuropathy across the
      carpal tunnel. RESULTS: The prevalence of CTS among the dairy parlor workers was
      16.6% and 3.6% among non-parlor workers. The difference was found to be
      statistically significant (P < 0.05) with an odds ratio of 5.3, CI (1.1-25.5).
      CONCLUSIONS: The results of this study indicate that CTS is a significant
      challenge for dairy parlor workers. The prevalence of CTS was found to be
      significantly higher among dairy workers performing tasks in the milking parlor
      as opposed to workers performing tasks in other areas of the dairy farm. The
      results emphasize the need for administrative and engineering controls to limit
      the exposure to physical risk factors that are associated with upper limb
      disorders such as CTS.

PMID- 22161869
TI  - Species-specific stable isotope analysis by the hyphenation of chromatographic
      techniques with MC-ICPMS.
AB  - This work reviews the basis and all the existing publications on the hyphenation
      of chromatography-based techniques to MC-ICPMS for isotopic studies that were
      published until the end of 2010. A brief historical retrospective of the
      measurement of isotope ratios from transient signals by ICPMS with different
      sample introduction techniques is also included. The most important experimental
      parameters and data reduction strategies affecting the accurate and precise
      measurement of compound-specific isotope ratios by either HPLC or GC coupled to
      MC-ICPMS are discussed. All the applications are reported and critically reviewed
      in terms of analytical characteristics, performances, optimization, advantages
      and disadvantages and future applicability to the environmental, geochemical, or
      bioinorganic studies.

PMID- 22161870
TI  - Optimal reperfusion in ST-elevation myocardial infarction--the role of the
      coronary microcirculation.
AB  - Coronary microcirculation plays a crucial role for the outcomes of patients with
      STEMI. Although PPCI improves outcomes compared to thrombolysis, a substantial
      amount of STEMI patients do not achieve optimal myocardial reperfusion.
      Angiographic methods for assessment of reperfusion like TIMI Flow and MBG are
      easy to use but new, catheter laboratory based techniques to assess reperfusion
      have a lot of potential to assess and potentially guide management of patients
      with STEMI.

PMID- 22161871
TI  - Synergy of tendon stem cells and platelet-rich plasma in tendon healing.
AB  - Injured rat Achilles tendons were treated with botulism toxin to create a
      mechanically unloaded condition (unloaded) or left untreated (loaded), and then
      treated with phosphate-buffered saline (PBS), platelet-rich plasma (PRP), tendon
      stem cells (TSCs), or a combination (TSCs + PRP). mRNA and protein expression of
      collagen I, collagen III, tenascin C, and Smad 8 were determined by real time PCR
      and immunostaining, respectively. Loaded tendons treated with PBS, PRP, or TSCs
      for 3 or 14 days had higher collagen I mRNA expression than unloaded tendons.
      Loaded tendons treated with PBS for 3 or 14 days or with PRP for 3 days had
      higher collagen I protein levels than unloaded tendons. Loaded tendons treated
      for 3 days with PBS, for 14 days with PRP or TSCs or TSCs + PRP for 3 or 14 days
      had higher collagen III protein levels than unloaded tendons. Collagen I mRNA
      levels were higher in TSCs + PRP-treated loaded tendons compared to PBS-treated
      loaded tendons on day 3 of treatment. Based on changes in the expression of
      tendon-healing genes, our data suggest that the combination of TSCs and PRP has
      synergistic effects on tendon healing under both loaded and unloaded conditions,
      and loaded conditions improve tendon healing.

PMID- 22161872
TI  - The time and place of nostalgia: re-situating a French disease.
AB  - The history of nostalgia as a clinical category has many highly specific national
      stories. This paper traces an aspect of this history, examining aspects of
      nostalgia's changing meanings in nineteenth-century France. Nostalgia was a
      disease triggered by displacement, which became medically and politically
      important after the French Revolution, when military surgeons encountered
      epidemics of nostalgia in the armed forces. Understood as a form of pathological
      homesickness, the category straddled environmental medicine and emerging ideas
      about insanity. The diagnosis became particularly important to Ideologue writers
      as a case study in regulating and redirecting the emotions, demonstrating the
      efficacy of their new "moral" treatments and an ability to generate patriotic
      attachment to the new nation state. Over the course of the century, nostalgia
      disintegrated as a medical condition reflecting a decline in environmental
      explanations for disease within medicine, and increasingly plastic meanings
      attached to nostalgic desire.

PMID- 22161873
TI  - The pathophysiologic role of the protein kinase Cdelta pathway in the
      intervertebral discs of rabbits and mice: in vitro, ex vivo, and in vivo studies.
AB  - OBJECTIVE: Protein kinase Cdelta (PKCdelta) activation has been shown to be a
      principal rate-limiting step in matrix-degrading enzyme production in human
      articular chondrocytes. The aim of this study was to assess the role of the PKC
      pathways, specifically PKCdelta, in intervertebral disc tissue homeostasis.
      METHODS: Using in vitro, ex vivo, and in vivo techniques, we evaluated the
      pathophysiologic role of the PKCdelta pathway by examining 1) proteoglycan
      deposition, 2) matrix-degrading enzyme production and activity, 3) downstream
      signaling pathways regulated by PKCdelta, and 4) the effect on in vivo models of
      disc degeneration in genetically engineered PKCdelta-knockout mice. RESULTS:
      Studies of pathway-specific inhibitors revealed a vital role of the PKCdelta/MAPK
      (ERK, p38, JNK) axis and NF-kappaB in disc homeostasis. Accordingly, in an in
      vivo model of disc injury, PKCdelta-knockout mice were markedly resistant to disc
      degeneration. CONCLUSION: Suppression of the PKCdelta pathway may be beneficial
      in the prevention and/or treatment of disc degeneration. The results of this
      study provide evidence for a potential therapeutic role of pathway-specific
      inhibitors of the PKCdelta cascade in the future.

PMID- 22161875
TI  - Substantia nigra hypoechogenicity in Friedreich ataxia.

PMID- 22161876
TI  - [After care in Hodgkin lymphoma].

PMID- 22161878
TI  - [Christmas books for the physician].

PMID- 22161874
TI  - Spontaneous transformation of murine epithelial cells requires the early
      acquisition of specific chromosomal aneuploidies and genomic imbalances.
AB  - Human carcinomas are defined by recurrent chromosomal aneuploidies, which result
      in a tissue-specific distribution of genomic imbalances. In order to develop
      models for these genome mutations and to determine their role in tumorigenesis,
      we generated 45 spontaneously transformed murine cell lines from normal
      epithelial cells derived from bladder, cervix, colon, kidney, lung, and mammary
      gland. Phenotypic changes, chromosomal aberrations, centrosome number, and
      telomerase activity were assayed in control uncultured cells and in three
      subsequent stages of transformation. Supernumerary centrosomes, binucleate cells,
      and tetraploidy were observed as early as 48 hr after explantation. In addition,
      telomerase activity increased throughout progression. Live-cell imaging revealed
      that failure of cytokinesis, not cell fusion, promoted genome duplication.
      Spectral karyotyping demonstrated that aneuploidy preceded immortalization,
      consisting predominantly of whole chromosome losses (4, 9, 12, 13, 16, and Y) and
      gains (1, 10, 15, and 19). After transformation, focal amplifications of the
      oncogenes Myc and Mdm2 were frequently detected. Fifty percent of the transformed
      lines resulted in tumors on injection into immunocompromised mice. The phenotypic
      and genomic alterations observed in spontaneously transformed murine epithelial
      cells recapitulated the aberration pattern observed during human carcinogenesis.
      The dominant aberration of these cell lines was the presence of specific
      chromosomal aneuploidies. We propose that our newly derived cancer models will be
      useful tools to dissect the sequential steps of genome mutations during malignant
      transformation, and also to identify cancer-specific genes, signaling pathways,
      and the role of chromosomal instability in this process.

PMID- 22161879
TI  - [Adverse effects of treatment with psychotropic drugs in the elderly - special
      risks, protective mechanisms, prognosis].
AB  - Due to their multimorbidity elderly patients take multiple medications, which
      increase the risks of adverse side effects. In this patient group, main aim of
      treatment is to achieve an optimal quality of live. Unwanted effects of drugs and
      of drug combinations (polypharmacy) have carefully to be checked.

PMID- 22161880
TI  - [Elastography, the new dimension in ultrasonography].
AB  - Inflammation and neoplasia lead to an alteration of the normal tissue structure
      causing hardening of the tissue and an alteration of its elasticity. The
      elasticity modulus is a measure of the stress which is applied to tissue
      structures relative to the strain or deformation produced. Acute inflammation
      (softer tissue) will be compressed more than harder (neoplastic) tissue under the
      same pressure. This different deformation can be detected from the ultrasound
      data, analysed (autocorrelation) and displayed similar to a conventional Colour
      Doppler examination colour overlay of the conventional B-Mode image. In the
      following article elastographic applications are discussed.

PMID- 22161881
TI  - [Cystic adnexal mass].
AB  - Confirmation and clarification of an adnexal mass is a domain of transvaginal
      ultrasound. The highest hit ratio is achieved by experienced sonographers relying
      on a dedicated set of sonomorphologic criteria. Less experienced may consult
      validated scores, colour doppler findings and the tumor marker CA125. The
      assignment to one of the three groups simple cyst, benign tumor, malign tumor
      should lead to an adequate procedure (control, laparoscopy, laparotomy). Whenever
      possible to avoid unnecessary surgical interventions, simple cysts should be
      treated conservatively. Also in postmenopausal woman 50% of them resolve
      spontaneously in 60 days. Ovarian cancer screening is still an unsolved problem.
      Nearly all established methods fail because of the low prevalence of ovarian
      cancer at around 0.4%.

PMID- 22161882
TI  - [Rebound hypoxemia after oxygen therapy in acute exacerbation of chronic
      obstructive lung disease].

PMID- 22161883
TI  - [Asymptomatic facial infiltrated papules in an HIV-positive male].
AB  - A 65 year old HIV-infected patient (CDC A2, diagnosed in 07/2008) presented with
      facial, erythematous infiltrated papular lesions. Consistent with progressive
      immunodeficiency a low CD4+ T-cell count and an increase of the viral load was
      seen simultaneously and an eosinophilic pustular folliculitis (EPF) was assumed.
      Though, the lesional biopsy revealed a follicular eosinophilic infiltration and
      endotrichial hyphae, proving for an infiltrating dermatophytosis. This shows how
      an infiltrating Tinea faciei is mimicking clinically and histologically an HIV
      associated EPF of the face.

PMID- 22161884
TI  - [Not Available].

PMID- 22161885
TI  - [Not Available].

PMID- 22161887
TI  - [Nodule in the neck. CME ultrasound diagnosis 43].

PMID- 22161891
TI  - Numerical optimization of a three-channel radiofrequency coil for open, vertical
      field, MR-guided, focused ultrasound surgery using the hybrid method of
      moment/finite difference time domain method.
AB  - The numerical optimization of a three-channel radiofrequency (RF) coil with a
      physical aperture for the open, vertical-field, MR-guided, focused ultrasound
      surgery (MRgFUS) system using the hybrid method of moment (MoM)/finite difference
      time domain (FDTD) method is reported. The numerical simulation of the current
      density distribution on an RF coil with a complicated irregular structure was
      performed using MoM. The electromagnetic field simulation containing the full
      coil-tissue interactions within the region of interest was accomplished using the
      FDTD method. Huygens' equivalent box with six surfaces smoothly connected the MoM
      and FDTD method. An electromagnetic model of the human pelvic region was
      reconstructed and loaded in the FDTD zone to optimize the three-channel RF coil
      and compensate for the lower sensitivity at the vertical field. In addition, the
      numerical MoM was used to model the resonance, decoupling and impedance matching
      of the RF coil in compliance with engineering practices. A prototype RF coil was
      constructed to verify the simulation results. The results demonstrate that the
      signal-to-noise ratio and the homogeneity of the B(1) field were both greatly
      improved compared with previously published results.

PMID- 22161892
TI  - Photoredox-initiated alpha-alkylation of imines through a three-component
      radical/cationic reaction.

PMID- 22161896
TI  - Discrepancy in prostate cancer localization between biopsy and prostatectomy
      specimens in patients with unilateral positive biopsy: implications for focal
      therapy.
AB  - BACKGROUND: Unilateral ablative strategy success depends on reliable prediction
      of prostate cancer (PCA) location. We evaluated the discrepancy in PCA
      localization between unilateral positive biopsy (PBx) and radical prostatectomy
      (RP). METHODS: Between 2004 and 2008, 431 patients were diagnosed with unilateral
      PCA by 12-core PBx; 179 underwent RP and constituted our study cohort. Specimens
      were reviewed to map tumor outline and determine number of cancer foci, tumor
      volume, Gleason score (GS), zone of origin, localization, and pathologic stage.
      RESULTS: In 50 men, biopsy and prostatectomy findings correlated (unilateral
      tumor); in 129, PCA was detected in the contralateral side of the prostate. In 52
      patients, 54 clinically significant tumors were missed by biopsy. When patients
      with true unilateral and missed contralateral disease at RP were compared with
      respect to prognostic parameters no significant differences were detected. Sixty
      one of the 88 patients with preoperative low-risk disease had true unilateral (n
      = 21) or missed insignificant contralateral (n = 40) PCA; 27 had missed
      significant contralateral PCA at RP. PSA > 4 ng/ml predicted presence of
      significant bilateral disease in low-risk population (P = 0.004). Twenty-four of
      27 patients with significant bilateral cancer had PSA > 4, although 33/61 with
      unilateral or bilateral insignificant cancer had similar elevated PSA values.
      CONCLUSIONS: Twelve-core biopsy is inadequate to identify candidates for organ
      sparing therapy. Most men with unilateral positive biopsies have bilateral cancer
      at prostatectomy. Tumors missed by biopsy were clinically significant in 40% of
      patients, but no prognostic parameters could predict unilateral disease. Hemi
      ablative treatment might fail to eradicate significant lesions in the
      contralateral side.

PMID- 22161893
TI  - Thiophene-containing Pechmann dyes and related compounds: synthesis, and
      experimental and DFT characterisation.
AB  - Attaching 2-thienyl residues to the Pechmann dye core chromophore (5,5-exo
      dilactone situated around a C-C double bond) results in a novel magenta-coloured
      compound (UV/Vis spectroscopy lambda(max) =570 nm in CHCl(3)), which can be
      rearranged to a yellow 6,6-endo-dilactone (lambda(max) =462 nm in CHCl(3)).
      Single and double amidation results in pronounced redshift in the 5,5-exo series
      (violet, lambda(max) =570 nm and blue, lambda(max) =606 nm in CHCl(3),
      respectively) but pronounced blueshift in the 6,6-endo series (yellow,
      lambda(max) =424 nm and pale yellow bordering on colourless, lambda(max) =395 nm
      in CHCl(3), respectively). Incorporation of a 3-alkyl substituent on the
      thiophene ring allows for sharp increase of solubility in organic solvents
      concomitant with fine-tuning of the colour: a redshift in 5,5-exo-dilactones but
      a blueshift in 5,5-exo-dilactams. DFT computations demonstrate that both lactone
      classes are planar regardless of the presence of a 3-alkyl group. The lactam
      derivatives are non-planar: the thiophene-core chromophore dihedral angles
      increase on going from 5,5-exo to 6,6-endo and from thiophene to 3-alkyl
      thiophene. Depending on the core heteroatom (O vs. N-alkyl), ring junction (5,5
      exo vs. 6,6-endo) and 3-thiophene substituent (H vs. alkyl), two, three, four or
      six conformers are possible. All of these conformers were characterised by DFT
      and were found to be very close in energy at both IEFPCM/B3LYP/DGDZVP and
      SMD/M06/DGDZVP levels of theory. Within each conformer set, the HOMO and LUMO
      energies were within 0.05 eV and the predicted lambda(max) values (TD-DFT) within
      10 nm, and this implies low sensitivity of the optical and electronic properties
      to conformation. Cyclic voltammetry measurements of selected compounds
      demonstrated good matching to the HOMO and LUMO energies from IEFPCM/B3LYP/DGDZVP
      computations. M06-2X was the best DFT functional for TD-DFT, giving predicted
      lambda(max) values within about 20 nm.

PMID- 22161897
TI  - Controversies in parathyroid surgery: The quest for a "mini" unilateral
      parathyroid operation seems to have gone too far.

PMID- 22161898
TI  - Down-regulated SPARCL1 is associated with clinical significance in human gastric
      cancer.
AB  - BACKGROUND: SPARC-like protein 1 (SPARCL1), a member of extracelluar matrix
      glycoprotein, is involved in many physiological functions. METHODS: Tissue
      microarray (TMA) blocks were constructed based on 1,072 Chinese patients,
      containing both gastric cancer (GC) tissues and adjacent normal mucosa tissues.
      We analyzed the expression of SPARCL1 from both mRNA and protein level, using
      Real-time quantitative polymerase chain reaction (qRT-PCR), semi-quantitative
      PCR, immunohistochemistry (IHC), and Western blotting. Loss of heterozygosity
      analysis at the SPARCL1 gene locus was carried out using ten paired tumor and
      matched normal tissues. RESULTS: SPARCL1 mRNA was significantly reduced in tumor
      specimens compared with normal tissues. Down-regulation of SPARCL1 protein was
      detected in 413 cases (38.7%) of 1,072 primary gastric tumor tissues. Kaplan
      Meier survival curves demonstrated that SPARCL1-positive patients had better
      median survival time than SPARCL1-negative patients (59 months vs. 28 months, P =
      0.001). Multivariate survival analysis revealed that SPARCL1 was an independent
      prognostic factor in gastric adenocarcinoma patients with no metastasis and
      well/moderately differentiated. The incidence of LOH for each individual marker
      was 12.5% (1/8) for D4S2462, 20% (2/10) for D4S2929, and 33.3% (3/9) for SPARCL1.
      CONCLUSIONS: Our study revealed the clinical significance of SPARCL1 expression,
      providing a basis that the loss of SPARCL1 is a negative event in GC progression
      and prognosis. Furthermore, SPARCL1 protein might be considered to be a potential
      differentiation marker.

PMID- 22161899
TI  - Outcomes following oesophageal stent insertion for palliation of malignant
      strictures: A large single centre series.
AB  - BACKGROUND: Self-expanding metal stents (SEMS) are an accepted intervention for
      malignant dysphagia. Stents vary in ease of insertion, removability, migration
      and occlusion rates. This series reports the complications, morbidity and
      mortality associated with several SEMS. METHOD: A prospective database of
      patients undergoing fluoroscopic guided oesophageal stent insertion for
      malignancy between June 2001 and June 2009 was analysed. Patient demographics,
      intervention outcomes and tumour variables were correlated with stent failure and
      patient survival. Multivariate analysis was performed to evaluate predictors for
      stent failure. RESULTS: Two hundred and seventy-three stents were deployed using
      nine different types of SEMS. The median Mellow-Pinkas dysphagia score
      significantly improved from 3 to 1 post-stent insertion (P < 0.001), with a
      technical success rate of 98%. Stent complications occurred in 95 (36%) patients
      [recurrent dysphagia n = 49 (19%), migration n = 24 and occlusion n = 25].
      Multivariate analysis demonstrates that the covered Niti S stent fails
      significantly more than the double-layered Niti S stent (OR = 4, P < 0.005).
      CONCLUSION: Oesophageal stent insertion provides good palliation for malignant
      dysphagia, however recurrent dysphagia remains a problem. This major complication
      occurs more frequently with covered Niti S stents than double-layered Niti S
      stents. This finding may aid the stent choice used in advanced oesophageal
      malignancy.

PMID- 22161900
TI  - Encapsulation is a significant prognostic factor for better outcome in large
      hepatocellular carcinoma.
AB  - BACKGROUND: The aim of this study was to determine the effect of tumor
      encapsulation of hepatocellular carcinoma (HCC) on long-term survival. METHODS: A
      retrospective review of 1,240 patients who underwent hepatectomy from January
      1993 to June 2005 was conducted. There were 891 patients with tumor encapsulation
      (EC type) and 349 patients without tumor encapsulation (NC type).
      Clinicopathological factors, surgical outcome, and long-term survival were
      analyzed. RESULTS: Disease-free survival (DFS) was affected by surgical margin
      involvement, the presence of surgical complications, vascular invasion, liver
      cirrhosis, tumor encapsulation, tumor size >5 cm, tumor rupture, and the presence
      of satellite lesions (all, P < 0.05). Overall survival (OS) was also affected by
      the same parameters, except for satellite lesions. When the patients were grouped
      by tumor size >5 or <=5 cm, the protective effect of encapsulation was only
      observed when the tumor size was >5 cm [odds ratio (OR) for DFS = 0.75, P = 0.02;
      OR for OS = 0.68, P < 0.01]. CONCLUSIONS: Tumor encapsulation is a significant
      prognostic factor for HCC >5 cm.

PMID- 22161901
TI  - Overcoming the low relaxivity of gadofosveset at high field with spin locking.
AB  - The contrast agent gadofosveset, which binds reversibly to serum albumin, has a
      high longitudinal relaxivity at lower magnetic fields (<=3.0 T) but a much lower
      relaxivity at high fields. Spin locking is sensitive to macromolecular content;
      it is hypothesized that combining this technique with the albumin-binding
      properties of gadofosveset may enable increased relaxivity at high fields. In
      vitro measurements at 4.7 T found significantly higher spin-lock relaxation
      rates, R1rho (1/T1rho), when gadofosveset was serum albumin-bound than when
      unbound. R1rho values for a nonbinding contrast agent (gadopentetate dimeglumine)
      in serum albumin were similar to those for unbound gadofosveset. R2 (1/T2) values
      were also significantly higher at 4.7 T for serum albumin-bound gadofosveset than
      for unbound. Spin locking at high field generates significantly higher relaxation
      rates for gadofosveset than conventional contrast agents and may provide a method
      for differentiating free and bound molecules at these field strengths.

PMID- 22161903
TI  - Quality measurement as a prerequisite for improving hypertension control in an
      academic medical center.
AB  - BACKGROUND: Quality of care provided by the outpatient hypertension unit of a
      general hospital was measured using quality indicators (QIs) derived from
      guidelines. HYPOTHESIS: Measuring provided quality of care is an important step
      for improving it. METHODS: We enrolled 1206 patients with hypertension, 626 men
      and 580 women, with a mean age of 55.33 +/- 12.08 years. Median follow-up was 47
      months (minimum: 6 months, maximum: 349 months, interquartile range). We
      calculated the percentage of patients who achieved the targets of controlling
      blood pressure (BP), total cholesterol, low- and high-density lipoprotein
      cholesterol, triglycerides, glucose, uric acid, potassium, sodium, creatinine
      clearance, Sokolow-Lyon index, and left ventricle hypertrophy in echo between the
      first and the last visit. Patient satisfaction and the incidence of coronary
      artery disease (CAD), myocardial infarction (MI), and stroke were evaluated as
      outcome indicators. RESULTS: The BP was controlled in 40% of patients at the end
      of the study, compared with 11% at the first visit. We did not manage to achieve
      significant improvement for other QIs. A wide range of hypertensive patients and
      lack of a quality improvement program are the main reasons for low control rate.
      During follow-up, we obtained the increased incidence of cardiovascular events by
      outcome indicators such as CAD, MI, and stroke. CONCLUSIONS: Quality measurement
      shows us that the quality of provided care needs further improvement. Although we
      succeeded in controlling BP in 40% of patients, we did not manage to improve the
      other QIs. Modifying our structure and process components, we are working on
      improving outcome by achieving better control of QIs.

PMID- 22161902
TI  - Piloting a personal protection equipment distribution program among Chicago day
      laborers.
AB  - BACKGROUND: Occupational injury rates among day laborers have been estimated to
      be as high as 31%, where lack of personal protective equipment (PPE) use is
      repeatedly noted as a contributor to occupational injuries. METHODS: We
      distributed duffel bags containing nine pieces of PPE and provided training on
      their use to Chicago day laborers during six distribution sessions over two
      summers. Participants were contacted 4-8 weeks post-distribution and queried on
      PPE use. RESULTS: Of 117 participants who received the equipment, 42 completed
      the follow-up survey. Workers performed construction, demolition, and painting
      type tasks and most often used gloves, safety glasses, and respirators. Hardhats,
      coveralls, and earplugs were the least used. CONCLUSIONS: The PPE we provided was
      used during 94% of the jobs, and every one of the nine items was used. Hearing
      protection was underused. This project showed that providing PPE, along with
      training on its use, may increase PPE use among Chicago day laborers, likely
      preventing occupational injuries.

PMID- 22161905
TI  - Comparing the rheology of mulberry and "wild" silkworm spinning dopes.
AB  - Lepidoperan silks provide a superb opportunity for comparative studies of
      spinning and fiber characteristics. Comparing the four species, Bombyx mori
      (China), Actias selene (India), Antheraea yamamai (Japan), Gonometa postica
      (Africa), allows us to examine differences on the family, species, and race
      levels. Measured rheological properties were consistent with phylogenetic
      relationships and in the context of resource allocation and gland morphology. We
      propose that the thorough domestication of the mulberry silkworm B. mori for high
      silk yield has resulted in a compensatory optimization for spinning efficiency.
      This is in stark contrast to the wild silkworms, where Saturnids appear to
      minimize their energetic input toward silk output and G. postica seems to balance
      both. We conclude that comparative studies provide valuable baseline information
      for future biomimetic applications and modeling, as well as illuminating
      biologically important details of silk processing.

PMID- 22161906
TI  - [Fungal infections in the intensive care unit].
AB  - Invasive infections through to sepsis caused by fungi in intensive care units
      have increased markedly in the past few years. In the mean time almost every
      tenth case of sepsis in the intensive care unit is the result of an invasive
      fungal infection. Not only hemato-oncological or organ-transplanted patients are
      affected but increasingly also those patients who have been under intensive care
      for a considerable time and who exhibit particular risk factors. The lethality
      among the afflicted patients is high. The diagnosis of fungal infections is still
      difficult; unambiguous, highly sensitive and specific test procedures are still
      lacking. The decision for therapy must often be made empirically and as early as
      possible. In the past few years newly developed antimycotic agents have opened up
      new options for therapy.

PMID- 22161907
TI  - [DGAI-certified anesthesia seminar series focused ultrasound-ultrasound use in
      the curriculum and AINS "anesthesia Focused ultrasound" of DGAI].

PMID- 22161908
TI  - [The DGAI training module 2 in anaesthetic focussed sonography: vascular
      sonography].
AB  - Modul 2 will provide the theory and practical training of the sonographically
      guided puncture of central and peripheral veins and arteries. In doing so
      patients of all age groups are taken into consideration. Combined with the
      content of the other modules this series of workshops, which was initiated by our
      society, might be a first step in defining a new core competency of our
      specialty. The confident use of ultrasound in vascular puncture sharpens our
      dedicated professional competence and will contribute to continuously improve the
      quality and safety of anaesthesiologic patient care.

PMID- 22161909
TI  - [DGAI-certified seminar series: anaesthesia focussed echocardiography: module 4
      cardiosonography].
AB  - The use of ultrasonography in perioperative medicine has developed rapidly within
      the last decade. Today ultrasonic techniques are established methods for
      peripheral and central venous access as well as for regional anaesthesia.
      However, transthoracic ultrasonography by non-cardiologists has not yet been
      routinely established perioperatively, in intensive care medicine or in emergency
      medicine. With the current module 4: Cardiosonography of the DGAI-certified
      seminar series in Anaesthesia Focussed Sonography (AFS) it is intended to provide
      a basis for a quality assured training and implementation of transthoracic
      sonography in anaesthesia, intensive care medicine and emergency medicine.

PMID- 22161910
TI  - [Strategic planning: an important economic action for German hospitals].
AB  - In medical systems, economic issues and means of action are in the course of
      dwindling human (physicians and nurses) and financial resources are more
      important. For this reason, physicians must understand basic economic principles.
      Only in this way, there may be medical autonomy from social systems and hospital
      administrators. The current work is an approach to present a model for strategic
      planning of an anesthesia department. For this, a "strengths", "weaknesses",
      "opportunities", and "threats" (SWOT) analysis is used. This display is an
      example of an exemplary anaesthetic department.

PMID- 22161911
TI  - Asymmetric iodoamination of chalcones and 4-aryl-4-oxobutenoates catalyzed by a
      complex based on scandium(III) and a N,N'-dioxide ligand.
AB  - Highly diastereo- and enantioselective iodoamination of chalcones, 4-aryl-4
      oxobutenoates, and a trifluoro-substituted enone has been accomplished in the
      presence of a chiral N,N'-dioxide/[Sc(OTf)(3)] complex (0.5-2 mol%), delivering
      the desired vicinal anti-alpha-iodo-beta-amino carbonyl compounds
      regioselectively in high yields (up to 97%) and with excellent
      diastereoselectivities (>99:1 d.r.) and enantioselectivities (up to 99% ee).
      Enantiopure syn-alpha-iodo-beta-amino products could also be obtained from the
      isomerization of particular iodo compounds. TsNHX species (X=Cl, Br, I),
      generated from the reactions between the halo sources and TsNH(2), were further
      confirmed as the active species in the haloamination reactions involved in the
      formation of the key halonium ion intermediates. A typical haloamination
      dependency was observed, with reactivity decreasing in the order NBS>NIS?NCS.

PMID- 22161912
TI  - HDAC activity is required for BDNF to increase quantal neurotransmitter release
      and dendritic spine density in CA1 pyramidal neurons.
AB  - Molecular mechanisms involved in the strengthening and formation of synapses
      include the activation and repression of specific genes or subsets of genes by
      epigenetic modifications that do not alter the genetic code itself. Chromatin
      modifications mediated by histone acetylation have been shown to be critical for
      synaptic plasticity at hippocampal excitatory synapses and hippocampal-dependent
      memory formation. Considering that brain-derived neurotrophic factor (BDNF) plays
      an important role in synaptic plasticity and behavioral adaptations, it is not
      surprising that regulation of this gene is subject to histone acetylation changes
      during synaptic plasticity and hippocampal-dependent memory formation. Whether
      the effects of BDNF on dendritic spines and quantal transmitter release require
      histone modifications remains less known. By using two different inhibitors of
      histone deacetylases (HDACs), we describe here that their activity is required
      for BDNF to increase dendritic spine density and excitatory quantal transmitter
      release onto CA1 pyramidal neurons in hippocampal slice cultures. These results
      suggest that histone acetylation/deacetylation is a critical step in the
      modulation of hippocampal synapses by BDNF. Thus, mechanisms of epigenetic
      modulation of synapse formation and function are novel targets to consider for
      the amelioration of symptoms of intellectual disabilities and neurodegenerative
      disorders associated with cognitive and memory deficits.

PMID- 22161913
TI  - Impact messages of depressed outpatients as perceived by their significant
      others: profiles, therapeutic change, and relationship to outcome.
AB  - Whereas previous interpersonal research in depression has frequently used self
      reports, patients' impact on others is rarely analyzed. We analyzed impacts of
      180 depressed psychotherapy outpatients out of 832 diagnostically heterogeneous
      patients as rated by their significant others. Depressed patients were perceived
      as more submissive, hostile-submissive, and friendly-submissive, and as less
      dominant and friendly-dominant than patients with other principle disorders.
      After therapy, the 59 depressed patients whose significant others also provided
      data after treatment were perceived as less submissive (friendly-submissive,
      submissive, hostile-submissive) and more dominant and friendly-dominant. Whereas
      a decrease in submissiveness and hostile-submissiveness was associated with
      positive outcomes, decrease in friendly-submissiveness was unrelated. Cluster
      analyses suggested four distinct interpersonal subgroups. We discuss these
      results in terms of interpersonal theory and interpersonal assessment in
      depression therapy.

PMID- 22161914
TI  - Stereotypies: a critical appraisal and suggestion of a clinically useful
      definition.
AB  - The foundations of the clinical classification of movement disorders rest on the
      precise definition of the words used to describe the disorders. Here we argue
      that the current use of the term stereotypy falls well short of the precision
      needed for either clinical or academic use, and fails both to provide a
      clinically useful diagnostic category and to define a set of conditions that are
      linked pathophysiologically. The difficulty in defining this concept is not a new
      one as our review of the history of the term demonstrates. We synthesise this
      historical background, explore why clinicians have felt it necessary to use the
      category of stereotypy for certain movements rather than the related category of
      tics, discuss the multiple uses of the term in current research and clinical
      practice and on this basis suggest a new definition and classification.

PMID- 22161915
TI  - A comparative analysis between ultrasonometry and computer-aided tomography to
      evaluate bone healing.
AB  - An ultrasonometric and computed-tomographic study of bone healing was undertaken
      using a model of a transverse mid-shaft osteotomy of sheep tibiae fixed with a
      semi-flexible external fixator. Fourteen sheep were operated and divided into two
      groups of seven according to osteotomy type, either regular or by segmental
      resection. The animals were killed on the 90th postoperative day and the tibiae
      resected for the in vitro direct contact transverse and axial measurement of
      ultrasound propagation velocity (UV) followed by quantitative computer-aided
      tomography (callus density and volume) through the osteotomy site. The intact
      left tibiae were used for control, being examined in a symmetrical diaphyseal
      segment. Regular osteotomies healed with a smaller and more mature callus than
      resection osteotomies. Axial UV was consistently and significantly higher (p <=
      0.01) than transverse UV and both transverse and axial UV were significantly
      higher for the regular than for the segmental resection osteotomy. Transverse UV
      did not differ significantly between the intact and operated tibiae (p=0.20 for
      regular osteotomy; p=0.02 for resection osteotomy), but axial UV was
      significantly higher for the intact tibiae. Tomographic callus density was
      significantly higher for the regular than for the resection osteotomy and higher
      than both for the intact tibiae, presenting a strong positive correlation with
      UV. Callus volume presented an opposite behavior, with a negative correlation
      with UV. We conclude that UV is at least as precise as quantitative tomography
      for providing information about the healing state of both regular and resection
      osteotomy.

PMID- 22161916
TI  - Are patients deemed 'dangerous and severely personality disordered' different
      from other personality disordered patients detained in forensic settings?
AB  - BACKGROUND: In 1999, the UK government initiated a programme for the assessment
      and treatment of individuals deemed to have 'dangerous and severe personality
      disorder' (DSPD). After over 10 years of specialist service development, it is
      not clear whether DSPD patients represent a distinct group. AIMS: The aim of this
      study was to establish whether people admitted to DSPD hospital units could be
      distinguished in presentation or personality traits from people with personality
      disorder admitted to standard secure hospital services. METHODS: Thirty-eight men
      detained in high-security hospital DSPD units were compared with 62 men detained
      in conventional medium or high security hospital units, using the Psychopathy
      Checklist-Revised (PCL-R) and other standard personality disorder, clinical and
      offending measures. RESULTS: Compared with their counterparts in standard
      services, the DSPD group had higher scores on PCL-R psychopathy, significantly
      more convictions before age 18 years, greater severity of institutional violence
      and more prior crimes of sexual violence. Regression analysis confirmed that only
      PCL-R Factor 1, reflecting core interpersonal and affective features of
      psychopathy, predicted group membership. CONCLUSION: The DSPD group emerged as
      having higher psychopathy scores, but as there is currently no evidence that the
      core personality features of psychopathy are amenable to treatment, there is
      little justification for treating high-psychopathy forensic patients differently
      from those with other disorders of personality.

PMID- 22161917
TI  - Tranexamic acid in total knee replacement: a systematic review and meta-analysis.
AB  - We conducted a systematic review and meta-analysis of randomised controlled
      trials evaluating the effect of tranexamic acid (TXA) upon blood loss and
      transfusion in primary total knee replacement. The review used the generic
      evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group. A
      total of 19 trials were eligible: 18 used intravenous administration, one also
      evaluated oral dosing and one trial evaluated topical use. TXA led to a
      significant reduction in the proportion of patients requiring blood transfusion
      (risk ratio (RR) 2.56, 95% confidence interval (CI) 2.1 to 3.1, p < 0.001;
      heterogeneity I(2) = 75%; 14 trials, 824 patients). Using TXA also reduced total
      blood loss by a mean of 591 ml (95% CI 536 to 647, p < 0.001; I(2) = 78%; nine
      trials, 763 patients). The clinical interpretation of these findings is limited
      by substantial heterogeneity. However, subgroup analysis of high-dose (> 4 g) TXA
      showed a plausible consistent reduction in blood transfusion requirements (RR
      5.33; 95% CI 2.44 to 11.65, p < 0.001; I(2) = 0%), a finding that should be
      confirmed by a further well-designed trial. The current evidence from trials does
      not support an increased risk of deep-vein thrombosis (13 trials, 801 patients)
      or pulmonary embolism (18 trials, 971 patients) due to TXA administration.

PMID- 22161918
TI  - Identifying orthopaedic surgeons of the future: the inability of some medical
      students to achieve competence in basic arthroscopic tasks despite training: a
      randomised study.
AB  - The aim of this study was to investigate the effect of training on the
      arthroscopic performance of a group of medical students and to determine whether
      all students could be trained to competence. Thirty-three medical students with
      no previous experience of arthroscopy were randomised to a 'Trained' or an
      'Untrained' cohort. They were required to carry out 30 episodes of two simulated
      arthroscopic tasks (one shoulder and one knee). The primary outcome variable was
      task success at each episode. Individuals achieved competence when their learning
      curve stabilised. The secondary outcome was technical dexterity, assessed
      objectively using a validated motion analysis system. Six subjects in the
      'Untrained' cohort failed to achieve competence in the shoulder task, compared
      with one in the 'Trained' cohort. During the knee task, two subjects in each
      cohort failed to achieve competence. Based on the objective motion analysis
      parameters, the 'Trained' cohort performed better on the shoulder task (p < 0.05)
      but there was no significant difference for the knee task (p > 0.05).  Although
      specific training improved the arthroscopic performance of novices, there were
      individuals who could not achieve competence despite focused training.These
      findings may have an impact on the selection process for trainees and influence
      individual career choices.

PMID- 22161919
TI  - High complication rate in reconstruction of Paprosky type IIIa acetabular defects
      using an oblong implant with modular side plates and a hook.
AB  - We report the results of 62 hips in 62 patients (17 males, 45 females) with mean
      age of 62.4 years (37 to 81), who underwent revision of the acetabular component
      of a total hip replacement due to aseptic loosening between May 2003 and November
      2007. All hips had a Paprosky type IIIa acetabular defect. Acetabular revision
      was undertaken using a Procotyl E cementless oblong implant with modular side
      plates and a hook combined with impaction allografting.  At a mean follow-up of
      60.5 months (36 to 94) with no patients lost to follow-up and one died due to
      unrelated illness, the complication rate was 38.7%. Complications included
      aseptic loosening (19 hips), deep infection (3 hips), broken hook and side plate
      (one hip) and a femoral nerve palsy (one hip). Further revision of the acetabular
      component was required in 18 hips (29.0%) and a further four hips (6.4%) are
      currently loose and awaiting revision.  We observed unacceptably high rates of
      complication and failure in our group of patients and cannot recommend this
      implant or technique.

PMID- 22161920
TI  - Retrieval analysis of squeaking alumina ceramic-on-ceramic bearings.
AB  - This multicentre study analysed 12 alumina ceramic-on-ceramic components
      retrieved from squeaking total hip replacements after a mean of 23 months in situ
      (11 to 61). The rates and patterns of wear seen in these squeaking hips were
      compared with those seen in matched controls using retrieval data from 33
      'silent' hip replacements with similar ceramic bearings. All 12 bearings showed
      evidence characteristic of edge-loading wear. The median rate of volumetric wear
      was 3.4 mm(3)/year for the acetabular component, 2.9 mm(3)/year on the femoral
      heads and 6.3 mm(3)/year for head and insert combined. This was up to 45 times
      greater than that of previously reported silent ceramic-on-ceramic retrievals.
      The rate of wear seen in ceramic components revised for squeaking hips appears to
      be much greater than in that seen in retrievals from 'silent' hips.

PMID- 22161921
TI  - What advantage is there to be gained using large modular metal-on-metal bearings
      in routine primary hip replacement? A preliminary report of a prospective
      randomised controlled trial.
AB  - The aim of this study was to investigate the possible benefit of large-head metal
      on-metal bearing on a stem for primary hip replacement compared with a 28 mm
      diameter conventional metal-on-polyethylene bearing in a prospective randomised
      controlled trial. We investigated cemented stem behaviour between these two
      different bearings using Einzel-Bild-Rontgen-Analyse, clinical and patient
      reported measures (Harris hip score, Western Ontario and McMaster Universities
      osteoarthritis index, Short Form-36 and satisfaction) and whole blood metal ion
      levels at two years. A power study indicated that 50 hips were needed in each
      group to detect subsidence of > 5 mm at two years with a  p-value of < 0.05. 
      Significant improvement (p < 0.001) was found in the mean clinical and patient
      reported outcomes at two years for both groups. Comparison of outcomes between
      the groups at two years showed no statistically significant difference for mean
      stem migration, clinical and patient reported outcomes; except overall patient
      satisfaction which was higher for metal-on-metal group (p = 0.05). Metal ion
      levels were raised above the Medicines and Healthcare products Regulatory Agency
      advised safety level (7 ug per litre) in 20% of the metal-on-metal group and in
      one patient in metal-on-polyethylene group (who had a metal-on-metal implant on
      the contralateral side). Two patients in the metal-on-metal group were revised,
      one for pseudotumour and one for peri-prosthetic fracture.  Use of large modular
      heads is associated with a risk of raised whole blood metal ion levels despite
      using a proven bearing from resurfacing. The head-neck junction or excess stem
      micromotion are possibly the weak links warranting further research.

PMID- 22161922
TI  - Examination of ten fractured Oxford unicompartmental knee bearings.
AB  - Since the Oxford knee was first used unicompartmentally in 1982, a small number
      of bearings have fractured. Of 14 retrieved bearings, we examined ten samples
      with known durations in situ (four Phase 1, four Phase 2 and two Phase 3).
      Evidence of impingement and associated abnormally high wear (> 0.05 mm per year)
      as well as oxidation was observed in all bearings. In four samples the fracture
      was associated with the posterior radio-opaque wire. Fracture surfaces indicated
      fatigue failure, and scanning electron microscopy suggested that the crack
      initiated in the thinnest region. The estimated incidence of fracture was 3.20%
      for Phase 1, 0.74% for Phase 2, 0.35% for Phase 3, and 0% for Phase 3 without the
      posterior marker wire. The important aetiological factors for bearing fracture
      are impingement leading to high wear, oxidation, and the posterior marker wire.
      With improved surgical technique, impingement and high wear should be prevented
      and modern polyethylene may reduce the oxidation risk. A posterior marker wire is
      no longer used in the polyethylene meniscus. Therefore, the rate of fracture,
      which is now very low, should be reduced to a negligible level.

PMID- 22161923
TI  - Are current thrombo-embolic prophylaxis guidelines applicable to unicompartmental
      knee replacement?
AB  - Symptomatic and asymptomatic deep-vein thrombosis (DVT) is a common complication
      of knee replacement, with an incidence of up to 85% in the absence of
      prophylaxis. National guidelines for thromboprophylaxis in knee replacement are
      derived from total knee replacement (TKR) data. No guidelines exist specific to
      unicompartmental knee replacement (UKR). We investigated whether the type of knee
      arthroplasty (TKR or UKR) was related to the incidence of DVT and discuss the
      applicability of existing national guidelines for prophylaxis following UKR. 
      Data were collected prospectively on 3449 knee replacements, including procedure
      type, tourniquet time, surgeon, patient age, use of drains and gender. These
      variables were related to the incidence of symptomatic DVT. The overall DVT rate
      was 1.6%. The only variable that had an association with DVT was operation type,
      with TKR having a higher incidence than UKR (2.2% versus 0.3%, p < 0.001). These
      data show that the incidence of DVT after UKR is both clinically and
      statistically significantly lower than that after TKR.  TKR and UKR patients have
      different risk profiles for symptomatic DVT. The risk-benefit ratio for TKR that
      has been used to produce national guidelines may not be applicable to UKR.
      Further research is required to establish the most appropriate form of
      prophylaxis for UKR.

PMID- 22161924
TI  - The outcome at 20 years of conservatively treated 'isolated' posterior malleolar
      fractures of the ankle: a case series.
AB  - We assessed the long-term (20 years) outcome of closed reduction and
      immobilisation in 19 patients with an isolated fracture of the posterior
      malleolus of the ankle treated at a single hospital between 1985 and 1990. The
      assessments used were an Olerud functional questionnaire score, physical
      examination using a loaded dorsal and plantar range of movement measurement,
      radiological analysis of medial joint space widening, the Cedell score for
      anatomical alignment of all three malleoli, and the radiological presence of
      osteoarthritic change.  There were excellent or good results in 14 patients (74%)
      according to the Olerud score, in 18 patients (95%) according to loaded dorsal
      and plantar range of movement assessment, in 16 patients (84%) as judged by the
      Cedell score, and for osteoarthritis 18 patients (95%) had an excellent or good
      score. There were no poor outcomes. There was no correlation between the size of
      the fracture gap and the proportion of the tibiotalar contact area when compared
      with the clinical results (gap size: rho values -0.16 to 0.04, p >= 0.51;
      tibiotalar contact area: rho values -0.20 to -0.03, p >= 0.4). Conservative
      treatment of 'isolated' posterior malleolar fractures resulted in good clinical
      and radiological outcome in this series at long-term follow-up.

PMID- 22161925
TI  - Simple calcaneal bone cysts: a pilot study comparing open versus endoscopic
      curettage and grafting.
AB  - This pilot study analysed the outcome of open versus endoscopic curettage and
      bone grafting for the treatment of simple calcaneal bone cysts. A total of 26
      patients were evaluated into two equal groups: group 1 was treated with
      traditional open curettage and bone grafting and group 2 was treated with
      endoscopic curettage and percutaneous bone grafting. Cyst size, operating time,
      length of stay, time to healing, complications, further surgery and radiological
      healing were recorded and differences were statistically compared. The mean age
      of the patients was 22.9 years (18 to 28) and the mean follow-up was 28.7 months
      (24 to 36). There were no statistically significant differences in regard to age
      of patients, cyst size and the follow-up periods in the two groups. The operating
      time and mean length of stay of group 2 patients was significantly shorter than
      group 1 patients (p < 0.001). The time to healing was similar in the two groups.
      The overall success rates for groups 1 and 2 were 92.3% (12 of 13) and 100% (13
      of 13), respectively, and there were no statistically significant differences
      regarding radiological healing. This pilot study suggests that endoscopic
      curettage and percutaneous grafting is a simple and safe form of treatment, with
      similar results to those following open treatment.

PMID- 22161926
TI  - Proximal humeral fractures due to blunt trauma producing skin compromise.
AB  - We identified 16 patients with a mean age of 56.5 years (31 to 86) from a large
      consecutive series of patients with proximal humeral fractures over a 15-year
      period, who had sustained a fracture with skin compromise after a blunt injury.
      The study group represented 0.2% of 7825 proximal humeral fractures treated
      during this period and all had a displaced Neer two-part fracture pattern. Two
      patterns of skin injury were identified: in ten patients there was skin
      penetration at the time of the original injury, and the other six patients
      initially had closed injuries. These six patients had fracture fragments
      penetrating the muscular envelope to lie subcutaneously producing either early
      skin tethering (two patients) or delayed skin penetration and sinus formation
      (four patients). The pattern of injury to the soft-tissue envelope and the
      fracture pattern were similar for all injuries. Treatment of these injuries was
      determined by the initial severity of the soft-tissue injury and the medical
      status of the patient. We currently favour open reduction and internal fixation
      of these fractures wherever possible, owing to the high rate of nonunion with non
      operative management.

PMID- 22161927
TI  - The maturation of grafted bone after posterior lumbar interbody fusion with an
      interbody carbon cage: a prospective five-year study.
AB  - We evaluated the maturation of grafted bone in cases of successful fusion after a
      one- or two-level posterior lumbar interbody fusion (PLIF) using interbody carbon
      cages. We carried out a five-year prospective longitudinal radiological
      evaluation of patients using plain radiographs and CT scans. One year after
      surgery, 117 patients with an early successful fusion were selected for inclusion
      in the study. Radiological evaluation of interbody bone fusion was graded on a 4
      point scale. The mean grades of all radiological and CT assessments increased in
      the five years after surgery, and differences compared to the previous time
      interval were statistically significant for three or four years after surgery.
      Because the grafted bone continues to mature for three years after surgery, the
      success of a fusion should not be assessed until at least three years have
      elapsed. There were no significant differences in the longitudinal patterns of
      grafted bone maturity between iliac bone and local bone. However, iliac bone
      grafting may remodel faster than local bone.

PMID- 22161928
TI  - The case for early treatment of dislocations of the cervical spine with cord
      involvement sustained playing rugby.
AB  - The most common injury in rugby resulting in spinal cord injury (SCI) is cervical
      facet dislocation. We report on the outcome of a series of 57 patients with acute
      SCI and facet dislocation sustained when playing rugby and treated by reduction
      between 1988 and 2000 in Conradie Hospital, Cape Town. A total of 32 patients
      were completely paralysed at the time of reduction. Of these 32, eight were
      reduced within four hours of injury and five of them made a full recovery. Of the
      remaining 24 who were reduced after four hours of injury, none made a full
      recovery and only one made a partial recovery that was useful. Our results
      suggest that low-velocity trauma causing SCI, such as might occur in a rugby
      accident, presents an opportunity for secondary prevention of permanent SCI. In
      these cases the permanent damage appears to result from secondary injury, rather
      than primary mechanical spinal cord damage. In common with other central nervous
      system injuries where ischaemia determines the outcome, the time from injury to
      reduction, and hence reperfusion, is probably important.  In order to prevent
      permanent neurological damage after rugby injuries, cervical facet dislocations
      should probably be reduced within four hours of injury.

PMID- 22161929
TI  - Locally applied platelet-derived growth factor accelerates fracture healing.
AB  - Platelet-derived growth factor (PDGF) is known to stimulate osteoblast or
      osteoprogenitor cell activity. We investigated the effect of locally applied PDGF
      from poly-D,L-lactide (PDLLA)-coated implants on fracture healing in a rat model.
      A closed fracture of the right tibia of four-month-old Sprague-Dawley rats (n =
      40) was stabilised with implants coated with a biodegradable PDLLA versus
      implants coated with PDLLA and PDGF. Radiographs were taken throughout the study,
      and a marker of DNA activity, bromodeoxyuridine (BrdU), was injected before the
      rats were killed at three, seven and ten days. The radiographs showed
      consolidation of the callus in the PDGF-treated group compared with the control
      group at all three time points. In the PDGF-treated group, immunohistochemical
      staining of BrdU showed that the distribution of proliferating cells in all
      cellular events was higher after ten days compared with that at three and seven
      days. These results indicate that local application of PDGF from biodegradable
      PDLLA-coated implants significantly accelerates fracture healing in experimental
      animals. Further development may help fracture healing in the clinical situation.

PMID- 22161930
TI  - Assessing patients for joint replacement: can pre-operative Oxford hip and knee
      scores be used to predict patient satisfaction following joint replacement
      surgery and to guide patient selection?
AB  - We obtained pre-operative and six-month post-operative Oxford hip (OHS) and knee
      scores (OKS) for 1523 patients who underwent total hip replacement and 1784
      patients who underwent total knee replacement. They all also completed a six
      month satisfaction question.  Scatter plots showed no relationship between pre
      operative Oxford scores and six-month satisfaction scores. Spearman's rank
      correlation coefficients were -0.04 (95% confidence interval (CI) -0.09 to 0.01)
      between OHS and satisfaction and 0.04 (95% CI -0.01 to 0.08) between OKS and
      satisfaction. A receiver operating characteristic (ROC) curve analysis was used
      to identify a cut-off point for the pre-operative OHS/OKS that identifies whether
      or not a patient is satisfied with surgery. We obtained an area under the ROC
      curve of 0.51 (95% CI 0.45 to 0.56) for hip replacement and 0.56 (95% CI 0.51 to
      0.60) for knee replacement, indicating that pre-operative Oxford scores have no
      predictive accuracy in distinguishing satisfied from dissatisfied patients. In
      the NHS widespread attempts are being made to use patient-reported outcome
      measures (PROMs) data for the purpose of prioritising patients for surgery.
      Oxford hip and knee scores have no predictive accuracy in relation to post
      operative patient satisfaction. This evidence does not support their current use
      in prioritising access to care.

PMID- 22161931
TI  - Does the addition of cement improve the rate of local recurrence after curettage
      of giant cell tumours in bone?
AB  - We retrospectively compared the outcome after the treatment of giant cell tumours
      of bone either with curettage alone or with adjuvant cementation. Between 1975
      and 2008, 330 patients with a giant cell tumour were treated primarily by
      intralesional curettage, with 84 (25%) receiving adjuvant bone cement in the
      cavity. The local recurrence rate for curettage alone was 29.7% (73 of 246)
      compared with 14.3% (12 of 84) for curettage and cementation (p = 0.001). On
      multivariate analysis both the stage of disease and use of cement were
      independent significant factors associated with local recurrence. The use of
      cement was associated with a higher risk of the subsequent need for joint
      replacement. In patients without local recurrence, 18.1% (13 of 72) of those with
      cement needed a subsequent joint replacement compared to 2.3% (4 of 173) of those
      without cement (p = 0.001). In patients who developed local recurrence, 75.0% (9
      of 12) of those with previous cementation required a joint replacement, compared
      with 45.2% (33 of 73) of those without cement (p = 0.044).

PMID- 22161932
TI  - Severe crouch gait in spastic diplegia can be prevented: a population-based
      study.
AB  - We studied the prevalence of severe crouch gait over a 15-year period in a
      defined population of children with spastic diplegia and Gross Motor Function
      Classification System levels II and III, to determine if there had been a
      decrease following changes to the management of equinus gait. These changes were
      replacing observational with three-dimensional gait analysis, replacing single
      level with multilevel surgery, and replacing gastrocsoleus lengthening with
      gastrocnemius recession. Of 464 children and adolescents with spastic diplegia
      who underwent three-dimensional gait analysis, 27 had severe crouch gait.
      Seventeen of these had been managed by isolated lengthening of the gastrocsoleus.
      Following changes in the management of equinus gait, the prevalence of severe
      crouch gait decreased from 25% and stabilised at a significantly lower rate,
      fluctuating between 0% and 4% annually (p < 0.001).  We conclude that severe
      crouch gait in this population was precipitated by isolated lengthening of the
      gastrocsoleus. These findings may be relevant to other surgical populations, as
      severe crouch gait may be a useful way to monitor the quality of the surgical
      management of abnormal gait in children with cerebral palsy and spastic diplegia.

PMID- 22161933
TI  - Heterotopic ossification in Dupuytren's disease: clinical and histological
      significance.
AB  - We report the case of an 82-year-old man who underwent fasciectomy for a severe
      Dupuytren's contracture, during which an ossified lesion was encountered within
      the contracture and surrounding the neurovascular bundle. The abnormal tissue was
      removed with difficulty and heterotopic ossification was confirmed
      histologically. We believe this is the first report of heterotopic ossification
      in Dupuytren's disease.

PMID- 22161935
TI  - Safety and efficacy of extractible self-expandable metal stents in the treatment
      of Crohn's disease intestinal strictures: a prospective pilot study.
AB  - BACKGROUND: Endoscopic management of Crohn's disease (CD) intestinal strictures
      with balloon dilation is effective; however, recurrences are frequent and require
      further dilations or surgery. The use of extractible metallic stents may be as
      effective as balloon dilation with fewer recurrences. The aim was to investigate
      in a prospective pilot study the feasibility and clinical effectiveness of the
      use of extractible stents in the treatment of CD intestinal strictures. METHODS:
      In two tertiary referral centers, quiescent CD patients except for obstructive
      symptoms associated with intestinal stenosis of less than 50 mm length on
      enterography were eligible for transitory stent placement, initially planned to
      be retrieved after 8 weeks, which was secondarily reduced to 4 weeks after
      patient 3. RESULTS: Eleven patients (six males, five females, median age 34 years
      [range 18-66]) were prospectively included. The sites of intestinal stenosis were
      an ileocolonic anastomosis, an ileosigmoidic anastomosis, and the surgically
      untreated terminal ileum in eight, one, and two patients, respectively. Stent
      placement was technically successful in 10 patients. Obstructive symptoms were
      relieved in 6 out of 10 patients. Two patients needed surgery related to the
      procedure. Six downstream migrations were observed. Only one patient could have
      the stent extracted as scheduled on day 28 and remains symptom-free after 73
      months of follow-up. CONCLUSIONS: Even if stenting appears an effective technique
      in treating symptomatic CD intestinal strictures, the procedure is associated
      with a prohibitively high rate of spontaneous migrations and complications.

PMID- 22161936
TI  - Synthesis of trifluorostyrene derivatives by palladium-catalyzed cross-coupling
      of lithium trimethoxy(trifluorovinyl)borate with aryl bromides.

PMID- 22161938
TI  - [Conduct disorder - is there an evidence base for classification and treatment?].
AB  - This article concerns whether present psychiatric criteria for conduct disorder
      have sufficient predictive validity. Recent neurobiological findings are briefly
      summarized which suggest a more specific phenotyping of the early starter subtype
      of conduct disorder on the basis of neurobiological and personality correlates.
      Findings are discussed concerning deficits in neurobiological functioning with
      regard to emotion perception and emotion regulation relevant to social and
      aggressive behaviour as well as possible mediating influences of early
      psychosocial experiences on the development of neurobiological functions. The
      clinical implications for the classification, course and therapy of conduct
      disorders are also considered.

PMID- 22161939
TI  - [Nothing new since "Little Hans" and "Little Peter"? Psychotherapy for anxiety
      disorders in childhood and adolescence].
AB  - Anxiety disorders are among the most frequent psychological disorders in
      childhood and adolescence. They are characterized by early onset, tend to remain
      stable over time, and act as a significant risk factor for developing a
      psychological disorder in adulthood. Over the last few years, research has shown
      that anxiety disorders in children and adolescents can be treated effectively.
      However, to date only cognitive behavioral therapy (CBT) has received convincing
      empirical support as an effective psychotherapeutic treatment. Evidence for the
      effectiveness of other psychotherapeutic treatments such as nonbehavioral family
      therapy or psychodynamic interventions is rather scant. Recent randomized
      controlled trials (RCT) proved CBT to be effective from preschool age onwards.
      Contrary to long-held beliefs, however, the involvement of parents in a treatment
      program does not appear to be crucial to therapeutic outcome. Issues regarding
      the effectiveness of disorder-specific treatments and the combination of
      psychotherapeutic treatments with the application of selective serotonin reuptake
      inhibitors (SSRIs) are increasingly being taken up in recent studies. In addition
      to "classic" cognitive behavioural treatment programs there are some promising
      suggestions for the effectiveness of novel treatment methods such as attention
      bias modification or computer-assisted behavioral therapy.

PMID- 22161940
TI  - [Psychotherapeutic and pharmacological treatment of pediatric obsessive
      compulsive disorder].
AB  - Cognitive-behavioral therapy (CBT) and pharmacological treatments are often
      applied in cases of pediatric obsessive-compulsive disorder (OCD). Especially in
      combination both methods are particularly efficacious; nonetheless, 40 % of all
      patients treated remain symptomatic. Exposure with response prevention, based on
      the principle of habituation, is the intervention with the best evidence. More
      recent cognitive and metacognitive treatments focus on modifying expectations and
      may have the potential to improve treatment efficacy. Selective serotonin
      reuptake inhibitors (SSRIs) are the first line of treatment in severe cases of
      OCD. With treatment resistance, the SSRI should be changed, or alternatively
      clomipramine can be employed. Augmentation strategies suggest the combination of
      two SSRIs, SSRI und clomipramin, or SSRI and (atypical) neuroleptics. Following
      successful treatment, medication should be reduced very slowly. Novel treatments
      in children and adolescent have been reported for antiglutamatergic agents as
      riluzole or D-cycloserine, a partial agonist of N-methyl-D-aspartic acid (NMDA).

PMID- 22161941
TI  - [Concurrent validity of the HAWIK-IV and the Intelligence and Development Scales
      (IDS)].
AB  - OBJECTIVE: The present study examined the concurrent validity of the Hamburg
      Wechsler Intelligenztest fur Kinder - IV (HAWIK-IV; Petermann & Petermann, 2010)
      and the Intelligence and Development Scales (IDS; Grob, Meyer & Hagmann-von Arx,
      2009). METHODS: HAWIK-IV and IDS were administered in counterbalanced order to N
      = 172 children aged 6 to 11 years. The study presents the descriptive statistics,
      correlations, and an exploratory factor analysis of the data. RESULTS: There is a
      high correlation between HAWIK-IV Full Scale IQ and IDS intelligence score (r =
      .83). HAWIK-IV indices showed moderate to high correlations with the cognitive
      scales of the IDS (Cognition, Language, Mathematics). Low to absent correlations
      were found between HAWIK-IV indices and the noncognitive scales of the IDS
      (Social-Emotional Competence, Psychomotor, Achievement Motivation). The factor
      structure can be interpreted meaningfully and allows integration of the IDS
      cognitive, language, and mathematical subtests into the four HAWIK-IV indices.
      CONCLUSIONS: The results show that HAWIK-IV and IDS test results can be related
      to each other.

PMID- 22161942
TI  - [Intellectual abilities in adolescents with former ADHD diagnoses - relationships
      to current ADHD symptoms, comorbid symptoms, and medication history: results of
      an 8.5-year follow-up of the Cologne Adaptive Multimodal Treatment Study (CAMT)].
AB  - OBJECTIVE: The current analysis was conducted on 16- to 22-year-old persons who
      had received a multimodal treatment for ADHD during their childhood. The main
      objective was to analyse the relationships between current intellectual abilities
      and current ADHD symptoms, comorbid symptoms, and medication history. METHOD: In
      an 8.5-year follow-up study current intellectual ability was assessed with the
      German version of the KAIT (K-TIM). Behavioural problems were rated by parents
      and the former patients via standardized questionnaires and a semistructured
      interview. T-tests, Pearson correlations, and multiple regression analyses were
      then conducted. RESULTS: No significant correlations were found between former
      treatment with medication and current intellectual abilities. Moreover, no
      relationship was found between intellectual abilities and current ADHD symptoms
      as assessed by self- and parent-rating via questionnaires. However, adolescents
      with lower IQ did show higher scores of problematic performance behavior during
      the test. Also, a correlation was found between overall clinical judgement and
      externalizing problem behavior at home and in school. CONCLUSIONS: Only small
      correlations were found between the current residual symptoms and intelligence in
      adolescent and young adults who had received a diagnosis of ADHD in childhood.

PMID- 22161943
TI  - Perception of autonomy and connectedness prior to the onset of anorexia nervosa
      and bulimia nervosa.
AB  - OBJECTIVE: This study examines retrospective correlates of nonshared family
      environment prior to onset of disease, by means of multiple familial informants,
      among anorexia and bulimia nervosa patients. METHODS: A total of 332 participants
      was included (anorexia nervosa, restrictive type (AN-R): n = 41 plus families);
      bulimic patients (anorexia nervosa, binge-purging type; bulimia nervosa: n = 59
      plus families). The EATAET Lifetime Diagnostic Interview was used to establish
      the diagnosis; the Subjective Family Image Test was used to derive emotional
      connectedness (EC) and individual autonomy (IA). RESULTS: Bulimic and AN-R
      patients perceived significantly lower EC prior to onset of disease compared to
      their healthy sisters. Bulimic patients perceived significantly lower EC prior to
      onset of disease compared to AN-R patients and compared to their mothers and
      fathers. A low family sum - sister pairs sum comparison - of EC had a significant
      influence on the risk of developing bulimia nervosa. Contrary to expectations, AN
      R patients did not perceive significantly lower levels of IA compared to their
      sisters, prior to onset of disease. Findings of low IA in currently ill AN-R
      patients may represent a disease consequence, not a risk factor. CONCLUSIONS:
      Developmental child psychiatrists should direct their attention to disturbances
      of EC, which may be present prior to the onset of the disease.

PMID- 22161945
TI  - ADHD medications and cardiovascular risk: some heartening news.

PMID- 22161946
TI  - ADHD medications and risk of serious cardiovascular events in young and middle
      aged adults.
AB  - CONTEXT: More than 1.5 million US adults use stimulants and other medications
      labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These
      agents can increase heart rate and blood pressure, raising concerns about their
      cardiovascular safety. OBJECTIVE: To examine whether current use of medications
      prescribed primarily to treat ADHD is associated with increased risk of serious
      cardiovascular events in young and middle-aged adults. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective, population-based cohort study using electronic
      health care records from 4 study sites (OptumInsight Epidemiology, Tennessee
      Medicaid, Kaiser Permanente California, and the HMO Research Network), starting
      in 1986 at 1 site and ending in 2005 at all sites, with additional covariate
      assessment using 2007 survey data. Participants were adults aged 25 through 64
      years with dispensed prescriptions for methylphenidate, amphetamine, or
      atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2
      nonusers on study site, birth year, sex, and calendar year (443,198 total users
      and nonusers). MAIN OUTCOME MEASURES: Serious cardiovascular events, including
      myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with
      comparison between current or new users and remote users to account for potential
      healthy-user bias. RESULTS: During 806,182 person-years of follow-up (median, 1.3
      years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke
      occurred. There were 107,322 person-years of current use (median, 0.33 years),
      with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI,
      0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The
      multivariable-adjusted rate ratio (RR) of serious cardiovascular events for
      current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new
      users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The
      adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new
      use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit
      of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25
      44 years and 0.77 events per 1000 person-years at ages 45-64 years. CONCLUSIONS:
      Among young and middle-aged adults, current or new use of ADHD medications,
      compared with nonuse or remote use, was not associated with an increased risk of
      serious cardiovascular events. Apparent protective associations likely represent
      healthy-user bias.

PMID- 22161947
TI  - Isolation, characterization, and genetic profiling of subpopulations of olfactory
      ensheathing cells from the olfactory bulb.
AB  - Olfactory ensheathing cells (OECs) play a crucial role during neurogenesis of
      primary olfactory neurons. Transplantation of OECs is considered as a promising
      new therapy for central nervous system repair. Nevertheless, OECs are constituted
      of distinct subpopulations and their role during neurogenesis is not clearly
      understood. In particular, OECs from the olfactory bulb (OB) constitute a
      heterogeneous, but not yet isolated and characterized, population of cells. In
      our study, flow cytometry analyses of primary OB cultures, based on cell surface
      expression of low-affinity nerve growth factor receptor (p75), reveal the
      presence of two distinct populations of OECs. Indeed, some of them express a high
      level of p75 (P75High) and the other a low level of p75 (P75Low). Effects of OB
      microenvironment were assessed, and we were able to show that fibroblasts mediate
      the induction of these two populations through the secretion of soluble factors.
      To characterize P75High and P75Low OECs, cells were sorted based on their
      differential expression of p75. Microarray analyses revealed that P75High OECs
      overexpress genes implicated in modulation of extracellular matrix and cell
      sorting, whereas P75Low OECs overexpress genes involved in regulation of the
      inflammatory response and axonal guidance. These results permit, for the first
      time, to isolate the two distinct subpopulations of OECs from OB, and suggest
      their specific role during neurogenesis.

PMID- 22161948
TI  - Photochemically initiated oxidative carbon-carbon bond-cleavage reactivity in
      chlorodiketonate Ni(II) complexes.
AB  - Three mononuclear Ni(II) complexes containing a 2-chloro-1,3-diketonate ligand
      and supported by the 6-Ph(2)TPA chelate, as well as analogues that lack the 2
      chloro substituent on the beta-diketonate ligand, have been prepared and
      characterized. Upon irradiation at 350 nm under aerobic conditions, complexes
      containing the 2-chloro-substituted ligands undergo reactions to generate
      products resulting from oxidative cleavage, alpha-cleavage, and radical-derived
      reactions involving the 2-chloro-1,3-diketonate ligand. Mechanistic studies
      suggest that the oxidative cleavage reactivity, which leads to the production of
      carboxylic acids, is a result of the formation of superoxide, which occurs
      through reaction of reduced nickel complexes with O(2). The presence of the 2
      chloro substituent was found to be a prerequisite for oxidative carbon-carbon
      bond-cleavage reactivity, as complexes lacking this functional group did not
      undergo these reactions following prolonged irradiation. The approach toward
      investigating the oxidative reactivity of metal beta-diketonate species outlined
      herein has yielded results of relevance to the proposed mechanistic pathways of
      metalloenzyme-catalyzed beta-diketonate oxidative cleavage reactions.

PMID- 22161949
TI  - Microdrop printing of hydrogel bioinks into 3D tissue-like geometries.
AB  - An optimized 3D inkjet printing process is demonstrated for structuring alginate
      into a tissue-like microvasculature capable of supporting physiological flow
      rates. Optimizing the reaction at the single-droplet level enables wet hydrogel
      droplets to be stacked, thus overcoming their natural tendancy to spread and
      coalesce. Live cells can be patterned using this process and it can be extended
      to a range of other hydrogels. 

PMID- 22161950
TI  - Intravenous electrocardiography helps inexperienced operators to place totally
      implantable venous access device more accurately.
AB  - BACKGROUND: Proper tip position is a major determinant of totally implantable
      venous access device (TIVAD) outcome. The aim of this study is to analyze the
      potential utilization of intravenous electrocardiography (IV-ECG) to help
      inexperienced operators for TIVAD placement. PATIENTS AND METHODS: This is a
      retrospective, observational, uni-institutional study. 331 patients receiving
      TIVAD implantation from July 2008 to December 2008 were recruited. In IV-ECG
      group, IV-ECG was used to help decide catheter tip location and catheter length.
      In Landmark group, catheter length was decided by surface landmarks. Catheter tip
      position was confirmed by post-operative supine chest X-ray. RESULTS: There were
      153 patients in IV-ECG group, and 178 patients in Landmark group. No immediate
      reoperation due to catheter mal-position was noted in IV-ECG group, but it
      happened in eight patients in Landmark group. In IV-ECG group, 97.3% of the
      catheter tip located at proper position (within 2 cm from junction of right
      atrium and superior vena cava, as compared to 88.8% of the tip position in
      Landmark group was proper. The difference was statistically significant (P <
      0.05). There was no complication associated with the use of IV-ECG. CONCLUSION:
      IV-ECG is a safe and convenient method to help inexperienced operators placing
      TIVAD.

PMID- 22161951
TI  - Association of 5alpha-reductase inhibitor use and pathological features of
      prostate cancer in men undergoing radical prostatectomy.
AB  - BACKGROUND: We investigated the association of 5alpha-reductase inhibitor (5-ARI)
      treatment with pathologic and biochemical outcome among the contemporary prostate
      cancer (PCa) patients undergoing radical prostatectomy. METHODS: We reviewed
      records of 1,204 men who underwent radical prostatectomy from 2003 to 2010. We
      estimated association of 5-ARI use with high (>=7) pathologic Gleason score and
      pathologically nonorgan-confined disease (>=pT3) via logistic regression, and
      biochemical outcome via Cox proportional hazards regression. RESULTS: Of 1,204
      patients, 50 (4.2%) reported having history 5-ARI treatment before radical
      prostatectomy. Median duration of 5-ARI treatment among the 50 patients was 23.0
      months. When adjusted for various factors including age, body mass index,
      prostate-specific antigen, clinical stage, biopsy Gleason, and prostate volume,
      history of 5-ARI treatment was revealed to be significantly associated with high
      (>=7) pathologic Gleason score (P = 0.015). Also, 5-ARI use was observed to
      significantly associated with higher rates of extraprostatic extension of tumor
      (P = 0.005) and seminal vesicle invasion (P = 0.003), respectively, when adjusted
      for same variables. However, 5-ARI use was not demonstrated to be a significant
      preoperative predictor of biochemical recurrence-free survival in multivariate
      analysis (P = 0.528). CONCLUSIONS: Our results showed 5-ARI treatment may be
      associated with more aggressive PCa demonstrating higher pathologic Gleason score
      and advanced pathologic tumor stage in men undergoing radical prostatectomy.
      However, further investigations via larger-scale, prospective studies would be
      needed on the actual effect of 5-ARI treatment on PCa-specific morbidity and
      mortality.

PMID- 22161953
TI  - Can objective endpoints be manipulated in unmasked trials?

PMID- 22161952
TI  - Fast cardiac T1 mapping in mice using a model-based compressed sensing method.
AB  - Direct measurement of the longitudinal relaxation time T1 provides objective and
      quantitative diagnostic information. However, current T1 mapping methods are
      generally time consuming without the aid of fast imaging. This study used a model
      based compressed sensing method for fast cardiac T1 mapping in small animals.
      Based on the physics of magnetization recovery, the aliasing artifact associated
      with under-sampling was removed by exploiting the sparsity of the signals in the
      T1 recovery direction. Simulation study was performed to evaluate the
      reconstruction accuracy under various experimental conditions. Several approaches
      that accounted for phase variations were compared for optimized reconstruction in
      the phantom study. In vivo validation was performed on a cardiac manganese
      enhanced MRI study using mice. Accurate reconstruction of the under-sampled
      images and the resulting T1 maps were achieved in both simulation and MRI studies
      on phantom and in vivo mice. These results suggest that the current compressed
      sensing method allows fast (<80 s) T1 mapping of the mouse heart at high spatial
      resolution (234*469 MUm2).

PMID- 22161955
TI  - Like-charged residues at the ends of oligoalanine sequences might induce a chain
      reversal.
AB  - We have examined the effect of like-charged residues on the conformation of an
      oligoalanine sequence. This was facilitated by circular dichroism (CD) and NMR
      spectroscopic and differential scanning calorimetric (DSC) measurements, and
      molecular dynamics calculations of the following three alanine-based peptides: Ac
      K-(A)(5) -K-NH(2) (KAK5), Ac-K-(A)(4) -K-NH(2) (KAK4), Ac-K-(A)(3) -K-NH(2)
      (KAK3), where A and K denote alanine and lysine residues, respectively. Our
      earlier studies suggested that the presence of like-charged residues at the end
      of a short polypeptide chain composed of nonpolar residues can induce a chain
      reversal. For all three peptides, canonical molecular dynamics simulations with
      NMR-derived restraints demonstrate the presence of ensembles of structures with a
      tendency to form a chain reversal. The KAK3 peptide exhibits a bent shape with
      its ends close to each other, while KAK4 and KAK5 are more extended. In the KAK5
      peptide, the lysine residues do not have any influence on each other and are very
      mobile. Nevertheless, the tendency to form a more or less pronounced chain
      reversal is observed and it seems to be stable in all three peptides. This chain
      reversal seems to be caused by screening of the nonpolar core from the solvent by
      the hydrated charged residues.

PMID- 22161956
TI  - Cellular properties of principal neurons in the rat entorhinal cortex. II. The
      medial entorhinal cortex.
AB  - Principal neurons in different medial entorhinal cortex (MEC) layers show
      variations in spatial modulation that stabilize between 15 and 30 days
      postnatally. These in vivo variations are likely due to differences in intrinsic
      membrane properties and integrative capacities of neurons. The latter depends on
      inputs and thus potentially on the morphology of principal neurons. In this
      comprehensive study, we systematically compared the morphological and
      physiological characteristics of principal neurons in all MEC layers of newborn
      rats before and after weaning. We recorded simultaneously from up to four post
      hoc morphologically identified MEC principal neurons in vitro. Neurons in L(ayer)
      I-LIII have dendritic and axonal arbors mainly in superficial layers, and LVI
      neurons mainly in deep layers. The dendritic and axonal trees of part of LV
      neurons diverge throughout all layers. Physiological properties of principal
      neurons differ between layers. In LII, most neurons have a prominent sag
      potential, resonance and membrane oscillations. Neurons in LIII and LVI fire
      relatively regular, and lack sag potentials and membrane oscillations. LV neurons
      show the most prominent spike-frequency adaptation and highest input resistance.
      The data indicate that adult-like principal neuron types can be differentiated
      early on during postnatal development. The results of the accompanying paper, in
      which principal neurons in the lateral entorhinal cortex (LEC) were described
      (Canto and Witter,2011), revealed that significant differences between LEC and
      MEC exist mainly in LII neurons. We therefore systematically analyzed changes in
      LII biophysical properties along the mediolateral axis of MEC and LEC. There is a
      gradient in properties typical for MEC LII neurons. These properties are most
      pronounced in medially located neurons and become less apparent in more laterally
      positioned ones. This gradient continues into LEC, such that in LEC medially
      positioned neurons share some properties with adjacent MEC cells.

PMID- 22161957
TI  - High-nitrogen-based pyrotechnics: longer- and brighter-burning, perchlorate-free,
      red-light illuminants for military and civilian applications.
AB  - The full-up prototype testing of perchlorate-free, hand-held, signal illuminants
      for the US Army's M126A1 red star parachute hand-held signal is described.
      Compared to the perchlorate-containing control, the disclosed illuminants yielded
      excellent stabilities toward various ignition stimuli while offering superior
      pyrotechnic performance. Militarily, the illuminants provided further evidence
      that development of smaller hand-held signal items in an environmentally
      conscious way is a realistic and obtainable goal. The results are also important
      from the perspective of civilian fireworks, as the development of brighter,
      longer-burning, and environmentally compatible red-light-emitting pyrotechnics is
      now possible.

PMID- 22161958
TI  - [Thoracoabdominal sonography (E-FAST plus) -AI training module 5 in
      anaesthesiologist: performed focussed sonography].
AB  - Anesthesiologists and Critical Care Physicians are confronted with the
      differential diagnoses of dyspnea, complications of mechanical ventilation or
      rapid assessment of trauma patients on a nearly daily basis. This requires the
      timely diagnosis or exclusion of a wide variety of disease processes including
      pleura effusion, pneumonia, pneumothorax as well as thoracical or abdominal
      bleeding. Furthermore, the anaesthesiologist or intensivist often makes decisions
      leading to invasive procedures like thoracentesis or percutaneous dilatational
      tracheostomy. Bedside ultrasound as the "visual stethoscope" of the acute care
      physician offers an alternative to other imaging modalities like X-ray and CAT
      scan and can reduce associated high-risk transportation of mechanically
      ventilated patients. In this article, we introduce a new training module based on
      the DGAI curriculum.

PMID- 22161959
TI  - Bio-assay guided isolation of alpha-glucosidase inhibitory constituents from
      Hibiscus mutabilis leaves.
AB  - INTRODUCTION: The increasing demand for natural-product-based medicines and
      health-care products for the management of diabetes encouraged investigation of
      this commonly available Indian plant. OBJECTIVES: To establish the anti-diabetic
      (alpha-glucosidase inhibitory) activity of H. mutabilis leaf extract, isolate and
      identify the constituents responsible for the activity, and validate a HPLC
      method for quantification of the active constituents for standardisation of the
      extract. MATERIAL AND METHODS: The methanolic extract of leaves was partitioned
      between water, n-butanol and ethyl acetate. Bio-assay guided fractionation, based
      on inhibition of alpha-glucosidase, allowed isolation and identification of the
      active components. The active components were quantified using RP-HPLC-DAD
      validated for linearity, limit of detection, limit of quantification, precision,
      accuracy and robustness for this plant extract and the partitioned fractions.
      RESULTS: Ferulic acid and caffeic acid were identified as the alpha-glucosidase
      inhibitors present in H. mutabilis. They were partitioned into an ethyl acetate
      fraction. The HPLC-DAD calibration curve showed good linearity (r2 > 0.99). For
      the recovery studies the %RSD was less than 2%. The interday and intraday
      variations were found to be less than 4% RSD for retention time and response.
      CONCLUSION: The identification of alpha-glucosidase inhibition activity in H.
      mutabilis supports further investigations into the possible use of the plant for
      the management of diabetes. The HPLC method validated for these extracts will be
      useful in future research with the plant.

PMID- 22161961
TI  - Semi-parametric area under the curve regression method for diagnostic studies
      with ordinal data.
AB  - The classification accuracy of new diagnostic tests is based on receiver
      operating characteristic (ROC) curves. The area under the ROC curve (AUC) is one
      of the well-accepted summary measures for describing the accuracy of diagnostic
      tests. The AUC summary measure can vary by patient and testing characteristics.
      Thus, the performance of the test may be different in certain subpopulation of
      patients and readers. For this purpose, we propose a direct semi-parametric
      regression model for the non-parametric AUC measure for ordinal data while
      accounting for discrete and continuous covariates. The proposed method can be
      used to estimate the AUC value under degenerate data where certain rating
      categories are not observed. We will discuss the non-standard asymptotic theory,
      since the estimating functions were based on cross-correlated random variables.
      Simulation studies based on different classification models showed that the
      proposed model worked reasonably well with small percent bias and percent mean
      squared error. The proposed method was applied to the prostate cancer study to
      estimate the AUC for four readers, and the carotid vessel study with age, gender,
      history of previous stroke, and total number of risk factors as covariates, to
      estimate the accuracy of the diagnostic test in the presence of subject-level
      covariates.

PMID- 22161960
TI  - Semiautomated spleen volumetry with diffusion-weighted MR imaging.
AB  - In this article, we determined the relative accuracy of semiautomated spleen
      volumetry with diffusion-weighted (DW) MR images compared to standard manual
      volumetry with DW-MR or CT images. Semiautomated spleen volumetry using simple
      thresholding followed by 3D and 2D connected component analysis was performed
      with DW-MR images. Manual spleen volumetry was performed on DW-MR and CT images.
      In this study, 35 potential live liver donor candidates were included.
      Semiautomated volumetry results were highly correlated with manual volumetry
      results using DW-MR (r = 0.99; P < 0.0001; mean percentage absolute difference,
      1.43 +/- 0.94) and CT (r = 0.99; P < 0.0001; 1.76 +/- 1.07). Mean total
      processing time for semiautomated volumetry was significantly shorter compared to
      that of manual volumetry with DW-MR (P < 0.0001) and CT (P < 0.0001). In
      conclusion, semiautomated spleen volumetry with DW-MR images can be performed
      rapidly and accurately when compared with standard manual volumetry.

PMID- 22161962
TI  - [11C]carbon disulfide: a versatile reagent for PET radiolabelling.

PMID- 22161963
TI  - A multiresponsive, shape-persistent, and elastic supramolecular polymer network
      gel constructed by orthogonal self-assembly.
AB  - A cross-linked supramolecular polymer network gel is designed and prepared, which
      shows reversible gel-sol transitions induced by changes in pH, temperature,
      cation concentration, and metal co-ordination. The gel pore size is controlled by
      the amount of cross-linker added to the system, and the material can be molded
      into shape-persistent, free-standing objects with elastic behavior. These
      features are all due to the dynamically reversible host-guest complexation and
      good mechanical properties of the cross-linked polymer network. No single
      organogel has previously been reported to possess all of these features, making
      this supramolecular gel an unprecedentedly intelligent soft material. 

PMID- 22161964
TI  - Severe dysphagia as a presentation of Parkinson's disease.

PMID- 22161965
TI  - Amenorrhea in women treated with thalidomide:  report of two cases and literature
      review.

PMID- 22161967
TI  - Identification of 83 novel alpha-mannosidosis-associated sequence variants:
      functional analysis of MAN2B1 missense mutations.
AB  - The lysosomal storage disorder alpha-mannosidosis is caused by deficiency of the
      enzyme lysosomal alpha-mannosidase (MAN2B1). In this study, 96 disease-associated
      sequence variants were identified in 130 unrelated alpha-mannosidosis patients
      from 30 countries. Eighty-three novel variants were detected, extending the
      mutation spectrum from 42 to 125. In total, 256 of the 260 mutant alleles (98.5%)
      were identified. Most of the variants were unique to each family, however,
      c.2248C>T (p.Arg750Trp) was detected in 50 patients from 16 countries, and
      accounted for 27.3% of the disease alleles. Haplotype analysis revealed that the
      c.2248T variant was present on four MAN2B1 haplotype backgrounds, where one major
      haplotype accounted for 95% of the alleles. The distribution of the c.2248T
      associated haplotypes differed remarkably from those of the control populations,
      suggesting that c.2248C>T has occurred on a few ancestral haplotypes where the
      major haplotype subsequently has spread by founder effects. The disease
      associated missense mutations were introduced into the human MAN2B1 cDNA,
      expressed in cell culture and assayed for MAN2B1 activity. The majority of the
      variants were inactive, however, ten showed MAN2B1 activity above background, and
      more detailed studies are necessary to further evaluate the pathogenicity of
      these variants.

PMID- 22161968
TI  - Self-expanding metal stents (SEMS) for patients with advanced esophageal cancer
      in Malawi: an effective palliative treatment.
AB  - BACKGROUND AND OBJECTIVES: Esophageal cancer is common in Malawi and most
      patients are inoperable at time of diagnosis. The aim of this study was to
      prospectively evaluate palliative treatment with self-expanding metal stents
      (SEMS) in Malawi, a low-income country with limited medical resources. METHODS:
      Data of patients with advanced inoperable esophageal cancer were prospectively
      collected. Tumor and patient specifics, risk factors, dysphagia scores,
      complications, and survival were assessed. Follow-up data for 1 year or until
      death were collected from 118/143 patients (83%) during clinic visits, home
      visits, or via cell phone. RESULTS: One hundred forty-three patients were treated
      with 154 SEMS. Median survival was 210 days (95% CI: 150-262 days). Fourteen of
      118 patients with complete follow-up (11.9%) survived more than 1 year with
      longest documented survival of 406 days. The median dysphagia score improved from
      3 at the time of presentation to 0 at the time of death. Early complications
      occurred in 4.2% (6/143), late complications in 11.9% of patients (14/118). The
      procedure related mortality was 2.1% (3/143). CONCLUSIONS: SEMS is an appropriate
      palliative treatment in a resource-limited environment. For the vast majority of
      patients a single intervention provides lasting improvement of dysphagia.

PMID- 22161969
TI  - Hippocampal activity is associated with self-descriptiveness effect in memory,
      whereas self-reference effect in memory depends on medial prefrontal activity.
AB  - The self has long been regarded as a unique cognitive structure by virtue of its
      superior mnemonic abilities. Two separate effects result from this self memory
      facilitation: self-reference effect and self-descriptiveness effect in memory.
      Self-reference effect denotes that information processed with reference to the
      self is better remembered than information processed with reference to others,
      whereas self-descriptiveness effect indicates that items judged to be self
      relevant is remembered better than items judged not to be relevant to self during
      self-reference task. Although there is a compelling connection between self
      reference effect in memory and self mentalization processes indexed by the medial
      prefrontal activity, the underlying mechanisms of the self-descriptiveness effect
      in memory have remained underspecified. In the present fMRI study, we used a
      subsequent memory paradigm to examine the neural correlates of self
      descriptiveness and self-reference effect in memory. Participants encoded
      personality traits while performing self-reference and other-reference task
      (judged the descriptiveness of the traits to themselves or a famous person "Bruce
      Lee"), and then were given a test of recognition memory outside the scanner. It
      is revealed that the hippocampal activity corresponded with self-descriptiveness
      effect in memory, but the activity of the medial prefrontal cortex and perirhinal
      cortex related to self-reference effect in memory. These findings suggested that
      the memory boost for self-relevant items relies on the enhanced relational
      binding mechanisms employed during self-relevant items.

PMID- 22161970
TI  - Ring-closing metathesis in aqueous micellar medium.
AB  - Underwater exploration: The ring-closing metathesis of N,N-diallyltosylamine
      (DATs) and diallyldiethyl malonate has been studied in aqueous micellar medium,
      at room temperature, in the presence of four different gemini cationic
      surfactants and various ruthenium catalysts. For the first time, the adsorption
      mechanisms and the reaction steps involved in this heterogeneous catalytic
      process were elucidated.

PMID- 22161972
TI  - Biochemical relapse following radical prostatectomy and miR-200a levels in
      prostate cancer.
AB  - BACKGROUND: Radical prostatectomy cures the majority of men with clinically
      localized disease, but up to 30% of men relapse with rising serum PSA levels.
      Stage, Gleason grade, and pre-operative PSA levels are associated with outcome
      but do not accurately predict which individuals will relapse. MicroRNA (miRNA)
      levels are altered in cancer and are associated with progression of disease. The
      miR-200 family has roles in prostate cancer. METHODS: miR-200a levels were
      measured in 18 radical prostatectomy samples from men who did not relapse and
      from 18 who did relapse, matched for stage (all T3), grade, and PSA levels. A
      pair of cancer and normal prostate cell lines derived from the same radical
      prostatectomy specimen were transfected with miR-200a to determine the effects on
      growth, wound healing, and invasion. RESULTS: Comparing the matched samples, 11
      of the relapsers contained lower, 2 higher and 5 similar levels to the non
      relapsers. Transient transfection of miR-200a significantly reduced cell
      proliferation in prostate cancer cell lines but did not affect invasiveness.
      CONCLUSION: miR-200a overexpression reduced prostate cancer cell growth and may
      have potential, in combination with other markers, in stratifying prostate cancer
      patients for more intensive monitoring and therapy.

PMID- 22161971
TI  - Astrogliosis involves activation of retinoic acid-inducible gene-like signaling
      in the innate immune response after spinal cord injury.
AB  - Spinal cord injury (SCI) induces a glial response in which astrocytes become
      activated and produce inflammatory mediators. The molecular basis for regulation
      of glial-innate immune responses remains poorly understood. Here, we examined the
      activation of retinoic acid-inducible gene (RIG)-like receptors (RLRs) and their
      involvement in regulating inflammation after SCI. We show that astrocytes express
      two intracellular RLRs: RIG-I and melanoma differentiation-associated gene 5. SCI
      and stretch injury of cultured astrocytes stimulated RLR signaling as determined
      by phosphorylation of interferon regulatory factor 3 (IRF3) leading to production
      of type I interferons (IFNs). RLR signaling stimulation with synthetic
      ribonucleic acid resulted in RLR activation, phosphorylation of IRF3, and
      increased expression of glial fibrillary acidic protein (GFAP) and vimentin, two
      hallmarks of reactive astrocytes. Moreover, mitochondrial E3 ubiquitin protein
      ligase 1, an RLR inhibitor, decreased production of GFAP and vimentin after RIG-I
      signaling stimulation. Our findings identify a role for RLR signaling and type I
      IFN in regulating astrocyte innate immune responses after SCI.

PMID- 22161973
TI  - A discrete dysprosium trigonal prism showing single-molecule magnet behaviour.

PMID- 22161974
TI  - The assessment of the quality of the graft in an animal model for lung
      transplantation using the metabolomics 1H high-resolution magic angle spinning
      NMR spectroscopy.
AB  - Standards are needed to control the quality of the lungs from nonheart-beating
      donors as potential grafts. This was here assessed using the metabolomics 1H high
      resolution magic angle spinning NMR spectroscopy. Selective perfusion of the
      porcine bilung block was set up 30 min after cardiac arrest with cold
      Perfadex(r). Lung alterations were analyzed at 3, 6, and 8 h of cold ischemia as
      compared to baseline and to nonperfused lung. Metabolomics analysis of lung
      biopsies allowed identification of 35 metabolites. Levels of the majority of the
      metabolites increased over time at 4 degrees C without perfusion, indicating
      cellular degradation, whereas levels of glutathione decreased. When lung was
      perfused at 4 degrees C, levels of the majority of the metabolites remained
      stable, including levels of glutathione. Levels of uracil by contrast showed a
      reverse profile, as its signal increased over time in the absence of perfusion
      while being totally absent in perfused samples. Our results showed glutathione
      and uracil as potential biomarkers for the quality of the lung. The metabolomics
      1H high-resolution magic angle spinning NMR spectroscopy can be efficiently
      applied for the assessment of the quality of the lung as an original technique
      characterized by a rapid assessment of intact biopsy samples without extraction
      and can be implemented in hospital environment.

PMID- 22161976
TI  - [Palliative care for patients with non-oncologic terminal illness].

PMID- 22161975
TI  - Nonlinear GRAPPA: a kernel approach to parallel MRI reconstruction.
AB  - GRAPPA linearly combines the undersampled k-space signals to estimate the missing
      k-space signals where the coefficients are obtained by fitting to some auto
      calibration signals (ACS) sampled with Nyquist rate based on the shift-invariant
      property. At high acceleration factors, GRAPPA reconstruction can suffer from a
      high level of noise even with a large number of auto-calibration signals. In this
      work, we propose a nonlinear method to improve GRAPPA. The method is based on the
      so-called kernel method which is widely used in machine learning. Specifically,
      the undersampled k-space signals are mapped through a nonlinear transform to a
      high-dimensional feature space, and then linearly combined to reconstruct the
      missing k-space data. The linear combination coefficients are also obtained
      through fitting to the ACS data but in the new feature space. The procedure is
      equivalent to adding many virtual channels in reconstruction. A polynomial kernel
      with explicit mapping functions is investigated in this work. Experimental
      results using phantom and in vivo data demonstrate that the proposed nonlinear
      GRAPPA method can significantly improve the reconstruction quality over GRAPPA
      and its state-of-the-art derivatives.

PMID- 22161977
TI  - Single-gate bandgap opening of bilayer graphene by dual molecular doping.
AB  - Dual doping-driven perpendicular electric field with opposite directions
      remarkably increase the on/off current ratio of bilayer graphene field-effect
      transistors. This unambiguously proves that it is possible to open a bandgap with
      two molecular dopants (F4-TCNQ and NH2 -functionalized self-assembled monolayers
      (SAMs)) even in a single-gate device structure. 

PMID- 22161978
TI  - N-fused indolines through non-carbonyl-stabilized rhodium carbenoid C-H insertion
      of N-aziridinyl imines.

PMID- 22161979
TI  - [The role of anorexia nervosa in secondary osteoporosis development with the risk
      for low energy fractures].
AB  - Anorexia nervosa (AN) has in recent years become considerably more common. The
      disease primarily affects girls and young women, also boys and young men. AN is a
      risk factor for secondary osteoporosis. AN-related metabolic disturbances lead to
      diminished bone quality and increased risk of fractures. The consequences of low
      energy fractures are the main causes of death in women with AN. Hormonal
      disturbances (e.g. hypoestrogenism, increased levels of ghrelin and Y peptide,
      changes in leptin and endocannabinoid levels), as well as the mechanisms involved
      in bone resorption (RANK/RANKL/OPG system), are considered to be of great
      importance for anorectic bone quality. The risk for osteoporotic, non-vertebral
      fractures in AN patients is significantly higher than in healthy women.
      Improvement of bone mineral density is possible after substantial body mass
      increase. Weight loss, in conjunction with a well-balanced, controlled diet, is
      the key to correct peak bone mass levels, and diminishes the risk for
      osteoporosis with its consequence of low energy bone fractures.

PMID- 22161980
TI  - [Osteonecrosis of the jaw].
AB  - The paper concerns osteonecrosis of the jaw (ONJ). It is a rare but serious
      clinical condition. It can develop in patients treated in oncologic doses with
      bisphosphonates but also with denosumab. In osteoporosis ONJ seems to be very
      rare. Definition, pathogenesis, risk factors, prevention and treatment, and the
      frequency of ONJ are presented.

PMID- 22161981
TI  - [Bisphosphonates and the risk of atrial fibrillation].
AB  - Osteoporosis is a growing problem in an ageing society. It affects women of post
      menopausal age, as well as elderly subjects of both sexes, often with dysfunction
      of the cardiovascular system or with an increased risk of circulation disorders.
      It has been found that the mortality rate of subjects with osteoporosis is
      comparable to that of patients suffering from such diseases as obturative
      pulmonary disease or myocardial ischaemia. Bisphosphonates are the most
      thoroughly studied group of drugs prescribed for the treatment of osteoporosis.
      Their administration is, however, associated with a risk of adverse symptoms,
      which can occur as gastro-intestinal tract disturbances, muscular-osseous pains,
      mandible necrosis, atypical fractures and other symptoms. Recently, there has
      been discussion about an increased risk of atrial fibrillation in bisphosphonate
      using female patients. This paper focuses on this particular problem, while
      summing up the actual status of knowledge regarding possible associations of
      bisphosphonates with cardiac rhythm disturbances.

PMID- 22161982
TI  - [Vascular endothelial growth factor (VEGF) in endocrinology and oncology].
AB  - Endocrine glands are well vascularized and the structure of their vessels
      facilitates the exchange of various substances, including hormones. These glands
      are a frequent experimental model in research on VEGF and angiogenesis. VEGF
      participates in the pathogenesis of diabetes. Diabetic nephropathy is in essence
      a microvascular disease that develops as a result of a confluence of hemodynamic
      and metabolic perturbations. Diabetic retinopathy is the most common
      microvascular complication of diabetes mellitus and is the leading cause of
      blindness. In diabetic retinopathy ischemic states and hence tissue hypoxia and
      angiogenesis takes place. Participation of angiogenesis and VEGF in pathogenesis
      of neoplastic disease is described in many papers. VEGF protein and mRNA were
      found in cancers of the thyroid, bronchus, lungs, esophagus, stomach, colon,
      liver, breast, ovary, uterus, kidney, urinary bladder, in malignant tumors of the
      brain, bone. In a series of reports connections between the degree of VEGF
      expression with tumor aggressiveness and prognosis in patients have been
      reported. Richly vascularized are GEP NET. In neuroendocrine tumors strong
      expression of VEGF, Flt-1 and KDR in relation to the unchanged surrounding
      tissues has been demonstrated. Depending on the disease entity or the degree of
      its severity attempts of application the angiogenic and antiangiogenic therapy
      are being made. Antiangiogenic therapy (usually regarded as a form of cancer
      therapy) is based on: inhibitory effects of proangiogenic ligands and their
      receptors; stimulation or delivery of angiogenesis inhibitors; direct destruction
      of neoplastic tumor vasculature.

PMID- 22161983
TI  - [Commentary on an Endocrine Society clinical practice guidelines published in
      Journal of Clinical Endocrinology and Metabolism 2011; 96: 273-288].

PMID- 22161984
TI  - Prospective motion correction with continuous gradient updates in diffusion
      weighted imaging.
AB  - Despite the existence of numerous motion correction methods, head motion during
      MRI continues to be a major source of artifacts and can greatly reduce image
      quality. This applies particularly to diffusion weighted imaging, where strong
      gradients are applied during long encoding periods. These are necessary to encode
      microscopic movements. However, they also make the technique highly sensitive to
      bulk motion. In this work, we present a prospective motion correction method
      where all applied gradients are adjusted continuously to compensate for changes
      of the object position and ensure the desired phase evolution in the image
      coordinate frame. Additionally, in phantom experiments this new technique is used
      to reproduce motion artifacts with high accuracy by changing the position of the
      imaging frame relative to the measured object. In vivo measurements demonstrate
      the validity of the new correction method.

PMID- 22161985
TI  - From olefin metathesis catalyst to alcohol racemization catalyst in one step.

PMID- 22161986
TI  - Nerve sheath in longstanding fibrostenosing Crohn's disease:  is there a
      connection?

PMID- 22161987
TI  - Fragile X-associated tremor ataxia syndrome in FMR1 gray zone allele carriers.
AB  - BACKGROUND: Carriers of fragile X mental retardation 1 (FMR1) repeat expansions
      in the premutation range (55-200 CGG repeats) often develop a syndrome of kinetic
      tremor, cerebellar ataxia, and parkinsonism; designated the fragile X-associated
      tremor ataxia syndrome (FXTAS). Neurological signs have not been reported in
      carriers of gray zone (45-54 CGG repeats) expansions. METHODS/RESULTS: We
      describe 3 patients with FMR1 gray zone alleles who meet diagnostic criteria for
      FXTAS. CONCLUSIONS: Our cases suggest that the definition of the FXTAS may need
      to be broadened to include individuals with FMR1 repeat expansions in the gray
      zone. These neurological signs may be due to elevated levels of expanded CGG
      repeat FMR1 mRNA in the gray zone carriers, similar to the changes seen in
      premutation carriers with FXTAS.

PMID- 22161988
TI  - Functional assessment of TSC1 missense variants identified in individuals with
      tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by
      mutations in the TSC1 or TSC2 genes. The TSC1 and TSC2 gene products, TSC1 and
      TSC2, form a complex that inhibits the mammalian target of rapamycin (mTOR)
      complex 1 (TORC1). Previously, we demonstrated that pathogenic amino acid
      substitutions in the N-terminal domain of TSC1 (amino acids 50-224) are
      destabilizing. Here we investigate an additional 21 unclassified TSC1 variants.
      Our functional assessment identified four substitutions (p.L61R, p.G132D,
      p.F158S, and p.R204P) between amino acids 50 and 224 that reduced TSC1 stability
      and prevented the TSC1-TSC2-dependent inhibition of TORC1. In four cases (20%),
      our functional assessment did not agree with the predictions of the SIFT amino
      acid substitution analysis software. Our new data confirm our previous finding
      that the N-terminal region of TSC1 is essential for TSC1 function.

PMID- 22161989
TI  - Comparison of circumferential resection margin clearance criteria with survival
      after surgery for cancer of esophagus.
AB  - BACKGROUND: Circumferential resection margin (CRM) is widely recognized as an
      important prognostic factor in esophageal cancer. The aim of this study was to
      evaluate the clinical significance of CRM according to the current criteria of
      the Royal College of Pathologists (RCP) and the College of American Pathologists
      (CAP). METHODS: Patients (115) who underwent esophagectomy between 2000 and 2006
      were included in this retrospective study. Factors such as neo-adjuvant therapy,
      site, histological type, size, and lymph node involvement were tested to
      determine predictability of CRM involvement. Along with these, age, sex, CRM, and
      adjuvant therapy were analyzed to determine influence on survival. RESULTS: On
      the basis of CRM, patients were divided into three groups (involved, 0.1-1 mm and
      >1mm). Size (T) was the only factor strongly predictive of CRM involvement (P <
      0.001). Size (T; P = 0.04) and lymph node involvement (N; P = 0.0003) were found
      to significantly influence overall survival (OS). When patients with CRM
      (involved and 0.1-1mm) were compared with those with CRM > 1 mm, OS was
      significantly prolonged in the latter (P = 0.02). CONCLUSION: This study appears
      to lend credence to the RCP criteria for definition of CRM over the CAP criteria.

PMID- 22161990
TI  - Phagocytosis of neuronal debris by microglia is associated with neuronal damage
      in multiple sclerosis.
AB  - Neuroaxonal degeneration is a pathological hallmark of multiple sclerosis (MS)
      contributing to irreversible neurological disability. Pathological mechanisms
      leading to axonal damage include autoimmunity to neuronal antigens. In actively
      demyelinating lesions, myelin is phagocytosed by microglia and blood-borne
      macrophages, whereas the fate of degenerating or damaged axons is unclear.
      Phagocytosis is essential for clearing neuronal debris to allow repair and
      regeneration. However, phagocytosis may lead to antigen presentation and
      autoimmunity, as has been described for neuroaxonal antigens. Despite this
      notion, it is unknown whether phagocytosis of neuronal antigens occurs in MS.
      Here, we show using novel, well-characterized antibodies to axonal antigens, that
      axonal damage is associated with HLA-DR expressing microglia/macrophages
      engulfing axonal bulbs, indicative of axonal damage. Neuronal proteins were
      frequently observed inside HLA-DR(+) cells in areas of axonal damage. In vitro,
      phagocytosis of neurofilament light (NF-L), present in white and gray matter, was
      observed in human microglia. The number of NF-L or myelin basic protein (MBP)
      positive cells was quantified using the mouse macrophage cell line J774.2.
      Intracellular colocalization of NF-L with the lysosomal membrane protein LAMP1
      was observed using confocal microscopy confirming that NF-L is taken up and
      degraded by the cell. In vivo, NF-L and MBP was observed in cerebrospinal fluid
      cells from patients with MS, suggesting neuronal debris is drained by this route
      after axonal damage. In summary, neuroaxonal debris is engulfed, phagocytosed,
      and degraded by HLA-DR(+) cells. Although uptake is essential for clearing
      neuronal debris, phagocytic cells could also play a role in augmenting
      autoimmunity to neuronal antigens.

PMID- 22161991
TI  - Synthesis of bis-indole carboxamides as G-quadruplex stabilizing and inducing
      ligands.
AB  - The design and synthesis of a series of bis-indole carboxamides with varying
      amine containing side chains as G-quadruplex DNA stabilising small molecules are
      reported. Their interactions with quadruplexes have been evaluated by means of
      Forster resonance energy transfer (FRET) melting analysis, UV/Vis spectroscopy,
      circular dichroism spectroscopy and molecular modelling studies. FRET analysis
      indicates that these ligands exhibit significant selectivity for quadruplex over
      duplex DNA, and the position of the carboxamide side chains is of paramount
      importance in G-quadruplex stabilisation. UV/Vis titration studies reveal that
      bis-indole ligands bind tightly to quadruplexes and show a three- to fivefold
      preference for c-kit2 over h-telo quadruplex DNA. CD studies revealed that bis
      indole carboxamide with a central pyridine ring induces the formation of a
      single, antiparallel, conformation of the h-telo quadruplex in the presence and
      absence of added salt. The chirality of h-telo quadruplex was transferred to the
      achiral ligand (induced CD) and the formation of a preferred atropisomer was
      observed.

PMID- 22161992
TI  - Interventional loopless antenna at 7 T.
AB  - The loopless antenna magnetic resonance imaging detector is comprised of a tuned
      coaxial cable with an extended central conductor that can be fabricated at
      submillimeter diameters for interventional use in guidewires, catheters, or
      needles. Prior work up to 4.7 T suggests a near-quadratic gain in signal-to-noise
      ratio with field strength and safe operation at 3 T. Here, for the first time,
      the signal-to-noise ratio performance and radiofrequency safety of the loopless
      antenna are investigated both theoretically, using the electromagnetic method-of
      moments, and experimentally in a standard 7 T human scanner. The results are
      compared with equivalent 3 T devices. An absolute signal-to-noise ratio gain of
      5.7 +/- 1.5-fold was realized at 7 T vs. 3 T: more than 20-fold higher than at
      1.5 T. The effective field-of-view area also increased approximately 10-fold
      compared with 3 T. Testing in a saline gel phantom suggested that safe operation
      is possible with maximum local 1-g average specific absorption rates of <12 W kg(
      1) and temperature increases of <1.9 degrees C, normalized to a 4 W kg(-1)
      radiofrequency field exposure at 7 T. The antenna did not affect the power
      applied to the scanner's transmit coil. The signal-to-noise ratio gain enabled
      magnetic resonance imaging microscopy at 40-50 MUm resolution in diseased human
      arterial specimens, offering the potential of high-resolution large-field-of-view
      or endoscopic magnetic resonance imaging for targeted intervention in focal
      disease.

PMID- 22161994
TI  - An update on treatment of hepatitis C virus genotype 1 infection and viral load
      assessments.

PMID- 22161993
TI  - Hippocampal lesions can enhance discrimination learning despite normal
      sensitivity to interference from incidental information.
AB  - Spatial properties of stimuli are sometimes encoded even when incidental to the
      demands of a particular learning task. Incidental encoding of spatial information
      may interfere with learning by (i) causing a failure to generalize learning
      between trials in which a cue is presented in different spatial locations and
      (ii) adding common spatial features to stimuli that predict different outcomes.
      Hippocampal lesions have been found to facilitate acquisition of certain tasks.
      This facilitation may occur because hippocampal lesions impair incidental
      encoding of spatial information that interferes with learning. To test this
      prediction mice with lesions of the hippocampus were trained on appetitive simple
      simultaneous discrimination tasks using inserts in the goal arms of a T-maze. It
      was found that hippocampal lesioned mice were facilitated at learning the
      discriminations, but they were sensitive to changes in spatial information in a
      manner that was similar to control mice. In a second experiment it was found that
      both control and hippocampal lesioned mice showed equivalent incidental encoding
      of egocentric spatial properties of the inserts, but both groups did not encode
      the allocentric information. These results demonstrate that mice show incidental
      encoding of egocentric spatial information that decreases the ability to solve
      simultaneous discrimination tasks. The normal egocentric spatial encoding in
      hippocampal lesioned mice contradicts theories of hippocampal function that
      suggest that the hippocampus is necessary for incidental learning per se, or is
      required for modulating stimulus representations based on the relevancy of
      information. The facilitated learning suggests that the hippocampal lesions can
      enhance learning of the same qualitative information as acquired by control mice.

PMID- 22161995
TI  - Current chemical biology tools for studying protein phosphorylation and
      dephosphorylation.
AB  - Amongst different posttranslational events involved in cellular-signaling
      pathways, phosphorylation and dephosphorylation of proteins are the most
      prevalent. Aberrant regulations in the cellular phosphoproteome network are
      implicated in most major human diseases. Consequently, kinases and phosphatases
      are two of the most important groups of drug targets in medicinal research today.
      A major challenge in the understanding of protein phosphorylation and
      dephosphorylation is the sheer complexity of the phosphoproteome network and the
      lack of tools capable of studying protein phosphorylation and dephosphorylation
      as they occur in cells. We highlight herein various chemical biology tools that
      have emerged in the last decade for such studies. First, we discuss the use of
      small-molecule mimics of phosphoamino acids and their use in elucidating the
      function of protein phosphorylation and dephosphorylation. We also introduce
      recent advances in the field of activity-based protein profiling (ABPP) for
      proteome-wide detection of protein phosphorylation and dephosphorylation. We next
      discuss the key concepts in the design of peptide- and protein-based biosensors
      capable of real-time reporting of phosphorylation/dephosphorylation events.
      Finally, we highlight the application of peptide and small-molecule microarrays
      (SMMs), and their applications in high-throughput screening and discovery of new
      compounds related to phosphorylation/dephosphorylation.

PMID- 22161996
TI  - Highly efficient aerobic oxidative hydroxylation of arylboronic acids: photoredox
      catalysis using visible light.

PMID- 22161997
TI  - Folding of alternating dialkylsilylene-spaced donor-acceptor copolymers: the
      oligomer approach.
AB  - A series of oligmers with donor-acceptor pairs separated by diisopropylsilylene
      (iPr(2)Si) spacers, composed of monomer 4b, dimer 5, trimer 6, and tetramer 7,
      were synthesized to scrutinize the folding behavior. Monomer 4a with a
      dimethylsilylene (Me(2)Si) spacer was also prepared for comparison. The 4
      aminostyrene moiety was used as the donor and the stilbene moiety as the
      acceptor. Both steady-state and time-resolved fluorescence spectroscopic
      measurement were made. Regardless of the substituents on the silicon atom, the
      emission spectra of 4a and 4b exhibit both local excited (LE) emission of the
      acceptor chromophore and emission from the charge-separated state (CT emission),
      which are similar to that of the corresponding Me(2)Si-spaced copolymer 2a with
      the same donor and acceptor chromophores, but different from that of the
      copolymer with the iPr(2)Si spacer 2b. Dimer 5 behaves like 4 and 2a. As the
      chain length of the oligomers increases, the emission properties of the higher
      homologues become prone to that of 2b. Thus, tetramer 7 exhibits emission from
      the charge-transfer complex, which is essentially same as that of 2b. Moreover,
      charge-transfer absorptions emerge in 6 and 7. These results suggest that the
      folding nature of oligomers approaches that of the corresponding polymer, as the
      degree of oligomerization increases, and the electronic interactions between
      adjacent donor-acceptor pairs are controlled by the steric effect of the
      substituents on the silicon atoms and concomitant amplification of the
      stabilizing energy by extending the distance of the folding structure.

PMID- 22161998
TI  - Surviving starvation: changes accompanying starvation tolerance in a bdelloid
      rotifer.
AB  - Bdelloid rotifers survive desiccation and starvation by halting activity and
      entering a kind of dormancy. To understand the mechanisms of survival in the
      absence of food source, we studied the anatomical and ultrastructural changes
      occurring in a bdelloid species, Macrotrachela quadricornifera Milne 1886, after
      starvation for different periods. The starved rotifers present a progressive
      reduction of body size accompanied with a consistent reduction of the volume of
      the stomach syncytium, where lipid inclusions and digestive vacuoles tend to fade
      with prolonged starvation. Similar reduction occurs in the vitellarium gland, in
      which yolk granules progressively decrease in number and size. The changes
      observed in the syncytia of the stomach and the vitellarium suggest that during
      starvation M. quadricornifera uses resources diverted from the stomach syncytium
      first and from the vitellarium syncytium later, resources that are normally
      allocated to reproduction. The fine structure of starved bdelloids is compared
      with that of anhydrobiotic bdelloids, revealing that survival during either forms
      of dormancy is sustained by different physiological mechanisms.

PMID- 22162002
TI  - Identifying clusters as low-lying mimina--efficiency of stochastic and genetic
      algorithms using inexpensive electronic structure levels.
AB  - Molecular candidates possessing unconventional chemical bonding paradigms (e.g.,
      boron wheels, molecular stars, and multicenter bonding) have attracted a great
      deal of attention by the computational community. The viability of such systems
      is necessarily assessed through the identification of the lowest lying energy
      forms of a given chemical composition on the potential energy surface (PES).
      Although dozens of search algorithms have been developed, only a few are general
      and simple enough to become standard everyday procedures for this purpose. The
      simple random search and genetic algorithm (GA) are among these: but how do these
      approaches perform on typical isomeric searches? The performance of three
      specific variants for the ab initio exploration of the PES of prototype planar
      tetracoordinated and hypercoordinated carbon-containing systems C(2) Al(4) and
      CB(6) (2-) are compared. The advantages of preoptimizing with a low-cost
      semiempirical method (e.g., PM6) together with the most cost-efficient GA-based
      variant are discussed, and the trends verified by the isomer search of the larger
      Si(5) Li(7) (+) clusters.

PMID- 22162001
TI  - All-printed carbon nanotube finFETs on plastic substrates for high-performance
      flexible electronics.
AB  - The performance of all-printed flexible electronics is still much lower than
      silicon devices and significantly limits their commercially viable production.
      All-printed flexible carbon nanotube (CNT) fin field-effect transistors (FETs)
      with dielectric-wrapped CNT network are demonstrated with remarkable performance,
      making it possible to mass-produce high-performance, all-printed flexible
      electronics on large-area substrates. 

PMID- 22161999
TI  - Using the gene ontology to scan multilevel gene sets for associations in genome
      wide association studies.
AB  - Gene-set analyses have been widely used in gene expression studies, and some of
      the developed methods have been extended to genome wide association studies
      (GWAS). Yet, complications due to linkage disequilibrium (LD) among single
      nucleotide polymorphisms (SNPs), and variable numbers of SNPs per gene and genes
      per gene-set, have plagued current approaches, often leading to ad hoc "fixes."
      To overcome some of the current limitations, we developed a general approach to
      scan GWAS SNP data for both gene-level and gene-set analyses, building on score
      statistics for generalized linear models, and taking advantage of the directed
      acyclic graph structure of the gene ontology when creating gene-sets. However,
      other types of gene-set structures can be used, such as the popular Kyoto
      Encyclopedia of Genes and Genomes (KEGG). Our approach combines SNPs into genes,
      and genes into gene-sets, but assures that positive and negative effects of genes
      on a trait do not cancel. To control for multiple testing of many gene-sets, we
      use an efficient computational strategy that accounts for LD and provides
      accurate step-down adjusted P-values for each gene-set. Application of our
      methods to two different GWAS provide guidance on the potential strengths and
      weaknesses of our proposed gene-set analyses.

PMID- 22162003
TI  - Unique in utero identification of fetuses in multifetal mouse pregnancies by
      placental bidirectional arterial spin labeling MRI.
AB  - Noninvasive imaging is a critical part of the study of developing
      embryos/fetuses, particularly in the context of alterations of gene expression in
      genetically modified animals. However, in litter-bearing animals, such as mice,
      the inability to accurately identify individual embryo/fetus in utero is a major
      obstacle to longitudinal, noninvasive in vivo studies. Arterial spin labeling MRI
      was adopted here to determine the fetal order along the uterine horns in vivo,
      based on the specific pattern of dual arterial blood supply within the mouse
      uterine horns. Blood enters the mouse uterus cranially through the ovarian artery
      and caudally through the uterine artery. Saturation slices were alternately
      placed on the maternal heart or on the bifurcation point of the common iliac
      artery, thereby saturating either downward inflow via the ovarian arteries or
      upward inflow via the uterine arteries, respectively. Saturation maps provided a
      unique signature with highly significant correlation between the direction
      dependent magnetization transfer and the position of the fetuses/placentas along
      the uterine horns. The bidirectional arterial spin labeling-MRI method reported
      here opens possibilities to determine and pursue phenotypic alterations in
      fetuses and placentas in longitudinal studies of transgenic and knockout mice
      models, and for studying defects in placental vascular architecture.

PMID- 22162004
TI  - Emotional processing in Parkinson's disease: a systematic review.
AB  - Parkinson's disease provides a useful model for studying the neural substrates of
      emotional processing. The striato-thalamo-cortical circuits, like the mesolimbic
      dopamine system that modulates their function, are thought to be involved in
      emotional processing. As Parkinson's disease is histopathologically characterized
      by the selective, progressive, and chronic degeneration of the nigrostriatal and
      mesocorticolimbic dopamine systems, it can therefore serve as a model for
      assessing the functional role of these circuits in humans. In the present review,
      we begin by providing a synopsis of the emotional disturbances observed in
      Parkinson's disease. We then discuss the functional roles of the striato-thalamo
      cortical and mesolimbic circuits, ending with the conclusion that both these
      pathways are indeed involved in emotional processing.

PMID- 22162006
TI  - Dynamics and multiple stable binding modes of DNA intercalators revealed by
      single-molecule force spectroscopy.

PMID- 22162005
TI  - Commensal and probiotic bacteria influence intestinal barrier function and
      susceptibility to colitis in Nod1-/-; Nod2-/- mice.
AB  - BACKGROUND: The intestinal microbiota regulates key host functions. It is unknown
      whether modulation of the microbiota can affect a genetically determined host
      phenotype. Polymorphisms in the Nucleotide oligomerization domain (Nod)-like
      receptor family confer genetic risk for inflammatory bowel disease (IBD). We
      investigated whether the intestinal microbiota and the probiotic strain
      Bifidobacterium breve NCC2950 affect intestinal barrier function and responses to
      intestinal injury in Nod1(-/-); Nod2(-/-) mice. METHODS: Specific pathogen-free
      (SPF) Nod1(-/-); Nod2(-/-) mice and mice gnotobiotically derived with altered
      Schaedler flora (ASF) biota were used. SPF Nod1(+/-); Nod2(+/-) littermates
      (generated by crossing SPF Nod1(-/-); Nod2(-/-) and germ-free C57BL/6 mice) and
      ASF Nod1(+/-); Nod2(+/-) mice were used as controls. SPF mice were gavaged daily
      with 10(9) -CFU B. breve for 14 days before colitis induction. Denaturing
      gradient gel electrophoresis (DGGE) and real-time polymerase chain reaction (PCR)
      were used to assess microbiota composition. Intestinal permeability was assessed
      by in vitro and in vivo techniques. Expressions of epithelial apical junction
      proteins, mucin, and antimicrobial proteins were assessed by quantitative reverse
      transcription PCR (qRT-PCR) and immunofluorescence. Responses to intestinal
      injury were investigated using an acute experimental model of colitis. RESULTS:
      Under SPF conditions, Nod1(-/-); Nod2(-/-) mice had increased paracellular
      permeability, decreased E-cadherin, and lower colonic antimicrobial RegIII-gamma
      expression compared to Nod1(+/-); Nod2(+/-) littermate controls. These changes
      were associated with increased susceptibility to colitis. ASF colonization or B.
      breve supplementation normalized RegIII-gamma expression and decreased
      susceptibility to dextran sodium sulfate (DSS) colitis in Nod1(-/-); Nod2(-/-)
      mice. CONCLUSIONS: The intestinal microbiota influences colitis severity in Nod1(
      /-); Nod2(-/-) mice. The results suggest that colonization strategies with
      defined commensals or exogenous specific probiotic therapy may prevent intestinal
      inflammation in a genetically predisposed host.

PMID- 22162007
TI  - The number of pathologic lymph nodes involved is still a significant prognostic
      factor even after neoadjuvant chemoradiotherapy in esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: The correlation between the number of pathologic metastatic LNs in
      patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant
      chemoradiotherapy (NACRT) and surgical outcome has rarely been reported. We
      evaluated the correlation between the number of pathologic metastatic lymph nodes
      (LNs) and the surgical outcome in ESCC after NACRT. METHODS: Eighty-eight
      patients with ESCC who underwent NACRT followed by surgery were evaluated. The
      clinical response of NACRT was evaluated and surgical specimens of the primary
      tumor and resected LNs were analyzed clinicopathologically. RESULTS: Fewer
      pathologic metastatic LNs was associated with better survival. According to the
      number of metastatic LNs, the difference in the median survival was the largest
      between the groups when patients were divided into those with 2 and 3 metastatic
      LNs (chi(2) : 13.694, P < 0.001). With regard to clinical factors, the initial N
      status prior to treatment had the most significant impact on survival by a
      univariate analysis (P = 0.064), and the number of pathologic metastatic LNs was
      a risk factor for poor survival, with a hazard ratio of 5.128 (95% C.I.: 1.438
      18.285, P = 0.012) by a multivariate analysis. CONCLUSIONS: Of the various
      factors, the number of pathologic metastatic LNs was the strongest indicator to
      predict the patients' survival.

PMID- 22162008
TI  - Cellular properties of principal neurons in the rat entorhinal cortex. I. The
      lateral entorhinal cortex.
AB  - The lateral entorhinal cortex (LEC) provides a major cortical input to the
      hippocampal formation, equaling that of the medial entorhinal cortex (MEC). To
      understand the functional contributions made by LEC, basic knowledge of
      individual neurons, in the context of the intrinsic network, is needed. The aim
      of this study is to compare physiological and morphological properties of
      principal neurons in different LEC layers in postnatal rats. Using in vitro whole
      cell current-clamp recordings from up to four post hoc morphologically identified
      neurons simultaneously, we established that principal neurons show layer specific
      physiological and morphological properties, similar to those reported previously
      in adults. Principal neurons in L(ayer) I, LII, and LIII have the majority of
      their dendrites and axonal collaterals alone in superficial layers. LV contains
      mainly pyramidal neurons with dendrites and axons extending throughout all
      layers. A minority of LV and all principal neurons in LVI are neurons with
      dendrites confined to deep layers and axons in superficial and deep layers.
      Physiologically, input resistances and time constants of LII neurons are lower
      and shorter, respectively, than those observed in LV neurons. Fifty-four percent
      of LII neurons have sag potentials, resonance properties, and rebounds at the
      offset of hyperpolarizing current injection, whereas LIII and LVI neurons do not
      have any of these. LV neurons show prominent spike-frequency adaptation and a
      decrease in spike amplitudes in response to strong depolarization. Despite the
      well-developed interlaminar communication in LEC, the laminar differences in the
      biophysical and morphological properties of neurons suggest that their in vivo
      firing patterns and functions differ, similar to what is known for neurons in
      different MEC layers.

PMID- 22162009
TI  - Core-structure-oriented asymmetric organocatalytic substitution of 3
      hydroxyoxindoles: application in the enantioselective total synthesis of (+)
      folicanthine.

PMID- 22162010
TI  - Multilevel data storage memory using deterministic polarization control.
AB  - Multilevel non-volatile memory for high-density date storage is achieved by using
      the deterministic control of ferroelectric polarization. In a real ferroelectric
      thin-film system, eight stable and reproducible polarization states are realized
      (i.e., 3-bit data storage) by adjusting the displacement current. This approach
      can be used to triple or quadruple the memory density, even at existing feature
      scales. 

PMID- 22162011
TI  - Longitudinal and noninvasive assessment of emphysema evolution in a murine model
      using proton MRI.
AB  - Ultrashort echo time (550 MUs) MR imaging was implemented to track the emphysema
      development in mice lung challenged with elastase. Two parameters, namely, signal
      intensity and T 2, were used to monitor the disease evolution. Nine mice were
      imaged before and at 24 h as well as at 3 and 8 weeks after elastase
      instillation. Five mice instilled with saline served as controls. At week 8, the
      mean normalized signal intensity +/- SD was 0.89 +/- 0.20 for healthy controls
      and 0.64 +/- 0.10 for animals with emphysema. Similarly, a reduced value of T 2
      (1.27 +/- 0.35 ms vs 0.96 +/- 0.18 ms) was found in the emphysema group. The mean
      signal intensity drop and the reduction of T 2 were prominent at 3 weeks
      following elastase instillation and stabilized between 3 and 8 weeks. The results
      indicated an excellent agreement between MR findings and histological morphometry
      (signal intensity, r = -0.78, P = 0.004; T 2, r = -0.78, P = 0.001). This result
      shows that proton MRI allows structural changes at alveolar level to be monitored
      longitudinally. This technique, applied routinely in preclinical trials will
      represent a valuable tool for assessment of drug therapy efficacy.

PMID- 22162013
TI  - Diagnostic algorithms for liver fibrosis in hepatitis C: are they ready to avoid
      liver biopsy?

PMID- 22162012
TI  - The DNLZ/HEP zinc-binding subdomain is critical for regulation of the
      mitochondrial chaperone HSPA9.
AB  - Human mitochondrial DNLZ/HEP regulates the catalytic activity and solubility of
      the mitochondrial hsp70 chaperone HSPA9. Here, we investigate the role that the
      DNLZ zinc-binding and C-terminal subdomains play in regulating HSPA9. We show
      that truncations lacking portions of the zinc-binding subdomain (ZBS) do not
      affect the solubility of HSPA9 or its ATPase domain, whereas those containing the
      ZBS and at least 10 residues following this subdomain enhance chaperone
      solubility. Binding measurements further show that DNLZ requires its ZBS to form
      a stable complex with the HSPA9 ATPase domain, and ATP hydrolysis measurements
      reveal that the ZBS is critical for full stimulation of HSPA9 catalytic activity.
      We also examined if DNLZ is active in vivo. We found that DNLZ partially
      complements the growth of Deltazim17 Saccharomyces cerevisiae, and we discovered
      that a Zim17 truncation lacking a majority of the C-terminal subdomain strongly
      complements growth like full-length Zim17. These findings provide direct evidence
      that human DNLZ is a functional ortholog of Zim17. In addition, they implicate
      the pair of antiparallel beta-strands that coordinate zinc in Zim17/DNLZ-type
      proteins as critical for binding and regulating hsp70 chaperones.

PMID- 22162014
TI  - Optimal dose-finding designs with correlated continuous and discrete responses.
AB  - In dose-finding clinical studies, it is common that multiple endpoints are of
      interest. For instance, in phase I/II studies, efficacy and toxicity are often
      the primary endpoints, which are observed simultaneously and which need to be
      evaluated together. Motivated by this, we confine ourselves to bivariate
      responses and focus on the most analytically difficult case: a mixture of
      continuous and categorical responses. We adopt the bivariate probit dose-response
      model and quantify our goal by a utility function. We study locally optimal
      designs, two-stage optimal designs, and fully adaptive designs under different
      ethical and cost constraints in the experiments. We assess the performance of two
      stage designs and fully adaptive designs via simulations. Our simulations suggest
      that the two-stage designs are as efficient as and may be more efficient than the
      fully adaptive designs if there is a moderate sample size in the initial stage.
      In addition, two-stage designs are easier to construct and implement and thus can
      be a useful approach in practice.

PMID- 22162015
TI  - Phenalenyl-based molecules: tuning the lowest unoccupied molecular orbital to
      design a catalyst.

PMID- 22162017
TI  - Multiwfn: a multifunctional wavefunction analyzer.
AB  - Multiwfn is a multifunctional program for wavefunction analysis. Its main
      functions are: (1) Calculating and visualizing real space function, such as
      electrostatic potential and electron localization function at point, in a line,
      in a plane or in a spatial scope. (2) Population analysis. (3) Bond order
      analysis. (4) Orbital composition analysis. (5) Plot density-of-states and
      spectrum. (6) Topology analysis for electron density. Some other useful utilities
      involved in quantum chemistry studies are also provided. The built-in graph
      module enables the results of wavefunction analysis to be plotted directly or
      exported to high-quality graphic file. The program interface is very user
      friendly and suitable for both research and teaching purpose. The code of
      Multiwfn is substantially optimized and parallelized. Its efficiency is
      demonstrated to be significantly higher than related programs with the same
      functions. Five practical examples involving a wide variety of systems and
      analysis methods are given to illustrate the usefulness of Multiwfn. The program
      is free of charge and open-source. Its precompiled file and source codes are
      available from http://multiwfn.codeplex.com.

PMID- 22162018
TI  - Controlling conformations in alternating dialkylsilylene-spaced donor-acceptor
      copolymers by a cooperative Thorpe-Ingold effect and polymer folding.
AB  - A series of dialkylsilylene-spaced copolymers 6 and 7, which contain Me(2)Si and
      iPr(2)Si spacer groups, respectively, and have alternating donor and acceptor
      chromophores, have been designed and regioselectively synthesized by
      hydrosilylation. The ratio of the donor and acceptor chromophores for each repeat
      unit is 2:1, and the two donor chromophores are linked by a trimethylene bridge.
      A 4-aminostyrene moiety is used as the donor and a series of acceptor
      chromophores with different reduction potentials are employed. Both steady-state
      and kinetic measurements reveal that the photoinduced electron transfer (PET) in
      6 obeyed the Marcus theory in which normal and inverted regions are observed. On
      the other hand, the iPr(2)Si-spaced copolymers 7 exhibit absorption and emission
      from the charge-transfer complexes exclusively due to ground-state interactions
      between the donor and acceptor chromophores. The discrepancy in photophysical
      behavior may have arisen from the difference in distance between the adjacent
      donor and acceptor chromophores. The bulkiness of the substituents on the silicon
      atom (i.e., Me versus iPr) may exert the Thorpe-Ingold effect on the local
      conformation around the silicon atom. The differences in the small energetic
      barriers for each of the conformational states may be amplified by extending the
      distance of the folding structure, which results in perturbing the conformation
      of the polymers. These results suggest that the electronic interactions between
      adjacent donor-acceptor pairs in these copolymers are controlled by the
      synchronization of the substitution effect and corresponding polymeric
      structures.

PMID- 22162019
TI  - A Korean Parkinson's disease family with the LRRK2 p.Tyr1699Cys mutation showing
      clinical heterogeneity.
AB  - BACKGROUND: Although leucine-rich repeat kinase 2 (LRRK2) is the gene most
      commonly linked to autosomal dominant inherited Parkinson's disease (PD), there
      have been few reports in Asia, probably because of population-specific
      differences in allele frequencies. METHODS: We identified a large Korean PD
      family with the p.Tyr1699Cys mutation in LRRK2 and analyzed genealogical,
      clinical, and genetic data from the family. RESULTS: Although the clinical
      findings of these patients were indistinguishable from those of patients with
      sporadic PD, the patients with the p.Tyr1699Cys mutation demonstrated clinical
      heterogeneity including differences in age at onset, rate of disease progression,
      clinical phenotype, and prognosis. CONCLUSIONS: This is the first report
      describing an Asian PD family with the p.Tyr1699Cys mutation in LRRK2. The
      affected members of this family showed clinical heterogeneity.

PMID- 22162020
TI  - Traits and evolution of wing venation pattern in paraneopteran insects.
AB  - Two different patterns of wing venation are currently supposed to be present in
      each of the three orders of Paraneoptera. This is unlikely compared with the
      situation in other insects where only one pattern exists per order. We propose
      for all Paraneoptera a new and unique interpretation of wing venation pattern,
      assuming that the convex cubitus anterior gets fused with the common stem of
      median and radial veins at or very near to wing base, after separation from
      concave cubitus posterior, and re-emerges more distally from R + M stem.
      Thereafter, the vein between concave cubitus posterior and CuA is a specialized
      crossvein called "cua-cup," proximally concave and distally convex. We show that
      despite some variations, that is, cua-cup can vary from absent to hypertrophic;
      CuA can re-emerge together with M or not, or even completely disappear, this new
      interpretation explains all situations among all fossil and recent paraneopteran
      lineages. We propose that the characters "CuA fused in a common stem with R and
      M"and "presence of specialized crossvein cua-cup" are venation apomorphies that
      support the monophyly of the Paraneoptera. In the light of these characters, we
      reinterpret several Palaeozoic and early Mesozoic fossils that were ascribed to
      Paraneoptera, and confirm the attribution of several to this superorder as well
      as possible attribution of Zygopsocidae (Zygopsocus permianus Tillyard, 1935) as
      oldest Psocodea. We discuss the situation in extinct Hypoperlida and Miomoptera,
      suggesting that both orders could well be polyphyletic, with taxa related to
      Archaeorthoptera, Paraneoptera, or even Holometabola. The Carboniferous
      Protoprosbolidae is resurrected and retransferred into the Paraneoptera. The
      genus Lithoscytina is restored. The miomopteran Eodelopterum priscum Schmidt,
      1962 is newly revised and considered as a fern pinnule. In addition, the new
      paraneopteran Bruayaphis oudardi gen. nov. et sp. nov. is described fromthe Upper
      Carboniferous of France (see Supporting Information).

PMID- 22162021
TI  - Electron paramagnetic resonance monitoring of ischemia-induced myocardial oxygen
      depletion and acidosis in isolated rat hearts using soluble paramagnetic probes.
AB  - A new low-field electron paramagnetic resonance approach for noninvasive
      measurements of myocardial oxygen tension and tissue acidity was developed. The
      approach was applied to monitor myocardial pO(2) and pH in a model of global no
      flow ischemia (30 min) and reperfusion in isolated perfused rat hearts. The
      myocardial oxygen measurements were performed using deuterated Finland trityl
      radical probe. A rapid decrease in myocardial pO(2) from 160 mmHg to about 2 +/-
      1 mmHg was observed within the first minute of ischemia followed by incomplete
      restoration of pO(2) to 50 mmHg during 30 min of reperfusion. The lower oxygen
      concentration after ischemia was attributed to the 50% reduction in coronary flow
      after ischemia as a consequence of myocardial ischemia and reperfusion damage.
      Myocardial pH measurements using a specially designed imidazoline pH-sensitive
      nitroxide showed severe myocardial acidification to pH 6.25 during 30 min of
      ischemia. Preconditioning of the hearts with two 5-min periods of ischemia
      significantly reduced the acidification of myocardial tissue during sustained
      ischemia. Noninvasive electron paramagnetic resonance monitoring of myocardial
      oxygenation and pH may provide important insights into the mechanisms of ischemia
      and reperfusion injury and a background for development of new therapeutic
      approaches.

PMID- 22162022
TI  - Evidence for an increase in trisomy 21 (Down syndrome) in Europe after the
      Chernobyl reactor accident.
AB  - The objective of this study is to investigate the prevalence of Down syndrome
      (DS) associated with Chernobyl fallout. Maternal age-adjusted DS data and
      corresponding live birth data from the following seven European countries or
      regions were analyzed: Bavaria and West Berlin in Germany, Belarus, Hungary, the
      Lothian Region of Scotland, North West England, and Sweden from 1981 to 1992. To
      assess the underlying time trends in the DS occurrence, and to investigate
      whether there have been significant changes in the trend functions after
      Chernobyl, we applied logistic regression allowing for peaks and jumps from
      January 1987 onward. The majority of the trisomy 21 cases of the previously
      reported, highly significant January 1987 clusters in Belarus and West Berlin
      were conceived when the radioactive clouds with significant amounts of
      radionuclides with short physical half-lives, especially (131)iodine, passed over
      these regions. Apart from this, we also observed a significant longer lasting
      effect in both areas. Moreover, evidence for long-term changes in the DS
      prevalence in several other European regions is presented and explained by
      exposure, especially to (137)Cs. In many areas, (137)Cs uptake reached its
      maximum one year after the Chernobyl accident. Thus, the highest increase in
      trisomy 21 should be observed in 1987/1988, which is indeed the case. Based on
      the fact that maternal meiosis is an error prone process, the assumption of a
      causal relationship between low-dose irradiation and nondisjunction is the most
      likely explanation for the observed increase in DS after the Chernobyl reactor
      accident.

PMID- 22162023
TI  - Electrochemical "signal-on" reporter for amyloid aggregates.
AB  - The synthesis and characterization of four new Ferrocene (Fc) bioconjugates,
      bearing a podant (Lys)-Leu-Val-Phe-Phe motif, namely the hydrophobic sequence of
      amyloid-beta-peptides (Abeta), is reported. The Fc-peptide conjugates are
      characterized by a reversible redox activity and the ability to undergo
      hydrophobic and hydrogen bonding interactions. Biomolecular interactions between
      Fc-bioconjugates with Abeta(12-28) fragments were studied by circular dichroism
      (CD), transmission electron microscopy (TEM), and electrochemistry. All four Fc
      peptides interacted favourable with Abeta(12-28) and prevented fibril formation,
      the extent of which depended on the length of the peptide and the nature of the C
      terminal group. The aggregates obtained for the Abeta(12-28)/Fc-peptide mixtures
      range from short fibrils to spherical aggregates. We demonstrated that in
      solution the peptide sequence and peptide charge affect the biomolecular
      interactions. Fc-peptide interactions with immobilized Abeta(12-28)-Cys films on
      Au surfaces were detected by measuring the current response of the Fc redox
      process. The formal redox potential, E(0), at ~440 (10) mV and i(pc)/i(pa) at 0.9
      were observed characteristic for the monosubstituted Fc-derivative undergoing a
      one-electron redox process. On the surface, methyl ester-protected Fc-peptides (1
      and 3) interacted only weakly with Abeta(12-28)-Cys films, giving rise to minimal
      redox activity. In contrast, charged Fc-peptides (2 and 4) gave a significant
      electrochemical readout following the interaction with Abeta(12-28)-Cys films.
      Interestingly, the Fc-peptide charge dictates the surface-assisted interactions,
      while hydrophobic and ionic effects contribute to the overall solution behaviour
      of the Fc-bioconjugates with Abeta(12-28).

PMID- 22162024
TI  - Genetic approaches to study glial cells in the rodent brain.
AB  - The development, function, and pathology of the brain depend on interactions of
      neurons and different types of glial cells, namely astrocytes, oligodendrocytes,
      microglia, and ependymal cells. Understanding neuron-glia interactions in vivo
      requires dedicated experimental approaches to manipulate each cell type
      independently. In this review, we first summarize techniques that allow for cell
      specific gene modification including targeted mutagenesis and viral transduction.
      In the second part, we describe the genetic models that allow to target the main
      glial cell types in the central nervous system. The existing arsenal of
      approaches to study glial cells in vivo and its expansion in the future are key
      to understand neuron-glia interactions under normal and pathologic conditions.

PMID- 22162026
TI  - Organically grown tomato (Lycopersicon esculentum Mill.): bioactive compounds in
      the fruit and infection with Phytophthora infestans.
AB  - BACKGROUND: Tomato fruits are characterized by a good nutritional profile,
      including different bioactive compounds such as carotenoids, phenolic compounds
      and ascorbic acid. The objective of this study was to analyze the content of
      bioactive compounds in the fruit and the infection by Phytophthora infestans of
      28 tomato genotypes from organic outdoor production. The relationship between
      bioactive compounds in the fruit and infection with P. infestans was estimated.
      Field experiments were carried out in 2004 and 2005 at two locations in central
      Germany. RESULTS: Significant variation among genotypes, locations and years was
      observed for the content of lycopene, ascorbic acid, total phenolic compounds,
      antioxidant capacity and the infection level of P. infestans. Antioxidant
      capacity seemed to be influenced mainly by the phenolics and was highest in small
      fruits, which were less infected with P. infestans. CONCLUSION: The large genetic
      variation among tomato genotypes for the content of bioactive compounds in their
      fruit allows for selection gains. None of the investigated bioactive compounds
      can be recommended for the indirect selection for increased field resistance
      against P. infestans.

PMID- 22162025
TI  - Gene expression profiling identifies mechanisms of protection to recurrent
      trinitrobenzene sulfonic acid colitis mediated by probiotics.
AB  - BACKGROUND: Host-microbiota interactions in the intestinal mucosa play a major
      role in intestinal immune homeostasis and control the threshold of local
      inflammation. The aim of this study was to evaluate the efficacy of probiotics in
      the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis model and gain
      more insight into protective mechanisms. METHODS: Moderate chronic inflammation
      of the colon was induced in BALB/c mice by repetitive intrarectal challenges with
      TNBS. Administration of probiotics started 2 weeks before colitis induction and
      was continued throughout colitis development. RESULTS: Long-term administration
      of Lactobacillus plantarum NCIMB8826 or the probiotic mixture VSL#3 reduced
      intestinal inflammation induced by TNBS, evident from improved colon morphology
      and less influx of innate (CD11b(+) ) and adaptive (CD4(+) /CD8(+) ) immune cells
      in the intestinal mucosa and decreased proinflammatory serum cytokines
      (interferon-gamma [IFN-gamma], interleukin [IL]-17, IL-1beta, monocyte
      chemoattractant protein [MCP]-1) in probiotic-treated mice. Genomewide expression
      analysis of colonic tissues using microarrays revealed differences in expression
      of genes related to inflammation and immune processes between untreated and
      probiotic treated mice. Principal component analysis revealed that probiotic
      treatment resulted in a shift of gene expression profiles toward those of healthy
      controls. Effects of probiotics on colonic gene expression were most profound
      during active inflammation, in particular on gene clusters related to mast cells
      and antimicrobial peptides. The results were substantiated by suppression of
      chemokine gene expression. CONCLUSIONS: Our data are in favor of a model in which
      probiotics downregulate expression of chemokines in the colon, thereby decreasing
      influx of inflammatory cells and rendering mice resistant to the induction of
      colitis.

PMID- 22162027
TI  - Editorial: baby boomers and virology.

PMID- 22162028
TI  - Catalytic asymmetric [3+2] annulation of allylsilanes with isatins: synthesis of
      spirooxindoles.

PMID- 22162029
TI  - Adding spatial control to click chemistry: phototriggered Diels-Alder surface
      (bio)functionalization at ambient temperature.

PMID- 22162030
TI  - Chiral nematic fluids as masks for lithography.
AB  - A lithographic scheme is reported that uses a cholesteric liquid crystal with its
      helical axis in the plane of the sample as a "mask" for imprinting patterns in a
      photoresist over a large area. On the application of an electric field the
      cholesteric liquid crystals produce a texture that acts as a lattice of
      cylindrical lenses for one polarization of a light beam. This is used in
      photolithography to create parallel lines over large areas. 

PMID- 22162031
TI  - Evaluation of protein-ligand binding free energy focused on its entropic
      components.
AB  - The binding free energy for FK506-binding protein-ligand systems is evaluated as
      a sum of two entropic components, the water-entropy gain, and the configurational
      entropy loss for the protein and ligand molecules upon the binding. The two
      entropic components are calculated using morphometric thermodynamics combined
      with a statistical-mechanical theory for molecular liquids and the normal mode
      analysis, respectively. We find that there is an excellent correlation between
      the calculated and experimental values of the binding free energy. This result is
      compared with those of several other binding-free energy calculation methods,
      including MM-PB/SA. The binding can well be elucidated by competition of the two
      entropic components. Upon the protein-ligand binding, the total volume available
      to the translational displacement of the coexisting water molecules increases,
      leading to an increase in the number of accessible configurations of the water.
      The water-entropy gain, by which the binding is driven, originates primarily from
      this effect. This study sheds new light on the theoretical prediction of the
      protein-ligand binding free energy.

PMID- 22162032
TI  - Protein unfolding and degradation by the AAA+ Lon protease.
AB  - AAA+ proteases employ a hexameric ring that harnesses the energy of ATP binding
      and hydrolysis to unfold native substrates and translocate the unfolded
      polypeptide into an interior compartment for degradation. What determines the
      ability of different AAA+ enzymes to unfold and thus degrade different native
      protein substrates is currently uncertain. Here, we explore the ability of the E.
      coli Lon protease to unfold and degrade model protein substrates beginning at N
      terminal, C-terminal, or internal degrons. Lon has historically been viewed as a
      weak unfoldase, but we demonstrate robust and processive unfolding/degradation of
      some substrates with very stable protein domains, including mDHFR and titin(I27)
      . For some native substrates, Lon is a more active unfoldase than related AAA+
      proteases, including ClpXP and ClpAP. For other substrates, this relationship is
      reversed. Thus, unfolding activity does not appear to be an intrinsic enzymatic
      property. Instead, it depends on the specific protease and substrate, suggesting
      that evolution has diversified rather than optimized the protein unfolding
      activities of different AAA+ proteases.

PMID- 22162033
TI  - Investigating the magnetic susceptibility properties of fresh human blood for
      noninvasive oxygen saturation quantification.
AB  - Quantification of blood oxygen saturation on the basis of a measurement of its
      magnetic susceptibility demands knowledge of the difference in volume
      susceptibility between fully oxygenated and fully deoxygenated blood
      (Deltachi(do) ). However, two very different values of Deltachi(do) are currently
      in use. In this work we measured Deltachi(do) as well as the susceptibility of
      oxygenated blood relative to water, Deltachi(oxy) , by MR susceptometry in
      samples of freshly drawn human blood oxygenated to various levels, from 6 to 98%
      as determined by blood gas analysis. Regression analysis yielded 0.273 +/- 0.006
      and -0.008 +/- 0.003 ppm (cgs) respectively, for Deltachi(do) and Deltachi(oxy) ,
      in excellent agreement with previous work by Spees et al. (Magn Reson Med
      2001;45:533-542).

PMID- 22162034
TI  - PNPLA3 (rs738409 C>G) is a common risk variant associated with hepatocellular
      carcinoma in alcoholic cirrhosis.

PMID- 22162035
TI  - Chemical etching of zinc oxide for thin-film silicon solar cells.
AB  - Chemical etching is widely applied to texture the surface of sputter-deposited
      zinc oxide for light scattering in thin-film silicon solar cells. Based on
      experimental findings from the literature and our own results we propose a model
      that explains the etching behavior of ZnO depending on the structural material
      properties and etching agent. All grain boundaries are prone to be etched to a
      certain threshold, that is defined by the deposition conditions and etching
      solution. Additionally, several approaches to modify the etching behavior through
      special preparation and etching steps are provided.

PMID- 22162036
TI  - Predicting trabecular bone elastic properties from measures of bone volume
      fraction and fabric on the basis of micromagnetic resonance images.
AB  - The relationship between fabric (a measure of structural anisotropy) and elastic
      properties of trabecular bone was examined by invoking morphology and
      homogenization theory on the basis of micromagnetic resonance images from the
      distal tibia in specimens (N = 30) and human subjects (N = 16) acquired at a 160
      * 160 * 160 MUm(3) voxel size. The fabric tensor was mapped in 7.5 * 7.5 * 7.5
      mm(3) cubic subvolumes by a three-dimensional mean-intercept-length method.
      Elastic constants (three Young's and three shear moduli) were derived from linear
      microfinite element simulations of three-dimensional grayscale bone volume
      fraction-mapped images. In the specimen data, moduli fit power laws of bone
      volume fraction (bone volume/total volume) for all three test directions and
      subvolumes (R(2) = 0.92-0.98) with exponents ranging from 1.3 to 1.8. Weaker
      linear relationships were found for the in vivo data because of a narrower range
      in bone volume/total volume. When pooling the data for all test directions and
      subvolumes, bone volume/total volume predicted elastic moduli less well in the
      specimens (mean R(2) = 0.74) and not at all in vivo. A model of bone volume/total
      volume and fabric was highly predictive of microfinite element-derived Young's
      moduli: mean R(2) s of 0.98 and 0.82 (in vivo). The results show that fabric, an
      important predictor of bone mechanical properties, can be assessed in the limited
      resolution and signal-to-noise ratio regime of micromagnetic resonance images.

PMID- 22162037
TI  - Diffusion tensor imaging of freezing of gait in patients with white matter
      changes.
AB  - BACKGROUND: Freezing of gait is a common and disabling symptom of parkinsonism.
      However, the corresponding anatomic structures have yet to be clearly elucidated.
      METHODS: We performed diffusion tensor imaging on 40 subjects with white matter
      changes. We compared apparent diffusion coefficient values and fraction
      anisotropy values of 7 candidate anatomic structures between 14 patients with
      freezing of gait (freezing of gait group) and 26 without freezing of gait
      (control group). RESULTS: Fraction anisotropy values of the bilateral
      pedunculopontine nucleus, bilateral superior premotor cortex, right orbitofrontal
      area, and left supplement motor area were significantly lower in the freezing of
      gait group than in the control group. In contrast, there were no significant
      differences in apparent diffusion coefficient values between freezing of gait and
      control groups. CONCLUSIONS: Our findings suggest that the bilateral
      pedunculopontine nucleus, bilateral superior premotor cortex, right orbitofrontal
      area, and left supplement motor area are closely related to freezing of gait.

PMID- 22162039
TI  - HpYPS1 and HpYPS7 encode functional aspartyl proteases localized at the cell
      surface in the thermotolerant methylotrophic yeast Hansenula polymorpha.
AB  - In the present study, we functionally analysed two yapsin genes of the
      thermotolerant methylotrophic yeast Hansenula polymorpha, HpYPS1 and HpYPS7, for
      their roles in maintaining cell wall integrity and proteolytic processing. Both
      HpYPS1 and HpYPS7 proteins were shown to largely localize on the cell wall via
      glycosylphosphatidylinositol anchor. Heterologous expression of HpYPS1 completely
      restored all of the growth defects of the Saccharomyces cerevisiae yps1-deletion
      strains, while HpYPS7 expression exhibited a limited complementation effect on
      the S. cerevisiae yps7-deletion strain. However, different from S. cerevisiae,
      deletion of the HpYPS genes generated only minor influence on the sensitivity to
      cell wall stress. Likewise, HpYPS1 expression was significantly induced only by a
      subset of stressor agents, such as sodium dodecyl sulphate and tunicamycin.
      HpYps1p was shown to consist of two subunits, whereas HpYps7p comprises a single
      long polypeptide chain. Biochemical analysis revealed that HpYps1p has much
      stronger proteolytic cleavage activity at basic amino acids, compared to HpYps7p.
      Consistent with the much higher proteolytic activity and expression level of
      HpYps1p compared to HpYps7p, the sole disruption of HpYPS1 was sufficient in
      eliminating the aberrant proteolytic cleavage of recombinant proteins secreted by
      H. polymorpha. The results indicate that, although their roles in the maintenance
      of cell wall integrity are not critical, HpYps1p and HpYps7p are functional
      aspartic proteases at the cell surface of H. polymorpha. Furthermore, our data
      present the high biotechnological potential of H. polymorpha yps1-mutant strains
      as hosts useful for the production of secretory recombinant proteins.

PMID- 22162040
TI  - Supramolecular electrostatic nanoassemblies for bacterial forensics.
AB  - Electrostatic nanoassemblies were employed to identify bacterial growth
      conditions. They comprise a cationic conjugated oligoelectrolyte and fluorescein
      tagged ssDNA and were optimized with a hybrid, computational neural network
      model. The photoluminescence spectra contained the oligomer and sensitized
      fluorescein emission. The spectra changed depending on the growth history of the
      bacteria introduced (see figure).

PMID- 22162041
TI  - Objective Bayes model selection in probit models.
AB  - We describe a new variable selection procedure for categorical responses where
      the candidate models are all probit regression models. The procedure uses
      objective intrinsic priors for the model parameters, which do not depend on
      tuning parameters, and ranks the models for the different subsets of covariates
      according to their model posterior probabilities. When the number of covariates
      is moderate or large, the number of potential models can be very large, and for
      those cases, we derive a new stochastic search algorithm that explores the
      potential sets of models driven by their model posterior probabilities. The
      algorithm allows the user to control the dimension of the candidate models and
      thus can handle situations when the number of covariates exceed the number of
      observations. We assess, through simulations, the performance of the procedure
      and apply the variable selector to a gene expression data set, where the response
      is whether a patient exhibits pneumonia. Software needed to run the procedures is
      available in the R package varselectIP.

PMID- 22162042
TI  - Adenoviral load diagnostics by quantitative polymerase chain reaction: techniques
      and application.
AB  - Human adenoviruses (HAdV) can cause fatal complications such as disseminated
      disease especially in a post-transplant setting. With conventional methods,
      disseminated HAdV disease could only be diagnosed with delay. Quantification of
      the HAdV load by real-time PCR in peripheral blood promised to solve this
      diagnostic dilemma. Here we review the development, applications and significance
      of quantitative HAdV PCR. The high genetic divergence of the 56 HAdV types was a
      major obstacle for developing a quantitative HAdV PCR covering all types. Several
      protocols focused either on a few, probably predominating types or tried to
      detect all known HAdV types by using a bundle of assays or a few multiplexed
      PCRs. Alternatively, generic quantitative real-time HAdV PCR protocols using
      primer and probe consensus sequences have been designed, providing considerable
      reduction of costs and hands-on time. Application of HAdV load testing by several
      studies on stem cell transplant (SCT) recipients indicated that rapidly
      increasing HAdV blood loads as well as high HAdV DNAemia (e.g. >10(4) copies/ml)
      are predictive for disseminated HAdV disease although a universal threshold value
      has not yet been established. HAdV load testing has been implemented for
      systematic screening of SCT patients permitting early diagnosis, pre-emptive
      treatment initiation and monitoring of antiviral therapy. However, further
      investigations are required to validate proposed virus load thresholds. Moreover,
      other applications of quantitative HAdV PCR, such as the diagnosis of localized
      HAdV disease, the analysis of environmental samples and monitoring of gene
      therapy with adenoviral vectors will be addressed in this review.

PMID- 22162043
TI  - p-Aminophenol-induced cytotoxicity in Jurkat T cells: protective effect of 2(RS)
      n-propylthiazolidine-4(R)-carboxylic acid.
AB  - Acetaminophen (APAP) is hepatotoxic and can cause toxicity in Jurkat T cells. p
      Aminophenol (PAP), an industrial chemical and APAP metabolite, is nephrotoxic and
      hepatotoxic. Its potential toxicity in Jurkat T cells was investigated. PAP (10
      250 uM) caused toxicity (decreased survival and increased LDH activity in
      incubation medium) and GSH depletion. At a concentration of 100 uM but not 250
      uM, PAP increased DNA fragmentation. It decreased p-Akt levels (Elisa) and at
      higher concentrations decreased p-Akt expression (Western blotting). It had no
      effect on FasL expression. The cysteine precursor 2(RS)-n-propylthiazolidine-4(R)
      carboxylic acid (250 uM) attenuated the PAP (100 uM)-induced decrease in
      viability and prevented GSH depletion and increased DNA fragmentation. It
      attenuated the PAP-induced decrease in p-Akt levels and protected against the
      decrease in p-Akt expression. The results demonstrate PAP-induced toxicity and
      suggest that it is due at least in part to apoptosis and involves GSH depletion
      and p-Akt inactivation.

PMID- 22162044
TI  - Sonoluminescence of uranyl ions in aqueous solutions.

PMID- 22162045
TI  - Tissue plasminogen activator induces microglial inflammation via a noncatalytic
      molecular mechanism involving activation of mitogen-activated protein kinases and
      Akt signaling pathways and AnnexinA2 and Galectin-1 receptors.
AB  - Inflammatory responses mediated by glial cells play a critical role in many
      pathological situations related to neurodegeneration such as Alzheimer's disease.
      Tissue plasminogen activator (tPA) is a serine protease which best-known function
      is fibrinolysis, but it is also involved in many other physiological and
      pathological events as microglial activation. Here, we found that tPA is required
      for Abeta-mediated microglial inflammatory response and tumor necrosis factor
      alpha release. We further investigated the molecular mechanism responsible for
      tPA-mediated microglial activation. We found that tPA induces a catalytic
      independent rapid and sustained activation of extracellular signal-regulated
      kinase (ERK)1/2, Jun N-terminal kinase (JNK), Akt, and p38 signaling pathways.
      Inhibition of ERK1/2 and JNK resulted in a strong inhibition of microglial
      activation, whereas Akt inhibition led to increased inflammatory response,
      suggesting specific functions for each signaling pathway in the regulation of
      microglial activation. Furthermore, we demonstrated that AnnexinA2 and Galectin-1
      receptors are involved in tPA signaling and inflammatory response in glial cells.
      This study provides new evidences supporting that tPA plays a cytokine-like role
      in glial activation by triggering receptor-mediated intracellular signaling
      circuits and opens new therapeutic strategies for the treatment of neurological
      disorders in which neuroinflammation plays a pathogenic role.

PMID- 22162046
TI  - Ripening tomato fruit after chilling storage alters protein turnover.
AB  - BACKGROUND: Tomato fruit is of prime importance owing to its qualities for human
      nutrition and its economic value. In order to extend its commercial life, it is
      harvested at mature but unripe stages and stored at low temperatures. The goal of
      this work was to study the influence of harvest and chilling storage of mature
      green tomato fruit (cv. Micro-Tom) on the protein pattern, amino acid content and
      protease activity during fruit ripening. RESULTS: Fruits were sampled during
      ripening in three different conditions: 1, on the vine; 2, off the vine; 3, off
      the vine after 4 weeks at 4  degrees C. During all fruit ripening conditions,
      protein level decreased while amino acid content increased. Chilling storage of
      mature green fruit led to a reduction in protein content. Ripening off the vine
      (conditions 2 and 3) resulted in a threefold increase in red fruit amino acid
      levels when compared with red fruit on the vine. Protease activities
      (autoproteolytic, azocaseinolytic and gelatinolytic) were detected in all fruits
      evaluated and were differently affected by ripening stage, ripening conditions
      and the presence of specific inhibitors. CONCLUSION: Harvest and chilling storage
      increased endogenous substrate proteolysis, azocaseinolytic activity and free
      amino acid levels, which could be related to fruit quality.

PMID- 22162047
TI  - DNA origami: the art of folding DNA.
AB  - The advent of DNA origami technology greatly simplified the design and
      construction of nanometer-sized DNA objects. The self-assembly of a DNA-origami
      structure is a straightforward process in which a long single-stranded scaffold
      (often from the phage M13mp18) is folded into basically any desired shape with
      the help of a multitude of short helper strands. This approach enables the ready
      generation of objects with an addressable surface area of a few thousand nm(2)
      and with a single "pixel" resolution of about 6 nm. The process is rapid, puts
      low demands on experimental conditions, and delivers target products in high
      yields. These features make DNA origami the method of choice in structural DNA
      nanotechnology when two- and three-dimensional objects are desired. This
      Minireview summarizes recent advances in the design of DNA origami
      nanostructures, which open the door to numerous exciting applications.

PMID- 22162048
TI  - Regio- and stereoselective carbobismuthination of alkynes.

PMID- 22162049
TI  - Virtual screening for compounds that mimic protein-protein interface epitopes.
AB  - Modulation of protein-protein interactions (PPI) has emerged as a new concept in
      rational drug design. Here, we present a computational protocol for identifying
      potential PPI inhibitors. Relevant regions of interfaces (epitopes) are predicted
      for three-dimensional protein models and serve as queries for virtual compound
      screening. We present a computational screening protocol that incorporates two
      different pharmacophore models. One model is based on the mathematical concept of
      autocorrelation vectors and the other utilizes fuzzy labeled graphs. In a proof
      of-concept study, we were able to identify serine protease inhibitors using a
      predicted trypsin epitope as query. Our virtual screening framework may be suited
      for rapid identification of PPI inhibitors and suggesting bioactive tool
      compounds.

PMID- 22162050
TI  - The effect of pre-hospital glycoprotein IIb-IIIa inhibitors on angiographic
      outcome in STEMI patients who are candidates for primary PCI.
AB  - OBJECTIVES: Aim of this study was to assess the effect of early initiation of
      high bolus dose tirofiban on top of dual antiplatelet therapy on angiographic
      outcome before and after primary percutaneous coronary intervention (PCI) in ST
      elevation myocardial infraction patients. BACKGROUND: Glycoprotein IIb/IIIa
      inhibitors are effective inhibitors of platelet aggregation, and have shown to
      reduce thrombotic complications in patients undergoing PCI. METHODS: This is a
      pre-specified angiographic analysis of the On-TIME 2 trial (N = 984) and its open
      label run-in phase (N = 414). All angiographic parameters, including quantitative
      coronary angiography (QCA) were performed in an independent angiographic core
      lab. RESULTS: Of the 1,398 patients, 709 patients (50.7%) were randomized to pre
      hospital tirofiban. An open infarct related vessel (TIMI 2 or 3 flow) at initial
      angiography was more often present in the tirofiban group as compared to the no
      tirofiban group (58.3% vs. 49.7%, P = 0.002). Tirofiban also reduced initial
      thrombus burden (P for trend = 0.035) as well as thrombus grade 5 (46.9% vs.
      54.3%, P = 0.016) and showed a trend toward a reduction in large thrombus burden
      (LTB) (69.4% vs. 74.5%, P = 0.055). After PCI, a trend towards a lower corrected
      TIMI frame count (cTFC) in the tirofiban group was found. A significant
      interaction was found with time of initiation of study drug, with highest
      efficacy of tirofiban when given within 76 min after symptom onset, with a
      significantly lower cTFC after PCI (21.9 +/- 17.6 vs. 23.9 +/- 18.5, P = 0.008, P
      for interaction P = 0.006). CONCLUSION: In patients undergoing primary PCI, pre
      hospital administration of tirofiban reduces initial thrombus burden and improves
      initial patency of the infarct related vessel before PCI. Initiation of tirofiban
      seems to be most effective when given very early after the onset of symptoms;
      however, this finding needs confirmation in other studies. CLINICAL TRIAL
      REGISTRATION: The On-TIME 2 trial is registered, at http://isrctn.org, number
      ISRCTN06195297.

PMID- 22162051
TI  - Atherosclerotic stroke in children? A public health red flag.

PMID- 22162052
TI  - Sleep, circadian rhythms, and dementia.

PMID- 22162053
TI  - Shift work and multiple sclerosis.

PMID- 22162054
TI  - Pharmacogenomics in neurology: current state and future steps.
AB  - In neurology, as in any other clinical specialty, there is a need to develop
      treatment strategies that allow stratification of therapies to optimize efficacy
      and minimize toxicity. Pharmacogenomics is one such method for therapy
      optimization: it aims to elucidate the relationship between human genome sequence
      variation and differential drug responses. Approaches have focused on candidate
      approaches investigating absorption-, distribution-, metabolism, and elimination
      (ADME)-related genes (pharmacokinetic pathways), and potential drug targets
      (pharmacodynamic pathways). To date, however, only few genetic variants have been
      incorporated into clinical algorithms. Unfortunately, a large number of studies
      have thrown up contradictory results due to a number of deficiencies, including
      small sample sizes, inadequate phenotyping, and genotyping strategies. Thus,
      there still exists an urgent need to establish biomarkers that could help to
      select for patients with an optimal benefit to risk relationship. Here we review
      recent advances, and limitations, in pharmacogenomics for agents used in
      neuroimmunology, neurodegenerative diseases, ischemic stroke, epilepsy, and
      primary headaches. Further work is still required in all of these areas, which
      really needs to progress on several fronts, including better standardized
      phenotyping, appropriate sample sizes through multicenter collaborations and
      judicious use of new technological advances such as genome-wide approaches, next
      generation sequencing and systems biology. In time, this is likely to lead to
      improvements in the benefit-harm balance of neurological therapies, cost
      efficiency, and identification of new drugs.

PMID- 22162055
TI  - Stem cell therapy for neonatal brain injury: perspectives and challenges.
AB  - Cerebral palsy is a major health problem caused by brain damage during pregnancy,
      delivery, or the immediate postnatal period. Perinatal stroke, intraventricular
      hemorrhage, and asphyxia are the most common causes of neonatal brain damage.
      Periventricular white matter damage (periventricular leukomalacia) is the
      predominant form in premature infants and the most common antecedent of cerebral
      palsy. Stem cell treatment has proven effective in restoring injured organs and
      tissues in animal models. The potential of stem cells for self-renewal and
      differentiation translates into substantial neuroprotection and neuroregeneration
      in the animal brain, with minimal risks of rejection and side effects. Stem cell
      treatments described to date have used neural stem cells, embryonic stem cells,
      mesenchymal stem cells, umbilical cord stem cells, and induced pluripotent stem
      cells. Most of these treatments are still experimental. In this review, we focus
      on the efficacy of stem cell therapy in animal models of cerebral palsy, and
      discuss potential implications for current and future clinical trials.

PMID- 22162056
TI  - Anti-John Cunnigham virus antibody prevalence in multiple sclerosis patients:
      baseline results of STRATIFY-1.
AB  - OBJECTIVE: A study was undertaken to define the prevalence of anti-JC virus (JCV)
      antibodies in multiple sclerosis (MS) patients and to evaluate the analytical
      false-negative rate of a 2-step anti-JC virus antibody assay. METHODS: STRATIFY-1
      is an ongoing, longitudinal, observational study of relapsing MS patients in the
      United States who are being treated or considering treatment with natalizumab.
      Baseline serum and plasma samples were collected for anti-JC virus antibody
      detection using an analytically validated, 2-step, virus-like particle-based
      enzyme-linked immunosorbent assay. Urine was collected for JC virus DNA
      detection. RESULTS: At baseline (n = 1,096), overall anti-JC virus antibody
      prevalence was 56.0% (95% confidence interval [CI], 53.0-59.0) in STRATIFY-1
      patients, with an assay false-negative rate of 2.7% (95% CI, 0.9-6.2). Prevalence
      was significantly lower in females (53.4%; 95% CI, 49.9-56.8) than males (64.3%;
      95% CI, 58.2-70.0) and increased with age, p = 0.0019 and p = 0.0001,
      respectively. Prevalence was similar in patients regardless of natalizumab
      exposure or prior immunosuppressant use, p = 0.9709 and p = 0.6632, respectively.
      STRATIFY-1 results were generally consistent with those observed in another large
      North American cohort, TYGRIS-US (n = 1,480). INTERPRETATION: Baseline results
      from STRATIFY-1 are consistent with other studies utilizing this assay that
      demonstrate a 50 to 60% prevalence of anti-JC virus antibodies, a low false
      negative rate, and an association of increasing age and male gender with
      increasing anti-JC virus antibody prevalence. Neither natalizumab exposure nor
      prior immunosuppressant use appear to affect prevalence. Longitudinal data from
      STRATIFY-1 will confirm the stability of anti-JC virus antibody prevalence over
      time.

PMID- 22162058
TI  - Role of Ninjurin-1 in the migration of myeloid cells to central nervous system
      inflammatory lesions.
AB  - OBJECTIVE: Blood-derived myeloid antigen-presenting cells (APCs) account for a
      significant proportion of the leukocytes found within lesions of multiple
      sclerosis (MS) and experimental allergic encephalomyelitis (EAE). These APCs
      along with activated microglia are thought to be pivotal in the initiation of the
      central nervous system (CNS)-targeted immune response in MS and EAE. However, the
      exact molecules that direct the migration of myeloid cells from the periphery
      across the blood-brain barrier (BBB) remain largely unknown. METHODS: We
      identified Ninjurin-1 in a proteomic screen of human BBB endothelial cells (ECs).
      We assessed the expression of Ninjurin-1 by BBB-ECs and immune cells, and we
      determined the role of Ninjurin-1 in immune cell migration to the CNS in vivo in
      EAE mice. RESULTS: Ninjurin-1 was found to be weakly expressed in the healthy
      human and mouse CNS but upregulated on BBB-ECs and on infiltrating APCs during
      the course of EAE and in active MS lesions. In human peripheral blood, Ninjurin-1
      was predominantly expressed by monocytes, whereas it was barely detectable on T
      and B lymphocytes. Moreover, Ninjurin-1 neutralization specifically abrogated the
      adhesion and migration of human monocytes across BBB-ECs, without affecting
      lymphocyte recruitment. Finally, Ninjurin-1 blockade reduced clinical disease
      activity and histopathological indices of EAE and decreased infiltration of
      macrophages, dendritic cells, and APCs into the CNS. INTERPRETATION: Our study
      uncovers an important cell-specific role for Ninjurin-1 in the transmigration of
      inflammatory APCs across the BBB and further emphasizes the importance of myeloid
      cell recruitment during the development of neuroinflammatory lesions.

PMID- 22162057
TI  - Circadian activity rhythms and risk of incident dementia and mild cognitive
      impairment in older women.
AB  - OBJECTIVE: Previous cross-sectional studies have observed alterations in activity
      rhythms in dementia patients but the direction of causation is unclear. We
      determined whether circadian activity rhythms measured in community-dwelling
      older women are prospectively associated with incident dementia or mild cognitive
      impairment (MCI). METHODS: Activity rhythm data were collected from 1,282 healthy
      community-dwelling women from the Study of Osteoporotic Fractures (SOF) cohort
      (mean age 83 years) with wrist actigraphy for a minimum of three 24-hour periods.
      Each participant completed a neuropsychological test battery and had clinical
      cognitive status (dementia, MCI, normal) adjudicated by an expert panel
      approximately 5 years later. All analyses were adjusted for demographics, body
      mass index (BMI), functional status, depression, medications, alcohol, caffeine,
      smoking, health status, and comorbidities. RESULTS: After 4.9 years of follow-up,
      195 (15%) women had developed dementia and 302 (24%) had developed MCI. Older
      women with decreased activity rhythms had a higher likelihood of developing
      dementia or MCI when comparing those in the lowest quartiles of amplitude (odds
      ratio [OR] = 1.57; 95% CI, 1.09-2.25) or rhythm robustness (OR = 1.57; 95% CI,
      1.10-2.26) to women in the highest quartiles. An increased risk of dementia or
      MCI (OR = 1.83; 95% CI, 1.29-2.61) was found for women whose timing of peak
      activity occurred later in the day (after 3:51 PM) when compared to those with
      average timing (1:34 PM-3:51 PM). INTERPRETATION: Older, healthy women with
      decreased circadian activity rhythm amplitude and robustness, and delayed rhythms
      have increased odds of developing dementia and MCI. If confirmed, future studies
      should examine whether interventions (physical activity, bright light exposure)
      that influence activity rhythms will reduce the risk of cognitive deterioration
      in the elderly.

PMID- 22162059
TI  - Multiple sclerosis normal-appearing white matter: pathology-imaging correlations.
AB  - OBJECTIVE: The study was undertaken to determine the pathologic basis of subtle
      abnormalities in magnetization transfer ratio (MTR) and diffusion tensor imaging
      (DTI) parameters observed in normal-appearing white matter (NAWM) in multiple
      sclerosis brains. METHODS: Brain tissues were obtained through a rapid postmortem
      protocol that included in situ magnetic resonance imaging (MRI). Four types of
      MRI-defined regions of interest (ROIs) were analyzed: (1) regions that were
      abnormal on all images (T2T1MTR lesions); (2) NAWM regions with slightly abnormal
      MTR located close to white matter lesions (sa-WM Close); (3) NAWM regions with
      slightly abnormal MTR located far from lesions (sa-WM Far); and (4) NAWM regions
      with normal MTR (NAWM). Immunohistochemical analysis for each ROI comprised
      immunostaining for myelin, axonal markers, activated microglia/macrophages,
      astrocytes, plasma proteins, and blood vessels. RESULTS: Forty-eight ROIs from 4
      secondary progressive MS brains were analyzed. sa-WM Close ROIs were associated
      with significantly more axonal swellings. There were more enlarged major
      histocompatibility complex II(+) microglia and macrophages detected in sa-WM Far,
      sa-WM Close, and T2T1MTR lesions than in NAWM. Across all ROIs, MTR and DTI
      measures were moderately correlated with myelin density, axonal area, and axonal
      counts. Excluding T2T1MTR lesions from analysis revealed that MTR and DTI
      measures in nonlesional white matter (WM) were correlated with activated
      microglia, but not with axonal or myelin integrity. INTERPRETATION: The
      pathologic substrates for MRI abnormalities in NAWM vary based on distance from
      focal WM lesions. Close to WM lesions, axonal pathology and microglial activation
      may explain subtle MRI changes. Distant from lesions, microglial activation
      associated with proximity to cortical lesions might underlie MRI abnormalities.

PMID- 22162060
TI  - Microinfarcts, brain atrophy, and cognitive function: the Honolulu Asia Aging
      Study Autopsy Study.
AB  - OBJECTIVE: This study was untaken to investigate the association of micro brain
      infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain
      weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic
      plaques [NPs]) mediate the association. METHODS: Subjects were 436 well
      characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain
      pathology was ascertained with standardized methods, CF was measured by the
      Cognitive Abilities Screening Instrument, and data were analyzed using formal
      mediation analyses, adjusted for age at death, time between last CF measure and
      death, education, and head size. Based on antemortem diagnoses, demented and
      nondemented subjects were examined together and separately. RESULTS: In those
      with no dementia, MBIs were strongly associated with the last antemortem CF
      score; this was significantly mediated by BW, and not NFTs or NPs. In contrast,
      among those with an antemortem diagnosis of dementia, NFTs had the strongest
      associations with BW and with CF, and MBIs were modestly associated with CF.
      INTERPRETATION: This suggests that microinfarct pathology is a significant and
      independent factor contributing to brain atrophy and cognitive impairment,
      particularly before dementia is clinically evident. The role of vascular damage
      as initiator, stimulator, or additive contributor to neurodegeneration may differ
      depending on when in the trajectory toward dementia the lesions develop.

PMID- 22162061
TI  - A gene expression phenotype in lymphocytes from Friedreich ataxia patients.
AB  - OBJECTIVE: Gene expression studies in peripheral tissues from patients with
      neurodegenerative disorders can provide insights into disease pathogenesis, and
      identify potential biomarkers, an important goal of translational research in
      neurodegeneration. Friedreich Ataxia (FRDA) is a chronic neurodegenerative
      disease caused by reduced transcription of frataxin, a ubiquitously expressed
      protein. We studied in vitro lymphocytes from FRDA patients and carriers to
      identify a peripheral gene expression phenotype. Peripheral biomarkers related to
      disease status would be extremely valuable for assessing drug efficacy and could
      provide new pathophysiological insights. METHODS: We characterized the gene
      expression profiles in peripheral blood mononuclear cells (PBMCs) from FRDA
      patients, compared with controls and related carriers. Cells were studied both
      before and after in vitro treatment with compounds that increase frataxin levels.
      Quantitative real-time polymerase chain reaction and additional microarrays were
      used to confirm a core set of genes in multiple independent series. RESULTS: We
      identified a subset of genes changed in cells from patients with pathological
      frataxin deficiency, and a core set of these genes were confirmed in independent
      series. Changes in gene expression were related to the mitochondria, lipid
      metabolism, cell cycle, and DNA repair, consistent with FRDA's known
      pathophysiology. We evaluated the in vitro effect of multiple compounds (histone
      deacetylase inhibitors) on this putative biomarker set, and found that this
      biochemical phenotype was ameliorated in accordance with drug efficacy.
      INTERPRETATION: Frataxin downregulation is associated with robust changes in gene
      expression in PBMCs, providing pathogenetic insights and a core subset of genes
      that, if verified in vivo, could be used as a peripheral biomarker.

PMID- 22162063
TI  - Epileptic networks in focal cortical dysplasia revealed using
      electroencephalography-functional magnetic resonance imaging.
AB  - OBJECTIVE: Surgical treatment of focal epilepsy in patients with focal cortical
      dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This
      may not be evident on structural magnetic resonance imaging (MRI), so
      intracranial electroencephalography (icEEG) is needed to delineate the seizure
      onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)
      related hemodynamic changes in the irritative zone (IZ). We assessed the value of
      EEG-fMRI in patients with FCD-associated focal epilepsy by examining the
      relationship between IED-related hemodynamic changes, icEEG findings, and
      postoperative outcome. METHODS: Twenty-three patients with FCD-associated focal
      epilepsy undergoing presurgical evaluation including icEEG underwent simultaneous
      EEG-fMRI at 3T. IED-related hemodynamic changes were modeled, and results were
      overlaid on coregistered T1-weighted MRI scans fused with computed tomography
      scans showing the intracranial electrodes. IED-related hemodynamic changes were
      compared with the SOZ on icEEG and postoperative outcome at 1 year. RESULTS:
      Twelve of 23 patients had IEDs during recording, and 11 of 12 had significant IED
      related hemodynamic changes. The fMRI results were concordant with the SOZ in 5
      of 11 patients, all of whom had a solitary SOZ on icEEG. Four of 5 had >50%
      reduction in seizure frequency following resective surgery. The remaining 6 of 11
      patients had widespread or discordant regions of IED-related fMRI signal change.
      Five of 6 had either a poor surgical outcome (<50% reduction in seizure
      frequency) or widespread SOZ precluding surgery. INTERPRETATION: Comparison of
      EEG-fMRI with icEEG suggests that EEG-fMRI may provide useful additional
      information about the SOZ in FCD. Widely distributed discordant regions of IED
      related hemodynamic change appear to be associated with a widespread SOZ and poor
      postsurgical outcome.

PMID- 22162062
TI  - Recovery from chronic spinal cord contusion after Nogo receptor intervention.
AB  - OBJECTIVE: Several interventions promote axonal growth and functional recovery
      when initiated shortly after central nervous system injury, including blockade of
      myelin-derived inhibitors with soluble Nogo receptor (NgR1, RTN4R) decoy protein.
      We examined the efficacy of this intervention in the much more prevalent and
      refractory condition of chronic spinal cord injury. METHODS: We eliminated the
      NgR1 pathway genetically in mice by conditional gene targeting starting 8 weeks
      after spinal hemisection injury and monitored locomotion in the open field and by
      video kinematics over the ensuing 4 months. In a separate pharmacological
      experiment, intrathecal NgR1 decoy protein administration was initiated 3 months
      after spinal cord contusion injury. Locomotion and raphespinal axon growth were
      assessed during 3 months of treatment between 4 and 6 months after contusion
      injury. RESULTS: Conditional deletion of NgR1 in the chronic state results in
      gradual improvement of motor function accompanied by increased density of
      raphespinal axons in the caudal spinal cord. In chronic rat spinal contusion,
      NgR1 decoy treatment from 4 to 6 months after injury results in 29% (10 of 35) of
      rats recovering weight-bearing status compared to 0% (0 of 29) of control rats (p
      < 0.05). Open field Basso, Beattie, and Bresnahan locomotor scores showed a
      significant improvement in the NgR-treated group relative to the control group (p
      < 0.005, repeated measures analysis of variance). An increase in raphespinal axon
      density caudal to the injury is detected in NgR1 decoy-treated animals by
      immunohistology and by positron emission tomography using a serotonin reuptake
      ligand. INTERPRETATION: Antagonizing myelin-derived inhibitors signaling with
      NgR1 decoy augments recovery from chronic spinal cord injury.

PMID- 22162064
TI  - Altered functional magnetic resonance imaging resting-state connectivity in
      periaqueductal gray networks in migraine.
AB  - OBJECTIVE: The periaqueductal gray matter (PAG), a known modulator of somatic
      pain transmission, shows evidence of interictal functional and structural
      abnormalities in migraineurs, which may contribute to hyperexcitability along
      spinal and trigeminal nociceptive pathways, and lead to the migraine attack. The
      aim of this study was to examine functional connectivity of the PAG in migraine.
      METHODS: Using resting-state functional MRI, we compared functional connectivity
      between PAG and a subset of brain areas involved in nociceptive/somatosensory
      processing and pain modulation in 17 subjects with migraine, during a pain-free
      state, versus 17 gender- and age-matched controls. We also assessed the relation
      between intrinsic resting-state correlations within PAG networks and the average
      monthly frequency of migraine attacks, as well as allodynia. RESULTS: Our
      findings show stronger connectivity between the PAG and several brain areas
      within nociceptive and somatosensory processing pathways in migraineurs versus
      controls. In addition, as the monthly frequency of migraine attacks worsens, the
      strength of the connectivity in some areas within these pathways increases,
      whereas a significant decrease in functional resting-state connectivity between
      the PAG and brain regions with a predominant role in pain modulation (prefrontal
      cortex, anterior cingulate, amygdala) can be evidenced. Finally, migraineurs with
      a history of allodynia exhibit significantly reduced connectivity between PAG,
      prefrontal regions, and anterior cingulate compared to migraineurs without
      allodynia. INTERPRETATION: These data reveal interictal dysfunctional dynamics
      within pain pathways in migraine manifested as an impairment of the descending
      pain modulatory circuits, likely leading to loss of pain inhibition, and
      hyperexcitability primarily in nociceptive areas.

PMID- 22162066
TI  - Confirmation of the extracranial site of action of sumatriptan.

PMID- 22162065
TI  - Amyloid-beta plaque growth in cognitively normal adults: longitudinal
      [11C]Pittsburgh compound B data.
AB  - Amyloid-beta (Abeta) accumulation was evaluated with 2 [(11)C]Pittsburgh compound
      B (PiB) positron emission tomography scans about 2.5 years apart in 146
      cognitively normal adults. Seventeen of 21 participants with initially elevated
      Abeta deposition demonstrated subsequent Abeta plaque growth (approximately 8.0%
      per year), and none reverted to a state of no Abeta deposits. Ten individuals
      converted from negative to positive PiB status, based on a threshold of the mean
      cortical binding potential, representing a conversion rate of 3.1% per year.
      Individuals with an epsilon4 allele of apolipoprotein E demonstrated increased
      incidence of conversion (7.0% per year). Our findings suggest that the major
      growth in Abeta burden occurs during a preclinical stage of Alzheimer disease
      (AD), prior to the onset of AD-related symptoms.

PMID- 22162068
TI  - Benefits of medical research: Hollywood weighs in.

PMID- 22162069
TI  - NerveCenter: Are federal laboratory regulations a double-edged sword?

PMID- 22162072
TI  - Linking single-molecule blinking to chromophore structure and redox potentials.
AB  - Intensity fluctuations between an ON-state and an OFF-state, also called
      blinking, are common to all luminescent objects when studied at the level of
      individuals. We studied blinking of three dyes from a homologous series (Cy3,
      Cy5, Cy7). The underlying radical anion states were induced by removing oxidants
      (i.e. oxygen) and by adding the reductant ascorbic acid. We find that for
      different conditions with distinct levels of oxidants in solution the OFF-state
      lifetime always increases in the order Cy3<Cy5<Cy7. Longer OFF-times are related
      to higher reduction potentials of the fluorophores, which increase with the size
      of the chromophore. Interestingly, we find reaction rates of the radical anion
      that are unexpectedly low at the assumed oxygen concentration. On the other hand,
      reaction rates meet the expectations of similar Rehm-Weller plots when
      methylviologen is used as oxidant, confirming the model of photoinduced reduction
      and oxidation reactions. The relation of OFF-state lifetimes to redox potentials
      might enable predictions about the nature of dark states, depending on the
      fluorophores' nano-environment in super-resolution microscopy.

PMID- 22162071
TI  - Cell-free synthesis of membrane subunits of ATP synthase in phospholipid
      bicelles: NMR shows subunit a fold similar to the protein in the cell membrane.
AB  - NMR structure determination of large membrane proteins is hampered by broad
      spectral lines, overlap, and ambiguity of signal assignment. Chemical shift and
      NOE assignment can be facilitated by amino acid selective isotope labeling in
      cell-free protein synthesis system. However, many biological detergents are
      incompatible with the cell-free synthesis, and membrane proteins often have to be
      synthesized in an insoluble form. We report cell-free synthesis of subunits a and
      c of the proton channel of Escherichia coli ATP synthase in a soluble form in a
      mixture of phosphatidylcholine derivatives. In comparison, subunit a was purified
      from the cell-free system and from the bacterial cell membranes. NMR spectra of
      both preparations were similar, indicating that our procedure for cell-free
      synthesis produces protein structurally similar to that prepared from the cell
      membranes.

PMID- 22162073
TI  - Letter to the editor. Chemical-genetic strategy for inhibiting proteasome
      function in Saccharomyces cerevisiae.

PMID- 22162074
TI  - Measuring brain oxygenation in humans using a multiparametric quantitative blood
      oxygenation level dependent MRI approach.
AB  - Quantitative blood oxygenation level dependent approaches have been designed to
      obtain quantitative oxygenation information using MRI. A mathematical model is
      usually fitted to the time signal decay of a gradient-echo and spin-echo
      measurements to derive hemodynamic parameters such as the blood oxygen saturation
      or the cerebral blood volume. Although the results in rats and human brain have
      been encouraging, recent studies have pointed out the need for independent
      estimation of one or more variables to increase the accuracy of the method. In
      this study, a multiparametric quantitative blood oxygenation level dependent
      approach is proposed. A combination of arterial spin labeling and dynamic
      susceptibility contrast methods were used to obtain quantitative estimates of
      cerebral blood volume and cerebral blood flow. These results were combined with T
      2 and T(2) measurements to derive maps of blood oxygen saturation or cerebral
      metabolic rate of oxygen. In 12 normal subjects, a mean cerebral blood volume of
      4.33 +/- 0.7%, cerebral blood flow of 43.8 +/- 5.7 mL/min/100 g, blood oxygen
      saturation of 60 +/- 6% and cerebral metabolic rate of oxygen 157 +/- 23
      MUmol/100 g/min were found, which are in agreement with literature values. The
      results obtained in this study suggest that this methodology could be applied to
      study brain hypoxia in the setting of pathology.

PMID- 22162075
TI  - Six is enough? Comparison of diffusion parameters measured using six or more
      diffusion-encoding gradient directions with deterministic tractography.
AB  - Diffusion tensor imaging tractography is commonly used to quantify white matter
      tracts in the human brain via parameters such as fractional anisotropy and mean
      diffusivity. Simulation studies recommend the use of more than six directions for
      robust parameter estimates; however, no study has examined the impact of the
      number of gradient directions on deterministic tractography-derived diffusion
      parameters in human brain. Here, for 10 major white matter tracts in 11 healthy
      volunteers at 1.5 T, six-direction diffusion tensor imaging data were compared to
      30- or 60-direction data, keeping scan time and number of b = 0 images constant
      within each test. Mean diffusivity was systematically lower for six-direction
      protocols (20/40 comparisons); six-direction data had higher fractional
      anisotropy in the superior longitudinal fasciculus and smaller tract volume for
      the genu of the corpus callosum. In general, parameter differences due to the
      number of directions were smaller than those from intersubject variation or
      signal-to-noise ratio. Despite some absolute differences, standard deviations
      were significantly different for only one of 160 comparisons. Thus, six-direction
      data provide diffusion measures with comparable robustness to 30- or 60-direction
      data and yield appropriate parameter values for most white matter tracts,
      although there are clear advantages in acquiring higher angular resolution data.

PMID- 22162076
TI  - Core structure-based design of organocatalytic [3+2]-cycloaddition reactions:
      highly efficient and stereocontrolled syntheses of 3,3'-pyrrolidonyl
      spirooxindoles.

PMID- 22162077
TI  - Applying propensity scores estimated in a full cohort to adjust for confounding
      in subgroup analyses.
AB  - BACKGROUND: A correctly specified propensity score (PS) estimated in a cohort
      ("cohort PS") should, in expectation, remain valid in a subgroup population.
      OBJECTIVE: We sought to determine whether using a cohort PS can be validly
      applied to subgroup analyses and, thus, add efficiency to studies with many
      subgroups or restricted data. METHODS: In each of three cohort studies, we
      estimated a cohort PS, defined five subgroups, and then estimated subgroup
      specific PSs. We compared difference in treatment effect estimates for subgroup
      analyses adjusted by cohort PSs versus subgroup-specific PSs. Then, over 10
      million times, we simulated a population with known characteristics of
      confounding, subgroup size, treatment interactions, and treatment effect and
      again assessed difference in point estimates. RESULTS: We observed that point
      estimates in most subgroups were substantially similar with the two methods of
      adjustment. In simulations, the effect estimates differed by a median of 3.4%
      (interquartile (IQ) range 1.3-10.0%). The IQ range exceeded 10% only in cases
      where the subgroup had < 1000 patients or few outcome events. CONCLUSIONS: Our
      empirical and simulation results indicated that using a cohort PS in subgroup
      analyses was a feasible approach, particularly in larger subgroups. Copyright (c)
      2011 John Wiley & Sons, Ltd.

PMID- 22162078
TI  - Structural and electrical characterization of a block copolymer-based unipolar
      nonvolatile memory device.
AB  - Electronic devices based on a series of synthesized block copolymers are
      demonstrated. In particular, a block copolymer system with a lamellar structure
      exhibits unipolar switching behavior. This study provides a simple strategy based
      on the adjustment of the block ratio in block copolymers to control the polymer
      morphology and thus the electrical and switching properties of polymer-based
      memory devices. 

PMID- 22162080
TI  - Parkinson's disease patients cannot get their dopamine replacement: the 8-Sinemet
      limit.

PMID- 22162081
TI  - Rhodium carbene complexes as versatile catalyst precursors for Si-H bond
      activation.
AB  - Rhodium(III) complexes comprising monoanionic C,C,C-tridentate dicarbene ligands
      activate Si-H bonds and catalyse the hydrolysis of hydrosilanes to form silanols
      and siloxanes with concomitant release of H(2). In dry MeNO(2), selective
      formation of siloxanes takes place, while changing conditions to wet THF produces
      silanols exclusively. Silyl ethers are formed when ROH is used as substrate, thus
      providing a mild route towards the protection of alcohols with H(2) as the only
      by-product. With alkynes, comparably fast hydrosilylation takes place, while
      carbonyl groups are unaffected. Further expansion of the Si-H bond activation to
      dihydrosilanes afforded silicones and polysilyl ethers. Mechanistic
      investigations using deuterated silane revealed deuterium incorporation into the
      abnormal carbene ligand and thus suggests a ligand-assisted mechanism involving
      heterolytic Si-H bond cleavage.

PMID- 22162082
TI  - Military to civilian questionnaire: a measure of postdeployment community
      reintegration difficulty among veterans using Department of Veterans Affairs
      medical care.
AB  - The primary objective of this study was to describe the development, reliability,
      and construct validity of scores on the Military to Civilian Questionnaire (M2C
      Q), a 16-item self-report measure of postdeployment community reintegration
      difficulty. We surveyed a national, stratified sample of 1,226 Iraq and
      Afghanistan veterans who used U.S. Department of Veterans Affairs (VA) medical
      care; 745 completed the M2C-Q and validated mental health screening measures. All
      analyses were based on weighted estimates. The internal consistency of the M2C-Q
      was .95 in this sample. Factor analyses indicated a single total score was the
      best-fitting model. Total scores were associated with measures theoretically
      related to reintegration difficulties including perception of overall difficulty
      readjusting back into civilian life (R(2)  = .49), probable PTSD (d = 1.07),
      probable problem drug or alcohol use (d = 0.34), and overall mental health (r = 
      .83). Subgroup analyses revealed a similar pattern of findings in those who
      screened negative for PTSD. Nonwhite and unemployed veterans reported greater
      community reintegration difficulty (d = 0.20 and 0.45, respectively). Findings
      offer preliminary support for the reliability and construct validity of M2C-Q
      scores.

PMID- 22162083
TI  - Isolation and characterisation of a kallikrein-like enzyme from Agkistrodon halys
      pallas snake venom.
AB  - BACKGROUND: Viper snake venoms contain a great variety of toxic proteins. These
      components mediate their toxicity by either stimulating or inhibiting the
      haemostatic system of human victims or experimental animals, resulting in common
      clinical complications of blood clotting or uncontrolled haemorrhage. Therefore
      it is deemed important to isolate the active component(s) from snake venom with
      kallikrein-like activity. RESULTS: A kallikrein-like proteinase of Agkistrodon
      halys pallas snake venom, designated AHP-Ka, was purified by anion exchange
      chromatography and affinity chromatography. Physicochemical studies showed that
      the purified enzyme was a 34 kDa monomeric glycoprotein, the molecular weight of
      which decreased to 26 kDa after deglycosylation with peptide N-glycosidase F
      (PNGase F). Sequence studies on the NH(2) -terminal region of the protein
      indicated that AHP-Ka shared a high degree of sequence homology with other serine
      proteinases from snake venoms. AHP-Ka showed high catalytic activity and
      kallikrein-like activity on substrates such as arginine esterase BAEE and
      chromogenic H-D-Pro-Phe-Arg-pNA.2HCl (S-2302) and was inhibited by protease
      inhibitor phenylmethylsulfonyl fluoride (PMSF). CONCLUSION: The results showed
      that AHP-Ka isolated from A. halys pallas snake venom and purified by anion
      exchange chromatography and affinity chromatography is in fact a kallikrein-like
      enzyme.

PMID- 22162084
TI  - Effect of microRNA-34a in cell cycle, differentiation, and apoptosis: a review.
AB  - The tumor suppressor gene p53 was shown to directly regulate the expression of
      microRNA-34a (miR-34a). miR-34a regulates a plethora of target proteins, which
      are involved in cell cycle, apoptosis, differentiation, and cellular
      development.miR-34a resides in the region of chromosome 1p36.23, which is
      commonly deleted in many tumor types, while it results in the loss expression of
      miR-34a. The promoters of the miR-34a gene subject to inactivation by CpG
      methylation also induce the loss expression of miR-34a. Ectopic miR-34a
      expression induces apoptosis, cell cycle arrest, and differentiation or reduces
      migration. This review summarizes the progress regarding the role of miR-34a in
      cell cycle, differentiation, and apoptosis.

PMID- 22162085
TI  - Differential genotoxicity of chemical properties and particle size of rare metal
      and metal oxide nanoparticles.
AB  - Nanoparticles of rare metal compounds are used in various products. However,
      their carcinogenicity and genotoxicity have not been sufficiently evaluated. The
      tumor-initiating and -promoting potentials of four rare metals, indium oxide
      (In2O3), dysprosium oxide (Dy2O3), tungsten oxide (WO3) and molybdenum (Mo), with
      a well-defined particle diameter were evaluated. The mutagenicity of these rare
      metals was investigated by Ames test using five bacteria strains, and
      transformability of these rare metals was investigated by cell-transformation
      assay using v-Ha-ras-transfected BALB/c 3T3 cells (Bhas 42 cells). Nano-sized
      Dy2O3 showed strong mutagenesis in all five bacteria strains tested with and
      without metabolic activation, while micro-sized particles showed weak mutagenesis
      in two bacterial strains. Dy2O3 induced transformation colonies of Bhas 42 cell
      dose-dependently, although there was no difference in the number of transformed
      foci between nano-sized and micro-sized particles. Nano-sized In2O3 and WO3
      showed positive mutagenic response in TA1537 and TA98, respectively, whereas the
      micro-sized metal oxide particles showed no mutagenesis in the test bacterial
      strains. Both nano-sized and micro-sized In2O3 showed similar levels of
      transformability. However, nano-sized and micro-sized WO3 did not show any
      transformability. Both nano-sized and micro-sized Mo particles showed neither
      mutagenesis nor transformability. These results suggest that mutagenicity of rare
      metals depends on their particle size, although transformability depends on their
      chemical components but not on their particle size.

PMID- 22162086
TI  - Enyne chlorides: substrates for copper-catalyzed asymmetric allylic alkylation.

PMID- 22162087
TI  - Dynamically tunable protein microlenses.

PMID- 22162088
TI  - Detached tip of a transseptal sheath during left atrial ablation.
AB  - Left atrial ablation has become more commonplace with the advent of catheter
      ablation for atrial fibrillation. A number of transseptal sheaths have been
      produced to enhance safe and efficient catheter manipulation in the left atrium
      (LA) for these procedures. Some of the sheaths have been subject to recall due to
      partial or complete detachment of its radiopaque tip. We report a case of a 46
      year-old female diagnosed with idiopathic dilated cardiomyopathy that presented
      with atypical left atrial flutter. During electrophysiologic study, a Swartz
      braided SL1 (SL-1) transseptal sheath was used to introduce the ablation catheter
      to the left atrium. During left atrial mapping, the radiopaque tip of the sheath
      detached from the rest of the sheath and was seen floating in the LA. After
      exchanging the SL-1 sheath with a deflectable sheath, the detached segment was
      retrieved out of the LA and eventually out of the vascular system using an
      angioplasty balloon advanced over a wire and inflated distal to the lumen of the
      detached tip. The root cause of this malfunction was found to be lack of a
      secondary bonding process that these sheaths generally undergo during the
      manufacturing process. We describe the case of a left atrial ablation procedure
      where a novel percutaneous method was able to successfully retrieve the detached
      tip of a transseptal sheath from the vascular system, thereby avoiding a
      potential catastrophic complication or thoracotomy. This method may be useful in
      other cases where similar circumstances may present.

PMID- 22162089
TI  - Multislice 1H MRSI of the human brain at 7 T using dynamic B0 and B1 shimming.
AB  - Proton MR spectroscopic imaging of the human brain at ultra-high field (>=7 T) is
      challenging due to increased radio frequency power deposition, increased magnetic
      field B(0) inhomogeneity, and increased radio frequency magnetic field
      inhomogeneity. In addition, especially for multislice sequences, these effects
      directly inhibit the potential gains of higher magnetic field and can even cause
      a reduction in data quality. However, recent developments in dynamic B(0)
      magnetic field shimming and dynamic multitransmit radio frequency control allow
      for new acquisition strategies. Therefore, in this work, slice-by-slice B(0) and
      B(1) shimming was developed to optimize both B(0) magnetic field homogeneity and
      nutation angle over a large portion of the brain. Together with a low-power water
      and lipid suppression sequence and pulse-acquire spectroscopic imaging, a
      multislice MR spectroscopic imaging sequence is shown to be feasible at 7 T. This
      now allows for multislice metabolic imaging of the human brain with high
      sensitivity and high chemical shift resolution at ultra-high field.

PMID- 22162090
TI  - VEGF-independent cell-autonomous functions of HIF-1alpha regulating oxygen
      consumption in fetal cartilage are critical for chondrocyte survival.
AB  - Fetal growth plate cartilage is nonvascularized, and chondrocytes largely develop
      in hypoxic conditions. We previously found that mice lacking the hypoxia
      inducible transcription factor HIF-1alpha in cartilage show massive death of
      centrally located, hypoxic chondrocytes. A similar phenotype was observed in mice
      with genetic ablation of either all or specifically the diffusible isoforms of
      vascular endothelial growth factor (VEGF), a prime angiogenic target of HIF
      1alpha. Here, we assessed whether VEGF is a critical downstream component of the
      HIF-1alpha-dependent survival pathway in chondrocytes. We used a genetic approach
      to conditionally overexpress VEGF164 in chondrocytes lacking HIF-1alpha,
      evaluating potential rescuing effects. The effectiveness of the strategy was
      validated by showing that transgenic expression of VEGF164 in Col2-Cre;VEGF(f/f)
      mice stimulated angiogenesis in the perichondrium, fully corrected the excessive
      hypoxia of VEGF-deficient chondrocytes, and completely prevented chondrocyte
      death. Yet, similarly crossed double-mutant embryos lacking HIF-1alpha and
      overexpressing VEGF164 in the growth plate cartilage still displayed a central
      cell death phenotype, albeit slightly delayed and less severe compared with mice
      exclusively lacking HIF-1alpha. Transgenic VEGF164 induced massive angiogenesis
      in the perichondrium, yet this only partially relieved the aberrant hypoxia
      present in HIF-1alpha-deficient cartilage and thereby likely inflicted only a
      partial rescue effect. In fact, excessive hypoxia and failure to upregulate
      phosphoglycerate-kinase 1 (PGK1), a key enzyme of anaerobic glycolytic
      metabolism, were among the earliest manifestations of HIF-1alpha deficiency in
      cartilaginous bone templates, and reduced PGK1 expression was irrespective of
      transgenic VEGF164. These findings suggest that HIF-1alpha activates VEGF
      independent cell-autonomous mechanisms to sustain oxygen levels in the challenged
      avascular cartilage by reducing oxygen consumption. Hence, regulation of the
      metabolic pathways by HIF-1alpha and VEGF-dependent regulation of angiogenesis
      coordinately act to maintain physiological cartilage oxygenation. We conclude
      that VEGF and HIF-1alpha are critical preservers of chondrocyte survival by
      ensuring an adequate balance between availability and handling of oxygen in
      developing growth cartilage.

PMID- 22162091
TI  - Ionization of methane clusters in helium nanodroplets.
AB  - The electron ionization of helium droplets doped with methane clusters is
      investigated for the first time using high-resolution mass spectrometry. The
      dominant ion products ejected into the gas phase are the unprotonated
      (CH(4))(n)(+) cluster ions along with the protonated ions, CH(5)(+)(CH(4))(n-1).
      The mass spectra show clear evidence for magic numbers, which are broadly
      consistent with icosahedral shell closings. However, unusual features were
      observed, including different magic numbers for CH(5)(+)(CH(4))(n-1) (n=55, 148)
      when compared to (CH(4))(n)(+) (n=54, 147). Possible interpretations for some of
      these differences are proposed. Products of the type [C(2)H(x)(CH(4))(n)](+),
      which result from ion-molecule chemistry, are also observed and these too show
      clear magic number features. Finally, we report the first observation of
      (CH(4))(n)(2+) dications from methane clusters. The threshold for dication
      survival occurs at n>=70 and is in good agreement with a liquid droplet model for
      fission of multiply charged ions. Furthermore, we present evidence showing that
      these dications are formed by an unusual two-step mechanism which is initiated by
      charge transfer to generate a monocation and is then followed by Penning
      ionization to generate a dication.

PMID- 22162092
TI  - Correction for arterial-tissue delay and dispersion in absolute quantitative
      cerebral perfusion DSC MR imaging.
AB  - The singular value decomposition deconvolution of cerebral tissue concentration
      time curves with the arterial input function is commonly used in dynamic
      susceptibility contrast cerebral perfusion MR imaging. However, it is sensitive
      to the time discrepancy between the arrival of the bolus in the tissue
      concentration-time curve and the arterial input function signal. This normally
      causes inaccuracy in the quantitative perfusion maps due to delay and dispersion
      effects. A comprehensive correction algorithm has been achieved through slice
      dependent time-shifting of the arterial input function, and a delay-dependent
      dispersion correction model. The correction algorithm was tested in 11 healthy
      subjects and three ischemic stroke patients scanned with a quantitative perfusion
      pulse sequence at 1.5 T. A validation study was performed on five patients with
      confirmed cerebrovascular occlusive disease scanned with MRI and positron
      emission tomography at 3.0 T. A significant effect (P < 0.05) was reported on the
      quantitative cerebral blood flow and mean transit time measurements (up to 50%).
      There was no statistically significant effect on the quantitative cerebral blood
      volume values. The in vivo results were in agreement with the simulation results,
      as well as previous literature. This minimizes the bias in patient diagnosis due
      to the existing errors and artifacts in dynamic susceptibility contrast imaging.

PMID- 22162093
TI  - Structures of dimethylsulfoniopropionate-dependent demethylase from the marine
      organism Pelagabacter ubique.
AB  - Dimethylsulfoniopropionate (DMSP) is a ubiquitous algal metabolite and common
      carbon and sulfur source for marine bacteria. DMSP is a precursor for the
      climatically active gas dimethylsulfide that is readily oxidized to sulfate,
      sulfur dioxide, methanesulfonic acid, and other products that act as cloud
      condensation nuclei. Although the environmental importance of DMSP metabolism has
      been known for some time, the enzyme responsible for DMSP demethylation by marine
      bacterioplankton, dimethylsufoniopropionate-dependent demethylase A (DmdA, EC
      2.1.1.B5), has only recently been identified and biochemically characterized. In
      this work, we report the structure for the apoenzyme DmdA from Pelagibacter
      ubique (2.1 A), as well as for DmdA co-crystals soaked with substrate DMSP (1.6
      A) or the cofactor tetrahydrofolate (THF) (1.6 A). Surprisingly, the overall fold
      of the DmdA is not similar to other enzymes that typically utilize the reduced
      form of THF and in fact is a triple domain structure similar to what has been
      observed for the glycine cleavage T protein or sarcosine oxidase. Specifically,
      while the THF binding fold appears conserved, previous biochemical studies have
      shown that all enzymes with a similar fold produce 5,10-methylene-THF, while DmdA
      catalyzes a redox-neutral methyl transfer reaction to produce 5-methyl-THF. On
      the basis of the findings presented herein and the available biochemical data, we
      outline a mechanism for a redox-neutral methyl transfer reaction that is novel to
      this conserved THF binding domain.

PMID- 22162094
TI  - A comparative study of adverse drug reactions during two heat waves that occurred
      in France in 2003 and 2006.
AB  - PURPOSE: Heat waves could reveal or aggravate several 'serious' adverse drug
      reactions (ADRs) in elderly. Thus, we wanted to describe the main characteristics
      of heat-related 'serious' ADRs occurred in patients older than 70 years during
      these two events in France (2003 and 2006). METHODS: We analysed 'serious' ADRs
      reported to the network of French pharmacovigilance centres in summer 2003 and
      2006 and suspected to be heat related. 'Serious' ADRs occurred during summers
      with heat waves (2003 and 2006) were compared with ADRs occurred during the same
      months in the summers of 2004 and 2005 (reference period). RESULTS: Patients'
      characteristics and number of 'serious' ADRs were similar whatever the year of
      the study. Number of drug-related deaths seemed higher in 2003 than in 2004-2005.
      More 'serious' heat-related ADRs were reported in the summers of 2003 and 2006
      (68 in 2003 and 72 in 2006). Comparing with the reference period, metabolic ADRs
      were less frequent during the summers of 2003 (29%, p = 0.0001) and 2006 (39%, p
      = 0.003). Occurrence of other ADRs was similar whatever the period. Drugs more
      frequently involved during heat waves were diuretics, serotonic antidepressants,
      angiotensin converting inhibitors and proton pump inhibitors. Differences between
      2003 and 2006 were found for non-dopaminergic (atropinic) antiparkinsonians or
      antiepileptics (most frequently involved in 2006) and beta-blockers or proton
      pump inhibitors (less frequently involved in 2006). CONCLUSION: The present study
      underlines the interest of a National Pharmacovigilance Database to follow each
      year the role of drugs in heat-related ADRs. This survey should be associated
      with other pharmacoepidemiological methods, such as case-control or population
      based studies.

PMID- 22162095
TI  - Chemical probing within catalyst bodies by diagonal offset Raman spectroscopy.

PMID- 22162096
TI  - Robotics as a new surgical minimally invasive approach to treatment of
      endometriosis: a systematic review.
AB  - BACKGROUND: This systematic review evaluates the role of robotics in the surgical
      treatment of endometriosis. METHODS: Electronic database searches were conducted
      in MEDLINE, Scopus, and ISI Web of Knowledge for relevant studies over the past
      10 years. RESULTS: Four published articles were found that used robotic assisted
      laparoscopy to perform endometriosis surgery. All four studies used the da Vinci
      Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA). Three studies were
      case reports, and one was a cohort study. Robotics appears to be as effective as
      conventional laparoscopy in the management of endometriosis. There were no
      reports of any major complications. CONCLUSIONS: Few studies have been published
      and show us that robotic endometriosis surgery is feasible even in severe
      endometriosis cases without conversion. There is a lack of long-term outcome
      papers in the literature. Randomized controlled trials are necessary.

PMID- 22162097
TI  - Enantioselective one-pot synthesis of alpha-amino esters by a phosphine-catalyzed
      [3+2]-cycloaddition reaction.

PMID- 22162098
TI  - Parkinson's disease motor subtypes and mood.
AB  - Parkinson's disease is heterogeneous, both in terms of motor symptoms and mood.
      Identifying associations between phenotypic variants of motor and mood subtypes
      may provide clues to understand mechanisms underlying mood disorder and symptoms
      in Parkinson's disease. A total of 513 patients were assessed using the Hospital
      Anxiety and Depression Scale, and separately classified into anxious, depressed,
      and anxious-depressed mood classes based on latent class analysis of a
      semistructured interview. Motor subtypes assessed related to age-of-onset, rate
      of progression, presence of motor fluctuations, lateralization of motor symptoms,
      tremor dominance, and the presence of postural instability and gait symptoms and
      falls. The directions of observed associations tended to support previous
      findings with the exception of lateralization of symptoms, for which there were
      no consistent or significant results. Regression models examining a range of
      motor subtypes together indicated increased risk of anxiety in patients with
      younger age-of-onset and motor fluctuations. In contrast, depression was most
      strongly related to axial motor symptoms. Different risk factors were observed
      for depressed patients with and without anxiety, suggesting heterogeneity within
      Parkinson's disease depression. Such association data may suggest possible
      underlying common risk factors for motor subtype and mood. Combined with
      convergent evidence from other sources, possible mechanisms may include
      cholinergic system damage and white matter changes contributing to non-anxious
      depression in Parkinson's disease, while situational factors related to threat
      and unpredictability may contribute to the exacerbation and maintenance of
      anxiety in susceptible individuals.

PMID- 22162099
TI  - Israeli adolescents with ongoing exposure to terrorism: suicidal ideation,
      posttraumatic stress disorder, and functional impairment.
AB  - In this study, we examined the relationships among terrorism exposure, functional
      impairment, suicidal ideation, and probable partial or full posttraumatic stress
      disorder (PTSD) from exposure to terrorism in adolescents continuously exposed to
      this threat in Israel. A convenience sample of 2,094 students, aged 12 to 18, was
      drawn from 10 Israeli secondary schools. In terms of demographic factors, older
      age was associated with increased risk for suicidal ideation, OR = 1.33, 95% CI
      [1.09, 1.62], p < .01, but was protective against probable partial or full PTSD,
      OR = 0.72, 95% CI [0.54, 0.95], p < .05; female gender was associated with
      greater likelihood of probable partial or full PTSD, OR = 1.57, 95% CI [1.02,
      2.40], p < .05. Exposure to trauma due to terrorism was associated with increased
      risk for each of the measured outcomes including probable partial or full PTSD,
      functional impairment, and suicidal ideation. When age, gender, level of exposure
      to terrorism, probable partial or full PTSD, and functional impairment were
      examined together, only terrorism exposure and functional impairment were
      associated with suicidal ideation. This study underscores the importance and
      feasibility of examining exposure to terrorism and functional impairment as risk
      factors for suicidal ideation.

PMID- 22162100
TI  - Bonding assembled colloids without loss of colloidal stability.
AB  - A facile method is demonstrated for bonding assembled colloids without loss of
      colloidal stability by thermal annealing. Examples include both close-packed and
      non-close-packed structures. The confocal microscopy image shows a cross-section
      of a 3D labyrinthine structure after it was made permanent. The 3D network is
      completely preserved after the annealing step. 

PMID- 22162101
TI  - Three-dimensional porous metal-radical frameworks based on triphenylmethyl
      radicals.
AB  - Lanthanide coordination polymers {[Ln(PTMTC)(EtOH)(2)H(2)O].x H(2)O, y EtOH}
      [Ln=Tb (1), Gd (2), and Eu (3)] and {[Ln(alphaH-PTMTC)(EtOH)(2)H(2)O].x H(2)O, y
      EtOH} [Ln=Tb (1'), Gd (2'), and Eu (3')] have been prepared by reacting Ln(III)
      ions with tricarboxylate-perchlorotriphenylmethyl/methane ligands that have a
      radical (PTMTC(3-)) or closed-shell (alphaH-PTMTC(3-)) character, respectively. X
      ray diffraction analyses reveal 3D architectures that combine helical 1D channels
      and a fairly rare (6,3) connectivity described with the
      (4(2).8).(4(4).6(2).8(5).10(4)) Schafli symbol. Such 3D architectures make these
      polymers porous solids upon departure of the non-coordinated guest-solvent
      molecules as confirmed by the XRD structure of the guest-free
      [Tb(PTMTC)(EtOH)(2)H(2)O] and [Tb(alphaH-PTMTC)(EtOH)(2)H(2)O] materials.
      Accessible voids represent 40% of the cell volume. Metal-centered luminescence
      was observed in Tb(III) and Eu(III) coordination polymers 1' and 3', although the
      Ln(III)-ion luminescence was quenched when radical ligands were involved. The
      magnetic properties of all these compounds were investigated, and the nature of
      the {Ln-radical} (in 1 and 2) and the {radical-radical} exchange interactions (in
      3) were assessed by comparing the behaviors for the radical-based coordination
      polymers 1-3 with those of the compounds with the diamagnetic ligand set. Whilst
      antiferromagnetic {radical-radical} interactions were found in 3, ferromagnetic
      {Ln-radical} interactions propagated in the 3D architectures of 1 and 2.

PMID- 22162102
TI  - A novel technique for renal stenting in the setting of type-B aortic dissection.
AB  - A type-B acute aortic dissection patient required renal artery revascularization
      for renal artery stenosis resulting from the compression by a false lumen. Renal
      artery stenting was complicated by unclear opacification of the ostia resulting
      from the collapsed true lumen of both renal artery and aorta. The use of the
      "Szabo" technique facilitated this procedure by allowing us to position the stent
      edge precisely at the ostium. This is the first report of this technique utilized
      in this lesion subset.

PMID- 22162103
TI  - High-spin square-planar Co(II) and Fe(II) complexes and reasons for their
      electronic structure.

PMID- 22162104
TI  - Agronomical factors influencing the legumin/vicilin ratio in pea (Pisum sativum
      L.) seeds.
AB  - BACKGROUND: Many research studies have investigated the impact of agronomical
      factors on the protein content of pea (Pisum sativum). This study aimed to
      establish if a correlation exists between protein content and legumin/vicilin
      (L/V) ratio in pea seeds and to identify agronomical factors that have an impact
      on this ratio. RESULTS: The L/V ratio was positively correlated with protein
      content (r = 0.58, P <= 0.01), but no linear regression was applicable (adjusted
      R(2) = 0.31). Both variety and cultivation year had a highly significant effect
      on the ratio (P < 0.001). The interaction between these two factors was also
      highly significant (P < 0.001), some varieties being less sensitive to climatic
      conditions than others. Cultivation location had a highly significant effect (P <
      0.01). There was no interaction between variety and location. Seeding density had
      a highly significant effect on the ratio (P < 0.01), with a saturation effect
      above 60 seeds m(-2). CONCLUSION: Further studies should establish if a linear
      regression model can be applied to pea varieties independently. Varieties with a
      stable L/V ratio can prove to be useful in the food industry. Other agronomical
      factors (soil type and seeding density) should be considered for the production
      of pea seeds with a specific L/V ratio.

PMID- 22162106
TI  - An efficient and exact approach for detecting trends with binary endpoints.
AB  - Lloyd (Aust. Nz. J. Stat., 50, 329-345, 2008) developed an exact testing approach
      to control for nuisance parameters, which was shown to be advantageous in testing
      for differences between two population proportions. We utilized this approach to
      obtain unconditional tests for trends in 2 * K contingency tables. We compare the
      unconditional procedure with other unconditional and conditional approaches based
      on the well-known Cochran-Armitage test statistic. We give an example to
      illustrate the approach, and provide a comparison between the methods with
      regards to type I error and power. The proposed procedure is preferable because
      it is less conservative and has superior power properties.

PMID- 22162107
TI  - Challenging evidence-based decision-making: a hypothetical case study about
      return to work.
AB  - A hypothetical case study about return to work was used to explore the process of
      translating research into practice. The method involved constructing a case study
      derived from the characteristics of a typical, sick-listed employee with non
      specific low back pain in Norway. Next, the five-step evidence-based process,
      including the Patient, Intervention, Co-Interventions and Outcome framework
      (PICO), was applied to the case study. An inductive analysis produced 10
      technical and more fundamental challenges to incorporate research into
      intervention decisions for an individual with comorbidity. A more dynamic,
      interactive approach to the evidence-based practice process is proposed. It is
      recommended that this plus the 10 challenges are validated with real life cases,
      as the hypothetical case study may not be replicable.

PMID- 22162108
TI  - The protein synthesis inhibitors mycalamides A and E have limited susceptibility
      toward the drug efflux network.
AB  - The mycalamides belong to a family of protein synthesis inhibitors noted for
      antifungal, antitumour, antiviral, immunosuppressive, and nematocidal activities.
      Here we report a systematic analysis of the role of drug efflux pumps in
      mycalamide resistance and the first isolation of mycalamide E. In human cell
      lines, neither P-glycoprotein overexpression nor the use of efflux pump
      inhibitors significantly modulated mycalamide A toxicity in the systems tested.
      In Saccharomyces cerevisiae, it appears that mycalamide A is subject to efflux by
      the principle mediator of xenobiotic efflux, Pdr5p along with the major
      facilitator superfamily pump Tpo1p. Mycalamide E showed a similar efflux profile.
      These results suggest that future drugs based on the mycalamides are likely to be
      valuable in situations where efflux pump-based resistance leads to failure of
      other chemotherapeutic approaches, although efflux may be a mediator of
      resistance in antifungal applications.

PMID- 22162109
TI  - Molecular recognition at the active site of factor Xa: cation-pi interactions,
      stacking on planar peptide surfaces, and replacement of structural water.
AB  - Factor Xa, a serine protease from the blood coagulation cascade, is an ideal
      enzyme for molecular recognition studies, as its active site is highly shape
      persistent and features distinct, concave sub-pockets. We developed a family of
      non-peptidic, small-molecule inhibitors with a central tricyclic core orienting a
      neutral heterocyclic substituent into the S1 pocket and a quaternary ammonium ion
      into the aromatic box in the S4 pocket. The substituents were systematically
      varied to investigate cation-pi interactions in the S4 pocket, optimal
      heterocyclic stacking on the flat peptide walls lining the S1 pocket, and
      potential water replacements in both the S1 and the S4 pockets. Structure
      activity relationships were established to reveal and quantify contributions to
      the binding free enthalpy, resulting from single-atom replacements or positional
      changes in the ligands. A series of high-affinity ligands with inhibitory
      constants down to K(i)=2 nM were obtained and their proposed binding geometries
      confirmed by X-ray co-crystal structures of protein-ligand complexes.

PMID- 22162110
TI  - Effects of four types of hydroxyapatite nanoparticles with different nanocrystal
      morphologies and sizes on apoptosis in rat osteoblasts.
AB  - Hydroxyapatite nanoparticles (nano-HAP) have been reported to cause inflammatory
      reactions. Here, we aimed to compare the effects of four types of nano-HAP with
      different nanocrystal morphologies (short rod-like, long rod-like, spherical or
      needle-shaped crystals) and sizes (10-20, 10-30 or 20-40 nm) on growth inhibition
      and apoptosis in primary cultured rat osteoblasts. The osteoblasts was treated
      with the four types of nano-HAP at various concentrations (20, 40, 60, 80 or 100
      mg l-1). The nano-HAP specific surface area was detected using the Brunauer,
      Emmet and Teller method. The cell growth rate was detected using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; apoptotic
      alterations and the level of reactive oxygen species in osteoblasts were measured
      using flow cytometry; and the amounts of apoptotic p53 and cytochrome c proteins
      were measured using western blotting. We observed that all four types of nano-HAP
      inhibited the growth of osteoblasts in a dose-dependent manner. These nano-HAP
      significantly induced apoptosis in osteoblasts. Nano-HAP with smaller specific
      surface areas induced lower apoptosis rates. The needle-shaped and the short rod
      like particles induced greater cellular injury than the spherical and long rod
      like particles, respectively. The increased apoptosis rates were accompanied by
      increased p53 and cytochrome c expression. These findings indicate that nano-HAP
      inhibit the activity of osteoblasts and also induce the apoptosis of osteoblasts
      in vitro. These findings also suggest that the nano-HAP-induced apoptotic pathway
      is mediated by a mitochondrial-dependent pathway. Moreover, the sizes,
      morphologies and concentrations of nano-HAP have significant effects on the
      apoptotic level.

PMID- 22162111
TI  - Transition-metal-free direct arylation of anilines.

PMID- 22162112
TI  - WNT5A is induced by inflammatory mediators in bone marrow stromal cells and
      regulates cytokine and chemokine production.
AB  - WNT5A has recently been implicated in inflammatory processes, but its role as a
      bone marrow stromal cell (BMSC)-derived mediator of joint inflammation in
      arthritis is unclear. Here, we investigated whether inflammatory stimuli induce
      WNT5A in BMSC to control inflammatory responses. WNT5A levels were determined in
      human BMSC after stimulation with lipopolysaccharide (LPS) or tumor necrosis
      factor alpha (TNF-alpha,) and in synovial cells and tissue of patients with
      rheumatoid arthritis (RA) and human TNF-alpha transgenic (hTNFtg) mice. A
      microarray analysis of WNT5A-treated murine osteoblasts was performed using
      Affymetrix gene chips. The regulation of cytokine/chemokine expression was
      confirmed by qPCR, ELISA, and Luminex technology in BMSC after stimulation with
      WNT5A or WNT5A knockdown. Relevant signaling pathways were identified using
      specific inhibitors. Migration of MACS-purified T lymphocytes and monocytes was
      assessed using the FluoroBlok system. WNT5A expression was increased threefold in
      BMSC after stimulation with LPS or TNF-alpha. Synovial fibroblasts from patients
      with RA showed a twofold increase of WNT5A expression compared with control
      cells, and its expression was highly induced in the synovial tissue of patients
      with RA and hTNFtg mice. Microarray analysis of WNT5A-treated osteoblasts
      identified cytokines and chemokines as targets. The induction of IL-1beta, IL-6,
      CCL2, CCL5, CXCL1, and CXCL5 by WNT5A was confirmed in BMSC and depended on the
      activation of the NF-kappaB, mitogen-activated protein (MAPK), and Akt pathways.
      Accordingly, knockdown of WNT5A markedly reduced the basal and LPS-induced
      cytokine/chemokine production. Finally, migration of monocytes and T cells toward
      the supernatant of WNT5A-treated BMSC was increased by 25% and 20%, respectively.
      This study underlines the critical role of BMSC-derived WNT5A in the regulation
      of inflammatory processes and suggests its participation in the pathogenesis of
      RA.

PMID- 22162113
TI  - Understanding heterogeneity in price elasticities in the demand for alcohol for
      older individuals.
AB  - This paper estimates the price elasticity of demand for alcohol using Health and
      Retirement Study data. To account for unobserved heterogeneity in price
      responsiveness, we use finite mixture models. We recover two latent groups, one
      is significantly responsive to price, but the other is unresponsive. The group
      with greater responsiveness is disadvantaged in multiple domains, including
      health, financial resources, education and perhaps even planning abilities. These
      results have policy implications. The unresponsive group drinks more heavily,
      suggesting that a higher tax would fail to curb the negative alcohol-related
      externalities. In contrast, the more disadvantaged group is more responsive to
      price, thus suffering greater deadweight loss, yet this group consumes fewer
      drinks per day and might be less likely to impose negative externalities.

PMID- 22162114
TI  - Biexponential diffusion decay in formalin-fixed prostate tissue: preliminary
      findings.
AB  - Magnetic resonance microimaging was used to measure diffusion decay over an
      extended b-factor range in a formalin-fixed normal prostate sample and a Gleason
      pattern 3+4 cancer tissue sample. The coefficients of biexponential fits to
      diffusion decay data from 1600 voxels of dimension 160 * 160 * 160 MUm(3) in each
      sample were correlated with underlying epithelial and stromal compartment partial
      volumes estimated from high-resolution apparent diffusion coefficient (ADC) data
      (40 * 40 * 40 MUm(3) voxels) from the same tissue. In the normal tissue sample,
      the signal fractions of the low and high ADC components of the biexponential fits
      correlated linearly with partial volumes of epithelial tissue (R(2) = 0.6) and
      stromal tissue (R(2) = 0.5), respectively. Similar but weaker correlations were
      observed in the cancer sample. Epithelium-containing high spatial resolution
      voxels appeared to be composed of ~60% low ADC and ~40% high ADC component.
      Stromal voxels appeared to be composed of ~20% low ADC and ~80% high ADC
      component. This preliminary report suggests that distinctly different diffusion
      properties in microscopically adjacent cell types contribute to the
      multiexponential diffusion decay phenomenon in prostate tissue.

PMID- 22162116
TI  - SiO(2)-surface-assisted controllable synthesis of TaON and Ta3N5 nanoparticles
      for alkene epoxidation.

PMID- 22162115
TI  - Evaluation of periodic limb movements in a putative animal model of restless leg
      syndrome.
AB  - Restless leg syndrome (RLS) is a major healthcare burden with increasing
      prevalence. It has been demonstrated that periodic limb movements (PLM) can occur
      as an isolated phenomenon, but they are often associated with this syndrome and
      are the only symptom of this disorder that can be measured
      electrophysiologically. The aim of this study was to examine the sleep-wake
      behavior and the presence of limb movement in a rat model of RLS induced by
      lesioning the A11 dopaminergic nuclei with the neurotoxin 6-hydroxydopamine (6
      OHDA). Rats were implanted with electrodes for electrocorticography and
      electromyography. Sleep recordings were monitored during light/dark periods
      lasting 12 hours each and were evaluated on days 7, 15, and 28 after injection of
      the drug or phosphate-buffered saline (PBS). A control group that did not receive
      any injection was also included. Wakefulness percentages were generated for 4
      hour segments of the dark period, yielding the following 3 bins: 7 PM to 11 PM,
      11 PM to 3 AM, and 3 PM to 7 PM. Additionally, slow wave sleep, paradoxical
      sleep, wakefulness, and limb movements were evaluated over the entire 12 hours of
      the light/dark cycle. All A11-lesioned rats exhibited an increased percentage of
      wakefulness during the last block of the dark period, as would be expected for an
      animal model of this syndrome. In addition, at all time points after lesioning,
      these animals presented increased frequencies of limb movement during both the
      light and the dark periods. These alterations were reversed by the acute
      administration of the dopaminergic agonist pramipexole. This animal model
      strengthens the notion that 6-OHDA-induced A11 lesions can be a valid animal
      model for RLS and PLM.

PMID- 22162117
TI  - Do patients with type 2 diabetes mellitus have an increased prevalence of
      Cushing's syndrome?
AB  - Many clinical features are common for patients with type 2 diabetes mellitus
      (T2DM) and Cushing's syndrome (CS) such as central obesity, hypertension and
      dyslipidaemia. Patients with CS often have T2DM. Because T2DM is much more
      frequent than CS, it is possible that some patients with T2DM have increased
      production of cortisol and thus represent patients with CS. The aim of this
      review was to evaluate the prevalence of CS in patients with T2DM. A search was
      performed in PubMed and Medline. We found seven prospective studies, two case
      control studies and two cross-sectional studies. The difficulties in diagnosing
      subclinical CS is discussed. The most frequent tests for diagnosing CS, late
      night salivary cortisol, 1-mg dexamethasone suppression test and urinary free
      cortisol are discussed and put in relation to the results of the literature
      found. The observed prevalence of CS in patients with T2DM varies widely between
      the different studies, ranging from 0-9.4%. This may be due to patient selection,
      differences in test methodology (including choice of test), cutoff values and
      different cortisol assays. The true prevalence of CS in T2DM has not been
      determined. We need more studies investigating the prevalence of CS in T2DM
      patients. There is a need for developing more specific tests for diagnosing CS in
      patients with only slightly elevated cortisol secretion and subclinical CS. We
      suggest that examination for hypercortisolism should only be performed in T2DM
      patients with a cushingoid appearance and hypertension or truncal obesity or
      dyslipidaemia.

PMID- 22162118
TI  - Increase in SNR for 31P MR spectroscopy by combining polarization transfer with a
      direct detection sequence.
AB  - The sensitivity of (31)P MRS can be increased using higher magnetic fields, but
      also by using (1)H to (31)P polarization transfer techniques where the
      sensitivity is determined by the polarization of the proton spins and thus the
      signal-to-noise per unit time is unaffected by the slow T(1) relaxation
      properties of the (31)P spins. This implies that (31)P spins can be manipulated
      during the T(1) relaxation of the (1)H spins without affecting the signal-to
      noise of the (1)H to (31)P polarization transferred spins. It is shown here that
      by combining (1)H to (31)P polarization transfer with a direct (31)P detection
      sequence in one repetition time, one can gain more signal-to-noise per unit of
      time as compared to a polarization transfer sequence alone. Proof of principle
      was demonstrated by phantom measurements and additionally the method was applied
      to the human calf muscle and to the human breast in vivo at 7 T.

PMID- 22162119
TI  - RASER angioplasty.
AB  - The experience with a new approach of using combined debulking technique for
      treating heavily calcified coronary artery lesions with both LASER and high speed
      rotational atherectomy, which is being labeled as RASER PCI, is described. The
      RASER PCI approach has been used in three different patients with severely
      calcified, undilatable coronary artery lesions that were unresponsive to either
      technique alone, with successful and satisfactory outcome.

PMID- 22162120
TI  - Galen's "anastomosis" revisited.
AB  - This study aimed to examine the incidence and contribution to the innervation of
      the larynx from Galen's "Anastomosis" (GA), which is the direct connection
      between the dorsal branches of the internal laryngeal nerve (ILN) and the
      recurrent laryngeal nerve (RLN). Fifty adult laryngeal specimens were micro
      dissected. The diameter of the ILN and RLN were measured immediately after each
      had given off their muscular branches to form GA. The incidence of GA was 81%.
      The average diameter of the ILN after giving off muscular branches to form GA was
      1.28 mm (right) and 1.27 mm (left) while the average diameter of the RLN after
      giving off muscular branches to form GA was 0.65 mm (right) and 0.68 mm (left).
      The weighted mean incidence of GA (77.3%) calculated from a review of the
      literature concurred with the present finding of 81%. The ILN and RLN supplied
      the laryngeal musculature. According to the results obtained; it appears that the
      ILN may provide a greater contribution to the connection between the ILN and RLN
      as the morphometric contribution from the ILN was larger in comparison to the
      RLN. In addition, the authors propose a suitable term viz. the "communicating
      branch" as opposed to the commonly used misnomer GA to describe the connection
      between the dorsal branch of the RLN and the ILN, based on the definition that an
      "Anastomosis" refers to blood vessels and that a single connection exists between
      the dorsal branch of the RLN and ILN.

PMID- 22162121
TI  - Environmental Toxicology and Chemistry: thirty years later.

PMID- 22162122
TI  - Paradigms to assess the environmental impact of manufactured nanomaterials.

PMID- 22162123
TI  - The bivalency effect in task switching: event-related potentials.
AB  - During task switching, if we occasionally encounter stimuli that cue more than
      one task (i.e., bivalent stimuli), response slowing is observed on all univalent
      trials within that block, even when no features overlap with the bivalent
      stimuli. This observation is known as the bivalency effect. Previous fMRI work
      (Woodward et al., 2008) clearly suggests a role for the dorsal anterior cingulate
      cortex (dACC) in the bivalency effect, but the time course remains uncertain.
      Here, we present the first high-temporal resolution account for the bivalency
      effect using stimulus-locked event-related potentials. Participants alternated
      among three simple tasks in six experimental blocks, with bivalent stimuli
      appearing occasionally in bivalent blocks (blocks 2, 4, and 6). The increased
      reaction times for univalent stimuli in bivalent blocks demonstrate that these
      stimuli are being processed differently from univalent stimuli in purely
      univalent blocks. Frontal electrode sites captured significant amplitude
      differences associated with the bivalency effect within time windows 100-120 ms,
      375-450 ms, and 500-550 ms, which may reflect additional extraction of visual
      features present in bivalent stimuli (100-120 ms) and suppression of processing
      carried over from irrelevant cues (375-450 ms and 500-550 ms). Our results
      support the fMRI findings and provide additional evidence for involvement of the
      dACC. Furthermore, the bivalency effect dissipated with extended practice both
      behaviorally and electrophysiologically. These findings are discussed in relation
      to the differential processing involved in a controlled response style.

PMID- 22162124
TI  - Effects of matrine on proliferation and apoptosis in gallbladder carcinoma cells
      (GBC-SD).
AB  - Although matrine, a primary active component of dried Sophora flavescens root (ku
      shen), is known to induce apoptosis in a variety of tumor cells in vitro, the
      molecular mechanism of such apoptosis remains elusive. This analysis of the cell
      cycle and apoptosis in matrine-treated human gallbladder carcinoma cells (GBC-SD)
      showed that matrine can indeed inhibit cell proliferation and induce G1 cell
      cycle arrest and apoptosis in a dose- and time-dependent manner. An additional
      western blot analysis of matrine-treated cells also showed caspase-3 and Bcl-2
      activation, as well as cyclinE down-regulation. Overall, the results indicate
      that matrine perturbs gallbladder cancer cell progression during the G1 phase by
      down-regulating cyclinE and induces apoptosis by decreasing the expression of the
      antiapoptotic protein Bcl-2 and increasing expression of the proapoptotic protein
      Bax.

PMID- 22162125
TI  - Fluorinated metal-organic frameworks: advantageous for higher H2 and CO2
      adsorption or not?
AB  - The synthesis, structure, and gas adsorption properties of three new metal
      organic frameworks (MOFs) designed from isonicotinic acid (INA) and its
      fluorinated analogue 3-fluoroisonicotinic acid (FINA) along with Co(II) as the
      metal center have been reported. Co-INA-1
      ([Co(3)(INA)(4)(O)(C(2)H(5)OH)(3)][NO(3)].C(2)H(5)OH.3H(2)O; INA=isonicotinic
      acid) and Co-INA-2 ([Co(INA)(2)].DMF) are structural isomers as are Co-FINA-1
      ([Co(3-)(FINA)(4)(O)(C(2) H(5) OH)(2)].H(2)O; FINA=3-fluoroisonicotinic acid) and
      Co-FINA-2 ([Co(FINA)(2)].H(2)O), but the most important thing to note here is
      that Co-INA-1 and Co-FINA-1 are isostructural as are Co-INA-2 and Co-FINA-2. The
      effect of partial introduction of fluorine atoms into the framework on the gas
      uptake properties of MOFs having similar structures has been analyzed
      experimentally and computationally in isostructural MOFs.

PMID- 22162127
TI  - Estimation and testing of the relative risk of disease in case-control studies
      with a set of k matched controls per case with known prevalence of disease.
AB  - The analysis of case-control studies with matched controls per case is well
      documented in the medical literature. Of primary interest is the estimation of
      the relative risk of disease. Matched case-control studies fall into two
      scenarios: the probability of exposure is constant within each of the case and
      control groups, or the probability of exposure varies within each group. Numerous
      estimation procedures have been developed for both scenarios. Often these
      procedures are developed under the rare disease assumption, where the relative
      risk of disease is approximated by the odds ratio. In this paper, without making
      the rare disease assumption, we develop consistent estimators of the relative
      risk of disease for both scenarios. Exact derivations of the relative risk of
      disease are provided. Estimators, confidence intervals, and test statistics for
      the relative risk of disease are developed. We then make the following
      observations based on extensive simulations. First, our estimators are as close
      or closer to the relative risk of disease than other estimators. Second, our
      estimators produce mean square errors for the relative risk of disease that are
      as good as or better than these other estimators. Third, our confidence intervals
      provide accurate coverage probabilities. Therefore, these new estimators,
      confidence intervals, and test statistics can be used to either estimate or test
      the relative risk of disease in matched case-control studies.

PMID- 22162128
TI  - Protective effect of selenium against mercury-induced toxicity on hematological
      and biochemical parameters of Oreochromis niloticus.
AB  - In this study, to identify mercury (Hg) toxicity and whether selenium (Se) has
      any role in alleviation of this toxicity, it was investigated the changes in
      hematological and serum biochemical parameters of Oreochromis niloticus. Fish
      were exposed to 0.01 and 0.1 mg/L Hg and 0.01 mg/L Hg + 0.1 mg/L Se and 0.1 mg/L
      Hg + 1.0 mg/L Se for 7 and 14 days. The exposure of O. niloticus to Hg alone
      resulted in decreases in red blood cell, white blood cell, hemoglobin, hematocrit
      values, and cholinesterase activity while it increased in alanine
      aminotransferase and aspartate aminotransferase activities and cortisol and
      glucose levels. Se, in combination with Hg, partially or totally caused an
      alleviation for the toxic effect of Hg on the above mentioned hematological and
      biochemical parameters. The results of our study showed that Se has a protective
      effect against toxicity induced by Hg.

PMID- 22162129
TI  - A generic platform for the addressable functionalisation of electrode surfaces
      through self-induced "electroclick".
AB  - A novel and general strategy for the immobilisation of functional objects onto
      electrodes is described. The concept is based on the addition of two pendant
      ethynyl groups onto a bis(pyridyl)amine derivative, which acts as a molecular
      platform. This platform is pre-functionalised with an N(3)-tagged object of
      interest by Huisgen cycloaddition to one of the ethynyl groups in biphasic
      conditions. Hence, when complexed by Cu(II) , this molecular-object holder can be
      immobilised, by a "self-induced electroclick", through the second ethynyl group
      onto N(3)-alkanethiol self-assembled monolayers on a gold electrode. Two
      different functional groups, a redox innocent ((CH(2))(3)-Ph) and an
      electrochemical probe (ferrocene), were immobilised by following this strategy.
      The in situ electrochemical grafting showed, for both systems, that the kinetics
      of immobilisation is fast. The voltammetric characterisation of the surface
      tagged functionalised copper complexes indicated that a good surface coverage was
      achieved and that a moderately fast electron-transfer reaction occurs.
      Remarkably, in the case of the redox-active ferrocenyl-immobilised system, the
      electrochemical response highlighted the involvement of the copper ion of the
      platform in the kinetics of the electron transfer to the ferrocene moiety. This
      platform is a promising candidate for applications in surface addressing in areas
      as diverse as biology and materials.

PMID- 22162130
TI  - Xenopus staufen2 is required for anterior endodermal organ formation.
AB  - Defining the regulatory molecular networks involved in patterning the developing
      anterior endoderm is essential to understand how the pancreas, liver, stomach,
      and duodenum are discretely specified from each other. In this study, we analyzed
      the expression and function of the double-stranded RNA-binding protein Staufen2
      in Xenopus laevis endoderm. We found that staufen2 was broadly expressed within
      the developing endoderm beginning at gastrulation becoming localized to the
      anterior endoderm at later stages. Through morpholino-mediated knockdown, we
      demonstrate that Staufen2 function is required for proper formation of the
      stomach, liver, and pancreas. We define that its function is required during
      gastrulation for proper patterning of the dorsal-ventral axis and that it acts to
      regulate expression of BMP signaling components.

PMID- 22162131
TI  - Michael Overholtzer: answering existential questions on entosis.

PMID- 22162132
TI  - Lipid traffic: Osh4p makes an unexpected exchange.
AB  - A new study in this issue (De Saint-Jean et al. 2011. J. Cell Biol.
      http://dx.doi.org/jcb.201104062) reveals that the sterol transfer protein Osh4p
      can also transport the signaling phospholipid phosphatidylinositol 4-phosphate
      (PI(4)P), which binds to the same site in Osh4p as sterol. This finding helps
      explain some previously published studies and also indicates that lipid/sterol
      exchange could contribute to establishing a sterol gradient in cells.

PMID- 22162133
TI  - Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid
      bilayers.
AB  - Osh/Orp proteins transport sterols between organelles and are involved in
      phosphoinositide metabolism. The link between these two aspects remains elusive.
      Using novel assays, we address the influence of membrane composition on the
      ability of Osh4p/Kes1p to extract, deliver, or transport dehydroergosterol (DHE).
      Surprisingly, phosphatidylinositol 4-phosphate (PI(4)P) specifically inhibited
      DHE extraction because PI(4)P was itself efficiently extracted by Osh4p. We solve
      the structure of the Osh4p-PI(4)P complex and reveal how Osh4p selectively
      substitutes PI(4)P for sterol. Last, we show that Osh4p quickly exchanges DHE for
      PI(4)P and, thereby, can transport these two lipids between membranes along
      opposite routes. These results suggest a model in which Osh4p transports sterol
      from the ER to late compartments pinpointed by PI(4)P and, in turn, transports
      PI(4)P backward. Coupled to PI(4)P metabolism, this transport cycle would create
      sterol gradients. Because the residues that recognize PI(4)P are conserved in
      Osh4p homologues, other Osh/Orp are potential sterol/phosphoinositol phosphate
      exchangers.

PMID- 22162134
TI  - Synergy between the ESCRT-III complex and Deltex defines a ligand-independent
      Notch signal.
AB  - The Notch signaling pathway defines a conserved mechanism that regulates cell
      fate decisions in metazoans. Signaling is modulated by a broad and multifaceted
      genetic circuitry, including members of the endocytic machinery. Several
      individual steps in the endocytic pathway have been linked to the positive or
      negative regulation of the Notch receptor. In seeking genetic elements involved
      in regulating the endosomal/lysosomal degradation of Notch, mediated by the
      molecular synergy between the ubiquitin ligase Deltex and Kurtz, the nonvisual
      beta-arrestin in Drosophila, we identified Shrub, a core component of the ESCRT
      III complex as a key modulator of this synergy. Shrub promotes the lysosomal
      degradation of the receptor by mediating its delivery into multivesicular bodies
      (MVBs). However, the interplay between Deltex, Kurtz, and Shrub can bypass this
      path, leading to the activation of the receptor. Our analysis shows that Shrub
      plays a pivotal rate-limiting step in late endosomal ligand-independent Notch
      activation, depending on the Deltex-dependent ubiquitinylation state of the
      receptor. This activation mode of the receptor emphasizes the complexity of Notch
      signal modulation in a cell and has significant implications for both development
      and disease.

PMID- 22162135
TI  - Distinct intracellular motifs of Delta mediate its ubiquitylation and activation
      by Mindbomb1 and Neuralized.
AB  - DSL proteins are transmembrane ligands of the Notch receptor. They associate with
      a RING (really interesting new gene) family E3 ubiquitin ligase, either
      Neuralized (Neur) or Mindbomb 1 (Mib1), as a prerequisite to signaling. Although
      Neur and Mib1 stimulate internalization of DSL ligands, it is not known how
      ubiquitylation contributes to signaling. We present a molecular dissection of the
      intracellular domain (ICD) of Drosophila melanogaster Delta (Dl), a prototype DSL
      protein. Using a cell-based assay, we detected ubiquitylation of Dl by both Neur
      and Mib1. The two enzymes use distinct docking sites and displayed different
      acceptor lysine preferences on the Dl ICD. We generated Dl variants that
      selectively perturb its interactions with Neur or Mib1 and analyzed their
      signaling activity in two in vivo contexts. We found an excellent correlation
      between the ability to undergo ubiquitylation and signaling. Therefore,
      ubiquitylation of the DSL ICD seems to be a necessary step in the activation of
      Notch.

PMID- 22162136
TI  - Live imaging of apoptosis in a novel transgenic mouse highlights its role in
      neural tube closure.
AB  - Many cells die during development, tissue homeostasis, and disease. Dysregulation
      of apoptosis leads to cranial neural tube closure (NTC) defects like exencephaly,
      although the mechanism is unclear. Observing cells undergoing apoptosis in a
      living context could help elucidate their origin, behavior, and influence on
      surrounding tissues, but few tools are available for this purpose, especially in
      mammals. In this paper, we used insulator sequences to generate a transgenic
      mouse that stably expressed a genetically encoded fluorescence resonance energy
      transfer (FRET)-based fluorescent reporter for caspase activation and performed
      simultaneous time-lapse imaging of apoptosis and morphogenesis in living embryos.
      Live FRET imaging with a fast-scanning confocal microscope revealed that cells
      containing activated caspases showed typical and nontypical apoptotic behavior in
      a region-specific manner during NTC. Inhibiting caspase activation perturbed and
      delayed the smooth progression of cranial NTC, which might increase the risk of
      exencephaly. Our results suggest that caspase-mediated cell removal facilitates
      NTC completion within a limited developmental window.

PMID- 22162137
TI  - A novel PET tracer for the imaging of alphavbeta3 and alphavbeta5 integrins in
      experimental breast cancer bone metastases.
AB  - The aim of this study was the evaluation of (68)Ga-DOTA-E-[c(RGDfK)](2) as a
      novel PET tracer to image alphavbeta3 and alphavbeta5 integrins. For this
      purpose, DOTA-E-[c(RGDfK)](2) was labeled with (68)Ga, which was obtained from a
      (68)Ge/(68)Ga generator, purified by solid-phase extraction and the radiochemical
      purity analyzed by radio-RP-HPLC. (68) Ga-DOTA-E-[c(RGDfK)](2) was obtained
      reproducibly in radiochemical yields of 60 +/- 6% and with an excellent
      radiochemical purity of >99%. In nude rats bearing bone metastases after
      injection of MDA-MB-231 human breast cancer cells, biodistribution studies were
      performed to evaluate the accumulation of the radiotracer in selected organs,
      blood and bone metastases 0.5, 1, 2 and 3 h post injection. A rapid uptake into
      the bone metastases and rapid blood clearance was observed, resulting in tumor
      blood ratios of up to 26.6 (3 h post injection) and tumor-muscle ratios of up to
      7.9 (3 h post injection). A blocking experiment with coinjected
      alphavbeta3/alphavbeta5 antagonist showed the tumor uptake to be receptor
      specific. In an initial in vivo micro PET evaluation of the tracer using the same
      animal model, the bone metastasis was clearly visualized. These results suggest
      that (68)Ga-DOTA-E-[c(RGDfK)](2) is a promising PET tracer suitable for the
      imaging of alphavbeta3 and alphavbeta5 integrins in bone metastases. This novel
      PET tracer should be further evaluated concerning its usefulness for early
      detection of bone metastases and monitoring treatment response of these lesions.

PMID- 22162139
TI  - The monocarboxylate transporter family--role and regulation.
AB  - Monocarboxylate transporter (MCT) isoforms 1-4 catalyze the proton-linked
      transport of monocarboxylates such as L-lactate across the plasma membrane,
      whereas MCT8 and MCT10 are thyroid hormone and aromatic amino acid transporters,
      respectively. The importance of MCTs is becoming increasingly evident as their
      extensive physiological and pathological roles are revealed. MCTs 1-4 play
      essential metabolic roles in most tissues with their distinct properties,
      expression profile, and subcellular localization matching the particular
      metabolic needs of a tissue. Important metabolic roles include energy metabolism
      in the brain, skeletal muscle, heart, tumor cells, and T-lymphocyte activation,
      gluconeogenesis in the liver and kidney, spermatogenesis, bowel metabolism of
      short-chain fatty acids, and drug transport. MCT8 is essential for thyroid
      hormone transport across the blood-brain barrier. Genetic perturbation of MCT
      function may be involved in disease states such as pancreatic beta-cell
      malfunction (inappropriate MCT1 expression), chronic fatigue syndromes
      (impairment of muscle MCT function), and psychomotor retardation (MCT8 mutation).
      MCT expression can be regulated at both the transcriptional and post
      transcriptional levels. Of particular importance is the upregulation of muscle
      MCT1 expression in response to training and MCT4 expression in response to
      hypoxia. The latter is mediated by hypoxia inducible factor 1alpha and often
      observed in tumor cells that rely almost entirely on glycolysis for their energy
      provision. The recent discovery of potent and specific MCT1 inhibitors that
      prevent proliferation of T-lymphocytes confirms that MCTs may be promising
      pharmacological targets including for cancer chemotherapy.

PMID- 22162138
TI  - Factors associated with psychological distress following colposcopy among women
      with low-grade abnormal cervical cytology: a prospective study within the Trial
      Of Management of Borderline and Other Low-grade Abnormal smears (TOMBOLA).
AB  - BACKGROUND: Little is known about psychological after-effects of colposcopy and
      associated investigations and treatment in women with low-grade abnormal cervical
      cytology. We investigated psychological distress following colposcopy and related
      procedures. METHODS: Nine hundred and eighty-nine women aged 20-59 years with
      routine cytology showing low-grade abnormalities were recruited to the Trial of
      Management of Borderline and other Low-grade Abnormal smears and attended
      colposcopy. If the cervical transformation zone (TZ) was colposcopically
      abnormal, women had immediate loop excision or diagnostic punch biopsies, with
      treatment if these showed cervical intraepithelial neoplasia grade 2/3 (CIN2/3).
      Women completed socio-demographic and psychosocial questionnaires at recruitment
      and before colposcopy. Six weeks after their last procedure, women completed the
      Impact of Event Scale (IES). Logistic regression was used to determine factors
      associated with significant psychological distress (IES >= 9). Analyses were
      stratified by colposcopic impression. RESULTS: The response rate was 74%. Six
      weeks after the last procedure, 86 (21%) of 391 women with a normal TZ had
      significant distress compared with 144 (42%) of 337 with an abnormal TZ. In both
      groups, significant distress was associated with anxiety pre-colposcopy and pain
      or discharge afterwards. Additional variables predicting distress in women with a
      normal TZ were worries about having sex and dissatisfaction with support from
      others. In women with an abnormal TZ, additional predictors of distress were
      younger age, CIN2/3, bleeding following colposcopy and worries about having
      cancer. CONCLUSIONS: Substantial proportions of women experience psychological
      distress after colposcopy and related procedures, even when the colposcopy is
      normal. This is an important cost of cervical screening. Interventions to
      alleviate these adverse psychological effects are required.

PMID- 22162142
TI  - The laryngeal saccule: clinical significance.
AB  - The association between the laryngeal saccule and a laryngocele is an important
      clinical relationship. Here, we describe this and other clinical correlations of
      the saccule including infection and carcinoma and suggest that these should be
      discussed in medical gross anatomy courses. We also briefly present some
      descriptive information on the anatomy and function of the saccule in humans and
      other higher primates.

PMID- 22162140
TI  - Effects of disease-modifying antirheumatic drugs on nonvertebral fracture risk in
      rheumatoid arthritis: a population-based cohort study.
AB  - Several prior investigations demonstrate an improvement in bone mineral density
      associated with use of tumor necrosis factor inhibitors (TNFi). We compared the
      risk of osteoporotic fractures among patients with rheumatoid arthritis (RA)
      initiating a disease-modifying antirheumatic drug (DMARD). A population-based
      cohort study was conducted using health care utilization data (1996-2008) from a
      Canadian province and a U.S. commercial insurance plan. Patients with at least
      two RA diagnoses were identified, and follow-up began with the first prescription
      for a DMARD. Drug regimens were categorized into three mutually exclusive
      hierarchical groups: (1) TNFi with or without nonbiologic DMARDs (nbDMARD), (2)
      methotrexate (MTX) without a TNFi, or (3) other nbDMARD without a TNFi or MTX.
      Main outcomes were hospitalizations for fractures of the hip, wrist, humerus, or
      pelvis based on diagnoses and procedure codes. The study cohort consisted of
      16,412 RA patients with 25,988 new treatment episodes: 5856 TNFi, 12,554 MTX, and
      7578 other nbDMARD. The incidence rate per 1000 person-years for osteoporotic
      fracture were 5.11 [95% confidence interval (CI) 3.50-7.45] for TNFi, 5.35 (95%
      CI 4.08-7.02) for MTX, and 6.38 (95% CI 3.78-10.77) for other nbDMARD. After
      multivariable adjustment for osteoporosis and fracture-related risk factors, the
      risk of nonvertebral osteoporotic fracture was not different in either TNFi
      [hazard ratio (HR) 1.07, 95% CI 0.57-1.98] or MTX (HR 1.18, 95% CI 0.60-2.34)
      compared with nbDMARD. Among subjects diagnosed with RA, the adjusted risk of
      nonvertebral fracture was similar across persons starting a TNFi, MTX, or other
      nbDMARD.

PMID- 22162141
TI  - StarClose vascular closure system (VCS) is safe and effective in patients who
      ambulate early following successful femoral artery access closure--results from
      the RISE clinical trial.
AB  - OBJECTIVE: The RISE study was a prospective, multicenter, single-arm study
      evaluating the safety and efficacy of the StarClose Vascular Closure System (VCS)
      in the femoral artery in subjects who were ambulated early following percutaneous
      diagnostic coronary or peripheral catheterization procedures. BACKGROUND:
      Previous studies have demonstrated that several vascular closure devices are able
      to safely decrease the amount of bedrest needed following angiography. To date,
      no device has been shown to be safe for immediate ambulation. METHODS: Between
      April 2006 and November 2006, 315 patients undergoing a catheterization via the
      femoral artery were enrolled (intent-to-treat population, ITT). Of these, 171
      subjects were not excluded by angiographic or clinical criteria and had a
      StarClose device placed to attain hemostasis. If hemostasis was immediately
      achieved, patients were ambulated within 20 min for 20 feet without assistance
      (per-protocol population, PP). Patients were followed for 30 days after the index
      procedure. The primary endpoint of the study was time to ambulation (TTA).
      RESULTS: Immediate hemostasis was achieved in 156 patients (91.2%). The mean TTA
      in the PP was 8.29 min, median 5.92. There were no deaths or major vascular
      complications, and the rate of minor vascular complications was 1.9% (3/156).
      CONCLUSION: The StarClose VCS device is both safe and effective allowing
      immediate ambulation of patients who have undergone catheterization via the
      femoral artery.

PMID- 22162143
TI  - Tumor histology during induction therapy in patients with high-risk
      neuroblastoma.
AB  - BACKGROUND: In high-risk neuroblastoma patients, response to induction
      chemotherapy is emerging as an important determinant of overall survival. We
      sought to determine whether histological changes in the primary tumor following
      induction therapy could be used as a marker of response. PROCEDURE: Second-look
      primary tumor specimens from 43 patients were reviewed according to specific
      morphological features. RESULTS: In the majority, induction therapy resulted in a
      shift from an intermediate/high to low mitosis-karyorrhexis index (MKI) (P =
      0.0009) and from undifferentiated/poorly differentiated to differentiating tumors
      (P < 0.0001). Following induction therapy, persistence of intermediate/high tumor
      MKI and >=90% persistent neuroblastic cells were predictive of a poor outcome (P
      = 0.001 and 0.03, respectively). Less than 10% tumor necrosis was associated with
      a trend towards lower survival. CONCLUSIONS: High proliferative activity in the
      primary tumor following induction therapy portends a poor outcome in patients
      with high-risk neuroblastoma. If confirmed in a larger cohort, tumor histology at
      second-look surgery could be used to define a subset of very high risk patients
      who would benefit from alternative therapies prior to myeloablative dose
      intensive transplant.

PMID- 22162144
TI  - Clinical validation of Movement Disorder Society-recommended diagnostic criteria
      for Parkinson's disease with dementia.
AB  - The objective of this work was to evaluate the Movement Disorders Society (MDS)
      Task Force-proposed screening checklist for detecting Parkinson's disease
      dementia (PD-D) in relation to full neuropsychological testing. An MDS Task Force
      has proposed diagnostic procedures for PD-D, which have not been fully validated
      against more extensive neuropsychological testing. PD subjects were recruited
      from 2 specialty centers. A neuropsychologist evaluated them for dementia as part
      of routine clinical care. Independent clinical neurologists administered the MDS
      PD-D screening checklist. Diagnosis of PD-D by the 2 methods was compared. Ninety
      one PD subjects had a mean age of 66.3 (SD = 9.7) years and a mean PD duration of
      8.8 (SD = 6.1) years. Seven subjects (7.7%) met all 8 screening checklist
      criteria from the MDS PD-D screening tool and were classified as probable PD-D.
      Fifteen (16.5%) subjects were classified as PD-D by full neuropsychological
      assessment. The screening checklist showed 100% specificity, but only 46.7%
      sensitivity, for diagnosing PD-D compared to the full neuropsychological
      assessment. PD-D cases missed by the PD-D screening tool were largely due to 2
      checklist items that were not endorsed (absence of depression and Mini-Mental
      State Examination [MMSE] scores <26). There was moderate agreement between these
      2 methods for determination of PD-D (kappa = 0.59, P < .001). The MDS-PD-D
      screening checklist is highly accurate for detecting PD-D if all items are
      endorsed. However, for cases that do not meet these criteria, full
      neuropsychological testing is needed to differentiate PD-D from milder cognitive
      impairment. Revision of the checklist by altering or eliminating the 2
      problematic checklist items may improve sensitivity.

PMID- 22162145
TI  - Neural correlates of creative writing: an fMRI study.
AB  - Cerebral activations involved in actual writing of a new story and the associated
      correlates with creative performance are still unexplored. To investigate the
      different aspects of the creative writing process, we used functional magnetic
      resonance imaging while 28 healthy participants performed a new paradigm related
      to creative writing: "brainstorming" (planning a story) and "creative writing"
      (writing a new and creative continuation of a given literary text), as well as an
      additional control paradigm of "reading" and "copying." Individual verbal
      creativity was assessed with a verbal creativity test and creative performance
      with a qualitative rating of the creative products. "brainstorming" engaged
      cognitive, linguistic, and creative brain functions mainly represented in a
      parieto-frontal-temporal network, as well as writing preparation, and visual and
      imaginative processing. "creative writing" activated motor and visual brain areas
      for handwriting and additionally, cognitive and linguistic areas. Episodic memory
      retrieval, free-associative and spontaneous cognition, and semantic integration
      were observed in a right lateralized activation pattern in bilateral hippocampi,
      bilateral temporal poles (BA 38), and bilateral posterior cingulate cortex in a
      "creative writing" minus "copying" comparison. A correlation analysis of
      "creative writing" minus "copying" with the creativity index revealed activation
      in the left inferior frontal gyrus (BA 45) and the left temporal pole (BA 38).
      Thus, verbal creativity during "creative writing" is associated with verbal and
      semantic memory as well as semantic integration.

PMID- 22162146
TI  - Three-component [2+2+2] cycloaddition of carboryne, unactivated alkene, and
      alkyne via zirconacyclopentane mediated by nickel: one-pot synthesis of
      dihydrobenzocarboranes.

PMID- 22162148
TI  - Reactivity and mechanistic insight into visible-light-induced aerobic cross
      dehydrogenative coupling reaction by organophotocatalysts.
AB  - With visible-light irradiation, a mild, simple, and efficient metal-free
      photocatalytic system for the facile construction of sp(3)-sp(3) C-C bonds
      between tertiary amines and activated C-H bonds has been achieved. Spectroscopic
      study and product analysis demonstrate for the first time that photoinduced
      electron transfer from N-aryl tetrahydroisoquinolines to eosin Y
      bis(tetrabutylammonium salt) (TBA-eosin Y) takes place to generate TBA-eosin Y
      radical anion, which can subsequently react with nucleophiles and molecular
      oxygen. More strikingly, electron spin resonance (ESR) measurements provide
      direct evidence for the formation of superoxide radical anions (O(2)(-.)) rather
      than singlet oxygen ((1)O(2)) during visible-light irradiation. This active
      species is therefore believed to be responsible for the large rate of
      acceleration of the aerobic photocatalytic reactions.

PMID- 22162147
TI  - An activity-based imaging probe for the integral membrane hydrolase KIAA1363.

PMID- 22162149
TI  - Baculovirus-mediated vascular endothelial growth factor-D(DeltaNDeltaC)  gene
      transfer induces angiogenesis in rabbit skeletal muscle.
AB  - BACKGROUND: Occluded arteries and ischemic tissues cannot always be treated by
      angioplasty, stenting or by-pass-surgery. Under such circumstances, viral gene
      therapy may be useful in inducing increased blood supply to ischemic area. There
      is evidence of improved blood flow in ischemic skeletal muscle and myocardium in
      both animal and human studies using adenoviral vascular endothelial growth factor
      (VEGF) gene therapy. However, the expression is transient and repeated gene
      transfers with the same vector are inefficient due to immune responses. METHODS:
      Different baculoviral vectors pseudotyped with or without vesicular stomatitis
      virus glycoprotein (VSV-G) and/or carrying woodchuck hepatitis virus post
      transcriptional regulatory element (Wpre) were tested both in vitro and in vivo.
      VEGF-D(DeltaNDeltaC) was used as therapeutic transgene and lacZ as a control. In
      vivo efficacy was evaluated as capillary enlargement and transgene expression in
      New Zealand White (NZW) rabbit skeletal muscle. RESULTS: A statistically
      significant capillary enlargement was detected 6 days after gene transfer in
      transduced areas compared to the control gene transfers with baculovirus and
      adenovirus encoding beta-galactosidase (lacZ). Substantially improved gene
      transfer efficiency was achieved with a modified baculovirus pseudotyped with VSV
      G and carrying Wpre. Dose escalation experiments revealed that either too large
      volume or too many virus particles caused inflammation and necrosis in the target
      tissue, whereas 10(9) plaque forming units injected in multiple aliquots resulted
      in transgene expression with only mild immune reactions. CONCLUSIONS: We show the
      first evidence of biologically significant baculoviral gene transfer in skeletal
      muscle of NZW rabbits using VEGF-D(DeltaNDeltaC) as a therapeutic transgene.

PMID- 22162151
TI  - Sample size calculations with multiplicity adjustment for longitudinal clinical
      trials with missing data.
AB  - Missing data are ubiquitous in longitudinal clinical trials, and the impact on
      power has been extensively assessed in the literature. Multiple doses of the
      investigational product and multiple efficacy endpoints are often studied in
      randomized clinical trials and multiplicity adjustment needs to be considered in
      the sample size calculations. In this paper, I show how to perform sample size
      calculations with multiplicity adjustment for longitudinal clinical trials with
      missing data by converting longitudinal data with missing data to cross-sectional
      data without missing data. The proposed approach can drastically simplify the
      simulation work and facilitate the evaluation of power for various scenarios.

PMID- 22162152
TI  - Morphological defects in a novel Rdh10 mutant that has reduced retinoic acid
      biosynthesis and signaling.
AB  - Retinoic acid (RA) signaling is necessary for proper patterning and morphogenesis
      during embryonic development. Tissue-specific RA signaling requires precise
      spatial and temporal synthesis of RA from retinal by retinaldehyde dehydrogenases
      (Raldh) and the conversion of retinol to retinal by retinol dehydrogenases (Rdh)
      of the short-chain dehydrogenase/reducatase gene family (SDR). The SDR, retinol
      dehydrogenase 10 (RDH10), is a major contributor to retinal biosynthesis during
      mid-gestation. We have identified a missense mutation in the Rdh10 gene
      (Rdh10(m366Asp) ) using an N-ethyl-N-nitrosourea-induced forward genetic screen
      that result in reduced RA levels and signaling during embryonic development.
      Rdh10(m366Asp) mutant embryos have unique phenotypes, such as edema, a massive
      midline facial cleft, and neurogenesis defects in the forebrain, that will allow
      the identification of novel RA functions.

PMID- 22162153
TI  - Photodegradable polymers for biotechnological applications.
AB  - Photodegradable polymers constitute an emerging class of materials that finds
      numerous applications in biotechnology, biomedicine, and nanoscience. This
      article highlights some of the emerging applications of photodegradable polymers
      in the form of homopolymers, particles and self-assembled constructs in solution,
      hydrogels for tissue engineering, and photolabile polymers for biopatterning
      applications. Novel photochemistries have been combined with controlled
      polymerization methods, which result in well-defined photodegradable materials
      that exhibit light mediated and often controlled fragmentation processes.

PMID- 22162154
TI  - Somatotopic arrangement of thermal sensory regions in the healthy human spinal
      cord determined by means of spinal cord functional MRI.
AB  - Previous functional MRI studies of normal sensory function in the human spinal
      cord, including right-to-left symmetry of activity, have been influenced by order
      effects between repeated studies. In this study, we apply thermal sensory
      stimulation to four dermatomes within each functional MRI time-series
      acquisition. Each of the four dermatomes receives a unique stimulation paradigm,
      such that the four paradigms form a linearly independent set, enabling detection
      of each individual stimulus response. Functional MRI data are shown spanning the
      cervical spinal cord and brainstem in 10 healthy volunteers. Results of general
      linear model analysis demonstrate consistent patterns of activity within the
      spinal cord segments corresponding to each dermatome, and a high degree of
      symmetry between right-side and left-side stimulation. Connectivity analyses also
      demonstrate consistent areas of activity and connectivity between spinal cord and
      brainstem regions corresponding to known anatomy. However, right-side and left
      side responses are not at precisely the same rostral-caudal positions, but are
      offset by several millimeters, with left-side responses consistently more caudal
      than right-side responses. The results confirm that distinct responses to
      multiple interleaved sensory stimuli can be distinguished, enabling studies of
      sensory responses within the spinal cord without the confounding effects of
      comparing sequential studies.

PMID- 22162155
TI  - Helical content of a beta(3)-octapeptide in methanol: molecular dynamics
      simulations explain a seeming discrepancy between conclusions derived from CD and
      NMR data.
AB  - Connecting experimental observables with the underlying conformational ensemble
      is a long-standing problem in the structure determination of biomolecules. The
      simulations described in this article attempt to resolve a seeming discrepancy
      between the conformational features derived from measured NOE intensities, (3)J
      coupling constants, and circular dichroism (CD) spectra for two beta-peptides
      differing in a linker between two side-chains. Although both peptides are very
      similar in terms of the r(-6) averaged distances between atom pairs involved in
      the observed NOEs, the molecular dynamics trajectories suggest why the CD spectra
      show a greater 3(14)-helical propensity for the linked, cyclic peptide than for
      the linear one, whereas slightly more NMR NOE peaks are observed and assigned for
      the latter. The nine 100 ns unrestrained simulations show better agreement with
      the observed experimental data than the single conformations derived from the
      published NMR structures by additional energy minimization with the GROMOS force
      field. They show why the seemingly contradictory quantities obtained by NMR and
      CD spectroscopy can arise from a single conformational ensemble.

PMID- 22162156
TI  - Chemical constituents of plants from the genus Simaba (Simaroubaceae).

PMID- 22162157
TI  - Glandular trichomes and essential oil composition of endemic Sideritis italica
      (Mill.) Greuter et Burdet from central Italy.
AB  - Sideritis italica (Mill.) Greuter et Burdet belongs to the Lamiaceae family and
      is endemic to Italy. The glandular trichomes (morphology, distribution,
      histochemistry, and ultrastructure) of the plant were studied for the first time,
      along with the chemical composition of the essential oils. Abundant non-glandular
      hairs and peltate (type A) and capitate (types B, C(1), and C(x)) glandular
      trichomes were observed both on the vegetative and reproductive organs. The
      histochemical procedures and the ultrastructural investigation enabled specific
      location of the main site of essential oil production mainly in type-A peltate
      hairs. Particular emphasis is given to the release mechanism of the secreted
      material in all of the types of glands, and the potential taxonomic value of the
      indumentum in the Lamiaceae family is briefly discussed. Essential oils were
      hydrodistilled from flowering aerial parts of S. italica, and 136 compounds (112
      in flowerheads, 79 in vegetative parts) were identified. The quantitative
      prevalence of diterpenoids (43.4% in flowerheads and 22.3% in vegetative parts)
      was the most significant characteristic of the essential oil of S. italica that
      could be classified as a diterpene-rich essential oil according to the
      classification of Kirimer.

PMID- 22162158
TI  - Gel formulation containing mixed surfactant and lipids associating with
      carboplatin.
AB  - The interaction of amphiphilic molecules such as lipids and surfactants with the
      hydrophilic drug carboplatin was investigated to identify suitable self
      assembling components for a potential gel-based delivery formulation. (1) H-NMR
      Studies in sodium bis(2-ethylhexyl) sulfosuccinate (aerosol-OT, AOT)-based
      reverse micelles show that carboplatin associates and at least partially
      penetrates the surfactant interface. Langmuir monolayers formed by
      dipalmitoyl(phosphatidyl)choline are penetrated by carboplatin. Carboplatin was
      found to also penetrate the more rigid monolayers containing cholesterol. A
      combined mixed surfactant gel formulation containing carboplatin and cholesterol
      for lymphatic tissue targeting was investigated for the intracavitary treatment
      of cancer. This formulation consists of a blend of the surfactants lecithin and
      AOT (1 : 3 ratio), an oil phase of isopropyl myristate, and an aqueous component.
      The phases of the system were defined within a pseudo-ternary phase diagram. At
      low oil content, this formulation produces a gel-like system over a wide range of
      H(2) O content. The carboplatin release from the formulation displays a prolonged
      discharge with a rate three to five times slower than that of the control.
      Rheological properties of the formulation exhibit pseudoplastic behavior.
      Microemulsion and Langmuir monolayer studies support the interactions between
      carboplatin and amphiphilic components used in this formulation. To target
      delivery of carboplatin, two formulations containing cholesterol were
      characterized. These two formulations with cholesterol showed that, although
      cholesterol does little to alter the phases in the pseudo-ternary system or to
      increase the initial release of the drug, it contributes significantly to the
      structure of the formulation under physiological temperature, as well as
      increases the rate of steady-state discharge of carboplatin.

PMID- 22162159
TI  - Variation in physical and chemical characteristics of common bean (Phaseolus
      vulgaris L.) grain along a domestication gradient.
AB  - The objective of this study was to compare six samples of Mexican wild common
      bean (Phaseolus vulgaris L.) against three landraces and three improved cultivars
      with respect to physical and chemical attributes, and the culinary quality
      potential of their grain. A completely randomized experimental design was used to
      characterize the twelve genotypes. Data were analyzed by analysis of variance and
      pair-wise comparison of the treatment means by the Tukey test. In addition,
      correlation and principal-component analysis (PCA) were carried out using twelve
      characteristics of raw and four of cooked wild and domesticated grains. The
      results show a larger variability of the physical and chemical characteristics in
      wild than in domesticated beans. The PCA confirmed that grain gigantism was the
      main physical characteristic resulting of domestication, whereas the protein and
      tryptophan contents tended to be higher in wild than domesticated genotypes. Some
      wild samples from Chihuahua and Durango, Mexico, showed to be a genetic resource
      to improve food quality, because of their richness in minerals, protein, lysine,
      tryptophan, and dietary fibers.

PMID- 22162160
TI  - Secondary metabolite profile in induced tetraploids of wild Solanum commersonii
      Dun.
AB  - The main aim of this work was to study the leaf secondary metabolite profiles of
      artificially induced tetraploids (2n=4x=48) of Solanum commersonii, a diploid
      (2n=2x=24) wild potato species. The tetraploid genotypes of S. commersonii were
      produced by oryzalin treatment. Both HPLC-UV and LC/MS analyses revealed that
      there were no qualitative differences in the metabolite profiles between the
      diploid S. commersonii and its tetraploids. By contrast, the results showed that
      the phenylpropanoid content was generally significantly higher in the tetraploids
      than in the diploid S. commersonii. Concerning the glycoalkaloids (GAs), the
      results provided evidence that the content of minor GAs (solanidenediol triose,
      solanidadienol lycotetraose, and solanidenol lycotetraose) was higher in
      tetraploids than in the diploid progenitor, while the content of major GAs
      (dehydrodemissine and dehydrocommersonine) was significantly higher in diploid S.
      commersonii than in its tetraploid genotypes. The results are discussed from the
      practical perspective of potato biodiversity enhancement.

PMID- 22162161
TI  - Intracolonial allocation of trisoxazole macrolides in the sponge Pachastrissa
      nux.
AB  - Pachastrissa nux has two distinctive growth forms in one colony, i.e., the
      protruding gorgonian-shaped capitum and the substratum-attached irregular-shaped
      base. The sponge has the ability to allocate specifically its major secondary
      metabolites to the two parts in different levels. Using two cytotoxic trisoxazole
      macrolides, kabiramides C (2) and G (3), as chemical markers, it was found that
      the capitum accumulated higher contents of either or both compounds than did the
      base. However, there were neither inductive nor suppressive correlations among
      the allocation profiles of either compound in either part of the sponge. The
      allocation of kabiramides was a trade-off with the structural materials involved
      in reinforcing the strength of the sponge. To date, this is the second report
      that provides evidence of the specific allocation of bioactive metabolites in two
      distinctively different organ-like structures in a single sponge colony.

PMID- 22162162
TI  - Terpene chemodiversity of relict conifers Picea omorika, Pinus heldreichii, and
      Pinus peuce, endemic to Balkan.
AB  - Terpenes are often used as ecological and chemotaxonomic markers of plant
      species, as well as for estimation of geographic variability. Essential oils of
      relic and Balkan endemic/subendemic conifers, Picea omorika, Pinus heldreichii,
      and P. peuce, in central part of Balkan Peninsula (Serbia and Montenegro), on the
      level of terpene classes and common terpene compounds were investigated. In
      finding terpene combinations, which could show the best diversity between species
      and their natural populations, several statistical methods were applied. Apart
      from the content of different terpene classes (P. omorika has the most abundant O
      containing monoterpenes and sesquiterpenes; P. heldreichii and P. peuce have the
      largest abundance of sesquiterpene and monoterpene hydrocarbons, resp.), the
      species are clearly separated according to terpene profile with 22 common
      compounds. But, divergences in their populations were established only in
      combination of several compounds (specific for each species), and they were found
      to be the results of geomorphologic, climatic, and genetic factors. We found
      similarities between investigated species and some taxa from literature with
      respect to terpene composition, possibly due to hybridization and phylogenetic
      relations. Obtained results are also important regarding to chemotaxonomy,
      biogeography, phylogeny, and evolution of these taxa.

PMID- 22162163
TI  - D-ring-opened phragmalin-type limonoids from Chukrasia tabularis var. velutina.
AB  - Five new D-ring-opened phragmalin-type limonoids, tabulalins A-E (1-5, resp.),
      were isolated from the stem bark of Chukrasia tabularis var. velutina. In the
      structures of these new isolates, the D-ring (C(16)/C(17) delta-lactone ring) of
      phragmalins was cleaved, and rare C(16)/C(30) delta-lactone ring in 1-3 or
      C(16)/C(8) gamma-lactone ring in 4 and 5 were formed. The structures of these new
      compounds were elucidated based on extensive 1D- and 2D-spectroscopic analyses
      (HSQC, HMBC, and ROESY) and HR-ESI-MS. The major compounds, 2, 3, and 5, were
      evaluated for their inhibitory activities against lipopolysaccharide (LPS)
      induced nitric oxide (NO) production in a macrophage (RAW264.7) cell line with
      IC(50) values of 15.3+/-0.6, 13.0+/-0.5, and 17.1+/-0.7 MUM, respectively.

PMID- 22162164
TI  - Sesquiterpenoids and diarylheptanoids from Nidus vespae and their inhibitory
      effects on nitric oxide production.
AB  - Two coriamyrtin-type sesquiterpenes, fengfangin A (1) and tutin (2), and six
      diarylheptanoids, namely alnusone (3), centrolobol (4), muricarpone B (5), 1-(3,4
      dihydroxyphenyl)-7-(4-hydroxyphenyl)heptan-3-one (6), (3S)-1-(3,4
      dihydroxyphenyl)-7-(4-hydroxyphenyl)heptan-3-ol (7), and (3S)-1-(4-hydroxyphenyl)
      7-(3,4-dihydroxyphenyl)heptan-3-ol (8), were isolated from the 95% EtOH extract
      of nidus vespae, the nest of Polistes species. Their structures were identified
      by spectroscopic methods. Compounds 1 and 8 are new products. The absolute
      configuration of 1 was determined by single-crystal X-ray diffraction analysis
      using Flack parameter. The biological tests showed that compounds 5, 6, and 8
      could inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated
      RAW 264.7 cells with IC(50) values in the range of 13-17 MUM, whereas the
      sesquiterpenes were inactive in this assay (>25 MUM). In addition, the ecological
      significance of the presence of neurotoxic sesquiterpene lactones in nidus vespae
      is briefly discussed.

PMID- 22162165
TI  - Two novel steroidal alkaloid glycosides from the seeds of Lycium barbarum.
AB  - Two novel steroidal alkaloid glycosides, lycioside A (1) and lycioside B (2) were
      isolated from the seeds of Lycium barbarum. Their structures were determined by
      various spectroscopic analyses. Compounds 1 and 2 showed inhibitory activities
      with the IC(50) values of 75.3 and 72.8 MUM against rat intestinal sucrase, and
      63.4 and 59.1 MUM against rat intestinal maltase.

PMID- 22162166
TI  - Chemical constituents of the fermented broth of the ascomycete Theissenia cinerea
      89091602.
AB  - One new betaenone, theissenoic acid (1), together with three new acetogenins,
      theissenolactones A-C (2-4, resp.), were isolated from the fermented broth of
      Theissenia cinerea 89091602 isolated in Taiwan. The structures of 1-4 were
      elucidated by spectroscopic methods. Biological tests revealed that 3 and 4
      exhibited moderate growth-inhibitory activities against A549 lung cancer cell
      line with GI(50) values of 14.9 and 47.9 MUM, respectively.

PMID- 22162167
TI  - Terpenoids from Maytenus species and assessment of their reversal activity
      against a multidrug-resistant Leishmania tropica line.
AB  - The phytochemical analysis of the root bark extracts of the Chilean Maytenus, M.
      chubutensis, and M. magellanica (Celastraceae), led to the isolation of one
      phenolic nortriterpene, 1, and one diterpene with a nor-ent-kaurene skeleton, 2.
      In addition, four known compounds were isolated, among which compound 3 has been
      isolated for the first time from a natural source. Their structures were
      elucidated by spectroscopic methods, including 1D- and 2D-NMR (COSY, ROESY, HSQC,
      and HMBC) experiments, comparison with data reported in the literature, and
      chemical correlations. The isolated compounds were assayed for their reversal
      activity against a multidrug-resistant Leishmania tropica line, overexpressing a
      P-glycoprotein related transporter. Compound 1 showed moderate multidrug
      resistance reversal activity.

PMID- 22162168
TI  - Phenolic compounds of Abies nephrolepis and their NO production inhibitory
      activities.
AB  - Two new, i.e., 1 and 2, and 69 known phenolics were isolated from the aerial
      parts of Abies nephrolepis. These chemical constituents included 22 lignans, 30
      flavonoids, and 19 other phenols. Their structures were determined mainly by
      analysis of the 1D- and 2D-NMR spectroscopic data. All the 71 isolates were
      evaluated for their inhibitory activities against lipopolysaccharide (LPS)
      induced NO production in RAW 264.7 macrophages. Compound 1 exhibited a potent
      effect with an IC(50) value of 13.7 MUg/ml.

PMID- 22162169
TI  - Glucosinolate profiling and antimicrobial screening of Aurinia leucadea
      (Brassicaceae).
AB  - Glucosinolates (GLs) were characterized in various aerial parts (stems, leaves,
      and flowers) of Aurinia leucadea (Guss.) C. Koch and quantified according to the
      ISO 9167-1 official method based on the HPLC analysis of desulfoglucosinolates.
      Eight GLs, i.e., glucoraphanin (GRA), glucoalyssin (GAL; 1), gluconapin (GNA; 2),
      glucocochlearin (GCC), glucobrassicanapin (GBN; 3), glucotropaeolin (GTL),
      glucoerucin (GER), and glucoberteroin (GBE) were identified. The total GL
      contents were 57.1, 37.8, and 81.3 MUmol/g dry weight in the stems, leaves, and
      flowers, respectively. The major GL detected in all parts of the plant was 2,
      followed by 1 and 3. GC/MS Analysis of the volatile fractions extracted from the
      aerial parts of fresh plant material either by hydrodistillation or CH(2) Cl(2)
      extraction showed that these fractions mostly contained isothiocyanates (ITCs).
      The main ITCs were but-3-enyl- (55.6-71.8%), pent-4-enyl- (7.6-15.3%), and 5
      (methylsulfinyl)pentyl ITC (0-9.5%), originating from the corresponding GLs 2, 3,
      and 1, respectively. The antimicrobial activity of the volatile samples was
      investigated by determining inhibition zones with the disk-diffusion method and
      minimal inhibitory concentrations (MIC) with the microdilution method. They were
      found to inhibit a wide range of bacteria and fungi, with MIC values of 2.0-32.0
      MUg/ml, indicating their promising antimicrobial potential, especially against
      the fungi Candida albicans and Rhizopus stolonifer as well as against the
      clinically important pathogen Pseudomonas aeruginosa.

PMID- 22162170
TI  - 'Tocol-omic' diversity in wild barley, short communication.
AB  - Hordeum spontaneum, wild barley, is the direct progenitor of domestic barley,
      Hordeum vulgare, an economically important ingredient of animal feed, beer, soy
      sauce, and more recently, of nutraceuticals. Domestic barley has also been used
      in the past as a medicine. Barley is a rich source of tocotrienols, with alpha
      tocotrienol being the most prevalent. Wild barley seeds were harvested from
      ecogeographically diverse areas across the Fertile Crescent, and the tocopherol
      (alpha-delta) and tocotrienol (alpha-delta) contents were determined. Diversity
      differences in individual and total 'tocol' values were significant between and
      within specific countries, and were significantly correlated with temperature.
      Wild barley may be used in the future to improve functional qualities of domestic
      barley. 'Tocolome' and 'tocolomics' are proposed to encompass all tocols and
      potentially synergy-enhancing 'entourage' compounds that may occur in tocols'
      'metabolomic neighborhoods', aiding the standardized manufacture of complex
      barley derivatives for nutraceutical and pharmaceutical functions.

PMID- 22162171
TI  - Antifungal metabolites from the roots of Diospyros virginiana by overpressure
      layer chromatography.
AB  - A preparative overpressure layer chromatography (OPLC) method was successfully
      used for the separation of two new natural compounds, 4-hydroxy-5,6
      dimethoxynaphthalene-2-carbaldehyde (1) and 12,13-didehydro-20,29-dihydrobetulin
      (2) together with nine known compounds, including 7-methyljuglone (3), diospyrin
      (4), isodiospyrin (5), shinanolone (6), lupeol (7), betulin (8), betulinic acid
      (9), betulinaldehyde (10), and ursolic acid (11) from the acetone extract of the
      roots of Diospyros virginiana. Their identification was accomplished by 1D- and
      2D-NMR spectroscopy and HR-ESI-MS methods. All the isolated compounds were
      evaluated for their antifungal activities against Colletotrichum fragariae, C.
      gloeosporioides, C. acutatum, Botrytis cinerea, Fusarium oxysporum, Phomopsis
      obscurans, and P. viticola using in vitro micro-dilution broth assay. The results
      indicated that compounds 3 and 5 showed high antifungal activity against P.
      obscurans at 30 MUM with 97.0 and 81.4% growth inhibition, and moderate activity
      against P. viticola (54.3 and 36.6%). It appears that an optimized OPLC system
      offers a rapid and efficient method of exploiting bioactive natural products.

PMID- 22162173
TI  - Selective separation of magnolol using molecularly imprinted membranes.
AB  - Molecularly imprinted membranes (MIMs) for selective separation of magnolol were
      prepared by thermal polymerization using magnolol as the template, ethylene
      glycol dimethacrylate (EGDMA) as the cross-linker, 2,2-azobisisobutyronitrile
      (AIBN) as the initiator, organic solvent as the porogen, methacrylamide (MAM) and
      acrylic acid (AA) as the functional monomers and cellulose acetate as the
      agglutinant. Commercial filter paper was used as the supporting material. The
      effects of different porogens and the ratio of functional monomers on the binding
      and recognition capacity of MIMs were investigated, and the morphology of the
      membranes was examined by scanning electron microscopy (SEM). The results showed
      that the MIMs have the highest selectivity to magnolol when the ratio of MAM/AA
      was 1:4 and tetrahydrofuran (THF) with dimethyl sulfoxide (DMSO) was used as the
      porogen. The morphology of the imprinted membranes after template extracting is
      much rougher with big cavities than that of the non-imprinted membranes (NIMs)
      and the imprinted membranes before template extracting. The MIMs can selectively
      separate the magnolol. 

PMID- 22162174
TI  - Hydration and nutrition at the end of life: a systematic review of emotional
      impact, perceptions, and decision-making among patients, family, and health care
      staff.
AB  - BACKGROUND: Decrease in oral intake, weight loss, and muscular weakness in the
      last phases of a terminal illness, particularly in the context of the cachexia
      anorexia syndrome, can be an important source of anxiety for the triad of
      patient, family, and health staff. METHODS: The present literature review
      examines the emotional impact of reduced oral intake as well as perceptions and
      attitudes toward assisted nutrition and hydration for terminally ill patients(1) 
      at the end of life, among patients, family, and health care staff. We have
      identified the ways in which emotional and cultural factors influence decision
      making about assisted nutrition and hydration. RESULTS: Lack of information and
      misperceptions of medically assisted nutrition and hydration can play a
      predominant role in the decision to begin or suspend nutritional or hydration
      support. CONCLUSIONS: Our literature review reveals that these social, emotional,
      and clinical misperception elements should be considered in the decision-making
      processes to help the triad develop functional forms of care at this final stage
      of life. Copyright (c) 2011 John Wiley & Sons, Ltd.

PMID- 22162175
TI  - Effect of bivalirudin compared with unfractionated heparin plus abciximab on
      infarct size and myocardial recovery after primary percutaneous coronary
      intervention: the horizons-AMI CMRI substudy.
AB  - BACKGROUND: Myocardial infarct size is a strong independent predictor of
      mortality in patients with ST-elevation myocardial infarction (STEMI). In the
      Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial
      Infarction (HORIZONS-AMI) trial, bivalirudin compared with unfractionated heparin
      plus a glycoprotein IIb/IIIa inhibitor reduced cardiac mortality in STEMI
      patients, which was attributed to reduced major bleeding. Whether a possible
      reduction in infarct size with bivalirudin may have contributed to the enhanced
      survival with this agent is unknown. METHODS: Cardiac magnetic resonance imaging
      was performed within 7 days and after 6 months in 51 randomized patients from a
      single center in HORIZONS-AMI trial (N = 28 bivalirudin, N = 23 heparin plus
      abciximab). Infarct size, microvascular obstruction (MVO), left ventricular
      ejection fraction (LVEF), and LV end-diastolic and end-systolic volume indices
      were evaluated. RESULTS: Infarct size was not significantly different after
      treatment with bivalirudin compared with heparin plus abciximab either within 7
      days (median 9.3% [interquartile range 4.9%, 26.6%] vs. 20.0% [5.9%, 28.2%], P =
      0.28) or at 6 months 6.7% [3.8%, 20.0%] vs. 8.2% [1.8%, 16.5%], P = 0.73). MVO
      was present in 28.6% versus 34.8% of patients respectively (P = 0.63). LVEF and
      LV volume indices also did not significantly differ between the two groups at
      either time period, nor were differences in myocardial recovery evident.
      CONCLUSIONS: In conclusion, in the HORIZONS-AMI Cardiac magnetic resonance
      imaging (CMRI) substudy, cardiac magnetic resonance imaging within 7 days and at
      6 months after primary percutaneous coronary intervention (PCI) did not
      demonstrate significant differences in infarct size, MVO, LVEF, or LV volume
      indices in patients treated with bivalirudin compared with unfractionated heparin
      plus abciximab.

PMID- 22162176
TI  - The limited screening value of insulin-like growth factor-I as a marker for
      alterations in body composition in very long-term adult survivors of childhood
      cancer.
AB  - BACKGROUND: The clinical relevance of low IGF-I levels, caused by cranial
      radiotherapy, in adult childhood cancer survivors has not been studied
      extensively. We evaluated whether IGF-I is a useful marker for altered body
      composition and growth hormone deficiency (GHD) in this group. PROCEDURE: We
      analyzed retrospective data from 610 adult childhood cancer survivors, retrieved
      from the late effects clinic. Median age at diagnosis was 6 years (interquartile
      range 3-11) and follow-up time was 18 years (13-24). We assessed IGF-I standard
      deviation scores (SDS), anthropometrical measures, growth hormone stimulation
      tests in patients with clinical signs of GHD, and measures of body composition
      (assessed by dual X-ray absorptiometry, Lunar Prodigy). RESULTS: In 58 cranially
      irradiated acute leukemia survivors (25 Gy (24-25)) and 56 locally irradiated
      brain tumor survivors (42 Gy (35-54)) we found significantly lower IGF-I SDS (P <
      0.001), lower height SDS (P < 0.001), higher body mass index (P = 0.01), higher
      waist-hip ratio (WHR; P = 0.001), higher total fat percentage SDS (P < 0.001),
      and lower lean body mass SDS (P < 0.001), as compared to 452 not cranially
      irradiated survivors. IGF-I showed a weak inverse correlation with BMI (r = 
      0.12, P = 0.04), WHR (r = -0.15, P = 0.01), total fat percentage (r = - 0.14, P =
      0.02), and a positive correlation with lean body mass (r = 0.15, P = 0.01). In
      patients with low IGF-I levels, IGF-I did not significantly differ between
      subjects with and without GHD as determined by GH-stimulation testing (P = 0.39).
      CONCLUSION: This study shows that IGF-I has limited value as a marker for
      alterations in body composition in adult childhood cancer survivors.

PMID- 22162177
TI  - Menstrual cycle-related changes in amygdala morphology are associated with
      changes in stress sensitivity.
AB  - Premenstrual increases in negative mood are thought to arise from changes in
      gonadal hormone levels, presumably by influencing mood regulation and stress
      sensitivity. The amygdala plays a major role in this context, and animal studies
      suggest that gonadal hormones influence its morphology. Here, we investigated
      whether amygdala morphology changes over the menstrual cycle and whether this
      change explains differences in stress sensitivity. Twenty-eight young healthy
      women were investigated once during the premenstrual phase and once during the
      late follicular phase. T1-weighted anatomical images of the brain were acquired
      using magnetic resonance imaging and analyzed with optimized voxel-based
      morphometry. To measure mood regulation and stress sensitivity, negative affect
      was assessed after viewing strongly aversive as well as neutral movie clips. Our
      results show increased gray matter volume in the dorsal part of the left amygdala
      during the premenstrual phase when compared with the late follicular phase. This
      volume increase was positively correlated with the premenstrual increase in
      stress-induced negative affect. This is the first study showing structural
      plasticity of the amygdala in humans at the macroscopic level that is associated
      with both endogenous gonadal hormone fluctuations and stress sensitivity. These
      results correspond with animal findings of gonadal hormone-mediated neural
      plasticity in the amygdala and have implications for understanding the
      pathogenesis of specific mood disorders associated with hormonal fluctuations.

PMID- 22162179
TI  - The nucleocytoplasmic conflict, a driving force for the emergence of plant
      organellar RNA editing.
AB  - RNA editing challenges the central dogma of molecular biology by changing the
      genetic information at the transcript level. In plant organelles, RNAs are
      modified by deamination of some specific cytosine residues, but the origin of
      this process remains puzzling. Different from the generally accepted neutral
      model to explain the emergence of RNA editing in plant organelles, we propose a
      new hypothesis based on the nucleocytoplasmic conflict theory. We assume that
      mutations in organellar genomes arose first and spread into the population
      provided they increased the transmission of their own maternally inherited
      genome. RNA editing appeared subsequently as a nuclear-encoded correction
      mechanism to restore the transmission of the nuclear genome. In plants, a well
      known consequence of the nucleocytoplasmic conflict is cytoplasmic male sterility
      (CMS) which is counteracted by the emergence of fertility restorer genes (Rf)
      belonging to the pentatricopeptide repeat (PPR) protein family. Interestingly,
      RNA-editing deficiency can lead to CMS, and it now clearly appears that PPR
      proteins are major players in RNA editing. This striking similarity between the
      mechanisms of fertility restoration and RNA editing can be explained if both
      reactions are the consequence of the same driving force, the nucleocytoplasmic
      conflict. Similarly, the prevalence of RNA editing in eukaryotic organellar
      genomes could also be a consequence of the genetic antagonism between organellar
      and nuclear genomes.

PMID- 22162180
TI  - Premature loss of bone remodeling compartment canopies is associated with
      deficient bone formation: a study of healthy individuals and patients with
      Cushing's syndrome.
AB  - A remarkable property of bone remodeling is that osteoblasts form bone matrix
      exactly where and when osteoclasts have removed it. The bone remodeling
      compartment (BRC) canopies that cover bone surfaces undergoing remodeling were
      proposed to be critical players in this mechanism. Here, we provide support to
      this hypothesis by analyzing the changes in prevalence of BRC canopies during the
      progress of the remodeling cycle in a cohort of healthy individuals and in
      patients with endogenous Cushing's syndrome (CS), and by relating these changes
      in prevalence with the extent of bone forming surfaces. Both cohorts showed
      almost 100% canopy coverage above resorbing osteoclasts, and only about 76% above
      bone forming surfaces. This indicates that BRC canopies are invariably associated
      with the early stage of the remodeling cycle, but may disappear later.
      Interestingly, in control and two-thirds of the CS patients, a significant
      decline in canopy coverage occurred only once bone formation was initiated, but
      in the remaining third of the CS patients the prevalence of canopies already
      decreased before bone formation. This canopy loss before initiation of bone
      formation coincided with significantly less bone-forming surface compared with
      canopy loss at a later stage. These observations support a model where bone
      restitution is compromised in the absence of BRC canopies, and apparently does
      not start when the BRC canopy is lost before initiation of the bone formation
      step. This model is discussed in the context of possible biological roles of BRC
      canopies. It suggests that BRC canopies could be privileged targets for treating
      patients suffering from a negative bone formation-resorption balance.

PMID- 22162181
TI  - Synthesis and functional characterization of tridegin and its analogues:
      inhibitors and substrates of factor XIIIa.
AB  - Tridegin, a 66-mer peptide isolated from the leech Haementeria ghilianii, is a
      potent inhibitor of the coagulation factor XIIIa. This paper describes the
      chemical synthesis of tridegin by two different strategies--solid-phase assembly
      and native chemical ligation--both followed by oxidation in solution phase.
      Tridegin and truncated analogues were examined for their activity and revealed a
      particular importance of the C-terminal region of the parent peptide. Based on
      these studies a minimal sequence required for factor XIIIa inhibition could be
      identified. Our data revealed that the glutamine residue at position 52 (Q52) of
      tridegin most likely binds to the active site of factor XIIIa and was therefore
      suggested to react with the enzyme. The function of the N-terminal region is also
      discussed, as the isolated C-terminal segment of tridegin lost its inhibitory
      activity rapidly in the presence of factor XIIIa, whereas this was not the case
      for the full-length inhibitor.

PMID- 22162183
TI  - Tendon impingement of the extensor digiti minimi: clinical cases series and
      cadaveric study.
AB  - The authors describe two unique clinical cases of closed extensor digiti minimi
      (EDM) tendon injuries after hyperflexion of the wrist with full finger flexion
      and one case of chronic tenosynovitis around the EDM tendon. All three cases were
      thought to be related to the bifurcation of the EDM tendon and synovial septum.
      Subsequently, variations in EDM tendons were investigated in 49 cadaveric hands
      with a focus on patterns of tendon bifurcation and their relationships with the
      surrounding synovial sheath. The EDM tendon was found to be bifurcated in 74% (n
      = 36) of hands and all of these hands contained a synovial septum. In 9 (25%)
      hands, the EDM tendon bifurcated proximal to the retinaculum, in 15 (42%), it
      bifurcated distal to the retinaculum, and in the other 12 hands (33%), the tendon
      bifurcated at the retinacular level. In 6 of the 15 hands with an
      infraretinacular bifurcation, the tendon was found to impinge on the synovial
      septum during passive flexion of the wrist with full finger flexion, and the mean
      distance between the synovial septum and the bifurcation point in these specimens
      was 0.6 cm (range, 0.4-0.7 cm), which was differed significantly from hands not
      showing impingement (P = 0.01). This study shows that distal bifurcation of the
      EDM tendon may lead to tendon impingement on the septum and suggests that this is
      a potential etiology of chronic tenosynovitis of the fifth compartment and of
      acute closed tendon injuries.

PMID- 22162182
TI  - Probing the frontiers of glycoprotein synthesis: the fully elaborated beta
      subunit of the human follicle-stimulating hormone.

PMID- 22162185
TI  - Catalytic selective oxyamidation of cyclic enamides using nitrenes.

PMID- 22162186
TI  - Diamond-shaped [Ag4]4+ cluster encapsulated by silicotungstate ligands: synthesis
      and catalysis of hydrolytic oxidation of silanes.

PMID- 22162184
TI  - Placebo effect characteristics observed in a single, international, longitudinal
      study in Huntington's disease.
AB  - BACKGROUND: Classically, clinical trials are based on the placebo-control design.
      Our aim was to analyze the placebo effect in Huntington's disease. METHODS:
      Placebo data were obtained from an international, longitudinal, placebo
      controlled trial for Huntington's disease (European Huntington's Disease
      Initiative Study Group). One-hundred and eighty patients were evaluated using the
      Unified Huntington Disease Rating Scale over 36 months. A placebo effect was
      defined as an improvement of at least 50% over baseline scores in the Unified
      Huntington Disease Rating Scale, and clinically relevant when at least 10% of the
      population met it. RESULTS: Only behavior showed a significant placebo effect,
      and the proportion of the patients with placebo effect ranged from 16% (first
      visit) to 41% (last visit). Nondepressed patients with better functional status
      were most likely to be placebo-responders over time. CONCLUSIONS: In Huntington's
      disease, behavior seems to be more vulnerable to placebo than overall motor
      function, cognition, and function

PMID- 22162187
TI  - Mesoscale integration in titania/J-aggregate hybrid nanofibers.

PMID- 22162189
TI  - A synthetic approach toward a self-regulated insulin delivery system.

PMID- 22162188
TI  - Identification of a novel biomarker gene set with sensitivity and specificity for
      distinguishing between allograft rejection and tolerance.
AB  - Here we examined whether the expression of a novel immunoregulatory gene set
      could be used to predict outcomes in murine models of rapamycin-induced cardiac
      tolerance, spontaneous hepatic tolerance, and cardiac rejection. The expression
      of the immunoregulatory gene set was assessed with the GeXP multiplex reverse
      transcription polymerase chain reaction (RT-PCR) analysis system, and it was
      correlated to the pathological and biochemical parameters of the allografts. In
      rejecting cardiac grafts, the increased expression of an inflammatory set of
      genes, which included CD45, CD4, CD25, suppressor of cytokine signaling 2,
      cytotoxic T lymphocyte-associated protein 4 (CTLA4), selectin lymphocyte,
      interferon-gamma (IFN-gamma), programmed cell death 1 (Pdcd1), and granzyme B
      (Gzmb), was seen 8 days after transplantation along with histological evidence of
      severe allograft rejection. In tolerant cardiac allografts, the expression of
      fibrinogen-like protein 2 (Fgl2), Pdcd1, killer cell lectin-like receptor G1
      (Klrg1), CTLA4, and lymphocyte-activation gene 3 was associated with tolerance.
      In a model of liver allograft tolerance, the increased expression of lectin
      galactose-binding soluble 1, Fgl2, CD39, phosphodiesterase 3B, Klrg1, forkhead
      box P3 (Foxp3), and transforming growth factor beta as well as the inflammatory
      set of genes was observed 8 to 14 days after transplantation (ie, when there was
      severe inflammatory injury). At a later time when the liver allografts had been
      fully accepted and were histologically normal, the expression of the inflammatory
      set of genes returned to the baseline, but the expression of the tolerogenic set
      of genes was still increased. Genes that were expressed in tolerant cardiac and
      liver allografts included Fgl2, Klrg1, and Foxp3, whereas genes associated with
      rejection included CD25, Gzmb, and IFN-gamma. Our data indicate that monitoring
      the graft expression of a novel biomarker gene set with the GeXP multiplex RT-PCR
      analysis system may allow differentiation between rejection and tolerance.

PMID- 22162190
TI  - Quantifying photoinitiation efficiencies in a multiphotoinitiated free-radical
      polymerization.
AB  - Online size exclusion chromatography-electrospray ionization-mass spectrometry
      (SEC/ESI-MS) is employed for quantifying the overall initiation efficiencies of
      photolytically generated radical fragments. In a unique experiment, we present
      the first quantitative and systematic study of methyl-substituted acetophenone
      type photoinitiators being employed in a single cocktail to initiate the free
      radical polymerization of methyl methacrylate (MMA) in bulk. The photoinitiators
      are constituted of a set of two known and four new molecules, which represent an
      increasing number of methyl substituents on their benzoyl fragment, that is,
      benzoin, 4-methylbenzoin, 2,4-dimethylbenzoin, 2,4,6-trimethylbenzoin, 2,3,5,6
      tetramethylbenzoin, and 2,3,4,5,6-pentamethylbenzoin. The absolute quantitative
      evaluation of the mass spectra shows a clear difference in the initiation ability
      of the differently substituted benzoyl-type radical fragments: Increasing the
      number of methyl substituents leads to a decrease in incorporation of the radical
      fragments.

PMID- 22162191
TI  - K-t sparse GROWL: sequential combination of partially parallel imaging and
      compressed sensing in k-t space using flexible virtual coil.
AB  - Because dynamic MR images are often sparse in x-f domain, k-t space compressed
      sensing (k-t CS) has been proposed for highly accelerated dynamic MRI. When a
      multichannel coil is used for acquisition, the combination of partially parallel
      imaging and k-t CS can improve the accuracy of reconstruction. In this work, an
      efficient combination method is presented, which is called k-t sparse Generalized
      GRAPPA fOr Wider readout Line. One fundamental aspect of this work is to apply
      partially parallel imaging and k-t CS sequentially. A partially parallel imaging
      technique using a Generalized GRAPPA fOr Wider readout Line operator is adopted
      before k-t CS reconstruction to decrease the reduction factor in a
      computationally efficient way while preserving temporal resolution. Channel
      combination and relative sensitivity maps are used in the flexible virtual coil
      scheme to alleviate the k-t CS computational load with increasing number of
      channels. Using k-t FOCUSS as a specific example of k-t CS, the experiments with
      Cartesian and radial data sets demonstrate that k-t sparse Generalized GRAPPA fOr
      Wider readout Line can produce results with two times lower root-mean-square
      error than conventional channel-by-channel k-t CS while consuming up to seven
      times less computational cost.

PMID- 22162192
TI  - Employee to employer communication skills: balancing cancer treatment and
      employment.
AB  - BACKGROUND: Cancer patients face difficulties in accessing legally mandated
      benefits and accommodations when they return to the workplace. Poor employer
      employee communication inflates these difficulties. Although proven methods to
      facilitate physician-patient communication exist, these have not been applied to
      the workplace. Thus, we aimed to assess the feasibility and utility of applying
      these methods to educate patients about their workplace rights and provide them
      with communication skills training to aid their conversations with their
      employers. METHODS: A DVD was produced to educate patients and facilitate
      workplace communication. Participants consisted of 28 solid tumor cancer patients
      (14 women and 14 men) who completed primary cancer treatment in the past 12
      months and were employed at the time of diagnosis. Participants watched a
      communication skills training DVD and completed a telephone interview. The
      interview elicited information about workplace experiences and evaluation of the
      DVD training program. RESULTS: The physician-patient communication skills
      training model utilized was successfully translated to the employer-employee
      setting. All but one participant found the DVD useful and easy to understand and
      indicated a high degree of confidence in using the communication skills to help
      them ask for workplace accommodations. All participants agreed that it would help
      newly diagnosed patients in discussions with their employers. CONCLUSION: Our
      data provides promising preliminary evidence that patient communication skills
      training can be applied to the workplace setting and is a welcomed aid to newly
      diagnosed cancer patients in their discussions with employers regarding the
      impact of treatment on their work performance and needs for accommodations.

PMID- 22162193
TI  - Unexpected strength and toughness in chitosan-fibroin laminates inspired by
      insect cuticle.
AB  - A material inspired by natural insect cuticle and composed of chitosan and
      fibroin is created. The material exhibits the strength of an aluminum alloy at
      half its weight, while being clear, biocompatible, biodegradable, and
      micromoldable. The bioinspired laminate exhibits strength and toughness that are
      ten times greater than the unstructured component blend and twice that of its
      strongest constituent.

PMID- 22162194
TI  - Interactions of dietary carotenoids with activated (singlet) oxygen and free
      radicals: potential effects for human health.
AB  - Molecular mechanisms associated with the anti-/pro-oxidative properties of
      carotenoids (CARs) are described in organic solvents, micro-heterogeneous
      environments and model lipid membranes and in cellular suspensions. Singlet
      oxygen is important in the skin and eye and CARs are efficient singlet oxygen
      (SO) quenchers with corresponding rate constants near diffusion controlled
      (typically app. 1010 M-1 s-1) with lycopene (LYC) exhibiting the most efficient
      quenching in organic solvents. However, in membrane environments there is little
      or no difference in the quenching efficiency between the dietary CARs.
      Furthermore, aggregation of CARs, particularly those in the macula (lutein and
      zeaxanthin), markedly reduces SO quenching efficiency. Free radical interactions
      with CARs leads to at least three processes, electron and hydrogen atom transfer
      and adduct formation. The most studied is electron transfer where the CAR loses
      an electron to become a radical cation. The reactivity/lifetime of such CAR
      radicals may lead to a switch from anti- to pro-oxidant behaviour of CARs. These
      reactions are related to CAR redox potentials with LYC being the lowest (most
      easily oxidised) allowing LYC to reduce/repair all other CAR radical cations and
      LYC 'sacrificed' where mixtures of CARs are present in oxidative environments.
      Such redox-controlled reactions may lead to deleterious as well as beneficial
      health effects.

PMID- 22162195
TI  - Graphene-coated fiber for solid-phase microextraction of triazine herbicides in
      water samples.
AB  - Graphene is a novel and interesting carbon material that could be used for the
      separation and purification of some chemical compounds. In this investigation,
      graphene was used as a novel fiber-coating material for the solid-phase
      microextraction (SPME) of four triazine herbicides (atrazine, prometon, ametryn
      and prometryn) in water samples. The main parameters that affect the extraction
      and desorption efficiencies, such as the extraction time, stirring rate, salt
      addition, desorption solvent and desorption time, were investigated and
      optimized. The optimized SPME by graphene-coated fiber coupled with high
      performance liquid chromatography-diode array detection (HPLC-DAD) was
      successfully applied for the determination of the four triazine herbicides in
      water samples. The linearity of the method was in the range from 0.5 to 200
      ng/mL, with the correlation coefficients (r) ranging from 0.9989 to 0.9998. The
      limits of detection of the method were 0.05-0.2 ng/mL. The relative standard
      deviations varied from 3.5 to 4.9% (n=5). The recoveries of the triazine
      herbicides from water samples at spiking levels of 20.0 and 50.0  ng/mL were in
      the range between 86.0 and 94.6%. Compared with two commercial fibers (CW/TPR, 50
      MUm; PDMS/DVB, 60 MUm), the graphene-coated fiber showed higher extraction
      efficiency. 

PMID- 22162196
TI  - A general palladium-catalyzed aminocarbonylation of phenols to primary benzamides
      via in situ generation of aryl nonaflates.

PMID- 22162197
TI  - Intergenerational instability in Huntington disease: extreme repeat changes among
      134 transmissions.

PMID- 22162198
TI  - Personalized cancer care: opportunities and challenges in pediatric neuro
      oncology.

PMID- 22162199
TI  - Design, synthesis and biological evaluation of Trypanosoma brucei trypanothione
      synthetase inhibitors.
AB  - Trypanothione synthetase (TryS) is essential for the survival of the protozoan
      parasite Trypanosoma brucei, which causes human African trypanosomiasis. It is
      one of only a handful of chemically validated targets for T. brucei in vivo. To
      identify novel inhibitors of TbTryS we screened our in-house diverse compound
      library that contains 62,000 compounds. This resulted in the identification of
      six novel hit series of TbTryS inhibitors. Herein we describe the SAR exploration
      of these hit series, which gave rise to one common series with potency against
      the enzyme target. Cellular studies on these inhibitors confirmed on-target
      activity, and the compounds have proven to be very useful tools for further study
      of the trypanothione pathway in kinetoplastids.

PMID- 22162201
TI  - DNA methylation contributes to the regulation of sclerostin expression in human
      osteocytes.
AB  - Sclerostin, encoded by the SOST gene, is a potent inhibitor of bone formation,
      produced by osteocytes, not by osteoblasts, but little is known about the
      molecular mechanisms controlling its expression. We aimed to test the hypothesis
      that epigenetic mechanisms, specifically DNA methylation, modulate SOST
      expression. We found two CpG-rich regions in SOST: region 1, located in the
      proximal promoter, and region 2, around exon 1. qMSP and pyrosequencing analysis
      of DNA methylation showed that region 2 was largely methylated in all samples
      analyzed. In contrast, marked differences were observed in region 1. Whereas the
      CpG-rich region 1 was hypermethylated in osteoblasts, this region was largely
      hypomethylated in microdissected human osteocytes. Bone lining cells showed a
      methylation profile between primary osteoblasts and osteocytes. Whereas SOST
      expression was detected at very low level or not at all by RT-qPCR in several
      human osteoblastic and nonosteoblastic cell lines, and human primary osteoblasts
      under basal conditions, it was dramatically upregulated (up to 1300-fold) by the
      demethylating agent AzadC. Experiments using reporter vectors demonstrated the
      functional importance of the region -581/+30 of the SOST gene, which contains the
      CpG-rich region 1. In vitro methylation of this CpG-island impaired nuclear
      protein binding and led to a 75 +/- 12% inhibition of promoter activity. In
      addition, BMP-2-induced expression of SOST was markedly enhanced in cells
      demethylated by AzadC. Overall, these results strongly suggest that DNA
      methylation is involved in the regulation of SOST expression during osteoblast
      osteocyte transition, presumably by preventing the binding of transcription
      factors to the proximal promoter. To our knowledge, our data provide first ever
      evidence of the involvement of DNA methylation in the regulation of SOST
      expression and may help to establish convenient experimental models for further
      studies of human sclerostin.

PMID- 22162200
TI  - Mechanism of DNA depurination by carcinogens in relation to cancer initiation.
AB  - Depurinating DNA adducts formed by aromatic hydrocarbons and catechol estrogen
      quinones play a major role in cancer initiation. Most of these adducts depurinate
      instantaneously, but some guanine adducts depurinate from DNA with half-lives of
      hours. We report here, that after 10 h at 37  degrees C, reaction of estradiol
      3,4-quinone (E(2)-3,4-Q) with ds-DNA to yield N7Gua and N3Ade adducts was
      complete and more efficient than with ss-DNA. When E(2)-3,4-Q reacted with t-RNA,
      no adducts were detected after 10 h, and the level of N3Ade and N7Gua adducts
      after 10 days was less than half that with ss-DNA after 10 h. Reaction of E(2)
      3,4-Q and dG yielded 4-OHE(2)-1-N7dG, which spontaneously depurinated to yield 4
      OHE(2)-1-N7Gua. To investigate the mechanism of depurination, E(2)-3,4-Q was
      reacted with carbocyclicdeoxyguanosine, in which the ring oxygen of the
      deoxyribose moiety is substituted with CH(2) , and depurination was observed. The
      results from this experiment demonstrate that the oxocarbenium ion mechanism
      plays the major role in depurination and provides the first experimental evidence
      for this mechanism. A newly discovered beta-elimination mechanism also plays a
      minor role in depurination. Understanding why the depurinating estrogen-DNA
      adducts come from DNA, and not from RNA, underscores the critical role that these
      adducts play in initiating cancer.

PMID- 22162203
TI  - Anatomical and functional overlap within the insula and anterior cingulate cortex
      during interoception and phobic symptom provocation.
AB  - The anterior insula and the dorsal anterior cingulate cortex (ACC) are regarded
      as key brain structures associated with the integration of perceived phobic
      characteristics of external stimuli and the perception of ones own body responses
      that leads to emotional feelings. To test to what extent the activity in these
      two brain structures anatomically and functionally overlap during phobic
      reactions and interoception, we submitted the same group of phobic participants
      (n = 29; either spider or blood-injection-injury (BII) phobics) and controls (n =
      17) to both type of experimental paradigms. Results showed that there was a clear
      anatomical overlap in the Blood Oxygen Level-Dependent (BOLD) responses within
      the anterior insula and ACC elicited during phobic symptom provocation and during
      interoceptive awareness. The activity within these two brain structures also
      showed to be correlated in the spider phobia group, but not in the BII phobic
      participants. Our results seem to support the idea that the activity within these
      two brain areas would be associated with the integration of perceived stimuli
      characteristics and bodily responses that lead to what we label as "fear."
      However, that seems not to be the case in BII phobia, where more research is
      needed in order to clarify to what extent that could be associated with the
      idiosyncratic physiological response that these patients present in front of
      phobic stimuli (i.e., drop in heart rate and blood pressure).

PMID- 22162204
TI  - Responsive vesicles from the self-assembly of crystalline-coil
      polyferrocenylsilane-block-poly(ethylene oxide) star-block copolymers.
AB  - We demonstrate the synthesis and characterization of star-shaped crystalline-coil
      block copolymers with four arms consisting of an inner block of poly(ethylene
      oxide) and an outer semicrystalline compartment of
      poly(ferrocenyldimethylsilane), [PEO(50) -b-PFDMS(35)](4). The materials were
      synthesized by transition-metal-catalyzed ring-opening polymerization of
      dimethylsila[1]ferrocenophane in the presence of silane-functionalized four-arm
      PEO stars as macroinitiators and they exhibited a moderate polydispersity
      (PDI?1.4). Self-assembly in mixtures of THF and different alcohols as selective
      solvents for the PEO block resulted in the formation of semicrystalline vesicles
      (ethanol, 1-butanol) or large, rather ill-defined, spherical structures
      (methanol). Further, both the rate of addition of the selective co-solvent and
      the overall solvent/non-solvent ratio drastically affected the size and stability
      of the self-assembled particles. We could also show that a photoacid generator,
      as a model for an active substance, can be encapsulated and the UV-induced
      generation of HCl resulted in a straightforward degradation of the organometallic
      vesicles.

PMID- 22162205
TI  - Opportunistic infections after liver transplantation in patients infected with
      human immunodeficiency virus.

PMID- 22162206
TI  - Chemistry: a panoply of arrows.

PMID- 22162207
TI  - A discrete five-coordinate Ni(III) complex resembling the active site of the
      oxidized form of nickel superoxide dismutase.

PMID- 22162208
TI  - beta-Carotene and lycopene affect endothelial response to TNF-alpha reducing
      nitro-oxidative stress and interaction with monocytes.
AB  - SCOPE: Cardiovascular disease (CVD) is associated with vascular oxidative
      imbalance and inflammation. Increased reactive oxygen species (ROS) generation is
      associated with a functional inactivation of nitric oxide (NO) due to the
      reaction with O2-, leading to peroxynitrite (ONOO-) formation and subsequent
      reduction in the beneficial effect of vascular NO bioavailability. Carotenoids'
      rich diets have been associated with decreased risk of CVD, but the underlying
      mechanism is still unknown. METHODS AND RESULTS: In human umbilical vein
      endothelial cells (HUVECs), both beta-carotene (BC) or lycopene (Lyc)
      significantly affected tumor necrosis factor-alpha (TNF-alpha)-induced
      inflammation, being associated with a significant decrease in the generation of
      ROS (spectrofluorometry) and nitrotyrosine (an index of ONOO- formation,
      cytofluorimetry), an increased NO/cGMP (cyclic guanosine monophosphate) levels
      (EIA), and a down-regulation of NF-kappaB-dependent adhesion molecule expression
      (Western blot and EMSA) and monocyte-HUVEC interaction (adhesion assay). Our
      results indicate that BC or Lyc treatment reduce the inflammatory response in TNF
      alpha-treated HUVECs. This is due to the redox balance protection and to the
      maintenance of NO bioavailability. CONCLUSION: Our observations provide
      background for a novel mechanism for carotenoids' anti-inflammatory activity in
      the vasculature and may contribute to a better understanding of the protective
      effects of carotenoid-rich diets against CVD risk.

PMID- 22162209
TI  - Myxoprincomide: a natural product from Myxococcus xanthus discovered by
      comprehensive analysis of the secondary metabolome.

PMID- 22162210
TI  - Posttraumatic stress disorder (PTSD) in survivors of Hodgkin's lymphoma:
      prevalence of PTSD and partial PTSD compared with sibling controls.
AB  - OBJECTIVES: Studies of posttraumatic stress disorder (PTSD) document a
      significant proportion of cancer survivors reporting severe posttraumatic stress
      symptoms, even when they do not meet full diagnostic criteria. However, few
      studies have directly examined the clinical significance of these 'partial PTSD'
      symptoms in survivors. This study aimed to investigate the prevalence of PTSD
      symptoms in a cohort of long-term survivors of Hodgkin's lymphoma (HL) and to
      explore the clinical relevance of the partial PTSD phenomenon by assessing
      impairment of function secondary to sub-threshold symptomatology. METHODS: The
      Posttraumatic Diagnostic Scale was completed by 105 HL survivors and 101 sibling
      controls. Survivors' age at time of participation ranged from 24 to 71 years, age
      at time of diagnosis ranged from 6 to 61 years, and the median time since
      diagnosis was 16 years (range = 7-34). RESULTS: Posttraumatic stress disorder
      prevalence was not significantly higher in HL survivors (13%) compared with
      sibling controls (6.9%, p = 0.098). However, a significantly larger proportion of
      survivors (35.2%) met criteria for partial PTSD compared with siblings (17.8%, p
      = 0.004). Moreover, the majority of the survivors with partial PTSD (86.5%)
      reported experiencing some functional impairment related to these posttraumatic
      stress symptoms. CONCLUSIONS: A significant number of HL survivors experience
      posttraumatic stress symptoms severe enough to result in functional impairment.
      This finding underscores the importance of future research detailing the
      psychological and functional outcomes in survivors with partial PTSD and of
      careful clinical practice that assesses for functional impairment secondary to
      partial PTSD symptomatology, in male and female survivors, even years after
      completion of therapy.

PMID- 22162211
TI  - Simultaneous measurement of cerebral blood flow and transit time with turbo
      dynamic arterial spin labeling (Turbo-DASL): application to functional studies.
AB  - A turbo dynamic arterial spin labeling method (Turbo-DASL) was developed to
      simultaneously measure cerebral blood flow (CBF) and blood transit time with high
      temporal resolution. With Turbo-DASL, images were repeatedly acquired with a
      spiral readout after small-angle excitations during pseudocontinuous arterial
      spin labeling and control periods. Turbo-DASL experiments at 9.4 T without and
      with diffusion gradients were performed on rats anesthetized with isoflurane or
      alpha-chloralose. We determined blood transit times from carotid arteries to
      cortical arterial vessels (TT(a) ) from data obtained without diffusion gradients
      and to capillaries (TT(c) ) from data obtained with diffusion gradients. Cerebral
      arterial blood volume (CBV(a) ) was also calculated. At the baseline condition,
      both CBF and CBV(a) in the somatosensory cortical area were 40-50% less in rats
      with alpha-chloralose than in rats with isoflurane, while TT(a) and TT(c) were
      similar for both anesthetics. Absolute CBF and CBV(a) were positively correlated,
      while CBF and TT(c) were slightly negatively correlated. During forepaw
      stimulation, CBF increase was 15 +/- 3% (n = 7) vs. 60 +/- 7% (n = 5), and CBV(a)
      increase was 19 +/- 9% vs. 46 +/- 17% under isoflurane vs. alpha-chloralose
      anesthesia, respectively; CBF vs. CBV(a) changes were highly correlated. However,
      TT(a) and TT(c) were not significantly changed during stimulation. Our results
      support that arterial CBV increase plays a major role in functional CBF changes.

PMID- 22162212
TI  - Energy-efficient dehumidification over hierachically porous metal-organic
      frameworks as advanced water adsorbents.

PMID- 22162215
TI  - Detection of cytochrome P450 substrates by using a small-molecule droplet array
      on an NADH-immobilized solid surface.
AB  - Seeing below the surface: A small-molecule droplet array platform on an NADH
      immobilized solid surface and a biotinylated acetophenone derivative were
      developed to identify the substrate candidates for soluble P450 enzymes of
      interest. This methodology is thought to be easily applicable to other class I
      P450 systems, including those that use NADPH as cofactor.

PMID- 22162214
TI  - Autoproteolytic fragments are intermediates in the oligomerization/aggregation of
      the Parkinson's disease protein alpha-synuclein as revealed by ion mobility mass
      spectrometry.
AB  - Gas-phase protein separation by ion mobility: With its ability to separate the
      Parkinson's disease protein alpha-synuclein and its autoproteolytic products
      despite the small concentrations of the latter-ion-mobility MS has enabled the
      characterization of intermediate fragments in in vitro oligomerization
      aggregation. In particular, a possible key fragment, the highly aggregating C
      terminal fragment, alphaSyn(72-140), has been revealed.

PMID- 22162216
TI  - Targeting zinc finger domains with small molecules: solution structure and
      binding studies of the RanBP2-type zinc finger of RBM5.
AB  - The RNA binding motif protein 5 (RBM5), also known as Luca15 or H37, is a
      component of prespliceosomal complexes that regulates the alternative splicing of
      several mRNAs, such as Fas and caspase-2. The RBM5 gene is located at the 2p21.3
      chromosomal region, which is strongly associated with lung cancer and many other
      cancers. Both increased and decreased levels of RBM5 can play a role in tumor
      progression. In particular, downregulation of rbm5 is involved in lung cancer and
      other cancers upon Ras activation, and, also, represents a molecular signature
      associated with metastasis in various solid tumors. On the other hand,
      upregulation of RBM5 occurs in breast and ovarian cancer. Moreover, RBM5 was also
      found to be involved in the early stage of the HIV-1 viral cycle, representing a
      potential target for the treatment of the HIV-1 infection. While the molecular
      basis for RNA recognition and ubiquitin interaction has been structurally
      characterized, small molecules binding this zinc finger (ZF) domain that might
      contribute to characterizing their activity and to the development of potential
      therapeutic agents have not yet been reported. Using an NMR screening of a
      fragment library we identified several binders and the complex of the most
      promising one, compound 1, with the RBM5 ZF1 was structurally characterized in
      solution. Interestingly, the binding mechanism reveals that 1 occupies the RNA
      binding pocket and is therefore able to compete with the RNA to bind RBM5 RanBP2
      type ZF domain, as indicated by NMR studies.

PMID- 22162218
TI  - Drug eluting stenting in bifurcation coronary lesions long-term results applying
      a systematic treatment strategy.
AB  - OBJECTIVES: To explore the long-term results following implantation of drug
      eluting stents (DES) in bifurcation lesions according to contemporary "real
      world" practice. BACKGROUND: Limited information is available on the long-term
      outcomes of patients with bifurcation lesions who are treated using DES. A
      systematic approach for bifurcation lesion management was applied, using either a
      "provisional" single stent technique or a dedicated two stents strategy according
      to the side-branch diameter and severity of its ostial stenosis. METHODS: Four
      hundred one consecutive patients underwent bifurcation percutaneous coronary
      intervention (PCI) using DES and were included in our prospective registry. All
      adverse events were recorded up to 2 years and distinguished according to the
      planned PCI strategy (e.g., one versus two stents technique). RESULTS: A planned
      two stents strategy was used in 141 patients (35% of patients). In 260 patients
      (65%), the planned treatment involved stenting of the main branch only with
      "provisional" stenting of the side-branch according to procedural course. Thus,
      24 patients (9.2%) needed additional stenting at the side-branch to complete the
      PCI. Cumulative major adverse cardiac event rate at 1 and 2 years was similar for
      both groups (11.4% vs. 14.8% at 1 year and 19.4% vs. 25.7% at 2 years for the
      single vs. two stents groups, accordingly, P = NS for both). Likewise, there was
      no difference in mortality, cardiac mortality, myocardial infarction, need for
      target lesions or target vessel revascularization, or definite stent thrombosis
      rate between the two groups at 6, 12, and 2 years follow-up. The rate of
      angiographically confirmed (i.e., definite) stent thrombosis did not differ
      between the two groups during follow-up. CONCLUSIONS: Our study revealed
      favorable long-term clinical results following DES implantation using a
      systematic, rather simplified approach towards bifurcation stenting and using
      either a single or double stenting technique.

PMID- 22162219
TI  - Miniaturized matrix solid-phase dispersion combined with ultrasound-assisted
      dispersive liquid-liquid microextraction for the determination of three
      pyrethroids in soil.
AB  - A simple and miniaturized pretreatment procedure combining matrix solid-phase
      dispersion (MSPD) with ultrasound-assisted dispersive liquid-liquid
      microextraction (UA-DLLME) technique was proposed in first time for simultaneous
      determination of three pyrethroids (fenpropathrin, cyhalothrin and fenvalerate)
      in soils. The solid samples were directly extracted using MSPD procedure, and the
      eluent of MSPD was used as the dispersive solvent of the followed DLLME procedure
      for further purification and enrichment of the analytes before GC-ECD analysis.
      Good linear relationships were obtained for all the analytes in a range of 5.0
      500.0 ng/g with LOQs (S/N=10) ranged from 1.51 to 3.77 ng/g. Average recoveries
      at three spiked levels were in a range of 83.6-98.5% with RSD<=7.3%. The present
      method combined the advantages of MSPD and DLLME, and was successfully applied
      for the determination of three pyrethroids in soil samples. 

PMID- 22162221
TI  - Collagen-immobilized patch for repairing small tympanic membrane perforations: in
      vitro and in vivo assays.
AB  - Tympanic membrane (TM) perforation is still one of the most common otology
      complications. New designs of biomaterials, and lately tissue-engineered
      composites and grafts, have thoroughly revolutionized the management of TM
      perforation. In this study, we examined a biologically modified collagen
      immobilized polydimethyl siloxane patch to repair TM perforation. In vitro
      potential of the aforementioned patch as a scaffold to support fibroblast cell
      growth and adhesion was assessed. An in vivo assay of the patch for initiating
      repair of TM perforations also was investigated. In vitro assay showed that the
      patch has significantly increased cell adhesion and growth in comparison with
      unmodified ones (p < 0.05). In vivo study also showed an overall closure rate of
      TM perforation of 70% and an average gain of 15.75 +/- 4.29 dB in air-bone gap.
      This study shows that the preliminary in vivo evaluation of a modified siloxane
      patch in humans had promising results and is comparable to existing biomaterial
      patches.

PMID- 22162220
TI  - Effects of designed PLLA and 50:50 PLGA scaffold architectures on bone formation
      in vivo.
AB  - Biodegradable porous scaffolds have been investigated as an alternative approach
      to current metal, ceramic, and polymer bone graft substitutes for lost or damaged
      bone tissues. Although there have been many studies investigating the effects of
      scaffold architecture on bone formation, many of these scaffolds were fabricated
      using conventional methods such as salt leaching and phase separation, and were
      constructed without designed architecture. To study the effects of both designed
      architecture and material on bone formation, this study designed and fabricated
      three types of porous scaffold architecture from two biodegradable materials,
      poly (L-lactic acid) (PLLA) and 50:50 Poly(lactic-co-glycolic acid) (PLGA), using
      image based design and indirect solid freeform fabrication techniques, seeded
      them with bone morphogenetic protein-7 transduced human gingival fibroblasts, and
      implanted them subcutaneously into mice for 4 and 8 weeks. Micro-computed
      tomography data confirmed that the fabricated porous scaffolds replicated the
      designed architectures. Histological analysis revealed that the 50:50 PLGA
      scaffolds degraded but did not maintain their architecture after 4 weeks
      implantation. However, PLLA scaffolds maintained their architecture at both time
      points and showed improved bone ingrowth, which followed the internal
      architecture of the scaffolds. Mechanical properties of both PLLA and 50:50 PLGA
      scaffolds decreased but PLLA scaffolds maintained greater mechanical properties
      than 50:50 PLGA after implantation. The increase of mineralized tissue helped
      support the mechanical properties of bone tissue and scaffold constructs between
      4-8 weeks. The results indicate the importance of choice of scaffold materials
      and computationally designed scaffolds to control tissue formation and mechanical
      properties for desired bone tissue regeneration.

PMID- 22162222
TI  - Chronological change from face-on to edge-on ordering of zinc
      tetraphenylporphyrin at the phenyloctane-highly oriented pyrolytic graphite
      interface.
AB  - The self-assembled structure of alkoxy- and N-alkylcarbamoyl-substituted zinc
      tetraphenylporphyrin at the liquid-highly oriented pyrolytic graphite (HOPG)
      interface was observed by using scanning tunneling microscopy. The alkoxy
      porphyrin showed a phase transition from face-on to edge-on ordering. The phase
      transition requires the close-packed structure of alkoxy porphyrin. The
      chronological change of the ordering was traced to show the existence of several
      types of Ostwald ripening including two-step phase transition from small edge-on
      to face-on and then further to edge-on orderings. On the other hand, the N
      alkylcarbamoyl porphyrin showed persistent edge-on ordering, and the ordering was
      analyzed by the Moire pattern. Although the edge-on ordering is observed only in
      the nonpolar solvent, the orderings have potential applications in the charge and
      energy transfer.

PMID- 22162223
TI  - Behcet's disease: successful treatment with infliximab in 7 patients with severe
      vascular manifestations. A retrospective analysis.
AB  - OBJECTIVE: To evaluate the therapeutic effect of infliximab in patients with
      inflammatory vascular lesions due to Behcet's disease (BD). METHODS: Seven
      patients with clinical evidence of severe vascular BD were analyzed: 3 patients
      with aortic involvement, 1 with recurrent venous thrombosis of the pelvic veins,
      1 with recurrent venous and arterial thromboses of the thigh, and 2 with retinal
      vasculitis. Infliximab was initiated with 3-5 mg/kg of body weight and infusions
      were repeated in intervals of 4 weeks as either first-line therapy in 3 patients
      or add on after failure of conventional immunosuppression in the remaining 4.
      Ongoing immunosuppression consists of a various combination of azathioprine (n =
      2), methotrexate (n = 3), cyclosporine (n = 3), and low-dose glucocorticoids (n =
      3). RESULTS: Control of inflammation was seen 1-5 days after infliximab induction
      in all patients. C-reactive protein level was reduced from a mean of 89 mg/liter
      prior to infliximab to 9 mg/liter thereafter. Vision increased rapidly in
      patients with retinal vasculitis. Vascular grafts remained patent. The inflamed
      and dissected aortic wall healed over a period of 6 months. Infliximab could be
      stopped in 2 patients; intervals could be extended in 4 to a maximum of 8 weeks.
      Infliximab and basic immunosuppression were well tolerated; no drug-induced side
      effects were recorded. CONCLUSION: Infliximab is effective in inducing and
      maintaining remission of vasculitic activity in patients with BD. The rapid
      effect together with excellent tolerability suggests that infliximab should be
      considered as a first-line agent in severe vascular BD.

PMID- 22162224
TI  - APC as a mobile scaffold: regulation and function at the nucleus, centrosomes,
      and mitochondria.
AB  - Genetic mutations of adenomatous polyposis coli (APC) predispose to high risk of
      human colon cancer. APC is a large tumor suppressor protein and truncating
      mutations disrupt its normal roles in regulating cell migration, DNA
      replication/repair, mitosis, apoptosis, and turnover of oncogenic beta-catenin.
      APC is targeted to multiple subcellular sites, and here we discuss recent
      evidence implicating novel protein interactions and functions of APC in the
      nucleus and at centrosomes and mitochondria. The ability of APC to shuttle
      between these and other cell locations is hypothesized to be integral to its
      cellular function.

PMID- 22162225
TI  - Exercise for all?

PMID- 22162226
TI  - Carcinogenesis of pancreatic cancer: challenges, collaborations, progress.

PMID- 22162227
TI  - Pancreatic cancer: overview of descriptive epidemiology.
AB  - Pancreatic cancer mortality rates have been increasing in high-income countries
      between the 1950s and the 1980s, and have leveled off or declined thereafter,
      particularly in men. To provide a global overview of recent pancreatic cancer
      mortality, we analyzed official death of the world certification data derived
      from the World Health Organization for 35 European countries and 19 other
      countries over the period 1980-2007. In 2007, the highest mortality rates from
      pancreatic cancer were in the Baltic countries, and some central/eastern and
      northern European countries (over 9.5/100 000 men and 6/100 000 women), whereas
      the lowest ones were in Latin America and Hong Kong (below 5/100 000 men and
      3/100 000 women). Japan, the USA, Russia and the European Union (EU), as well as
      the largest countries in the EU, had rates around 7-9/100 000 men and 5-6/100 000
      women. In the early 2000s, rates have been approximately stable in many European
      countries, as in the USA, Japan, and Australia. In Nordic countries and the UK,
      where declines in rates have been observed between the 1980s and the 1990s,
      mortality from pancreatic cancer has tended to rise over most recent calendar
      years. Some persisting rises were still found in men from a few countries of
      southern and central/eastern Europe (with low rates in the past), as well as in
      the EU overall, and in women from European and Asian countries. Recent trends
      were generally more favorable in young adults (30-49 yr), suggesting that overall
      trends are likely to improve in the near future.

PMID- 22162228
TI  - Genetic susceptibility to pancreatic cancer.
AB  - Pancreatic cancer is the fourth leading cause of cancer death in both men and
      women in the United States. However, it has the poorest prognosis of any major
      tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking,
      increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes
      mellitus have all been demonstrated to increase risk of pancreatic cancer. A
      family history of pancreatic cancer has also been associated with increased risk
      suggesting inherited genetic factors also play an important role, with
      approximately 5-10% of pancreatic cancer patients reporting family history of
      pancreatic cancer. While the genetic basis for the majority of the familial
      clustering of pancreatic cancer remains unclear, several important pancreatic
      cancer genes have been identified. These consist of high penetrance genes
      including BRCA2 or PALB2, to more common genetic variation associated with a
      modest increase risk of pancreatic cancer such as genetic variation at the ABO
      blood group locus. Recent advances in genotyping and genetic sequencing have
      accelerated the rate at which novel pancreatic cancer susceptibility genes have
      been identified with several genes identified within the past few years. This
      review addresses our current understanding of the familial aggregation of
      pancreatic cancer, established pancreatic cancer susceptablity genes and how this
      knowledge informs risk assessment and screening for high-risk families.

PMID- 22162230
TI  - Epidemiology and potential mechanisms of tobacco smoking and heavy alcohol
      consumption in pancreatic cancer.
AB  - Tobacco smoking represents an important known cause of ductal pancreatic
      adenocarcinoma. Recent data from pooled analyses in consortia involving multiple
      case-control and cohort studies suggest that heavy (but not moderate or light)
      alcohol consumption also may increase pancreatic cancer risk. Animal and human
      evidence indicate that tobacco carcinogens and metabolites may act in concert and
      have both genetic and epigenetic effects at early and later stages in pancreatic
      tumorigenesis. One of the more important tobacco-related carcinogens, NNK,
      probably acts via multiple pathways. Heavy alcohol consumption may increase
      pancreatic cancer risk by potentiating the effects of other risk factors such as
      tobacco smoking, poor nutrition, and inflammatory pathways related to chronic
      pancreatitis, but also may have independent genetic and epigenetic effects.
      Animal and human studies of tobacco- and alcohol-related pancreatic
      carcinogenesis suggest multi-modal, overlapping mechanistic pathways. Tobacco
      smoking and heavy alcohol consumption are preventable exposures, and their
      avoidance would substantially decrease the burden of pancreatic cancer worldwide.

PMID- 22162229
TI  - Aberrant signaling pathways in pancreatic cancer: a two compartment view.
AB  - Pancreatic cancer is a devastating disease with historically limited success in
      treatment and a poor prognosis. Pancreatic cancer appears to have a progressive
      pathway of development, initiating from well-described pancreatic intraepithelial
      neoplasia lesions and concluding with invasive carcinoma. These early lesions
      have been shown to harbor-specific alterations in signaling pathways that remain
      throughout this tumorigenesis process. Meanwhile, new alterations occur during
      this process of disease progression to have a cumulative effect. This series of
      events not only impacts the epithelial cells comprising the tumor, but they may
      also affect the surrounding stromal cells. The result is the formation of complex
      signaling networks of communication between the tumor epithelial cell and the
      stromal cell compartments to promote a permissive and cooperative environment.
      This article highlights some of the most common pathway aberrations involved with
      this disease, and how these may subsequently affect one or both cellular
      compartments. Consequently, furthering our understanding of these pathways in
      terms of their function on the tumoral epithelial and stromal compartments may
      prove to be crucial to the development of targeted and more successful therapies
      in the future.

PMID- 22162231
TI  - Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic
      mechanisms.
AB  - In the United States, pancreatic cancer is characterized by a low 5-yr survival
      rate of approximately 6%, fewer than 10% of patients diagnosed with localized
      disease and thus candidates for "curative" surgical resection, increasing
      incidence and few established risk factors. Similar statistics are observed for
      other industrialized nations. With new evidence to suggest that pancreatic cancer
      develops over a number of years, markers that can better identify high risk
      patients and are applicable to earlier diagnosis hold promise for improving these
      dire statistics. Obesity is one of the few modifiable risk factors that has been
      associated with increased risk of pancreatic cancer and also is related to
      increased risk of diabetes, a condition that in turn has been associated with
      pancreatic cancer development. Given recent data that nearly 70% of United States
      adults are overweight or obese, a clarification of the complex association
      between obesity and pancreatic cancer may disclose targets for prevention and
      intervention to decrease incidence and improve prognosis of this highly fatal
      disease. An overview of the current epidemiology and hypothesized biological
      mechanisms involved in the obesity-pancreatic cancer association are presented.

PMID- 22162233
TI  - Selected medical conditions and risk of pancreatic cancer.
AB  - We review the current evidence for associations of several medical conditions
      with risk of pancreatic cancer, including allergies, pancreatitis, gall bladder
      disease, cholecystectomy, ulcers, gastrectomy, appendectomy, and tonsillectomy.
      There are consistent findings of reduced risk associated with presence of self
      reported allergies, particularly hay fever but not asthma; data on other
      allergies are limited and inconclusive. Several studies provide evidence that
      patients with pancreatic cancer are more likely than comparison groups to report
      pancreatitis. Those studies that investigated the time between onset of
      pancreatitis and diagnosis of pancreatic cancer found that risk estimates
      declined with longer periods of time; however, increased risks were noted for
      long-term pancreatitis, indicating that this condition is both a risk factor and
      a sign of early disease. Increased risk was reported in association with
      cholelithiasis, but the few studies that considered time before diagnosis of
      cancer did not find increased risk for cholelithiasis diagnosed in the more
      distant past. There is weak evidence that cholecystectomy 2 or more years before
      cancer diagnosis is related to risk, but this is based on only a few studies.
      There is no consistent association between ulcers and risk, while gastrectomy may
      increase risk. Overall, study of these conditions, particularly those that are
      rare, presents methodologic challenges. Time between diagnoses is likely to be
      important but is not considered in most studies. Lack of adequate control in
      several studies for risk factors such as smoking and heavy alcohol use also makes
      it difficult to draw firm conclusions about these results.

PMID- 22162232
TI  - Diabetes and pancreatic cancer.
AB  - Type 2 diabetes mellitus is likely the third modifiable risk factor for
      pancreatic cancer after cigarette smoking and obesity. Epidemiological
      investigations have found that long-term type 2 diabetes mellitus is associated
      with a 1.5-fold to 2.0-fold increase in the risk of pancreatic cancer. A causal
      relationship between diabetes and pancreatic cancer is also supported by findings
      from prediagnostic evaluations of glucose and insulin levels in prospective
      studies. Insulin resistance and associated hyperglycemia, hyperinsulinemia, and
      inflammation have been suggested to be the underlying mechanisms contributing to
      development of diabetes-associated pancreatic cancer. Signaling pathways that
      regulate the metabolic process also play important roles in cell proliferation
      and tumor growth. Use of the antidiabetic drug metformin has been associated with
      reduced risk of pancreatic cancer in diabetics and recognized as an antitumor
      agent with the potential to prevent and treat this cancer. On the other hand, new
      onset diabetes may indicate subclinical pancreatic cancer, and patients with new
      onset diabetes may constitute a population in whom pancreatic cancer can be
      detected early. Biomarkers that help define high-risk individuals for clinical
      screening for pancreatic cancer are urgently needed. Why pancreatic cancer causes
      diabetes and how diabetes affects the clinical outcome of pancreatic cancer have
      yet to be fully determined. Improved understanding of the pathological mechanisms
      shared by diabetes and pancreatic cancer would be the key to the development of
      novel preventive and therapeutic strategies for this cancer.

PMID- 22162234
TI  - Occupational risk factors and pancreatic cancer: a review of recent findings.
AB  - Several occupational exposures have been linked to excess risk of pancreatic
      cancer; however, most associations are not well established. The objective of
      this review article is to report on the more recently published studies (1998
      2010), and provide a summary of the most consistently reported occupational risk
      factors for pancreatic cancer, including exposure to chlorinated hydrocarbon
      compounds, pesticides, polycyclic aromatic hydrocarbons (PAHs), metals,
      nitrosamines, radiation, various airborne particles, and employment in sedentary
      occupations. We conclude that the strongest and most consistent findings linking
      occupational exposures with pancreatic cancer risk to date are for chlorinated
      hydrocarbons and PAHs.

PMID- 22162235
TI  - Pancreatic cancer: Helicobacter pylori colonization, N-nitrosamine exposures, and
      ABO blood group.
AB  - Thirty years of research with animal models has shown that pancreatic
      adenocarcinoma is induced by N-nitrosamine carcinogens, which damage DNA through
      adduct formation. Human risk factors for pancreatic cancer include gastric
      colonization by Helicobacter pylori, as well as dietary intake of those same N
      nitrosamines or of nitrite which forms those N-nitrosamines in the stomach, and
      cigarette smoking which also contains those N-nitrosamines. Physiologic actions
      of H. pylori colonization enhance the carcinogenic effect of N-nitrosamines
      delivered by smoking or dietary sources. This effect is modulated by host
      inflammatory response to the organism, by various virulence and other properties
      of the Helicobacter itself, and by host-organism interactions. A recent genome
      wide association study identified SNPs within the ABO 9q34 locus as statistically
      significantly associated with risk of pancreatic cancer. A number of recent and
      older studies going back 40 yr also support the ABO association. ABO-product
      antigens are expressed on gastrointestinal epithelium on which H. pylori binds,
      and ABO genotype is known to be associated with risks of duodenal and gastric
      ulcer and with risk of gastric cancer, conditions definitively related to
      Helicobacter colonization. We suspect that ABO genotype/phenotype status
      influences the behavior of H. pylori which in turn affects gastric and pancreatic
      secretory function, and these ultimately influence the pancreatic carcinogenicity
      of dietary- and smoking-related N-nitrosamine exposures, and thus risk of
      pancreatic cancer. Our study results on the interaction of ABO and H. pylori
      significantly confirm this hypothesis and together with other existing studies
      strongly implicate this organism in the disease etiology.

PMID- 22162236
TI  - Is dietary fat, vitamin D, or folate associated with pancreatic cancer?
AB  - Although potentially modifiable risk factors for pancreatic cancer include
      smoking, obesity, and diabetes, less is known about the extent to which diet
      affects cancer risk. Recent studies have demonstrated some consistency for
      dietary fat being associated with elevated pancreatic cancer risk, particularly
      from animal sources. However, less is known about which fatty acids pose the
      greatest risk. Vitamin D, due to its endogenous production following UV-B
      exposure, is a unique risk factor in that researchers have created several
      methods to assess its exposure in humans. Studies that measured vitamin D
      exposure differently have shown inconsistent results. Dietary studies suggest
      protective associations, whereas studies of circulating 25-hydroxyvitamin D
      status show null or positive associations with low or very high concentrations,
      respectively. Several, but not all epidemiologic studies provide evidence of an
      inverse relationship between total and/or dietary folate and risk of pancreatic
      cancer. Protective associations for circulating folate are more often observed
      among populations with inadequate status. This article reviews the current
      epidemiological and experimental evidence investigating the relationship of
      dietary fat, vitamin D, and folate with pancreatic cancer. Additionally the
      mechanisms by which these risk factors may contribute to cancer, the
      methodological challenges involved with assessing risk, and other obstacles
      encountered when ascertaining the magnitude and direction of these three
      exposures are discussed.

PMID- 22162237
TI  - Pancreatic cancer risk: associations with meat-derived carcinogen intake in the
      Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort.
AB  - BACKGROUND: Epidemiological studies report positive associations between high
      temperature cooked meat intake and pancreatic cancer. We assessed associations
      between dietary intake of heterocyclic amines (HCAs) and benzo(a)pyrene (BaP)
      mutagens formed in meat cooked at high temperatures-and incident exocrine
      pancreatic cancer in a prospective cohort. METHODS: The 62 581 subjects
      randomized to screening in the Prostate, Lung, Colorectal, and Ovarian Screening
      Trial (PLCO) who completed an initial dietary survey that assessed meat intake,
      cooking methods, and doneness preferences defined the cohort. Subjects were
      surveyed annually for incident cancers through 2007. A National Cancer Institute
      research database (CHARRED) was used to estimate HCA and BaP intake and a
      Mutagenic Activity Index (MAI) from survey data. Proportional hazard ratios (HRs)
      for risk of pancreatic cancer were estimated from multi-variate Cox regression
      models by quintile of intake, with the lowest quintile as the referent. RESULTS:
      During follow-up (median: 10 yr), 248 cases of exocrine pancreatic cancer were
      confirmed. Preferences for well and very well done meat were generally associated
      with increased risks. Significant elevations in pancreatic cancer risk were found
      in upper quintiles of MAI, and individual mutagens 2-amino-3,4,8
      trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx). Compared to the lowest quintile of MAI, the third and
      fifth quintiles brought HRs of 1.86 (1.22, 2.85) and 1.87 (1.16, 3.02),
      respectively. These three exposures exhibited significant (P-trend: 0.01-0.03)
      positive trends in risk as their levels increased CONCLUSION: Consuming well-done
      meat cooked at high temperatures, which contains high mutagen levels, appears to
      confer increased risk of pancreatic cancer.

PMID- 22162238
TI  - Honeycomb micropatterning of proteins on polymer films through the inverse
      microemulsion approach.
AB  - Here we report the rapid and convenient patterning of proteins on porous polymer
      film using the inverse microemulsion approach. Following this method, proteins,
      which were dissolved in water, were transferred into dichloromethane solution of
      polymers through the formation of inverse microemulsion by mixing the two
      solutions. The protein-containing microemulsion droplets accumulated
      automatically into large and stable ones on the surface of organic solution
      casting on solid substrates, and formed tightly packed microemulsion droplet
      arrays driven by surface tension. With the evaporation of organic solvent and
      water, the microemulsion droplet arrays, which act as the template, turn to
      honeycomb patterned pores bearing proteins in them. The formed protein patterns
      can be locally applied for the detection of other proteins through specific
      recognition. The generality and reproducibility for the formation of BSA/PS
      microporous film and protein patterning by using different polymers and solvents
      were demonstrated by investigating surfactant addition, polymer and solvent
      types, and casting volume on the morphology of the microporous films. A
      preliminary mechanism for the protein patterning is discussed based on the
      analysis of the experimental results.

PMID- 22162239
TI  - Bioinspired five-coordinate iron(III) complexes for stabilization of phenoxyl
      radicals.

PMID- 22162240
TI  - Exploiting the electrophilic properties of indole intermediates: new options in
      designing asymmetric reactions.

PMID- 22162241
TI  - Design, synthesis, evaluation, and structure of vitamin D analogues with furan
      side chains.
AB  - Based on the crystal structures of human vitamin D receptor (hVDR) bound to
      1alpha,25-dihydroxy-vitamin D(3) (1,25 D) and superagonist ligands, we previously
      designed new superagonist ligands with a tetrahydrofuran ring at the side chain
      that optimize the aliphatic side-chain conformation through an entropy benefit.
      Following a similar strategy, four novel vitamin D analogues with aromatic furan
      side chains (3a, 3b, 4a, 4b) have now been developed. The triene system has been
      constructed by an efficient stereoselective intramolecular cyclization of an enol
      triflate (A-ring precursor) followed by a Suzuki-Miyaura coupling of the
      resulting intermediate with an alkenyl boronic ester (CD-side chain, upper
      fragment). The furan side chains have been constructed by gold chemistry. These
      analogues exhibit significant pro-differentiation effects and transactivation
      potency. The crystal structure of 3a in a complex with the ligand-binding domain
      of hVDR revealed that the side-chain furanic ring adopts two conformations.

PMID- 22162242
TI  - Optimization and validation of a fast ultrahigh-pressure liquid chromatographic
      method for simultaneous determination of selected sulphonamides in water samples
      using a fully porous sub-2 MUm column at elevated temperature.
AB  - High temperature in HPLC is considered a valuable tool helping to overcome the
      increase in the column backpressure when using small packing particles such as
      sub-2 MUm, as it allows reduction in the mobile-phase viscosity. In this study, a
      fast analytical method based on HPLC-UV was developed using a sub-2 MUm column at
      elevated temperature for the simultaneous determination of nine sulphonamides.
      Owing to the lower viscosity of the mobile phase, the separation could be
      achieved in 3 min at 60 degrees C for all analytes. The effect of temperature,
      the organic modifier percentage and the flow rate on the retention time was
      studied. The method developed was used for the determination of selected
      sulphonamides in surface and wastewater samples. Sample preparation was carried
      out by solid-phase extraction on Oasis HLB cartridges. The method developed was
      validated based on the linearity, precision, accuracy, detection and
      quantification limits. The recovery ranged from 70.6 to 96 % with standard
      deviations not higher than 4.7%, except for sulphanilamide. Limits of detection
      ranged from 1 to 10 MUg/L after optimization of all analytical steps. This method
      has the highest performance in terms of analytical speed compared with other
      published HPLC-UV methods for the determination of sulphonamides in water. 

PMID- 22162243
TI  - Electrolysis of water in the diffusion layer: first-principles molecular dynamics
      simulation.
AB  - With Car-Parrinello molecular dynamics simulations the elementary reaction steps
      of the electrolysis of bulk water are investigated. To simulate the reactions
      occurring near the anode and near the cathode, electrons are removed or added,
      respectively. The study focuses on the reactions in pure water. Effects depending
      on a particular electrode surface or a particular electrolyte are ignored. Under
      anodic conditions, the reaction continues till molecular oxygen is formed, under
      cathodic conditions the formation of molecular hydrogen is observed. In addition
      the formation of hydrogen peroxide is observed as an intermediate of the anodic
      reaction. The simulations demonstrate that the electrochemistry of oxygen
      formation without direct electrode contact can be explained by radical reactions
      in a solvent. These reactions may involve the intermediate formation of ions. The
      hydrogen formation is governed by rapid proton transfers between water molecules.

PMID- 22162244
TI  - Nonhematopoietic cells are the primary source of bone marrow-derived lung
      epithelial cells.
AB  - Previous studies have demonstrated that bone marrow (BM)-derived cells
      differentiate into nonhematopoietic cells of multiple tissues. To date, it
      remains unknown which population(s) of BM cells are primarily responsible for
      this engraftment. To test the hypothesis that nonhematopoietic stem cells in the
      BM are the primary source of marrow-derived lung epithelial cells, either wild
      type hematopoietic or nonhematopoietic BM cells were transplanted into irradiated
      surfactant-protein-C (SPC)-null mice. Donor-derived, SPC-positive type 2
      pneumocytes were predominantly detected in the lungs of mice receiving purified
      nonhematopoietic cells and were absent from mice receiving purified hematopoietic
      stem and progenitor cells. We conclude that cells contained in the
      nonhematopoietic fraction of the BM are the primary source of marrow-derived lung
      epithelial cells. These nonhematopoietic cells may represent a primitive stem
      cell population residing in adult BM.

PMID- 22162245
TI  - The postprandial inflammatory response after ingestion of heated oils in obese
      persons is reduced by the presence of phenol compounds.
AB  - SCOPE: Heating during the process of cooking alters the chemical properties of
      foods and may affect subsequent postprandial inflammation. We tested the effects
      of four meals rich in different oils subjected to heating on the postprandial
      inflammatory metabolism of peripheral blood mononuclear cells (PBMCs). METHODS
      AND RESULTS: Twenty obese participants received four breakfasts following a
      randomized crossover design, consisting of milk and muffins made with different
      oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixture of seeds oil
      (SFO/canola oil) with added either dimethylpolysiloxane (SOD), or natural
      antioxidants from olive mill wastewater alperujo (phenols; SOP)), previously
      subjected to 20 heating cycles. Postprandial inflammatory status in PBMCs was
      assessed by the activation of nuclear NF-kappaB, the concentration in cytoplasm
      of the NF-kappaB inhibitor (IkappaB-alpha), the mRNA levels of NF-kappaB subunits
      and activators (p65, IKKbeta, and IKKalpha) and other inflammatory molecules (TNF
      alpha, IL-1beta, IL-6, MIF, and JNK), and lipopolysaccharide (LPS) levels. VOO
      and SOP breakfasts reduced NF-kappaB activation, increased IkappaB-alpha, and
      decreased LPS plasma concentration. SFO increased IKKalpha, IKKbeta, p65, IL-1b,
      IL-6, MIF, and JNK mRNA levels, and plasma LPS. CONCLUSION: Oils rich in phenols,
      whether natural (VOO) or artificially added (SOP), reduce postprandial
      inflammation, compared with seed oil (sunflower).

PMID- 22162246
TI  - Fine-tuning the pi-pi aromatic interactions in peptides: somatostatin analogues
      containing mesityl alanine.

PMID- 22162247
TI  - Indications for radiotherapy after neck dissection.
AB  - Up-front surgery and postoperative radiotherapy constitute a well-recognized
      treatment concept for locally or regionally advanced squamous cell carcinoma of
      the head and neck. This "treatment package" is further intensified with the
      concomitant application of chemotherapy during irradiation when high-risk
      features (ie, microscopically involved resection margins, extracapsular extension
      of the tumor from neck nodes, the presence of soft tissue deposits) are found on
      histopathologic examination of a resected specimen. With regard to neck disease,
      however, the demarcation line between low- and higher-risk clinical situations,
      which would differ with respect to the need for postoperative radiotherapy, is
      not clear. In an attempt to define the low-risk characteristics of disease in the
      neck that do not require adjuvant irradiation, we reviewed the available
      literature reports for any direct or indirect evidence on the value of
      postoperative radiotherapy in various clinical scenarios. The number of positive
      lymph nodes found in a dissected tissue specimen that should be used as a "cut
      off" point for introduction of postoperative radiotherapy was evaluated in the
      context of both primary tumor characteristics and type of neck dissection.

PMID- 22162248
TI  - Cloning and heterologous expression of three type II PKS gene clusters from
      Streptomyces bottropensis.
AB  - Mensacarcin is a potent cytotoxic agent isolated from Streptomyces bottropensis.
      It possesses a high content of oxygen atoms and two epoxide groups, and shows
      cytostatic and cytotoxic activity comparable to that of doxorubicin, a widely
      used drug for antitumor therapy. Another natural compound, rishirilide A, was
      also isolated from the fermentation broth of S. bottropensis. Screening a cosmid
      library of S. bottropensis with minimal PKS-gene-specific primers revealed the
      presence of three different type II polyketide synthase (PKS) gene clusters in
      this strain: the msn cluster (mensacarcin biosynthesis), the rsl cluster
      (rishirilide biosynthesis), and the mec cluster (putative spore pigment
      biosynthesis). Interestingly, luciferase-like oxygenases, which are very rare in
      Streptomyces species, are enriched in both the msn cluster and the rsl cluster.
      Three cosmids, cos2 (containing the major part of the msn cluster), cos3
      (harboring the mec cluster), and cos4 (spanning probably the whole rsl cluster)
      were introduced into the general heterologous host Streptomyces albus by
      intergeneric conjugation. Expression of cos2 and cos4 in S. albus led to the
      production of didesmethylmensacarcin (DDMM, a precursor of mensacarcin) and the
      production of rishirilide A and B (a precursor of rishirilide A), respectively.
      However, no product was detected from the expression of cos3. In addition, based
      on the results of isotope-feeding experiments in S. bottropensis, a putative
      biosynthesis pathway for mensacarcin is proposed.

PMID- 22162249
TI  - Adipose stem cells controlled by surface chemistry.
AB  - This study investigated how human adipose stem cells (hASCs) could be influenced
      by surface chemistry. Self-assembled monolayers of alkanethiolates on gold were
      introduced as a surface chemistry model to provide a range of functional groups
      such as OH, COOH, NH2, Phenyl, SH, Br, and CH3 on surfaces. Initially,
      morphological changes of hASCs in response to different surface chemistries were
      observed with focal adhesion. Cell growth behaviour evaluated by Cell Counting
      Kit-8 (CCK8) assay (Dojindo Molecular Technologies Inc., Shanghai, China) and
      cytoskeletal F-actin Biochem KitTM (Denver, CO, USA) staining revealed a
      descending order of growth rate on the following surfaces: NH2  > SH > COOH >
      Phenyl > Br > OH > CH3. The mRNA expressions of lineage specific markers
      including alkaline phosphatase (ALP), osteocalcin (OCN), type II collagen,
      aggrecan, peroxisome proliferator-activated receptor gamma (PPARgamma), and fatty
      acid binding protein-2 (aP2), were determined using real-time reversed
      transcriptase-polymerase chain reaction (RT-PCR). Results revealed that NH2
      favoured hASC differentiation toward osteogenic, while phenyl and SH promoted
      chondrogenic differentiation of hASCs with a high level up-regulation of type II
      collagen and aggrecan. hASCs on Br increased in PPARgamma and aP2 expression,
      indicating adipogenic differentiation. These results highlight the vital role of
      surface chemistry on the modulation of hASC differentiation and suggests chemical
      methods for designing biomaterials for stem cell-based tissue regeneration.

PMID- 22162250
TI  - Left-ventricular outflow tract ventricular-tachycardia event following CoreValve
      transcatheter aortic-valve implantation.
AB  - We describe a patient with severe aortic stenosis who underwent CoreValve
      (Medtronic) implantation and presented several days later with a tachyarrhythmic
      episode. The electrocardiographic features of the arrhythmia were compatible with
      left-ventricular outflow tract ventricular-tachycardia. The life-threatening
      event was not associated with ischemia or an electrolyte disorder and was not
      drug-induced. A probable cause was the irritation of the myocardium by the
      prosthetic valve. Clinicians should be aware that the presence of anatomical
      parameters that increases the risk for myocardial injury and the need for
      pacemaker implantation might indicate an increased risk of a tachyarrhythmic
      episode.

PMID- 22162251
TI  - Growth and endothelial differentiation of adipose stem cells on polycaprolactone.
AB  - Adipose tissue is a readily available source of multipotent adult stem cells for
      use in tissue engineering/regenerative medicine. Various growth factors have been
      used to stimulate acquisition of endothelial characteristics by adipose-derived
      stem cells (ADSC). Herein, we study the growth and endothelial differentiation
      potential of ADSC seeded onto a porous polycaprolactone (PCL) scaffold. The
      objective of this study is to demonstrate that PCL is a good material to be used
      as a scaffold to support reconstruction of new endothelial tissue using adipose
      stem cells. We found that undifferentiated ADSC adhere and grow on PCL. We show
      that, after culture in endothelial differentiation medium, ADSC were positive to
      LDL uptake and expressed molecular markers characteristic of endothelial cells
      (CD31; eNOS and vWF). In addition, our study defines the time required for the
      differentiation of ADSC directly onto PCL. This study suggests that PCL can be
      used as a scaffold to generate endothelial tissue in vitro. PLC has excellent
      mechanical properties and a slow degradation rate. Moreover, based on our
      results, we propose that PCL could be used to graft scaffolds coated with
      endothelial cells derived from ADSC stem cells. Endothelial cells-coated PCL
      could find several applications to replace damaged area of the body; for example,
      a possible use could be the generation of vascular grafts.

PMID- 22162252
TI  - In vitro three-dimensional (3D) models in cancer research: an update.
AB  - Tissues are three-dimensional (3D) entities as is the tumor that arises within
      them. Though disaggregated cancerous tissues have produced numerous cell lines
      for basic and applied research, it is generally agreed that these lines are poor
      models of in vivo phenomena. In this review we focus on in vitro 3D models used
      in cancer research, particularly their contribution to molecular studies of the
      early stages of metastasis, angiogenesis, the tumor microenvironment, and cancer
      stem cells. We present a summary of the various formats used in the field of
      tissue bioengineering as they apply to mechanistic modeling of cancer stages or
      processes. In addition we list studies that model specific types of malignancies,
      highlight drastic differences in results between 3D in vitro models and classical
      monolayer culturing techniques, and establish the need for standardization of 3D
      models for meaningful preclinical and therapeutic testing.

PMID- 22162253
TI  - New organic dye based on a 3,6-disubstituted carbazole donor for efficient dye
      sensitized solar cells.
AB  - We have synthesized and characterized four organic dyes (H1-H4) based on a 3,6
      disubstituted carbazole donor as sensitizers in dye-sensitized solar cells. These
      dyes have high molar extinction coefficients and energy levels suitable for
      electron transfer from an electrolyte to nanocrystalline TiO(2) particles. Under
      standard air mass 1.5 global (AM 1.5 G) solar irradiation, a device using dye H4
      exhibits a short-circuit current density (J(sc)) of 13.7 mA cm(-2), an open
      circuit voltage (V(oc)) of 0.68 V, a fill factor (FF) of 0.70, and a calculated
      efficiency of 6.52%. This performance is comparable to that of a reference cell
      based on N719 (7.30%) under the same conditions. After 1000 hours of visible
      light soaking at 60  degrees C, the overall efficiency remained at 95% of the
      initial value.

PMID- 22162254
TI  - A practical sulfenylation of 2,5-diketopiperazines.

PMID- 22162256
TI  - P-stereogenic trifluoromethyl derivatives of Josiphos: synthesis, coordination
      properties, and applications in asymmetric catalysis.
AB  - Intermolecular nucleophilic substitution of a CF(3) group of
      bis(trifluoromethyl)phosphanes by a lithiated Ugi's amine (4) affords both
      diastereoisomers of the corresponding P-stereogenic trifluoromethylphosphanes 6
      and 7. Separation of the isomers by column chromatography on silica gel followed
      by substitution of the dimethylamino group with phosphanes or pyrazoles yields
      the bidentate P^P (9 and 10) or P^N ligands (12 and 13) without epimerization at
      the stereogenic phosphorus center. The coordination properties of these bidentate
      ligands were investigated on the basis of crystal structures of the corresponding
      palladium and rhodium complexes. IR spectroscopic measurements of rhodium
      carbonyl complexes 16-23 indicated the strongly electronic-withdrawing character
      of these phosphanes. The catalytic potential of these ligands was demonstrated in
      the rhodium-catalyzed hydrogenation of olefins as well as in the palladium
      catalyzed allylic alkylation reaction, where high activities and
      enantioselectivities were observed.

PMID- 22162257
TI  - Design of molecular catalysts for achievement of high turnover number in
      homogeneous hydrogenation.
AB  - Development of highly active catalysts has been an important research area in
      synthetic chemistry, especially from a practical point of view. Herein, we focus
      on the homogeneous catalytic hydrogenation using well-defined molecular catalysts
      and discuss recent advances in the field with regard to the turnover number for
      these catalysts.

PMID- 22162255
TI  - Consensus treatment plans for induction therapy of newly diagnosed proliferative
      lupus nephritis in juvenile systemic lupus erythematosus.
AB  - OBJECTIVE: To formulate consensus treatment plans (CTPs) for induction therapy of
      newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus
      erythematosus (SLE). METHODS: A structured consensus formation process was
      employed by the members of the Childhood Arthritis and Rheumatology Research
      Alliance after considering the existing medical evidence and current treatment
      approaches. RESULTS: After an initial Delphi survey (response rate = 70%), a 2
      day consensus conference, and 2 followup Delphi surveys (response rates = 63
      79%), consensus was achieved for a limited set of CTPs addressing the induction
      therapy of proliferative LN. These CTPs were developed for prototypical patients
      defined by eligibility characteristics, and included immunosuppressive therapy
      with either mycophenolic acid orally twice per day, or intravenous
      cyclophosphamide once per month at standardized dosages for 6 months.
      Additionally, the CTPs describe 3 options for standardized use of
      glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a
      primarily intravenous regimen. There was consensus on measures of effectiveness
      and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology
      providers treating children with LN, and up to 300 children per year in North
      America are expected to be candidates for the treatment with the CTPs.
      CONCLUSION: CTPs for induction therapy of proliferative LN in juvenile SLE based
      on the available scientific evidence and pediatric rheumatology group experience
      have been developed. Consistent use of the CTPs may improve the prognosis of
      proliferative LN, and support the conduct of comparative effectiveness studies
      aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE.

PMID- 22162258
TI  - Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis
      patients: a placebo controlled study.
AB  - The constituents of Nigella sativa modulate the immune system. The aim of the
      present work was to study the effectiveness of Nigella sativa oil in RA patients.
      Data from 40 female RA patients diagnosed according to the 2010 ACR/EULAR were
      analysed and discussed. The patients took two placebo (starch filled) capsules
      daily for 1 month. This was followed by a month of Nigella sativa oil capsules
      500 mg twice/day. The disease activity score (DAS-28) significantly decreased
      after receiving the Nigella sativa capsules (4.55 +/- 0.82) compared with before
      and after placebo (4.98 +/- 0.79 and 4.99 +/- 0.72, respectively) (p = 0.017).
      Similarly, the number of swollen joints and the duration of morning stiffness
      improved. A marked improvement in the disease activity was shown by both the
      ACR20 and EULAR response criteria in 42.5% and 30% of the patients, respectively,
      after intake of Nigella. Supplementation with Nigella sativa during DMARD therapy
      in RA may be considered an affordable potential adjuvant biological therapy.

PMID- 22162259
TI  - A microporous metal-organic framework for highly selective separation of
      acetylene, ethylene, and ethane from methane at room temperature.
AB  - A novel three-dimensional microporous metal-organic framework Zn(4)L(DMA)(4)
      (UTSA-33, H(8) L=1,2,4,5-tetra(5-isophthalic acid)benzene, DMA=N,N'
      dimethylacetamide) with small pores of about 4.8 to 6.5 A was synthesized and
      structurally characterized as a non-interpenetrated (4,8)-connected network with
      the flu topology (Schlafli symbol: (4(12)6(12)8(4))(4(6))(2)). The activated UTSA
      33a exhibits highly selective separation of acetylene, ethylene, and ethane from
      methane with the adsorption selectivities of 12 to 20 at 296 K, which has been
      established exclusively by the sorption isotherms and simulated breakthrough
      experiments, thus methane can be readily separated from their binary and even
      ternary mixtures at room temperature.

PMID- 22162260
TI  - Repressor element 1 silencing transcription factor couples loss of pluripotency
      with neural induction and neural differentiation.
AB  - Neural differentiation of embryonic stem cells (ESCs) requires coordinated
      repression of the pluripotency regulatory program and reciprocal activation of
      the neurogenic regulatory program. Upon neural induction, ESCs rapidly repress
      expression of pluripotency genes followed by staged activation of neural
      progenitor and differentiated neuronal and glial genes. The transcriptional
      factors that underlie maintenance of pluripotency are partially characterized
      whereas those underlying neural induction are much less explored, and the factors
      that coordinate these two developmental programs are completely unknown. One
      transcription factor, REST (repressor element 1 silencing transcription factor),
      has been linked with terminal differentiation of neural progenitors and more
      recently, and controversially, with control of pluripotency. Here, we show that
      in the absence of REST, coordination of pluripotency and neural induction is lost
      and there is a resultant delay in repression of pluripotency genes and a
      precocious activation of both neural progenitor and differentiated neuronal and
      glial genes. Furthermore, we show that REST is not required for production of
      radial glia-like progenitors but is required for their subsequent maintenance and
      differentiation into neurons, oligodendrocytes, and astrocytes. We propose that
      REST acts as a regulatory hub that coordinates timely repression of pluripotency
      with neural induction and neural differentiation.

PMID- 22162261
TI  - Irresolvable complex mixture of hydrocarbons in soybean oil deodorizer
      distillate.
AB  - Aliphatic hydrocarbons (HCs) can be used as a fingerprint of a given seed oil.
      Only by characterization of aliphatic HCs could contamination by mineral oil in
      that seed oil be confirmed. During the isolation of squalene from soybean oil
      deodorizer distillate, a significant amount of unknown HCs, ca. 44 wt%, was
      obtained. These seemingly-easy-to-identify HCs turned out to be much more
      difficult to elucidate due to the presence of an irresolvable complex mixture
      (ICM). The objective of this study was to purify and identify the unknown ICM of
      aliphatic HCs from soybean oil deodorizer distillate. Purification of the ICM was
      successfully achieved by using modified Soxhlet extraction, followed by modified
      preparative column chromatography, and finally by classical preparative column
      chromatography. FT-IR, TLC, elemental analysis, GC/FID, NMR and GC-MS analyses
      were then performed on the purified HCs. The GC chromatogram detected the
      presence of ICM peaks comprising two major peaks and a number of minor peaks.
      Validation methods such as IR and NMR justified that the unknowns are saturated
      HCs. This work succeeded in tentatively identifying the two major peaks in the
      ICM as cycloalkane derivatives. 

PMID- 22162262
TI  - The mechanism of cleavage and isomerisation of RNA promoted by an efficient
      dinuclear Zn2+ complex.
AB  - The cleavage and isomerisation of uridine 3'-alkylphosphates was studied in the
      presence of a dinuclear Zn(2+) complex, 3. The rate acceleration of the cleavage
      by 1 mM 3 is approximately 10(6)-fold under neutral conditions. Most remarkably,
      the complex also promotes the isomerisation of phosphodiester bonds, although the
      rate-enhancement is more modest: under neutral conditions complex 3 (1 mM)
      catalyses isomerisation by about 500-fold. The observation of this reaction shows
      that the reactions of these substrates catalysed by 3 proceed through a stepwise
      mechanism involving an intermediate phosphorane. A beta(lg) value of -0.92 was
      determined for the 3-promoted cleavage reaction, and modest kinetic solvent
      deuterium isotope effects ranging from 1.5 to 2.8 were observed. Isomerisation
      was less sensitive to the nature of the esterifying group, with a beta value of 
      0.5, and the kinetic solvent deuterium isotope effects were less than 1.5. Most
      of these characteristics of the 3-promoted cleavage are very similar to those for
      the cleavage of nucleoside 3'-phosphotriesters. These data are explained by a
      mechanism in which the complex primarily acts as an electrophilic catalyst
      neutralising the charge on the phosphate and stabilising an intermediate
      phosphorane, with general acid catalysis promoting the cleavage reaction. In
      contrast to the behaviour of triesters, isomerisation is significantly slower
      than cleavage; this suggests that the changes in geometry that occur during
      isomerisation lead to a much less stable complex between 3 and the phosphorane
      intermediate.

PMID- 22162263
TI  - A DNA-based light-harvesting antenna.

PMID- 22162264
TI  - Novel use of a pericardium-covered stent graft to treat bulky coronary artery
      thrombus.
AB  - OBJECTIVES: We studied the acute safety and feasibility of a pericardium-covered
      stent (PCS) in the obliteration of massive coronary thrombus. BACKGROUND:
      Thrombus is frequently encountered in the setting of acute myocardial infarction,
      and conventional pharmacological and aspiration approaches are not always
      successful in dispersing or removing it, especially when it is very substantial.
      METHODS: We treated nine patients (10 lesions) in the setting of an acute
      coronary syndrome characterized by the presence of substantial (TIMI grade 3-4)
      thrombus in a large caliber native coronary artery, persisting after conventional
      treatment, with percutaneous implantation of an equine PCS graft. Nine of 10
      lesions were in large right coronary arteries. RESULTS: Deployment was successful
      in nine of 10 lesions. In all nine cases, the filling defect was immediately
      eliminated and there was restoration or maintenance of TIMI grade 3 blood flow.
      There was one in-hospital stent thrombosis in a 56-year-old male, who had only
      received aspirin due to a coexistent stroke. This patient underwent successful
      repeat percutaneous intervention but died later of complications of the stroke.
      There were no 30-day events, and medium-term follow-up continues. CONCLUSIONS: A
      PCS graft is a potentially useful device to treat massive thrombus burden in the
      setting of acute coronary syndrome. A larger study is warranted.

PMID- 22162265
TI  - Functional role of scaffold geometries as a template for physiological ECM
      formation: evaluation of collagen 3D assembly.
AB  - Bone tissue regeneration involves different healing stages and the resulting
      final hard tissue is formed from natural templates such as fibrous collagen, soft
      and hard callus and capillary bed. This work aims to evaluate the efficiency of
      different scaffold geometries with a novel approach: exploring the relationships
      among scaffold morphologies, cell activity and collagen 3D organization, which
      serves as a natural template for subsequent mineralization. Among the possible
      systems to fabricate scaffolds, solvent casting with particulate leaching and
      microfabrication were used to produce random vs ordered structures from poly(D,L
      lactic acid). In vitro biological testing was carried out by culturing a human
      osteosarcoma-derived osteoblast cell line (MG63) and measuring material
      cytotoxicity, cell proliferation and migration. Assemblage of collagen fibres was
      evaluated. A preliminary study of collagen distribution over the two different
      matrices was performed by confocal laser microscopy after direct red 80 staining.
      Both of the scaffolds were seen to be a good substrate for cell attachment,
      growth and proliferation. However, it seems that random, rather than regular,
      well-ordered porosity induces a more proper collagen fibre distribution and
      organization, similar to the natural one formed in the early stages of bone
      repair.

PMID- 22162266
TI  - Molecular and immunological characterization of Mus a 5 allergen from banana
      fruit.
AB  - SCOPE: Banana fruit has become an important cause of fruit allergy in the recent
      years. Among the five registered IUIS allergens, Mus a 1 and Mus a 2 have been
      characterized in detail. In this study, molecular characterization and evaluation
      of the allergenic properties of beta-1,3-glucanase from banana (Musa acuminata),
      denoted as Mus a 5, were performed. METHODS AND RESULTS: The gene of Mus a 5 was
      cloned and sequenced. The obtained cDNA revealed a novel Mus a 5 isoform with an
      open reading frame encoding a protein of 340 amino acids comprising a putative
      signal peptide of 28 amino acid residues. By MALDI-TOF analysis Mus a 5 isolated
      from banana fruit revealed a molecular mass of 33451+/-67 Da. Two Mus a 5
      isoforms (pI 7.7 and 8.0) were detected by 2D immunoblot with an identical N
      terminal sequence. By mass fingerprint, 76 and 83% of the primary structure was
      confirmed for the two mature Mus a 5 isoforms, respectively. IgE reactivity to
      Mus a 5 was found in 74% of patients sensitized to banana fruit. Upregulation of
      basophil activation markers CD63 and CD203c was achieved with Mus a 5 in a
      concentration-dependent manner. CONCLUSION: Mus a 5 is a functional allergen and
      a candidate for the component-resolved allergy diagnosis of banana allergy.

PMID- 22162267
TI  - UM-SCC-104: a new human papillomavirus-16-positive cancer stem cell-containing
      head and neck squamous cell carcinoma cell line.
AB  - BACKGROUND: Few human papillomavirus (HPV)(+) head and neck squamous cell
      carcinoma (HNSCC) cell lines exist. We established University of Michigan
      squamous cell carcinoma-104 (UM-SCC-104), a new HPV(+) HNSCC cell line from a
      recurrent oral cavity tumor, and characterized it for the presence of cancer stem
      cells (CSCs). METHODS: Tumor cells were tested for biomarker expression by
      immunohistology, and the presence of HPV was assessed by several methods.
      RESULTS: UM-SCC-104 has a unique genotype, contains HPV-16, and expresses E6/E7.
      Inoculation of aldehyde dehydrogenase (ALDH)(+) and ALDH(-) cells in an
      immunocompromised mouse resulted in tumor growth from the ALDH(+) cells after 6
      weeks that recapitulated the histology of the primary, whereas ALDH(-) cells did
      not produce tumors. CONCLUSION: UM-SCC-104, a new HPV-16, CSC-containing HNSCC
      cell line will aid in studying recurrent HPV(+) tumors. The aggressive nature of
      this tumor is consistent with high uniform expression of epidermal growth factor
      receptor (EGFR) and a functionally significant proportion of ALDH(+) CSCs.

PMID- 22162268
TI  - Synthesis and evaluation of a fluorescent non-peptidic cholecystokinin-B/gastrin
      receptor specific antagonist for cancer cell imaging.
AB  - Fluorescent labeling has enabled a better understanding of the relationships
      between receptor location, function, and life cycle. Each of these perspectives
      contributes new insights into drug action, particularly for G protein-coupled
      receptors (GPCRs). The aim of this study was to develop a fluorescein derivative,
      FLUO-QUIN-a novel antagonist of the cholecystokinin-B/gastrin receptor. A
      radioligand-binding experiment revealed an IC(50)  of 4.79 nm, and the antagonist
      inhibited gastric acid secretion in an isolated lumen-perfused mouse stomach
      assay (up to 51 % at 100 nm). The fluorescence properties altered upon binding to
      the receptor, and the fluorophore was quenched to a greater extent when free than
      in the bound form. FLUO-QUIN specifically bound to human pancreatic carcinoma
      cells, MiaPaca-2, which are known to express the receptor, as evidenced by rapid
      clustering followed by time-dependent receptor internalization. This proves the
      stability of FLUO-QUIN and its ability to penetrate vesicular membranes and reach
      various cell targets. Hence it might be used as an agent for the detection of CCK
      B-receptor-positive tumors by fluorescence imaging.

PMID- 22162269
TI  - In vitro wear performance of standard, crosslinked, and vitamin-E-blended UHMWPE.
AB  - Crosslinked vitamin-E-stabilized polyethylene acetabular cups were compared with
      both commercially available conventional and custom-crosslinked polyethylene
      acetabular cups in terms of wear behavior, in a hip joint simulator for five
      millions cycles, using bovine calf serum as lubricant. We correlated the wear
      experiments results with the chemical characterization of the investigated
      materials: Fourier transformed infrared (FTIR) spectroscopic analyses,
      differential scanning calorimetry, and crosslink density measurements were used
      to assess the chemical characteristics of the pristine materials. In addition,
      further FTIR analyses and cyclohexane extraction were carried out after the
      simulator experiments. Lipids absorption was observed in all tested specimens and
      it has been shown to strongly affect the results of the wear test. Corrected
      gravimetric wear measurements showed that vitamin-E blended, crosslinked
      polyethylene wore more than the traditional crosslinked polyethylene but
      exhibited a much lower wear than conventional ultrahigh-molecular weight
      polyethylene. The chemical analyses showed that the addition of vitamin E reduced
      the crosslinking efficiency. Given the correlation between crosslink density and
      wear resistance, this gave an explanation for the observed wear performances.

PMID- 22162270
TI  - Persilastaffanes: design, synthesis, structure, and conjugation between silicon
      cages.

PMID- 22162272
TI  - Fritz Haber: flawed greatness of person and country.

PMID- 22162273
TI  - Magnetotransport properties and kondo effect observed in a ferromagnetic single
      crystalline Fe(1-x)Co(x)Si nanowire.
AB  - We report unconventional magnetotransport properties of an individual Fe(1
      x)Co(x)Si nanowire. We have studied the dependence of the resistivity on the
      angle between the directions of the magnetization and electrical current below
      the Curie temperature (T(C)). The observed anisotropic magnetoresistance (MR)
      ratio is negative, thereby indicating that the conduction electrons in a minority
      spin band of the Fe(1-x)Co(x)Si nanowire dominantly contribute to the transport.
      Unlike typical ferromagnets, positive MR is observed in the overall temperature
      range. MR curves are linear below T(C) and show a quadratic form above T(C),
      which can be explained by the change of density of states that arises as the band
      structures of the Fe(1-x)Co(x)Si nanowire shift under a magnetic field. The
      temperature dependence of the resistivity curve is sufficiently explained by the
      Kondo effect. The Kondo temperature of the Fe(1-x)Co(x)Si nanowire is lower than
      that of the bulk state due to suppression of the Kondo effect. The high single
      crystallinity of Fe(1-x)Co(x)Si nanowires allowed us to observe and interpret
      quite subtle variations in the prominent intrinsic transport properties.

PMID- 22162274
TI  - Analysis of NAD 2D-NMR spectra of saturated fatty acids in polypeptide aligning
      media by experimental and modeling approaches.
AB  - The overall and detailed elucidation (including the stereochemical aspects) of
      enzymatic mechanisms requires the access to all reliable information related to
      the natural isotopic fractionation of both precursors and products. Natural
      abundance deuterium (NAD) 2D-NMR experiments in polypeptide liquid-crystalline
      solutions are a new, suitable tool for analyzing site-specific deuterium isotopic
      distribution profiles. Here this method is utilized for analyzing saturated C14
      to C18 fatty acid methyl esters (FAMEs), which are challenging because of the
      crowding of signals in a narrow spectral region. Experiments in achiral and
      chiral oriented solutions were performed. The spectral analysis is supplemented
      by the theoretical prediction of quadrupolar splittings as a function of the
      geometry and flexibility of FAMEs, based on a novel computational methodology.
      This allows us to confirm the spectral assignments, while providing insights into
      the mechanism of solute ordering in liquid-crystalline polypeptide solutions.
      This is found to be dominated by steric repulsions between FAMEs and
      polypeptides.

PMID- 22162275
TI  - Effects of ortho-dihydroxyisoflavone derivatives from Korean fermented soybean
      paste on melanogenesis in B16 melanoma cells and human skin equivalents.
AB  - In this study we investigated the inhibitory effects and possible mechanisms of
      action of 8'-hydroxydaidzein and 3'-hydroxydaidzein, two ortho
      dihydroxyisoflavone derivatives from Korean fermented soybean paste, on
      melanogenesis in B16 murine melanoma cells. The two hydroxydaidzeins reduced
      melanin synthesis comparably to treatment with kojic acid, a proven whitening
      agent, in B16 melanoma cells. Furthermore, when in vitro human skin equivalents
      were treated with the hydroxydaidzeins, the levels of melanogenesis were
      significantly reduced relative to a kojic acid control. The RT-PCR results
      demonstrated that depigmentation was due to transcriptional repression of several
      melanogenesis genes, including microphthalmia-associated transcription factor
      (MITF), by the hydroxydaidzeins. The immunoblotting results confirmed that
      diminution of MITF expression subsequently decreased expression of tyrosinase,
      and tyrosinase-related proteins 1 and 2. Cumulatively, these results suggest that
      hydroxydaidzeins would be potent attenuators of melanin synthesis as well as
      effective inhibitors of hyperpigmentation in human skin.

PMID- 22162276
TI  - Modification of pax6 and olig2 expression in adult hippocampal neurogenesis
      selectively induces stem cell fate and alters both neuronal and glial
      populations.
AB  - The generation of new neurons in the mammalian hippocampus continues throughout
      life, and lineage progression is regulated by transcription factors, local cues,
      and environmental influences. The ability to direct stem/progenitor cell fate in
      situ may have therapeutic potential. Using an in vivo retroviral delivery and
      lineage tracing approach, we compare the lineage-instruction factors, Pax6 and
      Olig2, and demonstrate that both participate in regulation of adult hippocampal
      neurogenesis in adult rats. We show that overexpression of the proneuronal factor
      Pax6 pushes neuronal precursor cells to early maturation and increases the
      frequency of neuronal phenotypes. However, Pax6 overexpression results in no net
      increase in neurogenesis at 3 weeks. Blocking of Olig2 function reduces and slows
      neuronal commitment and differentiation and decreases net neurogenesis. Altering
      expression of both factors also changes gliogenesis. Our results establish that
      Pax6 decreases the number of Neuron-Glia 2 progenitor cells and prevents
      oligodendrocytic lineage commitment, while repression of Olig2 results in an
      expanded astrocytic lineage. We conclude that selectively modifying
      transcriptional cues within hippocampal progenitor cells is sufficient to induce
      a cell fate switch, thus altering the neurogenesis-gliogenesis ratio. In
      addition, our data show the competence of multiple progenitor lineages to respond
      divergently to the same signal. Therefore, directing instructive cues to select
      phenotype and developmental stage could be critical to achieve precise outcomes
      in cell genesis. Further understanding the regulation of lineage progression in
      all progenitor populations within the target region will be important for
      developing therapeutic strategies to direct cell fate for brain repair.

PMID- 22162278
TI  - Characterization of hexacationic imidazolium ionic liquids as effective and
      highly stable gas chromatography stationary phases.
AB  - Polycationic ionic liquids (ILs) are an attractive class of ILs with great
      potential applicability as gas chromatography stationary phases. A family of
      hexacationic imidazolium ILs derived from the cycloalkanol family was chemically
      first prepared in a straightforward manner and then applied for analytical
      separation purposes. Four tuneable engineering vectors, namely cation ring size
      structure, anion nature, spatial disposition of cycloalkanol substituents and O
      substitution, were considered as experimental parameters for the design of the
      desired ionic liquids. A total number of five new phases based on a common
      benzene core respectively exhibited column efficiencies around to 2500 plates/m,
      broad operating temperature ranges and also, even more importantly, good thermal
      stabilities (bleeding temperature between 260 and 365 degrees C), finding
      variations in the selectivity and analytes elution orders depending on the IL
      structures. Their solvation characteristics were evaluated using the Abraham
      solvation parameter model, establishing clear correlations between their cation
      structure and retention capability with respect to certain analytes. The study of
      relationships between the ILs structure and solvation parameters gives us an idea
      of the IL stationary phase to be used for specific separations. 

PMID- 22162277
TI  - The union of anti-CD34 antibody can improve the performance of drug-eluting
      stents.
AB  - OBJECTIVES: The authors investigate whether the combination of anti-CD34 antibody
      with DES is win-win cooperation. BACKGROUND: DES may reduce the risk of
      restenosis compared to bare-metal stents (BMS), but they were found to inhibit
      the healing process of intima. METHODS: Fifteen BMS, 17 DES, and 16 combined anti
      CD34 antibody and DES were randomly implanted in the coronary arteries of 22
      minipigs. Ten minipigs were followed up to 2 weeks. The stenting coronary
      segments were examined by histological examination and scanning electron
      microscopy after in vivo coronary angiography and intracoronary optical coherence
      tomography (OCT) examinations. The other 12 minipigs were followed up to 3
      months. Coronary angiography and intracoronary OCT examination were performed in
      vivo and histological examination was performed on the stenting coronary
      segments. RESULTS: After 2 weeks, the neointimal covering level of the DES was
      lower than that in BMS, but the covering level of the combined stents was even
      better than the BMS. After 3 months, neointimal hyperplasia was significant in
      the BMS, but not in the other two types of stents. The in-stent late lumen loss
      of the combined stents even showed a decreasing tendency when compared with the
      DES. CONCLUSION: The combination of anti-CD34 antibody and DES can not only well
      offset the short-term inhibitory effect on re-endothelialization but also
      slightly enhance the long-term antiproliferative effect.

PMID- 22162279
TI  - Custom foot orthoses for rheumatoid arthritis: A systematic review.
AB  - OBJECTIVE: To identify and critically appraise the evidence for the effectiveness
      of custom orthoses for the foot and ankle in rheumatoid arthritis. METHODS:
      Studies were identified in appropriate electronic databases (from 1950 to March
      2011). The search term "rheumatoid arthritis" with "foot" and "ankle" and related
      terms were used in conjunction with "orthoses" and synonyms. Included studies
      were quantitative longitudinal studies and included randomized controlled trials
      (RCTs), case-control trials, cohort studies, and case series studies. All outcome
      measures were investigated. Quality assessment was conducted using the Cochrane
      Collaboration criteria with additional criteria for sample population
      representativeness, quality of statistical analysis, and compliant intervention
      use and presence of cointerventions. Meta-analyses were conducted for outcome
      domains with multiple RCTs. Qualitative data synthesis was conducted for the
      remaining outcome domains. Levels of evidence were then assigned to each outcome
      measure. RESULTS: The inclusion criteria were met by 17 studies. Two studies had
      high quality for internal validity and 3 studies had high quality for external
      validity. No study had high quality for both internal and external validity. Six
      outcome domains were identified. There was weak evidence for custom orthoses
      reducing pain and forefoot plantar pressures. Evidence was inconclusive for foot
      function, walking speed, gait parameters, and reducing hallux abductovalgus angle
      progression. CONCLUSION: Custom orthoses may be beneficial in reducing pain and
      elevated forefoot plantar pressures in the rheumatoid foot and ankle. However,
      more definitive research is needed in this area.

PMID- 22162280
TI  - Respirable rifampicin-based microspheres containing isoniazid for tuberculosis
      treatment.
AB  - The purpose of this investigation was to develop small microspheres for
      delivering antimycobacterial drugs to infected host macrophages. Rifampicin-based
      microparticles were prepared. The drug was covalently linked to acrylic moieties
      to obtain a polymerizable derivative for the preparation of materials useful as
      drug delivery systems that then were loaded with isoniazid acting in synergy with
      rifampicin. Their antitubercular activity was determined in vitro. Fourier
      transform infrared spectroscopy confirmed hydrogel structure. Morphological
      analysis showed microparticles with spherical shape and homogeneous surface. In
      vitro release studies were performed in media simulating physiologic pH (7.4) and
      endosomal of alveolar macrophages pH (5.2). A similar amount of isoniazid was
      delivered within the first 6 h at both pHs, while a smaller amount of the drug
      was delivered at pH 7.4 in the last phase of the study. In vitro antitubercular
      activity showed a behavior comparable to that of rifampicin and isoniazid free.
      Bioactive swelling matrices, showing a high swelling degree into a medium miming
      intra alveolar environment, were obtained. They could be applied for their
      antitubercular activity.

PMID- 22162281
TI  - Gold nanoparticles incarcerated in nanoporous syndiotactic polystyrene matrices
      as new and efficient catalysts for alcohol oxidations.
AB  - The controlled synthesis of gold nanoparticles (AuNPs), incarcerated in a
      semicrystalline nanoporous polymer matrix that consisted of a syndiotactic
      polystyrene-co-cis-1,4-polybutadiene multi-block copolymer is described. This
      catalyst was successfully tested in the oxidation of primary and secondary
      alcohols, in which we used dioxygen as the oxidant under mild conditions.
      Accordingly, (+/-)-1-phenylethanol was oxidised to acetophenone in high yields
      (96%) in 1 h, at 35  degrees C, whereas benzyl alcohol was quantitatively
      oxidised to benzaldehyde with a selectivity of 96% in 6 h. The specific rate
      constants calculated from the corresponding kinetic plots were among the highest
      found for polymer-incarcerated AuNPs. Similar values in terms of reactivity and
      selectivity were found in the oxidation of primary alcohols, such as cinnamyl
      alcohol and 2-thiophenemethanol, and secondary alcohols, such as indanol and
      alpha-tetralol. The remarkable catalytic properties of this system were
      attributed to the formation, under these reaction conditions, of the nanoporous
      epsilon crystalline form of syndiotactic polystyrene, which ensures facile and
      selective accessibility for the substrates to the gold catalyst incarcerated in
      the polymer matrix. Moreover, the polymeric crystalline domains produced
      reversible physical cross-links that resulted in reduced gold leaching and also
      allowed the recovery and reuse of the catalyst. A comparison of catalytic
      performance between AuNPs and annealed AuNPs suggested that multiple twinned
      defective nanoparticles of about 9 nm in diameter constituted the active catalyst
      in these oxidation reactions.

PMID- 22162282
TI  - Enzymatic recognition of 2'-modified ribonucleoside 5'-triphosphates: towards the
      evolution of versatile aptamers.
AB  - The quest for effective, selective and nontoxic nucleic-acid-based drugs has led
      to designing modifications of naturally occurring nucleosides. A number of
      modified nucleic acids have been made in the past decades in the hope that they
      would prove useful in target-validation studies and therapeutic applications
      involving antisense, RNAi, aptamer, and ribozyme-based technologies. Since their
      invention in the early 1990s, aptamers have emerged as a very promising class of
      therapeutics, with one drug entering the market for the treatment of age-related
      macular degeneration. To combat the limitations of aptamers containing naturally
      occurring nucleotides, chemically modified nucleotides have to be used. In order
      to apply modified nucleotides in aptamer drug development, their enzyme
      recognition capabilities must be understood. For this purpose, several modified
      nucleoside 5'-triphosphates were synthesized and investigated as substrates for
      various enzymes. Herein, we review studies on the enzyme-recognition of various
      2'-sugar-modified NTPs that were carried out with a view to their effective
      utilization in SELEX processes to generate versatile aptamers.

PMID- 22162283
TI  - Catalytically propelled micro-/nanomotors: how fast can they move?
AB  - Synthetic micro-/nanomotors represent one of the most exciting challenges facing
      nanotechnology and hold considerable promise for diverse future applications.
      This review discusses different strategies to improve the speed of the catalytic
      nanomotors, summarizing and comparing the maximum absolute and relative speeds
      obtained with different catalytically propelled micro-/nanomotors. Remarkably
      ultrafast nanowires and microtube engines, with speeds of 60 and 375 body lengths
      s(-1), respectively, have been developed recently. Achieving such amazingly high
      speed and power has been accomplished through rational optimization of key
      factors governing the propulsion behavior, including composition of the motor and
      fuel, the motor morphology and various external stimuli. We hope that our
      discussion will serve as a guide to the rational design of even faster and more
      powerful catalytically propelled fuel-efficient micro-/nanomotors, with speed
      limits that are limited only by our imagination.

PMID- 22162284
TI  - Etiology of potentially primordial biomolecular structures: from vitamin B12 to
      the nucleic acids and an inquiry into the chemistry of life's origin: a
      retrospective.
AB  - "We'll never be able to know" is a truism that leads to resignation with respect
      to any experimental effort to search for the chemistry of life's origin. But such
      resignation runs radically counter to the challenge imposed upon chemistry as a
      natural science. Notwithstanding the prognosis according to which the shortest
      path to understanding the metamorphosis of the chemical into the biological is by
      way of experimental modeling of "artificial chemical life", the scientific search
      for the route nature adopted in creating the life we know will arguably never
      truly end. It is, after all, part of the search for our own origin.

PMID- 22162285
TI  - Photoreversible patterning of biomolecules within click-based hydrogels.

PMID- 22162286
TI  - New insights into epithelial differentiation of human adipose-derived stem cells.
AB  - Although many studies using stem cells as therapeutic agents after renal failure
      have been published in recent years, our knowledge of the factors involved and
      the cellular mechanisms underlying their beneficial effect on organ regeneration
      is incomplete. A growing insight into these interactions would help to utilize
      the biological potential of stem cells for therapeutic approaches. It is here
      hypothesized that soluble factors released by tubular epithelial cells (TECs)
      induce epithelial differentiation in adipose-derived adult mesenchymal stem cells
      (ASCs). ASCs were therefore cultured in conditioned medium (CM) derived from TECs
      and the changes in expression genes towards an epithelial pattern were determined
      by microarray and qPCR analyses. The changes in gene expression were evaluated
      using Affymetrix HG-U133 Plus 2.0 arrays. Microarray-based screening revealed 117
      genes differentially expressed in a significant manner after short-time
      incubation (3 days) of ASCs with CM, and four of these were solute carriers
      (SLCs). Changes in mRNA expression of these SLCs were verified by qPCR at several
      time points, additionally with four stem cell factors and five epithelial
      markers. qPCR analyses showed that expression of three of the SLCs rose
      significantly, whereas three of the four stem cell markers analysed decreased
      during 7 days of CM incubation. Moreover, a robust expression of three
      characteristic epithelial markers (cytokeratin 18, ZO-1 and ZO-2) was observed
      after 17 days. These changes in the expression patterns strongly indicate
      differentiation towards the epithelial lineage. The capability of ASCs to
      differentiate into epithelial cells may be important in organ repair mechanisms.

PMID- 22162287
TI  - Metabolomics for measuring phytochemicals, and assessing human and animal
      responses to phytochemicals, in food science.
AB  - Metabolomics, comprehensive metabolite analysis, is finding increasing
      application as a tool to measure and enable the manipulation of the phytochemical
      content of foods, to identify the measures of dietary intake, and to understand
      human and animal responses to phytochemicals in the diet. Recent applications of
      metabolomics directed toward understanding the role of phytochemicals in food and
      nutrition are reviewed.

PMID- 22162288
TI  - ETV6 rearrangements are recurrent in myeloid malignancies and are frequently
      associated with other genetic events.
AB  - ETV6 (TEL) rearrangements are favorable in pediatric acute lymphoblastic leukemia
      but are less well characterized in myeloid malignancies. We investigated 9,550
      patients with myeloid disorders for ETV6 rearrangements by chromosome banding
      analysis and interphase fluorescence in situ hybridization. ETV6 rearrangements
      were identified in 51 of 9,550 (0.5%) patients (range, 19.2-85.3 years).
      Frequencies were in detail: acute myeloid leukemia (AML): 40 of 3,798, 1.1%;
      myelodysplastic syndromes (MDS): 6 of 3,375, 0.2%; myeloproliferative neoplasms
      (MPNs): 5 of 1,720, 0.3%; MDS/MPN: 0 of 210; and chronic myelomonocytic leukemia:
      0 of 447. Thirty-three different partner bands of ETV6 were identified, and most
      were recurrent: 3q26 (n = 10), 5q33 (n = 4), 17q11 (n = 3), 22q12 (n = 3), 5q31
      (n = 2), and 2q31 (n = 2). Additional chromosomal abnormalities were identified
      in 29 of 51 (57%) ETV6 rearranged cases. In AML, ETV6 rearrangements were
      frequently associated with NPM1 (9/39, 23%) and RUNX1 mutations (6/31, 19%). The
      FAB M0 subtype was more frequent in ETV6 rearranged de novo AML than other AML (P
      < 0.001); expression of CD7 and CD34 by immunophenotyping was higher in ETV6
      rearranged AML compared with other subgroups. Survival of 29 ETV6 rearranged de
      novo AML was compared with 818 AML from other cytogenetic subgroups. Median
      overall and event-free survival of ETV6 rearranged cases was similar to the
      intermediate-risk cohort (26.3 vs. 62.2 months and 14.0 vs. 15.4 months) defined
      according to Medical Research Council criteria. Our study confirms the variety of
      ETV6 rearrangements in AML, MDS, and MPNs often in association with other genetic
      events. Prognosis of ETV6 rearranged de novo AML seems to be intermediate, which
      should be independently confirmed.

PMID- 22162289
TI  - Major challenges ahead for Hungarian healthcare.

PMID- 22162290
TI  - More secrets of the MMR scare. Where did the specimens come from?

PMID- 22162291
TI  - Amar Dhillon replies to "Pathology reports solve 'new bowel disease' riddle".

PMID- 22162292
TI  - BMA moves to full opposition on healthcare reforms.

PMID- 22162293
TI  - Nominations open for BMJ Group awards 2012.

PMID- 22162294
TI  - Clinical grade stem cells are created by scientists in London.

PMID- 22162295
TI  - Nanoporous carbon materials for electrochemical sensing.
AB  - Nanoporous carbon materials are highly important materials for a wide array of
      applications. Here we show that nanoporous carbon can act as highly active
      materials for electrochemical sensing. We observed that nanoporous carbon
      material exhibits a faster heterogeneous electron transfer than graphite and pure
      carbon nanotubes. Nanoporous carbon exhibits a superior electrochemical
      performance for sensing of important biomarkers such as dopamine, ascorbic acid,
      uric acid, NADH, DNA bases, and forensic-related compounds such as nitroaromatic
      explosives.

PMID- 22162296
TI  - Highly selective palladium-catalyzed intramolecular chloroamination of
      unactivated alkenes by using hydrogen peroxide as an oxidant.

PMID- 22162297
TI  - CatApp: a web application for surface chemistry and heterogeneous catalysis.

PMID- 22162298
TI  - Effects of Panax notoginseng saponins on the activities of CYP1A2, CYP2C9, CYP2D6
      and CYP3A4 in rats in vivo.
AB  - The aim of this study was to assess the influence of the Panax notoginseng
      saponins (PNS) on the activities of the drug-metabolizing enzymes cytochrome P450
      (CYP450) 1A2, 2 C9, 2D6 and 3A4 in rats. The activities of CYP1A2, 2 C9, 2D6 and
      3A4 were measured using specific probe drugs. After pretreatment for 1 week with
      PNS or physiological saline (control group), probe drugs caffeine (10 mg/kg;
      CYP1A2 activity), tolbutamide (15 mg/kg; CYP2C9 activity), metoprolol (20 mg/kg;
      CYP2D6 activity) and dapsone (10 mg/kg; CYP3A4 activity) were administered to
      rats by intraperitoneal injection. The blood was then collected at different
      times for ultra performance liquid chromatography/tandem mass spectrometry (UPLC
      MS/MS) analysis. The data showed that PNS exhibited an induction effect on CYP1A2
      by decreasing caffeine C(max) (36.3%, p < 0.01) and AUC(0-infinity) (22.77%, p <
      0.05) and increasing CL/F (27.03%, p < 0.05) compared with those of the control
      group. Western blot analysis was used to detect the effect of PNS on the protein
      level of CYP1A2, and the results showed that PNS could upregulate the protein
      expression of CYP1A2. However, no significant changes in CYP2C9, 2D6 or 3A4
      activities were observed. In conclusion, the results indicate that PNS could
      induce CYP1A2, which may affect the disposition of medicines primarily dependent
      on the CYP1A2 pathway. Our work may be the basis of related herb-drug
      interactions in the clinic.

PMID- 22162299
TI  - Editorial: Our top 10 developments in stem cell biology over the last 30 years.
AB  - To celebrate 30 years of peer-reviewed publication of cutting edge stem cell
      research in Stem Cells, the first journal devoted to this promising field, we
      pause to review how far we have come in the three-decade lifetime of the Journal.
      To do this, we will present our views of the 10 most significant developments
      that have advanced stem cell biology where it is today. With the increasing rate
      of new data, it is natural that the bulk of these developments would have
      occurred in recent years, but we must not think that stem cell biology is a young
      science. The idea of a stem cell has actually been around for quite a long time
      having appeared in the scientific literature as early as 1868 with Haeckels'
      concept of a stamzelle as an uncommitted or undifferentiated cell responsible for
      producing many types of new cells to repair the body [Naturliche
      Schopfungsgeschichte, 1868; Berlin: Georg Reimer] but it took many years to
      obtain hard evidence in support of this theory. Not until the work of James Till
      and Ernest McCulloch in the 1960s did we have proof of the existence of stem
      cells and until the derivation of embryonal carcinoma cells in the 1960s-1970s
      and the first embryonic stem cell in 1981, such adult or tissue-specific stem
      cells were the only known class. The first issue of Stem Cells was published in
      1981; no small wonder that most of its papers were devoted to hematopoietic
      progenitors. More recently, induced pluripotent stem cells (iPSCs) have been
      developed, and this is proving to be a fertile area of investigation as shown by
      the volume of publications appearing not only in Stem Cells but also in other
      journals over the last 5 years. The reader will note that many of the articles in
      this special issue are concerned with iPSC; however, this reflects the current
      surge of interest in the topic rather than any deliberate attempt to ignore other
      areas of stem cell investigation.

PMID- 22162300
TI  - Growth factor release from a chemically modified elastomeric poly(1,8-octanediol
      co-citrate) thin film promotes angiogenesis in vivo.
AB  - The ultimate success of in vivo organ formation utilizing ex vivo expanded
      "starter" tissues relies heavily upon the level of vascularization provided by
      either endogenous or artificial induction of angiogenic or vasculogenic events.
      To facilitate proangiogenic outcomes and promote tissue growth, an elastomeric
      scaffold previously shown to be instrumental in the urinary bladder regenerative
      process was modified to release proangiogenic growth factors. Carboxylic acid
      groups on poly(1,8-octanediol-co-citrate) films (POCfs) were modified with
      heparan sulfate creating a heparan binding POCf (HBPOCf). Release of
      proangiogenic growth factors vascular endothelial growth factor (VEGF),
      fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 (IGF-1) from
      HBPOCfs demonstrated an approximate threefold increase over controls during a 30
      day time course in vitro. Atomic force microscopy demonstrated significant
      topological differences between films. Subcutaneous implantation of POCf alone,
      HBPOCf, POCf-VEGF, and HBPOCf-VEGF within the dorsa of nude rats yielded
      increased vascular growth in HBPOCf-VEGF constructs. Vessel quantification
      studies revealed that POCfs alone contained 41.1 +/- 4.1 vessels/mm2, while
      HBPOCf, POCf-VEGF, and HBPOCF-VEGF contained 41.7 +/- 2.6, 76.3 +/- 9.4, and
      167.72 +/- 15.3 vessels/mm2, respectively. Presence of increased vessel growth
      was demonstrated by CD31 and vWF immunostaining in HBPOCf-VEGF implanted areas.
      Data demonstrate that elastomeric POCfs can be chemically modified and possess
      the ability to promote angiogenesis in vivo.

PMID- 22162301
TI  - Touchscreen questionnaire patient data collection in rheumatology practice:
      development of a highly successful system using process redesign.
AB  - OBJECTIVE: While questionnaires have been developed to capture patient-reported
      outcomes (PROs) in rheumatology practice, these instruments are not widely used.
      We developed a touchscreen interface designed to provide reliable and efficient
      data collection. Using the touchscreen to obtain PROs, we compared 2 different
      workflow models implemented separately in 2 rheumatology clinics. METHODS: The
      Plan-Do-Study-Act methodology was used in 2 cycles of workflow redesign. Cycle 1
      relied on off-the-shelf questionnaire builder software, and cycle 2 relied on a
      custom programmed software solution. RESULTS: During cycle 1, clinic 1 (private
      practice model, resource replete, simple flow) demonstrated a high completion
      rate at the start, averaging between 74% and 92% for the first 12 weeks. Clinic 2
      (academic model, resource deficient, complex flow) did not achieve a consistent
      completion rate above 60%. The revised cycle 2 implementation protocol
      incorporated a 15-minute "nurse visit," an instant messaging system, and a
      streamlined authentication process, all of which contributed to substantial
      improvement in touchscreen questionnaire completion rates of ~80% that were
      sustained without the need for any additional clinic staff support. CONCLUSION:
      Process redesign techniques and touchscreen technology were used to develop a
      highly successful, efficient, and effective process for the routine collection of
      PROs in a busy, complex, and resource-depleted academic practice and in typical
      private practice. The successful implementation required both a touchscreen
      questionnaire, human behavioral redesign, and other technical solutions.

PMID- 22162302
TI  - Use of the Crossboss catheter in coronary chronic total occlusion due to in-stent
      restenosis.
AB  - We describe treatment of six chronic total occlusions due to in-stent restenosis
      with the CrossBoss catheter (BridgePoint Medical, Minneapolis, Minnesota). The
      CrossBoss catheter allowed successful CTO crossing in 5 of 6 lesions (83%): in
      50% the catheter entered the distal true lumen, whereas in 33% a wire was
      required for distal true lumen crossing. No complications were observed. Use of
      the CrossBoss catheter can facilitate treatment of coronary chronic total
      occlusions due to in-stent restenosis.

PMID- 22162303
TI  - Versatile enantioselective [3+2] cyclization between imines and allenoates
      catalyzed by dipeptide-based phosphines.

PMID- 22162305
TI  - Novel cell-penetrating peptides based on alpha-aminoxy acids.
AB  - The remarkable ability of cell-penetrating peptides (CPPs) to deliver cell
      impermeable compounds into living cells makes them attractive transporters for
      use in biology and medicine. Despite their highly efficient cellular uptake, CPPs
      consisting of natural amino acids always suffer from degradation and endosomal
      entrapment, thereby greatly limiting their application in vivo. Here, we describe
      the preparation of novel CPPs incorporating alpha-aminoxy acid residues and their
      cellular uptake behavior. We demonstrate that introducing alpha-aminoxy acids
      into the backbones of CPPs enhances their diffuse cytosolic distribution after
      direct membrane translocation. We also reveal a hybrid peptide, consisting of D
      alpha-aminoxy acids and L-alpha-amino acids, that achieves efficient diffuse
      distribution in the cytosol, is stable toward serum, and possesses low
      cytotoxicity, thus making it a possible vector candidate for in vivo
      applications. Our results confirm that alpha-aminoxy acids are useful building
      blocks when designing novel CPPs possessing favorable properties.

PMID- 22162306
TI  - Tissue engineering based on electrochemical desorption of an RGD-containing
      oligopeptide.
AB  - This paper describes a non-invasive approach for efficient detachment of cells
      adhered to a gold substrate via a specific oligopeptide. Detachment is effected
      by an electrical stimulus. The oligopeptide contains cysteine, which
      spontaneously forms a gold-thiolate bond on a gold surface. This chemical
      adsorption reaches > 95% equilibrium within 10 min after immersion of a gold
      coated substrate in a solution containing the peptide. The peptide is reversibly
      desorbed from the surface within 5 min of application of a negative electrical
      potential. By taking advantage of this simple adsorption and desorption
      mechanism, cells can be grown on an oligopeptide-functionalized gold surface and
      can be efficiently detached as single cells or cell sheets by application of a
      negative electrical potential. This approach was also applied to the surface of
      gold-coated microrods. Capillary-like microchannels were formed in collagen gel
      by transferring endothelial cells to the internal surfaces of the microchannels.
      During subsequent perfusion culture, the enveloped endothelial cells migrated
      into the collagen gel and formed luminal structures, which sprouted from the
      microchannels. This technique has the potential to provide a fundamental tool for
      the engineering of thick cell sheets as well as vascularized tissues and organs.

PMID- 22162307
TI  - Reactive and bioactive cationic alpha-helical polypeptide template for nonviral
      gene delivery.

PMID- 22162308
TI  - Viewpoint: observations on scaled average bioequivalence.
AB  - The two one-sided test procedure (TOST) has been used for average bioequivalence
      testing since 1992 and is required when marketing new formulations of an approved
      drug. TOST is known to require comparatively large numbers of subjects to
      demonstrate bioequivalence for highly variable drugs, defined as those drugs
      having intra-subject coefficients of variation greater than 30%. However, TOST
      has been shown to protect public health when multiple generic formulations enter
      the marketplace following patent expiration. Recently, scaled average
      bioequivalence (SABE) has been proposed as an alternative statistical analysis
      procedure for such products by multiple regulatory agencies. SABE testing
      requires that a three-period partial replicate cross-over or full replicate cross
      over design be used. Following a brief summary of SABE analysis methods applied
      to existing data, we will consider three statistical ramifications of the
      proposed additional decision rules and the potential impact of implementation of
      scaled average bioequivalence in the marketplace using simulation. It is found
      that a constraint being applied is biased, that bias may also result from the
      common problem of missing data and that the SABE methods allow for much greater
      changes in exposure when generic-generic switching occurs in the marketplace.

PMID- 22162309
TI  - CGH arrays compared for DNA isolated from formalin-fixed, paraffin-embedded
      material.
AB  - Formalin-fixed, paraffin-embedded (FFPE) archival tissue is an important source
      of DNA material. The most commonly used technique to identify copy number
      aberrations from chromosomal DNA in tumorigenesis is array comparative genomic
      hybridization (aCGH). Although copy number analysis using DNA from FFPE archival
      tissue is challenging, several research groups have reported high quality and
      reproducible DNA copy number results using aCGH. Aim of this study is to compare
      the commercially available aCGH platforms suitable for high-resolution copy
      number analysis using FFPE-derived DNA. Two dual channel aCGH platforms (Agilent
      and NimbleGen) and a single channel SNP-based platform (Affymetrix) were
      evaluated using seven FFPE colon cancer samples, and median absolute deviation
      (MAD), deflection, signal-to-noise ratio, and DNA input requirements were used as
      quality criteria. Large differences were observed between platforms; Agilent and
      NimbleGen showed better MAD values (0.13 for both) compared with Affymetrix
      (0.22). On the contrary, Affymetrix showed a better deflection of 0.94, followed
      by 0.71 for Agilent and 0.51 for NimbleGen. This resulted in signal-to-nose
      ratios that were comparable between the three commercially available platforms.
      Interestingly, DNA input amounts from FFPE material lower than recommended still
      yielded high quality profiles on all platforms. Copy number analysis using DNA
      derived from FFPE archival material is feasible using all three high-resolution
      copy number platforms and shows reproducible results, also with DNA input amounts
      lower than recommended.

PMID- 22162310
TI  - Polyelectrolyte-functionalized gold nanoparticle scaffold for the sensing of
      heparin and protamine in serum.
AB  - We describe a shape-controlled synthesis of polyelectrolyte-functionalized
      flowerlike and polyhedral Au nanoparticles and the development of a
      nanoarchitectured platform for the selective and highly sensitive detection of
      protamine and heparin by voltammetric, impedimetric, and microgravimetric
      techniques. The functionalized Au nanoparticles were chemically synthesized in
      aqueous solution at room temperature in the presence of the polyelectrolyte
      (either protamine or heparin). The charge on the polyelectrolyte controlled the
      shape and surface morphology of the nanoparticles. The negatively charged heparin
      functionalized Au nanoparticles have multiple branched flowerlike shapes with an
      average size of 50 nm, whereas the cationic protamine-functionalized
      nanoparticles are of polyhedral shape with an average size of 25 nm. Both
      flowerlike and polyhedral nanoparticles have (111), (200), (220), and (311)
      planes of a face-centered cubic lattice of Au. Voltammetric, impedimetric, and
      microgravimetric sensing platforms based on functionalized Au nanoparticles have
      been developed for the sensing of heparin and protamine. The sensing platforms
      are developed by self-assembling the functionalized nanoparticles on a thiol
      functionalized three-dimensional silicate network. The microgravimetric sensing
      platform shows very high sensitivity and it can detect heparin and protamine at
      concentrations as low as 0.05 MUg mL(-1). The selectivity of the sensing platform
      towards heparin was examined with potential interferents such as hyaluronic acid
      (HA) and chondroitin-4-sulfate (CS). Both HA and CS did not interfere with the
      measurement of heparin. The practical application of the sensing platform was
      demonstrated by measuring the concentration of heparin and protamine in human
      serum samples. The sensing platform could successfully quantify the concentration
      of heparin and protamine in the real serum samples with excellent recovery. The
      sensing platform was robust and could be used for repeated measurement without
      compromising the sensitivity.

PMID- 22162311
TI  - Genistein mitigates radiation-induced testicular injury.
AB  - The present study investigated the radioprotective effect of a multifunctional
      soy isoflavone, genistein, with the testicular system. Genistein was administered
      (200 mg/kg body weight) to male C3H/HeN mice by subcutaneous injection 24 h prior
      to pelvic irradiation (5 Gy). Histopathological parameters were evaluated 12 h
      and 21 days post-irradiation. Genistein protected the germ cells from radiation
      induced apoptosis (p < 0.05 vs vehicle-treated irradiated mice at 12 h post
      irradiation). Genistein significantly attenuated radiation-induced reduction in
      testis weight, seminiferous tubular diameter, seminiferous epithelial depth and
      sperm head count in the testes (p < 0.05 vs vehicle-treated irradiated mice at 21
      days post-irradiation). Repopulation and stem cell survival indices of the
      seminiferous tubules were increased in the genistein-treated group compared with
      the vehicle-treated irradiation group at 21 days post-irradiation (p < 0.01). The
      irradiation-mediated decrease in the sperm count and sperm mobility in the
      epididymis was counteracted by genistein (p < 0.01), but no effect on the
      frequency of abnormal sperm was evident. Reactive oxygen species (ROS) were
      evaluated using DCFDA method and exposure to irradiation elevated ROS levels in
      the testis and genistein treatment resulted in a significant attenuation of
      radiation-induced ROS production. The results indicate that genistein protects
      from testicular dysfunction induced by gamma-irradiation by an antiapoptotic
      effect and recovery of spermatogenesis.

PMID- 22162312
TI  - From the Feist-Benary reaction to organocatalytic domino Michael-alkylation
      reactions: asymmetric synthesis of 3(2H)-furanones.

PMID- 22162313
TI  - Predicting concentrations of trace organic compounds in municipal wastewater
      treatment plant sludge and biosolids using the PhATETM model.
AB  - This article presents the capability expansion of the PhATETM (pharmaceutical
      assessment and transport evaluation) model to predict concentrations of trace
      organics in sludges and biosolids from municipal wastewater treatment plants
      (WWTPs). PhATE was originally developed as an empirical model to estimate
      potential concentrations of active pharmaceutical ingredients (APIs) in US
      surface and drinking waters that could result from patient use of medicines.
      However, many compounds, including pharmaceuticals, are not completely
      transformed in WWTPs and remain in biosolids that may be applied to land as a
      soil amendment. This practice leads to concerns about potential exposures of
      people who may come into contact with amended soils and also about potential
      effects to plants and animals living in or contacting such soils. The model
      estimates the mass of API in WWTP influent based on the population served, the
      API per capita use, and the potential loss of the compound associated with human
      use (e.g., metabolism). The mass of API on the treated biosolids is then
      estimated based on partitioning to primary and secondary solids, potential loss
      due to biodegradation in secondary treatment (e.g., activated sludge), and
      potential loss during sludge treatment (e.g., aerobic digestion, anaerobic
      digestion, composting). Simulations using 2 surrogate compounds show that
      predicted environmental concentrations (PECs) generated by PhATE are in very good
      agreement with measured concentrations, i.e., well within 1 order of magnitude.
      Model simulations were then carried out for 18 APIs representing a broad range of
      chemical and use characteristics. These simulations yielded 4 categories of
      results: 1) PECs are in good agreement with measured data for 9 compounds with
      high analytical detection frequencies, 2) PECs are greater than measured data for
      3 compounds with high analytical detection frequencies, possibly as a result of
      as yet unidentified depletion mechanisms, 3) PECs are less than analytical
      reporting limits for 5 compounds with low analytical detection frequencies, and
      4) the PEC is greater than the analytical method reporting limit for 1 compound
      with a low analytical detection frequency, possibly again as a result of
      insufficient depletion data. Overall, these results demonstrate that PhATE has
      the potential to be a very useful tool in the evaluation of APIs in biosolids.
      Possible applications include: prioritizing APIs for assessment even in the
      absence of analytical methods; evaluating sludge processing scenarios to explore
      potential mitigation approaches; using in risk assessments; and developing
      realistic nationwide concentrations, because PECs can be represented as a
      cumulative probability distribution. Finally, comparison of PECs to measured
      concentrations can also be used to identify the need for fate studies of
      compounds of interest in biosolids.

PMID- 22162314
TI  - Angiotensin II type 2 receptor is critical for the development of human fetal
      pancreatic progenitor cells into islet-like cell clusters and their potential for
      transplantation.
AB  - Local renin-angiotensin systems (RASs) regulate the differentiation of tissue
      progenitors. However, it is not known whether such systems can regulate the
      development of pancreatic progenitor cells (PPCs). To address this issue, we
      characterized the expression profile of major RAS components in human fetal PPC
      preparations and examined their effects on the differentiation of PPCs into
      functional islet-like cell clusters (ICCs). We found that expression of RAS
      components was highly regulated throughout PPC differentiation and that locally
      generated angiotensin II (Ang II) maintained PPC growth and differentiation via
      Ang II type 1 and type 2 (AT(1) and AT(2)) receptors. In addition, we observed
      colocalization of AT(2) receptors with critical beta-cell phenotype markers in
      PPCs/ICCs, as well as AT(2) receptor upregulation during differentiation,
      suggesting that these receptors may regulate beta-cell development. In fact, we
      found that AT(2) , but not AT(1) , receptor was a key mediator of Ang II-induced
      upregulation of transcription factors important in beta-cell development.
      Furthermore, lentivirus-mediated knockdown of AT(2) receptor suppressed the
      expression of these transcription factors in ICCs. Transplantation of AT(2)
      receptor-depleted ICCs into immune-privileged diabetic mice failed to ameliorate
      hyperglycemia, implying that AT(2) receptors are indispensable during ICC
      maturation in vivo. These data strongly indicate that a local RAS is involved in
      governing the functional maturation of pancreatic progenitors toward the
      endocrine lineage.

PMID- 22162315
TI  - Dynamic culture induces a cell type-dependent response impacting on the thickness
      of engineered connective tissues.
AB  - Mesenchymal cells are central to connective tissue homeostasis and are widely
      used for tissue-engineering applications. Dermal fibroblasts and adipose-derived
      stromal cells (ASCs) allow successful tissue reconstruction by the self-assembly
      approach of tissue engineering. This method leads to the production of
      multilayered tissues, devoid of exogenous biomaterials, that can be used as
      stromal compartments for skin or vesical reconstruction. These tissues are formed
      by combining cell sheets, generated through cell stimulation with ascorbic acid,
      which favours the cell-derived production/organization of matrix components.
      Since media motion can impact on cell behaviour, we investigated the effect of
      dynamic culture on mesenchymal cells during tissue reconstruction, using the self
      assembly method. Tissues produced using ASCs in the presence of a wave-like
      movement were nearly twice thicker than under standard conditions, while no
      difference was observed for tissues produced from dermal fibroblasts. The
      increased matrix deposition was not correlated with an increased proliferation of
      ASCs, or by higher transcript levels of fibronectin or collagens I and III. A 30%
      increase of type V collagen mRNA was observed. Interestingly, tissues engineered
      from dermal fibroblasts featured a four-fold higher level of MMP-1 transcripts
      under dynamic conditions. Mechanical properties were similar for tissues
      reconstructed using dynamic or static conditions. Finally, cell sheets produced
      using ASCs under dynamic conditions could readily be manipulated, resulting in a
      2 week reduction of the production time (from 5 to 3 weeks). Our results describe
      a distinctive property of ASCs' response to media motion, indicating that their
      culture under dynamic conditions leads to optimized tissue engineering.

PMID- 22162316
TI  - Bioorthogonal reaction pairs enable simultaneous, selective, multi-target
      imaging.

PMID- 22162317
TI  - Modelling and simulation in the pharmaceutical industry--some reflections.
AB  - Modelling and simulation (M&S) is increasingly being applied in (clinical) drug
      development. It provides an opportune area for the community of pharmaceutical
      statisticians to pursue. In this article, we highlight useful principles behind
      the application of M&S. We claim that M&S should be focussed on decisions,
      tailored to its purpose and based in applied sciences, not relying entirely on
      data-driven statistical analysis. Further, M&S should be a continuous process
      making use of diverse information sources and applying Bayesian and frequentist
      methodology, as appropriate. In addition to forming a basis for analysing
      decision options, M&S provides a framework that can facilitate communication
      between stakeholders. Besides the discussion on modelling philosophy, we also
      describe how standard simulation practice can be ineffective and how simulation
      efficiency can often be greatly improved.

PMID- 22162318
TI  - Rasta resin-PPh3-NBniPr2 and its use in one-pot Wittig reaction cascades.
AB  - A new triarylphosphine-tertiary amine bifunctional polymeric reagent has been
      prepared and used effectively in a variety of one-pot Wittig reactions. The
      design of this reagent resolved a deficiency of a previously reported related
      material, and allowed it to perform more efficiently in such reactions.
      Furthermore, it was readily recyclable, and was also successfully applied in
      cascade processes involving one-pot Wittig reactions followed by either a
      conjugate reduction or a reductive aldol reaction. In these reaction cascades,
      the phosphine oxide groups generated in the Wittig reaction served as the
      catalyst for the subsequent reaction.

PMID- 22162319
TI  - Injection of paraoxonase 1 (PON1) to mice stimulates their HDL and macrophage
      antiatherogenicity.
AB  - We analyzed, for the first time, the effects of recombinant PON1 (rePON1)
      intraperitoneal injection to C57BL/6 mice on their HDL and macrophage
      antiatherogenic properties. Thioglycolate-treated mice were injected with either
      saline (Control), or rePON1 (50 MUg/mouse), and 20 H post injection, their blood
      samples and peritoneal macrophages (MPM) were collected. A significant increase
      in serum and HDL-PON1 arylesterase and lactonase activities was noted. Similarly,
      a significant increment, by 3.8 and 2.8 fold, in MPM-PON1 arylesterase and
      lactonase activities, respectively, as compared to the activities in control MPM
      was observed. The HDL from rePON1-injected mice was resistant to oxidation by
      copper ions as compared to control HDL. Furthermore, enrichment of the mouse HDL
      with rePON1 increased its ability to induce cholesterol efflux from J774A.1
      macrophage cell line, and to inhibit macrophage-mediated LDL oxidation. In MPM
      from rePON1-injected mice vs. control MPM, there was a significant reduction in
      cholesterol mass, by 42%, in association with inhibition in cellular cholesterol
      biosynthesis rate, by 33%, and with significant stimulation, by 65%, of human HDL
      mediated cholesterol efflux from the cells. We conclude that rePON1 injection to
      mice improved the mice HDL and MPM antiatherogenic properties, and these effects
      could probably lead to attenuation of atherosclerosis development.

PMID- 22162320
TI  - Electron correlation in real time.
AB  - Electron correlation, caused by the interaction among electrons in a
      multielectron system, manifests itself in all states of matter. A complete
      theoretical description of interacting electrons is challenging; different
      approximations have been developed to describe the fundamental aspects of the
      correlation that drives the evolution of simple (few-electron systems in
      atoms/molecules) as well as complex (multielectron wave functions in atoms,
      molecules, and solids) systems. Electron correlation plays a key role in the
      relaxation mechanisms that characterize excited states of neutral or ionized
      atoms and molecules populated by absorption of extreme ultraviolet (XUV) or X-ray
      radiation. The dynamics of these states can lead to different processes such as
      Fano resonance and Auger decay in atoms or interatomic Coulombic decay or charge
      migration in molecules and clusters. Many of these relaxation mechanisms are
      ubiquitous in nature and characterize the interaction of complex systems, such as
      biomolecules, adsorbates on surfaces, and hydrogen-bonded clusters, with XUV
      light. These mechanisms evolve typically on the femtosecond (1 fs=10(-15)  s) or
      sub-femtosecond timescale. The experimental availability of few-femtosecond and
      attosecond (1 as=10(-18)  s) XUV pulses achieved in the last 10 years offers, for
      the first time, the opportunity to excite and probe in time these dynamics giving
      the possibility to trace and control multielectron processes. The generation of
      ultrashort XUV radiation has triggered the development and application of
      spectroscopy techniques that can achieve time resolution well into the attosecond
      domain, thereby offering information on the correlated electronic motion and on
      the correlation between electron and nuclear motion. A deeper understanding of
      how electron correlation works could have a large impact in several research
      fields, such as biochemistry and biology, and trigger important developments in
      the design and optimization of electronic devices.

PMID- 22162323
TI  - Fundamental research needs excellent scientists and its own space.

PMID- 22162321
TI  - Copper(I) enolate complexes in alpha-arylation reactions: synthesis, reactivity,
      and mechanism.

PMID- 22162324
TI  - Physical aspects of cell culture substrates: topography, roughness, and
      elasticity.
AB  - The cellular environment impacts a myriad of cellular functions by providing
      signals that can modulate cell phenotype and function. Physical cues such as
      topography, roughness, gradients, and elasticity are of particular importance.
      Thus, synthetic substrates can be potentially useful tools for exploring the
      influence of the aforementioned physical properties on cellular function. Many
      micro- and nanofabrication processes have been employed to control substrate
      characteristics in both 2D and 3D environments. This review highlights strategies
      for modulating the physical properties of surfaces, the influence of these
      changes on cell responses, and the promise and limitations of these surfaces in
      in-vitro settings. While both hard and soft materials are discussed, emphasis is
      placed on soft substrates. Moreover, methods for creating synthetic substrates
      for cell studies, substrate properties, and impact of substrate properties on
      cell behavior are the main focus of this review.

PMID- 22162325
TI  - Double-vessel coronary stenting via 5 French diagnostic catheters.
AB  - The authors report on the use of 5 French diagnostic catheters to deliver a stent
      on-a-wire system during a double vessel coronary intervention.

PMID- 22162326
TI  - Toxicological risks to humans of toxaphene residues in fish.
AB  - A revised risk assessment for toxaphene was developed, based on the assumption
      that fish consumers are only exposed to toxaphene residues that differ
      substantially from technical toxaphene due to environmental degradation and
      metabolism. In vitro studies confirmed that both technical toxaphene and degraded
      toxaphene inhibit gap junctional intercellular communication that correlates with
      the mechanistic potential to cause tumor promotion. In vivo rat studies
      established the NOAEL for degraded and technical toxaphene at the highest dose
      tested in the bioassay. Toxaphene residue intakes from European fishery products
      were estimated and compared to the provisional tolerable daily intakes (TDIs)
      from various regulatory agencies including Canada, the United States, and
      Germany. The estimated intake was also compared to a new calculated provisional
      MATT pTDI. The MATT pTDI is based on new toxicological information (in vivo rat
      studies) developed on a model for environmental toxaphene residues rather than
      technical toxaphene. A MATT pTDI (1.08 mg total toxaphene for a person of 60 kg)
      for tumor promotion potency was adopted for use in Europe and is referred to here
      as the MATT pTDI. These new data result in a better estimate of safety and a
      higher TDI than previously used. Based on realistic fish consumption data and
      recent baseline concentration data of toxaphene in European fishery products, the
      toxaphene intake for the consumers of Germany, Ireland, Norway, and the
      Netherlands was estimated. For an average adult fish consumer, the average daily
      intake of toxaphene was estimated to be 1.2, 0.4, 0.5, and 0.2 ug for the
      consumers of Norway, Germany, Ireland, and the Netherlands, respectively. The
      toxaphene intake of these average fish consumers was far below the MATT pTDI of
      1.08 mg/60 kg bw. In conclusion, based on the most relevant toxicological studies
      and the most realistic estimates of fish consumption and recent concentrations of
      toxaphene in European fishery products, adverse health effects are unlikely for
      the average European consumer of fishery products. In no case is the MATT pTDI
      exceeded.

PMID- 22162327
TI  - Donor-acceptor ring-in-ring complexes.
AB  - The self-assembly of three donor-acceptor ring-in-ring complexes, prepared from
      the pi-electron-deficient tetracationic cyclophane, cyclobis(paraquat-4,4'
      biphenylene), and three large pi-electron-rich crown ethers (each 50-membered
      rings) containing dioxynaphthalene (DNP) and tetrathiafulvalene (TTF) units in
      pairs (DNP/DNP, DNP/TTF and TTF/TTF), is reported. (1)H NMR spectroscopic
      analyses are indicative of the formation of 1:1 complexes in CD(3)CN, whilst the
      charge-transfer interactions between the DNP and TTF units of the crown ethers
      and the tetracationic cyclophane have permitted the measurement of binding
      constants of up to 4*10(3) M(-1) in CH(3)CN to be made using UV/Vis spectroscopy.
      Ring-in-ring complexes are proposed as intermediates in the stepwise synthesis of
      molecular Borromean rings (BRs) comprised of three different rings. With the
      particular choice of crown ethers, the 1:1 complexes have polyether loops that
      protrude from the donor-acceptor recognition point above and below the mean plane
      of the tetracationic cyclophane, which, ideally, could conceivably bind
      dialkylammonium centers present in a third ring. X-ray crystallographic analyses
      of the solid-state superstructures of two of the three 1:1 complexes reveal,
      however, the presence of prodigious CH...O interactions between the polyether
      loops of the crown ethers and the rims of the cyclophane, no doubt stabilizing
      the complexes, but, at the same time, masking their potential recognition sites
      from further interactions that are essential to the subsequent emergence of the
      third ring. The solid-state superstructure of one of the crown ethers binding two
      dibenzylammonium ions provides some insight into the design requirements for the
      next generation of these systems; longer polyether loops may be required to allow
      optimal interactions between all components. It has become clear during a pursuit
      of the stepwise synthesis of the molecular BRs that, when designing complex
      mechanically interlocked molecules utilizing multiple recognition sites, the
      unsullied orthogonality of the recognition motifs is of the utmost importance.

PMID- 22162328
TI  - Vacuum thrombectomy of large right atrial thrombus.
AB  - We report a novel technique for percutaneous removal of the right heart thrombi
      using a suction cannula. This method allowed complete en bloc removal of the
      right atrial thrombus avoiding surgical procedure in a high risk patient.

PMID- 22162329
TI  - Evaluation of platelet-rich plasma and hydrostatic pressure regarding cell
      differentiation in nucleus pulposus tissue engineering.
AB  - Generation of a biological nucleus pulposus (NP) replacement by tissue
      engineering appears to be a promising approach for the therapy of early stages of
      intervertebral disc degeneration. Thereby, autologous mesenchymal stem cells
      (MSCs) represent an attractive cell source compared to cells of the NP that are
      already altered in their phenotype due to degenerative processes. This study
      compares the influence of 3D pellet culture and alginate beads, as well as that
      of different media compositions, by the addition of human platelet-rich plasma
      (PRP) or transforming growth factor (TGF-beta1 ) in interaction with hydrostatic
      pressure on chondrogenic differentiation of human MSCs compared to NP cells. We
      found that gene expression of the chondrogenic markers aggrecan, collagen type 2
      and collagen type 1 and Sox9 was considerably lower in cells cultivated with PRP
      compared to TGF-beta1 . Immunohistology confirmed this result at protein level in
      pellet culture. Additionally, the pellet culture system was found to be more
      suitable than alginate beads. A positive influence of hydrostatic pressure could
      only be shown for individual donors. In summary, in comparison to TGF-beta1 ,
      human PRP did not induce adequate chondrogenic differentiation for both culture
      systems and cell types used. The mixture of growth factors in PRP promoted
      proliferation rather than chondrogenic differentiation. Based on these results,
      an application of PRP in human NP tissue-engineering approaches cannot be
      recommended.

PMID- 22162330
TI  - Nonclassical tunability of solid-state CD and CPL properties of a chiral 2
      naphthalenecarboxylic acid/amine supramolecular organic fluorophore.
AB  - The solid-state chiral optical properties (circular dichroism and circularly
      polarized luminescence) of a 2-naphthalenecarboxylic acid/amine supramolecular
      organic fluorophore can be controlled by changing the aryl unit of the chiral 1
      arylethylamine component of the molecule rather than altering the chirality of
      the 1-arylethylamine itself.

PMID- 22162331
TI  - Anchored proteinase-targetable optomagnetic nanoprobes for molecular imaging of
      invasive cancer cells.

PMID- 22162332
TI  - Distinguishing human cell types based on housekeeping gene signatures.
AB  - 'In this report, we use single cell gene expression to identify transcriptional
      patterns emerging during the differentiation of human embryonic stem cells
      (hESCs) into the endodermal lineage. Endoderm-specific transcripts are highly
      variable between individual CXCR4(+) endodermal cells, suggesting that either the
      cells generated from in vitro differentiation are distinct or that these
      embryonic cells tolerate a high degree of transcript variability. Housekeeping
      transcripts, on the other hand, are far more consistently expressed within the
      same cellular population. However, when we compare the levels of housekeeping
      transcripts between hESCs and derived endoderm, patterns emerge that can be used
      to clearly separate the two embryonic cell types. We further compared four
      additional human cell types, including 293T, induced pluripotent stem cell
      (iPSC), HepG2, and endoderm-derived iPSC. In each case, the relative levels of
      housekeeping transcripts defined a particular cell fate. Interestingly, we find
      that three transcripts, LDHA, NONO, and ACTB, contribute the most to this
      diversity and together serve to segregate all six cell types. Overall, this
      suggests that levels of housekeeping transcripts, which are expressed within all
      cells, can be leveraged to distinguish between human cell types and thus may
      serve as important biomarkers for stem cell biology and other disciplines.

PMID- 22162333
TI  - Structure of the B4 liquid crystal phase near a glass surface.
AB  - The B4 liquid crystal phase of bent-core molecules, a smectic phase of helical
      nanofilaments, is one of the most complex hierarchical self-assemblies in soft
      materials. We describe the layer topology of the B4 phase of mesogens in the P-n
      OPIMB homologous series near the liquid crystal/glass interface. Freeze-fracture
      transmission electron microscopy reveals that the twisted layer structure of the
      bulk is suppressed, the layers instead forming a structure with periodic layer
      undulations, with the topography depending on the distance from the glass. The
      surface layer structure is modeled as parabolic focal conic arrays generated by
      equidistant parabolas whose foci are defect lines along the glass surface.
      Nucleation and growth of toric focal conics near the glass substrate is also
      observed. Although the growth of twisted nanofilaments, the usual manifestation
      of structural chirality in the B4 phase, is suppressed near the surface, the
      smectic layers are intrinsically chiral, and the helical filaments that form on
      top of them grow with specific handedness.

PMID- 22162334
TI  - Room-temperature synthesis of air-stable and size-tunable luminescent ZnS-coated
      Cd3P2 nanocrystals with high quantum yields.

PMID- 22162335
TI  - Inhibition of glycoprotein synthesis in the endoplasmic reticulum as a novel
      anticancer mechanism of (-)-epigallocatechin-3-gallate.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) has been found to trigger the unfolded
      protein response (UPR) likely due to the inhibition of glucosidase II, a key
      enzyme of glycoprotein processing and quality control in the endoplasmic
      reticulum (ER). These findings strongly suggest that EGCG interferes with
      glycoprotein maturation and sorting in the ER. This hypothesis was tested in SK
      Mel28 human melanoma cells by assessing the effect of EGCG and deoxynojirimycin
      (DNJ) on the synthesis of two endogenous glycoproteins. Both tyrosinase and
      vascular endothelial growth factor (VEGF) protein levels were remarkably reduced
      despite unaltered mRNA expression in EGCG- or DNJ-treated cells compared to
      control. The hindrance of tyrosinase and VEGF protein synthesis could be
      prevented by proteasome inhibitor, lactacystine. Collectively, our results
      support that glucosidase II inhibitor EGCG interferes with protein processing and
      quality control in the ER, which diverts tyrosinase, VEGF, and likely other
      glycoproteins towards proteasomal degradation. This mechanism provides a novel
      therapeutic approach in dermatology and might play an important role in the
      antitumor effect or hepatotoxicity of EGCG.

PMID- 22162336
TI  - A statistician's perspective on biomarkers in drug development.
AB  - Biomarkers play an increasingly important role in many aspects of pharmaceutical
      discovery and development, including personalized medicine and the assessment of
      safety data, with heavy reliance being placed on their delivery. Statisticians
      have a fundamental role to play in ensuring that biomarkers and the data they
      generate are used appropriately and to address relevant objectives such as the
      estimation of biological effects or the forecast of outcomes so that claims of
      predictivity or surrogacy are only made based upon sound scientific arguments.
      This includes ensuring that studies are designed to answer specific and pertinent
      questions, that the analyses performed account for all levels and sources of
      variability and that the conclusions drawn are robust in the presence of
      multiplicity and confounding factors, especially as many biomarkers are
      multidimensional or may be an indirect measure of the clinical outcome. In all of
      these areas, as in any area of drug development, statistical best practice
      incorporating both scientific rigor and a practical understanding of the
      situation should be followed. This article is intended as an introduction for
      statisticians embarking upon biomarker-based work and discusses these issues from
      a practising statistician's perspective with reference to examples.

PMID- 22162337
TI  - Branched and 4-arm starlike alpha-helical peptide structures with enhanced
      antimicrobial potency and selectivity.

PMID- 22162339
TI  - "They didn't tell us, they made us work it out ourselves": patient perspectives
      of a cognitive-behavioral program for rheumatoid arthritis fatigue.
AB  - OBJECTIVE: Fatigue is an overwhelming rheumatoid arthritis (RA) symptom caused by
      interacting clinical and psychosocial factors. Cognitive-behavioral therapy (CBT)
      addresses links between thoughts, feelings, and behaviors and uses cognitive
      restructuring to facilitate behavior changes. In a randomized controlled trial, a
      group CBT program for RA fatigue improved fatigue impact, severity, and perceived
      coping, as well as mood and quality of life. The aim of this study was to explore
      the patient perspective of the program and the impact of behavior changes.
      METHODS: Ten exit focus groups were held (38 patients). Transcripts were analyzed
      by an independent researcher using a hybrid thematic approach, with a subset
      analyzed by a team member and patient partner. RESULTS: Three overarching themes
      were identified. In "they made us work it out ourselves" (program factors
      facilitating changes), patients spontaneously identified elements of group CBT as
      pivotal, including guided discovery, the impact of metaphors, and working as a
      group. In "feeling much better about yourself and coping much better" (the nature
      of changes), patients described cognitive changes, including enhanced self
      efficacy and problem solving, and emotional changes, including being less
      volatile and fearful of fatigue. In "my life has changed so much it's
      unbelievable" (benefits beyond fatigue), patients reengaged in previously
      abandoned activities, were more active, and enjoyed greater social participation.
      CONCLUSION: Patients highlighted that CBT elements were key to making behavior
      changes and that these had far-reaching impacts on their lives. This suggests it
      could be beneficial in clinical practice to incorporate cognitive-behavioral
      approaches into patient education programs that aim to enhance self-management.

PMID- 22162340
TI  - An 800  kb deletion at 17q23.2 including the MED13 (THRAP1) gene, revealed by
      aCGH in a patient with a SMC 17p.
AB  - We report on clinical and cytogenetic studies in a 7-year-old child with moderate
      intellectual disability, short stature, mild dysmorphism, and hearing loss. R
      chromosome banding showed a de novo autosomal marker originating from the 17p
      chromosome segment in all cells analyzed. Array comparative genome hybridization
      (aCGH) was used to determine the gene content and proximal and distal breakpoints
      of the small supernumerary marker chromosome (SMC). These breakpoints mapped to
      the centromere of chromosome 17 and the 17p11.2 region, respectively.
      Unexpectedly, aCGH analysis also revealed a de novo deletion of 800 kb
      encompassing six genes in the 17q23.2 region, including MED13 (also known as
      THRAP1). We compared our patient with other reported cases of SMC(17), to
      determine the respective contributions of the duplication and the deletion to the
      phenotype. We cannot entirely exclude a minor role for the SMC(17), but we
      suggest that MED13 haploinsufficiency was responsible for the phenotype of the
      patient particularly the cataract, hearing loss and semicircular canal dysplasia.
      Moreover, this report highlights the usefulness of aCGH for the specification of
      gene content in cases of abnormality, facilitating the establishment of accurate
      phenotype-genotype correlations and the detection of other, complex
      rearrangements.

PMID- 22162341
TI  - Acute ST changes during anesthesia induction 10 months after Norwood procedure.
AB  - After the Norwood procedure for palliation of hypoplastic left heart syndrome,
      there is still significant interstage and late mortality with often unclear
      etiology. An important, but possibly under-recognized complication of the Norwood
      operation is the potential for coronary insufficiency from pre-coronary stenosis
      due to kinking or scarring at the anastomosis between the native and neo-aorta.
      We report a case of a clinically thriving 10-month old infant status post
      bidirectional Glenn who had acute ischemic changes on electrocardiogram (ECG)
      during induction of anesthesia for elective bilateral herniorrhaphy. A discrete
      narrowing in the native aorta to neo-aorta anastomosis was identified. A stent
      was placed emergently to restore adequate coronary blood flow after failure of
      simple angioplasty to adequately improve the stenosis.

PMID- 22162342
TI  - Immunocytochemical colocalization of P16(INK4a) and Ki-67 predicts CIN2/3 and
      AIS/adenocarcinoma.
AB  - BACKGROUND: Although previous studies have shown that p16(INK4a) and Ki-67 are
      sensitive and specific markers for high-grade lesions (>=CIN2) on cervical
      biopsies, limited information is available regarding the performance of a dual
      staining approach as a diagnostic adjunct in cervical cytology. We evaluated a
      dual p16(INK4a)/Ki-67 immunocytochemistry (ICC) assay to determine its
      sensitivity and specificity versus that of high-risk HPV (HR-HPV) in a US-based
      pilot cytology study. METHODS: ThinPrep specimens from 122 cervical cytology
      specimens encompassing 23 negative (NILM), 20 ASC-US, 22 LSIL, 17 ASCH, 22 HSIL,
      and 18AGC cases were processed for multiplexed ICC staining using a CINtec Plus
      Kit. Dual-positive assay results were defined based on the detection of 1 or more
      epithelial cells that were stained for both p16INK4a and Ki-67 without regard to
      cellular morphology. HR-HPV testing was performed by multiplex PCR with capillary
      electrophoresis genotyping. RESULTS: Dual staining for p16(INK4a) and Ki-67 was
      frequently detected in HSIL and AGC but was rarely detected in NILM cases. The HR
      HPV assay showed a sensitivity of 76.2% and a specificity of 55.8% for the
      detection of clinically significant cervical squamous or endometrial lesions. In
      contrast, the colocalization of p16(INK4a) plus Ki-67 maintained a high
      sensitivity of 81.8% and improved specificity to 81.8% for biopsy-confirmed
      CIN2/3, endocervical adenocarcinoma, or endometrial adenocarcinoma. CONCLUSIONS:
      Dual staining for p16(INK4a)/Ki-67 immunocytochemistry dramatically increased
      specificity and maintained high-level sensitivity for the diagnosis of CIN2/3 or
      glandular lesions compared with PCR-based testing for HR-HPV.

PMID- 22162344
TI  - 12- to 22-membered bridged beta-lactams as potential penicillin-binding protein
      inhibitors.
AB  - As potential inhibitors of penicillin-binding proteins (PBPs), we focused our
      research on the synthesis of non-traditional 1,3-bridged beta-lactams embedded
      into macrocycles. We synthesized 12- to 22-membered bicyclic beta-lactams by the
      ring-closing metathesis (RCM) of bis-omega-alkenyl-3(S)-aminoazetidinone
      precursors. The reactivity of 1,3-bridged beta-lactams was estimated by the
      determination of the energy barrier of a concerted nucleophilic attack and lactam
      ring-opening process by using ab initio calculations. The results predicted that
      16-membered cycles should be more reactive. Biochemical evaluations against R39
      DD-peptidase and two resistant PBPs, namely, PBP2a and PBP5, revealed the
      inhibition effect of compound 4d, which featured a 16-membered bridge and the N
      tert-butyloxycarbonyl chain at the C3 position of the beta-lactam ring.
      Surprisingly, the corresponding bicycle, 12d, with the PhOCH(2)CO side chain at
      C3 was inactive. Reaction models of the R39 active site gave a new insight into
      the geometric requirements of the conformation of potential ligands and their
      steric hindrance; this could help in the design of new compounds.

PMID- 22162343
TI  - Lack of a p21waf1/cip -dependent G1/S checkpoint in neural stem and progenitor
      cells after DNA damage in vivo.
AB  - The cyclin-dependent kinase inhibitor p21(waf1/cip) mediates the p53-dependent
      G1/S checkpoint, which is generally considered to be a critical requirement to
      maintain genomic stability after DNA damage. We used staggered 5-ethynyl
      2'deoxyuridine/5-bromo-2'-deoxyuridine double-labeling in vivo to investigate the
      cell cycle progression and the role of p21(waf1/cip) in the DNA damage response
      of neural stem and progenitor cells (NSPCs) after exposure of the developing
      mouse cortex to ionizing radiation. We observed a radiation-induced p21-dependent
      apoptotic response in migrating postmitotic cortical cells. However, neural stem
      and progenitor cells (NSPCs) did not initiate a p21(waf1/cip1) -dependent G1/S
      block and continued to enter S-phase at a similar rate to the non-irradiated
      controls. The G1/S checkpoint is not involved in the mechanisms underlying the
      faithful transmission of the NSPC genome and/or the elimination of critically
      damaged cells. These processes typically involve intra-S and G2/M checkpoints
      that are rapidly activated after irradiation. p21 is normally repressed in neural
      cells during brain development except at the G1 to G0 transition. Lack of
      activation of a G1/S checkpoint and apoptosis of postmitotic migrating cells
      after DNA damage appear to depend on the expression of p21 in neural cells, since
      substantial cell-to-cell variations are found in the irradiated cortex. This
      suggests that repression of p21 during brain development prevents the induction
      of the G1/S checkpoint after DNA damage.

PMID- 22162345
TI  - Total synthesis of carolacton, a highly potent biofilm inhibitor.

PMID- 22162346
TI  - Automatic conformal prescription of very selective saturation bands for in vivo
      1H-MRSI of the prostate.
AB  - An important step in the implementation of three-dimensional in vivo proton
      magnetic resonance spectroscopic imaging ((1)H-MRSI) of the prostate is the
      placement of spatial saturation pulses around the region of interest (ROI) for
      the removal of unwanted contaminating signals from peripheral tissue. The present
      study demonstrates the use of a technique called conformal voxel magnetic
      resonance spectroscopy (CV-MRS). This method automates the placement,
      orientation, timing and flip angle of very selective saturation (VSS) pulses
      around an irregularly-shaped, user-defined ROI. The method employs a user
      adjustable number of automatically positioned VSS pulses (20 used in the present
      study) which null the signal from periprostatic lipids while closely conforming
      the shape of the excitation voxel to the shape of the prostate. A standard
      endorectal coil in combination with a torso-phased array coil was used for all in
      vivo prostate studies. Three-dimensional in vivo prostate (1)H-MRSI data were
      obtained using the proposed semi-automated CV-MRS technique, and compared with a
      standard point resolved spectroscopy (PRESS) technique at TE = 130 ms using
      manual placement of saturation pulses. The in vivo prostate (1)H-MRSI data
      collected from 12 healthy subjects using the CV-MRS method showed significantly
      reduced lipid contamination throughout the prostate, and reduced baseline
      distortions. On average there was a 50 +/- 17% (range 12% - 68%) reduction in
      lipids throughout the prostate. A voxel-by-voxel benchmark test of over 850
      voxels showed that there were 63% more peaks fitted using the LCModel when using
      a Cramer-Rao Lower Bound (CRLB) cut-off of 40% when using the optimized conformal
      voxel technique in comparison to the manual placement approach. The evaluation of
      this CV-MRS technique has demonstrated the potential for easy automation of the
      graphical prescription of saturation bands for use in (1)H-MRSI.

PMID- 22162347
TI  - At the border of intermetallic compounds and transition-metal oxides: crystal
      intergrowth of the Zintl phase Cs4Ge9 and Cs2WO4 or Cs3VO4 as well as nine-atom
      cluster relocation in the solid state.

PMID- 22162348
TI  - Curtailed two-stage designs with two dependent binary endpoints.
AB  - When phase I clinical trials were found to be unable to precisely estimate the
      frequency of toxicity, Brayan and Day proposed incorporating toxicity
      considerations into two-stage designs in phase II clinical trials. Conaway and
      Petroni further pointed out that it is important to evaluate the clinical
      activity and safety simultaneously in studying cancer treatments with more toxic
      chemotherapies in a phase II clinical trial. Therefore, they developed multi
      stage designs with two dependent binary endpoints. However, the usual sample
      sizes in phase II trials make these designs difficult to control the type I error
      rate at a desired level over the entire null region and still have sufficient
      power against reasonable alternatives. Therefore, the curtailed sampling
      procedure summarized by Phatak and Bhatt will be applied to the two-stage designs
      with two dependent binary endpoints in this paper to reduce sample sizes and
      speed up the development process for drugs.

PMID- 22162355
TI  - Morphology controlled nanostructures self-assembled from phthalocyanine
      derivatives bearing alkylthio moieties: effect of sulfur-sulfur and metal-ligand
      coordination on intermolecular stacking.
AB  - To investigate the effect of sulfur-sulfur and metal-ligand coordination on the
      molecular structure and morphology of self-assembled nanostructures, metal-free
      2,3,9,10,16,17,23,24-octakis(isopropylthio)phthalocyanine H(2)Pc(beta
      SC(3)H(7))(8) (1) and its copper and lead congeners CuPc(beta-SC(3)H(7))(8) (2)
      and PbPc(beta-SC(3)H(7))(8) (3) are synthesized and fabricated into organic
      nanostructures by a phase-transfer method. The self-assembly properties are
      investigated by electronic absorption and Fourier transform infrared (FTIR)
      spectroscopy, transmission electron microscopy (TEM), scanning electron
      microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy
      (XPS). Experimental results reveal different molecular packing modes in these
      aggregates, which in turn result in self-assembled nanostructures with different
      morphologies ranging from nanobelts for 1 through nanoribbons for 2 to cluster
      nanoflowers for 3. Intermolecular pi-pi and sulfur-sulfur interactions between
      metal-free phthalocyanine 1 lead to the formation of nanobelts. The additional Cu
      S coordination bond between the central copper ion of 2 and the sulfur atom of
      the adjacent molecule of 2 in cooperation with the intermolecular pi-pi stacking
      interaction increases the intermolecular interaction, and results in the
      formation of long nanoribbons for 2. In contrast to compounds 1 and 2, the
      special molecular structure of complex 3, together with the intermolecular pi-pi
      stacking interaction and additional Pb-S coordination bond, induces the formation
      of Pb-connected pseudo-double-deckers during the self-assembly process, which in
      turn further self-assemble into cluster nanoflowers. In addition, good
      semiconducting properties of the nanostructures fabricated from phthalocyanine
      derivatives 1-3 were also revealed by I-V measurements.

PMID- 22162356
TI  - Highly wrinkled cross-linked graphene oxide membranes for biological and charge
      storage applications.
AB  - Inspired by the amphiphilicity of graphene oxide (GO), the surface of water is
      used as a template for the assembly of a GO film. Methacrylate-functionalized GO
      sheets can be cross-linked instantaneously at the water-air interface to form a
      highly wrinkled membrane spreading over an extended area. The multiple covalent
      linkages amongst the GO sheets enhances the in-plane stiffness of the film
      compared to noncovalently bonded GO films. The highly convoluted GO membrane can
      be used in two applications: the promoting of spontaneous stem-cell
      differentiation towards bone cell lineage without any chemical inducers, and for
      supercapacitor electrodes. Due to reduced van der Waals restacking, capacitance
      values up to 211 F g(-1)  can be obtained. The scalable and inexpensive nature of
      this assembly route enables the engineering of membranes for applications in
      regenerative medicine and energy-storage devices where secondary structures like
      nanotopography and porosity are important performance enhancers.

PMID- 22162357
TI  - Epidemiology of humerus fractures in the United States: nationwide emergency
      department sample, 2008.
AB  - OBJECTIVE: To evaluate the occurrence of emergency department (ED) visits due to
      humerus fractures in the US. METHODS: We analyzed the 2008 Nationwide Emergency
      Department Sample, which contained approximately 28 million ED records. We
      identified the cases of interest using diagnostic codes for proximal, shaft, and
      distal humerus fractures. RESULTS: In 2008, approximately 370,000 ED visits in
      the US resulted from humerus fractures. Proximal humerus fractures were the most
      common, accounting for 50% of humerus fractures. The incidence rate of proximal
      humerus fractures followed the shape of an exponential function in the age groups
      40-84 years for women (R(2)  = 97.9%) and 60-89 years for men (R(2)  = 98.2%).
      After the exponential increase in these age intervals, the growth rate of
      proximal humerus fracture slowed and eventually decreased. The peak occurrence of
      distal humerus fractures was in children ages 5-9 years; however, elderly women
      had an increased risk. As the baby boomer generation ages, unless fracture
      prevention programs improve, more than 490,000 ED visits due to humerus fractures
      are expected in 2030 when the youngest of the baby boomers turn age 65 years.
      CONCLUSION: Compared to epidemiologic studies in Japan and European countries,
      the incidence rates of humerus fractures are substantially higher in the US. The
      high incidence rate of humerus fractures in the expanding elderly population may
      contribute to the recent trend of rapid increase in shoulder arthroplasty in the
      US. Rigorous safety measures to reduce falls and improved preventive treatments
      of osteoporosis are needed.

PMID- 22162359
TI  - The perceived personal control (PPC) questionnaire: reliability and validity in a
      sample from the United Kingdom.
AB  - Outcome measures are important assessment tools to evaluate clinical genetics
      services. Research suggests that perceived personal control (PPC) is an outcome
      valued by clinical genetics patients and clinicians. The PPC scale was developed
      in Hebrew to capture three dimensions of PPC: Cognitive, decisional, and
      behavioral control. This article reports on the first psychometric validation of
      the English translation of the PPC scale. Previous research has shown that the
      Hebrew and Dutch translations have good psychometric properties. However, the
      psychometric properties of the English translation have not been tested, and
      there is disagreement about the factor structure, with implications for how to
      score the measure. A total of 395 patients attending a clinical genetics
      appointment in the United Kingdom completed several measures at baseline, and a
      further 241 also completed measures at 2-4 weeks follow-up. The English language
      PPC has (a) a one-factor structure, (b) convergent validity with internal health
      locus of control (IHLC), satisfaction with life (SWL), depression, and
      authenticity, (c) high internal consistency (alpha = 0.83), and (d) sensitivity
      to change, being able to identify moderate changes in PPC following clinic
      attendance (Cohen's d = 0.40). These properties suggest the English language PPC
      measure is a useful tool for both clinical genetics research and for use as a
      Patient Reported Outcome Measure (PROM) in service evaluation.

PMID- 22162360
TI  - Face recognition performance of individuals with Asperger syndrome on the
      Cambridge Face Memory Test.
AB  - Although face recognition deficits in individuals with Autism Spectrum Disorder
      (ASD), including Asperger syndrome (AS), are widely acknowledged, the empirical
      evidence is mixed. This in part reflects the failure to use standardized and
      psychometrically sound tests. We contrasted standardized face recognition scores
      on the Cambridge Face Memory Test (CFMT) for 34 individuals with AS with those
      for 42, IQ-matched non-ASD individuals, and age-standardized scores from a large
      Australian cohort. We also examined the influence of IQ, autistic traits, and
      negative affect on face recognition performance. Overall, participants with AS
      performed significantly worse on the CFMT than the non-ASD participants and when
      evaluated against standardized test norms. However, while 24% of participants
      with AS presented with severe face recognition impairment (>2 SDs below the
      mean), many individuals performed at or above the typical level for their age:
      53% scored within +/- 1 SD of the mean and 9% demonstrated superior performance
      (>1 SD above the mean). Regression analysis provided no evidence that IQ,
      autistic traits, or negative affect significantly influenced face recognition:
      diagnostic group membership was the only significant predictor of face
      recognition performance. In sum, face recognition performance in ASD is on a
      continuum, but with average levels significantly below non-ASD levels of
      performance.

PMID- 22162364
TI  - Nickel- and cobalt-catalyzed direct alkylation of azoles with N-tosylhydrazones
      bearing unactivated alkyl groups.

PMID- 22162363
TI  - Elevated coding mutation rate during the reprogramming of human somatic cells
      into induced pluripotent stem cells.
AB  - Mutations in human induced pluripotent stem cells (iPSCs) pose a risk for their
      clinical use due to preferential reprogramming of mutated founder cell and
      selection of mutations during maintenance of iPSCs in cell culture. It is
      unknown, however, if mutations in iPSCs are due to stress associated with
      oncogene expression during reprogramming. We performed whole exome sequencing of
      human foreskin fibroblasts and their derived iPSCs at two different passages. We
      found that in vitro passaging contributed 7% to the iPSC coding point mutation
      load, and ultradeep amplicon sequencing revealed that 19% of the mutations
      preexist as rare mutations in the parental fibroblasts suggesting that the
      remaining 74% of the mutations were acquired during cellular reprogramming.
      Simulation suggests that the mutation intensity during reprogramming is ninefold
      higher than the background mutation rate in culture. Thus the factor induced
      reprogramming stress contributes to a significant proportion of the mutation load
      of iPSCs.

PMID- 22162365
TI  - Chemical synthesis of the englerins.
AB  - In the long lasting battle against cancer, Nature sometimes gives a helping hand
      to researchers to find new drugs for the treatment of diseases and improvement of
      patients' well-being. Englerin A has emerged as a promising anticancer candidate
      as well as being an exciting synthetic challenge for organic chemists. This focus
      review summarizes the total syntheses reported to date and the synthetic
      approaches toward analogues of this fascinating natural product.

PMID- 22162366
TI  - Chemically controlled bending of compositionally anisotropic microcylinders.

PMID- 22162368
TI  - Tip-enhanced near-field optical microscopy of quasi-1 D nanostructures.
AB  - High-resolution imaging and spectroscopy of single CdSe nanowires and carbon
      nanotubes using tip-enhanced near-field optical microscopy increases the optical
      excitation and emission rates within a nanoscale sample volume. The resulting
      signal enhancement for Raman scattering and photoluminescence as well as the tip
      sample-distance dependence are investigated.

PMID- 22162369
TI  - Incidence and risk factors for progressive multifocal leukoencephalopathy among
      patients with selected rheumatic diseases.
AB  - OBJECTIVE: To ascertain the incidence of progressive multifocal
      leukoencephalopathy (PML) in patients with selected rheumatic diseases, to
      describe the characteristics of PML cases occurring in this setting, and to
      evaluate the extent to which such cases occurred in the context of biologic
      therapies such as rituximab or tumor necrosis factor antagonists. METHODS: We
      conducted a large population-based study to describe the incidence and risk
      factors for PML among patients with rheumatoid arthritis, psoriatic arthritis,
      psoriasis, juvenile idiopathic arthritis, inflammatory bowel disease, and
      ankylosing spondylitis using national inpatient and outpatient administrative
      data from the entire Center for Medicare and Medicaid Services from 2000-2009.
      Suspected PML cases were identified using hospital discharge diagnosis codes.
      Risk factors for PML were evaluated using outpatient data >=6 months prior to PML
      diagnosis. RESULTS: Among 2,030,578 patients with autoimmune diseases of
      interest, a total of 53 PML cases were identified (2.6 per 100,000 patients).
      Most PML cases had human immunodeficiency virus (HIV) and/or cancer. Nine PML
      cases had evidence for biologic use prior to PML hospitalization, of which 3 had
      neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or
      6 months (all other biologics) prior to PML diagnosis. PML occurred at an
      estimated incidence of 0.2 per 100,000 patients with autoimmune diseases who did
      not have HIV or malignancy. CONCLUSION: PML occurs at a very low incidence among
      patients with rheumatic diseases but can occur even in the absence of HIV or
      malignancy.

PMID- 22162370
TI  - Incidence and nature of testicular toxicity findings in pharmaceutical
      development.
AB  - BACKGROUND: Testicular toxicity (TT) is a sporadic and challenging issue in
      pharmaceutical drug development. Efforts to develop TT screening assays or
      biomarkers have been overshadowed by consortium efforts to predict drug-induced
      toxicities such as hepatic injury, which are encountered more frequently.
      METHODS: To gauge the current state of the field and to prioritize future TT
      activities, the International Life Sciences Institute-Health and Environmental
      Sciences Institute Developmental and Reproductive Toxicology (DART) Technical
      Committee sponsored a survey to better understand the incidence and nature of TT
      findings encountered during drug development. RESULTS: Highlights from the 16
      survey respondents include: (1) Although preclinical TT was encountered
      relatively infrequently, half of the participants observed repeated problems with
      TT during pharmaceutical development, (2) despite control measures such as use of
      sexually mature animals to diminish confounding effects of spurious lesions,
      interpretation of TT remains a challenge, (3) "traditional" evaluation tools such
      as hormonal monitoring and newer approaches such as -omics are utilized to
      investigate testicular changes, and (4) an understanding of the risk and
      relevance of TT findings is achieved through joint consideration of factors such
      as species specificity, potential mode of action, and safety margins.
      CONCLUSIONS: TT remains a relatively uncommon but persistent challenge in
      pharmaceutical development. Although current preclinical TT approaches appear to
      be effective in limiting the occurrence of pharmaceutical candidate attrition in
      clinical trials, improved biomarker or screening platforms would allow companies
      to identify TT at an earlier stage, thus decreasing the time and resources
      expended on safety evaluation of pharmaceutical candidates.

PMID- 22162371
TI  - Flexible pillared graphene-paper electrodes for high-performance electrochemical
      supercapacitors.
AB  - Flexible graphene paper (GP) pillared by carbon black (CB) nanoparticles using a
      simple vacuum filtration method is developed as a high-performance electrode
      material for supercapacitors. Through the introduction of CB nanoparticles as
      spacers, the self-restacking of graphene sheets during the filtration process is
      mitigated to a great extent. The pillared GP-based supercapacitors exhibit
      excellent electrochemical performances and cyclic stabilities compared with GP
      without the addition of CB nanoparticles. At a scan rate of 10 mV s(-1) , the
      specific capacitance of the pillared GP is 138 F g(-1)  and 83.2 F g(-1)  with
      negligible 3.85% and 4.35% capacitance degradation after 2000 cycles in aqueous
      and organic electrolytes, respectively. At an extremely fast scan rate of 500 mV
      s (-1) , the specific capacitance can reach 80 F g(-1)  in aqueous electrolyte.
      No binder is needed for assembling the supercapacitor cells and the pillared GP
      itself may serve as a current collector due to its intrinsic high electrical
      conductivity. The pillared GP has great potential in the development of promising
      flexible and ultralight-weight supercapacitors for electrochemical energy
      storage.

PMID- 22162372
TI  - A comparison of the Ghent and revised Ghent nosologies for the diagnosis of
      Marfan syndrome in an adult Korean population.
AB  - Recently, a revised Ghent nosology has been established for the diagnosis of
      Marfan syndrome (MFS) that puts more weight on the aortic root aneurysm and
      ectopia lentis. We compared the application of the Ghent and revised Ghent
      nosologies in adult Korean patients for whom there is suspicion of MFS. From
      January 1995 to June 2010, we enrolled 106 patients older than 20 years for whom
      there was suspicion of MFS, and who had undergone genetic analysis of the
      fibrillin-1 gene (FBN1). Of 106 patients, 86 patients (81%) fulfilled the
      criteria of the Ghent nosology, and 84 patients (79%) met the criteria of the
      revised Ghent nosology. The two patients who met the Ghent nosology criteria, but
      not the criteria of the revised Ghent nosology were diagnosed with Loeys-Dietz
      syndrome and MASS phenotype. The level of agreement between both nosologies was
      very high (kappa = 0.94, 95% confidence interval: 0.86 to 1.0). Marfan-like
      syndromes were diagnosed in 30% (6/20 patients) with negative Ghent and revised
      Ghent criteria and no FBN1 mutations. These results suggest that adult Korean
      patients who fulfill the old Ghent criteria almost all fulfill the new criteria
      for the diagnosis of MFS.

PMID- 22162373
TI  - The inflammatory response in the pathogenesis of asthma.

PMID- 22162374
TI  - Lessons learned from the asthma clinical research network.

PMID- 22162375
TI  - How can I improve outcomes in asthma?

PMID- 22162376
TI  - Recent developments in asthma research, diagnosis, and treatment.

PMID- 22162377
TI  - Exercise-induced bronchoconstriction in the 21st century.

PMID- 22162378
TI  - Patient education. Avoiding asthma triggers: a primer for patients.

PMID- 22162379
TI  - Helping asthma patients.

PMID- 22162381
TI  - NICE's recommendations for thromboembolism are not evidence based.

PMID- 22162382
TI  - Anatomy of the bones of the foot.

PMID- 22162383
TI  - More secrets of the MMR scare. Who saw the "histological findings"?

PMID- 22162380
TI  - Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in
      human germ cells derived in vitro.
AB  - Our understanding of human germ cell development is limited in large part due to
      inaccessibility of early human development to molecular genetic analysis.
      Pluripotent human embryonic stem cells (hESCs) and induced pluripotent stem cells
      (iPSCs) have been shown to differentiate to cells of all three embryonic germ
      layers, as well as germ cells in vitro, and thus may provide a model for the
      study of the genetics and epigenetics of human germline. Here, we examined
      whether intrinsic germ cell translational, rather than transcriptional, factors
      might drive germline formation and/or differentiation from human pluripotent stem
      cells in vitro. We observed that, with overexpression of VASA (DDX4) and/or DAZL
      (Deleted in Azoospermia Like), both hESCs and iPSCs differentiated to primordial
      germ cells, and maturation and progression through meiosis was enhanced. These
      results demonstrate that evolutionarily unrelated and divergent RNA-binding
      proteins can promote meiotic progression of human-derived germ cells in vitro.
      These studies describe an in vitro model for exploring specifics of human
      meiosis, a process that is remarkably susceptible to errors that lead to
      different infertility-related diseases.

PMID- 22162384
TI  - Reading the riot acts.

PMID- 22162385
TI  - NICE needs reform.

PMID- 22162386
TI  - Why do you want to be a doctor?

PMID- 22162387
TI  - Audiovisual speech integration in autism spectrum disorders: ERP evidence for
      atypicalities in lexical-semantic processing.
AB  - In typically developing (TD) individuals, behavioral and event-related potential
      (ERP) studies suggest that audiovisual (AV) integration enables faster and more
      efficient processing of speech. However, little is known about AV speech
      processing in individuals with autism spectrum disorders (ASD). This study
      examined ERP responses to spoken words to elucidate the effects of visual speech
      (the lip movements accompanying a spoken word) on the range of auditory speech
      processing stages from sound onset detection to semantic integration. The study
      also included an AV condition, which paired spoken words with a dynamic scrambled
      face in order to highlight AV effects specific to visual speech. Fourteen
      adolescent boys with ASD (15-17 years old) and 14 age- and verbal IQ-matched TD
      boys participated. The ERP of the TD group showed a pattern and topography of AV
      interaction effects consistent with activity within the superior temporal plane,
      with two dissociable effects over frontocentral and centroparietal regions. The
      posterior effect (200-300 ms interval) was specifically sensitive to lip
      movements in TD boys, and no AV modulation was observed in this region for the
      ASD group. Moreover, the magnitude of the posterior AV effect to visual speech
      correlated inversely with ASD symptomatology. In addition, the ASD boys showed an
      unexpected effect (P2 time window) over the frontocentral region (pooled
      electrodes F3, Fz, F4, FC1, FC2, FC3, FC4), which was sensitive to scrambled face
      stimuli. These results suggest that the neural networks facilitating processing
      of spoken words by visual speech are altered in individuals with ASD.

PMID- 22162389
TI  - 2-D DIGE analysis of UV-C radiation-responsive proteins in globe artichoke
      leaves.
AB  - Plants respond to ultraviolet stress inducing a self-defence through the
      regulation of specific gene family members. The UV acclimation is the result of
      biochemical and physiological processes, such as enhancement of the antioxidant
      enzymatic system and accumulation of UV-absorbing phenolic compounds (e.g.
      flavonoids). Globe artichoke is an attractive species for studying the protein
      network involved in UV stress response, being characterized by remarkable levels
      of inducible antioxidants. Proteomic tools can assist the evaluation of the
      expression patterns of UV-responsive proteins and we applied the difference in
      gel electrophoresis (DIGE) technology for monitoring the globe artichoke proteome
      variation at four time points following an acute UV-C exposure. A total of 145 UV
      C-modulated proteins were observed and 119 were identified by LC-MS/MS using a
      ~144,000 customized Compositae protein database, which included about 19,000
      globe artichoke unigenes. Proteins were Gene Ontology (GO) categorized,
      visualized on their pathways and their behaviour was discussed. A predicted
      protein interaction network was produced and highly connected hub-like proteins
      were highlighted. Most of the proteins differentially modulated were chloroplast
      located, involved in photosynthesis, sugar metabolisms, protein folding and
      abiotic stress. The identification of UV-C-responsive proteins may contribute to
      shed light on the molecular mechanisms underlying plant responses to UV stress.

PMID- 22162390
TI  - Reaction of acetals with various carbon nucleophiles under non-acidic conditions:
      C-C bond formation via a pyridinium-type salt.
AB  - Mild substitution reactions of acetals with carbon nucleophiles via the
      pyridinium-type salts generated by the treatment of acetals with TESOTf-2,4,6
      collidine or 2,2'-bipyridyl have been developed. Various carbon nucleophiles,
      such as organocuprates, silyl enol ethers, enamines, etc., reacted with the
      pyridinium-type salts to give the corresponding substituted products in good
      yields. The reactions proceeded under very mild conditions (non-acidic
      conditions) and thus acid-sensitive functional groups can be tolerated during the
      reaction. In addition, only an acetal can form the pyridinium-type salt and react
      with nucleophiles in the presence of a ketal. This unusual selectivity is in
      contrast to general methods conducted under acidic conditions.

PMID- 22162391
TI  - Serial ionic exchange for the synthesis of multishelled copper sulfide hollow
      spheres.

PMID- 22162393
TI  - Airway manifestations in childhood granulomatosis with polyangiitis (Wegener's).
AB  - OBJECTIVE: Granulomatosis with polyangiitis (Wegener's) (GPA) is a necrotizing
      granulomatous vasculitis affecting the upper and lower respiratory tract,
      kidneys, and other small vessels throughout multiple organ systems. Recently,
      classification criteria for childhood GPA have been proposed and include the
      addition of airway stenosis. Airway inflammation occurs more frequently in
      children than adults and often proves difficult to diagnose and treat. Our
      objectives were to 1) determine the frequency of airway involvement in a cohort
      of children with GPA as defined by the European League Against
      Rheumatism/Paediatric Rheumatology International Trials Organisation/Pediatric
      Rheumatology European Society (EULAR/PRINTO/PRES) criteria, 2) document the
      frequency of specific airway findings, and 3) review our treatment approach to
      children with GPA-related airway disease. METHODS: A retrospective chart review
      was performed on patients ages <18 years with a diagnosis of vasculitis evaluated
      at the Cleveland Clinic between 2004 and 2010. RESULTS: Twenty-eight patients
      fulfilling the EULAR/PRINTO/PRES classification criteria for the diagnosis of
      childhood GPA were included in the analysis. There was a mean followup time of
      3.1 years. The overall prevalence of any airway disease was 86%, with upper
      airway involvement in 86% and laryngotracheobronchial (LTB) disease in 50% of
      patients. LTB disease was present at diagnosis in 36%, while in the remaining 14%
      it developed on immunosuppressive therapy. Ten patients underwent a successful
      endoscopic intervention. CONCLUSION: Airway manifestations frequently occur in
      childhood GPA. Inflammatory changes can occur at any point in the disease course,
      necessitating diligent surveillance. Endoscopic interventions for LTB stenotic
      lesions represent a safe and effective therapeutic option.

PMID- 22162395
TI  - A DFT study of the interaction between microhydrated anions and
      naphthalendiimides.
AB  - The characteristics of the interaction of anions with naphthalendiimides, the
      basic structural motif of a newly synthesized anion channel based on anion...pi
      interactions, are studied by computational methods. Stable complexes are formed
      with bromide, chloride, fluoride or hydroxide anions, which exhibit strong
      anion...pi interactions in the gas phase. Following the sequence of the
      polarizing power of the anions, hydroxide and fluoride complexes are the most
      strongly interacting. The presence of a small number of water molecules strongly
      affects the anion...pi interactions, especially for hydroxide and fluoride
      complexes, so the differences in interaction strength among the anions drop
      significantly. The calculations suggest that a small number of water molecules
      can be crucial to reducing dehydration cost and contributing to stabilizing
      interactions with the naphthalendiimide units.

PMID- 22162396
TI  - RNA-binding protein L1TD1 interacts with LIN28 via RNA and is required for human
      embryonic stem cell self-renewal and cancer cell proliferation.
AB  - Human embryonic stem cells (hESC) have a unique capacity to self-renew and
      differentiate into all the cell types found in human body. Although the
      transcriptional regulators of pluripotency are well studied, the role of
      cytoplasmic regulators is still poorly characterized. Here, we report a new stem
      cell-specific RNA-binding protein L1TD1 (ECAT11, FLJ10884) required for hESC self
      renewal and cancer cell proliferation. Depletion of L1TD1 results in immediate
      downregulation of OCT4 and NANOG. Furthermore, we demonstrate that OCT4, SOX2,
      and NANOG all bind to the promoter of L1TD1. Moreover, L1TD1 is highly expressed
      in seminomas, and depletion of L1TD1 in these cancer cells influences self
      renewal and proliferation. We show that L1TD1 colocalizes and interacts with
      LIN28 via RNA and directly with RNA helicase A (RHA). LIN28 has been reported to
      regulate translation of OCT4 in complex with RHA. Thus, we hypothesize that L1TD1
      is part of the L1TD1-RHA-LIN28 complex that could influence levels of OCT4. Our
      results strongly suggest that L1TD1 has an important role in the regulation of
      stemness.

PMID- 22162398
TI  - Alcohol consumption and binge drinking in young adult childhood cancer survivors.
AB  - BACKGROUND: This study compared frequency of alcohol consumption and binge
      drinking between young adult childhood cancer survivors and the general
      population in Switzerland, and assessed its socio-demographic and clinical
      determinants. PROCEDURE: Childhood cancer survivors aged <16 years when diagnosed
      1976-2003, who had survived >5 years and were currently aged 20-40 years received
      a postal questionnaire. Reported frequency of alcohol use and of binge drinking
      were compared to the Swiss Health Survey, a representative general population
      survey. Determinants of frequent alcohol consumption and binge drinking were
      assessed in a multivariable logistic regression. RESULTS: Of 1,697 eligible
      survivors, 1,447 could be contacted and 1,049 (73%) responded. Survivors reported
      more often than controls to consume alcohol frequently (OR = 1.7; 95%CI = 1.3
      2.1) and to engage in binge drinking (OR = 2.9; 95%CI = 2.3-3.8). Peak frequency
      of binge drinking in males occurred at age 24-26 years in survivors, compared to
      age 18-20 in the general population. Socio-demographic factors (male gender, high
      educational attainment, French and Italian speaking, and migration background
      from Northern European countries) were most strongly associated with alcohol
      consumption patterns among both survivors and controls. CONCLUSIONS: The high
      frequency of alcohol consumption found in this study is a matter of concern. Our
      data suggest that survivors should be better informed on the health effects of
      alcohol consumption during routine follow-up, and that such counseling should be
      included in clinical guidelines. Future research should study motives of alcohol
      consumption among survivors to allow development of targeted health interventions
      for this vulnerable group.

PMID- 22162397
TI  - Designer hydrophilic regions regulate droplet shape for controlled surface
      patterning and 3D microgel synthesis.
AB  - A simple technique is presented for controlling the shapes of micro- and
      nanodrops by patterning surfaces with special hydrophilic regions surrounded by
      hydrophobic boundaries. Finite element method simulations link the shape of the
      hydrophilic regions to that of the droplets. Shaped droplets are used to
      controllably pattern planar surfaces and microwell arrays with microparticles and
      cells at the micro- and macroscales. Droplets containing suspended sedimenting
      particles, initially at uniform concentration, deposit more particles under
      deeper regions than under shallow regions. The resulting surface concentration is
      thus proportional to the local fluid depth and agrees well with the measured and
      simulated droplet profiles. A second application is also highlighted in which
      shaped droplets of prepolymer solution are crosslinked to synthesize microgels
      with tailored 3D geometry.

PMID- 22162399
TI  - Mycosis fungoides following pityriasis lichenoides: an exceptional event or a
      potential evolution?

PMID- 22162400
TI  - Successful management of extreme hypertriglyceridemia in a child with acute
      lymphoblastic leukemia by temporarily omitting dexamethasone while continuing
      asparaginase.

PMID- 22162401
TI  - Evaluation of conserved and ultra-conserved non-genic sequences in chromosome
      15q15-linked periodic catatonia.
AB  - Conserved and ultra-conserved non-genic sequence elements (CNGs, UCEs) between
      human and other mammalian genomes seem to constitute a heterogeneous group of
      functional sequences which likely have important biological function. To
      determine whether variation in CNGs and UCEs contributes to risk for the
      schizophrenic subphenotype of periodic catatonia (according to K. Leonhard; OMIM
      605419), we evaluated non-coding elements at a critical 7.35 Mb interval on
      chromosome 15q15 in 8 unrelated cases with periodic catatonia (derived from
      pedigrees compatible with linkage to chromosome 15q15) and 8 controls, followed
      by association studies in a cohort of 510 cases and controls. Among 65 CNGs
      (>=100 bp, 100% identity; human-mouse comparison), 7 CNGs matched criteria for
      UCE (>=200  bp, 100% identity). A hot spot of 62/65 CNGs (95%) appeared at the
      MEIS2 locus, which implicates functional importance of associated (ultra
      )conserved elements to this early developmental gene, which is present in the
      human fetal neocortex and associated with metabolic side effects to antipsychotic
      drugs. Further CNGs were identified at the PLCB2 and DLL4 locus or located
      intergenic between TYRO3 and MAPKBP1. Automated sequencing revealed genetic
      variation in 12.3% of CNGs, but frequencies were low (MAF: 0.06-0.4) in cases.
      Three variants located inside CNGs/UCEs were found in cases only. In a case
      control association study we could not confirm a significant association of these
      three CNG-variants with periodic catatonia. Our results suggest genetic variation
      in (ultra-)conserved non-genic sequence elements which might alter functional
      properties. The identified variants are genetically not associated with the
      phenotype of periodic catatonia.

PMID- 22162402
TI  - Autism in adults.

PMID- 22162403
TI  - Proteomics reveals selective regulation of proteins in response to memory-related
      serotonin stimulation in Aplysia californica ganglia.
AB  - The marine mollusk Aplysia californica (Aplysia) is a powerful model for learning
      and memory due to its minimalistic nervous system. Key proteins, identified to be
      regulated by the neurotransmitter serotonin in Aplysia, have been successfully
      translated to mammalian models of learning and memory. Based upon a recently
      published large-scale analysis of Aplysia proteomic data, the current study
      investigated the regulation of protein levels 24 and 48 h after treatment with
      serotonin in Aplysia ganglia using a 2-D gel electrophoresis approach. Protein
      spots were quantified and protein-level changes of selected proteins were
      verified by Western blotting. Among those were Rab GDP dissociation inhibitor
      alpha (RabGDIalpha), synaptotagmin-1 and deleted in azoospermia-associated
      protein (DAZAP-1) in cerebral ganglia, calreticulin, RabGDIalpha, DAZAP-1,
      heterogeneous nuclear ribonucleoprotein F (hnRNPF), RACK-1 and actin
      depolymerizing factor (ADF) in pleural ganglia and DAZAP-1, hnRNPF and ADF in
      pedal ganglia. Protein identity of the majority of spots was confirmed by a gel
      based mass spectrometrical method (FT-MS). Taken together, protein-level changes
      induced by the learning-related neurotransmitter serotonin in Aplysia ganglia are
      described and a role for the abovementioned proteins in synaptic plasticity is
      proposed.

PMID- 22162405
TI  - Heterogeneous fenton catalysts based on activated carbon and related materials.
AB  - The Fenton reaction is widely used for remediation of waste water and for the
      degradation of organic pollutants in water. Currently, there is considerable
      interest to convert the classical Fenton reaction, which consumes stoichiometric
      amounts of iron(II) salts, into a catalytic process that is promoted by a solid.
      This review describes the work that has used carbonaceous materials either
      directly as catalysts or, more frequently, as a large-area support for
      catalytically activated transition metals or metal-oxide nanoparticles. The
      interest in this type of catalyst derives from the wide use of carbon in
      conventional water treatments and the wide applicability of the Fenton reaction.
      After two general sections that illustrate the scope and background of Fenton
      chemistry, the review describes the activity of activated carbon in the absence
      or presence of metal-containing particles. The last sections of the review focus
      on different types of carbonaceous materials, such as carbon nanotubes and
      diamond nanoparticles. The review concludes with a section that anticipates
      future developments in this area, which are aimed at overcoming the current
      limitations of low activity and occurrence of metal leaching.

PMID- 22162406
TI  - Sonochemical synthesis of 0D, 1D, and 2D zinc oxide nanostructures in ionic
      liquids and their photocatalytic activity.
AB  - Ultrasound synthesis of zinc oxide from zinc acetate and sodium hydroxide in
      ionic liquids (ILs) is a fast, facile, and effective, yet highly morphology- and
      size-selective route to zinc oxide nanostructures of various dimensionalities. No
      additional organic solvents, water, surfactants, or templating agents are
      required. Depending on the synthetic conditions, the selective manufacturing of
      0D, 1D, and 2D ZnO nanostructures is possible: Whereas the formation of rodlike
      structures is typically favored, ZnO nanoparticles can be obtained either under
      strongly basic conditions or by use of ILs with a long alkyl chain, such as 1-n
      alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C(n)mim][Tf(2)N];
      n>8). A short ultrasound irradiation time favors the formation of ZnO nanosheets.
      Prolonged irradiation leads to the conversion of the ZnO nanosheets into
      nanorods. In contrast, ionothermal synthesis (conventional heating) does not
      allow for morphology tuning by variation of the IL or other synthesis conditions,
      as the longer reaction times required lead always to the formation of well
      developed hexagonal nanocrystals with prismatic tips. The ZnO nanostructures
      synthesized by using ultrasound were efficient photocatalysts in the
      photodegradation of methyl orange. The photoactivity was observed to be as high
      as 95 % for ZnO nanoparticles obtained in [C(10)mim][Tf(2)N].

PMID- 22162407
TI  - A versatile protocol for the quantitative and smooth conversion of phosphane
      oxides into synthetically useful pyrazolylphosphonium salts.
AB  - A convenient protocol for the smooth conversion of the resistant P-O bond in
      phosphane oxides into a reactive P-N bond of synthetically useful
      pyrazolylphosphonium salts is described. A highly charged, oxophilic, phosphorus
      centered trication is employed and the reactions are conducted at room
      temperature with quantitative yields. The resulting pyrazolylphosphonium cations
      are valuable synthetic intermediates and are used for the synthesis of a variety
      of organophosphorus compounds. This represents a new approach towards the
      transformation of the rather inert phosphoryl group under very mild reaction and
      workup conditions and aims towards alternatives to existing reduction methods for
      phosphane oxide functionalization.

PMID- 22162409
TI  - Transcatheter closure of the perimembranous ventricular septal defect-preclinical
      trial of a new Amplatzer device.
AB  - OBJECTIVES: This study assessed the feasibility and efficacy of implanting a new
      nitinol device for closure of perimembranous ventricular septal defects in a
      swine model. BACKGROUND: Perimembranous ventricular septal defect occurs in 80%
      of patients requiring treatment for congenital heart disease. METHODS: The
      Amplatzer perimembranous ventricular septal occluder device (pmVSO2 device, AGA
      Medical Company, Plymouth MN) is a new transcatheter Nitinol device containing
      polyester fabric designed to close the perimembranous ventricular septal defect
      (VSD). The device has 75% reduction in radial force, 45% reduction in clamping
      force, and increased stability as compared to the previous version. The device
      was implanted in six swine with naturally occurring perimembranous VSD with
      immediate, 1, 7, ~30, and ~90 day followup by echocardiography, angiography, and
      final pathological examination. RESULTS: The device was successfully implanted in
      all animals and was retrievable and repositionable. There was complete occlusion
      of the VSD in five of six cases without embolization. There was no thrombus
      formation on the device or occurrence of complete heart block. A single instance
      of a tiny residual shunt was attributed to capture of tricuspid valve apparatus.
      CONCLUSIONS: The success of this animal study confirms safety and feasibility of
      the Amplatzer pmVSO2 device. Human trials are planned.

PMID- 22162410
TI  - A supramolecular protecting group strategy introduced to the organic solid state:
      enhanced reactivity through molecular pedal motion.

PMID- 22162411
TI  - Bleeding complications in primary percutaneous coronary intervention of ST
      elevation myocardial infarction in a radial center.
AB  - OBJECTIVES: We evaluated the incidence, types, and prognostic impact of bleeding
      complications in a non-selected patient population with ongoing STEMI treated
      with aggressive antithrombotic treatment and routine radial primary PCI.
      BACKGROUND: Bleeding complications remain frequent and deleterious in primary PCI
      through femoral approach. METHODS: STEMI patients (n = 671) were evaluated for
      bleeding complications using a web-based registry (e-PARIS). In-hospital bleeding
      was adjudicated using the TIMI definition. RESULTS: In this non-selected, high
      risk population, 6.1% had cardiogenic shock on admission, 3.9% out-of-hospital
      cardiac arrest. Radial access (88%) was the default strategy as was abciximab
      (78%). Clopidogrel loading dose ranged from 300 to 900 mg. Pre-hospital
      fibrinolysis was rare (7.1%). Hemodynamic support devices (IABP, ECMO, Tandem
      Heart) were needed in 7.0%. In-hospital TIMI Major and TIMI Major/minor bleedings
      occurred in 2.5 and 5.7% of the population, respectively. In-hospital and 1-year
      mortality rates were 5.5 and 8.2%, respectively. Patients with in-hospital TIMI
      Major/minor bleeding had a higher 1-year mortality rate (31.6% vs. 3.8%, P <
      0.001). The most frequent bleeding site was gastro-intestinal. Radial access was
      a strong predictor of survival (OR 0.33; 95%CI 0.17-0.56; P = 0.002).
      CONCLUSIONS: In the setting of radial primary PCI, the rates and types of
      bleeding complications are somewhat different from those observed with femoral
      primary PCI. The gastro-intestinal tract has become the most frequent site of
      bleeding after radial primary PCI. The use of radial access appears independently
      associated with survival.

PMID- 22162412
TI  - Diameter-dependent thermal transport in individual ZnO nanowires and its
      correlation with surface coating and defects.
AB  - A systematic study of the thermal transport properties of individual single
      crystal zinc oxide (ZnO) nanowires (NWs) with diameters in the range of ~50-210
      nm is presented. The thermal conductivity of the NWs is found to be dramatically
      reduced by at least an order of magnitude compared to bulk values, due to
      enhanced phonon-boundary scattering with a reduction in sample size. While the
      conventional phonon transport model can qualitatively explain the temperature
      dependence, it fails to account for the diameter dependence. An empirical
      relationship for assessing diameter-dependent thermal properties is observed,
      which shows an approximately linear dependence of the thermal conductivity on the
      cross-sectional area of the NWs in the measured diameter range. Furthermore, it
      is found that an amorphous-carbon layer coating on the NWs does not perturb the
      thermal properties of the NW cores, whereas 30 keV Ga(+) ion irradiation at low
      dose (~4 * 10(14) cm(-2)) leads to a remarkable reduction of the thermal
      conductivity of the ZnO NWs.

PMID- 22162413
TI  - Short gold nanorod growth revisited: the critical role of the bromide counterion.
AB  - A one-step, surfactant-assisted, seed-mediated method has been utilized for the
      growth of short gold nanorods with reasonable yield by modifying an established
      synthesis protocol. Among the various parameters that influence nanorod growth,
      the impact of the bromide counterion has been closely scrutinized. During this
      study it has been shown that, irrespective of its origin, the bromide counterion
      [cetyltrimethylammonium bromide (CTAB) or NaBr] plays a crucial role in the
      formation of nanorods in the sense that there is a critical [Br(-)]/[Au(3+)]
      ratio (around 200) to achieve nanorods with a maximum aspect ratio. Beyond this
      value, bromide can be considered as a poisoning agent unless shorter nanorods are
      required. The use of AgNO(3) helps in symmetry breaking for gold nanorod growth,
      whereas the bromide counterion controls the growth kinetics by selective
      adsorption on the facets of the growth direction. Thus, a proper balance between
      bromide ions and gold cations is also one of the necessary parameters for
      controlling the size of the gold nanorods; this has been discussed thoroughly.
      The results have been discussed based on their absorption spectra and finally
      shape evolution has been confirmed by TEM. Due to their efficient absorption in
      the near-IR region, these short nanorods were used in photothermal imaging of
      living COS-7 cells with improved signal-to-background ratios.

PMID- 22162414
TI  - Validity of brief screening tools for cognitive impairment in rheumatoid
      arthritis and systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the validity of standardized screening assessments of
      cognitive functioning to detect neuropsychological impairment evaluated using a
      comprehensive battery in systemic lupus erythematosus (SLE) and rheumatoid
      arthritis (RA). METHODS: This is a cross-sectional study using a combined cohort
      of 139 persons with SLE and 82 persons with RA. Screening cut points were
      empirically derived using receiver operating characteristic curves and threshold
      selection methods. Screening measures included the Hopkins Verbal Learning Test
      Revised (HVLT-R) learning and delayed recall indices and phonemic fluency, a
      composite measure of the 3 cognitive screening tests, and the Perceived Deficits
      Questionnaire-Short Form (PDQ-SF), a self-report measure of cognitive symptoms. A
      comprehensive neuropsychological battery was administered as the "gold standard"
      index of neuropsychological impairment. RESULTS: Rates of neuropsychological
      impairment were 27% and 15% for the SLE and RA cohorts, respectively. Optimal
      threshold estimations were derived for 5 screening techniques. The HVLT-R
      learning and phonemic fluency indices yielded the greatest sensitivity at 81%.
      The PDQ-SF yielded the lowest sensitivity at 52%. All measures were significantly
      associated with neuropsychological impairment after controlling for relevant
      sociodemographic covariates and depression. CONCLUSION: These results suggest
      that telephone-administered screening techniques may be useful measures to
      identify persons with neuropsychological impairment. Specifically, measures of
      phonemic fluency and verbal learning appeared to be most sensitive and least
      likely to misclassify impaired individuals as cognitively intact. Self-reported
      questionnaires may have relatively decreased sensitivity compared to standardized
      interviewer-administered cognitive measures.

PMID- 22162415
TI  - Nanobiotechnology for the capture and manipulation of circulating tumor cells.
AB  - A necessary step in metastasis is the dissemination of malignant cells into the
      bloodstream, where cancer cells travel throughout the body as circulating tumor
      cells (CTC) in search of an opportunity to seed a secondary tumor. CTC represent
      a valuable diagnostic tool: evidence indicates that the quantity of CTC in the
      blood has been shown to relate to the severity of the illness, and samples are
      readily obtained through routine blood draws. As such, there has been a push
      toward developing technologies to reliably detect CTC using a variety of
      molecular and immunocytochemical techniques. In addition to their use in
      diagnostics, CTC detection systems that isolate CTC in such a way that the cells
      remain viable will allow for the performance of live-cell assays to facilitate
      the development of personalized cancer therapies. Moreover, techniques for the
      direct manipulation of CTC in circulation have been developed, intending to block
      metastasis in situ. We review a number of current and emerging micro- and
      nanobiotechnology approaches for the detection, capture, and manipulation of rare
      CTC aimed at advancing cancer treatment.

PMID- 22162416
TI  - Characterization of the human primary visual cortex and cerebellum proteomes
      using shotgun mass spectrometry-data-independent analyses.
AB  - We present the first characterization of the human occipital lobe (primary visual
      cortex) and cerebellum proteomes. Proteins were identified using a combination of
      gel electrophoresis and data-independent nanoflow liquid chromatography mass
      spectrometry (nLC-MS(E) ). The resulting data sets comprised 391 and 330 unique
      proteins in occipital lobe and cerebellum, respectively, present in at least 75%
      of the analyzed samples with 297 proteins found in common. These proteins have
      been associated previously with conditions, such as neurological disorder,
      progressive motor neuropathy, Parkinson's disease and schizophrenia. The unique
      proteins identified in the occipital lobe included the interesting finding of
      growth hormone and several members of the Ca2+-dependent calmodulin kinase and
      serine/threonine protein phosphatase families. The complete mapping of these and
      other brain proteomes may help in the elucidation of neurological processes and
      identify potential targets for therapeutic strategies.

PMID- 22162418
TI  - Energy from plants and microorganisms: progress in plant-microbial fuel cells.
AB  - Plant-microbial fuel cells (PMFCs) are newly emerging devices, in which
      electricity can be generated by microorganisms that use root exudates as fuel.
      This review presents the development of PMFCs, with a summary of their power
      generation, configurations, plant types, anode and cathode materials, biofilm
      communities, potential applications, and future directions.

PMID- 22162417
TI  - SNP variants within the vanilloid TRPV1 and TRPV3 receptor genes are associated
      with migraine in the Spanish population.
AB  - The transient receptor potential (TRP) superfamily of non-selective cationic
      channels are involved in several processes plausibly relevant to migraine
      pathophysiology, including multimodal sensory and pain perception, central and
      peripheral sensitization, and regulation of calcium homeostasis. With the aim of
      identifying single nucleotide polymorphisms (SNPs) in TRP genes that may confer
      increased genetic susceptibility to migraine, we carried out a case-control
      genetic association study with replication, including a total of 1,040 cases and
      1,037 controls. We genotyped 149 SNPs covering 14 TRP genes with known brain
      expression. The two-stage study comprised samples of 555 and 485 Spanish,
      Caucasian patients, selected according to the ICHD-II criteria for the diagnosis
      of migraine without aura (MO) or migraine with aura (MA). In the discovery
      sample, 19 SNPs in ten TRP genes showed nominal association (P < 0.05) with MO,
      MA, or overall migraine. In the replication sample, nominal association was
      confirmed for TRPV3 rs7217270 in MA and TRPV1 rs222741 in the overall migraine
      group. Risk haplotypes were identified for seven of the genes showing nominal
      association in the discovery set, but none of them was replicated. The present
      findings suggest that members of the vanilloid TRPV subfamily of receptors
      contribute to the genetic susceptibility to migraine in the Spanish population.

PMID- 22162419
TI  - A 45-year-old man with flank pain and inability to ejaculate.

PMID- 22162421
TI  - The effects of biological environments on the electron-relay functionality of
      tryptophan residues in proteins.
AB  - Clarifying the contribution of tryptophan (Trp) to electron-transfer (ET)
      processes in different protein surroundings can help to understand the effective
      pathway of ET in proteins. Interactions between Trp residues and protein
      microsurroundings involve intermolecular H-bonds, cation and pi-electron clouds
      of aromatic rings, the secondary structure and pi orbital of aromatic rings, and
      so on. Detailed analyses reveal that the microsurroundings play an important role
      in modulating the electron-relay function of Trp in proteins. Generally,
      microsurroundings with strong Lewis acidity inhibit electron hole transport
      through Trp residues. Systems with weak Lewis acidity finely tune the electron
      relay ability of Trp in proteins, while those with strong Lewis basicity strongly
      enhance the electron-relay ability of Trp residues.

PMID- 22162422
TI  - Circularly polarized lanthanide luminescence from Langmuir-Blodgett films formed
      from optically active and amphiphilic Eu(III)-based self-assembly complexes.

PMID- 22162423
TI  - Ulcerative colitis as a progressive disease: the forgotten evidence.
AB  - In the management of Crohn's disease, earlier aggressive treatment is becoming
      accepted as a strategy to prevent or retard progression to irreversible bowel
      damage. It is not yet clear, however, if this same concept should be applied to
      ulcerative colitis. Hence, we review herein the long-term structural and
      functional consequences of this latter disease. Disease progression in ulcerative
      colitis takes six principal forms: proximal extension, stricturing,
      pseudopolyposis, dysmotility, anorectal dysfunction, and impaired permeability.
      The precise incidence of these complications and the ability of earlier, more
      aggressive treatment to prevent them have yet to be determined.

PMID- 22162424
TI  - Preliminary experience with personalized and targeted therapy for pediatric brain
      tumors.
AB  - BACKGROUND: A new generation of anticancer drugs has reached clinical care in
      common diseases, but their use in rare diseases such as pediatric brain tumors
      lags behind since conventional clinical trial design requires larger patient
      numbers. PROCEDURE: We designed individualized treatment protocols for pediatric
      patients with relapsed brain tumors, based upon the patient's treatment history.
      In addition, each tumor was analyzed with morphoproteomics using a panel of
      markers to show treatment targets, resulting in a list of potential novel drugs
      to be added to chemotherapy. Here, we present the concept and report the
      experiences of the first patients enrolled in the program. RESULTS: Eleven
      treatment protocols were designed using morphoproteomic information and given to
      eight patients. The histological diagnoses included: medulloblastoma (n = 3),
      glioblastoma multiforme (n = 2), atypical teratoid rhabdoid tumor (n = 1),
      choroid plexus carcinoma (n = 1), and primitive neuroectodermal tumors (n = 1).
      Tumor markers included p-ERK, Topoisomerase IIa, Bcl-2, VEGF-A, p-STAT3, ER-beta,
      p-mTOR, and p-NF-kappaBp65. The novel agents included sorafenib, bevacizumab,
      fulvestrant, rapamycin, bortezomib, and curcumin. The response to the first
      protocol was complete response: 1, partial response: 1, stable disease: 0,
      progressive disease: 4, and continuous complete remission: 2. The median Event
      Free Survival was 0.32 year +/- 0.4. For the comparison with the institutional
      control group, the individual response probability was calculated. The observed
      response was superior to the historical controls (P = 0.006 Whitman U-test).
      CONCLUSION: This approach warrants further, systematic evaluation as proof of
      concept and then expansion to drug-specific hypotheses.

PMID- 22162425
TI  - Nanowired drug delivery for neuroprotection in central nervous system injuries:
      modulation by environmental temperature, intoxication of nanoparticles, and
      comorbidity factors.
AB  - Recent developments in nanomedicine resulted in targeted drug delivery of active
      compounds into the central nervous system (CNS) either through encapsulated
      material or attached to nanowires. Nanodrug delivery by any means is supposed to
      enhance neuroprotection due to rapid accumulation of drugs within the target area
      and a slow metabolism of the compound. These two factors enhance neuroprotection
      than the conventions drug delivery. However, this is still uncertain whether
      nanodrug delivery could alter the pharmacokinetics of compounds making it more
      effective or just longer exposure of the compound for extended period of time is
      primarily responsible for enhanced effects of the drugs. Our laboratory is
      engaged in understanding of the nanodrug delivery using TiO(2) nanowires in CNS
      injuries models, for example, spinal cord injury (SCI), hyperthermia and/or
      intoxication of nanoparticles with or without other comorbidity factors, that is,
      diabetes or hypertension in rat models. Our observations suggest that nanowired
      drug delivery is effective under normal situation of SCI and hyperthermia as
      evidenced by significant reduction in the blood-brain barrier (BBB) breakdown,
      brain edema formation, cognitive disturbances, neuronal damages, and brain
      pathologies. However, when the pathophysiology of these CNS injuries is
      aggravated by nanoparticles intoxication or comorbidity factors, adjustment in
      dosage of nanodrug delivery is needed. This indicates that further research in
      nanomedicine is needed to explore suitable strategies in achieving greater
      neuroprotection in CNS injury in combination with nanoparticles intoxication or
      other comorbidity factors for better clinical practices.

PMID- 22162429
TI  - Study of a possible role of the monoamine oxidase A (MAOA) gene in paranoid
      schizophrenia among a Chinese population.
AB  - Monoamine oxidase A (MAOA) is the enzyme responsible for degradation of several
      monoamines, such as dopamine and serotonin that are considered as being two of
      the most important neurotransmitters involved in the pathophysiology of
      schizophrenia. To study a possible role of the MAOA gene in conferring
      susceptibility to schizophrenia, the present study genotyped the variable number
      of tandem repeat (VNTR) polymorphism and 41 SNPs across this gene among 555
      unrelated patients with paranoid schizophrenia and 567 unrelated healthy
      controls. Quantitative real-time PCR analysis was employed to quantify expression
      of MAOA mRNA in 73 drug-free patients. While none of these genotyped DNA markers
      showed allelic association with paranoid schizophrenia, haplotypic association
      was found for the VNTR-rs6323, VNTR-rs1137070, and VNTR-rs6323-rs1137070
      haplotypes in female subjects. Nevertheless, no significant change of the
      expression of MAOA mRNA was detected in either female or male patients with
      paranoid schizophrenia. Our study suggests that the interaction between genetic
      variants within the MAOA gene may contribute to an increased risk of paranoid
      schizophrenia, but the precise mechanism needs further investigation.

PMID- 22162430
TI  - Transitioning to the radial artery as the preferred access site for cardiac
      catheterization: an academic medical center experience.
AB  - OBJECTIVES: To evaluate procedural and safety metrics of transradial (TR) versus
      transfemoral (TF) cardiac catheterization (CATH) and percutaneous coronary
      interventions (PCI) during a complete institutional transition from TF to TR as
      the preferred access. BACKGROUND: The TR approach has been shown to reduce
      complications compared to TF for CATH and PCI, but concerns of longer procedure
      times have limited utilization in the United States. METHODS: 4,172 consecutive
      CATH and PCI procedures were performed (2,665 TF; 1,507 TR) at Wake Forest
      Baptist Medical Center from January 2009 to November 2010. We assessed in
      hospital procedural and safety metrics. RESULTS: After 6 months of a preferred TR
      strategy, TR to TF crossover rate was 9.1%, and 65% of all cases were TR
      procedures. For the cath lab (all TF + TR), we observed small but significant
      increases in procedural metrics for Preferred TR (last third) compared to
      Preferred TF (first third). This appeared to be due to increased access times,
      procedure length, fluoroscopy times, and contrast use for TR versus TF
      (propensity score matched). Nonetheless, over the course of the study, there was
      a trend for a decrease in all procedural metrics with TR use. Access site
      complications (2.3% TF, 1.2% TR) and bleeding (2.5% TF, 2.1% TR), both P < 0.05,
      decreased over the course of the study. CONCLUSIONS: Our observations support the
      concept that complete transition of a cath lab to a preferred TR strategy is
      feasible, achieves lower rates of vascular and bleeding complications but with
      modest increases in overall procedural metrics.

PMID- 22162431
TI  - Separation of reaction product and palladium catalyst after a Heck coupling
      reaction by means of organic solvent nanofiltration.
AB  - Organic solvent nanofiltration (OSN) is a recently commercialized technology,
      which we have used to develop a method for the separation of a target product and
      the Pd catalyst from a Heck coupling postreaction mixture. The experimental setup
      included commercially available polyimide copolymer membranes with molecular
      weight cut-off (MWCO) values in the range of 150-300 Da, acetone as the solvent,
      and a working pressure (N(2)) of 3 MPa. The investigation of the membranes
      revealed that a membrane with a MWCO of 200 Da provided quantitative retention of
      the Pd catalyst and quantitative recovery of the target product by means of a
      cross-flow dia-nanofiltration procedure.

PMID- 22162432
TI  - A rapid analytical method for the detection of plasma volume expanders and
      mannitol based on the urinary saccharides and polyalcohols profile.
AB  - A screening procedure specifically developed for the detection of saccharides and
      polyalcohols in human urine in the framework of doping control analysis is
      presented. The proposed method, set-up, and validated to detect the abuse of
      dextran, hydroxyethyl starch and mannitol as a doping practice in sport, involves
      only one enzymatic hydrolysis step and the direct injection into a liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) system. The chromatographic
      conditions were optimized to allow the efficient separation of compounds with the
      same molecular weight. Good linearity (R(2) 0.990-0.995) and reproducibility of
      relative retention times (CV% lower than 1) and of relative abundances of
      characteristic ion transitions (CV% lower than 10) were obtained. The lower
      limits of detection and quantification were in the range of 30-100 ug/ml. Since
      the analytes studied are present also in non-doping products (e.g. in fruit as
      well as in food products and drugs additives), the developed method was also used
      to establish a range of reference urinary concentrations: 600 doping control
      samples and 30 samples from volunteers not using any medication were considered.
      While the hydrolysis products (isomaltose and maltose hydroxyl-ethylated), used
      as specific markers for the detection of dextran and hydroxyethyl starch abuse,
      were not detected in urine; mannitol was present in all urines in a concentration
      range of 30-1200 ug/ml. Since no criteria of positivity for mannitol has been
      established yet, the results obtained in this study could be considered, in
      combination with those of previous researches, as a starting point to fix a
      threshold value for doping control purpose.

PMID- 22162433
TI  - Outcomes in patients with systemic lupus erythematosus with and without a
      prolonged serologically active clinically quiescent period.
AB  - OBJECTIVE: Serologically active clinically quiescent (SACQ) systemic lupus
      erythematosus (SLE) patients' discordance presents a clinical dilemma. Does
      active serology alone warrant treatment? We explore outcomes in patients with and
      without a prolonged SACQ period, comparing the rate of damage accrual by Systemic
      Lupus International Collaborating Clinics/American College of Rheumatology Damage
      Index (SDI) and incidences of renal damage and coronary artery disease (CAD) over
      a decade. METHODS: SACQ was defined as a >=2-year sustained period without
      clinical activity, with persistent serologic activity (increased anti-double
      stranded DNA and/or hypocomplementemia). Antimalarials were permissible and
      corticosteroids/immunosuppressives were not. The SACQ patients were matched for
      relevant variables with SLE controls. Change in the SDI and incidences of CAD and
      renal damage were compared. Descriptive statistics were used; comparisons were
      made using t-tests and McNemar's tests. RESULTS: Fifty-five SACQ patients and 110
      controls were identified. The mean +/- SD SDI score at 3 years from the start of
      the SACQ period was 0.70 +/- 1.27 in the SACQ patients versus 1.13 +/- 1.54 in
      controls (P < 0.0001), and by 10 years was 1.26 +/- 1.68 versus 2.26 +/- 2.23 (P
      = 0.001); the intergroup difference in damage significantly increased over 10
      years. Initially, 2 (3.6%) of the SACQ patients had CAD versus 7 (6.4%) of the
      controls (P = 0.32), with 1 (1.8%) new case in SACQ patients versus 8 (7.3%) new
      cases in controls over 10 years (P = 0.06). Baseline serum creatinine level did
      not differ between the groups. By definition, the SACQ patients had no baseline
      proteinuria versus 13 (12.3%) of the controls (P < 0.0001). By year 10, 2 (3.6%)
      SACQ patients versus 26 (23.6%) controls had renal damage (P < 0.0001).
      CONCLUSION: Patients with a prolonged SACQ period accrued less damage over a
      decade compared to matched controls, supporting management with active
      surveillance without treatment during an SACQ period.

PMID- 22162434
TI  - Controlled assemblies of gold nanorods in PVA nanofiber matrix as flexible free
      standing SERS substrates by electrospinning.
AB  - Under control: Controlled assemblies of gold nanorods in a poly(vinyl alcohol)
      (PVA) nanofiber matrix with tunable optical properties can be achieved by using
      electrospinning. The resultant assemblies can be used as substrates for surface
      enhanced Raman spectroscopy (SERS). This work provides a facile way to control
      alignment of anisotropic nanostructures in a polymer nanofiber matrix and
      generates new assemblies with interesting properties.

PMID- 22162435
TI  - Desmoplastic small round cell tumors with EWS-WT1 fusion transcript in children
      and young adults.
AB  - BACKGROUND: The presence of the EWS-WT1 gene fusion transcript (GFT) is
      characteristic of desmoplastic small round cell tumor (DSRCT), a rare and very
      aggressive disease for which the treatment has not yet been clearly standardized.
      METHODS: This was a retrospective national multicenter analysis of young patients
      <30 years with tumors expressing the EWS-WT1-GFT, designed to determine whether
      extensive surgery had an impact on survival. RESULTS: Between 1995 and 2006, a
      EWS-WT1-GFT was detected in the tumors of 38 patients, 17 (44.7%) of whom had had
      a different initial pathologic diagnosis prior to molecular testing. Mean age was
      13.2 years (range: 4-29.7 years). Only 9 patients (24%) had localized disease.
      Treatment was heterogeneous. Nine patients had "limited" surgical resections and
      22 underwent "extensive" surgery. Two-year event-free survival and overall
      survival were 14.4% and 50%, respectively. Among the five patients who were alive
      in complete remission, four had undergone extensive and complete surgery.
      CONCLUSIONS: Detection of the EWS-WT1-GFT plays a major role in the diagnosis of
      DSRCT. No survival difference was observed according to extent of surgery, but
      complete surgery seemed to offer the best chance of long-term survival. High-dose
      chemotherapy or local radiotherapy did not appear to improve survival in this
      retrospective analysis, but larger prospective studies are needed to provide
      definitive conclusions on the role of these treatments.

PMID- 22162436
TI  - Photocrosslinked co-networks from glycidylmethacrylated gelatin and poly(ethylene
      glycol) methacrylates.
AB  - Biopolymer-based systems with adjustable macroscopic properties that can be
      varied in a wide range using only small changes in chemical composition are
      promising candidates for biomaterial-induced autoregeneration.
      Glycidylmethacrylated gelatin is photopolymerized with the addition of PEG mono-
      or dimethacrylate to form co-networks in pH = 7.4 PBS. The degree of swelling (Q)
      and water uptake (H) in PBS at 37  degrees C are tailorable for PEGDMA co
      networks (Q ~ 250-650 vol%), while the storage modulus of swollen networks at 3 
      degrees C can be adjusted by the PEG(D)MA content (G' = 0.7-145 kPa). Indirect
      cytotoxicity tests on ethylene oxide sterilized films show non-toxic responses
      for the homonetwork and all but one PEGDMA-containing co-networks materials.

PMID- 22162438
TI  - Solid-supported gallium triflate: an efficient catalyst for the three-component
      ketonic Strecker reaction.
AB  - In light of the growing interest in the use of rare earth metal triflates as
      water-tolerant Lewis acid catalysts, we embarked upon the development of a solid
      supported gallium triflate (PS-Ga(OTf)(2) ) derivative as a means of increasing
      the cleanliness and cost effectiveness of using these increasingly expensive
      catalytic materials in synthetic processes. Having previously highlighted the
      advantages associated with coupling solid-supported catalysis and the emerging
      area of micro-reaction technology, we screened PS-Ga(OTf)(2)  for activity
      towards the ketonic Strecker reaction, in which the target alpha-aminonitriles
      were obtained in higher yield and purity compared to reactions reported in
      literature, in which the analogous homogeneous catalyst was used.

PMID- 22162437
TI  - Genetic and environmental contributions to self-reported thoughts of self-harm
      and suicide.
AB  - Thoughts of self-harm and suicidal behavior are thought to be influenced by both
      genetics and environment. Molecular genetic studies are beginning to address the
      question of which genes may be involved and whether different genes may be
      expressed in men and women. We examined thoughts of self-harm and suicidal
      behavior in a large general population twin sample including male and female same
      and opposite-sex twins. In this study, data on self-reported thoughts of self
      harm and suicide were obtained from self-report questionnaires (Beck Depression
      Inventory and Youth or Adult Self Report forms) in 6,265 twin pairs (11,008
      individuals) aged 11-90 (62% female) from the Netherlands Twin Registry.
      Liability threshold models were compared including sex and age (linear and
      quadratic) effects. Models were compared using measures of parsimony to calculate
      the simplest model to the data. A model with additive genetic and unique
      environmental contributions fitted the data for both males and females. There
      were no qualitative sex differences, but the relative contributions differed
      between men and women. Heritability was higher in women (0.74, 95% CI 0.65-0.81)
      than men (0.45, 95% CI 0.28-0.61). The remaining variance was accounted for by
      environmental influence unique to an individual. These results suggest
      contributions from additive genetic factors to self-reported thoughts of self
      harm and suicide and support the continued study of both molecular genetic and
      individual-specific environmental risk factors.

PMID- 22162439
TI  - Inflammation: what role in pediatric cancer?
AB  - There is growing evidence for the importance of chronic inflammation in the
      pathogenesis of adult cancers and for an ongoing role of the inflammatory
      response in tumor growth and metastasis. Here, we examine how these processes
      relate to pediatric malignancies. While it is unlikely that chronic inflammation
      plays a significant role in driving malignant progression in childhood tumors
      that typically have developmental origins, the inflammatory response does appear
      to play an important role in the development and progression of many types of
      childhood cancer. An enhanced understanding of these processes will be of
      critical importance in developing novel therapeutic strategies.

PMID- 22162440
TI  - Development of a polar lipid profiling method by supercritical fluid
      chromatography/mass spectrometry.
AB  - We established a high-throughput and high-resolution analytical method based on
      supercritical fluid chromatography (SFC) coupled with mass spectrometry (MS) for
      the simultaneous profiling of diverse polar lipids in a mixture. Trimethylsilyl
      (TMS) derivatization was used for the analysis of ten polar lipids:
      phosphatidylglycerol (PG), phosphatidic acid (PA), phosphatidylinositol (PI),
      lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE),
      lysophosphatidylglycerol (LPG), lysophosphatidic acid (LPA),
      lysophosphatidylinositol (LPI), sphingomyeline (SM), and sphingosine-1-phosphate
      (S1P). Using the developed method, the peak tailings of PA, PI, LPA, LPI, and S1P
      improved, and the limit of detection of PG, PI, LPA, LPI, and S1P was enhanced by
      12-, 40-, 510-, 39-, and 1490-fold, respectively. Next, in the analysis of sheep
      plasma, 20 minor species of PI, LPC, LPE, and SM, and 7 molecular species of LPA,
      LPI, and S1P were additionally analyzed. The relative ratio of the molecular
      species in each polar lipid was also found by quantification. Finally, the
      simultaneous and detail profiling of ten polar lipids was successfully performed
      by SFC/MS applying TMS derivatization. This developed method is particularly
      applicable to metabolomics, especially for targeting polar lipids.

PMID- 22162441
TI  - Design of online solid phase extraction-liquid chromatography-tandem mass
      spectrometry (SPE-LC-MS/MS) hyphenated systems for quantitative analysis of small
      organic compounds in biological matrices.
AB  - Three online solid phase extraction-liquid chromatography-tandem mass
      spectrometry (SPE-LC-MS/MS) method examples are presented where two different
      types of chromatographic columns or solvent systems were coupled to meet specific
      analytical objectives: (i) SPE of target analytes by restricted access media from
      high ionic strength urine matrix was coupled with reversed phase LC-MS/MS
      conditions accommodating high ionization potentials of the analytes (urinary
      bisphenol A and other phenolic derivatives); (ii) strong cation exchange SPE of
      analytes of diverse polarity and pK(a)  was coupled with reversed phase LC-MS/MS
      analysis (urinary atrazine metabolites); (iii) pre-concentration of low pg per
      sample analytes by weak anion exchange SPE was hyphenated with ion pair LC-MS
      analysis (intracellular nucleotide triphosphate analogs). With these examples we
      suggest a conductive generic work flow for the development of online SPE-LC-MS
      methods and show how advanced commercial LC devices and software allow for the
      design of complex yet highly versatile analytical separation systems suited to
      the unique physicochemical properties of the target analytes.

PMID- 22162442
TI  - Metabolite analysis revisited.

PMID- 22162444
TI  - Closing one of the last gaps in polyionene compositions: alkyloxyethylammonium
      ionenes as fast-acting biocides.
AB  - Alkyloxyethylammonium ionenes are reported as biocompatible biocides with a time
      of biocidal action within a few minutes. The presence of both ethoxyethyl and
      aliphatic spacers besides long alkyl chain substituents on the quaternary
      nitrogen atom differentiates these biocides structurally from the known
      polyionenes. The influence of alkyl spacer length, counter ion and length of the
      pendant alkyl groups on the antibacterial properties is studied. E. coli is
      adopted as a test organism. MIC and MBC values are determined via broth dilution
      methods; time-dependent tests are accomplished by determining the number of
      viable cells with the spread-plate method after different contact times.
      Structural characterization is conducted via NMR and mass spectrometry
      techniques.

PMID- 22162445
TI  - An optical platform for cell tracking in adult zebrafish.
AB  - Adult zebrafish are being increasingly used as a model in cancer and stem cell
      research. Here we describe an integrated optical system that combines a laser
      scanning confocal microscope (LSCM) and an in vivo flow cytometer (IVFC) for
      simultaneous visualization and cell quantification. The system is set up
      specifically for non-invasive tracking of both stationary and circulating cells
      in adult zebrafish (casper) that have been engineered to be optically
      transparent. Confocal imaging in this instrument serves the dual purpose of
      visualizing fish tissue microstructure and an imaging-based guide to locate a
      suitable vessel for quantitative analysis of circulating cells by IVFC. We
      demonstrate initial testing of this novel instrument by imaging the transparent
      adult zebrafish casper vasculature and tracking circulating cells in CD41
      GFP/Gata1-DsRed transgenic fish whose thrombocytes/erythrocytes express the green
      and red fluorescent proteins. In vivo measurements allow cells to be tracked
      under physiological conditions in the same fish over time, without drawing blood
      samples or sacrificing animals. We also discuss the potential applications of
      this instrument in biomedical research.

PMID- 22162446
TI  - Synthesis of renewable bisphenols from creosol.
AB  - A series of renewable bisphenols has been synthesized from creosol (2-methoxy-4
      methylphenol) through stoichiometric condensation with short-chain aldehydes.
      Creosol can be readily produced from lignin, potentially allowing for the large
      scale synthesis of bisphenol A replacements from abundant waste biomass. The
      renewable bisphenols were isolated in good yields and purities without resorting
      to solvent-intense purification methods. Zinc acetate was shown to be a selective
      catalyst for the ortho-coupling of formaldehyde, but was unreactive when more
      sterically demanding aldehydes were used. Dilute HCl and HBr solutions were shown
      to be effective catalysts for the selective coupling of aldehydes in the position
      meta to the hydroxyl group. The acid solutions could be recycled and reused
      multiple times without decrease in activity or yield.

PMID- 22162447
TI  - Endobronchial echinococcosis presenting as non-resolving pneumonia.
AB  - Hydatid disease of the lungs is caused by larval cysts of the Echinococcus
      tapeworm. Pulmonary cysts may occasionally invade bronchi or pleura as a result
      of coughing, trauma, or elevated intra-abdominal pressure. We present the case of
      a patient evaluated for non-resolving pneumonia whose radiographic and
      bronchoscopic findings were strikingly similar to those seen in pulmonary
      tuberculosis with endobronchial invasion; he was ultimately diagnosed with
      pulmonary echinococcosis. This case underscores the importance of considering
      unusual diagnoses even when typical features of more common conditions are
      present.

PMID- 22162448
TI  - Improvement of photoluminescence of Cu+ ion in Li2SO4.
AB  - The synthesis of the Li(2)SO(4) : Cu phosphor using a wet chemical method is
      reported here. The XRD technique showed the crystalline nature of the prepared
      material. The presence of Na and K in the host affected the observed
      photoluminescence characteristics of Li(2) SO(4) : Cu. Photoluminescent emission
      spectra of Li(2)SO(4) : Cu phosphor showed a very strong prominet peak at 387 nm
      in the indigo region due to 3d(9) 4 s(1) <-> 3d(10) transition of the Cu(+) ion.
      The increase in peak intensity of the PL spectrum suggests that Cu(+) acts as the
      luminescence center in the present matrix.

PMID- 22162449
TI  - Mechanoluminescence properties of gamma-ray-irradiated BaSO4:Eu phosphors.
AB  - BaSO(4) activated with various concentrations of Eu were prepared by solid-state
      reaction technique. Thermoluminescence (TL) and mechanoluminescence (ML) of gamma
      ray-irradiated BaSO(4):Eu(2)O(3) phosphors were recorded. In the TL glow curve of
      the phosphor a single peak at 170 degrees C was observed. The TL of the phosphors
      were also recorded after deforming the phosphors by dropping a piston of mass 0.4
      kg onto them with different impact velocities. TL intensity (after deformation)
      decreased with increasing the impact velocity. In the ML intensity vs time curve
      two peaks were observed. ML intensity increased with increasing impact velocity
      of the piston and the time corresponding to peak ML intensity shifted to a
      shorter time value. ML intensity decreased drastically when it was recorded after
      annealing the sample at 170 degrees C. The BaSO(4) phosphors activated with 0.1
      mol% of Eu(2)O(3) showed optimum TL and ML. The photoluminescence emission
      spectrum of the sample showed that Eu enters as Eu(2+) ion in host lattice.

PMID- 22162450
TI  - Chemical and photophysical mechanism of fluorescence enhancement of 3
      quinolineboronic acid upon change of pH and binding with carbohydrates.
AB  - The free 3-quinolineboronic acid (3-QBA) with the lowest (n-pi*) excited singlet
      is non- or weakly fluorescent while protonated 3-QBA has the lowest (pi-pi*)
      excited singlet state and is highly fluorescent. The hybridization of boronic
      atom or charge transfer from aromatic ring to boronic acid group plays a
      secondary role in affecting fluorescence intensity. Binding with carbohydrate at
      a proper acidity, the hybridization of boron atom changes from sp(2) to sp(3) and
      the nitrogen atom in the quinoline ring is partially protonated, resulting in
      large enhancement of fluorescence. Meanwhile, the fluorescent lifetime of 3-QBA
      produces obvious change by binding with carbohydrates. Quinoline boronic acid is
      an important water-soluble fluorescence sensor for carbohydrate recognition. Both
      the remarkable changes in intensity and lifetime of 3-QBA can act as working
      parameters in recognition of carbohydrates at physiological pH.

PMID- 22162451
TI  - A new and sensitive catalytic resonance scattering spectral assay for the
      detection of laccase using guaiacol as substrate.
AB  - In pH 4.0 succinic acid-sodium hydroxide buffer solution, laccase catalyzed the
      oxidization of guaiacol substrate to form red particles, which exhibited a strong
      resonance scattering (RS) peak at 590 nm. Under the chosen conditions, as the
      laccase increased, the RS intensity (DeltaI) increased linearly. The DeltaI was
      proportional to laccase activity in the range of 0.10-1.2 U/mL, with a regression
      equation of DeltaI = 734.0 U(laccase) - 9.7, and a detection limit of 0.05 U/mL.
      This RS method was applied to the detection of laccase activity in real samples,
      and the results were agreement with those from spectrophotometry.

PMID- 22162452
TI  - Synthesis and characterization of a novel high luminescent gold-2-mercapto-1
      methyl-imidazole complex.
AB  - Synthesis and characterization of a new gold-2-mercapto-1-methyl imidazole are
      reported. This new organic material shows an extraordinary fluorescence activity
      (superfluorescence) up to 220 degrees C with an unusual quantum yield of 0.2.
      Both fluorescence and NMR spectroscopy were applied to understand the behavior of
      the gold-2-mercapto-1-methylimidazole complex. Results suggest that the
      superfluorescence activity can be attributed to the shrinking of the HOMO-LUMO
      band gap energy following complexation of the organic imidazole system with gold.

PMID- 22162453
TI  - A novel spectrofluorimetric method for the assay of pseudoephedrine hydrochloride
      in pharmaceutical formulations via derivatization with 4-chloro-7
      nitrobenzofurazan.
AB  - A new highly sensitive and specific spectrofluorimetric method has been developed
      to determine a sympathomimetic drug pseudoephedrine hydrochloride. The present
      method was based on derivatization with 4-chloro-7-nitrobenzofurazan in phosphate
      buffer at pH 7.8 to produce a highly fluorescent product which was measured at
      532 nm (excitation at 475 nm). Under the optimized conditions a linear
      relationship and good correlation was found between the fluorescence intensity
      and pseudoephedrine hydrochloride concentration in the range of 0.5-5 ug mL(-1).
      The proposed method was successfully applied to the assay of pseudoephedrine
      hydrochloride in commercial pharmaceutical formulations with good accuracy and
      precision and without interferences from common additives. Statistical comparison
      of the results with a well-established method showed excellent agreement and
      proved that there was no significant difference in the accuracy and precision.
      The stoichiometry of the reaction was determined and the reaction pathway was
      postulated.

PMID- 22162454
TI  - Effect of bis-triazoles on a ribose-based fluorescent sensor.
AB  - We synthesized two ribosyl-based fluorescent sensors. Both sensors have an
      anthracene as the fluorophore, but they differ in the recognition site for metal
      ions. One (3) has two ribosyl esters, and the other (6) has two triazole groups
      linked to two ribosyl esters. Among the metal ions examined in MeOH, compound 3
      displayed a large chelation-enhanced fluorescence (CHEF) effect with Hg(2+) and
      Cu(2+) ions, and compound 6 displayed a large chelation-quenched fluorescence
      (CHQF) effect with Cu(2+) and Ni(2+) ions. The results demonstrated that the
      absence (sensor 3) and presence (sensor 6) of an incorporated bis-triazole group
      in a ribosyl-based fluorescent sensor conferred different preferences and
      distinct binding modes for metal ions.

PMID- 22162455
TI  - A highly selective fluorescent sensor for mercury ion (II) based on azathia-crown
      ether possessing a dansyl moiety.
AB  - An intramolecular charge transfer (ICT) fluorescent sensor 1 using a dansyl
      moiety as the fluorophore and an azathia-crown ether as the receptor was
      designed, synthesized and characterized. The ions-selective signaling behaviors
      of the sensor 1 were investigated in CH(3) CN-H(2) O (1:1, v/v) by fluorescence
      spectroscopy. It exhibited remarkable fluorescence quenching upon addition of
      Hg(2+), which was attributed to the 1:1 complex formation between 1 and Hg(2+),
      while other selected metal ions induced basically no spectral changes. The sensor
      1 showed a rapid and linear response towards Hg(2+) in the concentration range
      from 5.0 * 10(-7) to 1.0 * 10(-5) mol L(-1) with the detection limit of 1.0 * 10(
      7) mol L(-1). Furthermore, the whole process could be carried out in a wide pH
      range of 2.0-8.0 and was not disturbed by other metal ions. Thus, the sensor 1
      was used for practical determination of Hg(2+) in different water samples with
      satisfactory results.

PMID- 22162456
TI  - Cathodic electrochemiluminescent behavior of luminol at nafion-nano-TiO2 modified
      glassy carbon electrode.
AB  - The electrochemiluminescence (ECL) behavior of luminol on a nafion-nano-TiO(2)
      modified glassy carbon electrode (nafion-nano-TiO(2)--GCE) was studied. Two ECL
      peaks (ECL-1 and ECL-2) were found during cathodic potential scanning. ECL-1 at
      ca -0.4 V (vs Ag--AgCl reference electrode) came from the reaction between
      luminol and active oxygen anion produced at the GCE surface directly, while ECL-2
      at ca -0.9 V (vs Ag--AgCl reference electrode) came from the reaction between
      luminol and the active oxygen anion catalyzed by TiO(2.) The possible mechanism
      for the generation of both ECL peaks has been proposed. The reproducibility of
      the ECL intensities on nafion-nano-TiO(2)--GCE at ECL-1 and ECL-2 was good, with
      relative standard deviations (n = 10) of 4.3 and 1.3%, respectively. The ECL-2
      generated at the nafion-nano-TiO(2)--GCE surface was further developed to detect
      the dissolved oxygen, and a detection limit of 0.02 mg/L was achieved. The
      proposed method was applied to detect dissolved oxygen in water with satisfactory
      result.

PMID- 22162457
TI  - Flow injection chemiluminescence determination of vitamin B12 using on-line UV
      persulfate photooxidation and charge coupled device detection.
AB  - A sensitive chemiluminescence method for vitamin B(12) using a charge-coupled
      device (CCD) photodetector combined with on-line UV-persulfate oxidation in a
      simple continuous flow system has been developed. The principle for the
      determination of vitamin B(12) is based on the enhancive effect of cobalt (II) on
      the chemiluminescence reaction between luminol and percarbonate in alkaline
      medium. In addition, percarbonate has been investigated and proposed as a
      powerful source of hydrogen peroxide as oxidant agent in this chemiluminescence
      reaction. The digestion of vitamin B(12) to release the cobalt (II) is reached by
      UV irradiation treatment in a persulfate medium. The CCD detector, directly
      connected to the flow cell, is used with the continuous flow manifold to obtain
      the full spectral characteristics of cobalt (II) catalyzed luminol-percarbonate
      reaction. The vitamin B(12) oxidation process and chemical conditions for the
      chemiluminescence reaction were investigated and optimized. The increment of the
      emission intensity was proportional to the concentration of vitamin B(12) ,
      giving a second-order calibration graph over the cobalt (II) concentration range
      from 10 to 5000 MUg L(-1)(r(2) = 0.9985) with a detection limit of 9.3 MUg L(-1).
      The proposed method was applied to the determination of vitamin B(12) in
      different kinds of pharmaceuticals.

PMID- 22162458
TI  - Bioluminescent enzyme assay for the indication of plant stress in enclosed life
      support systems.
AB  - The application of bioluminescent sensors for monitoring key metabolites and
      enzymes that are indicators of stress in plants is demonstrated. The sensitivity
      of bioluminescent assay for NAD(P)H and NAD(P)(+) was about 0.5 and 1 nmol,
      respectively. The levels of NAD(P)H and NAD(P)(+) in radish (Raphanus sativus)
      root extracts from controls and from stress-induced conditions were compared. To
      induce environmental stress, the plants were grown in enclosed environmental
      chambers with low pressure (9 or 32 kPa), high humidity (>80%) and low oxygen
      partial pressure (down to 3.3-6.5 kPa). The concentrations of NAD(P)(+) and
      NAD(P)H in plants varied under stress conditions. Decreasing both total pressure
      from 101.5 to 32 or 9 kPa and partial pressure of oxygen increased the ratio of
      NAD(P)(+) /NAD(P)H from 0.2 to 4 or 6, respectively. The increase in this ratio
      suggests that plants are undergoing stress in these hypobaric environments. The
      developed bioluminescent assay for quantification of pyridine nucleotides in
      plant tissues is rapid, low-cost and easily performed.

PMID- 22162459
TI  - Luminescence studies of decomposition of ceric sulfate.
AB  - Literature results on the decomposition products of ceric sulfate are
      inconsistent. A group of researchers claim that ceric sulfate decomposed to ceric
      oxide without going through a cerous phase at any stage, while the results of the
      other group show that cerous sulfate is formed as an intermediate phase. Most of
      these studies used DTA/TGA, XRD and IR techniques. Cerous compounds can also be
      detected by the characteristic luminescence of Ce(3+). Using such techniques we
      show that the thermal decomposition of both monoclinic and betaCe(SO(4) )(2) .
      4H(2) O in air at 500 degrees C leads to the formation of cerous sulphate. Use of
      various atmospheres (air/N(2) /vacuum) and temperature profiles for the
      decomposition by the different researchers may be responsible for the
      discrepancies between literature results.

PMID- 22162460
TI  - Safety of central venous catheter placement at diagnosis of acute lymphoblastic
      leukemia in children.
AB  - BACKGROUND: Central venous catheters (CVC) facilitate the management of patients
      with cancer. Optimal timing for placement of a CVC is controversial. We sought to
      determine whether early placement in children with acute lymphoblastic leukemia
      (ALL), a group at high risk for infection and thrombosis, was associated with an
      increased rate of surgical complications. PROCEDURE: We evaluated the incidence
      and risk factors for early surgical complications in children with ALL diagnosed
      between 2004 and 2009 at a single pediatric cancer center. RESULTS: One hundred
      seventy-two patients were studied. There were 17 episodes of bloodstream
      infection, for a 30-day incidence of 9.8% (95% CI, 5.9-15%). There were no
      surgical site infections and no CVC was removed due to infection. Early
      thrombosis occurred in only one patient, 3 days after CVC placement. Infection
      was not influenced by catheter type, patient age, body mass index, or fever at
      the time of placement. The infection rate was not statistically higher when the
      ANC was <500/mm(3) at the time of CVC placement (14.2% vs. 6.8%; P = 0.12).
      CONCLUSION: Early CVC placement at the time of diagnosis of ALL was associated
      with a low surgical complication rate with no catheters requiring removal due to
      infection. Utilizing our current methods of preoperative preparation, surgical
      management and postoperative CVC care, early placement of a CVC is safe in
      children with ALL even when their ANC is <500/mm(3) , but larger cohort studies
      would be helpful to further clarify this issue.

PMID- 22162461
TI  - Use of capillary electrophoresis with chemiluminescence detection for sensitive
      determination of homocysteine.
AB  - A sensitive capillary electrophoresis (CE) method with chemiluminescence (CL)
      detection was developed for the determination of homocysteine (HCys) in human
      plasma. In this work, N-(4-aminobutyl)-N-ethylisoluminol was used as tagging
      reagent to label the analyte for achieving high assay sensitivity. N-(4
      Aminobutyl)-N-ethylisoluminol-tagged HCys after CE separation reacted with
      hydrogen peroxide in the presence of horseradish peroxidase, producing CL
      emission. Experimental conditions for labeling analyte, CE separation, and CL
      detection were studied. The CL intensity was proportional to the concentration of
      HCys in the range of 2.5*10(-8) to 5.0*10(-6) M. Detection limit (S/N=3) was
      7.6*10(-9) M. Human plasma samples from healthy donors were analyzed by the
      presented method. HCys levels were found to be in the range of 9.50-15.3 MUM. 

PMID- 22162463
TI  - Normalizing eating behavior reduces body weight and improves gastrointestinal
      hormonal secretion in obese adolescents.
AB  - HYPOTHESIS: Retraining obese adolescents to eat more slowly will lead to
      beneficial changes in circulating concentrations of gastrointestinal satiety
      hormones. METHODS: Ghrelin and peptide tyrosine-tyrosine were measured during an
      oral glucose tolerance test, at baseline and at 12 months during a randomized
      trial assessing the clinical effectiveness of a device (Mandometer) designed to
      retrain eating behavior. This computerized scale provided real-time feedback
      during meals in the intervention arm (n = 14) to slow down the speed of eating.
      The control group (n = 13) received only standard care aimed at improving
      lifestyle behavior. The Mandometer elicited greater improvements in weight loss
      than standard care. RESULTS: Compared with baseline, only those using the
      Mandometer exhibited lower mean levels of fasting ghrelin (48.14 +/- 18.47 vs.
      68.45 +/- 17.78 pg/ml; P = 0.002) and mean ghrelin area under the curve (72.08 +/
      24.11 vs. 125.50 +/- 29.72 pg/ml * min; P < 0.001) at 12 months. Absolute mean
      suppression in ghrelin at 60 min was enhanced (-40.50 +/- 21.06 vs. -12.14 +/-
      19.74 pg/ml * min; P = 0.001). Peptide tyrosine-tyrosine response at 90 min
      remained unaltered in the standard care arm, whereas those in the Mandometer arm
      increased (P < 0.001): the mean 90-min response increased by 72 pg/ml [95%
      confidence interval (CI) 52-92 pg/ml] between baseline and 12 months. In a
      partial correlation analysis adjusting for change (Delta) in body mass index sd
      scores, Delta meal duration correlated negatively with Delta absolute suppression
      in ghrelin at 60 min (r = -0.58; P = 0.037; 95% CI -0.79 to -0.27) and Delta
      ghrelin area under the curve (r = -0.62; P = 0.025; 95% CI -0.81 to -0.31).
      CONCLUSIONS: Retraining obese adolescents to eat more slowly has a significant
      impact on the gastrointestinal hormone response to a carbohydrate load,
      suggesting that externally modifiable eating behaviors actually regulate the
      hormonal response to food.

PMID- 22162462
TI  - MicroRNA therapeutics in cardiovascular medicine.
AB  - Cardiovascular diseases are the most common causes of human morbidity and
      mortality despite significant therapeutic improvements by surgical,
      interventional and pharmacological approaches in the last decade. MicroRNAs
      (miRNAs) are important and powerful mediators in a wide range of diseases and
      thus emerged as interesting new drug targets. An array of animal and even human
      miRNA-based therapeutic studies has been performed, which validate miRNAs as
      being successfully targetable to treat a wide range of diseases. Here, the
      current knowledge about miRNAs therapeutics in cardiovascular diseases on their
      way to clinical use are reviewed and discussed.

PMID- 22162464
TI  - Plasma bile acids are associated with energy expenditure and thyroid function in
      humans.
AB  - BACKGROUND/AIMS: Animal studies implicate a role of bile acids (BA) in thyroid
      regulated energy expenditure (EE) via activation of the TGR-5/adenylate
      cyclase/deiodinase type 2 pathway. Here we investigated these possible
      associations in humans. METHODS: EE, BA, and thyroid hormone status were assessed
      in 10 healthy subjects and eight patients with liver cirrhosis at baseline and
      after oral nutrition. In cirrhosis, blood was additionally sampled from the
      mesenteric vein and the radial artery. RESULTS: At baseline, BA and EE related
      positively (r = 0.648, P = 0.048 in healthy subjects; r = 0.833, P = 0.010 in
      cirrhosis; r = 0.556, P =0.017 in all), with the highest correlation with
      deoxycholic acid levels. The respiratory quotient associated negatively to
      baseline BA (all, r = -0.639, P = 0.004). Postprandially, serum TSH decreased in
      both groups (P < 0.05 each). In cirrhosis, the decrease of TSH after 60 min
      correlated to the meal-stimulated BA increase (r = -0.762, P = 0.028). To assess
      the mechanism involved, we studied a single human TSHoma and TalphaT1 mouse
      thyrotrope cells. In TSHoma cells, TGR-5 was predominantly expressed
      cytoplasmically, and in vitro stimulation with BA did not substantially alter
      cAMP or deiodinase type 2. CONCLUSIONS: Our data support a role of BA in human
      energy metabolism and in thyroid hormone control. Even though no convincing
      response to BA was demonstrated in TSHoma and TalphaT1 cells, the TSH decrease
      after a nutritional challenge suggests an interaction of BA on the set point of
      the thyroid axis.

PMID- 22162465
TI  - Loss of enteroendocrine cells in autoimmune-polyendocrine-candidiasis-ectodermal
      dystrophy (APECED) syndrome with gastrointestinal dysfunction.
AB  - BACKGROUND: Enteroendocrine (EE) cells are necessary for the regulation of
      gastrointestinal function. The lack of intestinal enteroendocrine cells in
      enteroendocrine cell dysgenesis causes severe malabsorptive diarrhea. Autoimmune
      polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is often accompanied
      by gastrointestinal (GI) symptoms. AIMS: We hypothesized that an autoimmune
      attack against the cells of the GI-associated diffuse endocrine system may be a
      specific feature of GI dysfunction in APECED disorders. METHODS: Biopsies were
      obtained during routine diagnostic endoscopy from 35 pediatric patients with
      gastrointestinal symptoms as well as from five healthy controls; biopsies were
      immunostained for chromogranin A and serotonin. Four patients were classified as
      APECED syndrome on molecular and clinical grounds. RESULTS: Immunohistological
      analysis of biopsies along the GI tract (stomach, duodenum, colon) immunostained
      with chromogranin A and serotonin revealed a widespread reduction or complete
      loss of EE cells in all four patients with APECED syndrome suffering from severe
      diarrhea, vomiting, malabsorption, or constipation. In contrast, EE cells were
      present in pediatric patients with similar gastrointestinal symptoms caused by
      inflammatory bowel disease, celiac disease, lymphocytic colitis, and autoimmune
      disorders without endocrinopathy or graft vs. host disease of the gut.
      CONCLUSIONS: The reduction of EE cells is a specific and important early event in
      the pathogenesis of APECED with GI dysfunction. We propose a diagnostic algorithm
      integrating clinics, genetics and immunohistology.

PMID- 22162466
TI  - The timing of total thyroidectomy in RET gene mutation carriers could be
      personalized and safely planned on the basis of serum calcitonin: 18 years
      experience at one single center.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-producing C
      cell tumor. In hereditary cases, a germline RET mutation is found in 98% of
      families. Because MTC is cured only if intrathyroidal, prophylactic thyroidectomy
      is recommended in the gene carrier (GC). AIMS: The aim was to determine whether
      thyroidectomy performed when stimulated CT becomes detectable is as safe as
      prophylactic thyroidectomy and to identify the serum CT cutoff able to
      distinguish intrathyroidal from extrathyroidal MTC. PATIENTS: Eighty-four GC were
      prospectively enrolled; 53 of the 84 underwent total thyroidectomy, one refused
      surgery, and 30 with normal basal and stimulated CT were under surveillance. The
      follow-up ranged from 2 to 18 yr. RESULTS: GC operated on for elevated stimulated
      CT included 27 GC with a positive peak CT at the screening and four cases who
      became positive after 4 yr. All of them had intrathyroidal MTC and no node
      metastases; all were cured after a mean follow-up of 7.5 yr. Among those operated
      on for detectable basal CT, intrathyroidal tumors were found when CT was below 60
      pg/ml, whereas either node metastases or larger tumors were observed when CT was
      above 60 pg/ml. No correlation among serum CT, age, and type of RET mutation was
      observed. Thirty GC were still biochemically negative at the annual control.
      CONCLUSIONS: The time of thyroidectomy in GC with negative CT could be
      personalized and safely planned when stimulated CT becomes positive, independent
      of the type of RET mutation and patient's age. In this series, a basal CT below
      60 pg/ml was always associated to an intrathyroidal localization of MTC.

PMID- 22162467
TI  - Muscle-bone characteristics in children with Prader-Willi syndrome.
AB  - BACKGROUND: A decrease in muscle mass, low motor performance, and normal lumbar
      spine bone mineral density (BMD) have been reported in children with Prader-Willi
      syndrome (PWS). However, these data are limited by the fact that PWS children
      (who have short stature) were compared to age-matched healthy or obese
      individuals of normal height. OBJECTIVE: The goal of the present study was to
      compare bone and muscle characteristics in PWS children to sex- and age- or
      height-matched healthy subjects. MATERIALS AND METHODS: The study population
      included 17 PWS children (ages 6.2 to 17.5 yr; nine girls) who were not treated
      with GH. The axial skeleton was analyzed at the lumbar spine using dual-energy x
      ray absorptiometry, and the appendicular skeleton (radius and tibia) was
      evaluated using peripheral quantitative computed tomography. Muscle parameters
      (mass, size, and functional parameters) were measured by dual-energy x-ray
      absorptiometry, peripheral quantitative computed tomography, and jumping
      mechanography, respectively. RESULTS: Compared to height-matched controls, PWS
      patients had normal axial and appendicular BMD, as well as normal muscle size.
      Compared to age- or height-matched controls of normal weight, PWS patients had
      lower maximal muscle force and power relative to body mass during jumping. PWS
      patients had similar absolute maximal muscle force but lower absolute maximal
      power compared to age- or height-matched controls. Relationships between bone
      mass and muscle size and force were similar in PWS patients and in healthy
      subjects. CONCLUSION: Relative to their height, PWS patients not treated with GH
      had normal axial and appendicular BMD, muscle size, and muscle-bone
      relationships.

PMID- 22162468
TI  - Age-specific reference ranges for serum testosterone and androstenedione
      concentrations in women measured by liquid chromatography-tandem mass
      spectrometry.
AB  - OBJECTIVE: RIA-based sex hormone measurements offer only limited precision and
      specificity in the low concentration range of women. Therefore, we aimed to
      establish age-specific reference ranges for serum sex hormone concentrations in
      women using mass spectrometry and quantile regression. METHODS AND RESULTS: Data
      from 985 women aged 20-80 yr, recruited for the prospective Study of Health in
      Pomerania, were included in the analyses. Quantile regressions models were
      performed to calculate the age-specific 2.5th and 97.5th percentiles for sex
      hormone concentrations in women. Serum total testosterone (TT) and
      androstenedione (AD) concentrations were measured by liquid chromatography-tandem
      mass spectrometry. Measured concentrations of SHBG and TT were used to calculate
      free testosterone (free T). TT, AD, and free T concentrations showed a distinct
      age-related decline across 10-yr age groups (one way ANOVA P < 0.001). Sex
      hormone reference ranges for TT, AD, and free T were determined across each
      single year of age and for 10-yr age groups. Reference ranges over the whole age
      range of 20-80 yr were 0.35-1.97 nmol/liter for TT, 0.89-4.56 nmol/liter for AD,
      and 0.0025-0.0253 nmol/liter for free T. Separate reference ranges were provided
      for pre- and postmenopausal women as well as after inclusion of women using oral
      contraceptives or hormone therapy (n = 1357). CONCLUSION: This is the first study
      to establish age-specific reference ranges for liquid chromatography-tandem mass
      spectrometry-measured TT and AD and calculated free T concentrations based on
      quantile regression analyses, accurately accounting for the observed low
      concentration range and the strong age dependency of these sex hormones in women.

PMID- 22162469
TI  - (111)In-octreotide scintigraphy for identification of metastatic medullary
      thyroid carcinoma in children and adolescents.
AB  - CONTEXT: Most medullary thyroid cancers (MTC) express somatostatin receptors;
      therefore, (111)In-octreotide somatostatin receptor scintigraphy (SRS) may be
      useful in detecting sites of metastases in children with MTC. OBJECTIVE: The aim
      of the study was to evaluate tumor metastases in children and adolescents with
      MTC using SRS in comparison to conventional imaging. DESIGN AND SETTING: A case
      series was conducted as part of baseline evaluation for cancer treatment protocol
      at the National Institutes of Health Clinical Center. PATIENTS: Eleven patients
      with a median age of 15 (range, 9-17) yr participated in the study, 10 with
      histologically proven, metastatic MTC due to the M918T mutation of the RET
      protooncogene, and one with a known RET polymorphism. INTERVENTION: After
      receiving 0.086 mCi/kg (111)Indium-pentreotide, patients were examined with a
      single photon emission computed tomography scan 4 and 24 h after injection.
      Baseline conventional imaging, including computed tomography (neck, chest,
      abdomen, +/- pelvis, adrenals), magnetic resonance imaging (neck), and bone scan,
      was performed on all patients. MAIN OUTCOME MEASURES: SRS results were compared
      with conventional imaging. RESULTS: Five of the 11 patients had abnormal findings
      on SRS. Of the 53 total target lesions present in the patients, only 24.5% were
      accurately identified through SRS. CONCLUSIONS: SRS appears to be less sensitive
      than conventional imaging at detecting the full extent of metastatic disease in
      children and adolescents with hereditary MTC. SRS incompletely identified sites
      of tumor and failed to visualize small sites of tumor or liver and lung
      metastases, and it has a limited role in the evaluation of metastatic disease in
      pediatric MTC patients.

PMID- 22162470
TI  - Subcutaneous adipose tissue remodeling during the initial phase of weight gain
      induced by overfeeding in humans.
AB  - CONTEXT: Deciphering the early processes occurring in adipose tissue during
      weight gain is a major issue for understanding the development of fat mass and
      obesity. Experimental overfeeding in humans is a unique situation to tackle these
      events. OBJECTIVE: Our aim was to identify the pathways involved in sc adipose
      tissue remodeling during the initial phase of weight gain. RESEARCH DESIGN AND
      METHODS: Forty-four healthy men were involved in an overfeeding protocol with a
      lipid-enriched diet (+760 kcal/d) for 2 months. Subcutaneous abdominal adipose
      tissue biopsies were taken for histology, transcriptomics, and Western blotting
      in the basal state, after 14 d, and at the end of the protocol. RESULTS:
      Overfeeding significantly increased body weight (+2.5 kg) and fat mass.
      Reorganization of gene expression patterns occurred in adipose tissue with an up
      regulation of numerous genes involved in lipid metabolism and storage, followed
      by clusters of genes related to angiogenesis and extracellular matrix remodeling.
      Histological examination showed increased microvascular density and connective
      tissue deposition after 56 d of overfeeding, with no changes in the number of
      macrophages or inflammatory cells. Inhibition of the canonical Wnt/beta-catenin
      signaling pathway and induction of the renin-angiotensin system might be
      implicated in the remodeling of sc adipose tissue. CONCLUSIONS: We characterize
      the coordinated and time-dependent processes that occur in human adipose tissue
      during the early phase of weight gain in healthy subjects and identify pathways
      representing potential targets in pathologies of adipose development, including
      obesity.

PMID- 22162471
TI  - Verbal and visual memory performance and hippocampal volumes, measured by 3-Tesla
      magnetic resonance imaging, in patients with Cushing's syndrome.
AB  - CONTEXT: Cushing's syndrome (CS) affects cognition and memory. OBJECTIVE: Our
      objective was to evaluate memory and hippocampal volumes (HV) on 3-tesla magnetic
      resonance imaging (3T MRI) in CS patients and controls. PATIENTS AND METHODS:
      Thirty-three CS patients (11 active, 22 cured) and 34 controls matched for age,
      sex, and education underwent Rey Auditory Verbal Learning Test and Rey-Osterrieth
      Complex Figure memory tests. Gray matter and HV were calculated on 3T MRI, using
      FreeSurfer image analyses software. RESULTS: No differences in HV were observed
      between active and cured CS or controls. Memory performance was worse in CS
      patients than controls (P < 0.04 in active; P < 0.03 in cured CS) but did not
      differ among CS groups, which were therefore analyzed together; they performed
      worse for verbal (P = 0.02) and visual memory (P = 0.04) than controls. In 12 CS
      patients, memory was below normative cutoff values for verbal (n = 6, cured),
      visual memory (n = 10, six cured) or both (n = 4); these patients with severe
      memory impairments showed smaller HV compared with their matched controls (P =
      0.02 with verbal impairment; P = 0.03 with visual impairment). They were older (P
      = 0.04), had shorter education (P = 0.02), and showed a trend toward longer
      duration of hypercortisolism (P = 0.07) than the remaining CS patients. Total (P
      = 0.004) and cortical (P = 0.03) brain gray matter volumes were decreased in CS
      compared with controls, indicating brain atrophy, whereas subcortical gray matter
      (which includes HV) was reduced only in the 12 patients with severe memory
      impairment. CONCLUSION: Verbal and visual memory is worse in CS patients than
      controls, even after biochemical cure. HV was decreased only in those whose
      memory scores were below normative cutoff values.

PMID- 22162472
TI  - Growth hormone receptor variants and response to pegvisomant in monotherapy or in
      combination with somatostatin analogs in acromegalic patients: a multicenter
      study.
AB  - CONTEXT: The influence of full-length GH receptor (GHR) and exon 3-deleted GHR
      (d3GHR) on responsiveness to pegvisomant (PEG-V) in acromegalic patients is
      uncertain. OBJECTIVE: The aim of the study was to assess the distribution of GHR
      genotypes in a large series of patients on PEG-V therapy and their influence on
      treatment efficacy and adverse effects. DESIGN AND SETTING: A cross-sectional
      multicenter pharmacogenetic study was conducted in 16 Italian endocrinology
      centers of major universities and tertiary care hospitals. PATIENTS: The study
      included 127 acromegalic patients enrolled from 2009 to 2010 not cured by
      previous surgery, radiotherapy, and long-acting somatostatin (SST) analogs,
      treated with PEG-V. INTERVENTION AND MAIN OUTCOME MEASURE: Sixty-three of 127
      patients received combined PEG-V + SST analog therapy. Clinical and hormonal data
      at diagnosis and before and during PEG-V therapy were inserted in a database. GHR
      exon 3 deletion and other polymorphisms were genotyped by the coordinator center.
      Differences in PEG-V dosage required for IGF-I normalization and occurrence of
      adverse effects between carriers and noncarriers of GHR variants were evaluated.
      RESULTS: d3GHR variants were not in Hardy-Weinberg equilibrium (P = 0.008). No
      association of these variants with PEG-V dose required for IGF-I normalization,
      adverse effects occurrence, and tumor regrowth was found in patients on PEG-V and
      on PEG-V + SST analog treatment. Similar data were obtained considering the GHR
      variant rs6180. CONCLUSIONS: This study did not confirm a better response of
      d3GHR to PEG-V treatment in acromegaly. Other studies are needed to determine
      whether deviation from Hardy-Weinberg equilibrium may indicate an association of
      d3GHR genotype with poor response to usual treatments.

PMID- 22162473
TI  - The roles of prostaglandin EP 1 and 3 receptors in the control of human
      myometrial contractility.
AB  - CONTEXT: Prostaglandins are central to the processes of human labor.
      Prostaglandin E(2) (PGE(2)) synthesized within the uterus mediates cervical
      ripening and uterine contractions. PGE receptors, EP1 and EP3, may each mediate
      contractions, and represent potential therapeutic targets in the management of
      preterm labor. Studies of the expression and function of EP1 and EP3 in pregnant
      myometrium are inconsistent. OBJECTIVE: The objective of the study was to
      determine the relative importance of EP1 and EP3 in human myometrial
      contractility. DESIGN: We studied the expression of EP1 and EP3 in upper- and
      lower-segment myometrium at term in vivo and the effects of specific inhibitors
      on contractions in vitro. PATIENTS: Myometrial biopsies for both in vivo and in
      vitro studies were taken at cesarean section at term before or in labor in
      uncomplicated pregnancies. RESULTS: We found no differences in the expression of
      EP1 or EP3 at mRNA or protein level between the upper and lower segment
      myometrium and no overall changes associated with the onset of labor. Upon labor,
      EP1, but not EP3, was found to relocalize to the nucleus. In studies of
      contractility, we found no differences in spontaneous or PGE(2)-induced
      contractility between the upper- and lower-segment samples. Spontaneous
      contractions were inhibited by acetylsalicylic acid and were rescued by PGE(2).
      Although an EP1 antagonist, ZD6416, had no effect, an EP3 antagonist, L798106,
      inhibited both spontaneous and PGE(2)-induced contractions. CONCLUSIONS: EP3 is
      the primary receptor subtype that mediates PGE(2) induced contractility in human
      pregnant myometrium at term and represents a possible therapeutic target.

PMID- 22162474
TI  - Effect of gestational diabetes and intrauterine growth restriction on the
      offspring's circulating galanin at birth.
AB  - CONTEXT: Experimental studies linked gestational diabetes mellitus (GDM) and
      intrauterine growth restriction (IUGR) with altered expression of the offspring's
      hypothalamic galanin mRNA, possibly contributing to the development of obesity
      and metabolic syndrome in later life. We hypothesized that plasma galanin levels
      at birth would reflect presumably altered hypothalamic galanin expression and
      production that cannot be assessed in the human offspring. OBJECTIVE: Our
      objective was to investigate whether neonates born to GDM mothers or being IUGR
      differ from healthy ones in circulating galanin at birth. DESIGN, PATIENTS, AND
      METHODS: Twenty-five neonates born to GDM mothers, 25 with IUGR, and 15 healthy
      neonates (controls) were prospectively studied. Neonatal plasma galanin levels
      were assayed immediately after birth by using enzyme immunoassay. RESULTS:
      Neonatal plasma galanin showed a high variability within each group and did not
      differ significantly among the three groups of neonates. No correlation between
      plasma galanin and anthropometric maternal and neonatal data was found. Multiple
      linear regression confirmed that the neonatal group (infants of diabetic mothers,
      IUGR, and controls) was not an independent predictor for galanin levels at birth
      after controlling for possible confounders, i.e. maternal body mass index and
      weight gain during pregnancy and neonatal body mass index. CONCLUSIONS:
      Circulating galanin levels at birth are not affected by GDM and IUGR, providing
      no evidence for alternations in hypothalamic galanin expression and secretion in
      humans, as they were previously documented in experimental models. This fact
      precludes the use of plasma galanin as an early indicator for the development of
      obesity and metabolic syndrome in this high-risk population.

PMID- 22162475
TI  - Androgen deprivation therapy as primary treatment for prostate cancer.
AB  - CONTEXT: Hormonal therapy has been the mainstay of treatment for advanced
      prostate cancer for over 70 yr. The timing and extent of androgen ablative
      therapy for earlier stage disease remains controversial. In addition, recent
      studies demonstrate that so-called "castration-resistant" tumors are still
      dependent on androgen receptor signaling. PATIENT AND METHODS: A 66-yr-old man
      presented with clinical stage T1C N+ M0 prostate cancer and received primary
      androgen deprivation therapy. Over the course of the next 17 yr, he was treated
      with various forms of androgen deprivation therapy, including two newer agents,
      abiraterone acetate and MDV 3100. A review of the literature was conducted to
      identify indications, controversies, and new developments regarding hormonal
      therapy for prostate cancer. CONCLUSIONS: Androgen deprivation therapy remains
      the treatment of choice for metastatic prostate cancer; however, it is not
      without its adverse effects, and most men with advanced disease eventually
      develop castration resistance. Newer compounds that more specifically and
      effectively target androgen and androgen receptor signaling in prostate cancer
      cells may provide more long-lasting remissions in advanced disease.

PMID- 22162476
TI  - Effect of intranasal insulin on cognitive function: a systematic review.
AB  - AIM: Epidemiological and mechanistic studies raised the possibility that
      cognitive function may be affected by brain responses to insulin. We
      systematically reviewed and analyzed existing clinical trials that assessed the
      potential beneficial effects of intranasal insulin administration on cognitive
      functions. METHODS: Interventional studies measuring changes in cognitive
      functions in response to intranasal insulin were retrieved and included if they
      were in English and assessed cognitive functions before and after treatment.
      Cohen's effect size was calculated to allow comparison between studies. RESULTS:
      Eight studies (328 participants) were analyzed. No significant side effects of
      intranasal insulin administration were reported. Seven studies included healthy
      subjects' response to intranasal insulin, and three evaluated the cognitive
      effect among patients with minimal cognitive impairment or overt Alzheimer's
      disease. In healthy people, Cohen's effect size calculations suggest that only
      160 IU/d intranasal insulin induced potential beneficial effects. Although
      females, when compared head-to-head, exhibited greater improvements in cognitive
      tests than men, the composite analysis of all included studies did not support
      this trend. Among cognitively impaired patients, only lower doses of insulin were
      assessed, and 20 IU revealed potential beneficial effects on cognitive functions.
      This was significant in a single study assessing long-term intranasal insulin
      administration, whereas acute administration of 20 IU intranasal insulin tended
      to show a beneficial effect on immediate recall in Apo epsilon4(-), but not Apo
      epsilon4(+), patients. CONCLUSIONS: The current limited clinical experience
      suggests potential beneficial cognitive effects of intranasal insulin. Analyses
      provide clinical considerations for future research aimed at elucidating whether
      intranasal insulin may be used to improve cognitive functions.

PMID- 22162477
TI  - Maternal early pregnancy and newborn thyroid hormone parameters: the Generation R
      study.
AB  - CONTEXT: Abnormal maternal thyroid parameters are associated with adverse
      pregnancy outcomes, with consequences for both mother and child. Although various
      studies have studied maternal thyroid parameters during the first half of
      pregnancy, little is known about their relations with thyroid parameters of the
      child. OBJECTIVE: The objective was to study maternal thyroid parameters during
      the first half of pregnancy as well as their relations with cord thyroid
      parameters. DESIGN, SETTING, AND PARTICIPANTS: Serum TSH, free T(4) (FT4), T(4),
      and thyroid peroxidase antibody (TPOAb) levels were determined once between
      gestational wk 9 and 18 in 5393 pregnant women from the population-based
      Generation R study. Cord serum TSH and FT4 levels were determined in 3036
      newborns. RESULTS: Between gestational wk 9 and 18, the maternal TSH reference
      range (2.5th to 97.5th percentile) was 0.03-4.04 mU/liter. Gestational age was
      positively correlated with maternal TSH (r = 0.06, P = 6.3 * 10(-5)) and total
      T(4) (r = 0.21, P = 1.4 * 10(-44)) and negatively with FT4 (r = -0.27, P=7.3 *
      10(-76)) and TPOAb-positivity (r=-0.04, P = 0.01). TPOAb positivity was
      associated with more subclinical (20.1 vs. 2.4%, P = 1.5 * 10(-39)) and overt
      hypothyroidism (3.3 vs. 0.1%, P = 1.4 * 10(-10)). Maternal and cord TSH were
      positively associated (beta = 0.47 +/- 0.15, P = 1.3 * 10(-5)) as well as
      maternal and cord FT4 (beta = 0.11 +/- 0.02, P = 4.5 * 10(-6)). CONCLUSIONS: We
      confirm correlations of maternal thyroid parameters with gestational age during
      the first half of pregnancy and show a substantially increased risk of
      (subclinical) hypothyroidism in TPOAb-positive mothers. A substantial part of the
      mothers had a TSH level above 2.5 mU/liter, underlining the importance of using
      population-specific reference ranges. Maternal and cord thyroid parameters were
      positively correlated, the exact biological basis of which remains to be
      determined.

PMID- 22162479
TI  - Alteration of the circadian clock in children with Smith-Magenis syndrome.
AB  - CONTEXT: Smith-Magenis syndrome (SMS) is associated with sleep disturbances and
      disrupted melatonin production. OBJECTIVES: The study aimed to ascertain whether
      the sleep and melatonin production anomalies in SMS patients may be due to an
      alteration of the molecular mechanism of the circadian clock. SUBJECTS AND
      METHODS: Five SMS patients (3-17 yr old) and five healthy age-matched control
      subjects were involved in the study. Saliva and buccal scrub samples were
      collected every 4 h during a 24-h period. Daily profiles of melatonin were
      determined in saliva using a direct double-antibody radioimmunoassay. Daily
      profiles of clock gene mRNA levels (Per1, Per2, and Rev-erbalpha) were determined
      in buccal scrub samples by RT-PCR. RESULTS: In controls, melatonin levels were
      elevated during the nighttime and very low during the daytime. Daily profiles of
      clock genes, Per1, Per2, and Rev-erbalpha, mRNA levels in buccal mucosa exhibited
      significant and mutually synchronized circadian variations (Per1 and Rev
      erbalpha: P < 0.001; Per2: P < 0.05); the mRNA levels were elevated during the
      daytime and decreased during the nighttime. In SMS patients, melatonin profiles
      were significantly altered compared with controls, being phase reversed, phase
      advanced, depressed, or abolished. Only Per1 and Rev-erbalpha mRNA profiles
      exhibited significant circadian rhythms (P < 0.05); the Per2 expression exhibited
      high variability, and the profile was out of phase with the other clock genes.
      CONCLUSION: Our findings suggest that the anomalies in melatonin profiles of SMS
      patients might be due to a disturbance of the molecular circadian clockwork.

PMID- 22162480
TI  - Adipose tissue depot-specific differences in the regulation of hyaluronan
      production of relevance to Graves' orbitopathy.
AB  - CONTEXT: Graves' orbitopathy (GO) is associated with Graves' disease, in which
      anti-TSH receptor (TSHR) autoantibodies (thyroid-stimulating antibodies) increase
      cAMP causing hyperthyroidism. Excess adipogenesis and hyaluronan (HA)
      overproduction [HA synthase 2 (HAS2) is the major source] expand the orbital
      contents causing GO. TSHR activation participates in both processes but an anti
      TSHR monoclonal without TSAB activity also increased HA, suggesting the
      involvement of other cascades. OBJECTIVE AND PATIENTS STUDIED: We investigated
      using in vitro models in which preadipocytes/fibroblasts from human orbital (n =
      12) and sc (n = 10) adipose tissues were treated with IGF-I (to probe the pAkt
      pathway, recently identified as a positive regulator of HAS2), TSH, and/or
      various inhibitors. Changes in HA during in vitro-induced adipogenesis were also
      evaluated. MAIN OUTCOME AND RESULTS: Adipogenesis in orbital preadipocytes was
      accompanied by significantly increased HAS2 transcripts and HA accumulation in
      contrast to sc cells in which differentiation significantly decreased HAS2 mRNA
      and secreted HA. Surprisingly, IGF-I alone did not increase HAS2 levels, despite
      significantly increasing the ratio of phosphorylated to total Akt; furthermore,
      an Akt inhibitor increased orbital (but not sc) HAS2 transcripts. A stimulatory
      effect of IGF-I on HAS2 transcripts was revealed by addition of rapamycin in sc
      but by a MAPK kinase inhibitor in orbital fibroblasts. CONCLUSIONS: The results
      have several possible explanations including a phosphorylation-dependent
      repressor of HAS2 transcript accumulation, exclusively in the orbit. The
      difference in control of HAS2 expression allows the activation of one of the
      mechanisms underlying GO, adipogenesis, to be linked biologically with the
      second, HA overproduction.

PMID- 22162481
TI  - Three-year efficacy and safety of LB03002, a once-weekly sustained-release growth
      hormone (GH) preparation, in prepubertal children with GH deficiency (GHD).
AB  - BACKGROUND: GH treatment currently requires daily sc injections, resulting in
      suboptimal compliance. A GH regimen with fewer injections may offer patients and
      caregivers a less arduous option. LB03002 is a novel sustained-release GH
      formulation for once-weekly dosing. PATIENTS AND METHODS: GH-deficient, GH-naive
      prepubertal children were randomized to four groups who received 0.2 mg/kg/wk
      LB03002 for 12 months, followed by 0.5 mg/kg/wk for another 24 months (n=13); 0.5
      mg/kg/wk LB03002 for 36 months (n=13); 0.7 mg/kg/wk LB03002 for 12 months,
      followed by 0.5 mg/kg/wk for another 24 months (n=13); or daily GH 0.03 mg/kg/d
      for 24 months, switched to 0.5 mg/kg/wk LB03002 for 12 months (n = 12). RESULTS:
      Height velocity increased in all groups; the increase was less for the 0.2
      mg/kg/wk LB03002 group at 12 (P = 0.008) and 24 months (P = 0.030), with no
      statistically significant differences at any time for the 0.5 mg/kg/wk and 0.7
      mg/kg/wk LB03002 groups, vs. daily GH. Height sd score gain at 12 months was
      significantly (P = 0.023) less for the 0.2 mg/kg/wk group (1.05 +/- 0.38) than
      daily GH (1.47 +/- 0.29), but with no statistically significant difference for
      the 0.5 mg/kg/wk (1.37 +/- 0.39) and 0.7 mg/kg/wk (1.50 +/- 0.44) LB03002 groups
      vs. daily GH. There were no significant differences in height sd score gain
      between any groups at 24 and 36 months. Bone maturation did not differ for any
      LB03002 dose compared with daily GH. Serum IGF-I concentrations increased as
      expected, with no long-term differences between groups. Mean fasting glucose and
      glycosylated hemoglobin concentrations did not exceed normal ranges for any
      treatment group at any time. CONCLUSION: LB03002 at doses of 0.5 mg/kg/wk and 0.7
      mg/kg/wk was shown to be effective and safe with once-weekly dosing in GH
      deficient children, and 0.5 mg/kg/wk LB03002 was chosen as the optimal dose for
      long-term assessment.

PMID- 22162478
TI  - Genotype-phenotype analysis in congenital adrenal hyperplasia due to P450
      oxidoreductase deficiency.
AB  - CONTEXT: P450 oxidoreductase deficiency (PORD) is a unique congenital adrenal
      hyperplasia variant that manifests with glucocorticoid deficiency, disordered sex
      development (DSD), and skeletal malformations. No comprehensive data on genotype
      phenotype correlations in Caucasian patients are available. OBJECTIVE: The
      objective of the study was to establish genotype-phenotype correlations in a
      large PORD cohort. DESIGN: The design of the study was the clinical, biochemical,
      and genetic assessment including multiplex ligation-dependent probe amplification
      (MLPA) in 30 PORD patients from 11 countries. RESULTS: We identified 23 P450
      oxidoreductase (POR) mutations (14 novel) including an exonic deletion and a
      partial duplication detected by MLPA. Only 22% of unrelated patients carried
      homozygous POR mutations. p.A287P was the most common mutation (43% of unrelated
      alleles); no other hot spot was identified. Urinary steroid profiling showed
      characteristic PORD metabolomes with variable impairment of 17alpha-hydroxylase
      and 21-hydroxylase. Short cosyntropin testing revealed adrenal insufficiency in
      89%. DSD was present in 15 of 18 46,XX and seven of 12 46,XY individuals.
      Homozygosity for p.A287P was invariably associated with 46,XX DSD but normal
      genitalia in 46,XY individuals. The majority of patients with mild to moderate
      skeletal malformations, assessed by a novel scoring system, were compound
      heterozygous for missense mutations, whereas nearly all patients with severe
      malformations carried a major loss-of-function defect on one of the affected
      alleles. CONCLUSIONS: We report clinical, biochemical, and genetic findings in a
      large PORD cohort and show that MLPA is a useful addition to POR mutation
      analysis. Homozygosity for the most frequent mutation in Caucasians, p.A287P,
      allows for prediction of genital phenotype and moderate malformations. Adrenal
      insufficiency is frequent, easily overlooked, but readily detected by cosyntropin
      testing.

PMID- 22162482
TI  - The role of autoantibodies to zinc transporter 8 in prediction of type 1 diabetes
      in relatives: lessons from the European Nicotinamide Diabetes Intervention Trial
      (ENDIT) cohort.
AB  - CONTEXT: Antibodies to islet autoantigens are detectable many years before
      clinical onset of type 1 diabetes and can be used to identify individuals at
      increased risk of diabetes. Zinc transporter 8 is a recently identified islet
      autoantigen. OBJECTIVE: Our aim was to determine whether addition of zinc
      transporter 8 autoantibodies (ZnT8A) improved prediction of type 1 diabetes in a
      well-characterized cohort of islet cell antibody (ICA)-positive first-degree
      relatives. We were particularly interested in the role of ZnT8A in prediction in
      antibody-positive relatives with intermediate and low overall risk of diabetes.
      PARTICIPANTS AND METHODS: ZnT8A were assayed in baseline samples from 526 ICA
      positive first-degree relatives randomized in the European Nicotinamide Diabetes
      Intervention Trial. Antibodies to insulin, glutamate decarboxylase, islet antigen
      2 (IA-2A) and IA-2beta (IA-2betaA), and human leukocyte antigen type had been
      previously determined. Risk of diabetes was assessed by survival analysis.
      RESULTS: Of 221 ZnT8A-positive individuals, 113 developed diabetes during follow
      up (5-yr cumulative risk, 55%). In multivariate models based on other
      autoantibodies, ZnT8A improved prediction in relatives at low genetic risk of
      diabetes (P = 0.030) and over age 20 yr (P = 0.026), but not in those with ICA
      alone or with one additional autoantibody (P = 0.696), IA-2A-negative relatives
      (P = 0.361), those at high or intermediate genetic risk, or younger relatives.
      CONCLUSIONS: ZnT8A are useful additional risk markers in relatives at low genetic
      risk of diabetes and older individuals, but they add relatively little in younger
      populations because of the precise prediction possible with current autoantibody
      combinations.

PMID- 22162484
TI  - The impact of reflux burden on Pseudomonas positivity in children with cystic
      fibrosis.
AB  - OBJECTIVES: Nonacid gastroesophageal reflux (GER), particularly in patients
      taking acid suppression, has been implicated as a cause of respiratory
      infections. We hypothesize that children with cystic fibrosis (CF) and a higher
      nonacid reflux burden have greater rates of Pseudomonas aeruginosa (Pa) infection
      than patients with a lower reflux burden. STUDY DESIGN: We reviewed the
      multichannel intraluminal impedance (pH-MII) tracings of 35 patients with CF
      between 2003 and 2010. We compared the reflux profiles between those patients who
      were Pa positive and Pa negative. RESULTS: The mean age was 13.5 +/- 5.8 years.
      Twenty-seven patients (76%) were Pa positive. Ninety seven percent of patients
      were taking proton pump inhibitors during pH-MII testing. The mean percentage of
      time pH was <4 was 8.5 +/- 12%. Pa patients had a significantly higher total,
      acid and proximal nonacid reflux burden (P < 0.009). There was a negative
      correlation between nonacid reflux burden and FEV1 (r = -0.397, P = 0.03) and
      between total number of reflux events and FEV1 (r = -0.474, P = 0.009). After
      adjusting for age and FEV1, total reflux burden remains significantly associated
      with Pa positivity (P = 0.055). CONCLUSIONS: Increased reflux burden may
      predispose patients to Pa infection and worse lung function.

PMID- 22162485
TI  - CO oxidation at the perimeters of an FeO/Pt(111) interface and how water promotes
      the activity: a first-principles study.
AB  - The catalytic role of the Pt--Fe cation ensemble presented at the perimeters of
      the FeO film supported on Pt(111) for low-temperature CO oxidation and the
      promotion of water on activity were studied by using DFT calculations. We found
      that the perimeter sites along the edge of the FeO islands on Pt provided a
      favorable ensemble that consisted of coordinatively unsaturated ferrous species
      and nearby Pt atoms for O(2) and H(2) O activation free from CO poison. A
      dissociative oxygen atom at the Pt--Fe cation ensemble reacts easily with CO
      adsorbed on nearby Pt. The OH group from water dissociation not only facilitates
      activation of the oxygen molecule, more importantly it opens a facile reaction
      channel for CO oxidation through the formation of the carboxyl intermediate. The
      presence of the OH group on the FeO film strengthens interfacial interactions
      between FeO and Pt(111), which would make the FeO film more resistant to further
      oxidation. The importance of the Pt--Fe cation ensemble and the role of water as
      a cocatalyst for low-temperature CO oxidation is highlighted.

PMID- 22162486
TI  - The prevalence of sleepiness and the risk of sleep-disordered breathing in
      children with positive allergy test.
AB  - BACKGROUND: We evaluated the prevalence of sleep-disordered breathing (SDB) and
      sleepiness in children with allergy and compared sleep-specific quality of life
      measures to those of children without allergy. METHODS: A prospective case
      control study was done at a tertiary care academic center. The parents of 21
      pediatric patients with positive environmental allergy testing completed
      questionnaires including the Obstructive Sleep Apnea-18 (OSA18), the Pediatric
      Sleep Questionnaire (PSQ), and the Pediatric Daytime Sleepiness Scale (PDSS).
      Comparisons were made to 113 children without allergy who had undergone cochlear
      implantation (CI) who served as controls. RESULTS: SDB was suggested in 19% of
      children with allergy using the OSA18 and in 29% using the PSQ vs 6% and 7% of
      controls (p = 0.029; p = 0.003), respectively. In addition, daytime sleepiness
      was suggested in 45% to 48% of children with allergy using the PSQ and PDSS vs
      17% to 25% of controls (p = 0.015; p = 0.025), respectively. Patients with
      allergy had SDB and sleepiness scores higher than population normal values: OSA
      18 of 41.7 vs 34.0, PSQ-SDB of 0.25 vs 0.14, PSQ-Sleepy of 0.34 vs 0.15, and PDSS
      of 14.2 vs 11.4. The difference between cases and controls was significant for
      all measures of sleepiness and SDB. CONCLUSION: Children with allergy have higher
      SDB and sleepiness scores than controls. This suggests that children with
      allergic rhinitis are at increased risk for SDB and screening should be
      considered in this population. In addition, studies with a larger sample size are
      important to fully understand this relationship.

PMID- 22162487
TI  - Supramolecular aggregation/disaggregation-based molecular sensing: a review
      focused on investigations from China.
AB  - Supramolecular aggregation and disaggregation induced by external stimuli can
      impact the optical or electrical signals of the aggregates/constituting units
      (receptors). Therefore, manipulating supramolecular aggregation/disaggregation
      has recently been employed to construct novel and promising photoluminescence
      (PL)-based sensing and recognition systems. The sensing systems were capable of
      substantially enhancing the sensitivity, relying on cooperative interactions
      occurring in the assembly/disassembly processes (mostly operating in emission
      turned-on or emission-enhanced mode). This review focuses mainly on recent
      advances in the new emerging PL-based sensing platforms, based on manipulating
      the behaviours of supramolecular aggregation/disaggregation, including
      aggregation-induced emission (AIE), metallophilic interactions-related sensing
      (metallophilic interactions-induced aggregation/disaggregation), metal
      coordination polymers-related sensing, and other sensing systems involving
      supramolecular aggregation/disaggregation. In particular, those sensing systems
      developed by scientists in China are summarized and highlighted.

PMID- 22162488
TI  - Enantioselective determination of triazole fungicide tebuconazole in vegetables,
      fruits, soil and water by chiral liquid chromatography/tandem mass spectrometry.
AB  - A novel and sensitive method was developed for the determination of tebuconazole
      enantioselectively using reversed-phase LC-MS/MS. The separation and
      determination were performed using on an amylose-based chiral stationary phase, a
      Lux 3u Amylose-2 column (150 mm*2.0 mm), under isocratic conditions at 0.3 mL/min
      flow rate. A series of chiral stationary phases were investigated and the effect
      of mobile phase composition on the enantioseparation was discussed. Parameters
      including the matrix effect, linearity, precision, accuracy and stability were
      evaluated. Under optimal conditions, the overall mean recoveries for two
      enantiomers from the soil, tomato, cucumber, pear and apple samples were 79.3
      101.1% with 2.8-11.5% intra-day relative standard deviations (RSDs) and 4.1-8.6%
      inter-day RSDs at 5, 25 and 50 MUg/kg levels; the mean enantiomer recoveries from
      the water samples were 89.6-101.9% with 3.3-10.2% intra-day RSDs and 5.1-7.7%
      inter-day RSDs at 0.25, 0.5 and 2.5 MUg/kg levels. The limits of detection (LODs)
      for all enantiomers in tomato, cucumber, pear, apple, soil and water were less
      than 0.6 MUg/kg, whereas the limit of quantification (LOQ) did not exceed 2.0
      MUg/kg. The results indicate that this proposed method is convenient and reliable
      for the enantioselective determination of tebuconazole enantiomers in foods and
      environment samples. 

PMID- 22162490
TI  - Editorial: Scaffold-free cell-based approaches in biomedicine and biotechnology.

PMID- 22162493
TI  - Continous bioprocessing: an interview with Konstantin Konstantinov from Genzyme.
      Interviewed by Prof. Alois Jungbauer and Dr. Judy Peng.

PMID- 22162495
TI  - Advanced cell therapies with and without scaffolds.
AB  - Tissue engineering and regenerative medicine aim to produce tissue substitutes to
      restore lost functions of tissues and organs. This includes cell therapies,
      induction of tissue/organ regeneration by biologically active molecules, or
      transplantation of in vitro grown tissues. This review article discusses advanced
      cell therapies that make use of scaffolds and scaffold-free approaches. The first
      part of this article covers the basic characteristics of scaffolds, including
      characteristics of scaffold material, fabrication and surface functionalization,
      and their applications in the construction of hard (bone and cartilage) and soft
      (nerve, skin, blood vessel, heart muscle) tissue substitutes. In addition, cell
      sources as well as bioreactive agents, such as growth factors, that guide cell
      functions are presented. The second part in turn, examines scaffold-free
      applications, with a focus on the recently discovered cell sheet engineering.
      This article serves as a good reference for all applications of advanced cell
      therapies and as well as advantages and limitations of scaffold-based and
      scaffold-free strategies.

PMID- 22162496
TI  - Advances in cell-based biosensors using three-dimensional cell-encapsulating
      hydrogels.
AB  - Cell-based biosensors (CBBs) have emerged as promising biotechnical tools whereby
      various cell types can be used as basic sensing units to detect external stimuli.
      Specifically, CBBs have been applied in environmental monitoring, drug screening,
      clinical diagnosis and biosecurity. For these applications, CBBs offer several
      advantages over conventional molecular-based biosensors or living animal-based
      approaches, such as the capability to better mimic physiological situations, to
      enhance detection specificity and sensitivity, and to detect unknown compounds
      and toxins. On the other hand, existing CBBs suffer from several limitations,
      such as weak cell-substrate attachment, two-dimensional (2D) cell
      microenvironment, and limited shelf life. An emerging method for scaffold-free
      three-dimensional (3D) cell culture uses hydrogels to encapsulate cells. Advances
      in novel biomaterials and nano/microscale technologies have enabled encapsulation
      of cells in hydrogels to fabricate 3D CBBs, which hold great potential for
      addressing the limitation in existing 2D CBBs. Here, we present an overview of
      the emerging hydrogel-based CBBs, their applications in pathogen/toxin detection,
      drug screening and screening of cell-biomaterials interaction, and the associated
      challenges and potential solutions.

PMID- 22162498
TI  - Tracheal synovial sarcoma in a 10-year-old child with stridor.

PMID- 22162499
TI  - Appropriate diuretic dosing: closed loop communication.

PMID- 22162500
TI  - We can learn much from the air force.

PMID- 22162501
TI  - Femoral hernias.

PMID- 22162502
TI  - Environmental risks of breast cancer remain uncertain.

PMID- 22162503
TI  - Scans, misogyny, and miscarriage.

PMID- 22162504
TI  - Surgical patients are not receiving the care they should, finds inquiry.

PMID- 22162505
TI  - Too much is spent on older people's healthcare and too little on their social
      care, MPs are told.

PMID- 22162506
TI  - Lack of investment in regulatory science is part of "innovation gap," believes
      FDA commissioner.

PMID- 22162508
TI  - No pharmacokinetic interaction between lacosamide and valproic acid in healthy
      volunteers.
AB  - Two open-label, randomized, multiple-dose clinical studies evaluated the
      potential for pharmacokinetic interaction between the antiepileptic drugs
      lacosamide and valproic acid. The influence of lacosamide on valproic acid
      pharmacokinetics (trial A) and valproic acid on lacosamide pharmacokinetics
      (trial B) was investigated in 32 healthy male volunteers, 16 in each trial.
      Volunteers in trial A received valproic acid (300 mg bid) with randomization to
      either early or late addition of lacosamide (200 mg bid). Those in trial B
      received lacosamide (200 mg bid) with randomization to either early or late
      addition of valproic acid (300 mg bid). Area under the concentration-time curve
      during a 12-hour dosing interval at steady state (AUC(tau,ss)) and maximum steady
      state plasma drug concentration (C(max,ss)) were measured for each drug alone and
      together and tested for equivalence. The point estimates (90% confidence
      intervals) for AUC(tau,ss) and C(max,ss) were 104% (99%-109%) and 101% (97%
      107%), respectively, for valproic acid and 100% (98%-103%) and 101% (96%-107%),
      respectively, for lacosamide, which were within the generally accepted
      equivalence range of 80% to 125%. No changes in the rate or extent of absorption,
      terminal half-life, or time to maximum concentration were observed. These results
      suggest that lacosamide and valproic acid have no relevant pharmacokinetic drug
      drug interaction.

PMID- 22162509
TI  - Unusual pulmonary findings in mucolipidosis II.
AB  - We report undescribed pulmonary findings in a child with mucolipidosis II (ML
      II). Children with ML-II bear significant pulmonary morbidity that may include
      extensive pulmonary fibrosis, persistent hemosiderosis as well as pulmonary
      airway excrescences as they reach preschool age.

PMID- 22162510
TI  - Antibacterial properties of additives used in injection immunotherapy.
AB  - BACKGROUND: Previous studies have reviewed the safety of preparing and
      administering allergy injection immunotherapy in a physician's office, and showed
      no evidence of infectious complications. The current study examines the
      antimicrobial properties of the common additives used in preparation of multidose
      immunotherapy vials. METHODS: Vials were prepared with varying concentrations of
      glycerin (0-25%), phenol (0-0.4%) and combinations of glycerin with phenol. A
      standard inoculum of Staphylococcus aureus was introduced in each vial and
      incubated. Optical densities were measured and colony counts were performed at 24
      and 48 hours. Follow-up broth microdilution assays were performed using varying
      inocula of bacteria and the highest concentrations of additives to determine the
      number of bacteria for which these solutions were bacteriostatic and/or
      bactericidal. Optical densities were measured and colony counts were performed as
      in the vial assays. RESULTS: All vials with varying dilutions of glycerin,
      phenol, and their combination showed bacterial growth with the standard inoculum
      of Staphylococcus aureus. Visible turbidity and optical density were inversely
      related to additive concentration. Follow-up microdilution assays with differing
      concentrations of bacteria demonstrated bactericidal activity with inocula of 1 *
      10(3) colony forming units (CFU) of Staphylococcus aureus at clinically used
      concentrations of glycerin and phenol. CONCLUSION: Higher concentrations of
      additives show better inhibition of bacterial growth. Solutions containing
      glycerin showed superior bactericidal activity than those containing only phenol.
      At concentrations of additives used in preparing allergy immunotherapy vials,
      antibacterial effects were observed with inoculation of 1 * 10(3) CFU or less of
      Staphylococcus aureus.

PMID- 22162512
TI  - Preparation and selective recognition of a novel solid-phase microextraction
      fiber combined with molecularly imprinted polymers for the extraction of parabens
      in soy sample.
AB  - A prepared molecularly imprinted polymer with ethyl p-hydroxybenzoate as template
      molecule was applied for the first time to a homemade solid-phase microextraction
      fiber. The molecularly imprinted polymer-coated solid-phase microextraction fiber
      was characterized by scanning electron microscopy and thermogravimetric analysis.
      Various parameters were investigated, including extraction temperature,
      extraction time, and desorption time. Under the optimum extraction conditions,
      the molecularly imprinted polymer-coated solid-phase microextraction fiber
      exhibited higher selectivity with greater extraction capacity toward parabens
      compared with the nonimprinted polymer-coated solid-phase microextraction fiber
      and commercial fibers. The molecularly imprinted polymer-coated solid-phase
      microextraction fiber was tested using gas chromatography to determine parabens,
      including methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, and propyl p
      hydroxybenzoate. The linear ranges were 0.01-10 MUg/mL with a correlation
      coefficient above 0.9943. The detection limits (under signal-to-noise ratio of 3)
      were below 0.30 MUg/L. The fiber was successfully applied to the simultaneous
      analysis of three parabens in spiked soy samples with satisfactory recoveries of
      95.48, 97.86, and 92.17%, respectively. The relative standard deviations (n=6)
      were within 2.83-3.91%. The proposed molecularly imprinted polymer-coated solid
      phase microextraction method is suitable for selective extraction and
      determination of trace parabens in food samples. 

PMID- 22162511
TI  - Obesity and metabolic syndrome in adolescent survivors of standard risk childhood
      acute lymphoblastic leukemia in Saudi Arabia.
AB  - BACKGROUND: This study estimated prevalence of unhealthy weight status and
      metabolic syndrome (MS) amongst Saudi survivors of standard risk ALL. PROCEDURE:
      We recruited 56 survivors, mean age 13.4 years (SD 4.1), a mean of 9.1 years (SD
      4.1) post-diagnosis. The BMI for age was used to define weight status relative to
      national (Saudi) and international (Cole et al., Cole-IOTF, WHO, and CDC)
      reference data. We measured body composition by dual-energy X-ray absorptiometry
      (DXA), waist circumference, blood pressure, lipid profile (HDL-C, Triglycerides),
      fasting glucose and insulin. RESULTS: According to international definitions
      based on BMI for age, around half of the sample had unhealthy weight status. All
      of the approaches based on BMI for age underestimated overfatness, present in
      27/51 (53%) of the sample according to DXA. Prevalence of MS was 7.1% (3/42 of
      those over 9-years old) and 5.4% (3/56) by applying the International Diabetes
      Federation (IDF) definition and National Cholesterol Education Program Third
      Adult Treatment panel Guidelines (NCEP III), respectively. However, MS by the
      NCEP III definition was present in 19% of the overweight and obese survivors and
      7.1% of the sample had at least two of the components of MS. CONCLUSION:
      Unhealthy body weight and overfatness may be common amongst adolescent Saudi
      survivors of standard risk ALL, though overweight and obesity may be no more
      common than in the general Saudi adolescent population. Defining weight status
      using BMI underestimates overfatness. Ideally, body composition and
      cardiometabolic risk factors should be monitored at late effects clinics.

PMID- 22162513
TI  - Combustion synthesis of blue-emitting submicron CaAl4O7:Eu2+, Dy3+ persistence
      phosphor.
AB  - Long persistence phosphor CaAl4O7:Eu(2+), Dy(3+) were prepared by a combustion
      method. The phosphors were characterized by means of X-ray diffraction (XRD),
      scanning electron microscopy (SEM), decay time measurement techniques and
      photoluminescence spectra (PL). The CaAl4O7:Eu(2+), Dy(3+) phosphor showed a
      broad blue emission, peaking at 445 nm when excited at 341 nm. Such a blue
      emission can be attributed to the intrinsic 4f -> 5d transitions of Eu(2+) in the
      host lattices. The lifetime decay curve of the Dy(3+) co-doped CaAl4O7:Eu(2+)
      phosphor contains a fast decay component and another slow decay one. Surface
      morphology also has been studied by SEM. The calculated CIE colour chromaticity
      coordinates was (0.227, 043). We have also discussed a possible long-persistent
      mechanism of CaAl4O7:Eu(2+), Dy(3+) phosphor. All the results indicate that this
      phosphor has promising potential for practical applications in the field of long
      lasting phosphors for the purposes of sign boards and defence.

PMID- 22162514
TI  - Regional differences in the evolution of lung disease in children with cystic
      fibrosis.
AB  - Progression of lung disease is a major event in children with cystic fibrosis
      (CF), but regional differences in its evolution are unclear. We hypothesized that
      regional differences occur beginning in early childhood. We examined this issue
      by evaluating 132 patients followed in the Wisconsin Neonatal Screening Project
      between 1985 and 2010. We scored chest X-rays obtained every 1-2 years with the
      Wisconsin chest X-ray system, in which we divided the lungs into quadrants, and
      gave special attention to ratings for bronchiectasis (BX) and nodular/branching
      opacities. We compared the upper and lower quadrant scores, and upper right and
      left quadrant scores, as patients aged using a multivariable generalized
      estimation equation (GEE) model. We did a confirmatory analysis for a subset of
      81 patients with chest computerized tomography (CT) images obtained in 2000 and
      scored using the Brody scoring system. The chest X-ray analysis shows that the
      upper quadrants have higher BX (P<0.001) and nodular/branching opacities
      (P<0.001) scores than the lower quadrants. CT analysis likewise reveals that the
      upper quadrants have more BX (P=0.02). Patients positive for mucoid PA showed
      significantly higher BX scores than patients with non-mucoid PA (P=0.001). Chest
      X-ray scoring also revealed that the upper right quadrant has more BX (P<0.001)
      than the upper left quadrant, and CT analysis was again confirmatory (P<0.001).
      We conclude that pediatric patients with CF develop more severe lung disease in
      the upper lobes than the lower lobes in association with mucoid PA infections and
      also have more severe lung disease on the right side than on the left side in the
      upper quadrants. A variety of potential explanations such as aspiration episodes
      may be clinically relevant and provide insights regarding therapies.

PMID- 22162515
TI  - Immortalization of bone marrow-derived porcine mesenchymal stem cells and their
      differentiation into cells expressing cardiac phenotypic markers.
AB  - Mesenchymal stem cells (MSCs) may be among the first stem cell types to be
      utilized in the clinic for cell therapy, because of their ease of isolation and
      extensive differentiation potential. Using a porcine model, we have established
      several cell lines from MSCs to facilitate in vitro and in vivo studies of their
      potential use for cellular therapy. Bone marrow-derived primary MSCs were
      immortalized using the pRNS-1 plasmid. We obtained four stable immortalized cell
      lines that exhibited higher proliferative capacities than the parental cells. All
      four cell lines displayed a common phenotype similar to that of primary
      mesenchymal cells, characterized by constitutively high expressions of CD90,
      CD29, CD44, SLA I and CD46, while CD172a, CD106 and CD56 were less expressed.
      Remarkably, treatment with 5-azacytidine-stimulated porcine MSCs lines to
      differentiate into cells that were positive for cardiac phenotypic markers, such
      as alpha-actin, connexin-43, sarcomeric actin, serca-2 and, to a lesser extent,
      desmin and troponin-T. These porcine MSC lines will be valuable biological tools
      for developing strategies for ex vivo expansion and differentiation of MSCs into
      a specific lineage.

PMID- 22162516
TI  - Screening for depression and risk of suicide in patients with arthritis: comment
      on the article by Tektonidou et al.

PMID- 22162517
TI  - Rat homologues to the human post-neonatal period: models for vulnerability to the
      sudden infant death syndrome.

PMID- 22162519
TI  - Pediatric asthma guidelines: what are they good for? A view from the "pro" side.

PMID- 22162518
TI  - Pregnancy in women diagnosed with antineutrophil cytoplasmic antibody-associated
      vasculitis: outcome for the mother and the child.
AB  - OBJECTIVE: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is
      infrequently seen in women of childbearing age. Only a limited number of
      pregnancies in women with AAV have been reported, and often they were associated
      with complications. METHODS: This was a single-center retrospective observational
      study. All pregnancies in women with granulomatosis with polyangiitis (Wegener's)
      (n = 13) and microscopic polyangiitis (n = 1) were included. Women of
      childbearing age were counseled to abstain from pregnancy during or shortly after
      disease activity or <1 year after cyclophosphamide treatment. RESULTS: We
      described 22 pregnancies in 14 women with AAV (median age at diagnosis was 25
      years [range 19-36 years]) diagnosed between 1982-2008. The ear, nose, and throat
      region (71%) and kidneys (50%) were predominantly involved. All women were in
      remission at conception and cyclophosphamide had been administered to 9 women (15
      pregnancies). The median gestational age was 39+4 weeks, including 2 preterm
      deliveries. The median birth weight was 3,400 gm (1,860-3,890 gm). Hypothyroidism
      occurred in 1 newborn and a cleft palate in 1 newborn of a twin pregnancy.
      Otherwise, the fetal outcome was excellent. Preeclampsia was diagnosed in 2
      pregnancies. A caesarean section was performed in 2 patients. The median followup
      after the last conception was 98 months (range 11-307 months). Eight women
      experienced a relapse 21 months (range 7-62 months) after conception, 1 during
      pregnancy, and 7 after delivery. CONCLUSION: In this study, the pregnancy outcome
      in patients with AAV in remission was excellent. Pregnancy in women with AAV in
      remission does not seem to be associated with increased risk of relapse.
      Counseling, careful management, and close followup are essential in pregnant
      women with AAV.

PMID- 22162520
TI  - Clinical manufacturing of recombinant human interleukin 15. I. Production cell
      line development and protein expression in E. coli with stop codon optimization.
AB  - Interleukin 15 (IL-15) has shown remarkable biological properties of promoting NK
      and T-cell activation and proliferation, as well as enhancing antitumor immunity
      of CD8(+) T cells in preclinical models. Here, we report the development of an E.
      coli cell line to express recombinant human Interleukin-15 (rhIL-15) for clinical
      manufacturing. Human IL-15 cDNA sequence was inserted into a pET28b plasmid and
      expressed in several E. coli BL21 strains. Through product quality comparisons
      among several E. coli strains, including E. coli BL21(DE3), BL21(DE3)pLysS,
      BLR(DE3)pLysS, and BL21-AI, E. coli BL21-AI was selected for clinical
      manufacturing. Expression optimization was carried out at shake flask and 20-L
      fermenter scales, and the product was expressed as inclusion bodies that were
      solubilized, refolded, and purified to yield active rhIL-15. Stop codons of the
      expression construct were further investigated after 15-20% of the purified rhIL
      15 showed an extraneous peak corresponding to an extra tryptophan residue based
      on peptide mapping and mass spectrometry analysis. It was determined that the
      presence of an extra tryptophan was due to a stop codon wobble effect, which
      could be eliminated by replacing TGA (opal) stop codon with TAA (ochre). As a
      novel strategy, a simple method of demonstrating lack of tRNA suppressors in the
      production host cells was developed to validate the cells in this study. The E.
      coli BL21-AI cells containing the rhIL-15 coding sequence with a triplet stop
      codon TAATAATGA were banked for further clinical manufacturing.

PMID- 22162521
TI  - Evaluating bronchodilator effects in chronic obstructive pulmonary disease using
      diffusion-weighted hyperpolarized helium-3 magnetic resonance imaging.
AB  - The objective of this study was to evaluate the regional effects of
      bronchodilator administration in chronic obstructive pulmonary disease (COPD)
      using hyperpolarized helium-3 ((3)He) MRI apparent diffusion coefficient (ADC).
      Ten COPD ex-smokers provided written, informed consent and underwent diffusion
      weighted, hyperpolarized (3)He MRI, spirometry, and plethysmography before and 25
      +/- 2 min after bronchodilator administration. Pre- and postsalbutamol whole-lung
      (WL) ADC maps were generated and registered together to identify the lung regions
      containing the (3)He signal at both time points, and mean ADC within those
      regions of interest (ROI) was determined for a measurement of previously
      ventilated ROI ADC (ADC(P)). Lung ROI with (3)He signal at both time points was
      used as a binary mask on postsalbutamol WL ADC maps to obtain an ADC measurement
      for newly ventilated ROI (ADC(N)). Postsalbutamol, no significant differences
      were detected in WL ADC (P = 0.516). There were no significant differences
      between ADC(N) and ADC(P) postsalbutamol (P = 1.00), suggesting that the ADC(N)
      lung regions were not more emphysematous than the lung ROI participating in
      ventilation before bronchodilator administration. Postsalbutamol, a statistically
      significant decrease in ADC(P) (P = 0.01) was detected, and there were
      significant differences between ADC(P) in the most anterior and most posterior
      image slices (P = 0.02), suggesting a reduction in regional gas trapping
      following bronchodilator administration. Regional evaluation of tissue
      microstructure using hyperpolarized (3)He MRI ADC provides insights into lung
      alterations that accompany improvements in regional (3)He gas distribution after
      bronchodilator administration.

PMID- 22162522
TI  - Micron-sized intrapulmonary particle deposition in the developing rat lung.
AB  - Little is known about the effects of postnatal developmental changes in lung
      architecture and breathing patterns on intrapulmonary particle deposition. We
      measured deposition in the developing Wistar-Kyoto rat, whose lung development
      largely parallels that of humans. Deposition of 2-MUm sebacate particles was
      determined in anesthetized, intubated, spontaneously breathing rats on postnatal
      days (P) 7 to 90 by aerosol photometry (Karrasch S, Eder G, Bolle I, Tsuda A,
      Schulz H. J Appl Physiol 107: 1293-1299, 2009). Respiratory parameters were
      determined by body plethysmography. Tidal volume increased substantially from P7
      (0.19 ml) to P90 (2.1 ml) while respiratory rate declined from 182 to 107/min.
      Breath-specific deposition was lowest (9%) at P7 and P90 and markedly higher at
      P35 (almost 16%). Structural changes of the alveolar region include a ninefold
      increase in surface area (Bolle I, Eder G, Takenaka S, Ganguly K, Karrasch S,
      Zeller C, Neuner M, Kreyling WG, Tsuda A, Schulz H. J Appl Physiol 104: 1167
      1176, 2008). Particle deposition per unit of time and surface area peaked at P35
      and showed a minimum at P90. At an inhaled particle number concentration of
      10(5)/cm(3), there was an estimated 450, 690, and 330 particles/(min * cm(2)) at
      P7, P35, and P90, respectively. Multiple regression models showed that deposition
      depends on the mean linear intercept as structural component and the breathing
      parameters, tidal volume, and respiratory rate (r(2) > 0.9). In conclusion,
      micron-sized particle deposition was dependent on the stage of postnatal lung
      development. A maximum was observed during late alveolarization (P35), which
      corresponds to human lungs of about eight years of age. Children at this age may
      therefore be more susceptible to micron-sized airborne environmental health
      hazards.

PMID- 22162523
TI  - The influence of respiratory acid-base changes on muscle performance and
      excitability of the sarcolemma during strenuous intermittent hand grip exercise.
AB  - Acidification has been reported to provide protective effects on force production
      in vitro. Thus, in this study, we tested if respiratory acid-base changes
      influence muscle function and excitability in vivo. Nine subjects performed
      strenuous, intermittent hand grip exercises (10 cycles of 15 s of work/45 s of
      rest) under respiratory acidosis by CO(2) rebreathing, alkalosis by
      hyperventilation, or control. The Pco(2), pH, K(+) concentration ([K(+)]), and
      Na(+) concentration were measured in venous and arterialized blood. Compound
      action potentials (M-wave) were elicited to examine the excitability of the
      sarcolemma. The surface electromyogram (EMG) was recorded to estimate the central
      drive to the muscle. The lowest venous pH during the exercise period was 7.24 +/-
      0.03 in controls, 7.31 +/- 0.05 with alkalosis, and 7.17 +/- 0.04 with acidosis
      (P < 0.001). The venous [K(+)] rose to similar maximum values in all conditions
      (6.2 +/- 0.8 mmol/l). The acidification reduced the decline in contraction speed
      (P < 0.001) but decreased the M-wave area to 73.4 +/- 19.8% (P < 0.001) of the
      initial value. After the first exercise cycle, the M-wave area was smaller with
      acidosis than with alkalosis, and, after the second cycle, it was smaller with
      acidosis than with the control condition (P < 0.001). The duration of the M-wave
      was not affected. Acidification diminished the reduction in performance, although
      the M-wave area during exercise was decreased. Respiratory alkalosis stabilized
      the M-wave area without influencing performance. Thus, we did not find a direct
      link between performance and alteration of excitability of the sarcolemma due to
      changes in pH in vivo.

PMID- 22162524
TI  - Training-induced adaptation in purine metabolism in high-level sprinters vs.
      triathletes.
AB  - The aim of this study was to assess the effect of training loads on metabolic
      response of purine derivatives in highly trained sprinters (10 men, age range 20
      29 yr) in a 1-yr cycle, compared with endurance-training mode in triathletes (10
      men, age range 21-28 yr). A four-time measurement of respiratory parameters,
      plasma hypoxanthine (Hx) concentration, and erythrocyte hypoxanthine-guanine
      phosphoribosyl transferase (HGPRT) activity was administered in four
      characteristic training phases (general, specific, competition, and transition).
      A considerably lower postexercise plasma concentration of Hx in sprinters (8.1
      18.0 MUmol/l) than in triathletes (14.1-24.9 MUmol/l) was demonstrated in all
      training phases. In both groups, a significant decrease in plasma Hx
      concentration in the competition phase and a considerable increase in the
      transition phase were observed. It was found that the resting erythrocyte HGPRT
      activity increased in the competition period and declined in the transition
      phase. Sprinters showed higher HGPRT activity (58.5-71.8 nmol IMP.mg Hb(-1).h(
      1)) than triathletes (55.8-66.6 nmol IMP.mg Hb(-1).h(-1)) in all examinations.
      The results suggest a more effective use of anaerobic metabolic energy sources
      induced by sprint training characterized by higher amount of exercise in the
      anaerobic lactacid and the nonlactacid zone. The changes in plasma Hx
      concentration and erythrocyte HGPRT activity might serve as sensitive metabolic
      indicators in the training control, especially in sprint-trained athletes. These
      parameters may provide information about the energetic status of the muscles in
      highly trained athletes in which no significant adaptation changes are detected
      by means of commonly acknowledged biochemical and physiological parameters.

PMID- 22162525
TI  - Effects of ambient pressure on pulmonary nitric oxide.
AB  - Airway nitric oxide (NO) has been proposed to play a role in the development of
      high-altitude pulmonary edema. We undertook a study of the effects of acute
      changes of ambient pressure on exhaled and alveolar NO in the range 0.5-4
      atmospheres absolute (ATA, 379-3,040 mmHg) in eight healthy subjects breathing
      normoxic nitrogen-oxygen mixtures. On the basis of previous work with inhalation
      of low-density helium-oxygen gas, we expected facilitated backdiffusion and
      lowered exhaled NO at 0.5 ATA and the opposite at 4 ATA. Instead, the exhaled NO
      partial pressure (Pe(NO)) did not differ between pressures and averaged 1.21 +/-
      0.16 (SE) mPa across pressures. As a consequence, exhaled NO fractions varied
      inversely with pressure. Alveolar estimates of the NO partial pressure differed
      between pressures and averaged 88 (P = 0.04) and 176 (P = 0.009) percent of
      control (1 ATA) at 0.5 and 4 ATA, respectively. The airway contribution to
      exhaled NO was reduced to 79% of control (P = 0.009) at 4 ATA. Our finding of the
      same Pe(NO) at 0.5 and 1 ATA is at variance with previous findings of a reduced
      Pe(NO) with inhalation of low-density gas at normal pressure, and this
      discrepancy may be due to the much longer durations of low-density gas breathing
      in the present study compared with previous studies with helium-oxygen breathing.
      The present data are compatible with the notion of an enhanced convective
      backtransport of NO, compensating for attenuated backdiffusion of NO with
      increasing pressure. An alternative interpretation is a pressure-induced
      suppression of NO formation in the airways.

PMID- 22162526
TI  - Differential effects of jump versus running exercise on trabecular architecture
      during remobilization after suspension-induced osteopenia in growing rats.
AB  - High-impact exercise is considered to be very beneficial for bones. We
      investigated the ability of jump exercise to restore bone mass and structure
      after the deterioration induced by tail suspension in growing rats and made
      comparisons with treadmill running exercise. Five-week-old male Wistar rats (n =
      28) were randomly assigned to four body weight-matched groups: a spontaneous
      recovery group after tail suspension (n = 7), a jump exercise group after tail
      suspension (n = 7), a treadmill running group after tail suspension (n = 7), and
      age-matched controls without tail suspension or exercise (n = 7). Treadmill
      running was performed at 25 m/min, 1 h/day, 5 days/wk. The jump exercise protocol
      consisted of 10 jumps/day, 5 days/wk, with a jump height of 40 cm. Bone mineral
      density (BMD) of the total right femur was measured by dual-energy X-ray
      absorptiometry. Three-dimensional trabecular bone architecture at the distal
      femoral metaphysis was evaluated using microcomputed tomography. After 5 wk of
      free remobilization, right femoral BMD, right hindlimb muscle weight, and body
      weight returned to age-matched control levels, but trabeculae remained thinner
      and less connected. Although both jump and running exercises during the
      remobilization period increased trabecular bone mass, jump exercise increased
      trabecular thickness, whereas running exercise increased trabecular number. These
      results indicate that restoration of trabecular bone architecture induced by jump
      exercise during remobilization is predominantly attributable to increased
      trabecular thickness, whereas running adds trabecular bone mass through
      increasing trabecular number, and suggest that jumping and running exercises have
      different mechanisms of action on structural characteristics of trabecular bone.

PMID- 22162527
TI  - Local tetrahydrobiopterin administration augments reflex cutaneous vasodilation
      through nitric oxide-dependent mechanisms in aged human skin.
AB  - Functional constitutive nitric oxide synthase (NOS) is required for full
      expression of reflex cutaneous vasodilation that is attenuated in aged skin. Both
      the essential cofactor tetrahydrobiopterin (BH(4)) and adequate substrate
      concentrations are necessary for the functional synthesis of nitric oxide (NO)
      through NOS, both of which are reduced in aged vasculature through increased
      oxidant stress and upregulated arginase, respectively. We hypothesized that acute
      local BH(4) administration or arginase inhibition would similarly augment reflex
      vasodilation in aged skin during passive whole body heat stress. Four intradermal
      microdialysis fibers were placed in the forearm skin of 11 young (22 +/- 1 yr)
      and 11 older (73 +/- 2 yr) men and women for local infusion of 1) lactated
      Ringer, 2) 10 mM BH(4), 3) 5 mM (S)-(2-boronoethyl)-l-cysteine + 5 mM N(omega)
      hydroxy-nor-l-arginine to inhibit arginase, and 4) 20 mM N(G)-nitro-l-arginine
      methyl ester (l-NAME) to inhibit NOS. Red cell flux was measured at each site by
      laser-Doppler flowmetry (LDF) as reflex vasodilation was induced. After a 1.0
      degrees C rise in oral temperature (T(or)), mean body temperature was clamped and
      20 mM l-NAME was perfused at each site. Cutaneous vascular conductance was
      calculated (CVC = LDF/mean arterial pressure) and expressed as a percentage of
      maximum (%CVC(max); 28 mM sodium nitroprusside and local heat, 43 degrees C).
      Vasodilation was attenuated at the control site of the older subjects compared
      with young beginning at a 0.3 degrees C rise in T(or). BH(4) and arginase
      inhibition both increased vasodilation in older (BH(4): 55 +/- 5%; arginase
      inhibited: 47 +/- 5% vs. control: 37 +/- 3%, both P < 0.01) but not young
      subjects compared with control (BH(4): 51 +/- 4%CVC(max); arginase-inhibited: 55
      +/- 4%CVC(max) vs. control: 56 +/- 6%CVC(max), both P > 0.05) at a 1 degrees C
      rise in T(or). With a 1 degrees C rise in T(or), local BH(4) increased NO
      dependent vasodilation in the older (BH(4): 31.8 +/- 2.4%CVC(max) vs. control:
      11.7 +/- 2.0%CVC(max), P < 0.001) but not the young (BH(4): 23 +/- 4%CVC(max) vs.
      control: 21 +/- 4%CVC(max), P = 0.718) subject group. Together these data suggest
      that reduced BH(4) contributes to attenuated vasodilation in aged human skin and
      that BH(4) NOS coupling mechanisms may be a potential therapeutic target for
      increasing skin blood flow during hyperthermia in older humans.

PMID- 22162528
TI  - Relationships between the lung clearance index and conductive and acinar
      ventilation heterogeneity.
AB  - The lung clearance index (LCI) derived from a multiple breath washout test has
      regained considerable popularity in recent years, alternatively being promoted as
      an early detection tool or a marker of small airways function. In this study, we
      systematically investigated the link between LCI and indexes of acinar and
      conductive airways ventilation heterogeneity (Sacin, Scond) to assess potential
      contributions from both lung zones. Relationships were examined in 55 normal
      subjects after provocation, where only Scond is known to be markedly increased,
      and in 55 asthma patients after bronchodilation, in whom both Scond and Sacin
      ranged between normal and abnormal. LCI was correlated to Scond in both groups (R
      = 0.37-0.43; P < 0.01 for both); in the asthma group, LCI was also tightly
      correlated to Sacin (R = 0.70; P < 0.001). Potential mechanisms operational at
      various levels of the bronchial tree were identified by considering washout
      curvilinearity in addition to LCI to distinguish specific ventilation and dead
      space effects (also illustrated by simple 2-compartment model simulations).
      Although the asthma data clearly demonstrate that LCI can reflect very peripheral
      ventilation heterogeneities, the normal provocation data also convincingly show
      that LCI increases may be the exclusive result of far more proximal ventilation
      heterogeneities. Because LCI potentially includes heterogeneities at all length
      scales, it is suggested that ventilation imaging in combination with LCI
      measurement at the mouth could identify the scale of relevant ventilation
      heterogeneities. In the meantime, interpretations of LCI results in the clinic
      based on washout curves collected at the mouth should be handled with caution.

PMID- 22162530
TI  - Amelia Earhart, alveolar mechanics, and other great mysteries.

PMID- 22162529
TI  - Increased shelterin mRNA expression in peripheral blood mononuclear cells and
      skeletal muscle following an ultra-long-distance running event.
AB  - Located at the end of chromosomes, telomeres are progressively shortened with
      each replication of DNA during aging. Integral to the regulation of telomere
      length is a group of proteins making up the shelterin complex, whose tissue
      specific function during physiological stress is not well understood. In this
      study, we examine the mRNA and protein levels of proteins within and associated
      with the shelterin complex in subjects (n = 8, mean age = 44 yr) who completed a
      physiological stress of seven marathons in 7 days. Twenty-two to 24 h after the
      last marathon, subjects had increased mRNA levels of DNA repair enzymes Ku70 and
      Ku80 (P < 0.05) in both skeletal muscle and peripheral blood mononuclear cells
      (PBMCs). Additionally, the PBMCs displayed an increment in three shelterin
      protein mRNA levels (TRF1, TRF2, and Pot-1, P < 0.05) following the event. Seven
      days of ultrarunning did not result in changes in mean telomere length,
      telomerase activity, hTert mRNA, or hterc mRNAs found in PBMCs. Higher protein
      concentrations of TRF2 were found in skeletal muscle vs. PBMCs at rest. Mean
      telomere length in skeletal muscle did not change and did not contain detectable
      levels of htert mRNA or telomerase activity. Furthermore, changes in the PBMCs
      could not be attributed to changes in the proportion of subtypes of CD4(+) or
      CD8(+) cells. We have provided the first evidence that, in humans, proteins
      within and associated with the shelterin complex increase at the mRNA level in
      response to a physiological stress differentially in PBMCs and skeletal muscle.

PMID- 22162531
TI  - Diameter-dependent axial prestretch of porcine coronary arteries and veins.
AB  - The pressure-diameter relation (PDR) and the wall strain of coronary blood
      vessels have important implications for coronary blood flow and arthrosclerosis,
      respectively. Previous studies have shown that these mechanical quantities are
      significantly affected by the axial stretch of the vessels. The objective of this
      study was to measure the physiological axial stretch in the coronary vasculature;
      i.e., from left anterior descending (LAD) artery tree to coronary sinus vein and
      to determine its effect on the PDR and hence wall stiffness. Silicone elastomer
      was perfused through the LAD artery and coronary sinus trees to cast the vessels
      at the physiologic pressure. The results show that the physiological axial
      stretch exists for orders 4 to 11 (> 24 MUm in diameter) arteries and orders -4
      to -12 (>38 MUm in diameter) veins but vanishes for the smaller vessels.
      Statistically, the axial stretch is higher for larger vessels and is higher for
      arteries than veins. The axial stretch lambda(z) shows a linear variation with
      the order number (n) as: lambda(z) = 0.062n + 0.75 (R(2) = 0.99) for artery and
      lambda(z) = -0.029n + 0.89 (R(2) = 0.99) for vein. The mechanical analysis shows
      that the axial stretch significantly affects the PDR of the larger vessels. The
      circumferential stretch/strain was found to be significantly higher for the
      epicardial arteries (orders 9-11), which are free of myocardium constraint, than
      the intramyocardial arteries (orders 4-8). These findings have fundamental
      implications for coronary blood vessel mechanics.

PMID- 22162532
TI  - Influence of CO2 on upper airway muscles and chest wall/diaphragm corticomotor
      responses assessed by transcranial magnetic stimulation in awake healthy
      subjects.
AB  - RATIONALE: Functional interaction between upper airway (UA) dilator muscles and
      the diaphragm is crucial in the maintenance of UA patency. This interaction could
      be altered by increasing respiratory drive. The aim of our study was to compare
      the effects of hypercapnic stimulation on diaphragm and genioglossus corticomotor
      responses to transcranial magnetic stimulation (TMS). METHODS: 10 self-reported
      healthy men (32 +/- 9 yr; body mass index = 24 +/- 3 kg/m(-2)) breathed, in
      random order, room air or 5% and then 7% Fi(CO(2)), both balanced with pure O(2).
      Assessments included ventilatory variables, isoflow UA resistance (at 300 ml/s),
      measurement of lower chest wall/diaphragm (LCW/diaphragm), and genioglossus motor
      threshold (MT) and motor-evoked potential (MEP) characteristics. TMS twitches
      were applied during early inspiration and end expiration at stimulation intensity
      30% above LCW/diaphragm and genioglossus MT. RESULTS: Compared with room air,
      CO(2) inhalation significantly augmented minute ventilation, maximal inspiratory
      flow, tidal volume, and tidal volume/respiratory time ratio. UA resistance was
      unchanged with CO(2) inhalation. During 7% CO(2) breathing, LCW/diaphragm MT
      decreased by 9.6 +/- 10.1% whereas genioglossus MT increased by 7.2 +/- 9%. CO(2)
      induced ventilatory stimulation led to elevation of LCW/diaphragm MEP amplitudes
      during inspiration but not during expiration. LCW/diaphragm MEP latencies
      remained unaltered both during inspiration and expiration. Genioglossus MEP
      latencies and amplitudes were unchanged with CO(2). CONCLUSION: In awake, healthy
      subjects, CO(2)-induced hyperventilation is associated with heightened
      LCW/diaphragm corticomotor activation without modulating genioglossus MEP
      responses. This imbalance may promote UA instability during increased respiratory
      drive.

PMID- 22162533
TI  - Population pharmacokinetic-pharmacodynamic analysis of istradefylline in patients
      with Parkinson disease.
AB  - This model-based analysis quantifies the population pharmacokinetic
      pharmacodynamic efficacy and safety/tolerability relationships of orally
      administered istradefylline, a selective adenosine A(2A) receptor antagonist, in
      healthy participants and patients with Parkinson disease. Data from 6 phase 2/3
      clinical trials comprised the population database, with 1760 and 1798 patients
      contributing to the efficacy and safety/tolerability analyses, respectively. The
      relationship between istradefylline area under the curve at steady state and
      percentage OFF time was described by a nonlinear model (Emax) based on time for
      the disease progression/placebo response component and an Emax model for the
      effect of istradefylline. The typical maximum decrease in percentage OFF time due
      to istradefylline exposure would be 5.79% (95% confidence interval = 4.09%-7.49%)
      with one-half of the maximum effect reached at an exposure of 1690 ng * hr/mL
      (95% confidence interval = 199-3180 ng * hr/mL). The pharmacokinetic
      pharmacodynamic relationships for dyskinesia and dizziness were described by an
      Emax model, and for nausea, a power model was used. The probabilities of
      dyskinesia and dizziness are expected to plateau at a dose of 40 mg/d, and the
      probability of nausea is expected to continually rise as the dose is increased.
      Collectively, these results support a starting istradefylline dose of 20 to 40
      mg/d.

PMID- 22162534
TI  - Multiple-dose safety, pharmacokinetics, and pharmacodynamics of the MU-opioid
      receptor inverse agonist GSK1521498.
AB  - The endogenous opioid system and u-opioid receptors in particular have been
      demonstrated to play a fundamental role in hedonic and motivational behaviors
      reinforced by rewards. In healthy participants, the authors examined the multiple
      dose safety, pharmacokinetic, and secondary pharmacodynamic profile of
      GSK1521498, a u-opioid receptor inverse agonist that is being developed for
      treatment of disorders of compulsive consumption. Clinically relevant doses of
      GSK1521498 (2, 5, and 10 mg) following once-daily administration for 10 days,
      were well tolerated with no clinically relevant changes in vital signs,
      chemistry, or hematologic parameters and with a favorable neuropsychiatric
      profile. Following oral administration, median first time to reach maximum
      observed plasma concentration for GSK1521498 occurred 2 to 5 hours after dosing,
      with individual values ranging from 1 to 8 hours. Systemic exposure to GSK1521498
      (area under the curve [0-infinity] and maximum observed plasma concentration)
      increased in a slightly greater-than-dose-proportional manner, and steady-state
      plasma levels were reached within approximately 7 days. The secondary
      pharmacodynamic effects of GSK1521498 on cognition and pain threshold and
      tolerance were dose related, with mild to moderate impairments in measures of
      attention and reductions of pressure pain threshold and tolerance at the highest
      dose. These findings provide encouraging safety, tolerability, and
      pharmacokinetic data in support of the continued clinical development of
      GSK1521498.

PMID- 22162535
TI  - Pharmacokinetics of the soluble guanylate cyclase activator cinaciguat in
      individuals with hepatic impairment.
AB  - Cinaciguat is intended for use in patients with acute decompensated heart
      failure. The drug is eliminated predominantly via the liver and, therefore, the
      potential impact of hepatic impairment on cinaciguat pharmacokinetics needs to be
      determined. This nonrandomized, open-label, observational study investigated the
      pharmacokinetics of cinaciguat in individuals with mild (Child-Pugh A; n = 8) or
      moderate (Child-Pugh B; n = 8) hepatic impairment and matched healthy volunteers
      (n = 16). An exploratory analysis of pharmacodynamic parameters was also
      conducted. Individuals with mild hepatic impairment and their controls received a
      single (4-hour) intravenous infusion of 100 ug/h cinaciguat, whereas individuals
      with moderate hepatic impairment and their controls received 50 ug/h. Cinaciguat
      was well tolerated and had a favorable safety profile. The most frequent
      treatment-emergent adverse events were headache (4 participants) and spontaneous
      penile erection (2 participants). In individuals with mild hepatic impairment,
      only minor increases in plasma cinaciguat concentrations and no significant
      differences in pharmacodynamic parameters were observed, compared with controls.
      Individuals with moderate hepatic impairment had a substantially higher
      cinaciguat exposure than controls. This higher exposure was associated with more
      pronounced vasodilatation. This study demonstrates that in individuals with mild
      hepatic impairment, individual dose adaptation may not be required.

PMID- 22162536
TI  - Suspected clonazepam-induced bullous dermatosis in a patient with respiratory
      failure.

PMID- 22162537
TI  - Clarification on precision criteria to derive sample size when designing
      pediatric pharmacokinetic studies.

PMID- 22162538
TI  - Population pharmacokinetic and pharmacodynamic model-based comparability
      assessment of a recombinant human Epoetin Alfa and the Biosimilar HX575.
AB  - The aim of this study was to develop an integrated pharmacokinetic and
      pharmacodynamic (PK/PD) model and assess the comparability between epoetin alfa
      HEXAL/Binocrit (HX575) and a comparator epoetin alfa by a model-based approach.
      PK/PD data-including serum drug concentrations, reticulocyte counts, red blood
      cells, and hemoglobin levels-were obtained from 2 clinical studies. In sum, 149
      healthy men received multiple intravenous or subcutaneous doses of HX575 (100
      IU/kg) and the comparator 3 times a week for 4 weeks. A population model based on
      pharmacodynamics-mediated drug disposition and cell maturation processes was used
      to characterize the PK/PD data for the 2 drugs. Simulations showed that due to
      target amount changes, total clearance may increase up to 2.4-fold as compared
      with the baseline. Further simulations suggested that once-weekly and thrice
      weekly subcutaneous dosing regimens would result in similar efficacy. The
      findings from the model-based analysis were consistent with previous results
      using the standard noncompartmental approach demonstrating PK/PD comparability
      between HX575 and comparator. However, due to complexity of the PK/PD model,
      control of random effects was not straightforward. Whereas population PK/PD model
      based analyses are suited for studying complex biological systems, such models
      have their limitations (statistical), and their comparability results should be
      interpreted carefully.

PMID- 22162539
TI  - Quantitative model of the relationship between dipeptidyl peptidase-4 (DPP-4)
      inhibition and response: meta-analysis of alogliptin, saxagliptin, sitagliptin,
      and vildagliptin efficacy results.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibition is a well- characterized treatment for
      type 2 diabetes mellitus (T2DM). The objective of this model-based meta-analysis
      was to describe the time course of HbA1c response after dosing with alogliptin
      (ALOG), saxagliptin (SAXA), sitagliptin (SITA), or vildagliptin (VILD). Publicly
      available data involving late-stage or marketed DPP-4 inhibitors were leveraged
      for the analysis. Nonlinear mixed-effects modeling was performed to describe the
      relationship between DPP-4 inhibition and mean response over time. Plots of the
      relationship between metrics of DPP-4 inhibition (ie, weighted average inhibition
      [WAI], time above 80% inhibition, and trough inhibition) and response after 12
      weeks of daily dosing were evaluated. The WAI was most closely related to
      outcome, although other metrics performed well. A model was constructed that
      included fixed effects for placebo and drug and random effects for intertrial
      variability and residual error. The relationship between WAI and outcome was
      nonlinear, with an increasing response up to 98% WAI. Response to DPP-4
      inhibitors could be described with a single drug effect. The WAI appears to be a
      useful index of DPP-4 inhibition related to HbA1c. Biomarker to response
      relationships informed by model-based meta-analysis can be leveraged to support
      study designs including optimization of dose, duration of therapy, and patient
      population.

PMID- 22162540
TI  - Food effect on bioavailability of modified-release trimetazidine tablets.
AB  - This study aimed to investigate a food effect on the bio-availability of modified
      release (MR) trimetazidine tablets in 36 healthy volunteers. Trimetazidine, an
      anti-ischemic drug, protects the myocardial cell from the harmful effects of
      ischemia. The authors investigated the effect of being under a fasting or fed
      state at the time of drug intake on the bioavailability of trimetazidine 35-mg MR
      tablets in a randomized, open-label, crossover, 2-arm, 4-period, 2-sequence
      bioequivalence study design with a 14-day washout period. Plasma concentration of
      trimetazidine was assayed in timed samples with a validated high- performance
      liquid chromatography/mass selective detector that had a lower limit of
      quantification of 2.5 ng/mL. Test and reference formulations gave a mean
      trimetazidine C(max) of 63.26 ng/mL and 69.18 ng/mL for the fasting state and
      64.19 ng/mL and 63.11 ng/mL for the fed state, respectively. The AUC(0-tlast)
      mean of trimetazidine was 726.31 ng.h/mL and 733.01 ng.h/mL for the fasting state
      and 706.40 ng.h/mL and 691.40 ng.h/mL for the fed state for test/reference
      formulations. There were no significant differences in pharmacokinetic parameters
      between the 2 formulations and the fasting/fed states. The authors showed that
      there is no food effect and no need for a 4-period study to evaluate the
      bioequivalence of trimetazidine MR tablets.

PMID- 22162541
TI  - Pharmacokinetics and pharmacodynamics of MK-5046, a bombesin receptor subtype-3
      (BRS-3) agonist, in healthy patients.
AB  - MK-5046 is an orally active, potent, selective agonist of the orphan G protein
      coupled receptor bombesin receptor subtype-3 (BRS-3) that is under evaluation for
      treatment of obesity. We report the safety, tolerability, pharmacokinetics, and
      pharmacodynamics of oral doses of MK-5046 (10-160 mg) in a double-blind,
      randomized, placebo-controlled study in healthy and obese male volunteers. MK
      5046 exposure increased dose proportionally, and MK-5046 was eliminated with an
      apparent terminal half-life of 1.5 to 3.5 hours. Single doses transiently
      increased blood pressure. Patients reported adverse events (erections and feeling
      hot, cold, and/or jittery) that coincided with time of occurrence (T(max)) and
      increased with increasing dose. No changes were observed in body temperature,
      heart rate, plasma glucose levels, or feelings of hunger/satiety. The blood
      pressure and thermal experiences attenuated with a second dose 6 hours after the
      first. Additionally, the erections suggest a possible, unanticipated, role for
      BRS-3 in reproductive physiology. Oral administration of MK-5046 achieves plasma
      concentrations that are projected to activate BRS-3 and therefore should be
      suitable for exploring its biological role in humans.

PMID- 22162542
TI  - Effect of telaprevir on the pharmacokinetics of midazolam and digoxin.
AB  - In this open-label study, 24 healthy volunteers received a single intravenous
      (IV) dose of 0.5 mg of midazolam on day 1 and a single oral dose each of 2 mg of
      midazolam and 0.5 mg of digoxin on day 3. Telaprevir 750 mg every 8 hours was
      administered from day 8 through day 23, along with a single IV dose of 0.5 mg of
      midazolam on day 17 and single oral doses of 2 mg of midazolam and 0.5 mg of
      digoxin on day 19. Midazolam, 1'-hydroxymidazolam, digoxin, and telaprevir
      concentrations in plasma and digoxin concentrations in urine were measured and
      pharmacokinetic parameters calculated. On comparing administration with versus
      without telaprevir, the geometric least squares mean ratios (with 90% confidence
      limits) for IV midazolam were 1.02 (0.80, 1.31) for maximum observed
      concentrations (C(max)) and 3.40 (3.04, 3.79) for area under the curve from 0 to
      24 hours (AUC(0-24h)); for oral midazolam 2.86 (2.52, 3.25) for C(max) and 8.96
      (7.75, 10.35) for AUC(0-24h); and for oral digoxin 1.50 (1.36, 1.65) for C(max)
      and 1.85 (1.70, 2.00) for area under the curve from 0 to infinity (AUC(0
      infinity)). Coadministration of telaprevir with oral midazolam resulted in
      approximately 3-fold decrease in the mean AUC(0-infinity) of 1'-hydroxymidazolam.
      The renal clearance of digoxin was similar with or without telaprevir. Results
      show that telaprevir is an inhibitor of CYP3A and P-glycoprotein.

PMID- 22162543
TI  - Possible laboratory contamination leads to incorrect reporting of Vibrio cholerae
      O1 and initiates an outbreak response.
AB  - Vibrio cholerae O1 in a river water specimen in South Africa was reported, and a
      public health response followed in order to prevent an outbreak. Further
      investigation determined this to be a pseudoalert of V. cholerae O1, possibly
      linked to laboratory contamination. Following culture of bacteria from the water
      specimen, the testing laboratory possibly contaminated the culture with a V.
      cholerae O1 reference strain and then mistakenly reported isolation of V.
      cholerae O1.

PMID- 22162544
TI  - Human leptospira isolates circulating in Mayotte (Indian Ocean) have unique
      serological and molecular features.
AB  - Leptospirosis is one of the most widespread zoonoses in the world. However, there
      is a lack of information on circulating Leptospira strains in remote parts of the
      world. We describe the serological and molecular features of leptospires isolated
      from 94 leptospirosis patients in Mayotte, a French department located in the
      Comoros archipelago, between 2007 and 2010. Multilocus sequence typing identified
      these isolates as Leptospira interrogans, L. kirschneri, L. borgpetersenii, and
      members of a previously undefined phylogenetic group. This group, consisting of
      15 strains, could represent a novel species. Serological typing revealed that 70%
      of the isolates belonged to the serogroup complex Mini/Sejroe/Hebdomadis,
      followed by the serogroups Pyrogenes, Grippotyphosa, and Pomona. However,
      unambiguous typing at the serovar level was not possible for most of the strains
      because the isolate could belong to more than one serovar or because serovar and
      species did not match the original classification. Our results indicate that the
      serovar and genotype distribution in Mayotte differs from what is observed in
      other regions, thus suggesting a high degree of diversity of circulating isolates
      worldwide. These results are essential for the improvement of current diagnostic
      tools and provide a starting point for a better understanding of the epidemiology
      of leptospirosis in this area of endemicity.

PMID- 22162545
TI  - Clostridium difficile carriage in elderly subjects and associated changes in the
      intestinal microbiota.
AB  - Clostridium difficile is an important nosocomial pathogen associated particularly
      with diarrheal disease in elderly individuals in hospitals and long-term care
      facilities. We examined the carriage rate of Clostridium difficile by culture as
      a function of fecal microbiota composition in elderly subjects recruited from the
      community, including outpatient, short-term respite, and long-term hospital stay
      subjects. The carriage rate ranged from 1.6% (n = 123) for subjects in the
      community, to 9.5% (n = 43) in outpatient settings, and increasing to 21% (n =
      151) for patients in short- or long-term care in hospital. The dominant 072
      ribotype was carried by 43% (12/28) of subjects, while the hypervirulent strain
      R027 (B1/NAP1/027) was isolated from 3 subjects (11%), 2 of whom displayed C.
      difficile associated diarrhea (CDAD) symptoms at the time of sampling. Emerging
      ribotypes with enhanced virulence (078 and 018) were also isolated from two
      asymptomatic subjects. Pyrosequencing of rRNA gene amplicons was used to
      determine the composition of the fecal microbiota as a surrogate for the
      microbial population structure of the distal intestine. Asymptomatic subjects (n
      = 20) from whom C. difficile was isolated showed no dramatic difference at the
      phylum or family taxonomic level compared to those that were culture negative (n
      = 252). However, in contrast, a marked reduction in microbial diversity at genus
      level was observed in patients who had been diagnosed with CDAD at the time of
      sampling and from whom C. difficile R027 was isolated.

PMID- 22162546
TI  - Effects of solid-medium type on routine identification of bacterial isolates by
      use of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) is a rapid method for the identification of bacteria. Factors that
      may alter protein profiles, including growth conditions and presence of exogenous
      substances, could hinder identification. Bacterial isolates identified by
      conventional methods were grown on various media and identified using the MALDI
      Biotyper (Bruker Daltonics, Billerica, MA) using a direct smear method and an
      acid extraction method. Specimens included 23 Pseudomonas isolates grown on blood
      agar, Pseudocel (CET), and MacConkey agar (MAC); 20 Staphylococcus isolates grown
      on blood agar, colistin-nalidixic acid agar (CNA), and mannitol salt agar (MSA);
      and 25 enteric isolates grown on blood agar, xylose lysine deoxycholate agar
      (XLD), Hektoen enteric agar (HE), salmonella-shigella agar (SS), and MAC. For
      Pseudomonas spp., the identification rate to genus using the direct method was
      83% from blood, 78% from MAC, and 94% from CET. For Staphylococcus isolates, the
      identification rate to genus using the direct method was 95% from blood, 75% from
      CNA, and 95% from MSA. For enteric isolates, the identification rate to genus
      using the direct method was 100% from blood, 100% from MAC, 100% from XLD, 92%
      from HE, and 87% from SS. Extraction enhanced identification rates. The direct
      method of MALDI-TOF analysis of bacteria from selective and differential media
      yields identifications of varied confidence. Notably, Staphylococci spp. from CNA
      exhibit low identification rates. Extraction enhances identification rates and is
      recommended for colonies from this medium.

PMID- 22162547
TI  - Hobi-like pestivirus in aborted bovine fetuses.
AB  - An outbreak of abortion affecting multiparous cows was associated with Hobi-like
      pestivirus infection. Viral RNA and antigens were detected in the tissues of two
      aborted fetuses. Molecular assays for other common abortogenic agents tested
      negative. At the genetic level, the Hobi-like pestivirus displayed the closest
      relatedness to Italian, Australian, and South American viruses, whereas it
      diverged from the prototype Thai isolate. These findings may have important
      implications for the pestivirus control/eradication programs in cattle herds.

PMID- 22162549
TI  - Comparison of the MALDI Biotyper system using Sepsityper specimen processing to
      routine microbiological methods for identification of bacteria from positive
      blood culture bottles.
AB  - Bloodstream infections are a leading cause of admissions to hospital intensive
      care units and carry a high mortality rate. Clinical outcome can be greatly
      improved by early effective antibiotic therapy; therefore, broad-spectrum
      antimicrobial therapy is often initiated when there is a clinical suspicion of
      bloodstream infection. Unfortunately, this method may not always be effective
      when dealing with inherently resistant organisms and can also result in
      iatrogenic infection and the development of resistant isolates. Rapid
      identification of the infecting organism may aid in choosing appropriate
      antimicrobial therapy, thereby reducing these potential adverse events. We
      compared the matrix-assisted laser desorption ionization (MALDI) Biotyper system
      with Sepsityper specimen processing (Bruker Daltonics, Billerica, MA) to routine
      methods for the identification of microorganisms from 164 positive blood
      cultures. The MALDI Biotyper/Sepsityper identified 85.5% of bacterial isolates
      directly from positive monomicrobial blood cultures with 97.6% concordance to
      genus and 94.1% concordance to species with routine identification methods. Gram
      negative isolates were more likely to produce acceptable confidence scores
      (97.8%) than gram-positive isolates (80.0%); however, genus and species
      concordance with routine identification methods were similar in both groups.
      Reanalysis of collected spectra using modified blood culture-specific parameters
      resulted in an improved overall identification rate for gram-positive bacteria
      (89.0%). Median times to identification using the MALDI Biotyper/Sepsityper were
      23 to 83 h faster than routine methods for gram-positive isolates and 34 to 51 h
      faster for gram-negative isolates.

PMID- 22162548
TI  - Rapid identification of mycobacteria and drug-resistant Mycobacterium
      tuberculosis by use of a single multiplex PCR and DNA sequencing.
AB  - Tuberculosis (TB) remains a significant global health problem for which rapid
      diagnosis is critical to both treatment and control. This report describes a
      multiplex PCR method, the Mycobacterial IDentification and Drug Resistance Screen
      (MID-DRS) assay, which allows identification of members of the Mycobacterium
      tuberculosis complex (MTBC) and the simultaneous amplification of targets for
      sequencing-based drug resistance screening of rifampin-resistant (rifampin(r)),
      isoniazid(r), and pyrazinamide(r) TB. Additionally, the same multiplex reaction
      amplifies a specific 16S rRNA gene target for rapid identification of M. avium
      complex (MAC) and a region of the heat shock protein 65 gene (hsp65) for further
      DNA sequencing-based confirmation or identification of other mycobacterial
      species. Comparison of preliminary results generated with MID-DRS versus culture
      based methods for a total of 188 bacterial isolates demonstrated MID-DRS
      sensitivity and specificity as 100% and 96.8% for MTBC identification; 100% and
      98.3% for MAC identification; 97.4% and 98.7% for rifampin(r) TB identification;
      60.6% and 100% for isoniazid(r) TB identification; and 75.0% and 98.1% for
      pyrazinamide(r) TB identification. The performance of the MID-DRS was also tested
      on acid-fast-bacterium (AFB)-positive clinical specimens, resulting in
      sensitivity and specificity of 100% and 78.6% for detection of MTBC and 100% and
      97.8% for detection of MAC. In conclusion, use of the MID-DRS reduces the time
      necessary for initial identification and drug resistance screening of TB
      specimens to as little as 2 days. Since all targets needed for completing the
      assay are included in a single PCR amplification step, assay costs, preparation
      time, and risks due to user errors are also reduced.

PMID- 22162550
TI  - Use of quantitative HIV RNA detection for early diagnosis of HIV infection in
      infants and acute HIV infections in Alberta, Canada.
AB  - Quantitative HIV RNA viral load (QVL) assays (Roche Diagnostics) were sensitive
      and specific when used to diagnose HIV infection in (i) HIV-exposed infants
      (sensitivity of 100% [63.1 to 100%] and specificity of 100% [97.9 to 100%]) and
      (ii) suspected acute HIV infection patients with a negative/indeterminate Western
      blot (sensitivity of 97.6% [91.6 to 99.7%] and specificity of 100% [96.1 to
      100%]). No false-positive QVL results were identified.

PMID- 22162551
TI  - Aerosolized vaccine as an unexpected source of false-positive Bordetella
      pertussis PCR results.
AB  - When 13 of 13 nasal wash specimens from a single pediatrician's office tested
      positive for low quantities of Bordetella pertussis DNA, we suspected
      prelaboratory contamination. Investigation revealed that Pentacel and Adacel
      vaccines contain high copy numbers of B. pertussis DNA, which can be aerosolized,
      causing false-positive B. pertussis PCR results.

PMID- 22162553
TI  - Multiplex real-time PCR assay and melting curve analysis for identifying
      Mycobacterium tuberculosis complex and nontuberculous mycobacteria.
AB  - A multiplex real-time PCR assay and melting curve analysis for identifying 23
      mycobacterial species was developed and evaluated using 77 reference strains and
      369 clinical isolates. Concordant results were obtained for all 189 (100%)
      isolates of the Mycobacterium tuberculosis complex and 169 (93.9%) isolates of
      nontuberculous mycobacteria. Our results showed that this multiplex real-time PCR
      assay is an effective tool for the mycobacterial identification from cultures.

PMID- 22162554
TI  - Pneumonia and bacteremia due to Kytococcus schroeteri.
AB  - Kytococcus schroeteri, a saprophyte of the human skin, may cause serious
      infections in the immunocompromised host. Here, we describe a case of pneumonia
      and bacteremia due to Kytococcus schroeteri in an immunocompromised patient,
      successfully treated with linezolid and trimethoprim-sulfamethoxazole.

PMID- 22162555
TI  - Molecular epidemiology over an 11-year period (2000 to 2010) of extended-spectrum
      beta-lactamase-producing Escherichia coli causing bacteremia in a centralized
      Canadian region.
AB  - A study was designed to assess the importance of sequence types among extended
      spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates causing
      bacteremia over an 11-year period (2000 to 2010) in a centralized Canadian
      region. A total of 197 patients with incident infections were identified; the
      majority presented with community-onset urosepsis, with a significant increase in
      the prevalence of ESBL-producing E. coli during the later part of the study. The
      majority of E. coli isolates produced either CTX-M-15 or CTX-M-14. We identified
      7 different major sequence types among 91% of isolates (i.e., the ST10 clonal
      complex, ST38, ST131, ST315, ST393, ST405, and ST648) and provided insight into
      their clinical and molecular characteristics. ST38 was the most antimicrobial
      susceptible sequence type and predominated during 2000 to 2004 but disappeared
      after 2008. ST131 was the most antimicrobial-resistant sequence type, and the
      influx of a single pulsotype of this sequence type was responsible for the
      significant increase of ESBL-producing E. coli strains since 2007. During 2010,
      49/63 (78%) of the ESBL-producing E. coli isolates belonged to ST131, and this
      sequence type had established itself as a major drug-resistant pathogen in
      Calgary, Alberta, Canada, posing an important new public health threat within our
      region. We urgently need well-designed epidemiological and molecular studies to
      understand the dynamics of transmission, risk factors, and reservoirs for E. coli
      ST131. This will provide insight into the emergence and spread of this
      multiresistant sequence type.

PMID- 22162556
TI  - Evaluation of any or type-specific persistence of high-risk human papillomavirus
      for detecting cervical precancer.
AB  - High-risk human papillomavirus (HR-HPV) testing is increasingly important. We
      therefore examined the impact on accuracy of repeated versus one-time testing,
      type-specific versus pooled detection, and assay analytic sensitivity. By using a
      nested case-control design from the ASCUS-LSIL Triage Study, we selected women
      with incident cervical intraepithelial neoplasia grade 2 or grade 3 (CIN2/3; n =
      325) and a random sample of women with <CIN2 as controls (n = 401). HPV DNA
      status was assessed using hybrid capture 2 (HC2), a pooled test for 13 HR-HPV
      types, and the linear array (LA) and the line blot assay (LBA), two PCR-based HPV
      genotyping assays, at enrollment and the 6-month follow-up visit. The relative
      sensitivity and specificity for different permutations of multiple measurements
      were compared to a single measurement using marginal regression models. We found
      that repeat detection of any HR-HPV (by HC2, LA, or LBA) and of type-specific
      persistence (by LA or LBA) were significantly more specific but less sensitive
      than use of a single time point measurement of any HR-HPV. Sensitivity decreased
      and specificity increased further when testing intervals were increased from 12
      to 24 months. Including detection of borderline carcinogenic/noncarcinogenic HPV
      types with HR-HPV types decreased specificity for repeat measures of HPV with no
      impact on sensitivity. Similar patterns were observed when we used a CIN3 end
      point. We conclude that assay performance for detecting incident CIN2/3 was
      affected by which types were included, the analytic sensitivity of the assay, and
      the testing interval. These trade-offs need to be considered when assessing the
      potential overall clinical utility of repeated testing for HR-HPV DNA to identify
      women at risk for CIN2/3.

PMID- 22162557
TI  - Next-generation sequencing of prostate tumors provides independent evidence of
      xenotropic murine leukemia virus-related gammaretrovirus contamination.

PMID- 22162552
TI  - Most HIV type 1 non-B infections in the Spanish cohort of antiretroviral
      treatment-naive HIV-infected patients (CoRIS) are due to recombinant viruses.
AB  - HIV-1 group M is classified into 9 subtypes, as well as recombinants favored by
      coinfection and superinfection events with different variants. Although HIV-1
      subtype B is predominant in Europe, intersubtype recombinants are increasing in
      prevalence and complexity. In this study, phylogenetic analyses of pol sequences
      were performed to detect the HIV-1 circulating and unique recombinant forms (CRFs
      and URFs, respectively) in a Spanish cohort of antiretroviral treatment-naive HIV
      infected patients included in the Research Network on HIV/AIDS (CoRIS).
      Bootscanning and other methods were used to define complex recombinants not
      assigned to any subtype or CRF. A total of 670 available HIV-1 pol sequences from
      different patients were collected, of which 588 (87.8%) were assigned to HIV-1
      subtype B and 82 (12.2%) to HIV-1 non-B variants. Recombinants caused the
      majority (71.9%) of HIV-1 non-B infections and were found in 8.8% of CoRIS
      patients. Eleven URFs (accounting for 13.4% of HIV-1 non-B infections),
      presenting complex mosaic patterns, were detected. Among them, 10 harbored
      subtype B fragments. Four of the 11 URFs were found in Spanish natives. A cluster
      of three B/CRF02_AG recombinants was detected. We conclude that complex variants,
      including unique recombinant forms, are being introduced into Spain through both
      immigrants and natives. An increase in the frequency of mosaic viruses,
      reflecting the increasing heterogeneity of the HIV epidemic in our country, is
      expected.

PMID- 22162558
TI  - Direct drug susceptibility testing of Mycobacterium tuberculosis for rapid
      detection of multidrug resistance using the Bactec MGIT 960 system: a multicenter
      study.
AB  - Conventional indirect drug susceptibility testing of Mycobacterium tuberculosis
      with liquid medium is well established and offers time-saving and reliable
      results. This multicenter study was carried out to evaluate if drug
      susceptibility testing (DST) can be successfully carried out directly from
      processed smear-positive specimens (direct DST) and if this approach could offer
      substantial time savings. Sputum specimens were digested, decontaminated, and
      concentrated by the laboratory routine procedure and were inoculated in Bactec
      MGIT 960 as well as Lowenstein-Jensen (LJ) medium for primary isolation. All the
      processed specimens which were acid-fast bacterium (AFB) smear positive were used
      for setting up direct DST for isoniazid (INH) and rifampin (RIF). After the
      antimicrobial mixture of polymyxin B, amphotericin B, nalidixic acid,
      trimethoprim, and azlocillin (PANTA) was added, the tubes were entered in the
      MGIT 960 instrument using the 21-day protocol (Bactec 960 pyrazinamide [PZA]
      protocol). Results obtained by direct DST were compared with those obtained by
      indirect DST to establish accuracy and time savings by this approach. Of a total
      of 360 AFB smear-positive sputum specimens set up for direct DST at four sites in
      three different countries, 307 (85%) specimens yielded reportable results.
      Average reporting time for direct DST was 11 days (range, 10 to 12 days). The
      average time savings by direct DST compared to indirect DST, which included time
      to isolate a culture and perform DST, was 8 days (range, 6 to 9 days). When
      results of direct DST were compared with those of indirect DST, there was 95.1%
      concordance with INH and 96.1% with rifampin. These findings indicate that direct
      DST with the Bactec MGIT 960 system offers further time savings and is a quick
      method to reliably detect multidrug resistance (MDR) cases.

PMID- 22162559
TI  - Emergence and continuous evolution of genotype 1E rubella viruses in China.
AB  - In China, rubella vaccination was introduced into the national immunization
      program in 2008, and a rubella epidemic occurred in the same year. In order to
      know whether changes in the genotypic distribution of rubella viruses have
      occurred in the postvaccination era, we investigate in detail the epidemiological
      profile of rubella in China and estimate the evolutionary rate, molecular clock
      phylogeny, and demographic history of the predominant rubella virus genotypes
      circulating in China using Bayesian Markov chain Monte Carlo phylodynamic
      analyses. 1E was found to be the predominant rubella virus genotype since its
      initial isolation in China in 2001, and no genotypic shift has occurred since
      then. The results suggest that the global 1E genotype may have diverged in 1995
      and that it has evolved at a mutation rate of 1.65 * 10(-3) per site per year.
      The Chinese 1E rubella virus isolates were grouped into either cluster 1 or
      cluster 2, which likely originated in 1997 and 2006, respectively. Cluster 1
      viruses were found in all provinces examined in this study and had a mutation
      rate of 1.90 * 10(-3) per site per year. The effective number of infections
      remained constant until 2007, and along with the introduction of rubella vaccine
      into the national immunization program, although the circulation of cluster 1
      viruses has not been interrupted, some viral lineages have disappeared, and the
      epidemic started a decline that led to a decrease in the effective population
      size. Cluster 2 viruses were found only in Hainan Province, likely because of
      importation.

PMID- 22162560
TI  - Clinical significance of quantifying Pneumocystis jirovecii DNA by using real
      time PCR in bronchoalveolar lavage fluid from immunocompromised patients.
AB  - Quantitative PCR (qPCR) is more sensitive than microscopy for detecting
      Pneumocystis jirovecii in bronchoalveolar lavage (BAL) fluid. We therefore
      developed a qPCR assay and compared the results with those of a routine
      immunofluorescence assay (IFA) and clinical data. The assay included automated
      DNA extraction, amplification of the mitochondrial large-subunit rRNA gene and an
      internal control, and quantification of copy numbers with the help of a plasmid
      clone. We studied 353 consecutive BAL fluids obtained for investigation of
      unexplained fever and/or pneumonia in 287 immunocompromised patients. No qPCR
      inhibition was observed. Seventeen (5%) samples were both IFA and qPCR positive,
      63 (18%) were IFA negative and qPCR positive, and 273 (77%) were both IFA and
      qPCR negative. The copy number was significantly higher for IFA-positive/qPCR
      positive samples than for IFA-negative/qPCR-positive samples (4.2 +/- 1.2 versus
      1.1 +/- 1.1 log(10) copies/MUl; P < 10(-4)). With IFA as the standard, the qPCR
      assay sensitivity was 100% for >=2.6 log(10) copies/MUl and the specificity was
      100% for >=4 log(10) copies/MUl. Since qPCR results were not available at the
      time of decision-making, these findings did not trigger cotrimoxazole therapy.
      Patients with systemic inflammatory diseases and IFA-negative/qPCR-positive BAL
      fluid had a worse 1-year survival rate than those with IFA-negative/qPCR-negative
      results (P < 10(-3)), in contrast with solid-organ transplant recipients (P =
      0.88) and patients with hematological malignancy (P = 0.26). Quantifying P.
      jirovecii DNA in BAL fluids independently of IFA positivity should be
      incorporated into the investigation of pneumonia in immunocompromised patients.
      The relevant threshold remains to be determined and may vary according to the
      underlying disease.

PMID- 22162561
TI  - Epidemiology and risk factors of community onset infections caused by extended
      spectrum beta-lactamase-producing Escherichia coli strains.
AB  - Limited clinical information is available regarding community onset infections
      caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. A
      case-control study was performed to evaluate the epidemiology and risk factors of
      these types of infections. A case patient was defined as a person whose clinical
      sample yielded ESBL-producing E. coli. For each case patient, one control was
      randomly chosen from a group of outpatients from whom non-ESBL-producing E. coli
      had been isolated and for whom a clinical sample had been sent to the same
      laboratory for culturing during the following week. Of 108 cases of ESBL
      producing E. coli, 56 (51.9%) were classified as health care associated (HCA).
      Univariate analysis showed male gender, HCA infection, severe underlying illness,
      and a prior receipt of antibiotics to be associated with ESBL-producing E. coli.
      In the multivariate analysis, HCA infection (odds ratio [OR], 3.18; 95%
      confidence interval [CI], 1.67 to 6.06; P < 0.001) and previous use of
      antibiotics (OR, 4.88; 95% CI, 2.08 to 11.48; P < 0.001) were found to be
      significantly associated with the ESBL group. In a multivariate analysis that
      included each antibiotic, previous use of fluoroquinolone (OR, 7.32; 95% CI, 1.58
      to 34.01; P = 0.011) was significantly associated with ESBL-producing E. coli. Of
      101 isolates in which ESBLs and their molecular relationships were studied, all
      isolates produced ESBLs from the CTX-M family (CTX-M-14, 40 isolates; CTX-M-15,
      39 isolates; and other members of the CTX-M family, 22 isolates). In conclusion,
      this study confirms that ESBL-producing E. coli strains are a notable cause of
      community onset infections in predisposed patients. HCA infection and previous
      use of fluoroquinolone were significant factors associated with ESBL-producing E.
      coli in community onset infections.

PMID- 22162562
TI  - Comparison of molecular typing methods useful for detecting clusters of
      Campylobacter jejuni and C. coli isolates through routine surveillance.
AB  - Campylobacter spp. may be responsible for unreported outbreaks of food-borne
      disease. The detection of these outbreaks is made more difficult by the fact that
      appropriate methods for detecting clusters of Campylobacter have not been well
      defined. We have compared the characteristics of five molecular typing methods on
      Campylobacter jejuni and C. coli isolates obtained from human and nonhuman
      sources during sentinel site surveillance during a 3-year period. Comparative
      genomic fingerprinting (CGF) appears to be one of the optimal methods for the
      detection of clusters of cases, and it could be supplemented by the sequencing of
      the flaA gene short variable region (flaA SVR sequence typing), with or without
      subsequent multilocus sequence typing (MLST). Different methods may be optimal
      for uncovering different aspects of source attribution. Finally, the use of
      several different molecular typing or analysis methods for comparing individuals
      within a population reveals much more about that population than a single method.
      Similarly, comparing several different typing methods reveals a great deal about
      differences in how the methods group individuals within the population.

PMID- 22162563
TI  - Strong correlation between liver and serum levels of hepatitis C virus core
      antigen and RNA in chronically infected patients.
AB  - HCV core antigen (Ag) and HCV RNA levels were evaluated in matched liver biopsy
      samples and sera from 22 patients with hepatitis C infection by using the
      quantitative Architect HCV Ag immunoassay and a real-time RT-qPCR assay,
      respectively. The data showed a strong correlation between liver and serum
      compartments of HCV Ag levels (r = 0.80) and HCV RNA levels (r = 0.87). In
      summary, the serum HCV Ag and RNA levels reflect the intrahepatic values.

PMID- 22162564
TI  - Effectiveness of an integrated real-time PCR method for detection of the
      Mycobacterium tuberculosis complex in smear-negative extrapulmonary samples in an
      area of low tuberculosis prevalence.
AB  - Early extrapulmonary tuberculosis (EPTB) diagnosis is particularly difficult.
      Among 108 smear-negative extrapulmonary samples showing a positive culture for
      Mycobacterium tuberculosis complex (43 body fluids and 65 nonliquid specimens),
      63 (58.3%) were positive with the Xpert MTB/RIF assay (GX). GX sensitivity was
      quite low for samples from sterile locations (especially for pleural fluids:
      26.9%) but high for some nonliquid samples, like abscess aspirates (76.5%). In
      summary, GX may be a useful tool to be considered for EPTB diagnosis.

PMID- 22162565
TI  - Obesity and breast cancer outcome: adding to the evidence.

PMID- 22162566
TI  - Congenital anomalies in the children of cancer survivors: a report from the
      childhood cancer survivor study.
AB  - PURPOSE: Children with cancer receive mutagenic treatments, which raises concern
      about the potential transmissibility of germline damage to their offspring. This
      question has been inadequately studied to date because of a lack of detailed
      individual treatment exposure assessment such as gonadal radiation doses.
      METHODS: Within the Childhood Cancer Survivor Study, we performed a retrospective
      cohort analysis of validated cases of congenital anomalies among 4,699 children
      of 1,128 male and 1,627 female childhood cancer survivors. We quantified
      chemotherapy with alkylating agents and radiotherapy doses to the testes and
      ovaries and related these exposures to risk of congenital anomalies using
      logistic regression. RESULTS: One hundred twenty-nine children had at least one
      anomaly (prevalence = 2.7%). For children whose mothers were exposed to radiation
      or alkylating agents versus neither, the prevalence of anomalies was 3.0% versus
      3.5% (P = .51); corresponding figures were 1.9% versus 1.7% (P = .79) for the
      children of male survivors. Neither ovarian radiation dose (mean, 1.19 Gy; odds
      ratio [OR] = 0.59; 95% CI, 0.20 to 1.75 for 2.50+ Gy) nor testicular radiation
      dose (mean, 0.48 Gy; OR = 1.01; 95% CI, 0.36 to 2.83 for 0.50+ Gy) was related to
      risk of congenital anomalies. Treatment with alkylating agents also was not
      significantly associated with anomalies in the children of male or female
      survivors. CONCLUSION: Our findings offer strong evidence that the children of
      cancer survivors are not at significantly increased risk for congenital anomalies
      stemming from their parent's exposure to mutagenic cancer treatments. This
      information is important for counseling cancer survivors planning to have
      children.

PMID- 22162567
TI  - Adiponectin: a risk biomarker and attractive target for chemoprevention.

PMID- 22162568
TI  - Insulin- and obesity-related variables in early-stage breast cancer: correlations
      and time course of prognostic associations.
AB  - PURPOSE: To investigate patterns of prognostic associations over time of insulin-
      and obesity-related variables measured at diagnosis of early breast cancer (BC),
      focusing on whether the prognostic associations with distant recurrence and death
      changed over time. PATIENTS AND METHODS: Five hundred thirty-five nondiabetic
      women with T1-3, N0-1, M0 invasive BC diagnosed from 1989 to 1996 were included
      in the study. Insulin-related variables included fasting insulin, Homeostasis
      Model Assessment, C-peptide, and glucose. Obesity-related variables included
      weight, body mass index (BMI), waist and hip circumference, and leptin.
      Correlations were examined using the Pearson correlation coefficient and
      prognostic associations using the Cox model. RESULTS: There was evidence that
      associations of baseline insulin-related variables with distant recurrence and
      death were not constant over time; univariable adverse prognostic associations
      were significant only during the first 5 years (eg, insulin quartile 4 v 1:
      hazard ratio [HR], 2.32; 95% CI, 1.39 to 3.86; P < .001 for distant disease-free
      survival [DDFS]; and HR, 2.85; 95% CI, 1.48 to 5.50; P = .002 for overall
      survival [OS], with little attenuation of this pattern in multivariable
      analyses). In contrast, obesity-related variables (BMI, weight, leptin) exerted
      significant adverse univariable associations that were constant over time (eg,
      BMI quartile 4 v 2: HR, 1.40; 95% CI, 1.07 to 1.82 for DDFS; P = .014; and HR,
      1.50; 95% CI, 1.16 to 1.93; P < .001 for OS); prognostic associations of leptin
      remained significant in multivariable analyses. CONCLUSION: Baseline insulin- and
      obesity-related variables exert different patterns of prognostic associations
      over time in early BC.

PMID- 22162569
TI  - Completing the Arc: targeted inhibition of RET in medullary thyroid cancer.

PMID- 22162571
TI  - Evidence does not support clinically significant lenalidomide-CCI-779 interaction
      via P-glycoprotein.

PMID- 22162570
TI  - Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a
      pooled analysis of north central cancer treatment group phase III trials N9741
      and N9841.
AB  - PURPOSE: Symptoms and complications of metastatic colorectal cancer (mCRC) differ
      by metastatic sites. There is a paucity of prospective survival data for patients
      with peritoneal carcinomatosis colorectal cancer (pcCRC). We characterized
      outcomes of patients with pcCRC enrolled onto two prospective randomized trials
      of chemotherapy and contrasted that with other manifestations of mCRC (non
      pcCRC). METHODS: A total of 2,095 patients enrolled onto two prospective
      randomized trials were evaluated for overall survival (OS) and progression-free
      survival (PFS). A Cox proportional hazard model was used to assess the adjusted
      associations. RESULTS: The characteristics of the pcCRC group (n = 364) were
      similar to those of the non-pcCRC patients in median age (63 v 61 years, P =
      .23), sex (57% males v 61%, P = .23), and performance status (Eastern Cooperative
      Oncology Group performance status 0 or 1 94% v 96%, P = .06), but differed in
      frequency of liver (63% v 82%, P < .001) and lung metastases (27% v 34%, P =
      .01). Median OS (12.7 v 17.6 months, hazard ratio [HR] = 1.3; 95% CI, 1.2 to 1.5;
      P < .001) and PFS (5.8 v 7.2 months, HR = 1.2; 95% CI, 1.1 to 1.3; P = .001) were
      shorter for pcCRC versus non-pcCRC. The unfavorable prognostic influence of pcCRC
      remained after adjusting for age, PS, liver metastases, and other factors (OS: HR
      = 1.3, P < .001; PFS: HR = 1.1, P = .02). Infusional fluorouracil, leucovorin,
      and oxaliplatin was superior to irinotecan, leucovorin, and fluorouracil as a
      first-line treatment among pcCRC (HR for OS = 0.62, P = .005) and non-pcCRC
      patients (HR = 0.66, P < .001). CONCLUSION: pcCRC is associated with a
      significantly shorter OS and PFS as compared with other manifestations of mCRC.
      Future trials for mCRC should consider stratifying on the basis of pcCRC status.

PMID- 22162572
TI  - Cerebral sinus thrombosis and leptomeningeal carcinomatosis in a patient with
      ovarian cancer.

PMID- 22162573
TI  - Rapid radiographic and clinical improvement after treatment of a MET-amplified
      recurrent glioblastoma with a mesenchymal-epithelial transition inhibitor.

PMID- 22162574
TI  - The challenge and promise of the genomic era.

PMID- 22162576
TI  - Pain in the butt: marginal zone lymphoma of the gluteus muscle.

PMID- 22162578
TI  - Listening: reflections on a series of counseling sessions.

PMID- 22162575
TI  - Randomized phase II/III trial assessing gemcitabine/carboplatin and
      methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer
      who are unfit for cisplatin-based chemotherapy: EORTC study 30986.
AB  - PURPOSE: This is the first randomized phase II/III trial comparing two
      carboplatin-based chemotherapy regimens in patients with urothelial cancer who
      are ineligible ("unfit") for cisplatin chemotherapy. PATIENTS AND METHODS: The
      primary objective of the phase III part of this study was to compare the overall
      survival (OS) of chemotherapy-naive patients with measurable disease and an
      impaired renal function (glomerular filtration rate < 60 but > 30 mL/min) and/or
      performance score of 2 who were randomly assigned to receive either
      gemcitabine/carboplatin (GC) or methotrexate/carboplatin/vinblastine (M-CAVI). To
      detect an increase of 50% in median survival with GC compared with M-CAVI (13.5 v
      9 months) based on a two-sided log-rank test at error rates alpha = .05 and beta
      = .20, 225 patients were required. Secondary end points were overall response
      rate (ORR), progression-free survival (PFS), toxicity, and quality of life.
      RESULTS: In all, 238 patients were randomly assigned by 29 institutions over a
      period of 7 years. The median follow-up was 4.5 years. Best ORRs were 41.2%
      (36.1% confirmed response) for patients receiving GC versus 30.3% (21.0%
      confirmed response) for patients receiving M-CAVI (P = .08). Median OS was 9.3
      months in the GC arm and 8.1 months in the M-CAVI arm (P = .64). There was no
      difference in PFS (P = .78) between the two arms. Severe acute toxicity (death,
      grade 4 thrombocytopenia with bleeding, grade 3 or 4 renal toxicity, neutropenic
      fever, or mucositis) was observed in 9.3% of patients receiving GC and 21.2% of
      patients receiving M-CAVI. CONCLUSION: There were no significant differences in
      efficacy between the two treatment groups. The incidence of severe acute
      toxicities was higher for those receiving M-CAVI.

PMID- 22162579
TI  - Acute leukemic manifestation of recurrent anaplastic large-cell lymphoma 20 years
      after autologous bone marrow transplantation.

PMID- 22162577
TI  - Prognostic effect of circulating adiponectin in a randomized 2 x 2 trial of low
      dose tamoxifen and fenretinide in premenopausal women at risk for breast cancer.
AB  - PURPOSE: Adipokines are linked to obesity and insulin sensitivity and have
      recently been related to breast cancer risk and prognosis. We investigated the
      associations of plasma leptin and adiponectin with mammographic density and
      disease status and assessed their prognostic effect on recurrence-free survival
      in premenopausal women at risk for breast cancer. PATIENTS AND METHODS: We
      measured circulating lipids, insulin-like growth factor 1, glucose, insulin and
      insulin sensitivity (calculated by homeostasis model assessment [HOMA] index),
      leptin, adiponectin, and leptin-to-adiponectin ratio in 235 premenopausal women
      with pT1mic/pT1a breast cancer (n = 21), intraepithelial neoplasia (n = 160), or
      5-year Gail risk of 1.3% or greater (n = 54) who participated in a 2 * 2 trial of
      low-dose tamoxifen, fenretinide, both agents, or placebo over a 2-year period.
      RESULTS: At baseline, adiponectin levels were directly associated with
      mammographic density and HDL cholesterol and negatively associated with leptin,
      leptin-to-adiponectin ratio, body mass index (BMI), and HOMA index. Median
      adiponectin levels were lower in affected than in unaffected women (P = .006).
      After a median of 7.2 years and total of 57 breast neoplastic events, there was a
      12% reduction in the risk of breast neoplastic events per unit increase of
      adiponectin (adjusted hazard ratio, 0.88; 95% CI, 0.81 to 0.96; P = .03). There
      was no interaction between treatment and adiponectin levels. CONCLUSION: Low
      adiponectin levels are associated with a history of prior intraepithelial
      neoplasia or pT1mic/pT1a breast cancer and higher risk of second breast
      neoplastic events in premenopausal women. The associations are independent of
      BMI, mammographic density, and treatment. Our findings support the role of
      adiponectin as a potential target for premenopausal breast cancer prevention and
      treatment.

PMID- 22162580
TI  - Major response to everolimus in melanoma with acquired imatinib resistance.

PMID- 22162581
TI  - Unusual adverse event with vandetanib in metastatic medullary thyroid cancer.

PMID- 22162582
TI  - Phosphatidylinositide-3-kinase inhibitors: addressing questions of isoform
      selectivity and pharmacodynamic/predictive biomarkers in early clinical trials.

PMID- 22162583
TI  - Consistency in the analysis and reporting of primary end points in oncology
      randomized controlled trials from registration to publication: a systematic
      review.
AB  - PURPOSE: To improve the quality of reporting of randomized clinical trials
      (RCTs), international registries for RCTs and guidelines for primary end point
      (PEP) analysis were established. The objectives of this systematic review were to
      evaluate concordance of PEP between publication and the corresponding registry
      and to assess intrapublication consistency in PEP reporting. METHODS: All adult
      oncology RCTs in solid tumors published in 10 journals between 2005 and 2009 were
      reviewed. Registration information was extracted from international trial
      registries. RESULTS: A total 366 RCTs were identified. Trial registration was
      found for 215 trials, and the rate increased from 43% in 2005 to 82% in 2009 (P <
      .001). There were 134 RCTs with clearly defined PEPs in registry, with the rate
      increasing from 15% to 67% (P < .001). PEP differed between registration and
      final publication in 14% trials with clearly defined PEPs. Reporting issues in
      methodology were found in 15% of RCTs, mainly because of inadequate reporting of
      PEP or sample size calculation. Problems with the interpretation of trial results
      were found in 22% publications, mostly resulting from negative superiority
      studies being interpreted as showing equivalence. CONCLUSION: The rates of trial
      registration and of trials with clearly defined PEPs have improved over time;
      however, 14% of these trials reported a different PEP in the final publication.
      Intrapublication inconsistencies in PEP reporting are frequent. Our findings
      highlight the need for investigators, peer reviewers, and readers to exercise
      increased awareness and scrutiny of reporting outcomes of oncology RCTs.

PMID- 22162584
TI  - Familial aggregation of acute myeloid leukemia and myelodysplastic syndromes.
AB  - PURPOSE: Apart from rare pedigrees with multiple cases of acute myeloid leukemia
      (AML), there is limited data on familial aggregation of AML and myelodysplastic
      syndromes (MDSs) in the population. PATIENTS AND METHODS: Swedish population
      based registry data were used to evaluate risk of AML, MDS, and other
      malignancies among 24,573 first-degree relatives of 6,962 patients with AML and
      1,388 patients with MDS compared with 106,224 first-degree relatives of matched
      controls. We used a marginal survival model to calculate familial aggregation.
      RESULTS: AML and/or MDS did not aggregate significantly in relatives of patients
      with AML. There was a modest risk ratio (RR, 1.3; 95% CI, 0.9 to 1.8) in
      myeloproliferative/myeloid malignancies combined. The risks for any hematologic
      or any solid tumor were modestly but significantly increased. Relatives of
      patients with MDS did not show an increased risk for any hematologic tumors. In
      contrast, we found a significantly increased risk (RR, 6.5; 95% CI, 1.1 to 38.0)
      of AML/MDS and of all myeloid malignancies combined (RR, 3.1; 95% CI, 1.0 to 9.8)
      among relatives of patients diagnosed at younger than age 21 years. CONCLUSION:
      We did not find evidence for familial aggregation of the severe end of the
      spectrum of myeloid malignancies (AML and MDS). The risks of myeloproliferative
      neoplasms were modestly increased with trends toward significance, suggesting a
      possible role of inheritance. In contrast, although limited in sample size,
      relatives of young patients with AML were at increased risk of AML/MDS,
      suggesting that germline genes may play a stronger role in these patients. The
      increased risk of all hematologic malignancies and of solid tumors among
      relatives of patients with AML suggests that genes for malignancy in general
      and/or other environmental factors may be shared.

PMID- 22162585
TI  - Breast cancer survivors' perceptions of survivorship care options.
AB  - PURPOSE: As the number of breast cancer survivors increases, a durable model of
      comprehensive survivor care is needed, incorporating providers and/or visit types
      both within and outside of oncology. The objective of this study was to explore
      survivors' comfort with different clinician types or with a telephone/Internet
      based virtual visit as components of survivorship care. METHODS: Breast cancer
      survivors participating in a general survivorship survey completed an additional
      breast cancer-specific questionnaire evaluating the self-perceived impact of
      follow-up visits to various clinician types, or follow-up by a virtual visit, on
      survival, worrying, and stress related to cancer. RESULTS: A total of 218 breast
      cancer survivors completed the questionnaire. Most favored medical oncologist
      follow-up visits over those with primary care physicians (PCPs) or nurse
      practitioners (NPs) in terms of reduced worrying about cancer (odds ratio [OR],
      2.21; P < .001), reduced stress around the visit (OR, 1.40; P = .002), and
      improved effect on cancer survival (OR, 2.38; P < .001). However, the majority
      also displayed substantial comfort with both PCPs and NPs in the same domains.
      Patients rated a virtual visit as having a less favorable impact on cancer
      survival and cancer-related worrying compared with in-person visits with
      clinicians. CONCLUSION: Breast cancer survivors are comfortable with both PCPs
      and NPs providing follow-up care, although they indicate a preference for medical
      oncologists. Given patients' negative impressions of a virtual visit, increased
      familiarity with and research investigating this emerging concept are needed. The
      NP-led survivorship clinic model, with increased guidance for PCPs, offers a
      promising route for improving quality of and satisfaction with survivor care.

PMID- 22162586
TI  - Spontaneous regression of follicular dendritic cell sarcoma.

PMID- 22162587
TI  - Evolution of clinical trials registries.

PMID- 22162588
TI  - Does cancer treatment in childhood induce transgenerational genetic damage?

PMID- 22162589
TI  - Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in
      patients with advanced solid tumors.
AB  - PURPOSE: This phase I dose-escalation study investigated the maximum-tolerated
      dose (MTD), safety, preliminary activity, pharmacokinetics (PK), and
      pharmacodynamics of BKM120, a potent and highly specific oral pan-Class I PI3K
      inhibitor. PATIENTS AND METHODS: Thirty-five patients with advanced solid tumors
      received daily BKM120 12.5 to 150 mg. Dose escalation was guided by a Bayesian
      logistic regression model with overdose control. Assessments included archival
      tumor molecular status, response by Response Evaluation Criteria in Solid Tumors
      (RECIST), positron emission tomography tracer uptake ([(18)F]fluorodeoxyglucose
      positron emission tomography [FDG-PET]), fasting plasma C-peptide, and
      phosphorylated ribosomal protein S6 (pS6) in skin biopsies. RESULTS: Overall,
      treatment was well tolerated. Dose-limiting toxicities were grade 2 mood
      alteration (80 mg), grade 3 epigastralgia, grade 3 rash, grade 2 and grade 3 mood
      alteration (100 mg), and two grade 4 hyperglycemia (150 mg). The MTD was 100
      mg/d. Frequent treatment-related adverse events included rash, hyperglycemia,
      diarrhea, anorexia, and mood alteration (37% each); nausea (31%); fatigue (26%);
      pruritus (23%); and mucositis (23%). BKM120 demonstrated rapid absorption, half
      life of ~40 hours, ~three-fold steady-state accumulation, dose-proportional
      exposure, and moderate interpatient variability. One patient demonstrated a
      confirmed partial response (triple-negative breast cancer); seven patients (20%)
      were on study for >= 8 months. BKM120 demonstrated dose-dependent pharmacodynamic
      effects on [(18)F]FDG-PET, fasting C-peptide, fasting blood glucose, and pS6. No
      significant trends were seen to correlate tumor molecular alterations with
      clinical activity. CONCLUSION: This study demonstrates feasibility and proof-of
      concept of class I PI3K inhibition in patients with advanced cancers. BKM120, at
      the MTD of 100 mg/d, is safe and well tolerated, with a favorable PK profile,
      clear evidence of target inhibition, and preliminary antitumor activity.

PMID- 22162590
TI  - Interim [18F]fluorodeoxyglucose positron emission tomography scan in diffuse
      large B-cell lymphoma treated with anthracycline-based chemotherapy plus
      rituximab.
AB  - PURPOSE: The prognostic value of [(18)F]fluorodeoxyglucose-positron emission
      tomography (PET), interpreted according to visual criteria, is a matter of debate
      for diffuse large B-cell lymphoma (DLBCL). Moreover, most published studies do
      not differentiate between patients treated with or without rituximab. We
      retrospectively investigated the prognostic value of PET performed in patients
      with DLBCL receiving chemotherapy plus rituximab. Images were interpreted both
      visually and by computing maximum standardized uptake value (SUV(max)) between
      PET performed at baseline and after two cycles of chemotherapy. PATIENTS AND
      METHODS: One hundred twelve patients newly diagnosed with DLBCL were treated with
      an anthracycline-based regimen plus rituximab. A PET was performed after two
      cycles of treatment. PET positivity or negativity was related to progression-free
      survival (PFS) and overall survival (OS) using Kaplan-Meier analysis. RESULTS:
      Visual analysis showed that 70 patients (62.5%) presented with a negative PET
      scan after two cycles of treatment. The 3-year PFS and OS rates were 84% and 88%,
      respectively, in patients with PET-negative results versus 47% and 62%,
      respectively, in patients with PET-positive results (P < .0001 and P < .003,
      respectively). A second analysis was performed on 85 patients by using interim
      PET in a quantitative approach on the basis of a DeltaSUV(max) evaluation of more
      than 66%. The 3-year PFS was 77% for patients with PET-negative results and 37.5%
      for patients with PET-positive results (P = .002). CONCLUSION: An early PET scan
      after two cycles of treatment can effectively predict the outcome in patients
      with DLBCL treated with rituximab and anthracycline-based chemotherapy by using
      either a visual or quantitative approach.

PMID- 22162591
TI  - Factors dictating outcomes in patients with colorectal cancer and peritoneal
      carcinomatosis: selection, resection, or convection?

PMID- 22162592
TI  - Fatal infusion reactions to cetuximab: role of immunoglobulin e-mediated
      anaphylaxis.

PMID- 22162593
TI  - Scleromyxedema: a cutaneous paraneoplastic syndrome associated with thymic
      carcinoma.

PMID- 22162594
TI  - A Structural Evaluation of a Large-Scale Quasi-Experimental Microfinance
      Initiative.
AB  - This paper uses a structural model to understand, predict, and evaluate the
      impact of an exogenous microcredit intervention program, the Thai Million Baht
      Village Fund program. We model household decisions in the face of borrowing
      constraints, income uncertainty, and high-yield indivisible investment
      opportunities. After estimation of parameters using pre-program data, we evaluate
      the model's ability to predict and interpret the impact of the village fund
      intervention. Simulations from the model mirror the data in yielding a greater
      increase in consumption than credit, which is interpreted as evidence of credit
      constraints. A cost-benefit analysis using the model indicates that some
      households value the program much more than its per household cost, but overall
      the program costs 20 percent more than the sum of these benefits.

PMID- 22162595
TI  - Prevalence of comorbid conditions with aging among patients with diabetes and
      cardiovascular disease.
AB  - OBJECTIVES: The objectives were to develop a methodology to understand the
      prevalence of medically complex patients, and to apply the methodology to examine
      patients with one or more of hypertension, hyperlipidemia, diabetes, and heart
      disease. METHODS: Prevalence was measured using insurance data by calculating the
      proportion of days patients in a health state of interest contributed to the
      total days of enrollment. Graphs summarized the prevalence patterns within age
      and morbidity categories. Results by age and gender were supplemented with cubic
      spline curves that closely fit the prevalence data. RESULTS: The study provides
      basic epidemiologic information on changes with aging in the prevalence of
      patients with one or more comorbid conditions. Patients such as those with
      hyperlipidemia alone rose in prevalence at younger ages and fell at older ages,
      whereas the prevalence of other patients, such as patients having hypertension,
      diabetes, and heart disease, progressively increased with age. With
      straightforward extensions of the methodology other issues such as the incidence
      of emergency department visits and hospitalizations might be investigated.

PMID- 22162596
TI  - Barriers to healthcare of homeless residents of three Honolulu shelters.
AB  - In Honolulu, health insurance rates amongst the homeless are one of the highest
      in the nation, yet significant health care needs are still unmet. In a previous
      model, health care barriers have been divided into four domains: bureaucratic,
      personal, programmatic, and financial. This study aimed to determine the risk
      factors associated with the domains of health care barriers amongst the study's
      sample of 128 subjects across three Honolulu homeless shelters. Univariate models
      revealed health care barriers; but only the lack of health insurance was a
      significant financial barrier to health care in multivariate analyses (Odds
      ratio: 2.12; 95% Confidence Interval: 1.09-4.16). The identification of barriers
      should guide how health care programs approach Honolulu's homeless population to
      better serve their health care needs.

PMID- 22162597
TI  - Epidemiology of jellyfish stings presented to an American urban emergency
      department.
AB  - INTRODUCTION: Cnidarian, or jellyfish, stings are a common malady in tropical
      Emergency Departments. There are limited studies examining cnidarian stings in
      the United States. The team investigated the epidemiology and treatments for
      jellyfish stings presenting to an urban emergency department (ED) in Honolulu,
      Hawai'i. METHODS: The team performed a retrospective chart analysis of stings
      presented between 2000 and 2008. A total of 116 patients were identified. Charts
      were reviewed for patient demographics, incident characteristics, patient arrival
      condition, and treatments given in the emergency department. RESULTS: The median
      age was 24 years (range 9-85). Of patients 58% were men, 64% were Hawai'i non
      residents, and 23 % arrived between the hours of 10pm and 2 am. Emergency Medical
      System transported 64%, and 65% arrived with normal vital signs. Twenty-four
      different types of IV/PO medications were administered and patients received up
      to 5 different medications per visit. Intravenous medications were given to 64%.
      All patients were eventually discharged home from the ED. DISCUSSION: Risk
      factors for cnidarian stings include being men, being a Hawai'i non-resident, and
      nighttime ocean activities. Stings were treated with various medications and
      routes suggesting that there is no current standard of care for stings. This
      study suggests that there is a need for public health interventions tailored to
      tourists. Prevention and education of home treatment could decrease the cost of
      health care by decreasing ambulance transports and total number of ED visits for
      a non-urgent disease.

PMID- 22162598
TI  - Medical School Hotline: Tobacco dependence and the management of tobacco-related
      disorders: how John A. Burns School of Medicine is preparing our future
      physicians.

PMID- 22162599
TI  - UH Cancer Center Hotline: Recruiting cancer survivors for an online health
      behavior change intervention: are different strategies more beneficial?

PMID- 22162601
TI  - A report on the first case of vancomycin-intermediate Staphylococcus aureus
      (VISA) in Hawai'i.
AB  - The state of Hawai'i has the highest prevalence of methicillin-resistant
      Staphylococcus aureus (MRSA) infection in the United States. Since vancomycin is
      the most frequently-prescribed antibiotic for healthcare-associated MRSA
      infection, there is concern for development of vancomycin resistance. We report
      on a 61 year-old woman with history of previous successful treatments of MRSA
      bacteremia with vancomycin. She was later hospitalized for catheter-related MRSA
      bacteremia that persisted despite vancomycin treatment. The vancomycin minimal
      inhibitory concentration (MIC) was initially 1-2 ug/ml, suggesting
      susceptibility, but changed to 4 ug/ml. At this level, the organism was
      classified as a vancomycin-intermediate Staphylococcus aureus (VISA). Therapy was
      changed from vancomycin to daptomycin, and the patient's blood cultures were
      sterilized. High suspicion of VISA should be raised in MRSA-infected patients who
      fail or have a history of vancomycin therapy so that additional susceptibility
      testing and appropriate antibiotic therapy can be promptly commenced to reduce
      the morbidity associated with VISA infection.

PMID- 22162602
TI  - Pancreaticoduodenectomy in the setting of intestinal malrotation.
AB  - Malrotation is an intestinal gestational disorder which not only affects the
      positioning of the midgut, but also its vascular supply. While this is generally
      thought of as a pediatric surgical condition, it can have significant
      implications for adult surgeries as well. Herein we present a patient with
      asymptomatic nonrotation of the midgut with a concomitant pancreatic
      adenocarcinoma. The authors review the modifications necessary to perform a
      pancreaticoduodenectomy in a nonrotated patient. The review includes a caution
      and emphasis on an understanding of the vascular anatomic variants.

PMID- 22162603
TI  - Towards cultural competency in end-of-life communication training.
AB  - To meet the needs of a more diverse population, a culturally sensitive approach
      to end-of-life communication is critical. This paper describes a unique
      communication workshop that introduces future physicians to the delivery of
      culturally responsive care for patients in palliative and end-of-life treatment.
      The workshop is embedded within the required fourth year medical student rotation
      in Geriatrics and Palliative Care. Using case-vignettes, role playing, and small
      group discussions, content areas include: breaking bad news, discussing advanced
      directives, and decisions regarding withdrawal or withholding of treatment. Post
      workshop student evaluations reveal an overwhelmingly favorable response to the
      curriculum, with high scores for overall quality of the workshop, practical
      value, and appropriateness for level of training. This workshop meets the goal
      for all graduating medical students to engage in culturally competent palliative
      and end of life patient care.

PMID- 22162604
TI  - Celiac disease presenting as severe osteopenia.
AB  - The authors describe a unique presentation of celiac disease as multiple non
      traumatic fractures in a young male without gastrointestinal complaints. A 29
      year-old man presented with back pain and was found to have a non-traumatic
      compression fracture of the lumbar and thoracic spine on plain X-ray. Dual-energy
      x-ray absorptiometry (DXA) confirmed osteoporosis at the L3/L4 vertebral bodies.
      Parathyroid hormone (PTH), calcium, and vitamin D levels were normal. He had no
      gastrointestinal complaints, but serologic studies were positive to include an
      elevated gliadin IgA Ab, gliadin IgG Ab, and an elevated tissue transglutaminase
      IgA Ab. He was treated with a gluten-free diet, calcium, and vitamin D
      supplementation as well as teriparatide. Follow up bone density showed
      improvement and has no further fractures to date. Primary care physicians,
      gastroenterologists, and endocrinologists must have a high index of clinical
      suspicion for celiac disease in any patient who presents with low bone density
      regardless of the serum 25-OH vitamin D levels or presence of gastrointestinal
      complaints.

PMID- 22162605
TI  - Medical School Hotline: Turning the tragedy of tobacco around: how revenue from
      cigarettes improves health in Hawai'i.
AB  - JABSOM takes its responsibility to improve health among Hawai'i's people to
      heart. The school's vision is, ALOHA: to Attain Lasting Optimal Health for All, a
      theme adopted through a strategic planning process which engaged JABSOM's
      partners in the health and life sciences including its private sector
      collaborators and its sister colleges throughout the University of Hawai'i's ten
      campus system. JABSOM's ability to collaborate and contribute in these areas has
      been irrevocably enhanced by tobacco-related funding that the State of Hawai'i
      has committed to develop the Kaka'ako campus. The taxpayers' generosity has
      improved the education and reach of clinicians and researchers who, in turn,
      dedicate their lives to preventing, treating and eliminating the deadly grip
      tobacco holds on too many of the people of Hawai'i.

PMID- 22162607
TI  - Improving toxicology knowledge in preclinical medical students using high
      fidelity patient simulators.
AB  - BACKGROUND: Superior patient care and optimal physician training are often
      mutually elusive in the Emergency Department setting. Highfidelity patient
      simulators (HFPSs) are being used with increasing frequency in the training of
      medical students (MS) because they enable students to develop and refine medical
      competency in a non-threatening and safe environment. However, learner outcomes
      using HFPSs in this setting have not been well studied. OBJECTIVES: The objective
      of this pilot study was to determine the effectiveness of HFPSs in simulation
      (SIM) training as a learning tool for preclinical second-year MS to further
      increase their toxicology knowledge. METHODS: Second-year MS at a Problem Based
      Learning (PBL) medical school received a PBL toxicology teaching session in the
      middle of the semester. One week later, the students participated in a SIM
      exercise based on issues taken from the PBL case. The SIM exercise required that
      students address learning issues such as identifying abnormal findings, ordering
      tests, and, ultimately, initiating treatment on a full-scale HFPS mannequin. A
      supervised on-line test consisting of 10 multiple choice questions regarding the
      student's understanding of the learning issues was completed before the PBL class
      and directly before and after the SIM to determine the effectiveness of the HFPS
      use. Immediate video-assisted feedback was provided by emergency medicine
      attendings. RESULTS: Use of HFPSs during SIM exercises and in combination with
      PBL significantly increased toxicology knowledge in secondyear MS as determined
      by the improvement of on-line test scores (% correct answers) from 59% before PBL
      / before SIM to 69% after PBL / before SIM to 80% after PBL / after SIM.
      CONCLUSION: This study suggests that HFPS may be a valuable tool in helping to
      improve toxicology knowledge in second-year MS at a key transition period prior
      to beginning clerkship experiences. Incorporation of HFPS into PBL curricula may
      also be beneficial to MS in other areas of study where interactive learning could
      assist in evoking emotional realism while also enhancing critical thinking and
      acquisition of knowledge thereby facilitating the transition from theory to
      practice.

PMID- 22162608
TI  - Cost-benefit estimates of an elderly exercise program on Kaua'i.
AB  - The elderly consume a disproportionate amount of health care resources, and the
      recent trend in obesity will only escalate costs. EnhanceFitness(r) (EF) is an
      exercise program designed to increase the strength, flexibility, and balance of
      older adults. A comprehensive controlled study in Washington state of an elderly
      population has shown that participants who attend at least one EF class per week
      reduce healthcare costs by 20% per year. The present study reports the costs and
      potential benefits of replicating EF on Kaua'i. For Kaua'i the annual cost of an
      EF pilot program for 132 clients would be $204,735. Attendance records of the
      Kaua'i program showed that 96 (73%) of those enrolled attended at least weekly.
      Based on national reports of healthcare costs for the elderly, averting 20% of
      the costs for these 96 elderly would save $344,256 per year. The expected
      investment to return ratio, I-R ratio, for EF on Kaua'i is about 1-1.8. On
      economic grounds, a case can be made to support and expand these types of
      programs. In these times of budget cuts, cost-benefit analysis provides a common
      economic "language" to prioritize among different programs.

PMID- 22162609
TI  - Maggot debridement therapy in the treatment of complex diabetic wounds.
AB  - The growth and aging of the population of Hawai'i with a high incidence of
      diabetes mandates a need for more effective strategies to manage the healing of
      complicated wounds. Maggot debridement therapy (MDT) is one alternative utilized
      with successful results. Observations have indicated that maggots have the
      ability to debride wound beds, provide anti-microbial activity and also stimulate
      wound healing in diabetic patients. None of the patients refused MDT due to
      aversion of this treatment modality and the majority of patients had minimal
      discomfort. In 17 of 23 patients with multiple co-morbidities, the treatment of
      their complex diabetic wounds by MDT resulted in improvement or cure. Maggot
      debridement therapy is an effective treatment of diabetic wounds.

PMID- 22162610
TI  - Atypical presentations of methemoglobinemia from benzocaine spray.
AB  - Widely used for local anesthesia, especially prior to endoscopic procedures,
      benzocaine spray is one of the most common causes of iatrogenic
      methemoglobinemia. The authors report an atypical case of methemoglobinemia in a
      woman presenting with pale skin and severe hypoxemia, after a delayed repeat
      exposure to benzocaine spray. Early recognition and prompt management of
      methemoglobinemia is needed in order to lessen morbidity and mortality from this
      entity.

PMID- 22162611
TI  - Medical School Hotline: Developing communication skills for leading family
      meetings.
AB  - Good clinician-family communication is essential for the provision of high
      quality patient care. Families rate the communication skills of clinicians as
      critical clinical skills. However, there has been no structured training of
      fellow communication skills while leading family meetings in the University of
      Hawai'i Geriatric Medicine Fellowship Program. Effective training to develop
      communication skills with families will better prepare Geriatric Medicine fellows
      for this important task, and ultimately improve the quality of care they provide
      to these patients and patients' families.

PMID- 22162613
TI  - Faculty and resident perceptions regarding overnight student call during the
      third year OB/GYN clerkship.
AB  - OBJECTIVES: The objective of this study is to identify university faculty,
      community physician, and resident perceptions of how a schedule that employs
      overnight call in addition to a traditional weekday schedule affects medical
      student education, well being, and patient care during the third year obstetrics
      and gynecology clerkship. METHODS: In July 2007, a descriptive study was
      performed by distributing surveys to community teaching physicians, current
      residents, and faculty in the University of Hawai'i Department of Obstetrics and
      Gynecology. A total of 114 surveys were distributed to all current residents,
      clinical faculty and full-time faculty in the University of Hawai'i Department of
      Obstetrics and Gynecology. The survey included questions regarding the effect of
      the student call/work hour restrictions. RESULTS: A response rate of 45.6% was
      obtained (52/114). Results demonstrate that 84.6% (44/52) of residents, faculty,
      and community attendings agree that third year medical students should take call
      during their obstetrics and gynecology clerkship. Data was analyzed utilizing
      Spearman correlation and Cochran-Mantel-Haenszel statistics. No statistical
      difference was detected in terms of age or physician type (resident vs faculty vs
      community attending). CONCLUSION: Most physician-educators believe that medical
      students benefit from taking overnight call during their obstetrics and
      gynecology clerkship. Careful consideration should be given prior to elimination
      of overnight call in the obstetrics and gynecology clerkship.

PMID- 22162614
TI  - Emergence of community-acquired extended-spectrum beta-lactamase Escherichia coli
      (ESBLEC) in Honolulu: a case series of three individuals with community-acquired
      ESBLEC bacteriuria.
AB  - Community-acquired extended-spectrum beta-lactamase E coli (ESBLEC) have not been
      previously described in Honolulu. Its emergence as a community-acquired pathogen
      is concerning. This case series describes three patients who were diagnosed with
      community-acquired ESBLEC bacteriuria in 2010.

PMID- 22162615
TI  - Perceptions related to diet and exercise among Asians and Pacific Islanders with
      diabetes.
AB  - The purpose of this study was to explore the perceptions of Asians and Pacific
      Islanders (API) with Type 2 diabetes related to diet and exercise. A descriptive
      content analysis was conducted on verbalized responses from 15 participants in
      focus groups who were asked "What role does your culture play in what, when, and
      how much you eat?" and "If and/or how much you exercise and what type of exercise
      you do?" The participants recorded responses were transcribed verbatim and
      analyzed for themes utilizing the social ecological framework.The families,
      environment, and the local culture in Hawai'i greatly affect the dietary and
      physical activities of the participants. Psychosocial themes related to diet
      included depression, denial, and lack of self control. Physical activities were
      impacted by motivation and awareness of complications of diabetes. Family
      upbringing, social events, food portions and variety, and reciprocity contributed
      to eating behaviors of the participants. Family values in sports and role
      expectations of gender influenced physical activities.This study identified
      social ecological influences on health behavior among Asians and Pacific
      Islanders. The findings suggest various efforts for physicians and other health
      care providers to assist API in taking care of their diabetes.

PMID- 22162618
TI  - Much ado about religion: Religiosity, resource loss, and support for political
      violence.
AB  - The association between religion and violence has raised much interest in both
      academic and public circles. Yet on the individual level, existing empirical
      accounts are both sparse and conflicting. Based on previous research which found
      that religion plays a role in the support of political violence only through the
      mediation of objective and perceived deprivations, the authors test Conservation
      of Resource (COR) theory as an individual level explanation for the association
      of religion, socio-economic deprivations, and support for political violence. COR
      theory predicts that when individuals' personal, social or economic resources are
      threatened, a response mechanism may include violence. Utilizing two distinct
      datasets, and relying on structural equation models analysis, the latter two
      stages of a three-stage study are reported here. In a follow-up to their previous
      article, the authors refine the use of socio-economic variables in examining the
      effects of deprivation as mediating between religion and political violence.
      Then, they analyze an independent sample of 545 Muslims and Jews, collected
      during August and September 2004, to test a psychological-based explanation based
      on COR theory. This study replaces measures of deprivation used in the previous
      stages with measures of economic and psychological resource loss. Findings show
      that the relationship between religion and support of political violence only
      holds true when mediated by deprivations and psychological resource loss. They
      also suggest that the typical tendency to focus on economic resource loss is over
      simplistic as psychological, not economic, resources seem to mediate between
      religion and support of violence.

PMID- 22162619
TI  - Selective methoxy ether cleavage of 2,6-dimethoxyphenol followed by a selective
      acylation.
AB  - A Friedel-Crafts reaction of 2,6-dimethoxyphenol in the presence of aluminum
      chloride and propanoyl or butanoyl chlorid, respectively, lead, at elevated
      temperatures, to a selective cleavage of one of the methoxy groups followed by a
      selective acylation of the meta position with respect to the phenolic hydroxyl
      group. Under the same reaction conditions 2-methoxyphenol doesn't get
      demethylated; a mechanism to account for these findings is proposed. This
      reaction gives access to a variety of ortho-acylated catechols. Substituted
      catechols are widely used in supramolecular chemistry and are precursors of
      pesticides, flavors and fragrances. Additionally, catechol moieties are found in
      various natural products.

PMID- 22162620
TI  - Psychological Distress Following Suicidality Among Gay, Lesbian, and Bisexual
      Youths: Role of Social Relationships.
AB  - Longitudinal relations between past suicidality and subsequent changes in
      psychological distress at follow-up were examined among gay, lesbian, and
      bisexual (GLB) youths, as were psychosocial factors (e.g., self-esteem, social
      support, negative social relationships) that might mediate or moderate this
      relation. Past suicide attempters were found to have higher levels of depressive
      symptoms, anxious symptoms, and conduct problems at a later time than youths who
      neither attempted nor ideated. Psychosocial factors failed to mediate this
      relation. The interaction among past suicidality, social support, and negative
      relationships was associated with subsequent changes in all three psychological
      distress indicators six months later. Specifically, high levels of support
      (either from family or friends) or negative relationships were found to predict
      increased psychological distress among those with a history of suicide attempts,
      but not among youths without a history of suicidality. The findings suggest that
      GLB youths who attempt suicide continue to have elevated levels of psychological
      distress long after their attempt and they highlight the importance of social
      relationships in the youths' psychological distress at follow-up.

PMID- 22162621
TI  - Prediction with measurement errors in finite populations.
AB  - We address the problem of selecting the best linear unbiased predictor (BLUP) of
      the latent value (e.g., serum glucose fasting level) of sample subjects with
      heteroskedastic measurement errors. Using a simple example, we compare the usual
      mixed model BLUP to a similar predictor based on a mixed model framed in a finite
      population (FPMM) setup with two sources of variability, the first of which
      corresponds to simple random sampling and the second, to heteroskedastic
      measurement errors. Under this last approach, we show that when measurement
      errors are subject-specific, the BLUP shrinkage constants are based on a pooled
      measurement error variance as opposed to the individual ones generally considered
      for the usual mixed model BLUP. In contrast, when the heteroskedastic measurement
      errors are measurement condition-specific, the FPMM BLUP involves different
      shrinkage constants. We also show that in this setup, when measurement errors are
      subject-specific, the usual mixed model predictor is biased but has a smaller
      mean squared error than the FPMM BLUP which point to some difficulties in the
      interpretation of such predictors.

PMID- 22162622
TI  - For Richer, for Poorer: Money as a Topic of Marital Conflict in the Home.
AB  - Guided by a family stress perspective, we examined the hypothesis that discussing
      money would be associated with the handling of marital conflict in the home.
      Analyses were based on dyadic hierarchical linear modeling of 100 husbands' and
      100 wives' diary reports of 748 conflict instances. Contrary to findings from
      previous laboratory-based surveys, spouses did not rate money as the most
      frequent source of marital conflict in the home. However, compared to non-money
      issues, marital conflicts about money were more pervasive, problematic, and
      recurrent, and remained unresolved, despite including more attempts at problem
      solving. Implications for professionals who assist couples in managing their
      relationships and family finances are discussed.

PMID- 22162623
TI  - Next-generation sequencing facilitates quantitative analysis of wild-type and
      Nrl(-/-) retinal transcriptomes.
AB  - PURPOSE: Next-generation sequencing (NGS) has revolutionized systems-based
      analysis of cellular pathways. The goals of this study are to compare NGS-derived
      retinal transcriptome profiling (RNA-seq) to microarray and quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) methods and to evaluate
      protocols for optimal high-throughput data analysis. METHODS: Retinal mRNA
      profiles of 21-day-old wild-type (WT) and neural retina leucine zipper knockout
      (Nrl(-/-)) mice were generated by deep sequencing, in triplicate, using Illumina
      GAIIx. The sequence reads that passed quality filters were analyzed at the
      transcript isoform level with two methods: Burrows-Wheeler Aligner (BWA) followed
      by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT-PCR validation was
      performed using TaqMan and SYBR Green assays. RESULTS: Using an optimized data
      analysis workflow, we mapped about 30 million sequence reads per sample to the
      mouse genome (build mm9) and identified 16,014 transcripts in the retinas of WT
      and Nrl(-/-) mice with BWA workflow and 34,115 transcripts with TopHat workflow.
      RNA-seq data confirmed stable expression of 25 known housekeeping genes, and 12
      of these were validated with qRT-PCR. RNA-seq data had a linear relationship with
      qRT-PCR for more than four orders of magnitude and a goodness of fit (R(2)) of
      0.8798. Approximately 10% of the transcripts showed differential expression
      between the WT and Nrl(-/-) retina, with a fold change >=1.5 and p value <0.05.
      Altered expression of 25 genes was confirmed with qRT-PCR, demonstrating the high
      degree of sensitivity of the RNA-seq method. Hierarchical clustering of
      differentially expressed genes uncovered several as yet uncharacterized genes
      that may contribute to retinal function. Data analysis with BWA and TopHat
      workflows revealed a significant overlap yet provided complementary insights in
      transcriptome profiling. CONCLUSIONS: Our study represents the first detailed
      analysis of retinal transcriptomes, with biologic replicates, generated by RNA
      seq technology. The optimized data analysis workflows reported here should
      provide a framework for comparative investigations of expression profiles. Our
      results show that NGS offers a comprehensive and more accurate quantitative and
      qualitative evaluation of mRNA content within a cell or tissue. We conclude that
      RNA-seq based transcriptome characterization would expedite genetic network
      analyses and permit the dissection of complex biologic functions.

PMID- 22162624
TI  - Presence and distribution of the lubricating protein, lubricin, in the meibomian
      gland in rabbits.
AB  - PURPOSE: Lubricin is a principal boundary lubricating and anti-adhesion protein
      found in synovial fluid and several musculoskeletal tissues. This study
      investigates the presence of lubricin in the meibomian gland, lacrimal gland and
      ocular surface of healthy rabbits; prompted by the hypothesis that lubricin acts
      as boundary lubricant and anti-adhesive protein in the eye. METHODS: Thirty six
      eyelids were resected from ten cadaveric New Zealand White rabbits and two
      eyeballs and two lacrimal glands from two of them. Thirty two samples from 8
      animals were processed for immunohistochemical localization of lubricin using a
      purified monoclonal antibody and quantification of the lubricin-containing
      meibocytes. Confirmatory western blot analysis was performed on four eyelids from
      2 animals. RESULTS: Lubricin-positive meibomian cells were seen in the glands in
      all eight animals evaluated immunohistochemically. The percentage of lubricin
      positive cells ranged from was 8%-50% in the upper and 3%-50% in the lower
      eyelid, with no significant difference between the upper and lower eyelid.
      Western blot analysis confirmed the presence of lubricin ranging from 10 to 40 ng
      in four eyelids from the other two rabbits. Occasional staining was seen in the
      epithelium of the hair follicles of the eyelid. No lubricin was evident on the
      ocular surface or in the lacrimal gland. CONCLUSIONS: Lubricin is secreted by the
      meibomian gland. The results provide a basis for the hypothesis that lubricin
      plays a role in boundary lubrication and in preventing adhesions in the eye, as
      well as in contributing to other functions of the meibomian gland. Moreover, if
      lubricin functions to decrease the friction between the eyelid and ocular
      surface, this study provides a rationale to supplement the amount of lubricin in
      cases of compromised meibomian gland function and other conditions.

PMID- 22162625
TI  - Functional analysis of the Hsf4(lop11) allele responsible for cataracts in lop11
      mice.
AB  - PURPOSE: Lens opacity 11 (lop11) is a spontaneous autosomal recessive mouse
      mutation resulting in cataracts. Insertion of an early transposable element (ETn)
      in intron 9 of heat shock factor 4 (Hsf4) was previously identified as
      responsible for lop11 cataracts. Although molecular analysis showed that the ETn
      insertion resulted in an aberrant Hsf4 transcript encoding a truncated mutant
      HSF4(lop11) protein, the function of the mutant HSF4(lop11) protein was not
      investigated. The goal of this study was to functionally evaluate the mutant
      HSF4(lop11) protein and to establish the onset and progression of cataracts in
      lop11 lenses. METHODS: HSF4 is expressed as two alternatively transcribed
      isoforms Hsf4a and Hsf4b. Given that only Hsf4b is expressed in the lens we
      pursued evaluation of the mutant Hsf4b isoform only. Recombinant wild type HSF4b
      and mutant HSF4b(lop11) proteins were analyzed using elecrophoretic mobility
      shift, reporter transactivation, western blotting and protein half-life assays in
      HEK293 cells. Prenatal and postnatal wild type and lop11 lenses were evaluated
      using a combination of clinical, histological, and immunohistological analyses.
      RESULTS: HSF4b(lop11) stability and nuclear translocation of did not differ from
      wild type HSF4b. However, HSF4b(lop11) exhibited abolished HSE-mediated DNA
      binding and transactivation. Further investigation identified that HSF4b(lop11)
      fails to form trimers. Histological analysis of lop11 lenses indicated the
      persistence of nuclei in lens fiber cells as early as postnatal day 0.5 (P0.5).
      No differences were observed between wild type and lop11 in lens epithelial cell
      proliferation and spatio-temporal differentiation to fiber cells. However, by P10
      12, lop11 lenses develop severely vacuolated cataracts commonly accompanied by
      rupture of the lens capsule and release of the lenticular material in the
      vitreous cavity. Clinically, lop11 vacuolated cataracts were visible upon eyelid
      opening between P12-14. CONCLUSIONS: The ETn insertion in lop11 mice results in
      abolished HSF4b function. Loss of 132 amino acids from the COOH-terminus in
      HSF4b(lop11) results in the failure of trimer formation and subsequent failure of
      HSE-mediated DNA binding and transactivation. These findings highlight the
      importance of the COOH-terminal region for normal function. The persistence of
      nuclei in postnatal lop11 lens fiber cells was identified as the initial lens
      abnormality, thus confirming a previously identified role of HSF4b in
      denucleation of lens fiber cells. By P14 lop11 lenses develop severe fiber cell
      vacuoles although how the loss of HSF4b function results in this process remains
      unknown. Collectively, these findings further our understanding of the mechanism
      of HSF4 loss of function as well as the resulting implications on lop11
      cataractogenesis.

PMID- 22162626
TI  - IL-17A stimulates the production of inflammatory mediators via Erk1/2, p38 MAPK,
      PI3K/Akt, and NF-kappaB pathways in ARPE-19 cells.
AB  - PURPOSE: To investigate the signaling pathways involved in interleukin (IL)-17A 
      mediated production of interleukin 8 (CXCL8), chemokine (C-C motif) ligand 2
      (CCL2), and interleukin 6 (IL-6) by ARPE-19 cells, a spontaneously arisen cell
      line of retinal pigment epithelium (RPE). METHODS: Flow cytometry analysis and
      western blot were used to detect the phosphorylation of extracellular signal
      regulated kinases 1/2 (Erk1/2), p38 mitogen activated protein kinase (MAPK) and
      protein kinase B (PKB; Akt) in ARPE-19 cells stimulated with IL-17A. These cells
      were further pretreated with a series of kinase inhibitors and followed by
      incubation with IL-17A. CXCL8, CCL2, and IL-6 in the supernatant were quantified
      by enzyme-linked immunosorbent assay (ELISA). RESULTS: Coculture of ARPE-19 cells
      with IL-17A resulted in significant increases in Erk1/2, p38 MAPK, and Akt
      phosphorylation. Inhibition of p38MAPK, phosphoinositide 3-kinase (PI3K)-Akt and
      nuclear factor-kappaB (NF-kappaB), with the inhibitors SB203580, LY294002 and
      pyrrolydine dithiocarbamate (PDTC) respectively, reduced IL-17 (100 ng/ml)
      mediated production of CXCL8, CCL2, and IL-6 in a concentration dependent manner.
      Inhibition of Erk1/2 with PD98059 decreased the expression of the tested three
      inflammatory mediators when using low doses of IL-17A (0-10 ng/ml) but not at
      higher concentrations. CONCLUSIONS: IL-17A-induced production of inflammatory
      mediators by ARPE-19 cells involves Erk1/2, p38MAPK, PI3K-Akt and NF-kappaB
      pathways.

PMID- 22162627
TI  - Ocular phenotypes associated with biallelic mutations in BEST1 in Italian
      patients.
AB  - PURPOSE: To report on the phenotype and the genotype of Italian patients carrying
      BEST1 mutations on both alleles. METHODS: Five Italian patients from four
      independent pedigrees with retinal dystrophy associated with biallelic BEST1
      variants were recruited from different parts of Italy. Molecular genetic analysis
      of the BEST1 gene was performed with direct sequencing techniques. All the
      subjects included in the study were clinically evaluated with a standard
      ophthalmologic examination, fundus photography, optical coherence tomography
      scan, and electrophysiological investigations. RESULTS: Six BEST1 variants were
      identified. Three, c.1699del (p.Glu557AsnfsX52), c.625delAAC (p.Asn179del), and
      c.139C>T (p.Arg47Cys), were novel, and three had already been reported in the
      literature, c.301C>A(p.Pro101Thr), c.934G>A (p.Asp312Asn), and c.638A>G
      (p.Glu213Gly). Four were missense mutations, and two were deletions. Only one
      BEST1 mutation was located within one of the four mutational clusters described
      in typical autosomal dominant Best vitelliform macular dystrophy (BVMD). Four
      patients showed a BVMD phenotype while one patient presented a clinical picture
      consistent with autosomal recessive bestrophinopathy (ARB). CONCLUSIONS:
      Biallelic BEST1 sequence variants can be associated with at least two different
      phenotypes: BVMD and ARB. The phenotypic result of the molecular changes probably
      depends on the characteristics and the combination of the different BEST1
      mutations, but unknown modifying factors such as other genes or the environment
      may also play a role.

PMID- 22162628
TI  - Polymorphisms in the vascular endothelial growth factor gene and the risk of
      diabetic retinopathy in Chinese patients with type 2 diabetes.
AB  - PURPOSE: To investigate whether single nucleotide polymorphisms (SNPs) in the
      vascular endothelial growth factor (VEGF) gene are associated with diabetic
      retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus
      (T2DM). METHODS: A total of 268 patients with T2DM (129 with DR and 139 without
      DR) were recruited and enrolled in the study. Patients with T2DM were assigned to
      a DR group or a diabetic-without-retinopathy group, based on the duration of
      diabetes and grading of fundus images. Genotypes of eight SNPs in the VEGF gene
      (rs699947, rs833061, rs13207351, rs2010963, rs833069, rs2146323, rs3025021, and
      rs3025039) were analyzed using a mass-array genotyping system, and an association
      study was performed. RESULTS: After adjusting for covariates, a significant
      association of DR was observed with the homozygous genotype of the minor allele
      for promoter SNPs rs699947 (odds ratio (OR)=3.54, 95% confidence interval (CI):
      1.12-11.19), rs833061 (OR=3.72, 95% CI: 1.17-11.85) and rs13207351 (OR=3.76, 95%
      CI: 1.21-11.71). A significant association of DR was also observed with haplotype
      ACA, as defined by minor alleles of promoter SNPs rs699947, rs833061, and
      rs13207351 (OR=1.52, 95% CI: 1.03-2.24), and haplotype GAA, as defined by SNPs
      rs2010963, rs833069, and rs2146323 (OR=1.62, 95% CI: 1.08-2.41). CONCLUSIONS: Our
      data suggest that polymorphisms in the promoter region of the VEGF gene increase
      the risk of DR in Chinese patients with T2DM.

PMID- 22162629
TI  - Toward personalized cell therapies: autologous menstrual blood cells for stroke.
AB  - Cell therapy has been established as an important field of research with
      considerable progress in the last years. At the same time, the progressive aging
      of the population has highlighted the importance of discovering therapeutic
      alternatives for diseases of high incidence and disability, such as stroke.
      Menstrual blood is a recently discovered source of stem cells with potential
      relevance for the treatment of stroke. Migration to the infarct site, modulation
      of the inflammatory reaction, secretion of neurotrophic factors, and possible
      differentiation warrant these cells as therapeutic tools. We here propose the use
      of autologous menstrual blood cells in the restorative treatment of the subacute
      phase of stroke. We highlight the availability, proliferative capacity,
      pluripotency, and angiogenic features of these cells and explore their
      mechanistic pathways of repair. Practical aspects of clinical application of
      menstrual blood cells for stroke will be discussed, from cell harvesting and
      cryopreservation to administration to the patient.

PMID- 22162630
TI  - Explanting is an ex vivo model of renal epithelial-mesenchymal transition.
AB  - Recognised by their de novo expression of alpha-smooth muscle actin (SMA),
      recruitment of myofibroblasts is key to the pathogenesis of fibrosis in chronic
      kidney disease. Increasingly, we realise that epithelial-mesenchymal transition
      (EMT) may be an important source of these cells. In this study we describe a
      novel model of renal EMT. Rat kidney explants were finely diced on gelatin-coated
      Petri dishes and cultured in serum-supplemented media. Morphology and
      immunocytochemistry were used to identify mesenchymal (vimentin+, alpha-smooth
      muscle actin (SMA)+, desmin+), epithelial (cytokeratin+), and endothelial (RECA+)
      cells at various time points. Cell outgrowths were all epithelial in origin
      (cytokeratin+) at day 3. By day 10, 50 +/- 12% (mean +/- SE) of cytokeratin+
      cells double-labelled for SMA, indicating EMT. Lectin staining established a
      proximal tubule origin. By day 17, cultures consisted only of myofibroblasts
      (SMA+/cytokeratin-). Explanting is a reproducible ex vivo model of EMT. The
      ability to modify this change in phenotype provides a useful tool to study the
      regulation and mechanisms of renal tubulointerstitial fibrosis.

PMID- 22162632
TI  - Possible involvement of tight junctions, extracellular matrix and nuclear
      receptors in epithelial differentiation.
AB  - Tight junctions are intercellular junctions localized at the most apical end of
      the lateral plasma membrane. They consist of four kinds of transmembrane proteins
      (occludin, claudins, junctional adhesion molecules, and tricellulin) and huge
      numbers of scaffolding proteins and contribute to the paracellular barrier and
      fence function. The mutation and deletion of these proteins impair the functions
      of tight junctions and cause various human diseases. In this paper, we provide an
      overview of recent studies on transmembrane proteins of tight junctions and
      highlight the functional significance of tight junctions, extracellular matrix,
      and nuclear receptors in epithelial differentiation.

PMID- 22162634
TI  - Titin-actin interaction: PEVK-actin-based viscosity in a large animal.
AB  - Titin exhibits an interaction between its PEVK segment and the actin filament
      resulting in viscosity, a speed dependent resistive force, which significantly
      influences diastolic filling in mice. While diastolic disease is clinically
      pervasive, humans express a more compliant titin (N2BA:N2B ratio ~0.5-1.0) than
      mice (N2BA:N2B ratio ~0.2). To examine PEVK-actin based viscosity in compliant
      titin-tissues, we used pig cardiac tissue that expresses titin isoforms similar
      to that in humans. Stretch-hold experiments were performed at speeds from 0.1 to
      10 lengths/s from slack sarcomere lengths (SL) to SL of 2.15 MUm. Viscosity was
      calculated from the slope of stress-relaxation vs stretch speed. Recombinant PEVK
      was added to compete off native interactions and this found to reduce the slope
      by 35%, suggesting that PEVK-actin interactions are a strong contributor of
      viscosity. Frequency sweeps were performed at frequencies of 0.1-400 Hz and
      recombinant protein reduced viscous moduli by 40% at 2.15 MUm and by 50% at 2.25
      MUm, suggesting a SL-dependent nature of viscosity that might prevent SL
      "overshoot" at long diastolic SLs. This study is the first to show that viscosity
      is present at physiologic speeds in the pig and supports the physiologic
      relevance of PEVK-actin interactions in humans in both health and disease.

PMID- 22162633
TI  - Activation of type I interferon pathway in systemic lupus erythematosus:
      association with distinct clinical phenotypes.
AB  - Growing evidence over the last few years suggests a central role of type I IFN
      pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical
      and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus
      prone mouse models, indicates that the type I interferon system may play a
      pivotal role in the pathogenesis of several lupus and associated clinical
      features, such as nephritis, neuropsychiatric and cutaneous lupus, premature
      atherosclerosis as well as lupus-specific autoantibodies particularly against
      ribonucleoproteins. In the current paper, our aim is to summarize the latest
      findings supporting the association of type I IFN pathway with specific clinical
      manifestations in the setting of SLE providing insights on the potential use of
      type I IFN as a therapeutic target.

PMID- 22162636
TI  - Phasic and tonic smooth muscle function of the partially obstructed guinea pig
      intestine.
AB  - This study was to generate phasic and tonic stress-strain curves for evaluation
      of smooth muscle function in the obstructed guinea pig jejunum. Partial and sham
      obstruction of the jejunum in guinea pigs was created surgically, with guinea
      pigs not being operated on served as normal controls. The animals survived 2, 4,
      7, and 14 days, respectively. The jejunal segment was distended to 10 cm H(2)O.
      The pressure and outer diameter changes were recorded. Passive conditions were
      obtained by using papaverine. Total phasic, tonic, and passive circumferential
      stress and strain were computed from the diameter and pressure data with
      reference to the zero-stress-state geometry. The active phasic and tonic stresses
      were defined as the total phasic and tonic stress minus the passive stress. The
      thickness of intestinal muscle layers increased in a time-dependent manner after
      obstruction. The amplitude of passive, total phasic, total tonic, active phasic,
      and active tonic circumferential stresses increased as function of strain 7 days
      after obstruction. However, when normalized to muscle layer thickness, the
      amplitude of active stresses did not differ among the groups. In conclusion, the
      long-term-obstructed intestine exhibits increased total smooth muscle contraction
      force. However, the contraction force per smooth muscle unit did not increase.

PMID- 22162635
TI  - Modeling neurological disorders by human induced pluripotent stem cells.
AB  - Studies of human brain development are critical as research on neurological
      disorders have been progressively advanced. However, understanding the process of
      neurogenesis through analysis of the early embryo is complicated and limited by a
      number of factors, including the complexity of the embryos, availability, and
      ethical constrains. The emerging of human embryonic stem cells (hESCs) and
      induced pluripotent stem cells (iPSCs) has shed light of a new approach to study
      both early development and disease pathology. The cells behave as precursors of
      all embryonic lineages; thus, they allow tracing the history from the root to
      individual branches of the cell lineage tree. Systems for neural differentiation
      of hESCs and iPSCs have provided an experimental model that can be used to
      augment in vitro studies of in vivo brain development. Interestingly, iPSCs
      derived from patients, containing donor genetic background, have offered a
      breakthrough approach to study human genetics of neurodegenerative diseases. This
      paper summarizes the recent reports of the development of iPSCs from patients who
      suffer from neurological diseases and evaluates the feasibility of iPSCs as a
      disease model. The benefits and obstacles of iPSC technology are highlighted in
      order to raising the cautions of misinterpretation prior to further clinical
      translations.

PMID- 22162637
TI  - The IQ motif is crucial for Cav1.1 function.
AB  - Ca(2+)-dependent modulation via calmodulin, with consensus CaM-binding IQ motif
      playing a key role, has been documented for most high-voltage-activated Ca(2+)
      channels. The skeletal muscle Ca(v)1.1 also exhibits Ca(2+)-/CaM-dependent
      modulation. Here, whole-cell Ca(2+) current, Ca(2+) transient, and maximal,
      immobilization-resistant charge movement (Q(max)) recordings were obtained from
      cultured mouse myotubes, to test a role of IQ motif in function of Ca(v)1.1. The
      effect of introducing mutation (IQ to AA) of IQ motif into Ca(v)1.1 was examined.
      In dysgenic myotubes expressing YFP-Ca(v)1.1(AA), neither Ca(2+) currents nor
      evoked Ca(2+) transients were detectable. The loss of Ca(2+) current and
      excitation-contraction coupling did not appear to be a consequence of defective
      trafficking to the sarcolemma. The Q(max) in dysgenic myotubes expressing YFP
      Ca(v)1.1(AA) was similar to that of normal myotubes. These findings suggest that
      the IQ motif of the Ca(v)1.1 may be an unrecognized site of structural and
      functional coupling between DHPR and RyR.

PMID- 22162638
TI  - Sex steroids effects on the molting process of the helminth human parasite
      Trichinella spiralis.
AB  - We evaluated the in vitro effects of estradiol, progesterone, and testosterone on
      the molting process, which is the initial and crucial step in the development of
      the muscular larvae (ML or L1) to adult worm. Testosterone had no significative
      effect on the molting rate of the parasite, however, progesterone decreased the
      molting rate about a 50% in a concentration- and time-independent pattern, while
      estradiol had a slight effect (10%). The gene expression of caveolin-1, a
      specific gene used as a marker of parasite development, showed that progesterone
      and estradiol downregulated its expression, while protein expression was
      unaffected. By using flow citometry, a possible protein that is recognized by a
      commercial antiprogesterone receptor antibody was detected. These findings may
      have strong implications in the host-parasite coevolution, in the sex-associated
      susceptibility to this infection and could point out to possibilities to use
      antihormones to inhibit parasite development.

PMID- 22162639
TI  - Bioequivalence of oxymorphone extended release and crush-resistant oxymorphone
      extended release.
AB  - BACKGROUND: A formulation of crush-resistant extended-release opioids may deter
      abuse. The purpose of this study was to evaluate the bioequivalence of
      oxymorphone extended-release (Oxy-ER) and a crush-resistant formulation of
      oxymorphone extended-release (Oxy-CRF). METHODS: In three open-label, randomized
      studies, healthy adults at a clinical research center received two single oral
      doses of Oxy-ER and two single doses of Oxy-CRF, each separated by a >=7-day
      washout. Doses were administered under fasted conditions (study 1, 5 mg doses;
      study 2, 40 mg doses) or after a high-fat breakfast (study 3, 40 mg doses).
      Subjects administered 40 mg doses also received naltrexone. The primary endpoint
      was systemic oxymorphone exposure; the bioequivalence criterion was met if the
      90% confidence intervals of the geometric mean ratio (Oxy-CRF/Oxy-ER) for
      oxymorphone area under the curve from time 0 to the last measured concentration
      (AUC(0-t)), AUC from time 0 to infinity (AUC(0-inf)), and maximum plasma
      concentration (C(max)) were within 0.8-1.25. Safety was assessed by monitoring
      adverse events. RESULTS: In studies 1, 2, and 3, the safety population comprised
      30, 37, and 36 subjects and the pharmacokinetics population comprised 27, 30, and
      29 subjects, respectively. Oxy-ER and Oxy-CRF produced similar mean +/- standard
      deviation oxymorphone AUC(0-t) (study 1, 5.05 +/- 1.55 versus 5.29 +/- 1.52 ng .
      h/mL; study 2, 31.51 +/- 10.95 versus 31.23 +/- 10.33 ng . h/mL; study 3, 50.16
      +/- 14.91 versus 49.01 +/- 14.03 ng . h/mL) and C(max) (0.38 +/- 0.11 versus 0.37
      +/- 0.12 ng/mL; 2.37 +/- 1.20 versus 2.41 +/- 0.94 ng/mL; 5.87 +/- 1.99 versus
      5.63 +/- 2.26 ng/mL) under all conditions. The 90% confidence intervals for
      plasma oxymorphone AUC(0-t), AUC(0-inf), and C(max) fulfilled the bioequivalence
      criterion. Adverse event rates were similar with Oxy-ER and Oxy-CRF (study 1, 25%
      versus 23%; study 2, 9% versus 16%; study 3, 20% each group). CONCLUSION: Oxy-CRF
      and Oxy-ER (5 mg and 40 mg) are bioequivalent under fasted and fed conditions,
      suggesting that Oxy-CRF will have clinical efficacy and safety equivalent to Oxy
      ER.

PMID- 22162640
TI  - The influence of operational parameters and feed preparation in a convective
      batch ribbon powder mixer.
AB  - PURPOSE: To investigate the effect of feed preparation characteristics and
      operational parameters on mixing homogeneity in a convective batch ribbon mixer.
      METHODS: Lactose 100M, lactose 200M, ascorbic acid, and zinc oxide powders were
      used for the mixing study. Operational parameters studied were rotational speed
      and mixing time. The feed preparations studied were the use of preblending and
      the particle size of the feed materials. The blends of ascorbic acid, zinc oxide,
      and lactose were prepared with preblending and without preblending, prior to
      mixing at different blender rotation speeds and mixing times. Chemical tests were
      performed to measure the homogeneity of the ascorbic acid in the model mixture.
      RESULTS: With preblending, a mixture with lactose 200M achieved the required
      homogeneity in a shorter period of time at a lower rotational speed. CONCLUSION:
      The results indicated that the homogeneity of the mixtures was influenced by the
      blender rotation speed and mixing time. Better mixing can be obtained with higher
      rotation speeds and longer mixing time. It was also observed that preblending and
      smaller feed particle size achieved the required homogeneity in a shorter period
      of time at a lower rotational speed. These results illustrate that using binders
      with a smaller particle size and a preblending technique improves the mixing
      process in a convective batch ribbon powder mixer. However, prolonged periods of
      high-speed mixing will lead to mixture segregation.

PMID- 22162641
TI  - Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor
      for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung
      cancer and beyond.
AB  - Epidermal growth factor receptor (EGFR) tyrosine inhibitors were first approved
      for the treatment of non-small cell lung cancer (NSCLC) in 2003 in the US.
      Activating EGFR mutations were subsequently discovered in 2004, and heralded the
      era of molecular targeted therapy in NSCLC. The discovery of anaplastic lymphoma
      kinase (ALK) rearrangement in NSCLC in 2007 by two independent groups not only
      represents the first time ALK rearrangement has been discovered in common solid
      tumors but also represents another important milestone in the era of molecular
      targeted therapy in NSCLC. Crizotinib, a mesenchymal-epithelial transition
      (MET)/ALK multi-targeted receptor tyrosine kinase inhibitor went into early Phase
      I clinical development in 2007. Using the knowledge that NSCLC patients with
      activating EGFR mutations benefited from EGFR tyrosine kinase inhibitors,
      crizotinib was rapidly and successfully developed as an inhibitor in ALK
      rearranged NSCLC, based on a break apart fluorescence in situ hybridization
      assay, developed by two of the crizotinib Phase I sites. It cumulated in the
      conditional approval of crizotinib by the US Food and Drug Administration on
      August 26, 2011 for the treatment of ALK-rearranged NSCLC. The conditional
      approval was based on response rates of 50% and 61% from 255 ALK-rearranged NSCLC
      patients enrolled in two single-arm trials. Common adverse events of crizotinib
      include mild transient visual disorders, mild gastrointestinal toxicities,
      fatigue, rare alanine transaminase elevations, and even rarer pneumonitis (1.6%).
      Confirmatory trials comparing crizotinib with standard chemotherapy are ongoing.
      It took an unprecedented four years from the discovery of ALK rearrangement in
      NSCLC to the approval of crizotinib, the first ever ALK inhibitor, for the
      treatment of ALK-rearranged NSCLC.

PMID- 22162643
TI  - Antibody-induced secondary treatment failure in a patient treated with botulinum
      toxin type A for glabellar frown lines.
AB  - Botulinum toxin type A (BTX-A) preparations are widely used nonsurgical
      treatments for facial wrinkles. Higher doses of BTX-A are also used for
      therapeutic purposes in the treatment of conditions involving increased muscle
      tone, such as cervical dystonia. The phenomenon of antibody-induced treatment
      failure is well known in the therapeutic setting, but reports are also emerging
      following cosmetic use of BTX-A. We describe the case of a 41-year-old female
      nurse who developed secondary treatment failure during 6 years of BTX-A treatment
      for glabellar lines. After a good response to the first BTX-A injection, the
      intensity and duration of effect decreased after subsequent treatments. Antibody
      tests revealed a high titer of neutralizing anti-BTX-A antibodies. This case
      shows secondary treatment failure due to the production of neutralizing
      antibodies following administration of BTX-A formulations for cosmetic purposes
      and demonstrates that immunogenicity of BTX-A preparations is an important
      consideration, even in the cosmetic setting.

PMID- 22162644
TI  - The variations of body mass index and body fat in adult Thai people across the
      age spectrum measured by bioelectrical impedance analysis.
AB  - BACKGROUND: The measurements of body mass index (BMI) and percentage of body fat
      are used in many clinical situations. However, special tools are required to
      measure body fat. Many formulas are proposed for estimation but these use
      constant coefficients of age. Age spectrum might affect the predicted value of
      the body composition due to body component alterations, and the coefficient of
      age for body fat prediction might produce inconsistent results. The objective of
      this study was to identify variations of BMI and body fat across the age spectrum
      as well as compare results between BMI predicted body fat and bioelectrical
      impedance results on age. METHODS: Healthy volunteers were recruited for this
      study. Body fat was measured by bioelectrical impedance. The age spectrum was
      divided into three groups (younger: 18-39.9; middle: 40-59.9; and older: >=60
      years). Comparison of body composition covariates including fat mass (FM), fat
      free mass (FFM), percentage FM (PFM), percentage FFM (PFFM), FM index (FMI) and
      FFM index (FFMI) in each weight status and age spectrum were analyzed.
      Multivariable linear regression coefficients were calculated. Coefficient
      alterations among age groups were tested to confirm the effect of the age
      spectrum on body composition covariates. Measured PFM and calculated PFM from
      previous formulas were compared in each quarter of the age spectrum. RESULTS: A
      total of 2324 volunteers were included in this study. The overall body
      composition and weight status, average body weight, height, BMI, FM, FFM, and its
      derivatives were significantly different among age groups. The coefficient of age
      altered the PFM differently between younger, middle, and older groups (0.07; P =
      0.02 vs 0.13; P < 0.01 vs 0.26; P < 0.01; respectively). All coefficients of age
      alterations in all FM- and FFM-derived variables between each age spectrum were
      tested, demonstrating a significant difference between the younger (<60 years)
      and older (>=60 years) age groups, except the PFFM to BMI ratio (difference of
      PFM and FMI [95% confidence interval]: 17.8 [12.8-22.8], P < 0.01; and 4.58 [3.4
      5.8], P < 0.01; respectively). The comparison between measured PFM and calculated
      PFM demonstrated a significant difference with increments of age. CONCLUSION: The
      relationship between body FM and BMI varies on the age spectrum. A calculated
      formula in older people might be distorted with the utilization of constant
      coefficients.

PMID- 22162645
TI  - Ethnic-based differences in the association of self-perceived health status and
      doctor's office utilization: Longitudinal Study on Aging.
AB  - BACKGROUND: The purpose of this study was to determine whether self-perceived
      health status is predictive of a doctor's office visit in the Longitudinal Study
      on Aging (LSOA). METHODS: This was a population-based longitudinal study of
      persons aged >=70 years who participated in the Study on Aging in 1984 and a
      follow-up survey of the LSOA in 1986. The cohort for the study consisted of 560
      blacks and 6880 whites who were 70 years or older in 1984. Multivariable logistic
      regression analysis was performed separately for blacks and for whites. RESULTS:
      The study sample was predominantly Caucasian (91.2%) with a mean age 76.8 +/- 5.5
      years and mean education grade 10 +/- 3.7. The majority (82%) lived above the
      poverty level. Self-reported poor health status predicted the use of doctor's
      office services among whites (odds ratio [OR] 5.15; 95% confidence interval [CI]
      3.34-7.95), but not in blacks (OR 1.6; 95% CI 0.54-4.76). CONCLUSION: Self
      perceived health status predicted the use of doctor's office services among older
      whites but not in older blacks in the LSOA.

PMID- 22162646
TI  - Successful long-term weight loss maintenance in a rural population.
AB  - BACKGROUND: Few investigations of successful long-term weight loss beyond two
      years have been conducted, and none has examined weight changes in medically
      underserved rural populations of older adults. The purpose of this study was to
      assess long-term weight loss maintenance 3.5 years after the completion of an
      initial six-month lifestyle intervention for obesity among women aged 50-75 years
      residing in rural communities. METHODS: One hundred and ten obese women with a
      mean (+/- standard deviation) age of 60.08 +/- 6.17 years and mean body mass
      index of 36.76 +/- 5.10 kg/m(2) completed an in-person assessment during which
      their weight and adherence to behavioral weight management strategies were
      evaluated. RESULTS: Participants showed a mean weight reduction of 10.17% +/-
      5.0% during the initial six- month intervention and regained 6.95% +/- 9.44% from
      the completion of treatment to follow-up assessment 3.5 years later. A
      substantial proportion of participants (41.80%) were able to maintain weight
      reductions of 5% or greater from baseline to follow-up. "Successful" participants
      (those who maintained losses of 5% or greater at follow-up) reported weighing
      themselves, self-monitoring their intake and calories, planning meals in advance,
      and choosing lower calorie foods with greater frequency than "unsuccessful"
      participants (those who lost less than 5%). CONCLUSION: Collectively, these
      findings indicate that a large proportion of participants were able to maintain
      clinically significant weight losses for multiple years after treatment, and that
      self-monitoring was a key component of successful long-term weight management.

PMID- 22162647
TI  - Implementing chronic care for COPD: planned visits, care coordination, and
      patient empowerment for improved outcomes.
AB  - Current primary care patterns for chronic obstructive pulmonary disease (COPD)
      focus on reactive care for acute exacerbations, often neglecting ongoing COPD
      management to the detriment of patient experience and outcomes. Proactive
      diagnosis and ongoing multifactorial COPD management, comprising smoking
      cessation, influenza and pneumonia vaccinations, pulmonary rehabilitation, and
      symptomatic and maintenance pharmacotherapy according to severity, can
      significantly improve a patient's health-related quality of life, reduce
      exacerbations and their consequences, and alleviate the functional, utilization,
      and financial burden of COPD. Redesign of primary care according to principles of
      the chronic care model, which is implemented in the patient-centered medical
      home, can shift COPD management from acute rescue to proactive maintenance. The
      chronic care model and patient-centered medical home combine delivery system
      redesign, clinical information systems, decision support, and self-management
      support within a practice, linked with health care organization and community
      resources beyond the practice. COPD care programs implementing two or more
      chronic care model components effectively reduce emergency room and inpatient
      utilization. This review guides primary care practices in improving COPD care
      workflows, highlighting the contributions of multidisciplinary collaborative team
      care, care coordination, and patient engagement. Each primary care practice can
      devise a COPD care workflow addressing risk awareness, spirometric diagnosis,
      guideline-based treatment and rehabilitation, and self-management support, to
      improve patient outcomes in COPD.

PMID- 22162648
TI  - Cognitive behavioral therapy for insomnia comorbid with COPD is feasible with
      preliminary evidence of positive sleep and fatigue effects.
AB  - BACKGROUND: Many people with COPD report difficulties falling asleep or staying
      asleep, insufficient sleep duration, or nonrestorative sleep. Cognitive
      behavioral therapy for insomnia (CBT-I) has proved effective not only in people
      with primary insomnia but also in people with insomnia comorbid with psychiatric
      and medical illness (eg, depression, cancer, and chronic pain). However, CBT-I
      has rarely been tested in those with COPD who have disease-related features that
      interfere with sleep and may lessen the effectiveness of such therapies. The
      purpose of this study was to determine the feasibility of applying a CBT-I
      intervention for people with COPD and to assess the impact of CBT-I on insomnia
      severity and sleep-related outcomes, fatigue, mood, and daytime functioning.
      METHODS: The study had two phases. In Phase 1, a 6-weekly session CBT-I
      intervention protocol in participants with COPD was assessed to examine
      feasibility and acceptability. Phase 2 was a small trial utilizing a prospective
      two-group pre- and post-test design with random assignment to the six-session CBT
      I or a six-session wellness education (WE) program to determine the effects of
      each intervention, with both interventions being provided by a nurse behavioral
      sleep medicine specialist. RESULTS: Fourteen participants (five in Phase 1 and
      nine in Phase 2) completed six sessions of CBT-I and nine participants completed
      six sessions of WE. Participants indicated that both interventions were
      acceptable. Significant positive treatment-related effects of the CBT-I
      intervention were noted for insomnia severity (P = 0.000), global sleep quality
      (P = 0.002), wake after sleep onset (P = 0.03), sleep efficiency (P = 0.02),
      fatigue (P = 0.005), and beliefs and attitudes about sleep (P = 0.000).
      Significant positive effects were noted for depressed mood after WE (P = 0.005).
      CONCLUSION: Results suggest that using CBT-I in COPD is feasible and the outcomes
      compare favorably with those obtained in older adults with insomnia in the
      context of other chronic illnesses.

PMID- 22162649
TI  - Functional imaging using computer methods to compare the effect of salbutamol and
      ipratropium bromide in patient-specific airway models of COPD.
AB  - BACKGROUND: Salbutamol and ipratropium bromide improve lung function in patients
      with chronic obstructive pulmonary disease (COPD). However, their bronchodilating
      effect has not yet been compared in the central and distal airways. Functional
      imaging using computational fluid dynamics offers the possibility of making such
      a comparison. The objective of this study was to assess the effects of salbutamol
      and ipratropium bromide on the geometry and computational fluid dynamics-based
      resistance of the central and distal airways. METHODS: Five patients with Global
      Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to
      a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1
      week interval between treatments. Patients underwent lung function testing and a
      multislice computed tomography scan of the thorax that was used for functional
      imaging. Two hours after dosing, the patients again underwent lung function tests
      and repeat computed tomography. RESULTS: Lung function parameters, including
      forced expiratory volume in 1 second, vital capacity, overall airway resistance,
      and specific airway resistance, changed significantly after administration of
      each product. On functional imaging, the bronchodilating effect was greater in
      the distal airways, with a corresponding drop in airway resistance, compared with
      the central airways. Salbutamol and ipratropium bromide were equally effective at
      first glance when looking at lung function tests, but when viewed in more detail
      with functional imaging, hyporesponsiveness could be shown for salbutamol in one
      patient. Salbutamol was more effective in the other patients. CONCLUSION: This
      pilot study gives an innovative insight into the modes of action of salbutamol
      and ipratropium bromide in patients with COPD, using the new techniques of
      functional imaging and computational fluid dynamics.

PMID- 22162650
TI  - Outcome of pulmonary rehabilitation in COPD patients with severely impaired
      health status.
AB  - INTRODUCTION: Effects of pulmonary rehabilitation (PR) in chronic obstructive
      pulmonary disease (COPD) patients with severely impaired health status are poorly
      documented since these patients are usually excluded from clinical trials. This
      retrospective, observational study aims to study the impact of disease on health
      status and the effects of PR on COPD patients referred to a tertiary center for
      PR in The Netherlands. METHODS: Between June 2006 and June 2010, 437 patients
      with COPD were allocated to our intensive, comprehensive PR program. Patients
      participated in this interdisciplinary program for 12 weeks for a weekly average
      of 20-25 hours. Before and directly after, several measures of physical
      performance and health-related quality of life were determined. RESULTS: At
      baseline, most patients (75%) had a Global Initiative for Chronic Obstructive
      Lung Disease (GOLD) stage of III-IV. Peak exercise performance on a cycle
      ergometer was on average reduced to 43 +/- 29 Watt, and health-related quality of
      life was significantly impaired, with a total score on the St George's
      Respiratory Questionnaire (SGRQ) of 66. Health-care utilization in the year
      preceding PR was very high. After rehabilitation, all outcome measures improved
      statistically significantly (P < 0.001). Exercise performance measured with the 6
      minute walking distance test improved clinically significantly in 68% of the
      patients, whereas 75% of the patients showed a clinically meaningful improvement
      in quality of life as measured with the SGRQ. Multiple regression analysis
      revealed that 19% of the variation in responses on the 6 minute walking distance
      test and the SGRQ could be explained on the basis of baseline characteristics.
      CONCLUSION: The present study provides data to indicate that COPD patients may
      substantially benefit from rehabilitation in a tertiary pulmonary rehabilitation
      center, despite a severely impaired health status and high level of health-care
      utilization, in which prior treatment in primary and secondary care have failed
      to improve health status. Individual rehabilitation responses can only partially
      be predicted on the basis of baseline characteristics. Consequently, no firm
      conclusions can be drawn from this study with respect to the selection of
      candidates that could be deemed eligible for this rehabilitation program when
      entering the program.

PMID- 22162651
TI  - Biosynthesis of gold nanoparticles using chloroplasts.
AB  - In this paper, a new method of one-pot biosynthesizing of gold nanoparticles
      (GNPs), using chloroplasts as reductants and stabilizers is reported. The as
      prepared GNPs were characterized by ultraviolet visible spectroscopy,
      transmission electron microscopy, X-ray powder diffraction, and Fourier transform
      infrared spectroscopy (FTIR). The cytotoxicity of the GNPs was evaluated using
      the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method
      against gastric mucous cell line GES-1 and gastric cancer cell line MGC-803.
      Rhodamine 6G as a Raman probe was used for investigating surface-enhanced Raman
      spectroscopy (SERS) enhancement of GNPs. The transmission electron microscopy
      results indicated that the GNPs were spherical in structure and almost 20 nm in
      diameter. Ultraviolet visible spectroscopy exhibited an absorption peak at 545
      nm. The GNPs exhibited high crystallinity, with the (111) plane as the
      predominant orientation, clarified by X-ray powder diffraction. In addition, a
      potential mechanism was proposed to interpret the formation process of GNPs,
      mainly based on the analysis of FTIR results. The FTIR spectrum confirmed that
      the GNPs were carried with N-H groups. Toxicological assays of as-prepared GNPs
      revealed that the green GNPs were nontoxic. SERS analysis revealed that the GNPs
      without any treatment could substantially enhance the Raman signals of rhodamine
      6G. The Raman enhancement factor was calculated to be nearly 10(10) orders of
      magnitude. In conclusion, the GNPs with good biocompatibility and excellent SERS
      effect were successfully synthesized using chloroplasts. These biogenetic GNPs
      have great potential for ultrasensitive detection of biomarkers in vitro and in
      vivo based on SERS.

PMID- 22162652
TI  - Coupling technique of random amplified polymorphic DNA and nanoelectrochemical
      sensor for mapping pancreatic cancer genetic fingerprint.
AB  - OBJECTIVE: To review the feasibility of coupling the techniques of random
      amplified polymorphic DNA (RAPD) with carbon nanotube-based modified electrode
      for guanine/deoxyguanine triphosphate (dGTP) electrochemical sensing for mapping
      of the pancreatic cancer genetic fingerprint and screening of genetic
      alterations. METHODS: We developed a new method to study the electrochemical
      behavior of dGTP utilizing carbon multiwalled nanotube (MWNT)-modified glassy
      carbon electrodes (GCEs). RAPD was applied for amplification of DNA samples from
      healthy controls and patients with pancreatic cancer under the same conditions to
      determine the different surplus quantity of dGTP in the polymerase chain reaction
      (PCR), thereby determining the difference/quantity of PCR products or template
      strands. Using this method we generated a genetic fingerprint map of pancreatic
      cancer through the combination of electrochemical sensors and gel electrophoresis
      to screen for genetic alterations. Cloning and sequencing were then performed to
      verify these gene alterations. RESULTS: dGTP showed favorable electrochemical
      behavior on the MWNTs/GCE. The results indicated that the electrical signal and
      dGTP had a satisfactory linear relationship with the dGTP concentration within
      the conventional PCR concentration range. The MWNTs/GCE could distinguish between
      different products of RAPD. This experiment successfully identified a new
      pancreatic cancer-associated mutant gene fragment, consisting of a cyclin
      dependent kinase 4 gene 3' terminal mutation. CONCLUSION: The coupling of RAPD
      and nanoelectrochemical sensors was successfully applied to the screening of
      genetic alterations in pancreatic cancer and for mapping of DNA fingerprints.

PMID- 22162653
TI  - Oral fondaparinux: use of lipid nanocapsules as nanocarriers and in vivo
      pharmacokinetic study.
AB  - Oral anticoagulant therapy could be advanced using lipid-based nanoparticulate
      systems. This study examined lipid nanocapsules for their oral absorption
      potential as the first step in developing oral fondaparinux (Fp) novel carriers.
      Using phase inversion method and cationic surfactants such as hexadecyltrimethyl
      ammonium bromide (CTAB) or stearylamine (SA), cationic lipid nanocapsules
      (cLNCs), loaded with Fp on their surface, were prepared and characterized (zeta
      potential, size and Fp association efficiency and content). In vivo studies were
      conducted after single oral increasing doses of Fp-loaded cLNCs (0.5 to 5 mg/kg
      of Fp) in rats and the concentration of Fp in the plasma was measured by anti
      factor Xa activity assay. The monodisperse, (~50 nm), positively charged Fp-cLNCs
      with high drug loadings demonstrated linear pharmacokinetic profiles of the drug
      with an increased oral absolute bioavailability (up to ~21%) compatible with
      therapeutic anticoagulant effect (>0.2 MUg/mL).

PMID- 22162654
TI  - Lipid nanoparticles as delivery vehicles for the Parietaria judaica major
      allergen Par j 2.
AB  - Parietaria pollen is one of the major causes of allergic reaction in southern
      Europe, affecting about 30% of all allergic patients in this area. Specific
      immunotherapy is the only treatment able to modify the natural outcome of the
      disease by restoring a normal immunity against allergens. The preparation of
      allergen-solid lipid nanoparticles as delivery vehicles for therapeutic proteins,
      P. judaica major allergen Par j 2, was investigated. The Par j 2 allergen was
      expressed in a large amount in Escherichia coli and purified to homogeneity. Its
      immunological properties were studied by western blotting and enzyme-linked
      immunosorbent assay inhibition. Solid lipid nanoparticles were obtained by water
      in-oil-in-water multiple emulsion method and characterized in terms of mean size
      and surface charge. These systems (approximately 250 nm diameter and negative
      surface charge) incorporated recombinant Par j 2 with 40% or greater efficiency.
      Moreover, the endotoxin level and anaphylactic activity of the empty solid lipid
      nanoparticles and recombinant Par j 2-loaded solid lipid nanoparticles were
      evaluated by looking at the overexpression of CD203c marker on human basophils.
      These results demonstrate that recombinant Par j 2-nanoparticles could be
      proposed as safe compositions for the development of new therapeutic dosage forms
      to cure allergic reactions.

PMID- 22162656
TI  - Synthesis of biocompatible poly(E-caprolactone)- block-poly(propylene adipate)
      copolymers appropriate for drug nanoencapsulation in the form of core-shell
      nanoparticles.
AB  - Poly(propylene adipate)-block-poly(E-caprolactone) copolymers were synthesized
      using a combination of polycondensation and ring-opening polymerization of E
      caprolactone in the presence of poly(propylene adipate). Gel permeation
      chromatography was used for molecular weight determination, whereas hydrogen-1
      nuclear magnetic resonance and carbon-13 nuclear magnetic resonance spectroscopy
      were employed for copolymer characterization and composition evaluation. The
      copolymers were found to be block while their composition was similar to the
      feeding ratio. They formed semicrystalline structures, while only poly(E
      caprolactone) formed crystals, as shown by wide angle X-ray diffraction.
      Differential scanning calorimetry data suggest that the melting point and heat of
      fusion of copolymers decreased by increasing the poly(propylene adipate) amount.
      The synthesized polymers exhibited low cytotoxicity and were used to encapsulate
      desferrioxamine, an iron-chelating drug. The desferrioxamine nanoparticles were
      self-assembled into core shell structures, had mean particle size <250 nm, and
      the drug remained in crystalline form. Further studies revealed that the
      dissolution rate was mainly related to the melting temperature, as well as to the
      degree of crystallinity of copolymers.

PMID- 22162655
TI  - A new era of cancer treatment: carbon nanotubes as drug delivery tools.
AB  - Cancer is a generic term that encompasses a group of diseases characterized by an
      uncontrolled proliferation of cells. There are over 200 different types of
      cancer, each of which gains its nomenclature according to the type of tissue the
      cell originates in. Many patients who succumb to cancer do not die as a result of
      the primary tumor, but because of the systemic effects of metastases on other
      regions away from the original site. One of the aims of cancer therapy is to
      prevent the metastatic process as early as possible. There are currently many
      therapies in clinical use, and recent advances in biotechnology lend credence to
      the potential of nanotechnology in the fight against cancer. Nanomaterials such
      as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties
      that can be exploited for diagnostic purposes, thermal ablation, and drug
      delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and
      axial symmetry, giving them unique properties that can be exploited in the
      diagnosis and treatment of cancer. In addition, CNTs have the potential to
      deliver drugs directly to targeted cells and tissues. Alongside the rapid
      advances in the development of nanotechnology-based materials, elucidating the
      toxicity of nanoparticles is also imperative. Hence, in this review, we seek to
      explore the biomedical applications of CNTs, with particular emphasis on their
      use as therapeutic platforms in oncology.

PMID- 22162657
TI  - Enhanced bioavailability of sirolimus via preparation of solid dispersion
      nanoparticles using a supercritical antisolvent process.
AB  - BACKGROUND: The aim of this study was to improve the physicochemical properties
      and bioavailability of poorly water-soluble sirolimus via preparation of a solid
      dispersion of nanoparticles using a supercritical antisolvent (SAS) process.
      METHODS: First, excipients for enhancing the stability and solubility of
      sirolimus were screened. Second, using the SAS process, solid dispersions of
      sirolimus-polyvinylpyrrolidone (PVP) K30 nanoparticles were prepared with or
      without surfactants such as sodium lauryl sulfate (SLS), tocopheryl propylene
      glycol succinate, Sucroester 15, Gelucire 50/13, and Myrj 52. A mean particle
      size of approximately 250 nm was obtained for PVP K30-sirolimus nanoparticles.
      Solid state characterization, kinetic solubility, powder dissolution, stability,
      and pharmacokinetics were analyzed in rats. RESULTS: X-ray diffraction,
      differential scanning calorimetry, and high-pressure liquid chromatography
      indicated that sirolimus existed in an anhydrous amorphous form within a solid
      dispersion of nanoparticles and that no degradation occurred after SAS
      processing. The improved supersaturation and dissolution of sirolimus as a solid
      dispersion of nanoparticles appeared to be well correlated with enhanced
      bioavailability of oral sirolimus in rats. With oral administration of a solid
      dispersion of PVP K30-SLS-sirolimus nanoparticles, the peak concentration and
      AUC(0->12h) of sirolimus were increased by approximately 18.3-fold and 15.2-fold,
      respectively. CONCLUSION: The results of this study suggest that preparation of
      PVP K30-sirolimus-surfactant nanoparticles using the SAS process may be a
      promising approach for improving the bioavailability of sirolimus.

PMID- 22162658
TI  - Interaction of an anticancer peptide fragment of azurin with p53 and its isolated
      domains studied by atomic force spectroscopy.
AB  - p28 is a 28-amino acid peptide fragment of the cupredoxin azurin derived from
      Pseudomonas aeruginosa that preferentially penetrates cancerous cells and arrests
      their proliferation in vitro and in vivo. Its antitumor activity reportedly
      arises from post-translational stabilization of the tumor suppressor p53 normally
      downregulated by the binding of several ubiquitin ligases. This would require p28
      to specifically bind to p53 to inhibit specific ligases from initiating
      proteosome-mediated degradation. In this study, atomic force spectroscopy, a
      nanotechnological approach, was used to investigate the interaction of p28 with
      full-length p53 and its isolated domains at the single molecule level. Analysis
      of the unbinding forces and the dissociation rate constant suggest that p28 forms
      a stable complex with the DNA-binding domain of p53, inhibiting the binding of
      ubiquitin ligases other than Mdm2 to reduce proteasomal degradation of p53.

PMID- 22162659
TI  - Evaluating the effects of crystallinity in new biocompatible polyester
      nanocarriers on drug release behavior.
AB  - Four new polyesters based on 1,3-propanediol and different aliphatic dicarboxylic
      acids were used to prepare ropinirole HCl-loaded nanoparticles. The novelty of
      this study lies in the use of polyesters with similar melting points but
      different degrees of crystallinity, varying from 29.8% to 67.5%, as drug
      nanocarriers. Based on their toxicity to human umbilical vein endothelial cells,
      these aliphatic polyesters were found to have cytotoxicity similar to that of
      polylactic acid and so may be considered as prominent drug nanocarriers. Drug
      encapsulation in polyesters was performed via an emulsification/solvent
      evaporation method. The mean particle size of drug-loaded nanoparticles was 164
      228 nm, and the drug loading content was 16%-23%. Wide angle X-ray diffraction
      patterns showed that ropinirole HCl existed in an amorphous state within the
      nanoparticle polymer matrices. Drug release diagrams revealed a burst effect for
      ropinirole HCl in the first 6 hours, probably due to release of drug located on
      the nanoparticle surface, followed by slower release. The degree of crystallinity
      of the host polymer matrix seemed to be an important parameter, because higher
      drug release rates were observed in polyesters with a low degree of
      crystallinity.

PMID- 22162660
TI  - Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis
      in ovo.
AB  - The objective of the study was to determine the effect of carbon nanoparticles
      produced by different methods on the growth of brain tumor and the development of
      blood vessels. Glioblastoma multiforme cells were cultured on the chorioallantoic
      membrane of chicken embryo and after 7 days of incubation, were treated with
      carbon nanoparticles administered in ovo to the tumor. Both types of
      nanoparticles significantly decreased tumor mass and volume, and vessel area.
      Quantitative real-time polymerase chain reaction analysis showed downregulated
      fibroblast growth factor-2 and vascular endothelial growth factor expression at
      the messenger ribonucleic acid level. The present results demonstrate
      antiangiogenic activity of carbon nanoparticles, making them potential factors
      for anticancer therapy.

PMID- 22162661
TI  - Hydrophobic ion pairing of an insulin-sodium deoxycholate complex for oral
      delivery of insulin.
AB  - Insulin was complexed with sodium deoxycholate to form an insulin-sodium
      deoxycholate complex (Ins-SD-Comp) using an hydrophobic ion pairing method in
      aqueous phase to enhance the liposolubility of insulin. In order to obtain the
      maximal complexation efficiency, the molar ratio of sodium deoxycholate to
      insulin was found. The zeta potential method was used to confirm the optimal
      ratio for formation of Ins-SD-Comp. The structural characteristics of Ins-SD-Comp
      were assessed using the Fourier transform infrared method. The apparent partition
      coefficient of insulin increased upon the formation of Ins-SD-Comp. Based on the
      preliminary study, Ins-SD-Comp was encapsulated into poly(lactide-co-glycolide)
      (PLGA) nanoparticles using an emulsion solvent diffusion method. The maximal
      encapsulation efficiency of Ins-SD-Comp into PLGA nanoparticles was 93.6% +/-
      2.81%, drug loading was about 4.8% +/- 0.32%, and the mean diameter of the
      nanoparticles was 278 +/- 13 nm. Biological activity and in vivo results revealed
      that the bioactivity of insulin was not destroyed during the preparation process.
      Ins-SD-Comp-loaded PLGA nanoparticles have the potential to reduce serum glucose
      levels and increase the oral bioavailability of insulin.

PMID- 22162663
TI  - Immune evasion strategies of Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is strongly correlated with chronic periodontitis. Its
      chronic persistence in the periodontium depends on its ability to evade host
      immunity without inhibiting the overall inflammatory response, which is actually
      beneficial for this and other periodontal bacteria. Indeed, the inflammatory
      exudate (gingival crevicular fluid) is a source of essential nutrients, such as
      peptides and hemin-derived iron. In this review, I discuss how P. gingivalis can
      promote its adaptive fitness through instigation of subversive crosstalk
      signaling. These interactions involve Toll-like receptor-2, complement receptor
      3, C5a anaphylatoxin receptor, and CXC-chemokine receptor 4. Their exploitation
      by P. gingivalis allows the pathogen to escape elimination, obtain nutrients, and
      collaterally inflict periodontal tissue injury.

PMID- 22162662
TI  - Electrostatic self-assembly of multilayer copolymeric membranes on the surface of
      porous tantalum implants for sustained release of doxorubicin.
AB  - Many studies in recent years have focused on surface engineering of implant
      materials in order to improve their biocompatibility and other performance.
      Porous tantalum implants have increasingly been used in implant surgeries, due to
      their biocompatibility, physical stability, and good mechanical strength. In this
      study we functionalized the porous tantalum implant for sustained drug delivery
      capability via electrostatic self-assembly of polyelectrolytes of hyaluronic
      acid, methylated collagen, and terpolymer on the surface of a porous tantalum
      implant. The anticancer drug doxorubicin was encapsulated into the multilayer
      copolymer membranes on the porous tantalum implants. Results showed the sustained
      released of doxorubicin from the functionalized porous tantalum implants for up
      to 1 month. The drug release solutions in 1 month all had inhibitory effects on
      the proliferation of chondrosarcoma cell line SW1353. These results suggest that
      this functionalized implant could be used in reconstructive surgery for the
      treatment of bone tumor as a local, sustained drug delivery system.

PMID- 22162664
TI  - Improving the catalytic activity of hyperthermophilic Pyrococcus horikoshii
      prolidase for detoxification of organophosphorus nerve agents over a broad range
      of temperatures.
AB  - Prolidases hydrolyze Xaa-Pro dipeptides and can also cleave the P-F and P-O bonds
      found in organophosphorus (OP) compounds, including the nerve agents soman and
      sarin. Ph1prol (PH0974) has previously been isolated and characterized from
      Pyrococcus horikoshii and was shown to have higher catalytic activity over a
      broader pH range, higher affinity for metal, and increased thermostability
      compared to P. furiosus prolidase, Pfprol (PF1343). To obtain a better enzyme for
      OP nerve agent decontamination and to investigate the structural factors that may
      influence protein thermostability and thermoactivity, randomly mutated Ph1prol
      enzymes were prepared. Four Ph1prol mutants (A195T/G306S-, Y301C/K342N-,
      E127G/E252D-, and E36V-Ph1prol) were isolated which had greater thermostability
      and improved activity over a broader range of temperatures against Xaa-Pro
      dipeptides and OP nerve agents compared to wild type Pyrococcus prolidases.

PMID- 22162665
TI  - Assembly of the complex between archaeal RNase P proteins RPP30 and Pop5.
AB  - RNase P is a highly conserved ribonucleoprotein enzyme that represents a model
      complex for understanding macromolecular RNA-protein interactions. Archaeal RNase
      P consists of one RNA and up to five proteins (Pop5, RPP30, RPP21, RPP29, and
      RPP38/L7Ae). Four of these proteins function in pairs (Pop5-RPP30 and RPP21
      RPP29). We have used nuclear magnetic resonance (NMR) spectroscopy and isothermal
      titration calorimetry (ITC) to characterize the interaction between Pop5 and
      RPP30 from the hyperthermophilic archaeon Pyrococcus furiosus (Pfu). NMR backbone
      resonance assignments of free RPP30 (25 kDa) indicate that the protein is well
      structured in solution, with a secondary structure matching that observed in a
      closely related crystal structure. Chemical shift perturbations upon the addition
      of Pop5 (14 kDa) reveal its binding surface on RPP30. ITC experiments confirm a
      net 1 : 1 stoichiometry for this tight protein-protein interaction and exhibit
      complex isotherms, indicative of higher-order binding. Indeed, light scattering
      and size exclusion chromatography data reveal the complex to exist as a 78 kDa
      heterotetramer with two copies each of Pop5 and RPP30. These results will inform
      future efforts to elucidate the functional role of the Pop5-RPP30 complex in
      RNase P assembly and catalysis.

PMID- 22162666
TI  - Factors affecting splicing strength of yeast genes.
AB  - Accurate and efficient splicing is of crucial importance for highly-transcribed
      intron-containing genes (ICGs) in rapidly replicating unicellular eukaryotes such
      as the budding yeast Saccharomyces cerevisiae. We characterize the 5' and 3'
      splice sites (ss) by position weight matrix scores (PWMSs), which is the highest
      for the consensus sequence and the lowest for splice sites differing most from
      the consensus sequence and used PWMS as a proxy for splicing strength. HAC1,
      which is known to be spliced by a nonspliceosomal mechanism, has the most
      negative PWMS for both its 5' ss and 3' ss. Several genes under strong splicing
      regulation and requiring additional splicing factors for their splicing also have
      small or negative PWMS values. Splicing strength is higher for highly transcribed
      ICGs than for lowly transcribed ICGs and higher for transcripts that bind
      strongly to spliceosomes than those that bind weakly. The 3' splice site features
      a prominent poly-U tract before the 3'AG. Our results suggest the potential of
      using PWMS as a screening tool for ICGs that are either spliced by a
      nonspliceosome mechanism or under strong splicing regulation in yeast and other
      fungal species.

PMID- 22162667
TI  - Treatment of Sexual-Orientation Obsessions in Obsessive-Compulsive Disorder Using
      Exposure and Ritual Prevention.
AB  - Presented is a case report of exposure and ritual prevention (EX/RP) therapy
      administered to a 51-year-old, White, heterosexual male with sexual-orientation
      obsessions in obsessive-compulsive disorder (OCD). The patient had been
      previously treated with pharmacotherapy, resulting in inadequate symptom
      reduction and unwanted side effects. OCD symptoms included anxiety about the
      possibility of becoming gay, mental reassurance, and avoidance of other men,
      which resulted in depressive symptoms and marital distress. The patient received
      17 EX/RP sessions, administered twice per week. The effect of treatment was
      evaluated using standardized rating instruments and self-monitoring by the
      patient. OCD symptoms on the Yale-Brown Obsessive Compulsive Scale (YBOCS) fell
      from 24 at intake to 3 at posttreatment and to 4 at a 6-week follow-up,
      indicating minimal symptoms. Improvement also occurred in mood, quality of life,
      and social adjustment. Issues concerning the assessment and treatment of
      homosexuality-themed obsessions in OCD are highlighted and discussed.

PMID- 22162668
TI  - Effects of Phosphorylation in Chlamydomonas Centrin Ser 167.
AB  - Centrin is a conserved calcium binding protein belonging to the EF-hand
      superfamily with two independent structural domains. This protein is found to be
      phosphorylated near the carboxyl terminal end. Our goal was to perform a novel
      comparative study of phosphorylated and unphosphorylated centrin by Fourier
      transform infrared (FT-IR) spectroscopy, two-dimensional correlation spectroscopy
      (2D-COS) analysis and differential scanning calorimetry (DSC). To achieve this
      goal, we have bacterially expressed, isolated, purified and phosphorylated
      centrin. We verified the extent of phosphorylation to be >97% for centrin by
      MALDI MS analysis and determined the absence of aggregated protein. The thermal
      denaturation temperature and DeltaCp were determined to be T(m) = 112.1  degrees
      C (DeltaCp = 7.8 Kcal/mole/DeltaC) and T(m) = 111.0 degrees C (DeltaCp = 5.0
      Kcal/mole/ degrees C) for holo-centrin and phosphorylated centrin, respectively.
      We have also described the molecular dynamics leading up to the thermal
      denaturation of the protein: for holo-centrin the vibrational modes associated
      with the calcium binding sites aspartates and glutamates, loops then the
      arginines, followed by the structured backbone vibrational modes the alpha-helix
      at 1635 cm(-1) then beta-sheet and finally the more exposed alpha-helix at 1650
      cm(-1); while for phosphorylated centrin aspartate, glutamate and arginine,
      followed by the backbone associated vibrational modes alpha-helix (1650 cm(-1)),
      loop then the beta-sheet (1633 cm(-1)) and finally the alpha-helix (1637 cm(-1)).
      Therefore, the effect on domain stability due to phosphorylation at Ser(167) was
      observed in the loops as well as the alpha-helix at 1650 cm(-1).

PMID- 22162670
TI  - Coal Depolymerising Activity and Haloperoxidase Activity of Mn Peroxidase from
      Fomes durissimus MTCC-1173.
AB  - Mn peroxidase has been purified to homogeneity from the culture filtrate of a new
      fungal strain Fomes durissimus MTCC-1173 using concentration by ultrafiltration
      and anion exchange chromatography on diethylaminoethyl (DEAE) cellulose. The
      molecular mass of the purified enzyme has been found to be 42.0 kDa using SDS
      PAGE analysis. The K(m) values using MnSO(4) and H(2)O(2) as the variable
      substrates in 50 mM lactic acid-sodium lactate buffer pH 4.5 at 30( degrees )C
      were 59 MUM and 32 MUM, respectively. The catalytic rate constants using MnSO(4)
      and H(2)O(2) were 22.4 s(-1) and 14.0 s(-1), respectively, giving the values of
      k(cat)/K(m) 0.38 MUM(-1)s(-1) and 0.44 MUM(-1)s(-1), respectively. The pH and
      temperature optima of the Mn peroxidase were 4 and 26( degrees )C, respectively.
      The purified MnP depolymerises humic acid in presence of H(2)O(2). The purified
      Mn peroxidase exhibits haloperoxidase activity at low pH.

PMID- 22162669
TI  - Synthesis and characterization of the ligand based on benzimidazole and its
      copper complex: DNA binding and antioxidant activity.
AB  - A new copper(II) complex with formulae of [Cu(buobb)(2)](pic)(2), where buobb
      stands for the ligand of 1,3-bis(1- butylbenzimidazol-2-yl)-2-oxopropane and pic
      represents 2,4,6-trinitrophenol, has been synthesized and characterized by
      elemental analyses, molar conductivity, IR, UV-Vis spectra measurements, and
      cyclic voltammetry. The crystal structure of the copper(II) complex has been
      determined by X-ray single-crystal diffraction. The coordination environment
      around each copper(II) atom can be described as a distorted octahedral geometry.
      The pi-pi stacking interactions link the copper(II) complex into a 1D infinite
      network. The interactions of the ligand and the copper(II) complex with calf
      thymus DNA (CT-DNA) are investigated by using electronic absorption titration,
      ethidium bromide-DNA displacement experiments, and viscosity measurements.
      Additionally, the copper(II) complex's antioxidant properties have been
      investigated in vitro.

PMID- 22162671
TI  - Structure and Properties of La(2)O(3)-TiO(2) Nanocomposite Films for Biomedical
      Applications.
AB  - The hemocompatibility of La(2)O(3)-doped TiO(2) films with different
      concentration prepared by radio frequency (RF) sputtering was studied. The
      microstructures and blood compatibility of TiO(2) films were investigated by scan
      electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and UV-visible
      optical absorption spectroscopy, respectively. With the increasing of the
      La(2)O(3) concentrations, the TiO(2) films become smooth, and the grain size
      becomes smaller. Meanwhile, the band gap of the samples increases from 2.85 to
      3.3 eV with increasing of the La(2)O(3) content in TiO(2) films from 0 to 3.64%.
      La(2)O(3)-doped TiO(2) films exhibit n-type semiconductor properties due to the
      existence of Ti(2+) and Ti(3+). The mechanism of hemocompatibility of TiO(2) film
      doped with La(2)O(3) was analyzed and discussed.

PMID- 22162672
TI  - Analysis of the release characteristics of cu-treated antimicrobial implant
      surfaces using atomic absorption spectrometry.
AB  - New developments of antimicrobial implant surfaces doped with copper (Cu) ions
      may minimize the risk of implant-associated infections. However, experimental
      evaluation of the Cu release is influenced by various test parameters. The aim of
      our study was to evaluate the Cu release characteristics in vitro according to
      the storage fluid and surface roughness. Plasma immersion ion implantation of Cu
      (Cu-PIII) and pulsed magnetron sputtering process of a titanium copper film (Ti
      Cu) were applied to titanium alloy (Ti6Al4V) samples with different surface
      finishing of the implant material (polished, hydroxyapatite and corundum
      blasted). The samples were submersed into either double-distilled water, human
      serum, or cell culture medium. Subsequently, the Cu concentration in the
      supernatant was measured using atomic absorption spectrometry. The test fluid as
      well as the surface roughness can alter the Cu release significantly, whereby the
      highest Cu release was determined for samples with corundum-blasted surfaces
      stored in cell medium.

PMID- 22162673
TI  - Central and Peripheral GABA(A) Receptor Regulation of the Heart Rate Depends on
      the Conscious State of the Animal.
AB  - Intuitively one might expect that activation of GABAergic inhibitory neurons
      results in bradycardia. In conscious animals the opposite effect is however
      observed. GABAergic neurons in nucleus ambiguus hold the ability to control the
      activity of the parasympathetic vagus nerve that innervates the heart. Upon GABA
      activation the vagus nerve will be inhibited leaving less parasympathetic impact
      on the heart. The picture is however blurred in the presence of anaesthesia where
      both the concentration and type of anaesthetics can result in different effects
      on the cardiovascular system. This paper reviews cardiovascular outcomes of GABA
      activation and includes own experiments on anaesthetized animals and isolated
      hearts. In conclusion, the impact of changes in GABAergic input is very difficult
      to predict in these settings, emphasizing the need for experiments performed in
      conscious animals when aiming at determining the cardiovascular effects of
      compounds acting on GABAergic neurons.

PMID- 22162674
TI  - A Comparison of the alpha2/3/5 Selective Positive Allosteric Modulators L-838,417
      and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain.
AB  - GABA(A) receptors containing alpha2/3 subunits are current targets in the battle
      to develop new pain medications, as they are expressed in the spinal cord where
      increasing inhibitory drive should result in analgesia. However, this approach is
      prone to a range of side effects including sedation, cognitive impairment, and
      abuse as a consequence of the widespread influence of GABA. The ability to make
      subtype selective low-efficacy benzodiazepine compounds, which potentiate the
      action of GABA at specific alpha subunits, has the potential to reduce this side
      effect profile. In this study, we have investigated the effects of the medium
      efficacy positive allosteric modulator (PAM) L-838,417 and the low-efficacy PAM
      TPA023 in a number of preclinical inflammatory and neuropathic pain models. We
      conclude that either the higher level of efficacy at alpha2/3 or efficacy at
      alpha5 is required for compounds to have a significant analgesic effect in a
      range of models, and, therefore, although the side-effect profile of compounds
      can be reduced compared to typical benzodiazepines, it is unlikely that it can be
      completely eliminated.

PMID- 22162675
TI  - Effects of grape seed extract, vitamin C, and vitamin e on ethanol- and aspirin
      induced ulcers.
AB  - Effects of GSE and vitamins C and E on aspirin- and ethanol-induced gastric ulcer
      and associated increases of lipid peroxidation in rats were compared. Two
      experiments were conducted. Rats were randomized into eight groups: a negative
      control and seven groups that received aspirin or ethanol for ulcer induction:
      one positive control (vehicle) and six with VC, VE, or GSE (25 and 250 mg/kg).
      Ulcer indexes and gastric levels of malondialdehyde (MDA) were quantified. VC,
      VE, and GSE (25 and 250 mg/kg) decreased aspirin, and ethanol-induced ulcers and
      MDA values compared with positive control group. The magnitude of aspirin ulcer
      reduction was comparable for all treatments, and MDA decrease with GSE was higher
      than with VC and tended to be greater, albeit none significantly, than with VE.
      GSE was more effective than VC and VE for lowering the ethanol ulcers, while the
      decrease of MDA levels with GSE was greater than with VC, but comparable to that
      achieved with VE. GSE protected against ethanol-induced gastric ulcers more
      effectively than VC or VE, while its protection against aspirin ulcers was
      comparable for all treatments. GSE produced the greatest reductions of gastric
      MDA in both models.

PMID- 22162676
TI  - The anti-inflammatory role of vitamin e in prevention of osteoporosis.
AB  - There is growing evidence that inflammation may be one of the causal factors of
      osteoporosis. Several cytokines such as IL-1, IL-6, RANKL, OPG, and M-CSF were
      implicated in the pathogenesis of osteoporosis. These cytokines are important
      determinants of osteoclast differentiation and its bone resorptive activity.
      Anticytokine therapy using cytokine antagonists such as IL-receptor antagonist
      and TNF-binding protein was able to suppress the activity of the respective
      cytokines and prevent bone loss. Several animal studies have shown that vitamin E
      in the forms of palm-derived tocotrienol and alpha-tocopherol may prevent
      osteoporosis in rat models by suppressing IL-1 and IL-6. Free radicals are known
      to activate transcription factor NFkappaB which leads to the production of bone
      resorbing cytokines. Vitamin E, a potent antioxidant, may be able to neutralise
      free radicals before they could activate NFkappaB, therefore suppressing cytokine
      production and osteoporosis. Vitamin E has also been shown to inhibit COX-2, the
      enzyme involved in inflammatory reactions. Of the two types of vitamin E studied,
      tocotrienol seemed to be better than tocopherol in terms of its ability to
      suppress bone-resorbing cytokines.

PMID- 22162677
TI  - Sedative and Hypnotic Activities of the Methanolic and Aqueous Extracts of
      Lavandula officinalis from Morocco.
AB  - We evaluate the sedative and hypnotic activities of the methanolic and aqueous
      extract of Lavandula officinalis L. on central nervous system (CNS). In this
      study, the effect of the methanolic and aqueous extracts of this plant was
      investigated in a battery of behavioural models in mice. Stems and flowers of
      Lavandula officinalis L. have several therapeutic applications in folk medicine
      in curing or managing a wide range of diseases, including insomnia. The
      methanolic extract produced significant sedative effect at the doses of 200, 400,
      and 600 mg/kg (by oral route), compared to reference substance diazepam (DZP),
      and an hypnotic effect at the doses of 800 and 1000 mg/kg while the treatment of
      mice with the aqueous extract at the doses of 200 and 400 mg/kg via oral pathway
      significantly reduced in both the reestablishment time and number of head dips
      during the traction and hole-board tests. In conclusion, these results suggest
      that the methanolic and aqueous extracts of Lavandula officinalis possess potent
      sedative and hypnotic activities, which supported its therapeutic use for
      insomnia.

PMID- 22162678
TI  - Dual implantation of artificial urinary sphincter and inflatable penile
      prostheses for concurrent male urinary incontinence and erectile dysfunction.
AB  - Erectile dysfunction and urinary incontinence secondary to sphincter dysfunction
      are common conditions affecting many men worldwide with a negative effect on
      quality of life. They are encountered in a number of etiologies most commonly
      following radical prostatectomy in which they coexist in the same patient.
      Implantations of an artificial urinary sphincter and inflatable penile prosthesis
      have proven to be effective in the treatment of both conditions should
      conservative and minimally invasive measures fail. The recent literature has
      shown that dual implantation of these devices is feasible and safe with a durable
      clinical outcome. Once indicated, this can be done in a synchronous or
      nonsynchronous manner; however, the emerging of the single transverse scrotal
      incision as well as advancement in the prostheses has made synchronous dual
      implantation more favourable and appealing option. It provides time and cost
      savings with an evidence of high patient satisfaction. Synchronous dual
      implantation should be offered initially when indicated. This paper discusses the
      surgical techniques of artificial urinary sphincter and inflatable penile
      prosthesis dual implantation in the management of concurrent moderate-to-severe
      urinary incontinence and medically refractive erectile dysfunction, in addition
      to highlighting the existing literature pertaining to this approach.

PMID- 22162679
TI  - Long-term followup after electrocautery transurethral resection of the prostate
      for benign prostatic hyperplasia.
AB  - Introduction. For decades, transurethral resection of the prostate (TURP) has
      been the "gold standard" operation for benign prostatic hyperplasia (BPH) but is
      based mainly on historic data. The historic data lacks use of validated measures
      and current TURP differs significantly from that performed 30 years ago. Methods.
      Men who had undergone TURP between 2001 and 2005 were reviewed. International
      prostate symptom score (IPSS), quality of life (QOL) and peak urinary flow rate
      (Q(max?)), and postvoid residual (PVR) were recorded. Operative details and
      postoperative complications were documented. Patients were then invited to attend
      for repeat assessment. Results. 91 patients participated. Mean follow-up time was
      70 months. Mean follow-up results were IPSS-7; QoL-1.5; Q(max?)-23 mL/s; PVR-45
      mL. These were an improvement from baseline of 67%, 63%, 187%, and 80%,
      respectively. Early complication rates were low, with no blood transfusions, TUR
      syndrome, or deaths occurring. Urethral stricture rate was higher than
      anticipated at 14%. Conclusion. This study shows modern TURP still produces
      durable improvement in voiding symptoms which remains comparable with historic
      studies. This study, however, found a marked drop in early complications but,
      conversely, a higher than expected incidence of urethral strictures.

PMID- 22162680
TI  - Urothelial Carcinoma of the Urinary Bladder in Young Adults: Presentation,
      Clinical behavior and Outcome.
AB  - Introduction. There is not much evidence regarding clinical behavior of bladder
      cancer in younger patients. We evaluated clinical characteristics, tumor
      recurrence and progression in patients younger than 40 years old with urothelial
      bladder carcinoma. Methods. We retrospectively reviewed the medical records of 31
      patients less than 40 years old who were firstly managed with bladder urothelial
      carcinoma in our department. Data were analysed with the Chi-square test.
      Results. Mean age was 31.7 years. Mean followup was 38.52 months (11-72 months).
      Nineteen (61%) patients were diagnosed with GII and 2 (6%) patients with GIII
      disease. Five (16%) patients presented with T1 disease. Three (9%) patients with
      invasive disease underwent cystectomy and adjuvant chemotherapy and one developed
      metastatic disease. Ten (32%) patients recurred during followup with a disease
      free recurrence rate of 65% the first 2 years after surgery. From those, 1
      patient progressed to higher stage and three to higher grade disease. No patient
      died during followup. Conclusions. Bladder urothelial carcinoma in patients
      younger than 40 years is usually low stage and low grade. Management of these
      patients should be according to clinical characteristics and no different from
      older patients with the same disease.

PMID- 22162681
TI  - Point-of-Care Tests for Bladder Cancer: The Influencing Role of Hematuria.
AB  - Introduction. Several point-of-care tests (POCT) are available for the diagnosis
      of bladder cancer (BC). We evaluate the impact of HU (hematuria) on performance
      of POCTs. Materials and Methods. Urine from 10 donors was diluted with blood from
      0.5 to 0.00625%. BladderCheck(R), BTAstat(R), BCM(R), and BTA(R) tests were
      applied. Tests were additionally conducted in 54 patients with HU. HU was
      stratified according to the amount of erythrocytes (RBC)/MUL using two systems:
      (1) no HU; mild microscopic HU; severe microscopic HU; gross HU; (2) I <25 RBCs;
      <250 II; >=250 III. Results were compared to HU status and histopathology.
      Results. Gross HU became evident between 2090 RBCs/MUL and 1065/MUL. Addition of
      blood led to default tests in all 4: BladderCheck(R) 0.25%; BCM 0.025%, BioNexia
      0.00625%, and BTAstat <0.00625%. Rates of false positives for BladderCheck,
      BTAstat, BCM, and BioNexia were 5.9, 11.8, 0, and 1.8% without HU and 0, 66.7,
      44.4, and 66.7% with HU. BTAstat, BCM, and BioNexia were independently influenced
      by HU (P < 0.0002). Conclusions. NMP22-BladderCheck was most resistant to blood.
      The diagnostic yield of all others was significantly influenced by HU. A well
      defined HU grading helps to define limits of HU for a reliable interpretation of
      BC-POCTs.

PMID- 22162683
TI  - Comparison of the Laryngeal View during Tracheal Intubation Using Airtraq and
      Macintosh Laryngoscopes by Unskillful Anesthesiology Residents: A Clinical Study.
AB  - Background and Objective. The Airtraq laryngoscope (Prodol Meditec, Vizcaya,
      Spain) is a novel tracheal intubation device. Studies, performed until now, have
      compared the Airtraq with the Macintosh laryngoscope, concluding that it reduces
      the intubation times and increase the success rate at first intubation attempt,
      decreasing the Cormack-Lehane score. The aim of the study was to evaluate if, in
      unskillful anesthesiology residents during the laryngoscopy, the Airtraq compared
      with the Macintosh laryngoscope improves the laryngeal view, decreasing the
      Cormack-Lehane score. Methods. A prospective, randomized, crossed-over trial was
      carried out on 60 patients. Each one of the patients were intubated using both
      devices by unskillful (less than two hundred intubations with the Macintosh
      laryngoscope and 10 intubations using the Airtraq) anesthesiology residents. The
      Cormack-Lehane score, the success rate at first intubation attempt, and the
      laryngoscopy and intubation times were compared. Results. The Airtraq
      significantly decreased the Cormack-Lehane score (P = 0.04). On the other hand,
      there were no differences in times of laryngoscopy (P = 0.645; IC 95% 3.1, +4.8)
      and intubation (P = 0.62; C95%  -6.1, +10.0) between the two devices. No relevant
      complications were found during the maneuvers of intubation using both devices.
      Conclusions. The Airtraq is a useful laryngoscope in unskillful anesthesiology
      residents improving the laryngeal view and, therefore, facilitating the tracheal
      intubation.

PMID- 22162684
TI  - Regional anesthesia in trauma medicine.
AB  - Regional anesthesia is an established method to provide analgesia for patients in
      the operating room and during the postoperative phase. While regional anesthesia
      offers unique advantages, as shown by the recent military experience, it is not
      commonly utilized in the prehospital or emergency department setting. Most often,
      regional anesthesia techniques for traumatized patients are first utilized in the
      operating room for procedural anesthesia or for postoperative pain control. While
      infiltration or single nerve block procedures are often used by surgeons or
      emergency medicine physicians in the preoperative phase, more advanced techniques
      such as plexus block procedures or regional catheter placements are more commonly
      performed by anesthesiologists for surgery or postoperative pain control. These
      regional techniques offer advantages over intravenous anesthesia, not just in the
      perioperative phase but also in the acute phase of traumatized patients and
      during the initial transport of injured patients. Anesthesiologists have
      extensive experience with regional techniques and are able to introduce regional
      anesthesia into settings outside the operating room and in the early treatment
      phases of trauma patients.

PMID- 22162682
TI  - A critical appraisal on the role of varicocele in male infertility.
AB  - Varicocele is a major cause of male infertility, as it may impair spermatogenesis
      through several distinct physiopathological mechanisms. With the recent advances
      in biomolecular techniques and the development of novel sperm functional tests,
      it has been possible to better understand the mechanisms involved in testicular
      damage provoked by varicocele and, therefore, propose optimized ways to prevent
      and/or reverse them. Up to now, there is still controversy involving the true
      benefit of varicocele repair in subfertile men as well as in certain specific
      situations such as concomitant contralateral subclinical varicocele or associated
      nonobstructive azoospermia. Also, with the continued development of assisted
      reproductive technology new issues and questions are emerging regarding the role
      of varicocelectomy in this context. This paper reviews the most recent data
      available on the pathogenesis, diagnosis, and management of varicocele with
      regard to male infertility.

PMID- 22162685
TI  - Pre-emptive treatment of lidocaine attenuates neuropathic pain and reduces pain
      related biochemical markers in the rat cuneate nucleus in median nerve chronic
      constriction injury model.
AB  - This study investigates the effects of lidocaine pre-emptive treatment on
      neuropathic pain behavior, injury discharges of nerves, neuropeptide Y (NPY) and
      c-Fos expression in the cuneate nucleus (CN) after median nerve chronic
      constriction injury (CCI). Behavior tests demonstrated that the pre-emptive
      lidocaine treatment dose dependently delayed and attenuated the development of
      mechanical allodynia within a 28-day period. Electrophysiological recording was
      used to examine the changes in injury discharges of the nerves. An increase in
      frequency of injury discharges was observed and peaked at postelectrical
      stimulation stage in the presaline group, which was suppressed by lidocaine pre
      emptive treatment in a dose-dependent manner. Lidocaine pretreatment also reduced
      the number of injury-induced NPY-like immunoreactive (NPY-LI) fibers and c-Fos-LI
      neurons within the CN in a dose-dependent manner. Furthermore, the mean number of
      c-Fos-LI neurons in the CN was significantly correlated to the NPY reduction
      level and the sign of mechanical allodynia following CCI.

PMID- 22162686
TI  - Age differences and changes in resources essential to aging well: a comparison of
      sexagenarians, octogenarians, and centenarians.
AB  - THIS STUDY EXAMINED CHANGE OVER TIME IN FIVE RESOURCES ASSESSED BY THE DUKE OARS
      MULTIDISCIPLINARY FUNCTIONAL ASSESSMENT QUESTIONNAIRE: social, economic, mental,
      physical, and functional resources. Two hundred and one participants in the
      Georgia Centenarian Study provided data for this longitudinal study: 70
      sexagenarians, 63 octogenarians, and 68 centenarians. Those in their 60s and 80s
      were followed up within 60 months; due to mortality attrition, centenarians were
      followed up within 20 months. Centenarians experienced the lowest levels of
      resources relative to those in their 80s and 60s. Over time they primarily
      experienced loss in activities of daily living, highlighting that the ability to
      maximize gains and mitigate losses over time for older adults is highly
      associated with various resources essential to well-being. Findings suggest that
      older adults'-especially the very old-resources should be concurrently assessed
      in a multidimensional analysis by researchers and practitioners who work with
      older adults in various settings.

PMID- 22162687
TI  - It takes a community to raise the prevalence of a zoonotic pathogen.
AB  - By definition, zoonotic pathogens are not strict host-species specialists in that
      they infect humans and at least one nonhuman reservoir species. The majority of
      zoonotic pathogens infect and are amplified by multiple vertebrate species in
      nature, each of which has a quantitatively different impact on the distribution
      and abundance of the pathogen and thus on disease risk. Unfortunately, when new
      zoonotic pathogens emerge, the dominant response by public health scientists is
      to search for a few, or even the single, most important reservoirs and to ignore
      other species that might strongly influence transmission. This focus on the
      single "primary" reservoir host species can delay biological understanding, and
      potentially public health interventions as species important in either amplifying
      or regulating the pathogen are overlooked. Investigating the evolutionary and
      ecological strategy of newly discovered or emerging pathogens within the
      community of potential and actual host species will be fruitful to both
      biological understanding and public health.

PMID- 22162688
TI  - Obstetric thromboprophylaxis: the Swedish guidelines.
AB  - Obstetric thromboprophylaxis is difficult. Since 10 years Swedish obstetricians
      have used a combined risk estimation model and recommendations concerning to
      whom, at what dose, when, and for how long thromboprophylaxis is to be
      administrated based on a weighted risk score. In this paper we describe the
      background and validation of the Swedish guidelines for obstetric
      thromboprophylaxis in women with moderate-high risk of VTE, that is, at similar
      or higher risk as the antepartum risk among women with history of thrombosis. The
      risk score is based on major risk factors (i.e., 5-fold increased risk of
      thromboembolism). We present data on the efficacy of the model, the cost
      effectiveness, and the lifestyle advice that is given. We believe that the
      Swedish guidelines for obstetric thromboprophylaxis aid clinicians in providing
      women at increased risk of VTE with effective and appropriate thromboprophylaxis,
      thus avoiding both over- and under-treatment.

PMID- 22162689
TI  - Heme Oxygenase-1: A Critical Link between Iron Metabolism, Erythropoiesis, and
      Development.
AB  - The first mature cells to arise in the developing mammalian embryo belong to the
      erythroid lineage. This highlights the immediacy of the need for red blood cells
      during embryogenesis and for survival. Linked with this pressure is the necessity
      of the embryo to obtain and transport iron, synthesize hemoglobin, and then
      dispose of the potentially toxic heme via the stress-induced protein heme
      oxygenase-1 (HO-1, encoded by Hmox1 in the mouse). Null mutation of Hmox1 results
      in significant embryonic mortality as well as anemia and defective iron
      recycling. Here, we discuss the interrelated nature of this critical enzyme with
      iron trafficking, erythroid cell function, and embryonic survival.

PMID- 22162690
TI  - Expression of thymidine phosphorylase in lymph nodes involved with mycosis
      fungoides and sezary syndrome.
AB  - Thymidine phosphorylase may be overexpressed in both neoplastic cells and tumor
      stromal cells in a variety of malignancies. Our study explores thymidine
      phosphorylase expression in lymph nodes (LNs) from patients with mycosis
      fungoides (MF) or Sezary syndrome (SS). In MF/SS, the LNs may have a pathologic
      diagnosis of either dermatopathic lymphadenopathy (LN-DL) or involvement by MF/SS
      (LN-MF). We performed immunohistochemical staining on MF/SS lymph nodes using
      antibodies to thymidine phosphorylase, CD68, CD21, CD3, and CD4. In both LN-DL
      and benign nodes, thymidine phosphorylase staining was noted only in macrophages,
      dendritic cells, and endothelial cells. In LN-MF, thymidine phosphorylase
      expression was also noted in subsets of intermediate to large neoplastic T cells.
      Concurrent CD68, CD21, CD3, and CD4 staining supported the above observations.
      Similar results were noted in the skin and in LN-MF with large cell
      transformation. Other T-cell lymphomas were also examined (total 7 cases); only
      enteropathy-type T-cell lymphoma (1 case) showed TP positivity in neoplastic T
      lymphocytes. We demonstrated that thymidine phosphorylase staining is present in
      neoplastic T cells in mycosis fungoides. The exact mechanism needs further
      investigation.

PMID- 22162691
TI  - Molecular targets for the treatment of juvenile myelomonocytic leukemia.
AB  - Significant advances in our understanding of the genetic defects and the
      pathogenesis of juvenile myelomonocytic leukemia (JMML) have been achieved in the
      last several years. The information gathered tremendously helps us in designing
      molecular targeted therapies for this otherwise fatal disease. Various approaches
      are being investigated to target defective pathways/molecules in this disease.
      However, effective therapy is still lacking. Development of specific target-based
      drugs for JMML remains a big challenge and represents a promising direction in
      this field.

PMID- 22162693
TI  - Cost effectiveness analysis of disease-modifying antirheumatic drugs in
      rheumatoid arthritis. A systematic review literature.
AB  - The cost effectiveness of treatments that have changed the "natural history" of a
      chronic progressive disease needs to be evaluated over the long term. Disease
      modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid
      arthritis (RA) and should be started as early as possible. A number of studies
      have shown that they are effective in improving disease activity and function,
      and in joint damage. Our review was focused on revision and critical evaluation
      of the studies including the literature on cost effectiveness of DMARDs
      (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European
      League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs
      are cost effective at the time of disease onset. They are less expensive than
      biological DMARDs and can be useful in controlling disease activity in early RA.

PMID- 22162692
TI  - A system out of breath: how hypoxia possibly contributes to the pathogenesis of
      systemic sclerosis.
AB  - Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular
      alterations and immunological disturbances and fibrosis, the order of which
      remains to be fully determined. Clinically, patients show clear signs of hypoxia
      in skin and internal organs. The low oxygen tension is potentially caused by a
      yet to be indentified circuitry involving the three features that typify SSc. In
      addition, once present, the hypoxia creates a vicious circle of ongoing
      pathology. In this paper, we provide an overview of the evidence that points
      towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how
      hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it
      is clear that hypoxia is an important hallmark in SSc patients. By providing an
      overview of the mechanisms at play and the possible therapeutic avenues that have
      emerged, we hope to stimulate researchers to provide novel clues into the
      conundrum in SSc patients.

PMID- 22162694
TI  - Closed reduction of bilateral posterior shoulder dislocation with medium
      impression defect of the humeral head: a case report and review of its treatment.
AB  - Bilateral dislocation of the shoulder is a rare injury. The main causes are
      electrical shock, extreme trauma, and epilepsy. A 25-year-old athletic-body man
      had sustained bilateral shoulder pain and restricted external rotation following
      electrical shock for five days. Although articular surface damage was about 50%
      in the right side and 30% in the left, it could be managed successfully by close
      reduction without pinning. During one-year follow-up, no recurrent dislocation or
      limitation of motion was seen. Closed management of medium size defect of the
      humeral head after posterior dislocation can be performed in cooperative and
      especially muscular patients.

PMID- 22162695
TI  - An unusual case of spontaneous bladder perforation with associated autodialysis
      of the ensuing urinary ascites.
AB  - Spontaneous rupture of the urinary bladder is a rare occurrence, and when
      encountered it is a diagnostic challenge. We present an unusual case of urinary
      bladder rupture in a patient with severe cerebral palsy who initially presented
      with localized abdominal pain and during admission developed generalized
      peritonitis caused by bladder rupture. In this case, the patient had none of risk
      factors associated with urinary bladder.

PMID- 22162696
TI  - Bipolar affective disorder and Parkinson's disease.
AB  - Little is known about comorbidities of bipolar disorder such as Parkinson's
      disease. A case history and a literature survey indicate that bipolar disorder is
      linked with or influences Parkinson's disease and vice versa. Underlying
      mechanisms are poorly understood, and, more importantly, no treatment options are
      established in such double diagnoses. The few data in comorbid Parkinson cases
      seem to point to a rapid cycling pattern of bipolar symptoms. With regard to
      therapeutic intervention, the literature supports pramipexole for treatment of
      both Parkinson and depressive symptoms in bipolar depression. Lithium, the mood
      stabilizer of choice for treating manic states, is problematical for use in
      Parkinson patients because of its side effects. Valproate might be an
      alternative, especially for treatment of rapid cycling.

PMID- 22162697
TI  - Malignant Hyperthermia and Idiopathic HyperCKemia.
AB  - Malignant hyperthermia (MH) is a rare but life-threatening condition that is more
      frequently encountered and discussed within the anesthesia literature. Here we
      through a case specifically discuss the susceptibility of individuals and/or
      families with asymptomatic unexplained elevations of creatine kinase (CK), also
      frequently referred to as hyperCKemia or idiopathic hyperCKemia (IHCK) in recent
      reports. The clinical implications would be to underscore the importance of this
      as a susceptibility to developing MH and highlight the importance of genetic
      susceptibility testing in such cases. Anesthesiologists and critical care
      intensivists as well as primary care physicians should keep this in mind when
      seeing patients with asymptomatic hyperCKemia and potentially inform them about
      the possibility of developing MH if exposed to triggering agents. Genetic
      susceptibility testing should be considered if available and family members
      should also receive nontriggering agents when undergoing anesthesia and wear
      Medic Alert tags.

PMID- 22162698
TI  - Recompensation of heart and kidney function after treatment with peritoneal
      dialysis in a case of congestive heart failure.
AB  - We report the case of a 57-year-old woman suffering from congestive heart
      failure. Due to refractory congestions despite optimised medical treatment, the
      patient was listed for heart transplantation and peritoneal dialysis was
      initiated. Peritoneal dialysis led to a significant weight loss, reduction of
      hyperhydration and extracellular water obtained by bioimpedance measurement, and
      a significant improvement in clinical and echocardiographic examination.
      Furthermore, residual kidney function increased during the long-term followup,
      and subsequently peritoneal dialysis was ceased. Pulmonary artery pressure and
      left ventricular ejection fraction remained stable and the patient did well. This
      case demonstrates the possibility of treating hyperhydration due to congestive
      heart failure with peritoneal dialysis resulting in recompensation of both heart
      and kidney functions.

PMID- 22162699
TI  - Cardiac arrest caused by multiple recurrent pulmonary embolism.
AB  - Pulmonary embolism is a common condition with a high mortality. We describe a
      previously healthy 68-year-old male who suffered three pulmonary embolisms during
      a short period of time, including two embolisms while on anticoagulant treatment.
      This paper illustrates three important points. (1) The importance of optimal
      anticoagulant treatment in the prevention of pulmonary embolism reoccurrence. (2)
      The benefit of immediate accessibility to echocardiography in the handling of
      haemodynamically unstable patients with an unknown underlying cause. (3)
      Thrombolytic treatment should always be considered and may be life-saving in
      patients with cardiac arrest suspected to be caused by pulmonary embolism.

PMID- 22162700
TI  - Exercise-induced hypoglycemic hemiplegia in a child with type 1 diabetes: a rare
      find with multiple potential causative mechanisms.
AB  - A 10-year-old boy known to have type 1 diabetes presented to the emergency
      department with history of sudden onset of right-sided hemiplegia after exercise.
      He did not respond to oral glucose administration, but had an almost immediate
      resolution of symptoms with intravenous bolus of dextrose. Hemiplegic
      hypoglycemia is a rare complication in diabetic children, mostly affects the
      right side of the body, and is rarely recurrent. Children have normal brain
      imaging and angiography testing, and electroencephalogram may show slow-wave
      activity. The recovery takes place within 24 hours, and the prognosis is
      excellent with no focal neurological deficits noted. Our patient responded within
      minutes to intravenous dextrose, which is unusual and has not been reported
      previously. The mechanisms leading to development of hypoglycemic hemiplegia are
      unclear, but may involve effects of hypoglycemia on intracellular signaling
      pathways or molecules on motor neurons, as recent studies have shown normal brain
      cell glucose uptake and metabolism in hypoglycemia. While hypoglycemic hemiplegia
      is rare, it is a frightening experience to caregivers, and efforts should
      concentrate on its prevention by preventing hypoglycemia.

PMID- 22162701
TI  - Homicide and associated steroid acute psychosis: a case report.
AB  - We report the case of an old man treated with methylprednisolone for chronic
      lymphoid leukemia. After two months of treatment, he declared an acute steroid
      psychosis and beat his wife to death. Steroids were stopped and the psychotic
      symptoms subsided, but his condition declined very quickly. The clinical course
      was complicated by a major depressive disorder with suicidal ideas, due to the
      steroid stoppage, the leukemia progressed, and by a sudden onset of a fatal
      pulmonary embolism. This clinical case highlights the importance of early
      detection of steroid psychosis and proposes, should treatment not be stopped, a
      strategy of dose reduction combined with a mood stabilizer or antipsychotic
      treatment. In addition have been revised the risks of the adverse psychiatric
      effects of steroids.

PMID- 22162702
TI  - Development of cutaneous leishmaniasis after leishmania skin test.
AB  - Thirty-year-old female with a previous history of a cutaneous ulcer suspicious of
      leishmaniasis 20 years ago presented with a new complaint of a depressed papular
      lesion 8 * 7 mm in the right lower extremity. The lesion was of 10-day duration.
      Because early cutaneous leishmaniasis (CL) lesions may have a non-ulcerated
      appearance, a Leishmania skin test (LST) was performed on the forearm with a
      strong positive result (38 * 32 mm). After 8 days, the lesion in the leg, which
      was diagnosed as folliculitis, completely healed. However, a typical CL ulcer (26
      * 24 mm) developed at the LST site. Histopathology of the new lesion did not
      identifiy parasites, but the findings were consistent with a diagnosis of CL.
      Further analysis identified amastigotes by immunohistochemical stain. Mononuclear
      cells harvested from the patient were stimulated with Leishmania antigen and
      showed high levels of production of both tumor necrosis factor-alpha (TNF-alpha)
      and interferon-gamma (IFN-gamma): 2,943 pg/mL and 2,313 pg/mL, respectively.
      After 40 days of treatment with antimony and pentoxifylline, the ulcer resolved.
      The development of CL at the LST site suggests a strong Th1 immune response, and
      it is an in vivo documentation of the role of the host immune response in the
      pathology of CL. It teaches us that LST should be cautiously, if at all, used in
      patients with self-healing CL ulcers.

PMID- 22162703
TI  - Polymyxin Combination Therapy and the Use of Serum Bactericidal Titers in the
      Management of KPC-Producing Klebsiella pneumoniae Infections: A Report of 3
      Cases.
AB  - Management of patients with KPC-harboring Enterobacteriaceae has become a
      significant and challenging scenario. We report three cases of KPC-producing
      Klebsiella pneumoniae bacteremia that were successfully treated using combination
      therapy with polymyxin B and other antimicrobials. Serum bactericidal titers were
      determined and provided additional clinical guidance in the management of such
      patients.

PMID- 22162704
TI  - Hypoacusia in a patient treated by isotretinoin.
AB  - Isotretinoin is the most effective treatment for severe acne, but there are
      several adverse effects associated with its use, some of them very exceptional
      (<1/10000). We report one case of hypoacusia and tinnitus in a 15-year-old boy
      treated with isotretinoin during 6 weeks, who quickly improved after isotretinoin
      withdrawal. Also, we comment other publications about hearing alterations in
      patients treated with isotretinoin and other retinoids.

PMID- 22162705
TI  - Septic mesenteric venous thrombophlebitis: a rare complication of acute
      appendicitis.
AB  - Mesenteric venous thrombophlebitis represents a very rare complication of acute
      appendicitis. Based on the findings of a 45-year-old patient with mesenteric
      venous thrombophlebitis due to acute appendicitis, we herein describe the
      diagnostic difficulties and therapeutic options in this uncommon disease. The
      treatment in our case consisted of simple appendectomy and perioperative
      anticoagulation therapy.

PMID- 22162706
TI  - Electrocardiographic characteristics of ventricular arrhythmia originating from
      the left coronary cusp.
AB  - Aortic cusps originating arrhythmias are rare; they have special
      electrocardiogram features that help to locate the site of origin. We report on a
      20-year-old male patient without structural heart disease presenting with
      accelerated idioventricular rhythm; electrocardiogram analysis was typical of
      left coronary cusp origin.

PMID- 22162707
TI  - L-carnitine improves the asthma control in children with moderate persistent
      asthma.
AB  - The objective. was to investigate L-Carnitine level and the effects of its
      supplementation in children with moderate persistent Asthma. Methods. Free and
      total serum carnitine levels were measured in 50 children having moderate
      persistent asthma and 50 healthy control children. The patients group was
      randomly divided into two subgroups. Subgroup A was supplemented with L-carnitine
      for 6 months while subgroup B was used as a placebo controls. Both subgroups were
      assessed by pulmonary function tests (PFT) and childhood-asthma control test (C
      ACT) before and 6 months after carnitine supplementation. Results. Total and free
      carnitine levels were significantly lower in patient group than in control group.
      PFT and C-ACT showed significant improvements in asthmatic children supplemented
      with L-carnitine than in those who were not supplemented. Conclusion. L-carnitine
      levels were initially lower in moderate persistent asthmatic children as compared
      to healthy control children. Asthmatic children who received L-carnitine
      supplementation showed statistically significant improvement of C-ACT and PFT.

PMID- 22162708
TI  - Environmental effects on fractional exhaled nitric oxide in allergic children.
AB  - Fractional exhaled nitric oxide (FeNO) is a non-invasive marker of airway
      inflammation in asthma and respiratory allergy. Environmental factors, especially
      indoor and outdoor air quality, may play an important role in triggering acute
      exacerbations of respiratory symptoms. The authors have reviewed the literature
      reporting effects of outdoor and indoor pollutants on FeNO in children. Although
      the findings are not consistent, urban and industrial pollution-mainly particles
      (PM(2.5) and PM(10)), nitrogen dioxide (NO(2)), and sulfur dioxide (SO(2))-as
      well as formaldehyde and electric baseboard heating have been shown to increase
      FeNO, whilst ozone (O(3)) tends to decrease it. Among children exposed to
      Environmental Tobacco Smoke (ETS) with a genetic polymorphisms in nitric oxide
      synthase genes (NOS), a higher nicotine exposure was associated with lower FeNO
      levels. Finally, although more studies are needed in order to better investigate
      the effect of gene and environment interactions which may affect the
      interpretation of FeNO values in the management of children with asthma,
      clinicians are recommended to consider environmental exposures when taking
      medical histories for asthma and respiratory allergy. Further research is also
      needed to assess the effects of remedial interventions aimed at reducing/abating
      environmental exposures in asthmatic/allergic patients.

PMID- 22162709
TI  - Conversion of tumors into autologous vaccines by intratumoral injection of alpha
      Gal glycolipids that induce anti-Gal/alpha-Gal epitope interaction.
AB  - Anti-Gal is the most abundant antibody in humans, constituting 1% of
      immunoglobulins. Anti-Gal binds specifically alpha-gal epitopes (Galalpha1
      3Galbeta1-4GlcNAc-R). Immunogenicity of autologous tumor associated antigens
      (TAA) is greatly increased by manipulating tumor cells to express alpha-gal
      epitopes and bind anti-Gal. Glycolipids with alphagal epitopes (alpha-gal
      glycolipids) injected into tumors insert into the tumor cell membrane. Anti-Gal
      binding to the multiple alpha-gal epitopes de novo presented on the tumor cells
      results in targeting of these cells to APC via the interaction between the Fc
      portion of the bound anti-Gal and Fcgamma; receptors on APC. The APC process and
      present immunogenic TAA peptides and thus, effectively activate tumor specific
      CD4+ helper T cells and CD8+ cytotoxic T cells which destroy tumor cells in
      micrometastases. The induced immune response is potent enough to overcome
      immunosuppression by Treg cells. A phase I clinical trial indicated that alpha
      gal glycolipid treatment has no adverse effects. In addition to achieving
      destruction of micrometastases in cancer patients with advance disease, alpha-gal
      glycolipid treatment may be effective as neo-adjuvant immunotherapy. Injection of
      alpha-gal glycolipids into primary tumors few weeks prior to resection can induce
      a protective immune response capable of destroying micrometastases expressing
      autologous TAA, long after primary tumor resection.

PMID- 22162710
TI  - Immune microenvironment in colorectal cancer: a new hallmark to change old
      paradigms.
AB  - Impact of immune microenvironment in prognosis of solid tumors has been
      extensively studied in the last few years. Specifically in colorectal carcinoma,
      increased knowledge of the immune events around these tumors and their relation
      with clinical outcomes have led to consider immune microenvironment as one of the
      most important prognostic factors in this disease. In this review we will
      summarize and update the current knowledge with respect to this intriguing and
      complex new hallmark of cancer, paying special attention to infiltration by T
      infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its
      eventual clinical translation in terms of long-term prognosis. Finally, we
      suggest some possible investigational approaches based on combinatorial
      strategies to trigger and boost immune reaction against tumor cells.

PMID- 22162711
TI  - The confluence of stereotactic ablative radiotherapy and tumor immunology.
AB  - Stereotactic radiation approaches are gaining more popularity for the treatment
      of intracranial as well as extracranial tumors in organs such as the liver and
      lung. Technology, rather than biology, is driving the rapid adoption of
      stereotactic body radiation therapy (SBRT), also known as stereotactic ablative
      radiotherapy (SABR), in the clinic due to advances in precise positioning and
      targeting. Dramatic improvements in tumor control have been demonstrated;
      however, our knowledge of normal tissue biology response mechanisms to large
      fraction sizes is lacking. Herein, we will discuss how SABR can induce cellular
      expression of MHC I, adhesion molecules, costimulatory molecules, heat shock
      proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors
      to enhance antitumor immune responses.

PMID- 22162713
TI  - HLA class II defects in Burkitt lymphoma: bryostatin-1-induced 17 kDa protein
      restores CD4+ T-cell recognition.
AB  - While the defects in HLA class I-mediated Ag presentation by Burkitt lymphoma
      (BL) have been well documented, CD4+ T-cells are also poorly stimulated by HLA
      class II Ag presentation, and the reasons underlying this defect(s) have not yet
      been fully resolved. Here, we show that BL cells are deficient in their ability
      to optimally stimulate CD4+ T cells via the HLA class II pathway. The observed
      defect was not associated with low levels of BL-expressed costimulatory
      molecules, as addition of external co-stimulation failed to result in BL-mediated
      CD4+ T-cell activation. We further demonstrate that BL cells express the
      components of the class II pathway, and the defect was not caused by faulty
      Ag/class II interaction, because antigenic peptides bound with measurable
      affinity to BL-associated class II molecules. Treatment of BL with broystatin-1,
      a potent modulator of protein kinase C, led to significant improvement of
      functional class II Ag presentation in BL. The restoration of immune recognition
      appeared to be linked with an increased expression of a 17 kDa peptidylprolyl
      like protein. These results demonstrate the presence of a specific defect in HLA
      class II-mediated Ag presentation in BL and reveal that treatment with bryostatin
      1 could lead to enhanced immunogenicity.

PMID- 22162712
TI  - Tumor cells and tumor-associated macrophages: secreted proteins as potential
      targets for therapy.
AB  - Inflammatory pathways, meant to defend the organism against infection and injury,
      as a byproduct, can promote an environment which favors tumor growth and
      metastasis. Tumor-associated macrophages (TAMs), which constitute a significant
      part of the tumor-infiltrating immune cells, have been linked to the growth,
      angiogenesis, and metastasis of a variety of cancers, most likely through
      polarization of TAMs to the M2 (alternative) phenotype. The interaction between
      tumor cells and macrophages provides opportunities for therapy. This paper will
      discuss secreted proteins as targets for intervention.

PMID- 22162714
TI  - Dietary supplementation with omega-3-PUFA-rich fish oil reduces signs of food
      allergy in ovalbumin-sensitized mice.
AB  - We investigated the effect of dietary supplementation with n-3 PUFA (fish oil
      source) in an experimental model of food allergy. Mice were sensitized (allergic
      group) or not (nonallergic group) with OVA and were fed with OVA diet to induce
      allergy signals. Mice were fed with regular diet in which 7% of lipid content was
      provided by soybean (5% of n-3 PUFA) or fish (25% of n-3 PUFA) oil. Allergic
      group mice had increased serum levels of antiovalbumin IgE and IgG1 and changes
      in small intestine, characterized by an increased edema, number of rolling
      leukocytes in microcirculation, eosinophil infiltration, mucus production, and
      Paneth cell degranulation, in comparison to non-allergic group. All these
      inflammatory parameters were reduced in mice fed high-n-3-PUFA diet. Our data
      together suggest that diet supplementation with n-3 PUFA from fish oil may
      consist of a valid adjuvant in food allergy treatment.

PMID- 22162715
TI  - Induction of immunological tolerance by oral anti-CD3.
AB  - In recent years, our knowledge about immunoregulation and autoimmunity has
      significantly advanced, but nontoxic and more effective treatments for different
      inflammatory and autoimmune diseases are still lacking. Oral tolerance is of
      unique immunologic importance because it is a continuous natural immunologic
      event driven by exogenous antigen and is an attractive approach for treatment of
      these conditions. Parenteral administration of anti-CD3 monoclonal antibody is an
      approved therapy for transplantation in humans and is effective in autoimmune
      diabetes. Orally administered anti-CD3 monoclonal antibody is biologically active
      in the gut and suppresses experimental models of autoimmune diseases. Orally
      delivered antibody does not have side effects including cytokine release
      syndromes, thus oral anti-CD3 antibody is clinically applicable for chronic
      therapy. Here we review findings that identify a novel and powerful immunologic
      approach that is widely applicable for the treatment of human autoimmune
      conditions.

PMID- 22162716
TI  - Mesangial cell-specific antibodies are central to the pathogenesis of lupus
      nephritis.
AB  - Not only is nephritis a common complaint in systemic lupus erythematosus, but it
      is also the most life-threatening complication of the disease. Anti-double
      stranded DNA antibodies (Abs), which are found in up to 80% of these patients,
      might be nephritogenic per se. That is, they may cross-react with mesangial cell
      (MC) surface proteins, such as alpha-actinin and annexin A2, they may cross-react
      with mesangial matrix protein such as laminine and fibronectin, or they may
      recognize chromatin material previously deposited in the glomeruli. The
      consequence of the binding of anti-MC Abs may be their internalization, which
      results in activation and proliferation of these MCs. In turn, these activated
      MCs are suspected of promoting immune complex formation by sequestering and
      thereby protecting chromatin from degradation. The present paper will explain the
      mechanisms through which such autoAbs may initiate nephritis.

PMID- 22162717
TI  - Bartonella infection in immunocompromised hosts: immunology of vascular infection
      and vasoproliferation.
AB  - Most infections by genus Bartonella in immunocompromised patients are caused by
      B. henselae and B. quintana. Unlike immunocompetent hosts who usually develop
      milder diseases such as cat scratch disease and trench fever, immunocompromised
      patients, including those living with HIV/AIDS and posttransplant patients, are
      more likely to develop different and severe life-threatening disease. This paper
      will discuss Bartonella's manifestations in immunosuppressed patients and will
      examine Bartonella's interaction with the immune system including its mechanisms
      of establishing infection and immune escape. Gaps in current understanding of the
      immunology of Bartonella infection in immunocompromised hosts will be
      highlighted.

PMID- 22162718
TI  - Regulatory T cells accumulate in the lung allergic inflammation and efficiently
      suppress T-cell proliferation but not Th2 cytokine production.
AB  - Foxp3(+)CD25(+)CD4(+) regulatory T cells are vital for peripheral tolerance and
      control of tissue inflammation. In this study, we characterized the phenotype and
      monitored the migration and activity of regulatory T cells present in the airways
      of allergic or tolerant mice after allergen challenge. To induce lung allergic
      inflammation, mice were sensitized twice with ovalbumin/aluminum hydroxide gel
      and challenged twice with intranasal ovalbumin. Tolerance was induced by oral
      administration of ovalbumin for 5 consecutive days prior to OVA sensitization and
      challenge. We detected regulatory T cells (Foxp3(+)CD25(+)CD4(+) T cells) in the
      airways of allergic and tolerant mice; however, the number of regulatory T cells
      was more than 40-fold higher in allergic mice than in tolerant mice. Lung
      regulatory T cells expressed an effector/memory phenotype
      (CCR4(high)CD62L(low)CD44(high)CD54(high)CD69(+)) that distinguished them from
      naive regulatory T cells (CCR4(int)CD62L(high)CD44(int)CD54(int)CD69(-)). These
      regulatory T cells efficiently suppressed pulmonary T-cell proliferation but not
      Th2 cytokine production.

PMID- 22162720
TI  - Mapping of minimal motifs of B-cell epitopes on human zona pellucida glycoprotein
      3.
AB  - The human zona pellucida glycoprotein-3 (hZP3) by virtue of its critical role
      during fertilization has been proposed as a promising candidate antigen to
      develop a contraceptive vaccine. In this direction, it is imperative to map
      minimal motifs of the B cell epitopes (BCEs) so as to avoid ZP-specific
      oophoritogenic T cell epitopes (TCEs) in the ZP3-based immunogens. In this study,
      based on known results of mapping marmoset and bonnet monkey ZP3 (mstZP3 and
      bmZP3), two predictable epitopes(23-30  and  301-320) on hZP3 were first
      confirmed and five minimal motifs within four epitopes on hZP3 were defined using
      serum to recombinant hZP3a(22-176) or hZP3b(177-348) as well as a biosynthetic
      peptide strategy. These defined minimal motifs were QPLWLL(23-28) for hZP3(23
      30), MQVTDD(103-108) for hZP3(93-110), EENW(178-181) for hZP3(172-190), as well
      as SNSWF(306-310) and EGP(313-315) for hZP3(301-320), respectively. Furthermore,
      the antigenicity of two peptides for hZP3(172-187) and hZP3(301-315) and
      specificity of the antibody response to these peptides were also evaluated, which
      produced high-titer antibodies in immunized animals that were capable of reacting
      to ZP on human oocytes, r-hZP3b(177-348) protein, as well as r-hZP3(172-190), r
      hZP3(303-310), and r-hZP3(313-320) epitope peptides fused with truncated GST188
      protein.

PMID- 22162722
TI  - Follicle structure influences the availability of oxygen to the oocyte in antral
      follicles.
AB  - The ability of an oocyte to successfully mature is highly dependent on
      intrafollicular conditions, including the size and structure of the follicle.
      Here we present a mathematical model of oxygen transport in the antral follicle.
      We relate mean oxygen concentration in follicular fluid of bovine follicles to
      the concentration in the immediate vicinity of the cumulus-oocyte complex (COC).
      The model predicts that the oxygen levels within the antral follicle are
      dependent on the size and structure of the follicle and that the mean level of
      dissolved oxygen in follicular fluid does not necessarily correspond to that
      reaching the COC.

PMID- 22162719
TI  - Shining a light on intestinal traffic.
AB  - Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative
      colitis, is associated with enhanced leukocyte infiltration to the gut, which is
      directly linked to the clinical aspects of these disorders. Thus, leukocyte
      trafficking is a major target for IBD therapy. Past and emerging techniques to
      study leukocyte trafficking both in vitro and in vivo have expanded our knowledge
      of the leukocyte migration process and the role of inhibitors. Various strategies
      have been employed to target chemokine- and integrin-ligand interactions within
      the multistep adhesion cascade and the S1P/S1PR1 axis in leukocyte migration.
      Though there is an abundance of preclinical data demonstrating efficacy of
      leukocyte trafficking inhibitors, many have yet to be confirmed in clinical
      studies. Vigilance for toxicity and further research is required into this
      complex and emerging area of IBD therapy.

PMID- 22162723
TI  - Modeling and representation of human hearts for volumetric measurement.
AB  - This paper investigates automatic construction of a three-dimensional heart model
      from a set of medical images, represents it in a deformable shape, and uses it to
      perform volumetric measurements. This not only significantly improves its
      reliability and accuracy but also makes it possible to derive valuable novel
      information, like various assessment and dynamic volumetric measurements. The
      method is based on a flexible model trained from hundreds of patient image sets
      by a genetic algorithm, which takes advantage of complete segmentation of the
      heart shape to form a geometrical heart model. For an image set of a new patient,
      an interpretation scheme is used to obtain its shape and evaluate some important
      parameters. Apart from automatic evaluation of traditional heart functions, some
      new information of cardiovascular diseases may be recognized from the volumetric
      analysis.

PMID- 22162721
TI  - Advances in our understanding of the pathogenesis of HIV-1 associated nephropathy
      in children.
AB  - Childhood HIV-1 associated nephropathy (HIVAN) is a clinical and renal
      histological disease characterized by heavy proteinuria associated with focal and
      segmental glomerular sclerosis and/or mesangial hyperplasia in combination with
      microcystic tubular dilatation. These lesions lead to renal enlargement and rapid
      progression to kidney failure. Children of African ancestry have a unique
      susceptibility to developing HIVAN. It is estimated that approximately 300,000
      HIV-infected children living in the sub-Saharan Africa could develop HIVAN if
      they do not receive appropriate antiretroviral therapy. This article discusses
      recent developments and controversies related to the pathogenesis of childhood
      HIVAN. The role of host genetic factors, including the newly identified variants
      in the APOL1 gene, is discussed in the context of previous studies that
      established the pathological paradigm for HIVAN, and our current understanding of
      the functional genomics analysis. Hopefully, these advances will provide new
      research opportunities to generate better treatments for children with HIVAN.

PMID- 22162724
TI  - Modeling of biological intelligence for SCM system optimization.
AB  - This article summarizes some methods from biological intelligence for modeling
      and optimization of supply chain management (SCM) systems, including genetic
      algorithms, evolutionary programming, differential evolution, swarm intelligence,
      artificial immune, and other biological intelligence related methods. An SCM
      system is adaptive, dynamic, open self-organizing, which is maintained by flows
      of information, materials, goods, funds, and energy. Traditional methods for
      modeling and optimizing complex SCM systems require huge amounts of computing
      resources, and biological intelligence-based solutions can often provide valuable
      alternatives for efficiently solving problems. The paper summarizes the recent
      related methods for the design and optimization of SCM systems, which covers the
      most widely used genetic algorithms and other evolutionary algorithms.

PMID- 22162726
TI  - Cancer, stem cells and cancer stem cells: old ideas, new developments.
AB  - It has been suggested that, at least in some forms of cancer, a sub-population of
      slow-cycling, therapy-resistant cancer stem cells exists that has the ability to
      reconstitute the tumor in its entirety. If true, this model implies that
      conventional therapies based on targeting highly cycling cells within the tumor
      will leave the slow-cycling stem cell population intact, giving them the
      opportunity to reinitiate the tumor at a later date. This review discusses the
      evidence for this model and the likely implications for cancer treatment.

PMID- 22162725
TI  - Motion analysis of live objects by super-resolution fluorescence microscopy.
AB  - Motion analysis plays an important role in studing activities or behaviors of
      live objects in medicine, biotechnology, chemistry, physics, spectroscopy,
      nanotechnology, enzymology, and biological engineering. This paper briefly
      reviews the developments in this area mostly in the recent three years,
      especially for cellular analysis in fluorescence microscopy. The topic has
      received much attention with the increasing demands in biomedical applications.
      The tasks of motion analysis include detection and tracking of objects, as well
      as analysis of motion behavior, living activity, events, motion statistics, and
      so forth. In the last decades, hundreds of papers have been published in this
      research topic. They cover a wide area, such as investigation of cell, cancer,
      virus, sperm, microbe, karyogram, and so forth. These contributions are
      summarized in this review. Developed methods and practical examples are also
      introduced. The review is useful to people in the related field for easy referral
      of the state of the art.

PMID- 22162727
TI  - Alzheimer's - Looking beyond plaques.
AB  - Mounting evidence shows that inflammation plays a critical role in causing
      Alzheimer's disease. Over the last few decades we have gone from a situation
      where inflammation was generally believed to have no role in the disease to the
      current picture where chronic activation of IL-1 inflammation has been shown to
      account for many of the hallmarks of the disease. This review is a personal
      account of the quest to prove that inflammation plays a critical role in causing
      Alzheimer's disease.

PMID- 22162728
TI  - The puzzling origin of the autophagosomal membrane.
AB  - Autophagy is one of the newest and fastest emerging research areas in biomedical
      life sciences. Autophagosomes, large double-membrane vesicles enclosing
      cytoplasmic components targeted for degradation, are the hallmark of this
      catabolic pathway. The origin of the lipid bilayers composing these transport
      carriers has been the central enigma of the field since the discovery of
      autophagy. A series of recent studies has implicated several cellular organelles
      as the possible source of the autophagosomal membranes, if anything further
      clouding our view. In this compendium, we will discuss these apparently
      contradictory results and briefly emphasize the relevance of determining the
      lipid source used for autophagy for future translational research, for example in
      drug discovery programs.

PMID- 22162730
TI  - Unusual case of hypomagnesaemia induced seizures.
AB  - Alterations in electrolyte homeostasis associated with major surgery and critical
      illness are common but usually non-specific. We report an unusual case of
      hypomagnesaemia induced seizures in a 73-year-old woman who was recovering from
      ileal resection and limited right hemicolectomy for small bowel volvulus.
      Hypomagnesaemia as a de novo cause of seizures is rarely reported.

PMID- 22162729
TI  - Structure and recognition of polyubiquitin chains of different lengths and
      linkage.
AB  - The polyubiquitin signal is post-translationally attached to a large number of
      proteins, often directing formation of macromolecular complexes resulting in the
      translocation, assembly or degradation of the attached protein. Recent structural
      and functional studies reveal general mechanisms by which different architectures
      and length of the signal are distinguished.

PMID- 22162731
TI  - New onset of multiple keratoacanthomas and palmoplantar hyperkeratosis caused by
      the treatment of metastatic renal cell carcinoma with a new generation multi
      kinase inhibitor.
AB  - The use of new generation multi-kinase inhibitors for the treatment of various
      malignancies has brought unique and previously unrecognised cutaneous reactions
      to the attention of dermatologists. We report the case of a patient with
      metastatic renal cell carcinoma who presented to our dermatology clinic with
      eruptive squamous cell carcinomas with keratoacanthomatous features and painless
      palmoplantar hyperkeratosis while taking sorafenib (Nexavar). Dermatological
      toxicity from sorafenib has been well described in the literature. Herein we
      describe a combination of unusual symptoms due to sorafenib.

PMID- 22162732
TI  - A rare case of acute abdomen.
AB  - Mesenteric cysts are tumoural formations which are generally benign in character,
      originate from the intestinal mesentery, and rarely cause abdominal tumours. They
      are asymptomatic unless a complication occurs, and thus may be incidentally
      diagnosed. Symptomatic cases may show up with findings such as abdominal pain,
      abdominal mass, nausea, and vomiting, and sometimes patients present with an
      acute abdomen. Treatment includes total excision of the cyst. We present the case
      of a male patient admitted to our emergency department with acute abdominal
      symptoms, who was subsequently found to have a mesenteric cyst measuring 30*20*9
      cm.

PMID- 22162733
TI  - Emphysematous cystitis: radiological diagnosis of complicated urinary tract
      infection.
AB  - Emphysematous cystitis is an uncommon condition characterised by the presence of
      gas in the bladder. It is an infection caused by gas forming organisms, usually
      in elderly women with a background of diabetes mellitus. The presentation is
      variable, however with increasing use of imaging more cases are being diagnosed
      in asymptomatic patients. Routine cross-sectional imaging is not advocated for
      specific diagnosis but its role in accurate assessment of the severity of the
      condition cannot be overlooked. As the mode and duration of follow-up in
      incidentally detected cases has not been addressed in the literature, follow-up
      should be tailored individually depending upon the severity and response to
      treatment. We describe two such incidentally detected cases of emphysematous
      cystitis in elderly diabetic patients and present a review of the literature. The
      triad of treatment is adequate control of diabetes, antibiotics and bladder
      drainage. One patient died in the hospital, while the other underwent a flexible
      cystoscopy 6 weeks later which was normal.

PMID- 22162734
TI  - Retroperitoneal leiomyomata as a cause of bilateral hydronephrosis and
      lumbosciatic pain.
AB  - Leiomyomas can occasionally be found in the pelvic and/or abdominal parietal
      retroperitoneum. This rare entity is known as retroperitoneal leiomyomata. We
      report the case of a 46-year-old female with bilateral hydronephrosis and chronic
      sciatic pain caused by invasive retroperitoneal leiomyoma 3 years after
      hysterectomy, and a successful outcome after treatment with surgery followed by
      aromatase inhibitors to control pelvic residual disease. Aromatase inhibitors
      could be a satisfactory treatment option after surgery to control retroperitoneal
      leiomyoma residual disease.

PMID- 22162735
TI  - A case of small cell carcinoma of the oesophagus treated with endoscopic mucosal
      resection who remained in clinical remission for 18 months: its endoscopic
      features with specific light spectra.
AB  - Small cell carcinoma of the oesophagus (SCCE) is an infrequent tumour associated
      with a poor prognosis. We herein propose the first case of SCCE treated by
      endoscopic mucosal resection (EMR) and its endoscopic images with narrow band
      imaging (NBI) and autofluorescence imaging (AFI). A 63-year-old man complained of
      a loss of appetite. An upper endoscopic examination revealed a 7 mm nodule
      located 33 cm from the incisors. A weakly stained area was shown by iodine
      staining. NBI detected brownish amorphous dots with irregular vessels on the
      surface of the nodule and AFI distinctly embossed the lesion magenta. A biopsy
      specimen obtained from the lesions revealed typical SCCE. The patient underwent
      EMR to remove the SCCE and thereafter remained in a state of clinical remission
      for 18 months. In summary, NBI and AFI may be useful for detecting and
      differentially diagnosing SCCE from the squamous cell carcinoma of the
      oesophagus. EMR is therefore considered to be a potentially useful therapeutic
      option for removing SCCE instead of performing an oesophagotomy.

PMID- 22162736
TI  - A case of vitiligo vulgaris showing a pronounced improvement after treatment for
      myasthenia gravis.
AB  - This is a report of a 64 year-old male patient whose myasthenia gravis (MG) was
      accompanied by vitiligo vulgaris. Depigmentation of the face, trunk, and hands
      was noted. He was diagnosed with vitiligo vulgaris according to macroscopic
      findings and a skin biopsy. He was also found to have blepharoptosis, and
      proximal dominant muscle weakness of the extremities. He was anti-acetylcholine
      receptor antibody-positive, with repetitive nerve stimulation showing a waning
      phenomenon and chest computed tomography showing invasive thymoma, which led to
      the diagnosis of generalised MG. His myasthenic symptoms were relieved by the use
      of steroids and the removal of the thymoma. His vitiligo vulgaris began to
      improve a month after the relief of myasthenic symptoms. Such improvement was
      pronounced during the next several months. The clinical or immunological
      relationship between MG and vitiligo vulgaris is still not known, but these
      findings might indicate clinical correlation between MG and vitiligo vulgaris.

PMID- 22162737
TI  - Lung injury and renal failure caused by potassium cyanide poisoning.
AB  - Our objective is to show that cyanide poisoning presents with various symptoms,
      and that recognition of these symptoms is required for appropriate management of
      the condition. A 54-year-old man drank about 2.5 times the normal fatal dose of
      potassium cyanide in a suicide attempt. On arrival at hospital (day 0), the
      patient was restless and in a state of shock. We administered 100% oxygen and
      performed immediate detoxification. Ground-glass attenuation appeared on the
      evening of day 1 and lung injury due to cyanide was suspected. Inflammation
      improved slowly with the use of artificial ventilation, but anuria continued and
      sudden renal failure occurred on day 2. We suspected that renal failure was due
      to cyanide metabolites, and continuous haemodiafiltration (CHDF) was initiated.
      Renal function improved slowly and CHDF was discontinued on the sixth day.
      Symptoms of cyanide poisoning may include lung injury and renal damage, in
      addition to disturbance of consciousness.

PMID- 22162738
TI  - Incidental finding of Castleman's disease in an asymptomatic young adult.
AB  - Castleman's disease (CD) is a rare lymphoproliferative disorder of unknown
      aetiology presenting with different clinical manifestations in young adults.
      There are two main types, unicentric occurring in a younger age group and
      multicentric occurring in older people. We report the case of 22-year-old man who
      initially presented with acute appendicitis. During his admission he had a
      routine chest radiograph which demonstrated a mass lesion, later diagnosed as
      Castleman's disease of hyaline vascular type. He underwent a right pneumonectomy
      for complete excision and made an unremarkable recovery.

PMID- 22162739
TI  - Atypical cause of prolonged myelosuppression.
AB  - We present the case of a 57-year-old male with poor prognosis (trisomy 21 and
      monosomy 7) acute myeloid leukaemia (AML) who presented with rigors and fever
      during cytogenetic remission. Peripheral and central line blood cultures were
      positive for Mycobacterium chelonae and he commenced empiric treatment with
      meropenem, amikacin, clarithromycin and ciprofloxacin. It appears that M chelonae
      infection was responsible for persistent myelosuppression after expected recovery
      from chemotherapy, which subsequently precluded optimum treatment for AML.

PMID- 22162740
TI  - Initial presentation of childhood leukaemia with facial palsy: three case
      reports.
AB  - Acute lymphoblastic leukaemia and acute myeloblastic leukaemia are the most
      common malignancies diagnosed in children. Facial palsy is an acute peripheral
      palsy involving the facial nerve and is an unusual presentation of childhood
      acute leukaemia. We present three cases (a 9-year-old boy, a 14-year-old boy and
      a 10-year-old boy) of acute leukaemia with initial presentation of facial palsy.
      It is important for physicians to recognise the neurological manifestations of
      childhood leukaemia and extensive work-up should be carried out to exclude
      secondary causes of facial palsy.

PMID- 22162741
TI  - An unusual presentation of non-small cell lung carcinoma.
AB  - Lung cancer is the most common malignancy in the Western world and usually
      presents with respiratory symptoms. The diagnosis of lung cancer is normally made
      by chest radiography followed by histological confirmation with either
      radiological or endoscopically guided biopsies. Very rarely, imaging does not
      help with the initial diagnosis. Haematuria is a common presentation and
      generally requires urological follow-up with radiological and cystoscopic
      examination. The differential diagnosis includes urothelial and renal cancers. We
      present the case of a patient who initially presented to urologists with
      haematuria and was thought to have a urological malignancy. Contrast enhanced
      computerised tomography (CT) of both the chest and abdomen after initial
      endoscopic examination was non-diagnostic. It was only laparoscopic removal of
      enlarged para-aortic lymph nodes which ultimately provided the diagnosis of non
      small cell lung carcinoma.

PMID- 22162742
TI  - A Gaussian Copula Model for Multivariate Survival Data.
AB  - We consider a Gaussian copula model for multivariate survival times. Estimation
      of the copula association parameter is easily implemented with existing software
      using a two-stage estimation procedure. Using the Gaussian copula, we are able to
      test whether the association parameter is equal to zero. When the association
      term is positive, the model can be extended to incorporate cluster-level frailty
      terms. Asymptotic properties are derived under the two-stage estimation scheme.
      Simulation studies verify finite sample utility. We apply the method to a
      Children's Oncology Group multi-center study of acute lymphoblastic leukemia. The
      analysis estimates marginal treatment effects and examines potential clustering
      within treatment institution.

PMID- 22162743
TI  - Risk-specific optimal cancer screening schedules: an application to breast cancer
      early detection.
AB  - The optimal schedules for breast cancer screening in terms of examination
      frequency and ages at examination are of practical interest. A decision-theoretic
      approach is explored to search for optimal cancer screening programs which should
      achieve maximum survival benefit while balancing the associated cost to the
      health care system. We propose a class of utility functions that account for
      costs associated with screening examinations and value of survival benefit under
      a non-stable disease model. We consider two different optimization criteria:
      optimize the number of screening examinations with equal screening intervals
      between exams but without a pre-fixed total cost; and optimize the ages at which
      screening should be given for a fixed total cost. We show that an optimal
      solution exists under each of the two frameworks. The proposed methods may
      consider women at different levels of risk for breast cancer so that the optimal
      screening strategies will be tailored according to a woman's risk of developing
      the disease. Results of a numerical study are presented and the proposed models
      are illustrated with various data inputs. We also use the data inputs from the
      Health Insurance Plan of New York (HIP) and Canadian National Breast Screening
      Study (CNBSS) to illustrate the proposed models and to compare the utility values
      between the optimal schedules and the actual schedules in the HIP and CNBSS
      trials. Here, the utility is defined as the difference in cure rates between
      cases found at screening examinations and cases found between screening
      examinations while accounting for the cost of examinations, under a given
      screening schedule.

PMID- 22162744
TI  - Progress in the development of new therapies for herpesvirus  infections.
AB  - Resurgent interest in antiviral drugs for the treatment of herpesvirus has led to
      the development of new compounds that are progressing through clinical trials.
      This is important because there are few therapeutic options for resistant
      infections and some viruses such as human cytomegalovirus remain underserved. New
      compounds include conventional DNA polymerase inhibitors such as valomaciclovir
      and cyclopropavir, as well as CMX001 that has a broad spectrum of antiviral
      activity that includes all the herpesviruses. It also includes compounds with new
      molecular targets such as maribavir (MBV), FV-100, AIC361, and AIC246. Recent
      advances with each of these compounds will be reviewed including their virus
      specificity, mechanism of action, and stage of development. The potential of
      these new compounds to improve clinical outcome will also be discussed.

PMID- 22162745
TI  - A Machine-Learning Approach to Detecting Unknown Bacterial Serovars.
AB  - Technologies for rapid detection of bacterial pathogens are crucial for securing
      the food supply. A light-scattering sensor recently developed for real-time
      identification of multiple colonies has shown great promise for distinguishing
      bacteria cultures. The classification approach currently used with this system
      relies on supervised learning. For accurate classification of bacterial
      pathogens, the training library should be exhaustive, i.e., should consist of
      samples of all possible pathogens. Yet, the sheer number of existing bacterial
      serovars and more importantly the effect of their high mutation rate would not
      allow for a practical and manageable training. In this study, we propose a
      Bayesian approach to learning with a nonexhaustive training dataset for automated
      detection of unmatched bacterial serovars, i.e., serovars for which no samples
      exist in the training library. The main contribution of our work is the Wishart
      conjugate priors defined over class distributions. This allows us to employ the
      prior information obtained from known classes to make inferences about unknown
      classes as well. By this means, we identify new classes of informational value
      and dynamically update the training dataset with these classes to make it
      increasingly more representative of the sample population. This results in a
      classifier with improved predictive performance for future samples. We evaluated
      our approach on a 28-class bacteria dataset and also on the benchmark 26-class
      letter recognition dataset for further validation. The proposed approach is
      compared against state-of-the-art involving density-based approaches and support
      vector domain description, as well as a recently introduced Bayesian approach
      based on simulated classes.

PMID- 22162746
TI  - Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID
      mice.
AB  - Current treatments for HBV chronic carriers using interferon alpha or nucleoside
      analogues are not effective in all patients and may induce the emergence of HBV
      resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine
      family, inhibits HBV replication by destabilizing capsid assembly. The aim of
      this study was to determine the antiviral effect of Bay 41-4109 in a mouse model
      with humanized liver and the spread of active HBV. Antiviral assays of Bay 41
      4109 on HepG2.2.15 cells constitutively expressing HBV, displayed an IC(50) of
      about 202 nM with no cell toxicity. Alb-uPA/SCID mice were transplanted with
      human hepatocytes and infected with HBV. Ten days post-infection, the mice were
      treated with Bay 41-4109 for five days. During the 30 days of follow-up, the HBV
      load was evaluated by quantitative PCR. At the end of treatment, decreased HBV
      viremia of about 1 log(10) copies/ml was observed. By contrast, increased HBV
      viremia of about 0.5 log(10) copies/ml was measured in the control group. Five
      days after the end of treatment, a rebound of HBV viremia occurred in the treated
      group. Furthermore, 15 days after treatment discontinuation, a similar expression
      of the viral capsid was evidenced in liver biopsies. Our findings demonstrate
      that Bay 41-4109 displayed antiviral properties against HBV in humanized Alb
      uPA/SCID mice and confirm the usefulness of Alb-uPA/SCID mice for the evaluation
      of pharmaceutical compounds. The administration of Bay 41-4109 may constitute a
      new strategy for the treatment of patients in escape from standard antiviral
      therapy.

PMID- 22162747
TI  - Actin-independent behavior and membrane deformation exhibited by the four
      transmembrane protein M6a.
AB  - M6a is a four-transmembrane protein that is abundantly expressed in the nervous
      system. Previous studies have shown that over-expression of this protein induces
      various cellular protrusions, such as neurites, filopodia, and dendritic spines.
      In this detailed characterization of M6a-induced structures, we found their
      varied and peculiar characteristics. Notably, the M6a-induced protrusions were
      mostly devoid of actin filaments or microtubules and exhibited free random
      vibrating motion. Moreover, when an antibody bound to M6a, the membrane-wrapped
      protrusions were suddenly disrupted, leading to perturbation of the surrounding
      membrane dynamics involving phosphoinositide signaling. During single-molecule
      analysis, M6a exhibited cytoskeleton-independent movement and became selectively
      entrapped along the cell perimeter in an actin-independent manner. These
      observations highlight the unusual characteristics of M6a, which may have a
      significant yet unappreciated role in biological systems.

PMID- 22162748
TI  - Active transport of bile acids decreases mucin 2 in neonatal ileum: implications
      for development of necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of
      premature infants, but its etiology remains unclear. We have previously shown
      that mucin 2 (Muc2) positive goblet cells are significantly decreased in NEC. We
      have also shown that ileal bile acids (BAs) are significantly increased during
      the development of this disease. Because BAs can affect mucins, we hypothesized
      that elevated ileal BAs contribute to decreased Muc2 in experimental NEC. The
      role of Muc2 in NEC was evaluated in Winnie +/+ mice, a strain that produces
      aberrant Muc2. Muc2 and trefoil factor 3 (Tff3) were assessed in neonatal rats
      subjected to the NEC protocol when bile acids were removed, and in ileal explants
      from newborn and older rats cultured with and without BAs. Further, the role of
      active transport of BAs was determined using neonatal rats given the apical
      sodium dependent bile acid transporter (Asbt) inhibitor SC-435 and in neonatal
      Asbt knockout mice subjected to the NEC protocol. Mice with aberrant Muc2 had
      significantly greater incidence and severity of NEC. Using both in vivo and ex
      vivo techniques, we determined that BAs decrease Muc2 positive cells in neonatal
      but not older ileum. However, Tff3 positive cells are not decreased by BAs. In
      addition, active transport of BAs is required for BAs to decrease Muc2 in
      immature ileum. These data show that functional Muc2 plays a critical role in the
      prevention of NEC and BAs can potentiate the decreased Muc2 in disease
      development. Further, BAs have a more profound effect on Muc2 in immature versus
      older ileum, which may explain at least in part why NEC occurs almost exclusively
      in premature infants.

PMID- 22162749
TI  - Genomes and virulence factors of novel bacterial pathogens causing bleaching
      disease in the marine red alga Delisea pulchra.
AB  - Nautella sp. R11, a member of the marine Roseobacter clade, causes a bleaching
      disease in the temperate-marine red macroalga, Delisea pulchra. To begin to
      elucidate the molecular mechanisms underpinning the ability of Nautella sp. R11
      to colonize, invade and induce bleaching of D. pulchra, we sequenced and analyzed
      its genome. The genome encodes several factors such as adhesion mechanisms,
      systems for the transport of algal metabolites, enzymes that confer resistance to
      oxidative stress, cytolysins, and global regulatory mechanisms that may allow for
      the switch of Nautella sp. R11 to a pathogenic lifestyle. Many virulence
      effectors common in phytopathogenic bacteria are also found in the R11 genome,
      such as the plant hormone indole acetic acid, cellulose fibrils, succinoglycan
      and nodulation protein L. Comparative genomics with non-pathogenic Roseobacter
      strains and a newly identified pathogen, Phaeobacter sp. LSS9, revealed a patchy
      distribution of putative virulence factors in all genomes, but also led to the
      identification of a quorum sensing (QS) dependent transcriptional regulator that
      was unique to pathogenic Roseobacter strains. This observation supports the model
      that a combination of virulence factors and QS-dependent regulatory mechanisms
      enables indigenous members of the host alga's epiphytic microbial community to
      switch to a pathogenic lifestyle, especially under environmental conditions when
      innate host defence mechanisms are compromised.

PMID- 22162750
TI  - Structure of the Bro1 domain protein BROX and functional analyses of the ALIX
      Bro1 domain in HIV-1 budding.
AB  - BACKGROUND: Bro1 domains are elongated, banana-shaped domains that were first
      identified in the yeast ESCRT pathway protein, Bro1p. Humans express three Bro1
      domain-containing proteins: ALIX, BROX, and HD-PTP, which function in association
      with the ESCRT pathway to help mediate intraluminal vesicle formation at
      multivesicular bodies, the abscission stage of cytokinesis, and/or enveloped
      virus budding. Human Bro1 domains share the ability to bind the CHMP4 subset of
      ESCRT-III proteins, associate with the HIV-1 NC(Gag) protein, and stimulate the
      budding of viral Gag proteins. The curved Bro1 domain structure has also been
      proposed to mediate membrane bending. To date, crystal structures have only been
      available for the related Bro1 domains from the Bro1p and ALIX proteins, and
      structures of additional family members should therefore aid in the
      identification of key structural and functional elements. METHODOLOGY/PRINCIPAL
      FINDINGS: We report the crystal structure of the human BROX protein, which
      comprises a single Bro1 domain. The Bro1 domains from BROX, Bro1p and ALIX adopt
      similar overall structures and share two common exposed hydrophobic surfaces.
      Surface 1 is located on the concave face and forms the CHMP4 binding site,
      whereas Surface 2 is located at the narrow end of the domain. The structures
      differ in that only ALIX has an extended loop that projects away from the convex
      face to expose the hydrophobic Phe105 side chain at its tip. Functional studies
      demonstrated that mutations in Surface 1, Surface 2, or Phe105 all impair the
      ability of ALIX to stimulate HIV-1 budding. CONCLUSIONS/SIGNIFICANCE: Our studies
      reveal similarities in the overall folds and hydrophobic protein interaction
      sites of different Bro1 domains, and show that a unique extended loop contributes
      to the ability of ALIX to function in HIV-1 budding.

PMID- 22162751
TI  - Phasevarion mediated epigenetic gene regulation in Helicobacter pylori.
AB  - Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes)
      that are subject to phase-variable expression (high-frequency reversible ON/OFF
      switching of gene expression). In Haemophilus influenzae and pathogenic
      Neisseria, the random switching of the modA gene, associated with a phase
      variable type III restriction modification (R-M) system, controls expression of a
      phase-variable regulon of genes (a "phasevarion"), via differential methylation
      of the genome in the modA ON and OFF states. Phase-variable type III R-M systems
      are also found in Helicobacter pylori, suggesting that phasevarions may also
      exist in this key human pathogen. Phylogenetic studies on the phase-variable type
      III modH gene revealed that there are 17 distinct alleles in H. pylori, which
      differ only in their DNA recognition domain. One of the most commonly found
      alleles was modH5 (16% of isolates). Microarray analysis comparing the wild-type
      P12modH5 ON strain to a P12DeltamodH5 mutant revealed that six genes were either
      up- or down-regulated, and some were virulence-associated. These included flaA,
      which encodes a flagella protein important in motility and hopG, an outer
      membrane protein essential for colonization and associated with gastric cancer.
      This study provides the first evidence of this epigenetic mechanism of gene
      expression in H. pylori. Characterisation of H. pylori modH phasevarions to
      define stable immunological targets will be essential for vaccine development and
      may also contribute to understanding H. pylori pathogenesis.

PMID- 22162752
TI  - BAD modulates counterregulatory responses to hypoglycemia and protective
      glucoprivic feeding.
AB  - Hypoglycemia or glucoprivation triggers protective hormonal counterregulatory and
      feeding responses to aid the restoration of normoglycemia. Increasing evidence
      suggests pertinent roles for the brain in sensing glucoprivation and mediating
      counterregulation, however, the precise nature of the metabolic signals and
      molecular mediators linking central glucose sensing to effector functions are not
      fully understood. Here, we demonstrate that protective hormonal and feeding
      responses to hypoglycemia are regulated by BAD, a BCL-2 family protein with dual
      functions in apoptosis and metabolism. BAD-deficient mice display impaired
      glycemic and hormonal counterregulatory responses to systemic glucoprivation
      induced by 2-deoxy-D-glucose. BAD is also required for proper counterregulatory
      responses to insulin-induced hypoglycemia as evident from significantly higher
      glucose infusion rates and lower plasma epinephrine levels during
      hyperinsulinemic hypoglycemic clamps. Importantly, RNA interference-mediated
      acute knockdown of Bad in the brain provided independent genetic evidence for its
      relevance in central glucose sensing and proper neurohumoral responses to
      glucoprivation. Moreover, BAD deficiency is associated with impaired glucoprivic
      feeding, suggesting that its role in adaptive responses to hypoglycemia extends
      beyond hormonal responses to regulation of feeding behavior. Together, these data
      indicate a previously unappreciated role for BAD in the control of central
      glucose sensing.

PMID- 22162753
TI  - Investigations on the usefulness of CEACAMs as potential imaging targets for
      molecular imaging purposes.
AB  - Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs) family
      are the prototype of tumour markers. Classically they are used as serum markers,
      however, CEACAMs could serve as targets for molecular imaging as well.In order to
      test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM
      expression was analysed using this antibody. Twelve human cancer cell lines from
      different entities were screened for their CEACAM expression using qPCR, Western
      Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary
      tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM
      mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines
      showed the highest expression levels with good correlation of mRNA and protein
      level. However, when grown in vivo, the CEACAM expression was generally
      downregulated except for the melanoma cell lines. As the CEACAM expression showed
      pronounced expression in FemX-1 primary tumours, this model system was used for
      further experiments. As the accessibility of the antibody after i.v. application
      is critical for its use in molecular imaging, the binding of the T84.1 monoclonal
      antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1
      primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to
      tumour cells in the vicinity of blood vessels. This binding pattern was
      particularly pronounced in the periphery of the tumour xenograft, however, some
      antibody binding was also observed in the central areas of the tumour around
      blood vessels. Still, a general penetration of the tumour by i.v. application of
      the anti CEACAM antibody could not be achieved despite homogenous CEACAM
      expression of all melanoma cells when analysed in tissue sections. This lack of
      penetration is probably due to the increased interstitial fluid pressure in
      tumours caused by the absence of functional lymphatic vessels.

PMID- 22162754
TI  - Expansion of genes encoding piRNA-associated argonaute proteins in the pea aphid:
      diversification of expression profiles in different plastic morphs.
AB  - Piwi-interacting RNAs (piRNAs) are known to regulate transposon activity in germ
      cells of several animal models that propagate sexually. However, the role of
      piRNAs during asexual reproduction remains almost unknown. Aphids that can
      alternate sexual and asexual reproduction cycles in response to seasonal changes
      of photoperiod provide a unique opportunity to study piRNAs and the piRNA pathway
      in both reproductive modes. Taking advantage of the recently sequenced genome of
      the pea aphid Acyrthosiphon pisum, we found an unusually large lineage-specific
      expansion of genes encoding the Piwi sub-clade of Argonaute proteins. In situ
      hybridisation showed differential expressions between the duplicated piwi copies:
      while Api-piwi2 and Api-piwi6 are "specialised" in germ cells their most closely
      related copy, respectively Api-piwi5 and Api-piwi3, are expressed in the somatic
      cells. The differential expression was also identified in duplicated ago3: Api
      ago3a in germ cells and Api-ago3b in somatic cells. Moreover, analyses of
      expression profiles of the expanded piwi and ago3 genes by semi-quantitative RT
      PCR showed that expressions varied according to the reproductive types. These
      specific expression patterns suggest that expanded aphid piwi and ago3 genes have
      distinct roles in asexual and sexual reproduction.

PMID- 22162755
TI  - Do cues matter? Highly inductive settlement cues don't ensure high post
      settlement survival in sea urchin aquaculture.
AB  - Increasing settlement and post-settlement survival during the critical transition
      from planktonic larvae to benthic juveniles will increase efficiency for sea
      urchin aquaculture. This study investigated the effects of temperature and
      settlement cues on the settlement and post-settlement survival of the sea urchin
      Tripneustes gratilla during this phase. The current commercial methodology, which
      utilises natural biofilm settlement plates, was tested and resulted in low
      settlement (<2%) and poor post-settlement survival (<1% of settled urchins). In
      laboratory trials, settlement was high and unaffected by temperatures between 24
      and 30 degrees C, but significantly decreased at 33 degrees C. Development of
      spines, however, was significantly affected by temperatures over 29 degrees C.
      Mirroring this result, post-settlement survival was optimal between 24-28 degrees
      C. In laboratory assays, the macroalgae Sargassum linearifolium and Corallina
      officinalis, and seawater conditioned with these algae, induced significantly
      higher settlement (>90%) than a natural biofilm (~25%). The addition of
      macroalgae-conditioned seawater to natural biofilm significantly increased
      settlement rates (>85%). Mixed consortia and single strains of bacteria isolated
      from macroalgae, biofilms and adult conspecifics all induced significant
      settlement, but at significantly lower rates than macroalgae. No evidence was
      found that higher rates of settlement to bacteria on macroalgae were generated by
      a cofactor from the macroalgae. Age of bacterial cultures, culturing bacteria on
      solid and liquid media and concentration of nutrients in cultures had little
      effect on settlement rates. Finally, macroalgae-conditioned seawater combined
      with natural biofilm settlement plates induced significantly higher settlement
      than to the biofilm plates alone in a commercial scale trial. However, high post
      settlement mortality resulted in equivalent survival between treatments after 25
      days. This study highlights that settlement studies should extend to post
      settlement survival, which remains poor for T. gratilla and is a significant
      obstacle to increasing efficiency for aquaculture.

PMID- 22162756
TI  - Evidence of dopaminergic processing of executive inhibition.
AB  - Inhibition of unwanted response is an important function of the executive system.
      Since the inhibitory system is impaired in patients with dysregulated dopamine
      system, we examined dopamine neurotransmission in the human brain during
      processing of a task of executive inhibition. The experiment used a recently
      developed dynamic molecular imaging technique to detect and map dopamine released
      during performance of a modified Eriksen's flanker task. In this study, young
      healthy volunteers received an intravenous injection of a dopamine receptor
      ligand ((11)C-raclopride) after they were positioned in the PET camera. After the
      injection, volunteers performed the flanker task under Congruent and Incongruent
      conditions in a single scan session. They were required to inhibit competing
      options to select an appropriate response in the Incongruent but not in the
      Congruent condition. The PET data were dynamically acquired during the experiment
      and analyzed using two variants of the simplified reference region model. The
      analysis included estimation of a number of receptor kinetic parameters before
      and after initiation of the Incongruent condition. We found increase in the rate
      of ligand displacement (from receptor sites) and decrease in the ligand binding
      potential in the Incongruent condition, suggesting dopamine release during task
      performance. These changes were observed in small areas of the putamen and
      caudate bilaterally but were most significant on the dorsal aspect of the body of
      left caudate. The results provide evidence of dopaminergic processing of
      executive inhibition and demonstrate that neurochemical changes associated with
      cognitive processing can be detected and mapped in a single scan session using
      dynamic molecular imaging.

PMID- 22162757
TI  - BCG induces protection against Mycobacterium tuberculosis infection in the Wistar
      rat model.
AB  - Our understanding of the correlation of Mycobacterium bovis Bacille Calmette
      Guerin (BCG)-mediated immune responses and protection against Mycobacterium
      tuberculosis (Mtb) infection is still limited. We have recently characterized a
      Wistar rat model of experimental tuberculosis (TB). In the present study, we
      evaluated the efficacy of BCG vaccination in this model. Upon Mtb challenge, BCG
      vaccinated rats controlled growth of the bacilli earlier than unvaccinated rats.
      Histopathology analysis of infected lungs demonstrated a reduced number of
      granulomatous lesions and lower parenchymal inflammation in vaccinated animals.
      Vaccine-mediated protection correlated with the rapid accumulation of antigen
      specific CD4(+) and CD8(+) T cells in the infected lungs. Immunohistochemistry
      further revealed higher number of CD8(+) cells in the pulmonary granulomas of
      vaccinated animals. Evaluation of pulmonary immune responses in vaccinated and
      Mtb infected rats by real time PCR at day 15 post-challenge showed reduced
      expression of genes responsible for negative regulation of Th1 immune responses.
      Thus, early protection observed in BCG vaccinated rats correlated with a
      similarly timed shift of immunity towards the Th1 type response. Our data support
      the importance of (i) the Th1-Th2 balance in the control of mycobacterial
      infection and (ii) the value of the Wistar rats in understanding the biology of
      TB.

PMID- 22162758
TI  - Frequency of circulating regulatory T cells increases during chronic HIV
      infection and is largely controlled by highly active antiretroviral therapy.
AB  - Regulatory T cells (Tregs) act by suppressing the activation and effector
      functions of innate and adaptive immune responses. HIV infection impacts Treg
      proportion and phenotype, although discrepant results have been reported
      depending on the patient population and the way Tregs were characterized. The
      effects of highly active antiretroviral therapy (HAART) on Treg frequency have
      not been thoroughly documented. We performed a detailed longitudinal analysis of
      Treg frequency and phenotype in 11 HIV-infected individuals enrolled in a single,
      prospective clinical trial, in which all patients underwent the same treatment
      protocol and were sampled at the same time points. Tregs were characterized for
      their expression of molecules associated with activation, cell cycle, apoptosis,
      or function, and compared to circulating Tregs from a group of age-matched
      healthy individuals.Our results revealed increased proportions, but reduced
      absolute numbers of circulating CD3(+)CD4(+)FOXP3(+) Tregs in chronically
      infected HIV-infected patients. Treg frequency was largely normalized by HAART.
      Importantly, we show that similar conclusions were drawn regardless of the
      combination of markers used to define Tregs. Our results also showed increased
      expression of cell cycle markers (Ki67 and cyclin B) in Tregs from untreated
      infected individuals, which were decreased by HAART. However, the Treg phenotype
      in untreated patients was not consistent with a higher level of generalized
      activation, as they expressed very low levels of CD69, slightly elevated levels
      of HLA-DR and similar levels of GARP compared to Tregs from uninfected donors.
      Moreover, none of these markers was significantly changed by HAART. Treg
      expression of CTLA-4 and cytotoxic molecules was identical between patients and
      controls. The most striking difference in terms of functional molecules was the
      high expression of CD39 by Tregs in untreated patients, which HAART only
      partially controlled.

PMID- 22162759
TI  - Effective antibiotics in combination against extreme drug-resistant Pseudomonas
      aeruginosa with decreased susceptibility to polymyxin B.
AB  - OBJECTIVE: Extreme drug-resistant Pseudomonas aeruginosa (XDR-PA) with decreased
      susceptibility to polymyxin B (PB) has emerged in Singapore, causing infections
      in immunocompromised hosts. Combination therapy may be the only viable
      therapeutic option until new antibiotics become available. The objective of this
      study is to assess the in vitro activity of various antibiotics against local XDR
      PA isolates. METHODS: PA isolates from all public hospitals in Singapore were
      systematically collected between 2006 and 2007. MICs were determined according to
      CLSI guidelines. All XDR-PA isolates identified were genotyped using a PCR-based
      method. Time-kill studies (TKS) were performed with approximately 10(5) CFU/ml at
      baseline using clinically achievable unbound concentrations of amikacin (A),
      levofloxacin (L), meropenem (M), rifampicin (R) and PB alone and in combination.
      Bactericidal activity (primary endpoint) was defined as a >=3 log(10) CFU/ml
      decrease in the colony count from the initial inoculum at 24 hours. RESULTS: 22
      clinical XDR-PA isolates with PB MIC 2-16 ug/ml were collected. From clonal
      typing, 5 clonal groups were identified and nine isolates exhibited clonal
      diversity. In TKS, meropenem plus PB, amikacin plus meropenem, amikacin plus
      rifampicin, amikacin plus PB exhibited bactericidal activity in 8/22, 3/22, 1/22
      and 6/22 isolates at 24 hours respectively. Against the remaining ten isolates
      where none of the dual-drug combination achieved bactericidal activity against,
      only the triple-antibiotic combinations of ARP and AMP achieved bactericidal
      activity against 7/10 and 6/10 isolates respectively. CONCLUSION: Bactericidal
      activity with sustained killing effect of >=99.9% is critical for eradicating XDR
      PA infections, especially in immunocompromised hosts. These findings underscore
      the difficulty of developing combination therapeutic options against XDR-PA,
      demonstrating that at least 3 antibiotics are required in combination and that
      efficacy is strain dependant.

PMID- 22162760
TI  - Saliency changes appearance.
AB  - Numerous studies have suggested that the deployment of attention is linked to
      saliency. In contrast, very little is known about how salient objects are
      perceived. To probe the perception of salient elements, observers compared two
      horizontally aligned stimuli in an array of eight elements. One of them was
      salient because of its orientation or direction of motion. We observed that the
      perceived luminance contrast or color saturation of the salient element
      increased: the salient stimulus looked even more salient. We explored the
      possibility that changes in appearance were caused by attention. We chose an
      event-related potential indexing attentional selection, the N2pc, to answer this
      question. The absence of an N2pc to the salient object provides preliminary
      evidence against involuntary attentional capture by the salient element. We
      suggest that signals from a master saliency map flow back into individual feature
      maps. These signals boost the perceived feature contrast of salient objects, even
      on perceptual dimensions different from the one that initially defined saliency.

PMID- 22162761
TI  - C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent
      activation of transcription factor ZEB in human renal tubular cells.
AB  - BACKGROUND: Replacement of proinsulin C-peptide in type 1 diabetes ameliorates
      nerve and kidney dysfunction, conditions which are associated with a decrease in
      Na,K-ATPase activity. We determined the molecular mechanism by which long term
      exposure to C-peptide stimulates Na,K-ATPase expression and activity in primary
      human renal tubular cells (HRTC) in control and hyperglycemic conditions.
      METHODOLOGY/PRINCIPAL FINDINGS: HRTC were cultured from the outer cortex obtained
      from patients undergoing elective nephrectomy. Ouabain-sensitive rubidium
      ((86)Rb(+)) uptake and Na,K-ATPase activity were determined. Abundance of Na,K
      ATPase was determined by Western blotting in intact cells or isolated basolateral
      membranes (BLM). DNA binding activity was determined by electrical mobility shift
      assay (EMSA). Culturing of HRTCs for 5 days with 1 nM, but not 10 nM of human C
      peptide leads to increase in Na,K-ATPase alpha(1)-subunit protein expression,
      accompanied with increase in (86)Rb(+) uptake, both in normal- and hyperglycemic
      conditions. Na,K-ATPase alpha(1)-subunit expression and Na,K-ATPase activity were
      reduced in BLM isolated from cells cultured in presence of high glucose. Exposure
      to1 nM, but not 10 nM of C-peptide increased PKCepsilon phosphorylation as well
      as phosphorylation and abundance of nuclear ERK1/2 regardless of glucose
      concentration. Exposure to 1 nM of C-peptide increased DNA binding activity of
      transcription factor ZEB (AREB6), concomitant with Na,K-ATPase alpha(1)-subunit
      mRNA expression. Effects of 1 nM C-peptide on Na,K-ATPase alpha(1)-subunit
      expression and/or ZEB DNA binding activity in HRTC were abolished by incubation
      with PKC or MEK1/2 inhibitors and ZEB siRNA silencing. CONCLUSIONS/SIGNIFICANCE:
      Despite activation of ERK1/2 and PKC by hyperglycemia, a distinct pool of PKCs
      and ERK1/2 is involved in regulation of Na,K-ATPase expression and activity by C
      peptide. Most likely C-peptide stimulates sodium pump expression via activation
      of ZEB, a transcription factor that has not been previously implicated in C
      peptide-mediated signaling. Importantly, only physiological concentrations of C
      peptide elicit this effect.

PMID- 22162762
TI  - PTEN modulates miR-21 processing via RNA-regulatory protein RNH1.
AB  - Aberrant miR-21 expression is closely associated with cell proliferation, anti
      apoptosis, migration, invasion, and metastasis in various cancers. However, the
      regulatory mechanism of miR-21 biogenesis is largely unknown. Here, we
      demonstrated that the tumor suppressor PTEN negatively regulates the expression
      of oncogenic miR-21 at the post-transcriptional level. Moreover, our results
      suggest that PTEN plays such a role through the indirect interaction with the
      Drosha complex. To elucidate how PTEN regulates pri- to pre-miR-21 processing, we
      attempted to find PTEN-interacting proteins and identified an RNA-regulatory
      protein, RNH1. Using the sensor to monitor pri-miR-21 processing, we demonstrated
      that RNH1 is necessary and sufficient for pri-miR-21 processing. Moreover, our
      results propose that the nuclear localization of RNH1 is important for this
      function. Further analysis showed that RNH1 directly interacts with the Drosha
      complex and that PTEN blocks this interaction. Taken together, these results
      suggest that the PTEN-mediated miR-21 regulation is achieved by inhibiting the
      interaction between the Drosha complex and RNH1, revealing previously
      unidentified role of PTEN in the oncogenic miR-21 biogenesis.

PMID- 22162763
TI  - A novel multiplex cell viability assay for high-throughput RNAi screening.
AB  - Cell-based high-throughput RNAi screening has become a powerful research tool in
      addressing a variety of biological questions. In RNAi screening, one of the most
      commonly applied assay system is measuring the fitness of cells that is usually
      quantified using fluorescence, luminescence and absorption-based readouts. These
      methods, typically implemented and scaled to large-scale screening format,
      however often only yield limited information on the cell fitness phenotype due to
      evaluation of a single and indirect physiological indicator. To address this
      problem, we have established a cell fitness multiplexing assay which combines a
      biochemical approach and two fluorescence-based assaying methods. We applied this
      assay in a large-scale RNAi screening experiment with siRNA pools targeting the
      human kinome in different modified HEK293 cell lines. Subsequent analysis of
      ranked fitness phenotypes assessed by the different assaying methods revealed
      average phenotype intersections of 50.7+/-2.3%-58.7+/-14.4% when two indicators
      were combined and 40-48% when a third indicator was taken into account. From
      these observations we conclude that combination of multiple fitness measures may
      decrease false-positive rates and increases confidence for hit selection. Our
      robust experimental and analytical method improves the classical approach in
      terms of time, data comprehensiveness and cost.

PMID- 22162764
TI  - Nigeria Anopheles vector database: an overview of 100 years' research.
AB  - Anopheles mosquitoes are important vectors of malaria and lymphatic filariasis
      (LF), which are major public health diseases in Nigeria. Malaria is caused by
      infection with a protozoan parasite of the genus Plasmodium and LF by the
      parasitic worm Wuchereria bancrofti. Updating our knowledge of the Anopheles
      species is vital in planning and implementing evidence based vector control
      programs. To present a comprehensive report on the spatial distribution and
      composition of these vectors, all published data available were collated into a
      database. Details recorded for each source were the locality, latitude/longitude,
      time/period of study, species, abundance, sampling/collection methods,
      morphological and molecular species identification methods, insecticide
      resistance status, including evidence of the kdr allele, and P. falciparum
      sporozoite rate and W. bancrofti microfilaria prevalence. This collation resulted
      in a total of 110 publications, encompassing 484,747 Anopheles mosquitoes in 632
      spatially unique descriptions at 142 georeferenced locations being identified
      across Nigeria from 1900 to 2010. Overall, the highest number of vector species
      reported included An. gambiae complex (65.2%), An. funestus complex (17.3%), An.
      gambiae s.s. (6.5%). An. arabiensis (5.0%) and An. funestus s.s. (2.5%), with the
      molecular forms An. gambiae M and S identified at 120 locations. A variety of
      sampling/collection and species identification methods were used with an increase
      in molecular techniques in recent decades. Insecticide resistance to pyrethroids
      and organochlorines was found in the main Anopheles species across 45 locations.
      Presence of P. falciparum and W. bancrofti varied between species with the
      highest sporozoite rates found in An. gambiae s.s, An. funestus s.s. and An.
      moucheti, and the highest microfilaria prevalence in An. gambiae s.l., An.
      arabiensis, and An. gambiae s.s. This comprehensive geo-referenced database
      provides an essential baseline on Anopheles vectors and will be an important
      resource for malaria and LF vector control programmes in Nigeria.

PMID- 22162765
TI  - SNP/RD typing of Mycobacterium tuberculosis Beijing strains reveals local and
      worldwide disseminated clonal complexes.
AB  - The Beijing strain is one of the most successful genotypes of Mycobacterium
      tuberculosis worldwide and appears to be highly homogenous according to existing
      genotyping methods. To type Beijing strains reliably we developed a robust typing
      scheme using single nucleotide polymorphisms (SNPs) and regions of difference
      (RDs) derived from whole-genome sequencing data of eight Beijing strains. SNP/RD
      typing of 259 M. tuberculosis isolates originating from 45 countries worldwide
      discriminated 27 clonal complexes within the Beijing genotype family. A total of
      16 Beijing clonal complexes contained more than one isolate of known origin, of
      which two clonal complexes were strongly associated with South African origin.
      The remaining 14 clonal complexes encompassed isolates from different countries.
      Even highly resolved clonal complexes comprised isolates from distinct
      geographical sites. Our results suggest that Beijing strains spread globally on
      multiple occasions and that the tuberculosis epidemic caused by the Beijing
      genotype is at least partially driven by modern migration patterns. The SNPs and
      RDs presented in this study will facilitate future molecular epidemiological and
      phylogenetic studies on Beijing strains.

PMID- 22162766
TI  - Characterization of Abcc4 gene amplification in stepwise-selected mouse J774
      macrophages resistant to the topoisomerase II inhibitor ciprofloxacin.
AB  - Exposure of J774 mouse macrophages to stepwise increasing concentrations of
      ciprofloxacin, an antibiotic inhibiting bacterial topoisomerases, selects for
      resistant cells that overexpress the efflux transporter Abcc4 (Marquez et al.
      [2009] Antimicrob. Agents Chemother. 53: 2410-2416), encoded by the Abcc4 gene
      located on Chromosome 14qE4. In this study, we report the genomic alterations
      occurring along the selection process. Abcc4 expression progressively increased
      upon selection rounds, with exponential changes observed between cells exposed to
      150 and 200 uM of ciprofloxacin, accompanied by a commensurate decrease in
      ciprofloxacin accumulation. Molecular cytogenetics experiments showed that this
      overexpression is linked to Abcc4 gene overrepresentation, grading from a partial
      trisomy of Chr 14 at the first step of selection (cells exposed to 100 uM
      ciprofloxacin), to low-level amplifications (around three copies) of Abcc4 locus
      on 1 or 2 Chr 14 (cells exposed to 150 uM ciprofloxacin), followed by high-level
      amplification of Abcc4 as homogeneous staining region (hsr), inserted on 3
      different derivative Chromosomes (cells exposed to 200 uM ciprofloxacin). In
      revertant cells obtained after more than 60 passages of culture without drug, the
      Abcc4 hsr amplification was lost in approx. 70% of the population. These data
      suggest that exposing cells to sufficient concentrations of an antibiotic with
      low affinity for eukaryotic topoisomerases can cause major genomic alterations
      that may lead to the overexpression of the transporter responsible for its
      efflux. Gene amplification appears therefore as a mechanism of resistance that
      can be triggered by non-anticancer agents but contribute to cross-resistance, and
      is partially and slowly reversible.

PMID- 22162767
TI  - Local ischemia and increased expression of vascular endothelial growth factor
      following ocular dissemination of Mycobacterium tuberculosis.
AB  - The pathogenesis of intraocular tuberculosis remains poorly understood partly due
      to the lack of adequate animal models that accurately simulate human disease.
      Using a recently developed model of ocular tuberculosis following aerosol
      infection of guinea pigs with Mycobacterium tuberculosis, we studied the
      microbiological, histological, and clinical features of intraocular tuberculosis
      infection. Viable tubercle bacilli were cultivated from all eyes by Day 56 after
      aerosol delivery of ~200 bacilli to guinea pig lungs. Choroidal tuberculous
      granulomas showed reduced oxygen tension, as evidenced by staining with the
      hypoxia-specific probe pimonidazole, and expression of vascular endothelial
      growth factor (VEGF) was detected in the retinal pigment epithelium (RPE) and
      photoreceptors. Fundoscopic examination of M. tuberculosis-infected guinea pig
      eyes revealed altered vascular architecture and chorioretinal hemorrhage by Day
      56 after infection. This model may be useful in further elucidating the
      pathogenesis of ocular tuberculosis, as well as in developing tools for diagnosis
      and assessment of antituberculosis treatment responses in the eye.

PMID- 22162768
TI  - Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes
      differentially impact on electrophysiological correlates of error processing.
AB  - Recent studies as well as theoretical models of error processing assign
      fundamental importance to the brain's dopaminergic system. Research about how the
      electrophysiological correlates of error processing--the error-related negativity
      (ERN) and the error positivity (Pe)--are influenced by variations of common
      dopaminergic genes, however, is still relatively scarce. In the present study, we
      therefore investigated whether polymorphisms in the DAT1 gene and in the DRD4
      gene, respectively, lead to interindividual differences in these error processing
      correlates. One hundred sixty participants completed a version of the Eriksen
      Flanker Task while a 26-channel EEG was recorded. The task was slightly modified
      in order to increase error rates. During data analysis, participants were split
      into two groups depending on their DAT1 and their DRD4 genotypes, respectively.
      ERN and Pe amplitudes after correct responses and after errors as well as
      difference amplitudes between errors and correct responses were analyzed. We
      found a differential effect of DAT1 genotype on the Pe difference amplitude but
      not on the ERN difference amplitude, while the reverse was true for DRD4
      genotype. These findings are in line with predictions from theoretical models of
      dopaminergic transmission in the brain. They furthermore tie results from
      clinical investigations of disorders impacting on the dopamine system to genetic
      variations known to be at-risk genotypes.

PMID- 22162769
TI  - Nascentome analysis uncovers futile protein synthesis in Escherichia coli.
AB  - Although co-translational biological processes attract much attention, no general
      and easy method has been available to detect cellular nascent polypeptide chains,
      which we propose to call collectively a "nascentome." We developed a method to
      selectively detect polypeptide portions of cellular polypeptidyl-tRNAs and used
      it to study the generality of the quality control reactions that rescue dead-end
      translation complexes. To detect nascent polypeptides, having their growing ends
      covalently attached to a tRNA, cellular extracts are separated by SDS-PAGE in two
      dimensions, first with the peptidyl-tRNA ester bonds preserved and subsequently
      after their in-gel cleavage. Pulse-labeled nascent polypeptides of Escherichia
      coli form a characteristic line below the main diagonal line, because each of
      them had contained a tRNA of nearly uniform size in the first-dimension
      electrophoresis but not in the second-dimension. The detection of nascent
      polypeptides, separately from any translation-completed polypeptides or
      degradation products thereof, allows us to follow their fates to gain deeper
      insights into protein biogenesis and quality control pathways. It was revealed
      that polypeptidyl-tRNAs were significantly stabilized in E. coli upon dysfunction
      of the tmRNA-ArfA ribosome-rescuing system, whose function had only been studied
      previously using model constructs. Our results suggest that E. coli cells are
      intrinsically producing aberrant translation products, which are normally
      eliminated by the ribosome-rescuing mechanisms.

PMID- 22162770
TI  - A tissue-specific approach to the analysis of metabolic changes in Caenorhabditis
      elegans.
AB  - The majority of metabolic principles are evolutionarily conserved from nematodes
      to humans. Caenorhabditis elegans has widely accelerated the discovery of new
      genes important to maintain organismic metabolic homeostasis. Various methods
      exist to assess the metabolic state in worms, yet they often require large animal
      numbers and tend to be performed as bulk analyses of whole worm homogenates,
      thereby largely precluding a detailed studies of metabolic changes in specific
      worm tissues. Here, we have adapted well-established histochemical methods for
      the use on C. elegans fresh frozen sections and demonstrate their validity for
      analyses of morphological and metabolic changes on tissue level in wild type and
      various mutant strains. We show how the worm presents on hematoxylin and eosin
      (H&E) stained sections and demonstrate their usefulness in monitoring and the
      identification of morphological abnormalities. In addition, we demonstrate how
      Oil-Red-O staining on frozen worm cross-sections permits quantification of lipid
      storage, avoiding the artifact-prone fixation and permeabilization procedures of
      traditional whole-mount protocols. We also adjusted standard enzymatic stains for
      respiratory chain subunits (NADH, SDH, and COX) to monitor metabolic states of
      various C. elegans tissues. In summary, the protocols presented here provide
      technical guidance to obtain robust, reproducible and quantifiable tissue
      specific data on worm morphology as well as carbohydrate, lipid and mitochondrial
      energy metabolism that cannot be obtained through traditional biochemical bulk
      analyses of worm homogenates. Furthermore, analysis of worm cross-sections
      overcomes the common problem with quantification in three-dimensional whole-mount
      specimens.

PMID- 22162771
TI  - Structural studies of beta-carbonic anhydrase from the green alga Coccomyxa:
      inhibitor complexes with anions and acetazolamide.
AB  - The beta-class carbonic anhydrases (beta-CAs) are widely distributed among lower
      eukaryotes, prokaryotes, archaea, and plants. Like all CAs, the beta-enzymes
      catalyze an important physiological reaction, namely the interconversion between
      carbon dioxide and bicarbonate. In plants the enzyme plays an important role in
      carbon fixation and metabolism. To further explore the structure-function
      relationship of beta-CA, we have determined the crystal structures of the
      photoautotroph unicellular green alga Coccomyxa beta-CA in complex with five
      different inhibitors: acetazolamide, thiocyanate, azide, iodide, and phosphate
      ions. The tetrameric Coccomyxa beta-CA structure is similar to other beta-CAs but
      it has a 15 amino acid extension in the C-terminal end, which stabilizes the
      tetramer by strengthening the interface. Four of the five inhibitors bind in a
      manner similar to what is found in complexes with alpha-type CAs. Iodide ions,
      however, make contact to the zinc ion via a zinc-bound water molecule or
      hydroxide ion--a type of binding mode not previously observed in any CA. Binding
      of inhibitors to Coccomyxa beta-CA is mediated by side-chain movements of the
      conserved residue Tyr-88, extending the width of the active site cavity with 1.5
      1.8 A. Structural analysis and comparisons with other alpha- and beta-class
      members suggest a catalytic mechanism in which the movements of Tyr-88 are
      important for the CO(2)-HCO(3)(-) interconversion, whereas a structurally
      conserved water molecule that bridges residues Tyr-88 and Gln-38, seems important
      for proton transfer, linking water molecules from the zinc-bound water to His-92
      and buffer molecules.

PMID- 22162772
TI  - Evolution of sexual dimorphism in the digit ratio 2D:4D--relationships with body
      size and microhabitat use in iguanian lizards.
AB  - The ratio between lengths of digit II and IV (digit ratio 2D:4D) is a
      morphological feature that likely affects tetrapod locomotor performances in
      different microhabitats. Modifications of this trait may be triggered by changes
      in steroids concentrations during embryo development, which might reflect direct
      selection acting on digit ratio or be solely a consequence of hormonal
      differences related for example to body size. Here we apply both conventional and
      phylogenetic analyses on morphological data from 25 lizard species of 3 families
      of Iguania (Iguanidae, Polychrotidae, and Tropiduridae), in order to verify
      whether selective pressures related to locomotion in different microhabitats
      could override the prenatal developmental cues imposed on the digit ratio 2D:4D
      by differences in body size between males and females. Data suggest that this
      trait evolved in association with ecological divergence in the species studied,
      despite the clear effect of body size on the digit ratio 2D:4D. The ecological
      associations of size-corrected digit ratios were restricted to one sex, and
      females of species that often use perches exhibited small digit ratios in the
      front limbs, which translated into larger sexual dimorphism indexes of arboreal
      species. The results, together with the subsequent discussion, provide outlines
      for further investigation about possible developmental mechanisms related to the
      evolution of adaptive changes in digit lengths that may have occurred during the
      evolution of ecological divergence in squamates.

PMID- 22162773
TI  - Small interfering RNA against transcription factor STAT6 leads to increased
      cholesterol synthesis in lung cancer cell lines.
AB  - STAT6 transcription factor has become a potential molecule for therapeutic
      intervention because it regulates broad range of cellular processes in a large
      variety of cell types. Although some target genes and interacting partners of
      STAT6 have been identified, its exact mechanism of action needs to be elucidated.
      In this study, we sought to further characterize the molecular interactions,
      networks, and functions of STAT6 by profiling the mRNA expression of STAT6
      silenced human lung cells (NCI-H460) using microarrays. Our analysis revealed 273
      differentially expressed genes after STAT6 silencing. Analysis of the gene
      expression data with Ingenuity Pathway Analysis (IPA) software revealed Gene
      expression, Cell death, Lipid metabolism as the functions associated with highest
      rated network. Cholesterol biosynthesis was among the most enriched pathways in
      IPA as well as in PANTHER analysis. These results have been validated by real
      time PCR and cholesterol assay using scrambled siRNA as a negative control.
      Similar findings were also observed with human type II pulmonary alveolar
      epithelial cells, A549. In the present study we have, for the first time, shown
      the inverse relationship of STAT6 with the cholesterol biosynthesis in lung
      cancer cells. The present findings are potentially significant to advance the
      understanding and design of therapeutics for the pathological conditions where
      both STAT6 and cholesterol biosynthesis are implicated viz. asthma,
      atherosclerosis etc.

PMID- 22162774
TI  - Analysis of transcriptome differences between resistant and susceptible strains
      of the citrus red mite Panonychus citri (Acari: Tetranychidae).
AB  - BACKGROUND: The citrus red mite is a worldwide citrus pest and a common
      sensitizing allergen of asthma and rhinitis. It has developed strong resistance
      to many registered acaricides, However, the molecular mechanisms of resistance
      remain unknown. we therefore used next generation sequencing technology to
      investigate the global transcriptomes between resistant strains and susceptible
      strains. RESULTS: We obtained 34,159, 30,466 and 32,217 unigenes by assembling
      the SS reads, RS reads and SS&RS reads respectively. There are total 17,581
      annotated unigenes from SS&RS reads by BLAST searching databases of nr, the
      Clusters of Orthologous Groups (COGs) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) with an E-value <= 1e-5, in which 7,075 unigenes were annotated in the COG
      database, 12, 712 unigenes were found in the KEGG database and 3,812 unigenes
      were assigned to Gene ontology (GO). Moreover, 2,701 unigenes were judged to be
      the differentially expressed genes (DEGs) based on the uniquely mapped reads.
      There are 219 pathways in all annotated unigenes and 198 pathways in DEGs that
      mapped to the KEGG database. We identified 211 metabolism genes and target genes
      related to general insecticide resistance such as P450 and Cytochrome b, and
      further compared their differences between RS and SS. Meanwhile, we identified
      105 and 194 genes related to growth and reproduction, respectively, based on the
      mode of action of Hexythiazox. After further analyses, we found variation in
      sequences but not in gene expression related to mite growth and reproduction
      between different strains. CONCLUSION: To our knowledge, this is the first
      comparative transcriptome study to discover candidate genes involved in
      phytophagous mite resistance. This study identified differential unigenes related
      to general pesticide resistance and organism growth and reproduction in P. citri.
      The assembled, annotated transcriptomes provide a valuable genomic resource for
      further understanding the molecular basis of resistance mechanisms.

PMID- 22162775
TI  - Regulation of virulence gene expression resulting from Streptococcus pneumoniae
      and nontypeable Haemophilus influenzae interactions in chronic disease.
AB  - Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal
      cavity mediated, in part, by polymicrobial communities of bacteria. Recent
      molecular studies have confirmed the importance of Streptococcus pneumoniae and
      nontypeable Haemophilus influenzae (NTHi) in CRS. Here, we hypothesize that
      interaction between S. pneumoniae and NTHi mixed-species communities cause a
      change in bacterial virulence gene expression. We examined CRS as a model human
      disease to validate these polymicrobial interactions. Clinical strains of S.
      pneumoniae and NTHi were grown in mono- and co-culture in a standard biofilm
      assay. Reverse transcriptase real-time PCR (RTqPCR) was used to measure gene
      expression of key virulence factors. To validate these results, we investigated
      the presence of the bacterial RNA transcripts in excised human tissue from
      patients with CRS. Consequences of physical or chemical interactions between
      microbes were also investigated. Transcription of NTHi type IV pili was only
      expressed in co-culture in vitro, and expression could be detected ex vivo in
      diseased tissue. S. pneumoniae pyruvate oxidase was up-regulated in co-culture,
      while pneumolysin and pneumococcal adherence factor A were down-regulated. These
      results were confirmed in excised human CRS tissue. Gene expression was
      differentially regulated by physical contact and secreted factors. Overall, these
      data suggest that interactions between H. influenzae and S. pneumoniae involve
      physical and chemical mechanisms that influence virulence gene expression of
      mixed-species biofilm communities present in chronically diseased human tissue.
      These results extend previous studies of population-level virulence and provide
      novel insight into the importance of S. pneumoniae and NTHi in CRS.

PMID- 22162776
TI  - Gene transfer using micellar nanovectors inhibits choroidal neovascularization in
      vivo.
AB  - PURPOSE: Age-related macular degeneration caused by choroidal neovascularization
      (CNV) remains difficult to be treated despite the recent advent of several
      treatment options. In this study, we investigated the in vivo angiogenic control
      by intravenous injection of polyion complex (PIC) micelle encapsulating plasmid
      DNA (pDNA) using a mice CNV model. METHODS: The transfection efficiency of the
      PIC micelle was investigated using the laser-induced CNV in eight-week-old male
      C57 BJ/6 mice. Firstly, each mouse received intravenous injection of micelle
      encapsulating pDNA of Yellow Fluorescent Protein (pYFP) on days 1,3 and 5. The
      expression of YFP was analyzed using fluorescein microscopy and western blotting
      analysis. In the next experiments, each mouse received intravenous injection of
      micelle encapsulating pDNA of soluble Fms-like tyrosine kinase-1 (psFlt-1) 1,3
      and 5 days after the induction of CNV and the CNV lesion was analyzed by
      choroidal flatmounts on day 7. RESULTS: Fluorescein microscopy and western
      blotting analysis revealed that the expression of YFP was confirmed in the CNV
      area after injection of the PIC micelle, but the expression was not detected
      neither in mice that received naked pDNA nor those without CNV. Furthermore, the
      CNV area in the mice that received intravenous injection of the psFlt-1
      encapsulated PIC micelle was significantly reduced by 65% compared to that in
      control mice (p<0.01). CONCLUSIONS: Transfection of sFlt-1 with the PIC micelle
      by intravenous injection to mice CNV models showed significant inhibition of CNV.
      The current results revealed the significant potential of nonviral gene therapy
      for regulation of CNV using the PIC micelle encapsulating pDNA.

PMID- 22162777
TI  - The Gln32Lys polymorphism in HSP22 of Zhikong scallop Chlamys farreri is
      associated with heat tolerance.
AB  - BACKGROUND: Heat shock protein 22 is a member of small heat shock proteins with
      molecular chaperone activity. Though their multiple functions have been well
      characterized, there is no report about the association between the polymorphisms
      of HSP22 and heat tolerance. METHODOLOGY: Three single nucleotide polymorphisms
      were identified in HSP22 from scallop Chlamys farreri (CfHSP22), and the +94 C-A
      locus was found to be nonsynonymous. Three genotypes at locus +94, A/A, A/C and
      C/C, were revealed by using Bi-PASA PCR analysis, and their frequencies were
      19.5%, 27.6% and 52.9% in the heat resistant stock, while 9.3%, 17.4% and 73.3%
      in the heat susceptible stock, respectively. The frequency differences of the
      three genotypes were significant (P<0.05) between the two stocks. After
      incubating at 30 degrees C for 84 h, the cumulative mortality of scallops with
      +94 C/C genotype and +94 A/C genotypes was 95% and 90%, respectively, which was
      significantly higher (P<0.01) than that of scallops with +94 A/A genotype (70%).
      The molecular chaperone activity of two His-tagged fusion proteins, rCfHSP22Q
      with +94 C/C genotype and rCfHSP22K with +94 A/A genotype were analyzed by
      testing the ability of protecting citrate synthase (CS) against thermal
      inactivation in vitro. After incubated with rCfHSP22Q or rCfHSP22K at 38 degrees
      C for 1 h, the activity of CS lost 50% and 45%, and then recovered to 89% and 95%
      of the original activity following 1 h restoration at 22 degrees C, respectively,
      indicating that the mutation from Gln to Lys at this site might have an impact on
      molecular chaperone activities of CfHSP22. CONCLUSIONS: These results implied
      that the polymorphism at locus +94 of CfHSP22 was associated with heat tolerance
      of scallop, and the +94 A/A genotype could be a potential marker available in
      future selection of Zhikong scallop with heat tolerance.

PMID- 22162778
TI  - Substrate adhesion regulates sealing zone architecture and dynamics in cultured
      osteoclasts.
AB  - The bone-degrading activity of osteoclasts depends on the formation of a
      cytoskeletal-adhesive super-structure known as the sealing zone (SZ). The SZ is a
      dynamic structure, consisting of a condensed array of podosomes, the elementary
      adhesion-mediating structures of osteoclasts, interconnected by F-actin
      filaments. The molecular composition and structure of the SZ were extensively
      investigated, yet despite its major importance for bone formation and
      remodelling, the mechanisms underlying its assembly and dynamics are still poorly
      understood. Here we determine the relations between matrix adhesiveness and the
      formation, stability and expansion of the SZ. By growing differentiated
      osteoclasts on micro-patterned glass substrates, where adhesive areas are
      separated by non-adhesive PLL-g-PEG barriers, we show that SZ growth and fusion
      strictly depend on the continuity of substrate adhesiveness, at the micrometer
      scale. We present a possible model for the role of mechanical forces in SZ
      formation and reorganization, inspired by the current data.

PMID- 22162779
TI  - Vision-related quality of life and self-rated satisfaction outcomes of
      rhegmatogenous retinal detachment surgery: three-year prospective study.
AB  - BACKGROUND: Subjective functional outcomes measurements, such as vision health
      related quality of life (VRQoL) and self-rated satisfaction measures can provide
      helpful multidimensional vision health information that is more comprehensive
      than traditional objective measures, such as best corrected visual acuity (BCVA).
      The purpose of this study is to demonstrate 3-year longitudinal postoperative
      VRQoL and self-rated satisfaction changes after rhegmatogenous retinal detachment
      (RRD) surgery. METHODOLOGY/PRINCIPAL FINDINGS: A prospective case series report
      was conducted in 92 RRD patients who underwent surgery during January 2004
      through December 2006. Preoperative, 3-month, 1-year and 3-year postoperative
      patient VRQoL and self-rated satisfaction were assessed by face-to-face
      interviews. The importance of objective variables for predicting three dependent
      variables: CLVQOL composite scores change, 3-year postoperative CVLQOL composite
      score and self-rated satisfaction degree scores were calculated by stepwise
      multivariate linear or logistic regression analysis methods. RESULTS: The total
      CLVQOL composite scores change ranged between -48 and 90 (mean+/-standard
      deviation: 19.48+/-31.34), including positive changes in 62 patients. The self
      rated satisfaction degree scores ultimately improved in 86 patients as compared
      with preoperative degrees. Statistically significant increases occurred only in
      the composite scores of subscale mobility and self-rated satisfaction degrees in
      the first 3 months, while the composite scores of the remaining subscales, and
      the total CLVQOL, BCVA in the RRD eye and weighted average BCVA, increased
      steadily throughout the first postoperative year. A better 3-year postoperative
      weighted average BCVA was associated with all of the 3 dependent outcome
      variables. CONCLUSIONS: VRQoL of RRD patients improved substantially after
      surgery and they were satisfied with their postoperative vision. The BCVA, VRQoL
      and self-rated satisfactory degree scores recovered in different patterns, and
      supplemented each other in the RRD surgery outcomes evaluated. Surgeons are
      advised to pay closer attention to binocular vision in RRD patients, and make
      efforts to explain the results of surgery.

PMID- 22162780
TI  - Interactions between synchrotron radiation X-ray and biological tissues -
      theoretical and clinical significance.
AB  - Synchrotron radiation (SR) X-ray has great potential for its applications in both
      diagnosis and treatment of diseases, due to its characteristic properties
      including coherence, collimation, monochromaticity, and exceptional brightness.
      Great advances have been made regarding potential medical applications of SR X
      ray in recent years, particularly with the development of the third generation of
      SR light sources. However, multiple studies have also suggested damaging effects
      of SR X-ray on biological samples ranging from protein crystals to cells and
      biological tissues. It has become increasingly important to conduct comprehensive
      studies on two closely related topics regarding SR X-ray in medical applications:
      The safety issues regarding the medical applications of SR X-ray and the
      fundamental mechanisms underlying the interactions between SR X-ray and
      biological tissues. In this article, we attempted to provide an overview of the
      literatures regarding these two increasingly significant topics. We also proposed
      our hypothesis that there are significant differences between the biological
      tissue-damaging mechanisms of SR X-ray and those of normal X-ray, due to the
      characteristic properties of SR X-ray such as high dose rate. Future studies are
      warranted to test this hypothesis, which may profoundly improve our understanding
      regarding the fundamental mechanisms underlying the interactions between light
      and matter. These studies would also constitute an essential basis for
      establishing the safety standard for the medical applications of SR X-ray.

PMID- 22162781
TI  - An anti-coagulation agent Futhan preferentially targets GABA(A) receptors in
      lungepithelia: implication in treating asthma.
AB  - Futhan is a serine protease inhibitor and medicine in the treatment of
      disseminated intravascular coagulation (DIC) and acute pancreatitis. It is
      metabolized quickly in vivo. Here we show that Futhan reversibly inhibits NMDA
      receptors in hippocampal neurons and GABA(A) receptors both in hippocampal
      neurons and in A549 cells, a human alveolar epithelial cell line. The effect of
      Futhan on GABA(A) receptors in A549 cells is much more potent than its effect on
      GABA(A) receptors in hippocampal neurons (IC(50): 0.9 MUM V.S. 7.3 MUM). Since
      GABA(A) receptors are also expressed in various non-neuronal tissues,
      particularly in airway epithelia and GABA promotes mucus production during
      asthma, our findings indicate that Futhan may be developed as a novel aerosolized
      therapeutic to treat asthma through blocking GABA(A) receptors in the lung.

PMID- 22162782
TI  - Effect of cutaneous blood flow on absorption of insulin: a methodological study
      in healthy male volunteers.
AB  - Absorption of drugs from subcutaneous tissue depends on several factors,
      including tissue perfusion at the administration site. Tissue perfusion can be
      manipulated by e.g. application of local heat. This may subsequently alter the
      rate or amount of absorption of drugs from a subcutaneous depot. The aim of the
      present study was to investigate if increased tissue perfusion after controlled
      local heating can change the absorption of subcutaneously administered short
      acting insulin (Actrapid(r), 100IU/ml). Thirteen healthy Caucasian males
      participated in two randomized experimental sessions; one session with locally
      applied controlled heat at the injection site, and a control session without
      local heat application. Tissue perfusion (blood flow) was monitored with Laser
      Doppler Imaging, and blood samples were taken to assess the levels of glucose and
      insulin. Local heat application at the site of insulin injection significantly
      enhanced tissue perfusion by approximately 145%. However, no correlation was
      found between insulin absorption and tissue perfusion. Based on our findings, it
      was concluded that tissue perfusion is not the rate-limiting factor in the
      absorption of high-concentration short-acting insulin from a subcutaneous depot.
      It is suggested that dissociation of insulin hexamers into dimers and monomers is
      a major rate limiting factor to the absorption.

PMID- 22162783
TI  - Remodeling in vein expresses arterial phenotype in hyperhomocysteinemia.
AB  - Accumulating evidences suggest that homocysteine, a non-protein amino acid, is
      involved in vessel remodeling and blood flow at elevated level, although the
      exact mechanism is unclear. Here we hypothesized that homocysteine affects vein
      in such a way that vein develops arterial phenotype. We tested our hypothesis
      employing wild type (WT, C57BL/6J) and CBS+/- (cystathionine beta-synthase
      heterozygote, a genetic model of hyperhomocysteinemia) supplemented with or
      without folic acid (FA, a homocysteine lowering agent). Vena cava blood flow was
      measured by ultrasound transonic flow probe. Tissue collagen and elastin were
      detected by histochemistry. Super oxide was detected by dihydroethidium (DHE)
      staining. Expressions of MMP-2, -9, -12, TIMP -2,-4, were measured by Western
      blot. MMP-13, TIMP-1, -3, and vein and aortic markers, EphB4 and EphrinB2,
      respectively were measured by RT-PCR. The results indicated relatively low blood
      flow and significant increase of collagen/elastin ratio in the CBS+/- mice
      compared to WT. Although FA treatment did not alter blood flow in CBS+/- mice,
      the collagen/elastin ratio was normalized. A relatively increased content of
      super oxide and gelatinase activity was observed in CBS+/- vena cava vs WT and
      normalized by FA treatment. Western blot analyses showed significant increase in
      MMP-9,-12 and decrease in TIMP-2, -4 expressions. Expressions of MMP-13, TIMP-1
      and -3, Ephrin B2 were increased, whereas EphB4 was decreased with reverse change
      in FA treatment, with no change in MMP-13 and TIMP-1. We conclude that chronic
      HHcy causes vascular remodeling that expresses arterial phenotype in vein.

PMID- 22162784
TI  - Unraveling a masticatory - oculomotor neural pathway in rat: Implications for a
      pathophysiological neural circuit in human?
AB  - Anterograde tracers were injected into the mesencephalic trigeminal nucleus (Vme)
      in pons, labeled axons and terminals were observed in ipsilateral oculomotor
      (III) and trochlear (IV) nuclei, as well as in interstitial nucleus of Cajar and
      Darkschewitsch nucleus (INC/DN), the well-known premotor nuclei to the III/IV,
      but not in abducens nucleus and central mesencephalic and paramedian pontine
      reticular formation (CMRF/PPRF). Retrogradely labeled INC/DN neurons do ensue
      from injection of tracers into the III. Confocal microscopy revealed labeled Vme
      axonal terminals contact with labeled pre-oculomotor neurons in the INC/DN. In
      response to electrical stimulation of trigeminal nerve root (TR) jaw muscle
      branches, which contains peripheral processes of the jaw muscle spindle,
      extracellular unit discharges were recorded in the ipsilateral III/IV and INC/DN.
      Electromyography (EMG) was also recorded from superior rectus (SR) and levator
      palpebrae (LP) following electrical stimulation of the TR. Moreover, stimulation
      of the TR induced Fos expression in the INC/DN pre-oculomotor neurons, but not in
      CMRF/PPRF that harbors horizontal eye moving premotor neurons. By injection of
      retrograde tracers into the III combined with Fos immunostain, double labeled pre
      oculomotor neurons were observed in the INC/DN. About 80% of retrogradely labeled
      III premotor neurons express Fos. These results suggest a neural pathway from the
      masticatory Vme neurons to the oculomotor system that is probably involved
      exclusively in vertical and torsional eye movement as well as eyelid retraction.
      The potential relationship between this pathway and Marcus Gunn Syndrome (MGS), a
      congenital jaw-winking syndrome, was discussed.

PMID- 22162786
TI  - Monoenomycin: A Simplified Trienomycin A Analogue that Manifests Anticancer
      Activity.
AB  - Macrocyclic natural products are a powerful class of lead-like chemical entities.
      Despite commonly violating Lipinski's "rule of 5", these compounds often
      demonstrate superior drug-like physicochemical and pharmacokinetic attributes
      when compared to their acyclic counterparts. However, the elaborate structural
      architectures of such molecules require rigorous synthetic investigation that
      complicates analogue development and their application to drug discovery
      programs. To circumvent these limitations, a conformation-based approach using
      limited SAR and molecular modeling was implemented to design simplified analogues
      of trienomycin A, in which the corresponding analogues could be prepared in a
      succinct manner to rapidly identify essential structural components necessary for
      biological activity. Trienomycin A is a member of the ansamycin family of natural
      products that possesses potent anticancer activity. These studies revealed a
      novel trienomycin A analogue, monoenomycin, which manifests potent anticancer
      activity.

PMID- 22162785
TI  - Modulation of acid-sensing ion channels: molecular mechanisms and therapeutic
      potential.
AB  - Increases in extracellular proton concentrations, which takes place in
      physiological conditions such as synaptic signaling and pathological conditions
      such as tissue inflammation, ischemic stroke, traumatic brain injury, and
      epileptic seizure, activates a unique family of membrane ion channels; the acid
      sensing ion channels (ASICs). All ASICs belong to amiloride-sensitive
      degenerin/epithelial Na(+) channel superfamily. Four genes encoded at seven sub
      units have been identified. ASICs are expressed primarily in neurons and have
      been shown to play critical roles in synaptic plasticity, learning/memory, fear
      conditioning, sensory transduction, pain perception, ischemic brain injury,
      seizure, and other neurological as well as psychological disorders. Although
      protons are the primary activator for ASICs, the properties and/or level of
      expression of these channels are modulated dramatically by neuropeptides, di-and
      polyvalent cations, inflammatory mediators, associated proteins, and protein
      phosphorylations, etc. Modulation of ASICs can result in profound changes in the
      activities and functions of these channels in both physiological and pathological
      processes. In this article, we provide an up to date review on the modulations of
      ASICs by exogenous agents and endogenous signaling molecules. A better
      understanding of how ASICs can be modulated should help define new strategies to
      counteract the deleterious effects of dysregulated ASIC activity.

PMID- 22162787
TI  - Computer assisted navigation in knee arthroplasty.
AB  - Computer assisted surgery (CAS) was used to improve the positioning of implants
      during total knee arthroplasty (TKA). Most studies have reported that computer
      assisted navigation reduced the outliers of alignment and component
      malpositioning. However, additional sophisticated studies are necessary to
      determine if the improvement of alignment will improve long-term clinical results
      and increase the survival rate of the implant. Knowledge of CAS-TKA technology
      and understanding the advantages and limitations of navigation are crucial to the
      successful application of the CAS technique in TKA. In this article, we review
      the components of navigation, classification of the system, surgical method,
      potential error, clinical results, advantages, and disadvantages.

PMID- 22162788
TI  - Total hip arthroplasty using two-incision technique.
AB  - BACKGROUND: To evaluate the effectiveness of minimally invasive surgery total hip
      arthroplasty (THA) using the two-incision technique as described by Mears.
      METHODS: From January 2003 to December 2006, sixty-four patients underwent total
      hip arthroplasty using the one-incision (group I) and two-incision (group II)
      technique by one surgeon. There were 34 hips in group I and 30 hips in group II.
      There was no difference in age, gender, and causes of THA between the two groups.
      We evaluated the operation time, bleeding amount, incision length, ambulation,
      hospital stay, and complications between the two groups. RESULTS: There was no
      difference in the bleeding amount between the two groups. Operation time was
      longer in the two-incision group than in the one-incision group. Operation time
      of the two-incision technique could be reduced after 15 cases. Patients started
      ambulation after surgery earlier in group II than group I, and the hospital stay
      was shorter in group II than in group I. There was no difference in clinical
      results between the two groups. There was no difference in component position of
      the acetabular cup and femoral stem between the two groups. Intraoperative
      periprosthetic fracture occurred in four cases (13.3%) in group II. CONCLUSIONS:
      Two-incision THA has the advantage of rapid recovery and shorter hospital stay.
      However, longer operation time and a high complication rate compared to one
      incision are problems that need to be solved in the two-incision technique.

PMID- 22162789
TI  - The analysis of risk factors in no thumb test in total knee arthroplasty.
AB  - BACKGROUND: We would like to analyze the risk factors of no thumb test among knee
      alignment tests during total knee arthroplasty surgery. METHODS: The 156 cases of
      total knee arthroplasty by an operator from October 2009 to April 2010 were
      analyzed according to preoperative indicators including body weight, height,
      degree of varus deformity, and patella subluxation and surgical indicators such
      as pre-osteotomy patella thickness, degree of patella degeneration, no thumb test
      which was evaluated after medial prepatella incision and before bone resection
      (1st test), no thumb test which was evaluated with corrective valgus stress (2nd
      test, J test), and the kind of prosthesis. We comparatively analyzed indicators
      affecting no thumb test (3rd test). RESULTS: There was no relation between age,
      sex, and body weight and no thumb test (3rd test). Patellar sulcus angle (p =
      0.795), patellar congruence angle (p = 0.276) and preoperative mechanical axis
      showed no relationship. The 1st no thumb test (p = 0.007) and 2nd test (p =
      0.002) showed significant relation with the 3rd no thumb test. Among surgical
      indicators, pre-osteotomy patella thickness (p = 0.275) and degeneration of
      patella (p = 0.320) were not relevant but post-osteotomy patellar thickness (p =
      0.002) was relevant to no thumb test (3rd test). According to prosthesis, there
      was no significance with Nexgen (p = 0.575). However, there was significant
      correlation between Scorpio (p = 0.011), Vanguard (p = 0.049) and no thumb test
      (3rd test). Especially, Scorpio had a tendency to dislocate the patella, but
      Vanguard to stabilize the patella. CONCLUSIONS: No thumb test (3rd test) is
      correlated positively with 1st test, 2nd test, and post-osteotomy patella
      thickness. Therefore, the more patella osteotomy and the prosthesis with high
      affinity to patellofemoral alignment would be required for correct patella
      alignment.

PMID- 22162790
TI  - Medial unicompartmental knee arthroplasty in patients with spontaneous
      osteonecrosis of the knee.
AB  - BACKGROUND: We analyzed the clinical and radiologic results of patients with
      spontaneous osteonecrosis of the knee treated by minimally invasive medial
      unicompartmental arthroplasty using Oxford Uni. METHODS: We reviewed 22 knees in
      21 patients which were treated for spontaneous osteonecrosis between 2002 and
      2006. Patients included one male and 20 females. The mean age was 70.8 years
      (range, 53 to 82 years). The mean follow-up period was 70.3 months (range, 48 to
      93 months). The clinical results were evaluated using the Hospital for Special
      Surgery (HSS) knee score and the range of motion of the knee preoperatively and
      at the final follow-up. Preoperative plain radiographs and magnetic resonance
      images were analyzed to determine the size and stage of osteonecrotic lesions.
      RESULTS: The mean HSS knee score was 64.3 (range, 54 to 75) preoperatively and
      92.0 (range, 71 to 100) at the final follow-up. The mean preoperative flexion
      contracture was 8.9 degrees  (range, 0 to 15 degrees ) and 0.2 degrees  (range, 0
      to 5 degrees ) at the final follow-up. The mean further flexion increased from
      138.6 degrees  (range, 100 to 145 degrees ) preoperatively to 145.6 degrees 
      (range, 140 to 150 degrees ) at the final follow-up. Active full flexion was
      possible within 2 months of the operation. The squatting position was possible in
      16 patients (84.2%) out of 19, except one case of bronchiectasis and one case of
      spine fracture. The cross-leg posture was possible in 19 patients (90.5%) out of
      21. The mean tibiofemoral angle was improved from varus 0.98 degrees  to valgus
      3.22 degrees . Meniscal bearing dislocation occurred in 2 cases and femoral
      component loosening occurred in 1 case. CONCLUSIONS: Unicompartmental knee
      arthroplasty using Oxford Uni could be an alternative treatment option in
      spontaneous osteonecrosis of the knee.

PMID- 22162791
TI  - Clinical results of technique for double bundle anterior cruciate ligament
      reconstruction using hybrid femoral fixation and Retroscrew.
AB  - BACKGROUND: Anatomic anterior cruciate ligament (ACL) reconstruction has been
      presented as a means to more accurately restore the native anatomy of this
      ligament. This article describes a new method that uses a double bundle to
      perform ACL reconstruction and to evaluate the clinical outcome. METHODS: Grafts
      are tibialis anterior tendon allograft for anteromedial bundle (AMB) and
      hamstring tendon autograft without detachment of the tibial insertion for
      posterolateral bundle (PLB). This technique creates 2 tunnels in both the femur
      and tibia. Femoral fixation was done by hybrid fixation using Endobutton and
      Rigidfix for AMB and by biointerference screw for PLB. Tibial fixations are done
      by Retroscrew for AMB and by native insertion of hamstring tendon for PLB. Both
      bundles are independently and differently tensioned. We performed ACL
      reconstruction in 63 patients using our new technique. Among them, 47
      participated in this study. The patients were followed up with clinical
      examination, Lysholm scales and International Knee Documentation Committee (IKDC)
      scoring system and radiological examination with a minimum 12 month follow-up
      duration. RESULTS: Significant improvement was seen on Lachman test and pivot
      shift test between preoperative and last follow-up. Only one of participants had
      flexion contracture about 5 degrees at last follow-up. In anterior drawer test by
      KT-1000, authors found improvement from average 8.3 mm (range, 4 to 18 mm)
      preoperatively to average 1.4 mm (range, 0 to 6 mm) at last follow-up. Average
      Lysholm score of all patients was 72.7 +/- 8.8 (range, 54 to 79) preoperatively
      and significant improvement was seen, score was 92.2 +/- 5.3 (range, 74 to 97; p
      < 0.05) at last follow-up. Also IKDC score was normal in 35 cases, near normal in
      11 cases, abnormal in 1 case at last follow-up. CONCLUSIONS: Our new double
      bundle ACL reconstruction technique used hybrid fixation and Retroscrew had
      favorable outcomes.

PMID- 22162792
TI  - Long-term outcomes of ulnar shortening osteotomy for idiopathic ulnar impaction
      syndrome: at least 5-years follow-up.
AB  - BACKGROUND: There have been few outcomes studies with follow-up after performing
      ulnar shortening osteotomy for ulnar impaction syndrome. We investigated the long
      term clinical and radiological outcomes of ulnar shortening osteotomy for the
      treatment of idiopathic ulnar impaction syndrome. METHODS: We retrospectively
      reviewed 36 patients who had undergone ulnar shortening osteotomy for idiopathic
      ulnar impaction syndrome for a mean follow-up of 79.1 months (range, 62 to 132
      months). The modified Gartland and Werley scores were measured pre- and
      postoperatively. The radiographic parameters for the assessment of the distal
      radioulnar joint (DRUJ) as well as the relationship between these radiographic
      parameters and the clinical and radiological outcomes were determined. RESULTS:
      The average modified Gartland and Werley wrist score improved from 65.5 +/- 8.1
      preoperatively to 93.4 +/- 5.8 at the last follow-up visit. The average
      preoperative ulnar variance of 4.7 +/- 2.0 mm was reduced to an average of -0.6
      +/- 1.4 mm postoperatively. Osteoarthritic changes of the DRUJ were first seen at
      34.8 +/- 11.1 months follow-up in 6 of 36 wrists (16.7%). Those who had
      osteoarthritic changes in the DRUJ had significantly wider preoperative ulnar
      variance, a longer distal radioulnar distance and a greater length of ulnar
      shortening, but the wrist scores of the patients who had osteoarthritic changes
      in the DRUJ were comparable to those who did not have osteoarthritic changes in
      the DRUJ. CONCLUSIONS: The clinical outcomes are satisfactory for even more than
      5 years after ulnar shortening osteotomy for treating idiopathic ulnar impaction
      syndrome despite the osteoarthritic changes of the DRUJ. The patients who need a
      larger degree of ulnar shortening may develop DRUJ arthritis.

PMID- 22162793
TI  - Pediatric femoral neck fractures: our 10 years of experience.
AB  - BACKGROUND: Femoral neck fractures are rare injuries in children, but the high
      incidence of long term complications make it an important clinical entity. The
      aim of this retrospective study was to analyze the clinical outcomes of pediatric
      femur neck fractures that we managed over a 10 year period. METHODS: The study
      included 36 children (20 boys and 16 girls) who sustained femoral neck fractures
      and completed a minimum follow-up of one year. The children were treated either
      conservatively, or by open reduction and internal fixation (ORIF), or closed
      reduction and internal fixation (CRIF). The outcomes were analyzed using Ratliff
      criteria and a detailed record of complications was kept for all patients.
      RESULTS: The mean age of included patients was 10 years (range, 3 to 16 years)
      and the average follow-up was 3.2 years (range, 1.1 to 8.5 years). Based on
      Delbet's classification system, there were 0 type I (transepiphyseal), 16 type
      II, 11 type III, and 9 type IV fractures. There were 8 undisplaced fractures, 4
      of which later displaced after being managed initially in a hip spica. A
      satisfactory outcome was obtained in 27 (75%) children. Avascular necrosis (AVN)
      was the most common complication. It was seen in 7 of our patients, all of whom
      had an unsatisfactory outcome. Other complications included three cases each of
      coxa vara, non-union, and arthritic changes; and one case each of infection,
      primary screw perforation of head, and premature epiphyseal closure.
      Complications were lowest in the group treated by ORIF. Only 2 patients managed
      exclusively by conservative treatment ultimately achieved a satisfactory outcome.
      CONCLUSIONS: We believe that internal fixation of pediatric femoral neck
      fractures is preferred whenever feasible because conservative treatment carries a
      high risk of failure of reduction. Aggressive operative treatments aimed at
      anatomical reduction should be the goal and there should be no hesitation in
      choosing ORIF over CRIF. Outcome of patients is influenced primarily by
      development of AVN which occurs as an independent entity without much relation to
      the mode of treatment carried out.

PMID- 22162794
TI  - Physeal growth arrest by excessive compression: histological, biochemical, and
      micro-CT observations in rabbits.
AB  - BACKGROUND: Compressive force across the growth plate may cause retardation and
      even arrest of physeal growth. The purpose of this study was to investigate
      histologic changes, metabolic changes in terms of glycosaminoglycan (GAG)
      concentration, and contrast-enhanced micro-computed tomography (CEMCT) findings
      of physeal cartilage in a rabbit model of physeal damage caused by excessive
      compression. METHODS: Compressive forces were applied via external fixators for
      two weeks to the growth plates of distal femurs and proximal tibiae of right hind
      legs in 8-week-old rabbits. Left hind-legs remained intact and were used as
      controls. Forty-four bone specimens containing growth plates of distal femurs or
      proximal tibiae were harvested one week (n = 12) and four weeks (n = 32) after
      surgery, and examined for histologic findings (H&E staining) and GAGs
      quantification in physeal cartilage. After incubation in an ionic contrast
      material for 48 hours, specimens were scanned by CEMCT, and the pixel values of
      physeal cartilage were measured. RESULTS: CEMCT showed a thin, highly attenuated
      line parallel to the growth plate in compressed specimens harvested at four weeks
      after surgery, which was found to be transversely connected trabecular bone. In
      these specimens, GAG content in physeal cartilage was significantly lower, and
      CEMCT pixel values of physeal cartilage were significantly higher than in the
      specimens from the contralateral control side. CONCLUSIONS: Excessive compressive
      force applied to growth plates produces altered histologic features and metabolic
      function in terms of decreased GAG content in physeal cartilage, changes that can
      be demonstrated by CEMCT.

PMID- 22162795
TI  - Effect of hyaluronic acid-carboxymethylcellulose solution on perineural scar
      formation after sciatic nerve repair in rats.
AB  - BACKGROUND: Scar tissue formation is the major cause of failure in peripheral
      nerve surgery. Use of a hyaluronic acid-carboxymethylcellulose (HA-CMC) membrane
      (Seprafilm) as a solid anti-adhesion barrier agent is one of the therapeutic
      approaches to reduce postoperative scar tissue formation. However, a solid
      membrane may not be suitable for repair of a weak peripheral nerve site. This
      study examined the effect of HA-CMC solution on perineural scar formation after
      peripheral nerve repair in rats. METHODS: The sciatic nerves of 40 rats were
      transected and then immediately repaired using 10-0 nylon. The nerves were
      divided randomly into two groups. Saline and HA-CMC solution were applied
      topically to the nerve repair sites in the control and experimental groups,
      respectively. Reoperation was performed at 3, 6, 9, and 12 weeks to assess scar
      tissue formation. The assessment included the quality of wound healing, presence
      of perinueral adhesion, cellular components of the scar tissue, thickness of the
      scar tissue and histomorphological organization of the repair site. RESULTS:
      Topical application of the HA-CMC solution significantly decreased the
      macroscopic nerve adherence score and the numbers of the cellular components such
      as fibroblasts and inflammatory cells (p < 0.05, Mann-Whitney U-test). The scar
      tissue formation index was significantly lower in the experimental group at 12
      weeks than that in the control group (p < 0.05, Mann-Whitney U-test). The grading
      scores of the histomorphological axonal organization at the repair site were
      significantly higher in the experimental group than those in the control group at
      12 weeks (p < 0.05, Mann-Whitney U-test). No evidence of wound dehiscence or
      inflammatory reactions against the HA-CMC solution was noted. CONCLUSIONS:
      Topical application of a HA-CMC solution is effective in reducing the perineural
      scar formation and adhesion after sciatic nerve repair in rats, and is effective
      in promoting peripheral nerve regeneration at the repair site.

PMID- 22162797
TI  - Arthroscopic direct repair for a complete radial tear of the posterior root of
      the medial meniscus.
AB  - We report here on a new arthroscopic direct repair technique for a radial tear of
      the posterior root of the medial meniscus (PRMM) using a posterior trans-septal
      portal. Radial tears of the PRMM are commonly observed in the elderly population
      of Korea and Japan, and the life style of these people requires squatting and
      kneeling down in daily life. A radial tear of the PRMM results in the loss of
      hoop tension and this accelerates degenerative changes in the knee joint and
      causes early osteoarthritis. Several reports in the medical literature have
      focused on various repair techniques for these tears by using pull out sutures.
      These techniques result in nonanatomic fixation of the meniscus, which may lead
      to disturbed meniscal excursion and failure to restore hoop tension. Arthroscopic
      direct repair may contribute to restoring hoop tension and preventing accelerated
      degenerative changes in the knee joint of these patients.

PMID- 22162796
TI  - The effect of platelet rich plasma from bone marrow aspirate with added bone
      morphogenetic protein-2 on the Achilles tendon-bone junction in rabbits.
AB  - BACKGROUND: To determine if exogenously injected bone marrow derived platelet
      rich plasma (PRP) plus bone morphogenetic protein (BMP)-2 could accelerate the
      healing of bone-tendon junction injuries and increase the junction holding
      strength during the early regeneration period. METHODS: A direct injury model of
      the bone-tendon junction was made using an Achilles tendon-calcaneus bone
      junction in a rabbit. In the PRP/BMP-2/fibrin group, 0.05 mL of bone marrow
      derived PRP and 100 ng/mL of BMP-2 both incorporated into 0.1 mL of fibrin glue
      were injected into Achilles tendon-calcaneus bone junctions. The effect of the
      intervention was tested by comparing the results of an intervention group to a
      control group. The results of biomechanical testing, and histological and gross
      analyses were compared between the 2 groups at the following time points after
      surgery: 2 weeks, 4 weeks, and 8 weeks. RESULTS: Histologic examinations showed
      that woven bone developed in tendon-bone junctions at 2 weeks after surgery in
      the PRP/BMP-2/fibrin group. Mechanical test results showed no significant
      difference between the PRP/BMP-2/fibrin and control groups at 2 and 4 weeks after
      surgery, but the mean maximal load in the PRP/BMP-2/fibrin group was
      significantly higher than in the control group (p < 0.05) at 8 weeks after
      surgery. CONCLUSIONS: Bone marrow derived PRP and BMP-2 in fibrin glue
      accelerated healing in a rabbit model of tendon-bone junction injury.

PMID- 22162798
TI  - Femoral head fracture without dislocation by low-energy trauma in a young adult.
AB  - We describe the case of a healthy young man with a femoral head fracture by low
      energy trauma that occurred without evidence of hip dislocation. While plain
      radiographs showed no definite fracture or dislocation, computed tomography (CT)
      and magnetic resonance imaging (MRI) revealed a femoral head fracture with a
      wedge-shaped cortical depression at the superomedial aspect of the femoral head.
      Our patient reported feeling that the right hip had been displaced from its joint
      for a moment. This probably represented subluxation with spontaneous relocation.
      The characteristic findings and possible mechanisms of this fracture were
      postulated on the basis of the sequential 3 dimensional-CT and MRI. The clinical
      results of conservative treatment were better than those of previously reported
      indentation fractures.

PMID- 22162799
TI  - Psoas abscess caused by spontaneous rupture of colon cancer.
AB  - Spontaneous rupture of colon cancer, combined with psoas abscess formation, is
      rare. A 44-year-old male visited for back pain and left buttock mass. Abdominal
      computed tomography and magnetic resonance image revealed a large abscess in the
      left psoas muscle and in the left lower quadrant area. Ten days after incision
      and drainage, a skin defect around the left anterior superior iliac spine
      remained. A local flap was performed using a superficial skin graft. Ten days
      after the stitches had been removed, fecal discharge was observed around the
      anterior superior iliac spine at the flap site. An operation was performed by a
      general surgeon who had diagnosed this as a case of enterocutaneous fistula.
      Operative findings included a ruptured tumor mass in the descending colon, which
      was connected to a retroperitoneal abscess. Pathologic report findings determined
      adenocarcinoma of the resected colon. Herein, we report a case of psoas abscess
      resulting from perforating colon cancer.

PMID- 22162800
TI  - Diabetic peripheral microvascular complications: relationship to cognitive
      function.
AB  - Peripheral microvascular complications in diabetes are associated with concurrent
      cerebrovascular disease. As detailed cognitive assessment is not routinely
      carried out among diabetic patients, the aim was to establish whether the
      presence of clinical "peripheral" microvascular disease can identify a subgroup
      of patients with early evidence of cognitive impairment. Detailed psychometric
      assessment was performed in 23 diabetic patients with no microvascular
      complications (Group D), 27 diabetic patients with at least one microvascular
      complication: retinopathy, neuropathy, and/or nephropathy (Group DC), and 25
      healthy controls (Group H). Groups D and DC participants had significantly lower
      scores on reaction time (P = 0.003 and 0.0001, resp.) compared to controls.
      Similarly, groups D and DC participants had significantly lower scores on rapid
      processing of visual information (P = 0.034 and 0.001, resp.) compared to
      controls. In contrast, there was no significant difference between Groups D and
      DC on any of the cognitive areas examined. The results show that diabetes, in
      general, is associated with cognitive dysfunction, but the additional presence of
      peripheral microvascular disease does not add to cognitive decline. The study,
      however, indirectly supports the notion that the aetiology of cognitive
      impairment in diabetes may not be restricted to vascular pathology.

PMID- 22162801
TI  - A prospective study of lupus and rheumatoid arthritis in relation to deployment
      in support of iraq and afghanistan: the millennium cohort study.
AB  - The objective of this study was to prospectively assess the association between
      deployment in support of the operations in Iraq and Afghanistan and newly
      reported lupus and rheumatoid arthritis while also considering the effects of
      demographic, behavioral, and occupational characteristics. A total of 77,047
      (2001-2003) and 31,110 (2004-2006) participants completed the baseline Millennium
      Cohort questionnaire and were resurveyed approximately every 3 years.
      Longitudinal analyses were used to assess the adjusted association between
      deployment to Iraq and Afghanistan with and without combat exposures and newly
      reported disease. After adjusting, deployment was not significantly associated
      with newly reported lupus compared with nondeployers. However, compared with
      nondeployers, deployers with and without combat exposures were significantly less
      likely to newly report rheumatoid arthritis. Women, non-Hispanic black, and
      Hispanic participants had a significantly elevated risk for both diseases.
      Overall, deployment was not associated with an increased risk of newly reported
      lupus or rheumatoid arthritis.

PMID- 22162802
TI  - Still's Disease and Recurrent Complex Regional Pain Syndrome Type-I: The First
      Description.
AB  - Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder
      characterized by neuropathic pain associated with local edema and changes
      suggestive of autonomic involvement such as altered sweating, skin color, and
      skin temperature of the affected region. CRPS was described associated with
      several diseases, such as trauma, psychiatric conditions, and cancer. However, no
      case associated with Still's disease has been previously described. In this
      paper, the authors describe the first case of CRPS associated with Still's
      disease.

PMID- 22162804
TI  - Comparing Measures of Late HIV Diagnosis in Washington State.
AB  - As more US HIV surveillance programs routinely use late HIV diagnosis to monitor
      and characterize HIV testing patterns, there is an increasing need to standardize
      how late HIV diagnosis is measured. In this study, we compared two measures of
      late HIV diagnosis, one based on time between HIV and AIDS, the other based on
      initial CD4(+) results. Using data from Washington's HIV/AIDS Reporting System,
      we used multivariate logistic regression to identify predictors of late HIV
      diagnosis. We also conducted tests for trend to determine whether the proportion
      of cases diagnosed late has changed over time. Both measures lead us to similar
      conclusions about late HIV diagnosis, suggesting that being male, older, foreign
      born, or heterosexual increase the likelihood of late HIV diagnosis. Our findings
      reaffirm the validity of a time-based definition of late HIV diagnosis, while at
      the same time demonstrating the potential value of a lab-based measure.

PMID- 22162803
TI  - The Use of Bioinformatics for Studying HIV Evolutionary and Epidemiological
      History in South America.
AB  - The South American human immunodeficiency virus type 1 (HIV-1) epidemic is driven
      by several subtypes (B, C, and F1) and circulating and unique recombinant forms
      derived from those subtypes. Those variants are heterogeneously distributed
      around the continent in a country-specific manner. Despite some inconsistencies
      mainly derived from sampling biases and analytical constrains, most of studies
      carried out in the area agreed in pointing out specificities in the evolutionary
      dynamics of the circulating HIV-1 lineages. In this paper, we covered the
      theoretical basis, and the application of bioinformatics methods to reconstruct
      the HIV spatial-temporal dynamics, unveiling relevant information to understand
      the origin, geographical dissemination and the current molecular scenario of the
      HIV epidemic in the continent, particularly in the countries of Southern Cone.

PMID- 22162805
TI  - Rosiglitazone and fenofibrate additive effects on lipids.
AB  - Background. To evaluate the effect of rosiglitazone, fenofibrate, or their
      combined use on plasma lipids in normoglycemic healthy adults. Methods and
      Results. Subjects were randomized in a double-blind fashion to rosiglitazone +
      placebo, fenofibrate + placebo, rosiglitazone + fenofibrate, or matching double
      placebo. The between-group difference in the change in fasting TG, high-density
      lipoprotein cholesterol (HDL-C), LDL-C, and plasma apolipoproteins A-I, A-II, and
      C-III level were compared after 12 weeks of treatment. A total of 548 subjects
      were screened and 41 met the inclusion criteria. After 12 weeks of therapy, the
      median change in the triglyceride levels showed a significant reduction ranging
      from 47 to 55 mg per deciliter in the fenofibrate only and
      rosiglitazone/fenofibrate groups compared with placebo (P = 0.0496). However, the
      rosiglitazone only group did not show significant change in triglyceride level.
      The change in the Apo AII showed increase in all the treatment groups compared
      with placebo (P = 0.009). There was also significant change in the Apo CIII that
      showed reduction of its level in the fenofibrate only and
      rosiglitazone/fenofibrate groups (P = 0.0003). Conclusion. Rosiglitazone does not
      appear to modulate hypertriglyceridemia in patients with elevated triglycerides
      independent of glucose metabolism.

PMID- 22162807
TI  - The importance of social connectedness in building age-friendly communities.
AB  - The purpose of this paper is to further elucidate the importance of social
      relationships and social connectedness with aging in place and in developing
      elder-friendly communities. The process used in this study was inclusive of
      younger adults (age 40-65) as well as older adults (65+) in order to further
      understand how they envision a community that could support their own aging in
      place. A community forum, using the World Cafe format, was conducted in order to
      engage community members, 40 years and older, in conversation about the
      importance of social connectedness in elder-friendly communities. A second
      purpose of this forum was to obtain data on what would keep aging boomers in
      their community as they age. Three major themes emerged from qualitative analysis
      of the forum: social reciprocity, meaningful interactions, and structural
      needs/barriers. The results of this study reinforce the importance of social
      connectedness in creating and maintaining elder-friendly communities for older
      adults, as well as soon-to-be retired individuals, wishing to maintain life
      connectedness to their community. The study suggests the possibility of using
      more nontraditional research techniques (such as the World Cafe process) for
      gathering community level data.

PMID- 22162806
TI  - Comparative Structures and Evolution of Vertebrate Carboxyl Ester Lipase (CEL)
      Genes and Proteins with a Major Role in Reverse Cholesterol Transport.
AB  - Bile-salt activated carboxylic ester lipase (CEL) is a major triglyceride,
      cholesterol ester and vitamin ester hydrolytic enzyme contained within pancreatic
      and lactating mammary gland secretions. Bioinformatic methods were used to
      predict the amino acid sequences, secondary and tertiary structures and gene
      locations for CEL genes, and encoded proteins using data from several vertebrate
      genome projects. A proline-rich and O-glycosylated 11-amino acid C-terminal
      repeat sequence (VNTR) previously reported for human and other higher primate CEL
      proteins was also observed for other eutherian mammalian CEL sequences examined.
      In contrast, opossum CEL contained a single C-terminal copy of this sequence
      whereas CEL proteins from platypus, chicken, lizard, frog and several fish
      species lacked the VNTR sequence. Vertebrate CEL genes contained 11 coding exons.
      Evidence is presented for tandem duplicated CEL genes for the zebrafish genome.
      Vertebrate CEL protein subunits shared 53-97% sequence identities; demonstrated
      sequence alignments and identities for key CEL amino acid residues; and
      conservation of predicted secondary and tertiary structures with those previously
      reported for human CEL. Phylogenetic analyses demonstrated the relationships and
      potential evolutionary origins of the vertebrate CEL family of genes which were
      related to a nematode carboxylesterase (CES) gene and five mammalian CES gene
      families.

PMID- 22162808
TI  - Home and Community Environmental Features, Activity Performance, and Community
      Participation among Older Adults with Functional Limitations.
AB  - This paper describes relationships among home and community environmental
      features, activity performance in the home, and community participation potential
      to support aging in place. A subset of data on older adults with functional
      limitations (N = 122), sixty three (63) with mobility and 59 with other
      limitations, were utilized in this study from a larger project's subject pool.
      Results showed significant and positive correlations between environmental
      barriers, activity dependence and difficulty at home, and less community
      participation in the mobility limitation group. While kitchen and bathroom
      features were most limiting to home performance, bathtub or shower was the only
      home feature, and destination social environment was the only community feature,
      that explained community participation. Compared to environmental features, home
      performance explained much more community participation. Study results provide
      detailed information about environmental features as well as types of home
      activities that can be prioritized as interventions for aging in place.

PMID- 22162809
TI  - Families, friends, and the neighborhood of older adults: evidence from public
      housing in singapore.
AB  - Introduction. This empirical paper examines how the Housing Development Board
      (HDB) public housing neighborhood influences older urban Singaporeans' social
      interactions and ameliorates social isolation. Methods. Using 4,542 observations
      of noninstitutionalized urban adults aged 60 and above, ordered logistic
      regressions are run to determine the predictors of isolation while controlling
      for physical health and demographics. Results. 87% of older Singaporeans reside
      in public housing apartments while 13% reside in private market housing. The main
      predictor of social isolation is living alone and the second main predictor is
      coresidence with adult children. The relationship between coresidence with adult
      children and isolation is mediated when controlling for older adult functional
      limitations. The public apartment neighborhood and daily participation in public
      neighborhood events have substantial effects on reducing the risk of isolation.
      Older adult contact with friends alleviates isolation more than contact with non
      coresiding relatives. Conclusion. Findings suggest that the public neighborhood
      built environment in Singapore plays a positive role in the social interactions
      of the elderly. Knowledge of the factors that decrease the risk of social
      isolation will have implications for studying morbidity and mortality among the
      elderly.

PMID- 22162810
TI  - Aging adults and seasonal influenza: does the vitamin d status (h)arm the body?
AB  - Vitamin D (VitD), although originally described as an essential hormone for bone
      and mineral homeostasis, appears to have an active role in regulating specific
      facets of human immunity. Indeed, VitD has been shown to have significant effects
      on cytokine production and lymphocyte proliferation. Evidence that VitD affects
      clearance of selected pathogens is supported by epidemiological and clinical
      data, while its coadministration with influenza vaccine in mice enhanced both
      mucosal and systemic antibody responses. This paper aims to examine how VitD may
      contribute to limiting the burden of influenza infection in the aging and aged
      adults, a population in which this burden remains considerable. Furthermore, we
      discuss how VitD status may play a role in host resistance to influenza virus and
      influence the immunogenicity of the influenza vaccines currently licensed for
      adults aged 65 years or over by its effects on innate and adaptive immunities.

PMID- 22162811
TI  - Hypolipidemic Activity of Eryngium carlinae on Streptozotocin-Induced Diabetic
      Rats.
AB  - Diabetes mellitus (DM) is a significant risk factor for the development of
      cardiovascular complications. This study was undertaken to investigate the effect
      of chronic administration of ethanolic extract of Eryngium carlinae on glucose,
      creatinine, uric acid, total cholesterol, and triglycerides levels in serum of
      streptozotocin- (STZ-) induced diabetic rats. Triglycerides, total cholesterol,
      and uric acid levels increased in serum from diabetic rats. The treatment with E.
      carlinae prevented these changes. The administration of E. carlinae extract
      reduced the levels of creatinine, uric acid, total cholesterol, and
      triglycerides. Thus administration of E. carlinae is able to reduce
      hyperlipidemia related to the cardiovascular risk in diabetes mellitus.

PMID- 22162812
TI  - The natural history and clinical syndromes of degenerative cervical spondylosis.
AB  - Cervical spondylosis is a broad term which describes the age related chronic disc
      degeneration, which can also affect the cervical vertebrae, the facet and other
      joints and their associated soft tissue supports. Evidence of spondylitic change
      is frequently found in many asymptomatic adults. Radiculopathy is a result of
      intervertebral foramina narrowing. Narrowing of the spinal canal can result in
      spinal cord compression, ultimately resulting in cervical spondylosis myelopathy.
      This review article examines the current literature in relation to the cervical
      spondylosis and describes the three clinical syndromes of axial neck pain,
      cervical radiculopathy and cervical myelopathy.

PMID- 22162813
TI  - Preventing airborne disease transmission: review of methods for ventilation
      design in health care facilities.
AB  - Health care facility ventilation design greatly affects disease transmission by
      aerosols. The desire to control infection in hospitals and at the same time to
      reduce their carbon footprint motivates the use of unconventional solutions for
      building design and associated control measures. This paper considers indoor
      sources and types of infectious aerosols, and pathogen viability and infectivity
      behaviors in response to environmental conditions. Aerosol dispersion, heat and
      mass transfer, deposition in the respiratory tract, and infection mechanisms are
      discussed, with an emphasis on experimental and modeling approaches. Key building
      design parameters are described that include types of ventilation systems
      (mixing, displacement, natural and hybrid), air exchange rate, temperature and
      relative humidity, air flow distribution structure, occupancy, engineered
      disinfection of air (filtration and UV radiation), and architectural programming
      (source and activity management) for health care facilities. The paper describes
      major findings and suggests future research needs in methods for ventilation
      design of health care facilities to prevent airborne infection risk.

PMID- 22162814
TI  - Corneal topography from spectral optical coherence tomography (sOCT).
AB  - We present a method to obtain accurate corneal topography from a spectral optical
      coherence tomography (sOCT) system. The method includes calibration of the
      device, compensation of the fan (or field) distortion introduced by the scanning
      architecture, and image processing analysis for volumetric data extraction,
      segmentation and fitting. We present examples of three-dimensional (3-D) surface
      topography measurements on spherical and aspheric lenses, as well as on 10 human
      corneas in vivo. Results of sOCT surface topography (with and without fan
      distortion correction) were compared with non-contact profilometry (taken as
      reference) on a spherical lens, and with non-contact profilometry and state-of
      the art commercial corneal topography instruments on aspheric lenses and on
      subjects. Corneal elevation maps from all instruments were fitted by quadric
      surfaces (as well as by tenth-order Zernike polynomials) using custom routines.
      We found that the discrepancy in the estimated radius of curvature from nominal
      values in artificial corneas decreased from 4.6% (without fan distortion
      correction) to 1.6% (after fan distortion correction), and the difference in the
      asphericity decreased from 130% to 5%. In human corneas, the estimated corneal
      radius of curvature was not statistically significantly different across
      instruments. However, a Bland-Altman analysis showed consistent differences in
      the estimated asphericity and corneal shape between sOCT topographies without fan
      distortion correction and the rest of the measurements.

PMID- 22162815
TI  - Do different turbid media with matched bulk optical properties also exhibit
      similar polarization properties?
AB  - We here investigate polarimetric behavior of thick samples of porcine liver,
      Intralipid, and microsphere-based tissue phantoms whose absorption and scattering
      properties are matched. Using polarized light we measured reflection mode Mueller
      matrices and derived linear/circular/total depolarization rates, based on polar
      decomposition. According to our results, phantoms exhibit greater depolarization
      rates in the backscattering geometry than the liver sample. The enhanced tissue
      polarization preservation differs from previous reports of polarimetric
      transmission studies, with the likely cause of this difference being the angular
      dependence of the single-scattering phase function. Also, Intralipid approximated
      polarimetric liver behavior well, whereas the polystyrene phantoms did not.

PMID- 22162816
TI  - Blood testing at the single cell level using quantitative phase and amplitude
      microscopy.
AB  - It has recently been shown that quantitative phase imaging methods can provide
      clinically relevant parameters for red blood cell analysis with unprecedented
      detail and sensitivity. Since the quantitative phase information is dependent on
      both the thickness and refractive index, a major limitation to clinical
      translation has been a simple and practical approach to measure both
      simultaneously. Here we demonstrate both theoretically and experimentally that,
      by combining quantitative phase with a single absorption measurement, it is
      possible to measure both quantities at the single cell level. We validate this
      approach by comparing our results to those acquired using a clinical blood
      analyzer. This approach to decouple the thickness and refractive index for red
      blood cells may be used with any quantitative phase imaging method that can
      operate in tandem with bright field microscopy at the Soret-band wavelength.

PMID- 22162817
TI  - Video-rate fluorescence diffuse optical tomography for in vivo sentinel lymph
      node imaging.
AB  - We have developed a fiber-based, video-rate fluorescence diffuse optical
      tomography (DOT) system for noninvasive in vivo sentinel lymph node (SLN)
      mapping. Concurrent acquisition of fluorescence and reference signals allowed the
      efficient generation of ratio-metric data for 3D image reconstruction. Accurate
      depth localization and high sensitivity to fluorescent targets were established
      in to depths of >10 mm. In vivo accumulation of indocyanine green (ICG) dye was
      imaged in the region of the SLN following intradermal injection into the forepaw
      of rats. These results suggest that video-rate fluorescence DOT has significant
      potential as a clinical tool for noninvasive mapping of SLN.

PMID- 22162820
TI  - Quantification of cellular autofluorescence of human skin using multiphoton
      tomography and fluorescence lifetime imaging in two spectral detection channels.
AB  - We explore the diagnostic potential of imaging endogenous fluorophores using two
      photon microscopy and fluorescence lifetime imaging (FLIM) in human skin with two
      spectral detection channels. Freshly excised benign dysplastic nevi (DN) and
      malignant nodular Basal Cell Carcinomas (nBCCs) were excited at 760 nm. The
      resulting fluorescence signal was binned manually on a cell by cell basis. This
      improved the reliability of fitting using a double exponential decay model and
      allowed the fluorescence signatures from different cell populations within the
      tissue to be identified and studied. We also performed a direct comparison
      between different diagnostic groups. A statistically significant difference
      between the median mean fluorescence lifetime of 2.79 ns versus 2.52 ns (blue
      channel, 300-500 nm) and 2.08 ns versus 1.33 ns (green channel, 500-640 nm) was
      found between nBCCs and DN respectively, using the Mann-Whitney U test (p <
      0.01). Further differences in the distribution of fluorescence lifetime
      parameters and inter-patient variability are also discussed.

PMID- 22162819
TI  - Modeling diffuse reflectance from homogeneous semi-infinite turbid media for
      biological tissue applications: a Monte Carlo study.
AB  - Diffuse reflectance spectroscopy is one of the simplest and widely used
      techniques for the non-invasive study of biological tissues but no exact
      analytical solution exists for the problem of diffuse reflectance from turbid
      media such as biological tissues. In this work, a general treatment of the
      problem of diffuse reflectance from a homogeneous semi-infinite turbid medium is
      presented using Monte Carlo simulations. Based on the results of the Monte Carlo
      method, simple semi-empirical analytical solutions are developed valid for a wide
      range of collection geometries corresponding to various optical detector
      diameters. This approach may be useful for the quick and accurate modeling of
      diffuse reflectance from tissues.

PMID- 22162818
TI  - Influence of titanium dioxide nanoparticles on skin surface temperature at
      sunlight irradiation.
AB  - In this paper, we report about simulated distribution of density of absorbed
      light energy within human skin following light illumination with a combination of
      three wavelengths (310, 514 and 800 nm) with ratios similar to ultraviolet,
      visible and infrared fractions of the solar irradiance spectrum. We study heat
      distribution within the skin treated with a sunscreen containing TiO(2)
      nanoparticles. Our results show that administration of TiO(2) particles does not
      cause heat load on the tissue.

PMID- 22162821
TI  - Improving wavefront boundary condition for in vivo high resolution adaptive
      optics ophthalmic imaging.
AB  - An ophthalmic adaptive optics (AO) imaging system is especially affected by pupil
      edge effects due to the higher noise and aberration level at the edge of the
      human pupil as well as the impact of head and eye motions on the pupil. In this
      paper, a two-step approach was proposed and implemented for reducing the edge
      effects and improving wavefront slope boundary condition. First, given an imaging
      pupil, a smaller size of sampling aperture can be adopted to avoid the noisy
      boundary slope data. To do this, we calibrated a set of influence matrices for
      different aperture sizes to accommodate pupil variations within the population.
      In step two, the slope data was extrapolated from the less noisy slope data
      inside the pupil towards the outside such that we had reasonable slope data over
      a larger aperture to stabilize the impact of eye pupil dynamics. This technique
      is applicable to any Neumann boundary-based active /adaptive modality but it is
      especially useful in the eye for improving AO retinal image quality where the
      boundary positions fluctuate.

PMID- 22162822
TI  - Characterization of optical properties of ZnO nanoparticles for quantitative
      imaging of transdermal transport.
AB  - Widespread applications of ZnO nanoparticles (NP) in sun-blocking cosmetic
      products have raised safety concerns related to their potential transdermal
      penetration and resultant cytotoxicity. Nonlinear optical microscopy provides
      means for high-contrast imaging of ZnO NPs lending in vitro and in vivo
      assessment of the nanoparticle uptake in skin, provided their nonlinear optical
      properties are characterized. We report on this characterization using ZnO NP
      commercial product, Zinclear, mean-sized 21 nm. Two-photon action cross-section
      of this bandgap material (E(bg) = 3.37 eV, lambda(bg) = 370 nm) measured by two
      techniques yielded consistent results of [Formula: see text] = 6.2 +/- 0.8 MUGM
      at 795 nm, and 32 +/- 6 MUGM at 770 nm per unit ZnO crystal cell, with the
      quantum efficiency of [Formula: see text] = (0.9 +/- 0.2) %. In order to
      demonstrate the quantitative imaging, nonlinear optical microscopy images of the
      excised human skin topically treated with Zinclear were acquired and processed
      using [Formula: see text] and [Formula: see text]values yielding nanoparticle
      concentration map in skin. Accumulations of Zinclear ZnO nanoparticles were
      detected only on the skin surface and in skin folds reaching concentrations of
      800 NPs per MUm(3).

PMID- 22162823
TI  - Improvement of image quality of time-domain diffuse optical tomography with l
      sparsity regularization.
AB  - An l(p) (0 < p <= 1) sparsity regularization is applied to time-domain diffuse
      optical tomography with a gradient-based nonlinear optimization scheme to improve
      the spatial resolution and the robustness to noise. The expression of the l(p)
      sparsity regularization is reformulated as a differentiable function of a
      parameter to avoid the difficulty in calculating its gradient in the optimization
      process. The regularization parameter is selected by the L-curve method.
      Numerical experiments show that the l(p) sparsity regularization improves the
      spatial resolution and recovers the difference in the absorption coefficients
      between two targets, although a target with a small absorption coefficient may
      disappear due to the strong effect of the l(p) sparsity regularization when the
      value of p is too small. The l(p) sparsity regularization with small p values
      strongly localizes the target, and the reconstructed region of the target becomes
      smaller as the value of p decreases. A phantom experiment validates the numerical
      simulations.

PMID- 22162824
TI  - Depth dependence of vascular fluorescence imaging.
AB  - In vivo surface imaging of fluorescently labeled vasculature has become a widely
      used tool for functional brain imaging studies. Techniques such as
      phosphorescence quenching for oxygen tension measurements and indocyanine green
      fluorescence for vessel perfusion monitoring rely on surface measurements of
      vascular fluorescence. However, the depth dependence of the measured fluorescence
      signals has not been modeled in great detail. In this paper, we investigate the
      depth dependence of the measured signals using a three-dimensional Monte Carlo
      model combined with high resolution vascular anatomy. We found that a bulk
      vascularization assumption to modeling the depth dependence of the signal does
      not provide an accurate picture of penetration depth of the collected
      fluorescence signal in most cases. Instead the physical distribution of
      microvasculature, the degree of absorption difference between extravascular and
      intravascular space, and the overall difference in absorption at the excitation
      and emission wavelengths must be taken into account to determine the depth
      penetration of the fluorescence signal. Additionally, we found that using
      targeted illumination can provide for superior surface vessel sensitivity over
      wide-field illumination, with small area detection offering an even greater
      amount of sensitivity to surface vasculature. Depth sensitivity can be enhanced
      by either increasing the detector area or increasing the illumination area.
      Finally, we see that excitation wavelength and vessel size can affect intra
      vessel sampling distribution, as well as the amount of signal that originates
      from inside the vessel under targeted illumination conditions.

PMID- 22162825
TI  - Noninvasive detection of filaggrin gene mutations using Raman spectroscopy.
AB  - Knowledge of the existence of filaggrin (FLG) gene mutations might be helpful for
      a subclassification of patients with atopic dermatitis (AD) which can be used to
      introduce individualized treatments. In this work the filaggrin content in the
      skin is assessed using Raman spectroscopy and the results are compared to FLG
      genotyping of Mexican-mestizo patients. Results showed that the 2282del4 and
      R501X mutations present in the European population but absent in people of Asian
      or African descent are also present in the Mexican-mestizo population. The
      results also showed that patients with filaggrin gene mutations presented lower
      filaggrin concentrations measured using the vector correlation of their skin
      Raman spectra and a fixed spectrum of pure human recombinant filaggrin, these
      results indicate that Raman spectroscopy may be used as a noninvasive tool to
      detect FLG gene mutations.

PMID- 22162826
TI  - Spatiotemporal relations of primary sensorimotor and secondary motor activation
      patterns mapped by NIR imaging.
AB  - Functional near infrared (fNIR) imaging was used to identify spatiotemporal
      relations between spatially distinct cortical regions activated during various
      hand and arm motion protocols. Imaging was performed over a field of view (FOV,
      12 x 8.4 cm) including the secondary motor, primary sensorimotor, and the
      posterior parietal cortices over a single brain hemisphere. This is a more
      extended FOV than typically used in current fNIR studies. Three subjects
      performed four motor tasks that induced activation over this extended FOV. The
      tasks included card flipping (pronation and supination) that, to our knowledge,
      has not been performed in previous functional magnetic resonance imaging (fMRI)
      or fNIR studies. An earlier rise and a longer duration of the hemodynamic
      activation response were found in tasks requiring increased physical or mental
      effort. Additionally, analysis of activation images by cluster component analysis
      (CCA) demonstrated that cortical regions can be grouped into clusters, which can
      be adjacent or distant from each other, that have similar temporal activation
      patterns depending on whether the performed motor task is guided by visual or
      tactile feedback. These analyses highlight the future potential of fNIR imaging
      to tackle clinically relevant questions regarding the spatiotemporal relations
      between different sensorimotor cortex regions, e.g. ones involved in the
      rehabilitation response to motor impairments.

PMID- 22162827
TI  - Nomarski serial time-encoded amplified microscopy for high-speed contrast
      enhanced imaging of transparent media.
AB  - High-speed high-contrast imaging modalities that enable image acquisition of
      transparent media without the need for chemical staining are essential tools for
      a broad range of applications; from semiconductor process monitoring to blood
      screening. Here we introduce a method for contrast-enhanced imaging of unstained
      transparent objects that is capable of high-throughput imaging. This method
      combines the Nomarski phase contrast capability with the ultrahigh frame rate and
      shutter speed of serial time-encoded amplified microscopy. As a proof of concept,
      we show imaging of a transparent test structure and white blood cells in flow at
      a shutter speed of 33 ps and a frame rate of 36.1 MHz using a single-pixel photo
      detector. This method is expected to be a valuable tool for high-throughput
      screening of unstained cells.

PMID- 22162828
TI  - Pretreatment metabotype as a predictor of response to sertraline or placebo in
      depressed outpatients: a proof of concept.
AB  - The purpose of this study was to determine whether the baseline metabolic profile
      (that is, metabotype) of a patient with major depressive disorder (MDD) would
      define how an individual will respond to treatment. Outpatients with MDD were
      randomly assigned to sertraline (up to 150 mg per day) (N=43) or placebo (N=46)
      in a double-blind 4-week trial. Baseline serum samples were profiled using the
      liquid chromatography electrochemical array; the output was digitized to create a
      'digital map' of the entire measurable response for a particular sample. Response
      was defined as >=50% reduction baseline to week 4 in the 17-item Hamilton Rating
      Scale for Depression total score. Models were built using the one-out method for
      cross-validation. Multivariate analyses showed that metabolic profiles partially
      separated responders and non-responders to sertraline or to placebo. For the
      sertraline models, the overall correct classification rate was 81% whereas it was
      72% for the placebo models. Several pathways were implicated in separation of
      responders and non-responders on sertraline and on placebo including
      phenylalanine, tryptophan, purine and tocopherol. Dihydroxyphenylacetic acid,
      tocopherols and serotonin were common metabolites in separating responders and
      non-responders to both drug and placebo. Pretreatment metabotypes may predict
      which depressed patients will respond to acute treatment (4 weeks) with
      sertraline or placebo. Some pathways were informative for both treatments whereas
      other pathways were unique in predicting response to either sertraline or
      placebo. Metabolomics may inform the biochemical basis for the early efficacy of
      sertraline.

PMID- 22162829
TI  - Evolutionary genetic dissection of human interferons.
AB  - Interferons (IFNs) are cytokines that play a key role in innate and adaptive
      immune responses. Despite the large number of immunological studies of these
      molecules, the relative contributions of the numerous IFNs to human survival
      remain largely unknown. Here, we evaluated the extent to which natural selection
      has targeted the human IFNs and their receptors, to provide insight into the
      mechanisms that govern host defense in the natural setting. We found that some
      IFN-alpha subtypes, such as IFN-alpha6, IFN-alpha8, IFN-alpha13, and IFN-alpha14,
      as well as the type II IFN-gamma, have evolved under strong purifying selection,
      attesting to their essential and nonredundant function in immunity to infection.
      Conversely, selective constraints have been relaxed for other type I IFNs,
      particularly for IFN-alpha10 and IFN-epsilon, which have accumulated missense or
      nonsense mutations at high frequencies within the population, suggesting
      redundancy in host defense. Finally, type III IFNs display geographically
      restricted signatures of positive selection in European and Asian populations,
      indicating that genetic variation at these genes has conferred a selective
      advantage to the host, most likely by increasing resistance to viral infection.
      Our population genetic analyses show that IFNs differ widely in their biological
      relevance, and highlight evolutionarily important determinants of host immune
      responsiveness.

PMID- 22162830
TI  - Autophagy in antigen-presenting cells results in presentation of citrullinated
      peptides to CD4 T cells.
AB  - Antibody responses to citrullinated self-proteins are found in autoimmunities,
      particularly in rheumatoid arthritis, where they serve as a diagnostic indicator.
      We show here that processing of the protein hen egg-white lysozyme (HEL) resulted
      in citrullination of peptides presented on class II MHC molecules by antigen
      presenting cells. The presentation of the citrullinated peptides but not of the
      unmodified peptides was associated with autophagy. Dendritic cells (DCs),
      macrophages, and thymic DCs presented citrullinated peptides constitutively.
      Their treatment with 3-methyladenine (3MA) blocked presentation of citrullinated
      HEL peptides, but presentation of unmodified peptides was not affected.
      Presentation of citrullinated peptides was not detected on B cells or B lymphoma
      cells under normal culture conditions. In B cells, engagement of the B cell
      antigen receptor was required for presentation of the citrullinated peptides,
      also inhibited by 3MA. B lymphoma-expressing HEL cells presented citrullinated
      peptides only after brief serum starvation. This presentation was reduced by 3MA
      or by reduction in Atg5 expression. Presentation of the unmodified peptides was
      not changed. The findings indicate a linkage between autophagy and autoreactivity
      through the generation of this neo-epitope.

PMID- 22162831
TI  - ETV6 mutations in early immature human T cell leukemias.
AB  - Early immature T cell acute lymphoblastic leukemias (T-ALLs) account for ~5-10%
      of pediatric T-ALLs and are associated with poor prognosis. However, the genetic
      defects that drive the biology of these tumors remain largely unknown. In this
      study, analysis of microarray gene expression signatures in adult T-ALL
      demonstrated a high prevalence of early immature leukemias and revealed a close
      relationship between these tumors and myeloid leukemias. Many adult immature T
      ALLs harbored mutations in myeloid-specific oncogenes and tumor suppressors
      including IDH1, IDH2, DNMT3A, FLT3, and NRAS. Moreover, we identified ETV6
      mutations as a novel genetic lesion uniquely present in immature adult T-ALL. Our
      results demonstrate that early immature adult T-ALL represents a heterogeneous
      category of leukemias characterized by the presence of overlapping myeloid and T
      ALL characteristics, and highlight the potential role of ETV6 mutations in these
      tumors.

PMID- 22162832
TI  - Guanylate binding protein 1 is a novel effector of EGFR-driven invasion in
      glioblastoma.
AB  - Although GBP1 (guanylate binding protein 1) was among the first interferon
      inducible proteins identified, its function is still largely unknown. Epidermal
      growth factor receptor (EGFR) activation by amplification or mutation is one of
      the most frequent genetic lesions in a variety of human tumors. These include
      glioblastoma multiforme (GBM), which is characterized by independent but
      interrelated features of extensive invasion into normal brain parenchyma, rapid
      growth, necrosis, and angiogenesis. In this study, we show that EGFR activation
      promoted GBP1 expression in GBM cell lines through a signaling pathway involving
      Src and p38 mitogen-activated protein kinase. Moreover, we identified YY1 (Yin
      Yang 1) as the downstream transcriptional regulator regulating EGFR-driven GBP1
      expression. GBP1 was required for EGFR-mediated MMP1 (matrix metalloproteinase 1)
      expression and glioma cell invasion in vitro. Although deregulation of GBP1
      expression did not affect glioma cell proliferation, overexpression of GBP1
      enhanced glioma cell invasion through MMP1 induction, which required its C
      terminal helical domain and was independent of its GTPase activity. Reducing GBP1
      levels by RNA interference in invasive GBM cells also markedly inhibited their
      ability to infiltrate the brain parenchyma of mice. GBP1 expression was high and
      positively correlated with EGFR expression in human GBM tumors and cell lines,
      particularly those of the neural subtype. Together, these findings establish GBP1
      as a previously unknown link between EGFR activity and MMP1 expression and
      nominate it as a novel potential therapeutic target for inhibiting GBM invasion.

PMID- 22162833
TI  - Memory B cells, but not long-lived plasma cells, possess antigen specificities
      for viral escape mutants.
AB  - Memory B cells (MBCs) and long-lived plasma cells (LLPCs) persist after clearance
      of infection, yet the specific and nonredundant role MBCs play in subsequent
      protection is unclear. After resolution of West Nile virus infection in mice, we
      demonstrate that LLPCs were specific for a single dominant neutralizing epitope,
      such that immune serum poorly inhibited a variant virus that encoded a mutation
      at this critical epitope. In contrast, a large fraction of MBC produced antibody
      that recognized both wild-type (WT) and mutant viral epitopes. Accordingly,
      antibody produced by the polyclonal pool of MBC neutralized WT and variant
      viruses equivalently. Remarkably, we also identified MBC clones that recognized
      the mutant epitope better than the WT protein, despite never having been exposed
      to the variant virus. The ability of MBCs to respond to variant viruses in vivo
      was confirmed by experiments in which MBCs were adoptively transferred or
      depleted before secondary challenge. Our data demonstrate that class-switched MBC
      can respond to variants of the original pathogen that escape neutralization of
      antibody produced by LLPC without a requirement for accumulating additional
      somatic mutations.

PMID- 22162848
TI  - An integrative modeling approach to elucidate suction-feeding performance.
AB  - Research on suction-feeding performance has mostly focused on measuring
      individual underlying components such as suction pressure, flow velocity, ram or
      the effects of suction-induced forces on prey movement during feeding. Although
      this body of work has advanced our understanding of aquatic feeding, no consensus
      has yet emerged on how to combine all of these variables to predict prey-capture
      performance. Here, we treated the aquatic predator-prey encounter as a
      hydrodynamic interaction between a solid particle (representing the prey) and the
      unsteady suction flows around it, to integrate the effects of morphology,
      physiology, skull kinematics, ram and fluid mechanics on suction-feeding
      performance. We developed the suction-induced force-field (SIFF) model to study
      suction-feeding performance in 18 species of centrarchid fishes, and asked what
      morphological and functional traits underlie the evolution of feeding performance
      on three types of prey. Performance gradients obtained using SIFF revealed that
      different trait combinations contribute to the ability to feed on attached,
      evasive and (strain-sensitive) zooplanktonic prey because these prey types impose
      different challenges on the predator. The low overlap in the importance of
      different traits in determining performance also indicated that the evolution of
      suction-feeding ability along different ecological axes is largely unconstrained.
      SIFF also yielded estimates of feeding ability that performed better than
      kinematic traits in explaining natural patterns of prey use. When compared with
      principal components describing variation in the kinematics of suction-feeding
      events, SIFF output explained significantly more variation in centrarchid diets,
      suggesting that the inclusion of more mechanistic hydrodynamic models holds
      promise for gaining insight into the evolution of aquatic feeding performance.

PMID- 22162849
TI  - The occurrence of two types of fast skeletal myosin heavy chains from abdominal
      muscle of kuruma shrimp Marsupenaeus japonicus and their different tissue
      distribution.
AB  - Shrimps belong to the class Crustacea, which forms a large, diverse group in the
      invertebrates. However, the physiology and biochemistry of their skeletal muscles
      have been poorly understood compared with those from vertebrates including
      mammals and fish. The present study focused on myosin, the major protein in
      skeletal muscle, from adult specimens of kuruma shrimp Marsupenaeus japonicus.
      Two types of the gene encoding myosin heavy chain (MHC), a large subunit of the
      myosin molecule, were cloned from abdominal fast skeletal muscle and defined as
      MHCa and MHCb. Protein analysis revealed that the MHCa isoform was expressed at a
      higher level than the MHCb isoform. The full-length cDNA clones of MHCa and MHCb
      consisted of 5929 bp and 5955 bp, respectively, which encoded 1912 and 1910 amino
      acids, respectively. Both were classified into fast muscle type by comparison
      with the partially deduced amino acid sequences of fast-type and slow-type (S(1),
      slow twitch) MHCs reported previously for the American lobster Homarus
      americanus. The amino acid identities between MHCa and MHCb of kuruma shrimp were
      78%, 60% and 72% in the regions of subfragment-1, subfragment-2 and light
      meromyosin, respectively, and 71% in total. In situ hybridisation using anti
      sense RNA-specific probes, along with northern blot analysis using different
      tissues from abdominal muscle, revealed the different localisation of MHCa and
      MHCb transcripts in abdominal fast skeletal muscle, suggesting their distinct
      physiological functions.

PMID- 22162850
TI  - Oxygen utilization and the branchial pressure gradient during ram ventilation of
      the shortfin mako, Isurus oxyrinchus: is lamnid shark-tuna convergence
      constrained by elasmobranch gill morphology?
AB  - Ram ventilation and gill function in a lamnid shark, the shortfin mako, Isurus
      oxyrinchus, were studied to assess how gill structure may affect the lamnid-tuna
      convergence for high-performance swimming. Despite differences in mako and tuna
      gill morphology, mouth gape and basal swimming speeds, measurements of mako O(2)
      utilization at the gills (53.4+/-4.2%) and the pressure gradient driving
      branchial flow (96.8+/-26.1 Pa at a mean swimming speed of 38.8+/-5.8 cm s(-1))
      are similar to values reported for tunas. Also comparable to tunas are estimates
      of the velocity (0.22+/-0.03 cm s(-1)) and residence time (0.79+/-0.14 s) of
      water though the interlamellar channels of the mako gill. However, mako and tuna
      gills differ in the sites of primary branchial resistance. In the mako,
      approximately 80% of the total branchial resistance resides in the septal
      channels, structures inherent to the elasmobranch gill that are not present in
      tunas. The added resistance at this location is compensated by a correspondingly
      lower resistance at the gill lamellae accomplished through wider interlamellar
      channels. Although greater interlamellar spacing minimizes branchial resistance,
      it also limits lamellar number and results in a lower total gill surface area for
      the mako relative to tunas. The morphology of the elasmobranch gill thus appears
      to constrain gill area and, consequently, limit mako aerobic performance to less
      than that of tunas.

PMID- 22162851
TI  - Interactive effects of salinity and elevated CO2 levels on juvenile eastern
      oysters, Crassostrea virginica.
AB  - Rising levels of atmospheric CO(2) lead to acidification of the ocean and alter
      seawater carbonate chemistry, which can negatively impact calcifying organisms,
      including mollusks. In estuaries, exposure to elevated CO(2) levels often co
      occurs with other stressors, such as reduced salinity, which enhances the
      acidification trend, affects ion and acid-base regulation of estuarine calcifiers
      and modifies their response to ocean acidification. We studied the interactive
      effects of salinity and partial pressure of CO(2) (P(CO2)) on biomineralization
      and energy homeostasis in juveniles of the eastern oyster, Crassostrea virginica,
      a common estuarine bivalve. Juveniles were exposed for 11 weeks to one of two
      environmentally relevant salinities (30 or 15 PSU) either at current atmospheric
      P(CO2) (~400 MUatm, normocapnia) or P(CO2) projected by moderate IPCC scenarios
      for the year 2100 (~700-800 MUatm, hypercapnia). Exposure of the juvenile oysters
      to elevated P(CO2) and/or low salinity led to a significant increase in
      mortality, reduction of tissue energy stores (glycogen and lipid) and negative
      soft tissue growth, indicating energy deficiency. Interestingly, tissue ATP
      levels were not affected by exposure to changing salinity and P(CO2), suggesting
      that juvenile oysters maintain their cellular energy status at the expense of
      lipid and glycogen stores. At the same time, no compensatory upregulation of
      carbonic anhydrase activity was found under the conditions of low salinity and
      high P(CO2). Metabolic profiling using magnetic resonance spectroscopy revealed
      altered metabolite status following low salinity exposure; specifically, acetate
      levels were lower in hypercapnic than in normocapnic individuals at low salinity.
      Combined exposure to hypercapnia and low salinity negatively affected mechanical
      properties of shells of the juveniles, resulting in reduced hardness and fracture
      resistance. Thus, our data suggest that the combined effects of elevated P(CO2)
      and fluctuating salinity may jeopardize the survival of eastern oysters because
      of weakening of their shells and increased energy consumption.

PMID- 22162852
TI  - Ants might use different view-matching strategies on and off the route.
AB  - Individual foraging ants are known to rely on views of their surroundings for
      route learning and for pinpointing goals. Different strategies have been proposed
      to explain how ants might process visual information for navigation, but little
      is known about the actual development and nature of the view-based strategies
      used by ants in complex natural environments. Here, we constrained the knowledge
      of Melophorus bagoti ants to either the nest vicinity or a curved route (length
      10 m) and analysed their initial direction when released at both novel and
      familiar locations. In parallel, we used 360 deg pictures of the scene as a basis
      for modelling different navigational strategies. We propose here a new hypothesis
      based on skyline height comparison to explain how ants home from novel locations.
      Interestingly, this strategy succeeded well at novel locations but failed on
      familiar terrain. By contrast, the use of a visual compass strategy failed at
      novel locations but could explain the results on familiar routes. We suggest that
      ants might switch between skyline height comparison and a visual compass
      strategy, depending on whether they are on familiar terrain or not. How ants
      could switch between strategies and how their memories develop are discussed in
      turn.

PMID- 22162853
TI  - A robotic fish caudal fin: effects of stiffness and motor program on locomotor
      performance.
AB  - We designed a robotic fish caudal fin with six individually moveable fin rays
      based on the tail of the bluegill sunfish, Lepomis macrochirus. Previous fish
      robotic tail designs have loosely resembled the caudal fin of fishes, but have
      not incorporated key biomechanical components such as fin rays that can be
      controlled to generate complex tail conformations and motion programs similar to
      those seen in the locomotor repertoire of live fishes. We used this robotic
      caudal fin to test for the effects of fin ray stiffness, frequency and motion
      program on the generation of thrust and lift forces. Five different sets of fin
      rays were constructed to be from 150 to 2000 times the stiffness of biological
      fin rays, appropriately scaled for the robotic caudal fin, which had linear
      dimensions approximately four times larger than those of adult bluegill sunfish.
      Five caudal fin motion programs were identified as kinematic features of swimming
      behaviors in live bluegill sunfish, and were used to program the kinematic
      repertoire: flat movement of the entire fin, cupping of the fin, W-shaped fin
      motion, fin undulation and rolling movements. The robotic fin was flapped at
      frequencies ranging from 0.5 to 2.4 Hz. All fin motions produced force in the
      thrust direction, and the cupping motion produced the most thrust in almost all
      cases. Only the undulatory motion produced lift force of similar magnitude to the
      thrust force. More compliant fin rays produced lower peak magnitude forces than
      the stiffer fin rays at the same frequency. Thrust and lift forces increased with
      increasing flapping frequency; thrust was maximized by the 500* stiffness fin
      rays and lift was maximized by the 1000* stiffness fin rays.

PMID- 22162854
TI  - Contextual chemosensory urine signaling in an African cichlid fish.
AB  - Chemosensory signaling is crucial for communication in many fish species, but
      little is known about how signalers modulate chemical output in response to
      sensory information and social context. Here, we tested the hypothesis that
      dominant male African cichlid fish (Astatotilapia burtoni) use urine signals
      during social interactions, and demonstrate that this signaling depends on social
      context (reproductive; territorial) and on available sensory information (visual
      cues; full interaction). We injected males with dye to visualize urine pulses and
      exposed them to full sensory information or visual cues alone of four types: (1)
      dominant male; (2) gravid (reproductively receptive) females; (3) mouth-brooding
      (non-receptive) females; or (4) control (no fish). We found that males released
      urine sooner and increased their urination frequency when visually exposed to
      gravid females as compared with mouth-brooding females and or no-fish controls.
      While males could distinguish female reproductive states using visual cues alone,
      courtship behavior rates were ~10-fold higher when they fully interacted with
      gravid females compared with receiving visual cues alone. Males also increased
      their urination and territorial behaviors when exposed to another male,
      suggesting that chemical signals may convey information on dominance status.
      These data support the hypothesis that dominant males use urine as a chemical
      signal and adjust the frequency of their urine output based on contextual
      information.

PMID- 22162855
TI  - An analysis of the rebound of the body in backward human running.
AB  - Step frequency and energy expenditure are greater in backward running than in
      forward running. The differences in the motion of the centre of mass of the body
      associated with these findings are not known. These differences were measured
      here on nine trained subjects during backward and forward running steps on a
      force platform at 3-17 km h(-1). In contrast to previous reports, we found that
      the maximal upward acceleration of the centre of mass and the aerial phase,
      averaged over the whole speed range, are greater in backward running than in
      forward running (15.7 versus 13.2 m s(-2), P=1.9*10(-6) and 0.098 versus 0.072 s,
      P=2.4*10(-5), respectively). Opposite to forward running, the impulse on the
      ground is directed more vertically during the push at the end of stance than
      during the brake at the beginning of stance. The higher step frequency in
      backward running is explained by a greater mass-specific vertical stiffness of
      the bouncing system (499 versus 352 s(-2), P=2.3*10(-11)) resulting in a shorter
      duration of the lower part of the vertical oscillation of the centre of mass when
      the force is greater than body weight, with a similar duration of the upper part
      when the force is lower than body weight. As in a catapult, muscle-tendon units
      are stretched more slowly during the brake at the beginning of stance and shorten
      more rapidly during the push at the end of stance. We suggest that the catapult
      like mechanism of backward running, although requiring greater energy expenditure
      and not providing a smoother ride, may allow a safer stretch-shorten cycle of
      muscle-tendon units.

PMID- 22162856
TI  - Vocal tract articulation revisited: the case of the monk parakeet.
AB  - Birdsong and human speech share many features with respect to vocal learning and
      development. However, the vocal production mechanisms have long been considered
      to be distinct. The vocal organ of songbirds is more complex than the human
      larynx, leading to the hypothesis that vocal variation in birdsong originates
      mainly at the sound source, while in humans it is primarily due to vocal tract
      filtering. However, several recent studies have indicated the importance of vocal
      tract articulators such as the beak and oropharyngeal-esophageal cavity. In
      contrast to most other bird groups, parrots have a prominent tongue, raising the
      possibility that tongue movements may also be of significant importance in vocal
      production in parrots, but evidence is rare and observations often anecdotal. In
      the current study we used X-ray cinematographic imaging of naturally vocalizing
      monk parakeets (Myiopsitta monachus) to assess which articulators are possibly
      involved in vocal tract filtering in this species. We observed prominent tongue
      height changes, beak opening movements and tracheal length changes, which
      suggests that all of these components play an important role in modulating vocal
      tract resonance. Moreover, the observation of tracheal shortening as a vocal
      articulator in live birds has to our knowledge not been described before. We also
      found strong positive correlations between beak opening and amplitude as well as
      changes in tongue height and amplitude in several types of vocalization. Our
      results suggest considerable differences between parrot and songbird vocal
      production while at the same time the parrot's vocal articulation might more
      closely resemble human speech production in the sense that both make extensive
      use of the tongue as a vocal articulator.

PMID- 22162857
TI  - Hypoxia tolerance in elasmobranchs. I. Critical oxygen tension as a measure of
      blood oxygen transport during hypoxia exposure.
AB  - The critical O(2) tension of whole-animal O(2) consumption rate (M(O2)), or
      P(crit), is the water P(O2) (Pw(O(2))) at which an animal transitions from an
      oxyregulator to an oxyconformer. Although P(crit) is a popular measure of hypoxia
      tolerance in fishes because it reflects the capacity for O(2) uptake from the
      environment at low Pw(O(2)), little is known about the interrelationships between
      P(crit) and blood O(2) transport characteristics and increased use of anaerobic
      metabolism during hypoxia exposure in fishes, especially elasmobranchs. We
      addressed this knowledge gap using progressive hypoxia exposures of two
      elasmobranch species with differing hypoxia tolerance. The P(crit) of the hypoxia
      tolerant epaulette shark (Hemiscyllium ocellatum, 5.10+/-0.37 kPa) was
      significantly lower than that of the comparatively hypoxia-sensitive shovelnose
      ray (Aptychotrema rostrata, 7.23+/-0.40 kPa). Plasma [lactate] was elevated above
      normoxic values at around P(crit) in epaulette sharks, but increased relative to
      normoxic values at Pw(O(2)) below P(crit) in shovelnose rays, providing equivocal
      support for the hypothesis that P(crit) is associated with increased anaerobic
      metabolism. The M(O2), arterial P(O2) and arterial blood O(2) content (Ca(O(2)))
      were similar between the two species under normoxia and decreased in both species
      with progressive hypoxia, but as Pw(O(2)) declined, epaulette sharks had a
      consistently higher M(O2) and Ca(O(2)) than shovelnose rays, probably due to
      their significantly greater in vivo haemoglobin (Hb)-O(2) binding affinity (in
      vivo Hb-O(2) P(50)=4.27+/-0.57 kPa for epaulette sharks vs 6.35+/-0.34 kPa for
      shovelnose rays). However, at Pw(O(2)) values representing the same percentage of
      each species' P(crit) (up to ~175% of P(crit)), Hb-O(2) saturation and Ca(O(2))
      were similar between species. These data support the hypothesis that Hb-O(2)
      P(50) is an important determinant of P(crit) and suggest that P(crit) can predict
      Hb-O(2) saturation and Ca(O(2)) during hypoxia exposure, with a lower P(crit)
      being associated with greater O(2) supply at a given Pw(O(2)) and consequently
      better hypoxia tolerance. Thus, P(crit) is a valuable predictor of environmental
      hypoxia tolerance and hypoxia exposures standardized at a given percentage of
      P(crit) will yield comparable levels of arterial hypoxaemia, facilitating cross
      species comparisons of responses to hypoxia.

PMID- 22162858
TI  - Hypoxia tolerance in elasmobranchs. II. Cardiovascular function and tissue
      metabolic responses during progressive and relative hypoxia exposures.
AB  - Cardiovascular function and metabolic responses of the heart and other tissues
      during hypoxia exposure were compared between the hypoxia-tolerant epaulette
      shark (Hemiscyllium ocellatum) and the hypoxia-sensitive shovelnose ray
      (Aptychotrema rostrata). In both species, progressive hypoxia exposure caused
      increases in stroke volume and decreases in heart rate, cardiac output, cardiac
      power output (CPO, an assessment of cardiac energy demand) and dorsal aortic
      blood pressure, all of which occurred at or below each species' critical P(O2)
      for whole-animal O(2) consumption rate, M(O2) (P(crit)). In epaulette sharks,
      which have a lower P(crit) than shovelnose rays, routine levels of cardiovascular
      function were maintained to lower water P(O2) levels and the changes from routine
      levels during hypoxia exposure were smaller compared with those for the
      shovelnose ray. The maintenance rather than depression of cardiovascular function
      during hypoxia exposure may contribute to the superior hypoxia tolerance of the
      epaulette shark, presumably by improving O(2) delivery and waste removal.
      Compared with shovelnose rays, epaulette sharks were also better able to maintain
      a stable cardiac high-energy phosphate pool and to minimize metabolic acidosis
      and lactate accumulation in the heart (despite higher CPO) and other tissues
      during a 4 h exposure to 40% of their respective P(crit) (referred to as a
      relative hypoxia exposure), which results in similar hypoxaemia in the two
      species (~16% Hb-O(2) saturation). These different metabolic responses to
      relative hypoxia exposure suggest that variation in hypoxia tolerance among
      species is not solely dictated by differences in O(2) uptake and transport but
      also by tissue-specific metabolic responses. In particular, lower tissue
      [lactate] accumulation in epaulette sharks than in shovelnose rays during
      relative hypoxia exposure suggests that enhanced extra-cardiac metabolic
      depression occurs in the former species. This could facilitate strategic
      utilization of available O(2) for vital organs such as the heart, potentially
      explaining the greater hypoxic cardiovascular function of epaulette sharks.

PMID- 22162859
TI  - Electromyography of wrist and finger flexor muscles in olive baboons (Papio
      anubis).
AB  - Some non-human primates use digitigrade hand postures when walking slowly on the
      ground. As a component of an extended limb, a digitigrade posture can help
      minimize wrist joint moments thereby requiring little force production directly
      from wrist flexors (and/or from the assistance of finger flexors) to maintain
      limb posture. As a consequence, less active muscle volume would be required from
      these anti-gravity muscles and overall metabolic costs associated with locomotion
      could be reduced. To investigate whether the use of digitigrade hand postures
      during walking in primates entails minimal use of anti-gravity muscles, this
      study examined electromyography (EMG) patterns in both the wrist and finger
      flexor muscles in facultatively digitigrade olive baboons (Papio anubis) across a
      range of speeds. The results demonstrate that baboons can adopt a digitigrade
      hand posture when standing and moving at slow speeds without requiring
      substantial EMG activity from distal anti-gravity muscles. Higher speed
      locomotion, however, entails increasing EMG activity and is accompanied by a
      dynamic shift to a more palmigrade-like limb posture. Thus, the ability to adopt
      a digitigrade hand posture by monkeys is an adaptation for ground living, but it
      was never co-opted for fast locomotion. Rather, digitigrady in primates appears
      to be related to energetic efficiency for walking long distances.

PMID- 22162860
TI  - Regulation of behaviorally associated gene networks in worker honey bee ovaries.
AB  - Several lines of evidence support genetic links between ovary size and division
      of labor in worker honey bees. However, it is largely unknown how ovaries
      influence behavior. To address this question, we first performed transcriptional
      profiling on worker ovaries from two genotypes that differ in social behavior and
      ovary size. Then, we contrasted the differentially expressed ovarian genes with
      six sets of available brain transcriptomes. Finally, we probed behavior-related
      candidate gene networks in wild-type ovaries of different sizes. We found
      differential expression in 2151 ovarian transcripts in these artificially
      selected honey bee strains, corresponding to approximately 20.3% of the predicted
      gene set of honey bees. Differences in gene expression overlapped significantly
      with changes in the brain transcriptomes. Differentially expressed genes were
      associated with neural signal transmission (tyramine receptor, TYR) and
      ecdysteroid signaling; two independently tested nuclear hormone receptors (HR46
      and ftz-f1) were also significantly correlated with ovary size in wild-type bees.
      We suggest that the correspondence between ovary and brain transcriptomes
      identified here indicates systemic regulatory networks among hormones (juvenile
      hormone and ecdysteroids), pheromones (queen mandibular pheromone), reproductive
      organs and nervous tissues in worker honey bees. Furthermore, robust correlations
      between ovary size and neuraland endocrine response genes are consistent with the
      hypothesized roles of the ovaries in honey bee behavioral regulation.

PMID- 22162861
TI  - Point of no return in diving emperor penguins: is the timing of the decision to
      return limited by the number of strokes?
AB  - At some point in a dive, breath-hold divers must decide to return to the surface
      to breathe. The issue of when to end a dive has been discussed intensively in
      terms of foraging ecology and behavioral physiology, using dive duration as a
      temporal parameter. Inevitably, however, a time lag exists between the decision
      of animals to start returning to the surface and the end of the dive, especially
      in deep dives. In the present study, we examined the decision time in emperor
      penguins under two different conditions: during foraging trips at sea and during
      dives at an artificial isolated dive hole. It was found that there was an upper
      limit for the decision-to-return time irrespective of dive depth in birds diving
      at sea. However, in a large proportion of dives at the isolated dive hole, the
      decision-to-return time exceeded the upper limit at sea. This difference between
      the decision times in dives at sea versus the isolated dive hole was accounted
      for by a difference in stroke rate. The stroke rates were much lower in dives at
      the isolated hole and were inversely correlated with the upper limit of decision
      times in individual birds. Unlike the decision time to start returning, the
      cumulative number of strokes at the decision time fell within a similar range in
      the two experiments. This finding suggests that the number of strokes, but not
      elapsed time, constrained the decision of emperor penguins to return to the
      surface. While the decision to return and to end a dive may be determined by a
      variety of ecological, behavioral and physiological factors, the upper limit to
      that decision time may be related to cumulative muscle workload.

PMID- 22162862
TI  - Earliest ciliary swimming effects vertical transport of planktonic embryos in
      turbulence and shear flow.
AB  - Eggs released by broadcast-spawning marine invertebrates are often negatively
      buoyant. Blastulae and gastrulae of these species are commonly motile, with
      passive stability that leads to upward swimming in still water. The earliest
      occurrence of swimming in developing embryos of diverse invertebrates may
      therefore permit vertical migration in nature. I used turbulent and laminar shear
      flows to investigate: (1) the speed and direction of transport of non-motile and
      newly swimming stages of the echinoids Dendraster excentricus and
      Strongylocentrotus purpuratus in turbulence, and (2) the limit of stable vertical
      orientation in swimming blastulae of D. excentricus. Swimming contributed
      significantly to the rate of upward transport of D. excentricus in turbulence
      experiments where the kinetic energy dissipation rate (epsilon) was ~10(-2) cm(2)
      s(-3). However, swimming significantly reduced the rate of upward transport of S.
      purpuratus blastulae in turbulence, suggesting that passively stable swimmers of
      this species were turned from the vertical, crossed flow-lines, and migrated into
      downwelling. Observations of swimming in laminar shear indicate that D.
      excentricus swimming blastulae maintain a vertical orientation until shear
      approaches 0.26 s(-1), equivalent to sub-microscale shear in turbulence where
      epsilon is ~10(-3) cm(2) s(-3). Swimming speeds of D. excentricus showed an
      unexpected dependence on shear, indicating that greater shear (within limits) can
      enhance speed of ciliary swimming. In D. excentricus, swimming by newly hatched
      blastulae should support upward migration in turbulence characteristic of coastal
      surface waters, whereas species differences in passive stability and swimming
      responses to shear may lead to differences in vertical transport and subsequent
      dispersal.

PMID- 22162863
TI  - Local acoustic particle motion guides sound-source localization behavior in the
      plainfin midshipman fish, Porichthys notatus.
AB  - Sound-source localization behavior was studied in the plainfin midshipman fish
      (Porichthys notatus) by making use of the naturally occurring phonotaxis response
      of gravid females to playback of the male's advertisement call. The observations
      took place outdoors in a circular concrete tank. A dipole sound projector was
      placed at the center of the tank and an 80-90 Hz tone (the approximate
      fundamental frequency to the male's advertisement call) was broadcast to gravid
      females that were released from alternative sites approximately 100 cm from the
      source. The phonotaxic responses of females to the source were recorded, analyzed
      and compared with the sound field. One release site was approximately along the
      vibratory axis of the dipole source, and the other was approximately orthogonal
      to the vibratory axis. The sound field in the tank was fully characterized
      through measurements of the sound pressure field using hydrophones and acoustic
      particle motion using an accelerometer. These measurements confirmed that the
      sound field was a nearly ideal dipole. When released along the dipole vibratory
      axis, the responding female fish took essentially straight paths to the source.
      However, when released approximately 90 deg to the source's vibratory axis, the
      responding females took highly curved paths to the source that were approximately
      in line with the local particle motion axes. These results indicate that the
      acoustic cues used by fish during sound-source localization include the axes of
      particle motion of the local sound field.

PMID- 22162864
TI  - The energetics of running stability: costs of transport in grass-cutting ants
      depend on fragment shape.
AB  - Grass-cutting ants (Atta vollenweideri) carry fragments that can be many times
      heavier and longer than the ants themselves and it is important for them to avoid
      falling over during load transport. To investigate whether the energetic costs of
      transport are affected by the need to maintain stability, the rate of CO(2)
      production was measured in both unladen workers and workers carrying standardized
      paper fragments of different size and shape. We tested: (1) the effect of mass by
      comparing workers carrying either light or heavy fragments of the same size, and
      (2) the effect of shape by comparing short and long fragments of the same mass.
      Consistent with previous studies, metabolic rate increased but running speed
      remained constant when ants carried heavier fragments. The net cost of transport
      (normalized to the total mass of ant and fragment) was the same for heavy and
      light fragments, and did not differ from the costs of carrying a unit body mass.
      Ants carrying long fragments showed similar metabolic rates but ran significantly
      slower than ants carrying short fragments. As a consequence, net cost of
      transport was significantly higher for long fragments than for short ones, and
      higher than the costs of carrying a unit body mass. The observed reduction in
      running speed is likely a result of the ants' need to maintain stability. When
      the absolute costs of transport were compared, smaller ants required more energy
      to carry heavier and longer fragments than larger workers, but the opposite was
      found for lighter and shorter fragments. The absolute costs of transport per unit
      fragment mass suggest that it is energetically advantageous for a colony to
      allocate smaller workers for the transport of small fragments and larger workers
      for large fragments. The present results underline the importance of
      biomechanical factors for the understanding of leaf-cutting ant foraging
      strategies.

PMID- 22162866
TI  - Surface roughness effects on attachment ability of the spider Philodromus dispar
      (Araneae, Philodromidae).
AB  - The morphology of the tarsal attachment system of the running spider Philodromus
      dispar Walckenaer 1826 (Araneae, Philodomidae) was studied using scanning
      electron microscopy and its performance was experimentally tested in traction
      force measurements. Each pretarsus bears a hierarchically built hairy adhesive
      pad that consists of a dense array of flattened setae covered with numerous
      microtrichia on the substrate-facing side. Microtrichia carry spatulate end tips
      that allow close contact with the substrate. Forces were estimated on tethered
      living specimens on rough epoxy resin surfaces (asperity size 0.3, 1, 3, 9 and 12
      MUm) and on a smooth surface as a control. A strong reduction in adhesion was
      observed for substrates with an asperity size of 0.3 and 1 MUm. Comparison of the
      present data with previous results of different organisms demonstrates that the
      difference in force reduction on rough substrata depends on the dimensions of
      terminal contact elements (spatulae).

PMID- 22162865
TI  - High levels of dietary fat impair glucose homeostasis in rainbow trout.
AB  - This study was designed to assess the effects of dietary fat levels on glucose
      homeostasis in rainbow trout under prolonged hyperglycaemia induced by high
      carbohydrate intake. Trout were fed identical amounts of one of two iso-energetic
      diets containing either a low (LFD, 3%) or a high fat level (HFD, 20%) and
      similar amounts of digestible carbohydrates (26-30%) for 14 days. While a single
      high fat meal reduced glycaemia compared with a low fat meal, the consumption of
      a high fat diet for 14 days resulted in prolonged hypergylcaemia and reduced
      plasma glucose clearance in response to an exogenous glucose or insulin
      challenge. The hyperglycaemic phenotype in trout was characterised by a reduction
      of the activities of lipogenic and glucose phosphorylating enzymes with a
      concomitant stimulation of enzymes involved in glucose production in the liver
      and reduced glycogen levels in the white muscle. Impaired glucose tolerance (IGT)
      was further associated with a significant reduction of insulin receptor substrate
      1 (IRS1) protein content in muscle, and with a poor response of HFD fed fish to
      an exogenous insulin load, suggestive of impaired insulin signalling in trout fed
      with a HFD. To our knowledge, this is the first study showing that a teleost can
      also develop a high fat-induced IGT, characterised by persistent hyperglycaemia
      and reduced insulin sensitivity, established symptoms of IGT and the prediabetic
      insulin-resistant state in mammals. Our results also provide evidence that
      persistent hyperglycaemia after a high carbohydrate meal stems from a metabolic
      interaction between dietary macronutrients rather than from high carbohydrate
      intake alone.

PMID- 22162867
TI  - Selected regulation of gastrointestinal acid-base secretion and tissue metabolism
      for the diamondback water snake and Burmese python.
AB  - Snakes exhibit an apparent dichotomy in the regulation of gastrointestinal (GI)
      performance with feeding and fasting; frequently feeding species modestly
      regulate intestinal function whereas infrequently feeding species rapidly
      upregulate and downregulate intestinal function with the start and completion of
      each meal, respectively. The downregulatory response with fasting for
      infrequently feeding snakes is hypothesized to be a selective attribute that
      reduces energy expenditure between meals. To ascertain the links between feeding
      habit, whole-animal metabolism, and GI function and metabolism, we measured
      preprandial and postprandial metabolic rates and gastric and intestinal acid-base
      secretion, epithelial conductance and oxygen consumption for the frequently
      feeding diamondback water snake (Nerodia rhombifer) and the infrequently feeding
      Burmese python (Python molurus). Independent of body mass, Burmese pythons
      possess a significantly lower standard metabolic rate and respond to feeding with
      a much larger metabolic response compared with water snakes. While fasting,
      pythons cease gastric acid and intestinal base secretion, both of which are
      stimulated with feeding. In contrast, fasted water snakes secreted gastric acid
      and intestinal base at rates similar to those of digesting snakes. We observed no
      difference between fasted and fed individuals for either species in gastric or
      intestinal transepithelial potential and conductance, with the exception of a
      significantly greater gastric transepithelial potential for fed pythons at the
      start of titration. Water snakes experienced no significant change in gastric or
      intestinal metabolism with feeding. Fed pythons, in contrast, experienced a near
      doubling of gastric metabolism and a tripling of intestinal metabolic rate. For
      fasted individuals, the metabolic rate of the stomach and small intestine was
      significantly lower for pythons than for water snakes. The fasting downregulation
      of digestive function for pythons is manifested in a depressed gastric and
      intestinal metabolism, which selectively serves to reduce basal metabolism and
      hence promote survival between infrequent meals. By maintaining elevated GI
      performance between meals, fasted water snakes incur the additional cost of
      tissue activity, which is expressed in a higher standard metabolic rate.

PMID- 22162868
TI  - Synergistic repression of the embryonic programme by SET DOMAIN GROUP 8 and
      EMBRYONIC FLOWER 2 in Arabidopsis seedlings.
AB  - The seed maturation programme occurs only during the late phase of embryo
      development, and repression of the maturation genes is pivotal for seedling
      development. However, mechanisms that repress the expression of this programme in
      vegetative tissues are not well understood. A genetic screen was performed for
      mutants that express maturation genes in leaves. Here, it is shown that mutations
      affecting SDG8 (SET DOMAIN GROUP 8), a putative histone methyltransferase, cause
      ectopic expression of a subset of maturation genes in leaves. Further, to
      investigate the relationship between SDG8 and the Polycomb Group (PcG) proteins,
      which are known to repress many developmentally important genes including seed
      maturation genes, double mutants were made and formation of somatic embryos was
      observed on mutant seedlings with mutations in both SDG8 and EMF2 (EMBRYONIC
      FLOWER 2). Analysis of histone methylation status at the chromatin sites of a
      number of maturation loci revealed a synergistic effect of emf2 and sdg8 on the
      deposition of the active histone mark which is the trimethylation of Lys4 on
      histone 3 (H3K4me3). This is consistent with high expression of these genes and
      formation of somatic embryos in the emf2 sdg8 double mutants. Interestingly, a
      double mutant of sdg8 and vrn2 (vernalization2), a paralogue of EMF2, grew and
      developed normally to maturity. These observations demonstrate a functional
      cooperative interplay between SDG8 and an EMF2-containing PcG complex in
      maintaining vegetative cell identity by repressing seed genes to promote seedling
      development. The work also indicates the functional specificities of PcG
      complexes in Arabidopsis.

PMID- 22162869
TI  - Comparative effects of deficit irrigation and alternate partial root-zone
      irrigation on xylem pH, ABA and ionic concentrations in tomatoes.
AB  - Comparative effects of partial root-zone irrigation (PRI) and deficit irrigation
      (DI) on xylem pH, ABA, and ionic concentrations of tomato (Lycopersicon
      esculentum L.) plants were investigated in two split-root pot experiments.
      Results showed that PRI plants had similar or significantly higher xylem pH,
      which was increased by 0.2 units relative to DI plants. Nitrate and total ionic
      concentrations (cations+anions), and the proportion of cations influenced xylem
      pH such that xylem pH increases as nitrate and total ionic concentrations
      decrease, and the proportion of cations increases. In most cases, the xylem ABA
      concentration was similar for PRI and DI plants, and a clear association between
      increases in xylem pH with increasing xylem ABA concentration was only found when
      the soil water content was relatively low. The concentrations of anions, cations,
      and the sum of anions and cations in PRI were higher than in the DI treatment
      when soil water content was relatively high in the wetted soil compartment.
      However, when water content in both soil compartments of the PRI pots were very
      low before the next irrigation, the acquisition of nutrients by roots was
      reduced, resulting in lower concentrations of anions and cations in the PRI than
      in the DI treatment. It is therefore essential that the soil water content in the
      wet zone should be maintained relatively high while that in the drying soil zone
      should not be very low, both conditions are crucial to maintain high soil and
      plant water status while sustaining ABA signalling of the plants.

PMID- 22162871
TI  - Xanthophyll cycle pigment and antioxidant profiles of winter-red (anthocyanic)
      and winter-green (acyanic) angiosperm evergreen species.
AB  - Leaves of many angiosperm evergreen species change colour from green to red
      during winter, corresponding with the synthesis of anthocyanin pigments. The
      ecophysiological function of winter colour change (if any), and why it occurs in
      some species and not others, are not yet understood. It was hypothesized that
      anthocyanins play a compensatory photoprotective role in species with limited
      capacity for energy dissipation. Seasonal xanthophyll pigment content,
      chlorophyll fluorescence, leaf nitrogen, and low molecular weight antioxidants
      (LMWA) of five winter-red and five winter-green angiosperm evergreen species were
      compared. Our results showed no difference in seasonal xanthophyll pigment
      content (V+A+Z g(-1) leaf dry mass) or LMWA between winter-red and winter-green
      species, indicating red-leafed species are not deficient in their capacity for
      non-photochemical energy dissipation via these mechanisms. Winter-red and winter
      green species also did not differ in percentage leaf nitrogen, corroborating
      previous studies showing no difference in seasonal photosynthesis under
      saturating irradiance. Consistent with a photoprotective function of anthocyanin,
      winter-red species had significantly lower xanthophyll content per unit
      chlorophyll and less sustained photoinhibition than winter-green species (i.e.
      higher pre-dawn F(v)/F(m) and a lower proportion of de-epoxidized xanthophylls
      retained overnight). Red-leafed species also maintained a higher maximum quantum
      yield efficiency of PSII at midday (F'(v)/F'(m)) during winter, and showed
      characteristics of shade acclimation (positive correlation between anthocyanin
      and chlorophyll content, and negative correlation with chlorophyll a/b). These
      results suggest that the capacity for photon energy dissipation (photochemical
      and non-photochemical) is not limited in red-leafed species, and that
      anthocyanins more likely function as an alternative photoprotective strategy to
      increased VAZ/Chl during winter.

PMID- 22162872
TI  - How genetic modification of roots affects rhizosphere processes and plant
      performance.
AB  - Genetic modification of plants has become common practice. However, root-specific
      genetic modifications have only recently been advocated. Here, a review is
      presented regarding how root-specific modifications can have both plant internal
      and rhizosphere-mediated effects on aboveground plant properties and plant
      performance. Plant internal effects refer to pleiotropic processes such as
      transportation of the modified gene product. Rhizosphere-mediated effects refer
      to altered plant-rhizosphere interactions, which subsequently feed back to the
      plant. Such plant-soil feedback mechanisms have been demonstrated both in natural
      systems and in crops. Here how plant internal and rhizosphere-mediated effects
      could enhance or counteract improvements in plant properties for which the
      genetic modification was intended is discussed. A literature survey revealed that
      rice is the most commonly studied crop species in the context of root-specific
      transgenesis, predominantly in relation to stress tolerance. Phytoremediation, a
      process in which plants are used to clean up pollutants, is also often an
      objective when transforming roots. These two examples are used to review
      potential effects of root genetic modifications on shoots. There are several
      examples in which root-specific genetic modifications only lead to better plant
      performance if the genes are specifically expressed in roots. Constitutive
      expression can even result in modified plants that perform worse than non
      modified plants. Rhizosphere effects have rarely been examined, but clearly
      genetic modification of roots can influence rhizosphere interactions, which in
      turn can affect shoot properties. Indeed, field studies with root-transformed
      plants frequently show negative effects on shoots that are not seen in laboratory
      studies. This might be due to the simplified environments that are used in
      laboratories which lack the full range of plant-rhizosphere interactions that are
      present in the field.

PMID- 22162873
TI  - Sulphur limitation and early sulphur deficiency responses in poplar: significance
      of gene expression, metabolites, and plant hormones.
AB  - The influence of sulphur (S) depletion on the expression of genes related to S
      metabolism, and on metabolite and plant hormone contents was analysed in young
      and mature leaves, fine roots, xylem sap, and phloem exudates of poplar (Populus
      tremula*Populus alba) with special focus on early consequences. S depletion was
      applied by a gradual decrease of sulphate availability. The observed changes were
      correlated with sulphate contents. Based on the decrease in sulphate contents,
      two phases of S depletion could be distinguished that were denominated as 'S
      limitation' and 'early S deficiency'. S limitation was characterized by improved
      sulphate uptake (enhanced root-specific sulphate transporter PtaSULTR1;2
      expression) and reduction capacities (enhanced adenosine 5'-phosphosulphate (APS)
      reductase expression) and by enhanced remobilization of sulphate from the vacuole
      (enhanced putative vacuolar sulphate transporter PtaSULTR4;2 expression). During
      early S deficiency, whole plant distribution of S was impacted, as indicated by
      increasing expression of the phloem-localized sulphate transporter PtaSULTR1;1
      and by decreasing glutathione contents in fine roots, young leaves, mature
      leaves, and phloem exudates. Furthermore, at 'early S deficiency', expression of
      microRNA395 (miR395), which targets transcripts of PtaATPS3/4 (ATP sulphurylase)
      for cleavage, increased. Changes in plant hormone contents were observed at
      'early S deficiency' only. Thus, S depletion affects S and plant hormone
      metabolism of poplar during 'S limitation' and 'early S deficiency' in a time
      series of events. Despite these consequences, the impact of S depletion on growth
      of poplar plants appears to be less severe than in Brassicaceae such as
      Arabidopsis thaliana or Brassica sp.

PMID- 22162876
TI  - Thickness Dependent Characteristics of High Permittivity PMN-0.32PT Single
      Crystal for High Frequency Medical Imaging Applications.
AB  - The dielectric, piezoelectric, and acoustic properties of PMN-0.32PT
      (Pb(Mg(1/3)Nb(2/3)) O(3)-PbTiO(3)) single crystals were investigated as a
      function of sample thickness ranging from 120 to 30 MUm in order to enlighten the
      origin of property degradation of crystals for high frequency ultrasound
      applications. Electromechanical coupling factor(k(t) ), clamped and free
      dielectric constants decreased but sound velocity increased with decreasing
      crystal thickness. Particularly, repoling of the PMN-PT crystals would bring
      about a noteworthy enhancement in electromechanical and dielectric properties,
      which urges the importance of PMN-PT as a promising piezoelectric material for
      high frequency ultrasound transducers.

PMID- 22162875
TI  - The morning after: alcohol misuse and employment problems.
AB  - Using a rich, recent, and nationally representative longitudinal survey
      specifically designed to examine alcohol use and associated problems, we
      investigate the effects of alcohol misuse on a series of understudied and perhaps
      less common employment problems. Such problems include being fired or laid off
      from a job, sustained unemployment, and conflicts with a supervisor and/or co
      worker. After controlling for time-invariant omitted variables via fixed effects
      estimation, we find evidence that three measures of alcohol misuse are
      significantly related to employment problems. The results offer new information
      on the potential adverse labor market effects of alcohol misuse and shed light on
      potential mechanisms through which alcohol misuse may impact intensive labor
      supply and/or wages.

PMID- 22162870
TI  - Metabolic routes affecting rubber biosynthesis in Hevea brasiliensis latex.
AB  - The cytosolic mevalonate (MVA) pathway in Hevea brasiliensis latex is the
      conventionally accepted pathway which provides isopentenyl diphosphate (IPP) for
      cis-polyisoprene (rubber) biosynthesis. However, the plastidic 2-C-methyl-D
      erythritol 4-phosphate (MEP) pathway may be an alternative source of IPP since
      its more recent discovery in plants. Quantitative RT-PCR (qRT-PCR) expression
      profiles of genes from both pathways in latex showed that subcellular
      compartmentalization of IPP for cis-polyisoprene synthesis is related to the
      degree of plastidic carotenoid synthesis. From this, the occurrence of two
      schemes of IPP partitioning and utilization within one species is proposed
      whereby the supply of IPP for cis-polyisoprene from the MEP pathway is related to
      carotenoid production in latex. Subsequently, a set of latex unique gene
      transcripts was sequenced and assembled and they were then mapped to IPP
      requiring pathways. Up to eight such pathways, including cis-polyisoprene
      biosynthesis, were identified. Our findings on pre- and post-IPP metabolic routes
      form an important aspect of a pathway knowledge-driven approach to enhancing cis
      polyisoprene biosynthesis in transgenic rubber trees.

PMID- 22162874
TI  - Identification, functional characterization, and regulation of the enzyme
      responsible for floral (E)-nerolidol biosynthesis in kiwifruit (Actinidia
      chinensis).
AB  - Flowers of the kiwifruit species Actinidia chinensis produce a mixture of
      sesquiterpenes derived from farnesyl diphosphate (FDP) and monoterpenes derived
      from geranyl diphosphate (GDP). The tertiary sesquiterpene alcohol (E)-nerolidol
      was the major emitted volatile detected by headspace analysis. Contrastingly, in
      solvent extracts of the flowers, unusually high amounts of (E,E)-farnesol were
      observed, as well as lesser amounts of (E)-nerolidol, various farnesol and
      farnesal isomers, and linalool. Using a genomics-based approach, a single gene
      (AcNES1) was identified in an A. chinensis expressed sequence tag library that
      had significant homology to known floral terpene synthase enzymes. In vitro
      characterization of recombinant AcNES1 revealed it was an enzyme that could
      catalyse the conversion of FDP and GDP to the respective (E)-nerolidol and
      linalool terpene alcohols. Enantiomeric analysis of both AcNES1 products in vitro
      and floral terpenes in planta showed that (S)-(E)-nerolidol was the predominant
      enantiomer. Real-time PCR analysis indicated peak expression of AcNES1 correlated
      with peak (E)-nerolidol, but not linalool accumulation in flowers. This result,
      together with subcellular protein localization to the cytoplasm, indicated that
      AcNES1 was acting as a (S)-(E)-nerolidol synthase in A. chinensis flowers. The
      synthesis of high (E,E)-farnesol levels appears to compete for the available pool
      of FDP utilized by AcNES1 for sesquiterpene biosynthesis and hence strongly
      influences the accumulation and emission of (E)-nerolidol in A. chinensis
      flowers.

PMID- 22162878
TI  - Health care reform and comparative effectiveness research in critical care
      medicine.

PMID- 22162877
TI  - Gene - Environment Interplay, Family Relationships, and Child Adjustment.
AB  - This paper reviews behavioral genetic research from the past decade that has
      moved beyond simply studying the independent influences of genes and
      environments. The studies considered in this review have instead focused on
      understanding gene - environment interplay, including genotype - environment
      correlation ( rGE) and genotype * environment interaction (G * E). Studies have
      suggested that rGE is an important pathway through which family relationships are
      associated with child adjustment. Also important are direct causal influences of
      family relationships on child adjustment, independent of genetic confounds. Other
      studies have indicated that genetic and environmental influences on child
      adjustment are moderated by different levels of family relationships in G * E
      interactions. Genetically informed studies that have examined family relations
      have been critical to advancing our understanding of gene - environment
      interplay.

PMID- 22162879
TI  - Long-acting beta-agonists and asthma: the saga continues.

PMID- 22162880
TI  - The Hispanic paradox unraveled?

PMID- 22162881
TI  - Endotoxemia before and after surgical repair for congenital heart disease.

PMID- 22162882
TI  - Regulatory T cells and lung fibrosis: a good cell gone bad.

PMID- 22162883
TI  - Two, one, or none for chronic obstructive pulmonary disease: who decides and how?

PMID- 22162884
TI  - Decision analysis modeling and comparative effectiveness research.

PMID- 22162885
TI  - Obstructive sleep apnea and hypertension: how strong is the association?

PMID- 22162886
TI  - Pro: lung cancer in 2011: a time for optimism and investment in new approaches
      and technologies with a commitment to produce evidence-based data.

PMID- 22162887
TI  - Con: the case for expanded lung cancer research support.

PMID- 22162888
TI  - Idiopathic Cheyne-Stokes respiration in acute respiratory acidosis.

PMID- 22162889
TI  - Further appraisal of the evidence underlying performance measures for community
      acquired pneumonia.

PMID- 22162890
TI  - Acute pulmonary embolism and dysfunction of CD3+ CD8+ T cell immunity.

PMID- 22162891
TI  - Giant cell interstitial pneumonia: report of two cases with high titanium
      concentration in the lung.

PMID- 22162892
TI  - Severe hypoxemia and orthodeoxia following right pneumonectomy.

PMID- 22162893
TI  - Innate and adaptive immunity: the 2011 Nobel Prize in Physiology or Medicine.

PMID- 22162894
TI  - Multicomponent Synthesis of 2,3-Dihydrochromeno[4,3-d]pyrazolo[3,4-b]pyridine-1,6
      diones: A Novel Heterocyclic Scaffold with Antibacterial Activity.
AB  - A multicomponent reaction of 3-aminopyrazol-5-ones with substituted salicylic
      aldehydes and acetylacetic ester leading to the formation of novel 2,3
      dihydrochromeno[4,3-d]pyrazolo[3,4-b]pyridine-1,6-diones was discovered. The
      elucidation of the reaction scope revealed that 5-aminopyrazoles, 3-amino-1,2,4
      triazoles and 6-aminouracil could be used as the heterocyclic amine component.
      Selected heterocyclic products were found to possess notable antibacterial
      activities.

PMID- 22162895
TI  - Remote sensing of ambient particles in Delhi and its environs: estimation and
      validation.
AB  - Recent advances in atmospheric remote sensing offer a unique opportunity to
      compute indirect estimates of air quality, particularly for developing countries
      that lack adequate spatial-temporal coverage of air pollution monitoring. The
      present research establishes an empirical relationship between satellite-based
      aerosol optical depth (AOD) and ambient particulate matter (PM) in Delhi and its
      environs. The PM data come from two different sources. Firstly, a field campaign
      was conducted to monitor airborne particles <= 2.5 MUm and <=10 MUm in
      aerodynamic diameter (PM(2.5) and PM(10) respectively) at 113 spatially dispersed
      sites from July to December 2003 using photometric samplers. Secondly, data on
      eight hourly PM(10) and total suspended particulate (TSP) matter, collected using
      gravimetric samplers, from 2000 to 2005 were acquired from the Central Pollution
      Control Board (CPCB). The aerosol optical depths were estimated from MODIS data,
      acquired from NASA's Goddard Space Flight Center Earth Sciences Distributed
      Active Archive Center from 2000 to 2005. Both the PM and AOD data were collocated
      by time and space: PM mass +/- 150 min of AOD time, and +/- 2.5 and 5 km radius
      (separately) of the centroid of the AOD pixel for the 5 and 10 km AOD,
      respectively. The analysis here shows that PM correlates positively with the 5 km
      AOD; a 1% change in the AOD explains 0.52% +/- 0.20% and 0.39% +/- 0.15% changes
      in PM(2.5) within 45 and 150 min intervals (of AOD data) respectively. At a
      coarser spatial resolution, however, the relationship between AOD and PM is
      relatively weak. But, the relationship turns significantly stronger when monthly
      estimates are analysed over a span of six years (2000 to 2005), especially for
      the winter months, which have relatively stable meteorological conditions.

PMID- 22162896
TI  - Hard or Soft Classification? Large-margin Unified Machines.
AB  - Margin-based classifiers have been popular in both machine learning and
      statistics for classification problems. Among numerous classifiers, some are hard
      classifiers while some are soft ones. Soft classifiers explicitly estimate the
      class conditional probabilities and then perform classification based on
      estimated probabilities. In contrast, hard classifiers directly target on the
      classification decision boundary without producing the probability estimation.
      These two types of classifiers are based on different philosophies and each has
      its own merits. In this paper, we propose a novel family of large-margin
      classifiers, namely large-margin unified machines (LUMs), which covers a broad
      range of margin-based classifiers including both hard and soft ones. By offering
      a natural bridge from soft to hard classification, the LUM provides a unified
      algorithm to fit various classifiers and hence a convenient platform to compare
      hard and soft classification. Both theoretical consistency and numerical
      performance of LUMs are explored. Our numerical study sheds some light on the
      choice between hard and soft classifiers in various classification problems.

PMID- 22162897
TI  - Role of structural anisotropy of biological tissues in poroelastic wave
      propagation.
AB  - Ultrasound waves have a broad range of clinical applications as a non-destructive
      testing approach in imaging and in the diagnoses of medical conditions.
      Generally, biological tissues are modeled as an homogenized equivalent medium
      with an apparent density through which a single wave propagates. Only the first
      wave arriving at the ultrasound probe is used for the measurement of the speed of
      sound. However, the existence of a second wave in tissues such as cancellous bone
      has been reported and its existence is an unequivocal signature of Biot type
      poroelastic media. To account for the fact that ultrasound is sensitive to
      microarchitecture as well as density, a fabric-dependent anisotropic poroelastic
      ultrasound (PEU) propagation theory was recently developed. Key to this
      development was the inclusion of the fabric tensor - a quantitative stereological
      measure of the degree of structural anisotropy of bone - into the linear
      poroelasticity theory. In the present study, this framework is extended to the
      propagation of waves in several soft and hard tissues. It was found that collagen
      fibers in soft tissues and the mineralized matrix in hard tissues are responsible
      for the anisotropy of the solid tissue constituent through the fabric tensor in
      the model.

PMID- 22162898
TI  - Moral ape philosophy.
AB  - Our closest relative the chimpanzee seems to display proto-moral behavior. Some
      scholars emphasize the similarities between humans and chimpanzees, others some
      key differences. This paper aims is to formulate a set of intermediate conditions
      between a sometimes helpful chimpanzee and moral man. I specify these
      intermediate conditions as requirements for the chimpanzees, and for each
      requirement I take on a verificationist stance and ask what the empirical
      conditions that satisfy it would be. I ask what would plausibly count as the
      behavioral correlate of each requirement, when implemented. I take a
      philosophical look at morality using the chimpanzees as a prism. We will talk of
      propositional attitudes, rationality and reason in relation to the chimps. By
      means of the chimps I intend to arrive at a notion of objective morality as
      conceived from a first person point of view in terms of propositional attitudes
      and reasons.

PMID- 22162899
TI  - Duet function in the yellow-naped amazon, Amazona auropalliata: evidence from
      playbacks of duets and solos.
AB  - The question of why animals participate in duets is an intriguing one, as many
      such displays appear to be more costly to produce than individual signals. Mated
      pairs of yellow-naped amazons, Amazona auropalliata, give duets on their nesting
      territories. We investigated the function of those duets with a playback
      experiment. We tested two hypotheses for the function of those duets: the joint
      territory defense hypothesis and the mate-guarding hypothesis, by presenting
      territorial pairs with three types of playback treatments: duets, male solos, and
      female solos. The joint territory defense hypothesis suggests that individuals
      engage in duets because they appear more threatening than solos and are thus more
      effective for the establishment, maintenance and/or defense of territories. It
      predicts that pairs will be coordinated in their response (pair members approach
      speakers and vocalize together) and will either respond more strongly (more calls
      and/or more movement) to duet treatments than to solo treatments, or respond
      equally to all treatments. Alternatively, the mate-guarding hypothesis suggests
      that individuals participate in duets because they allow them to acoustically
      guard their mate, and predicts uncoordinated responses by pairs, with weak
      responses to duet treatments and stronger responses by individuals to solos
      produced by the same sex. Yellow-naped amazon pairs responded to all treatments
      in an equivalently aggressive and coordinated manner by rapidly approaching
      speakers and vocalizing more. These responses generally support the joint
      territory defense hypothesis and further suggest that all intruders are viewed as
      a threat by resident pairs.

PMID- 22162900
TI  - License Compliance Issues For Biopharmaceuticals: Special Challenges For
      Negotiations Between Companies And Non-Profit Research Institutions.
AB  - Biopharmaceuticals are therapeutic products based on biotechnology. They are
      manufactured by or from living organisms and are the most complex of all
      commercial medicines to develop, manufacture and qualify for regulatory approval.
      In recent years biopharmaceuticals have rapidly increased in number and
      importance with over 400() already marketed in the U.S. and European markets
      alone. Many companies throughout the world are now ramping up investments in
      biopharmaceutical R&D and expanding their portfolios through licensing of early
      stage biotechnologies from universities and other non-profit research
      institutions, and there is an increasing number of license agreements for
      biopharmaceutical product development relative to traditional small molecule drug
      compounds. This trend will only continue as large numbers of biosimilars and
      biogenerics enter the market.A primary goal of technology transfer offices
      associated with publicly-funded, non-profit research institutions is to establish
      patent protection for inventions deemed to have commercial potential and license
      them for product development. Such licenses help stimulate economic development
      and job creation, bring a stream of royalty revenue to the institution and,
      hopefully, advance the public good or public health by bringing new and useful
      products to market. In the course of applying for such licenses, a commercial
      development plan is usually put forth by the license applicant. This plan
      indicates the path the applicant expects to follow to bring the licensed
      invention to market. In the case of small molecule drug compounds, there exists a
      widely-recognized series of clinical development steps, dictated by regulatory
      requirements, that must be met to bring a new drug to market, such as completion
      of preclinical toxicology, Phase 1, 2 and 3 testing and product approvals. These
      steps often become the milestone/benchmark schedule incorporated into license
      agreements which technology transfer offices use to monitor the licensee's
      diligence and progress; most exclusive licenses include a commercial development
      plan, with penalties, financial or even revocation of the license, if the plan is
      not followed, e.g., the license falls too far behind.This study examines whether
      developmental milestone schedules based on a small molecule drug development
      model are useful and realistic in setting expectations for biopharmaceutical
      product development. We reviewed the monitoring records of all exclusive Public
      Health Service (PHS) commercial development license agreements for small molecule
      drugs or therapeutics based on biotechnology (biopharmaceuticals) executed by the
      National Institutes of Health (NIH) Office of Technology Transfer (OTT) between
      2003 and 2009. We found that most biopharmaceutical development license
      agreements required amending because developmental milestones in the negotiated
      schedule could not be met by the licensee. This was in stark contrast with
      license agreements for small molecule chemical compounds which rarely needed
      changes to their developmental milestone schedules. As commercial development
      licenses for biopharmaceuticals make up the vast majority of NIH's exclusive
      license agreements, there is clearly a need to: 1) more closely examine how these
      benchmark schedules are formed, 2) try to understand the particular risk factors
      contributing to benchmark schedule non-compliance, and 3) devise alternatives to
      the current license benchmark schedule structural model. Schedules that properly
      weigh the most relevant risk factors such as technology classification (e.g.,
      vaccine vs recombinant antibody vs gene therapy), likelihood of unforeseen
      regulatory issues, and company size/structure may help assure compliance with
      original license benchmark schedules. This understanding, coupled with a modified
      approach to the license negotiation process that makes use of a clear and
      comprehensive term sheet to minimize ambiguities should result in a more
      realistic benchmark schedule.

PMID- 22162901
TI  - Getting a Job is Only Half the Battle: Maternal Job Loss and Child Classroom
      Behavior in Low-Income Families.
AB  - This study uses data from an experimental employment program and instrumental
      variables (IV) estimation to examine the effects of maternal job loss on child
      classroom behavior. Random assignment to the treatment at one of three program
      sites is an exogenous predictor of employment patterns. Cross-site variation in
      treatment-control differences is used to identify the effects of employment
      levels and transitions. Under certain assumptions, this method controls for
      unobserved correlates of job loss and child well-being, as well as measurement
      error and simultaneity. IV estimates suggest that maternal job loss sharply
      increases problem behavior but has neutral effects on positive social behavior.
      Current employment programs concentrate primarily on job entry, but these
      findings point to the importance of promoting job stability for workers and their
      children.

PMID- 22162902
TI  - Robust penalized logistic regression with truncated loss functions.
AB  - The penalized logistic regression (PLR) is a powerful statistical tool for
      classification. It has been commonly used in many practical problems. Despite its
      success, since the loss function of the PLR is unbounded, resulting classifiers
      can be sensitive to outliers. To build more robust classifiers, we propose the
      robust PLR (RPLR) which uses truncated logistic loss functions, and suggest three
      schemes to estimate conditional class probabilities. Connections of the RPLR with
      some other existing work on robust logistic regression have been discussed. Our
      theoretical results indicate that the RPLR is Fisher consistent and more robust
      to outliers. Moreover, we develop estimated generalized approximate cross
      validation (EGACV) for the tuning parameter selection. Through numerical
      examples, we demonstrate that truncating the loss function indeed yields better
      performance in terms of classification accuracy and class probability estimation.

PMID- 22162903
TI  - Territory choice during the breeding tenure of male sedge warblers.
AB  - A territorial male can shift the location of its territory from year to year in
      order to increase its quality. The male can base its decision on environmental
      cues or else on its breeding experiences (when territory shift is caused by
      breeding failure in previous seasons). We tested these possible mechanisms of
      territory choice in the sedge warbler (Acrocephalus schoenobaenus), a territorial
      migrating passerine that occupies wetlands. This species bases its territory
      choices on an environmental cue: tall wetland vegetation cover. We found that the
      magnitude of territory quality improvement between seasons (measured as the area
      of tall wetland vegetation) increased throughout the early stages of a male's
      breeding career as a result of territory shifts dependent on the earliness of
      arrival. The distance the territory was shifted between seasons depended
      negatively on the previous year's territory quality and, less clearly, on the
      previous year's mating success. On the other hand, previous mating or nesting
      success had no influence on territory quality improvement between seasons as
      measured in terms of vegetation. The results imply that tall wetland vegetation
      is a long-term, effective environmental cue and that a preference for territories
      in which this type of landcover prevails has evolved into a rigid behavioral
      mechanism, supplemented by short-term individual experiences of breeding failure.

PMID- 22162904
TI  - Understanding and producing the reduced relative construction: Evidence from
      ratings, editing and corpora.
AB  - Tworating studies demonstrate that English speakers willingly produce reduced
      relatives with internal cause verbs (e.g., Whisky fermented in oak barrels can
      have a woody taste), and judge their acceptability based on factors known to
      influence ambiguity resolution, rather than on the internal/external cause
      distinction. Regression analyses demonstrate that frequency of passive usage
      predicts reduced relative frequency in corpora, but internal/external cause
      status does not. The authors conclude that reduced relatives with internal cause
      verbs are rare because few of these verbs occur in the passive. This contrasts
      with the claim in McKoon and Ratcliff (McKoon, G., & Ratcliff, R. (2003). Meaning
      through syntax: Language comprehension and the reduced relative clause
      construction. Psychological Review, 110, 490-525) that reduced relatives like The
      horse raced past the barn fell are rare and, when they occur, incomprehensible,
      because the meaning of the reduced relative construction prohibits the use of a
      verb with an internal cause event template.

PMID- 22162905
TI  - Long-term exposure of chemokine CXCL10 causes bronchiolitis-like inflammation.
AB  - Chemokines and chemokine receptors have been implicated in the pathogenesis of
      bronchiolitis. CXCR3 ligands (CXCL10, CXCL9, and CXCL11) were elevated in
      patients with bronchiolitis obliterans syndrome (BOS) and chronic allorejection.
      Studies also suggested that blockage of CXCR3 or its ligands changed the outcome
      of T-cell recruitment and airway obliteration. We wanted to determine the role of
      the chemokine CXCL10 in the pathogenesis of bronchiolitis and BOS. In this study,
      we found that CXCL10 mRNA levels were significantly increased in patients with
      BOS. We generated transgenic mice expressing a mouse CXCL10 cDNA under control of
      the rat CC10 promoter. Six-month-old CC10-CXCL10 transgenic mice developed
      bronchiolitis characterized by airway epithelial hyperplasia and developed
      peribronchiolar and perivascular lymphocyte infiltration. The airway hyperplasia
      and T-cell inflammation were dependent on the presence of CXCR3. Therefore, long
      term exposure of the chemokine CXCL10 in the lung causes bronchiolitis-like
      inflammation in mice.

PMID- 22162907
TI  - Albuterol modulates its own transepithelial flux via changes in paracellular
      permeability.
AB  - Although inhaled bronchodilators are commonly used in the treatment of airway
      disease to dilate airway smooth muscle, little is known regarding the mechanisms
      that regulate albuterol movement across the epithelium to reach its target, the
      airway smooth muscle. Because the rate of onset depends on the transepithelial
      transport of albuterol, to determine the mechanisms that regulate the
      transepithelial movement of albuterol is essential. Human bronchial epithelial
      cells, fully redifferentiated in culture at the air-liquid interface, were used
      to study the cellular uptake and total transepithelial flux of (3)H-albuterol
      from the apical to the basolateral surfaces. (3)H-mannitol and transepithelial
      electrical resistance were used to quantify changes in paracellular permeability.
      The majority of albuterol flux across the epithelium occurred via the
      paracellular route. The cellular uptake of albuterol was found to be saturable,
      whereas transepithelial flux was not. Cellular uptake could be inhibited by the
      amino acids lysine and histidine, with no effect on net transepithelial flux.
      Transepithelial flux was altered by maneuvers that collapsed or disrupted
      intercellular junctions. Acidification, usually seen in exacerbations of airway
      disease, decreased albuterol flux. In addition, albuterol increased its own
      paracellular permeability. The ability of albuterol to modulate paracellular
      permeability was blocked by the beta(2)-adrenergic receptor-selective antagonist
      ICI 118551. Albuterol mainly crosses the epithelium via the paracellular pathway,
      but has the ability to modulate its own permeability through changes in the
      leakiness of tight junctions, which is modulated through the signaling of the
      beta(2)-adrenergic receptor.

PMID- 22162906
TI  - Post-exposure antioxidant treatment in rats decreases airway hyperplasia and
      hyperreactivity due to chlorine inhalation.
AB  - We assessed the safety and efficacy of combined intravenous and aerosolized
      antioxidant administration to attenuate chlorine gas-induced airway alterations
      when administered after exposure. Adult male Sprague-Dawley rats were exposed to
      air or 400 parts per million (ppm) chlorine (a concentration likely to be
      encountered in the vicinity of industrial accidents) in environmental chambers
      for 30 minutes, and returned to room air, and they then received a single
      intravenous injection of ascorbic acid and deferoxamine or saline. At 1 hour and
      15 hours after chlorine exposure, the rats were treated with aerosolized
      ascorbate and deferoxamine or vehicle. Lung antioxidant profiles, plasma
      ascorbate concentrations, airway morphology, and airway reactivity were evaluated
      at 24 hours and 7 days after chlorine exposure. At 24 hours after exposure,
      chlorine-exposed rats had significantly lower pulmonary ascorbate and reduced
      glutathione concentrations. Treatment with antioxidants restored depleted
      ascorbate in lungs and plasma. At 7 days after exposure, in chlorine-exposed,
      vehicle-treated rats, the thickness of the proximal airways was 60% greater than
      in control rats, with twice the amount of mucosubstances. Airway resistance in
      response to methacholine challenge was also significantly elevated. Combined
      treatment with intravenous and aerosolized antioxidants restored airway
      morphology, the amount of airway mucosubstances, and airway reactivity to control
      levels by 7 days after chlorine exposure. Our results demonstrate for the first
      time, to the best of our knowledge, that severe injury to major airways in rats
      exposed to chlorine, as characterized by epithelial hyperplasia, mucus
      accumulation, and airway hyperreactivity, can be reversed in a safe and
      efficacious manner by the post-exposure administration of ascorbate and
      deferoxamine.

PMID- 22162908
TI  - alpha1-antitrypsin production by proinflammatory and antiinflammatory macrophages
      and dendritic cells.
AB  - alpha(1)-Antitrypsin (AAT) acts as an important neutrophil elastase inhibitor in
      the lung. Although the hepatocyte is considered to be the primary source of AAT,
      local production by monocytes, macrophages, and epithelial cells may contribute
      to the formation of an antielastase screen. Because monocytes can differentiate
      into a heterogeneous population of macrophages with subpopulations ranging from
      proinflammatory properties (MPhi-1) to antiinflammatory properties (MUPhi-2) and
      into dendritic cells (DCs), we studied whether LPS, TNF-alpha, and oncostatin M
      (OSM) enhance AAT production differentially in cultured MUPhi-1, MUPhi-2, and
      DCs. Monocytes from healthy blood donors were cultured for 7 days in the presence
      of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony
      stimulating factor, or GM-CSF with IL-4 to obtain MUPhi-1, MUPhi-2, and immature
      (i)DCs, respectively. Cells were stimulated with LPS, TNF-alpha, or OSM, and AAT
      synthesis was assessed by quantitative RT-PCR, immunocytochemistry, and ELISA.
      Spontaneous release of AAT was higher in MUPhi-1 than in MUPhi-2 and iDCs, and
      only LPS significantly increased AAT production in MUPhi-1, MUPhi-2, and DC. TNF
      alpha and OSM did not affect AAT secretion. The secretion levels of the related
      protease inhibitors alpha-1 antichymotrypsin and secretory leukocyte proteinase
      inhibitor were below the limits of detection by ELISA. In contrast to the protein
      data, analysis by quantitative RT-PCR showed that 24-hour LPS exposure caused a
      maximal 2.1-fold AAT mRNA increase in MUPhi-1, a 21-fold increase in MUPhi-2, and
      an 11-fold increase in DCs. These data suggest that cellular differentiation is a
      regulator of local AAT production.

PMID- 22162909
TI  - Copper dependence of angioproliferation in pulmonary arterial hypertension in
      rats and humans.
AB  - Obliteration of the vascular lumen by endothelial cell growth is a hallmark of
      many forms of severe pulmonary arterial hypertension. Copper plays a significant
      role in the control of endothelial cell proliferation in cancer and wound
      healing. We sought to determine whether angioproliferation in rats with
      experimental pulmonary arterial hypertension and pulmonary microvascular
      endothelial cell proliferation in humans depend on the proangiogenic action of
      copper. A copper-depleted diet prevented, and copper chelation with
      tetrathiomolybdate reversed, the development of severe experimental pulmonary
      arterial hypertension. The copper chelation-induced reopening of obliterated
      vessels was caused by caspase-independent apoptosis, reduced vessel wall cell
      proliferation, and a normalization of vessel wall structure. No evidence was
      found for a role of super oxide-1 inhibition or lysyl-oxidase-1 inhibition in the
      reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of
      human pulmonary microvascular endothelial cells, isolated from explanted lungs
      from control subjects and patients with pulmonary arterial hypertension. These
      data suggest that the inhibition of endothelial cell proliferation by a copper
      restricting strategy could be explored as a new therapeutic approach in pulmonary
      arterial hypertension. It remains to be determined, however, whether potential
      toxicity to the right ventricle is offset by the beneficial pulmonary vascular
      effects of antiangiogenic treatment in patients with pulmonary arterial
      hypertension.

PMID- 22162910
TI  - Treatment of post-traumatic degenerative changes of the radio-carpal and distal
      radio-ulnar joints by combining radius, scaphoid, and lunate (RSL) fusion with
      ulnar head replacement.
AB  - Distal radial fractures are a common type of fracture. In the case of intra
      articular fractures, they often result in post-traumatic arthrosis. The objective
      of this study is to describe a novel alternative to the established salvage
      techniques for the treatment of post-traumatic arthrosis of the radio-carpal and
      distal radio-ulnar joints (DRUJ). Six patients with radio-carpal and DRUJ
      arthrosis were treated with a combined radius, scaphoid, and lunate (RSL)
      arthrodesis and as a Herbert ulnar head prosthesis. Follow-up consisted of both
      radiographic and functional assessments. Functional measurements were noted both
      pre- and postoperatively. No non-union or pseudoarthrosis was seen; neither did
      any of the ulnar head prostheses show loosening. Clinical examination showed an
      improvement in strength, pain, and range of movement, as well as a decrease in
      disability. Combining RSL arthrodesis with a Herbert ulnar head prosthesis, which
      deals with pain while retaining partial wrist movement, can be an alternative to
      established salvage procedures.

PMID- 22162911
TI  - Deep sternal wound infection after open heart surgery: current treatment
      insights. A retrospective study of 36 cases.
AB  - The aim of this study was to retrospectively evaluate the results of
      reconstructing infected post-sternotomy wounds, with either sternal plating
      and/or pectoralis major flap transposition or pedicled omentoplasty after
      previous vacuum-assisted closure (VAC) therapy. Between January 2005 and December
      2010, 36 patients, suffering from deep sternal wound infection (DSWI) after
      coronary artery bypass grafting procedure, received (plastic) reconstructive
      surgery. All patients, treated in the Maastricht University Medical Centre
      (Departments of Plastic Surgery and Cardiothoracic Surgery), were selected for
      this study. For 22 patients, sternal refixation and reconstruction were obtained
      by sternal internal plate fixation combined with bilateral pectoralis major
      advancement flap. In 11 patients, a pedicled omentoplasty was performed, with or
      without split-skin graft and additional VAC therapy. Three patients only received
      a pectoralis plasty. We evaluated preoperative characteristics and post-operative
      course. Twenty-four patients (66.7%) had an uneventful post-operative course.
      Complications in the other patients included wound dehiscence, herniation of the
      donor site and infection of sternal plating material. Average sternal wound
      healing after sternal plating plus pectoralis plasty, pectoralis plasty and
      omentoplasty respectively accounted 7.7, 8.0 and 11.6 weeks. From our experience,
      we recommend VAC therapy plus delayed sternal plating and additional bilateral
      pectoralis major flap advancement as first repair option in case of DSWI.
      However, individual clinical conditions need to be taken into account when making
      a decision between the different available reconstructive options. Omentoplasty
      should be reserved for cases in which the sternum has recurrently fallen open
      after previous sternal plate refixation, or for cases in which the sternum defect
      is too extended.

PMID- 22162912
TI  - EPR and Quantum Chemical Studies of the pH-sensitive Imidazoline and
      Imidazolidine Nitroxides with Bulky Substituents.
AB  - The X- and W-band electron paramagnetic resonance (EPR) spectroscopies were
      employed to investigate a series of imidazolidine nitroxide radicals with
      different number of ethyl and methyl substituents at positions 2 and 5 of a
      heterocycle in liquid and frozen solutions. The influence of the substituents on
      the line shape and width was studied experimentally and analyzed using quantum
      chemical calculations. Each pair of the geminal ethyl groups in the positions 2
      or 5 of the imidazolidine ring was found to produce an additional hyperfine
      splitting (hfs) of about 0.2 mT in the EPR spectra of the nitroxides. The effect
      was attributed to the hfs constant of only one of four methylene hydrogen atoms
      of two geminal ethyl substituents not fully averaged by ethyl group rotation and
      ring puckering. In accordance with this assumption, the substitution of hydrogen
      atoms of CH(2) groups in 2,2,5,5-tetraethyl-substituted imidazolidine nitroxides
      by deuterium leads to the substantial narrowing of EPR lines which could be
      useful for many biochemical and biomedical applications, including pH-monitoring.
      W-band EPR spectra of 2,2,5,5-tetraethyl-substituted imidazolidine nitroxide and
      its 2,2,5,5-tetraethyl-d(8) deuterium-substituted analog measured at low
      temperatures demonstrated high sensitivity of their g-factors to pH, which
      indicates their applicability as spin labels possessing high stability.

PMID- 22162913
TI  - A Tribute to Renad Z. Sagdeev on the Occasion of His 70th Birthday.

PMID- 22162914
TI  - Current CONtrolled Transmit And Receive Coil Elements (CONTAR) for Parallel
      Acquisition and Parallel Excitation Techniques at High-Field MRI.
AB  - A novel intrinsically decoupled transmit and receive radio-frequency coil element
      is presented for applications in parallel imaging and parallel excitation
      techniques in high-field magnetic resonance imaging. Decoupling is achieved by a
      twofold strategy: during transmission elements are driven by current sources,
      while during signal reception resonant elements are switched to a high input
      impedance preamplifier. To avoid B(0) distortions by magnetic impurities or DC
      currents a resonant transmission line is used to relocate electronic components
      from the vicinity of the imaged object. The performance of a four-element array
      for 3 T magnetic resonance tomograph is analyzed by means of simulation,
      measurements of electromagnetic fields and bench experiments. The feasibility of
      parallel acquisition and parallel excitation is demonstrated and compared to that
      of a conventional power source-driven array of equivalent geometry. Due to their
      intrinsic decoupling the current-controlled elements are ideal basic building
      blocks for multi-element transmit and receive arrays of flexible geometry.

PMID- 22162915
TI  - The Influence of Look-Ahead on the Error Rate of Transcription.
AB  - In this paper we study the error rate of RNA synthesis in the look-ahead model
      for the random walk of RNA polymerase along DNA during transcription. The model's
      central assumption is the existence of a window of activity in which
      ribonucleoside triphosphates (rNTPs) bind reversibly to the template DNA strand
      before being hydrolyzed and linked covalently to the nascent RNA chain. An
      unknown, but important, integer parameter of this model is the window size w.
      Here, we use mathematical analysis and computer simulation to study the rate at
      which transcriptional errors occur as a function of w. We find dramatic reduction
      in the error rate of transcription as w increases, especially for small values of
      w. The error reduction method provided by look-ahead occurs before hydrolysis and
      covalent linkage of rNTP to the nascent RNA chain, and is therefore distinct from
      error correction mechanisms that have previously been considered.

PMID- 22162916
TI  - In vitro near-infrared imaging of occlusal dental caries using germanium enhanced
      CMOS camera.
AB  - The high transparency of dental enamel in the near-infrared (NIR) at 1310-nm can
      be exploited for imaging dental caries without the use of ionizing radiation. The
      objective of this study was to determine whether the lesion contrast derived from
      NIR transillumination can be used to estimate lesion severity. Another aim was to
      compare the performance of a new Ge enhanced complementary metal-oxide
      semiconductor (CMOS) based NIR imaging camera with the InGaAs focal plane array
      (FPA). Extracted human teeth (n=52) with natural occlusal caries were imaged with
      both cameras at 1310-nm and the image contrast between sound and carious regions
      was calculated. After NIR imaging, teeth were sectioned and examined using more
      established methods, namely polarized light microscopy (PLM) and transverse
      microradiography (TMR) to calculate lesion severity. Lesions were then classified
      into 4 categories according to the lesion severity. Lesion contrast increased
      significantly with lesion severity for both cameras (p<0.05). The Ge enhanced
      CMOS camera equipped with the larger array and smaller pixels yielded higher
      contrast values compared with the smaller InGaAs FPA (p<0.01). Results
      demonstrate that NIR lesion contrast can be used to estimate lesion severity.

PMID- 22162917
TI  - Workplace alcohol testing program by combined use of ethyl glucuronide and fatty
      acid ethyl esters in hair.
AB  - AIMS: The applicability of fatty acid ethyl esters (FAEEs) and ethyl glucuronide
      (EtG) in hair in a workplace alcohol testing program was investigated. METHODS: A
      total of 78 hair samples from employees in jobs with a high endangering potential
      were tested for EtG and FAEEs. In most cases excessive drinking was suspected.
      For 59 of these cases additional data of the traditional alcohol markers
      aspartate aminotransferase, alanine aminotransferase and gamma
      glutamyltransferase and of the mean corpuscular volume of the erythrocytes (58
      cases) were available. RESULTS: By application of the cut-offs of the Consensus
      of the Society of Hair Testing and of a gradual system for combined
      interpretation of FAEEs and EtG in hair no indications of alcohol abuse were
      obtained in 50 cases (64%), slight indications were seen in 13 cases (17%) and
      clear indications in 11 cases (14%). In four cases, the results were inconclusive
      with strongly conflicting results of both markers, the reason for which could not
      be cleared. The traditional markers confirmed the hair results only partly and
      displayed altogether a lower portion of positive results. CONCLUSION: EtG and
      FAEEs in hair, especially when interpreted in combination, are suitable for
      application in workplace alcohol testing programs. Nevertheless, the results
      obtained by hair analysis for alcohol markers can only be one part of a proper
      assessment aiming at the question whether an employee is addicted to alcohol or
      not.

PMID- 22162918
TI  - Accounting for network effects in neuronal responses using L1 regularized point
      process models.
AB  - Activity of a neuron, even in the early sensory areas, is not simply a function
      of its local receptive field or tuning properties, but depends on global context
      of the stimulus, as well as the neural context. This suggests the activity of the
      surrounding neurons and global brain states can exert considerable influence on
      the activity of a neuron. In this paper we implemented an L1 regularized point
      process model to assess the contribution of multiple factors to the firing rate
      of many individual units recorded simultaneously from V1 with a 96-electrode
      "Utah" array. We found that the spikes of surrounding neurons indeed provide
      strong predictions of a neuron's response, in addition to the neuron's receptive
      field transfer function. We also found that the same spikes could be accounted
      for with the local field potentials, a surrogate measure of global network
      states. This work shows that accounting for network fluctuations can improve
      estimates of single trial firing rate and stimulus-response transfer functions.

PMID- 22162919
TI  - Role of iron supplementation in promoting maternal and fetal outcome.
AB  - BACKGROUND: The data comparing daily versus intermittent iron supplementation
      during pregnancy remain controversial. This study was undertaken to compare the
      efficacy of daily versus two different intermittent iron supplementation regimes
      on hematologic markers and birth outcomes in nonanemic pregnant women. METHODS:
      Two hundred and ten women with singleton pregnancies, no known disease, and
      hemoglobin levels >11.0 g/dL were randomly assigned to one of three groups, ie,
      Group A consuming two iron supplementation tablets once weekly (100 mg iron per
      week, n = 70), Group B consuming one tablet twice weekly (100 mg iron per week, n
      = 70) and Group C, consuming one tablet daily (50 mg iron per day, n = 70). No
      additional micronutrients were supplied. Hemoglobin and serum ferritin levels
      were measured at 20, 28, and 38 weeks. Pregnancy and birth outcomes (pregnancy
      termination, method of delivery, birth weight, stillbirth) were analyzed.
      RESULTS: In total, 201 women completed the protocol. There was a significant
      difference in mean hemoglobin and ferritin levels in Group B at 38 weeks (P =
      0.018 and P = 0.035, respectively) but this difference was not clinically
      significant (hemoglobin >12 g/dL, ferritin >19 MUg/L). There was a significant
      increase in ferritin in Group C (P = 0.03) at 28 weeks. No significant difference
      was observed with respect to pregnancy or birth outcome across the groups. All
      regimens prevented the occurrence of hemoglobin <10.5 g/dL, but weekly
      supplementation was associated with development of a hemoglobin level <11.0 g/dL
      (risk ratio 0.044). CONCLUSION: Twice-weekly supplementation is as effective as
      daily supplementation, and may represent an acceptable compromise in iron
      supplementation regimens for nonanemic pregnant women.

PMID- 22162920
TI  - Correlation between lamivudine plasma concentrations and patient self-reported
      adherence to antiretroviral treatment in experienced HIV patients.
AB  - BACKGROUND: Adherence to antiretroviral treatment (ART) is important to achieve
      treatment success in human immunodeficiency virus (HIV)-infected patients. Most
      HIV clinics apply the patient self-report (PSR) method. However, the reliability
      of this method in experienced HIV patients remains questionable. PURPOSE: To
      validate the PSR method for measuring adherence to ART using lamivudine (3TC)
      plasma concentrations in experienced HIV patients. METHODS: The study was
      conducted in Dar Es Salaam and involved 220 patients who were receiving ART
      services at HIV clinics for more than 12 months. Self-reported adherence
      information to ART was obtained on the day of HIV clinic visit. The patients were
      asked to mention the number of doses missed within the past 7 days. In addition,
      blood samples (2 mL) were collected from each patient on the same day. The blood
      samples were determined for 3TC plasma concentrations. The target 3TC plasma
      concentration as indicator concentration for adherent patients was determined in
      20 patients who took their evening dose of antiretrovirals under supervision. The
      blood from these patients was drawn 3 hours after drug administration. RESULTS:
      Complete drug levels of 3TC and self-reported adherence data was obtained in 200
      treatment-experienced HIV patients. Lamivudine plasma concentrations obtained in
      these patients ranged between 0.02-17.36 MUg/mL. The mean time from dose
      administration to blood drawing was 3.1 +/- 1.2 hours with coefficient of
      variation >39%. The mean 3TC plasma concentration obtained in 20 patients who
      took their antiretroviral dose under supervision was found to be 0.67 +/- 0.46
      MUg/mL, range 0.25-2.33 MUg/mL. As many as 82.5% of experienced HIV patients had
      PSRs in agreement with their 3TC plasma concentrations. CONCLUSION: PSR adherence
      is still a valid method for ascertaining adherence to ART in treatment
      experienced HIV patients.

PMID- 22162921
TI  - Optimal management of Barrett's esophagus: pharmacologic, endoscopic, and
      surgical interventions.
AB  - Esophageal adenocarcinoma and its precursor, Barrett's esophagus, are rapidly
      rising in incidence. This review serves to highlight the role of pharmacologic,
      endoscopic, and surgical intervention in the management of Barrett's esophagus,
      which requires acid suppression and endoscopic assessment. Treatment with a
      proton pump inhibitor may decrease acid exposure and delay the progression to
      dysplasia. Patients who require aspirin for cardioprotection or other indications
      may also benefit in terms of a protective effect against the development of
      esophageal cancer. However, without other indications, aspirin is not indicated
      solely to prevent cancer. A careful endoscopic examination should include
      assessment of any visible lesions in a Barrett's segment. An expert
      gastrointestinal pathologist should confirm neoplasia in the setting of Barrett's
      esophagus. For those patients with high-grade dysplasia or intramucosal
      carcinoma, careful consideration of endoscopic therapy or surgical therapy must
      be given. All visible lesions in the setting of dysplasia should be targeted with
      focal endoscopic mucosal resection for both accurate histopathologic diagnosis
      and treatment. The remainder of the Barrett's epithelium should be eradicated to
      address all synchronous and metachronous lesions. This may be done by tissue
      acquiring or nontissue acquiring means. Radiofrequency ablation has a positive
      benefit-risk profile for flat Barrett's esophagus. At this time, endoscopic
      therapy is not indicated for nondysplastic Barrett's esophagus. Esophagectomy is
      still reserved for selected cases with evidence of lymph node metastasis,
      unsuccessful endoscopic therapy, or with high-risk features of high-grade
      dysplasia or intramucosal carcinoma.

PMID- 22162922
TI  - Zofenopril and incidence of cough: a review of published and unpublished data.
AB  - OBJECTIVE: Cough is a typical side effect of angiotensin-converting enzyme (ACE)
      inhibitors, though its frequency quantitatively varies among the different
      compounds. Data on the incidence of cough with the lipophilic third-generation
      ACE inhibitor zofenopril are scanty and never systematically analyzed. The
      purpose of this paper is to give an overview on the epidemiology,
      pathophysiology, and treatment of ACE inhibitor-induced cough and to assess the
      incidence of cough induced by zofenopril treatment. METHODS: Published and
      unpublished data from randomized and postmarketing zofenopril trials were merged
      together and analyzed. RESULTS: Twenty-three studies including 5794 hypertensive
      patients and three studies including 1455 postmyocardial infarction patients
      exposed for a median follow-up time of 3 months to zofenopril at doses of 7.5-60
      mg once-daily were analyzed. The incidence of zofenopril-induced cough was 2.6%
      (range 0%-4.2%): 2.4% in the hypertension trials (2.4% in the double-blind
      randomized studies and 2.4% in the open-label postmarketing studies) and 3.6% in
      the doubleblind randomized postmyocardial infarction trials. Zofenopril-induced
      cough was generally of a mild to moderate intensity, occurred significantly (P <
      0.001) more frequently in the first 3-6 months of treatment (3.0% vs 0.2% 9-12
      months), and always resolved or improved upon therapy discontinuation. Zofenopril
      doses of 30 mg and 60 mg resulted in significantly (P = 0.042) greater rate of
      cough (2.1% and 2.6%, respectively) than doses of 7.5 mg and 15 mg (0.4% and
      0.7%, respectively). In direct comparison trials (enalapril and lisinopril),
      incidence of cough was not significantly different between zofenopril and other
      ACE inhibitors (2.4% vs 2.7%). CONCLUSION: Evidence from a limited number of
      studies indicates a relatively low incidence of zofenopril-induced cough. Large
      head-to-head comparison studies versus different ACE inhibitors are needed to
      highlight possible differences between zofenopril and other ACE inhibitors in the
      incidence of cough.

PMID- 22162923
TI  - Targeted treatment for chronic lymphocytic leukemia.
AB  - The treatment of chronic lymphocytic leukemia (CLL) has evolved over the last few
      decades. Recognition has increased of several key components of CLL biology
      currently manipulated for therapeutics. A milestone in the treatment of CLL was
      reached with the incorporation of immunotherapy with conventional chemotherapy.
      The fludarabine/cyclophosphamide/rituximab combination has demonstrated survival
      advantage for the first time in the treatment of CLL. Several other biological
      compounds are being explored with the hope of improving responses, impacting
      survival, and ultimately curing CLL. Important agents being tested are targeted
      on CLL surface molecules and their ligands, signal transduction protein and
      oncogenes. This review provides a brief summary of the recent advances made in
      preclinical and clinical investigation of selected promising therapeutic agents,
      which lead the target-directed therapeutic approach.

PMID- 22162925
TI  - Tegafur/gimeracil/oteracil (S-1) approved for the treatment of advanced gastric
      cancer in adults when given in combination with cisplatin: a review comparing it
      with other fluoropyrimidine-based therapies.
AB  - S-1 is a combination of three pharmacological compounds, namely tegafur,
      gimeracil, and oteracil potassium. Tegafur is a prodrug of 5-fluorouracil (5-FU),
      an oral fluoropyrimidine, and it has been developed as a replacement for
      infusional 5-FU therapy. S-1-based chemotherapy and the combination of S-1 and
      cisplatin are the most reasonable first-line standards for unresectable advanced
      gastric cancer in Japan. However, the application of S-1 for gastric cancer has
      been delayed in Western countries. One reason for this delay is that the
      pharmacokinetics of tegafur is affected by polymorphisms in cytochrome P-450 2A6,
      and consequently 5-FU concentrations in the plasma are more likely to be elevated
      in patients from Western countries. Although the dose of S-1 was reduced compared
      with the approved dose in Japan, a global Phase III study reported similar
      results regarding overall survival between S-1 plus cisplatin and infusional 5-FU
      plus cisplatin arms. Significant safety advantages were observed in the S-1 plus
      cisplatin arm compared with the infusional 5-FU plus cisplatin arm. S-1 plus
      cisplatin has become acceptable for Western countries, also, as a choice for
      unresectable advanced gastric cancer. Comparisons with capecitabine and
      combination of several targeting agents with S-1 are expected in the future.

PMID- 22162924
TI  - Eribulin mesylate as a microtubule inhibitor for treatment of patients with
      metastatic breast cancer.
AB  - Metastatic breast cancer (MBC) remains an incurable disease, with the goals of
      care aimed at maximizing the patient's duration and quality of life. Treatment
      options for MBC have become more efficacious and numerous. In addition to
      endocrine and chemotherapy agents, a number of targeted agents, including
      trastuzumab and bevacizumab, have further enhanced the landscape of therapeutic
      options. Eribulin mesylate (E7389) is a nontaxane microtubule dynamics inhibitor,
      and a structurally simplified synthetic analog of the natural marine product,
      halichondrin B, with a novel mechanism of action that has shown antitumor
      activity in pretreated MBC. Eribulin has shown a manageable tolerability profile
      in Phase I-II clinical trials and an improvement in overall survival compared
      with treatment of physician's choice, without relevant toxicities in a recently
      published Phase III trial. This review will focus on eribulin as a new active
      agent for MBC and its role in the management of breast disease.

PMID- 22162926
TI  - Surgical management of retrorectal tumors: a retrospective study of a 9-year
      experience in a single institution.
AB  - BACKGROUND: The relative rarity and anatomical position of retrorectal tumors may
      lead to difficulty in diagnosis and surgical management. METHODS: This was a
      retrospective review of 62 patients who had resection of retrorectal tumors
      between 2002 and 2010. RESULTS: All patients in this study were treated by
      excision of the retrorectal tumors. Surgical approach included transsacral
      approach (52 cases), transabdominal approach (eight cases), and combined approach
      (two cases). A total of 48 benign lesions (77.4%) and 14 malignant lesions
      (22.6%) were confirmed by histological examination. The 48 benign cases included
      dermoid cysts (17 cases), simple cysts (eight cases), teratomas (eight cases),
      neurofibromas (eight cases), fibrolipomas (four cases), neurilemmomas (two
      cases), and synovioma (one case). The 14 malignant cases included lymphomas (four
      cases), malignant teratomas (three cases), fibrosarcomas (two cases),
      interstitialomas (four cases) and malignant mesothelioma (one case).
      Complications occurred in 14.5% of patients and included intraoperative bleeding
      (three cases), rectal injury (three cases), and presacral infection (three
      cases). CONCLUSION: Primary retrorectal tumors are very rare. Successful
      treatment of these tumors requires extensive knowledge of pelvic anatomy and
      expertise in pelvic surgery.

PMID- 22162928
TI  - Erratum: corrigendum.
AB  - [This corrects the article on p. 213 in vol. 4, PMID: 22016582.].

PMID- 22162929
TI  - Adiposity factors are not related to the presence of colorectal adenomas.
AB  - PURPOSE: Adiposity has been thought to be related to colorectal carcinogenesis.
      The aim of this study was to explore any association between obesity factors and
      the presence of colorectal adenoma, a potential precancerous lesion. PATIENTS AND
      METHODS: Two hundred and six consecutive patients undergoing colonoscopy without
      colorectal cancer were enrolled in the study. Anthropometric measures and other
      adiposity-related laboratory variables including insulin resistance and serum
      adiponectin levels were recorded and correlated with the presence of adenoma.
      RESULTS: Colorectal adenoma was detected in 68/206 patients (33%), tubular
      adenoma(s) in 38 patients, and tubulovillous or villous in 30 patients. Twenty
      one patients (10.2%) had at least one proximal polyp. The size of the largest
      adenoma was <=10 mm in 40 patients and >10 mm in 28 patients. No statistically
      significant difference was observed in body mass index, waist circumference,
      fasting plasma glucose concentration, insulin, homeostatic metabolic assessment,
      cholesterol, low-density lipoproteins, high-density lipoprotein, or triglycerides
      between patients with and without adenoma. In addition, there was no difference
      in plasma adiponectin between patients with adenoma (11.1 +/- 6 MUg/mL) and
      controls (10.2 +/- 7.8 MUg/mL). Furthermore, no significant difference in any
      parameter was found between patients with advanced adenoma and no advanced
      adenoma, nor between patients with proximal or distal tumors. CONCLUSION: This
      study found that the presence of colorectal adenoma is not correlated with any
      adiposity factor. Moreover, obesity does not appear to be associated with the
      site or the presence of more advanced lesions.

PMID- 22162930
TI  - Gaps in continuity of care at the interface between primary care and specialized
      care: general practitioners' experiences and expectations.
AB  - INTRODUCTION: Discontinuity of care at the interface between inpatient and
      outpatient management can lead to increased morbidity and mortality. Appropriate
      communication and flow of information is indispensable to ensure continuity of
      care. Consequently, the aim of this study was to assess general practitioners'
      (GPs) experiences of cooperation with a university hospital, as well as their
      needs and obvious barriers regarding an optimized information flow. METHODS: A
      qualitative study was performed. In March 2011, 300 GPs from the Zurich Canton
      were invited to participate in two focus group meetings. Based on a review of the
      literature, an interview guide was created addressing two main issues. In the
      first part, experiences and barriers regarding cooperation with the university
      were explored. In the second part, needs and suggestions to improve cooperation
      were addressed. RESULTS: Fifteen GPs participated in two focus groups. GPs
      complained that they have often not been adequately informed about ongoing
      treatments or appointments for their patients. GPs feel responsible for the
      continuity of care and wish to be more involved, especially in long-term
      treatment decisions or at the end of life. By not involving them, they stated,
      important information concerning patients' medical history and social setting was
      not taken into account. Improvements are also required at discharge: GPs often do
      not receive important information about treatments in the hospital and further
      requirements within a reasonable time. CONCLUSION: Exchange of information
      between the hospital and the GP at admission and discharge is essential. However,
      at present, involvement during hospitalization of the patient is lacking. This
      includes the exchange of information after an unexpected clinical procedure and
      input from GPs when difficult clinical decisions are made, such as at the
      beginning or termination of long-term therapies.

PMID- 22162927
TI  - Maspin is a deoxycholate-inducible, anti-apoptotic stress-response protein
      differentially expressed during colon carcinogenesis.
AB  - Increased maspin expression in the colon is related to colon cancer risk and
      patient survival. Maspin is induced by the hydrophobic bile acid, deoxycholate
      (DOC), which is an endogenous carcinogen and inducer of oxidative stress and DNA
      damage in the colon. Persistent exposure of colon epithelial cells, in vitro, to
      high physiologic levels of DOC results in increased constitutive levels of maspin
      protein expression associated with the development of apoptosis resistance. When
      an apoptosis-resistant colon epithelial cell line (HCT-116RC) developed in the
      authors' laboratory was treated with a maspin-specific siRNA probe, there was a
      statistically significant increase in apoptosis compared to treatment with an
      siRNA control probe. These results indicate, for the first time, that maspin is
      an anti-apoptotic protein in the colon. Immunohistochemical evaluation of maspin
      expression in human colonic epithelial cells during sporadic colon carcinogenesis
      (131 human tissues evaluated) indicated a statistically significant increase in
      maspin protein expression beginning at the polyp stage of carcinogenesis. There
      was no statistically significant difference in maspin expression between
      hyperplastic/adenomatous polyps and colonic adenocarcinomas. The absence of
      "field defects" in the non-neoplastic colonic mucosa of patients with colonic
      neoplasia indicates that maspin may drive the growth of tumors, in part, through
      its anti-apoptotic function.

PMID- 22162931
TI  - Exercise-induced bronchospasm: implications for patients with or without asthma
      in primary care practice.
AB  - Exercise-induced bronchospasm (EIB) can represent a substantial barrier to
      physical activity. We present the cases of two patients with EIB, one with
      asthma, and one without asthma, who were evaluated at our primary care practice.
      The first case was a 44-year-old man with a history of seasonal allergic rhinitis
      but no asthma, who reported difficulty breathing when playing tennis. The second
      case was a 45-year-old woman who presented with persistent, generally well
      controlled asthma, who was now experiencing bouts of coughing and wheezing during
      exercise. In both cases, an exercise challenge was used to diagnose EIB, and
      patients were prescribed a short-acting beta agonist to be used immediately
      before initiating exercise. EIB is a frequently encountered problem among
      patients presenting to primary care specialists. Affected patients should be made
      aware of the importance of proactive treatment with a short-acting beta agonist
      before initiating any exercise.

PMID- 22162933
TI  - Allopurinol causing drug rash with eosinophilia and systemic symptoms syndrome: a
      challenging diagnosis.
AB  - BACKGROUND: Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is
      characterized by cutaneous drug eruption, eosinophilia, and systemic symptoms.
      The syndrome is difficult to diagnose due to its clinical heterogeneity and long
      latency period (2-6 weeks). CASE REPORT: This paper describes a 73-year-old man
      who presented with a rash that started 1 week prior to his presentation. The rash
      was associated with fever, dyspnea, and cough. He was admitted for pneumonia and
      started on intravenous antibiotics. After 3 days, he became confused and
      developed multiorgan dysfunction. Work-up for possible hematologic disorders,
      autoimmune diseases, and pneumonia was negative. One month prior to the onset of
      the rash, allopurinol had been prescribed for asymptomatic hyperuricemia. The
      allopurinol was stopped and corticosteroids were started; 2 days later, the
      patient became afebrile and the dyspnea resolved. He was diagnosed with DRESS
      syndrome, which is associated with high mortality. CONCLUSION: The recent
      introduction of a drug followed by a rash, multiorgan dysfunction, and
      eosinophilia should raise the suspicion of DRESS syndrome. Early cessation of the
      introduced drug is key to survival. Clinicians should be aware of this potential
      adverse reaction when prescribing any new drug, including allopurinol.

PMID- 22162932
TI  - Seroprevalence of IgG anti-Toxocara species antibodies in a population of
      patients with suspected allergy.
AB  - BACKGROUND: Toxocara canis is an intestinal nematode affecting dogs and cats,
      which causes human infection when embryonated eggs excreted in dog feces are
      ingested. Humans are paratenic hosts. Although the larvae do not develop into
      adult worms in the human body, they may migrate to various tissues and organs
      where they can survive for several years, giving rise to several clinical
      symptoms, which can present in allergy-like form. METHODS: Over 5 years, we
      examined 9985 patients referred for suspected allergies, based on symptoms such
      as dermatitis, urticaria, rhinitis, asthma, and conjunctivitis; 753 patients who
      had allergy tests negative or unrelated to clinical history were tested for
      seropositivity to T. canis by enzyme-linked immunosorbent assay (ELISA) or
      Western blotting (WB). RESULTS: In 240 patients (31.8%), ELISA or WB or both
      tests were positive for T. canis immunoglobulin G (IgG) antibodies: in
      particular, 64 of them (26.7%) were positive to ELISA, 110 (45.8%) to WB, and 66
      (27.5%) to both tests. Asthma was the most common clinical presentation. Two
      thirds of patients underwent subsequent anthelmintic therapy and showed a
      complete remission of symptoms and, in 43% of patients retested by ELISA and WB,
      became negative to Toxocara. CONCLUSION: These findings strongly suggest that T.
      canis plays a significant role in inducing chronic symptoms presenting as
      suspected allergies.

PMID- 22162934
TI  - A case of cholestatic hepatitis associated with histologic features of acute
      cholangitis.
AB  - This report describes a case showing histologic features of acute cholangitis
      with an over-the-counter drug. A 48-year-old woman was diagnosed with general
      malaise and progressive jaundice. A thorough review of her medical history
      revealed that the patient had taken an over-the-counter drug, Pabron Gold((r)),
      which she had used previously, that may have caused liver injury. Laboratory
      investigations revealed jaundice and liver dysfunction. Endoscopic retrograde
      cholangiography detected no extrahepatic biliary duct dilatation or stones. Liver
      biopsy indicated acute cholangitis involving neutrophils and eosinophils.
      Electron microscopy revealed fragmented nuclei, indicating that the degenerative
      bile duct-related epithelial cells were in an apoptotic process.

PMID- 22162935
TI  - The paradox of the 21st century - is there really an epidemic of most common
      killers?
AB  - Over the last 110 years, average global life expectancy has more than doubled
      from 31 years of age to 65 years of age. This trend is expected to continue, and
      many of the children born after the year 2000 can expect to live to celebrate
      their hundredth birthday. In the last 20 years alone, average life expectancy has
      increased globally by 6 years.DURING THE SAME PERIOD, DOCTORS HAVE ANNOUNCED A
      GLOBAL EPIDEMIC OF THE MOST COMMON KILLERS: cardiovascular disease, diabetes,
      chronic kidney, and chronic obstructive pulmonary disease. One of the most
      important reasons for the more frequent recognition of these diseases is the fact
      that their diagnostic criteria have changed and become much more acute during the
      past few years.These changes in diagnostic criteria have made it difficult, or
      even impossible, to compare the present statistical data regarding these diseases
      to historical data for the same illnesses. Due to this difficulty, there is no
      evidence-based comparison of the prevalence of any disease at present and in the
      past. Before announcing a global epidemic, a fair epidemiological comparison
      should be made, based upon the same definitions and using identical diagnostic
      tools.

PMID- 22162936
TI  - Driving deaths and injuries post-9/11.
AB  - OBJECTIVES: In the days immediately following the terror attacks of 9/11,
      thousands of Americans chose to drive rather than to fly. We analyzed highway
      accident data to determine whether or not the number of fatalities and injuries
      following 9/11 differed from those in the same time period in 2000 and 2002.
      METHODS: Motor crash data from the National Highway Traffic Safety
      Administration's Fatality Analysis Reporting System were analyzed to determine
      the numbers and rates of fatalities and injuries nationally and in selected
      states for the 20 days after September 11, in each of 2000, 2001, and 2002.
      RESULTS: While the fatality rate did not change appreciably, the number of less
      severe injuries was statistically higher in 2001 than in 2000, both nationally
      and in New York State. CONCLUSIONS: The fear of terror attacks may have compelled
      Americans to drive instead of fly. They were thus exposed to the heightened risk
      of injury and death posed by driving. The need for public health to manage risk
      perception and communication is thus heightened in an era of global fear and
      terrorism.

PMID- 22162937
TI  - Predictors for benign paroxysmal positional vertigo with positive Dix-Hallpike
      test.
AB  - OBJECTIVE: Patient medical history is important for making a diagnosis of causes
      of dizziness, but there have been no studies on the diagnostic value of
      individual items in the history. This study was performed to identify and
      validate useful questions for suspecting a diagnosis of benign paroxysmal
      positional vertigo (BPPV). METHODS: Construction and validation of a disease
      prediction model was performed at the outpatient clinic in the Department of
      General Medicine of Chiba University Hospital. Patients with dizziness were
      enrolled (145 patients for construction of the disease prediction model and 61
      patients for its validation). This study targeted BPPV of the posterior
      semicircular canals only with a positive Dix-Hallpike test (DHT + BPPV) to avoid
      diagnostic ambiguity. Binomial logistic regression analysis was performed to
      identify the items that were useful for diagnosis or exclusion of DHT + BPPV.
      RESULTS: Twelve patients from the derivation set and six patients from the
      validation set had DHT + BPPV. Binomial logistic regression analysis selected a
      "duration of dizziness <=15 seconds" and "onset when turning over in bed" as
      independent predictors of DHT + BPPV with an odds ratio (95% confidence interval)
      of 4.36 (1.18-16.19) and 10.17 (2.49-41.63), respectively. Affirmative answers to
      both questions yielded a likelihood ratio of 6.81 (5.11-9.10) for diagnosis of
      DHT + BPPV, while negative answers to both had a likelihood ratio of 0.19 (0.08
      0.47). CONCLUSION: A "duration of dizziness <=15 seconds" and "onset when turning
      over in bed" were the two most important questions among various historical
      features of BPPV.

PMID- 22162938
TI  - Challenges posed to the maternal circulation by pregnancy.
AB  - In primates, adequate growth of the fetus depends on the development of the
      uteroplacental unit. On the fetal side, this is achieved by the creation of the
      vascular network of the placenta. On the maternal side, the transformation of the
      spiral arteries into saccular nonreactive vessels by the trophoblast provides
      high blood flow to the intervillous space. Apart from the changes in the uterine
      arteries, the mother expands her plasma volume - at the expense of stimulating
      the renin-angiotensin-aldosterone system - and her cardiac output. In the
      maintaining of normotension in the face of an increased cardiac output and plasma
      volume, the renin-angiotensin-aldosterone system requires an enhanced vasodilator
      synthesis. Finally, in the late stages of pregnancy, a normal endothelial
      function is required to provide an ample margin to the activation provoked by
      deportation of syncytiotrophoblast fragments/factors to the maternal circulation.
      These four adaptative processes require various interrelated vasodilator systems.
      Deficient adaptations cause isolated or proteinuric arterial hypertension,
      intrauterine growth restriction, preterm delivery, and stillbirths, among others.
      Moreover, a normal or a defective adaptation to pregnancy influences maternal
      cardiovascular health in later life, as evidenced by various studies, most of
      them epidemiological; thus, pregnancy is now considered a stress test to the
      maternal cardiovascular system. Because of this, women planning to become
      pregnant should be screened for clinical and biochemical cardiovascular risks.
      Inversely, women presenting with hypertension in pregnancy should be thoroughly
      studied to detect and correct cardiovascular risks. The incorporation of the
      predictive value of a hypertensive pregnancy should help reduce cardiovascular
      disease in women.

PMID- 22162939
TI  - Combining antihypertensive and antihyperlipidemic agents - optimizing
      cardiovascular risk factor management.
AB  - Clinical guidelines now recognize the importance of a multifactorial approach to
      managing cardiovascular (CV) risk. This idea was taken a step further with the
      concept of the PolypillTM. There are, however, considerable patent,
      pharmacokinetic, pharmacodynamic, registration, and cost implications that will
      need to be overcome before the PolypillTM or other single-pill combinations of CV
      medications become widely available. However, a medication targeting blood
      pressure (BP) and lipids provides much of the proposed benefits of the
      PolypillTM. A single-pill combination of the antihypertensive amlodipine besylate
      and the lipid-lowering medication atorvastatin calcium (SPAA) is currently
      available in many parts of the world. This review describes the rationale for
      this combination therapy and the clinical trials that have demonstrated that
      these two agents can be combined without the loss of efficacy for either agent or
      an increase in the incidence of adverse events. The recently completed Cluster
      Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL
      trial) is discussed in detail. CRUCIAL was a 12-month, international,
      multicenter, prospective, open-label, parallel design, cluster-randomized trial,
      which demonstrated that a proactive intervention strategy based on SPAA in
      addition to usual care (UC) had substantial benefits on estimated CV risk, BP,
      and lipids over continued UC alone. Adherence with antihypertensive and lipid
      lowering therapies outside of the controlled environment of clinical trials is
      very low (~30%-40% at 12 months). Observational studies have demonstrated that
      improving adherence to lipid-lowering and antihypertensive medications may reduce
      CV events. One means of improving adherence is the use of single-pill
      combinations. Real-world observational studies have demonstrated that patients
      are more adherent to SPAA than co-administered antihypertensive and lipid
      lowering therapy, and this improved adherence translated to reduced CV events.
      Taken together, these findings suggest that SPAA can play an important role in
      helping physicians improve the management of CV risk in their patients.

PMID- 22162941
TI  - Representation of Object Orientation in Children: Evidence from Mirror-Image
      Confusions.
AB  - Although many cognitive functions require information about the orientations of
      objects, little is known about representation or processing of object
      orientation. Mirror-image confusion provides a potential clue. This phenomenon is
      typically characterized as a tendency to confuse images related by left-right
      reflection (reflection across an extrinsic vertical axis). However, in most
      previous studies the stimuli were inadequate for identifying a specific mirror
      image (or other) relationship as the cause of the observed confusions. Using
      stimuli constructed to resolve this problem, Gregory and McCloskey (2010) found
      that adults' errors were primarily reflections across an object axis, and not
      left-right reflections. The present study demonstrates that young children's
      orientation errors include both object-axis reflections and left-right
      reflections. We argue that children and adults represent object orientation in
      the same coordinate-system format (McCloskey, 2009), with orientation errors
      resulting from difficulty encoding or retaining one (adults) or two (children)
      specific components of the posited representations.

PMID- 22162942
TI  - The GCP molecular marker toolkit, an instrument for use in breeding food security
      crops.
AB  - Crop genetic resources carry variation useful for overcoming the challenges of
      modern agriculture. Molecular markers can facilitate the selection of
      agronomically important traits. The pervasiveness of genomics research has led to
      an overwhelming number of publications and databases, which are, nevertheless,
      scattered and hence often difficult for plant breeders to access, particularly
      those in developing countries. This situation separates them from developed
      countries, which have better endowed programs for developing varieties. To close
      this growing knowledge gap, we conducted an intensive literature review and
      consulted with more than 150 crop experts on the use of molecular markers in the
      breeding program of 19 food security crops. The result was a list of effectively
      used and highly reproducible sequence tagged site (STS), simple sequence repeat
      (SSR), single nucleotide polymorphism (SNP), and sequence characterized amplified
      region (SCAR) markers. However, only 12 food crops had molecular markers suitable
      for improvement. That is, marker-assisted selection is not yet used for Musa
      spp., coconut, lentils, millets, pigeonpea, sweet potato, and yam. For the other
      12 crops, 214 molecular markers were found to be effectively used in association
      with 74 different traits. Results were compiled as the GCP Molecular Marker
      Toolkit, a free online tool that aims to promote the adoption of molecular
      approaches in breeding activities.

PMID- 22162940
TI  - Computational methods for the identification of microRNA targets.
AB  - MicroRNAs are pivotal regulators of development and cellular homeostasis. They
      act as post-transcriptional regulators, which control the stability and
      translation efficiency of their target mRNAs. The prediction of microRNA targets
      and detection of microRNA-mRNA regulatory modules (MRMs) are crucial components
      for understanding of microRNA functions. Numerous computational methods for
      microRNA target prediction have been developed. Computationally-predicted targets
      have been recently used in the integrative analysis of microRNA and mRNA
      expression analysis to identify microRNA targets and MRMs. In this article we
      review these recent developments in the integrative analysis methods. We also
      discuss the remaining challenges and our insights on future directions.

PMID- 22162943
TI  - Attributions about Addiction among Latina Women.
AB  - This cross-sectional, secondary analysis study utilizes data from a prior study
      of intergenerational substance use among Latina women (n = 316). We explored the
      influence of substance use frequency and type, as well as cultural and
      socioeconomic factors on attributions about addiction among a predominantly
      immigrant sample of Latina women. Women who were less proficient in English (an
      indicator of adoption of the receiving culture in the acculturation process) and
      more proficient in Spanish (an indicator of heritage-culture retention) endorsed
      more spiritual model attributions than women who were more proficient in English
      and less proficient in Spanish. Women were more proficient in Spanish more
      frequently endorsed the disease attribution model. Alcohol, marijuana use and non
      medical sedative use were linked with spiritual, moral /character and disease
      attribution models respectively. Participants reporting higher education levels
      indicated less agreement with the moral/character model of addiction.
      Implications for culturally tailored social work interventions for Latina women
      are discussed.

PMID- 22162944
TI  - Risk factors for homelessness and sex trade among incarcerated women: A
      Structural equation model.
AB  - Incarcerated women are among the most vulnerable and perhaps the least studied
      populations in the US. Significant proportions of female inmates are substance
      users, and many living in unstable housing conditions or being homeless. Female
      inmates are often at high risk of engaging in sex exchange for drugs or housing
      needs. While a disproportionate number of incarcerated women have experienced
      childhood household adversities and maltreatments, the effects of these childhood
      experiences on psychosocial and behavioral outcomes of this population in later
      life. We apply a life course perspective to examine these pathways in a sample of
      incarcerated women in Cook County, Illinois. Findings demonstrated lasting, but
      differential, effects of household adversities and childhood abuse on subsequent
      life risks and opportunities among these women.

PMID- 22162946
TI  - The Open Knowledge Foundation: open data means better science.

PMID- 22162947
TI  - The case of the fickle fingers: how the PRDM9 zinc finger protein specifies
      meiotic recombination hotspots in humans.
AB  - During mammalian meiosis, double-strand breaks are deliberately made throughout
      the genome and then repaired, leading to the exchange of genetic material between
      copies of chromosomes. How the locations of breaks are specified was largely
      unknown until a fortuitous confluence of statistical genetics and molecular
      biology uncovered the role of PRDM9, a DNA binding protein. Many properties of
      this protein remain mysterious, however, including how it binds to DNA, how it
      contributes to male infertility-both in humans, and in hybrid mice-and why, in
      spite of its fundamental function in meiosis, its binding domain varies
      extensively among humans and across mammals. We present a brief summary of what
      has recently been learned about PRDM9 in different fields, focusing on the
      puzzles yet to be resolved.

PMID- 22162948
TI  - Gut microbiota is a key modulator of insulin resistance in TLR 2 knockout mice.
AB  - Environmental factors and host genetics interact to control the gut microbiota,
      which may have a role in the development of obesity and insulin resistance. TLR2
      deficient mice, under germ-free conditions, are protected from diet-induced
      insulin resistance. It is possible that the presence of gut microbiota could
      reverse the phenotype of an animal, inducing insulin resistance in an animal
      genetically determined to have increased insulin sensitivity, such as the TLR2 KO
      mice. In the present study, we investigated the influence of gut microbiota on
      metabolic parameters, glucose tolerance, insulin sensitivity, and signaling of
      TLR2-deficient mice. We investigated the gut microbiota (by metagenomics), the
      metabolic characteristics, and insulin signaling in TLR2 knockout (KO) mice in a
      non-germ free facility. Results showed that the loss of TLR2 in conventionalized
      mice results in a phenotype reminiscent of metabolic syndrome, characterized by
      differences in the gut microbiota, with a 3-fold increase in Firmicutes and a
      slight increase in Bacteroidetes compared with controls. These changes in gut
      microbiota were accompanied by an increase in LPS absorption, subclinical
      inflammation, insulin resistance, glucose intolerance, and later, obesity. In
      addition, this sequence of events was reproduced in WT mice by microbiota
      transplantation and was also reversed by antibiotics. At the molecular level the
      mechanism was unique, with activation of TLR4 associated with ER stress and JNK
      activation, but no activation of the IKKbeta-IkappaB-NFkappaB pathway. Our data
      also showed that in TLR2 KO mice there was a reduction in regulatory T cell in
      visceral fat, suggesting that this modulation may also contribute to the insulin
      resistance of these animals. Our results emphasize the role of microbiota in the
      complex network of molecular and cellular interactions that link genotype to
      phenotype and have potential implications for common human disorders involving
      obesity, diabetes, and even other immunological disorders.

PMID- 22162949
TI  - Microtubules in bacteria: Ancient tubulins build a five-protofilament homolog of
      the eukaryotic cytoskeleton.
AB  - Microtubules play crucial roles in cytokinesis, transport, and motility, and are
      therefore superb targets for anti-cancer drugs. All tubulins evolved from a
      common ancestor they share with the distantly related bacterial cell division
      protein FtsZ, but while eukaryotic tubulins evolved into highly conserved
      microtubule-forming heterodimers, bacterial FtsZ presumably continued to function
      as single homopolymeric protofilaments as it does today. Microtubules have not
      previously been found in bacteria, and we lack insight into their evolution from
      the tubulin/FtsZ ancestor. Using electron cryomicroscopy, here we show that the
      tubulin homologs BtubA and BtubB form microtubules in bacteria and suggest these
      be referred to as "bacterial microtubules" (bMTs). bMTs share important features
      with their eukaryotic counterparts, such as straight protofilaments and similar
      protofilament interactions. bMTs are composed of only five protofilaments,
      however, instead of the 13 typical in eukaryotes. These and other results suggest
      that rather than being derived from modern eukaryotic tubulin, BtubA and BtubB
      arose from early tubulin intermediates that formed small microtubules. Since we
      show that bacterial microtubules can be produced in abundance in vitro without
      chaperones, they should be useful tools for tubulin research and drug screening.

PMID- 22162951
TI  - Gut bacteria may override genetic protections against diabetes.

PMID- 22162950
TI  - MicroRNA-driven developmental remodeling in the brain distinguishes humans from
      other primates.
AB  - While multiple studies have reported the accelerated evolution of brain gene
      expression in the human lineage, the mechanisms underlying such changes are
      unknown. Here, we address this issue from a developmental perspective, by
      analyzing mRNA and microRNA (miRNA) expression in two brain regions within
      macaques, chimpanzees, and humans throughout their lifespan. We find that
      constitutive gene expression divergence (species differences independent of age)
      is comparable between humans and chimpanzees. However, humans display a 3-5 times
      faster evolutionary rate in divergence of developmental patterns, compared to
      chimpanzees. Such accelerated evolution of human brain developmental patterns (i)
      cannot be explained by life-history changes among species, (ii) is twice as
      pronounced in the prefrontal cortex than the cerebellum, (iii) preferentially
      affects neuron-related genes, and (iv) unlike constitutive divergence does not
      depend on cis-regulatory changes, but might be driven by human-specific changes
      in expression of trans-acting regulators. We show that developmental profiles of
      miRNAs, as well as their target genes, show the fastest rates of human-specific
      evolutionary change, and using a combination of computational and experimental
      methods, we identify miR-92a, miR-454, and miR-320b as possible regulators of
      human-specific neural development. Our results suggest that different mechanisms
      underlie adaptive and neutral transcriptome divergence, and that changes in the
      expression of a few key regulators may have been a major driving force behind
      rapid evolution of the human brain.

PMID- 22162952
TI  - Shift work as a risk factor for future type 2 diabetes: evidence, mechanisms,
      implications, and future research directions.

PMID- 22162953
TI  - The primacy of public health considerations in defining poor quality medicines.

PMID- 22162954
TI  - Measuring the population burden of injuries--implications for global and national
      estimates: a multi-centre prospective UK longitudinal study.
AB  - BACKGROUND: Current methods of measuring the population burden of injuries rely
      on many assumptions and limited data available to the global burden of diseases
      (GBD) studies. The aim of this study was to compare the population burden of
      injuries using different approaches from the UK Burden of Injury (UKBOI) and GBD
      studies. METHODS AND FINDINGS: The UKBOI was a prospective cohort of 1,517
      injured individuals that collected patient-reported outcomes. Extrapolated
      outcome data were combined with multiple sources of morbidity and mortality data
      to derive population metrics of the burden of injury in the UK. Participants were
      injured patients recruited from hospitals in four UK cities and towns: Swansea,
      Nottingham, Bristol, and Guildford, between September 2005 and April 2007.
      Patient-reported changes in quality of life using the EQ-5D at baseline, 1, 4,
      and 12 months after injury provided disability weights used to calculate the
      years lived with disability (YLDs) component of disability adjusted life years
      (DALYs). DALYs were calculated for the UK and extrapolated to global estimates
      using both UKBOI and GBD disability weights. Estimated numbers (and rates per
      100,000) for UK population extrapolations were 750,999 (1,240) for hospital
      admissions, 7,982,947 (13,339) for emergency department (ED) attendances, and
      22,185 (36.8) for injury-related deaths in 2005. Nonadmitted ED-treated injuries
      accounted for 67% of YLDs. Estimates for UK DALYs amounted to 1,771,486 (82% due
      to YLDs), compared with 669,822 (52% due to YLDs) using the GBD approach.
      Extrapolating patient-derived disability weights to GBD estimates would increase
      injury-related DALYs 2.6-fold. CONCLUSIONS: The use of disability weights derived
      from patient experiences combined with additional morbidity data on ED-treated
      patients and inpatients suggests that the absolute burden of injury is higher
      than previously estimated. These findings have substantial implications for
      improving measurement of the national and global burden of injury.

PMID- 22162955
TI  - Rotating night shift work and risk of type 2 diabetes: two prospective cohort
      studies in women.
AB  - BACKGROUND: Rotating night shift work disrupts circadian rhythms and has been
      associated with obesity, metabolic syndrome, and glucose dysregulation. However,
      its association with type 2 diabetes remains unclear. Therefore, we aimed to
      evaluate this association in two cohorts of US women. METHODS AND FINDINGS: We
      followed 69,269 women aged 42-67 in Nurses' Health Study I (NHS I, 1988-2008),
      and 107,915 women aged 25-42 in NHS II (1989-2007) without diabetes,
      cardiovascular disease, and cancer at baseline. Participants were asked how long
      they had worked rotating night shifts (defined as at least three nights/month in
      addition to days and evenings in that month) at baseline. This information was
      updated every 2-4 years in NHS II. Self-reported type 2 diabetes was confirmed by
      a validated supplementary questionnaire. We documented 6,165 (NHS I) and 3,961
      (NHS II) incident type 2 diabetes cases during the 18-20 years of follow-up. In
      the Cox proportional models adjusted for diabetes risk factors, duration of shift
      work was monotonically associated with an increased risk of type 2 diabetes in
      both cohorts. Compared with women who reported no shift work, the pooled hazard
      ratios (95% confidence intervals) for participants with 1-2, 3-9, 10-19, and >=20
      years of shift work were 1.05 (1.00-1.11), 1.20 (1.14-1.26), 1.40 (1.30-1.51),
      and 1.58 (1.43-1.74, p-value for trend <0.001), respectively. Further adjustment
      for updated body mass index attenuated the association, and the pooled hazard
      ratios were 1.03 (0.98-1.08), 1.06 (1.01-1.11), 1.10 (1.02-1.18), and 1.24 (1.13
      1.37, p-value for trend <0.001). CONCLUSIONS: Our results suggest that an
      extended period of rotating night shift work is associated with a modestly
      increased risk of type 2 diabetes in women, which appears to be partly mediated
      through body weight. Proper screening and intervention strategies in rotating
      night shift workers are needed for prevention of diabetes.

PMID- 22162956
TI  - Metabolic Abnormalities Associated with the Use of Protease Inhibitors and Non
      nucleoside Reverse Transcriptase Inhibitors.
AB  - The use of protease inhibitors and non-nucleoside reverse transcriptase
      inhibitors for the treatment of HIV infection and AIDS has been associated with
      multiple abnormalities in glucose and lipid metabolism. Specifically, these
      abnormalities include insulin resistance, increased triglycerides and increased
      LDL cholesterol levels. The metabolic disturbances are due to a combination of
      factors, including the direct effect of medications, restoration to health and
      HIV disease, as well as individual genetic predisposition. Of the available anti
      retroviral medications, indinavir has been associated with causing the most
      insulin resistance and ritonavir with causing the most hypertriglyceridemia.

PMID- 22162958
TI  - New Hope: A Thoughtful and Effective Approach to "Make Work Pay"

PMID- 22162959
TI  - Acaricidal and oviposition deterring effects of santalol identified in sandalwood
      oil against two-spotted spider mite, Tetranychus urticae Koch (Acari:
      Tetranychidae).
AB  - Thirty-four plant essential oils were screened for their acaricidal and
      oviposition deterrent activities against two-spotted spider mite (TSSM),
      Tetranychus urticae Koch (Acari: Tetranychidae), in the laboratory using a leaf
      dip bioassay. From initial trials, sandalwood and common thyme oils were observed
      to be the most effective against TSSM adult females. Subsequent trials confirmed
      that only sandalwood oil was significantly active (87.2 +/- 2.9% mortality)
      against TSSM adult females. Sandalwood oil also demonstrated oviposition
      deterring effects based on a 89.3% reduction of the total number of eggs on leaf
      disks treated with the oil. GC-MS analysis revealed that the main components of
      the sandalwood oil were alpha-santalol (45.8%), beta-santalol (20.6%), beta
      sinensal (9.4%), and epi-beta-santalol (3.3%). A mixture of alpha- and beta
      santalol (51.0:22.9, respectively) produced significantly higher mortality (85.5
      +/- 2.9%) and oviposition deterrent effects (94.7% reduction in the number of
      eggs) than the control. Phytotoxicity was not shown on rose shoots to which a
      0.1% solution of sandalwood oil was applied.

PMID- 22162960
TI  - Reflecting biomedical, technological and environmental issues of our modern
      society. The recent "Forum" section in Poiesis & Praxis.

PMID- 22162957
TI  - A tale of two stories: astrocyte regulation of synaptic depression and
      facilitation.
AB  - Short-term presynaptic plasticity designates variations of the amplitude of
      synaptic information transfer whereby the amount of neurotransmitter released
      upon presynaptic stimulation changes over seconds as a function of the neuronal
      firing activity. While a consensus has emerged that the resulting decrease
      (depression) and/or increase (facilitation) of the synapse strength are crucial
      to neuronal computations, their modes of expression in vivo remain unclear.
      Recent experimental studies have reported that glial cells, particularly
      astrocytes in the hippocampus, are able to modulate short-term plasticity but the
      mechanism of such a modulation is poorly understood. Here, we investigate the
      characteristics of short-term plasticity modulation by astrocytes using a
      biophysically realistic computational model. Mean-field analysis of the model,
      supported by intensive numerical simulations, unravels that astrocytes may
      mediate counterintuitive effects. Depending on the expressed presynaptic
      signaling pathways, astrocytes may globally inhibit or potentiate the synapse:
      the amount of released neurotransmitter in the presence of the astrocyte is
      transiently smaller or larger than in its absence. But this global effect usually
      coexists with the opposite local effect on paired pulses: with release-decreasing
      astrocytes most paired pulses become facilitated, namely the amount of
      neurotransmitter released upon spike i+1 is larger than that at spike i, while
      paired-pulse depression becomes prominent under release-increasing astrocytes.
      Moreover, we show that the frequency of astrocytic intracellular Ca(2+)
      oscillations controls the effects of the astrocyte on short-term synaptic
      plasticity. Our model explains several experimental observations yet unsolved,
      and uncovers astrocytic gliotransmission as a possible transient switch between
      short-term paired-pulse depression and facilitation. This possibility has deep
      implications on the processing of neuronal spikes and resulting information
      transfer at synapses.

PMID- 22162961
TI  - Fighting in the legal grey area: an analysis of the German Federal Court of
      Justice decision in case preimplantation genetic diagnosis.
AB  - According to the German Embryo Protection Act, PGD has been banned in Germany
      since 1990; one reason is the legislature's avoiding to insert a revision clause
      regarding medical advance into the law. The ruling of the German Federal Court of
      Justice of July 2010 shows the problems resulting out of this approach and
      declares PGD to be permitted in certain cases. The article discusses the
      necessity for, as well as the problems of, an interdisciplinary dialogue in the
      field of reproductive medicine.

PMID- 22162962
TI  - Privacy revisited? Old ideals, new realities, and their impact on biobank
      regimes.
AB  - Biobanks, collecting human specimen, medical records, and lifestyle-related data,
      face the challenge of having contradictory missions: on the one hand serving the
      collective welfare through easy access for medical research, on the other hand
      adhering to restrictive privacy expectations of people in order to maintain their
      willingness to participate in such research. In this article, ethical frameworks
      stressing the societal value of low-privacy expectations in order to secure
      biomedical research are discussed. It will turn out that neither utilitarian nor
      communitarian or classical libertarian ethics frameworks will help to serve both
      goals. Instead, John Rawls' differentiation of the "right" and the "good" is
      presented in order to illustrate the possibility of "serving two masters":
      individual interests of privacy, and societal interests of scientific progress
      and intergenerational justice. In order to illustrate this counterbalancing
      concept with an example, the five-pillar concept of the German Ethics Council
      will be briefly discussed.

PMID- 22162963
TI  - Service robotics: do you know your new companion? Framing an interdisciplinary
      technology assessment.
AB  - Service-Robotic-mainly defined as "non-industrial robotics"-is identified as the
      next economical success story to be expected after robots have been ubiquitously
      implemented into industrial production lines. Under the heading of service
      robotic, we found a widespread area of applications reaching from robotics in
      agriculture and in the public transportation system to service robots applied in
      private homes. We propose for our interdisciplinary perspective of technology
      assessment to take the human user/worker as common focus. In some cases, the
      user/worker is the effective subject acting by means of and in cooperation with a
      service robot; in other cases, the user/worker might become a pure object of the
      respective robotic system, for example, as a patient in a hospital. In this
      paper, we present a comprehensive interdisciplinary framework, which allows us to
      scrutinize some of the most relevant applications of service robotics; we propose
      to combine technical, economical, legal, philosophical/ethical, and psychological
      perspectives in order to design a thorough and comprehensive expert-based
      technology assessment. This allows us to understand the potentials as well as the
      limits and even the threats connected with the ongoing and the planned
      implementation of service robots into human lifeworld-particularly of those
      technical systems displaying increasing grades of autonomy.

PMID- 22162964
TI  - Rainforest conservation as a strategy of climate policy.
AB  - Tropical forest conservation in developing countries has repeatedly been
      highlighted as a new element in international climate policy. However, no clear
      ideas yet exist as to what shape such a conservation strategy might take. In the
      present paper, we would like to make some observations to this end. It is shown
      how projects in order to reduce CO(2)-emissions resulting from deforestation and
      degradation (REDD) can be integrated into a system of tradable emission rights in
      an industrialised country and which requirements ought to be fulfilled.
      Instruments are emission credits and emission allowances. Driving actors
      interested in emission rights through forest projects may be private investors or
      the rainforest state itself. The efficiency of the system depends on a great
      extent on a binding reference path for the tolerable emissions from
      deforestation, which has been agreed upon and adhered to by the rainforest
      country by means of a forest law aimed at limiting deforestation. Our
      considerations lead us to conclude that the national baseline approach with an
      appropriate contribution by the rainforest country coupled with a decentralised
      system with private investors seems the most viable option. Since additional
      burdens are imposed on the rainforest country to some extent, a compromise could
      consist of agreeing on a moderate deforestation path, which is harmonised with
      the benefits from the forest projects. Combining both programmes (offset credits
      and emission allowances) is particularly attractive because all participants, and
      especially the industrialised country, benefit from it. The industrialised
      country can expand its climate conservation programme without any additional
      costs to a certain degree.

PMID- 22162965
TI  - Experience with low-cost telemedicine in three different settings.
      Recommendations based on a proposed framework for network performance evaluation.
AB  - BACKGROUND: Telemedicine has been used for many years to support doctors in the
      developing world. Several networks provide services in different settings and in
      different ways. However, to draw conclusions about which telemedicine networks
      are successful requires a method of evaluating them. No general consensus or
      validated framework exists for this purpose. OBJECTIVE: To define a basic method
      of performance measurement that can be used to improve and compare
      teleconsultation networks; to employ the proposed framework in an evaluation of
      three existing networks; to make recommendations about the future implementation
      and follow-up of such networks. METHODS: Analysis based on the experience of
      three telemedicine networks (in operation for 7-10 years) that provide services
      to doctors in low-resource settings and which employ the same basic design.
      FINDINGS: Although there are many possible indicators and metrics that might be
      relevant, five measures for each of the three user groups appear to be sufficient
      for the proposed framework. In addition, from the societal perspective,
      information about clinical- and cost-effectiveness is also required. The proposed
      performance measurement framework was applied to three mature telemedicine
      networks. Despite their differences in terms of activity, size and objectives,
      their performance in certain respects is very similar. For example, the time to
      first reply from an expert is about 24 hours for each network. Although all three
      networks had systems in place to collect data from the user perspective, none of
      them collected information about the coordinator's time required or about ease of
      system usage. They had only limited information about quality and cost.
      CONCLUSION: Measuring the performance of a telemedicine network is essential in
      understanding whether the network is working as intended and what effect it is
      having. Based on long-term field experience, the suggested framework is a
      practical tool that will permit organisations to assess the performance of their
      own networks and to improve them by comparison with others. All telemedicine
      systems should provide information about setup and running costs because cost
      effectiveness is crucial for sustainability.

PMID- 22162966
TI  - The Current Status of Neural Grafting in the Treatment of Huntington's Disease. A
      Review.
AB  - Huntington's disease (HD) is a devastating, fatal, autosomal dominant condition
      in which the abnormal gene codes for a mutant form of huntingtin that causes
      widespread neuronal dysfunction and death. This leads to a clinical presentation,
      typically in midlife, with a combination of motor, psychiatric, cognitive,
      metabolic, and sleep abnormalities, for which there are some effective
      symptomatic therapies that can produce some transient benefits. The disease,
      though, runs a progressive course over a 20-year period ultimately leading to
      death, and there are currently no proven disease modifying therapies. However
      whilst the neuronal dysfunction and loss affects much of the central nervous
      system, the striatum is affected early on in the disease and is one of the areas
      most affected by the pathogenic process. As a result the prospect of treating HD
      using neural transplants of striatal tissue has been explored and to date the
      clinical data is inconclusive. In this review we discuss the rationale for
      treating HD using this approach, before discussing the clinical trial data and
      what we have learnt to date using this therapeutic strategy.

PMID- 22162967
TI  - Visual Experiences during Paralysis.
AB  - RATIONALE: Paralyzed human volunteers (n = 6) participated in several studies the
      primary one of which required full neuromuscular paralysis while awake. After the
      primary experiment, while still paralyzed and awake, subjects undertook studies
      of humor and of attempted eye-movement. The attempted eye-movements tested a
      central, intentional component to one's internal visual model and are the subject
      of this report. METHODS: Subjects reclined in a supportive chair and were
      ventilated after paralysis (cisatracurium, 20 mg intravenously). In illumination,
      subjects were requested to focus alternately on the faces of investigators
      standing on the left and the right within peripheral vision. In darkness,
      subjects were instructed to look away from a point source of light. Subjects were
      to report their experiences after reversal of paralysis. RESULTS: During
      attempted eye-movement in illumination, one subject had an illusion of
      environmental movement but four subjects perceived faces as clearly as if they
      were in central vision. In darkness, four subjects reported movement of the
      target light in the direction of attempted eye-movements and three could control
      the movement of the light at will. CONCLUSION: The hypothesis that internal
      visual models receive intended ocular-movement-information directly from
      oculomotor centers is strengthened by this evidence.

PMID- 22162968
TI  - Callosal connections of primary visual cortex predict the spatial spreading of
      binocular rivalry across the visual hemifields.
AB  - In binocular rivalry, presentation of different images to the separate eyes leads
      to conscious perception alternating between the two possible interpretations
      every few seconds. During perceptual transitions, a stimulus emerging into
      dominance can spread in a wave-like manner across the visual field. These
      traveling waves of rivalry dominance have been successfully related to the
      cortical magnification properties and functional activity of early visual areas,
      including the primary visual cortex (V1). Curiously however, these traveling
      waves undergo a delay when passing from one hemifield to another. In the current
      study, we used diffusion tensor imaging (DTI) to investigate whether the strength
      of interhemispheric connections between the left and right visual cortex might be
      related to the delay of traveling waves across hemifields. We measured the delay
      in traveling wave times (DeltaTWT) in 19 participants and repeated this test 6
      weeks later to evaluate the reliability of our behavioral measures. We found
      large interindividual variability but also good test-retest reliability for
      individual measures of DeltaTWT. Using DTI in connection with fiber tractography,
      we identified parts of the corpus callosum connecting functionally defined visual
      areas V1-V3. We found that individual differences in DeltaTWT was reliably
      predicted by the diffusion properties of transcallosal fibers connecting left and
      right V1, but observed no such effect for neighboring transcallosal visual fibers
      connecting V2 and V3. Our results demonstrate that the anatomical characteristics
      of topographically specific transcallosal connections predict the individual
      delay of interhemispheric traveling waves, providing further evidence that V1 is
      an important site for neural processes underlying binocular rivalry.

PMID- 22162970
TI  - Enhanced dopamine D1 and BDNF signaling in the adult dorsal striatum but not
      nucleus accumbens of prenatal cocaine treated mice.
AB  - Previous work from our group and others utilizing animal models have demonstrated
      long-lasting structural and functional alterations in the meso-cortico-striatal
      dopamine pathway following prenatal cocaine (PCOC) treatment. We have shown that
      PCOC treatment results in augmented D1-induced cyclic AMP (cAMP) and cocaine
      induced immediate-early gene expression in the striatum of adult mice. In this
      study we further examined basal as well as cocaine or D1-induced activation of a
      set of molecules known to be mediators of neuronal plasticity following
      psychostimulant treatment, with emphasis in the dorsal striatum (Str) and nucleus
      accumbens (NAc) of adult mice exposed to cocaine in utero. Basally, in the Str of
      PCOC treated mice there were significantly higher levels of (1) CREB and Ser133 P
      CREB (2) Thr34 P-DARPP-32 and (3) GluA1 and Ser 845 P-GluA1 when compared to
      prenatal saline (PSAL) treated mice. In the NAc there were significantly higher
      basal levels of (1) CREB and Ser133 P-CREB, (2) Thr202/Tyr204 P-ERK2, and (3)
      Ser845 P-GluA1. Following acute administration of cocaine (15 mg/kg, i.p.) or D1
      agonist (SKF 82958; 1 mg/kg, i.p.) there were significantly higher levels of
      Ser133 P-CREB, Thr34 P-DARPP-32, and Thr202/Tyr204 P-ERK2 in the Str that were
      evident in all animals tested. However, these cocaine-induced increases in
      phosphorylation were significantly augmented in PCOC mice compared to PSAL mice.
      In sharp contrast to the observations in the Str, in the NAc, acute
      administration of cocaine or D1 agonist significantly increased P-CREB and P-ERK2
      in PSAL mice, a response that was not evident in PCOC mice. Examination of Ser
      845 P-GluA1 revealed that cocaine or D1 agonist significantly increased levels in
      PSAL mice, but significantly decreased levels in the PCOC mice in both the Str
      and NAc. We also examined changes in brain-derived neurotrophic factor (BDNF).
      Our studies revealed significantly higher levels of the BDNF precursor, pro-BDNF,
      and one of its receptors, TrkB in the Str of PCOC mice compared to PSAL mice.
      These results suggest a persistent up-regulation of molecules critical to D1 and
      BDNF signaling in the Str of adult mice exposed to cocaine in utero. These
      molecular adaptations may underlie components of the behavioral deficits evident
      in exposed animals and a subset of exposed humans, and may represent a
      therapeutic target for ameliorating aspects of the PCOC-induced phenotype.

PMID- 22162969
TI  - Brain-gut-microbe communication in health and disease.
AB  - Bidirectional signalling between the gastrointestinal tract and the brain is
      regulated at neural, hormonal, and immunological levels. This construct is known
      as the brain-gut axis and is vital for maintaining homeostasis. Bacterial
      colonization of the intestine plays a major role in the post-natal development
      and maturation of the immune and endocrine systems. These processes are key
      factors underpinning central nervous system (CNS) signaling. Recent research
      advances have seen a tremendous improvement in our understanding of the scale,
      diversity, and importance of the gut microbiome. This has been reflected in the
      form of a revised nomenclature to the more inclusive brain-gut-enteric microbiota
      axis and a sustained research effort to establish how communication along this
      axis contributes to both normal and pathological conditions. In this review, we
      will briefly discuss the critical components of this axis and the methodological
      challenges that have been presented in attempts to define what constitutes a
      normal microbiota and chart its temporal development. Emphasis is placed on the
      new research narrative that confirms the critical influence of the microbiota on
      mood and behavior. Mechanistic insights are provided with examples of both neural
      and humoral routes through which these effects can be mediated. The evidence
      supporting a role for the enteric flora in brain-gut axis disorders is explored
      with the spotlight on the clinical relevance for irritable bowel syndrome, a
      stress-related functional gastrointestinal disorder. We also critically evaluate
      the therapeutic opportunities arising from this research and consider in
      particular whether targeting the microbiome might represent a valid strategy for
      the management of CNS disorders and ponder the pitfalls inherent in such an
      approach. Despite the considerable challenges that lie ahead, this is an exciting
      area of research and one that is destined to remain the center of focus for some
      time to come.

PMID- 22162971
TI  - Cognitive and affective control in insomnia.
AB  - Insomnia is a prevalent disabling chronic disorder. The aim of this paper is
      fourfold: (a) to review evidence suggesting that dysfunctional forms of cognitive
      control, such as thought suppression, worry, rumination, and imagery control, are
      associated with sleep disturbance; (b) to review a new budding field of
      scientific investigation - the role of dysfunctional affect control in sleep
      disturbance, such as problems with down-regulating negative and positive
      affective states; (c) to review evidence that sleep disturbance can impair next
      day affect control; and (d) to outline, on the basis of the reviewed evidence,
      how the repetitive-thought literature and the affective science literature can be
      combined to further understanding of, and intervention for, insomnia.

PMID- 22162972
TI  - Spatial distribution of the attentional blink.
AB  - In the present study subjects viewed streams of rapid serially presented
      characters and searched for a target digit. After presentation of the target
      digit, a second target consisting of an orientation singleton (Experiment 1) or a
      second digit (Experiment 2) was presented at one of several distances from the
      first target. The attentional blink (AB) impaired performance on the second
      target with the effect being strongest at distances somewhat removed from the
      first target location. These results are consistent with lateral inhibition
      theory and help to resolve some fundamental questions about the spatial
      distribution of the AB.

PMID- 22162973
TI  - Four common conceptual fallacies in mapping the time course of recognition.
AB  - Determining the moment at which a visual recognition process is completed, or the
      order in which various processes come into play, are fundamental steps in any
      attempt to understand human recognition abilities, or to replicate the
      corresponding hierarchy of neuronal mechanisms within artificial systems. Common
      experimental paradigms for addressing these questions involve the measurement
      and/or comparison of backward-masking (or rapid serial visual presentation)
      psychometric functions and of physiological EEG/MEG/LFP signals (peak latencies,
      differential activities, single-trial decoding techniques). I review and
      illustrate four common mistakes that scientists tend to make when using these
      paradigms, and explain the conceptual fallacies that motivate their reasoning.
      First, contrary to collective intuition, presentation times, or stimulus-onset
      asynchrony masking thresholds cannot be taken to reflect, directly or indirectly,
      the timing of relevant brain processes. Second, psychophysical or
      electrophysiological measurements should not be compared without assessing
      potential physical differences between experimental stimulus sets. Third, such
      comparisons should not be performed in any manner contingent on subjective
      responses, so as to avoid response biases. Last, the filtering of
      electrophysiological signals alters their temporal structure, and thus precludes
      their interpretation in terms of time course. Practical solutions are proposed to
      overcome these common mistakes.

PMID- 22162974
TI  - What is Depression in Epilepsy?

PMID- 22162975
TI  - Synthesis and characterization of a biodegradable elastomer featuring a dual
      crosslinking mechanism.
AB  - The need for advanced materials in emerging technologies such as tissue
      engineering has prompted increased research to produce novel biodegradable
      polymers elastic in nature and mechanically compliant with the host tissue. We
      have developed a soft biodegradable elastomeric platform biomaterial created from
      citric acid, maleic anhydride, and 1,8-octanediol, poly(octamethylene maleate
      (anhydride) citrate) (POMaC), which is able to closely mimic the mechanical
      properties of a wide range of soft biological tissues. POMaC features a dual
      crosslinking mechanism, which allows for the option of the crosslinking POMaC
      using UV irradiation and/or polycondensation to fit the needs of the intended
      application. The material properties, degradation profiles, and functionalities
      of POMaC thermoset networks can all be tuned through the monomer ratios and the
      dual crosslinking mechanism. POMaC polymers displayed an initial modulus between
      0.03 and 1.54 MPa, and elongation at break between 48% and 534% strain. In vitro
      and in vivo evaluation using cell culture and subcutaneous implantation,
      respectively, confirmed cell and tissue biocompatibility. POMaC biodegradable
      polymers can also be combined with MEMS technology to fabricate soft and elastic
      3D microchanneled scaffolds for tissue engineering applications. The introduction
      of POMaC will expand the choices of available biodegradable polymeric elastomers.
      The dual crosslinking mechanism for biodegradable elastomer design should
      contribute to biomaterials science.

PMID- 22162976
TI  - The lived experience of stroke survivors with early depressive symptoms: A
      longitudinal perspective.
AB  - PURPOSE: The aim of the study was to describe the lived experience as it develops
      over time in stroke survivors suffering from early depressive symptoms. METHOD:
      This paper presents a phenomenological hermeneutical interview-study of nine
      participants at 6, 12, and 18 months after stroke. FINDINGS: The participants
      related the depressive symptoms to the consequences of the stroke, and the
      experience of loss was crucial. Depressive symptoms was not meaningful on its
      own, but formed the backdrop of the experience of stroke. Our findings revealed
      three patterns of experience: (1) finding a restored self; (2) trapped in a
      different life; and (3) fighting to regain self. TWO GROUPS OF STROKE SURVIVORS
      ARE PARTICULARLY VULNERABLE AND SHOULD RECEIVE SPECIAL ATTENTION: (a) old adults
      living alone; and (b) adults experiencing serious threats to their commitments
      such as to work, family, and children. CONCLUSION: Depressive symptoms have a
      severe impact on life after stroke. Life circumstances, degree of residual
      impairment from a stroke, and social context were found to influence people to
      move along different paths. Older adults living alone and adults experiencing
      serious threat to their commitments should receive special attention, in terms of
      further research and in terms of follow-up in clinical practice. More studies
      investigating the experience of post-stroke depression (PSD) over time and the
      association between depressive symptoms and loss/grieving are needed. There is
      also a need for continued empirical research on the identification of effective
      interventions aimed at prevention or improved coping with PSD.

PMID- 22162977
TI  - Advanced MRI of articular cartilage.
AB  - Musculoskeletal MRI is advancing rapidly, with innovative technology and
      significant potential for immediate clinical impact. In particular, cartilage
      imaging has become a topic of increasing interest as our aging population
      develops diseases such as osteoarthritis. Advances in MRI hardware and software
      have led to increased image quality and tissue contrast. Additional developments
      have allowed the assessment of cartilage macromolecular content, which may be
      crucial to the early detection of musculoskeletal diseases. This comprehensive
      article considers current morphological and physiological cartilage imaging
      techniques, their clinical applications, and their potential to contribute to
      future improvements in the imaging of cartilage.

PMID- 22162978
TI  - Atherogenic dyslipidemia and cardiovascular risk in children with nonalcoholic
      fatty liver disease.
AB  - Nonalcoholic fatty liver disease is now regarded as the most common form of
      chronic liver disease in adults and children. The close association between
      nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome has been
      extensively described. Moreover, a growing body of evidence suggest that NAFLD by
      itself confers a substantial cardiovascular risk independent of the other
      components of the metabolic syndrome. Given the significant potential for
      morbidity and mortality in these patients, and the large proportion of both
      pediatric and adult population affected, it is important that we clearly define
      the overall risk, identify early predictors for cardiovascular disease
      progression, and establish management strategies. In this article, we will focus
      on current data linking NAFLD and the severity of liver damage present in
      children with cardiovascular risk.

PMID- 22162979
TI  - Clinical applications of advanced lipoprotein testing in diabetes mellitus.
AB  - Traditional lipid profiles often fail to fully explain the elevated
      cardiovascular risk of individuals with diabetes mellitus. Advanced lipoprotein
      testing offers a novel means to evaluate dyslipidemia and refine risk estimation.
      Numerous observational studies have demonstrated a characteristic pattern of
      elevated levels of small, dense LDL particles, out of proportion to traditional
      lipid levels, in patients with both diabetes mellitus and the metabolic syndrome.
      Commonly used glucose and lipid-lowering agents have varied effects in patients
      with diabetes on both LDL and HDL subfractions. The exact role of advanced
      lipoprotein testing in patients with diabetes mellitus and the metabolic syndrome
      remains unclear but may offer improved assessment of cardiovascular risk compared
      with traditional lipid measurements.

PMID- 22162981
TI  - Transoral robotic-assisted thyroidectomy with central neck dissection:
      preclinical cadaver feasibility study and proposed surgical technique.
AB  - Recently, a transoral robotic-assisted technique to access the thyroid gland has
      been introduced. Despite the advantages this approach may have over other
      minimally invasive and robotic-assisted techniques, we found that the placement
      of the camera through the floor of mouth led to restricted freedom of movement.
      We describe our modification to this technique to overcome this problem. In a
      study using two fresh human cadavers, the camera port of the da Vinci robot was
      placed in the midline oral vestibule instead of the floor of the mouth. A
      transoral thyroidectomy and central neck dissection was successfully performed.
      Our modification led to an unfettered view of the central neck and allowed for a
      total thyroidectomy and central neck dissection. Our modification of transoral
      robotic-assisted thyroidectomy provides superior access to the central
      compartment of the neck over other robotic-assisted thyroidectomy techniques.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11701-011-0287-2) contains supplementary material, which is
      available to authorized users.

PMID- 22162982
TI  - Neuroevolutionary reinforcement learning for generalized control of simulated
      helicopters.
AB  - This article presents an extended case study in the application of neuroevolution
      to generalized simulated helicopter hovering, an important challenge problem for
      reinforcement learning. While neuroevolution is well suited to coping with the
      domain's complex transition dynamics and high-dimensional state and action
      spaces, the need to explore efficiently and learn on-line poses unusual
      challenges. We propose and evaluate several methods for three increasingly
      challenging variations of the task, including the method that won first place in
      the 2008 Reinforcement Learning Competition. The results demonstrate that (1)
      neuroevolution can be effective for complex on-line reinforcement learning tasks
      such as generalized helicopter hovering, (2) neuroevolution excels at finding
      effective helicopter hovering policies but not at learning helicopter models, (3)
      due to the difficulty of learning reliable models, model-based approaches to
      helicopter hovering are feasible only when domain expertise is available to aid
      the design of a suitable model representation and (4) recent advances in
      efficient resampling can enable neuroevolution to tackle more aggressively
      generalized reinforcement learning tasks.

PMID- 22162980
TI  - Lysophosphatidic acid effects on atherosclerosis and thrombosis.
AB  - Lysophosphatidic acid (LPA) has been found to accumulate in high concentrations
      in atherosclerotic lesions. LPA is a bioactive phospholipid produced by activated
      platelets and formed during the oxidation of LDL. Accumulating evidence suggests
      that this lipid mediator may serve as an important risk factor for development of
      atherosclerosis and thrombosis. The role of LPA in atherogenesis is supported by
      the evidence that LPA: stimulates endothelial cells to produce adhesion molecules
      and chemoattractants; induces smooth muscle cells to produce inflammatory
      cytokines; stimulates smooth muscle cell dedifferentiation, proliferation, and
      migration; increases monocyte migration and decreases monocyte-derived cell
      emigration from the vessel wall; induces hypertension and vascular neointimal
      formation in vivo; and promotes plaque progression in a mouse atherosclerosis
      model. The role of LPA in thrombogenesis is supported by the evidence that LPA
      markedly induces the aggregation of platelets and the expression of tissue
      factor, which is the principal initiator of blood coagulation. Recent
      experimental data indicate that LPA is produced by specific enzymes and that LPA
      binds to and activates multiple G-protein-coupled receptors, leading to
      intracellular signaling. Therapeutics targeting LPA biosynthesis, metabolism and
      signaling pathways could be viable for prevention and treatment of
      atherosclerosis and thrombosis.

PMID- 22162983
TI  - Characterization of intestinal dendritic cells in murine norovirus infection.
AB  - We have shown that respiratory viral infections drive allergic disease through
      dendritic cells, whether gastrointestinal viruses induce allergies is not known.
      Norovirus infections are a major cause of gastroenteritis in humans. We used
      murine norovirus (MNV) to explore the effect of MNV infection on gastrointestinal
      conventional DCs (cDCs) and plasmacytoid DCs (pDCs). MNV infection induced
      disparate effects on cDCs and pDCs in lymphoid tissues of the small intestine and
      draining mesenteric lymph nodes. FcepsilonRI was transiently expressed on lamina
      propria cDCs, but not on pDCs. In addition, feeding ovalbumin during the viral
      infection led to a modest, brief induction of anti-ovalbumin IgE. Together, these
      data suggest that like with a respiratory viral infection, an intestinal viral
      infection may be sufficient to induce changes in DCs and the generation of food
      specific IgE. Whether this represents a novel mechanism of food allergy remains
      to be determined.

PMID- 22162984
TI  - Targeting Bcl-2 in Herceptin-Resistant Breast Cancer Cell Lines.
AB  - Acquired resistance to Herceptin is a major clinical problem in the treatment of
      HER2-overexpressing breast cancer. Understanding the molecular mechanisms leading
      to resistance will allow identification of novel therapeutic targets and
      predictors of therapeutic response. To this end, up-regulation of anti-apoptotic
      proteins has been associated with resistance to the HER2-targeted drug lapatinib,
      but has not yet been linked to Herceptin resistance. The aim of the current study
      was to determine if the Bcl-2 anti-apoptotic protein is a potential therapeutic
      target in cells with acquired Herceptin resistance. The BT474 HER2-overexpressing
      breast cancer cell line and BT474-derived acquired Herceptin-resistant clones
      were used as models in this study. Bcl-2 and Bax expression were assessed by
      Western blotting. Proliferation assays were performed on cells treated with the
      Bcl-2 inhibitor ABT-737 in the absence or presence of Herceptin. Finally, the
      effect of PI3K inhibition or IKK inhibition on Bcl-2 expression and Herceptin
      sensitivity was examined by Western blotting and established proliferation
      assays. We show that cells with acquired resistance to Herceptin have an
      increased Bcl-2:Bax ratio. Resistant cells have increased sensitivity to ABT-737.
      Further, pharmacologic inhibition of Bcl-2 improved sensitivity to Herceptin in
      acquired resistant cells. Finally, PI3K and IKK inhibition down-regulated Bcl-2
      expression and increased sensitivity to Herceptin in resistant cells. Taken
      together, these new observations support further study of Bcl-2-targeted
      therapies in Herceptin-resistant breast cancers, and importantly, future
      investigation of Bcl-2 expression as a potential predictor of Herceptin response
      in patients with HER2-overexpressing breast cancer.

PMID- 22162985
TI  - Drug resistance in HIV-1.
AB  - PURPOSE OF THE REVIEW: Changing antiretroviral regimens and the introduction of
      new antiretroviral drugs have altered drug resistance patterns in human
      immunodeficiency virus type 1 (HIV-1). This review summarizes recent information
      on antiretroviral drug resistance. RECENT FINDINGS: As tenofovir and abacavir
      have replaced zidovudine and stavudine in antiretroviral regimens, thymidine
      analog resistance mutations have become less common in patients failing
      antiretroviral therapy in developed countries. Similarly, the near universal use
      of ritonavir-boosted protease inhibitors (PI) in place of unboosted PIs has made
      the selection of PI resistance mutations uncommon in patients failing a first
      line or second-line PI regimen. The challenge of treating patients with multidrug
      resistant HIV-1 has largely been addressed by the advent of newer PIs, second
      generation non-nucleoside reverse transcriptase inhibitors and drugs in novel
      classes, including integrase inhibitors and CCR5 antagonists. Resistance to these
      newer agents can emerge, however, resulting in the appearance of novel drug
      resistance mutations in the HIV-1 polymerase, integrase and envelope genes.
      SUMMARY: New drugs make possible the effective treatment of multidrug-resistant
      HIV-1, but the activity of these drugs may be limited by the appearance of novel
      drug resistance mutations.

PMID- 22162986
TI  - BAYESIAN HIERARCHICAL MODELING FOR SIGNALING PATHWAY INFERENCE FROM SINGLE CELL
      INTERVENTIONAL DATA.
AB  - Recent technological advances have made it possible to simultaneously measure
      multiple protein activities at the single cell level. With such data collected
      under different stimulatory or inhibitory conditions, it is possible to infer the
      causal relationships among proteins from single cell interventional data. In this
      article we propose a Bayesian hierarchical modeling framework to infer the
      signaling pathway based on the posterior distributions of parameters in the
      model. Under this framework, we consider network sparsity and model the existence
      of an association between two proteins both at the overall level across all
      experiments and at each individual experimental level. This allows us to infer
      the pairs of proteins that are associated with each other and their causal
      relationships. We also explicitly consider both intrinsic noise and measurement
      error. Markov chain Monte Carlo is implemented for statistical inference. We
      demonstrate that this hierarchical modeling can effectively pool information from
      different interventional experiments through simulation studies and real data
      analysis.

PMID- 22162988
TI  - The cost-effectiveness and value of information of three influenza vaccination
      dosing strategies for individuals with human immunodeficiency virus.
AB  - BACKGROUND: Influenza vaccine immunogenicity is diminished in patients living
      with HIV/AIDS. We evaluated the cost-effectiveness and expected value of perfect
      information (EVPI) of three alternative influenza vaccine dosing strategies
      intended to increase immunogenicity in those patients. METHODS: A randomized,
      multi-centered, controlled, vaccine trial was conducted at 12 CIHR Canadian HIV
      Trials Network sites. Three dosing strategies with seasonal, inactivated
      trivalent, non-adjuvanted intramuscular vaccine were used in HIV infected adults:
      two standard doses over 28 days (Strategy A), two double doses over 28 days
      (Strategy B) and a single standard dose of influenza vaccine (Strategy C),
      administered prior to the 2008 influenza season. The comparator in our analysis
      was practice in the previous year, in which 82.8% of HIV/AIDS received standard
      dose vaccination (Strategy D). A Markov cohort model was developed to estimate
      the monthly probability of Influenza-like Illness (ILI) over one influenza
      season. Costs and quality-adjusted life years, extrapolated to the lifetime of
      the hypothetical study cohorts, were estimated in calculating incremental cost
      effectiveness ratios (ICER) and EVPI in conducting further research. RESULTS: 298
      patients with median CD4 of 470 cells/ul and 76% with viral load suppression were
      randomized. Strategy C was the most cost-effective strategy for the overall trial
      population and for suppressed and unsuppressed individuals. Mean ICERs for
      Strategy A for unsuppressed patients could also be considered cost-effective. The
      level of uncertainty regarding the decision to implement strategy A versus C for
      unsuppressed individuals was high. The maximum acceptable cost of reducing
      decision uncertainty in implementing strategy A for individuals with unsuppressed
      pVL was $418,000--below the cost of conducting a larger-scale trial. CONCLUSION:
      Our results do not support a policy to implement increased antigen dose or
      booster dosing strategies with seasonal, inactivated trivalent, non-adjuvanted
      intramuscular vaccine for individuals with HIV in Canada. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00764998.

PMID- 22162989
TI  - Use of the D-R model to define trends in the emergence of Ceftazidime-resistant
      Escherichia coli in China.
AB  - OBJECTIVE: To assess the efficacy of the D-R model for defining trends in the
      appearance of Ceftazidime-resistant Escherichia coli. METHODS: Actual data
      related to the manifestation of Ceftazidime-resistant E. coli spanning years 1996
      2009 were collected from the China National Knowledge Internet. These data
      originated from 430 publications encompassing 1004 citations of resistance. The
      GM(1,1) and the novel D-R models were used to fit current data and from this,
      predict trends in the appearance of the drug-resistant phenotype. The results
      were evaluated by Relative Standard Error (RSE), Mean Absolute Deviation (MAD)
      and Mean Absolute Error (MAE). RESULTS: Results from the D-R model showed a rapid
      increase in the appearance of Ceftazidime-resistant E. coli in this region of the
      world. These results were considered accurate based upon the minor values
      calculated for RSE, MAD and MAE, and were equivalent to or better than those
      generated by the GM(1,1) model. CONCLUSION: The D-R model which was originally
      created to define trends in the transmission of swine viral diseases can be
      adapted to evaluating trends in the appearance of Ceftazidime-resistant E. coli.
      Using only a limited amount of data to initiate the study, our predictions
      closely mirrored the changes in drug resistance rates which showed a steady
      increase through 2005, a decrease between 2005 and 2008, and a dramatic
      inflection point and abrupt increase beginning in 2008. This is consistent with a
      resistance profile where changes in drug intervention temporarily delayed the
      upward trend in the appearance of the resistant phenotype; however, resistance
      quickly resumed its upward momentum in 2008 and this change was better predicted
      using the D-R model. Additional work is needed to determine if this pattern of
      "increase-control-increase" is indicative of Ceftazidime-resistant E. coli or can
      be generally ascribed to bacteria acquiring resistance to drugs in the absence of
      alternative intervention.

PMID- 22162990
TI  - Psychophysiological responses to stress after stress management training in
      patients with rheumatoid arthritis.
AB  - BACKGROUND: Stress management interventions may prove useful in preventing the
      detrimental effects of stress on health. This study assessed the effects of a
      stress management intervention on the psychophysiological response to stress in
      patients with rheumatoid arthritis (RA). METHODS: Seventy-four patients with RA,
      who were randomly assigned to either a control group or a group that received
      short-term stress management training, performed a standardized psychosocial
      stress task (Trier Social Stress Test; TSST) 1 week after the stress management
      training and at a 9-week follow-up. Psychological and physical functioning, and
      the acute psychophysiological response to the stress test were assessed. RESULTS:
      Patients in the intervention group showed significantly lower psychological
      distress levels of anxiety after the training than did the controls. While there
      were no between-group differences in stress-induced tension levels, and autonomic
      (alpha-amylase) or endocrine (cortisol) responses to the stress test 1 week after
      the intervention, levels of stress-induced tension and cortisol were
      significantly lower in the intervention group at the 9-week follow-up. Overall,
      the response to the intervention was particularly evident in a subgroup of
      patients with a psychological risk profile. CONCLUSION: A relatively short stress
      management intervention can improve psychological functioning and influences the
      psychophysiological response to stress in patients with RA, particularly those
      psychologically at risk. These findings might help understand how stress can
      affect health and the role of individual differences in stress responsiveness.
      TRIAL REGISTRATION: TrialRegister.nl NTR1193.

PMID- 22162987
TI  - RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg
      case-cohort, Athero-Express and CARDIoGRAM studies.
AB  - BACKGROUND: The chemokine RANTES (regulated on activation, normal T-cell
      expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular
      disease in mice, whereas less is known in humans. We hypothesised that its
      relevance for atherosclerosis should be reflected by associations between CCL5
      gene variants, RANTES serum concentrations and protein levels in atherosclerotic
      plaques and risk for coronary events. METHODS AND FINDINGS: We conducted a case
      cohort study within the population-based MONICA/KORA Augsburg studies. Baseline
      RANTES serum levels were measured in 363 individuals with incident coronary
      events and 1,908 non-cases (mean follow-up: 10.2+/-4.8 years). Cox proportional
      hazard models adjusting for age, sex, body mass index, metabolic factors and
      lifestyle factors revealed no significant association between RANTES and incident
      coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42]
      and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no
      common haplotype showed significant associations with coronary events. Also in
      the CARDIoGRAM study (>22,000 cases, >60,000 controls), none of these CCL5 SNPs
      was significantly associated with coronary artery disease. In the prospective
      Athero-Express biobank study, RANTES plaque levels were measured in 606
      atherosclerotic lesions from patients who underwent carotid endarterectomy.
      RANTES content in atherosclerotic plaques was positively associated with
      macrophage infiltration and inversely associated with plaque calcification.
      However, there was no significant association between RANTES content in plaques
      and risk for coronary events (mean follow-up 2.8+/-0.8 years). CONCLUSIONS: High
      RANTES plaque levels were associated with an unstable plaque phenotype. However,
      the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes
      and (iii) RANTES content in carotid plaques and either coronary artery disease or
      incident coronary events in our cohorts suggests that RANTES may not be a novel
      coronary risk biomarker. However, the potential relevance of RANTES levels in
      platelet-poor plasma needs to be investigated in further studies.

PMID- 22162991
TI  - Mining relational paths in integrated biomedical data.
AB  - Much life science and biology research requires an understanding of complex
      relationships between biological entities (genes, compounds, pathways, diseases,
      and so on). There is a wealth of data on such relationships in publicly available
      datasets and publications, but these sources are overlapped and distributed so
      that finding pertinent relational data is increasingly difficult. Whilst most
      public datasets have associated tools for searching, there is a lack of searching
      methods that can cross data sources and that in particular search not only based
      on the biological entities themselves but also on the relationships between them.
      In this paper, we demonstrate how graph-theoretic algorithms for mining
      relational paths can be used together with a previous integrative data resource
      we developed called Chem2Bio2RDF to extract new biological insights about the
      relationships between such entities. In particular, we use these methods to
      investigate the genetic basis of side-effects of thiazolinedione drugs, and in
      particular make a hypothesis for the recently discovered cardiac side-effects of
      Rosiglitazone (Avandia) and a prediction for Pioglitazone which is backed up by
      recent clinical studies.

PMID- 22162992
TI  - Pharmacogenetic & pharmacokinetic biomarker for efavirenz based ARV and
      rifampicin based anti-TB drug induced liver injury in TB-HIV infected patients.
AB  - BACKGROUND: Implication of pharmacogenetic variations and efavirenz
      pharmacokinetics in concomitant efavirenz based antiviral therapy and anti
      tubercular drug induced liver injury (DILI) has not been yet studied. We
      performed a prospective case-control association study to identify the incidence,
      pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular
      and antiretroviral drugs induced liver injury (DILI) in HIV and tuberculosis (TB)
      co-infected patients. METHODS AND FINDINGS: Newly diagnosed treatment naive TB
      HIV co-infected patients (n = 353) were enrolled to receive efavirenz based ART
      and rifampicin based anti-TB therapy, and assessed clinically and biochemically
      for DILI up to 56 weeks. Quantification of plasma efavirenz and 8
      hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7
      and SLCO1B1 genes were done. The incidence of DILI and identification of
      predictors was evaluated using survival analysis and the Cox Proportional Hazards
      Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of
      severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant
      association of DILI with being of the female sex (p = 0.001), higher plasma
      efavirenz level (p = 0.009), efavirenz/8-hydroxyefavirenz ratio (p = 0.036),
      baseline AST (p = 0.022), ALT (p = 0.014), lower hemoglobin (p = 0.008), and
      serum albumin (p = 0.007), NAT2 slow-acetylator genotype (p = 0.039) and ABCB1
      3435TT genotype (p = 0.001). CONCLUSION: We report high incidence of anti
      tubercular and antiretroviral DILI in Ethiopian patients. Between patient
      variability in systemic efavirenz exposure and pharmacogenetic variations in
      NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co
      infected patients. Close monitoring of plasma efavirenz level and liver enzymes
      during early therapy and/or genotyping practice in HIV clinics is recommended for
      early identification of patients at risk of DILI.

PMID- 22162994
TI  - Rohlin distance and the evolution of influenza A virus: weak attractors and
      precursors.
AB  - The evolution of the hemagglutinin amino acids sequences of Influenza A virus is
      studied by a method based on an informational metrics, originally introduced by
      Rohlin for partitions in abstract probability spaces. This metrics does not
      require any previous functional or syntactic knowledge about the sequences and it
      is sensitive to the correlated variations in the characters disposition. Its
      efficiency is improved by algorithmic tools, designed to enhance the detection of
      the novelty and to reduce the noise of useless mutations. We focus on the USA
      data from 1993/94 to 2010/2011 for A/H3N2 and on USA data from 2006/07 to
      2010/2011 for A/H1N1. We show that the clusterization of the distance matrix
      gives strong evidence to a structure of domains in the sequence space, acting as
      weak attractors for the evolution, in very good agreement with the
      epidemiological history of the virus. The structure proves very robust with
      respect to the variations of the clusterization parameters, and extremely
      coherent when restricting the observation window. The results suggest an
      efficient strategy in the vaccine forecast, based on the presence of "precursors"
      (or "buds") populating the most recent attractor.

PMID- 22162993
TI  - Pregnant women's access to PMTCT and ART services in South Africa and
      implications for universal antiretroviral treatment.
AB  - OBJECTIVES: We describe pregnant womens' access to PMTCT and HAART services and
      associated birth outcomes in South Africa. METHODS: Women recuperating in
      postnatal wards of a referral hospital participated in an evaluation during
      February-May 2010 during which their maternity records were examined to describe
      their access to VCT, CD4 Counts, dual ART or HAART during pregnancy. RESULTS: Of
      the 1609 women who participated in this evaluation, 39% (95%CI36.7-41.5%) tested
      HIV-positive during their pregnancy. Of the HIV-positive women 2.9% did not have
      a CD4 count done and an additional 31.3% did not receive their CD4 results. The
      majority (96.8%) of the HIV-positive women commenced dual ART at their first
      antenatal visit independent of their CD4 result. During February-May 2010, 48.0%
      of the women who had a CD4 result were eligible for HAART (CD4<200 cells/mm(3))
      and 29.1% of these initiated HAART during pregnancy. Under the current South
      African PMTCT guidelines 71.1% (95%CI66.4-75.4%) of HIV positive pregnant women
      could be eligible for HAART (CD4<350 cells/mm(3)). There were significantly more
      preterm births among HIV-positive women (p = 0.01) and women who received HAART
      were no more at risk of preterm deliveries (AOR 0.73;95%CI0.39-1.36;p = 0.2) as
      compared to women who received dual ART. Nine (2.4%; 95%CI1.1-4.5%) HIV exposed
      infants were confirmed HIV infected at birth. The in-utero transmission rate was
      highest among women who required HAART but did not initiate treatment (8.5%)
      compared to 2.7% and 0.4% among women who received HAART and women who were not
      eligible for HAART and received PMTCT prophylaxis respectively. CONCLUSION: In
      this urban South African community the antenatal HIV prevalence remains high
      (39%) and timeous access to CD4 results during pregnancy is limited. Under the
      current South African guidelines, and assuming that access to CD4 results has
      improved, more than 70% of HIV-positive pregnant women in this community would be
      requiring HAART.

PMID- 22162995
TI  - Accurate genome relative abundance estimation based on shotgun metagenomic reads.
AB  - Accurate estimation of microbial community composition based on metagenomic
      sequencing data is fundamental for subsequent metagenomics analysis. Prevalent
      estimation methods are mainly based on directly summarizing alignment results or
      its variants; often result in biased and/or unstable estimates. We have developed
      a unified probabilistic framework (named GRAMMy) by explicitly modeling read
      assignment ambiguities, genome size biases and read distributions along the
      genomes. Maximum likelihood method is employed to compute Genome Relative
      Abundance of microbial communities using the Mixture Model theory (GRAMMy).
      GRAMMy has been demonstrated to give estimates that are accurate and robust
      across both simulated and real read benchmark datasets. We applied GRAMMy to a
      collection of 34 metagenomic read sets from four metagenomics projects and
      identified 99 frequent species (minimally 0.5% abundant in at least 50% of the
      data-sets) in the human gut samples. Our results show substantial improvements
      over previous studies, such as adjusting the over-estimated abundance for
      Bacteroides species for human gut samples, by providing a new reference-based
      strategy for metagenomic sample comparisons. GRAMMy can be used flexibly with
      many read assignment tools (mapping, alignment or composition-based) even with
      low-sensitivity mapping results from huge short-read datasets. It will be
      increasingly useful as an accurate and robust tool for abundance estimation with
      the growing size of read sets and the expanding database of reference genomes.

PMID- 22162996
TI  - A human monoclonal antibody with neutralizing activity against highly divergent
      influenza subtypes.
AB  - The interest in broad-range anti-influenza A monoclonal antibodies (mAbs) has
      recently been strengthened by the identification of anti-hemagglutinin (HA) mAbs
      endowed with heterosubtypic neutralizing activity to be used in the design of
      "universal" prophylactic or therapeutic tools. However, the majority of the
      single mAbs described to date do not bind and neutralize viral isolates belonging
      to highly divergent subtypes clustering into the two different HA-based influenza
      phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and
      H9 and the group 2 including, among others, H3 subtype. Here, we describe a human
      mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates
      belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes
      and several isolates belonging to group 2, including H3N2 isolates from the first
      period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing
      isolates belonging to subtypes responsible of all the reported pandemics, as well
      as other subtypes with pandemic potential. The region recognized by PN-SIA28 has
      been identified on the stem region of HA and includes residues highly conserved
      among the different influenza subtypes. A deep characterization of PN-SIA28
      features may represent a useful help in the improvement of available anti
      influenza therapeutic strategies and can provide new tools for the development of
      universal vaccinal strategies.

PMID- 22162997
TI  - An open source simulation model for soil and sediment bioturbation.
AB  - Bioturbation is one of the most widespread forms of ecological engineering and
      has significant implications for the structure and functioning of ecosystems, yet
      our understanding of the processes involved in biotic mixing remains incomplete.
      One reason is that, despite their value and utility, most mathematical models
      currently applied to bioturbation data tend to neglect aspects of the natural
      complexity of bioturbation in favour of mathematical simplicity. At the same
      time, the abstract nature of these approaches limits the application of such
      models to a limited range of users. Here, we contend that a movement towards
      process-based modelling can improve both the representation of the mechanistic
      basis of bioturbation and the intuitiveness of modelling approaches. In support
      of this initiative, we present an open source modelling framework that explicitly
      simulates particle displacement and a worked example to facilitate application
      and further development. The framework combines the advantages of rule-based
      lattice models with the application of parameterisable probability density
      functions to generate mixing on the lattice. Model parameters can be fitted by
      experimental data and describe particle displacement at the spatial and temporal
      scales at which bioturbation data is routinely collected. By using the same model
      structure across species, but generating species-specific parameters, a generic
      understanding of species-specific bioturbation behaviour can be achieved. An
      application to a case study and comparison with a commonly used model attest the
      predictive power of the approach.

PMID- 22162998
TI  - Mountain refugia play a role in soil arthropod speciation on Madagascar: a case
      study of the endemic giant fire-millipede genus Aphistogoniulus.
AB  - To elucidate the speciation mechanisms prevalent within hotspots of biodiversity,
      and the evolutionary processes behind the rise of their species-rich and endemic
      biota, we investigated the phylogeny of the giant fire-millipede genus
      Aphistogoniulus Silvestri, 1897, a Malagasy endemic. This study is the first
      comprehensive (molecular and morphological) phylogenetic study focusing on
      millipede (class Diplopoda) speciation on Madagascar. The morphological analysis
      is based on 35 morphological characters and incorporates ten described as well as
      two newly described species (A. rubrodorsalisn. sp. and A. jeekelin. sp.) of
      Aphistogoniulus. The molecular analysis is based on both mitochondrial (COI and
      16S), and nuclear genes (complete 18S rDNA), together comprised of 3031 base
      pairs, which were successfully sequenced for 31 individual specimens and eight
      species of Aphistogoniulus. In addition to the null-model (speciation by
      distance), two diversification models, mountain refugia and ecotone shift, were
      discovered to play a role in the speciation of soil arthropods on Madagascar.
      Mountain refugia were important in the speciation of the A. cowani clade, with
      three species occurring in the Andringitra and Ranomafana Mountains in the
      southeast (A. cowani), the Ambohijanahary and Ambohitantely Mountains in the mid
      west (A. sanguineus), and the Marojejy Mountain in the northeast (A.
      rubrodorsalisn. sp.). An ecotone shift from the eastern rainforest to the unique
      subarid spiny forest of Mahavelo was discovered in the A. vampyrus-A. aridus
      species-pair. In the monophyletic A. diabolicus clade, evidence for divergent
      evolution of sexual morphology was detected: species with greatly enlarged
      gonopods are sister-taxa to species with normal sized gonopods. Among the large
      bodied Spirobolida genera of Madagascar, Colossobolus and Sanguinobolus were
      found to be close sister-genera to Aphistogoniulus. Forest destruction has caused
      forest corridors between populations to disappear, which might limit the possible
      resolution of biogeographic analyses on Madagascar.

PMID- 22162999
TI  - SAF-A forms a complex with BRG1 and both components are required for RNA
      polymerase II mediated transcription.
AB  - BACKGROUND: Scaffold attachment factor A (SAF-A) participates in the regulation
      of gene expression by organizing chromatin into transcriptionally active domains
      and by interacting directly with RNA polymerase II. METHODOLOGY: Here we use co
      localization, co-immunoprecipitation (co-IP) and in situ proximity ligation assay
      (PLA) to identify Brahma Related Gene 1 (BRG1), the ATP-driven motor of the human
      SWI-SNF chromatin remodeling complex, as another SAF-A interaction partner in
      mouse embryonic stem (mES) cells. We also employ RNA interference to investigate
      functional aspects of the SAF-A/BRG1 interaction. PRINCIPAL FINDINGS: We find
      that endogenous SAF-A protein interacts with endogenous BRG1 protein in mES
      cells, and that the interaction does not solely depend on the presence of mRNA.
      Moreover the interaction remains intact when cells are induced to differentiate.
      Functional analyses reveal that dual depletion of SAF-A and BRG1 abolishes global
      transcription by RNA polymerase II, while the nucleolar RNA polymerase I
      transcription machinery remains unaffected. CONCLUSIONS: We demonstrate that SAF
      A interacts with BRG1 and that both components are required for RNA Polymerase II
      Mediated Transcription.

PMID- 22163000
TI  - Cannabidiol reduces intestinal inflammation through the control of neuroimmune
      axis.
AB  - Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the
      gut; EGC proliferate and release neurotrophins, growth factors, and pro
      inflammatory cytokines which, in turn, may amplify the immune response,
      representing a very important link between the nervous and immune systems in the
      intestine. Cannabidiol (CBD) is an interesting compound because of its ability to
      control reactive gliosis in the CNS, without any unwanted psychotropic effects.
      Therefore the rationale of our study was to investigate the effect of CBD on
      intestinal biopsies from patients with ulcerative colitis (UC) and from
      intestinal segments of mice with LPS-induced intestinal inflammation. CBD
      markedly counteracted reactive enteric gliosis in LPS-mice trough the massive
      reduction of astroglial signalling neurotrophin S100B. Histological, biochemical
      and immunohistochemical data demonstrated that S100B decrease was associated with
      a considerable decrease in mast cell and macrophages in the intestine of LPS
      treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD
      reduced TNF-alpha expression and the presence of cleaved caspase-3. Similar
      results were obtained in ex vivo cultured human derived colonic biopsies. In
      biopsies of UC patients, both during active inflammation and in remission
      stimulated with LPS+INF-gamma, an increased glial cell activation and intestinal
      damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in
      the human biopsies confirming its well documented effect in septic mice. The
      activity of CBD is, at least partly, mediated via the selective PPAR-gamma
      receptor pathway. CBD targets enteric reactive gliosis, counteracts the
      inflammatory environment induced by LPS in mice and in human colonic cultures
      derived from UC patients. These actions lead to a reduction of intestinal damage
      mediated by PPARgamma receptor pathway. Our results therefore indicate that CBD
      indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.

PMID- 22163001
TI  - Evidence for widespread genomic methylation in the migratory locust, Locusta
      migratoria (Orthoptera: Acrididae).
AB  - The importance of DNA methylation in mammalian and plant systems is well
      established. In recent years there has been renewed interest in DNA methylation
      in insects. Accumulating evidence, both from mammals and insects, points towards
      an emerging role for DNA methylation in the regulation of phenotypic plasticity.
      The migratory locust (Locusta migratoria) is a model organism for the study of
      phenotypic plasticity. Despite this, there is little information available about
      the degree to which the genome is methylated in this species and genes encoding
      methylation machinery have not been previously identified. We therefore undertook
      an initial investigation to establish the presence of a functional DNA
      methylation system in L. migratoria. We found that the migratory locust possesses
      genes that putatively encode methylation machinery (DNA methyltransferases and a
      methyl-binding domain protein) and exhibits genomic methylation, some of which
      appears to be localised to repetitive regions of the genome. We have also
      identified a distinct group of genes within the L. migratoria genome that appear
      to have been historically methylated and show some possible functional
      differentiation. These results will facilitate more detailed research into the
      functional significance of DNA methylation in locusts.

PMID- 22163002
TI  - Structural position correlation analysis (SPCA) for protein family.
AB  - BACKGROUND: The proteins in a family, which perform the similar biological
      functions, may have very different amino acid composition, but they must share
      the similar 3D structures, and keep a stable central region. In the conservative
      structure region similar biological functions are performed by two or three
      catalytic residues with the collaboration of several functional residues at key
      positions. Communication signals are conducted in a position network, adjusting
      the biological functions in the protein family. METHODOLOGY: A computational
      approach, namely structural position correlation analysis (SPCA), is developed to
      analyze the correlation relationship between structural segments (or positions).
      The basic hypothesis of SPCA is that in a protein family the structural
      conservation is more important than the sequence conservation, and the local
      structural changes may contain information of biology functional evolution. A
      standard protein P(0) is defined in a protein family, which consists of the most
      frequent amino acids and takes the average structure of the protein family. The
      foundational variables of SPCA is the structural position displacements between
      the standard protein P(0) and individual proteins P(i) of the family. The
      structural positions are organized as segments, which are the stable units in
      structural displacements of the protein family. The biological function
      differences of protein members are determined by the position structural
      displacements of individual protein P(i) to the standard protein P(0).
      Correlation analysis is used to analyze the communication network among segments.
      CONCLUSIONS: The structural position correlation analysis (SPCA) is able to find
      the correlation relationship among the structural segments (or positions) in a
      protein family, which cannot be detected by the amino acid sequence and frequency
      based methods. The functional communication network among the structural segments
      (or positions) in protein family, revealed by SPCA approach, well illustrate the
      distantly allosteric interactions, and contains valuable information for protein
      engineering study.

PMID- 22163003
TI  - Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low
      malignant potential and low grade ovarian serous tumours.
AB  - Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains
      unknown. Histological and genetic evidence has led to the proposal that low grade
      ovarian serous carcinomas (LGOSC) have a different etiology than high grade
      carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP).
      Common regions of chromosome (chr) 3 loss have been observed in all types of
      serous ovarian tumours, including benign, suggesting that these regions contain
      genes important in the development of all ovarian serous carcinomas. A high
      density genome-wide genotyping bead array technology, which assayed >600,000
      markers, was applied to a panel of serous benign and LMP tumours and a small set
      of LGOSC, to characterize somatic events associated with the most indolent forms
      of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and
      BRAF mutations. An increasing frequency of genomic anomalies was observed with
      pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and
      10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all
      tumour types. Runs of homozygosity were most commonly observed on chr3, with the
      3p12-p11 candidate tumour suppressor region the most frequently homozygous region
      in the genome. An LMP harboured a homozygous deletion on chr6 which created a
      GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types.
      Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS
      mutation positive LMP cases displayed significantly more chromosomal aberrations
      than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of
      12p, which harbours the KRAS gene, was particularly evident. A pathology review
      reclassified all TP53-mutation positive LGOSC cases, some of which acquired a
      HGOSC status. Taken together, our results support the view that LGOSC could arise
      from serous benign and LMP tumours, but does not exclude the possibility that
      HGOSC may derive from LMP tumours.

PMID- 22163005
TI  - Molecular phylogeny of the Acanthocephala (class Palaeacanthocephala) with a
      paraphyletic assemblage of the orders Polymorphida and Echinorhynchida.
AB  - Acanthocephalans are attractive candidates as model organisms for studying the
      ecology and co-evolutionary history of parasitic life cycles in the marine
      ecosystem. Adding to earlier molecular analyses of this taxon, a total of 36
      acanthocephalans belonging to the classes Archiacanthocephala (3 species),
      Eoacanthocephala (3 species), Palaeacanthocephala (29 species),
      Polyacanthocephala (1 species) and Rotifera as outgroup (3 species) were analyzed
      by using Bayesian Inference and Maximum Likelihood analyses of nuclear 18S rDNA
      sequence. This data set included three re-collected and six newly collected taxa,
      Bolbosoma vasculosum from Lepturacanthus savala, Filisoma rizalinum from
      Scatophagus argus, Rhadinorhynchus pristis from Gempylus serpens, R. lintoni from
      Selar crumenophthalmus, Serrasentis sagittifer from Johnius coitor, and
      Southwellina hispida from Epinephelus coioides, representing 5 new host and 3 new
      locality records. The resulting trees suggest a paraphyletic arrangement of the
      Echinorhynchida and Polymorphida inside the Palaeacanthocephala. This questions
      the placement of the genera Serrasentis and Gorgorhynchoides within the
      Echinorhynchida and not the Polymorphida, necessitating further insights into the
      systematic position of these taxa based on morphology.

PMID- 22163004
TI  - Correlation of inter-locus polyglutamine toxicity with CAG*CTG triplet repeat
      expandability and flanking genomic DNA GC content.
AB  - Dynamic expansions of toxic polyglutamine (polyQ)-encoding CAG repeats in
      ubiquitously expressed, but otherwise unrelated, genes cause a number of late
      onset progressive neurodegenerative disorders, including Huntington disease and
      the spinocerebellar ataxias. As polyQ toxicity in these disorders increases with
      repeat length, the intergenerational expansion of unstable CAG repeats leads to
      anticipation, an earlier age-at-onset in successive generations. Crucially,
      disease associated alleles are also somatically unstable and continue to expand
      throughout the lifetime of the individual. Interestingly, the inherited polyQ
      length mediating a specific age-at-onset of symptoms varies markedly between
      disorders. It is widely assumed that these inter-locus differences in polyQ
      toxicity are mediated by protein context effects. Previously, we demonstrated
      that the tendency of expanded CAG*CTG repeats to undergo further
      intergenerational expansion (their 'expandability') also differs between
      disorders and these effects are strongly correlated with the GC content of the
      genomic flanking DNA. Here we show that the inter-locus toxicity of the expanded
      polyQ tracts of these disorders also correlates with both the expandability of
      the underlying CAG repeat and the GC content of the genomic DNA flanking
      sequences. Inter-locus polyQ toxicity does not correlate with properties of the
      mRNA or protein sequences, with polyQ location within the gene or protein, or
      steady state transcript levels in the brain. These data suggest that the observed
      inter-locus differences in polyQ toxicity are not mediated solely by protein
      context effects, but that genomic context is also important, an effect that may
      be mediated by modifying the rate at which somatic expansion of the DNA delivers
      proteins to their cytotoxic state.

PMID- 22163006
TI  - Concanavalin A/IFN-gamma triggers autophagy-related necrotic hepatocyte death
      through IRGM1-mediated lysosomal membrane disruption.
AB  - Interferon-gamma (IFN-gamma), a potent Th1 cytokine with multiple biological
      functions, can induce autophagy to enhance the clearance of the invading
      microorganism or cause cell death. We have reported that Concanavalin A (Con A)
      can cause autophagic cell death in hepatocytes and induce both T cell-dependent
      and -independent acute hepatitis in immunocompetent and immunodeficient mice,
      respectively. Although IFN-gamma is known to enhance liver injury in Con A
      induced hepatitis, its role in autophagy-related hepatocyte death is not clear.
      In this study we report that IFN-gamma can enhance Con A-induced autophagic flux
      and cell death in hepatoma cell lines. A necrotic cell death with increased
      lysosomal membrane permeabilization (LMP) is observed in Con A-treated hepatoma
      cells in the presence of IFN-gamma. Cathepsin B and L were released from
      lysosomes to cause cell death. Furthermore, IFN-gamma induces immunity related
      GTPase family M member 1(IRGM1) translocation to lysosomes and prolongs its
      activity in Con A-treated hepatoma cells. Knockdown of IRGM1 inhibits the IFN
      gamma/Con A-induced LMP change and cell death. Furthermore, IFN-gamma(-/-) mice
      are resistant to Con A-induced autophagy-associated necrotic hepatocyte death. We
      conclude that IFN-gamma enhances Con A-induced autophagic flux and causes an
      IRGM1-dependent lysosome-mediated necrotic cell death in hepatocytes.

PMID- 22163007
TI  - MicroRNA-1 and -133 increase arrhythmogenesis in heart failure by dissociating
      phosphatase activity from RyR2 complex.
AB  - In heart failure (HF), arrhythmogenic spontaneous sarcoplasmic reticulum (SR)
      Ca(2+) release and afterdepolarizations in cardiac myocytes have been linked to
      abnormally high activity of ryanodine receptors (RyR2s) associated with enhanced
      phosphorylation of the channel. However, the specific molecular mechanisms
      underlying RyR2 hyperphosphorylation in HF remain poorly understood. The
      objective of the current study was to test the hypothesis that the enhanced
      expression of muscle-specific microRNAs (miRNAs) underlies the HF-related
      alterations in RyR2 phosphorylation in ventricular myocytes by targeting
      phosphatase activity localized to the RyR2. We studied hearts isolated from
      canines with chronic HF exhibiting increased left ventricular (LV) dimensions and
      decreased LV contractility. qRT-PCR revealed that the levels of miR-1 and miR
      133, the most abundant muscle-specific miRNAs, were significantly increased in HF
      myocytes compared with controls (2- and 1.6-fold, respectively). Western blot
      analyses demonstrated that expression levels of the protein phosphatase 2A (PP2A)
      catalytic and regulatory subunits, which are putative targets of miR-133 and miR
      1, were decreased in HF cells. PP2A catalytic subunit mRNAs were validated as
      targets of miR-133 by using luciferase reporter assays. Pharmacological
      inhibition of phosphatase activity increased the frequency of diastolic Ca(2+)
      waves and afterdepolarizations in control myocytes. The decreased PP2A activity
      observed in HF was accompanied by enhanced Ca(2+)/calmodulin-dependent protein
      kinase (CaMKII)-mediated phosphorylation of RyR2 at sites Ser-2814 and Ser-2030
      and increased frequency of diastolic Ca(2+) waves and afterdepolarizations in HF
      myocytes compared with controls. In HF myocytes, CaMKII inhibitory peptide
      normalized the frequency of pro-arrhythmic spontaneous diastolic Ca(2+) waves.
      These findings suggest that altered levels of major muscle-specific miRNAs
      contribute to abnormal RyR2 function in HF by depressing phosphatase activity
      localized to the channel, which in turn, leads to the excessive phosphorylation
      of RyR2s, abnormal Ca(2+) cycling, and increased propensity to arrhythmogenesis.

PMID- 22163009
TI  - Mislocalization of visual stimuli: independent effects of static and dynamic
      attention.
AB  - Shifts of visual attention cause systematic distortions of the perceived
      locations of visual objects around the focus of attention. In the attention
      repulsion effect, the perceived location of a visual target is shifted away from
      an attention-attracting cue when the cue is presented before the target. Recently
      it has been found that, if the visual cue is presented after the target, the
      perceived location of the target shifts toward the location of the following cue.
      One unanswered question is whether a single mechanism underlies both attentional
      repulsion and attraction effects. We presented participants with two disks at
      diagonal locations as visual cues and two vertical lines as targets. Participants
      were asked to perform a forced-choice task to judge targets' positions. The
      present study examined whether the magnitude of the repulsion effect and the
      attraction effect would differ (Experiment 1), whether the two effects would
      interact (Experiment 2), and whether the location or the dynamic shift of
      attentional focus would determine the distortions effects (Experiment 3). The
      results showed that the effect size of the attraction effect was slightly larger
      than the repulsion effect and the preceding and following cues have independent
      influences on the perceived positions. The repulsion effect was caused by the
      location of attnetion and the attraction effect was due to the dynamic shift of
      attentional focus, suggesting that the underlying mechanisms for the
      retrospective attraction effect might be different from those for the repulsion
      effect.

PMID- 22163008
TI  - Methicillin-susceptible ST398 Staphylococcus aureus responsible for bloodstream
      infections: an emerging human-adapted subclone?
AB  - In the course of an annual 3-month bloodstream infections (BSI) survey conducted
      during a four-year period in 31 healthcare institutions located in three
      noncontiguous French regions, we report 18 ST398 Staphylococcus aureus BSI. ST398
      BSI incidence showed a seven-fold increase during the study period (0.002 per
      1,000 patient days in 2007 vs. 0.014 in 2010). ST398 BSI isolates differed from
      the pig-borne multiresistant clone: 17/18 BSI isolates were methicillin
      susceptible and none was of t011, t034 or t108 pig-borne spa-types. ST398 BSI
      isolates had homogenous resistance patterns (15/18 with only Ery(r)) and
      prophagic content (all harboured the hlb-converting Sau3int phage). The
      clustering of BSI and pig-borne isolates by spa-typing and MLVA, the occurrence
      of Sau3int phage in BSI isolates and the lack of this phage in pig-borne isolates
      suggest that the emergence of BSI isolates could have arisen from horizontal
      transfer, at least of the Sau3int phage, in genetically diverse MSSA ST398
      isolates. The acquisition of the phage likely plays a role in the increasing
      ability of the lysogenic ST398 isolates to colonize human. The mode of
      acquisition of the non pig-borne ST398 isolates by our 18 patients remains
      unclear. ST398 BSI were diagnosed in patients lacking livestock exposure and were
      significantly associated with digestive portals of entry (3/18 [16.7%] for ST398
      vs. 19/767 [2.5%] for non ST398 BSI; p = .012). This raises the question of
      possible foodborne human infections. We suggest the need for active surveillance
      to study and control the spread of this human-adapted subclone increasingly
      isolated in the hospital setting.

PMID- 22163011
TI  - AcrB trimer stability and efflux activity, insight from mutagenesis studies.
AB  - The multidrug transporter AcrB in Escherichia coli exists and functions as a homo
      trimer. The assembly process of obligate membrane protein oligomers, including
      AcrB, remains poorly understood. In a previous study, we have shown that
      individual AcrB subunit is capable of folding independently, suggesting that
      trimerization of AcrB follows a three-stage pathway in which monomers first fold,
      and then assemble. Here we destabilized the AcrB trimer through mutating a single
      Pro (P223) in the protruding loop of AcrB, which drastically reduced the protein
      activity. We replaced P223 separately with five residues, including Ala, Val,
      Tyr, Asn, and Gly, and found that AcrB(P223G) was the least active. Detailed
      characterization of AcrB(P223G) revealed that the protein existed as a well
      folded monomer after purification, but formed a trimer in vivo. The function of
      the mutant could be partly restored through strengthening the stability of the
      trimer using an inter-subunit disulfide bond. Our results also suggested that the
      protruding loop is well structured during AcrB assembly with P223 served as a
      "wedge" close to the tip to stabilize the AcrB trimer structure. When this wedge
      is disrupted, the stability of the trimer is reduced, accompanied by a decrease
      of drug efflux activity.

PMID- 22163010
TI  - Mannose receptor (MR) engagement by mesothelin GPI anchor polarizes tumor
      associated macrophages and is blocked by anti-MR human recombinant antibody.
AB  - Tumor-infiltrating macrophages respond to microenvironmental signals by
      developing a tumor-associated phenotype characterized by high expression of
      mannose receptor (MR, CD206). Antibody cross-linking of CD206 triggers anergy in
      dendritic cells and CD206 engagement by tumoral mucins activates an immune
      suppressive phenotype in tumor-associated macrophages (TAMs). Many tumor antigens
      are heavily glycosylated, such as tumoral mucins, and/or attached to tumor cells
      by mannose residue-containing glycolipids (GPI anchors), as for example
      mesothelin and the family of carcinoembryonic antigen (CEA). However, the binding
      to mannose receptor of soluble tumor antigen GPI anchors via mannose residues has
      not been systematically studied. To address this question, we analyzed the
      binding of tumor-released mesothelin to ascites-infiltrating macrophages from
      ovarian cancer patients. We also modeled functional interactions between
      macrophages and soluble mesothelin using an in vitro system of co-culture in
      transwells of healthy donor macrophages with human ovarian cancer cell lines. We
      found that soluble mesothelin bound to human macrophages and that the binding
      depended on the presence of GPI anchor and of mannose receptor. We next
      challenged the system with antibodies directed against the mannose receptor
      domain 4 (CDR4-MR). We isolated three novel anti-CDR4-MR human recombinant
      antibodies (scFv) using a yeast-display library of human scFv. Anti-CDR4-MR scFv
      #G11 could block mesothelin binding to macrophages and prevent tumor-induced
      phenotype polarization of CD206(low) macrophages towards TAMs. Our findings
      indicate that tumor-released mesothelin is linked to GPI anchor, engages
      macrophage mannose receptor, and contributes to macrophage polarization towards
      TAMs. We propose that compounds able to block tumor antigen GPI anchor/CD206
      interactions, such as our novel anti-CRD4-MR scFv, could prevent tumor-induced
      TAM polarization and have therapeutic potential against ovarian cancer, through
      polarization control of tumor-infiltrating innate immune cells.

PMID- 22163012
TI  - Response of soil respiration to soil temperature and moisture in a 50-year-old
      oriental arborvitae plantation in China.
AB  - China possesses large areas of plantation forests which take up great quantities
      of carbon. However, studies on soil respiration in these plantation forests are
      rather scarce and their soil carbon flux remains an uncertainty. In this study,
      we used an automatic chamber system to measure soil surface flux of a 50-year-old
      mature plantation of Platycladus orientalis at Jiufeng Mountain, Beijing, China.
      Mean daily soil respiration rates (R(s)) ranged from 0.09 to 4.87 umol CO(2) m(
      2) s(-1), with the highest values observed in August and the lowest in the winter
      months. A logistic model gave the best fit to the relationship between hourly
      R(s) and soil temperature (T(s)), explaining 82% of the variation in R(s) over
      the annual cycle. The annual total of soil respiration estimated from the
      logistic model was 645+/-5 g C m(-2) year(-1). The performance of the logistic
      model was poorest during periods of high soil temperature or low soil volumetric
      water content (VWC), which limits the model's ability to predict the seasonal
      dynamics of R(s). The logistic model will potentially overestimate R(s) at high
      T(s) and low VWC. Seasonally, R(s) increased significantly and linearly with
      increasing VWC in May and July, in which VWC was low. In the months from August
      to November, inclusive, in which VWC was not limiting, R(s) showed a positively
      exponential relationship with T(s). The seasonal sensitivity of soil respiration
      to T(s) (Q(10)) ranged from 0.76 in May to 4.38 in October. It was suggested that
      soil temperature was the main determinant of soil respiration when soil water was
      not limiting.

PMID- 22163013
TI  - Quantifying the spatial ecology of wide-ranging marine species in the Gulf of
      California: implications for marine conservation planning.
AB  - There is growing interest in systematic establishment of marine protected area
      (MPA) networks and representative conservation sites. This movement toward
      networks of no-take zones requires that reserves are deliberately and adequately
      spaced for connectivity. Here, we test the network functionality of an
      ecoregional assessment configuration of marine conservation areas by evaluating
      the habitat protection and connectivity offered to wide-ranging fauna in the Gulf
      of California (GOC, Mexico). We first use expert opinion to identify
      representative species of wide-ranging fauna of the GOC. These include leopard
      grouper, hammerhead sharks, California brown pelicans and green sea turtles.
      Analyzing habitat models with both structural and functional connectivity
      indexes, our results indicate that the configuration includes large proportions
      of biologically important habitat for the four species considered (25-40%),
      particularly, the best quality habitats (46-57%). Our results also show that
      connectivity levels offered by the conservation area design for these four
      species may be similar to connectivity levels offered by the entire Gulf of
      California, thus indicating that connectivity offered by the areas may resemble
      natural connectivity. The selected focal species comprise different life
      histories among marine or marine-related vertebrates and are associated with
      those habitats holding the most biodiversity values (i.e. coastal habitats); our
      results thus suggest that the proposed configuration may function as a network
      for connectivity and may adequately represent the marine megafauna in the GOC,
      including the potential connectivity among habitat patches. This work highlights
      the range of approaches that can be used to quantify habitat protection and
      connectivity for wide-ranging marine species in marine reserve networks.

PMID- 22163014
TI  - Long-distance translocation of protein during morphogenesis of the fruiting body
      in the filamentous fungus, Agaricus bisporus.
AB  - Commercial cultivation of the mushroom fungus, Agaricus bisporus, utilizes a
      substrate consisting of a lower layer of compost and upper layer of peat.
      Typically, the two layers are seeded with individual mycelial inoculants
      representing a single genotype of A. bisporus. Studies aimed at examining the
      potential of this fungal species as a heterologous protein expression system have
      revealed unexpected contributions of the mycelial inoculants in the morphogenesis
      of the fruiting body. These contributions were elucidated using a dual-inoculant
      method whereby the two layers were differientially inoculated with transgenic
      beta-glucuronidase (GUS) and wild-type (WT) lines. Surprisingly, use of a
      transgenic GUS line in the lower substrate and a WT line in the upper substrate
      yielded fruiting bodies expressing GUS activity while lacking the GUS transgene.
      Results of PCR and RT-PCR analyses for the GUS transgene and RNA transcript,
      respectively, suggested translocation of the GUS protein from the transgenic
      mycelium colonizing the lower layer into the fruiting body that developed
      exclusively from WT mycelium colonizing the upper layer. Effective translocation
      of the GUS protein depended on the use of a transgenic line in the lower layer in
      which the GUS gene was controlled by a vegetative mycelium-active promoter
      (laccase 2 and beta-actin), rather than a fruiting body-active promoter
      (hydrophobin A). GUS-expressing fruiting bodies lacking the GUS gene had a
      bonafide WT genotype, confirmed by the absence of stably inherited GUS and
      hygromycin phosphotransferase selectable marker activities in their derived
      basidiospores and mycelial tissue cultures. Differientially inoculating the two
      substrate layers with individual lines carrying the GUS gene controlled by
      different tissue-preferred promoters resulted in up to a ~3.5-fold increase in
      GUS activity over that obtained with a single inoculant. Our findings support the
      existence of a previously undescribed phenomenon of long-distance protein
      translocation in A. bisporus that has potential application in recombinant
      protein expression and biotechnological approaches for crop improvement.

PMID- 22163015
TI  - Corneal alterations during combined therapy with cyclodextrin/allopregnanolone
      and miglustat in a knock-out mouse model of NPC1 disease.
AB  - BACKGROUND: Niemann Pick disease type C1 is a neurodegenerative disease caused by
      mutations in the NPC1 gene, which result in accumulation of unesterified
      cholesterol and glycosphingolipids in the endosomal-lysosomal system as well as
      limiting membranes. We have previously shown the corneal involvement in NPC1
      pathology in form of intracellular inclusions in epithelial cells and
      keratocytes. The purpose of the present study was to clarify if these inclusions
      regress during combined substrate reduction- and by-product therapy (SRT and
      BPT). METHODOLOGY/PRINCIPAL FINDINGS: Starting at postnatal day 7 (P7) and
      thereafter, NPC1 knock-out mice (NPC1(-/-)) and wild type controls (NPC1(+/+))
      were injected with cyclodextrin/allopregnanolone weekly. Additionally, a daily
      miglustat injection started at P10 until P23. Starting at P23 the mice were fed
      powdered chow with daily addition of miglustat. The sham group was injected with
      0.9% NaCl at P7, thereafter daily starting at P10 until P23, and fed powdered
      chow starting at P23. For corneal examination, in vivo confocal laser-scanning
      microscopy (CLSM) was performed one day before experiment was terminated. Excised
      corneas were harvested for lipid analysis (HPLC/MS) and electron microscopy. In
      vivo CLSM demonstrated a regression of hyperreflective inclusions in all treated
      NPC1(-/-)mice. The findings varied between individual mice, demonstrating a
      regression, ranging from complete absence to pronounced depositions. The
      reflectivity of inclusions, however, was significantly lower when compared to
      untreated and sham-injected NPC1(-/-) mice. These confocal findings were
      confirmed by lipid analysis and electron microscopy. Another important CLSM
      finding revealed a distinct increase of mature dendritic cell number in corneas
      of all treated mice (NPC1(-/-) and NPC1(+/+)), including sham-treated ones.
      CONCLUSIONS/SIGNIFICANCE: The combined substrate reduction- and by-product
      therapy revealed beneficial effects on the cornea. In vivo CLSM is a non-invasive
      tool to monitor disease progression and treatment effects in NPC1 disorder.

PMID- 22163016
TI  - Type I IFN promotes IL-10 production from T cells to suppress Th17 cells and Th17
      associated autoimmune inflammation.
AB  - Whereas the immune system is essential for host defense against pathogen
      infection or endogenous danger signals, dysregulated innate and adaptive immune
      cells may facilitate harmful inflammatory or autoimmune responses. In the CNS,
      chronic inflammation plays an important role in the pathogenesis of
      neurodegenerative diseases such as multiple sclerosis (MS). Our previous study
      has demonstrated a critical role for the type I IFN induction and signaling
      pathways in constraining Th17-mediated experimental autoimmune encephalomyelitis
      (EAE), an animal model of human MS. However, it remains unknown if self-reactive
      Th17 cells can be reprogrammed to have less encephalitogenic activities or even
      have regulatory effects through modulation of innate pathways. In this study, we
      investigated the direct effects of type I IFN on Th17 cells. Our data show that
      IFNbeta treatment of T cells cultured under Th17 polarizing conditions resulted
      in reduced production of IL-17, but increased production of IL-10. We also found
      that IFNbeta induced IL-10 production by antigen specific T cells derived from
      immunized mice. Furthermore, IFNbeta treatment could suppress the
      encephalitogenic activity of myelin-specific T cells, and ameliorate clinical
      symptoms of EAE in an adoptive transfer model. Together, results from this study
      suggest that IFNbeta may induce antigen-specific T cells to produce IL-10, which
      in turn negatively regulate Th17-mediate inflammatory and autoimmune response.

PMID- 22163017
TI  - Funding source and research report quality in nutrition practice-related
      research.
AB  - BACKGROUND: The source of funding is one of many possible causes of bias in
      scientific research. One method of detecting potential for bias is to evaluate
      the quality of research reports. Research exploring the relationship between
      funding source and nutrition-related research report quality is limited and in
      other disciplines the findings are mixed. OBJECTIVE: The purpose of this study is
      to determine whether types of funding sources of nutrition research are
      associated with differences in research report quality. DESIGN: A retrospective
      study of research reporting quality, research design and funding source was
      conducted on 2539 peer reviewed research articles from the American Dietetic
      Association's Evidence Analysis Library(r) database. RESULTS: Quality rating
      frequency distributions indicate 43.3% of research reports were rated as
      positive, 50.1% neutral, and 6.6% as negative. Multinomial logistic regression
      results showed that while both funding source and type of research design are
      significant predictors of quality ratings (chi2 = 118.99, p<=0.001), the model's
      usefulness in predicting overall research report quality is little better than
      chance. Compared to research reports with government funding, those not
      acknowledging any funding sources, followed by studies with University/hospital
      funding were more likely to receive neutral vs positive quality ratings, OR =
      1.85, P <0.001 and OR = 1.54, P<0.001, respectively and those that did not report
      funding were more likely to receive negative quality ratings (OR = 4.97,
      P<0.001). After controlling for research design, industry funded research reports
      were no more likely to receive a neutral or negative quality rating than those
      funded by government sources. CONCLUSION: Research report quality cannot be
      accurately predicted from the funding source after controlling for research
      design. Continued vigilance to evaluate the quality of all research regardless of
      the funding source and to further understand other factors that affect quality
      ratings are warranted.

PMID- 22163018
TI  - DNA damage in plant herbarium tissue.
AB  - Dried plant herbarium specimens are potentially a valuable source of DNA. Efforts
      to obtain genetic information from this source are often hindered by an inability
      to obtain amplifiable DNA as herbarium DNA is typically highly degraded. DNA post
      mortem damage may not only reduce the number of amplifiable template molecules,
      but may also lead to the generation of erroneous sequence information. A
      qualitative and quantitative assessment of DNA post-mortem damage is essential to
      determine the accuracy of molecular data from herbarium specimens. In this study
      we present an assessment of DNA damage as miscoding lesions in herbarium
      specimens using 454-sequencing of amplicons derived from plastid, mitochondrial,
      and nuclear DNA. In addition, we assess DNA degradation as a result of strand
      breaks and other types of polymerase non-bypassable damage by quantitative real
      time PCR. Comparing four pairs of fresh and herbarium specimens of the same
      individuals we quantitatively assess post-mortem DNA damage, directly after
      specimen preparation, as well as after long-term herbarium storage. After
      specimen preparation we estimate the proportion of gene copy numbers of plastid,
      mitochondrial, and nuclear DNA to be 2.4-3.8% of fresh control DNA and 1.0-1.3%
      after long-term herbarium storage, indicating that nearly all DNA damage occurs
      on specimen preparation. In addition, there is no evidence of preferential
      degradation of organelle versus nuclear genomes. Increased levels of C->T/G->A
      transitions were observed in old herbarium plastid DNA, representing 21.8% of
      observed miscoding lesions. We interpret this type of post-mortem DNA damage
      derived modification to have arisen from the hydrolytic deamination of cytosine
      during long-term herbarium storage. Our results suggest that reliable sequence
      data can be obtained from herbarium specimens.

PMID- 22163019
TI  - IL-1alpha/IL-1R1 expression in chronic obstructive pulmonary disease and
      mechanistic relevance to smoke-induced neutrophilia in mice.
AB  - BACKGROUND: Cigarette smoking is the main risk factor for the development of
      chronic obstructive pulmonary disease (COPD), a major cause of morbidity and
      mortality worldwide. Despite this, the cellular and molecular mechanisms that
      contribute to COPD pathogenesis are still poorly understood. METHODOLOGY AND
      PRINCIPAL FINDINGS: The objective of this study was to assess IL-1 alpha and beta
      expression in COPD patients and to investigate their respective roles in
      perpetuating cigarette smoke-induced inflammation. Functional studies were
      pursued in smoke-exposed mice using gene-deficient animals, as well as blocking
      antibodies for IL-1alpha and beta. Here, we demonstrate an underappreciated role
      for IL-1alpha expression in COPD. While a strong correlation existed between IL
      1alpha and beta levels in patients during stable disease and periods of
      exacerbation, neutrophilic inflammation was shown to be IL-1alpha-dependent, and
      IL-1beta- and caspase-1-independent in a murine model of cigarette smoke
      exposure. As IL-1alpha was predominantly expressed by hematopoietic cells in COPD
      patients and in mice exposed to cigarette smoke, studies pursued in bone marrow
      chimeric mice demonstrated that the crosstalk between IL-1alpha+ hematopoietic
      cells and the IL-1R1+ epithelial cells regulates smoke-induced inflammation. IL
      1alpha/IL-1R1-dependent activation of the airway epithelium also led to
      exacerbated inflammatory responses in H1N1 influenza virus infected smoke-exposed
      mice, a previously reported model of COPD exacerbation. CONCLUSIONS AND
      SIGNIFICANCE: This study provides compelling evidence that IL-1alpha is central
      to the initiation of smoke-induced neutrophilic inflammation and suggests that IL
      1alpha/IL-1R1 targeted therapies may be relevant for limiting inflammation and
      exacerbations in COPD.

PMID- 22163020
TI  - Origin and properties of striatal local field potential responses to cortical
      stimulation: temporal regulation by fast inhibitory connections.
AB  - Evoked striatal field potentials are seldom used to study corticostriatal
      communication in vivo because little is known about their origin and
      significance. Here we show that striatal field responses evoked by stimulating
      the prelimbic cortex in mice are reduced by more than 90% after infusing the AMPA
      receptor antagonist CNQX close to the recording electrode. Moreover, the
      amplitude of local field responses and dPSPs recorded in striatal medium spiny
      neurons increase in parallel with increasing stimulating current intensity.
      Finally, the evoked striatal fields show several of the basic known properties of
      corticostriatal transmission, including paired pulse facilitation and
      topographical organization. As a case study, we characterized the effect of local
      GABA(A) receptor blockade on striatal field and multiunitary action potential
      responses to prelimbic cortex stimulation. Striatal activity was recorded through
      a 24 channel silicon probe at about 600 um from a microdialysis probe.
      Intrastriatal administration of the GABA(A) receptor antagonist bicuculline
      increased by 65+/-7% the duration of the evoked field responses. Moreover, the
      associated action potential responses were markedly enhanced during bicuculline
      infusion. Bicuculline enhancement took place at all the striatal sites that
      showed a response to cortical stimulation before drug infusion, but sites showing
      no field response before bicuculline remained unresponsive during GABA(A)
      receptor blockade. Thus, the data demonstrate that fast inhibitory connections
      exert a marked temporal regulation of input-output transformations within
      spatially delimited striatal networks responding to a cortical input. Overall, we
      propose that evoked striatal fields may be a useful tool to study corticostriatal
      synaptic connectivity in relation to behavior.

PMID- 22163021
TI  - Oseltamivir prescription and regulatory actions vis-a-vis abnormal behavior risk
      in Japan: drug utilization study using a nationwide pharmacy database.
AB  - BACKGROUND: In March 2007, a regulatory advisory was issued in Japan to restrict
      oseltamivir use in children aged 10-19 years because of safety concerns over
      abnormal behavior. The effectiveness and validity of regulatory risk minimization
      actions remain to be reviewed, despite their significant public health
      implications. To assess the impact of the regulatory actions on prescribing
      practices and safety reporting.  METHODOLOY/PRINICPAL FINDINGS: In this
      retrospective review of a nationwide pharmacy database, we analyzed 100,344
      dispensation records for oseltamivir and zanamivir for the period from November
      2006 to March 2009. The time trend in dispensations for these antiviral agents
      was presented before and after the regulatory actions, contrasted with intensity
      of media coverage and the numbers of spontaneous adverse reaction reports with
      regard to antivirals. The 2007 regulatory actions, together with its intense
      media coverage, reduced oseltamivir dispensation in targeted patients in fiscal
      year 2008 to 20.4% of that in fiscal year 2006, although influenza activities
      were comparable between these fiscal years. In contrast, zanamivir dispensation
      increased approximately nine-fold across all age groups. The number of abnormal
      behavior reports associated with oseltamivir in children aged 10-19 years
      decreased from fiscal year 2006 to 2008 (24 to 9 cases); this decline was offset
      by the increased number of reports of abnormal behavior in children under age 10
      (12 to 28 cases). The number of reports associated with zanamivir increased in
      proportion to increased dispensation of this drug (11 to 114 cases).
      CONCLUSIONS/SIGNIFICANCE: The 2007 actions effectively reduced oseltamivir
      prescriptions and the number of reports of abnormal behavior in the targeted
      group. The observed increase in abnormal behavior reports in oseltamivir patients
      under age 10 and in zanamivir patients suggests that these patient groups may
      also be at risk, calling into question the validity of the current discrimination
      by age and agent (Abstract translation is available in Japanese: Appendix S1).

PMID- 22163022
TI  - Identification of the midgut microbiota of An. stephensi and An. maculipennis for
      their application as a paratransgenic tool against malaria.
AB  - The midgut microbiota associated with Anopheles stephensi and Anopheles
      maculipennis (Diptera: Culicidae) was investigated for development of a
      paratransgenesis-based approach to control malaria transmission in Eastern
      Mediterranean Region (EMR). Here, we present the results of a polymerase chain
      reaction (PCR) and biochemical-based approaches to identify the female adult and
      larvae mosquitoe microbiota of these two major malaria vectors, originated from
      South Eastern and North of Iran. Plating the mosquito midgut contents from lab
      reared and field-collected Anopheles spp. was used for microbiota isolation. The
      gram-negative and gram-positive bacterial colonies were identified by Gram
      staining and specific mediums. Selected colonies were identified by differential
      biochemical tests and 16S rRNA gene sequence analysis. A number of 10 An.
      stephensi and 32 An. maculipennis adult mosquitoes and 15 An. stephensi and 7 An.
      maculipennis larvae were analyzed and 13 sequences of 16S rRNA gene bacterial
      species were retrieved, that were categorized in 3 classes and 8 families. The
      majority of the identified bacteria were belonged to the gamma-proteobacteria
      class, including Pseudomonas sp. and Aeromonas sp. and the others were some
      closely related to those found in other vector mosquitoes, including Pantoea,
      Acinetobacter, Brevundimonas, Bacillus, Sphingomonas, Lysinibacillus and
      Rahnella. The 16S rRNA sequences in the current study aligned with the reference
      strains available in GenBank were used for construction of the phylogenetic tree
      that revealed the relatedness among the bacteria identified. The presented data
      strongly encourage further investigations, to verify the potential role of the
      detected bacteria for the malaria control in Iran and neighboring countries.

PMID- 22163023
TI  - Selective coupling between theta phase and neocortical fast gamma oscillations
      during REM-sleep in mice.
AB  - BACKGROUND: The mammalian brain expresses a wide range of state-dependent network
      oscillations which vary in frequency and spatial extension. Such rhythms can
      entrain multiple neurons into coherent patterns of activity, consistent with a
      role in behaviour, cognition and memory formation. Recent evidence suggests that
      locally generated fast network oscillations can be systematically aligned to long
      range slow oscillations. It is likely that such cross-frequency coupling supports
      specific tasks including behavioural choice and working memory. PRINCIPAL
      FINDINGS: We analyzed temporal coupling between high-frequency oscillations and
      EEG theta activity (4-12 Hz) in recordings from mouse parietal neocortex. Theta
      was exclusively present during active wakefulness and REM-sleep. Fast
      oscillations occurred in two separate frequency bands: gamma (40-100 Hz) and fast
      gamma (120-160 Hz). Theta, gamma and fast gamma were more prominent during active
      wakefulness as compared to REM-sleep. Coupling between theta and the two types of
      fast oscillations, however, was more pronounced during REM-sleep. This state
      dependent cross-frequency coupling was particularly strong for theta-fast gamma
      interaction which increased 9-fold during REM as compared to active wakefulness.
      Theta-gamma coupling increased only by 1.5-fold. SIGNIFICANCE: State-dependent
      cross-frequency-coupling provides a new functional characteristic of REM-sleep
      and establishes a unique property of neocortical fast gamma oscillations.
      Interactions between defined patterns of slow and fast network oscillations may
      serve selective functions in sleep-dependent information processing.

PMID- 22163024
TI  - Molecular epidemiology of Campylobacter isolates from poultry production units in
      southern Ireland.
AB  - This study aimed to identify the sources and routes of transmission of
      Campylobacter in intensively reared poultry farms in the Republic of Ireland.
      Breeder flocks and their corresponding broilers housed in three growing
      facilities were screened for the presence of Campylobacter species from November
      2006 through September 2007. All breeder flocks tested positive for Campylobacter
      species (with C. jejuni and C. coli being identified). Similarly, all broiler
      flocks also tested positive for Campylobacter by the end of the rearing period.
      Faecal and environmental samples were analyzed at regular intervals throughout
      the rearing period of each broiler flock. Campylobacter was not detected in the
      disinfected house, or in one-day old broiler chicks. Campylobacter jejuni was
      isolated from environmental samples including air, water puddles, adjacent
      broiler flocks and soil. A representative subset of isolates from each farm was
      selected for further characterization using flaA-SVR sub-typing and multi-locus
      sequence typing (MLST) to determine if same-species isolates from different
      sources were indistinguishable or not. Results obtained suggest that no evidence
      of vertical transmission existed and that adequate cleaning/disinfection of
      broiler houses contributed to the prevention of carryover and cross
      contamination. Nonetheless, the environment appears to be a potential source of
      Campylobacter. The population structure of Campylobacter isolates from broiler
      farms in Southern Ireland was diverse and weakly clonal.

PMID- 22163025
TI  - How molecular competition influences fluxes in gene expression networks.
AB  - Often, in living cells different molecular species compete for binding to the
      same molecular target. Typical examples are the competition of genes for the
      transcription machinery or the competition of mRNAs for the translation
      machinery. Here we show that such systems have specific regulatory features and
      how they can be analysed. We derive a theory for molecular competition in
      parallel reaction networks. Analytical expressions for the response of network
      fluxes to changes in the total competitor and common target pools indicate the
      precise conditions for ultrasensitivity and intuitive rules for competitor
      strength. The calculations are based on measurable concentrations of the
      competitor-target complexes. We show that kinetic parameters, which are usually
      tedious to determine, are not required in the calculations. Given their
      simplicity, the obtained equations are easily applied to networks of any
      dimension. The new theory is illustrated for competing sigma factors in bacterial
      transcription and for a genome-wide network of yeast mRNAs competing for
      ribosomes. We conclude that molecular competition can drastically influence the
      network fluxes and lead to negative response coefficients and ultrasensitivity.
      Competitors that bind a large fraction of the target, like bacterial sigma(70),
      tend to influence competing pathways strongly. The less a competitor is saturated
      by the target, the more sensitive it is to changes in the concentration of the
      target, as well as to other competitors. As a consequence, most of the mRNAs in
      yeast turn out to respond ultrasensitively to changes in ribosome concentration.
      Finally, applying the theory to a genome-wide dataset we observe that high and
      low response mRNAs exhibit distinct Gene Ontology profiles.

PMID- 22163026
TI  - A high density consensus map of rye (Secale cereale L.) based on DArT markers.
AB  - BACKGROUND: Rye (Secale cereale L.) is an economically important crop, exhibiting
      unique features such as outstanding resistance to biotic and abiotic stresses and
      high nutrient use efficiency. This species presents a challenge to geneticists
      and breeders due to its large genome containing a high proportion of repetitive
      sequences, self incompatibility, severe inbreeding depression and tissue culture
      recalcitrance. The genomic resources currently available for rye are
      underdeveloped in comparison with other crops of similar economic importance. The
      aim of this study was to create a highly saturated, multilocus linkage map of rye
      via consensus mapping, based on Diversity Arrays Technology (DArT) markers.
      METHODOLOGY/PRINCIPAL FINDINGS: Recombinant inbred lines (RILs) from 5
      populations (564 in total) were genotyped using DArT markers and subjected to
      linkage analysis using Join Map 4.0 and Multipoint Consensus 2.2 software. A
      consensus map was constructed using a total of 9703 segregating markers. The
      average chromosome map length ranged from 199.9 cM (2R) to 251.4 cM (4R) and the
      average map density was 1.1 cM. The integrated map comprised 4048 loci with the
      number of markers per chromosome ranging from 454 for 7R to 805 for 4R. In
      comparison with previously published studies on rye, this represents an eight
      fold increase in the number of loci placed on a consensus map and a more than two
      fold increase in the number of genetically mapped DArT markers.
      CONCLUSIONS/SIGNIFICANCE: Through the careful choice of marker type, mapping
      populations and the use of software packages implementing powerful algorithms for
      map order optimization, we produced a valuable resource for rye and triticale
      genomics and breeding, which provides an excellent starting point for more in
      depth studies on rye genome organization.

PMID- 22163027
TI  - Dietary essential amino acids affect the reproduction of the keystone herbivore
      Daphnia pulex.
AB  - Recent studies have indicated that nitrogen availability can be an important
      determinant of primary production in freshwater lakes and that herbivore growth
      can be limited by low dietary nitrogen availability. Furthermore, a lack of
      specific essential nitrogenous biochemicals (such as essential amino acids) might
      be another important constraint on the fitness of consumers. This might be of
      particular importance for cladoceran zooplankton, which can switch between two
      alternative reproductive strategies--the production of subitaneously developing
      and resting eggs. Here, we hypothesize that both the somatic growth and the type
      of reproduction of the aquatic keystone herbivore Daphnia is limited by the
      availability of specific essential amino acids in the diet. In laboratory
      experiments, we investigated this hypothesis by feeding a high quality
      phytoplankton organism (Cryptomonas) and a green alga of moderate nutritional
      quality (Chlamydomonas) to a clone of Daphnia pulex with and without the addition
      of essential amino acids. The somatic growth of D. pulex differed between the
      algae of different nutritional quality, but not dependent on the addition of
      dissolved amino acids. However, in reproduction experiments, where moderate
      crowding conditions at saturating food quantities were applied, addition of the
      essential amino acids arginine and histidine (but not lysine and threonine)
      increased the total number and the developmental stage of subitaneous eggs. While
      D. pulex did not produce resting eggs on Cryptomonas, relatively high numbers of
      resting eggs were released on Chlamydomonas. When arginine and histidine were
      added to the green algal diet, the production of resting eggs was effectively
      suppressed. This demonstrates the high, but previously overlooked importance of
      single essential amino acids for the reproductive strategy of the aquatic
      keystone herbivore Daphnia.

PMID- 22163029
TI  - Fast detection of unexpected sound intensity decrements as revealed by human
      evoked potentials.
AB  - The detection of deviant sounds is a crucial function of the auditory system and
      is reflected by the automatically elicited mismatch negativity (MMN), an auditory
      evoked potential at 100 to 250 ms from stimulus onset. It has recently been shown
      that rarely occurring frequency and location deviants in an oddball paradigm
      trigger a more negative response than standard sounds at very early latencies in
      the middle latency response of the human auditory evoked potential. This fast and
      early ability of the auditory system is corroborated by the finding of neurons in
      the animal auditory cortex and subcortical structures, which restore their
      adapted responsiveness to standard sounds, when a rare change in a sound feature
      occurs. In this study, we investigated whether the detection of intensity
      deviants is also reflected at shorter latencies than those of the MMN. Auditory
      evoked potentials in response to click sounds were analyzed regarding the
      auditory brain stem response, the middle latency response (MLR) and the MMN. Rare
      stimuli with a lower intensity level than standard stimuli elicited (in addition
      to an MMN) a more negative potential in the MLR at the transition from the Na to
      the Pa component at circa 24 ms from stimulus onset. This finding, together with
      the studies about frequency and location changes, suggests that the early
      automatic detection of deviant sounds in an oddball paradigm is a general
      property of the auditory system.

PMID- 22163028
TI  - Differential roles of HOW in male and female Drosophila germline differentiation.
AB  - The adult gonads in both male and female Drosophila melanogaster produce gametes
      that originate from a regenerative pool of germline stem cells (GSCs). The
      differentiation programme that produces gametes must be co-ordinated with GSC
      maintenance and proliferation in order to regulate tissue regeneration. The HOW
      RNA-binding protein has been shown to maintain mitotic progression of male GSCs
      and their daughters by maintenance of Cyclin B expression as well as suppressing
      accumulation of the differentiation factor Bam. Loss of HOW function in the male
      germline results in loss of GSCs due to a delay in G2 and subsequent apoptosis.
      Here we show that female how mutant GSCs do not have any cell cycle defects
      although HOW continues to bind bam mRNA and suppress Bam expression. The role of
      HOW in suppressing germ cell Bam expression appears to be conserved between
      sexes, leading to different cellular outcomes in how mutants due to the different
      functions of Bam. In addition the role in maintaining Cyclin B expression has not
      been conserved so female how GSCs differentiate rather than arrest.

PMID- 22163030
TI  - Statins promote the regression of atherosclerosis via activation of the CCR7
      dependent emigration pathway in macrophages.
AB  - HMG-CoA reductase inhibitors (statins) decrease atherosclerosis by lowering low
      density-lipoprotein cholesterol. Statins are also thought to have additional anti
      atherogenic properties, yet defining these non-conventional modes of statin
      action remains incomplete. We have previously developed a novel mouse transplant
      model of atherosclerosis regression in which aortic segments from diseased donors
      are placed into normolipidemic recipients. With this model, we demonstrated the
      rapid loss of CD68+ cells (mainly macrophages) in plaques through the induction
      of a chemokine receptor CCR7-dependent emigration process. Because the human and
      mouse CCR7 promoter contain Sterol Response Elements (SREs), we hypothesized that
      Sterol Regulatory Element Binding Proteins (SREBPs) are involved in increasing
      CCR7 expression and through this mechanism, statins would promote CD68+ cell
      emigration from plaques. We examined whether statin activation of the SREBP
      pathway in vivo would induce CCR7 expression and promote macrophage emigration
      from plaques. We found that western diet-fed apoE(-/-) mice treated with either
      atorvastatin or rosuvastatin led to a substantial reduction in the CD68+ cell
      content in the plaques despite continued hyperlipidemia. We also observed a
      significant increase in CCR7 mRNA in CD68+ cells from both the atorvastatin and
      rosuvastatin treated mice associated with emigration of CD68+ cells from plaques.
      Importantly, CCR7(-/-)/apoE(-/-) double knockout mice failed to display a
      reduction in CD68+ cell content upon statin treatment. Statins also affected the
      recruitment of transcriptional regulatory proteins and the organization of the
      chromatin at the CCR7 promoter to increase the transcriptional activity. Statins
      promote the beneficial remodeling of plaques in diseased mouse arteries through
      the stimulation of the CCR7 emigration pathway in macrophages. Therefore, statins
      may exhibit some of their clinical benefits by not only retarding the progression
      of atherosclerosis, but also accelerating its regression.

PMID- 22163031
TI  - Alkyl-glycerol rescues plasmalogen levels and pathology of ether-phospholipid
      deficient mice.
AB  - A deficiency of plasmalogens, caused by impaired peroxisomal metabolism affects
      normal development and multiple organs in adulthood. Treatment options aimed at
      restoring plasmalogen levels may be relevant for the therapy of peroxisomal and
      non-peroxisomal disorders. In this study we determined the in vivo efficacy of an
      alkyl glycerol (AG), namely, 1-O-octadecyl-rac-glycerol, as a therapeutic agent
      for defects in plasmalogen synthesis. To achieve this, Pex7 knockout mice, a
      mouse model for Rhizomelic Chondrodysplasia Punctata type 1 characterized by the
      absence of plasmalogens, and WT mice were fed a control diet or a diet containing
      2% alkyl-glycerol. Plasmalogen levels were measured in target organs and the
      biochemical data were correlated with the histological analysis of affected
      organs. Plasmalogen levels in all peripheral tissues of Pex7 KO mice fed the AG
      diet for 2 months normalized to the levels of AG fed WT mice. In nervous tissues
      of Pex7 KO mice fed the AG-diet, plasmalogen levels were significantly increased
      compared to control fed KO mice. Histological analysis of target organs revealed
      that the AG-diet was able to stop the progression of the pathology in testis,
      adipose tissue and the Harderian gland. Interestingly, the latter tissues are
      characterized by the presence of lipid droplets which were absent or reduced in
      size and number when ether-phospholipids are lacking, but which can be restored
      with the AAG treatment. Furthermore, nerve conduction in peripheral nerves was
      improved. When given prior to the occurrence of major pathological changes, the
      AG-diet prevented or ameliorated the pathology observed in Pex7 KO mice depending
      on the degree of plasmalogen restoration. This study provides evidence of the
      beneficial effects of treating a plasmalogen deficiency with alkyl-glycerol.

PMID- 22163032
TI  - Corneal epithelium expresses a variant of P2X(7) receptor in health and disease.
AB  - Improper wound repair of the corneal epithelium can alter refraction of light
      resulting in impaired vision. We have shown that ATP is released after injury,
      activates purinergic receptor signaling pathways and plays a major role in wound
      closure. In many cells or tissues, ATP activates P2X(7) receptors leading to
      cation fluxes and cytotoxicity. The corneal epithelium is an excellent model to
      study the expression of both the full-length P2X(7) form (defined as the
      canonical receptor) and its truncated forms. When Ca(2+) mobilization is induced
      by BzATP, a P2X(7) agonist, it is attenuated in the presence of extracellular
      Mg(2+) or Zn(2+), negligible in the absence of extracellular Ca(2+), and
      inhibited by the competitive P2X7 receptor inhibitor, A438079. BzATP enhanced
      phosphorylation of ERK. Together these responses indicate the presence of a
      canonical or full-length P2X(7) receptor. In addition BzATP enhanced epithelial
      cell migration, and transfection with siRNA to the P2X(7) receptor reduced cell
      migration. Furthermore, sustained activation did not induce dye uptake indicating
      the presence of truncated or variant forms that lack the ability to form large
      pores. Reverse transcription-polymerase chain reaction and Northern blot analysis
      revealed a P2X(7) splice variant. Western blots identified a full-length and
      truncated form, and the expression pattern changed as cultures progressed from
      monolayer to stratified. Cross-linking gels demonstrated the presence of homo-
      and heterotrimers. We examined epithelium from age matched diabetic and non
      diabetic corneas patients and detected a 4-fold increase in P2X(7) mRNA from
      diabetic corneal epithelium compared to non-diabetic controls and an increased
      trend in expression of P2X(7)variant mRNA. Taken together, these data indicate
      that corneal epithelial cells express full-length and truncated forms of P2X(7),
      which ultimately allows P2X(7) to function as a multifaceted receptor that can
      mediate cell proliferation and migration or cell death.

PMID- 22163033
TI  - Characterization of a new mouse model for peripheral T cell lymphoma in humans.
AB  - Peripheral T cell lymphomas (PTCLs) are associated with a poor prognosis due to
      often advanced disease at the time of diagnosis and due to a lack of efficient
      therapeutic options. Therefore, appropriate animal models of PTCL are vital to
      improve clinical management of this disease. Here, we describe a monoclonal
      CD8(+) CD4(-) alphabeta T cell receptor Vbeta2(+) CD28(+) T cell lymphoma line,
      termed T8-28. T8-28 cells were isolated from an un-manipulated adult BALB/c mouse
      housed under standard pathogen-free conditions. T8-28 cells induced terminal
      malignancy upon adoptive transfer into syngeneic BALB/c mice. Despite
      intracellular expression of the cytotoxic T cell differentiation marker granzyme
      B, T8-28 cells appeared to be defective with respect to cytotoxic activity as
      read-out in vitro. Among the protocols tested, only addition of interleukin 2 in
      vitro could partially compensate for the in vivo micro-milieu in promoting growth
      of the T8-28 lymphoma cells.

PMID- 22163034
TI  - The role of Dicer protein partners in the processing of microRNA precursors.
AB  - One of the cellular functions of the ribonuclease Dicer is to process microRNA
      precursors (pre-miRNAs) into mature microRNAs (miRNAs). Human Dicer performs this
      function in cooperation with its protein partners, AGO2, PACT and TRBP. The exact
      role of these accessory proteins in Dicer activity is still poorly understood. In
      this study, we used the northern blotting technique to investigate pre-miRNA
      cleavage efficiency and specificity after depletion of AGO2, PACT and TRBP by
      RNAi. The results showed that the inhibition of either Dicer protein partner
      substantially affected not only miRNA levels but also pre-miRNA levels, and it
      had a rather minor effect on the specificity of Dicer cleavage. The analysis of
      the Dicer cleavage products generated in vitro revealed the presence of a
      cleavage intermediate when pre-miRNA was processed by recombinant Dicer alone.
      This intermediate was not observed during pre-miRNA cleavage by endogenous Dicer.
      We demonstrate that AGO2, PACT and TRBP were required for the efficient
      functioning of Dicer in cells, and we suggest that one of the roles of these
      proteins is to assure better synchronization of cleavages triggered by two RNase
      III domains of Dicer.

PMID- 22163035
TI  - SUMO-SIM interactions regulate the activity of RGSZ2 proteins.
AB  - The RGSZ2 gene, a regulator of G protein signaling, has been implicated in
      cognition, Alzheimer's disease, panic disorder, schizophrenia and several human
      cancers. This 210 amino acid protein is a GTPase accelerating protein (GAP) on
      Galphai/o/z subunits, binds to the N terminal of neural nitric oxide synthase
      (nNOS) negatively regulating the production of nitric oxide, and binds to the
      histidine triad nucleotide-binding protein 1 at the C terminus of different G
      protein-coupled receptors (GPCRs). We now describe a novel regulatory mechanism
      of RGS GAP function through the covalent incorporation of Small Ubiquitin-like
      MOdifiers (SUMO) into RGSZ2 RGS box (RH) and the SUMO non covalent binding with
      SUMO-interacting motifs (SIM): one upstream of the RH and a second within this
      region. The covalent attachment of SUMO does not affect RGSZ2 binding to GPCR
      activated GalphaGTP subunits but abolishes its GAP activity. By contrast, non
      covalent binding of SUMO with RH SIM impedes RGSZ2 from interacting with
      GalphaGTP subunits. Binding of SUMO to the RGSZ2 SIM that lies outside the RH
      does not affect GalphaGTP binding or GAP activity, but it could lead to
      regulatory interactions with sumoylated proteins. Thus, sumoylation and SUMO-SIM
      interactions constitute a new regulatory mechanism of RGS GAP function and
      therefore of GPCR cell signaling as well.

PMID- 22163036
TI  - Disabled-1 alternative splicing in human fetal retina and neural tumors.
AB  - BACKGROUND: The Reelin-Dab1 signaling pathway plays a critical role in the
      positioning of migrating neurons, dendrite formation and lamination in the
      developing central nervous system. We have previously identified two
      alternatively spliced forms of Dab1 in the developing chick retina: an early
      form, Dab1-E, expressed in retinal progenitor cells, and a late form, Dab1 or
      Dab1-L, expressed in amacrine and ganglion cells. Compared to Dab1-L, Dab1-E
      lacks two exons that encode two Src family kinase (SFK) phosphorylation sites.
      PRINCIPAL FINDINGS: Both Dab1-L and Dab1-E-like transcripts were identified in
      human fetal retina. Expression of human Dab1-L in primary chick retinal cultures
      resulted in Reelin-mediated induction of SFK phosphorylation and formation of
      neurite-like processes. In contrast, human Dab1-E-expressing cells retained an
      undifferentiated morphology. The human Dab1 gene is located within a common
      fragile site, and it has been postulated that it may function as a tumor
      suppressor. Analysis of Dab1 splice forms in retinoblastoma and neuroblastoma
      tumor cells revealed relative enrichment of Dab1-L-like (includes exons 7 and 8)
      and Dab1-E-like (excludes exons 7 and 8) transcripts in retinoblastoma and
      neuroblastoma, respectively. Treatment of retinoblastoma cell line RB522A with
      Reelin resulted in increased tyrosine phosphorylation of Dab1. As Nova2 has
      previously been implicated in the exclusion of exons 9B and 9C in Dab1, we
      examined the expression of this splicing factor in neuroblastoma and
      retinoblastoma cell lines. Nova2 was only detected in neuroblastoma cells,
      suggesting a correlation between Nova2 expression and increased levels of Dab1-E
      like splice forms in neuroblastoma. CONCLUSIONS: These results indicate that
      alternative splicing of Dab1 is conserved in avian and mammalian species, with
      Dab1-L driving SFK phosphorylation in both species. Dab1-E- and Dab-L-like
      isoforms are also expressed in childhood neural tumors, with preferential
      enrichment of Dab1-L-like and Dab1-E-like isoforms in retinoblastoma and
      neuroblastoma, respectively.

PMID- 22163037
TI  - Tyrosine phosphorylation of Rac1: a role in regulation of cell spreading.
AB  - Rac1 influences a multiplicity of vital cellular- and tissue-level control
      functions, making it an important candidate for targeted therapeutics. The
      activity of the Rho family member Cdc42 has been shown to be modulated by
      tyrosine phosphorylation at position 64. We therefore investigated consequences
      of the point mutations Y64F and Y64D in Rac1. Both mutations altered cell
      spreading from baseline in the settings of wild type, constitutively active, or
      dominant negative Rac1 expression, and were accompanied by differences in Rac1
      targeting to focal adhesions. Rac1-Y64F displayed increased GTP-binding,
      increased association with betaPIX, and reduced binding with RhoGDI as compared
      with wild type Rac1. Rac1-Y64D had less binding to PAK than Rac1-WT or Rac1-64F.
      In vitro assays demonstrated that Y64 in Rac1 is a target for FAK and Src. Taken
      together, these data suggest a mechanism for the regulation of Rac1 activity by
      non-receptor tyrosine kinases, with consequences for membrane extension.

PMID- 22163038
TI  - Prevalence and risk factors for vitamin C deficiency in north and south India: a
      two centre population based study in people aged 60 years and over.
AB  - BACKGROUND: Studies from the UK and North America have reported vitamin C
      deficiency in around 1 in 5 men and 1 in 9 women in low income groups. There are
      few data on vitamin C deficiency in resource poor countries. OBJECTIVES: To
      investigate the prevalence of vitamin C deficiency in India. DESIGN: We carried
      out a population-based cross-sectional survey in two areas of north and south
      India. Randomly sampled clusters were enumerated to identify people aged 60 and
      over. Participants (75% response rate) were interviewed for tobacco, alcohol,
      cooking fuel use, 24 hour diet recall and underwent anthropometry and blood
      collection. Vitamin C was measured using an enzyme-based assay in plasma
      stabilized with metaphosphoric acid. We categorised vitamin C status as deficient
      (<11 umol/L), sub-optimal (11-28 umol/L) and adequate (>28 umol/L). We
      investigated factors associated with vitamin C deficiency using multivariable
      Poisson regression. RESULTS: The age, sex and season standardized prevalence of
      vitamin C deficiency was 73.9% (95% confidence Interval, CI 70.4,77.5) in 2668
      people in north India and 45.7% (95% CI 42.5,48.9) in 2970 from south India. Only
      10.8% in the north and 25.9% in the south met the criteria for adequate levels.
      Vitamin C deficiency varied by season, and was more prevalent in men, with
      increasing age, users of tobacco and biomass fuels, in those with anthropometric
      indicators of poor nutrition and with lower intakes of dietary vitamin C.
      CONCLUSIONS: In poor communities, such as in our study, consideration needs to be
      given to measures to improve the consumption of vitamin C rich foods and to
      discourage the use of tobacco.

PMID- 22163039
TI  - Generation of variants in Listeria monocytogenes continuous-flow biofilms is
      dependent on radical-induced DNA damage and RecA-mediated repair.
AB  - The food-borne pathogen Listeria monocytogenes is a gram-positive microaerophilic
      facultative anaerobic rod and the causative agent of the devastating disease
      listeriosis. L. monocytogenes is able to form biofilms in the food processing
      environment. Since biofilms are generally hard to eradicate, they can function as
      a source for food contamination. In several occasions biofilms have been
      identified as a source for genetic variability, which potentially can result in
      adaptation of strains to food processing or clinical conditions. However, nothing
      is known about mutagenesis in L. monocytogenes biofilms and the possible
      mechanisms involved. In this study, we showed that the generation of genetic
      variants was specifically induced in continuous-flow biofilms of L.
      monocytogenes, but not in static biofilms. Using specific dyes and radical
      inhibitors, we showed that the formation of superoxide and hydroxyl radicals was
      induced in continuous-flow biofilms, which was accompanied with in an increase in
      DNA damage. Promoter reporter studies showed that recA, which is an important
      component in DNA repair and the activator of the SOS response, is activated in
      continuous-flow biofilms and that activation was dependent on radical-induced DNA
      damage. Furthermore, continuous-flow biofilm experiments using an in-frame recA
      deletion mutant verified that RecA is required for induced generation of genetic
      variants. Therefore, we can conclude that generation of genetic variants in L.
      monocytogenes continuous-flow biofilms results from radical-induced DNA damage
      and RecA-mediated mutagenic repair of the damaged DNA.

PMID- 22163040
TI  - High ACSL5 transcript levels associate with systemic lupus erythematosus and
      apoptosis in Jurkat T lymphocytes and peripheral blood cells.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a prototypical autoimmune
      disease in which increased apoptosis and decreased apoptotic cells removal has
      been described as most relevant in the pathogenesis. Long-chain acyl-coenzyme A
      synthetases (ACSLs) have been involved in the immunological dysfunction of mouse
      models of lupus-like autoimmunity and apoptosis in different in vitro cell
      systems. The aim of this work was to assess among the ACSL isoforms the
      involvement of ACSL2, ACSL4 and ACSL5 in SLE pathogenesis. FINDINGS: With this
      end, we determined the ACSL2, ACSL4 and ACSL5 transcript levels in peripheral
      blood mononuclear cells (PBMCs) of 45 SLE patients and 49 healthy controls by
      quantitative real time-PCR (q-PCR). We found that patients with SLE had higher
      ACSL5 transcript levels than healthy controls [median (range), healthy controls =
      16.5 (12.3-18.0) vs. SLE = 26.5 (17.8-41.7), P = 3.9*10 E-5] but no differences
      were found for ACSL2 and ACSL4. In in vitro experiments, ACSL5 mRNA expression
      was greatly increased when inducing apoptosis in Jurkat T cells and PBMCs by
      Phorbol-Myristate-Acetate plus Ionomycin (PMA+Io). On the other hand, short
      interference RNA (siRNA)-mediated silencing of ACSL5 decreased induced apoptosis
      in Jurkat T cells up to the control levels as well as decreased mRNA expression
      of FAS, FASLG and TNF. CONCLUSIONS: These findings indicate that ACSL5 may play a
      role in the apoptosis that takes place in SLE. Our results point to ACSL5 as a
      potential novel functional marker of pathogenesis and a possible therapeutic
      target in SLE.

PMID- 22163041
TI  - Solutions to the cocktail party problem in insects: selective filters, spatial
      release from masking and gain control in tropical crickets.
AB  - BACKGROUND: Insects often communicate by sound in mixed species choruses; like
      humans and many vertebrates in crowded social environments they thus have to
      solve cocktail-party-like problems in order to ensure successful communication
      with conspecifics. This is even more a problem in species-rich environments like
      tropical rainforests, where background noise levels of up to 60 dB SPL have been
      measured. PRINCIPAL FINDINGS: Using neurophysiological methods we investigated
      the effect of natural background noise (masker) on signal detection thresholds in
      two tropical cricket species Paroecanthus podagrosus and Diatrypa sp., both in
      the laboratory and outdoors. We identified three 'bottom-up' mechanisms which
      contribute to an excellent neuronal representation of conspecific signals despite
      the masking background. First, the sharply tuned frequency selectivity of the
      receiver reduces the amount of masking energy around the species-specific calling
      song frequency. Laboratory experiments yielded an average signal-to-noise ratio
      (SNR) of -8 dB, when masker and signal were broadcast from the same side.
      Secondly, displacing the masker by 180 degrees  from the signal improved SNRs by
      further 6 to 9 dB, a phenomenon known as spatial release from masking.
      Surprisingly, experiments carried out directly in the nocturnal rainforest
      yielded SNRs of about -23 dB compared with those in the laboratory with the same
      masker, where SNRs reached only -14.5 and -16 dB in both species. Finally, a
      neuronal gain control mechanism enhances the contrast between the responses to
      signals and the masker, by inhibition of neuronal activity in interstimulus
      intervals. CONCLUSIONS: Thus, conventional speaker playbacks in the lab
      apparently do not properly reconstruct the masking noise situation in a spatially
      realistic manner, since under real world conditions multiple sound sources are
      spatially distributed in space. Our results also indicate that without knowledge
      of the receiver properties and the spatial release mechanisms the detrimental
      effect of noise may be strongly overestimated.

PMID- 22163042
TI  - Inhibition of interferon induction and action by the nairovirus Nairobi sheep
      disease virus/Ganjam virus.
AB  - The Nairoviruses are an important group of tick-borne viruses that includes
      pathogens of man (Crimean Congo hemorrhagic fever virus) and livestock animals
      (Dugbe virus, Nairobi sheep disease virus (NSDV)). NSDV is found in large parts
      of East Africa and the Indian subcontinent (where it is known as Ganjam virus).
      We have investigated the ability of NSDV to antagonise the induction and actions
      of interferon. Both pathogenic and apathogenic isolates could actively inhibit
      the induction of type 1 interferon, and also blocked the signalling pathways of
      both type 1 and type 2 interferons. Using transient expression of viral proteins
      or sections of viral proteins, these activities all mapped to the ovarian tumour
      like protease domain (OTU) found in the viral RNA polymerase. Virus infection, or
      expression of this OTU domain in transfected cells, led to a great reduction in
      the incorporation of ubiquitin or ISG15 protein into host cell proteins. Point
      mutations in the OTU that inhibited the protease activity also prevented it from
      antagonising interferon induction and action. Interestingly, a mutation at a
      peripheral site, which had little apparent effect on the ability of the OTU to
      inhibit ubiquitination and ISG15ylation, removed the ability of the OTU to block
      the induction of type 1 and the action of type 2 interferons, but had a lesser
      effect on the ability to block type 1 interferon action, suggesting that targets
      other than ubiquitin and ISG15 may be involved in the actions of the viral OTU.

PMID- 22163043
TI  - The KCNJ11 E23K polymorphism and progression of glycaemia in Southern Chinese: a
      long-term prospective study.
AB  - CONTEXT: The KCNJ11 E23K variant is associated with type 2 diabetes mellitus
      (T2DM) in cross-sectional studies, but conflicting findings have been reported
      from prospective studies. OBJECTIVE: This study aimed to evaluate whether the
      E23K variant could predict glycaemic progression in a Southern Chinese
      population. METHODS/PRINCIPAL FINDINGS: We performed a long-term prospective
      study on 1912 subjects from the Hong Kong Cardiovascular Risk Factors Prevalence
      Study (CRISPS). The KCNJ11 E23K variant was associated with the progression to
      prediabetes after a median interval of 12 years on multinomial logistic
      regression analysis, even after adjustment for traditional risk factors (OR 1.29,
      P(age, sex, BMI and fasting plasma glucose [FPG] adjusted) = 0.02). Based on Cox
      proportional hazard regression analysis, the E23K variant also predicted incident
      prediabetes (HR 1.18, P(age, sex, BMI and FPG adjusted)= 0.021). However, E23K
      was not associated with the progression to T2DM in either multinomial or Cox
      regression analysis, and the association of E23K with glycaemic progression to
      either prediabetes or T2DM was significant only in unadjusted Cox regression
      analysis (P = 0.039). In a meta-analysis of eight prospective studies including
      our own, involving 15680 subjects, the E23K variant was associated with incident
      T2DM (fixed effect: OR 1.10, P = 4*10(-3); random effect: OR 1.11, P = 0.035).
      CONCLUSIONS: Our study has provided supporting evidence for the role of the E23K
      variant in glycaemic progression in Chinese, with its effect being more evident
      in the early stage of T2DM, as the subjects progressed from normal glucose
      tolerance to prediabetes.

PMID- 22163045
TI  - Do singing rock hyraxes exploit conspecific calls to gain attention?
AB  - Signal detection theory predicts that signals directed at distant or busy
      receivers in noisy backgrounds will begin with an alert component, in order to
      draw attention. Instead of an alert component, however, animals could get the
      same effect by using an external stimulus. Here we combined observations of free
      living rock hyraxes (Procavia capensis) with playback experiments to elucidate
      the circumstances under which males begin singing. We show that males sing
      following hyrax pup screams, which elicit a strong response from hyraxes within
      hearing distance, which are potential receivers. We hypothesize that singers
      enhance their singing display by exploiting the rarely emitted pup screams. To
      our knowledge, our findings are the first indication that animals may enhance
      signal reception by exploiting conspecifics' signals and the differential
      attention to these signals. We suggest that the utilization of external stimuli
      by signalers may be widespread, as an adaptive strategy for communication in
      complex environments.

PMID- 22163044
TI  - Biochemical and molecular mechanisms of folate transport in rat pancreas;
      interference with ethanol ingestion.
AB  - Folic acid is an essential nutrient that is required for one-carbon biosynthetic
      processes and for methylation of biomolecules. Deficiency of this micronutrient
      leads to disturbances in normal physiology of cell. Chronic alcoholism is well
      known to be associated with folate deficiency which is due, in part to folate
      malabsorption. The present study deals with the mechanistic insights of reduced
      folate absorption in pancreas during chronic alcoholism. Male Wistar rats were
      fed 1 g/kg body weight/day ethanol (20% solution) orally for 3 months and the
      mechanisms of alcohol associated reduced folate uptake was studied in pancreas.
      The folate transport system in the pancreatic plasma membrane (PPM) was found to
      be acidic pH dependent one. The transporters proton coupled folate transporter
      (PCFT) and reduced folate carrier (RFC) are involved in folate uptake across PPM.
      The folate transporters were found to be associated with lipid raft microdomain
      of the PPM. Ethanol ingestion decreased the folate transport by reducing the
      levels of folate transporter molecules in lipid rafts at the PPM. The decreased
      transport efficiency of the PPM was reflected as reduced folate levels in
      pancreas. The chronic ethanol ingestion led to decreased pancreatic folate
      uptake. The decreased levels of PCFT and RFC expression in rat PPM were due to
      decreased association of these proteins with lipid rafts (LR) at the PPM.

PMID- 22163046
TI  - Role of Toll-like receptor (TLR) 2 in experimental Bacillus cereus
      endophthalmitis.
AB  - Bacillus cereus causes a uniquely rapid and blinding intraocular infection,
      endophthalmitis. B. cereus replicates in the eye, synthesizes numerous toxins,
      and incites explosive intraocular inflammation. The mechanisms involved in the
      rapid and explosive intraocular immune response have not been addressed. Because
      Toll-like receptors (TLRs) are integral to the initial recognition of organisms
      during infection, we hypothesized that the uniquely explosive immune response
      observed during B. cereus endophthalmitis is directly influenced by the presence
      of TLR2, a known gram-positive pathogen recognition receptor. To address this
      hypothesis, we compared the courses of experimental B. cereus endophthalmitis in
      wild type C57BL/6J mice to that of age-matched homozygous TLR2(-/-) mice. Output
      parameters included analysis of bacterial growth, inflammatory cell (PMN)
      infiltration, cytokine/chemokine kinetics, retinal function testing, and
      histology, with N>=4 eyes/assay/time point/mouse strain. B. cereus grew at
      similar rates to10(8) CFU/eye by 12 h, regardless of the mouse strain. Retinal
      function was preserved to a greater degree in infected TLR2(-/-) eyes compared to
      that of infected wild type eyes, but infected eyes of both mouse strains lost
      significant function. Retinal architecture was preserved in infected TLR2(-/-)
      eyes, with limited retinal and vitreal cellular infiltration compared to that of
      infected wild type eyes. Ocular myeloperoxidase activities corroborated these
      results. In general, TNFalpha, IFNgamma, IL6, and KC were detected in greater
      concentrations in infected wild type eyes than in infected TLR2(-/-) eyes. The
      absence of TLR2 resulted in decreased intraocular proinflammatory
      cytokine/chemokine levels and altered recruitment of inflammatory cells into the
      eye, resulting in less intraocular inflammation and preservation of retinal
      architecture, and a slightly greater degree of retinal function. These results
      demonstrate TLR2 is an important component of the initial ocular response to B.
      cereus endophthalmitis.

PMID- 22163047
TI  - Estimating temporal trend in the presence of spatial complexity: a Bayesian
      hierarchical model for a wetland plant population undergoing restoration.
AB  - Monitoring programs that evaluate restoration and inform adaptive management are
      important for addressing environmental degradation. These efforts may be well
      served by spatially explicit hierarchical approaches to modeling because of
      unavoidable spatial structure inherited from past land use patterns and other
      factors. We developed bayesian hierarchical models to estimate trends from annual
      density counts observed in a spatially structured wetland forb (Camassia quamash
      [camas]) population following the cessation of grazing and mowing on the study
      area, and in a separate reference population of camas. The restoration site was
      bisected by roads and drainage ditches, resulting in distinct subpopulations
      ("zones") with different land use histories. We modeled this spatial structure by
      fitting zone-specific intercepts and slopes. We allowed spatial covariance
      parameters in the model to vary by zone, as in stratified kriging, accommodating
      anisotropy and improving computation and biological interpretation. Trend
      estimates provided evidence of a positive effect of passive restoration, and the
      strength of evidence was influenced by the amount of spatial structure in the
      model. Allowing trends to vary among zones and accounting for topographic
      heterogeneity increased precision of trend estimates. Accounting for spatial
      autocorrelation shifted parameter coefficients in ways that varied among zones
      depending on strength of statistical shrinkage, autocorrelation and topographic
      heterogeneity--a phenomenon not widely described. Spatially explicit estimates of
      trend from hierarchical models will generally be more useful to land managers
      than pooled regional estimates and provide more realistic assessments of
      uncertainty. The ability to grapple with historical contingency is an appealing
      benefit of this approach.

PMID- 22163048
TI  - Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus
      immortalized cells.
AB  - Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human
      tumours of lymphoid and epithelial origin. The virus infects and immortalizes B
      cells establishing a persistent latent infection characterized by varying
      patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1
      activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in
      colon, breast and ovarian cancer tissues and we have detected selective high
      level RGC-32 protein expression in EBV-immortalized latency III cells.
      Significantly, we show that overexpression of RGC-32 in B cells is sufficient to
      disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC
      32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at
      high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative
      BL cell-lines, although RGC-32 protein expression is not detectable. We show that
      RGC-32 mRNA expression is elevated in latency I cells due to transcriptional
      activation by high levels of the differentially expressed RUNX1c transcription
      factor. We found that proteosomal degradation or blocked cytoplasmic export of
      the RGC-32 message were not responsible for the lack of RGC-32 protein expression
      in latency I cells. Significantly, analysis of the ribosomal association of the
      RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts
      were associated with multiple ribosomes in both cell-types implicating post
      initiation translational repression mechanisms in the block to RGC-32 protein
      production in latency I cells. In summary, our results are the first to
      demonstrate RGC-32 protein upregulation in cells transformed by a human tumour
      virus and to identify post-initiation translational mechanisms as an expression
      control point for this key cell-cycle regulator.

PMID- 22163050
TI  - Phages bearing affinity peptides to bovine rotavirus differentiate the virus from
      other viruses.
AB  - The aim of this study was to identify potential ligands and develop a novel
      diagnostic test to pathogenic bovine rotavirus (BRV) using phage display
      technology. The viruses were used as an immobilized target followed by incubation
      with a 12-mer phage display random peptide library. After five rounds of
      biopanning, phages had a specific binding activity to BRV were isolated. DNA
      sequencing indicated that phage displayed peptides HVHPPLRPHSDK, HATNHLPTPHNR or
      YPTHHAHTTPVR were potential ligands to BRV. Using the specific peptide-expressing
      phages, we developed a phage-based ELISA to differentiate BRV from other viruses.
      Compared with quantitative real-time PCR (qPCR), the phage-mediated ELISA was
      more suitable for the capture of BRV and the detection limitation of this
      approach was 0.1 ug/ml of samples. The high sensitivity, specificity and low
      cross-reactivity for the phage-based ELISA were confirmed in receiver operating
      characteristics (ROC) analysis.

PMID- 22163049
TI  - Modulation of thyroid hormone-dependent gene expression in Xenopus laevis by
      INhibitor of Growth (ING) proteins.
AB  - BACKGROUND: INhibitor of Growth (ING) proteins belong to a large family of plant
      homeodomain finger-containing proteins important in epigenetic regulation and
      carcinogenesis. We have previously shown that ING1 and ING2 expression is
      regulated by thyroid hormone (TH) during metamorphosis of the Xenopus laevis
      tadpole. The present study investigates the possibility that ING proteins
      modulate TH action. METHODOLOGY/PRINCIPAL FINDINGS: Tadpoles expressing a Xenopus
      ING2 transgene (Trans(ING2)) were significantly smaller than tadpoles not
      expressing the transgene (Trans(GFP)). When exposed to 10 nM 3,5,3'
      triiodothyronine (T(3)), premetamorphic Trans(ING2) tadpoles exhibited a greater
      reduction in tail, head, and brain areas, and a protrusion of the lower jaw than
      T(3)-treated Trans(GFP) tadpoles. Quantitative real time polymerase chain
      reaction (QPCR) demonstrated elevated TH receptor beta (TRbeta) and TH/bZIP
      transcript levels in Trans(ING2) tadpole tails compared to Trans(GFP) tadpoles
      while TRalpha mRNAs were unaffected. In contrast, no difference in TRalpha,
      TRbeta or insulin-like growth factor (IGF2) mRNA abundance was observed in the
      brain between Trans(ING2) and Trans(GFP) tadpoles. All of these transcripts,
      except for TRalpha mRNA in the brain, were inducible by the hormone in both
      tissues. Oocyte transcription assays indicated that ING proteins enhanced TR
      dependent, T(3)-induced TRbeta gene promoter activity. Examination of endogenous
      T(3)-responsive promoters (TRbeta and TH/bZIP) in the tail by chromatin
      immunoprecipitation assays showed that ING proteins were recruited to TRE
      containing regions in T(3)-dependent and independent ways, respectively.
      Moreover, ING and TR proteins coimmunoprecipitated from tail protein homogenates
      derived from metamorphic climax animals. CONCLUSIONS/SIGNIFICANCE: We show for
      the first time that ING proteins modulate TH-dependent responses, thus revealing
      a novel role for ING proteins in hormone signaling. This has important
      implications for understanding hormone influenced disease states and suggests
      that the induction of ING proteins may facilitate TR function during
      metamorphosis in a tissue-specific manner.

PMID- 22163051
TI  - Cannabidiol reduces Abeta-induced neuroinflammation and promotes hippocampal
      neurogenesis through PPARgamma involvement.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been reported to
      be involved in the etiology of pathological features of Alzheimer's disease (AD).
      Cannabidiol (CBD), a Cannabis derivative devoid of psychomimetic effects, has
      attracted much attention because of its promising neuroprotective properties in
      rat AD models, even though the mechanism responsible for such actions remains
      unknown. This study was aimed at exploring whether CBD effects could be
      subordinate to its activity at PPARgamma, which has been recently indicated as
      its putative binding site. CBD actions on beta-amyloid-induced neurotoxicity in
      rat AD models, either in presence or absence of PPAR antagonists were
      investigated. Results showed that the blockade of PPARgamma was able to
      significantly blunt CBD effects on reactive gliosis and subsequently on neuronal
      damage. Moreover, due to its interaction at PPARgamma, CBD was observed to
      stimulate hippocampal neurogenesis. All these findings report the inescapable
      role of this receptor in mediating CBD actions, here reported.

PMID- 22163052
TI  - Generation of ESTs for flowering gene discovery and SSR marker development in
      upland cotton.
AB  - BACKGROUND: Upland cotton, Gossypium hirsutum L., is one of the world's most
      important economic crops. In the absence of the entire genomic sequence, a large
      number of expressed sequence tag (EST) resources of upland cotton have been
      generated and used in several studies. However, information about the flower
      development of this species is rare. METHODOLOGY/PRINCIPAL FINDINGS: To clarify
      the molecular mechanism of flower development in upland cotton, 22,915 high
      quality ESTs were generated and assembled into 14,373 unique sequences consisting
      of 4,563 contigs and 9,810 singletons from a normalized and full-length cDNA
      library constructed from pooled RNA isolated from shoot apexes, squares, and
      flowers. Comparative analysis indicated that 5,352 unique sequences had no high
      degree matches to the cotton public database. Functional annotation showed that
      several upland cotton homologs with flowering-related genes were identified in
      our library. The majority of these genes were specifically expressed in flowering
      related tissues. Three GhSEP (G. hirsutum L. SEPALLATA) genes determining floral
      organ development were cloned, and quantitative real-time PCR (qRT-PCR) revealed
      that these genes were expressed preferentially in squares or flowers.
      Furthermore, 670 new putative microsatellites with flanking sequences sufficient
      for primer design were identified from the 645 unigenes. Twenty-five EST-simple
      sequence repeats were randomly selected for validation and transferability
      testing in 17 Gossypium species. Of these, 23 were identified as true-to-type
      simple sequence repeat loci and were highly transferable among Gossypium species.
      CONCLUSIONS/SIGNIFICANCE: A high-quality, normalized, full-length cDNA library
      with a total of 14,373 unique ESTs was generated to provide sequence information
      for gene discovery and marker development related to upland cotton flower
      development. These EST resources form a valuable foundation for gene expression
      profiling analysis, functional analysis of newly discovered genes, genetic
      linkage, and quantitative trait loci analysis.

PMID- 22163053
TI  - Impact of human management on the genetic variation of wild pepper, Capsicum
      annuum var. glabriusculum.
AB  - Management of wild peppers in Mexico has occurred for a long time without clear
      phenotypic signs of domestication. However, pre-domestication management could
      have implications for the population's genetic richness. To test this hypothesis
      we analysed 27 wild (W), let standing (LS) and cultivated (C) populations, plus 7
      samples from local markets (LM), with nine polymorphic microsatellite markers.
      Two hundred and fifty two alleles were identified, averaging 28 per locus. Allele
      number was higher in W, and 15 and 40% less in LS and C populations,
      respectively. Genetic variation had a significant population structure. In W
      populations, structure was associated with ecological and geographic areas
      according to isolation by distance. When LM and C populations where included in
      the analysis, differentiation was no longer apparent. Most LM were related to
      distant populations from Sierra Madre Oriental, which represents their probable
      origin. Historical demography shows a recent decline in all W populations. Thus,
      pre-domestication human management is associated with a significant reduction of
      genetic diversity and with a loss of differentiation suggesting movement among
      regions by man. Measures to conserve wild and managed populations should be
      implemented to maintain the source and the architecture of genetic variation in
      this important crop relative.

PMID- 22163054
TI  - Stroke Genetics Update: 2011.
AB  - Although stroke remains a leading cause of disability and mortality worldwide,
      recently there have been significant advances related to our understanding of the
      genetic basis of stroke. Ongoing research efforts put us on the cusp for major
      breakthroughs in the field. In this review, we present the substantial evidence
      for the contribution of genetic variation to the development of stroke, and the
      difficulties posed in the study of stroke given the numerous genetically driven
      risk factors and stroke subtypes. We emphasize recent findings implementing
      candidate gene and genome-wide association approaches. We then discuss how
      emerging knowledge is informing and reshaping our understanding of stroke biology
      and how, in the near term, genetics may be used clinically to identify
      individuals who are at risk of disease or who may derive benefit from specific
      treatment modalities. Lastly, we address ongoing and future approaches that will
      continue to improve our understanding of stroke genetics.

PMID- 22163055
TI  - Effects of a Structured Decoding Curriculum on Adult Literacy Learners' Reading
      Development.
AB  - This article reports the results from a randomized control field trial that
      investigated the impact of an enhanced decoding and spelling curriculum on the
      development of adult basic education (ABE) learners' reading skills. Sixteen ABE
      programs that offered class-based instruction to Low-Intermediate level learners
      were randomly assigned to either the treatment group or the control group.
      Reading instructors in the 8 treatment programs taught decoding and spelling
      using the study-developed curriculum, Making Sense of Decoding and Spelling
      (MSDS), and instructors in the 8 control programs used their existing reading
      instruction. A comparison group of 7 ABE programs whose instructors used K-3
      structured curricula adapted for use with ABE learners were included for
      supplemental analyses. Seventy-one reading classes, 34 instructors, and 349 adult
      learners with pre- and posttests participated in the study. The study found a
      small but significant effect on one measure of decoding skills, which was the
      proximal target of the curriculum. No overall significant effects were found for
      word recognition, spelling, fluency, or comprehension. Pretest to posttest gains
      for word recognition were small to moderate, but not significantly better than
      the control classes. Adult learners who were born and educated outside of the
      U.S. made larger gains on 7 of the 11 reading measures than learners who were
      born and educated within the U.S. However, participation in the treatment
      curriculum was more beneficial for learners who were born and educated in the
      U.S. in developing their word recognition skills.

PMID- 22163056
TI  - Examining the relationship between urogenital schistosomiasis and HIV infection.
AB  - BACKGROUND: Urogenital schistosomiasis, caused by infection with Schistosoma
      haematobium, is widespread and causes substantial morbidity on the African
      continent. The infection has been suggested as an unrecognized risk factor for
      incident HIV infection. Current guidelines recommend preventive chemotherapy,
      using praziquantel as a public health tool, to avert morbidity due to
      schistosomiasis. In individuals of reproductive age, urogenital schistosomiasis
      remains highly prevalent and, likely, underdiagnosed. This comprehensive
      literature review was undertaken to examine the evidence for a cause-effect
      relationship between urogenital schistosomiasis and HIV/AIDS. The review aims to
      support discussions of urogenital schistosomiasis as a neglected yet urgent
      public health challenge. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a
      systematic search of the literature including online databases, clinical
      guidelines, and current medical textbooks. We describe plausible local and
      systemic mechanisms by which Schistosoma haematobium infection could increase the
      risk of HIV acquisition in both women and men. We also detail the effects of S.
      haematobium infection on the progression and transmissibility of HIV in co
      infected individuals. We briefly summarize available evidence on the
      immunomodulatory effects of chronic schistosomiasis and the implications this
      might have for populations at high risk of both schistosomiasis and HIV.
      CONCLUSIONS/SIGNIFICANCE: Studies support the hypothesis that urogenital
      schistosomiasis in women and men constitutes a significant risk factor for HIV
      acquisition due both to local genital tract and global immunological effects. In
      those who become HIV-infected, schistosomal co-infection may accelerate HIV
      disease progression and facilitate viral transmission to sexual partners.
      Establishing effective prevention strategies using praziquantel, including better
      definition of treatment age, duration, and frequency of treatment for urogenital
      schistosomiasis, is an important public health priority. Our findings call
      attention to this pressing yet neglected public health issue and the potential
      added benefit of scaling up coverage of schistosomal treatment for populations in
      whom HIV infection is prevalent.

PMID- 22163057
TI  - Utility of the tourniquet test and the white blood cell count to differentiate
      dengue among acute febrile illnesses in the emergency room.
AB  - Dengue often presents with non-specific clinical signs, and given the current
      paucity of accurate, rapid diagnostic laboratory tests, identifying easily
      obtainable bedside markers of dengue remains a priority. Previous studies in
      febrile Asian children have suggested that the combination of a positive
      tourniquet test (TT) and leucopenia can distinguish dengue from other febrile
      illnesses, but little data exists on the usefulness of these tests in adults or
      in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia
      (white blood cell count <5000/mm(3)) in identifying dengue as part of an acute
      febrile illness (AFI) surveillance study conducted in the Emergency Department of
      Saint Luke's Hospital in Ponce, Puerto Rico. From September to December 2009, 284
      patients presenting to the ED with fever for 2-7 days and no identified source
      were enrolled. Participants were tested for influenza, dengue, leptospirosis and
      enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had
      dengue co-infection with influenza and leptospirosis, respectively. An infectious
      etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary
      tract infections), and 110 patients had no infectious etiology identified. Fifty
      two percent of laboratory-positive dengue cases had a positive TT versus 18% of
      patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non
      dengue cases had leucopenia (P<0.001). The presence of either a positive TT or
      leucopenia correctly identified 94% of dengue patients. The specificity and
      positive predictive values of these tests was significantly higher in the subset
      of patients without pandemic influenza A H1N1, suggesting improved discriminatory
      performance of these tests in the absence of concurrent dengue and influenza
      outbreaks. However, even during simultaneous AFI outbreaks, the absence of
      leucopenia combined with a negative tourniquet test may be useful to rule out
      dengue.

PMID- 22163058
TI  - Tissue tropism and target cells of NSs-deleted rift valley fever virus in live
      immunodeficient mice.
AB  - BACKGROUND: Rift Valley fever virus (RVFV) causes disease in livestock and
      humans. It can be transmitted by mosquitoes, inhalation or physical contact with
      the body fluids of infected animals. Severe clinical cases are characterized by
      acute hepatitis with hemorrhage, meningoencephalitis and/or retinitis. The
      dynamics of RVFV infection and the cell types infected in vivo are poorly
      understood. METHODOLOGY/PRINCIPAL FINDINGS: RVFV strains expressing humanized
      Renilla luciferase (hRLuc) or green fluorescent protein (GFP) were generated and
      inoculated to susceptible Ifnar1-deficient mice. We investigated the tissue
      tropism in these mice and the nature of the target cells in vivo using whole
      organ imaging and flow cytometry. After intraperitoneal inoculation, hRLuc signal
      was observed primarily in the thymus, spleen and liver. Macrophages infiltrating
      various tissues, in particular the adipose tissue surrounding the pancreas also
      expressed the virus. The liver rapidly turned into the major luminescent organ
      and the mice succumbed to severe hepatitis. The brain remained weakly luminescent
      throughout infection. FACS analysis in RVFV-GFP-infected mice showed that the
      macrophages, dendritic cells and granulocytes were main target cells for RVFV.
      The crucial role of cells of the monocyte/macrophage/dendritic lineage during
      RVFV infection was confirmed by the slower viral dissemination, decrease in RVFV
      titers in blood, and prolonged survival of macrophage- and dendritic cell
      depleted mice following treatment with clodronate liposomes. Upon dermal and
      nasal inoculations, the viral dissemination was primarily observed in the lymph
      node draining the injected ear and in the lungs respectively, with a significant
      increase in survival time. CONCLUSIONS/SIGNIFICANCE: These findings reveal the
      high levels of phagocytic cells harboring RVFV during viral infection in Ifnar1
      deficient mice. They demonstrate that bioluminescent and fluorescent viruses can
      shed new light into the pathogenesis of RVFV infection.

PMID- 22163059
TI  - Genetic knockdown and pharmacological inhibition of parasite multidrug resistance
      transporters disrupts egg production in Schistosoma mansoni.
AB  - P-glycoprotein (Pgp) and multidrug resistance-associated proteins (MRPs) are ATP
      dependent transporters involved in efflux of toxins and xenobiotics from cells.
      When overexpressed, these transporters can mediate multidrug resistance (MDR) in
      mammalian cells, and changes in Pgp expression and sequence are associated with
      drug resistance in helminths. In addition to the role they play in drug efflux,
      MDR transporters are essential components of normal cellular physiology, and
      targeting them may prove a useful strategy for development of new therapeutics or
      of compounds that enhance the efficacy of current anthelmintics. We previously
      showed that expression of Schistosoma mansoni MDR transporters increases in
      response to praziquantel (PZQ), the current drug of choice against
      schistosomiasis, and that reduced PZQ sensitivity correlates with higher levels
      of these parasite transporters. We have also shown that PZQ inhibits transport by
      SMDR2, a Pgp orthologue from S. mansoni, and that PZQ is a likely substrate of
      SMDR2. Here, we examine the physiological roles of SMDR2 and SmMRP1 (the S.
      mansoni orthologue of MRP1) in S. mansoni adults, using RNAi to knock down
      expression, and pharmacological agents to inhibit transporter function. We find
      that both types of treatments disrupt parasite egg deposition by worms in
      culture. Furthermore, administration of different MDR inhibitors to S. mansoni
      infected mice results in a reduction in egg burden in host liver. These
      schistosome MDR transporters therefore appear to play essential roles in parasite
      egg production, and can be targeted genetically and pharmacologically. Since eggs
      are responsible for the major pathophysiological consequences of schistosomiasis,
      and since they are also the agents for transmission of the disease, these results
      suggest a potential strategy for reducing disease pathology and spread.

PMID- 22163061
TI  - Functional regression via variational Bayes.
AB  - We introduce variational Bayes methods for fast approximate inference in
      functional regression analysis. Both the standard cross-sectional and the
      increasingly common longitudinal settings are treated. The methodology allows
      Bayesian functional regression analyses to be conducted without the computational
      overhead of Monte Carlo methods. Confidence intervals of the model parameters are
      obtained both using the approximate variational approach and nonparametric
      resampling of clusters. The latter approach is possible because our variational
      Bayes functional regression approach is computationally efficient. A simulation
      study indicates that variational Bayes is highly accurate in estimating the
      parameters of interest and in approximating the Markov chain Monte Carlo-sampled
      joint posterior distribution of the model parameters. The methods apply
      generally, but are motivated by a longitudinal neuroimaging study of multiple
      sclerosis patients. Code used in simulations is made available as a web
      supplement.

PMID- 22163062
TI  - Verification of the genomic identity of candidate microchimeric cells.
AB  - Microchimerism has been studied in the context of a variety of diseases which
      include autoimmune diseases (such as systemic sclerosis, rheumatoid arthritis,
      systemic lupus erythematosus and autoimmune thyroid diseases), cancer (e.g., of
      the cervix, thyroid gland, lung, breast), tissue repair, transplantation and
      transfusion. It may become relevant in the context of cell-based non-invasive
      prenatal diagnosis. But how to safely identify individual microchimeric cells?
      This is a nontrivial question, for which a solution has recently been suggested. 

PMID- 22163060
TI  - Directed evaluation of enterotoxigenic Escherichia coli autotransporter proteins
      as putative vaccine candidates.
AB  - BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a major diarrheal pathogen
      in developing countries, where it accounts for millions of infections and
      hundreds of thousands of deaths annually. While vaccine development to prevent
      diarrheal illness due to ETEC is feasible, extensive effort is needed to identify
      conserved antigenic targets. Pathogenic Escherichia coli, including ETEC, use the
      autotransporter (AT) secretion mechanism to export virulence factors. AT proteins
      are comprised of a highly conserved carboxy terminal outer membrane beta barrel
      and a surface-exposed amino terminal passenger domain. Recent immunoproteomic
      studies suggesting that multiple autotransporter passenger domains are recognized
      during ETEC infection prompted the present studies. METHODOLOGY: Available ETEC
      genomes were examined to identify AT coding sequences present in pathogenic
      isolates, but not in the commensal E. coli HS strain. Passenger domains of the
      corresponding autotransporters were cloned and expressed as recombinant antigens,
      and the immune response to these proteins was then examined using convalescent
      sera from patients and experimentally infected mice. PRINCIPAL FINDINGS:
      Potential AT genes shared by ETEC strains, but absent in the E. coli commensal HS
      strain were identified. Recombinant passenger domains derived from
      autotransporters, including Ag43 and an AT designated pAT, were recognized by
      antibodies from mice following intestinal challenge with H10407, and both Ag43
      and pAT were identified on the surface of ETEC by flow cytometry. Likewise,
      convalescent sera from patients with ETEC diarrhea recognized Ag43 and pAT,
      suggesting that these proteins are expressed during both experimental and
      naturally occurring ETEC infections and that they are immunogenic. Vaccination of
      mice with recombinant passenger domains from either pAT or Ag43 afforded
      protection against intestinal colonization with ETEC. CONCLUSIONS: Passenger
      domains of conserved autotransporter proteins could contribute to protective
      immune responses that develop following infection with ETEC, and these antigens
      consequently represent potential targets to explore in vaccine development.

PMID- 22163063
TI  - The role of pDC, recipient T(reg) and donor T(reg) in HSC engraftment: Mechanisms
      of facilitation.
AB  - Hematopoietic stem cell transplantation (HSCT) has been utilized for treatment of
      many hematologic malignancies, genetic and metabolic disorders, and
      hemoglobinopathies such as sickle cell disease and thalassemia. It also induces
      donor-specific tolerance to organ and tissue transplants. The widespread success
      of HSCT is hampered by the toxicities of immunosuppression and development of
      graft-versus-host disease (GVHD). The mechanism of induction of transplantation
      tolerance (reciprocal donor/host) is still an elusive challenge in allogeneic
      HSCT. An understanding of the mechanisms for induction of tolerance and the
      critical cells involved in this process has resulted in novel cell-based
      therapies poised to be translated to clinical application. The focus of this
      review is those cells of interest.Bone marrow-derived plasmacytoid dendritic
      cells induce naive T cells to differentiate to become antigen-specific regulatory
      T cells (T(reg)), creating a milieu for the induction of transplantation
      tolerance. Recently, CD8(+)/TCR(-) facilitating cells (FC), a novel cell
      population in mouse bone marrow, have been shown to potently enhance engraftment
      of allogeneic HSC without causing GVHD. The predominant subpopulation of FC
      resembles plasmacytoid precursor dendritic cells. FC induce antigen-specific
      T(reg) in vivo. Notably, FC address one major concern that has prevented the
      implementation of T(reg) cell therapy in the clinic: to expand T(reg) and have
      them remain tolerogenic in vivo. FC are novel in that they induce an antigen
      specific regulatory milieu in vivo. The discovery of FC has opened new
      alternatives to expanded criteria in bone marrow transplantation that were
      previously restricted to human leukocyte antigen-matched recipients. The focus of
      this review is to cover what is currently known about the mechanism of FC action
      in inducing tolerance and preventing GVHD and hostversus-graft reactivity. 

PMID- 22163064
TI  - Can maternal microchimeric cells influence the fetal response toward self
      antigens?
AB  - The origins of autoimmunity are still elusive despite significant advances in
      immunology. There is cumulative evidence that, beyond simple genetics, the
      maternal environment plays a critical role in the development of common
      autoimmune disorders, such as multiple sclerosis or diabetes. In recent years,
      the trafficking of maternal cells to the offspring has been clearly demonstrated.
      This microchimerism represents the very first immunological event in fetal life.
      The number of persisting maternal cells has been associated with several
      autoimmune disorders such as systemic sclerosis, juvenile dermatomyositis and
      diabetes. The precise role of the maternal cells in these disorders remains
      unclear. Based on recent experimental work in an animal model of juvenile
      diabetes, we will discuss the possibility of maternal cells modifying the
      response of the developing fetal immunity towards self. 

PMID- 22163065
TI  - Correlation between post transplant maternal microchimerism and tolerance across
      MHC barriers in mice.
AB  - Exposure to non-inherited maternal antigens (NIMA) during fetal and neonatal life
      can result in lifelong maternal microchimerism (MMc) and tolerance to NIMA(+)
      allografts. We have previously shown that 40-50% of BDF1 female x B6 male
      offspring have multi-organ and multi-lineage MMc, while 70% have evidence of
      acquired maternal class I antigen in circulating PBMC and splenocytes. These
      features correlated with the presence of NIMA(d)-specific CD4(+) Treg cells,
      while offspring lacking MMc also lacked NIMA-specific Tregs. Furthermore, after a
      DBA/2 heart transplant, NIMA(d)-specific CD4(+) Treg cells rapidly mobilize to
      the allograft where they produce IL10 and TGFbeta, suppressing early acute
      rejection, while mice deficient in MMc and NIMA(d)-specific Treg reject, allowing
      IFNgamma-producing T effector cells to predominate in the grafts. We hypothesized
      that maternal cells occupy key sites of alloantigen presentation after
      transplant, sustaining pre-existing host Treg amidst a rising tide of donor
      alloantigen released from the graft. Using quantitative PCR to detect GFP
      transgeneic maternal cells, we found that transplant tolerance was associated
      with elevated MMc levels in blood, heart & lung, but surprisingly, not in liver.
      Rejection was associated with significantly lower levels of MMc in CD11b(+) (p =
      0.0001) and CD11c(+) (p = 0.045) splenocytes, but not with differences in T cell
      MMc. Furthermore, compared with low pre-transplant baseline rate of maternal
      antigen acquisition, long-term graft survival was associated with an increased
      mean % of cells in blood [0.5% pre vs. 5.0% post] and spleen that were dimly
      positive for H-2K(d), indicative of de novo cell-surface alloantigen acquisition
      from the DBA/2 donor heart allograft. In contrast, NIMA-exposed mice that
      rejected their DBA/2 graft showed a transient increase in H-2K(d-dim) cells in
      blood during rejection (day 9-12) but a complete absence of donor MHC acquisition
      100 days after transplant. As was the case prior to transplant, antigen
      acquisition was largely confined to MHC class II+ professional APC. CONCLUSION:
      When a NIMA-expressing organ allograft is accepted, MMc persists, mainly
      distributed into the antigen-presenting cell compartment, where the bulk of graft
      derived alloantigen for "semi-direct" presentation is also present.

PMID- 22163066
TI  - Pregnancy and the risk of autoimmune disease: An exploration.
AB  - Fetal microchimerism is the study of persisting fetal cells in the mother years
      after pregnancy and the purported implications for her health and longevity. Due
      to the association between pregnancy and autoimmune disease (AID), and the
      preponderance of these diseases in women, laboratory studies have for years
      attempted to link microchimeric fetal cells with the onset of AID after
      pregnancy. This new study gave us the opportunity to examine for the first time
      if this theory could be proven clinically in a large cohort of women. By
      examining whether different types of delivery affected the onset of AID, we also
      aimed to indirectly relate this finding to fetal microchimerism. The results did
      suggest an association between pregnancy and the risk of subsequent maternal AID,
      with increased risks noted after caesarean section (CS) and decreased risks after
      abortion. This is the first epidemiological study on the risk of AID following
      pregnancy. 

PMID- 22163067
TI  - Cadaveric bone marrow as potential source of hematopoietic stem cells for
      transplantation.
AB  - Every year, bone marrow transplantation saves many lives worldwide.
      Unfortunately, a suitable donor is not always available. Since organs are
      routinely harvested from cadaveric organ donors, we decided to assess such a
      possibility for bone marrow. We analyzed the functional properties and phenotypic
      markers of murine hematopoietic stem and progenitor cells (HSPC) from cadaveric
      bone marrow and during storage in vitro in a suspension. It was demonstrated that
      HSPC exposed to a warm or cold ischemia in intact femur did not lose their
      phenotype and maintained their repopulating ability for two to twelve hours
      depending on the temperature. Additionally, fresh bone marrow remained fully
      viable in cell suspension for two days or four days at 37 degrees C or 4 degrees
      C, respectively. Based on these findings, cadaveric bone marrow could be
      considered as an alternative source of hematopoietic stem cells for
      transplantation. 

PMID- 22163068
TI  - Covariate-adjusted nonparametric analysis of magnetic resonance images using
      Markov chain Monte Carlo.
AB  - Permutation tests are useful for drawing inferences from imaging data because of
      their flexibility and ability to capture features of the brain under minimal
      assumptions. However, most implementations of permutation tests ignore important
      confounding covariates. To employ covariate control in a nonparametric setting we
      have developed a Markov chain Monte Carlo (MCMC) algorithm for conditional
      permutation testing using propensity scores. We present the first use of this
      methodology for imaging data. Our MCMC algorithm is an extension of algorithms
      developed to approximate exact conditional probabilities in contingency tables,
      logit, and log-linear models. An application of our nonparametric method to
      remove potential bias due to the observed covariates is presented.

PMID- 22163069
TI  - Quantum Mechanical/Molecular Mechanical Study of the HDV Ribozyme: Impact of the
      Catalytic Metal Ion on the Mechanism.
AB  - A recent crystal structure of the precleaved HDV ribozyme along with biochemical
      data support a mechanism for phosphodiester bond self-cleavage in which C75 acts
      as a general acid and bound Mg(2+) ion acts as a Lewis acid. Herein this
      precleaved crystal structure is used as the basis for quantum
      mechanical/molecular mechanical calculations. These calculations indicate that
      the self-cleavage reaction is concerted with a phosphorane-like transition state
      when a divalent ion, Mg(2+) or Ca(2+), is bound at the catalytic site but is
      sequential with a phosphorane intermediate when a monovalent ion, such as Na(+),
      is at this site. Electrostatic potential calculations suggest that the divalent
      metal ion at the catalytic site lowers the pK(a) of C75, leading to the concerted
      mechanism in which the proton is partially transferred to the leaving group in
      the phosphorane-like transition state. These observations are consistent with
      experimental data, including pK(a) measurements, reaction kinetics, and proton
      inventories with divalent and monovalent ions.

PMID- 22163070
TI  - Abnormal cholesterol is associated with prefrontal white matter abnormalities
      among obese adults, a diffusion tensor imaging study.
AB  - The brain is the most cholesterol-rich organ in the body. Although most of the
      cholesterol in the brain is produced endogenously, some studies suggest that
      systemic cholesterol may be able to enter the brain. We investigated whether
      abnormal cholesterol profiles correlated with diffusion-tensor-imaging-based
      estimates of white matter microstructural integrity of lean and overweight/obese
      (o/o) adults. Twenty-two lean and 39 obese adults underwent magnetic resonance
      imaging, kept a 3-day food diary, and had a standardized assessment of fasting
      blood lipids. The lean group ate less cholesterol rich food than o/o although
      both groups ate equivalent servings of food per day. Voxelwise correlational
      analyses controlling for age, diabetes, and white matter hyperintensities,
      resulted in two significant clusters of negative associations between abnormal
      cholesterol profile and fractional anisotropy, located in the left and right
      prefrontal lobes. When the groups were split, the lean subjects showed no
      associations, whereas the o/o group expanded the association to three significant
      clusters, still in the frontal lobes. These findings suggest that cholesterol
      profile abnormalities may explain some of the reductions in white matter
      microstructural integrity that are reported in obesity.

PMID- 22163072
TI  - Chemical synthesis and functionalization of clickable
      glycosylphosphatidylinositol anchors.
AB  - Glycosylphosphatidylinositol (GPI) anchorage is a common posttranslational
      modification of eukaryotic proteins. Chemical synthesis of structurally defined
      GPIs and GPI derivatives is a necessary step toward understanding the properties
      and functions of these molecules in biological systems. In this work, the
      synthesis of several functionalized GPI anchors was accomplished using the para
      methoxybenzyl (PMB) group for permanent hydroxyl protection, which allowed the
      incorporation of functionalities that are incompatible with permanent protecting
      groups traditionally used in carbohydrate synthesis. A flexible convergent
      divergent assembly strategy enabled efficient access to a diverse set of target
      structures, including "clickable" Alkynyl-GPIs 1 and 2 and Azido-GPI 3. For
      global deprotection, a one-pot reaction was employed to afford the target GPIs in
      excellent yields (85-97%). Fully deprotected clickable GPIs 2 and 3 were readily
      conjugated to imaging and affinity probes via Cu(I)-catalyzed and Cu-free strain
      promoted [3+2] cycloaddition, respectively, resulting in GPI-Fluor 4 and GPI
      Biotin 5.

PMID- 22163071
TI  - Overcoming the challenges in the effective delivery of chemotherapies to CNS
      solid tumors.
AB  - Locoregional therapies, such as surgery and intratumoral chemotherapy, do not
      effectively treat infiltrative primary CNS solid tumors and multifocal metastatic
      solid tumor disease of the CNS. It also remains a challenge to treat such CNS
      malignant solid tumor disease with systemic chemotherapies, although these lipid
      soluble small-molecule drugs demonstrate potent cytotoxicity in vitro. Even in
      the setting of a 'normalized' tumor microenvironment, small-molecule drugs do not
      accumulate to effective concentrations in the vast majority of tumor cells, which
      is due to the fact that small-molecule drugs have short blood half-lives. It has
      been recently shown that drug-conjugated spherical lipid-insoluble nanoparticles
      within the 7-10 nm size range can deliver therapeutic concentrations of drug
      fraction directly into individual tumor cells following systemic administration,
      since these functionalized particles maintain peak blood concentrations for
      several hours and are smaller than the physiologic upper limit of pore size in
      the VEGF-derived blood capillaries of solid tumors, which is approximately 12 nm.
      In this article, the physiologic and ultrastructural basis of this novel
      translational approach for the treatment of CNS, as well as non-CNS, solid
      cancers is reviewed.

PMID- 22163074
TI  - Rapid and Sensitive Detection of Troponin I-T-C Complex from Human Serum using
      Microwave-Accelerated Metal-Enhanced Fluorescence.
AB  - We present the rapid and sensitive detection of Troponin I-T-C (Tn I-T-C) complex
      from buffer and human serum samples using Microwave-Accelerated and Metal
      Enhanced Fluorescence (MA-MEF) technique, which is based on the combined use of
      low power microwave heating, silver nanoparticle films (SNFs) and fluorescence
      spectroscopy. The detection of Tn I-T-C complex from buffer solutions and human
      serum samples on SNFs was carried out using fluorescence-based immunoassays at
      room temperature (control immunoassay, 2 hour total assay time) and using low
      power microwave heating (MA-MEF-based immunoassay, 1 minute total assay time). A
      lower detection limit for Tn I-T-C complex from buffer solutions in the control
      immunoassay and MA-MEF-based immunoassay was 0.01 ng/ml and 0.005 ng/ml,
      respectively. However, the lower detection limit for Tn I-T-C complex from human
      serum in the control immunoassay was increased to 10 ng/ml. The use of MA-MEF
      technique afforded for the detection of Tn I-T-C complex from human serum samples
      in 1 min with a lower detection limit of 0.05 ng/ml.

PMID- 22163073
TI  - Distinct redox profiles of selected human prostate carcinoma cell lines:
      implications for rational design of redox therapy.
AB  - The effects of several cancer chemotherapeutic drugs and radiation are mediated,
      at least in part, by oxidative stress. To better understand this process, we
      analyzed certain biochemical properties affecting reduction-oxidation (redox)
      balance in normal prostate epithelial cells and several prostate cancer cell
      lines. Highly aggressive androgen-independent prostate cancer PC3 cells
      demonstrated significantly higher levels of total antioxidant capacity (AC) and
      intra- and extracellular glutathione (GSH)/glutathione disulfide (GSSG) ratios
      when compared with normal prostate epithelial PrEC cells. WPE1-NB26 cells, a
      prostate cancer cell line derived from immortalized RWPE1 human prostate
      epithelial cells, demonstrated significantly higher levels of total AC and intra-
      and extracellular GSH/GSSG ratios, but lower levels of intracellular reactive
      oxygen/nitrogen species and lipid peroxidation compared with RWPE1 cells. LNCaP
      C4-2 cells, a more aggressive prostate cancer derived from less aggressive
      androgen-responsive LNCaP cells, exhibited higher levels of AC and extracellular
      GSH/GSSG ratio when compared to LNCaP cells. Specific cell types showed distinct
      cytotoxic responses to redox-modulating compounds. WPE1-NB26 cells were more
      sensitive to phenethyl isothiocyanate and tumor necrosis factor (TNF) than RWPE1
      cells, while PC3 cells were more sensitive to TNF than PrEC cells. These results
      are consistent with the hypothesis that cancer cell redox state may modulate
      responses to redox-modulating therapeutic regimens. 

PMID- 22163075
TI  - Participatory Action Research in Public Mental Health and a School of Nursing:
      Qualitative Findings from an Academic-Community Partnership.
AB  - An academic-community partnership between a school of nursing (SON) at a public
      university (the University of Virginia, or UVA) and a public mental health clinic
      developed around a shared goal of finding an acceptable shared decision making
      (SDM) intervention targeting medication use by persons with serious mental
      illness. The planning meetings of the academic-community partnership were
      recorded and analyzed. Issues under the partnership process included 1) clinic
      values and priorities, 2) research agenda, 3) ground rules, and 4) communication.
      Issues under the SDM content included: 1) barriers, 2) information exchange, 3)
      positive aspects of shared decision making, and 4) technology. Using
      participatory-action research (PAR), the community clinic was able to raise
      questions and concerns throughout the process, be actively involved in research
      activities (such as identifying stakeholders and co-leading focus groups),
      participate in the reflective activities on the impact of SDM on practice and
      policy, and feel ownership of the SDM intervention.

PMID- 22163076
TI  - Meet the Executive Editor-in-Chief.

PMID- 22163077
TI  - Introduction to the third issue.

PMID- 22163078
TI  - The water method for aiding colonoscope insertion: the learning curve of an
      experienced colonoscopist.
AB  - BACKGROUND: The water method has promising features for colonoscopy but the
      learning curve to master the technique is unknown.  AIMS: To describe the
      learning phase, and pitfalls of the water method and its impact on procedural
      outcomes by an experienced colonoscopist.  DESIGN: Review of prospectively
      collected data in a performance improvement project  SETTING: endoscopy Unit at a
      VA medical center  PATIENTS: 200 consecutive veterans undergoing colonoscopy 
      METHODS: An experienced colonoscopist examined 4 consecutive groups of 25
      patients each using the water method to define the learning curve. Outcomes were
      compared to a historical cohort (n=100) examined by the same colonoscopist using
      usual air insufflation.  MAIN OUTCOME MEASURES: Intent-to-treat (ITT) cecal
      intubation rate.  RESULTS: ITT cecal intubation rate increased from 76% (first)
      to 96% (fourth quartile). Cecal intubation time in the first 2 quartiles was
      significantly longer (8.9+/-1.0 and 8.2+/-0.8 min, respectively) than that in the
      historical cohort (5.8+/-0.4 min) but decreased and became comparable to control
      values in the next 2 quartiles (7.2+/-0.9 and 6.6+/-0.6 min, respectively).
      Overall adenoma detection rate as a group (55%), compared favorably to the
      historical cohort (46%).  CONCLUSIONS: The water method is relatively easy to
      learn for an experienced colonoscopist. Mastery of the method resulted in cecal
      intubation rate and overall adenoma detection rate meeting quality performance
      standards.

PMID- 22163080
TI  - A head-to-head hands-on comparison of ERCP mechanical simulator (EMS) and Ex-vivo
      Porcine Stomach Model (PSM).
AB  - BACKGROUND: ERCP mechanical simulator (EMS) and ex-vivo porcine stomach model
      (PSM) have been described. No direct comparison was reported on endoscopists'
      perception regarding their efficacy for ERCP training  OBJECTIVE: Comparative
      assessment of EMS and PSM.  DESIGN: Questionnaire survey before and after
      practice.  SETTING: Hands-on practice workshops.  SUBJECTS: 22 endoscopists with
      prior experience in 111+/-225 (mean+/-SD) ERCP.  INTERVENTIONS: Participants
      performed scope insertion, selective bile duct cannulation with guide wire and
      insertion of a single biliary stent. Simulated fluoroscopy with external pin-hole
      camera (EMS), or with additional transillumination (PSM) was used to monitor
      exchange of accessories.  MAIN OUTCOME MEASURE: Participants rated their
      understanding and confidence before and after hands-on practice, and credibility
      of each simulator for ERCP training. Comparative efficacy of EMS and PSM for ERCP
      education was scored (1=not, 10=very) based on pre and post practice surveys:
      realism (tissue pliability, papilla anatomy, visual/cannulation realism, wire
      manipulation, simulated fluoroscopy, overall experience); usefulness (assessment
      of results, supplementing clinical experience, easy for trainees to learn new
      skills) and application (overall ease of use, prepare trainees to use real
      instrument and ease of incorporation into training).  RESULTS: Before hands-on
      practice, both EMS and PSM received high scores. After practice, there was a
      significantly greater increase in confidence score for EMS than PSM (p<0.003).
      Participants found EMS more useful for training (p=0.017).  LIMITATIONS:
      Subjective scores.  CONCLUSIONS: Based on head-to-head hands-on comparison,
      endoscopists considered both EMS and PSM credible options for improving
      understanding and supplementing clinical ERCP training. EMS is more useful for
      basic learning.

PMID- 22163079
TI  - Comparison of diagnostic accuracy of endoscopic ultrasound-guided fine-needle
      aspiration with 22- and 25-gauge needles in the same patients.
AB  - BACKGROUND: Various factors, such as the optimal number of passes, aspiration
      pressure, and the use of 19-gauge and Trucut biopsy needles, have been studied to
      improve the diagnostic accuracy of endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA). We retrospectively compared the diagnostic accuracy of EUS
      FNA between 25- and 22-gauge needles, which have been widely used recently. 
      SUBJECTS AND METHODS: The study group comprised 47 consecutive patients who
      underwent EUS-FNA with both 22- and 25-gauge needles from October 2007 through
      March 2010. Their underlying diseases were pancreatic cancer in 24 patients,
      submucosal tumors in 11, other pancreatic tumors in 4, chronic pancreatitis in 4,
      enlarged lymph nodes in 3, and gall bladder cancer in 1. Tissue specimens, which
      were pushed out of the puncture needle, were placed into physiological saline
      solution. Gray-whitish, worm-like specimens were used for histologic diagnosis.
      The remaining specimen was centrifuged, and the sediment was plated on slides and
      examined by a cytopathologist to obtain the cytologic diagnosis.  RESULTS: A
      total of 75 punctures (mean, 1.6) were performed with 25-gauge needles, and 69
      punctures (mean, 1.4) were performed with 22-gauge needles. The overall tissue
      sampling rate for cytology was 100% (47/47), which was significantly (p=0.01)
      superior to 83% (39/47) for histology. The overall diagnostic accuracy on the
      cytologic and histologic examinations was 79% (37/47) and 85% (33/39) (p=0.48).
      According to needle type, the tissue-sampling rate for cytology and histology on
      each puncture was 97% (73/75) and 56% (42/75) with 25-guage needles, and was 97%
      (67/69) and 58% (40/69) with 22-guage needles, the accuracy of cytologic
      diagnosis on each puncture was 73% (53/73) with 25-gauge needles and 66% (44/67)
      with 22-gauge needles (p=0.37); the accuracy of histologic diagnosis on each
      puncture was 60% (25/42) and 75% (30/40) (p=0.14), respectively. No patient had
      complications.  CONCLUSIONS: The tissue-sampling rate and diagnostic accuracy did
      not differ significantly between 22- and 25-gauge needles in patients with
      pancreatic or gastrointestinal diseases who underwent EUS-FNA.

PMID- 22163081
TI  - Removal of infused water predominantly during insertion (water exchange) is
      consistently associated with a greater reduction of pain score - review of
      randomized controlled trials (RCTs) of water method colonoscopy.
AB  - INTRODUCTION: Variation in the outcomes in RcTs comparing water-related methods
      and air insufflation during the insertion phase of colonoscopy raises challenging
      questions regarding the approach. This report reviews the impact of water
      exchange on the variation in attenuation of pain during colonoscopy by water
      related methods.  METHODS: Medline (2008 to 2011) searches, abstracts of the 2011
      Digestive Disease Week (DDW) and personal communications were considered to
      identify RcTs that compared water-related methods and air insufflation to aid
      insertion of the colonoscope. Results: Since 2008 nine published and one
      submitted RcTs and five abstracts of RcTs presented at the 2011 DDW have been
      identified. Thirteen RcTs (nine published, one submitted and one abstract,
      n=1850) described reduction of pain score during or after colonoscopy (eleven
      reported statistical significance); the remaining reports described lower doses
      of medication used, or lower proportion of patients experiencing severe pain in
      colonoscopy performed with water-related methods compared with air insufflation
      (Tables 1 and 2). The water-related methods notably differ in the timing of
      removal of the infused water - predominantly during insertion (water exchange)
      versus predominantly during withdrawal (water immersion). Use of water exchange
      was consistently associated with a greater attenuation of pain score in patients
      who did not receive full sedation (Table 3).  CONCLUSION: The comparative data
      reveal that a greater attenuation of pain was associated with water exchange than
      water immersion during insertion. The intriguing results should be subjected to
      further evaluation by additional RcTs to elucidate the mechanism of the pain
      alleviating impact of the water method.

PMID- 22163082
TI  - Removal of infused water predominantly during insertion (water exchange) is
      consistently associated with an increase in adenoma detection rate - review of
      data in randomized controlled trials (RCTs) of water-related methods.
AB  - INTRODUCTION: Variation in outcomes in RcTs comparing water-related methods and
      air insufflation raises challenging questions regarding the new approach. This
      report reviews impact of water exchange - simultaneous infusion and removal of
      infused water during insertion on adenoma detection rate (ADR) defined as
      proportion of patients with a least one adenoma of any size.  METHODS: Medline
      (2008-2011) searches, abstract of 2011 Digestive Disease Week (DDW) meeting and
      personal communications were considered to identify RcTs that compared water
      related methods and air insufflation to aid insertion of colonoscope.  RESULTS:
      Since 2008, eleven reports of RcTs (6 published, 1 submitted and 4 abstracts,
      n=1728) described ADR in patients randomized to be examined by air and water
      related methods. The water-related methods differed in timing of removal of the
      infused water -predominantly during insertion (water exchange) (n=825) or
      predominantly during withdrawal (water immersion) (n=903). Water immersion was
      associated with both increases and decreases in ADR compared to respective air
      method patients and the net overall change (-7%) was significant. On the other
      hand water exchange was associated with increases in ADR consistently and the net
      changes (overall, 8%; proximal overall, 11%; and proximal <10 mm, 12%) were all
      significant.  CONCLUSION: Comparative data generated the hypothesis that
      significantly larger increases in overall and proximal colon ADRs were associated
      with water exchange than water immersion or air insufflation during insertion.
      The hypothesis should be evaluated by RCTs to elucidate the mechanism of water
      exchange on adenoma detection.

PMID- 22163083
TI  - Learning and teaching the water method (with videos).
AB  - The water method is an insertion technique for colonoscopy which has recently
      become popular owing to its demonstrated ability to decrease patient pain and
      sedation requirements. This review focuses on learning and teaching the water
      method. Data from the United States and Asia suggests that trainees at all levels
      of experience can safely learn and utilize the water method. Demonstrated
      benefits in some of the reviewed studies include lessened sedation requirements,
      less pain for patients and increased cecal intubation rates in minimally sedated
      patients. These benefits are realized without compromising safety, adenoma
      detection rates, or procedure times.

PMID- 22163084
TI  - A head-to-head comparison of the water vs. air method in patients undergoing
      screening colonoscopy.
AB  - BACKGROUND: The water method facilitates colonoscope insertion in unsedated
      patients.  OBJECTIVE: To compare quality indicators in sedated veterans.  DESIGN:
      Performance improvement.  SETTING: VA endoscopy unit.  PATIENTS: 368 consecutive
      screening patients.  INTERVENTION: Air or water method assignment (high
      definition colonoscope) was based on the last digit of social security number. 
      MEASUREMENTS: Adenoma detection rate (ADR), cecal intubation rate; intubation and
      withdrawal times; sedation requirements and external pressure used.  RESULTS: ADR
      was higher with the water method (57.1% vs. 46.1%, p=0.04). After controlling for
      age, body mass index, smoking, alcohol, withdrawal time and quality of bowel
      preparation, the odds of detecting an adenoma was 81% higher with the water
      method (OR 1.81; 95% cI: 1.12-2.90). In the proximal colon ADR was higher with
      the water method (45.8% vs. 34.6%, p=0.03), including adenomas <10 mm in size
      (41.8% vs. 31.4%, p=0.04). The water method showed significantly longer cecal
      intubation time (6.9+/-0.3 vs. 5.3+/-0.3 min, p=0.0001); less external pressure
      used (11.9% vs. 28.3%, p=0.0001); lower need for additional sedation (17.5% vs.
      27.2%, p<0.03).  LIMITATIONS: Predominance of males, single unblinded endoscopist
      with high ADR.  CONCLUSIONS: The water method is an independent factor associated
      with significantly higher ADR. Replication by blinded colonoscopist(s) is
      indicated.

PMID- 22163085
TI  - Pneumoretroperitoneum, pneumomediastinum and subcutaneous emphysema after
      colorectal endoscopic submucosal dissection (ESD) with air insufflation.

PMID- 22163086
TI  - EUS-guided transgastric drainage of caudate lobe liver abscesses.

PMID- 22163087
TI  - Erratum.
AB  - [This corrects the article on p. 78 in vol. 1, PMID: 21776430.].

PMID- 22163088
TI  - Endoscopic removal of a migrated cystogastrostomy double pigtail stent through a
      pancreatico-duodenal fistula tract.
AB  - A common complication of pancreatitis is pseudocyst formation. Endoscopic
      drainage is a widely used treatment for pancreatic pseudocysts, and offers a
      definitive solution in approximately 75% of cases. Drainage-related complications
      may be related directly to the procedure or may occur later as stents and drains
      migrate or erode into adjacent structures. Procedure-related complications
      included bleeding, pancreatitis, and infection while stent-related complications
      may involve dislocation or clogging with subsequent infection. This report is the
      first description of the successful endoscopic removal of a migrated
      cystogastrostomy double pigtail stent through a pancreatico-duodenal fistula
      tract that developed more than six years after the stent was originally misplaced
      into a pseudocyst.

PMID- 22163089
TI  - Knee kinematics following acl reconstruction in females; the effect of vision on
      performance during a cutting task.
AB  - PURPOSE/BACKGROUND: Specific movement patterns have been identified as
      influential in ACL injury; however several key kinematic variables that might be
      predictive of future performance have not been fully investigated. The purpose of
      this research was to: 1) determine if subjects with ACL reconstruction display
      different displacement, velocity, and time to peak ground reaction force (GRF)
      during cutting activities than healthy subjects, 2) observe if subjects with
      visual disruption display differences in these variables, and 3) determine if
      visual disruption alters these variables in subjects with ACL reconstruction
      relative to healthy subjects. METHODS: Seventeen healthy female subjects and 17
      female subjects with unilateral ACL reconstruction (ACLR) performed 40 trials of
      a cutting movement during which knee position was measured via a 3D
      electromagnetic system. Visual conditions were randomized to disrupt vision for 1
      second as the subject began the cutting movement, or allow full vision for
      movement duration. Independent variables were lead/push off leg (ACLR limb or
      healthy non-dominant limb) and vision (disrupted or full). 2-way ANOVAs were
      utilized to determine differences between knee kinematics using dependent
      variables of displacement (m), absolute velocity (m/sec), and time to reach peak
      GRF (% of cut). RESULTS: Knee displacement was significantly less for ACLR (.76+/
      .11; .75+/-.16) than non-dominant (.85+/-.08; .87+/-.12). Knee velocity was
      significantly slower for ACLR (.81+/-.14; .84+/-.16) than non-dominant (.92+/
      .11; .97+/-.14). A significant interaction was noted for displacement and average
      velocity (p<.05). Time to reach peak GRF was significantly longer for ACLR
      (79.41+/-2.28) than non-dominant (76.65+/-4.41). CONCLUSIONS: Subjects with ACLR
      displayed less knee displacement, slower velocity, and an increased time to reach
      peak GRF relative to healthy subjects' non-dominant knee. Visual disruption
      appeared to have some effect on movement, as noted by interaction effects. These
      movement adjustments may be indicative of an altered motor program that allows
      for successful and safe task completion while reducing the forces and load on the
      knee. LEVEL OF EVIDENCE: Level 2.

PMID- 22163090
TI  - Comparison of hip and knee strength and neuromuscular activity in subjects with
      and without patellofemoral pain syndrome.
AB  - PURPOSE/BACKGROUND: Historically, patellofemoral pain syndrome (PFPS) has been
      viewed exclusively as a knee problem. Recent findings have suggested an
      association between hip muscle weakness and PFPS. Altered neuromuscular activity
      about the hip also may contribute to PFPS; however, more limited data exist
      regarding this aspect. Most prior investigations also have not concurrently
      examined hip and knee strength and neuromuscular activity in this patient
      population. Additional knowledge regarding the interaction between hip and knee
      muscle function may enhance the current understanding of PFPS. The purpose of
      this study was to compare hip and knee strength and electromyographic (EMG)
      activity in subjects with and without PFPS. METHODS: Eighteen females with PFPS
      and 18 matched controls participated in this study. First, surface EMG electrodes
      were donned on the gluteus medius, vastus medialis, and vastus lateralis.
      Strength measures then were taken for the hip abductors, hip external rotators,
      and knee extensors. Subjects completed a standardized stair-stepping task to
      quantify muscle activation amplitudes during the loading response, single leg
      stance, and preswing intervals of stair descent as well as to determine muscle
      onset timing differences between the gluteus medius and vastii muscles and
      between the vastus medialis and vastus lateralis at the beginning of stair
      descent. RESULTS: Females with PFPS demonstrated less strength of the hip
      muscles. They also generated greater EMG activity of the gluteus medius and
      vastus medialis during the loading response and single leg stance intervals of
      stair descent. No differences existed with respect to onset activation of the
      vastus medialis and vastus lateralis. All subjects had a similar delay in gluteus
      medius onset activation relative to the vastii muscles. CONCLUSION:
      Rehabilitation should focus on quadriceps and hip strengthening. Although
      clinicians have incorporated gluteus medius exercise in rehabilitation programs,
      additional attention to the external rotators may be useful. LEVEL OF EVIDENCE:
      4.

PMID- 22163091
TI  - Comparison of ankle arthrometry to stress ultrasound imaging in the assessment of
      ankle laxity in healthy adults.
AB  - PURPOSE/BACKGROUND: Ultrasonography (US) may aid the assessment of the anterior
      talofibular ligament (ATFL) injury after lateral ankle sprains by allowing the
      clinician to visualize and measure talocrural laxity. Comparison of US against
      another objective method of ankle laxity assessment, such as ankle arthrometry
      (AA), is needed. The purpose was to evaluate the relationship between the ATFL
      length measurements measured from stress US images to the inversion and anterior
      drawer displacement measured with AA in healthy subjects. METHODS: This
      descriptive laboratory study included 26 ankles from healthy subjects. The
      apparent length of the ATFL was measured using US during anterior drawer (USAD)
      and inversion (USINV) stress and the translation of the talocrural joint was
      measured using AA during anterior drawer (AAAD) and inversion (AAINV) stress.
      Percent change in length for USAD and USINV were quantified. Intraclass
      correlation coefficients and pearson product moment correlations Bland-Altman
      limits of agreement were calculated between relevant variables. RESULTS: USAD and
      USINV percent change in length were positively correlated (r = .76). Bland Altman
      analysis revealed a mean difference of 5.38 mm (95% CI: -3.5 to 12 mm) with the
      AAAD producing higher values than the USAD. No significant correlations were
      found between the US and AA variables, however the absolute AAAD and AAINV
      variables were also positively correlated (r = .61). CONCLUSIONS: The US and AA
      variables were not directly correlated when measuring inversion and anterior
      laxity in healthy ankles. Differences between the devices that may affect this
      include different rates of joint loading, patient position and method of
      assessing laxity. The AA results demonstrated greater anterior displacement.
      Results may differ in ankle injured subjects who may demonstrate increases in
      anteroposterior and inversion laxity. LEVEL OF EVIDENCE: 2b. Exploratory study in
      healthy cohort.

PMID- 22163092
TI  - Reliability of the sitting hand press-up test for identifying and quantifying the
      level of scapular medial border posterior displacement in overhead athletes.
AB  - BACKGROUND: The lack of proper scapular kinematics can limit the function of the
      entire shoulder complex.(1,3) Many forms of scapular dyskinesis have been
      proposed along with tests to measure for the position and motion associated with
      those positional and movement faults (2,4-6). While scapular internal rotation
      has been listed among the forms of scapular dyskinesis there has not been a
      reliable test documented in the literature that examines this motion. The purpose
      of this study was to determine whether an innovative scapular medial border
      posterior displacement measurement device has adequate inter-rater and intra
      rater reliability when used at rest and during the sitting hand press up test.
      METHODS: 16 male Division III baseball players free of upper limb injury for the
      previous 12 months participated in the study. Posterior scapular displacement
      measures were taken on each subject in a resting static posture and while
      performing a sitting hand press up test. Subjects were tested twice within 24
      hours by two separate examiners. Intraclass correlation coefficients (ICC) were
      calculated to determine intra-rater and inter-rater reliability. RESULTS: The
      intra-rater reliability for rater 1 was .97 (95% confidence interval [CI]= .91
      .98), for the rest position and .95 (95% CI= .86-.98) for the sitting hand press
      up position. Intra-rater reliability for rater 2 was .99 (95% CI= .97-.99) for
      the rest position and .98 (95% CI=. 95-.99) for the sitting hand press-up
      position. The ICCs for inter-rater reliability of the scapular medial border
      posterior displacement measurement in at the rest position and the sitting hand
      press-up position were .89 (95% CI= .81-.96) and .89 (95% CI= .80-.96)
      respectively. CONCLUSIONS: The findings of this study indicate that the
      measurement of medial border posterior displacement using this device
      demonstrates good to excellent inter-rater and intra-rater reliability.

PMID- 22163093
TI  - Effects of forefoot running on chronic exertional compartment syndrome: a case
      series.
AB  - INTRODUCTION: Chronic exertional compartment syndrome (CECS) is a condition that
      occurs almost exclusively with running whereby exercise increases intramuscular
      pressure compromising circulation, prohibiting muscular function, and causing
      pain in the lower leg. Currently, a lack of evidence exists for the effective
      conservative management of CECS. Altering running mechanics by adopting forefoot
      running as opposed to heel striking may assist in the treatment of CECS,
      specifically with anterior compartment symptoms. CASE DESCRIPTION: The purpose of
      this case series is to describe the outcomes for subjects with CECS through a
      systematic conservative treatment model focused on forefoot running. Subject one
      was a 21 y/o female with a 4 year history of CECS and subject two was a 21 y/o
      male, 7 months status-post two-compartment right leg fasciotomy with a return of
      symptoms and a new onset of symptoms on the contralateral side. OUTCOME: Both
      subjects modified their running technique over a period of six weeks. Kinematic
      and kinetic analysis revealed increased step rate while step length, impulse, and
      peak vertical ground reaction forces decreased. In addition, leg
      intracompartmental pressures decreased from pre-training to post-training. Within
      6 weeks of intervention subjects increased their running distance and speed
      absent of symptoms of CECS. Follow-up questionnaires were completed by the
      subjects at 7 months following intervention; subject one reported running
      distances up to 12.87 km pain-free and subject two reported running 6.44 km pain
      free consistently 3 times a week. DISCUSSION: This case series describes a
      potentially beneficial conservative management approach to CECS in the form of
      forefoot running instruction. Further research in this area is warranted to
      further explore the benefits of adopting a forefoot running technique for CECS as
      well as other musculoskeletal overuse complaints.

PMID- 22163094
TI  - Electromyographic activity of scapular muscles during diagonal patterns using
      elastic resistance and free weights.
AB  - PURPOSE/BACKGROUND: Abnormalities in glenohumeral rhythm and neuromuscular
      control of the upper trapezius (UT), middle trapezius (MT), lower trapezius (LT)
      and serratus anterior (SA) muscles have been identified in individuals with
      shoulder pain. Upper extremity diagonal or proprioceptive neuromuscular
      facilitation (PNF) patterns have been suggested as effective means of activating
      scapular muscles, yet few studies have compared muscular activation during
      diagonal patterns with varying modes of resistance. The purpose of this study is
      to determine which type of resistance and PNF pattern combination best elicits
      electromyographic (EMG) activity of the scapular muscles. METHODS: Twenty one
      healthy subjects with no history of scapulohumeral dysfunction were recruited
      from a population of convenience. Surface electrodes were applied to the SA, UT,
      MT and LT and EMG data collected for each muscle as the subject performed
      resisted UE D1 flexion, UE D1 extension, UE D2 flexion and UE D2 extension with
      elastic resistance and a three pound weight. RESULTS: No significant differences
      were found between scapular muscle activity during D1 flexion when using elastic
      resistance and when using a weight. UT, MT and LT values were also not
      significantly different during D2 flexion when using elastic resistance vs. using
      a weight. The activity of the SA remained relatively the same during all
      patterns. The LT activity was significantly greater during D2 flexion with
      elastic resistance than during the D1 flexion and D1 extension with elastic
      resistance. MT activity was significantly greater during D2 flexion with elastic
      resistance as compared to all other patterns except D2 flexion with a weight. UT
      activity was significantly greater during flexion patterns than extension
      patterns. CONCLUSIONS: The upper extremity PNF pattern did significantly affect
      the mean UT, MT and LT activity but was not found to significantly affect SA
      activity. The type of resistance did not significantly change muscle activity
      when used in the same diagonal patterns.

PMID- 22163095
TI  - The clinical utility of functional performance tests within one-year post-acl
      reconstruction: a systematic review.
AB  - INTRODUCTION: A tear of the anterior cruciate ligament (ACL) represents a
      significant injury for an athlete that requires substantial time away from sport,
      and significant rehabilitation after reconstruction. The physical therapist is
      responsible to determine when a patient is capable of tolerating the physical
      demands of daily activities and to attempt to prevent re-injury. Physical or
      functional performance tests (FPTs) are one mechanism used to evaluate the
      athlete's physical skills and capabilities prior to returning to sports
      participation. The purpose of this systematic review is to critically examine the
      clinical utility of functional performance tests used with patients less than or
      equal to one year post ACL reconstruction. METHODS: A systematic review of the
      relevant literature was performed using PRISMA guidelines. A total of twelve
      studies were included for analysis. RESULTS: Two independent blinded reviewers
      then analyzed and rated the final included articles (n=12) utilizing the
      Newcastle-Ottawa Scale (NOS). Percent overall agreement between raters for the
      NOS was 88% with a fixed-marginal kappa (kappa) of 0.80. Of the 12 included
      articles, the FPTs were utilized as an outcome measure within the study design
      (41.7%) or studied as a measure of function (58.3%). Among those studies that
      used FPTs as a "measure of function" 71.4% studied a battery of FPTs, while 28.6%
      studied a single test. None of the studies utilized FPTs as a measure to
      determine readiness to return to sport. DISCUSSION: FPTs are being utilized with
      patients, less than or equal to one year post ACL reconstruction, either as an
      assessment of functional performance or as an outcome measure. No studies
      identified a FPT or test battery that has construct or predictive validity for
      "return to sport" in athletic population one-year post-ACL reconstruction. The
      identification of the critical elements within the return to sport construct may
      allow lower extremity performance tests to be developed or test batteries
      assembled to incorporate the appropriate tests to examine all of these elements
      deemed critical. Additionally the current FPTs should undergo content and
      predictive validation to assist the sports physical therapist in determining the
      readiness of the athlete for return to sport.

PMID- 22163096
TI  - Comprehensive strength training program for a recreational senior golfer 11
      months after a rotator cuff repair.
AB  - BACKGROUND AND PURPOSE: Golf is a popular sport played by hundreds of thousands
      of individuals of all ages and of varying skill levels. An orthopedic or sports
      related injury and/or surgery may limit an individual's sport participation,
      require him/her to complete a course of rehabilitation, and initiate (or resume)
      a sport-specific training program. Unlike the availability of evidence to guide
      postsurgical rehabilitation and sport-specific training of athletes from sports
      other than golf, there have only been two reports describing outcomes after
      surgery and for golfers. The purpose of this case report is to present a post
      rehabilitation return to sport-training program for a recreational golfer 11
      months after a rotator cuff repair. CASE DESCRIPTION: The subject, a 67-year old
      female, injured her right shoulder requiring a rotator cuff repair 11-months
      prior to her participation in a golf fitness training program. The subject
      participated in six training sessions over seven week period consisting of
      general strengthening exercises (including exercises for the rotator cuff),
      exercises for the core, plyometrics, and power exercises. OUTCOMES: The subject
      made improvements in power and muscular endurance of the core. She was able to
      resume golf at the completion of the training program. DISCUSSION: The subject
      was able to make functional improvements and return to golf after participation
      in a comprehensive strength program. Additional studies are necessary to improve
      program design for golfers who wish to return to sport after shoulder surgery.

PMID- 22163097
TI  - Chest injuries, what the sports physical therapist should know.
AB  - Chest injuries in contact and collision sports are relatively rare, particularly
      those that are life threatening. However, as with every sports related injury,
      one must initially consider life threatening situations that may occur as a
      result of collision with another player, a stationary object, or being struck
      with some type of object (missile). In other words, as is the case in all acute
      sports injury assessment, the mechanism of injury must be considered when
      evaluating the injured athlete on the field as well as on the sidelines. The
      Sports Physical Therapist (PT) must look for several initial life threatening
      conditions as well as be aware of and monitor for the development of these
      symptoms during the subsequent evaluation of the athlete. The purpose of this
      clinical commentary is to review the presentation and management of several
      emergent conditions associated with injuries to the chest and thorax.

PMID- 22163098
TI  - Erratum: ERRATUM.
AB  - [This corrects the article on p. 150 in vol. 6, PMID: 21904694.].

PMID- 22163099
TI  - Grb2-associated binding (Gab) proteins in hematopoietic and immune cell biology.
AB  - Grb2-associated binding (Gab) scaffolding/adapter proteins are a family of three
      members including mammalian Gab1, Gab2, and Gab3 that are highly conserved. Since
      the discovery of these proteins, there has been an extensive amount of work done
      to better understand Gab functional roles in multiple signaling pathways,
      typically acting as a downstream effectors of receptor-tyrosine kinase (RTK)
      triggered signal transduction. In addition to their participation in
      hematopoiesis, Gabs play important roles in regulation of immune response and in
      also in cancer cell signaling. Gabs may play complex roles and thus a complete
      understanding of their interactions and how they modulate hematopoietic and
      immune cell biology remains to be determined. This review will cover the most
      recent findings including the involvement of Gabs in disease development and
      signaling which will be important for design of future therapeutic interventions.

PMID- 22163101
TI  - DIFFERENCES IN SIMULATED CAR FOLLOWING BEHAVIOR OF YOUNGER AND OLDER DRIVERS.
AB  - Older drivers are at risk for vehicle crashes due to impairments of visual
      processing and attention, placing these drivers at greater risk in driving tasks
      that require continuous attention to neighboring traffic, especially lead
      vehicles (LVs). We investigated car following behavior in 42 younger drivers
      (ages 18 to 44 years) and 58 older drivers (ages 65 to 86 years) in a driving
      simulator. The drivers were instructed to maintain two car lengths from a virtual
      LV. The LV varied its velocity according to a sum of three sine waves, making the
      velocity changes unpredictable to the drivers. A Fourier analysis was performed
      using the vehicle trajectory data to derive measures of coherence, gain, and
      delay as indices of car following behavior. These measures as well as headway
      distance were compared between the two groups. Older drivers were less able to
      match changes in the LV velocity indicated by lower coherence (0.76 v. 0.84,
      p=0.019) and larger gain (2.24 v. 1.74, p=0.031). However, these drivers followed
      further behind the LV than younger drivers, a potential compensatory strategy
      that may reduce collision risk for older drivers.

PMID- 22163100
TI  - The mesopontine rostromedial tegmental nucleus: an integrative modulator of the
      reward system.
AB  - The mesopontine rostromedial tegmental nucleus (RMTg) is a newly discovered brain
      structure thought to profoundly influence reward-related pathways. The RMTg is
      prominently GABAergic, receives dense projections from the lateral habenula and
      projects strongly to the midbrain ventral tegmental area and substantia nigra
      compacta. It receives additional afferent connections from widespread brain
      structures and sends additional strong efferent connections to a number of non
      dopaminergic brainstem structures and, to a lesser extent, the forebrain.
      Projection neurons of the RMTg have been shown to express Fos in response to
      aversive stimuli and/or reward omission and psychostimulant drug administration.
      This review will first recount how the RMTg was discovered and then describe in
      greater detail what is known about its neuroanatomical relationships, including
      afferent and efferent connections, neurotransmitters, and receptors. Finally, we
      will focus on what has been reported about its function.

PMID- 22163117
TI  - Application of a generalized scan statistic model to evaluate TOF PET images.
AB  - Noise equivalent counts (NEC) have been used as a measure or proxy of PET image
      quality for many years. It has been shown to be a useful metric, for example to
      determine clinical patient dosage. However, NEC should be used cautiously in
      evaluating image quality since it is a global data quality measure that does not
      take into account localized effects due to spatial resolution and image
      reconstruction, as well as the effect of time-of-flight (TOF) imaging on
      resultant images. In this work, we study the use of a numerical observer that
      uses a generalized scan-statistic model to estimate lesion detectability with
      localization in a uniform background phantom, for varying activity levels and
      scan times. Data were acquired on a clinical whole-body TOF PET scanner. Data
      show that ALROC increases as a function of NEC but at high activity levels it
      approaches a peak value earlier than the NEC peak. Also, the ALROC for images
      acquired with the same NEC, but at two different activity levels and scan times,
      is similar. Our results show that with TOF information we can either achieve
      improved clinical performance for heavy patients, or reduce the scan time or
      injected activity while maintaining similar ALROC value as in a Non-TOF image.

PMID- 22163118
TI  - Medical professionalism meets generation X: a perfect storm?

PMID- 22163119
TI  - A postman with polyuria.

PMID- 22163121
TI  - Cardiac surgery: a century of progress.
AB  - Well into the first decades of the 20th century, medical opinion held that any
      surgical attempts to treat heart disease were not only misguided, but unethical.
      Despite such reservations, innovative surgeons showed that heart wounds could be
      successfully repaired. Then, extracardiac procedures were performed to correct
      patent ductus arteriosus, coarctation of the aorta, and tetralogy of Fallot.
      Direct surgery on the heart was accomplished with closed commissurotomy for
      mitral stenosis. The introduction of the heart-lung machine and cardiopulmonary
      bypass enabled the surgical treatment of other congenital and acquired heart
      diseases. Advances in aortic surgery paralleled these successes. The development
      of coronary artery bypass grafting greatly aided the treatment of coronary heart
      disease. Cardiac transplantation, attempts to use the total artificial heart, and
      the application of ventricular assist devices have brought us to the present
      day.Although progress in the field of cardiovascular surgery appears to have
      slowed when compared with the halcyon times of the past, substantial challenges
      still face cardiac surgeons. It can only be hoped that sufficient resources and
      incentive can carry the triumphs of the 20th century into the 21st. This review
      covers past developments and future opportunities in cardiac surgery.

PMID- 22163120
TI  - CD34-positive stem cells: in the treatment of heart and vascular disease in human
      beings.
AB  - Bone marrow-derived CD34(+) cells are a well-characterized population of stem
      cells that have traditionally been used clinically to reconstitute the
      hematopoietic system after radiation or chemotherapy. More recently, CD34(+)
      cells have also been shown to induce therapeutic angiogenesis in animal models of
      myocardial, peripheral, and cerebral ischemia. The mechanism by which CD34(+)
      cells promote therapeutic angiogenesis is not completely understood, although
      evidence supports both direct incorporation of the cells into the expanding
      vasculature and paracrine secretion of angiogenic growth factors that support the
      developing microvasculature. Phase I and phase II clinical trials have explored
      the usefulness of CD34(+) cells in the treatment of ischemic conditions in human
      patients. As the population of patients diagnosed with some form of ischemic
      cardiovascular disease expands, the need for more effective treatments also
      grows, especially in patients who are refractory to standard pharmacologic or
      revascularization treatment. As phase III trials begin, CD34(+) cells will be
      definitively tested as a novel treatment for myocardial and peripheral ischemia.
      This review will discuss what is known about the CD34 antigen and the cells that
      harbor it, the preclinical evidence supporting the therapeutic potential of
      CD34(+) cells in ischemic models, and, last, the current evidence for the
      clinical usefulness of CD34(+) cells in the treatment of human ischemic disease.

PMID- 22163122
TI  - Mechanical behavior of fully expanded commercially available endovascular
      coronary stents.
AB  - The mechanical behavior of endovascular coronary stents influences their
      therapeutic efficacy. Through computational studies, researchers can analyze
      device performance and improve designs. We developed a 1-dimensional finite
      element method, net-based algorithm and used it to analyze the effects of radial
      loading and bending in commercially available stents. Our computational study
      included designs modeled on the Express, Cypher, Xience, and Palmaz stents.We
      found that stents that did not fully expand were less rigid than the fully
      expanded stents and, therefore, exhibited larger displacement. Stents with an
      open-cell design, such as Express-like or Xience-like stents, had a higher
      bending flexibility. Stents with in-phase circumferential rings, such as the
      Xience-like stent, had the smallest longitudinal extension when exposed to radial
      compression forces. Thus, the open-cell model that had in-phase circumferential
      rings connected by straight horizontal struts exhibited radial stiffness, bending
      flexibility, and the smallest change in stent length during radial forcing. The
      Palmaz-like stent was the most rigid of all. These findings are supported by
      clinical experience.Computer simulations of the mechanical properties of
      endovascular stents offer sophisticated insights into the mechanical behavior of
      different stent designs and should be used whenever possible to help physicians
      decide which stent is best for treating a given lesion. Our 1-dimensional finite
      element method model is incomparably simpler, faster, and more accurate than the
      classical 3-dimensional approaches. It can facilitate stent design and may aid in
      stent selection in the clinical setting.

PMID- 22163123
TI  - First human trial of KW39 slotted-tube stents: for percutaneous coronary
      intervention.
AB  - The KW39 stent is a balloon-expandable, stainless-steel, slotted-tube stent,
      newly designed to adjust to the shape of the coronary arteries. We evaluated the
      clinical efficacy and safety of KW39 stent-based percutaneous coronary
      interventions in human native coronary arteries. A total of 105 patients (110
      lesions), with a diagnosis of stable angina, acute coronary syndrome, or
      asymptomatic myocardial ischemia, were included in this prospective study. The
      primary endpoint was the target-lesion revascularization rate at the conclusion
      of a 6-month follow-up period. The secondary endpoints were the rates of
      technical and procedural success and the rate of major adverse cardiac events
      (defined as cardiac death, myocardial infarction, and target-lesion
      revascularization) in the course of the 6 months after stent placement. The 6
      month target-lesion revascularization rate was 8.6%. The KW39 stent was highly
      satisfactory in regard to all secondary endpoint comparisons. Binary (>50%) in
      stent restenosis was observed in 22 of 110 lesions (20%). The mean diameter
      stenosis at 6 months after percutaneous coronary intervention was 35.1% +/-
      14.4%, and the mean late lumen loss was 1.06 +/- 0.48 mm. Stepwise multivariate
      analysis showed probable causal associations between adverse local environments
      for stent implantation and the subsequent need for target-lesion
      revascularization. We conclude that KW39 stent implantation was technically
      feasible and clinically safe in the patient population that we studied. The
      results of the safety endpoints, including cardiac death and acute myocardial
      infarction, were acceptable.

PMID- 22163124
TI  - Sirolimus-eluting stents versus bare-metal stents in routine clinical use: a
      nonrandomized comparison.
AB  - Conflicting patient outcomes have been reported after the use of sirolimus
      eluting stents or bare-metal stents. In this nonrandomized study, we examine the
      outcomes after placement of sirolimus-eluting versus bare-metal stents in an
      unselected population of patients who underwent percutaneous coronary
      revascularization.We used THIRD-base, a longitudinal data registry of patients
      who underwent revascularization at our institution, to compare demographics and
      outcomes in patients treated with a sirolimus-eluting or bare-metal stent from
      January 2001 through June 2006. Outcome measures included major acute coronary
      and cerebral events at 30 days, target-vessel failure at 9 months and at 3 years,
      and stent thrombosis. Target-vessel failure was defined as the composite of all
      cause death, recurrent myocardial infarction in the treated vessel distribution,
      and target-vessel revascularization. Logistic regression and Cox proportional
      regression models were used to determine the predictors of outcome.Of the 6,425
      patients analyzed, 2,581 patients (40.2%) received only sirolimus-eluting stents,
      and 3,844 patients (59.8%) received only bare-metal stents. Early major acute
      coronary and cerebral events and stent thrombosis at 30 days and 9 months were
      similar in both groups. Target-vessel failure was less frequent in sirolimus
      eluting stent patients than in bare-metal stent patients at 9 months (4.84% vs
      11.81%, P < 0.0001) and at 3 years (29% vs 32%, P < 0.0001).Use of sirolimus
      eluting stents improved target-vessel failure survival at 9 months and at 3
      years. Late adverse events were determined by known risk factors for
      atherosclerosis, not by stent type.

PMID- 22163125
TI  - The role of von Willebrand factor and ADAMTS13 in the no-reflow phenomenon: after
      primary percutaneous coronary intervention.
AB  - We prospectively studied the correlations between plasma levels of von Willebrand
      factor and its cleaving protease--a disintegrin and metalloproteinase with
      thrombospondin type I motif, member 13 (ADAMTS13)--in 126 patients who did or did
      not develop no-reflow phenomenon after primary percutaneous intervention for
      acute ST-segment-elevation myocardial infarction. Quantitative plasma levels of
      von Willebrand factor and ADAMTS13 were measured by immunoturbidometric
      assay.Angiographic no-reflow was observed in 46 (37%) of the 126 patients. At
      admission, plasma levels of von Willebrand factor were significantly higher in
      the no-reflow group (P < 0.001), but levels of ADAMTS13 at admission were similar
      in the 2 groups (P = 0.143). At logistic regression, after adjustment for serum
      creatinine, left ventricular ejection fraction, high-sensitivity C-reactive
      protein, and N-terminal pro B-type natriuretic peptide, plasma von Willebrand
      factor level at admission (>= 5,531 mU/mL) was still the predictive factor for
      the no-reflow phenomenon. The area under the receiver operating characteristics
      curve was 0.785.Our results suggest that high von Willebrand factor level is
      related to the no-reflow phenomenon in such a way that it might be a predictor of
      the phenomenon.

PMID- 22163126
TI  - Long-term follow-up of iatrogenic atrial septal defect: after percutaneous mitral
      balloon valvuloplasty.
AB  - During percutaneous mitral balloon valvuloplasty, the Inoue method leaves
      patients with an iatrogenic atrial septal defect. In this study, we evaluated the
      factors affecting the development of iatrogenic atrial septal defect and searched
      for the possible influence of this defect on long-term outcomes.We reviewed the
      medical records of 267 patients who had undergone successful percutaneous mitral
      balloon valvuloplasty for symptomatic moderate or severe mitral stenosis from
      January 2000 through March 2004. Sixty-three of the 267 patients were enrolled in
      a face-to-face follow-up study. We noted their clinical and demographic
      characteristics. All included patients were asked for the endpoints of repeat
      percutaneous mitral balloon valvuloplasty or mitral valve surgery,
      cerebrovascular accident or transient ischemic attack, and the need of
      intervention for the iatrogenic atrial septal defect. They underwent standard 2
      dimensional and Doppler echocardiographic examination. The presence of iatrogenic
      atrial septal defect was evaluated via the color-Doppler technique in the
      subcostal view and via contrast echocardiography.Patients were subclassified in
      accordance with the presence (n = 15) or absence (n = 48) of
      echocardiographically proven persistent iatrogenic atrial septal defect. When we
      compared the 2 groups, there were no significant differences in baseline
      demographic characteristics or in pre- and postprocedural echocardiographic
      data.We conclude that the presence of persistent iatrogenic atrial septal defects
      might not be predicted from echocardiographic or demographic data in patients
      undergoing percutaneous mitral balloon valvuloplasty. Fortunately, these defects
      are small in size and low in shunt ratio. They appear not to be associated with
      serious long-term outcomes.

PMID- 22163127
TI  - Perimembranous ventricular septal defect with aneurysm: two options for
      transcatheter closure.
AB  - We present our experience with 2 options for device closure of perimembranous
      ventricular septal defect with aneurysm. Thirty-four patients with perimembranous
      ventricular septal defect with aneurysm, aged from 14 to 42 years, underwent
      transcatheter closure with modified double-disk occluders. A sheath was used to
      deliver the occluder after establishment of a stable "arteriovenous loop" under
      fluoroscopy. Electrocardiography and transthoracic echocardiography were used for
      follow-up. All but 1 patient experienced successful transcatheter closure of
      perimembranous ventricular septal defect with aneurysm, when occluders were used
      in 2 different positions. There were 19 patients whose perimembranous ventricular
      septal defects were closed at the inlet of the aneurysm and 15 patients whose
      defects were closed at the outlet. Eight patients had a residual shunt
      immediately after the procedure, which disappeared during follow-up. One patient
      developed minor aortic regurgitation. Four patients who manifested different
      types of conductive block were all in the group that underwent closure at the
      inlet of the aneurysm. No other complications were observed during follow-up.We
      infer that perimembranous ventricular septal defect with aneurysm can be
      successfully closed with modified double-disk occluders. Each of the 2 options
      that we have presented for transcatheter closure of perimembranous ventricular
      septal defect with aneurysm has its advantages and disadvantages. Ultimately, the
      configuration of the lesion should decide the type and position of the device.

PMID- 22163128
TI  - Altered systemic ketone body metabolism in advanced heart failure.
AB  - Heart failure is a systemic disease in which both myocardium and skeletal muscle
      exhibit alterations of energy metabolism. Failing myocardium exhibits impaired
      utilization of free fatty acids and glucose, which are major substrates for
      myocardial energy production. Ketone bodies normally provide a modest
      contribution to energy balance, but serum concentrations of ketone bodies are
      elevated in heart failure. To profile ketone body metabolism in advanced heart
      failure, we directly measured ketone body utilization by heart and skeletal
      muscle.Metabolite concentrations in arterial, coronary sinus, and central venous
      beds were measured to derive myocardial and skeletal-muscle ketone body
      utilization in 11 patients with advanced heart failure and 10 healthy control
      subjects who were undergoing electrophysiologic procedures. As expected, the mean
      myocardial arteriovenous oxygen difference was significantly increased in the
      heart-failure patients (8.3 +/- 0.4 mL/dL, vs 7 +/- 0.5 mL/dL in the control
      subjects; P = 0.05). Although the mean myocardial ketone body extraction ratio
      was relatively unchanged (0.49 +/- 0.05 in heart-failure patients vs 0.54 +/-
      0.06 in control subjects, P = 0.53), skeletal-muscle ketone body utilization was
      markedly lower in the heart-failure patients (0.18 +/- 0.06, vs 0.4 +/- 0.04 in
      control subjects; P = 0.01).In this preliminary study, heart failure was
      associated with tissue-specific alteration of ketone body metabolism. In advanced
      heart failure, skeletal-muscle ketone body utilization was impaired, whereas
      myocardial ketone body utilization was preserved. Future studies are needed to
      determine whether ketone body metabolism serves as a dynamic quantitative
      biomarker of skeletal myopathy and fatigue in heart failure.

PMID- 22163129
TI  - Sudden cardiac arrest: associated with anomalous origin of the right coronary
      artery from the left main coronary artery.
AB  - Anomalous origin of the coronary artery from the opposite sinus of Valsalva and a
      course of that artery between the ascending aorta and the pulmonary artery is a
      rare congenital anomaly. It can cause myocardial ischemia, syncope, and sudden
      cardiac death in young people. Herein, we report the case of a 24-year-old man
      who was brought to our hospital after cardiac arrest due to ventricular
      fibrillation. Emergent coronary angiography revealed that the left coronary
      artery was normal; however, the right coronary artery originated at the left
      sinus of Valsalva. After admission, the patient was treated with mild therapeutic
      hypothermia for 48 hours and had a favorable neurologic recovery. Subsequent 16
      slice multidetector computed tomography revealed that the right coronary artery
      arose from the left main coronary artery, took an intramural course, and was
      severely compressed between the ascending aorta and the pulmonary artery. The
      patient underwent direct implantation of the anomalous artery into the correct
      aortic sinus. Histologic specimens from the proximal end of the right coronary
      artery showed an intramural segment with intimal fibrous thickening,
      fragmentation and random arrangement of the elastic fiber, degeneration of the
      medial smooth-muscle cells, and an increase in the medial stromal substance.
      Postoperatively, repeat coronary angiography with provocation testing for
      coronary spasm revealed no myocardial ischemic change. The patient recovered
      uneventfully. We found that cardiac multidetector computed tomography was useful
      in evaluating the cause of the sudden cardiac arrest, identifying the anomalous
      coronary artery, and helping to guide the surgical decisions.

PMID- 22163130
TI  - Sudden death and coronary anomalies: the importance of a detailed description.

PMID- 22163131
TI  - Novel single-stage operation and inflow source: for thoracic aortic aneurysm and
      limb ischemia.
AB  - Patients with thoracic aortic aneurysms sometimes also have peripheral vascular
      disease. In such cases, staged operations are usually performed in order to avoid
      additional morbidity. We have achieved good long-term outcomes in 2 patients with
      use of a single-stage surgical technique. Our novel procedure uses a pre-sewn
      side branch with a Dacron graft as the inflow source for the aortofemoral bypass
      during thoracic aortic aneurysm repair. As of 25 and 52 months' follow-up, these
      grafts were patent in our 2 patients. We believe that this procedure is a safe
      and easy single-stage operation that achieves favorable patency. To our
      knowledge, this is the first report to document the use of a pre-sewn perfusion
      branch of a Dacron graft as an inflow source for aortofemoral bypass.

PMID- 22163132
TI  - UNOS status of heart transplant patients supported with a left ventricular assist
      device: is it time to reconsider the status criteria?

PMID- 22163133
TI  - A changing trend toward destination therapy: are we treating the same patients
      differently?

PMID- 22163134
TI  - Multiple-organ transplantation from a single donor.

PMID- 22163135
TI  - Isolated type a interrupted aortic arch: in an asymptomatic 19-year-old man.
AB  - Interrupted aortic arch, characterized by luminal and anatomic discontinuity
      between the ascending and descending aorta, is a very rare congenital
      malformation. The condition is typically diagnosed in neonates and is highly
      fatal if left untreated. Herein, we report the unusual diagnosis of an isolated
      type A interrupted aortic arch in a hypertensive, asymptomatic 19-year-old man.

PMID- 22163136
TI  - Transfusion-free complex cardiac surgery: with use of deep hypothermic
      circulatory arrest in a preterm 2.96-kg Jehovah's witness neonate.
AB  - In neonates, the major obstacle to transfusion-free complex cardiac surgery is
      the severe hemodilution that can result from the mismatch between the priming
      volume of the circuit and the patients' blood volume. Herein, we report the case
      of a 13-day-old, 2.96-kg preterm neonate who had a hypoplastic aortic arch and
      atrial and ventricular septal defects. At the insistence of her Jehovah's Witness
      parents, we performed corrective surgery without transfusing homologous blood
      products--using deep hypothermic circulatory arrest in the process. A specially
      designed cardiopulmonary bypass circuit with a priming volume of only 95 mL was
      the key component of an interdisciplinary effort to avoid transfusion while
      maintaining the patient's safety. To our knowledge, this is the 1st report of the
      use of deep hypothermic circulatory arrest in blood-transfusion-free surgery to
      correct congenital heart defects in a small Jehovah's Witness neonate.

PMID- 22163137
TI  - Extracorporeal membrane oxygenation with hemoconcentration: in a hypervolemic
      patient with critical aortic stenosis.
AB  - Herein, we describe the case of a 60-year-old man with severe nonischemic
      cardiomyopathy and hypervolemia. By means of venoarterial extracorporeal membrane
      oxygenation at the bedside, along with hemoconcentration, the patient was
      resuscitated from severe cardiogenic shock and normal blood volume was restored.
      Within 24 hours, he was able to undergo a high-risk aortic valve replacement for
      severe aortic stenosis, with a successful outcome. To our knowledge, this is the
      first reported case in which hemoconcentration with extracorporeal membrane
      oxygenation has been used to support a patient with severe hypervolemia.

PMID- 22163138
TI  - Reverse takotsubo cardiomyopathy: after an episode of serotonin syndrome.
AB  - Stress-induced cardiomyopathy is characterized by transient left ventricular
      dysfunction, usually followed by complete resolution. It is precipitated by
      severe stress, and the most common variant (takotsubo) is marked by apical
      hypokinesis and ballooning with basal hyperkinesis. Serotonin syndrome is best
      understood as excess serotonergic activity in the central and peripheral nervous
      system. This imposes significant stress on the body. We report what we believe is
      the 1st case of serotonin syndrome as an indirect cause of stress-induced
      cardiomyopathy with a reverse takotsubo profile.

PMID- 22163139
TI  - Takotsubo cardiomyopathy associated with titration of duloxetine.
AB  - Takotsubo cardiomyopathy is characterized by transient multisegmental left
      ventricular dysfunction, dynamic electrocardiographic changes that mimic acute
      myocardial infarction, and the absence of obstructive coronary disease. Takotsubo
      cardiomyopathy has been solidly associated with antecedent emotional and physical
      stressors that trigger catecholamine surges, which lead to coronary vasospasm or
      direct myocardial injury. Some medications can also cause catecholamine surges,
      although this phenomenon is not as well described. Duloxetine is a combined
      serotonin and norepinephrine reuptake inhibitor (SNRI). The basic goal of SNRIs
      is to increase catecholamine levels in neuronal tissue. However, the increased
      catecholamine levels may also affect the cardiovascular system.Herein, we report
      the case of a 59-year-old woman whose takotsubo cardiomyopathy was temporally
      associated with the titration of duloxetine. The duloxetine therapy was
      subsequently discontinued, and the patient's left ventricular function recovered
      completely 1 month after the index event. The purpose of this report is to alert
      clinicians to a possible association between SNRI medications and takotsubo
      cardiomyopathy.

PMID- 22163140
TI  - Mad-honey sexual activity and acute inferior myocardial infarctions in a married
      couple.
AB  - Mad-honey poisoning can occur after the eating of honey that contains
      grayanotoxin. Mad honey is intentionally produced from the nectar of Rhododendron
      ponticum, which grows in Japan, Nepal, Brazil, parts of North America and Europe,
      and the eastern Black Sea region of Turkey. Low doses of grayanotoxin can cause
      dizziness, hypotension, and bradycardia, and high doses can cause impaired
      consciousness, syncope, atrioventricular block, and asystole due to vagal
      stimulation. Reports of acute coronary syndrome are very rare. Herein, we present
      the case of a 50-year-old husband and 42-year-old wife who, to improve sexual
      performance, intentionally ate honey from the Black Sea area of Turkey for 1
      week. Within 3 hours of consuming increased amounts of the honey, they presented
      at our emergency department with acute inferior myocardial infarctions. Coronary
      angiography revealed normal coronary arteries in both patients. Supportive
      treatment with atropine rapidly resolved the clinical symptoms and
      electrocardiographic irregularities. Grayanotoxin-containing rhododendron pollen
      was detected in the honey.In patients from geographic regions where mad honey can
      be obtained, mad-honey poisoning should be considered in the differential
      diagnosis of chest pain, particularly in the presence of unexplained
      bradyarrhythmia and hypotension. Sexual performance is a chief reason for the
      purchase of mad honey and self-treatment with it by persons of our patients'
      ages.

PMID- 22163141
TI  - Valvular heart disease with the use of fenfluramine-phentermine.
AB  - Exposure to the anorectic drug fenfluramine, alone or in combination with
      phentermine, a noradrenergic central nervous system stimulant, has been
      associated with unusual cardiac valvular morphology and resultant regurgitation
      of the left- and right-sided heart valves. The prevalence of significant valvular
      disease associated with the use of these anorectic drugs is reported to be as
      high as 23%. Herein, we report the occurrence of multivalvular disease and
      pulmonary hypertension associated with fenfluramine-phentermine use, discovered
      in an obese 59-year-old woman before expected gastric bypass surgery.

PMID- 22163142
TI  - Campylobacter fetus as cause of prosthetic valve endocarditis.
AB  - A 65-year-old woman who had previously undergone aortic root replacement with a
      bioprosthetic valve (Bentall operation) in treatment of annuloaortic ectasia
      became feverish after developing dental caries and was admitted to our hospital.
      Transesophageal echocardiography showed an 18 * 4-mm vegetation on her prosthetic
      valve. Campylobacter fetus was isolated on blood cultures, and she was diagnosed
      with infectious endocarditis. Aggressive combined antibiotic treatment was
      effective for her recovery. C. fetus infection is a rarely reported cause of
      prosthetic valve endocarditis.

PMID- 22163143
TI  - Unexpected embolization of Teflon pledget in the left main stem during: a Bentall
      operation.
AB  - We report the case of an 83-year-old man in whom acute left ventricular failure
      with ventricular arrhythmic storm developed during a Bentall operation. During re
      exploration of the annular and coronary ostial anastomoses, no abnormality was
      seen, and none of the common sequelae of aortic root replacement was evident. The
      application of retrograde cardioplegia yielded a Teflon pledget that had migrated
      into the distal part of the left main stem. The pledget was removed, the
      anastomoses were reestablished, and the patient recovered uneventfully. This case
      suggests that left ostial anastomosis re-exploration should be carefully
      considered when no other cause of coronary insufficiency is obvious, and that
      retrograde cardioplegia may be useful to detect embolization in the left coronary
      system.

PMID- 22163145
TI  - Serpentine coronary arteries: in a patient with apical hypertrophic
      cardiomyopathy.

PMID- 22163144
TI  - Myxoma at junction of inferior vena cava and right atrium: surgical excision.
AB  - Atrial myxomas are the most common primary cardiac tumors. In 20% of cases, they
      arise from the right atrium. Only a few such tumors are reported to have arisen
      from the inferior vena cava. We report a case in which we discovered, in a young,
      asymptomatic woman, an atrial myxoma arising from the anterior-superior junction
      of the inferior vena cava with the right atrium.Although transthoracic
      echocardiography is still considered the most important diagnostic imaging method
      for application to cardiac tumors, its use in our patient failed, probably due to
      the unusual location and small size of the mass. The diagnosis was made with the
      aid of transesophageal echocardiography, which proved its superiority and
      accuracy in this application.

PMID- 22163146
TI  - Spontaneous closure of post-myocardial infarction ventricular septal rupture.

PMID- 22163147
TI  - Isolated right ventricular myocardial infarction: mimicking anterior myocardial
      infarction in a patient with coronary artery bypass grafts.

PMID- 22163148
TI  - Contrast-induced coronary no-flow phenomenon: during diagnostic coronary
      angiography.

PMID- 22163149
TI  - Cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis:
      presenting as ventricular tachycardia.

PMID- 22163150
TI  - Percutaneous left atrial appendage closure: in a patient with hereditary
      hemorrhagic telangiectasia and atrial fibrillation.

PMID- 22163151
TI  - Pugmarks in the heart.

PMID- 22163152
TI  - Sweet syndrome, myocardial ischemia, and fatal rupture of an aneurysm of the
      posterior sinus of valsalva into the left ventricular cavity.

PMID- 22163154
TI  - A Realtime and Continuous Assessment of Cortisol in ISF Using Electrochemical
      Impedance Spectroscopy.
AB  - This study describes the functioning of a novel sensor to measure cortisol
      concentration in the interstitial fluid (ISF) of a human subject. ISF is
      extracted by means of vacuum pressure from micropores created on the stratum
      corneum layer of the skin. The pores are produced by focusing a near infrared
      laser on a layer of black dye material attached to the skin. The pores are viable
      for approximately three days after skin poration. Cortisol measurements are based
      on electrochemical impedance (EIS) technique. Gold microelectrode arrays
      functionalized with Dithiobis (succinimidyl propionate) self-assembled monolayer
      (SAM) have been used to fabricate an ultrasensitive, disposable, electrochemical
      cortisol immunosensor. The biosensor was successfully used for in-vitro
      measurement of cortisol in ISF. Tests in a laboratory setup show that the sensor
      exhibits a linear response to cortisol concentrations in the range 1 pm to 100
      nM. A small pilot clinical study showed that in-vitro immunosensor readings, when
      compared with commercial evaluation using enzyme-linked immunoassay (ELISA)
      method, correlated well with cortisol levels in saliva and ISF. Further,
      circadian rhythm could be established between the subject's ISF and the saliva
      samples collected over 24 hours time-period. Cortisol levels in ISF were found
      reliably higher than in saliva. This Research establishes the feasibility of
      using impedance based biosensor architecture for a disposable, wearable cortisol
      detector. The projected commercial in-vivo real-time cortisol sensor device,
      besides being minimally invasive, will allow continuous ISF harvesting and
      cortisol monitoring over 24 hours even when the subject is asleep. Forthcoming,
      this sensor could be interfaced to a wireless health monitoring system that could
      transfer sensor data over existing wide-area networks such as the internet and a
      cellular phone network to enable real-time remote monitoring of subjects.

PMID- 22163155
TI  - Efficacy and safety of ultra-low-dose Vagifem (10 mcg).
AB  - Vulvovaginal atrophy [VVA] is defined as inflammation of the vaginal epithelium
      due to atrophy secondary to decreased levels of circulating estrogen. There is
      currently only one approved method for the treatment of VVA, and that is the
      administration of exogenous estrogens. Overall, the ideal VVA treatment must have
      benefits, minimize risks, and enhance compliance in the patient while optimizing
      cost-effectiveness. Unfortunately, of the approximate 25% of symptomatic women
      that are thought to seek medical help, the proportion that receives hormone
      therapy may be small and its duration of use is short. Women have been very
      reluctant to take hormone therapy due to widely publicized results of the risks
      associated with hormone therapy. Thus, while menopausal hormone therapy was once
      accepted as the ideal approach for optimizing changes associated with menopause,
      prospective randomized clinical trials have challenged that view and have led to
      a marked decrease in the use of such therapy and increased search for low-dose
      therapies. This article will highlight the efficacy and safety of recently FDA
      approved Vagifem (10 mcg) in treatment of VVA.

PMID- 22163156
TI  - Noninvasive brain stimulation by radioelectric asymmetric conveyor in the
      treatment of agoraphobia: open-label, naturalistic study.
AB  - BACKGROUND: Agoraphobia is considered to be the most serious complication of
      panic disorder. It involves progressive development of debilitating anxiety
      symptoms related to being in situations where one would be extremely embarrassed
      and could not be rescued in the case of a panic attack. This study aimed to
      investigate the efficacy of noninvasive brain stimulation using a radioelectric
      asymmetric conveyor (REAC) for agoraphobia. PATIENTS AND METHODS: Twenty-three
      patients (3 males and 20 females) suffering from agoraphobia and without a
      history of panic disorder were evaluated by a psychiatrist using the Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and
      the Agoraphobia Scale (AS). The patients were subjected to two 18-session cycles
      of noninvasive brain stimulation with the REAC, according to an established
      therapeutic protocol called neuropsycho-physical optimization. RESULTS: Analyzing
      the anxiety and avoidance parameters of the AS after the first and second cycles
      of REAC treatment revealed variation in levels of response to treatment,
      including weak (AS item 7), moderate (AS items 10 and 13), and good responses (AS
      items 1-6, 8, 9, 11, 12, and 14-20). CONCLUSION: These results highlight the
      potential of the REAC to treat complex clinical situations such as agoraphobia,
      which is typically resistant to pharmacologic treatments. Furthermore, these data
      show the advantages of REAC treatment, even compared with modern cognitive
      behavioral therapy, including a relatively rapid and "stable" clinical response
      (just over 6 months) and economic cost.

PMID- 22163157
TI  - Social anxiety disorder: radio electric asymmetric conveyor brain stimulation
      versus sertraline.
AB  - PURPOSE: Social anxiety disorder (SAD) is a disabling condition that affects
      almost 5% of the general population. Many types of drugs have shown their
      efficacy in the treatment of SAD. There are also some data regarding
      psychotherapies, but no data are available today about the efficacy of brain
      stimulation techniques. The aim of the study is to compare the efficacy of
      noninvasive brain stimulation neuro psycho physical optimization (NPPO) protocol
      performed by radio electric asymmetric conveyor (REAC) with that of sertraline in
      adults with SAD. PATIENTS AND METHODS: Twenty SAD patients on sertraline were
      compared with 23 SAD patients who refused any drug treatment and who chose to be
      treated with NPPO-REAC brain stimulation. This was a 6-month, open-label,
      naturalistic study. Patients on sertraline received flexible doses, whereas NPPO
      REAC patients received two 18-session cycles of treatment. Clinical Global
      Improvement scale items "much improved" or "very much improved" and Liebowitz
      Social Anxiety Scale total score variation on fear and avoidance components were
      used to detect the results. The statistical analysis was performed with t-test.
      All measures <0.05 have been considered statistically significant. RESULTS: Ten
      of 23 subjects on NPPO-REAC and six of the 20 taking sertraline were much
      improved or very much improved 1 month after the first NPPO-REAC cycle (t1).
      Sixteen of the subjects on NPPO-REAC and ten of the subjects taking sertraline
      were much improved or very much improved 1 month after the second NPPO-REAC cycle
      (t2). In respect of the Liebowitz Social Anxiety Scale, at t1 NPPO-REAC resulted
      in statistically more efficacy for sertraline on both fear and avoidance total
      scores. At t2, NPPO-REAC resulted in statistically more efficacy for sertraline
      on fear but not on avoidance. CONCLUSION: NPPO-REAC is an effective treatment for
      SAD, allowing substantial and clinically meaningful reductions in symptoms and
      disability in comparison with sertraline.

PMID- 22163158
TI  - Evaluation of pharmacokinetics, user handling, and tolerability of peginterferon
      alfa-2a (40 kDa) delivered via a disposable autoinjector device.
AB  - BACKGROUND: Peginterferon alfa-2a (40 kDa) is currently administered using a
      prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new
      safety-engineered device designed to facilitate injection and reduce the risk of
      needlestick injuries. The analysis of two open-label Phase I trials evaluated the
      pharmacokinetics, successful administration, and tolerability of peginterferon
      alfa-2a when using the autoinjector. The studies were performed to support the
      filing and registration of the autoinjector device. METHODS: In trial 1, 50
      healthy adult subjects received one 180 MUg dose of peginterferon alfa-2a via the
      autoinjector. Serial blood samples were collected predose, up to 336 hours
      following drug administration, and at follow-up (28 +/- 3 days post-dosing) for
      noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients
      with chronic hepatitis C to 180 MUg peginterferon alfa-2a once weekly by the
      autoinjector or prefilled syringe for 3 weeks followed by the alternative device
      (prefilled syringe or autoinjector, respectively) for 3 weeks. Patients also
      received ribavirin. Administration by the devices was evaluated under direct
      observation by a study staff member and by patient subjective assessment.
      RESULTS: In trial 1, following a single dose of peginterferon alfa-2a, the
      maximum plasma concentration was 16.1 +/- 5.3 ng/mL (mean +/- standard
      deviation), and area under the concentration time curve (0-168 hours) was 1996 +/
      613 ng . hour/mL, similar to that reported using a vial/syringe or prefilled
      syringe. In trial 2, few patients showed handling difficulties with either
      device. Generally, patients were observed to be more satisfied and confident,
      followed instructions better, and successfully initiated injection with the
      autoinjector versus the prefilled syringe. Patients reported the autoinjector to
      be more convenient and easier to use. No pain or discomfort was experienced using
      the autoinjector. The autoinjector safety profile was consistent with that known
      for peginterferon alfa-2a/ribavirin. CONCLUSION: These results indicate that
      peginterferon alfa-2a can be successfully and safely delivered via the
      autoinjector and that the device is easy to handle.

PMID- 22163159
TI  - A rapid and highly sensitive protocol for the detection of Escherichia coli
      O157:H7 based on immunochromatography assay combined with the enrichment
      technique of immunomagnetic nanoparticles.
AB  - BACKGROUND: Escherichia coli O157:H7 (E. coli O157:H7) is an important pathogenic
      bacterium that threatens human health. A rapid, simple, highly sensitive, and
      specific method for the detection of E. coli O157:H7 is necessary. METHODS: In
      the present study, immunomagnetic nanoparticles (IMPs) were prepared with
      nanopure iron as the core, coated with E. coli O157:H7 polyclonal antibodies.
      These IMPs were used in combination with immunochromatographic assay (ICA) and
      used to establish highly sensitive and rapid kits (IMPs+ICA) to detect E. coli
      O157:H7. The kits were then used to detect E. coli O157:H7 in 150 food samples
      and were compared with conventional ICA to evaluate their efficacy. RESULTS: The
      average diameter of IMPs was 56 nm and the amount of adsorbed antibodies was
      106.0 MUg/mg. The sensitivity of ICA and IMPs+ICA was 10(5) colony-forming
      units/mL and 10(3) CFUs/mL, respectively, for purified E. coli O157:H7 solution.
      The sensitivity of IMPs+ICA was increased by two orders, and its specificity was
      similar to ICA. CONCLUSION: The kits have the potential to offer important social
      and economic benefits in the screening, monitoring, and control of food safety.

PMID- 22163160
TI  - Preparation of poly(ethylene glycol)/polylactide hybrid fibrous scaffolds for
      bone tissue engineering.
AB  - Polylactide (PLA) electrospun fibers have been reported as a scaffold for bone
      tissue engineering application, however, the great hydrophobicity limits its
      broad application. In this study, the hybrid amphiphilic poly(ethylene glycol)
      (PEG)/hydrophobic PLA fibrous scaffolds exhibited improved morphology with
      regular and continuous fibers compared to corresponding blank PLA fiber mats. The
      prepared PEG/PLA fibrous scaffolds favored mesenchymal stem cell (MSC) attachment
      and proliferation by providing an interconnected porous extracellular
      environment. Meanwhile, MSCs can penetrate into the fibrous scaffold through the
      interstitial pores and integrate well with the surrounding fibers, which is very
      important for favorable application in tissue engineering. More importantly, the
      electrospun hybrid PEG/PLA fibrous scaffolds can enhance MSCs to differentiate
      into bone-associated cells by comprehensively evaluating the representative
      markers of the osteogenic procedure with messenger ribonucleic acid quantitation
      and protein analysis. MSCs on the PEG/PLA fibrous scaffolds presented better
      differentiation potential with higher messenger ribonucleic acid expression of
      the earliest osteogenic marker Cbfa-1 and mid-stage osteogenic marker Col I. The
      significantly higher alkaline phosphatase activity of the PEG/PLA fibrous
      scaffolds indicated that these can enhance the differentiation of MSCs into
      osteoblast-like cells. Furthermore, the higher messenger ribonucleic acid level
      of the late osteogenic differentiation markers OCN (osteocalcin) and OPN
      (osteopontin), accompanied by the positive Alizarin red S staining, showed better
      maturation of osteogenic induction on the PEG/PLA fibrous scaffolds at the
      mineralization stage of differentiation. After transplantation into the thigh
      muscle pouches of rats, and evaluating the inflammatory cells surrounding the
      scaffolds and the physiological characteristics of the surrounding tissues, the
      PEG/PLA scaffolds presented good biocompatibility. Based on the good cellular
      response and excellent osteogenic potential in vitro, as well as the
      biocompatibility with the surrounding tissues in vivo, the electrospun PEG/PLA
      fibrous scaffolds could be one of the most promising candidates in bone tissue
      engineering.

PMID- 22163161
TI  - Preparation and biodistribution of 188Re-labeled folate conjugated human serum
      albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs) in vivo.
AB  - BACKGROUND: The purpose of this study was to develop intraperitoneal hyperthermic
      therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin
      chemotherapy, and magnetic particles of albumin. In addition, to combine the
      multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and
      radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide
      (188)Re-labeled folic acid ligand ((188)Re-folate-CDDP/HSA). METHODS: Human serum
      albumin was labeled with (188)Re using the pre-tin method. Reaction time and
      optimal conditions of labeling were investigated. The particles were
      intravenously injected into mice, which were sacrificed at different time points.
      Radioactivity per gram of tissue of percent injected dose (% ID/g) was measured
      in vital organs. The biodistribution of (188)Re-folate-CDDP/HAS magnetic
      nanoparticles was assessed. RESULTS: Optimal conditions for (188)Re-labeled
      folate-conjugated albumin combined with cisplatin magnetic nanoparticles were:
      0.1 mL of sodium gluconate solution (0.3 mol/L), 0.1 mL of concentrated
      hydrochloric acid with dissolved stannous chloride (10 mg/mL), 0.04 mL of acetic
      acid buffer solution (pH 5, 0.2 mol/L), 30 mg of folate-conjugated albumin
      combined with cisplatin magnetic nanoparticles, and (188)ReO(4) eluent (0.1 mL).
      The rate of (188)Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%,
      and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf
      serum at 37 degrees C. The major uptake tissues were the liver, kidney,
      intestine, and tumor after the (188)Re-folate-CDDP/HSA magnetic nanoparticles
      were injected into nude mice. Uptake of (188)Re-folate-CDDP/HSA magnetic
      nanoparticles increased gradually after injection, peaked at 8 hours with a value
      of 8.83 +/- 1.71, and slowly decreased over 24 hours in vivo. CONCLUSION: These
      results indicate that (188)Re-folate-CDDP/HSA magnetic nanoparticles can be used
      in radionuclide-targeted cancer therapy. Surface-modified albumin nanoparticles
      with folic acid ligand-labeled radionuclide ((188)Re) were successfully prepared,
      laying the foundation for a triple-killing effect of thermotherapy, chemotherapy,
      and radiation therapy.

PMID- 22163162
TI  - Comparative study of the in vitro and in vivo characteristics of cationic and
      neutral liposomes.
AB  - Neutral liposomes (NLP) exhibit preferential localization in solid tumors based
      on the enhanced permeation and retention (EPR) effect. Cationic liposomes (CLP)
      have a propensity for localizing in newly formed tumor vessels and they have a
      potentially enhanced antitumor effect. However, an increased amount of cationic
      lipids in liposomes also induces aggregation through electrostatic interactions
      between the liposomes and the anionic species in the circulation, which results
      in a reduced EPR effect. Consequently, it is important to investigate the
      characteristics of liposomes with different surface potentials in vitro to
      achieve an optimal intratumoral distribution and antitumor effect in vivo. In
      this study, the authors evaluated the characteristics of doxorubicin (DOX)-loaded
      NLPs, CLPs, polyethylene glycol (PEG)-modified NLPs (NLP-PEG), and PEGylated CLPs
      (CLP-PEG) (ie, encapsulation efficacy, zeta potential, size, membrane fluidity,
      aggregation in serum, and uptake of liposomes into rat aortic endothelial cells
      (RAECs)) to further understand their influences on the pharmacokinetics,
      biodistribution, and antitumor therapy in vivo. The results showed that increased
      amounts of cationic lipids resulted in severe liposome aggregation in the
      presence of serum, yet it did not alter the membrane fluidity to a large extent.
      The uptake of liposomes into RAECs, visualized by confocal fluorescence
      microscopy, confirmed the rapid uptake of CLP by the endothelial cells compared
      with NLP. However, the pharmacokinetics, biodistribution and anticancer
      efficacies of these liposomes in vivo revealed that the CLP with highly positive
      surface potentials exhibited reduced circulation times and poor distribution in
      tumors. The NLP-PEG exhibited the highest anticancer efficacy; CLP-PEG, the
      second highest; and CLP with the most positive surface potential, the lowest.
      These phenomena were mostly due to the rapid aggregation in serum and subsequent
      accumulation in the lungs upon the intravenous injection of the CLP. Caution
      should be exercised when chemotherapeutic drugs are loaded into CLP for tumor
      therapy.

PMID- 22163163
TI  - Preparation of hippurate-zinc layered hydroxide nanohybrid and its synergistic
      effect with tamoxifen on HepG2 cell lines.
AB  - BACKGROUND: A new simple preparation method for a hippurate-intercalated zinc
      layered hydroxide (ZLH) nanohybrid has been established, which does not need an
      anion-exchange procedure to intercalate the hippurate anion into ZLH interlayers.
      METHODS: The hippuric acid nanohybrid (HAN) was prepared by direct reaction of an
      aqueous suspension of zinc oxide with a solution of hippuric acid via a one-step
      method. RESULTS: The basal spacing of the nanohybrid was 21.3 A, indicating that
      the hippurate anion was successfully intercalated into the interlayer space of
      ZLH, and arranged in a monolayer fashion with the carboxylate group pointing
      toward the ZLH inorganic interlayers. A Fourier transform infrared study
      confirmed the formation of the nanohybrid, while thermogravimetry and
      differential thermogravimetry analyses showed that the thermal stability of the
      nanohybrid was markedly enhanced. The loading of hippurate in the nanohybrid was
      estimated to be about 38.7% (w/w), and the release of hippurate from the
      nanohybrid was of a controlled manner, and therefore the resulting material was
      suitable for use as a controlled-release formulation. HAN has synergistic
      properties with tamoxifen toward a HepG2 cell line, with an IC50 value of 0.35
      compared with hippurate. In the antiproliferative assay, the ratio of viable
      cells account for cells treated by the combination tamoxifen with HAN to
      untreated cells was sharply reduced from 66% to 13% after 24 and 72 hours,
      respectively. CONCLUSION: The release of hippuric acid anions from HAN occurred
      in a controlled manner, and the resulting material is suitable for a controlled
      release formulation.

PMID- 22163164
TI  - The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in
      treating resistant leukemia in animals.
AB  - BACKGROUND: Multidrug resistance (MDR) of cancers can be circumvented by inducing
      programmed cell death, which is known as apoptosis. Mitochondria play a crucial
      role in apoptosis. Mitochondria-specific therapy would provide an efficient
      strategy for treating resistant cancers. DESIGN AND METHODS: A strategy was
      proposed here to overcome MDR by designing cancer mitochondria-specific drug
      loaded liposomes, namely, antiresistant epirubicin mitosomes, aimed at treating
      resistant leukemia by targeting mitochondria. Evaluations were performed on human
      chronic leukemia K562, MDR K562/ADR cells, and female BALB/c nude mice
      xenografted with MDR K562/ADR cells. The liposomes were characterized through
      assays of cytotoxicity, mitochondrial targeting, caspase-9 and caspase-3,
      antitumor activities, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick
      end labeling) analysis. RESULTS: The average size of antiresistant epirubicin
      mitosomes was in the range of 105-115 nm. Antiresistant epirubicin mitosomes were
      effective in inhibiting proliferation of MDR K562/ADR cells in vitro and
      selectively accumulated into the mitochondria. Caspase-9 and caspase-3 activity
      was increased after applying antiresistant epirubicin mitosomes. In xenografted
      resistant MDR K562/ADR tumor in nude mice, antiresistant tumor effect of
      antiresistant epirubicin mitosomes was evidently observed. Apoptotic inducing
      effects by antiresistant epirubicin mitosomes were noticeably evidenced via
      mitochondrial pathway. CONCLUSIONS: Antiresistant epirubicin mitosomes had
      significant inhibitory effect against resistant leukemia in vitro and in vivo,
      hence providing a promising strategy for improving therapeutic efficacy in
      resistant human leukemia.

PMID- 22163165
TI  - Surgical wound healing using hemostatic gauze scaffold loaded with nanoparticles
      containing sustained-release granulocyte colony-stimulating factor.
AB  - BACKGROUND: The therapeutic strategies for malignant melanoma are still cancer
      chemotherapy, radiotherapy, and tumor resection. However, these therapeutic
      strategies often lead to a reduced neutrophilic granulocyte count or loss of more
      blood after surgical tumor resection. In this study, we developed a formulation
      of hemostatic gauze impregnated with sustained-release granulocyte colony
      stimulating factor (G-CSF) with increasing of the neutrophilic granulocyte count
      in the blood following chemotherapy and decreasing blood loss after surgical
      tumor resection. METHODS: We designed a formulation with both hemostatic
      properties and increased neutrophil content to be used in cancer chemotherapy,
      radiotherapy, and tumor resection, comprising a hemostatic gauze as a scaffold
      and (G-CSF)-loaded dextran nanoparticles coated with polylactic-co- glycolic acid
      (PLGA) solution fabricated by direct spray-painting onto the scaffold and then
      vacuum-dried at room temperature. The performance of this system was evaluated in
      vitro and in vivo. RESULTS: Nearly zero-order release of G-CSF was recorded for
      12-14 days, and the cumulative release of G-CSF retained over 90% of its
      bioactivity in a NFS-60 cell line proliferation assay when the scaffold was
      incubated in phosphate-buffered saline (pH 7.4) at 37 degrees C. The in vivo
      hemostatic efficacy of this formulation was greater than that of native G-CSF,
      the scaffold directly spray-painted with G-CSF solution or PLGA organic solution
      as a coating, or when a blank scaffold was covered with the coating. CONCLUSION:
      Our results suggest that this formulation has both hemostatic properties and
      increased neutrophil activity.

PMID- 22163166
TI  - Novel mucus-penetrating liposomes as a potential oral drug delivery system:
      preparation, in vitro characterization, and enhanced cellular uptake.
AB  - BACKGROUND: The aim of this study was to investigate the intestinal mucus
      penetrating properties and intestinal cellular uptake of two types of liposomes
      modified by Pluronic F127 (PF127). METHODS: The two types of liposomes, ie, PF127
      inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film
      hydration method followed by extrusion, in which coumarin 6 was loaded as a
      fluorescence marker. A modified Franz diffusion cell mounted with the intestinal
      mucus of rats was used to study the diffusion characteristics of the two types of
      PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed
      using confocal laser scanning microcopy as well as flow cytometry. RESULTS: The
      diffusion efficiency of the two types of PF127-modified liposomes through
      intestinal rat mucus was 5-7-fold higher than that of unmodified liposomes.
      Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly
      higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower
      cellular uptake. Moreover, and interestingly, the two types of PF127-modified
      liposomes showed different cellular uptake mechanisms in Caco-2 cells.
      CONCLUSION: PF127-inlaid liposomes with improved intestinal mucus-penetrating
      ability and enhanced cellular uptake might be a potential carrier candidate for
      oral drug delivery.

PMID- 22163167
TI  - Cost-effectiveness analysis of initial HIV treatment under Italian guidelines.
AB  - INTRODUCTION: Since the mid-1990s, highly active antiretroviral therapy (HAART)
      has modified the clinical course of human immunodeficiency virus (HIV) infection,
      reducing the rate of disease progression, the incidence of opportunistic
      infections, and mortality. The authors of this paper performed an economic
      analysis to estimate the cost-effectiveness of the HAART regimens in Italy for
      managing HIV-infected patients according to national guidelines. PATIENTS AND
      METHODS: The incremental cost-effectiveness analysis was carried out by means of
      a Markov model, which through a decision-analytic approach, made it possible to
      compare the studied antiretroviral regimens. The population considered in the
      model consisted of adult subjects with HIV who received antiretroviral HAART
      treatment for the first time. The population considered in the analysis reflects
      the patients' characteristics according to one of the regional surveillance
      systems HIV/AIDS infection report currently operating in Italy. The analysis was
      carried out from the point of view of the Italian health care system. The
      considered outcome measures were quality-adjusted life years (QALYs) and direct
      health costs calculated for the year 2010. Both the outcomes (QALYs) and the
      costs were discounted by 3.5%. The time horizon adopted in the model was 10
      years. RESULTS: The model shows, in terms of cost per gained QALY, single tablet
      regimen (STR) appeared to be the most cost-effective therapeutic choice
      (?22,017), followed by tenofovir (TDF) + lamivudine + efavirenz (EFV) (?24,526),
      and TDF/emtricitabine (FTC) + nevirapine (?26,416), and TDF + FTC + EFV
      (?26,558); the remaining strategies have an incremental cost-effectiveness ratio
      (ICER) value varying from ?28,000 to ?41,000 per QALY. The sensitivity analysis
      on the main variables confirmed the validity of the base case scenario.
      CONCLUSION: STR is the most cost-effective treatment strategy, compared with the
      other therapeutic regimens recommended by the Italian guidelines. All the ICER
      values of the various regimens considered by the Italian guidelines were lower
      than the threshold value of ?50,000 commonly accepted at the international level.
      The model developed represents a tool for policy makers and health care
      professionals to make short- and long-term cost projections and thus evaluate
      their impact on the available budgets for HIV patients.

PMID- 22163168
TI  - Cost-utility analysis of immune tolerance induction therapy versus on-demand
      treatment with recombinant factor VII for hemophilia A with high titer inhibitors
      in Iran.
AB  - BACKGROUND: In developing countries, the treatment of hemophilia patients with
      inhibitors is presently the most challenging and serious issue in hemophilia
      management, direct costs of clotting factor concentrates accounting for >98% of
      the highest economic burden absorbed for the health care of patients in this
      setting. In the setting of chronic diseases, cost-utility analysis, which takes
      into account the beneficial effects of a given treatment/health care intervention
      in terms of health-related quality of life, is likely to be the most appropriate
      approach. OBJECTIVE: The aim of this study was to assess the incremental cost
      effectiveness ratios of immune tolerance induction (ITI) therapy with plasma
      derived factor VIII concentrates versus on-demand treatment with recombinant
      activated FVIIa (rFVIIa) in hemophilia A with high titer inhibitors from an
      Iranian Ministry of Health perspective. METHODS: This study was based on the
      study of Knight et al, which evaluated the cost- effectiveness ratios of
      different treatments for hemophilia A with high-responding inhibitors. To adapt
      Knight et al's results to the Iranian context, a few clinical parameters were
      varied, and cost data were replaced with the corresponding Iranian estimates of
      resource use. The time horizon of the analysis was 10 years. One-way sensitivity
      analyses were performed, varying the cost of the clotting factor, the drug dose,
      and the administration frequency, to test the robustness of the analysis.
      RESULTS: Comparison of the incremental cost-effectiveness ratios between the
      three ITI protocols and the on-demand regimen with rFVIIa shows that all three
      ITI protocols dominate the on-demand regimen with rFVIIa. Between the ITI
      protocols the low-dose ITI protocol dominates both the Bonn ITI protocol and the
      Malmo ITI protocol and would be the preferred ITI protocol. All of the three ITI
      protocols dominate the on-demand strategy, as they have both a lower average
      lifetime cost and higher quality-adjusted life-years (QALYs) gained. The cost per
      QALY gained for the Bonn ITI protocol compared with the Malmo ITI protocol was
      $249,391.84. The cost per QALY gained for the Bonn ITI protocol compared with the
      low-dose ITI protocol was $842,307.69. CONCLUSION: The results of data derived
      from our study suggest that the low-dose ITI protocol may be a less expensive
      and/or more cost-effective option compared with on-demand first-line treatment
      with rFVIIa.

PMID- 22163169
TI  - Bilateral cuffed tunnelled femoral dialysis catheters.

PMID- 22163170
TI  - Kidney function and mortality post-liver transplant in the Model for End-Stage
      Liver Disease era.
AB  - The Model for End-Stage Liver Disease (MELD) score incorporates serum creatinine
      and was introduced to facilitate allocation of orthotopic liver transplantation
      (LT). The objective is to determine the impact of MELD and kidney function on all
      cause mortality. Among LTs performed in a tertiary referral hospital between 1995
      and 2009, 419 cases were studied. Cox proportional hazards models were
      constructed to estimate the hazard ratios (HR) and 95% confidence intervals (CI)
      for death. Over mean follow-ups of 8.4 and 3.1 years during the pre-MELD and MELD
      era, 57 and 63 deaths were observed, respectively. Those transplanted during the
      MELD era had a higher likelihood of hepatorenal syndrome (8% vs 2%, P < 0.01),
      lower kidney function (median estimated glomerular filtration rate [eGFR] 77.8 vs
      92.6 mL/ min/1.73 m(2), P < 0.01), and more pretransplantation renal replacement
      therapy (RRT) (5% vs 1%; P < 0.01). All-cause mortality risk was similar in the
      MELD vs the pre-MELD era (HR: 0.98, 95% CI: 0.58-1.65). The risk of death,
      however, was nearly 3-fold greater (95% CI: 1.14-6.60) among those requiring pre-
      transplant RRT. Similarly, eGFR < 60 mL/min/1.73 m(2) post-transplant was
      associated with a 2.5-fold higher mortality (95% CI: 1.48-4.11). The study
      suggests that MELD implementation had no impact on all-cause mortality post-LT.
      However, the need for pre-transplant RRT and post-transplant kidney dysfunction
      was associated with a more than 2-fold greater risk of subsequent death.

PMID- 22163171
TI  - Evaluation of biochemical urinary stone composition and its relationship to tap
      water hardness in Qom province, central Iran.
AB  - PURPOSE: The aim of this study was to evaluate the biochemical stone composition
      in general population of Qom province, central Iran, and its relationship with
      high tap water hardness. MATERIALS AND METHODS: In a prospective study, from
      March 2008 to July 2011, biochemical analysis of urinary stones in patients
      living in Qom province for at least 5 years was performed. Stones were retrieved
      by spontaneous passage, endoscopic or open surgery, and after extracorporeal
      shockwave lithotripsy. Demographic findings and the drinking water supply of
      patients were evaluated and compared with biochemical stone analysis. RESULTS:
      Stone analysis was performed in 255 patients. The most dominant composition of
      urinary stones was calcium oxalate (73%), followed by uric acid (24%), ammonium
      urate (2%), and cystine (1%). The peak incidence of urinary stone was in patients
      in their forties. Overall male to female ratio was 4.93:1. CONCLUSION: The
      dominant stone composition in inhabitants of central Iran, where tap water
      hardness is high, was calcium oxalate stones. On the basis of this study,
      biochemical urinary stone composition of Qom does not differ from other regions
      of Iran with lower water hardness.

PMID- 22163172
TI  - Fat-free weight prediction in morbidly obese females.
AB  - PURPOSE: Precise estimation of creatinine clearance in obese individuals relies
      on the appropriate assessment of lean body weight (LBW). Anthropometric methods
      of predicting LBW have not been validated in morbidly obese populations. PATIENTS
      AND METHODS: Using an existing dataset of anthropometric data for a female cohort
      with morbid obesity who had undergone measured FFW with dual energy
      absorptiometry, we evaluated the performance of five previously reported
      estimating equations for the prediction of LBW. Linear regression was used to
      derive a new LBW prediction formula and was then compared with the other
      formulae. RESULTS: Seventy females (mean [standard deviation] age, weight, and
      body mass index 43.0 [11.0] years, 128.1 [13.8] kg, and 48.3 [4.8] kg/m(2),
      respectively) were identified. LBW as estimated by the method of Garrow and
      Webster correlated well (r = 0.87) with measured mass while demonstrating the
      highest accuracy, best precision, and smallest bias (93%, 2.1 kg, and 2.9 kg,
      respectively; P < 0.0001 for all comparisons). The derived formula further
      improved bias, precision, and accuracy. CONCLUSION: Among females with morbid
      obesity, most previously reported estimating equations for LBW predicted FFW
      poorly. These findings have important clinical implications for the assessment of
      kidney function and for safe and effective drug dosing.

PMID- 22163173
TI  - HIV voluntary counseling and testing practices among military personnel and
      civilian residents in a military cantonment in southeastern Nigeria.
AB  - BACKGROUND: Voluntary counseling and testing (VCT) services are expected to lower
      rates of HIV transmission through a reduction in high-risk sexual behavior and
      through improved access to medical treatment, care, and support. However,
      increasing access to and uptake of VCT, especially among groups at high risk for
      HIV infection, has remained a major challenge in Africa. PURPOSE: The study was
      undertaken to determine the uptake of VCT (measured by whether study participants
      had ever received an HIV test) and the factors influencing this practice among
      military and civilian residents of a military cantonment in Abakaliki,
      southeastern Nigeria. METHODS: A cross-sectional descriptive survey of all
      cantonment residents aged between 20 and 64 years was conducted. A multistage
      sampling technique was used to establish the sample size; data were collected
      from 350 military and civilian cantonment residents using a pretested
      questionnaire. Data were analyzed using SPSS software (v 16.0; SPSS Inc, Chicago,
      IL) and the significance of any association was tested at P < 0.05 using the chi
      square statistic. RESULTS: One hundred and forty-five (41.4%) respondents
      reported having ever been tested for HIV; however, only 44 (12.6%) respondents
      had received the test between 4 and 12 months prior to the survey period. Some of
      the significant factors that positively influenced uptake of VCT were awareness
      of VCT (P < 0.001), education level (P < 0.006), and knowledge of antiretroviral
      therapy benefits (P < 0.01). CONCLUSION: The uptake of VCT by the residents of
      the cantonment was low. The establishment of VCT services in the cantonment is
      urgently recommended, together with the targeting of high-risk population groups
      in HIV/AIDS and VCT information dissemination efforts.

PMID- 22163174
TI  - Every Patient is a Cardiopulmonary Patient.

PMID- 22163175
TI  - A Preliminary Exploration of the Effects of a 6-week Interactive Video Dance
      Exercise Program in an Adult Population.
AB  - PURPOSE: The purpose of this study was to determine the effects of a 6-week
      interactive video dance game (IVDG) program on adult participants'
      cardiorespiratory status and body mass index (BMI). METHODS: Twenty-seven healthy
      adult participants attended IVDG sessions over a 6-week period. Participants
      completed pre- and post-testing consisting of a submaximal VO(2) treadmill test,
      assessment of resting heart rate (RHR) and blood pressure (BP), BMI, and general
      health questionnaires. Data were analyzed using descriptives, paired t-tests to
      assess pre-to post-testing differences, and one-way ANOVAs to analyze variables
      among select groups of participants. Questionnaire data was manually coded and
      assessed. RESULTS: Twenty participants attended at least 75% of available
      sessions and were used in data analysis. Mean BMI decreased significantly (from
      26.96 kg/m(2) to 26.21 kg/m(2); 2.87%) and cardiorespiratory fitness measured by
      peak VO(2) increased significantly (from 20.63 ml/kg/min to 21.69 ml/kg/min;
      5.14%). Most participants reported that the IVDG program was a good workout, and
      that they were encouraged to continue or start an exercise routine. Forty percent
      reported improvements in sleep, and nearly half stated they had or were
      considering purchasing a home version of a video dance game. CONCLUSIONS:
      Interactive video dance game is an effective and enjoyable exercise program for
      adults who wish to decrease their BMI and improve components of cardiorespiratory
      fitness.

PMID- 22163176
TI  - A 12-week Interdisciplinary Intervention Program for Children who are Obese.
AB  - Childhood obesity is a growing problem, for which multi-disciplinary
      interventions are needed. PURPOSE: This interdisciplinary intervention program
      was designed to improve the health of children who were obese. METHODS: Twenty
      five children, mean age 8.1 (1.5) years; body mass index (BMI)> 98(th)
      percentile, and their parents completed the 12-week (3 days/wk) intervention
      consisting of aerobic and resistance exercise appropriate to age and
      developmental levels. Baseline and posttest measures of blood values, fitness,
      and cardiovascular risk factors were performed. Data were analyzed using paired t
      tests with significance accepted at P <= .05. RESULTS: Significant differences
      between means (SD) for pre- and post-measurements were, respectively: BMI 30.31
      (4.56), 27.80 (4.54), body-fat percent 43.7 (11.5), 40.7 (10.9), waist
      circumference 82.1 (7.1), 80.4(6.1) cm, calf circumference 34.2 (3.1), 35.2 (3.1)
      cm; step-test heart rate 137 (20), 126 (12) bpm, push-ups 1.0 (1.8), 5.6 (3.8),
      sit-ups 23.6 (12.7), 33.2 (13.8), sit-and-reach 35.1 (7.4), 41.2 (5.8) cm;
      systolic BP 102 (10), 108 (9) mmHg, glucose 4.9(0.3), 4.8 (0.4) mmol/L, total
      cholesterol 4.6 (1.0), 4.2 (0.8) mmol/L, ALT 41 (9), 35 (8) U/L, bilirubin 6.3
      (2.4), 5.6 (2.1) MUmol/L, and BUN 4.9 (1.1), 4.3 (0.9) mmol/L. CONCLUSIONS: This
      interdisciplinary intervention program positively affected the fitness and health
      status of children who were obese by involving the children and parents.

PMID- 22163177
TI  - A whole-body model for glycogen regulation reveals a critical role for substrate
      cycling in maintaining blood glucose homeostasis.
AB  - Timely, and sometimes rapid, metabolic adaptation to changes in food supply is
      critical for survival as an organism moves from the fasted to the fed state, and
      vice versa. These transitions necessitate major metabolic changes to maintain
      energy homeostasis as the source of blood glucose moves away from ingested
      carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The
      integration of hepatic glycogen regulation with extra-hepatic energetics is a key
      aspect of these adaptive mechanisms. Here we use computational modeling to
      explore hepatic glycogen regulation under fed and fasting conditions in the
      context of a whole-body model. The model was validated against previous
      experimental results concerning glycogen phosphorylase a (active) and glycogen
      synthase a dynamics. The model qualitatively reproduced physiological changes
      that occur during transition from the fed to the fasted state. Analysis of the
      model reveals a critical role for the inhibition of glycogen synthase phosphatase
      by glycogen phosphorylase a. This negative regulation leads to high levels of
      glycogen synthase activity during fasting conditions, which in turn increases
      substrate (futile) cycling, priming the system for a rapid response once an
      external source of glucose is restored. This work demonstrates that a mechanistic
      understanding of the design principles used by metabolic control circuits to
      maintain homeostasis can benefit from the incorporation of mathematical
      descriptions of these networks into "whole-body" contextual models that mimic in
      vivo conditions.

PMID- 22163179
TI  - An acute case of intoxication with cyanobacteria and cyanotoxins in recreational
      water in Salto Grande Dam, Argentina.
AB  - Cyanobacterial blooms and hepatotoxic microcystins (MCs) usually occur in summer,
      constituting a sanitary and environmental problem in Salto Grande Dam, Argentina.
      Water sports and recreational activities take place in summer in this lake. We
      reported an acute case of cyanobacterial poisoning in Salto Grande dam,
      Argentina, which occurred in January 2007. Accidentally, a young man was immersed
      in an intense bloom of Microcystis spp. A level of 48.6 MUg.L(-1) of microcystin
      LR was detected in water samples. Four hours after exposure, the patient showed
      nausea, abdominal pain and fever. Three days later, dyspnea and respiratory
      distress were reported. The patient was hospitalized in intensive care and
      diagnosed with an atypical pneumonia. Finally, a week after the exposure, the
      patient developed a hepatotoxicosis with a significant increase of hepatic damage
      biomarkers (ALT, AST and gammaGT). Complete recovery took place within 20 days.
      This is the first study to show an acute intoxication with microcystin-producing
      cyanobacteria blooms in recreational water.

PMID- 22163178
TI  - Protease-resistant prions selectively decrease Shadoo protein.
AB  - The central event in prion diseases is the conformational conversion of the
      cellular prion protein (PrP(C)) into PrP(Sc), a partially protease-resistant and
      infectious conformer. However, the mechanism by which PrP(Sc) causes neuronal
      dysfunction remains poorly understood. Levels of Shadoo (Sho), a protein that
      resembles the flexibly disordered N-terminal domain of PrP(C), were found to be
      reduced in the brains of mice infected with the RML strain of prions [1],
      implying that Sho levels may reflect the presence of PrP(Sc) in the brain. To
      test this hypothesis, we examined levels of Sho during prion infection using a
      variety of experimental systems. Sho protein levels were decreased in the brains
      of mice, hamsters, voles, and sheep infected with different natural and
      experimental prion strains. Furthermore, Sho levels were decreased in the brains
      of prion-infected, transgenic mice overexpressing Sho and in infected
      neuroblastoma cells. Time-course experiments revealed that Sho levels were
      inversely proportional to levels of protease-resistant PrP(Sc). Membrane
      anchoring and the N-terminal domain of PrP both influenced the inverse
      relationship between Sho and PrP(Sc). Although increased Sho levels had no
      discernible effect on prion replication in mice, we conclude that Sho is the
      first non-PrP marker specific for prion disease. Additional studies using this
      paradigm may provide insight into the cellular pathways and systems subverted by
      PrP(Sc) during prion disease.

PMID- 22163180
TI  - Pectenotoxin-2 from marine sponges: a potential anti-cancer agent-a review.
AB  - Pectenotoxin-2 (PTX-2), which was first identified as a cytotoxic entity in
      marine sponges, has been reported to display significant cytotoxicity to human
      cancer cells where it inhibits mitotic separation and cytokinesis through the
      depolymerization of actin filaments. In the late stage of endoreduplication, the
      effects of PTX-2 on different cancer cells involves: (i) down-regulation of anti
      apoptotic Bcl-2 members and IAP family proteins; (ii) up-regulation of pro
      apoptotic Bax protein and tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL)-receptor 1/receptor 2 (DR4/DR5); and (iii) mitochondrial dysfunction. In
      addition, PTX-2 induces apoptotic effects through suppression of the nuclear
      factor kappaB (NF-kappaB) signaling pathway in several cancer cells. Analysis of
      cell cycle regulatory proteins showed that PTX-2 increases phosphorylation of
      Cdc25c and decreases protein levels of Cdc2 and cyclin B1. Cyclin-dependent
      kinase (Cdk) inhibitor p21 and Cdk2, which are associated with the induction of
      endoreduplication, were upregulated. Furthermore, it was found that PTX-2
      suppressed telomerase activity through the transcriptional and post-translational
      suppression of hTERT. The purpose of this review was to provide an update
      regarding the anti-cancer mechanism of PTX-2, with a special focus on its effects
      on different cellular signaling cascades.

PMID- 22163181
TI  - Sulfated-polysaccharide fraction from red algae Gracilaria caudata protects mice
      gut against ethanol-induced damage.
AB  - The aim of the present study was to investigate the gastroprotective activity of
      a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae
      Gracilaria caudata and the mechanism underlying the gastroprotective activity.
      Male Swiss mice were treated with PLS (3, 10, 30 and 90 mg.kg(-1), p.o.), and
      after 30 min, they were administered 50% ethanol (0.5 mL/25 g(-1), p.o.). One
      hour later, gastric damage was measured using a planimeter. Samples of the
      stomach tissue were also obtained for histopathological assessment and for assays
      of glutathione (GSH) and malondialdehyde (MDA). Other groups were pretreated with
      l-NAME (10 mg.kg(-1), i.p.), dl-propargylglycine (PAG, 50 mg.kg(-1), p.o.) or
      glibenclamide (5 mg.kg(-1), i.p.). After 1 h, PLS (30 mg.kg(-1), p.o.) was
      administered. After 30 min, ethanol 50% was administered (0.5 mL/25 g(-1), p.o.),
      followed by sacrifice after 60 min. PLS prevented-ethanol-induced macroscopic and
      microscopic gastric injury in a dose-dependent manner. However, treatment with l
      NAME or glibenclamide reversed this gastroprotective effect. Administration of
      propargylglycine did not influence the effect of PLS. Our results suggest that
      PLS has a protective effect against ethanol-induced gastric damage in mice via
      activation of the NO/K(ATP) pathway.

PMID- 22163182
TI  - Examination of marine-based cultivation of three demosponges for acquiring
      bioactive marine natural products.
AB  - Marine sponges are an extremely rich and important source of natural products.
      Mariculture is one solution to the so-called "supply problem" that often hampers
      further studies and development of novel compounds from sponges. We report the
      extended culture (767 days) at sea in depths of 10 and 20 m of three sponge
      species: Negombata magnifica, Amphimedon chloros and Theonella swinhoei that
      produce latrunculin-B, halitoxin and swinholide-A, respectively. Since sponge
      associated microorganisms may be the true producers of many of the natural
      products found in sponges and also be linked to the health of the sponges, we
      examined the stability of the bacterial communities in cultured versus wild
      sponges. Growth rate of the sponges (ranging from 308 to 61 and -19 (%)(year(-1))
      in N. magnifica, A. chloros and T. swinhoei, respectively) differed significantly
      between species but not between the two depths at which the species were
      cultivated. Survivorship varied from 96% to 57%. During culture all species
      maintained the content of the desired natural product. Denaturing gradient gel
      electrophoresis analysis of the sponge-associated bacterial consortia revealed
      that differences existed between cultured and wild sponges in T. swinhoei and A.
      chloros but the communities remained quite stable in N. magnifica. The
      cultivation technique for production of natural products was found to be most
      appropriate for N. magnifica, while for T. swinhoei and A. chloros it was less
      successful, because of poorer growth and survival rates and shifts in their
      bacterial consortia.

PMID- 22163183
TI  - New polyether triterpenoids from Laurencia viridis and their biological
      evaluation.
AB  - The red seaweed Laurencia viridis is a rich source of secondary metabolites
      derived from squalene. New polyethers, such as iubol (2), 22-hydroxy-15(28)-
      dehydrovenustatriol (3), 1,2-dehydropseudodehydrothyrsiferol (4), and
      secodehydrothyrsiferol (5) have been isolated and characterized from this alga.
      The structures were determined through the interpretation of NMR spectroscopic
      data and the relative configuration was proposed on the basis of NOESY spectrum
      and biogenetic considerations. All new compounds exhibited significant cytotoxic
      activity against a panel of cancer cell lines.

PMID- 22163184
TI  - Bacteriophages with potential for inactivation of fish pathogenic bacteria:
      survival, host specificity and effect on bacterial community structure.
AB  - Phage therapy may represent a viable alternative to antibiotics to inactivate
      fish pathogenic bacteria. Its use, however, requires the awareness of novel
      kinetics phenomena not applied to conventional drug treatments. The main
      objective of this work was to isolate bacteriophages with potential to inactivate
      fish pathogenic bacteria, without major effects on the structure of natural
      bacterial communities of aquaculture waters. The survival was determined in
      marine water, through quantification by the soft agar overlay technique. The host
      specificity was evaluated by cross infection. The ecological impact of phage
      addition on the structure of the bacterial community was evaluated by DGGE of PCR
      amplified 16S rRNA gene fragments. The survival period varied between 12 and 91
      days, with a higher viability for Aeromonas salmonicida phages. The phages of
      Vibrio parahaemolyticus and of A. salmonicida infected bacteria of different
      families with a high efficacy of plating. The specific phages of pathogenic
      bacteria had no detectable impact on the structure of the bacterial community. In
      conclusion, V. parahaemolyticus and A. salmonicida phages show good survival time
      in marine water, have only a moderated impact on the overall bacterial community
      structure and the desired specificity for host pathogenic bacteria, being
      potential candidates for therapy of fish infectious diseases in marine
      aquaculture systems.

PMID- 22163185
TI  - Tasco((r)), a product of Ascophyllum nodosum, imparts thermal stress tolerance in
      Caenorhabditis elegans.
AB  - Tasco((r)), a commercial product manufactured from the brown alga Ascophyllum
      nodosum, has been shown to impart thermal stress tolerance in animals. We
      investigated the physiological, biochemical and molecular bases of this induced
      thermal stress tolerance using the invertebrate animal model, Caenorhabiditis
      elegans. Tasco((r)) water extract (TWE) at 300 MUg/mL significantly enhanced
      thermal stress tolerance as well as extended the life span of C. elegans. The
      mean survival rate of the model animals under thermal stress (35  degrees C)
      treated with 300 MUg/mL and 600 MUg/mL TWE, respectively, was 68% and 71% higher
      than the control animals. However, the TWE treatments did not affect the nematode
      body length, fertility or the cellular localization of daf-16. On the contrary,
      TWE under thermal stress significantly increased the pharyngeal pumping rate in
      treated animals compared to the control. Treatment with TWE also showed
      differential protein expression profiles over control following 2D gel
      electrophoresis analysis. Furthermore, TWE significantly altered the expression
      of at least 40 proteins under thermal stress; among these proteins 34 were up
      regulated while six were down-regulated. Mass spectroscopy analysis of the
      proteins altered by TWE treatment revealed that these proteins were related to
      heat stress tolerance, energy metabolism and a muscle structure related protein.
      Among them heat shock proteins, superoxide dismutase, glutathione peroxidase,
      aldehyde dehydrogenase, saposin-like proteins 20, myosin regulatory light chain
      1, cytochrome c oxidase RAS-like, GTP-binding protein RHO A, OS were
      significantly up-regulated, while eukaryotic translation initiation factor 5A-1
      OS, 60S ribosomal protein L18 OS, peroxiredoxin protein 2 were down regulated by
      TWE treatment. These results were further validated by gene expression and
      reporter gene expression analyses. Overall results indicate that the water
      soluble components of Tasco((r)) imparted thermal stress tolerance in the C.
      elegans by altering stress related biochemical pathways.

PMID- 22163186
TI  - Gustatory detection of tetrodotoxin and saxitoxin, and its competitive inhibition
      by quinine and strychnine in freshwater fishes.
AB  - Fish detect extremely low levels of marine toxins tetrodotoxin (TTX) and
      saxitoxin (STX) via the specialized gustatory receptor(s). Physiological and
      pharmacological studies show that receptor(s) for TTX and STX are distinct from
      those which detect feeding stimulant amino acids and bile acids, and that TTX and
      STX do not share the same receptor populations, while interacting with quinine
      and strychnine in a competitive fashion suggestive of an antidotal relationship.

PMID- 22163187
TI  - Analytical challenges: determination of tetrodotoxin in human urine and plasma by
      LC-MS/MS.
AB  - Tetrodotoxin (TTX) is a powerful sodium channel blocker found in puffer fish and
      some marine animals. Cases of TTX poisoning most often result from puffer fish
      ingestion. Diagnosis is mainly from patient's signs and symptoms or the detection
      of TTX in the leftover food. If leftover food is unavailable, the determination
      of TTX in the patient's urine and/or plasma is essential to confirm the
      diagnosis. Although various methods for the determination of TTX have been
      published, most of them are for food tissue samples. Dealing with human urine and
      blood samples is much more challenging. Unlike in food, the amount of toxin in
      the urine and blood of a patient is generally extremely low; therefore a very
      sensitive method is required to detect it. In this regard, mass spectrometry (MS)
      methods are the best choice. Since TTX is a very polar compound, there will be
      lack of retention on conventional reverse-phase columns; use of ion pair reagent
      or hydrophilic interaction liquid chromatography (HILIC) can help solve this
      problem. The problem of ion suppression is another challenge in analyzing polar
      compound in biological samples. This review will discuss different MS methods and
      their pros and cons.

PMID- 22163188
TI  - Antioxidant effect of a marine oligopeptide preparation from chum salmon
      (Oncorhynchus keta) by enzymatic hydrolysis in radiation injured mice.
AB  - Marine oligopeptide preparation (MOP) obtained from Chum Salmon (Oncorhynchus
      keta) by the method of enzymatic hydrolysis, has been found to possess a
      radioprotective property through stimulation of the radiation-induced
      immunosuppression. The current study aimed to further investigate the free
      radicals scavenging and antioxidant effects of MOP in radiation injured mice.
      Female ICR mice (6-8 weeks old) were randomly divided into 5 groups, i.e., blank
      control, irradiation control and MOP (0.225, 0.450 and 1.350 g/kg body weight)
      plus an irradiation-treated group. The result revealed that MOP significantly
      increased the white blood cell counts after irradiation, and lessened the
      radiation-induced oxidative damage. These effects may be caused by augmentation
      of the activities of antioxidant enzymes, such as SOD and GSH-Px, reduction of
      the lipid peroxidation (MDA level) in liver, and protection against radiation
      induced apoptosis. Therefore, we propose that MOP be used as an ideal antioxidant
      to alleviate radiation-induced oxidation damage in cancer patients.

PMID- 22163189
TI  - Brominated compounds from marine sponges of the genus Aplysina and a compilation
      of their 13C NMR spectral data.
AB  - Aplysina is the best representative genus of the family Aplysinidae. Halogenated
      substances are its main class of metabolites. These substances contribute greatly
      to the chemotaxonomy and characterization of the sponges belonging to this genus.
      Due to their pharmacological activities, these alkaloids are of special interest.
      The chemistry of halogenated substances and of the alkaloids has long been
      extensively studied in terrestrial organisms, while the number of marine
      organisms studied has just started to increase in the last decades. This review
      describes 101 halogenated substances from 14 species of Aplysina from different
      parts of the world. These substances can be divided into the following classes:
      bromotyramines (A), cavernicolins (B), hydroverongiaquinols (C),
      bromotyrosineketals (D), bromotyrosine lactone derivatives (E), oxazolidones (F),
      spiroisoxazolines (G), verongiabenzenoids (H), verongiaquinols (I), and
      dibromocyclohexadienes (J). A compilation of their (13)C NMR data is also part of
      the review. For this purpose 138 references were consulted.

PMID- 22163190
TI  - 4-Acetoxydolastane diterpene from the Brazilian brown alga Canistrocarpus
      cervicornis as antileishmanial agent.
AB  - Natural marine products have shown an interesting array of diverse and novel
      chemical structures with potent biological activities. Our study reports the
      antiproliferative assays of crude extracts, fraction and pure compound
      (4R,9S,14S)-4alpha-acetoxy-9beta,14alpha-dihydroxydolast-1(15),7-diene (1)
      obtained from brown alga Canistrocarpus cervicornis showing the antileishmanial
      activity. We showed that 1 had a dose-dependent activity during 72 h of
      treatment, exhibiting IC(50) of 2.0 MUg/mL, 12.0 MUg/mL, and 4.0 MUg/mL for
      promastigote, axenic amastigote and intracellular amastigote forms of Leishmania
      amazonensis, respectively. A cytotoxicity assay showed that the action of the
      isolated compound 1 was 93.0 times less toxic to the macrophage than to the
      protozoan. Additionally, compound 1 induced ultrastructural changes, including
      extensive mitochondrial damage; decrease in Rh123 fluorescence, suggesting
      interference with the mitochondrial membrane potential; and lipid peroxidation in
      parasite cells. The use of 1 from C. cervicornis against L. amazonensis parasites
      might be of great interest as a future alternative to the development of new
      antileishmanial drugs.

PMID- 22163191
TI  - Isolation and identification of a new tetrodotoxin-producing bacterial species,
      Raoultella terrigena, from Hong Kong marine puffer fish Takifugu niphobles.
AB  - Puffer fish, Takifugu niphobles, collected from the Hong Kong coastal waters were
      screened for tetrodotoxin-producing bacteria. A Gram-negative, non-acid-fast, non
      sporing and rod shaped bacterial strain (designated as gutB01) was isolated from
      the intestine of the puffer fish and was shown to produce tetrodotoxin (TTX).
      Based on the Microbial Identification (MIDI) and 16S-23S rDNA internal
      transcribed spacer (ITS) phylogenetic analysis, the strain was identified as
      Raoultella terrigena. The TTX production ability of the strain was confirmed by
      mouse bioassay, ELISA and mass spectrometry (MALDI-TOF). Our results reiterate
      that the TTX found in puffer fish was likely produced by the associated bacteria
      and TTX are widely produced amongst a diversity of bacterial species.

PMID- 22163192
TI  - Neoamphimedine circumvents metnase-enhanced DNA topoisomerase IIalpha activity
      through ATP-competitive inhibition.
AB  - Type IIalpha DNA topoisomerase (TopoIIalpha) is among the most important clinical
      drug targets for the treatment of cancer. Recently, the DNA repair protein
      Metnase was shown to enhance TopoIIalpha activity and increase resistance to
      TopoIIalpha poisons. Using in vitro DNA decatenation assays we show that
      neoamphimedine potently inhibits TopoIIalpha-dependent DNA decatenation in the
      presence of Metnase. Cell proliferation assays demonstrate that neoamphimedine
      can inhibit Metnase-enhanced cell growth with an IC(50) of 0.5 MUM. Additionally,
      we find that the apparent K(m) of TopoIIalpha for ATP increases linearly with
      higher concentrations of neoamphimedine, indicating ATP-competitive inhibition,
      which is substantiated by molecular modeling. These findings support the
      continued development of neoamphimedine as an anticancer agent, particularly in
      solid tumors that over-express Metnase.

PMID- 22163193
TI  - Tetrodotoxin sensitivity of the vertebrate cardiac Na+ current.
AB  - Evolutionary origin and physiological significance of the tetrodotoxin (TTX)
      resistance of the vertebrate cardiac Na(+) current (I(Na)) is still unresolved.
      To this end, TTX sensitivity of the cardiac I(Na) was examined in cardiac
      myocytes of a cyclostome (lamprey), three teleost fishes (crucian carp, burbot
      and rainbow trout), a clawed frog, a snake (viper) and a bird (quail). In
      lamprey, teleost fishes, frog and bird the cardiac I(Na) was highly TTX-sensitive
      with EC(50)-values between 1.4 and 6.6 nmol.L(-1). In the snake heart, about 80%
      of the I(Na) was TTX-resistant with EC(50) value of 0.65 MUmol.L(-1), the rest
      being TTX-sensitive (EC(50) = 0.5 nmol.L(-1)). Although TTX-resistance of the
      cardiac I(Na) appears to be limited to mammals and reptiles, the presence of TTX
      resistant isoform of Na(+) channel in the lamprey heart suggest an early
      evolutionary origin of the TTX-resistance, perhaps in the common ancestor of all
      vertebrates.

PMID- 22163194
TI  - Advancement into the Arctic region for bioactive sponge secondary metabolites.
AB  - Porifera have long been a reservoir for the discovery of bioactive compounds and
      drug discovery. Most research in the area has focused on sponges from tropical
      and temperate waters, but more recently the focus has shifted to the less
      accessible colder waters of the Antarctic and, to a lesser extent, the Arctic.
      The Antarctic region in particular has been a more popular location for natural
      products discovery and has provided promising candidates for drug development.
      This article reviews groups of bioactive compounds that have been isolated and
      reported from the southern reaches of the Arctic Circle, surveys the known sponge
      diversity present in the Arctic waters, and details a recent sponge collection by
      our group in the Aleutian Islands, Alaska. The collection has yielded previously
      undescribed sponge species along with primary activity against opportunistic
      infectious diseases, malaria, and HCV. The discovery of new sponge species and
      bioactive crude extracts gives optimism for the isolation of new bioactive
      compounds from a relatively unexplored source.

PMID- 22163195
TI  - Variability of non-polar secondary metabolites in the red alga Portieria.
AB  - Possible sources of variation in non-polar secondary metabolites of Portieria
      hornemannii, sampled from two distinct regions in the Philippines (Batanes and
      Visayas), resulting from different life-history stages, presence of cryptic
      species, and/or spatiotemporal factors, were investigated. PCA analyses
      demonstrated secondary metabolite variation between, as well as within, five
      cryptic Batanes species. Intraspecific variation was even more pronounced in the
      three cryptic Visayas species, which included samples from six sites. Neither
      species groupings, nor spatial or temporal based patterns, were observed in the
      PCA analysis, however, intraspecific variation in secondary metabolites was
      detected between life-history stages. Male gametophytes (102 metabolites
      detected) were strongly discriminated from the two other stages, whilst female
      gametophyte (202 metabolites detected) and tetrasporophyte (106 metabolites
      detected) samples were partially discriminated. These results suggest that life
      history driven variations, and possibly other microscale factors, may influence
      the variation within Portieria species.

PMID- 22163196
TI  - A new diketopiperazine, cyclo-(4-S-hydroxy-R-proline-R-isoleucine), from an
      Australian specimen of the sponge Stelletta sp.
AB  - While investigating the cytotoxic activity of the methanol extract of an
      Australian marine sponge Stelletta sp. (Demospongiae), a new diketopiperazine,
      cyclo-(4-S-hydroxy-R-proline-R-isoleucine) (1), was isolated together with the
      known bengamides; A (2), F (3), N (4), Y (5), and bengazoles; Z (6), C(4) (7) and
      C(6) (8). The isolation and structure elucidation of the diketopiperazine (1),
      together with the activity of 1-8 against a panel of human and mammalian cell
      lines are discussed.

PMID- 22163197
TI  - Alkaloids and sesquiterpenes from the South China Sea gorgonian Echinogorgia
      pseudossapo.
AB  - Five zoanthoxanthin alkaloids (1-5) and four sesquiterpenes (6-9) were isolated
      from the South China Sea gorgonian Echinogorgia pseudossapo. Their structures
      were determined on the bases of extensive spectroscopic analyses, including 1D
      and 2D NMR data. Among them, pseudozoanthoxanthins III and IV (1-2), 8-hydroxy
      6beta-methoxy-14- oxooplop-6,12-olide (6) and 3beta-methoxyguaian-10(14)-en-2beta
      ol (7) were new, 1 and 3 showed mild anti-HSV-1 activity, and 7 showed
      significant antilarval activity towards Balanus amphitrite larvae.

PMID- 22163198
TI  - Effects of tobacco taxation and pricing on smoking behavior in high risk
      populations: a knowledge synthesis.
AB  - Tobacco taxation is an essential component of a comprehensive tobacco control
      strategy. However, to fully realize the benefits it is vital to understand the
      impact of increased taxes among high-risk subpopulations. Are they influenced to
      the same extent as the general population? Do they need additional measures to
      influence smoking behavior? The objectives of this study were to synthesize the
      evidence regarding differential effects of taxation and price on smoking in:
      youth, young adults, persons of low socio-economic status, with dual diagnoses,
      heavy/long-term smokers, and Aboriginal people. Using a better practices
      approach, a knowledge synthesis was conducted using a systematic review of the
      literature and an expert advisory panel. Experts were involved in developing the
      study plan, discussing findings, developing policy recommendations, and
      identifying priorities for future research. Most studies found that raising
      cigarette prices through increased taxes is a highly effective measure for
      reducing smoking among youth, young adults, and persons of low socioeconomic
      status. However, there is a striking lack of evidence about the impact of
      increasing cigarette prices on smoking behavior in heavy/long-term smokers,
      persons with a dual diagnosis and Aboriginals. Given their high prevalence of
      smoking, urgent attention is needed to develop effective policies for the six
      subpopulations reviewed. These findings will be of value to policy-makers and
      researchers in their efforts to improve the effectiveness of tobacco control
      measures, especially with subpopulations at most risk. Although specific studies
      are needed, tobacco taxation is a key policy measure for driving success.

PMID- 22163199
TI  - Cumulative risk assessment and environmental equity in air permitting:
      interpretation, methods, community participation and implementation of a unique
      statute.
AB  - In 2008, the statute authorizing the Minnesota Pollution Control Agency (MPCA) to
      issue air permits was amended to include a unique requirement to analyze and
      consider "cumulative levels and effects of past and current environmental
      pollution from all sources on the environment and residents of the geographic
      area within which the facility's emissions are likely to be deposited." Data
      describing the Statute Area suggest it is challenged by environmental and
      socioeconomic concerns, i.e., concerns which are often described by the phrase
      'environmental equity'. With input from diverse stakeholders, the MPCA developed
      a methodology for implementing a cumulative levels and effects analysis when
      issuing air permits in the designated geographic area. A Process Document was
      created defining explicit steps a project proposer must complete in the analysis.
      An accompanying Reference Document compiles all available environmental health
      data relevant to the Statute Area that could be identified. The final cumulative
      levels and effects methodology is organized by health endpoint and identifies
      hazard, exposure and health indices that require further evaluation. The
      resulting assessment is summarized and presented to decision makers for
      consideration in the regulatory permitting process. We present a description of
      the methodology followed by a case study summary of the first air permit
      processed through the "cumulative levels and effects analysis".

PMID- 22163200
TI  - Validation of walk score for estimating neighborhood walkability: an analysis of
      four US metropolitan areas.
AB  - Neighborhood walkability can influence physical activity. We evaluated the
      validity of Walk Score((r)) for assessing neighborhood walkability based on GIS
      (objective) indicators of neighborhood walkability with addresses from four US
      metropolitan areas with several street network buffer distances (i.e., 400-, 800
      , and 1,600-meters). Address data come from the YMCA-Harvard After School Food
      and Fitness Project, an obesity prevention intervention involving children aged 5
      11 years and their families participating in YMCA-administered, after-school
      programs located in four geographically diverse metropolitan areas in the US (n =
      733). GIS data were used to measure multiple objective indicators of neighborhood
      walkability. Walk Scores were also obtained for the participant's residential
      addresses. Spearman correlations between Walk Scores and the GIS neighborhood
      walkability indicators were calculated as well as Spearman correlations
      accounting for spatial autocorrelation. There were many significant moderate
      correlations between Walk Scores and the GIS neighborhood walkability indicators
      such as density of retail destinations and intersection density (p < 0.05). The
      magnitude varied by the GIS indicator of neighborhood walkability. Correlations
      generally became stronger with a larger spatial scale, and there were some
      geographic differences. Walk Score((r)) is free and publicly available for public
      health researchers and practitioners. Results from our study suggest that Walk
      Score((r)) is a valid measure of estimating certain aspects of neighborhood
      walkability, particularly at the 1600-meter buffer. As such, our study confirms
      and extends the generalizability of previous findings demonstrating that Walk
      Score is a valid measure of estimating neighborhood walkability in multiple
      geographic locations and at multiple spatial scales.

PMID- 22163201
TI  - MATES in construction: impact of a multimodal, community-based program for
      suicide prevention in the construction industry.
AB  - A large-scale workplace-based suicide prevention and early intervention program
      was delivered to over 9,000 construction workers on building sites across
      Queensland. Intervention components included universal General Awareness Training
      (GAT; general mental health with a focus on suicide prevention); gatekeeper
      training provided to construction worker volunteer 'Connectors'; Suicide First
      Aid (ASIST) training offered to key workers; outreach support provided by trained
      and supervised MIC staff; state-wide suicide prevention hotline; case management
      service; and postvention support provided in the event of a suicide. Findings
      from over 7,000 workers (April 2008 to November 2010) are reported, indicating
      strong construction industry support, with 67% building sites and employers
      approached agreeing to participate in MIC. GAT participants demonstrated
      significantly increased suicide prevention awareness compared with a comparison
      group. Connector training participants rated MIC as helpful and effective, felt
      prepared to intervene with a suicidal person, and knew where to seek help for a
      suicidal individual following the training. Workers engaged positively with the
      after-hours crisis support phone line and case management. MIC provided
      postvention support to 10 non-MIC sites and sites engaged with MIC, but not yet
      MIC-compliant. Current findings support the potential effectiveness and social
      validity of MIC for preventing suicide in construction workers.

PMID- 22163202
TI  - Influenza vaccination among adults 65 years or older: a 2009-2010 community
      health survey in the Honam region of Korea.
AB  - The present study examined the rates and related factors for influenza
      vaccination among the elderly Korean population during the 2008/09 influenza
      seasons. We obtained data for 6,391 adults aged 65 years or older from Community
      Health Surveys conducted in 2009 and 2010 in 13 communities in the Honam region
      of Korea. A multiple logistic regression analysis was used to identify the
      factors associated with self-reported influenza vaccinations. In this elderly
      population, 81.7% reported to having received an influenza vaccination in the
      past year. The main contributing factors were older age, lower economic status,
      lower educational level, married, non-smoking, regular alcohol consumption,
      regular walking exercise, receiving a health check-up during the past two years,
      not stressed, and having comorbid conditions. The influenza vaccination coverage
      rate among elderly Koreans was relatively high, but improvements in vaccination
      rates are required.

PMID- 22163203
TI  - Knowledge, attitudes, and behavior in avoiding secondhand smoke exposure among
      non-smoking employed women with higher education in Jordan.
AB  - Secondhand smoke (SHS) exposure is a serious public health threat worldwide; in
      the developing world there are less serious efforts towards controlling women's
      and children's exposure to SHS. Knowledge, attitudes and avoidance practices
      among Jordanian women have never been thoroughly studied. The purpose of this
      study was to assess the knowledge, attitudes, and avoidance behavior towards SHS
      exposure among employed Jordanian women with higher education. METHODS: A survey
      was conducted among employed Jordanian women at two universities. A total of 209
      women were included in the analysis. Two questionnaires regarding SHS exposure
      were used to measure knowledge, attitudes and avoidance practices. RESULTS: Most
      respondents were regularly exposed to SHS in various locations during daily life,
      even though they were very knowledgeable about the dangers of SHS exposure for
      women and children. However, the subject's attitudes and avoidance behavior did
      not reflect the level of knowledge about SHS risks. The results suggests there is
      a large discrepancy between SHS exposure, knowledge, attitudes and avoidance
      behavior among highly educated Jordanian women that is likely influenced by
      culture and traditional gender roles. Public health initiatives are needed in
      Jordan to address public policy, institutional practices and to empowerment of
      women to reduce SHS exposure.

PMID- 22163204
TI  - A methodological approach to assessing the health impact of environmental
      chemical mixtures: PCBs and hypertension in the National Health and Nutrition
      Examination Survey.
AB  - We describe an approach to examine the association between exposure to chemical
      mixtures and a health outcome, using as our case study polychlorinated biphenyls
      (PCBs) and hypertension. The association between serum PCB and hypertension among
      participants in the 1999-2004 National Health and Nutrition Examination Survey
      was examined. First, unconditional multivariate logistic regression was used to
      estimate odds ratios and associated 95% confidence intervals. Next, correlation
      and multicollinearity among PCB congeners was evaluated, and clustering analyses
      performed to determine groups of related congeners. Finally, a weighted sum was
      constructed to represent the relative importance of each congener in relation to
      hypertension risk. PCB serum concentrations varied by demographic
      characteristics, and were on average higher among those with hypertension.
      Logistic regression results showed mixed findings by congener and class. Further
      analyses identified groupings of correlated PCBs. Using a weighted sum approach
      to equalize different ranges and potencies, PCBs 66, 101, 118, 128 and 187 were
      significantly associated with increased risk of hypertension. Epidemiologic data
      were used to demonstrate an approach to evaluating the association between a
      complex environmental exposure and health outcome. The complexity of analyzing a
      large number of related exposures, where each may have different potency and
      range, are addressed in the context of the association between hypertension risk
      and exposure to PCBs.

PMID- 22163205
TI  - Trichloroethylene and cancer: systematic and quantitative review of epidemiologic
      evidence for identifying hazards.
AB  - We conducted a meta-analysis focusing on studies with high potential for
      trichloroethylene (TCE) exposure to provide quantitative evaluations of the
      evidence for associations between TCE exposure and kidney, liver, and non-Hodgkin
      lymphoma (NHL) cancers. A systematic review documenting essential design
      features, exposure assessment approaches, statistical analyses, and potential
      sources of confounding and bias identified twenty-four cohort and case-control
      studies on TCE and the three cancers of interest with high potential for
      exposure, including five recently published case-control studies of kidney cancer
      or NHL. Fixed- and random-effects models were fitted to the data on overall
      exposure and on the highest exposure group. Sensitivity analyses examined the
      influence of individual studies and of alternative risk estimate selections. For
      overall TCE exposure and kidney cancer, the summary relative risk (RRm) estimate
      from the random effects model was 1.27 (95% CI: 1.13, 1.43), with a higher RRm
      for the highest exposure groups (1.58, 95% CI: 1.28, 1.96). The RRm estimates
      were not overly sensitive to alternative risk estimate selections or to removal
      of an individual study. There was no apparent heterogeneity or publication bias.
      For NHL, RRm estimates for overall exposure and for the highest exposure group,
      respectively, were 1.23 (95% CI: 1.07, 1.42) and 1.43 (95% CI: 1.13, 1.82) and,
      for liver cancer, 1.29 (95% CI: 1.07, 1.56) and 1.28 (95% CI: 0.93, 1.77). Our
      findings provide strong support for a causal association between TCE exposure and
      kidney cancer. The support is strong but less robust for NHL, where issues of
      study heterogeneity, potential publication bias, and weaker exposure-response
      results contribute uncertainty, and more limited for liver cancer, where only
      cohort studies with small numbers of cases were available.

PMID- 22163206
TI  - Estimation of effective day length at any light intensity using solar radiation
      data.
AB  - The influence of day length on living creatures differs with the photosensitivity
      of the creature; however, the possible sunshine duration (N(0)) might be an
      inadequate index of the photoperiod for creatures with low light sensitivity. To
      address this issue, the authors tried to estimate the effective day length, i.e.,
      the duration of the photoperiod that exceeds a certain threshold of light
      intensity. Continual global solar radiation observation data were gathered from
      the baseline surface radiation network (BSRN) of 18 sites from 2004 to 2007 and
      were converted to illuminance data using a luminous efficiency model. The monthly
      average of daily photoperiods exceeding each defined intensity (1 lx, 300 lx, ...
      20,000 lx) were calculated [defined as Ne(() (lux) ())]. The relationships
      between the monthly average of global solar radiation (Rs), N(0), and Ne(() (lux)
      ()) were investigated. At low light intensity (<500 lx), Ne(() (lux) ()) were
      almost the same as N(0). At high light intensity (>10,000 lx), Ne(() (lux) ())
      and Rs showed a logarithmic relationship. Using these relationships, empirical
      models were derived to estimate the effective day length at different light
      intensities. According to the validation of the model, the effective day length
      for any light intensity could be estimated with an accuracy of less than 11% of
      the mean absolute percentage error (MAPE) in the estimation of the monthly base
      photoperiod. Recently, a number of studies have provided support for a link
      between day length and some diseases. Our results will be useful in further
      assessing the relationships between day length and these diseases.

PMID- 22163207
TI  - Association between socioeconomic factors and the choice of dentifrice and
      fluoride intake by children.
AB  - It is questionable whether socioeconomic factors influence the choice of marketed
      children's dentifrices and whether these products are associated with greater
      fluoride (F) intake in children. The present cross-sectional study involving 197
      children (mean age: 40.98 +/- 6.62 months) was carried out in Montes Claros,
      Brazil. Parents completed a questionnaire on socioeconomic status and the tooth
      brushing habits of their children. The children brushed their teeth and saliva
      residues were collected for F analysis. F intake from dentifrice was determined
      with an ion-specific electrode. Univariate analysis and logistic regression were
      used to test whether the type of dentifrice (children's or family) and F dose
      (<0.05 and >=0.05 mg F/Kg of body weight/day) were associated with the
      independent variables (p < 0.05). No differences were found between children's
      and family dentifrices regarding daily F intake (0.046 and 0.040 mg F/Kg/day,
      respectively; p = 0.513). The following were strong predictors for the use of a
      children's dentifrice: studying at a private kindergarten (OR: 6.89; p < 0.001);
      age that the child begun to tooth brush <2 years (OR: 2.93; p = 0.041), and the
      interaction between the variables "use of the same dentifrice as parents" and
      "type of tooth brush used" (OR: 27.20; p < 0.001). "The amount of dentifrice
      used" and "frequency of tooth brushing" (p <= 0.004) had a statistically and
      synergistic effect over the daily F dose. The present study found a social
      influence over the choice of dentifrice: children with a high socioeconomic
      status tend to use a children's dentifrice. The amount of dentifrice used can
      strongly increase the risk of exposure to higher doses of F, regardless of the
      type of dentifrice.

PMID- 22163208
TI  - Physician consultations according to different BMI levels of the Greek general
      population.
AB  - Obesity constitutes a global epidemic which is rapidly becoming a major public
      health problem in many parts of the world, threatening peoples' health and
      quality of life. The aim of our study was to estimate the prevalence and impact
      of overweight and obesity on physician consultations and frequency of use and
      furthermore, to investigate whether physician consultations in each of the groups
      defined by BMI level correspond to the need for care implied by health risk
      level, using logistic regression models. The survey was carried out in Greece in
      2006 and involved complete data from 645 individuals consulted by physicians.
      Overweight and obese users constituted 41.7% and 19% of the sample respectively.
      The findings showed firstly that the odds of obese individuals visiting a
      physician (OR 2.15) or making more than three visits (OR 2.12) was doubled
      compared to the odds of individuals with normal weight. Secondly, we conclude
      that physician consultations in overweight and obese subgroups as well as the
      frequency of visits were predicted by factors such as co-morbidities, low HRQL,
      low educational level which are associated directly or indirectly with obesity,
      and thus with a greater health need, assuming vertical equity in the utilization
      of such services.

PMID- 22163209
TI  - Implementation of the framework convention on tobacco control in Africa: current
      status of legislation.
AB  - OBJECTIVE: To describe, as of July 2011, the status of tobacco control
      legislation in Africa in three key areas of the Framework Convention on Tobacco
      Control (FCTC)-(1) Protection from exposure to tobacco smoke, (2) Packaging and
      labelling of tobacco products, and (3) Tobacco advertising, promotion and
      sponsorship. METHODS: Review and analysis of tobacco control legislation in
      Africa, media reports, journal articles, tobacco industry documents and data
      published in the 2011 WHO Report on the Global Tobacco Epidemic. RESULTS: Modest
      progress in FCTC implementation in Africa with many countries having legislation
      or policies on the protection from exposure to tobacco smoke, however, only a
      handful of countries meet the standards of the FCTC Article 8 and its Guidelines
      particularly with regards to designated smoking areas. Little progress on
      packaging and labelling of tobacco products, with few countries having
      legislation meeting the minimum standards of the FCTC Article 11 and its
      Guidelines. Mauritius is the only African country with graphic or pictorial
      health warnings in place and has the largest warning labels in Africa. Slightly
      better progress in banning tobacco advertising, promotion and sponsorship has
      been shown by African countries, although the majority of legislation falls short
      of the standards of the FCTC Article 13 and its Guidelines. Despite their
      efforts, African countries' FCTC implementation at national level has not matched
      the strong regional commitment demonstrated during the FCTC treaty negotiations.
      CONCLUSION: This study highlights the need for Africa to step up efforts to adopt
      and implement effective tobacco control legislation that is fully compliant with
      the FCTC. In order to achieve this, countries should prioritise resources for
      capacity building for drafting strong FCTC compliant legislation, research to
      inform policy and boost political will, and countering the tobacco industry which
      is a major obstacle to FCTC implementation in Africa.

PMID- 22163210
TI  - Assessment of water quality in Asa River (Nigeria) and its indigenous Clarias
      gariepinus fish.
AB  - Water is a valued natural resource for the existence of all living organisms.
      Management of the quality of this precious resource is, therefore, of special
      importance. In this study river water samples were collected and analysed for
      physicochemical and bacteriological evaluation of pollution in the Unity Road
      stream segment of Asa River in Ilorin, Nigeria. Juvenile samples of Clarias
      gariepinus fish were also collected from the experimental Asa River and from the
      control Asa Dam water and were analysed for comparative histological
      investigations and bacterial density in the liver and intestine in order to
      evaluate the impact of pollution on the aquatic biota. The water pH was found to
      range from 6.32 to 6.43 with a mean temperature range of 24.3 to 25.8  degrees C.
      Other physicochemical parameters monitored including total suspended solids,
      total dissolved solids, biochemical oxygen demand and chemical oxygen demand
      values exceeded the recommended level for surface water quality. Results of
      bacteriological analyses including total heterotrophic count, total coliform and
      thermotolerant coliform counts revealed a high level of faecal pollution of the
      river. Histological investigations revealed no significant alterations in tissue
      structure, but a notable comparative distinction of higher bacterial density in
      the intestine and liver tissues of Clarias gariepinus from Asa River than in
      those collected from the control. It was inferred that the downstream Asa River
      is polluted and its aquatic biota is bacteriologically contaminated and unsafe
      for human and animal consumption.

PMID- 22163211
TI  - Malnutrition in the critically ill child: the importance of enteral nutrition.
AB  - Malnutrition affects 50% of hospitalized children and 25-70% of the critically
      ill children. It increases the incidence of complications and mortality.
      Malnutrition is associated with an altered metabolism of certain substrates,
      increased metabolism and catabolism depending on the severity of the lesion, and
      reduced nutrient delivery. The objective should be to administer individualized
      nutrition to the critically ill child and to be able to adjust the nutrition
      continuously according to the metabolic changes and evolving nutritional status.
      It would appear reasonable to start enteral nutrition within the first 24 to 48
      hours after admission, when oral feeding is not possible. Parenteral nutrition
      should only be used when enteral nutrition is contraindicated or is not
      tolerated. Energy delivery must be individually adjusted to energy expenditure
      (40-65 kcal/100 calories metabolized/day) with a protein delivery of 2.5-3
      g/kg/day. Frequent monitoring of nutritional and metabolic parameters should be
      performed.

PMID- 22163212
TI  - Regionalizing aquatic ecosystems based on the river subbasin taxonomy concept and
      spatial clustering techniques.
AB  - Aquatic ecoregions were increasingly used as spatial units for aquatic ecosystem
      management at the watershed scale. In this paper, the principle of including land
      area, comprehensiveness and dominance, conjugation and hierarchy were selected as
      regionalizing principles. Elevation and drainage density were selected as the
      regionalizing indicators for the delineation of level I aquatic ecoregions, and
      percent of construction land area, percent of cultivated land area, soil type and
      slope for the level II. Under the support of GIS technology, the spatial
      distribution maps of the two indicators for level I and the four indicators for
      level II aquatic ecoregion delineation were generated from the raster data based
      on the 1,107 subwatersheds. River subbasin taxonomy concept, two-step spatial
      clustering analysis approach and manual-assisted method were used to regionalize
      aquatic ecosystems in the Taihu Lake watershed. Then the Taihu Lake watershed was
      divided into two level I aquatic ecoregions, including Ecoregion I1 and Ecoregion
      I2, and five level II aquatic subecoregions, including Subecoregion II11,
      Subecoregion II12, Subecoregion II21, Subecoregion II22 and Subecoregion II23.
      Moreover, the characteristics of the two level I aquatic ecoregions and five
      level II aquatic subecoregions in the Taihu Lake watershed were summarized,
      showing that there were significant differences in topography, socio-economic
      development, water quality and aquatic ecology, etc. The results of quantitative
      comparison of aquatic life also indicated that the dominant species of fish,
      benthic density, biomass, dominant species, Shannon-Wiener diversity index,
      Margalef species richness index, Pielou evenness index and ecological dominance
      showed great spatial variability between the two level I aquatic ecoregions and
      five level II aquatic subecoregions. It reflected the spatial heterogeneities and
      the uneven natures of aquatic ecosystems in the Taihu Lake watershed.

PMID- 22163213
TI  - Tunable neuromimetic integrated system for emulating cortical neuron models.
AB  - Nowadays, many software solutions are currently available for simulating neuron
      models. Less conventional than software-based systems, hardware-based solutions
      generally combine digital and analog forms of computation. In previous work, we
      designed several neuromimetic chips, including the Galway chip that we used for
      this paper. These silicon neurons are based on the Hodgkin-Huxley formalism and
      they are optimized for reproducing a large variety of neuron behaviors thanks to
      tunable parameters. Due to process variation and device mismatch in analog chips,
      we use a full-custom fitting method in voltage-clamp mode to tune our
      neuromimetic integrated circuits. By comparing them with experimental
      electrophysiological data of these cells, we show that the circuits can reproduce
      the main firing features of cortical cell types. In this paper, we present the
      experimental measurements of our system which mimic the four most prominent
      biological cells: fast spiking, regular spiking, intrinsically bursting, and low
      threshold spiking neurons into analog neuromimetic integrated circuit dedicated
      to cortical neuron simulations. This hardware and software platform will allow to
      improve the hybrid technique, also called "dynamic-clamp," that consists of
      connecting artificial and biological neurons to study the function of neuronal
      circuits.

PMID- 22163214
TI  - Alterations in Apical Dendrite Bundling in the Somatosensory Cortex of 5-HT(3A)
      Receptor Knockout Mice.
AB  - In various species and areas of the cerebral cortex, apical dendrites of
      pyramidal neurons form clusters which extend through several layers of the cortex
      also known as dendritic bundles. Previously, it has been shown that 5-HT(3A)
      receptor knockout mice show hypercomplex apical dendrites of cortical layer 2/3
      pyramidal neurons, together with a reduction in reelin levels, a glycoprotein
      involved in cortical development. Other studies showed that in the mouse
      presubicular cortex, reelin is involved in the formation of modular structures.
      Here, we compare apical dendrite bundling in the somatosensory cortex of wildtype
      and 5-HT(3A) receptor knockout mice. Using a microtubule associated protein-2
      immunostaining to visualize apical dendrites of pyramidal neurons, we compared
      dendritic bundle properties of wildtype and 5-HT(3A) receptor knockout mice in
      tangential sections of the somatosensory cortex. A Voronoi tessellation was
      performed on immunostained tangential sections to determine the spatial
      organization of dendrites and to define dendritic bundles. In 5-HT(3A) receptor
      knockout mice, dendritic bundle surface was larger compared to wildtype mice,
      while the number and distribution of reelin-secreting Cajal-Retzius cells was
      similar for both groups. Together with previously observed differences in
      dendritic complexity of cortical layer 2/3 pyramidal neurons and cortical reelin
      levels, these results suggest an important role for the 5-HT(3) receptor in
      determining the spatial organization of cortical connectivity in the mouse
      somatosensory cortex.

PMID- 22163216
TI  - Learning and the development of contexts for action.
AB  - Neurophysiological evidence from animal studies suggests that frontal
      corticolimbic systems support early stages of learning, whereas later stages
      involve context representation formed in hippocampus and posterior cingulate
      cortex. In dense-array EEG studies of human learning, we observed brain activity
      in medial prefrontal cortex (the medial frontal negativity or MFN) was not only
      observed in early stages, but, surprisingly, continued to increase as learning
      progressed. In the present study we investigated this finding by examining MFN
      amplitude as participants learned an arbitrary associative learning task over
      three sessions. On the fourth session the same task with new stimuli was
      presented to assess changes in MFN amplitude. The results showed that MFN
      amplitude continued to increase with practice over the first three sessions, in
      contrast to P3 amplitudes. Even when participants were presented with new stimuli
      in session 4, MFN amplitude was larger than that observed in the first session.
      Furthermore, MFN activity from the third session predicted learning rate in the
      fourth session. The results point to an interaction between early and late stages
      in which learning results in corticolimbic consolidation of cognitive context
      models that facilitate new learning in similar contexts.

PMID- 22163215
TI  - Behavioral and neurophysiological study of olfactory perception and learning in
      honeybees.
AB  - The honeybee Apis mellifera has been a central insect model in the study of
      olfactory perception and learning for more than a century, starting with pioneer
      work by Karl von Frisch. Research on olfaction in honeybees has greatly benefited
      from the advent of a range of behavioral and neurophysiological paradigms in the
      Lab. Here I review major findings about how the honeybee brain detects,
      processes, and learns odors, based on behavioral, neuroanatomical, and
      neurophysiological approaches. I first address the behavioral study of olfactory
      learning, from experiments on free-flying workers visiting artificial flowers to
      laboratory-based conditioning protocols on restrained individuals. I explain how
      the study of olfactory learning has allowed understanding the discrimination and
      generalization ability of the honeybee olfactory system, its capacity to grant
      special properties to olfactory mixtures as well as to retain individual
      component information. Next, based on the impressive amount of anatomical and
      immunochemical studies of the bee brain, I detail our knowledge of olfactory
      pathways. I then show how functional recordings of odor-evoked activity in the
      brain allow following the transformation of the olfactory message from the
      periphery until higher-order central structures. Data from extra- and
      intracellular electrophysiological approaches as well as from the most recent
      optical imaging developments are described. Lastly, I discuss results addressing
      how odor representation changes as a result of experience. This impressive
      ensemble of behavioral, neuroanatomical, and neurophysiological data available in
      the bee make it an attractive model for future research aiming to understand
      olfactory perception and learning in an integrative fashion.

PMID- 22163217
TI  - Vibrotactile working memory as a model paradigm for psychology, neuroscience, and
      computational modeling.

PMID- 22163218
TI  - An instruction language for self-construction in the context of neural networks.
AB  - Biological systems are based on an entirely different concept of construction
      than human artifacts. They construct themselves by a process of self-organization
      that is a systematic spatio-temporal generation of, and interaction between,
      various specialized cell types. We propose a framework for designing gene-like
      codes for guiding the self-construction of neural networks. The description of
      neural development is formalized by defining a set of primitive actions taken
      locally by neural precursors during corticogenesis. These primitives can be
      combined into networks of instructions similar to biochemical pathways, capable
      of reproducing complex developmental sequences in a biologically plausible way.
      Moreover, the conditional activation and deactivation of these instruction
      networks can also be controlled by these primitives, allowing for the design of a
      "genetic code" containing both coding and regulating elements. We demonstrate in
      a simulation of physical cell development how this code can be incorporated into
      a single progenitor, which then by replication and differentiation, reproduces
      important aspects of corticogenesis.

PMID- 22163219
TI  - Formation of Essential Ultrastructural Interface between Cultured Hippocampal
      Cells and Gold Mushroom-Shaped MEA- Toward "IN-CELL" Recordings from Vertebrate
      Neurons.
AB  - Using cultured Aplysia neurons we recently reported on the development of a novel
      approach in which an extracellular, non-invasive multi-electrode-array system
      provides multisite, attenuated, intracellular recordings of subthreshold synaptic
      potentials, and action potentials (APs), the so called "IN-CELL" recording
      configuration (to differentiate it from intracellular recordings). Because of its
      non-invasive nature, the configuration can be used for long term semi
      intracellular electrophysiological monitoring of APs and synaptic potentials.
      Three principals converge to generate the IN-CELL configuration: (a) engulfment
      of approximately 1 MUm size gold mushroom-shaped microelectrodes (gMMUE) by the
      neurons, (b) formation of high seal resistance between the cell's plasma membrane
      and the engulfed gMMUE, and (c), autonomous localized increased conductance of
      the membrane patch facing the gMMUE. Using dissociated rat hippocampal cultures
      we report here that the necessary morphological and ultrastructural relationships
      to generate the IN-CELL recording configuration are formed between hippocampal
      cells and the gMMUEs. Interestingly, even <1 MUm thin branches expand and engulf
      the gMMUE structures. Recordings of spontaneous electrical activity revealed fast
      ~2 ms, 0.04-0.75 mV positive monophasic APs (FPMP). We propose that the FPMP are
      attenuated APs generated by neurons that engulf gMMUEs. Computer simulations of
      analog electrical circuits depicting the cell-gMMUE configuration point out the
      parameters that should be altered to improve the neuron-gMMUE electrical
      coupling.

PMID- 22163220
TI  - Modeling of a segmented electrode for desynchronizing deep brain stimulation.
AB  - Deep brain stimulation (DBS) is an effective therapy for medically refractory
      movement disorders like Parkinson's disease. The electrodes, implanted in the
      target area within the human brain, generate an electric field which activates
      nerve fibers and cell bodies in the vicinity. Even though the different target
      nuclei display considerable differences in their anatomical structure, only few
      types of electrodes are currently commercially available. It is desirable to
      adjust the electric field and in particular the volume of tissue activated around
      the electrode with respect to the corresponding target nucleus in a such way that
      side effects can be reduced. Furthermore, a more selective and partial activation
      of the target structure is desirable for an optimal application of novel
      stimulation strategies, e.g., coordinated reset neuromodulation. Hence we
      designed a DBS electrode with a segmented design allowing a more selective
      activation of the target structure. We created a finite element model (FEM) of
      the electrode and analyzed the volume of tissue activated for this electrode
      design. The segmented electrode activated an area in a targeted manner, of which
      the dimension and position relative to the electrode could be controlled by
      adjusting the stimulation parameters for each electrode contact. According to our
      computational analysis, this directed stimulation might be superior with respect
      to the occurrence of side effects and it enables the application of coordinated
      reset neuromodulation under optimal conditions.

PMID- 22163221
TI  - Somatosensory information processing in the aging population.
AB  - While it is well known that skin physiology - and consequently sensitivity to
      peripheral stimuli - degrades with age, what is less appreciated is that
      centrally mediated mechanisms allow for maintenance of the same degree of
      functionality in processing these peripheral inputs and interacting with the
      external environment. In order to demonstrate this concept, we obtained
      observations of processing speed, sensitivity (thresholds), discriminative
      capacity, and adaptation metrics on subjects ranging in age from 18 to 70. The
      results indicate that although reaction speed and sensory thresholds change with
      age, discriminative capacity, and adaptation metrics do not. The significance of
      these findings is that similar metrics of adaptation have been demonstrated to
      change significantly when the central nervous system (CNS) is compromised. Such
      compromise has been demonstrated in subject populations with autism, chronic
      pain, acute NMDA receptor block, concussion, and with tactile-thermal
      interactions. If the metric of adaptation parallels cortical plasticity, the
      results of the current study suggest that the CNS in the aging population is
      still capable of plastic changes, and this cortical plasticity could be the
      mechanism that compensates for the degradations that are known to naturally occur
      with age. Thus, these quantitative measures - since they can be obtained
      efficiently and objectively, and appear to deviate from normative values
      significantly with systemic cortical alterations - could be useful indicators of
      cerebral cortical health.

PMID- 22163222
TI  - Origin of heart rate variability and turbulence: an appraisal of autonomic
      modulation of cardiovascular function.
AB  - Heart period constantly changes on a beat to beat basis, due to autonomic
      influences on the sinoatrial node, and changes can be quantified as heart rate
      variability (HRV). In addition, after a premature ventricular beat, there are
      reproducible variations in RR interval, also due to baroreflex mediated autonomic
      influences on the sinoatrial node, that can be measured as heart rate turbulence
      (HRT). Impaired autonomic function as measured by HRV and HRT has proven to
      predict adverse outcomes in clinical settings. The ability of reduced HRV and HRT
      to predict adverse outcomes has been explained by their dependency on vagal
      mechanisms that could reflect an increased sympathetic and a reduced vagal
      modulation of sinus node, thus favoring cardiac electrical instability. Analysis
      of non-linear dynamics of HRV has also been utilized to describe the fractal like
      characteristic of the variability signal and proven effective in identify
      patients at risk for sudden cardiac death. Despite the clinical validity of these
      measures, it has also been evident that the relationship between neural input and
      sinus node responsiveness is extremely complex and variable in different clinical
      conditions. Thus, abnormal HRV or HRT on a clinical Holter recordings may reflect
      non-neural as well as autonomic mechanisms, and this also needs to be taken into
      account when interpreting any findings. However, under controlled conditions, the
      computation of the low and high frequency components of HRV and of their
      normalized powers or ratio seems capable of providing valid information on
      sympatho-vagal balance in normal subjects, as well as in most patients with a
      preserved left ventricular function. Thus, analysis of HRV does provide a unique
      tool to specifically assess autonomic control mechanisms in association with
      various perturbations. In conclusion, HRV measures are of substantial utility to
      identify patients with an increased cardiac mortality and to evaluate autonomic
      control mechanisms, but their ability to capture specific levels of autonomic
      control may be limited to controlled laboratory studies in relatively healthy
      subjects.

PMID- 22163223
TI  - Abnormal left-sided orbitomedial prefrontal cortical-amygdala connectivity during
      happy and fear face processing: a potential neural mechanism of female MDD.
AB  - BACKGROUND: Pathophysiologic processes supporting abnormal emotion regulation in
      major depressive disorder (MDD) are poorly understood. We previously found
      abnormal inverse left-sided ventromedial prefrontal cortical-amygdala effective
      connectivity to happy faces in females with MDD. We aimed to replicate and expand
      this previous finding in an independent participant sample, using a more
      inclusive neural model, and a novel emotion processing paradigm. METHODS:
      Nineteen individuals with MDD in depressed episode (12 females), and 19 healthy
      individuals, age, and gender matched, performed an implicit emotion processing
      and automatic attentional control paradigm to examine abnormalities in prefrontal
      cortical-amygdala neural circuitry during happy, angry, fearful, and sad face
      processing measured with functional magnetic resonance imaging in a 3-T scanner.
      Effective connectivity was estimated with dynamic causal modeling in a trinodal
      neural model including two anatomically defined prefrontal cortical regions,
      ventromedial prefrontal cortex, and subgenual cingulate cortex (sgACC), and the
      amygdala. RESULTS: We replicated our previous finding of abnormal inverse left
      sided top-down ventromedial prefrontal cortical-amygdala connectivity to happy
      faces in females with MDD (p = 0.04), and also showed a similar pattern of
      abnormal inverse left-sided sgACC-amygdala connectivity to these stimuli (p =
      0.03). These findings were paralleled by abnormally reduced positive left-sided
      ventromedial prefrontal cortical-sgACC connectivity to happy faces in females
      with MDD (p = 0.008), and abnormally increased positive left-sided sgACC-amygdala
      connectivity to fearful faces in females, and all individuals, with MDD (p =
      0.008; p = 0.003). CONCLUSION: Different patterns of abnormal prefrontal cortical
      amygdala connectivity to happy and fearful stimuli might represent neural
      mechanisms for the excessive self-reproach and comorbid anxiety that characterize
      female MDD.

PMID- 22163224
TI  - Early goal-directed top-down influences in the production of speech.
AB  - It was recently reported that the conscious intention to produce speech affects
      the speed with which lexical information is retrieved upon presentation of an
      object (Strijkers et al., 2011). The goal of the present study was to elaborate
      further on the role of these top-down influences in the course of planning speech
      behavior. In an event-related potentials (ERP) experiment, participants were
      required to overtly name pictures and words in one block of trials, while
      categorizing the same stimuli in another block of trials. The ERPs elicited by
      the naming task started to diverge very early on (~170 ms) from those elicited by
      the semantic categorization task. Interestingly, these early ERP differences
      related to task intentionality were identical for pictures and words. From these
      results we conclude that (a) in line with Strijkers et al. (2011), goal-directed
      processes play a crucial role very early on in speech production, and (b) these
      task-driven top-down influences function at least in a domain-general manner by
      modulating those networks which are always relevant for the production of
      language, irrespective of which cortical pathways are triggered by the input.

PMID- 22163225
TI  - Stenting in the treatment of acute ischemic stroke: literature review.
AB  - Recanalization of acute large artery occlusions is a strong predictor of good
      outcome. The development of thrombectomy devices resulted in a significant
      improvement in recanalization rates compared to thrombolytics alone. However,
      clinical trials and registries with these thrombectomy devices in acute ischemic
      stroke (AIS) have shown recanalization rates in the range of 40-81%. The last
      decade has seen the development of nickel titanium self-expandable stents (SES).
      These stents, in contrast to balloon-mounted stents, allow better navigability
      and deployment in tortuous vessels and therefore are optimal for the cerebral
      circulation. SES were initially used for stent-assisted coil embolization of
      intracranial aneurysms and for treatment of intracranial stenosis. However, a few
      authors have recently reported feasibility of deployment of SES in AIS. The use
      of these devices yielded higher recanalization rates compared to traditional
      thrombectomy devices. Encouraged by these results, retrievable SES systems have
      been recently used in AIS. These devices offer the advantage of resheathing and
      retrieving of the stent even after full deployment. Some of these stents can also
      be detached in case permanent stent placement is needed. Retrievable SES are
      being used in Europe and currently tested in clinical trials in the United
      States. We review the recent literature in the use of stents for the treatment of
      AIS secondary to large vessel occlusion.

PMID- 22163226
TI  - Genome-Wide Sequence Variation among Mycobacterium avium Subspecies
      paratuberculosis Isolates: A Better Understanding of Johne's Disease Transmission
      Dynamics.
AB  - Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of
      Johne's disease, infects many farmed ruminants, wild-life animals, and recently
      isolated from humans. To better understand the molecular pathogenesis of these
      infections, we analyzed the whole-genome sequences of several M. ap and M. avium
      subspecies avium (M. avium) isolates to gain insights into genomic diversity
      associated with variable hosts and environments. Using Next-generation sequencing
      technology, all six M. ap isolates showed a high percentage of similarity (98%)
      to the reference genome sequence of M. ap K-10 isolated from cattle. However, two
      M. avium isolates (DT 78 and Env 77) showed significant sequence diversity (only
      87 and 40% similarity, respectively) compared to the reference strain M. avium
      104, a reflection of the wide environmental niches of this group of mycobacteria.
      Within the M. ap isolates, genomic rearrangements (insertions/deletions) were not
      detected, and only unique single nucleotide polymorphisms (SNPs) were observed
      among M. ap isolates. While more of the SNPs (~100) in M. ap genomes were non
      synonymous, a total of ~6,000 SNPs were detected among M. avium genomes, most of
      them were synonymous suggesting a differential selective pressure between M. ap
      and M. avium isolates. In addition, SNPs-based phylo-genomics had a enough
      discriminatory power to differentiate between isolates from different hosts but
      yet suggesting a bovine source of infection to other animals examined in this
      study. Interestingly, the human isolate (M. ap 4B) was closely related to a M. ap
      isolate from a dairy facility, suggesting a common source of infection. Overall,
      the identified phylo-genomes further supported the idea of a common ancestor to
      both M. ap and M. avium isolates. Genome-wide analysis described here could
      provide a strong foundation for a population genetic structure that could be
      useful for the analysis of mycobacterial evolution and for the tracking of
      Johne's disease transmission among animals.

PMID- 22163227
TI  - Morphogenesis of the Infectious HIV-1 Virion.
AB  - The virion of HIV-1 is spherical and viral glycoprotein spikes (gp120, gp41)
      protrude from its envelope. The characteristic cone-shaped core exists within the
      virion, caging the ribonucleoprotein (RNP) complex, which is comprised of viral
      RNA, nucleocapsid (NC), and viral enzymes. The HIV-1 virion is budded and
      released from the infected cell as an immature donut-shaped particle. During or
      immediately after release, viral protease (PR) is activated and subsequently
      processes the viral structural protein Gag. Through this maturation process,
      virions acquire infectivity, but its mechanism and transition of morphology
      largely remain unclear. Recent technological advances in experimental devices and
      techniques have made it possible to closely dissect the viral production site on
      the cell, the exterior - or even the interior - of an individual virion, and many
      new aspects on virion morphology and maturation. In this manuscript, I review the
      morphogenesis of HIV-1 virions. I focus on several studies, including some of our
      recent findings, which examined virion formation and/or maturation processes. The
      story of novel compound, which inhibits virion maturation, and the importance of
      maturation research are also discussed.

PMID- 22163228
TI  - Factors associated with cognitive decline in elderly diabetics.
AB  - BACKGROUND/AIMS: Although recent evidence has indicated that type 2 diabetes
      mellitus (T2DM) in the elderly is a risk factor for cognitive dysfunction or
      dementia, few studies have prospectively observed this potential cognitive
      decline. In the current study, we performed cognitive assessments at baseline and
      after 3 years in the same patient group in an attempt to reveal the contributions
      of diabetes-related factors to the increased decline in cognitive function in
      elderly patients with T2DM. METHODS: We recruited 55 consecutive T2DM patients
      with a Mini-Mental State Examination (MMSE) score >=24 from the Diabetic Center
      at the Chubu Rosai Hospital. These patients ranged in age from 65 to 85 years.
      Cognitive and clinical assessments, including brain MRI, were performed at
      baseline and at the 3-year follow-up. RESULTS: The higher plasma insulin and
      HbA(1c) levels observed at baseline were significantly associated with a worse
      cognitive performance at baseline and a more neurocognitive decline at the follow
      up visit. CONCLUSION: The current prospective study suggests that higher insulin
      and glycohemoglobin levels may be associated with diabetes-related cognitive
      dysfunction.

PMID- 22163229
TI  - An open-label, multicenter observational study for patients with Alzheimer's
      disease treated with memantine in the clinical practice.
AB  - BACKGROUND/AIMS: In this post-marketing observational study, the safety and
      effectiveness of memantine were evaluated in patients with Alzheimer's disease
      (AD). METHODS: In a 6-month, observational, open-label study at 202 specialist
      sites in Greece, the effectiveness of memantine was evaluated using the Mini
      Mental State Examination (MMSE) and the Instrumental Activities of Daily Living
      (IADL) scale at baseline, and after 3 and 6 months. Discontinuation rates and
      adverse drug reactions (ADRs) were also recorded to evaluate the safety profile
      of memantine. RESULTS: 2,570 patients participated in the study. Three and 6
      months after baseline, MMSE and IADL scores were significantly improved compared
      to baseline. At the end of the study, 67% of the patients had improved their MMSE
      score; 7.1% of the patients reported >=1 ADRs, and treatment was discontinued due
      to ADR in 0.7%. CONCLUSION: Memantine was well tolerated and had a positive
      effect on the patient's cognitive and functional ability in real-life clinical
      practice, in agreement with randomized, controlled trials.

PMID- 22163230
TI  - Different characteristics of cognitive impairment in elderly schizophrenia and
      Alzheimer's disease in the mild cognitive impairment stage.
AB  - We compared indices of the revised version of the Wechsler Memory Scale (WMS-R)
      and scaled scores of the five subtests of the revised version of the Wechsler
      Adult Intelligence Scale (WAIS-R) in 30 elderly schizophrenia (ES) patients and
      25 Alzheimer's disease (AD) patients in the amnestic mild cognitive impairment
      (aMCI) stage (AD-aMCI). In the WMS-R, attention/concentration was rated lower and
      delayed recall was rated higher in ES than in AD-aMCI, although general memory
      was comparable in the two groups. In WAIS-R, digit symbol substitution,
      similarity, picture completion, and block design scores were significantly lower
      in ES than in AD-aMCI, but the information scores were comparable between the two
      groups. Delayed recall and forgetfulness were less impaired, and attention,
      working memory and executive function were more impaired in ES than in AD-aMCI.
      These results should help clinicians to distinguish ES combined with AD-aMCI from
      ES alone.

PMID- 22163231
TI  - Screening for new biomarkers for subcortical vascular dementia and Alzheimer's
      disease.
AB  - BACKGROUND: Novel biomarkers are important for identifying as well as
      differentiating subcortical vascular dementia (SVD) and Alzheimer's disease (AD)
      at an early stage in the disease process. METHODS: In two independent cohorts, a
      multiplex immunoassay was utilized to analyze 90 proteins in cerebrospinal fluid
      (CSF) samples from dementia patients and patients at risk of developing dementia
      (mild cognitive impairment). RESULTS: The levels of several CSF proteins were
      increased in SVD and its incipient state, and in moderate-to-severe AD compared
      with the control group. In contrast, some CSF proteins were altered in AD, but
      not in SVD. The levels of heart-type fatty acid binding protein (H-FABP) were
      consistently increased in all groups with dementia but only in some of their
      incipient states. CONCLUSIONS: In summary, these results support the notion that
      SVD and AD are driven by different pathophysiological mechanisms reflected in the
      CSF protein profile and that H-FABP in CSF is a general marker of
      neurodegeneration.

PMID- 22163232
TI  - Anticholinergic drugs and their effects on delirium and mortality in the elderly.
AB  - AIM: To investigate the use of drugs with anticholinergic properties (DAPs) and
      their associations with delirium and mortality among elderly patients with
      comorbidities. METHODS: 425 patients (>=70 years of age) in geriatric wards and
      nursing homes were assessed. The use of DAPs was retrieved from their medical
      records. Delirium was diagnosed according to the DSM-IV criteria. RESULTS: Of the
      341 patients (80.2%) treated with multiple DAPs (>=2), 92 patients (27.0%)
      suffered from delirium, whereas 14 of 84 patients (16.7%) without DAP treatment
      had delirium (p = 0.050). In a logistic regression analysis with age, gender, and
      Charlson Comorbidity Index as covariates, DAP treatment did not predict delirium
      (odds ratio 1.67, 95% confidence interval 0.87-3.21). The 2-year mortality was
      49.3% (n = 168) in DAP users and 35.7% (n = 30) in non-users, respectively (p =
      0.026). In the Cox proportional hazard model adjusted for age, gender, and
      comorbidity, DAPs did not predict mortality (hazard ratio 1.12, 95% confidence
      interval 0.75-1.68). CONCLUSION: The use of DAPs is very frequent among frail
      inpatients with comorbidities, but their use has no independent prognostic
      significance.

PMID- 22163233
TI  - Impairment in proverb interpretation as an executive function deficit in patients
      with amnestic mild cognitive impairment and early Alzheimer's disease.
AB  - BACKGROUND/AIMS: Proverb interpretation is assumed to reflect executive
      functions. We hypothesized that proverb interpretation is impaired in patients
      with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain
      impairment by common neuropsychological testing. METHODS: We compared performance
      in a proverb interpretation test in single-domain aMCI patients and patients with
      early Alzheimer's disease (EAD). RESULTS: The groups with aMCI and EAD performed
      significantly worse than healthy controls. Both patient groups gave concrete
      answers with a similar frequency. However, patients with EAD tended to give
      senseless answers more frequently. CONCLUSIONS: Our data suggest that in patients
      diagnosed as single-domain aMCI, deterioration of executive functions is
      detectable with subtle and appropriate neuropsychological testing. Implementation
      of these procedures may improve the early prediction of AD.

PMID- 22163234
TI  - A Longitudinal SPECT Study of Different Patterns of Regional Cerebral Blood Flow
      in Alzheimer's Disease with or without Diabetes.
AB  - AIMS: To determine the effect of diabetes mellitus (DM) on regional cerebral
      blood flow (rCBF) patterns in patients with Alzheimer's disease (AD). METHODS: We
      investigated the initial rCBF of 71 AD patients (36 without DM and 35 with DM)
      and the final rCBF of 23 AD patients (12 without DM and 11 with DM) after an
      average of 32 months. Single-photon emission computed tomography (SPECT) data
      were analyzed by statistical brain imaging. RESULTS: The initial SPECT showed
      that AD patients without DM had lower rCBF in the left and right inferior
      temporal gyri than AD patients with DM. A follow-up SPECT demonstrated that rCBF
      decreased in more widespread regions, including the parietal, temporal, frontal,
      and limbic lobes, in AD patients without than with DM. CONCLUSION: This study
      suggests that functional brain abnormalities in AD differ depending on the DM
      status at baseline and during follow-up, reflecting neuropathologic differences.

PMID- 22163235
TI  - Longitudinal assessment of cognitive function by clock drawing in older adults.
AB  - AIMS: To test the hypotheses that performance on a clock-drawing task (CDT)
      diminishes over time and that poor performance is associated with development of
      dementia and reduced survival. METHODS: Participants in the population-based
      Leisure World Cohort Study were asked to complete a CDT in follow-up
      questionnaires mailed in 1992 and 1998. Dementia status was determined using in
      person evaluations, follow-up questionnaires, hospital data, and death
      certificates. RESULTS: Of the 4,842 cohort members (mean age 80 years) who
      completed the CDT in 1992, 1,521 also completed it in 1998. Although performance
      in the CDT diminished over time in only a proportion of the cohort, the mean
      total score and the percentage of subjects with correctly drawn clocks decreased
      with each successive 5-year age group (p = 0.0001) and over time. Mean scores
      were lower in non-demented subjects later identified as demented compared with
      those who remained free of dementia. A low CDT score in 1992 was associated with
      a 28% increased risk of dementia and 13% reduced survival. CONCLUSION: A CDT may
      help predict cognitive decline and future disability in the elderly.
      Identification of high-risk individuals using a CDT may lead to earlier diagnosis
      and treatment and improved patient management.

PMID- 22163236
TI  - Proactive approach in detecting elderly subjects with cognitive decline in
      general practitioners' practices.
AB  - BACKGROUND: Although cognitive decline is a common finding among the elderly and
      is considered a risk factor for developing dementia, it is rarely diagnosed by
      general practitioners (GPs). AIM: To evaluate cognitive function with the Mini
      Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in
      asymptomatic subjects in daily GP practice and compare subjects who confirmed
      having cognitive problems with subjects who did not. METHODS: 388 consecutive
      subjects >65 years of age who consulted their GP were interviewed and tested with
      MMSE and MoCA. RESULTS: None of the study subjects spontaneously complained of
      cognitive or memory problems. 155 subjects (39.94%) confirmed having cognitive
      problems and 233 (60.05%) did not even when asked. The prevalence of mild
      cognitive impairment (MCI) was 18.30% (95% CI 14.36-22.04) and the prevalence of
      cognitive impairment/no dementia (CIND) was 17.27% (95% CI 13.50-21.04). Delayed
      memory recall as a separate cognitive domain in MoCA was significantly worse in
      subjects with MCI (p = 0.00958) and in those with CIND (p = 0.0208). CONCLUSION:
      There is a significant number of patients in daily GP practices with
      unrecognized, but objectively verifiable, cognitive deficits who do not report
      having cognitive problems. They can be identified by assessment with MMSE and
      MoCA already in the GP practice.

PMID- 22163237
TI  - Midlife healthy-diet index and late-life dementia and Alzheimer's disease.
AB  - AIM: To study long-term effects of dietary patterns on dementia and Alzheimer's
      disease (AD). METHODS: Of 525 subjects randomly selected from population-based
      cohorts surveyed at midlife, a total of 385 (73%) subjects were re-examined 14
      years later in the CAIDE study. A healthy-diet index (range 0-17) was constructed
      including both healthy and unhealthy dietary components. RESULTS: Persons with a
      healthy diet (healthy-diet index >8 points) had a decreased risk of dementia (OR
      0.12, 95% CI 0.02-0.85) and AD (OR 0.08, 95% CI 0.01-0.89) compared with persons
      with an unhealthy diet (0-8 points), adjusting for several possible confounders.
      CONCLUSIONS: Healthy diet at midlife is associated with a decreased risk of
      dementia/AD in late life. These findings highlight the importance of dietary
      patterns and may make more effective measures for dementia/AD prevention or
      postponement possible.

PMID- 22163238
TI  - Amnestic mild cognitive impairment and early Alzheimer's disease in an asian
      memory clinic - evidence for a clinical spectrum.
AB  - OBJECTIVES: To determine if mild cognitive impairment (MCI) represents a
      continuum of cognitive and functional deficits. METHODS: Clinical data of 164
      subjects with no dementia (ND, n = 52), uncertain dementia (n = 69), and mild
      probable Alzheimer's disease (AD, n = 43) were reviewed. Uncertain dementia
      patients were classified as pre-MCI (n = 11), early amnestic MCI (e-aMCI, n = 15)
      and late amnestic MCI (l-aMCI, n = 15). Cognitive assessments [Chinese Mini
      Mental State Examination (CMMSE) and a validated neuropsychological battery],
      functional assessments (Lawton's scale for instrumental activities of daily
      living) and neuroimaging (ischemic lesions and medial temporal lobe atrophy) were
      reviewed. RESULTS: ND, aMCI and mild AD subjects demonstrated a significant trend
      for worsening performance for all cognitive and functional measures (ANOVA, p <
      0.05). Pre-MCI subjects performed significantly better than aMCI subjects in all
      verbal memory domains (p < 0.001), while l-aMCI had worse functional performance
      (p = 0.007), a trend towards greater depressive symptoms (p = 0.05) and higher
      medial temporal lobe atrophy scores (p = 0.06). l-aMCI subjects were more likely
      than either pre-MCI or e-aMCI to progress to dementia over a mean follow-up
      period of 2.5 years (46.7 vs. 9.1 and 20.0%, respectively). CONCLUSIONS: Clinical
      delineation of aMCI allows the differentiation of those likely to progress for
      better correlation to biomarker development.

PMID- 22163239
TI  - Emotional working memory in Alzheimer's disease patients.
AB  - BACKGROUND: Few studies have assessed whether emotional content affects processes
      supporting working memory in Alzheimer disease (AD) patients. METHODS: We
      assessed 22 AD patients and 40 elderly controls (EC) with a delayed matching and
      non-matching to sample task (DMST/DNMST), and a spatial-delayed recognition span
      task (SRST; unique/varied) using emotional stimuli. RESULTS: AD patients showed
      decreased performance on both tasks compared with EC. With regard to the valence
      of the stimuli, we did not observe significant performance differences between
      groups in the DMST/DNMST. However, both groups remembered a larger number of
      negative than positive or neutral pictures on unique SRST. CONCLUSION: The
      results suggest that AD patients show a relative preservation of working memory
      for emotional information, particularly for negative stimuli.

PMID- 22163240
TI  - Does the Use of Nursing-Care Services Reduce the Information about Dementia
      Patients Provided by Their Caregivers?
AB  - BACKGROUND: The rate of use of nursing-care services has been increasing
      dramatically in recent years with the upgrading of the public long-term care
      insurance system in Japan. We addressed how the increased use of the nursing-care
      services might affect the information on the patients provided by their
      caregivers. METHODS: A questionnaire survey of 531 family caregivers caring for
      dementia patients at home was carried out to investigate how the use of these
      services might affect the information about the patients provided by the
      caregivers. The survey revealed that the use of the nursing-care services reduced
      the burden (quality, quantity, time of nursing care, and feeling) on the
      caregivers. RESULTS: According to the observation provided by the caregivers, the
      patients' behaviors and activities at home tended to decrease. These results
      indicated that the use of the nursing-care services resulted in a reduction in
      the opportunity for and the time spent on observation of the patients by the
      caregivers, making it more difficult for the caregiver to provide an appropriate
      assessment of the patient's condition. CONCLUSIONS: We discussed the impact of
      the use of the nursing-care services on the Clinician's Interview-Based
      Impression of Change plus (CIBIC-plus) rating. Due to the reduction in the time
      spent on nursing care and in the opportunity for observation of the patient's
      activities of daily living by the caregiver resulting from the use of the nursing
      care services, it is difficult to obtain an accurate picture of the patient's
      clinical condition using the CIBIC-plus, probably leading to an inappropriate
      CIBIC-plus rating.

PMID- 22163241
TI  - The effect of vascular risk factors on the efficacy of rivastigmine patch and
      capsule treatment in Alzheimer's disease.
AB  - BACKGROUND: Vascular risk factors (VRF) may influence response to rivastigmine in
      Alzheimer's disease (AD). METHODS: AD patients who participated in a randomized,
      double-blind, placebo-controlled trial of rivastigmine patch and capsule
      treatment were stratified by baseline VRF status. Treatment response was
      evaluated using the AD Assessment Scale-cognitive subscale (ADAS-cog), AD
      Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) and the AD
      Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. RESULTS: ADAS-cog
      scores significantly improved in all rivastigmine-treated patients (p < 0.05 vs.
      placebo), except 9.5 mg/24 h patch-treated patients with VRF, and were
      significantly affected by VRF status in the study population as a whole.
      Significant benefits were seen on the ADCS-ADL in 9.5 mg/24 h patch- and capsule
      treated patients with, but not without, VRF. The ADCS-CGIC significantly improved
      in capsule-treated patients with, and patch-treated patients without VRF.
      Although non-significant, patients without VRF showed an apparent faster rate of
      placebo decline. CONCLUSION: VRF may influence AD progression and response to
      rivastigmine.

PMID- 22163242
TI  - A 24-week, randomized, double-blind, placebo-controlled study to evaluate the
      efficacy, safety and tolerability of the rivastigmine patch in Japanese patients
      with Alzheimer's disease.
AB  - BACKGROUND: As of 2010, the rivastigmine patch was licensed for the treatment of
      Alzheimer's disease (AD) in 64 countries. METHODS: This 24-week, multicenter,
      randomized, double-blind, placebo-controlled study evaluated the efficacy, safety
      and tolerability of the 5-cm(2) (9-mg loading dose; 4.6 mg/24 h delivery rate)
      and 10-cm(2) (18-mg loading dose; 9.5 mg/24 h delivery rate) rivastigmine patch
      in Japanese patients with AD. RESULTS: In the primary analysis population (intent
      to-treat last observation carried forward) at week 24, delayed deterioration was
      seen with the 10-cm(2) patch versus placebo on the Japanese version of the
      Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-J cog; p = 0.005)
      and the Japanese version of the Clinician's Interview-Based Impression of Change
      plus Caregiver Input (CIBIC plus-J; p = 0.067). Participants receiving the
      rivastigmine patch showed numerically less decline versus placebo at week 24 on
      the CIBIC plus-J, although this did not reach statistical significance.
      Statistical significance for the CIBIC plus-J was met following adjustment for
      body weight and baseline Mini-Mental State Examination score as dynamic
      allocation factors (p = 0.042) and on the Disability Assessment for Dementia
      (DAD; p = 0.024) and Mental Function Impairment (MENFIS; p = 0.016) subscales.
      Serious adverse events were rare and were consistent with the known safety
      profile of the rivastigmine patch. CONCLUSION: The rivastigmine patch has a
      favorable efficacy and tolerability profile in Japanese patients with AD.

PMID- 22163243
TI  - Pharmacogenetic Study on the Effect of Rivastigmine on PS2 and APOE Genes in
      Iranian Alzheimer Patients.
AB  - BACKGROUND/AIMS: Alzheimer disease (AD) is a complex and genetically
      heterogeneous disorder, and certain genes such as PS2 and APOE4 contribute to the
      development of AD. Due to its heterogeneity, AD-predisposing genes could vary in
      different populations. Moreover, not all AD patients will respond to the same
      therapy. We specifically investigated the effect ofrivastigmine (Exelon) on PS2
      and APOE genes in Iranian AD patients. METHODS: A total of 100 AD patients, 67
      patients with sporadic AD (SAD) and 33 patients with familial AD (FAD), receiving
      rivastigmine therapy and 100 healthy controls were studied. PCR-RFLP was used for
      genotyping of PS2 and APOE. RESULTS: We found a positive association between the
      PS2 -A allele and SAD patients (p(c) = 0.01), and the PS2 +A/-A genotype was
      significantly more frequent in SAD than FAD patients (p(c) = 0.009). The APOE4
      allele was associated with total AD, SAD and FAD (p(c) = 0.000002). Patients with
      the PS2 +A/-A genotype and bigenic genotypes of +A/-A.?3/?3 and +A/-A.?3/?4 were
      the best responders to Exelon therapy, and those with the PS2 +A/+A and APOE
      ?3/?4 genotypes were the worst responders. CONCLUSION: Our findings suggest that
      the PS2 and APOE4 alleles and genotypes affect both AD risk and response to
      rivastigmine therapy.

PMID- 22163244
TI  - Neural Correlates of Stroop Performance in Alzheimer's Disease: A FDG-PET Study.
AB  - BACKGROUND/AIMS: The Stroop test is commonly applied in elderly subjects for the
      evaluation of cognitive impairment related to Alzheimer's disease (AD) and
      related disorders. This study aimed to investigate the functional neural
      correlates of the Stroop performance in AD. METHODS: In 136 probable AD patients
      and 54 cognitively normal elderly, a [(18)F]-fluorodeoxyglucose positron emission
      tomography scan and Stroop Color Word Test (SCWT) were performed. The
      correlations between the Stroop effect, which was measured by 6 different scoring
      methods, and regional cerebral glucose metabolism (rCMglc) were explored using a
      region-of-interest (ROI) approach and voxel-based analysis. RESULTS: Among 6
      Stroop interference measures, only 2 scores, including the SCWT color-word (CW)
      score, were significantly correlated with rCMglc of the dorsolateral prefrontal
      and anterior cingulate ROIs. Voxel-based analysis revealed significant positive
      correlations between SCWT CW scores and rCMglc in the inferior parietal lobule,
      middle temporal gyrus and middle frontal gyrus. Such correlations remained
      significant only in the less severe AD group. CONCLUSION: In AD patients, the
      Stroop effect depends on the functional integrity of the prefrontal cortices.
      Some parietotemporal regions also appear to be responsible for the Stroop effect
      in AD individuals.

PMID- 22163245
TI  - Cognitive profile of idiopathic normal pressure hydrocephalus.
AB  - BACKGROUND/AIMS: Frontal lobe dysfunction is believed to be a primary cognitive
      symptom in idiopathic normal pressure hydrocephalus (iNPH); however, the
      neuropsychology of this disorder remains to be fully investigated. The objective
      of this study was to delineate a comprehensive profile of cognitive dysfunction
      in iNPH and evaluate the effects of cerebrospinal fluid (CSF) shunt surgery on
      cognitive dysfunction. METHODS: A total of 32 iNPH patients underwent
      neuropsychological testing of memory, attention, language, executive function,
      and visuoperceptual and visuospatial abilities. Of these 32 patients, 26 were
      reevaluated approximately 1 year following CSF shunt surgery. The same battery of
      tests was performed on 32 patients with Alzheimer's disease (AD) and 30 healthy
      elderly controls. RESULTS: The iNPH patients displayed baseline deficits in
      attention, executive function, memory, and visuoperceptual and visuospatial
      functions. Impairments of attention, executive function, and visuoperceptual and
      visuospatial abilities in iNPH patients were more severe than in those with AD,
      whereas the degree of memory impairment was comparable to that in AD patients. A
      significant improvement in executive function was observed following shunt
      surgery. CONCLUSION: Patients with iNPH are impaired in various aspects of
      cognition involving both 'frontal' executive functions and 'posterior cortical'
      functions. Shunt treatment can ameliorate executive dysfunction.

PMID- 22163246
TI  - The efficacy of licensed-indication use of donepezil and memantine monotherapies
      for treating behavioural and psychological symptoms of dementia in patients with
      Alzheimer's disease: systematic review and meta-analysis.
AB  - BACKGROUND/AIMS: Behavioural and psychological symptoms of dementia (BPSD) in
      Alzheimer's disease (AD) greatly increase caregiver burden. The abilities of
      donepezil and memantine to manage BPSD within their licensed indications in AD
      were compared. METHODS: A systematic review, random effects meta-analysis and
      Bucher indirect comparison were conducted. RESULTS: Six randomised controlled
      studies (4 donepezil and 2 memantine) reported use within the licensed indication
      and had Neuropsychiatric Inventory (NPI) data suitable for meta-analysis. BPSD
      showed significant improvement with donepezil compared with placebo [weighted
      mean difference (WMD) in NPI -3.51, 95% confidence interval (CI) -5.75, -1.27],
      whereas this was not the case for memantine (WMD -1.65, 95% CI -4.78, 1.49). WMD
      in NPI for donepezil versus memantine favoured donepezil but was not
      statistically significant (-1.86, 95% CI -5.71, 1.99; p = 0.34). CONCLUSION:
      Within its licensed indication, donepezil is efficacious for the management of
      BPSD in AD compared with placebo.

PMID- 22163247
TI  - Asymmetric cerebral blood flow in patients with mild cognitive impairment:
      possible relationship to further cognitive deterioration.
AB  - AIM: To explore patterns of cerebral blood flow in patients with mild cognitive
      impairment (MCI), who (1) eventually deteriorate into overt dementia, with no
      particular focus on the type of dementia, or (2) do not appear to further
      deteriorate in their cognitive functions. METHODS: Thirty-seven MCI patients,
      with or without vascular pathology, were studied prospectively. The patients
      underwent (99m)Tc-HMPAO SPECT analysis at baseline. Possible clinical conversion
      into dementia within a 2-year period was assessed. RESULTS: Nineteen patients had
      progressive MCI (PMCI), while 18 patients were considered clinically stable
      (SMCI). PMCI patients had more often abnormally low cerebral blood flow in at
      least one of the frontal, temporal, parietal or occipital lobes compared to SMCI
      patients (12/19 vs. 5/18; p = 0.049). At least one of the temporal regions was
      found to be abnormal in 9 PMCI patients in contrast to only 1 SMCI patient (p =
      0.008). More specifically, blood flow in the medial portion of the left temporal
      region was abnormal in 8 PMCI patients, a pattern seen in 1 SMCI patient only (p
      = 0.019). CONCLUSION: The results suggest that blood flow reductions particularly
      in the left medial temporal region indicate an elevated risk of further cognitive
      decline in MCI patients.

PMID- 22163248
TI  - Onset Patterns and Initial Symptoms of Dementia with Lewy Bodies: Possible
      Pathophysiological Diversities Deduced from a SPECT Study.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate onset patterns and
      initial symptoms in patients with dementia with Lewy bodies (DLB) and their
      association with SPECT findings. METHODS: We studied 29 probable and 12 possible
      DLB patients. Onset was defined as 'acute' when symptoms (in various
      combinations) present within a few weeks or 'chronic' when a few symptoms present
      and progress during a longer period of time. Initial symptoms were dichotomized
      into 'cognitive' and 'non-cognitive'. We conducted voxel-to-voxel statistical
      analyses of SPECT, and uptake deviations from age-matched controls were depicted
      with Z-scores. RESULTS: In acute patients, decreases were more apparent in the
      bilateral frontal and temporal lobes, whereas chronic patients showed decreases
      in the bilateral occipital, posterior cingulate and precuneal regions.
      Differences in the left frontal and left posterior cingulate were significant and
      those in the left temporal region showed a tendency toward significance. Patients
      with cognitive symptoms demonstrated more marked decreases in the bilateral
      temporal, parietal, occipital, cingulate and precuneal regions. Differences in
      the left parietal area reached significance and the total decreases were larger
      in patients with cognitive than non-cognitive symptoms, with a trend toward
      significance. CONCLUSIONS: The multiplicity of onset patterns and initial
      symptoms may possibly be based on pathophysiological diversities in DLB.

PMID- 22163249
TI  - Performance on the RI-48 Cued Recall Test Best Predicts Conversion to Dementia at
      the 5- and 10-Year Follow-Ups.
AB  - BACKGROUND: TheRI-48 cued recall test was devised to discriminate between healthy
      elderly and patients with mild cognitive impairment who are at risk of developing
      Alzheimer's disease (AD). However, no long-term follow-up studies have been
      conducted using this test. METHODS: We analyzed the predictive power of the RI-48
      test for determining the patients who will convert to AD dementia within the
      decade after testing. During 10 years, we followed up 40 non-demented patients
      who attended our Memory Clinic and underwent complete neuropsychological
      evaluation including the RI-48. RESULTS: Of the 40 patients, 21 developed
      dementia (converters, CO) and 19 remained stable patients (SP). Of the tests
      performed at inclusion, only the RI-48 (p < 0.0001) and semantic fluency (p =
      0.030) tests gave significantly different results between CO and SP. CONCLUSION:
      The RI-48 had the best overall diagnostic accuracy at 5- and at 10-year follow
      ups.

PMID- 22163250
TI  - Mild cognitive impairment and dementia: the importance of modifiable risk
      factors.
AB  - BACKGROUND: Mild cognitive impairment (MCI), a common condition among the
      elderly, is defined as a deterioration of memory, attention, and cognitive
      function that exceeds what would be expected for the individual's age and level
      of education, yet does not interfere significantly with the activities of daily
      living. MCI may be a precursor of dementia; the rate of transition from MCI to
      dementia is 10% to 20% per year. The role of somatic diseases and modifiable risk
      factors in MCI and dementia needs further study. METHODS: We analyzed pertinent
      original articles and reviews published 1990 up to December 2010 that were
      retrieved by a selective search in PubMed and the Cochrane Library. RESULTS: MCI
      and dementia are associated with many somatic disorders and modifiable risk
      factors. MCI has biologically plausible associations with hypertension, diabetes
      mellitus, and hyperlipidemia, although the interventional trials performed to
      date have yielded negative results. Recently, chronic renal failure has also been
      recognized as a risk factor. Insufficient evidence supports a putative benefit on
      MCI from the substitution of vitamin B12, vitamin D, or testosterone (when these
      substances are deficient), the treatment of hyperhomocysteinemia or subclinical
      thyroid dysfunction, or hormone replacement therapy after menopause.
      Epidemiological data suggest that a Mediterranean diet, physical activity, and
      moderate alcohol consumption protect against MCI, while cigarette smoking
      promotes it and should be stopped. CONCLUSION: Modifiable risk factors for MCI
      should be sought (at the very latest) in persons who already have MCI, as their
      optimal treatment may improve these patients' cognitive performance or keep the
      existing deficits from progressing.

PMID- 22163251
TI  - Irritable bowel syndrome--the main recommendations.
AB  - BACKGROUND: Irritable bowel syndrome is characterized by chronic abdominal
      symptoms and irregular bowel movements without any cause than can be revealed by
      routine diagnostic assessment. In recent years, its pathophysiology has come to
      be much better understood, and new therapeutic approaches have been developed.
      These advances were taken into consideration and assessed for their relevance to
      clinical practice in the framework of a new interdisciplinary S3 guideline.
      METHODS: A systematic search of the literature retrieved a total 5573 articles,
      from which 243 were selected on the basis of criteria relating to their form and
      content, individually assessed, and summarized in evidence tables. The
      recommendations formulated in this way were discussed in a Delphi procedure and a
      consensus conference, then accordingly modified and finalized. RESULTS: Variable
      symptom constellations are caused by disturbances of gastrointestinal regulation
      at multiple levels. The diagnosis of irritable bowel syndrome requires both
      chronic bowel symptoms that interfere with everyday life and the exclusion of
      relevant differential diagnoses. Its treatment is based on general therapeutic
      principles, dietary recommendations, psychological components, and symptomatic
      medication. Bulking agents, laxatives, spasmolytics, loperamide, and probiotic
      agents are recommended (with variable recommendation strengths), as are--for
      selected patients--antidepressants, 5-HT4 agonists, 5-HT3 antagonists, and
      topical antibiotics. CONCLUSION: The first German S3 guideline on irritable bowel
      syndrome translates up-to-date scientific knowledge as represented in current
      publications into concrete recommendations for diagnosis and treatment in
      clinical practice. In the future, it is likely that further causative
      pathophysiological mechanisms will be discovered; this should lead, in turn, to
      the development of new, causally directed treatments, which will supplement or
      replace the traditional, purely symptomatic treatments that are still in use
      today.

PMID- 22163253
TI  - Correspondence (letter to the editor): Side effects.

PMID- 22163252
TI  - The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in
      Germany.
AB  - BACKGROUND: For decades, methicillin-resistant Staphylococcus aureus (MRSA) has
      been a major cause of infection in hospitals and nursing homes (health care
      associated MRSA, HA-MRSA). Beginning in the late 1990s, many countries have also
      experienced a rising incidence of MRSA infection outside of the health care
      setting (community-associated MRSA, CA-MRSA). Moreover, animal reservoirs are
      increasingly considered to represent an important source of human MRSA
      acquisition. In this review article the authors describe the current
      epidemiological situation of MRSA in Germany. METHODS: This review is based on
      pertinent articles published up to 2010 that were retrieved by a selective PubMed
      search, as well as on publications issued by national reference institutions up
      to 2010. RESULTS: There are about 132 000 cases of MRSA in German hospitals each
      year. MRSA is found in about 18% to 20% of all inpatient-derived culture
      specimens that are positive for S. aureus. CA-MRSA is not yet endemic in Germany;
      important risk factors for its acquisition include travel to high-prevalence
      areas and household contact with persons that harbor a CA-MRSA infection.
      Agricultural livestock is the main animal reservoir for MRSA, which is often
      zoonotically transmitted from animals to human beings by direct contact. However,
      both CA-MRSA and MRSA from animal reservoirs can be imported into hospitals and
      cause nosocomial infections. CONCLUSION: Hospitals and nursing homes were once
      the main reservoirs of MRSA, but new ones have now emerged outside of the
      healthcare setting. Efforts to prevent MRSA and limit its spread must rise to
      this new challenge.

PMID- 22163254
TI  - Correspondence (letter to the editor): Risk of venous thromboembolism.

PMID- 22163255
TI  - Correspondence (letter to the editor): Alternatives.

PMID- 22163256
TI  - Correspondence (letter to the editor): Serious concerns.

PMID- 22163258
TI  - Vaccination recommendations for Germany.
AB  - BACKGROUND: Vaccination is an effective means of preventing infectious diseases.
      In Germany, the Standing Vaccination Committee at the Robert Koch Institute
      (Standige Impfkommission, STIKO) issues recommendations on vaccination to prevent
      the occurrence and spread of infectious diseases in the nation's population.
      METHODS: Selective literature review, including consideration of the current
      STIKO recommendations. RESULTS: The annually updated vaccination calendar
      currently includes recommendations for vaccination against diphtheria, tetanus,
      pertussis, type b Haemophilus influenzae, hepatitis B, poliomyelitis, and
      pneumococci, beginning at the age of eight weeks. From the age of twelve months
      onward, children should be vaccinated against measles, mumps, rubella, varicella,
      and serogroup C meningococci. In later childhood and adolescence, booster
      vaccinations are recommended, in addition to the provision of any vaccinations
      that may have been missed. Girls aged 12 to 17 years should be vaccinated against
      human papilloma virus. Adults should have their tetanus and diphtheria
      vaccinations refreshed regularly, and their pertussis vaccination refreshed once;
      from age 60 onward, they should be vaccinated against pneumococci and influenza.
      CONCLUSIONS: The vaccinations recommended by the STIKO are available to all
      German citizens free of charge and provide effective protection against
      infectious disease.

PMID- 22163259
TI  - Burnout: a fashionable diagnosis.
AB  - BACKGROUND: "Burnout syndrome" is now a common reason for medical excuses from
      work, and thus an important topic in health-related economics. Much research is
      still needed, however, to establish the scientific basis for this entity, the
      criteria by which it might be diagnosed and classified, and how it should be
      treated. METHODS: A systematic review of this topic, previously published as an
      HTA report, is presented here together with a selective overview of pertinent
      literature. RESULTS: There currently exists neither an officially accepted
      definition nor a valid instrument for the differential diagnosis of burnout
      syndrome. Its manifestations are generally considered to lie along three
      dimensions: emotional exhaustion, depersonalization, and reduced performance
      ability and/or motivation. Most of the available studies on its epidemiology and
      differential diagnosis provide no more than a low level of evidence for their
      conclusions. There have been no controlled trials of treatments for burnout.
      CONCLUSION: High-quality controlled studies on burnout syndrome are lacking. A
      standardized and internationally accepted diagnostic instrument with a validated
      rating scale should be developed. There is also a need for epidemiological and
      health-economic studies on the prevalence, incidence, and cost of burnout. The
      etiology and pathogenesis of burnout should be studied with special regard to the
      possible role of neurobiological factors. Treatments for it should be studied
      systematically so that their effects can be judged at a high level of evidence.
      In view of the current lack of knowledge about what is called "burnout," the term
      should not be used as a medical diagnosis or as a basis for decisions regarding
      disability or other socioeconomic matters.

PMID- 22163260
TI  - Intraductal papillary mucinous neoplasia (IPMN) of the pancreas: its diagnosis,
      treatment, and prognosis.
AB  - BACKGROUND: The many varieties of cystic pancreatic tumor, and especially
      intraductal papillary mucinous neoplasia (IPMN), have attracted increased
      attention recently. Their incidence may be rising, and their histopathological
      evaluation and classification have become more precise than before. METHODS: We
      discuss the current diagnostic evaluation of IPMN, along with treatment and
      prognostication, on the basis of the current international guideline as well as
      pertinent literature retrieved by a selective PubMed search. RESULTS: The
      preoperative diagnostic evaluation of IPMN is often problematic. In particular,
      it may not be possible to differentiate main-duct disease from branch-duct
      disease (MD-IPMN vs. BD-IPMN) before surgery--a distinction with implications for
      prognosis and treatment, as MD-IPMN is more often malignant. An IPMN adenoma can
      develop into invasive pancreatic cancer. Because firm diagnostic criteria are
      still lacking, it is recommended that all MD-IPMN lesions and all large BD-IPMN
      lesions should be resected. Partial pancreatectomy with clean margins is the
      treatment of choice. CONCLUSION: As IPMN seems to be a slow-growing precursor of
      pancreatic cancer, it is possible that its early detection and surgical treatment
      can lead to a cure. No conclusion about the efficacy of surveillance and follow
      up programs can be drawn from the available evidence. A better understanding of
      the natural course of IPMN and the biology of pancreatic cancer is needed to
      enable further improvements in diagnosis and treatment.

PMID- 22163261
TI  - Combining textual and visual information for image retrieval in the medical
      domain.
AB  - In this article we have assembled the experience obtained from our participation
      in the imageCLEF evaluation task over the past two years. Exploitation on the use
      of linear combinations for image retrieval has been attempted by combining visual
      and textual sources of images. From our experiments we conclude that a mixed
      retrieval technique that applies both textual and visual retrieval in an
      interchangeably repeated manner improves the performance while overcoming the
      scalability limitations of visual retrieval. In particular, the mean average
      precision (MAP) has increased from 0.01 to 0.15 and 0.087 for 2009 and 2010 data,
      respectively, when content-based image retrieval (CBIR) is performed on the top
      1000 results from textual retrieval based on natural language processing (NLP).

PMID- 22163262
TI  - Neural correlates of cognitive reappraisal in children: an ERP study.
AB  - Cognitive emotion regulation strategies, such as reappraising the emotional
      meaning of events, are linked to positive adjustment and are disrupted in
      individuals showing emotional distress, like anxiety. The late positive potential
      (LPP) is sensitive to reappraisal: LPP amplitudes are reduced when unpleasant
      pictures are reappraised in a positive light, suggesting regulation of negative
      emotion. However, only one study has examined reappraisal in children using the
      LPP. The present study examined whether directed reappraisals reduce the LPP in a
      group of 5- to 7-year-olds, and correlate with individual differences in fear and
      anxiety. EEG was recorded from 32 typically developing children via 64 scalp
      electrodes during a directed reappraisal task. Mothers reported on child anxiety.
      Fearful behavior was observed. As predicted, LPP amplitudes were larger to
      unpleasant versus neutral pictures;counter to predictions, the LPP was not
      sensitive to reappraisal. The degree to which unpleasant versus neutral pictures
      elicited larger LPPs was correlated with greater anxiety and fear. Results
      suggest that reappraisal in young children is still developing, but that the LPP
      is sensitive to individual differences related to fear and anxiety. The utility
      of the LPP as a measure of cognitive emotion regulation and emotional processing
      biases in children is discussed.

PMID- 22163263
TI  - Emotional picture processing in children: an ERP study.
AB  - The late positive potential (LPP) reflects increased attention to emotional
      versus neutral stimuli in adults. To date, very few studies have examined the LPP
      in children, and whether it can be used to measure patterns of emotional
      processing that are related to dispositional mood characteristics, such as
      temperamental fear and anxiety. To examine this question,39 typically developing
      5-7 year olds (M age in months = 75.27, SD = 5.83) passively viewed complex
      emotional and neutral pictures taken from the International Affective Picture
      System.Maternal report of temperamental fear and anxiety was obtained and fearful
      behavior during an emotional challenge was observed. As documented in adults, LPP
      amplitudes to pleasant and unpleasant stimuli were larger than to neutral
      stimuli, although some gender differences emerged. Larger LPP amplitude
      differences between unpleasant and neutral stimuli were associated with greater
      observed fear. The LPP as a measure of individual differences in emotional
      processing is discussed.

PMID- 22163264
TI  - The transient receptor potential ion channel TRPV6 is expressed at low levels in
      osteoblasts and has little role in osteoblast calcium uptake.
AB  - BACKGROUND: TRPV6 ion channels are key mediators of regulated transepithelial
      absorption of Ca2+ within the small intestine. Trpv6-/- mice were reported to
      have lower bone density than wild-type littermates and significant disturbances
      in calcium homeostasis that suggested a role for TRPV6 in osteoblasts during bone
      formation and mineralization. TRPV6 and molecules related to transepithelial Ca2+
      transport have been reported to be expressed at high levels in human and mouse
      osteoblasts. RESULTS: Transmembrane ion currents in whole cell patch clamped SaOS
      2 osteoblasts did not show sensitivity to ruthenium red, an inhibitor of TRPV5/6
      ion channels, and 45Ca uptake was not significantly affected by ruthenium red in
      either SaOS-2 (P=0.77) or TE-85 (P=0.69) osteoblastic cells. In contrast, ion
      currents and 45Ca uptake were both significantly affected in a human bronchial
      epithelial cell line known to express TRPV6. TRPV6 was expressed at lower levels
      in osteoblastic cells than has been reported in some literature. In SaOS-2 TRPV6
      mRNA was below the assay detection limit; in TE-85 TRPV6 mRNA was detected at
      6.90+/-1.9*10(-5) relative to B2M. In contrast, TRPV6 was detected at 7.7+/
      3.0*10(-2) and 2.38+/-0.28*10(-4) the level of B2M in human carcinoma-derived
      cell lines LNCaP and CaCO-2 respectively. In murine primary calvarial osteoblasts
      TRPV6 was detected at 3.80+/-0.24*10(-5) relative to GAPDH, in contrast with
      4.3+/-1.5*10(-2) relative to GAPDH in murine duodenum. By immunohistochemistry,
      TRPV6 was expressed mainly in myleocytic cells of the murine bone marrow and was
      observed only at low levels in murine osteoblasts, osteocytes or growth plate
      cartilage. CONCLUSIONS: TRPV6 is expressed only at low levels in osteoblasts and
      plays little functional role in osteoblastic calcium uptake.

PMID- 22163266
TI  - Temporal patterns of happiness and information in a global social network:
      hedonometrics and Twitter.
AB  - Individual happiness is a fundamental societal metric. Normally measured through
      self-report, happiness has often been indirectly characterized and overshadowed
      by more readily quantifiable economic indicators such as gross domestic product.
      Here, we examine expressions made on the online, global microblog and social
      networking service Twitter, uncovering and explaining temporal variations in
      happiness and information levels over timescales ranging from hours to years. Our
      data set comprises over 46 billion words contained in nearly 4.6 billion
      expressions posted over a 33 month span by over 63 million unique users. In
      measuring happiness, we construct a tunable, real-time, remote-sensing, and non
      invasive, text-based hedonometer. In building our metric, made available with
      this paper, we conducted a survey to obtain happiness evaluations of over 10,000
      individual words, representing a tenfold size improvement over similar existing
      word sets. Rather than being ad hoc, our word list is chosen solely by frequency
      of usage, and we show how a highly robust and tunable metric can be constructed
      and defended.

PMID- 22163265
TI  - Human alveolar epithelial cell injury induced by cigarette smoke.
AB  - BACKGROUND: Cigarette smoke (CS) is a highly complex mixture and many of its
      components are known carcinogens, mutagens, and other toxic substances. CS
      induces oxidative stress and cell death, and this cell toxicity plays a key role
      in the pathogenesis of several pulmonary diseases. METHODOLOGY/PRINCIPAL
      FINDINGS: We studied the effect of cigarette smoke extract (CSE) in human
      alveolar epithelial type I-like (ATI-like) cells. These are isolated type II
      cells that are differentiating toward the type I cell phenotype in vitro and have
      lost many type II cell markers and express type I cell markers. ATI-like cells
      were more sensitive to CSE than alveolar type II cells, which maintained their
      differentiated phenotype in vitro. We observed disruption of mitochondrial
      membrane potential, apoptosis and necrosis that were detected by double staining
      with acridine orange and ethidium bromide or Hoechst 33342 and propidium iodide
      and TUNEL assay after treatment with CSE. We also detected caspase 3 and caspase
      7 activities and lipid peroxidation. CSE induced nuclear translocation of Nrf2
      and increased expression of Nrf2, HO-1, Hsp70 and Fra1. Moreover, we found that
      Nrf2 knockdown sensitized ATI-like cells to CSE and Nrf2 overexpression provided
      protection against CSE-induced cell death. We also observed that two antioxidant
      compounds N-acetylcysteine and trolox protected ATI-like cells against injury by
      CSE. CONCLUSIONS: Our study indicates that Nrf2 activation is a major factor in
      cellular defense of the human alveolar epithelium against CSE-induced toxicity
      and oxidative stress. Therefore, antioxidant agents that modulate Nrf2 would be
      expected to restore antioxidant and detoxifying enzymes and to prevent CS-related
      lung injury and perhaps lessen the development of emphysema.

PMID- 22163267
TI  - The ecology of 'Acroporid white syndrome', a coral disease from the southern
      Great Barrier Reef.
AB  - Outbreaks of coral disease have increased worldwide over the last few decades.
      Despite this, remarkably little is known about the ecology of disease in the Indo
      Pacific Region. Here we report the spatiotemporal dynamics of a coral disease
      termed 'Acroporid white syndrome' observed to affect tabular corals of the genus
      Acropora on the southern Great Barrier Reef. The syndrome is characterised by
      rapid tissue loss initiating in the basal margins of colonies, and manifests as a
      distinct lesion boundary between apparently healthy tissue and exposed white
      skeleton. Surveys of eight sites around Heron Reef in 2004 revealed a mean
      prevalence of 8.1+/-0.9%, affecting the three common species (Acropora cytherea,
      A. hyacinthus, A. clathrata) and nine other tabular Acropora spp. While all sizes
      of colonies were affected, white syndrome disproportionately affected larger
      colonies of tabular Acroporids (>80 cm). The prevalence of white syndrome was
      strongly related to the abundance of tabular Acroporids within transects, yet the
      incidence of the syndrome appears unaffected by proximity to other colonies,
      suggesting that while white syndrome is density dependant, it does not exhibit a
      strongly aggregated spatial pattern consistent with previous coral disease
      outbreaks. Acroporid white syndrome was not transmitted by either direct contact
      in the field or by mucus in aquaria experiments. Monitoring of affected colonies
      revealed highly variable rates of tissue loss ranging from 0 to 1146 cm(-2) week(
      1), amongst the highest documented for a coral disease. Contrary to previous
      links between temperature and coral disease, rates of tissue loss in affected
      colonies increased threefold during the winter months. Given the lack of spatial
      pattern and non-infectious nature of Acroporid white syndrome, further studies
      are needed to determine causal factors and longer-term implications of disease
      outbreaks on the Great Barrier Reef.

PMID- 22163268
TI  - CFTR expression analysis in human nasal epithelial cells by flow cytometry.
AB  - RATIONALE: Unbiased approaches that study aberrant protein expression in primary
      airway epithelial cells at single cell level may profoundly improve diagnosis and
      understanding of airway diseases. We here present a flow cytometric procedure to
      study CFTR expression in human primary nasal epithelial cells from patients with
      Cystic Fibrosis (CF). Our novel approach may be important in monitoring of
      therapeutic responses, and better understanding of CF disease at the molecular
      level. OBJECTIVES: Validation of a panel of CFTR-directed monoclonal antibodies
      for flow cytometry and CFTR expression analysis in nasal epithelial cells from
      healthy controls and CF patients. METHODS: We analyzed CFTR expression in primary
      nasal epithelial cells at single cell level using flow cytometry. Nasal cells
      were stained for pan-Cytokeratin, E cadherin, and CD45 (to discriminate
      epithelial cells and leukocytes) in combination with intracellular staining of
      CFTR. Healthy individuals and CF patients were compared. MEASUREMENTS AND MAIN
      RESULTS: We observed various cellular populations present in nasal brushings that
      expressed CFTR protein at different levels. Our data indicated that CF patients
      homozygous for F508del express varying levels of CFTR protein in nasal epithelial
      cells, although at a lower level than healthy controls. CONCLUSION: CFTR protein
      is expressed in CF patients harboring F508del mutations but at lower levels than
      in healthy controls. Multicolor flow cytometry of nasal cells is a relatively
      simple procedure to analyze the composition of cellular subpopulations and
      protein expression at single cell level.

PMID- 22163270
TI  - The increasing burden of imported chronic hepatitis B--United States, 1974-2008.
AB  - BACKGROUND: Without intervention, up to 25% of individuals chronically infected
      with hepatitis B virus (HBV) die of late complications, including cirrhosis and
      liver cancer. The United States, which in 1991 implemented a strategy to
      eliminate HBV transmission through universal immunization, is a country of low
      prevalence. Approximately 3,000-5,000 U.S.-acquired cases of chronic hepatitis B
      have occurred annually since 2001. Many more chronically infected persons migrate
      to the United States yearly from countries of higher prevalence. Although early
      identification of chronic HBV infection can reduce the likelihood of transmission
      and late complications, immigrants are not routinely screened for HBV infection
      during or after immigration. METHODS: To estimate the number of imported cases of
      chronic hepatitis B, we multiplied country-specific prevalence estimates by the
      yearly number of immigrants from each country during 1974-2008. RESULTS: During
      1974-2008, 27.9 million immigrants entered the U.S. Sixty-three percent were born
      in countries of intermediate or high chronic hepatitis B prevalence (range 2%
      31%). On average, an estimated 53,800 chronic hepatitis B cases were imported to
      the U.S. yearly from 2004 through 2008. The Philippines, China, and Vietnam
      contributed the most imported cases (13.4%, 12.5%, and 11.0%, respectively).
      Imported cases increased from an estimated low of 105,750 during the period 1974
      1977 to a high of 268,800 in 2004-2008. CONCLUSIONS: Imported chronic hepatitis B
      cases account for approximately 95% of new U.S. cases. Earlier case
      identification and management of infected immigrants would strengthen the U.S.
      strategy to eliminate HBV transmission, and could delay disease progression and
      prevent some deaths among new Americans.

PMID- 22163269
TI  - Dietary calcium but not elemental calcium from supplements is associated with
      body composition and obesity in Chinese women.
AB  - OBJECTIVE: We assessed whether dietary calcium intake or calcium supplements
      associated with body composition and obesity in a Chinese population. METHODS: A
      cross-sectional survey was performed in a population of 8940, aged 20 to 74 y.
      8127 participants responded (90.9%). Height, weight, fat mass (FM), waist
      circumference (WC) and hip circumference were measured. Obesity definition: body
      mass index (BMI) >=28 kg/m(2) (overall obesity); WC >=85 cm for men or >=80 cm
      for women (abdominal obesity I) and waist hip ratio (WHR) >=0.90 for men or
      >=0.85 for women (abdominal obesity P). The data on dietary calcium and calcium
      supplements were collected using food-frequency questionnaire and self-report
      questionnaire. Multivariate linear and multivariable logistic regressions were
      used to examine the associations between dietary calcium intake or calcium
      supplements and body composition and obesity. PRINCIPAL FINDINGS: The average
      dietary calcium intake of all subjects was 430 mg/d. After adjusting for
      potential confounding factors, among women only, negative associations were
      observed between habitual dietary calcium intake and four measures of body
      composition (beta, -0.086, P<0.001 for BMI; beta, -0.072, P<0.001 for WC; beta, 
      0.044, P<0.05 for WHR; and beta, -0.058, P<0.01 for FM, respectively) and both
      measures of abdominal obesity (Odds Ratio [OR] = 0.86, 95% Confidence Interval
      [CI], 0.80-0.93; P<0.001, for abdominal obesity I; OR = 0.92, 95% CI, 0.86-0.99;
      P = 0.026, for abdominal obesity II). These associations were not observed among
      men (P>0.05). Similarly, among both men and women, we did not observe significant
      associations between calcium supplements and any measures of body composition or
      abdominal obesity (P>0.05). CONCLUSIONS: Dietary calcium from food rather than
      elemental calcium from calcium supplements has beneficial effects on the
      maintenance of body composition and preventing abdominal obesity in Chinese
      women.

PMID- 22163271
TI  - Phlebotomine fauna (Diptera: Psychodidae) and putative vectors of leishmaniases
      in impacted area by hydroelectric plant, State of Tocantins, Brazil.
AB  - BACKGROUND: Although leishmaniases are regarded as serious public health issues
      in the State of Tocantins, as consequence of the impact of environmental changes,
      small advances in taxonomic and ecological studies of Phlebotominae fauna are
      taking place in this state. The present study aimed to improve the knowledge
      about the sand flies, as well as about the aspects of the bioecology of
      leishmaniases vectors from Porto Nacional, a city that was directly impacted by
      the construction of Luis Eduardo Magalhaes Hydroelectric Plant (HEP-Lajeado).
      METHODOLOGY/PRINCIPAL FINDINGS: Sand flies were collected monthly using CDC light
      traps and Shannon traps for a period of 40 consecutive months, at different
      monitoring stations, where 7162 specimens were collected and 48 species were
      detected. Among the species found, 22 are first records in the state and seven
      are considered important vectors of leishmaniases. Lutzomyia longipalpis, the
      vector of American Visceral Leishmaniasis (AVL) showed higher frequency in urban
      compared to rural areas, and Nyssomyia whitmani, the vector of American Cutaneous
      Leishmaniasis (ACL), predominated in rural areas. The frequency and habits of
      sand fly vectors are discussed considering environmental characteristics and
      climatic factors. CONCLUSIONS/SIGNIFICANCE: The construction of dams requires a
      great amount of labor, therefore attracting people from elsewhere. Increased
      migration, without adequate structure, leads to bad living conditions in new and
      unplanned settlements. It also leads to deforestation associated with
      environmental impacts, which can facilitate the spread of leishmaniases. This
      study discusses the importance of Lu. longipalpis and Ny. whitmani on the
      transmission cycles of leishmaniases in Porto Nacional and the record of Bi.
      flaviscutellata in periurban area of the city.

PMID- 22163272
TI  - Effects of whole-body cryotherapy vs. far-infrared vs. passive modalities on
      recovery from exercise-induced muscle damage in highly-trained runners.
AB  - Enhanced recovery following physical activity and exercise-induced muscle damage
      (EIMD) has become a priority for athletes. Consequently, a number of post
      exercise recovery strategies are used, often without scientific evidence of their
      benefits. Within this framework, the purpose of this study was to test the
      efficacy of whole body cryotherapy (WBC), far infrared (FIR) or passive (PAS)
      modalities in hastening muscular recovery within the 48 hours after a simulated
      trail running race. In 3 non-adjoining weeks, 9 well-trained runners performed 3
      repetitions of a simulated trail run on a motorized treadmill, designed to induce
      muscle damage. Immediately (post), post 24 h, and post 48 h after exercise, all
      participants tested three different recovery modalities (WBC, FIR, PAS) in a
      random order over the three separate weeks. Markers of muscle damage (maximal
      isometric muscle strength, plasma creatine kinase [CK] activity and perceived
      sensations [i.e. pain, tiredness, well-being]) were recorded before, immediately
      after (post), post 1 h, post 24 h, and post 48 h after exercise. In all testing
      sessions, the simulated 48 min trail run induced a similar, significant amount of
      muscle damage. Maximal muscle strength and perceived sensations were recovered
      after the first WBC session (post 1 h), while recovery took 24 h with FIR, and
      was not attained through the PAS recovery modality. No differences in plasma CK
      activity were recorded between conditions. Three WBC sessions performed within
      the 48 hours after a damaging running exercise accelerate recovery from EIMD to a
      greater extent than FIR or PAS modalities.

PMID- 22163273
TI  - Elderly subjects have a delayed antibody response and prolonged viraemia
      following yellow fever vaccination: a prospective controlled cohort study.
AB  - BACKGROUND: Yellow fever vaccination (YF-17D) can cause serious adverse events
      (SAEs). The mechanism of these SAEs is poorly understood. Older age has been
      identified as a risk factor. We tested the hypothesis that the humoral immune
      response to yellow fever vaccine develops more slowly in elderly than in younger
      subjects. METHOD: We vaccinated young volunteers (18-28 yrs, N = 30) and elderly
      travelers (60-81 yrs, N = 28) with YF-17D and measured their neutralizing
      antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5,
      10, 14 and 28 days after vaccination. RESULTS: Ten days after vaccination
      seroprotection was attained by 77% (23/30) of the young participants and by 50%
      (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean
      Titer of younger participants was higher than the GMT of the elderly
      participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8-4.7, p =
      0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1-2.9, p = 0.02, using a mixed linear
      model. Viraemia was more common in the elderly (86%, 24/28) than in the younger
      participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the
      elderly participants. CONCLUSIONS: We found that elderly subjects had a delayed
      antibody response and higher viraemia levels after yellow fever primovaccination.
      We postulate that with older age, a weaker immune response to yellow fever
      vaccine allows the attenuated virus to cause higher viraemia levels which may
      increase the risk of developing SAEs. This may be one piece in the puzzle of the
      pathophysiology of YEL-AVD. TRIAL REGISTRATION: Trialregitser.nl NTR1040.

PMID- 22163274
TI  - Improving the alignment quality of consistency based aligners with an evaluation
      function using synonymous protein words.
AB  - Most sequence alignment tools can successfully align protein sequences with
      higher levels of sequence identity. The accuracy of corresponding structure
      alignment, however, decreases rapidly when considering distantly related
      sequences (<20% identity). In this range of identity, alignments optimized so as
      to maximize sequence similarity are often inaccurate from a structural point of
      view. Over the last two decades, most multiple protein aligners have been
      optimized for their capacity to reproduce structure-based alignments while using
      sequence information. Methods currently available differ essentially in the
      similarity measurement between aligned residues using substitution matrices,
      Fourier transform, sophisticated profile-profile functions, or consistency-based
      approaches, more recently.In this paper, we present a flexible similarity measure
      for residue pairs to improve the quality of protein sequence alignment. Our
      approach, called SymAlign, relies on the identification of conserved words found
      across a sizeable fraction of the considered dataset, and supported by
      evolutionary analysis. These words are then used to define a position specific
      substitution matrix that better reflects the biological significance of local
      similarity. The experiment results show that the SymAlign scoring scheme can be
      incorporated within T-Coffee to improve sequence alignment accuracy. We also
      demonstrate that SymAlign is less sensitive to the presence of structurally non
      similar proteins. In the analysis of the relationship between sequence identity
      and structure similarity, SymAlign can better differentiate structurally similar
      proteins from non- similar proteins. We show that protein sequence alignments can
      be significantly improved using a similarity estimation based on weighted n
      grams. In our analysis of the alignments thus produced, sequence conservation
      becomes a better indicator of structural similarity. SymAlign also provides
      alignment visualization that can display sub-optimal alignments on dot-matrices.
      The visualization makes it easy to identify well-supported alternative alignments
      that may not have been identified by dynamic programming. SymAlign is available
      at http://bio-cluster.iis.sinica.edu.tw/SymAlign/.

PMID- 22163275
TI  - Redistribution of DAT/alpha-synuclein complexes visualized by "in situ" proximity
      ligation assay in transgenic mice modelling early Parkinson's disease.
AB  - Alpha-synuclein, the major component of Lewy bodies, is thought to play a central
      role in the onset of synaptic dysfunctions in Parkinson's disease (PD). In
      particular, alpha-synuclein may affect dopaminergic neuron function as it
      interacts with a key protein modulating dopamine (DA) content at the synapse: the
      DA transporter (DAT). Indeed, recent evidence from our "in vitro" studies showed
      that alpha-synuclein aggregation decreases the expression and membrane
      trafficking of the DAT as the DAT is retained into alpha-synuclein-immunopositive
      inclusions. This notwithstanding, "in vivo" studies on PD animal models
      investigating whether DAT distribution is altered by the pathological
      overexpression and aggregation of alpha-synuclein are missing. By using the
      proximity ligation assay, a technique which allows the "in situ" visualization of
      protein-protein interactions, we studied the occurrence of alterations in the
      distribution of DAT/alpha-synuclein complexes in the SYN120 transgenic mouse
      model, showing insoluble alpha-synuclein aggregates into dopaminergic neurons of
      the nigrostriatal system, reduced striatal DA levels and an altered distribution
      of synaptic proteins in the striatum. We found that DAT/alpha-synuclein complexes
      were markedly redistributed in the striatum and substantia nigra of SYN120 mice.
      These alterations were accompanied by a significant increase of DAT striatal
      levels in transgenic animals when compared to wild type littermates. Our data
      indicate that, in the early pathogenesis of PD, alpha-synuclein acts as a fine
      modulator of the dopaminergic synapse by regulating the subcellular distribution
      of key proteins such as the DAT.

PMID- 22163276
TI  - Impact of host cell line adaptation on quasispecies composition and glycosylation
      of influenza A virus hemagglutinin.
AB  - The genome of influenza A viruses is constantly changing (genetic drift)
      resulting in small, gradual changes in viral proteins. Alterations within
      antibody recognition sites of the viral membrane glycoproteins hemagglutinin (HA)
      and neuraminidase (NA) result in an antigenetic drift, which requires the
      seasonal update of human influenza virus vaccines. Generally, virus adaptation is
      necessary to obtain sufficiently high virus yields in cell culture-derived
      vaccine manufacturing. In this study detailed HA N-glycosylation pattern analysis
      was combined with in-depth pyrosequencing analysis of the virus genomic RNA.
      Forward and backward adaptation from Madin-Darby Canine Kidney (MDCK) cells to
      African green monkey kidney (Vero) cells was investigated for two closely related
      influenza A virus PR/8/34 (H1N1) strains: from the National Institute for
      Biological Standards and Control (NIBSC) or the Robert Koch Institute (RKI).
      Furthermore, stability of HA N-glycosylation patterns over ten consecutive
      passages and different harvest time points is demonstrated. Adaptation to Vero
      cells finally allowed efficient influenza A virus replication in Vero cells. In
      contrast, during back-adaptation the virus replicated well from the very
      beginning. HA N-glycosylation patterns were cell line dependent and stabilized
      fast within one (NIBSC-derived virus) or two (RKI-derived virus) successive
      passages during adaptation processes. However, during adaptation new virus
      variants were detected. These variants carried "rescue" mutations on the genomic
      level within the HA stem region, which result in amino acid substitutions. These
      substitutions finally allowed sufficient virus replication in the new host
      system. According to adaptation pressure the composition of the virus populations
      varied. In Vero cells a selection for "rescue" variants was characteristic. After
      back-adaptation to MDCK cells some variants persisted at indifferent frequencies,
      others slowly diminished and even dropped below the detection limit.

PMID- 22163277
TI  - Suppression of phospholipase Dgammas confers increased aluminum resistance in
      Arabidopsis thaliana.
AB  - Aluminum (Al) toxicity is the major stress in acidic soil that comprises about
      50% of the world's arable land. The complex molecular mechanisms of Al toxicity
      have yet to be fully determined. As a barrier to Al entrance, plant cell
      membranes play essential roles in plant interaction with Al, and lipid
      composition and membrane integrity change significantly under Al stress. Here, we
      show that phospholipase Dgammas (PLDgammas) are induced by Al stress and
      contribute to Al-induced membrane lipid alterations. RNAi suppression of PLDgamma
      resulted in a decrease in both PLDgamma1 and PLDgamma2 expression and an increase
      in Al resistance. Genetic disruption of PLDgamma1 also led to an increased
      tolerance to Al while knockout of PLDgamma2 did not. Both RNAi-suppressed and
      pldgamma1-1 mutants displayed better root growth than wild-type under Al stress
      conditions, and PLDgamma1-deficient plants had less accumulation of callose, less
      oxidative damage, and less lipid peroxidation compared to wild-type plants. Most
      phospholipids and glycolipids were altered in response to Al treatment of wild
      type plants, whereas fewer changes in lipids occurred in response to Al stress in
      PLDgamma mutant lines. Our results suggest that PLDgammas play a role in membrane
      lipid modulation under Al stress and that high activities of PLDgammas negatively
      modulate plant tolerance to Al.

PMID- 22163279
TI  - 6-year periodicity and variable synchronicity in a mass-flowering plant.
AB  - Periodical organisms, such as bamboos and periodical cicadas, are very famous for
      their synchronous reproduction. In bamboos and other periodical plants, the
      synchronicity of mass-flowering and withering has been often reported indicating
      these species are monocarpic (semelparous) species. Therefore, synchronicity and
      periodicity are often suspected to be fairly tightly coupled traits in these
      periodical plants. We investigate the periodicity and synchronicity of
      Strobilanthes flexicaulis, and a closely related species S. tashiroi on Okinawa
      Island, Japan. The genus Strobilanthes is known for several periodical species.
      Based on 32-year observational data, we confirmed that S. flexicaulis is 6-year
      periodical mass-flowering monocarpic plant. All the flowering plants had died
      after flowering. In contrast, we found that S. tashiroi is a polycarpic perennial
      with no mass-flowering from three-year individual tracking. We also surveyed six
      local populations of S. flexicaulis and found variation in the synchronicity from
      four highly synchronized populations (>98% of plants flowering in the mass year)
      to two less synchronized one with 11-47% of plants flowering before and after the
      mass year. This result might imply that synchrony may be selected for when
      periodicity is established in monocarpic species. We found the selective
      advantages for mass-flowering in pollinator activities and predator satiation.
      The current results suggest that the periodical S. flexicaulis might have evolved
      periodicity from a non-periodical close relative. The current report should
      become a key finding for understanding the evolution of periodical plants.

PMID- 22163278
TI  - A blood-based screening tool for Alzheimer's disease that spans serum and plasma:
      findings from TARC and ADNI.
AB  - CONTEXT: There is no rapid and cost effective tool that can be implemented as a
      front-line screening tool for Alzheimer's disease (AD) at the population level.
      OBJECTIVE: To generate and cross-validate a blood-based screener for AD that
      yields acceptable accuracy across both serum and plasma. DESIGN, SETTING,
      PARTICIPANTS: Analysis of serum biomarker proteins were conducted on 197
      Alzheimer's disease (AD) participants and 199 control participants from the Texas
      Alzheimer's Research Consortium (TARC) with further analysis conducted on plasma
      proteins from 112 AD and 52 control participants from the Alzheimer's Disease
      Neuroimaging Initiative (ADNI). The full algorithm was derived from a biomarker
      risk score, clinical lab (glucose, triglycerides, total cholesterol,
      homocysteine), and demographic (age, gender, education, APOE*E4 status) data.
      MAJOR OUTCOME MEASURES: Alzheimer's disease. RESULTS: 11 proteins met our
      criteria and were utilized for the biomarker risk score. The random forest (RF)
      biomarker risk score from the TARC serum samples (training set) yielded adequate
      accuracy in the ADNI plasma sample (training set) (AUC = 0.70, sensitivity (SN) =
      0.54 and specificity (SP) = 0.78), which was below that obtained from ADNI
      cerebral spinal fluid (CSF) analyses (t-tau/Abeta ratio AUC = 0.92). However, the
      full algorithm yielded excellent accuracy (AUC = 0.88, SN = 0.75, and SP = 0.91).
      The likelihood ratio of having AD based on a positive test finding (LR+) = 7.03
      (SE = 1.17; 95% CI = 4.49-14.47), the likelihood ratio of not having AD based on
      the algorithm (LR-) = 3.55 (SE = 1.15; 2.22-5.71), and the odds ratio of AD were
      calculated in the ADNI cohort (OR) = 28.70 (1.55; 95% CI = 11.86-69.47).
      CONCLUSIONS: It is possible to create a blood-based screening algorithm that
      works across both serum and plasma that provides a comparable screening accuracy
      to that obtained from CSF analyses.

PMID- 22163280
TI  - Genome-scale screen for DNA methylation-based detection markers for ovarian
      cancer.
AB  - BACKGROUND: The identification of sensitive biomarkers for the detection of
      ovarian cancer is of high clinical relevance for early detection and/or
      monitoring of disease recurrence. We developed a systematic multi-step biomarker
      discovery and verification strategy to identify candidate DNA methylation markers
      for the blood-based detection of ovarian cancer. METHODOLOGY/PRINCIPAL FINDINGS:
      We used the Illumina Infinium platform to analyze the DNA methylation status of
      27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy
      that emphasized sensitivity by requiring consistency of methylation across
      tumors, while achieving specificity by excluding markers with methylation in
      control leukocyte or serum DNA. Our verification strategy involved testing the
      ability of identified markers to monitor disease burden in serially collected
      serum samples from ovarian cancer patients who had undergone surgical tumor
      resection compared to CA-125 levels. We identified one marker, IFFO1 promoter
      methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that
      is rarely detected in the blood of normal controls. When tested in 127 serially
      collected sera from ovarian cancer patients, IFFO1-M showed post-resection
      kinetics significantly correlated with serum CA-125 measurements in six out of 16
      patients. CONCLUSIONS/SIGNIFICANCE: We implemented an effective marker screening
      and verification strategy, leading to the identification of IFFO1-M as a blood
      based candidate marker for sensitive detection of ovarian cancer. Serum levels of
      IFFO1-M displayed post-resection kinetics consistent with a reflection of disease
      burden. We anticipate that IFFO1-M and other candidate markers emerging from this
      marker development pipeline may provide disease detection capabilities that
      complement existing biomarkers.

PMID- 22163281
TI  - Genomic DNA methylation changes in response to folic acid supplementation in a
      population-based intervention study among women of reproductive age.
AB  - Folate is a source of one-carbons necessary for DNA methylation, a critical
      epigenetic modification necessary for genomic structure and function. The use of
      supplemental folic acid is widespread however; the potential influence on DNA
      methylation is unclear. We measured global DNA methylation using DNA extracted
      from samples from a population-based, double-blind randomized trial of folic acid
      supplementation (100, 400, 4000 ug per day) taken for 6 months; including a 3
      month post-supplementation sample. We observed no changes in global DNA
      methylation in response to up to 4,000 ug/day for 6 months supplementation in DNA
      extracted from uncoagulated blood (approximates circulating blood). However, when
      DNA methylation was determined in coagulated samples from the same individuals at
      the same time, significant time, dose, and MTHFR genotype-dependent changes were
      observed. The baseline level of DNA methylation was the same for uncoagulated and
      coagulated samples; marked differences between sample types were observed only
      after intervention. In DNA from coagulated blood, DNA methylation decreased (
      14%; P<0.001) after 1 month of supplementation and 3 months after supplement
      withdrawal, methylation decreased an additional 23% (P<0.001) with significant
      variation among individuals (max+17%; min-94%). Decreases in methylation of >=25%
      (vs. <25%) after discontinuation of supplementation were strongly associated with
      genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The
      unexpected difference in DNA methylation between DNA extracted from coagulated
      and uncoagulated samples in response to folic acid supplementation is an
      important finding for evaluating use of folic acid and investigating the
      potential effects of folic acid supplementation on coagulation.

PMID- 22163282
TI  - Role of NADPH oxidase versus neutrophil proteases in antimicrobial host defense.
AB  - NADPH oxidase is a crucial enzyme in mediating antimicrobial host defense and in
      regulating inflammation. Patients with chronic granulomatous disease, an
      inherited disorder of NADPH oxidase in which phagocytes are defective in
      generation of reactive oxidant intermediates (ROIs), suffer from life-threatening
      bacterial and fungal infections. The mechanisms by which NADPH oxidase mediate
      host defense are unclear. In addition to ROI generation, neutrophil NADPH oxidase
      activation is linked to the release of sequestered proteases that are posited to
      be critical effectors of host defense. To definitively determine the contribution
      of NADPH oxidase versus neutrophil serine proteases, we evaluated susceptibility
      to fungal and bacterial infection in mice with engineered disruptions of these
      pathways. NADPH oxidase-deficient mice (p47(phox-/-)) were highly susceptible to
      pulmonary infection with Aspergillus fumigatus. In contrast, double knockout
      neutrophil elastase (NE)(-/-)*cathepsin G (CG)(-/-) mice and lysosomal cysteine
      protease cathepsin C/dipeptidyl peptidase I (DPPI)-deficient mice that are
      defective in neutrophil serine protease activation demonstrated no impairment in
      antifungal host defense. In separate studies of systemic Burkholderia cepacia
      infection, uniform fatality occurred in p47(phox-/-) mice, whereas NE(-/-)*CG(-/
      ) mice cleared infection. Together, these results show a critical role for NADPH
      oxidase in antimicrobial host defense against A. fumigatus and B. cepacia,
      whereas the proteases we evaluated were dispensable. Our results indicate that
      NADPH oxidase dependent pathways separate from neutrophil serine protease
      activation are required for host defense against specific pathogens.

PMID- 22163283
TI  - Value of laboratory tests in employer-sponsored health risk assessments for newly
      identifying health conditions: analysis of 52,270 participants.
AB  - BACKGROUND: Employer-sponsored health risk assessments (HRA) may include
      laboratory tests to provide evidence of disease and disease risks for common
      medical conditions. We evaluated the ability of HRA-laboratory testing to provide
      new disease-risk information to participants. METHODOLOGY/PRINCIPAL FINDINGS: We
      performed a cross-sectional analysis of HRA-laboratory results for participating
      adult employees and their eligible spouses or their domestic partners, focusing
      on three common health conditions: hyperlipidemia, diabetes mellitus, and chronic
      kidney disease. HRA with laboratory results of 52,270 first-time participants
      were analyzed. Nearly all participants had access to health insurance coverage.
      Twenty-four percent (12,392) self-reported one or more of these medical
      conditions: 21.1% (11,017) self-identified as having hyperlipidemia, 4.7% (2,479)
      self-identified as having diabetes, and 0.7% (352) self-identified as having
      chronic kidney disease. Overall, 36% (n = 18,540) of participants had laboratory
      evidence of at least one medical condition newly identified: 30.7% (16,032) had
      laboratory evidence of hyperlipidemia identified, 1.9% (984) had laboratory
      evidence of diabetes identified, and 5.5% (2,866) had laboratory evidence of
      chronic kidney disease identified. Of all participants with evidence of
      hyperlipidemia 59% (16,030 of 27,047), were newly identified through the HRA.
      Among those with evidence of diabetes 28% (984 of 3,463) were newly identified.
      The highest rate of newly identified disease risk was for chronic kidney disease:
      89% (2,866 of 3,218) of participants with evidence of this condition had not self
      reported it. Men (39%) were more likely than women (33%) to have at least one
      newly identified condition (p<0.0001). Among men, lower levels of educational
      achievement were associated with modestly higher rates of newly identified
      disease risk (p<0.0001); the association with educational achievement among women
      was unclear. Even among the youngest age range (20 to 29 year olds), nearly 1 in
      4 participants (24%) had a newly identified risk for disease.
      CONCLUSIONS/SIGNIFICANCE: These results support the important role of employer
      sponsored laboratory testing as an integral element of HRA for identifying
      evidence of previously undiagnosed common medical conditions in individuals of
      all working age ranges, regardless of educational level and gender.

PMID- 22163284
TI  - Spatial orientation in Japanese quails (Coturnix coturnix japonica).
AB  - Finding a given location can be based on a variety of strategies, for example on
      the estimation of spatial relations between landmarks, called spatial
      orientation. In galliform birds, spatial orientation has been demonstrated
      convincingly in very young domestic chicks. We wanted to know whether adult
      Japanese quails (Coturnix coturnix japonica) without food deprivation are also
      able to use spatial orientation. The quails had to learn the relation of a food
      location with four conspicuous landmarks which were placed in the corners of a
      square shaped arena. They were trained to find mealworms in three adjacent food
      cups in a circle of 20 such cups. The rewarded feeders were located during
      training between the same two landmarks each of which showed a distinct pattern.
      When the birds had learned the task, all landmarks were displaced clockwise by 90
      degrees. When tested in the new situation, all birds redirected their choices
      with respect to the landmark shift. In subsequent tests, however, the previously
      correct position was also chosen. According to our results, quails are using
      conspicuous landmarks as a first choice for orientation. The orientation towards
      the previously rewarded location, however, indicates that the neuronal
      representation of space which is used by the birds also includes more fine grain,
      less conspicuous cues, which are probably also taken into account in uncertain
      situations. We also presume that the rare orientation towards never rewarded
      feeders may be due to a foraging strategy instead of being mistakes.

PMID- 22163285
TI  - The local origin of the Tibetan pig and additional insights into the origin of
      Asian pigs.
AB  - BACKGROUND: The domestic pig currently indigenous to the Tibetan highlands is
      supposed to have been introduced during a continuous period of colonization by
      the ancestors of modern Tibetans. However, there is no direct genetic evidence of
      either the local origin or exotic migration of the Tibetan pig. METHODS AND
      FINDINGS: We analyzed mtDNA hypervariable segment I (HVI) variation of 218
      individuals from seven Tibetan pig populations and 1,737 reported mtDNA sequences
      from domestic pigs and wild boars across Asia. The Bayesian consensus tree
      revealed a main haplogroup M and twelve minor haplogroups, which suggested a
      large number of small scale in situ domestication episodes. In particular,
      haplogroups D1 and D6 represented two highly divergent lineages in the Tibetan
      highlands and Island Southeastern Asia, respectively. Network analysis of
      haplogroup M further revealed one main subhaplogroup M1 and two minor
      subhaplogroups M2 and M3. Intriguingly, M2 was mainly distributed in Southeastern
      Asia, suggesting for a local origin. Similar with haplogroup D6, M3 was mainly
      restricted in Island Southeastern Asia. This pattern suggested that Island
      Southeastern Asia, but not Southeastern Asia, might be the center of
      domestication of the so-called Pacific clade (M3 and D6 here) described in
      previous studies. Diversity gradient analysis of major subhaplogroup M1 suggested
      three local origins in Southeastern Asia, the middle and downstream regions of
      the Yangtze River, and the Tibetan highlands, respectively. CONCLUSIONS: We
      identified two new origin centers for domestic pigs in the Tibetan highlands and
      in the Island Southeastern Asian region.

PMID- 22163286
TI  - Lightweight GPS-tags, one giant leap for wildlife tracking? An assessment
      approach.
AB  - Recent technological improvements have made possible the development of
      lightweight GPS-tagging devices suitable to track medium-to-small sized animals.
      However, current inferences concerning GPS performance are based on heavier
      designs, suitable only for large mammals. Lightweight GPS-units are deployed
      close to the ground, on species selecting micro-topographical features and with
      different behavioural patterns in comparison to larger mammal species. We
      assessed the effects of vegetation, topography, motion, and behaviour on the fix
      success rate for lightweight GPS-collar across a range of natural environments,
      and at the scale of perception of feral cats (Felis catus). Units deployed at 20
      cm above the ground in sites of varied vegetation and topography showed that
      trees (native forest) and shrub cover had the largest influence on fix success
      rate (89% on average); whereas tree cover, sky availability, number of satellites
      and horizontal dilution of position (HDOP) were the main variables affecting
      location error (+/-39.5 m and +/-27.6 m before and after filtering outlier
      fixes). Tests on HDOP or number of satellites-based screening methods to remove
      inaccurate locations achieved only a small reduction of error and discarded many
      accurate locations. Mobility tests were used to simulate cats' motion, revealing
      a slightly lower performance as compared to the fixed sites. GPS-collars deployed
      on 43 cats showed no difference in fix success rate by sex or season. Overall,
      fix success rate and location error values were within the range of previous
      tests carried out with collars designed for larger species. Lightweight GPS-tags
      are a suitable method to track medium to small size species, hence increasing the
      range of opportunities for spatial ecology research. However, the effects of
      vegetation, topography and behaviour on location error and fix success rate need
      to be evaluated prior to deployment, for the particular study species and their
      habitats.

PMID- 22163287
TI  - Species discrimination, population structure and linkage disequilibrium in
      Eucalyptus camaldulensis and Eucalyptus tereticornis using SSR markers.
AB  - Eucalyptus camaldulensis and E. tereticornis are closely related species commonly
      cultivated for pulp wood in many tropical countries including India.
      Understanding the genetic structure and linkage disequilibrium (LD) existing in
      these species is essential for the improvement of industrially important traits.
      Our goal was to evaluate the use of simple sequence repeat (SSR) loci for species
      discrimination, population structure and LD analysis in these species.
      Investigations were carried out with the most common alleles in 93 accessions
      belonging to these two species using 62 SSR markers through cross amplification.
      The polymorphic information content (PIC) ranged from 0.44 to 0.93 and 0.36 to
      0.93 in E. camaldulensis and E. tereticornis respectively. A clear delineation
      between the two species was evident based on the analysis of population structure
      and species-specific alleles. Significant genotypic LD was found in E.
      camaldulensis, wherein out of 135 significant pairs, 17 pairs showed r(2)>=0.1.
      Similarly, in E. tereticornis, out of 136 significant pairs, 18 pairs showed
      r(2)>=0.1. The extent of LD decayed rapidly showing the significance of
      association analyses in eucalypts with higher resolution markers. The
      availability of whole genome sequence for E. grandis and the synteny and co
      linearity in the genome of eucalypts, will allow genome-wide genotyping using
      microsatellites or single nucleotide polymorphims.

PMID- 22163288
TI  - Influence of conserved and hypervariable genetic markers on genotyping
      circulating strains of Neisseria gonorrhoeae.
AB  - Presently there is no vaccine against Neisseria gonorrhoeae and therefore
      accurate information on gonococcal transmission plays a crucial role for
      interventions designed to limit the spread of infections caused by this
      microorganism. We evaluated the impact of two different categories of genetic
      markers, (i) concatenated sequences of 10 housekeeping genes and (ii)
      hypervariable porB DNA sequences, on the genetic relatedness and subsequently on
      genotyping analysis of this human pathogen. Eighty gonococcal isolates from
      Canada, China, the US, Argentina, Venezuela and Chile, collected over different
      times, were analyzed. Our results show that the choice of genetic marker had a
      profound effect on the interpretation of genotyping results associated with N.
      gonorrhoeae. The concatenated sequences of the housekeeping genes preserved the
      genetic relatedness of closely related isolates, enabling detection of the
      predominant strains circulating within a community (Saskatchewan, Canada) over an
      extended period of time. In contrast, a genetic marker based on antigen gene,
      porB, may lead to a failure to detect these predominant circulating strains.
      Based on the analysis of the DNA sequences of the 10 housekeeping genes, we
      identified two major clonal complexes, CC33 and CC22, which comprised STs from
      China, and Argentina as well as two STs from Canada. Several minor clonal
      complexes were observed among isolates from Saskatchewan. eBURST analysis
      suggested that the majority of the tested gonococcal isolates from Saskatchewan,
      Canada were endemic, with only a couple of genotypes introduced.

PMID- 22163289
TI  - Disruption of spectrin-like cytoskeleton in differentiating keratinocytes by
      PKCdelta activation is associated with phosphorylated adducin.
AB  - Spectrin is a central component of the cytoskeletal protein network in a variety
      of erythroid and non-erythroid cells. In keratinocytes, this protein has been
      shown to be pericytoplasmic and plasma membrane associated, but its
      characteristics and function have not been established in these cells. Here we
      demonstrate that spectrin increases dramatically in amount and is assembled into
      the cytoskeleton during differentiation in mouse and human keratinocytes. The
      spectrin-like cytoskeleton was predominantly organized in the granular and
      cornified layers of the epidermis and disrupted by actin filament inhibitors, but
      not by anti-mitotic drugs. When the cytoskeleton was disrupted PKCdelta was
      activated by phosphorylation on Thr505. Specific inhibition of PKCdelta(Thr505)
      activation with rottlerin prevented disruption of the spectrin-like cytoskeleton
      and the associated morphological changes that accompany differentiation.
      Rottlerin also inhibited specific phosphorylation of the PKCdelta substrate
      adducin, a cytoskeletal protein. Furthermore, knock-down of endogenous adducin
      affected not only expression of adducin, but also spectrin and PKCdelta, and
      severely disrupted organization of the spectrin-like cytoskeleton and
      cytoskeletal distribution of both adducin and PKCdelta. These results demonstrate
      that organization of a spectrin-like cytoskeleton is associated with
      keratinocytes differentiation, and disruption of this cytoskeleton is mediated by
      either PKCdelta(Thr505) phosphorylation associated with phosphorylated adducin or
      due to reduction of endogenous adducin, which normally connects and stabilizes
      the spectrin-actin complex.

PMID- 22163290
TI  - Phylogenetic status and timescale for the diversification of Steno and Sotalia
      dolphins.
AB  - Molecular data have provided many insights into cetacean evolution but some
      unsettled issues still remain. We estimated the topology and timing of cetacean
      evolutionary relationships using bayesian and maximum likelihood analyses of
      complete mitochondrial genomes. In order to clarify the phylogenetic placement of
      Sotalia and Steno within the Delphinidae, we sequenced three new delphinid
      mitogenomes. Our analyses support three delphinid clades: one joining Steno and
      Sotalia (supporting the revised subfamily Stenoninae); another placing Sousa
      within the Delphininae; and a third, the Globicephalinae, which includes
      Globicephala, Feresa, Pseudorca, Peponocephala and Grampus. We also conclude that
      Orcinus does not belong in the Globicephalinae, but Orcaella may be part of that
      subfamily. Divergence dates were estimated using the relaxed molecular clock
      calibrated with fossil data. We hypothesise that the timing of separation of the
      marine and Amazonian Sotalia species (2.3 Ma) coincided with the establishment of
      the modern Amazon River basin.

PMID- 22163291
TI  - Calculating stage duration statistics in multistage diseases.
AB  - Many human diseases are characterized by multiple stages of progression. While
      the typical sequence of disease progression can be identified, there may be large
      individual variations among patients. Identifying mean stage durations and their
      variations is critical for statistical hypothesis testing needed to determine if
      treatment is having a significant effect on the progression, or if a new therapy
      is showing a delay of progression through a multistage disease. In this paper we
      focus on two methods for extracting stage duration statistics from longitudinal
      datasets: an extension of the linear regression technique, and a counting
      algorithm. Both are non-iterative, non-parametric and computationally cheap
      methods, which makes them invaluable tools for studying the epidemiology of
      diseases, with a goal of identifying different patterns of progression by using
      bioinformatics methodologies. Here we show that the regression method performs
      well for calculating the mean stage durations under a wide variety of
      assumptions, however, its generalization to variance calculations fails under
      realistic assumptions about the data collection procedure. On the other hand, the
      counting method yields reliable estimations for both means and variances of stage
      durations. Applications to Alzheimer disease progression are discussed.

PMID- 22163293
TI  - A simple but highly effective approach to evaluate the prognostic performance of
      gene expression signatures.
AB  - BACKGROUND: Highly parallel analysis of gene expression has recently been used to
      identify gene sets or 'signatures' to improve patient diagnosis and risk
      stratification. Once a signature is generated, traditional statistical testing is
      used to evaluate its prognostic performance. However, due to the dimensionality
      of microarrays, this can lead to false interpretation of these signatures.
      PRINCIPAL FINDINGS: A method was developed to test batches of a user-specified
      number of randomly chosen signatures in patient microarray datasets. The
      percentage of random generated signatures yielding prognostic value was assessed
      using ROC analysis by calculating the area under the curve (AUC) in six public
      available cancer patient microarray datasets. We found that a signature
      consisting of randomly selected genes has an average 10% chance of reaching
      significance when assessed in a single dataset, but can range from 1% to ~40%
      depending on the dataset in question. Increasing the number of validation
      datasets markedly reduces this number. CONCLUSIONS: We have shown that the use of
      an arbitrary cut-off value for evaluation of signature significance is not
      suitable for this type of research, but should be defined for each dataset
      separately. Our method can be used to establish and evaluate signature
      performance of any derived gene signature in a dataset by comparing its
      performance to thousands of randomly generated signatures. It will be of most
      interest for cases where few data are available and testing in multiple datasets
      is limited.

PMID- 22163292
TI  - DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with
      CD4.
AB  - Mannose-binding C-type lectin receptors, expressed on Langerhans cells and
      subepithelial dendritic cells (DCs) of cervico-vaginal tissues, play an important
      role in HIV-1 capture and subsequent dissemination to lymph nodes. DC-SIGN has
      been implicated in both productive infection of DCs and the DC-mediated trans
      infection of CD4(+) T cells that occurs in the absence of replication. However,
      the molecular events that underlie this efficient transmission have not been
      fully defined. In this study, we have examined the effect of the extracellular
      domains of DC-SIGN and Langerin on the stability of the interaction of the HIV-1
      envelope glycoprotein with CD4 and also on replication in permissive cells.
      Surface plasmon resonance analysis showed that DC-SIGN increases the binding
      affinity of trimeric gp140 envelope glycoproteins to CD4. In contrast, Langerin
      had no effect on the stability of the gp140:CD4 complex. In vitro infection
      experiments to compare DC-SIGN enhancement of CD4-dependent and CD4-independent
      strains demonstrated significantly lower enhancement of the CD4-independent
      strain. In addition DC-SIGN increased the relative rate of infection of the CD4
      dependent strain but had no effect on the CD4-independent strain. DC-SIGN binding
      to the HIV envelope protein effectively increases exposure of the CD4 binding
      site, which in turn contributes to enhancement of infection.

PMID- 22163294
TI  - Estrogenic plant extracts reverse weight gain and fat accumulation without
      causing mammary gland or uterine proliferation.
AB  - Long-term estrogen deficiency increases the risk of obesity, diabetes and
      metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing
      estrogens might prevent these conditions, but its prolonged use increases the
      risk of breast cancer, as wells as endometrial cancer if used without progestins.
      Animal studies indicate that beneficial effects of estrogens in adipose tissue
      and adverse effects on mammary gland and uterus are mediated by estrogen receptor
      alpha (ERalpha). One strategy to improve the safety of estrogens to prevent/treat
      obesity, diabetes and metabolic syndrome is to develop estrogens that act as
      agonists in adipose tissue, but not in mammary gland and uterus. We considered
      plant extracts, which have been the source of many pharmaceuticals, as a source
      of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis
      (RG) and Pueraria montana var. lobata (RP) bound to ERalpha, activated ERalpha
      responsive reporters, and reversed weight gain and fat accumulation comparable to
      estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike
      estradiol, RG and RP did not induce proliferative effects on mammary gland and
      uterus. Gene expression profiling demonstrated that RG and RP induced estradiol
      like regulation of genes in abdominal fat, but not in mammary gland and uterus.
      The compounds in extracts from RG and RP might constitute a new class of tissue
      selective estrogens to reverse weight gain, fat accumulation and metabolic
      syndrome in postmenopausal women.

PMID- 22163295
TI  - Following a foraging fish-finder: diel habitat use of Blainville's beaked whales
      revealed by echolocation.
AB  - Simultaneous high resolution sampling of predator behavior and habitat
      characteristics is often difficult to achieve despite its importance in
      understanding the foraging decisions and habitat use of predators. Here we tap
      into the biosonar system of Blainville's beaked whales, Mesoplodon densirostris,
      using sound and orientation recording tags to uncover prey-finding cues available
      to echolocating predators in the deep-sea. Echolocation sounds indicate where
      whales search and encounter prey, as well as the altitude of whales above the sea
      floor and the density of organisms around them, providing a link between foraging
      activity and the bio-physical environment. Tagged whales (n = 9) hunted
      exclusively at depth, investing most of their search time either in the lower
      part of the deep scattering layer (DSL) or near the sea-floor with little diel
      change. At least 43% (420/974) of recorded prey-capture attempts were performed
      within the benthic boundary layer despite a wide range of dive depths, and many
      dives included both meso- and bentho-pelagic foraging. Blainville's beaked whales
      only initiate searching when already deep in the descent and encounter prey
      suitable for capture within 2 min of the start of echolocation, suggesting that
      these whales are accessing prey in reliable vertical strata. Moreover, these prey
      resources are sufficiently dense to feed the animals in what is effectively four
      hours of hunting per day enabling a strategy in which long dives to exploit
      numerous deep-prey with low nutritional value require protracted recovery periods
      (average 1.5 h) between dives. This apparent searching efficiency maybe aided by
      inhabiting steep undersea slopes with access to both the DSL and the sea-floor
      over small spatial scales. Aggregations of prey in these biotopes are located
      using biosonar-derived landmarks and represent stable and abundant resources for
      Blainville's beaked whales in the otherwise food-limited deep-ocean.

PMID- 22163296
TI  - Behavioral mechanism during human sperm chemotaxis: involvement of
      hyperactivation.
AB  - When mammalian spermatozoa become capacitated they acquire, among other
      activities, chemotactic responsiveness and the ability to exhibit occasional
      events of hyperactivated motility--a vigorous motility type with large amplitudes
      of head displacement. Although a number of roles have been proposed for this type
      of motility, its function is still obscure. Here we provide evidence suggesting
      that hyperactivation is part of the chemotactic response. By analyzing tracks of
      spermatozoa swimming in a spatial chemoattractant gradient we demonstrate that,
      in such a gradient, the level of hyperactivation events is significantly lower
      than in proper controls. This suggests that upon sensing an increase in the
      chemoattractant concentration capacitated cells repress their hyperactivation
      events and thus maintain their course of swimming toward the chemoattractant.
      Furthermore, in response to a temporal concentration jump achieved by
      photorelease of the chemoattractant progesterone from its caged form, the
      responsive cells exhibited a delayed turn, often accompanied by hyperactivation
      events or an even more intense response in the form of flagellar arrest. This
      study suggests that the function of hyperactivation is to cause a rather sharp
      turn during the chemotactic response of capacitated cells so as to assist them to
      reorient according to the chemoattractant gradient. On the basis of these results
      a model for the behavior of spermatozoa responding to a spatial chemoattractant
      gradient is proposed.

PMID- 22163297
TI  - Dominance, biomass and extinction resistance determine the consequences of
      biodiversity loss for multiple coastal ecosystem processes.
AB  - Key ecosystem processes such as carbon and nutrient cycling could be
      deteriorating as a result of biodiversity loss. However, currently we lack the
      ability to predict the consequences of realistic species loss on ecosystem
      processes. The aim of this study was to test whether species contributions to
      community biomass can be used as surrogate measures of their contribution to
      ecosystem processes. These were gross community productivity in a salt marsh
      plant assemblage and an intertidal macroalgae assemblage; community clearance of
      microalgae in sessile suspension feeding invertebrate assemblage; and nutrient
      uptake in an intertidal macroalgae assemblage. We conducted a series of
      biodiversity manipulations that represented realistic species extinction
      sequences in each of the three contrasting assemblages. Species were removed in a
      subtractive fashion so that biomass was allowed to vary with each species
      removal, and key ecosystem processes were measured at each stage of community
      disassembly. The functional contribution of species was directly proportional to
      their contribution to community biomass in a 1:1 ratio, a relationship that was
      consistent across three contrasting marine ecosystems and three ecosystem
      processes. This suggests that the biomass contributed by a species to an
      assemblage can be used to approximately predict the proportional decline in an
      ecosystem process when that species is lost. Such predictions represent "worst
      case scenarios" because, over time, extinction resilient species can offset the
      loss of biomass associated with the extinction of competitors. We also modelled a
      "best case scenario" that accounts for compensatory responses by the extant
      species with the highest per capita contribution to ecosystem processes. These
      worst and best case scenarios could be used to predict the minimum and maximum
      species required to sustain threshold values of ecosystem processes in the
      future.

PMID- 22163298
TI  - Sex work during the 2010 FIFA World Cup: results from a three-wave cross
      sectional survey.
AB  - BACKGROUND: In the months leading up to the 2010 FIFA World Cup in South Africa,
      international media postulated that at least 40,000 foreign sex workers would
      enter South Africa, and that an increased HIV incidence would follow. To
      strengthen the evidence base of future HIV prevention and sexual health
      programmes during international sporting events, we monitored the supply and
      demand of female sex work in the weeks before, during and after the 2010 FIFA
      World Cup. METHODOLOGY/PRINCIPAL FINDINGS: We conducted three telephonic surveys
      of female sex workers advertising online and in local newspapers, in the last
      week of May, June and July 2010. The overall response rate was 73.4% (718/978).
      The number of sex workers advertising online was 5.9% higher during the World Cup
      than before. The client turnover rate did not change significantly during
      (adjusted rate ratio [aRR] = 1.05; 95%CI: 0.90-1.23) or after (aRR = 1.06; 95%CI:
      0.91-1.24) the World Cup. The fraction of non-South African sex workers declined
      during (adjusted odds ratio [aOR] = 0.50; 95%CI: 0.32-0.79) and after (aOR =
      0.56; 95%CI: 0.37-0.86) the World Cup. Relatively more clients were foreign
      during the World Cup among sex workers advertising in the newspapers (aOR = 2.74;
      95%CI: 1.37-5.48) but not among those advertising online (aOR = 1.06; 95%CI: 0.60
      1.90). Self-reported condom use was high (99.0%) at baseline, and did not change
      during (aOR = 1.07; 95% CI: 0.16-7.30) or after (aOR = 1.13; 95% CI: 0.16-8.10)
      the Word Cup. CONCLUSIONS/SIGNIFICANCE: Our findings do not provide evidence for
      mass-immigration of foreign sex workers advertising online and in local
      newspapers, nor a spike in sex work or risk of HIV transmission in this
      subpopulation of sex workers during the World Cup. Public health programmes
      focusing on sex work and HIV prevention during international sporting events
      should be based on evidence, not media-driven sensationalism that further
      heightens discrimination against sex workers and increases their vulnerability.

PMID- 22163299
TI  - Abrasive, silica phytoliths and the evolution of thick molar enamel in primates,
      with implications for the diet of Paranthropus boisei.
AB  - BACKGROUND: Primates--including fossil species of apes and hominins--show
      variation in their degree of molar enamel thickness, a trait long thought to
      reflect a diet of hard or tough foods. The early hominins demonstrated molar
      enamel thickness of moderate to extreme degrees, which suggested to most
      researchers that they ate hard foods obtained on or near the ground, such as
      nuts, seeds, tubers, and roots. We propose an alternative hypothesis--that the
      amount of phytoliths in foods correlates with the evolution of thick molar enamel
      in primates, although this effect is constrained by a species' degree of
      folivory. METHODOLOGY/PRINCIPAL FINDINGS: From a combination of dietary data and
      evidence for the levels of phytoliths in plant families in the literature, we
      calculated the percentage of plant foods rich in phytoliths in the diets of
      twelve extant primates with wide variation in their molar enamel thickness.
      Additional dietary data from the literature provided the percentage of each
      primate's diet made up of plants and of leaves. A statistical analysis of these
      variables showed that the amount of abrasive silica phytoliths in the diets of
      our sample primates correlated positively with the thickness of their molar
      enamel, constrained by the amount of leaves in their diet (R(2) = 0.875;
      p<.0006). CONCLUSIONS/SIGNIFICANCE: The need to resist abrasion from phytoliths
      appears to be a key selective force behind the evolution of thick molar enamel in
      primates. The extreme molar enamel thickness of the teeth of the East African
      hominin Paranthropus boisei, long thought to suggest a diet comprising
      predominantly hard objects, instead appears to indicate a diet with plants high
      in abrasive silica phytoliths.

PMID- 22163300
TI  - Onset and progression of behavioral and molecular phenotypes in a novel congenic
      R6/2 line exhibiting intergenerational CAG repeat stability.
AB  - In the present study we report on the use of speed congenics to generate a
      C57BL/6J congenic line of HD-model R6/2 mice carrying 110 CAG repeats, which
      uniquely exhibits minimal intergenerational instability. We also report the first
      identification of the R6/2 transgene insertion site. The relatively stable line
      of 110 CAG R6/2 mice was characterized for the onset of behavioral impairments in
      motor, cognitive and psychiatric-related phenotypes as well as the progression of
      disease-related impairments from 4 to 10 weeks of age. 110Q mice exhibited many
      of the phenotypes commonly associated with the R6/2 model including reduced
      activity and impairments in rotarod performance. The onset of many of the
      phenotypes occurred around 6 weeks and was progressive across age. In addition,
      some phenotypes were observed in mice as early as 4 weeks of age. The present
      study also reports the onset and progression of changes in several molecular
      phenotypes in the novel R6/2 mice and the association of these changes with
      behavioral symptom onset and progression. Data from TR-FRET suggest an
      association of mutant protein state changes (soluble versus aggregated) in
      disease onset and progression.

PMID- 22163301
TI  - Gene expression profiling of embryonic human neural stem cells and dopaminergic
      neurons from adult human substantia nigra.
AB  - Neural stem cells (NSC) with self-renewal and multipotent properties serve as an
      ideal cell source for transplantation to treat neurodegenerative insults such as
      Parkinson's disease. We used Agilent's and Illumina Whole Human Genome
      Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC
      at a single time point in culture, and a multicellular tissue from postmortem
      adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We
      identified 13525 up-regulated genes in both cell types of which 3737 (27.6%)
      genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the
      human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly
      up-regulated in both cell population. Careful analysis of the data that emerged
      using DAVID has permitted us to distinguish several genes and pathways that are
      involved in dopaminergic (DA) differentiation, and to identify the crucial
      signaling pathways that direct the process of differentiation. The set of genes
      expressed more highly at hENSC is enriched in molecules known or predicted to be
      involved in the M phase of the mitotic cell cycle. On the other hand, the genes
      enriched in SN cells include a different set of functional categories, namely
      synaptic transmission, central nervous system development, structural
      constituents of the myelin sheath, the internode region of axons, myelination,
      cell projection, cell somata, ion transport, and the voltage-gated ion channel
      complex. Our results were also compared with data from various databases, and
      between different types of arrays, Agilent versus Illumina. This approach has
      allowed us to confirm the consistency of our obtained results for a large number
      of genes that delineate the phenotypical differences of embryonic NSCs, and SN
      cells.

PMID- 22163302
TI  - Correlation network analysis applied to complex biofilm communities.
AB  - The complexity of the human microbiome makes it difficult to reveal
      organizational principles of the community and even more challenging to generate
      testable hypotheses. It has been suggested that in the gut microbiome species
      such as Bacteroides thetaiotaomicron are keystone in maintaining the stability
      and functional adaptability of the microbial community. In this study, we
      investigate the interspecies associations in a complex microbial biofilm applying
      systems biology principles. Using correlation network analysis we identified
      bacterial modules that represent important microbial associations within the oral
      community. We used dental plaque as a model community because of its high
      diversity and the well known species-species interactions that are common in the
      oral biofilm. We analyzed samples from healthy individuals as well as from
      patients with periodontitis, a polymicrobial disease. Using results obtained by
      checkerboard hybridization on cultivable bacteria we identified modules that
      correlated well with microbial complexes previously described. Furthermore, we
      extended our analysis using the Human Oral Microbe Identification Microarray
      (HOMIM), which includes a large number of bacterial species, among them
      uncultivated organisms present in the mouth. Two distinct microbial communities
      appeared in healthy individuals while there was one major type in disease.
      Bacterial modules in all communities did not overlap, indicating that bacteria
      were able to effectively re-associate with new partners depending on the
      environmental conditions. We then identified hubs that could act as keystone
      species in the bacterial modules. Based on those results we then cultured a not
      yet-cultivated microorganism, Tannerella sp. OT286 (clone BU063). After two
      rounds of enrichment by a selected helper (Prevotella oris OT311) we obtained
      colonies of Tannerella sp. OT286 growing on blood agar plates. This system-level
      approach would open the possibility of manipulating microbial communities in a
      targeted fashion as well as associating certain bacterial modules to clinical
      traits (e.g.: obesity, Crohn's disease, periodontal disease, etc).

PMID- 22163303
TI  - Dendrimer-based fluorescent indicators: in vitro and in vivo applications.
AB  - BACKGROUND: The development of fluorescent proteins and synthetic molecules whose
      fluorescence properties are controlled by the environment makes it possible to
      monitor physiological and pathological events in living systems with minimal
      perturbation. A large number of small organic dyes are available and routinely
      used to measure biologically relevant parameters. Unfortunately their application
      is hindered by a number of limitations stemming from the use of these small
      molecules in the biological environment. PRINCIPAL FINDINGS: We present a novel
      dendrimer-based architecture leading to multifunctional sensing elements that can
      overcome many of these problems. Applications in vitro, in living cells and in
      vivo are reported. In particular, we image for the first time extracellular pH in
      the brain in a mouse epilepsy model. CONCLUSION: We believe that the proposed
      architecture can represent a useful and novel tool in fluorescence imaging that
      can be widely applied in conjunction with a broad range of sensing dyes and
      experimental setups.

PMID- 22163304
TI  - Omega-3 fatty acid deficiency during brain maturation reduces neuronal and
      behavioral plasticity in adulthood.
AB  - Omega-3-fatty acid DHA is a structural component of brain plasma membranes,
      thereby crucial for neuronal signaling; however, the brain is inefficient at
      synthesizing DHA. We have asked how levels of dietary n-3 fatty acids during
      brain growth would affect brain function and plasticity during adult life.
      Pregnant rats and their male offspring were fed an n-3 adequate diet or n-3
      deficient diets for 15 weeks. Results showed that the n-3 deficiency increased
      parameters of anxiety-like behavior using open field and elevated plus maze tests
      in the male offspring. Behavioral changes were accompanied by a level reduction
      in the anxiolytic-related neuropeptide Y-1 receptor, and an increase in the
      anxiogenic-related glucocorticoid receptor in the cognitive related frontal
      cortex, hypothalamus and hippocampus. The n-3 deficiency reduced brain levels of
      docosahexaenoic acid (DHA) and increased the ratio n-6/n-3 assessed by gas
      chromatography. The n-3 deficiency reduced the levels of BDNF and signaling
      through the BDNF receptor TrkB, in proportion to brain DHA levels, and reduced
      the activation of the BDNF-related signaling molecule CREB in selected brain
      regions. The n-3 deficiency also disrupted the insulin signaling pathways as
      evidenced by changes in insulin receptor (IR) and insulin receptor substrate
      (IRS). DHA deficiency during brain maturation reduces plasticity and compromises
      brain function in adulthood. Adequate levels of dietary DHA seem crucial for
      building long-term neuronal resilience for optimal brain performance and aiding
      in the battle against neurological disorders.

PMID- 22163305
TI  - Should the arteriovenous fistula be created before starting dialysis?: a decision
      analytic approach.
AB  - BACKGROUND: An arteriovenous fistula (AVF) is considered the vascular access of
      choice, but uncertainty exists about the optimal time for its creation in pre
      dialysis patients. The aim of this study was to determine the optimal vascular
      access referral strategy for stage 4 (glomerular filtration rate <30 ml/min/1.73
      m(2)) chronic kidney disease patients using a decision analytic framework.
      METHODS: A Markov model was created to compare two strategies: refer all stage 4
      chronic kidney disease patients for an AVF versus wait until the patient starts
      dialysis. Data from published observational studies were used to estimate the
      probabilities used in the model. A Markov cohort analysis was used to determine
      the optimal strategy with life expectancy and quality adjusted life expectancy as
      the outcomes. Sensitivity analyses, including a probabilistic sensitivity
      analysis, were performed using Monte Carlo simulation. RESULTS: The wait strategy
      results in a higher life expectancy (66.6 versus 65.9 months) and quality
      adjusted life expectancy (38.9 versus 38.5 quality adjusted life months) than
      immediate AVF creation. It was robust across all the parameters except at higher
      rates of progression and lower rates of ischemic steal syndrome. CONCLUSIONS:
      Early creation of an AVF, as recommended by most guidelines, may not be the
      preferred strategy in all pre-dialysis patients. Further research on cost
      implications and patient preferences for treatment options needs to be done
      before recommending early AVF creation.

PMID- 22163306
TI  - Antibody labelling of resilin in energy stores for jumping in plant sucking
      insects.
AB  - The rubbery protein resilin appears to form an integral part of the energy
      storage structures that enable many insects to jump by using a catapult
      mechanism. In plant sucking bugs that jump (Hemiptera, Auchenorrhyncha), the
      energy generated by the slow contractions of huge thoracic jumping muscles is
      stored by bending composite bow-shaped parts of the internal thoracic skeleton.
      Sudden recoil of these bows powers the rapid and simultaneous movements of both
      hind legs that in turn propel a jump. Until now, identification of resilin at
      these storage sites has depended exclusively upon characteristics that may not be
      specific: its fluorescence when illuminated with specific wavelengths of
      ultraviolet (UV) light and extinction of that fluorescence at low pH. To
      consolidate identification we have labelled the cuticular structures involved
      with an antibody raised against a product of the Drosophila CG15920 gene. This
      encodes pro-resilin, the first exon of which was expressed in E. coli and used to
      raise the antibody. We show that in frozen sections from two species, the
      antibody labels precisely those parts of the metathoracic energy stores that
      fluoresce under UV illumination. The presence of resilin in these insects is thus
      now further supported by a molecular criterion that is immunohistochemically
      specific.

PMID- 22163307
TI  - Yawn contagion and empathy in Homo sapiens.
AB  - The ability to share others' emotions, or empathy, is crucial for complex social
      interactions. Clinical, psychological, and neurobiological clues suggest a link
      between yawn contagion and empathy in humans (Homo sapiens). However, no
      behavioral evidence has been provided so far. We tested the effect of different
      variables (e.g., country of origin, sex, yawn characteristics) on yawn contagion
      by running mixed models applied to observational data collected over 1 year on
      adult (>16 years old) human subjects. Only social bonding predicted the
      occurrence, frequency, and latency of yawn contagion. As with other measures of
      empathy, the rate of contagion was greatest in response to kin, then friends,
      then acquaintances, and lastly strangers. Related individuals (r>=0.25) showed
      the greatest contagion, in terms of both occurrence of yawning and frequency of
      yawns. Strangers and acquaintances showed a longer delay in the yawn response
      (latency) compared to friends and kin. This outcome suggests that the neuronal
      activation magnitude related to yawn contagion can differ as a function of
      subject familiarity. In conclusion, our results demonstrate that yawn contagion
      is primarily driven by the emotional closeness between individuals and not by
      other variables, such as gender and nationality.

PMID- 22163308
TI  - Determinants of habitat selection by hatchling Australian freshwater crocodiles.
AB  - Animals almost always use habitats non-randomly, but the costs and benefits of
      using specific habitat types remain unknown for many types of organisms. In a
      large lake in northwestern Australia (Lake Argyle), most hatchling (<12-month
      old) freshwater crocodiles (Crocodylus johnstoni) are found in floating
      vegetation mats or grassy banks rather than the more widely available open banks.
      Mean body sizes of young crocodiles did not differ among the three habitat types.
      We tested four potential explanations for non-random habitat selection: proximity
      to nesting sites, thermal conditions, food availability, and exposure to
      predation. The three alternative habitat types did not differ in proximity to
      nesting sites, or in thermal conditions. Habitats with higher food availability
      harboured more hatchlings, and feeding rates (obtained by stomach-flushing of
      recently-captured crocodiles) were highest in such areas. Predation risk may also
      differ among habitats: we were twice as likely to capture a crocodile after
      seeing it in open-bank sites than in the other two habitat types. Thus, habitat
      selection of hatchling crocodiles in this system may be driven both by prey
      availability and by predation risk.

PMID- 22163309
TI  - Elevational ranges of birds on a tropical montane gradient lag behind warming
      temperatures.
AB  - BACKGROUND: Species may respond to a warming climate by moving to higher
      latitudes or elevations. Shifts in geographic ranges are common responses in
      temperate regions. For the tropics, latitudinal temperature gradients are
      shallow; the only escape for species may be to move to higher elevations. There
      are few data to suggest that they do. Yet, the greatest loss of species from
      climate disruption may be for tropical montane species. METHODOLOGY/PRINCIPAL
      FINDINGS: We repeat a historical transect in Peru and find an average upward
      shift of 49 m for 55 bird species over a 41 year interval. This shift is
      significantly upward, but also significantly smaller than the 152 m one expects
      from warming in the region. To estimate the expected shift in elevation we first
      determined the magnitude of warming in the locality from historical data. Then we
      used the temperature lapse rate to infer the required shift in altitude to
      compensate for warming. The range shifts in elevation were similar across
      different trophic guilds. CONCLUSIONS: Endothermy may provide birds with some
      flexibility to temperature changes and allow them to move less than expected.
      Instead of being directly dependent on temperature, birds may be responding to
      gradual changes in the nature of the habitat or availability of food resources,
      and presence of competitors. If so, this has important implications for estimates
      of mountaintop extinctions from climate change.

PMID- 22163310
TI  - Isolation of radial glia-like neural stem cells from fetal and adult mouse
      forebrain via selective adhesion to a novel adhesive peptide-conjugate.
AB  - Preferential adhesion of neural stem cells to surfaces covered with a novel
      synthetic adhesive polypeptide (AK-cyclo[RGDfC]) provided a unique, rapid
      procedure for isolating radial glia-like cells from both fetal and adult rodent
      brain. Radial glia-like (RGl) neural stem/progenitor cells grew readily on the
      peptide-covered surfaces under serum-free culture conditions in the presence of
      EGF as the only growth factor supplement. Proliferating cells derived either from
      fetal (E 14.5) forebrain or from different regions of the adult brain maintained
      several radial glia-specific features including nestin, RC2 immunoreactivity and
      Pax6, Sox2, Blbp, Glast gene expression. Proliferating RGl cells were obtained
      also from non-neurogenic zones including the parenchyma of the adult cerebral
      cortex and dorsal midbrain. Continuous proliferation allowed isolating one-cell
      derived clones of radial glia-like cells. All clones generated neurons,
      astrocytes and oligodendrocytes under appropriate inducing conditions.
      Electrophysiological characterization indicated that passive conductance with
      large delayed rectifying potassium current might be a uniform feature of non
      induced radial glia-like cells. Upon induction, all clones gave rise to GABAergic
      neurons. Significant differences were found, however, among the clones in the
      generation of glutamatergic and cathecolamine-synthesizing neurons and in the
      production of oligodendrocytes.

PMID- 22163311
TI  - DNA barcode detects high genetic structure within neotropical bird species.
AB  - BACKGROUND: Towards lower latitudes the number of recognized species is not only
      higher, but also phylogeographic subdivision within species is more pronounced.
      Moreover, new genetically isolated populations are often described in recent
      phylogenies of Neotropical birds suggesting that the number of species in the
      region is underestimated. Previous COI barcoding of Argentinean bird species
      showed more complex patterns of regional divergence in the Neotropical than in
      the North American avifauna. METHODS AND FINDINGS: Here we analyzed 1,431 samples
      from 561 different species to extend the Neotropical bird barcode survey to lower
      latitudes, and detected even higher geographic structure within species than
      reported previously. About 93% (520) of the species were identified correctly
      from their DNA barcodes. The remaining 41 species were not monophyletic in their
      COI sequences because they shared barcode sequences with closely related species
      (N = 21) or contained very divergent clusters suggestive of putative new species
      embedded within the gene tree (N = 20). Deep intraspecific divergences
      overlapping with among-species differences were detected in 48 species, often
      with samples from large geographic areas and several including multiple
      subspecies. This strong population genetic structure often coincided with breaks
      between different ecoregions or areas of endemism. CONCLUSIONS: The taxonomic
      uncertainty associated with the high incidence of non-monophyletic species and
      discovery of putative species obscures studies of historical patterns of species
      diversification in the Neotropical region. We showed that COI barcodes are a
      valuable tool to indicate which taxa would benefit from more extensive taxonomic
      revisions with multilocus approaches. Moreover, our results support hypotheses
      that the megadiversity of birds in the region is associated with multiple
      geographic processes starting well before the Quaternary and extending to more
      recent geological periods.

PMID- 22163312
TI  - Sequence features of E. coli mRNAs affect their degradation.
AB  - Degradation of mRNA in bacteria is a regulatory mechanism, providing an efficient
      way to fine-tune protein abundance in response to environmental changes. While
      the mechanisms responsible for initiation and subsequent propagation of mRNA
      degradation are well studied, the mRNA features that affect its stability are yet
      to be elucidated. We calculated three properties for each mRNA in the E. coli
      transcriptome: G+C content, tRNA adaptation index (tAI) and folding energy. Each
      of these properties were then correlated with the experimental transcript half
      life measured for each transcript and detected significant correlations. A
      sliding window analysis identified the regions that displayed the maximal signal.
      The correlation between transcript half life and both G+C content and folding
      energy was strongest at the 5' termini of the mRNAs. Partial correlations showed
      that each of the parameters contributes separately to mRNA half life. Notably,
      mRNAs of recently-acquired genes in the E. coli genome, which have a distinct
      nucleotide composition, tend to be highly stable. This high stability may aid the
      evolutionary fixation of horizontally acquired genes.

PMID- 22163313
TI  - Whole genome sequence analysis of Cryptococcus gattii from the Pacific Northwest
      reveals unexpected diversity.
AB  - A recent emergence of Cryptococcus gattii in the Pacific Northwest involves
      strains that fall into three primarily clonal molecular subtypes: VGIIa, VGIIb
      and VGIIc. Multilocus sequence typing (MLST) and variable number tandem repeat
      analysis appear to identify little diversity within these molecular subtypes.
      Given the apparent expansion of these subtypes into new geographic areas and
      their ability to cause disease in immunocompetent individuals, differentiation of
      isolates belonging to these subtypes could be very important from a public health
      perspective. We used whole genome sequence typing (WGST) to perform fine-scale
      phylogenetic analysis on 20 C. gattii isolates, 18 of which are from the VGII
      molecular type largely responsible for the Pacific Northwest emergence. Analysis
      both including and excluding (289,586 SNPs and 56,845 SNPs, respectively)
      molecular types VGI and VGIII isolates resulted in phylogenetic reconstructions
      consistent, for the most part, with MLST analysis but with far greater resolution
      among isolates. The WGST analysis presented here resulted in identification of
      over 100 SNPs among eight VGIIc isolates as well as unique genotypes for each of
      the VGIIa, VGIIb and VGIIc isolates. Similar levels of genetic diversity were
      found within each of the molecular subtype isolates, despite the fact that the
      VGIIb clade is thought to have emerged much earlier. The analysis presented here
      is the first multi-genome WGST study to focus on the C. gattii molecular subtypes
      involved in the Pacific Northwest emergence and describes the tools that will
      further our understanding of this emerging pathogen.

PMID- 22163314
TI  - Behavioural response thresholds in New Zealand crab megalopae to ambient
      underwater sound.
AB  - A small number of studies have demonstrated that settlement stage decapod
      crustaceans are able to detect and exhibit swimming, settlement and metamorphosis
      responses to ambient underwater sound emanating from coastal reefs. However, the
      intensity of the acoustic cue required to initiate the settlement and
      metamorphosis response, and therefore the potential range over which this
      acoustic cue may operate, is not known. The current study determined the
      behavioural response thresholds of four species of New Zealand brachyuran crab
      megalopae by exposing them to different intensity levels of broadcast reef sound
      recorded from their preferred settlement habitat and from an unfavourable
      settlement habitat. Megalopae of the rocky-reef crab, Leptograpsus variegatus,
      exhibited the lowest behavioural response threshold (highest sensitivity), with a
      significant reduction in time to metamorphosis (TTM) when exposed to underwater
      reef sound with an intensity of 90 dB re 1 uPa and greater (100, 126 and 135 dB
      re 1 uPa). Megalopae of the mud crab, Austrohelice crassa, which settle in soft
      sediment habitats, exhibited no response to any of the underwater reef sound
      levels. All reef associated species exposed to sound levels from an unfavourable
      settlement habitat showed no significant change in TTM, even at intensities that
      were similar to their preferred reef sound for which reductions in TTM were
      observed. These results indicated that megalopae were able to discern and respond
      selectively to habitat-specific acoustic cues. The settlement and metamorphosis
      behavioural response thresholds to levels of underwater reef sound determined in
      the current study of four species of crabs, enables preliminary estimation of the
      spatial range at which an acoustic settlement cue may be operating, from 5 m to
      40 km depending on the species. Overall, these results indicate that underwater
      sound is likely to play a major role in influencing the spatial patterns of
      settlement of coastal crab species.

PMID- 22163315
TI  - Tracking blood glucose and predicting prediabetes in Chinese children and
      adolescents: a prospective twin study.
AB  - We examined the tracking of blood glucose, the development of prediabetes, and
      estimated their genetic contributions in a prospective, healthy, rural Chinese
      twin cohort. This report includes 1,766 subjects (998 males, 768 females) aged 6
      21 years at baseline who completed a 6-year follow-up study. Oral glucose
      tolerance test was performed for all subjects at both baseline and follow-up. We
      found that subjects with low fasting plasma glucose (FPG) or 2 h post-load
      glucose (PG) levels at baseline tended to remain at the low level at follow-up.
      Subjects in the top tertile of baseline plasma glucose tended to have a higher
      risk of developing prediabetes at follow-up compared to the low tertile: in
      males, 37.6% vs. 27.6% for FPG and 37.2% vs. 25.7% for 2hPG, respectively; in
      females, 31.0% vs. 15.4% for FPG and 28.9% vs. 15.1% for 2 h PG, respectively.
      Genetic factors explained 43% and 41% of the variance of FPG, and 72% and 47% for
      impaired fasting glucose for males and females, respectively; environmental
      factors substantially contribute to 2hPG status and impaired glucose tolerance.
      In conclusion, in this cohort of healthy rural Chinese children and adolescents,
      we demonstrated that both FPG and 2hPG tracked well and was a strong predictor of
      prediabetes. The high proportion of children with top tertile of blood glucose
      progressed to prediabetes, and the incidence of prediabetes has a male
      predominance. Genetic factors play more important role in fasting than postload
      status, most of which was explained by unique environmental factors.

PMID- 22163317
TI  - Two-way minimization: a novel treatment allocation method for small trials.
AB  - Randomization is a hallmark of clinical trials. If a trial entails very few
      subjects and has many prognostic factors (or many factor levels) to be balanced,
      minimization is a more efficient method to achieve balance than a simple
      randomization. We propose a novel minimization method, the 'two-way
      minimization'. The method separately calculates the 'imbalance in the total
      numbers of subjects' and the 'imbalance in the distributions of prognostic
      factors'. And then to allocate a subject, it chooses--by probability--to minimize
      either one of these two aspects of imbalances. As such, it is a method that is
      both treatment-adaptive and covariate-adaptive. We perform Monte-Carlo
      simulations to examine its statistical properties. The two-way minimization (with
      proper regression adjustment of the force-balanced prognostic factors) has the
      correct type I error rates. It also produces point estimates that are unbiased
      and variance estimates that are accurate. When there are important prognostic
      factors to be balanced in the study, the method achieves the highest power and
      the smallest variance among randomization methods that are resistant to selection
      bias. The allocation can be done in real time and the subsequent data analysis is
      straightforward. The two-way minimization is recommended to balance prognostic
      factors in small trials.

PMID- 22163316
TI  - Phosphorylation of AIB1 at mitosis is regulated by CDK1/CYCLIN B.
AB  - BACKGROUND: Although the AIB1 oncogene has an important role during the early
      phase of the cell cycle as a coactivator of E2F1, little is known about its
      function during mitosis. METHODOLOGY/PRINCIPAL FINDINGS: Mitotic cells isolated
      by nocodazole treatment as well as by shake-off revealed a post-translational
      modification occurring in AIB1 specifically during mitosis. This modification was
      sensitive to the treatment with phosphatase, suggesting its modification by
      phosphorylation. Using specific inhibitors and in vitro kinase assays we
      demonstrate that AIB1 is phosphorylated on Ser728 and Ser867 by Cdk1/cyclin B at
      the onset of mitosis and remains phosphorylated until exit from M phase.
      Differences in the sensitivity to phosphatase inhibitors suggest that PP1
      mediates dephosphorylation of AIB1 at the end of mitosis. The phosphorylation of
      AIB1 during mitosis was not associated with ubiquitylation or degradation, as
      confirmed by western blotting and flow cytometry analysis. In addition,
      luciferase reporter assays showed that this phosphorylation did not alter the
      transcriptional properties of AIB1. Importantly, fluorescence microscopy and sub
      cellular fractionation showed that AIB1 phosphorylation correlated with the
      exclusion from the condensed chromatin, thus preventing access to the promoters
      of AIB1-dependent genes. Phospho-specific antibodies developed against Ser728
      further demonstrated the presence of phosphorylated AIB1 only in mitotic cells
      where it was localized preferentially in the periphery of the cell. CONCLUSIONS:
      Collectively, our results describe a new mechanism for the regulation of AIB1
      during mitosis, whereby phosphorylation of AIB1 by Cdk1 correlates with the
      subcellular redistribution of AIB1 from a chromatin-associated state in
      interphase to a more peripheral localization during mitosis. At the exit of
      mitosis, AIB1 is dephosphorylated, presumably by PP1. This exclusion from
      chromatin during mitosis may represent a mechanism for governing the
      transcriptional activity of AIB1.

PMID- 22163318
TI  - Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible
      memory deficit.
AB  - The translocation of synaptic Zn(2+) to the cytosolic compartment has been
      studied to understand Zn(2+) neurotoxicity in neurological diseases. However, it
      is unknown whether the moderate increase in Zn(2+) in the cytosolic compartment
      affects memory processing in the hippocampus. In the present study, the moderate
      increase in cytosolic Zn(2+) in the hippocampus was induced with clioquinol (CQ),
      a zinc ionophore. Zn(2+) delivery by Zn-CQ transiently attenuated CA1 long-term
      potentiation (LTP) in hippocampal slices prepared 2 h after i.p. injection of Zn
      CQ into rats, when intracellular Zn(2+) levels was transiently increased in the
      CA1 pyramidal cell layer, followed by object recognition memory deficit. Object
      recognition memory was transiently impaired 30 min after injection of ZnCl(2)
      into the CA1, but not after injection into the dentate gyrus that did not
      significantly increase intracellular Zn(2+) in the granule cell layer of the
      dentate gyrus. Object recognition memory deficit may be linked to the
      preferential increase in Zn(2+) and/or the preferential vulnerability to Zn(2+)
      in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous
      Zn(2+) in the CA1 induced by 100 mM KCl, furthermore, object recognition memory
      was also transiently impaired, while ameliorated by co-injection of CaEDTA to
      block the increase in cytosolic Zn(2+). The present study indicates that the
      transient increase in cytosolic Zn(2+) in CA1 pyramidal neurons reversibly
      impairs object recognition memory.

PMID- 22163319
TI  - Time estimation predicts mathematical intelligence.
AB  - BACKGROUND: Performing mental subtractions affects time (duration) estimates, and
      making time estimates disrupts mental subtractions. This interaction has been
      attributed to the concurrent involvement of time estimation and arithmetic with
      general intelligence and working memory. Given the extant evidence of a
      relationship between time and number, here we test the stronger hypothesis that
      time estimation correlates specifically with mathematical intelligence, and not
      with general intelligence or working-memory capacity. METHODOLOGY/PRINCIPAL
      FINDINGS: Participants performed a (prospective) time estimation experiment,
      completed several subtests of the WAIS intelligence test, and self-rated their
      mathematical skill. For five different durations, we found that time estimation
      correlated with both arithmetic ability and self-rated mathematical skill.
      Controlling for non-mathematical intelligence (including working memory capacity)
      did not change the results. Conversely, correlations between time estimation and
      non-mathematical intelligence either were nonsignificant, or disappeared after
      controlling for mathematical intelligence. CONCLUSIONS/SIGNIFICANCE: We conclude
      that time estimation specifically predicts mathematical intelligence. On the
      basis of the relevant literature, we furthermore conclude that the relationship
      between time estimation and mathematical intelligence is likely due to a common
      reliance on spatial ability.

PMID- 22163320
TI  - Srv mediated dispersal of streptococcal biofilms through SpeB is observed in
      CovRS+ strains.
AB  - Group A Streptococcus (GAS) is a human specific pathogen capable of causing both
      mild infections and severe invasive disease. We and others have shown that GAS is
      able to form biofilms during infection. That is to say, they form a three
      dimensional, surface attached structure consisting of bacteria and a multi
      component extracellular matrix. The mechanisms involved in regulation and
      dispersal of these GAS structures are still unclear. Recently we have reported
      that in the absence of the transcriptional regulator Srv in the MGAS5005
      background, the cysteine protease SpeB is constitutively produced, leading to
      increased tissue damage and decreased biofilm formation during a subcutaneous
      infection in a mouse model. This was interesting because MGAS5005 has a naturally
      occurring mutation that inactivates the sensor kinase domain of the two component
      regulatory system CovRS. Others have previously shown that strains lacking covS
      are associated with decreased SpeB production due to CovR repression of speB
      expression. Thus, our results suggest the inactivation of srv can bypass CovR
      repression and lead to constitutive SpeB production. We hypothesized that Srv
      control of SpeB production may be a mechanism to regulate biofilm dispersal and
      provide a mechanism by which mild infection can transition to severe disease
      through biofilm dispersal. The question remained however, is this mechanism
      conserved among GAS strains or restricted to the unique genetic makeup of
      MGAS5005. Here we show that Srv mediated control of SpeB and biofilm dispersal is
      conserved in the invasive clinical isolates RGAS053 (serotype M1) and MGAS315
      (serotype M3), both of which have covS intact. This work provides additional
      evidence that Srv regulated control of SpeB may mediate biofilm formation and
      dispersal in diverse strain backgrounds.

PMID- 22163321
TI  - Lunar phase-dependent expression of cryptochrome and a photoperiodic mechanism
      for lunar phase-recognition in a reef fish, goldlined spinefoot.
AB  - Lunar cycle-associated physiology has been found in a wide variety of organisms.
      Recent study has revealed that mRNA levels of Cryptochrome (Cry), one of the
      circadian clock genes, were significantly higher on a full moon night than on a
      new moon night in coral, implying the involvement of a photoreception system in
      the lunar-synchronized spawning. To better establish the generalities surrounding
      such a mechanism and explore the underlying molecular mechanism, we focused on
      the relationship between lunar phase, Cry gene expression, and the spawning
      behavior in a lunar-synchronized spawner, the goldlined spinefoot (Siganus
      guttatus), and we identified two kinds of Cry genes in this animal. Their mRNA
      levels showed lunar cycle-dependent expression in the medial part of the brain
      (mesencephalon and diencephalon) peaking at the first quarter moon. Since this
      lunar phase coincided with the reproductive phase of the goldlined spinefoot, Cry
      gene expression was considered a state variable in the lunar phase recognition
      system. Based on the expression profiles of SgCrys together with the moonlight's
      pattern of timing and duration during its nightly lunar cycle, we have further
      speculated on a model of lunar phase recognition for reproductive control in the
      goldlined spinefoot, which integrates both moonlight and circadian signals in a
      manner similar to photoperiodic response.

PMID- 22163322
TI  - Molecular evolution of the infrared sensory gene TRPA1 in snakes and implications
      for functional studies.
AB  - TRPA1 is a calcium ion channel protein recently identified as the infrared
      receptor in pit organ-containing snakes. Therefore, understanding the molecular
      evolution of TRPA1 may help to illuminate the origin of "heat vision" in snakes
      and reveal the molecular mechanism of infrared sensitivity for TRPA1. To this
      end, we sequenced the infrared sensory gene TRPA1 in 24 snake species,
      representing nine snake families and multiple non-snake outgroups. We found that
      TRPA1 is under strong positive selection in the pit-bearing snakes studied, but
      not in other non-pit snakes and non-snake vertebrates. As a comparison, TRPV1, a
      gene closely related to TRPA1, was found to be under strong purifying selection
      in all the species studied, with no difference in the strength of selection
      between pit-bearing snakes and non-pit snakes. This finding demonstrates that the
      adaptive evolution of TRPA1 specifically occurred within the pit-bearing snakes
      and may be related to the functional modification for detecting infrared
      radiation. In addition, by comparing the TRPA1 protein sequences, we identified
      11 amino acid sites that were diverged in pit-bearing snakes but conserved in non
      pit snakes and other vertebrates, 21 sites that were diverged only within pit
      vipers but conserved in the remaining snakes. These specific amino acid
      substitutions may be potentially functional important for infrared sensing.

PMID- 22163323
TI  - Unintended consequences of conservation actions: managing disease in complex
      ecosystems.
AB  - Infectious diseases are increasingly recognised to be a major threat to
      biodiversity. Disease management tools such as control of animal movements and
      vaccination can be used to mitigate the impact and spread of diseases in targeted
      species. They can reduce the risk of epidemics and in turn the risks of
      population decline and extinction. However, all species are embedded in
      communities and interactions between species can be complex, hence increasing the
      chance of survival of one species can have repercussions on the whole community
      structure. In this study, we use an example from the Serengeti ecosystem in
      Tanzania to explore how a vaccination campaign against Canine Distemper Virus
      (CDV) targeted at conserving the African lion (Panthera leo), could affect the
      viability of a coexisting threatened species, the cheetah (Acinonyx jubatus).
      Assuming that CDV plays a role in lion regulation, our results suggest that a
      vaccination programme, if successful, risks destabilising the simple two-species
      system considered, as simulations show that vaccination interventions could
      almost double the probability of extinction of an isolated cheetah population
      over the next 60 years. This work uses a simple example to illustrate how
      predictive modelling can be a useful tool in examining the consequence of
      vaccination interventions on non-target species. It also highlights the
      importance of carefully considering linkages between human-intervention, species
      viability and community structure when planning species-based conservation
      actions.

PMID- 22163324
TI  - Avian wing proportions and flight styles: first step towards predicting the
      flight modes of mesozoic birds.
AB  - We investigated the relationship between wing element proportions and flight mode
      in a dataset of living avian species to provide a framework for making basic
      estimates of the range of flight styles evolved by Mesozoic birds. Our results
      show that feather length (f(prim)) and total arm length (ta) (sum of the humerus,
      ulna and manus length) ratios differ significantly between four flight style
      groups defined and widely used for living birds and as a result are predictive
      for fossils. This was confirmed using multivariate ordination analyses, with four
      wing elements (humerus, ulna/radius, manus, primary feathers), that discriminate
      the four broad flight styles within living birds. Among the variables tested,
      manus length is closely correlated with wing size, yet is the poorest predictor
      for flight style, suggesting that the shape of the bones in the hand wing is most
      important in determining flight style. Wing bone thickness (shape) must vary with
      wing beat strength, with weaker forces requiring less bone. Finally, we show that
      by incorporating data from Mesozoic birds, multivariate ordination analyses can
      be used to predict the flight styles of fossils.

PMID- 22163325
TI  - Quantitative mass spectrometry analysis using PAcIFIC for the identification of
      plasma diagnostic biomarkers for abdominal aortic aneurysm.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by increased aortic
      vessel wall diameter (>1.5 times normal) and loss of parallelism. This disease is
      responsible for 1-4% mortality occurring on rupture in males older than 65 years.
      Due to its asymptomatic nature, proteomic techniques were used to search for
      diagnostic biomarkers that might allow surgical intervention under nonlife
      threatening conditions. METHODOLOGY/PRINCIPAL FINDINGS: Pooled human plasma
      samples of 17 AAA and 17 control patients were depleted of the most abundant
      proteins and compared using a data-independent shotgun proteomic strategy,
      Precursor Acquisition Independent From Ion Count (PAcIFIC), combined with
      spectral counting and isobaric tandem mass tags. Both quantitative methods
      collectively identified 80 proteins as statistically differentially abundant
      between AAA and control patients. Among differentially abundant proteins, a
      subgroup of 19 was selected according to Gene Ontology classification and
      implication in AAA for verification by Western blot (WB) in the same 34
      individual plasma samples that comprised the pools. From the 19 proteins, 12 were
      detected by WB. Five of them were verified to be differentially up-regulated in
      individual plasma of AAA patients: adiponectin, extracellular superoxide
      dismutase, protein AMBP, kallistatin and carboxypeptidase B2.
      CONCLUSIONS/SIGNIFICANCE: Plasma depletion of high abundance proteins combined
      with quantitative PAcIFIC analysis offered an efficient and sensitive tool for
      the screening of new potential biomarkers of AAA. However, WB analysis to verify
      the 19 PAcIFIC identified proteins of interest proved inconclusive save for five
      proteins. We discuss these five in terms of their potential relevance as
      biological markers for use in AAA screening of population at risk.

PMID- 22163326
TI  - MRI findings for frozen shoulder evaluation: is the thickness of the
      coracohumeral ligament a valuable diagnostic tool?
AB  - BACKGROUND: Recent studies have demonstrated that the coracohumeral ligament
      (CHL) is shortened and thickened in a frozen shoulder. We analyzed the rate in
      CHL visualization between patients with frozen shoulder and normal volunteers
      using Magnetic Resonance Imaging (MRI) to determine the CHL thickness in the
      patients with a frozen shoulder. METHODS AND FINDINGS: There were 72 shoulder
      joints in 72 patients (50 femles and 22 males with a mean age of 53.5 years) with
      clinical evidence and MR imaging evidence of frozen shoulder. These were
      prospectively analyzed to identify and measure the maximum thickness of the CHL.
      The control group, which included 120 shoulder joints in 60 normal volunteer
      individuals (30 females and 30 males with a mean age of 50.5 years) was also
      referred for MR imaging. A chi-square test was used to analyze the data of the
      rate of CHL visualization between the patients with frozen shoulder and the
      control group. A two-way ANOVA was used to analyze the mean maximal thickness of
      CHL. The CHL was visualized in 110 out of 120 shoulders in the control group
      (91.7%), and in 57 out of 72 shoulders for the frozen shoulder group (79.2%),
      there was significant difference, using a chi-square test (P<0.05). The CHL was
      not visualized in 10 out of 120 shoulders in the control group (8.3%), and 15 out
      of 72 shoulders in the frozen shoulder group (20.8%), there was a significant
      difference (P<0.05). The CHL thickness (3.99+/-1.68 mm) in the patients with
      frozen shoulder was significantly greater than that thickness (3.08+/-1.32 mm) in
      the control group, using a two-way ANOVA (P<0.001). The CHL thickness (3.52+/
      1.52 mm, n = 97) in the female shoulders was no significantly greater than that
      thickness (3.22+/-1.49 mm, n = 70) in the male shoulders, using a two-way ANOVA
      (P>0.05). CONCLUSIONS: MR Imaging is a satisfactory method for CHL depiction, and
      a thickened CHL is highly suggestive of frozen shoulder.

PMID- 22163327
TI  - Epithelial cells activate plasmacytoid dendritic cells improving their anti-HIV
      activity.
AB  - Plasmacytoid dendritic cells (pDCs) play a major role in anti-viral immunity by
      virtue of their ability to produce high amounts of type I interferons (IFNs) and
      a variety of inflammatory cytokines and chemokines in response to viral
      infections. Since recent studies have established that pDCs accumulate at the
      site of virus entry in the mucosa, here we analyzed whether epithelial cells were
      able to modulate the function of pDCs. We found that the epithelial cell lines HT
      29 and Caco-2, as well as a primary culture of human renal tubular epithelial
      cells (HRTEC), induced the phenotypic maturation of pDCs stimulating the
      production of inflammatory cytokines. By contrast, epithelial cells did not
      induce any change in the phenotype of conventional or myeloid DCs (cDCs) while
      significantly stimulated the production of the anti-inflammatory cytokine IL-10.
      Activation of pDCs by epithelial cells was prevented by Bafilomycin A1, an
      inhibitor of endosomal acidification as well as by the addition of RNase to the
      culture medium, suggesting the participation of endosomal TLRs. Interestingly,
      the cross-talk between both cell populations was shown to be associated to an
      increased expression of TLR7 and TLR9 by pDCs and the production of LL37 by
      epithelial cells, an antimicrobial peptide able to bind and transport
      extracellular nucleic acids into the endosomal compartments. Interestingly,
      epithelium-activated pDCs impaired the establishment of a productive HIV
      infection in two susceptible target cells through the stimulation of the
      production of type I IFNs, highlighting the anti-viral efficiency of this novel
      activation pathway.

PMID- 22163328
TI  - Mapping the organization of axis of motion selective features in human area MT
      using high-field fMRI.
AB  - Functional magnetic resonance imaging (fMRI) at high magnetic fields has made it
      possible to investigate the columnar organization of the human brain in vivo with
      high degrees of accuracy and sensitivity. Until now, these results have been
      limited to the organization principles of early visual cortex (V1). While the
      middle temporal area (MT) has been the first identified extra-striate visual area
      shown to exhibit a columnar organization in monkeys, evidence of MT's columnar
      response properties and topographic layout in humans has remained elusive.
      Research using various approaches suggests similar response properties as in
      monkeys but failed to provide direct evidence for direction or axis of motion
      selectivity in human area MT. By combining state of the art pulse sequence
      design, high spatial resolution in all three dimensions (0.8 mm isotropic),
      optimized coil design, ultrahigh field magnets (7 Tesla) and novel high
      resolution cortical grid sampling analysis tools, we provide the first direct
      evidence for large-scale axis of motion selective feature organization in human
      area MT closely matching predictions from topographic columnar-level simulations.

PMID- 22163329
TI  - Prescribing trends in bipolar disorder: cohort study in the United Kingdom THIN
      primary care database 1995-2009.
AB  - OBJECTIVES: To determine changes in prescribing patterns in primary care of
      antipsychotic and mood stabiliser medication in a representative sample of
      patients with bipolar disorder in the United Kingdom over a fifteen year period
      and association with socio-demographic factors. METHODS: We identified 4700
      patients in the Health Improvement Network (THIN) primary care database, who had
      received treatment for bipolar disorder between 1995 and 2009. The proportion of
      time for which each individual was prescribed a particular medication was
      studied, along with variation by sex, age and social depravation status
      (quintiles of Townsend scores). The number of drugs an individual was taking
      within a particular year was also examined. RESULTS: In 1995, 40.6% of patients
      with bipolar disorder were prescribed a psychotropic medication at least twice.
      By 2009 this had increased to 78.5% of patients. Valproate registered with the
      greatest increase in use (22.7%) followed by olanzapine (15.7%) and quetiapine
      (9.9%). There were differences by age and sex; with young (18-30 year old) women
      having the biggest increase in proportion of time on medication. There were no
      differences by social deprivation status. By 2009, 34.2% of women of childbearing
      age were treated with valproate. CONCLUSIONS: Lithium use overall remained
      relatively constant, whilst second generation antipsychotic and valproate use
      increased dramatically. Changes in prescribing practice preceded published trial
      evidence, especially with the use of second generation antipsychotics, perhaps
      with inferences being made from treatment of schizophrenia and use of first
      generation antipsychotics. Women of childbearing age were prescribed valproate
      frequently, against best advice.

PMID- 22163330
TI  - Aging worsens the effects of sleep deprivation on postural control.
AB  - Falls increase with age and cause significant injuries in the elderly. This study
      aimed to determine whether age modulates the interactions between sleep
      deprivation and postural control and to evaluate how attention influences these
      interactions in the elderly. Fifteen young (24+/-2.7 y.o.) and 15 older adults
      (64+/-3.2 y.o.) stood still on a force plate after a night of sleep and after
      total sleep deprivation. Center of pressure range and velocity were measured with
      eyes open and with eyes closed while participants performed an interference task,
      a control task, and no cognitive task. Sleep deprivation increased the antero
      posterior range of center of pressure in both age groups and center of pressure
      speed in older participants only. In elderly participants, the destabilizing
      effects of sleep deprivation were more pronounced with eyes closed. The
      interference task did not alter postural control beyond the destabilization
      induced by sleep loss in older subjects. It was concluded that sleep loss has
      greater destabilizing effects on postural control in older than in younger
      participants, and may therefore increase the risk of falls in the elderly.

PMID- 22163331
TI  - Protein 3D structure computed from evolutionary sequence variation.
AB  - The evolutionary trajectory of a protein through sequence space is constrained by
      its function. Collections of sequence homologs record the outcomes of millions of
      evolutionary experiments in which the protein evolves according to these
      constraints. Deciphering the evolutionary record held in these sequences and
      exploiting it for predictive and engineering purposes presents a formidable
      challenge. The potential benefit of solving this challenge is amplified by the
      advent of inexpensive high-throughput genomic sequencing.In this paper we ask
      whether we can infer evolutionary constraints from a set of sequence homologs of
      a protein. The challenge is to distinguish true co-evolution couplings from the
      noisy set of observed correlations. We address this challenge using a maximum
      entropy model of the protein sequence, constrained by the statistics of the
      multiple sequence alignment, to infer residue pair couplings. Surprisingly, we
      find that the strength of these inferred couplings is an excellent predictor of
      residue-residue proximity in folded structures. Indeed, the top-scoring residue
      couplings are sufficiently accurate and well-distributed to define the 3D protein
      fold with remarkable accuracy.We quantify this observation by computing, from
      sequence alone, all-atom 3D structures of fifteen test proteins from different
      fold classes, ranging in size from 50 to 260 residues, including a G-protein
      coupled receptor. These blinded inferences are de novo, i.e., they do not use
      homology modeling or sequence-similar fragments from known structures. The co
      evolution signals provide sufficient information to determine accurate 3D protein
      structure to 2.7-4.8 A C(alpha)-RMSD error relative to the observed structure,
      over at least two-thirds of the protein (method called EVfold, details at
      http://EVfold.org). This discovery provides insight into essential interactions
      constraining protein evolution and will facilitate a comprehensive survey of the
      universe of protein structures, new strategies in protein and drug design, and
      the identification of functional genetic variants in normal and disease genomes.

PMID- 22163332
TI  - Impact of the lectin chaperone calnexin on the stress response, virulence and
      proteolytic secretome of the fungal pathogen Aspergillus fumigatus.
AB  - Calnexin is a membrane-bound lectin chaperone in the endoplasmic reticulum (ER)
      that is part of a quality control system that promotes the accurate folding of
      glycoproteins entering the secretory pathway. We have previously shown that ER
      homeostasis is important for virulence of the human fungal pathogen Aspergillus
      fumigatus, but the contribution of calnexin has not been explored. Here, we
      determined the extent to which A. fumigatus relies on calnexin for growth under
      conditions of environmental stress and for virulence. The calnexin gene, clxA,
      was deleted from A. fumigatus and complemented by reconstitution with the wild
      type gene. Loss of clxA altered the proteolytic secretome of the fungus, but had
      no impact on growth rates in either minimal or complex media at 37 degrees C.
      However, the DeltaclxA mutant was growth impaired at temperatures above 42
      degrees C and was hypersensitive to acute ER stress caused by the reducing agent
      dithiothreitol. In contrast to wild type A. fumigatus, DeltaclxA hyphae were
      unable to grow when transferred to starvation medium. In addition, depleting the
      medium of cations by chelation prevented DeltaclxA from sustaining polarized
      hyphal growth, resulting in blunted hyphae with irregular morphology. Despite
      these abnormal stress responses, the DeltaclxA mutant remained virulent in two
      immunologically distinct models of invasive aspergillosis. These findings
      demonstrate that calnexin functions are needed for growth under conditions of
      thermal, ER and nutrient stress, but are dispensable for surviving the stresses
      encountered in the host environment.

PMID- 22163333
TI  - Viruses of fish: an overview of significant pathogens.
AB  - The growing global demand for seafood together with the limited capacity of the
      wild-capture sector to meet this demand has seen the aquaculture industry
      continue to grow around the world. A vast array of aquatic animal species is
      farmed in high density in freshwater, brackish and marine systems where they are
      exposed to new environments and potentially new diseases. On-farm stresses may
      compromise their ability to combat infection, and farming practices facilitate
      rapid transmission of disease. Viral pathogens, whether they have been
      established for decades or whether they are newly emerging as disease threats,
      are particularly challenging since there are few, if any, efficacious treatments,
      and the development of effective viral vaccines for delivery in aquatic systems
      remains elusive. Here, we review a few of the more significant viral pathogens of
      finfish, including aquabirnaviruses and infectious hematopoietic necrosis virus
      which have been known since the first half of the 20th century, and more recent
      viral pathogens, for example betanodaviruses, that have emerged as aquaculture
      has undergone a dramatic expansion in the past few decades.

PMID- 22163334
TI  - Baculovirus induced transcripts in hemocytes from the larvae of Heliothis
      virescens.
AB  - Using RNA-seq digital difference expression profiling methods, we have assessed
      the gene expression profiles of hemocytes harvested from Heliothis virescens that
      were challenged with Helicoverpa zea single nucleopolyhedrovirus (HzSNPV). A
      reference transcriptome of hemocyte-expressed transcripts was assembled from 202
      million 42-base tags by combining the sequence data of all samples, and the
      assembled sequences were then subject to BLASTx analysis to determine gene
      identities. We used the fully sequenced HzSNPV reference genome to align 477,264
      Illumina sequence tags from infected hemocytes in order to document expression of
      HzSNPV genes at early points during infection. A comparison of expression
      profiles of control insects to those lethally infected with HzSNPV revealed
      differential expression of key cellular stress response genes and genes involved
      in lipid metabolism. Transcriptional regulation of specific insect hormones in
      baculovirus-infected insects was also altered. A number of transcripts bearing
      homology to retroviral elements that were detected add to a growing body of
      evidence for extensive invasion of errantiviruses into the insect genome. Using
      this method, we completed the first and most comprehensive gene expression survey
      of both baculoviral infection and host immune defense in lepidopteran larvae.

PMID- 22163335
TI  - Antiviral immunity in amphibians.
AB  - Although a variety of virus species can infect amphibians, diseases caused by
      ranaviruses ([RVs]; Iridoviridae) have become prominent, and are a major concern
      for biodiversity, agriculture and international trade. The relatively recent and
      rapid increase in prevalence of RV infections, the wide range of host species
      infected by RVs, the variability in host resistance among population of the same
      species and among different developmental stages, all suggest an important
      involvement of the amphibian immune system. Nevertheless, the roles of the immune
      system in the etiology of viral diseases in amphibians are still poorly
      investigated. We review here the current knowledge of antiviral immunity in
      amphibians, focusing on model species such as the frog Xenopus and the salamander
      (Ambystoma tigrinum), and on recent progress in generating tools to better
      understand how host immune defenses control RV infections, pathogenicity, and
      transmission.

PMID- 22163336
TI  - Viruses infecting reptiles.
AB  - A large number of viruses have been described in many different reptiles. These
      viruses include arboviruses that primarily infect mammals or birds as well as
      viruses that are specific for reptiles. Interest in arboviruses infecting
      reptiles has mainly focused on the role reptiles may play in the epidemiology of
      these viruses, especially over winter. Interest in reptile specific viruses has
      concentrated on both their importance for reptile medicine as well as virus
      taxonomy and evolution. The impact of many viral infections on reptile health is
      not known. Koch's postulates have only been fulfilled for a limited number of
      reptilian viruses. As diagnostic testing becomes more sensitive, multiple
      infections with various viruses and other infectious agents are also being
      detected. In most cases the interactions between these different agents are not
      known. This review provides an update on viruses described in reptiles, the
      animal species in which they have been detected, and what is known about their
      taxonomic positions.

PMID- 22163337
TI  - Neutralizing antibody response to hepatitis C virus.
AB  - A critical first step in a "rational vaccine design" approach for hepatitis C
      virus (HCV) is to identify the most relevant mechanisms of immune protection.
      Emerging evidence provides support for a protective role of virus neutralizing
      antibodies, and the ability of the B cell response to modify the course of acute
      HCV infection. This has been made possible by the development of in vitro cell
      culture models, based on HCV retroviral pseudotype particles expressing E1E2 and
      infectious cell culture-derived HCV virions, and small animal models that are
      robust tools in studies of antibody-mediated virus neutralization. This review is
      focused on the immunogenic determinants on the E2 glycoprotein mediating virus
      neutralization and the pathways in which the virus is able to escape from immune
      containment. Encouraging findings from recent studies provide support for the
      existence of broadly neutralization antibodies that are not associated with virus
      escape. The identification of conserved epitopes mediating virus neutralization
      that are not associated with virus escape will facilitate the design of a vaccine
      immunogen capable of eliciting broadly neutralizing antibodies against this
      highly diverse virus.

PMID- 22163338
TI  - Activation of LTRs from different human endogenous retrovirus (HERV) families by
      the HTLV-1 tax protein and T-cell activators.
AB  - Human endogenous retroviruses (HERVs) represent approximately 8% of our genome.
      HERVs influence cellular gene expression and contribute to normal physiological
      processes such as cellular differentiation and morphogenesis. HERVs have also
      been associated with certain pathological conditions, including cancer and
      neurodegenerative diseases. As HTLV-1 causes adult T-cell leukemia and HTLV-1
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has been shown
      to modulate host gene expression mainly through the expression of the powerful
      Tax transactivator, herein we were interested in looking at the potential
      modulation capacity of HTLV-1 Tax on HERV expression. In order to evaluate the
      promoter activity of different HERV LTRs, pHERV-LTR-luc constructs were co
      transfected in Jurkat T-cells with a Tax expression vector. Tax expression
      potently increased the LTR activity of HERV-W8 and HERV-H (MC16). In parallel,
      Jurkat cells were also stimulated with different T-cell-activating agents and
      HERV LTRs were observed to respond to different combination of Forskolin,
      bpV[pic] a protein tyrosine phosphatase inhibitor, and PMA. Transfection of
      expression vectors for different Tax mutants in Jurkat cells showed that several
      transcription factors including CREB appeared to be important for HERV-W8 LTR
      activation. Deletion mutants were derived from the HERV-W8 LTR and the region
      from -137 to -123 was found to be important for LTR response following Tax
      expression in Jurkat cells, while a different region was shown to be required in
      cells treated with activators. Our results thus demonstrated that HTLV-1 Tax
      activates several HERV LTRs. This raises the possibility that upregulated HERV
      expression could be involved in diseases associated with HTLV-1 infection.

PMID- 22163339
TI  - Herpesviruses that infect fish.
AB  - Herpesviruses are host specific pathogens that are widespread among vertebrates.
      Genome sequence data demonstrate that most herpesviruses of fish and amphibians
      are grouped together (family Alloherpesviridae) and are distantly related to
      herpesviruses of reptiles, birds and mammals (family Herpesviridae). Yet, many of
      the biological processes of members of the order Herpesvirales are similar. Among
      the conserved characteristics are the virion structure, replication process, the
      ability to establish long term latency and the manipulation of the host immune
      response. Many of the similar processes may be due to convergent evolution. This
      overview of identified herpesviruses of fish discusses the diseases that
      alloherpesviruses cause, the biology of these viruses and the host-pathogen
      interactions. Much of our knowledge on the biology of Alloherpesvirdae is derived
      from research with two species: Ictalurid herpesvirus 1 (channel catfish virus)
      and Cyprinid herpesvirus 3 (koi herpesvirus).

PMID- 22163341
TI  - Biology and genomics of viruses within the genus Gammabaculovirus.
AB  - Hymenoptera is a very large and ancient insect order encompassing bees, wasps,
      ants and sawflies. Fossil records indicate that they existed over 200 million
      years ago and about 100 million years before the appearance of Lepidoptera.
      Sawflies have been major pests in many parts of the world and some have caused
      serious forest defoliation in North America. All baculoviruses isolated from
      sawflies are of the single nucleocapsids phenotype and appear to replicate in
      midgut cells only. This group of viruses has been shown to be excellent pest
      control agents and three have been registered in Canada and Britain for this
      purpose. Sawfly baculoviruses contain the smallest genome of all baculoviruses
      sequenced so far. Gene orders among sequenced sawfly baculoviruses are co-linear
      but this is not shared with the genomes of lepidopteran baculoviruses. One
      distinguishing feature among all sequenced sawfly viruses is the lack of a gene
      encoding a membrane fusion protein, which brought into question the role of the
      budded virus phenotype in Gammabaculovirus biology.

PMID- 22163342
TI  - N-terminally myristoylated feline foamy virus Gag allows Env-independent budding
      of sub-viral particles.
AB  - Foamy viruses (FVs) are distinct retroviruses classified as Spumaretrovirinae in
      contrast to the other retroviruses, the Orthoretrovirinae. As a unique feature of
      FVs, Gag is not sufficient for sub-viral particle (SVP) release. In primate and
      feline FVs (PFV and FFV), particle budding completely depends on the cognate FV
      Env glycoproteins. It was recently shown that an artificially added N-terminal
      Gag myristoylation signal (myr-signal) overcomes this restriction in PFV inducing
      an Orthoretrovirus-like budding phenotype. Here we show that engineered,
      heterologous N-terminal myr-signals also induce budding of the distantly related
      FFV Gag. The budding efficiency depends on the myr-signal and its location
      relative to the N-terminus of Gag. When the first nine amino acid residues of FFV
      Gag were replaced by known myr-signals, the budding efficiency as determined by
      the detection of extracellular SVPs was low. In contrast, adding myr-signals to
      the intact N-terminus of FFV Gag resulted in a more efficient SVP release.
      Importantly, budding of myr-Gag proteins was sensitive towards inhibition of
      cellular N-myristoyltransferases. As expected, the addition or insertion of myr
      signals that allowed Env-independent budding of FFV SVPs also retargeted Gag to
      plasma membrane-proximal sites and other intracellular membrane compartments. The
      data confirm that membrane-targeted FV Gag has the capacity of SVP formation.

PMID- 22163340
TI  - The molecular biology of feline immunodeficiency virus (FIV).
AB  - Feline immunodeficiency virus (FIV) is widespread in feline populations and
      causes an AIDS-like illness in domestic cats. It is highly prevalent in several
      endangered feline species. In domestic cats FIV infection is a valuable small
      animal model for HIV infection. In recent years there has been sa significant
      increase in interest in FIV, in part to exploit this, but also because of the
      potential it has as a human gene therapy vector. Though much less studied than
      HIV there are many parallels in the replication of the two viruses, but also
      important differences and, despite their likely common origin, the viruses have
      in some cases used alternative strategies to overcome similar problems. Recent
      advances in understanding the structure and function of FIV RNA and proteins and
      their interactions has enhanced our knowledge of FIV replication significantly,
      however, there are still many gaps. This review summarizes our current knowledge
      of FIV molecular biology and its similarities with, and differences from, other
      lentiviruses.

PMID- 22163343
TI  - Hepatitis C virus assembly imaging.
AB  - Hepatitis C Virus (HCV) assembly process is the least understood step in the
      virus life cycle. The functional data revealed by forward and reverse genetics
      indicated that both structural and non-structural proteins are involved in the
      assembly process. Using confocal and electron microscopy different groups
      determined the subcellular localization of different viral proteins and they
      identified the lipid droplets (LDs) as the potential viral assembly site. Here,
      we aim to review the mechanisms that govern the viral proteins recruitment to LDs
      and discuss the current model of HCV assembly process. Based on previous
      examples, this review will also discuss advanced imaging techniques as potential
      means to extend our present knowledge of HCV assembly process.

PMID- 22163344
TI  - Viral determinants of HIV-1 macrophage tropism.
AB  - Macrophages are important target cells for HIV-1 infection that play significant
      roles in the maintenance of viral reservoirs and other aspects of pathogenesis.
      Understanding the determinants of HIV-1 tropism for macrophages will inform HIV-1
      control and eradication strategies. Tropism for macrophages is both qualitative
      (infection or not) and quantitative (replication capacity). For example many R5
      HIV-1 isolates cannot infect macrophages, but for those that can the macrophage
      replication capacity can vary by up to 1000-fold. Some X4 viruses are also
      capable of replication in macrophages, indicating that cellular tropism is
      partially independent of co-receptor preference. Preliminary data obtained with a
      small number of transmitted/founder viruses indicate inefficient macrophage
      infection, whereas isolates from later in disease are more frequently tropic for
      macrophages. Thus tropism may evolve over time, and more macrophage tropic
      viruses may be implicated in the pathogenesis of advanced HIV-1 infection.
      Compartmentalization of macrophage-tropic brain-derived envelope glycoproteins
      (Envs), and non-macrophage tropic non-neural tissue-derived Envs points to
      adaptation of HIV-1 quasi-species in distinct tissue microenvironments. Mutations
      within and adjacent to the Env-CD4 binding site have been identified that
      determine macrophage tropism at the entry level, but post-entry molecular
      determinants of macrophage replication capacity involving HIV-1 accessory
      proteins need further definition.

PMID- 22163346
TI  - Complete sequence, analysis and organization of the Orgyia leucostigma
      nucleopolyhedrovirus genome.
AB  - The complete genome of the Orgyia leucostigma nucleopolyhedrovirus (OrleNPV)
      isolated from the whitemarked tussock moth (Orgyia leucostigma, Lymantridae:
      Lepidoptera) was sequenced, analyzed, and compared to other baculovirus genomes.
      The size of the OrleNPV genome was 156,179 base pairs (bp) and had a G+C content
      of 39%. The genome encoded 135 putative open reading frames (ORFs), which
      occupied 79% of the entire genome sequence. Three inhibitor of apoptosis (ORFs
      16, 43 and 63), and five baculovirus repeated ORFs (bro-a through bro-e) were
      interspersed in the OrleNPV genome. In addition to six direct repeat (drs), a
      common feature shared among most baculoviruses, OrleNPV genome contained three
      homologous regions (hrs) that are located in the latter half of the genome. The
      presence of an F-protein homologue and the results from phylogenetic analyses
      placed OrleNPV in the genus Alphabaculovirus, group II. Overall, OrleNPV appears
      to be most closely related to group II alphabaculoviruses Ectropis obliqua
      (EcobNPV), Apocheima cinerarium (ApciNPV), Euproctis pseudoconspersa (EupsNPV),
      and Clanis bilineata (ClbiNPV).

PMID- 22163345
TI  - Hepatitis C virus evasion mechanisms from neutralizing antibodies.
AB  - Hepatitis C virus (HCV) represents a major public health problem, affecting 3% of
      the world's population. The majority of infected individuals develop chronic
      hepatitis, which can progress to cirrhosis and hepatocellular carcinoma. To date,
      a vaccine is not available and current therapy is limited by resistance, adverse
      effects and high costs. Although it is very well established that cell-mediated
      immunity is necessary for viral clearance, the importance of host antibodies in
      clearing HCV infection is being increasingly recognized. Indeed, recent studies
      indicate that neutralizing antibodies are induced in the early phase of infection
      by patients who subsequently clear viral infection. Conversely, patients who do
      not clear the virus develop high titers of neutralizing antibodies during the
      chronic stage. Surprisingly, these antibodies are not able to control HCV
      infection. HCV has therefore developed mechanisms to evade immune elimination,
      allowing it to persist in the majority of infected individuals. A detailed
      understanding of the mechanisms by which the virus escapes immune surveillance is
      therefore necessary if novel preventive and therapeutic treatments have to be
      designed. This review summarizes the current knowledge of the mechanisms used by
      HCV to evade host neutralizing antibodies.

PMID- 22163347
TI  - Stress granules in the viral replication cycle.
AB  - As intracellular parasites, viruses require a host cell in order to replicate.
      However, they face a series of cellular responses against infection. One of these
      responses is the activation of the double-stranded RNA (dsRNA)-activated protein
      kinase R (PKR). PKR phosphorylates the alpha subunit of eukaryotic translation
      initiation factor 2 (eIF2alpha), which in turn results in global protein
      synthesis inhibition and formation of stress granules (SGs). Recent studies have
      shown that SGs can interfere with the replicative cycle of certain viruses. This
      review addresses how viruses have evolved different control strategies at the SG
      level to ensure an efficient replication cycle during the cellular stress
      response triggered by the viral infection.

PMID- 22163350
TI  - Regulation of wound-responsive calcium-dependent protein kinase from maize
      (ZmCPK11) by phosphatidic acid.
AB  - In plant cells, phospholipids are not only membrane components but also act as
      second messengers interacting with various proteins and regulating diverse
      cellular processes, including stress signal transduction. Here, we report studies
      on the effects of various phospholipids on the activity and expression of maize
      wound-responsive calcium-dependent protein kinase (ZmCPK11). Our results revealed
      that in leaves treated with n-butanol, a potent inhibitor of phosphatidic acid
      (PA) synthesis catalyzed by phospholipase D, a significant decrease of ZmCPK11
      activity was observed, indicating contribution of PA in the kinase activation.
      Using lipid binding assays, we demonstrate that among various phospholipids only
      saturated acyl species (16:0 and 18:0) of phosphatidic acid are able to bind to
      ZmCPK11. Saturated acyl species of PA are also able to stimulate phosphorylation
      of exogenous substrates by ZmCPK11 and autophosphorylation of the kinase. The
      level of ZmCPK11 autophosphorylation is correlated with its enzymatic activity.
      RT-PCR analysis showed that transcript level of ZmCPK11 in maize leaves increased
      in response to PA treatment. The influence of PA on the activity and transcript
      level of ZmCPK11 suggests an involvement of this kinase in a PA-mediated wound
      signal transduction pathway.

PMID- 22163351
TI  - Proteomic analysis of plasma profiles in children with recurrent bone fractures.
AB  - The aim of the study is proteomic analysis of the plasma profile in children with
      recurrent bone fractures. The study involved 16 children: 6 patients with
      recurrent low-energy fractures and normal bone mass and 10 with osteogenesis
      imperfecta. In the analysis of the protein profile, the two-dimensional protein
      electrophoresis was used (Ettan DALT II, Amersham Bioscience). The images of
      protein gels were compared with controls. The protein spots with changed
      expression were cut from the gel and the amino acid sequence was analyzed with
      the mass spectrometry method (Q-Tof Premier(TM) API MASS SPECTROMETR, Waters) for
      protein identification. The most prevalent protein with changed expression, with
      respect to controls, was haptoglobin observed in 6 patients with a severe form of
      osteogenesis imperfecta. Increased haptoglobin concentration in these patients
      was confirmed by the ELISA method. Peptides corresponding to alpha-1 acid
      glycoprotein and serum amyloid P-component, apolipoprotein A-I, and transthyretin
      were detected in one, two and three children, respectively. CONCLUSIONS: 1) The
      results show increased haptoglobin which may be suggestive of an inflammatory
      component taking part in the course of osteogenesis imperfecta. 2) Further
      studies to explain the possible relationship of this protein with increased bone
      fragility are necessary.

PMID- 22163352
TI  - There's no substitute for a family physician.

PMID- 22163353
TI  - Inhalation therapy: help patients avoid these mistakes.

PMID- 22163349
TI  - Ecopathology of ranaviruses infecting amphibians.
AB  - Ranaviruses are capable of infecting amphibians from at least 14 families and
      over 70 individual species. Ranaviruses infect multiple cell types, often
      culminating in organ necrosis and massive hemorrhaging. Subclinical infections
      have been documented, although their role in ranavirus persistence and emergence
      remains unclear. Water is an effective transmission medium for ranaviruses, and
      survival outside the host may be for significant duration. In aquatic
      communities, amphibians, reptiles and fish may serve as reservoirs. Controlled
      studies have shown that susceptibility to ranavirus infection and disease varies
      among amphibian species and developmental stages, and likely is impacted by host
      pathogen coevolution, as well as, exogenous environmental factors. Field studies
      have demonstrated that the likelihood of epizootics is increased in areas of
      cattle grazing, where aquatic vegetation is sparse and water quality is poor.
      Translocation of infected amphibians through commercial trade (e.g., food, fish
      bait, pet industry) contributes to the spread of ranaviruses. Such introductions
      may be of particular concern, as several studies report that ranaviruses isolated
      from ranaculture, aquaculture, and bait facilities have greater virulence (i.e.,
      ability to cause disease) than wild-type isolates. Future investigations should
      focus on the genetic basis for pathogen virulence and host susceptibility,
      ecological and anthropogenic mechanisms contributing to emergence, and vaccine
      development for use in captive populations and species reintroduction programs.

PMID- 22163354
TI  - How best to address these common movement disorders.

PMID- 22163355
TI  - Detecting and treating delirium--key interventions you may be missing.

PMID- 22163348
TI  - The Lymantria dispar IPLB-Ld652Y cell line transcriptome comprises diverse virus
      associated transcripts.
AB  - The enhanced viral susceptibility of the gypsy moth (Lymantria dispar)-derived
      IPLB-Ld652Y cell line has made it a popular in vitro system for studying virus
      related phenomena in the Lepidoptera. Using both single-pass EST sequencing and
      454-based pyrosequencing, a transcriptomic library of 14,368 putatively unique
      transcripts (PUTs) was produced comprising 8,476,050 high-quality, informative
      bases. The gene content of the IPLB-Ld652Y transcriptome was broadly assessed via
      comparison with the NCBI non-redundant protein database, and more detailed
      functional annotation was inferred by comparison to the Swiss-Prot subset of
      UniProtKB. In addition to L. dispar cellular transcripts, a diverse array of both
      RNA and DNA virus-associated transcripts was identified within the dataset,
      suggestive of a high level of viral expression and activity in IPLB-Ld652Y cells.
      These sequence resources will provide a sound basis for developing testable
      experimental hypotheses by insect virologists, and suggest a number of avenues
      for potential research.

PMID- 22163356
TI  - CDC update on gonorrhea: expand treatment to limit resistance.

PMID- 22163357
TI  - PURLs: postprostatectomy incontinence? Here's help.

PMID- 22163358
TI  - PURLs: offer this contraceptive to breastfeeding new moms.

PMID- 22163359
TI  - Acute abdominal pain in an elderly patient.

PMID- 22163360
TI  - Clinical inquiry: What treatment is best for hypertrophic scars and keloids?

PMID- 22163361
TI  - Clinical inquiry: How can we minimize recurrent ankle sprains?

PMID- 22163362
TI  - Clinical inquiry: What should you tell pregnant women about exposure to
      parvovirus?

PMID- 22163363
TI  - Clinical inquiry: Should you test for H pylori in patients with nonulcer
      dyspepsia?

PMID- 22163364
TI  - Clinical inquiry: Ferning in amniotic fluid: is it a useful indicator of ruptured
      membranes?

PMID- 22163365
TI  - Diabetes and alcohol use: detecting at-risk drinking.

PMID- 22163366
TI  - Rapid and highly sensitive protein extraction via cobalt oxide nanoparticle-based
      liquid-liquid microextraction coupled with MALDI mass spectrometry.
AB  - A new approach for rapid and highly sensitive protein extraction using cobalt
      oxide nanoparticles modified with cetyltrimethylammonium (Co(3)O(4)/CTA(+) NP)
      using nanoparticle-based liquid-liquid microextraction (NP-LLME) coupled with
      matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been
      successfully demonstrated. For the first time, the metal oxide NPs
      (Co(3)O(4)/CTA(+) NP) prepared in the organic phase (toluene) have been
      successfully applied for the extraction and preconcentration of proteins from
      sample solutions and complex samples via electrostatic forces involved between
      the metal oxide NP and proteins. Lysozyme was used as the model protein to
      investigate the optimal extraction parameters of the current approach. The
      optimal conditions were obtained at pH > pI for 10 min of incubation time
      (extraction time) with 3% salt (NaCl) addition. The Co(3)O(4)/CTA(+) NP was
      successfully applied for the highly sensitive analysis of an array proteins such
      as insulin, chymotrypsinogen and lysozyme from aqueous solution, protein mixture
      and milk samples in nanoparticle-based liquid-phase microextraction coupled with
      MALDI-MS. The potentiality of the NP-LLME using Co(3)O(4)/CTA(+) NP for the
      extraction of proteins was also compared with other types of NP-liquid phase
      microextraction (LPME) methods. The current approach offers distinct advantages
      including rapidity, straightforwardness, high sensitivity for washing- and
      separation-free MALDI-MS analysis of proteins.

PMID- 22163367
TI  - MU-XRF analysis of glasses: a non-destructive utility for Cultural Heritage
      applications.
AB  - This paper presents a MU-XRF analytical approach for a non-destructive study of
      Cultural Heritage glass finds. This technique can be used for quantitative
      analysis of small volumes of solid samples, with a sensitivity that is superior
      to the electron microprobe but inferior to an ICP-MS system. An experimental set
      up with natural and synthetic glass standards is proposed here for the
      quantitative analyses of major and trace elements on glass objects which cannot
      be sampled such as small archaeological or historical artefacts from Cultural
      Heritage. The described method, performed by means of the commercial MU-XRF Eagle
      III-XPL, was applied to Islamic glass specimens of Sasanian production (III-VII
      century A.D.) previously analyzed by ICP-MS and SEM-EDS techniques (P. Mirti, M.
      Pace, M. Negro Ponzi and M. Aceto, Archaeometry, 2008, 50(3), 429-450; P. Mirti,
      M. Pace, M. Malandrino and M. Negro Ponzi, J. Archaeol. Sci., 36, 1061-1069; and
      M. Gulmini, M. Pace, G. Ivaldi, M. Negro Ponzi and P. Mirti, J. Non-Cryst.
      Solids, 2009, 355, 1613-1621) and coming from the archaeological site of Veh
      Ardasir in modern Iraq. Major elements (Na, Mg, Al, Si, K, Ca, Fe) of glass
      specimens show an accuracy better than 5%. Trace elements (Cr, Mn, Sr and Zr)
      display an accuracy better than 5% when the checked elements have a concentration
      >100 ppm by weight, whereas it is around 10% with a concentration <100 ppm by
      weight. MU-XRF is, therefore, a suitable elemental analysis technique for the non
      destructive study of small glass finds due to its relatively good accuracy,
      reproducibility and low detection limits (~tens ppm).

PMID- 22163368
TI  - Magnetic actuation of hair cells.
AB  - The bullfrog sacculus contains mechanically sensitive hair cells whose
      stereociliary bundles oscillate spontaneously when decoupled from the overlying
      membrane. Steady-state offsets on the resting position of a hair bundle can
      suppress or modulate this native motility. To probe the dynamics of spontaneous
      oscillation in the proximity of the critical point, we describe here a method for
      mechanical actuation that avoids loading the bundles or contributing to the
      viscous drag. Magnetite beads were attached to the tips of the stereocilia, and a
      magnetic probe was used to impose deflections. This technique allowed us to
      observe the transition from multi-mode to single-mode state in freely oscillating
      bundles, as well as the crossover from the oscillatory to the quiescent state.

PMID- 22163369
TI  - On the topological derivative due to kink of a crack with non-penetration. Anti
      plane model.
AB  - A topological derivative is defined, which is caused by kinking of a crack, thus,
      representing the topological change. Using variational methods, the anti-plane
      model of a solid subject to a non-penetration condition imposed at the kinked
      crack is considered. The objective function of the potential energy is expanded
      with respect to the diminishing branch of the incipient crack. The respective
      sensitivity analysis is provided by a Saint-Venant principle and a local
      decomposition of the solution of the variational problem in the Fourier series.

PMID- 22163370
TI  - THE OXYGEN DISSOCIATION CURVE OF HEMOGLOBIN: BRIDGING THE GAP BETWEEN
      BIOCHEMISTRY AND PHYSIOLOGY.

PMID- 22163371
TI  - Migrant Parents and the Psychological Well-Being of Left-Behind Children in
      Southeast Asia.
AB  - Several million children currently live in transnational families, yet little is
      known about impacts on their health. We investigated the psychological well-being
      of left-behind children in four Southeast Asian countries. Data were drawn from
      the CHAMPSEA study. Caregiver reports from the Strengths and Difficulties
      Questionnaire (SDQ) were used to examine differences among children under age 12
      by the migration status of their household (N = 3,876). We found no general
      pattern across the four study countries: Indonesia, the Philippines, Thailand,
      and Vietnam. Multivariate models showed that children of migrant fathers in
      Indonesia and Thailand are more likely to have poor psychological well-being,
      compared to children in nonmigrant households. This finding was not replicated
      for the Philippines or Vietnam. The paper concludes by arguing for more
      contextualized understandings.

PMID- 22163373
TI  - An interrupted Ugi reaction enables the preparation of substituted indoxyls and
      aminoindoles.
AB  - In a variation of the classical Ugi reaction, an acid promoted reaction between
      imines and isocyanides forms both 3-aminoindoles and substituted indoxyls. A
      recently reported triflyl phosphoramide is shown to be critical to obtain high
      yields under mild conditions.

PMID- 22163372
TI  - A case-study in the clinical epidemiology of psoriatic arthritis: multistate
      models and causal arguments.
AB  - In psoriatic arthritis, permanent joint damage characterizes disease progression
      and represents a major debilitating aspect of the disease. Understanding the
      process of joint damage will assist in the treatment and disease management of
      patients. Multistate models provide a means to examine patterns of disease, such
      as symmetric joint damage. Additionally, the link between damage and the dynamic
      course of disease activity (represented by joint swelling and stress pain) at
      both the individual joint level and otherwise can be represented within a
      correlated multistate model framework. Correlation is reflected through the use
      of random effects for progressive models and robust variance estimation for non
      progressive models. Such analyses, undertaken with data from a large psoriatic
      arthritis cohort, are discussed and the extent to which they permit causal
      reasoning is considered. For this, emphasis is given to the use of the Bradford
      Hill criteria for causation in observational studies and the concept of local
      (in)dependence to capture the dynamic nature of the relationships.

PMID- 22163374
TI  - The effects of race and racial priming on self-report of contamination anxiety.
AB  - African Americans show unusually high endorsement rates on self-report measures
      of contamination anxiety. The purpose of this study was to replicate this finding
      in a nationally representative sample and conduct a randomized experiment to
      determine the effect of salience of race as a causal factor. Black and White
      participants were given contamination items from two popular measures of
      obsessive-compulsive disorder, half prior to being primed about ethnic identity
      and half after being primed, via the administration of an ethnic identity
      measure. The experiment took the form of a 2 (Black and White participant) X 2
      (ethnicity salient and ethnicity non-salient) double-blind design, with ethnic
      saliency assigned at random by computer. Participants consisted of a
      geographically representative US sample of African Americans supplemented with a
      similar sample of European Americans (N=258). Black participants scored
      significantly higher than White participants on contamination scales.
      Participants from Southern states scored higher than those from other regions.
      Over-endorsements by Black participants were greater when awareness of ethnic and
      racial identification was increased. Clinical and research implications were
      discussed; these measures should be used with caution in African Americans.

PMID- 22163376
TI  - Redundancy of minimal weight expansions in Pisot bases.
AB  - Motivated by multiplication algorithms based on redundant number representations,
      we study representations of an integer n as a sum n=?kepsilonkUk, where the
      digits epsilonk are taken from a finite alphabet Sigma and (Uk)k is a linear
      recurrent sequence of Pisot type with U0=1. The most prominent example of a base
      sequence (Uk)k is the sequence of Fibonacci numbers. We prove that the
      representations of minimal weight ?k|epsilonk| are recognised by a finite
      automaton and obtain an asymptotic formula for the average number of
      representations of minimal weight. Furthermore, we relate the maximal number of
      representations of a given integer to the joint spectral radius of a certain set
      of matrices.

PMID- 22163377
TI  - The analysis of Range Quickselect and related problems.
AB  - Range Quickselect, a simple modification of the well-known Quickselect algorithm
      for selection, can be used to efficiently find an element with rank k in a given
      range [i..j], out of n given elements. We study basic cost measures of Range
      Quickselect by computing exact and asymptotic results for the expected number of
      passes, comparisons and data moves during the execution of this algorithm.The key
      element appearing in the analysis of Range Quickselect is a trivariate recurrence
      that we solve in full generality. The general solution of the recurrence proves
      to be very useful, as it allows us to tackle several related problems, besides
      the analysis that originally motivated us.In particular, we have been able to
      carry out a precise analysis of the expected number of moves of the pth element
      when selecting the jth smallest element with standard Quickselect, where we are
      able to give both exact and asymptotic results.Moreover, we can apply our general
      results to obtain exact and asymptotic results for several parameters in binary
      search trees, namely the expected number of common ancestors of the nodes with
      rank i and j, the expected size of the subtree rooted at the least common
      ancestor of the nodes with rank i and j, and the expected distance between the
      nodes of ranks i and j.

PMID- 22163375
TI  - The plausibility of a role for mercury in the etiology of autism: a cellular
      perspective.
AB  - Autism is defined by a behavioral set of stereotypic and repetitious behavioral
      patterns in combination with social and communication deficits. There is emerging
      evidence supporting the hypothesis that autism may result from a combination of
      genetic susceptibility and exposure to environmental toxins at critical moments
      in development. Mercury (Hg) is recognized as a ubiquitous environmental
      neurotoxin and there is mounting evidence linking it to neurodevelopmental
      disorders, including autism. Of course, the evidence is not derived from
      experimental trials with humans but rather from methods focusing on biomarkers of
      Hg damage, measurements of Hg exposure, epidemiological data, and animal studies.
      For ethical reasons, controlled Hg exposure in humans will never be conducted.
      Therefore, to properly evaluate the Hg-autism etiological hypothesis, it is
      essential to first establish the biological plausibility of the hypothesis. This
      review examines the plausibility of Hg as the primary etiological agent driving
      the cellular mechanisms by which Hg-induced neurotoxicity may result in the
      physiological attributes of autism. Key areas of focus include: (1) route and
      cellular mechanisms of Hg exposure in autism; (2) current research and examples
      of possible genetic variables that are linked to both Hg sensitivity and autism;
      (3) the role Hg may play as an environmental toxin fueling the oxidative stress
      found in autism; (4) role of mitochondrial dysfunction; and (5) possible role of
      Hg in abnormal neuroexcitory and excitotoxity that may play a role in the immune
      dysregulation found in autism. Future research directions that would assist in
      addressing the gaps in our knowledge are proposed.

PMID- 22163378
TI  - Using ontology databases for scalable query answering, inconsistency detection,
      and data integration.
AB  - An ontology database is a basic relational database management system that models
      an ontology plus its instances. To reason over the transitive closure of
      instances in the subsumption hierarchy, for example, an ontology database can
      either unfold views at query time or propagate assertions using triggers at load
      time. In this paper, we use existing benchmarks to evaluate our method-using
      triggers-and we demonstrate that by forward computing inferences, we not only
      improve query time, but the improvement appears to cost only more space (not
      time). However, we go on to show that the true penalties were simply opaque to
      the benchmark, i.e., the benchmark inadequately captures load-time costs. We have
      applied our methods to two case studies in biomedicine, using ontologies and data
      from genetics and neuroscience to illustrate two important applications: first,
      ontology databases answer ontology-based queries effectively; second, using
      triggers, ontology databases detect instance-based inconsistencies-something not
      possible using views. Finally, we demonstrate how to extend our methods to
      perform data integration across multiple, distributed ontology databases.

PMID- 22163380
TI  - Influence of impurities and deformation temperature on the saturation
      microstructure and ductility of HPT-deformed nickel.
AB  - Ni with different purities between 99.69 and 99.99 wt.% was deformed by high
      pressure torsion (HPT) to high strains, where no further refinement of the
      microstructure is observed. The HPT deformation temperature varied between -196
      and 400  degrees C. Both impurities and temperature significantly affect the
      lower limit of the grain size obtained by HPT. In the investigated samples,
      carbon was the most important impurity element in controlling the limit of grain
      refinement. The decrease in grain size due to an increase in the carbon content
      from 0.008 to 0.06 wt.% for HPT-deformed Ni samples at room temperature enhanced
      the ultimate tensile strength from 1000 to 1700 MPa. Surprisingly, the carbon
      content did not deteriorate the ductility, defined as the reduction in area,
      which is mainly limited by the total amount of impurities besides carbon.
      Furthermore, the deformation temperature dependency on ductility was not very
      pronounced and only visible for deformation temperatures above 200  degrees C.

PMID- 22163379
TI  - Ultrasound biomicroscopy in small animal research: applications in molecular and
      preclinical imaging.
AB  - Ultrasound biomicroscopy (UBM) is a noninvasive multimodality technique that
      allows high-resolution imaging in mice. It is affordable, widely available, and
      portable. When it is coupled to Doppler ultrasound with color and power Doppler,
      it can be used to quantify blood flow and to image microcirculation as well as
      the response of tumor blood supply to cancer therapy. Target contrast ultrasound
      combines ultrasound with novel molecular targeted contrast agent to assess
      biological processes at molecular level. UBM is useful to investigate the growth
      and differentiation of tumors as well as to detect early molecular expression of
      cancer-related biomarkers in vivo and to monitor the effects of cancer therapies.
      It can be also used to visualize the embryological development of mice in uterus
      or to examine their cardiovascular development. The availability of real-time
      imaging of mice anatomy allows performing aspiration procedures under ultrasound
      guidance as well as the microinjection of cells, viruses, or other agents into
      precise locations. This paper will describe some basic principles of high
      resolution imaging equipment, and the most important applications in molecular
      and preclinical imaging in small animal research.

PMID- 22163381
TI  - Improved classification of Orthosiphon stamineus by data fusion of electronic
      nose and tongue sensors.
AB  - An improved classification of Orthosiphon stamineus using a data fusion technique
      is presented. Five different commercial sources along with freshly prepared
      samples were discriminated using an electronic nose (e-nose) and an electronic
      tongue (e-tongue). Samples from the different commercial brands were evaluated by
      the e-tongue and then followed by the e-nose. Applying Principal Component
      Analysis (PCA) separately on the respective e-tongue and e-nose data, only five
      distinct groups were projected. However, by employing a low level data fusion
      technique, six distinct groupings were achieved. Hence, this technique can
      enhance the ability of PCA to analyze the complex samples of Orthosiphon
      stamineus. Linear Discriminant Analysis (LDA) was then used to further validate
      and classify the samples. It was found that the LDA performance was also improved
      when the responses from the e-nose and e-tongue were fused together.

PMID- 22163382
TI  - Metal-insulator-semiconductor photodetectors.
AB  - The major radiation of the sun can be roughly divided into three regions:
      ultraviolet, visible, and infrared light. Detection in these three regions is
      important to human beings. The metal-insulator-semiconductor photodetector, with
      a simpler process than the pn-junction photodetector and a lower dark current
      than the MSM photodetector, has been developed for light detection in these three
      regions. Ideal UV photodetectors with high UV-to-visible rejection ratio could be
      demonstrated with III-V metal-insulator-semiconductor UV photodetectors. The
      visible-light detection and near-infrared optical communications have been
      implemented with Si and Ge metal-insulator-semiconductor photodetectors. For mid-
      and long-wavelength infrared detection, metal-insulator-semiconductor SiGe/Si
      quantum dot infrared photodetectors have been developed, and the detection
      spectrum covers atmospheric transmission windows.

PMID- 22163383
TI  - Wireless Intelligent Sensors Management Application Protocol-WISMAP.
AB  - Although many recent studies have focused on the development of new applications
      for wireless sensor networks, less attention has been paid to knowledge-based
      sensor nodes. The objective of this work is the development in a real network of
      a new distributed system in which every sensor node can execute a set of
      applications, such as fuzzy ruled-base systems, measures, and actions. The sensor
      software is based on a multi-agent structure that is composed of three
      components: management, application control, and communication agents; a service
      interface, which provides applications the abstraction of sensor hardware and
      other components; and an application layer protocol. The results show the
      effectiveness of the communication protocol and that the proposed system is
      suitable for a wide range of applications. As real world applications, this work
      presents an example of a fuzzy rule-based system and a noise pollution monitoring
      application that obtains a fuzzy noise indicator.

PMID- 22163384
TI  - Manganese(III) porphyrin-based potentiometric sensors for diclofenac assay in
      pharmaceutical preparations.
AB  - Two manganese(III) porphyrins: manganese(III) tetraphenylporphyrin chloride and
      manganese(III)-tetrakis(3-hydroxyphenyl)porphyrin chloride were tested as
      ionophores for the construction of new diclofenac-selective electrodes. The
      electroactive material was incorporated either in PVC or a sol-gel matrix. The
      effect of different plasticizers and additives (anionic and cationic) on the
      potentiometric response was studied. The best results were obtained for the PVC
      membrane plasticized with dioctylphtalate and having sodium tetraphenylborate as
      a lipophilic anionic additive incorporated. The sensor response was linear in the
      concentration range 3 * 10(-6) - 1 * 10(-2) M with a slope of -59.7 mV/dec
      diclofenac, a detection limit of 1.5 * 10(-6) M and very good selectivity
      coefficients. It was used for the determination of diclofenac in pharmaceutical
      preparations, by direct potentiometry. The results were compared with those
      obtained by the HPLC reference method and a good agreement was found between the
      two methods.

PMID- 22163385
TI  - Stereo vision tracking of multiple objects in complex indoor environments.
AB  - This paper presents a novel system capable of solving the problem of tracking
      multiple targets in a crowded, complex and dynamic indoor environment, like those
      typical of mobile robot applications. The proposed solution is based on a stereo
      vision set in the acquisition step and a probabilistic algorithm in the obstacles
      position estimation process. The system obtains 3D position and speed information
      related to each object in the robot's environment; then it achieves a
      classification between building elements (ceiling, walls, columns and so on) and
      the rest of items in robot surroundings. All objects in robot surroundings, both
      dynamic and static, are considered to be obstacles but the structure of the
      environment itself. A combination of a Bayesian algorithm and a deterministic
      clustering process is used in order to obtain a multimodal representation of
      speed and position of detected obstacles. Performance of the final system has
      been tested against state of the art proposals; test results validate the
      authors' proposal. The designed algorithms and procedures provide a solution to
      those applications where similar multimodal data structures are found.

PMID- 22163386
TI  - A bankruptcy problem approach to load-shedding in multiagent-based microgrid
      operation.
AB  - A microgrid is composed of distributed power generation systems (DGs),
      distributed energy storage devices (DSs), and loads. To maintain a specific
      frequency in the islanded mode as an important requirement, the control of DGs'
      output and charge action of DSs are used in supply surplus conditions and load
      shedding and discharge action of DSs are used in supply shortage conditions.
      Recently, multiagent systems for autonomous microgrid operation have been
      studied. Especially, load-shedding, which is intentional reduction of electricity
      use, is a critical problem in islanded microgrid operation based on the
      multiagent system. Therefore, effective schemes for load-shedding are required.
      Meanwhile, the bankruptcy problem deals with dividing short resources among
      multiple agents. In order to solve the bankruptcy problem, division rules, such
      as the constrained equal awards rule (CEA), the constrained equal losses rule
      (CEL), and the random arrival rule (RA), have been used. In this paper, we
      approach load-shedding as a bankruptcy problem. We compare load-shedding results
      by above-mentioned rules in islanded microgrid operation based on wireless sensor
      network (WSN) as the communication link for an agent's interactions.

PMID- 22163387
TI  - Multitemporal observations of sugarcane by TerraSAR-X images.
AB  - The objective of this study is to investigate the potential of TerraSAR-X (X
      band) in monitoring sugarcane growth on Reunion Island (located in the Indian
      Ocean). Multi-temporal TerraSAR data acquired at various incidence angles (17
      degrees , 31 degrees , 37 degrees , 47 degrees , 58 degrees ) and polarizations
      (HH, HV, VV) were analyzed in order to study the behaviour of SAR (synthetic
      aperture radar) signal as a function of sugarcane height and NDVI (Normalized
      Difference Vegetation Index). The potential of TerraSAR for mapping the sugarcane
      harvest was also studied. Radar signal increased quickly with crop height until a
      threshold height, which depended on polarization and incidence angle. Beyond this
      threshold, the signal increased only slightly, remained constant, or even
      decreased. The threshold height is slightly higher with cross polarization and
      higher incidence angles (47 degrees  in comparison with 17 degrees  and 31
      degrees ). Results also showed that the co-polarizations channels (HH and VV)
      were well correlated. High correlation between SAR signal and NDVI calculated
      from SPOT-4/5 images was observed. TerraSAR data showed that after strong rains
      the soil contribution to the backscattering of sugarcane fields can be important
      for canes with heights of terminal visible dewlap (htvd) less than 50 cm (total
      cane heights around 155 cm). This increase in radar signal after strong rains
      could involve an ambiguity between young and mature canes. Indeed, the radar
      signal on TerraSAR images acquired in wet soil conditions could be of the same
      order for fields recently harvested and mature sugarcane fields, making difficult
      the detection of cuts. Finally, TerraSAR data at high spatial resolution were
      shown to be useful for monitoring sugarcane harvest when the fields are of small
      size or when the cut is spread out in time. The comparison between incidence
      angles of 17 degrees , 37 degrees  and 58 degrees  shows that 37 degrees  is more
      suitable to monitor the sugarcane harvest. The cut is easily detectable on
      TerraSAR images for data acquired less than two or three months after the cut.
      The radar signal decreases about 5dB for images acquired some days after the cut
      and 3 dB for data acquired two month after the cut (VV-37 degrees ). The
      difference in radar signal becomes negligible (<1 dB) between harvested fields
      and mature canes for sugarcane harvested since three months or more.

PMID- 22163388
TI  - ZERO: probabilistic routing for deploy and forget Wireless Sensor Networks.
AB  - As Wireless Sensor Networks are being adopted by industry and agriculture for
      large-scale and unattended deployments, the need for reliable and energy
      conservative protocols become critical. Physical and Link layer efforts for
      energy conservation are not mostly considered by routing protocols that put their
      efforts on maintaining reliability and throughput. Gradient-based routing
      protocols route data through most reliable links aiming to ensure 99% packet
      delivery. However, they suffer from the so-called "hot spot" problem. Most
      reliable routes waste their energy fast, thus partitioning the network and
      reducing the area monitored. To cope with this "hot spot" problem we propose ZERO
      a combined approach at Network and Link layers to increase network lifespan while
      conserving reliability levels by means of probabilistic load balancing
      techniques.

PMID- 22163389
TI  - A smart checkpointing scheme for improving the reliability of clustering routing
      protocols.
AB  - In wireless sensor networks, system architectures and applications are designed
      to consider both resource constraints and scalability, because such networks are
      composed of numerous sensor nodes with various sensors and actuators, small
      memories, low-power microprocessors, radio modules, and batteries. Clustering
      routing protocols based on data aggregation schemes aimed at minimizing packet
      numbers have been proposed to meet these requirements. In clustering routing
      protocols, the cluster head plays an important role. The cluster head collects
      data from its member nodes and aggregates the collected data. To improve
      reliability and reduce recovery latency, we propose a checkpointing scheme for
      the cluster head. In the proposed scheme, backup nodes monitor and checkpoint the
      current state of the cluster head periodically. We also derive the checkpointing
      interval that maximizes reliability while using the same amount of energy
      consumed by clustering routing protocols that operate without checkpointing.
      Experimental comparisons with existing non-checkpointing schemes show that our
      scheme reduces both energy consumption and recovery latency.

PMID- 22163390
TI  - Optical sensing properties of dithiocarbamate-functionalized microspheres, using
      a polyvinylpyridine-polyvinylbenzyl chloride copolymer.
AB  - In this study, a new modified optical chemical sensor based on swellable polymer
      microspheres is developed using a 5% copolymer of polyvinylpyridine-polyvinyl
      benzyl chloride microspheres functionalized as the corresponding dithiocarbamate.
      This sensor demonstrated significant enhancements in sensitivity, dynamic range
      and response time. These improvements are related to the presence of pyridine in
      the polymer backbone, which is believed to increase the space between the groups,
      thus decreasing steric hindrance, and hence increasing substitution of the
      dithiocarbamate group. The hydrophilicity of pyridine also allows free movement
      of the solvent and analyte to and from the inside of the microspheres. These
      dithiocarbamate-derivatized polymer microspheres were embedded in a hydrogel
      matrix of polyvinylalcohol cross-linked with glutaraldehyde. This sensor
      responded selectively to Hg(2+) solutions of different concentrations (1 * 10(-5)
      M to 0.1 M). The observed turbidity measured as absorbance varied between 1.05
      and 1.75 units at a wavelength of 700 nm. The response is based on the
      interaction between the metal cations with the negative charges of the
      deprotonated dithiocarbamate functional group, which led to neutratization of the
      charges and thus to polymer shrinking. As a result, an increase in the turbidity
      of the sensing element due to a change in the refractive index between the
      hydrogel and the polymer microspheres occurred. The changes in the turbidity of
      the sensing element were measured as absorbance using a conventional
      spectrophotometer.

PMID- 22163391
TI  - A monitoring system for vegetable greenhouses based on a wireless sensor network.
AB  - A wireless sensor network-based automatic monitoring system is designed for
      monitoring the life conditions of greenhouse vegetables. The complete system
      architecture includes a group of sensor nodes, a base station, and an internet
      data center. For the design of wireless sensor node, the JN5139 micro-processor
      is adopted as the core component and the Zigbee protocol is used for wireless
      communication between nodes. With an ARM7 microprocessor and embedded ZKOS
      operating system, a proprietary gateway node is developed to achieve data influx,
      screen display, system configuration and GPRS based remote data forwarding.
      Through a Client/Server mode the management software for remote data center
      achieves real-time data distribution and time-series analysis. Besides, a GSM
      short-message-based interface is developed for sending real-time environmental
      measurements, and for alarming when a measurement is beyond some pre-defined
      threshold. The whole system has been tested for over one year and satisfactory
      results have been observed, which indicate that this system is very useful for
      greenhouse environment monitoring.

PMID- 22163392
TI  - Study and evaluation of a PCB-MEMS liquid microflow sensor.
AB  - This paper presents the evaluation of a miniature liquid microflow sensor,
      directly integrated on a PCB. The sensor operation is based on the convective
      heat transfer principle. The heating and sensing elements are thin Pt resistors
      which are in direct electrical contact with the external copper tracks of the
      printed circuit board. Due to the low thermal conductivity of the substrate
      material, a high degree of thermal isolation is obtained which improves the
      operating characteristics of the device. The sensor is able to operate under both
      the hot-wire and the calorimetric principle. In order to fully exploit the
      temperature distribution in the flowing liquid, multiple sensing elements are
      positioned in various distances from the heater. A special housing was developed
      which allowed implementation of the sensor into tubes of various cross sectional
      areas. The sensor sensitivity and measurement range as a function of the sensing
      element distance were quantified. A minimum resolution of 3 MUL/min and a
      measurement flow range up to 500 MUL/min were achieved.

PMID- 22163394
TI  - Experimental method for characterizing electrical steel sheets in the normal
      direction.
AB  - This paper proposes an experimental method to characterise magnetic laminations
      in the direction normal to the sheet plane. The principle, which is based on a
      static excitation to avoid planar eddy currents, is explained and specific test
      benches are proposed. Measurements of the flux density are made with a sensor
      moving in and out of an air-gap. A simple analytical model is derived in order to
      determine the permeability in the normal direction. The experimental results for
      grain oriented steel sheets are presented and a comparison is provided with
      values obtained from literature.

PMID- 22163393
TI  - Wearable systems for monitoring mobility-related activities in chronic disease: a
      systematic review.
AB  - The use of wearable motion sensing technology offers important advantages over
      conventional methods for obtaining measures of physical activity and/or physical
      functioning in individuals with chronic diseases. This review aims to identify
      the actual state of applying wearable systems for monitoring mobility-related
      activity in individuals with chronic disease conditions. In this review we focus
      on technologies and applications, feasibility and adherence aspects, and clinical
      relevance of wearable motion sensing technology. PubMed (Medline since 1990),
      PEdro, and reference lists of all relevant articles were searched. Two authors
      independently reviewed randomised trials systematically. The quality of selected
      articles was scored and study results were summarised and discussed. 163
      abstracts were considered. After application of inclusion criteria and full text
      reading, 25 articles were taken into account in a full text review. Twelve of
      these papers evaluated walking with pedometers, seven used uniaxial
      accelerometers to assess physical activity, six used multiaxial accelerometers,
      and two papers used a combination approach of a pedometer and a multiaxial
      accelerometer for obtaining overall activity and energy expenditure measures.
      Seven studies mentioned feasibility and/or adherence aspects. The number of
      studies that use movement sensors for monitoring of activity patterns in chronic
      disease (postural transitions, time spent in certain positions or activities) is
      nonexistent on the RCT level of study design. Although feasible methods for
      monitoring human mobility are available, evidence-based clinical applications of
      these methods in individuals with chronic diseases are in need of further
      development.

PMID- 22163395
TI  - A data compression algorithm for wireless sensor networks based on an optimal
      order estimation model and distributed coding.
AB  - In many wireless sensor network applications, the possibility of exceptions
      occurring is relatively small, so in a normal situation, data obtained at
      sequential time points by the same node are time correlated, while, spatial
      correlation may exist in data obtained at the same time by adjacent nodes. A
      great deal of node energy will be wasted if data which include time and space
      correlation is transmitted. Therefore, this paper proposes a data compression
      algorithm for wireless sensor networks based on optimal order estimation and
      distributed coding. Sinks can obtain correlation parameters based on optimal
      order estimation by exploring time and space redundancy included in data which is
      obtained by sensors. Then the sink restores all data based on time and space
      correlation parameters and only a little necessary data needs to be transmitted
      by nodes. Because of the decrease of redundancy, the average energy cost per node
      will be reduced and the life of the wireless sensor network will obviously be
      extended as a result.

PMID- 22163396
TI  - A sensor network data compression algorithm based on suboptimal clustering and
      virtual landmark routing within clusters.
AB  - A kind of data compression algorithm for sensor networks based on suboptimal
      clustering and virtual landmark routing within clusters is proposed in this
      paper. Firstly, temporal redundancy existing in data obtained by the same node in
      sequential instants can be eliminated. Then sensor networks nodes will be
      clustered. Virtual node landmarks in clusters can be established based on cluster
      heads. Routing in clusters can be realized by combining a greedy algorithm and a
      flooding algorithm. Thirdly, a global structure tree based on cluster heads will
      be established. During the course of data transmissions from nodes to cluster
      heads and from cluster heads to sink, the spatial redundancy existing in the data
      will be eliminated. Only part of the raw data needs to be transmitted from nodes
      to sink, and all raw data can be recovered in the sink based on a compression
      code and part of the raw data. Consequently, node energy can be saved, largely
      because transmission of redundant data can be avoided. As a result the overall
      performance of the sensor network can obviously be improved.

PMID- 22163397
TI  - Electro-quasistatic analysis of an electrostatic induction micromotor using the
      cell method.
AB  - An electro-quasistatic analysis of an induction micromotor has been realized by
      using the Cell Method. We employed the direct Finite Formulation (FF) of the
      electromagnetic laws, hence, avoiding a further discretization. The Cell Method
      (CM) is used for solving the field equations at the entire domain (2D space) of
      the micromotor. We have reformulated the field laws in a direct FF and analyzed
      physical quantities to make explicit the relationship between magnitudes and
      laws. We applied a primal-dual barycentric discretization of the 2D space. The
      electric potential has been calculated on each node of the primal mesh using CM.
      For verification purpose, an analytical electric potential equation is introduced
      as reference. In frequency domain, results demonstrate the error in calculating
      potential quantity is neglected (<30/00). In time domain, the potential value in
      transient state tends to the steady state value.

PMID- 22163398
TI  - Characterization of a photodiode coupled with a Si nanowire-FET on a plastic
      substrate.
AB  - In this study, a laterally coupled device composed of a photodiode and a Si
      nanowires-field-effect transistor (NWs-FET) is constructed on a plastic substrate
      and the coupled device is characterized. The photodiode is made of p-type Si NWs
      and an n-type ZnO film. The Si NWs-FET is connected electrically to the
      photodiode in order to enhance the latter's photocurrent efficiency by adjusting
      the gate voltage of the FET. When the FET is switched on by biasing a gate
      voltage of -9 V, the photocurrent efficiency of the photodiode is three times
      higher than that when the FET is switched off by biasing a gate voltage of 0 V.

PMID- 22163399
TI  - Electronic nose breathprints are independent of acute changes in airway caliber
      in asthma.
AB  - Molecular profiling of exhaled volatile organic compounds (VOC) by electronic
      nose technology provides breathprints that discriminate between patients with
      different inflammatory airway diseases, such as asthma and COPD. However, it is
      unknown whether this is determined by differences in airway caliber. We
      hypothesized that breathprints obtained by electronic nose are independent of
      acute changes in airway caliber in asthma. Ten patients with stable asthma
      underwent methacholine provocation (Visit 1) and sham challenge with isotonic
      saline (Visit 2). At Visit 1, exhaled air was repetitively collected pre
      challenge, after reaching the provocative concentration (PC(20)) causing 20% fall
      in forced expiratory volume in 1 second (FEV(1)) and after subsequent salbutamol
      inhalation. At Visit 2, breath was collected pre-challenge, post-saline and post
      salbutamol. At each occasion, an expiratory vital capacity was collected after 5
      min of tidal breathing through an inspiratory VOC-filter in a Tedlar bag and
      sampled by electronic nose (Cyranose 320). Breathprints were analyzed with
      principal component analysis and individual factors were compared with mixed
      model analysis followed by pairwise comparisons. Inhalation of methacholine led
      to a 30.8 +/- 3.3% fall in FEV(1) and was followed by a significant change in
      breathprint (p = 0.04). Saline inhalation did not induce a significant change in
      FEV(1), but altered the breathprint (p = 0.01). However, the breathprint obtained
      after the methacholine provocation was not significantly different from that
      after saline challenge (p = 0.27). The molecular profile of exhaled air in
      patients with asthma is altered by nebulized aerosols, but is not affected by
      acute changes in airway caliber. Our data demonstrate that breathprints by
      electronic nose are not confounded by the level of airway obstruction.

PMID- 22163400
TI  - Column-parallel correlated multiple sampling circuits for CMOS image sensors and
      their noise reduction effects.
AB  - For low-noise complementary metal-oxide-semiconductor (CMOS) image sensors, the
      reduction of pixel source follower noises is becoming very important. Column
      parallel high-gain readout circuits are useful for low-noise CMOS image sensors.
      This paper presents column-parallel high-gain signal readout circuits, correlated
      multiple sampling (CMS) circuits and their noise reduction effects. In the CMS,
      the gain of the noise cancelling is controlled by the number of samplings. It has
      a similar effect to that of an amplified CDS for the thermal noise but is a
      little more effective for 1/f and RTS noises. Two types of the CMS with simple
      integration and folding integration are proposed. In the folding integration, the
      output signal swing is suppressed by a negative feedback using a comparator and
      one-bit D-to-A converter. The CMS circuit using the folding integration technique
      allows to realize a very low-noise level while maintaining a wide dynamic range.
      The noise reduction effects of their circuits have been investigated with a noise
      analysis and an implementation of a 1Mpixel pinned photodiode CMOS image sensor.
      Using 16 samplings, dynamic range of 59.4 dB and noise level of 1.9 e(-) for the
      simple integration CMS and 75 dB and 2.2 e(-) for the folding integration CMS,
      respectively, are obtained.

PMID- 22163401
TI  - A method for direct measurement of the first-order mass moments of human body
      segments.
AB  - We propose a simple and direct method for measuring the first-order mass moment
      of a human body segment. With the proposed method, the first-order mass moment of
      the body segment can be directly measured by using only one precision scale and
      one digital camera. In the dummy mass experiment, the relative standard
      uncertainty of a single set of measurements of the first-order mass moment is
      estimated to be 1.7%. The measured value will be useful as a reference for
      evaluating the uncertainty of the body segment inertial parameters (BSPs)
      estimated using an indirect method.

PMID- 22163402
TI  - A zero velocity detection algorithm using inertial sensors for pedestrian
      navigation systems.
AB  - In pedestrian navigation systems, the position of a pedestrian is computed using
      an inertial navigation algorithm. In the algorithm, the zero velocity updating
      plays an important role, where zero velocity intervals are detected and the
      velocity error is reset. To use the zero velocity updating, it is necessary to
      detect zero velocity intervals reliably. A new zero detection algorithm is
      proposed in the paper, where only one gyroscope value is used. A Markov model is
      constructed using segmentation of gyroscope outputs instead of using gyroscope
      outputs directly, which makes the zero velocity detection more reliable.

PMID- 22163403
TI  - Development of a portable electronic nose system for the detection and
      classification of fruity odors.
AB  - In this study, we have developed a prototype of a portable electronic nose (E
      Nose) comprising a sensor array of eight commercially available sensors, a data
      acquisition interface PCB, and a microprocessor. Verification software was
      developed to verify system functions. Experimental results indicate that the
      proposed system prototype is able to identify the fragrance of three fruits,
      namely lemon, banana, and litchi.

PMID- 22163404
TI  - Design of belief propagation based on FPGA for the multistereo CAFADIS camera.
AB  - In this paper we describe a fast, specialized hardware implementation of the
      belief propagation algorithm for the CAFADIS camera, a new plenoptic sensor
      patented by the University of La Laguna. This camera captures the lightfield of
      the scene and can be used to find out at which depth each pixel is in focus. The
      algorithm has been designed for FPGA devices using VHDL. We propose a parallel
      and pipeline architecture to implement the algorithm without external memory.
      Although the BRAM resources of the device increase considerably, we can maintain
      real-time restrictions by using extremely high-performance signal processing
      capability through parallelism and by accessing several memories simultaneously.
      The quantifying results with 16 bit precision have shown that performances are
      really close to the original Matlab programmed algorithm.

PMID- 22163405
TI  - The Rover Environmental Monitoring Station Ground Temperature Sensor: a pyrometer
      for measuring ground temperature on Mars.
AB  - We describe the parameters that drive the design and modeling of the Rover
      Environmental Monitoring Station (REMS) Ground Temperature Sensor (GTS), an
      instrument aboard NASA's Mars Science Laboratory, and report preliminary test
      results. REMS GTS is a lightweight, low-power, and low cost pyrometer for
      measuring the Martian surface kinematic temperature. The sensor's main feature is
      its innovative design, based on a simple mechanical structure with no moving
      parts. It includes an in-flight calibration system that permits sensor
      recalibration when sensor sensitivity has been degraded by deposition of dust
      over the optics. This paper provides the first results of a GTS engineering model
      working in a Martian-like, extreme environment.

PMID- 22163406
TI  - An intelligent architecture based on Field Programmable Gate Arrays designed to
      detect moving objects by using Principal Component Analysis.
AB  - This paper presents a complete implementation of the Principal Component Analysis
      (PCA) algorithm in Field Programmable Gate Array (FPGA) devices applied to high
      rate background segmentation of images. The classical sequential execution of
      different parts of the PCA algorithm has been parallelized. This parallelization
      has led to the specific development and implementation in hardware of the
      different stages of PCA, such as computation of the correlation matrix, matrix
      diagonalization using the Jacobi method and subspace projections of images. On
      the application side, the paper presents a motion detection algorithm, also
      entirely implemented on the FPGA, and based on the developed PCA core. This
      consists of dynamically thresholding the differences between the input image and
      the one obtained by expressing the input image using the PCA linear subspace
      previously obtained as a background model. The proposal achieves a high ratio of
      processed images (up to 120 frames per second) and high quality segmentation
      results, with a completely embedded and reliable hardware architecture based on
      commercial CMOS sensors and FPGA devices.

PMID- 22163407
TI  - Intelligent sensor positioning and orientation through constructive neural
      network-embedded INS/GPS integration algorithms.
AB  - Mobile mapping systems have been widely applied for acquiring spatial information
      in applications such as spatial information systems and 3D city models. Nowadays
      the most common technologies used for positioning and orientation of a mobile
      mapping system include a Global Positioning System (GPS) as the major positioning
      sensor and an Inertial Navigation System (INS) as the major orientation sensor.
      In the classical approach, the limitations of the Kalman Filter (KF) method and
      the overall price of multi-sensor systems have limited the popularization of most
      land-based mobile mapping applications. Although intelligent sensor positioning
      and orientation schemes consisting of Multi-layer Feed-forward Neural Networks
      (MFNNs), one of the most famous Artificial Neural Networks (ANNs), and
      KF/smoothers, have been proposed in order to enhance the performance of low cost
      Micro Electro Mechanical System (MEMS) INS/GPS integrated systems, the automation
      of the MFNN applied has not proven as easy as initially expected. Therefore, this
      study not only addresses the problems of insufficient automation in the
      conventional methodology that has been applied in MFNN-KF/smoother algorithms for
      INS/GPS integrated systems proposed in previous studies, but also exploits and
      analyzes the idea of developing alternative intelligent sensor positioning and
      orientation schemes that integrate various sensors in more automatic ways. The
      proposed schemes are implemented using one of the most famous constructive neural
      networks--the Cascade Correlation Neural Network (CCNNs)--to overcome the
      limitations of conventional techniques based on KF/smoother algorithms as well as
      previously developed MFNN-smoother schemes. The CCNNs applied also have the
      advantage of a more flexible topology compared to MFNNs. Based on the
      experimental data utilized the preliminary results presented in this article
      illustrate the effectiveness of the proposed schemes compared to smoother
      algorithms as well as the MFNN-smoother schemes.

PMID- 22163408
TI  - Optical oxygen sensors for applications in microfluidic cell culture.
AB  - The presence and concentration of oxygen in biological systems has a large impact
      on the behavior and viability of many types of cells, including the
      differentiation of stem cells or the growth of tumor cells. As a result, the
      integration of oxygen sensors within cell culture environments presents a
      powerful tool for quantifying the effects of oxygen concentrations on cell
      behavior, cell viability, and drug effectiveness. Because microfluidic cell
      culture environments are a promising alternative to traditional cell culture
      platforms, there is recent interest in integrating oxygen-sensing mechanisms with
      microfluidics for cell culture applications. Optical, luminescence-based oxygen
      sensors, in particular, show great promise in their ability to be integrated with
      microfluidics and cell culture systems. These sensors can be highly sensitive and
      do not consume oxygen or generate toxic byproducts in their sensing process. This
      paper presents a review of previously proposed optical oxygen sensor types,
      materials and formats most applicable to microfluidic cell culture, and analyzes
      their suitability for this and other in vitro applications.

PMID- 22163409
TI  - Bioconjugation strategies for microtoroidal optical resonators.
AB  - The development of label-free biosensors with high sensitivity and specificity is
      of significant interest for medical diagnostics and environmental monitoring,
      where rapid and real-time detection of antigens, bacteria, viruses, etc., is
      necessary. Optical resonant devices, which have very high sensitivity resulting
      from their low optical loss, are uniquely suited to sensing applications.
      However, previous research efforts in this area have focused on the development
      of the sensor itself. While device sensitivity is an important feature of a
      sensor, specificity is an equally, if not more, important performance parameter.
      Therefore, it is crucial to develop a covalent surface functionalization process,
      which also maintains the device's sensing capabilities or optical qualities.
      Here, we demonstrate a facile method to impart specificity to optical
      microcavities, without adversely impacting their optical performance. In this
      approach, we selectively functionalize the surface of the silica microtoroids
      with biotin, using amine-terminated silane coupling agents as linkers. The
      surface chemistry of these devices is demonstrated using X-ray photoelectron
      spectroscopy, and fluorescent and optical microscopy. The quality factors of the
      surface functionalized devices are also characterized to determine the impact of
      the chemistry methods on the device sensitivity. The resulting devices show
      uniform surface coverage, with no microstructural damage. This work represents
      one of the first examples of non-physisorption-based bioconjugation of
      microtoroidal optical resonators.

PMID- 22163410
TI  - Design of a horizontal penetrometer for measuring on-the-go soil resistance.
AB  - Soil compaction is one of the main negative factors that limits plant growth and
      crop yield. Therefore, it is important to determine the soil resistance level and
      map it for the field to find solutions for the negative effects of the
      compaction. Nowadays, high powered communication technology and computers help us
      on this issue within the approach of precision agriculture applications. This
      study is focused on the design of a penetrometer, which can make instantaneous
      soil resistance measurements in the soil horizontally and data acquisition
      software based on the GPS (Global Positioning System). The penetrometer was
      designed using commercial 3D parametric solid modelling design software. The data
      acquisition software was developed in Microsoft Visual Basic.NET programming
      language. After the design of the system, manufacturing and assembly of the
      system was completed and then a field experiment was carried out. According to
      the data from GPS and penetration resistance values which are collected in
      Microsoft SQL Server database, a Kriging method by ArcGIS was used and soil
      resistance was mapped in the field for a soil depth of 40 cm. During operation,
      no faults, either in mechanical and software parts, were seen. As a result, soil
      resistance values of 0.2 MPa and 3 MPa were obtained as minimum and maximum
      values, respectively. In conclusion, the experimental results showed that the
      designed system works quite well in the field and the horizontal penetrometer is
      a practical tool for providing on-line soil resistance measurements. This study
      contributes to further research for the development of on-line soil resistance
      measurements and mapping within the precision agriculture applications.

PMID- 22163411
TI  - A reliable data delivery mechanism for grid power quality using neural networks
      in wireless sensor networks.
AB  - Power grids deal with the business of generation, transmission, and distribution
      of electric power. Current systems monitor basic electrical quantities such as
      voltage and current from major pole transformers using their temperature. We
      improve the current systems in order to gather and deliver the information of
      power qualities such as harmonics, voltage sags, and voltage swells. In the
      system, data delivery is not guaranteed for the case that a node is lost or the
      network is congested, because the system has in-line and multi-hop architecture.
      In this paper, we propose a reliable data delivery mechanism by modeling an
      optimal data delivery function by employing the neural network concept.

PMID- 22163412
TI  - A sulfur hexafluoride sensor using quantum cascade and CO2 laser-based
      photoacoustic spectroscopy.
AB  - The increase in greenhouse gas emissions is a serious environmental problem and
      has stimulated the scientific community to pay attention to the need for
      detection and monitoring of gases released into the atmosphere. In this regard,
      the development of sensitive and selective gas sensors has been the subject of
      several research programs. An important greenhouse gas is sulphur hexafluoride,
      an almost non-reactive gas widely employed in industrial processes worldwide.
      Indeed it is estimated that it has a radiative forcing of 0.52 W/m(2). This work
      compares two photoacoustic spectrometers, one coupled to a CO(2) laser and
      another one coupled to a Quantum Cascade (QC) laser, for the detection of SF(6).
      The laser photoacoustic spectrometers described in this work have been developed
      for gas detection at small concentrations. Detection limits of 20 ppbv for CO(2)
      laser and 50 ppbv for quantum cascade laser were obtained.

PMID- 22163413
TI  - Biomedical use of isothermal microcalorimeters.
AB  - Isothermal microcalorimetry is becoming widely used for monitoring biological
      activities in vitro. Microcalorimeters are now able to measure heat production
      rates of less than a microwatt. As a result, metabolism and growth of relatively
      small numbers of cultured bacteria, protozoans, human cells and even small
      animals can be monitored continuously and extremely accurately at any chosen
      temperature. Dynamic effects on these organisms of changes in the culture
      environment--or of additions to it--are easily assessed over periods from hours
      to days. In addition microcalorimetry is a non-destructive method that does not
      require much sample preparation. It is also completely passive and thus allows
      subsequent evaluations of any kind on the undisturbed sample. In this review, we
      present a basic description of current microcalorimetry instruments and an
      overview of their use for various biomedical applications. These include
      detecting infections, evaluating effects of pharmaceutical or antimicrobial
      agents on cells, monitoring growth of cells harvested for tissue eingineering,
      and assessing medical and surgical device material physico-chemical stability and
      cellular biocompatibility.

PMID- 22163414
TI  - Sensor data fusion for accurate cloud presence prediction using Dempster-Shafer
      evidence theory.
AB  - Sensor data fusion technology can be used to best extract useful information from
      multiple sensor observations. It has been widely applied in various applications
      such as target tracking, surveillance, robot navigation, signal and image
      processing. This paper introduces a novel data fusion approach in a multiple
      radiation sensor environment using Dempster-Shafer evidence theory. The
      methodology is used to predict cloud presence based on the inputs of radiation
      sensors. Different radiation data have been used for the cloud prediction. The
      potential application areas of the algorithm include renewable power for virtual
      power station where the prediction of cloud presence is the most challenging
      issue for its photovoltaic output. The algorithm is validated by comparing the
      predicted cloud presence with the corresponding sunshine occurrence data that
      were recorded as the benchmark. Our experiments have indicated that comparing to
      the approaches using individual sensors, the proposed data fusion approach can
      increase correct rate of cloud prediction by ten percent, and decrease unknown
      rate of cloud prediction by twenty three percent.

PMID- 22163415
TI  - E-beam patterned gold nanodot arrays on optical fiber tips for localized surface
      plasmon resonance biochemical sensing.
AB  - Electron beam lithography (EBL) was used to directly pattern periodic gold
      nanodot arrays on optical fiber tips. Localized surface plasmon resonance of the
      E-beam patterned gold nanodot arrays on optical fiber tips was utilized for
      biochemical sensing. The advantage of the optical fiber based localized surface
      plasmon resonance (LSPR) sensors is the convenience to work with and work in
      harsh environments. An optical fiber tip LSPR refractive index sensor of 196 nm
      per refractive index unit (RIU) sensitivity has been demonstrated. The affinity
      sensing property of the fiber tip sensor was demonstrated using
      biotin/streptavidin as the receptor/analyte. The detection limit for streptavidin
      was determined to be 6 pM.

PMID- 22163416
TI  - Fiber Bragg Grating sensor for fault detection in radial and network transmission
      lines.
AB  - In this paper, a fiber optic based sensor capable of fault detection in both
      radial and network overhead transmission power line systems is investigated.
      Bragg wavelength shift is used to measure the fault current and detect fault in
      power systems. Magnetic fields generated by currents in the overhead transmission
      lines cause a strain in magnetostrictive material which is then detected by Fiber
      Bragg Grating (FBG). The Fiber Bragg interrogator senses the reflected FBG
      signals, and the Bragg wavelength shift is calculated and the signals are
      processed. A broadband light source in the control room scans the shift in the
      reflected signal. Any surge in the magnetic field relates to an increased fault
      current at a certain location. Also, fault location can be precisely defined with
      an artificial neural network (ANN) algorithm. This algorithm can be easily
      coordinated with other protective devices. It is shown that the faults in the
      overhead transmission line cause a detectable wavelength shift on the reflected
      signal of FBG and can be used to detect and classify different kind of faults.
      The proposed method has been extensively tested by simulation and results confirm
      that the proposed scheme is able to detect different kinds of fault in both
      radial and network system.

PMID- 22163417
TI  - An integration of GPS with INS sensors for precise long-baseline kinematic
      positioning.
AB  - Integrating the precise GPS carrier phases and INS sensor technologies is a
      methodology that has been applied indispensably in those application fields
      requiring accurate and reliable position, velocity, and attitude information.
      However, conventional integration approaches with a single GPS reference station
      may not fulfil the demanding performance requirements, especially in the position
      component, when the baseline length between the reference station and mobile
      user's GPS receiver is greater than a few tens of kilometres. This is because
      their positioning performance is primarily dependent on the common mode of errors
      of GPS measurements. To address this constraint, a novel GPS/INS integration
      scheme using multiple GPS reference stations is proposed here that can improve
      its positioning accuracy by modelling the baseline-dependent errors. In this
      paper, the technical issues concerned with implementing the proposed scheme are
      described, including the GPS network correction modelling and integrated GPS/INS
      filtering. In addition, the results from the processing of the simulated
      measurements are presented to characterise the system performance. As a result,
      it has been established that the integration of GPS/INS with multiple reference
      stations would make it possible to ensure centimetre-level positioning accuracy,
      even if the baseline length reaches about 100 km.

PMID- 22163418
TI  - Development of an electrochemical biosensor for the detection of aflatoxin M1 in
      milk.
AB  - We have developed an electrochemical immunosensor for the detection of ultratrace
      amounts of aflatoxin M(1) (AFM(1)) in food products. The sensor was based on a
      competitive immunoassay using horseradish peroxidase (HRP) as a tag. Magnetic
      nanoparticles coated with antibody (anti-AFM(1)) were used to separate the bound
      and unbound fractions. The samples containing AFM(1) were incubated with a fixed
      amount of antibody and tracer [AFM(1) linked to HRP (conjugate)] until the system
      reached equilibrium. Competition occurs between the antigen (AFM(1)) and the
      conjugate for the antibody. Then, the mixture was deposited on the surface of
      screen-printed carbon electrodes, and the mediator [5-methylphenazinium methyl
      sulphate (MPMS)] was added. The enzymatic response was measured amperometrically.
      A standard range (0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, 0.3, 0.4 and 0.5 ppb)
      of AFM(1)-contaminated milk from the ELISA kit was used to obtain a standard
      curve for AFM(1). To test the detection sensitivity of our sensor, samples of
      commercial milk were supplemented at 0.01, 0.025, 0.05 or 0.1 ppb with AFM(1).
      Our immunosensor has a low detection limit (0.01 ppb), which is under the
      recommended level of AFM(1) [0.05 MUg L-1 (ppb)], and has good reproducibility.

PMID- 22163419
TI  - Determination of anthracene on Ag-Au alloy nanoparticles/overoxidized-polypyrrole
      composite modified glassy carbon electrodes.
AB  - A novel electrochemical sensor for the detection of anthracene was prepared by
      modifying a glassy carbon electrode (GCE) with over-oxidized polypyrrole (PPyox)
      and Ag-Au (1:3) bimetallic nanoparticles (Ag-AuNPs). The composite electrode
      (PPyox/Ag-AuNPs/GCE) was prepared by potentiodynamic polymerization of pyrrole on
      GCE followed by its overoxidation in 0.1 M NaOH. Ag-Au bimetallic nanoparticles
      were chemically prepared by the reduction of AgNO(3) and HAuCl(4) using
      C(6)H(5)O(7)Na(3) as the reducing agent as well as the capping agent and then
      immobilized on the surface of the PPyox/GCE. The nanoparticles were characterized
      by UV-visible spectroscopy technique which confirmed the homogeneous formation of
      the bimetallic alloy nanoparticles. Transmission electron microscopy showed that
      the synthesized bimetallic nanoparticles were in the range of 20-50 nm. The
      electrochemical behaviour of anthracene at the PPyox/Ag-AuNPs/GCE with Ag: Au
      atomic ratio 25:75 (1:3) exhibited a higher electrocatalytic effect compared to
      that observed when GCE was modified with each constituent of the composite (i.e.,
      PPyox, Ag-AuNPs) and bare GCE. A linear relationship between anodic current and
      anthracene concentration was attained over the range of 3.0 * 10(-6) to 3.56 *
      10(-4) M with a detection limit of 1.69 * 10(-7) M. The proposed method was
      simple, less time consuming and showed a high sensitivity.

PMID- 22163420
TI  - A schedule-based multi-channel MAC protocol for wireless sensor networks.
AB  - Due to the half-duplex property of the sensor radio and the broadcast nature of
      wireless medium, limited bandwidth remains a pressing issue for wireless sensor
      networks (WSNs). The design of multi-channel MAC protocols has attracted the
      interest of many researchers as a cost effective solution to meet the higher
      bandwidth demand for the limited bandwidth in WSN. In this paper, we present a
      scheduled-based multi-channel MAC protocol to improve network performance. In our
      protocol, each receiving node selects (schedules) some timeslot(s), in which it
      may receive data from the intending sender(s). The timeslot selection is done in
      a conflict free manner, where a node avoids the slots that are already selected
      by others in its interference range. To minimize the conflicts during timeslot
      selection, we propose a unique solution by splitting the neighboring nodes into
      different groups, where nodes of a group may select the slots allocated to that
      group only. We demonstrate the effectiveness of our approach thorough simulations
      in terms of performance parameters such as aggregate throughput, packet delivery
      ratio, end-to-end delay, and energy consumption.

PMID- 22163421
TI  - Study on a luminol-based electrochemiluminescent sensor for label-free DNA
      sensing.
AB  - Automatic, inexpensive, simple and sensitive methods for DNA sensing and
      quantification are highly desirable for biomedical research. The rapid
      development of both the fundamentals and applications of electrochemiluminescence
      (ECL) over the past years has demonstrated its potential for analytical and bio
      analytical chemistry. This paper reports the quenching effect of DNA on the ECL
      of luminol and the further development of a DNA sensing device. With the pre
      functionalization by a composite of carbon nano-tubes (CNTs) and Au nanoparticles
      (AuNPs), the sensor provides a novel and valuable label-free approach for DNA
      sensing. Here the ECL intensity was remarkably decreased when more than 1.0 * 10(
      12) molar of DNA were adsorbed on the sensor. Linearity of the DNA amount with
      the reciprocal of ECL intensity was observed. A saturated sensor caused a 92.8%
      quenching effect. The research also proposes the mechanism for the quenching
      effect which could be attributed to the interaction between luminol and DNA and
      the elimination of reactive oxygen species (ROSs) by DNA.

PMID- 22163422
TI  - A Distance-based Energy Aware Routing algorithm for wireless sensor networks.
AB  - Energy efficiency and balancing is one of the primary challenges for wireless
      sensor networks (WSNs) since the tiny sensor nodes cannot be easily recharged
      once they are deployed. Up to now, many energy efficient routing algorithms or
      protocols have been proposed with techniques like clustering, data aggregation
      and location tracking etc. However, many of them aim to minimize parameters like
      total energy consumption, latency etc., which cause hotspot nodes and partitioned
      network due to the overuse of certain nodes. In this paper, a Distance-based
      Energy Aware Routing (DEAR) algorithm is proposed to ensure energy efficiency and
      energy balancing based on theoretical analysis of different energy and traffic
      models. During the routing process, we consider individual distance as the
      primary parameter in order to adjust and equalize the energy consumption among
      involved sensors. The residual energy is also considered as a secondary factor.
      In this way, all the intermediate nodes will consume their energy at similar
      rate, which maximizes network lifetime. Simulation results show that the DEAR
      algorithm can reduce and balance the energy consumption for all sensor nodes so
      network lifetime is greatly prolonged compared to other routing algorithms.

PMID- 22163423
TI  - Image reconstruction of a charge coupled device based optical tomographic
      instrumentation system for particle sizing.
AB  - This research investigates the use of charge coupled device (abbreviated as CCD)
      linear image sensors in an optical tomographic instrumentation system used for
      sizing particles. The measurement system, consisting of four CCD linear image
      sensors are configured around an octagonal shaped flow pipe for a four
      projections system is explained. The four linear image sensors provide 2,048
      pixel imaging with a pixel size of 14 micron * 14 micron, hence constituting a
      high-resolution system. Image reconstruction for a four-projection optical
      tomography system is also discussed, where a simple optical model is used to
      relate attenuation due to variations in optical density, [R], within the
      measurement section. Expressed in matrix form this represents the forward problem
      in tomography [S] [R] = [M]. In practice, measurements [M] are used to estimate
      the optical density distribution by solving the inverse problem [R] = [S](-1)[M].
      Direct inversion of the sensitivity matrix, [S], is not possible and two
      approximations are considered and compared-the transpose and the pseudo inverse
      sensitivity matrices.

PMID- 22163424
TI  - A feedback-based secure path approach for wireless sensor network data
      collection.
AB  - The unattended nature of wireless sensor networks makes them very vulnerable to
      malicious attacks. Therefore, how to preserve secure data collection is an
      important issue to wireless sensor networks. In this paper, we propose a novel
      approach of secure data collection for wireless sensor networks. We explore
      secret sharing and multipath routing to achieve secure data collection in
      wireless sensor network with compromised nodes. We present a novel tracing
      feedback mechanism, which makes full use of the routing functionality of wireless
      sensor networks, to improve the quality of data collection. The major advantage
      of the approach is that the secure paths are constructed as a by-product of data
      collection. The process of secure routing causes little overhead to the sensor
      nodes in the network. Compared with existing works, the algorithms of the
      proposed approach are easy to implement and execute in resource-constrained
      wireless sensor networks. According to the result of a simulation experiment, the
      performance of the approach is better than the recent approaches with a similar
      purpose.

PMID- 22163425
TI  - Novel designs for application specific MEMS pressure sensors.
AB  - In the framework of developing innovative microfabricated pressure sensors, we
      present here three designs based on different readout principles, each one
      tailored for a specific application. A touch mode capacitive pressure sensor with
      high sensitivity (14 pF/bar), low temperature dependence and high capacitive
      output signal (more than 100 pF) is depicted. An optical pressure sensor
      intrinsically immune to electromagnetic interference, with large pressure range
      (0-350 bar) and a sensitivity of 1 pm/bar is presented. Finally, a resonating
      wireless pressure sensor power source free with a sensitivity of 650 KHz/mmHg is
      described. These sensors will be related with their applications in harsh
      environment, distributed systems and medical environment, respectively. For many
      aspects, commercially available sensors, which in vast majority are
      piezoresistive, are not suited for the applications proposed.

PMID- 22163426
TI  - An agenda-based routing protocol in delay tolerant mobile sensor networks.
AB  - Routing in delay tolerant mobile sensor networks (DTMSNs) is challenging due to
      the networks' intermittent connectivity. Most existing routing protocols for
      DTMSNs use simplistic random mobility models for algorithm design and performance
      evaluation. In the real world, however, due to the unique characteristics of
      human mobility, currently existing random mobility models may not work well in
      environments where mobile sensor units are carried (such as DTMSNs). Taking a
      person's social activities into consideration, in this paper, we seek to improve
      DTMSN routing in terms of social structure and propose an agenda based routing
      protocol (ARP). In ARP, humans are classified based on their agendas and data
      transmission is made according to sensor nodes' transmission rankings. The
      effectiveness of ARP is demonstrated through comprehensive simulation studies.

PMID- 22163427
TI  - Design and implementation of a digital angular rate sensor.
AB  - With the aim of detecting the attitude of a rotating carrier, the paper presents
      a novel, digital angular rate sensor. The sensor consists of micro-sensing
      elements (gyroscope and accelerometer), signal processing circuit and micro
      processor (DSP2812). The sensor has the feature of detecting three angular rates
      of a rotating carrier at the same time. The key techniques of the sensor,
      including sensing construction, sensing principles, and signal processing circuit
      design are presented. The test results show that the sensor can sense rolling,
      pitch and yaw angular rate at the same time and the measurement error of yaw (or
      pitch) angular rate and rolling rate of the rotating carrier is less than 0.5%.

PMID- 22163428
TI  - An adaptive fault-tolerant communication scheme for body sensor networks.
AB  - A high degree of reliability for critical data transmission is required in body
      sensor networks (BSNs). However, BSNs are usually vulnerable to channel
      impairments due to body fading effect and RF interference, which may potentially
      cause data transmission to be unreliable. In this paper, an adaptive and flexible
      fault-tolerant communication scheme for BSNs, namely AFTCS, is proposed. AFTCS
      adopts a channel bandwidth reservation strategy to provide reliable data
      transmission when channel impairments occur. In order to fulfill the reliability
      requirements of critical sensors, fault-tolerant priority and queue are employed
      to adaptively adjust the channel bandwidth allocation. Simulation results show
      that AFTCS can alleviate the effect of channel impairments, while yielding lower
      packet loss rate and latency for critical sensors at runtime.

PMID- 22163429
TI  - A comparison between two heterodyne light sources using different electro-optic
      modulators for optical temperature measurements at visible wavelengths.
AB  - In this paper we have successfully demonstrated a z-propagating Zn-indiffused
      lithium niobate electro-optic modulator used for optical heterodyne
      interferometry. Compared to a commercial buck-type electro-optic modulator, the
      proposed waveguide-type modulator has a lower driving voltage and smaller phase
      variation while measuring visible wavelengths of 532 nm and 632.8 nm. We also
      demonstrate an optical temperature measurement system using a homemade modulator.
      The results show that the measurement sensitivities are almost the same values of
      25 deg/ degrees C for both the homemade and the buck-type modulators for a
      sensing light with a wavelength of 632.8 nm. Because photorefractive impacts are
      essential in the buck-type modulator at a wavelength of 532 nm, it is difficult
      to obtain reliable phase measurements, whereas the stable phase operation of the
      homemade one allows the measurement sensitivity to be improved up to 30 deg/
      degrees C with the best measurement resolution at about 0.07  degrees C for 532
      nm.

PMID- 22163430
TI  - Compact electromagnetic bandgap structures for notch band in ultra-wideband
      applications.
AB  - This paper introduces a novel approach to create notch band filters in the front
      end of ultra-wideband (UWB) communication systems based on electromagnetic
      bandgap (EBG) structures. The concept presented here can be implemented in any
      structure that has a microstrip in its configuration. The EBG structure is first
      analyzed using a full wave electromagnetic solver and then optimized to work at
      WLAN band (5.15-5.825 GHz). Two UWB passband filters are used to demonstrate the
      applicability and effectiveness of the novel EBG notch band feature. Simulation
      results are provided for two cases studied.

PMID- 22163432
TI  - Remote sensing of ecology, biodiversity and conservation: a review from the
      perspective of remote sensing specialists.
AB  - Remote sensing, the science of obtaining information via noncontact recording,
      has swept the fields of ecology, biodiversity and conservation (EBC). Several
      quality review papers have contributed to this field. However, these papers often
      discuss the issues from the standpoint of an ecologist or a biodiversity
      specialist. This review focuses on the spaceborne remote sensing of EBC from the
      perspective of remote sensing specialists, i.e., it is organized in the context
      of state-of-the-art remote sensing technology, including instruments and
      techniques. Herein, the instruments to be discussed consist of high spatial
      resolution, hyperspectral, thermal infrared, small-satellite constellation, and
      LIDAR sensors; and the techniques refer to image classification, vegetation index
      (VI), inversion algorithm, data fusion, and the integration of remote sensing
      (RS) and geographic information system (GIS).

PMID- 22163431
TI  - Theory and applications of surface plasmon resonance, resonant mirror, resonant
      waveguide grating, and dual polarization interferometry biosensors.
AB  - Biosensors have been used extensively in the scientific community for several
      purposes, most notably to determine association and dissociation kinetics,
      protein-ligand, protein-protein, or nucleic acid hybridization interactions. A
      number of different types of biosensors are available in the field, each with
      real or perceived benefits over the others. This review discusses the basic
      theory and operational arrangements of four commercially available types of
      optical biosensors: surface plasmon resonance, resonant mirror, resonance
      waveguide grating, and dual polarization interferometry. The different
      applications these techniques offer are discussed from experiments and results
      reported in recently published literature. Additionally, recent advancements or
      modifications to the current techniques are also discussed.

PMID- 22163433
TI  - An analytical model of joule heating in piezoresistive microcantilevers.
AB  - The present study investigates Joule heating in piezoresistive microcantilever
      sensors. Joule heating and thermal deflections are a major source of noise in
      such sensors. This work uses analytical and numerical techniques to characterise
      the Joule heating in 4-layer piezoresistive microcantilevers made of silicon and
      silicon dioxide substrates but with the same U-shaped silicon piezoresistor. A
      theoretical model for predicting the temperature generated due to Joule heating
      is developed. The commercial finite element software ANSYS Multiphysics was used
      to study the effect of electrical potential on temperature and deflection
      produced in the cantilevers. The effect of piezoresistor width on Joule heating
      is also studied. Results show that Joule heating strongly depends on the applied
      potential and width of piezoresistor and that a silicon substrate cantilever has
      better thermal characteristics than a silicon dioxide cantilever.

PMID- 22163434
TI  - Measuring relative-story displacement and local inclination angle using multiple
      position-sensitive detectors.
AB  - We propose a novel sensor system for monitoring the structural health of a
      building. The system optically measures the relative-story displacement during
      earthquakes for detecting any deformations of building elements. The sensor unit
      is composed of three position sensitive detectors (PSDs) and lenses capable of
      measuring the relative-story displacement precisely, even if the PSD unit was
      inclined in response to the seismic vibration. For verification, laboratory tests
      were carried out using an Xtheta-stage and a shaking table. The static experiment
      verified that the sensor could measure the local inclination angle as well as the
      lateral displacement. The dynamic experiment revealed that the accuracy of the
      sensor was 150 MUm in the relative-displacement measurement and 100 MUrad in the
      inclination angle measurement. These results indicate that the proposed sensor
      system has sufficient accuracy for the measurement of relative-story displacement
      in response to the seismic vibration.

PMID- 22163435
TI  - Hydrostatic pressure sensing with high birefringence photonic crystal fibers.
AB  - The effect of hydrostatic pressure on the waveguiding properties of high
      birefringence photonic crystal fibers (HiBi PCF) is evaluated both numerically
      and experimentally. A fiber design presenting form birefringence induced by two
      enlarged holes in the innermost ring defining the fiber core is investigated.
      Numerical results show that modal sensitivity to the applied pressure depends on
      the diameters of the holes, and can be tailored by independently varying the
      sizes of the large or small holes. Numerical and experimental results are
      compared showing excellent agreement. A hydrostatic pressure sensor is proposed
      and demonstrated using an in-fiber modal interferometer where the two
      orthogonally polarized modes of a HiBi PCF generate fringes over the optical
      spectrum of a broad band source. From the analysis of experimental results, it is
      concluded that, in principle, an operating limit of 92 MPa in pressure could be
      achieved with 0.0003% of full scale resolution.

PMID- 22163436
TI  - A design of wireless sensor networks for a power quality monitoring system.
AB  - Power grids deal with the business of generation, transmission, and distribution
      of electric power. Recently, interest in power quality in electrical distribution
      systems has increased rapidly. In Korea, the communication network to deliver
      voltage, current, and temperature measurements gathered from pole transformers to
      remote monitoring centers employs cellular mobile technology. Due to high cost of
      the cellular mobile technology, power quality monitoring measurements are limited
      and data gathering intervals are large. This causes difficulties in providing the
      power quality monitoring service. To alleviate the problems, in this paper we
      present a communication infrastructure to provide low cost, reliable data
      delivery. The communication infrastructure consists of wired connections between
      substations and monitoring centers, and wireless connections between pole
      transformers and substations. For the wireless connection, we employ a wireless
      sensor network and design its corresponding data forwarding protocol to improve
      the quality of data delivery. For the design, we adopt a tree-based data
      forwarding protocol in order to customize the distribution pattern of the power
      quality information. We verify the performance of the proposed data forwarding
      protocol quantitatively using the NS-2 network simulator.

PMID- 22163437
TI  - Detection of greenhouse gas precursors from diesel engines using electrochemical
      and photoacoustic sensors.
AB  - Atmospheric pollution is one of the worst threats to modern society. The
      consequences derived from different forms of atmospheric pollution vary from the
      local to the global scale, with deep impacts on climate, environment and human
      health. Several gaseous pollutants, even when present in trace concentrations,
      play a fundamental role in important processes that occur in atmosphere.
      Phenomena such as global warming, photochemical smog formation, acid rain and the
      depletion of the stratospheric ozone layer are strongly related to the increased
      concentration of certain gaseous species in the atmosphere. The transport sector
      significantly produces atmospheric pollution, mainly when diesel oil is used as
      fuel. Therefore, new methodologies based on selective and sensitive gas detection
      schemes must be developed in order to detect and monitor pollutant gases from
      this source. In this work, CO(2) Laser Photoacoustic Spectroscopy was used to
      evaluate ethylene emissions and electrochemical analyzers were used to evaluate
      the emissions of CO, NO(x) and SO(2) from the exhaust of diesel powered vehicles
      (rural diesel with 5% of biodiesel, in this paper called only diesel) at
      different engine rotation speeds. Concentrations in the range 6 to 45 ppmV for
      ethylene, 109 to 1,231 ppmV for carbon monoxide, 75 to 868 ppmV for nitrogen
      oxides and 3 to 354 ppmV for sulfur dioxide were obtained. The results indicate
      that the detection techniques used were sufficiently selective and sensitive to
      detect the gaseous species mentioned above in the ppmV range.

PMID- 22163438
TI  - Adaptive AOA-aided TOA self-positioning for mobile wireless sensor networks.
AB  - Location-awareness is crucial and becoming increasingly important to many
      applications in wireless sensor networks. This paper presents a network-based
      positioning system and outlines recent work in which we have developed an
      efficient principled approach to localize a mobile sensor using time of arrival
      (TOA) and angle of arrival (AOA) information employing multiple seeds in the line
      of-sight scenario. By receiving the periodic broadcasts from the seeds, the
      mobile target sensors can obtain adequate observations and localize themselves
      automatically. The proposed positioning scheme performs location estimation in
      three phases: (I) AOA-aided TOA measurement, (II) Geometrical positioning with
      particle filter, and (III) Adaptive fuzzy control. Based on the distance
      measurements and the initial position estimate, adaptive fuzzy control scheme is
      applied to solve the localization adjustment problem. The simulations show that
      the proposed approach provides adaptive flexibility and robust improvement in
      position estimation.

PMID- 22163439
TI  - MQ-MAC: a multi-constrained QoS-aware duty cycle MAC for heterogeneous traffic in
      wireless sensor networks.
AB  - Energy conservation is one of the striking research issues now-a-days for power
      constrained wireless sensor networks (WSNs) and hence, several duty-cycle based
      MAC protocols have been devised for WSNs in the last few years. However,
      assimilation of diverse applications with different QoS requirements (i.e., delay
      and reliability) within the same network also necessitates in devising a generic
      duty-cycle based MAC protocol that can achieve both the delay and reliability
      guarantee, termed as multi-constrained QoS, while preserving the energy
      efficiency. To address this, in this paper, we propose a Multi-constrained QoS
      aware duty-cycle MAC for heterogeneous traffic in WSNs (MQ-MAC). MQ-MAC
      classifies the traffic based on their multi-constrained QoS demands. Through
      extensive simulation using ns-2 we evaluate the performance of MQ-MAC. MQ-MAC
      provides the desired delay and reliability guarantee according to the nature of
      the traffic classes as well as achieves energy efficiency.

PMID- 22163440
TI  - A dipping duration study for optimization of anodized-aluminum pressure-sensitive
      paint.
AB  - Anodized-aluminum pressure-sensitive paint (AA-PSP) uses the dipping deposition
      method to apply a luminophore on a porous anodized-aluminum surface. We study the
      dipping duration, one of the parameters of the dipping deposition related to the
      characterization of AA-PSP. The dipping duration was varied from 1 to 100,000 s.
      The properties characterized are the pressure sensitivity, temperature
      dependency, and signal level. The maximum pressure sensitivity of 65% is obtained
      at the dipping duration of 100 s, the minimum temperature dependency is obtained
      at the duration of 1 s, and the maximum signal level is obtained at the duration
      of 1,000 s, respectively. Among the characteristics, the dipping duration most
      influences the signal level. The change in the signal level is a factor of 8.4.
      By introducing a weight coefficient, an optimum dipping duration can be
      determined. Among all the dipping parameters, such as the dipping duration,
      dipping solvent, and luminophore concentration, the pressure sensitivity and
      signal level are most influenced by the dipping solvent.

PMID- 22163441
TI  - Optical sensing with simultaneous electrochemical control in metal nanowire
      arrays.
AB  - This work explores the alternative use of noble metal nanowire systems in large
      scale array configurations to exploit both the nanowires' conductive nature and
      localized surface plasmon resonance (LSPR). The first known nanowire-based system
      has been constructed, with which optical signals are influenced by the
      simultaneous application of electrochemical potentials. Optical characterization
      of nanowire arrays was performed by measuring the bulk refractive index
      sensitivity and the limit of detection. The formation of an electrical double
      layer was controlled in NaCl solutions to study the effect of local refractive
      index changes on the spectral response. Resonance peak shifts of over 4 nm, a
      bulk refractive index sensitivity up to 115 nm/RIU and a limit of detection as
      low as 4.5 * 10(-4) RIU were obtained for gold nanowire arrays. Simulations with
      the Multiple Multipole Program (MMP) confirm such bulk refractive index
      sensitivities. Initial experiments demonstrated successful optical biosensing
      using a novel form of particle-based nanowire arrays. In addition, the formation
      of an ionic layer (Stern-layer) upon applying an electrochemical potential was
      also monitored by the shift of the plasmon resonance.

PMID- 22163442
TI  - Metaphase FISH on a chip: miniaturized microfluidic device for fluorescence in
      situ hybridization.
AB  - Fluorescence in situ Hybridization (FISH) is a major cytogenetic technique for
      clinical genetic diagnosis of both inherited and acquired chromosomal
      abnormalities. Although FISH techniques have evolved and are often used together
      with other cytogenetic methods like CGH, PRINS and PNA-FISH, the process
      continues to be a manual, labour intensive, expensive and time consuming
      technique, often taking over 3 5 days, even in dedicated labs. We have developed
      a novel microFISH device to perform metaphase FISH on a chip which overcomes many
      shortcomings of the current laboratory protocols. This work also introduces a
      novel splashing device for preparing metaphase spreads on a microscope glass
      slide, followed by a rapid adhesive tape-based bonding protocol leading to rapid
      fabrication of the microFISH device. The microFISH device allows for an optimized
      metaphase FISH protocol on a chip with over a 20-fold reduction in the reagent
      volume. This is the first demonstration of metaphase FISH on a microfluidic
      device and offers a possibility of automation and significant cost reduction of
      many routine diagnostic tests of genetic anomalies.

PMID- 22163443
TI  - A tunable strain sensor using nanogranular metals.
AB  - This paper introduces a new methodology for the fabrication of strain-sensor
      elements for MEMS and NEMS applications based on the tunneling effect in nano
      granular metals. The strain-sensor elements are prepared by the maskless
      lithography technique of focused electron-beam-induced deposition (FEBID)
      employing the precursor trimethylmethylcyclopentadienyl platinum [MeCpPt(Me)(3)].
      We use a cantilever-based deflection technique to determine the sensitivity
      (gauge factor) of the sensor element. We find that its sensitivity depends on the
      electrical conductivity and can be continuously tuned, either by the thickness of
      the deposit or by electron-beam irradiation leading to a distinct maximum in the
      sensitivity. This maximum finds a theoretical rationale in recent advances in the
      understanding of electronic charge transport in nano-granular metals.

PMID- 22163444
TI  - A study on software-based sensing technology for multiple object control in AR
      video.
AB  - Researches on Augmented Reality (AR) have recently received attention. With
      these, the Machine-to-Machine (M2M) market has started to be active and there are
      numerous efforts to apply this to real life in all sectors of society. To date,
      the M2M market has applied the existing marker-based AR technology in
      entertainment, business and other industries. With the existing marker-based AR
      technology, a designated object can only be loaded on the screen from one marker
      and a marker has to be added to load on the screen the same object again. This
      situation creates a problem where the relevant marker'should be extracted and
      printed in screen so that loading of the multiple objects is enabled. However,
      since the distance between markers will not be measured in the process of
      detecting and copying markers, the markers can be overlapped and thus the objects
      would not be augmented. To solve this problem, a circle having the longest radius
      needs to be created from a focal point of a marker to be copied, so that no
      object is copied within the confines of the circle. In this paper, software-based
      sensing technology for multiple object detection and loading using PPHT has been
      developed and overlapping marker control according to multiple object control has
      been studied using the Bresenham and Mean Shift algorithms.

PMID- 22163445
TI  - Electrochemical aptasensor for endocrine disrupting 17beta-estradiol based on a
      poly(3,4-ethylenedioxylthiopene)-gold nanocomposite platform.
AB  - A simple and highly sensitive electrochemical DNA aptasensor with high affinity
      for endocrine disrupting 17beta-estradiol, was developed. Poly(3,4
      ethylenedioxylthiophene) (PEDOT) doped with gold nanoparticles (AuNPs) was
      electrochemically synthesized and employed for the immobilization of biotinylated
      aptamer towards the detection of the target. The diffusion coefficient of the
      nanocomposite was 6.50 * 10(-7) cm(2) s(-1), which showed that the nanocomposite
      was highly conducting. Electrochemical impedance investigation also revealed the
      catalytic properties of the nanocomposite with an exchange current value of 2.16
      * 10(-4) A, compared to 2.14 * 10(-5) A obtained for the bare electrode.
      Streptavidin was covalently attached to the platform using carbodiimide chemistry
      and the aptamer immobilized via streptavidin-biotin interaction. The
      electrochemical signal generated from the aptamer-target molecule interaction was
      monitored electrochemically using cyclic voltammetry and square wave voltammetry
      in the presence of [Fe(CN)(6)](-3/-4) as a redox probe. The signal observed shows
      a current decrease due to interference of the bound 17beta-estradiol. The current
      drop was proportional to the concentration of 17beta-estradiol. The PEDOT/AuNP
      platform exhibited high electroactivity, with increased peak current. The
      platform was found suitable for the immobilization of the DNAaptamer. The
      aptasensor was able to distinguish 17beta-estradiol from structurally similar
      endocrine disrupting chemicals denoting its specificity to 17beta-estradiol. The
      detectable concentration range of the 17beta-estradiol was 0.1 nM-100 nM, with a
      detection limit of 0.02 nM.

PMID- 22163446
TI  - A wireless sensor network based personnel positioning scheme in coal mines with
      blind areas.
AB  - This paper proposes a novel personnel positioning scheme for a tunnel network
      with blind areas, which compared with most existing schemes offers both low-cost
      and high-precision. Based on the data models of tunnel networks, measurement
      networks and mobile miners, the global positioning method is divided into four
      steps: (1) calculate the real time personnel location in local areas using a
      location engine, and send it to the upper computer through the gateway; (2)
      correct any localization errors resulting from the underground tunnel
      environmental interference; (3) determine the global three-dimensional position
      by coordinate transformation; (4) estimate the personnel locations in the blind
      areas. A prototype system constructed to verify the positioning performance shows
      that the proposed positioning system has good reliability, scalability, and
      positioning performance. In particular, the static localization error of the
      positioning system is less than 2.4 m in the underground tunnel environment and
      the moving estimation error is below 4.5 m in the corridor environment. The
      system was operated continuously over three months without any failures.

PMID- 22163447
TI  - MAC-bridging for multi-PHYs communication in BAN.
AB  - Body Area Network (BAN) is a collection of low-power, miniaturised, and
      intelligent sensor nodes that are used for unobtrusive and ambulatory health
      monitoring of a patient without any additional constraints. These nodes operate
      on different frequency bands or Multiple Physical Layers (Multi-PHYs).
      Additionally, some BAN applications demand a logical connection between different
      nodes working on different Multi-PHYs. In this paper, the idea of controlling
      Multi-PHYs using one MAC protocol is introduced. Unlike existing procedures where
      different nodes working on different channels are connected at the link layer
      bridging/switching, the proposed procedure called bridging logically connects
      them at the MAC layer. In other words, the bridge is used to relay or filter
      packets between different PHYs in the same BAN. Numerical approximations are
      presented to analyze the stochastic behaviour of the bridges, all of them having
      Multi-PHYs interfaces. The MICS and the ISM bands are regarded as PHY1 and PHY2,
      respectively. The performance results are presented for PHY2 (given that data is
      already received from PHY1) in terms of probability of successful transmission,
      number of failed requests, power consumption, and delay. Simulations are
      conducted to validate the analytical results. It can be seen that the deployment
      of multiple bridges along with the corresponding nodes allows Multi-PHYs
      communication with high transmission probability, low power consumption, and
      tolerable delay.

PMID- 22163448
TI  - QMRPF-UKF master-slave filtering for the attitude determination of micro-nano
      satellites using gyro and magnetometer.
AB  - In this paper, the problem of estimating the attitude of a micro-nano satellite,
      obtaining geomagnetic field measurements via a three-axis magnetometer and
      obtaining angle rate via gyro, is considered. For this application, a QMRPF-UKF
      master-slave filtering method is proposed, which uses the QMRPF and UKF
      algorithms to estimate the rotation quaternion and the gyro bias parameters,
      respectively. The computational complexicity related to the particle filtering
      technique is eliminated by introducing a multiresolution approach that permits a
      significant reduction in the number of particles. This renders QMRPF-UKF master
      slave filter computationally efficient and enables its implementation with a
      remarkably small number of particles. Simulation results by using QMRPF-UKF are
      given, which demonstrate the validity of the QMRPF-UKF nonlinear filter.

PMID- 22163449
TI  - Application of sensing techniques to cellular force measurement.
AB  - Cell traction forces (CTFs) are the forces produced by cells and exerted on
      extracellular matrix or an underlying substrate. CTFs function to maintain cell
      shape, enable cell migration, and generate and detect mechanical signals. As
      such, they play a vital role in many fundamental biological processes, including
      angiogenesis, inflammation, and wound healing. Therefore, a close examination of
      CTFs can enable better understanding of the cellular and molecular mechanisms of
      such processes. To this end, various force-sensing techniques for CTF measurement
      have been developed over the years. This article will provide a concise review of
      these sensing techniques and comment on the needs for improved force-sensing
      technologies for cell mechanics and biology research.

PMID- 22163450
TI  - A potentiometric formaldehyde biosensor based on immobilization of alcohol
      oxidase on acryloxysuccinimide-modified acrylic microspheres.
AB  - A new alcohol oxidase (AOX) enzyme-based formaldehyde biosensor based on acrylic
      microspheres has been developed. Hydrophobic poly(n-butyl acrylate-N-acryloxy
      succinimide) [poly(nBA-NAS)] microspheres, an enzyme immobilization matrix, was
      synthesized using photopolymerization in an emulsion form. AOX-poly(nBA-NAS)
      microspheres were deposited on a pH transducer made from a layer of photocured
      and self-plasticized polyacrylate membrane with an entrapped pH ionophore coated
      on a Ag/AgCl screen printed electrode (SPE). Oxidation of formaldehyde by the
      immobilized AOX resulted in the production of protons, which can be determined
      via the pH transducer. Effects of buffer concentrations, pH and different amount
      of immobilization matrix towards the biosensor's analytical performance were
      investigated. The formaldehyde biosensor exhibited a dynamic linear response
      range to formaldehyde from 0.3-316.2 mM and a sensitivity of 59.41 +/- 0.66
      mV/decade (R(2) = 0.9776, n = 3). The lower detection limit of the biosensor was
      0.3 mM, while reproducibility and repeatability were 3.16% RSD (relative standard
      deviation) and 1.11% RSD, respectively (n = 3). The use of acrylic microspheres
      in the potentiometric formaldehyde biosensor improved the biosensor's performance
      in terms of response time, linear response range and long term stability when
      compared with thick film immobilization methods.

PMID- 22163451
TI  - Sensitivities of a standard test method for the determination of the pHe of
      bioethanol and suggestions for improvement.
AB  - An assessment of the sensitivities of the critical parameters in the ASTM D6423
      documentary standard method for the measurement of pHe in (bio)ethanol has been
      undertaken. Repeatability of measurements made using the same glass electrode and
      reproducibility between different glass electrodes have been identified as the
      main contributors to the uncertainty of the values produced. Strategies to reduce
      the uncertainty of the measurement have been identified and tested. Both
      increasing the time after which the pHe measurement is made following immersion
      in the sample, and rinsing the glass electrode with ethanol prior to immersion in
      the sample, have been shown to be effective in reducing the uncertainty of the
      numerical value produced. However, it is acknowledged that the values produced
      using these modified approaches may not be directly compared with those obtained
      using the documentary ASTM method since pHe is defined operationally by the
      process used to measure it.

PMID- 22163452
TI  - Goniometer crosstalk compensation for knee joint applications.
AB  - Electrogoniometers are prone to crosstalk errors related to endblocks rotation
      (general crosstalk) and to the characteristics of each sensor (individual
      crosstalk). The aim of this study was to assess the crosstalk errors due to
      endblock misalignments and to propose a procedure to compensate for these errors
      in knee applications. A precision jig was used to simulate pure +/- 100 degrees 
      flexion/extension movements. A goniometer was mounted with various degrees of
      valgus/varus (+/- 20 degrees ) and rotation (+/- 30 degrees ) misalignments. For
      valgus/varus misalignments, although offset compensation eliminated the error in
      the valgus/varus recordings for 0 degrees  of flexion/extension and reduced it to
      a few degrees for small (+/- 30 degrees ) flexion/extension angles (root mean
      square error = 1.1 degrees ), the individual crosstalk caused pronounced errors
      for large (+/- 100 degrees ) angles (18.8 degrees ). Subsequent compensation for
      this crosstalk reduced these errors to 0.8 degrees  and 4.5 degrees ,
      respectively. For rotational misalignment, compensation for the general crosstalk
      by means of coordinate system rotation, in combination with compensation for the
      individual crosstalk, reduced the errors for small (+/- 30 degrees ) and large
      (+/- 100 degrees ) flexion/extension angles from 3.6 degrees  to 0.5 degrees  and
      from 15.5 degrees  to 2.4 degrees , respectively. Crosstalk errors were
      efficiently compensated by the procedures applied, which might be useful in
      preprocessing of knee functional data, thereby substantially improving goniometer
      accuracy.

PMID- 22163453
TI  - A QoS scheme for a congestion core network based on dissimilar QoS structures in
      smart-phone environments.
AB  - This study suggests an approach to effective transmission of multimedia content
      in a rapidly changing Internet environment including smart-phones. Guaranteeing
      QoS in networks is currently an important research topic. When transmitting
      Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network
      A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand,
      network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this
      case, the AF1 packets that received the best quality of service in network A will
      receive the lowest in network B, which may result in dropping of packets in
      network B and vice versa. This study suggests a way to guarantee QoS between
      hosts by minimizing the loss of AF packet class when one network transmits AF
      class packets to another network with differing principles. It is expected that
      QoS guarantees and their experimental value may be utilized as principles which
      can be applied to various mobile-web environments based on smart-phones.

PMID- 22163454
TI  - Effects of the intermittent pneumatic circulator on blood pressure during
      hemodialysis.
AB  - Hypotension is frequently reported during hemodialysis. This study aimed to
      examine the effect of the intermittent pneumatic circulator on blood pressure
      during hemodialysis. Sixteen subjects with chronic hemodialysis were recruited.
      Each subject randomly received two test conditions on separate days, hemodialysis
      with and without the circulator. The circulator was applied to the subject on
      lower extremities during 0.5-1 hr, 1.5-2 hr, 2.5-3 hr, and 3.5-4 hr of
      hemodialysis. Systolic and diastolic blood pressures (SBP and DBP) and heart rate
      (HR) were analyzed at pre-dialysis, 1 hr, 2 hr, and 3 hr of hemodialysis. Stroke
      volume (SV) and cardiac output (CO) were evaluated between 2.5 and 3.0 hr of
      hemodialysis. Blood chemicals (sodium, calcium, potassium, and phosphorous) and
      Kt/V before and after each hemodialysis session were analyzed. The number of
      episodes of hypotension was also recorded. The circulator intervention
      significantly improved SBP and DBP across all time points (P = 0.002 for SBP; P =
      0.002 for DBP). The frequency of hypotension was significantly decreased (P =
      0.028). SV and CO were significantly improved with the circulator intervention (P
      = 0.017 for SV; P = 0.026 for CO) and no statistical significances were found on
      blood chemicals or Kt/V analyses. The results suggested that the circulator
      intervention helps stabilize blood pressure and appears to be a practical
      treatment. Future studies are suggested to develop new circulator innovations
      with sensor feedback systems to enhance safety and maximize treatment efficiency.

PMID- 22163455
TI  - A novel acoustic sensor approach to classify seeds based on sound absorption
      spectra.
AB  - A non-destructive and novel in situ acoustic sensor approach based on the sound
      absorption spectra was developed for identifying and classifying different seed
      types. The absorption coefficient spectra were determined by using the impedance
      tube measurement method. Subsequently, a multivariate statistical analysis, i.e.,
      principal component analysis (PCA), was performed as a way to generate a
      classification of the seeds based on the soft independent modelling of class
      analogy (SIMCA) method. The results show that the sound absorption coefficient
      spectra of different seed types present characteristic patterns which are highly
      dependent on seed size and shape. In general, seed particle size and sphericity
      were inversely related with the absorption coefficient. PCA presented reliable
      grouping capabilities within the diverse seed types, since the 95% of the total
      spectral variance was described by the first two principal components.
      Furthermore, the SIMCA classification model based on the absorption spectra
      achieved optimal results as 100% of the evaluation samples were correctly
      classified. This study contains the initial structuring of an innovative method
      that will present new possibilities in agriculture and industry for classifying
      and determining physical properties of seeds and other materials.

PMID- 22163456
TI  - Non-destructive optical monitoring of grape maturation by proximal sensing.
AB  - A new, commercial, fluorescence-based optical sensor for plant constituent
      assessment was recently introduced. This sensor, called the Multiplex((r)) (FORCE
      A, Orsay, France), was used to monitor grape maturation by specifically
      monitoring anthocyanin accumulation. We derived the empirical anthocyanin content
      calibration curves for Champagne red grape cultivars, and we also propose a
      general model for the influence of the proportion of red berries, skin
      anthocyanin content and berry size on Multiplex((r)) indices. The Multiplex((r))
      was used on both berry samples in the laboratory and on intact clusters in the
      vineyard. We found that the inverted and log-transformed far-red fluorescence
      signal called the FERARI index, although sensitive to sample size and distance,
      is potentially the most widely applicable. The more robust indices, based on
      chlorophyll fluorescence excitation ratios, showed three ranges of dependence on
      anthocyanin content. We found that up to 0.16 mg cm(-2), equivalent to
      approximately 0.6 mg g(-1), all indices increase with accumulation of skin
      anthocyanin content. Excitation ratio-based indices decrease with anthocyanin
      accumulation beyond 0.27 mg cm(-2). We showed that the Multiplex((r)) can be
      advantageously used in vineyards on intact clusters for the non-destructive
      assessment of anthocyanin content of vine blocks and can now be tested on other
      fruits and vegetables based on the same model.

PMID- 22163457
TI  - A method for evaluating dynamical friction in linear ball bearings.
AB  - A method is proposed for evaluating the dynamical friction of linear bearings,
      whose motion is not perfectly linear due to some play in its internal mechanism.
      In this method, the moving part of a linear bearing is made to move freely, and
      the force acting on the moving part is measured as the inertial force given by
      the product of its mass and the acceleration of its centre of gravity. To
      evaluate the acceleration of its centre of gravity, the acceleration of two
      different points on it is measured using a dual-axis optical interferometer.

PMID- 22163458
TI  - Performance evaluation of an infrared thermocouple.
AB  - The measurement of the leaf temperature of forests or agricultural plants is an
      important technique for the monitoring of the physiological state of crops. The
      infrared thermometer is a convenient device due to its fast response and
      nondestructive measurement technique. Nowadays, a novel infrared thermocouple,
      developed with the same measurement principle of the infrared thermometer but
      using a different detector, has been commercialized for non-contact temperature
      measurement. The performances of two-kinds of infrared thermocouples were
      evaluated in this study. The standard temperature was maintained by a temperature
      calibrator and a special black cavity device. The results indicated that both
      types of infrared thermocouples had good precision. The error distribution ranged
      from -1.8  degrees C to 18  degrees C as the reading values served as the true
      values. Within the range from 13  degrees C to 37  degrees C, the adequate
      calibration equations were the high-order polynomial equations. Within the
      narrower range from 20  degrees C to 35  degrees C, the adequate equation was a
      linear equation for one sensor and a two-order polynomial equation for the other
      sensor. The accuracy of the two kinds of infrared thermocouple was improved by
      nearly 0.4  degrees C with the calibration equations. These devices could serve
      as mobile monitoring tools for in situ and real time routine estimation of leaf
      temperatures.

PMID- 22163459
TI  - Polypyrrole porous micro humidity sensor integrated with a ring oscillator
      circuit on chip.
AB  - This study presents the design and fabrication of a capacitive micro humidity
      sensor integrated with a five-stage ring oscillator circuit on chip using the
      complimentary metal oxide semiconductor (CMOS) process. The area of the humidity
      sensor chip is about 1 mm(2). The humidity sensor consists of a sensing capacitor
      and a sensing film. The sensing capacitor is constructed from spiral interdigital
      electrodes that can enhance the sensitivity of the sensor. The sensing film of
      the sensor is polypyrrole, which is prepared by the chemical polymerization
      method, and the film has a porous structure. The sensor needs a post-CMOS process
      to coat the sensing film. The post-CMOS process uses a wet etching to etch the
      sacrificial layers, and then the polypyrrole is coated on the sensing capacitor.
      The sensor generates a change in capacitance when the sensing film absorbs or
      desorbs vapor. The ring oscillator circuit converts the capacitance variation of
      the sensor into the oscillation frequency output. Experimental results show that
      the sensitivity of the humidity sensor is about 99 kHz/%RH at 25  degrees C.

PMID- 22163460
TI  - Feasibility of fiber Bragg grating and long-period fiber grating sensors under
      different environmental conditions.
AB  - This paper presents the feasibility of utilizing fiber Bragg grating (FBG) and
      long-period fiber grating (LPFG) sensors for nondestructive evaluation (NDE) of
      infrastructures using Portland cement concretes and asphalt mixtures for
      temperature, strain, and liquid-level monitoring. The use of hybrid FBG and LPFG
      sensors is aimed at utilizing the advantages of two kinds of fiber grating to
      implement NDE for monitoring strains or displacements, temperatures, and water
      levels of infrastructures such as bridges, pavements, or reservoirs for under
      different environmental conditions. Temperature fluctuation and stability tests
      were examined using FBG and LPFG sensors bonded on the surface of asphalt and
      concrete specimens. Random walk coefficient (RWC) and bias stability (BS) were
      used for the first time to indicate the stability performance of fiber grating
      sensors. The random walk coefficients of temperature variations between FBG (or
      LPFG) sensor and a thermocouple were found in the range of -0.7499  degrees C/
      [square root]h to -1.3548  degrees C/ [square root]h. In addition, the bias
      stability for temperature variations, during the fluctuation and stability tests
      with FBG (or LPFG) sensors were within the range of 0.01  degrees C/h with a 15
      18 h time cluster to 0.09  degrees C/h with a 3-4 h time cluster. This shows that
      the performance of FBG or LPFG sensors is comparable with that of conventional
      high-resolution thermocouple sensors under rugged conditions. The strain
      measurement for infrastructure materials was conducted using a packaged FBG
      sensor bonded on the surface of an asphalt specimen under indirect tensile
      loading conditions. A finite element modeling (FEM) was applied to compare
      experimental results of indirect tensile FBG strain measurements. For a
      comparative analysis between experiment and simulation, the FEM numerical results
      agreed with those from FBG strain measurements. The results of the liquid-level
      sensing tests show the LPFG-based sensor could discriminate five stationary
      liquid-levels and exhibits at least 1,050-mm liquid-level measurement capacity.
      Thus, the hybrid FBG and LPFG sensors reported here could benefit the NDE
      development and applications for infrastructure health monitoring such as strain,
      temperature and liquid-level measurements.

PMID- 22163461
TI  - Error analysis of terrestrial laser scanning data by means of spherical
      statistics and 3D graphs.
AB  - This paper presents a complete analysis of the positional errors of terrestrial
      laser scanning (TLS) data based on spherical statistics and 3D graphs. Spherical
      statistics are preferred because of the 3D vectorial nature of the spatial error.
      Error vectors have three metric elements (one module and two angles) that were
      analyzed by spherical statistics. A study case has been presented and discussed
      in detail. Errors were calculating using 53 check points (CP) and CP coordinates
      were measured by a digitizer with submillimetre accuracy. The positional accuracy
      was analyzed by both the conventional method (modular errors analysis) and the
      proposed method (angular errors analysis) by 3D graphics and numerical spherical
      statistics. Two packages in R programming language were performed to obtain
      graphics automatically. The results indicated that the proposed method is
      advantageous as it offers a more complete analysis of the positional accuracy,
      such as angular error component, uniformity of the vector distribution, error
      isotropy, and error, in addition the modular error component by linear
      statistics.

PMID- 22163462
TI  - Sensor based framework for secure multimedia communication in VANET.
AB  - Secure multimedia communication enhances the safety of passengers by providing
      visual pictures of accidents and danger situations. In this paper we proposed a
      framework for secure multimedia communication in Vehicular Ad-Hoc Networks
      (VANETs). Our proposed framework is mainly divided into four components:
      redundant information, priority assignment, malicious data verification and
      malicious node verification. The proposed scheme jhas been validated with the
      help of the NS-2 network simulator and the Evalvid tool.

PMID- 22163463
TI  - Large lateral photovoltaic effect in metal-(oxide-) semiconductor structures.
AB  - The lateral photovoltaic effect (LPE) can be used in position-sensitive detectors
      to detect very small displacements due to its output of lateral photovoltage
      changing linearly with light spot position. In this review, we will summarize
      some of our recent works regarding LPE in metal-semiconductor and metal-oxide
      semiconductor structures, and give a theoretical model of LPE in these two
      structures.

PMID- 22163464
TI  - Extended target recognition in cognitive radar networks.
AB  - We address the problem of adaptive waveform design for extended target
      recognition in cognitive radar networks. A closed-loop active target recognition
      radar system is extended to the case of a centralized cognitive radar network, in
      which a generalized likelihood ratio (GLR) based sequential hypothesis testing
      (SHT) framework is employed. Using Doppler velocities measured by multiple
      radars, the target aspect angle for each radar is calculated. The joint
      probability of each target hypothesis is then updated using observations from
      different radar line of sights (LOS). Based on these probabilities, a minimum
      correlation algorithm is proposed to adaptively design the transmit waveform for
      each radar in an amplitude fluctuation situation. Simulation results demonstrate
      performance improvements due to the cognitive radar network and adaptive waveform
      design. Our minimum correlation algorithm outperforms the eigen-waveform solution
      and other non-cognitive waveform design approaches.

PMID- 22163465
TI  - Plastic optical fiber displacement sensor based on dual cycling bending.
AB  - In this study, a high sensitivity and easy fabricated plastic optical fiber (POF)
      displacement sensor is proposed. A POF specimen subjected to dual cyclic bending
      is used to improve the sensitivity of the POF displacement sensor. The effects of
      interval between rollers, relative displacement and number of rollers on the
      sensitivity of the displacement sensor are analyzed both experimentally and
      numerically. A good agreement between the experimental measurements and numerical
      calculations is obtained. The results show that the interval between rollers
      affects sensitivity most significantly than the other design parameters. Based on
      the experimental data, a linear equation is derived to estimate the relationship
      between the power loss and the relative displacement. The difference between the
      estimated results and the experimental results is found to be less than 8%. The
      results also show that the proposed POF displacement sensor based on dual cyclic
      bending can be used to detect displacement accurately.

PMID- 22163466
TI  - A polymer-based capacitive sensing array for normal and shear force measurement.
AB  - In this work, we present the development of a polymer-based capacitive sensing
      array. The proposed device is capable of measuring normal and shear forces, and
      can be easily realized by using micromachining techniques and flexible printed
      circuit board (FPCB) technologies. The sensing array consists of a
      polydimethlysiloxane (PDMS) structure and a FPCB. Each shear sensing element
      comprises four capacitive sensing cells arranged in a 2 * 2 array, and each
      capacitive sensing cell has two sensing electrodes and a common floating
      electrode. The sensing electrodes as well as the metal interconnect for signal
      scanning are implemented on the FPCB, while the floating electrodes are patterned
      on the PDMS structure. This design can effectively reduce the complexity of the
      capacitive structures, and thus makes the device highly manufacturable. The
      characteristics of the devices with different dimensions were measured and
      discussed. A scanning circuit was also designed and implemented. The measured
      maximum sensitivity is 1.67%/mN. The minimum resolvable force is 26 mN measured
      by the scanning circuit. The capacitance distributions induced by normal and
      shear forces were also successfully captured by the sensing array.

PMID- 22163467
TI  - Fabrication and performance of all-solid-state chloride sensors in synthetic
      concrete pore solutions.
AB  - One type of all-solid-state chloride sensor was fabricated using a MnO(2)
      electrode and a Ag/AgCl electrode. The potentiometric response of the sensor to
      chloride in synthetic concrete pore solutions was systematically studied, and the
      polarization performance was also evaluated. The results show a good linear
      relationship between the potential reading of the sensor and the logarithm of
      chloride activity (concentration ranges from 0.05 to 5.0 M), and the potential
      value remains stable with increasing immersion time. The existence of K(+),
      Ca(2+), Na(+) and SO(4) (2-) ions have little influence on the potentiometric
      response of the sensor to chloride, but the pH has a significant influence on the
      potential value of the sensor at low chloride concentration. The potential
      reading of the sensor increases linearly with the solution temperature over the
      range from 5 to 45  degrees C. Meanwhile, an excellent polarization behavior is
      proven by galvanostatic and potentiodynamic tests. All of the results reveal that
      the developed sensor has a great potential for monitoring chloride ions in
      concrete environments.

PMID- 22163468
TI  - A wearable ground reaction force sensor system and its application to the
      measurement of extrinsic gait variability.
AB  - Wearable sensors for gait analysis are attracting wide interest. In this paper, a
      wearable ground reaction force (GRF) sensor system and its application to measure
      extrinsic gait variability are presented. To validate the GRF and centre of
      pressure (CoP) measurements of the sensor system and examine the effectiveness of
      the proposed method for gait analysis, we conducted an experimental study on
      seven volunteer subjects. Based on the assessment of the influence of the sensor
      system on natural gait, we found that no significant differences were found for
      almost all measured gait parameters (p-values < 0.05). As for measurement
      accuracy, the root mean square (RMS) differences for the two transverse
      components and the vertical component of the GRF were 7.2% +/- 0.8% and 9.0% +/-
      1% of the maximum of each transverse component and 1.5% +/- 0.9% of the maximum
      vertical component of GRF, respectively. The RMS distance between both CoP
      measurements was 1.4% +/- 0.2% of the length of the shoe. The area of CoP
      distribution on the foot-plate and the average coefficient of variation of the
      triaxial GRF, are the introduced parameters for analysing extrinsic gait
      variability. Based on a statistical analysis of the results of the tests with
      subjects wearing the sensor system, we found that the proposed parameters changed
      according to walking speed and turning (p-values < 0.05).

PMID- 22163469
TI  - An overview of kinematic and calibration models using internal/external sensors
      or constraints to improve the behavior of spatial parallel mechanisms.
AB  - This paper presents an overview of the literature on kinematic and calibration
      models of parallel mechanisms, the influence of sensors in the mechanism accuracy
      and parallel mechanisms used as sensors. The most relevant classifications to
      obtain and solve kinematic models and to identify geometric and non-geometric
      parameters in the calibration of parallel robots are discussed, examining the
      advantages and disadvantages of each method, presenting new trends and
      identifying unsolved problems. This overview tries to answer and show the
      solutions developed by the most up-to-date research to some of the most frequent
      questions that appear in the modelling of a parallel mechanism, such as how to
      measure, the number of sensors and necessary configurations, the type and
      influence of errors or the number of necessary parameters.

PMID- 22163470
TI  - Biocatalysts immobilized in ultrathin ordered films.
AB  - The immobilization of enzymes and other proteins into ordered thin materials has
      attracted considerable attention over the past few years. This research has
      demonstrated that biomolecules immobilized in different [Langmuir-Blodgett
      (LB)/Langmuir-Schaefer (LS)] matrixes retain their functional characteristics to
      a large extent. These new materials are of interest for applications as
      biosensors and biocatalysts. We review the growing field of oxidases immobilized
      onto ordered Langmiur-Blodgett and Langmuir-Schaefer films. Strategies for the
      preparation of solid supports and the essential properties of the resulting
      materials with respect to the envisaged applications are presented. Basic effects
      of the nature of the adsorption and various aspects of the application of these
      materials as biosensors, biocatalysts are discussed. Outlook of potential
      applications and further challenges are also provided.

PMID- 22163471
TI  - A new wireless biosensor for intra-vaginal temperature monitoring.
AB  - Wireless Body Sensors for medical purposes offer valuable contributions to
      improve patients' healthcare, including diagnosis and/or therapeutics monitoring.
      Body temperature is a crucial parameter in healthcare diagnosis. In gynecology
      and obstetrics it is measured at the skin's surface, which is very influenced by
      the environment. This paper proposes a new intra-body sensor for long-term intra
      vaginal temperature collection. The embedded IEEE 802.15.4 communication module
      allows the integration of this sensor in a Wireless Sensor Network (WSN) for
      remote data access and monitoring. We present the sensor architecture, the
      construction of the corresponding testbed, and its performance evaluation. This
      sensor may be used in different medical applications, including preterm labor
      prevention and fertility and ovulation period detection. The features of the
      constructed testbed were validated in laboratory tests verifying its accuracy and
      performance.

PMID- 22163472
TI  - Dynamic load balancing data centric storage for wireless sensor networks.
AB  - In this paper, a new data centric storage that is dynamically adapted to the work
      load changes is proposed. The proposed data centric storage distributes the load
      of hot spot areas to neighboring sensor nodes by using a multilevel grid
      technique. The proposed method is also able to use existing routing protocols
      such as GPSR (Greedy Perimeter Stateless Routing) with small changes. Through
      simulation, the proposed method enhances the lifetime of sensor networks over one
      of the state-of-the-art data centric storages. We implement the proposed method
      based on an operating system for sensor networks, and evaluate the performance
      through running based on a simulation tool.

PMID- 22163473
TI  - Fabrication and characterization of 3D micro- and nanoelectrodes for neuron
      recordings.
AB  - In this paper we discuss the fabrication and characterization of three
      dimensional (3D) micro- and nanoelectrodes with the goal of using them for extra-
      and intracellular studies. Two different types of electrodes will be described:
      high aspect ratio microelectrodes for studying the communication between cells
      and ultimately for brain slice recordings and small nanoelectrodes for highly
      localized measurements and ultimately for intracellular studies. Electrical and
      electrochemical characterization of these electrodes as well as the results of
      PC12 cell differentiation on chip will be presented and discussed.

PMID- 22163474
TI  - A general purpose feature extractor for light detection and ranging data.
AB  - Feature extraction is a central step of processing Light Detection and Ranging
      (LIDAR) data. Existing detectors tend to exploit characteristics of specific
      environments: corners and lines from indoor (rectilinear) environments, and trees
      from outdoor environments. While these detectors work well in their intended
      environments, their performance in different environments can be poor. We
      describe a general purpose feature detector for both 2D and 3D LIDAR data that is
      applicable to virtually any environment. Our method adapts classic feature
      detection methods from the image processing literature, specifically the multi
      scale Kanade-Tomasi corner detector. The resulting method is capable of
      identifying highly stable and repeatable features at a variety of spatial scales
      without knowledge of environment, and produces principled uncertainty estimates
      and corner descriptors at same time. We present results on both software
      simulation and standard datasets, including the 2D Victoria Park and Intel
      Research Center datasets, and the 3D MIT DARPA Urban Challenge dataset.

PMID- 22163475
TI  - Research on a Denial of Service (DoS) detection system based on global
      interdependent behaviors in a sensor network environment.
AB  - This research suggests a Denial of Service (DoS) detection method based on the
      collection of interdependent behavior data in a sensor network environment. In
      order to collect the interdependent behavior data, we use a base station to
      analyze traffic and behaviors among nodes and introduce methods of detecting
      changes in the environment with precursor symptoms. The study presents a DoS
      Detection System based on Global Interdependent Behaviors and shows the result of
      detecting a sensor carrying out DoS attacks through the test-bed.

PMID- 22163476
TI  - Data refinement and channel selection for a portable e-nose system by the use of
      feature feedback.
AB  - We propose a data refinement and channel selection method for vapor
      classification in a portable e-nose system. For the robust e-nose system in a
      real environment, we propose to reduce the noise in the data measured by sensor
      arrays and distinguish the important part in the data by the use of feature
      feedback. Experimental results on different volatile organic compounds data show
      that the proposed data refinement method gives good clustering for different
      classes and improves the classification performance. Also, we design a new sensor
      array that consists only of the useful channels. For this purpose, each channel
      is evaluated by measuring its discriminative power based on the feature mask used
      in the data refinement. Through the experimental results, we show that the new
      sensor array improves both the classification rates and the efficiency in
      computation and data storage.

PMID- 22163477
TI  - Process monitoring evaluation and implementation for the wood abrasive machining
      process.
AB  - Wood processing industries have continuously developed and improved technologies
      and processes to transform wood to obtain better final product quality and thus
      increase profits. Abrasive machining is one of the most important of these
      processes and therefore merits special attention and study. The objective of this
      work was to evaluate and demonstrate a process monitoring system for use in the
      abrasive machining of wood and wood based products. The system developed
      increases the life of the belt by detecting (using process monitoring sensors)
      and removing (by cleaning) the abrasive loading during the machining process.
      This study focused on abrasive belt machining processes and included substantial
      background work, which provided a solid base for understanding the behavior of
      the abrasive, and the different ways that the abrasive machining process can be
      monitored. In addition, the background research showed that abrasive belts can
      effectively be cleaned by the appropriate cleaning technique. The process
      monitoring system developed included acoustic emission sensors which tended to be
      sensitive to belt wear, as well as platen vibration, but not loading, and optical
      sensors which were sensitive to abrasive loading.

PMID- 22163478
TI  - Using a floating-gate MOS transistor as a transducer in a MEMS gas sensing
      system.
AB  - Floating-gate MOS transistors have been widely used in diverse analog and digital
      applications. One of these is as a charge sensitive device in sensors for pH
      measurement in solutions or using gates with metals like Pd or Pt for hydrogen
      sensing. Efforts are being made to monolithically integrate sensors together with
      controlling and signal processing electronics using standard technologies. This
      can be achieved with the demonstrated compatibility between available CMOS
      technology and MEMS technology. In this paper an in-depth analysis is done
      regarding the reliability of floating-gate MOS transistors when charge produced
      by a chemical reaction between metallic oxide thin films with either reducing or
      oxidizing gases is present. These chemical reactions need temperatures around 200
      degrees C or higher to take place, so thermal insulation of the sensing area
      must be assured for appropriate operation of the electronics at room temperature.
      The operation principle of the proposal here presented is confirmed by connecting
      the gate of a conventional MOS transistor in series with a Fe(2)O(3) layer. It is
      shown that an electrochemical potential is present on the ferrite layer when
      reacting with propane.

PMID- 22163479
TI  - Design and implementation of a GPS guidance system for agricultural tractors
      using augmented reality technology.
AB  - Current commercial tractor guidance systems present to the driver information to
      perform agricultural tasks in the best way. This information generally includes a
      treated zones map referenced to the tractor's position. Unlike actual guidance
      systems where the tractor driver must mentally associate treated zone maps and
      the plot layout, this paper presents a guidance system that using Augmented
      Reality (AR) technology, allows the tractor driver to see the real plot though
      eye monitor glasses with the treated zones in a different color. The paper
      includes a description of the system hardware and software, a real test done with
      image captures seen by the tractor driver, and a discussion predicting that the
      historical evolution of guidance systems could involve the use of AR technology
      in the agricultural guidance and monitoring systems.

PMID- 22163480
TI  - An online universal diagnosis procedure using two external flux sensors applied
      to the AC electrical rotating machines.
AB  - This paper presents an original non-invasive procedure for the diagnosis of
      electromagnetic devices, as well as AC electrical rotating machines using two
      external flux coil sensors that measure the external magnetic field in the
      machines' vicinity. The diagnosis exploits the signal delivered by the two
      sensors placed in particular positions. Contrary to classical methods using only
      one sensor, the presented method does not require any knowledge of a presumed
      machine's healthy former state. On the other hand, the loading operating is not a
      disturbing factor but it is used to the fault discrimination. In order to present
      this procedure, an internal stator inter-turn short-circuit fault is considered
      as well.

PMID- 22163481
TI  - A local weighted nearest neighbor algorithm and a weighted and constrained least
      squared method for mixed odor analysis by electronic nose systems.
AB  - A great deal of work has been done to develop techniques for odor analysis by
      electronic nose systems. These analyses mostly focus on identifying a particular
      odor by comparing with a known odor dataset. However, in many situations, it
      would be more practical if each individual odorant could be determined directly.
      This paper proposes two methods for such odor components analysis for electronic
      nose systems. First, a K-nearest neighbor (KNN)-based local weighted nearest
      neighbor (LWNN) algorithm is proposed to determine the components of an odor.
      According to the component analysis, the odor training data is firstly
      categorized into several groups, each of which is represented by its centroid.
      The examined odor is then classified as the class of the nearest centroid. The
      distance between the examined odor and the centroid is calculated based on a
      weighting scheme, which captures the local structure of each predefined group. To
      further determine the concentration of each component, odor models are built by
      regressions. Then, a weighted and constrained least-squares (WCLS) method is
      proposed to estimate the component concentrations. Experiments were carried out
      to assess the effectiveness of the proposed methods. The LWNN algorithm is able
      to classify mixed odors with different mixing ratios, while the WCLS method can
      provide good estimates on component concentrations.

PMID- 22163482
TI  - Photo-detectors for time of flight positron emission tomography (ToF-PET).
AB  - We present the most recent advances in photo-detector design employed in time of
      flight positron emission tomography (ToF-PET). PET is a molecular imaging
      modality that collects pairs of coincident (temporally correlated) annihilation
      photons emitted from the patient body. The annihilation photon detector typically
      comprises a scintillation crystal coupled to a fast photo-detector. ToF
      information provides better localization of the annihilation event along the line
      formed by each detector pair, resulting in an overall improvement in signal to
      noise ratio (SNR) of the reconstructed image. Apart from the demand for high
      luminosity and fast decay time of the scintillation crystal, proper design and
      selection of the photo-detector and methods for arrival time pick-off are a
      prerequisite for achieving excellent time resolution required for ToF-PET. We
      review the two types of photo-detectors used in ToF-PET: photomultiplier tubes
      (PMTs) and silicon photo-multipliers (SiPMs) with a special focus on SiPMs.

PMID- 22163483
TI  - A comparative study of wireless sensor networks and their routing protocols.
AB  - Recent developments in the area of micro-sensor devices have accelerated advances
      in the sensor networks field leading to many new protocols specifically designed
      for wireless sensor networks (WSNs). Wireless sensor networks with hundreds to
      thousands of sensor nodes can gather information from an unattended location and
      transmit the gathered data to a particular user, depending on the application.
      These sensor nodes have some constraints due to their limited energy, storage
      capacity and computing power. Data are routed from one node to other using
      different routing protocols. There are a number of routing protocols for wireless
      sensor networks. In this review article, we discuss the architecture of wireless
      sensor networks. Further, we categorize the routing protocols according to some
      key factors and summarize their mode of operation. Finally, we provide a
      comparative study on these various protocols.

PMID- 22163484
TI  - Optimal and robust design method for two-chip out-of-plane microaccelerometers.
AB  - In this paper, an optimal and robust design method to implement a two-chip out-of
      plane microaccelerometer system is presented. The two-chip microsystem consists
      of a MEMS chip for sensing the external acceleration and a CMOS chip for signal
      processing. An optimized design method to determine the device thickness, the
      sacrificial gap, and the vertical gap length of the M EMS sensing element is
      applied to minimize the fundamental noise level and also to achieve the
      robustness to the fabrication variations. In order to cancel out the offset and
      gain variations due to parasitic capacitances and process variations, a digitally
      trimmable architecture consisting of an 11 bit capacitor array is adopted in the
      analog front-end of the CMOS capacitive readout circuit. The out-of-plane
      microaccelerometer has the scale factor of 372 mV/g~389 mV/g, the output
      nonlinearity of 0.43% FSO~0.60% FSO, the input range of +/-2 g and a bias
      instability of 122 MUg~229 MUg. The signal-to-noise ratio and the noise
      equivalent resolution are measured to be 74.00 dB~75.23 dB and 180 MUg/rtHz~190
      MUg/rtHz, respectively. The in-plane cross-axis sensitivities are measured to be
      1.1%~1.9% and 0.3%~0.7% of the out-of-plane sensitivity, respectively. The
      results show that the optimal and robust design method for the MEMS sensing
      element and the highly trimmable capacity of the CMOS capacitive readout circuit
      are suitable to enhance the die-to-die uniformity of the packaged microsystem,
      without compromising the performance characteristics.

PMID- 22163485
TI  - Model-free adaptive sensing and control for a piezoelectrically actuated system.
AB  - Since the piezoelectrically actuated system has nonlinear and time-varying
      behavior, it is difficult to establish an accurate dynamic model for a model
      based sensing and control design. Here, a model-free adaptive sliding controller
      is proposed to improve the small travel and hysteresis defects of
      piezoelectrically actuated systems. This sensing and control strategy employs the
      functional approximation technique (FAT) to establish the unknown function for
      eliminating the model-based requirement of the sliding-mode control. The
      piezoelectrically actuated system's nonlinear functions can be approximated by
      using the combination of a finite number of weighted Fourier series basis
      functions. The unknown weighted vector can be estimated by an updating rule. The
      important advantage of this approach is to achieve the sliding-mode controller
      design without the system dynamic model requirement. The update laws for the
      coefficients of the Fourier series functions are derived from a Lyapunov function
      to guarantee the control system stability. This proposed controller is
      implemented on a piezoelectrically actuated X-Y table. The dynamic experimental
      result of this proposed FAT controller is compared with that of a traditional
      model-based sliding-mode controller to show the performance improvement for the
      motion tracking performance.

PMID- 22163486
TI  - A new approach to laminar flowmeters.
AB  - After studying the performance and characteristics of actual laminar flowmeters a
      new disposition for this type of sensors is proposed in such a way that the
      measurement errors introduced by the intrinsic nature of the device can be
      minimized. The preliminary study shows that the developing entry region
      introduces non-linearity effects in all these devices. These effects bring about
      not only errors, but also a change in the slope of the linear calibration respect
      of the Poiseuille relation. After a subsequent analysis on how these non
      linearity errors can be reduced, a new disposition of this type of flowmeters is
      introduced. This device makes used of flow elements having pressure taps at three
      locations along its length and connected to three isolated chambers. In this way,
      the static pressure can be measured at three locations and contributed to by the
      pressure taps at the level of each chamber. Thus the linearization error is
      reduced with an additional advantage of producing a reduced pressure drop.

PMID- 22163487
TI  - Near-infrared sub-bandgap all-silicon photodetectors: state of the art and
      perspectives.
AB  - Due to recent breakthroughs, silicon photonics is now the most active discipline
      within the field of integrated optics and, at the same time, a present reality
      with commercial products available on the market. Silicon photodiodes are
      excellent detectors at visible wavelengths, but the development of high
      performance photodetectors on silicon CMOS platforms at wavelengths of interest
      for telecommunications has remained an imperative but unaccomplished task so far.
      In recent years, however, a number of near-infrared all-silicon photodetectors
      have been proposed and demonstrated for optical interconnect and power-monitoring
      applications. In this paper, a review of the state of the art is presented.
      Devices based on mid-bandgap absorption, surface-state absorption, internal
      photoemission absorption and two-photon absorption are reported, their working
      principles elucidated and their performance discussed and compared.

PMID- 22163488
TI  - Automated detection of the arterial inner walls of the common carotid artery
      based on dynamic B-mode signals.
AB  - In this paper we propose a novel scheme able to automatically detect the intima
      and adventitia of both near and far walls of the common carotid artery in dynamic
      B-mode RF (radiofrequency) image sequences, with and without plaques. Via this
      automated system the lumen diameter changes along the heart cycle can be
      detected. Three image sequences have been tested and all results are compared to
      manual tracings made by two professional experts. The average errors for near and
      far wall detection are 0.058 mm and 0.067 mm, respectively. This system is able
      to analyze arterial plaques dynamically which is impossible to do manually due to
      the tremendous human workload involved.

PMID- 22163489
TI  - Transport infrastructure surveillance and monitoring by electromagnetic sensing:
      the ISTIMES project.
AB  - The ISTIMES project, funded by the European Commission in the frame of a joint
      Call "ICT and Security" of the Seventh Framework Programme, is presented and
      preliminary research results are discussed. The main objective of the ISTIMES
      project is to design, assess and promote an Information and Communication
      Technologies (ICT)-based system, exploiting distributed and local sensors, for
      non-destructive electromagnetic monitoring of critical transport infrastructures.
      The integration of electromagnetic technologies with new ICT information and
      telecommunications systems enables remotely controlled monitoring and
      surveillance and real time data imaging of the critical transport
      infrastructures. The project exploits different non-invasive imaging technologies
      based on electromagnetic sensing (optic fiber sensors, Synthetic Aperture Radar
      satellite platform based, hyperspectral spectroscopy, Infrared thermography,
      Ground Penetrating Radar-, low-frequency geophysical techniques, Ground based
      systems for displacement monitoring). In this paper, we show the preliminary
      results arising from the GPR and infrared thermographic measurements carried out
      on the Musmeci bridge in Potenza, located in a highly seismic area of the
      Apennine chain (Southern Italy) and representing one of the test beds of the
      project.

PMID- 22163490
TI  - A server-based mobile coaching system.
AB  - A prototype system for monitoring, transmitting and processing performance data
      in sports for the purpose of providing feedback has been developed. During
      training, athletes are equipped with a mobile device and wireless sensors using
      the ANT protocol in order to acquire biomechanical, physiological and other
      sports specific parameters. The measured data is buffered locally and forwarded
      via the Internet to a server. The server provides experts (coaches,
      biomechanists, sports medicine specialists etc.) with remote data access,
      analysis and (partly automated) feedback routines. In this way, experts are able
      to analyze the athlete's performance and return individual feedback messages from
      remote locations.

PMID- 22163491
TI  - The use of Helmholtz resonance for measuring the volume of liquids and solids.
AB  - An experimental investigation was undertaken to ascertain the potential of using
      Helmholtz resonance for volume determination and the factors that may influence
      accuracy. The uses for a rapid non-interference volume measurement system range
      from agricultural produce and mineral sampling through to liquid fill
      measurements. By weighing the sample the density can also measured indirectly.

PMID- 22163492
TI  - A compact vertical scanner for atomic force microscopes.
AB  - A compact vertical scanner for an atomic force microscope (AFM) is developed. The
      vertical scanner is designed to have no interference with the optical microscope
      for viewing the cantilever. The theoretical stiffness and resonance of the
      scanner are derived and verified via finite element analysis. An optimal design
      process that maximizes the resonance frequency is performed. To evaluate the
      scanner's performance, experiments are performed to evaluate the travel range,
      resonance frequency, and feedback noise level. In addition, an AFM image using
      the proposed vertical scanner is generated.

PMID- 22163493
TI  - Wall-corner classification using sonar: a new approach based on geometric
      features.
AB  - Ultrasonic signals coming from rotary sonar sensors in a robot gives us several
      features about the environment. This enables us to locate and classify the
      objects in the scenario of the robot. Each object and reflector produces a series
      of peaks in the amplitude of the signal. The radial and angular position of the
      sonar sensor gives information about location and their amplitudes offer
      information about the nature of the surface. Early works showed that the
      amplitude can be modeled and used to classify objects with very good results at
      short distances-80% average success in classifying both walls and corners at
      distances less than 1.5 m. In this paper, a new set of geometric features derived
      from the amplitude analysis of the echo is presented. These features constitute a
      set of characteristics that can be used to improve the results of classification
      at distances from 1.5 m to 4 m. Also, a comparative study on classification
      algorithms widely used in pattern recognition techniques has been carried out for
      sensor distances ranging between 0.5 to 4 m, and with incidence angles ranging
      between 20 degrees  to 70 degrees . Experimental results show an enhancement on
      the success in classification rates when these geometric features are considered.

PMID- 22163494
TI  - Fabrication of a flexible micro CO sensor for micro reformer applications.
AB  - Integration of a reformer and a proton exchange membrane fuel cell (PEMFC) is
      problematic due to the presence in the gas from the reforming process of a slight
      amount of carbon monoxide. Carbon monoxide poisons the catalyst of the proton
      exchange membrane fuel cell subsequently degrading the fuel cell performance, and
      necessitating the sublimation of the reaction gas before supplying to fuel cells.
      Based on the use of micro-electro-mechanical systems (MEMS) technology to
      manufacture flexible micro CO sensors, this study elucidates the relation between
      a micro CO sensor and different SnO2 thin film thicknesses. Experimental results
      indicate that the sensitivity increases at temperatures ranging from 100-300 
      degrees C. Additionally, the best sensitivity is obtained at a specific
      temperature. For instance, the best sensitivity of SnO2 thin film thickness of
      100 nm at 300  degrees C is 59.3%. Moreover, a flexible micro CO sensor is
      embedded into a micro reformer to determine the CO concentration in each part of
      a micro reformer in the future, demonstrating the inner reaction of a micro
      reformer in depth and immediate detection.

PMID- 22163495
TI  - A low cost device for monitoring the urine output of critical care patients.
AB  - In critical care units most of the patients' physiological parameters are sensed
      by commercial monitoring devices. These devices can also supervise whether the
      values of the parameters lie within a pre-established range set by the clinician.
      The automation of the sensing and supervision tasks has discharged the healthcare
      staff of a considerable workload and avoids human errors, which are common in
      repetitive and monotonous tasks. Urine output is very likely the most relevant
      physiological parameter that has yet to be sensed or supervised automatically.
      This paper presents a low cost patent-pending device capable of sensing and
      supervising urine output. The device uses reed switches activated by a magnetic
      float in order to measure the amount of urine collected in two containers which
      are arranged in cascade. When either of the containers fills, it is emptied
      automatically using a siphon mechanism and urine begins to collect again. An
      electronic unit sends the state of the reed switches via Bluetooth to a PC that
      calculates the urine output from this information and supervises the achievement
      of therapeutic goals.

PMID- 22163496
TI  - Upper limb portable motion analysis system based on inertial technology for
      neurorehabilitation purposes.
AB  - Here an inertial sensor-based monitoring system for measuring and analyzing upper
      limb movements is presented. The final goal is the integration of this motion
      tracking device within a portable rehabilitation system for brain injury
      patients. A set of four inertial sensors mounted on a special garment worn by the
      patient provides the quaternions representing the patient upper limb's
      orientation in space. A kinematic model is built to estimate 3D upper limb motion
      for accurate therapeutic evaluation. The human upper limb is represented as a
      kinematic chain of rigid bodies with three joints and six degrees of freedom.
      Validation of the system has been performed by co-registration of movements with
      a commercial optoelectronic tracking system. Successful results are shown that
      exhibit a high correlation among signals provided by both devices and obtained at
      the Institut Guttmann Neurorehabilitation Hospital.

PMID- 22163497
TI  - Study of the ubiquitous hog farm system using wireless sensor networks for
      environmental monitoring and facilities control.
AB  - Many hog farmers are now suffering from high pig mortality rates due to various
      wasting diseases and increased breeding costs, etc. It is therefore necessary for
      hog farms to implement systematic and scientific pig production technology to
      increase productivity and produce high quality pork in order to solve these
      problems. In this study, we describe such a technology by suggesting a ubiquitous
      hog farm system which applies WSN (Wireless Sensor Network) technology to the pig
      industry. We suggest that a WSN and CCTV (Closed-circuit television) should be
      installed on hog farms to collect environmental and image information which shall
      then help producers not only in monitoring the hog farm via the Web from outside
      the farm, but also facilitate the control of hog farm facilities in remote
      locations. In addition, facilities can be automatically controlled based on
      breeding environment parameters which are already set up and a SMS notice service
      to notify of deviations shall provide users with convenience. Hog farmers may
      increase production and improve pork quality through this ubiquitous hog farm
      system and prepare a database with information collected from environmental
      factors and the hog farm control devices, which is expected to provide
      information needed to design and implement suitable control strategies for hog
      farm operation.

PMID- 22163498
TI  - Ultra-wideband sensors for improved magnetic resonance imaging, cardiovascular
      monitoring and tumour diagnostics.
AB  - The specific advantages of ultra-wideband electromagnetic remote sensing (UWB
      radar) make it a particularly attractive technique for biomedical applications.
      We partially review our activities in utilizing this novel approach for the
      benefit of high and ultra-high field magnetic resonance imaging (MRI) and other
      applications, e.g., for intensive care medicine and biomedical research. We could
      show that our approach is beneficial for applications like motion tracking for
      high resolution brain imaging due to the non-contact acquisition of involuntary
      head motions with high spatial resolution, navigation for cardiac MRI due to our
      interpretation of the detected physiological mechanical contraction of the heart
      muscle and for MR safety, since we have investigated the influence of high static
      magnetic fields on myocardial mechanics. From our findings we could conclude,
      that UWB radar can serve as a navigator technique for high and ultra-high field
      magnetic resonance imaging and can be beneficial preserving the high resolution
      capability of this imaging modality. Furthermore it can potentially be used to
      support standard ECG analysis by complementary information where sole ECG
      analysis fails. Further analytical investigations have proven the feasibility of
      this method for intracranial displacements detection and the rendition of a
      tumour's contrast agent based perfusion dynamic. Beside these analytical
      approaches we have carried out FDTD simulations of a complex arrangement
      mimicking the illumination of a human torso model incorporating the geometry of
      the antennas applied.

PMID- 22163499
TI  - Evaluation of high-precision sensors in structural monitoring.
AB  - One of the most intricate branches of metrology involves the monitoring of
      displacements and deformations of natural and anthropogenic structures under
      environmental forces, such as tidal or tectonic phenomena, or ground water level
      changes. Technological progress has changed the measurement process, and steadily
      increasing accuracy requirements have led to the continued development of new
      measuring instruments. The adoption of an appropriate measurement strategy, with
      proper instruments suited for the characteristics of the observed structure and
      its environmental conditions, is of high priority in the planning of deformation
      monitoring processes. This paper describes the use of precise digital inclination
      sensors in continuous monitoring of structural deformations. The topic is treated
      from two viewpoints: (i) evaluation of the performance of inclination sensors by
      comparing them to static and continuous GPS observations in deformation
      monitoring and (ii) providing a strategy for analyzing the structural
      deformations. The movements of two case study objects, a tall building and a
      geodetic monument in Istanbul, were separately monitored using dual-axes micro
      radian precision inclination sensors (inclinometers) and GPS. The time series of
      continuous deformation observations were analyzed using the Least Squares
      Spectral Analysis Technique (LSSA). Overall, the inclinometers showed good
      performance for continuous monitoring of structural displacements, even at the
      sub-millimeter level. Static GPS observations remained insufficient for resolving
      the deformations to the sub-centimeter level due to the errors that affect GPS
      signals. With the accuracy advantage of inclination sensors, their use with GPS
      provides more detailed investigation of deformation phenomena. Using
      inclinometers and GPS is helpful to be able to identify the components of
      structural responses to the natural forces as static, quasi-static, or resonant.

PMID- 22163500
TI  - Generalization of DT equations for time dependent sources.
AB  - New equations for paralyzable, non paralyzable and hybrid DT models, valid for
      any time dependent sources are presented. We show how such new equations include
      the equations already used for constant rate sources, and how it's is possible to
      correct DT losses in the case of time dependent sources. Montecarlo simulations
      were performed to compare the equations behavior with the three DT models.
      Excellent accordance between equations predictions and Montecarlo simulation was
      found. We also obtain good results in the experimental validation of the new
      hybrid DT equation. Passive quenched SPAD device was chosen as a device affected
      by hybrid DT losses and active quenched SPAD with 50 ns DT was used as DT losses
      free device.

PMID- 22163501
TI  - Detecting vital signs with wearable wireless sensors.
AB  - The emergence of wireless technologies and advancements in on-body sensor design
      can enable change in the conventional health-care system, replacing it with
      wearable health-care systems, centred on the individual. Wearable monitoring
      systems can provide continuous physiological data, as well as better information
      regarding the general health of individuals. Thus, such vital-sign monitoring
      systems will reduce health-care costs by disease prevention and enhance the
      quality of life with disease management. In this paper, recent progress in non
      invasive monitoring technologies for chronic disease management is reviewed. In
      particular, devices and techniques for monitoring blood pressure, blood glucose
      levels, cardiac activity and respiratory activity are discussed; in addition, on
      body propagation issues for multiple sensors are presented.

PMID- 22163502
TI  - Reflectively coupled waveguide photodetector for high speed optical
      interconnection.
AB  - To fully utilize GaAs high drift mobility, techniques to monolithically integrate
      In0.53Ga0.47As p-i-n photodetectors with GaAs based optical waveguides using
      total internal reflection coupling are reviewed. Metal coplanar waveguides,
      deposited on top of the polyimide layer for the photodetector's planarization and
      passivation, were then uniquely connected as a bridge between the photonics and
      electronics to illustrate the high-speed monitoring function. The photodetectors
      were efficiently implemented and imposed on the echelle grating circle for
      wavelength division multiplexing monitoring. In optical filtering performance,
      the monolithically integrated photodetector channel spacing was 2 nm over the
      1,520-1,550 nm wavelength range and the pass band was 1 nm at the -1 dB level.
      For high-speed applications the full-width half-maximum of the temporal response
      and 3-dB bandwidth for the reflectively coupled waveguide photodetectors were
      demonstrated to be 30 ps and 11 GHz, respectively. The bit error rate performance
      of this integrated photodetector at 10 Gbit/s with 2(7)-1 long pseudo-random bit
      sequence non-return to zero input data also showed error-free operation.

PMID- 22163503
TI  - Modeling the energy performance of event-driven wireless sensor network by using
      static sink and mobile sink.
AB  - Wireless Sensor Networks (WSNs) designed for mission-critical applications suffer
      from limited sensing capacities, particularly fast energy depletion. Regarding
      this, mobile sinks can be used to balance the energy consumption in WSNs, but the
      frequent location updates of the mobile sinks can lead to data collisions and
      rapid energy consumption for some specific sensors. This paper explores an
      optimal barrier coverage based sensor deployment for event driven WSNs where a
      dual-sink model was designed to evaluate the energy performance of not only
      static sensors, but Static Sink (SS) and Mobile Sinks (MSs) simultaneously, based
      on parameters such as sensor transmission range r and the velocity of the mobile
      sink v, etc. Moreover, a MS mobility model was developed to enable SS and MSs to
      effectively collaborate, while achieving spatiotemporal energy performance
      efficiency by using the knowledge of the cumulative density function (cdf),
      Poisson process and M/G/1 queue. The simulation results verified that the
      improved energy performance of the whole network was demonstrated clearly and our
      eDSA algorithm is more efficient than the static-sink model, reducing energy
      consumption approximately in half. Moreover, we demonstrate that our results are
      robust to realistic sensing models and also validate the correctness of our
      results through extensive simulations.

PMID- 22163505
TI  - Estimating plasma glucose from interstitial glucose: the issue of calibration
      algorithms in commercial continuous glucose monitoring devices.
AB  - Evaluation of metabolic control of diabetic people has been classically performed
      measuring glucose concentrations in blood samples. Due to the potential
      improvement it offers in diabetes care, continuous glucose monitoring (CGM) in
      the subcutaneous tissue is gaining popularity among both patients and physicians.
      However, devices for CGM measure glucose concentration in compartments other than
      blood, usually the interstitial space. This means that CGM need calibration
      against blood glucose values, and the accuracy of the estimation of blood glucose
      will also depend on the calibration algorithm. The complexity of the relationship
      between glucose dynamics in blood and the interstitial space, contrasts with the
      simplistic approach of calibration algorithms currently implemented in commercial
      CGM devices, translating in suboptimal accuracy. The present review will analyze
      the issue of calibration algorithms for CGM, focusing exclusively on the
      commercially available glucose sensors.

PMID- 22163506
TI  - Multi-sensor person following in low-visibility scenarios.
AB  - Person following with mobile robots has traditionally been an important research
      topic. It has been solved, in most cases, by the use of machine vision or laser
      rangefinders. In some special circumstances, such as a smoky environment, the use
      of optical sensors is not a good solution. This paper proposes and compares
      alternative sensors and methods to perform a person following in low visibility
      conditions, such as smoky environments in firefighting scenarios. The use of
      laser rangefinder and sonar sensors is proposed in combination with a vision
      system that can determine the amount of smoke in the environment. The smoke
      detection algorithm provides the robot with the ability to use a different
      combination of sensors to perform robot navigation and person following depending
      on the visibility in the environment.

PMID- 22163504
TI  - Monitoring the depth of anaesthesia.
AB  - One of the current challenges in medicine is monitoring the patients' depth of
      general anaesthesia (DGA). Accurate assessment of the depth of anaesthesia
      contributes to tailoring drug administration to the individual patient, thus
      preventing awareness or excessive anaesthetic depth and improving patients'
      outcomes. In the past decade, there has been a significant increase in the number
      of studies on the development, comparison and validation of commercial devices
      that estimate the DGA by analyzing electrical activity of the brain (i.e., evoked
      potentials or brain waves). In this paper we review the most frequently used
      sensors and mathematical methods for monitoring the DGA, their validation in
      clinical practice and discuss the central question of whether these approaches
      can, compared to other conventional methods, reduce the risk of patient awareness
      during surgical procedures.

PMID- 22163507
TI  - A review of direct neck measurement in occupational settings.
AB  - No guidelines are available to orient researchers on the availability and
      applications of equipment and sensors for recording precise neck movements in
      occupational settings. In this study reports on direct measurements of neck
      movements in the workplace were reviewed. Using relevant keywords two independent
      reviewers searched for eligible studies in the following databases: Cinahal,
      Cochrane, Embase, Lilacs, PubMed, MEDLINE, PEDro, Scopus and Web of Science.
      After applying the inclusion criteria, 13 articles on direct neck measurements in
      occupational settings were retrieved from among 33,666 initial titles. These
      studies were then methodologically evaluated according to their design
      characteristics, exposure and outcome assessment, and statistical analysis. The
      results showed that in most of the studies the three axes of neck movement
      (flexion-extension, lateral flexion and rotation) were not simultaneously
      recorded. Deficiencies in available equipment explain this flaw, demonstrating
      that sensors and systems need to be improved so that a true understanding of real
      occupational exposure can be achieved. Further studies are also needed to assess
      neck movement in those who perform heavy-duty work, such as nurses and
      electricians, since no report about such jobs was identified.

PMID- 22163508
TI  - Conducting polymer 3D microelectrodes.
AB  - Conducting polymer 3D microelectrodes have been fabricated for possible future
      neurological applications. A combination of micro-fabrication techniques and
      chemical polymerization methods has been used to create pillar electrodes in
      polyaniline and polypyrrole. The thin polymer films obtained showed uniformity
      and good adhesion to both horizontal and vertical surfaces. Electrodes in
      combination with metal/conducting polymer materials have been characterized by
      cyclic voltammetry and the presence of the conducting polymer film has shown to
      increase the electrochemical activity when compared with electrodes coated with
      only metal. An electrochemical characterization of gold/polypyrrole electrodes
      showed exceptional electrochemical behavior and activity. PC12 cells were finally
      cultured on the investigated materials as a preliminary biocompatibility
      assessment. These results show that the described electrodes are possibly
      suitable for future in-vitro neurological measurements.

PMID- 22163509
TI  - On the relevance of using Bayesian belief networks in wireless sensor networks
      situation recognition.
AB  - Achieving situation recognition in ubiquitous sensor networks (USNs) is an
      important issue that has been poorly addressed by both the research and
      practitioner communities. This paper describes some steps taken to address this
      issue by effecting USN middleware intelligence using an emerging situation
      awareness (ESA) technology. We propose a situation recognition framework where
      temporal probabilistic reasoning is used to derive and emerge situation awareness
      in ubiquitous sensor networks. Using data collected from an outdoor environment
      monitoring in the city of Cape Town, we illustrate the use of the ESA technology
      in terms of sensor system operating conditions and environmental situation
      recognition.

PMID- 22163510
TI  - Performance analysis of receive diversity in wireless sensor networks over GBSBE
      models.
AB  - Wireless sensor networks have attracted a lot of attention recently. In this
      paper, we develop a channel model based on the elliptical model for multipath
      components involving randomly placed scatterers in the scattering region with
      sensors deployed on a field. We verify that in a sensor network, the use of
      receive diversity techniques improves the performance of the system. Extensive
      performance analysis of the system is carried out for both single and multiple
      antennas with the applied receive diversity techniques. Performance analyses
      based on variations in receiver height, maximum multipath delay and transmit
      power have been performed considering different numbers of antenna elements
      present in the receiver array, Our results show that increasing the number of
      antenna elements for a wireless sensor network does indeed improve the BER rates
      that can be obtained.

PMID- 22163511
TI  - Optimal waveforms design for ultra-wideband impulse radio sensors.
AB  - Ultra-wideband impulse radio (UWB-IR) sensors should comply entirely with the
      regulatory spectral limits for elegant coexistence. Under this premise, it is
      desirable for UWB pulses to improve frequency utilization to guarantee the
      transmission reliability. Meanwhile, orthogonal waveform division multiple-access
      (WDMA) is significant to mitigate mutual interferences in UWB sensor networks.
      Motivated by the considerations, we suggest in this paper a low complexity pulse
      forming technique, and its efficient implementation on DSP is investigated. The
      UWB pulse is derived preliminarily with the objective of minimizing the mean
      square error (MSE) between designed power spectrum density (PSD) and the emission
      mask. Subsequently, this pulse is iteratively modified until its PSD completely
      conforms to spectral constraints. The orthogonal restriction is then analyzed and
      different algorithms have been presented. Simulation demonstrates that our
      technique can produce UWB waveforms with frequency utilization far surpassing the
      other existing signals under arbitrary spectral mask conditions. Compared to
      other orthogonality design schemes, the designed pulses can maintain mutual
      orthogonality without any penalty on frequency utilization, and hence, are much
      superior in a WDMA network, especially with synchronization deviations.

PMID- 22163512
TI  - Surface-enhanced Raman scattering sensor on an optical fiber probe fabricated
      with a femtosecond laser.
AB  - A novel fabrication method for surface-enhanced Raman scattering (SERS) sensors
      that used a fast femtosecond (fs) laser scanning process to etch uniform patterns
      and structures on the endface of a fused silica optical fiber, which is then
      coated with a thin layer of silver through thermal evaporation is presented. A
      high quality SERS signal was detected on the patterned surface using a Rhodamine
      6G (Rh6G) solution. The uniform SERS sensor built on the tip of the optical fiber
      tip was small, light weight, and could be especially useful in remote sensing
      applications.

PMID- 22163513
TI  - Scaling up semi-arid grassland biochemical content from the leaf to the canopy
      level: challenges and opportunities.
AB  - Remote sensing imagery is being used intensively to estimate the biochemical
      content of vegetation (e.g., chlorophyll, nitrogen, and lignin) at the leaf
      level. As a result of our need for vegetation biochemical information and our
      increasing ability to obtain canopy spectral data, a few techniques have been
      explored to scale leaf-level biochemical content to the canopy level for forests
      and crops. However, due to the contribution of non-green materials (i.e.,
      standing dead litter, rock, and bare soil) from canopy spectra in semi-arid
      grasslands, it is difficult to obtain information about grassland biochemical
      content from remote sensing data at the canopy level. This paper summarizes
      available methods used to scale biochemical information from the leaf level to
      the canopy level and groups these methods into three categories: direct
      extrapolation, canopy-integrated approach, and inversion of physical models. As
      for semi-arid heterogeneous grasslands, we conclude that all methods are useful,
      but none are ideal. It is recommended that future research should explore a
      systematic upscaling framework which combines spatial pattern analysis, canopy
      integrated approach, and modeling methods to retrieve vegetation biochemical
      content at the canopy level.

PMID- 22163514
TI  - Low-cost electronic microwave calibration for rapid on-line moisture sensing of
      seedcotton.
AB  - In order to improve rapid on-line moisture sensing of seedcotton in cotton gins,
      a means by which to establish a reliable low-cost wide-band electronic
      calibration is critically needed. This calibration is needed to center the
      circuit due to changes in the internal signal delays and attenuation drift caused
      by temperature changes in the various system components and circuit elements.
      This research examines a hardware technique for use in conjunction with microwave
      reflective sensing probes having an extended bandwidth from 500 MHz through 2.5
      GHz. This new technique was validated experimentally against known electrical
      propagation delay standards. Results of the measured propagation delay with this
      type of automatic electronic calibration method was found to agree with results
      using a vector network analyzer with a traditional S11 single port error
      correction calibration methodology to within 4% of the measurement, 95%
      confidence, with a standard error of +/-18.6 ps for the delay measurements. At
      this level of performance, the proposed low-cost technique exhibits superior
      performance, over the typical geosciences time-domain reflectometer "TDR",
      instruments in common use in soil moisture testing and is suitable for use in
      cotton gin moisture sensing.

PMID- 22163516
TI  - Evaluation of mechanical tomato harvesting using wireless sensors.
AB  - The harvesting of processing tomatoes is fully mechanised and it is well known
      that during harvest, fruits are subjected to mechanical stress causing physical
      injuries, including skin punctures, pulp and cell rupture. Some wireless sensors
      have been used for research during recent years with the main purpose of reducing
      the quality loss of tomato fruits by diminishing the number and intensity of
      impacts. In this study the IRD (impact recorder device) sensor was used to
      evaluate several tomato harvesters. The specific objectives were to evaluate the
      impacts during mechanical harvest using a wireless sensor, to determine the
      critical points at which damage occurs, and to assess the damage levels. Samples
      were taken to determine the influence of mechanical harvest on texture, or on
      other quality characteristics including percentage of damages. From the obtained
      data it has been possible to identify the critical points where the damages were
      produced for each one of the five harvester models examined. The highest risk of
      damage was in zone 1 of the combine--from the cutting system to the colour
      selector--because the impacts were of higher intensity and hit less absorbing
      surfaces than in zone 2--from colour selector to discharge. The shaker and exit
      from the shaker are two of the harvester elements that registered the highest
      intensity impacts. By adjusting, in a specific way each harvester model, using
      the results from this research, it has been possible to reduce the tomato damage
      percentage from 20 to 29% to less than 10%.

PMID- 22163515
TI  - Man-machine interface system for neuromuscular training and evaluation based on
      EMG and MMG signals.
AB  - This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training
      System), a multifunction and portable Neuromuscular Training System. The UVa-NTS
      is designed to analyze the voluntary control of severe neuromotor handicapped
      patients, their interactive response, and their adaptation to neuromuscular
      interface systems, such as neural prostheses or domotic applications. Thus, it is
      an excellent tool to evaluate the residual muscle capabilities in the
      handicapped. The UVa-NTS is composed of a custom signal conditioning front-end
      and a computer. The front-end electronics is described thoroughly as well as the
      overall features of the custom software implementation. The software system is
      composed of a set of graphical training tools and a processing core. The UVa-NTS
      works with two classes of neuromuscular signals: the classic myoelectric signals
      (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the
      performance of the processing core, a complete analysis has been done to classify
      its efficiency and to check that it fulfils with the real-time constraints. Tests
      were performed both with healthy and selected impaired subjects. The adaptation
      was achieved rapidly, applying a predefined protocol for the UVa-NTS set of
      training tools. Fine voluntary control was demonstrated to be reached with the
      myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory
      voluntary control when applying the myomechanic signals.

PMID- 22163517
TI  - Colorimetric assay for determination of lead (II) based on its incorporation into
      gold nanoparticles during their synthesis.
AB  - In this report, we present a new method for visual detection of Pb2+. Gold
      nanoparticles (Au-NPs) were synthesized in one step at room temperature, using
      gallic acid (GA) as reducer and stabilizer. Pb2+ is added during the gold
      nanoparticle formation. Analysis of Pb2+ is conducted by a dual strategy, namely,
      colorimetry and spectrometry. During Au-NPs synthesis, addition of Pb2+ would
      lead to formation of Pb-GA complex, which can induce the aggregation of newly
      formed small unstable gold nanoclusters. Consequently, colorimetric detection of
      trace Pb2+ can be realized. As the Pb2+ concentration increases, the color turns
      from red-wine to purple, and finally blue. This method offers a sensitive linear
      correlation between the shift of the absorption band (Deltalambda) and logarithm
      of Pb2+ concentration ranging from 5.0*10(-8) to 1.0*10(-6) M with a linear fit
      coefficient of 0.998, and a high selectivity for Pb2+ detection with a low
      detection limit down to 2.5*10(-8) M.

PMID- 22163518
TI  - Integrated LTCC pressure/flow/temperature multisensor for compressed air
      diagnostics.
AB  - We present a multisensor designed for industrial compressed air diagnostics and
      combining the measurement of pressure, flow, and temperature, integrated with the
      corresponding signal conditioning electronics in a single low-temperature co
      fired ceramic (LTCC) package. The developed sensor may be soldered onto an
      integrated electro-fluidic platform by using standard surface mount device (SMD)
      technology, e.g., as a standard electronic component would be on a printed
      circuit board, obviating the need for both wires and tubes and thus paving the
      road towards low-cost integrated electro-fluidic systems. Several performance
      aspects of this device are presented and discussed, together with electronics
      design issues.

PMID- 22163519
TI  - An optical fiber viscometer based on long-period fiber grating technology and
      capillary tube mechanism.
AB  - This work addresses the development and assessment of a fiber optical viscometer
      using a simple and low-cost long-period fiber grating (LPFG) level sensor and a
      capillary tube mechanism. Previous studies of optical viscosity sensors were
      conducted by using different optical sensing methods. The proposed optical
      viscometer consists of an LPFG sensor, a temperature-controlled chamber, and a
      cone-shaped reservoir where gravitational force could cause fluid to flow through
      the capillary tube. We focused on the use of LPFGs as level sensors and the
      wavelength shifts were not used to quantify the viscosity values of asphalt
      binders. When the LPFG sensor was immersed in the constant volume (100 mL) AC-20
      asphalt binder, a wavelength shift was observed and acquired using LabVIEW
      software and GPIB controller. The time spent between empty and 100 mL was
      calculated to determine the discharge time. We simultaneously measured the LPFG
      induced discharge time and the transmission spectra both in hot air and AC-20
      asphalt binder at five different temperatures, 60, 80, 100, 135, and 170 Celsius.
      An electromechanical rotational viscometer was also used to measure the
      viscosities, 0.15-213.80 Pa.s, of the same asphalt binder at the above five
      temperatures. A non-linear regression analysis was performed to convert LPFG
      induced discharge time into viscosities. Comparative analysis shows that the LPFG
      induced discharge time agreed well with the viscosities obtained from the
      rotational viscometer.

PMID- 22163520
TI  - Study on an agricultural environment monitoring server system using Wireless
      Sensor Networks.
AB  - This paper proposes an agricultural environment monitoring server system for
      monitoring information concerning an outdoors agricultural production environment
      utilizing Wireless Sensor Network (WSN) technology. The proposed agricultural
      environment monitoring server system collects environmental and soil information
      on the outdoors through WSN-based environmental and soil sensors, collects image
      information through CCTVs, and collects location information using GPS modules.
      This collected information is converted into a database through the agricultural
      environment monitoring server consisting of a sensor manager, which manages
      information collected from the WSN sensors, an image information manager, which
      manages image information collected from CCTVs, and a GPS manager, which
      processes location information of the agricultural environment monitoring server
      system, and provides it to producers. In addition, a solar cell-based power
      supply is implemented for the server system so that it could be used in
      agricultural environments with insufficient power infrastructure. This
      agricultural environment monitoring server system could even monitor the
      environmental information on the outdoors remotely, and it could be expected that
      the use of such a system could contribute to increasing crop yields and improving
      quality in the agricultural field by supporting the decision making of crop
      producers through analysis of the collected information.

PMID- 22163521
TI  - Design of a pressure sensor based on optical fiber Bragg grating lateral
      deformation.
AB  - This paper describes steps involved in the design and realization of a new type
      of pressure sensor based on the optical fiber Bragg grating. A traditional
      pressure sensor has very limited usage in heavy industrial environments,
      particularly in explosive or electromagnetically noisy environments. Utilization
      of optics in these environments eliminates all surrounding influences. An initial
      motivation for our development was the research, experimental validation, and
      realization of a complex smart pressure sensor based on the optical principle.
      The main benefit of this solution consists of increasing sensitivity, resistance
      to electromagnetic interference, dimensions, and potential increased accuracy.

PMID- 22163522
TI  - Sensor architecture and task classification for agricultural vehicles and
      environments.
AB  - The long time wish of endowing agricultural vehicles with an increasing degree of
      autonomy is becoming a reality thanks to two crucial facts: the broad diffusion
      of global positioning satellite systems and the inexorable progress of computers
      and electronics. Agricultural vehicles are currently the only self-propelled
      ground machines commonly integrating commercial automatic navigation systems.
      Farm equipment manufacturers and satellite-based navigation system providers, in
      a joint effort, have pushed this technology to unprecedented heights; yet there
      are many unresolved issues and an unlimited potential still to uncover. The
      complexity inherent to intelligent vehicles is rooted in the selection and
      coordination of the optimum sensors, the computer reasoning techniques to process
      the acquired data, and the resulting control strategies for automatic actuators.
      The advantageous design of the network of onboard sensors is necessary for the
      future deployment of advanced agricultural vehicles. This article analyzes a
      variety of typical environments and situations encountered in agricultural
      fields, and proposes a sensor architecture especially adapted to cope with them.
      The strategy proposed groups sensors into four specific subsystems: global
      localization, feedback control and vehicle pose, non-visual monitoring, and local
      perception. The designed architecture responds to vital vehicle tasks classified
      within three layers devoted to safety, operative information, and automatic
      actuation. The success of this architecture, implemented and tested in various
      agricultural vehicles over the last decade, rests on its capacity to integrate
      redundancy and incorporate new technologies in a practical way.

PMID- 22163523
TI  - Ultrasonic sensitivity of strain-insensitive fiber Bragg grating sensors and
      evaluation of ultrasound-induced strain.
AB  - In conventional ultrasound detection in structures, a fiber Bragg grating (FBG)
      is glued on or embedded in the structure. However, application of strain to the
      structure can influence the sensitivity of the FBG toward ultrasound and can
      prevent its effective detection. An FBG can work as a strain-insensitive
      ultrasound sensor when it is not directly glued to the monitored structure, but
      is instead applied to a small thin plate to form a mobile sensor. Another
      possible configuration is to affix an FBG-inscribed optical fiber without the
      grating section attached to the monitored structure. In the present study,
      sensitivity to ultrasound propagated through an aluminum plate was compared for a
      strain-insensitive FBG sensor and an FBG sensor installed in a conventional
      manner. Strains induced by ultrasound from a piezoelectric transducer and by
      quasi-acoustic emission of a pencil lead break were also quantitatively evaluated
      from the response amplitude of the FBG sensor. Experimental results showed that
      the reduction in the signal-to-noise ratio for ultrasound detection with strain
      insensitive FBG sensors, relative to traditionally-installed FBG sensors, was
      only 6 dB, and the ultrasound-induced strain varied within a range of sub-micron
      strains.

PMID- 22163524
TI  - Approximate nearest neighbor search by residual vector quantization.
AB  - A recently proposed product quantization method is efficient for large scale
      approximate nearest neighbor search, however, its performance on unstructured
      vectors is limited. This paper introduces residual vector quantization based
      approaches that are appropriate for unstructured vectors. Database vectors are
      quantized by residual vector quantizer. The reproductions are represented by
      short codes composed of their quantization indices. Euclidean distance between
      query vector and database vector is approximated by asymmetric distance, i.e.,
      the distance between the query vector and the reproduction of the database
      vector. An efficient exhaustive search approach is proposed by fast computing the
      asymmetric distance. A straight forward non-exhaustive search approach is
      proposed for large scale search. Our approaches are compared to two state-of-the
      art methods, spectral hashing and product quantization, on both structured and
      unstructured datasets. Results show that our approaches obtain the best results
      in terms of the trade-off between search quality and memory usage.

PMID- 22163525
TI  - A high-throughput enzyme assay for organophosphate residues in milk.
AB  - A rapid, high-sensitivity, chemiluminescence (CL) enzyme assay for the
      determination of organophosphate (OP) residues in milk is presented. The assay
      for quantification of OP residues in milk is based on the inhibition of enzyme
      butyrylcholinesterase (BuChE). BuChE was stabilized and preloaded in 384 well
      plates at 30  degrees C. The assay permits rapid determination of OPs in milk
      within 12 min including an incubation step. The enzyme assay was tested for
      individual and mixtures of OPs such as methyl paraoxon (MPOx), methyl parathion
      (MP) and malathion (MT) in milk to evaluate their synergistic effect on BuChE
      inhibition. Good linearity was obtained in the range 0.005-50 MUg.L(-1) for MPOx
      and 0.5-1,000 MUg.L(-1) for MP as well as MT in milk. Mean recovery of 93.2%
      98.6% was obtained for MPOx spiked milk samples with 0.99%-1.67% reproducibility
      (RSD). The proposed method facilitated rapid screening of milk samples in 384
      well plate formats with further miniaturization presented in 1,536 well plates.

PMID- 22163526
TI  - Ca2+-regulated photoproteins: effective immunoassay reporters.
AB  - Ca2+-regulated photoproteins of luminous marine coelenterates are of interest and
      a challenge for researchers as a unique bioluminescent system and as a promising
      analytical instrument for both in vivo and in vitro applications. The proteins
      are comprehensively studied as to biochemical properties, tertiary structures,
      bioluminescence mechanism, etc. This knowledge, along with available recombinant
      proteins serves the basis for development of unique bioluminescent detection
      systems that are "self-contained", triggerable, fast, highly sensitive, and non
      hazardous. In the paper, we focus on the use of photoproteins as reporters in
      binding assays based on immunological recognition element--bioluminescent
      immunoassay and hybridization immunoassay, their advantages and prospects.

PMID- 22163527
TI  - Pressure sensing in high-refractive-index liquids using long-period gratings
      nanocoated with silicon nitride.
AB  - The paper presents a novel pressure sensor based on a silicon nitride (SiNx)
      nanocoated long-period grating (LPG). The high-temperature, radio-frequency
      plasma-enhanced chemical-vapor-deposited (RF PECVD) SiNx nanocoating was applied
      to tune the sensitivity of the LPG to the external refractive index. The
      technique allows for deposition of good quality, hard and wear-resistant
      nanofilms as required for optical sensors. Thanks to the SiNx nanocoating it is
      possible to overcome a limitation of working in the external-refractive-index
      range, which for a bare fiber cannot be close to that of the cladding. The
      nanocoated LPG-based sensing structure we developed is functional in high
      refractive-index liquids (nD>1.46) such as oil or gasoline, with pressure
      sensitivity as high as when water is used as a working liquid. The nanocoating
      developed for this experiment not only has the highest refractive index ever
      achieved in LPGs (n>2.2 at lambda=1,550 nm), but is also the thinnest (<100 nm)
      able to tune the external-refractive-index sensitivity of the gratings. To the
      best of our knowledge, this is the first time a nanocoating has been applied on
      LPGs that is able to simultaneously tune the refractive-index sensitivity and to
      enable measurements of other parameters.

PMID- 22163528
TI  - A ferrocene-quinoxaline derivative as a highly selective probe for colorimetric
      and redox sensing of toxic mercury(II) cations.
AB  - A new chemosensor molecule 3 based on a ferrocene-quinoxaline dyad recognizes
      mercury (II) cations in acetonitrile solution. Upon recognition, an anodic shift
      of the ferrocene/ferrocenium oxidation peaks and a progressive red-shift
      (Deltalambda=140 nm) of the low-energy band, are observed in its absorption
      spectrum. This change in the absorption spectrum is accompanied by a colour
      change from orange to deep green, which can be used for a "naked-eye" detection
      of this metal cation.

PMID- 22163529
TI  - Bioinspired electronic white cane implementation based on a LIDAR, a tri-axial
      accelerometer and a tactile belt.
AB  - This work proposes the creation of a bioinspired electronic white cane for blind
      people using the whiskers principle for short-range navigation and exploration.
      Whiskers are coarse hairs of an animal's face that tells the animal that it has
      touched something using the nerves of the skin. In this work the raw data
      acquired from a low-size terrestrial LIDAR and a tri-axial accelerometer is
      converted into tactile information using several electromagnetic devices
      configured as a tactile belt. The LIDAR and the accelerometer are attached to the
      user's forearm and connected with a wire to the control unit placed on the belt.
      Early validation experiments carried out in the laboratory are promising in terms
      of usability and description of the environment.

PMID- 22163530
TI  - Determination of silver(I) by differential pulse voltammetry using a glassy
      carbon electrode modified with synthesized N-(2-aminoethyl)-4,4'-bipyridine.
AB  - A new modified glassy carbon electrode (GCE) based on a synthesized N-(2
      aminoethyl)-4,4'-bipyridine (ABP) was developed for the determination of Ag(I) by
      differential pulse voltammetry (DPV). ABP was covalently immobilized on GC
      electrodes surface using 4-nitrobenzendiazonium (4-NBD) and glutaraldehyde (GA).
      The Ag(I) ions were preconcentrated by chemical interaction with bipyridine under
      a negative potential (-0.6 V); then the reduced ions were oxidized by
      differential pulse voltammetry and a peak was observed at 0.34 V. The calibration
      curve was linear in the concentration range from 0.05 MUM to 1 MUM Ag(I) with a
      detection limit of 0.025 MUM and RSD=3.6%, for 0.4 MUM Ag(I). The presence of
      several common ions in more than 125-fold excess had no effect on the
      determination of Ag(I). The developed sensor was applied to the determination of
      Ag(I) in water samples using a standard addition method.

PMID- 22163531
TI  - Sensing-applications of surface-based single vesicle arrays.
AB  - A single lipid vesicle can be regarded as an autonomous ultra-miniaturised 3D
      biomimetic "scaffold" (O>=13 nm) ideally suited for reconstitution and
      interrogation of biochemical processes. The enclosing lipid bilayer membrane of a
      vesicle can be applied for studying binding (protein/lipid or receptor/ligand
      interactions) or transmembrane events (membrane permeability or ion channel
      activation) while the aqueous vesicle lumen can be used for confining few or
      single macromolecules and probe, e.g., protein folding, catalytic pathways of
      enzymes or more complex biochemical reactions, such as signal transduction
      cascades. Immobilisation (arraying) of single vesicles on a solid support is an
      extremely useful technique that allows detailed characterisation of vesicle
      preparations using surface sensitive techniques, in particular fluorescence
      microscopy. Surface-based single vesicle arrays allow a plethora of prototypic
      sensing applications in a high throughput format with high spatial and high
      temporal resolution. In this review we present a series of applications of single
      vesicle arrays for screening/sensing of: membrane curvature dependent protein
      lipid interactions, bilayer tension, reactions triggered in the vesicle lumen,
      the activity of transmembrane protein channels and biological membrane fusion
      reactions.

PMID- 22163532
TI  - Reliable location-based services from radio navigation systems.
AB  - Loran is a radio-based navigation system originally designed for naval
      applications. We show that Loran-C's high-power and high repeatable accuracy are
      fantastic for security applications. First, we show how to derive a precise
      location tag--with a sensitivity of about 20 meters--that is difficult to project
      to an exact location. A device can use our location tag to block or allow certain
      actions, without knowing its precise location. To ensure that our tag is
      reproducible we make use of fuzzy extractors, a mechanism originally designed for
      biometric authentication. We build a fuzzy extractor specifically designed for
      radio-type errors and give experimental evidence to show its effectiveness.
      Second, we show that our location tag is difficult to predict from a distance.
      For example, an observer cannot predict the location tag inside a guarded data
      center from a few hundreds of meters away. As an application, consider a location
      aware disk drive that will only work inside the data center. An attacker who
      steals the device and is capable of spoofing Loran-C signals, still cannot make
      the device work since he does not know what location tag to spoof. We provide
      experimental data supporting our unpredictability claim.

PMID- 22163533
TI  - Resolution enhancement in surface plasmon resonance sensor based on waveguide
      coupled mode by combining a bimetallic approach.
AB  - In this study, we present and demonstrate a new route to a great enhancement in
      resolution of surface plasmon resonance sensors. Basically, our approach combines
      a waveguide coupled plasmonic mode and a kind of Au/Ag bimetallic enhancement
      concept. Theoretical modeling was carried out by solving Fresnel equations for
      the multilayer stack of prism/Ag inner-metal layer/dielectric waveguide/Au outer
      metal layer. The inner Ag layer couples incident light to a guided wave and makes
      more fields effectively concentrated on the outer Au surface. A substantial
      enhancement in resolution was experimentally verified for the model stack using a
      ZnS-SiO2 waveguide layer.

PMID- 22163534
TI  - An efficient management system for wireless sensor networks.
AB  - Wireless sensor networks have garnered considerable attention recently. Networks
      typically have many sensor nodes, and are used in commercial, medical,
      scientific, and military applications for sensing and monitoring the physical
      world. Many researchers have attempted to improve wireless sensor network
      management efficiency. A Simple Network Management Protocol (SNMP)-based sensor
      network management system was developed that is a convenient and effective way
      for managers to monitor and control sensor network operations. This paper
      proposes a novel WSNManagement system that can show the connections stated of
      relationships among sensor nodes and can be used for monitoring, collecting, and
      analyzing information obtained by wireless sensor networks. The proposed network
      management system uses collected information for system configuration. The
      function of performance analysis facilitates convenient management of sensors.
      Experimental results show that the proposed method enhances the alive rate of an
      overall sensor node system, reduces the packet lost rate by roughly 5%, and
      reduces delay time by roughly 0.2 seconds. Performance analysis demonstrates that
      the proposed system is effective for wireless sensor network management.

PMID- 22163535
TI  - Direct detection of the biological toxin in acidic environment by electrochemical
      impedimetric immunosensor.
AB  - This study describes the direct detection of the biological toxin (Ricin) in
      acidic environment without pH adjustment by hydrophobically modified
      electrochemical impedance immunosensor (EII). The nano-porous aluminum substrate
      for EII was hydrophobically modified via self-assembled monolayer (SAM) of APTES.
      Biosensor for the detection of the Ricin was fabricated by the covalent cross
      linking of antibody (Ab) with APTES-SAM. The immunoreactions between the
      immobilized Ab and the biological toxin in several diagnostic solutions were
      monitored by the electrochemical impedance spectroscopy (EIS) under the
      polarization of EII versus reference electrode. EII could detect the presence of
      the biological toxin in acidic foods in 20 mins without pH adjustment. The
      negatively charged ions including hydroxides would be adsorbed on the hydrophobic
      body of APTES-SAMs by the polarization during EIS analysis, and offset the effect
      of acids on the immunological activity of the immobilized Ab. It suggested that
      the adsorption of negatively charged ions helped to keep the immunological
      activities of the immobilized Ab on EII in acidic environment. Proposed mechanism
      of the localized pH adjustment that makes possible immunoreaction occurrence in
      low pH sample matrix is briefly discussed.

PMID- 22163536
TI  - Myocardial motion analysis for determination of Tei-index of human heart.
AB  - The Tei index, an important indicator of heart function, lacks a direct method to
      compute because it is difficult to directly evaluate the isovolumic contraction
      time (ICT) and isovolumic relaxation time (IRT) from which the Tei index can be
      obtained. In this paper, based on the proposed method of accurately measuring the
      cardiac cycle physical phase, a direct method of calculating the Tei index is
      presented. The experiments based on real heart medical images show the
      effectiveness of this method. Moreover, a new method of calculating left
      ventricular wall motion amplitude is proposed and the experiments show its
      satisfactory performance.

PMID- 22163537
TI  - Pervasive monitoring--an intelligent sensor pod approach for standardised
      measurement infrastructures.
AB  - Geo-sensor networks have traditionally been built up in closed monolithic
      systems, thus limiting trans-domain usage of real-time measurements. This paper
      presents the technical infrastructure of a standardised embedded sensing device,
      which has been developed in the course of the Live Geography approach. The sensor
      pod implements data provision standards of the Sensor Web Enablement initiative,
      including an event-based alerting mechanism and location-aware Complex Event
      Processing functionality for detection of threshold transgression and quality
      assurance. The goal of this research is that the resultant highly flexible
      sensing architecture will bring sensor network applications one step further
      towards the realisation of the vision of a "digital skin for planet earth". The
      developed infrastructure can potentially have far-reaching impacts on sensor
      based monitoring systems through the deployment of ubiquitous and fine-grained
      sensor networks. This in turn allows for the straight-forward use of live sensor
      data in existing spatial decision support systems to enable better-informed
      decision-making.

PMID- 22163538
TI  - Map building and monte carlo localization using global appearance of
      omnidirectional images.
AB  - In this paper we deal with the problem of map building and localization of a
      mobile robot in an environment using the information provided by an
      omnidirectional vision sensor that is mounted on the robot. Our main objective
      consists of studying the feasibility of the techniques based in the global
      appearance of a set of omnidirectional images captured by this vision sensor to
      solve this problem. First, we study how to describe globally the visual
      information so that it represents correctly locations and the geometrical
      relationships between these locations. Then, we integrate this information using
      an approach based on a spring-mass-damper model, to create a topological map of
      the environment. Once the map is built, we propose the use of a Monte Carlo
      localization approach to estimate the most probable pose of the vision system and
      its trajectory within the map. We perform a comparison in terms of computational
      cost and error in localization. The experimental results we present have been
      obtained with real indoor omnidirectional images.

PMID- 22163539
TI  - A combined experimental and theoretical study on the immunoassay of human
      immunoglobulin using a quartz crystal microbalance.
AB  - We investigate a immunoassay biosensor that employs a Quartz Crystal Microbalance
      (QCM) to detect the specific binding reaction of the (Human IgG1)-(Anti-Human
      IgG1) protein pair under physiological conditions. In addition to experiments, a
      three dimensional time domain finite element method (FEM) was used to perform
      simulations for the biomolecular binding reaction in microfluidic channels. In
      particular, we discuss the unsteady convective diffusion in the transportation
      tube, which conveys the buffer solution containing the analyte molecules into the
      micro-channel where the QCM sensor lies. It is found that the distribution of the
      analyte concentration in the tube is strongly affected by the flow field,
      yielding large discrepancies between the simulations and experimental results.
      Our analysis shows that the conventional assumption of the analyte concentration
      in the inlet of the micro-channel being uniform and constant in time is
      inadequate. In addition, we also show that the commonly used procedure in kinetic
      analysis for estimating binding rate constants from the experimental data would
      underestimate these rate constants due to neglected diffusion processes from the
      inlet to the reaction surface. A calibration procedure is proposed to supplement
      the basic kinetic analysis, thus yielding better consistency with experiments.

PMID- 22163540
TI  - Characterization of buoyant fluorescent particles for field observations of water
      flows.
AB  - In this paper, the feasibility of off-the-shelf buoyant fluorescent microspheres
      as particle tracers in turbid water flows is investigated. Microspheres'
      fluorescence intensity is experimentally measured and detected in placid aqueous
      suspensions of increasing concentrations of clay to simulate typical conditions
      occurring in natural drainage networks. Experiments are conducted in a broad
      range of clay concentrations and particle immersion depths by using
      photoconductive cells and image-based sensing technologies. Results obtained with
      both methodologies exhibit comparable trends and show that the considered
      particles are fairly detectable in critically turbid water flows. Further
      information on performance and integration of the studied microspheres in low
      cost measurement instrumentation for field observations is obtained through
      experiments conducted in a custom built miniature water channel. This
      experimental characterization provides a first assessment of the feasibility of
      commercially available buoyant fluorescent beads in the analysis of high
      turbidity surface water flows. The proposed technology may serve as a minimally
      invasive sensing system for hazardous events, such as pollutant diffusion in
      natural streams and flash flooding due to extreme rainfall.

PMID- 22163541
TI  - Nitrite biosensing via selective enzymes--a long but promising route.
AB  - The last decades have witnessed a steady increase of the social and political
      awareness for the need of monitoring and controlling environmental and industrial
      processes. In the case of nitrite ion, due to its potential toxicity for human
      health, the European Union has recently implemented a number of rules to restrict
      its level in drinking waters and food products. Although several analytical
      protocols have been proposed for nitrite quantification, none of them enable a
      reliable and quick analysis of complex samples. An alternative approach relies on
      the construction of biosensing devices using stable enzymes, with both high
      activity and specificity for nitrite. In this paper we review the current state
      of-the-art in the field of electrochemical and optical biosensors using nitrite
      reducing enzymes as biorecognition elements and discuss the opportunities and
      challenges in this emerging market.

PMID- 22163542
TI  - The use of wearable inertial motion sensors in human lower limb biomechanics
      studies: a systematic review.
AB  - Wearable motion sensors consisting of accelerometers, gyroscopes and magnetic
      sensors are readily available nowadays. The small size and low production costs
      of motion sensors make them a very good tool for human motions analysis. However,
      data processing and accuracy of the collected data are important issues for
      research purposes. In this paper, we aim to review the literature related to
      usage of inertial sensors in human lower limb biomechanics studies. A systematic
      search was done in the following search engines: ISI Web of Knowledge, Medline,
      SportDiscus and IEEE Xplore. Thirty nine full papers and conference abstracts
      with related topics were included in this review. The type of sensor involved,
      data collection methods, study design, validation methods and its applications
      were reviewed.

PMID- 22163543
TI  - A wireless sensor network-based ubiquitous paprika growth management system.
AB  - Wireless Sensor Network (WSN) technology can facilitate advances in productivity,
      safety and human quality of life through its applications in various industries.
      In particular, the application of WSN technology to the agricultural area, which
      is labor-intensive compared to other industries, and in addition is typically
      lacking in IT technology applications, adds value and can increase the
      agricultural productivity. This study attempts to establish a ubiquitous
      agricultural environment and improve the productivity of farms that grow paprika
      by suggesting a 'Ubiquitous Paprika Greenhouse Management System' using WSN
      technology. The proposed system can collect and monitor information related to
      the growth environment of crops outside and inside paprika greenhouses by
      installing WSN sensors and monitoring images captured by CCTV cameras. In
      addition, the system provides a paprika greenhouse environment control facility
      for manual and automatic control from a distance, improves the convenience and
      productivity of users, and facilitates an optimized environment to grow paprika
      based on the growth environment data acquired by operating the system.

PMID- 22163544
TI  - Large scale application of vibration sensors for fan monitoring at commercial
      layer hen houses.
AB  - Continuously monitoring the operation of each individual fan can significantly
      improve the measurement quality of aerial pollutant emissions from animal
      buildings that have a large number of fans. To monitor the fan operation by
      detecting the fan vibration is a relatively new technique. A low-cost electronic
      vibration sensor was developed and commercialized. However, its large scale
      application has not yet been evaluated. This paper presents long-term performance
      results of this vibration sensor at two large commercial layer houses. Vibration
      sensors were installed on 164 fans of 130 cm diameter to continuously monitor the
      fan on/off status for two years. The performance of the vibration sensors was
      compared with fan rotational speed (FRS) sensors. The vibration sensors exhibited
      quick response and high sensitivity to fan operations and therefore satisfied the
      general requirements of air quality research. The study proved that detecting fan
      vibration was an effective method to monitor the on/off status of a large number
      of single-speed fans. The vibration sensor itself was $2 more expensive than a
      magnetic proximity FRS sensor but the overall cost including installation and
      data acquisition hardware was $77 less expensive than the FRS sensor. A total of
      nine vibration sensors failed during the study and the failure rate was related
      to the batches of product. A few sensors also exhibited unsteady sensitivity. As
      a new product, the quality of the sensor should be improved to make it more
      reliable and acceptable.

PMID- 22163545
TI  - Use of multi-functional flexible micro-sensors for in situ measurement of
      temperature, voltage and fuel flow in a proton exchange membrane fuel cell.
AB  - Temperature, voltage and fuel flow distribution all contribute considerably to
      fuel cell performance. Conventional methods cannot accurately determine parameter
      changes inside a fuel cell. This investigation developed flexible and multi
      functional micro sensors on a 40 MUm-thick stainless steel foil substrate by
      using micro-electro-mechanical systems (MEMS) and embedded them in a proton
      exchange membrane fuel cell (PEMFC) to measure the temperature, voltage and flow.
      Users can monitor and control in situ the temperature, voltage and fuel flow
      distribution in the cell. Thereby, both fuel cell performance and lifetime can be
      increased.

PMID- 22163546
TI  - Performance bound for extended target tracking using high resolution sensors.
AB  - This article concerns the problem of the estimation bound for tracking an
      extended target observed by a high resolution sensor. Two types of commonly used
      models for extended targets and the corresponding posterior Cramer-Rao lower
      bound (PCRLB) are discussed. The first type is the equation-extension model which
      extends the state space to include parameters such as target size and shape.
      Thus, the extended state vector can be estimated through the measurements
      obtained by a high resolution sensor. The measurement vector is also an expansion
      of the conventional one, and the additional measurements such as target extent
      can provide extra information for the estimation. The second model is based on
      multiple target measurements, each of which is an independent random draw from a
      spatial probability distribution. As the number of measurements per frame is
      unknown and random, the general form of the measurement contribution to the
      Fisher information matrix (FIM) conditional on the number of measurements is
      presented, and an extended information reduction factor (EIRF) approach is
      proposed to calculate the overall FIM and, therefore, the PCRLB. The bound of the
      second extended target model is also less than that of the point model, on
      condition that the average number of measurements is greater than one.
      Illustrative simulation examples of the two models are discussed and
      demonstrated.

PMID- 22163547
TI  - Detection of cartilage oligomeric matrix protein using a quartz crystal
      microbalance.
AB  - Current methods for diagnosing early stage osteoarthritis (OA) based on the
      magnetic resonance imaging and enzyme-linked immunosorbent assay methods are
      specific, but require specialized laboratory facilities and highly trained
      personal to obtain a definitive result. In this work, a user friendly and non
      invasive quartz crystal microbalance (QCM) immunosensor method has been developed
      to detect Cartilage Oligomeric Matrix Protein (COMP) for early stage OA
      diagnosis. This QCM immunosensor was fabricated to immobilize COMP antibodies
      utilizing the self-assembled monolayer technique. The surface properties of the
      immunosensor were characterized by its FTIR and electrochemical impedance spectra
      (EIS). The feasibility study was based on urine samples obtained from 41
      volunteers. Experiments were carried out in a flow system and the reproducibility
      of the electrodes was evaluated by the impedance measured by EIS. Its potential
      dynamically monitored the immunoreaction processes and could increase the
      efficiency and sensitivity of COMP detection in laboratory-cultured preparations
      and clinical samples. The frequency responses of the QCM immunosensor changed
      from 6 kHz when testing 50 ng/mL COMP concentration. The linear regression
      equation of frequency shift and COMP concentration was determined as: y=0.0872
      x+1.2138 (R2=0.9957). The COMP in urine was also determined by both QCM and EIS
      for comparison. A highly sensitive, user friendly and cost effective analytical
      method for the early stage OA diagnosis has thus been successfully developed.

PMID- 22163548
TI  - Sub-frequency interval approach in electromechanical impedance technique for
      concrete structure health monitoring.
AB  - The electromechanical (EM) impedance technique using piezoelectric lead zirconate
      titanate (PZT) transducers for structural health monitoring (SHM) has attracted
      considerable attention in various engineering fields. In the conventional EM
      impedance technique, the EM admittance of a PZT transducer is used as a damage
      indicator. Statistical analysis methods such as root mean square deviation (RMSD)
      have been employed to associate the damage level with the changes in the EM
      admittance signatures, but it is difficult to determine the location of damage
      using such methods. This paper proposes a new approach by dividing the large
      frequency (30-400 kHz) range into sub-frequency intervals and calculating their
      respective RMSD values. The RMSD of the sub-frequency intervals (RMSD-S) will be
      used to study the severity and location of damage. An experiment is carried out
      on a real size concrete structure subjected to artificial damage. It is observed
      that damage close to the PZT changes the high frequency range RMSD-S
      significantly, while the damage far away from the PZT changes the RMSD-S in the
      low frequency range significantly. The relationship between the frequency range
      and the PZT sensing region is also presented. Finally, a damage identification
      scheme is proposed to estimate the location and severity of damage in concrete
      structures.

PMID- 22163549
TI  - Study on additional carrier sensing for IEEE 802.15.4 wireless sensor networks.
AB  - Wireless sensor networks based on the IEEE 802.15.4 standard are able to achieve
      low-power transmissions in the guise of low-rate and short-distance wireless
      personal area networks (WPANs). The slotted carrier sense multiple access with
      collision avoidance (CSMA/CA) is used for contention mechanism. Sensor nodes
      perform a backoff process as soon as the clear channel assessment (CCA) detects a
      busy channel. In doing so they may neglect the implicit information of the failed
      CCA detection and further cause the redundant sensing. The blind backoff process
      in the slotted CSMA/CA will cause lower channel utilization. This paper proposes
      an additional carrier sensing (ACS) algorithm based on IEEE 802.15.4 to enhance
      the carrier sensing mechanism for the original slotted CSMA/CA. An analytical
      Markov chain model is developed to evaluate the performance of the ACS algorithm.
      Both analytical and simulation results show that the proposed algorithm performs
      better than IEEE 802.15.4, which in turn significantly improves throughput,
      average medium access control (MAC) delay and power consumption of CCA detection.

PMID- 22163550
TI  - A bacterial biosensor for oxidative stress using the constitutively expressed
      redox-sensitive protein roGFP2.
AB  - A highly specific, high throughput-amenable bacterial biosensor for chemically
      induced cellular oxidation was developed using constitutively expressed redox
      sensitive green fluorescent protein roGFP2 in E. coli (E. coli-roGFP2). Disulfide
      formation between two key cysteine residues of roGFP2 was assessed using a double
      wavelength ratiometric approach. This study demonstrates that only a few minutes
      were required to detect oxidation using E. coli-roGFP2, in contrast to
      conventional bacterial oxidative stress sensors. Cellular oxidation induced by
      hydrogen peroxide, menadione, sodium selenite, zinc pyrithione, triphenyltin and
      naphthalene became detectable after 10 seconds and reached the maxima between 80
      to 210 seconds, contrary to Cd(2+), Cu(2+), Pb(2+), Zn(2+) and sodium arsenite,
      which induced the oxidation maximum immediately. The lowest observable effect
      concentrations (in ppm) were determined as 1.0 * 10(-7) (arsenite), 1.0 * 10(-4)
      (naphthalene), 1.0 * 10(-4) (Cu(2+)), 3.8 * 10(-4) (H(2)O(2)), 1.0 * 10(-3)
      (Cd(2+)), 1.0 * 10(-3) (Zn(2+)), 1.0 * 10(-2) (menadione), 1.0 (triphenyltin),
      1.56 (zinc pyrithione), 3.1 (selenite) and 6.3 (Pb(2+)), respectively. Heavy
      metal-induced oxidation showed unclear response patterns, whereas concentration
      dependent sigmoid curves were observed for other compounds. In vivo GSH content
      and in vitro roGFP2 oxidation assays together with E. coli-roGFP2 results suggest
      that roGFP2 is sensitive to redox potential change and thiol modification induced
      by environmental stressors. Based on redox-sensitive technology, E. coli-roGFP2
      provides a fast comprehensive detection system for toxicants that induce cellular
      oxidation.

PMID- 22163551
TI  - EMMNet: sensor networking for electricity meter monitoring.
AB  - Smart sensors are emerging as a promising technology for a large number of
      application domains. This paper presents a collection of requirements and
      guidelines that serve as a basis for a general smart sensor architecture to
      monitor electricity meters. It also presents an electricity meter monitoring
      network, named EMMNet, comprised of data collectors, data concentrators, hand
      held devices, a centralized server, and clients. EMMNet provides long-distance
      communication capabilities, which make it suitable suitable for complex urban
      environments. In addition, the operational cost of EMMNet is low, compared with
      other existing remote meter monitoring systems based on GPRS. A new dynamic tree
      protocol based on the application requirements which can significantly improve
      the reliability of the network is also proposed. We are currently conducting
      tests on five networks and investigating network problems for further
      improvements. Evaluation results indicate that EMMNet enhances the efficiency and
      accuracy in the reading, recording, and calibration of electricity meters.

PMID- 22163552
TI  - Implementation of a vector-based tracking loop receiver in a pseudolite
      navigation system.
AB  - We propose a vector tracking loop (VTL) algorithm for an asynchronous pseudolite
      navigation system. It was implemented in a software receiver and experiments in
      an indoor navigation system were conducted. Test results show that the VTL
      successfully tracks signals against the near-far problem, one of the major
      limitations in pseudolite navigation systems, and could improve positioning
      availability by extending pseudolite navigation coverage.

PMID- 22163553
TI  - Effects of electric potential treatment of a chromium hexacyanoferrate modified
      biosensor based on PQQ-dependent glucose dehydrogenase.
AB  - A novel potential treatment technique applied to a glucose biosensor that is
      based on pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase (GDH) and
      chromium hexacyanoferrate (CrHCF) incorporated into a platinum (Pt) electrode was
      demonstrated. CrHCF, serving as a mediator, was electrochemically deposited on
      the Pt electrode as ascertained by CV, SEM, FTIR and XPS measurements. The
      potential treatment of CrHCF, which converts Fe(II) to Fe(III), enables the
      glucose detection. The amperometric measurement linearity of the biosensor was up
      to 20 mM (R = 0.9923), and the detection sensitivity was 199.94 nA/mM per cm(2).
      More importantly, this biosensor remained stable for >270 days.

PMID- 22163554
TI  - QCM-arrays for sensing terpenes in fresh and dried herbs via bio-mimetic MIP
      layers.
AB  - A piezoelectric 10 MHz multichannel quartz crystal microbalance (MQCM), coated
      with six molecularly imprinted polystyrene artificial recognition membranes have
      been developed for selective quantification of terpenes emanated from fresh and
      dried Lamiaceae family species, i.e., rosemary (Rosmarinus Officinalis L.), basil
      (Ocimum Basilicum) and sage (Salvia Officinalis). Optimal e-nose parameters, such
      as layer heights (1-6 KHz), sensitivity <20 ppm of analytes, selectivity at 50
      ppm of terpenes, repeatability and reproducibility were thoroughly adjusted prior
      to online monitoring. Linearity in reversible responses over a wide concentration
      range <20-250 ppm has been achieved. Discrimination between molecules of similar
      molar masses, even for isomers, e.g. alpha-pinene and beta-pinene is possible.
      The array has proven its sensitive and selective properties of sensor responses
      (20-1,200 Hz) for the difference of fresh and dried herbs. The sensor data
      attained was validated by GC-MS, to analyze the profiles of sensor emanation
      patterns. The shelf-life of herbs was monitored via emanation of organic
      volatiles during a few days. Such an array in association with data analysis
      tools can be utilized for characterizing complex mixtures.

PMID- 22163555
TI  - A high sensitivity micro format chemiluminescence enzyme inhibition assay for
      determination of Hg(II).
AB  - A highly sensitive and specific enzyme inhibition assay based on alcohol oxidase
      (AlOx) and horseradish peroxidase (HRP) for determination of mercury Hg(II) in
      water samples has been presented. This article describes the optimization and
      miniaturization of an enzymatic assay using a chemiluminescence reaction. The
      analytical performance and detection limit for determination of Hg(II) was
      optimized in 96 well plates and further extended to 384 well plates with a 10
      fold reduction in assay volume. Inhibition of the enzyme activity by dissolved
      Hg(II) was found to be linear in the range 5-500 pg.mL(-1) with 3% CV in inter
      batch assay. Due to miniaturization of assay in 384 well plates, Hg(II) was
      measurable as low as 1 pg.mL(-1) within 15 min. About 10-fold more specificity of
      the developed assay for Hg(II) analysis was confirmed by challenging with
      interfering divalent metal ions such as cadmium Cd(II) and lead Pb(II). Using the
      proposed assay we could successfully demonstrate that in a composite mixture of
      Hg(II), Cd(II) and Pb(II), inhibition by each metal ion is significantly enhanced
      in the presence of the others. Applicability of the proposed assay for the
      determination of the Hg(II) in spiked drinking and sea water resulted in
      recoveries ranging from 100-110.52%.

PMID- 22163556
TI  - In-situ monitoring of internal local temperature and voltage of proton exchange
      membrane fuel cells.
AB  - The distribution of temperature and voltage of a fuel cell are key factors that
      influence performance. Conventional sensors are normally large, and are also
      useful only for making external measurements of fuel cells. Centimeter-scale
      sensors for making invasive measurements are frequently unable to accurately
      measure the interior changes of a fuel cell. This work focuses mainly on
      fabricating flexible multi-functional microsensors (for temperature and voltage)
      to measure variations in the local temperature and voltage of proton exchange
      membrane fuel cells (PEMFC) that are based on micro-electro-mechanical systems
      (MEMS). The power density at 0.5 V without a sensor is 450 mW/cm(2), and that
      with a sensor is 426 mW/cm(2). Since the reaction area of a fuel cell with a
      sensor is approximately 12% smaller than that without a sensor, but the
      performance of the former is only 5% worse.

PMID- 22163557
TI  - Optimization of the sampling periods and the quantization bit lengths for
      networked estimation.
AB  - This paper is concerned with networked estimation, where sensor data are
      transmitted over a network of limited transmission rate. The transmission rate
      depends on the sampling periods and the quantization bit lengths. To investigate
      how the sampling periods and the quantization bit lengths affect the estimation
      performance, an equation to compute the estimation performance is provided. An
      algorithm is proposed to find sampling periods and quantization bit lengths
      combination, which gives good estimation performance while satisfying the
      transmission rate constraint. Through the numerical example, the proposed
      algorithm is verified.

PMID- 22163558
TI  - Aerosol optical retrieval and surface reflectance from airborne remote sensing
      data over land.
AB  - Quantitative analysis of atmospheric optical properties and surface reflectance
      can be performed by applying radiative transfer theory in the Atmosphere-Earth
      coupled system, for the atmospheric correction of hyperspectral remote sensing
      data. This paper describes a new physically-based algorithm to retrieve the
      aerosol optical thickness at 550 nm (tau(550)) and the surface reflectance (rho)
      from airborne acquired data in the atmospheric window of the Visible and Near
      Infrared (VNIR) range. The algorithm is realized in two modules. Module A
      retrieves tau(550) with a minimization algorithm, then Module B retrieves the
      surface reflectance rho for each pixel of the image. The method was tested on
      five remote sensing images acquired by an airborne sensor under different
      geometric conditions to evaluate the reliability of the method. The results,
      tau(550) and rho, retrieved from each image were validated with field data
      contemporaneously acquired by a sun-sky radiometer and a spectroradiometer,
      respectively. Good correlation index, r, and low root mean square deviations,
      RMSD, were obtained for the tau(550) retrieved by Module A (r(2) = 0.75, RMSD =
      0.08) and the rho retrieved by Module B (r(2) <= 0.9, RMSD <= 0.003). Overall,
      the results are encouraging, indicating that the method is reliable for optical
      atmospheric studies and the atmospheric correction of airborne hyperspectral
      images. The method does not require additional at-ground measurements about at
      ground reflectance of the reference pixel and aerosol optical thickness.

PMID- 22163559
TI  - Enzyme immobilization strategies and electropolymerization conditions to control
      sensitivity and selectivity parameters of a polymer-enzyme composite glucose
      biosensor.
AB  - In an ongoing programme to develop characterization strategies relevant to
      biosensors for in-vivo monitoring, glucose biosensors were fabricated by
      immobilizing the enzyme glucose oxidase (GOx) on 125 MUm diameter Pt cylinder
      wire electrodes (Pt(C)), using three different methods: before, after or during
      the amperometric electrosynthesis of poly(ortho-phenylenediamine), PoPD, which
      also served as a permselective membrane. These electrodes were calibrated with
      H(2)O(2) (the biosensor enzyme signal molecule), glucose, and the archetypal
      interference compound ascorbic acid (AA) to determine the relevant polymer
      permeabilities and the apparent Michaelis-Menten parameters for glucose. A number
      of selectivity parameters were used to identify the most successful design in
      terms of the balance between substrate sensitivity and interference blocking. For
      biosensors electrosynthesized in neutral buffer under the present conditions,
      entrapment of the GOx within the PoPD layer produced the design (Pt(C)/PoPD-GOx)
      with the highest linear sensitivity to glucose (5.0 +/- 0.4 MUA cm(-2) mM(-1)),
      good linear range (K(M) = 16 +/- 2 mM) and response time (< 2 s), and the
      greatest AA blocking (99.8% for 1 mM AA). Further optimization showed that
      fabrication of Pt(C)/PoPD-GOx in the absence of added background electrolyte
      (i.e., electropolymerization in unbuffered enzyme-monomer solution) enhanced
      glucose selectivity 3-fold for this one-pot fabrication protocol which provided
      AA-rejection levels at least equal to recent multi-step polymer bilayer biosensor
      designs. Interestingly, the presence of enzyme protein in the polymer layer had
      opposite effects on permselectivity for low and high concentrations of AA,
      emphasizing the value of studying the concentration dependence of interference
      effects which is rarely reported in the literature.

PMID- 22163560
TI  - A colorimetric sensor for qualitative discrimination and quantitative detection
      of volatile amines.
AB  - We have developed a novel colorimetric sensor based on a digital camera and white
      LED illumination. Colorimetric sensor arrays (CSAs) were made from a set of six
      chemically responsive dyes impregnated on an inert substrate plate by solution
      casting. Six common amine aqueous solutions, including dimethylamine,
      triethylamine, diisopropylamine, aniline, cyclohexylamine, and pyridine vaporized
      at 25  degrees C and six health-related trimethylamine (TMA) concentrations
      including 170 ppm, 51 ppm, 8 ppm, 2 ppm, 125 ppb and 50 ppb were analyzed by the
      sensor to test its ability for the qualitative discrimination and quantitative
      detection of volatile amines. We extracted the feature vectors of the CSA's
      response to the analytes from a fusional color space, which was obtained by
      conducting a joint search algorithm of sequential forward selection and
      sequential backward selection (SFS&SBS) based on the linear discriminant criteria
      (LDC) in a mixed color space composed of six common color spaces. The principle
      component analysis (PCA) followed by the hierarchical cluser analysis (HCA) were
      utilized to discriminate 12 analytes. Results showed that the colorimetric sensor
      grouped the six amine vapors and five TMA concentrations correctly, while TMA
      concentrations of 125 ppb and 50 ppb were indiscriminable from each other. The
      limitation of detection (LOD) of the sensor for TMA was found to be lower than 50
      ppb. The CSAs were reusable for TMA concentrations below 8 ppm.

PMID- 22163561
TI  - Fabrication of localized surface plasmon resonance fiber probes using ionic self
      assembled gold nanoparticles.
AB  - An nm-thickness composite gold thin film consisting of gold nanoparticles and
      polyelectrolytes is fabricated through ionic self-assembled multilayers (ISAM)
      technique and is deposited on end-faces of optical fibers to construct localized
      surface plasmon resonance (LSPR) fiber probes. We demonstrate that the LSPR
      spectrum induced by ISAM gold films can be fine-tuned through the ISAM procedure.
      We investigate variations of reflection spectra of the probe with respect to the
      layer-by-layer adsorption of ISAMs onto end-faces of fibers, and study the
      spectral variation mechanism. Finally, we demonstrated using this fiber probe to
      detect the biotin-streptavidin bioconjugate pair. ISAM adsorbed on optical fibers
      potentially provides a simple, fast, robust, and low-cost, platform for LSPR
      biosensing applications.

PMID- 22163562
TI  - Semiconducting polymer photodetectors with electron and hole blocking layers:
      high detectivity in the near-infrared.
AB  - Sensing from the ultraviolet-visible to the infrared is critical for a variety of
      industrial and scientific applications. Photodetectors with broad spectral
      response, from 300 nm to 1,100 nm, were fabricated using a narrow-band gap
      semiconducting polymer blended with a fullerene derivative. By using both an
      electron-blocking layer and a hole-blocking layer, the polymer photodetectors,
      operating at room temperature, exhibited calculated detectivities greater than
      10(13) cm Hz(1/2)/W over entire spectral range with linear dynamic range
      approximately 130 dB. The performance is comparable to or even better than Si
      photodetectors.

PMID- 22163563
TI  - Optimal configuration of redundant inertial sensors for navigation and FDI
      performance.
AB  - This paper considers the optimal sensor configuration for inertial navigation
      systems which have redundant inertial sensors such as gyroscopes and
      accelerometers. We suggest a method to determine the optimal sensor configuration
      which considers both the navigation and FDI performance. Monte Carlo simulations
      are performed to show the performance of the suggested optimal sensor
      configuration method.

PMID- 22163564
TI  - Effects of high-humidity aging on platinum, palladium, and gold loaded tin oxide-
      volatile organic compound sensors.
AB  - This study is an investigation of high-humidity aging effects on the total
      volatile organic compound (T-VOC) gas-sensing properties of platinum, palladium,
      and gold-loaded tin oxide (Pt,Pd,Au/SnO(2)) thick films. The sensor responses of
      the high-humidity aged Pt,Pd,Au/SnO(2), a non-aged Pt,Pd,Au/SnO(2), and a high
      humidity aged Pt/SnO(2) to T-VOC test gas have been measured. The high-humidity
      aging is an effective treatment for resistance to humidity change for the
      Pt,Pd,Au/SnO(2) but not effective for the Pt/SnO(2). The mechanism of the high
      humidity aging effects is discussed based on the change of surface state of the
      SnO(2) particles.

PMID- 22163565
TI  - Bathymetry determination via X-band radar data: a new strategy and numerical
      results.
AB  - This work deals with the question of sea state monitoring using marine X-band
      radar images and focuses its attention on the problem of sea depth estimation. We
      present and discuss a technique to estimate bathymetry by exploiting the
      dispersion relation for surface gravity waves. This estimation technique is based
      on the correlation between the measured and the theoretical sea wave spectra and
      a simple analysis of the approach is performed through test cases with synthetic
      data. More in detail, the reliability of the estimate technique is verified
      through simulated data sets that are concerned with different values of
      bathymetry and surface currents for two types of sea spectrum: JONSWAP and
      Pierson-Moskowitz. The results show how the estimated bathymetry is fairly
      accurate for low depth values, while the estimate is less accurate as the
      bathymetry increases, due to a less significant role of the bathymetry on the sea
      surface waves as the water depth increases.

PMID- 22163567
TI  - Error analysis and measurement uncertainty for a fiber grating strain-temperature
      sensor.
AB  - A fiber grating sensor capable of distinguishing between temperature and strain,
      using a reference and a dual-wavelength fiber Bragg grating, is presented. Error
      analysis and measurement uncertainty for this sensor are studied theoretically
      and experimentally. The measured root mean squared errors for temperature T and
      strain epsilon were estimated to be 0.13  degrees C and 6 MUepsilon,
      respectively. The maximum errors for temperature and strain were calculated as
      0.00155 T + 2.90 * 10(-6) epsilon and 3.59 * 10(-5) epsilon + 0.01887 T,
      respectively. Using the estimation of expanded uncertainty at 95% confidence
      level with a coverage factor of k = 2.205, temperature and strain measurement
      uncertainties were evaluated as 2.60  degrees C and 32.05 MUepsilon,
      respectively. For the first time, to our knowledge, we have demonstrated the
      feasibility of estimating the measurement uncertainty for simultaneous strain
      temperature sensing with such a fiber grating sensor.

PMID- 22163566
TI  - Prospects of nanotechnology in clinical immunodiagnostics.
AB  - Nanostructured materials are promising compounds that offer new opportunities as
      sensing platforms for the detection of biomolecules. Having micrometer-scale
      length and nanometer-scale diameters, nanomaterials can be manipulated with
      current nanofabrication methods, as well as self-assembly techniques, to
      fabricate nanoscale bio-sensing devices. Nanostructured materials possess
      extraordinary physical, mechanical, electrical, thermal and multifunctional
      properties. Such unique properties advocate their use as biomimetic membranes to
      immobilize and modify biomolecules on the surface of nanoparticles. Alignment,
      uniform dispersion, selective growth and diameter control are general parameters
      which play critical roles in the successful integration of nanostructures for the
      fabrication of bioelectronic sensing devices. In this review, we focus on
      different types and aspects of nanomaterials, including their synthesis,
      properties, conjugation with biomolecules and their application in the
      construction of immunosensing devices. Some key results from each cited article
      are summarized by relating the concept and mechanism behind each sensor,
      experimental conditions and the behavior of the sensor under different
      conditions, etc. The variety of nanomaterial-based bioelectronic devices
      exhibiting novel functions proves the unique properties of nanomaterials in such
      sensing devices, which will surely continue to expand in the future. Such
      nanomaterial based devices are expected to have a major impact in clinical
      immunodiagnostics, environmental monitoring, security surveillance and for
      ensuring food safety.

PMID- 22163568
TI  - Design and characterization of a high resolution microfluidic heat flux sensor
      with thermal modulation.
AB  - A complementary metal-oxide semiconductor-compatible process was used in the
      design and fabrication of a suspended membrane microfluidic heat flux sensor with
      a thermopile for the purpose of measuring the heat flow rate. The combination of
      a thirty-junction gold and nickel thermoelectric sensor with an ultralow noise
      preamplifier, a low pass filter, and a lock-in amplifier can yield a resolution
      20 nW with a sensitivity of 461 V/W. The thermal modulation method is used to
      eliminate low-frequency noise from the sensor output, and various amounts of
      fluidic heat were applied to the sensor to investigate its suitability for
      microfluidic applications. For sensor design and analysis of signal output, a
      method of modeling and simulating electro-thermal behavior in a microfluidic heat
      flux sensor with an integrated electronic circuit is presented and validated. The
      electro-thermal domain model was constructed by using system dynamics,
      particularly the bond graph. The electro-thermal domain system model in which the
      thermal and the electrical domains are coupled expresses the heat generation of
      samples and converts thermal input to electrical output. The proposed electro
      thermal domain system model is in good agreement with the measured output voltage
      response in both the transient and the steady state.

PMID- 22163569
TI  - An efficient and compact difference-frequency-generation spectrometer and its
      application to (12)CH(3)D/(12)CH(4) isotope ratio measurements.
AB  - We have developed an efficient and compact 3.4 MUm difference-frequency
      generation spectrometer using a 1.55 MUm distributed feedback (DFB) laser diode,
      a 1.06 MUm DFB laser diode, and a ridge-waveguide periodically poled lithium
      niobate. It is continuously tunable in the 30 cm(-1) span and is applied to
      (12)CH(3)D/(12)CH(4) isotope ratio measurements. The suitable pair of (12)CH(3)D
      nu(4) (p)P(7,6) and (12)CH(4) nu(2)+nu(4) R(6) F(1)((1)) lines enabled us to
      determine their isotope ratio with a precision repeatability of 0.80/00 using a
      sample and a working standard of pure methane with an effective signal averaging
      time of 100 ms.

PMID- 22163571
TI  - Wireless Multimedia Sensor Networks: current trends and future directions.
AB  - Wireless Multimedia Sensor Networks (WMSNs) have emerged and shifted the focus
      from the typical scalar wireless sensor networks to networks with multimedia
      devices that are capable to retrieve video, audio, images, as well as scalar
      sensor data. WMSNs are able to deliver multimedia content due to the availability
      of inexpensive CMOS cameras and microphones coupled with the significant progress
      in distributed signal processing and multimedia source coding techniques. In this
      paper, we outline the design challenges of WMSNs, give a comprehensive discussion
      of the proposed architectures, algorithms and protocols for the different layers
      of the communication protocol stack for WMSNs, and evaluate the existing WMSN
      hardware and testbeds. The paper will give the reader a clear view of the state
      of the art at all aspects of this research area, and shed the light on its main
      current challenges and future trends. We also hope it will foster discussions and
      new research ideas among its researchers.

PMID- 22163570
TI  - Microfluidic systems for biosensing.
AB  - In the past two decades, Micro Fluidic Systems (MFS) have emerged as a powerful
      tool for biosensing, particularly in enriching and purifying molecules and cells
      in biological samples. Compared with conventional sensing techniques, distinctive
      advantages of using MFS for biomedicine include ultra-high sensitivity, higher
      throughput, in-situ monitoring and lower cost. This review aims to summarize the
      recent advancements in two major types of micro fluidic systems, continuous and
      discrete MFS, as well as their biomedical applications. The state-of-the-art of
      active and passive mechanisms of fluid manipulation for mixing, separation,
      purification and concentration will also be elaborated. Future trends of using
      MFS in detection at molecular or cellular level, especially in stem cell therapy,
      tissue engineering and regenerative medicine, are also prospected.

PMID- 22163572
TI  - Electromagnet weight reduction in a magnetic levitation system for contactless
      delivery applications.
AB  - This paper presents an optimum design of a lightweight vehicle levitation
      electromagnet, which also provides a passive guide force in a magnetic levitation
      system for contactless delivery applications. The split alignment of C-shaped
      electromagnets about C-shaped rails has a bad effect on the lateral deviation
      force, therefore, no-split positioning of electromagnets is better for lateral
      performance. This is verified by simulations and experiments. This paper presents
      a statistically optimized design with a high number of the design variables to
      reduce the weight of the electromagnet under the constraint of normal force using
      response surface methodology (RSM) and the kriging interpolation method. 2D and
      3D magnetostatic analysis of the electromagnet are performed using ANSYS. The
      most effective design variables are extracted by a Pareto chart. The most
      desirable set is determined and the influence of each design variable on the
      objective function can be obtained. The generalized reduced gradient (GRG)
      algorithm is adopted in the kriging model. This paper's procedure is validated by
      a comparison between experimental and calculation results, which shows that the
      predicted performance of the electromagnet designed by RSM is in good agreement
      with the simulation results.

PMID- 22163573
TI  - Computational methodology for absolute calibration curves for microfluidic
      optical analyses.
AB  - Optical fluorescence and absorption are two of the primary techniques used for
      analytical microfluidics. We provide a thorough yet tractable method for
      computing the performance of diverse optical micro-analytical systems. Sample
      sizes range from nano- to many micro-liters and concentrations from nano- to
      milli-molar. Equations are provided to trace quantitatively the flow of the
      fundamental entities, namely photons and electrons, and the conversion of energy
      from the source, through optical components, samples and spectral-selective
      components, to the detectors and beyond. The equations permit facile computations
      of calibration curves that relate the concentrations or numbers of molecules
      measured to the absolute signals from the system. This methodology provides the
      basis for both detailed understanding and improved design of microfluidic optical
      analytical systems. It saves prototype turn-around time, and is much simpler and
      faster to use than ray tracing programs. Over two thousand spreadsheet
      computations were performed during this study. We found that some design
      variations produce higher signal levels and, for constant noise levels, lower
      minimum detection limits. Improvements of more than a factor of 1,000 were
      realized.

PMID- 22163574
TI  - "Smart" continuous glucose monitoring sensors: on-line signal processing issues.
AB  - The availability of continuous glucose monitoring (CGM) sensors allows
      development of new strategies for the treatment of diabetes. In particular, from
      an on-line perspective, CGM sensors can become "smart" by providing them with
      algorithms able to generate alerts when glucose concentration is predicted to
      exceed the normal range thresholds. To do so, at least four important aspects
      have to be considered and dealt with on-line. First, the CGM data must be
      accurately calibrated. Then, CGM data need to be filtered in order to enhance
      their signal-to-noise ratio (SNR). Thirdly, predictions of future glucose
      concentration should be generated with suitable modeling methodologies. Finally,
      generation of alerts should be done by minimizing the risk of detecting false and
      missing true events. For these four challenges, several techniques, with various
      degrees of sophistication, have been proposed in the literature and are
      critically reviewed in this paper.

PMID- 22163575
TI  - Catalysts as sensors--a promising novel approach in automotive exhaust gas
      aftertreatment.
AB  - Sensors that detect directly and in situ the status of automotive exhaust gas
      catalysts by monitoring the electrical properties of the catalyst coating itself
      are overviewed. Examples included in this review are the in-situ determination of
      the electrical impedance of three-way catalysts based on ceria-zirconia solutions
      and of lean NO(x) traps of earth-alkaline based coatings, as well as approaches
      to determine the ammonia loading in Fe-SCR-zeolites with electrical ac
      measurements. Even more sophisticated approaches based on interactions with
      electromagnetic waves are also reviewed. For that purpose, metallic stick-like
      antennas are inserted into the exhaust pipe. The catalyst properties are measured
      in a contactless manner, directly indicating the catalyst status. The radio
      frequency probes gauge the oxygen loading degree of three-way catalysts, the
      NO(x)-loading of lean NO(x) traps, and the soot loading of Diesel particulate
      filters.

PMID- 22163576
TI  - A microring resonator sensor for sensitive detection of 1,3,5-trinitrotoluene
      (TNT).
AB  - A microring resonator sensor device for sensitive detection of the explosive
      1,3,5-trinitrotoluene (TNT) is presented. It is based on the combination of a
      silicon microring resonator and tailored receptor molecules.

PMID- 22163578
TI  - Voltammetry under a controlled temperature gradient.
AB  - Electrochemical measurements are generally done under isothermal conditions. Here
      we report on the application of a controlled temperature gradient between the
      working electrode surface and the solution. Using electrochemical sensors
      prepared on ceramic materials with extremely high specific heat conductivity, the
      temperature gradient between the electrode and solution was applied here as a
      second driving force. This application of the Soret phenomenon increases the mass
      transfer in the Nernst layer and enables more accurate control of the electrode
      response enhancement by a combination of diffusion and thermal diffusion. We have
      thus studied the effect of Soret phenomenon by cyclic voltammetry measurements in
      ferro/ferricyanide. The time dependence of sensor response disappears when
      applying the Soret phenomenon, and the complicated shape of the cyclic
      voltammogram is replaced by a simple exponential curve. We have derived the
      Cotrell-Soret equation describing the steady-state response with an applied
      temperature difference.

PMID- 22163579
TI  - Optimization of anodized-aluminum pressure-sensitive paint by controlling
      luminophore concentration.
AB  - Anodized-aluminum pressure-sensitive paint (AA-PSP) has been used as a global
      pressure sensor for unsteady flow measurements. We use a dipping deposition
      method to apply a luminophore on a porous anodized-aluminum surface, controlling
      the luminophore concentration of the dipping method to optimize AA-PSP
      characteristics. The concentration is varied from 0.001 to 10 mM.
      Characterizations include the pressure sensitivity, the temperature dependency,
      and the signal level. The pressure sensitivity shows around 60 % at a lower
      concentration up to 0.1 mM. Above this concentration, the sensitivity reduces to
      a half. The temperature dependency becomes more than a half by setting the
      luminophore concentration from 0.001 to 10 mM. There is 3.6-fold change in the
      signal level by varying the concentration. To discuss an optimum concentration, a
      weight coefficient is introduced. We can arbitrarily change the coefficients to
      create an optimized AA-PSP for our sensing purposes.

PMID- 22163577
TI  - Intelligent chiral sensing based on supramolecular and interfacial concepts.
AB  - Of the known intelligently-operating systems, the majority can undoubtedly be
      classed as being of biological origin. One of the notable differences between
      biological and artificial systems is the important fact that biological materials
      consist mostly of chiral molecules. While most biochemical processes routinely
      discriminate chiral molecules, differentiation between chiral molecules in
      artificial systems is currently one of the challenging subjects in the field of
      molecular recognition. Therefore, one of the important challenges for intelligent
      man-made sensors is to prepare a sensing system that can discriminate chiral
      molecules. Because intermolecular interactions and detection at surfaces are
      respectively parts of supramolecular chemistry and interfacial science, chiral
      sensing based on supramolecular and interfacial concepts is a significant topic.
      In this review, we briefly summarize recent advances in these fields, including
      supramolecular hosts for color detection on chiral sensing, indicator
      displacement assays, kinetic resolution in supramolecular reactions with analyses
      by mass spectrometry, use of chiral shape-defined polymers, such as dynamic
      helical polymers, molecular imprinting, thin films on surfaces of devices such as
      QCM, functional electrodes, FET, and SPR, the combined technique of magnetic
      resonance imaging and immunoassay, and chiral detection using scanning tunneling
      microscopy and cantilever technology. In addition, we will discuss novel concepts
      in recent research including the use of achiral reagents for chiral sensing with
      NMR, and mechanical control of chiral sensing. The importance of integration of
      chiral sensing systems with rapidly developing nanotechnology and nanomaterials
      is also emphasized.

PMID- 22163580
TI  - Study on a two-dimensional scanning micro-mirror and its application in a MOEMS
      target detector.
AB  - A two-dimensional (2D) scanning micro-mirror for target detection and measurement
      has been developed. This new micro-mirror is used in a MOEMS target detector to
      replace the conventional scanning detector. The micro-mirror is fabricated by
      MEMS process and actuated by a piezoelectric actuator. To achieve large
      deflection angles, the micro-mirror is excited in the resonance modes. It has two
      degrees of freedom and changes the direction of the emitted laser beam for a
      regional 2D scanning. For the deflection angles measurement, piezoresistors are
      integrated in the micro-mirror and the deflection angles of each direction can be
      detected independently and precisely. Based on the scanning micro-mirror and the
      phase-shift ranging technology, a MOEMS target detector has been developed in a
      size of 90 mm * 35 mm * 50 mm. The experiment shows that the target can be
      detected in the scanning field and the relative range and orientation can be
      measured by the MOEMS target detector. For the target distance up to 3 m with a
      field of view about 20 degrees  * 20 degrees , the measurement resolution is
      about 10.2 cm in range, 0.15 degrees  in the horizontal direction and 0.22
      degrees  in the vertical direction for orientation.

PMID- 22163581
TI  - Quantum cascade laser absorption spectroscopy as a plasma diagnostic tool: an
      overview.
AB  - The recent availability of thermoelectrically cooled pulsed and continuous wave
      quantum and inter-band cascade lasers in the mid-infrared spectral region has led
      to significant improvements and new developments in chemical sensing techniques
      using in-situ laser absorption spectroscopy for plasma diagnostic purposes. The
      aim of this article is therefore two-fold: (i) to summarize the challenges which
      arise in the application of quantum cascade lasers in such environments, and,
      (ii) to provide an overview of recent spectroscopic results (encompassing cavity
      enhanced methods) obtained in different kinds of plasma used in both research and
      industry.

PMID- 22163582
TI  - Position and speed control of brushless DC motors using sensorless techniques and
      application trends.
AB  - This paper provides a technical review of position and speed sensorless methods
      for controlling Brushless Direct Current (BLDC) motor drives, including the
      background analysis using sensors, limitations and advances. The performance and
      reliability of BLDC motor drivers have been improved because the conventional
      control and sensing techniques have been improved through sensorless technology.
      Then, in this paper sensorless advances are reviewed and recent developments in
      this area are introduced with their inherent advantages and drawbacks, including
      the analysis of practical implementation issues and applications. The study
      includes a deep overview of state-of-the-art back-EMF sensing methods, which
      includes Terminal Voltage Sensing, Third Harmonic Voltage Integration, Terminal
      Current Sensing, Back-EMF Integration and PWM strategies. Also, the most relevant
      techniques based on estimation and models are briefly analysed, such as Sliding
      mode Observer, Extended Kalman Filter, Model Reference Adaptive System, Adaptive
      observers (Full-order and Pseudoreduced-order) and Artificial Neural Networks.

PMID- 22163583
TI  - Wireless Sensor Networks for oceanographic monitoring: a systematic review.
AB  - Monitoring of the marine environment has come to be a field of scientific
      interest in the last ten years. The instruments used in this work have ranged
      from small-scale sensor networks to complex observation systems. Among small
      scale networks, Wireless Sensor Networks (WSNs) are a highly attractive solution
      in that they are easy to deploy, operate and dismantle and are relatively
      inexpensive. The aim of this paper is to identify, appraise, select and
      synthesize all high quality research evidence relevant to the use of WSNs in
      oceanographic monitoring. The literature is systematically reviewed to offer an
      overview of the present state of this field of study and identify the principal
      resources that have been used to implement networks of this kind. Finally, this
      article details the challenges and difficulties that have to be overcome if these
      networks are to be successfully deployed.

PMID- 22163585
TI  - L band brightness temperature observations over a corn canopy during the entire
      growth cycle.
AB  - During a field campaign covering the 2002 corn growing season, a dual polarized
      tower mounted L-band (1.4 GHz) radiometer (LRAD) provided brightness temperature
      (T(B)) measurements at preset intervals, incidence and azimuth angles. These
      radiometer measurements were supported by an extensive characterization of land
      surface variables including soil moisture, soil temperature, vegetation biomass,
      and surface roughness. In the period May 22 to August 30, ten days of radiometer
      and ground measurements are available for a corn canopy with a vegetation water
      content (W) range of 0.0 to 4.3 kg m(-2). Using this data set, the effects of
      corn vegetation on surface emissions are investigated by means of a semi
      empirical radiative transfer model. Additionally, the impact of roughness on the
      surface emission is quantified using T(B) measurements over bare soil conditions.
      Subsequently, the estimated roughness parameters, ground measurements and
      horizontally (H)-polarized T(B) are employed to invert the H-polarized
      transmissivity (gamma(h)) for the monitored corn growing season.

PMID- 22163584
TI  - Exploiting the autofluorescent properties of photosynthetic pigments for analysis
      of pigmentation and morphology in live Fremyella diplosiphon cells.
AB  - Fremyella diplosiphon is a freshwater, filamentous cyanobacterium that exhibits
      light-dependent regulation of photosynthetic pigment accumulation and cellular
      and filament morphologies in a well-known process known as complementary
      chromatic adaptation (CCA). One of the techniques used to investigate the
      molecular bases of distinct aspects of CCA is confocal laser scanning microscopy
      (CLSM). CLSM capitalizes on the autofluorescent properties of cyanobacterial
      phycobiliproteins and chlorophyll a. We employed CLSM to perform spectral
      scanning analyses of F. diplosiphon strains grown under distinct light
      conditions. We report optimized utilization of CLSM to elucidate the molecular
      basis of the photoregulation of pigment accumulation and morphological responses
      in F. diplosiphon.

PMID- 22163586
TI  - The effects of the location of Au additives on combustion-generated SnO(2)
      nanopowders for CO gas sensing.
AB  - The current work presents the results of an experimental study of the effects of
      the location of gold additives on the performance of combustion-generated tin
      dioxide (SnO(2)) nanopowders in solid state gas sensors. The time response and
      sensor response to 500 ppm carbon monoxide is reported for a range of gold
      additive/SnO(2) film architectures including the use of colloidal, sputtered, and
      combustion-generated Au additives. The opportunities afforded by combustion
      synthesis to affect the SnO(2)/additive morphology are demonstrated. The best
      sensor performance in terms of sensor response (S) and time response (tau) was
      observed when the Au additives were restricted to the outermost layer of the gas
      sensing film. Further improvement was observed in the sensor response and time
      response when the Au additives were dispersed throughout the outermost layer of
      the film, where S = 11.3 and tau = 51 s, as opposed to Au localized at the
      surface, where S = 6.1 and tau = 60 s.

PMID- 22163587
TI  - Fluorescent chemosensors for toxic organophosphorus pesticides: a review.
AB  - Many organophosphorus (OP) based compounds are highly toxic and powerful
      inhibitors of cholinesterases that generate serious environmental and human
      health concerns. Organothiophosphates with a thiophosphoryl (P=S) functional
      group constitute a broad class of these widely used pesticides. They are related
      to the more reactive phosphoryl (P=O) organophosphates, which include very lethal
      nerve agents and chemical warfare agents, such as, VX, Soman and Sarin.
      Unfortunately, widespread and frequent commercial use of OP-based compounds in
      agricultural lands has resulted in their presence as residues in crops,
      livestock, and poultry products and also led to their migration into aquifers.
      Thus, the design of new sensors with improved analyte selectivity and sensitivity
      is of paramount importance in this area. Herein, we review recent advances in the
      development of fluorescent chemosensors for toxic OP pesticides and related
      compounds. We also discuss challenges and progress towards the design of future
      chemosensors with dual modes for signal transduction.

PMID- 22163588
TI  - Investigation of the frequency shift of a SAD circuit loop and the internal micro
      cantilever in a gas sensor.
AB  - Micro-cantilever sensors for mass detection using resonance frequency have
      attracted considerable attention over the last decade in the field of gas
      sensing. For such a sensing system, an oscillator circuit loop is conventionally
      used to actuate the micro-cantilever, and trace the frequency shifts. In this
      paper, gas experiments are introduced to investigate the mechanical resonance
      frequency shifts of the micro-cantilever within the circuit loop(mechanical
      resonance frequency, MRF) and resonating frequency shifts of the electric signal
      in the oscillator circuit (system working frequency, SWF). A silicon beam with a
      piezoelectric zinc oxide layer is employed in the experiment, and a Self
      Actuating-Detecting (SAD) circuit loop is built to drive the micro-cantilever and
      to follow the frequency shifts. The differences between the two resonating
      frequencies and their shifts are discussed and analyzed, and a coefficient alpha
      related to the two frequency shifts is confirmed.

PMID- 22163589
TI  - Two-channel hyperspectral LiDAR with a supercontinuum laser source.
AB  - Recent advances in nonlinear fiber optics and compact pulsed lasers have resulted
      in creation of broadband directional light sources. These supercontinuum laser
      sources produce directional broadband light using cascaded nonlinear optical
      interactions in an optical fibre framework. This system is used to simultaneously
      measure distance and reflectance to demonstrate a technique capable of
      distinguishing between a vegetation target and inorganic material using the
      Normalized Difference Vegetation Index (NDVI) parameters, while the range can be
      obtained from the waveform of the echoes. A two-channel, spectral range-finding
      system based on a supercontinuum laser source was used to determine its potential
      application of distinguishing the NDVI for Norway spruce, a coniferous tree, and
      its three-dimensional parameters at 600 nm and 800 nm. A prototype system was
      built using commercial components.

PMID- 22163590
TI  - A sensor system for detection of hull surface defects.
AB  - This paper presents a sensor system for detecting defects in ship hull surfaces.
      The sensor was developed to enable a robotic system to perform grit blasting
      operations on ship hulls. To achieve this, the proposed sensor system captures
      images with the help of a camera and processes them in real time using a new
      defect detection method based on thresholding techniques. What makes this method
      different is its efficiency in the automatic detection of defects from images
      recorded in variable lighting conditions. The sensor system was tested under real
      conditions at a Spanish shipyard, with excellent results.

PMID- 22163591
TI  - Volume fraction determination of binary liquid mixtures by measurement of the
      equalization wavelength.
AB  - A method for determination of the volume fraction in binary liquid mixtures by
      measurement of the equalization wavelength of intermodal interference of modes
      LP(01) and LP(11) in a liquid core optical fiber is presented in this paper. This
      method was studied using a liquid core optical fiber with fused silica cladding
      and a core made up of a binary silicon oil/chloroform liquid mixture with
      different volume fractions of chloroform. The interference technique used allows
      us to determine the chloroform volume fraction in the binary mixture with
      accuracy better than 0.1%. One of the most attractive advantages of presented
      method is very small volume of investigated mixture needed, as only a few hundred
      picoliters are necessary for reliable results.

PMID- 22163592
TI  - Development of a fully automated Flow Injection analyzer implementing
      bioluminescent biosensors for water toxicity assessment.
AB  - This paper describes the development of an automated Flow Injection analyzer for
      water toxicity assessment. The analyzer is validated by assessing the toxicity of
      heavy metal (Pb(2+), Hg(2+) and Cu(2+)) solutions. One hundred MUL of a Vibrio
      fischeri suspension are injected in a carrier solution containing different heavy
      metal concentrations. Biosensor cells are mixed with the toxic carrier solution
      in the mixing coil on the way to the detector. Response registered is %
      inhibition of biosensor bioluminescence due to heavy metal toxicity in comparison
      to that resulting by injecting the Vibrio fischeri suspension in deionised water.
      Carrier solutions of mercury showed higher toxicity than the other heavy metals,
      whereas all metals show concentration related levels of toxicity. The biosensor's
      response to carrier solutions of different pHs was tested. Vibrio fischeri's
      bioluminescence is promoted in the pH 5-10 range. Experiments indicate that the
      whole cell biosensor, as applied in the automated fluidic system, responds to
      various toxic solutions.

PMID- 22163593
TI  - Molecular biosensing mechanisms in the spleen for the removal of aged and damaged
      red cells from the blood circulation.
AB  - Heinz bodies are intraerythrocytic inclusions of hemichrome formed as a result of
      hemoglobin (Hb) oxidation. They typically develop in aged red cells. Based on the
      hypothesis that hemichrome formation is an innate characteristic of
      physiologically normal Hb molecules, we present an overview of our previous
      findings regarding the molecular instability of Hb and the formation of
      hemichrome, as well as recent findings on Heinz body formation within normal
      human erythrocytes. Human adult Hb (HbO(2) A) prepared from healthy donors showed
      a tendency to produce hemichrome, even at close to physiological temperature and
      pH. Recent studies found that the number of Heinz bodies formed in red cells
      increased with increasing temperature when freshly drawn venous blood from
      healthy donors was subjected to mild heating above 37  degrees C. These findings
      suggest that Hb molecules control the removal of non-functional erythrocytes from
      the circulation via hemichrome formation and subsequent Heinz body clustering. In
      this review, we discuss the molecular biosensing mechanisms in the spleen, where
      hemichrome formation and subsequent Heinz body clustering within erythrocytes
      play a key role in the removal of aged and damaged red cells from the blood
      circulation.

PMID- 22163594
TI  - Automated signal processing applied to volatile-based inspection of greenhouse
      crops.
AB  - Gas chromatograph-mass spectrometers (GC-MS) have been used and shown utility for
      volatile-based inspection of greenhouse crops. However, a widely recognized
      difficulty associated with GC-MS application is the large and complex data
      generated by this instrument. As a consequence, experienced analysts are often
      required to process this data in order to determine the concentrations of the
      volatile organic compounds (VOCs) of interest. Manual processing is time
      consuming, labour intensive and may be subject to errors due to fatigue. The
      objective of this study was to assess whether or not GC-MS data can also be
      automatically processed in order to determine the concentrations of crop health
      associated VOCs in a greenhouse. An experimental dataset that consisted of twelve
      data files was processed both manually and automatically to address this
      question. Manual processing was based on simple peak integration while the
      automatic processing relied on the algorithms implemented in the MetAlignTM
      software package. The results of automatic processing of the experimental dataset
      resulted in concentrations similar to that after manual processing. These results
      demonstrate that GC-MS data can be automatically processed in order to accurately
      determine the concentrations of crop health associated VOCs in a greenhouse. When
      processing GC-MS data automatically, noise reduction, alignment, baseline
      correction and normalisation are required.

PMID- 22163595
TI  - Reaction force/torque sensing in a master-slave robot system without mechanical
      sensors.
AB  - In human-robot cooperative control systems, force feedback is often necessary in
      order to achieve high precision and high stability. Usually, traditional robot
      assistant systems implement force feedback using force/torque sensors. However,
      it is difficult to directly mount a mechanical force sensor on some working
      terminals, such as in applications of minimally invasive robotic surgery,
      micromanipulation, or in working environments exposed to radiation or high
      temperature. We propose a novel force sensing mechanism for implementing force
      feedback in a master-slave robot system with no mechanical sensors. The system
      consists of two identical electro-motors with the master motor powering the slave
      motor to interact with the environment. A bimanual coordinated training platform
      using the new force sensing mechanism was developed and the system was verified
      in experiments. Results confirm that the proposed mechanism is capable of
      achieving bilateral force sensing and mirror-image movements of two terminals in
      two reverse control directions.

PMID- 22163596
TI  - A piezoelectric plethysmograph sensor based on a Pt wire implanted lead lanthanum
      zirconate titanate bulk ceramic.
AB  - This work reports on the development of a Lead Lanthanum Zirconate Titanate
      (PLZT) bulk ferroelectric poled ceramic structure as a Piezoelectric
      Plethysmograph (PZPG) sensor. The ceramic was implanted during its fabrication
      with a platinum (Pt) wire which works as an internal electrode. The ceramic was
      then submitted to an experimental setup in order to validate and determine the Pt
      wire mechanical effects. This PZPG sensor was also mounted on a finger splint in
      order to measure the blood flow that results from the pulsations of blood
      occurring with each heartbeat. Fingertip pulses were recorded jointly with an ECG
      signal from a 25 year old male to compare the time shift; the PZPG sensor
      guarantees the electrical isolation of the patient. The proposed PZPG has several
      advantages: it can be adjusted for fingertip measurements, but it can easily be
      extended by means of spare bands, therefore making possible PZPG measurements
      from different body locations, e.g., forehead, forearm, knee, neck, etc.

PMID- 22163598
TI  - Adaptive compression of slowly varying images transmitted over Wireless Sensor
      Networks.
AB  - In this article a scheme for image transmission over Wireless Sensor Networks
      (WSN) with an adaptive compression factor is introduced. The proposed control
      architecture affects the quality of the transmitted images according to: (a) the
      traffic load within the network and (b) the level of details contained in an
      image frame. Given an approximate transmission period, the adaptive compression
      mechanism applies Quad Tree Decomposition (QTD) with a varying decomposition
      compression factor based on a gradient adaptive approach. For the initialization
      of the proposed control scheme, the desired a priori maximum bound for the
      transmission time delay is being set, while a tradeoff among the quality of the
      decomposed image frame and the time needed for completing the transmission of the
      frame should be taken under consideration. Based on the proposed control
      mechanism, the quality of the slowly varying transmitted image frames is
      adaptively deviated based on the measured time delay in the transmission. The
      efficacy of the adaptive compression control scheme is validated through extended
      experimental results.

PMID- 22163597
TI  - Detecting solenoid valve deterioration in in-use electronic diesel fuel injection
      control systems.
AB  - The diesel engine is the main power source for most agricultural vehicles. The
      control of diesel engine emissions is an important global issue. Fuel injection
      control systems directly affect fuel efficiency and emissions of diesel engines.
      Deterioration faults, such as rack deformation, solenoid valve failure, and rack
      travel sensor malfunction, are possibly in the fuel injection module of
      electronic diesel control (EDC) systems. Among these faults, solenoid valve
      failure is most likely to occur for in-use diesel engines. According to the
      previous studies, this failure is a result of the wear of the plunger and sleeve,
      based on a long period of usage, lubricant degradation, or engine overheating.
      Due to the difficulty in identifying solenoid valve deterioration, this study
      focuses on developing a sensor identification algorithm that can clearly classify
      the usability of the solenoid valve, without disassembling the fuel pump of an
      EDC system for in-use agricultural vehicles. A diagnostic algorithm is proposed,
      including a feedback controller, a parameter identifier, a linear variable
      differential transformer (LVDT) sensor, and a neural network classifier.
      Experimental results show that the proposed algorithm can accurately identify the
      usability of solenoid valves.

PMID- 22163599
TI  - Performance evaluation of triangulation based range sensors.
AB  - The performance of 2D digital imaging systems depends on several factors related
      with both optical and electronic processing. These concepts have originated
      standards, which have been conceived for photographic equipment and bi
      dimensional scanning systems, and which have been aimed at estimating different
      parameters such as resolution, noise or dynamic range. Conversely, no standard
      test protocols currently exist for evaluating the corresponding performances of
      3D imaging systems such as laser scanners or pattern projection range cameras.
      This paper is focused on investigating experimental processes for evaluating some
      critical parameters of 3D equipment, by extending the concepts defined by the ISO
      standards to the 3D domain. The experimental part of this work concerns the
      characterization of different range sensors through the extraction of their
      resolution, accuracy and uncertainty from sets of 3D data acquisitions of
      specifically designed test objects whose geometrical characteristics are known in
      advance. The major objective of this contribution is to suggest an easy
      characterization process for generating a reliable comparison between the
      performances of different range sensors and to check if a specific piece of
      equipment is compliant with the expected characteristics.

PMID- 22163600
TI  - Correlating multimodal physical sensor information with biological analysis in
      ultra endurance cycling.
AB  - The sporting domain has traditionally been used as a testing ground for new
      technologies which subsequently make their way into the public domain. This
      includes sensors. In this article a range of physical and biological sensors
      deployed in a 64 hour ultra-endurance non-stop cycling race are described. A
      novel algorithm to estimate the energy expenditure while cycling and resting
      during the event are outlined. Initial analysis in this noisy domain of "sensors
      in the field" are very encouraging and represent a first with respect to cycling.

PMID- 22163601
TI  - Wireless Sensor Network deployment for monitoring wildlife passages.
AB  - Wireless Sensor Networks (WSNs) are being deployed in very diverse application
      scenarios, including rural and forest environments. In these particular contexts,
      specimen protection and conservation is a challenge, especially in natural
      reserves, dangerous locations or hot spots of these reserves (i.e., roads,
      railways, and other civil infrastructures). This paper proposes and studies a WSN
      based system for generic target (animal) tracking in the surrounding area of
      wildlife passages built to establish safe ways for animals to cross
      transportation infrastructures. In addition, it allows target identification
      through the use of video sensors connected to strategically deployed nodes. This
      deployment is designed on the basis of the IEEE 802.15.4 standard, but it
      increases the lifetime of the nodes through an appropriate scheduling. The system
      has been evaluated for the particular scenario of wildlife monitoring in passages
      across roads. For this purpose, different schemes have been simulated in order to
      find the most appropriate network operational parameters. Moreover, a novel
      prototype, provided with motion detector sensors, has also been developed and its
      design feasibility demonstrated. Original software modules providing new
      functionalities have been implemented and included in this prototype. Finally,
      main performance evaluation results of the whole system are presented and
      discussed in depth.

PMID- 22163602
TI  - A field programmable gate array-based reconfigurable smart-sensor network for
      wireless monitoring of new generation computer numerically controlled machines.
AB  - Computer numerically controlled (CNC) machines have evolved to adapt to
      increasing technological and industrial requirements. To cover these needs, new
      generation machines have to perform monitoring strategies by incorporating
      multiple sensors. Since in most of applications the online Processing of the
      variables is essential, the use of smart sensors is necessary. The contribution
      of this work is the development of a wireless network platform of reconfigurable
      smart sensors for CNC machine applications complying with the measurement
      requirements of new generation CNC machines. Four different smart sensors are put
      under test in the network and their corresponding signal processing techniques
      are implemented in a Field Programmable Gate Array (FPGA)-based sensor node.

PMID- 22163603
TI  - Experimental demonstration of masking phenomena between competing odorants via an
      air dilution sensory test.
AB  - To simulate the occurrence of masking phenomena with the aid of an air dilution
      sensory (ads) test, two types of odorant mixtures were prepared: (1) M(2) with
      two individual odorants [H(2)S and acetaldehyde (AA)] and (2) M(6) with six
      individual odorants (H(2)S and five aldehydes). The test results derived for
      samples containing single individual odorants at a wide range of concentrations
      are initially used to define the empirical relationship between the dilution-to
      threshold (D/T) ratio and odor intensity (OI) scaling. Based on these
      relationships, the D/T ratios were estimated for each odorant with the same
      intensity as the synthetic mixture. The relative contribution of each odorant to
      such mixture is then assessed by comparing the estimated and measured D/T values.
      This stepwise test confirmed the dominance of certain compounds at a given OI
      rating. In the case of M(2), H(2)S showed sensitive detection at high OI range,
      while AA did so at low end. The pattern of a competing relationship is also seen
      consistently from M(6) between AA (low) and iso-valeraldehyde (IA: high OI
      range). The overall results thus suggest that the masking phenomena between
      strong odorants should proceed under competing relationships, if released at the
      same time.

PMID- 22163604
TI  - Visual control of robots using range images.
AB  - In the last years, 3D-vision systems based on the time-of-flight (ToF) principle
      have gained more importance in order to obtain 3D information from the workspace.
      In this paper, an analysis of the use of 3D ToF cameras to guide a robot arm is
      performed. To do so, an adaptive method to simultaneous visual servo control and
      camera calibration is presented. Using this method a robot arm is guided by using
      range information obtained from a ToF camera. Furthermore, the self-calibration
      method obtains the adequate integration time to be used by the range camera in
      order to precisely determine the depth information.

PMID- 22163605
TI  - Small molecule immunosensing using surface plasmon resonance.
AB  - Surface plasmon resonance (SPR) biosensors utilize refractive index changes to
      sensitively detect mass changes at noble metal sensor surface interfaces. As
      such, they have been extensively applied to immunoassays of large molecules,
      where their high mass and use of sandwich immunoassay formats can result in
      excellent sensitivity. Small molecule immunosensing using SPR is more
      challenging. It requires antibodies or high-mass or noble metal labels to provide
      the required signal for ultrasensitive assays. Also, it can suffer from steric
      hindrance between the small antigen and large antibodies. However, new studies
      are increasingly meeting these and other challenges to offer highly sensitive
      small molecule immunosensor technologies through careful consideration of sensor
      interface design and signal enhancement. This review examines the application of
      SPR transduction technologies to small molecule immunoassays directed to
      different classes of small molecule antigens, including the steroid hormones,
      toxins, drugs and explosives residues. Also considered are the matrix effects
      resulting from measurement in chemically complex samples, the construction of
      stable sensor surfaces and the development of multiplexed assays capable of
      detecting several compounds at once. Assay design approaches are discussed and
      related to the sensitivities obtained.

PMID- 22163606
TI  - Location-aware dynamic session-key management for grid-based Wireless Sensor
      Networks.
AB  - Security is a critical issue for sensor networks used in hostile environments.
      When wireless sensor nodes in a wireless sensor network are distributed in an
      insecure hostile environment, the sensor nodes must be protected: a secret key
      must be used to protect the nodes transmitting messages. If the nodes are not
      protected and become compromised, many types of attacks against the network may
      result. Such is the case with existing schemes, which are vulnerable to attacks
      because they mostly provide a hop-by-hop paradigm, which is insufficient to
      defend against known attacks. We propose a location-aware dynamic session-key
      management protocol for grid-based wireless sensor networks. The proposed
      protocol improves the security of a secret key. The proposed scheme also includes
      a key that is dynamically updated. This dynamic update can lower the probability
      of the key being guessed correctly. Thus currently known attacks can be defended.
      By utilizing the local information, the proposed scheme can also limit the
      flooding region in order to reduce the energy that is consumed in discovering
      routing paths.

PMID- 22163607
TI  - Use of a multiplexed CMOS microarray to optimize and compare oligonucleotide
      binding to DNA probes synthesized or immobilized on individual electrodes.
AB  - The CombiMatrix microarray with 12,544 electrodes supports in situ
      electrochemical synthesis of user-defined DNA probes. As an alternative, we
      immobilized commercially synthesized DNA probes on individual electrodes coated
      with electropolymerized polypyrrole (Ppy). Hybridization was measured using a
      biotinylated target oligonucleotide and either Cy5-streptavidin and fluorescence
      detection or horseradish peroxidase-streptavidin and enzyme-enhanced
      electrochemical detection. Detection efficiencies were optimized by varying the
      deposition of the Ppy, the terminal groups on the DNA probes, and other factors
      that impacted fluorescence quenching and electrical conductivity. Optimized
      results were compared against those obtained using a microarray with the same DNA
      sequences synthesized in situ. Immobilized probes produced higher fluorescence
      signals, possibly by providing a greater stand off between the Cy5 on the target
      oligonucleotide and the quenching effects of the Ppy and the platinum electrode.

PMID- 22163608
TI  - Observing the forest canopy with a new ultra-violet compact airborne lidar.
AB  - We have developed a new airborne UV lidar for the forest canopy and deployed it
      in the Landes forest (France). It is the first one that: (i) operates at 355 nm
      for emitting energetic pulses of 16 mJ at 20 Hz while fulfilling eye-safety
      regulations and (ii) is flown onboard an ultra-light airplane for enhanced flight
      flexibility. Laser footprints at ground level were 2.4 m wide for a flying
      altitude of 300 m. Three test areas of ~ 500 * 500 m(2) with Maritime pines of
      different ages were investigated. We used a threshold method adapted for this
      lidar to accurately extract from its waveforms detailed forest canopy vertical
      structure: canopy top, tree crown base and undergrowth heights. Good detection
      sensitivity enabled the observation of ground returns underneath the trees.
      Statistical and one-to-one comparisons with ground measurements by field
      foresters indicated a mean absolute accuracy of ~ 1 m. Sensitivity tests on
      detection threshold showed the importance of signal to noise ratio and footprint
      size for a proper detection of the canopy vertical structure. This UV-lidar is
      intended for future innovative applications of simultaneous observation of forest
      canopy, laser-induced vegetation fluorescence and atmospheric aerosols.

PMID- 22163610
TI  - High accuracy acoustic relative humidity measurement in duct flow with air.
AB  - An acoustic relative humidity sensor for air-steam mixtures in duct flow is
      designed and tested. Theory, construction, calibration, considerations on dynamic
      response and results are presented. The measurement device is capable of
      measuring line averaged values of gas velocity, temperature and relative humidity
      (RH) instantaneously, by applying two ultrasonic transducers and an array of four
      temperature sensors. Measurement ranges are: gas velocity of 0-12 m/s with an
      error of +/- 0.13 m/s, temperature 0-100  degrees C with an error of +/- 0.07 
      degrees C and relative humidity 0-100% with accuracy better than 2 % RH above 50 
      degrees C. Main advantage over conventional humidity sensors is the high
      sensitivity at high RH at temperatures exceeding 50  degrees C, with accuracy
      increasing with increasing temperature. The sensors are non-intrusive and resist
      highly humid environments.

PMID- 22163609
TI  - Use of sensors in the treatment and follow-up of patients with diabetes mellitus.
AB  - Glucose control is the cornerstone of Diabetes Mellitus (DM) treatment. Although
      self-regulation using capillary glycemia (SRCG) still remains the best procedure
      in clinical practice, continuous glucose monitoring systems (CGM) offer the
      possibility of continuous and dynamic assessment of interstitial glucose
      concentration. CGM systems have the potential to improve glycemic control while
      decreasing the incidence of hypoglycemia but the efficiency, compared with SRCG,
      is still debated. CGM systems have the greatest potential value in patients with
      hypoglycemic unawareness and in controlling daily fluctuations in blood glucose.
      The implementation of continuous monitoring in the standard clinical setting has
      not yet been established but a new generation of open and close loop subcutaneous
      insulin infusion devices are emerging making insulin treatment and glycemic
      control more reliable.

PMID- 22163611
TI  - Laser induced breakdown spectroscopy for elemental analysis in environmental,
      cultural heritage and space applications: a review of methods and results.
AB  - Analytical applications of Laser Induced Breakdown Spectroscopy (LIBS), namely
      optical emission spectroscopy of laser-induced plasmas, have been constantly
      growing thanks to its intrinsic conceptual simplicity and versatility.
      Qualitative and quantitative analysis can be performed by LIBS both by drawing
      calibration lines and by using calibration-free methods and some of its features,
      so as fast multi-elemental response, micro-destructiveness, instrumentation
      portability, have rendered it particularly suitable for analytical applications
      in the field of environmental science, space exploration and cultural heritage.
      This review reports and discusses LIBS achievements in these areas and results
      obtained for soils and aqueous samples, meteorites and terrestrial samples
      simulating extraterrestrial planets, and cultural heritage samples, including
      buildings and objects of various kinds.

PMID- 22163612
TI  - Development and implementation of image-based algorithms for measurement of
      deformations in material testing.
AB  - This paper presents the development and implementation of three image-based
      methods used to detect and measure the displacements of a vast number of points
      in the case of laboratory testing on construction materials. Starting from the
      needs of structural engineers, three ad hoc tools for crack measurement in fibre
      reinforced specimens and 2D or 3D deformation analysis through digital images
      were implemented and tested. These tools make use of advanced image processing
      algorithms and can integrate or even substitute some traditional sensors employed
      today in most laboratories. In addition, the automation provided by the
      implemented software, the limited cost of the instruments and the possibility to
      operate with an indefinite number of points offer new and more extensive analysis
      in the field of material testing. Several comparisons with other traditional
      sensors widely adopted inside most laboratories were carried out in order to
      demonstrate the accuracy of the implemented software. Implementation details,
      simulations and real applications are reported and discussed in this paper.

PMID- 22163613
TI  - T-Patterns revisited: mining for temporal patterns in sensor data.
AB  - The trend to use large amounts of simple sensors as opposed to a few complex
      sensors to monitor places and systems creates a need for temporal pattern mining
      algorithms to work on such data. The methods that try to discover re-usable and
      interpretable patterns in temporal event data have several shortcomings. We
      contrast several recent approaches to the problem, and extend the T-Pattern
      algorithm, which was previously applied for detection of sequential patterns in
      behavioural sciences. The temporal complexity of the T-pattern approach is
      prohibitive in the scenarios we consider. We remedy this with a statistical model
      to obtain a fast and robust algorithm to find patterns in temporal data. We test
      our algorithm on a recent database collected with passive infrared sensors with
      millions of events.

PMID- 22163614
TI  - A software architecture for adaptive modular sensing systems.
AB  - By combining a number of simple transducer modules, an arbitrarily complex
      sensing system may be produced to accommodate a wide range of applications. This
      work outlines a novel software architecture and knowledge representation scheme
      that has been developed to support this type of flexible and reconfigurable
      modular sensing system. Template algorithms are used to embed intelligence within
      each module. As modules are added or removed, the composite sensor is able to
      automatically determine its overall geometry and assume an appropriate collective
      identity. A virtual machine-based middleware layer runs on top of a real-time
      operating system with a pre-emptive kernel, enabling platform-independent
      template algorithms to be written once and run on any module, irrespective of its
      underlying hardware architecture. Applications that may benefit from easily
      reconfigurable modular sensing systems include flexible inspection, mobile
      robotics, surveillance, and space exploration.

PMID- 22163615
TI  - Bayesian model for matching the radiometric measurements of aerospace and field
      ocean color sensors.
AB  - A Bayesian model is developed to match aerospace ocean color observation to field
      measurements and derive the spatial variability of match-up sites. The
      performance of the model is tested against populations of synthesized spectra and
      full and reduced resolutions of MERIS data. The model derived the scale
      difference between synthesized satellite pixel and point measurements with R(2) >
      0.88 and relative error < 21% in the spectral range from 400 nm to 695 nm. The
      sub-pixel variabilities of reduced resolution MERIS image are derived with less
      than 12% of relative errors in heterogeneous region. The method is generic and
      applicable to different sensors.

PMID- 22163616
TI  - Detecting abnormal vehicular dynamics at intersections based on an unsupervised
      learning approach and a stochastic model.
AB  - This investigation demonstrates an unsupervised approach for modeling traffic
      flow and detecting abnormal vehicle behaviors at intersections. In the first
      stage, the approach reveals and records the different states of the system. These
      states are the result of coding and grouping the historical motion of vehicles as
      long binary strings. In the second stage, using sequences of the recorded states,
      a stochastic graph model based on a Markovian approach is built. A behavior is
      labeled abnormal when current motion pattern cannot be recognized as any state of
      the system or a particular sequence of states cannot be parsed with the
      stochastic model. The approach is tested with several sequences of images
      acquired from a vehicular intersection where the traffic flow and duration used
      in connection with the traffic lights are continuously changed throughout the
      day. Finally, the low complexity and the flexibility of the approach make it
      reliable for use in real time systems.

PMID- 22163617
TI  - Efficacy of a computerized sensor system for evaluation and training of dizzy
      patients.
AB  - Patients with vestibular hypofunction often experience dizziness and unsteadiness
      while moving their heads. Appropriate sensors can effectively detect a patient's
      dynamic visual acuity and associated body balance control. Forty-one vestibular
      deficit patients and 10 normal individuals were invited to participate in this
      study. Questionnaires, clinical assessment scales and objective measures were
      evaluated on participants' first visits. After 12 sessions of training, all
      scales were evaluated again on vestibular-deficit patients. The computerized
      system was composed of sensors, including a gyro and strain gauges, data
      acquisition accessories and LabVIEW software. Results revealed that the system
      could effectively distinguish normal subjects from subjects with vestibular
      deficits. In addition, after a rehabilitation program, subjects' subjective and
      objective performances were significantly improved. Based on our results, we
      concluded that the present system, which uses a gyro and strain gauges, may
      provide an effective method for assessing and treating vestibular-deficit
      patients.

PMID- 22163618
TI  - Dynamic uncertainty for compensated second-order systems.
AB  - The compensation of LTI systems and the evaluation of the according uncertainty
      is of growing interest in metrology. Uncertainty evaluation in metrology ought to
      follow specific guidelines, and recently two corresponding uncertainty evaluation
      schemes have been proposed for FIR and IIR filtering. We employ these schemes to
      compare an FIR and an IIR approach for compensating a second-order LTI system
      which has relevance in metrology. Our results suggest that the FIR approach is
      superior in the sense that it yields significantly smaller uncertainties when
      real-time evaluation of uncertainties is desired.

PMID- 22163619
TI  - A Gaussian Mixture Model-based continuous Boundary Detection for 3D sensor
      networks.
AB  - This paper proposes a high precision Gaussian Mixture Model-based novel Boundary
      Detection 3D (BD3D) scheme with reasonable implementation cost for 3D cases by
      selecting a minimum number of Boundary sensor Nodes (BNs) in continuous moving
      objects. It shows apparent advantages in that two classes of boundary and non
      boundary sensor nodes can be efficiently classified using the model selection
      techniques for finite mixture models; furthermore, the set of sensor readings
      within each sensor node's spatial neighbors is formulated using a Gaussian
      Mixture Model; different from DECOMO [1] and COBOM [2], we also formatted a BN
      Array with an additional own sensor reading to benefit selecting Event BNs (EBNs)
      and non-EBNs from the observations of BNs. In particular, we propose a Thick
      Section Model (TSM) to solve the problem of transition between 2D and 3D. It is
      verified by simulations that the BD3D 2D model outperforms DECOMO and COBOM in
      terms of average residual energy and the number of BNs selected, while the BD3D
      3D model demonstrates sound performance even for sensor networks with low
      densities especially when the value of the sensor transmission range (r) is
      larger than the value of Section Thickness (d) in TSM. We have also rigorously
      proved its correctness for continuous geometric domains and full robustness for
      sensor networks over 3D terrains.

PMID- 22163620
TI  - A reaction-diffusion-based coding rate control mechanism for camera sensor
      networks.
AB  - A wireless camera sensor network is useful for surveillance and monitoring for
      its visibility and easy deployment. However, it suffers from the limited capacity
      of wireless communication and a network is easily overflown with a considerable
      amount of video traffic. In this paper, we propose an autonomous video coding
      rate control mechanism where each camera sensor node can autonomously determine
      its coding rate in accordance with the location and velocity of target objects.
      For this purpose, we adopted a biological model, i.e., reaction-diffusion model,
      inspired by the similarity of biological spatial patterns and the spatial
      distribution of video coding rate. Through simulation and practical experiments,
      we verify the effectiveness of our proposal.

PMID- 22163621
TI  - Flat-cladding fiber Bragg grating sensors for large strain amplitude fatigue
      tests.
AB  - We have successfully developed a flat-cladding fiber Bragg grating sensor for
      large cyclic strain amplitude tests of up to +/- 8,000 MUepsilon. The increased
      contact area between the flat-cladding fiber and substrate, together with the
      application of a new bonding process, has significantly increased the bonding
      strength. In the push-pull fatigue tests of an aluminum alloy, the plastic strain
      amplitudes measured by three optical fiber sensors differ only by 0.43% at a
      cyclic strain amplitude of +/- 7,000 MUepsilon and 1.9% at a cyclic strain
      amplitude of +/- 8,000 MUepsilon. We also applied the sensor on an extruded
      magnesium alloy for evaluating the peculiar asymmetric hysteresis loops. The
      results obtained were in good agreement with those measured from the
      extensometer, a further validation of the sensor.

PMID- 22163622
TI  - Mobile calibration based on laser metrology and approximation networks.
AB  - A mobile calibration technique for three-dimensional vision is presented. In this
      method, vision parameters are computed automatically by approximation networks
      built based on the position of a camera and image processing of a laser line. The
      networks also perform three-dimensional visualization. In the proposed system,
      the setup geometry can be modified online, whereby an online re-calibration is
      performed based on data provided by the network and the required modifications of
      extrinsic and intrinsic parameters are thus determined, overcoming any
      calibration limitations caused by the modification procedure. The mobile
      calibration also avoids procedures involving references, which are used in
      traditional online re-calibration methods. The proposed mobile calibration thus
      improves the accuracy and performance of the three-dimensional vision because
      online data of calibrated references are not passed on to the vision system. This
      work represents a contribution to the field of online re-calibration, as verified
      by a comparison with the results based on lighting methods, which are calibrated
      and re-calibrated via perspective projection. Processing time is also studied.

PMID- 22163623
TI  - Multi-walled carbon nanotube-doped tungsten oxide thin films for hydrogen gas
      sensing.
AB  - In this work we have fabricated hydrogen gas sensors based on undoped and 1 wt%
      multi-walled carbon nanotube (MWCNT)-doped tungsten oxide (WO(3)) thin films by
      means of the powder mixing and electron beam (E-beam) evaporation technique.
      Hydrogen sensing properties of the thin films have been investigated at different
      operating temperatures and gas concentrations ranging from 100 ppm to 50,000 ppm.
      The results indicate that the MWCNT-doped WO(3) thin film exhibits high
      sensitivity and selectivity to hydrogen. Thus, MWCNT doping based on E-beam co
      evaporation was shown to be an effective means of preparing hydrogen gas sensors
      with enhanced sensing and reduced operating temperatures. Creation of
      nanochannels and formation of p-n heterojunctions were proposed as the sensing
      mechanism underlying the enhanced hydrogen sensitivity of this hybridized gas
      sensor. To our best knowledge, this is the first report on a MWCNT-doped WO(3)
      hydrogen sensor prepared by the E-beam method.

PMID- 22163624
TI  - A universal intelligent system-on-chip based sensor interface.
AB  - The need for real-time/reliable/low-maintenance distributed monitoring systems,
      e.g., wireless sensor networks, has been becoming more and more evident in many
      applications in the environmental, agro-alimentary, medical, and industrial
      fields. The growing interest in technologies related to sensors is an important
      indicator of these new needs. The design and the realization of complex and/or
      distributed monitoring systems is often difficult due to the multitude of
      different electronic interfaces presented by the sensors available on the market.
      To address these issues the authors propose the concept of a Universal
      Intelligent Sensor Interface (UISI), a new low-cost system based on a single
      commercial chip able to convert a generic transducer into an intelligent sensor
      with multiple standardized interfaces. The device presented offers a flexible
      analog and/or digital front-end, able to interface different transducer
      typologies (such as conditioned, unconditioned, resistive, current output,
      capacitive and digital transducers). The device also provides enhanced processing
      and storage capabilities, as well as a configurable multi-standard output
      interface (including plug-and-play interface based on IEEE 1451.3). In this work
      the general concept of UISI and the design of reconfigurable hardware are
      presented, together with experimental test results validating the proposed
      device.

PMID- 22163625
TI  - Field evaluation of polymer capacitive humidity sensors for Bowen ratio energy
      balance flux measurements.
AB  - The possibility of reliable, reasonably accurate and relatively inexpensive
      estimates of sensible heat and latent energy fluxes was investigated using a
      commercial combination thin-film polymer capacitive relative humidity and
      adjacent temperature sensor instrument. Long-term and unattended water vapour
      pressure profile difference measurements using low-power combination instruments
      were compared with those from a cooled dewpoint mirror hygrometer, the latter
      often used with Bowen ratio energy balance (BREB) systems. An error analysis,
      based on instrument relative humidity and temperature errors, was applied for
      various capacitive humidity instrument models. The main disadvantage of a
      combination capacitive humidity instrument is that two measurements, relative
      humidity and temperature, are required for estimation of water vapour pressure as
      opposed to one for a dewpoint hygrometer. In a laboratory experiment using an
      automated procedure, water vapour pressure differences generated using a
      reference dewpoint generator were measured using a commercial model (Dew-10)
      dewpoint hygrometer and a combination capacitive humidity instrument. The
      laboratory measurement comparisons showed that, potentially, an inexpensive model
      combination capacitive humidity instrument (CS500 or HMP50), or for improved
      results a slightly more expensive model (HMP35C or HMP45C), could substitute for
      the more expensive dewpoint hygrometer. In a field study, in a mesic grassland,
      the water vapour pressure measurement noise for the combination capacitive
      humidity instruments was greater than that for the dewpoint hygrometer. The
      average water vapour pressure profile difference measured using a HMP45C was
      highly correlated with that from a dewpoint hygrometer with a slope less than
      unity. Water vapour pressure measurements using the capacitive humidity
      instruments were not as accurate, compared to those obtained using a dewpoint
      hygrometer, but the resolution magnitudes for the profile difference measurements
      were less than the minimum of 0.01 kPa required for BREB measurements when
      averaged over 20 min. Furthermore, the longer-term capacitive humidity
      measurements are more reliable and not dependent on a sensor bias adjustment as
      is the case for the dewpoint hygrometer. A field comparison of CS500 and HMP45C
      profile water vapour pressure differences yielded a slope of close to unity.
      However, the CS500 exhibited more variable water vapour pressure measurements
      mainly due to its increased variation in temperature measurements compared to the
      HMP45C. Comparisons between 20-min BREB sensible heat fluxes obtained using a
      HMP45C and a dewpoint hygrometer yielded a slope of almost unity. BREB sensible
      heat fluxes measured using a HMP45C were reasonably well correlated with those
      obtained using a surface-layer scintillometer and eddy covariance (slope of
      0.9629 and 0.9198 respectively). This reasonable agreement showed that a
      combination capacitive humidity instrument, with similar relative humidity (RH)
      and temperature error magnitudes of at most 2% RH and 0.3  degrees C
      respectively, and similar measurement time response, would be an adequate and
      less expensive substitute for a dewpoint hygrometer. Furthermore, a combination
      capacitive humidity instrument requires no servicing compared to a dewpoint
      hygrometer which requires a bias adjustment and mirror cleaning each week. These
      findings make unattended BREB measurements of sensible heat flux and evaporation
      cheaper and more reliable with the system easier to assemble and service and with
      reduced instrument power.

PMID- 22163627
TI  - Acute response in vivo of a fiber-optic sensor for continuous glucose monitoring
      from canine studies on point accuracy.
AB  - The objective of this study was to evaluate the acute response of Sencil(TM), a
      fiber-optic sensor, in point accuracy for glucose monitoring in vivo on healthy
      dogs under anesthesia. A total of four dogs with clinically normal glycemia were
      implanted with one sensor each in the chest region to measure the interstitial
      glucose concentration during the ovariohysterectomy procedure. The data was
      acquired every 10 seconds after initiation, and was compared to the concentration
      of venous plasma glucose sampled during the surgery procedures for accuracy of
      agreement analysis. In the four trials with a range of 71-297 mg/dL plasma
      glucose, the collected 21 pairs of ISF readings from the SencilTM and the plasma
      reference showed superior dispersion of residue values than the conventional
      system, and a linear correlation (the Pearson correlation coefficient is 0.9288
      and the y-intercept is 14.22 mg/dL). The MAD (17.6 mg/dL) and RMAD (16.16%) of
      SencilTM measurements were in the comparable range of the conventional system.
      The Clarke error grid analysis indicated that 100% of the paired points were in
      the clinically acceptable zone A (61.9%) and B (38.1%).

PMID- 22163626
TI  - A review of accelerometry-based wearable motion detectors for physical activity
      monitoring.
AB  - Characteristics of physical activity are indicative of one's mobility level,
      latent chronic diseases and aging process. Accelerometers have been widely
      accepted as useful and practical sensors for wearable devices to measure and
      assess physical activity. This paper reviews the development of wearable
      accelerometry-based motion detectors. The principle of accelerometry measurement,
      sensor properties and sensor placements are first introduced. Various research
      using accelerometry-based wearable motion detectors for physical activity
      monitoring and assessment, including posture and movement classification,
      estimation of energy expenditure, fall detection and balance control evaluation,
      are also reviewed. Finally this paper reviews and compares existing commercial
      products to provide a comprehensive outlook of current development status and
      possible emerging technologies.

PMID- 22163628
TI  - Class separation improvements in pixel classification using colour injection.
AB  - This paper presents an improvement in the colour image segmentation in the Hue
      Saturation (HS) sub-space. The authors propose to inject (add) a colour vector in
      the Red Green Blue (RGB) space to increase the class separation in the HS plane.
      The goal of the work is the development of an algorithm to obtain the optimal
      colour vector for injection that maximizes the separation between the classes in
      the HS plane. The chromatic Chrominace-1 Chrominance-2 sub-space (of the
      Luminance Chrominace-1 Chrominance-2 (YC(1)C(2)) space) is used to obtain the
      optimal vector to add. The proposal is applied on each frame of a colour image
      sequence in real-time. It has been tested in applications with reduced contrast
      between the colours of the background and the object, and particularly when the
      size of the object is very small in comparison with the size of the captured
      scene. Numerous tests have confirmed that this proposal improves the segmentation
      process, considerably reducing the effects of the variation of the light
      intensity of the scene. Several tests have been made in skin segmentation in
      applications for sign language recognition via computer vision, where an accurate
      segmentation of hands and face is required.

PMID- 22163629
TI  - Characteristics of ambient volatile organic compounds (VOCs) measured in
      Shanghai, China.
AB  - To better understand the characteristics of ambient abundance of volatile organic
      compounds (VOCs) in Shanghai, one of the biggest metropolis of China, VOCs were
      measured with a gas chromatography system equipped with a mass-selective detector
      (GC/MSD) from July 2006 to February 2010. An intensive measurement campaign was
      conducted (eight samples per day with a 3 hour interval) during May 2009. The
      comparison of ambient VOCs collected in different regions of Shanghai shows that
      the concentrations are slightly higher in the busy commercial area (28.9 ppbv at
      Xujiaui) than in the urban administrative area (24.3 ppbv at Pudong). However,
      during the intensive measurement period, the concentrations in the large steel
      industrial area (28.7 ppbv at Baoshan) were much higher than in the urban
      administrative area (18 ppbv at Pudong), especially for alkanes, alkenes, and
      toluene. The seasonal variations of ambient VOC concentrations measured at the
      Xujiahui sampling site indicate that the VOC concentrations are significantly
      affected by meteorological conditions (such as wind direction and precipitation).
      In addition, although alkanes are the most abundant VOCs at the Xujiahui
      measurement site, the most important VOCs contributing to ozone formation
      potential (OFP) are aromatics, accounting for 57% of the total OFP. The diurnal
      variations of VOC concentrations show that VOC concentrations are higher on
      weekdays than in weekends at the Xujiahui sampling site, suggesting that traffic
      condition and human activities have important impacts on VOC emissions in
      Shanghai. The evidence also shows that the major sources of isoprene are mainly
      resulted from gasoline evaporation at a particular time (06:00-09:00) in the busy
      commercial area. The results gained from this study provide useful information
      for better understanding the characteristics of ambient VOCs and the sources of
      VOCs in Shanghai.

PMID- 22163631
TI  - Non invasive sensors for monitoring the efficiency of AC electrical rotating
      machines.
AB  - This paper presents a non invasive method for estimating the energy efficiency of
      induction motors used in industrial applications. This method is innovative
      because it is only based on the measurement of the external field emitted by the
      motor. The paper describes the sensors used, how they should be placed around the
      machine in order to decouple the external field components generated by both the
      air gap flux and the winding end-windings. The study emphasizes the influence of
      the eddy currents flowing in the yoke frame on the sensor position. A method to
      estimate the torque from the external field use is proposed. The measurements are
      transmitted by a wireless module (Zig-Bee) and they are centralized and stored on
      a PC computer.

PMID- 22163630
TI  - Flame-spray-made undoped zinc oxide films for gas sensing applications.
AB  - Using zinc naphthenate dissolved in xylene as a precursor undoped ZnO nanopowders
      were synthesized by the flame spray pyrolysis technique. The average diameter and
      length of ZnO spherical and hexagonal particles were in the range of 5 to 20 nm,
      while ZnO nanorods were found to be 5-20 nm wide and 20-40 nm long, under 5/5
      (precursor/oxygen) flame conditions. The gas sensitivity of the undoped ZnO
      nanopowders towards 50 ppm of NO(2), C(2)H(5)OH and SO(2) were found to be 33, 7
      and 3, respectively. The sensors showed a great selectivity towards NO(2) at high
      working temperature (at 300  degrees C), while small resistance variations were
      observed for C(2)H(5)OH and SO(2), respectively.

PMID- 22163632
TI  - Effective fingerprint quality estimation for diverse capture sensors.
AB  - Recognizing the quality of fingerprints in advance can be beneficial for
      improving the performance of fingerprint recognition systems. The representative
      features to assess the quality of fingerprint images from different types of
      capture sensors are known to vary. In this paper, an effective quality estimation
      system that can be adapted for different types of capture sensors is designed by
      modifying and combining a set of features including orientation certainty, local
      orientation quality and consistency. The proposed system extracts basic features,
      and generates next level features which are applicable for various types of
      capture sensors. The system then uses the Support Vector Machine (SVM) classifier
      to determine whether or not an image should be accepted as input to the
      recognition system. The experimental results show that the proposed method can
      perform better than previous methods in terms of accuracy. In the meanwhile, the
      proposed method has an ability to eliminate residue images from the optical and
      capacitive sensors, and the coarse images from thermal sensors.

PMID- 22163633
TI  - Sensory evaluation of pralines containing different honey products.
AB  - In this study, pralines manufactured by hand were evaluated sensorially. These
      pralines were obtained from dark chocolate containing 60% cocoa components,
      filled with Apis mellifera carnica Poll drone larvae, blossom honey and a blossom
      honey/pollen mixture from the protected region of Stara Planina-Eastern Serbia (a
      specific botanical region). The objectives of this study were investigations
      related to the use of sensory analysis for quality assessment of new functional
      products with potential benefits for human health, in particular of desserts
      based on dark chocolate pralines filled with different bee products characterized
      by a specific botanical and geographic origin, as well as of their storage
      properties and expected shelf life. Sensory quality (appearance, texture, odor
      and taste were evaluated by a group of experienced panelists immediately after
      the production (day 0), and then after 30, 90 and 180 days of storage under
      ambient conditions (temperature 18-20  degrees C). The results were statistically
      analyzed by the two-factorial analysis of variance (MANOVA) and with the LSD
      test. It is possible to conclude that the storage time and composition of dark
      chocolate pralines containing different honey-bee products have statistically
      highly significant (p < 0.01) influence on the sensorially evaluated properties
      of pralines.

PMID- 22163634
TI  - Flexible temperature sensors on fibers.
AB  - The aim of this paper is to present research dedicated to the elaboration of
      novel, miniaturized flexible temperature sensors for textronic applications.
      Examined sensors were manufactured on a single yarn, which ensures their high
      flexibility and good compatibility with textiles. Stable and linear
      characteristics were obtained by special technological process and applied
      temperature profiles. As a thermo-sensitive materials the innovative polymer
      compositions filled with multiwalled carbon nanotubes were used. Elaborated
      material was adapted to printing and dip-coating techniques to produce NTC
      composites. Nanotube sensors were free from tensometric effect typical for other
      carbon-polymer sensor, and demonstrated TCR of 0.13%/K. Obtained temperature
      sensors, compatible with textile structure, can be applied in rapidly developing
      smart textiles and be used for health and protections purposes.

PMID- 22163636
TI  - A fluorescent thermometer based on a pyrene-labeled thermoresponsive polymer.
AB  - Thermoresponsive polymers that undergo a solubility transition by variation of
      the temperature are important materials for the development of 'smart' materials.
      In this contribution we exploit the solubility phase transition of poly(methoxy
      diethylene glycol methacrylate), which is accompanied by a transition from
      hydrophilic to hydrophobic, for the development of a fluorescent thermometer. To
      translate the polymer phase transition into a fluorescent response, the polymer
      was functionalized with pyrene resulting in a change of the emission based on the
      microenvironment. This approach led to a soluble polymeric fluorescent
      thermometer with a temperature range from 11  degrees C to 21  degrees C. The
      polymer phase transition that occurs during sensing is studied in detail by
      dynamic light scattering.

PMID- 22163635
TI  - Recent trends in monitoring of European water framework directive priority
      substances using micro-sensors: a 2007-2009 review.
AB  - This review discusses from a critical perspective the development of new sensors
      for the measurement of priority pollutants targeted in the E.U. Water Framework
      Directive. Significant advances are reported in the paper and their advantages
      and limitations are also discussed. Future perspectives in this area are also
      pointed out in the conclusions. This review covers publications appeared since
      December 2006 (the publication date of the Swift report). Among priority
      substances, sensors for monitoring the four WFD metals represent 81% of published
      papers. None of analyzed publications present a micro-sensor totally validated in
      laboratory, ready for tests under real conditions in the field. The researches
      are mainly focused on the sensing part of the micro-sensors. Nevertheless, the
      main factor limiting micro-sensor applications in the environment is the
      ruggedness of the receptor towards environmental conditions. This point
      constitutes the first technological obstacle to be overcome for any long-term
      field tests.

PMID- 22163637
TI  - Sensors and clinical mastitis--the quest for the perfect alert.
AB  - When cows on dairy farms are milked with an automatic milking system or in high
      capacity milking parlors, clinical mastitis (CM) cannot be adequately detected
      without sensors. The objective of this paper is to describe the performance
      demands of sensor systems to detect CM and evaluats the current performance of
      these sensor systems. Several detection models based on different sensors were
      studied in the past. When evaluating these models, three factors are important:
      performance (in terms of sensitivity and specificity), the time window and the
      similarity of the study data with real farm data. A CM detection system should
      offer at least a sensitivity of 80% and a specificity of 99%. The time window
      should not be longer than 48 hours and study circumstances should be as similar
      to practical farm circumstances as possible. The study design should comprise
      more than one farm for data collection. Since 1992, 16 peer-reviewed papers have
      been published with a description and evaluation of CM detection models. There is
      a large variation in the use of sensors and algorithms. All this makes these
      results not very comparable. There is a also large difference in performance
      between the detection models and also a large variation in time windows used and
      little similarity between study data. Therefore, it is difficult to compare the
      overall performance of the different CM detection models. The sensitivity and
      specificity found in the different studies could, for a large part, be explained
      in differences in the used time window. None of the described studies satisfied
      the demands for CM detection models.

PMID- 22163638
TI  - Using RFID to enhance security in off-site data storage.
AB  - Off-site data storage is one of the most widely used strategies in enterprises of
      all sizes to improve business continuity. In medium-to-large size enterprises,
      the off-site data storage processes are usually outsourced to specialized
      providers. However, outsourcing the storage of critical business information
      assets raises serious security considerations, some of which are usually either
      disregarded or incorrectly addressed by service providers. This article reviews
      these security considerations and presents a radio frequency identification
      (RFID)-based, off-site, data storage management system specifically designed to
      address security issues. The system relies on a set of security mechanisms or
      controls that are arranged in security layers or tiers to balance security
      requirements with usability and costs. The system has been successfully
      implemented, deployed and put into production. In addition, an experimental
      comparison with classical bar-code-based systems is provided, demonstrating the
      system's benefits in terms of efficiency and failure prevention.

PMID- 22163639
TI  - Identifying and tracking pedestrians based on sensor fusion and motion stability
      predictions.
AB  - The lack of trustworthy sensors makes development of Advanced Driver Assistance
      System (ADAS) applications a tough task. It is necessary to develop intelligent
      systems by combining reliable sensors and real-time algorithms to send the
      proper, accurate messages to the drivers. In this article, an application to
      detect and predict the movement of pedestrians in order to prevent an imminent
      collision has been developed and tested under real conditions. The proposed
      application, first, accurately measures the position of obstacles using a two
      sensor hybrid fusion approach: a stereo camera vision system and a laser scanner.
      Second, it correctly identifies pedestrians using intelligent algorithms based on
      polylines and pattern recognition related to leg positions (laser subsystem) and
      dense disparity maps and u-v disparity (vision subsystem). Third, it uses
      statistical validation gates and confidence regions to track the pedestrian
      within the detection zones of the sensors and predict their position in the
      upcoming frames. The intelligent sensor application has been experimentally
      tested with success while tracking pedestrians that cross and move in zigzag
      fashion in front of a vehicle.

PMID- 22163640
TI  - Energy-efficient and fast data gathering protocols for indoor wireless sensor
      networks.
AB  - Wireless Sensor Networks have become an important technology with numerous
      potential applications for the interaction of computers and the physical
      environment in civilian and military areas. In the routing protocols that are
      specifically designed for the applications used by sensor networks, the limited
      available power of the sensor nodes has been taken into consideration in order to
      extend the lifetime of the networks. In this paper, two protocols based on LEACH
      and called R-EERP and S-EERP with base and threshold values are presented. R-EERP
      and S-EERP are two efficient energy aware routing protocols that can be used for
      some critical applications such as detecting dangerous gases (methane, ammonium,
      carbon monoxide, etc.) in an indoor environment. In R-EERP, sensor nodes are
      deployed randomly in a field similar to LEACH. In S-EERP, nodes are deployed
      sequentially in the rooms of the flats of a multi-story building. In both
      protocols, nodes forming clusters do not change during a cluster change time,
      only the cluster heads change. Furthermore, an XOR operation is performed on the
      collected data in order to prevent the sending of the same data sensed by the
      nodes close to each other. Simulation results show that our proposed protocols
      are more energy-efficient than the conventional LEACH protocol.

PMID- 22163641
TI  - Locating sensors for detecting source-to-target patterns of special nuclear
      material smuggling: a spatial information theoretic approach.
AB  - In this paper, a spatial information-theoretic model is proposed to locate
      sensors for detecting source-to-target patterns of special nuclear material (SNM)
      smuggling. In order to ship the nuclear materials from a source location with SNM
      production to a target city, the smugglers must employ global and domestic
      logistics systems. This paper focuses on locating a limited set of fixed and
      mobile radiation sensors in a transportation network, with the intent to maximize
      the expected information gain and minimize the estimation error for the
      subsequent nuclear material detection stage. A Kalman filtering-based framework
      is adapted to assist the decision-maker in quantifying the network-wide
      information gain and SNM flow estimation accuracy.

PMID- 22163642
TI  - Real-time particle mass spectrometry based on resonant micro strings.
AB  - Micro- and nanomechanical resonators are widely being used as mass sensors due to
      their unprecedented mass sensitivity. We present a simple closed-form expression
      which allows a fast and quantitative calculation of the position and mass of
      individual particles placed on a micro or nano string by measuring the resonant
      frequency shifts of the first two bending modes. The method has been tested by
      detecting the mass spectrum of micro particles placed on a micro string. This
      method enables real-time mass spectrometry necessary for applications such as
      personal monitoring devices for the assessment of the exposure dose of airborne
      nanoparticles.

PMID- 22163643
TI  - An efficient Lagrangean relaxation-based object tracking algorithm in wireless
      sensor networks.
AB  - In this paper we propose an energy-efficient object tracking algorithm in
      wireless sensor networks (WSNs). Such sensor networks have to be designed to
      achieve energy-efficient object tracking for any given arbitrary topology. We
      consider in particular the bi-directional moving objects with given frequencies
      for each pair of sensor nodes and link transmission cost. This problem is
      formulated as a 0/1 integer-programming problem. A Lagrangean relaxation-based
      (LR-based) heuristic algorithm is proposed for solving the optimization problem.
      Experimental results showed that the proposed algorithm achieves near
      optimization in energy-efficient object tracking. Furthermore, the algorithm is
      very efficient and scalable in terms of the solution time.

PMID- 22163644
TI  - A magnetostrictive composite-fiber Bragg Grating sensor.
AB  - This paper presents a light and compact optical fiber Bragg Grating sensor for DC
      and AC magnetic field measurements. The fiber is coated by a thick layer of a
      magnetostrictive composite consisting of particles of Terfenol-D dispersed in a
      polymeric matrix. Among the different compositions for the coating that were
      tested, the best magnetostrictive response was obtained using an epoxy resin as
      binder and a 30% volume fraction of Terfenol-D particles with sizes ranging from
      212 to 300 MUm. The effect of a compressive preload in the sensor was also
      investigated. The achieved resolution was 0.4 mT without a preload or 0.3 mT with
      a compressive pre-stress of 8.6 MPa. The sensor was tested at magnetic fields of
      up to 750 mT under static conditions. Dynamic measurements were conducted with a
      magnetic unbalanced four-pole rotor.

PMID- 22163645
TI  - A novel sensing method and sensing algorithm development for a ubiquitous
      network.
AB  - This paper proposes a novel technique which provides energy efficient circuit
      design for sensors networks. The overall system presented requires a minimum
      number of independently communicating sensors and sub-circuits which enable it to
      reduce the power consumption by setting unused sensors to idle. This technique
      reduces hardware requirements, time and interconnection problems with a
      supervisory control. Our proposed algorithm, which hands over the controls to two
      software mangers for the sensing and moving subsystems can greatly improve the
      overall system performance. Based on the experimental results, we observed that
      our system, which is using sensing and moving managers, the four sensors required
      only 3.4 mW power consumption when a robot arm is moved a total distance of 17
      cm. This system is designed for robot applications but could be implemented to
      many other human environments such as "ubiquitous cities", "smart homes", etc.

PMID- 22163646
TI  - The structure of Ca2+ sensor Case16 reveals the mechanism of reaction to low Ca2+
      concentrations.
AB  - Here we report the first crystal structure of a high-contrast genetically encoded
      circularly permuted green fluorescent protein (cpGFP)-based Ca(2+) sensor,
      Case16, in the presence of a low Ca(2+) concentration. The structure reveals the
      positioning of the chromophore within Case16 at the first stage of the Ca(2+)
      dependent response when only two out of four Ca(2+)-binding pockets of calmodulin
      (CaM) are occupied with Ca(2+) ions. In such a "half Ca(2+)-bound state", Case16
      is characterized by an incomplete interaction between its CaM-/M13-domains. We
      also report the crystal structure of the related Ca(2+) sensor Case12 at
      saturating Ca(2+) concentration. Based on this structure, we postulate that cpGFP
      based Ca(2+) sensors can form non-functional homodimers where the CaM-domain of
      one sensor molecule binds symmetrically to the M13-peptide of the partner sensor
      molecule. Case12 and Case16 behavior upon addition of high concentrations of free
      CaM or M13-peptide reveals that the latter effectively blocks the fluorescent
      response of the sensor. We speculate that the demonstrated intermolecular
      interaction with endogenous substrates and homodimerization can impede proper
      functioning of this type of Ca(2+) sensors in living cells.

PMID- 22163647
TI  - Applications of ferro-nanofluid on a micro-transformer.
AB  - An on-chip transformer with a ferrofluid magnetic core has been developed and
      tested. The transformer consists of solenoid-type coil and a magnetic core of
      ferrofluid, with the former fabricated by MEMS technology and the latter by a
      chemical co-precipitation method. The performance of the MEMS transformer with a
      ferrofluid magnetic core was measured and simulated with frequencies ranging from
      100 kHz to 100 MHz. Experimental results reveal that the presence of the
      ferrofluid increases the inductance of coils and the coupling coefficient of
      transformer; however, it also increases the resistance owing to the lag between
      the external magnetic field and the magnetization of the material.

PMID- 22163648
TI  - Micro cantilever movement detection with an amorphous silicon array of position
      sensitive detectors.
AB  - The movement of a micro cantilever was detected via a self constructed portable
      data acquisition prototype system which integrates a linear array of 32 1D
      amorphous silicon position sensitive detectors (PSD). The system was mounted on a
      microscope using a metal structure platform and the movement of the 30 MUm wide
      by 400 MUm long cantilever was tracked by analyzing the signals acquired by the
      32 sensor array electronic readout system and the relevant data algorithm. The
      obtained results show a linear behavior of the photocurrent relating X and Y
      movement, with a non-linearity of about 3%, a spatial resolution of less than 2
      MUm along the lateral dimension of the sensor as well as of less than 3 MUm along
      the perpendicular dimension of the sensor, when detecting just the micro
      cantilever, and a spatial resolution of less than 1 MUm when detecting the
      holding structure.

PMID- 22163649
TI  - Odours influence visually induced emotion: behavior and neuroimaging.
AB  - The present study was conducted to investigate the influence of olfaction on
      subjective valence intensity ratings of visual presentations. Pictures of five
      different categories (baby, flower, erotic, fear and disgust) were presented each
      being associated with five different odour conditions [no odour, low and high
      concentrations of phenylethyl alcohol (positive odour) and low and high
      concentrations of hydrogen sulphide (negative odour)]. Study participants had to
      rate the emotional content of each picture with respect to valence and intensity
      while brain activities were recorded with a whole-cortex magnetoencephalograph
      (MEG). A significant interaction between odour condition and picture category
      with respect to rating performance was found. In particular, positive valence
      intensity ratings related to flowers were increased in positive and negative
      odour conditions. Negative valence intensity ratings related to disgusting
      pictures were also increased in positive and negative odour conditions. The only
      decrease was found in the baby category in the high concentration negative odour
      condition. No behavioural effects were found for the categories erotic and fear.
      Around 300 ms after stimulus onset odour-related brain activity effects were
      found for all picture categories. On the other hand, around 700 ms after stimulus
      onset odour-related brain activity effects occurred only in the flower, fear and
      disgust picture categories. We interpret that early information processing
      demonstrates more pronounced olfactory and visually induced emotion interaction
      than later information processing. Since the early time window more likely
      reflects subconscious information processing we interpret that interaction
      between olfaction and visually induced emotion mostly occurs below the level of
      consciousness. Later, rather conscious information processing, seems to be
      differently influenced by simultaneous olfaction depending on the kind of emotion
      elicited through the sense of vision.

PMID- 22163650
TI  - Assessment of relative accuracy of AHN-2 laser scanning data using planar
      features.
AB  - AHN-2 is the second part of the Actueel Hoogtebestand Nederland project, which
      concerns the acquisition of high-resolution altimetry data over the entire
      Netherlands using airborne laser scanning. The accuracy assessment of laser
      altimetry data usually relies on comparing corresponding tie elements, often
      points or lines, in the overlapping strips. This paper proposes a new approach to
      strip adjustment and accuracy assessment of AHN-2 data by using planar features.
      In the proposed approach a transformation is estimated between two overlapping
      strips by minimizing the distances between points in one strip and their
      corresponding planes in the other. The planes and the corresponding points are
      extracted in an automated segmentation process. The point-to-plane distances are
      used as observables in an estimation model, whereby the parameters of a
      transformation between the two strips and their associated quality measures are
      estimated. We demonstrate the performance of the method for the accuracy
      assessment of the AHN-2 dataset over Zeeland province of The Netherlands. The
      results show vertical offsets of up to 4 cm between the overlapping strips, and
      horizontal offsets ranging from 2 cm to 34 cm.

PMID- 22163651
TI  - The coverage problem in video-based wireless sensor networks: a survey.
AB  - Wireless sensor networks typically consist of a great number of tiny low-cost
      electronic devices with limited sensing and computing capabilities which
      cooperatively communicate to collect some kind of information from an area of
      interest. When wireless nodes of such networks are equipped with a low-power
      camera, visual data can be retrieved, facilitating a new set of novel
      applications. The nature of video-based wireless sensor networks demands new
      algorithms and solutions, since traditional wireless sensor networks approaches
      are not feasible or even efficient for that specialized communication scenario.
      The coverage problem is a crucial issue of wireless sensor networks, requiring
      specific solutions when video-based sensors are employed. In this paper, it is
      surveyed the state of the art of this particular issue, regarding strategies,
      algorithms and general computational solutions. Open research areas are also
      discussed, envisaging promising investigation considering coverage in video-based
      wireless sensor networks.

PMID- 22163652
TI  - Electrochemical glucose sensors--developments using electrostatic assembly and
      carbon nanotubes for biosensor construction.
AB  - In 1962, Clark and Lyons proposed incorporating the enzyme glucose oxidase in the
      construction of an electrochemical sensor for glucose in blood plasma. In their
      application, Clark and Lyons describe an electrode in which a membrane permeable
      to glucose traps a small volume of solution containing the enzyme adjacent to a
      pH electrode, and the presence of glucose is detected by the change in the
      electrode potential that occurs when glucose reacts with the enzyme in this
      volume of solution. Although described nearly 50 years ago, this seminal
      development provides the general structure for constructing electrochemical
      glucose sensors that is still used today. Despite the maturity of the field, new
      developments that explore solutions to the fundamental limitations of
      electrochemical glucose sensors continue to emerge. Here we discuss two
      developments of the last 15 years; confining the enzyme and a redox mediator to a
      very thin molecular films at electrode surfaces by electrostatic assembly, and
      the use of electrodes modified by carbon nanotubes (CNTs) to leverage the
      electrocatalytic effect of the CNTs to reduce the oxidation overpotential of the
      electrode reaction or for the direct electron transport to the enzyme.

PMID- 22163653
TI  - Study of a QCM dimethyl methylphosphonate sensor based on a ZnO-modified nanowire
      structured manganese dioxide film.
AB  - Sensitive, selective and fast detection of chemical warfare agents is necessary
      for anti-terrorism purposes. In our search for functional materials sensitive to
      dimethyl methylphosphonate (DMMP), a simulant of sarin and other toxic
      organophosphorus compounds, we found that zinc oxide (ZnO) modification
      potentially enhances the absorption of DMMP on a manganese dioxide (MnO(2))
      surface. The adsorption behavior of DMMP was evaluated through the detection of
      tiny organophosphonate compounds with quartz crystal microbalance (QCM) sensors
      coated with ZnO-modified MnO(2) nanofibers and pure MnO(2) nanofibers.
      Experimental results indicated that the QCM sensor coated with ZnO-modified
      nanostructured MnO(2) film exhibited much higher sensitivity and better
      selectivity in comparison with the one coated with pure MnO(2) nanofiber film.
      Therefore, the DMMP sensor developed with this composite nanostructured material
      should possess excellent selectivity and reasonable sensitivity towards the tiny
      gaseous DMMP species.

PMID- 22163654
TI  - A flexible strain sensor based on a Conductive Polymer Composite for in situ
      measurement of parachute canopy deformation.
AB  - A sensor based on a Conductive Polymer Composite (CPC), fully compatible with a
      textile substrate and its general properties, has been developed in our
      laboratory, and its electromechanical characterization is presented herein. In
      particular the effects of strain rate (from 10 to 1,000 mm/min) and of repeated
      elongation cycles on the sensor behaviour are investigated. The results show that
      strain rate seems to have little influence on sensor response. When submitted to
      repeated tensile cycles, the CPC sensor is able to detect accurately fabric
      deformations over each whole cycle, taking into account the mechanical behaviour
      of the textile substrate. Complementary information is given concerning the non
      effect of aging on the global resistivity of the CPC sensor. Finally, our sensor
      was tested on a parachute canopy during a real drop test: the canopy fabric
      deformation during the critical inflation phase was successfully measured, and
      was found to be less than 9%.

PMID- 22163655
TI  - Modeling and experimental study on characterization of micromachined thermal gas
      inertial sensors.
AB  - Micromachined thermal gas inertial sensors based on heat convection are novel
      devices that compared with conventional micromachined inertial sensors offer the
      advantages of simple structures, easy fabrication, high shock resistance and good
      reliability by virtue of using a gaseous medium instead of a mechanical proof
      mass as key moving and sensing elements. This paper presents an analytical
      modeling for a micromachined thermal gas gyroscope integrated with signal
      conditioning. A simplified spring-damping model is utilized to characterize the
      behavior of the sensor. The model relies on the use of the fluid mechanics and
      heat transfer fundamentals and is validated using experimental data obtained from
      a test-device and simulation. Furthermore, the nonideal issues of the sensor are
      addressed from both the theoretical and experimental points of view. The
      nonlinear behavior demonstrated in experimental measurements is analyzed based on
      the model. It is concluded that the sources of nonlinearity are mainly
      attributable to the variable stiffness of the sensor system and the structural
      asymmetry due to nonideal fabrication.

PMID- 22163656
TI  - FPGA-based fused smart sensor for real-time plant-transpiration dynamic
      estimation.
AB  - Plant transpiration is considered one of the most important physiological
      functions because it constitutes the plants evolving adaptation to exchange
      moisture with a dry atmosphere which can dehydrate or eventually kill the plant.
      Due to the importance of transpiration, accurate measurement methods are
      required; therefore, a smart sensor that fuses five primary sensors is proposed
      which can measure air temperature, leaf temperature, air relative humidity, plant
      out relative humidity and ambient light. A field programmable gate array based
      unit is used to perform signal processing algorithms as average decimation and
      infinite impulse response filters to the primary sensor readings in order to
      reduce the signal noise and improve its quality. Once the primary sensor readings
      are filtered, transpiration dynamics such as: transpiration, stomatal
      conductance, leaf-air-temperature-difference and vapor pressure deficit are
      calculated in real time by the smart sensor. This permits the user to observe
      different primary and calculated measurements at the same time and the
      relationship between these which is very useful in precision agriculture in the
      detection of abnormal conditions. Finally, transpiration related stress
      conditions can be detected in real time because of the use of online processing
      and embedded communications capabilities.

PMID- 22163657
TI  - Sturdy positioning with high sensitivity GPS sensors under adverse conditions.
AB  - High sensitivity GPS receivers have extended the use of GNSS navigation to
      environments which were previously deemed unsuitable for satellite signal
      reception. Under adverse conditions the signals become attenuated and reflected.
      High sensitivity receivers achieve signal reception by using a large number of
      correlators and an extended integration time. Processing the observation data in
      dynamic and rapidly changing conditions requires a careful and consistent
      treatment. Code-based autonomous solutions can cause major errors in the
      estimated position, due primarily to multipath effects. A custom procedure of
      autonomous GPS positioning has been developed, boosting the positioning
      performance through appropriate processing of code and Doppler observations.
      Besides the common positioning procedures, robust estimation methods have been
      used to minimise the effects of gross observation errors. In normal conditions,
      differential GNSS yields good results, however, under adverse conditions, it
      fails to improve significantly the receiver's position. Therefore, a so-called
      conditional DGPS has been developed which determines the position differentially
      by using data from the strong signals only. These custom-developed procedures
      have been tested in different conditions in static and kinematic cases and the
      results have been compared to those processed by the receiver.

PMID- 22163658
TI  - Minimum expected delay-based routing protocol (MEDR) for Delay Tolerant Mobile
      Sensor Networks.
AB  - It is a challenging work to develop efficient routing protocols for Delay
      Tolerant Mobile Sensor Networks (DTMSNs), which have several unique
      characteristics such as sensor mobility, intermittent connectivity, energy limit,
      and delay tolerability. In this paper, we propose a new routing protocol called
      Minimum Expected Delay-based Routing (MEDR) tailored for DTMSNs. MEDR achieves a
      good routing performance by finding and using the connected paths formed
      dynamically by mobile sensors. In MEDR, each sensor maintains two important
      parameters: Minimum Expected Delay (MED) and its expiration time. According to
      MED, messages will be delivered to the sensor that has at least a connected path
      with their hosting nodes, and has the shortest expected delay to communication
      directly with the sink node. Because of the changing network topology, the path
      is fragile and volatile, so we use the expiration time of MED to indicate the
      valid time of the path, and avoid wrong transmissions. Simulation results show
      that the proposed MEDR achieves a higher message delivery ratio with lower
      transmission overhead and data delivery delay than other DTMSN routing
      approaches.

PMID- 22163659
TI  - Color regeneration from reflective color sensor using an artificial intelligent
      technique.
AB  - A low-cost optical sensor based on reflective color sensing is presented.
      Artificial neural network models are used to improve the color regeneration from
      the sensor signals. Analog voltages of the sensor are successfully converted to
      RGB colors. The artificial intelligent models presented in this work enable color
      regeneration from analog outputs of the color sensor. Besides, inverse modeling
      supported by an intelligent technique enables the sensor probe for use of a
      colorimetric sensor that relates color changes to analog voltages.

PMID- 22163660
TI  - Data collection framework for energy efficient privacy preservation in wireless
      sensor networks having many-to-many structures.
AB  - Wireless sensor networks (WSNs) generally have a many-to-one structure so that
      event information flows from sensors to a unique sink. In recent WSN
      applications, many-to-many structures evolved due to the need for conveying
      collected event information to multiple sinks. Privacy preserved data collection
      models in the literature do not solve the problems of WSN applications in which
      network has multiple un-trusted sinks with different level of privacy
      requirements. This study proposes a data collection framework bases on k
      anonymity for preventing record disclosure of collected event information in
      WSNs. Proposed method takes the anonymity requirements of multiple sinks into
      consideration by providing different levels of privacy for each destination sink.
      Attributes, which may identify an event owner, are generalized or encrypted in
      order to meet the different anonymity requirements of sinks at the same
      anonymized output. If the same output is formed, it can be multicasted to all
      sinks. The other trivial solution is to produce different anonymized outputs for
      each sink and send them to related sinks. Multicasting is an energy efficient
      data sending alternative for some sensor nodes. Since minimization of energy
      consumption is an important design criteria for WSNs, multicasting the same event
      information to multiple sinks reduces the energy consumption of overall network.

PMID- 22163661
TI  - A novel electrochemical sensor for probing doxepin created on a glassy carbon
      electrode modified with poly(4-amino- benzoic acid)/multi-walled carbon nanotubes
      composite film.
AB  - A novel electrochemical sensor for sensitive detection of doxepin was prepared,
      which was based on a glassy carbon electrode modified with poly(4-aminobenzoic
      acid)/multi-walled carbon nanotubes composite film [poly(4-ABA)/MWNTs/GCE]. The
      sensor was characterized by scanning electron microscopy and electrochemical
      methods. It was observed that poly(4-ABA)/MWNTs/GCE showed excellent
      preconcentration function and electrocatalytic activities towards doxepin. Under
      the selected conditions, the anodic peak current was linear to the logarithm of
      doxepin concentration in the range from 1.0 * 10(-9) to 1.0 * 10(-6) M, and the
      detection limit obtained was 1.0 * 10(-10) M. The poly(4-ABA)/MWNTs/GCE was
      successfully applied in the measurement of doxepin in commercial pharmaceutical
      formulations, and the analytical accuracy was confirmed by comparison with a
      conventional ultraviolet spectrophotometry assay.

PMID- 22163662
TI  - Novel ultra-sensitive detectors in the 10-50 MUm wavelength range.
AB  - We have developed novel single-photon detectors in the 10-50 MUm wavelength
      region. The detectors are charge-sensitive infrared phototransistors (CSIPs)
      fabricated in GaAs/AlGaAs double quantum well (QW) structures, in which a photo
      generated hole (+e) in the floating gate (upper QW) modulates the conductance of
      a capacitively-coupled channel located underneath (lower QW). The excellent noise
      equivalent power (NEP = 8.3 * 10(-19) W/Hz(1/2)) and specific detectivity (D(*) =
      8 * 10(14) cm Hz(1/2)/W) are demonstrated for 15 micron detection up to 23 K,
      which are by a few orders of magnitude better than those of other state-of-the
      art high-sensitivity detectors. The dynamic range exceeds 10(6) (~aW to pW) by
      repeatedly resetting the accumulated holes in the upper QW. Simple device
      structure makes the detectors feasible for array fabrication: Furthermore,
      monolithic integration with reading circuits will be possible.

PMID- 22163663
TI  - Combined simulation of a micro permanent magnetic linear contactless displacement
      sensor.
AB  - The permanent magnetic linear contactless displacement (PLCD) sensor is a new
      type of displacement sensor operating on the magnetic inductive principle. It has
      many excellent properties and has already been used for many applications. In
      this article a Micro-PLCD sensor which can be used for microelectromechanical
      system (MEMS) measurements is designed and simulated with the CST EM STUDIO((r))
      software, including building a virtual model, magnetostatic calculations, low
      frequency calculations, steady current calculations and thermal calculations. The
      influence of some important parameters such as air gap dimension, working
      frequency, coil current and eddy currents etc. is studied in depth.

PMID- 22163664
TI  - Automated three-dimensional microbial sensing and recognition using digital
      holography and statistical sampling.
AB  - We overview an approach to providing automated three-dimensional (3D) sensing and
      recognition of biological micro/nanoorganisms integrating Gabor digital
      holographic microscopy and statistical sampling methods. For 3D data acquisition
      of biological specimens, a coherent beam propagates through the specimen and its
      transversely and longitudinally magnified diffraction pattern observed by the
      microscope objective is optically recorded with an image sensor array interfaced
      with a computer. 3D visualization of the biological specimen from the magnified
      diffraction pattern is accomplished by using the computational Fresnel
      propagation algorithm. For 3D recognition of the biological specimen, a watershed
      image segmentation algorithm is applied to automatically remove the unnecessary
      background parts in the reconstructed holographic image. Statistical estimation
      and inference algorithms are developed to the automatically segmented holographic
      image. Overviews of preliminary experimental results illustrate how the
      holographic image reconstructed from the Gabor digital hologram of biological
      specimen contains important information for microbial recognition.

PMID- 22163665
TI  - A high-sensitivity hydraulic load cell for small kitchen appliances.
AB  - In this paper we present a hydraulic load cell made from hydroformed metallic
      bellows. The load cell was designed for a small kitchen appliance with the
      weighing function integrated into the composite control and protection of the
      appliance. It is a simple, low-cost solution with small dimensions and represents
      an alternative to the existing hydraulic load cells in industrial use. A good non
      linearity and a small hysteresis were achieved. The influence of temperature
      leads to an error of 7.5%, which can be compensated for by software to meet the
      requirements of the target application.

PMID- 22163666
TI  - Detection of molecular oxygen at low concentrations using quartz enhanced
      photoacoustic spectroscopy.
AB  - Molecular oxygen is detected at low concentrations using photoacoustic
      spectroscopy despite its unfavorable photoacoustic properties. The system
      consists of a seed laser diode, a tapered amplifier and a quartz tuning fork
      based spectrophone, thus employing quartz enhanced photoacoustic spectroscopy
      (QEPAS). With this system a detection limit of 13 ppm is reached with a compact
      and long term stable setup. Further improvement of the detection limit is
      possible by adding suitable gases to the sample gas that promote the
      radiationless de-excitation of the oxygen molecules.

PMID- 22163667
TI  - Adaptive control of a vibratory angle measuring gyroscope.
AB  - This paper presents an adaptive control algorithm for realizing a vibratory angle
      measuring gyroscope so that rotation angle can be directly measured without
      integration of angular rate, thus eliminating the accumulation of numerical
      integration errors. The proposed control algorithm uses a trajectory following
      approach and the reference trajectory is generated by an ideal angle measuring
      gyroscope driven by the estimate of angular rate and the auxiliary sinusoidal
      input so that the persistent excitation condition is satisfied. The developed
      control algorithm can compensate for all types of fabrication imperfections such
      as coupled damping and stiffness, and mismatched stiffness and un-equal damping
      term in an on-line fashion. The simulation results show the feasibility and
      effectiveness of the developed control algorithm that is capable of directly
      measuring rotation angle without the integration of angular rate.

PMID- 22163668
TI  - Accurate permittivity measurements for microwave imaging via ultra-wideband
      removal of spurious reflectors.
AB  - The use of microwave imaging is becoming more prevalent for detection of interior
      hidden defects in manufactured and packaged materials. In applications for
      detection of hidden moisture, microwave tomography can be used to image the
      material and then perform an inverse calculation to derive an estimate of the
      variability of the hidden material, such internal moisture, thereby alerting
      personnel to damaging levels of the hidden moisture before material degradation
      occurs. One impediment to this type of imaging occurs with nearby objects create
      strong reflections that create destructive and constructive interference, at the
      receiver, as the material is conveyed past the imaging antenna array. In an
      effort to remove the influence of the reflectors, such as metal bale ties,
      research was conducted to develop an algorithm for removal of the influence of
      the local proximity reflectors from the microwave images. This research effort
      produced a technique, based upon the use of ultra-wideband signals, for the
      removal of spurious reflections created by local proximity reflectors. This
      improvement enables accurate microwave measurements of moisture in such products
      as cotton bales, as well as other physical properties such as density or material
      composition. The proposed algorithm was shown to reduce errors by a 4:1 ratio and
      is an enabling technology for imaging applications in the presence of metal bale
      ties.

PMID- 22163669
TI  - Sensor networks in the low lands.
AB  - This paper provides an overview of scientific and industrial developments of the
      last decade in the area of sensor networks in The Netherlands (Low Lands). The
      goal is to highlight areas in which the Netherlands has made most contributions
      and is currently a dominant player in the field of sensor networks. On the one
      hand, motivations, addressed topics, and initiatives taken in this period are
      presented, while on the other hand, special emphasis is given to identifying
      current and future trends and formulating a vision for the coming five to ten
      years. The presented overview and trend analysis clearly show that Dutch research
      and industrial efforts, in line with recent worldwide developments in the field
      of sensor technology, present a clear shift from sensor node platforms, operating
      systems, communication, networking, and data management aspects of the sensor
      networks to reasoning/cognition, control, and actuation.

PMID- 22163670
TI  - FLP/FRT recombination from yeast: application of a two gene cassette scheme as an
      inducible system in plants.
AB  - Phytosensors are plants that are genetically engineered for sensing and reporting
      the presence of a specific contaminant, including agriculturally important
      biological agents. Phytosensors are constructed by transforming plants to contain
      specific biotic- or abiotic-inducible promoters fused to a reporter gene. When
      such transgenic plants encounter the target biotic or abiotic agent, the specific
      inducible promoter is triggered and subsequently drives the expression of the
      reporter gene, which produces a signal for detection. However, several systems
      lack robustness, rapid induction and promoter strength. Here, we tested the
      FLP/FRT recombination system in a construct containing a two gene cassette
      organization and examined its potential in transgenic Arabidopsis and tobacco
      plants using a beta-glucuronidase (GUS) reporter. In this model system, a heat
      shock inducible promoter was employed to control the expression of the FLP
      recombinase gene. Upon heat induction and subsequent active FLP-mediated excision
      event, the GUS gene was placed in close proximity to the 35S promoter resulting
      in an active GUS reporter expression. Our results demonstrate that the two gene
      cassette scheme of inducible FLP/FRT recombination system is functional in
      tobacco and Arabidopsis, providing additional insights into its possible
      application in phytosensing such as creating strong readout capabilities.

PMID- 22163671
TI  - Recovery of agricultural odors and odorous compounds from polyvinyl fluoride film
      bags.
AB  - Accurate sampling methods are necessary when quantifying odor and volatile
      organic compound emissions at agricultural facilities. The commonly accepted
      methodology in the U.S. has been to collect odor samples in polyvinyl fluoride
      bags (PVF, brand name Tedlar(r)) and, subsequently, analyze with human panelists
      using dynamic triangular forced-choice olfactometry. The purpose of this research
      was to simultaneously quantify and compare recoveries of odor and odorous
      compounds from both commercial and homemade PVF sampling bags. A standard gas
      mixture consisting of p-cresol (40 MUg m(-3)) and seven volatile fatty acids:
      acetic (2,311 MUg m(-3)), propionic (15,800 MUg m(-3)), isobutyric (1,686 MUg m(
      3)), butyric (1,049 MUg m(-3)), isovaleric (1,236 MUg m(-3)), valeric (643 MUg m(
      3)), and hexanoic (2,158 MUg m(-3)) was placed in the PVF bags at times of 1 h, 1
      d, 2 d, 3 d, and 7 d prior to compound and odor concentration analyses. Compound
      concentrations were quantified using sorbent tubes and gas chromatography/mass
      spectrometry. Odor concentration, intensity, and hedonic tone were measured using
      a panel of trained human subjects. Compound recoveries ranged from 2 to 40% after
      1 h and 0 to 14% after 7 d. Between 1 h and 7 d, odor concentrations increased by
      45% in commercial bags, and decreased by 39% in homemade bags. Minimal changes
      were observed in intensity and hedonic tone over the same time period. These
      results suggest that PVF bags can bias individual compound concentrations and
      odor as measured by dynamic triangular forced-choice olfactometry.

PMID- 22163672
TI  - A rigid image registration based on the nonsubsampled contourlet transform and
      genetic algorithms.
AB  - Image registration is a fundamental task used in image processing to match two or
      more images taken at different times, from different sensors or from different
      viewpoints. The objective is to find in a huge search space of geometric
      transformations, an acceptable accurate solution in a reasonable time to provide
      better registered images. Exhaustive search is computationally expensive and the
      computational cost increases exponentially with the number of transformation
      parameters and the size of the data set. In this work, we present an efficient
      image registration algorithm that uses genetic algorithms within a multi
      resolution framework based on the Non-Subsampled Contourlet Transform (NSCT). An
      adaptable genetic algorithm for registration is adopted in order to minimize the
      search space. This approach is used within a hybrid scheme applying the two
      techniques fitness sharing and elitism. Two NSCT based methods are proposed for
      registration. A comparative study is established between these methods and a
      wavelet based one. Because the NSCT is a shift-invariant multidirectional
      transform, the second method is adopted for its search speeding up property.
      Simulation results clearly show that both proposed techniques are really
      promising methods for image registration compared to the wavelet approach, while
      the second technique has led to the best performance results of all. Moreover, to
      demonstrate the effectiveness of these methods, these registration techniques
      have been successfully applied to register SPOT, IKONOS and Synthetic Aperture
      Radar (SAR) images. The algorithm has been shown to work perfectly well for multi
      temporal satellite images as well, even in the presence of noise.

PMID- 22163673
TI  - Identification of granite varieties from colour spectrum data.
AB  - The granite processing sector of the northwest of Spain handles many varieties of
      granite with specific technical and aesthetic properties that command different
      prices in the natural stone market. Hence, correct granite identification and
      classification from the outset of processing to the end-product stage optimizes
      the management and control of stocks of granite slabs and tiles and facilitates
      the operation of traceability systems. We describe a methodology for
      automatically identifying granite varieties by processing spectral information
      captured by a spectrophotometer at various stages of processing using functional
      machine learning techniques.

PMID- 22163674
TI  - Java simulations of embedded control systems.
AB  - This paper introduces a new Open Source Java library suited for the simulation of
      embedded control systems. The library is based on the ideas and architecture of
      TrueTime, a toolbox of Matlab devoted to this topic, and allows Java programmers
      to simulate the performance of control processes which run in a real time
      environment. Such simulations can improve considerably the learning and design of
      multitasking real-time systems. The choice of Java increases considerably the
      usability of our library, because many educators program already in this
      language. But also because the library can be easily used by Easy Java
      Simulations (EJS), a popular modeling and authoring tool that is increasingly
      used in the field of Control Education. EJS allows instructors, students, and
      researchers with less programming capabilities to create advanced interactive
      simulations in Java. The paper describes the ideas, implementation, and sample
      use of the new library both for pure Java programmers and for EJS users. The JTT
      library and some examples are online available on http://lab.dia.uned.es/jtt.

PMID- 22163675
TI  - ZnO-based ultraviolet photodetectors.
AB  - Ultraviolet (UV) photodetection has drawn a great deal of attention in recent
      years due to a wide range of civil and military applications. Because of its wide
      band gap, low cost, strong radiation hardness and high chemical stability, ZnO
      are regarded as one of the most promising candidates for UV photodetectors.
      Additionally, doping in ZnO with Mg elements can adjust the bandgap largely and
      make it feasible to prepare UV photodetectors with different cut-off wavelengths.
      ZnO-based photoconductors, Schottky photodiodes, metal-semiconductor-metal
      photodiodes and p-n junction photodetectors have been developed. In this work, it
      mainly focuses on the ZnO and ZnMgO films photodetectors. We analyze the
      performance of ZnO-based photodetectors, discussing recent achievements, and
      comparing the characteristics of the various photodetector structures developed
      to date.

PMID- 22163676
TI  - Raman microspectroscopy of individual algal cells: sensing unsaturation of
      storage lipids in vivo.
AB  - Algae are becoming a strategic source of fuels, food, feedstocks, and
      biologically active compounds. This potential has stimulated the development of
      innovative analytical methods focused on these microorganisms. Algal lipids are
      among the most promising potential products for fuels as well as for nutrition.
      The crucial parameter characterizing the algal lipids is the degree of
      unsaturation of the constituent fatty acids quantified by the iodine value. Here
      we demonstrate the capacity of the spatially resolved Raman microspectroscopy to
      determine the effective iodine value in lipid storage bodies of individual living
      algal cells. The Raman spectra were collected from three selected algal species
      immobilized in an agarose gel. Prior to immobilization, the algae were cultivated
      in the stationary phase inducing an overproduction of lipids. We employed the
      characteristic peaks in the Raman scattering spectra at 1,656 cm(-1) (cis C?C
      stretching mode) and 1,445 cm(-1) (CH(2) scissoring mode) as the markers defining
      the ratio of unsaturated-to-saturated carbon-carbon bonds of the fatty acids in
      the algal lipids. These spectral features were first quantified for pure fatty
      acids of known iodine value. The resultant calibration curve was then used to
      calculate the effective iodine value of storage lipids in the living algal cells
      from their Raman spectra. We demonstrated that the iodine value differs
      significantly for the three studied algal species. Our spectroscopic estimations
      of the iodine value were validated using GC-MS measurements and an excellent
      agreement was found for the Trachydiscus minutus species. A good agreement was
      also found with the earlier published data on Botryococcus braunii. Thus, we
      propose that Raman microspectroscopy can become technique of choice in the
      rapidly expanding field of algal biotechnology.

PMID- 22163677
TI  - Predicting the detectability of thin gaseous plumes in hyperspectral images using
      basis vectors.
AB  - This paper describes a new method for predicting the detectability of thin
      gaseous plumes in hyperspectral images. The novelty of this method is the use of
      basis vectors for each of the spectral channels of a collection instrument to
      calculate noise-equivalent concentration-pathlengths instead of matching scene
      pixels to absorbance spectra of gases in a library. This method provides insight
      into regions of the spectrum where gas detection will be relatively easier or
      harder, as influenced by ground emissivity, temperature contrast, and the
      atmosphere. Our results show that data collection planning could be influenced by
      information about when potential plumes are likely to be over background segments
      that are most conducive to detection.

PMID- 22163678
TI  - Automated construction of node software using attributes in a ubiquitous sensor
      network environment.
AB  - In sensor networks, nodes must often operate in a demanding environment facing
      restrictions such as restricted computing resources, unreliable wireless
      communication and power shortages. Such factors make the development of
      ubiquitous sensor network (USN) applications challenging. To help developers
      construct a large amount of node software for sensor network applications easily
      and rapidly, this paper proposes an approach to the automated construction of
      node software for USN applications using attributes. In the proposed technique,
      application construction proceeds by first developing a model for the sensor
      network and then designing node software by setting the values of the predefined
      attributes. After that, the sensor network model and the design of node software
      are verified. The final source codes of the node software are automatically
      generated from the sensor network model. We illustrate the efficiency of the
      proposed technique by using a gas/light monitoring application through a case
      study of a Gas and Light Monitoring System based on the Nano-Qplus operating
      system. We evaluate the technique using a quantitative metric-the memory size of
      execution code for node software. Using the proposed approach, developers are
      able to easily construct sensor network applications and rapidly generate a large
      number of node softwares at a time in a ubiquitous sensor network environment.

PMID- 22163679
TI  - Broadcast authentication for wireless sensor networks using nested hashing and
      the Chinese remainder theorem.
AB  - Secure broadcasting is an essential feature for critical operations in wireless
      sensor network (WSNs). However, due to the limited resources of sensor networks,
      verifying the authenticity for broadcasted messages is a very difficult issue.
      MUTESLA is a broadcast authentication protocol, which uses network-wide loose
      time synchronization with one-way hashed keys to provide the authenticity
      verification. However, it suffers from several flaws considering the delay
      tolerance, and the chain length restriction. In this paper, we propose a protocol
      which provides broadcast authentication for wireless sensor networks. This
      protocol uses a nested hash chain of two different hash functions and the Chinese
      Remainder Theorem (CRT). The two different nested hash functions are employed for
      the seed updating and the key generation. Each sensor node is challenged
      independently with a common broadcasting message using the CRT. Our algorithm
      provides forward and non-restricted key generation, and in addition, no time
      synchronization is required. Furthermore, receivers can instantly authenticate
      packets in real time. Moreover, the comprehensive analysis shows that this scheme
      is efficient and practical, and can achieve better performance than the MUTESLA
      system.

PMID- 22163680
TI  - Inverse problem in nondestructive testing using arrayed eddy current sensors.
AB  - A fast crack profile reconstitution model in nondestructive testing is developed
      using an arrayed eddy current sensor. The inverse problem is based on an
      iterative solving of the direct problem using genetic algorithms. In the direct
      problem, assuming a current excitation, the incident field produced by all the
      coils of the arrayed sensor is obtained by the translation and superposition of
      the 2D axisymmetric finite element results obtained for one coil; the impedance
      variation of each coil, due to the crack, is obtained by the reciprocity
      principle involving the dyadic Green's function. For the inverse problem, the
      surface of the crack is subdivided into rectangular cells, and the objective
      function is expressed only in terms of the depth of each cell. The evaluation of
      the dyadic Green's function matrix is made independently of the iterative
      procedure, making the inversion very fast.

PMID- 22163681
TI  - Assessment of human ambulatory speed by measuring near-body air flow.
AB  - Accurate measurements of physical activity are important for the diagnosis of the
      exacerbation of chronic diseases. Accelerometers have been widely employed in
      clinical research for measuring activity intensity and investigating the
      association between physical activity and adverse health conditions. However, the
      ability of accelerometers in assessing physical activity intensity such as
      walking speed has been constrained by the inter-individual variability in sensor
      output and by the necessity of developing unobtrusive low-power monitoring
      systems. This paper will present a study aimed at investigating the accuracy of a
      wearable measuring system of near-body air flow to determine ambulatory speed in
      the field.

PMID- 22163682
TI  - A signal normalization technique for illumination-based synchronization of 1,000
      fps real-time vision sensors in dynamic scenes.
AB  - To acquire images of dynamic scenes from multiple points of view simultaneously,
      the acquisition time of vision sensors should be synchronized. In this paper, an
      illumination-based synchronization derived from the phase-locked loop (PLL)
      mechanism based on the signal normalization method is proposed and evaluated. To
      eliminate the system dependency due to the amplitude fluctuation of the reference
      illumination, which may be caused by the moving objects or relative positional
      distance change between the light source and the observed objects, the fluctuant
      amplitude of the reference signal is normalized framely by the estimated maximum
      amplitude between the reference signal and its quadrature counterpart to generate
      a stable synchronization in highly dynamic scenes. Both simulated results and
      real world experimental results demonstrated successful synchronization result
      that 1,000-Hz frame rate vision sensors can be successfully synchronized to a LED
      illumination or its reflected light with satisfactory stability and only 28-MUs
      jitters.

PMID- 22163683
TI  - Design and analysis of MEMS based PVDF ultrasonic transducers for vascular
      imaging.
AB  - Polyvinilidene fluoride (PVDF) single-element transducers for high-frequency (>30
      MHz) ultrasound imaging applications have been developed using MEMS (Micro
      electro-Mechanical Systems) compatible techniques. Performance of these
      transducers has been investigated by analyzing the sources and effects of on-chip
      parasitic capacitances on the insertion-loss of the transducers. Modeling and
      experimental studies showed that on-chip parasitic capacitances degraded the
      performance of the transducers and an improved method of fabrication was
      suggested and new devices were built. New devices developed with minimal
      parasitic effects were shown to improve the performance significantly. A 1-mm
      aperture PVDF device developed with minimal parasitic effects has resulted in a
      reduction of insertion loss of 21 dB compared with devices fabricated using a
      previous method.

PMID- 22163684
TI  - Characteristics of metal enhanced evanescent-wave microcavities.
AB  - This article presents the concept of storing optical energy using a metallic air
      gap microcavity. Evanescent waves are stored in the air gap of a
      dielectric/metal/air gap/metal planar microcavity. For an air gap with a micron
      scale distance between the two metals, incident light excites the optical
      interface modes on the two metal-air interfaces simultaneously, being accompanied
      by enhanced evanescent fields. Numerical simulations show that the reflected
      light depends remarkably upon distributions of the enhanced electric fields in
      the air-gap at the optical mode excitations. The metallic microcavities have a Q
      value on the order of 10(2), as determined from calculations. Experimentally, a
      small mechanical variation of the air-gap distance exhibited a change of
      reflectivity.

PMID- 22163685
TI  - Load-adaptive practical multi-channel communications in wireless sensor networks.
AB  - In recent years, a significant number of sensor node prototypes have been
      designed that provide communications in multiple channels. This multi-channel
      feature can be effectively exploited to increase the overall capacity and
      performance of wireless sensor networks (WSNs). In this paper, we present a multi
      channel communications system for WSNs that is referred to as load-adaptive
      practical multi-channel communications (LPMC). LPMC estimates the active load of
      a channel at the sink since it has a more comprehensive view of the network
      behavior, and dynamically adds or removes channels based on the estimated load.
      LPMC updates the routing path to balance the loads of the channels. The nodes in
      a path use the same channel; therefore, they do not need to switch channels to
      receive or forward packets. LPMC has been evaluated through extensive
      simulations, and the results demonstrate that it can effectively increase the
      delivery ratio, network throughput, and channel utilization, and that it can
      decrease the end-to-end delay and energy consumption.

PMID- 22163686
TI  - A novel approach for foreign substances detection in injection using clustering
      and frame difference.
AB  - This paper focuses on developing a novel technique based on machine vision for
      detection of foreign substances in injections. Mechanical control yields
      spin/stop movement of injections which helps to cause relative movement between
      foreign substances in liquid and an ampoule bottle. Foreign substances are
      classified into two categories: subsiding-slowly object and subsiding-fast
      object. A sequence of frames are captured by a camera and used to recognize
      foreign substances. After image preprocessing like noise reduction and motion
      detection, two different methods, Moving-object Clustering (MC) and Frame
      Difference, are proposed to detect the two categories respectively. MC is
      operated to cluster subsiding-slowly foreign substances, based on the invariant
      features of those objects. Frame Difference is defined to calculate the
      difference between two frames due to the change of subsiding-fast objects. 200
      ampoule samples filled with injection are tested and the experimental result
      indicates that the approach can detect the visible foreign substances
      effectively.

PMID- 22163687
TI  - An architecture for performance optimization in a collaborative knowledge-based
      approach for wireless sensor networks.
AB  - Over the past few years, Intelligent Spaces (ISs) have received the attention of
      many Wireless Sensor Network researchers. Recently, several studies have been
      devoted to identify their common capacities and to set up ISs over these
      networks. However, little attention has been paid to integrating Fuzzy Rule-Based
      Systems into collaborative Wireless Sensor Networks for the purpose of
      implementing ISs. This work presents a distributed architecture proposal for
      collaborative Fuzzy Rule-Based Systems embedded in Wireless Sensor Networks,
      which has been designed to optimize the implementation of ISs. This architecture
      includes the following: (a) an optimized design for the inference engine; (b) a
      visual interface; (c) a module to reduce the redundancy and complexity of the
      knowledge bases; (d) a module to evaluate the accuracy of the new knowledge base;
      (e) a module to adapt the format of the rules to the structure used by the
      inference engine; and (f) a communications protocol. As a real-world application
      of this architecture and the proposed methodologies, we show an application to
      the problem of modeling two plagues of the olive tree: prays (olive moth, Prays
      oleae Bern.) and repilo (caused by the fungus Spilocaea oleagina). The results
      show that the architecture presented in this paper significantly decreases the
      consumption of resources (memory, CPU and battery) without a substantial decrease
      in the accuracy of the inferred values.

PMID- 22163688
TI  - Efficient phase unwrapping architecture for digital holographic microscopy.
AB  - This paper presents a novel phase unwrapping architecture for accelerating the
      computational speed of digital holographic microscopy (DHM). A fast Fourier
      transform (FFT) based phase unwrapping algorithm providing a minimum squared
      error solution is adopted for hardware implementation because of its simplicity
      and robustness to noise. The proposed architecture is realized in a pipeline
      fashion to maximize throughput of the computation. Moreover, the number of
      hardware multipliers and dividers are minimized to reduce the hardware costs. The
      proposed architecture is used as a custom user logic in a system on programmable
      chip (SOPC) for physical performance measurement. Experimental results reveal
      that the proposed architecture is effective for expediting the computational
      speed while consuming low hardware resources for designing an embedded DHM
      system.

PMID- 22163689
TI  - Kalman-filter-based orientation determination using inertial/magnetic sensors:
      observability analysis and performance evaluation.
AB  - In this paper we present a quaternion-based Extended Kalman Filter (EKF) for
      estimating the three-dimensional orientation of a rigid body. The EKF exploits
      the measurements from an Inertial Measurement Unit (IMU) that is integrated with
      a tri-axial magnetic sensor. Magnetic disturbances and gyro bias errors are
      modeled and compensated by including them in the filter state vector. We employ
      the observability rank criterion based on Lie derivatives to verify the
      conditions under which the nonlinear system that describes the process of motion
      tracking by the IMU is observable, namely it may provide sufficient information
      for performing the estimation task with bounded estimation errors. The
      observability conditions are that the magnetic field, perturbed by first-order
      Gauss-Markov magnetic variations, and the gravity vector are not collinear and
      that the IMU is subject to some angular motions. Computer simulations and
      experimental testing are presented to evaluate the algorithm performance,
      including when the observability conditions are critical.

PMID- 22163691
TI  - Genetic algorithm for the design of electro-mechanical sigma delta modulator MEMS
      sensors.
AB  - This paper describes a novel design methodology using non-linear models for
      complex closed loop electro-mechanical sigma-delta modulators (EMSigmaDeltaM)
      that is based on genetic algorithms and statistical variation analysis. The
      proposed methodology is capable of quickly and efficiently designing high
      performance, high order, closed loop, near-optimal systems that are robust to
      sensor fabrication tolerances and electronic component variation. The use of full
      non-linear system models allows significant higher order non-ideal effects to be
      taken into account, improving accuracy and confidence in the results. To
      demonstrate the effectiveness of the approach, two design examples are presented
      including a 5th order low-pass EMSigmaDeltaM for a MEMS accelerometer, and a 6th
      order band-pass EMSigmaDeltaM for the sense mode of a MEMS gyroscope. Each
      example was designed using the system in less than one day, with very little
      manual intervention. The strength of the approach is verified by SNR performances
      of 109.2 dB and 92.4 dB for the low-pass and band-pass system respectively,
      coupled with excellent immunities to fabrication tolerances and parameter
      mismatch.

PMID- 22163690
TI  - Synthesis of nanocrystalline SnO(x) (x = 1-2) thin film using a chemical bath
      deposition method with improved deposition time, temperature and pH.
AB  - Nanocrystalline SnO(x) (x = 1-2) thin films were prepared on glass substrates by
      a simple chemical bath deposition method. Triethanolamine was used as complexing
      agent to decrease time and temperature of deposition and shift the pH of the
      solution to the noncorrosive region. The films were characterized for
      composition, surface morphology, structure and optical properties. X-ray
      diffraction analysis confirms that SnO(x) thin films consist of a polycrystalline
      structure with an average grain size of 36 nm. Atomic force microscopy studies
      show a uniform grain distribution without pinholes. The elemental composition was
      evaluated by energy dispersive X-ray spectroscopy. The average O/Sn atomic
      percentage ratio is 1.72. Band gap energy and optical transition were determined
      from optical absorbance data. The film was found to exhibit direct and indirect
      transitions in the visible spectrum with band gap values of about 3.9 and 3.7 eV,
      respectively. The optical transmittance in the visible region is 82%. The SnO(x)
      nanocrystals exhibit an ultraviolet emission band centered at 392 nm in the
      vicinity of the band edge, which is attributed to the well-known exciton
      transition in SnO(x). Photosensitivity was detected in the positive region under
      illumination with white light.

PMID- 22163692
TI  - A comparison of delayed self-heterodyne interference measurement of laser
      linewidth using Mach-Zehnder and Michelson interferometers.
AB  - Linewidth measurements of a distributed feedback (DFB) fibre laser are made using
      delayed self heterodyne interferometry (DHSI) with both Mach-Zehnder and
      Michelson interferometer configurations. Voigt fitting is used to extract and
      compare the Lorentzian and Gaussian linewidths and associated sources of noise.
      The respective measurements are w(L) (MZI) = (1.6 +/- 0.2) kHz and w(L) (MI) =
      (1.4 +/- 0.1) kHz. The Michelson with Faraday rotator mirrors gives a slightly
      narrower linewidth with significantly reduced error. This is explained by the
      unscrambling of polarisation drift using the Faraday rotator mirrors, confirmed
      by comparing with non-rotating standard gold coated fibre end mirrors.

PMID- 22163693
TI  - Design of a covert RFID tag network for target discovery and target information
      routing.
AB  - Radio frequency identification (RFID) tags are small electronic devices working
      in the radio frequency range. They use wireless radio communications to
      automatically identify objects or people without the need for line-of-sight or
      contact, and are widely used in inventory tracking, object location,
      environmental monitoring. This paper presents a design of a covert RFID tag
      network for target discovery and target information routing. In the design, a
      static or very slowly moving target in the field of RFID tags transmits a
      distinct pseudo-noise signal, and the RFID tags in the network collect the target
      information and route it to the command center. A map of each RFID tag's location
      is saved at command center, which can determine where a RFID tag is located based
      on each RFID tag's ID. We propose the target information collection method with
      target association and clustering, and we also propose the information routing
      algorithm within the RFID tag network. The design and operation of the proposed
      algorithms are illustrated through examples. Simulation results demonstrate the
      effectiveness of the design.

PMID- 22163694
TI  - Analysis of deflection enhancement using epsilon assembly microcantilevers based
      sensors.
AB  - The present work analyzes theoretically and verifies the advantage of utilizing E
      microcantilever assemblies in microsensing applications. The deflection profile
      of these innovative E-assembly microcantilevers is compared with that of the
      rectangular microcantilever and modified triangular microcantlever. Various force
      loading conditions are considered. The theorem of linear elasticity for thin
      beams is used to obtain the deflections. The obtained defections are validated
      against an accurate numerical solution utilizing finite element method with
      maximum deviation less than 10 percent. It is found that the E-assembly produces
      larger deflections than the rectangular microcantilever under the same base
      surface stress and same extension length. In addition, the E-microcantilever
      assembly is found to produce larger deflection than the modified triangular
      microcantilever. This deflection enhancement is found to increase as the E
      assembly's free length decreases for various types of force loading conditions.
      Consequently, the E-microcantilever is shown to be superior in microsensing
      applications as it provides favorable high detection capability with a reduced
      susceptibility to external noises. Finally, this work paves a way for
      experimentally testing the E-assembly to show whether detective potential of
      microsensors can be increased.

PMID- 22163695
TI  - The potential for harvesting energy from the movement of trees.
AB  - Over the last decade, wireless devices have decreased in size and power
      requirements. These devices generally use batteries as a power source but can
      employ additional means of power, such as solar, thermal or wind energy. However,
      sensor networks are often deployed in conditions of minimal lighting and thermal
      gradient such as densely wooded environments, where even normal wind energy
      harvesting is limited. In these cases a possible source of energy is from the
      motion of the trees themselves. We investigated the amount of energy and power
      available from the motion of a tree in a sheltered position, during Beaufort 4
      winds. We measured the work performed by the tree to lift a mass, we measured
      horizontal acceleration of free movement, and we determined the angular
      deflection of the movement of the tree trunk, to determine the energy and power
      available to various types of harvesting devices. We found that the amount of
      power available from the tree, as demonstrated by lifting a mass, compares
      favourably with the power required to run a wireless sensor node.

PMID- 22163696
TI  - A conductometric indium oxide semiconducting nanoparticle enzymatic biosensor
      array.
AB  - We report a conductometric nanoparticle biosensor array to address the
      significant variation of electrical property in nanomaterial biosensors due to
      the random network nature of nanoparticle thin-film. Indium oxide and silica
      nanoparticles (SNP) are assembled selectively on the multi-site channel area of
      the resistors using layer-by-layer self-assembly. To demonstrate enzymatic
      biosensing capability, glucose oxidase is immobilized on the SNP layer for
      glucose detection. The packaged sensor chip onto a ceramic pin grid array is
      tested using syringe pump driven feed and multi-channel I-V measurement system.
      It is successfully demonstrated that glucose is detected in many different
      sensing sites within a chip, leading to concentration dependent currents. The
      sensitivity has been found to be dependent on the channel length of the resistor,
      4-12 nA/mM for channel lengths of 5-20 MUm, while the apparent Michaelis-Menten
      constant is 20 mM. By using sensor array, analytical data could be obtained with
      a single step of sample solution feeding. This work sheds light on the
      applicability of the developed nanoparticle microsensor array to multi-analyte
      sensors, novel bioassay platforms, and sensing components in a lab-on-a-chip.

PMID- 22163697
TI  - Hall-effect based semi-fast AC on-board charging equipment for electric vehicles.
AB  - The expected increase in the penetration of electric vehicles (EV) and plug-in
      hybrid electric vehicles (PHEV) will produce unbalanced conditions, reactive
      power consumption and current harmonics drawn by the battery charging equipment,
      causing a great impact on the power quality of the future smart grid. A single
      phase semi-fast electric vehicle battery charger is proposed in this paper. This
      ac on-board charging equipment can operate in grid-to-vehicle (G2V) mode, and
      also in vehicle-to-grid (V2G) mode, transferring the battery energy to the grid
      when the vehicle is parked. The charger is controlled with a Perfect Harmonic
      Cancellation (PHC) strategy, contributing to improve the grid power quality,
      since the current demanded or injected has no harmonic content and a high power
      factor. Hall-effect current and voltage transducers have been used in the sensor
      stage to carry out this control strategy. Experimental results with a laboratory
      prototype are presented.

PMID- 22163698
TI  - A game theory-based obstacle avoidance routing protocol for wireless sensor
      networks.
AB  - The obstacle avoidance problem in geographic forwarding is an important issue for
      location-based routing in wireless sensor networks. The presence of an obstacle
      leads to several geographic routing problems such as excessive energy consumption
      and data congestion. Obstacles are hard to avoid in realistic environments. To
      bypass obstacles, most routing protocols tend to forward packets along the
      obstacle boundaries. This leads to a situation where the nodes at the boundaries
      exhaust their energy rapidly and the obstacle area is diffused. In this paper, we
      introduce a novel routing algorithm to solve the obstacle problem in wireless
      sensor networks based on a game-theory model. Our algorithm forms a concave
      region that cannot forward packets to achieve the aim of improving the
      transmission success rate and decreasing packet transmission delays. We consider
      the residual energy, out-degree and forwarding angle to determine the forwarding
      probability and payoff function of forwarding candidates. This achieves the aim
      of load balance and reduces network energy consumption. Simulation results show
      that based on the average delivery delay, energy consumption and packet delivery
      ratio performances our protocol is superior to other traditional schemes.

PMID- 22163699
TI  - Determination of ammonium ion using a reagentless amperometric biosensor based on
      immobilized alanine dehydrogenase.
AB  - The use of the enzyme alanine dehydrogenase (AlaDH) for the determination of
      ammonium ion (NH(4)(+)) usually requires the addition of pyruvate substrate and
      reduced nicotinamide adenine dinucleotide (NADH) simultaneously to effect the
      reaction. This addition of reagents is inconvenient when an enzyme biosensor
      based on AlaDH is used. To resolve the problem, a novel reagentless amperometric
      biosensor using a stacked methacrylic membrane system coated onto a screen
      printed carbon paste electrode (SPE) for NH(4)(+) ion determination is described.
      A mixture of pyruvate and NADH was immobilized in low molecular weight poly(2
      hydroxyethyl methacrylate) (pHEMA) membrane, which was then deposited over a
      photocured pHEMA membrane (photoHEMA) containing alanine dehydrogenase (AlaDH)
      enzyme. Due to the enzymatic reaction of AlaDH and the pyruvate substrate,
      NH(4)(+) was consumed in the process and thus the signal from the
      electrocatalytic oxidation of NADH at an applied potential of +0.55 V was
      proportional to the NH(4)(+) ion concentration under optimal conditions. The
      stacked methacrylate membranes responded rapidly and linearly to changes in
      NH(4)(+) ion concentrations between 10-100 mM, with a detection limit of 0.18 mM
      NH(4)(+) ion. The reproducibility of the amperometrical NH(4)(+) biosensor
      yielded low relative standard deviations between 1.4-4.9%. The stacked membrane
      biosensor has been successfully applied to the determination of NH(4)(+) ion in
      spiked river water samples without pretreatment. A good correlation was found
      between the analytical results for NH(4)(+) obtained from the biosensor and the
      Nessler spectrophotometric method.

PMID- 22163700
TI  - UniDA: uniform device access framework for human interaction environments.
AB  - Human interaction environments (HIE) must be understood as any place where people
      carry out their daily life, including their work, family life, leisure and social
      life, interacting with technology to enhance or facilitate the experience. The
      integration of technology in these environments has been achieved in a disorderly
      and incompatible way, with devices operating in isolated islands with artificial
      edges delimited by the manufacturers. In this paper we are presenting the UniDA
      framework, an integral solution for the development of systems that require the
      integration and interoperation of devices and technologies in HIEs. It provides
      developers and installers with a uniform conceptual framework capable of
      modelling an HIE, together with a set of libraries, tools and devices to build
      distributed instrumentation networks with support for transparent integration of
      other technologies. A series of use case examples and a comparison to many of the
      existing technologies in the field has been included in order to show the
      benefits of using UniDA.

PMID- 22163701
TI  - PDR with a foot-mounted IMU and ramp detection.
AB  - The localization of persons in indoor environments is nowadays an open problem.
      There are partial solutions based on the deployment of a network of sensors
      (Local Positioning Systems or LPS). Other solutions only require the installation
      of an inertial sensor on the person's body (Pedestrian Dead-Reckoning or PDR).
      PDR solutions integrate the signals coming from an Inertial Measurement Unit
      (IMU), which usually contains 3 accelerometers and 3 gyroscopes. The main problem
      of PDR is the accumulation of positioning errors due to the drift caused by the
      noise in the sensors. This paper presents a PDR solution that incorporates a
      drift correction method based on detecting the access ramps usually found in
      buildings. The ramp correction method is implemented over a PDR framework that
      uses an Inertial Navigation algorithm (INS) and an IMU attached to the person's
      foot. Unlike other approaches that use external sensors to correct the drift
      error, we only use one IMU on the foot. To detect a ramp, the slope of the
      terrain on which the user is walking, and the change in height sensed when moving
      forward, are estimated from the IMU. After detection, the ramp is checked for
      association with one of the existing in a database. For each associated ramp, a
      position correction is fed into the Kalman Filter in order to refine the INS-PDR
      solution. Drift-free localization is achieved with positioning errors below 2
      meters for 1,000-meter-long routes in a building with a few ramps.

PMID- 22163702
TI  - MC sensor--a novel method for measurement of muscle tension.
AB  - This paper presents a new muscle contraction (MC) sensor. This MC sensor is based
      on a novel principle whereby muscle tension is measured during muscle
      contractions. During the measurement, the sensor is fixed on the skin surface
      above the muscle, while the sensor tip applies pressure and causes an indentation
      of the skin and intermediate layer directly above the muscle and muscle itself.
      The force on the sensor tip is then measured. This force is roughly proportional
      to the tension of the muscle. The measurement is non-invasive and selective.
      Selectivity of MC measurement refers to the specific muscle or part of the muscle
      that is being measured and is limited by the size of the sensor tip. The sensor
      is relatively small and light so that the measurements can be performed while the
      measured subject performs different activities. Test measurements with this MC
      sensor on the biceps brachii muscle under isometric conditions (elbow angle 90
      degrees ) showed a high individual linear correlation between the isometric force
      and MC signal amplitudes (0.97 <= r <= 1). The measurements also revealed a
      strong correlation between the MC and electromyogram (EMG) signals as well as
      good dynamic behaviour by the MC sensor. We believe that this MC sensor, when
      fully tested, will be a useful device for muscle mechanic diagnostics and that it
      will be complementary to existing methods.

PMID- 22163703
TI  - Human thrombin detection through a sandwich aptamer microarray: interaction
      analysis in solution and in solid phase.
AB  - We have developed an aptamer-based microarray for human thrombin detection
      exploiting two non-overlapping DNA thrombin aptamers recognizing different
      exosites of the target protein. The 15-mer aptamer (TBA1) binds the fibrinogen
      binding site, whereas the 29-mer aptamer (TBA2) binds the heparin binding domain.
      Extensive analysis on the complex formation between human thrombin and modified
      aptamers was performed by Electrophoresis Mobility Shift Assay (EMSA), in order
      to verify in solution whether the chemical modifications introduced would affect
      aptamers/protein recognition. The validated system was then applied to the
      aptamer microarray, using the solid phase system devised by the solution studies.
      Finally, the best procedure for Sandwich Aptamer Microarray (SAM) and the
      specificity of the sandwich formation for the developed aptasensor for human
      thrombin were optimized.

PMID- 22163704
TI  - Self-assembled films of dendrimers and metallophthalocyanines as FET-based
      glucose biosensors.
AB  - Separative extended gate field effect transistor (SEGFET) type devices have been
      used as an ion sensor or biosensor as an alternative to traditional ion sensitive
      field effect transistors (ISFETs) due to their robustness, ease of fabrication,
      low cost and possibility of FET isolation from the chemical environment. The
      layer-by-layer technique allows the combination of different materials with
      suitable properties for enzyme immobilization on simple platforms such as the
      extended gate of SEGFET devices enabling the fabrication of biosensors. Here,
      glucose biosensors based on dendrimers and metallophthalocyanines (MPcs) in the
      form of layer-by-layer (LbL) films, assembled on indium tin oxide (ITO) as
      separative extended gate material, has been produced. NH(3)(+) groups in the
      dendrimer allow electrostatic interactions or covalent bonds with the enzyme
      (glucose oxidase). Relevant parameters such as optimum pH, buffer concentration
      and presence of serum bovine albumin (BSA) in the immobilization process were
      analyzed. The relationship between the output voltage and glucose concentration
      shows that upon detection of a specific analyte, the sub-products of the
      enzymatic reaction change the pH locally, affecting the output signal of the FET
      transducer. In addition, dendritic layers offer a nanoporous environment, which
      may be permeable to H(+) ions, improving the sensibility as modified electrodes
      for glucose biosensing.

PMID- 22163705
TI  - Biosensor applications in the field of antibiotic research--a review of recent
      developments.
AB  - Antibacterials are among of the most important medications used in health care.
      However, their efficacy is increasingly impeded by a tremendous and globally
      spread bacterial resistance phenomenon. This bacterial resistance is accelerated
      by inadequate application of antibacterial drugs in humans, the widespread
      veterinary use of antibacterials, and antibacterial occurrence in the environment
      and food. Further, there is a lack of development of innovative novel drugs.
      Therefore, the search for novel antibacterials has to be intensified and the
      spread of antibacterials in the environment has to be restricted. Due to the
      fundamental progress in biosensor development and promising applications in the
      antibiotic field, this review gives for the first time an overview on the use and
      prospects of biosensor applications in that area. A number of reports have
      applied biosensors of different design and techniques to search for
      antibacterials in environmental and foodstuff matrices. These studies are
      discussed with respect to the analytical values and compared to conventional
      techniques. Furthermore, biosensor applications to elucidate the mode of action
      of antimicrobial drugs in vitro have been described. These studies were
      critically introduced referring to the informational value of those simulations.
      In summary, biosensors will be illustrated as an innovative and promising,
      although not yet comprehensively applied, technique in the antibacterial field.

PMID- 22163706
TI  - Optical sensing method for screening disease in melon seeds by using optical
      coherence tomography.
AB  - We report a noble optical sensing method to diagnose seed abnormalities using
      optical coherence tomography (OCT). Melon seeds infected with Cucumber green
      mottle mosaic virus (CGMMV) were scanned by OCT. The cross-sectional sensed area
      of the abnormal seeds showed an additional subsurface layer under the surface
      which is not found in normal seeds. The presence of CGMMV in the sample was
      examined by a blind test (n = 140) and compared by the reverse transcription
      polymerase chain reaction. The abnormal layers (n = 40) were quantitatively
      investigated using A-scan sensing analysis and statistical method. By utilizing
      3D OCT image reconstruction, we confirmed the distinctive layers on the whole
      seeds. These results show that OCT with the proposed data processing method can
      systemically pick up morphological modification induced by viral infection in
      seeds, and, furthermore, OCT can play an important role in automatic screening of
      viral infections in seeds.

PMID- 22163707
TI  - Simultaneous application of fibrous piezoresistive sensors for compression and
      traction detection in glass laminate composites.
AB  - This article describes further development of a novel Non Destructive Evaluation
      (NDE) approach described in one of our previous papers. Here these sensors have
      been used for the first time as a Piecewise Continuous System (PCS), which means
      that they are not only capable of following the deformation pattern but can also
      detect distinctive fracture events. In order to characterize the simultaneous
      compression and traction response of these sensors, multilayer glass laminate
      composite samples were prepared for 3-point bending tests. The laminate sample
      consisted of five layers of plain woven glass fabrics placed one over another.
      The sensors were placed at two strategic locations during the lay-up process so
      as to follow traction and compression separately. The reinforcements were then
      impregnated in epoxy resin and later subjected to 3-point bending tests. An
      appropriate data treatment and recording device has also been developed and used
      for simultaneous data acquisition from the two sensors. The results obtained,
      under standard testing conditions have shown that our textile fibrous sensors can
      not only be used for simultaneous detection of compression and traction in
      composite parts for on-line structural health monitoring but their sensitivity
      and carefully chosen location inside the composite ensures that each fracture
      event is indicated in real time by the output signal of the sensor.

PMID- 22163708
TI  - Performance evaluation of a biometric system based on acoustic images.
AB  - An acoustic electronic scanning array for acquiring images from a person using a
      biometric application is developed. Based on pulse-echo techniques,
      multifrequency acoustic images are obtained for a set of positions of a person
      (front, front with arms outstretched, back and side). Two Uniform Linear Arrays
      (ULA) with 15 lambda/2-equispaced sensors have been employed, using different
      spatial apertures in order to reduce sidelobe levels. Working frequencies have
      been designed on the basis of the main lobe width, the grating lobe levels and
      the frequency responses of people and sensors. For a case-study with 10 people,
      the acoustic profiles, formed by all images acquired, are evaluated and compared
      in a mean square error sense. Finally, system performance, using False Match Rate
      (FMR)/False Non-Match Rate (FNMR) parameters and the Receiver Operating
      Characteristic (ROC) curve, is evaluated. On the basis of the obtained results,
      this system could be used for biometric applications.

PMID- 22163709
TI  - A label-free electrochemical immunosensor for carbofuran detection based on a sol
      gel entrapped antibody.
AB  - In this study, an anti-carbofuran monoclonal antibody (Ab) was immobilized on the
      surface of a glassy carbon electrode (GCE) using silica sol-gel (SiSG)
      technology. Thus, a sensitive, label-free electrochemical immunosensor for the
      direct determination of carbofuran was developed. The electrochemical performance
      of immunoreaction of antigen with the anti-carbofuran monoclonal antibody was
      investigated by cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS), in which phosphate buffer solution containing [Fe(CN)(6)](3
      /4-) was used as the base solution for test. Because the complex formed by the
      immunoreaction hindered the diffusion of [Fe(CN)(6)](3-/4-) on the electrode
      surface, the redox peak current of the immunosensor in the CV obviously decreased
      with the increase of the carbofuran concentration. The pH of working solution,
      the concentration of Ab and the incubation time of carbofuran were studied to
      ensure the sensitivity and conductivity of the immunosensor. Under the optimal
      conditions, the linear range of the proposed immunosensor for the determination
      of carbofuran was from 1 ng/mL to 100 MUg/mL and from 50 MUg/mL to 200 MUg/mL
      with a detection limit of 0.33 ng/mL (S/N = 3). The proposed immunosensor
      exhibited good high sensitivity and stability, and it was thus suitable for trace
      detection of carbofuran pesticide residues.

PMID- 22163710
TI  - A new laboratory radio frequency identification (RFID) system for behavioural
      tracking of marine organisms.
AB  - Radio frequency identification (RFID) devices are currently used to quantify
      several traits of animal behaviour with potential applications for the study of
      marine organisms. To date, behavioural studies with marine organisms are rare
      because of the technical difficulty of propagating radio waves within the
      saltwater medium. We present a novel RFID tracking system to study the burrowing
      behaviour of a valuable fishery resource, the Norway lobster (Nephrops norvegicus
      L.). The system consists of a network of six controllers, each handling a group
      of seven antennas. That network was placed below a microcosm tank that recreated
      important features typical of Nephrops' grounds, such as the presence of multiple
      burrows. The animals carried a passive transponder attached to their telson,
      operating at 13.56 MHz. The tracking system was implemented to concurrently
      report the behaviour of up to three individuals, in terms of their travelled
      distances in a specified unit of time and their preferential positioning within
      the antenna network. To do so, the controllers worked in parallel to send the
      antenna data to a computer via a USB connection. The tracking accuracy of the
      system was evaluated by concurrently recording the animals' behaviour with
      automated video imaging. During the two experiments, each lasting approximately
      one week, two different groups of three animals each showed a variable burrow
      occupancy and a nocturnal displacement under a standard photoperiod regime (12 h
      light:12 h dark), measured using the RFID method. Similar results were obtained
      with the video imaging. Our implemented RFID system was therefore capable of
      efficiently tracking the tested organisms and has a good potential for use on a
      wide variety of other marine organisms of commercial, aquaculture, and ecological
      interest.

PMID- 22163711
TI  - Development of a 2-channel embedded infrared fiber-optic temperature sensor using
      silver halide optical fibers.
AB  - A 2-channel embedded infrared fiber-optic temperature sensor was fabricated using
      two identical silver halide optical fibers for accurate thermometry without
      complicated calibration processes. In this study, we measured the output voltages
      of signal and reference probes according to temperature variation over a
      temperature range from 25 to 225  degrees C. To decide the temperature of the
      water, the difference between the amounts of infrared radiation emitted from the
      two temperature sensing probes was measured. The response time and the
      reproducibility of the fiber-optic temperature sensor were also obtained.
      Thermometry with the proposed sensor is immune to changes if parameters such as
      offset voltage, ambient temperature, and emissivity of any warm object. In
      particular, the temperature sensing probe with silver halide optical fibers can
      withstand a high temperature/pressure and water-chemistry environment. It is
      expected that the proposed sensor can be further developed to accurately monitor
      temperature in harsh environments.

PMID- 22163712
TI  - Photoinduced electron transfer based ion sensing within an optical fiber.
AB  - We combine suspended-core microstructured optical fibers with the photoinduced
      electron transfer (PET) effect to demonstrate a new type of fluorescent optical
      fiber-dip sensing platform for small volume ion detection. A sensor design based
      on a simple model PET-fluoroionophore system and small core microstructured
      optical fiber capable of detecting sodium ions is demonstrated. The performance
      of the dip sensor operating in a high sodium concentration regime (925 ppm Na(+))
      and for lower sodium concentration environments (18.4 ppm Na(+)) is explored and
      future approaches to improving the sensor's signal stability, sensitivity and
      selectivity are discussed.

PMID- 22163713
TI  - Facial expression recognition based on local binary patterns and kernel
      discriminant isomap.
AB  - Facial expression recognition is an interesting and challenging subject.
      Considering the nonlinear manifold structure of facial images, a new kernel-based
      manifold learning method, called kernel discriminant isometric mapping
      (KDIsomap), is proposed. KDIsomap aims to nonlinearly extract the discriminant
      information by maximizing the interclass scatter while minimizing the intraclass
      scatter in a reproducing kernel Hilbert space. KDIsomap is used to perform
      nonlinear dimensionality reduction on the extracted local binary patterns (LBP)
      facial features, and produce low-dimensional discrimimant embedded data
      representations with striking performance improvement on facial expression
      recognition tasks. The nearest neighbor classifier with the Euclidean metric is
      used for facial expression classification. Facial expression recognition
      experiments are performed on two popular facial expression databases, i.e., the
      JAFFE database and the Cohn-Kanade database. Experimental results indicate that
      KDIsomap obtains the best accuracy of 81.59% on the JAFFE database, and 94.88% on
      the Cohn-Kanade database. KDIsomap outperforms the other used methods such as
      principal component analysis (PCA), linear discriminant analysis (LDA), kernel
      principal component analysis (KPCA), kernel linear discriminant analysis (KLDA)
      as well as kernel isometric mapping (KIsomap).

PMID- 22163714
TI  - Automated data quality assessment of marine sensors.
AB  - The automated collection of data (e.g., through sensor networks) has led to a
      massive increase in the quantity of environmental and other data available. The
      sheer quantity of data and growing need for real-time ingestion of sensor data
      (e.g., alerts and forecasts from physical models) means that automated Quality
      Assurance/Quality Control (QA/QC) is necessary to ensure that the data collected
      is fit for purpose. Current automated QA/QC approaches provide assessments based
      upon hard classifications of the gathered data; often as a binary decision of
      good or bad data that fails to quantify our confidence in the data for use in
      different applications. We propose a novel framework for automated data quality
      assessments that uses Fuzzy Logic to provide a continuous scale of data quality.
      This continuous quality scale is then used to compute error bars upon the data,
      which quantify the data uncertainty and provide a more meaningful measure of the
      data's fitness for purpose in a particular application compared with hard quality
      classifications. The design principles of the framework are presented and enable
      both data statistics and expert knowledge to be incorporated into the uncertainty
      assessment. We have implemented and tested the framework upon a real time
      platform of temperature and conductivity sensors that have been deployed to
      monitor the Derwent Estuary in Hobart, Australia. Results indicate that the error
      bars generated from the Fuzzy QA/QC implementation are in good agreement with the
      error bars manually encoded by a domain expert.

PMID- 22163715
TI  - Intercomparisons of nine sky brightness detectors.
AB  - Nine Sky Quality Meters (SQMs) have been intercompared during a night time
      measurement campaign held in the Netherlands in April 2011. Since then the nine
      SQMs have been distributed across The Netherlands and form the Dutch network for
      monitoring night sky brightness. The goal of the intercomparison was to infer
      mutual calibration factors and obtain insight into the variability of the SQMs
      under different meteorological situations. An ensemble average is built from the
      individual measurements and used as a reference to infer the mutual calibration
      factors. Data required additional synchronization prior to the calibration
      determination, because the effect of moving clouds combined with small
      misalignments emerges as time jitter in the measurements. Initial scatter of the
      individual instruments lies between +/-14%. Individual night time sums range from
      -16% to +20%. Intercalibration reduces this to 0.5%, and -7% to +9%,
      respectively. During the campaign the smallest luminance measured was 0.657 +/-
      0.003 mcd/m(2) on 12 April, and the largest value was 5.94 +/- 0.03 mcd/m(2) on 2
      April. During both occurrences interfering circumstances like snow cover or
      moonlight were absent.

PMID- 22163716
TI  - Cell docking, movement and cell-cell interactions of heterogeneous cell
      suspensions in a cell manipulation microdevice.
AB  - This study demonstrates a novel cell manipulation microdevice for cell docking,
      culturing, cell-cell contact and interaction by microfluidic manipulation of
      heterogeneous cell suspensions. Heterogeneous cell suspensions include disparate
      blood cells of natural killer cells and leukemia cancer cells for immune cell
      transplantation therapy. However, NK cell alloreactivity from different healthy
      donors present various recovery response levels. Little is still known about the
      interactions and cytotoxicity effects between donor NK cells and recipient cancer
      cells. The cell-based micro device first showed the capability of cell docking,
      movement, contact and cell-cell interaction with respect to cell cytotoxicity of
      NK cells against cancer cells. With various flow tests for live cell loading,
      flow rates of 10 MUL/h were chosen for injection in the central and side flows
      such that both types of suspension cells could be gently docked at the gap
      structure in a reaction zone. The trapping number of particles and cells was
      linearly proportional to the gap length. Finally, the cytotoxicity of around 40%
      was found to be similar in the case of dilute cells and a large cell population.
      As a result, the cell manipulation microdevice has been validated for live
      suspensions of natural killer and cancer cells, and exhibited the capability to
      measure the cytotoxicity of dilute cell suspensions.

PMID- 22163717
TI  - Adaptive road crack detection system by pavement classification.
AB  - This paper presents a road distress detection system involving the phases needed
      to properly deal with fully automatic road distress assessment. A vehicle
      equipped with line scan cameras, laser illumination and acquisition HW-SW is used
      to storage the digital images that will be further processed to identify road
      cracks. Pre-processing is firstly carried out to both smooth the texture and
      enhance the linear features. Non-crack features detection is then applied to mask
      areas of the images with joints, sealed cracks and white painting, that usually
      generate false positive cracking. A seed-based approach is proposed to deal with
      road crack detection, combining Multiple Directional Non-Minimum Suppression
      (MDNMS) with a symmetry check. Seeds are linked by computing the paths with the
      lowest cost that meet the symmetry restrictions. The whole detection process
      involves the use of several parameters. A correct setting becomes essential to
      get optimal results without manual intervention. A fully automatic approach by
      means of a linear SVM-based classifier ensemble able to distinguish between up to
      10 different types of pavement that appear in the Spanish roads is proposed. The
      optimal feature vector includes different texture-based features. The parameters
      are then tuned depending on the output provided by the classifier. Regarding non
      crack features detection, results show that the introduction of such module
      reduces the impact of false positives due to non-crack features up to a factor of
      2. In addition, the observed performance of the crack detection system is
      significantly boosted by adapting the parameters to the type of pavement.

PMID- 22163718
TI  - Numerical optimization of a microfluidic assisted microarray for the detection of
      biochemical interactions.
AB  - Finite element method analysis was applied to the characterization of the
      biomolecular interactions taking place in a microfluidic assisted microarray.
      Numerical simulations have been used for the optimization of geometrical and
      physical parameters of the sensing device. Different configurations have been
      analyzed and general considerations have been derived. We have shown that a
      parallel disposition of the sensing area allows the homogeneous formation of the
      target molecular complex in all the active zones of the microarray. Stationary
      and time dependent results have also been obtained.

PMID- 22163719
TI  - Terbium to quantum dot FRET bioconjugates for clinical diagnostics: influence of
      human plasma on optical and assembly properties.
AB  - Forster resonance energy transfer (FRET) from luminescent terbium complexes (LTC)
      as donors to semiconductor quantum dots (QDs) as acceptors allows extraordinary
      large FRET efficiencies due to the long Forster distances afforded. Moreover,
      time-gated detection permits an efficient suppression of autofluorescent
      background leading to sub-picomolar detection limits even within multiplexed
      detection formats. These characteristics make FRET-systems with LTC and QDs
      excellent candidates for clinical diagnostics. So far, such proofs of principle
      for highly sensitive multiplexed biosensing have only been performed under
      optimized buffer conditions and interactions between real-life clinical media
      such as human serum or plasma and LTC-QD-FRET-systems have not yet been taken
      into account. Here we present an extensive spectroscopic analysis of absorption,
      excitation and emission spectra along with the luminescence decay times of both
      the single components as well as the assembled FRET-systems in TRIS-buffer, TRIS
      buffer with 2% bovine serum albumin, and fresh human plasma. Moreover, we
      evaluated homogeneous LTC-QD FRET assays in QD conjugates assembled with either
      the well-known, specific biotin-streptavidin biological interaction or,
      alternatively, the metal-affinity coordination of histidine to zinc. In the case
      of conjugates assembled with biotin-streptavidin no significant interference with
      the optical and binding properties occurs whereas the histidine-zinc system
      appears to be affected by human plasma.

PMID- 22163720
TI  - Design of highly sensitive C2H5OH sensors using self-assembled ZnO
      nanostructures.
AB  - Various ZnO nanostructures such as porous nanorods and two hierarchical
      structures consisting of porous nanosheets or crystalline nanorods were prepared
      by the reaction of mixtures of oleic-acid-dissolved ethanol solutions and aqueous
      dissolved Zn-precursor solutions in the presence of NaOH. All three ZnO
      nanostructures showed sensitive and selective detection of C(2)H(5)OH. In
      particular, ultra-high responses (R(a)/R(g) = ~1,200, R(a): resistance in air,
      R(g): resistance in gas) to 100 ppm C(2)H(5)OH was attained using porous nanorods
      and hierarchical structures assembled from porous nanosheets, which is one of the
      highest values reported in the literature. The gas response and linearity of gas
      sensors were discussed in relation to the size, surface area, and porosity of the
      nanostructures.

PMID- 22163721
TI  - Coexistence of WiFi and WiMAX systems based on PS-request protocols.
AB  - We introduce both the coexistence zone within the WiMAX frame structure and a PS
      Request protocol for the coexistence of WiFi and WiMAX systems sharing a
      frequency band. Because we know that the PS-Request protocol has drawbacks, we
      propose a revised PS-Request protocol to improve the performance. Two PS-Request
      protocols are based on the time division operation (TDO) of WiFi system and WiMAX
      system to avoid the mutual interference, and use the vestigial power management
      (PwrMgt) bit within the Frame Control field of the frames transmitted by a WiFi
      AP. The performance of the revised PS-Request protocol is evaluated by computer
      simulation, and compared to those of the cases without a coexistence protocol and
      to the original PS-Request protocol.

PMID- 22163722
TI  - Authenticity preservation with histogram-based reversible data hiding and
      quadtree concepts.
AB  - With the widespread use of identification systems, establishing authenticity with
      sensors has become an important research issue. Among the schemes for making
      authenticity verification based on information security possible, reversible data
      hiding has attracted much attention during the past few years. With its
      characteristics of reversibility, the scheme is required to fulfill the goals
      from two aspects. On the one hand, at the encoder, the secret information needs
      to be embedded into the original image by some algorithms, such that the output
      image will resemble the input one as much as possible. On the other hand, at the
      decoder, both the secret information and the original image must be correctly
      extracted and recovered, and they should be identical to their embedding
      counterparts. Under the requirement of reversibility, for evaluating the
      performance of the data hiding algorithm, the output image quality, named
      imperceptibility, and the number of bits for embedding, called capacity, are the
      two key factors to access the effectiveness of the algorithm. Besides, the size
      of side information for making decoding possible should also be evaluated. Here
      we consider using the characteristics of original images for developing our
      method with better performance. In this paper, we propose an algorithm that has
      the ability to provide more capacity than conventional algorithms, with similar
      output image quality after embedding, and comparable side information produced.
      Simulation results demonstrate the applicability and better performance of our
      algorithm.

PMID- 22163724
TI  - Investigation of digital sun sensor technology with an N-shaped slit mask.
AB  - Nowadays sun sensors are being more widely used in satellites to determine the
      sunray orientation, thus development of a new version of sun sensor with lighter
      mass, lower power consumption and smaller size it of considerable interest. This
      paper introduces such a novel digital sun sensor, which is composed of a micro
      electro-mechanical system (MEMS) mask with an N-shaped slit as well as a single
      linear array charge-coupled device (CCD). The sun sensor can achieve the
      measurement of two-axis sunray angles according to the three sun spot images on
      the CCD formed by sun light illumination through the mask. Given the CCD glass
      layer, an iterative algorithm is established to correct the refraction error.
      Thus, system resolution, update rate and other characteristics are improved based
      on the model simulation and system design. The test of sun sensor prototype is
      carried out on a three-axis rotating platform with a sun simulator. The test
      results show that the field of view (FOV) is +/-60 degrees  * +/-60 degrees  and
      the accuracy is 0.08 degrees of arc (3sigma) in the whole FOV. Since the power
      consumption of the prototype is only 300 mW and the update rate is 14 Hz, the
      novel digital sun sensor can be applied broadly in micro/nano-satellites, even
      pico-satellites.

PMID- 22163723
TI  - Biosensing with quantum dots: a microfluidic approach.
AB  - Semiconductor quantum dots (QDs) have served as the basis for signal development
      in a variety of biosensing technologies and in applications using bioprobes. The
      use of QDs as physical platforms to develop biosensors and bioprobes has
      attracted considerable interest. This is largely due to the unique optical
      properties of QDs that make them excellent choices as donors in fluorescence
      resonance energy transfer (FRET) and well suited for optical multiplexing. The
      large majority of QD-based bioprobe and biosensing technologies that have been
      described operate in bulk solution environments, where selective binding events
      at the surface of QDs are often associated with relatively long periods to reach
      a steady-state signal. An alternative approach to the design of biosensor
      architectures may be provided by a microfluidic system (MFS). A MFS is able to
      integrate chemical and biological processes into a single platform and allows for
      manipulation of flow conditions to achieve, by sample transport and mixing,
      reaction rates that are not entirely diffusion controlled. Integrating assays in
      a MFS provides numerous additional advantages, which include the use of very
      small amounts of reagents and samples, possible sample processing before
      detection, ultra-high sensitivity, high throughput, short analysis time, and in
      situ monitoring. Herein, a comprehensive review is provided that addresses the
      key concepts and applications of QD-based microfluidic biosensors with an added
      emphasis on how this combination of technologies provides for innovations in
      bioassay designs. Examples from the literature are used to highlight the many
      advantages of biosensing in a MFS and illustrate the versatility that such a
      platform offers in the design strategy.

PMID- 22163726
TI  - Manufacture and characterization of high Q-factor inductors based on CMOS-MEMS
      techniques.
AB  - A high Q-factor (quality-factor) spiral inductor fabricated by the CMOS
      (complementary metal oxide semiconductor) process and a post-process was
      investigated. The spiral inductor is manufactured on a silicon substrate. A post
      process is used to remove the underlying silicon substrate in order to reduce the
      substrate loss and to enhance the Q-factor of the inductor. The post-process
      adopts RIE (reactive ion etching) to etch the sacrificial oxide layer, and then
      TMAH (tetramethylammonium hydroxide) is employed to remove the silicon substrate
      for obtaining the suspended spiral inductor. The advantage of this post
      processing method is its compatibility with the CMOS process. The performance of
      the spiral inductor is measured by an Agilent 8510C network analyzer and a
      Cascade probe station. Experimental results show that the Q-factor and inductance
      of the spiral inductor are 15 at 15 GHz and 1.8 nH at 1 GHz, respectively.

PMID- 22163725
TI  - Local positioning systems in (game) sports.
AB  - Position data of players and athletes are widely used in sports performance
      analysis for measuring the amounts of physical activities as well as for tactical
      assessments in game sports. However, positioning sensing systems are applied in
      sports as tools to gain objective information of sports behavior rather than as
      components of intelligent spaces (IS). The paper outlines the idea of IS for the
      sports context with special focus to game sports and how intelligent sports
      feedback systems can benefit from IS. Henceforth, the most common location
      sensing techniques used in sports and their practical application are reviewed,
      as location is among the most important enabling techniques for IS. Furthermore,
      the article exemplifies the idea of IS in sports on two applications.

PMID- 22163727
TI  - Support loss and Q factor enhancement for a rocking mass microgyroscope.
AB  - A rocking mass gyroscope (RMG) is a kind of vibrating mass gyroscope with high
      sensitivity, whose driving mode and sensing mode are completely uniform. MEMS RMG
      devices are a research hotspot now because they have the potential to be used in
      space applications. Support loss is the dominant energy loss mechanism
      influencing their high sensitivity. An accurate analytical model of support loss
      for RMGs is presented to enhance their Q factors. The anchor type and support
      loss mechanism of an RMG are analyzed. Firstly, the support loads, powers flowing
      into support structure, and vibration energy of an RMG are all developed. Then
      the analytical model of support loss for the RMG is developed, and its
      sensitivities to the main structural parameters are also analyzed. High-Q design
      guidelines for rocking mass microgyroscopes are deduced. Finally, the analytical
      model is validated by the experimental data and the data from the existing
      literature. The thicknesses of the prototypes are reduced from 240 MUm to 60 MUm,
      while Q factors increase from less than 150 to more than 800. The derived model
      is general and applicable to various beam resonators, providing significant
      insight to the design of high-Q MEMS devices.

PMID- 22163728
TI  - Sonic anemometry to measure natural ventilation in greenhouses.
AB  - The present work has developed a methodology for studying natural ventilation in
      Mediterranean greenhouses by means of sonic anemometry. In addition, specific
      calculation programmes have been designed to enable processing and analysis of
      the data recorded during the experiments. Sonic anemometry allows us to study the
      direction of the airflow at all the greenhouse vents. Knowing through which vents
      the air enters and leaves the greenhouse enables us to establish the airflow
      pattern of the greenhouse under natural ventilation conditions. In the greenhouse
      analysed in this work for Poniente wind (from the southwest), a roof vent
      designed to open towards the North (leeward) could allow a positive interaction
      between the wind and stack effects, improving the ventilation capacity of the
      greenhouse. The cooling effect produced by the mass of turbulent air oscillating
      between inside and outside the greenhouse at the side vents was limited to 2%
      (for high wind speed, u(o) >= 4 m s(-1)) reaching 36.3% when wind speed was lower
      (u(o) = 2 m s(-1)).

PMID- 22163729
TI  - A multi-sensorial hybrid control for robotic manipulation in human-robot
      workspaces.
AB  - Autonomous manipulation in semi-structured environments where human operators can
      interact is an increasingly common task in robotic applications. This paper
      describes an intelligent multi-sensorial approach that solves this issue by
      providing a multi-robotic platform with a high degree of autonomy and the
      capability to perform complex tasks. The proposed sensorial system is composed of
      a hybrid visual servo control to efficiently guide the robot towards the object
      to be manipulated, an inertial motion capture system and an indoor localization
      system to avoid possible collisions between human operators and robots working in
      the same workspace, and a tactile sensor algorithm to correctly manipulate the
      object. The proposed controller employs the whole multi-sensorial system and
      combines the measurements of each one of the used sensors during two different
      phases considered in the robot task: a first phase where the robot approaches the
      object to be grasped, and a second phase of manipulation of the object. In both
      phases, the unexpected presence of humans is taken into account. This paper also
      presents the successful results obtained in several experimental setups which
      verify the validity of the proposed approach.

PMID- 22163730
TI  - An approach for removing redundant data from RFID data streams.
AB  - Radio frequency identification (RFID) systems are emerging as the primary object
      identification mechanism, especially in supply chain management. However, RFID
      naturally generates a large amount of duplicate readings. Removing these
      duplicates from the RFID data stream is paramount as it does not contribute new
      information to the system and wastes system resources. Existing approaches to
      deal with this problem cannot fulfill the real time demands to process the
      massive RFID data stream. We propose a data filtering approach that efficiently
      detects and removes duplicate readings from RFID data streams. Experimental
      results show that the proposed approach offers a significant improvement as
      compared to the existing approaches.

PMID- 22163731
TI  - Development and evaluation of a miniaturized taste sensor chip.
AB  - A miniaturized taste sensor chip was designed for use in a portable-type taste
      sensing system. The fabricated sensor chip (40 mm * 26 mm * 2.2 mm) has multiple
      taste-sensing sites consisting of a poly(hydroxyethyl methacrylate) hydrogel with
      KCl as the electrolyte layer for stability of the membrane potential and
      artificial lipid membranes as the taste sensing elements. The sensor responses to
      the standard taste substances showed high accuracy and good reproducibility,
      which is comparable with the performance of the sensor probe of the
      commercialized taste sensing system. Thus, the fabricated taste sensor chip could
      be used as a key element for the realization of a portable-type taste sensing
      system.

PMID- 22163732
TI  - Cooperative MIMO communication at wireless sensor network: an error correcting
      code approach.
AB  - Cooperative communication in wireless sensor network (WSN) explores the energy
      efficient wireless communication schemes between multiple sensors and data
      gathering node (DGN) by exploiting multiple input multiple output (MIMO) and
      multiple input single output (MISO) configurations. In this paper, an energy
      efficient cooperative MIMO (C-MIMO) technique is proposed where low density
      parity check (LDPC) code is used as an error correcting code. The rate of LDPC
      code is varied by varying the length of message and parity bits. Simulation
      results show that the cooperative communication scheme outperforms SISO scheme in
      the presence of LDPC code. LDPC codes with different code rates are compared
      using bit error rate (BER) analysis. BER is also analyzed under different
      Nakagami fading scenario. Energy efficiencies are compared for different targeted
      probability of bit error p(b). It is observed that C-MIMO performs more
      efficiently when the targeted p(b) is smaller. Also the lower encoding rate for
      LDPC code offers better error characteristics.

PMID- 22163733
TI  - Coverage assessment and target tracking in 3D domains.
AB  - Recent advances in integrated electronic devices motivated the use of Wireless
      Sensor Networks (WSNs) in many applications including domain surveillance and
      mobile target tracking, where a number of sensors are scattered within a
      sensitive region to detect the presence of intruders and forward related events
      to some analysis center(s). Obviously, sensor deployment should guarantee an
      optimal event detection rate and should reduce coverage holes. Most of the
      coverage control approaches proposed in the literature deal with two-dimensional
      zones and do not develop strategies to handle coverage in three-dimensional
      domains, which is becoming a requirement for many applications including water
      monitoring, indoor surveillance, and projectile tracking. This paper proposes
      efficient techniques to detect coverage holes in a 3D domain using a finite set
      of sensors, repair the holes, and track hostile targets. To this end, we use the
      concepts of Voronoi tessellation, Vietoris complex, and retract by deformation.
      We show in particular that, through a set of iterative transformations of the
      Vietoris complex corresponding to the deployed sensors, the number of coverage
      holes can be computed with a low complexity. Mobility strategies are also
      proposed to repair holes by moving appropriately sensors towards the uncovered
      zones. The tracking objective is to set a non-uniform WSN coverage within the
      monitored domain to allow detecting the target(s) by the set of sensors. We show,
      in particular, how the proposed algorithms adapt to cope with obstacles.
      Simulation experiments are carried out to analyze the efficiency of the proposed
      models. To our knowledge, repairing and tracking is addressed for the first time
      in 3D spaces with different sensor coverage schemes.

PMID- 22163734
TI  - Fault diagnosis for micro-gas turbine engine sensors via wavelet entropy.
AB  - Sensor fault diagnosis is necessary to ensure the normal operation of a gas
      turbine system. However, the existing methods require too many resources and this
      need can't be satisfied in some occasions. Since the sensor readings are directly
      affected by sensor state, sensor fault diagnosis can be performed by extracting
      features of the measured signals. This paper proposes a novel fault diagnosis
      method for sensors based on wavelet entropy. Based on the wavelet theory, wavelet
      decomposition is utilized to decompose the signal in different scales. Then the
      instantaneous wavelet energy entropy (IWEE) and instantaneous wavelet singular
      entropy (IWSE) are defined based on the previous wavelet entropy theory.
      Subsequently, a fault diagnosis method for gas turbine sensors is proposed based
      on the results of a numerically simulated example. Then, experiments on this
      method are carried out on a real micro gas turbine engine. In the experiment,
      four types of faults with different magnitudes are presented. The experimental
      results show that the proposed method for sensor fault diagnosis is efficient.

PMID- 22163735
TI  - In situ monitoring of temperature inside lithium-ion batteries by flexible micro
      temperature sensors.
AB  - Lithium-ion secondary batteries are commonly used in electric vehicles, smart
      phones, personal digital assistants (PDA), notebooks and electric cars. These
      lithium-ion secondary batteries must charge and discharge rapidly, causing the
      interior temperature to rise quickly, raising a safety issue. Over-charging
      results in an unstable voltage and current, causing potential safety problems,
      such as thermal runaways and explosions. Thus, a micro flexible temperature
      sensor for the in in-situ monitoring of temperature inside a lithium-ion
      secondary battery must be developed. In this work, flexible micro temperature
      sensors were integrated into a lithium-ion secondary battery using the micro
      electro-mechanical systems (MEMS) process for monitoring temperature in situ.

PMID- 22163736
TI  - Enzyme-polymers conjugated to quantum-dots for sensing applications.
AB  - In the present research, the concept of developing a novel system based on
      polymer-enzyme macromolecules was tested by coupling carboxylic acid
      functionalized poly(vinyl alcohol) (PVA-COOH) to glucose oxidase (GOx) followed
      by the bioconjugation with CdS quantum-dots (QD). The resulting organic-inorganic
      nanohybrids were characterized by UV-visible spectroscopy, infrared spectroscopy,
      Photoluminescence spectroscopy (PL) and transmission electron microscopy (TEM).
      The spectroscopy results have clearly shown that the polymer-enzyme
      macromolecules (PVA-COOH/GOx) were synthesized by the proposed zero-length linker
      route. Moreover, they have performed as successful capping agents for the
      nucleation and constrained growth of CdS quantum-dots via aqueous colloidal
      chemistry. The TEM images associated with the optical absorption results have
      indicated the formation of CdS nanocrystals with estimated diameters of about 3.0
      nm. The "blue-shift" in the visible absorption spectra and the PL values have
      provided strong evidence that the fluorescent CdS nanoparticles were produced in
      the quantum-size confinement regime. Finally, the hybrid system was biochemically
      assayed by injecting the glucose substrate and detecting the formation of
      peroxide with the enzyme horseradish peroxidase (HRP). Thus, the polymer-enzyme
      QD hybrid has behaved as a nanostructured sensor for glucose detecting.

PMID- 22163737
TI  - Application of terahertz radiation to soil measurements: initial results.
AB  - Developing soil sensors with the possibility of continuous online measurement is
      a major challenge in soil science. Terahertz (THz) electromagnetic radiation may
      provide the opportunity for the measurement of organic material density, water
      content and other soil parameters at different soil depths. Penetration depth and
      information content is important for a functional soil sensor. Therefore, we
      present initial research on the analysis of absorption coefficients of four
      different soil samples by means of THz transmission measurements. An optimized
      soil sample holder to determine absorption coefficients was used. This setup
      improves data acquisition because interface reflections can be neglected.
      Frequencies of 340 GHz to 360 GHz and 1.627 THz to 2.523 THz provided information
      about an existing frequency dependency. The results demonstrate the potential of
      this THz approach for both soil analysis and imaging of buried objects.
      Therefore, the THz approach allows different soil samples to be distinguished
      according to their different absorption properties so that relations among soil
      parameters may be established in future.

PMID- 22163738
TI  - Collaborative localization algorithms for wireless sensor networks with reduced
      localization error.
AB  - Localization is an important research issue in Wireless Sensor Networks (WSNs).
      Though Global Positioning System (GPS) can be used to locate the position of the
      sensors, unfortunately it is limited to outdoor applications and is costly and
      power consuming. In order to find location of sensor nodes without help of GPS,
      collaboration among nodes is highly essential so that localization can be
      accomplished efficiently. In this paper, novel localization algorithms are
      proposed to find out possible location information of the normal nodes in a
      collaborative manner for an outdoor environment with help of few beacons and
      anchor nodes. In our localization scheme, at most three beacon nodes should be
      collaborated to find out the accurate location information of any normal node.
      Besides, analytical methods are designed to calculate and reduce the localization
      error using probability distribution function. Performance evaluation of our
      algorithm shows that there is a tradeoff between deployed number of beacon nodes
      and localization error, and average localization time of the network can be
      increased with increase in the number of normal nodes deployed over a region.

PMID- 22163739
TI  - Efficient smart CMOS camera based on FPGAs oriented to embedded image processing.
AB  - This article describes an image processing system based on an intelligent ad-hoc
      camera, whose two principle elements are a high speed 1.2 megapixel Complementary
      Metal Oxide Semiconductor (CMOS) sensor and a Field Programmable Gate Array
      (FPGA). The latter is used to control the various sensor parameter configurations
      and, where desired, to receive and process the images captured by the CMOS
      sensor. The flexibility and versatility offered by the new FPGA families makes it
      possible to incorporate microprocessors into these reconfigurable devices, and
      these are normally used for highly sequential tasks unsuitable for
      parallelization in hardware. For the present study, we used a Xilinx XC4VFX12
      FPGA, which contains an internal Power PC (PPC) microprocessor. In turn, this
      contains a standalone system which manages the FPGA image processing hardware and
      endows the system with multiple software options for processing the images
      captured by the CMOS sensor. The system also incorporates an Ethernet channel for
      sending processed and unprocessed images from the FPGA to a remote node.
      Consequently, it is possible to visualize and configure system operation and
      captured and/or processed images remotely.

PMID- 22163740
TI  - Accuracy and feasibility of optoelectronic sensors for weed mapping in wide row
      crops.
AB  - The main objectives of this study were to assess the accuracy of a ground-based
      weed mapping system that included optoelectronic sensors for weed detection, and
      to determine the sampling resolution required for accurate weed maps in maize
      crops. The optoelectronic sensors were located in the inter-row area of maize to
      distinguish weeds against soil background. The system was evaluated in three
      maize fields in the early spring. System verification was performed with highly
      reliable data from digital images obtained in a regular 12 m * 12 m grid
      throughout the three fields. The comparison in all these sample points showed a
      good relationship (83% agreement on average) between the data of weed
      presence/absence obtained from the optoelectronic mapping system and the values
      derived from image processing software ("ground truth"). Regarding the
      optimization of sampling resolution, the comparison between the detailed maps
      (all crop rows with sensors separated 0.75 m) with maps obtained with various
      simulated distances between sensors (from 1.5 m to 6.0 m) indicated that a 4.5 m
      distance (equivalent to one in six crop rows) would be acceptable to construct
      accurate weed maps. This spatial resolution makes the system cheap and robust
      enough to generate maps of inter-row weeds.

PMID- 22163741
TI  - New finger biometric method using near infrared imaging.
AB  - In this paper, we propose a new finger biometric method. Infrared finger images
      are first captured, and then feature extraction is performed using a modified
      gaussian high-pass filter through binarization, local binary pattern (LBP), and
      local derivative pattern (LDP) methods. Infrared finger images include the
      multimodal features of finger veins and finger geometries. Instead of extracting
      each feature using different methods, the modified gaussian high-pass filter is
      fully convolved. Therefore, the extracted binary patterns of finger images
      include the multimodal features of veins and finger geometries. Experimental
      results show that the proposed method has an error rate of 0.13%.

PMID- 22163742
TI  - Non destructive defect detection by spectral density analysis.
AB  - The potential nondestructive diagnostics of solid objects is discussed in this
      article. The whole process is accomplished by consecutive steps involving
      software analysis of the vibration power spectrum (eventually acoustic emissions)
      created during the normal operation of the diagnosed device or under unexpected
      situations. Another option is to create an artificial pulse, which can help us to
      determine the actual state of the diagnosed device. The main idea of this method
      is based on the analysis of the current power spectrum density of the received
      signal and its postprocessing in the Matlab environment with a following sample
      comparison in the Statistica software environment. The last step, which is
      comparison of samples, is the most important, because it is possible to determine
      the status of the examined object at a given time. Nowadays samples are compared
      only visually, but this method can't produce good results. Further the presented
      filter can choose relevant data from a huge group of data, which originate from
      applying FFT (Fast Fourier Transform). On the other hand, using this approach
      they can be subjected to analysis with the assistance of a neural network. If
      correct and high-quality starting data are provided to the initial network, we
      are able to analyze other samples and state in which condition a certain object
      is. The success rate of this approximation, based on our testing of the solution,
      is now 85.7%. With further improvement of the filter, it could be even greater.
      Finally it is possible to detect defective conditions or upcoming limiting states
      of examined objects/materials by using only one device which contains HW and SW
      parts. This kind of detection can provide significant financial savings in
      certain cases (such as continuous casting of iron where it could save hundreds of
      thousands of USD).

PMID- 22163743
TI  - An MILP-based cross-layer optimization for a multi-reader arbitration in the UHF
      RFID system.
AB  - In RFID systems, the performance of each reader such as interrogation range and
      tag recognition rate may suffer from interferences from other readers. Since the
      reader interference can be mitigated by output signal power control, spectral
      and/or temporal separation among readers, the system performance depends on how
      to adapt the various reader arbitration metrics such as time, frequency, and
      output power to the system environment. However, complexity and difficulty of the
      optimization problem increase with respect to the variety of the arbitration
      metrics. Thus, most proposals in previous study have been suggested to primarily
      prevent the reader collision with consideration of one or two arbitration
      metrics. In this paper, we propose a novel cross-layer optimization design based
      on the concept of combining time division, frequency division, and power control
      not only to solve the reader interference problem, but also to achieve the
      multiple objectives such as minimum interrogation delay, maximum reader
      utilization, and energy efficiency. Based on the priority of the multiple
      objectives, our cross-layer design optimizes the system sequentially by means of
      the mixed-integer linear programming. In spite of the multi-stage optimization,
      the optimization design is formulated as a concise single mathematical form by
      properly assigning a weight to each objective. Numerical results demonstrate the
      effectiveness of the proposed optimization design.

PMID- 22163744
TI  - Classification and quality evaluation of tobacco leaves based on image processing
      and fuzzy comprehensive evaluation.
AB  - Most of classification, quality evaluation or grading of the flue-cured tobacco
      leaves are manually operated, which relies on the judgmental experience of
      experts, and inevitably limited by personal, physical and environmental factors.
      The classification and the quality evaluation are therefore subjective and
      experientially based. In this paper, an automatic classification method of
      tobacco leaves based on the digital image processing and the fuzzy sets theory is
      presented. A grading system based on image processing techniques was developed
      for automatically inspecting and grading flue-cured tobacco leaves. This system
      uses machine vision for the extraction and analysis of color, size, shape and
      surface texture. Fuzzy comprehensive evaluation provides a high level of
      confidence in decision making based on the fuzzy logic. The neural network is
      used to estimate and forecast the membership function of the features of tobacco
      leaves in the fuzzy sets. The experimental results of the two-level fuzzy
      comprehensive evaluation (FCE) show that the accuracy rate of classification is
      about 94% for the trained tobacco leaves, and the accuracy rate of the non
      trained tobacco leaves is about 72%. We believe that the fuzzy comprehensive
      evaluation is a viable way for the automatic classification and quality
      evaluation of the tobacco leaves.

PMID- 22163745
TI  - Sparsity-based spatial interpolation in wireless sensor networks.
AB  - In wireless sensor networks, due to environmental limitations or bad wireless
      channel conditions, not all sensor samples can be successfully gathered at the
      sink. In this paper, we try to recover these missing samples without
      retransmission. The missing samples estimation problem is mathematically
      formulated as a 2-D spatial interpolation. Assuming the 2-D sensor data can be
      sparsely represented by a dictionary, a sparsity-based recovery approach by
      solving for l(1) norm minimization is proposed. It is shown that these missing
      samples can be reasonably recovered based on the null space property of the
      dictionary. This property also points out the way to choose an appropriate
      sparsifying dictionary to further reduce the recovery errors. The simulation
      results on synthetic and real data demonstrate that the proposed approach can
      recover the missing data reasonably well and that it outperforms the weighted
      average interpolation methods when the data change relatively fast or blocks of
      samples are lost. Besides, there exists a range of missing rates where the
      proposed approach is robust to missing block sizes.

PMID- 22163746
TI  - Laboratory calibration of a field imaging spectrometer system.
AB  - A new Field Imaging Spectrometer System (FISS) based on a cooling area CCD was
      developed. This paper describes the imaging principle, structural design, and
      main parameters of the FISS sensor. The FISS was spectrally calibrated with a
      double grating monochromator to determine the center wavelength and FWHM of each
      band. Calibration results showed that the spectral range of the FISS system is
      437-902 nm, the number of channels is 344 and the spectral resolution of each
      channel is better than 5 nm. An integrating sphere was used to achieve absolute
      radiometric calibration of the FISS with less than 5% calibration error for each
      band. There are 215 channels with signal to noise ratios (SNRs) greater than 500
      (62.5% of the bands). The results demonstrated that the FISS has achieved high
      performance that assures the feasibility of its practical use in various fields.

PMID- 22163747
TI  - Modeling of nonlinear aggregation for information fusion systems with outliers
      based on the Choquet integral.
AB  - Modern information fusion systems essentially associate decision-making processes
      with multi-sensor systems. Precise decision-making processes depend upon
      aggregating useful information extracted from large numbers of messages or large
      datasets; meanwhile, the distributed multi-sensor systems which employ several
      geographically separated local sensors are required to provide sufficient
      messages or data with similar and/or dissimilar characteristics. These kinds of
      information fusion techniques have been widely investigated and used for
      implementing several information retrieval systems. However, the results obtained
      from the information fusion systems vary in different situations and performing
      intelligent aggregation and fusion of information from a distributed multi
      source, multi-sensor network is essentially an optimization problem. A flexible
      and versatile framework which is able to solve complex global optimization
      problems is a valuable alternative to traditional information fusion.
      Furthermore, because of the highly dynamic and volatile nature of the information
      flow, a swift soft computing technique is imperative to satisfy the demands and
      challenges. In this paper, a nonlinear aggregation based on the Choquet integral
      (NACI) model is considered for information fusion systems that include outliers
      under inherent interaction among feature attributes. The estimation of
      interaction coefficients for the proposed model is also performed via a modified
      algorithm based on particle swarm optimization with quantum-behavior (QPSO) and
      the high breakdown value estimator, least trimmed squares (LTS). From simulation
      results, the proposed MQPSO algorithm with LTS (named LTS-MQPSO) readily corrects
      the deviations caused by outliers and swiftly achieves convergence in estimating
      the parameters of the proposed NACI model for the information fusion systems with
      outliers.

PMID- 22163748
TI  - A non-invasive thermal drift compensation technique applied to a spin-valve
      magnetoresistive current sensor.
AB  - A compensation method for the sensitivity drift of a magnetoresistive (MR)
      Wheatstone bridge current sensor is proposed. The technique was carried out by
      placing a ruthenium temperature sensor and the MR sensor to be compensated inside
      a generalized impedance converter circuit (GIC). No internal modification of the
      sensor bridge arms is required so that the circuit is capable of compensating
      practical industrial sensors. The method is based on the temperature modulation
      of the current supplied to the bridge, which improves previous solutions based on
      constant current compensation. Experimental results are shown using a
      microfabricated spin-valve MR current sensor. The temperature compensation has
      been solved in the interval from 0  degrees C to 70  degrees C measuring currents
      from -10 A to +10 A.

PMID- 22163749
TI  - Performance of an ultrasonic ranging sensor in apple tree canopies.
AB  - Electronic canopy characterization is an important issue in tree crop management.
      Ultrasonic and optical sensors are the most used for this purpose. The objective
      of this work was to assess the performance of an ultrasonic sensor under
      laboratory and field conditions in order to provide reliable estimations of
      distance measurements to apple tree canopies. To this purpose, a methodology has
      been designed to analyze sensor performance in relation to foliage ranging and to
      interferences with adjacent sensors when working simultaneously. Results show
      that the average error in distance measurement using the ultrasonic sensor in
      laboratory conditions is +/-0.53 cm. However, the increase of variability in
      field conditions reduces the accuracy of this kind of sensors when estimating
      distances to canopies. The average error in such situations is +/-5.11 cm. When
      analyzing interferences of adjacent sensors 30 cm apart, the average error is +/
      17.46 cm. When sensors are separated 60 cm, the average error is +/-9.29 cm. The
      ultrasonic sensor tested has been proven to be suitable to estimate distances to
      the canopy in field conditions when sensors are 60 cm apart or more and could,
      therefore, be used in a system to estimate structural canopy parameters in
      precision horticulture.

PMID- 22163750
TI  - Laser chemosensor with rapid responsivity and inherent memory based on a polymer
      of intrinsic microporosity.
AB  - This work explores the use of a polymer of intrinsic microporosity (PIM-1) as the
      active layer within a laser sensor to detect nitroaromatic-based explosive
      vapors. We show successful detection of dinitrobenzene (DNB) by monitoring the
      real-time photoluminescence. We also show that PIM-1 has an inherent memory, so
      that it accumulates the analyte during exposure. In addition, the optical gain
      and refractive index of the polymer were studied by amplified spontaneous
      emission and variable-angle ellipsometry, respectively. A second-order
      distributed feedback PIM-1 laser sensor was fabricated and found to show an
      increase in laser threshold of 2.5 times and a reduction of the laser slope
      efficiency by 4.4 times after a 5-min exposure to the DNB vapor. For pumping at 2
      times threshold, the lasing action was stopped within 30 s indicating that PIM-1
      has a very fast responsivity and as such has a potential sensing ability for
      ultra-low-concentration explosives.

PMID- 22163751
TI  - A transflective nano-wire grid polarizer based fiber-optic sensor.
AB  - A transflective nano-wire grid polarizer is fabricated on a single mode fiber tip
      by focused ion beam machining. In contrast to conventional absorptive in-line
      polarizers, the wire grids reflect TE-mode, while transmitting TM-mode light so
      that no light power is discarded. A reflection contrast of 13.7 dB and a
      transmission contrast of 4.9 dB are achieved in the 1,550 nm telecom band using a
      200-nm wire grid fiber polarizer. With the help of an optic circulator, the
      polarization states of both the transmissive and reflective lights in the fiber
      may be monitored simultaneously. A kind of robust fiber optic sensor is thus
      proposed that could withstand light power variations. To verify the idea, a fiber
      pressure sensor with the sensitivity of 0.24 rad/N is demonstrated. The
      corresponding stress-optic coefficient of the fiber is measured. In addition to
      pressure sensing, this technology could be applied in detecting any polarization
      state change induced by magnetic fields, electric currents and so on.

PMID- 22163752
TI  - Patrol detection for replica attacks on wireless sensor networks.
AB  - Replica attack is a critical concern in the security of wireless sensor networks.
      We employ mobile nodes as patrollers to detect replicas distributed in different
      zones in a network, in which a basic patrol detection protocol and two detection
      algorithms for stationary and mobile modes are presented. Then we perform
      security analysis to discuss the defense strategies against the possible attacks
      on the proposed detection protocol. Moreover, we show the advantages of the
      proposed protocol by discussing and comparing the communication cost and
      detection probability with some existing methods.

PMID- 22163753
TI  - W-MAC: a workload-aware MAC protocol for heterogeneous convergecast in wireless
      sensor networks.
AB  - The power consumption and latency of existing MAC protocols for wireless sensor
      networks (WSNs) are high in heterogeneous convergecast, where each sensor node
      generates different amounts of data in one convergecast operation. To solve this
      problem, we present W-MAC, a workload-aware MAC protocol for heterogeneous
      convergecast in WSNs. A subtree-based iterative cascading scheduling mechanism
      and a workload-aware time slice allocation mechanism are proposed to minimize the
      power consumption of nodes, while offering a low data latency. In addition, an
      efficient schedule adjustment mechanism is provided for adapting to data traffic
      variation and network topology change. Analytical and simulation results show
      that the proposed protocol provides a significant energy saving and latency
      reduction in heterogeneous convergecast, and can effectively support data
      aggregation to further improve the performance.

PMID- 22163754
TI  - Non-destructive techniques based on eddy current testing.
AB  - Non-destructive techniques are used widely in the metal industry in order to
      control the quality of materials. Eddy current testing is one of the most
      extensively used non-destructive techniques for inspecting electrically
      conductive materials at very high speeds that does not require any contact
      between the test piece and the sensor. This paper includes an overview of the
      fundamentals and main variables of eddy current testing. It also describes the
      state-of-the-art sensors and modern techniques such as multi-frequency and pulsed
      systems. Recent advances in complex models towards solving crack-sensor
      interaction, developments in instrumentation due to advances in electronic
      devices, and the evolution of data processing suggest that eddy current testing
      systems will be increasingly used in the future.

PMID- 22163755
TI  - Microstructured optical fiber sensors embedded in a laminate composite for smart
      material applications.
AB  - Fiber Bragg gratings written in highly birefringent microstructured optical fiber
      with a dedicated design are embedded in a composite fiber-reinforced polymer. The
      Bragg peak wavelength shifts are measured under controlled axial and transversal
      strain and during thermal cycling of the composite sample. We obtain a
      sensitivity to transversal strain that exceeds values reported earlier in
      literature by one order of magnitude. Our results evidence the relevance of using
      microstructured optical fibers for structural integrity monitoring of composite
      material structures.

PMID- 22163756
TI  - Development of micro-heaters with optimized temperature compensation design for
      gas sensors.
AB  - One of the key components of a chemical gas sensor is a MEMS micro-heater. Micro
      heaters are used in both semiconductor gas sensors and NDIR gas sensors; however
      they each require different heat dissipation characteristics. For the
      semiconductor gas sensors, a uniform temperature is required over a wide area of
      the heater. On the other hand, for the NDIR gas sensor, the micro-heater needs
      high levels of infrared radiation in order to increase sensitivity. In this
      study, a novel design of a poly-Si micro-heater is proposed to improve the
      uniformity of heat dissipation on the heating plate. Temperature uniformity of
      the micro-heater is achieved by compensating for the variation in power
      consumption around the perimeter of the heater. With the power compensated
      design, the uniform heating area is increased by 2.5 times and the average
      temperature goes up by 40  degrees C. Therefore, this power compensated micro
      heater design is suitable for a semiconductor gas sensor. Meanwhile, the poly-Si
      micro-heater without compensation shows a higher level of infrared radiation
      under equal power consumption conditions. This indicates that the micro-heater
      without compensation is more suitable for a NDIR gas sensor. Furthermore, the
      micro-heater shows a short response time of less than 20 ms, indicating a very
      high efficiency of pulse driving.

PMID- 22163757
TI  - Analysis of coaxial soil cell in reflection and transmission.
AB  - Accurate measurement of moisture content is a prime requirement in hydrological,
      geophysical and biogeochemical research as well as for material characterization
      and process control. Within these areas, accurate measurements of the surface
      area and bound water content is becoming increasingly important for providing
      answers to many fundamental questions ranging from characterization of cotton
      fiber maturity, to accurate characterization of soil water content in soil water
      conservation research to bio-plant water utilization to chemical reactions and
      diffusions of ionic species across membranes in cells as well as in the dense
      suspensions that occur in surface films. In these bound water materials, the
      errors in the traditional time-domain-reflectometer, "TDR", exceed the range of
      the full span of the material's permittivity that is being measured. Thus, there
      is a critical need to re-examine the TDR system and identify where the errors are
      to direct future research. One promising technique to address the increasing
      demands for higher accuracy water content measurements is utilization of
      electrical permittivity characterization of materials. This technique has enjoyed
      a strong following in the soil-science and geological community through
      measurements of apparent permittivity via time-domain-reflectometery as well in
      many process control applications. Recent research however, is indicating a need
      to increase the accuracy beyond that available from traditional TDR. The most
      logical pathway then becomes a transition from TDR based measurements to network
      analyzer measurements of absolute permittivity that will remove the adverse
      effects that high surface area soils and conductivity impart onto the
      measurements of apparent permittivity in traditional TDR applications. This
      research examines the theoretical basis behind the coaxial probe, from which the
      modern TDR probe originated from, to provide a basis on which to perform absolute
      permittivity measurements. The research reveals currently utilized formulations
      in accepted techniques for permittivity measurements which violate the underlying
      assumptions inherent in the basic models due to the TDR acting as an antenna by
      radiating energy off the end of the probe, rather than returning it back to the
      source as is the current assumption. To remove the effects of radiation from the
      experimental results obtain herein, this research utilized custom designed
      coaxial probes of various diameters and probe lengths by which to test the
      coaxial cell measurement technique for accuracy in determination of absolute
      permittivity. In doing so, the research reveals that the basic models available
      in the literature all omitted a key correction factor that is hypothesized by
      this research as being most likely due to fringe capacitance. To test this
      theory, a Poisson model of a coaxial cell was formulated to calculate the
      effective extra length provided by the fringe capacitance which is then used to
      correct the experimental results such that experimental measurements utilizing
      differing coaxial cell diameters and probe lengths, upon correction with the
      Poisson model derived correction factor, all produce the same results thereby
      lending support for the use of an augmented measurement technique, described
      herein, for measurement of absolute permittivity, as opposed to the traditional
      TDR measurement of apparent permittivity.

PMID- 22163758
TI  - User identification using gait patterns on UbiFloorII.
AB  - This paper presents a system of identifying individuals by their gait patterns.
      We take into account various distinguishable features that can be extracted from
      a user's gait and then divide them into two classes: walking pattern and stepping
      pattern. The conditions we assume are that our target environments are domestic
      areas, the number of users is smaller than 10, and all users ambulate with bare
      feet considering the everyday lifestyle of the Korean home. Under these
      conditions, we have developed a system that identifies individuals' gait patterns
      using our biometric sensor, UbiFloorII. We have created UbiFloorII to collect
      walking samples and created software modules to extract the user's gait pattern.
      To identify the users based on the gait patterns extracted from walking samples
      over UbiFloorII, we have deployed multilayer perceptron network, a feedforward
      artificial neural network model. The results show that both walking pattern and
      stepping pattern extracted from users' gait over the UbiFloorII are
      distinguishable enough to identify the users and that fusing two classifiers at
      the matching score level improves the recognition accuracy. Therefore, our
      proposed system may provide unobtrusive and automatic user identification methods
      in ubiquitous computing environments, particularly in domestic areas.

PMID- 22163759
TI  - Study of temperature characteristics of micromachined suspended coplanar
      waveguides for biosensing applications.
AB  - In the recent development on biosensors, coplanar waveguide based microwave
      dielectric sensors have been attracting more and more attentions. In this paper,
      microwave performance of a suspended coplanar waveguide subject to temperature
      variations, particularly in a small range, is studied. The prototype is realized
      through a MEMS fabrication foundry. The thermal transfer analysis of the device
      is conducted using finite element method, and the microwave properties of the
      device are characterized. One of the results shows that at 20 GHz, the S11 has
      decreased by 7.4%, and S21 has increased by 3.5% when the voltage applied to the
      heaters varies from 9 V to 29 V.

PMID- 22163760
TI  - New generation Sensor Web Enablement.
AB  - Many sensor networks have been deployed to monitor Earth's environment, and more
      will follow in the future. Environmental sensors have improved continuously by
      becoming smaller, cheaper, and more intelligent. Due to the large number of
      sensor manufacturers and differing accompanying protocols, integrating diverse
      sensors into observation systems is not straightforward. A coherent
      infrastructure is needed to treat sensors in an interoperable, platform
      independent and uniform way. The concept of the Sensor Web reflects such a kind
      of infrastructure for sharing, finding, and accessing sensors and their data
      across different applications. It hides the heterogeneous sensor hardware and
      communication protocols from the applications built on top of it. The Sensor Web
      Enablement initiative of the Open Geospatial Consortium standardizes web service
      interfaces and data encodings which can be used as building blocks for a Sensor
      Web. This article illustrates and analyzes the recent developments of the new
      generation of the Sensor Web Enablement specification framework. Further, we
      relate the Sensor Web to other emerging concepts such as the Web of Things and
      point out challenges and resulting future work topics for research on Sensor Web
      Enablement.

PMID- 22163762
TI  - Wireless remote weather monitoring system based on MEMS technologies.
AB  - This study proposes a wireless remote weather monitoring system based on Micro
      Electro-Mechanical Systems (MEMS) and wireless sensor network (WSN) technologies
      comprising sensors for the measurement of temperature, humidity, pressure, wind
      speed and direction, integrated on a single chip. The sensing signals are
      transmitted between the Octopus II-A sensor nodes using WSN technology, following
      amplification and analog/digital conversion (ADC). Experimental results show that
      the resistance of the micro temperature sensor increases linearly with input
      temperature, with an average TCR (temperature coefficient of resistance) value of
      8.2 * 10(-4) ( degrees C(-1)). The resistance of the pressure sensor also
      increases linearly with air pressure, with an average sensitivity value of 3.5 *
      10(-2) (Omega/kPa). The sensitivity to humidity increases with ambient
      temperature due to the effect of temperature on the dielectric constant, which
      was determined to be 16.9, 21.4, 27.0, and 38.2 (pF/%RH) at 27  degrees C, 30 
      degrees C, 40  degrees C, and 50  degrees C, respectively. The velocity of
      airflow is obtained by summing the variations in resistor response as airflow
      passed over the sensors providing sensitivity of 4.2 * 10(-2), 9.2 * 10(-2), 9.7
      * 10(-2) (Omega/ms(-1)) with power consumption by the heating resistor of 0.2,
      0.3, and 0.5 W, respectively. The passage of air across the surface of the flow
      sensors prompts variations in temperature among each of the sensing resistors.
      Evaluating these variations in resistance caused by the temperature change
      enables the measurement of wind direction.

PMID- 22163761
TI  - A nanosensor for TNT detection based on molecularly imprinted polymers and
      surface enhanced Raman scattering.
AB  - We report on a new sensor strategy that integrates molecularly imprinted polymers
      (MIPs) with surface enhanced Raman scattering (SERS). The sensor was developed to
      detect the explosive, 2,4,6-trinitrotoluene (TNT). Micron thick films of sol gel
      derived xerogels were deposited on a SERS-active surface as the sensing layer.
      Xerogels were molecularly imprinted for TNT using non-covalent interactions with
      the polymer matrix. Binding of the TNT within the polymer matrix results in
      unique SERS bands, which allow for detection and identification of the molecule
      in the MIP. This MIP-SERS sensor exhibits an apparent dissociation constant of
      (2.3 +/- 0.3) * 10(-5) M for TNT and a 3 MUM detection limit. The response to TNT
      is reversible and the sensor is stable for at least 6 months. Key challenges,
      including developing a MIP formulation that is stable and integrated with the
      SERS substrate, and ensuring the MIP does not mask the spectral features of the
      target analyte through SERS polymer background, were successfully met. The
      results also suggest the MIP-SERS protocol can be extended to other target
      analytes of interest.

PMID- 22163763
TI  - Subtractive inhibition assay for the detection of E. coli O157:H7 using surface
      plasmon resonance.
AB  - A surface plasmon resonance (SPR) immunosensor was developed for the detection of
      E. coli O157:H7 by means of a new subtractive inhibition assay. In the
      subtractive inhibition assay, E. coli O157:H7 cells and goat polyclonal
      antibodies for E. coli O157:H7 were incubated for a short of time, and then the
      E. coli O157:H7 cells which bound antibodies were removed by a stepwise
      centrifugation process. The remaining free unbound antibodies were detected
      through interaction with rabbit anti-goat IgG polyclonal antibodies immobilized
      on the sensor chip using a BIAcore 3000 biosensor. The results showed that the
      signal was inversely correlated with the concentration of E. coli O157:H7 cells
      in a range from 3.0 * 10(4) to 3.0 * 10(8) cfu/mL with a detection limit of 3.0 *
      10(4) cfu/mL. Compared with direct SPR by immobilizing antibodies on the chip
      surface to capture the bacterial cells and ELISA for E. coli O157:H7 (detection
      limit: both 3.0 * 10(5) cfu/mL in this paper), the detection limit of subtractive
      inhibition assay method was reduced by one order of magnitude. The method
      simplifies bacterial cell detection to protein-protein interaction, which has the
      potential for providing a practical alternative for the monitoring of E. coli
      O157:H7 and other pathogens.

PMID- 22163764
TI  - Sub-micron particle based structures as reconfigurable photonic devices
      controllable by external photonic and magnetic fields.
AB  - In this paper we present the configurations of two nanometer scale structures-
      one of them optically controllable and the second one magnetically controllable.
      The first involves an array of nanoparticles that are made up of two layers
      (i.e., Au on top of a Si layer). The device may exhibits a wide range of
      plasmonic resonance according to external photonic radiation. The second type of
      device involves the usage of sub micron superparamagnetic particles located on a
      suitable structuring grid, that according to the angle of the external magnetic
      field allows control of the length of the structuring grid and therefore control
      the diffraction order of each wavelength.

PMID- 22163765
TI  - Characterisation of the LMS200 laser beam under the influence of blockage
      surfaces. Influence on 3D scanning of tree orchards.
AB  - The geometric characterisation of tree orchards is a high-precision activity
      comprising the accurate measurement and knowledge of the geometry and structure
      of the trees. Different types of sensors can be used to perform this
      characterisation. In this work a terrestrial LIDAR sensor (SICK LMS200) whose
      emission source was a 905-nm pulsed laser diode was used. Given the known
      dimensions of the laser beam cross-section (with diameters ranging from 12 mm at
      the point of emission to 47.2 mm at a distance of 8 m), and the known dimensions
      of the elements that make up the crops under study (flowers, leaves, fruits,
      branches, trunks), it was anticipated that, for much of the time, the laser beam
      would only partially hit a foreground target/object, with the consequent problem
      of mixed pixels or edge effects. Understanding what happens in such situations
      was the principal objective of this work. With this in mind, a series of tests
      were set up to determine the geometry of the emitted beam and to determine the
      response of the sensor to different beam blockage scenarios. The main conclusions
      that were drawn from the results obtained were: (i) in a partial beam blockage
      scenario, the distance value given by the sensor depends more on the blocked
      radiant power than on the blocked surface area; (ii) there is an area that
      influences the measurements obtained that is dependent on the percentage of
      blockage and which ranges from 1.5 to 2.5 m with respect to the foreground
      target/object. If the laser beam impacts on a second target/object located within
      this range, this will affect the measurement given by the sensor. To interpret
      the information obtained from the point clouds provided by the LIDAR sensors,
      such as the volume occupied and the enclosing area, it is necessary to know the
      resolution and the process for obtaining this mesh of points and also to be aware
      of the problem associated with mixed pixels.

PMID- 22163766
TI  - A virtual sensor for online fault detection of multitooth-tools.
AB  - The installation of suitable sensors close to the tool tip on milling centres is
      not possible in industrial environments. It is therefore necessary to design
      virtual sensors for these machines to perform online fault detection in many
      industrial tasks. This paper presents a virtual sensor for online fault detection
      of multitooth tools based on a bayesian classifier. The device that performs this
      task applies mathematical models that function in conjunction with physical
      sensors. Only two experimental variables are collected from the milling centre
      that performs the machining operations: the electrical power consumption of the
      feed drive and the time required for machining each workpiece. The task of
      achieving reliable signals from a milling process is especially complex when
      multitooth tools are used, because each kind of cutting insert in the milling
      centre only works on each workpiece during a certain time window. Great effort
      has gone into designing a robust virtual sensor that can avoid re-calibration due
      to, e.g., maintenance operations. The virtual sensor developed as a result of
      this research is successfully validated under real conditions on a milling centre
      used for the mass production of automobile engine crankshafts. Recognition
      accuracy, calculated with a k-fold cross validation, had on average 0.957 of true
      positives and 0.986 of true negatives. Moreover, measured accuracy was 98%, which
      suggests that the virtual sensor correctly identifies new cases.

PMID- 22163767
TI  - Characteristics of polysilicon wire glucose sensors with a surface modified by
      silica nanoparticles/gamma-APTES nanocomposite.
AB  - This report investigates the sensing characteristics of polysilicon wire (PSW)
      glucose biosensors, including thickness characteristics and line-width effects on
      detection limits, linear range and interference immunity with membranes coated by
      micropipette/spin-coating and focus-ion-beam (FIB) processed capillary atomic
      force-microscopy (C-AFM) tip scan/coating methods. The PSW surface was modified
      with a mixture of 3-aminopropyl-triethoxysilane (gamma-APTES) and
      polydimethylsiloxane (PDMS)-treated hydrophobic fumed silica nanoparticles (NPs).
      We found that the thickness of the gamma-APTES+NPs nonocomposite could be
      controlled well at about 22 nm with small relative standard deviation (RSD) with
      repeated C-AFM tip scan/coatings. The detection limit increased and linear range
      decreased with the line width of the PSW through the tip-coating process.
      Interestingly, the interference immunity ability improves as the line width
      increases. For a 500 nm-wide PSW, the percentage changes of the channel current
      density changes (DeltaJ) caused by acetaminophen (AP) can be kept below 3.5% at
      an ultra-high AP-to-glucose concentration ratio of 600:1. Simulation results
      showed that the line width dependence of interference immunity was strongly
      correlated with the channel electrical field of the PSW biosensor.

PMID- 22163768
TI  - Theory, instrumentation and applications of magnetoelastic resonance sensors: a
      review.
AB  - Thick-film magnetoelastic sensors vibrate mechanically in response to a time
      varying magnetic excitation field. The mechanical vibrations of the
      magnetostrictive magnetoelastic material launch, in turn, a magnetic field by
      which the sensor can be monitored. Magnetic field telemetry enables contact-less,
      remote-query operation that has enabled many practical uses of the sensor
      platform. This paper builds upon a review paper we published in Sensors in 2002
      (Grimes, C.A.; et al. Sensors 2002, 2, 294-313), presenting a comprehensive
      review on the theory, operating principles, instrumentation and key applications
      of magnetoelastic sensing technology.

PMID- 22163769
TI  - Virtual surface characteristics of a tactile display using magneto-rheological
      fluids.
AB  - Virtual surface characteristics of tactile displays are investigated to
      characterize the feeling of human touch for a haptic interface application. In
      order to represent the tactile feeling, a prototype tactile display incorporating
      Magneto-Rheological (MR) fluid has been developed. Tactile display devices
      simulate the finger's skin to feel the sensations of contact such as compliance,
      friction, and topography of the surface. Thus, the tactile display can provide
      information on the surface of an organic tissue to the surgeon in virtual
      reality. In order to investigate the compliance feeling of a human finger's
      touch, normal force responses of a tactile display under various magnetic fields
      have been assessed. Also, shearing friction force responses of the tactile
      display are investigated to simulate the action of finger dragging on the
      surface. Moreover, different matrix arrays of magnetic poles are applied to form
      the virtual surface topography. From the results, different tactile feelings are
      observed according to the applied magnetic field strength as well as the arrays
      of magnetic poles combinations. This research presents a smart tactile display
      technology for virtual surfaces.

PMID- 22163770
TI  - A novel multi-aperture based sun sensor based on a fast multi-point MEANSHIFT
      (FMMS) algorithm.
AB  - With the current increased widespread interest in the development and
      applications of micro/nanosatellites, it was found that we needed to design a
      small high accuracy satellite attitude determination system, because the star
      trackers widely used in large satellites are large and heavy, and therefore not
      suitable for installation on micro/nanosatellites. A Sun sensor + magnetometer is
      proven to be a better alternative, but the conventional sun sensor has low
      accuracy, and cannot meet the requirements of the attitude determination systems
      of micro/nanosatellites, so the development of a small high accuracy sun sensor
      with high reliability is very significant. This paper presents a multi-aperture
      based sun sensor, which is composed of a micro-electro-mechanical system (MEMS)
      mask with 36 apertures and an active pixels sensor (APS) CMOS placed below the
      mask at a certain distance. A novel fast multi-point MEANSHIFT (FMMS) algorithm
      is proposed to improve the accuracy and reliability, the two key performance
      features, of an APS sun sensor. When the sunlight illuminates the sensor, a sun
      spot array image is formed on the APS detector. Then the sun angles can be
      derived by analyzing the aperture image location on the detector via the FMMS
      algorithm. With this system, the centroid accuracy of the sun image can reach
      0.01 pixels, without increasing the weight and power consumption, even when some
      missing apertures and bad pixels appear on the detector due to aging of the
      devices and operation in a harsh space environment, while the pointing accuracy
      of the single-aperture sun sensor using the conventional correlation algorithm is
      only 0.05 pixels.

PMID- 22163771
TI  - Multi-hop routing-based optimization of the number of cluster-heads in wireless
      sensor networks.
AB  - Wireless sensor networks require energy-efficient data transmission because the
      sensor nodes have limited power. A cluster-based routing method is more energy
      efficient than a flat routing method as it can only send specific data for user
      requirements and aggregate similar data by dividing a network into a local
      cluster. However, previous clustering algorithms have some problems in that the
      transmission radius of sensor nodes is not realistic and multi-hop based
      communication is not used both inside and outside local clusters. As energy
      consumption based on clustering is dependent on the number of clusters, we need
      to know how many clusters are best. Thus, we propose an optimal number of cluster
      heads based on multi-hop routing in wireless sensor networks. We observe that a
      local cluster made by a cluster-head influences the energy consumption of sensor
      nodes. We determined an equation for the number of packets to send and relay, and
      calculated the energy consumption of sensor networks using it. Through the
      process of calculating the energy consumption, we can obtain the optimal number
      of cluster-heads in wireless sensor networks.

PMID- 22163772
TI  - Smart query answering for marine sensor data.
AB  - We review existing query answering systems for sensor data. We then propose an
      extended query answering approach termed smart query, specifically for marine
      sensor data. The smart query answering system integrates pattern queries and
      continuous queries. The proposed smart query system considers both streaming data
      and historical data from marine sensor networks. The smart query also uses query
      relaxation technique and semantics from domain knowledge as a recommender system.
      The proposed smart query benefits in building data and information systems for
      marine sensor networks.

PMID- 22163773
TI  - Retraction: Zeng, Y.; Xiong, N.; Park, J.H.; Zheng, G. An emergency-adaptive
      routing scheme for wireless sensor networks for building fire hazard monitoring.
      Sensors 2010, 10, 6128-6148.

PMID- 22163774
TI  - An emergency-adaptive routing scheme for wireless sensor networks for building
      fire hazard monitoring.
AB  - Fire hazard monitoring and evacuation for building environments is a novel
      application area for the deployment of wireless sensor networks. In this context,
      adaptive routing is essential in order to ensure safe and timely data delivery in
      building evacuation and fire fighting resource applications. Existing routing
      mechanisms for wireless sensor networks are not well suited for building fires,
      especially as they do not consider critical and dynamic network scenarios. In
      this paper, an emergency-adaptive, real-time and robust routing protocol is
      presented for emergency situations such as building fire hazard applications. The
      protocol adapts to handle dynamic emergency scenarios and works well with the
      routing hole problem. Theoretical analysis and simulation results indicate that
      our protocol provides a real-time routing mechanism that is well suited for
      dynamic emergency scenarios in building fires when compared with other related
      work.

PMID- 22163775
TI  - ECS: efficient communication scheduling for underwater sensor networks.
AB  - TDMA protocols have attracted a lot of attention for underwater acoustic sensor
      networks (UWSNs), because of the unique characteristics of acoustic signal
      propagation such as great energy consumption in transmission, long propagation
      delay and long communication range. Previous TDMA protocols all allocated
      transmission time to nodes based on discrete time slots. This paper proposes an
      efficient continuous time scheduling TDMA protocol (ECS) for UWSNs, including the
      continuous time based and sender oriented conflict analysis model, the
      transmission moment allocation algorithm and the distributed topology maintenance
      algorithm. Simulation results confirm that ECS improves network throughput by 20%
      on average, compared to existing MAC protocols.

PMID- 22163776
TI  - Nanofluidic refractive-index sensors formed by nanocavity resonators in metals
      without plasmons.
AB  - Nanocavity resonators in metals acting as nanofluidic refractive-index sensors
      were analyzed theoretically. With the illumination of transverse electric
      polarized light, the proposed refractive index sensor structure acts as a pure
      electromagnetic resonator without the excitation of surface plasmons. The
      reflected signal from the nanocavity resonators can be very sensitive to the
      refractive index of the fluids inside the nanocavities due to the enhancement of
      the electric field of the resonant mode inside the cavities. Such a sensor
      configuration can be a useful tool for probing the refractive index change of the
      fluid inside the nanocavities using the spectral, angular or intensity
      interrogation schemes. The wavelength sensitivity of 430 nm/RIU, angular
      sensitivity of 200-1,000 deg/RIU and intensity sensitivity of 25.5 RIU(-1) can be
      achieved in the proposed sensor configuration.

PMID- 22163777
TI  - On the optimal identification of tag sets in time-constrained RFID
      configurations.
AB  - In Radio Frequency Identification facilities the identification delay of a set of
      tags is mainly caused by the random access nature of the reading protocol,
      yielding a random identification time of the set of tags. In this paper, the
      cumulative distribution function of the identification time is evaluated using a
      discrete time Markov chain for single-set time-constrained passive RFID systems,
      namely those ones where a single group of tags is assumed to be in the reading
      area and only for a bounded time (sojourn time) before leaving. In these
      scenarios some tags in a set may leave the reader coverage area unidentified. The
      probability of this event is obtained from the cumulative distribution function
      of the identification time as a function of the sojourn time. This result
      provides a suitable criterion to minimize the probability of losing tags.
      Besides, an identification strategy based on splitting the set of tags in smaller
      subsets is also considered. Results demonstrate that there are optimal splitting
      configurations that reduce the overall identification time while keeping the same
      probability of losing tags.

PMID- 22163778
TI  - Driving down the detection limit in microstructured fiber-based chemical dip
      sensors.
AB  - We present improvements to fluorescence sensing in soft-glass microstructured
      optical fibers that result in significantly improved sensitivity relative to
      previously published results. Concentrations of CdSe quantum dots down to 10 pM
      levels have been demonstrated. We show that the primary limitation to the
      sensitivity of these systems is the intrinsic fluorescence of the glass itself.

PMID- 22163779
TI  - Mapping the Philippines' mangrove forests using Landsat imagery.
AB  - Current, accurate, and reliable information on the areal extent and spatial
      distribution of mangrove forests in the Philippines is limited. Previous
      estimates of mangrove extent do not illustrate the spatial distribution for the
      entire country. This study, part of a global assessment of mangrove dynamics,
      mapped the spatial distribution and areal extent of the Philippines' mangroves
      circa 2000. We used publicly available Landsat data acquired primarily from the
      Global Land Survey to map the total extent and spatial distribution. ISODATA
      clustering, an unsupervised classification technique, was applied to 61 Landsat
      images. Statistical analysis indicates the total area of mangrove forest cover
      was approximately 256,185 hectares circa 2000 with overall classification
      accuracy of 96.6% and a kappa coefficient of 0.926. These results differ
      substantially from most recent estimates of mangrove area in the Philippines. The
      results of this study may assist the decision making processes for rehabilitation
      and conservation efforts that are currently needed to protect and restore the
      Philippines' degraded mangrove forests.

PMID- 22163780
TI  - Application of V2O5/WO3/TiO2 for resistive-type SO2 sensors.
AB  - A study on the application of V(2)O(5)/WO(3)/TiO(2) (VWT) as the sensitive
      material for resistive-type SO(2) sensor was conducted, based on the fact that
      VWT is a well-known catalyst material for good selective catalytic nitrogen oxide
      reduction with a proven excellent durability in exhaust gases. The sensors
      fabricated in this study are planar ones with interdigitated electrodes of Au or
      Pt. The vanadium content of the utilized VWT is 1.5 or 3.0 wt%. The resistance of
      VWT decreases with an increasing SO(2) concentration in the range from 20 ppm to
      5,000 ppm. The best sensor response to SO(2) occurs at 400  degrees C using Au
      electrodes. The sensor response value is independent on the amount of added
      vanadium but dependent on the electrode materials at 400  degrees C. These
      results are discussed and a sensing mechanism is discussed.

PMID- 22163781
TI  - Gas-to-particle conversion in surface discharge nonthermal plasmas and its
      implications for atmospheric chemistry.
AB  - This paper presents some experimental data on gas-to-particle conversion of
      benzene using nonthermal plasma (NTP) technology and discusses the possibility of
      its technical application in atmospheric chemistry. Aerosol measurement using a
      differential mobility analyzer (DMA) revealed that the parts of benzene molecules
      were converted into a nanometer-sized aerosol. Aerosol formation was found to be
      highly related with the missing part in carbon balance. Scanning electron
      microscopy analysis showed that the aerosols formed in synthetic humid air are
      the collection of nanoparticles. The carbonyl band (C=O) was found to be an
      important chemical constituent in the aerosol. The potential of the NTP as an
      accelerated test tool in studying secondary organic aerosol (SOA) formation from
      VOCs will be also addressed.

PMID- 22163782
TI  - Photonic biosensor assays to detect and distinguish subspecies of Francisella
      tularensis.
AB  - The application of photonic biosensor assays to diagnose the category-A select
      agent Francisella tularensis was investigated. Both interferometric and long
      period fiber grating sensing structures were successfully demonstrated; both
      these sensors are capable of detecting the optical changes induced by either
      immunological binding or DNA hybridization. Detection was made possible by the
      attachment of DNA probes or immunoglobulins (IgG) directly to the fiber surface
      via layer-by-layer electrostatic self-assembly. An optical fiber biosensor was
      tested using a standard transmission mode long period fiber grating of length 15
      mm and period 260 MUm, and coated with the IgG fraction of antiserum to F.
      tularensis. The IgG was deposited onto the optical fiber surface in a
      nanostructured film, and the resulting refractive index change was measured using
      spectroscopic ellipsometry. The presence of F. tularensis was detected from the
      decrease of peak wavelength caused by binding of specific antigen. Detection and
      differentiation of F. tularensis subspecies tularensis (type A strain TI0902) and
      subspecies holarctica (type B strain LVS) was further accomplished using a single
      mode multi-cavity fiber Fabry-Perot interferometric sensor. These sensors were
      prepared by depositing seven polymer bilayers onto the fiber tip followed by
      attaching one of two DNA probes: (a) a 101-bp probe from the yhhW gene unique to
      type-A strains, or (b) a 117-bp probe of the lpnA gene, common to both type-A and
      type-B strains. The yhhW probe was reactive with the type-A, but not the type-B
      strain. Probe lpnA was reactive with both type-A and type-B strains. Nanogram
      quantities of the target DNA could be detected, highlighting the sensitivity of
      this method for DNA detection without the use of PCR. The DNA probe reacted with
      100% homologous target DNA, but did not react with sequences containing 2-bp
      mismatches, indicating the high specificity of the assay. These assays will fill
      an important void that exists for rapid, culture-free, and field-compatible
      diagnosis of F. tularensis.

PMID- 22163783
TI  - Estimation of physiological tremor from accelerometers for real-time
      applications.
AB  - Accurate filtering of physiological tremor is extremely important in robotics
      assisted surgical instruments and procedures. This paper focuses on developing
      single stage robust algorithms for accurate tremor filtering with accelerometers
      for real-time applications. Existing methods rely on estimating the tremor under
      the assumption that it has a single dominant frequency. Our time-frequency
      analysis on physiological tremor data revealed that tremor contains multiple
      dominant frequencies over the entire duration rather than a single dominant
      frequency. In this paper, the existing methods for tremor filtering are reviewed
      and two improved algorithms are presented. A comparative study is conducted on
      all the estimation methods with tremor data from microsurgeons and novice
      subjects under different conditions. Our results showed that the new improved
      algorithms performed better than the existing algorithms for tremor estimation. A
      procedure to separate the intended motion/drift from the tremor component is
      formulated.

PMID- 22163784
TI  - Analysis of RFI identification and mitigation in CAROLS radiometer data using a
      hardware spectrum analyser.
AB  - A method to identify and mitigate radio frequency interference (RFI) in microwave
      radiometry based on the use of a spectrum analyzer has been developed. This
      method has been tested with CAROLS L-band airborne radiometer data that are
      strongly corrupted by RFI. RFI is a major limiting factor in passive microwave
      remote sensing interpretation. Although the 1.400-1.427 GHz bandwidth is
      protected, RFI sources close to these frequencies are still capable of corrupting
      radiometric measurements. In order to reduce the detrimental effects of RFI on
      brightness temperature measurements, a new spectrum analyzer has been added to
      the CAROLS radiometer system. A post processing algorithm is proposed, based on
      selective filters within the useful bandwidth divided into sub-bands. Two
      discriminant analyses based on the computation of kurtosis and Euclidian
      distances have been compared evaluated and validated in order to accurately
      separate the RF interference from natural signals.

PMID- 22163785
TI  - Adaptive sampling for learning gaussian processes using mobile sensor networks.
AB  - This paper presents a novel class of self-organizing sensing agents that
      adaptively learn an anisotropic, spatio-temporal gaussian process using noisy
      measurements and move in order to improve the quality of the estimated covariance
      function. This approach is based on a class of anisotropic covariance functions
      of gaussian processes introduced to model a broad range of spatio-temporal
      physical phenomena. The covariance function is assumed to be unknown a priori.
      Hence, it is estimated by the maximum a posteriori probability (MAP) estimator.
      The prediction of the field of interest is then obtained based on the MAP
      estimate of the covariance function. An optimal sampling strategy is proposed to
      minimize the information-theoretic cost function of the Fisher Information
      Matrix. Simulation results demonstrate the effectiveness and the adaptability of
      the proposed scheme.

PMID- 22163786
TI  - Open-gated pH sensor fabricated on an undoped-AlGaN/GaN HEMT structure.
AB  - The sensing responses in aqueous solution of an open-gated pH sensor fabricated
      on an AlGaN/GaN high-electron-mobility-transistor (HEMT) structure are
      investigated. Under air-exposed ambient conditions, the open-gated undoped
      AlGaN/GaN HEMT only shows the presence of a linear current region. This seems to
      show that very low Fermi level pinning by surface states exists in the undoped
      AlGaN/GaN sample. In aqueous solution, typical current-voltage (I-V)
      characteristics with reasonably good gate controllability are observed, showing
      that the potential of the AlGaN surface at the open-gated area is effectively
      controlled via aqueous solution by the Ag/AgCl gate electrode. The open-gated
      undoped AlGaN/GaN HEMT structure is capable of distinguishing pH level in aqueous
      electrolytes and exhibits linear sensitivity, where high sensitivity of 1.9 mA/pH
      or 3.88 mA/mm/pH at drain-source voltage, V(DS) = 5 V is obtained. Due to the
      large leakage current where it increases with the negative gate voltage,
      Nernstian like sensitivity cannot be determined as commonly reported in the
      literature. This large leakage current may be caused by the technical factors
      rather than any characteristics of the devices. Surprisingly, although there are
      some imperfections in the device preparation and measurement, the fabricated
      devices work very well in distinguishing the pH levels. Suppression of current
      leakage by improving the device preparation is likely needed to improve the
      device performance. The fabricated device is expected to be suitable for pH
      sensing applications.

PMID- 22163787
TI  - An efficient transmission power control scheme for temperature variation in
      wireless sensor networks.
AB  - Wireless sensor networks collect data from several nodes dispersed at remote
      sites. Sensor nodes can be installed in harsh environments such as deserts,
      cities, and indoors, where the link quality changes considerably over time.
      Particularly, changes in transmission power may be caused by temperature,
      humidity, and other factors. In order to compensate for link quality changes,
      existing schemes detect the link quality changes between nodes and control
      transmission power through a series of feedback processes, but these approaches
      can cause heavy overhead with the additional control packets needed. In this
      paper, the change of the link quality according to temperature is examined
      through empirical experimentation. A new power control scheme combining both
      temperature-aware link quality compensation and a closed-loop feedback process to
      adapt to link quality changes is proposed. We prove that the proposed scheme
      effectively adapts the transmission power to the changing link quality with less
      control overhead and energy consumption.

PMID- 22163788
TI  - Optimization of sensing and feedback control for vibration/flutter of rotating
      disk by PZT actuators via air coupled pressure.
AB  - In this paper, a feedback control mechanism and its optimization for rotating
      disk vibration/flutter via changes of air-coupled pressure generated using
      piezoelectric patch actuators are studied. A thin disk rotates in an enclosure,
      which is equipped with a feedback control loop consisting of a micro-sensor, a
      signal processor, a power amplifier, and several piezoelectric (PZT) actuator
      patches distributed on the cover of the enclosure. The actuator patches are
      mounted on the inner or the outer surfaces of the enclosure to produce necessary
      control force required through the airflow around the disk. The control mechanism
      for rotating disk flutter using enclosure surfaces bonded with sensors and
      piezoelectric actuators is thoroughly studied through analytical simulations. The
      sensor output is used to determine the amount of input to the actuator for
      controlling the response of the disk in a closed loop configuration. The dynamic
      stability of the disk-enclosure system, together with the feedback control loop,
      is analyzed as a complex eigenvalue problem, which is solved using Galerkin's
      discretization procedure. The results show that the disk flutter can be reduced
      effectively with proper configurations of the control gain and the phase shift
      through the actuations of PZT patches. The effectiveness of different feedback
      control methods in altering system characteristics and system response has been
      investigated. The control capability, in terms of control gain, phase shift, and
      especially the physical configuration of actuator patches, are also evaluated by
      calculating the complex eigenvalues and the maximum displacement produced by the
      actuators. To achieve a optimal control performance, sizes, positions and shapes
      of PZT patches used need to be optimized and such optimization has been achieved
      through numerical simulations.

PMID- 22163789
TI  - Simple random sampling-based probe station selection for fault detection in
      wireless sensor networks.
AB  - Fault detection for wireless sensor networks (WSNs) has been studied intensively
      in recent years. Most existing works statically choose the manager nodes as probe
      stations and probe the network at a fixed frequency. This straightforward
      solution leads however to several deficiencies. Firstly, by only assigning the
      fault detection task to the manager node the whole network is out of balance, and
      this quickly overloads the already heavily burdened manager node, which in turn
      ultimately shortens the lifetime of the whole network. Secondly, probing with a
      fixed frequency often generates too much useless network traffic, which results
      in a waste of the limited network energy. Thirdly, the traditional algorithm for
      choosing a probing node is too complicated to be used in energy-critical wireless
      sensor networks. In this paper, we study the distribution characters of the fault
      nodes in wireless sensor networks, validate the Pareto principle that a small
      number of clusters contain most of the faults. We then present a Simple Random
      Sampling-based algorithm to dynamic choose sensor nodes as probe stations. A
      dynamic adjusting rule for probing frequency is also proposed to reduce the
      number of useless probing packets. The simulation experiments demonstrate that
      the algorithm and adjusting rule we present can effectively prolong the lifetime
      of a wireless sensor network without decreasing the fault detected rate.

PMID- 22163790
TI  - A high temperature capacitive humidity sensor based on mesoporous silica.
AB  - Capacitive sensors are the most commonly used devices for the detection of
      humidity because they are inexpensive and the detection mechanism is very
      specific for humidity. However, especially for industrial processes, there is a
      lack of dielectrics that are stable at high temperature (>200  degrees C) and
      under harsh conditions. We present a capacitive sensor based on mesoporous silica
      as the dielectric in a simple sensor design based on pressed silica pellets.
      Investigation of the structural stability of the porous silica under simulated
      operating conditions as well as the influence of the pellet production will be
      shown. Impedance measurements demonstrate the utility of the sensor at both low
      (90  degrees C) and high (up to 210  degrees C) operating temperatures.

PMID- 22163791
TI  - State derivation of a 12-axis gyroscope-free inertial measurement unit.
AB  - The derivation of linear acceleration, angular acceleration, and angular velocity
      states from a 12-axis gyroscope-free inertial measurement unit that utilizes four
      3-axis accelerometer measurements at four distinct locations is reported.
      Particularly, a new algorithm which derives the angular velocity from its
      quadratic form and derivative form based on the context-based interacting
      multiple model is demonstrated. The performance of the system was evaluated under
      arbitrary 3-dimensional motion.

PMID- 22163792
TI  - Delaunay triangulation as a new coverage measurement method in wireless sensor
      network.
AB  - Sensing and communication coverage are among the most important trade-offs in
      Wireless Sensor Network (WSN) design. A minimum bound of sensing coverage is
      vital in scheduling, target tracking and redeployment phases, as well as
      providing communication coverage. Some methods measure the coverage as a
      percentage value, but detailed information has been missing. Two scenarios with
      equal coverage percentage may not have the same Quality of Coverage (QoC). In
      this paper, we propose a new coverage measurement method using Delaunay
      Triangulation (DT). This can provide the value for all coverage measurement
      tools. Moreover, it categorizes sensors as 'fat', 'healthy' or 'thin' to show the
      dense, optimal and scattered areas. It can also yield the largest empty area of
      sensors in the field. Simulation results show that the proposed DT method can
      achieve accurate coverage information, and provides many tools to compare QoC
      between different scenarios.

PMID- 22163793
TI  - Ontological problem-solving framework for dynamically configuring sensor systems
      and algorithms.
AB  - The deployment of ubiquitous sensor systems and algorithms has led to many
      challenges, such as matching sensor systems to compatible algorithms which are
      capable of satisfying a task. Compounding the challenges is the lack of the
      requisite knowledge models needed to discover sensors and algorithms and to
      subsequently integrate their capabilities to satisfy a specific task. A novel
      ontological problem-solving framework has been designed to match sensors to
      compatible algorithms to form synthesized systems, which are capable of
      satisfying a task and then assigning the synthesized systems to high-level
      missions. The approach designed for the ontological problem-solving framework has
      been instantiated in the context of a persistence surveillance prototype
      environment, which includes profiling sensor systems and algorithms to
      demonstrate proof-of-concept principles. Even though the problem-solving approach
      was instantiated with profiling sensor systems and algorithms, the ontological
      framework may be useful with other heterogeneous sensing-system environments.

PMID- 22163794
TI  - Adaptive marginal median filter for colour images.
AB  - This paper describes a new filter for impulse noise reduction in colour images
      which is aimed at improving the noise reduction capability of the classical
      vector median filter. The filter is inspired by the application of a vector
      marginal median filtering process over a selected group of pixels in each
      filtering window. This selection, which is based on the vector median, along with
      the application of the marginal median operation constitutes an adaptive process
      that leads to a more robust filter design. Also, the proposed method is able to
      process colour images without introducing colour artifacts. Experimental results
      show that the images filtered with the proposed method contain less noisy pixels
      than those obtained through the vector median filter.

PMID- 22163795
TI  - Potentiometric electronic tongue to resolve mixtures of sulfide and perchlorate
      anions.
AB  - This work describes the use of an array of potentiometric sensors and an
      artificial neural network response model to determine perchlorate and sulfide
      ions in polluted waters, by what is known as an electronic tongue. Sensors used
      have been all-solid-state PVC membrane selective electrodes, where their
      ionophores were different metal-phtalocyanine complexes with specific and anion
      generic responses. The study case illustrates the potential use of electronic
      tongues in the quantification of mixtures when interfering effects need to be
      counterbalanced: relative errors in determination of individual ions can be
      decreased typically from 25% to less than 5%, if compared to the use of a single
      proposed ion-selective electrode.

PMID- 22163796
TI  - Gyroscope pivot bearing dimension and surface defect detection.
AB  - Because of the perceived lack of systematic analysis in illumination system
      design processes and a lack of criteria for design methods in vision detection a
      method for the design of a task-oriented illumination system is proposed. After
      detecting the micro-defects of a gyroscope pivot bearing with a high curvature
      glabrous surface and analyzing the characteristics of the surface detection and
      reflection model, a complex illumination system with coaxial and ring lights is
      proposed. The illumination system is then optimized based on the analysis of
      illuminance uniformity of target regions by simulation and grey scale uniformity
      and articulation that are calculated from grey imagery. Currently, in order to
      apply the Pulse Coupled Neural Network (PCNN) method, structural parameters must
      be tested and adjusted repeatedly. Therefore, this paper proposes the use of a
      particle swarm optimization (PSO) algorithm, in which the maximum between cluster
      variance rules is used as fitness function with a linearily reduced inertia
      factor. This algorithm is used to adaptively set PCNN connection coefficients and
      dynamic threshold, which avoids algorithmic precocity and local oscillations. The
      proposed method is used for pivot bearing defect image processing. The
      segmentation results of the maximum entropy and minimum error method and the one
      described in this paper are compared using buffer region matching, and the
      experimental results show that the method of this paper is effective.

PMID- 22163797
TI  - Three realizations and comparison of hardware for piezoresistive tactile sensors.
AB  - Tactile sensors are basically arrays of force sensors that are intended to
      emulate the skin in applications such as assistive robotics. Local electronics
      are usually implemented to reduce errors and interference caused by long wires.
      Realizations based on standard microcontrollers, Programmable Systems on Chip
      (PSoCs) and Field Programmable Gate Arrays (FPGAs) have been proposed by the
      authors for the case of piezoresistive tactile sensors. The solution employing
      FPGAs is especially relevant since their performance is closer to that of
      Application Specific Integrated Circuits (ASICs) than that of the other devices.
      This paper presents an implementation of such an idea for a specific sensor. For
      the purpose of comparison, the circuitry based on the other devices is also made
      for the same sensor. This paper discusses the implementation issues, provides
      details regarding the design of the hardware based on the three devices and
      compares them.

PMID- 22163798
TI  - Optical sensor for diverse organic vapors at ppm concentration ranges.
AB  - A broadly responsive optical organic vapor sensor is described that responds to
      low concentrations of organic vapors without significant interference from water
      vapor. Responses to several classes of organic vapors are highlighted, and trends
      within classes are presented. The relationship between molecular properties
      (vapor pressure, boiling point, polarizability, and refractive index) and sensor
      response are discussed.

PMID- 22163799
TI  - A compatible control algorithm for greenhouse environment control based on MOCC
      strategy.
AB  - Conventional methods used for solving greenhouse environment multi-objective
      conflict control problems lay excessive emphasis on control performance and have
      inadequate consideration for both energy consumption and special requirements for
      plant growth. The resulting solution will cause higher energy cost. However,
      during the long period of work and practice, we find that it may be more
      reasonable to adopt interval or region control objectives instead of point
      control objectives. In this paper, we propose a modified compatible control
      algorithm, and employ Multi-Objective Compatible Control (MOCC) strategy and an
      extant greenhouse model to achieve greenhouse climate control based on feedback
      control architecture. A series of simulation experiments through various
      comparative studies are presented to validate the feasibility of the proposed
      algorithm. The results are encouraging and suggest the energy-saving application
      to real-world engineering problems in greenhouse production. It may be valuable
      and helpful to formulate environmental control strategies, and to achieve high
      control precision and low energy cost for real-world engineering application in
      greenhouse production. Moreover, the proposed approach has also potential to be
      useful for other practical control optimization problems with the features like
      the greenhouse environment control system.

PMID- 22163800
TI  - Contrast-independent biologically inspired motion detection.
AB  - Optic flow, i.e., retinal image movement resulting from ego-motion, is a crucial
      source of information used for obstacle avoidance and course control in flying
      insects. Optic flow analysis may prove promising for mobile robotics although it
      is currently not among the standard techniques. Insects have developed a
      computationally cheap analysis mechanism for image motion. Detailed computational
      models, the so-called elementary motion detectors (EMDs), describe motion
      detection in insects. However, the technical application of EMDs is complicated
      by the strong effect of local pattern contrast on their motion response. Here we
      present augmented versions of an EMD, the (s)cc-EMDs, which normalise their
      responses for contrast and thereby reduce the sensitivity to contrast changes.
      Thus, velocity changes of moving natural images are reflected more reliably in
      the detector response. The (s)cc-EMDs can easily be implemented in hardware and
      software and can be a valuable novel visual motion sensor for mobile robots.

PMID- 22163801
TI  - Signal injection as a fault detection technique.
AB  - Double frequency tests are used for evaluating stator windings and analyzing the
      temperature. Likewise, signal injection on induction machines is used on
      sensorless motor control fields to find out the rotor position. Motor Current
      Signature Analysis (MCSA), which focuses on the spectral analysis of stator
      current, is the most widely used method for identifying faults in induction
      motors. Motor faults such as broken rotor bars, bearing damage and eccentricity
      of the rotor axis can be detected. However, the method presents some problems at
      low speed and low torque, mainly due to the proximity between the frequencies to
      be detected and the small amplitude of the resulting harmonics. This paper
      proposes the injection of an additional voltage into the machine being tested at
      a frequency different from the fundamental one, and then studying the resulting
      harmonics around the new frequencies appearing due to the composition between
      injected and main frequencies.

PMID- 22163802
TI  - A reliable energy-efficient multi-level routing algorithm for wireless sensor
      networks using fuzzy Petri nets.
AB  - A reliable energy-efficient multi-level routing algorithm in wireless sensor
      networks is proposed. The proposed algorithm considers the residual energy,
      number of the neighbors and centrality of each node for cluster formation, which
      is critical for well-balanced energy dissipation of the network. In the
      algorithm, a knowledge-based inference approach using fuzzy Petri nets is
      employed to select cluster heads, and then the fuzzy reasoning mechanism is used
      to compute the degree of reliability in the route sprouting tree from cluster
      heads to the base station. Finally, the most reliable route among the cluster
      heads can be constructed. The algorithm not only balances the energy load of each
      node but also provides global reliability for the whole network. Simulation
      results demonstrate that the proposed algorithm effectively prolongs the network
      lifetime and reduces the energy consumption.

PMID- 22163803
TI  - Implementation of a synchronized oscillator circuit for fast sensing and labeling
      of image objects.
AB  - We present an application-specific integrated circuit (ASIC) CMOS chip that
      implements a synchronized oscillator cellular neural network with a matrix size
      of 32 * 32 for object sensing and labeling in binary images. Networks of
      synchronized oscillators are a recently developed tool for image segmentation and
      analysis. Its parallel network operation is based on a "temporary correlation"
      theory that attempts to describe scene recognition as if performed by the human
      brain. The synchronized oscillations of neuron groups attract a person's
      attention if he or she is focused on a coherent stimulus (image object). For more
      than one perceived stimulus, these synchronized patterns switch in time between
      different neuron groups, thus forming temporal maps that code several features of
      the analyzed scene. In this paper, a new oscillator circuit based on a
      mathematical model is proposed, and the network architecture and chip functional
      blocks are presented and discussed. The proposed chip is implemented in AMIS 0.35
      MUm C035M-D 5M/1P technology. An application of the proposed network chip for the
      segmentation of insulin-producing pancreatic islets in magnetic resonance liver
      images is presented.

PMID- 22163804
TI  - A QoS-guaranteed coverage precedence routing algorithm for wireless sensor
      networks.
AB  - For mission-critical applications of wireless sensor networks (WSNs) involving
      extensive battlefield surveillance, medical healthcare, etc., it is crucial to
      have low-power, new protocols, methodologies and structures for transferring data
      and information in a network with full sensing coverage capability for an
      extended working period. The upmost mission is to ensure that the network is
      fully functional providing reliable transmission of the sensed data without the
      risk of data loss. WSNs have been applied to various types of mission-critical
      applications. Coverage preservation is one of the most essential functions to
      guarantee quality of service (QoS) in WSNs. However, a tradeoff exists between
      sensing coverage and network lifetime due to the limited energy supplies of
      sensor nodes. In this study, we propose a routing protocol to accommodate both
      energy-balance and coverage-preservation for sensor nodes in WSNs. The energy
      consumption for radio transmissions and the residual energy over the network are
      taken into account when the proposed protocol determines an energy-efficient
      route for a packet. The simulation results demonstrate that the proposed protocol
      is able to increase the duration of the on-duty network and provide up to 98.3%
      and 85.7% of extra service time with 100% sensing coverage ratio comparing with
      LEACH and the LEACH-Coverage-U protocols, respectively.

PMID- 22163805
TI  - Resistive oxygen gas sensors for harsh environments.
AB  - Resistive oxygen sensors are an inexpensive alternative to the classical
      potentiometric zirconia oxygen sensor, especially for use in harsh environments
      and at temperatures of several hundred  degrees C or even higher. This device
      oriented paper gives a historical overview on the development of these sensor
      materials. It focuses especially on approaches to obtain a temperature
      independent behavior. It is shown that although in the past 40 years there have
      always been several research groups working concurrently with resistive oxygen
      sensors, novel ideas continue to emerge today with respect to improvements of the
      sensor response time, the temperature dependence, the long-term stability or the
      manufacture of the devices themselves using novel techniques for the sensitive
      films. Materials that are the focus of this review are metal oxides; especially
      titania, titanates, and ceria-based formulations.

PMID- 22163806
TI  - Benchmark for peak detection algorithms in fiber Bragg grating interrogation and
      a new neural network for its performance improvement.
AB  - This paper presents a benchmark for peak detection algorithms employed in fiber
      Bragg grating spectrometric interrogation systems. The accuracy, precision, and
      computational performance of currently used algorithms and those of a new
      proposed artificial neural network algorithm are compared. Centroid and gaussian
      fitting algorithms are shown to have the highest precision but produce systematic
      errors that depend on the FBG refractive index modulation profile. The proposed
      neural network displays relatively good precision with reduced systematic errors
      and improved computational performance when compared to other networks.
      Additionally, suitable algorithms may be chosen with the general guidelines
      presented.

PMID- 22163808
TI  - A survey on routing protocols for large-scale wireless sensor networks.
AB  - With the advances in micro-electronics, wireless sensor devices have been made
      much smaller and more integrated, and large-scale wireless sensor networks (WSNs)
      based the cooperation among the significant amount of nodes have become a hot
      topic. "Large-scale" means mainly large area or high density of a network.
      Accordingly the routing protocols must scale well to the network scope extension
      and node density increases. A sensor node is normally energy-limited and cannot
      be recharged, and thus its energy consumption has a quite significant effect on
      the scalability of the protocol. To the best of our knowledge, currently the
      mainstream methods to solve the energy problem in large-scale WSNs are the
      hierarchical routing protocols. In a hierarchical routing protocol, all the nodes
      are divided into several groups with different assignment levels. The nodes
      within the high level are responsible for data aggregation and management work,
      and the low level nodes for sensing their surroundings and collecting
      information. The hierarchical routing protocols are proved to be more energy
      efficient than flat ones in which all the nodes play the same role, especially in
      terms of the data aggregation and the flooding of the control packets. With focus
      on the hierarchical structure, in this paper we provide an insight into routing
      protocols designed specifically for large-scale WSNs. According to the different
      objectives, the protocols are generally classified based on different criteria
      such as control overhead reduction, energy consumption mitigation and energy
      balance. In order to gain a comprehensive understanding of each protocol, we
      highlight their innovative ideas, describe the underlying principles in detail
      and analyze their advantages and disadvantages. Moreover a comparison of each
      routing protocol is conducted to demonstrate the differences between the
      protocols in terms of message complexity, memory requirements, localization, data
      aggregation, clustering manner and other metrics. Finally some open issues in
      routing protocol design in large-scale wireless sensor networks and conclusions
      are proposed.

PMID- 22163807
TI  - Glucose sensing by time-resolved fluorescence of sol-gel immobilized glucose
      oxidase.
AB  - A monolithic silica gel matrix with entrapped glucose oxidase (GOD) was
      constructed as a bioactive element in an optical biosensor for glucose
      determination. Intrinsic fluorescence of free and immobilised GOD was
      investigated in the visible range in presence of different glucose concentrations
      by time-resolved spectroscopy with time-correlated single-photon counting
      detector. A three-exponential model was used for analysing the fluorescence
      transients. Fractional intensities and mean lifetime were shown to be sensitive
      to the enzymatic reaction and were used for obtaining calibration curve for
      glucose concentration determination. The sensing system proposed achieved high
      resolution (up to 0.17 mM) glucose determination with a detection range from 0.4
      mM to 5 mM.

PMID- 22163809
TI  - On prolonging network lifetime through load-similar node deployment in wireless
      sensor networks.
AB  - This paper is focused on the study of the energy hole problem in the Progressive
      Multi-hop Rotational Clustered (PMRC)-structure, a highly scalable wireless
      sensor network (WSN) architecture. Based on an analysis on the traffic load
      distribution in PMRC-based WSNs, we propose a novel load-similar node
      distribution strategy combined with the Minimum Overlapping Layers (MOL) scheme
      to address the energy hole problem in PMRC-based WSNs. In this strategy, sensor
      nodes are deployed in the network area according to the load distribution. That
      is, more nodes shall be deployed in the range where the average load is higher,
      and then the loads among different areas in the sensor network tend to be
      balanced. Simulation results demonstrate that the load-similar node distribution
      strategy prolongs network lifetime and reduces the average packet latency in
      comparison with existing nonuniform node distribution and uniform node
      distribution strategies. Note that, besides the PMRC structure, the analysis
      model and the proposed load-similar node distribution strategy are also
      applicable to other multi-hop WSN structures.

PMID- 22163811
TI  - Design and development of a run-time monitor for multi-core architectures in
      cloud computing.
AB  - Cloud computing is a new information technology trend that moves computing and
      data away from desktops and portable PCs into large data centers. The basic
      principle of cloud computing is to deliver applications as services over the
      Internet as well as infrastructure. A cloud is a type of parallel and distributed
      system consisting of a collection of inter-connected and virtualized computers
      that are dynamically provisioned and presented as one or more unified computing
      resources. The large-scale distributed applications on a cloud require adaptive
      service-based software, which has the capability of monitoring system status
      changes, analyzing the monitored information, and adapting its service
      configuration while considering tradeoffs among multiple QoS features
      simultaneously. In this paper, we design and develop a Run-Time Monitor (RTM)
      which is a system software to monitor the application behavior at run-time,
      analyze the collected information, and optimize cloud computing resources for
      multi-core architectures. RTM monitors application software through library
      instrumentation as well as underlying hardware through a performance counter
      optimizing its computing configuration based on the analyzed data.

PMID- 22163810
TI  - A review of non-invasive techniques to detect and predict localised muscle
      fatigue.
AB  - Muscle fatigue is an established area of research and various types of muscle
      fatigue have been investigated in order to fully understand the condition. This
      paper gives an overview of the various non-invasive techniques available for use
      in automated fatigue detection, such as mechanomyography, electromyography, near
      infrared spectroscopy and ultrasound for both isometric and non-isometric
      contractions. Various signal analysis methods are compared by illustrating their
      applicability in real-time settings. This paper will be of interest to
      researchers who wish to select the most appropriate methodology for research on
      muscle fatigue detection or prediction, or for the development of devices that
      can be used in, e.g., sports scenarios to improve performance or prevent injury.
      To date, research on localised muscle fatigue focuses mainly on the clinical
      side. There is very little research carried out on the implementation of
      detecting/predicting fatigue using an autonomous system, although recent research
      on automating the process of localised muscle fatigue detection/prediction shows
      promising results.

PMID- 22163812
TI  - Optimal rate allocation in cluster-tree WSNs.
AB  - In this paper, we propose a solution to the problem of guaranteed time slot
      allocation in cluster-tree WSNs. Our design uses the so-called Network Utility
      Maximization (NUM) approach as far as we aim to provide a fair distribution of
      the available resources. From the point of view of implementation, we extend here
      the authors' proposed Coupled-Decompositions Method (CDM) in order to compute the
      NUM problem inside the cluster tree topology and we prove the optimality of this
      new extended version of the method. As a result, we obtain a distributed solution
      that reduces the total amount of signalling information in the network up to a
      factor of 500 with respect to the classical techniques, that is, primal and dual
      decomposition. This is possible because the CDM finds the optimal solution with a
      small number of iterations. Furthermore, when we compare our solution to the
      standard-proposed First Come First Serve (FCFS) policy, we realize that FCFS
      becomes pretty unfair as the traffic load in the network increases and thus, a
      fair allocation of resources can be considered whenever the price to pay in terms
      of signalling and computational complexity is controlled.

PMID- 22163813
TI  - Wireless sensor network-based greenhouse environment monitoring and automatic
      control system for dew condensation prevention.
AB  - Dew condensation on the leaf surface of greenhouse crops can promote diseases
      caused by fungus and bacteria, affecting the growth of the crops. In this paper,
      we present a WSN (Wireless Sensor Network)-based automatic monitoring system to
      prevent dew condensation in a greenhouse environment. The system is composed of
      sensor nodes for collecting data, base nodes for processing collected data, relay
      nodes for driving devices for adjusting the environment inside greenhouse and an
      environment server for data storage and processing. Using the Barenbrug formula
      for calculating the dew point on the leaves, this system is realized to prevent
      dew condensation phenomena on the crop's surface acting as an important element
      for prevention of diseases infections. We also constructed a physical model
      resembling the typical greenhouse in order to verify the performance of our
      system with regard to dew condensation control.

PMID- 22163814
TI  - Auto-configuration protocols in mobile ad hoc networks.
AB  - The TCP/IP protocol allows the different nodes in a network to communicate by
      associating a different IP address to each node. In wired or wireless networks
      with infrastructure, we have a server or node acting as such which correctly
      assigns IP addresses, but in mobile ad hoc networks there is no such centralized
      entity capable of carrying out this function. Therefore, a protocol is needed to
      perform the network configuration automatically and in a dynamic way, which will
      use all nodes in the network (or part thereof) as if they were servers that
      manage IP addresses. This article reviews the major proposed auto-configuration
      protocols for mobile ad hoc networks, with particular emphasis on one of the most
      recent: D2HCP. This work also includes a comparison of auto-configuration
      protocols for mobile ad hoc networks by specifying the most relevant metrics,
      such as a guarantee of uniqueness, overhead, latency, dependency on the routing
      protocol and uniformity.

PMID- 22163815
TI  - Hedonic judgments of chemical compounds are correlated with molecular size.
AB  - Different psychophysical works have reported that, when a wide range of odors is
      assessed, the hedonic dimension is the most salient. Hence, pleasantness is the
      most basic attribute of odor perception. Recent studies suggest that the
      molecular size of a given odorant is positively correlated with its hedonic
      character. This correlation was confirmed in the present study, but further basic
      molecular features affecting pleasantness were identified by means of multiple
      linear regression for the compounds contained in five chemical sets. For three of
      them, hedonic judgments are available in the literature. For a further two
      chemical sets, hedonic scores were estimated from odor character descriptions
      based on numerical profiles. Generally speaking, fairly similar equations were
      obtained for the prediction of hedonic judgments in the five chemical sets, with
      R(2) values ranging from 0.46 to 0.71. The results suggest that larger molecules
      containing oxygen are more likely to be perceived as pleasant, while the opposite
      applies to carboxylic acids and sulfur compounds.

PMID- 22163816
TI  - Fiber optic sensors for structural health monitoring of air platforms.
AB  - Aircraft operators are faced with increasing requirements to extend the service
      life of air platforms beyond their designed life cycles, resulting in heavy
      maintenance and inspection burdens as well as economic pressure. Structural
      health monitoring (SHM) based on advanced sensor technology is potentially a cost
      effective approach to meet operational requirements, and to reduce maintenance
      costs. Fiber optic sensor technology is being developed to provide existing and
      future aircrafts with SHM capability due to its unique superior characteristics.
      This review paper covers the aerospace SHM requirements and an overview of the
      fiber optic sensor technologies. In particular, fiber Bragg grating (FBG) sensor
      technology is evaluated as the most promising tool for load monitoring and damage
      detection, the two critical SHM aspects of air platforms. At last,
      recommendations on the implementation and integration of FBG sensors into an SHM
      system are provided.

PMID- 22163817
TI  - Fabrication of a flexible micro temperature sensor for micro reformer
      applications.
AB  - Micro reformers still face obstacles in minimizing their size, decreasing the
      concentration of CO, conversion efficiency and the feasibility of integrated
      fabrication with fuel cells. By using a micro temperature sensor fabricated on a
      stainless steel-based micro reformer, this work attempts to measure the inner
      temperature and increase the conversion efficiency. Micro temperature sensors on
      a stainless steel substrate are fabricated using micro-electro-mechanical systems
      (MEMS) and then placed separately inside the micro reformer. Micro temperature
      sensors are characterized by their higher accuracy and sensitivity than those of
      a conventional thermocouple. To the best of our knowledge, micro temperature
      sensors have not been embedded before in micro reformers and commercial products,
      therefore, this work presents a novel approach to integrating micro temperature
      sensors in a stainless steel-based micro reformer in order to evaluate inner
      local temperature distributions and enhance reformer performance.

PMID- 22163818
TI  - A very low power MAC (VLPM) protocol for Wireless Body Area Networks.
AB  - Wireless Body Area Networks (WBANs) consist of a limited number of battery
      operated nodes that are used to monitor the vital signs of a patient over long
      periods of time without restricting the patient's movements. They are an easy and
      fast way to diagnose the patient's status and to consult the doctor. Device as
      well as network lifetime are among the most important factors in a WBAN.
      Prolonging the lifetime of the WBAN strongly depends on controlling the energy
      consumption of sensor nodes. To achieve energy efficiency, low duty cycle MAC
      protocols are used, but for medical applications, especially in the case of
      pacemakers where data have time-limited relevance, these protocols increase
      latency which is highly undesirable and leads to system instability. In this
      paper, we propose a low power MAC protocol (VLPM) based on existing wakeup radio
      approaches which reduce energy consumption as well as improving the response time
      of a node. We categorize the traffic into uplink and downlink traffic. The nodes
      are equipped with both a low power wake-up transmitter and receiver. The low
      power wake-up receiver monitors the activity on channel all the time with a very
      low power and keeps the MCU (Micro Controller Unit) along with main radio in
      sleep mode. When a node [BN or BNC (BAN Coordinator)] wants to communicate with
      another node, it uses the low-power radio to send a wakeup packet, which will
      prompt the receiver to power up its primary radio to listen for the message that
      follows shortly. The wake-up packet contains the desired node's ID along with
      some other information to let the targeted node to wake-up and take part in
      communication and let all other nodes to go to sleep mode quickly. The VLPM
      protocol is proposed for applications having low traffic conditions. For high
      traffic rates, optimization is needed. Analytical results show that the proposed
      protocol outperforms both synchronized and unsynchronized MAC protocols like T
      MAC, SCP-MAC, B-MAC and X-MAC in terms of energy consumption and response time.

PMID- 22163819
TI  - Implementation of the Rauch-Tung-Striebel smoother for sensor compatibility
      correction of a fixed-wing unmanned air vehicle.
AB  - This paper presents a complete procedure for sensor compatibility correction of a
      fixed-wing Unmanned Air Vehicle (UAV). The sensors consist of a differential air
      pressure transducer for airspeed measurement, two airdata vanes installed on an
      airdata probe for angle of attack (AoA) and angle of sideslip (AoS) measurement,
      and an Attitude and Heading Reference System (AHRS) that provides attitude
      angles, angular rates, and acceleration. The procedure is mainly based on a two
      pass algorithm called the Rauch-Tung-Striebel (RTS) smoother, which consists of a
      forward pass Extended Kalman Filter (EKF) and a backward recursion smoother. On
      top of that, this paper proposes the implementation of the Wiener Type Filter
      prior to the RTS in order to avoid the complicated process noise covariance
      matrix estimation. Furthermore, an easy to implement airdata measurement noise
      variance estimation method is introduced. The method estimates the airdata and
      subsequently the noise variances using the ground speed and ascent rate provided
      by the Global Positioning System (GPS). It incorporates the idea of data
      regionality by assuming that some sort of statistical relation exists between
      nearby data points. Root mean square deviation (RMSD) is being employed to
      justify the sensor compatibility. The result shows that the presented procedure
      is easy to implement and it improves the UAV sensor data compatibility
      significantly.

PMID- 22163820
TI  - Hyperspectral and chlorophyll fluorescence imaging to analyse the impact of
      Fusarium culmorum on the photosynthetic integrity of infected wheat ears.
AB  - Head blight on wheat, caused by Fusarium spp., is a serious problem for both
      farmers and food production due to the concomitant production of highly toxic
      mycotoxins in infected cereals. For selective mycotoxin analyses, information
      about the on-field status of infestation would be helpful. Early symptom
      detection directly on ears, together with the corresponding geographic position,
      would be important for selective harvesting. Hence, the capabilities of various
      digital imaging methods to detect head blight disease on winter wheat were
      tested. Time series of images of healthy and artificially Fusarium-infected ears
      were recorded with a laboratory hyperspectral imaging system (wavelength range:
      400 nm to 1,000 nm). Disease-specific spectral signatures were evaluated with an
      imaging software. Applying the 'Spectral Angle Mapper' method, healthy and
      infected ear tissue could be clearly classified. Simultaneously, chlorophyll
      fluorescence imaging of healthy and infected ears, and visual rating of the
      severity of disease was performed. Between six and eleven days after artificial
      inoculation, photosynthetic efficiency of infected compared to healthy ears
      decreased. The severity of disease highly correlated with photosynthetic
      efficiency. Above an infection limit of 5% severity of disease, chlorophyll
      fluorescence imaging reliably recognised infected ears. With this technique,
      differentiation of the severity of disease was successful in steps of 10%.
      Depending on the quality of chosen regions of interests, hyperspectral imaging
      readily detects head blight 7 d after inoculation up to a severity of disease of
      50%. After beginning of ripening, healthy and diseased ears were hardly
      distinguishable with the evaluated methods.

PMID- 22163821
TI  - Tapered optical fiber sensor for label-free detection of biomolecules.
AB  - This paper presents a fast, highly sensitive and low-cost tapered optical fiber
      biosensor that enables the label-free detection of biomolecules. The sensor takes
      advantage of the interference effect between the fiber's first two propagation
      modes along the taper waist region. The biomolecules bonded on the taper surface
      were determined by demodulating the transmission spectrum phase shift. Because of
      the sharp spectrum fringe signals, as well as a relatively long biomolecule
      testing region, the sensor displayed a fast response and was highly sensitive. To
      better understand the influence of various biomolecules on the sensor, a
      numerical simulation that varied biolayer parameters such as thickness and
      refractive index was performed. The results showed that the spectrum fringe shift
      was obvious to be measured even when the biolayer was only nanometers thick. A
      microchannel chip was designed and fabricated for the protection of the sensor
      and biotesting. Microelectromechanical systems (MEMS) fabrication techniques were
      used to precisely control the profile and depth of the microchannel on the
      silicon chip with an accuracy of 2 MUm. A tapered optical fiber biosensor was
      fabricated and evaluated with an Immune globulin G (IgG) antibody-antigen pair.

PMID- 22163822
TI  - An approach to an inhibition electronic tongue to detect on-line organophosphorus
      insecticides using a computer controlled multi-commuted flow system.
AB  - An approach to an inhibition bioelectronic tongue is presented. The work is
      focused on development of an automated flow system to carry out experimental
      assays, a custom potentiostat to measure the response from an enzymatic
      biosensor, and an inhibition protocol which allows on-line detections. A Multi
      commuted Flow Analysis system (MCFA) was selected and developed to carry out
      assays with an improved inhibition method to detect the insecticides chlorpyrifos
      oxon (CPO), chlorfenvinfos (CFV) and azinphos methyl-oxon (AZMO). The system
      manifold comprised a peristaltic pump, a set of seven electronic valves
      controlled by a personal computer electronic interface and software based on
      LabView(r) to control the sample dilutions into the cell. The inhibition method
      consists in the injection of the insecticide when the enzyme activity has reached
      the plateau of the current; with this method the incubation time is avoided. A
      potentiostat was developed to measure the response from the enzymatic biosensor.
      Low limits of detection of 10 nM for CPO, CFV, and AZMO were achieved.

PMID- 22163823
TI  - Three-dimensional modeling of tea-shoots using images and models.
AB  - In this paper, a method for three-dimensional modeling of tea-shoots with images
      and calculation models is introduced. The process is as follows: the tea shoots
      are photographed with a camera, color space conversion is conducted, using an
      improved algorithm that is based on color and regional growth to divide the tea
      shoots in the images, and the edges of the tea shoots extracted with the help of
      edge detection; after that, using the divided tea-shoot images, the three
      dimensional coordinates of the tea shoots are worked out and the feature
      parameters extracted, matching and calculation conducted according to the model
      database, and finally the three-dimensional modeling of tea-shoots is completed.
      According to the experimental results, this method can avoid a lot of
      calculations and has better visual effects and, moreover, performs better in
      recovering the three-dimensional information of the tea shoots, thereby providing
      a new method for monitoring the growth of and non-destructive testing of tea
      shoots.

PMID- 22163824
TI  - Gain-scheduled complementary filter design for a MEMS based attitude and heading
      reference system.
AB  - This paper describes a robust and simple algorithm for an attitude and heading
      reference system (AHRS) based on low-cost MEMS inertial and magnetic sensors. The
      proposed approach relies on a gain-scheduled complementary filter, augmented by
      an acceleration-based switching architecture to yield robust performance, even
      when the vehicle is subject to strong accelerations. Experimental results are
      provided for a road captive test during which the vehicle dynamics are in high
      acceleration mode and the performance of the proposed filter is evaluated against
      the output from a conventional linear complementary filter.

PMID- 22163825
TI  - Estimation of the distribution of Tabebuia guayacan (Bignoniaceae) using high
      resolution remote sensing imagery.
AB  - Species identification and characterization in tropical environments is an
      emerging field in tropical remote sensing. Significant efforts are currently
      aimed at the detection of tree species, of levels of forest successional stages,
      and the extent of liana occurrence at the top of canopies. In this paper we
      describe our use of high resolution imagery from the Quickbird Satellite to
      estimate the flowering population of Tabebuia guayacan trees at Barro Colorado
      Island (BCI), in Panama. The imagery was acquired on 29 April 2002 and 21 March
      2004. Spectral Angle Mapping via a One-Class Support Vector machine was used to
      detect the presence of 422 and 557 flowering tress in the April 2002 and March
      2004 imagery. Of these, 273 flowering trees are common to both dates. This study
      presents a new perspective on the effectiveness of high resolution remote sensing
      for monitoring a phenological response and its use as a tool for potential
      conservation and management of natural resources in tropical environments.

PMID- 22163826
TI  - An enhanced reservation-based MAC protocol for IEEE 802.15.4 networks.
AB  - The IEEE 802.15.4 Medium Access Control (MAC) protocol is an enabling standard
      for wireless sensor networks. In order to support applications requiring
      dedicated bandwidth or bounded delay, it provides a reservation-based scheme
      named Guaranteed Time Slot (GTS). However, the GTS scheme presents some
      drawbacks, such as inefficient bandwidth utilization and support to a maximum of
      only seven devices. This paper presents eLPRT (enhanced Low Power Real Time), a
      new reservation-based MAC protocol that introduces several performance enhancing
      features in comparison to the GTS scheme. This MAC protocol builds on top of LPRT
      (Low Power Real Time) and includes various mechanisms designed to increase data
      transmission reliability against channel errors, improve bandwidth utilization
      and increase the number of supported devices. A motion capture system based on
      inertial and magnetic sensors has been used to validate the protocol. The
      effectiveness of the performance enhancements introduced by each of the new
      features is demonstrated through the provision of both simulation and
      experimental results.

PMID- 22163827
TI  - From Sensor to Observation Web with environmental enablers in the Future
      Internet.
AB  - This paper outlines the grand challenges in global sustainability research and
      the objectives of the FP7 Future Internet PPP program within the Digital Agenda
      for Europe. Large user communities are generating significant amounts of valuable
      environmental observations at local and regional scales using the devices and
      services of the Future Internet. These communities' environmental observations
      represent a wealth of information which is currently hardly used or used only in
      isolation and therefore in need of integration with other information sources.
      Indeed, this very integration will lead to a paradigm shift from a mere Sensor
      Web to an Observation Web with semantically enriched content emanating from
      sensors, environmental simulations and citizens. The paper also describes the
      research challenges to realize the Observation Web and the associated
      environmental enablers for the Future Internet. Such an environmental enabler
      could for instance be an electronic sensing device, a web-service application, or
      even a social networking group affording or facilitating the capability of the
      Future Internet applications to consume, produce, and use environmental
      observations in cross-domain applications. The term "envirofied" Future Internet
      is coined to describe this overall target that forms a cornerstone of work in the
      Environmental Usage Area within the Future Internet PPP program. Relevant trends
      described in the paper are the usage of ubiquitous sensors (anywhere), the
      provision and generation of information by citizens, and the convergence of real
      and virtual realities to convey understanding of environmental observations. The
      paper addresses the technical challenges in the Environmental Usage Area and the
      need for designing multi-style service oriented architecture. Key topics are the
      mapping of requirements to capabilities, providing scalability and robustness
      with implementing context aware information retrieval. Another essential research
      topic is handling data fusion and model based computation, and the related
      propagation of information uncertainty. Approaches to security, standardization
      and harmonization, all essential for sustainable solutions, are summarized from
      the perspective of the Environmental Usage Area. The paper concludes with an
      overview of emerging, high impact applications in the environmental areas
      concerning land ecosystems (biodiversity), air quality (atmospheric conditions)
      and water ecosystems (marine asset management).

PMID- 22163828
TI  - Multi-hop localization algorithm based on grid-scanning for wireless sensor
      networks.
AB  - For large-scale wireless sensor networks (WSNs) with a minority of anchor nodes,
      multi-hop localization is a popular scheme for determining the geographical
      positions of the normal nodes. However, in practice existing multi-hop
      localization methods suffer from various kinds of problems, such as poor
      adaptability to irregular topology, high computational complexity, low
      positioning accuracy, etc. To address these issues in this paper, we propose a
      novel Multi-hop Localization algorithm based on Grid-Scanning (MLGS). First, the
      factors that influence the multi-hop distance estimation are studied and a more
      realistic multi-hop localization model is constructed. Then, the feasible regions
      of the normal nodes are determined according to the intersection of bounding
      square rings. Finally, a verifiably good approximation scheme based on grid
      scanning is developed to estimate the coordinates of the normal nodes.
      Additionally, the positioning accuracy of the normal nodes can be improved
      through neighbors' collaboration. Extensive simulations are performed in
      isotropic and anisotropic networks. The comparisons with some typical algorithms
      of node localization confirm the effectiveness and efficiency of our algorithm.

PMID- 22163829
TI  - Time-frequency analyses of tide-gauge sensor data.
AB  - The real world phenomena being observed by sensors are generally non-stationary
      in nature. The classical linear techniques for analysis and modeling natural time
      series observations are inefficient and should be replaced by non-linear
      techniques of whose theoretical aspects and performances are varied. In this
      manner adopting the most appropriate technique and strategy is essential in
      evaluating sensors' data. In this study, two different time-series analysis
      approaches, namely least squares spectral analysis (LSSA) and wavelet analysis
      (continuous wavelet transform, cross wavelet transform and wavelet coherence
      algorithms as extensions of wavelet analysis), are applied to sea-level
      observations recorded by tide-gauge sensors, and the advantages and drawbacks of
      these methods are reviewed. The analyses were carried out using sea-level
      observations recorded at the Antalya-II and Erdek tide-gauge stations of the
      Turkish National Sea-Level Monitoring System. In the analyses, the useful
      information hidden in the noisy signals was detected, and the common features
      between the two sea-level time series were clarified. The tide-gauge records have
      data gaps in time because of issues such as instrumental shortcomings and power
      outages. Concerning the difficulties of the time-frequency analysis of data with
      voids, the sea-level observations were preprocessed, and the missing parts were
      predicted using the neural network method prior to the analysis. In conclusion
      the merits and limitations of the techniques in evaluating non-stationary
      observations by means of tide-gauge sensors records were documented and an
      analysis strategy for the sequential sensors observations was presented.

PMID- 22163830
TI  - Novel mechano-luminescent sensors based on piezoelectric/electroluminescent
      composites.
AB  - A high-sensitivity mechano-luminescent sensor was fabricated on the basis of
      piezoelectric/electroluminescent composites. The working principle of this
      mechano-luminescent sensor was elucidated by analyzing the relationship between
      the piezoelectric-induced charges and the electroluminescent effects. When a
      stress is applied on the piezoelectric layer, electrical charges will be induced
      at both the top and bottom sides of the piezoelectric layer. The induced
      electrical charges will lead to a light output from the electroluminescent layer,
      thus producing a mechano-luminescence effect. By increasing the vibration
      strength or frequency applied, the mechano-luminescence output can be obviously
      enhanced. Mechano-luminescence sensors have potential in smart stress-to-light
      devices, such as foot-stress-distribution-diagnosis systems and dynamic-load
      monitors for bridge hanging cables.

PMID- 22163831
TI  - Metallo-graphene nanocomposite electrocatalytic platform for the determination of
      toxic metal ions.
AB  - A Nafion-Graphene (Nafion-G) nanocomposite solution in combination with an in
      situ plated mercury film electrode was used as a highly sensitive electrochemical
      platform for the determination of Zn(2+), Cd(2+), Pb(2+) and Cu(2+) in 0.1 M
      acetate buffer (pH 4.6) by square-wave anodic stripping voltammetry (SWASV).
      Various operational parameters such as deposition potential, deposition time and
      electrode rotation speed were optimized. The Nafion-G nanocomposite sensing
      platform exhibited improved sensitivity for metal ion detection, in addition to
      well defined, reproducible and sharp stripping signals. The linear calibration
      curves ranged from 1 MUg L(-1) to 7 MUg L(-1) for individual analysis. The
      detection limits (3sigma blank/slope) obtained were 0.07 MUg L(-1) for Pb(2+),
      Zn(2+) and Cu(2+) and 0.08 MUg L(-1) for Cd(2+) at a deposition time of 120 s.
      For practical applications recovery studies was done by spiking test samples with
      known concentrations and comparing the results with inductively coupled plasma
      mass spectrometry (ICP-MS) analyses. This was followed by real sample analysis.

PMID- 22163832
TI  - An intelligent tool for activity data collection.
AB  - Activity recognition systems using simple and ubiquitous sensors require a large
      variety of real-world sensor data for not only evaluating their performance but
      also training the systems for better functioning. However, a tremendous amount of
      effort is required to setup an environment for collecting such data. For example,
      expertise and resources are needed to design and install the sensors,
      controllers, network components, and middleware just to perform basic data
      collections. It is therefore desirable to have a data collection method that is
      inexpensive, flexible, user-friendly, and capable of providing large and diverse
      activity datasets. In this paper, we propose an intelligent activity data
      collection tool which has the ability to provide such datasets inexpensively
      without physically deploying the testbeds. It can be used as an inexpensive and
      alternative technique to collect human activity data. The tool provides a set of
      web interfaces to create a web-based activity data collection environment. It
      also provides a web-based experience sampling tool to take the user's activity
      input. The tool generates an activity log using its activity knowledge and the
      user-given inputs. The activity knowledge is mined from the web. We have
      performed two experiments to validate the tool's performance in producing
      reliable datasets.

PMID- 22163833
TI  - Intelligent method for diagnosing structural faults of rotating machinery using
      ant colony optimization.
AB  - Structural faults, such as unbalance, misalignment and looseness, etc., often
      occur in the shafts of rotating machinery. These faults may cause serious machine
      accidents and lead to great production losses. This paper proposes an intelligent
      method for diagnosing structural faults of rotating machinery using ant colony
      optimization (ACO) and relative ratio symptom parameters (RRSPs) in order to
      detect faults and distinguish fault types at an early stage. New symptom
      parameters called "relative ratio symptom parameters" are defined for reflecting
      the features of vibration signals measured in each state. Synthetic detection
      index (SDI) using statistical theory has also been defined to evaluate the
      applicability of the RRSPs. The SDI can be used to indicate the fitness of a RRSP
      for ACO. Lastly, this paper also compares the proposed method with the
      conventional neural networks (NN) method. Practical examples of fault diagnosis
      for a centrifugal fan are provided to verify the effectiveness of the proposed
      method. The verification results show that the structural faults often occurring
      in the centrifugal fan, such as unbalance, misalignment and looseness states are
      effectively identified by the proposed method, while these faults are difficult
      to detect using conventional neural networks.

PMID- 22163834
TI  - Surface plasmon resonance based biosensors for exploring the influence of
      alkaloids on aggregation of amyloid-beta peptide.
AB  - The main objective of the presented study was the development of a simple
      analytical tool for exploring the influence of naturally occurring compounds on
      the aggregation of amyloid-beta peptide (Abeta(40)) in order to find potential
      anti-neurodegenerative drugs. The gold discs used for surface plasmon resonance
      (SPR) measurements were modified with thioaliphatic acid. The surface
      functionalized with carboxylic groups was used for covalent attaching of
      Abeta(40) probe by creation of amide bonds in the presence of EDC/NHS. The
      modified SPR gold discs were used for exploring the Abeta(40) aggregation process
      in the presence of selected alkaloids: arecoline hydrobromide, pseudopelletierine
      hydrochloride, trigonelline hydrochloride and alpha-lobeline hydrochloride. The
      obtained results were discussed with other parameters which govern the phenomenon
      studied such as lipophilicity/hydrophilicy and Abeta(40)-alkaloid association
      constants.

PMID- 22163835
TI  - Detection, composition and treatment of volatile organic compounds from waste
      treatment plants.
AB  - Environmental policies at the European and global level support the diversion of
      wastes from landfills for their treatment in different facilities. Organic waste
      is mainly treated or valorized through composting, anaerobic digestion or a
      combination of both treatments. Thus, there are an increasing number of waste
      treatment plants using this type of biological treatment. During waste handling
      and biological decomposition steps a number of gaseous compounds are generated or
      removed from the organic matrix and emitted. Different families of Volatile
      Organic Compounds (VOC) can be found in these emissions. Many of these compounds
      are also sources of odor nuisance. In fact, odors are the main source of
      complaints and social impacts of any waste treatment plant. This work presents a
      summary of the main types of VOC emitted in organic waste treatment facilities
      and the methods used to detect and quantify these compounds, together with the
      treatment methods applied to gaseous emissions commonly used in composting and
      anaerobic digestion facilities.

PMID- 22163836
TI  - Bromocresol green/mesoporous silica adsorbent for ammonia gas sensing via an
      optical sensing instrument.
AB  - A meso-structured Al-MCM-41 material was impregnated with bromocresol green (BG)
      dye and then incorporated into a UV-Vis DRA spectroscopic instrument for the
      online detection of ammonia gas. The absorption response of the Al-MCM-41/BG
      ammonia sensing material was very sensitive at the optical absorption wavelength
      of 630 nm. A high linear correlation was achieved for ppmv and sub-ppmv levels of
      ammonia gas. The response time for the quantitative detection of ammonia gas
      concentrations ranging from 0.25 to 2.0 ppmv was only a few minutes. The lower
      detection limit achieved was 0.185 ppmv. The color change process was fully
      reversible during tens of cycling tests. These features together make this
      mesoporous Al-MCM-41 material very promising for optical sensing applications.

PMID- 22163837
TI  - Determination of moisture content in oil palm fruits using a five-port
      reflectometer.
AB  - This paper presents the development of a PC-based microwave five-port
      reflectometer for the determination of moisture content in oil palm fruits. The
      reflectometer was designed to measure both the magnitude and phase of the
      reflection coefficient of any passive microwave device. The stand-alone
      reflectometer consists of a PC, a microwave source, diode detectors and an analog
      to digital converter. All the measurement and data acquisition were done using
      Agilent VEE graphical programming software. The relectometer can be used with any
      reflection based microwave sensor. In this work, the application of the
      reflectometer as a useful instrument to determine the moisture content in oil
      palm fruits using monopole and coaxial sensors was demonstrated. Calibration
      equations between reflection coefficients and moisture content have been
      established for both sensors. The equation based on phase measurement of monopole
      sensor was found to be accurate within 5% in predicting moisture content in the
      fruits when compared to the conventional oven drying method.

PMID- 22163838
TI  - A new approach to visual-based sensory system for navigation into orange groves.
AB  - One of the most important parts of an autonomous robot is to establish the path
      by which it should navigate in order to successfully achieve its goals. In the
      case of agricultural robotics, a procedure that determines this desired path can
      be useful. In this paper, a new virtual sensor is introduced in order to classify
      the elements of an orange grove. This proposed sensor will be based on a color
      CCD camera with auto iris lens which is in charge of doing the captures of the
      real environment and an ensemble of neural networks which processes the capture
      and differentiates each element of the image. Then, the Hough's transform and
      other operations will be applied in order to extract the desired path from the
      classification performed by the virtual sensory system. With this approach, the
      robotic system can correct its deviation with respect to the desired path. The
      results show that the sensory system properly classifies the elements of the
      grove and can set trajectory of the robot.

PMID- 22163839
TI  - A distance-aware replica adaptive data gathering protocol for Delay Tolerant
      Mobile Sensor Networks.
AB  - In Delay Tolerant Mobile Sensor Networks (DTMSNs) that have the inherent features
      of intermitted connectivity and frequently changing network topology it is
      reasonable to utilize multi-replica schemes to improve the data gathering
      performance. However, most existing multi-replica approaches inject a large
      amount of message copies into the network to increase the probability of message
      delivery, which may drain each mobile node's limited battery supply faster and
      result in too much contention for the restricted resources of the DTMSN, so a
      proper data gathering scheme needs a trade off between the number of replica
      messages and network performance. In this paper, we propose a new data gathering
      protocol called DRADG (for Distance-aware Replica Adaptive Data Gathering
      protocol), which economizes network resource consumption through making use of a
      self-adapting algorithm to cut down the number of redundant replicas of messages,
      and achieves a good network performance by leveraging the delivery probabilities
      of the mobile sensors as main routing metrics. Simulation results have shown that
      the proposed DRADG protocol achieves comparable or higher message delivery ratios
      at the cost of the much lower transmission overhead than several current DTMSN
      data gathering schemes.

PMID- 22163840
TI  - A lightweight data integrity scheme for sensor networks.
AB  - Limited energy is the most critical constraint that limits the capabilities of
      wireless sensor networks (WSNs). Most sensors operate on batteries with limited
      power. Battery recharging or replacement may be impossible. Security mechanisms
      that are based on public key cryptographic algorithms such as RSA and digital
      signatures are prohibitively expensive in terms of energy consumption and storage
      requirements, and thus unsuitable for WSN applications. This paper proposes a new
      fragile watermarking technique to detect unauthorized alterations in WSN data
      streams. We propose the FWC-D scheme, which uses group delimiters to keep the
      sender and receivers synchronized and help them to avoid ambiguity in the event
      of data insertion or deletion. The watermark, which is computed using a hash
      function, is stored in the previous group in a linked-list fashion to ensure data
      freshness and mitigate replay attacks, FWC-D generates a serial number SN that is
      attached to each group to help the receiver determines how many group insertions
      or deletions occurred. Detailed security analysis that compares the proposed FWC
      D scheme with SGW, one of the latest integrity schemes for WSNs, shows that FWC-D
      is more robust than SGW. Simulation results further show that the proposed scheme
      is much faster than SGW.

PMID- 22163841
TI  - Bioinspired principles for large-scale networked sensor systems: an overview.
AB  - Biology has often been used as a source of inspiration in computer science and
      engineering. Bioinspired principles have found their way into network node design
      and research due to the appealing analogies between biological systems and large
      networks of small sensors. This paper provides an overview of bioinspired
      principles and methods such as swarm intelligence, natural time synchronization,
      artificial immune system and intercellular information exchange applicable for
      sensor network design. Bioinspired principles and methods are discussed in the
      context of routing, clustering, time synchronization, optimal node deployment,
      localization and security and privacy.

PMID- 22163842
TI  - Recent progress in Brillouin scattering based fiber sensors.
AB  - Brillouin scattering in optical fiber describes the interaction of an electro
      magnetic field (photon) with a characteristic density variation of the fiber.
      When the electric field amplitude of an optical beam (so-called pump wave), and
      another wave is introduced at the downshifted Brillouin frequency (namely Stokes
      wave), the beating between the pump and Stokes waves creates a modified density
      change via the electrostriction effect, resulting in so-called the stimulated
      Brillouin scattering. The density variation is associated with a mechanical
      acoustic wave; and it may be affected by local temperature, strain, and vibration
      which induce changes in the fiber effective refractive index and sound velocity.
      Through the measurement of the static or dynamic changes in Brillouin frequency
      along the fiber one can realize a distributed fiber sensor for local temperature,
      strain and vibration over tens or hundreds of kilometers. This paper reviews the
      progress on improving sensing performance parameters like spatial resolution,
      sensing length limitation and simultaneous temperature and strain measurement.
      These kinds of sensors can be used in civil structural monitoring of pipelines,
      bridges, dams, and railroads for disaster prevention. Analogous to the static
      Bragg grating, one can write a moving Brillouin grating in fibers, with the
      lifetime of the acoustic wave. The length of the Brillouin grating can be
      controlled by the writing pulses at any position in fibers. Such gratings can be
      used to measure changes in birefringence, which is an important parameter in
      fiber communications. Applications for this kind of sensor can be found in
      aerospace, material processing and fine structures.

PMID- 22163843
TI  - Can infrared spectroscopy be used to measure change in potassium nitrate
      concentration as a proxy for soil particle movement?
AB  - Displacement of soil particles caused by erosion influences soil condition and
      fertility. To date, the cesium 137 isotope ((137)Cs) technique is most commonly
      used for soil particle tracing. However when large areas are considered, the
      expensive soil sampling and analysis present an obstacle. Infrared spectral
      measurements would provide a solution, however the small concentrations of the
      isotope do not influence the spectral signal sufficiently. Potassium (K) has
      similar electrical, chemical and physical properties as Cs. Our hypothesis is
      that it can be used as possible replacement in soil particle tracing. Soils
      differing in texture were sampled for the study. Laboratory soil chemical
      analyses and spectral sensitivity analyses were carried out to identify the
      wavelength range related to K concentration. Different concentrations of K
      fertilizer were added to soils with varying texture properties in order to
      establish spectral characteristics of the absorption feature associated with the
      element. Changes in position of absorption feature center were observed at
      wavelengths between 2,450 and 2,470 nm, depending on the amount of fertilizer
      applied. Other absorption feature parameters (absorption band depth, width and
      area) were also found to change with K concentration with coefficient of
      determination between 0.85 and 0.99. Tracing soil particles using K fertilizer
      and infrared spectral response is considered suitable for soils with sandy and
      sandy silt texture. It is a new approach that can potentially grow to a technique
      for rapid monitoring of soil particle movement over large areas.

PMID- 22163844
TI  - Applying Rprop neural network for the prediction of the mobile station location.
AB  - Wireless location is the function used to determine the mobile station (MS)
      location in a wireless cellular communications system. When it is very hard for
      the surrounding base stations (BSs) to detect a MS or the measurements contain
      large errors in non-line-of-sight (NLOS) environments, then one need to integrate
      all available heterogeneous measurements to increase the location accuracy. In
      this paper we propose a novel algorithm that combines both time of arrival (TOA)
      and angle of arrival (AOA) measurements to estimate the MS in NLOS environments.
      The proposed algorithm utilizes the intersections of two circles and two lines,
      based on the most resilient back-propagation (Rprop) neural network learning
      technique, to give location estimation of the MS. The traditional Taylor series
      algorithm (TSA) and the hybrid lines of position algorithm (HLOP) have
      convergence problems, and even if the measurements are fairly accurate, the
      performance of these algorithms depends highly on the relative position of the MS
      and BSs. Different NLOS models were used to evaluate the proposed methods.
      Numerical results demonstrate that the proposed algorithms can not only preserve
      the convergence solution, but obtain precise location estimations, even in severe
      NLOS conditions, particularly when the geometric relationship of the BSs relative
      to the MS is poor.

PMID- 22163845
TI  - SMS-based medical diagnostic telemetry data transmission protocol for medical
      sensors.
AB  - People with special medical monitoring needs can, these days, be sent home and
      remotely monitored through the use of data logging medical sensors and a
      transmission base-station. While this can improve quality of life by allowing the
      patient to spend most of their time at home, most current technologies rely on
      hardwired landline technology or expensive mobile data transmissions to transmit
      data to a medical facility. The aim of this paper is to investigate and develop
      an approach to increase the freedom of a monitored patient and decrease costs by
      utilising mobile technologies and SMS messaging to transmit data from patient to
      medico. To this end, we evaluated the capabilities of SMS and propose a generic
      communications protocol which can work within the constraints of the SMS format,
      but provide the necessary redundancy and robustness to be used for the
      transmission of non-critical medical telemetry from data logging medical sensors.

PMID- 22163846
TI  - Tightly coupled low cost 3D RISS/GPS integration using a mixture particle filter
      for vehicular navigation.
AB  - Satellite navigation systems such as the global positioning system (GPS) are
      currently the most common technique used for land vehicle positioning. However,
      in GPS-denied environments, there is an interruption in the positioning
      information. Low-cost micro-electro mechanical system (MEMS)-based inertial
      sensors can be integrated with GPS and enhance the performance in denied GPS
      environments. The traditional technique for this integration problem is Kalman
      filtering (KF). Due to the inherent errors of low-cost MEMS inertial sensors and
      their large stochastic drifts, KF, with its linearized models, has limited
      capabilities in providing accurate positioning. Particle filtering (PF) was
      recently suggested as a nonlinear filtering technique to accommodate for
      arbitrary inertial sensor characteristics, motion dynamics and noise
      distributions. An enhanced version of PF called the Mixture PF is utilized in
      this study to perform tightly coupled integration of a three dimensional (3D)
      reduced inertial sensors system (RISS) with GPS. In this work, the RISS consists
      of one single-axis gyroscope and a two-axis accelerometer used together with the
      vehicle's odometer to obtain 3D navigation states. These sensors are then
      integrated with GPS in a tightly coupled scheme. In loosely-coupled integration,
      at least four satellites are needed to provide acceptable GPS position and
      velocity updates for the integration filter. The advantage of the tightly-coupled
      integration is that it can provide GPS measurement update(s) even when the number
      of visible satellites is three or lower, thereby improving the operation of the
      navigation system in environments with partial blockages by providing continuous
      aiding to the inertial sensors even during limited GPS satellite availability. To
      effectively exploit the capabilities of PF, advanced modeling for the stochastic
      drift of the vertically aligned gyroscope is used. In order to benefit from
      measurement updates for such drift, which are loosely-coupled updates, a hybrid
      loosely/tightly coupled solution is proposed. This solution is suitable for
      downtown environments because of the long natural outages or degradation of GPS.
      The performance of the proposed 3D Navigation solution using Mixture PF for 3D
      RISS/GPS integration is examined by road test trajectories in a land vehicle and
      compared to the KF counterpart.

PMID- 22163848
TI  - Methodology for the regulation of boom sprayers operating in circular
      trajectories.
AB  - A methodology for the regulation of boom sprayers working in circular
      trajectories has been developed. In this type of trajectory, the areas of the
      plots of land treated by the outer nozzles of the boom are treated at reduced
      rates, and those treated by the inner nozzles are treated in excess. The goal of
      this study was to establish the methodology to determine the flow of the
      individual nozzles on the boom to guarantee that the dose of the product applied
      per surface unit is similar across the plot. This flow is a function of the
      position of the equipment (circular trajectory radius) and of the displacement
      velocity such that the treatment applied per surface unit is uniform. GPS
      technology was proposed as a basis to establish the position and displacement
      velocity of the tractor. The viability of this methodology was simulated
      considering two circular plots with radii of 160 m and 310 m, using three sets of
      equipment with boom widths of 14.5, 24.5 and 29.5 m. Data showed as increasing
      boom widths produce bigger errors in the surface dose applied (L/m(2)). Error
      also increases with decreasing plot surface. As an example, considering the three
      boom widths of 14.5, 24.5 and 29.5 m working on a circular plot with a radius of
      160 m, the percentage of surface with errors in the applied surface dose greater
      than 5% was 30%, 58% and 65% respectively. Considering a circular plot with
      radius of 310 m the same errors were 8%, 22% and 31%. To obtain a uniform
      superficial dose two sprayer regulation alternatives have been simulated
      considering a 14.5 m boom: the regulation of the pressure of each nozzle and the
      regulation of the pressure of each boom section. The viability of implementing
      the proposed methodology on commercial boom sprayers using GPS antennas to
      establish the position and displacement velocity of the tractor was justified
      with a field trial in which a self-guiding commercial GPS system was used along
      with three precision GPS systems located in the sprayer boom. The use of an
      unique central GPS unit should allow the estimation of the work parameters of the
      boom nozzles (including those located at the boom ends) with great accuracy.

PMID- 22163849
TI  - Non-contact plant growth measurement method and system based on ubiquitous sensor
      network technologies.
AB  - This paper proposes a non-contact plant growth measurement system using infrared
      sensors based on the ubiquitous sensor network (USN) technology. The proposed
      system measures plant growth parameters such as the stem radius of plants using
      real-time non-contact methods, and generates diameter, cross-sectional area and
      thickening form of plant stems using this measured data. Non-contact sensors have
      been used not to cause any damage to plants during measurement of the growth
      parameters. Once the growth parameters are measured, they are transmitted to a
      remote server using the sensor network technology and analyzed in the application
      program server. The analyzed data are then provided for administrators and a
      group of interested users. The proposed plant growth measurement system has been
      designed and implemented using fixed-type and rotary-type infrared sensor based
      measurement methods and devices. Finally, the system performance is compared and
      verified with the measurement data that have been obtained by practical field
      experiments.

PMID- 22163847
TI  - Biological sensors for solar ultraviolet radiation.
AB  - Solar ultraviolet (UV) radiation is widely known as a genotoxic environmental
      agent that affects Earth ecosystems and the human population. As a primary
      consequence of the stratospheric ozone layer depletion observed over the last
      decades, the increasing UV incidence levels have heightened the concern regarding
      deleterious consequences affecting both the biosphere and humans, thereby leading
      to an increase in scientific efforts to understand the role of sunlight in the
      induction of DNA damage, mutagenesis, and cell death. In fact, the various UV
      wavelengths evoke characteristic biological impacts that greatly depend on light
      absorption of biomolecules, especially DNA, in living organisms, thereby
      justifying the increasing importance of developing biological sensors for
      monitoring the harmful impact of solar UV radiation under various environmental
      conditions. In this review, several types of biosensors proposed for laboratory
      and field application, that measure the biological effects of the UV component of
      sunlight, are described. Basically, the applicability of sensors based on DNA,
      bacteria or even mammalian cells are presented and compared. Data are also
      presented showing that on using DNA-based sensors, the various types of damage
      produced differ when this molecule is exposed in either an aqueous buffer or a
      dry solution. Apart from the data thus generated, the development of novel
      biosensors could help in evaluating the biological effects of sunlight on the
      environment. They also emerge as alternative tools for using live animals in the
      search for protective sunscreen products.

PMID- 22163850
TI  - Fused smart sensor network for multi-axis forward kinematics estimation in
      industrial robots.
AB  - Flexible manipulator robots have a wide industrial application. Robot performance
      requires sensing its position and orientation adequately, known as forward
      kinematics. Commercially available, motion controllers use high-resolution
      optical encoders to sense the position of each joint which cannot detect some
      mechanical deformations that decrease the accuracy of the robot position and
      orientation. To overcome those problems, several sensor fusion methods have been
      proposed but at expenses of high-computational load, which avoids the online
      measurement of the joint's angular position and the online forward kinematics
      estimation. The contribution of this work is to propose a fused smart sensor
      network to estimate the forward kinematics of an industrial robot. The developed
      smart processor uses Kalman filters to filter and to fuse the information of the
      sensor network. Two primary sensors are used: an optical encoder, and a 3-axis
      accelerometer. In order to obtain the position and orientation of each joint
      online a field-programmable gate array (FPGA) is used in the hardware
      implementation taking advantage of the parallel computation capabilities and
      reconfigurability of this device. With the aim of evaluating the smart sensor
      network performance, three real-operation-oriented paths are executed and
      monitored in a 6-degree of freedom robot.

PMID- 22163851
TI  - Estimation of distributed Fermat-point location for wireless sensor networking.
AB  - This work presents a localization scheme for use in wireless sensor networks
      (WSNs) that is based on a proposed connectivity-based RF localization strategy
      called the distributed Fermat-point location estimation algorithm (DFPLE). DFPLE
      applies triangle area of location estimation formed by intersections of three
      neighboring beacon nodes. The Fermat point is determined as the shortest path
      from three vertices of the triangle. The area of estimated location then refined
      using Fermat point to achieve minimum error in estimating sensor nodes location.
      DFPLE solves problems of large errors and poor performance encountered by
      localization schemes that are based on a bounding box algorithm. Performance
      analysis of a 200-node development environment reveals that, when the number of
      sensor nodes is below 150, the mean error decreases rapidly as the node density
      increases, and when the number of sensor nodes exceeds 170, the mean error
      remains below 1% as the node density increases. Second, when the number of beacon
      nodes is less than 60, normal nodes lack sufficient beacon nodes to enable their
      locations to be estimated. However, the mean error changes slightly as the number
      of beacon nodes increases above 60. Simulation results revealed that the proposed
      algorithm for estimating sensor positions is more accurate than existing
      algorithms, and improves upon conventional bounding box strategies.

PMID- 22163852
TI  - Boosting-based on-road obstacle sensing using discriminative weak classifiers.
AB  - This paper proposes an extension of the weak classifiers derived from the Haar
      like features for their use in the Viola-Jones object detection system. These
      weak classifiers differ from the traditional single threshold ones, in that no
      specific threshold is needed and these classifiers give a more general solution
      to the non-trivial task of finding thresholds for the Haar-like features. The
      proposed quadratic discriminant analysis based extension prominently improves the
      ability of the weak classifiers to discriminate objects and non-objects. The
      proposed weak classifiers were evaluated by boosting a single stage classifier to
      detect rear of car. The experiments demonstrate that the object detector based on
      the proposed weak classifiers yields higher classification performance with less
      number of weak classifiers than the detector built with traditional single
      threshold weak classifiers.

PMID- 22163853
TI  - A new HLA-based distributed control architecture for agricultural teams of robots
      in hybrid applications with real and simulated devices or environments.
AB  - The control architecture is one of the most important part of agricultural
      robotics and other robotic systems. Furthermore its importance increases when the
      system involves a group of heterogeneous robots that should cooperate to achieve
      a global goal. A new control architecture is introduced in this paper for groups
      of robots in charge of doing maintenance tasks in agricultural environments. Some
      important features such as scalability, code reuse, hardware abstraction and data
      distribution have been considered in the design of the new architecture.
      Furthermore, coordination and cooperation among the different elements in the
      system is allowed in the proposed control system. By integrating a network
      oriented device server Player, Java Agent Development Framework (JADE) and High
      Level Architecture (HLA), the previous concepts have been considered in the new
      architecture presented in this paper. HLA can be considered the most important
      part because it not only allows the data distribution and implicit communication
      among the parts of the system but also allows to simultaneously operate with
      simulated and real entities, thus allowing the use of hybrid systems in the
      development of applications.

PMID- 22163854
TI  - A secure cluster-based multipath routing protocol for WMSNs.
AB  - The new characteristics of Wireless Multimedia Sensor Network (WMSN) and its
      design issues brought by handling different traffic classes of multimedia content
      (video streams, audio, and still images) as well as scalar data over the network,
      make the proposed routing protocols for typical WSNs not directly applicable for
      WMSNs. Handling real-time multimedia data requires both energy efficiency and QoS
      assurance in order to ensure efficient utility of different capabilities of
      sensor resources and correct delivery of collected information. In this paper, we
      propose a Secure Cluster-based Multipath Routing protocol for WMSNs, SCMR, to
      satisfy the requirements of delivering different data types and support high data
      rate multimedia traffic. SCMR exploits the hierarchical structure of powerful
      cluster heads and the optimized multiple paths to support timeliness and reliable
      high data rate multimedia communication with minimum energy dissipation. Also, we
      present a light-weight distributed security mechanism of key management in order
      to secure the communication between sensor nodes and protect the network against
      different types of attacks. Performance evaluation from simulation results
      demonstrates a significant performance improvement comparing with existing
      protocols (which do not even provide any kind of security feature) in terms of
      average end-to-end delay, network throughput, packet delivery ratio, and energy
      consumption.

PMID- 22163855
TI  - Oxidation of hydrocarbons on the surface of tin dioxide chemical sensors.
AB  - The paper presents the results of our investigation on the effect of the
      molecular structure of organic vapors on the characteristics of resistive
      chemical gas sensors. The sensors were based on tin dioxide and prepared by means
      of thick film technology. The electrical and catalytic examinations showed that
      the abstraction of two hydrogen atoms from the organic molecule and formation of
      a water in result of reaction with a chemisorbed oxygen ion, determine the rate
      of oxidation reactions, and thus the sensor performance. The rate of the process
      depends on the order of carbon atoms and Lewis acidity of the molecule.
      Therefore, any modification of the surface centers of a sensor material, modifies
      not only the sensor sensitivity, but also its selectivity.

PMID- 22163856
TI  - Distributed Dynamic Host Configuration Protocol (D2HCP).
AB  - Mobile Ad Hoc Networks (MANETs) are multihop wireless networks of mobile nodes
      without any fixed or preexisting infrastructure. The topology of these networks
      can change randomly due to the unpredictable mobility of nodes and their
      propagation characteristics. In most networks, including MANETs, each node needs
      a unique identifier to communicate. This work presents a distributed protocol for
      dynamic node IP address assignment in MANETs. Nodes of a MANET synchronize from
      time to time to maintain a record of IP address assignments in the entire network
      and detect any IP address leaks. The proposed stateful autoconfiguration scheme
      uses the OLSR proactive routing protocol for synchronization and guarantees
      unique IP addresses under a variety of network conditions, including message
      losses and network partitioning. Simulation results show that the protocol incurs
      low latency and communication overhead for IP address assignment.

PMID- 22163857
TI  - Immunity-based diagnosis for a motherboard.
AB  - We have utilized immunity-based diagnosis to detect abnormal behavior of
      components on a motherboard. The immunity-based diagnostic model monitors
      voltages of some components, CPU temperatures, and fan speeds. We simulated
      abnormal behaviors of some components on the motherboard, and we utilized the
      immunity-based diagnostic model to evaluate motherboard sensors in two
      experiments. These experiments showed that the immunity-based diagnostic model
      was an effective method for detecting abnormal behavior of components on the
      motherboard.

PMID- 22163858
TI  - Next generation AT-cut quartz crystal sensing devices.
AB  - Generally, AT-cut quartz crystals have a limited scope of use when it comes to
      high-precision measurement of very small impedance changes due to their nonlinear
      frequency-temperature characteristics in the range between 0  degrees C and 50 
      degrees C. The new method improving quartz oscillator frequency-temperature
      characteristic compensation is switching between two impedance loads. By
      modifying the oscillator circuit with two logic switches and two impedance loads,
      the oscillator can switch oscillation between two resonance frequencies. The
      difference in resonance frequencies compensates the frequency-temperature
      characteristics influence as well as the influence of offset and quartz crystal
      ageing. The experimental results show that the new approach using the switching
      method highly improves second-to-second frequency stability from +/-0.125 Hz to
      +/-0.00001 Hz and minute-to-minute frequency stability from 0.1 Hz to 0.0001 Hz,
      which makes the high-precision measurement of aF and fH changes possible.

PMID- 22163859
TI  - Dynamic experiment design regularization approach to adaptive imaging with array
      radar/SAR sensor systems.
AB  - We consider a problem of high-resolution array radar/SAR imaging formalized in
      terms of a nonlinear ill-posed inverse problem of nonparametric estimation of the
      power spatial spectrum pattern (SSP) of the random wavefield scattered from a
      remotely sensed scene observed through a kernel signal formation operator and
      contaminated with random Gaussian noise. First, the Sobolev-type solution space
      is constructed to specify the class of consistent kernel SSP estimators with the
      reproducing kernel structures adapted to the metrics in such the solution space.
      Next, the "model-free" variational analysis (VA)-based image enhancement approach
      and the "model-based" descriptive experiment design (DEED) regularization
      paradigm are unified into a new dynamic experiment design (DYED) regularization
      framework. Application of the proposed DYED framework to the adaptive array
      radar/SAR imaging problem leads to a class of two-level (DEED-VA) regularized SSP
      reconstruction techniques that aggregate the kernel adaptive anisotropic
      windowing with the projections onto convex sets to enforce the consistency and
      robustness of the overall iterative SSP estimators. We also show how the proposed
      DYED regularization method may be considered as a generalization of the MVDR,
      APES and other high-resolution nonparametric adaptive radar sensing techniques. A
      family of the DYED-related algorithms is constructed and their effectiveness is
      finally illustrated via numerical simulations.

PMID- 22163860
TI  - Design and fabrication of vertically-integrated CMOS image sensors.
AB  - Technologies to fabricate integrated circuits (IC) with 3D structures are an
      emerging trend in IC design. They are based on vertical stacking of active
      components to form heterogeneous microsystems. Electronic image sensors will
      benefit from these technologies because they allow increased pixel-level data
      processing and device optimization. This paper covers general principles in the
      design of vertically-integrated (VI) CMOS image sensors that are fabricated by
      flip-chip bonding. These sensors are composed of a CMOS die and a photodetector
      die. As a specific example, the paper presents a VI-CMOS image sensor that was
      designed at the University of Alberta, and fabricated with the help of CMC
      Microsystems and Micralyne Inc. To realize prototypes, CMOS dies with logarithmic
      active pixels were prepared in a commercial process, and photodetector dies with
      metal-semiconductor-metal devices were prepared in a custom process using
      hydrogenated amorphous silicon. The paper also describes a digital camera that
      was developed to test the prototype. In this camera, scenes captured by the image
      sensor are read using an FPGA board, and sent in real time to a PC over USB for
      data processing and display. Experimental results show that the VI-CMOS prototype
      has a higher dynamic range and a lower dark limit than conventional electronic
      image sensors.

PMID- 22163861
TI  - Study on the context-aware middleware for ubiquitous greenhouses using wireless
      sensor networks.
AB  - Wireless Sensor Network (WSN) technology is one of the important technologies to
      implement the ubiquitous society, and it could increase productivity of
      agricultural and livestock products, and secure transparency of distribution
      channels if such a WSN technology were successfully applied to the agricultural
      sector. Middleware, which can connect WSN hardware, applications, and enterprise
      systems, is required to construct ubiquitous agriculture environment combining
      WSN technology with agricultural sector applications, but there have been
      insufficient studies in the field of WSN middleware in the agricultural
      environment, compared to other industries. This paper proposes a context-aware
      middleware to efficiently process data collected from ubiquitous greenhouses by
      applying WSN technology and used to implement combined services through organic
      connectivity of data. The proposed middleware abstracts heterogeneous sensor
      nodes to integrate different forms of data, and provides intelligent context
      aware, event service, and filtering functions to maximize operability and
      scalability of the middleware. To evaluate the performance of the middleware, an
      integrated management system for ubiquitous greenhouses was implemented by
      applying the proposed middleware to an existing greenhouse, and it was tested by
      measuring the level of load through CPU usage and the response time for users'
      requests when the system is working.

PMID- 22163862
TI  - Optimization of urea-EnFET based on Ta2O5 layer with post annealing.
AB  - In this study, the urea-enzymatic field effect transistors (EnFETs) were
      investigated based on pH-ion sensitive field effect transistors (ISFETs) with
      tantalum pentoxide (Ta(2)O(5)) sensing membranes. In addition, a post N(2)
      annealing was used to improve the sensing properties. At first, the pH
      sensitivity, hysteresis, drift, and light induced drift of the ISFETs were
      evaluated. After the covalent bonding process and urease immobilization, the urea
      sensitivity of the EnFETs were also investigated and compared with the
      conventional Si(3)N(4) sensing layer. The ISFETs and EnFETs with annealed
      Ta(2)O(5) sensing membranes showed the best responses, including the highest pH
      sensitivity (56.9 mV/pH, from pH 2 to pH 12) and also corresponded to the highest
      urea sensitivity (61 mV/pC(urea), from 1 mM to 7.5 mM). Besides, the non-ideal
      factors of pH hysteresis, time drift, and light induced drift of the annealed
      samples were also lower than the controlled Ta(2)O(5) and Si(3)N(4) sensing
      membranes.

PMID- 22163864
TI  - Fluorescent sensing of chlorophenols in water using an azo dye modified beta
      cyclodextrin polymer.
AB  - A water soluble azo dye modified beta-cyclodextrin polymer 4 was synthesized and
      used as a chemosensor for the detection of chlorinated phenols, model chlorinated
      by-products (CBPs) of water treatment for drinking purposes. The characterization
      of the intermediates and the azo dye modified beta-CD polymer was done by UV/Vis
      Spectrophotometry, FT-IR and (1)H-NMR spectroscopies. The chlorophenols were
      capable of quenching the fluorescence of the polymer. The polymer showed greater
      sensitivity towards 2,4-dichlorophenol, with a sensitivity factor of 0.35
      compared to 0.05 and 0.12 for phenol and 4-chlorophenol, respectively. The
      stability constants (K(s)) of the pollutants were also determined by the Benesi
      Hildebrand method to be 2.104 * 10(3) M(-1) for 2,4-dichlorophenol and 1.120 *
      10(2) M(-1) for 4-chlorophenol.

PMID- 22163863
TI  - Recent advances in neural recording microsystems.
AB  - The accelerating pace of research in neuroscience has created a considerable
      demand for neural interfacing microsystems capable of monitoring the activity of
      large groups of neurons. These emerging tools have revealed a tremendous
      potential for the advancement of knowledge in brain research and for the
      development of useful clinical applications. They can extract the relevant
      control signals directly from the brain enabling individuals with severe
      disabilities to communicate their intentions to other devices, like computers or
      various prostheses. Such microsystems are self-contained devices composed of a
      neural probe attached with an integrated circuit for extracting neural signals
      from multiple channels, and transferring the data outside the body. The greatest
      challenge facing development of such emerging devices into viable clinical
      systems involves addressing their small form factor and low-power consumption
      constraints, while providing superior resolution. In this paper, we survey the
      recent progress in the design and the implementation of multi-channel neural
      recording Microsystems, with particular emphasis on the design of recording and
      telemetry electronics. An overview of the numerous neural signal modalities is
      given and the existing microsystem topologies are covered. We present energy
      efficient sensory circuits to retrieve weak signals from neural probes and we
      compare them. We cover data management and smart power scheduling approaches, and
      we review advances in low-power telemetry. Finally, we conclude by summarizing
      the remaining challenges and by highlighting the emerging trends in the field.

PMID- 22163865
TI  - An electronic-nose sensor node based on a polymer-coated surface acoustic wave
      array for wireless sensor network applications.
AB  - This study developed an electronic-nose sensor node based on a polymer-coated
      surface acoustic wave (SAW) sensor array. The sensor node comprised an SAW sensor
      array, a frequency readout circuit, and an Octopus II wireless module. The sensor
      array was fabricated on a large K(2) 128 degrees  YX LiNbO3 sensing substrate. On
      the surface of this substrate, an interdigital transducer (IDT) was produced with
      a Cr/Au film as its metallic structure. A mixed-mode frequency readout
      application specific integrated circuit (ASIC) was fabricated using a TSMC 0.18
      MUm process. The ASIC output was connected to a wireless module to transmit
      sensor data to a base station for data storage and analysis. This sensor node is
      applicable for wireless sensor network (WSN) applications.

PMID- 22163866
TI  - A new data mining scheme using artificial neural networks.
AB  - Classification is one of the data mining problems receiving enormous attention in
      the database community. Although artificial neural networks (ANNs) have been
      successfully applied in a wide range of machine learning applications, they are
      however often regarded as black boxes, i.e., their predictions cannot be
      explained. To enhance the explanation of ANNs, a novel algorithm to extract
      symbolic rules from ANNs has been proposed in this paper. ANN methods have not
      been effectively utilized for data mining tasks because how the classifications
      were made is not explicitly stated as symbolic rules that are suitable for
      verification or interpretation by human experts. With the proposed approach,
      concise symbolic rules with high accuracy, that are easily explainable, can be
      extracted from the trained ANNs. Extracted rules are comparable with other
      methods in terms of number of rules, average number of conditions for a rule, and
      the accuracy. The effectiveness of the proposed approach is clearly demonstrated
      by the experimental results on a set of benchmark data mining classification
      problems.

PMID- 22163867
TI  - Investigation of a photoelectrochemical passivated ZnO-based glucose biosensor.
AB  - A vapor cooling condensation system was used to deposit high quality intrinsic
      ZnO thin films and intrinsic ZnO nanorods as the sensing membrane of extended
      gate field-effect-transistor (EGFET) glucose biosensors. The sensing sensitivity
      of the resulting glucose biosensors operated in the linear range was 13.4 MUA mM(
      1) cm(-2). To improve the sensing sensitivity of the ZnO-based glucose
      biosensors, the photoelectrochemical method was utilized to passivate the
      sidewall surfaces of the ZnO nanorods. The sensing sensitivity of the ZnO-based
      glucose biosensors with passivated ZnO nanorods was significantly improved to
      20.33 MUA mM(-1) cm(-2) under the same measurement conditions. The experimental
      results verified that the sensing sensitivity improvement was the result of the
      mitigation of the Fermi level pinning effect caused by the dangling bonds and the
      surface states induced on the sidewall surface of the ZnO nanorods.

PMID- 22163868
TI  - Soft water level sensors for characterizing the hydrological behaviour of
      agricultural catchments.
AB  - An innovative soft water level sensor is proposed to characterize the
      hydrological behaviour of agricultural catchments by measuring rainfall and
      stream flows. This sensor works as a capacitor coupled with a capacitance to
      frequency converter and measures water level at an adjustable time step
      acquisition. It was designed to be handy, minimally invasive and optimized in
      terms of energy consumption and low-cost fabrication so as to multiply its use on
      several catchments under natural conditions. It was used as a stage recorder to
      measure water level dynamics in a channel during a runoff event and as a rain
      gauge to measure rainfall amount and intensity. Based on the Manning equation, a
      method allowed estimation of water discharge with a given uncertainty and hence
      runoff volume at an event or annual scale. The sensor was tested under controlled
      conditions in the laboratory and under real conditions in the field. Comparisons
      of the sensor to reference devices (tipping bucket rain gauge, hydrostatic
      pressure transmitter limnimeter, Venturi channels...) showed accurate results:
      rainfall intensities and dynamic responses were accurately reproduced and
      discharges were estimated with an uncertainty usually acceptable in hydrology.
      Hence, it was used to monitor eleven small agricultural catchments located in the
      Mediterranean region. Both catchment reactivity and water budget have been
      calculated. Dynamic response of the catchments has been studied at the event
      scale through the rising time determination and at the annual scale by
      calculating the frequency of occurrence of runoff events. It provided significant
      insight into catchment hydrological behaviour which could be useful for
      agricultural management perspectives involving pollutant transport, flooding
      event and global water balance.

PMID- 22163869
TI  - A novel ionic polymer metal ZnO composite (IPMZC).
AB  - The presented research introduces a new Ionic Polymer-Metal-ZnO Composite (IPMZC)
      demonstrating photoluminescence (PL)-quenching on mechanical bending or
      application of an electric field. The newly fabricated IPMZC integrates the
      optical properties of ZnO and the electroactive nature of Ionic Polymer Metal
      Composites (IPMC) to enable a non-contact read-out of IPMC response. The electro
      mechano-optical response of the IPMZC was measured by observing the PL spectra
      under mechanical bending and electrical regimes. The working range was measured
      to be 375-475 nm. It was noted that the PL-quenching increased proportionally
      with the increase in curvature and applied field at 384 and 468 nm. The maximum
      quenching of 53.4% was achieved with the membrane curvature of 78.74/m and 3.01%
      when electric field (12.5 * 10(3) V/m) is applied. Coating IPMC with crystalline
      ZnO was observed to improve IPMC transduction.

PMID- 22163870
TI  - Potentiometric electronic tongues for foodstuff and biosample recognition--an
      overview.
AB  - Potentiometric sensors are attractive tools for the fabrication of various
      electronic tongues that can be used in wide area of applications, ranging from
      foodstuff recognition to environmental monitoring and medical diagnostics. Their
      main advantages are the ability to modify their selectivity (including cross
      sensitivity effects) and the possibility of miniaturization using appropriate
      construction methods for the transducer part (e.g., with the use of solid-state
      technology). In this overview various examples of the design, performance, and
      applications of potentiometric electronic tongues are presented. The results
      summarize recent research in the field conducted in the Department of
      Microbioanalytics, Warsaw University of Technology (WUT).

PMID- 22163871
TI  - Validation of a phase-mass characterization concept and interface for acoustic
      biosensors.
AB  - Acoustic wave resonator techniques are widely used in in-liquid biochemical
      applications. The main challenges remaining are the improvement of sensitivity
      and limit of detection, as well as multianalysis capabilities and reliability.
      The sensitivity improvement issue has been addressed by increasing the sensor
      frequency, using different techniques such as high fundamental frequency quartz
      crystal microbalances (QCMs), surface generated acoustic waves (SGAWs) and film
      bulk acoustic resonators (FBARs). However, this sensitivity improvement has not
      been completely matched in terms of limit of detection. The decrease on frequency
      stability due to the increase of the phase noise, particularly in oscillators,
      has made it impossible to increase the resolution. A new concept of sensor
      characterization at constant frequency has been recently proposed based on the
      phase/mass sensitivity equation: Deltaphi/Deltam ~ -1/m(L), where m(L) is the
      liquid mass perturbed by the resonator. The validation of the new concept is
      presented in this article. An immunosensor application for the detection of a low
      molecular weight pollutant, the insecticide carbaryl, has been chosen as a
      validation model.

PMID- 22163872
TI  - Crop classification by forward neural network with adaptive chaotic particle
      swarm optimization.
AB  - This paper proposes a hybrid crop classifier for polarimetric synthetic aperture
      radar (SAR) images. The feature sets consisted of span image, the H/A/alpha
      decomposition, and the gray-level co-occurrence matrix (GLCM) based texture
      features. Then, the features were reduced by principle component analysis (PCA).
      Finally, a two-hidden-layer forward neural network (NN) was constructed and
      trained by adaptive chaotic particle swarm optimization (ACPSO). K-fold cross
      validation was employed to enhance generation. The experimental results on
      Flevoland sites demonstrate the superiority of ACPSO to back-propagation (BP),
      adaptive BP (ABP), momentum BP (MBP), Particle Swarm Optimization (PSO), and
      Resilient back-propagation (RPROP) methods. Moreover, the computation time for
      each pixel is only 1.08 * 10(-7) s.

PMID- 22163873
TI  - Electronic noses and tongues: applications for the food and pharmaceutical
      industries.
AB  - The electronic nose (e-nose) is designed to crudely mimic the mammalian nose in
      that most contain sensors that non-selectively interact with odor molecules to
      produce some sort of signal that is then sent to a computer that uses
      multivariate statistics to determine patterns in the data. This pattern
      recognition is used to determine that one sample is similar or different from
      another based on headspace volatiles. There are different types of e-nose sensors
      including organic polymers, metal oxides, quartz crystal microbalance and even
      gas-chromatography (GC) or combined with mass spectroscopy (MS) can be used in a
      non-selective manner using chemical mass or patterns from a short GC column as an
      e-nose or "Z" nose. The electronic tongue reacts similarly to non-volatile
      compounds in a liquid. This review will concentrate on applications of e-nose and
      e-tongue technology for edible products and pharmaceutical uses.

PMID- 22163874
TI  - A secured authentication protocol for wireless sensor networks using elliptic
      curves cryptography.
AB  - User authentication is a crucial service in wireless sensor networks (WSNs) that
      is becoming increasingly common in WSNs because wireless sensor nodes are
      typically deployed in an unattended environment, leaving them open to possible
      hostile network attack. Because wireless sensor nodes are limited in computing
      power, data storage and communication capabilities, any user authentication
      protocol must be designed to operate efficiently in a resource constrained
      environment. In this paper, we review several proposed WSN user authentication
      protocols, with a detailed review of the M.L Das protocol and a cryptanalysis of
      Das' protocol that shows several security weaknesses. Furthermore, this paper
      proposes an ECC-based user authentication protocol that resolves these
      weaknesses. According to our analysis of security of the ECC-based protocol, it
      is suitable for applications with higher security requirements. Finally, we
      present a comparison of security, computation, and communication costs and
      performances for the proposed protocols. The ECC-based protocol is shown to be
      suitable for higher security WSNs.

PMID- 22163875
TI  - Adaptive sparse representation for source localization with gain/phase errors.
AB  - Sparse representation (SR) algorithms can be implemented for high-resolution
      direction of arrival (DOA) estimation. Additionally, SR can effectively separate
      the coherent signal sources because the spectrum estimation is based on the
      optimization technique, such as the L(1) norm minimization, but not on subspace
      orthogonality. However, in the actual source localization scenario, an unknown
      gain/phase error between the array sensors is inevitable. Due to this nonideal
      factor, the predefined overcomplete basis mismatches the actual array manifold so
      that the estimation performance is degraded in SR. In this paper, an adaptive SR
      algorithm is proposed to improve the robustness with respect to the gain/phase
      error, where the overcomplete basis is dynamically adjusted using multiple
      snapshots and the sparse solution is adaptively acquired to match with the actual
      scenario. The simulation results demonstrate the estimation robustness to the
      gain/phase error using the proposed method.

PMID- 22163876
TI  - Information potential fields navigation in wireless ad-hoc sensor networks.
AB  - As wireless sensor networks (WSNs) are increasingly being deployed in some
      important applications, it becomes imperative that we consider application
      requirements in in-network processes. We intend to use a WSN to aid information
      querying and navigation within a dynamic and real-time environment. We propose a
      novel method that relies on the heat diffusion equation to finish the navigation
      process conveniently and easily. From the perspective of theoretical analysis,
      our proposed work holds the lower constraint condition. We use multiple scales to
      reach the goal of accurate navigation. We present a multi-scale gradient descent
      method to satisfy users' requirements in WSNs. Formula derivations and
      simulations show that the method is accurately and efficiently able to solve
      typical sensor network configuration information navigation problems.
      Simultaneously, the structure of heat diffusion equation allows more flexibility
      and adaptability in searching algorithm designs.

PMID- 22163877
TI  - Enhancement of optical adaptive sensing by using a dual-stage seesaw-swivel
      actuator with a tunable vibration absorber.
AB  - Technological obstacles to the use of rotary-type swing arm actuators to actuate
      optical pickup modules in small-form-factor (SFF) disk drives stem from a hinge's
      skewed actuation, subsequently inducing off-axis aberrations and deteriorating
      optical quality. This work describes a dual-stage seesaw-swivel actuator for
      optical pickup actuation. A triple-layered bimorph bender made of piezoelectric
      materials (PZTs) is connected to the suspension of the pickup head, while the
      tunable vibration absorber (TVA) unit is mounted on the seesaw swing arm to offer
      a balanced force to reduce vibrations in a focusing direction. Both PZT and TVA
      are designed to satisfy stable focusing operation operational requirements and
      compensate for the tilt angle or deformation of a disc. Finally, simulation
      results verify the performance of the dual-stage seesaw-swivel actuator, along
      with experimental procedures and parametric design optimization confirming the
      effectiveness of the proposed system.

PMID- 22163878
TI  - Rapid assessment of mineral concentration in meadow grasses by near infrared
      reflectance spectroscopy.
AB  - A near infrared reflectance spectroscopy (NIRS) method for rapid determination of
      nitrogen, phosphorous and potassium in diverse meadow grasses was developed with
      a view towards utilizing this material for biogas production and organic
      fertilizer. NIRS spectra between 12,000 cm(-1) and 4,000 cm(-1) were used. When
      validated on samples from different years to those used for the calibration set,
      the NIRS prediction of nitrogen was considered moderately useful with R(2) =
      0.77, ratio of standard error of prediction to reference data range (RER) of 9.32
      and ratio of standard error of prediction to standard deviation of reference data
      (RPD) of 2.33. Prediction of potassium was less accurate, with R(2) = 0.77, RER
      of 6.56 and RPD of 1.45, whilst prediction of phosphorous was not considered
      accurate enough to be of any practical use. This work is of interest from the
      point of view of both the removal of excess nutrients from formerly intensively
      farmed areas and also for assessing the plant biomass suitability for conversion
      into carbon neutral energy through biogas production.

PMID- 22163879
TI  - Application of an e-tongue to the analysis of monovarietal and blends of white
      wines.
AB  - This work presents a multiparametric system capable of characterizing and
      classifying white wines according to the grape variety and geographical origin.
      Besides, it quantifies specific parameters of interest for quality control in
      wine. The system, known as a hybrid electronic tongue, consists of an array of
      electrochemical microsensors-six ISFET based sensors, a conductivity sensor, a
      redox potential sensor and two amperometric electrodes, a gold microelectrode and
      a microelectrode for sensing electrochemical oxygen demand--and a miniaturized
      optofluidic system. The test sample set comprised eighteen Catalan monovarietal
      white wines from four different grape varieties, two Croatian monovarietal white
      wines and seven bi- and trivarietal mixtures prepared from the Catalan varieties.
      Different chemometric tools were used to characterize (i.e., Principal Component
      Analysis), classify (i.e., Soft Independent Modeling Class Analogy) and quantify
      (i.e., Partial-Least Squares) some parameters of interest. The results
      demonstrate the usefulness of the multisensor system for analysis of wine.

PMID- 22163880
TI  - Improved calibration functions of three capacitance probes for the measurement of
      soil moisture in tropical soils.
AB  - Single capacitance sensors are sensitive to soil property variability. The
      objectives of this study were to: (i) establish site-specific laboratory
      calibration equations of three single capacitance sensors (EC-20, EC-10, and
      ML2x) for tropical soils, and (ii) evaluate the accuracy and precision of these
      sensors. Intact soil cores and bulk samples, collected from the top 20 and 80 cm
      soil depths at five locations across the Upper Makaha Valley watershed, were
      analyzed to determine their soil bulk density (rho(b)), total porosity
      (theta(t)), particle size distribution, and electrical conductivity (EC).
      Laboratory calibration equations were established using soil packed columns at
      six water content levels (0-0.5 cm(3) cm(-3)). Soil bulk density and theta(t)
      significantly varied with sampling depths; whereas, soil clay content (CC) and EC
      varied with sampling locations. Variations of rho(b) and theta(t) at the two
      depths significantly affected the EC-20 and ML2x laboratory calibration
      functions; however, there was no effect of these properties on calibration
      equation functions of EC-10. There was no significant effect of sampling
      locations on the laboratory calibration functions suggesting watershed-specific
      equations for EC-20 and ML2x for the two depths; a single watershed-specific
      equation was needed for EC-10 for both sampling depths. The laboratory
      calibration equations for all sensors were more accurate than the corresponding
      default equations. ML2x exhibited better precision than EC-10, followed by EC-20.
      We conclude that the laboratory calibration equations can mitigate the effects of
      varying soil properties and improve the sensors' accuracy for water content
      measurements.

PMID- 22163881
TI  - A survey of system architecture requirements for health care-based wireless
      sensor networks.
AB  - Wireless Sensor Networks (WSNs) have emerged as a viable technology for a vast
      number of applications, including health care applications. To best support these
      health care applications, WSN technology can be adopted for the design of
      practical Health Care WSNs (HCWSNs) that support the key system architecture
      requirements of reliable communication, node mobility support, multicast
      technology, energy efficiency, and the timely delivery of data. Work in the
      literature mostly focuses on the physical design of the HCWSNs (e.g., wearable
      sensors, in vivo embedded sensors, et cetera). However, work towards enhancing
      the communication layers (i.e., routing, medium access control, et cetera) to
      improve HCWSN performance is largely lacking. In this paper, the information
      gleaned from an extensive literature survey is shared in an effort to fortify the
      knowledge base for the communication aspect of HCWSNs. We highlight the major
      currently existing prototype HCWSNs and also provide the details of their routing
      protocol characteristics. We also explore the current state of the art in medium
      access control (MAC) protocols for WSNs, for the purpose of seeking an energy
      efficient solution that is robust to mobility and delivers data in a timely
      fashion. Furthermore, we review a number of reliable transport layer protocols,
      including a network coding based protocol from the literature, that are
      potentially suitable for delivering end-to-end reliability of data transmitted in
      HCWSNs. We identify the advantages and disadvantages of the reviewed MAC,
      routing, and transport layer protocols as they pertain to the design and
      implementation of a HCWSN. The findings from this literature survey will serve as
      a useful foundation for designing a reliable HCWSN and also contribute to the
      development and evaluation of protocols for improving the performance of future
      HCWSNs. Open issues that required further investigations are highlighted.

PMID- 22163882
TI  - Use of the electronic nose as a screening tool for the recognition of durum wheat
      naturally contaminated by deoxynivalenol: a preliminary approach.
AB  - Fungal contamination and the presence of related toxins is a widespread problem.
      Mycotoxin contamination has prompted many countries to establish appropriate
      tolerance levels. For instance, with the Commission Regulation (EC) N. 1881/2006,
      the European Commission fixed the limits for the main mycotoxins (and other
      contaminants) in food. Although valid analytical methods are being developed for
      regulatory purposes, a need exists for alternative screening methods that can
      detect mould and mycotoxin contamination of cereal grains with high sample
      throughput. In this study, a commercial electronic nose (EN) equipped with metal
      oxide-semiconductor (MOS) sensors was used in combination with a trap and the
      thermal desorption technique, with the adoption of Tenax TA as an adsorbent
      material to discriminate between durum wheat whole-grain samples naturally
      contaminated with deoxynivalenol (DON) and non-contaminated samples. Each wheat
      sample was analysed with the EN at four different desorption temperatures (i.e.,
      180  degrees C, 200  degrees C, 220  degrees C, and 240  degrees C) and without a
      desorption pre-treatment. A 20-sample and a 122-sample dataset were processed by
      means of principal component analysis (PCA) and classified via classification and
      regression trees (CART). Results, validated with two different methods, showed
      that it was possible to classify wheat samples into three clusters based on the
      DON content proposed by the European legislation: (a) non-contaminated; (b)
      contaminated below the limit (DON < 1,750 MUg/kg); (c) contaminated above the
      limit (DON > 1,750 MUg/kg), with a classification error rate in prediction of 0%
      (for the 20-sample dataset) and 3.28% (for the 122-sample dataset).

PMID- 22163883
TI  - Multi-channel multi-radio using 802.11 based media access for sink nodes in
      wireless sensor networks.
AB  - The next generation surveillance and multimedia systems will become increasingly
      deployed as wireless sensor networks in order to monitor parks, public places and
      for business usage. The convergence of data and telecommunication over IP-based
      networks has paved the way for wireless networks. Functions are becoming more
      intertwined by the compelling force of innovation and technology. For example,
      many closed-circuit TV premises surveillance systems now rely on transmitting
      their images and data over IP networks instead of standalone video circuits.
      These systems will increase their reliability in the future on wireless networks
      and on IEEE 802.11 networks. However, due to limited non-overlapping channels,
      delay, and congestion there will be problems at sink nodes. In this paper we
      provide necessary conditions to verify the feasibility of round robin technique
      in these networks at the sink nodes by using a technique to regulate multi-radio
      multichannel assignment. We demonstrate through simulations that dynamic channel
      assignment scheme using multi-radio, and multichannel configuration at a single
      sink node can perform close to optimal on the average while multiple sink node
      assignment also performs well. The methods proposed in this paper can be a
      valuable tool for network designers in planning network deployment and for
      optimizing different performance objectives.

PMID- 22163885
TI  - Two-scale simulation of drop-induced failure of polysilicon MEMS sensors.
AB  - In this paper, an industrially-oriented two-scale approach is provided to model
      the drop-induced brittle failure of polysilicon MEMS sensors. The two length
      scales here investigated are the package (macroscopic) and the sensor
      (mesoscopic) ones. Issues related to the polysilicon morphology at the micro
      scale are disregarded; an upscaled homogenized constitutive law, able to describe
      the brittle cracking of silicon, is instead adopted at the meso-scale. The two
      scale approach is validated against full three-scale Monte-Carlo simulations,
      which allow for stochastic effects linked to the microstructural properties of
      polysilicon. Focusing on inertial MEMS sensors exposed to drops, it is shown that
      the offered approach matches well the experimentally observed failure mechanisms.

PMID- 22163884
TI  - Commercialisation of CMOS integrated circuit technology in multi-electrode arrays
      for neuroscience and cell-based biosensors.
AB  - The adaptation of standard integrated circuit (IC) technology as a transducer in
      cell-based biosensors in drug discovery pharmacology, neural interface systems
      and electrophysiology requires electrodes that are electrochemically stable,
      biocompatible and affordable. Unfortunately, the ubiquitous Complementary Metal
      Oxide Semiconductor (CMOS) IC technology does not meet the first of these
      requirements. For devices intended only for research, modification of CMOS by
      post-processing using cleanroom facilities has been achieved. However, to enable
      adoption of CMOS as a basis for commercial biosensors, the economies of scale of
      CMOS fabrication must be maintained by using only low-cost post-processing
      techniques. This review highlights the methodologies employed in cell-based
      biosensor design where CMOS-based integrated circuits (ICs) form an integral part
      of the transducer system. Particular emphasis will be placed on the application
      of multi-electrode arrays for in vitro neuroscience applications. Identifying
      suitable IC packaging methods presents further significant challenges when
      considering specific applications. The various challenges and difficulties are
      reviewed and some potential solutions are presented.

PMID- 22163886
TI  - A diagnostic system for improving biomass quality based on a sensor network.
AB  - Losses during storage of biomass are the main parameter that defines the
      profitability of using preserved biomass as feed for animal husbandry. In order
      to minimize storage losses, potential changes in specific physicochemical
      properties must be identified to subsequently act as indicators of silage
      decomposition and form the basis for preventive measures. This study presents a
      framework for a diagnostic system capable of detecting potential changes in
      specific physicochemical properties, i.e., temperature and the oxygen content,
      during the biomass storage process. The diagnostic system comprises a monitoring
      tool based on a wireless sensors network and a prediction tool based on a
      validated computation fluid dynamics model. It is shown that the system can
      provide the manager (end-user) with continuously updated information about
      specific biomass quality parameters. The system encompasses graphical
      visualization of the information to the end-user as a first step and, as a second
      step, the system identifies alerts depicting real differences between actual and
      predicted values of the monitored properties. The perspective is that this
      diagnostic system will provide managers with a solid basis for necessary
      preventive measures.

PMID- 22163887
TI  - Electronic nose based on an optimized competition neural network.
AB  - In view of the fact that there are disadvantages in that the class number must be
      determined in advance, the value of learning rates are hard to fix, etc., when
      using traditional competitive neural networks (CNNs) in electronic noses (E
      noses), an optimized CNN method was presented. The optimized CNN was established
      on the basis of the optimum class number of samples according to the changes of
      the Davies and Bouldin (DB) value and it could increase, divide, or delete
      neurons in order to adjust the number of neurons automatically. Moreover, the
      learning rate changes according to the variety of training times of each sample.
      The traditional CNN and the optimized CNN were applied to five kinds of sorted
      vinegars with an E-nose. The results showed that optimized network structures
      could adjust the number of clusters dynamically and resulted in good
      classifications.

PMID- 22163888
TI  - RUASN: a robust user authentication framework for wireless sensor networks.
AB  - In recent years, wireless sensor networks (WSNs) have been considered as a
      potential solution for real-time monitoring applications and these WSNs have
      potential practical impact on next generation technology too. However, WSNs could
      become a threat if suitable security is not considered before the deployment and
      if there are any loopholes in their security, which might open the door for an
      attacker and hence, endanger the application. User authentication is one of the
      most important security services to protect WSN data access from unauthorized
      users; it should provide both mutual authentication and session key establishment
      services. This paper proposes a robust user authentication framework for wireless
      sensor networks, based on a two-factor (password and smart card) concept. This
      scheme facilitates many services to the users such as user anonymity, mutual
      authentication, secure session key establishment and it allows users to
      choose/update their password regularly, whenever needed. Furthermore, we have
      provided the formal verification using Rubin logic and compare RUASN with many
      existing schemes. As a result, we found that the proposed scheme possesses many
      advantages against popular attacks, and achieves better efficiency at low
      computation cost.

PMID- 22163889
TI  - Performance of a CO2 impedimetric sensor prototype for air quality monitoring.
AB  - Carbon dioxide detection is a relevant issue in many fields, and this work
      focuses on the use of a BaTiO(3)-CuO sputtered thin film layer in a gas sensor
      prototype for air quality measurements. For this, a double side sensor was
      fabricated, with a Pt heater on one side and the sensing layer over the
      electrodes on the other side. The uniformity of the temperature on the sensing
      layer was tested and further tests to check its sensing performance were carried
      out. Humidity influence in the detection was found to be almost negligible within
      the usual range in air quality measurements and repeatability tests show
      satisfactory results for air quality control purposes.

PMID- 22163891
TI  - Measuring oscillating walking paths with a LIDAR.
AB  - This work describes the analysis of different walking paths registered using a
      Light Detection And Ranging (LIDAR) laser range sensor in order to measure
      oscillating trajectories during unsupervised walking. The estimate of the gait
      and trajectory parameters were obtained with a terrestrial LIDAR placed 100 mm
      above the ground with the scanning plane parallel to the floor to measure the
      trajectory of the legs without attaching any markers or modifying the floor.
      Three different large walking experiments were performed to test the proposed
      measurement system with straight and oscillating trajectories. The main
      advantages of the proposed system are the possibility to measure several steps
      and obtain average gait parameters and the minimum infrastructure required. This
      measurement system enables the development of new ambulatory applications based
      on the analysis of the gait and the trajectory during a walk.

PMID- 22163890
TI  - Development of a stepping force analgesic meter for a rat arthritic model.
AB  - Behavioural assessment of experimental pain is an essential method for analysing
      and measuring pain levels. Rodent models, which are widely used in behavioural
      tests, are often subject to external forces and stressful manipulations that
      cause variability of the parameters measured during the experiment. Therefore,
      these parameters may be inappropriate as indicators of pain. In this article, a
      stepping-force analgesimeter was designed to investigate the variations in the
      stepping force of rats in response to pain induction. The proposed apparatus
      incorporates new features, namely an infrared charge-coupled device (CCD) camera
      and a data acquisition system. The camera was able to capture the locomotion of
      the rats and synchronise the stepping force concurrently so that each step could
      be identified. Inter-day and intra-day precision and accuracy of each channel
      (there were a total of eight channels in the analgesimeter and each channel was
      connected to one load cell and one amplifier) were studied using different
      standard load weights. The validation studies for each channel also showed
      convincing results whereby intra-day and inter-day precision were less than 1%
      and accuracy was 99.36-100.36%. Consequently, an in vivo test was carried out
      using 16 rats (eight females and eight males). The rats were allowed to randomly
      walk across the sensor tunnel (the area that contained eight channels) and the
      stepping force and locomotion were recorded. A non-expert, but from a related
      research domain, was asked to differentiate the peaks of the front and hind paw,
      respectively. The results showed that of the total movement generated by the
      rats, 50.27 +/- 3.90% in the case of the male rats and 62.20 +/- 6.12% in that of
      the female rats had more than two peaks, a finding which does not substantiate
      the assumptions made in previous studies. This study also showed that there was a
      need to use the video display frame to distinguish between the front and hind
      paws in the case of 48.80 +/- 4.01% of the male rats and 66.76 +/- 5.35% of the
      female rats. Evidently the assumption held by current researchers regarding
      stepping force measurement is not realistic in terms of application, and as this
      study has shown, the use of a video display frame is essential for the
      identification of the front and hind paws through the peak signals.

PMID- 22163892
TI  - Protein biosensors based on polymer nanowires, carbon nanotubes and zinc oxide
      nanorods.
AB  - The development of biosensors using electrochemical methods is a promising
      application in the field of biotechnology. High sensitivity sensors for the bio
      detection of proteins have been developed using several kinds of nanomaterials.
      The performance of the sensors depends on the type of nanostructures with which
      the biomaterials interact. One dimensional (1-D) structures such as nanowires,
      nanotubes and nanorods are proven to have high potential for bio-applications. In
      this paper we review these three different kinds of nanostructures that have
      attracted much attention at recent times with their great performance as
      biosensors. Materials such as polymers, carbon and zinc oxide have been widely
      used for the fabrication of nanostructures because of their enhanced performance
      in terms of sensitivity, biocompatibility, and ease of preparation. Thus we
      consider polymer nanowires, carbon nanotubes and zinc oxide nanorods for
      discussion in this paper. We consider three stages in the development of
      biosensors: (a) fabrication of biomaterials into nanostructures, (b) alignment of
      the nanostructures and (c) immobilization of proteins. Two different methods by
      which the biosensors can be developed at each stage for all the three
      nanostructures are examined. Finally, we conclude by mentioning some of the major
      challenges faced by many researchers who seek to fabricate biosensors for real
      time applications.

PMID- 22163893
TI  - Amorphous and polycrystalline photoconductors for direct conversion flat panel x
      ray image sensors.
AB  - In the last ten to fifteen years there has been much research in using amorphous
      and polycrystalline semiconductors as x-ray photoconductors in various x-ray
      image sensor applications, most notably in flat panel x-ray imagers (FPXIs). We
      first outline the essential requirements for an ideal large area photoconductor
      for use in a FPXI, and discuss how some of the current amorphous and
      polycrystalline semiconductors fulfill these requirements. At present, only
      stabilized amorphous selenium (doped and alloyed a-Se) has been commercialized,
      and FPXIs based on a-Se are particularly suitable for mammography, operating at
      the ideal limit of high detective quantum efficiency (DQE). Further, these FPXIs
      can also be used in real-time, and have already been used in such applications as
      tomosynthesis. We discuss some of the important attributes of amorphous and
      polycrystalline x-ray photoconductors such as their large area deposition
      ability, charge collection efficiency, x-ray sensitivity, DQE, modulation
      transfer function (MTF) and the importance of the dark current. We show the
      importance of charge trapping in limiting not only the sensitivity but also the
      resolution of these detectors. Limitations on the maximum acceptable dark current
      and the corresponding charge collection efficiency jointly impose a practical
      constraint that many photoconductors fail to satisfy. We discuss the case of a-Se
      in which the dark current was brought down by three orders of magnitude by the
      use of special blocking layers to satisfy the dark current constraint. There are
      also a number of polycrystalline photoconductors, HgI(2) and PbO being good
      examples, that show potential for commercialization in the same way that
      multilayer stabilized a-Se x-ray photoconductors were developed for commercial
      applications. We highlight the unique nature of avalanche multiplication in a-Se
      and how it has led to the development of the commercial HARP video-tube. An all
      solid state version of the HARP has been recently demonstrated with excellent
      avalanche gains; the latter is expected to lead to a number of novel imaging
      device applications that would be quantum noise limited. While passive pixel
      sensors use one TFT (thin film transistor) as a switch at the pixel, active pixel
      sensors (APSs) have two or more transistors and provide gain at the pixel level.
      The advantages of APS based x-ray imagers are also discussed with examples.

PMID- 22163894
TI  - Tree classification with fused mobile laser scanning and hyperspectral data.
AB  - Mobile Laser Scanning data were collected simultaneously with hyperspectral data
      using the Finnish Geodetic Institute Sensei system. The data were tested for tree
      species classification. The test area was an urban garden in the City of Espoo,
      Finland. Point clouds representing 168 individual tree specimens of 23 tree
      species were determined manually. The classification of the trees was done using
      first only the spatial data from point clouds, then with only the spectral data
      obtained with a spectrometer, and finally with the combined spatial and
      hyperspectral data from both sensors. Two classification tests were performed:
      the separation of coniferous and deciduous trees, and the identification of
      individual tree species. All determined tree specimens were used in
      distinguishing coniferous and deciduous trees. A subset of 133 trees and 10 tree
      species was used in the tree species classification. The best classification
      results for the fused data were 95.8% for the separation of the coniferous and
      deciduous classes. The best overall tree species classification succeeded with
      83.5% accuracy for the best tested fused data feature combination. The respective
      results for paired structural features derived from the laser point cloud were
      90.5% for the separation of the coniferous and deciduous classes and 65.4% for
      the species classification. Classification accuracies with paired hyperspectral
      reflectance value data were 90.5% for the separation of coniferous and deciduous
      classes and 62.4% for different species. The results are among the first of their
      kind and they show that mobile collected fused data outperformed single-sensor
      data in both classification tests and by a significant margin.

PMID- 22163895
TI  - A cross-layer duty cycle MAC protocol supporting a pipeline feature for wireless
      sensor networks.
AB  - Although the conventional duty cycle MAC protocols for Wireless Sensor Networks
      (WSNs) such as RMAC perform well in terms of saving energy and reducing end-to
      end delivery latency, they were designed independently and require an extra
      routing protocol in the network layer to provide path information for the MAC
      layer. In this paper, we propose a new cross-layer duty cycle MAC protocol with
      data forwarding supporting a pipeline feature (P-MAC) for WSNs. P-MAC first
      divides the whole network into many grades around the sink. Each node identifies
      its grade according to its logical hop distance to the sink and simultaneously
      establishes a sleep/wakeup schedule using the grade information. Those nodes in
      the same grade keep the same schedule, which is staggered with the schedule of
      the nodes in the adjacent grade. Then a variation of the RTS/CTS handshake
      mechanism is used to forward data continuously in a pipeline fashion from the
      higher grade to the lower grade nodes and finally to the sink. No extra routing
      overhead is needed, thus increasing the network scalability while maintaining the
      superiority of duty-cycling. The simulation results in OPNET show that P-MAC has
      better performance than S-MAC and RMAC in terms of packet delivery latency and
      energy efficiency.

PMID- 22163896
TI  - Compact electron gun based on secondary emission through ionic bombardment.
AB  - We present a new compact electron gun based on the secondary emission through
      ionic bombardment principle. The driving parameters to develop such a gun are to
      obtain a quite small electron gun for an in-flight instrument performing Electron
      Beam Fluorescence measurements (EBF) on board of a reentry vehicle in the upper
      atmosphere. These measurements are useful to characterize the gas flow around the
      vehicle in terms of gas chemical composition, temperatures and velocity of the
      flow which usually presents thermo-chemical non-equilibrium. Such an instrument
      can also be employed to characterize the upper atmosphere if placed on another
      carrier like a balloon. In ground facilities, it appears as a more practical tool
      to characterize flows in wind tunnel studies or as an alternative to complex
      electron guns in industrial processes requiring an electron beam. We describe in
      this paper the gun which has been developed as well as its different features
      which have been characterized in the laboratory.

PMID- 22163897
TI  - Modeling of beams' multiple-contact mode with an application in the design of a
      high-g threshold microaccelerometer.
AB  - Beam's multiple-contact mode, characterized by multiple and discrete contact
      regions, non-uniform stoppers' heights, irregular contact sequence, seesaw-like
      effect, indirect interaction between different stoppers, and complex coupling
      relationship between loads and deformation is studied. A novel analysis method
      and a novel high speed calculation model are developed for multiple-contact mode
      under mechanical load and electrostatic load, without limitations on stopper
      height and distribution, providing the beam has stepped or curved shape. Accurate
      values of deflection, contact load, contact region and so on are obtained
      directly, with a subsequent validation by CoventorWare. A new concept design of
      high-g threshold microaccelerometer based on multiple-contact mode is presented,
      featuring multiple acceleration thresholds of one sensitive component and
      consequently small sensor size.

PMID- 22163898
TI  - Retrieval of the extreme values under deadline constraints in wireless sensor
      networks.
AB  - We consider a problem of retrieving the extreme value among sensed data under
      deadline constraints in wireless sensor networks with potential applications to
      alarm systems. The sensed data is mapped to a score which we adopt as a unified
      measure of the relative urgency of the data. The objective is to retrieve the
      data with the maximum score. We propose fully distributed schemes for contention
      based medium access and data combining. The proposed medium access scheme uses a
      randomized back-off which is controlled based on the score of the data to be
      transmitted. Data combining techniques are proposed to further suppress
      unnecessary traffic and reduce contention. The key observation is that one should
      aggressively prioritize packets with high score, up to an extent that does not
      incur excessive contention in channel access. Designed to capture such aspect,
      the proposed scheme is shown to substantially decrease the latency of the
      retrieval.

PMID- 22163899
TI  - NCO-sP(EO-stat-PO) coatings on gold sensors--a QCM study of hemocompatibility.
AB  - The reliability of implantable blood sensors is often hampered by unspecific
      adsorption of plasma proteins and blood cells. This not only leads to a loss of
      sensor signal over time, but can also result in undesired host vs. graft
      reactions. Within this study we evaluated the hemocompatibility of isocyanate
      conjugated star shaped polytheylene oxide-polypropylene oxide co-polymers NCO
      sP(EO-stat-PO) when applied to gold surfaces as an auspicious coating material
      for gold sputtered blood contacting sensors. Quartz crystal microbalance (QCM)
      sensors were coated with ultrathin NCO-sP(EO-stat-PO) films and compared with
      uncoated gold sensors. Protein resistance was assessed by QCM measurements with
      fibrinogen solution and platelet poor plasma (PPP), followed by quantification of
      fibrinogen adsorption. Hemocompatibility was tested by incubation with human
      platelet rich plasma (PRP). Thrombin antithrombin-III complex (TAT), beta
      thromboglobulin (beta-TG) and platelet factor 4 (PF4) were used as coagulation
      activation markers. Furthermore, scanning electron microscopy (SEM) was used to
      visualize platelet adhesion to the sensor surfaces. Compared to uncoated gold
      sensors, NCO-sP(EO-stat-PO) coated sensors revealed significant better resistance
      against protein adsorption, lower TAT generation and a lower amount of adherent
      platelets. Moreover, coating with ultrathin NCO-sP(EO-stat-PO) films creates a
      cell resistant hemocompatible surface on gold that increases the chance of
      prolonged sensor functionality and can easily be modified with specific receptor
      molecules.

PMID- 22163900
TI  - FT-IR-cPAS--new photoacoustic measurement technique for analysis of hot gases: a
      case study on VOCs.
AB  - This article describes a new photoacoustic FT-IR system capable of operating at
      elevated temperatures. The key hardware component is an optical-readout
      cantilever microphone that can work up to 200  degrees C. All parts in contact
      with the sample gas were put into a heated oven, incl. the photoacoustic cell.
      The sensitivity of the built photoacoustic system was tested by measuring 18
      different VOCs. At 100 ppm gas concentration, the univariate signal to noise
      ratios (1sigma, measurement time 25.5 min, at highest peak, optical resolution 8
      cm(-1)) of the spectra varied from minimally 19 for o-xylene up to 329 for butyl
      acetate. The sensitivity can be improved by multivariate analyses over broad
      wavelength ranges, which effectively co-adds the univariate sensitivities
      achievable at individual wavelengths. The multivariate limit of detection
      (3sigma, 8.5 min, full useful wavelength range), i.e., the best possible inverse
      analytical sensitivity achievable at optimum calibration, was calculated using
      the SBC method and varied from 2.60 ppm for dichloromethane to 0.33 ppm for butyl
      acetate. Depending on the shape of the spectra, which often only contain a few
      sharp peaks, the multivariate analysis improved the analytical sensitivity by 2.2
      to 9.2 times compared to the univariate case. Selectivity and multi component
      ability were tested by a SBC calibration including 5 VOCs and water. The average
      cross selectivities turned out to be less than 2% and the resulting inverse
      analytical sensitivities of the 5 interfering VOCs was increased by maximum
      factor of 2.2 compared to the single component sensitivities. Water subtraction
      using SBC gave the true analyte concentration with a variation coefficient of 3%,
      although the sample spectra (methyl ethyl ketone, 200 ppm) contained water from
      1,400 to 100k ppm and for subtraction only one water spectra (10k ppm) was used.
      The developed device shows significant improvement to the current state-of-the
      art measurement methods used in industrial VOC measurements.

PMID- 22163902
TI  - Burst packet loss concealment using multiple codebooks and comfort noise for CELP
      type speech coders in wireless sensor networks.
AB  - In this paper, a packet loss concealment (PLC) algorithm for CELP-type speech
      coders is proposed in order to improve the quality of decoded speech under burst
      packet loss conditions in a wireless sensor network. Conventional receiver-based
      PLC algorithms in the G.729 speech codec are usually based on speech correlation
      to reconstruct the decoded speech of lost frames by using parameter information
      obtained from the previous correctly received frames. However, this approach has
      difficulty in reconstructing voice onset signals since the parameters such as
      pitch, linear predictive coding coefficient, and adaptive/fixed codebooks of the
      previous frames are mostly related to silence frames. Thus, in order to
      reconstruct speech signals in the voice onset intervals, we propose a multiple
      codebook-based approach that includes a traditional adaptive codebook and a new
      random codebook composed of comfort noise. The proposed PLC algorithm is designed
      as a PLC algorithm for G.729 and its performance is then compared with that of
      the PLC algorithm currently employed in G.729 via a perceptual evaluation of
      speech quality, a waveform comparison, and a preference test under different
      random and burst packet loss conditions. It is shown from the experiments that
      the proposed PLC algorithm provides significantly better speech quality than the
      PLC algorithm employed in G.729 under all the test conditions.

PMID- 22163901
TI  - Odour detection methods: olfactometry and chemical sensors.
AB  - The complexity of the odours issue arises from the sensory nature of smell. From
      the evolutionary point of view olfaction is one of the oldest senses, allowing
      for seeking food, recognizing danger or communication: human olfaction is a
      protective sense as it allows the detection of potential illnesses or infections
      by taking into account the odour pleasantness/unpleasantness. Odours are mixtures
      of light and small molecules that, coming in contact with various human sensory
      systems, also at very low concentrations in the inhaled air, are able to
      stimulate an anatomical response: the experienced perception is the odour. Odour
      assessment is a key point in some industrial production processes (i.e., food,
      beverages, etc.) and it is acquiring steady importance in unusual technological
      fields (i.e., indoor air quality); this issue mainly concerns the environmental
      impact of various industrial activities (i.e., tanneries, refineries,
      slaughterhouses, distilleries, civil and industrial wastewater treatment plants,
      landfills and composting plants) as sources of olfactory nuisances, the top air
      pollution complaint. Although the human olfactory system is still regarded as the
      most important and effective "analytical instrument" for odour evaluation, the
      demand for more objective analytical methods, along with the discovery of
      materials with chemo-electronic properties, has boosted the development of sensor
      based machine olfaction potentially imitating the biological system. This review
      examines the state of the art of both human and instrumental sensing currently
      used for the detection of odours. The olfactometric techniques employing a panel
      of trained experts are discussed and the strong and weak points of odour
      assessment through human detection are highlighted. The main features and the
      working principles of modern electronic noses (E-Noses) are then described,
      focusing on their better performances for environmental analysis. Odour emission
      monitoring carried out through both the techniques is finally reviewed in order
      to show the complementary responses of human and instrumental sensing.

PMID- 22163903
TI  - A novel cloning template designing method by using an artificial bee colony
      algorithm for edge detection of CNN based imaging sensors.
AB  - Cellular Neural Networks (CNNs) have been widely used recently in applications
      such as edge detection, noise reduction and object detection, which are among the
      main computer imaging processes. They can also be realized as hardware based
      imaging sensors. The fact that hardware CNN models produce robust and effective
      results has attracted the attention of researchers using these structures within
      image sensors. Realization of desired CNN behavior such as edge detection can be
      achieved by correctly setting a cloning template without changing the structure
      of the CNN. To achieve different behaviors effectively, designing a cloning
      template is one of the most important research topics in this field. In this
      study, the edge detecting process that is used as a preliminary process for
      segmentation, identification and coding applications is conducted by using CNN
      structures. In order to design the cloning template of goal-oriented CNN
      architecture, an Artificial Bee Colony (ABC) algorithm which is inspired from the
      foraging behavior of honeybees is used and the performance analysis of ABC for
      this application is examined with multiple runs. The CNN template generated by
      the ABC algorithm is tested by using artificial and real test images. The results
      are subjectively and quantitatively compared with well-known classical edge
      detection methods, and other CNN based edge detector cloning templates available
      in the imaging literature. The results show that the proposed method is more
      successful than other methods.

PMID- 22163905
TI  - FRCA: a fuzzy relevance-based cluster head selection algorithm for wireless
      mobile ad-hoc sensor networks.
AB  - Clustering is an important mechanism that efficiently provides information for
      mobile nodes and improves the processing capacity of routing, bandwidth
      allocation, and resource management and sharing. Clustering algorithms can be
      based on such criteria as the battery power of nodes, mobility, network size,
      distance, speed and direction. Above all, in order to achieve good clustering
      performance, overhead should be minimized, allowing mobile nodes to join and
      leave without perturbing the membership of the cluster while preserving current
      cluster structure as much as possible. This paper proposes a Fuzzy Relevance
      based Cluster head selection Algorithm (FRCA) to solve problems found in existing
      wireless mobile ad hoc sensor networks, such as the node distribution found in
      dynamic properties due to mobility and flat structures and disturbance of the
      cluster formation. The proposed mechanism uses fuzzy relevance to select the
      cluster head for clustering in wireless mobile ad hoc sensor networks. In the
      simulation implemented on the NS-2 simulator, the proposed FRCA is compared with
      algorithms such as the Cluster-based Routing Protocol (CBRP), the Weighted-based
      Adaptive Clustering Algorithm (WACA), and the Scenario-based Clustering Algorithm
      for Mobile ad hoc networks (SCAM). The simulation results showed that the
      proposed FRCA achieves better performance than that of the other existing
      mechanisms.

PMID- 22163904
TI  - Microfabrication and applications of opto-microfluidic sensors.
AB  - A review of research activities on opto-microfluidic sensors carried out by the
      research groups in Canada is presented. After a brief introduction of this
      exciting research field, detailed discussion is focused on different techniques
      for the fabrication of opto-microfluidic sensors, and various applications of
      these devices for bioanalysis, chemical detection, and optical measurement. Our
      current research on femtosecond laser microfabrication of optofluidic devices is
      introduced and some experimental results are elaborated. The research on opto
      microfluidics provides highly sensitive opto-microfluidic sensors for practical
      applications with significant advantages of portability, efficiency, sensitivity,
      versatility, and low cost.

PMID- 22163906
TI  - A new dual-frequency liquid crystal lens with ring-and-pie electrodes and a
      driving scheme to prevent disclination lines and improve recovery time.
AB  - A new liquid crystal lens design is proposed to improve the recovery time with a
      ring-and-pie electrode pattern through a suitable driving scheme and using dual
      frequency liquid crystals (DFLC) MLC-2048. Compared with the conventional single
      hole-type liquid crystal lens, this new structure of the DFLC lens is composed of
      only two ITO glasses, one of which is designed with the ring-and-pie pattern. For
      this device, one can control the orientation of liquid crystal directors via a
      three-stage switching procedure on the particularly-designed ring-and-pie
      electrode pattern. This aims to eliminate the disclination lines, and using
      different drive frequencies to reduce the recovery time to be less than 5
      seconds. The proposed DFLC lens is shown effective in reducing recovery time, and
      then serves well as a potential device in places of the conventional lenses with
      fixed focus lengths and the conventional LC lens with a single circular-hole
      electrode pattern.

PMID- 22163907
TI  - Infrared sensor system for mobile-robot positioning in intelligent spaces.
AB  - The aim of this work was to position a Mobile Robot in an Intelligent Space, and
      this paper presents a sensorial system for measuring differential phase-shifts in
      a sinusoidally modulated infrared signal transmitted from the robot. Differential
      distances were obtained from these phase-shifts, and the position of the robot
      was estimated by hyperbolic trilateration. Due to the extremely severe trade-off
      between SNR, angle (coverage) and real-time response, a very accurate design and
      device selection was required to achieve good precision with wide coverage and
      acceptable robot speed. An I/Q demodulator was used to measure phases with one
      stage synchronous demodulation to DC. A complete set of results from real
      measurements, both for distance and position estimations, is provided to
      demonstrate the validity of the system proposed, comparing it with other similar
      indoor positioning systems.

PMID- 22163908
TI  - A survey on multimedia-based cross-layer optimization in visual sensor networks.
AB  - Visual sensor networks (VSNs) comprised of battery-operated electronic devices
      endowed with low-resolution cameras have expanded the applicability of a series
      of monitoring applications. Those types of sensors are interconnected by ad hoc
      error-prone wireless links, imposing stringent restrictions on available
      bandwidth, end-to-end delay and packet error rates. In such context, multimedia
      coding is required for data compression and error-resilience, also ensuring
      energy preservation over the path(s) toward the sink and improving the end-to-end
      perceptual quality of the received media. Cross-layer optimization may enhance
      the expected efficiency of VSNs applications, disrupting the conventional
      information flow of the protocol layers. When the inner characteristics of the
      multimedia coding techniques are exploited by cross-layer protocols and
      architectures, higher efficiency may be obtained in visual sensor networks. This
      paper surveys recent research on multimedia-based cross-layer optimization,
      presenting the proposed strategies and mechanisms for transmission rate
      adjustment, congestion control, multipath selection, energy preservation and
      error recovery. We note that many multimedia-based cross-layer optimization
      solutions have been proposed in recent years, each one bringing a wealth of
      contributions to visual sensor networks.

PMID- 22163909
TI  - Cognitive facilitation following intentional odor exposure.
AB  - This paper reviews evidence that, in addition to incidental olfactory pollutants,
      intentional odor delivery can impact cognitive operations both positively and
      negatively. Evidence for cognitive facilitation/interference is reviewed
      alongside four potential explanations for odor-induced effects. It is concluded
      that the pharmacological properties of odors can induce changes in cognition.
      However, these effects can be accentuated/attenuated by the shift in mood
      following odor exposure, expectancy of cognitive effects, and cues to behavior
      via the contextual association with the odor. It is proposed that greater
      consideration is required in the intentional utilization of odors within both
      industrial and private locations, since differential effects are observed for
      odors with positive hedonic qualities.

PMID- 22163910
TI  - A large area tactile sensor patch based on commercial force sensors.
AB  - This paper reports the design of a tactile sensor patch to cover large areas of
      robots and machines that interact with human beings. Many devices have been
      proposed to meet such a demand. These realizations are mostly custom-built or
      developed in the lab. The sensor of this paper is implemented with commercial
      force sensors. This has the benefit of a more foreseeable response of the sensor
      if its behavior is understood as the aggregation of readings from all the
      individual force sensors in the array. A few reported large area tactile sensors
      are also based on commercial sensors. However, the one in this paper is the first
      of this kind based on the use of polymeric commercial force sensing resistors
      (FSR) as unit elements of the array or tactels, which results in a robust sensor.
      The paper discusses design issues related to some necessary modifications of the
      force sensor, its assembly in an array, and the signal conditioning. The patch
      has 16 * 9 force sensors mounted on a flexible printed circuit board with a
      spatial resolution of 18.5 mm. The force range of a tactel is 6 N and its
      sensitivity is 0.6 V/N. The array is read at a rate of 78 frames per second.
      Finally, two simple application examples are also carried out with the sensor
      mounted on the forearm of a rescue robot that communicates with the sensor
      through a CAN bus.

PMID- 22163911
TI  - Design and analysis of a differential waveguide structure to improve
      magnetostrictive linear position sensors.
AB  - Magnetostrictive linear position sensors (MLPS) are high-precision sensors used
      in the industrial field for measuring the propagation time of ultrasonic signals
      in a waveguide. To date, MLPS have attracted widespread attention for their
      accuracy, reliability, and cost-efficiency in performing non-contact, multiple
      measurements. However, the sensor, with its traditional structure, is susceptible
      to electromagnetic interference, which affects accuracy. In the present study, we
      propose a novel structure of MLPS that relies on two differential waveguides to
      improve the signal-to-noise ratio, common-mode rejection ratio, and accuracy of
      MLPS. The proposed sensor model can depict sensor performance and the
      relationship of sensor parameters. Experimental results with the new sensor
      indicate that the new structure can improve accuracy to +/-0.1 mm higher than +/
      0.2 mm with a traditional structure. In addition, the proposed sensor shows a
      considerable improvement in temperature characteristics.

PMID- 22163912
TI  - Odor removal characteristics of a laminated film-electrode packed-bed nonthermal
      plasma reactor.
AB  - Odor control has gained importance for ensuring a comfortable living environment.
      In this paper, the authors report the experimental results of a study on the
      detailed characteristics of a laminated film-electrode and a laminated film
      electrode packed-bed nonthermal plasma reactor, which are types of dielectric
      barrier discharge (DBD) reactor used for odor control. These plasma reactors can
      be potentially used for the decomposition of volatile organic compounds (VOCs)
      and reduction of NO(x). The reactor is driven by a low-cost 60-Hz neon
      transformer. Removal efficiencies under various experimental conditions are
      studied. The complete decomposition of the main odor component, namely, NH(3), is
      achieved in a dry environment. The retention times are investigated for the
      complete removal of NH(3) in the case of the film-electrode plasma reactor and
      the film-electrode packed-bed plasma reactor. The removal efficiency of the
      former reactor is lower than that of the latter reactor. Mixing another odor
      component such as CH(3)CHO in the gas stream has no significant effect on NH(3)
      removal efficiency.

PMID- 22163913
TI  - Sensing the structural differences in cellulose from apple and bacterial cell
      wall materials by Raman and FT-IR spectroscopy.
AB  - Raman and Fourier Transform Infrared (FT-IR) spectroscopy was used for assessment
      of structural differences of celluloses of various origins. Investigated
      celluloses were: bacterial celluloses cultured in presence of pectin and/or
      xyloglucan, as well as commercial celluloses and cellulose extracted from apple
      parenchyma. FT-IR spectra were used to estimate of the I(beta) content, whereas
      Raman spectra were used to evaluate the degree of crystallinity of the cellulose.
      The crystallinity index (X(C)(RAMAN)%) varied from -25% for apple cellulose to
      53% for microcrystalline commercial cellulose. Considering bacterial cellulose,
      addition of xyloglucan has an impact on the percentage content of cellulose
      I(beta). However, addition of only xyloglucan or only pectins to pure bacterial
      cellulose both resulted in a slight decrease of crystallinity. However, culturing
      bacterial cellulose in the presence of mixtures of xyloglucan and pectins results
      in an increase of crystallinity. The results confirmed that the higher degree of
      crystallinity, the broader the peak around 913 cm(-1). Among all bacterial
      celluloses the bacterial cellulose cultured in presence of xyloglucan and pectin
      (BCPX) has the most similar structure to those observed in natural primary cell
      walls.

PMID- 22163914
TI  - Wearable and implantable wireless sensor network solutions for healthcare
      monitoring.
AB  - Wireless sensor network (WSN) technologies are considered one of the key research
      areas in computer science and the healthcare application industries for improving
      the quality of life. The purpose of this paper is to provide a snapshot of
      current developments and future direction of research on wearable and implantable
      body area network systems for continuous monitoring of patients. This paper
      explains the important role of body sensor networks in medicine to minimize the
      need for caregivers and help the chronically ill and elderly people live an
      independent life, besides providing people with quality care. The paper provides
      several examples of state of the art technology together with the design
      considerations like unobtrusiveness, scalability, energy efficiency, security and
      also provides a comprehensive analysis of the various benefits and drawbacks of
      these systems. Although offering significant benefits, the field of wearable and
      implantable body sensor networks still faces major challenges and open research
      problems which are investigated and covered, along with some proposed solutions,
      in this paper.

PMID- 22163915
TI  - Roughness encoding in human and biomimetic artificial touch: spatiotemporal
      frequency modulation and structural anisotropy of fingerprints.
AB  - The influence of fingerprints and their curvature in tactile sensing performance
      is investigated by comparative analysis of different design parameters in a
      biomimetic artificial fingertip, having straight or curved fingerprints. The
      strength in the encoding of the principal spatial period of ridged tactile
      stimuli (gratings) is evaluated by indenting and sliding the surfaces at
      controlled normal contact force and tangential sliding velocity, as a function of
      fingertip rotation along the indentation axis. Curved fingerprints guaranteed
      higher directional isotropy than straight fingerprints in the encoding of the
      principal frequency resulting from the ratio between the sliding velocity and the
      spatial periodicity of the grating. In parallel, human microneurography
      experiments were performed and a selection of results is included in this work in
      order to support the significance of the biorobotic study with the artificial
      tactile system.

PMID- 22163916
TI  - Label-free electrochemical detection of the specific oligonucleotide sequence of
      dengue virus type 1 on pencil graphite electrodes.
AB  - A biosensor that relies on the adsorption immobilization of the 18-mer single
      stranded nucleic acid related to dengue virus gene 1 on activated pencil graphite
      was developed. Hybridization between the probe and its complementary
      oligonucleotides (the target) was investigated by monitoring guanine oxidation by
      differential pulse voltammetry (DPV). The pencil graphite electrode was made of
      ordinary pencil lead (type 4B). The polished surface of the working electrode was
      activated by applying a potential of 1.8 V for 5 min. Afterward, the dengue
      oligonucleotides probe was immobilized on the activated electrode by applying 0.5
      V to the electrode in 0.5 M acetate buffer (pH 5.0) for 5 min. The hybridization
      process was carried out by incubating at the annealing temperature of the
      oligonucleotides. A time of five minutes and concentration of 1 MUM were found to
      be the optimal conditions for probe immobilization. The electrochemical detection
      of annealing between the DNA probe (TS-1P) immobilized on the modified electrode,
      and the target (TS-1T) was achieved. The target could be quantified in a range
      from 1 to 40 nM with good linearity and a detection limit of 0.92 nM. The
      specificity of the electrochemical biosensor was tested using non-complementary
      sequences of dengue virus 2 and 3.

PMID- 22163917
TI  - A simple method to improve autonomous GPS positioning for tractors.
AB  - Error is always present in the GPS guidance of a tractor along a desired
      trajectory. One way to reduce GPS guidance error is by improving the tractor
      positioning. The most commonly used ways to do this are either by employing more
      precise GPS receivers and differential corrections or by employing GPS together
      with some other local positioning systems such as electronic compasses or
      Inertial Navigation Systems (INS). However, both are complex and expensive
      solutions. In contrast, this article presents a simple and low cost method to
      improve tractor positioning when only a GPS receiver is used as the positioning
      sensor. The method is based on placing the GPS receiver ahead of the tractor, and
      on applying kinematic laws of tractor movement, or a geometric approximation, to
      obtain the midpoint position and orientation of the tractor rear axle more
      precisely. This precision improvement is produced by the fusion of the GPS data
      with tractor kinematic control laws. Our results reveal that the proposed method
      effectively reduces the guidance GPS error along a straight trajectory.

PMID- 22163918
TI  - A cabled acoustic telemetry system for detecting and tracking juvenile salmon:
      part 1. Engineering design and instrumentation.
AB  - In 2001 the U.S. Army Corps of Engineers, Portland District (OR, USA), started
      developing the Juvenile Salmon Acoustic Telemetry System, a nonproprietary
      sensing technology, to meet the needs for monitoring the survival of juvenile
      salmonids through eight large hydroelectric facilities within the Federal
      Columbia River Power System (FCRPS). Initial development focused on coded
      acoustic microtransmitters and autonomous receivers that could be deployed in
      open reaches of the river for detection of the juvenile salmonids implanted with
      microtransmitters as they passed the autonomous receiver arrays. In 2006, the
      Pacific Northwest National Laboratory began the development of an acoustic
      receiver system for deployment at hydropower facilities (cabled receiver) for
      detecting fish tagged with microtransmitters as well as tracking them in two or
      three dimensions for determining route of passage and behavior as the fish passed
      at the facility. The additional information on route of passage, combined with
      survival estimates, is used by the dam operators and managers to make structural
      and operational changes at the hydropower facilities to improve survival of fish
      as they pass the facilities through the FCRPS.

PMID- 22163919
TI  - A cabled acoustic telemetry system for detecting and tracking juvenile salmon:
      part 2. Three-dimensional tracking and passage outcomes.
AB  - In Part 1 of this paper, we presented the engineering design and instrumentation
      of the Juvenile Salmon Acoustic Telemetry System (JSATS) cabled system, a
      nonproprietary sensing technology developed by the U.S. Army Corps of Engineers,
      Portland District (Oregon, USA) to meet the needs for monitoring the survival of
      juvenile salmonids through the hydroelectric facilities within the Federal
      Columbia River Power System. Here in Part 2, we describe how the JSATS cabled
      system was employed as a reference sensor network for detecting and tracking
      juvenile salmon. Time-of-arrival data for valid detections on four hydrophones
      were used to solve for the three-dimensional (3D) position of fish surgically
      implanted with JSATS acoustic transmitters. Validation tests demonstrated high
      accuracy of 3D tracking up to 100 m upstream from the John Day Dam spillway. The
      along-dam component, used for assigning the route of fish passage, had the
      highest accuracy; the median errors ranged from 0.02 to 0.22 m, and root mean
      square errors ranged from 0.07 to 0.56 m at distances up to 100 m. For the 2008
      case study at John Day Dam, the range for 3D tracking was more than 100 m
      upstream of the dam face where hydrophones were deployed, and detection and
      tracking probabilities of fish tagged with JSATS acoustic transmitters were
      higher than 98%. JSATS cabled systems have been successfully deployed on several
      major dams to acquire information for salmon protection and for development of
      more "fish-friendly" hydroelectric facilities.

PMID- 22163920
TI  - Assessment of Acacia koa forest health across environmental gradients in Hawai'i
      using fine resolution remote sensing and GIS.
AB  - Koa (Acacia koa) forests are found across broad environmental gradients in the
      Hawai'ian Islands. Previous studies have identified koa forest health problems
      and dieback at the plot level, but landscape level patterns remain unstudied. The
      availability of high-resolution satellite images from the new GeoEye1 satellite
      offers the opportunity to conduct landscape-level assessments of forest health.
      The goal of this study was to develop integrated remote sensing and geographic
      information systems (GIS) methodologies to characterize the health of koa forests
      and model the spatial distribution and variability of koa forest dieback patterns
      across an elevation range of 600-1,000 m asl in the island of Kaua'i, which
      correspond to gradients of temperature and rainfall ranging from 17-20  degrees C
      mean annual temperature and 750-1,500 mm mean annual precipitation. GeoEye1
      satellite imagery of koa stands was analyzed using supervised classification
      techniques based on the analysis of 0.5-m pixel multispectral bands. There was
      clear differentiation of native koa forest from areas dominated by introduced
      tree species and differentiation of healthy koa stands from those exhibiting
      dieback symptoms. The area ratio of healthy koa to koa dieback corresponded
      linearly to changes in temperature across the environmental gradient, with koa
      dieback at higher relative abundance in warmer areas. A landscape-scale map of
      healthy koa forest and dieback distribution demonstrated both the general trend
      with elevation and the small-scale heterogeneity that exists within particular
      elevations. The application of these classification techniques with fine spatial
      resolution imagery can improve the accuracy of koa forest inventory and mapping
      across the islands of Hawai'i. Such findings should also improve ecological
      restoration, conservation and silviculture of this important native tree species.

PMID- 22163921
TI  - Information theory filters for wavelet packet coefficient selection with
      application to corrosion type identification from acoustic emission signals.
AB  - The damage caused by corrosion in chemical process installations can lead to
      unexpected plant shutdowns and the leakage of potentially toxic chemicals into
      the environment. When subjected to corrosion, structural changes in the material
      occur, leading to energy releases as acoustic waves. This acoustic activity can
      in turn be used for corrosion monitoring, and even for predicting the type of
      corrosion. Here we apply wavelet packet decomposition to extract features from
      acoustic emission signals. We then use the extracted wavelet packet coefficients
      for distinguishing between the most important types of corrosion processes in the
      chemical process industry: uniform corrosion, pitting and stress corrosion
      cracking. The local discriminant basis selection algorithm can be considered as a
      standard for the selection of the most discriminative wavelet coefficients.
      However, it does not take the statistical dependencies between wavelet
      coefficients into account. We show that, when these dependencies are ignored, a
      lower accuracy is obtained in predicting the corrosion type. We compare several
      mutual information filters to take these dependencies into account in order to
      arrive at a more accurate prediction.

PMID- 22163922
TI  - Using acoustic sensors to improve the efficiency of the forest value chain in
      Canada: a case study with laminated veneer lumber.
AB  - Engineered wood products for structural use must meet minimum strength and
      stiffness criteria. This represents a major challenge for the industry as the
      mechanical properties of the wood resource are inherently variable. We report on
      a case study that was conducted in a laminated veneer lumber (LVL) mill in order
      to test the potential of an acoustic sensor to predict structural properties of
      the wood resource prior to processing. A population of 266 recently harvested
      aspen logs were segregated into three sub-populations based on measurements of
      longitudinal acoustic speed in wood using a hand tool equipped with a resonance
      based acoustic sensor. Each of the three sub-populations were peeled into veneer
      sheets and graded for stiffness with an ultrasonic device. The average ultrasonic
      propagation time (UPT) of each subpopulation was 418, 440 and 453 microseconds
      for the green, blue, and red populations, respectively. This resulted in
      contrasting proportions of structural veneer grades, indicating that the
      efficiency of the forest value chain could be improved using acoustic sensors. A
      linear regression analysis also showed that the dynamic modulus of elasticity
      (MOE) of LVL was strongly related to static MOE (R(2) = 0.83), which suggests
      that acoustic tools may be used for quality control during the production
      process.